PMID- 14566998
TI  - Changes in treatment strategies for acute otitis media after full implementation
      of the pneumococcal seven valent conjugate vaccine.
AB  - BACKGROUND: Administration of the pneumococcal seven valent conjugate vaccine
      (PCV-7) results in significant reductions in the incidence of invasive
      pneumococcal disease and nasopharyngeal colonization rates; however, the
      reduction in the overall incidence of acute otitis media (AOM) is minimal.
      Despite an ongoing shortage of PCV-7 in the United States, during which children
      are receiving fewer doses at longer intervals than the recommended dosing
      schedule, the incidence of invasive pneumococcal disease in young children has
      continued to decrease. PURPOSE: The purpose of this article is to review why the
      reported effect of PCV-7 on AOM infection rates does not match the reduction in
      invasive pneumococcal disease or the reduction in nasopharyngeal carriage of
      Streptococcus pneumoniae. METHODS: The potential effect of a fully implemented
      PCV-7 schedule on AOM infections is calculated based on serotype-specific AOM
      reduction rates observed in clinical studies. Clinical success rates of various
      antimicrobials used in the treatment of AOM in children fully immunized with PCV
      7 also are calculated based on projected PCV-7-induced changes in pathogen
      profiles and documented antimicrobial resistance rates. Questions regarding
      potential serotype substitution in children with AOM but not invasive
      pneumococcal disease, the increased incidence of infection with Haemophilus
      influenzae in children immunized with PCV-7 and the possibility of herd immunity
      also will be addressed. RESULTS: Although the majority of penicillin
      nonsusceptible S. pneumoniae are included in PCV-7, AOM caused by these strains
      will not completely disappear, especially in children 24 months of age and
      younger. CONCLUSIONS: Consequently, clinicians must continue to consider
      penicillin-nonsusceptible pneumococci when prescribing antimicrobials for AOM.

PMID- 14566999
TI  - Macrolide resistance: an increasing concern for treatment failure in children.
AB  - BACKGROUND: Antimicrobial treatment of pediatric respiratory tract infections has
      evolved during the past 30 years as a result of antimicrobial resistance. The
      focus of antimicrobial therapy in these conditions has shifted from penicillins
      to other agents because of the dramatic increase in antimicrobial resistance
      among common respiratory pathogens, including Streptococcus pneumoniae,
      Haemophilus influenzae and Moraxella catarrhalis. It is important for clinicians
      to understand how resistance develops so that they can help prevent this
      phenomenon from occurring with other antimicrobials. METHODS: This article
      reviews the published literature on resistance to macrolide antimicrobials among
      common pediatric respiratory tract pathogens and clinical and bacteriologic
      outcomes of infections with these pathogens. RESULTS: Resistance among common
      pediatric respiratory tract pathogens to macrolides occurs through two main
      mechanisms, alteration of the target site and active efflux. Although resistance
      patterns vary by geographic region, the widespread use of macrolides has
      contributed to the emergence of both types of macrolide-resistant organisms.
      Conditions that favor the selection and proliferation of resistant strains
      include children with repeated, close contact who frequently receive
      antimicrobial treatment or prophylaxis, such as children who attend day care.
      Recent US surveillance data show that 20 to 30% of S. pneumoniae are resistant to
      macrolides, with approximately two-thirds of macrolide-resistant strains
      associated with an efflux mechanism and the remainder associated with a ribosomal
      methylase. Additionally, although less well-known, virtually all strains of H.
      influenzae have an intrinsic macrolide efflux pump. As resistance to macrolides
      has increased, clinical failures have resulted, and these agents are no longer
      considered appropriate for empiric first line antimicrobial therapy of acute
      otitis media and sinusitis unless patients are truly penicillin-allergic.
      Therefore, other antimicrobials are recommended for the empiric treatment of
      children with respiratory tract infections, including higher doses of amoxicillin
      and amoxicillin/clavulanate (90 mg/kg/day amoxicillin), cefuroxime axetil and
      intramuscular ceftriaxone. CONCLUSIONS: As resistance to macrolides increases and
      clinical failures in children become more common with this class of
      antimicrobials, judicious use of antimicrobials is needed. This includes limiting
      antimicrobial use for viral infections and using the most effective agents when
      antimicrobials are clinically indicated, such as higher doses of amoxicillin and
      amoxicillin/clavulanate. Application of these principles may prevent
      proliferation and further development of resistance.

PMID- 14567000
TI  - Amoxicillin/clavulanate for infections in infants and children: past, present and
      future.
AB  - Chemical synthesis of the penicillin nucleus in the 1950s made introduction of a
      broad array of new and important antimicrobials, including ampicillin and
      amoxicillin, possible. Ampicillin was introduced in 1962 in oral and parenteral
      forms as the first of the semisynthetic penicillins to provide increased activity
      against Gram-negative bacteria. Amoxicillin replaced oral ampicillin beginning in
      1974 because amoxicillin resulted in higher and more prolonged serum
      concentrations than did equivalent doses of ampicillin. Amoxicillin/clavulanate
      (Augmentin) was introduced in the United States in 1984 to enhance the activity
      of amoxicillin by addition of the beta-lactamase inhibitor, clavulanic acid.
      During the past 20 years, amoxicillin/clavulanate has proven effective for a
      variety of pediatric infectious diseases, particularly acute otitis media (AOM).
      In 2001, a new pediatric formulation, high dose amoxicillin/clavulanate
      (Augmentin ES-600) was approved for use in the United States. The high dose
      preparation addressed the needs of pediatricians by providing greater amounts of
      amoxicillin while maintaining the same daily dose of clavulanic acid as the
      regular strength formulation. Doubling the dose of amoxicillin for management of
      recurrent and persistent AOM was recommended in 1999 by the Centers for Disease
      Control and Prevention because of concern about the increased incidence of
      nonsusceptible strains of Streptococcus pneumoniae. The original formulation
      combined amoxicillin/clavulanate in a 4:1 ratio and was followed by a 7:1 ratio
      formulation. The high dose formulation (600 mg of amoxicillin per 5 ml) provides
      a 14:1 ratio of amoxicillin to clavulanate. Although management of AOM will
      likely undergo changes in the coming years, amoxicillin is expected to remain
      first line therapy for AOM. For children who fail initial therapy with
      amoxicillin, high dose amoxicillin/clavulanate, an oral cephalosporin or
      parenteral ceftriaxone is recommended.

PMID- 14567001
TI  - Sexual function and the older woman.
AB  - The most important aspect to consider in optimizing the sexual health of the
      older woman is to ask about it, and determine what might be contributing to any
      difficulties that are faced. It also behooves all health providers to remind
      older women (and older men) that age is not a barrier to sexually transmitted
      diseases. Recognition that healthy sexuality is an important issue for achieving
      quality of life is an area that patients and their providers need to be cognizant
      of, but one where far more research and evaluation need to occur.

PMID- 14567002
TI  - Disorders of male sexual function.
AB  - Sexuality remains an important issue in the older population. In spite of a
      decreased ability to achieve an erection, there is continued sexual desire. Many
      studies suggest that erectile dysfunction in the aged is primarily caused by age
      associated chronic disease rather than normal, healthy aging. Therefore,
      preventive measures that are aimed at the underlying diseases should be sought.
      Nevertheless, effective treatment options are now available to successfully
      regain sexual function and thereby, improve quality of life.

PMID- 14567003
TI  - Menopause.
AB  - Elevating women from the nadir of ovarian hypofunction has been a major driving
      force in developing hormonal strategies for the management of menopause. As
      indicated by recent evidence, however, this may have resulted in unacceptable
      morbidity in several women. Likewise, the use of menstrual cessation as the
      hallmark of menopause may have served the counterproductive effect of delaying
      the onset of appropriate preventive pharmacologic and non-pharmacologic
      strategies until the later years of life. Preventive and therapeutic strategies
      that target the menopausal phase of life exclusively are grossly inadequate.
      Unquestionably, the controversies that surround the precise health implications
      of menopause deal mainly with the risk of chronic disease. Health professionals
      are best advised to develop menopausal intervention strategies that parallel the
      continuum of a woman's life, beginning in adolescence and extending into later
      life. Preventive screening includes the following: History Relevant medical
      history Develop risk profile of chronic diseases (e.g., cardiovascular disease,
      cancer, osteoporosis) Dietary history Sexual history Physical exercise history
      Medication history Physical examination Body mass index evaluation Breast
      examination and instruction in examination technique Bimanual pelvic examination
      Nutritional assessment Investigation Cholesterol levels Stool for occult blood
      Thyroid function tests Papanicolaou smears HIV testing if positive risk factors
      Psychosocial evaluation Family relationships Job satisfaction Sexuality High-risk
      social behaviors Review perception of self-health Annual health examination is
      encouraged in all perimenopausal women. Additionally, preventive screening should
      be instituted, as appropriate, in all women of reproductive age.

PMID- 14567004
TI  - Andropause: an old concept in new clothing.
AB  - There is increasing evidence that the common condition of hypogonadism in older
      men when associated with symptoms responds well to testosterone replacement. Over
      the last few years there has been a marked increase in the awareness and
      treatment of the andropause [137]. Long-term side effects of testosterone are
      uncertain with only eight people over 50 years having been studied for 10 years
      [138]. Testosterone needs to be considered a quality-of-life drug, similar to
      sildenafil, and at present it should be used only if it produces symptomatic
      improvement. There is a need for a men's health study to determine the long-term
      efficacy and safety of testosterone replacement in older persons.

PMID- 14567005
TI  - Erectile dysfunction: an overview.
AB  - The treatment of male sexual dysfunction in the elderly offers special
      challenges. Commonly, these men have other conditions requiring medical treatment
      and the possibility of adverse drug interactions is common. Similarly, the
      severity of dysfunction is frequently increased by alteration in various organ
      systems. For instance, ED is commonly associated with significant cardiovascular
      problems and hormonal alterations. The treatment of these men requires
      familiarity with the various options available and good clinical judgment to
      determine when and how modification of therapeutic regimens and combinations of
      specific drugs may provide the best responses. Frequently one hears the
      embarrassed older man coming for a consultation and stating that, "At my age, I
      should not be thinking of this." It is imperative to remember that advancing age
      does not preclude sexual interest and desire for performance. A well-informed,
      understanding physician can provide sound advice, institute appropriate
      therapies, and organize intelligent referrals.

PMID- 14567006
TI  - Erectile dysfunction: etiology and treatment in young and old patients.
AB  - This study shows that endocrine and vascular etiologies of erectile dysfunction
      are more common in the older age group, whereas depression and marital discord
      are more common in the younger age group. There is considerable overlap between
      various factors pointing to the multifactorial nature of erectile dysfunction.
      Review of the treatment option chosen reveals that the invasive modalities were
      least common as compared with the popular vacuum tumescence device (although
      cumbersome) and testosterone replacement. Persons with low testosterone have an
      improved efficacy of sildenafil when hypogonadism is treated. Sildenafil with its
      ease of administration and high efficacy seems to be the logical first choice for
      most of the patients. If contraindications exist or treatment failures occur,
      other treatment options should be offered to patients.

PMID- 14567007
TI  - Medications and sexual function.
AB  - There seems to be a reluctance to self-report sexual dysfunction during clinical
      interviews. The rate of reported sexual dysfunction increases when information is
      sought aggressively in the clinical interview. The relationship to a specific
      therapeutic agent, however, can be clouded by the patient's perception and
      coexisting morbidity. Most of the data relating sexual dysfunction to specific
      drugs are anecdotal. The strongest proof of a casual effect is improvement in
      sexual function after withdrawal of the medication. Most of the adverse sexual
      effects of commonly used medications can be predicted from a simplified
      understanding of the human sexual response and physiologic mediators. Alternative
      therapeutic agents can be substituted by understanding these physiologic
      mechanisms and a careful clinical interview. Although polypharmacy is a problem
      for older persons, in some cases sildenafil can be used to correct drug-induced
      impotence.

PMID- 14567008
TI  - Sexuality and disease.
AB  - Disease is commonly associated with sexual dysfunction in both men and women. In
      many cases, effective treatments are available that can improve libido, erectile
      dysfunction, and vaginal dryness. Sexual problems in older persons with disease
      often lead to anxiety, marital discord, and withdrawal. It is the responsibility
      of all health care professionals to inquire about sexuality in all patients, no
      matter what the patient's age, and to be aware that frailty [79-81] is not, in
      itself, a barrier to sexuality. Health professionals need to give education,
      support, and counseling on sexuality for patients with disease.

PMID- 14567009
TI  - Sex and the nursing home.
AB  - Despite the known benefits of continued sexual activity on physical, mental, and
      emotional health, the nursing home resident continues to be sexually invisible.
      There are so few opportunities where the quality of life can be enhanced so
      greatly by so basic interventions. Sexuality in the nursing home is one of them.
      Failure of society to come to grips with the sexual needs of the elderly
      essentially robs them of a fundamental element of self-worth.

PMID- 14567010
TI  - The older homosexual: current concepts of lesbian, gay, bisexual, and transgender
      older Americans.
AB  - Lesbian, gay, bisexual, and transgender older adults require a comprehensive
      medical, behavioral, mental health, and social support evaluation as do all
      elders. Open communication and minimizing barriers in both the patient-provider
      relationship and throughout the continuum of care settings offer a safe
      environment for current and future care. Special attention should be given to
      ensure proper knowledge of social support systems including durable power of
      attorneys, housing and financial planning, and community services available.

PMID- 14567011
TI  - Testosterone and behavior.
AB  - In older men and women testosterone clearly improves libido and perhaps sexual
      activity. A number of authors have tried to describe a set of behavioral symptoms
      associated with the andropause. In older women testosterone seems to decrease
      dysphoria. In men the effects of testosterone on mood are less clear. In older
      men testosterone enhances spatial memory and possibly verbal and working memory.
      Table 2 summarizes the putative behavioral effects of testosterone. [Table: see
      text] There is a clear need for better designed large-scale behavioral studies to
      determine the effects of testosterone in older men and women.

PMID- 14567012
TI  - The use of estrogen in older women.
AB  - The menopause is associated with a relatively abrupt decline in the ovarian
      production of estrogen that results in a state of estrogen deficiency. This
      estrogen deficiency state is associated with an accelerated expression of
      cardiovascular disease, osteoporosis, urogenital atrophy, dermal aging, an
      increased expression of colorectal cancer, an alteration in the expression of
      breast cancer that results in more malignant forms of the disease, and the loss
      of neurons from the brain that is associated with a more rapid decline in
      cognitive function, balance, and an earlier expression of Alzheimer's disease.
      Macular degeneration and cataract formation may be additional consequences of the
      estrogen deficiency state. Thus the estrogen deficiency state may be
      characterized as a state of accelerated aging. The abrupt transition from the
      reproductive state of multiple estrogen-dependent neural systems within the brain
      may affect their function as manifested by the typical menopausal symptoms of hot
      flashes, mood changes, sleep disturbance, and cognitive impairment. This
      transition may trigger a cascade of events that contributes to the acceleration
      of brain aging and the expression of neurodegenerative processes as Alzheimer's
      disease. This article discusses the use of estrogen to prevent these age-related
      changes.

PMID- 14567013
TI  - Paraphilia and aging.
AB  - There is very little professional information on paraphilia and aging in the
      literature. Much of the literature also is dated. This article explores
      paraphilias, sexual excitement, and fetishes, and their relationship in the aging
      population.

PMID- 14567014
TI  - Sexually transmitted diseases.
AB  - Traditionally, STD is considered a disease of younger adults, and older adults
      continue to present a challenge to health care providers. Geriatric health care
      professionals must offer older adults adequate information relating to sexuality
      and aging. In addition, sexual health must be evaluated as a standard domain in
      routine comprehensive geriatric evaluation and management. Large-scale community
      education programs are helpful in encouraging cultural and societal acceptance of
      the sexuality of older adults. Finally, as baby-boomers age, health care
      professionals will face increasing pressure from their patients to address sexual
      health problems in geriatric clinical practice. The current dearth of relevant
      evidence-based information highlights the urgent need for prioritized research in
      this area.

PMID- 14567015
TI  - Management of peritoneal surface malignancy. Preface.

PMID- 14567016
TI  - A historical perspective on colorectal liver metastases and peritoneal
      carcinomatosis: similar results, different treatments.
AB  - Similarities between peritoneal carcinomatosis and liver secondaries allow the
      oncologist to regard the peritoneum as an intraabdominal structure that can, like
      the liver, be resected with curative intent when disseminated disease has
      occurred. The possibility for cure of peritoneal carcinomatosis by cytoreductive
      surgery and IPHC must now be recognized. However, convincing data from controlled
      studies will be required for rapid general acceptance of this treatment,
      bringing, as a consequence, a chance of cure to a larger number of patients with
      a desperate prognosis. This fact, together with a scarcity of patients with
      peritoneal carcinomatosis eligible for definitive treatment, emphasizes the need
      for cooperative studies between centers of reference.

PMID- 14567017
TI  - Treatment and prevention of peritoneal carcinomatosis from colorectal cancer.
AB  - PC from colorectal cancer is a terminal illness for which intravenous
      chemotherapy is the current standard treatment. However, a recent Dutch
      randomized study established the efficacy of maximal cytoreductive surgery plus
      IPCH to achieve statistically significant prolonged survival of these patients.
      In the near future, improvements of IPCH techniques and progress in selecting
      patients by radiologic imaging, by molecular biologic studies or further
      refinement of quantitative prognostic indicators will permit better results.
      Prospective studies must be conducted in the prevention of carcinomatosis in well
      defined high-risk patients.

PMID- 14567018
TI  - Management of peritoneal surface component of ovarian cancer.
AB  - Primary surgery followed by systemic platinum-based chemotherapy is the
      cornerstone of management for ovarian cancer. However, the majority of patients
      have an advanced disease (stage III/IV) at the time of diagnosis rendering the
      optimal primary cytoreduction feasible in only a small percentage of cases. A
      large tumor bulk limits the success of subsequent antiblastic therapy. There are
      two alternatives to overcome this unfavorable situation: (1) employment of ultra
      radical interventions such as peritonectomy procedures, to increase the optimal
      cytoreduction rate; or (2) neoadjuvant chemotherapy. Whether such strategies
      would have an influence on the final outcome of patients is an issue to be
      defined in further prospective randomized studies. For second-line therapies no
      consensus regarding treatment has emerged. When previous effective drug
      combinations fail, there is virtually no chance of inducing a significant
      response with second-line treatment. The combination of secondary CRS and
      intraperitoneal hyperthermic perfusion constitutes a feasible and potential
      option for this subset of patients based on phase II studies. A randomized trial
      will be conducted to test the effectiveness of this strategy in patients with
      cisplatin-resistant disease. The indication for second-line treatment is
      macroscopic residual or relapse within 6 months after the completion of first
      line chemotherapy.

PMID- 14567019
TI  - The etiology, clinical presentation, and management of pseudomyxoma peritonei.
AB  - PMP is a rare condition, which, although of "borderline malignancy," is
      invariably fatal. Difficulties exist with the definition of PMP. It has been
      broadly applied to include a heterogenous group of pathologic lesions that
      present clinically with "jelly belly" due to mucinous ascites. The relatively few
      reports in the literature commonly use different pathologic definitions, and
      there is no consensus on the point of separation between PMP and carcinomatosis
      secondary to a mucinous adenocarcinoma. Sugarbaker has suggested "the term
      pseudomyxoma peritonei syndrome be strictly applied to a pathologically and
      prognostically homogenous group of cases characterized by histologically benign
      peritoneal tumors that are frequently associated with an appendiceal mucinous
      adenoma." This definition excludes all cases with mucinous adenocarcinoma. The
      optimal treatment is undoubtedly complete tumor excision, by complex surgical
      peritonectomy procedures, taking on average 10 hours. Surgery is usually combined
      with intraperitoneal, and now intraoperative heated chemotherapy. These
      techniques have a high morbidity and mortality. The rarity of the condition,
      together with the risks associated with definitive treatment, suggests that such
      treatment ought to be centralized in a few centers, covering a large population.
      The search continues for safer, less aggressive treatments, but is hampered by a
      lack of hard evidence and the absence of experimental animal or human models to
      evaluate emerging strategies.

PMID- 14567020
TI  - A review of peritoneal mesothelioma at the Washington Cancer Institute.
AB  - This article reviews a single institution's experience with 68 patients (21
      females, 47 males) prospectively treated over the last 2 decades with an
      aggressive local-regional approach, combining maximal cytoreductive surgery with
      heated intraoperative intraperitoneal chemotherapy and early postoperative
      intraperitoneal chemotherapy. This multimodality treatment has resulted in a
      median survival of 67 months. Female patients had a significantly better
      prognosis than males. The other significant predictive factors of survival were:
      age, diagnosis by incidental findings, tumor extent, pathology, and completeness
      of cytoreduction.

PMID- 14567021
TI  - Impact of perioperative intraperitoneal chemotherapy on the treatment of primary
      gastric cancer.
AB  - Perioperative intraperitoneal chemotherapy provides effective prevention of
      peritoneal recurrence after resection in advanced gastric cancer, especially in
      gastric cancer with serosal invasion. With improved local-regional control,
      improved survival rate for advanced gastric cancer is achieved. This type of
      regional chemotherapy is an independent treatment-related prognostic factor for
      advanced gastric cancer. There are several methods of perioperative
      intraperitoneal chemotherapy. Among them, early postoperative intraperitoneal
      chemotherapy is simple and easy to perform.

PMID- 14567022
TI  - Effective therapy for peritoneal dissemination in gastric cancer.
AB  - Peritoneal dissemination is the most frequent cause of death from gastric cancer,
      accounting for death in 20% to 40% of patients. Preoperative intraperitoneal
      chemotherapy, peritonectomy, intraoperative chemohyperthermic perfusion, and
      early postoperative intraperitoneal chemotherapy are treatment modalities
      specifically designed to eliminate peritoneal dissemination and progression.
      Preoperative intraperitoneal chemotherapy is for containment of peritoneal free
      cancer cells, and also may facilitate complete eradication of visible peritoneal
      dissemination by peritonectomy. Further, complete cytoreduction can be achieved
      more often when peritonectomy is included in the surgical treatment of gastric
      cancer with peritoneal dissemination. Phase III data shows prolonged survival
      attributed to complete cytoreduction. Aggressive cytoreduction of peritoneal
      dissemination by peritonectomy can reduce residual tumor burden to
      micrometastases on the peritoneal surface that can be treated by intraoperative
      intraperitoneal chemotherapy and early postoperative intraperitoneal
      chemotherapy. Among all these modalities, surgical cytoreduction is probably the
      most important for survival benefit. If the surgical cytoreduction is visibly
      incomplete, prolonged survival cannot be expected, despite subsequent treatment.
      The surgeon's goal is to reduce the cancer cell burden to a microscopic level.
      Continued refinement of phase II studies is needed for maximal benefit and to
      standardize the technical and chemotherapeutic options of each modality.

PMID- 14567023
TI  - Quantitative prognostic indicators of peritoneal surface malignancy:
      carcinomatosis, sarcomatosis, and peritoneal mesothelioma.
AB  - Quantitative prognostic indicators for carcinomatosis and sarcomatosis are
      essential in the management of peritoneal surface malignancy. This need is
      greatly accentuated as a new comprehensive therapeutic approach emerges. The
      assessment of tumor histopathology, prior surgical score, lesion size, and
      distribution (Gilly classification and peritoneal cancer index) and the
      completeness of cytoreduction scores are the tools that are currently in use.
      Although current assessments have greatly facilitated   clinical research, more
      precise comparisons demand improved quantitation and greater precision.
      Preoperative and intraoperative assessment of peritoneal surface malignancy will
      improve patient selection. Now more than ever, postoperative distribution and
      volume assessments using noninvasive modalities are needed for follow-up.

PMID- 14567024
TI  - The rationale of perioperative intraperitoneal chemotherapy in the treatment of
      peritoneal surface malignancies.
AB  - In summary, the use of perioperative intraperitoneal chemotherapy is a rational
      and scientifically sound treatment option for patients with peritoneal
      carcinomatosis. By delivering chemotherapeutic agents directly into the
      peritoneal cavity in the perioperative period, after cytoreductive procedures
      resulting in minimal residual tumor load, the cytotoxicity, efficacy, and safety
      of these agents can be maximized. The use of this treatment strategy in the
      intraoperative or perioperative period ensures that the efficacy of the
      chemotherapeutic agents is not reduced by limitations of abdominal
      compartmentalization and scarring. Treating patients under hyperthermic
      conditions may confer an additional benefit. Although the use of perioperative
      chemotherapy or hyperthermic intraperitoneal chemotherapy is not yet part of the
      standard of care for the treatment of advanced abdominal malignancies, both basic
      science and clinical investigations have confirmed the validity of these
      regimens. Further clinical studies in a cooperative group setting are necessary
      to prove the efficacy of perioperative intraperitoneal chemotherapy in both the
      treatment and prevention of peritoneal surface malignancy.

PMID- 14567025
TI  - Rationale for hyperthermia with intraoperative intraperitoneal chemotherapy
      agents.
AB  - Hyperthermia is selectively cytotoxic for malignant cells due to inhibition of
      oxidative metabolism causing lower pH in the microenvironment of the malignant
      cells and tumor. The increased acidity increases lysosymal activity and
      subsequent cell death. Hyperthermia alone as a primary treatment modality for
      malignancy has largely been abandoned due to high morbidity and mortality and
      high recurrence rates. Advances in administration and monitoring of hyperthermia,
      especially for regional applications, has allowed for the use of hyperthemia in
      conjunction with other modalities of antineoplastic therapy. Hyperthermia has
      been shown to potentiate chemotherapy and radiation by several different
      mechanisms. HIIC uses the advantages of hyperthermia in conjunction with
      chemotherapy for the management of peritoneal carcinomatosis. Several different
      chemotherapy agents have been shown to have improved therapeutic index and
      efficacy when used with hyperthermia in the management of peritoneal
      carcinomatosis.

PMID- 14567026
TI  - Peritonectomy procedures.
AB  - Treatment of peritoneal surface malignancy requires a combined approach that uses
      peritonectomy procedures and perioperative intraperitoneal chemotherapy. In
      addition, knowledgeable patient selection is mandatory. This article illustrates
      the visceral and parietal peritonectomy procedures that one must use in an
      attempt to resect all visible evidence of disease. Complete cytoreduction is
      essential for treatment of peritoneal surface malignancy to result in long-term
      survival. Several different procedures are required in a single surgical event
      that may require 8-12 hours. Their use depends on the distribution and extent of
      invasion of the malignancy disseminated within the peritoneal space.

PMID- 14567027
TI  - Natural history of peritoneal carcinomatosis from nongynecologic malignancies.
AB  - Both clinical experience and clinical research show that there is a limited
      survival, estimated to be approximately 6 months, in patients with peritoneal
      carcinomatosis from nongynecologic malignancy. Survival is shortest in patients
      with carcinomatosis from pancreas cancer, and is slightly more prolonged with
      colon cancer. The short survival is seen when the diagnosis of carcinomatosis is
      made synchronously with the primary cancer, and also when it is diagnosed in
      follow-up. A large diagnostic shortcoming is the inability to reliably diagnose
      carcinomatosis, either with the primary malignancy or with recurrent cancer. The
      Gilly carcinomatosis staging system has profound prognostic implications in this
      group of patients. The rapid progression of this disease state and the dependence
      of benefit upon complete cytoreduction suggests a need for early interventions in
      selected patients.

PMID- 14567028
TI  - Initiation of a program in peritoneal surface malignancy.
AB  - The initiation of a Program in Peritoneal Malignancy is a long and complex
      process. The novelty, technically demanding nature and steep learning curve that
      characterize this treatment strategy calls for a carefully planned, systematic,
      controlled, and informed introduction is an institution, for which an
      Institutional Review Board approved protocol is suggested. Commitment of a
      surgical team and institution, education of other physician, nurses, and
      ancillary personnel involved in the procedure, safety precaution for patients and
      health care workers, and proper patient selection are important requirements for
      initiating the program. This manuscript provides a guide for implementation of
      this treatment strategy with a minimum of untoward events, reduced apprehension
      of medical and nursing colleagues, and a maximum benefit for patients.

PMID- 14567029
TI  - Pharmacokinetics of heated intraoperative intraperitoneal oxaliplatin after
      complete resection of peritoneal carcinomatosis.
AB  - The results of three prospective clinical trials are reported: the first one was
      aimed at determining the appropriate dose of heated (42 degrees C)
      intraperitoneal oxaliplatin following complete resection of peritoneal
      carcinomatosis by studying its pharmacokinetics. The recommended dosage was set
      at 460 mg/m2 in 2 L/m2 of peritoneal instillation. Using these data another phase
      2 study on 24 patients with colorectal peritoneal carcinomatosis treated with the
      preceding regimen was initiated; the 2-year survival rate was 74% after a minimal
      follow-up of 18 months. A pharmacokinetic study using intraperitoneal oxaliplatin
      at the same dose but in various hypotonic solutions did not show any specific
      pharmacologic advantage and was associated with excessive postoperative bleeding.

PMID- 14567030
TI  - Pharmacokinetics of intraperitoneal mitomycin C.
AB  - The favorable pharmacokinetics of MMC, used during intraperitoneal chemotherapy,
      has been reported in several studies [11-19]. A major safety issue in studies
      using intraperitoneal chemotherapy perfusion is the resulting systemic drug
      exposure. The AUCplasma is determined by the dose, the clearance, and the
      fraction absorbed from the peritoneal cavity. The reported mean plasma peak
      concentrations are about one-third of the systemic exposure following a
      therapeutic dose of MMC given by intravenous administration [30]. The best method
      to quantify the exposure to MMC are the time concentration profiles (AUC).
      Because MMC can still be found in plasma the day after intraperitoneal
      administration, the AUC0-90 is an underestimate of the real AUC; extrapolation to
      infinity gives the most reliable AUCplasma value. In our series the AUCplasma is
      about half the AUCplasma when given a therapeutic dose MMC intravenously [30].
      What is the best dose in intraperitoneal chemotherapy perfusion? The ideal amount
      of MMC should include a high AUCperfusate, a high AUCplasma and an acceptable
      systemic toxicity. In our series grade III/IV leucopenia was observed in 28%
      patients. We find this rather high percentage acceptable as the problem has
      proved to be transient, and we have experienced no toxic deaths in recent years.
      In a phase I study it was estimated that a dose of 25 mg/m2 would result in
      approximately 10% of grade III/IV leucopenia [20]. Our data indicate that dosing
      based on body surface area is rational and reliable. The variation between
      individuals is low. Dosing based on a fixed concentration per liter perfusion
      fluid is probably more liable to have unforeseen variations, given the fact that
      we deal with linear pharmacokinetics of MMC [20]. As represented in Fig. 3, the
      dose of MMC can best be administered in three divided doses, resulting in the
      more equal exposure of peritoneal structures to MMC during the perfusion. It must
      be emphasized that our findings only hold true for the perfusion system as used
      in The Netherlands Cancer Institute. This involves a semi-open abdomen, basic
      perfusate volume of 3 L, perfusion rate of 1 L/min, abdominal temperature of 40
      degrees C, 90 minutes of perfusion, and three drug additions (50% at t = 0, 25%
      at t = 30 and t = 60 minutes). The differences in perfusion techniques make
      comparisons of published pharmacokinetics data difficult. Cautions comparison
      suggest that most groups are dosing far below the maximal tolerated dose. We
      assume that there is a dose-effect relation for MMC. This means that obtaining a
      maximal safe dose is important to get maximal results. It seems that better
      dosing of intraperitoneal MMC can still improve results. The pharmacokinetics of
      intraperitoneal MMC can, however, be influenced by many details. Open or closed
      perfusion for instance may make some essential differences. It is therefore
      important that each treatment group performs its own pharmacokinetics studies on
      intraperitoneal MMC to achieve the optimal dose method for their chemotherapy
      perfusion setting. In conclusion, the major advantage of intraperitoneal
      chemotherapy is the regional dose intensity provided. Following intraperitoneal
      MMC administration, the affected peritoneal surface is exposed to high
      concentrations while the systemic toxicity is limited. Comparative analyses on
      MMC pharmacokinetics are difficult to perform because the diversity of treatment
      techniques. We recommend administration of MMC, divided in three drug additions,
      based on BSA.

PMID- 14567031
TI  - Pharmacokinetics of intraperitoneal cisplatin and doxorubicin.
AB  - Intraperitoneal chemotherapy, mainly when performed during HIIC after
      cytoreductive surgery, is considered potentially curative for the treatment of
      solid tumors with spread to the peritoneal surface. When selecting antiblastic
      agents to be administered intraperitoneally, it is important to bear in mind that
      a low lipophility and a high molecular weight are the ideal drug characteristics.
      Drugs with these features allow a favorable ratio to be achieved between
      peritoneal and plasma concentrations, due to the reduced tendency to diffuse
      through the plasma-peritoneal barrier, even after extensive removal of the
      peritoneum. Moreover, a low rate of diffusion through the tumor capillaries
      implies a low rate of drug clearance, with a higher intratumoral drug
      accumulation. Among the drugs used so far for intraperitoneal chemotherapy, the
      combination of CDDP and DXR appears to be one of the most effective available
      regimens with acceptable local-regional toxicity. CDDP has also been extensively
      employed as a single agent for ovarian and gastrointestinal cancers, under both
      normal and hyperthermic conditions, while intraperitoneally administered DXR
      appears to be of greater potential efficacy when associated with CDDP and
      hyperthermia (41.5 degrees C) following cytoreductive surgery. In our clinical
      experience with this drug combination, DXR showed a much more advantageous
      plasma/peritoneal AUC ratio than CDDP (162 +/- 113 and 20 +/- 6, respectively).
      On the other hand, it has been demonstrated that very high intraperitoneal
      concentrations of CDDP can be achieved without incurring significant systemic
      toxicity by using intravenous injection of sodium thiosulphate during HIIC.
      Penetration of the tumor mass by CDDP is greater than DXR. This phenomenon is
      enhanced by hyperthermia and by hypotonic solutions of sodium chloride used as
      the perfusate. Following experimental and clinical results of TNF alpha-based
      isolated limb perfusion for locally advanced soft tissue sarcoma or melanoma,
      greater efforts are being made to exploit the potential effect of this cytokine
      used in association with hyperthermia and other drugs (i.e., CDDP and DXR)
      suitable for intraperitoneal infusion/perfusion. However, it is not yet clear
      whether the observed effect of TNF alpha on the peritoneal-plasma barrier, which
      seems to favor the passage of both drugs into the systemic circulation, is
      overcome by the positive effect of this agent on drug penetration into tumor.
      Further pharmacologic studies should be undertaken to clarify whether or not
      these interactions will be of benefit to the patient. Likewise, liposomes, which
      in animal models seem to favor tumor uptake of encapsulated DXR, should now be
      tested in the clinical setting.

PMID- 14567032
TI  - Pharmacology of intraperitoneal CPT-11.
AB  - CPT-11 is clearly one of the most important new anticancer drugs developed in the
      last few decades, and CPT-11 combined with 5-fluorouracil (5-FU) and leucovorin
      is considered as reference first-line chemotherapy in the treatment of metastatic
      colorectal cancer. CPT-11 has a complex pharmacologic profile in vivo, and it
      needs caboxylesterase-mediated biotransformation to SN-38 before production of
      its cytotoxic effect. Intraperitoneal administration of CPT-11 has been studied
      recently in murine models and presented some potential advantage over the
      intravenous (i.v.) route. Intraperitoneal administration of CPT-11 may be more
      effective than i.v. administration not only for peritoneal seeding but also for
      liver metastases. Also, these effects may occur with less toxicity by
      intraperitoneal administration. Intraperitoneal chemotherapy containing CPT-11
      might be an essential option for prevention and treatment of cancerous
      dissemination of gastrointestinal malignancy.

PMID- 14567033
TI  - Carrier solutions for intraperitoneal chemotherapy.
AB  - Two pharmacokinetic problems appear to limit the effectiveness of intraperitoneal
      therapy: poor tumor penetration and nonuniform intraperitoneal distribution by
      the drug-containing solution. A better understanding of the pharmacodynamics of
      carrier solutions for intraperitoneal chemotherapy may impact on both these
      problems. Not only is the choice of drug important, but also the matching of the
      chosen drug to an appropriate carrier solution. It would appear that high
      molecular weight solutions offer a number of advantages over low molecular weight
      glucose and saline solutions for chemotherapeutic agents that have a high
      molecular weight with a slow peritoneal clearance. The use of carrier solutions
      of varying tonicity requires further investigation.

PMID- 14567034
TI  - Intraperitoneal taxanes.
AB  - The taxanes appear to be promising agents for intraperitoneal use. Paclitaxel is
      currently undergoing Phase III investigation for the treatment of ovarian cancer.
      Docetaxel requires further Phase II study, but its impressive activity with
      systemic administration may be optimized with intraperitoneal administration for
      the treatment of peritoneal surface malignancy.

PMID- 14567035
TI  - Rationale supporting the use of vasoconstrictors for intraperitoneal chemotherapy
      with platinum derivatives.
AB  - By decreasing drug drainage through the peritoneal and tumoral vascular networks,
      epinephrine increases the penetration of cisplatin and oxaliplatin into the
      metastatic peritoneal tumor nodules. This improved drug penetration increases
      their antitumor efficacy, allowing the cure of millimetric-sized peritoneal tumor
      nodules that could not be obtained with cisplatin or oxaliplatin used alone.
      However, limited drug diffusion into supramillimetric nodules did not result in
      curing advanced peritoneal carcinomatosis, unless complete resection of
      macroscopic localized tumor nodules is performed before intraperitoneal
      chemotherapy. In our opinion, the intraperitoneal epinephrine-cisplatin
      combination should be clinically assessed in completely or almost completely
      surgically resected peritoneal carcinomatosis with the objective of preventing
      recurrent tumors. Due to its reduced toxicity, repeated courses of
      intraperitoneal oxaliplatin associated with epinephrine could be an interesting
      alternative to cisplatin for the unresectable disease.

PMID- 14567036
TI  - Technology of intraperitoneal chemotherapy administration: a survey of techniques
      with a review of morbidity and mortality.
AB  - Peritoneal metastases are a common sequela of gastrointestinal malignancy. The
      treatment of peritoneal metastases through use of aggressive surgical
      cytoreduction including peritonectomy, coupled with IPHC has now been reported in
      several large single institution series. The available literature suggests that
      in experienced hands and with appropriate patient selection, cytoreduction, and
      IPHC can be an effective therapy, particularly when all macroscopic tumor
      deposits are removed. Different techniques involving the administration of
      intraperitoneal chemotherapy have been reported including early postoperative,
      closed intraoperative, the open or coliseum technique, and the open technique
      using a PCE device. All techniques have been associated with low mortality and
      morbidity that is significant, but generally consistent with other major surgical
      procedures. Commonly reported complications of IPHC include prolonged ileus,
      fistula, abscess, and thrombosis. In theory, the coliseum and PCE techniques may
      have less associated morbidity due to improved heat distribution, however, this
      remains to be definitively proven in a controlled clinical trial. Such controlled
      studies are critical to defining the best techniques of IPHC administration and
      the appropriate role for this treatment regimen in patients with peritoneal
      metastases.

PMID- 14567037
TI  - Intraperitoneal chemotherapy with mitoxantrone in malignant ascites.
AB  - A retrospective analysis of intraperitoneal mitoxantrone instillation therapy for
      malignant ascites in advanced breast and gynecologic pelvic cancers was performed
      to confirm the efficacy and safety of this therapy. Several smaller phase II
      trials had suggested good palliative effects. In 143 patients (37 breast cancer
      and 106 gynecologic cancers), 257 instillations were registered. Response in
      breast cancer was induced in 49% and in 63% with gynecologic cancer. Severe or
      life-threatening clinical or laboratory side effects related to intraperitoneal
      mitoxantrone occurred in 2.7% (clinical) or 1.9% (laboratory) of the 257
      instillations. Induction of adverse side effect was dose dependent.
      Intraperitoneal chemotherapy with mitoxantrone for treatment of malignant ascites
      in breast cancer and gynecologic malignancy is effective and well tolerated. For
      this treatment 30 mg mitoxantrone in > or = 1000 mL carrier solution (e.g.,
      saline) is recommended. A minimal concentration of at least 10 micrograms/mL
      should be achieved.

PMID- 14567038
TI  - HIV seroprevalence in emergency department patients: Lagos University Teaching
      Hospital, Lagos, 1999.
AB  - The emergency department patients represent a cross-section of the entire
      population and values of HIV seroprevalence in them have been used to assess the
      general trends of HIV surveillance in other countries. The objectives of this
      study is to determine 1. Whether seroprevalence of HIV antibodies in patients
      attending emergency departments could serve as a marker of prevalence of HIV
      antibody in the general population. 2. The degree of clinical suspicion or
      knowledge of the medical personnel to the status o the HIV seropositive patients
      is also evaluated. A total of 312 emergency department patients of Lagos
      University Teaching Hospital (LUTH) had their blood samples screened for
      antibodies against Human Immunodeficiency Virus (HIV) types I and II by ELISA
      based techniques: Immunocomb II HIV I & II Bispot Kits. Repeatedly reactive
      samples were confirmed by another ELISA based technique using Immunocomb I & II
      Combfirm kits. The attending medical doctor was asked whether there was any
      suspicion or knowledge that the patient being attended to, was HIV seropositive.
      The seroprevalence of HIV antibodies was 5.77% with no significant difference in
      sex incidence. The age groups 20-29 and 30-39 years were most affected. The
      seropositive nature of affected patients was unsuspected by medical personnel in
      55.56% of the HIV antibodies seropositive patients. The Federal Ministry of
      Health in 2000, estimated the National prevalence rate of HIV to have been 5.4%
      in 1998. This figure is comparable to that obtained in this study and revalidates
      the fact that emergency department patients may be used for disease surveillance
      in the population. The seropositive status of majority of the HIV positive
      patients was unsuspected by the attending medical personnel. Thus, strict
      adherence to universal safety precautions is essential for all medical personnel.
      Post exposure prophylaxis should be made readily accessible to all medical
      personnel.

PMID- 14567039
TI  - Ventricular arrhythmias: Q-T prolongation and left ventricular hypertrophy in
      adult Nigerians with hypertensive heart disease.
AB  - Seventy adult Nigerians with hypertensive heart disease (HHD) and 68 healthy
      controls were studied for ventricular arrhythmias (VA). The roles of QT
      prolongation and left ventricular hypertrophy in these arrhythmias were received.
      The mean age of the study population was 49.9 +/- 6.0 years. 14 (20.0%) patients
      had cardiac arrhythmias with 3 patients having premature ventricular contractions
      (PVC). Ten (14.3%) cases had QTc prolongation out of which 1 patient had PVC.
      Some factors that were found to be associated with QT prolongation in HHD
      include: left ventricular hypertrophy, persistently elevated systolic blood
      pressure and female gender. There was a positive correlation between left
      ventricular hypertrophy and QTc prolongation and also between QTc prolongation
      and frequency of ventricular arrhythmias.

PMID- 14567040
TI  - Hepatitis C virus infection in patients with sickle cell anaemia at the Lagos
      University Hospital.
AB  - The objective of this studies is to determine the frequency of antibodies to
      Hepatitis C virus (anti-HCV), (2) assess the role of blood transfusion in
      transmission of infection, and (3) evaluate the clinical implication of anti-HCV
      sero-positivity in patients with Sickle cell anaemia (SCA). Two hundred and
      seventy-eight (278) patients with SCA were evaluated by questionnaire interviews
      for risk factors, clinical examination and serum testing for anti-HCV using a
      third generation ELISA kit. The overall anti-HCV prevalence was 5.0% (14/278).
      Anti-HCV was positive in 7% (5/76) of never transfused compared with 5% (9/202)
      of previously transfused sicklers. (p = 0.5). Clinically, splenomegaly alone or
      in combination with hepatomegaly was associated with a positive anti-HCV (p =
      0.04 and 0.01 respectively). Anti-HCV was detected in 5% of adult patients with
      Sickle cell anaemia, especially in patients with persistent splenomegaly alone or
      in combination with hepatomegaly. Blood transfusion did not appear to be the
      major route of HCV transmission.

PMID- 14567041
TI  - Prevalence of cryptosporidium infection among undernourished children in Jos,
      Central Nigeria.
AB  - This prospective study aimed at determining the prevalence data of
      Cryptosporidium infection in undernourished children, its seasonality and its
      relative frequency in diarrhoeic stool in Jos, Central Nigeria. One hundred and
      seventy each of undernourished and well nourished children aged 0-5 years were
      recruited into the study. Stool samples and clinical data were obtained using
      questionnaires. Results were analysed using Chi-square test. The prevalence of
      the infection was found to be 4.8% and all infections occurred in diarrhoeic
      stool. No infection with this pathogen was recorded in the well-nourished group.
      There was a defined seasonality of the infection. The high prevalence suggests
      the importance of introducing routine screening of this group of patients for
      cryptosporidium infection to facilitate their management.

PMID- 14567042
TI  - Prosthetic parameters among dental patients in Ile-Ife, Nigeria.
AB  - The purpose of this study was to determine the Rest Vertical Dimension (RVD),
      Occlusal Vertical Dimension (OVD), Freeway Space (FWS) and their importance in
      the fabrication of dental prostheses. These prosthetic parameters were determined
      in 310 dentate patients attending the Dental Hospital of the Obafemi Awolowo
      University Teaching Hospitals' Complex Ile-Ife. The MMO was obtained by measuring
      inter-incisal distance. RVD and OVD were derived using Willis gauge. The FWS was
      taken as 'RVD minus OVD'. Of the 310 attendees, twenty-seven (8.7%) were denture
      wearers. There was no statistically significant difference between the genders
      with regards to the use of dentures (P = 0.17). The mean values (+/- standard
      deviation) for MMO was found to be 50.5 +/- 7.9 mm (range 18.0 to 70.0 mm). The
      RVD was 73.0 +/- 8.4 mm (range 50.0 to 94.0 mm) and OVD was 69.8 +/- 8.2 mm
      (range 47.0 t 92.0 mm). The mean FWS was 3.3 +/- 1.4 mm (range 1 to 9 mm).
      Following the loss of most of the posterior teeth or in a state of complete
      edentulism, the face profile appears squashed and the vertical dimensions are
      altered. To provide an efficient and functional prosthesis, the facial dimensions
      have to be restored to or near pre-edentulous state. The establishment of values
      for these facial dimensions in given population will assist in the provision of
      satisfactory prosthesis.

PMID- 14567043
TI  - Clinical and management factors related to outcome in neonatal tetanus.
AB  - Although tetanus is a well-recognised, well-described, preventable and eradicable
      infection, it continues to ravage the lives of children in developing countries,
      especially among neonates. A cross-sectional review of cases of neonatal tetanus
      seen in LUTH was carried out retrospectively. Thirty-nine (39) cases were
      studied, comprising 26 (63.4%) males and 15 (36.6%) females, giving a male:
      female ratio of 1.6:1. Case fatality rate was 10.3%, thirty-five (89.7%) cases
      survived, of which nine (23.8%) survived with complications. Clinical factors
      that influence outcome were: a short interval between onset and presentation (p =
      0.03), low tetanus score below 6.0 (p = 0.002), hyperpyrexia (p = 0.0001), heart
      failure (p = 0.035), cyanosis (p = 0.008) and crepitations (p = 0.003). Although
      several management factors were associated with mortality, these failed to meet
      statistical significance (p > 0.05). In this study, clinical factors, including
      presentation interval, were the principal determinants of outcome. The need for
      intensification and sustenance of preventive measures, early recognition and
      presentation, prompt treatment as well as improved care are emphasised. We
      recommend periodic audit of patient clinical data towards improving quality of
      care.

PMID- 14567044
TI  - Comparative study of salt taste threshold of hypertensives, their normotensive
      relatives and non-relatives.
AB  - The role of salt in the genesis of hypertension has been well documented. Earlier
      studies have demonstrated higher salt taste threshold among hypertensives
      compared to normotensives. The aim of this study is to compare the salt taste
      thresholds of normotensive relatives of hypertensive patients with those of
      normotensives without family history of hypertension. Twenty-one hypertensives,
      52 first degree relatives of these hypertensives and 99 normotensives without
      family history of hypertension were studied. They were made to taste different
      concentrations of solution from distilled water to 280 mmol of saline. The
      results showed that hypertensives had higher salt taste thresholds--detection (p
      < 0.0001), recognition (p < 0.0001) and maximum tolerable threshold (p < 0.05)-
      compared with normotensive relatives. The normotensive relatives of hypertensive
      patients in turn had higher salt taste thresholds--detection (p < 0.01),
      recognition (p < 0.0001) and maximum tolerable threshold (p < 0.001)--compared
      with normotensive controls; they also had significantly higher mean arterial
      pressure (p < 0.001). Health education with intervention directed at the
      hypertensives and their first degree normotensive relatives to willfully modify
      their desire and appetite for salt is of paramount importance.

PMID- 14567045
TI  - Malignant tumours of the nasopharynx at Jos University Teaching Hospital,
      Nigeria.
AB  - A retrospective epidemiological study of 55 patients who had been histologically
      diagnosed as having nasopharyngeal malignancy was undertaken at the Jos
      University Teaching Hospital in the period from December 1988 to November 1998.
      Jos is at the heart of the middle belt of Nigeria and is made up of peoples of
      various tribes and religions. The aim of this study was to evaluate the
      epidemiological factors, clinical presentation, histological pattern and
      treatment outcome in the patients during the study period. Fewer females were
      affected than males with a ratio of 1:1.6. Age range was 35-82 years with an
      average age of 42.19 years. Most of the well documented predisposing factors were
      absent in this series and the role of smoking and alcohol is unclear. Squamous
      cell carcinoma (72.7%) was the commonest epithelial malignancy with the incidence
      of the well differentiated type (WHO type 1) being as high as 34.5%.
      Rhabdomyosarcoma (14.8%) was the commonest sarcoma. Neck swelling 70.9%, Nasal
      stuffiness 41.8%, epistaxis 34.5% and pharyngeal mass 25.5% were the commonest
      symptoms. Treatment and follow-up were unsatisfactory as patients could not
      afford the cost of radiotherapy and anti-cancer drugs.

PMID- 14567046
TI  - Prognostic factors in the management outcome of carcinoma of the larynx in Lagos.
AB  - This is a retrospective analysis on the prognostic factors in the management
      outcome of clinically and histologically diagnosed carcinoma of larynx seen in
      Lagos University Teaching Hospital between 1996-1999. Various prognostic factors
      have been documented as determinants on the probable outcome of carcinoma of the
      larynx, such as duration of symptoms, smoking, medical status of the patient,
      degree of differentiation, size and site of tumour and presence of cervical lymph
      node. Thirty-six patients between 1996-1999 were reviewed, with a male to female
      ratio of 11:1, and peak age group of occurrence in 50-59 years, majority (86.12%)
      of which were non-smokers who presented in varied degrees of airway obstruction
      necessitating pre-treatment tracheostomy in 70% of the patients with more than
      50% presenting within 3-6 months of onset of initial symptom. The tumours were
      staged clinically and histology revealed well differentiated T3 glottic tumour
      without any clinically palpable neck node in more than 50% of the patients which
      should predict a better outcome. But the interplay of many prognostic variables
      like pre-treatment tracheostomy and its attendant complications, supposed
      biological aggressive tumour in a non-smoker, coupled with treatment biased by
      patients, high costs of treatment, logistics and poor follow up compliance,
      resulted in poor outcome of our management.

PMID- 14567047
TI  - Perianal abscess and fistula in children in Zaria.
AB  - Perianal abscess (PAA) and fistula-in-ano (FIA) are not uncommon in children, but
      reports from tropical Africa are uncommon. In a period of 17 years, 17 children
      aged 12 years and below were treated for these conditions in Zaria, Nigeria.
      There were 14 boys and 3 girls, aged 4 months-12 years (median 3 years), Eight
      had PAA (median age 3 years), 5 ischiorectal abscess (median age 5 years) and 4
      FIA (median age 10 months). FIA followed pull through for anorectal malformation
      in 2 patients and in one it was preceded by PAA. PAA was associated with chronic
      fissure-in-ano in one patient and uncontrolled diabetes mellitus in one. One 16
      month girl with an ischiorectal abscess developed severe perineal necrotising
      fascitis and separation and retraction of the anorectum. Escherichia coli was
      cultured in 2 patients with abscesses and staphylococcus aureus in another 2.
      Culture was sterile in 7 patients with abscesses. Treatment was by adequate
      incision and drainage for abscesses. Fistulectomy was the treatment for FIA, but
      in one patient a diversion colostomy was performed in addition as the fistula was
      a high one. The child who developed necrotising fascitis had debridement and
      diversion colostomy. FIA recurred in one patient necessitating repeat
      fistulectomy. Although the number of patients is small, perianal sepsis appears
      to be less common in our environment compared to developed countries. Some
      differences are highlighted.

PMID- 14567048
TI  - Two vaginal deliveries after a classical caesarean section--case reports.
AB  - It is standard practice to offer a parturient who has had a classical Caesarean
      section an elective repeat Caesarean section due to the fear of uterine rupture.
      The strong aversion of our women to operative delivery does not allow an
      appreciable number to avail themselves of hospital delivery even after Caesarean
      section. We report the case of a booked patient who had a classical Caesarean
      section but defaulted in two subsequent pregnancies to have vaginal deliveries in
      a private hospital. We therefore suggest a more liberal attitude to allowing
      attempt at vaginal delivery as an informed decision in well-equipped facilities
      capable of easy and prompt resort to appropriate intervention.

PMID- 14567049
TI  - Abruptio placenta following sexual intercourse: case report.
AB  - This is a case of Abruptio Placenta resulting from sexual intercourse. Pelvic
      Examination revealed active bleeding per vaginam. The pregnancy resulted into
      intra-uterine foetus death. The foetus membranes were ruptured and labour
      progressed. A still born male baby was delivered.

PMID- 14567050
TI  - Diabetic retinopathy: management update.
AB  - The objective of the study is to review the current knowledge and management of
      diabetic retinopathy. Current information from multi-centre controlled clinical
      trials and epidemiological studies in different parts of the world were used to
      review the epidemiology, pathophysiology, classification, clinical features and
      management of diabetic retinopathy. Diabetes mellitus affects all ocular tissues.
      Retinopathy, its most devastating ocular complication, presents with similar
      clinical picture in both types 1 and 2 diabetes. In Nigeria, diabetic retinopathy
      has an incidence of 33%; accounts for 16.7% of retinal diseases and leads to
      bilateral blindness in 22.2% of diabetics. Its incidence depends on both the
      duration of diabetes and the level of glycaemic control. Hypertension,
      dyslipaemia, hyperglycaemia and cigarette smoking aggravate retinopathy and
      adversely affect its response to treatment. Strict blood sugar control delays the
      onset of retinopathy and retards the progression of established disease. Timely
      laser and vitrectomy surgeries obviate severe visual loss in diabetic
      retinopathy. The role of medical therapy for diabetic retinopathy is still
      experimental. Diabetes occurs worldwide; diabetic retinopathy is increasing in
      incidence. Developed countries have clear guidelines on the care of diabetes and
      its complications. The need for similar guidelines in Nigeria is urgent.

PMID- 14567051
TI  - Helicobacter pylori: pathogen and symbiont.
AB  - There are puzzles in defining the exact role of Helicobacter pylori infection in
      humans. The bacterium, which is associated with human disease of the upper
      gastrointestinal tract, may otherwise exist as a commensal with probable
      symbiotic association in some human hosts. Although virulence associated genes
      have been detected in some strains which explain their pathogenicity, their
      pathogenic effect and subsequent clinical manifestations seem to vary in
      different human populations or geographical locations. Some human hosts remain
      predominantly asymptomatic in spite of the "virulent" H. pylori strain(s) they
      harbour. There are probable benefits of H. pylori colonisation of the human
      gastric mucosa. Thus the recommendation of eradication therapy in patients with
      known peptic ulcer disease may be more advantageous than the "test and treat
      policy", which suggests treatment of uninvestigated dyspeptic patients, who may
      not have any lesions.

PMID- 14567052
TI  - Autogenous arteriovenous fistulas for haemodialysis: a review.
AB  - The last 40 years has witnessed revolutionary changes in vascular access
      provision for haemodialysis. Autogenous arteriovenous (AV) fistula is the best
      access modality and should be considered first when planning vascular access.
      Education is required to ensure preservation of the cephalic veins in patients at
      potential risk for the development of end stage renal disease (ESRD). The best
      access procedure should be performed first and the AV fistula allowed to mature
      before use. Autogenous AV fistula have a cumulative patency of 85-90% and 60-85%
      at 1 and 3 years respectively. Increased use of preoperative imaging and the use
      of autogenous vein are essential to improved long-term results.

PMID- 14567053
TI  - Mycobacterial infections of the head and neck.
AB  - Mycobacterial infections are grouped into infections caused by M. tuberculosis
      and those caused by the atypical mycobacterial organisms. Tuberculosis is a
      systemic disease, with cervical lymphadenitis of the head and neck being the most
      common extrapulmonary manifestation of the disease. It is important to use
      imaging, histopathologic examination, and culture to differentiate tuberculosis
      from atypical mycobacterial infections, because treatments differ. Tuberculosis
      is best treated as a systemic disease, with anti-tuberculosis medication. The
      atypical infections can be addressed as local infections and are amendable to
      surgical therapy.

PMID- 14567054
TI  - Fungal infections of the head and neck: an update.
AB  - Despite the vast literature regarding fungal infections of the head and neck,
      little has changed in diagnosis or management of these infections except in the
      nose and sinuses. Three main points regarding fungal involvement in the paranasal
      sinuses are evident now. First, fungi may be important in a significant
      percentage of patients with chronic rhinosinusitis. Second, the pathophysiologic
      mechanism responsible for fungal rhinosinusitis remains unclear. It may represent
      an allergic IgE response, a cell-mediated reaction, or a combination of the two.
      Finally, there is certainly a spectrum of disease thus far defined: allergic
      fungal sinusitis as defined by Bent and Kuhn [35], eosinophilic mucin
      rhinosinusitis defined by Ferguson [50], and eosinophilic fungal rhinosinusitis
      as proposed by Ponikau [45]. Fungal infections of the head and neck are panoramic
      in distribution and pathophysiology. They represent a broad range of disease of
      which medical science has only recently begun to uncover the surface. As research
      begins to unravel the complex host defense mechanisms against these pathogens
      from a cellular and even genetic level, the body of knowledge will continue to
      increase exponentially and the ability to treat patients suffering from fungal
      infections will improve.

PMID- 14567055
TI  - Syphilis and otolaryngology.
AB  - Syphilis is the oldest known sexually transmitted disease. Because of its
      multiple clinical manifestations it is known as "the great imitator." Although
      the antibiotic era has greatly diminished the prevalence of syphilis, sporadic
      outbreaks continue to occur. Because of its multiple head and neck
      manifestations, the otolaryngologist should be familiar with the basic
      pathogenesis and clinical presentations of this disease.

PMID- 14567056
TI  - Otolaryngologic manifestations of human immunodeficiency virus infection.
AB  - The otolaryngologist is uniquely positioned to detect and pursue manifestations
      of HIV in the head and neck. The presentation of problems subsequent to HIV
      infection is quite varied, but close investigation will often reveal treatable
      problems.

PMID- 14567057
TI  - Lymphomas.
AB  - Hodgkin's and non-Hodgkin's lymphomas are an important part of the differential
      diagnosis of head and neck tumors. Their diagnosis begins with a complete history
      and physical examination and is confirmed with an appropriately obtained and
      prepared pathologic specimen. Prognosis and therapy of the lymphomas vary
      depending on stage and the characteristics of each particular subtype of
      lymphoma. Low-grade lymphomas and chronic lymphocytic leukemia are characterized
      by long survival times and are most often treated with palliative intent. More
      aggressive high-grade lymphomas are treated for cure. Although chemotherapy and
      radiotherapy remain the mainstays of treatment, immunotherapy demonstrates
      increasing promise.

PMID- 14567058
TI  - Otolaryngologic manifestations of immunodeficiency.
AB  - Otolaryngologists are frequently consulted to manage infectious and noninfectious
      complications of immune deficiency. Although defects of host defense and
      recurrent or severe infections are the most obvious manifestations of immune
      deficiency, patients are often at increased risk for autoimmune and malignant
      disease as well. Knowledge of primary and acquired immune deficiencies will
      facilitate appropriate identification, treatment, and referral of patients with
      these defects. When immunodeficiency is known or suspected, it is particularly
      important to have a high index of suspicion for unusual or severe manifestations
      of infection, to have a low threshold for obtaining imaging to aid in diagnosis,
      and to treat infections for longer periods of time with higher doses of
      antibiotic. Surgery may be required for definitive treatment of infections that
      do not respond to medical therapy and for management of complications of
      infectious disease

PMID- 14567059
TI  - Ear, nose, and throat manifestations of sarcoidosis.
AB  - Sarcoidosis rarely affects the head and neck and represents a diagnostic
      challenge to the otolaryngologist. The signs and symptoms of sarcoidosis in this
      area are not specific and can mimic much more common disorders. Biopsy is usually
      necessary to make the diagnosis. Appropriate evaluations and referrals should be
      made once there is suspicion of sarcoidosis. Steroids remain the mainstay of the
      therapeutic options; however, newer agents are being used more frequently. Long
      term treatment and follow-up are necessary, because the disease tends to progress
      and to respond unpredictably to treatment.

PMID- 14567060
TI  - Head and neck manifestations of Wegener's granulomatosis.
AB  - Wegener's granulomatosis is an idiopathic, granulomatous disease with the
      potential for multiple head and neck manifestations. The otolarygologist is an
      essential part of the multidisciplinary team involved in establishing the
      diagnosis and providing ongoing care for patients with Wegener's granulomatosis.
      Diagnostic difficulties abound in Wegener's granulomatosis, making repeat
      biopsies and the use of ANCA imperative. Medical therapy consisting of
      corticosteroids and immunosuppressive agents is the mainstay of treatment in
      Wegener's granulomatosis, whereas surgery is reserved for selected head and neck
      manifestations. With appropriate medical and surgical treatment, many patients
      living with Wegener's granulomatosis can enjoy a good quality of life.

PMID- 14567061
TI  - Paget's disease and fibrous dysplasia.
AB  - Paget's disease and fibrous dysplasia are benign disorders that can involve the
      temporal bone and skull base. They commonly lead to otolaryngologic symptoms such
      as impingement of cranial nerves or the orbit or blockage of the external
      auditory canal or paranasal sinuses, although they can often be a challenge to
      diagnose because of their insidious presentation. Their benign nature and common
      presentation within the difficult-to-access confines of the skull base should
      lead the clinician to exercise caution in their treatment, reserving surgical
      intervention for either diagnosis or the relief of symptoms. As a better
      understanding of the etiology of these conditions develops and new
      pharmacotherapeutic agents are tested, it is likely that physicians will be able
      to turn to medical rather than surgical techniques to treat these disorders.

PMID- 14567062
TI  - Sjogren's disease.
AB  - In summary, Sjogren's syndrome is a chronic autoimmune disorder characterized by
      lymphocytic infiltration of the exocrine glands, particularly the salivary and
      lacrimal glands. The sicca complex of xerophthalmia and xerostomia are the
      hallmark features of Sjogren's symptomatology. In addition to these hallmark
      symptoms of oral and ocular dryness, one third of patients with Sjogren's
      syndrome present with extraglandular manifestations. Many osf these
      extraglandular manifestations, as well as the sicca symptoms, have
      otolaryngologic relevance. Because patients with Sjogren's syndrome may present
      with vague or nonspecific head and neck complaints, ranging from oral dryness to
      hoarseness to hearing loss, an otolaryngologist's high index of suspicion for
      this disorder may prevent delay in diagnosis, allow appropriate diagnostic
      evaluation, and optimize therapeutic intervention.

PMID- 14567063
TI  - Plasma cell dyscrasias and amyloidosis.
AB  - The plasma cell dyscrasias and amyloidosis are distinct clinical entities that
      may co-exist. Both disease processes may present with manifestations in the head
      and neck, making familiarity with these conditions by otolaryngologists
      essential. Prompt diagnosis and evaluation for systemic disease are crucial in
      proper treatment planning.

PMID- 14567064
TI  - Aqueous extract of Ocimum canum decreases levels of fasting blood glucose and
      free radicals and increases antiatherogenic lipid levels in mice.
AB  - The basis for managing diabetes mellitus with aqueous extract of Ocimum canum Sim
      (Lamiaceae), in Ghana was investigated in diabetic and normoglycemic mice. In the
      diabetic mice, fasting blood glucose decreased by 60% compared to 10% in control
      mice after 13 weeks of extract administration. Body weight, serum total
      cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) decreased while
      serum high-density lipoprotein cholesterol (HDL-C) increased in the extract
      treated group. In vitro hydroxyl (OH) and superoxide (O2) radical formation, and
      lipid peroxidation of isolated human LDL and mouse liver homogenates decreased in
      extract-treated experimental systems. These findings justify the use of O. canum
      extract as an antidiabetic folk medicine.

PMID- 14567065
TI  - Effects of berberine on angiotensin-converting enzyme and NO/cGMP system in
      vessels.
AB  - The present study was designed to examine the relaxant and anticonstrictive
      effects of berberine in the isolated thoracic aorta in rats. Intravenous
      injection of berberine lowered the mean arterial pressure (MAP) of anesthesized
      rats in a dose-dependent manner. The angiotensin-converting enzyme (ACE)
      activities were inhibited significantly by the addition of berberine in a dose
      dependent manner of which the IC50 value of berberine for ACE was 42
      micrograms/ml (125 microM). In the endothelium-intact rings, angiotensin I
      induced contraction was markedly attenuated by prior exposure of aortic rings to
      berberine. Treatment of the intact aortic rings with berberine (10 micrograms/ml)
      increased the NOx and cGMP productions relative to the vehicle-treated group.
      Berberine induced a dose-dependent relaxation in phenylephrine-precontracted
      aortic rings, but NG-nitro-L-arginine methyl ester (L-NAME)-pretreated intact
      aortic rings or functional removal of the endothelium attenuated the berberine
      induced relaxation without an effect on maximum response. These results suggest
      that berberine has a hypotensive effect, at least in part, via the inhibition of
      ACE and direct release of NO/cGMP in the vascular tissues.

PMID- 14567066
TI  - Histamine-induced vasodilatation in the perfused mesenteric arterial bed of
      diabetic rats.
AB  - In this study, we have examined the contribution of endothelium-derived nitric
      oxide (EDNO) and endothelium-derived hyperpolarizing factor (EDHF) to histamine
      induced endothelium-dependent relaxation in the perfused mesenteric arterial bed
      of rats treated with streptozotocin (STZ) to induce diabetes. Histamine (10(-10)
      to 5 x 10(-6) mol) produced dose-dependent vasodilator response in the perfused
      mesenteric arterial bed of both control and diabetic animals. In order to isolate
      the EDHF component of histamine-induced vasodilator response, NG-nitro-L-arginine
      methyl ester hydrochloride (L-NAME) (10(-4) M) and indomethacin (10(-6) M) were
      added to the Krebs solution throughout the experiment. Histamine induced
      vasodilatation in the perfused mesenteric bed in preparations from both control
      and diabetic rats. The vasodilator response to histamine was slightly potentiated
      in the diabetic rat preparations. Sodium nitroprusside (SNP)-induced relaxation
      was similar in diabetic and control rats. The role of EDNO in histamine-induced
      vasodilatation was also examined. Vascular preparations were perfused with 20 mM
      K(+)-Krebs solution to inhibit the EDHF contribution to histamine-induced
      vasodilatation. Under this condition, histamine induced a vasodilator response in
      preparations from both control and diabetic rats. However, relative to
      nondiabetic control animals, histamine-induced maximal response was significantly
      reduced in preparations from diabetic animals. Pretreatment with L-NAME (10(-4)
      M) attenuated histamine-induced vasodilatation in both preparations, indicating
      an NO-mediated vasodilator response. There was a significant attenuation in
      histamine-induced vasodilatation in the vascular preparations from diabetic rats.
      The vasodilator effect of calcium ionophore A23187 was investigated in
      preparations from control and diabetic rats to investigate receptor dysfunction
      associated with diabetes. A23187 (10(-11) to 10(-7) mol)-induced vasodilator
      response was not significantly different in the preparations from control and
      diabetic animals. In conclusion, our results indicated that histamine-induced
      vasodilation in the perfused mesenteric arterial bed of the STZ-induced diabetic
      rats is mediated by two vasodilator components, namely EDHF and EDNO. Under
      diabetic conditions, the EDHF component was potentiated, while histamine-induced
      vasodilation mediated by the EDNO component was attenuated.

PMID- 14567067
TI  - Adenoviral delivery of a constitutively active retinoblastoma mutant inhibits
      neointima formation in a human explant model for vein graft disease.
AB  - Intimal hyperplasia resulting from vascular injury remains a major obstacle in
      the long-term success of coronary artery bypass grafts. Inhibition of smooth
      muscle cell (SMC) proliferation using adenoviral gene transfer of cell cycle
      inhibitors resulted in reduced neointima formation in various animal models.
      However, little is known about the effect on human SMCs and neointima formation.
      Here we report the effects of infection with an adenoviral vector encoding a
      constitutively active form of the retinoblastoma gene (Ad. delta Rb) on
      proliferation of human saphenous vein SMCs (HSVSMCs) and neointima formation in
      organ cultures of human saphenous vein. Proliferation of SMCs was inhibited dose
      dependently after infection with Ad. delta Rb. A near-total inhibition was found
      at an Ad. delta Rb concentration of 10(8) pfu/ml. Organ cultures of human
      saphenous vein segments were used to evaluate the effect of Ad. delta Rb
      infection on neointima formation and vein graft disease. Segments cultured for 4
      weeks develop a neointima that is morphologically highly similar to early
      initimal lesions found in pathological vein grafts in vivo. Infection of
      saphenous vein segments with 2 x 10(9) pfu/ml Ad. delta Rb resulted in a 59%
      reduction of neointimal area when compared to uninfected counterparts, whereas
      infection with control adenovirus, Ad.LacZ, had no significant effect. The
      results of this study show that Ad. delta Rb gene transfer might be an efficient
      approach to prevent neointima formation in human saphenous vein grafts.

PMID- 14567068
TI  - Anti-inflammatory effect of kaurenoic acid, a diterpene from Copaifera
      langsdorffi on acetic acid-induced colitis in rats.
AB  - Kaurenoic acid, a diterpene from Copaifera langsdorffii (Leguminaceae), was
      evaluated on rat colitis induced by acetic acid. Rats were pretreated orally (15
      and 2 h before) or rectally 2 h before induction of colitis with kaurenoic acid
      (50 and 100 mg/kg) or vehicle (1 ml, 3% DMSO). Colitis was induced by
      intracolonic instillation of a 2 ml of 4% (v/v) acetic acid solution and, 24 h
      later, the colonic mucosal damage was analysed macroscopically for the severity
      of mucosal damage, the myeloperoxidase (MPO) activity and the malondialdehyde
      (MDA) levels in the colon segments. A marked reduction in gross damage score (52%
      and 42%) and wet weight of damaged colon tissue (39% and 32%) were observed in
      rats that received 100 mg/kg kaurenoic acid, respectively, by rectal and oral
      routes. This effect was confirmed biochemically by a two- to three-fold reduction
      of colitis associated increase in MPO activity, the marker of neutrophilic
      infiltration and by a marked decrease in MDA level, an indicator of
      lipoperoxidation in colon tissue. Furthermore, light microscopy revealed the
      marked diminution of inflammatory cell infiltration and submucosal edema
      formation in the colon segments of rats treated with the test compound. These
      findings indicate the anti-inflammatory potential of kaurenoic acid in acetic
      acid-induced colitis.

PMID- 14567069
TI  - Evaluation of reactive blue 2 derivatives as selective antagonists for P2Y
      receptors.
AB  - P2Y receptor pharmacology is hampered by a lack of subtype selective antagonists.
      However, a recent study evaluated series of compounds, structurally related to
      the dye reactive blue 2, for their antagonist selectivity at P2X vs. P2Y
      receptors. Acid blue 129, acid blue 80, acid blue 25 and acid violet 34 were
      found to be the most potent of the antagonists studied, at P2Y receptors [Naunyn
      Schmiedeberg's Arch. Pharmacol. 357 (1998) 111]. In this study, we have
      determined the ability of these four agents to selectively antagonize inositol
      phosphate turnover mediated by P2Y1 and P2Y2 receptors that are natively
      expressed in bovine aortic endothelial (BAE) cells. Acid blue 129, acid blue 80,
      and acid violet 34 shifted the dose-response curve of the P2Y1 agonist 2
      methylthio adenosine trisphosphate (2MeSATP) to the right. Acid blue 129 and acid
      blue 80 were also very weak antagonists of the P2Y2 agonist uridine 5'
      triphosphate (UTP). At 30 and 100 microM, acid violet 34 failed to have any
      significant effect on the dose-response to UTP. However, at 10 microM, acid
      violet 34 enhanced the UTP responses. Acid blue 80, acid blue 129 and acid violet
      34 are P2Y vs. P2X selective, but show poor selectivity between P2Y1 and P2Y2
      receptors and are therefore of limited use in the field of P2Y receptor
      pharmacology. Furthermore, contrary to previous reports, acid blue 25 is not a
      P2Y-selective antagonist.

PMID- 14567070
TI  - The influence of Sacoglottis gabonensis stem bark extract and its isolate
      bergenin, Nigerian alcoholic beverage additives, on the metabolic and
      haematological side effects of 2,4-dinitrophenyl hydrazine-induced tissue damage.
AB  - This study was designed to study the influence of Sacoglottis gabonensis stem
      bark extract on the metabolic and cytotoxic side effects of 2,4-dinitrophenyl
      hydrazine (2,4-DNPH) on the brain and blood using male weaving rats as the
      experimental model. This was after the effect of the bark extract and bergenin,
      its isolate, on membrane lipid peroxidation and tissue natural antioxidant
      defences was reported. Lipid peroxidation was induced experimentally with a
      single intraperitoneal phenylhydrazine (2,4-DNPH) administration at the end of 3
      days exposure to the bark extract or bergenin in drinking water. Three hours
      later, the brain, liver and red blood cells of the experimental animals were
      analysed for glucose level and the blood was analysed for selected key indices of
      oxidative stress: red blood cell (RBC) count haemoglobin (Hb), packed cell volume
      (PCV) and white blood cell (WBC) count (total and differential). The bark extract
      exhibited a protective action on brain glucose, significantly inhibiting the
      glucose-depleting action of both 2,4-DNPH and ethanol. It also inhibited the
      lowering action of DNPH and ethanol on PCV, RBC and Hb concentration of rat
      blood, but inhibited proliferation of white blood cells (total and differential).
      The data on the effect of bergenin, on the side effects of 2,4-DNPH experimental
      lipid peroxidation and on ethanol followed an essentially similar trend to those
      of the bark extract on brain glucose. Bergenin, similar to the bark extract,
      exerted a protective action on the brain tissue, though to a lesser extent,
      against the oxidants, 2,4-DNPH and ethanol. It is evident that aqueous ethanol
      extract of S. gabonensis stem bark has biological antioxidant properties against
      2,4-DNPH and ethanol-induced tissue damage exerting its action on the
      haematological and metabolic side effects of the oxidants. By virtue of its
      essentially similar activity under the same conditions, bergenin appears to be
      the phytochemical constituent that is largely responsible for the observed action
      of the bark extract.

PMID- 14567071
TI  - Marked neuropeptide Y-induced contractions via NPY-Y1 receptor and its
      desensitization in rat veins.
AB  - The aim of this study was to investigate neuropeptide Y (NPY)-induced
      vasoconstrictions in rat blood vessels and which NPY receptor subtype is involved
      in vasoconstrictions. NPY produced marked contractions in rat common jugular,
      brachial, portal, femoral and tail veins, and vena cava inferior, whereas it
      produced little or no contractions in rat common carotid, brachial, femoral and
      tail arteries, and thoracic and abdominal aortae. The maximal NPY-induced
      contractions were larger than maximal phenylephrine (PE)-induced contractions in
      the veins. These NPY-induced contractions were blocked by the Y1 antagonists, SRL
      21, and BIBP3226 but not by the Y5 antagonist, L-152804. A Y2 agonist, NPY (13
      36), did not produce contractions. RT-PCR showed that NPY-Y1 was the only
      receptor subtype in the veins indicating that NPY-induced contractions are
      mediated through the Y1 receptor. Pretreatment with NPY showed a rapid and long
      lasting desensitization of these contractions. The marked NPY-induced
      contractions and its desensitization in the veins suggest the physiological
      relevance of NPY in the venous circulation.

PMID- 14567072
TI  - Effects of castration on alpha 1-adrenoceptor subtypes in the rat aorta.
AB  - The expression of alpha 1-adrenoceptor subtypes in several tissues is regulated
      by gonadal hormones. In this study, we investigated whether castration regulates
      the alpha 1-adrenoceptor subtypes mediating the contractions of the aorta from
      male rats to noradrenaline. Noradrenaline induced similar concentration-dependent
      contractions in the aorta from control and castrated rats. Treatment of the aorta
      from both control and castrated rats with the alpha 1B/alpha 1D-adrenoceptor
      alkylating agent chloroethylclonidine resulted in approximately 1600-fold
      rightward shift in the concentration-response curves to noradrenaline. The pA2
      values found for WB 4101, benoxathian (alpha 1A-selective) and BMY 7378 (alpha 1D
      selective) indicate that alpha 1D-adrenoceptors are involved in the contractions
      of the aorta from control and castrated rats to noradrenaline. However, there was
      a 15-fold difference between the pKB estimated through the lowest effective
      concentrations of the alpha 1A-adrenoceptor selective antagonist 5-methyl
      urapidil in the aorta from control and castrated rats. The pKB estimated in aorta
      from control rats is consistent with the interaction with alpha 1D-adrenoceptors
      (7.58 +/- 0.06), while that calculated in organs from control rats is consistent
      with alpha 1A-adrenoceptors (8.76 +/- 0.09). These results suggest that
      castration induces plasticity in the alpha 1-adrenoceptor subtypes involved in
      the contractions of the aorta to noradrenaline.

PMID- 14567073
TI  - [Sensorineural hearing loss due to neonatal hyperbilirubinemia].
AB  - In this article, the sensorineural hearing loss is presented as a possible
      sequelae of neonatal hyperbilirubinemia. In our program of early hipoacusia
      detection, 241 babies were examined from January 1996 until November 1999; 7
      cases had a history of hyperbilirubinemia in the neonatal period and 2 of them
      were diagnosed of sensorineural hearing loss. We discuss how the bilirubin or any
      other associated factor might have been the cause and this could explain the
      selective affectation of some children.

PMID- 14567074
TI  - [Disability in patients with benign paroxysmal positional vertigo with posterior
      semicircular canal involvement].
AB  - OBJECTIVE: The aim of this work is to analyze the vestibular function and level
      of disability in two populations of patients with positional vertigo but with
      different results in the Dix-Hallpike test. MATERIAL AND METHODS: 114 patients
      were assessed. In 65 the Dix-Hallpike test was positive (DH+) and in 49 negative
      (DH). The caloric test was performed as well as the assessment of disability with
      the pertinent questionnaires for vestibular disability. RESULTS: Patients in the
      DH+ group showed a higher level of disability in the physical subscale of the DHI
      and a higher perception of a deteriorated quality of life. Patients in the DH-
      group showed a more severe disability in the emotional subscale of the DHI.
      CONCLUSIONS: Once the phenomenon of nystagmus fatigability is ruled out, patients
      with positional vertigo and DH- must not be considered a minor form of positional
      vertigo.

PMID- 14567076
TI  - [Intranasal approaches for pituitary area tumors. Our experience].
AB  - Transsphenoidal approach is the most commonly employed surgical technique for the
      resection of pituitary tumors. We present our experience in the transnasal
      transsphenoidal approach in 30 patients undergoing pituitary surgery from 1998 to
      2002. Ten patients underwent surgery via a sublabial-transeptal-transsphenoidal
      approach, 15 patients via a transeptal-transsphenoidal approach and 5 patients
      via a pure endoscopic transnasal-transsphenoidal. The pathological study showed
      29 pituitary adenomas and 1 Rathe's cleft cyst. We conclude that the pure
      endoscopic transnasal-transsphenoidal approach guided by a navigator-system is
      safest and more effective approach. We reserved the transeptal-transsphenoidal
      approach for cases with obstructive septal deflection and poor pneumatized
      sphenoid sinuses. We do not recommend the use of the sublabial-trans-sphenoidal
      approach.

PMID- 14567075
TI  - [The role of video-nystagmography in the diagnosis of acoustic neuroma].
AB  - AIM: Schwannoma of the vestibular nerve represents 75% of all expansive processes
      affecting the pontocerebellosum angle. Hearing loss is the most frequent symptom
      at diagnosis (86%) with or without tinnitus, in the intracanalicular tumors.
      Vestibular symptoms are described in 60% of patients. MATERIAL AND METHOD: We
      study twenty cases of acoustic neuromas diagnosed between years 2000 and 2002 in
      both Otolaryngology and Neurosurgery Departments in our hospital.
      Videonystagmography (VNG) was performed in all of them. Videonystagmographic
      findings were analyzed statistically together with the tumoral size and
      hypoacusia level. DISCUSSION AND CONCLUSION: According to the medical literature
      reviewed for this paper, we conclude that caloric tests are the most frequently
      altered ones (77%), showing vestibular hyporreflexia or arreflexia.

PMID- 14567077
TI  - [Osteoplastic flap: our experience].
AB  - OBJECTIVE: Despite the advances of endoscopic surgical techniques, the frontal
      sinus obliteration via the osteoplastic flap (OPF) remains the treatment option
      for frontal sinus pathologies. The aim of this study is to evaluate indications,
      procedures and results of this technique. MATERIAL AND METHODS: Retrospective
      study of thirty one patients that underwent OPF procedure between 1986 and 1999.
      RESULTS: The average patient's age was 42 years. The treated pathologies were: 12
      mucoceles, 8 fractures, 4 osteomas, 4 sinutisis, 1 frontal abscess, 1 frontal
      osteomielitis and 1 orbital celullitis. The main clinical symptoms were headache
      (32%) and nasal obstruction (29%). The surgical approaches es used were: brow
      incision in 24 patients (78%), bicoronal in 5 (16%) and through the frontal wound
      in 2 traumatic cases (6%). Endonasal surgical procedures were associated in 8
      patients (25%). Frontal sinus obliteration was performed in 23 patients (74%).
      Surgical revision was necessary in two cases. The were no serious complications.
      The overall esthetic and functional outcome was good. CONCLUSIONS: OPF with fat
      obliteration is an useful technique in patients who had frontal sinus disease
      refractary to other methods.

PMID- 14567078
TI  - [Endoscopic sinus surgery. A review of 1,093 cases].
AB  - We present a serie of 1,093 patients that underwent, along 10 years, endoscopic
      surgery due to paranasal sinus pathology in a third level hospital. The technique
      used is described, the long term results analysed, as well as the minor and major
      complications specially the CSF fistulas and their cause.

PMID- 14567079
TI  - [Treatment for the early stages (T1-T2NO) of squamous cell carcinoma of the
      mobile tongue].
AB  - OBJECTIVE: The aim of this study is to define the best local treatment in
      patients with squamous cell carcinoma of mobile tongue in the early stages (I-II)
      and to establish the best election for neck management. MATERIAL AND METHODS: We
      evaluated 90 patients classified as stage I and II between 1984 and 1999. Sixty
      eight patients out of the ninety (75%) were treated with radio-therapy and twenty
      two (25%) with surgery. Neck dissection was used in 39% (35/90) of patients.
      RESULTS: The rates of ultimate local control for T1NO lesions were similar for
      both treatment groups (94% vs. 95%). For T2N0 lesions the ultimate local control
      did improved in those patients treated with surgery (100%) compared to those that
      had radiotherapy (77%). Regional control was better in the group that underwent
      neck dissection compared to the group that had just ganglionar control (89% vs.
      79%). CONCLUSIONS: We recommend local surgical treatment for T1-T2NO and in our
      experience prophylactic treatment of lymph nodes leads to a better regional
      control.

PMID- 14567080
TI  - [Diagnosis and antimicrobial treatment for sinusitis].

PMID- 14567081
TI  - [Riedel's thyroiditis: a report of a case with fatal outcome].
AB  - The Riedel's thyroiditis is a chronic inflammatory disease of the thyroid gland
      characterized by a process of fibrosis that destroys the gland partially,
      extending to the adjacent cervical structures. Its origin is unknown, although
      there are several theories in this respect. The clinical manifestations are not
      specific and it confuses frequently with neoplasia or infection, like a hard and
      painless thyroid mass that causes compressive symptoms. In this work, we report a
      case with lethal outcome.

PMID- 14567082
TI  - [Brown bone tumor as the first manifestation of primary hyperparathyroidism].
AB  - We report a clinical case of a 26 years old female who had a 2 years evolution
      chin tumour with hypercalcemia (11.8 mg/dl) and PTH (paratohormone) of 761 pg/ml.
      She underwent a CT scan and MRI of the mandible, as well as a biopsy followed by
      excision of the tumour by the maxilofacial surgeons. Our ENT Department asked for
      a Scintigraphy (Tc99s-mibi) and thoracic-cervical CT, which showed a lesion that
      turned out to be an adenoma of the lower right parathyroid gland after surgery
      and pathological examination. The patient suffered a Primary hyperparathyroidism
      that was the main stimulus for the Brown Tumour made up by macrophagos and
      multinuclear giant cells, being this the first manifestation of the metabolic
      disorder. This form of hyperparathyroidism is very rare in the clinic. We do a
      literature review to establish the differential diagnosis for such pathology.

PMID- 14567083
TI  - [Current problems in pneumology].

PMID- 14567084
TI  - [Molecular genetics principles in cystic fibrosis. An example of genetic illness
      in pneumology].
AB  - The generalized exocrinopathy cystic fibrosis (CF) is caused by molecular lesions
      in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The basic
      defect of this autosomal-recessive disorder manifests in decreased permeability
      for chloride ions across the apical epithelial membrane. Of the more than 1,000
      known CFTR mutations the most frequent mutation F508del occurs on about 70% of
      North- and Mideuropean CF chromosomes. CFTR mutations are also causatively
      involved in male infertility, pancreatitis and several airway diseases like
      disseminated bronchiectasis. The differential diagnosis between CF, other CFTR
      opathies and diseases of unrelated etiology can be achieved by the assessment of
      clinical symptoms, CFTR mutation analysis and electrophysiological bioassays
      (sweat test, nasal potential difference, intestinal current measurements).

PMID- 14567085
TI  - [Chronic obstructive lung disease].
AB  - The chronic obstructive pulmonary disease (COPD) is one of the leading causes of
      morbidity and mortality worldwide. Recently, international guidelines for
      diagnosis, prevention and therapy have been published. Now also a modified German
      version of these guidelines is available. The diagnosis and the severity of the
      disease is established on the basis of spirometric findings. All stages of COPD
      are treated with bronchodilators (beta 2-sympathomimetics and anticholinergics).
      In addition, in stage II and III theophylline and inhaled corticosteroids may be
      used. Systemic steroids should be restricted to acute exacerbations. For patients
      with advanced COPD long-term oxygen therapy and in selected cases surgical
      procedures may be indicated. Rehabilitation measures are of high value.
      Strategies for primary prevention and smoking cessation programs are extremely
      important. To get to the diagnosis of COPD as early as possible, all smokers with
      cough and phlegm should undergo spirometry.

PMID- 14567086
TI  - [Bronchial carcinoma. Epidemiology, diagnosis and therapy].
AB  - Bronchial carcinoma still has a dark prognosis and therapeutic progress remains
      painfully slow: the 5-year survival rate raised in the last 20 years from 11 to
      15%. There are no early symptoms by the tumor and detection by screening is not
      effective. Worldwide incidence is raising, the falling rates in men in the
      western world have been compensated by a steep increase in eastern Europe an
      Asia. Cigarette smoking is in 85% the main cause of this epidemic. Better
      understanding of genetic predisposition may identify patients at higher risk.
      Tumor in stage IA-IIB of non small cell carcinoma could gain by neoadjuvant
      chemotherapy, what is more probable for stage IIA and IIIB. Radiation therapy in
      combination with chemotherapy improves survival in inoperable stage IIIB. In
      stage IV disease palliative chemotherapy is superior to best supportive care.

PMID- 14567087
TI  - [Pulmonary fibrosis. Classification, diagnosis, therapy].
AB  - A new classification of the idiopathic interstitial pneumonia has recently been
      proposed, defining idiopathic pulmonary fibrosis (IPF) more rigorously and in
      contrast to further subentities. The new classification is of prognostic and
      clinical relevance. Diagnosis requires a combined clinical, radiological and
      pathological effort. In patients with characteristic clinical and HR-CT findings,
      the diagnosis of IPF can be made with sufficient confidence without surgical lung
      biopsy. Recent evidence suggests that the primary pathogenetic event in IPF
      involves epithelial injury and abnormal wound heeling. This explains the
      ineffectiveness of the usual anti-inflammatory therapy in the majority of
      patients. Since no antifibrotic drugs are available at present, the recommended
      standard therapy is a combination of prednisone with azathioprine or
      cyclophosphamide. New antifibrotic molecules are already tested in clinical
      trials.

PMID- 14567089
TI  - [Cytogenetic changes and their prognostic significance in elderly acute myeloid
      leukemia].
AB  - Cytogenetic analyses were performed in 72 acute myeloid leukemia (AML) patients >
      or = 60 years old. Karyotype was normal in 35 (48.6%) patients (group III). 3
      patients (4.2%) had favourable karyotype with t(15;17) as an isolated aberration
      (group IV). 21 patients (29.2%) had adverse karyotypes (group I) and 13 (18%) had
      intermediate karyotypes (group II). Adverse karyotypes were simple (< 3
      aberrations), with add 3q, 5q-, 7q-, in 5 persons, and complex (> or = 3
      aberrations) in 16. Karyotypes of 14 patients from the latter group contained >
      or = 5 aberrations. Laboratory and clinical data were comparable between groups
      with > or = 3 and with > or = 5 changes. In more than 2/3 complex karyotypes
      chromosome 5 and 7 aberrations also were found. AML clinical course of group II
      patients was more similar to that of group I than of groups III and IV. A
      frequency of complete remissions differed statistically between group I and the
      others and a frequency of complete and partial remissions together--between I +
      II and III + IV groups. Overall survival time differed statistically between all
      groups. There were significantly more patients with secondary AML in groups I and
      II than in group III. Analysis according to FAB did not show prognostic
      significance of this classification. Authors conclude that cytogenetics have a
      fundamental prognostic importance in AML of the elderly and should be taken into
      account in establishing therapeutic strategies.

PMID- 14567090
TI  - [Activated protein C resistance, Leiden mutation, anticoagulant proteins and
      fibrinogen levels in patients with deep venous thrombosis].
AB  - Resistance to activated protein C (APC-R) is the leading cause of deep vein
      thrombosis (DVT). Deficiencies of protein C (PC) or its cofactor protein S (PS)
      are less frequent. Resistance usually results from nucleotide substitution (1691
      GA) in the factor V gene (Leiden mutation). We searched for APC-R and the Leiden
      mutation (FVL) and measured the activities of PC, PS, antithrombin III (AT III)
      and Fb levels in patients with DVT. The results were analyzed against a history
      of thrombosis (idiopathic, risk factor related). We enrolled 29 patients aged 50
      years or younger, with first symptoms of thrombosis detected before the age of 40
      years. The control group consisted of 25 healthy volunteers of similar age. APC-R
      was established using Accelerimat (bioMerieux) assays. APC-R was diagnosed when
      the normalized sensitivity coefficient "r" was < 0.9. FVL was detected with the
      SSP-PCR (sequence specific primers-polymerase chain reaction) method. Abnormal
      APC-R "r" values were found in seven DVT patients (24%). Heterozygous (G/A
      genotype) form of the Leiden mutation was confirmed in six of them (all had a
      history of recurrent thrombosis). FVL carriers demonstrated lower PC levels in
      comparison with controls and DVT without FVL. Eight patients (27%) had PS
      activities below the cut-off point (60%). The deficiency in six of them was not
      associated with other abnormalities. Patients with recurrent thrombosis had
      markedly higher concentrations of Fb (usually without FVL) and reduced AT III
      activities. The study has shown that the APC-R test is useful for FVL screening.
      The Leiden mutation, elevated levels of Fb and reduced activities of PC are the
      main factors predisposing to DVT and its recurrence. Reduced activity of PS is
      usually an isolated abnormality tending to predispose to a single DVT episode.

PMID- 14567088
TI  - [Community-acquired and nosocomial pneumonia].
AB  - Mortality of pneumonia is low in the outside setting (1%) but rises up to 20% in
      hospital admitted patients. Early diagnosis and standardized therapy improve
      patient's prognosis. For community acquired pneumonia age, comorbidity and the
      setting of therapy (outside department, normal ward or intensive care unit) are
      the most important variables to choose an adequate antibiotic treatment. For
      nosocomial pneumonia risk stratification is according to severity of illness,
      length of hospital stay and antibiotic pretreatment. In the outpatient setting a
      7-day monotherapy is mostly successful. In severe illness the combination of a
      betalactam antibiotic with a new fluorchinolon seems to be superior to an
      aminoglycosid therapy. Antibiotic resistance due to mistakes in antibiotic
      therapy is an increasing problem in the intensive care unit. Therefore, pneumonia
      preventive measures like influenza and pneumococcal vaccination become more
      important. Standardized hygienical procedures help to reduce nosocomial, mainly
      ventilator associated pneumonia.

PMID- 14567091
TI  - [The impact of plant-sterol supplemented diet on the LDL and oxidized-LDL levels
      in young men].
AB  - As evidenced by clinical trials, sterols and stanols may reduce LDL-cholesterol
      more potently than the restriction in the dietary intake of saturated fatty acids
      and cholesterol. So far, in Poland no clinical trials on the preventive
      applications of plant sterol margarines were conducted. Therefore, the objective
      of our study was to confirm their utility in primary prevention of cardiovascular
      disorders in young, healthy men who habitually consume butter. The present study
      was conducted on 42 healthy men (24.5 +/- 6 yr)--priests students living
      throughout the study in a boarding house and 4 weeks consumed during the study
      the same amounts (portions) of all diet elements, and the only difference were
      the two compared fats used in the study. 31 men consumed daily 15 g of extra
      butter (30 g/d), and 31 men consumed twice daily 15 g of margarine (30 g/d) with
      the addition of plant sterol esters amounting to 8 g/100 g of the product. Total
      cholesterol reduction by 7% (p < 0.001), and above all the LDL reduction by as
      much as over 11% (p < 0.001) confirm the beneficial effect of sterols on lipid
      parameters. The first time we observed reduction of oxidized LDL (oxy-LDL) by as
      much as 21% (p < 0.001) after consumption of margarine with plant sterol. This
      results suggest that sterols have pleiotropic effects, similar to statins. Our
      proposal of this results is that sterol have anti-inflammatory effect,
      probability by reduction of oxysterols from food. Of note is the fact that
      dietary sterol intake did not cause any changes in the HDL fraction level. Also
      the observed reduction in the atherogenic index (LDL-C/HDL-C) by over 11% (p <
      0.001). On the other hand, the disadvantageous effect of butter-containing diet
      on blood serum lipids, with a trend towards their increase, was confirmed in the
      present study. The results obtained indicate a potent hypolipaemic activity of
      dietary sterol intake in normocholesterolemics young men, and probably that is
      the one of the important methods of prevention heart disease.

PMID- 14567092
TI  - [Serum aminoterminal peptide of type III procollagen (PIIINP) and transforming
      growth factor-beta1 (TGF-beta1) levels in patients with chronic hepatitis B and
      C].
AB  - Fibrosis is the process accompanying majority of chronic diseases of liver,
      independent of etiological factor and leading to cirrhosis and hepatic failure.
      Monitoring fibrosis process by liver's biopsy is limited, so many attempts are
      undertaken to assess concentrations of definite proteins in blood, which could be
      easily accessible marker of intrahepatic process. It seems, that among others,
      determinations of blood concentration of aminoterminal propeptide of procollagen
      III--index of collagen's III synthesis and TGF-beta 1--cytokine of
      antiproliferative action and inhibiting hepatocytes' growth, yet inducing
      fibroblasts' growth and stimulating fibrosis process brings out such a
      possibility. The aim of the study was simultaneous determination of TGF-beta 1
      and PIIINP concentration in blood of patients with chronic hepatitis B and C
      before interferone's therapy in comparison to healthy controls, assessment of the
      parameters in dependence on stage of liver fibrosis and determination of
      correlation between TGF-beta 1 and PIIINP. Studies were performed in 40 patients
      with chronic hepatitis B (CAH B) and 35 patients with chronic hepatitis C (CAH
      C). Significantly increased serum concentrations of TGF-beta 1 as PIIINP in both
      groups of patients (CAH B and CAH C; grading 2-3, staging 1-2) in comparison with
      control group was noted. Significant positive correlation of TGF-beta 1 and
      PIIINP serum concentrations in both groups of patients was observed. There was
      not significant changes in PIIINP serum levels in patients with hepatitis B and C
      in dependence on stage of liver fibrosis (staging 1 vs staging 2) but TGF-beta 1
      serum levels was significantly increased in CAH B and C patients with higher
      stage of liver fibrosis process. On the base of obtained results, it seems that
      changes in TGF-beta 1 concentrations in blood reflect "grading" and "staging" and
      can be a marker of intensification of intrahepatic fibrosis process whereas
      PIIINP levels in blood have rather the relation with "grading".

PMID- 14567093
TI  - [Menstrual disturbances and alternations in hypophyseal gonadal axis in end-stage
      premenopausal women undergoing hemodialysis: a multi-center study].
AB  - The results of the studies of hypophyseal-gonadal axis in dialysis women are not
      uniform. Mostly the increased serum concentrations of prolactine and pituitary
      gonadotropins are observed; the data about ovarian secretion are much more scanty
      and contradictory. The aim of this crossectional study was to assess changes in
      sexual hormones secretion and their associations with menstrual disturbations in
      premenopausal women with end-stage renal failure undergoing hemodialysis. Sixty
      three women from six mazovian dialysis units, aged 18-45 years (mean 35 +/- 7
      years) were enrolled into the study. They were divided into four groups according
      to their menstrual pattern: I--eumenorrhoea (n = 17), II--polymenorrhoea (n = 9),
      III--oligomenorrhoea (n = 16) i IV--amenorrhoea n = 21). There were no
      differences between both groups in respect to age, age of menarche, time on
      hemodialysis, and body mass index. In all subjects gynecological examination was
      performed and serum prolactin, FSH, LH, estradiol, progesterone and testosterone
      concentrations were assayed. In 49% women high serum prolactin concentrations
      were noted (the highest in group IV--1699 +/- 1022 vs 441 +/- 205 microIU/ml in
      group I; p < 0.05). Mean serum FSH and LH were increased in group IV only (33 +/-
      59 and 22 +/- 31 mIU/ml); no significant differences among groups examined were
      seen. Serum estradiol was increased in groups I-III (95 +/- 46, 72 +/- 33, and 83
      +/- 55 pg/ml, respectively) and decreased in group IV (27 +/- 22 pg/ml; p < 0.001
      in respect to remaining groups). Mean serum progesterone and testosterone
      concentrations were normal in all four groups, but serum progesterone was
      significantly lower in groups II-IV than in group I (p < 0.05). No differences in
      hormonal status between patients receiving and not receiving rHuEpo were
      observed. Menstrual disturbances are common (73%) in premenopausal women with end
      stage renal failure, with amenorrhea constituting a half of them.
      Hyperprolactinemia is the most frequently seen alteration in their hormonal
      profile with the highest concentrations in those with secondary amenorrhea.
      Increased serum gonadotropins and reduced serum estradiol concentrations are
      mostly seen in amenorrheic women, whereas in menstruating women serum estradiol
      is often slightly increased.

PMID- 14567094
TI  - [Interventional treatment of myocardial infarction. Own experience].
AB  - The aim of the study is the analysis of own results of myocardial infarction
      treatment using percutaneous coronary intervention (PCI) in the setting of twenty
      four hour long hemodynamic service. Between 01.12.1998 and 31.12.2001 249
      patients with diagnosis of acute myocardial infarction were admitted to our
      Department. Their mean age was 58 years, men -73.5%, median of pain duration was
      4 hours, diabetes occurred in 11.6%, hypertension in 37.3%, dyslipidemia occurred
      in 14%, smokers constituted 59% of patients. 60.2% of patients were in Killip
      class I, 18.5% in class II, 8.0% in class III and 13.3% in class IV. Anterior
      and/or lateral myocardial infarction was diagnosed in 105 patients, inferior
      and/or posterior in 144 patients. Angiography was performed in 225 patients, PCI
      was performed in 178. TIMI 3 flow was achieved in 76% of patients with shock and
      90% of patients without shock. Multivessel coronary artery disease was present in
      71% of patients. 30-day mortality in patients treated with PCI was 11.8%, after
      exclusion of III and IV Killip class patients mortality was 4.3%. 30-day
      mortality in group of patients with cardiogenic shock was 38.0%. Relative risk of
      death in patients in III and IV Killip class was higher for these treated
      conservatively: IV class -1.51 (p = 0.075), III and IV class (common group) -1.38
      (p = 0.064). In the year of 2001 30-day mortality among the patients in I and II
      Killip class treated with PCI was 2.43%. CONCLUSIONS: 1. Primary percutaneous
      coronary intervention in the treatment of myocardial infarction improves
      prognosis in group of patients with cardiogenic shock in 30-day observation. 2.
      11.8% mortality observed in our PCI treated group is associated in our opinion
      with occurrence of multivessel coronary disease in 71% of patients.

PMID- 14567095
TI  - [Severe thrombocytopenia associated with simultaneous cytomegalovirus and Epstein
      barr virus infection in an immunocompetence patient].
AB  - A 22 year old woman, without preceeding immunological and hematological disorders
      was hospitalized because of severe thrombocytopenia. The results of extended
      workup revealed simultaneous cytomegalovirus and Epstein-Barr virus infection as
      the most probable causative factor. Both, thrombocytopenia and the symptoms of
      viral infections resolved after consequent treatment with acyclovir,
      corticosteroids and intravenous immunoglobulines. Based on this original case
      report authors suggest the need of virological tests in newly diagnosed idiopatic
      thrombocytopenia.

PMID- 14567096
TI  - [Cholestatic hepatitis caused by prajmalium treatment: case report].
AB  - Prajmalium rarely causes idiosyncratic liver injury. Author describes the case of
      cholestatic hepatitis occurring in three weeks after cessation of short-term
      treatment with prajmalium. Eighteen months later, despite of good general status,
      physical and biochemical features of cholestasis were present. Pathologic
      examination of liver biopsy specimen revealed the chronic intracellular
      cholestasis with lymphocytic infiltration. Presented case indicate that even
      short-term treatment with potentially weekly hepatotoxic drug may cause the long
      term intrahepatic cholestasis.

PMID- 14567097
TI  - [Pulmonary histiocytosis X].

PMID- 14567098
TI  - [Serum proteins: clinical usefulness of determination and electrophoresis in
      various diseases].

PMID- 14567099
TI  - [Involvement of neutrophils in atherogenesis in diabetic patients with
      nephropathy].

PMID- 14567100
TI  - [Variability in the placebo values].

PMID- 14567101
TI  - [Physical activity in selected cancers prevention].

PMID- 14567102
TI  - [Platelet dysfunction in diabetes mellitus: the possibilities of prevention and
      treatment].

PMID- 14567103
TI  - [HIV infection--current challenges].

PMID- 14567104
TI  - [Economic aspects of ambulatory and inpatient treatment of HIV positive
      patients].
AB  - Highly active antiretroviral therapy (HAART) was introduced in the midst of the
      1990s. The sustained declin of morbidity and mortality by HAART has been proven
      to be cost effective despite high expenditures for regular administration of cost
      intensive antiretroviral drugs. Yearly direct treatment costs are estimated as
      high as [symbol: see text] 20,000 to [symbol: see text] 30,000 per case in
      Germany. Approximately two third of all direct costs are caused by the use of
      antiretrovirals. Despite rising use of HAART and increasing drug prices, general
      costs for treatment decreased in the last years. This is explained by declining
      costs for hospitalisation and by increasing use of less expensive drug
      combinations. In addition deferment of initiation of HAART to slightly more
      advanced stages of immunodeficiency is recommended in recent treatment guidelines
      and leads to further reduction of direct costs. Modified treatment concepts with
      presumed cost saving effects, like periods of antiretroviral treatment
      interruption, are currently under investigation.

PMID- 14567105
TI  - [HIV/AIDS Competence Network. An example for research networking in Germany].
AB  - Thanks to a nationwide network of specialized, clinic-associated outpatient
      facilities and competent registered physicians, the quality of care for HIV
      infected patients in Germany is high. Although basic HIV research is also well
      advanced in several centers, in contrast Germany's clinical HIV research is
      barely discemable on an international level. This deficit is primarily due to a
      lack of clinical studies involving patients from across the country and the fact
      that no national patient cohort system exists which could provide a basis for
      such clinical studies. The competence network HIV/AIDS aims to overcome this
      shortcoming by serving as a comprehensive, nationwide research alliance. The
      established patient cohort is linked to 13 projects. The infrastructure required
      for communications and data exchange will be based on a telematics platform.
      There will also be various service facilities established within the network,
      creating an organizational structure to promote the horizontal exchange of
      information between centers, as well as establish the vertical exchange of
      knowledge between physicians, patients, public health policy makers, and the
      general public.

PMID- 14567106
TI  - [Adverse effects of antiretroviral therapy. Aspects of pathogenesis].
AB  - Highly active antiretroviral therapy has resulted in remarkable reduction of
      morbidity and mortality of HIV infection. With increasing duration of therapy
      metabolic alterations such as hyperlipidemia, diabetes mellitus type 2 and
      lipodystrophy are encountered which considerably reduced quality of life for the
      patients. These adverse events are most likely due to protease inhibitors and
      nucleoside analogues with synergistic effects. The pathogenesis is related to
      metabolic alterations of the adipocytes with cellular insulin resistance and
      enhanced apoptosis of these cells caused by adipocytic cytokines such as
      adiponectin, leptin, TNF-alpha and interleukin 2. Switch of therapy regimens with
      elimination of the most suspicious substances and certain protease inhibitors can
      lead to improvement of deranged metabolism. Also symptomatic therapy is possible
      to cope with hyperlipidemia and diabetes, although no effective treatment is
      available to reverse already existing lipodystrophy. Our knowledge about the
      pathogenesis of these alterations might lead to new concepts and causal therapy
      in the future.

PMID- 14567107
TI  - [Status and current strategies of HIV vaccine development].
AB  - Despite intensive research efforts a vaccine against HIV has not yet been
      developed twenty years even after the onset of the HIV-epidemic. The problems in
      the development of an HIV-vaccine as well as former and current strategies to
      overcome these problems are presented here. The current status of human studies
      of different candidate vaccines is outlined.

PMID- 14567108
TI  - [Therapy of atrial fibrillation].
AB  - Atrial fibrillation is the most common cardiac arrhythmia in adults. Paroxysmal
      atrial fibrillation terminates spontaneously, whereas the persistent form
      terminates only after medical or electrical cardioversion. Permanent atrial
      fibrillation cannot be cardioverted. Restoration of sinus rhythm can be achieved
      by antiarrhythmic drugs or electrical cardioversion, both performed under
      continuous electrocardiographic monitoring. If atrial fibrillation has lasted
      longer than 48 hours or the precise time of onset cannot be determined, there are
      two alternative approaches: systemic anticoagulation to achieve an international
      normalised ratio (INR) of 2.0 to 3.0 for at least three weeks, followed by
      cardioversion; or cardioversion guided by transesophageal echocadiography
      indicating the absence of thrombus. Several drugs have been shown to be effective
      for the maintenance of sinus rhythm. Anticoagulant therapy is mandatory for a
      minimum of three weeks after cardioversion. In case of drug refractory, highly
      symptomatic atrial fibrillation the indication for radiofrequency catheter
      ablation should be discussed, although the value of this new method is still
      under evaluation.

PMID- 14567109
TI  - [15-year-old patient with decompensated heart failure and tachycardia with
      negative P-waves in inferior ECG recordings. An indication for heart
      transplantation?].
AB  - A 15-year-old girl was admitted with signs of severe cardiac failure. There were
      no symptoms of cardiac insufficiency 4 weeks before hospital admission. She
      presented with permanent supraventricular tachycardia with negative P-waves in
      leads II, III and aVF, the heart rate was 150 beats per minute. The
      electrophysiological examination showed a permanent junctional reentry
      tachycardia. A postero-septal accessory pathway could be eliminated successfully
      by radiofrequency catheter ablation. Immediately after the procedure cardiac
      function deteriorated with slight decrease of the strongly reduced cardiac
      output. Intensive care and application of dobutamine led to clinical stability.
      During a follow-up of two years the young patient showed permanent sinus rhythm
      and an age related physical strain. This case report documents the rapid and
      severe manifestation of cardiac failure owing to permanent junctional reentry
      tachycardia in a 15-year-old girl. She was referred for consideration of heart
      transplantation. Invasive electrophysiological treatment led to permanent sinus
      rhythm with improvement of left ventricular function.

PMID- 14567110
TI  - [52-year-old patient with subcutaneous space-occupying lesion in
      immunosuppression].
AB  - We report the case of a 52-years-old male patient, who was diagnosed with
      subcutaneous alveolar echinococcosis 6 months after liver transplantation for HCV
      related cirrhosis. Nether the explanted nor the transplantated liver revealed an
      echinococcus focus. Therefore a rare primary extrahepatic manifestation was
      likely. Interestingly, the echinococcal larvae had developed protoscolices. The
      development of mature tapeworms in human is a rarity, which could be related to
      the immunosuppressive therapy after liver transplantation. The patient was
      curatively treated by surgical removal of the subcutaneous tumor and a
      postoperative therapy with albendazole. Furthermore, HCV reinfection (genotype
      2b) was successfully treated with interferone alpha 2b and ribavirine for 6
      months.

PMID- 14567111
TI  - [Hypolipoproteinemias].

PMID- 14567112
TI  - [Phytotherapeutic medicines. A possible source of drug interactions].
AB  - Herbal drugs are popular. Coming from nature, many people are still reluctant to
      link them with the risk of adverse effects. Many of these products do not require
      a prescription. Thus, their use and any potential risks may easily escape the
      physician's attention. Interactions, causing either adverse effects or treatment
      failures, with synthetic drugs have attracted increasing interest and recent case
      reports (e.g. about patients suffering from transplant rejection upon using of St
      John's wort with subsequently insufficient cyclosporine levels) have triggered
      some systematic research. As of yet, however, a substantial part of knowledge is
      based on case reports only. In this situation, the assessment of potential risks
      arising from herb drug interactions is difficult. More research is needed. This
      review is a brief account of interactions involving garlic, ginkgo, ginseng,
      echinacea, and St John's wort.

PMID- 14567113
TI  - [Lowering cholesterol for prevention of myocardial infarct and stroke? MRC/BHF
      Heart Protection Study].

PMID- 14567114
TI  - [No wonder that today's medicine is so expensive!].

PMID- 14567115
TI  - [Concomitant ECG changes are more frequent].

PMID- 14567116
TI  - [Should one demonize IVF?].

PMID- 14567117
TI  - [The ART specialists respond to the ethical committee president].

PMID- 14567118
TI  - [Risks in medically-assisted procreation in case of positivity for HIV, hepatitis
      C virus or hepatitis B virus. The French law at the end of 2001].
AB  - Inclusion of HIV+, HCV+ or HBV+ couples in medically assisted procreation has
      been allowed by the French law since the publication of some legal texts dates
      January 12th 1999 and May 2001. This article tries to identify the viral risks of
      such inclusion and to analyse the answers given by the French law to eliminate
      these risks.

PMID- 14567119
TI  - [Fertility after hysteroscopic treatment of intra-uterine adhesions].
AB  - OBJECTIVE: The main aim of the study was to evaluate the efficacy of hysteroscopy
      in the treatment of intra-uterine adhesions with infertility. PATIENTS AND
      METHODS: This retrospective study of patients with uterine synechias treated
      exclusively hysteroscopically included 120 cases: 109 of them (90.8%) low
      fertility patients, 110 (91.7%) with menstrual disorders and 2 (1.7%) with no
      others symptoms. Mean age was 34 years (range: 21-45 years). Operative
      hysteroscopy was performed in 155 cases including electrosection in 124 cases
      (80%) and a collapse in 31 cases (20%). A single endoscopic procedure was
      performed in 96 patients, 2 procedures in 17 patients, 3 in 3 patients and 4 in 4
      patients. Mean follow-up was 26.8 months (range: 6-52 months). RESULTS: Good
      anatomic results were achieved in 116 patients (96.7%) after 1, 2 or 3
      hysteroscopic procedures. We obtained good results in 58.2% of the patients with
      menstrual disorders. One pregnancy was achieved in 49 of patients (44.9%)
      including: 35 childbirth, 13 abortions and 1 molar pregnancy. DISCUSSION AND
      CONCLUSION: Hysteroscopy, easy procedure, allowing reproducible treatment with
      low morbidity should be proposed as first intention treatment in all cases with
      synechia. Fertility prognosis is tightly related to the gravity of synechia and
      its topography.

PMID- 14567120
TI  - [Abruptio placentae: epidemiological, clinical and prognostic aspects with
      respect to a 177 case series].
AB  - OBJECTIVE: A retrospective study based on 177 cases of abruptio placentae, and
      describing the epidemiological, clinical and prognosis aspects. PATIENTS AND
      METHODS: A hundred and seventy-seven cases, corresponding to 185 children, were
      registered over a five-year period in the department of gynecology and obstetrics
      of the CHNYO of Ouagadougou. RESULTS: Abruptio placentae occurrence rate was
      about 9.6 per 1000 deliveries. In our study, this type of accident was most
      frequent with 30 to 34-year-old women (31.1%), with multiparous ones (56.5%), and
      with those suffering from arterial hypertension linked to pregnancy (31.1%). The
      clinical picture was most often complete, 83.1% of patients having reached grade
      3 of abruptio placentae with complete symptomatology and foetal death. Vaginal
      delivery was preferred to cesarean section in 64.4% of the cases. Maternal death
      rate was about 3.9% and mainly caused by severe anemia (61.6%) and puerperal
      infections (7.9%). Foetal prognosis was dominated by the high rate of
      mortinatality (85.9%). DISCUSSION AND CONCLUSION: To reduce maternal mortality as
      well as morbidity due to abruptio placentae, correct prenatal follow-up, early
      diagnosis and prompt evacuation of the womb are required.

PMID- 14567122
TI  - [The prescribing of CA 15.3 in the Roubaix health insurance district].
AB  - OBJECTIVE: Appreciate medical practice concerning CA 15.3 indications. MATERIAL
      AND METHOD: Starting with dosages reimbursed to people on social security, the
      health service near the primary Health care assurance offices (caisse primaire
      d'assurance maladie) at Roubaix, conducted a study over a period of 3 months, in
      which they asked physicians for their reasons for prescribing CA 15.3. RESULTS:
      Of the 205 questionnaires at their disposal, only 58 prescriptions conformed to
      the guidelines (28.3%). Prescriptions from specialists conformed in 48.9% of
      cases, as opposed to 12.8% from general practitioners. DISCUSSION AND CONCLUSION:
      The estimated assessment of the immediate additional expenditure will be shown to
      be 4 million Euros a year, over the whole of France.

PMID- 14567121
TI  - [Comparison of changes in biochemical markers of bone turnover after 6 months of
      hormone replacement therapy with either transdermal 17 beta-estradiol or equine
      conjugated estrogen plus nomegestrol acetate].
AB  - OBJECTIVE: To compare changes in biochemical markers of bone turnover in
      postmenopausal women who received sequential discontinuous hormone replacement
      therapy (HRT) with either transdermal 17 beta-estradiol gel (group 1) or oral
      equine sulfoconjugated estrogen (group 2), plus nomegestrol acetate. PATIENTS AND
      METHOD: Prospective, open, randomized, controlled trial, conducted on 3 parallel
      groups of 106 postmenopausal women. All treated groups received estrogen therapy
      for 25 consecutive days every month. The estrogen used was either 1.5 mg/day of
      transdermal 17 beta-estradiol gel (group 1) [N = 42, average age (AA) = 51.6
      years, average duration of menopause (ADM = 21.5 months)], or 0.625 mg/day of
      oral equine sulfoconjugated estrogen (group 2) [N = 39, AA = 51.3 years, ADM =
      16.8 months]. In all cases nomegestrol acetate 5 mg/day was added for 12
      consecutive days every month. The control group comprised 25 patients, [AA = 53.4
      years, ADM = 33.7 months]. Two bone resorption markers: urinary cross-linked N
      telopeptide and C-telopeptide of type I collagen (U-NTX/Cr, U-CTX/Cr), and a bone
      formation marker: serum bone specific alkaline phosphatase activity were measured
      before and 6 months after treatment start. RESULTS: Significant decreases from
      baseline values were observed for the 3 biochemical markers in both treated
      groups compared with control (P < 0.001). There were no significant differences
      in changes between the 2 treated groups for the 3 biochemical markers. The mean
      percentage change in the 3 biochemical markers was: from -9.3 to -45.5% in group
      1, from -20.5 to -39% in group 2, and from -3.3 to 2% in control group. In group
      1, the mean percentage decreases in U-CTX reached optimal threshold of bone
      turnover change (-45%) which is considered by the International Osteoporosis
      Foundation as clinically relevant because it predicts an increase in BMD greater
      than 3% when treatment is maintained over a long term. DISCUSSION AND CONCLUSION:
      Both treated groups induced a significant comparable decrease of bone turnover
      markers after 6 months of intervention, compared with control. The group treated
      with cyclic administration of transdermal 17 beta-estradiol (1.5 mg/day) and
      nomegestrol acetate (5 mg/day) showed a bone resorption markers decrease
      corresponding to the threshold of clinical relevance described in the
      international literature and predictive of positive BMD response in long term.

PMID- 14567123
TI  - [Pseudotumoral tuberculosis of the cervix].
AB  - Cervical tuberculosis is a rare pathology, which can clinically look like a
      cervix cancer. The biopsy re-establishes the right diagnosis. The treatment is
      medical. The prognosis is primarily the infertility due to frequent associated
      general genital tuberculosis.

PMID- 14567124
TI  - [Paraquat poisoning at the beginning of pregnancy].
AB  - Case report of a paraquat poisoning at the beginning of pregnancy (10 weeks) with
      mother and child survey. The baby was exempt of abnormalities and of normal
      weight. He was followed up to the age of 4 and did well clinically. These data
      are associated with a review of the literature.

PMID- 14567125
TI  - [Information given orally. The position of the psychologist].
AB  - As important as a precise diagnosis and an appropriate treatment, the words which
      the doctor is going to tell to the sick child and his family will have a
      determining therapeutic effect on the evolution or the regression of the disease.
      The present article illustrates this comment through histories lived in an
      intensive care unit of a Paris hospital.

PMID- 14567127
TI  - [Computerized tomography pelvimetry: recent advances].
AB  - We describe a new technique of pelvimetry by computerized tomography (CT), using
      multislice-CT. This new technique can provide measurements of the classical
      diameters and is able to bring new informations on anatomical aspect of the bony
      pelvis, especially of the superior strait, with images easier to understand by
      obstetricians and midwives. It is a simple technique to perform, without
      increasing cost. No additional irradiation is needed, but this point has to be
      confirmed by multicenter evaluation.

PMID- 14567126
TI  - [Surgical treatment for endometrial adenocarcinoma: first approaches. Review of
      the literature].
AB  - Three surgical approaches have been described for the treatment of women
      presenting an endometrial cancer. The aim of this study was to appreciate the
      current criteria that would offer guidelines for this choice. We reviewed the
      data available in the literature (search Medline). Only laparotomy and
      laparoscopy permit the carrying out of all the routine surgical staging according
      to the FIGO's criteria (classification 1988). Only one randomised study compares
      the results obtained by laparotomy and laparoscopy. Laparoscopy patients had
      significantly less morbidity. Overall survival did not differ in both groups with
      a limited follow-up. The other not randomised studies show that laparoscopy is
      usually proposed to patients having a lower IMC and presenting limited stages. No
      randomized study had compared laparotomy with the only vaginal surgery. The
      latter is generally proposed for patients having an associated comorbidity and
      presenting limited stages. In such cases, no difference in survival is
      highlighted. Obesity does not represent an absolute contra indication for any
      way. It makes the surgery generally more complex. A suspicious ovarian lesion, a
      large uterus are, currently, an indication for laparotomy. Laparoscopy can be
      accepted only if the uterine volume is lower than 500 g and without deep
      myometrial infiltration. Laparotomy surgery is the standard. The main indication
      of vaginal surgery is to permit treatment to high operatory risk patients.
      Laparoscopy is an option for the early stages. It is not recommended if an
      ovarian lesion or a deep uterine parietal infiltration are suspected. Whatever
      the route used, the surgeon must be trained.

PMID- 14567128
TI  - [Umbilical hernia. New repair technique with a minimal scar].
AB  - OBJECTIVE: Describe a surgical technique concerning the treatment of umbilical
      hernias that have a diameter less than 5 cm, with a reduction of scars. PATIENTS
      AND METHOD: After analysing the different techniques of umbilical hernias repair,
      the authors suggest a new personal technique. The surgical treatment consists in
      removing the hernia sack after double M incision of the umbilical skin, repairing
      the abdominal wall by Quenu technique, folding the abdominal muscles and
      reconstructing the umbilicus. RESULTS: The results, which are achieved on nine
      patients, with check up two years after, confirm the validity of the technique.
      DISCUSSION AND CONCLUSIONS: The scars after umbilical hernia surgical treatment
      are very important and visible because of their being located on the middle line
      of the abdominal wall. For the female patient in particular, this scar represents
      a great psychological annoyance. The double M technique leaves only an invisible
      scar with a good functional result.

PMID- 14567129
TI  - [What kind of reconstruction after mastectomy? Immediate reconstruction].

PMID- 14567130
TI  - [What kind of reconstruction after mastectomy? Different reconstruction].

PMID- 14567131
TI  - [Breast feeding: implementation and continuation through the first six months of
      life. Recommendations (May 2002)].

PMID- 14567132
TI  - [The pediatrician of maternity: a threatened species I. de Montgolfier-Aubron et
      F. Gold. Gynecol Obstet Fertil 2002; 30:841-4].

PMID- 14567134
TI  - Neuroaugmentation for chronic pain. Preface.

PMID- 14567133
TI  - [Uterine morcellation during vaginal hysterectomy: apropos of a series of 216
      prospective cases. B. Deval et al. Gynecol Obtet Fertil 2002; 30:850-5].

PMID- 14567135
TI  - History of neuroaugmentative procedures.
AB  - Neuroaugmentation, the use of chronic stimulation of the brain and spinal cord
      for pain management, developed during the past 30 years. It evolved, however,
      from concepts of pain treatment that were based on observations and clinical
      experience dating back an additional two decades or more. The appreciation of the
      role of the extralemniscal system and descending influences from the brain in
      modulation of pain perception led to the Melzack-Wall gate theory. The concept
      proposed in that theory, that pain perception could be lessened by increasing
      activity in neural structures not associated with pain, led to chronic
      stimulation of deep brain and spinal cord as a modality for the management of
      chronic pain. Both brain and spinal structures emerged as targets for
      neuroaugmentation.

PMID- 14567136
TI  - Evaluating the complex chronic pain patient.
AB  - The evaluation of the complex chronic pain patient should be different than for
      the patient with a simple pain problem. The former requires a team approach. It
      is important that the neurosurgeon contemplating a pain-relieving operation get
      the best information that is likely to have an impact on outcome. This should
      include the following: 1. Some way to extract the appropriate information
      contained in the patient's medical records. 2. Physical factors that have a
      negative impact on prognosis. 3. Psychologic information, including return-to
      work decisions, medication use issues, meaning of prior successes, negative
      environmental factors, codependency issues, secondary gains and their impact,
      presence of pain games, negatively acting financial considerations, impact of
      depression, presence of poor role models, impact of pain on general functioning,
      and the patient's future plans. Consider that just like a successful operation is
      a symphony of relatively simple harmonious parts, so, too, is the assessment of
      the complex chronic pain patient. The complexity of the patient and her or his
      predicament should not impair your ability to understand her or his real needs.
      The appropriate assessment of the patient requires that issues other than the
      pain itself be factored into the decisions about interventions. In the end, it is
      not appropriate to suggest afterward that psychosocial factors were the major
      cause for a poor result when nothing had been done about the same factors that
      had been present before the procedure.

PMID- 14567137
TI  - Mechanisms of action of intrathecal medications.
AB  - Intrathecal delivery of medications for the management of chronic pain syndromes
      reflects a modern targeted delivery system with the potential for even greater
      efficacy than is outlined in Tables 1 and 2. The twentieth century ushered in the
      development of parenteral approaches of medical therapy for chronic pain and
      other diseases that were superior to the traditional oral delivery methods known
      in the preceding century. Targeted drug delivery represents a significant
      advancement in the treatment of patients with chronic pain and is likely be the
      method of choice for the twenty-first century. This method of delivery is best
      represented by current drug delivery systems, such as the intrathecal drug pump.
      Traditional pharmacologic agents will still be used in the twenty-first century;
      however, the development of novel compounds, transplanted tissues, and genetic
      engineering will likely usher in a new era of pain management, including their
      use as analgesics for intraspinal infusion.

PMID- 14567138
TI  - Spinal cord stimulation: patient selection, technique, and outcomes.
AB  - Spinal cord stimulation, as with neuromodulation procedures in general, is a
      nondestructive, screenable, and reversible treatment option. Because there are no
      long-term side effects that have been reported; spinal cord stimulation is
      generally preferable as a first step when other less invasive treatments have
      failed to produce acceptable control of the pain.

PMID- 14567139
TI  - Intrathecal medication delivery.
AB  - This brief review of intrathecal pain medication delivery has emphasized the
      unusual but useful pharmacology of CSF drug delivery, the new study definitely
      showing that the method is helpful in cancer pain, and the rare complication of
      mass formation at the catheter tip. As new medications are developed for
      intrathecal delivery, this field is likely to expand, especially if a wider range
      of dorsal horn receptor mechanisms underlying pain processing can be modified.
      The changes in spinal cord signaling that are induced by chronic pain states are
      being investigated, and new possibilities for intervention are likely. the
      availability of a reliable well-understood way of delivering such new therapies
      by implanted drug pumps will speed the process. Intrathecal morphine for chronic
      pain has an important role in helping many patients with a wide variety of pain
      conditions and, as with all pain treatment, is woefully underused.

PMID- 14567140
TI  - Deep brain stimulation for the treatment of intractable pain.
AB  - Deep brain stimulation (DBS) plays an important role in the treatment of chronic
      pain when other less invasive treatment modalities have been exhausted. DBS is an
      apparently safe and effective treatment option for a select group of patients.
      Further research into the mechanisms of pain relief by DBS and careful
      prospective outcomes studies should help to define better the optimal techniques
      for DBS and clarify which patient populations may be best helped by this
      interventional procedure.

PMID- 14567141
TI  - Peripheral nerve neurostimulation.
AB  - There is a renewed interest in the use of PNS for the control of intractable pain
      caused by peripheral mononeuropathies and sympathetically mediated chronic pain
      syndromes. Technical advances in neurostimulation hardware, specifically lead
      design and surgical advancements with percutaneous and subcutaneous techniques,
      fuel this interest in part. The use of multipolar electrode arrays placed
      percutaneously in the region of peripheral nerves or in their dermatomal
      distribution without the need for extensive surgical dissection should help to
      support the use of PNS as a reasonable alternative to potentially destructive
      surgical procedures for chronic pain control.

PMID- 14567142
TI  - Psychologic evaluation for patients undergoing neuroaugmentative procedures.
AB  - Neuroaugmentative and neuromodulation therapy continues to expand. New
      applications are being found for existing technology, such as the use of SCS
      therapy in the treatment of head pain. The potential impact of existing therapies
      is enhanced by new discoveries as exemplified by the availability and
      demonstrated efficacy of different pharmacologic agents and combinations of
      agents in intrathecal therapy [39]. Increased attention is being paid to cortical
      stimulation, including motor cortex stimulation and deep brain stimulation. We
      must, however, not let our fascination for gadgets betray sound sense. The role
      of psychosocial factors in the outcome of more "objective" and measurable
      problems, such as spasticity and tremor versus pain, remains an open area of
      investigation. Although psychologic issues may not be as prevalent in the
      amelioration of such problems, they may influence the patient's overall level of
      satisfaction with the therapy and improvement in quality of life.

PMID- 14567143
TI  - Molecular biology and gene therapy in the treatment of chronic pain.
AB  - Technologic advancements have made cell type-specific targeting, expression
      control, and safe and stable gene transfer possible. Animal research has provided
      increasing experience with gene transfer to the nervous system and sensory
      neurons in particular. Gene-based neuromodultion can be achieved through neuronal
      delivery of transgenes capable of altering synaptic function. Alternatively, ex
      vivo gene transfer can be used to create cell lines capable of secreting
      analgesic neurepeptides. Translatation of these grafts and direct gene-based
      neuromoduation can be applied to the control of pain and the root causes of pain.
      These approaches combine anatomic and pharmacologic specificity. As the
      technology continues to improve, clinical application of cellular and molecular
      pain control is likely.

PMID- 14567144
TI  - Precentral stimulation for chronic pain.
AB  - A decade of clinical experience has suggested that precentral stimulation is an
      option for patients with deafferentation as well as other chronic pain syndromes.
      Permanent complications are uncommon. More scientific evidence is warranted to
      understand the precise mechanisms for this treatment modality. A larger organized
      clinical trial is desired to establish the efficacy of precentral stimulation.

PMID- 14567145
TI  - Anatomy and physiology of chronic pain.
AB  - Although much has been accomplished in the past several decades, treatment of
      chronic pain remains imperfect. This article presents the anatomy and physiology
      of the pain system along with the neurobiologic changes that occur in the
      establishment and maintenance of chronic pain states.

PMID- 14567146
TI  - Evaluation of body composition: practical guidelines.
AB  - The measurement of body composition in the truest sense allows for the estimation
      of body tissues, organs, and their distributions in living persons without
      inflicting harm. It is important to recognize that there is no single measurement
      method that is error-free. Furthermore, bias can be introduced if a measurement
      method makes assumptions related to body composition proportions and
      characteristics that are inaccurate across different populations. Some
      methodologic concerns include hydration of fat-free body mass changes with age
      and differences across ethnic groups [73]; the density of fat-free body mass
      changes with age and differences between men and women [74, 75]; total body
      potassium decreases with age [73] and fatness [76] and differences between
      African Americans and Caucasians [77]; the mass of skeletal muscle differences
      across race group [63]; and VAT differences across sex [78] and race [67, 79, 80]
      groups, independent of total adiposity. These between-group differences influence
      the absolute accuracy of methods for estimating fatness or FFM that involve the
      two-compartment model approach. The clinical significance of the body compartment
      to be measured should be determined before a measurement method is selected,
      because the more advanced techniques are less accessible and more costly.

PMID- 14567147
TI  - The prevalence of obesity.
AB  - During the past several decades, obesity has increased substantially, making it a
      true epidemic and a public health crisis that both health care providers and the
      public are going to have to face. Currently, 61% of the US population is
      overweight or obese and therefore at increased risk for a number of diseases that
      are associated with increased body fat. Indeed, the obesity epidemic already is
      leading to dramatic increases in type 2 diabetes and the metabolic syndrome.
      Almost a quarter of the population currently has metabolic syndrome, which places
      them at high risk for the development of coronary heart disease. The future of
      the general health of the US population depends on identifying and providing the
      best treatment and prevention strategies for obesity in the years ahead.

PMID- 14567148
TI  - Risks of obesity.
AB  - Obesity is a chronic disease in the same sense as hypertension and
      atherosclerosis. The cause of obesity is an imbalance between the energy ingested
      in food and the energy expended. The excess energy is stored in fat cells that
      enlarge or increase in number. This hyperplasia and hypertrophy of fat cells is
      the pathologic lesion of obesity. Enlarged fat cells produce the clinical
      problems that are associated with obesity, either because of the weight or mass
      of the extra fat or because of the increased secretion of free fatty acids and
      numerous peptides from enlarged fat cells. The consequence of these two
      mechanisms is other diseases, such as diabetes mellitus, gallbladder disease,
      osteoarthritis, heart disease, and some forms of cancer.

PMID- 14567149
TI  - Obesity: food intake.
AB  - This article discusses some of the changes in our food environment that have
      encouraged overeating and some research that underlies successful weight loss and
      maintenance of weight loss. The discussion of these topics will help in the
      guidance of patients to develop personalized eating plans and reduce energy
      intake, in part by recognizing the contributions of fat, concentrated
      carbohydrates, and large portion sizes.

PMID- 14567150
TI  - The menopause and obesity.
AB  - In summary, menopause tends to be associated with an increased risk of obesity
      and a shift to an abdominal fat distribution with associated increase in health
      risks. Changes in body composition at menopause may be caused by the decrease in
      circulating estrogen, and, for fat distribution shifts, the relative increase in
      the androgen-estrogen ratio is likely to be important. Clinicians need to be
      aware of the likelihood of weight gain during the perimenopausal and
      postmenopausal years because behavioral strategies for weight loss can be
      effectively used in this population. Weight loss or prevention of weight gain is
      likely to have significant health benefits for older women.

PMID- 14567151
TI  - The office approach to the obese patient.
AB  - Effective obesity care will not be accomplished without the implementation of a
      well-planned, office-based organizational system designed to address the
      assessment, evaluation, and treatment of the overweight and obese patient.
      Completing an office audit, as shown in Table 1, should be useful for triggering
      quality improvement opportunities regarding obesity care. Similarly, the chart
      audit in Table 4 can be used to assess current and future practice behavior. This
      article has reviewed the key office-based components for the delivery of obesity
      care. The strategies and techniques used for treatment are addressed in the
      remaining articles in this issue.

PMID- 14567152
TI  - Clinical evaluation of the obese patient.
AB  - Evaluation of the obese patient, like the evaluation of any medical patient,
      involves a medical history, physical examination, and laboratory evaluation. As
      with any chronic illness, there are certain aspects of the history, physical, and
      laboratory evaluation that deserve special emphasis. This article describes those
      aspects that deserve special emphasis in the case of obesity.

PMID- 14567153
TI  - Problems in childhood obesity.
AB  - Clearly, obesity prevention should be at the forefront of our approach to this
      epidemic problem and the goal of health care providers, public health officials,
      community, and families. The problems of the obese child are no longer solely
      those of increased risk for disease, but of disease itself. Health care providers
      are increasingly challenged to provide evaluation and treatment for the serious
      comorbidities and complications of obesity in childhood. Many of these
      comorbidities and complications are "invisible" and require careful and focused
      history and laboratory evaluation to elicit. Treatment of the complication and
      comorbidity should be focused on preventing progression, reversing the disease
      process, and, ultimately, achieving control of obesity with family-based
      lifestyle changes that will allow the child to maintain a healthy balance between
      his or her genetic predisposition and the environment.

PMID- 14567154
TI  - Behavioral techniques for treating the obese patient.
AB  - With more than 50% of American adults overweight or obese, primary care
      physicians should play an active role in helping overweight patients lose weight.
      Modest weight losses of as little as 7% to 10% can produce significant health
      benefits, such as preventing the development of diabetes. To help individuals
      achieve this weight loss, behavior change strategies should be emphasized with
      all overweight patients. Changes in diet and exercise can produce long-term
      weight loss with tremendous positive impact. Primary care physicians are well
      positioned to support these behavior changes in their overweight patients.

PMID- 14567155
TI  - Exercise strategies for the obese patient.
AB  - Exercise is an important component of weight-control programs, yet the impact of
      exercise for weight control is based on the ability of patients to engage in
      adequate levels of activity. The minimal level that should be recommended is at
      least 30 minutes of moderate-intensity physical activity on most days of the
      week. Although this level of physical activity may improve health-related
      factors, there is some evidence to support the recommendation of higher levels of
      exercise for weight-control purposes. The role of the clinician is to provide
      adequate guidance to patients regarding issues related to the intensity,
      duration, and mode of exercise that may be most appropriate. When addressing
      these issues, it is also important to consider the barriers that individual
      patients may encounter that will have an effect on adoption and maintenance of
      exercise behaviors.

PMID- 14567156
TI  - Use of sibutramine to treat obesity.
AB  - Medications are useful adjuncts to diet and exercise and may help patients lose
      weight and maintain significant weight loss (5%-10% from baseline). Pharmacologic
      approaches are indicated in those patients who have had prior weight-loss
      attempts, who have a body mass index greater than or equal to 30 kg/m2 or greater
      than or equal to 27 kg/m2 with comorbidity, and who are motivated and ready to
      undertake dietary and physical activity changes. This article provides a
      treatment algorithm to help physicians measure meaningful weight loss and
      proposes conservative blood pressure limits to guide the long-term prescription
      of sibutramine. Sibutramine can be a useful tool in the obesity treatment toolbox
      if used by knowledgeable practitioners.

PMID- 14567157
TI  - Orlistat in the treatment of obesity.
AB  - Orlistat has been well studied in several populations, including patients who do
      and do not have type 2 diabetes and in patients who have impaired glucose
      tolerance. Overall, modest, but significant, weight loss was seen in all three
      groups of patients with favorable effects on the comorbidities of obesity.
      Orlistat has not been associated with a serious adverse event profile, and the
      mild GI effects that are seen in some patients are well tolerated. In obese
      patients who do not have diabetes, weight loss is achieved and maintained as
      shown in the 2-year studies. Moreover, as was well documented in the Swedish
      multi-morbidity study, favorable treatment effects on the constituents of the
      metabolic syndrome are seen. Orlistat, together with a hypocaloric diet, was
      proven to be effective in preventing diabetes in patients who had impaired
      glucose tolerance. The addition of orlistat resulted in significant weight loss
      and significance decreases in levels of HbA1c in patients who had type 2 diabetes
      who were treated with antihyperglycemic drugs. Studies showed that it is possible
      to identify early which patients may respond best to treatment. Orlistat offers
      an attractive treatment option for obese patients who do and do not have diabetes
      and as a combination drug for treatment of obese patients who have type 2
      diabetes.

PMID- 14567158
TI  - Herbal preparations for obesity: are they useful?
AB  - The opportunities for additional research in this area are plentiful.
      Unfortunately, there has been relatively limited funding for research on herbal
      supplements compared with the amount of funding that is available for research on
      pharmaceuticals. Botanical dietary supplements often contain complex mixtures of
      phytochemicals that have additive or synergistic interactions. For example, the
      tea catechins include a group of related compounds with effects that are
      demonstrable beyond those that are seen with epigallocatechin gallate, the most
      potent catechin. The metabolism of families of related compounds may be different
      than the metabolism of purified crystallized compounds. In some cases, herbal
      medicines may simply be less purified forms of single active ingredients, but in
      other cases they represent unique formulations of multiple, related compounds
      that may have superior safety and efficacy compared with single ingredients.
      Obesity is a global epidemic, and traditional herbal medicines may have more
      acceptance than prescription drugs in many cultures with emerging epidemics of
      obesity. Several ethnobotanical studies found herbal treatments for diabetes, and
      similar surveys, termed bioprospecting, for obesity treatments may be productive.
      Beyond increasing thermogenesis, there are other biological rationales for the
      actions of several different alternative medical and herbal approaches to weight
      loss. For example, several supplements and herbs claim to result in nutrient
      partitioning so that ingested calories will be directed to muscle, rather than
      fat. These include an herb (Garcinia cambogia), and a lipid which is the product
      of bacterial metabolism (conjugated linoleic acid). Moreover, a series of
      approaches attempt to physically affect gastric satiety by filling the stomach.
      Fiber swells after ingestion and has was found to result in increased satiety. A
      binding resin (Chitosan) has the ability to precipitate fat in the laboratory and
      is touted for its ability to bind fat in the intestines so that it is not
      absorbed. In double-blind studies, however, this approach was found to be
      ineffective. There are two key attractions of alternative treatments to obese
      patients. First, they are viewed as being natural and are assumed by patients to
      be safer than prescription drugs. Second, there is no perceived need for
      professional assistance with these approaches. For obese individuals who cannot
      afford to see a physician, these approaches often represent a more accessible
      solution. Finally, for many others, these approaches represent alternatives to
      failed attempts at weight loss with the use of more conventional approaches.
      These consumers are often discouraged by previous failures, and are likely to
      combine approaches or use these supplements at doses higher than are recommended.
      It is vital that the primary care physician is aware of the herbal preparations
      that are being used by patients so that any potential interaction with
      prescription drugs or underlying medical conditions can be anticipated.
      Unfortunately, there have been several instances where unscrupulous profiteers
      have plundered the resources of the obese public. Although Americans spend $30
      billion per year on weight loss aids, our regulatory and monitoring capability as
      a society are woefully inadequate. Without adequate resources, the FDA resorted
      to "guilt by association" adverse events reporting, which often results in the
      loss of potentially helpful therapies without adequate investigation of the real
      causes of the adverse events that are reported. Scientific investigations of
      herbal and alternative therapies represent a potentially important source for new
      discoveries in obesity treatment and prevention. Cooperative interactions in
      research between the Office of Dietary Supplements, the National Center for
      Complementary and Alternative Medicine, and the FDA could lead to major advances
      in research on the efficacy and safety of the most promising of these alternative
      approaches.

PMID- 14567159
TI  - The management of the obese diabetic patient.
AB  - The prevalence of obesity and diabetes is increasing in the United States and
      worldwide. These diseases are predicted to explode to epidemic proportions,
      unless appropriate counteractive measures are taken. Several large studies (DCCT,
      UKPDS, Kumamoto) clearly showed that intensive glycemic control in the diabetic
      patient reduced microvascular complications and improved mortality. Despite this,
      the NHANES III showed that only 50% of diabetics have been able to achieve a
      HgbAic level that is less than 7%; this suggests the need for a re-evaluation of
      our approach to these patients. The management of the obese diabetic patient
      involves glycemic control and weight reduction. These goals are particularly
      difficult to achieve in the obese diabetic patient because progressive beta-cell
      dysfunction and increasing insulin resistance necessitates the administration of
      increasingly higher dosages of insulin, which, in turn, promotes weight gain. A
      vicious cycle may ensue. Lifestyle modifications with diet and exercise are an
      essential part of the management of the obese diabetic patient. These measures
      alone are often insufficient and concomitant pharmacologic therapy is usually
      required to achieve glycemic and weight control. Oral agents that improve
      glycemia, decrease insulin resistance, and limit weight gain are desirable.
      Because of the progressive nature of diabetes, glycemic control with monotherapy
      often deteriorates over time, which necessitates the addition of other
      pharmacologic agents, including insulin. When insulin therapy is required in the
      treatment of the obese diabetic patient, combinations with oral agents that have
      been shown to minimize the amount of exogenous insulin that is required, may
      minimize weight gain. In addition, the obese diabetic patient who is poorly
      controlled with maximum oral hypoglycemic therapy may benefit from weight
      reducing agents, such as sibutramine or orlistat. The introduction of these
      agents at other points in the management of the obese diabetic patients have been
      successful. Finally, for the severely obese diabetic patient, bariatric surgery
      may be the only effective treatment. Gastric bypass has been unequivocally shown
      to produce significant weight loss and improve glycemic control on a long-term
      basis in the obese diabetic patient. It is recommended that physicians avail
      themselves of all of these strategies in the management of the obese patient who
      has type 2 diabetes.

PMID- 14567160
TI  - [Survey of management methods for patients in a state of agitation at admission
      and emergency departments in France].
AB  - The increasing prevalence of the agitation states in the emergency department
      (ED) is a problem little studied on the epidemiological plan. OBJECTIVE: To
      define the prevalence of the agitation states in the ED in France, to determine
      predicative criteria of the agitation states to prevent a potentially dangerous
      situation and take care as fast as possible of it, to know current practices in
      front of these situations, and to collect the recommendations of the departmental
      managers of the ED to improve this management. METHOD: A questionnaire of
      appraisal was sent to the 464 managers of the ED of hospitals and clinics in
      metropolitan France, containing 21 questions. RESULTS: 137 (29.5%) departmental
      managers answered. The average of admittances by ED is 24,000 a year. The
      estimated prevalence of the number of situations of agitation represents 1.22% of
      the total of admittances. The average prevalence a month and by service of verbal
      attacks is 36.3, that of the physical attacks is 1.14. The number of attacks (and
      their consequences) correlate with admittances by ED. The intervention of the
      police is required on average 17 times a year and by ED. Only 29.5% of the ED
      consider to have premises adapted for the management of the agitated patients;
      32.3% of the ED have a protocol established for the agitation states; 16.3% of
      services accumulate a protocol and a training of the professionals; 10.5% of
      establishments have at the same moment adapted premises, a protocol and a forming
      of the staff for the management of the agitated patients. Among the agitated
      patients, those that profit by a sedation represent on average 67.7% and it
      varies according to ED. The sedative treatment used in first intention is
      loxapine in intramuscular injection for 84% of them. The predicative factors
      identified of agitation states are intoxications, mainly the alcohol (88%) and
      the poly drug addiction (46.3%). More than half of the ED recommend in a
      systematic way and for lack of diagnostic orientation the dosages of alcohol,
      drugs, glycaemia and bloody electrolytes; 85% of the departmental managers
      consider that a better management of the agitation states rests on the presence
      of adapted premises and on a specific forming of the nursing staff. CONCLUSION:
      The management of the agitated patients in the ED requires the placing of
      protocols and of specific trainings as well as of adapted premises. The major
      prevalence of attacks imposes realization of epidemiological studies and the
      priority placing of a coherent politics, considering the potential and often real
      gravity of these behavioural problems.

PMID- 14567161
TI  - [Seizure threshold and ECT. Importance for good clinical practice of ECT. A
      review of literature].
AB  - To induce a seizure for electroconvulsive therapy (ECT), an electrical charge is
      delivered above seizure threshold. The means and criteria used to determine the
      electrical dosage are subject to debate. Nonetheless this is an important issue
      because effectiveness and side effects have been shown to be influenced by the
      electrical charge used. The objective is to review data available in the
      literature on seizure threshold and ECT and determine the eventual consequences
      for practical determination of stimulus dosing. A comprehensive review of the
      literature is based on the search of electronic databases (Medline, INSIT) and a
      manual search; 72 references out of a total of 96 selected were used for this
      review. Seizure threshold varies widely between subjects receiving ECT (600% mean
      variation), however a majority of subjects of all ages have a threshold below 150
      mC. Only a few individuals have very high thresholds (400 to 800 mC). ECT has an
      anticonvulsive effect as threshold increases during a course of ECT. Many factors
      influence threshold and all are not known. Among those that have been documented
      are: the characteristics of the current used (longer stimulus duration with same
      dosage gives lower thresholds); electrode placement (bilateral gives higher
      thresholds than unilateral placement); age (explains 12 to 26% of threshold
      variance); gender (which inconsistently gives higher thresholds for males); and
      other factors such as anesthetic drugs, concurrent psychotropics, and some
      morphological characteristics. Different methods are used to determine an
      individually adapted dosage. Two are recommended: titration and age. The age
      method is based on the fact that age is an important factor influencing
      threshold. The titration method is based on the observation of a very important
      variation in threshold between individuals that is not explained by age. We
      discuss the pros and cons of each method.

PMID- 14567162
TI  - [French validation of the Verona Service Satisfaction Scale-VSSS-54F].
AB  - INTRODUCTION: The Verona Service Satisfaction Scale-French version (13) was
      translated and adapted from the Italian version of Verona Service Satisfaction
      Scale (27). The VSSS makes it possible to evaluate the satisfaction of people
      with serious mental illness with respect to the services. The original VSSS-54
      contained 7 dimensions: 1) Overall satisfaction, 2) Professionals' skills and
      behaviour, 3) Information, 4) Access to services, 5) Services efficacy, 6)
      Relatives' involvement and 7) Types of interventions. According to factorial
      analyses carried out by Ruggeri et al., the dimensions Information and Access to
      services were aggregated. However, no factorial analysis was carried out in order
      to verify the six dimension-structure of the VSSS. From an international
      perspective, the study entitled "The European Psychiatric Services: Inputs linked
      to Outcome Domains and Needs (EPSILON)" achieved the standardisation of different
      questionnaires in several languages (2). A new version of the VSSS entitled
      "Verona Service Satisfaction Scale-European version" (VSSS-EU) was developed and
      is now available in the following languages: Italian, Danish, German, English and
      Spanish. In order to compare in different countries the satisfaction of people
      with serious mental illness with respect to services, we undertook from 1998 to
      ascertain the psychometrical properties of the French version of the VSSS. (13).
      Confirmatory Factorial Analysis (CFA) was carried out on the six dimension
      structure of the VSSS-54F: 1) Overall satisfaction, 2) Professionals' skills and
      behaviour, 3) Information and Access to services, 4) Services efficacy, 5)
      Relatives involvement and 6) Types of interventions. For each dimension,
      consistency analysis (Cronbach's alpha) was computed in order to bring forth
      additional psychometrical properties of the VSSS-54F. METHOD:  PARTICIPANTS: 150
      clients involved in an intensive case management program and supported by 30
      mental health workers, filled out the VSSS-54F questionnaire. These clients were
      comprised of 110 women and 40 men, their ages ranging from 22 to 90 years (M =
      51.7, SD = 14.7). Among them, 65 (43.3%) had a diagnosis of schizophrenia or
      another form of psychosis, 56 (37.3%) had an affective disorder, 17 (11.3%) had
      anxious disorders and 7 (7.7%) other. DATA ANALYSES: Using the EQS Software (3),
      Confirmatory Factor Analyses (CFA) were carried out in this study. Thus, 'the
      evaluation of the models' fit with the empirical data was carried out by taking
      into account various statistical indices. In addition to the Chi square/df ratio,
      the indices of adjustment such as the "NonNormed Fit Index" (NNFI), the
      Comparative Fit Index (CFI), robust CFI (calculated starting from the Satorra
      Bentler Chi Square) as well as the RMSEA (Root Mean Standard Error of
      Approximation) were used to measure the fit of the models. Moreover, the
      estimation method "Maximum Likelihood-Robust" was carried out in order to
      evaluate the models. RESULTS: The original model with 6 dimensions (M1) does not
      present satisfactory fit indices. Indeed, the Chi Square/df ratio is above 2, the
      NNFI, CFI and CFI robust indices are lower than. 90 and the RMSEA is higher than.
      08. Most items from Types of intervention dimension presented saturation lower
      than.30, and consequently indicate that these items are not correlated
      significantly with their dimension. We notice also some correlations between
      error terms of the three items of Overall Satisfaction scale and other items of
      the VSSS questionnaire. Considering these last results and the direction taken in
      VSSS-EU by breaking down by profession items of Professionals' skills and
      behaviour scale, we obtained a new model (M2). The five dimensions of this model
      are as follow: 1) Psychiatrists/Psychologists' skills and behaviour (7 items), 2)
      Nursing staff/social workers' skills and behaviour (7 items), 3) Information and
      access to services (3 items), 4) Services efficacy (5 items), 5) Relatives'
      involvement (3 items). When we test this model, the fit indices are satisfactory:
      the Chi Square/df is 1.36, the NNFI, CFI and robust CFI indices are near or
      higher than 0.90, respectively 0.88, 0.89 and 0.94. Finally, the RMSEA index is
      0.08. In addition, the correlations between five dimensions are significant and
      vary from 0.58 to 0.87 (p < 0.05). The internal consistency coefficients for each
      new scale are all satisfactory, and vary from .83 to .91, except for the
      Information and access to services scales. But this latter finding shall be
      evaluated knowing that acceptable alpha can be close to .60 when scales count
      less than four items (16). CONCLUSION: This study confirms with some adjustments
      the factorial structure of the VSSS. The results indicate five dimensions (25
      items): Psychiatrists/Psychologists' skills and behaviour, Nursing staff/social
      workers' skills and behaviour, Information and access to services, Services
      efficacy, Relatives' involvement. Even if the Type of interventions dimension was
      not retained in the model, we suggest preserving it for eventual clinical
      evaluation based on each item. We also suggest, for future studies, the
      adaptation of the VSSS-54F to the European version, VSSS-EU. Indeed, the results
      of our study sustain the European version because the VSSS-EU is more focused
      since it separates the skills and behaviour of psychiatrists, psychologists,
      nurses and social workers (e.g. items 3a and 3b or items 22a and 22b). The next
      step in the validation process would be to measure Inter-rater and test-retest
      reliability as well as concurrent, convergent and discriminant validity of the
      VSSS-EU. Furthermore, a multicultural comparison of the VSSS-EU would be required
      if the instrument is used for interesting comparisons of survey.

PMID- 14567163
TI  - [Clozapine and pregnancy].
AB  - This article reviews the relations between clozapine and pregnancy. Six case
      reports are identified in the literature of pregnant patients who received
      clozapine. Novartis at Basle, Switzerland, through its pharmacovigilance and
      epidemiology, service, has data on nearly 200 cases summarized in this article.
      We also describe the case of a patient with paranoid schizophrenia who was
      hospitalized 10 times between the age of 22 to 32. She received clozapine when
      she was 29 years old and, with a daily dosage of 350 mg, she became asymptomatic.
      At the age of 33 and 37, she became pregnant and continued clozapine during her 2
      pregnancies. During her first pregnancy, she received insulin due to gestational
      diabetes associated with a body weight mass (BWM) of 30.4 (N = 20 to 25). During
      her second pregnancy, the BWM was 23.7 and she did not develop diabetes. She
      delivered at term 2 daughters who are at the time of this report 5 and 3 years
      old. The two girls are doing well and have no developmental delay. Psychotic
      symptoms exacerbation: the plasma concentration of clozapine diminishes during
      pregnancy due to a higher hepatic metabolism and distribution volume. Monitoring
      plasma concentration of clozapine can help to adjust its dosage. In case of
      psychotic symptoms exacerbation, the following can be recommended: 1) Increase
      the clozapine dosage; 2) Add a classic antipsychotic like perphenazine,
      trifluoperazine or haloperidol. Diabetes: obesity, glucose intolerance or a
      family history of diabetes are risk factors to develop gestational diabetes. The
      follow-up of patients, who take an atypical antipsychotic, should include
      constant monitoring of the blood glucose or Hb1A and lipid dosages. Complications
      at labor: Clozapine increases the secretion of oxytocine and the contraction of
      the uterine muscle. But, no studies can explain how clozapine affects the labor
      exactly. Some case studies report use of forceps, vacuum or cesarean.
      CONVULSIONS: Stoner (1997) described neonatal convulsions 8 days after birth. The
      mother was receiving 350 mg of clozapine, but also lorazepam and haloperidol
      during her pregnancy. The newborn withdrawal of lorazepam can increase the risk
      of convulsions and also haloperidol can diminish the convulsion threshold. Floppy
      infant syndrome: in the case described by Dimichele (1996), the mother received a
      daily dosage of 300 mg of clozapine and 2.5 mg of lorazepam 3 to 5 times a day.
      This can explain hypotonia. Stoner (1997) reports a second case where a mother,
      who received 600 mg of clozapine during pregnancy, gave birth to a child who had
      no convulsions neither hypotonia. DEVELOPMENT: The cases described concerning
      studies of children until age 2 to 3 years by Stoner (1997) and Dickson (1998)
      and until 6 years old by Barnas (1994), do not mention any developmental problem,
      similar to the two daughters of our patient. The pharmacovigilance service of
      Novarits reports 6% of malformations. But these reports must be considered with
      caution since they represent only the pregnancies reported spontaneously to the
      pharmaceutical company. This is only a portion of all pregnancies associated with
      clozapine. CONCLUSION: No specific risks for the mother and children can be
      attributed to the use of clozapine during pregnancy. However, the plasma
      concentration of clozapine is higher in the fetus compared to the mother (Barnas,
      1994); therefore, a minimal dosage should be used. Since clozapine is present in
      the maternal milk, breast feeding should be avoided. The advantages to use
      clozapine during pregnancy must exceed the risks. It is justified to continue the
      use of this medication even if data on classic antipsychotics (e.g.: haloperidol)
      are more extensive. Because the risk of psychotic exacerbation is higher, the
      substitution of clozapine is not recommended. The psychosocial support and the
      obstetrical follow-up must be intensive too. An institutional pharmacovigilance
      service should complement the one provided by the industry. Also, further case
      control and cohort studies are essential to better estimate the long-term risks.

PMID- 14567164
TI  - [Failure effects and gender differences in perfectionism].
AB  - Perfectionism is a dimension which has been studied very little as a separate
      entity. It is not even considered as a nosological factor. No classification of
      the medical sciences underlines its importance other than to speak of a
      personality trait, of an aspect, or of a parameter. Nevertheless, perfectionism
      is related to multiple disorders such as depression (18, 20, 36), suicide (8, 16,
      55), nutritional problems (11, 28), anxiety (3), obsessive-compulsive personality
      disorder (53), social phobia (2), as well as insomnia (46). Certain authors
      stress the possible role of perfectionism in the development or the persistence
      of a substantial number of these disorders (7, 22, 38). Given these facts, it is
      all the easier to understand the interest shown by clinicians and researchers in
      the subject. Better detection and evaluation of its impact on behaviour is
      important in putting therapies in place (6, 53). Relationships between
      perfectionism and fear of failure have been approached (21, 51, 54). Correlations
      between perfectionism and high levels of state and trait anxiety have been
      demonstrated (23). The evaluation of perfectionism has been dealt with very
      little. Some questionnaires devote a sub-category to it, such as the Eating
      Disorder Inventory and the Irrational Beliefs Test. However, recently, it has
      been recognized that perfectionism is a multidimensional construct. Two
      Multidimensional Perfectionism Scales have been developed and investigated in
      relative isolation. Frost, Marten, Lahart and Rosenblate defined perfectionism as
      the setting of excessively high standards for performance associated with
      critical self-evaluation. Six dimensions are described: concern over making
      mistakes, high personal standards, parental expectations, parental criticism,
      doubt about quality of performance and organization. Internal consistency and
      validity have been established (25, 26). Hewitt and Flett (30, 31, 33, 35) have
      developed another approach where three dimensions of perfectionism are described:
      SOP (Self Oriented Perfectionism) related to high standards and self criticism,
      SPP (Socially Prescribed Perfectionism) related to the need of approval from
      others and fear of negative evaluation, OOP (Other-Oriented Perfectionism)
      reflecting a tendency to set high expectations for others and to evaluate them in
      a demanding way; this component is related, especially for males, to self-esteem,
      hostility and authoritarianism. Validity and internal consistency have been
      established too (30, 31, 35). The Frost and al's Multidimensional Perfectionism
      Scale and the Hewitt and Flett's scales are closely associated, except concerning
      the OOP. Because this component could provide new information, we have chosen the
      second scale, referring to the French translation and validation of Labrecque
      (45). EMP is the French name of MPS; it is a self-report questionnaire of 45
      questions, in fact three subscales of 15 items rated on a 7-point Likert-type
      scale. MPS was administered to 617 first year students at the university of Liege
      (table II). Differences are considered according to gender and experience of
      failure i.e. the fact of repeating an academic year. We realized a component
      analysis with promax rotation. Among the different possibilities offered by the
      scree-test the choice of a 4 factor solution stresses the original structure: SOP
      (14 items), SPP (12 items), OOP (9 items) and anti OOP (10 items); the last one
      is additional but allows for respecting semantics and saturation of the items.
      The first aim of confirming validity and internal consistency is satisfactory. In
      other respects the multidimensional structure of the concept leads to
      consideration of a positive, adaptive perfectionism and a more negative
      perfectionism, facilitating psychopathology (59, 60, 61). So it seems interesting
      to compare the different components of MPS in order to find an eventual sex
      failure effect. The evaluation of perfectionism is obvious, considering it as a
      personality trait, but it can be used also in taking into account stress and its
      impact, for instance that of academic performance (29, 37, 39, 58). Conferring on
      MPS more pertinence in gender differentiation and failure evaluation is an other
      goal of this research. Through the particular choice of statistical results, sex
      and sex-failure effects can be demonstrated: a MANOVA underlines sex effect
      (lambda de Wilks = 0.96, p = 0.001) and sex-failure effect (lambda de Wilks =
      0.98, p = 0.05). Structure of MPS is different in four groups (FE: women with
      failure, FnE: women without failure, ME: men with failure, MnE: men without
      failure). ANOVA show differences of MPS3, MPS1 and MPS2. Far more promising is
      the use of LISREL method allowing for the construction of a coherent model of
      relationships between some dimensions of MPS and Test-Anxiety, approached here
      with THEE (test d'habilete aux etudes et a leur evaluation) French abbreviated
      version (49) of TASTE (Test for Ability to Study and Evaluation). In fact
      according to the literature of fear of failure, girls score higher on anxiety and
      procrastination but less on self-confidence. The structural model shows different
      pathways, more especially between SPP (socially prescribed perfectionism), T2
      (sense of incompetence) and T1 (anxiety). SOP (self oriented perfectionism) and
      SPP (socially prescribed perfectionism) by girls are very much correlated; it
      seems that they are more subjected to society and its exigencies of studying but
      consequently they are more at risk of anxiety and a sense of incompetence. SOP
      (self oriented perfectionism) by boys functions more indiscriminately of SPP
      (socially prescribed perfectionism) and is negatively correlated with self
      incompetence; boys are more self-confident but they usually procrastinate more
      probably because failure expectancies would be particularly harmful for their
      self-esteem; consequently, failure should be related to something else than their
      own capacity; this may be an explanation of the high rate of male dropouts and
      failure in the first year at the university of Liege; also a factor explaining
      the female domination at the university. In the same way the first choice of
      studies is moving towards shorter and less difficult orientation (46). In case of
      failure the model is very similar according to gender: SOP (self oriented
      perfectionism) and T1 (anxiety) are directly connected; SOP and SPP are in this
      case better correlated by boys but the path between SPP, sense of incompetence
      and anxiety is less significant than in girls. In conclusion, providing some
      modifications according to semantics, the choice of a four factor solution allows
      for confirmation of the original structure of MPS and for internal consistency.
      The different components of MPS vary according to gender: SOP and more OOP
      discriminate men and women; SPP allows for differentiating women with failure. A
      structural model enhances the role of perfectionism in the cognitive and
      behavioural contexts; for instance it clarifies its action on fear of failure and
      success rates according to gender.

PMID- 14567165
TI  - [Caregiver burden in relatives of persons with schizophrenia: an overview of
      measure instruments].
AB  - The high prevalence and chronic evolution of schizophrenia are responsible for a
      major social cost. The adverse consequences of such psychiatric disorders for
      relatives have been studied since the early 1950s, when psychiatric institutions
      began discharging patients into the community. According to Treudley (1946)
      "burden on the family" refers to the consequences for those in close contact with
      a severely disturbed psychiatric patient. Grad and Sainsbury (1963) and Hoenig
      and Hamilton (1966) developed the first burden scales for caregivers of severely
      mentally ill patients, and a number of authors further developed instruments
      trying to distinguish between "objective" and "subjective" burden. Objective
      burden concerns the patient's symptoms, behaviour and socio-demographic
      characteristics, but also the changes in household routine, family or social
      relations, work, leisure time, physical health.... Subjective burden is the
      mental health and subjective distress among family members. While the first
      authors referred to those problems which are deemed to be related to, or caused
      by the patient, Platt et al. (1983) tried to distinguish between the occurrence
      of a problem, its alleged aetiology, and the perceived distress, when developing
      the SBAS questionnaire. These authors also proposed separate evaluations of
      behavioral disturbance and social performance by relatives, and a report of extra
      disease stressors in family life. The SBAS is actually the most complete, but
      also complex instrument for evaluating burden in caregivers. Since 1967
      Pasamanick and others proposed questionnaires for burden evaluation in relatives
      of schizophrenic patients. Relatives may be included in specific
      psychoeducational programs, but few of these programs have been evaluated in
      terms of caregiver burden. The theoretical approach in schizophrenia was not
      different from that one adopted in mentally ill population. Some instruments were
      validated first in a mentally ill group and then adapated for schizophrenic
      population. This paper describes the available data about intruments measuring
      caregiver burden in relatives of schizophrenic patients. Measures are summarized
      according to purpose, content and psychometric properties. Sixteen instruments
      have been collected from the litterature (1955-2001), and 2 instruments developed
      for relatives of mentally ill have also been taken into account. A group of 5
      instruments focuses on the measurement of behavioural disturbance in persons with
      schizophrenia as perceived by their family members. Eleven scales include
      behavioural disturbance in a more complete decription of objective burden.
      Thirteen questionnaires also report the subjective distress in caregivers. One
      instrument has been developed in french language. Few of these instruments have
      been developed from a verbatim and really describe the caregiver's point of view.
      Most of them rely on experts point of view or on previously published studies.
      The content and domains explored by these instruments are variable. The
      psychometric properties are poorly documented for a number of them and no
      information is published about responsiveness. Some validated instruments are the
      Perceived Family Burden Scale (PFBS) the Involvement Evaluation Questionnaire
      (IEQ) and the Experience of Caregiving Inventory (ECI). In past studies,
      researchers more or less agreed about the dimensions that comprise the family
      burden. There was less agreement with regard to the definition of objective and
      subjective burden, and quite no agreement about the theoretical approach to the
      concept of burden. The evaluation of behavioural disturbance should now be
      excluded from the objective burden dimension. It is a specific domain, both
      objective and subjective, which can be described as a stressor in the stress
      appraisal-coping model. A good approach of this domain can be found in the PFBS.
      It comprises 24 items and the principal components analysis produces 2 factors
      ("active" and "passive"), explaining 35% of the variance, with good consitency
      and acceptable test-retest reliability. The evaluation is both objective
      (presence or absence) and subjective (induced distress). The Behavior Disturbance
      Scale (BDS) may also be taken into account, although it is less validated. This
      scale derives from the SBAS, modified as a self-questionnaire, with both
      objective and subjective evaluations of all items. The concept of burden was
      recently modified in a new theoretical approach by Schene, when developing the
      IEQ. According to this author, the burden scale is supposed to exclude stressors
      (patient's behaviors), as well as outcome variables (distress or psychological
      impairment in caregiver). The "caregiving consequences" section comprises 36
      items, which focus on the subjective aspects of the caregiver's experience.
      Principal component factor analysis generates 4 factors which explain 45% of the
      variance: tension, supervision, worrying, urging. The overall caregiving score
      substantially explains the connection between patient, caregiver, relationship
      variables and the caregiver's distress. This scale is a valid and simple
      instrument for caregiving eveluation The ECI also introduces a new approach of
      caregiving and rejects the notion of burden. The 66 item version is composed of
      10 factors (8 "negative" and 2 "positive") with good internal consistency. The
      introduction of two positive factors (rewarding personal experiences, good
      aspects of the relationship with the patient) might be the basis of a useful
      outcome measure for intervention aimed at promoting caregiver well-being.
      Nevertheless, the authors fail to develop an overall score that includes these
      factors, and focus on the negative dimensions as predictors of morbidity and well
      being. None of the variables included in the regression model explain a
      significant percent of the variance of the ECI positive score. None of these
      instruments was employed for evaluating programs or treatments, even
      psychoeducational programs for caregivers. This may be partly due to the lack of
      data about sensitivity to change. No instrument is now available for evaluating
      therapeutics from the caregiver's point of view. Developing such an instrument is
      necessary, in view of the increasing role of families in care for schizophrenic
      patients. These data and the review of the literature leeds us to propose the
      development of a self-administered questionnaire for evaluating subjective health
      related quality of life in caregivers of schizophrenic patients. The instrument
      should be developed from the caregiver's point of view and be derived from
      qualitative interviews with relatives of patients suffering from schizophrenia.
      It's responsiveness should be documented before inclusion in clinical trials or
      evaluation of psychoeducational programs. We are now working with the National
      Union of Friends and Families of Patients to validate an instrument in french
      language.

PMID- 14567166
TI  - [Predictive factors in social adaptation disorders in anorexic and bulimic
      patients].
AB  - A lifetime diagnosis of at least one anxiety disorder has been found in 13% to
      75% of women with BN (Herzog, Keller, Sacks, Yeh, & Lavori, 1992; Schwalberg,
      Barlow, Alger, & Howard, 1992), and in 20% to 55% of women with AN, (Herzog et
      al., 1992, Laessle et al., 1989). Wittchen et al., 1998) have observed that the
      frequency and degree of disabilities and impairments associated with mental
      disorders in adolescence are strongly related to comorbidity (notably with
      anxiety disorders). However, as noted by Wonderlich et al., 1997, no study has
      compared ED individuals with and without comorbid anxiety disorders in terms of
      clinical or general functioning. The current study was designed to determine
      whether social avoidance symptoms and/or comorbid lifetime anxiety disorders were
      predictive factors of social disability in subjects with ED (AN or BN). We
      focused on two main dimensions of social adaptation, regarding social and
      professional life. 63 subjects with anorexia nervosa or bulimia nervosa were
      assessed for lifetime diagnoses of anxiety disorders, childhood history of
      separation anxiety disorder, social avoidance symptoms, and social disability.
      Sociodemographic characteristics, lifetime diagnoses of ED and anxiety disorders,
      and ages at onset of each disorder present, were assessed using the French
      version of the Composite International Diagnostic Interview (CIDI) (Robins et
      al., 1988; WHO, 1990). In addition, childhood history of separation anxiety
      disorder, not included in the CIDI, was assessed using the appropriate section of
      the Schedule for Schizophrenia and Affective Disorders Lifetime Version--Modified
      for the study of Anxiety Disorders (SADS-LA-R) (Endicott, Spitzer, 1978;
      Mannuzza, Fyer, Klein, 1985). Social anxiety symptoms were measured on Liebowitz
      Social Phobia Scale (Liebowitz, 1987). Social adjustment was assessed using a
      semi-structured interview, the Groningen Social Disabilities Schedule-Second
      version (GSDS-II) (Wiersma, De Jong, Ormel, & Kraaij Kamp, 1990). For each of the
      two outcome variables regarding disability, the Social role and the Occupational
      role, all subsets logistic regression analysis was performed in accordance to
      Hosmer and Lemeshow's guidelines (Hosmer and Lemeshow, 1989). Our total sample of
      63 subjects included 29 subjects with AN restricting type (27 women, 2 men; 7%
      with a past history of BN) and 34 subjects with BN purging type (all women; 53%
      with history of a previous episode of AN). On the Groningen Social Disabilities
      Schedule, 86% of the anorexics and 65% of the bulimics had disability regarding
      the "social role", and 86% and 61%, respectively, disability regarding the
      "occupational role". Using all subsets logistic regression analyses, predictive
      factors of disability were: 1) for the social role, social avoidance symptom
      score (p < 0.002) and diagnosis of separation anxiety disorder (p < 0.01); 2) for
      the occupational role, number of lifetime anxiety disorders (p < 0.01) and
      diagnosis of separation anxiety disorder (p < 0.06). The present study clearly
      demonstrates that social avoidance and anxiety disorders are common and important
      features in the clinical presentation of subjects with AN or BN, and that they
      can have a negative impact on both their social and their occupational
      adaptation. Chronicity is a major risk in the ED, in terms of medical and
      sometimes lethal complications, but also because of the social consequences of
      these disorders. It is therefore important, in subjects with ED, to identify
      comorbid conditions linked to social disability, in order to improve global
      outcome. Recognizing and treating comorbid anxiety disorders in subjects with AN
      or BN could give better results than treating only the ED, in terms of social as
      well as global psychopathological outcome.

PMID- 14567167
TI  - [Preliminary validation of the French translation of anxiety sensibility index
      revised (ASI-R)].
AB  - Anxiety sensitivity represents a stimulus-outcome expectancy that reflects
      individual differences in the propensity to experience fear in response to one's
      arousal-related bodily sensations. It refers to the fear of anxiety-related
      symptoms that are based on beliefs that such sensations have negative somatic,
      social or psychological consequences. Anxiety sensitivity occupies an important
      place in theory and research on panic and related interoceptive fear disorders.
      Findings from this body of research indicate that this construct may act as a
      specific vulnerability variable in the development of panic attacks and anxiety
      symptoms. However, anxiety sensitivity theory also has been applied to
      understanding mood disorders and chronic pain disorders. Thus, as a psychological
      construct, anxiety sensitivity holds specific relevance to understanding panic
      disorders and general relevance for expanding knowledge about negative emotional
      functioning in other pathologies. All the research on anxiety sensitivity has
      been completed with the 16-item Anxiety Sensitivity Index (ASI). The review of
      the literature using this instrument suggested that anxiety sensitivity has three
      lower-order factors that all load on a single higher-order factor. The lower
      order factors represent Physical-Concerns, Mental Incapacitation Concerns, and
      Social Concerns, and the higher-order factor represents the global anxiety
      sensitivity construct (21). Taylor and Cox (22) suggested that this questionnaire
      was not designed on an a priori basis to measure the identified lower-order
      factors. The low number of items for the Social and Mental Incapacitation
      dimensions of the 16-item ASI often leads to relatively lower levels of
      reliability compared to the third dimension. To address this issue, Taylor and
      Cox (22) developed an expanded measure of the anxiety sensitivity construct. The
      36-item Revised Anxiety Sensitivity Index (ASI-R) maintains the same format as
      the 16-item ASI, but expands the number of content domains assessed. The ASI-R
      was designed to assess 6 lower-order domains identified in previous factor
      analytic research using the 16-item ASI (21), including fear of cardiovascular
      symptoms, fear of respiratory symptoms, fear of gastrointestinal symptoms, fear
      of publicity observable reactions, fear of dissociative and neurological
      symptoms, and fear of cognitive dyscontrol. The principal components factor
      analysis using the ASI-R among psychiatric outpatients indicated that there were
      4 lower-order factors tapping the constructs of (1) fear of respiratory symptoms,
      (2) fear of publicly observable anxiety reactions, (3) fear of cardiovascular
      symptoms, and (4) fear of cognitive dyscontrol (22). A recent study (27) provided
      an initial psychometric evaluation of the ASI-R in a large, diverse sample of
      people (n = 2,786) from 6 different countries: Canada, United States, Mexico,
      Spain, The Netherlands and France. The data suggested that the two-factor
      solution is most replicable than other solutions (2 to 6 factors). The underlying
      structure of the anxiety sensitivity construct was generally similar across
      countries, tapping fear about the negative consequences of anxiety-related
      physical and social-cognitive sensations. Lower-order factors were moderately to
      strongly correlated with one another and showed good internal consistency. This
      manuscript presents the French translation of the ASI-R and a preliminary
      validation study. This research was realized conjointly with the transcultural
      study previously mentioned (27). Seven hundred and one French university students
      (non-clinical participants) completed the questionnaire at the beginning of a
      class. Subjects were undergraduate students from 2 universities (psychology and
      classics). Table I provides age, sex and marital status. There were no
      differences between the two groups on sex. The two groups were not comparable on
      age and marital status. The psychology group was older than the other was. The
      psychology students were also more married. The total group (n = 701) comprises
      79 men and 622 women, with a mean age of 21.29 (4.85). Table II provides the
      normative means and standard deviations for both groups of students. There was no
      difference between the two groups on the total of the questionnaire (no
      significant interaction between group and age). In regard to the physical
      concerns subscale and the social-cognitive concerns subscale, there was also no
      significant interaction between group and age. Assessment of the internal
      consistency of the ASI-R yielded an overall Cronbach alpha of 0.91 for the entire
      questionnaire, with an alpha of 0.88 for the fear of anxiety-related physical
      sensations subscale and 0.83 for the fear of anxiety-related social-cognitive
      sensations subscale. A series of ANOVAs between male and female groups revealed
      significant gender differences. As shown in table IV, women had significantly
      higher total score than did men. They also had significantly higher physical
      factor and social-cognitive factor scores than did men. This finding is
      consistent with research that indicates that women generally report more intense
      fears and men less intense fears, and that they differ in levels of overall
      anxiety sensitivity specifically (29). This preliminary report was the first
      attempt to examine the construct of anxiety sensitivity using the ASI-R in a
      French university students. It can serve as a reference point for future
      research.

PMID- 14567168
TI  - [Pilot study comparing in blind the therapeutic effect of two doses of
      agomelatine, melatonin- agonist and selective 5HT2c receptors antagonist, in the
      treatment of major depressive disorders].
AB  - RATIONALE AND METHOD: Two doses of agomelatine (S-20098), a novel potential
      antidepressant drug with a new pharmacological profile (melatonin agonist and
      selective 5HT2C antagonist), were compared in a double-blind, randomised, pilot
      study in order to estimate the antidepressant activity shown in preclinical data.
      Inpatients suffering from major depressive disorder (DSM III-R criteria) and
      presenting a minimal score of 25 for MADRS were selected at D-7. After one week
      of run-in placebo treatment, included patients received one evening dose of
      agomelatine (either 5 or 100 mg) for 4 to 8 weeks. Hospitalization was required
      at least for the first 3 weeks. Patients presenting a satisfying response to
      treatment (MADRS total score < 15 or decrease > or = 40% from inclusion score)
      could be treated as outpatients. A follow up of 2 weeks was performed after
      stopping the treatment. The total duration of the treatment period could vary,
      according to investigator's decision, between 7 and 11 weeks. Evaluation criteria
      included MADRS, HAMD-17, HAM-A, CGI and AMDP 5 at D0, D7, D14 and D28, and, when
      applicable, at D35, D42, D49 and D56. Safety evaluations included recording of
      adverse events, ECG monitoring and biology. RESULTS: Thirty inpatients were
      selected and 28 included (14 per group). There was no major difference between
      groups at inclusion, neither for demographic nor evaluation criteria. One patient
      of each group was excluded of the ITT analysis; 19 patients completed the
      mandatory period up to D28: 10 in the 5 mg group and 9 in the 100 mg group; 10
      patients (5 in each group) carried on the study during the optional period, up to
      D56 for 7 out of them (4 in the 5 mg group, 3 in the 100 mg group). Efficacy
      criteria showed a significant improvement in both groups, with highly significant
      within group evolutions (p < 0.001 whatever the criteria) and without significant
      difference between groups. However, better results were observed in the 5 mg
      group compared to the 100 mg group. Total MADRS scores then decreased from 30.7
      +/- 3.5 to 14.8 +/- 6.4 in the 5 mg group vs a decrease from 31.6 +/- 4.7 to 18.6
      +/- 14.8 in the 100 mg group. Furthermore, significant improvement between D14
      and D28 visits were only seen in the 5 mg group. Analysis of somatic complaints
      (AMDP 5) showed with both treatments a strong decrease of symptoms during the
      study, especially for items related to sleep disorders (difficulties in falling
      asleep, interrupted sleep, shortened sleep, early wakening and drowsiness).
      Acceptability was good for both doses of agomelatine. However, there were
      slightly more emergent adverse events and severe treatment-related adverse events
      in the 100 mg group. No modifications of cardio-vascular parameters nor
      biological abnormalities were observed in both groups. CONCLUSION: Preliminary
      clinical data with agomelatine confirm the potential antidepressant effect in
      accordance with positive preclinical results. There was no significant difference
      between 5 and 100 mg, both for efficacy and for safety. However, the data suggest
      that 5 mg could be a dose at least as effective and slightly better tolerated
      than 100 mg. Further double-blind controlled studies versus active comparators
      and placebo are required in order to confirm these results.

PMID- 14567169
TI  - [Frontal dementia or dementia praecox? A case report of a psychotic disorder with
      a severe decline].
AB  - INTRODUCTION: Many authors have described these last years the difficulty to
      establish a differential diagnosis between schizophrenia and frontotemporal
      dementia. However treatment and prognosis of these two separate diseases are not
      the same. Schizophrenia is a chronic syndrome with an early onset during teenage
      or young adulthood period and the major features consist of delirious ideas,
      hallucinations and psychic dissociation. However a large variety of different
      symptoms describes the disease and creates a heterogeneous entity. The diagnosis,
      exclusively defined by clinical signs, is then difficult and has led to the
      research of specific symptoms. These involve multiple psychological processes,
      such as perception (hallucinations), reality testing (delusions), thought
      processes (loose associations), feeling (flatness, inappropriate affect),
      behaviour (catatonia, disorganization), attention, concentration, motivation
      (avolition), and judgement. The characteristic symptoms of schizophrenia have
      often been conceptualised as falling into three broad categories including
      positive (hallucination, delision), negative (affective flattening, alogia,
      avolition) and disorganised (poor attention, disorganised speech and behaviour)
      symptoms. No single symptom is pathogonomonic of schizophrenia. These
      psychological and behavioural characteristics are associated with a variety of
      impairments in occupational or social functioning. Cognition impairments are also
      associated with schizophrenia. Since the original clinical description by
      Kraepelin and Bleuler, abnormalities in attentional, associative and volitional
      cognitive processes have been considered central features of schizophrenia. Long
      term memory deficits, attentional and executive dysfunctions are described in the
      neurocognitive profile of schizophrenic patients, with a large degree of
      severity. The pathophysiology of schizophrenia is not well known but may be
      better understood by neuronal dysfunctions rather than by a specific anatomical
      abnormality. Frontotemporal lobar degeneration (FTLD) is one of the most common
      causes of cortical dementia. FTLD is associated with an anatomical atrophy that
      can be generalised, with a frontotemporal or focal lobar predominance.
      Histologically there is severe neuronal loss, gliosis and a state of spongiosis.
      In a minority of case Pick cells and Pick bodies are also found. The usual
      clinical features of FTLD are divided in three prototypic syndromes:
      frontotemporal dementia (FTD), progressive non-fluent aphasia (PA) and semantic
      dementia (SD). FTD is the most common clinical manifestation of FTLD. FTD is
      first characterised by profound alteration in personality and social conduct,
      characterised by inertia and loss of volition or social disinhibition and
      distractibility. There is emotional blunting and loss of insight. Speech output
      is typically economical, leading ultimately to mutism, although a press of speech
      may be present in some overactive, disinhibited patients. Memory is relatively
      preserved in the early stage of the disease. Cognitive deficits occur in the
      domains of attention, planning and problems solving, whereas primary tools of
      language, perception and spatial functions are well preserved. PA is an initial
      disorder of expressive language, characterised by effortful speech production,
      phonologic and grammatical errors. Difficulties in reading and writing also occur
      but understanding of word meaning is relatively well preserved. In SD a severe
      naming and word comprehension impairment occur on the beginning in the context of
      fluent, effortless, and grammatical speech output. There is also an inability to
      recognise the meaning of visual percepts. The clinical syndromes of FTLD are
      associated with the brain topography of the degeneration. So considerable
      clinical overlap can exist between schizophrenia and FTLD and the object of the
      following case report is to remind the difficulty to make a differential
      diagnosis between these two pathologies. CASE REPORT: A 34 year old non-married
      man is admitted in mental health district of a general hospital for behavioural
      disturbances that include repeated aggressions towards his family. At initial
      interview visual and auditives hallucinations are described. The patient doesn't
      care about these abnormalities and a poverty of speech is observed. The affects,
      globally blunted, show some degree of sadness however. The patient's birth and
      early development were unremarkable. At the age of 26, the patient dismissed from
      his job because of poor performance and absenteeism. He spent a lot of time
      watching TV, showed poverty of speech and become sometimes angry and violent
      without an explanation. He was hospitalised for several months and a
      schizophrenia including predominant negative features, hallucinations and
      delusion was diagnosed. He was treated with bromperidol, could go back to home
      and was followed by a general practitioner for 8 years. The patient had a
      stereotyped way of life during these years with a poor communication and little
      activity. During the months preceding the current hospitalisation, these
      characteristics and avolition emphasised, urinary incontinence appeared. The
      patient receives risperidone 8 mg/day associated with citalopram 40 mg/day during
      several months of hospitalisation. No significant evolution is observed regarding
      apathic and stereotyped way of live. The capacity of communication remains very
      poor. Neurocognitive assessments reveal multiple and severe dysfunctions. Memory,
      executive and attentional tasks are extremely disturbed. Physical and
      neurological examinations reveal an isolated bilateral Babinski sign. Cerebral
      scanner and magnetic resonance show bifrontal atrophy and PET scan is normal.
      There are no significant abnormalities found on blood and urine samples and on
      lumbar puncture. The patient is sent to a chronic neuropsychiatric hospital and
      the treatment is stopped. One year later, a comparative evaluation is realised.
      The general clinical state shows no evolution. Neurocognitive assessments are
      repeated and severe dysfunctions are observed with more perseverations.
      DISCUSSION: A diagnosis of FTLD for this patient can be discussed regarding
      clinical features, neurocognitive testings and neuroradiological findings.
      Schizophrenia is a major differential diagnosis. Psychotic symptoms like
      hallucinations and age of onset are essential observations for the diagnosis of
      schizophrenia but can not exclude FTLD. Memory, intellectual functions, executive
      and attentional abilities may all be disturbed in schizophrenia and FTLD.
      Cerebral abnormalities well established in schizophrenia are lateral ventricles
      enlargements. Frontal lobar atrophy is a major argument for FTLD and is only a
      sporadic finding in schizophrenic populations. Schizophrenia and FTLD could be
      comorbid diseases by several ways. CONCLUSION: A differential diagnosis between
      schizophrenia and FTLD is difficult to establish. Schizophrenia is a
      heterogeneous disease with a large variety of cognitive dysfunctions.
      Neurocognitive tools may improve our knowledge of schizophrenia.

PMID- 14567170
TI  - [The pattern of injury in polytraumatized patients].

PMID- 14567171
TI  - [Changes in the injury pattern of polytraumatized patients over the last 30
      years].
AB  - This study aims at describing the changes in injury patterns in traffic accidents
      in Germany that have taken place over a 30 year period. The basis for the
      analysis is the in-depth investigations by the scientific research team at the
      Trauma Department of the Hanover Medical School. Real accidents were investigated
      based on an on site random selection process. The study includes 1,235 accidents
      from 1973 to 1978 and 5,608 accidents from the years 1994 to 1999. A reduction in
      number of fatalities, as well as a change in the injury pattern and the time of
      death in fatalities was observed. In the earlier years, 54.2% of the fatalities
      occurred during hospital treatment, whereas in the currant years 78.8% of the
      fatalities occurred directly at the accident scene and were mainly caused by much
      higher impact levels. In the earlier group, the polytraumatised patients suffered
      injuries of AIS 3+ to nearly all body regions (head 69.6%, thorax 69.2%, abdomen
      51.9%, pelvis 33.1% and lower extremities 51.9%), whereas today only the head and
      chest are dominant injury locations for life-threatening trauma. Analysis of the
      collision configuration showed that nowadays the impact of cars against
      structures with a low profile such as poles and trees is responsible for the
      majority of severe, life-threatening injuries, whereas other injury patterns are
      of minor importance. For pedestrians and cyclists, the impact of the body on the
      windscreen of the car is the major reason for severe injuries. We conclude that
      the currently used safety methods have led to a change in the injury pattern of
      polytraumatised victims. Injuries with much higher energy levels can nowadays be
      survived, but when the safety limits are exceeded immediate death at the scene is
      more common.

PMID- 14567172
TI  - [Quality of life after surgical treatment of osteitis].
AB  - Although many studies have measured the functional outcome after surgical
      treatment of osteomyelitis, there have been few published attempts to evaluate
      the long-term quality of life. We therefore undertook this study to assess the
      quality of life in a large patient population after operative treatment for this
      condition. All patients who underwent operative treatment for osteomyelitis from
      1993 until 1997 at our institution were included in the study. The patients were
      assessed with a questionnaire which contained the SF-36 (German version) and
      questions about the activity and history of the illness. The result was compared
      to the data set from a standard population. Of the 502 patients, 345 (69%)
      returned questionnaires for evaluation. The infection was inactive in 301 (88%).
      Compared to a standard population, the investigated patients showed a significant
      reduction in their overall psychological well being and physical functional
      capacities. Surgical treatment was able to inactivate the infection in 88% of the
      patients. Because of persistent deficits, the psychological well being and
      physical functional capacities are reduced compared to a standard population.

PMID- 14567173
TI  - [10-year results of bone marrow stimulating therapy in the treatment of
      osteochondritis dissecans of the talus].
AB  - The optimal operative therapy for the treatment of osteochondritis dissecans tali
      is still controversial. Beside bone marrow-stimulating techniques like abrasion
      arthroplasty, drilling and microfracturing, new techniques like autologous
      osteochondral transplantation and autologous chondrocyte transplantation are
      increasingly used. This study reviewed the clinical, radiological and subjective
      long-term outcome of bone marrow-stimulating therapy for 45 ankles with an
      osteochondritis dissecans tali stage 3 or 4 according to the classification by
      Berndt and Harty. All ankles were treated by the removal of the dissecate and
      abrasion of the subchondral bone. In 67%, an additional antegrade drilling of the
      defect was performed. The average maximum size of the lesion was 1.1 cm. At
      follow-up examination, 10.4 years (7.1-13.5 years) postoperatively, the average
      AOFAS-score was 91 points (66-100 points). Using the score of Mazur, the outcome
      of 28 ankles (62%) was rated excellent, 12 ankles (27%) were rated good and five
      ankles (11%) fair or poor. Progressive osteoarthritic changes, according to the
      classification of van Dijk, were seen in seven ankles (16%). Reoperations were
      necessary in eight cases (18%). Obesity, age older than 40 years and preoperative
      osteoarthritic changes had a significant negative impact on the clinical outcome.
      Bone marrow stimulating therapy is an inexpensive, low invasive therapy and a
      good therapeutic option at least for small Berndt/Harty stage 3 and 4 ODT
      lesions. Autologous chondrocyte transplantation and osteochondral autografts
      yield encouraging 2- and 4-year results, but still have to prove their
      superiority in long-term follow-up studies.

PMID- 14567174
TI  - [Femoral neck fractures in the elderly -- bipolar hemiarthroplasty in total hip
      replacement].
AB  - INTRODUCTION: In this study surgical risk and functional outcome of bipolar
      hemiarthroplasty and total hip replacement in elderly patients with femoral neck
      fractures were compared. METHODS: In a prospective study 54 patients with femoral
      neck fractures (median age: 80.5 years) were treated by implanting a total hip
      replacement (group I). Group II comprised 52 patients with 55 femoral neck
      fractures (median age: 81 years) who underwent bipolar hemiarthroplsty. Pre- and
      postoperative mobility and social history, perioperative parameters such as
      duration of surgery, blood loss, and number of transfused blood units as well as
      postoperative complications and mortality were compared. Function was ascertained
      by a scoring system. RESULTS: Duration of surgery, blood loss, and numbers of
      transfused blood units were significantly lower in group II, and mortality rate
      was lower. Postoperative mobility and medium-term functional score were
      comparable, whereas in the longer-term follow-up after 8 years group I had a
      significantly better functional score. CONCLUSION: In elderly patients with
      femoral neck fracture and high comorbidity, we recommend the implantation of
      hemiarthroplasty and in healthy, active patients with longer life expectancy the
      total hip replacement.

PMID- 14567175
TI  - [External or internal fixation for arthrodesis of the ankle -- a comparative
      study of perioperative and long-term results].
AB  - SUBJECT: This study evaluates the results of external and internal fixation
      techniques for arthrodesis of the ankle. METHODS: Perioperative and subjective,
      clinical, and radiological long-term results (average follow-up: 9 years) in 55
      patients following arthrodesis of the ankle due to posttraumatic arthritis were
      compared in two groups with different fixation techniques--compression
      arthrodesis with external fixator (AO) or internal screw fixation. RESULTS:
      Patients with external fixation revealed a significantly higher deep infection
      rate, which was treated conservatively, while the rates of nounion, revision
      surgery due to infection, and total revision surgery did not show any difference
      in the two groups. CONCLUSION: Both surgical techniques applied mostly guarantee
      a safe and stabile fixation in arthrodesis of the ankle and provide convincing
      long-term results without showing a difference in comparing the outcome.

PMID- 14567176
TI  - [Influence of processing and sterilization on the mechanical properties of pins
      made from bovine cortical bone].
AB  - In a biomechanical study pins made of xenogenous cortical bone were tested in
      vitro. Forty pins of 3 mm diameter and 60 mm length were made of eight different
      cattle tibiae and allocated to five different treatment groups. Freeze-dried pins
      served as control group. Pins of the second group were preserved in concentrated
      sodium chloride solution and defatted with acetone (Tuto-plast processing). Pins
      of groups three to five were treated with sodium chloride and acetone and
      afterwards sterilized by different means (ethylene oxide, autoclavation, or gamma
      radiation). All pins were subjected to a three-point-bending test and a shear
      test. We found that bending strength and shearing strength were most increased
      after sodium chloride and acetone treatment, whereas after sterilization with
      ethylene oxide or autoclaving, the stability of the pins was similar to the
      control group. The stability was considerably diminished after gamma radiation.
      Taking into account possible toxic side effects of ethylene oxide, we conclude
      that Tutoplast processing followed by autoclavation presents a reliable
      preparation method for the clinical use of implants made of bovine cortical bone.

PMID- 14567177
TI  - [Results of the surgical treatment of arthro-fibrosis of the knee].
AB  - This retrospective study reports the evaluation of the surgical treatment of
      arthrofibrosis of the knee joint. Patients (n = 53) developed arthrofibrosis due
      to different index operations and various causes. Based on severe preoperative
      disability, patients of our series can be considered as difficult to treat. Our
      management concept suggests a step by step, pathology-oriented treatment: if
      necessary, arthroscopic arthrolysis and gentle manipulation is supported by
      posterior capsulotomy. To evaluate the results, we assessed the range of motion
      of the knee joint, the relative gain in range of motion, extension- and flexion
      deficit, as well as the Tegner, Lysholm and Flandry score. As a result of
      arthrolytic surgery, all 53 patients showed statistically significant (P < 0.01)
      improvement of the above parameters. The mean gain in the range of motion was
      73%. To emphasize the importance of the correct timing of arthrolysis, patients
      were divided into early and late arthrolysis groups. patients with an early
      arthrolysis obtained a significantly (P < 0.01) greater improvement in the
      absolute range of motion than those with a later treatment. By the additional
      procedure of a posterior capsulotomy, the average extension deficit (absolute)
      was significantly (P < 0.01) more reduced than for patients without this
      treatment. Our data support an early therapeutic intervention for patients with a
      large restriction in the range of motion. Patients with an extension deficit
      after arthroscopic arthrolysis and gentle manipulation will improve with the
      additional procedure of posterior capsulotomy.

PMID- 14567178
TI  - [Radiation dosage in orthopedics -- a comparison of computer-assisted
      procedures].
AB  - Since the 1990s, computer-assisted methods have been well-established in the
      field of orthopedics and traumatology. In addition to the proven improvement in
      the field of surgical precisioncompared with conventional techniques, the
      decrease in the amount of emitted ionizing radiation inside of the operating room
      was cited to constitute an additional major advantage of computer-based
      navigation. The goal of this study was to quantify X-ray dose values exposed
      during both conventional methods and computer-assisted procedures, the latter
      being performed using a C-arm device SIREMOBIL Iso-C3D (Siemens Medical
      Solutions). The clinical measurements were supplemented by laboratory experiments
      using a pinpoint ionization chamber placed inside a standard lucite phantom. The
      clinical part of the study investigated the application of new, i.e. computer
      assisted, techniques in comparison with conventional procedures on in total 42
      patients experiencing surgery either on their lower extremities (n = 14) or on
      the spine (n = 28). The techniques applied were: (1) conventional surgical
      procedure, (2) CT-based navigation, (3) C-arm navigation, and (4) Iso-C3D
      navigation. The main focus of the clinical evaluation was the determination of
      radiation dose values by means of thermoluminescence dose meters, accompanied by
      the registration of the operation times of the X-ray tube during a surgical
      intervention. The conclusions from the clinical studies are in agreement with the
      results from the laboratory measurements. Computer-assisted techniques led to a
      significant reduction in X-ray dose exposure and drastically shortened
      irradiation times. The most pronounced decrease in the emission of ionizing
      radiation was achieved in case of the Iso-C3D-navigation, which has only recently
      been introduced into clinical practice, i.e. during runtime of this study.

PMID- 14567179
TI  - [Humeral head fractures].
AB  - Humeral head fractures generally may be treated in a non-operative concept with
      early physiotherapy when fragment dislocation is minor. Dislocated 2-part
      fractures (head and shaft fragment) may be treated with closed reduction. If the
      fracture persists unstable, K-wire, cerclage, intramedullary nailing or plate
      osteosynthesis are the eligible methods. Particularly isolated K-wire
      osteosynthesis is associated with a high risk of implant or fragment dislocation.
      Dislocated 3- or 4-part fractures need additional reduction and fixation of the
      tubercles. In osteoporotic fractures, intraosseous fixation may lead to
      complications. Especially cerclage and/or isolated screws (eventually additional
      K-wires) osteosynthesis allows good reduction for functional treatment in the
      older patient. Sufficient results in long-term outcome are achieved by minimal
      invasive techniques even in partial avascular head necrosis. In 4-part fractures
      prosthetic replacement should be considered. Especially when old patients have
      severe destruction or luxation of the humeral calotte prosthetic treatment may be
      indicated. Early functional physiotherapy is important after all types of
      osteosynthesis or prosthesis.

PMID- 14567180
TI  - [Aortic valve insufficiency due to rupture of the cusp in a patient with multiple
      trauma].
AB  - Lesions of the heart valve caused by blunt chest trauma is rare, but when it does
      occur it can significantly injure the patient. On the basis of autopsy studies,
      research shows that heart valves are injured in less than 5% of patients who have
      died due to impact thoracic trauma. Among the heart valves, the aortic valve is
      the most often lacerated, which has been proved by relevant autopsy and clinical
      studies. Aortic valve lesions can be the only injury, but it is possible that
      additional heart or large vessel injuries are also present (myocardial contusion,
      rupture of the atrial septum, aortic rupture, rupture of the left common carotid
      artery). The force that causes such an injury is often great and often causes
      injuries to other organs and organ systems. In a multiple trauma patient, it is
      very important to specifically look for heart-related injuries because it is
      possible that they may be overlooked or missed by the surgeon, because of other
      obvious injuries. We describe the case of a 41-year-old man with multiple trauma
      who was diagnosed with aortic valve insufficiency due to rupture of the left
      coronary cusp 6 weeks after a road accident. Valvuloplasty was performed. Seven
      years later the patient is free of symptoms and is in good physical condition.
      Echocardiography showed normal dimensions of the heart chambers, a normal
      thickness of the heart walls, and normal systolic and diastolic function of the
      left ventricle. Heart valves are morphologically normal, and only an unimportant
      aortic insufficiency was noticed by echocardiography.

PMID- 14567181
TI  - [Subperiosteal pisiform excision in misaligned fractures of the triquetrum].
AB  - Isolated fractures of the os triquetrum are a very rare condition, since they are
      usually combined with other fractures of the carpus. An undetected isolated
      fracture of the os triquetrum in a 28-year-old pieceworker revealed an osseous
      consolidation with a misalignment of the joint surface on presentation 6 months
      after his primary injury. During the whole time he was unable to work due to the
      severely painful restricted range of movement of his wrist. There are no general
      guidelines for treatment. Instead of correction of the anatomy of the os
      triquetrum, we decided to perform a subperiosteal pisiform excision according to
      Palmieri. As early as 6 weeks later, the patient was able to go back to work and
      demonstrated a pain-free full range of movement of his wrist. We encourage this
      procedure not only for degenerated joint disease but also for posttraumatic
      lesions in the early onset of painful blocking of the joint between the os
      triquetrum and os pisiforme.

PMID- 14567183
TI  - Skin lipids.

PMID- 14567182
TI  - [Bleeding into retroperitoneal cavernous lymphangioma following blunt abdominal
      trauma].
AB  - The case of a 12-year-old boy with hemorrhage into a previously unknown
      retroperitoneal lesion following blunt abdominal trauma is reported. Diagnostic
      work-up of a post-traumatic surgical acute abdomen revealed a giant multicystic
      tumor in the retroperitoneum, which could be completely removed. Histological
      examination confirmed the suspected diagnosis of congenital lymphangioma.
      Attention should be drawn to the possible coincidence of trauma and a preexisting
      asymptomatic lesion. Knowledge of the characteristic ultrasonographic and
      computer tomographic features is essential in order to make a correct diagnosis.

PMID- 14567184
TI  - [Metabolic and secretory activities of adipocytes].
AB  - White fatty tissue represents 10 to 25% of the total body weight in a normal
      person. It is the principal site of storage and release of lipids: the stockpile
      of organism's energy. Adipocytes play an essential role in the lipid metabolism
      and participate in endocrine and in autoparacrine regulations. Numerous molecules
      synthesized and released by adipocytes have been described but their precise
      roles have to be studied in vivo before their potential application in treatment
      of obesity or type II diabetes can be proposed.

PMID- 14567185
TI  - [Metabolism of bioactive lipids].
AB  - In addition to their well-known roles as structural elements (amphiphilic lipids
      of the cell membranes) and as energetic reserve (essentially triglycerides), the
      lipids function as "second messengers" is increasingly recognised. Indeed, they
      are also endogenous mediators with specific biological activities, synthesized
      "on request", often in response to a primary cellular signal. Most of the bio
      active lipids originate from cleavage of the membrane structures under the action
      of phospholipases A2, C, D and of sphigomyelinases. Several products of lipolysis
      are involved in cell activation, signalling, apoptosis or proliferation. One of
      the major cascades of bio-active lipid production involves the release of
      arachidonic acid followed by the formation of prostanoids, e.g.: prostaglandins,
      thromboxanes, and of leukotrienes and related products. These molecules play
      major roles in such biological processes as inflammation or thrombosis.
      Arachidonic acid is also the substrate for cytochrome P450-dependent mono
      oxygenases, producing molecules regulating ion fluxes in cell membranes. Action
      of sphingomyelinases leads to the release of ceramides, associated with
      apoptosis. Further hydrolysis of ceramides produces fatty acids and sphingosine;
      the latter being able, in its phosphorylated form, to induce cell proliferation
      and re-equilibrate the balance between cell death and cell renewal.

PMID- 14567186
TI  - [The adipocyte in the history of slimming agents].
AB  - Nowadays, in industrialised societies, it is fashionable for women to be slim.
      However, throughout history, this has not always been the case, especially as
      "cellulite" (cellulitis) was full of typically feminine symbols. The ideal
      feminine silhouette has changed with the rhythm of cultures. Cellulitis is an
      inappropriate term used by women to describe curves which they judge to be too
      plump and not very aesthetic, mostly around the thighs and hips. This
      lipodystrophy of the adipose tissue represents approximately 25% of a woman's
      body weight. It is clinically characterised by an "orange peel" skin surface,
      which is a result of the excessive development of the volume of the adipocytes
      organised in lobules within the walls of the unstretchable conjunctive tissue.
      This phenomenon is associated with an insufficiency of the venous tonus and an
      increase in the capillary permeability, which both contribute to an increase in
      the infiltration of water in the tissue. In reality, the understanding of
      cellulite has truly progressed with research based on adipocyte functions. An
      adipocyte is a metabolically active cell which plays a central role in the
      control of the energetic balance of the organism. In order to assume this role,
      it possesses all the enzymatic equipment necessary for synthesis (lipogenesis)
      and for triglyceride storage, mobilisation and liberation as free fatty acids
      (lipolysis). During these last few years, as well as this role as an energetic
      reserve which manages lipogenesis/lipolysis balance, the adipocyte has acquired
      the status of an endocrine and paracrine cell through the identification of
      numerous secreted factors. When we look back at the history of slimming products
      launched on the market since the 1980's, we can notice the role of the adipocyte
      tool and understand its functions in the choice of active ingredients, the
      development of complementary actions, the importance of the texture, the
      evolution of methods used to evaluate the efficacy on human volunteers and of
      course, we must not forget the women satisfaction and the power of seduction
      through words.

PMID- 14567187
TI  - [Lipids and skin inflammation: role of phospholipases A2].
AB  - Phospholipases A2 (PLA2) are enzymes that catalyse the hydrolysis of
      glycerophospholipids at the sn-2 position, generating free fatty acids and
      lysophospholipids. At present, PLA2 family consists of 12 groups. PLA2 are
      involved in many pathophysiological processes such as barrier function,
      eicosanoid production, and inflammation. They are implicated in inflammatory
      diseases of the skin: psoriasis, eczema, atopy. The presence of PLA2 activity has
      been demonstrated several years ago, however the precise localization of all
      these PLA2 in the epidermis and its appendages has to be determined. Further
      studies have shown that these enzymes are expressed in various layers of
      epidermis. This differential localization suggests different roles for each PLA2
      in skin physiology and during inflammation.

PMID- 14567188
TI  - [Relationship between lipids and cutaneous immunity: example of the
      gangliosides].
AB  - Gangliosides are glycosphingolipids made of hydrophobic ceramides coupled to
      hydrophilic sialylated oligosaccharides. They belong to lipid rafts located on
      the outer leaflet of the plasma membrane and their oligosaccharide moieties are
      exposed on the cell surface. Gangliosides are shed as monomeric molecules from
      the plasma membrane by a largely unknown mechanism into the extracellular medium
      and they are synthesized de novo by the cells. The shed gangliosides bind to
      lipoproteins from which they are taken up by erythrocytes and leukocytes. The
      ganglioside enrichment of leukocytes results in an alteration in the transduction
      of activation signals, leading to an impaired cellular immunity.

PMID- 14567189
TI  - Response of melanoma tumor phospholipid metabolism to chloroethyle nitrosourea: a
      high resolution proton NMR spectroscopy study.
AB  - Phospholipid metabolism is tightly involved in tumor growth regulation and tumor
      cell survival. The response of phospholipid metabolism to chloroethyle
      nitrosourea treatment is investigated in a murine B16 melanoma model.
      Measurements of phospholipid derivatives are performed on intact tumor tissue
      samples using one- and two-dimensional proton NMR spectroscopy. During the tumor
      growth inhibition phase under treatment, tumors overexpress phosphocholine,
      phosphoethanolamine, glycerophosphocholine and glycerophosphoethanolamine,
      whereas phosphatidylcholine and phosphatidylethanolamine levels are maintained to
      control levels. During re-growth, which remained quantitatively much below
      control growth, chloroethyle nitrosourea-treated melanoma tumors overexpress
      phosphocholine and phosphoethanolamine only. In treated melanoma,
      phosphatidylcholine levels show an inverse relationship with tumor growth rates.
      In conclusion, chloroethyle nitrosourea-treated melanoma tumors maintain their
      phosphatidylcholine levels and exhibit transformed phospholipid metabolism
      phenotype, by mechanisms that could participate in tumor cell survival.

PMID- 14567190
TI  - [Cutaneous lipids: from physiology to the clinical].
AB  - The primary function of the epidermis is to produce the waterimpermeable stratum
      corneum that permits terrestrial life. Extracellular glycosylceramides are the
      main precursors of the stratum corneum ceramides which play a role in the
      cohesion of corneocytes and the establishment of the barrier function. The
      physiological desquamative process depends upon the transformation of
      glycosylceramides to ceramides and of cholesterol sulfate to cholesterol.
      Intracellular ceramides participate to the terminal differentiation process of
      the epidermis. Abnormalities in the synthesis and/or the secretory mechanisms of
      the epidermal lipids induce various skin disorders. Such diseases may have a
      genetic background or result from the influence of environmental factors.

PMID- 14567191
TI  - [Structural and ultrastructural data on human cutaneous lipids].
AB  - The principal function of intercellular lipids of the epidermal horny layer is
      the constitution of an occlusive barrier and regulation of transepidermal water
      fluxes. Self-assembly of lipid bilayers and formation of multilayered structures
      can be observed in the intercellular spaces of the stratum corneum. Progressive
      organisation of lipids provokes the lateral displacements of hydrophilic
      compartments, squeezed aside along the lipid layers towards intercellular
      junctions (corneodesmosomes). Proteolytic enzymes contained in the hydrophilic
      material are thus delivered to the extracellular portions of cohesive junctional
      proteins. Consequently, modifications of the composition and structure of the
      stratum corneum lipids may influence epidermal desquamation through the
      regulation of corneodesmosome accessibility to extracellular enzymes.

PMID- 14567192
TI  - [Biochemical analysis of epidermal lipids].
AB  - According to the knowledge acquired some 15 years ago, the cutaneous lipids may
      be classified into 2 families: the "neutral" lipids, represented by cholesterol,
      cholesterol esters, cholesterol sulphate, triglycerides, free fatty acids,
      squalen and alcanes, and the "polar" lipids including phospholipids
      (phosphatidylcholine, phosphatidylserine, phosphatidylethanolamine,
      sphingomyeline) and sphingolipids (ceramides I-VII, monohexosylceramides). From
      the functional point of view, free fatty acids, cholesterol, and ceramides
      organised in layers are the most important components of intercellular spaces of
      the stratum corneum. Analytic methods have been recently developed to help
      understand the structural organisation of these various molecules within the
      horny layer and their influence on the epidermal barrier function. Raman
      microspectroscopy or X-ray diffraction are most frequently used. Differential
      calorimetry and fluorescence or infrared spectroscopy provide complementary
      information. The principal findings are: lamellar structure depends on the
      presence of ceramides supplemented by adequate quantities of free fatty acids and
      cholesterol; ceramide chains interact to provide the ordered structure and
      ceramide-1 is necessary for stabilisation of lipid layers; cholesterol may
      regulate the molecular mobility of hydrocarbon chains within the bi-layers.
      Knowledge of the molecular structure of the barrier lipids finds several
      applications, e.g.: in pharmacology--conception of new formulations adapted for
      percutaneous and topical application of drugs; in dermatology--comprehension of
      physiopathologic mechanisms of various dermatoses; in biotechnology--development
      of skin substitutes with valid stratum corneum barrier; in cosmetics--choice of
      best formulations suited for reconstruction of the intercellular lipid substance.

PMID- 14567193
TI  - [Functional consequences of cutaneous lipid perturbation].
AB  - Epidermal lipids constitute an ultimate frontier between the organism and its
      environment. Their essential role consists of providing a barrier limiting both
      transepidermal water loss and penetration of external factors, such as irritants.
      Efficacy of the barrier depends on the physicochemical properties of the
      substance applied to the skin surface and the increase in transepidermal water
      loss, which may be quantified, is proportional to the provoked perturbation in
      the barrier function. In atopic dermatitis epidermis, a significant decrease in
      the ceramide content and abnormally low levels of omega-6 fatty acids correlate
      with an increased rate of water loss at the skin surface--a sign of an impaired
      barrier. However, similar signs are observed in the atrophic epidermis provoked
      by long term local corticotherapy. Epidermal lipid profiles are also seriously
      modified in various ichthyoses, and are partially responsible for the
      hyperkeratosis observed clinically, e.g.: the recessive X-linked form is provoked
      by a mutation of the steroid sulphatase gene and the resulting accumulation of
      unconverted precursor of cholesterol. Modification of the lipid composition in
      acne contributes to comedo formation, whereas UV improves barrier function (and
      may provoke hyperkeratosis) through an increase in the stratum corneum lipid
      content. Another source of lipids at the epidermal surface is sebaceous glands.
      Waxes present in the sebum increase friction coefficient of the skin surface.
      Sebum also influences (decreases) the rate of penetration of lipophilic
      substances applied on the skin. Its role in the skin biology appears to be less
      vital than that of the lipids constituting the permeability barrier of the
      stratum corneum.

PMID- 14567194
TI  - [Normal and pathologic sebaceous function. Research in a shallow milieu?].
AB  - Modern therapeutic approaches allow to control sebaceous secretion but knowledge
      about the sebaceous gland and its precise function within the pilosebaceous unit
      is still insufficient. Steroid hormones are the principal albeit not exclusive
      regulators of the sebaceous glands. Three phases may be distinguished in
      sebaceous physiology: secretion-production, stocking in the follicular reservoir,
      and excretion. Human "native" intracellular sebum, before secretion, is composed
      of squalene, waxes, and triglycerides. Once secreted, the sebum is colonised by
      various xenobiots whose development is controlled by several defensive humoral
      mechanisms and by the contact with ambient oxygen. Oxygen and micro-organisms
      transform "native" sebum, lysis of triglycerides to fatty acids being the most
      pronounced activity. Certain components of this complex mixture of molecules
      present in the sebum are clearly cytotoxic or irritant, provoking reactive
      follicular hyperkeratosis and comedone formation--the first step to acne. Some
      lipophilic organisms like Malassezia yeast may be highly antigenic and induce
      chronic inflammatory reactions like in seborrhoeic dermatitis. Demodex is an
      inrafollicular parasite feeding on sebum that frequently causes blepharitis.
      Sebum is also a vehicle transporting and transmitting several endogenous and
      exogenous molecules, including potential regulatory factors of hair follicles.
      Recent development of in vitro cultures of functional sebocytes should help to
      better understand several aspects of the sebaceous gland's biology.

PMID- 14567195
TI  - [Liposomes and skin: past, present, future].
AB  - tAmong various approaches to intra- and percutaneous administration of drugs,
      e.g. application of patches, ointments, iontophoresis, electroporation, the use
      of lipid vesicles like liposomes and niosomes presents numerous advantages. They
      are not toxic or invasive, may deliver hydrophobic and/or hydrophilic molecules,
      and the size of the transported molecule is not a limiting factor. Liposomes are
      obtained with natural amphiphilic lipids whereas niosomes are composed of
      synthetic amphiphilic molecules. These microscopic vesicles contain from one to
      several concentric lipid bi-layers with intercalated aqueous compartments. Trans
      epidermal penetration of the vesicles is proportional to the "fluidity" of their
      lipids and their negative charge. Several drugs and cosmetics in this gallenic
      form are already commercially available and successfully used, presenting a
      better dose/effect ratio and provoking less side-effects.

PMID- 14567196
TI  - [Molecular characterization and biodiversity of Mycobacterium tuberculosis in the
      Antilles-Guiana region and comparative analysis in a metropolitan region,
      Aquitaine].
AB  - Tuberculosis is a highly contagious infectious disease in recrudescence whose
      epidemiologic monitoring is reinforced by molecular biology. In this context, we
      were particularly interested in the cases of tuberculosis of French West Indies
      and French Guiana (FWI-FG). This study covered a period of two years (1997 and
      1998) and focused on the demographical and epidemiological characteristics of the
      cases diagnosed by an analysis of their genotypes. Our results were confronted
      with a French metropolitan area (Aquitaine) with similar demographic background.
      Moreover, Aquitaine area has privileged links with FWI-FG region and also has a
      similar network for monitoring tuberculosis as ours. So we used a PCR method
      called spoligotyping as a first line method to optimize the alternative IS6110
      RFLP method which remains cumbersome. A total of 105 strains of FWI-FG and 172
      strains of Aquitaine were typed by spoligotyping and by the standard IS6110-RFLP
      method. The results of the first grouping by spoligotyping were analyzed in
      comparison with IS6110-RFLP. The results obtained showed a rate of recent
      transmission of tuberculosis being 34.3% in FWI-FG and 10.5% in Aquitaine. These
      observations underlined a high degree of polymorphism in the Aquitaine region as
      compared to the FWI-FG region. Thanks to the various profiles obtained by
      spoligotyping, we could study their distribution in the three areas and highlight
      common types like type 53, 50 and 42 and types found locally like the types 33
      and 14 found respectively in Aquitaine and FWI as well as endemic types like type
      76 found only in FG. These results are discussed in the context of the evolution
      of clinical isolates of tubercle bacilli with time.

PMID- 14567197
TI  - [Phenotypes of beta-lactam resistance in the genus Aeromonas].
AB  - This work aimed to investigate resistance profiles towards beta-lactam
      antibiotics in correlation with beta-lactamases production in the genus
      Aeromonas. In a series of 417 wild-type strains, biochemical identification and
      testing with 11 beta-lactams by the disk-diffusion method revealed 5 predominant
      phenotypes: A. hydrophila complex/class B, C and D beta-lactamases; A. caviae
      complex/class C and D beta-lactamases; A. veronii complex/class B and D beta
      lactamases; A. schubertii spp./class D beta-lactamase; A. trota spp./class C beta
      lactamase. A subgroup of 64 representative strains was submitted to MIC
      determination with 8 beta-lactam compounds alone and in combination with 3 beta
      lactamase inhibitors (clavulanic acid, tazobactam and BRL 42715). Visualisation
      of beta-lactamases and pI determination were performed in all these 64 isolates
      by isoelectric focusing from crude extracts. The different Aeromonas species
      produced 1 to 3 of the following inducible enzymes: an imipenemase with low
      expression, which is difficult to detect with routine phenotype studies (class B,
      pI 8, imipenem MIC > 2 micrograms/ml), a cephalosporinase (class C, pI > 7 +/-
      0.5, cephalothin MIC > 256 micrograms/ml), and an oxacillinase widely produced in
      the genus Aeromonas (class D, pI > 8.5, ticarcillin MIC > 256 micrograms/ml). In
      Aeromonas spp. resistance profile to beta-lactam antibiotics is correlated with
      naturally occurring phenotypes of beta-lactamases production. As a conclusion,
      the characterisation of these different enzymes is of therapeutic and taxonomic
      interest, in species notoriously difficult to identify.

PMID- 14567198
TI  - [Autoantibodies, tolerance and autoimmunity].
AB  - In 1900, the group from Metchnikoff suggested the concept of autoimmunization by
      demonstrating the presence of autoantibodies in normal conditions; which was
      opposed to the concept of horror autotoxicus raised by Ehrlich. Landsteiner's
      description of the transfusion compatibility rules and 50 year-later work from
      Burnett's and Medawar's groups lead to the clonal deletion theory as a general
      explanation of tolerance and autoimmunity. However, more recent work succeeded
      demonstrating that autoreactive B cells constitute a substantial part of the B
      cell repertoire and that this autoreactive repertoire secretes the so-called
      natural autoantibodies (NAA) characterized by their broad reactivity mainly
      directed against very well conserved public epitopes. They fulfill the definition
      of an autoantibody since they are self-reactive, but they are not self-specific.
      As yet, NAA directed against determinants of polymorphism have not been reported.
      The presence of this repertoire in normal conditions challenges the clonal
      deletion theory as a unique explanation for self-tolerance. However, if we take
      into account that this autoreactive B-cell repertoire is not self-specific, this
      contradiction may not be a real one opposition. Indeed, the Lansteiner's rule
      that a subject belonging to group A will never produce anti-A antibodies and will
      always produce natural antibodies against the B-cell group, could never be
      challenged. Clonal deletion is probably accounting for this phenomenum. However,
      the serum of healthy adult individuals frequently exhibits low titers of anti-I
      antibodies, which is a precursor molecule of AB0 antigen system. The mechanism
      accounting for deletion of B cells directed against critical determinants like
      antigens A and B in the red blood cell system and allowing the production of
      autoantibodies against I remain elusive.

PMID- 14567199
TI  - Comprehensive analysis and management of chronic pain.
AB  - Given the pervasive effect of chronic pain, a comprehensive approach to nursing
      care is needed. Addressing the physical effects of persistent pain on multiple
      systems and bodily functions requires combining (drug and nondrug) interventions
      to reduce pain and improve functioning. Targeting anxiety, depression and anger
      effectively can halt or even reverse the escalation of pain attributed to
      emotions. Recognizing belief patterns associated with distress and disability,
      while challenging patients to rethink the truthfulness of their perceptions is an
      important step in helping patients think, feel, and do better. Eliciting self
      reflective narratives about the context of pain in their lives taps into the
      spiritual domain and initiates processes of grieving, forgiveness, and acceptance
      that are needed to transcend perceived limits and find new meaning in their
      lives. By attending to social interactions, including therapeutic relationships,
      chronic pain patients can become more independent and involved in family or
      socially meaningful activities. Combined, nurses can help patients restore joy,
      functioning, and a sense of purpose despite the devastating toll persistent pain
      has taken.

PMID- 14567200
TI  - Interventions to overcome clinician- and patient-related barriers to pain
      management.
AB  - Barriers to optimal cancer pain management exist among clinicians and patients,
      and within the healthcare system. This article focuses on clinician- and patient
      related barriers and the interventions that have been tested to overcome them.
      Although individual studies have shown promise in improving patient outcomes,
      overall the studies do not provide clear answers to guide practice. Further
      research is required to determine what components of educational interventions
      are necessary to facilitate optimal cancer pain management.

PMID- 14567201
TI  - The use of long-acting opioids in chronic pain management.
AB  - The consensus statement from the American Pain Society and American Academy of
      Pain Medicine states that the undertreatment of pain is unjustified [6]. It has
      been suggested that opioid therapy can be used effectively to treat noncancer
      pain in a subset of patients [26], and this is becoming more acceptable [3].
      Providing sustained analgesia is an important aspect of therapy, and medications
      should be administered on an around-the-clock basis, because regular
      administration of doses maintains a constant level of drug in the body and helps
      prevent recurrence of pain. Ideal treatment for persistent pain is a long-acting
      opioid administered around the clock to prevent baseline pain, with the use of
      short-acting opioids as supplemental agents for breakthrough pain. Controlled
      release formulations can lessen the inconvenience associated with around-the
      clock administration of short-acting opioids. Sustained analgesia also can be
      achieved with transdermal fentanyl, which combines a strong opioid with a 72-hour
      release profile and the benefits of a parenteral route, avoiding first-pass
      metabolism. Controlled-release formulations of morphine and oxycodone are
      available in the United States, and hydromorphone preparations are being reviewed
      for approval. Clinical experience with these formulations and transdermal
      fentanyl indicates that these agents are equally effective in controlling pain.
      Studies have demonstrated improved quality of life with the transdermal route and
      with controlled-release morphine and oxycodone. Because of patch reapplication
      every 72 hours, the transdermal route also enhances compliance. Use of an opioid
      without the need for oral or intravenous administration and the opportunity to
      improve compliance are among the advantages of the transdermal route in clinical
      practice. The nurse has an important role in the management of patients receiving
      long-acting opioids for chronic noncancer pain, Facilitation of the conversion
      from short-acting to long-acting opioids may be the initial step.
      Individualization of therapy to determine which route and product best suits the
      patient's needs and lifestyle can be accomplished through a comprehensive nursing
      assessment. Titration of dose along with institution of a short-acting opioid for
      break-through pain may require frequent interventions that a nurse familiar with
      the patient can provide. Prevention and management of opioid-related adverse
      events are essential for effective opioid therapy. Providing patient and family
      education regarding administration, monitoring, and management of opioid therapy
      is an important nursing role. Lastly, documentation of pain level, functional
      status, and opioid-related adverse events is required for each contact with the
      patient, to make this information available to all who assist in the management
      of the patient's pain. Chronic noncancer pain is an experience that affects all
      aspects of a patient's life. Effective pain management with long-acting opioids
      may help the patient to focus on the positive aspects of life, decreasing the
      focus on pain.

PMID- 14567202
TI  - Nonopioid and adjuvant analgesics in chronic pain management: strategies for
      effective use.
AB  - Nonopioid and adjuvant analgesics encompass a huge range of heterogenous drugs
      that differ chemically and mechanistically. These drugs generally are prescribed
      for mild-to-moderate pain, as coanalgesics for severe pain, or to target specific
      pain-generating mechanisms. This article provides an overview of some of the more
      commonly used nonopioid and adjuvant analgesics used to treat chronic pain,
      including salicylates, acetaminophen, nonsteroidal anti-inflammatory drugs,
      tricyclic antidepressants, anticonvulsants, N-Methyl-D-Aspartate receptor
      antagonists, lidocaine, skeletal muscle relaxants, and topical analgesics.

PMID- 14567203
TI  - Cognitive-behavioral therapy: tailored to the individual.
AB  - Cognitive-behavioral therapy focuses on the cognitive, affective, and behavioral
      components of the pain experience. Cognitive-behavioral strategies can be used to
      treat chronic pain and chronic intermittent pain. The strategies concentrate on
      emotional, behavioral, and social responses, helping patients to increase their
      feelings of control or feelings of self efficacy regarding control.

PMID- 14567204
TI  - Physical modalities in chronic pain management.
AB  - The following conclusions can be made based on review of the evidence: There is
      limited but positive evidence that select physical modalities are effective in
      managing chronic pain associated with specific conditions experienced by adults
      and older individuals. Overall, studies have provided the most support for the
      modality of therapeutic exercise. Different physical modalities have similar
      magnitudes of effects on chronic pain. Therefore, selection of the most
      appropriate physical modality may depend on the desired functional outcome for
      the patient, the underlying impairment, and the patient's preference or prior
      experience with the modality. Certain patient characteristics may decrease the
      effectiveness of physical modalities, as has been seen with TENS. These
      characteristics include depression, high trait anxiety, a powerful others locus
      of control, obesity, narcotic use, and neuroticism. The effect on pain by various
      modalities is generally strongest in the short-term period immediately after the
      intervention series, but effects can last as long as 1 year after treatment
      (e.g., with massage). Most research has tested the effect of physical modalities
      on chronic low back pain and knee OA. The effectiveness of physical modalities
      for other chronic pain conditions needs to be evaluated more completely. Older
      and younger adults often experience similar effects on their perception of pain
      from treatment with physical modalities. Therefore, use of these modalities for
      chronic pain in older adults is appropriate, but special precautions need to be
      taken. Practitioners applying physical modalities need formal training that
      includes the risks and precautions for these modalities. If practitioners lack
      formal training in the use of physical modalities, or if modality use is not
      within their scope of practice, it is important to consult with and refer
      patients to members of the team who have this specialized training. Use of a
      multidisciplinary approach to chronic pain management is of value for all adults
      and older individuals in particular [79-81]. Historically, physical therapists
      have been trained to evaluate and treat patients with the range of physical
      modalities discussed in this article. Although members of the nursing staff
      traditionally have used some of these modalities (e.g. some forms of heat or cold
      and massage), increasing numbers of nurses now are being trained to apply more
      specialized procedures (e.g., TENS). Healthcare professionals must be
      knowledgeable about the strength of evidence underlying the use of physical
      modalities for the management of chronic pain. Based on the limited research
      evidence available (especially related to assistive devices, orthotics, and
      thermal modalities), it often is difficult to accept or exclude select modalities
      as having a potential role in chronic pain management for adults and older
      individuals. Improved research methodologies are needed to address physical
      modality effectiveness better.

PMID- 14567205
TI  - Complementary and alternative therapies: what is their place in the management of
      chronic pain?
AB  - Nurses have used complementary therapies for many years to relieve anxiety,
      promote comfort, and reduce or alleviate pain. The therapies described in this
      article are examples of the many therapies available for nurses to consider when
      planning care for patients with chronic pain. The increasing body of scientific
      knowledge is providing more guidance about the efficacy of specific therapies. As
      with all interventions, ongoing evaluation about the effectiveness of a therapy
      for each patient is an important component of quality nursing care. Complementary
      therapies provide an avenue for nurses to be autonomous in furthering the relief
      of chronic pain, as many of these therapies fall within the domain of nursing.
      Incorporating selected therapies into the plan of care provides multiple
      opportunities for nurses to demonstrate caring, a premier characteristic of
      nursing. A number of the complementary therapies, such as journaling, hand
      massage, and imagery, can be taught to patients and their families, thus
      promoting self-care. Anecdotal evidence and findings from numerous smaller
      studies provide some support for the use of many complementary therapies to
      manage chronic pain or their use as adjuncts in the treatment regimen. Still, the
      nurse must weigh the risks and benefits before suggesting a therapy to a patient.
      Evaluating the effectiveness of the complementary therapy to promote comfort in
      patients with chronic pain is essential. Obtaining this information is not only
      critical to the care of a particular patient, but these data will assist nurses
      in learning more about specific therapies. Most importantly, nurses need to
      pursue research to further the scientific basis for many of the complementary
      therapies.

PMID- 14567206
TI  - Chronic pain in the workplace.
AB  - Chronic pain, especially chronic back pain, is costly to workers, their families,
      employers, and society. Successful return to productive work life for the worker
      with chronic pain requires multi-disciplinary efforts, including those of the
      nurse case manager, occupational health nurse, and nursing specialist in pain
      management. Sensitivity to the dynamics of multiple stakeholders in the RTW
      process is essential because of their diverse perspectives. Successful RTW can be
      facilitated by a combination of approaches, including case management, worker
      capacity evaluation, ergonomic job analysis, team design of job modifications,
      appropriate medical treatment, and self management by the worker.

PMID- 14567207
TI  - Chronic pain, substance abuse and addiction.
AB  - Health care professionals face numerous challenges in assessing and treating
      chronic pain patients with a substance abuse history. Societal perspectives on
      morality and criminality, imprecise addiction terminology, litigation fears, and
      genuine concern for a patient's relapse into or escalation of substance abuse
      result in unrelieved and under-relieved pain in precisely the population that--as
      increasing evidence indicates--is generally intolerant of pain. Before adequate
      pain relief can occur in chronic pain patients with current or past substance
      abuse issues, it is imperative that the clinician recognize addiction as a
      disease with known symptoms and treatments. Further, the clinician must realize
      the difference between true addiction and similar conditions, so the patient's
      condition can be monitored and regulated properly. Although clinicians are often
      reluctant to medicate with opioids, it is always best to err on the side of
      adequate pain relief. Withholding opioids from chronic pain patients in order to
      avoid the onset or relapse of addiction is contrary to the growing body of
      evidence and results only in unnecessary pain for the patient. Chronic pain in
      patients with a history of addictive disease can be treated successfully with
      opiate analgesia; it just requires caution and careful monitoring of medication
      use. If addiction is treated as a known risk when providing opioid analgesia to a
      recovering addict, its development can be minimized while pain relief is
      provided.

PMID- 14567208
TI  - The complex pain patient: interventional treatment and nursing issues.
AB  - This article discusses interventional treatment for the complex pain patient,
      including intraspinal opioid administration spinal cord stimulation, and commonly
      performed nerve blocks. The role of the nurse has grown to support these
      technological interventions, and nursing has provided a foundation to strengthen
      the success of these interventions through watchful monitoring and patient
      education.

PMID- 14567209
TI  - Antibodies to phocine herpesvirus-1 are common in North American harbor seals
      (Phoca vitulina).
AB  - Phocine herpesvirus-1 (PhHV-1) has been associated with morbidity and high
      mortality in neonatal harbor seals (Phoca vitulina) along the Pacific coast of
      California (USA) and in northern Europe. Seals dying with PhHV-1 associated
      disease in California primarily have histopathologic evidence of adrenal necrosis
      or adrenalitis with herpesviral inclusion bodies. Little is known about
      prevalence of exposure to PhHV-1, modes of disease transmission, and viral
      pathogenesis in free-ranging harbor seal populations. To evaluate the prevalence
      in North America, 866 serum samples collected between 1994 and 2002 from harbor
      seals captured or stranded on the Pacific and Atlantic coasts of North America
      were assayed by enzyme linked immunosorbent assay (ELISA) for evidence of PhHV-1
      exposure. Samples from three harbor seal age classes (pre-weaned, weaned, and
      subadults/adults) were obtained from each of four regions to compare exposure
      among sex, age class, and region. We found increasing prevalence with age as
      37.5% of pre-weaned pups, 87.6% of weaned pups, and 99.0% of subadults and adults
      were seropositive. When accounting for age, no associations between
      seropositivity and sex or location of harbor seals were detected. These data
      indicate that PhHV-1 is endemic in the harbor seal populations of North America.

PMID- 14567210
TI  - Patterns of mortality in southern sea otters (Enhydra lutris nereis) from 1998
      2001.
AB  - Detailed postmortem examination of southern sea otters (Enhydra lutris nereis)
      found along the California (USA) coast has provided an exceptional opportunity to
      understand factors influencing survival in this threatened marine mammal species.
      In order to evaluate recent trends in causes of mortality, the demographic and
      geographic distribution of causes of death in freshly deceased beachcast sea
      otters necropsied from 1998-2001 were evaluated. Protozoal encephalitis,
      acanthocephalan-related disease, shark attack, and cardiac disease were
      identified as common causes of death in sea otters examined. While infection with
      acanthocephalan parasites was more likely to cause death in juvenile otters,
      Toxoplasma gondii encephalitis, shark attack, and cardiac disease were more
      common in prime-aged adult otters. Cardiac disease is a newly recognized cause of
      mortality in sea otters and T. gondii encephalitis was significantly associated
      with this condition. Otters with fatal shark bites were over three times more
      likely to have pre-existing T. gondii encephalitis suggesting that shark attack,
      which is a long-recognized source of mortality in otters, may be coupled with a
      recently recognized disease in otters. Spatial clusters of cause-specific
      mortality were detected for T. gondii encephalitis (in Estero Bay),
      acanthocephalan peritonitis (in southern Monterey Bay), and shark attack (from
      Santa Cruz to Point Ano Nuevo). Diseases caused by parasites, bacteria, or fungi
      and diseases without a specified etiology were the primary cause of death in
      63.8% of otters examined. Parasitic disease alone caused death in 38.1% of otters
      examined. This pattern of mortality, observed predominantly in juvenile and prime
      aged adult southern sea otters, has negative implications for the overall health
      and recovery of this population.

PMID- 14567211
TI  - Prevalence of skeletal and eye malformations in frogs from north-central United
      States: estimations based on collections from randomly selected sites.
AB  - Skeletal malformation rates for several frog species were determined in a set of
      randomly selected wetlands in the north-central USA over three consecutive years.
      In 1998, 62 sites yielded 389 metamorphic frogs, nine (2.3%) of which had
      skeletal or eye malformations. A subset of the original sites was surveyed in the
      following 2 yr. In 1999, 1,085 metamorphic frogs were collected from 36 sites and
      17 (1.6%) had skeletal or eye malformations, while in 2000, examination of 1,131
      metamorphs yielded 16 (1.4%) with skeletal or eye malformations. Hindlimb
      malformations predominated in all three years, but other abnormalities, involving
      forelimb, eye, and pelvis were also found. Northern leopard frogs (Rana pipiens)
      constituted the majority of collected metamorphs as well as most of the malformed
      specimens. However, malformations were also noted in mink frogs (R.
      septentrionalis), wood frogs (R. sylvatica), and gray tree frogs (Hyla spp.). The
      malformed specimens were found in clustered sites in all three years but the
      cluster locations were not the same in any year. The malformation rates reported
      here are higher than the 0.3% rate determined for metamorphic frogs collected
      from similar sites in Minnesota in the 1960s, and thus, appear to represent an
      elevation of an earlier baseline malformation rate.

PMID- 14567212
TI  - A forty-three year museum study of northern cricket frog (Acris crepitans)
      abnormalities in Arkansas: upward trends and distributions.
AB  - The northern cricket frog (Acris crepitans) is a resident of streams, rivers, and
      wetlands of eastern North America. We documented abnormalities in A. crepitans
      housed in the Arkansas State University Museum of Zoology Herpetology Collection.
      Abnormality frequency increased from 1957 to 2000 (chi 2 = 43.76, df = 3, P <
      0.001). From 1957 through 1979 only 3.33% of specimens were unusual. This rate
      was 6.87% during the 1990s, and in 2000 it was 8.48%. High frequencies of
      abnormalities were identified in the following Ozark highland counties: Sharp,
      Lawrence, and Randolph. We observed 104 abnormalities among 1,464 frogs (7.10%).
      The differential abnormality frequencies observed between the Arkansas lowlands
      and highlands are striking. The Ozarks had significantly higher frequencies of
      abnormalities than other Arkansas regions (chi 2 = 59.76, df = 4, P < 0.001). The
      Ouachita Mountains had significantly higher frequencies than the Gulf Coastal
      Plain, Delta, or Arkansas River Valley (chi 2 = 13.172, df = 3, P < 0.01). There
      was no difference in abnormality frequency between the Gulf Coastal Plain, Delta,
      and Arkansas River Valley (chi 2 = 0.422, df = 2, P > 0.70). Proposed hypotheses
      for distributions include: 1) A. crepitans might possess naturally high
      abnormality levels, and land use practices of the Delta may reduce this
      variability; 2) an unknown xenobiotic may be in Ozark streams causing increased
      numbers of abnormalities; 3) the museum's collection effort may be skewed; 4)
      Delta habitat might be more favorable for green tree frogs (Hyla cinerea)
      allowing this species to drive out A. crepitans through competition; here,
      abnormal metamorphs are not detected because they are even less competitive than
      normal individuals.

PMID- 14567213
TI  - Detection of feline coronavirus infection in southern African nondomestic felids.
AB  - Feline coronavirus (FCoV) infects members of the Felidae family with results
      ranging from seroconversion with no disease to fatal feline infectious
      peritonitis (FIP). Infection of non-domestic felids with FCoV is of concern,
      particularly in endangered populations such as cheetahs (Acinonyx jubatus). In
      this investigation, we tested 342 animals in the Republic of South Africa and
      Namibia, including 140 animals from wild populations, for evidence of FCoV
      infection by serology and/or reverse transcription/nested polymerase chain
      reaction (RT/nPCR) on feces from 1999 through 2001. Past or current infection was
      evaluated. Of these, 195 animals had evidence of infection and included 41
      animals from wild populations. Serology (indirect immunofluorescence) did not
      always correlate with viral RNA detection, as seronegative animals were
      occasionally virus-positive, while many seropositive animals were not shedding
      virus. Serology indicated the infecting virus was most closely related to type I
      FCoV. Antibody levels in the majority of animals were low, even in those actively
      infected. Ten of 48 animals tested at more than one time point by RT/nPCR were
      shedding virus at multiple time points possibly indicating persistent infection.
      Infection in free-ranging animals was also notable, as over a quarter of the free
      ranging animals tested had evidence of current or previous FCoV infection.
      Testing by serology and RT/nPCR is recommended for screening for FCoV infection.

PMID- 14567214
TI  - Characterization of Pasteurella multocida associated with pneumonia in bighorn
      sheep.
AB  - Pasteurella multocida is a highly diverse group of bacteria recognized as
      important pathogens. Although P. multocida is not ordinarily associated with
      disease in Rocky Mountain bighorn sheep (Ovis canadensis canadensis), numerous
      isolates were cultured in high numbers from free-ranging bighorn sheep in the
      Hells Canyon area of Idaho, Washington, and Oregon (USA) during the winter of
      1995-96. Animals captured in Hells Canyon and held in captivity, and their
      offspring, also harbored P. multocida. Biochemical utilization tests on 90
      isolates identified three subspecies: P. multocida multocida a (n = 54); P.
      multocida multocida b (n = 13); and P. multocida gallicida (n = 15); and a non
      speciated biotype, U6 (n = 8). Genomic DNA digestion with restriction
      endonuclease Hha I separated the isolates into 62 unique restriction fragment
      length polymorphism profiles. Capsular type A was predominant (72% of isolates).
      Only one isolate type, which may have been transmitted from a feral goat, was
      capsular type D, possessed the structural gene, toxA, for dermonecrotoxin
      detected by polymerase chain reaction, and produced toxin as determined by
      monoclonal antibody immunoblot. In conclusion, bighorn sheep in this study
      carried diverse types of generally non-toxigenic P. multocida associated with
      epizootic pneumonia.

PMID- 14567215
TI  - Immune responses after oral inoculation of weanling bison or beef calves with a
      bison or cattle isolate of Mycobacterium avium subsp. paratuberculosis.
AB  - Paratuberculosis is endemic in domestic and wild ruminants worldwide. We designed
      the following study to compare host immune responses and pathologic changes in
      beef calves and bison calves after challenge with either a cattle or bison (Bison
      bison) strain of Mycobacterium avium subsp. paratuberculosis. In the first part
      of the study, six bison and six beef calves were orally inoculated with a cattle
      isolate of M. avium subsp. paratuberculosis over a 2 wk period. In the second
      part, an additional six bison and six beef calves were similarly inoculated with
      a bison strain of M. avium subsp. paratuberculosis. Throughout each of the
      studies, blood and fecal samples were taken monthly for a 6 mo infection period.
      Tissue samples were obtained at necropsy for culture and histopathologic
      analyses. Results from this study demonstrated that bison calves were more
      susceptible to tissue colonization than beef calves after challenge with the
      cattle isolate and, conversely, that beef calves were more susceptible to the
      bison strain of M. avium subsp. paratuberculosis. Although lesions were minimal
      they were most apparent in the jejunum and distal ileum. Interferon-gamma (IFN
      gamma) responses were noted in some calves by 1 mo postinoculation and were
      sustained longer in beef calves after challenge with the bison isolate. Antibody
      was not detected in either beef or bison calves during the 6 mo infection period.
      These results indicate that the host response to strains of M. avium subsp.
      paratuberculosis may differ between ruminant species.

PMID- 14567216
TI  - Diagnostic and molecular evaluation of three iridovirus-associated salamander
      mortality events.
AB  - In 1998 viruses were isolated from tiger salamander larvae (Ambystoma tigrinum
      diaboli and A. tigrinum melanostictum) involved in North Dakota and Utah (USA)
      mortality events and spotted salamander (A. maculatum) larvae in a third event in
      Maine (USA). Although sympatric caudates and anurans were present at all three
      sites only ambystomid larvae appeared to be affected. Mortality at the North
      Dakota site was in the thousands while at the Utah and Maine sites mortality was
      in the hundreds. Sick larvae were lethargic and slow moving. They swam in circles
      with obvious buoyancy problems and were unable to remain upright. On the ventral
      surface, near the gills and hind limbs, red spots or swollen areas were noted.
      Necropsy findings included: hemorrhages and ulceration of the skin, subcutaneous
      and intramuscular edema, swollen and pale livers with multifocal hemorrhage, and
      distended fluid-filled intestines with areas of hemorrhage. Light microscopy
      revealed intracytoplasmic inclusions, suggestive of a viral infection, in a
      variety of organs. Electron microscopy of ultra thin sections of the same tissues
      revealed iridovirus-like particles within the inclusions. These viruses were
      isolated from a variety of organs, indicating a systemic infection.
      Representative viral isolates from the three mortality events were characterized
      using molecular assays. Characterization confirmed that the viral isolates were
      iridoviruses and that the two tiger salamander isolates were similar and could be
      distinguished from the spotted salamander isolate. The spotted salamander isolate
      was similar to frog virus 3, the type species of the genus Ranavirus, while the
      tiger salamander isolates were not. These data indicate that different species of
      salamanders can become infected and die in association with different
      iridoviruses. Challenge assays are required to determine the fish and amphibian
      host range of these isolates and to assess the susceptibility of tiger and
      spotted salamanders to heterologous virus isolates.

PMID- 14567218
TI  - Prion protein gene heterogeneity in free-ranging white-tailed deer within the
      chronic wasting disease affected region of Wisconsin.
AB  - Chronic wasting disease (CWD) was first identified in Wisconsin (USA) in
      whitetailed deer (Odocoileus virginianus) in February 2002. To determine if prion
      protein gene (Prnp) allelic variability was associated with CWD in white-tailed
      deer from Wisconsin, we sequenced Prnp from 26 CWD-positive and 100 CWD-negative
      deer. Sequence analysis of Prnp suggests that at least 86-96% of the white-tailed
      deer in this region have Prnp allelic combinations that will support CWD
      infection. Four Prnp alleles were identified in the deer population, one of
      which, resulting in a glutamine to histidine change at codon 95, has not been
      previously reported. The predominant allele in the population encodes for
      glutamine at codon 95, glycine at codon 96, and serine at codon 138 (QGS). Less
      abundant alleles encoded QSS, QGN, and HGS at the three variable positions.
      Comparison of CWD-positive with CWD-negative deer suggested a trend towards an
      over-representation of the QGS allele and an under-representation of the QSS
      allele.

PMID- 14567217
TI  - Potential sites of virus latency associated with indigenous pseudorabies viruses
      in feral swine.
AB  - Free-ranging feral swine (Sus scrofa) are known to be present in at least 32
      states of the USA and are continuously expanding their range. Infection with
      pseudorabies virus (PRV) occurs in feral swine and the primary route of
      transmission in free-living conditions seems to be venereal. Between 1995 and
      1999, naturally infected feral swine and experimentally infected hybrid progeny
      of feral and domestic swine, were kept in isolation and evaluated for occurrence
      of latent PRV indigenous to feral swine in sacral and trigeminal ganglia and
      tonsil. Sacral ganglia were shown, by polymerase chain reaction (PCR)
      amplification of the thymidine kinase (TK) gene of PRV, to be the most frequent
      sites of latency of PRV. Nine (56%) of 16 sacral ganglia, seven (44%) of 16
      trigeminal ganglia, and five (39%) of 13 tonsils from naturally infected feral
      swine were positive for PCR amplification of TK sequences of PRV. These tissues
      were negative for PRV when viral isolation was attempted in Vero cells. DNA
      sequencing of cloned TK fragments from the sacral ganglia of two feral swine,
      showed only one nucleotide difference between the two fragments and extensive
      sequence homology to fragment sequences from various domestic swine PRV strains
      from China, Northern Ireland, and the USA. The hybrid feral domestic swine,
      experimentally inoculated with an indigenous feral swine PRV isolate by either
      the genital or respiratory route, acquired the infection but showed no clinical
      signs of pseudorabies. Virus inoculated into either the genital or respiratory
      tract could, at times, be isolated from both these sites. The most common latency
      sites were the sacral ganglia, regardless of the route and dose of infection in
      these experimentally infected hybrids. Nine of 10 sacral ganglia, six of 10
      trigeminal ganglia, and three of 10 tonsils were positive for PCR amplification
      of TK sequences. No virus was isolated from these tissues in Vero cells. The
      demonstration of the sacral ganglia as the most common sites of latency of
      pseudorabies viruses indigenous to feral swine, supports the hypothesis that
      these viruses are primarily transmitted venereally, and not by the respiratory
      route as is common in domestic swine, in which the trigeminal ganglia are the
      predominant sites of virus latency.

PMID- 14567219
TI  - Patterns of Haemoproteus beckeri parasitism in the gray catbird (Dumatella
      carolinensis) during the breeding season.
AB  - We determined the prevalence and intensity of blood parasites in breeding gray
      catbirds (Dumatella carolinensis) at Killbuck Wildlife Area in Wayne and Holmes
      Counties, Ohio (USA) from June through August 2000. Of 98 catbirds sampled, 40
      (40.8%) had detectable infections of Haemoproteus beckeri. Overall prevalence of
      H. beckeri in this population is high relative to that reported in earlier blood
      parasite surveys of both breeding and migrant catbirds. Mean intensity of H.
      beckeri infection did not vary significantly between young and old birds or among
      sampling periods. We found no effect of age on prevalence or intensity of H.
      beckeri infection. Older birds were not more likely to be infected than younger
      birds, despite longer exposure to arthropod vectors. Prevalence varied
      significantly with season and was highest in June and lowest in August. This
      pattern also was observed in older birds sampled repeatedly. This seasonal
      variation may reflect both newly acquired infections and chronic infections
      relapsing in response to hormonal changes associated with breeding. Evidence of
      transmission was observed in the single hatching year bird that lacked detectable
      infection in early summer, but demonstrated a very high intensity infection in
      late summer. These observations provide supportive evidence that hematozoa
      infections are acquired on the breeding grounds during the first year of life and
      relapse during the breeding season in subsequent years.

PMID- 14567220
TI  - Meningeal worm in a reintroduced elk population in Kentucky.
AB  - Meningeal worm (Parelaphostrongylus tenuis) has been implicated in the failure of
      several elk (Cervus elaphus) restoration attempts in the eastern United States.
      However, limited post-release monitoring and a paucity of published literature
      prevents a clear understanding of this parasite's role in past failures. During
      winters of 1997-2001, the Kentucky Department of Fish and Wildlife Resources
      translocated 1,044 elk from western states to eastern Kentucky (USA) in an effort
      to restore a free-ranging population. We monitored 521 radio-collared elk over 4
      yr to determine the impact meningeal worm had on population establishment. Thirty
      (23%) of 129 non-capture related mortalities were attributed to meningeal worm.
      Twenty-two (73%) of these meningeal worm-caused mortalities were animals < 3 yr
      old. If younger elk born in Kentucky suffer higher mortality rates than older
      translocated elk, the population growth observed during the initial years of
      restoration may be temporary. Additional research is necessary to determine the
      influence meningeal worm will have on elk population growth in Kentucky.

PMID- 14567221
TI  - Canine heartworms in coyotes in Illinois.
AB  - Canine heartworm (Dirofilaria immitis) disease affects wild canids and may be a
      factor impacting the health and population dynamics of coyotes (Canis latrans).
      Coyotes may serve also as a potential reservoir for transmission of these
      parasites to domestic dogs. We investigated 920 coyotes harvested by hunters and
      trappers throughout Illinois (USA) from 1995-1997. The objectives of the study
      were to: 1) survey the regional prevalence and intensity of heartworms in coyotes
      in Illinois, 2) determine whether heartworm intensity correlates with physical
      condition, particularly body weight and winter fat levels, and 3) evaluate the
      relationship between heartworm infections and the reproductive success of
      females. Prevalence of heartworms statewide was 16.0%. Prevalence was
      significantly higher in males (17.7%) than in females (14.1%; P = 0.04) and was
      higher in the older age-classes (P < 0.0001). The regional prevalence of
      heartworms increased from northern to southern Illinois. Intensity ranged from 1
      to 111 with a mean of 8.7 (SD = 13.2) worms. Intensities did not differ
      significantly between sexes (P = 0.53) or among age-classes (P = 0.84). Most
      infected coyotes had low intensity infections, 78.2% carried < 12 heartworms,
      11.6% had 12-24 worms, and 10.2% were infected with > 24 worms. Body weights were
      not correlated with the presence of heartworms, nor were levels of kidney fat and
      marrow fat. However, reproductive success was lower in infected females. The
      percent of yearling females that bred was lower among infected females, as was
      the number of offspring produced by adults > or = 3.5 yr old. Our study
      demonstrates that heavy infections adversely affect fur quality and reduce
      fecundity of some females, but these effects are small and few coyotes (4.1%) had
      enough worms to trigger them. Coyote populations have increased in Illinois
      during the past 20 yr, but prevalence and intensity of heartworm disease appears
      to have changed little in that period. We conclude that heartworm disease is only
      a minor factor influencing coyote population dynamics in Illinois.

PMID- 14567222
TI  - Hematology and serum chemistry comparisons between free-ranging and rehabilitated
      harbor seal (Phoca vitulina richardsi) pups.
AB  - The objectives of this study were to compare the hematology and serum chemistry
      values between free-ranging and stranded harbor seal (Phoca vitulina richardsi)
      pups and to ascertain how blood values of stranded pups changed during the
      rehabilitation process. Coincident with these comparisons, reference values were
      obtained for free-ranging pups. Stranded harbor seal pups (n = 28) recovered from
      areas between Pebble Beach and Moss Landing, California (USA) were admitted to
      The Marine Mammal Center, Sausalito, from March to May 1995, 1996, and 1998.
      Blood samples were collected from harbor seal pups before and after
      rehabilitation. As a control group, wild harbor seal pups were captured at Pebble
      Beach and Elkhorn Slough (n = 42) during the 1995, 1996, and 1998 pupping
      seasons. Mean eosinophil and calcium values of wild pups were significantly
      greater than those of newly admitted pups, whereas mean bands, aspartate
      aminotransferase, alanine aminotransferase, total bilirubin, and chloride values
      were significantly lower (P < or = 0.05). Mean neutrophil, band, lymphocyte,
      eosinophil, basophil, calcium, phosphorus, blood urea nitrogen, potassium, total
      protein, and globulin values of rehabilitated pups increased significantly after
      2-3 mo in captivity, whereas, mean red blood cell, hemoglobin, hematocrit,
      cholesterol, and total bilirubin values decreased significantly (P < or = 0.05).

PMID- 14567223
TI  - Copper status of muskoxen: a comparison of wild and captive populations.
AB  - We compared wild muskoxen (Ovibos moschatus) on Banks Island (Northwest
      Territories, Canada) with captive animals maintained on grass (Bromus sp.) hay
      and supplemental minerals. We measured copper (Cu) in liver, whole serum, and
      deproteinated serum (unbound Cu) as well as serum activity of the Cu-enzyme
      ceruloplasmin. Unbound serum Cu concentrations did not change with season in
      captive animals (n = 53). Ceruloplasmin activity was similar between seasons in
      females but elevated in males during breeding in autumn. Increasing
      concentrations of Cu in whole sera were mainly associated with protein whereas
      unbound Cu predominated at low concentrations of whole serum Cu. Ceruloplasmin
      activity and serum Cu concentration were linearly related to liver Cu in female
      muskoxen. Measures of copper status in females were lower in the wild (n = 19)
      than in captivity (n = 16): 8 vs. 160 ug Cu.g-1 of whole liver; 0.67 vs. 1.15
      microgram unbound Cu.ml-1 whole serum and; 22 vs. 33 IU.l-1 ceruloplasmin
      activity. Bioavailability of Cu may limit the population on Banks Island
      especially when density of animals is high. The wide range of hepatic Cu
      concentrations in muskoxen indicated accumulation of Cu without apparent ill
      effect in captive animals. Hepatic storage of Cu may allow wild muskoxen to
      contend with low and fluctuating availability of Cu in small foraging areas at
      high latitudes.

PMID- 14567224
TI  - Estimation of carcass fat and protein in northern pintails (Anas acuta) during
      spring migration.
AB  - Foraging in stopover areas influences nutritional condition of birds during
      spring migration. Our purpose was to determine if body mass, percent carcass
      water, and serum biochemistry would predict energy reserves (carcass fat and
      protein) in northern pintails (Anas acuta) at a spring staging area, Lake St.
      Pierre in Quebec, Canada (46 degrees 11 'N, 73 degrees 08 'W). Northern pintails
      were collected during spring 1997 (14 April-9 May). In this staging area, body
      mass and percent body water successfully estimated carcass protein and fat in
      male northern pintails, but only carcass protein in females. None of the seven
      blood parameters we used accurately estimated nutritional reserves in staging
      northern pintails. These findings suggest that investigators must use direct
      estimates of carcass reserves to examine nutrient reserve requirements for egg
      production, migration, or body maintenance during spring migration.

PMID- 14567225
TI  - Age-dependent changes in plasma and brain cholinesterase activities of house
      wrens and European starlings.
AB  - We determined age-dependent changes in plasma and brain cholinesterase (ChE)
      activity for two species of passerines: house wren (Troglodytes aedon) and
      European starling (Sturnus vulgaris, starling). In plasma from nestlings of both
      species, total ChE activity increased with age, acetycholinesterase (AChE, EC
      3.1.1.7) activity declined rapidly immediately after hatching, and
      butyrylcholinesterase (BChE, EC 3.1.1.8) activity increased steadily. For both
      species, total ChE and BChE activities and the BChE:AChE ratio in plasma were
      significantly greater in adults than nestlings suggesting trends observed in
      nestlings continue post fledging. In older nestlings and adults, AChE activity in
      plasma was significantly greater and BChE:AChE ratio less in house wrens than
      starlings. For house wrens as compared with starlings, ChE activity in brain
      increased at a significantly greater rate with age in nestlings and was
      significantly greater in adults. However, ChE activity in brain was similar at
      fledging for both species suggesting that the increase in ChE in brain is more
      directly related to ontogeny than chronologic age in nestlings of passerines. For
      both species, ChE activity increased significantly with brain weight of nestlings
      but not adults. House wrens hold similar patterns of age-dependent change in ChE
      activity in common with starlings but also exhibit differences in AChE activity
      in plasma that should be considered as a factor potentially affecting their
      relative toxicologic response to ChE inhibitors.

PMID- 14567226
TI  - Acute toxicity of lead, steel, and an iron-tungsten-nickel shot to mallard ducks
      (Anas platyrhynchos).
AB  - Twenty mallards (Anas platyrhynchos) of both sexes were dosed by oral gavage with
      Heavi-Shot (H-S; Environ-Metal, Inc., Sweet Home, Oregon, USA) pellets, 20 with
      steel shot, and 10 with lead (Pb) pellets, all of equal size. All pellets were
      fired from a shotgun into an absorbent material, retrieved, and weighed prior to
      introduction into the ducks. Birds were fed whole kernel corn and grit and
      observed for signs of toxicity for 30 days following dosing. Hevi-Shot pellets
      lost an average of 6.2% of their mass and steel shot pellets lost 57% of their
      mass in the birds' gizzards. Almost all (90%) of the Pb shot dosed birds died
      before the end of the study, while no mortality was observed in the steel or H-S
      dosed groups. Even though total food consumption differed between the H-S and
      steel shot groups, mean bird weight change was not different. There were no
      significant morphologic or histopathologic abnormalities of the liver and kidney
      in the H-S and steel shot groups. Results indicated that mallards dosed orally
      with eight No. 4 H-S pellets were not adversely affected over a 30-day period,
      and that H-S provides another environmentally safe nontoxic shot for use in
      waterfowl hunting.

PMID- 14567227
TI  - Physiologic responses of grizzly bears to different methods of capture.
AB  - The physiologic effects of two methods of capture, chemical immobilization of
      free-ranging (FR) bears by remote injection from a helicopter and physical
      restraint (PR) by leg-hold snare prior to chemical immobilization, were compared
      in 46 grizzly bears (Ursus arctos) handled during 90 captures between 1999 and
      2001. Induction dosages and times were greater for FR bears than PR bears, a
      finding consistent with depletion of, or decreased sensitivity to,
      catecholamines. Free-ranging bears also had higher rectal temperatures 15 min
      following immobilization and temperatures throughout handling that correlated
      positively with induction time. Physically restrained bears had higher white
      blood cell counts, with more neutrophils and fewer lymphocytes and eosinophils,
      than did FR bears. This white blood cell profile was consistent with a stress
      leukogram, possibly affected by elevated levels of serum cortisol. Serum
      concentrations of alanine aminotransferase, aspartate aminotransferase, and
      creatine kinase were higher in PR bears that suggested muscle injury. Serum
      concentrations of sodium and chloride also were higher in PR bears and attributed
      to reduced body water volume through water deprivation and increased insensible
      water loss. Overall, different methods of capture resulted in different patterns
      of physiologic disturbance. Reducing pursuit and drug induction times should help
      to minimize increase in body temperature and alteration of acid-base balance in
      bears immobilized by remote injection. Minimizing restraint time and ensuring
      snare-anchoring cables are short should help to minimize loss of body water and
      prevent serious muscle injury in bears captured by leg-hold snare.

PMID- 14567228
TI  - Anesthesia of polar bears using xylazine-zolazepam-tiletamine or zolazepam
      tiletamine.
AB  - Immobilization features and physiologic effects of combinations of xylazine
      zolazepam-tiletamine (XZT) and zolazepam-tiletamine (ZT or Telazol) were compared
      in nine captive and 17 free-ranging polar bears (Ursus maritimus) between 1998
      and 2001. Although induction time was similar between drugs, induction dosage and
      volume were less with XZT. Induction of immobilization with XZT was predictable
      and smooth, muscle relaxation was good, and all bears remained completely
      immobilized and unresponsive to stimuli throughout a 1 hr handling period. The
      combination XZT was safely tolerated at two to three times the recommended dosage
      of 5 mg/kg (i.e., xylazine at 2 mg/kg + Telazol at 3 mg/kg). Bears immobilized
      with XZT had slower pulse rates, higher mean arterial pressures, and lower
      arterial oxygen tensions than bears immobilized with ZT. Rectal temperature
      increased slowly over time (approximately 0.5 C per hr) following immobilization
      with XZT. Based on response to a painful stimulus (compression of a claw bed),
      XZT was a more effective analgesic than ZT. Although the immobilization effects
      of XZT could not be reversed with the alpha 2-antagonist drug tolazoline, they
      were reversed with yohimbine or atipamezole. However, the time to complete
      reversal of effects (i.e., standing and ambulatory) was highly variable among
      bears.

PMID- 14567229
TI  - Evaluation of three combinations of anesthetics for use in free-ranging alpine
      marmots (Marmota marmota).
AB  - From April 1998 to September 2000, 241 free-ranging alpine marmots (Marmota
      marmota) were anesthetized in the course of a field project using either xylazine
      plus ketamine (XK), medetomidine plus ketamine (MK), or xylazine plus a 1:1
      mixture of zolazepam and tiletamine (XZT). For each of the combinations, the
      respective doses for short term and long-term surgery were established and
      seasonal variations in the amount of drugs needed were assessed. No fatalities
      occurred, and doses for efficient and safe anesthesia in spring were as follows
      (XK, MK, and XZT, respectively, in mg/kg body mass): short term surgery 3 + 40,
      0.25 + 35, and 3 + 15; long term surgery 20 + 80, 0.5 + 70, and 10 + 20. In late
      summer/autumn, higher doses (20 + 60, 0.2 + 60, and 10 + 15 for short term
      surgery) had to be administered, probably due to increase of marmots' body fat
      content. Heart rate, respiratory rate, rectal temperature, palpebral reflex,
      muscle relaxation, and analgesia were monitored to evaluate the animals'
      responses to each of the drug combinations. Hypothermia was induced by all
      combinations and heart rate significantly decreased during anesthesia, especially
      in marmots receiving MK. Respiratory rate was highly variable and no significant
      differences between the drugs were found. Muscle relaxation was rather poor in
      marmots anesthetized with XK. The XZT combination tended to have a longer
      induction period but was found to subsequently depress the palpebral reflex and
      induce muscle relaxation and analgesia very efficiently. We conclude that,
      regardless of the anesthetics used, doses should always be adjusted to the
      planned manipulations, the marmots' nutritional state, and to the time of year.
      Furthermore, close monitoring of physiologic parameters, especially body
      temperature, should be guaranteed. On the basis of physiologic and behavioral
      responses, XZT is the most effective drug combination for anesthetizing alpine
      marmots, especially for long term, potentially painful procedures.

PMID- 14567230
TI  - Immobilization of North American porcupines (Erethizon dorsatum) using ketamine
      and xylazine.
AB  - We performed 345 immobilizations on 150 North American porcupines (Erethizon
      dorsatum) using a mixture of ketamine hydrochloride (KH) and xylazine
      hydrochloride (XH). A subsample of 184 immobilizations performed on 124
      individuals from 4 May to 7 November 2000 and from 22 January to 30 April 2001 is
      thoroughly analyzed. In contrast to published procedures, we found that injecting
      drugs into tail muscles was more efficient than into longitudinal muscles of the
      lower back, because tail injections decreased the need of multiple injections by
      26%. Using tail injections, we were able to reduce the dose by 50% from other
      published reports without significantly affecting induction, immobilization,
      standing, or recovery times. We suggest that injection of 5 mg KH/kg and 2 mg
      XH/kg in the tail as a standard procedure to immobilize North American
      porcupines. Body mass significantly affected the induction and standing times for
      single injections performed in the tail, irrespective of dose or sex. Sex, dose,
      and mass had no effect on the quality of immobilizations and the respiration rate
      of individuals during immobilization. We report a 0.87% mortality rate using a
      mixture of KH and XH and suggest ways to further decrease this rate.

PMID- 14567231
TI  - Helminths of the ocelot from southern Texas.
AB  - In the USA, the ocelot (Leopardus pardalis) is a highly endangered felid found
      only in a few remaining vestiges of native thornshrub brushland in the Lower Rio
      Grande Valley (LRGV) of extreme southern Texas. From 1987-1998, carcasses of 15
      adult ocelots that died of vehicular accidents or natural causes were examined
      for helminths. All cats had 1-8 (mean = 3) helminth species. All were infected
      with 1-101 (mean +/- SE = 32 +/- 7) Toxascaris leonina. Other helminths from
      these ocelots were Alaria marcianae, Brachylaima sp., Mesocestoides lineatus,
      Taenia rileyi, Oncicola canis, Dirofilaria immitis, Physaloptera rara,
      Ancylostoma tubaeformae, Cylicospirura chevreuxi, Vogeloides felis, and
      Metathelazia californica. Additionally, two cats had scarring of the aorta with
      lesions typical of those caused by Spriocerca lupi, although larval nematodes
      were not seen. A clinal variation in size of nearly three orders of magnitude was
      noted in the diplostomatid trematodes in the small intestine of one adult male
      ocelot. Despite the differences in size, all specimens appeared morphologically
      identical and were regarded as A. marcianae. Helminth prevalences and abundances,
      including those of potentially pathogenic species like D. immitis, were low.
      Although a single heartworm infection may have contributed to the death of one
      ocelot, helminth infections in general seemed to be of no great consequence to
      this endangered ocelot population. The helminth fauna of ocelots in the LRGV is
      reflective of that from wild felids in general; all have been reported previously
      from the bobcat (Lynx rufus) and mountain lion (Puma concolor) elsewhere in
      Texas.

PMID- 14567232
TI  - Multicentric T-cell lymphoma associated with feline leukemia virus infection in a
      captive namibian cheetah (Acinonyx jubatus).
AB  - This case report describes a multicentric lymphoma in a 4 yr old female wildborn
      captive cheetah (Acinonyx jubatus) in Namibia after being housed in an enclosure
      adjacent to a feline leukemia virus (FeLV) infected cheetah that had previously
      been in contact with domestic cats. The year prior to the onset of clinical
      signs, the wild-born cheetah was FeLV antigen negative. The cheetah subsequently
      developed lymphoma, was found to be infected with FeLV, and then rapidly
      deteriorated and died. At necropsy, the liver, spleen, lymph nodes, and multiple
      other organs were extensively infiltrated with neoplastic T-lymphocytes. Feline
      leukemia virus DNA was identified in neoplastic lymphocytes from multiple organs
      by polymerase chain reaction and Southern blot analysis. Although the outcome of
      infection in this cheetah resembles that of FeLV infections in domestic cats, the
      transmission across an enclosure fence was unusual and may indicate a heightened
      susceptibility to infection in cheetahs. Caution should be exercised in holding
      and translocating cheetahs where contact could be made with FeLV-infected
      domestic, feral, or wild felids.

PMID- 14567233
TI  - A serologic survey of wild felids from central west Saudi Arabia.
AB  - Forty-five wildcats (Felis silvestris), 17 sand cats (Felis margarita), and 17
      feral domestic cats were captured in central west Saudi Arabia, between May 1998
      and April 2000, with the aim to assess their exposure to feline immunodeficiency
      virus/puma lentivirus (FIV/PLV), feline leukaemia virus (FeLV), feline
      herpesvirus (FHV-1), feline calicivirus (FCV), feline coronavirus (FCoV), and
      feline panleukopenia virus (FPLV). Serologic prevalence in wildcats, sand cats,
      and feral domestic cats were respectively: 6%, 0%, 8% for FIV/PLV; 3%, 8%, 0% for
      FeLV; 5%, 0%, 15% for FHV-1; 25%, 0%, 39% for FCV; 10%, 0%, 0% for FCoV; and 5%,
      0%, 8% for FPLV. We recorded the first case of FeLV antigenemia in a wild sand
      cat. Positive results to FIV/PLV in wildcats and feral cats confirmed the
      occurrence of a feline lentivirus in the sampled population.

PMID- 14567234
TI  - Natural infection of a great egret (Casmerodius albus) with eastern equine
      encephalitis virus.
AB  - In July 2001, a great egret (Casmerodius albus) was found dead in Charlton
      County, Georgia (USA) and submitted to the Southeastern Cooperative Wildlife
      Disease Study (The University of Georgia, Athens, Georgia). Histopathologic
      findings included severe hepatic necrosis and necrosis of sheathed arterioles.
      Eastern equine encephalitis (EEE) virus was isolated from brain and heart using
      Vero cells and was identified using a standard micro-neutralization test and
      reverse transcription polymerase chain reaction (rtPCR). Streptavidin-biotin
      alkaline phosphatase immunohistochemistry using mouse anti-EEE virus monoclonal
      antibody demonstrated EEE antigen within cells of the sheathed arterioles and
      scattered mononuclear cells in the splenic parenchyma. To the authors' knowledge,
      this is the first description of natural infection and pathologic effects of EEE
      virus infection in a great egret.

PMID- 14567235
TI  - Failure to transmit avian vacuolar myelinopathy to mallard ducks.
AB  - Avian vacuolar myelinopathy (AVM) is a neurologic disease that has been diagnosed
      in free-ranging birds in the southeastern United States. Bald eagles (Haliaeetus
      leuocephalus), American coots (Fulica americana), and mallards (Anas
      platyrhynchos) have been affected. Previous investigations have not determined
      the etiology of this disease. In November and December 2002, we attempted to
      induce AVM in game-farmed mallards through four, 7-day exposure trials. Mallards
      were housed in six groups of eight, with two of these groups serving as controls.
      One group was housed with AVM-affected coots; one group was tube fed daily with
      water from the lake where affected coots were captured; one group was tube fed
      daily with aquatic vegetation (Hydrilla verticillata) from the same lake; and
      another group was tube fed daily with sediment from the lake. No ducks exhibited
      clinical neurologic abnormalities consistent with AVM and no evidence of AVM was
      present at histopathologic examination of brain tissue. Although limitations in
      sample size, quantity of individual doses, frequency of dose administration,
      duration of exposure, and timing of these trials restrict the interpretation of
      the findings, AVM was not readily transmitted by direct contact, water, hydrilla,
      or sediment in this investigation.

PMID- 14567236
TI  - A survey of the parasites of coyotes (Canis latrans) in New York based on fecal
      analysis.
AB  - Coyotes (Canis latrans) have colonized northeastern North America only within the
      past 10-80 yr. We examined feces of coyotes in 2000-01 at three sites in New York
      (USA) to survey parasites in the region. Two cestodes, nine nematodes, five
      protozoa, one trematode, and two arthropods were identified from 145 coyote fecal
      samples. Parasite component community diversity was higher (n = 16 species) in
      southern New York than in middle and northern sites (nine species each) and
      infracommunity species richness was greater in southern New York than at the
      other sites. These differences may reflect the variable diets of coyotes, as well
      as recent colonization of the region and the mixing of component communities from
      expanding coyote populations.

PMID- 14567237
TI  - Prevalence of Leptospira and Brucella antibodies in wild boars (Sus scrofa) in
      Tuscany, Italy.
AB  - Five hundred sixty-two blood samples were collected from wild boars (Sus scrofa)
      shot in six districts of Tuscany, central Italy, between 1997 and 2000. Sera were
      examined for antibodies specific for Leptospira interrogans by microagglutination
      test and Brucella spp. by the Rose Bengal test and indirect enzyme-linked
      immunosorbent assay. Thirty-four (6.0%) samples tested positive for anti
      Leptospira antibodies, 29 (5.1%) sera were positive for anti-L. interrogans
      serovar bratislava antibodies (titres ranging from 1:100-1:400), and 5 (0.9%)
      sera were positive for anti-L. interrogans serovar icterohaemorrhagiae antibodies
      (titres 1:100). All the examined sera were negative for anti-Brucella antibodies.

PMID- 14567238
TI  - Biliary adenocarcinoma in a stranded northern elephant seal (Mirounga
      angustirostris).
AB  - A stranded adult female northern elephant seal (Mirounga angustirostris) was
      admitted to a rehabilitation hospital grossly underweight and lethargic in April
      2001. The animal was icteric, had severe bilirubinemia, and elevated serum gamma
      glutamyl transferase concentrations. Laparoscopy under anesthesia revealed
      multiple masses up to 3 cm diameter throughout the liver and spleen and the
      animal was euthanized. Abnormal gross postmortem findings included green serous
      fluid in the abdominal cavity and 0.5 to 3 cm diameter yellow nodules scattered
      throughout the liver, spleen, and lymph nodes. Histopathology revealed a biliary
      adenocarcinoma with metastases to the liver, spleen, lymph nodes, adrenal gland,
      and pancreas. This is believed to be the first reported case of neoplasia in a
      northern elephant seal.

PMID- 14567239
TI  - Chemical immobilization of crested porcupines with tiletamine HCl and zolazepam
      HCl (Zoletil) under field conditions.
AB  - The combination of tiletamine HCl and zolazepam HCl has been used on many species
      of wild mammals. Short induction time, low dosage, satisfactory safety margins,
      relatively constant immobilization time, and smooth recovery are benefits
      reported. This combination (Zoletil 100) was used during a study on behavioural
      ecology of the crested porcupine (Hystrix cristata) in a Mediterranean coastal
      area (Maremma Regional Park, Tuscany, Italy). We used this mixture 42 times on 31
      individuals. Mean adult dose was (+/- SE) 7.24 +/- 0.37 mg/kg (74.0 +/- 3.0
      mg/individual). Average adult induction time was 5.3 min (+/- 1.1) and average
      adult immobilization time was 22.6 min (+/- 6.0). One adult male porcupine died
      after chemical restraints. The use of tiletamine-zolazepam seems adequate for
      chemical immobilization of crested porcupines under field conditions, mainly
      because of its short induction time, small volume to be injected and wide safety
      margin.

PMID- 14567240
TI  - Avian cholera in a southern giant petrel (Macronectes giganteus) from Antarctica.
AB  - A southern giant petrel (Macronectes giganteus) was found dead at Potter
      Peninsula, King George Island, South Shetland, Antarctica. The adult male was
      discovered approximately 48 hr after death. Macroscopic and microscopic lesions
      were compatible with avian cholera and the bacterium Pasteurella multocida subsp.
      gallicida, serotype A1 was isolated from lung, heart, liver, pericardial sac, and
      air sacs. In addition, Escherichia coli was isolated from pericardial sac and air
      sacs. This is the first known report of avian cholera in a southern giant petrel
      in Antarctica.

PMID- 14567241
TI  - Mycobacterium chelonae osteoarthritis in a Kemp's ridley sea turtle (Lepidochelys
      kempii).
AB  - A stranded Kemp's ridley sea turtle (Lepidochelys kempii) was rescued and treated
      at the National Aquarium in Baltimore (Maryland, USA) for inappetence and
      epidermal appendicular and plastral lesions. After 4 mo of care, the turtle
      developed a swollen left elbow joint. Within 1 mo of initial swelling, osteolytic
      lesions developed in the proximal radius and ulna. The elbow joint was surgically
      debrided, flushed, and cultured. The incision dehisced 10 days after surgery.
      Mycobacterium chelonae was cultured from the left elbow joint and from a skin
      nodule of the dorsum of the right front flipper. The turtle was euthanized due to
      apparent systemic infection with M. chelonae. Mycobacterium chelonae was isolated
      from cultures taken at necropsy of the lung, liver, spleen, kidney, and
      pericardium. Osteoarthritic infections with M. chelonae have not been reported in
      reptiles. Additionally, primary osteoarthritic diseases of synovial joints are
      uncommon in reptilian species. Due to the paucity of reports of mycobacterial
      diseases in sea turtles, the continued documentation of these cases will increase
      knowledge and understanding in caring for these endangered animals.

PMID- 14567242
TI  - Use of immunohistochemistry to diagnose chytridiomycosis in dyeing poison dart
      frogs (Dendrobates tinctorius).
AB  - Chytridiomycosis, caused by Batrachochytrium dendrobatidis, is an emerging
      disease of both wild and captive amphibians, posing a threat to their survival in
      many parts of the world. As the disease can be difficult to diagnose on routine
      pathologic sections, the purpose of this study was to develop an additional
      method for visualization. To accomplish this, immunohistochemical staining was
      applied to histologic skin sections from four experimentally infected Dyeing
      poison dart frogs (Dendrobates tinctorius). Staining of the positive tissue
      sections was distinct and readily visualized, making this technique a valuable
      ancillary diagnostic test for this important disease.

PMID- 14567243
TI  - Population monitoring in support of a rabies vaccination program for skunks in
      Arizona.
AB  - Three population monitoring methods were evaluated in support of a
      trap/vaccinate/release program for controlling a bat variant of rabies virus in
      skunks (Mephitis mephitis) in Flagstaff, Arizona (USA). Skunks were the primary
      species targeted for population monitoring during the program, but feral cats
      were also monitored as they represented an abundant secondary vector species
      capable of rabies transmission. Skunks were vaccinated and released, except for a
      subset tested for rabies. All captured cats were placed in the local animal
      shelter. Spotlight surveys essentially did not detect skunks, and were not able
      to detect reductions in the cat population. Catch-per-unit-effort marginally
      tracked population trends, but a passive track index adapted for an urban setting
      was most sensitive for detecting changes in skunk and cat populations. Mark
      recapture population estimates could not be validly calculated from the data on
      captures and recaptures due to multiple violations of analytical assumptions.

PMID- 14567244
TI  - Dental radiography: an overview.

PMID- 14567245
TI  - Viral hepatitis.

PMID- 14567246
TI  - Students rating teachers.

PMID- 14567247
TI  - Cardiac catheterization's side effects.

PMID- 14567248
TI  - In a fog.

PMID- 14567249
TI  - [Frontline of community-acquired pneumonia treatment].

PMID- 14567250
TI  - [Recent findings based on the results of the post-marketing surveillance of
      vancomycin hydrochloride for intravenous infusion].
AB  - Vancomycin Hydrochloride for Intravenous Infusion (VCM) was launched as a
      therapeutic agent for infections caused by Methicillin-Cephem Resistant
      Staphylococcus aureus (MRSA) in October 1991. The results of the post-marketing
      surveillance conducted in accordance with GPMSP for 6 years after the launch are
      as follows. The population studied included 3,037 patients administered this drug
      intravenously at 1,099 institutions across Japan from October 1991 through
      September 1997, and among which, 28 patients were excluded because the follow-up
      was impossible. Consequently, 3,009 patients were included in the safety
      evaluation and 2,827 patients in the efficacy evaluation, excluding 182 patients
      due to the off-label use, etc. The daily dosage of this drug was 40 mg/kg for
      pediatric patients and 1 or 2 g for adult/elderly patients, and the duration of
      treatment was commonly 1-3 weeks. The daily dosage and the duration of treatment
      tended to be decreased over years. The improvement rate by disease was in the 70
      to 79% range for respiratory tract infections such as pneumonia, and 80% or more
      for other diseases such as sepsis and osteomyelitis. With respect to the
      bacteriological efficacy against MRSA, the eradication rate was 66.9%. The number
      of cases with adverse drug reactions including clinical laboratory abnormalities
      was 404 patients (13.43%) and a total of 561 adverse drug reactions were
      reported. Although there was no trend of particularly high frequency of adverse
      drug reactions even among elderly patients. Based on the above, VCM is a highly
      useful drug, which is reliably expected to be effective against MRSA infections,
      and it seems that VCM should be administered promptly to patients in which MRSA
      has been identified as a causative pathogen. For the use of VCM, if the optimum
      dose and mode of administration are selected while taking account of the age and
      renal function, adverse drug reactions can also be reduced.

PMID- 14567251
TI  - [Surveillance on concurrent administration of quinolones and anti-inflammatory
      drugs in a community hospital].
AB  - Since convulsions associated with the concurrent administration of enoxacin and
      fenbufen were reported in 1986, the concurrent administration of quinolones and
      anti-inflammatory drugs has been regulated to be contraindicated or carefully
      administered. However, the real incidence of the co-administration is not clear.
      We surveyed the incidence of co-administration of these drugs from the
      prescriptions in a community hospital. Quinolones were prescribed in 1% of the
      out-patients, and anti-inflammatory drugs were co-administrated in 16% of
      quinolone-prescribed patients. Among quinolones prescribed, levofloxacin was used
      most frequently. And acetaminphen (including acetaminophen-combination) was most
      frequently prescribed with quinolones, and anti-inflammatory drugs, which is
      regulated to be carefully administrated with quinolones, were frequently co
      prescribed. In medical practice, quinolones were revealed to be co-administered
      with anti-inflammatory drugs. Since our recent report suggests that each
      quinolone and each anti-inflammatory drug has different activity in their drug
      interaction, it should be necessary to recognize the interaction of these drugs
      separately for their effective and safe use in clinical field.

PMID- 14567252
TI  - [Clinical efficacy and bacteriological studies of clarithromycin and cefdinir
      against group A beta-hemolytic streptococcal tonsillopharyngitis].
AB  - The clinical efficacy and safety of clarithromycin (CAM) and cefdinir (CFDN) were
      evaluated in 65 pediatric outpatients with group A beta-hemolytic streptococcal
      tonsillopharyngitis. Treatment was "effective" or better in 26 (78.8%) children
      receiving CAM and in 27 (87.1%) receiving CFDN based on antigen clearance and the
      "Criteria for Evaluation in Clinical Trials of Antibacterial Agents in Children"
      proposed by Japan Society of Chemotherapy (p = NS). The causative organisms were
      eradicated in 94.7% and 93.8% of subjects in the CAM and CFDN groups,
      respectively (p = NS). Adverse drug reactions were limited to moderate diarrhea
      in one patient in each group, and subsided during treatment. Causative organisms
      exhibited good susceptibility to CAM and CFDN. These results suggest excellent
      efficacy, safety and usefulness of CAM and CFDN in the treatment of group A beta
      hemolytic streptococcal tonsillopharyngitsis in children.

PMID- 14567253
TI  - [The effect of intravenous ciprofloxacin for community acquired pneumonia in
      adults].
AB  - To verify the indication of intravenous fluoroquinolone in guideline for
      treatment of community-acquired pneumonia published in Japanese Respiratory
      Society, the effect of intravenous ciprofloxacin was investigated in this study.
      49 cases of community-acquired pneumonia were treated by intravenous
      ciprofloxacin. Total response rate was 77.1%. 66.7% of response rate was achieved
      even in the cases which other antibiotics had been already introduced and failed.
      The data of this study indicated that intravenous ciprofloxacin was one of the
      effective and appropriate therapeutics for community-acquired pneumonia in
      adults.

PMID- 14567254
TI  - [Yearly changes in antibacterial activities of cefozopran against various
      clinical isolates between 1996 and 2001--I. Gram-positive bacteria].
AB  - The in vitro antibacterial activities of cefozopran (CZOP), an agent of cephems,
      against various clinical isolates obtained between 1996 and 2001 were yearly
      evaluated and compared with those of other cephems, oxacephems, carbapenems, and
      penicillins. A total of 1,274 strains in 15 species of Gram-positive bacteria
      were isolated from the clinical materials annually collected from January to
      December, and consisted of methicillin-susceptible Staphylococcus aureus (MSSA),
      methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis,
      Staphylococcus haemolyticus, Streptococcus pyogenes, Streptococcus agalactiae,
      Streptococcus pneumoniae, Enterococcus faecalis, Enterococcus faecium,
      Enterococcus avium, and Peptostreptococcus spp. CZOP possessed stable
      antibacterial activities against all strains tested throughout 6 years. The MIC90
      of CZOP against MRSA and S. haemolyticus tended to decrease while against S.
      pneumoniae and Peptostreptococcus spp., tended to increase year by year. However,
      the MIC90 just changed a little and were consistent with the results from the
      studies performed until the new drug application approval. Increases in the MIC90
      against S. pneumoniae were also observed with ceftazidime (CPR), cefepime (CFPM),
      flomoxef (FMOX), sulbactam/cefoperazone (SBT/CPZ), and imipenem (IPM). Increases
      in the MIC90 against Peptostreptococcus spp. were also observed with FMOX,
      SBT/CPZ, and IPM. In conclusion, the annual antibacterial activities of CZOP
      against the Gram-positive bacteria did not considerably change. It, therefore,
      was suggested that CZOP had maintained high antibacterial activity during 6 years
      of post marketing.

PMID- 14567255
TI  - [Yearly changes in antibacterial activities of cefozopran against various
      clinical isolates between 1996 and 2001--II. Gram-negative bacteria].
AB  - The in vitro antibacterial activities of cefozopran (CZOP), an agent of cephems,
      against various clinical isolates obtained between 1996 and 2001 were yearly
      evaluated and compared with those of other cephems, oxacephems and carbapenems. A
      total of 3,245 strains in 32 species of Gram-negative bacteria were isolated from
      the clinical materials annually collected from January to December, and consisted
      of Moraxella subgenus Branhamella catarrhalis, Escherichia coli, Citrobacter
      freundii, Citrobacter koseri, Klebsiella pneumoniae, Klebsiella oxytoca,
      Enterobacter aerogenes, Enterobacter cloacae, Serratia marcescens, Proteus
      mirabillis, Proteus vulgaris, Morganella morganii, Providencia spp. (P.
      alcalifaciens, P. rettgeri, P. stuartii), Pseudomonas aeruginosa, Pseudomonas
      putida, Burkholderia cepacia, Stenotrophomonas maltophilia, Haemophilus
      influenzae, Acinetobactor baumannii, Acinetobactor lwoffii, Bacteroides fragilis
      group (B. fragilis, B. vulgatus, B. distasonis, B. ovatus, B. thetaiotaomicron),
      and Prevotella spp. (P. melaninogenica, P. intermedia, P. bivia, P. oralis, P.
      denticola). CZOP possessed stable antibacterial activities against M. (B.)
      catarrhalis, E. coli, C. freundii, C. koseri, K. pneumoniae, K. oxytoca, E.
      aerogenes, E. cloacae, S. marcescens, P. mirabilis, P. vulgaris, M. morganii,
      Providencia spp., P. aeruginosa, and A. lwoffii throughout 6 years. The MIC90 of
      CZOP against those strains were consistent with those obtained from the studies
      performed until the new drug application approval. On the other hand, the MIC90
      of CZOP against H. influenzae yearly obviously increased with approximately 64
      time difference during the study period. The MIC90 of cefpirome, cefepime, and
      flomoxef against H. influenzae also yearly tended to rise. The present results
      demonstrated that CZOP had maintained the antibacterial activity against almost
      Gram-negative strains tested. However, the decrease in antibacterial activities
      of CZOP against B. cepacia, and H. influenzae was suggested.

PMID- 14567256
TI  - [Synthesis of architectural complex natural products, potent, antibacterial and
      anticancer activity].

PMID- 14567257
TI  - [Application of real-time polymerase chain reaction technology to detect
      prostatic bacteria in patients with chronic prostatitis/chronic pelvic pain
      syndrome].

PMID- 14567258
TI  - [The effect of antibiotics and bismuth on sulfate-reducing bacteria].

PMID- 14567259
TI  - Does full disclosure of medical errors affect malpractice liability? The jury is
      still out.
AB  - BACKGROUND: Mandatory disclosure of medical errors has been advocated to improve
      patient safety. Many resist mandatory disclosure policies because of concerns
      about increasing malpractice exposure. It has been countered that malpractice
      liability actually decreases when there is full disclosure of medical errors. A
      comprehensive literature search was conducted to determine what is known about
      the impact of full disclosure on malpractice liability. METHODS: Electronic
      searches of multiple databases were supplemented with hand searches of
      bibliographies and communication with recognized experts in the field. RESULTS:
      Screening the titles, abstracts, and, in many cases, the full articles from more
      than an estimated 5,200 citations resulted in identification of one published
      study directly examining malpractice liability when a policy of full disclosure
      was implemented. DISCUSSION: Despite extensive literature on the impact of
      disclosure on malpractice liability, few well-designed studies have focused on
      the real-world impact on the volume and cost of suits following implementation of
      a full disclosure policy. Many articles examine why patients sue their doctors,
      suggesting that some lawsuits may be averted by disclosure, but the articles do
      not allow us to estimate the additional suits that would be created by
      disclosure. Additional studies addressing the effect of disclosure on malpractice
      liability are needed.

PMID- 14567260
TI  - Microsystems in health care: Part 8. Developing people and improving work life:
      what front-line staff told us.
AB  - BACKGROUND: The articles in the Microsystems in Health Care series have focused
      on the success characteristics of high-performing clinical microsystems.
      Realization is growing about the importance of attracting, selecting, developing,
      and engaging staff. By optimizing the work of all staff members and by promoting
      a culture where everyone matters, the microsystem can attain levels of
      performance not previously experienced. CASE STUDY: At Massachusetts General
      Hospital Downtown Associates (Boston), a primary care practice, the human
      resource processes are specified and predictable, from a candidate's initial
      contact through each staff member's orientation, performance management, and
      professional development. Early on, the new employee receives materials about the
      practice, including a practice overview, his or her typical responsibilities, the
      performance evaluation program, and continuous quality improvement. Ongoing
      training and education are supported with skill labs, special education nights,
      and cross-training. The performance evaluation program, used to evaluate the
      performance of all employees, is completed during the 90-day orientation and
      training, quarterly for one year, and annually. CONCLUSION: Some health care
      settings enjoy high morale, high quality, and high productivity, but all too
      often this is not the case. The case study offers an example of a microsystem
      that has motivated its staff and created a positive and dynamic workplace.

PMID- 14567261
TI  - Learning to leverage existing information systems: Part 1. Principles.
AB  - BACKGROUND: The success of performance improvement efforts depends on effective
      measurement and feedback regarding clinical processes and outcomes. Yet most
      health care organizations have fragmented rather than integrated data systems.
      Methods and practical guidance are provided for leveraging available information
      sources to obtain and create valid performance improvement-related information
      for use by clinicians and administrators. CASE VIGNETTE: At Virginia Mason Health
      System (VMHS; Seattle), a vertically integrated hospital and multispecialty group
      practice, patient records are paper based and are supplemented with electronic
      reporting for laboratory and radiology services. Despite growth in the resources
      and interest devoted to organization-wide performance measurement, quality
      improvement, and evidence-based tools, VMHS's information systems consist of
      largely stand-alone, legacy systems organized around the ability to retrieve
      information on patients, one at a time. By 2002, without any investment in
      technology, VMHS had developed standardized, clinic-wide key indicators of
      performance updated and reported regularly at the patient, provider, site, and
      organizational levels. LEVERAGING EXISTING SYSTEMS: On the basis of VHMS's
      experience, principles can be suggested to guide other organizations to explore
      solutions using their own information systems: for example, start simply, but
      start; identify information needs; tap multiple data streams; and improve
      incrementally.

PMID- 14567262
TI  - Learning to leverage existing information systems: Part 2. Case studies.
AB  - BACKGROUND: The ability to use available administrative and clinical information
      to produce performance reports is a key element of quality improvement. Six
      health care systems were identified that have done a particularly effective or
      innovative job of creating and implementing performance measurement tools and
      systems by using data available in existing clinical and administrative
      information systems: Dean Health System (Madison, WI), Sharp HealthCare (San
      Diego), Henry Ford Health System (Detroit), Scripps Health (San Diego), Legacy
      Health System (Portland, OR), and Lovelace Health System (Albuquerque). SUMMARY
      THOUGHTS: Interest in comparative performance information for health care
      organizations remains strong. The perfect measure set has not yet been invented.
      Every measure has one or more flaws, as do the data systems available to support
      them. Managers may take comfort, however, in the knowledge that performance
      measures need not be perfect to be useful. Measures tend to improve when people
      use the data to inform decisions that matter. Even the most accurate data,
      though, are not useful if there is either too much or too little "organizational
      distance" between the unit of analysis for the data and the unit of control for
      making change. Some systems have adopted a layered approach to performance
      measurement, in which measures are aggregated for reporting and use at the level
      of major operating units or divisions and then disaggregated for reporting and
      use at smaller levels and eventually to the level of individual clinicians.

PMID- 14567263
TI  - Using "get with the guidelines" to improve cardiovascular secondary prevention.
AB  - BACKGROUND: "Get With The Guidelines (GWTG)" was developed and piloted by the
      American Heart Association (AHA), New England Affiliate; MassPRO, Inc.; and other
      organizations to reduce the gap in the application of secondary prevention
      guidelines in hospitalized cardiovascular disease patients. Collaborative
      learning programs and technology solutions were created for the project. THE
      PATIENT MANAGEMENT TOOL (PMT): The interactive Web-based patient management tool
      (PMT) was developed using quality measures derived from the AHA/American College
      of Cardiology secondary prevention guidelines. It provided data entry, embedded
      reminders and guideline summaries, and online reports of quality measure
      performance, including comparisons with the aggregate performance of all
      hospitals. LEARNING SESSIONS: Multidisciplinary teams from 24 hospitals
      participated in the 2000-2001 pilot. Four collaborative learning sessions and
      monthly conference calls supported team interaction. Best-practices sharing and
      the use of an Internet tool enabled hospitals to change systems and collect data
      on 1,738 patients. SUMMARY AND CONCLUSIONS: The GWTG program, a template of
      learning sessions with didactic presentations, best-practices sharing, and
      collaborative multidisciplinary team meetings supported by the Internet-based
      data collection and reporting system, can be extended to multiple regions without
      requiring additional development. Following the completion of the pilot, the AHA
      adopted GWTG as a national program.

PMID- 14567265
TI  - All outcomes should be disclosed.

PMID- 14567264
TI  - Unanticipated harm to patients: deciding when to disclose outcomes.
AB  - BACKGROUND: Patient safety standards of the Joint Commission on Accreditation of
      Healthcare Organizations require that "patients and, when appropriate, their
      families are informed about the outcomes of care, including unanticipated
      outcomes." WHAT OUTCOMES SHOULD TRIGGER DISCLOSURE: Given that all medical
      treatments have an array of possible outcomes, how do we confidently say that an
      outcome is unanticipated? It is proposed that an adverse outcome meet one of two
      criteria to be considered unanticipated: (1) It would not be included in a
      reasonable informed consent process for treatment of the patient's condition(s)
      and/or would not be expected during the usual course of treatment; and (2) it may
      have been caused by human or systemic error--that is, it is not immediately
      possible to clearly and decisively rule out error. This definition requires less
      judgment because it represents an extension of the existing norms of
      communication that are expressed through the process of informed consent. The
      norms of the informed consent process require that the patient be given all
      pertinent information needed to participate in future treatment decision making.
      CONCLUSIONS AND RECOMMENDATIONS FOR ORGANIZATIONAL POLICIES: Institutional
      policies and procedures should provide a clear approach to the identification,
      reporting, and discussion of unanticipated adverse outcomes, whether or not they
      are associated with error, as well as guidance and an educational program to help
      physicians, staff, and students disclose unanticipated adverse events and error
      in the most appropriate manner.

PMID- 14567266
TI  - Practical techniques and perspectives for the cardiovascular administrator. 
      Ambition drives action.

PMID- 14567267
TI  - The power of purple.
AB  - A brand is a promise. It sets a tone and expectation for patients that are
      negotiating an often-over-whelming health care setting. Enhancing your brand
      identity, when done successfully, will ultimately create an emotional bond to the
      care you are providing. People like brands, and want to believe in something
      special. Incorporating color into your branding strategy can foster an emotional
      impact upon your patients, one patient at a time.

PMID- 14567268
TI  - Using performance improvement strategies to reduce and prevent medication errors.
      1.
AB  - The headlines feature tragic stories describing errors in medical practice.
      Medical literature reveals that errors in medical practice are common. In 1999,
      the Institute of Medicine released its report. "To Err is Human," that detailed
      an estimated 44,000 to 98,000 deaths annually due to medical errors. In September
      of 2002, the Archives of Internal Medicine released a study of medication errors
      observed in 36 healthcare facilities. Medication errors were commonly occurring
      in 19% or nearly one error out of every five doses administered in a typical
      hospital. It is imperative to analyze patient safety issues related to medication
      administration. This paper presents methods to improve the quality of care
      delivered by: Building effective structures through efficient use of technology.
      Establishing improved process through collaboration and team-work. Measuring and
      reporting performance outcomes. Using Performance improvement Strategies to
      Reduce and Prevent Medication Errors.

PMID- 14567269
TI  - Designs that make a difference: the Cardiac Universal Bed model.
AB  - Information contained in this article includes some of the findings from a joint
      research project conducted by Corazon Consulting and Ohio State University
      Medical Center on national trends in Cardiac Universal Bed (CUB) utilization.
      This article outlines current findings and "best practice" standards related to
      the benefits of developing care delivery models to differentiate an organization
      with a competitive advantage in the highly dynamic marketplace of cardiovascular
      care. (OSUMC, a Corazon client, is incorporating the CUB into their Ross Heart
      Hospital slated to open this spring.)

PMID- 14567270
TI  - Cardiac PACS: strategies for planning, integration & vendor selection.
AB  - Cardiologists are clamoring for better imaging techniques, the ability to view
      images from their office or home, and for the resulting improvement in efficiency
      which translates into increased profitability. The future is here; are you ready?
      Cardiac systems have developed into full-blown information management and digital
      imaging systems. Hospitals are moving aggressively to update their cardiac
      information systems and identifying the significant role the CIS (cardiac
      information system) plays in the selection process. It is important to plan the
      infrastructure of your cardiac PACS (picture archival communication system) and
      determine how it will integrate with the radiology PACS. Equally important is the
      integration potential with other hospital information systems such as the
      laboratory, pharmacy and billing, etc. Answers to these decision factors are
      provided in addition to information pertaining to the overall cardiac PACS
      planning process and vendor offerings.

PMID- 14567271
TI  - The crisis confronting Medicaid.

PMID- 14567272
TI  - Health centers and the states. Partnership potential to address the fiscal
      crisis.
AB  - The 38-year-old federal Health Centers program funds community-owned preventive
      and primary health care for 14 million people, mostly from low-income and
      minority groups. Studies show that health centers provide quality health care
      efficiently and effectively. President Bush has begun a major program expansion
      to serve 6 million more people, but the states' fiscal crisis has forced funding
      cutbacks that could undermine the administration's initiative. The authors argue
      that states could actually save money by increasing their investment in health
      centers, given the health centers' record of reducing the need for high-cost
      specialty and hospital care and eliminating health disparities.

PMID- 14567273
TI  - Medicaid's role in ambulatory health care.
AB  - Medicaid plays an enormously important role in ambulatory care financing, both
      primary and specialized, for patients with routine health needs, as well as
      individuals with chronic illness and disability. Nearly all Medicaid
      beneficiaries receive the vast bulk of their health care in ambulatory settings.
      Medicaid plays a critical role for low-income persons, including children,
      pregnant women and families, and elderly and disabled Medicare beneficiaries. The
      Bush administration's proposal to subject federal Medicaid spending to annual
      aggregate limits could be expected to have especially severe effects on states'
      capacity to support ambulatory services and achieve innovations in community
      based care.

PMID- 14567274
TI  - The policy and political context of defending Medicaid.
AB  - Medicaid is often accused of devouring state budgets. In reality, it is a sharp
      decline in revenue that has precipitated the current state fiscal crisis, not the
      growth of health care spending. Nonetheless, in a climate of scarce resources,
      proponents of maintaining health coverage for low-income people through the
      Medicaid program face a complex challenge that requires them to think
      simultaneously about policy and building a political constituency for health care
      for the poor. At the same time, they must challenge the conventional wisdom that
      argues against raising taxes in times of economic weakness.

PMID- 14567275
TI  - Sociological context of TennCare. A public health perspective.
AB  - In the mid-1990s TennCare replaced Medicaid in Tennessee and extended health
      coverage to uninsured and uninsurable adults and children. Throughout its short
      history many management and financial problems have plagued it. In spite of this,
      Tennessee currently provides health coverage to more persons compared to most
      states. It is clear that managed care for the poor was not designed to provide
      disease management; it was designed to provide cost management. Many tangible and
      intangible factors affect an individual's ability to access health care or to
      engage in behavioral practices that promote health and prevent disease. Being of
      low-income and minority status have been historically associated with barriers,
      including obtaining or accessing health care, making lifestyle changes to prevent
      poor health, or complying with medical treatment. This article provides the
      public health perspective of a hypothetical model that extends the managed care
      model to one of health management for the poor and underserved.

PMID- 14567276
TI  - Will using evidence-based approaches to a standards development process improve
      Medicaid policy making? Report on a promising effort.
AB  - In theory, evidence-based medical necessity policy in health care utilization
      review may make resource allocation more equitable. Costs can be managed through
      the consistent application of standards for approval of only those services
      deemed medically necessary and by controlling denials and appeals litigation.
      Additional cost savings may be realized with more efficient utilization review
      processes and concentration on review standards for the specific items or
      services that have the greatest financial impact on overall utilization dollars.
      This article describes a five-step process for evidence-based medical necessity
      standards development and includes illustrative examples from a state Medicaid
      agency project. While early results are promising, data are scarce. The authors,
      nevertheless, believe the approach may prove to be useful on promoting the
      application of evidence-based decision making.

PMID- 14567277
TI  - Trends in physician participation in Medicaid. The California experience.
AB  - Physician participation rates in Medicaid vary widely across the country, and,
      overall, there has been a decline in recent years. We performed an evaluation in
      California of whether the expansion of Medicaid managed care and a physician
      payment increase were associated with an increase over time in the percentage of
      physicians caring for Medicaid patients. Surveys performed before and after these
      strategies were used did not reveal an increase over time in physicians'
      participation in California's Medicaid program. Budgetary constraints will force
      policy makers to confront the priorities of the Medicaid program, to question the
      policy objectives for physician participation in Medicaid, and to consider more
      far-reaching reforms in Medicaid and the overall health care system.

PMID- 14567278
TI  - Can the Veterans Affairs health care system continue to care for the poor and
      vulnerable?
AB  - Can the Veterans Affairs (VA) health care system, long an important part of the
      safety net for disabled and poor veterans, survive the loss of World War II
      veterans--once its largest constituency and still its most important advocates? A
      recent shift in emphasis from acute hospital-based care to care of chronic
      illness in outpatient settings, as well as changes in eligibility allowing many
      more nonpoor and nondisabled veterans into the VA system, will be key
      determinants of long-term survivability. Although allowing less needy veterans
      into the system runs the risk of diluting services to those most in need, the
      long-run effect may be to increase support among a larger and younger group of
      veterans, thereby enhancing political clout and ensuring survivability. It may be
      that the best way to maintain the safety net for veterans is to continue to cast
      it more widely.

PMID- 14567279
TI  - The worsening Medicaid fiscal crisis. Implications for hospitals.
AB  - Medicaid, the nation's health care safety net, has come under increasing pressure
      as most state governments face a fiscal crisis. Cutbacks in funding that decrease
      already inadequate reimbursement, the tightening of eligibility, and a reduction
      of benefits will lead to an increase in the under- and uninsured, further
      straining the ability of hospitals to remain solvent and provide care to this
      vulnerable population. The federal government must increase funding to the
      Medicaid program and the Medicaid hospital disproportionate share while state
      governments must continue a level of funding that will not cause a loss of
      federal matching funds. Both state and federal governments must be held
      accountable for providing the necessary financial support to providers through
      the Medicaid program so that they can continue to serve their nearly 51 million
      poor, disabled, and elderly patients.

PMID- 14567280
TI  - Commonwealth Care Alliance. A new approach to coordinated care for the
      chronically ill and frail elderly that organizationally integrates consumer
      involvement.
AB  - While medical care is becoming more effective, our health care system is becoming
      increasingly fragmented from both a care and a financing perspective. This
      article summarizes our experience with integrating the delivery of care for
      catastrophically ill and frail elderly. We argue that true integration can only
      be done within a framework of a financing mechanism that gives all providers the
      financial incentive to deliver integrated care. Under such a financial
      arrangement, nurse practitioners and social workers provide much of the care
      within the home environment. This results in a higher quality care delivery
      system within a limited budget.

PMID- 14567281
TI  - Hampshire HealthConnect. A local effort increases access to health care for the
      uninsured.
AB  - In the absence of universal coverage, there is a need to develop solutions at a
      local and state level to the dramatic rise in the uninsured. This article
      summarizes a local countywide effort to address this issue in a rural area. Key
      ingredients for success include both hospital leadership (they have significant
      resources at their disposal), extensive community involvement (to maintain
      momentum for the program), and local physician leadership (physicians are, in
      essence, forgoing income in return for a formalization of who is eligible for the
      free care program).

PMID- 14567282
TI  - The history of PediPlace.
AB  - Texas has one of the highest rates of uninsured in the United States. In
      addition, the Medicaid program is one of the poorest programs, in terms of
      benefits, of any state in the union. This article summarizes how a large
      pediatric practice responded to this crisis in a large metropolitan area. Key
      ingredients for success include both physician practice leadership (they have
      significant resources at their disposal), extensive community involvement (to
      provide, in particular, monies for the program), and local hospital involvement
      (for emergency and inpatient services).

PMID- 14567283
TI  - The clouded future of Medicaid.
AB  - Medicaid has become the nation's most important health coverage program, covering
      more individuals and costing more than Medicare. Because Medicaid finances the
      health care for society's most challenging cases, it deserves the
      characterization: "the workhorse of the U.S. health care system." A chief
      difficulty is that the program is housed within state governments, which means
      its fiscal fate is tied to the well-being of state economies. State revenues tend
      to decline just when health care spending and Medicaid spending reach their
      highest points. States have numerous strategies they employ to reduce the rate of
      growth in Medicaid spending, though none have strategies to halt relentless cost
      pressures. The policy challenge today is to survive this difficult period with
      the least damage to vulnerable individuals, families, and safety net providers.

PMID- 14567284
TI  - Universal health coverage in the United Kingdom.
AB  - This United Kingdom has had universal health coverage since 1948, provided
      through its government-funded National Health Service (NHS). In recent years,
      increasing workload and treatment costs have put a considerable strain on the
      NHS. The government has responded to these challenges through a controversial
      program of organizational changes in the NHS. In its most recent policy
      initiatives, the government proposes to increase the proportion of national
      income spent on the NHS and make much greater use of private-sector health care
      providers.

PMID- 14567285
TI  - Health coverage in Italy.
AB  - Italy, as other developed European countries, has a national health service (NHS)
      that, in principle, offers universal health care and coverage to Italians and
      other legal (non-Italian) residents who have full access to health care. Although
      Italy has always spent less for health care than other European countries (Italy,
      in 2002, spent about 8% of its gross national product for health care, which is
      approximately half the level of spending in the U.S.), the government's lack of
      control over spending remained the most relevant problem. To enhance the
      capability to control and monitor the system, mainly in terms of expenditures and
      costs, from the late 1990s to the present, new health reforms were introduced.
      These reforms were in the context of a wider change involving other politics and
      administrative aspects, with a strong push to decentralize the decisions and the
      accountability at the regional level. Now, each region has an individual Health
      Regional Fund allocated for health care, along with the subsequent need to
      implement regional and individualized strategies to assure the governance of the
      cost and quality of care. The National Department of Health now is solely
      responsible to control and monitor the delivery of the essential level of care at
      the regional level, and they have maintained the governance of the drug policy.
      Although the changes synthesized above will require a long period to be fully
      implemented, a few negative effects have already occurred. Nevertheless, all
      citizens in Italy will have full access to any level of care, without any
      restrictions, for complex and costly procedures (as no explicit selection/adverse
      criteria were implemented), and the current policy on drugs does not imply any
      barriers for people (as essential drugs are directly and fully reimbursed by the
      NHS, with a small copayment being the only intervention that may be occasionally
      implemented when considered necessary).

PMID- 14567286
TI  - The impact of detention on the health of asylum seekers.
AB  - Asylum seekers arriving in the United States are often imprisoned for months or
      years while their asylum claims are processed. Recently, Physicians for Human
      Rights and the Bellevue/New York University Program for Survivors of Torture
      released the findings of the first systematic study examining the health of
      detained asylum seekers. The study found that the mental health of asylum seekers
      interviewed was extremely poor, including high levels of symptoms for anxiety,
      depression, and posttraumatic stress disorder, which worsened the longer
      individuals were in detention. The study also raises concerns about the manner in
      which asylum seekers are treated upon arrival in the United States and then while
      in detention. These findings support assertions that detention has a harmful
      effect on the health and well-being of asylum seekers. Policies regarding the
      long-term detention of asylum seekers should be reconsidered.

PMID- 14567287
TI  - Low-dose total body irradiation augments the therapeutic effect of interleukin-2
      in a mouse model for metastatic malignant melanoma.
AB  - BACKGROUND: Low-dose total body irradiation (LTBI) is known for its antitumor
      immune modulatory effects. Moreover, there is theoretical ground suggesting that
      combining LTBI with interleukin-2 (IL-2) will have a synergistic immune-mediated
      antitumor effect. However, the use of LTBI in combination with IL-2 or other
      forms of immunotherapy has not been tested before. AIM OF THE WORK: To test the
      efficacy of combining LTBI and IL-2 in controlling lung metastases in a murine
      model for malignant melanoma compared to IL-2 alone. MATERIAL AND METHODS: Ten
      week-old female C57BL/6 mice were inoculated intravenously (on day 0) with 1
      million B16F1 malignant melanoma cells. The mice received either no treatment
      (control group), LTBI alone (single fraction of 0.75 Gy), IL-2 treatment alone
      (30,000 CU x 2 daily for 5 consecutive days), or a combination of LTBI and IL-2.
      LTBI was given on day +7 and IL-2 treatment started day +8. On day +14, the mice
      were sacrificed and the lungs were removed and analyzed for tumor burden. Lung
      sections were also tested for tumor-infiltrating cells using immunohistochemical
      staining. Peripheral blood and splenic cells were collected and tested for the
      percentage of the various lymphocytic subsets using immunostaining and flow
      cytometry. RESULTS: Tumor burden expressed as the percentage of lung area
      occupied with metastases (+/- 1 SD), was the same in the control group (8.1 +/-
      4.9%), and in the group receiving LTBI alone (8.3 +/- 4.5%). Tumor burden was
      reduced to 6.4% (+/- 3.4%) in the IL-2 alone group (P = 0.3) and further reduced
      to 3% (+/- 1%) in the combined treatment group (P = 0.004). The difference in
      tumor burden between the IL-2 alone group and the combined treatment group was
      statistically significant (P = 0.006). The combined treatment caused a
      significant increase in the number of natural killer (NK) cells and macrophages
      infiltrating the metastatic sites. This was associated with a significant
      increase in the percentage of CD122+ (IL-2R beta) cells and NK cells in both
      peripheral blood and spleens. CONCLUSION: We conclude that combining LTBI and IL
      2 treatment is synergistic and therapeutically more effective than IL-2 alone.
      The data points to NK cells and macrophages as likely major effectors of the
      synergistic outcome of the combined treatment. This observation may have
      important clinical implications in the treatment of patients with metastatic
      malignant melanoma.

PMID- 14567288
TI  - Effects of amitriptyline and fluoxetine upon the in vitro proliferation of tumor
      cell lines.
AB  - Previous publications have suggested that commonly prescribed antidepressants
      have the potential to stimulate the proliferation of extant tumors in human and
      rodent in vivo and in vitro models. The direct effects of amitriptyline and
      fluoxetine were evaluated in assays that detect different aspects of
      proliferative responses at pharmacologically relevant drug concentrations. Three
      in vitro assays of cellular proliferation and clonal growth were used with human
      (MCF7, PA-1 and LS174T) and murine (B16.f10, C-3 and B16.f1) tumor cell lines.
      The cells were exposed to amitriptyline or fluoxetine (0.001-100 microM) for
      different time periods (1-7 days) and at varying serum concentrations (0.1-15%).
      Amitriptyline and fluoxetine failed to significantly stimulate tumor cell
      proliferation, DNA synthesis, or colony formation. Both drugs inhibited B16.f10
      colony growth at concentrations above 5 microM along with significant suppression
      of DNA synthesis in B16.f10 and C-3 cells at 30 microM. Although there were
      generally no effects on cell proliferation by the drugs in the microtiter
      tetrazolium assay, several rare instances of stimulation were noted.
      Amitriptyline and fluoxetine were consistent in their lack of effect or
      inhibition with the human or murine tumor cell lines in conventional in vitro
      assays of cell proliferation and clonogenicity in optimal or suboptimal culture
      conditions.

PMID- 14567289
TI  - Effects of etherlipid analogs on cell membrane functions.
AB  - Hexadecylphosphocholine and other etherlipid-derived substances show a pronounced
      antiproliferative activity on neoplastic cells and a broad spectrum of other
      biological effects on many cell types in vitro and in vivo. Though the precise
      molecular mechanism by which these etherlipid analogs act still remains
      unresolved, it seems clear that it most probably involves some essential function
      of the cell membrane. We investigated the effect of different etherlipids with
      and without cytotoxic activity in etherlipid-susceptible and -resistant tumor
      cell lines on three important membrane functions. We observed various inhibitory
      activities on endocytosis and the uptake of small precursor molecules as sugars,
      amino acids, and alcohols by toxic and nontoxic substances in resistant as well
      as susceptible cells. There was no correlation between the antiproliferative
      characteristics of the compounds and the effects on these membrane transport
      functions. Furthermore, the substances reduced the number of membrane tumor
      necrosis factor-alpha receptors regardless of their antiproliferative properties.
      The results of these investigations suggest that etherlipid analogs may interfere
      with many membrane functions in an unspecific manner. Therefore, many of the
      previously reported biological effects of etherlipids have to be viewed under a
      different light. Future investigation on these compounds should always contain
      appropriate control substances and cell models to really prove the specificity of
      the observed effects.

PMID- 14567290
TI  - siRNA agents inhibit oncogene expression and attenuate human tumor cell growth.
AB  - Cancer is a genomic functional disease with features of oncogene activation and
      tumor suppressor inactivation. These genomic features have resulted in the
      limited effectiveness of conventional therapies and therefore forced considerable
      efforts to explore new types of anticancer agents. It has been clear that
      chemically synthesized or in vivo-expressed short interfering RNA (siRNA) can
      specifically and effectively direct homology-dependent post-transcriptional gene
      silencing. In the present study, we intended to investigate whether siRNA could
      suppress the proliferation of human cancer cells through interfering oncogene
      activities and recovering the functions of tumor-suppressor gene. Single siRNA or
      combinatorial siRNAs were successfully transfected into HeLa cells, lung
      adenocarcinoma cells, hepatoma cells, ovarian carcinoma cells, and melanoma cells
      with cationic lipid complexes. These siRNA molecules not only specifically
      knocked down their cognate targets such as bcl-2, cdk-2, mdm-2, pkc-alpha, tgf
      beta1, H-ras, vegf, and GFP mRNAs, but also effectively suppressed the
      proliferation of cancer cells to different extents. These data suggest that (1)
      all these human cancer cells preserve RNAi machinery; (2) chemically synthesized
      and vector-driven siRNAs can be incorporated into intrinsic RNAi system for
      silencing target mRNA molecules; and (3) the combination of different siRNAs
      inhibits the growth and proliferation of cancer cells.

PMID- 14567292
TI  - [Mitral valve replacement with a bileaflet prosthesis: results of 112 cases].
AB  - We report 112 cases of mitral valvular replacement with bileaflet prothesis. The
      mean age is 40 ans +/- 3.4 years (9-74 years). 71 (65%) are men and 45 (35%) are
      women, the main ethiology of mitral disease is rheumatic fever (94.74%). The
      Saint Jude prothesis is implanted in 70.4% cases. The early post operator
      mortality is 1.8% it is related on low cardiac output. With a mean follow-up of
      110 months, the late mortality is 5.5%. The survey is 97% at 5 years and 94% at
      10 years. The rates of thromboembolic and hemorrhagic complications are 6.3% and
      9%. We report only one case of infective endocarditis. The rate of reintervention
      is 5%. By echocardiography the hemodynamic profile of bileaflet prothesis is
      excellent even with the small size.

PMID- 14567291
TI  - Subcutaneous interleukin-2 in combination with medroxyprogesterone acetate and
      antioxidants in advanced cancer responders to previous chemotherapy: phase II
      study evaluating clinical, quality of life, and laboratory parameters.
AB  - We carried out an open, non-randomized phase II study including all patients
      treated with whatever chemotherapy or combined modality regimen for whatever
      cancer who were in clinical objective response (complete response, CR, or partial
      response, PR) or stable disease (SD). The treatment consisted of administration
      of recombinant interleukin-2 (rIL-2) at a dose of 1.8 MIU subcutaneously three
      times/week (every other day) for the first 2 weeks of every month plus
      medroxyprogesterone acetate (MPA) 500 mg/day every other day plus antioxidant
      agents alpha-lipoic acid 300 mg/day and N-acetyl cysteine 1800 mg/day or
      carbocysteine lysine salt oral solution 2.7 g/day. The treatment was administered
      for 1 year except when progression of disease occurred. The primary study
      endpoints were to define clinical outcome, i.e. duration of response, survival
      (overall survival, OS and progression-free survival, PFS), the toxicity profile,
      and the evaluation of quality of life (QL). As secondary endpoints, we measured
      the changes of lymphocyte count, serum levels of proinflammatory cytokines, IL-2,
      C-reactive protein (CRP) and leptin, blood levels of reactive oxygen species
      (ROS) and antioxidant enzymes (glutathione peroxidase, GPx and superoxide
      dismertase, SOD). From July 1998 to June 2003, 42 patients were enrolled in the
      study (M/F ratio, 39/3; mean age, 62.5 years). Twenty (47.6%) patients were
      elderly (> 65 years). The majority of patients had either head and neck cancer or
      lung cancer, 88% had locally advanced or metastatic disease at diagnosis, and 76%
      had ECOG 0. Forty patients were previously treated with chemotherapy (27 also
      with radiotherapy), two with IL-2 and interfiron (IFN), one with endocrine
      therapy and one with only surgery. We obtained an objective response to
      maintenance treatment of 50%. Median duration of response was 19 months and
      median PFS was 33 months. Median duration of maintenance treatment was 12 months,
      median follow-up duration from diagnosis to June 2003 was 40 months, and median
      follow-up duration from study entry to June 2003 was 17 months. The median
      overall survival has not been reached. Toxicity was negligible. As for QL, a
      significant improvement of cognitive functions was observed, whereas all other
      functioning and symptom scales did not change significantly. As for laboratory
      parameters, absolute lymphocyte count increased significantly, IL-6, IL-1 beta,
      tumor necrosis factor-alpha, CRP, and fibrinogen decreased significantly whereas
      IL-2 and leptin increased significantly after treatment. ROS decreased
      significantly, whereas GPx increased significantly after treatment. Patients
      alive at study end showed a significant increase in absolute lymphocyte count, IL
      2, leptin, and GPx and a significant decrease of proinflammatory cytokines, CRP,
      fibrinogen, and ROS, whereas patients who died before study end exhibited only a
      significant increase in absolute lymphocyte count, IL-2, and GPx and a
      significant decrease of ROS. Long-term combined maintenance therapy with rIL-2 +
      MPA + antioxidant agents is feasible, has a very low toxicity, and results in the
      improvement of clinical outcome, QL, and laboratory parameters.

PMID- 14567293
TI  - [Ulcerations and their classification by Ismael Jorjani].
AB  - Ismael Jorjanio (d. 1137), the Persian physician and philosopher, received his
      medical training in the most famous schools of the Iranian province of khawarizm.
      He wrote several works in which he dealt with medicine and the natural sciences.
      We are interested in the work dealing with the classification of ulcerations as
      proposed by Ismael Jorjani in function with their clinical characteristics and
      evolution as well as with their technical aspects.

PMID- 14567295
TI  - Regarding "Cerebral hyperperfusion syndrome after carotid endarterectomy:
      predictive factors and hemodynamic changes".

PMID- 14567294
TI  - [Effect of mouthwashing with tea tree oil on plaque and inflammation].
AB  - The tea tree oil (melaleuca alternifolia) has antiseptic, fungicide and
      bactericide effects. The efficiency against oral bacteria was also evident.
      Xylitol is known for counterattacking the cariogenic effect caused by the
      streptococcus mutans. Less plaque was developed during the time of the study.

PMID- 14567297
TI  - Bibliography of toxinology.

PMID- 14567296
TI  - Business-related knowledge base of vascular surgeons.

PMID- 14567298
TI  - Bibliography. Current world literature. Oculoplastics and orbital surgery.

PMID- 14567299
TI  - Bibliography. Current world literature. Pediatrics and strabismus.

PMID- 14567301
TI  - Acta Dermatovenerologica Croatica: priority in reporting on new epidemic.

PMID- 14567302
TI  - Overdiagnosis due to prostate-specific antigen screening: lessons from U.S.
      prostate cancer incidence trends.

PMID- 14567303
TI  - Mass screening for prostate cancer: a comparative study in Natori, Japan and
      Changchun, China.

PMID- 14567305
TI  - Acceptability and complications of prostate biopsy in population-based PSA
      screening versus routine clinical practice: a prospective, controlled study.

PMID- 14567304
TI  - Complication rates and risk factors of 5802 transrectal ultrasound-guided sextant
      biopsies of the prostate within a population-based screening program.

PMID- 14567306
TI  - Predictors of cancer in repeat extended multisite prostate biopsy in men with
      previous negative extended multisite biopsy.

PMID- 14567307
TI  - Prostate cancer diagnosed after initial biopsy with atypical small acinar
      proliferation suspicious for malignancy is similar to cancer found on initial
      biopsy.

PMID- 14567308
TI  - Influence of prostate volume in the detection of prostate cancer.

PMID- 14567309
TI  - Substratification of stage T1c prostate cancer based on the probability of
      biochemical recurrence.

PMID- 14567310
TI  - Laparoscopic radical prostatectomy: initial 70 cases at a U.S. university medical
      center.

PMID- 14567311
TI  - Prospective comparison of radical retropubic prostatectomy and robot-assisted
      anatomic prostatectomy: the Vattikuti Urology Institute experience.

PMID- 14567312
TI  - Major postoperative complications secondary to use of the Bookwalter self
      retaining retractor.

PMID- 14567313
TI  - Impact of radical prostatectomy and TURP on the hypothalamic-pituitary-gonadal
      hormone axis.

PMID- 14567314
TI  - Does prophylactic breast irradiation prevent antiandrogen-induced gynecomastia?
      Evaluation of 253 patients in the randomized Scandinavian trial SPCG-7/SFUO-3.

PMID- 14567315
TI  - CT differentiation of large exophytic renal angiomyolipomas and perirenal
      liposarcomas.

PMID- 14567316
TI  - Endocrine-related resources from the National Institutes of Health.

PMID- 14567317
TI  - Von Hippel-Lindau disease: a radiological essay.

PMID- 14567318
TI  - Functioning adrenocortical neoplasms in children.

PMID- 14567320
TI  - Blunt renal trauma-blessing in disguise?

PMID- 14567319
TI  - [Electrocardiogram of the month].

PMID- 14567321
TI  - Management of failed primary intervention for ureteropelvic junction obstruction:
      12-year, single-center experience.

PMID- 14567322
TI  - Outcome at 10 years of severe vesicoureteric reflux managed medically: Report of
      the International Reflux Study in Children.

PMID- 14567323
TI  - Medical versus surgical treatment in children with severe bilateral
      vesicoureteric reflux and bilateral nephropathy: a randomised trial.

PMID- 14567325
TI  - Efficacy and optimal dose of daily polyethylene glycol 3350 for treatment of
      constipation and encopresis in children.

PMID- 14567324
TI  - Cystometric evaluation of reconstructed classical bladder exstrophy.

PMID- 14567326
TI  - Management of recurrent urethral fistulas after hypospadias repair.

PMID- 14567327
TI  - Percutaneous embolization of varicocele in children: A Canadian experience.

PMID- 14567328
TI  - Modified technique for urinary diversion with incontinent conduits.

PMID- 14567329
TI  - Functional outcomes and complications of continent urinary diversions in patients
      with gynecologic malignancies.

PMID- 14567330
TI  - Continent urinary reservoir formation with transverse colon for patients with
      pelvic irradiation.

PMID- 14567331
TI  - Vitamin B12 metabolism after urinary diversion with a Kock ileal reservoir.

PMID- 14567333
TI  - Experience with 'capsule sparing' cystoprostadenectomy for orthotopic bladder
      replacement: overcoming the problems of impotence, incontinence and difficult
      urethral anastomosis.

PMID- 14567332
TI  - The quality of life in men after radical cystectomy with a continent cutaneous
      diversion or orthotopic bladder substitution: is there a difference?

PMID- 14567334
TI  - Prediction of tumour volume and pathological stage in radical prostatectomy
      specimens is not improved by taking more prostate needle-biopsy cores.

PMID- 14567335
TI  - Blood loss during radical retropubic prostatectomy: relationship to morphologic
      features on preoperative endorectal magnetic resonance imaging.

PMID- 14567336
TI  - Implications of radioactive seed migration to the lungs after prostate
      brachytherapy.

PMID- 14567337
TI  - Effect of ketorolac on renal function after donor nephrectomy.

PMID- 14567338
TI  - Utility of hematuria testing in patients with suspected renal colic: correlation
      with unenhanced helical CT results.

PMID- 14567339
TI  - Structural basis of tropism of Escherichia coli to the bladder during urinary
      tract infection.

PMID- 14567340
TI  - Trends in antimicrobial resistance among urinary tract infection isolates of
      Escherichia coli from female outpatients in the United States.

PMID- 14567341
TI  - Adherence of type 1-fimbriated Escherichia coli to uroepithelial cells: more in
      diabetic women than in control subjects.

PMID- 14567342
TI  - Management of bacterial urinary tract infections in adult patients with diabetes
      mellitus.

PMID- 14567343
TI  - Levofloxacin: an updated review of its use in the treatment of bacterial
      infections.

PMID- 14567344
TI  - Physical therapist management of fluoroquinolone-induced Achilles tendinopathy.

PMID- 14567345
TI  - Incidence of acute urinary tract infection in young women and use of male condoms
      with and without nonoxynol-9 spermicides.

PMID- 14567346
TI  - The direct costs of nosocomial catheter-associated urinary tract infection in the
      era of managed care.

PMID- 14567347
TI  - Soy isoflavonoid equol modulates the growth of benign and malignant prostatic
      epithelial cells in vitro.

PMID- 14567348
TI  - Saw palmetto alters nuclear measurements reflecting DNA content in men with
      symptomatic BPH: evidence for a possible molecular mechanism.

PMID- 14567349
TI  - Long-term (7 to 8-year) experience with finasteride in men with benign prostatic
      hyperplasia.

PMID- 14567351
TI  - Sexual function in patients treated for benign prostatic hyperplasia.

PMID- 14567350
TI  - Holmium laser enucleation for large (greater than 100 mL) prostate glands.

PMID- 14567352
TI  - Transurethral interstitial laser coagulation of the prostate and transurethral
      microwave thermotherapy vs transurethral resection or incision of the prostate:
      results of a randomized, controlled study in patients with symptomatic benign
      prostatic hyperplasia.

PMID- 14567353
TI  - Serum human glandular kallikrein (hK2) and insulin-like growth factor 1 (IGF-1)
      improve the discrimination between prostate cancer and benign prostatic
      hyperplasia in combination with total and %free PSA.

PMID- 14567354
TI  - Effect of catheter size on urodynamic assessment of bladder outlet obstruction.

PMID- 14567355
TI  - [Alexander Tschirch and the interpretation of pharmacognosy].

PMID- 14567356
TI  - [The medical provision for children in mid-19th century Wurzburg].

PMID- 14567357
TI  - Management of urethrocutaneous fistula after hypospadias repair: 10 years'
      experience.

PMID- 14567358
TI  - [The institutionalization of epidemiology as a subject at Rio de Janeiro Federal
      University Medical School].
AB  - This article aimed at studying the teaching of epidemiology in medical school
      undergraduate courses. Medical books have been analyzed in order to understand
      the constitution of epidemiology as a scientific subject, as well as its
      relations with medical science and secondary school teaching. The introduction
      and development of the subject in UFRJ Medical School were studied through the
      analysis of internal regulations, courses brochures and programs. Professors were
      interviewed. The analysis revealed that epidemiology concepts spread to health
      services and practice, as well as to medical research. At UFRJ Medical School,
      starting at the end of the 1980's, epidemiology teaching began to be emphasized
      and valued. That was the time when collective health began to develop. Among
      collective health subjects, both epidemiology and statistics developed the most.

PMID- 14567359
TI  - [Lobotomy and leucotomy in Brazilian mental hospitals].
AB  - Lobotomy and leucotomy were used in Brazilian mental institutions from 1936 to
      1956. Also called psycho-surgeries, they were operations that separated the right
      and left frontal lobes and pre-frontal lobes from the rest of the brains, aiming
      at modifying behavior or curing mental diseases. The technique, created by the
      Portuguese neurologist Egas Moniz in 1935 and developed by Walter Freeman from
      the United States, arrived in Brazil through the hands of Aloysio Mattos Pimenta,
      neurologist from Hospital PsiquiatricoJuquely in Sao Paulo. Soon, many doctors
      followed suit. These procedures were used on more than a thousand in-patients
      aiming at not only healing results, but also the technical improvement of the
      surgical technique, since preliminary experiments with animals were quite rare at
      the time. In Brazil, the technique was used until 1956, when it was considered as
      going against the 1947 Nuremberg Code, whose objective was to detain and regulate
      the medical experiments with human beings made during the Second World War.

PMID- 14567360
TI  - WTO drug-access agreement will not solve oncology problems.

PMID- 14567361
TI  - Betel quid and areca nut are carcinogenic without tobacco.

PMID- 14567362
TI  - Australian cancer doctors urged to consider psychosocial care.

PMID- 14567363
TI  - [Nutritional education: from ignorance to social representations in post
      graduation by Rio de Janeiro (1980-98)].
AB  - Tbe present article aims at analyzing the of nutrition teaching in post
      graduation programs from 1980 to 1998. As the maine cause for nutrition as an
      academic subject, nutritional ignorance is the basic focus of dissertations from
      the 1980's up to 1990, showing that the beginning of researchers' education was
      marked by a technical and intervening approach whose subject scope followed an
      outside logic. After 1990, dissertations began to criticize nutrition curriculum
      and practice and to introduce the concept of social representations. On doing so,
      they kept structural concepts when relating representations and practices.
      Tracing back the relevant chronological facts of nutrition, as a science and as a
      profession, ends up to empty informers' statements, revealing that nutritionists
      represent their education and practice more as a result of external idealized
      views than as a group of meaningful representations rendered by their practice,
      in which relational experiences among individuals and with their social
      environment take place.

PMID- 14567364
TI  - Adults with asthma aren't getting flu shots.

PMID- 14567365
TI  - Office-based surgical procedures have far greater risk than those in ambulatory
      surgery centers.

PMID- 14567366
TI  - New national vaccine purchase and distribution system needed, report says.

PMID- 14567367
TI  - Ethics consultations reduce futile life-sustaining treatments.

PMID- 14567368
TI  - Ciclopirox gel in the treatment of patients with interdigital tinea pedis.
AB  - BACKGROUND Tinea pedis (athlete's foot) is the most common fungal infection in
      the general population. Ciclopirox, a broad-spectrum hydroxypyridone antifungal,
      has proven efficacy against the organisms commonly implicated in tinea pedis;
      Trichophyton rubrum, T.mentagrophytes and Epidermophyton floccosum. OBJECTIVE:
      Two multicenter, double-blind, clinical studies compared the efficacy and safety
      of ciclopirox gel with that of its vehicle base in subjects with moderate
      interdigital tinea pedis with or without plantar involvement. METHODS: Three
      hundred and seventy-four subjects were enrolled and randomized to one of two
      treatment groups: ciclopirox gel 0.77%, or ciclopirox gel vehicle, applied twice
      daily for 28 days, with a final visit up to day 50. The primary efficacy variable
      was Treatment Success defined as combined mycological cure and clinical
      improvement >/= 75%. Secondary measures of effectiveness were Global Clinical
      Response, Sign and Symptom Severity Scores, Mycological Evaluation (KOH
      examination and final culture result), Mycological Cure (negative KOH and
      negative final culture results) and Treatment Cure (combined clinical and
      mycological cure). RESULTS: At endpoint (final post-baseline visit), 60% of the
      ciclopirox subjects achieved treatment success compared to 6% of the vehicle
      subjects. At the same time point, 66% of ciclopirox subjects compared with 19% of
      vehicle subjects were either cleared or had excellent improvement. Pooled data
      showed that 85% of ciclopirox subjects were mycologically cured, compared to only
      16% of vehicle subjects at day 43, 2 weeks post-treatment. CONCLUSIONS:
      Ciclopirox gel 0.77% applied twice daily for 4 weeks is an effective treatment of
      moderate interdigital tinea pedis due to T. rubrum, T. mentagrophytes and E.
      floccosum and is associated with a low incidence of minor adverse effects.

PMID- 14567369
TI  - [Marie Rennotte, educator and medical doctor: elements for a historical and
      biographical, social and medical study].
AB  - At the time of Marie Rennotte's 150th birthday celebrations, a new focus on her
      meaningful actions as a Belgian-Brazilian pioneer professional in Education and
      Science in Sao Paulo at the turn of the 19th to the 20th centuries begins to take
      place. The present paper is a preliminary chronological draft with bibliography
      and recommended documents that will allow researchers from different areas to
      develop deeper historic, biographical, medical and social studies demanded by
      Rennotte's extraordinary personal dimensions and the unusual scope of her actions
      in Sao Paulo society.

PMID- 14567370
TI  - Residents as researchers: expectations, requirements, and productivity.

PMID- 14567371
TI  - Synergy between publication and promotion: comparing adoption of new evidence in
      Canada and the United States.
AB  - PURPOSE: Few studies have examined the effect of new evidence from clinical
      trials on physician practice. We took advantage of differences in promotional
      activity in Canada and the United States for the Heart Outcomes Prevention and
      Evaluation (HOPE) study and the Randomized Aldactone Evaluation Study (RALES) to
      determine if publication of new evidence changes practice, and the extent to
      which promotion influences adoption of new evidence. METHODS: We used
      longitudinal dispensing data, collected from 1998 to 2001, to examine changes in
      prescribing patterns for ramipril and other angiotensin-converting enzyme (ACE)
      inhibitors before and after the HOPE study. We also obtained estimates for
      promotional expenditures. We stratified analyses by country, to isolate the
      effect of promotion, and used interrupted time series methods to adjust for pre
      existing prescribing trends. Similar analyses were conducted for spironolactone
      use before and after RALES. RESULTS: Publication of the HOPE study results was
      associated with rapid increases in the use of ramipril. After adjusting for pre
      existing prescribing trends, ramipril prescribing increased by 12% per month (P =
      0.001) in Canada versus 5% per month (P = 0.001) in the United States after the
      study results were presented and published. One year later, ramipril accounted
      for 30% of the ACE inhibitor market in Canada versus 6% in the United States. The
      year before publication of these results, expenditures for detailing increased by
      20% in Canada (to 18 US dollars per physician) but decreased by 7% in the United
      States (to 13 US dollars per physician); the year after publication, spending
      increased to 27 US dollars per physician in Canada versus 23 US dollars per
      physician in the United States. In the absence of promotional activity for RALES
      in either country, publication of results was associated with more modest but
      similar increases of 2% per month (P = 0.001) in spironolactone use in both
      countries. CONCLUSION: Publication of new evidence is associated with modest
      changes in practice. Promotional activity appears to increase the adoption of
      evidence. Rather than relying on the publication of articles and creation of
      guidelines, those wishing to accelerate the adoption of new evidence may need to
      undertake more active promotion.

PMID- 14567372
TI  - [Notes on a book titled Mazhar Osman, Kapali Kutudaki Firtina].
AB  - This paper is a critique of a biographic novel on Mazar Osman, the famous Turkish
      psychiatrist.

PMID- 14567373
TI  - [Prof. Dr. Mim Kemal Oke (1884-1955)and neurosurgery].
AB  - Neurosurgery started in our country in the decade of 20th century. However,
      several neurosurgical procedures were performed by other specialities. Dr. Mim
      Kemal Oke is among the surgeons who performed some neurosurgical procedures
      sporadically. In this study, the life, neurosurgical procedures and publications
      of Mim Kemal were reviewed.

PMID- 14567374
TI  - [An aspect of neurosurgery in Turkey: Dr. Abdulkadir Cahit Tuner (1892-1980)].
AB  - The knowledge regarding the history of different disciplines in medicine is of
      importance. As in each discipline, there are also some pioneers in neurosurgery.
      The name of Dr. Abdulkadir Cahit Tuner, is among the first pioneers in
      neurosurgery. As the first physician who went for training of neurosurgery, Dr
      Tuner made several cranial and spinal operations. In this manuscript, the life
      and the articles of Dr. Abdulkadir Cahit Tuner were reviewed.

PMID- 14567375
TI  - [Books on sexual life and erotic experiences in Islamic literature and Tifasi's
      manuscript].
AB  - Old books on sexual life and erotic experience in Islamic literature.

PMID- 14567376
TI  - [A historical paper dedicated to Kraepelin 76 years ago: history of psychiatry in
      Turkey].
AB  - In this paper, Turkish translation of German article "Die Geschichte der
      Psychiatrie in der Turkei" by Ihsan Sukru Aksel and Fahrettin Kerim Gokay, on the
      dedication issue of Allgemeine Zeitschrift fur Psychiatrie und psychisch
      gerichtliche Medizin for Kraepelin is presented. The place and importance of
      Kraepelin in Turkish psychiatry is also discussed.

PMID- 14567377
TI  - [Obstetrics and gynecology in "Liber Regius" the famous book of Haly Abbas,
      physisian of Xth. century].
AB  - Obstetrics and gynecology in "Liber Regius" the famous book of Haly Abbas,
      physician of Xth century.

PMID- 14567378
TI  - [Claude Bernard and Sakir Pasa].
AB  - The impact of Claude Bernard on the development of physiology in Turkey and the
      influence of Sakir Pasa, professor of physiology in the Medical School of
      Istanbul at the end of XIX century.

PMID- 14567379
TI  - [Dermatological diseases and treatment described in the Turkish manuscripts (XIV
      XVth centuries) (part I)].
AB  - This study deals with skin diseases described in the earliest compiled or
      translated Turkish medical manuscripts of the 14th and 15th centuries in
      Anatolia. The manuscripts studied are: Muntehab-i Sifa, Edviye-i Mufrede,
      Tervihu'l-Ervah, Yadigar, Cerrahiyyetu'l-Haniyye, Kamilu's-Sinaatu't-Tibbiye
      Tercu-mesi, Kitab-i Muntehab-i fi't-Tibb, Haza'inu's-Sa'adat, Akrabadin
      Tercumesi, Mucerrebname, Mufredat-i Ibn-i Baytar Tercumesi, Tuhfe-i Mubarizi,
      Tuhfe-i Muradi. The skin diseases known at that time are studied under the
      following topics: Cuderi (Cicek, Variola, Small-pox); Hasbe (Kizamik, Rubeola,
      Measles); Cuzzam (Lepra, Leprosy, Hansen's disease); Demregu (Temriye,
      Dermatophtosis, Tinea corporis); Behak (There are two types: the white and the
      black; the black is Addison's disease); Baras (Ala, Vitilio); Nemle (Isirga,
      Makul); Ates paresi (Nar-l farisi, frunculosis); Cemre (Kara kabarcik, Sirpence,
      Karbonkul, Carbuncle); Caversiye (Kabarcik hastaligi, blisters disease);
      Sivilceler (Various types of pimples; Humre: Yilancik, Erizipel, Erysipelas, St.
      Anthony's fire; Basbert: Ciban, Fronkul, Boil, Fruncle; Dummel: Kan cibani, Abse,
      Abscess); Abile (Kabarcik, Bule); Seretan (kanser, Cancer); Hanazir (Siraca,
      Scrofuloderma); Akile (Yinurbas, Gangren); Kurdesen (Urtiker, Urticeria); Uyuz
      (Gale, Scabies); Giciyik (Kasinti, Pruritus); Sa'fe (Konak, Seboreik dermatit,
      Scurf); Kel (Alopesi, Favus); Evram (Sisler, Urlar, Tumours); Yara (Karha,
      Cerahat, Wound). The terminology and symptoms of these diseases are studied and
      tried to find their equivalents of today. The causes and the treatment of the
      skin diseases known then are presented.

PMID- 14567380
TI  - [The comparison of the two Ottoman books of anatomy (17-19th centuries) with
      regard to the circulatory system].
AB  - 17th and 19th centuries were particularly important for the development of the
      Ottoman medicine. Westernization which had already started in the 17th century
      continued along the 19th and the early 20th centuries. Turkish physicians began
      to contact with their European colleagues and in this period Latin medical
      terminology began to appear in the Ottoman medical literature. Sirvanli Semseddin
      Itaki's work of the 17th century, the Tesrihu'l Ebdan ve Tercuman-i Kibale-i
      Feylesufan, is the first illustrated Turkish manuscript of anatomy. The
      illustrations are qualified as developed examples, compared with the medical
      literature and knowledge of the period. In the 19th century, Sanizade Mehmet
      Ataullah Efendi (1771-1826) wrote a modern book of anatomy for the Ottoman
      medical doctors. Miyaru'l Etibba was one of the earliest printed medical books in
      Turkish. The second volume of Sanizade's Hamse, Miratu'l Ebdan fi Tesrih-i Azai'l
      Insan is the first printed Ottoman book on anatomy. In Usulu't-Tabia, the third
      volume of Hamse, the circulatory system is discussed. In this article, we studied
      the circulatory system described in Semseddin Itaki's Tesrih-ul Ebdan ve Tercuman
      i Kibale-i Feylesufan and in Sanizade's Usulu't-Tabia and compared them.

PMID- 14567381
TI  - [Poisons and antidotes according to Gunyetu'l Muhassilin and an 18th century
      Ottoman pamphlet].
AB  - This study deals with the chapter on poisons (Sumum) of Gunyetu'l-Muhassilin, a
      translation, and a pamphlet on antidotes called Panzehir, by Ahmed Sani, one of
      the most prominent figures of the Ottoman physicians. As a foreword, the
      terminology related with the subject; and an introduction to the Islamic medical
      theory, the basis of the subject, is discussed. The main topics on poisons are;
      protection against and treatment of poisons; being poisoned by the sting of
      insects, snakes etc. and diseases such as rabies, as a result of bites of animals
      and their treatment; treatment of poisoned suppuration; insecticide drugs and
      measures; and common drugs against all kinds of poisons. Immunization and
      nutrition with respect to being poisoned; and preventive measures against
      insects; and mineral and organic antidotes are also discussed. The classification
      of diseases and treatment ase evaluated on the humoral theory basis. The
      treatment of insect poisoning is viewed from the perspective of its symptoms. The
      pamphlet named Panzehir is about a special antidote, the bezoar stone. This
      antidote is divided into two, of the mineral and the animal origin and the uses
      of the bezoar are discussed. A vocabulary is added to help readers to understand
      the terminology.

PMID- 14567382
TI  - [A systematic analysis of the Ottoman Red Crescent periodical (part I)].
AB  - Founded in 1877, the Ottoman Red Crescent Society rendered a lot of important
      services in military and civil areas in the Ottoman Empire. The Ottoman Red
      Crescent Society not only gave health services for the soldiers, but it also
      attempted to obey the international acts signed for the war captives and to
      rescue them together with the counties involved under the supervision of the
      international Red Cross. In tbe civilian area, the Ottoman Red Crescent Society
      also played an active role to meet the casualties' needs, such as food, clothes,
      and accommodation following natural disaster like earthquake, flood, fire etc.
      The Ottoman Red Crescent Society published a rnonthly newsletter called Osmanli
      Hilal-i Ahmer Mecmuasi to announce its services more effectively to the public
      since 15 September 1921 (12 Muharrem 1346). The publication of the newsletter
      continued as Turkiye Hilal-i Ahmer Mecmuasi after the 15th issue. Starting with
      the 85th issue on September 15th, 1928 (30 Rebiulevvel 1347) it was printed with
      Latin alphabet instead of Arabic letters. A brief translation in French and in
      English exist in the end of each issue.

PMID- 14567383
TI  - [A review of Sanizade Mehmed Ataullah Efendi's book: Kanunu'l Cerrahin].
AB  - Sanizade, who lived in the first half of the 19th century, is an important
      physician for his great contributions to the Ottoman Medicine, by transferring
      European medical knowledge. He has important books concerning history, as well as
      medicine. In one of his works on medicine, Hamse-i Sanizade, a work of five
      volumes, the volume titled Kanunu'l Cerrahin (the Law of Surgery), deals with
      surgery. Written in 1810s, the book could be published only in 1828, after
      Sanizade's death. In the introduction of the book, diseases necessitating surgery
      and surgical operations are described in brief. In the part concerning diseases
      requiring surgery; swellings, diseases of the uro-genital organs, hard and soft
      tumors, injuries and wounds and methods of their treatment are dealt with. As an
      additional part, orthopedical disorders, such as fractures, dislocations and
      other skeletal disorders are described. Surgical operations are written aiming to
      train in the field. The book is not composed in the classical style of the
      Ottoman surgery books, which implies that the book might be a translation from an
      Italian work or it may be an anthology.

PMID- 14567384
TI  - [Biography and publications of Prof. Dr. Selcuk Aybar].

PMID- 14567385
TI  - New mechanism of selective killing of activated hepatic stellate cells.

PMID- 14567386
TI  - Are cultured liver cells the right tool to investigate mechanisms of liver
      disease or hepatotoxicity?

PMID- 14567388
TI  - NME digest.

PMID- 14567387
TI  - From the guest editors.

PMID- 14567389
TI  - Do committees ru(i)n the bio-political culture? On the democratic legitimacy of
      bioethics committees.
AB  - Bioethical and bio-political questions are increasingly tackled by committees,
      councils, and other advisory boards that work on different and often interrelated
      levels. Research ethics committees work on an institutional or clinical level;
      local advisory boards deal with biomedical topics on the level of particular
      political regions; national and international political advisory boards try to
      answer questions about morally problematic political decisions in medical
      research and practice. In accordance with the increasing number and importance of
      committees, the quality of their work and their functional status are being
      subjected to more and more scrutiny. Besides overall criticism regarding the
      quality of their work, particular committees giving political advice are often
      suspected of being incompatible with democratic values, such as respect for
      affected parties, representation of diverse values and transparency in the
      decision-making processes. Based on the example of the German National Ethics
      Council, whose inauguration caused a still ongoing debate on the aims and scopes
      of committees in general, this paper discusses: (1) the requirements of modern
      democratic societies in dealing with complex scientific-technical problems; (2)
      the composition and organisation of committees working as political advisory
      boards; and (3) the appointment procedures and roles of laymen and experts, and
      here in particular of ethicists, who may legitimately be taken on by a committee.
      I will argue that bioethics committees do not necessarily endanger democratic
      values, but can considerably improve their realisation in democratic decision
      making procedures--if, and only if, they do not act as substitutes for
      parliamentarian processes, but help prepare parliamentarian processes to be
      organised as rationally as possible.

PMID- 14567390
TI  - Duties to stakeholders amidst pressures from shareholders: lessons from an
      advisory panel on transplant policy.
AB  - The distinction between stakeholders and shareholders frequently employed in
      business ethics can illuminate challenges faced by a bioethics advisory panel. I
      use the distinction to reflect back on the work of an advisory panel on which I
      served, a panel on US transplant policy. The panel hearings were akin to a
      shareholders' meeting, with many stakeholders absent. In addition to 'hearing
      out' the shareholders who were present, the panel had duties to absent
      stakeholders to insure their interests were included in public discussion. While
      panel efforts to include stakeholder perspectives rightfully framed its report,
      such duties should have framed its operating procedures more robustly. The
      stakeholder/shareholder distinction also offers a critical prism on the actual
      evolution of organ allocation policy, which the panel failed to influence.
      Current policy embodies a compromise among shareholders that obscures major
      stakeholder interests. This results in under-attention to likely medical benefit
      of transplant, compared to other allocation criteria. Recognition of duties to
      stakeholders amidst pressures of shareholders complicates the notion of
      'consensus' for an advisory panel. Consensus framed on terms defined only by
      shareholders, not stakeholders, may be an inadequate measure of public interest.

PMID- 14567391
TI  - Obituary. Charles A. Janeway, Jr. (1943-2003).

PMID- 14567392
TI  - Iron-containing supplements and drugs; label warning statements and unit-dose
      packaging requirements; removal of regulations for unit-dose packaging
      requirements for dietary supplements and drugs. Final rule; removal of regulatory
      provisions in response to court order.
AB  - The Food and Drug Administration (FDA) is removing, in part, a final rule that
      required unit-dose packaging for iron-containing dietary supplement and drug
      products that contain 30 milligrams (mg) or more of iron per dosage unit. FDA is
      taking this action in response to the Court's ruling in Nutritional Health
      Alliance v. FDA, in which the Court concluded that the Federal Food, Drug, and
      Cosmetic Act (the act) does not provide FDA with authority to require
      manufacturers of iron-containing dietary supplement and drug products to use unit
      dose packaging for poison prevention purposes. Today's action takes the
      ministerial step of removing the unit-dose packaging provisions from title 21 of
      the Code of Federal Regulations.

PMID- 14567393
TI  - The spindle checkpoint: from normal cell division to tumorigenesis.
AB  - Faithful chromosome segregation during each cell division is regulated by the
      spindle checkpoint. This surveillance mechanism monitors kinetochore-microtubule
      attachment and the integrity of the mitotic apparatus, delaying mitotic exit
      until all chromosomes are properly aligned at the metaphase plate. Failure of
      this mechanism can generate gross aneuploidy. Since its discovery, mutations in
      genes involved in the spindle checkpoint response were predicted to be serious
      candidates for the chromosomal instability phenotype observed in many tumors.
      During the last few years, significant advances have been made in understanding
      the molecular basis of the spindle checkpoint. However, many studies of tumor
      cell lines and primary cancer isolates have failed to show a direct correlation
      with mutations in spindle checkpoint components. Nevertheless, it was shown that
      many tumor cells have an abnormal spindle checkpoint. Therefore, better
      understanding of the molecular mechanisms involved in regulation of spindle
      checkpoint response are expected to provide important clues regarding the
      mechanisms underlying the emergence of neoplasia.

PMID- 14567394
TI  - Androgen receptor and calcitonin gene-related peptide in neurons of the
      genitofemoral nerve during testicular descent induced with human chorionic
      gonadotropin.
AB  - BACKGROUND: Low levels of circulating testosterone during testis descent cause
      cryptorchidism in humans and rats. Treatment with human chorionic gonadotrophin
      (hCG) induces testis descent by stimulating production of testosterone (T).
      Neurons of genitofemoral nerve (GFN), which innervate testicular gubernaculum,
      may play a role in testis descent. METHODS: In the current study, putative
      correlations were made between T and GFN motor and sensory neuron activity during
      inguinoscrotal testis descent. Cryptorchidism was provoked in prepuberal rats
      with estradiol. Rats with testicular descent induced with hCG and cryptorchid
      controls were used. Cells of spinal cord and dorsal root ganglia were labeled by
      retrograde staining with fast-blue. Expression of androgen receptor (AR) and
      calcitonin gene-related peptide (CGRP) were detected with indirect
      immunofluorescence. RESULTS: Neurons labeled with fast-blue were found in the
      center of motor horn and dorsal root ganglia at levels L1 and L2. While number of
      motor neurons expressing AR was significantly higher in the group treated with
      hCG, number expressing CGRP was higher in controls. In dorsal root ganglion,
      number of cells immunostained with CGRP antibody was similar in both groups but
      AR was not detected. CONCLUSIONS: Present results support the hypothesis that
      motor nucleus of the GFN is a direct target of testosterone and that regulation
      of CGRP in sensory nucleus may be involved in testicular descent.

PMID- 14567395
TI  - Esophageal anastomotic failure: an experimental study.
AB  - BACKGROUND: Postsurgical complications in patients with esophageal atresia have
      remained unchanged during the last three decades. This study was aimed at
      investigating certain risk factors for small-sized esophageal anastomosis and to
      assess the probable relationship between esophageal length and body weight in
      rabbit. METHODS: Six groups of 10 adult rabbits were subjected to section or 1-cm
      segmental resection of thoracic esophagus followed by end-to-end anastomosis.
      Approximation strength of esophageal ends was measured. Three different suture
      materials were used, and three different surgeons carried out procedures.
      Observed morbidity was recorded, as well as leakage or stenosis frequency in
      suture line. Esophageal length and body weight of nonresected rabbits were
      measured. RESULTS: Fifteen leakages were observed in suture line; there were no
      differences in relative risk between groups with and without resection, or in
      ratio of this complication among surgeons; nonetheless, a greater number of
      leakages (p < 0.05) was observed at higher tension. There were no differences in
      magnitude of stenosis among surgeons, tension degree, or suture material used.
      Quadratic association was found between length of thoracic esophagus and body
      weight in nonresected rabbits. CONCLUSIONS: Rabbit esophagus is a suitable model
      to assess early surgical complications but not for late complications. Among
      three assessed factors, increased tension in patients with segmental deficit was
      the most significant factor in development of anastomotic leakage. Existence of
      nonlineal correlation between esophageal length and body weight in rabbit showed
      that resection of 1 cm of esophagus represented a different weight-dependent
      segmental deficit, which increased as weight decreased.

PMID- 14567396
TI  - Interaction of Histoplasma capsulatum yeasts with galactosylated surface
      molecules of murine macrophages.
AB  - BACKGROUND: Histoplasma capsulatum (H.c.) yeast-cell binding to glycosylated
      surface molecules of murine macrophages was studied using attachment inhibition
      assays with different carbohydrate-treated H.c. yeast cells and participation of
      galactose and its derivatives as main sugar inhibitor was always demonstrated.
      METHODS: Liposomes incorporated with macrophage membrane proteins (MMP) were
      constructed to test involvement of macrophage surface glycoprotein molecules in
      H.c. binding. Yeasts attachment to MMP liposomes was successfully evaluated by
      ELISA method. Afterward, inhibition of H.c. yeast-cell attachment to [1,2-3H(N)]
      cholesterol-MMP liposomes was monitored by radioactivity counting of the yeast
      liposome pellet centrifuged at 500 g for 30 min when yeasts were previously
      incubated with different sugars. Other inhibition attachment assays using light
      microscopy and modified ELISA adapted to peritoneal or alveolar macrophage
      monolayers were also performed to determine inhibition mediated by carbohydrates.
      In these assays, Candida albicans (C.a.) was used as control of another type of
      yeast containing a lectin-like molecule. RESULTS: Histoplasma capsulatum yeasts
      attachment to MMP liposomes showed important decrease of radioactive counts when
      treated with galactose and lactose molecules. Light microscopy and modified ELISA
      confirmed inhibition mediated by galactose and its derivatives either in
      peritoneal or alveolar macrophages, and beta-galactose was better recognized than
      its alpha-anomer. In contrast, C.a. attachment to peritoneal or alveolar
      macrophages was not markedly affected by galactose-derivative molecules.
      CONCLUSIONS: Results suggest presence of a lectin-like component in H.c. yeast
      cells and reveal involvement of galactosylated surface molecules of murine
      macrophages as specific-sugar (ligand) residues recognized by the fungal lectin.

PMID- 14567397
TI  - Activation and proliferation of T lymphocyte subpopulations in patients with
      brucellosis.
AB  - BACKGROUND: T-cell proliferation is a standard method to evaluate cellular immune
      responses against intracellular infectious agents. The present study was
      undertaken to look for expression of an early activation marker (CD69) and
      proliferation using a nonradioactive method to evaluate cellular immune response
      against a salt-extractable antigen from Brucella melitensis 16M (RCM-BM) in
      patients suffering from brucellosis. METHODS: Expression of CD69 on membrane of
      CD4+ and CD8+ T-cells was determined by flow cytometry. Lymphoproliferation was
      determined by tritiated thymidine and 5-bromo-2'-deoxyuridine (BrdU)
      incorporation using liquid scintillation counter or flow cytometry, respectively,
      to evaluate DNA synthesis. RESULTS: Thirty healthy donors and 24 patients
      suffering from brucellosis were included in this study. In all cases, incubation
      with mitogen induced expression of CD69 and proliferation of both CD4+ and CD8+ T
      cells. In contrast, only brucellosis patients responded with expression of CD69
      and proliferation against RCM-BM antigen from Brucella melitensis (p < 0.001).
      CONCLUSIONS: Methods used in this study were useful to evaluate immune response
      against specific antigen or polyclonal stimulation. CD4+ and CD8+ T cells from
      patients became equally activated and proliferated in response to RCM-BM antigen.
      Our data suggest that both T-cell subpopulations play an important role in immune
      response against Brucella.

PMID- 14567398
TI  - Association between serum concentration of apolipoproteins A-I and B with
      gallbladder disease.
AB  - BACKGROUND: A total of 1,255 subjects attending a private health care facility in
      Mexico City were studied to evaluate the association of serum concentration of
      Apo A-I and Apo B with presence of gallbladder disease (gallstones or
      cholecystectomy). METHODS: A cross-sectional study was carried out. All
      participants provided data on sociodemographic status and previous diagnoses of
      type 2 diabetes, hypertension, cardiovascular events, alcohol consumption, and
      smoking habits. Women additionally reported their obstetric-gynecologic history.
      Weight and height were measured; liver and biliary tract ultrasound assessed
      gallbladder disease. Plasma levels of total cholesterol, triglycerides, high
      density lipoproteins (HDL) cholesterol, and apolipoproteins A-I (Apo A-I) and B
      (Apo B) were determined after a 12-h fasting period. RESULTS: In multivariate
      models, Apo A-I > or = 120 mg/dL was positively associated with gallbladder
      disease with odds ratio (OR) = 1.64, 95% confidence interval (95% CI) = 1.03
      2.62, whereas Apo B > or = 120 mg/dL showed an inverse association (OR = 0.71,
      95% CI = 0.48-1.05). Ratio of Apo B/Apo A-I > or = 1 was inversely associated
      with risk of gallbladder disease (OR = 0.54, 95% CI = 0.37-0.80). All models were
      adjusted for age, gender, body mass index (BMI), previous diagnosis of type 2
      diabetes, triglycerides, alcohol consumption, tobacco, and contraceptive use, as
      well as for total cholesterol in HDL-cholesterol and Apo A-I models. CONCLUSIONS:
      Our results suggested the relationship between serum concentration of
      apolipoproteins and gallbladder disease. These findings support the hypothesis of
      increased biliary catabolism of cholesterol in subjects with gallbladder disease
      characterized by lower Apo B and higher Apo A-I serum concentrations.

PMID- 14567399
TI  - Vestibular function interferes in cardiovascular reflexes [corrected].
AB  - BACKGROUND: Experimental work indicates that the vestibular system participates
      in autonomic reflexes during body movement and postural changes. However, there
      are no studies of cardiovascular reflexes during vertigo due to human acute
      vestibular lesions. METHODS: We assessed the response to active change of posture
      and hand immersion in cold water in seven patients with unilateral peripheral
      vestibular failure (vestibular neuritis) and seven age/sex-matched healthy
      subjects in acute phase (72 h from vertigo onset) and at 2 weeks of follow-up.
      RESULTS: During acute phase, patients showed decreased blood pressure response
      during cold hand test (p < 0.05). Upright stance induced deficient decrease of
      the respiratory component of heart rate variability (p < 0.05) with lack of
      increase in low frequency/high frequency (LF/HF) ratio. At 2 weeks of follow-up,
      these abnormalities improved. CONCLUSIONS: Results suggest that acute vestibular
      lesions can interfere with cardiovascular autonomic responses in humans. This may
      reflect disruption of normal vestibulo-autonomic reflexes.

PMID- 14567400
TI  - Distortion product otoacoustic emissions test is useful in children undergoing
      cisplatin treatment.
AB  - BACKGROUND: Cisplatin is a widely used chemotherapy agent that has several
      adverse effects, such as ototoxicity. Evaluation of hearing loss due to cisplatin
      therapy in children is difficult. The purpose of this study was to compare the
      validity of distortion product otoacoustic emissions (DPOAEs) with pure tone
      audiometry (PTA) in assessing hearing loss in children under cisplatin therapy.
      METHODS: We reviewed the files of 26 children aged between 2 and 15 years; 14
      were girls. All were under treatment with cisplatin for malignancy. PTA and
      DPOAEs were obtained at the same session. Three subjects were studied twice;
      thus, there were 29 sets of studies. RESULTS: Determining a cut-off point at 45
      dB HL for PTA and 4 dB SPL difference for DPOAEs, diagnostic specificity for the
      latter was 0.97 while sensitivity was 0.57. CONCLUSIONS: DPOAEs represent a
      highly valuable test for evaluating hearing loss due to cisplatin treatment.
      DPOAEs is a quick and objective hearing assessment method not requiring much
      cooperation from children.

PMID- 14567401
TI  - Changing trends in prevalence, morbidity, and lethality in persistent diarrhea of
      infancy during the last decade in Mexico.
AB  - BACKGROUND: Persistent diarrhea (PD) of infancy has incurred high morbidity and
      lethality. However, decrease in its prevalence, morbidity, and lethality appeared
      to occur progressively throughout the last decade of the twentieth century. Our
      objective in this study was to compare prevalence, lethality, and morbidity of
      infants and children with PD managed in a pediatric referral hospital. METHODS:
      We conducted a comparative cross-sectional study. A total of 546 patients with PD
      managed during three different periods (1988-1991, 1993-1994, and 1997-1999) were
      described and analyzed. Prevalence x 100 admissions, prevalence rates of
      nutritional status, sepsis, pneumatosis intestinalis, carbohydrate and protein
      intolerance, and lethality were calculated. We used Student t and chi2 tests
      (alpha = 0.05). RESULTS: Mean age on admission was 13.8 +/- 24.3 months; 296
      (54.2%) patients were males. Prevalence of admissions for PD decreased gradually
      from 31.7 to 13.8%; rates of lethality and mortality remained unchanged.
      Malnutrition had high prevalence throughout the three periods evaluated. Rate of
      carbohydrate intolerance diminished but protein intolerance increased; proportion
      of pneumatosis intestinalis and bowel perforation did not change. Isolation of
      Salmonella spp. and small bowel bacterial overgrowth decreased significantly from
      the 1988-1991 series when compared with later series. CONCLUSIONS: Although these
      observations were made at a pediatric referral hospital, they may suggest that
      prevalence of PD is diminishing. However, its lethality and mortality rates
      remain unchanged. Malnutrition persists as a relevant associated factor. Decrease
      of carbohydrate intolerance and increase in protein intolerance rates resemble
      rates of children with PD of developed countries. These observations may reflect
      an epidemiologic transition of PD in Mexico.

PMID- 14567402
TI  - Discriminant function of perinatal risk that predicts early neonatal morbidity:
      its validity and reliability.
AB  - BACKGROUND: This study aimed to identify significant perinatal risk factors
      associated with neonatal morbidity to construct a scoring system to aid in
      distinguishing between healthy and ill neonates. Validity and reliability of the
      scoring system were determined. METHODS: We conducted a screening test and used
      logistic regression to analyze data from a cohort of 387 neonates and to
      determine the relationship between risk factors and morbidity. Twenty nine
      factors of perinatal risk were studied. Logistic regression and discriminant
      analysis were performed to assess risk for morbidity. This system was developed
      and validated prospectively on 238 new neonates. RESULTS: Risk factors that
      demonstrated association with morbidity by logistic regression were chronic
      maternal illness, premature rupture of membranes (PROM), amniotic fluid, low
      Apgar score at 5 min, obstetric trauma, hypertension, neonatal resuscitation,
      breathing pattern at 6 h after delivery, birth weight, and gestational age.
      Discriminant function obtained from discriminant analysis had sensitivity of 68%
      and specificity of 93%, while positive and negative predictive values were 88 and
      86%, respectively. Area below receiver operating characteristic (ROC) curve was
      0.86 (standard error [SE]: 0.02). In the validity study, these values were
      maintained without significant differences. Kappa statistic between two
      physicians was calculated at 0.84 (p < 0.001). CONCLUSIONS: Evidence indicated
      that discriminant function is a useful tool to assess initial neonatal risk,
      allowing pediatricians to predict morbidity prior to discharge of neonates.

PMID- 14567403
TI  - Chronic disease risk factors among healthy adolescents attending public schools
      in the state of Morelos, Mexico.
AB  - BACKGROUND: Little research (and fewer interventions) has been done on
      longitudinal exposure to risk factors for chronic diseases in young people in
      Latin America, including Mexico, although chronic diseases constitute the first
      cause of death in Mexico. Our objective was to document the prevalence of chronic
      disease risk factors among adolescents as a baseline measurement for a cohort
      study and to develop educational interventions. METHODS: Questionnaires, blood
      samples, and anthropometric measurements were collected from 13,293 public school
      students of both sexes, ages 11-24 years in Morelos, Mexico. This constitutes the
      baseline measurement for a cohort study. Twenty focus groups and 10 in-depth
      interviews were done with girls aged 12-17 years. Two educational interventions
      promoting physical activity and sexual health were designed. RESULTS: Prevalence
      of obesity was 21.2%. On average, participants spent 0.5 h/day on vigorous
      physical activity and 3.7 h/day watching television. Sexual initiation was
      reported by 14.5% (girls = 9.1%, boys = 21.5%); 52.3% of whom reported using
      condoms. Young women demonstrated correct condom use and perceived themselves at
      risk for HIV/AIDS but did not have condom negotiation skills. Prevalence of
      experimenting with tobacco was 15.1% (girls = 10.4%, boys = 21.1%); current
      smoking was 14.4% (girls = 10.6%) and boys = 19.2%), while 6.3% of participants
      reported monthly intoxication with alcohol, and 4.5% reported past and 2.1%
      reported current illegal drug use. CONCLUSIONS: Results indicate substantial
      exposure to risk factors for chronic diseases and reproductive health problems in
      this population. The study will generate interventions and constitutes initiation
      of a longitudinal study able to explore causal associations between risk factors
      and chronic diseases in this population.

PMID- 14567404
TI  - An outbreak due to Serratia marcescens in a neonatal intensive care unit typed by
      2-day pulsed field gel electrophoresis protocol.
AB  - BACKGROUND: Serratia marcescens is a well-recognized nosocomial pathogen. The
      objective of the study was to describe typing results using a rapid pulsed field
      gel electrophoresis (PFGE) protocol and infection control measures during an
      outbreak of Serratia marcescens in a 24-bed, referral, neonatal intensive care
      unit (NICU) of a tertiary-care pediatric hospital. METHODS: Two patients with S.
      marcescens sepsis were identified in the NICU. Health care personnel of the unit
      were requested to reinforce infection control measures. Active surveillance was
      established to detect infected and/or colonized patients and environmental and
      staff reservoirs. Infected and colonized patients were cohorted on one side of
      the unit; admissions to NICU were limited. Isolates were typed with a short 2-day
      pulsed-field gel electrophoresis (PFGE) protocol. RESULTS: Thirty three patients
      were exposed during a period of 20 days. Ten S. marcescens isolates were obtained
      from six patients, in two from blood culture and in three from stool culture; a
      single clone was identified in four. S. marcescens was not isolated from
      environmental or staff cultures. CONCLUSIONS: PFGE results were obtained in 2
      days, infection control measures were reinforced, outbreak was promptly
      interrupted, and the NICU remained opened.

PMID- 14567405
TI  - Successful allogeneic stem cell transplantation with nonmyeloablative
      conditioning in patients with relapsed Hodgkin's disease following autologous
      stem cell transplantation.
AB  - Use of myeloablative preparative therapy and allogeneic stem cell transplantation
      (alloSCT) as salvage therapy for adult patients with relapsed hematologic
      malignancies after autologous stem cell transplantation (autoSCT) is generally
      unsuccessful due to very high treatment-related mortality rates. We report here
      the outcome of HLA-matched related donor alloSCT following nonmyeloablative
      preparative therapy in two patients with Hodgkin's disease, relapsed after
      autologous stem cell graft. Times from autoSCT to alloSCT were 9 and 11 months,
      respectively. Preparative therapy consisted of the following: oral busulfan, 4
      mg/kg on days -6 and -5; intravenous (i.v.) cyclophosphamide, 350 mg/m2 on days 
      4, -3 and, -2, and i.v. fludarabine, 30 mg/m2 on days -4, -3, and -2; oral
      cyclosporin A (CyA) 5 mg/kg was begun on day -1 and i.v. methotrexate 5 mg/m2 was
      delivered on days +1, +3, +5, and +11. Both patients achieved initial mixed
      chimerism as defined as > 1% donor peripheral white blood cells and did not
      receive prophylactic donor lymphocyte infusions; both showed conversion to final
      full-donor chimerism. Stage I acute graft-vs.-host disease occurred in one
      patient and both achieved sustained complete response. One patient died on day
      233 as a consequence of drug-induced pulmonary toxicity, whereas the other
      patient remains in continued complete remission 513 days after allograft. This
      nonmyeloablative alloSCT strategy was well tolerated, was completed entirely on
      an out-patient basis, and can result in durable disease-free survival among
      patients with Hodgkin's disease after failed autoSCT. Further follow-up and
      evaluation of additional patients are required to conclusively establish the role
      of this strategy in treatment of hematologic malignancies after autologous
      transplantation.

PMID- 14567406
TI  - Plowright recognized for impact on global food supply.

PMID- 14567407
TI  - AABP conference delivers relevant-CE.

PMID- 14567408
TI  - Best of the herd honored by AABP.

PMID- 14567409
TI  - Science paves way for another chance at cloning.

PMID- 14567410
TI  - Questions effect of furosemide on racing Thoroughbreds.

PMID- 14567411
TI  - Responses to letters about resolution on ear cropping and tail docking.

PMID- 14567412
TI  - Responses to letters about resolution on ear cropping and tail docking.

PMID- 14567413
TI  - Responses to letters about resolution on ear cropping and tail docking.

PMID- 14567414
TI  - Responses to letters about resolution on ear cropping and tail docking.

PMID- 14567415
TI  - Variables in skin preparations may make comparison of antiseptics difficult.

PMID- 14567416
TI  - Mastermind the future of veterinary medicine.

PMID- 14567417
TI  - Cautions about internship programs.

PMID- 14567418
TI  - What is your diagnosis? Comminuted type-II fracture of the olecranon.

PMID- 14567419
TI  - Effects of dietary fat and polyunsaturated fatty acids in dogs with naturally
      developing chronic renal failure.

PMID- 14567420
TI  - Effects of human contact on animal health and well-being.

PMID- 14567421
TI  - When courts review revocation and suspension orders.

PMID- 14567422
TI  - Prevalence of Campylobacter spp isolated from the intestinal tract of pigs raised
      in an integrated swine production system.
AB  - OBJECTIVE: To enumerate the prevalence of Campylobacter isolates in the
      intestinal tract of market-weight swine raised in an integrated swine operation
      in Texas. SAMPLE POPULATION: Samples of cecal contents were collected from 595
      pigs (mean body weight, 110 kg [242 lb]) at time of slaughter. Pigs were off
      spring of Yorkshire-Landrace sows and Duroc or Hampshire boars. Pigs originated
      from 4 farrow-to-finish farms. PROCEDURE: During a 9-month period, visits were
      made to a slaughter plant to remove cecal contents from market-weight hogs.
      Samples were obtained from 50 pigs/visit from designated farms so that samples
      were obtained 3 times from pigs of each of 4 farms. Isolation of Campylobacter
      spp was accomplished by use of enrichment broth and restrictive media, using
      microaerophilic conditions. RESULTS: Campylobacter spp were isolated from 70 to
      100% of the pigs, depending on the farm and the date the samples were collected.
      Campylobacter coli was isolated from 20 to 100% (mean, 60%) of samples, and C
      jejuni was isolated from 0 to 76% (mean, 31%) of samples. Campylobacter lari was
      isolated from 2 pigs. Concentrations of C coli or C jejuni ranged from 10(3) to
      10(7) colony-forming units/g of cecal content. CONCLUSIONS AND CLINICAL
      RELEVANCE: Campylobacter coli generally is accepted as a common inhabitant of the
      intestinal tract of swine. However, analysis of results of this study suggests
      that a relatively high prevalence of C jejuni may be found in pigs raised on
      specific farms.

PMID- 14567423
TI  - Attitudes, procedures, and delivery of behavior services by veterinarians in
      small animal practice.
AB  - OBJECTIVE: To survey veterinarians in small animal practice concerning their
      attitudes about delivery of behavior services, frequency of common behavior
      problems, manner in which services were provided, confidence in their clinical
      ability to treat these behavior problems, frequency of use of pharmacologic
      intervention, and number of dogs and cats euthanatized specifically because of
      behavior problems. DESIGN: Cross-sectional mail survey. SAMPLE POPULATION: Random
      sample of veterinarians in small animal practice in the United States. PROCEDURE:
      A self-administered mail survey was sent to a random sample of 2,000
      veterinarians. Results were tabulated and statistically analyzed. RESULTS: It was
      estimated that approximately 224,000 dogs and cats were euthanatized annually in
      small animal veterinary practices in the United States because of behavior
      problems. Although veterinarians seemed unwilling to euthanatize animals for
      behavior problems solely on the basis of a client's request, many veterinarians
      did not routinely inquire about animal behavior and often were not confident in
      their clinical skills to treat behavior problems. Female veterinarians tended to
      be more proactive in addressing behavior problems and to have more positive
      attitudes than male veterinarians about the importance of animal behavior.
      CONCLUSIONS AND CLINICAL RELEVANCE: Efforts are needed to increase the number of
      veterinarians who systematically incorporate inquiries about animal behavior into
      routine clinical practice and to build the confidence of veterinarians for
      diagnosing and treating animal behavior problems.

PMID- 14567424
TI  - Clinical comparison of three methods to measure blood pressure in nonsedated
      dogs.
AB  - OBJECTIVE: To determine arterial blood pressure in client-owned dogs, using
      direct arterial puncture, oscillometry, and Doppler ultrasonography in a clinical
      setting. DESIGN: Prospective study. ANIMALS: 8 clinically normal client-owned
      dogs. PROCEDURE: Blood pressures of nonsedated dogs were measured simultaneously,
      using each of the 3 methods. Mean values obtained were compared with published
      mean values. Ability of noninvasive methods (Doppler ultrasonography and
      oscillometry) to accurately predict results of the invasive method, and
      relationships between blood pressure and age, body weight, and degree of patient
      anxiety were determined. RESULTS: Calculated ranges of values (mean +/- 2 SD)
      determined by direct arterial puncture were: systolic pressure, 114 to 194 mm Hg;
      diastolic pressure, 66 to 102 mm Hg; and mean pressure, 85 to 129 mm Hg. Ranges
      determined by use of oscillometry were: systolic, 110 to 190 mm Hg; diastolic, 35
      to 107 mm Hg; and mean, 78 to 138 mm Hg. Ultrasonographic and oscillometric
      values did not accurately predict direct values, but mean values of systolic and
      mean pressures were similar among methods. Relationships were not detected
      between age or body weight and blood pressure. Significant differences in blood
      pressure were not detected between anxious and nonanxious dogs. CONCLUSIONS AND
      CLINICAL RELEVANCE: Mean values of systolic, diastolic, and mean arterial blood
      pressure measured in nonsedated client-owned dogs, using invasive and noninvasive
      methods in a clinical setting, are comparable with those determined for
      acclimatized, trained, or sedated dogs. However, results of noninvasive methods
      may not accurately reflect direct values.

PMID- 14567425
TI  - Immunohistochemical detection of proliferating cell nuclear antigen and Ki-67 in
      mast cell tumors from dogs.
AB  - OBJECTIVE: To determine whether immunohistochemical detection of proliferating
      cell nuclear antigen (PCNA) and Ki-67 correlated with prognosis for dogs with
      cutaneous mast cell tumors (MCT). DESIGN: Case series. ANIMALS: 120 dogs with
      solitary cutaneous MCT that were excised. PROCEDURE: Information on signalment,
      history, and outcome was obtained by sending a questionnaire to referring
      veterinarians. Tumors were graded histologically, and immunohistochemical
      staining for Ki-67 and PCNA was performed. RESULTS: Survival rates 12, 18, and 24
      months after surgery were significantly different among groups when dogs were
      grouped on the basis of histologic grade. Although mean number of PCNA-positive
      nuclei/1,000 tumor nuclei was significantly higher for dogs that died of MCT than
      for those that survived, there was great overlap in values. Mean number of Ki-67
      positive nuclei/1,000 tumor nuclei was significantly higher for dogs that died of
      MCT than for those that survived, without any overlap in values between groups,
      and number of Ki-67-positive nuclei/1,000 tumor nuclei was significantly
      different among groups when tumors were grouped on the basis of histologic
      grades. For dogs with grade-II tumors, number of Ki-67-positive nuclei/1,000
      tumor nuclei (< 93 vs > or = 93) was significantly associated with outcome
      (survived vs died). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that for
      dogs with solitary cutaneous MCT, determining number of Ki-67-positive nuclei may
      be useful in predicting prognosis, particularly for dogs with grade-II tumors.

PMID- 14567426
TI  - Use of a modified stomach tube for bronchoalveolar lavage in dogs.
AB  - A technique that did not require use of a bronchoscope for bronchoalveolar lavage
      (BAL) in dogs was developed. An inexpensive, readily available 16-F Levin-type
      stomach tube was modified for the procedure. The technique was effective for
      collecting BAL fluid in 9 dogs that ranged from 9.3 to 26.2 kg (20.5 to 57.6 lb).
      Recovered fluid was consistent with fluid collected bronchoscopically. Mean
      recovery volume was 84/125 ml (67%), mean WBC counts were high (> 300
      cells/microl), and > 70% of cells were macrophages. Complications from use of the
      technique were not detected on the basis of pulse oximetry, thoracic radiography,
      and clinical observation. This effective, simple, and safe technique for BAL can
      be readily performed in clinical settings that do not have bronchoscopic
      capabilities. It also provides a less costly alternative than bronchoscopic BAL.

PMID- 14567427
TI  - Subtotal colectomy and ileocolonic anastomosis in a Vietnamese pot-bellied pig
      with idiopathic megacolon.
AB  - A 7-month-old sexually intact female Vietnamese pot-bellied pig was evaluated
      because of constipation. On abdominal palpation, a hard tubular structure was
      palpated in the middle of the abdomen. Abdominal radiography revealed loops of
      intestine that were markedly distended with ingesta, consistent with obstructive
      intestinal disease. On exploratory celiotomy, a massively distended cecum and
      spiral colon were found. A subtotal colectomy, with a side-to-side ileocolonic
      anastomosis, was performed. The cause of the megacolon was not discovered. The
      pig did well following surgery and eventually defecated normally following an
      initial period of diarrhea. To our knowledge, this is the first report of
      therapeutic removal of a substantial portion of the large intestine in swine. Our
      decisions concerning the pig of this report were based largely on our knowledge
      of megacolon in cats. The outcome for this pig indicates that subtotal colectomy
      along with removal of the cecum and ileocecal valve can be used to successfully
      treat idiopathic megacolon in Vietnamese pot-bellied pigs.

PMID- 14567428
TI  - Rickets caused by excessive renal phosphate loss and apparent abnormal vitamin D
      metabolism in a cat.
AB  - Rickets was diagnosed in a 1-year-old cat with a history of weakness, osteopenia,
      and recurrent fractures. Processes causing rickets include vitamin D deficiency
      caused by inadequate, nutrition, lack of exposure to sunlight, defective
      metabolism of parent vitamin D to active metabolites, inherited vitamin D
      receptor defects, hypoparathyroidism, chronic renal failure, renal loss of
      phosphate, or malabsorptive states resulting from gastrointestinal or hepatic
      diseases. On the basis of analysis of serum 25-hydroxyvitamin D3 and 1,25
      dihydroxyvitamin D2 and D3 concentrations, serum biochemical analysis, and
      urinary fractional clearance of electrolytes, the causes of rickets in our cat,
      were most compatible with a combination of excessive loss of phosphorus via the
      kidneys and deficient or abnormal hepatic 25-hydroxylation of vitamin D.
      Calcifediol treatment and twice daily administration of phosphate salts resulted
      in clinical improvement and increases in mineralization of the skeleton, as
      evidenced on radiographic evaluation.

PMID- 14567429
TI  - Pulmonary thromboembolism in cats: 29 cases (1987-1997).
AB  - OBJECTIVE: To determine clinical signs, clinicopathologic abnormalities,
      radiographic findings, histologic abnormalities, and predisposing factors or
      diseases in cats with pulmonary thromboembolism (PTE). DESIGN: Retrospective
      study. ANIMALS: 29 cats in which PTE was confirmed at necropsy. PROCEDURE:
      Information on signalment, body weight, history, results of physical examination,
      results of CBC and serum biochemical analyses, whether PTE was suspected prior to
      death, type of indwelling venous catheter and duration of venous catheterization,
      results of thoracic radiography, and whether cats had any concurrent diseases was
      obtained from medical records. RESULTS: PTE was identified in cats of various
      ages (median, 8.7 years), weights (median, 4.1 kg [9 lb]), and breeds. The most
      common owner-reported problems included lethargy (17 cats), anorexia (14), weight
      loss (10), and difficulty breathing (8); physical abnormalities included lethargy
      (21), tachypnea or dyspnea (16), and dehydration (13). Clinicopathologic
      abnormalities reflected concurrent or underlying diseases. Common radiographic
      abnormalities included pulmonary vessel abnormalities (11), pleural effusion (8),
      and peripheral noncircumscribed consolidations (6). Underlying or predisposing
      conditions, including cardiac disease (12), neoplasia (10), corticosteroid
      administration (8), disseminated intravascular coagulation (5), protein-losing
      nephropathy (4) or enteropathy (4), immune-mediated hemolytic anemia (2), and
      sepsis (2) were identified in all cats. CONCLUSIONS AND CLINICAL RELEVANCE:
      Results suggest that PTE can develop in cats of any age, sex, or breed. Because
      PTE is a serious, potentially life-threatening disease, it should be suspected in
      cats with thoracic radiographic changes suggestive of uneven distribution of
      blood flow between lung lobes, especially in cats that have predisposing factors
      or diseases.

PMID- 14567430
TI  - Comparison of perioperative versus postoperative intratumoral administration of
      cisplatin for treatment of cutaneous sarcoids and squamous cell carcinomas in
      horses.
AB  - OBJECTIVE: To determine the benefits of reducing the interval between surgical
      cytoreduction and intratumoral administration of cisplatin. DESIGN: Randomized
      clinical study. ANIMALS: 70 horses with 89 incompletely resected T2- and T3-stage
      sarcoids (n = 64) and squamous cell carcinomas (25). PROCEDURE: Horses were given
      4 intratumoral treatments of cisplatin at 2-week intervals. The first treatment
      was given at the time of, or immediately after, surgical resection for horses
      treated in accordance with the perioperative protocol (group 1). Horses in group
      2 were treated with cisplatin after the skin healed following surgical resection
      in accordance with the postoperative protocol. RESULTS: A difference was not
      found in duration of overall local tumor control between the 2 groups. Patterns
      of treatment failures and interval to failure differed between the 2 groups.
      Length of the surgical scar was the only factor that affected prognosis; an
      increase in length was associated with a poorer prognosis. A detrimental effect
      of postoperative treatment was only found in tumors with a high tumor
      proliferative fraction. Local reactions were similar for the 2 treatment groups,
      and chronic reactions were not observed. CONCLUSIONS AND CLINICAL RELEVANCE:
      Intratumoral administration of cisplatin is beneficial for treatment of cutaneous
      tumors in horses. Tumor repopulation during the interval between surgery and
      intratumoral administration of cisplatin decreases treatment efficacy. These
      results provide evidence of rapid tumor repopulation following surgical resection
      without a lag period for tumors with a high proliferation index. When tumor
      proliferation index is not known, it may be prudent to use the perioperative
      protocol.

PMID- 14567431
TI  - Clinical and pathologic findings in two draft horses with progressive muscle
      atrophy, neuromuscular weakness, and abnormal gait characteristic of shivers
      syndrome.
AB  - Two Belgian geldings, 4 and 14 years old, respectively, with muscle atrophy,
      weakness, and abnormal gait characteristic of severe advanced shivers were
      examined clinically and on necropsy. Neurologic examination revealed no evidence
      of ataxia, and the clinical diagnosis was neuromuscular weakness and shivers.
      Necropsies of both horses, including examination of pituitary, brain, spinal
      cord, spinal roots and ganglia, and peripheral nerves, revealed no gross or
      histologic abnormalities. Examination of multiple skeletal muscle specimens
      revealed chronic myopathic changes and periodic acid-Schiff positive, amylase
      resistant inclusions within muscle fibers, characteristic of equine
      polysaccharide storage myopathy. It is suggested that underlying metabolic
      myopathy may be the cause of muscle weakness and cramping in horses with shivers.

PMID- 14567432
TI  - Empyema of the guttural pouch (auditory tube diverticulum) in horses: 91 cases
      (1977-1997).
AB  - OBJECTIVE: To identify features of guttural pouch (auditory tube diverticulum)
      empyema in horses and compare findings of uncomplicated guttural pouch empyema
      with guttural pouch empyema complicated by chondroids. DESIGN: Retrospective
      study. ANIMALS: 91 horses with guttural pouch empyema. PROCEDURE: Medical records
      of horses with guttural pouch empyema were reviewed. RESULTS: The most common
      owner complaint and abnormal finding was persistent nasal discharge. Chondroids
      were detected in 21% (19/91) of affected horses. Streptococcus equi was isolated
      from the guttural pouch in 14 of 44 horses; for Streptococcus spp, in vitro
      resistance to sulfadimethoxine and trimethoprim-sulfamethoxazole was detected.
      Retropharyngeal swelling and pharyngeal narrowing were significantly more
      prevalent in horses with chondroids, compared with horses with uncomplicated
      empyema. Ninety-three percent of affected horses were discharged from the
      hospital; at time of discharge, 66% had complete resolution of disease, 19% had
      improvement without resolution, and 15% did not have improvement. CONCLUSIONS AND
      CLINICAL RELEVANCE: Horses with persistent nasal discharge should be examined
      endoscopically for guttural pouch empyema. Treatment with lavage offers a good
      prognosis for resolution of uncomplicated guttural pouch empyema. Aggressive
      treatment with lavage and endoscopic snare removal of chondroids offers a good
      prognosis and may make surgical intervention unnecessary.

PMID- 14567433
TI  - Usefulness of aerobic microbial culture and cytologic evaluation of corneal
      specimens in the diagnosis of infectious ulcerative keratitis in animals.
AB  - OBJECTIVE: To determine the diagnostic value of aerobic microbial culture and
      cytologic evaluation of corneal specimens in the diagnosis of infectious
      ulcerative keratitis (IUK). DESIGN: Prospective study. ANIMALS: 48 animals (26
      dogs, 13 horses, 7 cats, 1 bird, and 1 llama) with corneal ulcers. PROCEDURE:
      Scrapings from corneal ulcers were examined cytologically. Corneal swab specimens
      were submitted for microbial culture. Animals were grouped according to whether
      they had been receiving antimicrobials at the time of admission. RESULTS: Of the
      38 animals receiving antimicrobials, 19 had positive results for IUK on cytologic
      evaluation, 20 on microbial culture, and 26 on cytologic evaluation, microbial
      culture, or both. Of the 10 animals not receiving antimicrobials at the time of
      admission, 7 had positive results for IUK on cytologic evaluation, and 9 had
      positive results on microbial culture. In this group of 10 animals, additional
      animals with IUK were not identified on the basis of cytologic evaluation alone.
      When all 48 animals were considered irrespective of antimicrobial treatment, 26
      and 29 had positive results for IUK on cytologic evaluation and microbial
      culture, respectively, whereas IUK was confirmed in 35 animals on the basis of
      cytologic evaluation, microbial culture results, or both. CONCLUSIONS AND
      CLINICAL RELEVANCE: Microbial culture and cytologic evaluation of corneal
      specimens maximizes identification of IUK, especially in animals receiving
      antimicrobial treatment. Because of serious consequences of untreated IUK, we
      recommend that both diagnostic tests be used to tailor treatment and reduce risk
      of vision impairment in animals.

PMID- 14567434
TI  - Phase I dose-escalation trial of ZD9331 in Japanese patients with refractory,
      solid malignancies.
AB  - BACKGROUND: ZD9331 is a novel thymidylate synthase inhibitor that, unlike some
      other antifolates, does not require polyglutamation for activity. This phase I
      dose-escalation trial investigated the tolerability, efficacy and
      pharmacokinetics of ZD9331 in Japanese patients with refractory, solid
      malignancies. PATIENTS AND METHODS: The mean age of patients was 57.6 years, and
      the most common primary tumours were gastric and colorectal cancer. Most patients
      had received prior chemotherapy and/or surgery. ZD9331 (69, 108 and 130
      mg/m2/day) was administered as a 30-min i.v. infusion on days 1 and 8 of a 3-week
      cycle. RESULTS: A total of 18 patients received ZD9331 treatment; six at each
      dose level. Patients received a median of 2 cycles of treatment ZD9331
      demonstrated some antitumour activity, with one-third of patients showing no
      significant change in tumour size. ZD9331 was associated with non-dose-dependent
      myelosuppression, and dose-limiting toxicity was observed in one patient given 69
      mg/m2/day and one patient given 130 mg/m2/day. The maximum plasma concentration
      and total area under the concentration-time curve increased with ZD9331 dose,
      whereas other pharmacokinetic parameters remained constant and independent of
      dose. Pharmacokinetic parameters were comparable following day 1 and 8 doses,
      with no accumulation of ZD9331 following the second dose. CONCLUSION: ZD9331 has
      a manageable toxicity profile and shows some evidence of activity in Japanese
      patients with refractory, solid malignancies. The pharmacokinetic profile of
      ZD9331 in Japanese patients is similar to that observed in Western patients.

PMID- 14567435
TI  - Phase II multicentre trial of ZD9331 monotherapy as first-line treatment for
      gastric cancer.
AB  - BACKGROUND: ZD9331 is a novel, direct-acting and specific inhibitor of
      thymidylate synthase that has shown clinical activity and manageable tolerability
      in solid tumours. This phase II trial was designed to determine the antitumour
      activity and tolerability of ZD9331 given as a first-line therapy to patients
      with advanced gastric cancer. PATIENTS AND METHODS: Eligible patients who were
      chemonaive with histologically or cytologically proven gastric cancer entered an
      open-label, multicentre, two-stage trial. Initially, patients were dosed at 130
      mg/m2 (Regimen 1); however, following a protocol amendment, the starting dose was
      reduced to 65 mg/m2 (Regimen 2). Patients received ZD9331 as a 30-min i.v.
      infusion once weekly for 2 weeks followed by 1 week without treatment (3-week
      cycle). RESULTS: Twenty-nine patients with advanced, relapsed or inoperable
      gastric cancer were recruited from 11 centres across Europe. Five patients
      (17.2%), all from Regimen 2, showed a partial response and 16 patients (55.2%)
      had a best response of disease stabilisation. Most patients (72.4%) had a best
      response of disease control with median time to progression being 98 days. ZD9331
      had manageable toxicity with the most frequently reported adverse events being
      neutropenia (62%) and diarrhoea (38%). CONCLUSIONS: ZD9331, as a first-line
      treatment for patients with advanced gastric cancer, demonstrated clinical
      activity and manageable toxicity.

PMID- 14567436
TI  - A review of phase II studies of ZD9331 treatment for relapsed or refractory solid
      tumours.
AB  - BACKGROUND: Non-small cell lung cancer (NSCLC), ovarian and breast cancers,
      especially in advanced stages, are difficult to treat using chemotherapy, and
      novel treatments are required to improve the outcome for the large numbers of
      patients who relapse after receiving the most effective first- and second-line
      treatments currently available. This paper reviews the results from three trials
      of ZD9331, a novel, direct-acting antifolate, in patients with relapsed or
      refractory solid tumours. PATIENTS AND METHODS: Patients with relapsed or
      refractory NSCLC, ovarian or breast cancer were included in these three open
      label, multicentre trials. All three trials included an i.v. arm of ZD9331 at a
      dose of 130 mg/m2; the ovarian study also included a 65 mg/m2 i.v. treatment arm
      and the breast cancer trial included a 3 mg oral treatment arm. Patients received
      ZD9331 as a 30-min i.v. infusion once weekly for 2 weeks followed by 1 week
      without treatment (3-week cycle). Oral ZD9331 was given once daily for 28
      consecutive days and repeated every 6 weeks. RESULTS: One hundred and eighty-nine
      patients were included in the three trials (NSCLC: n = 46; ovarian: n = 80;
      breast: n = 63). Neutropenia (45-59%), asthenia (25-42%) and nausea (41-59%) were
      amongst the most common adverse events observed in all three trials; however, in
      the oral treatment group of the breast cancer trial anaemia (58%) and increased
      alanine aminotransferase (45%) or aspartate aminotransferase (39%) were also
      frequent. There were no objective responses seen in the NSCLC trial; 20 of 46
      patients (43.5%) experienced a best overall response of stable disease. Objective
      response rates (ORRs) in the ovarian trial were 2.5% (one patient) and 10% (four
      patients) in the 65 and 130 mg/m2 treatment arms, respectively. In the breast
      cancer trial ORRs were 9.7% (three patients) and 12.5% (four patients) in the
      oral and i.v. groups, respectively. CONCLUSIONS: ZD9331 has a manageable toxicity
      profile, and shows some evidence of activity in patients with relapsed or
      refractory NSCLC, ovarian and breast cancer.

PMID- 14567437
TI  - ZD9331 in combination with topotecan: phase I and II experience.
AB  - BACKGROUND: ZD9331, a novel, direct-acting thymidylate synthase inhibitor, and
      the topoisomerase inhibitor topotecan have antitumour activity in a range of
      solid tumours. We report results from two open-label, multicentre, phase I and
      phase II trials, investigating the pharmacokinetics, tolerability and efficacy of
      ZD9331, when used in combination with topotecan in patients with relapsed or
      refractory tumours. PATIENTS AND METHODS: Patients in the phase II trial had
      progressed following first- or second-line treatment with platinum and
      paclitaxel. The recommended dose (RD) from the phase I study was subsequently
      used in the phase II trial. ZD9331 was given as a 30-min i.v. infusion on days 1
      and 8 combined with a 30-min i.v. infusion of topotecan on days 1-5 of each 3
      week cycle. RESULTS: Sixteen patients with a selection of solid tumours were
      recruited to the phase I trial. Forty-one patients were included in the
      combination therapy arm of the phase II study; 95% of which had ovarian cancer
      and 5% had peritoneal cancer. Three patients experienced dose-limiting toxicity
      during the phase I trial, one at dose level 1 (ZD9331 65 mg/m2, topotecan 0.5
      mg/m2) and two at dose level 2 (ZD9331 65 mg/m2, topotecan 0.75 mg/m2). The RD
      for the phase II study was ZD9331 65 mg/m2, topotecan 0.5 mg/m2. In both trials,
      the most common grade 3 and 4 adverse events were thrombocytopenia (15 of 57
      patients, 26.3%), neutropenia (11 of 57 patients, 19.3%) and anaemia (9 of 57
      patients, 15.8%). One patient (2.4%) in the phase II trial experienced a complete
      response and six patients overall experienced a partial response [one (6.3%) in
      phase I, five (12.2%) in phase II]. Seventeen patients achieved stable disease
      [three (18.8%) in phase I, 14 (34.1%) in phase II]. CONCLUSIONS: ZD9331, in
      combination with topotecan, showed manageable toxicity and some evidence of
      activity in patients with ovarian cancer.

PMID- 14567438
TI  - Cell surface NADH oxidases (ECTO-NOX proteins) with roles in cancer, cellular
      time-keeping, growth, aging and neurodegenerative diseases.
AB  - ECTO-NOX (because of their cell surface location) proteins comprise a family of
      NAD(P)H oxidases of plants and animals that exhibit both oxidative and protein
      disulfide isomerase-like activities. The two biochemical activities, hydroquinone
      [NAD(P)H] oxidation and protein disulfide--thiol interchange alternate, a
      property unprecedented in the biochemical literature. A tumor-associated ECTO-NOX
      (tNOX) is cancer-specific and drug-responsive. The constitutive ECTO-NOX (CNOX)
      is ubiquitous and refractory to drugs. The physiological substrate for the
      oxidative activity appears to be hydroquinones of the plasma membrane such as
      reduced coenzyme Q10. ECTO-NOX proteins are growth-related and drive cell
      enlargement. Also indicated are roles in aging and in neurodegenerative diseases.
      The regular pattern of oscillations appears to be related to alpha-helix-beta
      structure transitions and serves biochemical core oscillator of the cellular
      biological clock. Period length is independent of temperature (temperature
      compensated) and synchrony is achieved through entrainment.

PMID- 14567439
TI  - Leptin regulates functional capacities of polymorphonuclear neutrophils.
AB  - Recent studies report that leptin may be able to modulate some functions of cells
      involved in non-specific immune response. We recently found that a functional
      leptin receptor is present on polymorphonuclear neutrophils (PMNs) and may be
      able to influence their oxidative capacities. We demonstrate here for the first
      time that leptin is also able to stimulate chemotaxis of PMNs and exerts by
      itself a chemoattractive effect comparable to that of well-known formyl-methionyl
      leucyl-phenylalanine, and a stimulating effect on intracellular hydrogen peroxide
      production, without modification of phagocytosis.

PMID- 14567440
TI  - A validated method for rapid analysis of ethane in breath and its application in
      kinetic studies in human volunteers.
AB  - Oxidative stress may initiate lipid peroxidation that generates ethane. Ethane,
      at low concentrations, is eliminated by pulmonary exhalation. Previous methods
      have not allowed frequent sampling, thus ethane kinetics has not been studied in
      man. A validated method over the range 3.8-100,000 ppb with a limit of
      quantitation of 3.8 ppb (CV 9.3%) based on cryofocusing technique of a 60 ml
      breath sample allowed frequent sampling. Due to a rapid analytical procedure
      batches of more than 100 samples may be analyzed. In human volunteers (24-55
      years) uptake was studied for up to 23 min (n = 9), elimination was studied for
      210 min (n = 9). Ethane was inhaled (concentrations varied from 16 to 29 ppm
      (parts per million)) through a non-rebreathing system; sampling was performed
      with short intervals from the expiratory limb. Samples were also drawn from the
      inhalatory limb. Ninety-five percent of steady state (inspired) concentration was
      reached within 1.75 min. Five percent of the initially inhaled concentrations was
      found in exhaled air 1.5 min after termination of inhalation. A terminal mean
      half life of 31 min for ethane was also observed. The data indicate that frequent
      sampling will be necessary to capture relevant changes in breath ethane.

PMID- 14567441
TI  - An inter-subunit disulfide bond affects affinity of human lung extracellular
      superoxide dismutase to heparin.
AB  - Human extracellular superoxide dismutase (EC-SOD) was purified to homogeneity
      from lung tissue and the nature of the binding of heparin to EC-SOD was
      investigated. The enzyme was purified using three column chromatographic steps,
      and 127 microg of purified EC-SOD was obtained. A specific anti-human EC-SOD
      antibody was obtained by immunization with the purified enzyme. Western blot
      analysis of the heparin affinity chromatography product indicated that the
      presence of the inter-subunit disulfide bond affects the affinity of EC-SOD for
      heparin. The affinity of EC-SOD for heparin is a very important feature of the
      enzyme because it controls the distribution of the enzyme in tissues. The present
      study suggests that, not only the processing of the C-terminal region but inter
      subunit disulfide bonds also play a role in determining the tissue distribution
      of EC-SOD. Moreover, the results obtained here also suggest that the redox state
      of the tissues might regulate the function of the EC-SOD.

PMID- 14567442
TI  - Antioxidative properties of Martynoside: pulse radiolysis and laser photolysis
      study.
AB  - Free radical reactions of Martynoside (MAR), a phenylpropanoid glycoside, with a
      variety of oxidants were studied in the aqueous solution by laser photolysis and
      pulse radiolysis techniques. The pKa value of MAR in aqueous solution was
      measured from the pH dependent changes of the UV absorption at 384 nm with value
      of pKa = 9.2. The phenoxyl radical of MAR which exhibits maximum absorption at
      360 nm was generated by one-electron transfer to N3* or Br2*-. Other important
      properties of phenoxyl radical such as extinction coefficient, formation and
      decay rate constants were also determined. The reaction rate constant of O2*-
      with MAR, k = 8.5 x 10(4) dm3 x mol(-1) x s(-1), was measured by the method of
      competition kinetics. By measuring time-resolved luminescence emission at 1270
      nm, the quenching rate constant of singlet oxygen by MAR was obtained to be 3.3 x
      10(6) dm3 x mol(-1) x s(-1). Reduction potential of the MAR couple (MAR*/MAR),
      determined using rutin as reference compound, gave a value E = 0.66 V vs. NHE.
      The antioxidative properties of MAR were compared with those of some well-known
      antioxidants.

PMID- 14567443
TI  - Influence of carbohydrate ingestion on oxidative stress and plasma antioxidant
      potential following a 3 h run.
AB  - Concentrations of reactive oxygen species (ROS) increase during exercise
      secondary to increased oxygen uptake, xanthine oxidase activity, and immune
      system activation. Carbohydrate compared to placebo beverage ingestion is
      associated with an attenuated cortisol and catecholamine response. Catecholamines
      can undergo autooxidation to form ROS. We hypothesized that during intense
      exercise, ingestion of carbohydrate compared to placebo would diminish oxidative
      stress. Sixteen experienced marathoners ran on treadmills for 3 h at
      approximately 70% VO2(max) on two occasions while receiving carbohydrate or
      placebo beverages (11/h, double-blinded) in a randomized, counterbalanced order.
      Blood samples were collected before and immediately after exercise, snap frozen
      in liquid nitrogen, and stored at -80 degrees C until analysis. Plasma samples
      were analyzed for F2-isoprostanes (FIP) and lipid hydroperoxides (ROOH) as
      measures for lipid peroxidation, ferric reducing ability of plasma (FRAP) as a
      measure of plasma antioxidant potential and for cortisol. The pattern of change
      in cortisol was significantly different between carbohydrate and placebo
      conditions (P = 0.024), with post-exercise levels higher in the placebo
      condition. Under both carbohydrate and placebo conditions, significant increases
      in FIP, ROOH, and FRAP were measured, but the pattern of increase was not
      different (FIP, interaction effect, P = 0.472; ROOH, P = 0.572; FRAP, P = 0.668).
      Despite an attenuation in the cortisol response, carbohydrate compared to placebo
      ingestion does not counter the increase in oxidative stress or modulate plasma
      antioxidant potential in athletes running 3 h at 70% VO2(max).

PMID- 14567444
TI  - TNP-470 inhibits oxidative stress, nitric oxide production and nuclear factor
      kappa B activation in a rat model of hepatocellular carcinoma.
AB  - The objective of this study is to determine if treatment with the angiogenesis
      inhibitor TNP-470 results in impairment of oxidative stress, inhibition of
      nuclear factor kappa B (NF-kappaB) activation and decrease of nitric oxide
      production in an experimental model of rat hepatocarcinogenesis. Tumour was
      induced by diethylnitrosamine and promoted by two-thirds hepatectomy plus
      acetaminofluorene administration. Experiments were carried out at 28 weeks after
      initiating the treatment. TNP-470 was administered at 30mg/kg, three times per
      week from 20 to 28 weeks. Carcinomatous tissue growing outside dysplastic nodules
      and a marked expression of placental glutathione S-transferase were detected in
      rats with induced carcinogenesis. Liver concentrations of thiobarbituric acid
      reactive substances, reduced glutathione (GSH) and glutathione disulfide (GSSG)
      were significantly higher than those of controls and there was a significant
      increase in the GSSG/GSH ratio. Tumour growth was accompanied by augmented
      expression of inducible nitric oxide synthase, activation of (NF-kappaB) and
      proteolysis of IkappaB. All these effects were absent in animals receiving TNP
      470. Our results indicate that TNP-470 inhibits oxidative stress, nitric oxide
      production and NF-kappaB activation induced by experimental hepatocarcinogenesis.
      These changes would contribute to the beneficial effects of TNP-470 in cancer
      treatment.

PMID- 14567446
TI  - Action of DCFH and BODIPY as a probe for radical oxidation in hydrophilic and
      lipophilic domain.
AB  - Fluorogenic probes such as 2',7'-dichlorofluorescin (DCFH) have been extensively
      used to detect oxidative events and to measure antioxidant capacity. At the same
      time, however, the inherent drawbacks of these probes such as non-specificity
      towards oxidizing species have been pointed out. The present study was carried
      out to analyze the action and dynamics of 4, 4-difluoro-5-(4-phenyl-1,3
      butadienyl)-4-bora-3a,4a-diaza-s-indacene-3-undecanoic acid (BODIPY) and DCFH as
      a fluorescent probe in the free radical-mediated lipid peroxidation in
      homogeneous solution, aqueous suspensions of liposomal membranes and LDL and
      plasma. The rate constant for the reaction of BODIPY with peroxyl radicals was
      estimated as 6.0 x 10(3) M(-1) s(-1), which makes BODIPY kinetically an
      inefficient probe especially in the presence of potent radical-scavenging
      antioxidants such as tocopherols, but a convenient probe for lipid peroxidation.
      On the other hand, the reactivity of DCFH toward peroxyl radicals was as high as
      Trolox, a water-soluble analogue of alpha-tocopherol. Thus, DCFH is kinetically
      more favored probe than BODIPY and could scavenge the radicals within lipophilic
      domain as well as in aqueous phase. The partition coefficients for BODIPY and
      DCFH were obtained as 4.57 and 2.62, respectively. These results suggest that
      BODIPY may be used as an efficient probe for the free radical-mediated oxidation
      taking place in the lipophilic domain, especially after depletion of alpha
      tocopherol, while it may not be an efficient probe for detection of aqueous
      radicals.

PMID- 14567445
TI  - A free radical scavenger, edaravone, attenuates steatosis and cell death via
      reducing inflammatory cytokine production in rat acute liver injury.
AB  - BACKGROUND/AIMS: Reactive oxygen radicals play an important role in various forms
      of liver injury. In this study, we evaluated the efficacy of edaravone, a newly
      synthesized free radical scavenger, in its clinical dosage on an experimental
      model of acute liver injury in rats. METHODS: The clinical dose of edaravone (3
      mg/kg) was intravenously administered immediately and 3 h after intraperitoneal
      administration of carbon tetrachloride (CCl4) in rats. Histological evaluation
      including apoptosis and cytokine profiles were examined. RESULTS: Fatty
      degeneration and necrosis with marked elevation of serum alanine aminotransferase
      and lactate dehydrogenase levels developed after CCl4 administration were
      significantly reduced by edaravone. In addition, the apoptotic index assessed by
      TUNEL method was significantly lowered in the edaravone treated group. Serum and
      liver transcription levels of interleukin-6, tumor necrosis factor-alpha,
      interleukin-4, and interleukin-10 were increased following CCl4 administration,
      and they were attenuated by edaravone treatment. The formation of
      malondialdehyde, 4-hydroxynonenal adduct and one of the markers for oxidative DNA
      damage, 8-hydroxy-2'-deoxyguanosine, was also inhibited by edaravone treatment.
      CONCLUSION: Edaravone has a remarkable protective effect on acute liver injury
      caused by oxygen radicals through not only attenuating the membrane lipid
      peroxidation, but also inhibiting the production of inflammatory cytokines. We
      theorize that edaravone may have a clinical benefit in the treatment of various
      liver injuries.

PMID- 14567447
TI  - MutY is down-regulated by oxidative stress in E. coli.
AB  - In Escherichia coli, MutM (8-oxoG DNA glycosylase/lyase or Fpg protein), MutY
      (adenine DNA glycosylase) and MutT (8-oxodGTPase) function cooperatively to
      prevent mutation due to 7, 8-dihydro-8-oxoguanine (8-oxoG), a highly mutagenic
      oxidative DNA adduct. MutM activity has been demonstrated to be induced by
      oxidative stress. Its regulation is under the negative control of the global
      regulatory genes, fur, fnr and arcA. However, interestingly the presence of MutY
      increases the mutation frequency in mutT- background because of MutY removes
      adenine (A) from 8-oxoG:A which arises from the misincorporation of 8-oxoG
      against A during DNA replication. Accordingly we hypothesized that the response
      of MutY to oxidative stress is opposite to that of MutM and compared the
      regulation of MutY activity with MutM under various oxidative stimuli. Unlike
      MutM, MutY activity was reduced by oxidative stress. Its activity was reduced to
      30% of that of the control when E. coli was treated with paraquat (0.5mM) or H2O2
      (0.1 mM) and induced under anaerobic conditions to more than twice that observed
      under aerobic conditions. The reduced mRNA level of MutY coincided with its
      reduced activity by paraquat treatment. Also, the increased activity of MutY in
      anaerobic conditions was reduced further in E. coli strains with mutations in
      fur, fnr and arcA and the maximum reduction in activity was when all mutations
      were present in combination, indicating that MutY is under the positive control
      of these regulatory genes. Therefore, the down-regulation of MutY suggests that
      there has been complementary mechanism for its mutagenic activity under special
      conditions. Moreover, the efficacy of anti-mutagenic action should be enhanced by
      the reciprocal co-regulation of MutM.

PMID- 14567448
TI  - Catechins induce oxidative damage to cellular and isolated DNA through the
      generation of reactive oxygen species.
AB  - Green tea catechins have antimutagenic and anticarcinogenic activities. On the
      other hand, several epidemiological studies have indicated significant positive
      relationship between green tea consumption and cancer. Catechins enhance colon
      carcinogenesis in rats initiated with chemical carcinogen. To clarify the
      mechanism underlying the potential carcinogenicity, we investigated the DNA
      damaging ability of catechins in human cultured cells. Catechin increased the
      formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), a characteristic
      oxidative DNA lesion, in human leukemia cell line HL-60 but not in HP100, a
      hydrogen peroxide (H2O2)-resistant cell line derived from HL-60. The catechin
      induced formation of 8-oxodG in HL-60 cells significantly decreased by
      bathocuproine. Furthermore, we investigated DNA damage and its site-specificity
      induced by catechins, using 32P-labeled DNA fragments. Catechin and epicatechin
      induced extensive DNA damage in the presence of Cu(II). Catechin caused
      piperidine-labile sites at thymine and cytosine residues in the presence of
      Cu(II). Catalase and bathocuproine inhibited the DNA damage, indicating the
      involvement of H2O2 and Cu(I). NADH enhanced catechins plus Cu(II)-induced 8
      oxodG formation in calf thymus DNA, suggesting the redox cycle between catechins
      and their corresponding quinones, the oxidized forms of catechins. The DNA
      damaging ability of epicatechin is stronger than that of catechin, possibly due
      to the greater turnover frequency of the redox cycle. The difference in their
      redox properties could be explained by their redox potentials estimated form an
      ab initio molecular orbital calculation. The present study demonstrated that
      catechins could induce metal-dependent H2O2 generation during the redox reactions
      and subsequently damage to cellular and isolated DNA. Therefore, it is reasonably
      considered that green tea catechins may have the dual function of
      anticarcinogenic and carcinogenic potentials.

PMID- 14567449
TI  - Protective effects of anthocyanins from blackberry in a rat model of acute lung
      inflammation.
AB  - Anthocyanins are a group of naturally occuring phenolic compounds related to the
      coloring of plants, flowers and fruits. These pigments are important as quality
      indicators, as chemotaxonomic markers and for their antioxidant activities. Here,
      we have investigated the therapeutic efficacy of anthocyanins contained in
      blackberry extract (cyanidin-3-O-glucoside represents about 80% of the total
      anthocyanin contents) in an experimental model of lung inflammation induced by
      carrageenan in rats. Injection of carrageenan into the pleural cavity elicited an
      acute inflammatory response characterized by fluid accumulation which contained a
      large number of neutrophils as well as an infiltration of polymorphonuclear
      leukocytes in lung tissues and subsequent lipid peroxidation, and increased
      production of nitrite/nitrate (NOx) and prostaglandin E2 (PGE2). All parameters
      of inflammation were attenuated in a dose-dependent manner by anthocyanins (10,
      30 mg kg(-1) 30 min before carrageenan). Furthermore, carrageenan induced an
      upregulation of the adhesion molecule ICAM-1, nitrotyrosine and poly (ADP-ribose)
      synthetase (PARS) as determined by immunohistochemical analysis of lung tissues.
      The degree of staining was lowered by anthocyanins treatment. Thus, the
      anthocyanins contained in the blackberry extract exert multiple protective
      effects in carrageenan-induced pleurisy.

PMID- 14567450
TI  - Vitamin C (ascorbic acid) induced hydroxyl radical formation in copper
      contaminated household drinking water: role of bicarbonate concentration.
AB  - We have previously shown that Vitamin C (ascorbic acid) can trigger hydroxyl
      radical formation in copper contaminated household drinking water. We report here
      that the capacity of ascorbic acid to catalyze hydroxyl radical generation in the
      drinking water samples is strongly dependent on the bicarbonate concentration
      (buffer capacity and pH) of the samples. We found that at least 50 mg/l
      bicarbonate was required in the water samples to maintain the pH over 5.0 after
      ascorbic acid addition. At this pH, that is higher than the pKa1 4.25 of ascorbic
      acid, a hydroxyl radical generating redox cycling reaction involving the mono
      anion of vitamin C and copper could take place. The ascorbic acid induced
      hydroxyl radical generating reaction could easily be mimicked in Milli-Q water by
      supplementing the water with copper and bicarbonate. Our results demonstrate that
      ascorbic acid can induce a pH dependent hydroxyl radical generating reaction in
      copper contaminated household tap water that is buffered with bicarbonate. The
      impact of consuming ascorbic acid together with copper and bicarbonate containing
      drinking water on human health is discussed.

PMID- 14567451
TI  - Measuring physician performance: enhancing quality of care, reducing costs.

PMID- 14567452
TI  - Mass customization--the next generation of pharmacy management.

PMID- 14567453
TI  - Usual and unusual causes of duodenal ulcer.

PMID- 14567454
TI  - Treatment options for patients with Helicobacter pylori infection resistant to
      one or more eradication attempts.
AB  - Proton pump inhibitor-based triple regimens fail to cure Helicobacter pylori
      infection in at least 10-23% of treated patients. Re-treatment strategies after
      initial failure remain poorly defined. Of the factors leading to eradication
      failure, patients' compliance, gender, primary resistance to clarithromycin and
      metronidazole, and intragastric bacterial load appear to be the most important in
      determining treatment outcome. Empirical re-treatment should depend mainly upon
      the antibiotics initially used, as re-administration of the same compound
      (namely, metronidazole and clarithromycin) is not recommended. Quadruple therapy
      is usually suggested in this situation, but there is some reluctance to use it in
      clinical practice on account of the high number of tablets to be taken and
      concern about side-effects. The use of ranitidine bismuth citrate instead of a
      proton pump inhibitor plus a bismuth compound in triple second-line regimens has
      recently proven to be highly effective. Finally, rifabutin-based triple therapies
      have been shown to be a promising rescue strategy in patients who have failed two
      or more eradication attempts.

PMID- 14567455
TI  - History in our lifetime: the changing nature of refractory duodenal ulcer in the
      era of histamine H2 receptor antagonists.
AB  - BACKGROUND AND AIM: This prospective cohort observational study, set in a
      district hospital, presents our experience (1976-1993) of duodenal ulcer
      refractory to histamine H2 receptor antagonists (defined as not healed after 3
      months' treatment) and comments on onset, outcome and spontaneous decline.
      METHODS: Patients were treated mainly with cimetidine, the dose being titrated
      (up to 3.2 g daily) according to response, and followed by serial check endoscopy
      and clinical assessment. RESULTS: A total of 782 of the 4032 duodenal ulcer
      patients seen (19%) were refractory; the incidence declined over time: 1976-1978:
      124/379 (33%); 1979-1983: 390/1240 (31%); 1984-1988: 190/1295 (15%); 1989-1993:
      78/1118 (7%). A total of 344 were refractory for the first time on their first
      healing course and 174 on their second. Healing was achieved in two-thirds after
      a mean of 7 months' treatment with cimetidine 1 g; treatment for 12-18 months
      with higher doses was needed in the remainder. Relapse occurred in up to three
      quarters of patients despite maintenance cimetidine up to 3 g daily. Eventually
      47 patients were operated upon but good results (i.e., no ulcer, no symptoms)
      were achieved in only 11. CONCLUSION: Refractoriness was common until recently.
      Its incidence has declined dramatically, the fall preceding the newer more
      powerful treatment with proton pump inhibitors and with Helicobacter pylori
      eradication. We suggest this phenomenon is a modern example of a spontaneous
      change in the natural history of the disease.

PMID- 14567456
TI  - Contribution of the gastrointestinal tract below the stomach to the 13C-urea
      breath test.
AB  - BACKGROUND: Graham et al. [Lancet, I (1987) 1174] found a late increase of 13C
      enrichment in the 13C-urea breath test 120 min after administration of labeled
      urea to patients without Helicobacter pylori infection. This may give false
      positive results. AIM: We designed this study to elucidate the contribution of
      the gastrointestinal tract below the stomach to the 13C-urea breath test.
      PATIENTS: Twenty-eight patients with dyspeptic symptoms who gave their consent
      were enrolled. METHODS: Patients underwent the 13C-urea breath tests both via the
      mouth (as usual) and the duodenum (labeled urea introduced to the second
      portion). Breath samples were collected at baseline, 5, 15, 30, 45, 60, 90, 120,
      150 and 180 min for analysis. H. pylori status was defined by the CLOtest and by
      histological examination. RESULTS: There was no late increase in 13C enrichment
      of 13C-urea breath test for eight H. pylori negative patients either via the
      mouth or the duodenum. For those H. pylori positive patients, seventeen had no
      late rise 13C enrichment of the 13C-urea breath test via the duodenum and three
      patients had a rise after 15 min. CONCLUSIONS: No late rise in 13CO2 excretion to
      cause a positive 13C-urea breath test up to 180 min after the administration of
      labeled urea was found in the present study.

PMID- 14567457
TI  - Primary and secondary antibiotic resistance of Helicobacter pylori strains
      isolated in central Italy during the years 1998-2002.
AB  - BACKGROUND: Antibiotic resistance of Helicobacter pylori is the most common
      reason for failure in its eradication. AIM: To determine the incidence of primary
      and secondary resistance to tinidazole, clarithromycin and amoxycillin in
      Helicobacter pylori isolates from dyspeptic patients in central Italy and to
      evaluate the modifications of resistance over the period from 1998 to 2002.
      METHODS: H. pylori strains were isolated from antral biopsies taken during upper
      endoscopy in 406 dyspeptic patients with no previous therapy against H. pylori,
      and in 96 patients who had already undergone one or more triple therapies.
      Antibiotic susceptibility test was performed using the screening agar method and
      agar dilution method. RESULTS: Overall primary resistance to tinidazole,
      clarithromycin and amoxycillin was 36.7, 23.4 and 0.2%, respectively. Secondary
      resistance rates were: tinidazole 69.8%, clarithromycin 82.3% and amoxycillin 1%.
      Resistance to clarithromycin was often associated with tinidazole resistance and
      was significantly higher in female patients (p<0.05). Primary and secondary
      antibiotic resistance did not change during the 4 years of observation.
      CONCLUSIONS: The dyspeptic population with H. pylori infection in central Italy
      shows high levels of antibiotic resistance. Primary resistance to clarithromycin
      is most frequent in female patients. In patients with secondary resistance, dual
      resistance to clarithromycin and tinidazole is found in the majority of cases.

PMID- 14567458
TI  - Combination immunomodulatory therapy with cyclosporine and azathioprine in
      corticosteroid-resistant severe ulcerative colitis: the Edinburgh experience of
      outcome.
AB  - BACKGROUND: Cyclosporine is a fungal metabolite and a powerful immunosuppressant.
      While response to intravenous steroids in severe ulcerative colitis is in excess
      of 60%, the remainder of patients are left with the options of curative
      panproctocolectomy or administration of intravenous rescue therapy with
      cyclosporine. There have been conflicting reports on the efficacy of intravenous
      cyclosporine in acute ulcerative colitis, and there are serious concerns about
      potential toxicity and opportunistic infections such as Pneumocystis carnii
      pneumonia. There are also concerns about early relapse and colectomy following
      cyclosporine rescue. To date there has been a paucity of data available to help
      guide the gastroenterologist in the use of cyclosporine and the maintenance of
      remission once achieved. METHODS: Between 1994 and 2001, a total of sixteen
      patients who had received intravenous cyclosporine for acute exacerbation of
      their known UC (seven females, nine males, mean age 33 years) whose records were
      available for analysis. All patients were refractory to intravenous
      methylprednisolone (60 mg/24 h). Patients who responded to cyclosporine were
      discharged on a regimen of oral cyclosporine, oral steroids oral azathioprine and
      5-aminosalicylate. RESULTS: Median disease duration was 5.4 years (range 0.9-25
      years). All sixteen patients were initially treated with cyclosporine at a dose
      of 4 mg/kg/day. Nine patients were started on oral azathioprine (median dose 1.8
      mg/kg). Seven patients underwent surgery (panproctocolectomy), although none had
      surgery after 6 months. Comparisons were made between patients with <7 days and
      >7 days intravenous steroid. Other parameters analysed were stool frequency at 3
      days and CRP at 3 days. There were no significant differences between these
      groups. Median bowel frequency at day 3 was higher in patients who finally
      underwent surgery. At 3 years follow-up, 56% of the sixteen patients had avoided
      surgery by using azathioprine immunosuppression. CONCLUSION: The initial response
      rate to intravenous cyclosporine was high (69%). Side effects were documented in
      the majority of patients, but none of the patients had to discontinue treatment
      on account of these. Azathioprine has a useful role in maintaining the remission
      achieved by i.v. cyclosporine for acute ulcerative colitis patients. More than
      half the patients will avoid colectomy long-term when using triple
      immunosuppressive therapy including azathioprine adding support for its relative
      safety and another role for its use.

PMID- 14567459
TI  - Are colonic regular contractile frequency patterns in slow transit constipation a
      relevant pathophysiological phenomenon?
AB  - BACKGROUND: Pathogenesis of slow transit constipation still remains elusive. Some
      studies have shown several colonic motor abnormalities; however, it is not easy
      to understand the relative importance of the single ones. AIMS: Since it has been
      hypothesized that an excess of periodic distal motor activity may be of
      pathophysiological importance in patients with slow transit constipation, we
      evaluated regular colonic contractile frequencies in a homogeneous cohort of
      these patients. PATIENTS: A total of 26 female patients (age range 34 to 67
      years) fulfilling the Rome II criteria for constipation entered the study. No
      patient had evidence of secondary forms of constipation and distal obstruction.
      METHODS: Twenty-four hour colonic manometric studies were obtained for each
      patient. Regular contractile patterns (with frequencies ranging from 2 to 8
      cycles/min) were calculated for the entire recording period and in single colonic
      segments. RESULTS: Overall, regular patterns accounted for about 3% of the total
      colonic motor activity (average 30 min/day per subject), with the 3 cycles/min
      being the predominant contractile rhythm. Most of this activity was present in
      the sigmoid colon, accounting for >50% of the total amount of motility, and it
      was more prevalent than in the descending and transverse colon; no differences
      were revealed in the descending with respect to the transverse colon. No daily
      fluctuations of regular contractile activity, nor a cyclic pattern, nor migration
      between recording points were observed. CONCLUSIONS: Regular colonic frequency
      patterns are probably of minor pathophysiological importance in slow transit
      constipation, even in the light of the scant amount of such phenomena previously
      documented in healthy subjects.

PMID- 14567460
TI  - Molecular mechanisms involved in the antiproliferative effect of two COX-2
      inhibitors, nimesulide and NS-398, on colorectal cancer cell lines.
AB  - BACKGROUND: Cyclooxygenase (COX)-2 is up-regulated in most colorectal cancers.
      Chronic use of non-steroidal anti-inflammatory drugs, which target
      cyclooxygenases, have been shown to reduce the risk of these cancers. However,
      the mechanisms underlying this protective effect remain unclear. AIMS: The aim of
      our study was to characterize the effects of two COX-2 selective inhibitors, NS
      398 and nimesulide, on colorectal cancer cell proliferation, and to describe the
      molecular mechanisms involved. MATERIALS AND METHODS: HT-29 and SW-1116 cell
      lines were cultured with either NS-398 or nimesulide. Cell proliferation was
      assessed by staining DNA with crystal violet. Cell cycle repartition and
      apoptosis were analysed by flow cytometry. The expression of COX-1 and COX-2. and
      of two cyclin dependent kinase inhibitors, p21Cip1 and p27Kip1, was analysed by
      Western blotting and RT-PCR. RESULTS: Both drugs dose-dependently inhibited cell
      proliferation and induced G1 cell cycle blockade. HT-29 cells were more sensitive
      to both drugs than SW-1116 cells. p21Cip1 and p27Kip1 were induced on both cell
      lines. Concomitant induction of p21Cip1 mRNA indicates transcriptional
      modulation, whereas induction of p27Kip1 only at the protein level suggests post
      translational modulation. CONCLUSION: NS-398 and nimesulide inhibit colorectal
      cell proliferation through induction of p21Cip1 and p27Kip1.

PMID- 14567461
TI  - Helicobacter pylori diagnosis in patients with liver cirrhosis.
AB  - BACKGROUND: In cirrhotics, Helicobacter pylori infection is the major cause of
      peptic lesions, which are an important cause of upper intestinal haemorrhage in
      these patients. However, some diagnostic methods are not accurate for H. pylori
      detection in cirrhotics. AIMS: The study assessed the accuracy of different
      diagnostic methods for H. pylori detection in cirrhotics with and without
      gastroduodenal lesions. METHODS: The study population comprised of 53 cirrhotics.
      All patients underwent upper endoscopy: three biopsies were taken in the antrum
      and three in the gastric body. Four biopsies were used for Giemsa staining, while
      two were used for a rapid urease test. A blood sample was obtained for serology
      using Western blotting, and a [13C]urea breath test was performed in all
      patients. Histological assessment was regarded as the gold standard for diagnosis
      of H. pylori infection. RESULTS: H. pylori infection was detected at histological
      assessment in 28 (52.8%) patients. The [13C]urea breath test, rapid urease test,
      and serology were positive in 27 (51%) patients, 23 (43.4%) patients, and 34
      (64.1%) patients, respectively. Sensitivity and specificity were 92.9 and 96% for
      the [13C]urea breath test, 78.6 and 96% for the rapid urease test, and 78.6 and
      52% for serology. CONCLUSIONS: The [13C]urea breath test is very accurate in
      cirrhotics, whilst both serology and the rapid urease test give disappointing
      results.

PMID- 14567462
TI  - Novel association of HLA-haplotypes with primary sclerosing cholangitis (PSC) in
      a southern European population.
AB  - AIMS: In patients with with primary sclerosing cholangitis we investigated the
      major histocompatibility complex (MHC) genes and mutations of the cystic fibrosis
      transmembrane conductance regulator (CFTR) gene. METHODS: In 64 PSC patients and
      183 normal controls of the same population (Northern Italy), allelic
      polymorphisms at the DNA level were investigated in MHC region genes: HLA-DRB1,
      HLA-DQB1 and HLA-B, tumour necrosis factor A (TNFA), and in CFTR gene, with
      polymerase chain reaction-based methodologies. RESULTS: Frequencies of DRB1*01,
      DQA1*0101, DQB1*0102 (14 vs. 8%, p<0.05), DRB1*16, DQA1*0102, DQB1*0502 (8 vs.
      3%, p<0.025) and DRB1*04, DQA1*03, DQB1*0301 (10 vs. 4%, p<0.005) haplotypes were
      more elevated in PSC patients. The frequency of patients positive for HLA
      DRB1*01, *1601 or *04 related haplotypes was significantly increased (32 vs. 14%,
      p<0.00025). DRB1*07, DQA1*0201, DQB1*02 haplotype frequency was significantly
      decreased (4 vs. 15%, p<0.001). After removing HLA-DRB1*01, *1601, *04 related
      haplotype sharing patients, HLA-DRB1*03, DQA1*0501, DQB1*02 haplotype frequency
      was significantly increased (32 vs. 14%, p<0.01). TNFA2 allele frequency was
      significantly increased in PSC patients (23 vs. 14%, p<0.025), as well as the
      TNFA2 homozygous genotype (9 vs. 0.5%, p=0.0013). No mutations were found on the
      CFTR gene and the allelic frequency of the 5T polymorphism in intron 8 was not
      increased. CONCLUSION: These data suggest that the role of genes in the HLA
      region is relevant, but not necessarily disease-specific and it might be
      different in populations with divergent ancestries.

PMID- 14567463
TI  - Unsuspected ileal stenosis causing obscure GI bleeding in patients with previous
      abdominal surgery--diagnosis by capsule endoscopy: a report of two cases.
AB  - Peri-anastomotic ulcerations may occur in patients with previous abdominal
      surgery. They may present only with obscure GI bleeding. We report two cases in
      whom capsule endoscopy identified postsurgical stenoses with ulcers as the cause
      of obscure GI bleeding. Case 1. A 57-year-old male operated on in 1970 for a post
      traumatic diaphragm hernia followed by displacement of the caecum in the upper
      left abdominal quadrant. Case 2. A 32-year-old female with a salpingectomy for
      tuberculosis (1978) followed by segmental ileal resection for intestinal
      obstruction. Both patients had undergone extensive work-up including
      bidirectional endoscopies and enteroclysis with negative results. Capsule
      endoscopy with the GIVEN diagnostic system was done. Ileal stenoses with mucosal
      ulcers in dilated prestenotic loops were observed in both cases. The capsule was
      retained at the stenosis site, requiring ileal resection and anastomosis.
      Pathology reports showed mucosal ulcers. In case 2, tuberculosis was ruled out by
      tissue and faecal polymerase chain reaction and culture. Ileal stenoses with
      prestenotic ulcerations causing GI bleeding may occur in patients with previous
      abdominal surgery. Capsule endoscopy may clarify the diagnosis and shorten the
      diagnostic work-up. However, these patients should be warned that capsule
      retention requiring surgery might occur.

PMID- 14567464
TI  - Co-existence of hyperparathyroidism, hypergastrinaemia and multiple gastric
      carcinoids is not always due to incomplete expression of the MEN-1 syndrome.
AB  - Until recently, the association of primary hyperparathyroidism and gastric
      carcinoid, with or without hypergastrinaemia, had been considered an incomplete
      form of multiple endocrine neoplasia type 1. This is because it seemed unlikely
      that the rare joint appearance of these diseases could occur only by chance. It
      is now possible to evaluate the pathogenetic involvement of the multiple
      endocrine neoplasia type 1 gene in many, apparently sporadic, clinical
      conditions. This is a case report of a female mimicking multiple endocrine
      neoplasia type 1 due to the presence of hyperparathyroidism, gastric carcinoid,
      and hypergastrinaemia. However, involvement of the MEN-1 gene (exons 2-10) was
      not detected, whereas hypergastrinaemia was attributed to a chronic atrophic
      gastritis.

PMID- 14567465
TI  - Review of the implications of dietary tryptophan intake in patients with
      irritable bowel syndrome and psychiatric disorders.
AB  - In this review, we address the possible role of the essential amino acid L
      tryptophan or its metabolic derivative 5-hydroxytryptophan in the modulation of
      serotonin (5-hydroxytryptamine) synthesis and thereby in affecting the
      pathophysiology of central and peripheral nervous system disorders, including
      depression and irritable bowel syndrome. L-Tryptophan may represent a link
      between apparently disparate functional disorders and is of interest for general
      gastroenterologists, neurogastroenterologists, and neurologists. On the basis of
      estimates showing that approximately 20% of patients with functional bowel
      disorders seeking care in referral centres have psychiatric comorbidity, we
      attempt to provide a conceptual framework for defining the possible role of L
      tryptophan in this population.

PMID- 14567466
TI  - TNFalpha promoter polymorphisms in Italian patients with porphyria cutanea tarda.

PMID- 14567467
TI  - Impact of uncoupling protein-2 expression on the prognosis of gastric
      adenocarcinoma patients.

PMID- 14567468
TI  - Oral tryptophan challenge studies in cirrhotic patients: no evidence of
      neuropsychiatric changes.
AB  - Hepatic encephalopathy is a frequent complication of cirrhosis. Abnormalities of
      5-hydroxytryptamine (5-HT) and its metabolites are recognized and may contribute
      to its pathogenesis. We therefore studied the effect of an oral tryptophan load
      (6-18 g) upon psychometric test scores and analyzed EEG's in alcoholic cirrhotic
      patients. Eight patients had had previous encephalopathic episodes related to
      variceal bleeds and one patient was awaiting a liver transplant. Five out of the
      10 patients had at least one abnormal baseline psychometric test. Following
      tryptophan challenge there were no changes in blood ammonia but plasma tryptophan
      levels were elevated approximately 10-fold (p < 0.01 x 10(-7)). Nevertheless,
      there were no statistically significant changes in psychometric testing or
      analyzed EEG frequency distribution. All patients reported nausea or vomiting
      while one patient developed a short-lived serotonin like syndrome. We conclude
      that in this group of patients, an oral tryptophan load does not induce or worsen
      subclinical hepatic encephalopathy. If the high blood levels of tryptophan seen
      in these studies are able to influence cerebral neurotransmitter synthesis, the
      results do not support a primary role for abnormalities of 5-HT neurotransmission
      in hepatic encephalopathy.

PMID- 14567469
TI  - Homocysteine inhibits butyrylcholinesterase activity in rat serum.
AB  - In the present work we investigated the in vitro effects of homocysteine (Hcy)
      and methionine (Met), metabolites accumulated in homocystinuria, on
      butyrylcholinesterase (BuChE) activity in rat serum. We also studied the kinetics
      of the inhibition of BuChE activity caused by Hcy. For determination of BuChE we
      used serum of 60-day-old Wistar rats, which was incubated in the absence
      (control) or presence of Hcy (0.01-0.5 mM) or Met (0.2-2.0 mM). The kinetics of
      the interaction of Hcy and BuChE was determined using the Lineweaver-Burk double
      reciprocal plot. Results showed that serum BuChE activity was not altered by Met,
      but it was significantly inhibited (37%) by 500 microM Hcy, a concentration
      similar to those found in blood of homocystinuric patients. The apparent Km
      values, in the absence and presence of 500 microM of Hcy, were 0.034 and 0.142
      mM, respectively, and V(max) of BuChE for acetylcholine (ACh) as substrate was
      1.25 micromol ACSCh/h/mg of protein. The Ki value obtained was 120 microM, and
      the inhibition was of the competitive type, suggesting a common binding site for
      Hcy and ACh. It is proposed that inhibition of cholinesterase activity may be one
      of the mechanisms involved in the neurological dysfunction observed in
      homocystinuria.

PMID- 14567470
TI  - Changing metabolic and energy profiles in fetal, neonatal, and adult rat brain.
AB  - The regional energy status and the availability of metabolic substrates during
      brain development are important, since a variety of fetal metabolic insults have
      been increasingly implicated in the evolution of neonatal brain disorders. The
      response of the brain to a metabolic insult is determined, in large part, by the
      ability to utilize the various substrates for intermediary metabolism in order to
      maintain energy stores within the tissue. To ascertain if metabolic conditions of
      the fetal brain make it more or less vulnerable to a stress, the high-energy
      phosphates and glucose-related compounds were examined in five regions of the
      embryonic day 18 (E-18) fetal brain. Glucose and glycogen levels in the E-18
      fetal brain were generally higher in the cerebellum and its neuroepithelium than
      in the hippocampus, cerebral cortex, and its neuroepithelium. Regional lactate
      and high-energy phosphate concentrations were essentially the same in the five
      regions. Subsequently, the metabolic profile was examined in the cerebral cortex
      and striatum from E-18, postpartum day 7 (P-7) and adult rats. At the various
      stages of development, there were only minimal differences in the high-energy
      phosphate levels in the striatum and cortex. Glucose levels, the primary
      substrate in the adult brain, were essentially unchanged throughout development.
      In contrast, lactate was significantly elevated by 6- and 2-fold over those in
      the adult brain in the E-18 and P-7 striatum and cortex, respectively. Another
      alternative substrate, beta-hydroxybutyrate, was also significantly elevated at E
      18 and increased more than 2-fold at P-7, but was barely detectable in the adult
      cortex and striatum. Finally, glucose and lactate levels were examined in
      cerebrospinal fluid, blood, and brain from the E-18 brain to determine if a
      gradient among the compartments exists. The levels of both lactate and glucose
      exhibited a concentration gradient in the E-18 fetus: blood > cerebrospinal fluid
      > brain parenchyma. The results indicate that energy state in the fetal brain is
      comparable to that in the neonates and the adults, but that the availability of
      alternative substrates for intermediary metabolism change markedly with
      development. The age-dependent substrate specificity for intermediary metabolism
      could affect the response of the fetal brain to a metabolic insult.

PMID- 14567472
TI  - L-cysteine increases glucose uptake in mouse soleus muscle and SH-SY5Y cells.
AB  - Previous investigation demonstrated the potential of L-cysteine (L-Cys) at high
      concentrations to cause hypoglycemia in mice totally deprived of insulin. For
      further elucidation of the glucose-lowering mechanism, glucose uptake and
      quantity of glucose transporters (GLUTs 3 and 4) in mouse soleus muscle and C2C12
      muscle cells, as well as in human SH-SY5Y neuroblastoma cells, were investigated.
      A marked enhancement of glucose uptake was demonstrated, peaking at 5.0 mM L-Cys
      in soleus muscle (P < 0.05) and SH-SY5Y cells (P < 0.001), respectively. In
      contrast, glucose uptake was not affected in the C2C12 muscle cells. Kinetic
      analysis of the SH-SY5Y glucose uptake showed a 2.5-fold increase in maximum
      transport velocity compared with controls (P < 0.001). In addition, both GLUT3
      and GLUT4 levels were increased following exposure to L-Cys. Our findings point
      to a possible hypoglycemic effect of L-Cys.

PMID- 14567471
TI  - Effect of propionic and methylmalonic acids on the in vitro phosphorylation of
      intermediate filaments from cerebral cortex of rats during development.
AB  - In this study we investigated the in vivo and in vitro effects of methylmalonic
      (MMA) and propionic acids (PA), at concentrations usually found in methylmalonic
      acidemia and propionic acidemia respectively, on the phosphorylation of
      intermediate filament proteins in cerebral cortex of rats during development.
      Rats of 9, 12, and 17 days were acutely injected with the acids and sacrificed 90
      min after injection. The cerebral cortex was dissected, and slices were incubated
      with 32P-orthophosphate. The cytoskeletal fraction was extracted and the
      radioactivity incorporated into intermediate filament subunits was measured. In
      addition, cortical slices from nontreated rats of 9, 12, 15, 17, 21, and 60 days
      of life were incubated with the acids in the presence of 32P-orthophosphate, the
      cytoskeletal fraction was extracted and the radioactivity was measured. Results
      demonstrated that MMA and PA significantly decreased the radioactivity
      incorporated into intermediate filament proteins at day 12, both in vivo and in
      tissue slices. In contrast, PA increased the in vitro phosphorylation of the
      cytoskeletal proteins in slices of 21-day-old animals. It acts through PP2A and
      PP2B in 12-day-old rats and through PKA and PKCaMII in 21-day-old animals. We
      propose that alteration of cytoskeletal protein phosphorylation caused by
      methylmalonic and propionic acids may be related to the neurological dysfunction
      characteristic of propionic and methylmalonic acidemia.

PMID- 14567473
TI  - Effects of L-2-hydroxyglutaric acid on various parameters of the glutamatergic
      system in cerebral cortex of rats.
AB  - L-2-Hydroxyglutaric acid (LGA) accumulates and is the biochemical hallmark of the
      neurometabolic disorder L-2-hydroxyglutaric aciduria (LHGA). Although this
      disease is predominantly characterized by severe neurological findings and
      pronounced cerebral atrophy, the pathomechanisms of brain injury are virtually
      unknown. In the present study, we investigated the effect of LGA (0.1-1 mM) on
      various parameters of the glutamatergic system, namely the basal and potassium
      induced release of L-[3H]glutamate by synaptosomal preparations, Na(+)-dependent
      L-[3H]glutamate uptake by synaptosomal preparations and Na(+)-independent L
      [3H]glutamate uptake by synaptic vesicles, as well as of L-[3H]glutamate binding
      to synaptic plasma membranes from cerebral cortex of male adult Wistar rats. We
      observed that LGA significantly increased L-[3H]glutamate uptake into
      synaptosomes and synaptic vesicles, without altering synaptosomal glutamate
      release and glutamate binding to synaptic plasma membranes. Although more
      comprehensive studies are necessary to evaluate the exact role of LGA on
      neurotransmission, our findings do not support a direct excitotoxic action for
      LGA. Therefore, other abnormalities should be searched for to explain
      neurodegeneration of LHGA.

PMID- 14567474
TI  - Bioethics in a multicultural world: medicine and morality in pluralistic
      settings.
AB  - Current approaches in bioethics largely overlook the multicultural social
      environment within which most contemporary ethical issues unfold. For example,
      principlists argue that the "common morality" of "society" supports four basic
      ethical principles. These principles, and the common morality more generally, are
      supposed to be a matter of shared "common sense." Defenders of case-based
      approaches to moral reasoning similarly assume that moral reasoning proceeds on
      the basis of common moral intuitions. Both of these approaches fail to recognize
      the existence of multiple cultural and religious traditions in contemporary
      multicultural societies. In multicultural settings, patients and their families
      bring many different cultural models of morality, health, illness, healing, and
      kinship to clinical encounters. Religious convictions and cultural norms play
      significant roles in the framing of moral issues. At present, mainstream
      bioethics fails to attend to the particular moral worlds of patients and their
      family members. A more anthropologically informed understanding of the ethical
      issues that emerge within health care facilities will need to better recognize
      the role of culture and religion in shaping modes of moral deliberation.

PMID- 14567475
TI  - Patenting human genes: when economic interests trump logic and ethics.
AB  - To date, over 5,000 applications have been filed with United States Patent Office
      for patents on human genes. More than 1,500 of these applications have been
      granted. Other jurisdictions are experiencing a similar rush to mine and protect
      genomic gold. This paper argues that although many jurisdictions allow the
      patenting of human genes, this is ethically indefensible and amounts to an
      unjustified appropriation of a general human heritage. Economic and legal
      arguments in favour of patenting are considered and rejected. Reference is made
      to the Wellcome Trust Consortium's initiative and the Merck Gene Index Project,
      which place patented genetic information into the public domain.

PMID- 14567476
TI  - Can the four principles help in genetic screening decision-making?
AB  - Although principles, as a framework to resolving moral dilemmas are still debated
      and seem to be in a philosophical quagmire, there are strong arguments that by
      specification one can resolve case-specific dilemmas in certain areas of
      bioethics. When it comes to genetic screening and testing however, the problem at
      the base is a moral disagreement on higher-order principles--such as the status
      of the embryo and parental issues. No amount of specification can resolve these
      issues without a dose of relativism. We explore a possibility of agreement on
      debatable areas specifically in regard to genetics--such as conferring status to
      the embryo solely for purposes of preventing genetic selection; but it is
      difficult to see how this can be incorporated into law without extrapolation to
      other areas. We conclude therefore that the four-principles approach, albeit
      valuable for expounding opposing views and discussing issues, cannot either alone
      or by specification, help resolve issues of genetic screening and testing without
      agreeing on higher order principle. This does not seem to be a possibility in the
      near future.

PMID- 14567477
TI  - Voice beyond choice: hesitant voice in public debates about genetics in health
      care.
AB  - The rise of genetic techniques presents a great promise as well as some difficult
      dilemma's about how genetics will affect the way we will be able to live our
      lives. For this reason, in many countries, public debates are organized to
      reflect upon the development of predictive medicine. In this essay we focus on
      economist A. Hirschman's work on "exit, voice and loyalty" to analyse and enrich
      these public debates. We first introduce Hirschman's triad of concepts and focus
      on the concept of "voice," which refers to an institution's ability to allow
      clients to give feedback about products or services, and its ability to listen to
      the feedback given. We argue that voice is particularly important for the health
      care system in which predictive medicine is developing. Voice is crucial because
      how predictive medicine will become institutionalised is now in the process of
      becoming determined. However, in public debates about predictive medicine, voice
      tends to be reduced to providing people with the option of making a choice
      whether to use genetic techniques or not. We argue that this reduction of voice
      to choice is not very informative about predictive medicine and suggest an
      amendment of Hirschman's concept of voice, which we call "hesitant voice."
      Hesitant voice attempts to be informative about the uncertainty people experience
      in addressing predictive medicine and topicalises the gradual, the embodied, the
      tentative character of voice in developing situations like that of predictive
      medicine.

PMID- 14567478
TI  - The ethics of public consultation in health care: an Orthodox Jewish perspective.
AB  - New Zealand and United Kingdom governments have set new directives for increased
      consultation with the public about health care. Set against a legacy of modest
      success with past engagement with public consultations, this paper considers
      potentially adverse ethical implications of the new directives. Drawing on
      experiences from New Zealand and the United Kingdom, and on an Orthodox Jewish
      perspective, the paper seeks to answer two questions: What conditions can
      compromise the ethics of public consultation? How can the public respond
      ethically to consultation? In answering these questions, the paper considers how
      Orthodox Judaism, as a specific positive morality, can aid the development of
      public policy. It is suggested that an Orthodox Jewish perspective does not
      require limiting the content of public consultations and helps to define a common
      procedural morality binding Jews and non-Jews. This procedural morality requires
      avoiding two conditions that, as shown from Jewish texts, make public
      consultation unethical. These are "overpreparation" and "underpreparation."
      Members of the public who deem a consultation unethical should give feedback not
      on the proposal but on the conditions they perceive to prevent the consulting
      party from considering their viewpoints on the proposal.

PMID- 14567479
TI  - The significance of the goal of health care for the setting of priorities.
AB  - The purpose of the article is to argue for the significance of a clarified goal
      of health care for the setting of priorities. Three arguments are explored.
      First, assessment of needs becomes necessary in so far as the principle of need
      should guide the priority-setting. The concept of health care need includes a
      goal component. This component should for rational reasons be identical with the
      goal of health care. Second, in order to use resources efficiently it is
      necessary to assess the effects of health care. It is not, however, a question of
      assessing whether there is an effect but a question of assessing whether there is
      the right effect. And what constitutes the right effect can only be determined in
      relation to the goal of the enterprise. Third, the health sector involves several
      groups of actors such as politicians, administrators, doctors, nurses,
      physiotherapists, occupational therapists, educationists and patients. It is
      common knowledge that successful teamwork requires an understanding of a common
      goal. The article ends with an example of a goal chosen from ethics.

PMID- 14567480
TI  - Education, practice and bioethics: growing barriers to ethical practice.
AB  - While Bioethics is now taught at all medical colleges in the United States as
      well as in other nations, and while discussions about Bioethics have become
      frequent in most medical journals there are increasing barriers to teaching and
      incorporating what has been taught into daily practice. I shall discuss some of
      these barriers and suggest that integrating the teaching of Bioethics throughout
      the curriculum after presenting some of the basic theory and methodology is the
      most effective way of teaching this vital subject. Furthermore, courses in health
      care ethics are often taught as something distinct and distinguishable from one's
      medical practice. I shall emphasize what I consider to be the failure of
      Bioethics to participate effectively in creating a context whereby what has been
      taught can be put into praxis. In this brief article I will discuss such barriers
      and suggest several approaches and remedies.

PMID- 14567481
TI  - Common causes of night sweats in various populations.

PMID- 14567482
TI  - Diagnosing night sweats requires clear definition.

PMID- 14567483
TI  - Gastroesophageal reflux: medical and surgical treatment options.

PMID- 14567484
TI  - Are anticoagulants better than antiplatelet agents for treatment of acute
      ischemic stroke?

PMID- 14567485
TI  - Management of gastroesophageal reflux disease.
AB  - The primary treatment goals in patients with gastroesophageal reflux disease are
      relief of symptoms, prevention of symptom relapse, healing of erosive
      esophagitis, and prevention of complications of esophagitis. In patients with
      reflux esophagitis, treatment is directed at acid suppression through the use of
      lifestyle modifications (e.g., elevating the head of the bed, modifying the size
      and composition of meals) and pharmacologic agents (a histamine H2-receptor
      antagonist [H2RA] taken on demand or a proton pump inhibitor IPPI] taken 30 to 60
      minutes before the first meal of the day). The preferred empiric approach is step
      up therapy (treat initially with an H2RA for eight weeks; if symptoms do not
      improve, change to a PPI) or step-down therapy (treat initially with a PPI; then
      titrate to the lowest effective medication type and dosage). In patients with
      erosive esophagitis identified on endoscopy, a PPI is the initial treatment of
      choice. Diagnostic testing should be reserved for patients who exhibit warning
      signs (i.e., weight loss, dysphagia, gastrointestinal bleeding) and patients who
      are at risk for complications of esophagitis (i.e., esophageal stricture
      formation, Barrett's esophagus, adenocarcinoma). Antireflux surgery, including
      open and laparoscopic versions of Nissen fundoplication, is an alternative
      treatment in patients who have chronic reflux with recalcitrant symptoms. Newer
      endoscopic modalities, including the Stretta and endocinch procedures, are less
      invasive and have fewer complications than antireflux surgery, but response rates
      are lower.

PMID- 14567486
TI  - Information from your family doctor. Gastroesophageal reflux disease.

PMID- 14567487
TI  - A practical guide to anaphylaxis.
AB  - Anaphylaxis is a life-threatening reaction with respiratory, cardiovascular,
      cutaneous, or gastrointestinal manifestations resulting from exposure to an
      offending agent, usually a food, insect sting, medication, or physical factor. It
      causes approximately 1,500 deaths in the United States annually. Occasionally,
      anaphylaxis can be confused with septic or other forms of shock, asthma, airway
      foreign body, panic attack, or other entities. Urinary and serum histamine levels
      and plasma tryptase levels drawn after onset of symptoms may assist in diagnosis.
      Prompt treatment of anaphylaxis is critical, with subcutaneous or intramuscular
      epinephrine and intravenous fluids remaining the mainstay of management.
      Adjunctive measures include airway protection, antihistamines, steroids, and beta
      agonists. Patients taking beta blockers may require additional measures. Patients
      should be observed for delayed or protracted anaphylaxis and instructed on how to
      initiate urgent treatment for future episodes.

PMID- 14567488
TI  - Information from your family doctor. Anaphylaxis.

PMID- 14567489
TI  - Fever in the returned traveler.
AB  - With the rising popularity of international travel to exotic locations, family
      physicians are encountering more febrile patients who recently have visited
      tropical countries. In the majority of cases, the fever is caused by a common
      illness such as tracheobronchitis, pneumonia, or urinary tract infection.
      However, fever in returned travelers always should raise suspicion for a severe
      or potentially life-threatening tropical infection. In addition to the usual
      medical history, physicians should obtain a careful travel history, a description
      of accommodations, information about pretravel immunizations or chemoprophylaxis
      during travel, a sexual history, and a list of exposures and risk factors. The
      extent and type of lymphadenopathy are important diagnostic clues. Altered mental
      status with fever is an alarm symptom and requires urgent evaluation and
      treatment. Malaria must be considered in patients who traveled even briefly
      within an endemic area. Enteric fever is treated with fluoroquinolones, dengue
      fever with supportive measures only, leptospirosis with penicillin or
      doxycycline, and rickettsial infections with doxycycline.

PMID- 14567490
TI  - Diagnostic and therapeutic injection of the ankle and foot.
AB  - Joint and soft tissue injection of the ankle and foot region is a useful
      diagnostic and therapeutic tool for the family physician. This article reviews
      the injection procedure for the plantar fascia, ankle joint, tarsal tunnel,
      interdigital space, and first metatarsophalangeal joint. Indications for plantar
      fascia injection include degeneration secondary to repetitive use and traumatic
      injuries that are unresponsive to conservative treatment. Diagnostic aspiration
      or therapeutic injection of the ankle or first metatarsophalangeal joints can be
      performed for management of advanced osteoarthritis, rheumatoid arthritis, and
      other inflammatory arthritides such as gout, or synovitis or an arthrosis such as
      "turf toe." Persistent pain and disability resulting from tarsal tunnel syndrome,
      an analog of carpal tunnel syndrome of the wrist respond to local injection
      therapy. A painful interdigital space, such as that occurring in patients with
      Morton's neuroma, is commonly relieved with corticosteroid injection. The proper
      technique, choice and quantity of pharmaceuticals, and appropriate follow-up are
      essential for effective outcomes.

PMID- 14567491
TI  - Pharmacologic treatment of Alzheimer's disease: an update.
AB  - Alzheimer's disease is characterized by the development of senile plaques and
      neurofibrillary tangles, which are associated with neuronal destruction,
      particularly in cholinergic neurons. Drugs that inhibit the degradation of
      acetylcholine within synapses are the mainstay of therapy. Donepezil,
      rivastigmine, and galantamine are safe but have potentially troublesome
      cholinergic side effects, including nausea, anorexia, diarrhea, vomiting, and
      weight loss. These adverse reactions are often self-limited and can be minimized
      by slow drug titration. Acetylcholinesterase inhibitors appear to be effective,
      but the magnitude of benefit may be greater in clinical trials than in practice.
      The drugs clearly improve cognition, but evidence is less robust for benefits in
      delaying nursing home placement and improving functional ability and behaviors.
      Benefit for vitamin E or selegiline has been suggested, but supporting evidence
      is not strong. Most guidelines for monitoring drug therapy in patients with
      Alzheimer's disease recommend periodic measurements of cognition and functional
      ability. The guidelines generally advise discontinuing therapy with
      acetylcholinesterase inhibitors when dementia becomes severe.

PMID- 14567492
TI  - Sudden infant death syndrome.

PMID- 14567493
TI  - Air, air everywhere.

PMID- 14567494
TI  - ACIP releases 2003 guidelines on the prevention and control of influenza.

PMID- 14567495
TI  - The complete physical.

PMID- 14567496
TI  - Overweight, but not hypertension, is associated with SAH polymorphisms in
      Caucasians with essential hypertension.
AB  - The gene SAH (chromosome 16p12.3) is of interest in the etiology of human
      hypertension. In Caucasians a PstI restriction fragment length polymorphism
      (RFLP) of SAH has been correlated with body weight in individuals with
      hypertension. To extend this finding we carried out a case-control study of
      several recently identified polymorphisms in SAH: 1) an insertion/deletion of
      TTTAA at nucleotide --1037 in the promoter; 2) an insertion/deletion of two Alu
      like sequences in intron 1; and 3) an A-G variant in intron 12 located 7 bp
      upstream from exon 13. Subjects were 121 hypertensives with 2 hypertensive
      parents and 178 normotensives whose parents were both normotensive. All were
      Anglo-Celtic Caucasians and 51% of the hypertensives were overweight (body mass
      index (BMI)>25 kg/m2). The SAH promoter and intron 1 variants, but not the intron
      12 or PstI RFLP, were in linkage disequilibrium (LD) (D'=100%, p<0.001). We found
      no association between any of the polymorphisms and hypertension. However, the
      frequency of the minor allele of the intron 1 polymorphism (0.20) was higher in
      overweight than in normal weight hypertensives (0.07) (p=0.013). This association
      was supported by the weak tracking of plasma lipid variables with this allele (p
      values=0.01-0.04), although these lost their statistical significance after
      correction for multiple comparisons. In conclusion, the present data offers
      support for variation in SAH having a role in predisposition to overweight in
      hypertensives.

PMID- 14567497
TI  - Time-series analysis of systolic blood pressure variation in thirty-three Uygur
      centenarians in China.
AB  - The Uygur are reported to have an unusually long life expectancy. The purpose of
      this research was to perform a time-series analysis of systolic blood pressure
      (SBP) variations in the Uygur and clarify the role of blood pressure variation
      (BPV) in their longevity. A cross-sectional survey was carried out in Hotan. We
      investigated 133 clinically healthy elderly Uygur subjects and divided them into
      two groups: 1) 33 Uygur centenarians in Hotan (UCH; aged > or = 100 years); and
      2) 100 elderly Uygur in Hotan (UEH; aged 65-70 years). Blood pressure (BP) was
      monitored and analyzed with ambulatory BP monitoring. The frequency domain
      measures were obtained with the maximum entropy method. The mean 24-h SBP was
      higher in UCH than in UEH. The ratio of non-dipper type BPV was larger in the UCH
      than in UEH. The highest power spectral density occurred over a 12-h rather than
      a 24-h period in both UCH and UEH. Ultradian BPVs were more frequent in UCH than
      in UEH. The least square-fitting curves demonstrated that the maximum values,
      minimum values, and mean 24-h SBP values were higher in UCH than in UEH. The
      higher BP and greater number of ultradian BPVs in UCH may have been due to the
      greater energy expenditure for maintaining daily activities in this population.
      Factors such as meals, daytime naps, nocturnal micturition, decreased
      baroreceptor sensitivity, and arterial sclerosis may also have contributed to the
      higher ultradian BPVs. In conclusion, BPV in the 12-h is more dominant than in
      the 24-h in both UCH and UEH. BPVs in the 3-h and 4-h are more frequent in UCH
      than those in UEH.

PMID- 14567498
TI  - Microalbuminuria and cardiovascular events in elderly hypertensive patients
      without previous cardiovascular complications.
AB  - To assist in the development of better treatments for elderly hypertensive
      patients, we studied the degree to which the baseline values of urinary albumin
      excretion (UAE) and other cardiovascular risk factors were predictive of
      cardiovascular complications in a cohort of elderly hypertensive patients. In
      1994, we adopted 144 elderly hypertensive patients, who had been treated for more
      than 6 years at various clinics and more than 1 year at the National
      Cardiovascular Center, Osaka, Japan. They were divided into 2 groups: a NA group
      (n=111) with normoalbuminuria (UAE<30mg/day) and an MA group (n=33) with
      microalbuminuria (UAE 30-300 mg/day). At baseline, the two groups were similar
      with respect to systolic and diastolic blood pressure (SBP/DBP), pulse pressure
      (PP), age, ratio of males to females, serum creatinine, uric acid, total
      cholesterol, fasting plasma glucose (FPG), and creatinine clearance (CCr). PP was
      calculated as SBP minus DBP. The efficacy of blood pressure (BP) control was
      similar in both groups during the 8-year follow up period; however, a total of 14
      cardiovascular events occurred in the MA (6/33) and NA (8/111) groups, with the
      MA group showing the higher incidence rate by multiple logistic regression
      analysis (p<0.05). At 8 years of follow-up, PP and age were correlated with UAE
      (p<0.05, p<0.001). At the same time point, CCr was correlated with UAE at
      baseline (p<0.05). The results indicated that, in elderly hypertensive patients
      without previous cardiovascular complications, microalbuminuria can be a
      predictor of cardiovascular events irrespective of conventional BP control.

PMID- 14567499
TI  - Efficacy of various antihypertensive agents as evaluated by indices of vascular
      stiffness in elderly hypertensive patients.
AB  - When observed in elderly hypertensive patients, increased pulse pressure (PP) and
      arterial stiffness are known to be independent risk factors for cardiovascular
      diseases. Increased systolic blood pressure (SBP) leads to left ventricular
      hypertrophy, while decreased diastolic blood pressure (DBP) results in decreased
      coronary circulation. It is known that increased arterial stiffness is the major
      cause of increased PP. Thus basic morbid states of cardiac failure or ischemic
      heart diseases are more likely to develop in elderly hypertensive patients with
      increased PP and arterial stiffness, and there is need of antihypertensive drugs
      that decrease these effects in elderly hypertensives. In this study, we compared
      the effects of an angiotensin-receptor blocker (ARB: valsartan), an angiotensin
      converting enzyme inhibitor (ACE-I: temocapril), and long-acting Ca antagonists
      (L- and N-type Ca channel blocker: cilnidipine; and L-type Ca channel blocker:
      nifedipine CR) on PP and arterial stiffness measured by pulse wave velocity in
      elderly hypertensive patients for 3 months. The ARB yielded the largest
      reductions in PP and brachial-ankle pulse wave velocity (baPWV), followed by the
      ACE-I and L- and N-type Ca channel blocker, while the L-type Ca channel blocker
      yielded no improvement. The effects on arterial stiffness and PP thus varied
      among the drug characteristics. Although ARB achieved the largest reduction in
      baPWV, this decrease was not associated with any reductions in PP, SBP, DBP, or
      mean blood pressure, as were the baPWV-decreases achieved by the other drugs,
      suggesting that ARB may further reduce the risk of arteriosclerosis in elderly
      hypertensive patients by decreasing arterial stiffness in addition to its
      antihypertensive effect.

PMID- 14567500
TI  - Brachial-ankle pulse wave velocity as a marker of atherosclerotic vascular damage
      and cardiovascular risk.
AB  - The measurement of brachial-ankle pulse wave velocity (baPWV) is simple and
      applicable for general population studies. The present study was conducted to
      evaluate the applicability of baPWV for screening cardiovascular risk as well as
      for use as a marker of the severity of atherosclerotic vascular damage in a
      general population. baPWV was measured in a cross-sectional study involving two
      cohorts constituting a total of 10,828 subjects who underwent annual health
      screening check up examinations (6,716 males and 4,112 females; age 30 to 74
      years). The Framingham risk score and Pocock's score were obtained. Multivariate
      analysis demonstrated that baPWV was associated with both scores, independently
      from conventional atherosclerotic risk factors. The receiver-operator
      characteristic curve demonstrated that a baPWV of 14.0 m/s is useful for risk
      stratification by Framingham score and to discriminate patients with either
      stroke or coronary heart disease (n=143), but the likelihood ratios were less
      than 5.0. Logistic regression analysis demonstrated that a baPWV>14.0 m/s is an
      independent variable for the risk stratification by Framingham score and for the
      discrimination of patients with atherosclerotic cardiovascular disease. Thus,
      baPWV has potential as a new marker of cardiovascular risk and may be more useful
      than other conventional markers; in addition, baPWV is easy to obtain and serves
      as an indicator of either atherosclerotic cardiovascular risk or severity of
      atherosclerotic vascular damage; thus it is useful to screen the general
      population. While the discriminating powers are not sufficiently high, a cutoff
      value of 14.0 m/s serves to screen subjects, especially in middle-aged ones, of
      either gender.

PMID- 14567501
TI  - Effects of mitogen-activated protein kinase pathway and co-activator CREP-binding
      protein on peroxisome proliferator-activated receptor-gamma-mediated
      transcription suppression of angiotensin II type 1 receptor gene.
AB  - Peroxisome proliferator-activated receptor (PPAR)-gamma and its ligands suppress
      several genes related to atherogenesis. We previously reported that ligand
      activated PPAR-gamma suppressed angiotensin II type 1 receptor (AT1R) gene
      transcription in vascular smooth muscle cells (VSMCs) by the inhibition of Sp1
      binding to the --58/--34 GC-box related element in the AT1R gene promoter region
      via a protein-protein interaction. It has been reported that the mitogen
      activated protein (MAP) kinase pathway inhibits PPAR-gamma function through its
      phosphorylation, and co-activator CREB-binding protein (CBP)/p300 interacts with
      PPAR-gamma and modulates its activity. Since both the MAP kinase pathway and CBP
      have recently been reported to be atherogenic, we examined their effects on PPAR
      gamma-mediated AT1R gene transcription suppression. We observed that 1) PPAR
      gamma-mediated AT1R gene transcription suppression was augmented by treatment
      with the MAP kinase kinase inhibitor PD98059, while treatment with the p38 kinase
      inhibitor SB203580 showed no effect; 2) the PPAR-gamma-mediated AT1R mRNA
      decrease was also augmented by PD98059 treatment; 3) CBP overexpression
      partially, but significantly, abrogated PPAR-gamma-mediated AT1R gene
      transcription suppression; and 4) the CBP effect was eliminated when the --58/-
      34 GC-box related element was disrupted. It is therefore speculated that: 1) PPAR
      gamma phosphorylation by the MAP kinase pathway may attenuate PPAR-gamma-mediated
      AT1R gene transcription suppression through the inhibition of PPAR-gamma
      activity; and 2) CBP may enhance the activity of the remaining Sp1 on the --58/-
      34 GC-box related element, resulting in a reduction in PPAR-gamma-mediated AT1R
      gene transcription suppression. The MAP kinase pathway and CBP may thus
      antagonize against PPAR-gamma in AT1R gene transcription, probably leading to the
      progression of atherosclerosis.

PMID- 14567502
TI  - Acute regulation of the epithelial sodium channel gene by vasopressin and
      hyperosmolality.
AB  - The amiloride-sensitive epithelial sodium channel (ENaC) plays a key role in
      sodium reabsorption in the collecting ducts. We examined ENaC mRNA distribution
      along the nephron and acute effects of vasopressin and hyperosmolality on ENaC
      mRNA expression. ENaCalpha, beta, and gamma mRNA expressions were observed in
      cortical, outer medullary and initial inner medullary collecting ducts (CCD, OMCD
      and ilMCD, respectively). ENaCalpha mRNA expression was also observed in
      medullary and cortical thick ascending limbs (MAL and CAL, respectively), while
      ENaCbeta and gamma mRNA expressions were not observed. Furthermore, ENaCalpha
      mRNA expression in MAL but not in collecting ducts was stimulated by acute
      exposure to arginine vasopressin (AVP), 8-(4-chlorophenylthio) (CPT)-cAMP and
      hyperosmolality. However, the physiological significance of these effects is not
      known, since ENaC protein is reported to be absent in MAL. These data suggest
      that ENaCalpha mRNA expression in MAL but not in collecting ducts is acutely
      regulated by AVP and hyperosmolality. The absence of stimulation of ENaCalpha
      mRNA expression in collecting ducts suggests the physiological significance of
      ENaCbeta and gamma mRNA for acute regulation by vasopressin. Determining the
      physiological significance of the acute effect of vasopressin in MAL will require
      further investigations.

PMID- 14567503
TI  - Renoprotective effects of benidipine in combination with angiotensin II type 1
      receptor blocker in hypertensive Dahl rats.
AB  - We examined the effects of the angiotensin II type 1 receptor blocker
      candesartan, the calcium channel blockers benidipine and amlodipine, hydralazine,
      and the combination of candesartan and benidipine or amlodipine on blood pressure
      and renal function in Dahl salt-sensitive (DS) hypertensive rats. Male DS rats (5
      weeks of age) were fed a high-salt (8% NaCl) diet, resulting in hypertension
      accompanied by glomerular sclerosis and an increased urinary albumin excretion.
      Drugs were orally administered from 2 to 6 weeks after the start of the feeding.
      Although candesartan (1 or 10 mg/kg) had little effect on the blood pressure,
      benidipine (4 mg/kg), amlodipine (4 mg/kg) and hydralazine (5 mg/kg) had similar
      hypotensive effects. Benidipine, but not amlodipine, hydralazine, or candesartan,
      significantly inhibited the increase in the albuminuria and glomerular sclerosis.
      The combination of candesartan (1 mg/kg) and benidipine (4 mg/kg) lowered the
      levels of blood pressure and albuminuria more effectively than the combination of
      candesartan (1 mg/kg) and amlodipine (4 mg/kg). These results indicate that
      benidipine is effective in preventing the impairment of renal function in DS
      hypertensive rats, and suggest that additional benefits can be expected by
      combination therapy with benidipine and an angiotensin II type 1 receptor
      blocker.

PMID- 14567504
TI  - Impaired Ca2+ handling in perfused hypertrophic hearts from Dahl salt-sensitive
      rats.
AB  - To clarify the correlation between intracellular Ca2+ dynamics and level of Ca2+
      regulatory proteins, changes in Ca2+ handling and these proteins were
      investigated in a whole-heart experimental model of pressure-overload
      hypertrophy. We used 17-18-week-old male Dahl salt-sensitive rats (DS) and Dahl
      salt-resistant rats (DR) fed a high-salt diet. We monitored the fura-2
      fluorescence ratio, an index of cytoplasmic Ca2+ concentration ([Ca2+]i), using a
      Ca2+ analyzer in a retrograde perfused heart. Left ventricular pressure (LVP) and
      an electrocardiogram were simultaneously recorded. Ca2+ handling was assessed by
      exposing the hearts to 2 min of low-Na+ (70 mmol/l) perfusion to produce an
      increase in [Ca2+]i (n = 6), which was sensitive to Ni2+, a blocker of the
      Na+/Ca2+ exchanger (NCX). In another series, the hearts were stimulated at 2.5 to
      5 Hz to determine the Ca2+-force-frequency relationship (n = 6). DS rats showed
      marked cardiac hypertrophy without any signs of failure. The time-to-peak Ca2+
      transient was prolonged in DS compared with that in DR during normal beating.
      During low-Na+ exposure, the time-to-peak diastolic [Ca2+]i (TTP) and the decay
      time from peak [Ca2+]i (DT) were prolonged in DS compared with DR (TTP, 43.3 +/-
      4.0 vs. 32.5 +/- 2.5 s, p < 0.05; DT, 70.0 +/- 8.8 vs. 29.2 +/- 2.7 s, p <
      0.005). Following pretreatment with 10 mmol/l caffeine to inhibit sarcoplasmic
      reticulum (SR) function, TTP and DT were still prolonged in DS compared with DR
      (TTP, 64.2 +/- 9.7 vs. 37.0 +/- 5.8 s, p < 0.05; DT, 55.8 +/- 12.6 vs. 26.0 +/-
      5.7 s, p < 0.05). The force (LVP)-frequency relationship was initially positive
      in DR but was negative at all times in DS (%LVP/2.5 Hz: DS, 90.3 +/- 2.0%; DR,
      112.2 +/- 4.5%; p < 0.05). Elevation of diastolic [Ca2+]i (percent increase of
      baseline) was greater in DS than in DR with increased stimulation (5 Hz: DS, 80.7
      +/- 6.7%; DR, 52.1 +/- 5.9%; p < 0.05). In Western blot analysis, the protein
      level of NCX was equivalent, whereas that of SR Ca2+ ATPase (SERCA2) was
      significantly decreased in DS compared with DR. These results suggest that
      slowing of cellular Ca2+ mobilization and removal is related to impaired Ca2+
      handling in late-phase cardiac hypertrophy. Both the activity of the NCX and that
      of the SR may be affected. The SR dysfunction may be associated with change in
      protein level of SERCA2.

PMID- 14567505
TI  - Eicosapentaenoic acid suppresses basal and insulin-stimulated endothelin-1
      production in human endothelial cells.
AB  - cis-Polyunsaturated fatty acids such as eicosapentaenoic acid (EPA) are the major
      fatty acids contained in fish oil, and are known to affect the various
      physiological properties of cell membranes in humans. The present study
      investigated the effects of polyunsaturated fatty acids on endothelin-1 (ET-1)
      production in human umbilical vein endothelial cells (HUVECs) and on insulin
      activity. After addition of various concentrations of EPA, docosahexaenoic acid,
      arachidonic acid, or linoleic acid to a culture medium, the concentration of ET-1
      was measured using ELISA, and that of ET-1 mRNA was determined by RT-PCR. The
      results showed that EPA had the strongest inhibitory effect (p<0.05) on both
      basal ET-1 production and ET-1 mRNA levels. In addition, insulin (1 micromol/l)
      markedly increased ET-1 production, and EPA also significantly decreased the
      effect induced by insulin. Pretreatment with Ca2+ chelator EGTA (1 mmol/l), NOS
      inhibitor L-NAME (300 micromol/l), or calmodulin antagonist W-7 (300 micromol/l)
      inhibited NO production by EPA (100 micromol/l), but these pretreatments had no
      effect on ET-1 production by EPA. These findings suggest that EPA reduces basal
      and insulin-enhanced ET-1 production by inhibiting ET-1 mRNA production. These
      effects of EPA may contribute to its vasorelaxant and anti-atherosclerotic
      effects.

PMID- 14567506
TI  - A case of aldosterone-producing adrenocortical adenoma associated with a probable
      post-operative adrenal crisis: histopathological analyses of the adrenal gland.
AB  - We describe a case of aldosterone-producing adrenocortical adenoma (APA)
      associated with a probable post-operative adrenal crisis possibly due to subtle
      autonomous cortisol secretion. The patient was a 46-year-old female who suffered
      from severe hypertension and hypokalemia. CT and MRI scans revealed a 2-cm
      diameter adrenal mass. The patient's plasma aldosterone level was increased, and
      her plasma renin activity was suppressed, both of which findings were consistent
      with APA. Cushingoid appearance was not observed. Morning and midnight serum
      cortisol and plasma adrenocorticotropic hormone (ACTH) levels were all within the
      normal range. Her serum cortisol level was suppressed to 1.9 microg/dl as
      measured by an overnight 1-mg dexamethasone suppression test, but was
      incompletely suppressed (2.7 microg/dl) by an overnight 8-mg dexamethasone
      suppression test. In addition, adrenocortical scintigraphy showed a strong uptake
      at the tumor region and a complete suppression of the contra-lateral adrenal
      uptake. After unilateral adrenalectomy, she had an episode of adrenal crisis, and
      a transient glucocorticoid replacement improved the symptoms. Histopathological
      studies demonstrated that the tumor was basically compatible with APA. The clear
      cells in the tumor were admixed with small numbers of compact cells that
      expressed 17alpha-hydroxylase, suggesting that the tumor was able to produce and
      secrete cortisol. In addition, the adjacent non-neoplastic adrenal cortex showed
      cortical atrophy, and dehydroepiandrosterone sulfotransferase immunoreactivity in
      the zonae fasciculata and reticularis was markedly diminished, suggesting that
      the hypothalamo-pituitary-adrenal (HPA) axis of the patient was suppressed due to
      neoplastic production and secretion of cortisol. Together, these findings
      suggested that autonomous secretion of cortisol from the tumor suppressed the HPA
      axis of the patient, thereby triggering the probable post-operative adrenal
      crisis. Post-operative adrenocortical insufficiency should be considered in
      clinical management of patients with relatively large APA, even when physical
      signs of autonomous cortisol overproduction are not apparent.

PMID- 14567507
TI  - Effect of testosterone and oestradiol-17beta on canine hair follicle culture.
AB  - Skin biopsies were taken from four body sites (head, thorax, flank and perineum)
      of three male entire Beagles and the primary hair follicles were isolated.
      Culture conditions were established to keep the hair follicles growing for up to
      7 days. Additionally, hair follicles were incubated in supplemented medium
      (containing insulin, transferrin, glutamine and sodium selenite) with or without
      the addition of testosterone (T) (1, 10 or 100 ng/ml) or oestradiol-17beta
      (E2beta) (0.01, 0.1 or 1 ng/ml), respectively and the daily growth of hair
      follicles was measured. In vitro daily growth of hair follicles from the thorax
      was stimulated by the low concentration of both hormones, but the growth of those
      from the flank was inhibited by the high concentration of both hormones. Hair
      follicles from the head were positively influenced by the lowest concentration of
      T and the medium concentration of E2beta. The daily growth of hair follicles from
      the perineum was not significantly influenced by either hormone.

PMID- 14567508
TI  - Near-infrared spectroscopy evaluated as a technique for estimating udder
      haemodynamics in the lactating cow.
AB  - Near-infrared spectroscopy (NIRS) that requires few compact instruments is a non
      invasive and continuous method of monitoring haemodynamics in living organs. To
      assess the feasibility of using NIRS in evaluating the udder haemodynamics in six
      dairy cows, a probe component consisting of a light-emitting diode and a
      phototransistor was attached to the left side of the udder surface. Real-time
      variation of tissue haemodynamics was analysed and the data were transferred to
      the computer by way of a radiotelemetry system. On induction of temporary
      congestion by applying pressure with the hand pressed firmly against the left
      milk vein for 20 s, concentration of oxyhaemoglobin decreased throughout the 20-s
      duration of congestion, and concentration of deoxyhaemoglobin increased. A surge
      in blood volume was also observed from the beginning of congestion, then the
      volume attenuated to baseline. The data demonstrated that the reading seen on the
      monitor reflects the real-time status of the mammary gland. NIRS shows promise as
      a useful approach to physiological studies.

PMID- 14567509
TI  - Influence of shearing on the circadian rhythm of body temperature in the sheep.
AB  - The presence of functional rhythmic variations is a well-demonstrated phenomenon
      at all levels of physiological organization and especially in the functioning of
      the cell components, of tissues and of organic systems. In domestic animals, the
      body temperature presents spontaneous and regular periodic oscillations over
      different periods of time, which are the result of complex mechanisms that
      witness the existence of endogenous and exogenous factors. Taking this knowledge
      as a starting-point, the authors studied 12 Comisana breed ewes to observe the
      influence of shearing on the circadian periodicity of rectal and skin
      temperature. The obtained results show the transient loss of body temperature
      rhythm by shearing, with an exogenous component, the shearing itself, and an
      endogenous component, the modifications of metabolic levels induced by the
      removal of the fleece, the external insulating layer.

PMID- 14567510
TI  - Long-term follow-up of manipulative treatment in a horse with back problems.
AB  - In order to objectively quantify the effect of manipulation on back-related
      locomotion anomalies in the horse, a recently developed kinematic measuring
      technique for the objective quantification of thoracolumbar motion in the horse
      was applied in a dressage horse that was suffering from a back problem. In this
      horse, clinically, a right-convex bending (scoliosis) from the 10th thoracic
      vertebra to the second lumbar vertebra was diagnosed. As a result, there was a
      marked asymmetric movement of the thoracolumbar spine. Functionally, there was
      severe loss of performance. Thoracolumbar motion was measured in terms of
      ventrodorsal flexion, lateral flexion, and axial rotation using an automated gait
      analysis system. Measurements were repeated before and 2 days after treatment,
      before the second treatment 3 weeks later, and at 4 weeks and 8 months after the
      second treatment to assess long-term effect. At the same time, performance of the
      horse was assessed subjectively by the trainer as well. Symmetry of movement
      improved dramatically after the first treatment. After this, there was a slight
      decrease in symmetry, but 8 months after the last treatment the symmetry indexes
      for the various joints were still considerably better than during the first (pre
      treatment) measuring session. Subjectively, the trainer did not notice
      improvement until after measurement session 4. Between sessions 4 and 5 (at 4
      weeks and 8 months after the second treatment) there was a change of trainer. The
      new trainer did not report any back problem, and succeeded in bringing the horse
      back to its former level in competition. It is concluded that manipulation had a
      measurable influence on the kinematics of the thoracolumbar spine. However, it is
      recognized that an improvement in symmetry of motion is not equivalent to
      clinical improvement and that other measures, such as changes in management, may
      be more decisive.

PMID- 14567511
TI  - The effect of orally administered marbofloxacin on the pharmacokinetics of
      theophylline.
AB  - As certain quinolones can interfere with the metabolism of theophylline by
      competitive inhibition of the hepatic microsomal cytochrome P450 system,
      concomitant use of these drugs with theophylline could result in theophylline
      toxicity. This study investigated the effect of orally administered marbofloxacin
      (2 and 5 mg/kg each once daily) on steady-state plasma pharmacokinetics of
      theophylline after concomitant oral administration of a sustained release
      theophylline preparation in dogs. Marbofloxacin caused some alteration in
      theophylline metabolism. A 2 mg/kg dose of marbofloxacin did not clearly result
      in an increased area under the concentration--time curve (AUC) or decreased
      clearance of theophylline, but at a dose of 5 mg/kg, a statistically significant
      increase in AUC and a decrease in the total clearance of theophylline was found.
      The 26% reduction in theophylline clearance is probably not clinically
      significant in healthy dogs, but for dogs with renal impairment, there might be a
      chance of theophylline accumulation when dosed concomitantly with marbofloxacin.

PMID- 14567512
TI  - The variations of white blood cell count in Lipizzan horses.
AB  - Total and differential leucocyte counts (lymphocytes, neutrophils, monocytes,
      eosinophils and basophils) were measured in 140 stallions, 101 mares and 25 foals
      of Lipizzan breed. The values fell in the normal ranges for warm-blooded horses.
      Differences between mares and stallions were not significant with the exception
      of foals, having higher white blood cell, neutrophil, lymphocyte, monocyte and
      basophil values in females than in males. Foals exhibited an age-related increase
      of total leucocyte count during the first 4 months of life, accompanied by a
      decrease in neutrophil and increase in lymphocyte and eosinophil counts. In mares
      and stallions, the total number of leucocytes, lymphocytes, monocytes and
      basophils significantly decreased but the number of neutrophils and eosinophils
      remained almost unchanged with age gain.

PMID- 14567513
TI  - Interaction between epidurally administered ketamine and pethidine in dogs.
AB  - The present study was designed to test the hypothesis that a synergistic
      interaction could be recorded after epidural administration of ketamine-an N
      methyl-D-aspartate (NMDA) antagonist and pethidine--an opioid agonist. Twelve
      adult mongrel dogs of either sex were randomly divided in three groups A, B and C
      of four animals each. Ketamine (5%) at 2.5 mg/kg and pethidine (3%) 2 mg/kg were
      injected at lumbosacral epidural space in animals of groups A and B,
      respectively. In animals of group C ketamine (2.5 mg/kg) and pethidine (2 mg/kg)
      were injected. Heart rate increased significantly up to 15 min in group A,
      whereas in groups B and C, the increase was non-significant for a period of 10
      and 45 min, respectively. Respiration increased gradually up to 45-60 min in
      group A and for 15-20 min in group B. However, in animals of group C respiration
      fell below the baseline during the first 10-15 min and then returned near the
      baseline. Rectal temperature decreased only marginally in all the groups.
      Ketamine alone produced complete analgesia at tail and perineal region for a
      period of 5-10 min and then moderate analgesia for the next 20-30 min. Analgesia
      at the flank was moderate to complete between 5 and 15 min. In group B complete
      analgesia was only moderate at the tail and perineal region up to 30 min. In
      animals of group C, complete analgesia was observed only at perineal region for a
      very short period (5 min). Analgesia was not associated with sedation in any of
      the groups but animals of groups A and C showed signs of motor incoordination.
      Results of the study suggest rather antagonistic than synergistic interaction
      between epidurally administered ketamine and pethidine. Further studies are
      needed to confirm the antagonistic interaction between the two drugs.

PMID- 14567514
TI  - Effect of oral enrofloxacin and florfenicol on pigs experimentally infected with
      Actinobacillus pleuropneumoniae serotype 1.
AB  - This study was carried out to compare the efficacy of two oral anti-microbials as
      metaphylactic medication to pigs inoculated with Actinobacillus pleuropneumoniae
      serotype 1. Forty-two pigs with an average weight of 22.64 kg were randomly
      assigned to three treatment groups: group F was given doses of 40 ppm of
      florfenicol, group E received 150 ppm of enrofloxacin and group C received no
      medication. Groups F and E received medicated feed 12 h before being inoculated
      and for 7 days after inoculation. All the pigs were inoculated by aerosol, with 2
      x 10(7) CFU/ml of A. pleuropneumoniae serotype 1 each. The average body
      temperature was higher in group C than in groups E and F, between 12 and 96 h
      after inoculation (P < 0.05). No differences were found between groups F and E in
      respiration pattern, nasal secretion and general condition (P > 0.05): however,
      differences were found in group C for respiration pattern and general condition
      (P < 0.05), 12 h after inoculation. There was no mortality in groups F and E,
      whereas a 50% mortality was recorded in group C during the first 48 h after
      inoculation (P < 0.05). Necropsies and bacterial cultures were performed 12 days
      after inoculation. Lesions were observed in five pigs of group F (35.71%) with an
      average damage of 1.16%; in four pigs of group E (28.57%) with 1.24%; and in 13
      animals in group C (92.85%) with 34.5% of affected lung tissue (P < 0.05). The
      infective agent was cultured from various organs of animals in groups F and C,
      but not from those in group E.

PMID- 14567515
TI  - Effects of Nigella sativa L. and Urtica dioica L. on lipid peroxidation,
      antioxidant enzyme systems and some liver enzymes in CCl4-treated rats.
AB  - This study was designed to investigate the effects Nigella sativa L. (NS) and
      Urtica dioica L. (UD) on lipid peroxidation, antioxidant enzyme systems and some
      liver enzymes in carbon tetrachloride (CCl4)-treated rats. A total of 60 healthy
      male Sprague-Dawley rats were utilized in this study. The rats were randomly
      allotted into one of four experimental groups: A (CCl4-only treated), B (CCl4 +
      UD treated), C (CCl4 + NS treated) and D (CCl4 + UD + NS treated), each
      containing 15 animals. All groups received CCl4 [0.8 ml/kg of body weight,
      subcutaneously, twice a week for 90 days starting day 1]. In addition, B, C and D
      groups also received daily intraperitoneal injections of 0.2 ml/kg NS or/and 2
      ml/kg UD oils for 45 days starting day 46. Group A, on the other hand, received
      only 2 ml/kg normal saline solution for 45 days starting day 46. Blood samples
      for the biochemical analysis were taken by cardiac puncture from five randomly
      chosen rats in each treatment group at beginning, at 45th and at 90th day of the
      experiment. The CCl4 treatment for 45 days increased the lipid peroxidation and
      liver enzymes, and also decreased the antioxidant enzyme levels. NS or UD
      treatments (alone or combination) for 45 days starting day 46 decreased the
      elevated lipid peroxidation and liver enzyme levels and also increased the
      reduced antioxidant enzyme levels. Live weights of the rats decreased in group A,
      and increased in groups B, C and D. It is concluded that NS and UD decrease the
      lipid peroxidation and liver enzymes, and increase the antioxidant defence system
      activity in the CCl4-treated rats.

PMID- 14567516
TI  - Cerebral high-grade astrocytoma (glioblastoma) in a cat.
AB  - A cerebral tumour was found in the right frontal lobe of a 7-year-old female
      mongrel cat. The mass showed infiltrative growth and caused deformation of the
      corpus callosum. Histopathologically, the tumour cells showed anaplasia,
      pleomorphism and mitotic figures. Necrosis and vascular proliferation were
      prominent. The neoplastic cells surrounded areas of necrosis, but as an
      indistinct pseudopalisade formation. Immunohistochemically, low numbers of tumour
      cells labelled positively for anti-glial fibrillary acidic protein and anti-S100
      protein. Electron microscopically, the majority of tumour cells had no filaments
      and cytoplasmic processes, but the differentiated cells presented cytoplasmic
      filaments and glycogen granules. Based on these findings, the tumour was
      diagnosed as cerebral high-grade astrocytoma, glioblastoma.

PMID- 14567517
TI  - Increased central venous pressure in a patient with pruritic skin lesions.

PMID- 14567518
TI  - Immunomodulation by antimicrobial drugs.
AB  - Immunomodulation aims at either enforcement of host defence mechanisms or
      dampening of the inflammatory response of the host. Thus, immunomodulatory drugs
      may enhance host defence by either stimulating the inflammatory response or
      inhibiting the counter-regulatory, anti-inflammatory response. On the other hand,
      the response of the host may be down-modulated through inhibition of the
      inflammatory response or induction of counter-regulatory, anti-inflammatory
      mechanisms. Antimicrobial drugs may have such immunomodulatory effects, but so
      far these effects have not been exploited clinically.

PMID- 14567519
TI  - Severe acute respiratory syndrome: lessons and uncertainties.
AB  - The outbreak of severe acute respiratory syndrome (SARS) has produced scientific
      and epidemiological discoveries with unprecedented speed, and this information
      has been spread instantaneously to the global health community through the
      internet. Within a few weeks, the coronavirus associated with SARS (SARS-CoV) was
      identified and sequenced. The source of the outbreak and the exact modes of
      transmission are still subjects of research. Important lessons can be learned
      from the SARS outbreak about both the scientific and the public health approach
      to emerging pathogens.

PMID- 14567520
TI  - Ribavirin in the treatment of severe acute respiratory syndrome (SARS).

PMID- 14567521
TI  - Macrolide antibiotics, bacterial populations and inflammatory airway disease.
AB  - Chronic obstructive pulmonary disease (COPD) and other inflammatory airway
      conditions are major causes of morbidity and mortality worldwide. Antibiotics are
      used to treat acute infectious exacerbations of airway disease. However, for the
      macrolides, a significant and growing body of evidence indicates that anti
      inflammatory effects of these antibiotics, which may be independent of their
      antibacterial effects, are at least partially responsible for their beneficial
      effect. In this review, we describe current thinking on the means whereby anti
      inflammatory effects of macrolides impact chronic airway disease. The current
      data indicate that some macrolides have immunomodulatory activity, mediated at
      least in part by effects on the activation of gene transcription mediated by NF
      kappabeta activation that may be separable from their antimicrobial activities,
      and could explain their surprising efficacy in asthma and viral infections for
      which the role of bacteria is not established. Other, provocative work indicates
      that subclinical doses of macrolides may also affect signalling within and
      between bacterial communities, and thus impact developmental processes such as
      biofilm formation that are important in the establishment and persistence of
      chronic infections. The current data clearly suggest that activities beyond
      antimicrobial effects contribute significantly to the beneficial effect of
      macrolide therapy on inflammatory conditions.

PMID- 14567522
TI  - Compassionate use programme of irinotecan in colorectal cancer patients in The
      Netherlands.
AB  - BACKGROUND: Irinotecan is an effective treatment for metastatic colorectal
      cancer. However, its use may be associated with troublesome adverse effects such
      as delayed diarrhoea, acute cholinergic syndrome and neutropenic infection. The
      manufacturer decided to release irinotecan for compassionate use in The
      Netherlands prior to its regulatory approval (June 1998) and first introduction
      for second-line treatment of metastatic colorectal cancer. In view of the drug's
      adverse effect profile this was done in a carefully controlled manner. METHODS:
      Irinotecan was made available to patients with colorectal cancer with elaborate
      precautions. Treating physicians requesting irinotecan for compassionate use
      received a protocol, providing recommendations for the proper use and the
      prevention/management of potentially troublesome adverse events. Limited
      demographic, toxicity and efficacy data were collected. RESULTS: Between June
      1997 and September 1998, 112 patients were registered for this programme, 103 of
      whom actually received irinotecan. The percentage of patients experiencing grade
      3-4 adverse effects was relatively low: delayed diarrhoea in 17%, nausea and
      vomiting 17%, acute cholinergic syndrome 6%, febrile neutropenia 4% and
      neutropenic infection 2%. Five partial tumour responses and a high proportion of
      patients with 'no change' were noted. CONCLUSIONS: The carefully controlled
      release of irinotecan for compassionate use with a very detailed protocol for
      guidance and advice on safety precautions seems to have contributed to the
      relatively safe use of the drug outside the setting of a formal clinical trial.

PMID- 14567523
TI  - Nightmares, sleep and cardiac symptoms in the elderly.
AB  - BACKGROUND: Sleep complaints and various sleep symptoms are common in elderly
      persons with cardiac diseases. Nightmares are associated with profound sleep
      disturbances. METHODS: The present questionnaire survey with questions on sleep
      symptoms, nightmares and cardiac symptoms comprised 6103 elderly subjects (39.5%
      men). RESULTS: Nightmares occurred rather often in 6.9% and very often in 2.1% of
      the men. The corresponding frequencies in women were 9.6 and 2.3%, respectively.
      Irregular heart beats were reported by 11.8% of the men and 131% of the women
      (NS). Spasmodic chest pain occurred in 12.9 and 10.6%, respectively (p < 0.01).
      Irregular heart beats increased in association with increasing nightmares in both
      men (p < 0.01) and women (p < 0.0001). The percentages of men and women with both
      irregular heart beats and spasmodic chest pain were three times and seven times
      higher, respectively, among those who had nightmares very often than among those
      who very seldom or never had nightmares. The increase in cardiac symptoms in
      nightmare sufferers was not attributable to an increase in medication with
      cardiac drugs. CONCLUSION: In this group of elderly men and women increased
      nightmares were associated with an increase in irregular heart beats and
      spasmodic chest pain.

PMID- 14567524
TI  - Rituximab in the treatment of relapsing idiopathic thrombocytopenic purpura.
AB  - About 25 to 30% of patients with idiopathic thrombocytopenic purpura (ITP) are
      resistant to standard treatment with steroids and splenectomy. In these patients
      with chronic refractory ITP, there is no proven algorithm for standard care.
      Recently, the chimeric anti-CD20 monoclonal antibody rituximab was considered as
      an alternative treatment option in this patient group. We present a patient with
      frequently relapsing ITP after treatment with prednisone, splenectomy and high
      dose dexamethasone. Since he experienced increasing side effects due to the
      steroids, he was treated with rituximab 375 mg/m2, once weekly for four weeks,
      resulting in a complete long-lasting response (follow-up seven months).

PMID- 14567525
TI  - Acute pancreatitis after a course of clarithromycin.
AB  - We present a case of acute pancreatitis after a course of clarithromycin. An 84
      year-old woman died of suspected pneumonia and cardiac failure. Autopsy
      surprisingly revealed acute pancreatitis. Except for the use of clarithromycin no
      other cause for her acute pancreatitis was obvious. Pancreatitis induced by
      clarithromycin has been reported twice in the English literature so far. There
      are, however, a few reports on acute pancreatitis associated with other macrolide
      antibiotics, such as erythromycin and roxithromycin.

PMID- 14567526
TI  - Why is the measurement of jugular venous pressure discredited?
AB  - Every doctor should be able to make a probable diagnosis of congestive heart
      failure by clinical examination. The most revealing clinical sign is an elevated
      jugular venous pressure. The measurement of this pressure was introduced by Lewis
      in 1930 and refined and standardised by Borst and Molhuysen in 1952. Still, this
      method has fallen into disuse and is thought to be not very sensitive for
      diagnosing congestive heart failure. A study of the methods described in the
      literature reveals that variations in technique are responsible for great
      differences in normal values. It is argued that smaller elevations of jugular
      venous pressure can only be measured reliably by adhering strictly to the
      conditions put forward by Borst and Molhuysen. In this way the sensitivity will
      improve considerably. A plea is made for an intensive training in this method for
      doctors and medical students.

PMID- 14567527
TI  - What haemophilia could learn from the sickle cell work in the International
      Cochrane Collaboration.
AB  - It is well recognized that individuals required to make informed decisions about
      healthcare interventions often do not have ready access to reliable reviews of
      the available evidence, with healthcare professionals, researchers, policy makers
      and consumers often overwhelmed by unmanageable amounts of information. Expert
      reviews go some way to presenting new information in a concise and readable
      format. However, these are generally not subject to the same scientific rigour as
      the actual primary research they summarize. The International Cochrane
      Collaboration was established to address this need through the development and
      publication of rigorous, peer-reviewed, well-performed systematic reviews. This
      article will briefly summarize the basic principles of the Cochrane
      Collaboration, primarily focusing on its work in the field of inherited
      haemoglobinopathies, in particular sickle cell disease, and highlight potential
      areas of interest for haemophilia.

PMID- 14567528
TI  - Haemophilia--paucity of evidence, ways forward?
AB  - Although the basic management of people with haemophilia is agreed, much of this
      is based on historical experience. By today's standards the precise details of
      how much treatment is enough are not based on a good evidence framework. Although
      regular treatment with prophylaxis is widely believed to be optimal, the evidence
      for this has not been considered strong enough by some authorities to justify the
      considerably increased expenditure. Reviews available on the Cochrane Database
      provide regularly updated evidence in a given field and, where there is
      inadequate evidence, a review may identify what kinds of trials are needed. The
      Cochrane Review Group have identified 152 references to 127 trials relating to
      haemophilia A and B, and von Willebrand disease. Most of the trials in
      haemophilia are short-term comparisons of treatments such as trials with
      coagulation factor concentrates, or studies of antiviral agents. One study of
      bleeding prophylaxis ('Clotting factor concentrates given to prevent bleeding and
      bleeding-related complications in people with haemophilia A and B') has been
      designed but is not yet completed, and another title ('Management of inhibitors
      with haemophilia A') has been registered. Some preliminary questions can
      establish areas where new clinical studies are needed.

PMID- 14567529
TI  - Specialised services commissioning and primary care trusts.
AB  - Specialised services commissioners play an important role in the maintenance of
      excellent treatment standards within the UK. This review describes the
      involvement of the primary care trusts (PCTs) in specialised commissioning, as
      well as existing arrangements for the provision of specialised services in
      haemophilia. The article also examines the aims, objectives and preliminary
      findings of the ministerial review of commissioning arrangements for specialised
      services in England and some other parts of the UK, which is currently underway.

PMID- 14567530
TI  - The incidence of inhibitor development according to specific mutations--and
      treatment?
AB  - The spectrum of mutations in the factor VIII (FVIII) gene was investigated in a
      cohort of patients with severe haemophilia A, together with the relationship
      between mutation type and inhibitor development DNA analysis was undertaken on 55
      previously untreated patients in the Recombinate PUP mutation study who had all
      received the same clotting factor treatment and underwent regular monitoring for
      inhibitor development. Overall, 35% of patients with 'severe molecular defects'-
      intron 22 inversions, large deletions or stop mutations--developed an inhibitor.
      None of the patients with small insertions or deletions developed inhibitors. The
      patient numbers in this study were too small for analysis of mutation location
      effect and therefore an analysis of a large electronic patient database,
      HAMSTeRS, was undertaken. This revealed that 40% of patients with large deletions
      and 35% of patients with nonsense mutations developed inhibitors. This large
      database of information allowed further stratification by examination of the
      location of mutations within the FVIII gene and the type of sequence affected by
      the mutation. Nonsense and missense mutations in the light chain were associated
      with a higher risk of inhibitor formation than those occurring in the heavy
      chain. Small deletions or insertions affecting an A residue in a run of A
      residues were associated with a lower risk of inhibitor formation than deletions
      or insertions affecting other sequences. Splicing errors demonstrated the lowest
      inhibitor risk of any mutation type. These results may enable patients at higher
      risk of inhibitor formation to be identified. This may have consequences for the
      design of clinical trials and treatment options available to high-risk patients.

PMID- 14567531
TI  - Management of acquired haemophilia A--more questions than answers.
AB  - This paper discusses selected reports on the management of acquired haemophilia
      A, a rare bleeding disorder characterized by the development of an autoantibody
      directed against plasma coagulation factor VIII (FVIII) (Morrison et al., Blood
      81:1513-1520, 1993). The current literature consists of reports of cohorts of
      patients from referral centres and retrospective surveys of referral centres
      (Green and Lechner, Thromb Haemost 45:200-203, 1981). This suggests that the
      current literature may be biased both by referral practice to tertiary centres
      and reporting bias of these centres and may not be representative of the full
      spectrum of the disease. The published studies describe various immunosuppressive
      regimens to eradicate factor VIII inhibitors but usually lack control patients.
      Only one report describes a randomized, controlled study. Studies that address
      treatment of bleeding episodes give data on safety and efficacy for individual
      products but no comparative studies are available.

PMID- 14567532
TI  - Dose optimization of recombinant factor VIIa in the treatment of acute bleeding
      in haemophilia-associated inhibitors.
AB  - Recombinant coagulation factor VIIa (rFVIIa; NovoSeven) represents an important
      advance in the therapy for haemophilia patients with inhibitors. Since licensure,
      the standard dosing has been perceived as 90-120 microg/kg every 2-3 h until
      cessation of bleeding. There has been an accumulation of anecdotal experience
      with the use of higher, less frequent dosing of rFVIIIa, and a controlled
      clinical trial is underway to assess the safety and efficacy of the current
      dosing recommendation and a single dose of 270 microg/kg. Furthermore, a post
      licensure database is being analysed to evaluate the current dosing in acute
      bleeding episodes. Treatment, efficacy, and safety data from haemophilia patients
      with inhibitors treated with rFVIIa in a variety of contexts, including the on
      demand treatment of acute bleeding, were entered into the registry. Data from
      patients treated with bolus infusion of rFVIIa were analysed and bleeding
      episodes were grouped according to total rFVIIa dose administered. Registry data
      suggest that rFVIIa is both safe and effective at doses > 200 microg/kg and that
      efficacy improves with increased dose. The database is currently being analysed
      to determine if increasing dose is associated with an elimination of the need for
      repeat dosing.

PMID- 14567533
TI  - Catalytic antibodies to factor VIII in haemophilia A.
AB  - The development of factor VIII (FVIII) inhibitors in haemophiliac patients
      following therapeutic administration of exogenous FVIII is one of the major
      factors complicating the treatment of this disease. Most FVIII inhibitors
      described to date appear to be directed towards epitopes involved in the
      procoagulant activity of FVIII. However, recent data suggest that some FVIII
      inhibitors may behave as catalytic antibodies, able to cleave FVIII by
      hydrolysis. This appears to be the first example of catalytic antibodies having a
      direct role in the etiology of a disease. Further characterization of these
      catalytic anti-FVIII antibodies may lead to the identification of novel
      therapeutic approaches for the future management of FVIII inhibitor patients.

PMID- 14567534
TI  - Analysis and results of the recombinant factor VIIa extended-use registry.
AB  - This paper describes the analysis of recombinant factor VIIa (rFVIIa; NovoSeven;
      Novo Nordisk, Bagsvaerd, Denmark) use in 40 patients with intractable bleeding in
      the UK. All cases were reported on the 'rFVIIa extended use database' (Traumanet)
      between its launch in February 1999 and 12 March 2002. Twenty-one other cases
      reporting rFVIIa use in different circumstances were excluded from the analysis.
      Recombinant FVIIa was effective in stopping or markedly reducing blood loss in
      80% of patients; 20% of patients did not respond to treatment. Non-responders
      tended to have more deranged coagulation and lower platelet counts compared with
      responders. Despite a wide range of underlying illnesses, including malignancy
      and sepsis, few patients suffered adverse events. Thrombotic events occurred in
      three of 40 (7.5%) patients and these patients were considered as already at risk
      of thrombosis from other causes. The data suggest that rFVIIa is safe and
      effective therapy in patients with uncontrollable haemorrhage.

PMID- 14567535
TI  - Update on Novo Nordisk's clinical trial programme on NovoSeven.
AB  - Recombinant coagulation factor VIIa (rFVIIa; Novoseven, Novo Nordisk A/S,
      Bagsvaerd, Denmark) is registered in most regions of the world for the treatment
      of bleeding episodes in haemophilia patients with inhibitors to factor VIII or
      IX. Since its initial availability, there have been several case stories on the
      investigational use of rFVIIa as a haemostatic agent in a variety of bleeding
      patients. Novo Nordisk recognizes the need to establish clinical guidance, and
      when possible, regulatory approvals for indications with bleeding episodes of
      various aetiologies. Currently, the safety and efficacy of rFVIIa is being
      investigated in 11 multinational, phase II trials, involving more than 1500
      patients. Most of these trials have been designed to establish the efficacy of
      rFVIIa as a rescue treatment in episodes of severe life-threatening (upper
      gastrointestinal bleeding, stem cell transplantation, intra-cerebral haemorrhage
      and trauma). The remaining focus is on the prophylactic use of rFVIIa to improve
      haemostasis during surgery (orthotopic liver transplantation and liver
      resection), with the aim of avoiding or reducing the need for blood transfusions.
      In addition, Novo Nordisk is also continuing studies in haemophilia patients with
      inhibitors to increase therapeutic knowledge within this indication. Studies
      addressing dosages and regimens in subpopulations are presently ongoing.

PMID- 14567536
TI  - New insights into haemostasis in liver failure.
AB  - The precise mechanisms leading to the coagulopathy of acute liver injury are
      unclear. To study this further, coagulation and immune changes have been compared
      in patients with acute liver injury secondary to paracetamol overdose, with
      chronic cirrhosis, and normal healthy controls. In acute liver injury,
      coagulation factors II, V, VII and X were reduced to a similar degree, and were
      significantly lower than factors IX and XI. In cirrhosis, by contrast, these
      coagulation factors were reduced to similar levels. Factor VIII increased in
      acute liver injury, but was normal in cirrhosis. Interleukin-6 and tumour
      necrosis factor-alpha levels increased in both patient groups, but were higher in
      paracetamol overdose. Thrombin-antithrombin and soluble tissue factor levels
      increased in those with acute liver injury, but were normal in patients with
      cirrhosis. Functional antithrombin was reduced in both acute liver injury and
      cirrhosis. It is hypothesized that in acute paracetamol-induced liver injury,
      immune activation leads to tissue factor-initiated consumption of factors II, V,
      VII and X, but that levels of factors IX and XI are better preserved because of
      inhibition of the thrombin-induced amplification phase of coagulation. These
      findings have implications for appropriate coagulation factor support for
      patients with acute liver injury.

PMID- 14567537
TI  - Factor VII deficiency.
AB  - As yet, there have been neither systematic reviews nor reports of randomized,
      controlled trials involving factor VII (FVII) deficiency. Hence, a picture of
      this disorder can only be drawn by reviewing and summarizing the data that is
      available. This article provides an overview of the understanding of this rare,
      inherited disorder of coagulation. In particular, the status of current knowledge
      of the disorder's prevalence, clinical presentation, diagnostic characteristics
      and molecular genetics is reviewed, followed by a summary of currently available
      options for its treatment and management.

PMID- 14567538
TI  - Four factor deficiency.
AB  - Four factor deficiency is variably associated with mild to fatal bleeding. We
      describe a 3-month-old boy, born of consanguineous parents, who presented with a
      right subdural haematoma and a clotting screen showing a prothrombin time (PT) >
      100 s, an activated partial thromboplastin time (aPTT) > 150 s, a fibrinogen of
      0.4 g/l, and fibrinogen degradation products < 1 microg/ml. He was given 300 U of
      factor IX concentrate (containing factors II and X) and 1 mg of vitamin K
      intravenously. Forty-five minutes later, clotting tests showed a PT of 24 s, an
      aPTT of 31 s and a fibrinogen of 2.6 g/l. The patient was found to be deficient
      in all the vitamin K-dependent factors: factors II, VII, IX and X, protein C and
      protein S. A 14-base deletion was found in intron 1 (bases 1056-1069) of the
      gamma-carboxylase gene. The patient and his elder sister were homozygous for this
      deletion, whereas both parents were heterozygous. The deletion destroys a reverse
      palindromic sequence (TTGAGGCAA) of the type often associated with cis-acting
      elements. Our results suggest that this element may be involved in the regulation
      of gamma-carboxylase expression. Expression studies are being completed so that
      this region can be definitively ascribed as a cis-acting element involved in gene
      regulation.

PMID- 14567540
TI  - vCJD screening and its implications for transfusion--strategies for the future?
AB  - It remains unclear whether Creutzfeldt Jakob disease (CJD) can be transmitted by
      blood products. Peripheral blood infectivity is demonstrable in experimental
      animal transmissible spongiform encephalopathy models and has been transmitted
      via blood transfusion. However, in man, epidemiological case control, lookback
      and surveillance studies have failed to demonstrate any evidence of sporadic CJD
      transmission by blood transfusion. It cannot be assumed that variant CJD is not
      transmissible in this way because it is a different strain of disease, which is
      known to involve peripheral lymphoid tissues. There is no immune response to
      PrP(Sc) (pathogenic isoform of cellular prion protein PrP(C)) and no nucleic acid
      associated with infectivity has been identified; standard serological and
      molecular assays are therefore inapplicable. Surrogate markers for cerebral
      damage are unlikely to be useful for preclinical screening because they reflect
      the breakdown of the blood-brain barrier in advanced neurological disease. Alpha
      haemoglobin stabilizing factor may provide a surrogate marker during the
      incubation phase. Most approaches to PrP(Sc) discrimination are based on the
      physicochemical characteristics of PrP(Sc); some are now approaching the
      specificity and sensitivity required. However, their validation and potential
      impact on the donor base remain to be resolved.

PMID- 14567539
TI  - Factor XI deficiency--from molecular genetics to clinical management.
AB  - Factor XI (FXI) deficiency is a rare bleeding disorder, but is known to occur
      more frequently in a number of well-defined populations. FXI deficiency is most
      notable for its variable clinical phenotype. The FXI gene is located at the
      distal end of the long arm of chromosome 4 and encodes a 607 amino acid mature
      protein, which is a zymogen for a serine protease. Although the serine protease
      domain is similar to that of many other coagulation factors, the heavy chain
      differs in that it contains four tandem Apple domains. FXI is also unique in that
      it exists as a homodimer, with this dimerization appearing essential for normal
      function. A total of 39 different FXI mutations have been identified to date,
      affecting both the catalytic and Apple domains. This article will review the
      molecular genetics of FXI deficiency with particular focus on the implications of
      these findings for the clinical management of this condition. The potential
      utility of alternatives to plasma-derived FXI concentrate, such as recombinant
      factor VIIa (rFVIIa, NovoSeven) will also be explored.

PMID- 14567541
TI  - Characterization of thrombin activatable fibrinolysis inhibitor in normal and
      acquired haemostatic dysfunction.
AB  - Thrombin activatable fibrinolysis inhibitor (TAFI) is a carboxypeptidase B-like
      proenzyme, which is synthesized in the liver and circulates in the blood at a
      concentration of about 275 nmol/l. Once activated, by thrombin or plasmin, TAFI
      down regulates fibrinolysis, slowing clot lysis by cleaving the C-terminal lysine
      and arginine residues from partially degraded fibrin. Thrombomodulin enhances
      thrombin activation of TAFI by more than 1000-fold, suggesting that the thrombin
      thrombomodulin complex is the physiological activator of TAFI. Activated protein
      C can up-regulate fibrinolysis by limiting the activation of TAFI via the
      attenuation of thrombin production. While impairment of fibrinolysis may
      predispose to thrombosis, excessive fibrinolysis may result in a bleeding
      tendency. In acquired coagulopathies, TAFI antigen levels are reduced in patients
      with disseminated intravascular coagulation. In focusing on women with major post
      partum haemorrhage requiring blood transfusion, a significant reduction in TAFI
      levels is observed. The precise degree of TAFI activation is currently being
      characterized using new and more specific assays. The resulting data may provide
      insight into therapeutic options to treat post-partum haemorrhage, which is
      associated with significant morbidity.

PMID- 14567543
TI  - Kinetic studies on the inhibition of GABA-T by gamma-vinyl GABA and taurine.
AB  - Gamma-aminobutyric acid transaminase (GABA-T, EC 2.6.1.19) is a pyridoxal
      phosphate (PLP) dependent enzyme that catalyzes the degradation of gamma
      aminobutyric acid. The kinetics of this reaction are studied in vitro, both in
      the absence, and in the presence of two inhibitors: gamma-vinyl GABA (4-aminohex
      5-enoic acid), and a natural product, taurine (ethylamine-2-sulfonic acid). A
      kinetic model that describes the transamination process is proposed. GABA-T from
      Pseudomonas fluorescens is inhibited by gamma-vinyl GABA and taurine at
      concentrations of 51.0 and 78.5 mM. Both inhibitors show competitive inhibition
      behavior when GABA is the substrate and the inhibition constant (Ki) values for
      gamma-vinyl GABA and taurine were found to be 26 +/- 3 mM and 68 +/- 7 mM
      respectively. The transamination process of alpha-ketoglutarate was not affected
      by the presence of gamma-vinyl GABA, whereas, taurine was a noncompetitive
      inhibitor of GABA-T when alpha-ketoglutarate was the substrate. The inhibition
      dissociation constant (Kii) for this system was found to be 96 +/- 10 mM. The
      Michaelis-Menten constant (Km) in the absence of inhibition, was found to be 0.79
      +/- 0.11 mM, and 0.47 +/- 0.10 mM for GABA and alpha-ketoglutarate respectively.

PMID- 14567542
TI  - Simplified digitalis-like compounds acting on Na(+), K(+)-ATPase.
AB  - Digitalis compounds are used in the treatment of congestive heart failure as
      positive inotropic agents; their action is mainly due to the inhibition of
      Na(+),K(+)-ATPase. A well-known drawback is their arrhythmogenic potential.
      Attempts to find safer digitalis-like compounds by means of molecular
      simplifications of the typical 5beta,14beta-steroidal skeleton, which appeared in
      the medicinal chemistry literature from 1990 until 2002, are briefly reviewed.
      Several novel achievements were obtained in order to better understand the
      requisites of the digitalis binding site on Na(+), K(+)-ATPase. Only minor
      simplification, such as cleavage of the D ring of the digitalis skeleton, could
      preserve the desired inotropic activity, while highly simplified digitalis-like
      compounds failed to give sufficiently high inotropic potency, even in the
      presence of a powerful pharmacophore, such as the O-aminoalkyloxime group.

PMID- 14567544
TI  - Carbonic anhydrase inhibitors: X-ray crystallographic structure of the adduct of
      human isozyme II with the perfluorobenzoyl analogue of methazolamide.
      Implications for the drug design of fluorinated inhibitors.
AB  - The X-ray crystal structure for the adduct of human carbonic anhydrase (hCA) II
      with 4-methyl-5-perfluorophenylcarboximido-delta2-1,3,4-thiadiazoline-2
      sulfonamide (PFMZ), a topically acting antiglaucoma sulfonamide, has been
      resolved at a resolution of 1.8 A. This compound is almost 10 times more
      effective as a hCA II inhibitor (KI of 1.5 nM) compared to the lead molecule,
      methazolamide, a clinically used drug (KI of 14 nM). Its binding to the enzyme
      active site is similar to that of other sulfonamide inhibitors, considering the
      interactions of the sulfonamide zinc anchoring group and thiadiazoline ring
      contacts, but differs considerably when the perfluorobenzoylimino fragment of the
      molecule is analyzed. Indeed, several unprecedented strong hydrogen bonds
      involving the imino nitrogen, carbonyl oxygen, a fluorine atom in the ortho
      position of the inhibitor, and two water molecules, as well as Gln 92 of the
      enzyme active site were seen. A stacking interaction of the perfluorophenyl ring
      of the inhibitor and the aromatic ring of Phe 131 was also observed for the first
      time in a CA-sulfonamide adduct. All these findings prove that more potent CA
      inhibitors incorporating perfluoroaryl/alkyl tails may be designed, with
      potentially improved antiglaucoma properties, in view of the new types of
      interactions seen here between the enzyme and the perfluorobenzoylated analogue
      of methazolamide.

PMID- 14567545
TI  - Discovery and evaluation of terephthalic acid derivatives as potent alpha4beta1
      integrin antagonists.
AB  - Terephthalic acid based derivatives containing beta- and gamma-amino acid
      residues were prepared as antagonists of the leukocyte cell adhesion process that
      is mediated through the interaction of the very late antigen 4 (VLA-4) and the
      vascular cell adhesion molecule 1 (VCAM-1). The compounds 2, 10-12, 14, and 16-17
      inhibited the adhesion in a cell based assay in the low and sub micromolar range.

PMID- 14567546
TI  - Cytotoxic mannich bases of 1-arylidene-2-tetralones.
AB  - Various 1-arylidene-2-tetralones 1 had been shown previously to possess moderate
      cytotoxic properties unaccompanied by murine toxicity. The objective of the
      present investigation was to undertake different molecular modifications of
      representative members of series 1 with a view to discerning those structural
      features leading to increased potencies. All compounds were evaluated using human
      Molt 4/C8 and CEM T-lymphocytes as well as murine P388 and L1210 leukemic cells.
      The Mannich bases 2, 4, 5 and 7 possessed increased potencies compared to the
      corresponding unsaturated ketones 1 and in general were potent cytotoxics having
      IC50 values in the 0.2-10 microM range. QSAR using the cytotoxicity data for 2a-e
      suggested that potency was positively correlated with the size of the
      substituents in the arylidene aryl ring. Compounds 2a-f were evaluated using a
      panel of approximately 53 human tumour cell lines and, when all cell lines were
      considered, were more potent than the reference drug melphalan. In particular,
      marked antileukemic activity was displayed. Molecular modeling was utilized in
      order to evaluate whether the shapes of the different compounds contributed to
      the varying potencies observed. Representative compounds demonstrated minimal or
      no inhibiting properties towards human N-myristoyltransferase (NMT) and did not
      bind to calf thymus DNA. This study has revealed a number of unique lead
      molecules as candidate anti-neoplastic agents serving as prototypes for future
      development.

PMID- 14567547
TI  - 3,5-bis(phenylmethylene)-1-(N-arylmaleamoyl)-4-piperidones: a novel group of
      cytotoxic agents.
AB  - A series of novel 3,5-bis(phenylmethylene)-1-(N-arylmaleamoyl)-4-piperidones 3
      have been synthesized which displayed potent cytotoxicity towards human Molt 4/C8
      and CEM T-lymphocytes as well as murine P388 and L1210 leukemic cells. In
      contrast, the related N-arylmaleamic acids 4 possessed little or no cytotoxicity
      in these four screens. Molecular modeling revealed certain interplanar and bond
      angles and interatomic distances which were perceived to contribute to the
      observed bioactivity as well as providing suggestions for future structural
      modifications of the piperidones 3. Evaluation of representative compounds in
      series 3 and 4 on the activity of human N-myristoyltransferase revealed that, at
      the maximum concentration utilized, namely 250 microM, only weak inhibiting
      properties were displayed by some of the compounds in series 4. Various members
      of series 3 and 4 were well tolerated in mice.

PMID- 14567548
TI  - Carbonic anhydrase inhibitors. Inhibition of cytosolic isozymes I and II and
      transmembrane, cancer-associated isozyme IX with lipophilic sulfonamides.
AB  - A series of new compounds was obtained by reaction of aromatic/heterocyclic
      sulfonamides incorporating amino groups with N,N-diphenylcarbamoyl chloride and
      diphenylacetyl chloride. These sulfonamides were assayed for the inhibition of
      three carbonic anhydrase (CA, EC 4.2.1.1) isozymes: the cytosolic CA I and CA II,
      and the transmembrane, cancer-associated isozyme CA IX. Good inhibitors against
      all these isoforms were detected, and the inhibition profile of the newly
      investigated isozyme IX was observed to be different from that of the cytosolic
      isozymes, I and II. This may lead to the development of novel anticancer
      therapies based on the selective inhibition of CA IX.

PMID- 14567549
TI  - Monoamine oxidase inhibitory properties of optical isomers and N-substituted
      derivatives of 4-methylthioamphetamine.
AB  - (+/-)-4-Methylthioamphetamine (MTA) was resolved into its enantiomers, and a
      series of N-alkyl derivatives of the parent compound, as well as its alpha-ethyl
      analogue, were prepared. The monoamine oxidase (MAO) inhibitory properties of
      these substances were evaluated in vitro, using a crude rat brain mitochondrial
      suspension as the source of enzyme. All compounds produced a selective,
      reversible and concentration-related inhibition of MAO-A. (+)-MTA proved to be
      the most potent inhibitor studied, while all the other derivatives were less
      active than the parent compound, with (-)-MTA being about 18 times less potent
      than the (+) isomer. The analysis of structure-activity relationships indicates
      that the introduction of alkyl substituents on the amino group of MTA leads to a
      reduction in the potency of the derivatives as MAO-A inhibitors, an effect which
      increases with the size of the substituent.

PMID- 14567550
TI  - Presence of fatty acid synthase inhibitors in the rhizome of Alpinia officinarum
      hance.
AB  - The galangal (the rhizome of Alpinia officinarum, Hance) is popular in Asia as a
      traditional herbal medicine. The present study reports that the galangal extract
      (GE) can potently inhibit fatty-acid synthase (FAS, E.C.2.3.1.85). The inhibition
      consists of both reversible inhibition with an IC50 value of 1.73 microg dried
      GE/ml, and biphasic slow-binding inactivation. Subsequently the reversible
      inhibition and slow-binding inactivation to FAS were further studied. The
      inhibition of FAS by galangin, quercetin and kaempferol, which are the main
      flavonoids existing in the galangal, showed that quercetin and kaempferol had
      potent reversible inhibitory activity, but all three flavonoids had no obvious
      slow-binding inactivation. Analysis of the kinetic results led to the conclusion
      that the inhibitory mechanism of GE is totally different from that of some other
      previously reported inhibitors of FAS, such as cerulenin, EGCG (epigallocatechin
      gallate) and C75.

PMID- 14567552
TI  - The in vitro and in vivo inhibitory effects of some sulfonamide derivatives on
      rainbow trout (Oncorhynchus mykiss) erythrocyte carbonic anhydrase activity.
AB  - The in vitro and in vivo inhibitory effects of 5-(3alpha, 12alpha-dihydroxy-5
      beta-cholanamido)-1,3,4-thiadiazole-2-sulfonamide (1), 5-(3alpha, 7alpha, 12alpha
      trihydroxy-5-beta-cholanamido)-1,3,4-thiadiazole-2-sulfonamide (2), 5-(3alpha,
      7alpha, 12alpha-triacetoxy-5-beta-cholanamido)-1,3,4-thiadiazole-2-sulfonamide
      (3) and acetazolamide on rainbow trout (Oncorhynchus mykiss) (RT) erythrocyte
      carbonic anhydrase (CA) were investigated. The RT erythrocyte CA was obtained by
      affinity chromatography with a yield of 20.9%, a specific activity of 422.5EU/mg
      protein and a purification of 222.4-fold. The purity of the enzyme was confirmed
      by SDS-PAGE. Inhibitory effects of the sulfonamides and acetazolamide on the RT
      erythrocyte CA were determined using the CO2-Hydratase method in vitro and in
      vivo studies. From in vitro studies, it was found that all the compounds
      inhibited CA. The obtained I50 value for the sulfonamides (1), (2) and (3) and
      acetazolamide were 0.83, 0.049, 0.82 and 0.052 microM, respectively. From in vivo
      studies, it was observed that CA was inhibited by the sulfonamides (1), (2) and
      (3) and acetazolamide.

PMID- 14567551
TI  - Inhibition of alpha, betaI, delta, eta, and zeta protein kinase C isoforms by
      xanthonolignoids.
AB  - The effect of the xanthonolignoids trans-(+/-)-kielcorin C, cis-(+/-)-kielcorin
      C, trans-(+/-)-kielcorin D, trans-(+/-)-isokielcorin D and trans-(+/-)-kielcorin
      E on isoforms alpha, betaI, delta, eta and zeta of protein kinase C (PKC) was
      studied using the yeast phenotypic assay. All the compounds tested revealed an
      effect compatible with PKC inhibition, similar to that exhibited by the well
      established PKC inhibitor chelerythrine, and with differences in their potency
      towards the distinct isoforms tested, being, in general, potent inhibitors of the
      atypical PKC isoform (PKC-zeta). PKC inhibition caused by these kielcorins was
      confirmed using an in vitro kinase assay. The present study constitutes the first
      attempt to unravel the molecular mechanism of kielcorins activity, and shows that
      xanthonolignoids are a promising group of compounds to investigate for isoform
      selective PKC inhibitors.

PMID- 14567553
TI  - Effects of ascorbic acid and analogs on the activity of testicular hyaluronidase
      and hyaluronan lyase on hyaluronan.
AB  - We have evaluated the inhibition of testicular hyaluronidase and hyaluronan lyase
      by L-ascorbic acid and chemical analogs. We observed that L-ascorbic acid, D
      isoascorbic acid and dehydroascorbic acid inhibited both types of enzymes, but
      showed stronger effects towards hyaluronan lyase. But these compounds were
      observed to degrade the substrate, hyaluronan, by themselves. Of the other
      ascorbic acid analogs tested, saccharic acid inhibited hyaluronan lyase, while
      not affecting the enzymatic activity of testicular hyaluronidase, nor affecting
      the physic-chemical stability of hyaluronan. This is the first compound, to our
      knowledge, to be shown to possess such selective inhibition. Therefore, we
      propose that saccharic acid could serve as a lead compound for the development of
      potent and selective inhibitors of bacterial hyaluronan lyase or of
      polysaccharide lyase enzymes in general as we observed this compound to be
      capable of inhibiting chondroitinase ABC in addition to hyaluronan lyase.

PMID- 14567554
TI  - Does the "hygiene hypothesis" provide an explanation for the high prevalence of
      multiple sclerosis in Sardinia?
AB  - The "hygiene hypothesis" describes a hypothetical scenario in which the balance
      between TH1 (defending host against bacterial and viral infections) and TH2
      (defending against parasitic infections) immune responses is pivotal and in which
      the consequence of reducing the infectious stressors during infancy is increased
      autoimmunity (TH1-mediated) and allergy (TH2-mediated). Many epidemiological
      observations confirm that allergic and autoimmune diseases are significantly
      increased in the "developed" countries and negatively associated with childhood
      infections. However, it has been recently revealed that immune elements
      associated with allergy are extensively involved also in the pathogenesis of
      autoimmune demyelination and that TH2- and TH1-mediated infections ameliorate the
      course of the disease confirming that the allergic root is also responsible for
      the escalation of autoimmune disorders, and both have a common immunological
      denominator. In the Italian island of Sardinia, MS and type-I diabetes
      frequencies have sharply increased in the last decades compared to other
      populations living in the same Mediterranean area. Initial observation led us to
      believe that environmental changes favoured the MS risk rise, thus sustaining the
      hygiene hypothesis. However, data on MS prevalence distribution in this territory
      suggest that other mechanisms than environment have also to be taken into great
      account. Our recent epidemiological studies reveal significant differences in the
      MS prevalence between rural and urban areas within the same province of Sassari
      but, contrarily to what expected from the hygiene hypothesis, MS prevalence is
      significantly higher in rural, genetically "archaic", areas where the
      westernalization process has been less pronounced. On this basis we believe that,
      beside hygiene-related factors, genetics could represent a more relevant
      determinant of Sardinian high susceptibility to MS.

PMID- 14567556
TI  - Anti-extractable nuclear antigens (ENA) antibodies in patients with chronic
      hepatitis C before and after treatment with interferon.
AB  - A high prevalence of serological markers classically associated with autoimmune
      hepatitis or other autoimmune diseases has been reported in patients with chronic
      hepatitis C. However, the prevalence of antibodies to extractable nuclear
      antigens (anti-ENA) are rarely reported in such patients and the effect of
      treatment with interferon (IFN) on their prevalence is not known. In the present
      study, serum samples collected from 44 patients with chronic hepatitis C and 44
      patients with non-hepatitis C virus (HCV) infected liver diseases were tested for
      anti-ENAs (U1 RNP, Sm, Ro/SS-A, La/SS-B and Scl-70) antibodies by enzyme-linked
      immunosorbent assay (ELISA). In 26 patients with chronic hepatitis C who received
      IFN treatment, serum samples were also collected just after completion of IFN
      treatment, and/or at 6-40 months after completion of the treatment, and tested
      for these antibodies. Sixteen (36%) of 44 sera from patients with chronic
      hepatitis C were positive for at least one of the above anti-ENA antibodies,
      whereas only 7 (16%) of 44 sera from patients with non-HCV infected liver
      diseases were positive for such antibodies (p = 0.0290). There was no significant
      difference in the prevalence of each of anti-ENA antibody between men and women.
      Results of anti-ENA antibodies in most IFN-treated patients with chronic
      hepatitis C did not change after treatment. However, in some cases serum anti-U1
      RNP, anti-La/SS-B and anti-Scl-70 became negative or converted to the gray zone
      after completion of IFN treatment regardless of HCV elimination. Our results
      showed that the overall prevalence of anti-ENA antibodies was significantly
      higher in patients with chronic hepatitis C than in those with non-HCV-infected
      liver diseases. However, the disappearance of anti-ENA antibodies after IFN
      treatment in patients with chronic hepatitis C may be due to the immunomodulating
      effects of IFN rather than HCV elimination.

PMID- 14567555
TI  - Yersinia enterocolitica O:3 isolated from patients with or without reactive
      arthritis induces polyclonal activation of B cells and autoantibody production in
      vivo.
AB  - The mechanisms by which arthritis-provoking pathogens such as Yersinia
      enterocolitica interact with the human immune system to produce inflammatory
      synovitis are not well known. One of the immunomodulating mechanisms used against
      these pathogens is the polyclonal activation of lymphocytes. In this study, we
      investigated the extent of the B-lymphocyte activation induced in mice by a
      strain of Y. enterocolitica O:3 (FCF 526) isolated from a patient with arthritis,
      and compared it with two other strains, a virulent one (FCF 397[+]) isolated from
      a patient without arthritis and its plasmidless isogenic pair (FCF397[-]). Also
      we investigated the production of autoantibodies in mice infected with these
      different strains. SPF Swiss mice were infected intravenously with a suspension
      of Y. enterocolitica. Spleen cells were taken on days 7, 14, 21 and 28 after
      infection and the number of cells secreting nonspecific and specific antibodies
      of IgG1, IgG2a, IgG2b, IgG3, IgM and IgA isotypes were determined by the ELISPOT
      technique. The presence of autoantibodies in mouse serum was investigated by the
      dot-blot assay. The pattern of infection of the three bacterial strains were
      almost the same. We observed a general increase in the number of nonspecific Ig
      secreting cells with all three strains, and the greatest increases observed were
      in the IgG2a and IgG3 isotypes. Only a small fraction of the immunoglobulins
      detected were antibacterial, suggesting that the rest resulted from polyclonal B
      cell activation. The strain isolated from the patient with arthritis (FCF526)
      induced the greatest production of autoantibodies, coinciding with the period in
      which the greatest activation of nonspecific B lymphocytes was seen. There were
      no signs of arthritis or inflammation in the joints of the infected animals.
      Based on our results, we were unable to determine whether there is an association
      between the arthritogenic capability of Y. enterocolitica and polyclonal
      activation of B cells.

PMID- 14567557
TI  - HK-ATPase expression in the susceptible BALB/c and the resistant DBA/2 strains of
      mice to autoimmune gastritis.
AB  - Neonatal thymectomy (NTx) in mice induces a group of alterations in the immune
      system homeostasis that results in the development of a variety of organ-specific
      autoimmune diseases such as gastritis, thyroiditis, oophoritis and orchitis.
      Given the importance of self-antigen expression in thymus for the control of
      autoreactive cells and generation of regulatory cells, we have compared the
      expression of parietal cell antigen in two strains of mice with the same H-2:
      BALB/c (susceptible to develop gastritis after NTx) and DBA/2 (resistant). We
      detected mRNA of HK-ATPase alpha and beta chains in day 1 thymi of both strains.
      Fifty percent of BALB/c mice presented mRNA levels similar to DBA/2. However,
      lower mRNA levels were found in the remaining BALB/c mice that may correspond to
      those that would develop AIG after NTx. Since the presence of the antigen in
      periphery is also necessary for the induction of regulatory cells, we have
      compared both strains observing in day 1 stomachs from resistant DBA/2 strain, a
      significantly higher content of positive cells for HK-ATPase subunits than
      stomachs from susceptible BALB/c strain. Also, the presence of antinuclear Abs in
      NTx BALB/c mice makes this model a useful experimental system for analyzing the
      responsible mechanisms breaking the non-specific self-tolerance.

PMID- 14567558
TI  - Elevated IL-10 inhibits GM-CSF synthesis in pulmonary alveolar proteinosis.
AB  - Pulmonary alceolar proteinosis (PAP) is an autoimmune lung disease characterized
      by accumulation of surfactant material within the lung. Autoantibodies to GM-CSF
      as well as high levels of IL-10 are also found in the lungs in PAP. Previous
      studies suggest that treatment with recombinant GM-CSF is beneficial for patients
      with low levels of GM-CSF antibodies. The role of IL-10 in PAP, however, is
      unknown and the hypothesis that IL-10 may affect PAP GM-CSF synthesis has not
      been addressed. The current findings show that GM-CSF secretion is significantly
      compromised in PAP bronchoalveolar lavage (BAL) cells compared to controls, but
      surprisingly, GM-CSF mRNA levels are elevated. In contrast, IL-10 protein and
      mRNA levels are both highly elevated in PAP. In vitro analysis of GM-CSF
      regulation indicates that both secretion and mRNA levels are sharply reduced by
      IL-10 and increased by anti-IL-10 antibody. The phenomenon of elevated GM-CSF
      mRNA in BAL cells appears not to be due to lack of negative feedback by GM-CSF
      protein. Results suggest that in PAP, GM-CSF synthesis is deficient and
      associated with negative regulation by IL-10. Furthermore, IL-10 gene expression
      becomes even more elevated in patients who do not respond to recombinant GM-CSF
      therapy and have high anti-GM-CSF titers. Based on these observations, we
      hypothesize that IL-10 may be an indicator of PAP clinical response to GM-CSF
      therapy.

PMID- 14567559
TI  - Lymphocyte subpopulations, oxidative burst and apoptosis in peripheral blood
      cells of patients with multiple sclerosis-effect of interferon-beta.
AB  - At present, the most efficient therapeutical treatment of multiple sclerosis (MS)
      is achieved by IFN-beta. However, its in vivo effects remain incompletely
      understood. If applied parenterally, the hydrophobic IFN-beta acts primarily on
      blood cells with probable selectivity for functionally different lymphocyte
      subpopulations, monocytes and granulocytes. We have investigated the expression
      of the activation marker interleukin-2 receptor-alpha (CD25) on CD3+ T cells,
      CD19+ B cells, foetal-type gamma(delta)+CD3+ T cells and foetal-type CD5+CD19+ B
      cells of the peripheral blood. In addition, the oxidative burst activity and
      apoptosis have been determined in mononuclear and polymorphonuclear blood cells,
      respectively. The study accompanied a phase III trial with IFN-beta1b (BETAFERON,
      Schering). Two groups of MS patients with relapsing-remitting course of the
      disease have been investigated at 8 time points (days 0, 5, 15, 31, 60, 90, 180
      and 270 after starting therapy): (1) verum group (n = 8) with application of 8
      Mill. units IFN-beta1 b every other day, and (2) placebo group (n = 4) with
      application of placebo for 3 months and therapy as in (1) from day 90 onward. The
      main results were: (1) Activated T cells decreased until day 180 in the verum
      group and return thereafter to pre-treatment values, whereas in the placebo group
      the values remained relatively stable over the whole observation period. (2)
      Activated B cells increased between days 90 and 270 in both groups, i.e. after
      verum application in both groups. (3) Foetal-type B cells were more activated
      than total B and T cells with increase over time in both groups. (4) Foetal-type
      T cells exerted relatively stable intra-individual levels with generally low CD25
      expression, but punctual CD25 peaks in both groups. (5) The spontaneous oxidative
      burst was higher in lymphocytes, more variable in monocytes and faster increasing
      in granulocytes in the verum group than in the placebo group. (6) Apoptosis of
      mononuclear cells and granulocytes showed similar variations in the verum and
      placebo groups with the exception of a selective increase over time of the
      proportion of granulocytes undergoing induced apoptosis in the verum group. It is
      concluded that IFN-beta has the following main effects on the immune system of MS
      patients: (1) the T cell immunity is systemically and reversibly suppressed, (2)
      the foetal-type lymphocytes, which are responsible for the first line of defence
      of infections, are stimulated in the long range, (3) the oxidative burst activity
      is increased in lymphocytes and granulocytes and instable in monocytes, and (4)
      the inducibility of apoptosis in granulocytes is increased. Re-examination of the
      altered blood cell parameters after long-term IFN-beta therapy is warranted.

PMID- 14567560
TI  - Elevated levels of anti-Helicobacter pylori antibodies in Henoch-Schonlein
      purpura.
AB  - OBJECTIVE: Henoch-Schonlein purpura (HSP) is a systemic vasculitis characterized
      by IgA-containing deposits in the skin, joints, gastrointestinal mucosa and
      glomeruli. HSP is much rarer in adults than in children. Among a number of other
      pathogenic factors, Helicobacter pylori (Hp) has recently been implicated in the
      gastrointestinal and extra-gastrointestinal manifestations underlying HSP. We
      aimed at studying the occurrence of Hp infections in 11 adult HSP patients with
      appearance in our clinical practice in the last 5 years. METHODS: Eleven adult
      HSP and 20 healthy adult patients were recruited for this study. Anti-Hp IgG and
      IgA antibodies were assessed in sera of HSP patients with active (n = 5) and
      remittent disease (n = 6) and healthy controls (n = 20) in the context of
      clinical symptoms, endoscopic evaluation, as well as routine and immunolaboratory
      observations. Concurrent Hp infection was confirmed by urease test and histology.
      RESULTS: Anti-Hp antibodies were present in 10/11 of HSP patients, and 11/20 of
      healthy controls. However, only 4/11 HSP patients had concurrent Hp infection as
      confirmed by urease test and/or histology. In the healthy controls the actual Hp
      infection was detectable in 9/20 cases. Patients in the acute phase had
      significantly higher levels of anti-Hp IgG compared to healthy controls (86.0 +/-
      32.0 versus 25.5 +/- 28.5 U/ml, p < 0.05). In contrast, anti-Hp IgA/IgG ratios
      were significantly higher in the remitting phase compared to the control group
      (3.1 +/- 1.8 versus 0.8 +/- 0.5 ratio, p < 0.05). Among other immunolaboratory
      markers, serum CRP, circulating IgA and serum tumor necrosis factor-alpha levels
      were significantly increased in acute patients compared to healthy group results
      (45.3 +/- 22.7 versus 4.8 +/- 3.5 mg/l, p < 0,05); (58.9 +/- 18.2 versus 25.2 +/-
      6.4pg/ml, p < 0,05); (5.5 +/- 1.1 versus 2.4 +/- 1.2 g/l; respectively, p <
      0.05). CONCLUSIONS: Hp infection may be associated with the development and
      progression of HSP. IgG antibodies to Hp may be present mostly in acute HSP,
      while IgA antibodies may be involved in sustaining gastrointestinal symptoms
      underlying the chronic phase of the disease.

PMID- 14567561
TI  - Exon-1 polymorphism of ctla-4 gene in Iranian patients with Graves' disease.
AB  - Polymorphisms in ctla-4 gene have been shown to be associated with the Graves'
      disease (GD) susceptibility in different populations in the world. This study was
      undertaken to disclose the probable association of exon-1 polymorphism of ctla-4
      with GD in Iranian patients. A49G polymorphism was investigated in 90 patients
      and 90 age/sex matched normal healthy controls, using PCR-SSCP and PCR-RFLP
      methods. Frequencies of AA, AG and GG genotypes among patients were found to be
      21 (23.3%), 49 (54.5%) and 20 (22.2%) while these frequencies among healthy
      controls were 30 (33.3%), 53 (58.9%) and 7(7.8%), respectively. A significant
      increase of GG genotype and G allele was observed in patients (p = 0.012 and p =
      0.025). In conclusion, consistent with the results of most other studies, the
      presence of a G allele in position 49 of ctla-4 exon-1 is associated with
      susceptibility to GD in Iranian population.

PMID- 14567562
TI  - Induction of T-cell tolerance in a patient with idiopathic thrombocytopenic
      purpura by single injection of humanized monoclonal antibody to CD40 ligand.
AB  - Normal B cells can be induced to express immune costimulatory molecules by
      activated T cells, and activated CD4 T cells can express CD40 ligand, a molecule
      that can engage CD40 on the B-cell surface. CD40-CD40 ligand interaction plays an
      important role in the pathology of certain autoimmune diseases. We report a
      patient with chronic idiopathic thrombocyopenic purpura (ITP) who was effectively
      treated with a single injection of humanized monoclonal antibody to CD40 ligand
      (E6040). The patient was refractory to steroid therapy, and had baseline platelet
      counts below 30 x 10(9)/l during the 3-month period before antibody treatment.
      The patient's platelet counts have increased to more than 100 x 10(9)/l long-term
      after E6040 administration. Platelet-associated IgG was decreased with
      thrombocytosis. Compared with the initial period of E6040 administration, the
      number of anti-GPIIb/IIIa antibody-producing B cells decreased, and proliferative
      response of autoreactive T cells to GPIIb/IIIa was also improved. A single
      injection of humanized monoclonal antibody to CD40 ligand may induce T-cell
      tolerance in patients with ITP.

PMID- 14567563
TI  - Protecting the privacy of our patients' health information.

PMID- 14567564
TI  - Psychosocial support for patients in pediatric oncology: the influences of
      parents, schools, peers, and technology.
AB  - The diagnosis and treatment of pediatric cancer can be associated with profound
      psychosocial changes in the life of young patients. Although nurses, physicians,
      and other health care professionals are important sources of support,
      psychosocial support is also available through parents, schools, and peers. This
      article presents a review of the literature on how parents, schools, and peers
      affect the coping and adjustment of young patients with cancer and critically
      reviews interventions directed at improving functioning in these areas. Special
      attention is paid to recent interventions that exploit technology such as video
      games, CD-ROMs, and the Internet to provide creative new forms of support for
      patients in pediatric oncology. Existing research on both technological and
      interpersonal forms of intervention and support shows promising results, and
      suggestions for further study are provided.

PMID- 14567565
TI  - Communication issues faced by parents who have a child diagnosed with cancer.
AB  - Twenty-nine parents of children who had been diagnosed with various cancers were
      interviewed through long, semistructured interviews conducted via telephone by a
      mother whose daughter once had cancer. Parents usually began their narratives of
      the defining moments in the months, weeks, or days prior to the diagnosis. The
      authors report on parents' views about one of the defining moments in the
      stories. At the first level, we call this "communication issues" and include the
      following topics: communication at diagnosis, contradictions and confusion,
      getting the "right" amount of information, good and poor communication, feeling
      listened to, and errors in medical information. At another level, the way that
      parents talk about communications issues reflects an underlying paradox that
      parents whose children have cancer face: They are and feel responsible for their
      children, and yet they often lack knowledge, authority, and power in their
      dealings with the health care system and its medical care providers.

PMID- 14567567
TI  - Barrier efficacy of woven and nonwoven fabrics used for protective clothing:
      predictive models.

PMID- 14567566
TI  - Quality of life among childhood leukemia patients.
AB  - The purpose of this qualitative descriptive study was to allow childhood leukemia
      patients to describe their quality of life (QoL) in their own words. These
      personal accounts provide an opportunity for health care personnel to understand
      the impact that leukemia has on these children. A total of 13 children in three
      focus group interviews participated. They ranged in age from 5 to 9 years and
      were either off therapy or had completed at least 6 months of treatment. Four
      semistructured interview questions were used to guide the interviews. Each
      question related to a domain identified in previous research as having an effect
      on QoL. Thus, the areas explored in this study were (a) physical well-being and
      symptoms, (b) psychological well-being, (c) social well-being, and (d) spiritual
      well-being. Five themes were identified: (a) fatigue, (b) the effect on
      activities, (c) medication and treatment effects, (d) relationship changes, and
      (e) hair loss.

PMID- 14567568
TI  - Bovine red blood cell ghost cholinesterase as a monitoring standard.

PMID- 14567569
TI  - Toxic effects of textile printing industry effluents on liver and testes of
      albino rats.

PMID- 14567570
TI  - Evaluation of estrogenic activity and effect of endosulfan on biochemical
      constituents in ovariectomized (OVX) Swiss albino mice.

PMID- 14567571
TI  - 1-Hydroxypyrene as a biomarker for fish exposure to polycyclic aromatic
      hydrocarbons.

PMID- 14567572
TI  - Pseudomonad strains exhibiting high level Cr(VI) resistance and Cr(VI)
      detoxification potential.

PMID- 14567573
TI  - Developmental toxicity of copper, chromium, and aluminum using the shrimp embryo
      teratogenesis assay: Palaemonid with artificial seawater.

PMID- 14567574
TI  - Effects of exposure to copper and malathion on metallothionein levels and
      acetylcholinesterase activity of the mussel Mytilus edulis and the clam Macoma
      balthica from the northern Baltic Sea.

PMID- 14567575
TI  - Effects of fipronil and chlorpyrifos on endocrine-related endpoints in female
      grass shrimp (Palaemonetes pugio).

PMID- 14567576
TI  - Linkages between population demographics and municipal effluent estrogenicity.

PMID- 14567577
TI  - Impacts of Fenholloway River water on invertebrate biodiversity and growth of
      Daphnia magna.

PMID- 14567578
TI  - DT-diaphorase [NAD(P)H: (quinone acceptor) oxidoreductase] in Gammarus pulex:
      kinetics and some biochemical properties.

PMID- 14567579
TI  - Toxicity of cadmium, lead, and zinc to larval stages of Lithodes santolla
      (Decapoda, Anomura).

PMID- 14567580
TI  - Toxic effects of dimethoate and carbaryl pesticides on reproduction and related
      enzymes of the freshwater snail Lymnaea acuminata.

PMID- 14567581
TI  - Chlorobenzenes in snow crab (Chionoectes opilio): time-series monitoring
      following an accidental release.

PMID- 14567582
TI  - Pollution by mercury, arsenic, lead, chromium, cadmium, and polycyclic aromatic
      hydrocarbons of fish and mussels from the Gulf of Naples, Italy.

PMID- 14567583
TI  - Histopathological changes in the gastrointestinal tract of fish, Puntius
      gonionotus, fed on dietary cadmium.

PMID- 14567584
TI  - Mercury levels in the green-lipped mussel Perna viridis (Linnaeus) from the west
      coast of peninsular Malaysia.

PMID- 14567585
TI  - Contamination of coral reef by heavy metals along the Egyptian Red Sea coast.

PMID- 14567586
TI  - Toxicity of sulfonylurea herbicides to the green alga Scenedesmus vacuolatus:
      predictability of combination effects.

PMID- 14567587
TI  - Toxicity of 21 herbicides to the green alga Scenedesmus quadricauda.

PMID- 14567588
TI  - Toxicity of dibutyl phthalate to algae.

PMID- 14567589
TI  - Effects of nutrients and salinity on the algal assay using Pseudokirchneriella
      subcapitata (Korshikov) Hindak.

PMID- 14567590
TI  - Copper, manganese, lead, and zinc concentrations on Eucalyptus sp. leaves in a
      small coastal town.

PMID- 14567591
TI  - Biodegradation of polycyclic aromatic hydrocarbons in sludge.

PMID- 14567592
TI  - Factors influencing formation of trihalomethanes in swimming pool water.

PMID- 14567593
TI  - Elution of 1,4-dioxane from waste landfill sites.

PMID- 14567594
TI  - Chemically-enhanced phytoextraction of cadmium-contaminated soils using wheat
      (Triticum aestivum L.).

PMID- 14567595
TI  - Neurosurgical education: the "other" competencies. The 2003 presidential address.
AB  - In his 2003 Presidential Address to the American Association of Neurological
      Surgeons, Dr. Heros discusses his personal additions to the six basic
      competencies for which all neurosurgical residents must be tested. The basic
      competencies are as follows: 1) patient care; 2) medical knowledge; 3) practice
      based learning and improvement; 4) interpersonal and communication skills; 5)
      professionalism; and 6) system-based practice. To these, Dr. Heros proposes to
      add six supplemental competencies: 1) intellectual honesty, which involves frank
      discussions about patient complications and admissions of the physician's
      frailties; 2) scholarship--the art and science of medicine, which recognizes the
      value of evidence-based medicine but does not discount knowledge derived from
      experience; 3) practicing in a hyperlegalistic society, which involves tailoring
      informed consent to fit individual patients' circumstances; 4) time- and cost
      efficient practices, in which the physician strives to conserve time and
      resources by forgoing testing that is not strictly necessary, doing only what is
      needed to return patients to wellness; 5) approach to patients, which entails
      acknowledging and respecting the dignity of all patients; and 6) pride in being a
      neurosurgeon, which carries a sense of elitism without arrogance.

PMID- 14567596
TI  - Axillary nerve repair in 99 patients with 101 stretch injuries.
AB  - OBJECT: The purpose of this paper was to analyze outcomes in patients at the
      Louisiana State University Health Sciences Center (LSUHSC) who presented with
      contusion-stretch injuries to the axillary nerve. These injuries resulted from
      shoulder injury either with or without fracture/dislocation. Although recovery of
      deltoid function can occur spontaneously, this was not always the case. METHODS:
      Severe deficits persisting for several months led the patients to undergo
      surgery. Operative categories included isolated axillary palsy (56 procedures),
      combined axillary and suprascapular palsies (11 procedures), axillary and radial
      palsies (14 procedures), and axillary palsy with another deficit, usually
      infraclavicular plexus loss (20 procedures). Deltoid function was evaluated pre-
      and postoperatively by applying the LSUHSC grading system. An anterior
      infraclavicular approach was usually followed during surgery, but in three
      patients an additional posterior approach was used. Axillary lesions usually
      began in the proximal portion of the posterior cord. Although several patients
      had distraction of the nerve, lesions in continuity were found in more than 90%
      of cases. Intraoperative nerve action potential (NAP) recordings were performed
      to determine the need for resection. Most repairs were made using grafts,
      although in three patients with relatively focal lesions suture was used. When an
      NAP was recorded across the lesion and neurolysis was performed, recovery was
      judged to be a mean Grade 4 according to the LSUHSC in 30 cases. Recovery
      following suture repairs was a mean Grade 3.8, whereas recovery after 66 graft
      repairs was a mean Grade 3.7. In cases in which suprascapular palsies were
      associated with axillary injuries, the former recovered but the latter did not
      necessarily do so without surgery. If the radial nerve was also injured, recovery
      of the triceps and brachioradialis muscles and wrist extension was usually
      obtained, but it was far more difficult to reverse the loss of finger and thumb
      extension. Although few in number, complications did occur and they are
      important. CONCLUSIONS: Operative exploration of axillary contusion-stretch
      lesions is worthwhile in carefully selected cases. If indicated by inspection and
      intraoperative electrical studies, nerve repair can lead to useful function.

PMID- 14567597
TI  - A genealogical assessment of heritable predisposition to aneurysms.
AB  - OBJECT: This study was conducted to investigate the familial and genetic
      contribution to intracranial, abdominal aortic, and all other types of aneurysms,
      and to define familial relationships among patients who present with the
      different aneurysm types. METHODS: The authors used a unique Utah resource to
      perform population-based analysis of the familial nature of aneurysms. The Utah
      Population Data Base is a genealogy of the Utah population dating back eight
      generations, which is combined with death certificate data for the state of Utah
      dating back to 1904. Taking into account the genetic relationships among all
      aneurysm cases derived from this resource, the authors used a previously
      published method to estimate the familiality of different aneurysm types. Using
      internal, birth-cohort-specific rates of disease calculated from the database,
      they estimated relative risks by comparing observed to expected rates of aneurysm
      incidence in defined sets of relatives of probands. CONCLUSIONS: Each of the
      three aneurysm types investigated showed significant evidence for a genetic
      component. Relatives of patients with intracranial aneurysms do not appear to be
      at increased risk for abdominal or other lesions, but relatives of patients with
      abdominal aortic aneurysms appear to be at increased risk for other types of
      these lesions.

PMID- 14567598
TI  - Factors associated with the development of vasospasm after planned surgical
      treatment of aneurysmal subarachnoid hemorrhage.
AB  - OBJECT: The goal of this study was to determine factors associated with the
      development of symptomatic vasospasm among patients with aneurysmal subarachnoid
      hemorrhage (SAH) who participated in the randomized, double-blind, placebo
      controlled trials of tirilazad between 1991 and 1997. METHODS: Data obtained from
      3567 patients entered into trials of tirilazad were analyzed using uni- and
      multivariate logistic regression to determine factors that predict the
      development of symptomatic vasospasm. Symptomatic vasospasm was defined by
      clinical criteria accompanied by laboratory- and radiologically determined
      exclusion of other causes of neurological deterioration. Transcranial Doppler
      ultrasonographic and/or angiographic confirmation was not required. In these
      patients, the aneurysms were scheduled to be treated surgically, and no patient
      undergoing endovascular treatment was included. A multivariate analysis showed
      that factors significantly associated with vasospasm were age 40 to 59 years,
      history of hypertension, worse neurological grade, thicker blood clot on the
      cranial computerized tomography (CT) scan obtained on hospital admission, larger
      aneurysm size, presence of intraventricular hemorrhage (IVH), prophylactic use of
      induced hypertension, and not participating in the first European tirilazad
      study. CONCLUSIONS: Symptomatic vasospasm was associated with the amount of SAH
      on the CT scan, the presence of IVH, and the patient's neurological grade. The
      association with patient age may reflect alterations in vessel reactivity
      associated with age. A history of hypertension may render the brain more
      susceptible to symptoms from vasospasm. The explanation for the relationships
      with aneurysm size, use of prophylactic induced hypertension, and the particular
      study is unclear.

PMID- 14567599
TI  - Comparison of periprocedure complications resulting from direct stent placement
      compared with those due to conventional and staged stent placement in the basilar
      artery.
AB  - OBJECT: Medically refractory, symptomatic atherosclerotic disease of the basilar
      artery (BA) portends a poor prognosis. Studies have shown morbidity rates
      following placement of stents in these lesions to be quite variable, ranging from
      0 to 30%. The authors review their experience with BA stent placement for severe
      atherosclerotic disease to determine whether an increase in neurological
      morbidity is associated with direct stent placement (that performed without
      predilation angioplasty) compared with conventional stent placement (that
      performed immediately after predilation angioplasty) or staged stent placement
      (angioplasty followed > or = 1 month later by stent placement with or without
      repeated angioplasty). METHODS: The authors retrospectively reviewed the medical
      records from a consecutive series of 10 patients who underwent stent placement
      for medically refractory, symptomatic atherosclerotic disease of the BA between
      February 1999 and November 2002. Patient records were analyzed for symptoms at
      presentation, percentage of angiographically visible stenosis, devices used,
      procedure-related morbidity, and clinical and radiographic outcomes. Patients
      with symptomatic intracranial vertebral artery stenosis but without concomitant
      severe (> 50%) BA stenosis were excluded from the study. Four patients were
      treated with direct stent placement, three with a staged procedure (these were
      included in a previous publication), and three with conventional stent placement.
      In the group treated with direct stent placement, a dense quadriparesis developed
      in two patients after the procedure. Computerized tomography or magnetic
      resonance imaging revealed infarction of the ventral pons in these patients. In
      the staged stent placement group, no permanent neurological complications
      occurred after the procedure and, in the conventional stent placement group, one
      of three patients experienced a neurological complication involving homonymous
      hemianopsia. CONCLUSIONS: Direct stent placement in the BA is associated with a
      relatively high complication rate, compared with a staged procedure.
      Complications may result from an embolic shower following disruption of
      atheromatous plaque debris attained using high-profile devices such as stents, as
      demonstrated by the postoperative imaging appearance of acute pontine
      infarctions. Additionally, displacement of debris by the stent into the ostia
      (snowplowing) of small brainstem perforating vessels may be responsible for the
      complications noted. Although direct stent placement in peripheral and coronary
      vessels has been shown to be safe, the authors suggest that direct stent
      placement in the BA should be avoided to minimize the risk of periprocedure
      morbidity.

PMID- 14567600
TI  - Low-dose aspirin prophylaxis and risk of intracranial hemorrhage in patients
      older than 60 years of age with mild or moderate head injury: a prospective
      study.
AB  - OBJECT: The goal of this paper was to investigate a possible relationship between
      the consumption of low-dose aspirin (LDA) and traumatic intracranial hemorrhage
      in an attempt to determine whether older patients receiving prophylactic LDA
      require special treatment following an incidence of mild-to-moderate head trauma.
      METHODS: Two hundred thirty-one patients older than 60 years of age, who arrived
      at the emergency department with a mild or moderate head injury (Glasgow Coma
      Scale [GCS] Scores 13-15 and 9-12, respectively), were included in the study. One
      hundred ten patients were receiving prophylactic LDA (100 mg/day) and these
      formed the aspirin-treated group. One hundred twenty-one patients were receiving
      no aspirin, and these formed the control group. There was no statistically
      significant difference between the two groups with respect to age, sex, mechanism
      of trauma, or GCS score on arrival at the emergency department. Most of the
      patients sustained the head injury from falls (88.2% of patients in the aspirin
      treated group and 85.1% of patients in the control group), and had external signs
      of head trauma such as bruising or scalp laceration (80.9% of patients in the
      aspirin-treated group and 86.8% of patients in the control group). All patients
      underwent similar neurological examinations and computerized tomography (CT)
      scanning of the head. The CT scans revealed evidence of traumatic intracranial
      hemorrhage in 27 (24.5%) patients in the aspirin-treated group and in 31 patients
      (25.6%) in the control group. Surgical intervention was required for five
      patients in each group (4.5% of patients in the aspirin-treated group and 4.1% of
      patients in the control group). A surprising number of the patients who arrived
      with GCS Score 15 were found to have traumatic intracranial hemorrhage, as
      revealed by CT scanning (11.5% of patients in the aspirin-treated group and 16.5%
      of patients in the control group). Surgery, however, was not necessary for any of
      these patients. CONCLUSIONS: There was no statistically significant difference in
      the frequency or types of traumatic intracranial hemorrhage between patients who
      had received aspirin prophylaxis and those who had not. The authors conclude that
      LDA does not increase surgically relevant parenchymal or meningeal bleeding
      following moderate and minor head injury in patients older than 60 years of age.

PMID- 14567601
TI  - Patient age and outcome following severe traumatic brain injury: an analysis of
      5600 patients.
AB  - OBJECT: Increasing age is associated with poorer outcome in patients with closed
      traumatic brain injury (TBI). It is uncertain whether critical age thresholds
      exist, however, and the strength of the association has yet to be investigated
      across large series. The authors studied the shape and strength of the
      relationship between age and outcome, that is, the 6-month mortality rate and
      unfavorable outcome based on the Glasgow Outcome Scale. METHODS: The shape of the
      association was examined in four prospective series with individual patient data
      (2664 cases). All patients had a closed TBI and were of adult age (96% < 65 years
      of age). The strength of the association was investigated in a metaanalysis of
      the aforementioned individual patient data (2664 cases) and aggregate data (2948
      cases) from TBI studies published between 1980 and 2001 (total 5612 cases).
      Analyses were performed with univariable and multivariable logistic regression.
      Proportions of mortality and unfavorable outcome increased with age: 21 and 39%,
      respectively, for patients younger than 35 years and 52 and 74%, respectively,
      for patients older than 55 years. The association between age and both mortality
      and unfavorable outcome was continuous and could be adequately described by a
      linear term and expressed even better statistically by a linear and a quadratic
      term. The use of age thresholds (best fitting threshold 39 years) in the analysis
      resulted in a considerable loss of information. The strength of the association,
      expressed as an odds ratio per 10 years of age, was 1.47 (95% confidence interval
      [CI] 1.34-1.63) for death and 1.49 (95% CI 1.43-1.56) for unfavorable outcome in
      univariable analyses, and 1.39 (95% CI 1.3-1.5) and 1.46 (95% CI 1.36-1.56),
      respectively, in multivariable analyses. Thus, the odds for a poor outcome
      increased by 40 to 50% per 10 years of age. CONCLUSIONS: An older age is
      continuously associated with a worsening outcome after TBI; hence, it is
      disadvantageous to define the effect of age on outcome in a discrete manner when
      we aim to estimate prognosis or adjust for confounding variables.

PMID- 14567602
TI  - Expression of Ki-67 antigen in nonfunctioning pituitary adenomas: correlation
      with growth velocity and invasiveness.
AB  - OBJECT: The cell cycle-dependent nuclear antigen Ki-67 is related to growth
      potential in a variety of tumors. Elevated expression of Ki-67 was previously
      shown in recurrent pituitary adenomas; however, it has remained unclear whether
      this expression is related to the growth velocity or invasive behavior of these
      tumors. The aim of this study was to determine the correlation of Ki-67 antigen
      expression, growth velocity, and invasiveness in nonfunctioning pituitary
      adenomas. METHODS: Between April 1998 and April 2002, 23 patients with
      nonfunctioning pituitary adenomas who had participated in an observation period
      in which multiple computerized tomography and magnetic resonance imaging studies
      had been performed were surgically treated in our department. Tumor volumes were
      assessed using a stereological method based on the Cavalieri principle. The
      growth rate was calculated for each patient. Expression of Ki-67 antigen was
      examined using the monoclonal antibody MIB-1. The assessed growth velocity of the
      adenomas was best described by a linear growth model. The correlation between Ki
      67 expression and growth rate was highly significant. Rapidly growing adenomas (>
      0.07% daily increase in size) were found to have a Ki-67 labeling index (LI)
      exceeding 1.5%, whereas all five adenomas with a very slow growth rate (< 0.02%
      daily increase in size) had a Ki-67 LI lower than 1.5%. No correlation was found
      between the growth rate and the invasive character of the adenomas. CONCLUSIONS:
      Expression of Ki-67 antigen is significantly correlated to the growth velocity of
      pituitary adenomas. Invasive behavior is a feature independent of proliferative
      activity. The extent of Ki-67 expression is helpful for clinical decision making
      and routine assessment of Ki-67 is recommended during the histopathological
      workup of pituitary adenomas.

PMID- 14567603
TI  - Incidence of venous thromboembolism in patients undergoing craniotomy and motor
      mapping for glioma without intraoperative mechanical prophylaxis to the
      contralateral leg.
AB  - OBJECT: Evidence-based reviews support the use of venous thromboembolism (VTE)
      prophylaxis in the form of compression devices and/or stockings for patients
      undergoing craniotomy. In patients undergoing craniotomy with motor mapping for
      glioma, the contralateral lower extremity should remain visible so that motor
      responses can be accurately identified. As a consequence, these patients could be
      placed at a higher risk to develop VTE. The authors have quantified the incidence
      of VTE in patients undergoing craniotomy with motor mapping and have shown that
      there is no increased risk of developing a VTE in the contralateral lower
      extremity when compression devices are not used. METHODS: One hundred eighty
      consecutive cases (1997-2000) of craniotomy with motor mapping for glioma were
      retrospectively reviewed to determine the incidence and location of VTEs during
      the early postoperative course. Intraoperative VTE prophylaxis in all patients
      consisted of ipsilateral (that is, ipsilateral to the hemisphere being mapped)
      lower-extremity mechanical prophylaxis (antiembolism stocking plus compression
      device). Postoperatively, all patients received bilateral mechanical prophylaxis.
      Patients were observed until discharge and received clinical follow up. Venous
      thromboembolism, classified as deep venous thrombosis (DVT) or pulmonary embolism
      (PE) occurring within 6 weeks postoperatively, was confirmed by Doppler
      ultrasonography, spiral computerized tomography scanning, or both. The average
      duration of postoperative hospitalization was 5 days (range 2-59 days). Six
      patients (3.3%) experienced VTE. Of those, in four (2.2%) the DVT was localized
      to the contralateral (three patients) or ipsilateral (one patient) lower
      extremity. Two other patients (1.1%) only had PE. There were no deaths from
      thromboembolic complications and no statistically significant predisposition to
      VTE in the contralateral lower extremity among patients not receiving
      intraoperative prophylaxis. CONCLUSIONS: The incidence of VTE in patients
      undergoing craniotomy with motor mapping is comparable to that in patients
      receiving bilateral lower-extremity mechanical VTE prophylaxis. The practice of
      leaving the contralateral lower extremity free from intraoperative prophylaxis
      does not appear to place patients at a higher risk for developing VTE. There
      appears to be no preferential distribution of VTE in contralateral lower
      extremities that do not receive immediate preoperative and intraoperative
      mechanical prophylaxis.

PMID- 14567604
TI  - Management of vestibular schwannoma by fractionated stereotactic radiotherapy and
      associated cerebrospinal fluid malabsorption.
AB  - OBJECT: The goal of this study was to investigate outcomes in patients with
      vestibular schwannoma (VS) who were treated with fractionated stereotactic
      radiotherapy (SRT). METHODS: One hundred one patients with VS were treated with
      fractionated SRT at a radiation level of 40 to 50 Gy administered in 20 to 25
      fractions over a 5- to 6-week period. The median tumor size in these patients was
      19 mm (range 3-40 mm), and 27 tumors were larger than 25 mm. Patients were
      consistently followed up using magnetic resonance imaging every 6 months for 5
      years in principle. The median follow-up period was 45 months. The actuarial 5
      year rate of tumor control (no growth > 2 mm and no requirement for salvage
      surgery) was 91.4% (95% confidence interval 85.2-97.6%). Three patients with
      progressive tumors underwent salvage tumor resection. The actuarial 5-year rate
      of useful hearing preservation (Gardner-Robertson Class I or II) was 71%. The
      observed complications of fractionated SRT included transient facial nerve palsy
      (4% of patients), trigeminal neuropathy (14% of patients), and balance
      disturbance (17% of patients). No new permanent facial weakness occurred after
      fractionated SRT. Eleven patients (11%) who had progressive communicating
      hydrocephalus (cerebrospinal fluid malabsorption) and no evidence of tumor growth
      after fractionated SRT required a shunt. The symptoms of this type of
      hydrocephalus were similar to those of normal-pressure hydrocephalus and occurred
      4 to 20 months (median 12 months) after fractionated SRT. The mean size (+/-
      standard deviation) of tumors causing symptomatic hydrocephalus (25.5 +/- 7.8 mm)
      was significantly larger than that of other tumors (18.2 +/- 8.7 mm) (p = 0.011).
      Only four of the 72 patients with tumors smaller than 25 mm in maximum diameter
      received a shunt. CONCLUSIONS: Fractionated SRT resulted in an excellent tumor
      control rate, even for relatively large tumors, and produced a high rate of
      hearing preservation that was comparable to the best results of single-fraction
      radiosurgery. The progression of communicating hydrocephalus should be monitored
      closely, particularly in patients harboring a large VS.

PMID- 14567605
TI  - Fusobacterial brain abscess: a review of five cases and an analysis of possible
      pathogenesis.
AB  - OBJECT: The cases of five patients with fusobacterial brain abscess are
      presented. The authors discuss their attempt to determine the pathogenesis.
      METHODS: The clinical and microbiological features of five cases of fusobacterial
      brain abscess are reviewed. Isolates of 2031 Fusobacterium spp. and other
      anaerobes collected (1989-2002) at our institution were analyzed and compared for
      incidences and isolation sources. The findings were correlated with extensive
      literature on the subject. The five patients were men between 45 and 74 years of
      age. All experienced an insidious onset of the disease and probable hematogenous
      seeding of the organism(s). One patient had a monomicrobic Fusobacterium
      necrophorum abscess, whereas the others had polymicrobic F. nucleatum abscesses.
      Despite surgery and a regimen of antibiotic medications and dexamethasone, three
      patients experienced a paradoxical deterioration 3 days postoperatively that
      necessitated reevacuation of the lesion. The evacuants observed at that time
      contained numerous leukocytes but no microorganisms, suggesting intensified
      inflammation as the likely cause of deterioration. This explanation is supported
      by literature that fusobacteria strongly activate neutrophils. An analysis of the
      2031 anaerobes from blood, wounds, and abscesses showed the considerable
      virulence of Fusobacterium spp., which were able to enter and/or sustain
      themselves in the blood circulation. This pattern was similar to that of
      Clostridium spp., but different from those of Peptostreptococcus spp.,
      Bacteroides spp., and Prevotella spp., which were less invasive but more
      abundant. CONCLUSIONS: Some fusobacterial brain abscesses may be associated with
      a paradoxical postoperative deterioration, which is probably due to intensified
      inflammation following treatment. The blood-borne dissemination and invasive
      behavior of fusobacteria likely initiate such a brain abscess, and further
      seeding of other synergic bacteria leads to a polymicrobic abscess.

PMID- 14567606
TI  - Long-term motor effect of unilateral pallidal stimulation in 26 patients with
      advanced Parkinson disease.
AB  - OBJECT: The aim of this study was to evaluate the long-term effects of unilateral
      pallidal stimulation on motor function in selected patients with advanced
      Parkinson disease (PD). METHODS: The authors enrolled 26 patients with idiopathic
      PD in whom there was an asymmetric distribution of symptoms and, despite optimal
      pharmocological treatment, severe response fluctuations and/or dyskinesias. After
      the patient had received a local anesthetic agent, a quadripolar electrode
      (Medtronic model 3387) was implanted at the side opposite the side affected or,
      if both sides were affected, the side contralateral to the more affected side. No
      serious complications occurred. After 3 months, the total Unified PD Rating Scale
      (UPDRS) Part III score decreased by 50.7% while patients were in the off
      medication state (from 26.5 +/- 9.2 to 13.1 +/- 6.1) and by 55.4% while they were
      in the on-medication state (from 10.6 +/- 6.3 to 4.7 +/- 4.4). Only during the on
      state was the contralateral effect clearly more pronounced. The UPDRS Part IVa
      score decreased by 75% (from 3.7 +/- 2.5 to 0.9 +/- 1.1) and the UPDRS Part IVb
      score by 54.7% (from 3.3 +/- 1.3 to 1.5 +/- 1.3). At long-term follow-up review
      (32.7 +/- 10.7 months), there was an 8.3% increase in the UPDRS Part III score
      while patients were in the off state (from 26.5 +/- 9.2 to 28.7 +/- 7.6) and a
      40.2% increase in this score while patients were in the on state (from 10.6 +/-
      6.3 to 14.9 +/- 5.1). The UPDRS Part IVa score decreased by 28.1% (from 3.7 +/-
      2.5 to 2.7 +/- 2.3) and the UPDRS Part IVb score increased by 3.5% (from 3.3 +/-
      1.3 to 3.4 +/- 1.6). CONCLUSIONS: Based on these unsatisfactory results at long
      term review, the authors conclude that unilateral pallidal stimulation is not an
      effective treatment option for patients with advanced PD.

PMID- 14567607
TI  - Electrical stimulation of the posterior subthalamic area for the treatment of
      intractable proximal tremor.
AB  - OBJECT: Tremors, including its proximal component, are often refractory to
      standard thalamic surgery. In the 1960s the posterior part of the subthalamic
      white matter was reported to be a promising target in treating various forms of
      tremor, but was also found to be associated with adverse effects. Advances
      involving a less invasive method, that is, deep brain stimulation (DBS), has led
      to a reappraisal of this target. METHODS: Eight patients with severe essential
      tremor involving the proximal arm were treated using unilateral stimulation of
      the posterior part of the subthalamic white matter. The tentative target was
      situated in the area lateral to the red nucleus and posteromedial to the
      subthalamic nucleus. Macrostimulation was used to find the optimal site to
      suppress tremor. Through a quadripolar DBS lead, somatosensory evoked potentials
      (SSEPs) were recorded. Improvement of tremor was evaluated based on a modified
      clinical tremor rating scale. Anatomical locations of all contacts were assessed
      using stereotactic guidance and represented on the Schaltenbrand-Wahren atlas.
      CONCLUSIONS: A characteristic diphasic pattern of SSEPs reaffirmed the
      electrophysiological endorsement of this target. Tremors, both proximal and
      distal, were remarkably improved in all patients. The rate of improvement, as
      indicated by the total tremor score, was a mean of 81%. Axial tremors in the legs
      and head were also improved. Most of the contacts associated with remarkable
      improvement were located in the posterior part of the subthalamic white matter
      (the zona incerta and prelemniscal radiation). Neither major complications nor
      neurological deterioration was observed. The authors concluded that DBS of the
      posterior part of the subthalamic white matter together with SSEP recording is a
      safe and effective method to ameliorate severe intractable tremors.

PMID- 14567608
TI  - Writing, calculating, and finger recognition in the region of the angular gyrus:
      a cortical stimulation study of Gerstmann syndrome.
AB  - OBJECT: In an attempt to gain a better understanding of the cerebral functions
      represented in the angular gyrus and to spare them during surgery, the authors
      studied patients with brain tumors located close to the angular gyrus and mapped
      cortical sites by using electrostimulation. METHODS: Before undergoing tumor
      removal, six right-handed patients (five with left and one with right hemisphere
      tumors) were studied using cortical mapping with the aid of calculating, writing,
      finger-recognition, and color-naming tasks in addition to standard reading and
      object-naming tasks (for a total of 36 brain mapping studies). Strict conditions
      of functional site validation were applied to include only those cortical sites
      that produced repetitive interferences in the function tested. Preoperatively,
      four of the patients exhibited discrete symptoms related to Gerstmann syndrome
      while performing very specific tasks, whereas the other two patients presented
      with no symptoms of the syndrome. No patient had significant language or apraxic
      deficits. Distinct or shared cortical sites producing interferences in
      calculating, finger recognition, and writing were repeatedly found in the angular
      gyrus. Object- or color-naming sites and reading-interference sites were also
      found in or close to the angular gyrus; although frequently demonstrated, these
      latter results were variable and unpredictable in the group of patients studied.
      Finger agnosia and acalculia sites were also found elsewhere, such as in the
      supramarginal gyrus or close to the intraparietal sulcus. Mechanisms involved in
      acalculia, agraphia, or finger agnosia (either complete interferences or
      hesitations) during stimulation were various, from an aphasia-like form (for
      instance, the patient did not understand the numbers or words given for
      calculating or writing tasks) to an apparently pure interference in the function
      tested (patients understood the numbers, but were unable to perform a simple
      addition). CONCLUSIONS: Symptoms of Gerstmann syndrome can be found during direct
      brain mapping in the angular gyrus region. In this series of patients, sites
      producing interferences in writing, calculating, and finger recognition were
      demonstrated in the angular gyrus, which may or may not have been associated with
      object-naming, color-naming, or reading sites.

PMID- 14567610
TI  - Transcriptional expression of survivin and its splice variants in brain tumors in
      humans.
AB  - OBJECT: Survivin, one of the apoptosis inhibitor proteins, has been detected in
      most cancers in humans. In addition, two splice variants (survivin-2B and
      survivin-deltaEx3) have been identified. The authors investigated the
      transcription levels of survivin messenger (m)RNA and its splice variants in nine
      tumor cell lines, including gliomas, and in 25 brain tumor samples, by performing
      quantitative reverse transcription-polymerase chain reaction. The correlation
      between transcript expression levels and pathological findings were also
      analyzed. METHODS: Transcription levels were measured using primer pairs specific
      for survivin and either of its splice variants and were normalized to the
      glyceraldehyde 6-phosphate dehydrogenase. Among the tumor cell lines tested,
      glioblastoma cell lines showed the highest levels of survivin expression. Among
      brain tumor samples studied, survivin was preferentially expressed in malignant
      brain tumors and gliomas. The relative expression level of survivin
      deltaEx3/survivin was significantly higher in malignant than in benign brain
      tumor samples. Expression patterns were dominant for survivin-deltaEx3 in
      malignant brain tumors and dominant for survivin-2B in benign ones. A significant
      linear correlation between survivin mRNA expression and MIB-1 labeling index was
      demonstrated in all brain tumor samples. CONCLUSIONS: The authors' results
      indicate that quantifying the levels of survivin and its splice variants is
      useful for the prediction of the cell biological malignancy of gliomas,
      independent of their pathological features.

PMID- 14567609
TI  - Selective opening of the blood-tumor barrier by a nitric oxide donor and long
      term survival in rats with C6 gliomas.
AB  - OBJECT: The response of brain tumors to systemic chemotherapy is limited by the
      blood-tumor barrier (BTB). Nitric oxide (NO) has been implicated in the
      regulation of vascular permeability and blood flow. The authors evaluated the
      effects of exogenous NO, which was released from a short-acting NO donor
      (Proli/NO), and those of NO metabolites on the capillary permeability of tumors
      and normal brain tissue by using quantitative autoradiography in a C6 glioma
      model in rats. METHODS: The Proli/NO was infused at a wide dose range (10(-2) to
      10(-12) M) either intravenously or into the internal carotid artery (ICA) and
      demonstrated substantial tumor-selective increases in blood-brain barrier (BBB)
      permeability in response to various-sized tracers ([14C]aminoisobutyric acid,
      [14C]sucrose, [14C]dextran). Internal carotid artery or intravenous
      administration of sodium nitrite had a comparable effect on BTB permeability. The
      NO effect on microvascular permeability could be obtained without causing
      hemodynamic side effects. The effect of NO on the efficacy of carboplatin
      chemotherapy was investigated in intracerebral C6 gliomas. Simultaneous
      intravenous infusions of Proli/NO (10(-6) M) and carboplatin (20 mg/kg) led to
      long-term survival in 40% of rats harboring intracerebral C6 gliomas compared
      with control animals receiving ICA or intravenous infusions of carboplatin,
      Proli/NO, or vehicle alone. No residual tumor was demonstrated on histological or
      magnetic resonance imaging studies performed in rats treated with Proli/NO and
      carboplatin, and no toxicity was observed. CONCLUSIONS: This new approach
      demonstrated the in vivo efficacy and safety of NO and nitrite in enhancing the
      delivery of systemically delivered radiolabeled tracers and carboplatin into rat
      gliomas. The NO-induced tumor-selective BBB disruption and intravenous
      carboplatin chemotherapy may be more efficacious than current chemotherapy
      strategies against brain tumors.

PMID- 14567611
TI  - Induction of an antitumor immunological response by an intratumoral injection of
      dendritic cells pulsed with genetically engineered Semliki Forest virus to
      produce interleukin-18 combined with the systemic administration of interleukin
      12.
AB  - OBJECT: The aim of this study was to investigate further immunogene treatment of
      malignant brain tumor to improve its therapeutic efficacy. METHODS: Intratumoral
      dendritic cells pulsed with Semliki Forest virus (SFV)-interleukin-18 (IL-18)
      and/or systemic IL-12 were injected into mice bearing the B16 brain tumor. To
      study the immune mechanisms involved in tumor regression, we monitored the growth
      of implanted B16 brain tumor cells in T cell-depleted mice and IFNgamma
      neutralized mice. To analyze the protective immunity created by tumor
      inoculation, B16 cells were injected into the left thighs of mice that had
      received an inoculation, and tumor growth was monitored. The local delivery of
      dendritic cells pulsed with IL-18 bound by SFV combined with the systemic
      administration of IL-12 enhanced the induction of the T helper type 1 response
      from tumor-specific CD4+ and CD8+ T cells and natural killer cells as well as
      antitumor immunity. Interferon-gamma is partly responsible for this IL-18
      mediated antitumor immunity. Furthermore, the protective immunity is mediated
      mainly by CD8+ T cells. CONCLUSIONS: Immunogene therapy that combines the local
      administration of dendritic cells pulsed with IL-18 bound by SFV and the systemic
      administration of IL-12 may be an excellent candidate for the development of a
      new treatment protocol. A self-replicating SFV system may therefore open a novel
      approach for the treatment of malignant brain tumor.

PMID- 14567613
TI  - Effect of ipsilateral subthalamic nucleus lesioning in a rat parkinsonian model:
      study of behavior correlated with neuronal activity in the pedunculopontine
      nucleus.
AB  - OBJECT: The purpose of this study was to investigate the spontaneous behavioral
      changes and the alteration of neuronal activities in the pedunculopontine nucleus
      (PPN) after ipsilateral subthalamic nucleus (STN) lesioning by kainic acid in a
      rat parkinsonian model created by lesioning with 6-hydroxydopamine (6-OHDA).
      METHODS: Assumptions about the mechanisms mediating the effects of lesioning of
      the nigrostriatal dopaminergic pathway by 6-OHDA and the effects of STN lesioning
      were examined behaviorally by means of apomorphine-induced rotational behavior
      and forepaw-adjusting steps. The authors subsequently investigated the alteration
      of neuronal activities in the PPN to compare them with the behavioral changes in
      rat parkinsonian models. CONCLUSIONS: The results demonstrated that STN lesioning
      induced behavioral improvement in rat parkinsonian models. This result, which
      confirms previously held assumptions, may account for the therapeutic effect of
      STN stimulation in Parkinson disease. The alteration of the neuronal activities
      in the PPN units also indicates that the PPN units are responsible for the
      improvement in motor symptoms observed after STN lesioning in rat parkinsonian
      models.

PMID- 14567612
TI  - Sympathetic mechanisms in cerebral blood flow alterations induced by spinal cord
      stimulation.
AB  - OBJECT: Cervical spinal cord stimulation (SCS) has been found to augment cerebral
      blood flow (CBF) in a number of animal models, although the mechanisms underlying
      the cerebrovascular effects of SCS are poorly described. In this study, the
      authors examined the role of sympathetic tone in CBF alterations induced by SCS
      in rats. METHODS: Spinal cord stimulation was performed at three intervals while
      CBF was monitored with laser Doppler flowmetry (LDF). Either hexamethonium (5,
      10, or 20 mg/kg), prazosin (0.25, 0.5, or 1 mg/kg), idazoxan (0.5, 1, or 2
      mg/kg), propranolol (1, 2, or 4 mg/kg), or vehicle was administered intravenously
      before the second stimulation. Changes in LDF values due to SCS were recorded as
      the percentage of change from baseline values and were analyzed. In vehicle
      treated animals, SCS increased LDF values by 60.5 +/- 1.8% over baseline, whereas
      both high-dose hexamethonium and prazosin completely abolished the SCS-induced
      increases in LDF values. On the other hand, LDF values increased by 50.9 +/- 4%
      and 61.4 +/- 4% after SCS in the presence of idazoxan or propranolol,
      respectively. Administration of sympathetic nervous system blockers resulted in a
      variable degree of systemic hypotension as well. Nevertheless, induced
      hypotension without sympathetic blockade had only a minimal effect on SCS-induced
      augmentation of LDF values (48 +/- 1.4% over baseline). CONCLUSIONS: Sympathetic
      tone plays a major role in SCS-induced increases in CBF. This effect seems to be
      mediated primarily by alpha1-adrenergic receptors. Systemic hypotension alone
      cannot explain the effects of sympathetic blockade on the SCS response. Clinical
      use of SCS in the treatment of cerebral ischemia should take alpha1-adrenergic
      receptor sympathetic tone into account.

PMID- 14567614
TI  - Attenuation of cerebellar tremor with implantation of an intrathecal baclofen
      pump: the role of gamma-aminobutyric acidergic pathways. Case report.
AB  - The authors present the case of a 49-year-old woman with disabling bilateral
      upper-extremity cerebellar tremor that resolved unexpectedly after placement of
      an intrathecal baclofen pump for lower-extremity spasticity. The tremor amplitude
      decreased nearly linearly with increasing intrathecal baclofen dosage, and
      disappeared completely at a dose of 250 microg/day. In this report the authors
      demonstrate the role of the gamma-aminobutyric acidergic system in the
      pathogenesis of cerebellar tremor, and these findings may lead to a new treatment
      modality for patients disabled by this manifestation of their disease.

PMID- 14567615
TI  - Transient dystonia following magnetic resonance imaging in a patient with deep
      brain stimulation electrodes for the treatment of Parkinson disease. Case report.
AB  - Data from previous studies have shown that magnetic resonance (MR) imaging of the
      head can be performed safely in patients with deep brain stimulators. The authors
      report on a 73-year-old patient with bilaterally implanted deep brain electrodes
      for the treatment of Parkinson disease, who exhibited dystonic and partially
      ballistic movements of the left leg immediately after an MR imaging session. Such
      dystonic or ballistic movements had not been previously observed in this patient.
      In the following months, this focal movement disorder resolved completely. This
      case demonstrates the possible risks of MR imaging in patients with deep brain
      stimulators.

PMID- 14567616
TI  - Transarterial approach for selective intravenous coil embolization of a benign
      dural arteriovenous fistula. Case report.
AB  - Transarterial particulate embolization is indicated for benign intracranial dural
      arteriovenous fistulas (DAVFs) that have no dangerous venous reflux. This
      treatment, however, does not cure these lesions. In this case report the authors
      describe a spontaneously occurring DAVF that was treated by implanting coils
      through a transarterial microcatheter into the affected venous channel. The
      channel was separate from the normal dural sinuses. The pathological architecture
      of the fistula and the usefulness of this approach are discussed.

PMID- 14567617
TI  - Evolution of a cochlear schwannoma on clinical and neuroimaging studies. Case
      report.
AB  - The authors report on a patient with a rare schwannoma that arose from the
      cochlear division of the vestibulocochlear nerve. Distinctively, the lesion
      appeared to arise from the cochlea itself and was monitored with clinical and
      neuroimaging studies for 12 years before it was diagnosed and treated. The
      atypical occurrence of schwannomas of the vestibulocochlear nerve originating in
      the inner ear structures underscores the high level of clinical suspicion
      required for the diagnosis of these lesions in patients presenting with
      persistent auditory and vestibular symptoms.

PMID- 14567618
TI  - Dual-floor burr hole adjusted to burr-hole ring and cap for implantation of
      stimulation electrodes. Technical note.
AB  - Using a new perforator, the authors have developed a new dual-floor burr-hole
      method for use in deep brain stimulation therapy. The modification is called
      "dual-floor" because the usual 15-mm-diameter burr hole, which is located
      centrally and reaches the dura mater, is surrounded by a 4-mm-wide rim that is
      also planed downward by the new perforator to a depth of 4 mm. This dual-floor
      burr hole is adjusted to fit the burr-hole ring and cap that are are supplied by
      the electrode manufacturer. Such a method eliminates bulging of the scalp just
      over the burr-hole ring and cap. In addition, it is helpful for securing a tight
      fixation between the burr-hole ring and the skull.

PMID- 14567619
TI  - Percutaneous trigeminal nerve radiofrequency rhizotomy guided by computerized
      tomography fluoroscopy. Technical note.
AB  - The authors describe a new procedure for percutaneous trigeminal radiofrequency
      rhizotomy. Computerized tomography fluoroscopy is used for guidance of the
      rhizotomy needle insertion through the foramen ovale. Ten patients were treated
      using this method, and in each case the target was reached with a single
      puncture. The potential benefits of this method are presented.

PMID- 14567620
TI  - Harvey Cushing's Meningiomas text and the historical origin of resectability
      criteria for the anterior one third of the superior sagittal sinus.
AB  - The search for the origin of the commonly held principle in current neurosurgery
      regarding the resectability of the anterior one third of the superior sagittal
      sinus unravels the many fascinating developments that occurred in neurosurgery
      during the early 20th century. All these occurrences can be traced back to, and
      are uniquely contextualized in, Harvey Cushing's seminal text, Meningiomas, Their
      Classification, Regional Behaviour, Life History, and Surgical End Results.
      Written with Louise Eisenhardt and published in 1938, Meningiomas is a monograph
      of incredible description and detail. The meticulous categorization of
      meningiomas, their presentation, clinical outcome, and surgical therapies are
      even further supplemented by Cushing's personal commentary, questions, and
      recollections. Cushing's genius was evident in his ability not only to make
      insightful clinical observations, but also to synthesize these ideas within the
      neurosurgical context of his era. As he says in Meningiomas, "Thus the
      pathological curiosity of one day becomes in its proper time a commonplace...
      most of which are one and the same disorder--had, for their interpretation, to
      await the advent of the Neurosurgeon."

PMID- 14567621
TI  - Pontine hemorrhage.

PMID- 14567622
TI  - Normal-pressure hydrocephalus and Alzheimer disease.

PMID- 14567623
TI  - Hyperventilation.

PMID- 14567624
TI  - Otorrhea.

PMID- 14567625
TI  - Physical stability of proteins in aqueous solution: mechanism and driving forces
      in nonnative protein aggregation.
AB  - Irreversible protein aggregation is problematic in the biotechnology industry,
      where aggregation is encountered throughout the lifetime of a therapeutic
      protein, including during refolding, purification, sterilization, shipping, and
      storage processes. The purpose of the current review is to provide a fundamental
      understanding of the mechanisms by which proteins aggregate and by which varying
      solution conditions, such as temperature, pH, salt type, salt concentration,
      cosolutes, preservatives, and surfactants, affect this process.

PMID- 14567627
TI  - Involvement of Nrf2 and JNK1 in the activation of antioxidant responsive element
      (ARE) by chemopreventive agent phenethyl isothiocyanate (PEITC).
AB  - PURPOSE: Phenethyl isothiocyanate (PEITC) has been of great interest as a
      promising cancer chemopreventive agent. To better understand its chemopreventive
      activity, we examined the effect of PEITC on the antioxidant responsive element
      (ARE), which is an important gene regulatory element of many phase II drug
      metabolizing/detoxification enzymes as well as cellular defensive enzymes.
      METHODS: HeLa cells were transiently transfected with different cDNA plasmids
      using calcium phosphate precipitation. Subsequently, the cells were maintained in
      fresh media, and various concentrations of PEITC were added to the transfected
      cells. After harvesting and lysing of the cells, ARE-luciferase reporter gene
      activity was measured and normalized against beta-galactosidase activity.
      RESULTS: Treatments of HeLa cells with PEITC transiently stimulated ARE-reporter
      gene expressions in a dose-dependent manner. Overexpression of wild-type NF-E2
      related factor-2 (Nrf2) dramatically increased ARE-reporter gene expression in a
      dose-dependent manner. Similar effects were seen when wild-type c-Jun N-terminal
      kinase 1 (JNK1) was transfected, although the transactivating potential of JNK1
      was much less than that of Nrf2. Cotransfection of Nrf2 and JNK1 showed
      additional enhancement of ARE reporter gene expression, implying that JNK1 might
      be an upstream activator of Nrf2. To support this, overexpression of dominant
      negative JNK1 suppressed Nrf2-induced ARE reporter gene expression in a dose
      dependent manner. When PEITC was added, slight enhancement of ARE reporter gene
      expression was observed in either Nrf2- or JNK1-transfected cells. Finally, ARE
      reporter activity induced by PEITC was substantially attenuated by transfection
      of either dominant-negative mutant of Nrf2 or dominant-negative mutant of JNK1.
      CONCLUSION: Taken together, these data suggest that JNK1 acts as an upstream
      activator of Nrf2 and that PEITC activates ARE-mediated phase II drug metabolism
      gene expressions via the JNK1- and Nrf2-dependent pathways.

PMID- 14567626
TI  - Drug delivery and transport to solid tumors.
AB  - PURPOSE: The purpose of this review is to provide an overview of the principles
      of and barriers to drug transport and delivery to solid tumors. METHODS: This
      review consists of four parts. Part I provides an overview of the differences in
      the vasculature in normal and tumor tissues, and the relationship between tumor
      vasculature and drug transport. Part II describes the determinants of transport
      of drugs and particles across tumor vasculature into surrounding tumor tissues.
      Part III discusses the determinants and barriers of drug transport, accumulation,
      and retention in tumors. Part IV summarizes the experimental approaches used to
      enhance drug delivery and transport in solid tumors. RESULTS: Drug delivery to
      solid tumors consists of multiple processes, including transport via blood
      vessels, transvascular transport, and transport through interstitial spaces.
      These processes are dynamic and change with time and tumor properties and are
      affected by multiple physicochemical factors of a drug, multiple tumor biologic
      factors, and as a consequence of drug treatments. The biologic factors, in turn,
      have opposing effects on one or more processes in the delivery of drugs to solid
      tumors. CONCLUSION: The effectiveness of cancer therapy depends in part on
      adequate delivery of the therapeutic agents to tumor cells. A better
      understanding of the processes and contribution of these factors governing drug
      delivery may lead to new cancer therapeutic strategies.

PMID- 14567628
TI  - Evaluation of an immortalized retinal endothelial cell line as an in vitro model
      for drug transport studies across the blood-retinal barrier.
AB  - PURPOSE: To evaluate the growth and barrier properties of an immortalized rat
      retinal endothelial cell line (TR-iBRB) maintained on permeable membrane for drug
      transport studies. METHODS: TR-iBRB cells were grown on permeable membrane
      filters. The effect of coating material on cell growth was investigated.
      Transport of [14C]-3-O-methyl-D-glucose (3-OMG), AGN 194716, AGN 195127, AGN
      197075, acebutolol, alprenolol, atenolol, brimonidine, carbamazepine epoxide (CBZ
      E), metoprolol, nadolol, rhodamine 123, and sotalol was measured across the
      cultured cell layer to determine the apparent permeability coefficients (Papp).
      Rhodamine 123 uptake into these cells in the presence of these test compounds was
      evaluated. Western blot was performed to detect the efflux transporter P
      glycoprotein (P-gp). Bidirectional transport in MDR1-MDCK cell monolayers
      overexpressing the human P-gp was measured for AGN 197075. RESULTS: TR-iBRB cells
      form confluent cell layers when grown on fibronectin-coated membrane and exhibit
      characteristic spindle-shaped morphology. A good correlation between Papp and
      cLogD (pH 7.4) of the compounds tested was observed, except for 3-OMG, AGN
      197075, and rhodamine 123, which are substrates of carrier-mediated transport
      systems such as P-gp and a glucose transporter (GLUT1). When grown on permeable
      membrane, TR-iBRB cells expressed functional P-gp and GLUT1. CONCLUSIONS: TR-iBRB
      cells, when grown on permeable membrane, provide a useful tool for predicting
      permeability across the BRB. The usefulness of this model for high-throughput
      screening and rank ordering of drug candidates intended for the back of the eye
      in treatment of ocular diseases needs further characterization upon correlation
      with in vivo data.

PMID- 14567629
TI  - Preliminary investigation into the expression of proton-coupled oligopeptide
      transporters in neural retina and retinal pigment epithelium (RPE): lack of
      functional activity in RPE plasma membranes.
AB  - PURPOSE: To determine the expression and functional activity of proton-coupled
      oligopeptide transporters (POT) in retinal pigment epithelial (RPE) cells.
      METHODS: RT-PCR was used to probe the presence of POT mRNA in freshly isolated
      bovine RPE (BRPE) and human RPE (HRPE) cells, a human RPE cell line (ARPE-19),
      and human and bovine neural retina. [14C]GlySar uptake was used to characterize
      POT activity in cultured ARPE-19 cells and freshly isolated BRPE cell sheet
      suspensions. RESULTS: PHT1 mRNA was expressed in BRPE, HRPE, ARPE-19, and bovine
      and human neural retina. In contrast, PEPT2 and PHT2 were expressed only in
      bovine and human retina, and PEPT1 could not be detected. GlySar exhibited a
      linear uptake over 6 h at pH values of 6.0 and 7.4, with greater uptake at pH 7.4
      (p < 0.01). GlySar uptake did not exhibit saturability (5-2000 microM) and was
      unchanged when studied in the presence of 1 mM L-histidine. In contrast, GlySar
      uptake was significantly decreased when studied at 4 degrees C or in the presence
      of endocytic inhibitors at 37 degrees C (p < 0.01). Studies in BRPE cell sheet
      suspensions validated the results obtained in ARPE-19 cells and strongly
      suggested the absence of POT on the apical and basolateral membranes of RPE.
      CONCLUSIONS: PHT1 mRNA is present in native bovine and human RPE and a human RPE
      cell line. However, the data argue against PHT1 being expressed on plasma
      membranes of RPE. Overall, GlySar appears to be taken up by RPE cells via a low
      affinity, endocytic process.

PMID- 14567630
TI  - Assessment of temporal biochemical and gene transcription changes in rat liver
      cytochrome P450: utility of real-time quantitative RT-PCR.
AB  - PURPOSE: A conventional approach to assess cytochrome P450 (CYP) induction in
      preclinical animal models involves daily dosing for a least a week followed by
      Western blot and/or enzyme activity analysis. To evaluate the potential benefit
      of a third more specific and sensitive assay, real-time quantitative reverse
      transcription polymerase chain reaction (qRT-PCR), with the objective of reducing
      the duration of the conventional 1-week study, we simultaneously assessed gene
      expression by qRT-PCR along with Western blots and enzyme activity assays as a
      time course in an in vivo model. METHODS: Rats were dosed daily for 8 days with
      model inducers of CYP1A, CYP2B, CYP3A, or CYP4A. Liver P450 levels were measured
      after 0.5, 1, 2, 4, and 8 days of dosing by qRT-PCR, Western blot, and enzyme
      activity. RESULTS: CYP1A, CYP3A, and CYP4A genes were maximally induced very
      rapidly (0.5-1 day), whereas the CYP2B gene was maximally induced after a lag
      time of 4 days. In all cases, fold changes in induction detected by qRT-PCR were
      greater than fold changes in protein levels and enzyme activities. CONCLUSIONS:
      Maximal persistent and larger fold changes observed by qRT-PCR either preceded or
      occurred simultaneously with maximal sustained fold changes in protein levels as
      measured by Western blots and enzyme activity assays. Our data show that qRT-PCR
      provides increased sensitivity and specificity over conventional assays and may
      be key information for reliable assessment of drug-related changes in CYP
      induction during the transition from discovery to toxicology studies.

PMID- 14567631
TI  - Amino acid ester prodrugs of floxuridine: synthesis and effects of structure,
      stereochemistry, and site of esterification on the rate of hydrolysis.
AB  - PURPOSE: To synthesize amino acid ester prodrugs of floxuridine (FUdR) and to
      investigate the effects of structure, stereochemistry, and site of esterification
      of promoiety on the rates of hydrolysis of these prodrugs in Caco-2 cell
      homogenates. METHODS: Amino acid ester prodrugs of FUdR were synthesized using
      established procedures. The kinetics of hydrolysis of prodrugs was evaluated in
      human adenocarcinoma cell line (Caco-2) homogenates and pH 7.4 phosphate buffer.
      RESULTS: 3'-Monoester, 5'-monoester, and 3',5'-diester prodrugs of FUdR utilizing
      proline, L-valine, D-valine, L-phenylalanine, and D-phenylalanine as promoieties
      were synthesized and characterized. In Caco-2 cell homogenates, the L-amino acid
      ester prodrugs hydrolyzed 10 to 75 times faster than the corresponding D-amino
      acid ester prodrugs. Pro and Phe ester prodrugs hydrolyzed much faster (3- to 30
      fold) than the corresponding Val ester prodrugs. Further, the 5'-monoester
      prodrugs hydrolyzed significantly faster (3-fold) than the 3',5'-diester
      prodrugs. CONCLUSIONS: Novel amino acid ester prodrugs of FUdR were successfully
      synthesized. The results presented here clearly demonstrate that the rate of FUdR
      prodrug activation in Caco-2 cell homogenates is affected by the structure,
      stereochemistry, and site of esterification of the promoiety. Finally, the 5'-Val
      and 5'-Phe monoesters exhibited desirable characteristics such as good solution
      stability and relatively fast enzymatic conversion rates.

PMID- 14567632
TI  - Inhibitory effect of zinc on PEPT1-mediated transport of glycylsarcosine and beta
      lactam antibiotics in human intestinal cell line Caco-2.
AB  - PURPOSE: The aim of this study was to examine the effects of zinc on the
      intestinal peptide transporters (PEPT1 and basolateral peptide transporter) and
      to elucidate the mechanism of the interactions. METHODS: Caco-2 cells were
      pretreated with zinc, and the uptake studies were carried out. RESULTS: Zinc
      treatment resulted in the inhibition of [14C]glycylsarcosine (Gly-Sar) uptake via
      PEPT1 in a concentration-dependent manner, whereas it showed moderate inhibitory
      effect on the basolateral peptide transporter. Zinc also inhibited the uptake of
      oral beta-lactam antibiotics such as ceftibuten and cephradine by PEPT1. Kinetic
      analysis showed that zinc treatment increased Km values without affecting Vmax
      values of the [14C]Gly-Sar uptake. The inhibition of [14C]Gly-Sar uptake induced
      by zinc was observed in the presence of an H+ gradient but not in the absence of
      an H+ gradient. CONCLUSIONS: These results indicate that zinc is a competitive
      inhibitor of PEPT1. Zinc inhibited the PEPT1 function, possibly by interacting
      with histidine residues of PEPT1 that are part of an H+-binding site. These
      findings would provide important information for clinical, physiologic, and
      biochemical aspects of peptide transporters.

PMID- 14567633
TI  - Involvement of multidrug resistance associated protein 1 (Mrp1) in the efflux
      transport of 17beta estradiol-D-17beta-glucuronide (E217betaG) across the blood
      brain barrier.
AB  - PURPOSE: The purpose of present study is to investigate the involve ment of
      multidrug resistance-associated protein 1 (Mrp1), Mrp2, an P-glycoprotein (Mdr1a)
      in the efflux transport of 17beta-estradiol-D-17beta-glucuronide (E217betaG)
      across the blood-brain barrier (BBB). METHOD: The expression of Mrp1 and Mrp2 at
      the BBB was investigated by RT-PCR and Western blot analyses. The time profiles
      of the remaining radioactivity of [3H]E217pG in the brain were compared in wild
      type, Mdr1a/Mdr1b and Mrp1 knockout mice and normal and Mrp2-deficient mutant
      rats [Sprague-Dawley and Eisai hyperbilirubinemic rats (EHBR), respectively]
      after intracerebral microinjection. RESULTS: RT-PCR and Western blot analyses
      revealed the expression of Mrp1 in isolated rat brain capillary; however, RT-PCR
      was unable to detect any expression of Mrp2. Significant elimination of E217betaG
      was observed in wild-type mice at a rate constant of 0.007 min(-1) which was
      significantly decreased (0.004 min(-1)) in Mrp1 knockout mice. In contrast, there
      was no difference in the efflux of E217betaG from the brain in wild-type and
      Mdr1a/Mdr1b knockout mice and in normal and EHBR. No significant difference was
      observed in the accumulation of E217betaG by brain slices prepared from wild-type
      and Mrp1 knockout mice. CONCLUSION: Mrp1, but not Mrp2, is involved in the
      excretion of E217betaG at the BBB and provides a barrier function by extruding
      conjugated metabolites into the blood.

PMID- 14567634
TI  - QSAR analysis of the inhibition of recombinant CYP 3A4 activity by structurally
      diverse compounds using a genetic algorithm-combined partial least squares
      method.
AB  - PURPOSE: To develop a quantitative structure/activity relationship (QSAR) model
      for predicting drug-CYP 3A4 interactions. METHOD: The inhibitory effect of 53
      structurally diverse drugs on the metabolism of 7-benzyloxy-4-trifluoromethyl
      coumarin (BFC) by recombinant CYP 3A4 was evaluated using a rapid microtiter
      plate assay. For each drug, a total of 220 two-dimensional topological indices
      were calculated using Molconn-Z software. Using a genetic algorithm-based partial
      least squares (GA-PLS) method, the desired descriptors were automatically
      selected to maximize the predictability of the IC50 values. RESULTS: The IC50
      values of the drugs tested ranged from 9 nM to 2 mM. Based on the GA-PLS method,
      five principal components derived from 20 Molconn-Z descriptors were found to be
      effective for QSAR modeling. Interestingly, these descriptors suggested that the
      molecular size would be an important factor in determining drug-CYP 3A4
      interactions. In the leave-one-out prediction, the rpred and the standard error
      of prediction (s) were 0.754 and 0.787, respectively. Even in an external
      validation, the predictions were in good agreement with experimental values
      (rpred = 0.744, s = 0.769, n = 9). CONCLUSIONS: The proposed model, in which two
      dimensional topological descriptors were used as molecular descriptors, was able
      to predict drug-CYP 3A4 interactions with reasonable accuracy.

PMID- 14567635
TI  - Ocular pharmacokinetic modeling using corneal absorption and desorption rates
      from in vitro permeation experiments with cultured corneal epithelial cells.
AB  - PURPOSE: To determine corneal absorption and desorption rate constants in a
      corneal epithelial cell culture model and to apply them to predict ocular
      pharmacokinetics after topical ocular drug application. METHOD: In vitro
      permeation experiments were performed with a mixture of six beta-blockers using
      an immortalized human corneal epithelial cell culture model. Disappearance of the
      compounds from the apical donor solution and their appearance in the basolateral
      receiver solution were determined and used to calculate the corneal absorption
      and desorption rate constants. An ocular pharmacokinetic simulation model was
      constructed for timolol with the Stella program using the absorption and
      desorption rate constants and previously published in vivo pharmacokinetic
      parameters. RESULTS: The corneal absorption rates of beta-blockers increased
      significantly with the lipophilicity of the compounds. The pharmacokinetic
      simulation model gave a realistic mean residence time for timolol in the cornea
      (57 min) and the aqueous humor (90 min). The simulated timolol concentration in
      the aqueous humor was about 1.8 times higher than the previously published
      experimental values. CONCLUSIONS: The simulation model gave a reasonable estimate
      of the aqueous humor concentration profile of timolol. This was the first attempt
      to combine cell culture methods and pharmacokinetic modeling for prediction of
      ocular pharmacokinetics. The wider applicability of this approach remains to be
      seen.

PMID- 14567636
TI  - The effect of low concentrations of molecularly dispersed poly(vinylpyrrolidone)
      on indomethacin crystallization from the amorphous state.
AB  - PURPOSE: To investigate the effect of low concentrations of molecularly dispersed
      poly(vinylpyrrolidone) (PVP) on indomethacin (IMC) crystallization from the
      amorphous state using particle size effects to identify possible mechanisms of
      crystallization inhibition. METHODS: Different particle sizes of amorphous IMC
      and 1, 2, and 5% PVP were stored dry at 30 degrees C for 84 days. PXRD was used
      to calculate the rate and extent of crystallization and the polymorph formed.
      RESULTS: Crystallization from amorphous IMC and IMC/PVP molecular dispersions
      yielded the gamma polymorph of IMC. Crystallization rates were reduced at larger
      particle size and in the presence of 1, 2, and 5%PVP. Crystallization did not
      reach completion in some IMC/PVP samples, with the quantity of uncrystallized
      amorphous phase proportional to particle size. CONCLUSIONS: Low concentrations of
      molecularly dispersed PVP affected IMC crystallization from the amorphous state.
      Formation of gamma-IMC at rates dependent on particle size indicated that surface
      nucleation predominated in both the absence and presence of PVP. Excellent
      correlation was seen between the extent of crystallization and simulated depths
      of crystal penetration, supporting the hypothesis that increasing local PVP
      concentration inhibits crystal growth from surface nuclei into the amorphous
      particle.

PMID- 14567637
TI  - Thermal analysis of trace levels of polymorphic impurity in salmeterol xinafoate
      samples.
AB  - PURPOSE: To quantify trace levels of polymorphic impurity in two salmeterol
      xinafoate (SX) Form I samples: granular SX (GSX) produced by fast-cooling
      crystallization and micronized SX (MSX) prepared from GSX by micronization.
      METHODS: SX-I and SX-II produced by solution enhanced dispersion by supercritical
      fluids (SEDS) were the reference polymorphs (100% pure) used for quantitative
      comparison. The percentage of polymorphic conversion, alpha, of each Form I
      sample to Form II was measured by differential scanning calorimetry (DSC) as a
      function of time (i.e., at different scanning speeds). The data were analyzed by
      the Avrami-Erofe'ev (AE) equation using an iterative fitting computer program. SX
      I samples containing 1.24, 4.41, and 13.47% (w/w) of SX-II as physical mixtures
      were subjected to similar analysis and data treatment. A mathematical
      relationship based on an instantaneous nucleation model was derived to relate the
      AE rate constants, k, of pure SX-I and physical mixtures to weight percentage of
      SX-II. This relationship was then used to calculate the percentage polymorphic
      impurity of GSX and MSX from their k values. For relative comparison of the Form
      II nuclei present, the k values of SX-I, GSX, and MSX were used to calculate
      their differences in free energy of nucleation. RESULTS: The AE equation affords
      good (r2 approximately equal to 0.81) to excellent (r2 approximately equal to
      0.99) fits of data for the samples. The levels of polymorphic impurity in GSX and
      MSX are 0.16 and 0.62% (w/w), respectively. Based on the free energy differences
      of nucleation between the reference SX-I material and the other samples, the
      number (and size) of the Form II nuclei present in the samples rank in the order:
      MSX > GSX > SX-I. CONCLUSIONS: DSC is a useful tool for assessing the polymorphic
      purity of SX materials and possibly other enantiotropic pairs showing similar
      thermal behavior.

PMID- 14567638
TI  - Direct observation of the enthalpy relaxation and the recovery processes of
      maltose-based amorphous formulation by isothermal microcalorimetry.
AB  - PURPOSE: The applicability of isothermal microcalorimetry (IMC) for evaluating
      enthalpy relaxation and recovery processes of amorphous material was assessed.
      METHODS: A maltose-based formulation was prepared by freeze-dry method.
      Differential scanning calorimetry (DSC) was used to investigate its glass
      transition and relaxation behaviors. IMC was applied to quantitatively analyze
      the relaxation and the recovery processes. The IMC data were analyzed using a
      derivative of the Kohlrausch-Williams-Watts equation. RESULTS: The glass
      transition temperature of the formulation and its fictive temperature stored at
      15 degrees C for 1 year were 62 and 32 degrees C, respectively. DSC study showed
      that annealing below the fictive temperature increased the enthalpy recovery, but
      it was decreased by annealing at higher temperatures. IMC enabled direct
      observation of the heat flow during both the relaxation and the recovery
      processes. The decay constant for the recovery process (recovery time) was much
      smaller and less sensitive to the temperature than that for the relaxation
      process (relaxation time). CONCLUSIONS: IMC was successfully used to obtain
      quantitative information on both relaxation and recovery processes of amorphous
      material. The relaxation parameters obtained by this method could explain the
      thermodynamic behavior of the formulation.

PMID- 14567640
TI  - PEGylated adenoviruses for gene delivery to the intestinal epithelium by the oral
      route.
AB  - PURPOSE: Adenoviruses are being developed for diseases of the gastrointestinal
      tract. Several in vitro assays were used to predict stability of PEGylated
      adenovirus along the GI tract and determine in vivo gene transfer after oral
      administration. METHODS: Recombinant adenovirus was modified with
      monomethoxypoly(ethylene) glycols activated by cyanuric chloride, succinimidyl
      succinate, and tresyl chloride. Transduction efficiency was assessed on Caco-2
      cells. In vitro stability of viruses in simulated gastric fluid, pancreatic
      fluid, and bile was assessed by serial dilution on 293 cells. Transduction
      efficiency in vivo was determined by oral administration of 1 x 10(12) particles
      of unmodified or PEGylated virus to fasted Sprague-Dawley rats. RESULTS: Titers
      of unmodified virus declined to undetectable levels after 40 min in simulated
      gastric fluid while the infectious titer of the modified vectors did not change
      for 3 h. Similar results were seen with simulated pancreatic fluid. PEGylation
      also enhanced adenoviral transduction efficiency in Caco-2 cells by a factor of
      20. PEGylation enhanced adenovirus transduction efficiency 10- to 40-fold in vivo
      in intestinal segments that do not express significant amounts of adenovirus
      receptors (jejunum, colon) with transgene expression located in the crypt
      regions. CONCLUSIONS: PEGylated adenoviruses are suitable gene delivery vehicles
      for oral administration.

PMID- 14567639
TI  - Investigations into the stabilization of drugs by sugar glasses: III. The
      influence of various high-pH buffers.
AB  - PURPOSE: To study the effect of the high-pH buffers ammediol, borax, CHES, TRIS,
      and Tricine on the glass transition temperature of the freeze concentrated
      fraction (Tg') of trehalose/buffer and inulin/buffer solutions at pH 6.0 and pH
      9.8. Also, the glass transition temperature (Tg) of sugar glasses obtained after
      freeze drying of these solutions was elucidated. Additionally, the effect
      occurring during the freezing process on the pH of the various buffers was
      investigated. Furthermore, the stability of alkaline phosphatase (AP)
      incorporated in these sugar glasses prepared from solutions at pH 9.8 was
      evaluated. METHODS: The Tg' and Tg were measured using differential scanning
      calorimetry (DSC), and the change of pH during freezing was estimated by using an
      indicator solution added to the respective solutions. The enzymatic activity of
      AP after freeze drying and storage at 60 degrees C was evaluated by an enzymatic
      activity assay. RESULTS: It was found that the Tg' and Tg of the samples
      investigated are strongly influenced by the presence of the buffer. On freezing,
      only minor changes of the pH were observed. The samples with the lowest Tg and
      the samples containing buffers that formed complexes with the sugars showed the
      poorest stability of the AP. CONCLUSIONS: The stabilizing capacities of sugars
      that are currently recognized as excellent stabilizers for proteins during drying
      and storage can be completely lost if certain high-pH buffers such as ammediol,
      borax, and TRIS are used at high concentrations. Loss of stabilizing capacities
      can be ascribed to strong depression of the Tg' and Tg or to complex formation.

PMID- 14567641
TI  - Analysis of hepatic disposition of galactosylated cationic liposome/plasmid DNA
      complexes in perfused rat liver.
AB  - PURPOSE: To determine the intrahepatic disposition characteristics of
      galactosylated liposome/plasmid DNA (pDNA) complexes in perfused rat liver.
      METHODS: Galactosylated liposomes containing N-[1-(2,3-dioleyloxy)propyl]-N,N,N
      trimethylammonium chloride (DOTMA), cholesterol (Chol), and cholesten-5-yloxy-N
      14-[(1-imino-2-D-thiogalactosylethyl)amino]butyl] formamide (Gal-C4-Chol) were
      prepared. The liposome/[32P]-labeled pDNA complexes were administered to perfused
      liver, and the venous outflow patterns were analyzed based on a two-compartment
      dispersion model. RESULTS: The single-pass hepatic extraction of pDNA complexed
      with DOTMA/Chol/Gal-C4-Chol liposomes was greater than that with control
      DOTMA/Chol liposomes. A two-compartment dispersion model revealed that both the
      tissue binding and cellular internalization rate were higher for the
      DOTMA/Chol/Gal-C4-Chol liposome complexes compared with the control liposome
      complexes. The tissue binding was significantly reduced by the presence of 20 mM
      galactose. When their cellular localization in the perfused liver at 30 min
      postinjection was investigated, it was found that the parenchymal uptake of the
      DOTMA/Chol/Gal-C4-Chol liposome complexes was greater than that of the control
      liposome complexes. The parenchymal cell/ nonparenchymal cell uptake ratio was as
      high as unity. CONCLUSION: Galactosylation of the liposome/pDNA complexes
      increases the tissue binding and internalization rate via an asialoglycoprotein
      receptor-mediated process. Because of the large particle size of the complexes
      (approximately 150 nm), however, penetration across the fenestrated sinusoidal
      endothelium appears to be limited.

PMID- 14567642
TI  - Intestinal lymphatic transport of halofantrine occurs after oral administration
      of a unit-dose lipid-based formulation to fasted dogs.
AB  - PURPOSE: To examine whether the small quantities of lipid present in unit-dose
      microemulsion formulations comprising medium- (C8-10) or long-chain (C18)
      glyceride lipids can stimulate the intestinal lymphatic transport of halofantrine
      (Hf), a model lymphatically transported drug. METHODS: Hf (50 mg) was
      administered to thoracic lymph duct- and cephalic vein-cannulated fasted
      greyhound dogs. Drug was formulated as a single soft gelatin capsule containing
      approximately 1 g of a microemulsion preconcentrate based on either medium- or
      long-chain glycerides. Thoracic lymph was collected, and systemic plasma samples
      taken over 10 h postdose. RESULTS: The extent of lymphatic transport of Hf after
      administration of the long-chain lipid formulation was high (28.3% of dose), and
      significantly higher than that seen after administration of the medium-chain
      formulation (5.0% of dose). Plasma levels of Hf were not significantly different
      across the two formulations when assessed by AUC0-10h. CONCLUSIONS: This is the
      first study to demonstrate that the small amounts of lipid present within a
      single lipid-based dose form can support substantial intestinal lymphatic
      transport in the fasted state. Furthermore, microemulsions based on long-chain
      glycerides appear to be more effective with respect to lymphatic transport than
      the equivalent medium-chain formulation.

PMID- 14567644
TI  - The effect of blood sampling site and physicochemical characteristics of drugs on
      bioavailability after nasal administration in the sheep model.
AB  - PURPOSE: Investigate the effect of blood sampling site and physicochemical
      characteristics of drugs on the pharmacokinetic (PK) parameters obtained after
      intravenous and nasal administration in sheep and compare results with computer
      simulations. METHODS: Three drugs, insulin, morphine, and nicotine, were
      administered nasally and by intravenous (IV) injection to sheep, and serial blood
      samples collected concurrently from the carotid artery (insulin, morphine) or
      cephalic vein (nicotine) and jugular vein. Plasma drug concentrations were
      measured, and pharmacokinetic and statistical analyses performed, to evaluate
      sampling site differences. RESULTS: After nasal insulin, bioavailabilities
      calculated from the two blood sampling site data were comparable. In contrast,
      apparent bioavailabilities following nasal morphine or nicotine were
      significantly higher when sampling was from the jugular vein. These results were
      supported by computer simulations. These observations are attributed to the
      greater effects of noninstantaneous mixing of drugs for jugular vein sampling
      following nasal dosing, compared to the other sampling sites, which is
      significant for drugs that are rapidly and well absorbed and that have a high
      volume of distribution (Vd). CONCLUSION: The results clearly show that the
      characteristics of the drug and the blood sampling site can have a significant
      effect on the pharmacokinetic results obtained after nasal administration in
      sheep.

PMID- 14567643
TI  - Novel gastroretentive dosage forms: evaluation of gastroretentivity and its
      effect on levodopa absorption in humans.
AB  - PURPOSE: To design novel expandable gastroretentive dosage form (GRDFs) and
      evaluate their gastroretentive properties. Then, to assess the pharmacokinetics
      of levodopa compounded in such a GRDF in healthy volunteers. METHODS: Thin (<0.07
      cm), large-dimensioned (> or = 5 x 2.1 cm), multi layer dosage forms (DFs) with
      different rigid polymeric matrices an mechanical properties were folded into
      gelatin capsules and wer administered to healthy volunteers with a light
      breakfast. GRDF unfolding and physical integrity were evaluated in vitro and in
      vivo (by gastroscopy and radiology). The pharmacokinetics of levodopa GRDF were
      compared to Sinemet CR in a crossover design. RESULTS: The combination of
      rigidity and large dimension of the GRDFs was a decisive parameter to ensure
      prolonged gastroretentivity (> or = 5 h). Large-dimension DFs lacking rigidity
      had similar gastroretentivity as a nondisintegrating tablet (10 mm). The GRDF
      rapidly unfolded and maintained their mechanical integrity. The absorption phase
      of levodopa was significantly prolonged following GRDF administration in
      comparison to Sinemet CR. CONCLUSIONS: The combination of size and rigidity of
      the novel GRDF enables a significant extension of the absorption phase of a
      narrow absorption window drug such as levodopa. This approach is an important
      step toward the implementation of such GRDFs in the clinical setting.

PMID- 14567645
TI  - Evaluation of an aerosolized selective COX-2 inhibitor as a potentiator of
      doxorubicin in a non-small-cell lung cancer cell line.
AB  - PURPOSE: To evaluate the in vitro effects of an aerosolized cyclooxygenase-2 (COX
      2) inhibitor, nimesulide, on the cytotoxicity and apoptotic response of
      doxorubicin against the human lung adenocarcinoma cell line A549. METHODS:
      Nimesulide was formulated into a metered dose inhaler (MDI) formulation and
      characterized for aerodynamic particle size and medication delivery. The in vitro
      cytotoxicity of nimesulide-MDI in the presence or absence of doxorubicin was
      assessed by using the six-stage viable impactor by an already standardized
      method. Induction of apoptosis in A549 cells by nimesulide (nonaerosolized or
      aerosolized) in combination with doxorubicin was evaluated by established
      techniques such as caspase-3 estimation and terminal deoxynucleotidyl transferase
      mediated nick end labeling (TUNEL) staining. Finally, to understand the mechanism
      of action, the influence of different treatments on the expression of COX-2 and
      peroxisome proliferator-activated receptor-gamma (PPAR-gamma) in A549 cells was
      studied by immunoblotting. RESULTS: The nimesulide-MDI formulation had a mass
      median aerodynamic diameter (MMAD) of 1.1 microm, (GSD = 2.8) and a medication
      delivery of 51 microg/shot. Nimesulide-MDI (40 shots) in combination with
      doxorubicin (0.01 microg/ml) had a cell kill of more than 60% as determined by in
      vitro cytotoxicity assay. The specific caspase-3 activity in A549 cells treated
      with nimesulide (40 microg/ml) and doxorubicin (0.25 microg/ml) in combination
      was 3 and 5 times higher than doxorubicin and nimesulide, respectively. Further,
      TUNEL staining showed apoptosis in over 30% of A549 cells treated with
      aerosolized nimesulide and doxorubicin combination vs. negligible as seen in
      cells treated individually. The expression of COX-2 was not altered in control or
      treatments, whereas PPAR-gamma was expressed only in the combination treatment.
      CONCLUSION: Our results indicate that aerosolized nimesulide significantly
      enhances doxorubicin activity against A549 cells, and the enhanced cytotoxicity
      was probably mediated via a COX-2-independent mechanism.

PMID- 14567646
TI  - Iontophoretic in vivo transdermal delivery of beta-blockers in hairless rats and
      reduced skin irritation by liposomal formulation.
AB  - PURPOSE: To demonstrate the in vivo transdermal delivery and establish the
      comparative pharmacokinetics of five beta-blockers in hairless rat. METHODS:
      Intravenous dosing was initially done via jugular cannula. For iontophoretic
      delivery, current (0.1 mA/cm2) was applied for 2 h through a drug reservoir patch
      containing the beta-blocker (10 mg/ml). Blood samples were collected and analyzed
      by stereoselective HPLC assays. Any irritation resulting from patch application
      was quantified by a chromameter. Multilamellar liposomal formulation was prepared
      by the thin-film hydration method and converted to unilamellar liposomes by
      extrusion. RESULTS: With transdermal iontophoresis, therapeutically relevant
      amounts of propranolol (83.78 +/- 7.4 ng/ml) were delivered within an hour and
      lasted for up to 4 h. Cmax (185.1 +/- 56.8 ng/ml) was reached at hour 3. A
      significantly higher amount (p < 0.05) of sotalol HCl was delivered compared to
      other beta-blockers. There was no significant difference in the S/R ratio of AUC0
      t for enantiomers after both intravenous and transdermal delivery. Skin
      irritation was significantly reduced (p < 0.05) when a liposomal formulation of
      the propranolol base was used rather than the base itself. CONCLUSIONS: The
      comparative pharmacokinetics of intravenous and transdermal iontophoretic
      delivery of five beta-blockers in hairless rats was established. It was shown
      that there is no stereoselective permeation.

PMID- 14567647
TI  - Effect of vehicle pretreatment on the flux, retention, and diffusion of topically
      applied penetrants in vitro.
AB  - PURPOSE: The flux of a topically applied drug depends on the activity in the skin
      and the interaction between the vehicle and skin. Permeation of vehicle into the
      skin can alter the activity of drug and the properties of the skin barrier. The
      aim of this in vitro study was to separate and quantify these effects. METHODS:
      The flux of four radiolabeled permeants (water, phenol, diflunisal, and diazepam)
      with log Koct/water values from 1.4 to 4.3 was measured over 4 h through heat
      separated human epidermis pretreated for 30 min with vehicles having Hildebrand
      solubility parameters from 7.9 to 23.4 (cal/cm3)1/2. RESULTS: Enhancement was
      greatest after pretreatment with the more lipophilic vehicles. A synergistic
      enhancement was observed using binary mixtures. The flux of diazepam was not
      enhanced to the same extent as the other permeants, possibly because its
      partitioning into the epidermis is close to optimal (log Koct 2.96). CONCLUSION:
      An analysis of the permeant remaining in the epidermis revealed that the
      enhancement can be the result of either increased partitioning of permeant into
      the epidermis or an increasing diffusivity of permeants through the epidermis.

PMID- 14567648
TI  - Transdermal reverse iontophoresis of valproate: a noninvasive method for
      therapeutic drug monitoring.
AB  - PURPOSE: The objectives of this work were (a) to explore the potential of
      transdermal reverse iontophoresis for therapeutic drug monitoring and (b) to
      develop an "internal standard" calibration procedure so as to render the
      technique completely noninvasive. METHODS: A series of in vitro iontophoresis
      experiments was performed in which the subdermal concentration of sodium
      valproate was varied from 21 microM to 1 mM. Glutamic acid was also introduced
      into the subdermal donor at a fixed concentration to act as an "internal
      standard" for the calibration method. RESULTS: Both valproate and glutamate
      anions were recovered, as expected, at the anodal receptor chamber. The
      iontophoretic extraction flux of valproate was linearly correlated with the
      subdermal concentration. Glutamate flux was constant. It follows that the ratio
      of extracted fluxes (valproate/glutamate) was directly dependent upon (a) the
      subdermal valproate concentration and (b) the subdermal concentration ratio
      (valproate/glutamate), offering a means, thereby, to a completely noninvasive
      methodology. CONCLUSIONS: This work demonstrates the potential of reverse
      iontophoresis for noninvasive therapeutic monitoring. The simultaneous
      quantification of the analyte of interest and of an "internal standard" renders
      the withdrawal of a blood sample unnecessary.

PMID- 14567649
TI  - The politics and science of "reparative therapy".

PMID- 14567650
TI  - Can some gay men and lesbians change their sexual orientation? 200 participants
      reporting a change from homosexual to heterosexual orientation.
AB  - Position statements of the major mental health organizations in the United States
      state that there is no scientific evidence that a homosexual sexual orientation
      can be changed by psychotherapy, often referred to as "reparative therapy." This
      study tested the hypothesis that some individuals whose sexual orientation is
      predominantly homosexual can, with some form of reparative therapy, become
      predominantly heterosexual. The participants were 200 self-selected individuals
      (143 males, 57 females) who reported at least some minimal change from homosexual
      to heterosexual orientation that lasted at least 5 years. They were interviewed
      by telephone, using a structured interview that assessed same sex attraction,
      fantasy, yearning, and overt homosexual behavior. On all measures, the year prior
      to the therapy was compared to the year before the interview. The majority of
      participants gave reports of change from a predominantly or exclusively
      homosexual orientation before therapy to a predominantly or exclusively
      heterosexual orientation in the past year. Reports of complete change were
      uncommon. Female participants reported significantly more change than did male
      participants. Either some gay men and lesbians, following reparative therapy,
      actually change their predominantly homosexual orientation to a predominantly
      heterosexual orientation or some gay men and women construct elaborate self
      deceptive narratives (or even lie) in which they claim to have changed their
      sexual orientation, or both. For many reasons, it is concluded that the
      participants' self-reports were, by-and-large, credible and that few elaborated
      self-deceptive narratives or lied. Thus, there is evidence that change in sexual
      orientation following some form of reparative therapy does occur in some gay men
      and lesbians.

PMID- 14567651
TI  - Life on the seesaw: a qualitative study of suicide resiliency factors for young
      gay men.
AB  - While considerable research has highlighted the factors that increase gay youth
      suicide risk, there has been much less emphasis on protective factors. Using
      grounded theory methodology, we explored the suicide resiliency in eight young
      gay men in Aotearoa/New Zealand. Common themes emerged, including positive social
      norms and conditions, high levels of support, identification with role models and
      high self-esteem. These were integrated with "known" risk factors to form the
      Seesaw Model of Gay Male Suicide. This model demonstrates that the balance
      between risk and resiliency may be the key to gay suicide. Depending on the
      balance of these factors, youth might either be resilient, attempt suicide, or
      teeter somewhere in between. The current findings indicate that gay youth suicide
      prevention requires efforts to increase resiliency factors for this group.

PMID- 14567652
TI  - Correlates of gay and lesbian couples' relationship satisfaction and relationship
      dissolution.
AB  - A sample of committed gay and lesbian cohabiting couples engaged in two
      conversations after being apart for at least 8 hours: (a) an events of the day
      conversation and (b) a conflict resolution conversation. Physiological data were
      collected during the conversations and a videotape record was made. Couples
      viewed the videotapes and rated their affect during the interaction. The video
      records were coded with a system that categorized specific affects displayed.
      Models derived from physiology, from the perception of interaction, and from
      specific affective behavior were related to relationship satisfaction, and to the
      prediction of relationship dissolution over a 12-year period. Results supported
      previous findings that satisfaction and stability in gay and lesbian
      relationships are related to similar emotional qualities as in heterosexual
      relationships.

PMID- 14567653
TI  - A critical appraisal of assimilationist and radical ideologies underlying same
      sex marriage in LGBT communities in the United States.
AB  - Debates over same-sex marriage have reached the main stage of contemporary U.S.
      politics. The purpose of this essay is to identify and examine how sexual
      ideologies in U.S. LGBT communities inform and influence relationship
      construction in general and same-sex marriage in particular. To accomplish this,
      we first discuss the nature of sexual ideologies. Next, we identify current
      sexual ideologies in LGBT communities and examine some of their fundamental
      features and their implications for relationship construction with a focus on
      same-sex marriage. We conclude with a discussion of what is potentially gained
      and lost by same-sex matrimonial bonds and explore some of the prospects of
      relationship construction within LGBT communities in the future.

PMID- 14567654
TI  - Observing gay, lesbian and heterosexual couples' relationships: mathematical
      modeling of conflict interaction.
AB  - Two samples of committed gay and lesbian cohabiting couples and two samples of
      married couples (couples in which the woman presented the conflict issue to the
      man, and couples in which the man presented the conflict issue to the woman)
      engaged in three conversations: (1) an events of the day conversation (after
      being apart for at least 8 hours), (2) a conflict resolution conversation, and
      (3) a pleasant topic conversation. The observational data were coded with a
      system that categorized specific affects displayed. Data were weighted and two
      time-series created, one for the husband and one of the wife. The time series
      were modeled with nonlinear difference equations (Cook et al., 1995), and
      parameters were estimated that indexed uninfluenced steady state, influenced
      steady state, emotional inertia, repair effectiveness and threshold, and the
      power of positive and negative affect of one partner to affect the other partner.

PMID- 14567655
TI  - Lesbian shame: its relationship to identity integration and attachment.
AB  - Using self-report measures, this survey study explored the relationship between
      internalized shame and both lesbian identity integration and attachment styles.
      Compared to other research, this U.S. sample of 317 highly educated, mid-life,
      mostly European-American self-identitied lesbians reported higher levels of
      internalized shame, lesbian identity integration, and dismissing attachment. As
      predicted, shame scores decreased as lesbian identity integration increased.
      Likewise, high levels of secure attachment were associated with less shame while
      high levels of fearful and preoccupied attachment were associated with greater
      shame. Contrary to prediction, high levels of dismissing attachment were
      associated with greater shame. These results suggest the pervasive effects of
      shame even for a sample of educationally and occupationally successful lesbians.

PMID- 14567656
TI  - Representations of desires in some recent gay Asian-American writings.
AB  - This article explores conceptions of same-sex sexual behavior and desires by
      American gay males who grew up in Pacific Island or Asian societies. In the
      absence of systematic survey data, representations, which are not assumed to be
      autobiographical, by two South Asian emigres to Canada (Badruddin Khan and Shyam
      Selvadurai), two second generation Filipino-Americans (Joel Tan and Ricardo
      Ramos), a second generation Chinese-Hawaiian (Norman Wong) and three men of
      Chinese descent born and raised in Southeast Asia (Lawrence Chua, Justin Chin,
      and T. C. Huo) are examined. The unsatisfying script of sexual submission of
      Asians to whites is particularly central, except for the South Asians. These
      books provide recurrent evidence of role distance, of switching roles (often
      without rewriting a dominance-submission conception of insertion-reception) and
      of some degree of reconceiving the (sexual) self.

PMID- 14567657
TI  - Searching the databases: a quick look at Amazon and two other online catalogues.
AB  - The Amazon Online Catalogue was compared with the Library of Congress Catalogue
      and the British Library Catalogue, both also available online, by searching on
      both neutral (Gay, Lesbian, Homosexual) and pejorative (Perversion, Sex Crime)
      subject terms, and also by searches using Boolean logic in an attempt to identify
      Lesbian Fiction items and religion-based anti-gay material. Amazon was much more
      likely to be the first port of call for non-academic enquiries. Although
      excluding much material necessary for academic research, it carried more
      information about the individual books and less historical homophobic baggage in
      its terminology than the great national catalogues. Its back catalogue of second
      hand books outnumbered those in print. Current attitudes may partially be gauged
      by the relative numbers of titles published under each heading--e.g., there may
      be an inverse relationship between concern about child sex abuse and homophobia,
      more noticeable in U.S. because of the activities of the religious right.

PMID- 14567658
TI  - Passports, prescriptions and professional development at the 2003 BEVA congress.

PMID- 14567659
TI  - Vet struck off for false export certification.

PMID- 14567660
TI  - Application for readmission to the Register refused.

PMID- 14567661
TI  - The New Veterinary College, Edinburgh, 1873 to 1904.
AB  - This year's BVA Congress takes place in Edinburgh, home of the Royal (Dick)
      School of Veterinary Studies. However, the Scottish capital has been host to more
      than one veterinary school over the years, as Colin Warwick and Alastair
      MacDonald explain.

PMID- 14567662
TI  - Outbreak of dysautonomia (Key-Gaskell syndrome) in a closed colony of pet cats.
AB  - Six of eight pet cats in a closed colony developed overt signs of dysautonomia
      over a period of seven days; two of them died and one was euthanased.
      Dysautonomia was confirmed histopathologically in two of these cats, and in the
      others the diagnosis was based on the characteristic clinical and radiographic
      findings. In the two apparently unaffected cats abnormal oesophageal motility was
      demonstrated by fluoroscopy, suggesting that there may be a subclinical form of
      the disease. The surviving cats had higher and more variable heart rates (mean
      165 bpm) than the non-survivors (mean 121 bpm).

PMID- 14567663
TI  - Survey of the views of graduates (1993 to 1997) on the undergraduate veterinary
      clinical curriculum in the British Isles.
AB  - In 1998 a questionnaire was sent to graduates from all the veterinary schools in
      Great Britain and Ireland who had obtained their veterinary degree within the
      previous five years, to assess their opinions of the undergraduate clinical
      veterinary curriculum. Ninety-five per cent of the graduates who responded were
      working full time in veterinary practice, with small animal work occupying 90 per
      cent of them for a median of 70 per cent of their time. Their assessment of the
      curriculum suggested that they were generally satisfied, but that there were some
      subjects they considered important in which the teaching and extramural studies
      had failed to provide adequate learning opportunities. Twelve subjects were rated
      as 'very important', two subjects, small animal medicine and anaesthesia, were
      considered to be 'very well' taught, and extramural studies were considered to be
      'very useful' for three subjects, small animal surgery, cattle medicine and
      cattle surgery. The survey provided evidence that graduates are keen to continue
      learning and specialise after they graduate.

PMID- 14567664
TI  - Disease and mortality among great bustards (Otis tarda) at Whipsnade Wild Animal
      Park, 1989 to 1999.
AB  - Between 1989 and 1999, 351 clinical examinations and six postmortem examinations
      were made on the six great bustards (Otis tarda) maintained at the Whipsnade Wild
      Animal Park. Soft tissue-related traumatic injuries accounted for 35 per cent of
      all the clinical findings, musculoskeletal disorders accounted for 26 per cent,
      and lameness was one of the main reasons for a veterinary examination. Poor
      condition accounted for 30 per cent of the clinical findings and was associated
      with periods of cold wet weather during the winter and spring; the affected birds
      were isolated and provided with nutritional support. Haemosiderosis and
      haemochromatosis were observed in four of the five birds from which samples were
      taken for histopathology.

PMID- 14567665
TI  - Survey of veterinary practitioners on PMWS and PDNS in the UK.

PMID- 14567666
TI  - Multi-antigen ELISA for enhanced diagnosis of tuberculosis in badgers.

PMID- 14567667
TI  - Isolation of Malassezia pachydermatis from the skin of captive rhinoceroses.

PMID- 14567668
TI  - FMD control strategies.

PMID- 14567669
TI  - VTEC O157 in cattle.

PMID- 14567670
TI  - Feline dysautonomia website.

PMID- 14567671
TI  - Antibiotic growth promoters.

PMID- 14567672
TI  - New H1N2 and H3N1 influenza viruses in Taiwanese pig herds.

PMID- 14567673
TI  - STOP proteins.
AB  - Microtubules assembled from purified tubulin in vitro are labile, rapidly
      disassembling when exposed to a variety of depolymerizing conditions such as cold
      temperature. In contrast, in many cell types, microtubules seem to be unaffected
      when the cell is exposed to the cold. This resistance of microtubules to the cold
      has been intriguing because the earliest and by far most studied microtubule
      associated proteins such as MAP2 and tau are devoid of microtubule cold
      stabilizing activity. Over the past several years, it has been shown that
      resistance of microtubules to the cold is largely due to polymer association with
      a class of microtubule-associated proteins called STOPs. STOPs are calmodulin
      binding and calmodulin-regulated proteins which, in mammals, are encoded by a
      single gene but exhibit substantial cell specific variability due to mRNA
      splicing and alternative promoter use. STOP microtubule stabilizing activity has
      been ascribed to two classes of new bifunctional calmodulin- and microtubule
      binding motifs, with distinct microtubule binding properties in vivo. STOPs seem
      to be restricted to vertebrates and are composed of a conserved domain split by
      the apparent insertion of variable sequences that are completely unrelated among
      species. Recently, STOP suppression in mice has been found to induce synaptic
      defects associated with neuroleptic-sensitive behavioral disorders. Thus, STOPs
      are important for synaptic plasticity. Additionally, STOP-deficient mice may
      yield a pertinent model for the study of neuroleptics in illnesses such as
      schizophrenia, currently thought to result from defects in synapse function.

PMID- 14567674
TI  - Structural evidence for a 1,2-enediolate intermediate in the reaction catalyzed
      by 3-keto-L-gulonate 6-phosphate decarboxylase, a member of the orotidine 5'
      monophosphate decarboxylase suprafamily.
AB  - 3-Keto-L-gulonate 6-phosphate decarboxylase (KGPDC) and orotidine 5'-phosphate
      decarboxylase (OMPDC) are members of an enzyme suprafamily, the OMPDC
      suprafamily, because they are homologous enzymes that catalyze mechanistically
      distinct reactions using different substrates. KGPDC catalyzes the Mg(2+) ion
      dependent decarboxylation of 3-keto-L-gulonate 6-phosphate to yield L-xylulose 5
      phosphate and CO(2); OMPDC catalyzes the metal ion-independent decarboxylation of
      OMP to UMP and CO(2). Structural studies have shown that KGPDC and OMPDC share
      several strictly conserved active site residues that are used differently by each
      enzyme to catalyze their mechanistically distinct reactions. Although the
      mechanism of the KGPDC-catalyzed reaction has yet to be elucidated, it is thought
      to proceed via a Mg(2+) ion-stabilized 1,2-enediolate intermediate. Here we
      report the crystal structures of KGPDC complexed with L-gulonate 6-phosphate, L
      threonohydroxamate 4-phosphate, and L-xylitol 5-phosphate, analogues of the
      substrate, enediolate intermediate, and product, as well as with the product, L
      xylulose 5-phosphate, at 1.2, 1.8, 1.7, and 1.8 A resolution, respectively. These
      structures support a mechanism that involves the formation of a cis-1,2
      enediolate intermediate. Contrary to expectations, the geometry of the
      intermediate does not involve bidentate coordination of both enediolate oxygen
      atoms to the Mg(2+) ion but rather involves only the coordination of the oxygen
      on C2 to the Mg(2+) ion. The oxygen atom on C1 instead forms hydrogen bonds to
      both Lys64 and Asp67, two strictly conserved active site residues. Lys64 also
      interacts with the oxygen on C2 and may serve to stabilize a cis conformation of
      the 1,2-enediolate. These structures also implicate His136 to be the general acid
      that protonates the 1,2-enediolate intermediate. This study further demonstrates
      that multiple unrelated enzyme functions can evolve from a single active site
      architecture without regard for substrate binding affinity or mechanism.

PMID- 14567675
TI  - Conformational change in the NADP(H) binding domain of transhydrogenase defines
      four states.
AB  - Proton-translocating transhydrogenase (TH) couples direct and stereospecific
      hydride transfer between NAD(H) and NADP(H), bound to soluble domains dI and
      dIII, respectively, to proton translocation across a membrane bound domain, dII.
      The reaction occurs with proton-gradient coupled conformational changes, which
      affect the energetics of substrate binding and interdomain interactions. The
      crystal structure of TH dIII from Rhodospirillum rubrum has been determined in
      the presence of NADPH (2.4 A) and NADP (2.1 A) (space group P6(1)22). Each
      structure has two molecules in the asymmetric unit, differing in the conformation
      of the NADP(H) binding loop D. In one molecule, loop D has an open conformation,
      with the B face of (dihydro)nicotinamide exposed to solvent. In the other
      molecule, loop D adopts a hitherto unobserved closed conformation, resulting in
      close interactions between NADP(H) and side chains of the highly conserved
      residues, betaSer405, betaPro406, and betaIle407. The conformational change
      shields the B face of (dihydro)nicotinamide from solvent, which would block
      hydride transfer in the intact enzyme. It also alters the environments of
      invariant residues betaHis346 and betaAsp393. However, there is little difference
      in either the open or the closed conformation upon change in oxidation state of
      nicotinamide, i.e., for NADP vs. NADPH. Consequently, the occurrence of two loop
      D conformations for both substrate oxidation states gives rise to four states:
      NADP-open, NADP-closed, NADPH-open, and NADPH-closed. Because these states are
      distinguished by protein conformation and by net charge they may be important in
      the proton translocating mechanism of intact TH.

PMID- 14567676
TI  - Structure determination and dynamics of peptides overlapping the catalytic
      hairpin of the Ras-specific GEF Cdc25(Mm).
AB  - Ras proteins are small G proteins playing a major role in eukaryotic signal
      transduction. Guanine nucleotide exchange factors (GEF) stimulate GDP/GTP
      exchange, resulting in the formation of the active Ras-GTP complex. In mammalian
      cells, two major Ras-specific GEF exist: Sos-like and Cdc25-like. To date,
      structural data are available only for Cdc25(Mm). We designed and synthesized
      Cdc25(Mm)-derived peptides spanning residues corresponding to the hSos1 HI
      helical hairpin that has been implicated in the GEF catalytic mechanism. NMR
      experiments on a chemically synthesized Cdc25(Mm)(1178-1222) peptide proved that
      helix I readily reaches a conformation very similar to the corresponding helix in
      hSos1, while residues corresponding to helix H in hSos1 show higher
      conformational flexibility. Molecular dynamics studies with the appropriate
      solvent model showed that different conformational spaces are available for the
      peptide. Since helix H is making several contacts with Ras and a Cdc25(Mm)(1178
      1222) peptide is able to bind nucleotide-free Ras in a BIAcore assay, the peptide
      must be able to obtain the proper Ras-interacting conformation, at least
      transiently. These results indicate that rational design and improvement of the
      Ras-interacting peptides should take into account conformational and flexibility
      features to obtain molecules with the appropriate biochemical properties.

PMID- 14567677
TI  - A mechanism for P-glycoprotein-mediated apoptosis as revealed by verapamil
      hypersensitivity.
AB  - Selection of tumor cell lines with anticancer drugs has led to the appearance of
      multidrug-resistant (MDR) subclones with P-glycoprotein 1 (P-gp1) expression.
      These cells are cross-resistant to several structurally and functionally
      dissimilar drugs. Interestingly, in the process of gaining resistance, MDR cells
      become hypersensitive or collaterally sensitive to membrane-active agents, such
      as calcium channel blockers, steroids, and local anaesthetics. In this report,
      hypersensitivity to the calcium channel blocker, verapamil, was analyzed in
      sensitive and resistant CHO cell lines. Our results show that treatment with
      verapamil preferentially induced apoptosis in MDR cells compared to drug
      sensitive cells. This effect was independent of p53 activity and could be
      inhibited by overexpression of the Bcl-2 gene. The induction of apoptosis by
      verapamil had a biphasic trend in which maximum cell death occurred at 10 microM,
      followed by improved cell survival at higher concentrations (50 microM). We
      correlated this effect to a similar biphasic trend in P-gp1 ATPase activation by
      verapamil in which low concentrations of verapamil (10 microM) activated ATPase,
      followed by inhibition at higher concentrations. To confirm the relationship
      between apoptosis and ATPase activity, we used two inhibitors of P-gp1 ATPase,
      PSC 833 and ivermectin. These ATPase inhibitors reduced hypersensitivity to
      verapamil in MDR cells. In addition, low concentrations of verapamil resulted in
      the production of reactive oxygen species (ROS) in MDR cells. Taken together,
      these results show that apoptosis was preferentially induced by P-gp1 expressing
      cells exposed to verapamil, an effect that was mediated by ROS, produced in
      response the high ATP demand by P-gp1.

PMID- 14567678
TI  - Biochemical and structural characterization of the interaction of memapsin 2
      (beta-secretase) cytosolic domain with the VHS domain of GGA proteins.
AB  - Memapsin 2 (beta-secretase) is a membrane-associated aspartic protease that
      initiates the hydrolysis of beta-amyloid precursor protein (APP) leading to the
      production of amyloid-beta and the onset of Alzheimer's disease (AD). Both
      memapsin 2 and APP are transported from the cell surface to endosomes where APP
      hydrolysis takes place. Thus, the intracellular transport mechanism of memapsin 2
      is important for understanding the pathogenesis of AD. We have previously shown
      that the cytosolic domain of memapsin 2 contains an acid-cluster-dileucine (ACDL)
      motif that binds the VHS domain of GGA proteins (He et al. (2002) FEBS Lett. 524,
      183-187). This mechanism is the presumed recognition step for the vesicular
      packaging of memapsin 2 for its transport to endosomes. The phosphorylation of a
      serine residue within the ACDL motif has been reported to regulate the recycling
      of memapsin 2 from early endosomes back to the cell surface. Here, we report a
      study on the memapsin 2/VHS domain interaction. Using isothermal titration
      calorimetry, the dissociation constant, K(d), values are 4.0 x 10(-4), 4.1 x 10(
      4), and 3.1 x 10(-4) M for VHS domains from GGA1, GGA2, and GGA3, respectively.
      With the serine residue replaced by phosphoserine, the K(d) decreased about 10-,
      4-, and 14-fold for the same three VHS domains. A crystal structure of the
      complex between memapsin 2 phosphoserine peptide and GGA1 VHS was solved at 2.6 A
      resolution. The side chain of the phosphoserine group does not interact with the
      VHS domain but forms an ionic interaction with the side chain of the C-terminal
      lysine of the ligand peptide. Energy calculation of the binding of native and
      phosphorylated peptides to VHS domains suggests that this intrapeptide ionic bond
      in solution may reduce the change in binding entropy and thus increase binding
      affinity.

PMID- 14567679
TI  - The G protein-coupled receptor GPR4 suppresses ERK activation in a ligand
      independent manner.
AB  - The lysophospholipids, lysophosphatidic acid, sphingosine-1-phosphate, and
      sphingosylphosphorylcholine (SPC), are bioactive lipid molecules that regulate
      diverse biological processes. Although the specific G protein-coupled receptors
      for lysophosphatidic acid and sphingosine-1-phosphate have been well
      characterized, much less is known of the SPC receptors. It has been reported that
      ovarian cancer G protein-coupled receptor 1 (OGR1) is a high affinity receptor
      for SPC, and its closely related homologue GPR4 is a high affinity receptor for
      SPC with low affinity for lysophosphatidylcholine (LPC). However, in a functional
      assay to examine the specificity of ligand binding, we found that neither SPC nor
      LPC, or other related lysophospholipids, induced internalization of GPR4 from the
      plasma membrane. In agreement, these lysolipids also did not induce translocation
      of beta-arrestin2-GFP from the cytosol to the plasma membrane in GPR4 expressing
      cells. However, when these cells were cotransfected with G protein-coupled
      receptor kinase 2, in the absence of added ligands, beta-arrestin2-GFP
      accumulated in cytoplasmic vesicles, reminiscent of vesicular labeling usually
      observed after agonist stimulation of GPCRs. In addition, neither SPC nor LPC
      stimulated the binding of GTPgammaS to membranes prepared from GPR4 expressing
      cells and did not activate ERK1/2. Surprisingly, enforced expression of GPR4
      inhibited activation of ERK1/2 induced by several stimuli, including SPC,
      sphingosine-1-phosphate, and even EGF. Collectively, our results suggest that SPC
      and LPC are not the ligands for GPR4 and that this receptor may constitutively
      inhibit ERK1/2 activation.

PMID- 14567680
TI  - Consequences of single-site mutations in the intestinal fatty acid binding
      protein.
AB  - The intestinal fatty acid binding protein (IFABP) is a small (15 kDa) protein
      consisting mostly of 10 antiparallel beta-strands (A-J) and a small helical
      region that serves as a portal for the ligand. Two beta-sheet structures (strands
      A-E and F-J) surround a cavity into which the ligand binds. In this work, we
      investigated how changes in the side chains of specific residues are propagated
      through the structure. To determine what these changes were and how they relate
      to changes in stability, (15)N chemical shift perturbations were measured and
      compared to those of the wild-type protein. Seven mutations, five of which change
      either valine or leucine to glycine, have been examined. All these mutants were
      less stable than wild-type IFABP, suggesting some structural changes. For five of
      the mutants, the data suggest that destabilization of a small region of the
      protein propagates throughout the structure, resulting in an overall decrease in
      stability. In two (Leu38Gly and Leu89Gly), the loss of cooperativity in the
      equilibrium denaturation curves suggests that the destabilization of one region
      may not be transmitted to other regions in a cooperative manner. It is shown that
      the effect of mutating hydrophobic residues is much greater than that observed
      upon mutation of a solvent-exposed polar residue.

PMID- 14567681
TI  - Drosophila TIMP is a potent inhibitor of MMPs and TACE: similarities in structure
      and function to TIMP-3.
AB  - The four tissue inhibitors of metalloproteinases (TIMPs) are endogenous
      inhibitors that regulate the activity of matrix metalloproteinases (MMPs) and
      certain disintegrin and metalloproteinase (ADAM) family proteases in mammals. The
      protease inhibitory activity is present in the N-terminal domains of TIMPs (N
      TIMPs). In this work, the N-terminal inhibitory domain of the only TIMP produced
      by Drosophila (dN-TIMP) was expressed in Escherichia coli and folded in vitro.
      The purified recombinant protein is a potent inhibitor of human MMPs, including
      membrane-type 1-MMP, although it lacks a disulfide bond that is conserved in all
      other known N-TIMPs. Titration with the catalytic domain of human MMP-3 [MMP
      3(DeltaC)] showed that dN-TIMP prepared by this method is correctly folded and
      fully active. dN-TIMP also inhibits, in vitro, the activity of the only two MMPs
      of Drosophila, dm1- and dm2-MMPs, indicating that the Drosophila TIMP is an
      endogenous inhibitor of the Drosophila MMPs. dN-TIMP resembles mammalian N-TIMP-3
      in strongly inhibiting human tumor necrosis factor-alpha-converting enzyme
      (TACE/ADAM17) but is a weak inhibitor of human ADAM10. Models of the structures
      of dN-TIMP and N-TIMP-3 are strikingly similar in surface charge distribution,
      which may explain their functional similarity. Although the gene duplication
      events that led to the evolutionary development of the four mammalian TIMPs might
      be expected to be associated with functional specialization, Timp-3 appears to
      have conserved most of the functions of the ancestral TIMP gene.

PMID- 14567682
TI  - Role of N-linked glycan in the unfolding pathway of Erythrina corallodendron
      lectin.
AB  - Erythrina corallodendron lectin (ECorL) exhibits an exquisitely structured
      oligosaccharide chain. Interestingly, the bacterially expressed, nonglycosylated
      counterpart, rECorL, possesses an essentially identical carbohydrate specificity
      and agglutinating activity as the glycosylated lectin, thus suggesting that the
      overall structure of the two are identical. This paper reports the unfolding
      behavior of E. corallodendron lectin in its glycosylated (EcorL) and
      nonglycosylated (rECorL) forms. ECorL shows a two-state unfolding pattern during
      isothermal melts and differential scanning calorimetry (DSC). The T(g) of ECorL
      as obtained from isothermal melts is 74 degrees C at pH 7.4. The T(p) obtained
      from DSC studies is between 74.8 to 68.1 degrees C in the pH range of 5.26-7.77.
      The recombinant lectin (rECorL), which is devoid of carbohydrate, shows, in
      contrast to the glycosylated protein, a non-two-state unfolding profile as
      measured by both probes mentioned, but the number of intermediates during
      unfolding could not be ascertained. Simulated annealing on ECorL, with the sugars
      removed, reveals that the protein Calpha backbones overlap, indicating that the
      overall structure, including the mode of dimerization, of rECorL is
      insignificantly altered as compared to ECorL. The alterations in the folding
      behavior of rECorL as compared to that observed in ECorL may be due to the fact
      that, unlike most other glycoproteins, one of the glycans in ECorL is unusually
      structured and forms many hydrogen bonds with the protein. It therefore appears
      that while the covalently linked sugar does not contribute appreciably to the
      final folded structure of ECorL, it does alter its folding process in a
      significant manner.

PMID- 14567683
TI  - Kinetic analysis of subunit oligomerization of the legume lectin soybean
      agglutinin.
AB  - The reconstitution of soybean agglutinin (SBA), a tetrameric GalNAc/Gal-specific
      legume lectin, after denaturation in urea has been studied using fluorescence,
      far-UV CD, a hemagglutination assay, and chemical cross-linking with
      glutaraldehyde as a bifunctional reagent. The reconstituted protein exhibits
      similar quaternary structure and activity as of native lectin. The kinetics of
      subunit oligomerization has been determined from the cross-linking reaction of
      the reconstituting protein followed by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE). Monomers and tetramers could be quantitatively
      analyzed during reconstitution. Dimers are not detectable. The reassociation
      reaction follows second-order kinetics. The results are described by a kinetic
      mechanism in which the monomer-to-dimer association (characterized by a second
      order rate constant (k(1)) of 1.4 x 10(4) M(-1) s(-1) at 37 degrees C) is
      involved in the rate-determining step of the oligomerization reaction.

PMID- 14567684
TI  - Circular dichroism and magnetic circular dichroism studies of the biferrous form
      of the R2 subunit of ribonucleotide reductase from mouse: comparison to the R2
      from Escherichia coli and other binuclear ferrous enzymes.
AB  - Ribonucleotide reductase (RNR) catalyzes the synthesis of the four
      deoxyribonucleotides needed for DNA synthesis and repair in living organisms. The
      reduced [Fe(II)Fe(II)] form of the model mammalian enzyme, mouse RNR R2, has been
      studied using a combination of circular dichroism (CD), magnetic circular
      dichroism (MCD), and variable-temperature variable-field (VTVH) MCD
      spectroscopies. Titrations of ferrous ion to the apo-enzyme have been performed
      and analyzed to investigate the metal binding affinity of the metal-binding site.
      Spectral features of individual iron sites have been analyzed to obtain detailed
      geometric and electronic structural information. VTVH MCD data have been
      collected and analyzed using two complementary models to obtain detailed ground
      state information including the zero-field splitting (ZFS) of both ferrous
      centers and the exchange coupling (J) between the two sites. These ground and
      excited state results provide a complete description of the biferrous site of
      mouse R2. The biferrous site consists of one 4- and one 5-coordinate iron, with
      positive and negative ZFS values, respectively. Weak exchange coupling between
      the two ferrous centers is present, consistent with having carboxylate bridges.
      The two sites have highly cooperative and weak metal binding affinities. This may
      be a novel regulatory mechanism for RNR. These results are compared with those
      from reduced Escherichia coli R2 and reduced acyl-carrier protein Delta(9)
      desaturase to correlate to similarities and differences in their dioxygen
      reactivity.

PMID- 14567685
TI  - Essential role of conserved arginine 160 in intramolecular electron transfer in
      human sulfite oxidase.
AB  - Arginine 160 in human sulfite oxidase (SO) is conserved in all SO species
      sequenced to date. Previous steady-state kinetic studies of the R160Q human SO
      mutant showed a remarkable decrease in k(cat)/K(m)(sulfite) of nearly 1000-fold,
      which suggests that Arg 160 in human SO makes an important contribution to the
      binding of sulfite near the molybdenum cofactor [Garrett, R. M., Johnson, J. L.,
      Graf, T. N., Feigenbaum, A., Rajagopalan, K. V. (1998) Proc. Natl. Acad. Sci.
      U.S.A. 95, 6394-6398]. In the crystal structure of chicken SO, Arg 138, the
      equivalent of Arg 160 in human SO, is involved in the formation of a positively
      charged sulfite binding site [Kisker, C., Schindelin, H., Pacheco, A., Wehbi, W.,
      Garnett, R. M., Rajagopalan, K. V., Enemark, J. H., Rees, D. C. (1997) Cell 91,
      973-983]. To further assess the role of Arg 160 in human SO, intramolecular
      electron transfer (IET) rates between the reduced heme [Fe(II)] and oxidized
      molybdenum [Mo(VI)] centers in the wild type, R160Q, and R160K human SO forms
      were investigated by laser flash photolysis. In the R160Q mutant, the IET rate
      constant at pH 6.0 was decreased by nearly 3 orders of magnitude relative to wild
      type, which indicates that the positive charge of Arg 160 is essential for
      efficient IET in human SO. Furthermore, the IET rate constant for the R160K
      mutant is about one-fourth that of the wild type enzyme, which strongly indicates
      that it is the loss of charge of Arg 160, and not its precise location, that is
      responsible for the much larger decrease in IET rates in the R160Q mutant. Steady
      state kinetic measurements indicate that IET is rate-limiting in the catalytic
      cycle of the R160Q mutant. Thus, the large decrease in the IET rate constant
      rationalizes the fatal impact of this mutation in patients with this genetic
      disorder.

PMID- 14567686
TI  - Tryptophan scanning mutagenesis in the alphaM3 transmembrane domain of the
      Torpedo californica acetylcholine receptor: functional and structural
      implications.
AB  - The functional role of the alphaM3 transmembrane domain of the Torpedo nicotinic
      acetylcholine receptor (AChR) was characterized by performing tryptophan-scanning
      mutagenesis at 13 positions within alphaM3, from residue M278 through I290. The
      expression of the mutants in Xenopus oocytes was measured by [(125)I]-alpha
      bungarotoxin binding, and ACh receptor function was evaluated by using a two
      electrode voltage clamp. Six mutants (L279W, F280W, I283W, V285W, S288W, and
      I289W) were expressed at lower levels than the wild type. Most of these residues
      have been proposed to face the interior of the protein. The I286W mutant was
      expressed at 2.4-fold higher levels than the wild type, and the two lipid-exposed
      mutations, F284W and S287W, were expressed at similar levels as wild type.
      Binding assays indicated that the alphaM3 domain can accommodate bulky groups in
      almost all positions. Three mutations, M282W, V285W, and I289W, caused a loss of
      receptor function, suggesting that the tryptophan side chains alter the
      conformational changes required for channel assembly or ion channel function.
      This loss of function suggests that these positions may be involved in helix
      helix contacts that are critical for channel gating. The lipid-exposed mutation
      F284W enhances the receptor macroscopic response at low ACh concentrations and
      decreases the EC(50). Taken together, our results suggest that alphaM3
      contributes to the gating machinery of the nicotinic ACh receptor and that
      alphaM3 is comprised of a mixture of two types of helical structures.

PMID- 14567687
TI  - Interaction of antimicrobial peptides with lipopolysaccharides.
AB  - We study the interaction of antimicrobial peptides with lipopolysaccharide (LPS)
      bilayers to understand how antimicrobial peptides interact with the LPS monolayer
      on the outer membrane of Gram-negative bacteria. LPS in water spontaneously forms
      a multilamellar structure composed of symmetric bilayers. We performed X-ray
      lamellar diffraction and wide-angle in-plane scattering to study the physical
      characteristics of LPS multilayers. The multilayer alignment of LPS is comparable
      to phospholipids. Thus, it is suitable for the application of oriented circular
      dichroism (OCD) to study the state of peptides in LPS bilayers. At high hydration
      levels, the chain melting temperature in multilamella detected by X-ray
      diffraction is the same as that of LPS aqueous dispersions, as measured by
      calorimetry. LPS has a strong CD, but with a careful subtraction of the lipid
      background, the OCD of peptides in LPS is measurable. The method was tested
      successfully with melittin. It was then applied to two representative
      antimicrobial peptides, magainin and protegrin. At peptide concentrations
      comparable to the physiological conditions, both peptides penetrate transmembrane
      in LPS bilayers. The results imply that antimicrobial peptides readily penetrate
      the LPS monolayer of the outer membrane.

PMID- 14567688
TI  - Mutation of the highly conserved tryptophan in the serpin breach region alters
      the inhibitory mechanism of plasminogen activator inhibitor-1.
AB  - We have demonstrated that interactions within the conserved serpin breach region
      play a direct role in the critical step of the serpin reaction in which the acyl
      enzyme intermediate must first be exposed to hydrolyzing water and aqueous
      deacylation. Substitution of the breach tryptophan in PAI-1 (Trp175), a residue
      found in virtually all known serpins, with phenylalanine altered the kinetics of
      the reaction mechanism and impeded the ability of PAI-1 to spontaneously become
      latent without compromising the inherent rate of cleaved loop insertion or
      partitioning between the final inhibited serpin-proteinase complex and hydrolyzed
      serpin. Kinetic dissection of the PAI-1 inhibitory mechanism using multiple
      target proteinases made possible the identification of a single rate-limiting
      intermediate step coupled to the molecular interactions within the breach region.
      This step involves the initial insertion of the proximal reactive center loop
      hinge residue(s) into beta-sheet A and facilitates translocation of the distal P'
      side of the cleaved reactive center loop from the substrate cleft of the
      proteinase. Substitution of the tryptophan residue raised the kinetic barrier
      restricting the initial loop insertion event, significantly retarding the rate
      limiting step in tPA reactions in which strong exosite interactions must be
      overcome for the reaction to proceed.

PMID- 14567689
TI  - Two rate-limiting steps in the kinetic mechanism of the serine/threonine specific
      protein kinase ERK2: a case of fast phosphorylation followed by fast product
      release.
AB  - Extracellular regulated protein kinase 2 (ERK2) is a eukaryotic protein kinase
      whose activity is regulated by mitogenic stimuli. To gain insight into the
      catalytic properties of ERK2 and to complement structure-function studies, we
      undertook a pre-steady state kinetic analysis of the enzyme. To do this, ERK2 was
      quantitatively activated by MAPKK1 in vitro by monitoring the stoichiometry and
      site specificity of phosphorylation using a combination of protein mass
      spectrometry, tryptic peptide analysis, and (32)P radiolabeling. Using a quench
      flow apparatus, MgATP(2-) was rapidly mixed (<1 ms) with both ERK2 and the
      protein substrate EtsDelta138 in the presence of a saturating total concentration
      (20 mM) of magnesium ion at 27 degrees C and pH 7.5. An exponential burst of
      product was observed over the first few milliseconds that followed mixing. This
      burst had an amplitude alpha of 0.44 and was followed by a slower linear phase.
      The pre-steady state burst is consistent with two partially rate-limiting
      enzymatic steps, which have the following rate constants: k(2) = 109 +/- 9 s(-1)
      and k(3) = 56 +/- 4 s(-1). These are attributed to rapid phosphorylation of
      EtsDelta138 and the process of product release, respectively. Single-turnover
      experiments provided an independent determination of k(2) (106 +/- 25 s(-1)). The
      observed catalytic constant (k(cat)(obs)) was found to be sensitive to the
      concentration of ERK2. The data fit a model in which ERK2 monomers form dimers
      and suggest that both the monomeric and dimeric forms of ERK2 are active with
      catalytic constants (k(cat)) of 25 and 37 s(-1), respectively. In addition, the
      model suggests that in the presence of saturating concentrations of both
      magnesium and substrates ERK2 subunits dissociate with a dissociation constant
      (K(d)) of 32 +/- 16 nM.

PMID- 14567690
TI  - Differences in the unfolding of procerain induced by pH, guanidine hydrochloride,
      urea, and temperature.
AB  - The structural and functional aspects along with equilibrium unfolding of
      procerain, a cysteine protease from Calotropis procera, were studied in solution.
      The energetic parameters and conformational stability of procerain in different
      states were also estimated and interpreted. Procerain belongs to the alpha + beta
      class of proteins. At pH 2.0, procerain exists in a partially unfolded state with
      characteristics of a molten globule-like state, and the protein is predominantly
      a beta-sheet conformation and exhibits strong ANS binding. GuHCl and temperature
      denaturation of procerain in the molten globule-like state is noncooperative,
      contrary to the cooperativity seen with the native protein, suggesting the
      presence of two parts in the molecular structure of procerain, possibly domains,
      with different stability that unfolds in steps. Moreover, tryptophan quenching
      studies suggested the exposure of aromatic residues to solvent in this state. At
      lower pH, procerain unfolds to the acid-unfolded state, and a further decrease in
      the pH drives the protein to the A state. The presence of 0.5 M salt in the
      solvent composition directs the transition to the A state while bypassing the
      acid-unfolded state. GuHCl-induced unfolding of procerain at pH 3.0 seen by
      various methods is cooperative, but the transitions are noncoincidental. Besides,
      a strong ANS binding to the protein is observed at low concentrations of GuHCl,
      indicating the presence of an intermediate in the unfolding pathway. On the other
      hand, even in the presence of urea (8 M), procerain retains all the activity as
      well as structural parameters at neutral pH. However, the protein is susceptible
      to unfolding by urea at lower pH, and the transitions are cooperative and
      coincidental. Further, the properties of the molten globule-like state and the
      intermediate state are different, but both states have the same conformational
      stability. This indicates that these intermediates may be located on parallel
      folding routes of procerain.

PMID- 14567691
TI  - An uncleavable procaspase-3 mutant has a lower catalytic efficiency but an active
      site similar to that of mature caspase-3.
AB  - We have examined the enzymatic activity of an uncleavable procaspase-3 mutant
      (D9A/D28A/D175A), which contains the wild-type catalytic residues in the active
      site. The results are compared to those for the mature caspase-3. Although at pH
      7.5 and 25 degrees C the K(m) values are similar, the catalytic efficiency
      (k(cat)) is approximately 130-fold lower in the zymogen. The mature caspase-3
      demonstrates a maximum activity at pH 7.4, whereas the maximum activity of
      procaspase-3 occurs at pH 8.3. The pK(a) values of both catalytic groups, H121
      and C163, are shifted to higher pH for procaspase-3. We developed limited
      proteolysis assays using trypsin and V8 proteases, and we show that these assays
      allow the examination of amino acids in three of five active site loops. In
      addition, we examined the fluorescence emission of the two tryptophanyl residues
      in the active site over the pH range of 2.5-9 as well as the response to several
      quenching agents. Overall, the data suggest that the major conformational change
      that occurs upon maturation results in formation of the loop bundle among loops
      L4, L2, and L2'. The pK(a) values of both catalytic groups decrease as a result
      of the loop movements. However, loop L3, which comprises the bulk of the
      substrate binding pocket, does not appear to be unraveled and solvent-exposed,
      even at lower pH.

PMID- 14567692
TI  - Mutations in the procaspase-3 dimer interface affect the activity of the zymogen.
AB  - The interface of the procaspase-3 dimer plays a critical role in zymogen
      maturation. We show that replacement of valine 266, the residue at the center of
      the procaspase-3 dimer interface, with glutamate resulted in an increase in
      enzyme activity of approximately 60-fold, representing a pseudoactivation of the
      procaspase. In contrast, substitution of V266 with histidine abolished the
      activity of the procaspase-3 as well as that of the mature caspase. While the
      mutations do not affect the dimeric properties of the procaspase, we show that
      the V266E mutation may affect the formation of a loop bundle that is important
      for stabilizing the active site. In contrast, the V266H mutation affects the
      positioning of loop L3, the loop that forms the bulk of the substrate binding
      pocket. In some cases, the amino acids affected by the mutations are >20 A from
      the interface. Overall, the results demonstrate that the integrity of the dimer
      interface is important for maintaining the proper active site conformation.

PMID- 14567693
TI  - Direct extracellular interaction between carbonic anhydrase IV and the human NBC1
      sodium/bicarbonate co-transporter.
AB  - Sodium/bicarbonate co-transporters (NBC) are crucial in the regulation of
      intracellular pH (pH(i)) and HCO(3)(-) metabolism. Electrogenic NBC1 catalyzes
      HCO(3)(-) fluxes in mammalian kidney, pancreas, and heart cells. Carbonic
      anhydrase IV (CAIV), which is also present in these tissues, is
      glycosylphosphatidyl inositol-anchored to the outer surface of the plasma
      membrane where it catalyzes the hydration-dehydration of CO(2)/HCO(3)(-). The
      physical and functional interactions of CAIV and NBC1 were investigated. NBC1
      activity was measured by changes of pH(i) in NBC1-transfected HEK293 cells
      subjected to acid loads. Cotransfection of CAIV with NBC1 increased the rate of
      pH(i) recovery by 44 +/- 3%, as compared to NBC1-alone. In contrast, CAIV did not
      increase the functional activity of G767T-NBC1 (mutated on the fourth
      extracellular loop (EC4) of NBC1), and G767T-NBC1, unlike wild-type NBC1, did not
      interact with CAIV in glutathione-S-transferase pull-down assays. This indicates
      that G767 of NBC1 is directly involved in CAIV interaction. NBC1-mediated pH(i)
      recovery rate after acid load was inhibited by 40 +/- 7% when coexpressed with
      the inactive human CAII mutant, V143Y. V143Y CAII competes with endogenous CAII
      for interaction with NBC1 at the inner surface of the plasma membrane, which
      indicates that NBC1/CAII interaction is needed for full pH(i) recovery activity.
      We conclude that CAIV binds EC4 of NBC1, and this interaction is essential for
      full NBC1 activity. The tethering of CAII and CAIV close to the NBC1 HCO(3)(-)
      transport site maximizes the transmembrane HCO(3)(-) gradient local to NBC1 and
      thereby activates the transport rate.

PMID- 14567694
TI  - Iron release from transferrin, its C-lobe, and their complexes with transferrin
      receptor: presence of N-lobe accelerates release from C-lobe at endosomal pH.
AB  - Human transferrin, like other members of the transferrin class of iron-binding
      proteins, is a bilobal structure, the product of duplication and fusion of an
      ancestral gene during the course of biochemical evolution. Although the two lobes
      exhibit 45% sequence identity and identical ligand structures of their iron
      binding sites (one in each lobe), they differ in their iron-binding properties
      and their responsiveness to complex formation with the transferrin receptor. A
      variety of interlobe interactions modulating these iron-binding functions has
      been described. We have now studied the kinetics of iron release to pyrophosphate
      from the isolated recombinant C-lobe and from that lobe in the intact protein,
      each free and bound to receptor. The striking finding is that the rates of iron
      release at the pH of the endosome to which transferrin is internalized by the
      iron-dependent cell are similar in the free proteins but 18 times faster from
      full-length monoferric transferrin selectively loaded with iron in the C-lobe
      than from isolated C-lobe when each is complexed to the receptor. The possibility
      that the faster release in the receptor complex of the full-length protein at
      endosomal pH contributes to the evolutionary advantage of the bilobal structure
      is considered.

PMID- 14567695
TI  - Kinetics of fibrinopeptide release by thrombin as a function of CaCl2
      concentration: different susceptibility of FPA and FPB and evidence for a
      fibrinogen isoform-specific effect at physiological Ca2+ concentration.
AB  - The kinetics of release of fibrinopeptide A (FPA) and B (FPB) by thrombin were
      investigated on unfractionated fibrinogen samples as a function of CaCl(2)
      concentration. A 50 mM Tris, 104 mM NaCl, pH 7.4 (TBS) buffer, to which 1 mM EDTA
      Na(2) (TBE) or 2.5 (TBC2.5), 14 (TBC14), and 30 mM CaCl(2) (TBC30) was
      alternatively added, was employed. The % FPA versus time curves were fitted with
      single stretched-exponential growth functions, where the stretch parameter beta
      likely reflects substrate polydispersity (beta = 1, monodisperse). For TBE, TBS,
      TBC14, and TBC30, we found beta approximately 1, with corresponding normalized
      rate constants (K(a)) of 3.8, 4.2, 2.7, and 1.9 x 10(-5) [(NIHu/L)s](-1).
      Surprisingly, in TBC2.5 we found beta = 0.69, with an "average" K(a) of 3.5 x 10(
      5) [(NIHu/L)s](-1). This effect disappeared [beta = 0.97, K(a) = 2.7 x 10(-5)
      [(NIHu/L)s](-1)] with an increase in the ionic strength I to that of TBC30 with
      186 mM NaCl (TBCaNa buffer). FPB releases were instead consistent with a
      nonstretched consecutive exponential growth function, except in TBC30 where some
      FPB appeared to be cleaved independently. Log-log plots of K(a) versus Ca(2+)
      concentration, Cl(-) concentration, or I showed a strong linear correlation with
      only the latter two except in TBCaNa, again suggesting specific effects of the
      physiological Ca(2+) concentration and I on FPA release. The corresponding K(b)
      plots showed instead that both total depletion and high Ca(2+) hampered FPB
      release. To further investigate the TBC2.5 beta = 0.69 effect, FG polydispersity
      was assessed by Western blot analyses. The thrombin-binding gamma'-chain isoform
      was approximately 4%, resulting in a bound:free thrombin ratio of approximately
      25:75. With regard to the C-terminal ends of the Aalpha-chains, approximately 45%
      were either intact or lightly degraded, while the remaining approximately 55%
      were more degraded. Fitting the % FPA release data in TBC2.5 with a sum of two
      exponentials resulted in a faster component and a slower component (K(a1)/K(a2)
      approximately 6), with a ratio of approximately 48:52. While a role for the
      gamma'-chain isoform cannot be excluded, this good correlation with the C
      terminal degradation of the Aalpha-chains suggests their calcium-dependent
      involvement in FPA release.

PMID- 14567697
TI  - Channel-opening kinetics of GluR2Q(flip) AMPA receptor: a laser-pulse photolysis
      study.
AB  - AMPA receptors mediate fast excitatory neurotransmission in the central nervous
      system. GluR2 is an AMPA receptor subunit that controls some key heteromeric AMPA
      receptor properties, such as calcium permeability. The kinetic properties of
      GluR2, relevant to the time scale of its channel opening, however, are poorly
      understood. Here, to measure the channel-opening kinetics, we use a laser-pulse
      photolysis technique, which permits glutamate to be liberated photolytically from
      gamma-O-(alpha-carboxy-2-nitrobenzyl)glutamate (caged glutamate) with a time
      constant of approximately 30 micros. We show that GluR2Q(flip), an unedited and
      Ca(2+) permeable isoform, is by far the fastest ligand-gated channel with the
      channel-opening and -closing rate constants being (8.0 +/- 0.49) x 10(4) and (2.6
      +/- 0.20) x 10(3) s(-1), respectively. Therefore, the shortest rise time (20-80%
      of the receptor current response) or the fastest observed time by which the
      GluR2Q(flip) channel can open is predicted to be 17 micros. The minimal kinetic
      mechanism for the channel opening is further consistent with the binding of two
      glutamate molecules with the channel-opening probability of 0.96. These results
      suggest that GluR2 is a temporally, highly efficient receptor to transduce the
      binding of chemical signals (i.e., glutamate) into an electrical impulse.

PMID- 14567696
TI  - A mutation causing a reduced level of expression of six beta4
      galactosyltransferase genes is the basis of the Lec19 CHO glycosylation mutant.
AB  - To identify factors required for the synthesis of complex glycans, we have
      isolated Chinese hamster ovary (CHO) cell mutants resistant to plant lectins. We
      previously identified Lec19 CHO cells as resistant to the Gal-binding lectins
      ricin, abrin, and modeccin and hypersensitive to the toxicity of other lectins
      that bind Gal, including L-PHA and E-PHA. Here we show that Lec19 cell extracts
      have a decreased ability to transfer Gal to simple sugar, oligosaccharide, and
      glycopeptide acceptors, particularly to biantennary, GlcNAc-terminated acceptors.
      Ricin(II)-agarose lectin affinity chromatography, oligomapping, and
      monosaccharide analyses provided evidence that Lec19 N-glycans have fewer Gal
      residues than CHO N-glycans. MALDI-TOF mass spectra of N-glycans released from
      Lec19 cell glycoproteins by peptide N-glycanase F revealed species with the
      predicted masses of neutral N-glycans with few Gal residues. Such truncated
      species are essentially absent from CHO cell glycoproteins. However, the
      complement of fully galactosylated or sialylated bi-, tri-, and tetra-antennary N
      glycans was largely equivalent in Lec19 and CHO cells. In addition, the coding
      region sequences of the beta4GalT-1, -T-2, -T-3, -T-4, -T-5, and -T-6 genes were
      identical in CHO and Lec19 cells. However, Northern analyses revealed an
      approximately 2-4-fold reduction in the level of transcripts of all six beta4GalT
      genes in Lec19 cells. Since the recessive Lec19 phenotype is the result of a loss
      of-function mutation, the combined data predict the existence of a trans-acting
      regulator of the steady-state level of transcripts that derive from these six
      mammalian beta4GalT genes.

PMID- 14567698
TI  - Channel-opening kinetics of GluR6 kainate receptor.
AB  - GluR6 is an ionotropic glutamate receptor subunit of the kainate subtype. It
      plays an essential role in synaptic plasticity and epilepsy. We expressed this
      recombinant receptor in HEK-293 cells and characterized the glutamate-induced
      channel-opening reaction, using a laser-pulse photolysis technique with the caged
      glutamate (gamma-O-(alpha-carboxy-2-nitrobenzyl)glutamate). This technique
      permits glutamate to be liberated photolytically from the caged glutamate with a
      time constant of approximately 30 micros. Prior to laser photolysis, the caged
      glutamate did not activate the GluR6 channel, nor did it inhibit or potentiate
      the glutamate response. At the transmembrane voltage of -60 mV, pH 7.4 and 22
      degrees C, the channel-opening and -closing rate constants were determined to be
      (1.1 +/- 0. 4) x 10(4) and (4.2 +/- 0.2) x 10(2) s(-1), respectively. The
      intrinsic dissociation constant of glutamate and the channel-opening probability
      were found to be 450 +/- 200 microM and 0.96, respectively. These constants are
      derived from a minimal kinetic mechanism of the channel activation involving the
      binding of two glutamate molecules. This mechanism describes the time course of
      the open-channel form of the receptor as a function of glutamate concentration.
      On the basis of the channel-opening rate constants obtained, the shortest rise
      time (20-80% of the receptor current response) or the fastest time by which the
      GluR6Q channel can open is predicted to be 120 micros. The open-channel form of
      the receptor determines the transmembrane voltage change, which in turn controls
      synaptic signal transmission between two neurons. The comparison of the channel
      opening kinetic rate constants between GluR6Q and GluR2Q(flip), reported in the
      companion paper, suggests that at a glutamate concentration of 100 microM, for
      instance, the integrated neuronal signal will be dominated by a slower GluR6Q
      receptor response, as compared to the GluR2Q(flip) component.

PMID- 14567699
TI  - Exclusion of a transmembrane-type peptide from ordered-lipid domains (rafts)
      detected by fluorescence quenching: extension of quenching analysis to account
      for the effects of domain size and domain boundaries.
AB  - Sphingolipid/cholesterol-rich rafts are membrane domains thought to exist in the
      liquid-ordered state. To understand the rules governing the association of
      proteins with rafts, the behavior of a model membrane-inserted hydrophobic
      polypeptide (LW peptide, acetyl-K(2)W(2)L(8)AL(8)W(2)K(2)-amide) was examined.
      The distribution of LW peptide between coexisting ordered and disordered lipid
      domains was probed by measuring the amount of LW Trp fluorescence quenched by a
      nitroxide-labeled phospholipid that concentrated in disordered lipid domains.
      Strong quenching of the Trp fluorescence (relative to quenching in model
      membranes lacking domains) showed that LW peptide was concentrated in quencher
      rich disordered domains and was largely excluded from ordered domains. Exclusion
      of LW peptide from the ordered domains was observed both in the absence and in
      the presence of 25-33 mol % cholesterol, indicating that the peptide is
      relatively excluded both from gel-state domains (which form in the absence of
      cholesterol) and from liquid-ordered-state domains (which form at high
      cholesterol concentrations). Because exclusion was also observed when ordered
      domains contained sphingomyelin in place of DPPC, or ergosterol in place of
      cholesterol, it appeared that this behavior was not strongly dependent on lipid
      structure. In both the absence and the presence of 25 mol % cholesterol,
      exclusion was also not strongly dependent upon the fraction of the bilayer in the
      form of ordered domains. To evaluate LW peptide behavior in more detail, an
      analysis of the effects of domain size and edges upon quenching was formulated.
      This analysis showed that quenching can be affected both by domain size and by
      whether a fluorescent molecule localized at domain edges. Its application to the
      quenching of LW peptide indicated that the peptide did not preferentially reside
      at the boundaries between ordered and disordered domains.

PMID- 14567700
TI  - Electrochemical and FTIR spectroscopic characterization of the cytochrome bc1
      complex from Paracoccus denitrificans: evidence for protonation reactions coupled
      to quinone binding.
AB  - The cytochrome bc(1) complex from Paracoccus denitrificans and soluble fragments
      of its cytochrome c(1) and Rieske ISP subunits are characterized by a combined
      approach of protein electrochemistry and FTIR difference spectroscopy. The FTIR
      difference spectra provide information about alterations in the protein upon
      redox reactions: signals from the polypeptide backbone, from the cofactors, and
      from amino acid side chains. We describe typical modes for conformational changes
      in the polypeptide and contributions of different secondary structure elements.
      Signals attributed to the different cofactors can be presented on the basis of
      selected potential steps. Modes associated with bound quinone are identified by
      comparison with spectra of quinone in solution at 1656, 1642, and 1610 cm(-1) and
      between 1494 and 1388 cm(-1), as well as at 1288 and 1262 cm(-1). Signals
      originating from the quinone bound at the Q(o) site can be distinguished. On the
      basis of the infrared data, the total quinone concentration is determined to be
      2.6-3.3 quinones per monomer, depending on preparation conditions. The balance of
      evidence supports the double-occupancy model. Interestingly, the amplitude of the
      band at 1746 cm(-1) increases with quinone content, reflecting a protonation
      reaction of acidic groups. In this context, the involvement of glutamates and/or
      aspartates in the vicinity of the Q(o) site is discussed on the basis of recently
      determined crystal structures.

PMID- 14567701
TI  - Reduction potentials of Rieske clusters: importance of the coupling between
      oxidation state and histidine protonation state.
AB  - Rieske [2Fe-2S] clusters can be classified into two groups, depending on their
      reduction potentials. Typical high-potential Rieske proteins have pH-dependent
      reduction potentials between +350 and +150 mV at pH 7, and low-potential Rieske
      proteins have pH-independent potentials of around -150 mV at pH 7. The pH
      dependence of the former group is attributed to coupled deprotonation of the two
      histidine ligands. Protein-film voltammetry has been used to compare three Rieske
      proteins: the high-potential Rieske proteins from Rhodobacter sphaeroides (RsRp)
      and Thermus thermophilus (TtRp) and the low-potential Rieske ferredoxin from
      Burkholderia sp. strain LB400 (BphF). RsRp and TtRp differ because there is a
      cluster to serine hydrogen bond in RsRp, which raises its potential by 140 mV.
      BphF lacks five hydrogen bonds to the cluster and an adjacent disulfide bond.
      Voltammetry measurements between pH 3 and 14 reveal that all the proteins,
      including BphF, have pH-dependent reduction potentials with remarkably similar
      overall profiles. Relative to RsRp and TtRp, the potential versus pH curve of
      BphF is shifted to lower potential and higher pH, and the pK(a) values of the
      histidine ligands of the oxidized and reduced cluster are closer together.
      Therefore, in addition to simple electrostatic effects on E and pK(a), the
      reduction potentials of Rieske clusters are determined by the degree of coupling
      between cluster oxidation state and histidine protonation state. Implications for
      the mechanism of quinol oxidation at the Q(O) site of the cytochrome bc(1) and
      b(6)f complexes are discussed.

PMID- 14567702
TI  - Poly(ADP-ribose) polymerase-1 dimerizes at a 5' recessed DNA end in vitro: a
      fluorescence study.
AB  - Activation of poly(ADP-ribose) polymerase-1 (PARP-1) is an immediate cellular
      reaction to DNA strand breakage as induced by alkylating agents, ionizing
      radiation, or oxidants. The resulting formation of protein-bound poly(ADP-ribose)
      facilitates survival of proliferating cells under conditions of DNA damage
      probably via its contribution to DNA base excision repair. In this study, we
      investigated the association of the amino-terminal DNA binding domain of human
      PARP-1 (hPARP-1 DBD) with a 5' recessed oligonucleotide mimicking a telomeric DNA
      end. We used the fluorescence of the Trp residues naturally occurring in the zinc
      finger domain of hPARP-1 DBD. Fluorescence intensity and fluorescence anisotropy
      measurements consistently show that the binding stoichiometry is two proteins per
      DNA molecule. hPARP-1 was found to bind the 5' recessed DNA end with a binding
      constant of approximately 10(14) M(-2) if a cooperative binding model is assumed.
      These results indicate that hPARP-1 DBD dimerizes during binding to the DNA
      target site. A footprint experiment shows that hPARP-1 DBD is asymmetrically
      positioned at the junction between the double-stranded and the single-stranded
      telomeric repeat. The largest contribution to the stability of the complex is
      given by nonionic interactions. Moreover, time-resolved fluorescence measurements
      are in line with the involvement of one Trp residue in the stacking interaction
      with DNA bases. Taken together, our data open new perspectives for interpretation
      of the selective binding of hPARP-1 to the junction between double- and single
      stranded DNA.

PMID- 14567703
TI  - Human alkyladenine DNA glycosylase uses acid-base catalysis for selective
      excision of damaged purines.
AB  - Human alkyladenine DNA glycosylase (AAG) protects against alkylative and
      oxidative DNA damage, flipping damaged nucleotides out of double-stranded DNA and
      catalyzing the hydrolytic cleavage of the N-glycosidic bond to release the
      damaged nucleobase. The crystal structure of AAG bound to a DNA substrate reveals
      features of the active site that could discriminate between oxidatively damaged
      or alkylated purines and normal purines. A water molecule bound in the active
      site adjacent to the anomeric carbon of the N-glycosidic bond is suggestive of
      direct attack by water, with Glu125 acting as a general base. However,
      biochemical evidence for this proposed mechanism has been lacking. The structure
      also fails to explain why smaller pyrimidine nucleosides are excluded as
      substrates from this relatively permissive active site that catalyzes the
      excision of a structurally diverse group of damaged purine bases. We have used pH
      dependencies, site-directed mutagenesis, and a variety of substrates to
      investigate the catalytic mechanism of AAG. Single-turnover excision of
      hypoxanthine and 1,N(6)-ethenoadenine follows bell-shaped pH-rate profiles,
      indicating that AAG-catalyzed excision of these neutral lesions requires the
      action of both a general acid and a general base. In contrast, the pH-rate
      profile for the reaction of 7-methylguanine, a positively charged substrate,
      shows only a single ionization corresponding to a general base. These results
      suggest that AAG activates neutral lesions by protonation of the nucleobase
      leaving group. Glu125 must be deprotonated in the active form of the enzyme,
      consistent with a role as a general base that activates and positions a water
      nucleophile. Acid-base catalysis can account for much of the 10(8)-fold rate
      enhancement that is achieved by AAG in the excision of hypoxanthine. The
      prominent role of nucleobase protonation in catalysis by AAG provides a rationale
      for its specialization toward damaged purines while effectively excluding
      pyrimidines.

PMID- 14567705
TI  - Close encounters of the transient kind: protein interactions in the
      photosynthetic redox chain investigated by NMR spectroscopy.
AB  - Plastocyanin and cytochrome c(6) function as electron shuttles between cytochrome
      f and photosystem I in the photosynthetic redox chain. To transfer electrons the
      partners form transient complexes, which are remarkably short-lived (milliseconds
      or less). Recent nuclear magnetic resonance studies have revealed details of the
      molecular interfaces found in such complexes. General features include a small
      binding site with a hydrophobic core and a polar periphery, including some
      charged residues. Furthermore, it was found that the interactions are relatively
      nonspecific. The structural information, in combination with kinetic and
      theoretical analyses of protein complexes, provides new insight into the nature
      of transient protein interactions.

PMID- 14567704
TI  - Biosynthesis of the thiazole moiety of thiamin pyrophosphate (vitamin B1).
AB  - While most of the proteins required for the biosynthesis of thiamin pyrophosphate
      have been known for more than a decade, the reconstitution of this biosynthesis
      in a defined biochemical system has been difficult due to the novelty of the
      chemistry involved. Here we demonstrate the first successful enzymatic synthesis
      of the thiazole moiety of thiamin from glycine, cysteine, and deoxy-D-xylulose-5
      phosphate using overexpressed Bacillus subtilis ThiF, ThiS, ThiO, ThiG, and a
      NifS-like protein. This has facilitated the identification of the biochemical
      function of each of the proteins involved: ThiF catalyzes the adenylation of
      ThiS; NifS catalyzes the transfer of sulfur from cysteine to the acyl adenylate
      of ThiS; ThiO catalyzes the oxidation of glycine to the corresponding imine; and
      ThiG catalyzes the formation of the thiazole phosphate ring. The complex
      oxidative cyclization reaction involved in the biosynthesis of the thiamin
      thiazole has been greatly simplified by replacing ThiF, ThiS, ThiO, and NifS with
      defined biosynthetic intermediates in a reaction where ThiG is the only required
      enzyme.

PMID- 14567706
TI  - Palladium-catalyzed coupling of sp(2)-hybridized tellurides.
AB  - Vinylic tellurides are of importance due to their useful behavior as synthons and
      intermediates. Recently, the use of these compounds in place of vinylic halides
      or triflates in the palladium-catalyzed cross-coupling reaction has emerged as a
      powerful tool in the preparation of conjugated enyne and enediyne. In this way,
      vinylic tellurides can behave as aryl or vinyl carbocation equivalents. This
      review focuses on methods that involve the use of vinylic tellurides in palladium
      catalyzed cross coupling reaction.

PMID- 14567708
TI  - A conversation on VB vs MO theory: a never-ending rivalry?
AB  - Quantum mechanics has provided chemistry with two general theories, valence bond
      (VB) theory and molecular orbital (MO) theory. The two theories were developed at
      about the same time, but quickly diverged into rival schools that have competed,
      sometimes fervently, on charting the mental map and epistemology of chemistry.
      Three practitioners of MO and VB theory talk - fighting a little, trying to
      understand - of the past and present of these two approaches to describing
      bonding in molecules.

PMID- 14567707
TI  - Titanium-catalyzed enantioselective additions of alkyl groups to aldehydes:
      mechanistic studies and new concepts in asymmetric catalysis.
AB  - The catalytic asymmetric addition of alkyl groups to aldehydes is an important
      reaction in the enantioselective synthesis of secondary alcohols. This reaction
      can be catalyzed by zinc- or titanium-based catalysts. While the mechanism of the
      zinc/amino alcohol catalysts has received significant attention, the titanium
      based catalysts have been less studied. This Account summarizes our mechanistic
      studies with bis(sulfonamide) and BINOL-derived titanium catalysts. It also
      describes our use of this reaction in the development of new approaches to
      asymmetric catalysis, including applications of diastereomeric catalysts and
      optimization of asymmetric catalysts with achiral and meso ligands.

PMID- 14567709
TI  - Avoiding the road less traveled: how the topology of enzyme-substrate complexes
      can dictate product selection.
AB  - Enzymes are remarkable not only in their ability to enhance reaction rates, but
      also because they do so selectively, directing reactive intermediates toward only
      one of multiple potential products. 1-Aminocyclopropane-1-carboxylate (ACC)
      synthase and 7,8-diaminopelargonic acid synthase are pyridoxal 5'-phosphate
      dependent enzymes that utilize S-adenosyl-l-methionine as a substrate but yield
      different products. The former produces ACC by alpha,gamma-elimination, while the
      latter makes S-adenosyl-4-methylthio-2-oxobutanoate by transamination. The
      mechanisms of these two reactions are the same up to the formation of a quinonoid
      intermediate, from which they diverge. This Account explores how the active-site
      topology of the enzyme-intermediate complexes decides this pathway bifurcation.

PMID- 14567710
TI  - Stereoselective synthesis of polypropionate units and heterocyclic compounds by
      cyclopropylcarbinol ring-opening with mercury(II) salts.
AB  - The mercury(II)-mediated electrophilic ring-opening reaction of various
      cyclopropylcarbinol derivatives bearing adjacent stereocenters and a remote
      nucleophilic functional group provides a useful strategy for synthesizing
      compounds bearing several contiguous stereocenters. These highly
      diastereoselective reactions occur with anchimeric assistance by the internal
      nucleophilic moiety and afford synthetically valuable building blocks such as
      polypropionate units or heterocyclic compounds. The application of
      cyclopropylcarbinol ring-opening for the preparation of functionalized oxygen
      heterocycles in natural product synthesis is also outlined.

PMID- 14567711
TI  - The emergence of allenamides in organic synthesis.
AB  - This Account highlights recent studies describing utility of allenamides in
      stereoselective inter- and intramolecular synthetic methodologies. It is written
      to raise interest in the chemistry of allenamides.

PMID- 14567712
TI  - PARACEST agents: modulating MRI contrast via water proton exchange.
AB  - Scientific interest in optimizing the properties of gadolinium (III) complexes as
      MRI contrast agents has led to many new insights into lanthanide ion coordination
      chemistry in the last two decades. Among these was the surprising observation
      that water exchange in lanthanide (III) derivatives of DOTA can be modulated
      dramatically by judicious choice of ligand side chain and Ln(3+) ionic radii.
      This resulted in the discovery of paramagnetic CEST agents for altering MRI image
      contrast based upon the chemical exchange saturation transfer mechanism. The goal
      of this article is to review the factors that govern water molecule and water
      proton exchange in these complexes and to compare the potential sensitivity of
      PARACEST agents versus Gd(3+)-based T(1) relaxation agents for altering tissue
      contrast.

PMID- 14567713
TI  - Multiple transient response methods to identify mechanisms of heterogeneous
      catalytic reactions.
AB  - Identification of mechanisms of heterogeneous catalytic reactions is challenging
      because there are few effective in-situ techniques with which to determine
      reactive intermediates on surfaces. An effective multiple transient technique
      consisting of a combination of a broadened pulse with step changes and a sharp
      isotopic pulse was developed in our group. This technique provides much richer
      dynamic information than is obtainable from experiments with individual pulses or
      step changes in reactant concentration. In this Account, we illustrate the method
      by its application to high-temperature heterogeneous catalytic reactions.

PMID- 14567714
TI  - Electron transfer between membrane complexes and soluble proteins in
      photosynthesis.
AB  - Photosynthesis consists of a series of endergonic redox reactions, with light as
      the source of energy, chlorophyll as the energy converter, and electrons flowing
      through membrane and soluble proteins. Here, we give an account of the most
      recent results on the structure-function relationships of the membrane-embedded
      complexes cytochrome b(6)-f and photosystem I and of the two soluble proteins
      (cytochrome c(6) and plastocyanin) that serve as alternative electron carriers
      between them. Particular attention is paid to the evolutionary aspects of the
      reaction mechanism and transient protein-protein interactions between the
      membrane complexes and their partners in cyanobacteria, eukaryotic algae, and
      plants.

PMID- 14567715
TI  - A descriptive analysis of internet information regarding music therapy.
AB  - The purpose of the two studies reported here was to investigate and describe
      information available about music therapy that is likely to be found on the
      Internet. The top 20 Internet search engines were surveyed using the term "Music
      Therapy." Information concerning the first 25 sites listed per engine was
      collected. The following categories of information were described: the frequency
      of mention across the search engine sites, the type of site, whether the site
      gave a definition of music therapy, the orientation of that definition, the
      number of links, orientation of links, and the number of hits shown on the main
      page. A rank order was then compiled of the 267 sites listed across all searches.
      Results showed that American Music Therapy Association (AMTA) web page was the
      most frequent and highest ranked site across the 20 search engine sites. Sites
      from educational institutions were frequent, as were commercial sites. Most of
      the highest ranked sites gave traditional definitions (as defined by AMTA) for
      music therapy and associated links were conventional as well. These procedures
      were replicated one year later, although the question "What is Music Therapy?"
      was used as the search term. Results from this second search revealed only 145
      sites. Of those, American Music Therapy Association web page was again the most
      frequent and highest ranked site across the search engines. Sites from
      educational institutions were frequent, as were commercial sites, however, only
      half of the highest ranked sites gave traditional definitions for music therapy.

PMID- 14567716
TI  - Ramipril-associated hepatotoxicity.
AB  - CONTEXT: Angiotensin-converting enzyme inhibitors are prescribed for many
      cardiovascular and renal diseases. Adverse hepatic events, especially
      cholestasis, have rarely been reported with captopril, enalapril, lisinopril, and
      fosinopril. To date, hepatic injury associated with ramipril has not been
      reported. OBJECTIVE: To describe 3 patients who developed hepatitis, with or
      without jaundice, after receiving ramipril. DESIGN: Medical records and liver
      biopsies of the 3 patients were reviewed. Clinical, laboratory, and histologic
      findings were compared with findings in other cases of angiotensin-converting
      enzyme inhibitor-induced liver injury reported in the literature. RESULTS: The 3
      patients were middle-aged men. In 2 patients, jaundice appeared 4 and 8 weeks
      after starting ramipril. Bilirubin levels peaked at 15.5 and 5 mg/dL, and
      alkaline phosphatase values peaked at 957 and 507 U/L. Aminotransferase levels
      were mildly elevated. Endoscopic retrograde cholangiopancreatography and
      ultrasonography showed no bile duct obstruction. Liver biopsies from the
      jaundiced patients were similar, with cholestasis, duct necrosis, and
      extravasation of bile, ductular proliferation, and portal inflammation.
      Cholestasis improved in 1 patient 6 weeks after stopping ramipril and was
      prolonged for 14 months in the other, in whom biliary cirrhosis was present on
      biopsy. The third patient developed hepatitis without jaundice 3 weeks after
      starting ramipril; symptoms resolved after stopping the drug. Ramipril-associated
      liver injury is similar to that seen with other angiotensin-converting enzyme
      inhibitors, but liver biopsy findings of duct necrosis and extravasation of bile
      have not been reported previously. CONCLUSION: Prolonged cholestatic hepatitis
      and biliary cirrhosis may result from the use of ramipril. Monitoring of liver
      enzymes is advisable for patients starting on ramipril.

PMID- 14567717
TI  - Interpretation of skin biopsies by general pathologists: diagnostic discrepancy
      rate measured by blinded review.
AB  - CONTEXT: Slide review has been advocated as a means to reduce diagnostic error in
      surgical pathology and is considered an important component of a total quality
      assurance program. Blinded review is an unbiased method of error detection, and
      this approach may be used to determine the diagnostic discrepancy rates in
      surgical pathology. OBJECTIVE: To determine the diagnostic discrepancy rate for
      skin biopsies reported by general pathologists. DESIGN: Five hundred eighty-nine
      biopsies from 500 consecutive cases submitted by primary care physicians and
      reported by general pathologists were examined by rapid-screen, blinded review by
      2 dermatopathologists, and the original diagnosis was compared with the review
      interpretation. RESULTS: Agreement was observed in 551 (93.5%) of 589 biopsies.
      Blinded review of these skin biopsies by experienced dermatopathologists had a
      sensitivity of 100% (all lesions originally reported were detected during
      review). False-negative errors were the most common discrepancy, but false
      positives, threshold discrepancies, and differences in type or grade were also
      observed. Only 1.4% of biopsies had discrepancies that were of potential clinical
      importance. CONCLUSIONS: Blinded review demonstrates that general pathologists
      reporting skin biopsies submitted by primary care physicians have a low
      diagnostic error rate. The method detects both false-negative and false-positive
      cases and identifies problematic areas that may be targeted in continuing
      education activities. Blinded review is a useful component of a dermatopathology
      quality improvement program.

PMID- 14567718
TI  - Utility of Gram stain for the microbiological analysis of burn wound surfaces.
AB  - CONTEXT: Surface swab cultures have attracted attention as a potential
      alternative to biopsy histology or quantitative culture methods for
      microbiological burn wound monitoring. To our knowledge, the utility of adding a
      Gram-stained slide in this context has not been evaluated previously. OBJECTIVE:
      To determine the degree of correlation of Gram stain with culture for the
      microbiological analysis of burn wound surfaces. DESIGN: Prospective laboratory
      analysis. SETTING: Urban health region/centralized diagnostic microbiology
      laboratory. PATIENTS: Burn patients hospitalized in any Calgary Health Region
      burn center from November 2000 to September 2001. INTERVENTION: Gram stain plus
      culture of burn wound surface swab specimens obtained during routine dressing
      changes or based on clinical signs of infection. MAIN OUTCOME MEASURES: Degree of
      correlation (complete, high, partial, none), including weighted kappa statistic
      (kappa(w)), of Gram stain with culture based on quantitative microscopy and
      degree of culture growth. RESULTS: A total of 375 specimens from 50 burn patients
      were evaluated. Of these, 239 were negative by culture and Gram stain, 7 were
      positive by Gram stain only, 89 were positive by culture only, and 40 were
      positive by both methods. The degree of complete, high, partial, and no
      correlation of Gram stain with culture was 70.9% (266/375), 1.1% (4/375), 2.4%
      (9/375), and 25.6% (96/375), respectively. The degree of correlation for all 375
      specimens, as expressed by the weighted kappa statistic, was found to be fair
      (kappa(w) = 0.32).Conclusion.-The Gram stain is not suitable for the
      microbiological analysis of burn wound surfaces.

PMID- 14567719
TI  - Growth factors and receptors in juvenile nasopharyngeal angiofibroma and nasal
      polyps: an immunohistochemical study.
AB  - BACKGROUND: Juvenile nasopharyngeal angiofibroma is a rare nasopharyngeal tumor
      that occurs exclusively in adolescent boys. It is a histologically benign but
      locally persistent growth of stromal and vascular tissue. Although male hormones
      and some growth factors, such as transforming growth factor beta1 (TGF-beta1),
      insulin-like growth factor II (IGF-II), and, lately, the proto-oncogene beta
      catenin, have been implicated in the histogenesis of the tumor, the biologic
      signaling pathways that drive this peculiar fibrovascular proliferation are still
      nuclear. OBJECTIVE: To evaluate immunoexpressions of beta-catenin, c-Kit,
      p130Cas, TGF-beta3, bone morphogenic protein 4, nerve growth factor (NGF), and
      the IGF receptor (IGF-1R) in a series of juvenile nasopharyngeal angiofibromas
      and to compare to that of a group of nasal polyps. DESIGN: A standard
      immunohistochemical technique was used on paraffin sections of 12 sporadic
      juvenile nasopharyngeal angiofibromas and 15 nasal polyps with microwave or steam
      antigen retrieval. Immunoreactivity was analyzed semiquantitatively in stromal
      cells and endothelial cells of each case. RESULTS: The expressions of beta
      catenin (nuclear), c-Kit (cytoplasmic), and NGF (cytoplasmic) were higher and
      more frequent in stromal cells of juvenile nasopharyngeal angiofibromas than
      those of nasal polyps. Both juvenile nasopharyngeal angiofibromas and nasal
      polyps showed similarly frequent and strong immunoreactivity for p130Cas and TGF
      beta3 and weak immunoreactivity for bone morphogenic protein 4 in both stromal
      cells and endothelial cells. No IGF-1R immunoreactivity was detected in any case
      of either group. CONCLUSIONS: Our results support the role of beta-catenin in
      juvenile nasopharyngeal angiofibromas and suggest a potential involvement of c
      Kit and NGF signaling pathways in the juvenile nasopharyngeal angiofibromas.
      Although the biologic significance of c-Kit in juvenile nasopharyngeal
      angiofibromas has yet to be defined, the finding of frequent and high c-Kit
      expression might have therapeutic importance for patients with juvenile
      nasopharyngeal angiofibromas.

PMID- 14567720
TI  - Lipochoristomas (lipomatous tumors) of the acoustic nerve.
AB  - CONTEXT: Lipochoristomas (lipomatous choristomas) are rare tumors of the acoustic
      nerve (cranial nerve VIII/vestibulocochlear nerve) within the internal acoustic
      canal and sometimes the cerebellopontine angle, and are histogenetically believed
      to be congenital malformations. Their clinically indolent behavior has recently
      prompted a more conservative management protocol in a quest for maximal
      nerve/hearing preservation. This approach contrasts sharply with that for the
      common internal acoustic canal/cerebellopontine angle tumors, the neuroepithelial
      neoplasms (acoustic schwannomas and meningiomas), which behave more aggressively
      and have more prominent clinical manifestations. Owing to their rarity, the
      clinicopathologic features of cranial nerve VIII lipochoristomas have been
      obtained mainly through case reports. OBJECTIVE: We present the clinicopathologic
      features of 11 cases of lipochoristomas of cranial nerve VIII. DESIGN: The 11
      cases were documented between 1992 and 2003. We performed complete clinical
      reviews with histologic, histochemical, and immunohistochemical analyses of
      formalin-fixed, paraffin-embedded tumor samples. RESULTS: The patients were 8 men
      and 3 women with hearing loss of the right ear (5 patients) or the left ear (6
      patients). No patient had bilateral tumors. All lipochoristomas histologically
      possessed mature adipose tissue admixed with varied amounts of mature fibrous
      tissue, tortuous thick-walled vessels, smooth muscle bundles, and skeletal muscle
      fibers, the latter verified with immunohistochemistry. CONCLUSIONS: The
      histomorphologic and immunophenotypic evidence showed that these tumors are
      better characterized as choristomas than as simple "lipomas," as they have been
      labeled in the past. Their overall nonaggressive clinical nature in addition to
      the characteristic radiologic and histomorphologic findings are important
      clinicopathologic features for the pathologist to recognize and differentiate,
      especially during frozen section evaluations, in order to direct the neurosurgeon
      to a more appropriate conservative therapeutic intervention.

PMID- 14567721
TI  - Human papillomavirus infection of the epididymis and ductus deferens: an
      evaluation by nested polymerase chain reaction.
AB  - CONTEXT: Human papillomaviruses (HPVs) play an important role in the etiology of
      squamous cell carcinoma of the uterine cervix. The possible role of the male
      urogenital tract as a reservoir of HPV infection is not fully understood. We
      inferred from our previous observation of HPV-31 in epididymal tissue in a case
      of chronic epididymitis that HPV might be commonly present in cases of
      epididymitis caused by sexually transmitted pathogens. OBJECTIVE: To assess the
      presence of HPV in the epididymis and ductus deferens in nontuberculous
      epididymitis. DESIGN: Epididymal samples obtained from 17 patients and epididymal
      and ductus deferens samples from 5 patients surgically treated for nontuberculous
      epididymitis were analyzed by nested polymerase chain reaction for the presence
      of HPV DNA. In positive samples, the HPV type was determined by DNA sequencing.
      SETTING: Tertiary-care academic hospital and national reference laboratory for
      papillomaviruses. RESULTS: Low-risk HPV type 6 and high-risk HPV types 16, 33,
      35, 55, and 73 were detected in 7 patients (31%). Neither koilocytes nor
      dysplastic changes were found in the epididymis and ductus deferens. CONCLUSION:
      Low-risk and high-risk HPV types were detected in the epididymis and ductus
      deferens of patients with nontuberculous epididymitis. The infection was not
      accompanied by koilocytic atypia or dysplasia. Our findings support the
      hypothesis that the male urogenital tract serves as a reservoir of HPV infection.

PMID- 14567722
TI  - Autopsy findings in an outbreak of severe systemic illness in heroin users
      following injection site inflammation: an effect of Clostridium novyi exotoxin?
AB  - CONTEXT: An epidemic of unexplained illness among injecting drug users
      characterized by injection site inflammation and severe systemic toxicity
      occurred in Ireland and the United Kingdom from April to August 2000. One hundred
      eight persons became ill, and 43 persons died. In Dublin, 8 of 22 patients died.
      Six of the 8 fatal cases were epidemiologically linked to a source of heroin.
      Most had experienced local injection site lesions for 7 to 14 days before
      developing a rapidly fatal systemic illness characterized by hypotension, thirst,
      pulmonary edema, pericardial and pleural effusions, and leukocytosis. OBJECTIVE:
      To document the clinical course and autopsy findings of the fatal cases in
      Dublin. DESIGN: To study the clinical, autopsy, microbiologic, and toxicologic
      findings from the 8 fatal cases in Dublin. RESULTS: In Dublin, there were 6 men
      and 2 women who were fatally involved in the epidemic, with the mean age being 34
      years (range, 22-51 years). The injection site inflammations involved the buttock
      (n = 4), leg, iliac region, arm, and a Portacath site. At autopsy, the local
      lesions were ulcerated, swollen, and indurated but were inconspicuous in 2
      patients. All the deceased had pulmonary edema. There were pleural effusions in
      7, 2 of whom had pericardial effusions. Five had prominent left ventricular
      subendocardial hemorrhages. Five had splenomegaly. Microscopy showed pulmonary
      edema and a granulocytic reaction mainly in the spleen, marrow, and myocardium.
      Toxicology showed a range of narcotic drugs in the toxic or fatal range.
      Clostridium novyi type A, a fastidious toxin-producing anaerobe, was identified
      in 2 cases. CONCLUSION: The clinicopathologic findings of a local inflammatory
      lesion followed 7 to 14 days later by a rapidly fatal systemic illness are
      consistent with the effect of exotoxin produced by organisms growing in the local
      inflammatory site. Clostridium novyi-derived exotoxin is the likely cause of such
      a syndrome, although the fastidious organism was isolated from only 2 of 8 cases
      (from none of the 14 surviving patients and from only 13 of 60 cases in
      Scotland). In the setting of an epidemic, the toxic and fatal range blood levels
      of narcotics are unlikely to explain these events, and no other candidate
      organism could be isolated. The heroin is likely to have come from Afghanistan,
      but local contamination at a putative distribution site in the United Kingdom is
      more likely than international terrorism to be the initiating factor.

PMID- 14567724
TI  - Her-2/neu status in breast cancer metastases to the central nervous system.
AB  - CONTEXT: Breast cancer is lethal when it metastasizes; one frequent site for
      spread is the central nervous system (CNS). Approximately 15% to 30% of breast
      cancers overexpress the protein HER-2/neu at the primary site, but there are few
      data on whether metastases from these tumors overexpress HER-2/neu and might be
      responsive to the potentially toxic anti-HER-2/neu immunotherapy (trastuzumab
      [Herceptin]) used in patients with disseminated disease. OBJECTIVE: To assess CNS
      breast cancer metastases for HER-2/neu protein overexpression by
      immunohistochemistry and gene amplification by fluorescence in situ hybridization
      (FISH) and to compare the status in primary and metastatic sites in the same
      patient, whenever possible. DESIGN: Central nervous system breast cancer
      metastases (n = 53) from 33 patients and corresponding primary breast cancer
      specimens in a subset of these patients (n = 12) were retrospectively identified
      in surgical pathology and autopsy databases. Fluorescence in situ hybridization
      analysis using PathVysion probes for HER-2/neu and chromosome enumeration probe
      17 (CEP 17) and immunohistochemistry using the c-Erb-B2 antibody (Dako A0485)
      were compared. Immunohistochemical sections were evaluated by both visual and
      image analysis techniques. RESULTS: Of 31 cases assessable by FISH, 26% showed
      gene amplification. One hundred percent concordance for HER-2/neu status was
      detected between the primary and CNS metastatic lesions in 10 of 10 patients
      analyzed by FISH; lesser concordance was noted in 12 cases compared by
      immunohistochemistry. In 9 patients with multiple CNS metastases, FISH showed
      concordance among different lesions within the same patient. CONCLUSIONS: When
      FISH is the detection method, CNS metastases accurately reflect the HER-2/neu
      status of the primary tumor. Central nervous system metastases from breast cancer
      received as surgical specimens can therefore be used to assess HER-2/neu status
      in patients in whom the primary tumor is unavailable for analysis.

PMID- 14567723
TI  - Differential amplification and overexpression of HER-2/neu, p53, MIB1, and
      estrogen receptor/progesterone receptor among medullary carcinoma, atypical
      medullary carcinoma, and high-grade invasive ductal carcinoma of breast.
AB  - CONTEXT: Medullary carcinoma (MC) is a special type of breast cancer that has a
      better prognosis than atypical medullary carcinoma (AMC) and high-grade invasive
      ductal carcinoma (HGIDC) with prominent lymphocytic infiltrates. What accounts
      for the different clinical courses of these carcinomas, despite their similar
      histology, is unknown. To address this issue, we performed a comparative study of
      amplification and overexpression of HER-2/neu and expression of several other
      important biochemical markers (p53, MIB1, and estrogen receptor [ER]/progesterone
      receptor [PR]) in these 3 cancer groups. OBJECTIVE: To evaluate HER-2/neu, p53,
      MIB1, and ER/PR as markers in the differential diagnosis of MC, AMC, and
      HGIDC.Design.-Nine cases of MC, 13 cases of AMC, and 16 cases of HGIDC with
      prominent lymphocytic infiltrates were identified according to strict histologic
      criteria. All tests were performed on formalin-fixed, paraffin-embedded archival
      tissues. HER-2/neu gene amplification was examined by fluorescence in situ
      hybridization using PathVysion HER-2 DNA probes. Expression of HER-2/neu, p53,
      MIB1, and ER/PR was detected by immunohistochemistry. chi2 and Student t tests
      were applied for statistical analyses. RESULTS: None of 9 cases of MC examined
      had either amplification or overexpression of HER-2/neu (0%). In contrast, HER
      2/neu amplification was observed in AMC (46%, P <.025) and HGIDC (56%, P <.005).
      All 3 categories of tumors had similar percentages of expression of p53 (78% of
      MC, 77% of AMC, and 69% of HGIDC) and MIB1 (89% of MC, 92% of AMC, and 94% of
      HGIDC). Immunostaining for ER/PR was rarely positive in either MC or AMC, and
      there were no significant differences of expression of ER/PR between these 2
      lesions (P >.05). However, the expression rate of ER/PR (31%/44%) in HGIDC is
      higher than in both MC (P =.05) and AMC (P =.01). CONCLUSIONS: Medullary
      carcinoma of breast is distinct from AMC and HGIDC with prominent lymphocytic
      infiltrates in amplification and overexpression of HER-2/neu. This difference may
      account for its different clinical and biological behavior, and may potentially
      aid in diagnosis and management of these groups of patients.

PMID- 14567725
TI  - Comparative studies of somatic and ongoing mutations in immunoglobulin heavy
      chain variable region genes in diffuse large B-cell lymphomas of the stomach and
      the small intestine.
AB  - CONTEXT: Many diffuse large B-cell lymphomas (DLBCLs) of the stomach are believed
      to represent high-grade transformation of low-grade marginal zone B-cell lymphoma
      of mucosa-associated lymphoid tissue type, which is of memory B-cell origin,
      displaying evidence for positive antigen selection and a low level of ongoing
      somatic mutation of the rearranged immunoglobulin heavy-chain variable region
      (V(H)) genes. The pattern of somatic mutation has been studied little in
      intestinal DLBCLs. OBJECTIVE: To assess evidence for antigen selection and the
      levels of ongoing mutation, we analyzed the ratio of replacement to silent
      mutations, as well as the frequency of intraclonal sequence variation in gastric
      and small intestinal DLBCLs that showed no concomitant low-grade component.
      DESIGN: Genomic DNA was extracted from formalin-fixed paraffin blocks of gastric
      (n = 6) and small intestinal (n = 6) DLBCLs. The complementarity-determining
      region 2 and framework region 3 sequences (<200 base pairs) of the rearranged
      immunoglobulin V(H) gene were obtained from polymerase chain reaction-amplified
      product, and the ratio of replacement-to-silent mutations and the frequency of
      intraclonal sequence variation were determined. RESULTS: Clustering of
      replacement mutations in complementarity-determining region 2 with a high (>2.9)
      ratio of replacement-to-silent mutations was observed in 5 gastric DLBCLs,
      whereas it was recognized in only 1 intestinal DLBCL. Intraclonal sequence
      variation was observed in 6 intestinal and 5 gastric DLBCLs. The frequency of
      ongoing mutation was much higher in the intestinal (median, 0.33%) than in the
      gastric DLBCLs (median, 0.13%), but the difference was not statistically
      significant (P =.09). CONCLUSIONS: The mutation pattern was consistent with
      positive antigen selection in gastric DLBCLs, but not in the intestinal tumors.
      Ongoing mutation was much more frequent in the intestinal than in the gastric
      DLBCLs. These findings suggest that positive antigen selection plays a major role
      in a significant proportion of gastric tumors, whereas germinal center reaction
      with aberrant mutation is important in small intestinal DLBCLs.

PMID- 14567726
TI  - Intraoperative testing for parathyroid hormone: a comprehensive review of the use
      of the assay and the relevant literature.
AB  - OBJECTIVE: The rapid intraoperative parathyroid hormone assay is transforming the
      parathyroidectomy procedure. We present a review of the literature on the use of
      the assay as an adjunct to surgery. To our knowledge, this is the first review of
      the literature to encompass and compare all known primary studies of this assay
      in parathyroidectomy patients. DATA SOURCES: Articles were collected by searching
      MEDLINE databases using relevant terminology. The references of these articles
      were reviewed for additional studies. Supplementary articles pertinent to the
      parathyroidectomy procedure, preoperative parathyroid localization studies, and
      intraoperative parathyroid hormone assay development also were examined. STUDY
      SELECTION AND DATA EXTRACTION: One hundred sixty-five references were analyzed
      and categorized separately into groups. DATA SYNTHESIS: The primary studies of
      intraoperative data on patients undergoing parathyroidectomy were compared when
      possible. Studies were analyzed by type of assay used, where performed,
      turnaround time, and efficiency of use. Reviews of the types of parathyroid
      surgery and preoperative localization were included for educational
      purposes.Conclusions.-The intraoperative parathyroid hormone assay is a useful
      adjunct to preoperative imaging and parathyroid surgery because of its unique
      ability to detect an occult residuum of hyperfunctioning parathyroid tissue. Use
      of this assay will obviate the need for frozen section in most routine cases. The
      test facilitates minimally invasive parathyroidectomy for single parathyroid
      adenomas, which, in turn, improves cost-effectiveness and cosmetic outcome. Its
      use in patients with known preoperative multiglandular disease is promising but
      requires further study.

PMID- 14567727
TI  - Five-year follow-up of routine outpatient test turnaround time: a College of
      American Pathologists Q-Probes study.
AB  - CONTEXT: Timely reporting of outpatient tests can increase efficiency of care and
      improve customer satisfaction. OBJECTIVES: We conducted a survey in 2002 to
      determine how quickly hospital-based laboratories turned around routine requests
      for 3 common assays and compared the results with a similar survey conducted in
      1997. DESIGN: One hundred eighteen laboratories prospectively recorded the
      collection-to-verification turnaround time for 9252 complete blood cell counts
      (CBCs), 8832 thyroid tests, and 9193 basic metabolic panels. RESULTS: The median
      facility reported all test results by 7:00 am of the weekday immediately after
      the date of specimen collection. The bottom 10% of institutions reported 99% of
      CBCs and basic metabolic panels within 1 day and 60% of thyroid tests within 1
      day. The 65 institutions that participated in both the 1997 and 2002 surveys
      showed significant overall improvement in turnaround time for all 3 types of
      tests (P <.001). In 2002, federal institutions had significantly slower
      turnaround times than nonfederal institutions for CBC tests (P <.001), thyroid
      tests (P =.03), and basic metabolic panels (P <.001). Other demographic and
      practice variables were not associated with turnaround time. CONCLUSION: The
      turnaround time of routine outpatient tests appears to have improved between 1997
      and 2002.

PMID- 14567728
TI  - Precision in gynecologic cytologic interpretation: a study from the College of
      American Pathologists Interlaboratory Comparison Program in Cervicovaginal
      Cytology.
AB  - CONTEXT: Numerous studies address the accuracy or positive predictive value of
      cytologic interpretations for defined histopathologic entities. The
      reproducibility (precision) of cytologic interpretation is less well defined.
      OBJECTIVE: To establish and compare the reproducibility (precision) of cytologic
      interpretation in gynecologic cytopathology, as reflected in the educational
      program of the College of American Pathologists Interlaboratory Comparison
      Program in Cervicovaginal Cytology (PAP). METHODS: The pathologists'
      interpretations for both validated (25 745 responses) and educational
      conventional (14 353 responses) slides in the PAP program for 2001 were analyzed.
      The frequency of exact matches between the reference and pathologists'
      interpretation for each of the cytologic interpretative categories was
      identified, and the cumulative distributions of exact match rates were derived.
      chi2 Tests by reference interpretations were used for cytodiagnostic categories,
      least and most reproducible groupings, and high-grade (HSIL) versus low-grade
      (LSIL) squamous intraepithelial lesions. RESULTS: Pathologists' interpretations
      of negative, Candida, Trichomonas, herpes, and LSIL were characterized by a high
      degree of exact matching, while interpretations of repair, HSIL, adenocarcinoma,
      and squamous cell carcinomas were characterized by a lesser degree of exact
      matching (reproducibility). Pathologists' cytologic interpretations of HSIL were
      significantly less reproducible than those of LSIL. CONCLUSION: The cytologic
      interpretations of the most significant categories (HSIL, squamous cell
      carcinoma, and adenocarcinoma) are less precise than those of specific infection
      (Candida, Trichomonas, and yeast), negative, and LSIL categories. Cytologic
      interpretations of LSIL are made with greater precision than those of HSIL and
      may represent a more appropriate endpoint to measure the precision performance of
      gynecologic cytology laboratories.

PMID- 14567730
TI  - Improving the autopsy rate in a teaching hospital.

PMID- 14567731
TI  - Ira Maximilian Altshuler: psychiatrist and pioneer music therapist.
AB  - The purpose of this study was to examine the life of Ira Maximilian Altshuler,
      psychiatrist and pioneer music therapist. In 1938, Dr. Altshuler initiated one of
      the first large-scale music therapy programs for mentally ill persons in the
      country at Detroit's Eloise Hospital. His innovative programs combined
      psychoanalytic techniques and music therapy methods specifically designed for use
      with large groups of clients. He later trained some of the first music therapy
      interns in the country, including Carol Collins, who served for many years as
      Professor of Music Therapy at Wayne State University, and Esther Goetz Gilliland,
      who later became President of NAMT. Dr. Altshuler promoted the practice and
      profession tirelessly, speaking to numerous audiences over the years and writing
      19 articles about music therapy. Altshuler participated in the National
      Association for Music Therapy (NAMT) organizational meeting held in New York City
      in 1950. An active member of the organization for many years, he served on the
      Research Committee and hosted the 1955 national NAMT conference in Detroit. Even
      after Altshuler's retirement from Eloise Hospital in 1963, he remained active in
      numerous civic, music, and music therapy activities until his death 5 year later.
      Ira Altshuler should be remembered along with other music therapists from the
      time-Willem Van de Wall, Harriet Ayer Seymour and others-who vigorously embraced
      and advanced the status of the profession.

PMID- 14567732
TI  - Relating improvisational music therapy with severely and multiply disabled
      children to communication development.
AB  - The effect of different levels of preintentional and intentional communication
      development on musical interaction with children with severe and multiple
      disabilities has not been explored in the music therapy literature. Aside from
      stage of communication development, what are the particular influences of
      disability on musical interaction with children who have preintentional and early
      intentional communication? A qualitative research project explored these issues.
      Ten school-aged children with severe and multiple disabilities participated in
      the project. The most common medical diagnosis was cerebral palsy. Analysis of
      video recordings and other data confirmed that the children's level of
      communication development was reflected in individual music therapy.
      Specifically, children at different levels of communication development varied in
      their abilities to initiate, anticipate, and sustain participation in turn
      taking, and to maintain attention to and engagement in the interaction. Both turn
      taking and playing and singing together were found to be important forms of
      communication during music therapy. Communication problems related to disability
      included: difficulties in using objects as a focus of joint attention,
      difficulties in interpreting the interactive environment, being sufficiently
      motivated to communicate, severely limited means of interaction, attaining and
      maintaining an appropriate level of arousal, and lack of interest in interaction
      and the outside environment. Further study of how music therapy can be related to
      general issues in communication for individuals with severe and multiple
      disabilities is recommended.

PMID- 14567733
TI  - The effects of a movement with music program on measures of balance and gait
      speed in healthy older adults.
AB  - A group of 16 healthy older adults participated in a movement with music program
      to enhance physical flexibility, balance, and gait speed. The program, designed
      by a Laban Movement Analyst, consisted of 14 movement sequences set to music
      composed to reflect the dynamics, rhythm, timing, and phrasing of the movements.
      After 5 weeks, individuals showed statistically significant increases in measures
      of one-foot stance balance, gait speed, and functional reach. From the 5th to the
      14th week, improvements continued in all measures but were not statistically
      significant.

PMID- 14567734
TI  - The effects of music listening after a stressful task on immune functions,
      neuroendocrine responses, and emotional states in college students.
AB  - The purpose of this study was to examine the effects of listening to high
      uplifting or low-uplifting music after a stressful task on (a) immune functions,
      (b) neuroendocrine responses, and (c) emotional states in college students.
      Musical selections that were evaluated as high-uplifting or low-uplifting by
      Japanese college students were used as musical stimuli. Eighteen Japanese
      subjects performed stressful tasks before they experienced each of these
      experimental conditions: (a) high-uplifting music, (b) low-uplifting music, and
      (c) silence. Subjects' emotional states, the Secretory IgA (S-IgA) level, active
      natural killer (NK) cell level, the numbers of T lymphocyte CD4+, CD8+, CD16+,
      dopamine, norepinephrine, and epinephrine levels were measured before and after
      each experimental condition. Results indicated low-uplifting music had a trend of
      increasing a sense of well-being. High-uplifting music showed trends of
      increasing the norepinephrine level, liveliness, and decreasing depression.
      Active NK cells were decreased after 20 min of silence. Results of the study were
      inconclusive, but high-uplifting and low-uplifting music had different effects on
      immune, neuroendocrine, and psychological responses. Classification of music is
      important to research that examines the effects of music on these responses.
      Recommendations for future research are discussed.

PMID- 14567735
TI  - Pathologic quiz case: a 70-year-old woman with an expansile lesion of the right
      anterior mandible. Periapical cemento-osseous dysplasia with superimposed chronic
      osteomyelitis.

PMID- 14567736
TI  - Pathologic quiz case: hypoplastic digit, diaphragmatic hernia, and agenesis of
      the corpus callosum in a 21(5/7)-week fetus. Fryns syndrome.

PMID- 14567737
TI  - Pathologic quiz case: a 54-year-old man with hypertension. Primary high-grade
      leiomyosarcoma of the IVC.

PMID- 14567738
TI  - Pathologic quiz case: a 49-year-old man with chronic cough and a left lung hilar
      mass. Tracheobronchial amyloidosis.

PMID- 14567739
TI  - Xanthelasma or xanthoma of the fallopian tube.
AB  - We report a case of a 24-year-old woman who presented with abdominal pain, a
      tense abdomen, and rebound tenderness. A vague, ill-defined mass was palpated,
      and an ultrasound examination revealed a cystic lesion in the left adnexal
      region. At laparotomy, a slightly dilated fallopian tube was seen and excised.
      Light microscopy showed intact fallopian tube mucosa, with a diffuse infiltrate
      of foam cells in the lamina propria. There were no associated inflammatory cells.
      The foam cells were positive for CD68 and negative for AE1/AE3. Discontinuous
      areas of the epithelium also showed epithelial cells with "foamy cytoplasm."
      These cells were negative for CD68 but positive for AE1/AE3. To our knowledge,
      this represents the first case of a fallopian tube xanthelasma that shows a
      resemblance to lesions encountered in the stomach. Fallopian tube xanthelasma
      must be distinguished from xanthogranulomatous salpingitis, which is associated
      with an inflammatory cell infiltrate, often including giant cells. However, this
      lesion may share pathogenetic similarities with xanthogranulomatous salpingitis,
      since both processes are mediated by inflammation.

PMID- 14567743
TI  - Lost dog.

PMID- 14567744
TI  - Narrow-spectrum histochemical staining of fungi.

PMID- 14567745
TI  - Pathologic quiz case: a 55-year-old woman with a history of treated Hodgkin
      disease and a persistent abdominal mass. Extranodal gastrointestinal Rosai
      Dorfman disease.

PMID- 14567746
TI  - Pathologic quiz case: an upper outer quadrant breast mass in a 47-year-old
      African American woman. Granular cell tumor.

PMID- 14567747
TI  - Pathologic quiz case: a woman with dysphagia and unusual histologic findings in
      the esophagus. Residual tracheobronchial remnants, consistent with the history of
      TEF. Tracheoesophageal fistula.

PMID- 14567748
TI  - Error management: theory and application in transfusion medicine at a tertiary
      care institution.

PMID- 14567749
TI  - Lymphangioma of the pancreas with "ovarian-like" mesenchymal stroma: a case
      report with emphasis on histogenesis.
AB  - Pancreatic lymphangiomas, which occur predominantly in women, are rare and
      account for only 1% of all lymphangiomas. The characteristic histologic features
      include multiple cysts lined by endothelial cells, irregularly distributed smooth
      muscle cells, and lymphoid aggregates in the wall of the cyst. We describe a 36
      year-old woman with lymphangioma of the pancreas with "ovarian-like" mesenchymal
      stroma in the wall. This stroma, composed of uncommitted mesenchymal cells, has
      not been described previously in the wall of pancreatic lymphangiomas. Multiple
      small lymphatic channels that are found in this stroma recapitulate the
      development of lymphatic channels in the embryo. Lymphangioma of the pancreas may
      arise from distension of these lymphatic channels. Pancreatic lymphangioma may,
      therefore, be a developmental anomaly rather than a true neoplasm.

PMID- 14567750
TI  - Metastatic foci of signet ring cell carcinoma in a tubular adenoma of the colon.
AB  - We describe a case of adenomatous polyp of the colon that harbored small foci of
      signet ring cell carcinoma. The patient was a 64-year-old woman with end-stage
      renal disease and sepsis who underwent colonoscopy to evaluate the possibility of
      pseudomembranous colitis. A polyp was found incidentally in the right colon and a
      biopsy was performed. Histologic examination of the polyp revealed typical
      features of tubular adenoma without evidence of high-grade dysplasia. However, 2
      small foci of signet ring cell carcinoma were identified that infiltrated the
      lamina propria. In contrast to adenomatous epithelium, the signet ring cells were
      immunohistochemically positive for cytokeratin 7 and negative for cytokeratin 20,
      suggesting a metastasis rather than a primary tumor. Multiple random biopsies
      from the right and left colon, as well as the ileum, exhibited no histologic
      evidence of malignancy. Subsequently, signet ring cell carcinoma with similar
      morphology and identical immunophenotype was detected in biopsies from the
      endometrium, an unusual location for primary signet ring cell carcinoma.
      Preliminary workup excluded the breast as a possible primary site, but further
      investigation was not possible because of the patient's death with no autopsy
      granted. To the best of our knowledge, this is the first reported case of
      metastatic signet ring cell carcinoma to an adenomatous polyp of the colon. This
      case illustrates the necessity of submitting all polyps entirely and the
      importance of examining them carefully.

PMID- 14567751
TI  - Simultaneous presentation of multiple myeloma and acute monocytic leukemia.
AB  - Acute leukemia frequently has been described as a late complication of
      chemotherapy with alkylating agents in patients treated for multiple myeloma.
      However, the simultaneous occurrence of multiple myeloma and acute leukemia in
      the same patient, without previous exposure to chemotherapy, is a rare
      association. We describe a case of concomitant involvement by multiple myeloma
      and acute monocytic leukemia. To our knowledge, only 9 such cases have been
      reported in the literature to date. We discuss the criteria used in diagnosing
      the 2 separate diseases and the possible mechanisms responsible for this
      occurrence.

PMID- 14567752
TI  - Ampullary pancreatoblastoma in an elderly patient: a case report and review of
      the literature.
AB  - Pancreatoblastoma, generally regarded as a pediatric malignant tumor, is rarely
      found in the adult population. Only 13 adults with pancreatoblastoma, ranging in
      age from 19 to 68 years, have previously been reported in the world literature. A
      diagnosis of pancreatoblastoma relies on characteristic histologic features,
      including epithelial differentiation and, more importantly, squamoid
      differentiation. Despite aggressive therapy, adults with pancreatoblastoma have a
      poor outcome. We describe a 78-year-old woman who presented with painless
      jaundice and was found on abdominal computed tomographic scan to have a 2.7-cm
      ampullary mass. The patient underwent successful pancreaticoduodenectomy.
      Pathologic examination of the resected tumor revealed findings characteristic of
      pancreatoblastoma. The tumor formed acinar and glandular structures, solid areas,
      and contained many "squamoid corpuscles," a defining feature of
      pancreatoblastoma. The tumor cells also showed acinar and ductal phenotype by
      immunohistochemistry. To the best of our knowledge, this case represents the
      oldest patient with pancreatoblastoma to be described in the literature to date
      and the first to occur in the ampulla of Vater. We review previously published
      cases and discuss the clinical and histopathologic features of adult
      pancreatoblastoma.

PMID- 14567753
TI  - Three-millimeter apocrine adenoma in a man: a case report and review of the
      literature.
AB  - We describe a rare case of apocrine adenoma of the breast in a 45-year-old man.
      The patient presented with a tender lump in his left breast that had been present
      for 6 months. A mammogram identified a 3-mm nodular density in the breast, which
      was described as a hypoechoic nodule on ultrasound. Microscopic examination of
      tissue from an excisional biopsy revealed a 3-mm group of benign glands with
      abundant granular, eosinophilic cytoplasm and apical luminal blebbing, consistent
      with an apocrine adenoma. After reviewing other reported apocrine adenomas in the
      literature, we determined that our case was the smallest detected apocrine
      adenoma to be reported to date.

PMID- 14567755
TI  - Hormonal regulation of phospholipase Cepsilon through distinct and overlapping
      pathways involving G12 and Ras family G-proteins.
AB  - PLCepsilon (phospholipase Cepsilon) is a novel PLC that has a CDC25 guanine
      nucleotide exchange factor domain and two RA (Ras-association) domains of which
      the second (RA2) is critical for Ras activation of the enzyme. In the present
      studies, we examined hormonal stimulation to elucidate receptor-mediated pathways
      that functionally regulate PLCepsilon. We demonstrate that EGF (epidermal growth
      factor), a receptor tyrosine kinase agonist, and LPA (lysophosphatidic acid), S1P
      (sphingosine 1-phosphate) and thrombin, GPCR (G-protein-coupled receptor)
      agonists, stimulate PLCepsilon overexpressed in COS-7 cells. EGF stimulated
      PLCepsilon in an RA2-dependent manner through Ras and Rap. In contrast, LPA, S1P
      and thrombin stimulated PLCepsilon by both RA2-independent and -dependent
      mechanisms. To determine the G-proteins that mediate the effects of these GPCR
      agonists, we co-expressed constitutively active G-proteins with PLCepsilon and
      found that G(alpha12), G(alpha13), Rho, Rac and Ral stimulate PLCepsilon in an
      RA2-independent manner; whereas TC21, Rap1A, Rap2A and Rap2B stimulate PLCepsilon
      in an RA2-dependent manner similar to H-Ras. Of these G-proteins, we show that
      G(alpha12)/G(alpha13) and Rap partly mediate the effects of LPA, S1P and thrombin
      to stimulate PLCepsilon. In addition, the stimulation by LPA and S1P is also
      partly sensitive to pertussis toxin. These studies demonstrate diverse hormonal
      regulation of PLCepsilon by distinct and overlapping pathways.

PMID- 14567754
TI  - How versatile are inositol phosphate kinases?
AB  - This review assesses the extent and the significance of catalytic versatility
      shown by several inositol phosphate kinases: the inositol phosphate multikinase,
      the reversible Ins(1,3,4) P (3)/Ins(3,4,5,6) P (4) kinase, and the kinases that
      synthesize diphosphoinositol polyphosphates. Particular emphasis is placed upon
      data that are relevant to the situation in vivo. It will be shown that catalytic
      promiscuity towards different inositol phosphates is not typically an
      evolutionary compromise, but instead is sometimes exploited to facilitate tight
      regulation of physiological processes. This multifunctionality can add to the
      complexity with which inositol signalling pathways interact. This review also
      assesses some proposed additional functions for the catalytic domains, including
      transcriptional regulation, protein kinase activity and control by molecular
      'switching', all in the context of growing interest in 'moonlighting' (gene
      sharing) proteins.

PMID- 14567756
TI  - Functional reconstitution, gene isolation and topology modelling of porins from
      Burkholderia pseudomallei and Burkholderia thailandensis.
AB  - The sequences for Omp38 from Burkholderia pseudomallei and Burkholderia
      thailandensis have been deposited in the DDBJ, EMBL, GenBank(R) and GSDB
      Nucleotide Sequence Databases under the accession numbers AY312416 and AY312417
      respectively. The intracellular pathogen Burkholderia pseudomallei is the
      causative agent of tropical melioidosis, and Burkholderia thailandensis is a
      closely-related Gram-negative bacterium that does not cause serious disease. Like
      other bacteria, the major outer membrane (OM) porins of Burkholderia strains, Bps
      Omp38 and Bth Omp38 may have roles in antibiotic resistance and immunity. We
      purified both proteins and found them to be immunologically related, SDS
      resistant, heat-sensitive trimers with M (r) of approx. 110000. In functional
      liposome-swelling assays, both proteins showed similar permeabilities for small
      sugar molecules, compatible with a pore diameter of between 1.2 and 1.6 nm.
      Secondary structure analysis by FTIR (Fourier-transform infrared) spectroscopy
      revealed almost identical spectra with predominantly beta-sheet structures,
      typical of bacterial porins. MALDI-TOF (matrix-assisted laser-desorption
      ionization-time of flight) MS and ESI/MS (electrospray ionization MS) analysis of
      each protein showed extensive sequence similarities to the OpcP1 porin from
      Burkholderia cepacia (later found to be 76.5% identical). Based on information
      from the incomplete B. pseudomallei genome-sequencing project, the genes encoding
      Omp38 were identified and amplified by PCR from B. pseudomallei and B.
      thailandensis genomic DNA. The nucleotide sequences are 99.7% identical, and the
      predicted processed proteins are 100% identical. Topology prediction and
      molecular modelling suggest that this newly-isolated and cloned porin is a 16
      stranded beta-barrel and the external loops of the protein could be important
      determinants of the immune response to infection.

PMID- 14567757
TI  - A neuronal-specific differentiation protein that directly modulates retinoid
      receptor transcriptional activation.
AB  - BACKGROUND: The specificity of a nuclear receptor's ability to modulate gene
      expression resides in its ability to bind a specific lipophilic ligand, associate
      with specific dimerization partners and bind specific DNA sequences in the
      promoter regions of genes. This sequence of events appears to be the basis for
      targeting an additional regulatory complex composed of a variety of protein and
      RNA components that deliver signals for facilitation or inhibition of the RNA
      polymerase complex. Characterization of the tissue and cell-specific components
      of these coregulatory complexes appear to be integral to our understanding of
      nuclear receptor regulation of transcription. RESULTS: A novel yeast screen
      sensitive to retinoid-X receptor (RXR) transcriptional activation resulted in the
      isolation of the rat homologue of the mouse NPDC-1 gene. NPDC-1 has been shown to
      be involved in the control of neural cell proliferation and differentiation,
      possibly through interactions with the cell cycle promoting transcription factor
      E2F-1. Although the amino acid sequence of NPDC-1 is highly conserved between
      mouse, rat and human homologues, their tissue specific expression was seen to
      vary. A potential for direct protein:protein interaction between NPDC-1, RXR and
      retinoic acid receptor beta (RARbeta) was observed in vitro and NPDC-1
      facilitated RXR homodimer and RAR-RXR heterodimer DNA binding in vitro.
      Expression of NPDC-1 was also observed to repress transcription mediated by
      retinoid receptors as well as by several other nuclear receptor family members,
      although not in a universal manner. CONCLUSIONS: These results suggest that NPDC
      1, through direct interaction with retinoid receptors, functions to enhance the
      transcription complex formation and DNA binding function of retinoid receptors,
      but ultimately repress retinoid receptor-mediated gene expression. As with NPDC
      1, retinoids and their receptors have been implicated in brain development and
      these data provide a point of convergence for NPDC-1 and retinoid mediation of
      neuronal differentiation.

PMID- 14567758
TI  - Sustained inhibition of rat myometrial gap junctions and contractions by lindane.
AB  - BACKGROUND: Gap junctions increase in size and abundance coincident with
      parturition, forming an intercellular communication network that permits the
      uterus to develop the forceful, coordinated contractions necessary for delivery
      of the fetus. Lindane, a pesticide used in the human and veterinary treatment of
      scabies and lice as well as in agricultural applications, inhibits uterine
      contractions in vitro, inhibits myometrial gap junctions, and has been associated
      with prolonged gestation length in rats. The aim of the present study was to
      investigate whether brief exposures to lindane would elicit sustained inhibition
      of rat uterine contractile activity and myometrial gap junction intercellular
      communication. METHODS: To examine effects on uterine contraction, longitudinal
      uterine strips isolated from late gestation (day 20) rats were exposed to lindane
      in muscle baths and monitored for changes in spontaneous phasic contractions
      during and after exposure to lindane. Lucifer yellow dye transfer between
      myometrial cells in culture was used to monitor gap junction intercellular
      communication. RESULTS: During a 1-h exposure, 10 micro M and 100 micro M lindane
      decreased peak force and frequency of uterine contraction but 1 micro M lindane
      did not. After removal of the exposure buffer, contraction force remained
      significantly depressed in uterine strips exposed to 100 micro M lindane,
      returning to less than 50% basal levels 5 h after cessation of lindane exposure.
      In cultured myometrial myocytes, significant sustained inhibition of Lucifer
      yellow dye transfer was observed 24 h after lindane exposures as brief as 10 min
      and as low as 0.1 micro M lindane. CONCLUSION: Brief in vitro exposures to
      lindane have long-term effects on myometrial functions that are necessary for
      parturition, inhibiting spontaneous phasic contractions in late gestation rat
      uterus and gap junction intercellular communication in myometrial cell cultures.

PMID- 14567759
TI  - Aphrodisiac activity of 50% ethanolic extracts of Myristica fragrans Houtt.
      (nutmeg) and Syzygium aromaticum (L) Merr. & Perry. (clove) in male mice: a
      comparative study.
AB  - BACKGROUND: Spices are considered as sexual invigorators in the Unani System of
      Medicine. In order to explore the sexual function improving effect of Myristica
      fragrans Houtt. (nutmeg) and Syzygium aromaticum (L) Merr. & Perry. (clove) an
      experimental study was conducted in normal male mice. METHODS: The extracts (50%
      ethanolic) of nutmeg and clove were administered (500 mg/kg; p.o.) to different
      groups of male Swiss mice. Mounting behaviour, mating performance, and general
      short term toxicity of the test drugs were determined and compared with the
      standard drug Penegra (Sildenafil citrate). RESULTS: The extracts of the nutmeg
      and clove were found to stimulate the mounting behaviour of male mice, and also
      to significantly increase their mating performance. The drugs were devoid of any
      conspicuous general short term toxicity. CONCLUSION: The extracts (50% ethanolic)
      of nutmeg and clove enhanced the sexual behaviour of male mice.

PMID- 14567760
TI  - Epidemiology of cardiovascular risk factors in Greece: aims, design and baseline
      characteristics of the ATTICA study.
AB  - BACKGROUND: In an attempt to evaluate the levels of several cardiovascular risk
      factors in Greece we conducted a population-based health and nutrition survey,
      the "ATTICA study". In this work we present the design and the methodology of the
      study, as well as the status of various baseline characteristics of the
      participants. METHODS: From May 2001 to December 2002 we randomly enrolled 1514
      adult men and 1528 adult women, stratified by age--gender (census 2000), from the
      greater area of Athens. More than 300 demographic, lifestyle, behavioral,
      dietary, clinical and biochemical variables have been recorded. RESULTS:
      Regarding the frequency of the classical cardiovascular risk factors we observed
      that 51% of men and 39% of women reported smokers (p < 0.05), 37% of men and 25%
      of women were defined as hypertensives (p < 0.05), 46% of men and 40% of women
      had total serum cholesterol levels above 200 mg/dl (p < 0.05) and 8% of men and
      6% of women had history of diabetes mellitus. Moreover, 20% of men and 15% of
      women were obese (p < 0.05), while men were more physically active as compared to
      women (42% vs. 39%, p < 0.05). 19% of men and 38% of women had mild to severe
      depressive symptoms (p < 0.01). Finally, 72 men (5%) and 45 (3%) women reported
      history of coronary heart disease at entry evaluation. CONCLUSIONS: The
      prevalence of the common cardiovascular risk factors in our population seems
      high. As a consequence a considerable proportion of Greek adults are at "high
      risk" for future cardiovascular events.

PMID- 14567761
TI  - No association between the sigma receptor type 1 gene and schizophrenia: results
      of analysis and meta-analysis of case-control studies.
AB  - BACKGROUND: Several lines of evidence have supported possible roles of the sigma
      receptors in the etiology of schizophrenia and mechanisms of antipsychotic
      efficacy. An association study provided genetic evidence that the sigma receptor
      type 1 gene (SIGMAR1) was a possible susceptibility factor for schizophrenia,
      however, it was not replicated by a subsequent study. It is necessary to evaluate
      further the possibility that the SIGMAR1 gene is associated with susceptibility
      to schizophrenia. METHODS: A case-control association study between two
      polymorphisms of the SIGMAR1 gene, G-241T/C-240T and Gln2Pro, and schizophrenia
      in Japanese population, and meta-analysis including present and previous studies.
      RESULTS: There was no significant association of any allele or genotype of the
      polymorphisms with schizophrenia. Neither significant association was observed
      with hebephrenic or paranoid subtype of schizophrenia. Furthermore, a meta
      analysis including the present and previous studies comprising 779 controls and
      636 schizophrenics also revealed no significant association between the SIGMAR1
      gene and schizophrenia. CONCLUSION: In view of this evidence, it is likely that
      the SIGMAR1 gene does not confer susceptibility to schizophrenia.

PMID- 14567762
TI  - Rectal cancer in Luxembourg : a national population-based data report, 1988-1998.
AB  - BACKGROUND: Morphologic criteria which might help to support the need for a
      preventive strategy for early detection of rectal cancer were analysed.
      Population-based data on rectal adenomas with high-grade dysplastic changes (n =
      199) and invasive adenocarcinomas (n = 912) registered by the national
      Morphologic Tumour Registry (MTR) and diagnosed in a central department of
      pathology in Luxembourg between 1988 and 1998 were considered. METHODS: The
      analysis concerned time trends in frequency, crude incidence, tumour-stage, the
      rectal "high-grade" adenoma/invasive adenocarcinoma-ratio and the survival rates.
      Histopathological tumour-stage parameters (UICC/AJCC, 1997) in a consecutive
      series of 641 resected rectal cancers and their relationship with the observed
      patient survival are investigated. RESULTS: The majority of invasive
      adenocarcinomas are diagnosed at a late stage (i.e. Stage II and III) into
      contrast with the highly significant increase (355 %) in frequency of rectal high
      grade adenomas (Stage 0). During the two-time periods 1988-1992 and 1994-1998
      Stage I and Stage IV-cases decreased by 11 % and 47 % respectively. Tumour-stage
      correlates with prognosis. The rectal high-grade adenoma / invasive
      adenocarcinoma-ratio improved significantly over the last five years. CONCLUSION:
      Over the study period, there has been a highly significant rise in the incidence
      of resected rectal adenomas with high-grade intraepithelial neoplasia. The ratio
      of early tumours to invasive cancers has risen while the numbers of colonoscopies
      and rectoscopies remained unchanged respectively decreased. As the number of
      advanced tumour-stages remained stable, mass-screening procedures focusing on the
      fifty to sixty age group should be reinforced.

PMID- 14567763
TI  - Alternatives for logistic regression in cross-sectional studies: an empirical
      comparison of models that directly estimate the prevalence ratio.
AB  - BACKGROUND: Cross-sectional studies with binary outcomes analyzed by logistic
      regression are frequent in the epidemiological literature. However, the odds
      ratio can importantly overestimate the prevalence ratio, the measure of choice in
      these studies. Also, controlling for confounding is not equivalent for the two
      measures. In this paper we explore alternatives for modeling data of such studies
      with techniques that directly estimate the prevalence ratio. METHODS: We compared
      Cox regression with constant time at risk, Poisson regression and log-binomial
      regression against the standard Mantel-Haenszel estimators. Models with robust
      variance estimators in Cox and Poisson regressions and variance corrected by the
      scale parameter in Poisson regression were also evaluated. RESULTS: Three
      outcomes, from a cross-sectional study carried out in Pelotas, Brazil, with
      different levels of prevalence were explored: weight-for-age deficit (4%), asthma
      (31%) and mother in a paid job (52%). Unadjusted Cox/Poisson regression and
      Poisson regression with scale parameter adjusted by deviance performed worst in
      terms of interval estimates. Poisson regression with scale parameter adjusted by
      chi2 showed variable performance depending on the outcome prevalence. Cox/Poisson
      regression with robust variance, and log-binomial regression performed equally
      well when the model was correctly specified. CONCLUSIONS: Cox or Poisson
      regression with robust variance and log-binomial regression provide correct
      estimates and are a better alternative for the analysis of cross-sectional
      studies with binary outcomes than logistic regression, since the prevalence ratio
      is more interpretable and easier to communicate to non-specialists than the odds
      ratio. However, precautions are needed to avoid estimation problems in specific
      situations.

PMID- 14567764
TI  - Is combined estrogen/progestogen hormone therapy worth the risk?

PMID- 14567765
TI  - Imaging the brain in healthy postmenopausal users and non-users of hormone
      replacement therapy.

PMID- 14567766
TI  - Progesterone creams: do they work?

PMID- 14567767
TI  - Hormone replacement therapy in climacteric and aging brain. International
      Menopause Society Expert Workshop, 15-18 March 2003, Pisa, Italy.

PMID- 14567768
TI  - Plasma leptin in postmenopausal women with coronary artery disease: effect of
      transdermal 17beta-estradiol and intermittent medroxyprogesterone acetate.
AB  - OBJECTIVES: In the present study, the relationship between plasma leptin and
      other cardiovascular risk factors in high-risk postmenopausal women was assessed,
      as well as the effect of transdermal 17beta-estradiol unopposed or in combination
      with intermittent medroxyprogesterone acetate (MPA) on plasma leptin. METHODS:
      Postmenopausal women (n = 118) with coronary artery disease (CAD) were
      consecutively recruited from women admitted to hospital for coronary angiography.
      They were randomized to estradiol plus intermittent MPA or to a control group,
      and investigated at study inclusion, and after 3 and 12 months. RESULTS: A strong
      relationship was found between leptin and body mass index (r = 0.69, p < 0.001).
      Leptin was related to lipid fractions (high-density lipoprotein cholesterol: r = 
      0.33, p < 0.001; apolipoprotein A: r = -0.28, p = 0.004; and triglycerides: r =
      0.27, p = 0.003) and indices of glucose metabolism (C-peptide: r = 0.47, p <
      0.001; fasting insulin: r = 0.42, p < 0.001; glucose: r = 0.25, p = 0.008;
      insulin resistance: r = 0.45, p < 0.001; and insulin secretion: r = 0.36, p <
      0.001). In a multiple regression model, only body mass index (p < 0.001) and C
      peptide (p = 0.002) remained as independent factors for leptin levels. Despite
      the association with sex hormone-binding globulin (r = 0.30, p = 0.001), no
      effect on leptin levels was observed with either unopposed transdermal estradiol
      or estradiol combined with MPA. CONCLUSION: Plasma leptin is related to other
      cardiovascular risk factors in postmenopausal women with CAD, but seems to be
      unaffected by transdermal 17beta-estradiol administration.

PMID- 14567769
TI  - Effects on climacteric symptoms, bone and lipoprotein metabolism of hormone
      replacement therapy delivered by estradiol-releasing intravaginal rings: a pilot
      study.
AB  - OBJECTIVE: To assess the efficacy and tolerability of intravaginal rings (IVRs)
      delivering estradiol. DESIGN: This was a dose-escalating, continuous-dosing,
      pilot study. METHODS: Sixteen women post surgical menopause were recruited at a
      hospital-based menopause clinic. Over 20 weeks, each patient had IVR devices
      releasing 50, 75, 100, 150 and 200 mug/day of estradiol inserted consecutively at
      4-weekly intervals. MAIN OUTCOME MEASURES: Climacteric symptoms were assessed,
      and levels of serum estradiol, lipoproteins and biochemical indices of bone
      turnover were estimated prior to insertion of the first IVR and at each monthly
      visit, when the IVR was changed to one of a higher dose. The susceptibility of
      low-density lipoprotein (LDL) to oxidation was assessed at 0, 12 and 20 weeks.
      RESULTS: Twelve women completed the study. The rings were well tolerated and
      serum estradiol levels increased in parallel with each increasing dose. Vasomotor
      and psychological symptoms and loss of libido were reduced by 76% (p < 0.001),
      44% (p < 0.001) and 44% (p < 0.05), respectively, by the end of the study. There
      were no significant changes in levels of serum lipoproteins, although the ratio
      of LDL cholesterol to high-density lipoprotein cholesterol decreased by 7.2% (p =
      0.01) after 20 weeks. The susceptibility of LDL to oxidation did not change.
      Urinary excretion of both calcium and deoxypyridinoline cross-links decreased
      significantly (p < 0.001), indicating a reduction in bone resorption.
      CONCLUSIONS: The rings were effective in controlling climacteric symptoms and had
      beneficial effects on bone metabolism, but no significant effects on lipoprotein
      levels or the susceptibility of LDL to oxidation.

PMID- 14567770
TI  - Comparison of the proliferative effects of estradiol and conjugated equine
      estrogens on human breast cancer cells and impact of continuous combined
      progestogen addition.
AB  - OBJECTIVES: So far, most epidemiological studies investigating breast cancer risk
      and hormone replacement therapy have been conducted with conjugated equine
      estrogens (CEE). Recent trials indicate that the addition of progestogens may
      increase breast cancer risk. In the present study, we compared the effects of the
      human estrogen 17beta-estradiol (E(2)) with those of the main equine components
      of CEE, i.e. equilin (Eq) and 17alpha-dihydroequilin (Dheq) on the proliferation
      of human breast cancer cells. The proliferative effect of progestogen addition
      was also investigated. MATERIALS AND METHODS: The well-established human breast
      cancer cell line MCF-7 was used as an in vitro model. The proliferative effect of
      E(2), Eq and Dheq was tested in the concentration range 0.01-10 nmol/l. The
      progestogens progesterone, medroxyprogesterone acetate (MPA) and norethisterone
      (NET) were continuously combined with 0.1 nmol/l estrogen at concentrations of
      0.01 nmol/l, 1 nmol/l, 0.1 mumol/l and 10 mumol/l. Proliferation was measured
      after 7 days by the adenosine triphosphate (ATP) chemosensitivity test. RESULTS:
      All three estrogens increased the proliferation of MCF-7 cells by between 40 and
      180%. The most proliferatively potent estrogen was E(2), followed by Eq and Dheq,
      which showed a slightly lower proliferative activity than E(2). The addition of
      progesterone inhibited E(2)-induced proliferation by about 30%, but only at the
      high non-physiological concentration of 10 mumol/l. All three progestogens
      inhibited Eq-induced proliferation, although their effect tended to be low, with
      values between 5 and 40%. No progestogen reduced Dheq-induced proliferation by
      more than 20%. In contrast, MPA slightly increased the proliferation rate by
      about 5% at the high physiological concentration of 0.1 mumol/l when combined
      with Dheq. The same held true when MPA and NET were added at the high
      pharmacological concentration of 10 mumol/l, causing increases of about 10%.
      CONCLUSIONS: Our results indicate that equine estrogens have a proliferative
      action similar to that of 17beta-estradiol. Continuous addition of progestogens
      does not result in any major reduction of proliferative potency. Some
      progestogens may even enhance the estrogen-induced proliferation of pre-existing
      breast cancer cells, particularly when combined with certain equine estrogens.
      However, in none of the tested circumstances do progestogens increase the
      proliferative effect of estradiol, and progesterone has no deleterious effect
      even at pharmacological levels, in contrast to progestogens.

PMID- 14567771
TI  - Acute effects of tibolone on cerebral vascular reactivity in vitro.
AB  - OBJECTIVE: To evaluate the acute effects of tibolone and its metabolites on
      cerebral vascular reactivity in vitro. METHODS: Ring segments of the posterior
      cerebral artery from female rabbits were mounted in myographs for isometric
      tension recordings. Concentration-response curves with tibolone, 3alpha-OH
      tibolone, 3beta-OH-tibolone, Delta(4) isomer and 17beta-estradiol were obtained
      before and after addition of the NO blocker N(omega)-nitro-L-arginine methyl
      ester (L-NAME, 10(-4) mol/l) or the potassium-channel blocker tetraethylammonium
      chloride (TEA, 10(-2) mol/l). Additionally, the effects of the hormones on the
      concentration-response curves with calcium were examined. RESULTS: Tibolone and
      its metabolites induced a concentration-dependent relaxation comparable to that
      of 17beta-estradiol (area under the curve (AUC); tibolone vs. 17beta-estradiol:
      242 vs. 251; p < 0.05, analysis of variance). L-NAME increased the AUC for all
      substances compared with controls (p < 0.05, Student's t test), except for 17beta
      estradiol. Preincubation with TEA induced no changes. The concentration-dependent
      contraction curves with calcium were shifted rightward by all hormones.
      CONCLUSIONS: The study demonstrates that the acute relaxation induced by tibolone
      and its metabolites in cerebral arteries in vitro is comparable to that with
      17beta-estradiol, and seems to be mediated by inhibition of voltage-gated calcium
      channels and possibly partly by a nitric oxide-dependent mechanism.

PMID- 14567772
TI  - Vitamin C improves endothelial function in healthy estrogen-deficient
      postmenopausal women.
AB  - OBJECTIVE: Estrogen deficiency is associated with increased cardiovascular risk
      and endothelial dysfunction. Improvements in endothelial function with
      antioxidants, including vitamin C, have been reported. We aimed to determine the
      acute effect of vitamin C on endothelial function in healthy women with
      established menopause. SUBJECTS: Subjects (aged 47-59 years) were at least 1 year
      postmenopause. Ten (serum estradiol < 50 pmol/l) were not receiving hormone
      replacement therapy, while eight hysterectomized subjects received subcutaneous
      estradiol. DESIGN: Forearm blood flow (FBF; strain-gauge plethysmography)
      responses to intrabrachial artery infusions of incremental doses of acetylcholine
      (endothelium-dependent vasodilation) and sodium nitroprusside (endothelium
      independent vasodilation) were determined at baseline, and following 1.5 g
      vitamin C given intravenously. RESULTS: At baseline, estrogen-treated subjects
      had a lower index of insulin resistance (homeostasis model assessment, HOMA) and
      lower fibrinogen than those of estrogen deficient subjects. There was a trend
      towards higher baseline FBF and larger baseline FBF response to acetylcholine in
      estrogen-treated subjects. FBF responses to acetylcholine were significantly
      enhanced after vitamin C in estrogen-deficient subjects (area under the dose
      response curve (AUC): estrogen-deficient 9.9 +/- 2.6 vs. 15.1 +/- 3.2 (mean +/-
      SEM), p = 0.02; estrogen-treated 17.0 +/- 2.9 vs. 21.0 +/- 3.2, p = 0.07).
      Resting FBF and response to sodium nitroprusside were unchanged in either group
      by vitamin C. Plasminogen activator inhibitor-1 levels fell after vitamin C in
      the estrogen-deficient group (17.0 +/- 1.6 vs. 14.7 +/- 0.9 IU/ml, p = 0.03).
      CONCLUSIONS: These results indicate that endothelial function may be improved
      acutely by antioxidant treatment in postmenopausal women with established
      estrogen deficiency.

PMID- 14567774
TI  - The new terminology.

PMID- 14567773
TI  - Effect of raloxifene on sexual function in postmenopausal women.
AB  - OBJECTIVE: To determine the effects of raloxifene on sexual function in
      postmenopausal women with pre-existing vaginal atrophy treated with vaginal
      estrogen cream. METHODS: A total of 187 naturally postmenopausal women, 42-80
      years of age, with signs of genitourinary atrophy were enrolled in this 6-month,
      multicenter, parallel-group study. Subjects were randomized to oral raloxifene
      HCl 60 mg daily or matching placebo; the same subjects were also randomized to
      receive one application of either vaginal conjugated estrogen cream 0.5 g twice
      weekly for 6 months or non-hormonal vaginal moisturizer twice weekly for 3
      months, followed by conjugated estrogen cream for 3 months. Both investigators
      and subjects were masked to the identity of the oral medication. The vaginal
      preparations were administered in an open-label fashion. The Sexual Activity
      Questionnaire (SAQ) was administered at baseline and at 3 and 6 months. Safety
      was assessed throughout the study. RESULTS: A total of 102 women were sexually
      active at baseline and, of these, 82 were also sexually active at the 6-month end
      point. At 6 months, raloxifene and placebo, in the presence of vaginal conjugated
      estrogen cream, were both associated with improvement from baseline in vaginal
      dryness and reduced discomfort during sexual activity. There were no significant
      differences between raloxifene and placebo groups in any SAQ item. Enjoyment of
      sexual activity significantly increased from baseline with raloxifene but not
      with placebo. No difference in adverse events was observed between groups.
      CONCLUSION: Raloxifene had no negative effects on sexual function in
      postmenopausal women with vaginal atrophy who were treated concomitantly with
      vaginal estrogen cream.

PMID- 14567776
TI  - Identification of gap junction blockers using automated fluorescence microscopy
      imaging.
AB  - Gap junctions coordinate electrical signals and facilitate metabolic
      synchronization between cells. In this study, the authors have developed a novel
      assay for the identification of gap junction blockers using fluorescence
      microscopy imaging-based high-content screening technology. In the assay, the
      communication between neighboring cells through gap junctions was measured by
      following the redistribution of a fluorescent marker. The movement of calcein dye
      from dye-loaded donor cells to dye-free acceptor cells through gap junctions
      overexpressed on cell surface membranes was monitored using automated
      fluorescence microscopy imaging in a high-throughput compatible format. The
      fluorescence imaging technology consisted of automated focusing, image
      acquisition, image processing, and data mining. The authors have successfully
      performed a high-throughput screening of a 486,000- compound program with this
      assay, and they were able to identify false positives without additional
      experiments. Selective and pharmacologically interesting compounds were
      identified for further optimization.

PMID- 14567777
TI  - Comparative analysis of functional assays for characterization of agonist ligands
      at G protein-coupled receptors.
AB  - A variety of functional assays are available for agonist or antagonist screening
      of G protein-coupled receptors (GPCRs), but it is a priori not predictable which
      assay is the most suitable to identify agonists or antagonists of GPCRs with
      therapeutic value in humans. More specifically, it is not known how a given set
      of GPCR agonists compares in different functional assays with respect to potency
      and efficacy and whether the level of the signaling cascade that is analyzed has
      any impact on the detection of agonistic responses. To address this question, the
      authors used the recently cloned human S1P(5) receptor as a model and compared a
      set of 3 lipid ligands (sphingosine 1-phosphate [S1P], dihydro sphingosine 1
      phosphate [dhS1P], and sphingosine) in 5 different functional assays: GTPgammaS
      binding, inhibition of adenylyl cyclase activity, mobilization of intracellular
      Ca(2+) via the FLIPR and aequorin technology, and MAP kinase (ERK1/2) activation.
      S1P induced agonistic responses in all except the ERK1/2 assays with EC(50)
      values varying by a factor of 10. Whereas dhS1P was identified as a partial
      agonist in the GTPgammaS assay, it behaved as a full agonist in all other
      settings. Sphingosine displayed partial agonistic activity exclusively in
      GTPgammaS binding assays. The findings suggest that assays in a given cellular
      background may vary significantly with respect to suitability for agonist finding
      and that ligands producing a response may not readily be detectable in all
      agonist assays.

PMID- 14567778
TI  - Generation of stably transfected Mammalian cell lines as fluorescent screening
      assay for NF-kappaB activation-dependent gene expression.
AB  - Cellular stress protection responses lead to increased transcription of several
      genes via modulation of transcription factors. Activation of the Nuclear Factor
      kappaB (NF-kappaB) pathway as a possible antiapoptotic route represents one
      important cellular stress response. To identify conditions that are capable of
      modifying this pathway, a screening assay for detection of NF-kappaB-dependent
      gene activation using the reporter protein Enhanced Green Fluorescent Protein
      (EGFP) and its destabilized variant (d2EGFP) was developed. Human Embryonic
      Kidney (HEK/293) cells were stably transfected with a vector carrying EGFP or
      d2EGFP under control of a synthetic promoter containing 4 copies of the NF-kappaB
      response element. Treatment with tumor necrosis factor alpha (TNF-alpha) gave
      rise to substantial EGFP/d2EGFP expression in up to 90% of the cells and was
      therefore used to screen different stably transfected clones for induction of NF
      kappaB-dependent gene expression. The time course of NF-kappaB activation leading
      to d2EGFP expression was measured in an oligonucleotide-based NF-kappaB-ELISA. NF
      kappaB binding in-creased after 15-min incubation with TNF-alpha. In parallel,
      d2EGFP increased after 3 h and reached its maximum at 24 h. These results show
      (1) the time lag between NF-kappaB activation and d2EGFP transcription,
      translation, and protein folding and (2) the increased reporter gene expression
      after treatment with TNF-alpha to be caused by the activation of NF-kappaB. The
      detection of d2EGFP expression required FACS analysis or fluorescence microscopy,
      while EGFP could also be measured in the microplate reader, rendering the assay
      useful for high-throughput screening.

PMID- 14567779
TI  - A homogeneous 384-well high-throughput binding assay for a TNF receptor using
      alphascreen technology.
AB  - To take advantage of the growing knowledge of cellular signaling pathways, modern
      day drug discovery faces an increasing challenge to develop assays to screen for
      compounds that modulate protein-protein interactions. One bottleneck in achieving
      this goal is a lack of suitable and robust assay technologies amenable to a high
      throughput format. In this report, we describe how we utilized Alphascreen trade
      mark technology to develop a high-throughput assay to monitor ligand binding to a
      member of the tumor necrosis factor receptor superfamily. We expressed a fusion
      protein consisting of the extracellular domain of the OX40 receptor with the
      constant domains of human IgG. In the presence of OX40 ligand, we determined a
      binding affinity constant consistent with reported values and optimized the
      protocol to develop a simple, homogeneous, and sensitive binding assay in a 384
      well format. Finally, we assessed if this system could identify small peptides
      capable of inhibiting the OX40 receptor and ligand interaction. The results
      showed that the assay was able to detect such peptides and could be used to
      launch a high-throughput screening campaign for small molecules able to prevent
      OX40 receptor activation.

PMID- 14567780
TI  - Comparative study of membrane potential-sensitive fluorescent probes and their
      use in ion channel screening assays.
AB  - In this study, the authors compared and evaluated 4 membrane potential probes in
      the same cellular assay: the oxonol dye DiBAC(4)(3), the FLIPR membrane potential
      (FMP) dye (Molecular Devices), and 2 novel fluorescence resonance energy transfer
      (FRET) dye systems from PanVera [CC2-DMPE/DiSBAC(2)(3)] and Axiom
      [DiSBAC(1)(3)/DiSBAC(1)(5)]. The kinetic parameters of each membrane probe were
      investigated in RBL-2H3 cells expressing an endogenous inward rectifier potassium
      channel (IRK1). The FMP dye presented the highest signal over background ratio
      whereas the FRET dyes from PanVera gave the fastest response. The determination
      of IC(50) values for 8 different channel modulators indicated a good correlation
      between the 4 membrane probe systems. The compound-dye interaction was evaluated
      in the presence of compounds at 10 muM and clearly indicated no effect on the FMP
      or the PanVera donor dye, whereas some major interference with the oxonol probes
      was observed. Using a cell permeabilization assay in the presence of gramicidin,
      the authors concluded that the FRET dyes from PanVera and the FMP dye are unable
      to measure the gramicidin-induced cell membrane hyperpolarizations. The 4 dye
      systems were investigated under high-throughput screening (HTS) conditions, and
      their respective Z' parameter was determined. The characteristics of each dye
      system and its potential use in HTS assays is discussed.

PMID- 14567781
TI  - A high-throughput method for enzyme kinetic studies.
AB  - A simple and flexible setup for conducting drug metabolism studies is described
      in this report. A heating block was designed for the Multimek liquid handler
      platform for incubation of multiple samples at 37 degrees C in a 96-well format.
      This setup enables the rapid performance of drug metabolism experiments on a
      large number of samples. In this report, the authors present the validation of
      the system by 1) showing reproducible and consistent determination of the in
      vitro half-life of midazolam in every well across the entire plate and 2)
      determination of metabolic parameter values of midazolam, testosterone,
      diclofenac, warfarin, and dextromethorphan and inhibition parameter values of
      quinidine and ketoconazole, all comparable to literature values. In addition, the
      authors demonstrate the application of the setup to determining the metabolic
      stability of a set of proprietary compounds, the inhibition of activity of
      cytochrome P450 (CYP) enzymes, and the conduct of a single combination experiment
      that can simultaneously determine the metabolic stability and CYP inhibition
      activity. Overall, the system represents a simple, high-throughput and useful
      tool for drug metabolism screening in drug discovery.

PMID- 14567782
TI  - Development of a screening assay to measure the loss of antibacterial activity in
      the presence of proteins: its use in optimizing compound structure.
AB  - An assay quantifying the loss of antibacterial potency of compounds, originally
      identified via target-based screening, in the presence of increasing albumin
      concentration was developed and used as a technique to measure potential
      association of compounds with proteins unrelated to their molecular target.
      Minimum inhibitory concentrations (MICs) of test compounds were measured against
      Staphylococcus aureus strain ATCC 6538 in the presence of 0-12 muM bovine serum
      albumin (BSA). The linear regression coefficient r(2) for the correlation between
      MIC and BSA concentration was >/= 0.9 for 49 and > 0.5 for 62 out of a total of
      69 compounds tested. The slope of these correlations varied widely from < 1 to
      99, suggesting that the loss of potency due to a given concentration of BSA could
      vary from compound to compound due to wide variation in the apparent
      stoichiometry for protein-ligand association. Follow-up experiments using
      additional proteins and a fatty acid, oleic acid, showed that this compound:BSA
      association was not protein specific, but was likely driven by hydrophobicity.
      The method described in this report can be used to optimize compound design and
      minimize this undesirable effect.

PMID- 14567783
TI  - A high-throughput amenable colorimetric assay for enantioselective screening of
      nitrilase-producing microorganisms using pH sensitive indicators.
AB  - Based on the color change of an indicator due to the release of hydrogen ion from
      a nitrilase-catalyzed reaction, a rapid colorimetric method was established for
      the enantioselective screening of nitrilase-producing microorganisms. The
      formation of acids due to the nitrilase-mediated hydrolysis of nitriles causes a
      drop in the pH, which in turn results in a change of color of the solution
      (containing indicator) that can be observed visually. The buffer (0.01 M
      phosphate, pH 7.2) and indicator (Bromothymol blue, 0.01%) were selected in such
      a way that both have the same affinity for the released protons. The
      enantioselectivity of nitrilases was estimated by comparing the hydrolysis of (R)
      mandelonitrile with that of racemate under the same conditions. The method was
      used to screen a library of nitrilase-producing microorganisms, isolated in the
      authors' laboratory for their ability to enantioselectively hydrolyze
      mandelonitrile to mandelic acid, an important chiral building block.

PMID- 14567784
TI  - A simple technique for reducing edge effect in cell-based assays.
AB  - Several factors are known to increase the noise and variability of cell-based
      assays used for high-throughput screening. In particular, edge effects can result
      in an unacceptably high plate rejection rate in screening runs. In an effort to
      minimize these variations, the authors analyzed a number of factors that could
      contribute to edge effects in cell-based assays. They found that pre-incubation
      of newly seeded plates in ambient conditions (air at room temperature) resulted
      in even distribution of the cells in each well. In contrast, when newly seeded
      plates were placed directly in the CO(2) incubator, an uneven distribution of
      cells occurred in wells around the plate periphery, resulting in increased edge
      effect. Here, the authors show that the simple, inexpensive approach of
      incubating newly seeded plates at room temperature before placing them in a 37
      degrees C CO(2) incubator yields a significant reduction in edge effect.

PMID- 14567789
TI  - Screening in academe: a perspective on implementation of university-based small
      molecule screening.

PMID- 14567785
TI  - Evaluation of FLIPR Calcium 3 Assay Kit--a new no-wash fluorescence calcium
      indicator reagent.
AB  - We have evaluated the FLIPR Calcium 3 Assay Kit (Calcium 3), a new no-wash
      fluorescence calcium indicator dye reagent, for the measurement of agonist
      stimulated calcium signaling in cells expressing the serotonin 2C (5-HT(2C)),
      metabotropic glutamate receptor 5 (mGluR5) and the vasopressin 2 (V2) G-protein
      coupled receptors. Calcium 3 yielded equivalent (5-HT(2C)) or superior (mGluR5
      and V2) sensitivity to FLUO-4 as indexed by the change in fluorescence counts
      following agonist application. Assay variability, indexed by CV, using Calcium 3
      or FLUO-4 was equivalent with 5-HT(2C) receptor responses although CVs were
      reduced using Calcium 3 in the examples of the mGluR5 and V2 receptors. Receptor
      pharmacologies based on agonist EC(50) values were identical when either Calcium
      3 or FLUO-4 were utilized. Our results validate Calcium 3 as a compelling
      alternative to FLUO-4 in the choice of fluorescent dye reagent for studying G
      protein-coupled receptors, providing the advantage of a homogenous, no-wash assay
      format.

PMID- 14567790
TI  - Comparison of assay technologies for a nuclear receptor assay screen reveals
      differences in the sets of identified functional antagonists.
AB  - Many assay technologies currently exist to develop high-throughput screening
      assays, and the number of choices continues to increase. Results from a previous
      study comparing assay technologies in our laboratory do not support the common
      assumption that the same hits would be found regardless of which assay technology
      is used. To extend this investigation, a nuclear receptor antagonist assay was
      developed using 3 assay formats: AlphaScreen, time-resolved fluorescence (TRF),
      and time-resolved fluorescence resonance energy transfer (TR-FRET). Compounds (
      approximately 42000) from the Novartis library were evaluated in all 3 assay
      formats. A total of 128 compounds were evaluated in dose-response experiments,
      and 109 compounds were confirmed active from all 3 formats. The AlphaScreen, TRF,
      and TR-FRET assay technologies identified 104, 23, and 57 active compounds,
      respectively, with only 18 compounds active in all 3 assay formats. A total of
      128 compounds were evaluated in a cell-based functional assay, and 35 compounds
      demonstrated activity in this cellular assay. Furthermore, 34, 11, and 16 hits
      that were originally identified in the dose-response experiment by AlphaScreen,
      TRF, and TR-FRET assay technologies, respectively, were functionally active. The
      results of the study indicated that AlphaScreen identified the greatest number of
      functional antagonists.

PMID- 14567791
TI  - Detecting spatial patterns in biological array experiments.
AB  - Chemical genetic screening and DNA and protein microarrays are among a number of
      increasingly important and widely used biological research tools that involve
      large numbers of parallel experiments arranged in a spatial array. It is often
      difficult to ensure that uniform experimental conditions are present throughout
      the entire array, and as a result, one often observes systematic spatially
      correlated errors, especially when array experiments are performed using robots.
      Here, the authors apply techniques based on the discrete Fourier transform to
      identify and quantify spatially correlated errors superimposed on a spatially
      random background. They demonstrate that these techniques are effective in
      identifying common spatially systematic errors in high-throughput 384-well
      microplate assay data. In addition, the authors employ a statistical test to
      allow for automatic detection of such errors. Software tools for using this
      approach are provided.

PMID- 14567792
TI  - Data concordance from a comparison between filter binding and fluorescence
      polarization assay formats for identification of ROCK-II inhibitors.
AB  - The Rho-associated coiled-coil-containing protein serine/threonine kinases ROCK-I
      and ROCK-II are thought to play a major role in cytoskeletal dynamics by serving
      as downstream effectors of the Rho/Rac family of cytokine- and growth factor
      activated small GTPases. As such, the ROCK family members are attractive
      intervention targets for a variety of pathologies, including cancer and
      cardiovascular disease. The authors developed a high-throughput screen to
      identify ROCK-II inhibitors and report results from a direct comparison of 2
      screening campaigns for ROCK-II inhibitors using fluorescence polarization (FP)
      and filter binding (FB). Screening protocols to identify inhibitors of ROCK-II
      were developed in FB and FP formats under similar assay and kinetic conditions. A
      30,000-member compound library was screened using FB ((33)P) and FP detection
      systems, and compounds that were active in either assay were retested in 5-point
      curve confirmation assays. Analysis of these data showed an approximate 95%
      agreement of compounds identified as active in both assay formats. Also, compound
      potency determinations from FB and FP had a high degree of correlation and were
      considered equivalent. These data suggest that the assay methodology has little
      impact on the quality and productivity of the screen, provided that the assays
      are developed to standardize kinetic conditions.

PMID- 14567793
TI  - Miniaturization of fluorescence polarization receptor-binding assays using CyDye
      labeled ligands.
AB  - Fluorescence polarization (FP) is an established technique for the study of
      biological interactions and is frequently used in the high-throughput screening
      (HTS) of potential new drug targets. This work describes the miniaturization of
      FP receptor assays to 1536-well formats for use in HTS. The FP assays were
      initially developed in 384-well microplates using CyDye-labeled nonpeptide and
      peptide ligands. Receptor expression levels varied from approximately 1 to 10
      pmols receptor per mg protein, and ligand concentrations were in the 0.5- to 1.0
      nM range. The FP assays were successfully miniaturized to 1536-well formats using
      Cy3B-labeled ligands, significantly reducing reagent consumption, particularly
      the receptor source, without compromising assay reliability. Z' factor values
      determined for the FP receptor assays in both 384- and 1536-well formats were
      found to be > 0.5, indicating the assays to be robust, reliable, and suitable for
      HTS purposes.

PMID- 14567794
TI  - Screening of natural products extracts for the presence of phosphodiesterase
      inhibitors using liquid chromatography coupled online to parallel biochemical
      detection and chemical characterization.
AB  - The ability to rapidly identify active compounds in a complex mixture (e.g.,
      natural products extract) is still one of the major problems in natural products
      screening programs. An elegant way to overcome this problem is to separate the
      complex mixture by gradient liquid chromatography followed by online biochemical
      detection parallel with chemical characterization, referred to as high-resolution
      screening (HRS). To find and identify phosphodiesterase (PDE) inhibitors in
      natural products extracts using the HRS technology, the authors developed a
      continuous-flow PDE enzymatic assay. The suitability of the continuous-flow PDE
      enzymatic assay for natural products screening was demonstrated. After
      optimization of the continuous-flow PDE assay, the limit of detection for 3
      isobutyl-1-methyl-xanthine (IBMX) was 1 muM, with a dynamic range from 1 to 100
      muM IBMX. The applicability of the HRS technology for the detection of PDE
      inhibitors in natural products extracts was demonstrated by the analysis of a
      plant extract spiked with 2 naturally occurring PDE inhibitors. The plant extract
      was analyzed with 2 assay lines in parallel, enabling background fluorescence
      correction of the sample. The simultaneous quantification of the active compounds
      using evaporative light-scattering detection allowed the estimation of the IC(50)
      value of the active compounds directly in the crude extract.

PMID- 14567795
TI  - A cell-based radioligand binding assay for farnesyl: protein transferase
      inhibitors.
AB  - Farnesyl:protein transferase (FPTase) catalyzes the covalent addition of the
      isoprenyl moiety of farnesylpyrophosphate to the C-terminus of the Ras
      oncoprotein and other cellular proteins. Inhibitors of FPTase (FTIs) have been
      developed as potential anticancer agents, and several compounds have been
      evaluated in clinical trials. To facilitate the identification of cell-active
      FTIs with high potency, the authors developed a method that uses a radiolabeled
      FTI that serves as a ligand in competitive displacement assays. Using high
      affinity [(3)H]-labeled or [(125)I]-labeled FTI radioligands, they show that
      specific binding to FPTase can be detected in intact cells. Binding of these
      labeled FTI radioligands can be competed with a variety of structurally diverse
      FTIs, and the authors show that inhibition of FTI radioligand binding correlates
      well with inhibition of FPTase substrate prenylation in cells. This method
      provides a rapid and quantitative means of assessing FTI potency in cells and is
      useful for guiding the discovery of potent, novel inhibitors of FPTase. Similar
      methods could be employed in the optimization of inhibitors for other
      intracellular drug targets.

PMID- 14567796
TI  - Validation of a cell-based screen for insulin receptor modulators by
      quantification of insulin receptor phosphorylation.
AB  - Stimulation of a cell with insulin initiates a signal transduction cascade that
      results in cellular activities that include phosphorylation of the receptor
      itself. Measurement of the degree of phosphorylation can serve as a marker for
      receptor activation. Receptor phosphorylation has been measured using Western
      blot analysis, which is very low throughput and not easily quantifiable. The goal
      of this project was to develop a cell-based assay to measure receptor
      phosphorylation in high throughput. This report describes a cell-based assay for
      insulin receptor phosphorylation that is robust and amenable to high-volume
      screening in a microwell format.

PMID- 14567797
TI  - A widely applicable, high-throughput TR-FRET assay for the measurement of kinase
      autophosphorylation: VEGFR-2 as a prototype.
AB  - Homogeneous time-resolved fluorescence resonance energy transfer (TR-FRET) assays
      represent a highly sensitive and robust high-throughput screening (HTS) method
      for the quantification of kinase activity. Traditional TR-FRET kinase assays
      detect the phosphorylation of an exogenous substrate. The authors describe the
      development and optimization of a TR-FRET technique that measures the
      autophosphorylation of vascular endothelial growth factor receptor 2 (VEGFR-2)
      kinase and extend its applicability to a variety of other kinases. The VEGFR-2
      assay demonstrated dose-dependent inhibition by compounds known to modulate the
      catalytic activity of this receptor. In addition, kinetic analysis of a
      previously characterized VEGFR-2 inhibitor was performed using the method, and
      results were consistent with those obtained using a different assay format.
      Because of the known involvement of VEGFR-2 in angiogenesis, this assay should
      facilitate HTS for antiangiogenic agents. In addition, this general technique
      should have utility for the screening for inhibitors of kinases as potential
      therapeutic agents for many other disease indications.

PMID- 14567798
TI  - Optimization of a higher throughput microsomal stability screening assay for
      profiling drug discovery candidates.
AB  - Metabolic stability plays an important role in the success of drug candidates.
      First-pass metabolism is one of the major causes of poor oral bioavailability and
      short half-life. Traditionally, metabolic stability was evaluated at a later
      stage of drug discovery and required laborious manual manipulations. With the
      advance of high-throughput screening, combinatorial chemistry, and early
      profiling of drug-like properties, automated and rapid stability assays are
      needed to meet the increasing demand of throughput, speed, and reproducibility at
      earlier stages of drug discovery. The authors describe optimization of a simple,
      robust, high-throughput microsomal stability assay developed in a 96-well format.
      The assay consists of 2 automated components: robotic sample preparation for
      incubation and cleanup and rapid liquid chromatography/mass spectrometry/mass
      spectrometry (LC/MS/MS) analysis to determine percent remaining of the parent
      compound. The reagent solutions and procedural steps were optimized for
      automation. Variables affecting assay results were investigated. The variability
      introduced by microsome preparations from different sources (various vendors and
      batches) was studied and indicates the need for careful control. Quality control
      and normalization of the stability results are critical when applying the
      screening data, generated at different times or research sites, to discovery
      projects.

PMID- 14567802
TI  - Twenty-one years inside the uterus.

PMID- 14567799
TI  - Development of a novel high-throughput surrogate assay to measure HIV
      envelope/CCR5/CD4-mediated viral/cell fusion using BacMam baculovirus technology.
AB  - The initial event by which M-tropic HIV strains gain access to cells is via
      interaction of the viral envelope protein gp120 with the host cell CCR5
      coreceptor and CD4. Inhibition of this event reduces viral fusion and entry into
      cells in vitro. The authors have employed BacMam baculovirus-mediated gene
      transduction to develop a cell/cell fusion assay that mimics the HIV viral/cell
      fusion process and allows high-throughput quantification of this fusion event.
      The assay design uses human osteosarcoma (HOS) cells stably transfected with
      cDNAs expressing CCR5, CD4, and long terminal repeat (LTR)-luciferase as the
      recipient host cell. An HEK-293 cell line transduced with BacMam viral constructs
      to express the viral proteins gp120, gp41, tat, and rev represents the virus.
      Interaction of gp120 with CCR5/CD4 results in the fusion of the 2 cells and
      transfer of tat to the HOS cell cytosol; tat, in turn, binds to the LTR region on
      the luciferase reporter and activates transcription, resulting in an increase in
      cellular luciferase activity. In conclusion, the cell/cell fusion assay developed
      has been demonstrated to be a robust and reproducible high-throughput surrogate
      assay that can be used to assess the effects of compounds on gp120/CCR5/CD4
      mediated viral fusion into host cells.

PMID- 14567803
TI  - Comparative, double-blind, randomized, placebo-controlled trial of
      intraperitoneal of bupivacaine and lidocaine for pain control after diagnostic
      laparoscopy.
AB  - STUDY OBJECTIVE: To compare the effect of intraperitoneal bupivacaine and
      lidocaine on reducing pain after diagnostic laparoscopy. DESIGN: Randomized,
      double-blind, placebo-controlled study (Canadian Task Force classification I).
      SETTING: University teaching hospital. PATIENTS: One hundred thirty-four women
      with unexplained infertility. INTERVENTION: Diagnostic laparoscopy with
      intraperitoneal administration of bupivacaine or lidocaine. MEASUREMENTS AND MAIN
      RESULTS: Patients were randomized into one of four groups. In group A, at the end
      of laparoscopy 0.125% bupivacaine 30 ml was instilled into the pelvic cavity and
      the same dose was instilled over the diaphragmatic vault. Groups B and C received
      the same volume of 5% lidocaine and normal saline, respectively. Group D received
      no intraperitoneal agent. The verbal pain scale questionnaire was used to assess
      postoperative pain. Pain scores 2 and 24 hours postoperatively were significantly
      lower for group A than for groups B and C (p = 0.0001). Scores in group B were
      also significantly lower than those in groups C and D (p = 0.0001). Women in
      group A required less additional analgesia than those in the other groups.
      CONCLUSION: Compared with lidocaine and placebo, intraperitoneal bupivacaine
      significantly decreased postoperative pain, and this effect was long lasting.

PMID- 14567804
TI  - GnRH agonist treatment before total laparoscopic hysterectomy for large uteri.
AB  - STUDY OBJECTIVE: To evaluate whether uterine shrinkage induced by gonadotropin
      releasing hormone (GnRH) agonists in women with a large uterus (>14 wks) may
      facilitate total laparoscopic hysterectomy. DESIGN: Randomized, prospective study
      (Canadian Task Force classification I). SETTING: University-affiliated hospital.
      PATIENTS: Sixty-two women with symptomatic uterine myomas (size 16-20 wks).
      INTERVENTIONS: Total laparoscopic hysterectomy for benign pathology. MEASUREMENTS
      AND MAIN RESULTS: Before surgery, women were assigned, at a ratio of 1:1 by
      random selection, to receive injections of triptorelin depot 11.25 mg 3 months
      before surgery (group A) or no treatment (group B). Uterine volume, mean
      operating time, uterine weight, drop in hemoglobin, intraoperative complications,
      conversions to laparotomy, and hospital stay were recorded. Triptorelin decreased
      uterine volume, calculated by ultrasonography, by 26.5% in group A, whereas the
      volume remained unchanged in group B. Statistical differences were found between
      groups concerning uterine weight, operating time, and drop in hemoglobin level.
      Three patients in group B were converted to laparotomy because of uterine size.
      CONCLUSION: In women with a large uterus, a 3-month preoperative course of GnRH
      may facilitate laparoscopic hysterectomy, decreasing uterine size, operating
      time, and blood loss.

PMID- 14567805
TI  - Transvaginal three-dimensional ultrasonography combined with serum CA 125 level
      for the diagnosis of pelvic adhesions before laparoscopic surgery.
AB  - STUDY OBJECTIVE: To investigate the role of transvaginal three-dimensional
      ultrasonography combined with serum CA 125 level in diagnosing pelvic adhesions
      before scheduled laparoscopic surgery. DESIGN: Prospective study (Canadian Task
      Force classification II-1). SETTING: Tertiary care academic hospital. PATIENTS:
      Fifty-nine women with an adnexal mass diagnosed by two-dimensional transvaginal
      ultrasonography. INTERVENTION: Preoperative transvaginal three-dimensional
      ultrasonography and serum CA 125 level, followed by laparoscopy or laparotomy.
      MEASUREMENTS AND MAIN RESULTS: Pelvic adhesions were correctly identified by
      transvaginal three-dimensional ultrasonography in 26 of 32 women in whom the
      lesions were confirmed at laparoscopy or laparotomy. Mean serum CA125 level in
      women with adhesions was 70 +/- 73.7 U/ml, which was significantly higher than
      that in women without adhesions (24 +/- 16.16 U/ml, p = 0.004). The sensitivity
      of combined transvaginal three-dimensional ultrasonography and serum CA 125 level
      was 90%, specificity was 100%, positive predictive value was 100%, and negative
      predictive value was 89%. The two methods showed strong agreement with surgical
      results (kappa = 0.889). Eight scheduled laparoscopies (13.6%) were converted to
      laparotomy due to severe adhesions. One patient (1.7%) experienced colon injury
      during laparoscopic adhesiolysis. CONCLUSION: Transvaginal three-dimensional
      ultrasonography combined with serum CA 125 level is sensitive in detecting pelvic
      adhesions before laparoscopic surgery. Patients with suspected severe pelvic
      adhesions should have preoperative bowel preparation to reduce the risk of
      intraoperative injury.

PMID- 14567806
TI  - Laparoscopic two-team slings for women with stress urinary incontinence.
AB  - STUDY OBJECTIVE: To review long-term success and complication rates of
      laparoscopic two-team sling procedures in women with stress urinary incontinence
      or mixed incontinence confirmed by urodynamic testing and cystoscopy. DESIGN:
      Prospective study (Canadian Task Force classification II-2). SETTING: Tertiary
      urogynecology unit at a university-affiliated teaching hospital. PATIENTS: One
      hundred seventy-five women. INTERVENTIONS: Laparoscopic two-team sling procedure.
      MEASUREMENTS AND MAIN RESULTS: The extraperitoneal approach to the space of
      Retzius was accomplished using a balloon device, and the intraperitoneal approach
      involved a transverse incision through the anterior parietal peritoneum 6 cm
      above the symphysis. A 1.5- to 2.0-cm wide strip of polypropylene mesh was
      inserted through a vertical incision along the anterior vaginal wall, perforating
      the urogenital diaphragm under laparoscopic guidance. The mesh was sutured to
      Cooper's ligaments bilaterally with 0 polypropylene sutures. Mean operating time
      was 80.1 +/- 30.0 minutes, mean estimated blood loss was 160 +/- 146 ml, and mean
      hospital stay was 2.4 +/- 1.2 days. Patients were followed at 6 weeks, 6 months,
      1 year, and yearly (mean 17.8 mo, range 1-5 yrs). CONCLUSION: Laparoscopic two
      team sling procedures can be performed safely in women with recurrent stress
      incontinence and those with risk factors for failure of retropubic urethropexy.
      Long-term success rates are excellent (91.1%) with few complications.

PMID- 14567807
TI  - Initial feasibility study of a sprayable hydrogel adhesion barrier system in
      patients undergoing laparoscopic ovarian surgery.
AB  - STUDY OBJECTIVE: To assess the safety and effectiveness of SprayGel as a barrier
      to reduce the frequency of adhesion formation and reformation after ovarian
      surgery, and to determine the feasibility of the study design for a larger,
      multicenter pivotal trial. DESIGN: Prospective, randomized, internally controlled
      trial (Canadian Task Force classification I). SETTING: Two metropolitan, academic
      affiliated, nonprofit hospitals. PATIENTS: Fourteen women. INTERVENTION:
      Bilateral adnexal surgery. MEASUREMENTS AND MAIN RESULTS: On completion of
      surgery, one adnexa was randomized to receive optimal surgical treatment plus
      application of the adhesion barrier, and the contralateral one to receive optimal
      surgical treatment alone. Patients returned in 3 to 16 weeks for second-look
      laparoscopy. All initial and second-look procedures were videotaped and reviewed
      by a blinded surgeon reviewer, and assessed for frequency, extent, and severity
      of adhesions. The frequency and extent of adhesion formation at second-look
      laparoscopy were statistically reduced on treatment sides compared with control
      sides (71% reduction in frequency, p = 0.0488; 69% reduction in extent, p =
      0.0494). Adhesion severity score was reduced by 43% on the treatment side.
      SprayGel was associated with no adverse effects and was applied successfully in
      all patients. CONCLUSION: This material shows great promise in preventing
      postoperative adhesion formation in a population of patients greatly in need of
      such an adjunct. These findings warrant a larger, pivotal, multicenter study to
      evaluate SprayGel further.

PMID- 14567808
TI  - Prospective clinical trial of SprayGel as a barrier to adhesion formation: an
      interim analysis.
AB  - STUDY OBJECTIVE: To evaluate SprayGel, a new sprayable adhesion barrier developed
      for laparoscopic and open pelvic and abdominal surgical procedures. DESIGN:
      Prospective, randomized, controlled, multicenter trial (Canadian Task Force
      classification I). SETTING: University clinic and private clinic. PATIENTS: Forty
      five women, 24 randomized to treatment and 21 to control group. INTERVENTIONS:
      Open or laparoscopic myomectomy with and without application of SprayGel,
      followed by second-look laparoscopy (SLL) to evaluate postoperative adhesions.
      MEASUREMENTS AND MAIN RESULTS: Application of SprayGel was fast and easy. On
      average, 10 weeks after surgery, 18 treated patients (75%) and 13 (61.9%)
      controls had SLL. That procedure showed 5 (27.8%) of 18 treatment patients to be
      adhesion free versus 1 (7.7%) of 13 controls (p = 0.163). Patients randomized to
      SprayGel were 3.6 times more likely to be adhesion free than controls. Mean
      tenacity scores were significantly lower than in controls (0.5 vs. 1.7), a
      difference of 0.9 (95% CI 0.3, 1.5, p = 0.003) or 47% (95% CI 17%, 77%) less.
      Mean adhesion area was reduced in the treatment group (4.1 vs. 5.6) but not
      significant (p = 0.6747, 95% CI-5.4, 8.4). No adverse events regarding
      application of SprayGel were seen. CONCLUSION: SprayGel was effective in reducing
      postoperative adhesion severity, and showed a trend toward reducing frequency and
      extent of adhesions after laparoscopic and open myomectomy. Further studies are
      necessary to confirm the promising results of this interim analysis.

PMID- 14567809
TI  - Feasibility and safety of total laparoscopic radical hysterectomy.
AB  - STUDY OBJECTIVE: To evaluate feasibility and morbidity of a total laparoscopic
      radical hysterectomy (TLRH). DESIGN: Retrospective chart review (Canadian Task
      Force classification II-3). SETTING: Gynecologic cancer center. PATIENTS: Fifty
      five women with cervical (39), endometrial (8), vaginal (2), or recurrent colon
      cancer (1), or severe pelvic endometriosis (5) followed for 3 years.
      INTERVENTION: TLRH in 55 women, converted to laparotomy in 3 (5.5%). MEASUREMENTS
      AND MAIN RESULTS: Feasibility, safety, patterns of recurrence, and survival were
      assessed. Estimated blood loss was 200 ml (range 50-2000 ml), median total
      operating time was 210 minutes, and median hospital stay was 5 days.
      Intraoperative complications were three vascular injuries and one obturator nerve
      palsy, all of which occurred in the first half of the series. Early postoperative
      morbidity included deep vein thrombosis, pulmonary embolism, bladder infection
      and dysfunction, and vaginal fistula. These events occurred less frequently in
      the second half of the series. Late postoperative morbidity consisted of
      lymphedema, pelvic abscess and lymphocyst formation, pelvic cellulitis,
      hyperesthesia of the leg, and small bowel obstruction. The only fatality was a
      patient who developed a pulmonary embolus on postoperative day 3. Median follow
      up was 36.5 months. Of 39 women with cervical cancer, 34 were alive and disease
      free at their last visit. No case of port site metastasis occurred during follow
      up. CONCLUSION: TLRH carries acceptably low morbidity that can be reduced with
      experience with the technique.

PMID- 14567810
TI  - Small intestine injury in laparoscopic-assisted vaginal hysterectomy.
AB  - STUDY OBJECTIVE: To review laparoscopic-assisted vaginal hysterectomy (LAVH)
      cases for instances of small intestine injury. DESIGN: Retrospective review
      (Canadian Task Force Classification II-2). SETTING: Tertiary care university
      hospital. PATIENTS: Two thousand six hundred eighty-two women. INTERVENTION:
      LAVH. MEASUREMENTS AND MAIN RESULTS: Indications for hysterectomy were myomata
      uteri, adenomyosis, intractable menorrhagia, endometriosis, severe pelvic
      adhesions, cervical intraepithelial neoplasia, endometrial polyps, and
      hyperplasia. Small bowel injuries occurred in five women (1.9/1000), one (20%) of
      which was recognized postoperatively. Thermal injuries occurred in two patients,
      trocar injuries in two, and a dissection wound in one. Two-layer closure was
      performed for three patients, and partial resection with reanastomosis for two.
      All patients were discharged without sequelae. CONCLUSION: Small bowel injury
      during LAVH is not common. It may have unusual characteristics and devastating
      consequences if not recognized and treated promptly.

PMID- 14567811
TI  - The effect of physician experience on costs and clinical outcomes of laparoscopic
      assisted vaginal hysterectomy: a multivariate analysis.
AB  - STUDY OBJECTIVE: To evaluate whether or not a physician's experience has an
      effect on costs and clinical outcomes of an implemented clinical pathway for
      laparoscopic-assisted vaginal hysterectomy (LAVH). DESIGN: Retrospective study
      (Canadian Task Force classification II-2). SETTING: University hospital.
      PATIENTS: One hundred twenty women. INTERVENTION: LAVHs, 84 performed by senior
      physicians and 36 by junior physicians. MEASUREMENTS AND MAIN RESULTS: According
      to results of multiple linear regression analysis, after controlling for other
      independent variables, senior attending physicians, each with over 6 years of
      experience, managed to reduce all costs related to LAVH, operating time, and
      length of stay. Logistic regression analysis revealed no differences in the
      occurrence of intravenous fluid injection, antibiotic injection more than 2 days
      after surgery, and complications between physicians with and those without
      experience. Neither group had blood transfusions, patient mortality, or
      readmissions within 2 weeks of discharge. CONCLUSION: Physician experience
      reduces medical costs and maintains the quality of care in LAVH. We suggest
      regular training courses for less-experienced physicians in order to contain
      costs and maintain quality of care under the quota case-payment system.

PMID- 14567812
TI  - Location of adenomyosis in total hysterectomy specimens.
AB  - STUDY OBJECTIVE: To determine the location of adenomyosis in hysterectomy
      specimens and estimate a risk of leaving the disease in patients undergoing
      supracervical hysterectomy. DESIGN: Retrospective cohort study (Canadian Task
      Force classification II-2). SETTING: University teaching hospital. SUBJECTS:
      Total hysterectomy specimens from 32 women. MEASUREMENTS AND MAIN RESULTS: Each
      patient had six slides representing anterior and posterior cuts of the uterus at
      the cervix, lower uterine segment, and fundus. Analyzing the six groups
      separately, no significant difference was seen in the number of nests between
      anterior and posterior slides at the same uterine level. A substantial difference
      was noted between each site and all other sites on other uterine levels. Grouping
      the anterior and posterior together, a significant difference was found in the
      number of nests between all levels (p <0.001). Evaluating only for presence of
      disease, no significant difference was found between the anterior and posterior
      of each level, a significant difference was seen between each site and sites at
      all other levels, and a difference was noted among all levels when the anterior
      and posterior were grouped (all p <0.001). CONCLUSION: Adenomyosis has a
      significant propensity to be present in the uterine fundus but it is extremely
      rare in the cervix. Supracervical hysterectomy for adenomyosis is unlikely to
      leave disease in the patient as long as the entire lower uterine segment is
      excised.

PMID- 14567813
TI  - Laparoscopic transabdominal cervicoisthmic cerclage during pregnancy.
AB  - STUDY OBJECTIVE: To evaluate and describe our experience in the management of
      recurrent second-trimester miscarriage and preterm delivery by laparoscopic
      transabdominal cervicoisthmic cerclage (LTCC), after failure of transvaginal
      cervical cerclage. DESIGN: Retrospective review (Canadian Task Force
      classification III). SETTING: Tertiary care teaching hospital. PATIENTS: Twenty
      women in whom it was not technically possible to perform transvaginal cerclage.
      INTERVENTION: LTCC. MEASUREMENTS AND MAIN RESULTS: Mean operating time was 55
      minutes (range 40-75 min). There were no operative or immediate postoperative
      complications. Mean gestational age at the time of cerclage placement was 12.1
      weeks (range 11-14 wks). Nineteen women successfully delivered 21 live babies (2
      sets of twins; live birth rate 95%). One loss occurred after rupture of membrane
      at 19 weeks' after cerclage. CONCLUSION: LTCC during pregnancy can be safe and
      effective treatment for well-selected patients with cervical incompetence, and
      eliminates the need for open laparotomy.

PMID- 14567814
TI  - Hysterosalpingo-contrast sonography compared with hysterosalpingography and
      laparoscopic dye pertubation to evaluate tubal patency.
AB  - STUDY OBJECTIVE: To evaluate the advantages and accuracy of hysterosalpingo
      contrast sonography (HyCoSy) in assessing tubal patency compared with
      hysterosalpingogram (HSG) and laparoscopic dye pertubation. DESIGN: Prospective
      study (Canadian Task Force classification II-2). SETTING: Obstetrics and
      Gynecology Department, University of Rome Tor Vergata. PATIENTS: Twenty-three
      women with at least 1 year of infertility, and 15 women with a history of chronic
      pelvic pain, suspected endometriosis, or pelvic inflammatory disease (PID), or
      with sonographic markers of adhesions. INTERVENTIONS: HyCoSy, HSG, and
      laparoscopic dye pertubation. MEASUREMENTS AND MAIN RESULTS: All patients
      underwent HyCoSy during the proliferative phase using air with saline as contrast
      medium, and HSG within 1 month of HyCoSy. Laparoscopy and dye pertubation were
      performed only in women with chronic pelvic pain, suspected endometriosis, PID,
      and sonographic markers of adhesions. In women undergoing all three procedures,
      HSG and HyCoSy had the same high concordance as laparoscopy, 86.7% and 86.7%,
      respectively. Three women in the infertility group became pregnant immediately
      after HyCoSy and dropped out of the study. In one woman, HyCoSy could not be
      performed because of cervical stenosis. Considering the total number of tubes
      (67), concordance between HyCoSy and HSG was 89.6%. CONCLUSION: Transvaginal
      HyCoSy using a combination of air and saline appears to be an inexpensive, fast,
      and well-tolerated method of determining tubal patency. One of the most important
      advantages of this technique is, in our opinion, the possibility of obtaining
      information on tubal status and the uterine cavity at the same time as
      conventional ultrasound scan is performed.

PMID- 14567815
TI  - Laparoscopic repair of ureteral injuries.
AB  - STUDY OBJECTIVES: To evaluate the laparoscopic approach for repairing ureteral
      injuries, and assess the effect of ureteral dissection (ureterolysis) on tissue
      healing. DESIGN: Randomized animal study (Canadian Task Force classification I).
      SETTING: Biological Resources Unit, Cleveland Clinic Foundation. SUBJECTS: Ten
      pigs. INTERVENTION: In all animals, the pelvic segment of the right ureter was
      completely dissected off the pelvic sidewall and peritoneum. In group A, both
      pelvic ureters were divided with scissors and repaired over a stent; in group B
      the ureters were coagulated and anastomosis was performed after resection of the
      necrotic segment. Laparoscopic intracorporeal suturing techniques were used for
      end-to-end ureteral anastomosis. MEASUREMENTS AND MAIN RESULTS: All animals
      survived without complications. Ureteral stents were removed 4 weeks after
      repair. Creatinine level and retrograde pyelogram performed before injury and 12
      weeks after repair were compared. At necropsy anastomoses were evaluated for
      leak, pressure flow studies, and histopathology. All anastomoses were patent with
      no leak. Although serum creatinine level increased significantly after repair (p
      = 0.001), this increase never reached levels found in renal failure, and all
      animals continued to do well and have good appetite (mean increase in body weight
      20.3 +/- 6.2 kg). Mild hydronephrosis was diagnosed in three kidneys, all on the
      right side. Mild ureteral dilatation occurred bilaterally; it was significant on
      the right side (3.8 +/- 3.8 mm, p = 0.05) but not on the left (1.7 +/- 2 mm, p =
      0.3). Results of pressure flow studies did not reveal significant obstruction at
      anastomoses. Healing around the dissected right ureter was marked with dense
      fibrosis, adhesions, and scar formation. On histopathology the right ureter
      showed more urothelial abnormalities than the left, with marked fibrosis and
      sclerosis in the muscularis and adventitial layers. CONCLUSION: Ureterolysis may
      interfere with the healing process of ureteral injuries by increasing fibrosis
      and adventitial scarring. Laparoscopic repair of these injuries is feasible and
      safe.

PMID- 14567816
TI  - Staging of pelvic endometriosis: role of sonographic appearance in determining
      extension of disease and modulating surgical approach.
AB  - STUDY OBJECTIVE: To estimate whether laparoscopic staging of endometriosis can be
      predicted by ultrasound findings. DESIGN: Prospective study (Canadian Task Force
      classification II-2). SETTING: Obstetrics and Gynecology Department, University
      of Rome Tor Vergata. PATIENTS: One hundred twenty-one women with histologically
      confirmed sonographic diagnosis of endometriomas. INTERVENTIONS: Ultrasonographic
      staging and laparoscopic assessment. MEASUREMENTS AND MAIN RESULTS: All patients
      underwent transvaginal and/or transrectal sonographic evaluation of ovarian
      endometriomas and other sonographic markers (anatomic sites and their relation to
      abdominovaginal palpation, adhesions, deep or infiltrating nodules) to stage the
      disease before surgery. These results were compared with laparoscopic staging.
      Concordance between methods was 83.5%. Specificity and sensitivity of
      ultrasonographic staging of stages 3 and 4 disease were 86% and 82% and 76% and
      91%, respectively. CONCLUSION: Ultrasonographic findings can predict pelvic
      extension and stage of endometriosis.

PMID- 14567817
TI  - Laparoscopic morcellator-related injuries.
AB  - STUDY OBJECTIVE: To identify and summarize all electric morcellator-related
      injuries published in the medical literature. DESIGN: Systematic review (Canadian
      Task Force classification II-2). SETTING: Databases. SUBJECTS: Articles on
      morcellator-related injuries published from 1992 through February 2002, plus
      additional sources of information. INTERVENTION: Search of MEDLINE and
      referencing of the FDA device report database. MEASUREMENTS AND MAIN RESULTS: We
      were unable to locate any references to morcellator-related visceral injuries in
      the medical literature. Of 17 cases identified from the FDA database, 3 were
      excluded based on the trivial nature of the event (e.g., instrument did not
      function). The remaining 14 visceral injuries were to small and large bowel (11),
      kidney (2), pancreas (1), and major vascular structures (3). Identification of
      the complication was immediate in 10 patients, but was not until 4 days
      postoperatively in 1 woman. Three patients died. No device manufacturer or
      surgical specialty was responsible for a preponderance of the injuries.
      CONCLUSION: These potentially fatal complications are unreported in the medical
      literature.

PMID- 14567818
TI  - Tension-free vaginal tape compared with laparoscopic Burch urethropexy.
AB  - STUDY OBJECTIVE: To compare laparoscopic Burch colposuspension and tension-free
      vaginal tape (TVT) procedure in women with genuine stress incontinence. DESIGN:
      Randomized clinical study (Canadian Task Force classification I). SETTING:
      Tertiary care university hospital. PATIENTS: Forty-six consecutive women.
      INTERVENTION: Laparoscopic Burch colposuspension (23) and TVT procedure (23).
      MEASUREMENTS AND MAIN RESULTS: Valsalva leak-point pressure increased after
      surgery in both groups, but TVT substantially decreased maximum urinary flow
      rate. Other urodynamic studies showed no statistical differences. The groups did
      not differ significantly with respect to intraoperative complications or
      objective and subjective cure rates. Operating time was significantly longer for
      laparoscopic Burch (p = 0.001), and three patients in that group required
      conversion to laparotomy. Length of hospital stay (p = 0.003) and duration of
      catheterization (p = 0.003) were shorter in the TVT group. CONCLUSION: TVT holds
      promise in women with genuine stress incontinence, with several advantages over
      laparoscopic Burch.

PMID- 14567819
TI  - A randomized trial of sublingual misoprostol for cervical priming before
      hysteroscopy.
AB  - STUDY OBJECTIVE: To evaluate the effects of sublingual misoprostol on cervical
      dilatation before hysteroscopy. DESIGN: Prospective randomized study (Canadian
      Task Force classification I). SETTING: University teaching center. PATIENTS:
      Forty nulliparous women who received injection of leuprolide acetate 4 weeks
      before hysteroscopy, of whom 20 were randomized to treatment with misoprostol and
      20 to placebo. INTERVENTION: Sublingual misoprostol 100 mug or placebo
      administered 12 hours before operative hysteroscopy. MEASUREMENTS AND MAIN
      RESULTS: Misoprostol was associated with mild abdominal cramps in four women
      (20%) and vaginal bleeding in another. No side effects were reported among women
      in the placebo group. There was no difference in baseline diameter of the
      cervical opening between the misoprostol group (4.0 +/- 0.1 mm) and the control
      group (4.2 +/- 0.2 mm). Time to dilate cervix up to 9 mm was also not
      significantly different (misoprostol 48.4 +/- 9.2 sec, placebo 37.7 +/- 4.1 sec).
      We found no difference in degree of difficulty dilating the cervix between
      groups. Cervical tear occurred in one patient in the misoprostol group.
      CONCLUSION: Sublingual misoprostol 100 mug does not facilitate cervical
      dilatation before hysteroscopy. This may be related to leuprolide's
      hypoestrogenic effect.

PMID- 14567820
TI  - Comparison of hysteroscopic and hysterectomy findings to assess the diagnostic
      accuracy of office hysteroscopy in tamoxifen-treated patients with breast cancer.
AB  - STUDY OBJECTIVE: To assess the diagnostic accuracy of office hysteroscopy by
      comparing hysteroscopic findings with histologic findings on hysterectomy
      specimens in postmenopausal women with breast cancer treated with tamoxifen.
      DESIGN: Retrospective clinical study (Canadian Task Force classification II-2).
      SETTING: University-affiliated hospital. PATIENTS: Thirty-three women.
      INTERVENTION: Record review. MEASUREMENTS AND MAIN RESULTS: Compared with
      histologic diagnoses of uteri, hysteroscopic findings showed diagnostic
      sensitivity of 97%, specificity of 100%, positive predictive value of 100% and
      negative predictive value of 96%. The diagnostic accuracy of hysteroscopy is the
      same in patients taking tamoxifen as in the general population. CONCLUSION:
      Hysteroscopy is a powerful method for diagnosing endometrial disease because it
      provides a direct view of the uterine cavity, reveals focal lesions, and enables
      targeted biopsies to be performed at the same time.

PMID- 14567821
TI  - Minihysteroscopy as routine diagnostic procedure in women with primary
      infertility.
AB  - STUDY OBJECTIVE: To evaluate the importance of routine minihysteroscopy in the
      diagnosis of primary infertility. DESIGN: Retrospective study (Canadian Task
      Force classification II-2). SETTING: Endoscopic center at a university hospital.
      PATIENTS: Three hundred seventy-nine patients with primary infertility.
      INTERVENTION: Diagnostic minihysteroscopy without anesthesia or sedation.
      MEASUREMENTS AND MAIN RESULTS: Hysteroscopy was normal in 337 patients (89.9%).
      In 38 patients (10.1%) an intrauterine pathology was found: 26 intrauterine
      adhesions, 12 cases of uterus subseptus. The procedure could not be completed in
      four women. CONCLUSION: Minihysteroscopy should become a routine diagnostic
      procedure in women with primary infertility, even those with no suspected
      intrauterine pathology or other risk factors.

PMID- 14567822
TI  - Tolerability and cardiovascular complications of outpatient diagnostic
      minihysteroscopy compared with conventional hysteroscopy.
AB  - STUDY OBJECTIVE: To assess acceptability and cardiovascular complications of
      hysteroscopy performed with minihysteroscopes compared with those performed with
      conventional hysteroscopes. DESIGN: Prospective, randomized clinical trial
      (Canadian Task Force classification I). SETTING: Academic research center.
      PATIENTS: One hundred women with abnormal uterine bleeding. INTERVENTIONS:
      Hysteroscopy with a 3.5-mm minihysteroscope or conventional 5-mm endoscope with
      no anesthesia. MEASUREMENTS AND MAIN RESULTS: Duration of examinations, pain, and
      occurrence of vasovagal reactions were recorded. Pain was assessed by visual
      analog scale ranging from zero to 20 before (pain expectancy) and at the end of
      the procedure. Occurrence of vasovagal reactions was assessed by monitoring blood
      pressure and pulse rate at 1-minute intervals during the procedure. A heart rate
      of less than 60/minute or a reduction greater than 20% compared with baseline was
      considered a vasovagal reaction; similarly, a reduction in blood pressure
      exceeding baseline value by 20% was considered a result of vagal stimulation.
      Mean duration was shorter for minihysteroscopy than for conventional
      hysteroscopy. The mean (SD) level of pain experienced during minihysteroscopy
      also was significantly lower (0.76 +/- 0.65 vs 1.46 +/- 0.86, 95% CI-1.0-0.4, p
      <0.0001). The number of instrumentally recorded (1 vs 11 cases) and clinical
      vasovagal reactions (0 vs 6 cases) was also significantly lower in the
      minihysteroscopy group than in the conventional hysteroscopy group (p <0.002 and
      <0.02, respectively). CONCLUSION: New-generation minihysteroscopes make
      hysteroscopy easier and less painful, and carry a lower risk of vasovagal
      reactions than hysteroscopy performed with conventional instruments. In our
      experience, minihysteroscopy with vaginoscopic approach and saline distention is
      well tolerated, effective, and a true outpatient procedure.

PMID- 14567823
TI  - Laparoscopic removal of large multiple myomas with cumulative weight of 2.3 kg.
AB  - Large multiple myomas with a cumulative weight of 2.3 kg were removed
      laparoscopically from a nulliparous 32-year-old woman. The patient's recovery was
      uneventful, and she has been eumenorrheic in the 2 years since surgery.

PMID- 14567824
TI  - Ovarian remnant with bilateral duplicate ureters.
AB  - A 27-year-old woman had a history of acute chronic pelvic pain. She had had a
      previous salpingo-oophorectomy for an endometrioma. A computerized tomographic
      scan showed a left adnexal mass. She was known to have bilateral duplicate
      ureters shown on intravenous pyelogram. She underwent laparoscopy and
      retroperitoneal dissection of endometriosis with excision of the mass from the
      pelvic sidewall. The final pathology was consistent with a hemorrhagic corpus
      luteal cyst.

PMID- 14567825
TI  - Laparoscopic excision of symmetric uterine remnants in a patient with mayer
      rokitansky-kuster-hauser syndrome.
AB  - Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is an infrequent developmental
      defect characterized by congenital absence of the vagina and uterus. Various
      anomalies of the mullerian system have been operated on by laparoscopy. We
      performed operative laparoscopy to remove symmetric uterine remnants and right
      ovarian endometrioma in a woman with MRKH syndrome who suffered from intractable
      lower abdominal pain. Both anomalous structures, which had true uterine vessels,
      were located on their respective pelvic sidewalls close to the ureters. We
      suggest that operative laparoscopy can be performed safely to treat these
      patients, but careful identification and dissection of the main blood supply, if
      necessary, are of substantial importance in order to avoid ureteral injury.

PMID- 14567826
TI  - Randomized comparison of the effect of manipulation on incisional parameters
      associated with a pyramidal laparoscopic trocar-cannula system and the EndoTIP
      cannula.
AB  - We conducted a randomized, controlled trial to evaluate the effect of
      laparoscopic access cannula manipulation on fascial and incisional
      characteristics in a white swine model, comparing a pyramidal trocar-cannula
      system (PTC) and a trocarless threaded cannula (TTC, EndoTIP). We made 6
      insertions in 10 animals. Cannulas randomized to the movement group were
      manipulated in standard fashion in skin and subcutaneous tissues. After
      dissection, muscle damage scores, wound areas, and maximum wound lengths were
      determined. Mean muscle damage scores without and with manipulation for the TTC
      were 0.7 and 1.00, respectively, and for the PTC 1.9 and 2.0. Differences between
      devices were significant (p = 0.0001) but there were no differences within
      devices (manipulation vs no manipulation). Mean wound length for the TTC without
      manipulation (0.699 cm) was less than that after manipulation (1.101 cm, p =
      0.0002). The mean nonmanipulated PTC wound length (0.968 cm) was more than that
      of corresponding TTC wounds (0.699 cm, p = 0.0082) but this difference was lost
      after manipulation (TTC 1.101, PTC 0.930). Mean wound area for the nonmanipulated
      TTC was less than that for corresponding PTC wounds (16.99 vs 30.85 mm(2), p =
      0.0066) but this difference was lost after manipulation (TTC 24.31 mm(2), PTC
      25.97 mm(2)). Thus cannula manipulation had no effect on wound area and an
      adverse effect on maximum wound length for the threaded cannula only. Despite
      movement, the muscle damage score remained significantly less for the threaded
      cannula.

PMID- 14567827
TI  - Safe laparoscopic entry guided by Veress needle CO2 insufflation pressure.
AB  - Laparoscopy was performed in 259 women. Under general anesthesia, after
      administering muscle relaxants, and with the patient in stirrups and horizontal
      position, a nondisposable Veress needle was inserted at the umbilicus or left
      upper quadrant site with carbon dioxide (CO2) flowing at 1 L/minute. We measured
      initial intraabdominal pressure in the first 52 women (group 1), pneumoperitoneum
      pressure (up to 15 mm Hg) at 1-L intervals in the next 102 women (group 2), and
      CO2 volume required for pressures of 10, 15, 20, and 25 mm Hg in the final 102
      women (group 3). In three patients the procedure was abandoned. The primary
      trocar and laparoscope were introduced at pressure of 25 mm Hg and the entry site
      and abdominal contents were inspected before desufflation to 15 mm Hg and
      Trendelenburg position. Medians and means of initial intraabdominal pressure were
      4 and 4.09 mm Hg (SD 1.34 mm Hg, range 2-8 mm Hg). This was always below
      interstitial pressures measured in the abdominal wall and during inadvertent
      insertion into omentum (5) and colon (2). Correlation between initial
      intraperitoneal pressure and patients' parity, weight, and body mass index was
      minimal. Mean CO2 volumes at 10, 15, 20, and 25 mm Hg were 3.7, 5.1, 5.9, and 6.5
      L, respectively. No major complications were encountered. An initial
      intraabdominal pressure of 8 mm Hg or below always indicates correct placement of
      the Veress needle regardless of the patient's body habitus. Pressures greater
      than 8 mm Hg indicate interstitial placement including colon. Adequate
      pneumoperitoneum is determined by CO2 insufflation to a pressure of 25 mm Hg and
      not by a preconceived volume of CO2.

PMID- 14567828
TI  - Cul-de-sac packing with a metreurynter in gasless laparoscopic cystectomy during
      pregnancy.
AB  - Gasless laparoscopic cystectomy was performed for a woman in the fifteenth week
      of pregnancy. An ovarian cyst that had been sinking behind the uterus appeared
      spontaneously after ballooning the metreurynter in the pouch of Douglas. This
      allowed extraperitoneal cystectomy, and the patient's subsequent antenatal course
      was uneventful. Cul-de-sac packing with a metreurynter permits gentle and
      atraumatic manipulation against the pregnant uterus.

PMID- 14567829
TI  - MycroMesh is not a suitable soft tissue prosthesis for repair of the defective
      vaginal wall.
AB  - Thirty-one women had recurrent vaginal wall prolapse repaired with insertion of a
      soft tissue prosthesis-MycroMesh in 22 (group B) and other materials in 9 (group
      A). Rejection rates were 18% and zero percent, respectively. Given these data,
      MycroMesh is not recommended to repair a defective vaginal wall.

PMID- 14567830
TI  - Maternally transferred neutralising dengue antibodies in Thai infants: a pilot
      study.
AB  - In a dengue-endemic area, sera from 42 mother-infant pairs and sera collected
      from the infants at follow-up at the ages of 3 months (n =27), 6 months (n =34),
      9 months (n =23) and 12 months (n =8) were tested for antibodies to four dengue
      serotypes using a plaque reduction neutralisation test (PRNT(50)), IgG ELISA and
      haemagglutination inhibition assay (HAI). The IgG ELISA and HAI tests were less
      sensitive than PRNT(50) in detecting low levels of antibodies. Levels of
      maternally transferred dengue neutralising antibodies in the cord sera were very
      high and identical to those in the mothers. Neutralising antibody prevalences in
      the newborns were 95% to dengue serotype 1 (DEN-1), 93% to DEN-2 and DEN-3 and
      91% to DEN-4. The antibodies decreased with increasing age. At least one dengue
      serotype neutralising antibody persisted in the infants at ages 3, 6 and 9 months
      in 92%, 69% and 13%, respectively. No maternally transferred antibody was
      observed in 12-month-old infants. In endemic areas therefore, where most infants
      have maternally transferred dengue antibodies, interference with dengue vaccine
      is likely to be less after 12 months of age than before then.

PMID- 14567831
TI  - Serum intercellular adhesion molecule-1 levels in acute rheumatic fever.
AB  - In order to determine the role of soluble intercellular adhesion molecule-1
      (sICAM-1) in the pathogenesis and course of acute rheumatic fever (ARF), serum
      levels of ICAM-1 were measured in 30 patients at onset of ARF, in remission and
      during inactive periods of the disease (group 1), in 20 patients who had had ARF
      at least a year beforehand and had no evidence of exacerbation of the disease
      (group 2) and in 20 healthy children. Serum levels of sICAM-1 were increased in
      group 1, peaking in the active phase of the disease and declining during
      remission to the inactive phase of the disease when they were still significantly
      higher than in the controls, despite their ESR and fibrinogen levels having
      fallen to normal limits. The levels in group 2 were similar to those in the
      healthy controls. We consider that ICAM-1 plays a role in the pathogenesis of ARF
      and that improvement of ARF might best be determined by serum sICAM-1 levels,
      even when clinical and other laboratory test results have returned to normal, but
      additional studies are needed to clarify this hypothesis.

PMID- 14567832
TI  - Aflatoxin M1 in breast-milk of UAE women.
AB  - A study was undertaken to determine whether breast-milk of mothers from the
      United Arab Emirates (UAE) contained aflatoxins. One hundred and forty lactating
      mothers, 55 who had delivered premature infants (<2500 g, </=37 wk gestational
      age) and 85 who had full-term infants, agreed to participate in the study. Breast
      milk was collected during regular feeding of infants in the special care baby
      unit and postnatal wards using an electric breast pump and ten ml of milk was
      siphoned off into a zinc-free plastic container for analysis. Aflatoxin M(1)
      concentration in the breast-milk samples was measured by HPLC. Samples were
      collected between January 1999 and December 2000. Approximately 66% of the
      mothers were expatriates and 34% were UAE nationals. Babies' weight, postnatal
      age, sex, birthweight and gestational age, and mothers' nationality, age and
      parity were recorded. Overall, 92% of the breast-milk samples contained aflatoxin
      M(1). Both univariate and multivariate logistic regression analysis failed to
      show significant correlation between aflatoxin M(1) and gestational age,
      postnatal age, gender, nationality and clinical condition. Levels of lactose,
      protein and lipids did not correlate significantly with levels of aflatoxin M(1).
      The public should be educated about storing food and the hazards of aflatoxin
      ingestion to reduce the unacceptably frequent presence of aflatoxin in breast
      milk.

PMID- 14567833
TI  - Dietary and socio-economic factors associated with beriberi in breastfed Lao
      infants.
AB  - A case-control study was conducted to investigate the dietary and socio-economic
      factors associated with beriberi in infants attending three public hospitals in
      Vientiane, Lao PDR. Forty-three breast-feeding infants with a median (range) age
      of 3 (1-9) months were admitted with beriberi. This was defined as the presence
      of signs of congestive heart failure or shock in the absence of fever or other
      signs of sepsis, hypovolaemia or cardiac abnormalities, with rapid clinical
      improvement following parenteral thiamine. Subjects were matched by age and diet
      to 43 breast-feeding healthy control infants. Compared with control mothers,
      mothers of infants with beriberi had significantly less diet diversity (p
      <0.001), soaked glutinous rice for significantly longer or were more likely to
      pour off excess water from non-glutinous rice (p =0.006), had fewer years of
      schooling (p <0.05), were more likely to report that income was inadequate for
      basic needs (p <0.001), to perform hard physical labour (p <0.01) and to be
      married to farmers (p <0.01). Clinically significant thiamine deficiency in
      breastfed infants in Lao relates to methods of preparing rice, the food selected
      by lactating mothers and the family's socio-economic status.

PMID- 14567834
TI  - Kawasaki disease resistant to immunoglobulin G therapy.
AB  - We describe a 3-year-old boy with Kawasaki disease who, despite therapy with two
      doses of intravenous immunoglobulin G and high-dose aspirin, developed
      myocarditis in the 1st week of illness and coronary artery aneurysms in the 2nd
      week. He required a short course of systemic corticosteroids for remission of the
      illness. The myocarditis subsided and coronary aneurysms remained static and
      uncomplicated during 6 weeks of follow-up. The diagnosis and recent trends in
      management of this not uncommon vasculitic disorder are outlined.

PMID- 14567835
TI  - Delayed visual maturation in Karen refugee infants.
AB  - Thirty-eight babies born to Karen mothers living in camps for displaced persons
      in north-western Thailand have delayed visual maturation (DVM type 1) that
      recovers within 6 months. Vitamin A concentrations were deficient in 16% of
      breast-milk samples from lactating mothers and vitamin B(1) concentrations were
      deficient in 60% of plasma samples. Infantile beriberi was common in this
      population. The levels of fatty acids in plasma and milk in Karen women were
      excellent at birth and in the postpartum period. The degree of deficiencies in
      these vitamins and the concentration of essential fatty acids in cord blood and
      maternal breast-milk did not correlate significantly with visual impairment in
      the infants. DVM might be caused by nutritional deficiency or toxic effects
      during critical periods of gestation that lead to delayed cortical myelination or
      structural defects which impinge on parietal cortex function.

PMID- 14567836
TI  - Neonatal transfusion malaria requiring exchange transfusion.
AB  - Transfusion-acquired malaria in a neonate is uncommon and factors such as drug
      resistance and concomitant G6PD deficiency can cause treatment difficulties. We
      report a 26-day-old premature infant with chloroquine-resistant malaria who
      underwent exchange transfusion. The aim was to correct anaemia, decrease
      parasitaemia and remove G6PD-deficient cells to allow successful use of quinine.

PMID- 14567837
TI  - A cross-sectional survey of the growth and nutrition of the Bedouin of the South
      Sinai Peninsula.
AB  - A total of 271 Bedouin, 140 of them younger than 16 years and 110 of them female,
      were examined as part of a health survey. The Bedouin of the southern Sinai
      showed evidence of stunted growth. Sixty-six subjects (24 female) were clinically
      anaemic. This might have been nutritional or secondary to giardiasis. Simple
      nutritional strategies to increase the protein and iron content of the diet might
      help to prevent these problems. Twenty Bedouin had sensorineural hearing loss
      that was thought to be autosomal recessive in one family grouping. In addition,
      ten adults had had an uvulectomy, a traditional means of thirst quenching.

PMID- 14567838
TI  - Spinal Burkitt's lymphoma manifesting as nocturnal abdominal pain and
      constipation: a case report.
AB  - A 3-year-old boy presented at the Taiwan Adventist Hospital in Taipei with
      nocturnal epigastric pain and constipation. Abdominal X-ray showed colonic faecal
      impaction. Abdominal sonography showed gastric stasis with thickened pyloric wall
      and dilated rectosigmoid colons. The mouth-to-anus transit time (MATT) was
      prolonged. Endoscopy showed pale gastric mucosa, atony of pylorus and widening of
      the duodenal bulb. Three weeks after the onset of abdominal pain, he developed
      urinary incontinence and rapidly deteriorating paraplegia of lower limbs.
      Magnetic resonance imaging (MRI) showed an extradural intraspinal mass of T5-T8
      and a soft tissue mass in the right superior mediastinum. After a laminectomy and
      tumour excision, the patient's symptoms improved quickly. The pathology revealed
      Burkitt's lymphoma. This is the first report of nocturnal abdominal pain and
      constipation as the initial manifestation of spinal Burkitt's lymphoma.

PMID- 14567839
TI  - Urinary tract infection in febrile children with sickle cell anaemia.

PMID- 14567840
TI  - On being loud and proud: non-conformity and counter-conformity to group norms.
AB  - Most experiments on conformity have been conducted in relation to judgments of
      physical reality; surprisingly few papers have experimentally examined the
      influence of group norms on social issues with a moral component. In response to
      this, participants were told that they were either in a minority or in a majority
      relative to their university group in terms of their attitudes toward recognition
      of gay couples in law (Expt 1: N = 205) and a government apology to Aborigines
      (Expt 2: N = 110). In both experiments, it was found that participants who had a
      weak moral basis for their attitude conformed to the group norm on private
      behaviours. In contrast, those who had a strong moral basis for their attitude
      showed non-conformity on private behaviours and counter-conformity on public
      behaviours. Incidences of non-conformity and counter-conformity are discussed
      with reference to theory and research on normative influence.

PMID- 14567841
TI  - The 'good father': reading men's accounts of paternal involvement during the
      transition to first-time fatherhood.
AB  - The study investigates men's responses to contemporary sociocultural
      transformations in masculinity and fatherhood, and revised expectations of them
      as fathers. Four cultural and academic perspectives on 'new fatherhood' are
      described: a progressive psychosocial transformation agenda, attempts to
      reinstate traditional family values, a mix of optimism and resistance to change
      in men and fathers' relationship to the gender order, and criticism of new
      fatherhood discourse for reproducing hegemonic masculinity. A qualitative
      analysis is conducted of interviews conducted with a heterogeneous sample of 30
      men aged 18-35 years in Norfolk. Interviewees overwhelmingly welcomed the
      opportunities offered to them by the new fatherhood model and supported a
      perceived cultural shift towards men and fathers being involved in, rather than
      detached from, family life. But three areas of tension and difficulty in living
      the ideal were also reported: providing cash and care; valuing selflessness and
      autonomy; and negotiating fairness, equity and decision making (for fathers who
      rather than helping out wanted full involvement in child care). We conclude that
      neither the 'hegemonic masculinity' nor the 'men as part of the family'
      perspectives exhaust the options for reading the gratifications and tensions
      advanced in men's accounts of living contemporary fatherhood. Arguments for
      greater balance in appreciating the problems and advantages of new fatherhood, or
      that men need to undergo greater change, also fail to offer points of closure.

PMID- 14567842
TI  - Tests of both corollaries of social identity theory's self-esteem hypothesis in
      real group settings.
AB  - The present study tests both corollaries of the self-esteem hypothesis from
      social identity theory derived by Abrams and Hogg (1988). Greek students
      completed a pre-test collective self-esteem (CSE) measure and then rated Greek
      students and either American or Turkish students. They then completed a post-test
      collective self-esteem measure. Inconsistent with Corollary 2, higher prior CSE
      was associated both with higher in-group ratings and higher out-group ratings,
      but not with bias. Consistent with Corollary 1, change in CSE was positively
      associated with bias, positively associated with in-group ratings and negatively
      associated with out-group ratings. There were no differences due to type of out
      group. The findings are consistent with the idea that, for specific comparisons
      between real groups, individual differences in self-esteem may affect the zone
      within which bias occurs rather than the amount of bias. However, achieving
      increases in self-esteem depends on establishing positive distinctiveness for the
      in-group in the context of a specific intergroup comparison.

PMID- 14567843
TI  - Discourses about ethnic group (de-)essentialism: oppressive and progressive
      aspects.
AB  - Social psychologists studying intergroup perceptions have shown an increasing
      interest in essentialist thinking. Essentialist beliefs about social groups are
      examined as cognitive processes and these beliefs would serve to rationalize and
      justify the existing social system. Discourse analyses on racism have emphasized
      that problems of racism are to a large extent problems of essentialism. Anti
      essentialism has emerged as an emancipatory discourse in the challenge of
      hegemonic representations and oppressive relations. The present study examines
      how, in group discussions, ethnic Dutch and ethnic minority people define and use
      essentialist notions about social groups. Both Dutch and ethnic minority
      participants engaged in an essentialist discourse in which an intrinsic link
      between culture and ethnicity was made. However, there were also examples where
      this discourse was criticized and rejected. This variable use of (de
      )essentialism is examined in terms of the conversation's context and issues at
      hand, such as questions of assimilation, group provisions, cultural rights, and
      agency. The main conclusion of this paper is that essentialism is not by
      definition oppressive and that de-essentialism is not by definition progressive.
      The discursive power of (de-)essentialist group beliefs depends on the way they
      are used and the context in which they appear.

PMID- 14567844
TI  - Predicting behaviour from perceived behavioural control: tests of the accuracy
      assumption of the theory of planned behaviour.
AB  - The theory of planned behaviour assumes that the accuracy of perceived
      behavioural control (PBC) determines the strength of the PBC-behaviour
      relationship. However, this assumption has never been formally tested. The
      present research developed and validated a proxy measure of actual control (PMAC)
      in order to test the assumption. In two studies, participants completed measures
      of intention and PBC, and subsequently completed measures of behaviour and the
      PMAC. Validity of the PMAC was established by findings showing; (a). that the
      PMAC moderated the intention-behaviour relation, and (b). that PMAC scores did
      not reflect attributions for participants' failure to enact their stated
      intentions. Accuracy was operationalized as the difference between PBC and PMAC
      scores. Consistent with theoretical expectations, several analyses indicated that
      greater accuracy of PBC was associated with improved prediction of behaviour by
      PBC.

PMID- 14567845
TI  - Shared impression formation in the cognitively interdependent dyad.
AB  - We examined the role of cognitive interdependence in determining how close
      friends form shared impressions of another person. Cognitive interdependence
      should provide a processing advantage, such that close friends are more efficient
      in forming shared impressions and are more successful at doing so. Under normal
      circumstances, the conversations of close friends should be marked by little
      necessity to make explicit requests for information, mutual recognition of who
      currently is controlling the flow of conversation, and willingness to express
      differences in opinion. Given these advantages, close friends also should be able
      to form complex shared impressions that go beyond mere one-sided stereotypic
      judgments and that instead resolve apparent discrepancies in the target's
      personality. However, if the cognitive interdependence system is disrupted by
      mutual distraction, these advantages should attenuate or even reverse. Dyads of
      varying degrees of closeness were mutually distracted or not while discussing
      their impressions of another female college student. Results supported
      predictions and are discussed with reference to how cognitive interdependence may
      help close dyads function within their mutual social networks.

PMID- 14567846
TI  - Mentality or morality? Membership categorization, multiple meanings and mass
      murder.
AB  - A central topic for social psychology is how we identify, categorize or represent
      ourselves to ourselves and to each other. Previous work on this topic stemming
      from attribution theory, social identity theory, self-categorization theory and
      social representations theory has tended to accept the dominant cognitivist tenet
      of an interior self which is (with varying degrees of success) re-presented in
      ordinary discourse. Against this tradition, and drawing on membership
      categorization analysis, we argue here for an attention to ordinary members'
      methods of categorizing the self. Such devices are constitutive of a culture.
      Accounts of the self (whether lay or professional) cannot avoid reliance on such
      devices. Our particular case involves a corpus of materials from the press
      surrounding the Port Arthur massacre: the shooting of 35 people by a lone gunman,
      Martin Bryant, in Tasmania in 1996. In this case, where public accountings for
      what 'makes up' a particular person are tied to an otherwise inexplicable but
      ultra-newsworthy event, we find that lay and professional methods of accounting
      are remarkably congruent. One of the reasons for this congruence, we suggest, is
      that the categorization of persons is a fundamentally moral matter. Devices for
      producing everyday moral accounts, in actual practical circumstances, precede and
      ground, for example, 'technical', 'clinical' or 'scientific' judgments. We
      conclude that describing such routine (but ultimately grounding) cultural devices
      can be a central goal of social psychology, as opposed to explaining 'the self'
      by tacitly relying upon those same devices in an unacknowledged and
      unproblematized fashion.

PMID- 14567847
TI  - Self-views in close relationships: the influence of attachment styles.
AB  - Two studies were conducted to test the hypothesis that self models (positive vs.
      negative) determine whether temporarily accessible information changes one's self
      evaluations. Regularly dating participants were led to review selectively their
      relationship-related behaviours which had either favourable or unfavourable
      implications for their close relationships. Based on the four-group model of
      attachment (secure, preoccupied, fearful, and dismissing; Bartholomew, 1990),
      attachment orientations were either assessed (Study 1) or activated by a guided
      imagination task (Study 2). The results show that participants holding a negative
      model of the self were more susceptible to variations in accessible information
      than those holding a positive model of the self. Their self-evaluations shifted
      in the positive direction when positive information was salient and in the
      negative direction when negative information was salient. Secure and dismissing
      (positive self model) participants were largely unaffected by the salience
      manipulation. The results are discussed in light of theories that propose a
      dynamic self-concept.

PMID- 14567848
TI  - Combining classificatory and discursive methods: consistency and variability in
      responses to the threat of crime.
AB  - This paper explores the implications for social psychology of an integration of
      classificatory and discursive methodologies through quantitative and qualitative
      analysis of responses to questions about the threat of violent crime. A total of
      133 adults completed a set of standard questions followed by open-ended prompts
      enabling elaboration on their responses. Cluster analysis of a set of fear of
      crime measures distinguished four groups of respondents. Interview transcripts
      were analysed to identify discourses around crime deployed within each cluster in
      order to justify risk/anxiety judgments. Four participant positions emerge: the
      well-protected position, the vigilant position, the tactical risk manager and the
      besieged position. Further analysis of inconsistency and variability within
      interviews reveals the interactional discursive processes involved in the
      construction of criminal threat. Despite the diversity of participant positions
      available in constructing criminal threat and managing anxiety, discourses
      revolve centrally around issues of agency and uncontrollability.

PMID- 14567870
TI  - Avoiding the 'dataset mentality'.

PMID- 14567871
TI  - Do information systems meet the needs of primary care trusts?
AB  - To function effectively, primary care trusts (PCTs) need information from a range
      of sources. The general practice clinical record is a key source of information
      for PCTs but has often proved to be of variable quality. PCTs have developed
      rapidly and now have responsibility for 75% of the healthcare budget. They have a
      range of information needs that must be met if they are to ensure that healthcare
      provision meets the needs of patients. Since the abolition of health authorities
      PCTs have full responsibility for developing practice systems as well as having a
      key role to play in developing information management and technology (IM&T)
      within local health economies. The paper describes the problems PCTs face in
      accessing information to support their core functions and the progress they have
      made in retrieving data to support service development. It also describes the
      progress and developments in information and information systems within general
      practice using data from the National Tracker Survey of Primary Care Groups and
      Trusts (PCG/Ts). The survey began in 1999 when PCGs were established and has
      tracked the progress of PCG/Ts over three years. This paper presents the findings
      from the third survey relating to the development of information to support the
      needs of PCG/Ts. The findings show that information available to PCG/Ts does not
      meet their needs in a range of key areas. Many PCG/Ts are collecting data to
      support the Coronary Heart Disease National Service Framework (CHD NSF) and
      monitoring some areas of service provision in general practice. The use of
      information management tools has risen significantly since the second survey and
      involvement in the Primary Care Information Services (PRIMIS) initiative has more
      than doubled. The paper concludes that although PCG/Ts and general practices have
      made substantial progress, there is a long way to go before information providers
      generate high-quality information to support the needs of PCTs.

PMID- 14567872
TI  - Consultation computer use to improve management of chronic disease in general
      practice: a before and after study.
AB  - BACKGROUND: Computers have become widespread in primary care but their potential
      to improve clinical effectiveness has not been completely fulfilled. One
      explanation for this is the difficulty in evaluating their impact on the process
      of care. AIM: To determine the effects of computers in consulting rooms on the
      management of chronic disease. METHODS: Before and after study with concurrent
      control group, matching six practices moving from paper-based recording to a
      consultation-based computer environment, with six practices using paper-based
      systems. Data were collected retrospectively via case note review for the year
      preceding the arrival of the computers and for the subsequent year. All patients
      with diagnosed diabetes mellitus (n = 1070) or rheumatoid disease (n = 202) were
      included. The main outcome measure was recording of disease management items.
      RESULTS: The computer group improved recording for seven of the eight diabetic
      and four of the seven rheumatoid items studied. Increases were significant for
      height (5% increase; 95% confidence interval (CI): 1.2% to 8.8%), weight (6.6%;
      95% CI: 2.2% to 11.0%), foot pulses (8.7%; 95% CI: 4.1% to 13.4%), foot sensation
      (8.6%; 95% CI: 5.2% to 11.9%), blood pressure (12.6%; 95% CI: 2.0% to 23.2%) and
      urinalysis (20.2%; 95% CI: 11.0% to 29.4%). The control group improved for two
      diabetic and five rheumatoid items, the only significant increase being for
      urinalysis (1.1%; 95% CI: 0.2% to 22.0%). Computer use was associated with
      increased recording of each diabetes item except fundoscopy, and with increased
      blood pressure recording for rheumatoid disease. The larger the practice, the
      larger the effects observed. CONCLUSIONS: Use of computers can improve management
      of chronic disease in primary care. Impact is most clearly seen in those items
      easily recorded on computer during consultations. Effects are most evident in
      practices with larger patient numbers.

PMID- 14567873
TI  - The efficacy of an automated feedback system for general practitioners.
AB  - OBJECTIVE: An automated feedback system that produces comments about the non
      adherence of general practitioners (GPs) to accepted practice guidelines for
      ordering diagnostic tests was developed. Before implementing the automated
      feedback system in daily practice, we assessed the potential effect of the system
      on the test ordering behaviour of GPs. DESIGN: We used a randomised controlled
      trial with balanced block design. SETTING: Five times six participant groups of
      GPs in a computer laboratory setting. INTERVENTION: The GPs reviewed a random
      sample of 30 request forms they filled in earlier that year. If deemed necessary,
      they could make changes in the tests requested. Next, the system displayed
      critical comments about their non-adherence to the guidelines as apparent from
      the (updated) request forms. SUBJECTS: Twenty-four randomly selected GPs
      participated. MAIN OUTCOME MEASURES: The number of requested diagnostic tests
      (17% with 95% confidence interval [CI]: 12-22%) and the fraction of tests ordered
      that were not in accordance with the practice guidelines (39% with 95% CI: 28
      51%) decreased due to the comments of the automated feedback system. The GPs
      accepted 362 (50%) of the 729 reminders. IMPLICATIONS: Although our experiment
      cannot predict the size of the actual effect of the automated feedback system in
      daily practice, the observed effect may be seen as the maximum achievable.

PMID- 14567874
TI  - Comparing the use of health information/advice in Birmingham and Hull: a case
      study of digital health information delivered via the television.
AB  - Postal questionnaire surveys were carried out with users of two digital
      interactive television (DiTV) providers of health content to investigate the use
      made of each service and the users' reactions to service content and its
      usefulness to them. The research indicated that health information on DiTV was
      used and, on the whole, rated favourably. There was some evidence also that such
      information might be used by some people as a substitute for going to the doctor,
      though information from their general practitioner (GP) or practice nurse still
      carries more weight for most people than any other health information source.
      This study forms part of an ongoing research project which has, as part of its
      aim, the task of identifying particular users with the information sources that
      may be most appropriate for them.

PMID- 14567875
TI  - Moving toward a United States strategic plan in primary care informatics: a White
      Paper of the Primary Care Informatics Working Group, American Medical Informatics
      Association.
AB  - The Primary Care Informatics Working Group (PCIWG) of the American Medical
      Informatics Association (AMIA) has identified the absence of a national strategy
      for primary care informatics. Under PCIWG leadership, major national and
      international societies have come together to create the National Alliance for
      Primary Care Informatics (NAPCI), to promote a connection between the informatics
      community and the organisations that support primary care. The PCIWG clinical
      practice subcommittee has recognised the necessity of a global needs assessment,
      and proposed work in point-of-care technology, clinical vocabularies, and
      ambulatory electronic medical record development. Educational needs include a
      consensus statement on informatics competencies, recommendations for curriculum
      and teaching methods, and methodologies to evaluate their effectiveness. The
      research subcommittee seeks to define a primary care informatics research agenda,
      and to support and disseminate informatics research throughout the primary care
      community. The AMIA board of directors has enthusiastically endorsed the
      conceptual basis for this White Paper.

PMID- 14567876
TI  - Three steps to data quality.
AB  - BACKGROUND: The quality of data in general practice clinical information systems
      varies enormously. This variability jeopardizes the proposed national strategy
      for an integrated care records service and the capacity of primary care
      organisations to respond coherently to the demands of clinical governance and the
      proposed quality-based general practice contract. This is apparent in the
      difficulty in automating the audit process and in comparing aggregated data from
      different practices. In an attempt to provide data of adequate quality to support
      such operational needs, increasing emphasis is being placed on the
      standardisation of data recording. OBJECTIVE: To develop a conceptual framework
      to facilitate the recording of standardised data within primary care. METHOD: A
      multiprofessional group of primary care members from the South Thames Research
      Network examined leading guidelines for best practice. Using the nominal group
      technique the group prioritized the information needs of primary care
      organisations for managing coronary heart disease according to current evidence.
      RESULTS: Information needs identified were prioritized and stratified into a
      functional framework. CONCLUSION: It has been possible within the context of a
      primary care research network to produce a framework for standardising data
      collection. Motivation of front-line clinicians was achieved through the
      incorporation of their views into the synthesis of the dataset.

PMID- 14567877
TI  - Are major defects in children conceived in vitro due to innate problems in
      patients or to induced genetic damage?
AB  - Birth anomalies recently detected in epidemiological studies indicate greater
      risks following assisted human reproduction than with natural conception. Some of
      these conclusions and assumptions are questioned in this paper, and the effects
      of specific causative factors unique to some infertile couples are analysed.
      Other recent studies have identified imprinting defects as causes of birth
      disorders following IVF or intracytoplasmic sperm injection. While few in
      numbers, they apparently involve unusual factors in conception such as aberrant
      responses among preimplantation embryos to culture medium or serum. Various
      genetic and developmental factors in infertile couples influencing the origin of
      such birth outcomes are assessed, and the significance of imprinting and its
      embryological roles are discussed.

PMID- 14567878
TI  - Horses added to the list of cloned species.

PMID- 14567879
TI  - Gamete donation - where is the evidence that there are benefits in removing the
      anonymity of donors? A patient's viewpoint.
AB  - The Department of Health has recently initiated a consultation exercise seeking
      input on the subject of removing gamete donor anonymity. This paper examines the
      case for disclosure alongside that of providing additional non-identifying
      information. The author questions the availability of scientifically based
      research to demonstrate that children's best interests can only be served by the
      provision of identifying information. The author also questions whether all the
      possible implications of legislative change have been identified and debated. The
      paper states that the harmful effects of disclosure on the lives of other
      interested parties, an inevitable downward trend on donor numbers, and a negative
      emotional impact in the event of a mismatch in expectations between donors and
      donor offspring guard against the identification of gamete donors. It is proposed
      that egg share schemes without anonymity, possibly the only reliable source of
      donor eggs, would become impractical in the UK. It concludes that given the far
      reaching and irreversible impact of disclosure, the removal of anonymity should
      be considered only when research provides unequivocal proof that improved levels
      of non-identifying information are insufficient for the well-being of donor
      offspring.

PMID- 14567880
TI  - A dedicated surrogate mother.

PMID- 14567881
TI  - Current status of preimplantation diagnosis for single gene disorders.
AB  - Preimplantation genetic diagnosis (PGD) has become an established procedure for
      avoiding the birth of affected children with single gene disorders. PGD is
      performed through polar body or blastomere biopsy, which has no deleterious
      effect on pre- and post-implantation development. This review describes the most
      recent developments and current changes in the spectrum of conditions for which
      PGD has been applied. The most recent applications of PGD include congenital
      malformations, blood group incompatibility and an increasing number of late onset
      disorders with genetic predisposition, all of which have not previously been
      diagnosed using PGD. Despite ethical concerns, PGD has also been used for
      preselection of unaffected and HLA matched embryos, and recently for
      preimplantation HLA matching without testing for the causative gene. This extends
      the practical value of PGD, with its utility being no longer limited to
      prevention of single gene disorders, by expanding it to treatment of siblings
      requiring stem cell transplantation.

PMID- 14567882
TI  - Decidualization of the human endometrial stromal cell: an enigmatic
      transformation.
AB  - Changes in human endometrium are essential to allow the establishment of
      pregnancy. These changes are induced in vivo by progesterone, and include
      appearance within the tissue of a specific uterine natural killer cell,
      characterized by an abundant expression of CD56. Changes also occur in the
      stromal cells, which undergo a characteristic decidualization reaction.
      Decidualized stromal cells are derived from the fibroblast-like cells within the
      endometrium, which maintain their progesterone receptors in the presence of
      progesterone. Prolonged exposure to progesterone induces a rounded cell
      characterized by release of prolactin and insulin-like growth factor binding
      protein-1 (IGFBP-1), and expression of tissue factor. Additional changes include
      the secretion of interleukin (IL)-15, vascular endothelial growth factor, and
      surface expression of zinc dependent metalloproteinases such as CD10 and CD13. In
      vitro, elevated intracellular cAMP as well as progesterone is necessary for
      decidualization. In vivo, these conditions may be provided by progesterone from
      the corpus luteum, by prostaglandin E, a stimulator of adenyl cyclase, and
      relaxin, which has recently been shown to be a phosphodiesterase inhibitor. Given
      the co-distribution of uterine natural killer cells and decidualized stromal
      cells, a mutual interaction might provide the correct regulatory environment for
      successful implantation, and penetration of the maternal blood vessels by
      trophoblastic cells.

PMID- 14567883
TI  - Heritability and candidate genes for endometriosis.
AB  - Endometriosis is inherited in polygenic/multifactorial fashion, with recurrence
      risks of 5-7% for first-degree relatives. The current task is to determine the
      number and location of causative genes. This review initially supports the basis
      for polygenic/multifactorial inheritance and then outlines genome-wide strategies
      for identifying causative genes. Potential candidate genes are surveyed, and
      discrepant results emphasized. Finally, a hypothesis for endometriosis, having a
      multi-step pathogenesis analogous to the pathogenesis of neoplasia, is
      considered.

PMID- 14567884
TI  - Bone marrow stromal cells are highly pluripotent.

PMID- 14567885
TI  - Prediction of chances for success or complications in gonadotrophin ovulation
      induction in normogonadotrophic anovulatory infertility.
AB  - This follow-up study evaluated whether initial screening characteristics predict
      treatment outcome of gonadotrophin induction of ovulation. One hundred and fifty
      four women with normogonadotrophic anovulatory infertility for whom clomiphene
      citrate induction of ovulation was unsuccessful were included in the present
      study. Daily FSH injections were initiated on day 3-5 after spontaneous or
      progestagen-induced withdrawal bleeding. In most patients, a dose finding low
      dose step-up regimen was applied during the first treatment cycle in order to
      identify the individual FSH response dose. In all subsequent cycles, a step-down
      protocol was applied. Initial serum concentrations of LH, testosterone and
      androstenedione were significant predictors for the probability of multi
      follicular development. FSH treatment resulted in a total of 67 (44%) ongoing
      pregnancies. Comparing those women who did, versus those who did not, achieve an
      ongoing pregnancy in a multivariate Cox regression analysis, initial serum
      insulin-like growth factor-I (IGF-I), testosterone and women's age entered into
      the final model (AUC = 0.67). The individual treatment outcome following
      gonadotrophin induction of ovulation may be predicted by initial screening
      characteristics.

PMID- 14567886
TI  - Beneficial effects of GnRH agonist administration prior to ovarian stimulation
      for patients with a short follicular phase.
AB  - A short follicular phase is an early clinical feature of declining reproductive
      competence. The shortening of the follicular phase length is related to both
      advanced recruitment and selection of the dominant follicle secondary to an
      earlier and higher FSH rise during the luteal-follicular transition, while the
      late follicular growth is normal. As a short follicular phase may be detrimental
      for reproduction, it was postulated that increasing the duration of follicular
      phase could improve conception rate. For that purpose, gonadotrophin-releasing
      hormone agonist minidoses were administered in the mid-luteal phase to prevent
      the intercycle FSH rise before tailoring follicular growth by controlled
      exogenous FSH administration. This regimen, applied to 69 infertile ovulatory
      women with a short follicular phase (9.6 +/- 1.2 days) actually lengthened the
      follicular phase by about 3 days. It proved to be effective in 179 cycles to
      induce paucifollicular development (1.8 +/- 0.9 follicles) with a low
      cancellation rate (4%) and a moderate requirement for gonadotrophins [13.3 +/-
      6.3 ampoules (75 IU)]. In those women with a high frequency (80%) of elevated
      basal FSH or oestradiol concentrations, the pregnancy rate reached 15.1%/cycle
      but the miscarriage rate remained high (44%). Thus, increasing the follicular
      phase length in patients with a short follicular phase may partially restore
      fecundity.

PMID- 14567887
TI  - Depot GnRH agonist versus the single dose GnRH antagonist regimen (cetrorelix, 3
      mg) in patients undergoing assisted reproduction treatment.
AB  - The objective of this study was to compare, in a centre with previous experience
      of gonadotrophin-releasing hormone (GnRH) antagonist use, single administration
      of a GnRH antagonist [cetrorelix (Cetrotide) 3 mg] with a single administration
      of a GnRH agonist [Decapeptyl Retard 3.75 mg] in patients undergoing assisted
      reproduction treatment (n = 307 and 364 respectively). GnRH agonist was
      administered on the first day of menses, while cetrorelix was administered when
      the largest follicle reached 14 mm. Ovarian stimulation was performed with
      recombinant human FSH (r-hFSH; 150-225 IU/day). Human chorionic gonadotrophin
      (HCG, 10,000 IU) was administered when at least two follicles reached a mean
      diameter > or =18 mm. Over 90% of patients in both groups reached the criteria
      for HCG administration and underwent oocyte retrieval and embryo transfer.
      Duration of FSH therapy (9.95 versus 11.25 days) and cumulative dose of r-hFSH
      (1604 versus 1980 IU) were significantly reduced (P < 0.01) in the cetrorelix 3
      mg group. The number of oocytes retrieved was lower (8.5 versus 11.2; P < 0.01)
      with cetrorelix, but the number of embryos replaced was similar (2.2 versus 2.3;
      NS). The pregnancy rates per oocyte retrieval were the same, 24.5%, in the
      antagonist and agonist groups. This study indicates that although fewer oocytes
      are recovered, similar pregnancy rates can be achieved with a GnRH antagonist
      compared with a GnRH agonist. Additionally, a single dose of 3 mg cetrorelix was
      administered in 84% of patients, thus being simpler and more convenient for
      patients. Cetrorelix 3 mg may thus be proposed as a first choice for preventing
      both a premature LH surge and detrimental rises in LH during ovarian stimulation
      prior to assisted reproduction treatment.

PMID- 14567888
TI  - Relationship between LH and oestradiol in IVF cycles before GnRH antagonist
      initiation.
AB  - The objective of this prospective study was to assess the relationship of LH and
      oestradiol on day 7 of the cycle in patients stimulated with recombinant FSH (rec
      FSH) for IVF before initiation of gonadotrophin-releasing hormone (GnRH)
      antagonist. One hundred and forty-six women treated for IVF using GnRH
      antagonists for premature LH rise suppression were stimulated with 150 IU of rec
      FSH from day 2 to day 6 of the cycle. On cycle day 7, LH concentrations (median
      1.8, range 0.1-7.51) were positively associated with oestradiol concentrations on
      the same day by multiple regression analysis controlling for patient's age,
      concentrations of FSH and LH on cycle day 2, FSH concentrations on cycle day 7
      and follicular index on cycle day 7. In conclusion, the higher the endogenous
      unsuppressed LH concentrations on day 7 of the cycle after 5 days of stimulation
      with rec-FSH for IVF, the higher the serum oestradiol concentrations on the same
      day.

PMID- 14567889
TI  - Scandinavia is the tops in European IVF.

PMID- 14567890
TI  - Premature LH and progesterone rise in intrauterine insemination cycles: analysis
      of related factors.
AB  - Premature LH and progesterone surges are associated with different factors and
      hormonal modulators. The aim of the present study was (i) to investigate the
      clinical and laboratory factors and (ii) to highlight the importance of different
      stimulation protocols in associated premature LH and progesterone surges in
      intrauterine insemination (IUI) cycles. The study involved a retrospective
      investigation of 75 patients undergoing IUI for infertility treatment (135 IUI
      cycles) between 1996 and 2000, with initial serum LH concentrations >10 mIU/ml
      during ovarian stimulation. Ultrasound characteristics, follicular sizes, serum
      oestradiol, progesterone and LH concentrations and ovarian stimulation protocols
      were measured. There was a wide range of oestradiol serum concentrations (93-2245
      pg/ml) and follicular size (12-25 mm). In 49.6% of cycles, the dominant follicle
      was <16.5 mm. Patients with >2 follicles measuring <15 mm had higher oestradiol
      serum concentrations (P = 0.008). Multiple regression analyses revealed no
      association between these variables and premature LH/progesterone surge. In
      conclusion, LH/progesterone surges cannot be predicted utilizing clinical
      parameters normally employed, e.g. ultrasound serum oestradiol assay or ovarian
      stimulation protocol. Patients with follicles >14 mm or more and with high
      numbers of small follicles and high oestradiol are at risk of a spontaneous LH
      surge. These variables can be used to time the administration of GnRH antagonist
      administration until better predictive factors are demonstrated.

PMID- 14567892
TI  - Evaluation of functional ovarian reserve in 60 patients.
AB  - Diminished ovarian reserve is a condition occurring in women at any adult age,
      although it is more frequent in women in their 30s and in couples with
      unexplained subfertility. Different tests are employed to diagnose the problem.
      The most common are basal tests for FSH, LH, oestradiol and inhibin B, or dynamic
      endocrine tests such as the clomiphene citrate challenge test and gonadotrophin
      analogue stimulating test. In recent years, great attention has been devoted to
      direct tests such as the antral follicle count and ovarian biopsy results. The
      basal FSH concentration is the most common test utilized for ovarian screening.
      An abnormal value is correlated with a decrease in pregnancy rate and an increase
      in cycle cancellation rate. Among other basal endocrine tests, inhibin
      concentrations appear promising, although more data are necessary before this can
      be included in clinical practice. The clomiphene citrate challenge test can
      unmask patients who might have not been detected by basal FSH screening alone,
      and appears to be more sensitive than day 3 FSH alone. A prospective study was
      performed on the simultaneous application of various markers of ovarian reserve
      (FSH, LH, oestradiol, inhibin B, antral follicle count) in the natural cycle
      preceding assisted reproductive therapy, in 60 women. The present study suggests
      that counting ovarian follicles by ultrasound appears, at the moment, the most
      reliable test of ovarian reserve, although it is influenced by subjective factors
      and more studies are needed in order to confirm its predictive value.

PMID- 14567893
TI  - Oocyte-sperm interaction in the course of IVF: a scanning electron microscopy
      analysis.
AB  - Interaction between the spermatozoon and the zona pellucida during the first
      steps of fertilization was analysed on approximately 500 polyploid and
      unfertilized IVF oocytes by scanning electron microscopy (SEM). Oocytes
      demonstrate high inter- and intra-individual variations in size and morphology
      which do not correlate either with the maturity of the oocytes or with the age of
      the women. During gamete interaction, corona radiata cells are widely dispersed
      around the zona but are still in contact with it through cytoplasmic filaments.
      Channels between granulosa cells guide spermatozoa towards the zona. In the
      course of fertilization, different types of attachment of the spermatozoon to the
      oocyte occur. Most commonly, a flat, tangential attachment of the sperm head to
      the surface of the zona appears, which is then followed by intrusion into the
      zona in precisely this horizontal position. However, vertical binding with
      penetration by the tip of the head first also occurs. In oocytes where large,
      cluster-like numbers of bound spermatozoa are visible, vertical binding and
      penetration is the most usual position. In the process of gamete interaction,
      both spermatozoa and zona pellucida are actively involved. Spermatozoa, including
      their tails, which are attached to the zona, are overgrown by filaments of zona
      material. These filaments of the zona are made of granules, which are the basic
      components of zona material. After the removal of the zona pellucida by laser,
      the oolemma becomes visible. It is covered by microvilli of highly variable
      numbers. Between these microvilli, cortical granules are evident, and appear even
      before sperm penetration.

PMID- 14567894
TI  - Modified vitrification of human pronuclear oocytes: efficacy and effect on
      ultrastructure.
AB  - The efficacy of cryopreservation by direct plunging into liquid nitrogen
      (vitrification) of human pronuclear oocytes using open pulled straws with a super
      finely pulled tip, as well as the ultrastructural changes caused by cooling and
      vitrification, were evaluated. Clinical and electron microscopic studies of
      cooled and vitrified oocytes were performed. Oocytes were cooled to 4 degrees C
      in the presence and absence of cryoprotectants, vitrified, warmed, cultured and
      transferred. Abnormally fertilized oocytes were examined by electron microscopy.
      Vitrified and warmed 2-pronuclear oocytes showed 71.1% survival rate and 83.3%
      developmental rate. One- and 3-pronuclear oocytes, after cooling without
      cryoprotectants (presumably non-viable), showed progressive swelling of
      mitochondrial smooth endoplasmic reticulum (SER). After vitrification, oocytes
      (presumably viable) showed the formation of large SER vesicles associated with
      mitochondria. The described protocol of vitrification of human pronuclear oocytes
      was shown to be effective in producing pregnancy. Normal ultrastructure after
      undergoing the described vitrification protocol was confirmed.

PMID- 14567896
TI  - Frog ooplasm reverses differentiation in mammalian cells.

PMID- 14567895
TI  - Video observations on human blastocyst hatching.

PMID- 14567897
TI  - Critical evaluation of human blastocysts for assisted reproduction techniques and
      embryonic stem cell biotechnology.
AB  - Critical examination of 30 blastocysts by transmission electron microscopy (TEM)
      reveals cellular features not usually evident, including abnormalities of cell
      structure and aberrations such as multinucleation, internal fragmentation,
      phagocytic or degenerating cells. Invariably, such blastocysts are inactive and
      delay or fail to expand and hatch in vitro. Hatching seems to be a major problem
      in ageing blastocysts due to inactivity of the surface epithelium of trophoblast
      cells that do not stretch and expand. These lack surface microvilli and
      contractile tonofilaments that anchor on to specialized cell junctions such as
      desmosomes. Trophoblast expansion and consequent thinning of the zona is a
      prerequisite to proper hatching aided by the hydrostatic pressure in the
      blastocoele and by specialized cells at hatching points. Proper assessment of the
      inner cell mass is required if a healthy population of cells is to be harvested
      for embryonic stem cell culture. An inactive blastocyst is obviously not good
      material and could have a defective inner cell mass (ICM). Normally approximately
      3-5% of cells are mitotic in blastocysts and arrested cell division is also an
      indicator of inactivity. An attempt has been made to evaluate blastocyst internal
      structure for both assisted reproduction techniques and embryonic stem cell
      biotechnology.

PMID- 14567898
TI  - Mechanics of human blastocyst hatching in vitro.
AB  - Critical examination of 30 blastocysts by transmission electron microscopy at
      various stages of blastulation and hatching, has revealed the presence of
      specialized, plump, trophoblastic cells at the points of hatching, which seem to
      aid in initial breaking of the zona pellucida (ZP) and then widen its opening to
      permit the progressive emergence of the embryo in amoeboid fashion, when it
      acquires a characteristic dumb-bell shape. These cells are named 'zona-breaker'
      cells and their characteristics are described. Normally, trophoblast cells in
      expanding blastocysts are flattened (squamous), forming a continuous robust
      epithelium with specialized cell junctions. Bundles of tonofilaments anchor onto
      desmosomes, forming a terminal web. Proper expansion of blastocysts by intake of
      fluid into the blastocoele causes an increase in internal hydrostatic pressure
      that stretches the trophoblast epithelium leading to an enlargement of its volume
      two- to three-fold, consequently thinning the zona prior to hatching. This is an
      important prerequisite to normal hatching. The blastocysts usually hatch out at
      the pole opposite the inner cell mass (ICM), though a few hatch out at the
      embryonal pole or elsewhere. In all cases zona-breakers seem to play a vital role
      in the hatching process.

PMID- 14567899
TI  - Changes in T-plastin expression with human trophoblast differentiation.
AB  - During the first trimester of pregnancy, the human placenta is an actively
      dividing and highly invasive tumour-like tissue, while near term, it represents a
      fully developed, non-invasive unit. In order to understand the molecular basis of
      this marked difference in the placental phenotypes, an approach based on a
      differential display-reverse transcription-polymerase chain reaction (DD-RT-PCR)
      was adopted to analyse changes in gene expression, using total RNA isolated from
      first-trimester and term placental villi. Using this approach, T-plastin was
      initially identified as being differentially expressed in the human first
      trimester placenta. T-plastin is an actin-bundling protein and is known to be
      highly expressed in actively dividing cells and up-regulated in several
      carcinomas. Using a homogenous population of cytotrophoblasts and
      syncytiotrophoblasts isolated from human placentae, the present authors
      demonstrate the differential expression of T-plastin in cytotrophoblasts compared
      with the terminally differentiated syncytiotrophoblasts. The down-regulation of T
      plastin expression is further demonstrated in human trophoblastic BeWo cells
      induced to differentiate using transforming growth factor (TGF)beta1, a growth
      factor known for its anti-proliferative and anti-invasive response in placental
      cells. These studies suggest that expression of T-plastin in the placental
      context may indeed be associated with the enhanced replicative potential of
      placental trophoblasts.

PMID- 14567900
TI  - Development and characterization of an endometrial tissue culture system.
AB  - A culture system has been developed for pieces of whole endometrium, comprising
      many different cell types. The system maintains the integrity of all compartments
      important for tissue function and allows functional studies of the human
      endometrium. Endometrial biopsy strips were collected from fertile women. The
      strips were cut into small pieces and cultured for 8 h on dishes pre-coated with
      Matrigel. The oxygen concentration was kept low (5%), since it was shown to be
      beneficial for the culture in preliminary studies. Scanning electron microscopy
      and immunohistochemical detection of proliferating cell nuclear antigen (PCNA),
      oestrogen receptor alpha (ERalpha), progesterone receptor (PR) A + B and B and
      TUNEL were used to characterize the endometrium. During culture, the luminal and
      glandular epithelial cells began to cover the surface injured when cutting the
      sample, suggesting a healing process. The luminal epithelial surface appeared
      normal after culture. There was an increased sensitivity to culture after the
      implantation window. This new method for culture of endometrial strips in vitro
      has proven successful and may be used for functional studies of the human
      endometrium.

PMID- 14567901
TI  - Physiological implications of the materno-fetal oxygen gradient in human early
      pregnancy.
AB  - This study evaluates the role of the fetal fluid cavities on materno-fetal oxygen
      diffusion in early pregnancy. Oxygen tension (pO2) was recorded using a
      multiparameter sensor inserted inside the exocoelomic cavity (ECC) or in the
      amniotic cavity. There was no correlation between coelomic pO(2) and gestational
      age, but a negative correlation was found between amniotic pO(2) and gestational
      age. The mean (SEM) pO(2) was 19.5 mm Hg (1.83) in the ECC at 7-11 weeks and 15.4
      mm Hg (1.36) in the amniotic cavity at 11-16 weeks. The volume of the ECC changed
      little between 7 and 10 weeks of gestation, indicating that coelomic pO(2)
      results from passive oxygen diffusion through the placenta and is an indicator of
      the overall pO(2) inside the gestational sac during the first trimester. By
      contrast, the amniotic cavity volume increases exponentially, whereas amniotic
      pO(2) decreases with gestational age, suggesting that the increase in uterine
      blood flow is not sufficient to compensate for the rapid increase in amniotic
      fluid volume during the first half of pregnancy.

PMID- 14567902
TI  - Efficiency and efficacy of exogenous gonadotrophins containing LH activity.

PMID- 14567905
TI  - A randomised controlled trial to assess the impact of a package comprising a
      patient-orientated, evidence-based self-help guidebook and patient-centred
      consultations on disease management and satisfaction in inflammatory bowel
      disease.
AB  - OBJECTIVES: To determine if a whole systems approach to self-management improves
      clinical outcomes and leads to cost-effective use of NHS services. DESIGN:
      Nineteen hospitals were randomised to 10 control sites and nine intervention
      sites. Consultants from intervention sites received training in patient-centred
      care before recruitment and introduced the intervention to eligible patients.
      Patients at the control sites were recruited and went on to have an ordinary
      consultation. Qualitative interviews were undertaken to obtain an in-depth
      understanding of patients' and consultants' experience of the intervention.
      SETTING: Follow-up outpatient clinics at 19 hospitals in the north-west of
      England. PARTICIPANTS: Seven hundred patients (297 at intervention sites and 403
      at control sites) with established ulcerative colitis or Crohn's disease, aged 16
      years and over, and able to write in English. INTERVENTIONS: Consultants were
      trained to provide a patient-centred approach to care. Guidebooks on ulcerative
      colitis and Crohn's disease were developed with patients prior to the study.
      Patients prepared a written self-management plan and self-referred to services
      based on a self-evaluation of their need for advice. MAIN OUTCOME MEASURES: Rates
      of hospital outpatient consultation, quality of life (QoL) and acceptability to
      patients. Health service resource use and assessed cost effectiveness using the
      EQ-5D. RESULTS: After 1 year, the intervention resulted in fewer hospital visits,
      without change in the number of primary care visits. Patients felt more able to
      cope with their condition. The intervention produced no reduction in QoL and did
      not raise anxiety. The intervention group reported fewer symptom relapses; 74% of
      patients in the intervention group indicated a preference to continue the system.
      Qualitative results showed the guidebook was effective but organisational
      limitations constrained patient-centred aspects of the intervention for some.
      Cost-effectiveness analyses favoured self-management over standard care.
      CONCLUSIONS: Further use of this method in chronic disease management seems
      likely to improve overall patient satisfaction and reduce health expenditure
      without evidence of adverse effect on disease control. Further attention needs to
      be given to self-referral and access arrangements and a re-distribution of
      control to patients through increased adherence to patient-centred norms on the
      part of consultants. Future research is recommended to evaluate the operating
      systems within secondary and primary care that would allow self-managers to self
      refer and to keep them informed of new treatments, also to explore models for
      training health professionals in self-care methods, to study long-term effects of
      self-management in chronic disease and to transfer this approach to other chronic
      conditions.

PMID- 14567906
TI  - The effectiveness of diagnostic tests for the assessment of shoulder pain due to
      soft tissue disorders: a systematic review.
AB  - OBJECTIVES: To evaluate the evidence for the effectiveness and cost-effectiveness
      of the newer diagnostic imaging tests as an addition to clinical examination and
      patient history for the diagnosis of soft tissue shoulder disorders. DATA
      SOURCES: Literature was identified from several sources including general medical
      databases. REVIEW METHODS: Studies were identified that evaluated clinical
      examination, ultrasound, magnetic resonance imaging (MRI), or magnetic resonance
      arthrography (MRA) in patients suspected of having soft tissue shoulder
      disorders. Outcomes assessed were clinical impingement syndrome or rotator cuff
      tear (full, partial or any). Only cohort studies were included. The
      methodological quality of included test accuracy studies was assessed using a
      formal quality assessment tool for diagnostic studies and the extraction of study
      findings was conducted in duplicate using a pre-designed and piloted data
      extraction form to avoid any errors. For each test, sensitivity, specificity and
      positive and negative likelihood ratios with 95% confidence intervals were
      calculated for each study. Where possible pooled estimates of sensitivity,
      specificity and likelihood ratios were calculated using random effects methods.
      Potential sources of heterogeneity were investigated by conducting subgroup
      analyses. RESULTS: In the included studies, the prevalence of rotator cuff
      disorders was generally high, partial verification of patients was common and in
      many cases patients who were selected retrospectively because they had undergone
      the reference test. Sample sizes were generally very small. Reference tests were
      often inappropriate with many studies using arthrography alone, despite problems
      with its sensitivity. For clinical assessment, 10 cohort studies were found that
      examined either the accuracy of individual tests or clinical examination as a
      whole: individual tests were either good at ruling out rotator cuff tears when
      negative (high sensitivity) or at ruling in such disorders when positive (high
      specificity), but small sample sizes meant that there was no conclusive evidence.
      Ultrasound was investigated in 38 cohort studies and found to be most accurate
      when used for the detection of full-thickness tears; sensitivity was lower for
      detection of partial-thickness tears. For MRI, 29 cohort studies were included.
      For full-thickness tears, overall pooled sensitivities and specificities were
      fairly high and the studies were not statistically heterogeneous; however for the
      detection of partial-thickness rotator cuff tears, the pooled sensitivity
      estimate was much lower. The results from six MRA studies suggested that it may
      be very accurate for detection of full-thickness rotator cuff tears, although its
      performance for the detection of partial-thickness tears was less consistent.
      Direct evidence for the performance of one test compared with another is very
      limited. CONCLUSIONS: The results suggest that clinical examination by
      specialists can rule out the presence of a rotator cuff tear, and that either MRI
      or ultrasound could equally be used for detection of full-thickness rotator cuff
      tears, although ultrasound may be better at picking up partial tears. Ultrasound
      also may be more cost-effective in a specialist hospital setting for
      identification of full-thickness tears. Further research suggestions include the
      need for large, well-designed, prospective studies of the diagnosis of shoulder
      pain, in particular a follow-up study of patients with shoulder pain in primary
      care and a prospective cohort study of clinical examination, ultrasound and MRI,
      alone and/or in combination.

PMID- 14567907
TI  - S-nitrosylation of NSF controls membrane trafficking.
AB  - Nitric oxide is a diffusible molecule with profound effects on regulated
      exocytosis in several biological systems-however, the molecular targets remain
      elusive. In this issue of Cell, Matsushita et al. report that in aortic
      endothelial cells, S-nitrosylation of NSF, an ATPase essential for the activation
      of the membranefusion machinery, inhibits the exocytosis of Weibel-Palade bodies,
      secretory granules containing a cocktail of mediators essential to the regulation
      of vascular vessel tone.

PMID- 14567908
TI  - TSH, the bone suppressing hormone.
AB  - The skeleton is a dynamic organ whose structural integrity depends on constant
      remodeling, controlled by many local and systemic factors. In this issue of Cell,
      identify thyroid-stimulating hormone (TSH) as an important regulator of this
      process.

PMID- 14567909
TI  - The double life of ribosomal proteins.
AB  - Many integral proteins of the ribosome also carry out extra-ribosomal functions
      as independent polypeptides, raising questions as to their evolutionary
      derivation. In this issue of Cell, Mazumder et al. report a surprising new twist
      in the dual life of these molecules: as part of a cellular response to
      interferon, a large-subunit protein dramatically exits the ribosome to bind and
      inhibit the translation of a specific mRNA.

PMID- 14567910
TI  - R2D2 leads the silencing trigger to mRNA's death star.
AB  - During RNA interference (RNAi), Dicer generates short interfering RNAs (siRNAs),
      which then guide target mRNA cleavage by the RISC complex. Now, Liu et al.
      identify R2D2, a Dicer-associated protein that is important for siRNA
      incorporation into RISC, thus linking the initiation and execution phases of
      RNAi.

PMID- 14567911
TI  - Targeting survival: integration site selection by retroviruses and LTR
      retrotransposons.
AB  - Replication of retroviruses and retrotransposons depends on selecting a favorable
      chromosomal site for integration of their genomic DNA. Different retroelements
      meet this challenge by targeting distinctive chromosomal regions. Despite these
      differences, recent data hints at a common targeting mechanism-tethering of
      integration complexes to proteins bound at favorable sites.

PMID- 14567912
TI  - Nitric oxide regulates exocytosis by S-nitrosylation of N-ethylmaleimide
      sensitive factor.
AB  - Nitric oxide (NO) inhibits vascular inflammation, but the molecular basis for its
      anti-inflammatory properties is unknown. We show that NO inhibits exocytosis of
      Weibel-Palade bodies, endothelial granules that mediate vascular inflammation and
      thrombosis, by regulating the activity of N-ethylmaleimide-sensitive factor
      (NSF). NO inhibits NSF disassembly of soluble NSF attachment protein receptor
      (SNARE) complexes by nitrosylating critical cysteine residues of NSF. NO may
      regulate exocytosis in a variety of physiological processes, including vascular
      inflammation, neurotransmission, thrombosis, and cytotoxic T lymphocyte cell
      killing.

PMID- 14567913
TI  - TSH is a negative regulator of skeletal remodeling.
AB  - The established function of thyroid stimulating hormone (TSH) is to promote
      thyroid follicle development and hormone secretion. The osteoporosis associated
      with hyperthyroidism is traditionally viewed as a secondary consequence of
      altered thyroid function. We provide evidence for direct effects of TSH on both
      components of skeletal remodeling, osteoblastic bone formation, and osteoclastic
      bone resorption, mediated via the TSH receptor (TSHR) found on osteoblast and
      osteoclast precursors. Even a 50% reduction in TSHR expression produces profound
      osteoporosis (bone loss) together with focal osteosclerosis (localized bone
      formation). TSH inhibits osteoclast formation and survival by attenuating JNK/c
      jun and NFkappaB signaling triggered in response to RANK-L and TNFalpha. TSH also
      inhibits osteoblast differentiation and type 1 collagen expression in a Runx-2-
      and osterix-independent manner by downregulating Wnt (LRP-5) and VEGF (Flk)
      signaling. These studies define a role for TSH as a single molecular switch in
      the independent control of both bone formation and resorption.

PMID- 14567914
TI  - F3/contactin acts as a functional ligand for Notch during oligodendrocyte
      maturation.
AB  - Axon-derived molecules are temporally and spatially required as positive or
      negative signals to coordinate oligodendrocyte differentiation. Increasing
      evidence suggests that, in addition to the inhibitory Jagged1/Notch1 signaling
      cascade, other pathways act via Notch to mediate oligodendrocyte differentiation.
      The GPI-linked neural cell recognition molecule F3/contactin is clustered during
      development at the paranodal region, a vital site for axoglial interaction. Here,
      we show that F3/contactin acts as a functional ligand of Notch. This trans
      extracellular interaction triggers gamma-secretase-dependent nuclear
      translocation of the Notch intracellular domain. F3/Notch signaling promotes
      oligodendrocyte precursor cell differentiation and upregulates the myelin-related
      protein MAG in OLN-93 cells. This can be blocked by dominant negative Notch1,
      Notch2, and two Deltex1 mutants lacking the RING-H2 finger motif, but not by
      dominant-negative RBP-J or Hes1 antisense oligonucleotides. Expression of
      constitutively active Notch1 or Notch2 does not upregulate MAG. Thus,
      F3/contactin specifically initiates a Notch/Deltex1 signaling pathway that
      promotes oligodendrocyte maturation and myelination.

PMID- 14567915
TI  - Homeodomain interacting protein kinase 2 promotes apoptosis by downregulating the
      transcriptional corepressor CtBP.
AB  - Genetic knockout of the transcriptional corepressor CtBP in mouse embryo
      fibroblasts upregulates several genes involved in apoptosis. We predicted,
      therefore, that a propensity toward apoptosis might be regulated through changes
      in cellular CtBP. To identify pathways involved in this regulation, we screened a
      mouse embryo cDNA library with an E1A-CtBP complex and identified the homeodomain
      interacting protein kinase 2 (HIPK2), which had previously been linked to UV
      directed apoptosis through its ability to phosphorylate p53. Expression of HIPK2
      or exposure to UV irradiation reduced CtBP levels via a proteosome-mediated
      pathway. The UV effect was prevented by coexpression of kinase-inactive HIPK2 or
      reduction in HIPK2 levels via siRNA. Mutation of the residue phosphorylated by
      HIPK2 prevented UV- and HIPK2-directed CtBP clearance. Finally, reduction in CtBP
      levels, either by genetic knockout or siRNA, promoted apoptosis in p53-deficient
      cells. These findings provide a pathway for UV-induced apoptosis in cells lacking
      p53.

PMID- 14567916
TI  - Regulated release of L13a from the 60S ribosomal subunit as a mechanism of
      transcript-specific translational control.
AB  - Transcript-specific translational control is generally directed by binding of
      trans-acting proteins to structural elements in the untranslated region (UTR) of
      the target mRNA. Here, we elucidate a translational silencing mechanism involving
      regulated release of an integral ribosomal protein and subsequent binding to its
      target mRNA. Human ribosomal protein L13a was identified as a candidate
      interferon-Gamma-Activated Inhibitor of Translation (GAIT) of ceruloplasmin (Cp)
      mRNA by a genetic screen for Cp 3'-UTR binding proteins. In vitro activity of
      L13a was shown by inhibition of target mRNA translation by recombinant protein.
      In response to interferon-gamma in vivo, the entire cellular pool of L13a was
      phosphorylated and released from the 60S ribosomal subunit. Released L13a
      specifically bound the 3'-UTR GAIT element of Cp mRNA and silenced translation.
      We propose a model in which the ribosome functions not only as a protein
      synthesis machine, but also as a depot for regulatory proteins that modulate
      translation.

PMID- 14567917
TI  - Asymmetry in the assembly of the RNAi enzyme complex.
AB  - A key step in RNA interference (RNAi) is assembly of the RISC, the protein-siRNA
      complex that mediates target RNA cleavage. Here, we show that the two strands of
      an siRNA duplex are not equally eligible for assembly into RISC. Rather, both the
      absolute and relative stabilities of the base pairs at the 5' ends of the two
      siRNA strands determine the degree to which each strand participates in the RNAi
      pathway. siRNA duplexes can be functionally asymmetric, with only one of the two
      strands able to trigger RNAi. Asymmetry is the hallmark of a related class of
      small, single-stranded, noncoding RNAs, microRNAs (miRNAs). We suggest that
      single-stranded miRNAs are initially generated as siRNA-like duplexes whose
      structures predestine one strand to enter the RISC and the other strand to be
      destroyed. Thus, the common step of RISC assembly is an unexpected source of
      asymmetry for both siRNA function and miRNA biogenesis.

PMID- 14567918
TI  - Functional siRNAs and miRNAs exhibit strand bias.
AB  - Both microRNAs (miRNA) and small interfering RNAs (siRNA) share a common set of
      cellular proteins (Dicer and the RNA-induced silencing complex [RISC]) to elicit
      RNA interference. In the following work, a statistical analysis of the internal
      stability of published miRNA sequences in the context of miRNA precursor hairpins
      revealed enhanced flexibility of miRNA precursors, especially at the 5'-anti
      sense (AS) terminal base pair. The same trend was observed in siRNA, with
      functional duplexes displaying a lower internal stability (Delta0.5 kcal/mol) at
      the 5'-AS end than nonfunctional duplexes. Average internal stability of siRNA
      molecules retrieved from plant cells after introduction of long RNA sequences
      also shows this characteristic thermodynamic signature. Together, these results
      suggest that the thermodynamic properties of siRNA play a critical role in
      determining the molecule's function and longevity, possibly biasing the steps
      involved in duplex unwinding and strand retention by RISC.

PMID- 14567919
TI  - A "dock, lock, and latch" structural model for a staphylococcal adhesin binding
      to fibrinogen.
AB  - Gram-positive pathogens such as staphylococci contain multiple cell wall-anchored
      proteins that serve as an interface between the microbe and its environment. Some
      of these proteins act as adhesins and mediate bacterial attachment to host
      tissues. SdrG is a cell wall-anchored adhesin from Staphylococcus epidermidis
      that binds to the Bbeta chain of human fibrinogen (Fg) and is necessary and
      sufficient for bacterial attachment to Fg-coated biomaterials. Here, we present
      the crystal structures of the ligand binding region of SdrG as an apoprotein and
      in complex with a synthetic peptide analogous to its binding site in Fg. Analysis
      of the crystal structures, along with mutational studies of both the protein and
      of the peptide, reveals that SdrG binds to its ligand with a dynamic "dock, lock,
      and latch" mechanism. We propose that this mechanism represents a general mode of
      ligand binding for structurally related cell wall-anchored proteins of gram
      positive bacteria.

PMID- 14567920
TI  - The structure of ClpB: a molecular chaperone that rescues proteins from an
      aggregated state.
AB  - Molecular chaperones assist protein folding by facilitating their "forward"
      folding and preventing aggregation. However, once aggregates have formed, these
      chaperones cannot facilitate protein disaggregation. Bacterial ClpB and its
      eukaryotic homolog Hsp104 are essential proteins of the heat-shock response,
      which have the remarkable capacity to rescue stress-damaged proteins from an
      aggregated state. We have determined the structure of Thermus thermophilus ClpB
      (TClpB) using a combination of X-ray crystallography and cryo-electron microscopy
      (cryo-EM). Our single-particle reconstruction shows that TClpB forms a two-tiered
      hexameric ring. The ClpB/Hsp104-linker consists of an 85 A long and mobile coiled
      coil that is located on the outside of the hexamer. Our mutagenesis and
      biochemical data show that both the relative position and motion of this coiled
      coil are critical for chaperone function. Taken together, we propose a mechanism
      by which an ATP-driven conformational change is coupled to a large coiled-coil
      motion, which is indispensable for protein disaggregation.

PMID- 14567922
TI  - Hypoxic preconditioning of cardiomyocytes and cardioprotection: phophorylation of
      HIF-1alpha induced by p42/p44 mitogen-activated protein kinases is involved.
AB  - OBJECTIVE: To elucidate the molecular mechanisms involved in hypoxic
      preconditioning (HPC) of neonatal rat cardiomyocytes against
      hypoxia/reoxygenation (H/R) injury. METHODS: Cardiomyocytes from neonatal Sprague
      Dawley rats were randomly distributed into the following experimental groups: (1)
      HPC group: 20 min of hypoxia was performed to induce hypoxic preconditioning.
      Twenty four hours after HPC, cardiomyocytes were exposed to lethal hypoxia for 3
      h followed by 3 h normoxia (reoxygenation). (2) Hypoxia/reoxygenation (H/R)
      group: cardiomyocytes were directly subjected to hypoxia (3 h) followed by
      reoxygenation (3 h). (3) PD98059+HPC (PD+HPC) group: cardiomyocytes were
      preincubated with PD98059 (a selective MEK-1/2 inhibitor, 50 mumol/l) 10 min
      prior to HPC. (4) BDM+HPC group: cardiomyocytes were pretreated with an activator
      of protein phosphatase 2,3-butanedione monoxide (BDM, 20 mmol/l) 10 min prior to
      HPC. (5) Control group: cardiomyocytes were incubated in cell incubator for 30 h.
      Viability of cardiomyocytes was assessed by MTT assay. Lactate dehydrogenase
      (LDH) activity in medium was determined using a LDH assay kit. Activity of p42/44
      mitogen-activated protein kinases (p42/44 MAPKs) was detected using Western
      blotting method. SDS-PAGE mobility shift experiments were performed to determine
      phosphorylation of Hypoxia-inducible factor-1alpha (HIF-1alpha). RESULTS: HPC
      promoted survival and membrane integrity of cardiomyocytes subjected to
      subsequent sustained H/R. The protective effects of HPC were completely abolished
      either by PD98059 [a selective inhibitor of MEK-1/2 (upstream activators of
      p42/44 MAPKs)], or by BDM (an activator of protein phosphatase). Western blot
      analysis showed activated p42/44 MAPKs in whole cell extracts from hypoxic
      preconditioned cardiomyocytes. SDS-PAGE mobility shift experiments showed
      increased phophorylation level of HIF-1alpha in HPC group, and the
      phosphorylation can be blocked by PD98059 or BDM. CONCLUSIONS: HPC protects
      neonatal cardiomyocytes against H/R injury by promoting cardiomyocyte survival
      and membrane integrity. The protective mechanism might be attributed to
      upregulation of HIF-1alpha phosphorylation which may be induced by P42/44 MAPKs.

PMID- 14567923
TI  - Attenuation of homocysteine-induced endothelial dysfunction by exercise training.
AB  - Hyperhomocysteinemia is an independent risk factor for the development of
      cardiovascular disease. Exposure of endothelial cells to elevated levels of
      homocysteine (HCY) results in decreased availability of nitric oxide (NO) and
      impaired vascular function, both of which are early events in atherogenesis.
      Exercise training improves vascular function by increasing endothelial NO
      production secondary to an increase in the enzyme responsible for its synthesis,
      endothelial nitric oxide synthase (eNOS). We hypothesized that exercise training
      would increase endothelial NO production, which would attenuate the endothelial
      dysfunction associated with HCY exposure. Rats were randomly assigned to either
      sedentary (SED) or exercise (EX) groups. The exercise regimen consisted of
      treadmill running at 20-25 m/min, 15% grade, 30 min/day, 5 day/week for 6 weeks.
      Aortic rings obtained from SED and EX trained rats were incubated with 2 mM HCY
      for 120 min, then exposed to norepinephrine (NE 100 nM) to induce
      vasoconstriction. Once a stable contraction plateau was achieved, rings were
      exposed to increasing concentrations of the receptor-mediated endothelium
      dependent vasodilator acetylcholine (ACh; 0.1, 1, 10, 100 nM). This procedure was
      repeated with the non-receptor-mediated endothelium-dependent vasodilator A-23187
      (0.1, 1, 10, 100 nM), and the endothelium-independent vasodilator, NaNO(2) (0.1,
      1, 10, 100 muM). In addition, eNOS protein content and eNOS enzyme activity were
      determined. Aortic rings obtained from exercise trained rats demonstrated
      significantly (P<0.05) greater relaxation to both ACh and A-23187 in comparison
      to aortic rings obtained from SED rats following exposure to HCY. Additionally,
      exercise training increased aortic eNOS protein content and activity. Our data
      demonstrate that exercise training improves endothelium-dependent vasorelaxation
      following HCY exposure and this may be due, at least in part, to elevated levels
      of eNOS protein and an increase in eNOS activity. These results suggest the
      possible role exercise may play in attenuating the endothelial dysfunction
      associated with hyperhomocysteinemia.

PMID- 14567924
TI  - Reactive oxygen species depolymerize hyaluronan: involvement of the hydroxyl
      radical.
AB  - We have previously demonstrated that reactive oxygen species (ROS) are involved
      in cartilage degradation. A decrease in the size of hyaluronan (HA), which is the
      major macromolecule in synovial fluid and is responsible for imparting viscosity
      to it, is reported in arthritis patients. The purpose of this study is to
      determine the ROS that depolymerize HA. The luminol derivative, L-012, was used
      to determine the generation of ROS. To generate hydroxyl radicals, a mixture of
      hydrogen peroxide (H(2)O(2)) and ferrous ions (Fe(2+)) was added to HA. The
      antioxidants and the depolymerization of HA were studied in this system. The
      hydroxyl radical is one of the ROS, causing the depolymerization of HA, which
      reacts with L-01. These data suggest that hydroxyl radicals play an important
      role at the site of inflammation.

PMID- 14567926
TI  - Clinical implications of ischaemia-reperfusion injury.
AB  - Ischaemia-reperfusion injury (IRI) is a complex interplay between biochemical,
      cellular, and vascular endothelial factors. The clinical sequelae are organ
      specific, and may also involve systemic inflammatory responses. In this article,
      we outline an overview of the pathophysiology of IRI, with direct reference to
      histological and physiological changes seen in individual organs, and present the
      data on experimental methods of prevention.

PMID- 14567925
TI  - Fermented grain products, production, properties and benefits to health.
AB  - Fermented foods such as Japanese traditional food "miso (fermented soy bean
      paste)" have been shown to be rich source of micronutrients with the potential to
      prevent various human diseases. We have introduced effects of a new dietary
      supplement of fermented grain foods mixture containing extracts from wheat germ,
      soybeans, rice bran, tear grass, sesame, wheat, citrus lemon, green tea, green
      leaf extract and malted rice under the trade name of antioxidant biofactor (AOB).
      Chemical analysis of AOB shows the presence of various phenolic compounds
      (catechins, rutin, genistin, daidzin, etc.). AOB has strong antioxidant
      properties and additional biological effects, which might be of importance in
      context with the prevention of degenerative diseases. This paper focuses on the
      effect of supplementing AOB in various animal models and humans.

PMID- 14567927
TI  - Telemetrically monitored arrhythmogenic effects of doxorubicin in a dog model of
      heart failure.
AB  - A model of chronic heart failure has been induced in dogs by repeated
      intracoronary infusion of doxorubicin, which is an antineoplastic medication that
      has dose-limiting cardiotoxic side effects. Although many of the dogs receiving
      doxorubicin develop typical signs of dilated cardiomypathy over 4-6 weeks, some
      of them suddenly die before completing the four weekly infusions of the drug. The
      present study was undertaken to determine whether such sudden death may be caused
      by the development of fatal arrhythmias during doxorubicin treatment. This was
      assessed by telemetrically monitoring the EKG of seven dogs, which received
      intracoronary infusion of 1 mg/kg doxorubicin given in four divided weekly doses.
      The recordings were obtained for 8-10 h on alternate days up to 4 weeks. Echo
      cardiographic recordings were obtained once a week. The acute effects with each
      infusion of doxorubicin included a significant increase in heart rate, and no
      significant change in QRS complex. The cumulative prolonged effects of
      doxorubicin included slight reduction in QRS amplitude and duration, and marked
      arrhythmic changes. Four out of seven dogs showed a spectrum of arrhythmic events
      such as single or groups of premature ventricular complexes (PVCs), bigeminy,
      ventricular tachycardia (VTAC), ventricular fibrillations (VFIB), and asystole.
      All dogs did not show each of the events listed above and the same dog did not
      show all the events all the time. One of these four dogs developed VFIB for 25
      min and then asystole leading to sudden death. These studies conclusively showed
      that fatal arrhythmias develop in some of the dogs receiving doxorubicin
      treatment accounting for the sporadic incidence of sudden death. Prophylactic
      treatment with antiarrhythmic agents may prevent such adverse events.

PMID- 14567928
TI  - Effect of endothelin receptor antagonist bosentan on plasma leptin concentration
      in acute myocardial infarction in rats.
AB  - The aim of the study was to evaluate the effect of endothelin receptor antagonism
      on plasma leptin level after myocardial infarction (MI). In Wistar rats under
      chloral hydrate anesthesia, MI was performed by ligation of the left coronary
      artery. The animals were divided into the following groups: control-sham
      (thoracotomy only), and two MI groups with or without bosentan treatment.
      Bosentan was given daily by gavage at the dose of 100 mg/kg. Treatment of animals
      started 2 days before MI and continued up to the fifth day. Concentration of
      leptin was measured by radioimmunoassay by means of 125I labeled antigen in the
      following time intervals: before MI or sham operation, 4, 24 and 48 h after
      surgery. Electrocardiogram (ECG), blood pressure, heart rate, arterial pO(2),
      pCO(2) and pH were periodically monitored. Two days after the MI animals were
      perfused retrograde into descending aorta with 2% triphenyltetrazolium chloride
      (TTC) and hearts were fixed by immersion in formalin for microscopic examination.
      Hearts were sectioned transaxially and size of MI was quantitated with
      morphometric methods. ECG, TTC staining and microscopic results confirmed
      development of MI. Morphometric methods did not show significant differences in
      infarct size between bosentan treated and untreated groups. Concentration of
      leptin in plasma in untreated group significantly increased already 4 h after MI.
      In bosentan treated animals this increase appeared only after 24 h. In animals
      treated with bosentan also a significant diminution of MI mortality was observed.
      Our results indicate that bosentan has an important effect on leptin
      concentration in ischemic cardiovascular pathology.

PMID- 14567929
TI  - Garlic attenuates hypercholesterolemic risk factors in olive oil fed rats and
      high cholesterol fed rats.
AB  - This study was undertaken to compare the effects of garlic (G) on
      hypercholesterolemic risk factors in rats fed with corn oil (C) or olive oil (O)
      with and without cholesterol (Ch) enrichment in the diet. Male Sprague-Dawley
      rats (n=6 per group) were fed semi-purified diets containing 5% oil with or
      without cholesterol (Ch) or garlic (G) for 21 days. In the C fed rats, addition
      of dietary Ch, there was a redistribution of Ch from HDL to LDL class. In
      contrast, 1% Ch added to O diets produced a 4-fold increase in serum Ch compared
      with levels in rats fed O without Ch. This was associated with a 14-fold increase
      in LDL Ch and a 7-fold decrease in HDL Ch levels. Addition of 2% G had no effect
      on the distribution of serum Ch between HDL and LDL Ch in C+Ch fed rats, but in
      O+Ch fed rats, G halved the increase in serum Ch and LDL and attenuated the
      decrease in serum HDL by 23%. The results suggest that the dietary O regulated
      the levels of serum in Ch loaded rats. G attenuated serum Ch in O fed rats and
      decreased serum risk factors, both total Ch and LDL-C ratio and LDL-Ch/HDL-Ch
      ratio.

PMID- 14567930
TI  - Stress and the immune system.
AB  - Stressors can positively or adversely affect immune and inflammatory responses.
      However, the current understanding of these effects at the cellular and molecular
      levels is not sufficient to allow prediction of the effects of a particular
      stressor on a particular immune or inflammatory function. Three complementary
      conceptual frameworks are presented that may prove useful in developing such an
      understanding. In addition, specific examples of the action of particular stress
      mediators on particular immune or inflammatory end points are discussed, and the
      relationship of these observations to the conceptual frameworks is indicated.
      Several of the effects discussed are relevant clinically, and the prospects for
      pharmacological intervention to prevent adverse effects of stressors on the
      immune system are discussed. Finally, some of the factors that can (sometimes
      unexpectedly) influence the outcome of stress-immunology studies and some of the
      pitfalls that continue to make this area of research controversial in some
      circles are discussed.

PMID- 14567931
TI  - Computer use related upper limb musculoskeletal (ComRULM) disorders.
AB  - Computer use has progressed fast in recent years. The symptoms and signs caused
      by repetitive computer use that is characterized by neck, shoulder, elbow, wrist
      and hand pain, paresthesia, and numbness can be called 'Computer Related Upper
      Limb Musculoskeletal (ComRULM) disorders'. Publications of recent 20 years have
      been reviewed. These disorders are usually multifactorial processes, caused by
      occupational, personal and social factors. Some suggestions concerning the
      diagnostics, procedures of prevention, and treatment options have been discussed.
      Further studies on 'ComRULM disorders' are necessary.

PMID- 14567932
TI  - Pathogenesis of various forms of infection in artificial hearts.
AB  - Implanted biomaterials are often inevitably attacked by the bacterial infection.
      So far this problem has not been sufficiently explained and solved. It represents
      an 'evergreen' in the artificial heart research. Infection of biomaterials is a
      completely new clinical entity that profoundly differs from the common clinical
      course of various kinds of infections and their treatment. These infections are
      persistent; they resist host defense mechanisms and antibiotic therapy because
      the nature of these microorganisms has changed due to their protection by the
      biofilm of some bacteria on the surfaces of implanted biomaterials. In our 66
      long-term experiments with total artificial heart (TAH) in 25 animals, the
      infection and sepsis were the main causes of death. The different organs,
      attacked by the bacterial and septic complications, varied from case to case as
      the predominant organs, the function of which ceased to be compatible with
      further survival. The main foci where the infection started were also very
      variable. The artificial hearts used in these 25 calves were predominantly of TNS
      BRNO-VII type (19 animals), TNS-BRNO-II type (4 animals) and of ROSTOCK TAH type
      (2 animals). The decrease of the immune defense in the TAH recipients of
      different intensity was evident during the course of infectious process and
      simultaneously, the virulence and resistance of the microorganisms against
      antibiotics substantially increased. The activity of the infectious agents was
      often combined with increased blood coagulation and thrombi formation. In 5
      calves hemolytic and hemorrhagic episodes were observed, and in 15 calves without
      simultaneous anti-calcification treatment, a primary calcification of driving
      diaphragms was observed. A common dystrophic calcification sometimes complicated
      septic thrombogenesis. The tactics of the antibiotic therapy differed according
      to the results of hemocultivation tests and body temperature and was often
      supported by the stimulation of the immune resistance. In 2 cases we used the
      coating of blood chamber and driving diaphragm with albumin and hydrophilic
      polyurethane in order to show whether this changed surface will influence
      positively or negatively the bacterial seeding on the biomaterial surface. We
      assume the infections in the TAH recipients to be a multi-factorial process, and
      therefore the prevention and therapy ought to be also multi-factorial. We tried
      to respect this approach and we were able to increase the survival from 39 to 293
      days.

PMID- 14567934
TI  - Efficacy of a half dose of oral pyridostigmine in the treatment of chronic
      fatigue syndrome: three case reports.
AB  - Chronic fatigue syndrome (CFS) is characterized by persistent mental and physical
      fatigue for at least 6 months. Its pathophysiology is unknown and there is no
      proven effective treatment. We describe three cases who fulfill the criteria of
      CFS, in whom a defect of neuromuscular transmission and dysautonomia are present
      and who respond to acetylcholine-esterase inhibition. Case 1: 18-year-old female
      with a 3-year history of CFS. Response of compound-muscle-action potential,
      recorded using surface recording electrode, over left abductor pollicis brevis
      muscle, to repetitive nerve stimulation (RNS) at a rate of 10 Hz showed a 42%
      incremental response. Composite autonomic scoring system (CASS) showed mild
      cholinergic impairment (cardiovagal score: 1; sudomotor score: 2). Serological
      tests for Epstein-Barr virus (EBV) revealed positive antiviral capsid antigens
      (anti-VCA) immunoglobulins G (IgG). Oral pyridostigmine therapy (30 mg) resulted
      in marked improvement in symptoms. Case 2: 28-year-old female with 10-year
      history of CFS. RNS, using identical protocol, showed a 60% incremental response
      over the same muscle. CASS showed mild cholinergic impairment (cardiovagal score:
      1; sudomotor score: 2) and this patient was also positive for EBV. This patient
      responded dramatically to 10-mg pyridostigmine. Case 3: 29-year-old female with a
      history of CFS for longer than 15 years. Repetitive stimulation, using identical
      paradigm to left abductor pollicis brevis muscle, showed a 42% incremental
      response. CASS showed mildly cholinergic impairment (cardiovagal score: 2;
      sudomotor score: 1). EBV antibody titers were positive. Patient responded to 30
      mg pyridostigmine with an improvement in her fatigue. These three cases generate
      the hypothesis that the fatigue in some patients with clinical CFS might be due
      to a combination of mild neuromuscular transmission defect combined with
      cholinergic dysautonomia. Support for this thesis derives from the improvement
      with cholinesterase inhibition.

PMID- 14567933
TI  - Melatonin protects against ischemia-reperfusion injury and inhibits apoptosis in
      isolated working rat heart.
AB  - INTRODUCTION: Melatonin (MEL), a pineal hormone, is well known as a potent
      antioxidant in a variety of ischemia-reperfusion models. Recent studies have
      assumed a pivotal role of reactive oxygen species (ROS) in the development of
      apoptosis. There are few pieces of information concerning a possible protective
      role of MEL against apoptosis in ischemia-reperfusion injury of myocardium.
      METHODS: We conducted an in vitro experiment: (1) to study the effect of MEL in
      the model of isolated and perfused working rat heart; (2) to evaluate the
      antioxidant capacity of MEL by a simple fluorescence test; and (3) to analyze the
      extent of apoptosis inhibition by MEL. Four groups of male Wistar rat were used:
      (a) group 'MEL 50 muM' (n=8); (b) group 'ischemia 30 min' (n=8); (c) group
      'controls' (n=8); and (d) group 'controls+MEL 50 muM' (n=8). The perfusion medium
      was an oxygenated Krebs-Henseleit buffer (KHB). Hearts in groups (a) and (b)
      underwent 30 min of global normothermic ischemia and 45 min of reperfusion; 3 min
      before ischemia the hearts of group (a) received KHB with MEL 50 muM (and MEL 50
      muM was also present in KHB solution during reperfusion). Hearts of group (c)
      were only perfused by KHB, and hearts of group (d) perfused by KHB+MEL 50 muM
      throughout the experiment. Registered were basic hemodynamic parameters:
      coronary, aortic, cardiac output and heart rate. At the end of each experiment, a
      left ventricle samples were taken for in situ detection of apoptosis using a
      TUNEL in-situ detection kit (POD) and quantitative analysis was performed.
      Malonedialdehyde concentrations were evaluated from heart homogenate to determine
      the severity of oxidative damage. To study the antioxidant capacity of MEL, a
      fluorescence test with allophycocyanin as an indicator was performed. A peroxyl
      radical generator, 2,2'-azobis(2-amidinopropan)-4-hydrochloride (AAPH) was used,
      and the antioxidant effect of MEL was expressed in oxygen-radical absorbing
      capacity (ORAC) units. RESULTS: Treatment by MEL resulted in a significant
      improvement of hemodynamic parameters and reduction of postischemic arrhythmias
      during reperfusion. All hearts in group 'ischemia 30 min' developed fatal
      ventricular fibrillations. MEL significantly reduced the incidence of apoptotic
      cells (14+/-4.3%; **P<0.01) vs. group 'ischemia 30 min' (58+/-2.1%). No apoptotic
      cells were detected in both control groups (c) and (d). In the fluorescence test,
      MEL exhibited a significant dose-dependent protective effect against peroxyl
      radical; MEL also reduced significantly the level of lipoperoxidation (MDA;
      *P<0.05). Analysis of hemodynamic parameters in both control groups (c) and (d)
      did not show any significant differences; the presence of MEL 50 muM in KHB
      solution did not have any important influence on cardiac performance in this type
      of experiment. CONCLUSION: We confirmed the previously reported beneficial
      effects of MEL against ischemia-reperfusion injury, presumably via its
      antioxidant properties. A significant suppression of apoptosis and the peroxyl
      radical scavenging properties of MEL in our study could contribute to the
      hypothesis of a close link between oxidative stress and apoptosis promotion.

PMID- 14567935
TI  - Rolipram, a specific type IV phosphodiesterase inhibitor, ameliorates
      indomethacin-induced gastric mucosal injury in rats.
AB  - Inhibition of type IV phosphodiesterase activity is beneficial in various
      inflammation mediated by its function to suppress the production of inflammatory
      cytokines in inflammatory cells. Nonsteroidal anti-inflammatory drugs (NSAIDs)
      such as indomethacin are well known to develop gastric mucosal lesion. As
      pathogenesis of indomethacin induced gastric mucosal lesion, activation of
      neutrophils and inflammatory cytokine production play critical roles. However,
      the effect of phosphodiesterase inhibitors on development of gastric mucosal
      lesion has not been reported. In the present study, we examined the effect of
      specific type IV phosphodiesterase inhibitor (rolipram) on NSAIDs-induced gastric
      mucosal lesion. Also, we examined the effect of rolipram on tissue prostaglandin
      E2 (PGE2) production. Indomethacin-induced gastric mucosal injury was produced by
      the intragastric administration of indomethacin (30 mg/kg). Rolipram was injected
      to the rats intraperitoneally 30 min before the indomethacin administration.
      Ulcer index and tissue myeloperoxidase (MPO) activity of the gastric mucosa was
      evaluated. The gastric concentration of PGE2 was determined by RIA. Gastric
      mucosal lesion induced by indomethacin was significantly inhibited with treatment
      of rolipram. Mucosal MPO activity was also suppressed by administration of
      rolipram. Gastric mucosal PGE2 concentration was not affected by intraperitoneal
      injection of rolipram. Based on these data, the beneficial effects of rolipram on
      indomethacin-induced gastric mucosal injury may be attributed to its anti
      inflammatory properties.

PMID- 14567936
TI  - Signal transduction pathways in cerebral vasospasm.
AB  - Cerebral vasospasm is a deadly complication following the rupture of intracranial
      aneurysms. The time course of cerebral vasospasm is unique in that it is slow
      developing, usually takes 4-7 days to peak, but lasts up to 2-3 weeks, and is
      resistant to most known vasodilators. These special features make cerebral
      vasospasm the most important determinant in the outcome of patients suffering
      subarachnoid hemorrhage. The available treatment strategies include mechanical
      dilation of spastic cerebral arteries (angioplasty) and non-selective
      vasodilatation such as by Ca(2+) channel blockers. One new development in the
      experimental treatment of cerebral vasospasm is the looming target of signaling
      pathways. Understanding vasospastic signals in cerebral arteries might offer a
      new avenue for selective treatment of cerebral vasospasm in the future.

PMID- 14567937
TI  - Endothelial cell activation in inflammation: lessons from mutant mouse models.
AB  - Dysregulation of the inflammatory response is a causative or contributing factor
      in many cardiovascular pathologies. Molecular mechanisms involved in these
      processes indicate that the vascular endothelium is an important facet in the
      regulation of inflammation. Gene targeted mutational studies in the mouse have
      shown that adhesion and signaling molecule expression within the endothelium
      participate in the pathogenic process of cardiovascular disease. These studies
      provide insight into genetic pathways that may be therapeutically relevant in
      both treatment and diagnostic regimens. However, we have also learned that the
      role of these pathways in endothelium during inflammatory diseases is complex,
      requiring further study to better understand specific mechanisms involved in
      endothelial cell dysfunction during cardiovascular disease. Alternative gene
      targeting techniques, such as the Cre-loxP system, are beginning to allow tissue
      specific investigation of genetic pathways within the endothelium; however,
      extensive use of this technology is limited. This review discusses the role of
      the endothelium during inflammation and the insights that have been gained from
      the use of gene targeted mutant mice.

PMID- 14567938
TI  - Retrospective investigation on management of salivary hypofunction concerning
      with serum zinc content.
AB  - Monthly measurement of the resting saliva was performed in addition to
      psychosomatic therapy for patients visiting our clinic who were suspected of
      having decreased activity of carbonic anhydrase. According to the serum zinc
      content, patients were divided into a low serum zinc group (n=22) and a mid-high
      serum zinc group (n=12). Patients in the former group were advised to improve
      mastication efficiency and to consume more food with a high zinc content. After
      6.6+/-5.6 months, serum zinc increased from 75.6 to 90.9 mug/dl in the former
      group, whereas no change was found in the latter group, though symptoms improved
      in the both groups. Improvement in salivary secretion was noticed in DeltapH(I)
      in the former group, and a decrease in K(+) concentration was found in the latter
      group.

PMID- 14567939
TI  - Topical oxygen as an adjunct to wound healing: a clinical case series.
AB  - BACKGROUND: Disrupted vasculature and high energy-demand to support processing
      and regeneration of wounded tissue are typical characteristics of a wound site.
      Oxygen delivery is a critical element for the healing of wounds. Clinical
      experience with adjunctive hyperbaric oxygen therapy in the treatment of chronic
      wounds have shown that wound hyperoxia increases wound granulation tissue
      formation and accelerates wound contraction and secondary closure. Nevertheless,
      the physiologic basis for this modality remains largely unknown. Also, systemic
      hyperbaric oxygen therapy is associated with risks related to oxygen toxicity.
      Topical oxygen therapy represents a less explored modality in wound care. The
      advantages of topical oxygen therapy include low cost, lack of systemic oxygen
      toxicity, and the ability to receive treatment at home, making the benefits of
      oxygen therapy available to a much larger population of patients. MATERIALS AND
      METHODS: Over 9 months, seven surgeons treated 58 wounds in 32 patients with
      topical oxygen with follow-up ranging from 1 to 8 months. The data presented
      herein is a retrospective analysis of the results we have achieved using topical
      oxygen on complex wounds. RESULTS: Thirty-eight wounds in 15 patients healed
      while on topical oxygen. An additional five wounds in five patients had
      preoperative oxygen therapy; all wounds initially healed postoperatively. In two
      patients, wounds recurred post-healing. In ten wounds, topical oxygen had no
      effect; and two of those patients went on to require limb amputation. There were
      no complications attributable to topical oxygen. Three patients died during
      therapy and one died in the first postoperative month from underlying medical
      problems. Two patients were lost to follow-up. CONCLUSIONS: In this case series,
      topical oxygen had no detrimental effects on wounds and showed beneficial
      indications in promoting wound healing.

PMID- 14567940
TI  - Anti-inflammatory effect of Pelteobagrus nudiceps extract on rat model of CFA
      induced pulmonary tuberculous granuloma.
AB  - We investigated the effectiveness of supportive therapy with a fish-oil extract
      called repair tuberculosis (RTB) in anti-tuberculosis treatment, and the
      underlying mechanism of action. The active component of RTB is the unsaturated
      fatty acid docosatetraenoic acid (C(22)H(36)O(2)), which was reported to induce
      the resorption and healing of pulmonary lesions in patients with severe pulmonary
      tuberculosis. We administered RTB to a rat model of CFA-induced pulmonary
      tuberculous granuloma (RTB group), and compared the results with those in a
      control group, which did not receive RTB. Histological examination of the lungs
      showed a significantly smaller area of granuloma in the RTB group than in the
      control group. IFN-gamma levels in bronchoalveolar lavage fluid (BALF) were
      higher in the RTB group than in the control group, suggesting that Th1-type
      immune reaction is activated in the RTB group. Moreover, significantly enhanced
      expression of inducible nitric oxide synthase mRNA in lung tissue was observed in
      the RTB group. Superoxide production by cells recovered from BALF was attenuated
      in the RTB group. There were no difference in IL-4 levels in BALF, or in
      expression of TNF-alpha mRNA in lung tissue between the RTB and control groups.
      The above results suggest that RTB activates Th1-type cellular immune reaction,
      promotes absorption of lesions, and inhibits the generation of cytotoxic
      substances.

PMID- 14567941
TI  - Role of the endothelium in the vascular effects of vitamin C in rats.
AB  - The present study was undertaken to determine whether vascular responsiveness and
      endothelial function were altered in rats after 8 weeks of vitamin C treatment.
      Thoracic aortae were isolated from control and vitamin C-treated rats and
      analysed for changes in vascular reactivity. Vitamin C treatment attenuated the
      contractile response of aortic rings to noradrenaline and KCl. Removal of the
      endothelium increased the sensitivity of control rings but did not alter the
      effect of vitamin C. Endothelium-dependent relaxation to acetylcholine was
      significantly (P<0.05) enhanced by vitamin C, but the endothelium-independent
      relaxation response to sodium nitroprusside was not affected by vitamin C. The
      results suggest that the endothelium is not involved in the reduction in vascular
      sensitivity to contractile agonists caused by vitamin C. In addition, the
      enhancement of endothelium-dependent relaxation may be due to protection of
      nitric oxide against inactivation by oxygen free radicals.

PMID- 14567942
TI  - Suppression of the release of type-1 plasminogen activator inhibitor from human
      vascular endothelial cells by Hawaii deep sea water.
AB  - The effect of deep sea water on the fibrinolytic properties of human vascular
      endothelial cells was investigated. There was no difference in the growth ratio
      between human umbilical vein endothelial cells (HUVECs) cultured with growth
      medium (RPMI-1640 containing 20% fetal calf serum) prepared with Hawaii deep sea
      water (HDSW medium) and those with medium prepared with normal distilled water
      (control medium). The secretion of type 1 plasminogen activator inhibitor (PAI-1)
      from HUVECs was significantly reduced by about twofold. However, the levels of
      PAI-1 mRNA in HUVECs cultured with HDSW medium did not change when compared with
      those cultured with control medium. Though HDSW medium also reduced the secretion
      of tissue-type plasminogen activator, the suppressive effect was more prominent
      for PAI-1. Thus, the balance of fibrinolytic activity was turned toward anti
      thrombotic in HUVECs. This was evidenced by the lysis of 125I-fibrin clot in the
      presence of plasminogen. That is, HUVECs cultured with HDSW medium degraded 125I
      fibrin more efficiently than HUVECs with control medium. Such enhanced clot lysis
      was maintained as long as HDSW medium was present. The accelerated effect of HDSW
      medium on clot lysis disappeared after the exchange of HDSW medium to control
      medium. These findings suggest that HDSW may specifically and predominantly
      affect the process of molecular transfer of PAI-1 after its transcription,
      resulting in an enhanced fibrinolytic activity of HUVECs. Since HDSW reduces the
      thrombotic potential of cultured HUVECs, it is speculated that the materials
      contained in HDSW may prevent the incidence of thrombotic disorders.

PMID- 14567943
TI  - Effect of clinical clerkship on students' attitudes toward medical learning in
      Japan: a case study at Kinki University School of Medicine.
AB  - A 20-item questionnaire was administered to 253 physicians and 111 medical
      students, who did not have previous clinical clerkship experience, upon
      completion of their clinical clerkship. Medical students responded that they
      enjoyed their clinical clerkships but felt pressured and physically tired. Ninety
      percent of these medical students developed expectations for their career choice
      during their clinical clerkship. Only 18% of physicians felt that they allowed
      students enough chance to participate in clinical practice. We must emphasize
      that the success of any clinical clerkship system depends on an effective
      communication system between physicians and medical students.

PMID- 14567944
TI  - Biochemical entities that influence membrane-associated TNF RII (80-kDa) and IL-1
      RI (80-kDa) complex expression and receptor fragment production in adherent
      vascular endothelium.
AB  - The research aim of the present investigation was to identify leukocyte enzyme
      proteases that have the capacity to biochemically recruit the passive
      participation of vascular endothelium in cytokine receptor 'shedding' phenomenon
      involving membrane-associated TNF RII (80-kDa) and IL-1 RI (80-kDa) complexes.
      Achieving this research objective involved the design of a laboratory approach
      that delineated to what extent enzyme-proteases released by activated macrophages
      directly interact with, and liberate soluble fragments of membrane-associated
      cytokine receptor complexes. Results from this segment of the investigation
      revealed that cathepsin-D, a leukocyte carboxyl/aspartate protease, altered the
      integrity and generated soluble fragments of TNF RII (80-kDa) and IL-1 RI (80
      kDa) receptor complexes expressed by vascular endothelium. Furthermore,
      laboratory findings also suggested that cathepsin-D possessed the ability to
      variably deplete biologically functional membrane-associated TNF RII (80-kDa) and
      IL-1 RI (80-kDa) complexes. Complementary investigations isolated a
      carboxyl/aspartate protease from activated macrophages utilizing pepstatin-A
      affinity chromatography. Exposure of vascular endothelium to pepstatin-A binding
      proteins resulted in a detectable depletion of membrane-associated TNF RII (80
      kDa) and IL-1 RI (80-kDa) in addition to the generation of soluble receptor
      fragments. Analysis of macrophage pepstatin-A binding proteins by SDS-PAGE
      identified a primary fraction with a molecular mass of 47-52-kDa that closely
      correlated with the known molecular mass of leukocyte cathepsin-D. Evaluation of
      macrophage pepstatin-A binding-protein fractions by non-denaturing Hb-PAGE
      detected a lucent proteolytic band at 47-52-kDa compatible with the known
      molecular mass of leukocyte cathepsin-D. Macrophage pepstatin-A binding proteins
      also hydrolyzed a synthetic enzyme-specific substrate that selectively recognizes
      cathepsin-D biochemical activity. In conclusion, the leukocyte carboxyl/aspartate
      protease, cathepsin-D can biochemically alter the integrity and generate soluble
      fragments of membrane-associated TNF RII (80-kDa) and IL-1 RI (80-kDa) receptor
      complexes expressed by vascular endothelium. The relevance of this concept is in
      part based on investigations that have discovered that genetic 'knock-out' mice
      incapable of expressing IL-1 RI (80-kDa) or TNF RI (55-kDa) receptor complexes
      are highly resistant to developing the pathophysiological alterations classically
      associated with conditions of endotoxic-shock.

PMID- 14567945
TI  - Investigation of unsaturated water flow in a deep vadose zone by applying quasi
      partition law to 222Rn.
AB  - This paper describes an application of the quasi-partition law of radon-222
      (222Rn) to a deep unsaturated vadose zone in a field. 222Rn is a very useful
      tracer to investigate not only saturated but also unsaturated water flows in
      vadose zones. Concentrations of 222Rn in water in unsaturated soils are, based on
      the quasi-partition law, lower than those in saturated soils. However, no study
      has previously applied quasi-partition law of 222Rn to analyze saturated and
      unsaturated water flows in vadose zones. In this study, we observed the
      applicability of existing theoretical equations of quasi-partition law of 222Rn
      experimentally. After confirming the validity of the theoretical equation, we
      applied this equation to estimate the unsaturated water flow in an actual vadose
      zone. By comparing the estimated degree of saturation from 222Rn measurement with
      that from a neutron moisture meter measurement, we obtained a beautiful agreement
      between them.

PMID- 14567946
TI  - Assessment of the radiological impacts of historical coal mining operations on
      the environment of Ny-Alesund, Svalbard.
AB  - Mineral extraction activities, such as those conducted by oil, gas and coal
      industries, are widespread throughout the Arctic region. Waste products of these
      activities can result in significant contributions to the radioactive burden of
      the surrounding environment due to increased concentrations of naturally
      occurring radioactive materials (NORM) to levels that would not normally be found
      in the environment. Coal mining operations commenced in the early 1900s on
      Svalbard and have been conducted at a variety of locations on the archipelago
      since then. Coal contains radionuclides of the uranium and thorium series as well
      as 40K. Extraction and processing of coal can result in releases of these
      radionuclides to the broader environment with subsequent impact on the human and
      non-human inhabitants of the area. This paper presents the results of a study on
      environmental radioactivity resulting from historical coal mining operations
      conducted at Ny-Alesund, Spitsbergen, in the Svalbard archipelago. Activity
      concentrations of radionuclides found in materials associated with these
      operations are presented as well as the results of a spatial dosimetric survey
      conducted over an area affected by coal mining.

PMID- 14567947
TI  - 238Pu, 239,240Pu, 241Am, 90Sr and 137Cs in soils around nuclear research centre
      Rez, near Prague.
AB  - Forty-four soil samples were taken around the nuclear research centre Rez, near
      Prague. The mean activity concentrations of 238Pu, 239,240Pu, 241Am, 90Sr and
      137Cs in uncultivated soil were 0.010, 0.26, 0.12, 2.7 and 23 Bq.kg(-1),
      respectively. Contents of radionuclides in cultivated soil were lower and in
      forest soil higher than in uncultivated soil. The mean activity ratios of
      238Pu/239,240Pu, 241Am/239,240Pu, 90Sr/239,240Pu and 239,240Pu/137Cs in
      uncultivated soil were 0.041, 0.47, 10.9 and 0.013, respectively. The mean
      activity ratios in cultivated and forest soils were close to the values given
      above. It follows from the results that the source of 239,240Pu, 90Sr and 137Cs
      in the studied area is deposition from atmospheric nuclear tests, in the case of
      137Cs also deposition from Chernobyl accident. The contribution of the research
      centre effluents was not proved for these radionuclides. Increased activity ratio
      of 241Am/239,240Pu indicates the presence of 241Am in the soils studied emanating
      from sources other than nuclear tests. Uniform distribution of the
      241Am/239,240Pu activity ratio around the nuclear research centre and the absence
      of an area with evidently higher activity ratio, including at sites lying in the
      main wind direction, suggest that the additional activity of 241Am does not
      originate from the nuclear research centre. The additional source might be the
      deposition following the Chernobyl accident.

PMID- 14567948
TI  - Radiocaesium soil-to-plant transfer in tropical environments.
AB  - In this work, soil-to-plant transfer factors of radiocaesium are predicted based
      on soil properties such as pH, organic matter content, exchangeable K+ and clay
      content valid for the tropical environments in Bangladesh, China and Japan, and
      using a previously published model. Due to insufficient data of soil properties
      in the selected regions, the average values of pH, organic matter content,
      exchangeable K+ and clay content were taken as the input model parameters within
      the ranges given for Asia. Nevertheless, a complete set of soil properties of
      Japanese soils was used to compare the measured and calculated TF values of
      radiocaesium for radish. The calculated TF values for radiocaesium are comparable
      with the measured values especially for leafy parts of a plant. However,
      calculated values for rice, an important crop in Asia are found to overestimate
      the measured values due to an overestimate of calculated CECs in soils in the
      selected regions. The empirical parameters used in the model need to be re
      evaluated for the specific part of a plant and/or for a variety of different
      plants. Alternatively, a general conversion factor for each part of a plant
      and/or for a variety of different plants for a specific region is suggested for
      tropical environments.

PMID- 14567949
TI  - Conversion factors for external gamma dose derived from natural radionuclides in
      soils.
AB  - Field in situ gamma radiation exposure rates and laboratory measured
      radioactivity contents of 1500 Spanish soils were compared. The main objective
      was to determine if published theoretically derived conversion factors would
      yield accurate quantitative activity concentration (Bq kg(-1)) for the data
      carried out in different surveys developed by our laboratory during the last ten
      years. The in situ external gamma dose rate results were compared to laboratory
      gamma analysis of soils samples gathered from each site, considering the
      concentrations of seven radionuclides: 40K, 214Pb, 214Bi, 212Bi, 212Pb, 208Tl and
      228Ac. The coefficient of correlation found between these variables indicate a
      good relationship. A discussion of the factors contributing to the uncertainties
      as well as measurement procedure are also given in this paper.

PMID- 14567950
TI  - Characterization of an underground site in Northern Italy in view of low
      radioactivity measurements.
AB  - A low background station for the measurement of low level radioactivity is under
      development in Northern Italy. The rock cover is about 300 m water equivalent. We
      report and discuss measurements of radon concentration in air and of gamma, muon
      and neutron fluxes performed in the neighborhood of the station site. We present
      and apply a simple analytical model capable to disentangle the contribution to
      the measured gamma activities due to 222Rn in air from the one due to 238U and
      its daughters in the rocks.

PMID- 14567951
TI  - A simple bubbling system for measuring radon (222Rn) gas concentrations in water
      samples based on the high solubility of radon in olive oil.
AB  - Based on the different levels of solubility of radon gas in organic solvents and
      water, a bubbling system has been developed to transfer radon gas, dissolving
      naturally in water samples, to an organic solvent, i.e. olive oil, which is known
      to be a good solvent of radon gas. The system features the application of a fixed
      volume of bubbling air by introducing a fixed volume of water into a flask
      mounted above the system, to displace an identical volume of air from an air
      cylinder. Thus a gravitational flow of water is provided without the need for
      pumping. Then, the flushing air (radon-enriched air) is directed through a vial
      containing olive oil, to achieve deposition of the radon gas by another bubbling
      process. Following this, the vial (containing olive oil) is measured by direct
      use of gamma ray spectrometry, without the need of any chemical or physical
      processing of the samples. Using a standard solution of 226Ra/222Rn, a lowest
      measurable concentration (LMC) of radon in water samples of 9.4 Bq L(-1) has been
      achieved (below the maximum contaminant level of 11 Bq L(-1)).

PMID- 14567952
TI  - Foliar uptake of 134Cs and 85Sr in strawberry as function by leaf age.
AB  - In this paper a study of the foliar uptake and translocation of 134Cs and 85Sr in
      a herbaceous fruit plant is presented. In particular, absorption, translocation
      and loss of these radionuclides in strawberry plants have been studied in
      relation to the age of contaminated leaves. Strawberry plants were contaminated
      by distributing droplets of an aqueous solution containing 134CsCl and 85SrCl2 on
      the surface of two leaves per plant. One half of the plants was contaminated
      through two young leaves, a second half through two old leaves. Sets of plants
      were collected 1 day, 7 days and 15 days after contamination. One half of them
      was rinsed with double distilled water before gamma analysis. Rinsing
      contaminated leaves removes on average 55% of the applied 134Cs and 45% of 85Sr.
      The activity removed decreases during the 15 days of the experimental study, both
      for 134Cs and for 85Sr, suggesting an increase in foliar absorption during this
      period. The activity removed does not differ between old and young leaves.
      "External loss" is lower for young than old contaminated leaves. "Internal loss"
      through translocation occurs mainly for 134Cs. Translocation coefficients from
      contaminated leaves to fruits are two orders of magnitude higher for 134Cs
      (4.0%), than for 85Sr (0.05%). Leaf to fruit translocation coefficients for 134Cs
      are higher from young leaves (5.8%), than from old leaves (2.3%).

PMID- 14567953
TI  - Genetic approaches to stature, pubertal timing, and other complex traits.
AB  - The factors that regulate the timing of puberty remain largely elusive, as do the
      factors that modulate childhood growth and adult height. However, it is clear
      that these developmental processes are highly heritable--much of the natural
      variation in growth and timing of puberty is due to genetic variation within the
      population. In this review, we discuss how recent genetic and genomic advances
      can be exploited to help understand the genetic regulation of these processes. In
      particular, we describe how genome-wide linkage scans and association studies, in
      conjunction with haplotype-based approaches, are potentially useful tools to
      increase our understanding of these two complex traits. Discovery of the genetic
      variants that regulate these two traits would expand our understanding of human
      neuroendocrinology, postnatal development, and the general architecture of
      complex genetic traits.

PMID- 14567954
TI  - The contribution of mitochondria to common disorders.
AB  - Mitochondrial dysfunction secondary to mitochondrial and nuclear DNA mutations
      has been associated with energy deficiency in multiple organ systems and a
      variety of severe, often fatal, clinical syndromes. Although the production of
      energy is indeed the primary function of mitochondria, attention has also been
      directed toward their role producing reactive oxygen and nitrogen species and the
      subsequent widespread deleterious effects of these intermediates. The generation
      of toxic reactive intermediates has been implicated in a number of relatively
      common disorders, including neurodegenerative diseases, diabetes, and cancer.
      Understanding the role mitochondrial dysfunction plays in the pathogenesis of
      common disorders has provided unique insights into a number of diseases and
      offers hope for potential new therapies.

PMID- 14567955
TI  - Control of endocardial cushion and cardiac valve maturation by BMP signaling
      pathways.
AB  - Congenital heart defects, the leading cause of deaths from birth defects, are
      estimated to occur in close to 1% of live newborns. Among these, abnormal
      septation of the heart and valve anomalies are the most frequent forms. Despite
      progress defining several genes involved in normal heart development, we still
      have a limited understanding of the signaling pathways involved in morphogenesis
      of the outflow tract (OFT) and, to date, very few genes have been identified that
      are responsible for defects in humans. Bone Morphogenetic Protein (BMP) signaling
      pathways are emerging as vital regulators of multiple aspects of cardiogenesis,
      including the septation of the OFT and valve maturation. Genetic and other in
      vivo evidence is now supporting the role for BMPs as inducers of endocardial
      cushion epithelial-to-mesenchymal transformation that was suggested by in vitro
      explant studies as well as by their patterns of expression in the developing
      heart. Here, we review briefly the in vitro data, and detail the novel mouse
      models where perturbed BMP signaling pathways result in impaired OFT septation
      and semilunar valvulogenesis. We propose that growth of the OFT valve cushions is
      regulated by the level of BMP signaling, under the control of other signaling
      pathways.

PMID- 14567956
TI  - Human malformations of the midbrain and hindbrain: review and proposed
      classification scheme.
AB  - Although a great deal of interest in the genetics and etiology of cerebral,
      particularly forebrain, malformations has been generated in the past decade,
      relatively little is known about the basis of congenital malformations of the
      structures of the posterior fossa, namely the midbrain, cerebellum, pons, and
      medulla. In this review, we present a classification scheme for malformations of
      the midbrain and hindbrain based on their embryologic derivation, highlight four
      of the conditions associated with such abnormalities, and describe the genetics,
      prognosis, and recurrence risks for each. We describe several disorders in
      addition to Joubert syndrome with the distinctive radiologic sign known as the
      "molar tooth sign," comprised of midbrain and hindbrain malformations. We discuss
      Dandy-Walker malformation, its classical definition, and the surprisingly good
      outcome in the absence of other brain malformations. We consider the
      heterogeneous entity of cerebellar vermis hypoplasia and describe the recently
      identified gene associated with an X-linked form of this condition. Finally, the
      pontocerebellar hypoplasias are discussed in the context of their generally
      progressive degenerative and severe course, and the differential diagnosis is
      emphasized. We anticipate that as imaging technologies improve, differentiation
      of the various disorders should aid in efforts to identify the causative genes.

PMID- 14567957
TI  - Development and malformations of the cerebellum in mice.
AB  - The cerebellum is the primary motor coordination center of the CNS and is also
      involved in cognitive processing and sensory discrimination. Multiple cerebellar
      malformations have been described in humans, however, their developmental and
      genetic etiologies currently remain largely unknown. In contrast, there is
      extensive literature describing cerebellar malformations in the mouse. During the
      past decade, analysis of both spontaneous and gene-targeted neurological mutant
      mice has provided significant insight into the molecular and cellular mechanisms
      that regulate cerebellar development. Cerebellar development occurs in several
      distinct but interconnected steps. These include the establishment of the
      cerebellar territory along anterior-posterior and dorsal-ventral axes of the
      embryo, initial specification of the cerebellar cell types, their subsequent
      proliferation, differentiation and migration, and, finally, the interconnection
      of the cerebellar circuitry. Our understanding of the basis of these
      developmental processes is certain to provide insight into the nature of human
      cerebellar malformations.

PMID- 14567958
TI  - Genetic basis of Hirschsprung disease: implications in clinical practice.

PMID- 14567959
TI  - Canavan disease: a monogenic trait with complex genomic interaction.
AB  - Canavan disease (CD) is an inherited leukodystrophy, caused by aspartoacylase
      (ASPA) deficiency, and accumulation of N-acetylaspartic acid (NAA) in the brain.
      The gene for ASPA has been cloned and more than 40 mutations have been described,
      with two founder mutations among Ashkenazi Jewish patients. Screening of
      Ashkenazi Jews for these two common mutations revealed a high carrier frequency,
      approximately 1/40, so that programs for carrier testing are currently in
      practice. The enzyme deficiency in CD interferes with the normal hydrolysis of
      NAA, which results in disruption of myelin and spongy degeneration of the white
      matter of the brain. The clinical features of the disease are macrocephaly, head
      lag, progressive severe mental retardation, and hypotonia in early life, which
      later changes to spasticity. A knockout mouse for CD has been generated, and used
      to study the pathophysiological basis for CD. Findings from the knockout mouse
      indicate that this monogenic trait leads to a series of genomic interaction in
      the brain. Changes include low levels of glutamate and GABA. Microarray
      expression analysis showed low level of expression of GABA-A receptor (GABRA6)
      and glutamate transporter (EAAT4). The gene Spi2, a gene involved in apoptosis
      and cell death, showed high level of expression. Such complexity of gene
      interaction results in the phenotype, the proteome, with spongy degeneration of
      the brain and neurological impairment of the mouse, similar to the human
      counterpart. Aspartoacylase gene transfer trial in the mouse brain using
      adenoassociated virus (AAV) as a vector are encouraging showing improved
      myelination and decrease in spongy degeneration in the area of the injection and
      also beyond that site.

PMID- 14567960
TI  - DAX1 and its network partners: exploring complexity in development.
AB  - DAX1 encoded by NR0B1, when mutated, is responsible for X-linked adrenal
      hypoplasia congenita (AHC). AHC is due to failure of the adrenal cortex to
      develop normally and is fatal if untreated. When duplicated, this gene is
      associated with an XY sex-reversed phenotype. DAX1 expression is present during
      development of the steroidogenic hypothalamic-pituitary-adrenal-gonadal (HPAG)
      axis and persists into adult life. Despite recognition of the crucial role for
      DAX1, its function remains largely undefined. The phenotypes of patients and
      animal models are complex and not always in agreement. Investigations using cell
      lines have proved difficult to interpret, possibly reflecting cell line choices
      and their limited characterization. We will review the efforts of our group and
      others to identify appropriate cell lines for optimizing ex vivo analysis of
      NR0B1 function throughout development. We will examine the role of DAX1 and its
      network partners in development of the hypothalamic-pituitary-adrenal/gonadal
      axis (HPAG) using a variety of different types of investigations, including those
      in model organisms. This network analysis will help us to understand normal and
      abnormal development of the HPAG. In addition, these studies permit
      identification of candidate genes for human inborn errors of HPAG development.

PMID- 14567961
TI  - RNA interference and human disease.
AB  - The completion of the human genome project has left researchers searching for an
      efficient method to study gene function in mammalian cells. RNA interference
      (RNAi) is an evolutionarily conserved post-transcriptional gene silencing (PTGS)
      mechanism mediated by double-stranded RNA (dsRNA). The dsRNA is processed into
      small duplex RNA molecules of approximately 21-22 nucleotides (nts) termed small
      interfering RNAs (siRNAs) by a RNase III enzyme called Dicer. Interaction of
      siRNAs with a multi-protein complex, termed the RNA-induced silencing complex
      (RISC), results in sequence specific association of the activated RISC complex
      with the cognate RNA transcript. This interaction leads to sequence-specific
      cleavage of the target transcript. Originally discovered in Caenorhabditis
      elegans, the study of RNAi in mammalian cells has blossomed in the last couple of
      years with the discovery that introduction of siRNA molecules directly into
      somatic mammalian cells circumvents the non-specific response vertebrate cells
      have against larger dsRNA molecules. Emerging as a powerful tool for reverse
      genetic analysis, RNAi is rapidly being applied to study the function of many
      genes associated with human disease, in particular those associated with
      oncogenesis and infectious disease. This review summarizes the mechanism of RNAi
      and provides an overview of its current applications in medicine.

PMID- 14567962
TI  - Neonatal hemoglobinopathy screening: molecular genetic technologies.

PMID- 14567963
TI  - Recent progress in the development of assays suited for histone deacetylase
      inhibitor screening.
AB  - Histone deacetylase (HDAC) inhibitors have an unprecedented potential to occupy a
      major position in the future market of anticancer agents. However, progress in
      the development of these new chemotherapeutics is largely dependent on the
      existence of bioassays well-suited for inhibitor screening. Herein, we summarize
      recent developments in HDAC assay technology and, particularly, discuss different
      assay types with respect to their suitability for high-throughput screening
      programs.

PMID- 14567964
TI  - Fatal systemic inflammatory response syndrome in a ornithine transcarbamylase
      deficient patient following adenoviral gene transfer.
AB  - We report the death of an 18-year-old male with partial ornithine
      transcarbamylase (OTC) deficiency who participated in a pilot (safety) study of
      gene therapy. The vector used for this trial was based on human adenovirus type
      5, deleted in E1 and E4, and contained human OTC cDNA. It was infused into the
      right hepatic artery at a dose of 6x10(11)particles/kg. Approximately 18 h.
      following gene transfer the subject was noted to have altered mental status and
      jaundice--clinical signs not seen in any of the first 17 subjects in this study.
      Subsequently, his clinical course was marked by systemic inflammatory response
      syndrome, biochemically detectable disseminated intravascular coagulation, and
      multiple organ system failure, leading to death 98 h following gene transfer.
      Post-mortem examination was consistent with the clinical course, and vector DNA
      sequences were readily detectable in most tissues. The subject had high serum
      levels of IL-6 and IL-10 but normal TNFalpha immediately after infusion of the
      vector. This experience points to the limitations of animal studies in predicting
      human responses, the steep toxicity curve for replication defective adenovirus
      vectors, substantial subject-to-subject variation in host responses to
      systemically administered vectors, and the need for further study of the immune
      response to these vectors.

PMID- 14567965
TI  - Enzyme replacement therapy in the mouse model of Pompe disease.
AB  - Deficiency of acid alpha-glucosidase (GAA) results in widespread cellular
      deposition of lysosomal glycogen manifesting as myopathy and cardiomyopathy. When
      GAA-/- mice were treated with rhGAA (20 mg/kg/week for up to 5 months), skeletal
      muscle cells took up little enzyme compared to liver and heart. Glycogen
      reduction was less than 50%, and some fibers showed little or no glycogen
      clearance. A dose of 100 mg/kg/week resulted in approximately 75% glycogen
      clearance in skeletal muscle. The enzyme reduced cardiac glycogen to undetectable
      levels at either dose. Skeletal muscle fibers with residual glycogen showed
      immunoreactivity for LAMP-1/LAMP-2, indicating that undigested glycogen remained
      in proliferating lysosomes. Glycogen clearance was more pronounced in type 1
      fibers, and histochemical analysis suggested an increased mannose-6-phosphate
      receptor immunoreactivity in these fibers. Differential transport of enzyme into
      lysosomes may explain the strikingly uneven pattern of glycogen removal.
      Autophagic vacuoles, a feature of both the mouse model and the human disease,
      persisted despite glycogen clearance. In some groups a modest glycogen reduction
      was accompanied by improved muscle strength. These studies suggest that enzyme
      replacement therapy, although at much higher doses than in other lysosomal
      diseases, has the potential to reverse cardiac pathology and to reduce the
      glycogen level in skeletal muscle.

PMID- 14567966
TI  - Targeting proteins to mitochondria using TAT.
AB  - Disorders of mitochondrial function cause significant human disease and
      suffering. To date, correction of these mitochondria defects has depended on
      biochemical approaches and has not been achieved via gene therapies. Using
      previously described fusion proteins containing the transactivator of
      transcription (TAT) region from the HIV virus and green fluorescent protein
      (GFP), with and without a mitochondrial targeting sequence (MTS) from
      mitochondrial malate dehydrogenase (mMDH), we have investigated transduction
      across mitochondrial membranes. Both TAT-GFP and TAT-mMDH-GFP fusion proteins are
      protected from externally added protease when incubated with isolated
      mitochondria. Furthermore, both TAT fusion proteins rapidly enter cultured cells
      and transduce into mitochondria. However, the MTS allows processing of the fusion
      protein and is necessary for persistence in mitochondria over time. Neither
      degradation of import receptors nor disruption of the mitochondrial membrane
      potential or pH gradient inhibits protein transduction of either fusion protein.
      Furthermore, when injected into pregnant mice, TAT-mMDH-GFP is detectable
      throughout fetal and neonatal pups. These results indicate that TAT fusion
      proteins are able to traverse mitochondrial membranes through mechanisms that do
      not involve the regular import pathway, and that the addition of a MTS allows
      persistence of the fusion protein within mitochondria. TAT-MTS fusion proteins
      may represent a viable option as potential mitochondrial protein therapies.

PMID- 14567968
TI  - Relationship of causative genetic mutations in maple syrup urine disease with
      their clinical expression.
AB  - Maple syrup urine disease [MSUD] is a rare inborn error of metabolism inherited
      as an autosomal recessive trait through mutations in any of three different genes
      that encode components of the branched chain alpha-ketoacid dehydrogenase [BCKD]
      complex. In this work, the genotype of affected individuals was correlated with
      their clinical histories. These individuals were diagnosed and followed in a
      single centralized clinic, and their molecular genetic characterization was done
      by one laboratory. Three individuals had mutant alleles in the gene for the
      E1alpha component, five had mutations in the gene for E1beta, and three had
      mutations in the gene for E2. The results emphasize the diversity of the
      molecular and clinical presentations for individuals with MSUD and support the
      complexity of diseases termed "single gene traits." Of primary importance is
      early identification of at risk infants through newborn screening programs to
      minimize many of the complications associated with this protein intolerance.
      Attention to abnormal neurological signs in the neonate or evidence of
      neurological decompensation in older infants and children by a centralized
      medical management team minimizes permanent brain damage and improves survival.

PMID- 14567967
TI  - Improved growth and nutrition status in children with methylmalonic or propionic
      acidemia fed an elemental medical food.
AB  - BACKGROUND: Failure-to-thrive (FTT) has been described in patients with organic
      acidemias treated with low protein diets. OBJECTIVE: To determine if patients
      with methylmalonic (MMA) or propionic acidemia (PA) can achieve normal growth and
      nutrition status. METHODS: A 6-month multicenter outpatient study was conducted
      with infants and toddlers treated with Propimex-1 Amino Acid-Modified Medical
      Food With Iron (Ross Products Division, Abbott Laboratories, Columbus, OH). Main
      outcome measures were anthropometrics, protein status indices, plasma retinol,
      and alpha-tocopherol. RESULTS: Sixteen patients completed the study. Mean
      baseline age was 0.54 +/- 0.02 years (range 0.03-3.00 years). By study end, mean
      National Center for Health Statistics (NCHS) weight centile increased from 26 to
      49%; mean crown-heel length centile from 25 to 33%; and mean head circumference
      centile from 43 to 54%. Mean (+/- SE) protein and energy intakes by <6-month-old,
      6<12-month-old, and 1<4-year-old patients were 15.3 +/- 0.9 g and 645 +/- 10
      kcal; 18.3 +/- 1.1 g and 741 +/- 92 kcal; and 25.1 +/- 2.46 g and 1062 +/- 100
      kcal, respectively. Plasma glycine concentrations were significantly and
      negatively correlated with energy intake (r=-0.77, p<0.0005). No correlation was
      found between dietary protein intakes and plasma ammonia concentrations. Protein
      status indices, retinol and alpha-tocopherol concentrations were within reference
      ranges at study end. CONCLUSIONS: Propimex-1 improved growth and nutrition status
      in patients with MMA or PA in just 6 months when fed in sufficient amounts.
      Providing energy and protein for patients with FTT at intakes recommended for
      catch-up growth may have resulted in even better growth.

PMID- 14567969
TI  - Genotypic determinants of phenotype in North American patients with
      erythropoietic protoporphyria.
AB  - Erythropoietic protoporphyria (EPP) is characterized by excess accumulation of
      protoporphyrin, which is due to deficient activity of the enzyme ferrochelatase
      (FECH). This results in photosensitivity and in some patients liver disease which
      may necessitate liver transplantation. The aim of this study was to delineate the
      abnormalities in the FECH gene which cause phenotypic expression in EPP. We
      identified 43 individuals from 25 North American families with EPP who were
      heterozygous for various FECH mutations, but the mutations did not adequately
      explain the variable phenotype. We also examined the presence of an intron
      polymorphism (IVS3-48c) in the FECH gene which was shown to cause the formation
      of aberrantly spliced FECH mRNA. FECH DNA analysis demonstrated that 94% of 31
      symptomatic individuals with FECH mutations were heterozygous for IVS3-48c,
      whereas 12 asymptomatic individuals with FECH mutations were homozygous for IVS3
      48t. Haplotype analysis in four families showed that symptomatic members had the
      IVS3-48c polymorphism in the non-mutant FECH allele. Sequencing of the proximal
      FECH gene promoter showed no additional changes which might affect gene
      expression. The levels of normal FECH mRNA, measured by relative quantitative RT
      PCR, and FECH enzyme activity were correspondingly lower in the cultured
      lymphoblasts of family members with the IVS3-48c polymorphism. These results
      indicate that symptomatic disease in most North American patients with EPP is
      explained by the inheritance of a mutation in one FECH allele which causes a
      structural alteration in the protein, together with a low expressing non-mutant
      FECH allele which is caused by the IVS3-48c polymorphism.

PMID- 14567971
TI  - Alternative splicing within the ligand binding domain of the human constitutive
      androstane receptor.
AB  - The human constitutive androstane receptor (hCAR; NR1I3) is a member of the
      nuclear receptor superfamily. The activity of hCAR is regulated by a variety of
      xenobiotics including clotrimazole and acetaminophen metabolites. hCAR, in turn,
      regulates a number of genes responsible for xenobiotic metabolism and transport
      including several cytochrome P450s (CYP 2B5, 2C9, and 3A4) and the multidrug
      resistance-associated protein 2 (MRP2, ABCC2). Thus, hCAR is believed to be a
      mediator of drug-drug interactions. We identified two novel hCAR splice variants:
      hCAR2 encodes a receptor in which alternative splice acceptor sites are utilized
      resulting in a 4 amino acid insert between exons 6 and 7, and a 5 amino acid
      insert between 7 and 8, and hCAR3 encodes a receptor with exon 7 completely
      deleted resulting in a 39 amino acid deletion. Both hCAR2 and hCAR3 mRNAs are
      expressed in a pattern similar to the initially described MB67 (hCAR1) with some
      key distinctions. Although the levels of expression vary depending on the tissue
      examined, hCAR2 and hCAR3 contribute 6-8% of total hCAR mRNA in liver. Analysis
      of the activity of these variants indicates that both hCAR2 and hCAR3 lose the
      ability to heterodimerize with RXR and lack transactivation activity in
      cotransfection experiments where either full-length receptor or GAL4 DNA-binding
      domain/CAR ligand binding domain chimeras were utilized. Although the role of
      hCAR2 and hCAR3 is currently unclear, these additional splice variants may
      provide for increased diversity in terms of responsiveness to xenobiotics.

PMID- 14567970
TI  - Mutations in the muscle LIM protein and alpha-actinin-2 genes in dilated
      cardiomyopathy and endocardial fibroelastosis.
AB  - Dilated cardiomyopathy (DCM) is a major cause of morbidity and mortality. Two
      genes have been identified for the X-linked forms (dystrophin and tafazzin),
      while mutations in multiple genes cause autosomal dominant DCM. Muscle LIM
      protein (MLP) is a member of the cysteine-rich protein (CRP) family and has been
      implicated in both myogenesis and sarcomere assembly. In the latter role, it
      binds zyxin and alpha-actinin, both of which are involved in actin organization.
      An MLP-deficient mouse has been described; these mice develop dilated
      cardiomyopathy and heart failure. Based upon these data, and the recent
      descriptions of mutations in MLP in patients with DCM or hypertrophic
      cardiomyopathy, we screened patients for mutations in the MLP and alpha-actinin-2
      genes. We identified a patient with DCM and EFE, having a mutation in MLP with
      the residue lysine 69 substituted by arginine (K69R). This is within a highly
      conserved region adjacent to the first LIM domain involved in alpha-actinin
      binding. Analysis in cell culture systems demonstrated that the mutation
      abolishes the interaction between MLP and alpha-actinin-2 and the cellular
      localization of MLP was altered. In another individual with DCM, a W4R mutation
      was identified. However, this mutation did not segregate with disease in this
      family. In another patient with DCM, a Q9R mutation was identified in alpha
      actinin-2. This mutation also disrupted the interaction with MLP and appeared to
      inhibit alpha-actinin function in cultured cells, in respect to the nuclear
      localization of actinin and the initiation of cellular differentiation.

PMID- 14567972
TI  - Identification of two novel mutations in the murine Nsdhl sterol dehydrogenase
      gene and development of a functional complementation assay in yeast.
AB  - Nsdhl is a 3beta-hydroxysterol dehydrogenase that is involved in the removal of C
      4 methyl groups in the cholesterol biosynthetic pathway. Mutations in this gene
      are associated with the X-linked male lethal mouse mutations bare patches (Bpa)
      and striated (Str) and human CHILD syndrome. We have now detected the missense
      mutations V53D and A94T in conserved amino acids in two additional Bpa alleles.
      The latter alters the same amino acid as a missense mutation found in two
      unrelated CHILD patients, strongly suggesting that differences in the phenotype
      between Bpa mice and females with CHILD syndrome are unlikely to be explained by
      different types or sites of mutations. We have also demonstrated that the mouse
      NSDHL protein can rescue the lethality of erg26 deficient cells of Saccharomyces
      cerevisiae that lack the yeast ortholog, substantiating the role of NSDHL as a C
      3 sterol dehydrogenase. Using this in vivo assay, we have demonstrated that two
      Str alleles function as hypomorphs, while three Bpa and one Str allele provide no
      complementation or rescue.

PMID- 14567973
TI  - Male infertility and thiamine-dependent erythroid hypoplasia in mice lacking
      thiamine transporter Slc19a2.
AB  - Thiamine-responsive megaloblastic anemia with diabetes and deafness (TRMA) is an
      autosomal recessive disease caused by mutations in the high-affinity thiamine
      transporter gene SLC19A2. To study the role of thiamine transport in the
      pathophysiology of TRMA syndrome and of each of the component disorders, we
      created a targeted disruption of the Slc19a2 gene in mice. Slc19a2 -/- mice are
      viable and females are fertile. Male -/- mice on a pure 129/Sv background are
      infertile with small testes (testis/body weight=0.13 +/- 0.04 knockout vs. 0.35
      +/- 0.05 wild type, P<0.000005). The lack of developing germ cells beyond primary
      spermatocytes suggests an arrest in spermatogenesis prior to meiosis II. Nuclear
      chromatin changes indicative of apoptosis are present. No mature sperm are found
      in the tubules or epididymis. This phenotype suggests a previously unknown role
      for thiamine transport in spermatogenesis and male fertility. Slc19a2 -/- mice on
      a pure 129/Sv background develop reticulocytopenia after two weeks on thiamine
      depleted chow with a virtual absence of reticulocytes in the peripheral blood
      (0.12% knockout vs. 2.58% wild type, P=0.0079). Few erythroid precursors are
      found in the bone marrow. Contrary to human TRMA syndrome, we see no evidence of
      megaloblastosis or ringed sideroblasts in the bone marrow of Slc19a2 -/- mice in
      thiamine-replete or thiamine-deficient dietary states. Phenotypic differences
      between TRMA patients and Slc19a2 -/- mice might be explained by dissimilar
      tissue expression patterns of the transporter, as well as by differing metabolic
      needs and possible different species-specific contributions of the related
      thiamine transporter Slc19a3.

PMID- 14567974
TI  - Thyroid hormone affects distal airway formation during the late pseudoglandular
      period of mouse lung development.
AB  - We recently showed that T3 treatment of cultured gestational day 11.5 early
      pseudoglandular period mouse lungs, accelerated terminal airway development at
      the expense of decreased branching morphogenesis. As the ability of T3 to
      influence epithelial cell differentiation increases with advancing development,
      we hypothesized that in the late pseudoglandular period, T3 would cause further
      premature changes in the morphology of the distal airways leading to abnormal
      saccular development. Gestational day 13.5 embryonic mouse lungs were cultured
      for 3 and 7 days without or with added T3. Increasing T3 dose and time in culture
      resulted in progressive development of thin walled, abnormal saccules, an
      increase in cuboidal and flattened epithelia and airway space with a concomitant
      decrease in mesenchymal cell volume. Consistent with increased cuboidal and
      flattened epithelial cell volume identified by morphometry, immunostaining
      suggested increased cell proliferation detected by localization of proliferating
      cell nuclear antigen (PCNA) in epithelial cells of T3 treated lungs. T3 decreased
      mesenchymal expression of Hoxb-5 protein and caused progressive localization of
      Nkx2.1 and SP-C proteins to distal cuboidal epithelia of early abnormal saccules,
      evidence that T3 prematurely and abnormally advanced mesenchymal and epithelial
      cell differentiation. Western blot showed a T3-dependent decrease in Hoxb-5 and a
      trend towards decreased Nkx2.1 and SP-C, after 3 and 7 days of culture,
      respectively. We conclude that exogenous T3 treatment during the late
      pseudoglandular period prematurely and abnormally accelerates terminal saccular
      development. This may lead to abnormal mesenchymal and epithelial cell fate.

PMID- 14567975
TI  - PCR-select subtraction for characterization of messages differentially expressed
      in brown compared with white adipose tissue.
AB  - To understand the energy metabolism occurring in brown adipose tissue (BAT), we
      subtracted the messages expressed in white adipose tissue (WAT) from those in
      BAT. Thereby we succeeded in identifying 37 cDNA clones as being significantly
      expressed in BAT but not in WAT. Of these, 24 clones were found to code for
      mitochondrial proteins. Since BAT is well known to have a higher mitochondrial
      content than WAT, these results would seem to reflect simply the differences in
      mitochondrial content between BAT and WAT. To examine this possibility, we next
      measured the amount of mitochondrial DNA (mtDNA) in various rat tissues. As a
      result, the mtDNA copy number per cell was found to be markedly different among
      the tissues analyzed, and the highest value of about 5.3x10(4) copies per cell
      was observed with the rat brain. BAT showed a value similar to that of brain, but
      this value was only about 3.5-fold higher than that for WAT. Since observed
      differences in mitochondrial content between BAT and WAT was smaller than those
      observed with transcript levels of proteins, we conclude that the observed
      differences in the transcript levels of certain proteins between BAT and WAT
      reflect the functional differences between BAT and WAT, and do not reflect the
      differences in mitochondrial content between BAT and WAT.

PMID- 14567976
TI  - Differential gene expression in skeletal muscle after induction of heart failure:
      impact of cytokines on protein phosphatase 2A expression.
AB  - Different intrinsic alterations of skeletal muscle metabolism and gene expression
      have been described in chronic heart failure (CHF). As proposed skeletal muscle
      alterations in CHF may contribute to exercise intolerance and early muscular
      fatigue. However the exact molecular changes occurring in the skeletal muscle are
      still unclear. The aim of this study was to characterize the pattern of
      differential gene expression in an animal model of CHF and to study the
      regulation of one selected gene. Rats were subjected to LAD ligation or sham
      operation. mRNA was isolated from musculus quadriceps of both groups and
      differential gene expression was determined by subtractive hybridization.
      Quantitative RT-PCR and cell culture experiments were performed to further
      characterize the changed expression of protein phosphatase 2A (PP2A) in human
      skeletal muscle biopsies as well as the cytokine dependent regulation of PP2A
      expression. Out of 800 picked clones differential expression of 24 distinct genes
      could be identified by sequencing and reverse Northern blotting. PP2A expression
      demonstrated a significant upregulation in skeletal muscle biopsies from patients
      with CHF as compared to healthy controls (9.7 +/- 1.9 vs. 4.2 +/- 0.7 arbitrary
      units; p<0.05). Incubation of rat skeletal muscle myoblasts with a combination of
      TNF-alpha, IL-1beta, and gamma-IFN caused a 3-fold upregulation of PP2A
      expression vs. untreated cells. These results suggest that CHF is accompanied by
      changes in expression of genes involved in energy metabolism, contractility, and
      apoptosis in the skeletal muscle. The upregulation of PP2A, an important
      regulator in intracellular signaling and apoptosis, may be due to an increase of
      inflammatory cytokines.

PMID- 14567977
TI  - N-myc oncogene expression in neuroblastoma is driven by Sp1 and Sp3.
AB  - Regulation of N-myc oncogene expression is an important determinant of the
      biological behavior of neuroblastoma. The N-myc promoter contains several
      potential binding sites for transcription factors of the Sp1 family. Mutation of
      a CT-box motif contained within a 26 bp region required for N-myc downregulation
      by retinoic acid decreased basal transcriptional activity and altered DNA-protein
      interactions of the promoter, while mutations flanking this motif did neither. On
      super-shift, this region was shown to recruit Sp1 and Sp3 transcription factor
      proteins, while a functionally significant CT-box mutation resulted in their
      replacement by NF-1 transcription factor. Lysates from Drosophila S2 cells
      expressing exogenous Sp1, Sp3, and NF-1 proteins were able to partially mimic gel
      shift complexes seen with neuroblastoma nuclear extract and either wild type or
      mutant probes. Transient transfections of S2 cells showed that both individually
      and together, Sp1 and Sp3 were able to trans-activate a wild type CT-box-driven
      luciferase reporter construct in a dose-dependent manner. Transfection of the
      wild type but not mutant CT-box oligonucleotide was able to decrease endogenous N
      myc expression in neuroblastoma cells. Together these results suggest that the CT
      box element serves a critically functional role, and in the basal state, allows
      for N-myc trans-activation by Sp1 and Sp3. Moreover when mutated, the CT-box may
      still function as a binding motif for alternate transcription factors such as NF
      1 that can allow persistent N-myc expression.

PMID- 14567978
TI  - The rise of DNA methylation and the importance of chromatin on multidrug
      resistance in cancer.
AB  - In recent years, the different classes of drugs and regimens used clinically have
      provided an improvement in tumour management. However, treatment is often
      palliative for the majority of cancer patients. Transformed cells respond poorly
      to chemotherapy mainly due to the development of the multidrug resistance (MDR)
      phenotype. Response to treatment does not generally result in complete remission
      and disease cure is uncommon for patients presenting with advanced stage cancer.
      Successful treatment of cancer requires a clearer understanding of
      chemotherapeutic resistance. Here, we examine what is known of one of the most
      extensively studied mechanisms of cellular drug resistance. The human multidrug
      resistance gene 1 (MDR1) is associated with expression of p-glycoprotein (Pgp). A
      transmembrane protein, Pgp acts as an efflux pump and reduces intracellular drug
      levels and thus its effectiveness as an antitumor agent. The precise mechanism of
      transcriptional regulation has been unclear due to the complex regulatory nature
      of the gene. It has become increasingly apparent that trans-activation or genetic
      amplification is by no means the only mechanism of activation. Consequently,
      alternative pathways have received more attention in the area of epigenetics to
      help explain transcriptional competence at a higher level of organization. The
      goal of this article is to highlight important findings in the field of
      methylation and explain how they impinge on MDR1 gene regulation. In this review,
      we cover the current information and postulate that epigenetic modification of
      MDR1 chromatin influences gene transcription in leukaemia. Finally, we explore
      transcriptional regulation and highlight recent progress with engineered ZFP's
      (zinc finger proteins).

PMID- 14567979
TI  - Metabolic stabilization of MAP kinase phosphatase-2 in senescence of human
      fibroblasts.
AB  - Cellular senescence is characterized by impaired cell proliferation. We have
      previously shown that, relative to the young counterpart, senescent WI-38 human
      fibroblasts display a decreased abundance of active phosphorylated ERK (p-ERK) in
      the nucleus. We have tested the hypothesis that this is due to elevated levels of
      nuclear MAP kinase phosphatase (MKP) activity in senescent cells. Our results
      indicate that the activity and abundance of MKP-2 is increased in senescent
      fibroblasts, compared to their young counterparts. Further analysis indicates
      that it is MKP-2 protein, but not MKP-2 mRNA level, that is increased in
      senescent cells. This increase is the result of the increased stability of MKP-2
      protein against proteolytic degradation. The degradation of MKPs was impaired by
      proteasome inhibitors both in young and old WI-38 cells, indicating that
      proteasome activity is involved in the degradation of MKPs. Finally, our results
      indicate that proteasome activity, in general, is diminished in senescent
      fibroblasts. Taken together, these data indicate that the increased level and
      activity of MKP-2 in senescent WI-38 cells are the consequence of impaired
      proteosomal degradation, and this increase is likely to play a significant role
      in the decreased levels of p-ERK in the nucleus of senescent cells.

PMID- 14567980
TI  - Skeletal myogenic progenitors in the endothelium of lung and yolk sac.
AB  - We previously showed that clonable skeletal myogenic cells can be derived from
      the embryonic aorta but become very rare in the more mature and structured fetal
      aorta. The aim of this study was to investigate whether, during fetal and
      postnatal development, these myogenic progenitors progressively disappear or may
      rather associate with the microvascular district, being thus distributed to
      virtually all tissues. To test this hypothesis, we used F1 embryos (or mice) from
      a transgenic line expressing a striated muscle-specific reporter gene (LacZ)
      crossed with a transgenic line expressing a different endothelial-specific
      reporter genes (GFP). Endothelial cells were isolated from yolk sac (at E11) and
      lung (at E11, E17, P1, P10, and P60), two organs embryologically unrelated to
      paraxial mesoderm, rich in vessels, and devoid of skeletal muscle. Endothelial
      cells, purified by magnetic bead selection (CD31/PECAM-1(+)) or cell sorting
      (Tie2-GFP(+)) were then challenged for their skeletal myogenic potential in vitro
      and in vivo. The results demonstrated that both yolk sac and lung contain
      progenitor cells, which express endothelial markers and are endowed with a
      skeletal myogenic potential that they reveal when in the presence of
      differentiating myoblasts, in vitro, and regenerating muscle, in vivo. The number
      (or potency to generate skeletal muscle) of these vessels associated cells
      decreases rapidly with age and is very low in mature animals, possibly
      correlating with reduced regenerative capacity of adult mammalian tissues.

PMID- 14567981
TI  - Morphological evidence of the importance of epithelial tissue during mouse tongue
      development.
AB  - The morphogenesis of fungiform papillae occurs in a stereotyped pattern on the
      dorsal surface of the tongue in mice from embryonic day 12 (E12) to E17. The
      histological results and ultrastructural observations showed the development of
      specific structures in the epithelium into fungiform papillae. Prior to the
      morphological changes, the Bmp-4 and Shh transcripts are expressed in a
      restricted area on the dorsal surface. These results suggest that the development
      of fungiform papillae requires an epithelium and mesenchyme interaction during
      morphogenesis. In order to obtain direct evidence of the epithelium and
      mesenchyme interaction during tongue papillae morphogenesis, the formation of
      fungiform papillae was examined after a recombination assay. In order to confirm
      the epithelium and mesenchyme interactions during the early development of the
      mouse tongue, a recombination assay was conducted after the recombination assay
      at E12.5 and E13.5 for 2 days using an in vitro organ culture. From the
      recombination assay results, the E13.5 epithelial portion of the fungiform
      papillae could determine the position of the newly formed fungiform papillae with
      the epithelial signaling molecules. E13.5 was a critical stage for fungiform
      papillae morphogenesis. Fungiform papillae can be considered to be small
      epithelial appendages, which are formed via the epithelium and mesenchyme
      interactions.

PMID- 14567982
TI  - Disruption of microtubules inhibits cytoplasmic ribonucleoprotein stress granule
      formation.
AB  - Stress granules are RNP-containing particles arising in the cytoplasm in response
      to environmental stress. They are dynamic structures assembling and disassembling
      in the cytoplasm very rapidly. We have studied whether the cytoskeleton is
      involved in the formation of stress granules. Stress granules were induced in CV
      1 cells by sodium arsenate treatment and visualized by immunofluorescent staining
      with antibodies either to the p170 subunit of eIF3 or to poly(A)-binding protein.
      Treatment with sodium arsenate for 30-120 min led to assembling of stress
      granules in a majority of CV-1 cells. Disruption of MT array with nocodazole
      treatment abolished arsenate-induced formation of stress granules. A similar
      effect was induced by the microtubule-depolymerizing drug vinblastine, though the
      influence of the microtubule-stabilizing drug paclitaxel was opposite. Nocodazole
      treatment did not prevent arsenate-induced phosphorylation of the eIF-2alpha
      factor, essential for stress granule formation, suggesting that the presence of
      intact MT array is required for granule assembly. Unexpectedly, treatment of
      cells with the actin filament-disrupting drug latrunculin B slightly enhanced
      stress granule formation. We propose that stress granule formation is microtubule
      dependent process and likely is facilitated by the motor protein-driven movement
      of individual stress granule components (e.g., mRNP) along microtubules.

PMID- 14567983
TI  - Transcription factor Nrf2 activation by inorganic arsenic in cultured
      keratinocytes: involvement of hydrogen peroxide.
AB  - Inorganic arsenic is a well-documented human carcinogen that targets the skin.
      The induction of oxidative stress, as shown with arsenic, may have a bearing on
      the carcinogenic mechanism of this metalloid. The transcription factor Nrf2 is a
      key player in the regulation of genes encoding for many antioxidative response
      enzymes. Thus, the effect of inorganic arsenic (as sodium arsenite) on Nrf2
      expression and localization was studied in HaCaT cells, an immortalized human
      keratinocyte cell line. We found, for the first time, that arsenic enhanced
      cellular expression of Nrf2 at the transcriptional and protein levels and
      activated expression of Nrf2-related genes in these cells. In addition, arsenic
      exposure caused nuclear accumulation of Nrf2 in association with downstream
      activation of Nrf2-mediated oxidative response genes. Arsenic simultaneously
      increased the expression of Keap1, a regulator of Nrf2 activity. The coordinated
      induction of Keap1 expression and nuclear Nrf2 accumulation induced by arsenic
      suggests that Keap1 is important to arsenic-induced Nrf2 activation. Furthermore,
      when cells were pretreated with scavengers of hydrogen peroxide (H(2)O(2)) such
      as catalase-polyethylene glycol (PEG-CAT) or Tiron, arsenic-induced nuclear Nrf2
      accumulation was suppressed, whereas CuDIPSH, a cell-permeable superoxide
      dismutase (SOD) mimic compound that produces H(2)O(2) from superoxide (*O(2)(-)),
      enhanced Nrf2 nuclear accumulation. These results indicate that H(2)O(2), rather
      than *O(2)(-), is the mediator of nuclear Nrf2 accumulation. Additional study
      showed that arsenic causes increased cellular H(2)O(2) production and that
      H(2)O(2) itself has the ability to increase Nrf2 expression at both the
      transcription and protein levels in HaCaT cells. Taken together, these data
      clearly show that arsenic increases Nrf2 expression and activity at multiple
      levels and that H(2)O(2) is one of the mediators of this process.

PMID- 14567984
TI  - Adhesion dynamics and cytoskeletal structure of gliding human fibrosarcoma cells:
      a hypothetical model of cell migration.
AB  - During motility of fibroblast type cells on planar surfaces, adhesions are formed
      at the anterior of the protruding lamella, which remain stationary relative to
      the substrate and undergo a maturation process as the cell passes over them.
      Through these adhesions force is exerted, the orientation of which is parallel to
      the direction of the movement. Here we show that, during gliding-type motility of
      human tumor cells, characterized by a semicircular shape, adhesions were found at
      the outer rim of the cells, along the semicircle. Time-lapse microscopy of GFP
      vinculin-expressing cells showed that these adhesions were constantly renewed at
      the cell edge and followed a curved trajectory according to the graded radial
      extension model. Eventually, the adhesions reached the long axis of the cell
      where they were retracted into the cell body. Actin cables formed arcs, with the
      concave face at the anterior of the lamella found to be oriented in the direction
      of movement. Since adhesions moved backward with respect to the cell, actin
      cables connected to these adhesions must continuously grow, reaching maximal size
      at the long axis of the cell. Contraction of the arcs is responsible for the
      forward movement of the cell body.

PMID- 14567985
TI  - The importance to chondrocyte differentiation of changes in expression of the
      multiple inositol polyphosphate phosphatase.
AB  - It is important to both physiological and pathological osteogenesis to understand
      the significance of changes in gene expression in growth-plate chondrocytes that
      transit between the proliferative and hypertrophic states. MINPP is one such gene
      of interest. The Minpp protein dephosphorylates highly phosphorylated inositol
      signaling molecules InsP(5) and InsP(6). We show here that the ATDC5 chondrocyte
      progenitor cell line can recapitulate developmentally specific changes in MINPP
      expression previously only seen in longitudinal bone growth plates-both an
      initial 2-3-fold increase and a subsequent decrease back to initial levels during
      transition to hypertrophy. The increase in MINPP expression was accompanied by a
      40% decrease in InsP(6) levels in ATDC5 cells. However, InsP(5) levels were not
      modified. Furthermore, throughout the hypertrophic phase, during which MINPP
      expression decreased, there were no alterations in InsP(5) and InsP(6) levels. We
      also created an ATDC5 line that stably overexpressed Minpp at 2-fold higher
      levels than in wild-type cells. This had no significant effect upon cellular
      levels of InsP(5) and InsP(6). Thus, substantial changes in MINPP expression can
      occur without a net effect upon InsP(5) and InsP(6) turnover in vivo. On the
      other hand, Minpp-overexpressing cells showed impaired chondrogenesis. We noted
      that the expression of alkaline phosphatase activity was inversely correlated
      with the expression of MINPP. The ATDC5 cells that overexpress Minpp failed to
      show an insulin-dependent increase in alkaline phosphatase levels, which
      presumably affects phosphate balance [J. Biol. Chem. 276 (2001) 33995], and may
      be the reason cellular differentiation was impaired. In any case, we conclude
      that Minpp is important to chondrocyte differentiation, but in a manner that is,
      surprisingly, independent of inositol polyphosphate turnover.

PMID- 14567986
TI  - Redistribution of the discs large tumor suppressor protein during mitosis.
AB  - Drosophila discs large (Dlg) has been shown to be an essential regulator of cell
      polarity and attachment, and is classified as a potential tumour suppressor in
      higher eukaryotes. Human Dlg is expressed in epithelial cells at sites of cell
      cell contact and acts as a negative regulator of cell growth. Although hDlg has
      been shown to be phosphorylated during mitosis, little is known about its
      activity during this stage of the cell cycle. To investigate this further we have
      analysed in detail the pattern of hDlg expression during mitotic cell division.
      In early mitosis there is a marked increase in membrane-bound hDlg which is then
      retained throughout mitosis, while during cytokinesis, there is a specific
      concentration of hDlg at the midbody. Using mutants of Dlg we show that this is
      mediated by sequences in the carboxy terminal region of Dlg, but it does not
      require the SH3 or PDZ domains, and is independent of binding to protein 4.1.
      Finally, using a mutant of Dlg that consists of just this carboxy terminal region
      of the protein, we show that it can compete with endogenous hDlg for midbody
      accumulation, and this mutant also gives rise to altered cell growth. We conclude
      that localisation of Dlg to the midbody indicates a role for Dlg at this critical
      point in cytokinesis.

PMID- 14567987
TI  - Cyclic AMP induces phosphorylation of claudin-5 immunoprecipitates and expression
      of claudin-5 gene in blood-brain-barrier endothelial cells via protein kinase A
      dependent and -independent pathways.
AB  - Cyclic AMP (cAMP) promotes functions of tight junctions in endothelial cells,
      although its target remains unknown. We showed here that cAMP increased gene
      expression of claudin-5 and decreased that of claudin-1 in porcine blood-brain
      barrier endothelial cells via protein kinase A (PKA)-independent and -dependent
      pathways, respectively. cAMP also enhanced immunoreactivity of claudin-5 along
      cell borders and in the cytoplasm, reorganized actin filaments, and altered
      signals of claudin-5, occludin, ZO-1, and ZO-2 along cell boundaries from
      zipperlike to linear patterns. In contrast, claudin-1 was detected only in the
      cytoplasm in a dotlike pattern, and its immunolabeling was reduced by cAMP.
      Interestingly, 31- and 62-kDa claudin-5 immunoprecipitates in the NP-40-soluble
      and -insoluble fractions, respectively, were highly phosphorylated on threonine
      residue(s) upon cAMP treatment. All these changes induced by cAMP, except for
      claudin-5 expression and its signals in the cytoplasm, were reversed by an
      inhibitor of PKA, H-89. We also demonstrated that cAMP elevated the barrier
      function of tight junctions in porcine blood-brain-barrier endothelial cells in
      PKA-dependent and -independent manners. These findings indicate that both PKA
      induced phosphorylation of claudin-5 immunoprecipitates and cAMP-dependent but
      PKA-independent induction of claudin-5 expression could be involved in promotion
      of tight-junction function in endothelial cells.

PMID- 14567988
TI  - Possible role of stromal-cell-derived factor-1/CXCR4 signaling on lymph node
      metastasis of oral squamous cell carcinoma.
AB  - We examined the role of chemokine signaling on the lymph node metastasis of oral
      squamous cell carcinoma (SCC) using lymph node metastatic (HNt and B88) and
      nonmetastatic oral SCC cells. Of 13 kinds of chemokine receptors examined, only
      CXCR4 expression was up-regulated in HNt and B88 cells. CXCR4 ligand, stromal
      cell-derived factor-1alpha (SDF-1alpha; CXCL12), induced characteristic calcium
      fluxes and chemotaxis only in CXCR4-expressing cells. CXCR4 expression in
      metastatic cancer tissue was significantly higher than that in nonmetastatic
      cancer tissue or normal gingiva. Although SDF-1alpha was undetectable in either
      oral SCC or normal epithelial cells, submandibular lymph nodes expressed the SDF
      1alpha protein, mainly in the stromal cells, but occasionally in metastatic
      cancer cells. The conditioned medium from lymphatic stromal cells promoted the
      chemotaxis of B88 cells, which was blocked by the CXCR4 neutralization. SDF
      1alpha rapidly activated extracellular signal-regulated kinase (ERK)1/2 and
      Akt/protein kinase B (PKB), and their synthetic inhibitors attenuated the
      chemotaxis by SDF-1alpha. SDF-1alpha also activated Src family kinases (SFKs),
      and its inhibitor PP1 diminished the SDF-1alpha-induced chemotaxis and activation
      of both ERK1/2 and Akt/PKB. These results indicate that SDF-1/CXCR4 signaling may
      be involved in the establishment of lymph node metastasis in oral SCC via
      activation of both ERK1/2 and Akt/PKB induced by SFKs.

PMID- 14567989
TI  - Subunits of the chaperonin CCT are associated with Tetrahymena microtubule
      structures and are involved in cilia biogenesis.
AB  - The cytosolic chaperonin CCT is a heterooligomeric complex of about 900 kDa that
      mediates the folding of cytoskeletal proteins. We observed by indirect
      immunofluorescence that the Tetrahymena TpCCTalpha, TpCCTdelta, TpCCTepsilon, and
      TpCCTeta-subunits colocalize with tubulin in cilia, basal bodies, oral apparatus,
      and contractile vacuole pores. TpCCT-subunits localization was affected during
      reciliation. These findings combined with atomic force microscopy measurements in
      reciliating cells indicate that these proteins play a role during cilia
      biogenesis related to microtubule nucleation, tubulin transport, and/or axoneme
      assembly. The TpCCT-subunits were also found to be associated with cortex and
      cytoplasmic microtubules suggesting that they can act as microtubule-associated
      proteins. The TpCCTdelta being the only subunit found associated with the
      macronuclear envelope indicates that it has functions outside of the 900 kDa
      complex. Tetrahymena cytoplasm contains granular/globular-structures of TpCCT
      subunits in close association with microtubule arrays. Studies of reciliation and
      with cycloheximide suggest that these structures may be sites of translation and
      folding. Combined biochemical techniques revealed that reciliation affects the
      oligomeric state of TpCCT-subunits being tubulin preferentially associated with
      smaller CCT oligomeric species in early stages of reciliation. Collectively,
      these findings indicate that the oligomeric state of CCT-subunits reflects the
      translation capacity of the cell and microtubules integrity.

PMID- 14567990
TI  - Rab11b resides in a vesicular compartment distinct from Rab11a in parietal cells
      and other epithelial cells.
AB  - The Rab11 family of small GTPases is composed of three members, Rab11a, Rab11b,
      and Rab25. While recent work on Rab11a and Rab25 has yielded some insights into
      their function, Rab11b has received little attention. Therefore, we sought to
      examine the distribution of endogenous Rab11b in epithelial cells. In rabbit
      gastric parietal cells, unlike Rab11a, Rab11b did not colocalize or coisolate
      with H(+)/K(+)-ATPase. In MDCK cells, endogenous Rab11b localized to an apical
      pericentrisomal region distinct from Rab11a. The microtubule agents nocodazole
      and taxol dramatically alter Rab11a's localization in the cell, while effects on
      Rab11b's distribution were less apparent. These results indicate that in contrast
      to Rab11a, the Rab11b compartment in the apical region is not as dependent upon
      microtubules. While Rab11a is known to regulate transferrin trafficking in
      nonpolarized cells and IgA trafficking in polarized cells, Rab11b exhibited
      little colocalization with either of these cargoes. Thus, while Rab11a and Rab11b
      share high sequence homology, they appear to reside within distinct vesicle
      compartments.

PMID- 14567991
TI  - Carbonic anhydrase IX reduces E-cadherin-mediated adhesion of MDCK cells via
      interaction with beta-catenin.
AB  - Carbonic anhydrase IX (CA IX) is a cancer-associated transmembrane isoform of
      zinc metalloenzymes that catalyse interconversion between carbon dioxide and
      bicarbonate. CA IX is strongly induced by tumor hypoxia and has been proposed to
      participate in acidification of tumor microenvironment and in cell adhesion. To
      elucidate the cell adhesion-related role of CA IX, we investigated its
      subcellular localization and relationship to E-cadherin, a key adhesion molecule
      whose loss or destabilization is linked to tumor invasion. For this purpose, we
      generated MDCK cells with constitutive expression of human CA IX protein. During
      the monolayer formation, CA IX was localized to cell-cell contacts and its
      distribution in lateral membranes overlapped with E-cadherin. Calcium switch
      triggered disruption and reconstitution of cell contacts resulted in
      relocalization of both CA IX and E-cadherin to cytoplasm and back to plasma
      membrane. A similar phenomenon was observed in hypoxia-treated and reoxygenated
      cells. Moreover, CA IX-expressing MDCK cells exhibited reduced cell adhesion
      capacity and lower levels of Triton-insoluble E-cadherin. Finally, CA IX was
      found to coprecipitate with beta-catenin. We conclude that CA IX has a capacity
      to modulate E-cadherin-mediated cell adhesion via interaction with beta-catenin,
      which could be of potential significance in hypoxia-induced tumor progression.

PMID- 14567992
TI  - Intraclonal plasticity for bone, smooth muscle, and adipocyte lineages in bone
      marrow stroma fibroblastoid cells.
AB  - Bone marrow stroma fibroblastoid cells (BMSFC) develop from a single clone of
      cells within each of the in vitro fibroblastoid colonies (CFU-F) derived from
      either murine or human bone marrow. All of the clones represented by these
      colonies displayed antigenic and product markers for osteoblast, smooth muscle,
      and adipocyte lineages when tested separately for each marker. Separate sets of
      fibroblastoid colonies derived from the same individual donor's culture tested
      positive with antibodies specific for smooth muscle-specific heavy chain myosin
      (SMMHC), smooth muscle alpha actin-1, bone sialoprotein, osteocalcin, or alkaline
      phosphatase, and developed von Kossa-positive deposits shown by X-ray
      microanalysis and electron diffraction to be hydroxyapatite. Individual cells
      were positive for both SMMHC and osteocalcin. All cells in the multiple clones
      tested were capable of metabolizing a fatty acid to form intracellular lipid
      droplets. PCR transcripts obtained from the human cell cultures that provided
      these BMSFC clones were consistent with the immunocytochemical findings.
      Transcripts for PPAR (gamma)-2 and Cbfa-1 were dependent upon the culture medium
      content, suggesting an osteoblast/adipocyte differentiation switch point. Cell
      lineage specificity for markers and RNA transcripts was determined by comparison
      to skin fibroblast controls. These findings demonstrate a high degree of
      interlineage plasticity in vitro for BMSFC.

PMID- 14567993
TI  - The spatial organization of centromeric heterochromatin during normal human
      lymphopoiesis: evidence for ontogenically determined spatial patterns.
AB  - It is believed that pericentromeric heterochromatin may play a major role in the
      epigenetic regulation of gene expression. We have previously shown that
      centromeres in human peripheral blood cells aggregate into distinct "myeloid" and
      "lymphoid" spatial patterns, suggesting that the three-dimensional organization
      of centromeric heterochromatin in interphase may be ontogenically determined
      during hematopoietic differentiation. To investigate this possibility, the
      spatial patterns of association of different centromeres were analyzed in
      hematopoietic progenitors and compared with those in early-B and early-T cells,
      mature B and T lymphocytes, and, additionally, mature granulocytes and monocytes.
      We show that those patterns change during lymphoid differentiation, with major
      spatial arrangements taking place at different stages during T and B cell
      differentiation. Heritable patterns of centromere association are observed, which
      can occur either at the level of the common lymphoid progenitor, or in early-T or
      early-B committed cells. A correlation of the observed patterns of centromere
      association with the gene content of the respective chromosomes further suggests
      that the variation in the composition of these heterochromatic structures may
      contribute to the dynamic relocation of genes in different nuclear compartments
      during cell differentiation, which might have functional implications for cell
      stage-specific gene expression.

PMID- 14567994
TI  - Osteogenic differentiation of the mesenchymal progenitor cells, Kusa is
      suppressed by Notch signaling.
AB  - Notch receptor plays a crucial role in proliferation and differentiation of many
      cell types. To elucidate the function of Notch signaling in osteogenesis, we
      transfected the constitutively active Notch1 (Notch intracellular domain, NICD)
      into two different osteoblastic mesenchymal cell lines, KusaA and KusaO, and
      examined the changes of their osteogenic potentials. In NICD stable transformants
      (KusaA(NICD) and KusaO(NICD)), osteogenic properties including alkaline
      phosphatase activity, expression of osteocalcin and type I collagen, and in vitro
      calcification were suppressed. Transient transfection of NICD attenuated the
      promoter activities of Cbfa1 and Ose2 element. KusaA was capable of forming
      trabecular bone-like tissues when injected into mouse abdomen, but this in vivo
      bone forming activity was significantly suppressed in KusaA(NICD). Osteoclasts
      were induced in the KusaA-derived bone-like tissues, but lacked in the
      KusaA(NICD)-derived tissues. These results suggest that Notch signaling
      suppresses the osteoblastic differentiation of mesenchymal progenitor cells.

PMID- 14567995
TI  - Cellular aging-dependent decrease in cholesterol in membrane microdomains of
      human diploid fibroblasts.
AB  - Recently it has been shown that cholesterol plays indispensable roles in the
      function of cholesterol-rich microdomains (rafts), such as in ligand-mediated
      signal transduction. Using a perfringolysin O derivative (BCtheta) that binds
      selectively to cholesterol in rafts without causing membrane damage (Proc. Natl.
      Acad. Sci. USA 98 (2001) 4926), we have investigated the effect of in vitro
      replicative aging of human diploid fibroblasts, TIG-1, on the distribution of
      plasma membrane cholesterol. The amount of BCtheta-labeled membrane cholesterol
      decreased during replicative aging of TIG-1 cells, whereas total cholesterol
      increased somewhat. The relationship was confirmed by double staining with
      BCtheta and senescence-associated-beta-galactosidase, a biomarker of senescent
      cells. Cell fractionation experiments revealed decreases in both cholesterol in
      rafts and a raft marker, flotillin, during replicative aging. In addition,
      hydroxyurea-induced prematurely senescent cells also showed a lower level of
      BCtheta-labeled cholesterol than untreated cells, despite maintaining the total
      amount of cholesterol. When TIG-1 cells were cultured in cholesterol-deficient
      medium, BCtheta labeling was first diminished and then premature senescence was
      induced. Taken together with the reduced signaling capacity of aged cells, these
      results suggest that plasma membrane cholesterol in raft microdomains is more
      sensitive to senescence than total cholesterol and is a primary target in aging.

PMID- 14567996
TI  - Hepatocyte growth factor signaling regulates transactivation of genes belonging
      to the plasminogen activation system via hypoxia inducible factor-1.
AB  - Hepatocyte growth factor (HGF) plays an important role in tumor growth and
      progression also by regulating invasive/metastatic phenotype and angiogenesis.
      Here we report that a molecular mechanism possibly contributing to these
      functions of HGF may be hypoxia inducible factor-1 (HIF-1)-dependent expression
      of genes of the plasminogen activation system. The following findings support
      this conclusion: (1) HGF enhanced the activity of a luciferase reporter construct
      under the control of multiple HIF-1 responsive elements (HRE) in HepG2 cells, and
      the cotransfection of the dominant negative for the beta-subunit (ARNT) prevented
      this increase; (2) HGF activated uPA and PAI-1 promoters through HIF-1 activity
      regulated by PI3K/JNK1 transducers, as demonstrated by cotransfection with the
      reporter gene promoters and the dominant negative for ARNT, p85 subunit of PI3K
      or JNK1; (3) hypoxia was additive to HGF in increasing reporter vector
      activities, but probably through different transduction pathways; (4) JNK1 wild
      type expression vector increased HIF-1alpha protein expression probably in a
      phosphorylated state and, thus, functional for transactivating activity; and (5)
      c-Jun did not seem to be involved in the activation of the luciferase construct
      containing multiple HREs because it was not prevented by expression of TAM-67,
      which is the dominant negative mutant form for c-Jun.

PMID- 14567997
TI  - Characterization of the novel amplified in breast cancer-1 (NABC1) gene product.
AB  - Positional cloning of the cancer-associated 20q13.2 amplicon identified two genes
      that display high mRNA levels in breast tumors and here we report the initial
      characterization of one of these gene products, designated Novel Amplified in
      Breast Cancer-1 (NABC1). Analysis of the primary structure of the NABC1 protein
      uncovered two regions of this protein with a high likelihood of forming coiled
      coils and assembly of a mouse NABC1 cDNA showed that this protein is conserved
      between mouse and man. NABC1 antisera showed that, like its transcript, breast
      tumor lines that harbor amplification of 20q13.2 display high levels of the NABC1
      protein compared to normal human fibroblasts or a breast cancer line that does
      not overexpress the NABC1 mRNA. Further, we conclude from studies using in vivo
      and in vitro approaches that the NABC1 protein forms detergent stable homodimers,
      and it is this homodimeric form that accumulates in cells that overexpress this
      protein. NABC1 mRNA exhibits a limited expression pattern in human tissue with
      high relative transcript levels observed only in brain and prostate.
      Immunofluorescence microscopy indicates NABC1 displays a punctate localization
      pattern in the cytoplasm of cultured cells, but biochemical fractionation
      indicates that this protein is not an integral component of membranous
      cytoplasmic organelles. Finally, overexpression of human NABC1 in mouse NIH/3T3
      cells did not affect either the growth rate or anchorage-dependent growth
      properties, suggesting that NABC1 is not a prototypical oncogene.

PMID- 14567999
TI  - Myriadenolide, a labdane diterpene isolated from Alomia myriadenia (asteraceae)
      induces depolarization of mitochondrial membranes and apoptosis associated with
      activation of caspases-8, -9, and -3 in Jurkat and THP-1 cells.
AB  - Myriadenolide is a diterpene that we have recently isolated from the extract of
      Alomia myriadenia (Asteraceae). Here we show for the first time that
      myriadenolide has caspase-dependent cytotoxic activity against human leukemia
      cells from both lymphocytic (Jurkat) and monocytic (THP-1) lineages, because
      preincubation of Jurkat or THP-1 cells with the broad-spectrum caspase inhibitor
      z-VAD-fmk completely abrogated cell death. Moreover, the mitochondrial pathway is
      implicated as mitochondrial depolarization and caspase-9 and caspase-3 activation
      were observed. Interestingly, caspase-8 and cleavage of the proapoptotic member
      of the Bcl-2 family BID was also observed during apoptosis induced by
      myriadenolide, suggesting a role for the caspase-8/BID pathway. However,
      interference with Fas or TNFR1 signaling did not interfere with apoptosis in our
      experimental system. Furthermore, pretreatment of cells with the caspase-3
      inhibitor DEVD-fmk completely blocked the activation of caspase-8, suggesting
      that the activation of the caspase-8/BID pathway is part of an amplification loop
      initiated by caspase-3. Taken together, our results indicate myriadenolide as a
      novel candidate for the treatment of hematological malignancies.

PMID- 14567998
TI  - EWS/FLI function varies in different cellular backgrounds.
AB  - EWS/FLI and other EWS/ets chimeric transcription factors play a central role in
      the biology of the Ewing family tumors. As with many oncogenes, EWS/FLI biologic
      activity can be demonstrated in a limited range of cellular contexts. To
      investigate the causes of this restriction, we demonstrate that two immortalized
      fibroblast lines resistant to EWS/FLI transformation, Rat1 and Yal7, express
      stable levels of EWS/FLI protein. Despite their resistance to EWS/FLI, Rat1 and
      Yal7 can be transformed by the potent EWS/FLI downstream mediator PDGF-C. In
      contrast to NIH3T3, the EWS/FLI resistant lines show no upregulation of PDGF-C in
      response to EWS/FLI, demonstrating differential EWS/FLI function in different
      cellular backgrounds. This phenomenon of differential function can also be
      demonstrated for several other NIH3T3 targets of EWS/FLI. Despite the correlation
      between anchorage-independent growth and PDGF-C induction, PDGF-C does not fully
      reproduce all aspects of the EWS/FLI phenotype in NIH3T3 cells. These results
      further point to the importance of PDGF-C in mediating EWS/FLI in vitro
      transformation and suggest caution in assuming that a transcription factor will
      produce identical effects in different cellular backgrounds.

PMID- 14568000
TI  - Elevated levels of polyamines alter chromatin in murine skin and tumors without
      global changes in nucleosome acetylation.
AB  - Polyamines affect nucleosome oligomerization and DNA conformation in vitro, yet
      little information exists regarding the influence of naturally synthesized
      polyamines on mammalian chromatin. Capitalizing on the relative inefficiency of a
      moderate ionic strength extraction buffer to dissociate histones, we obtained
      evidence of altered chromatin in transgenic mice that overexpress ornithine
      decarboxylase (ODC), which catalyzes polyamine synthesis. Dissociation of
      histones from chromatin in ODC transgenic mouse skin, as well as in tumors that
      develop spontaneously in ODC/Ras bigenic mice, is dramatically reduced relative
      to normal littermate skin. This could reflect tighter tethering of nucleosomes to
      DNA or a more compacted chromatin structure due to elevated intracellular
      concentrations of polyamines since this effect is reversible upon treatment with
      alpha-difluoromethylornithine (DFMO), a specific inhibitor of ODC enzymatic
      activity. Impeded release of nonhistone chromatin proteins HP-1beta and
      nucleophosmin, but not Lamin B, HDAC-1, HMGB, HMGN2, or HMGA1, suggests that
      polyamines exert selective effects on specific chromatin protein complexes.
      Moreover, overall acetylation, as well as specific methylation, of nucleosomes in
      ODC mice is unaffected, implying that access by histone modifying enzymes is not
      generally restricted. The abnormal chromatin environment fostered by elevated
      levels of polyamines may be a necessary prerequisite for epithelial tumor growth
      and maintenance.

PMID- 14568001
TI  - Galardin (GM 6001), a broad-spectrum matrix metalloproteinase inhibitor, blocks
      bombesin- and LPA-induced EGF receptor transactivation and DNA synthesis in rat-1
      cells.
AB  - Matrix metalloproteinases (MMPs) have been implicated in the transactivation of
      the epidermal growth factor receptor (EGFR) induced by G-protein coupled receptor
      (GPCR) agonists. Although EGFR phosphorylation and downstream signaling have been
      shown to be dependent on MMP activity in many systems, a role for MMPs in GPCR
      induced DNA synthesis has not been studied in any detail. In this study we
      utilized the broad-spectrum matrix metalloproteinase inhibitor, galardin
      (Ilomastat, GM 6001), to study the mechanism of bombesin- or LPA-induced EGFR
      transactivation and the role of MMPs in early and late response mitogenic
      signaling in Rat-1 cells stably transfected with the bombesin/GRP receptor (BoR
      15 cells). Addition of galardin to cells stimulated with bombesin or LPA
      specifically inhibited total EGFR phosphorylation, as well as site-specific
      phosphorylation of tyrosine 845, a putative Src phosphorylation site, and
      tyrosine 1068, a typical autophosphorylation site. Galardin treatment also
      inhibited extracellular signal-regulated kinase (ERK) activation induced by
      bombesin or LPA, but not by EGF. In addition, galardin inhibited bombesin- or LPA
      induced DNA synthesis in a dose dependent manner, when stimulated by increasing
      concentrations of bombesin, and when added after bombesin stimulation.
      Furthermore, addition of galardin post-bombesin stimulation indicated that by 3 h
      sufficient accumulation of EGFR ligands had occurred to continue to induce
      transactivation despite an inhibition of MMP activity. Taken together, our
      results suggest that MMPs act as early as 5 min, and up to around 3 h, to mediate
      GPCR-induced EGFR transactivation, ERK activation, and stimulation of DNA
      synthesis.

PMID- 14568002
TI  - Translocation of beta-catenin into the nucleus independent of interactions with
      FG-rich nucleoporins.
AB  - beta-Catenin nuclear import has been found to be independent of classical nuclear
      localization signal (NLS) nuclear import factors. Here, we test the hypothesis
      that beta-catenin interacts directly with nuclear pore proteins to mediate its
      own transport. We show that beta-catenin, unlike importin-beta, does not interact
      detectably with Phe/Gly(FG)-repeat-rich nuclear pore proteins or nucleoporins
      (Nups). Moreover, unlike NLS-containing proteins, beta-catenin nuclear import is
      not inhibited by wheat germ agglutinin (WGA) or excess importin-beta. These
      results suggest beta-catenin nuclear translocation does not involve direct
      interactions with FG-Nups. However, beta-catenin has two regions that can target
      it to the nucleus, and its import is cold sensitive, indicating that beta-catenin
      nuclear import is still an active process. Transport is blocked by a soluble form
      of the C-cadherin cytoplasmic domain, suggesting that masking of the nuclear
      targeting signal may be a mechanism of regulating beta-catenin subcellular
      localization.

PMID- 14568003
TI  - Intervention against the Maillard reaction in vivo.
AB  - The field of Maillard/glycation reactions in vivo has grown enormously during the
      past 20 years, going from 25 to 500 publications per year. It is now well
      recognized that many of the "advanced" products form oxidatively or anaerobically
      and can have deleterious effects on macromolecular and biological function. The
      feasibility of developing pharmacological agents with beneficial in vivo
      properties, based on in vitro inhibition of glycation, has been surprisingly
      successful. This Editorial sets the stage for a series of articles by experts in
      the field, who have made key contributions to our understanding of the Maillard
      reaction in vivo.

PMID- 14568004
TI  - Enzymatic deglycation of proteins.
AB  - Reducing sugars such as glucose react with amino groups in proteins to form the
      Amadori product, which can undergo a wide range of chemical modifications and
      form cross-links in tissue proteins. There is growing evidence to suggest that
      accumulation of glycation products is associated with aging and disease
      progression, as in diabetes. Thus, the design and discovery of inhibitors for the
      glycation cascade would potentially offer a promising therapeutic approach for
      the prevention of glycation related diseases, especially diabetes. Two types of
      enzymes, fructosyl lysine oxidase and fructose lysine 3-phosphokinase, catalyze
      the deglycation reaction and generate free amine groups. This paper reviews the
      biochemical properties of these "amadoriase" enzymes, such as structural-function
      relationship, kinetic mechanism, and substrate specificity, as well as their
      biological roles and applications in the protein deglycation.

PMID- 14568005
TI  - Intervention strategies to prevent pathogenetic effects of glycated albumin.
AB  - Modification of proteins by nonenzymatic glycation is one of the underlying
      factors contributory to the development of complications of diabetes. In general,
      the nature of this structural modification falls into two broad categories:
      nonenzymatic glycation per se, which refers to the attachment of free
      carbohydrate to proteins in the Amadori construct, and Advanced Glycation
      Endproducts (AGE), which refers to a heterogeneous group of carbohydrate-modified
      products generated from the Amadori adduct by oxidation, polymerization, and
      other spontaneous reactions. This review will focus on the role of
      nonenzymatically glycated proteins, and in particular glycated serum albumin, in
      the pathogenesis of diabetic complications, and on pharmacologic approaches to
      mitigate their deleterious effects. Potential intervention strategies to lessen
      the influence of AGE-modified proteins, as well as of other contributory
      abnormalities, are discussed elsewhere in this volume.

PMID- 14568006
TI  - Use of aminoguanidine (Pimagedine) to prevent the formation of advanced glycation
      endproducts.
AB  - Aminoguanidine (AG) is a prototype therapeutic agent for the prevention of
      formation of advanced glycation endproducts. It reacts rapidly with alpha,beta
      dicarbonyl compounds such as methylglyoxal, glyoxal, and 3-deoxyglucosone to
      prevent the formation of advanced glycation endproducts (AGEs). The adducts
      formed are substituted 3-amino-1,2,4-triazine derivatives. Inhibition of disease
      mechanisms, particularly vascular complications in experimental diabetes, by AG
      has provided evidence that accumulation of AGEs is a risk factor for disease
      progression. AG has other pharmacological activities, inhibition of nitric oxide
      synthase and semicarbazide-sensitive amine oxidase (SSAO), at pharmacological
      concentrations achieved in vivo for which controls are required in anti-glycation
      studies. AG is a highly reactive nucleophilic reagent that reacts with many
      biological molecules (pyridoxal phosphate, pyruvate, glucose, malondialdehyde,
      and others). Use of high concentrations of AG in vitro brings these reactions and
      related effects into play. It is unadvisable to use concentrations of AG in
      excess of 500 microM if selective prevention of AGE formation is desired. The
      peak plasma concentration of AG in clinical therapy was ca. 50 microM. Clinical
      trial of AG to prevent progression of diabetic nephropathy was terminated early
      due to safety concerns and apparent lack of efficacy. Pharmacological scavenging
      of alpha-oxoaldehydes or stimulation of host alpha-oxoaldehyde detoxification
      remains a worthy therapeutic strategy to prevent diabetic complications and other
      AGE-related disorders.

PMID- 14568007
TI  - Pyridoxamine, an inhibitor of advanced glycation and lipoxidation reactions: a
      novel therapy for treatment of diabetic complications.
AB  - Pyridoxamine (PM), originally described as a post-Amadori inhibitor of formation
      of advanced glycation end-products (AGEs), also inhibits the formation of
      advanced lipoxidation end-products (ALEs) on protein during lipid peroxidation
      reactions. In addition to inhibition of AGE/ALE formation, PM has a strong lipid
      lowering effect in streptozotocin (STZ)-induced diabetic and Zucker obese rats,
      and protects against the development of nephropathy in both animal models. PM
      also inhibits the development of retinopathy and neuropathy in the STZ-diabetic
      rat. Several products of reaction of PM with intermediates in lipid autoxidation
      have been identified in model reactions in vitro and in the urine of diabetic and
      obese rats, confirming the action of PM as an AGE/ALE inhibitor. PM appears to
      act by a mechanism analogous to that of AGE-breakers, by reaction with dicarbonyl
      intermediates in AGE/ALE formation. This review summarizes current knowledge on
      the mechanism of formation of AGE/ALEs, proposes a mechanism of action of PM, and
      summarizes the results of animal model studies on the use of PM for inhibiting
      AGE/ALE formation and development of complications of diabetes and
      hyperlipidemia.

PMID- 14568008
TI  - Angiotensin II receptor blockers and angiotensin converting enzyme inhibitors:
      implication of radical scavenging and transition metal chelation in inhibition of
      advanced glycation end product formation.

PMID- 14568009
TI  - Evolving concepts in advanced glycation, diabetic nephropathy, and diabetic
      vascular disease.
AB  - Advanced glycation endproducts (AGEs) have been postulated to play a role in the
      development of both nephropathy and large vessel disease in diabetes. However, it
      is still not clear which AGE subtypes play a pathogenetic role and which of
      several AGE receptors mediate AGE effects on cells. This review summarises the
      renoprotective effect of inhibitors of AGE formation, including aminoguanidine,
      and of cross-link breakers, including ALT-711, on experimental diabetic
      nephropathy and on mesenteric vascular hypertrophy. It also demonstrates similar
      effects of aminoguanidine and ramipril (an angiotensin converting enzyme
      inhibitor) on fluorescent and immunoassayable AGE levels, renal protein kinase C
      activity, nitrotyrosine expression, lysosomal function, and protein handling in
      experimental diabetes. These findings indicate that inhibition of the renin
      angiotensin system blocks both upstream and downstream pathways leading to tissue
      injury. We postulate that the chemical pathways leading to advanced glycation
      endproduct formation and the renin angiotensin systems may interact through the
      generation of free radicals, induced both by glucose and angiotensin II. There is
      also evidence to suggest that AGE-dependent pathways may play a role in the
      development of tubulointerstitial fibrosis in the diabetic kidney. This effect is
      mediated through RAGE and is TGF-beta and CTGF-dependent.

PMID- 14568010
TI  - Novel inhibitors of advanced glycation endproducts.
AB  - A number of natural or synthetic compounds as AGE inhibitors have been proposed,
      discovered or currently being advanced by others and us. We have identified two
      new classes of aromatic compounds; aryl- (and heterocyclic) ureido and aryl (and
      heterocyclic) carboxamido phenoxyisobutyric acids, and benzoic acid derivatives
      and related compounds, as potential inhibitors of glycation and AGE formation.
      Some of these novel compounds also showed "AGE-breaking" activities in vitro.
      Current evidence is that chelation of transition metals and/or trapping or
      indirect inhibition of formation of reactive carbonyl compounds are involved in
      the mechanisms of action of these novel AGE inhibitors and breakers. Here, we
      review the inhibitors of glycation and AGE-breakers published to date and present
      the results of our in vitro and in vivo investigations on a number of these novel
      AGE inhibitors. These AGE-inhibitors and AGE-breakers may find therapeutic use in
      the treatment of diseases that AGE formation and accumulation may be responsible
      for their pathogenesis such as diabetes, Alzheimer's, rheumatoid arthritis, and
      atherosclerosis.

PMID- 14568011
TI  - Blockade of receptor for advanced glycation endproducts: a new target for
      therapeutic intervention in diabetic complications and inflammatory disorders.
AB  - The glycation and oxidation of proteins/lipids leads to the generation of a new
      class of biologically active moieties, the advanced glycation endproducts (AGEs).
      Recent studies have elucidated that carboxymethyllysine (CML) adducts of
      proteins/lipids are a highly prevalent AGE in vivo. CML-modified adducts are
      signal transduction ligands of the receptor for AGE (RAGE), a member of the
      immunoglobulin superfamily. Importantly, CML-modified adducts accumulate in
      diverse settings. In addition to enhanced formation in settings of high glucose,
      these adducts form in inflammatory milieu. Studies performed both in vitro and in
      vivo have suggested that the proinflammatory/tissue destructive consequences of
      RAGE activation in the diabetic/inflamed environment may be markedly attenuated
      by blockade of the ligand-RAGE axis. Here, we will summarize the known
      consequences of RAGE activation in the tissues and highlight novel areas for
      therapeutic intervention in these disease states.

PMID- 14568012
TI  - Therapeutic potential of breakers of advanced glycation end product-protein
      crosslinks.
AB  - Long-lived structural proteins, collagen and elastin, undergo continual non
      enzymatic crosslinking during aging and in diabetic individuals. This abnormal
      protein crosslinking is mediated by advanced glycation end products (AGEs)
      generated by non-enzymatic glycosylation of proteins by glucose. The AGE-derived
      protein crosslinking of structural proteins contributes to the complications of
      long-term diabetes such as nephropathy, retinopathy, and neuropathy. AGE
      crosslinks have also been implicated in age-related cardiovascular diseases.
      Potential treatment strategies for these AGE-derived complications include
      prevention of AGE-formation and breaking of the existing AGE-crosslinks. The
      therapeutic potential of the AGE-inhibitor, pimagedine (aminoguanidine), has been
      extensively investigated in animal models and in Phase 3 clinical trials. This
      review presents the pre-clinical and clinical studies using ALT-711, a highly
      potent AGE-crosslink breaker that has the ability to reverse already-formed AGE
      crosslinks. Oral administration of ALT-711 has resulted in a rapid improvement in
      the elasticity of stiffened myocardium in experimental animals. Topical
      administration of ALT-711 was effective in improving the skin hydration of aged
      rats. The therapeutic potential of crosslink breakers for cardiovascular
      complications and dermatological alterations associated with aging and diabetes
      is discussed.

PMID- 14568014
TI  - Effects of extracellular atp on axonal transport in cultured mouse dorsal root
      ganglion neurons.
AB  - In primary sensory neurons, extracellular ATP plays important roles in
      nociception and afferent neurotransmission. Here we investigated the effects of
      ATP on axonal transport in cultured adult mouse dorsal root ganglion neurons
      using video-enhanced microscopy. Continuous application (26 min) of ATP (100
      microM) significantly increased axonal transport of membrane-bound organelles in
      anterograde and retrograde directions. All neurons tested (n=5) responded to ATP.
      The number of transported organelles per min began to increase within 2 min and
      peaked at 11-14 min after the start of ATP application, and thereafter gradually
      declined. The peak values in both directions were approximately 140% of the
      initial values before application. The P2 receptor antagonist suramin (1 mM)
      completely blocked the effect of ATP. Uridine 5'-triphosphate (UTP; 100 microM)
      produced a similar effect to ATP, with peak values at 11 min reaching 140% in
      both directions (n=6). ADP (100 microM; n=5), alpha,beta-methylene ATP (100
      microM; n=6), or 2-methylthio ATP (100 microM; n=5) had no effect on axonal
      transport. Our findings indicate that extracellular ATP is able to increase
      axonal transport in primary sensory neurons. The equal potency of ATP and UTP
      with no detectable response to ADP, alpha,beta-methylene ATP, or 2-methylthio ATP
      suggests the possible involvement of P2Y(2) receptors. Extracellular ATP may play
      an important role in the modulation of axonal transport in sensory neurons.

PMID- 14568015
TI  - Nucleus accumbens oxytocin and dopamine interact to regulate pair bond formation
      in female prairie voles.
AB  - Although oxytocin (OT) and dopamine (DA) have been implicated in pair bond
      formation in monogamous prairie voles (Microtus ochrogaster), the nature of
      potential interactions between these two neurochemical systems and the brain
      circuits important for such interactions in the regulation of pair bonding have
      not been explored. Here, we demonstrated that access to both OT and DA D2-type
      receptors is necessary for pair bond formation, as blockade of either type of
      receptor prevented partner preferences induced by OT or a D2-type agonist. We
      also demonstrated that the nucleus accumbens (NAcc) is a brain area important for
      such OT-DA interactions. In NAcc, blockade of OT receptors prevented partner
      preferences induced by a D2-type agonist whereas blockade of D2-type, but not D1
      type, DA receptors blocked OT-induced partner preferences. Together, our data
      suggest that concurrent activation of OT and DA D2-type receptors in NAcc is
      essential for pair bond formation in female prairie voles.

PMID- 14568016
TI  - Neural correlates of sad feelings in healthy girls.
AB  - Emotional development is indisputably one of the cornerstones of personality
      development during infancy. According to the differential emotions theory (DET),
      primary emotions are constituted of three distinct components: the neural
      evaluative, the expressive, and the experiential. The DET further assumes that
      these three components are biologically based and functional nearly from birth.
      Such a view entails that the neural substrate of primary emotions must be similar
      in children and adults. Guided by this assumption of the DET, the present
      functional magnetic resonance imaging study was conducted to identify the neural
      correlates of sad feelings in healthy children. Fourteen healthy girls (aged 8
      10) were scanned while they watched sad film excerpts aimed at externally
      inducing a transient state of sadness (activation task). Emotionally neutral film
      excerpts were also presented to the subjects (reference task). The subtraction of
      the brain activity measured during the viewing of the emotionally neutral film
      excerpts from that noted during the viewing of the sad film excerpts revealed
      that sad feelings were associated with significant bilateral activations of the
      midbrain, the medial prefrontal cortex (Brodmann area [BA] 10), and the anterior
      temporal pole (BA 21). A significant locus of activation was also noted in the
      right ventrolateral prefrontal cortex (BA 47). These results are compatible with
      those of previous functional neuroimaging studies of sadness in adults. They
      suggest that the neural substrate underlying the subjective experience of sadness
      is comparable in children and adults. Such a similitude provides empirical
      support to the DET assumption that the neural substrate of primary emotions is
      biologically based.

PMID- 14568017
TI  - The influence of the extracellular matrix on the morphology and intracellular pH
      of cultured astrocytes exposed to media lacking bicarbonate.
AB  - In previous work we showed that the polygonal shape of hippocampal astrocytes
      cultured on poly-L-lysine changes to a stellate morphology with loss of
      actinomyosin stress fibers on exchanging the culture medium for saline buffered
      with HEPES [Brain Res 946 (2002)12]. By contrast, in bicarbonate-buffered saline
      containing Ca(2+) astrocytes remained polygonal and continued to express stress
      fibers. Evidence suggests that stellation induced by saline buffered with HEPES
      is related to intracellular acidification due to the absence of bicarbonate. Here
      we studied the influence of the matrix used in preparing astrocyte cultures.
      Stellation in HEPES-saline occurred on a matrix of fibronectin, but not on
      matrices of collagen I or IV provided Ca(2+) was present. Laminin partially
      prevented stellation in HEPES-saline. Further, the intracellular acidification
      induced by HEPES-saline observed in astrocytes cultured on polylysine was
      abolished in cells cultured on collagens and was attentuated on a matrix of
      laminin. Two observations suggested the involvement of integrins and focal
      adhesions. (1) Treatment of cultures on collagens with a blocking antibody to the
      beta1 integrin subunit abolished protection against HEPES-induced stellation. (2)
      Compared with polylysine, astrocytes cultured on collagens expressed increased
      contents of phosphotyrosine proteins, focal adhesion proteins vinculin and
      paxillin, the beta1 integrin subunit and increased numbers of focal adhesions
      labelled with anti-vinculin. The observation that astrocytes cultured on collagen
      I or IV, in contrast to polylysine, express stress fibers and a constant
      intracellular pH in the absence of buffering by bicarbonate may be related to the
      fact that in the intact brain astrocytic processes (or end-feet) encounter and
      bind to collagen IV and laminin in the basement membrane of the endothelial cells
      which surround the cerebral capillaries. It is also possible that astrocytes
      retain this capacity from early development when fibrous matrix proteins are
      present.

PMID- 14568018
TI  - A change in the pattern of activity affects the developmental regression of the
      Purkinje cell polyinnervation by climbing fibers in the rat cerebellum.
AB  - Pattern of activity during development is important for the refinement of the
      final architecture of the brain. In the cerebellar cortex, the regression from
      multiple to single climbing fiber innervation of the Purkinje cell occurs during
      development between postnatal days (P) 5 and 15. However, the regression is
      hampered by altering in various ways the morpho-functional integrity of the
      parallel fiber input. In rats we disrupted the normal activity pattern of the
      climbing fiber, the terminal arbor of the inferior olive neurons, by
      administering harmaline for 4 days from P9 to P12. At all studied ages (P15-87)
      after harmaline treatment multiple (double only) climbing fiber EPSC-steps
      persist in 28% of cells as compared with none in the control. The ratio between
      the amplitudes of the larger and the smaller climbing fiber-evoked EPSC increases
      in parallel with the decline of the polyinnervation factor, indicating a gradual
      enlargement of the synaptic contribution of the winning climbing fiber synapse at
      the expense of the losing one. Harmaline treatment had no later effects on the
      climbing fiber EPSC kinetics and I/V relation in Purkinje cells (P15-36).
      However, there was a rise in the paired-pulse depression indicating a
      potentiation of the presynaptic mechanisms. In the same period, after harmaline
      treatment, parallel fiber-Purkinje cell electrophysiology was unaffected. The
      distribution of parallel fiber synaptic boutons was also not changed. Thus, a
      change in the pattern of activity during a narrow developmental period may affect
      climbing fiber-Purkinje cell synapse competition resulting in occurrence of
      multiple innervation at least up to 3 months of age. Our results extend the
      current view on the role of the pattern of activity in the refinement of neuronal
      connections during development. They suggest that many similar results obtained
      by different gene or receptor manipulations might be simply the consequence of
      disrupting the pattern of activity.

PMID- 14568019
TI  - Immunohistochemical localization of myosin Va in the adult rat brain.
AB  - Brain myosin Va (MVa) is a molecular motor associated with plastic changes during
      development. MVa has previously been detected in the cell body and in dendrites
      of neuronal cells in culture, in cells of the guinea-pig cochlea, as well as in
      cerebellar cells. Adult Wistar rats (n=14), 250-300 g, were perfused with
      standard methods for immunohistochemistry, using a polyclonal, affinity-purified
      rabbit antibody against MVa tail domain. Anti-MVa antibody specifically stained
      neuronal nuclei from forebrain to cerebellar regions, and more intensely sensory
      nuclei. Differences in MVa immunoreactivity were detected between brain nuclei,
      ranging from very intense to weak staining. The analysis of MVa and glial
      fibrillary acidic protein staining in adjacent brain sections demonstrated a
      clear-cut neuronal labeling rather than an astroglial staining. The studies
      presented here represent a comprehensive map of MVa regional distribution in the
      CNS of the adult rat and may contribute to the basic understanding of its role in
      brain function and plasticity, particularly in relationship to phenomena that
      involve molecular motors, such as neurite outgrowth, organelle transport and
      neurotransmitter-vesicle cycling. It is important to highlight that this is a
      pioneer immunohistochemical study on the distribution of MVa on the whole brain
      of adult rats, a first step toward the understanding of its function in the CNS.

PMID- 14568020
TI  - Stimulus-induced patterns of bioelectric activity in human neocortical tissue
      recorded by a voltage sensitive dye.
AB  - Stimulus-induced pattern of bioelectric activity in human neocortical tissue was
      investigated by use of the voltage sensitive dye RH795 and a fast optical
      recording system. During control conditions stimulation of layer I evoked
      activity predominantly in supragranular layers showing a spatial extent of up to
      3000 microm along layer III. Stimulation in white matter evoked distinct activity
      in infragranular layers with a spatial extent of up to 3000 microm measured along
      layer V. The mean amplitude of optical signals close to the stimulated sites in
      layer I and white matter determined 25 ms following the stimulus, decreased by
      50% at a lateral distance of approximately 900 microm and 1200 microm,
      respectively. Velocity of spread along the vertical stimulation axis reached 0.24
      m/s in the supragranular layers (layers I to III) and then decreased to 0.09 m/s
      following layer I activation; stimulation of white matter induced a velocity of
      spread in layer V of 0.38 m/s, which slowed down to 0.12 m/s when passing the
      lower border of lamina IV. The horizontal velocities of spread determined from
      the stimulation site to a lateral distance of 500 microm reached 0.26-0.28 m/s
      and 0.28-0.35 m/s for layer I and white matter stimulation, respectively. At
      larger distances velocity of spread decreased. Increased excitability (Mg(2+)
      free solution) had no significant effect on the spatio-temporal distribution of
      evoked activity as compared with control conditions. There were also no obvious
      differences between the results obtained in slices, which generated spontaneously
      sharp waves and those which were not spontaneously active. About 30% of the
      slices (n=7) displayed a greatly different response pattern, which seemed not to
      be related in a simple way to the stimulation as was the case in the majority of
      the investigated slices. The activity pattern of those slices appeared atypical
      in regard to their deviations of the vertical and horizontal extent of activity,
      to their reduced spatial extent of activity during increased excitability, to
      their layer-related distribution of activity, and to the appearance of
      afterdischarges.Concluding, in 30% of the human temporal lobe slices atypical
      activity pattern occurred which obviously reflect intrinsic epileptiform
      properties of the resected tissue. The majority of slices showed stereotyped
      activity pattern without evidence for increased excitability.

PMID- 14568021
TI  - Relationship between expression of multiple drug resistance proteins and p53
      tumor suppressor gene proteins in human brain astrocytes.
AB  - Multiple drug resistance occurs when cells fail to respond to chemotherapy.
      Although it has been established that the drug efflux protein P-glycoprotein
      protects the brain from xenobiotics, the mechanisms involved in the regulation of
      expression of multiple drug resistance genes and proteins are not fully
      understood. Re-entry into the cell cycle and integrity of the p53 signaling
      pathway have been proposed as triggers of multiple drug resistance expression in
      tumor cells. Whether this regulation occurs in non-tumor CNS tissue is not known.
      Since multiple drug resistance overexpression has been reported in glia and blood
      vessels from epileptic brain, we investigated the level of expression of
      multidrug resistance protein, multidrug resistance-associated proteins and lung
      resistance protein in endothelial cells and astrocytes isolated from epileptic
      patients or studied in situ in surgical tissue samples by double label
      immunocytochemistry. Reverse transcriptase-polymerase chain reaction and Western
      blot analyses revealed that multiple drug resistance, multidrug resistance
      protein, and lung resistance protein are expressed in these cells. Given that
      lung resistance proteins have been reported to be preferentially expressed by
      tumors, we investigated expression of tumor suppressor genes in epileptic
      cortices. The pro-apoptotic proteins p53 and p21 could not be detected in
      "epileptic" astrocytes, while endothelial cells from the same samples readily
      expressed these proteins, as did normal brain astroglia and normal endothelial
      cells. Other apoptotic markers were also absent in epileptic glia. Our results
      suggest a possible link between loss of p53 function and expression of multiple
      drug resistance in non-tumor CNS cells.

PMID- 14568022
TI  - Early microglial activation following neonatal excitotoxic brain damage in mice:
      a potential target for neuroprotection.
AB  - Previous studies in a mouse model of neonatal excitotoxic brain damage mimicking
      the brain lesions in human cerebral palsy showed microglial activation within 24
      h after intracerebral injection of the glutamatergic analog ibotenate. Using this
      model, we studied the expression of CD-45 antigen, a marker of blood-derived
      cells, by these activated microglial cells labeled by Griffonia simplicifolia I
      isolectin B4. Immunohistochemistry performed during early development of
      excitotoxic lesions showed that most cells labeled with the isolectin B4 were CD
      45-negative, suggesting that these early activated microglial cells were deriving
      chiefly from resident microglia and not from circulating monocytes. We also
      directly tested the hypothesis that activated resident microglia and/or blood
      derived monocytes play a role in the pathophysiology of excitotoxic brain damage.
      Repeated i.p. administrations of chloroquine, chloroquine+colchicine,
      minocycline, or an anti-MAC1 antibody coupled to the toxin saporin before and/or
      after ibotenate injection induced a significant reduction in the density of
      isolectin B4-positive cells. This inhibition of resident microglial and/or blood
      derived monocytes activation was accompanied by a significant reduction in the
      severity of ibotenate-induced brain lesions (up to 79% lesion size reduction with
      the highest minocycline dose) as well as of ibotenate-induced cortical caspase-3
      activation (49% reduction).

PMID- 14568023
TI  - [3H]-nociceptin ligand-binding and nociceptin opioid receptor mrna expression in
      the human brain.
AB  - Following the cloning of the novel nociceptin opioid receptor (NOP(1)) and the
      identification of its endogenous ligand orphanin FQ/nociceptin the distribution
      and functional role of the NOP(1) receptor system have been studied mainly in the
      rodent CNS. In the present study the regional distribution and splice variant
      expression of the NOP(1) receptor was investigated in the adult human brain using
      [(3)H]-nociceptin autoradiography, NOP(1) reverse transcriptase PCR and mRNA in
      situ hybridization. Ligand binding revealed strong expression of functional
      NOP(1) receptors in the cerebral cortex and moderate signals in hippocampus and
      cerebellum. Interestingly, the NOP(1) receptor specific ligand was also strongly
      bound in the human striatum. A matching pattern of mRNA expression was observed
      with high amounts of NOP(1) mRNA in the prefrontal and cingulate cortex as well
      as in the dentate gyrus of the hippocampus. mRNA levels in the Ammon's horn and
      cerebellar cortex were moderate and low in the striatum. A considerable
      expression of N-terminal NOP(1) splice variant mRNAs was not detectable in the
      human brain by means of in situ hybridization. This suggests that functional
      NOP(1) receptors in the human brain are encoded by N-terminal full length NOP(1)
      transcripts. The present data on the anatomical distribution of nociceptin
      binding sites and NOP(1) receptor mRNA contribute to the knowledge about opioid
      receptor systems in the human brain and may promote the understanding of function
      and pharmacology of the orphanin FQ/nociceptin receptor system in the human CNS.

PMID- 14568024
TI  - Hydrogen peroxide increases the activity of rat sympathetic preganglionic neurons
      in vivo and in vitro.
AB  - Reactive oxygen species (ROS) have been shown to modulate neuronal synaptic
      transmission and have also been implicated in cardiovascular diseases such as
      hypertension. The hypothesis that H(2)O(2) acting on sympathetic preganglionic
      neurons (SPNs) affects spinal sympathetic outflow was tested in the present
      study. H(2)O(2) was applied intrathecally via an implanted cannula to the T7-T9
      segments of urethane-anesthetized rats. Blood pressure and heart rate were used
      as indices to evaluate the spinal sympathetic effects of H(2)O(2) in vivo.
      Intrathecal H(2)O(2) (100-1000 nmol) dose-dependently increased both the mean
      arterial pressure and heart rate. Reproducible pressor effects of H(2)O(2) (1000
      nmol) applied consecutively at intervals of 30 min were observed. The pressor
      effects of intrathecal H(2)O(2) (1000 nmol) were attenuated by pretreatment with
      intrathecal administration of catalase (500 units), or N-acetyl-cysteine (1000
      nmol). The pressor effects of intrathecal H(2)O(2) (1000 nmol) were also
      antagonized dose-dependently by prior intrathecal injection of AP-5 (DL-2-amino-5
      phosphonovaleric acid, 10 and 30 nmol), or 6-cyano-7- nitroquinoxaline-2,3
      dione, 10 and 30 nmol. In vitro electrophysiological study in spinal cord slices
      showed that superfusion of 1 mM H(2)O(2) for 3 min, which had no effect on
      membrane potential, caused an increase in amplitude of excitatory postsynaptic
      potentials in SPNs, but had little effect on that of inhibitory postsynaptic
      potentials. Taken together, these results demonstrated that oxidative stress in
      spinal cord may cause an increase in spinal sympathetic tone by acting on SPNs,
      which may contribute to ROS-induced cardiovascular dysfunction.

PMID- 14568025
TI  - Combined intrastriatal dopamine D1 and serotonin 5-HT2 receptor stimulation
      reveals a mechanism for hyperlocomotion in 6-hydroxydopamine-lesioned rats.
AB  - Loss of dopaminergic innervation to the striatum increases the sensitivity of
      dopamine (DA) D1 and serotonin (5-HT) 5-HT2 receptor signaling. Previous work
      from our laboratory has shown that systemic co-administration of D1 and 5-HT2
      receptor agonists leads to the synergistic overexpression of striatal
      preprotachykinin mRNA levels in the DA-depleted, but not intact animals. In the
      present study, we examined this mechanism as related to locomotor behavior. Adult
      male Sprague-Dawley rats were subject to bilateral i.c.v. 6-hydroxydopamine (6
      OHDA; 200 microg in 10 microl/side) or vehicle (0.9% saline and 0.1% ascorbic
      acid). After 3 weeks, rats were tested for locomotor responses to bilateral
      intrastriatal infusions of vehicle (0.9% NaCl), the D1 agonist SKF82958 [(+/-)6
      chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetra-hydro-(1H)-3-benzazepine
      hydrobromide; 0.1, 1.0 or 10.0 microg/side], the 5-HT2 agonist DOI [(+/-)-1-(4
      iodo-2,5-dimethoxyphenyl)-2-aminopropane; 0.1, 1.0 or 10.0 microg/side] or
      subthreshold doses of DOI and SKF82958 (0.1 microg+0.1 microg in 0.8
      microl/side). Rats with DA loss demonstrated supersensitive locomotor responses
      to SKF82958, but not DOI. Combined administration of subthreshold SKF82958 and
      DOI doses (0.1 microg+0.1 microg) synergistically increased locomotor behavior
      only in 6-OHDA-lesioned rats. These effects were blocked by either the D1
      antagonist SCH23390 3-methyl-1-phenyl-2,3,4,5-tetrahydro-7-chloro-8-hydroxy-(1H)
      3-benzazepine or the 5-HT2 antagonist ritanserin (each 1.0 microg in 0.8
      microl/side). The results of this study suggest that the behavioral synergy
      induced by local co-stimulation of D1 and 5-HT2 receptors within the 6-OHDA
      lesioned striatum may lead to hyperkinesias that can occur with continued
      pharmacological treatment of Parkinson's disease.

PMID- 14568026
TI  - Effects of estrogen and raloxifene on neuroglia number and morphology in the
      hippocampus of aged female mice.
AB  - Hormone replacement therapy with the gonadal steroid estrogen or synthetic agents
      such as raloxifene, a selective estrogen receptor modulator, may affect cellular
      function in brains of postmenopausal women. In vitro studies suggest that 17beta
      estradiol and raloxifene can alter the microglial and astrocyte expression of
      immuno-neuronal modulators, such as cytokines, complement factors, chemokines,
      and other molecules involved in neuroinflammation and neurodegeneration. To
      directly test whether exogenous 17beta estradiol and raloxifene affect the number
      of glial cells in brain, C57BL/6NIA female mice aged 20-24 months received
      bilateral ovariectomy followed by s.c. placement of a 60-day release pellet
      containing 17beta estradiol (1.7 mg), raloxifene (10 mg), or placebo
      (cholesterol). After 60 days, numbers of microglia and astrocytes were quantified
      in dentate gyrus and CA1 regions of the hippocampal formation using
      immunocytochemistry and design-based stereology. The results show that long-term
      17beta estradiol treatment in aged female mice significantly lowered the numbers
      of astrocytes and microglial cells in dentate gyrus and CA1 regions compared with
      placebo. After long-term treatment with raloxifene, a similar reduction was
      observed in numbers of astrocytes and microglial cells in the hippocampal
      formation. These findings indicate that estrogen and selective estrogen receptor
      modulators can influence glial-mediated inflammatory pathways and possibly
      protect against age- and disease-related neuropathology.

PMID- 14568027
TI  - Neurokinin release produced by capsaicin acting on the central terminals and
      axons of primary afferents: relationship with N-methyl-D-aspartate and GABA(B)
      receptors.
AB  - Capsaicin stimulates neurokinin release in the spinal cord when applied both
      centrally and peripherally. To determine whether these two actions have different
      mechanisms, we measured neurokinin 1 receptor (NK1R) internalization in rat
      spinal cord slices elicited by incubating the whole slice or just the dorsal root
      with capsaicin. NK1R internalization produced by incubating the slices with
      capsaicin was abolished by the NK1R antagonist RP-67580, by the vanilloid
      receptor 1 (VR1) antagonist capsazepine, and by eliminating Ca(2+) from the
      medium, but was not affected by the Na(+) channel blocker lidocaine. Therefore,
      the internalization was due to neurokinin release mediated by Ca(2+) entry
      through VR1 receptors, but did not require the firing of action potentials.
      Incubating the root with capsaicin produced NK1R internalization in the
      ipsilateral dorsal horn that was abolished when capsazepine or lidocaine was
      included in, or when Ca(2+) was omitted from, the medium surrounding the root.
      Therefore, the internalization was mediated by Ca(2+) entry in the axons through
      VR1, and required firing of action potentials. The efficacy of capsaicin when
      applied to the root (36+/-3%) was lower than when applied to the slice (91+/-3%),
      but its potency was the same (0.49 microM and 0.37 microM, respectively). We also
      investigated whether presynaptic N-methyl-D-aspartate (NMDA) and GABA(B)
      receptors modulate these two actions of capsaicin. Neither the NMDA receptor
      blocker MK-801 nor the GABA(B) agonist baclofen decreased NK1R internalization
      produced by 1 microM capsaicin applied to the slices, but they inhibited the
      internalization produced by 0.3 microM capsaicin applied to the slices or 1
      microM capsaicin applied to the root. Therefore, capsaicin can produce neurokinin
      release from primary afferents 1) by a direct action on their central terminals
      and 2) by increasing the firing of action potentials on their axons. The first
      effect largely bypasses other modulatory mechanism, but the second does not.

PMID- 14568028
TI  - Intraplantar injection of a cyclooxygenase inhibitor ketorolac reduces
      immunoreactivities of substance P, calcitonin gene-related peptide, and dynorphin
      in the dorsal horn of rats with nerve injury or inflammation.
AB  - We previously reported that partial sciatic nerve ligation (PSNL) dramatically up
      regulates cyclooxygenase 2 (COX2) in injured sciatic nerve, and local injection
      of the COX inhibitor, ketorolac, reverses tactile allodynia and suppresses
      increased phosphorylation of the transcription factor cAMP responsive element
      binding protein [Eur J Neurosci 15 (2002) 1037]. These findings suggest that
      peripheral prostaglandins (PGs) are over-produced and contribute to the central
      plasticity and the maintenance of neuropathic pain after nerve injury. PGs,
      particularly PGE2, are well known to facilitate the release of the pro
      nociceptive neuropeptide substance P (SP) and calcitonin gene-related peptide
      (CGRP) from primary sensory afferents. Thus, suppressing peripheral PG over
      production may inhibit the release of these two neuropeptides from primary
      afferents and thereby increase the content of these neuropeptides remaining in
      afferent terminals in the dorsal horn. In this study we tested this hypothesis by
      examining the immunoreactivities of SP and CGRP in the dorsal horn of PSNL rats
      intraplantarly injected with saline and ketorolac. Four weeks after PSNL, SP- and
      CGRP-immunoreactivities (IR) in the ipsilateral dorsal horn were not
      significantly different from the contralateral side. Five days following
      intraplantar injection of ketorolac, CGRP- and SP-IR in the ipsilateral and
      contralateral dorsal horn were dramatically reduced compared with saline-injected
      PSNL rats. Local ketorolac also suppressed PSNL-induced increase in dynorphin-IR
      in dorsal horn neurons. Since abundant production of PGs during inflammation is
      well documented, we further examined the effect of intraplantar ketorolac on
      neuropeptide expression in the dorsal horn following carrageenan inflammation. We
      observed that co-administration of ketorolac with carrageenan in the hindpaw also
      reduced SP- and dynorphin-IR in the ipsilateral and contralateral dorsal horn.
      These findings are in contrast to our hypothesis, suggesting that peripherally
      over-produced PGs following nerve injury and inflammation possibly contribute to
      the production of SP and CGRP in primary sensory neurons, to the up-regulation of
      dynorphin in the dorsal horn neurons, and finally to the mechanisms of
      neuropathic and inflammation pain.

PMID- 14568029
TI  - Cyclooxygenase 2 in infiltrating inflammatory cells in injured nerve is
      universally up-regulated following various types of peripheral nerve injury.
AB  - We previously reported the up-regulation of cyclooxygenase 2 (COX2) in injured
      sciatic nerve of rats with partial sciatic nerve ligation (PSNL) and the reversal
      of PSNL-elicited tactile allodynia by local injection of the COX inhibitor
      ketorolac [Eur J Neurosci 15 (2002) 1037]. We further asked whether COX2 up
      regulation in injured nerve is a universal phenomenon following various types of
      nerve injury. In the current study, we observed that abundant COX2 immunoreactive
      (IR) cell profiles appeared in injured nerves of rats following spinal nerve
      ligation (SNL), chronic constriction injury (CCI) and complete sciatic nerve
      transection. Most COX2-IR cells were identified as infiltrating macrophages.
      Partial injury induced greater COX2 up-regulation than complete injury. COX2 up
      regulation reached a peak at 2-4 weeks, evidently declined by 3 months and
      disappeared by 7 months postlesion. These findings suggest that up-regulation of
      COX2 in injured nerve is a common event during the initial several months after
      nerve injury. We observed that local ketorolac-elicited anti-allodynia was
      closely associated with the abundance of COX2-IR cells in injured nerve, varying
      with the type of injury and time after injury. The anti-allodynia lasted the
      longest when local ketorolac was given 2-4 weeks after PSNL, CCI and SNL. The
      duration of local ketorolac's anti-allodynia was the longest in CCI rats, which
      also exhibited the most abundant COX2 up-regulation. Local ketorolac's anti
      allodynia lasted much shorter when given 2-3 months after lesion. Local ketorolac
      failed to induce anti-allodynia 7 months after lesion, a time when COX2-IR cells
      completely disappeared from the injured nerve except a few cells at the injury
      site. Our data strongly suggest that during the initial several months after
      nerve injury, peripherally over-produced prostaglandins play an important role in
      the maintenance of neuropathic pain.

PMID- 14568030
TI  - Desynchronisation of spontaneously recurrent experimental seizures proceeds with
      a single rhythm.
AB  - Here we investigate the temporal properties of recurrent seizure-like events
      (SLEs) in a low-[Mg(2+)] model of experimental epilepsy. Simultaneous intra- and
      extracellular electric signals were recorded in the CA3 region of rat hippocampal
      slices whereby cytosolic [Ca(2+)] transients were imaged by fluorescence
      detection. Recurrence pattern analysis was applied to give a measure of synchrony
      of simultaneously recorded intra- and extracellular electric signals and the SLE
      frequencies were extracted by complex wavelet analysis. Slices from the juvenile,
      but not the young adult rats, displayed several high-amplitude triplets of
      electric and [Ca(2+)] transients, termed paroxysmal spikes, followed by an SLE.
      Occurrence of the full-blown SLE was associated with decreased synaptic activity
      between the paroxysmal spikes that were seen as incomplete SLE starting
      sequences. The time series of recurrent SLEs provide evidence for a single SLE
      rhythm as continuously declining from about 200 Hz to below 1 Hz at the onset and
      termination of SLE, respectively, with an intermediate spectral discontinuity,
      tentatively identified with the tonic/clonic transition. All other frequency
      components were the harmonics of the fundamental rhythm, whereby the gamma and
      the theta band oscillations were not detected as separate activities. Recurrence
      showed decreasing temporal synchrony of intra- and extracellular signals during
      the SLE, suggesting that coincidence is destroyed by the SLE. Blockade of gap
      junctions with 200 microM carbenoxolone ceased recurrent SLEs. Release of gap
      junction blockade shortened both SLEs and their tonic phase indicating that
      persistent changes occurred via an altered gap junction coupling. We conclude
      that the initially precise temporal synchrony is gradually destroyed during ictal
      events with a single rhythm of continuously decreasing frequency. Blockade of gap
      junction coupling might prevent epileptic synchronisation.

PMID- 14568031
TI  - The toxicity of tumor necrosis factor-alpha upon cholinergic neurons within the
      nucleus basalis and the role of norepinephrine in the regulation of inflammation:
      implications for Alzheimer's disease.
AB  - Inflammation and reduced forebrain norepinephrine are features of Alzheimer's
      disease that may interact to contribute to the degeneration of specific neural
      systems. We reproduced these conditions within the basal forebrain cholinergic
      system, a region that is vulnerable to degeneration in Alzheimer's disease. Tumor
      necrosis factor-alpha was infused into the basal forebrain of young mice
      pretreated with a norepinephrine neuronal toxin, N-(2-chloroethyl)-N-ethyl-2
      bromobenzylamine (DSP4), with the expectation that the loss of noradrenergic
      input would enhance the loss of cholinergic neurons. The results indicate that
      chronic infusion of tumor necrosis factor-alpha alone significantly decreased
      cortical choline acetyltransferase activity and increased the number of activated
      microglia and astrocytes within the basal forebrain. The loss of forebrain
      norepinephrine following systemic treatment with DSP4 did not alter the level of
      cortical choline acetyltransferase activity or activate microglia but
      significantly activated astrocytes within the basal forebrain. Infusion of tumor
      necrosis factor-alpha into DSP4-pretreated mice also reduced cortical choline
      acetyltransferase activity on the side of the infusion; however, the decline was
      not significantly greater than that produced by the infusion of tumor necrosis
      factor-alpha alone. The neurodegeneration seen may be indirect since a double
      immunofluorescence investigation did not find evidence for the co-existence of
      tumor necrosis factor-alpha type I receptors on choline acetyltransferase
      positive cells in the basal forebrain. The results suggest that noradrenergic
      cell loss in Alzheimer's disease does not augment the consequences of the chronic
      neuroinflammation and does not enhance neurodegeneration of forebrain cholinergic
      neurons.

PMID- 14568032
TI  - Medullary reticulospinal tract mediating a generalized motor inhibition in cats:
      III. Functional organization of spinal interneurons in the lower lumbar segments.
AB  - The previous report of intracellular recording of hindlimb motoneurons in
      decerebrate cats [ 511] has suggested that the following mechanisms are involved
      in a generalized motor inhibition induced by stimulating the medullary reticular
      formation. First, the motor inhibition, which was prominent in the late latency
      (30-80 ms), can be ascribed to the inhibitory effects in parallel to motoneurons
      and to interneuronal transmission in reflex pathways. Second, both a group of
      interneurons receiving inhibition from flexor reflex afferents and a group of Ib
      interneurons mediate the late inhibitory effects upon the motoneurons. To
      substantiate the above mechanisms of motor inhibition we examined the medullary
      stimulus effects upon intracellular (n=55) and extracellular (n=136) activity of
      spinal interneurons recorded from the lower lumbar segments (L6-L7). Single
      pulses or stimulus trains (1-3) pulses, with a duration of 0.2 ms and intensity
      of 20-50 microA) applied to the medullary nucleus reticularis gigantocellularis
      evoked a mixture of excitatory and inhibitory effects with early (<20 ms) and
      late (>30 ms) latencies. The medullary stimulation excited 55 interneurons
      (28.8%) with a late latency. Thirty-nine of the cells, which included 10 Ib
      interneurons, were inhibited by volleys in flexor reflex afferents (FRAs). These
      cells were mainly located in lamina VII of Rexed. On the other hand, the late
      inhibitory effects were observed in 67 interneurons (35.1%), which included cells
      mediating reciprocal Ia inhibition, non-reciprocal group I (Ib) inhibition,
      recurrent inhibition and flexion reflexes. Intracellular recording revealed that
      the late inhibitory effects were due to inhibitory postsynaptic potentials with a
      peak latency of about 50 ms and a duration of 50-60 ms. The inhibitory effects
      were attenuated by volleys in FRAs. Neither excitatory nor inhibitory effects
      with a late latency were observed in 69 (36.1%) cells which were located in the
      intermediate region and dorsal horn. These results suggest the presence of a
      functional organization of the spinal cord with respect to the production of the
      generalized motor inhibition. Lamina VII interneurons that receive inhibition
      from volleys in FRAs possibly mediate the postsynaptic inhibition from the
      medullary reticular formation in parallel to motoneurons and to interneurons in
      reflex pathways.

PMID- 14568033
TI  - Basolateral amygdala lesions impair both cue- and cocaine-induced reinstatement
      in animals trained on a discriminative stimulus task.
AB  - Drug-associated environmental cues can maintain drug use and contribute to
      relapse even after long periods of abstinence. We investigated the ability of
      sensory stimuli that signaled periods of reward availability to sustain cocaine
      self-administration and trigger the reinstatement of reward-seeking behavior. We
      demonstrate that lesions of the basolateral amygdala (BLA), a structure strongly
      implicated in attributing salience to environmental stimuli, significantly
      reduced the power of predictive cues to elicit reward-seeking behavior. In daily
      training sessions, a 20 s discriminative stimulus (DS) was presented to rats on a
      variable interval schedule. If five lever presses were recorded during the DS-on
      period, then cocaine (0.5 mg/kg) and a conditioned stimulus (CS) were
      simultaneously delivered. After training, half the animals received excitotoxic
      lesions of the BLA with quinolinic acid; the other half received saline. Compared
      with sham-lesioned animals, rats with BLA lesions earned fewer cocaine injections
      and were less accurate in responding to the DS in the first few days following
      the lesion. However, they maintained the same cocaine intake as sham-lesioned
      animals when the DS requirement was lifted. Finally, after seven extinction
      sessions, reinstatement was measured in response to: 1) i.v. cocaine infusion, 2)
      DS, 3) CS, 4) a familiar, but non-rewarded cue (S-) or 5) no stimulus. In sham
      lesioned animals, cocaine and the DS, but not the CS or the S-, triggered
      reinstatement. BLA lesions abolished DS-induced reinstatement and significantly
      attenuated cocaine-induced reinstatement. These results demonstrate 1) that when
      tested under the same conditions, a discriminative cue which signals reward
      availability is a more robust trigger of reward-seeking than a Pavlovian CS which
      signals reward delivery and 2) that the BLA contributes to reinstatement in
      response to these discriminative cues.

PMID- 14568034
TI  - Temporal pattern of hippocampal high-frequency oscillations during sleep after
      stimulant-evoked waking.
AB  - Hippocampal ripple oscillations (140-200 Hz) are believed to be critically
      involved in the consolidation of memory traces during slow-wave sleep (SWS). We
      investigated the temporal pattern of ripple occurrence in relation to sleep
      phases following different types of waking. Amphetamine, the atypical wakening
      drug modafinil or non-pharmacological sleep deprivation lead to an increased
      ripple occurrence ("rebound") during the subsequent SWS episode. Waking of the
      same duration evoked by amphetamine or sleep deprivation led to a ripple rebound
      of similar extent (approximately 200%). The mean intraripple frequency was also
      elevated by up to 20 Hz during SWS following all treatments. Ripple amplitude was
      significantly increased only in experiments with amphetamine. Ripple occurrence
      but not intraripple frequency clearly correlated with the antecedent waking
      duration independent of treatment. Recovery of ripple occurrence and frequency to
      the pretreatment level during SWS depended on SWS duration. At the end of the
      recovery period paradoxical sleep (PS) acted like waking, elevating ripple
      occurrence during subsequent SWS episodes. On the other hand, PS decreased ripple
      occurrence if recovery from the rebound was not yet complete. Thus occurrence and
      structure of ripple oscillations are regulated by the timing and duration of
      previous SWS, PS and waking episodes.

PMID- 14568035
TI  - Brainstem prolactin-releasing peptide neurons are sensitive to stress and
      lactation.
AB  - Prolactin-releasing peptide (PrRP) was originally thought to participate in the
      control of adenohypophyseal prolactin secretion, but its predominant expression
      in a subset of medullary noradrenergic neurons is more in line with roles in
      interoceptive and/or somatosensory information processing. To better define
      functional contexts for this peptide system, immuno- and hybridization
      histochemical methods were used to monitor the capacity of PrRP neurons to
      display activational responses to lactation, suckling, acute footshock or
      hypotensive hemorrhage. PrRP mRNA signal was reduced in the medulla of lactating
      dams, relative to both male and diestrus female controls, with cell counts
      revealing 42% and 43% reductions in the number of positively hybridized cells in
      the nucleus of the solitary tract (NTS) and ventrolateral medulla, respectively.
      Lactating mothers killed after a 90 min suckling episode (following 4 h pup
      removal) failed to show induced Fos expression in identified medullary PrRP
      neurons, despite the fact that responsive neurons were detected in other aspects
      of the caudal NTS. By contrast, acute exposure to hypotensive (25%) hemorrhage or
      footshock each activated substantial complements of medullary neurons expressing
      PrRP mRNA. A substantially greater fraction of the total medullary PrRP
      population exhibited sensitivity to footshock than hemorrhage (71 versus 39%,
      respectively). These results suggest that medullary PrRP neurons are negatively
      regulated by (presumably hormonal) changes in lactation, and are not recruited to
      activation by suckling stimuli. These populations exhibit differential
      sensitivity to distinct acute stressors, and may participate in the modulation of
      adaptive neuroendocrine and autonomic responses to each.

PMID- 14568036
TI  - Neuregulin-1beta modulates in vivo entorhinal-hippocampal synaptic transmission
      in adult rats.
AB  - Neuregulin-1 (NRG-1) proteins and their erbB receptors are essential for neuronal
      development during embryogenesis and may contribute importantly to neuronal
      function in the adult brain. This study tests the hypothesis that NRG-1beta acts
      as a modulator of synaptic activity in the adult brain, specifically at
      hippocampal formation synapses. Adult, male Sprague-Dawley rats were anesthetized
      and a recording electrode with an attached stainless steel microinjector was
      stereotaxically positioned to record field potentials (fEPSP) in either the
      dentate gyrus or the cornu ammonis (CA) 1 field of the hippocampus. The
      entorhinal cortex was continuously stimulated via a paired stainless steel
      electrode. Microinjection of NRG-1beta significantly increased the slope of the
      fEPSP in the dentate gyrus in a dose-dependent manner. Compared with a low dose
      (20 nM), a high dose (100 nM) of NRG-1beta induced a shorter latency response
      that was of greater magnitude. Responses to NRG-1beta were abolished by
      pretreatment with a selective, reversible erbB tyrosine kinase inhibitor,
      PD158780 (100 microM). Further, PD158780 (100 microM) itself significantly
      decreased the entorhinal-dentate fESPS slope by about 15%. Neither equimolar (100
      nM) nor hypermolar (100 microM) sucrose or heat-inactivated NRG-1beta (100 nM)
      significantly altered the entorhinal-dentate fEPSP slope. In contrast to its
      effect at the entorhinal-dentate synapse, NRG-1beta (100 nM) depressed, and
      PD158780 potentiated entorhinal-CA1 synaptic transmission. Thus, in adult rats
      NRG-1beta potentiates transmission at the entorhinal-dentate synapse but
      suppresses transmission at the entorhinal-CA1 synapse. These observations
      indicate that NRG-1 is not only a developmental growth factor, but also modifies
      synaptic transmission in adult rat brain.

PMID- 14568037
TI  - Long-term effects of maternal separation on ethanol intake and brain opioid and
      dopamine receptors in male Wistar rats.
AB  - Accumulating evidence indicates that an animal's response to a drug can be
      profoundly affected by early environmental influences. The brain opioid and
      dopamine systems may play a critical role in these effects, since various types
      of stress and drugs of abuse promote alterations in these brain systems. To study
      this further, we investigated long-term behavioural and neurochemical effects of
      repeated maternal separation in male Wistar rats. The pups were separated in
      litters daily from their dams for either 15 min (MS15) or 360 min (MS360) from
      postnatal days 1-21. Analysis of the kappa- and delta-opioid, dopamine D(1)- and
      D(2)-like receptors with receptor autoradiography revealed long-term
      neurochemical changes in several brain areas. D(1)-like receptor binding was
      affected in the hippocampus and D(2)-like receptor binding in the ventral
      tegmental area and the periaqueductal gray, whereas minor changes were seen in
      opioid receptor density after maternal separation. At 10-13 weeks of age, MS15
      rats had a lower ethanol intake whereas, the MS360 rats consumed more 8% ethanol
      solution compared with MS15 and animal facility-reared rats. Ethanol consumption
      altered kappa-receptor density in several brain areas, for example the amygdala,
      substantia nigra and the periaqueductal gray. D(1)-like receptor binding was
      affected in distinct brain areas, including the nucleus accumbens, where also
      delta-opioid receptor density was changed in addition to the frontal cortex.
      Ethanol-induced changes were observed in D(2)-like receptor density in the
      ventral tegmental area in MS360, and in the ventral tegmental area and frontal
      parietal cortex in animal facility-reared rats. These findings show that early
      experiences can induce long-lasting changes in especially brain dopamine receptor
      density and that ethanol consumption induces alterations in opioid and dopamine
      receptor density in distinct brain areas. It is also suggested that changes
      induced by repeated MS15 may provide protection against high voluntary ethanol
      intake.

PMID- 14568038
TI  - Song activation by testosterone is associated with an increased catecholaminergic
      innervation of the song control system in female canaries.
AB  - In canaries, singing and a large number of morphological features of the neural
      system that mediates the learning, perception and production of song exhibit
      marked sex differences. Although these differences have been mainly attributed to
      sex-specific patterns of the action of testosterone and its metabolites, the
      mechanisms by which sex steroids regulate brain and behavior are far from being
      completely understood. Given that the density of immunoreactive catecholaminergic
      fibers that innervate telencephalic song nuclei in canaries is higher in males,
      which sing, than in females, which usually do not sing, we hypothesized that some
      of the effects induced by testosterone on song behavior are mediated through the
      action of the steroid on the catecholaminergic neurons which innervate the song
      control nuclei. Therefore, we investigated in female canaries the effects of a
      treatment with exogenous testosterone on song production, on the volume of song
      control nuclei, and on the catecholaminergic innervation of these nuclei as
      assessed by immunocytochemical visualization of tyrosine hydroxylase.
      Testosterone induced male-like singing in all females and increased by about 80%
      the volume of two telencephalic song control nuclei, the high vocal center (HVC)
      and the nucleus robustus archistriatalis (RA). Testosterone also significantly
      increased the fractional area covered by tyrosine hydroxylase-immunoreactive
      structures (fibers and varicosities) in most telencephalic song control nuclei
      (HVC, the lateral and medial parts of the magnocellular nucleus of the anterior
      neostriatum, the nucleus interfacialis, and to a lesser extent RA). By contrast,
      testosterone did not affect the catecholaminergic innervation of the
      telencephalic areas adjacent to HVC and RA. Together these data demonstrate that,
      in parallel to its effects on song behavior and on the morphology of the song
      control system, testosterone also regulates the catecholaminergic innervation of
      most telencephalic song control nuclei in canaries. The endocrine regulation of
      singing may thus involve the neuromodulatory action of specialized dopaminergic
      and/or noradrenergic projections onto several key parts of the song control
      system.

PMID- 14568039
TI  - Glial cell line-derived neurotrophic factor normalizes neurochemical changes in
      injured dorsal root ganglion neurons and prevents the expression of experimental
      neuropathic pain.
AB  - Glial cell line-derived neurotrophic factor (GDNF) is necessary for the
      development of sensory neurons, and appears to be critical for the survival of
      dorsal root ganglion (DRG) cells that bind the lectin IB4. Intrathecal infusion
      of GDNF has been shown to prevent and reverse the behavioral expression of
      experimental neuropathic pain arising from injury to spinal nerves. This effect
      of GDNF has been attributed to a blockade of the expression of the voltage gated,
      tetrodotoxin-sensitive sodium channel subtype, Na(V)1.3, in the injured DRG. Here
      we report that GDNF given intrathecally via osmotic-pump to nerve-injured rats
      (L5/L6 spinal nerve ligation) prevented the changes in a variety of neurochemical
      markers in the DRG upon injury. They include a loss of binding of IB4,
      downregulation of the purinergic receptor P2X(3), upregulation of galanin and
      neuropeptide Y immunoreactivity in large diameter DRG cells, and expression of
      the transcription factor ATF3. GDNF infusion concomitantly prevented the
      development of spinal nerve ligation-induced tactile hypersensitivity and thermal
      hyperalgesia. These observations suggest that high dose, exogenous GDNF has a
      broad neuroprotective role in injured primary afferent. The receptor(s) that
      mediates these effects of GDNF is not known. GDNF's ability to block neuropathic
      pain states is not likely to be specific to Na(V)1.3 expression.

PMID- 14568040
TI  - Endotoxin inactivation by selected drinking water treatment oxidants.
AB  - Exposure to endotoxins in treated drinking water can occur through ingestion,
      dermal abrasions, inhalation of water vapor, intravenous injection or during
      dialysis. While the risks associated with endotoxin ingestion and entry through
      dermal abrasions are not well quantified, adverse effects of intravenous
      injection and dialysis are well known and some studies indicate that inhalation
      of moisture-laden air may impact human health. This study quantifies the
      inactivation of endotoxin derived from Escherichia coli O55:B5 by three
      substances used either as disinfectants or oxidants in drinking water treatment:
      chlorine, monochloramine and potassium permanganate. Inactivation rates were
      found to be 1.4, 1.0 and 0.7 endotoxin units (EU)/mL h, for free chlorine,
      potassium permanganate and monochloramine, respectively. These rates are
      relatively slow given that contact times in drinking water distribution systems
      are typically less than 48 h. While small amounts of endotoxin may be removed by
      oxidation the observed removals are much less than those provided by physical
      removal processes. The significance of this finding is important for dialysis
      considerations but is as yet unclear with regard to inhalation, as the risk of
      inhaling sufficient quantities of endotoxin-containing aerosolized water droplets
      to adversely affect human health has not yet been adequately quantified.

PMID- 14568041
TI  - Mesophilic and thermophilic anaerobic digestion of primary and secondary sludge.
      Effect of pre-treatment at elevated temperature.
AB  - Anaerobic digestion is an appropriate technique for the treatment of sludge
      before final disposal and it is employed worldwide as the oldest and most
      important process for sludge stabilization. In general, mesophilic anaerobic
      digestion of sewage sludge is more widely used compared to thermophilic
      digestion. Furthermore, thermal pre-treatment is suitable for the improvement of
      stabilization, enhancement of dewatering of the sludge, reduction of the numbers
      of pathogens and could be realized at relatively low cost especially at low
      temperatures. The present study investigates (a) the differences between
      mesophilic and thermophilic anaerobic digestion of sludge and (b) the effect of
      the pre-treatment at 70 degrees C on mesophilic and thermophilic anaerobic
      digestion of primary and secondary sludge. The pre-treatment step showed very
      positive effect on the methane potential and production rate upon subsequent
      thermophilic digestion of primary sludge. The methane production rate was mostly
      influenced by the pre-treatment of secondary sludge followed by mesophilic and
      thermophilic digestion whereas the methane potential only was positively
      influenced when mesophilic digestion followed. Our results suggest that the
      selection of the pre-treatment duration as well as the temperature of the
      subsequent anaerobic step for sludge stabilization should depend on the ratio of
      primary to secondary sludge.

PMID- 14568042
TI  - Disinfection efficiency of peracetic acid, UV and ozone after enhanced primary
      treatment of municipal wastewater.
AB  - The City of Montreal Wastewater Treatment Plant uses enhanced physicochemical
      processes (ferric and/or alum coagulation) for suspended solids and phosphorus
      removal. The objective of this study was to assess the ability of peracetic acid
      (PAA), UV, or ozone to inactivate the indicator organisms fecal coliforms,
      Enterococci, MS-2 coliphage, or Clostridium perfringens in the effluent from this
      plant. PAA doses to reach the target fecal coliform level of 9000 CFU/100mL
      exceeded 6 mg/L; similar results were obtained for enterococci, and no
      inactivation of Clostridium perfringens was observed. However a 1-log reduction
      of MS-2 occurred at PAA doses of 1.5 mg/L and higher. It was expected that this
      effluent would have a high ozone demand, and would require relatively high UV
      fluences, because of relatively high effluent COD, iron and suspended solids
      concentrations, and low UV transmittance. This was confirmed herein. For UV, the
      inactivation curve for fecal coliforms showed the typical two-stage shape, with
      the target of 1000 CFU/100 mL (to account for photoreactivation) occurring in the
      asymptote zone at fluences >20 mJ/cm(2). In contrast, inactivation curves for MS
      2 and Clostridium perfringens were linear. Clostridium perfringens was the most
      resistant organism. For ozone, inactivation was already observed before any
      residuals could be measured. The transferred ozone doses to reach target fecal
      coliform levels ( approximately 2-log reduction) were 30-50 mg/L. MS-2 was less
      resistant, but Clostridium perfringens was more resistant than fecal coliforms.
      The different behaviour of the four indicator organisms studied, depending on the
      disinfectant, suggests that a single indicator organism might not be appropriate.
      The required dose of any of the disinfectants is unlikely to be economically
      viable, and upstream changes to the plant will be needed.

PMID- 14568043
TI  - Comparison of ammonia volatilisation rates in algae and duckweed-based waste
      stabilisation ponds treating domestic wastewater.
AB  - Quantification of ammonia volatilisation from wastewater stabilisation ponds is
      important in order to understand its significance for overall nitrogen removal in
      these widely applied low-cost treatment systems. Ammonia volatilisation rates
      were measured in pilot plant facilities consisting of one line of four algae
      based ponds in series and a parallel line of four ponds with a floating mat of
      duckweed (Lemna gibba). Ammonia volatilisation was assessed during a period of
      one and a half years. The method applied is accurate, convenient and is proposed
      for analysis of a wide range of gasses emitted from stabilisation ponds and
      possibly other aquatic systems. The ammonia volatilisation rates in algae-based
      ponds (ABPs) were higher than in duckweed-based ponds (DBPs). This can be
      explained by the lower values of NH(3) in DBPs due to shading and lower pH
      values, since the volatilisation rate highly correlated with free ammonia
      concentration (NH(3)) in pond water. The duckweed cover appeared not to provide a
      physical barrier for volatilisation of unionised ammonia, because whenever NH(3)
      concentrations were equal in ABP and DBP also the volatilisation rates were
      equal. Volatilisation was in the range of 7.2-37.4 mg-Nm(-2)d(-1) and 6.4 -31.5
      mg-Nm(-2)d(-1) in the ABPs and DBPs, respectively. Average influent and effluent
      ammonium nitrogen measurements showed that the ammonia volatilisation during the
      study period in any system did not exceed 1.5% of total ammonium nitrogen
      removal. Therefore this study confirmed results from simultaneous experimental
      work in our laboratory indicating that nitrification/denitrification, rather than
      ammonia volatilisation, is the most important mechanism for N removal in ABPs and
      DBPs.

PMID- 14568044
TI  - Temporal variability of dissolved P speciation in a eutrophic reservoir-
      implications for predicating algal growth.
AB  - Weak-anion exchange chromatography was used to explore the temporal variability
      in the speciation of dissolved P in the surface layer of a eutrophic reservoir.
      Authentic free ortho-P ion was the most common form of P on three of the five
      sampling occasions-including during a bloom of the green algae Botryococcus
      braunii indicating that the bloom was not P limited. Conversely, the absence of
      authentic ortho-P during a bloom of the dinoflagellate Ceratium hirundinella
      suggested the bloom was either P limited or co-limited. These observations were
      confirmed by algal-growth bioassay experiments.

PMID- 14568045
TI  - Rapid and economical indicator for evaluating arsenic removal with minimum
      aluminum residual during coagulation process.
AB  - Detection of various types of contaminants in water treatment plant by
      sophisticated analytical methods such as inductively coupled plasma/mass
      spectrometry and gas chromatography/mass spectrometry requires hours to days to
      provide the results. Because naturally occurring ultraviolet (UV) active
      compounds are commonly present in almost all source waters and can be rapidly
      monitored by UV absorbance at 260 nm (E260), the extent of correlation between
      the removal efficiency of E260 and the removal efficiency of As(V) with minimum
      soluble residual Al by coagulation process was investigated. Percentage removals
      for E260 were well correlated to those of As(V). When sufficient alum or
      polyaluminum chloride (PACl) was added for 60-65% removal of E260, 90-95% removal
      of As(V) was achieved with minimum soluble residual Al regardless of the initial
      level of turbidity, E260, and As(V). As E260 analysis is precisely available even
      by an unskilled plant operator in a few minutes, E260 removal efficiency appears
      to be the promising economical indicator for monitoring the effectiveness of the
      coagulation process for the removal of contaminants with minimum residual Al.

PMID- 14568046
TI  - Nylon fibers as supporting media in anaerobic hybrid reactors: it's effects on
      system's performance and microbial distribution.
AB  - The performances of three anaerobic hybrid reactors with various nylon fiber
      densities per packed bed volume (33, 22, and 11 kg/m(3) in R1, R2, and R3,
      respectively) as supporting media were evaluated through their ability to remove
      organic compounds in cassava starch wastewater. In addition, the distributions of
      non-methanogenic and methanogenic population in the reactors were investigated.
      During a 6-month operation, the organic loading rate was increased in stepwise
      from 0.5 to 4.0 kg COD/m3/day and the hydraulic retention time (HRT) shortened to
      5.4 days. The COD removal efficiency was more favorable in R1 (87%) and R2 (84%)
      than in R3 (70%). The total biomass in the reactors with greater nylon fiber
      densities was also higher and increased from 20.4 to 67.3 g VSS and to 57.5 g VSS
      in R1 and R2, respectively. When the HRT was further shortened to 3 days,
      however, the efficiency of both reactors demonstrated a declining trend and
      reached 74% in R1 and 61% in R2. The distribution of microbial populations
      involved in the reactors was determined using the Most Probable Number technique.
      The result showed the lowest number of methanogens in R3 which correlated well to
      its relatively low efficiency. The number of non-methanogens in all reactors was,
      nonetheless, comparable. By shortening the HRT to 3 days, the methanogenic
      population in R2 diminished in both attached and suspended biomass whereas a
      slight reduction was detected only in the attached biomass of R1.

PMID- 14568047
TI  - A standardisation of Ciona intestinalis (Chordata, Ascidiacea) embryo-larval
      bioassay for ecotoxicological studies.
AB  - A standardisation of the ascidian Ciona intestinalis embryo-larval bioassay for
      marine pollution assessment has been developed. The minimum percentage of
      embryogenesis success was established to assess the quality of the biological
      material used; minimum sample size and number of replicates per treatment were
      also estimated. The suitability of artificial and natural seawater for the
      incubation of ascidian embryos and larvae was compared, and the optimum
      conditions of temperature, salinity, pH, density of embryos in the vials and the
      sperm/egg ratio were investigated. On the basis of the 10th percentile of the
      distribution of larval abnormalities, we proposed a threshold of 50% normal
      larvae in the control in order to consider the test of acceptable biological
      quality. According to our results n=5 is a sufficiently high replication to
      detect 5% differences among treatment means with a power of P=90% and alpha=0.05,
      and a sampling size >/=222 allows a 95% confidence in the estimate with an error
      of 0.05. Egg density did not affect larval development within the range 1-20
      eggs/ml, and the optimum sperm/egg ratio which fertilise 100% of the eggs was
      3000-30,000 sperm/egg (i.e. 10(8)-10(7) sperm/ml). There were not significant
      differences between the two water types tested, and the optimum tolerance ranges
      were 18-23 degrees C temperature, 34-42 ppt salinity (42 ppt was the highest
      salinity tested), and 7.4-8.8 pH. The median effective concentration (EC(50)) of
      copper (Cu) causing a 50% reduction of normal hatched larvae was 54.2 microg/l
      (0.85 microM), which shows a sensitivity of this species similar to the commonly
      used bivalve and sea-urchin tests. The ascidian embryo-larval bioassay is an
      accurate, reliable, simple and rapid method that can be used in ecotoxicological
      studies.

PMID- 14568048
TI  - Partitioning variation of heavy metals in contaminated river sediment via
      bioleaching: effect of sulfur added to total solids ratio.
AB  - The aim of this study was to determine the effect of the ratio of sulfur added to
      total sediment solids (SA/TS) on the remobilization of heavy metals from
      contaminated river sediment by indigenous sulfur-oxidizing bacteria. Also, the
      difference in metal binding fractions before and after bioleaching was explored.
      It was found that sediment pH decreased at a significantly faster rate at higher
      SA/TS ratios (0.413 and 0.199) than at lower ones. Sulfate concentrations
      increased at a faster rate at these higher SA/TS ratios. At the lower SA/TS
      ratios, more acid must be produced and therefore it took more time for sulfur
      oxidizing bacteria to lower the sediment pH. Remobilization efficiency of total
      extractable Pb and Cr was significantly higher at higher SA/TS ratios. After
      bioleaching, Mn-oxides became a stronger binding pool, and the percentage of Pb
      and Zn bound to Mn-oxides and Cr and Cu bound to organic matter increased with
      the decrease of SA/TS. Different heavy metals showed different binding behavior
      at the various SA/TS ratios.

PMID- 14568049
TI  - Calcium accumulation on activated carbon deteriorates synthetic organic chemicals
      adsorption.
AB  - The accumulation of calcium on biological activated carbon (BAC) and their
      effects on adsorption of synthetic organic chemicals (SOCs) were studied using
      BAC, which have been operated for 5 (BAC5.0) and 3.5 (BAC3.5) years in a pilot
      scale water purification plant, and granular activated carbon (GAC) preloaded
      with fulvic acid and/or calcium. The major inorganic material accumulated on BAC
      was calcium. The amounts of calcium on BAC5.0 and BAC3.5 were 36.6 and 29.7 mg g(
      1), respectively. Seventy-one percent of calcium existed as calcium carbonate in
      both BACs. BAC5.0 had higher amount of accumulated calcium than BAC3.5 even
      though both BACs have already exhausted for NOM in the influent in 1-year
      operation, suggesting that calcium carbonate gradually accumulated on BAC even
      after the 3.5 years of operation. The isotherms of GAC preloaded with fulvic acid
      and/or calcium clearly indicated that the calcium accumulation on GAC reduced
      adsorption capacity for simazine. The conclusion also confirmed by significant
      recovery of adsorption capacity of both BACs by acid-washing to remove
      accumulated calcium from BACs. The difference of adsorption capacity between
      BAC3.5 and BAC5.0 was caused not only by the difference of adsorbed NOM but also
      the difference in the amount of accumulated calcium.

PMID- 14568050
TI  - Formation, modeling and validation of trihalomethanes (THM) in Malaysian drinking
      water: a case study in the districts of Tampin, Negeri Sembilan and Sabak Bernam,
      Selangor, Malaysia.
AB  - A modeling procedure that predicts trihalomethane (THM) formation from field
      sampling at the treatment plant and along its distribution system using Tampin
      district, Negeri Sembilan and Sabak Bernam district, Selangor as sources of data
      were studied and developed. Using Pearson method of correlation, the organic
      matter measured as TOC showed a positive correlation with formation of THM
      (r=0.380,P=0.0001 for Tampin and r=0.478,P=0.0001 for Sabak Bernam). Similar
      positive correlation was also obtained for pH in both districts with Tampin
      (r=0.362,P=0.0010) and Sabak Bernam (r=0.215,P=0.0010). Chlorine dosage was also
      found to have low correlation with formation of THM for the two districts with
      Tampin (r=0.233,P=0.0230) and Sabak Bernam (r=0.505,P=0.0001). Distance from
      treatment plant was found to have correlation with formation of THM for Tampin
      district with r=0.353 and P=0.0010. Other parameters such as turbidity, ammonia,
      temperature and residue chlorine were found to have no correlation with formation
      of THM. Linear and non-linear models were developed for these two districts. The
      results obtained were validated using three different sets of field data obtained
      from own source and district of Seremban (Pantai and Sg. Terip), Negeri Sembilan.
      Validation results indicated that there was significant difference in the
      predictive and determined values of THM when two sets of data from districts of
      Seremban were used with an exception of field data of Sg. Terip for non-linear
      model developed for district of Tampin. It was found that a non-linear model is
      slightly better than linear model in terms of percentage prediction errors. The
      models developed were site specific and the predictive capabilities in the
      distribution systems vary with different environmental conditions.

PMID- 14568051
TI  - Evolution of antibiotic occurrence in a river through pristine, urban and
      agricultural landscapes.
AB  - A river along the semi-arid Front Range of Colorado was monitored for antibiotics
      including five tetracycline and six sulfonamide compounds. Existing analytical
      methods were adapted to measure these compounds in a surface water matrix at
      environmentally relevant concentrations (0.05 microg/L). Natural organic matter
      present in surface waters was confirmed to significantly impact the low-level
      analysis of tetracyclines (TCs) necessitating the use of standard addition
      quantification techniques. Five sites along the Cache la Poudre River were
      monitored for antibiotics encompassing pristine areas without anthropogenic
      influence, urban areas impacted by wastewater discharges and agricultural areas
      susceptible to non-point source contaminant runoff. The only site at which no
      antibiotics were detected was the pristine site in the mountains before the river
      had encountered urban or agricultural landscapes. By the time the river had
      exited the urban area, 6 of the 11 antibiotic compounds that were monitored were
      found in the samples. At Site 5, which had both urban and agricultural influences
      all five of the TCs monitored were detected indicating both urban and
      agricultural influences. The concentration of TCs at Site 5 ranged from 0.08 to
      0.30 microg/L.

PMID- 14568052
TI  - DEHP enrichment in the surface microlayer of a small eutrophic lake.
AB  - Investigation of di-2-ethylhexyl phthalate (DEHP) in the surface microlayer (SM)
      and subsurface water (SSW) of a small eutrophic lake was carried out from April
      to June 2002. Results obtained from the field samples showed that tens to several
      hundred mug/L of DEHP was found in each sample of SM and SSW, indicating that the
      lake has been polluted by DEHP. Linear regression analysis showed that
      concentrations of DEHP were more strongly correlated with sampling temperature
      than with chlorophyll a concentrations. Correlation between DEHP concentrations
      and total phosphor concentrations was also obtained. Enrichment factors (EFs) of
      DEHP in the SM comparing with the corresponding SSW were ranging over 0.85-2.12
      with an average of 1.35. DEHP EFs were significantly related to both enrichment
      of chlorophyll a in the SM and sampling temperature.

PMID- 14568053
TI  - Aqueous chemistry and interactive effects on non-ionic surfactant and
      pentachlorophenol sorption to soil.
AB  - Non-ionic surfactant addition was investigated as a method to remediate
      pentachlorophenol (PCP) contaminated soil. The goal was to quantify surfactant
      (Tergitol NP-10 (TNP10)) and PCP sorption to soil and their interactive effects
      under varying pH, ionic strength, and soil conditions. Up to 16,700 mg/kg of
      TNP10 partitioned to soil, with increasing sorption far above the critical
      micelle concentration (CMC) and with greater amounts of PCP present.
      Approximately 40-45 times more TNP10 and 20-30 times more PCP sorbed to the finer
      soil with higher organic matter content. Aqueous TNP10 concentrations well above
      the CMC (>/=5500 mg/L) were required to enhance PCP desorption from the soil. As
      pH increased by 0.5-0.85 units, TNP10 sorption decreased by 14-25% and PCP
      sorption as measured by the log of the equilibrium partition coefficient
      decreased by 1-1.5. A lower ionic strength of 0.03 versus 0.112 M increased PCP
      desorption from contaminated soil by 5-17% in the presence of TNP10. This work is
      relevant to designing ex situ soil washing or surfactant-aided PCP remediation.

PMID- 14568054
TI  - Application of the mass transfer model for describing nonequilibrium transport of
      HOCs through natural geosorbents.
AB  - Column experiments of nonsorbing and sorbing solutes were conducted in sandy
      aquifer material. Results of the column experiments were analyzed using a
      numerical nonequilibrium mass transfer model (designated as dispersed flow, film
      and particle diffusion model, DF-FPDM), an equilibrium advection-dispersion model
      (designated as dispersed flow, local equilibrium model, DF-LEM) as well as a
      nonequilibrium two region (mobile-immobile) advection-diffusion model (designated
      as homogeneous solid diffusion model, HSDM). Results of the analyses revealed
      that in all experiments the experimental BTCs are much better predicted by the DF
      FPDM than by DF-LEM and HSDM. The relative influence of different processes (film
      diffusion, intraparticle diffusion and dispersion) can be identified by
      dimensionless mass transfer parameters N(F), N(S) and N(D). Their plausibility
      can be compared with the well-known advection-dispersion-based equilibrium model.
      In general, spreading and asymmetry of sorbing solute BTCs can be explained with
      the DF-LEM and HSDM, but the identification of different processes and their
      influence on the total transport processes can only be ascertained with a model
      like DF-FPDM.

PMID- 14568055
TI  - Adhesion of in situ precipitated calcium carbonate in the presence and absence of
      magnetic field in quiescent conditions on different solid surfaces.
AB  - Deposition of in situ precipitated calcium carbonate from Na(2)CO(3) and CaCl2
      solutions on different substrates, i.e. stainless steel, copper, aluminium, and
      glass, was investigated at different temperatures, 20 degrees C, 40 degrees C, 60
      degrees C and 80 degrees C, both in the absence and presence of S-S 0.1T magnetic
      field (MF). It was found that in quiescent conditions during 2h the amounts
      deposited firmly on the surfaces decreased with increasing temperature. If MF was
      present the deposition was reduced at all temperatures, and depended on the
      nature of the substrate. The largest MF effect was found on glass at 60 degrees
      C, which amounted 50% reduction of the deposit. However, at 80 degrees C no
      deposition was found in the presence of MF on aluminium surface. At this
      temperature the reproducibility of the experiments was poor, and an additional
      effect due to the metal surface corrosion (especially that of aluminium and
      copper) may be thought in alkaline environment of the experiments (pH ca. 10).
      Based on optical microscope photographs, it was concluded that the amounts of
      crystallographic forms of CaCO3 depended on the nature of substrate on which the
      precipitation and then the adhesion took place. To some extent the ratios of
      CaCO3 forms precipitated were different in the bulk phase than on the substrate
      surfaces at the same temperature, and this conclusion was based on the X-ray
      diffractograms. Some possible mechanisms causing MF effects are discussed.

PMID- 14568056
TI  - Reduction of ClO2 demand by ClO2 oxidation and subsequent GAC filtration.
AB  - The effective removal of soluble natural organic matter (NOM) during water
      treatment can significantly decrease the ClO(2) demand of processed water. This
      can be achieved through the oxidation and/or the removal of NOM. The purpose of
      the study was to examine the influence of ClO(2) oxidation and subsequent GAC
      filtration on the final ClO(2) demand of treated water. The study showed the
      ClO(2) demand to be strongly correlated with the abundance of high molecular
      fractions of NOM in treated water. As it was shown, this part of NOM was
      effectively removed during the GAC filtration. Moreover, the pre-treatment of
      water with ClO(2) considerably increased the total capacity of GAC filters for
      organic and inorganic (i.e. chlorites) oxidation by-products. Therefore, the
      oxidation of NOM molecules in conjunction with a very efficient GAC filtration
      can be successfully employed to control the abundance of high molecular NOM
      components, and thus the ClO(2) demand of finished water.

PMID- 14568057
TI  - Detection of somatic phages, infectious enteroviruses and enterovirus genomes as
      indicators of human enteric viral pollution in surface water.
AB  - In the present study, we aimed to determine whether the concentrations of somatic
      coliphages, infectious enteroviruses or the detection of enterovirus genomes were
      associated with the detection of human pathogenic viruses in surface water. Four
      French rivers were sampled monthly or semimonthly for the quantitative detection
      of somatic coliphages, infectious enteroviruses and the qualitative RT-PCR
      detection of enterovirus, hepatitis A virus, Norwalk I viruses, Norwalk II
      viruses, astrovirus and rotavirus genomes over 12 months. All the 68 water
      samples tested were positive for the quantitative detection of somatic coliphages
      (range of concentrations: 4 x 10(2) to 1.6 x10(5) FUl(-1)). Infectious
      enteroviruses were isolated by a cell culture system in only two (3%) of the 68
      concentrated water samples tested, whereas enterovirus genomes were detectable in
      60 (88%) of the same samples. A positive RT-PCR detection of the genome of
      hepatitis A virus, Norwalk-like virus genogroup II, astrovirus, rotavirus and
      Norwalk-like virus genogroup I was demonstrated, respectively, in 1.5% (1/68),
      1.5% (1/68), 3% (2/68), 0% and 0% of the 68 concentrated water samples tested.
      All of these four water samples were positive for the detection of enterovirus
      genomes, whereas only one of them was positive for the isolation of enteroviruses
      on cell culture. Moreover, the genomic detection of human pathogenic viruses
      appeared not to be statistically associated with the concentration levels of
      somatic coliphages in the 68 concentrated water samples tested (Wilcoxon rank
      test; P=0.14). Taken together, our findings indicate that the quantitative
      detection of somatic coliphages and the isolation of enteroviruses on cell
      culture are not suitable parameters for the control of the viral contamination in
      surface water, whereas the detection of enterovirus genomes may be useful for
      predicting the presence of waterborne viruses.

PMID- 14568058
TI  - Improvement of organics removal by bio-ceramic filtration of raw water with
      addition of phosphorus.
AB  - The purpose of this study was to investigate the effect of phosphorus addition on
      biological pretreatment of raw water. Experiments were conducted in pilot-scale
      bio-ceramic filters with raw water from a reservoir located in Beijing, China.
      The results demonstrated that phosphorus was the limiting nutrient for bacterial
      growth in the raw water investigated in this study. The measured values of
      bacterial regrowth potential (BRP) and biodegradable dissolved organic carbon
      (BDOC) of the raw water increased by 50-65% and 30-40% with addition of 50 microg
      of PO4(3-)-PL(-1), respectively. Addition of 25 microg of PO4(3-)-PL(-1) to the
      influent of bio-ceramic filter enhanced the percent removal of organics by 4.6,
      5.7 and 15 percentage points in terms of COD(Mn), TOC and BDOC, respectively.
      Biomass in terms of phospholipid content increased by 13-22% and oxygen uptake
      rate (OUR) increased by 35-45%. The ratio of C:P for bacteria growth was 100:1.6
      for the raw water used in this study. Since change of phosphorus concentrations
      can influence the performance of biological pretreatment and the biological
      stability of drinking water, this study is of substantial significance for
      waterworks in China. The role of phosphorus in biological processes of drinking
      water should deserve more attention.

PMID- 14568059
TI  - Modeling leaching of viruses by the Monte Carlo method.
AB  - A predictive screening model was developed for fate and transport of viruses in
      the unsaturated zone by applying the final value theorem of Laplace
      transformation to previously developed governing equations. A database of input
      parameters allowed Monte Carlo analysis with the model. The resulting kernel
      densities of predicted attenuation during percolation indicated very small, but
      finite probabilities of failure for all homogeneous USDA classified soils to
      attenuate reovirus 3 by 99.99% in one-half meter of gravity drainage. The
      logarithm of saturated hydraulic conductivity and water to air-water interface
      mass transfer coefficient affected virus fate and transport about 3 times more
      than any other parameter, including the logarithm of inactivation rate of
      suspended viruses. Model results suggest extreme infiltration events may play a
      predominant role in leaching of viruses in soils, since such events could impact
      hydraulic conductivity. The air-water interface also appears to play a
      predominating role in virus transport and fate. Although predictive modeling may
      provide insight into actual attenuation of viruses, hydrogeologic sensitivity
      assessments for the unsaturated zone should include a sampling program.

PMID- 14568060
TI  - Impact of hydrogen peroxide on nitrite formation during UV disinfection.
AB  - One concern with UV disinfection of water is the production of nitrite when
      polychromatic UV sources are utilized. Based on previous work, it was
      hypothesized that a small addition of hydrogen peroxide (H(2)O(2)) may be useful
      in controlling nitrite during UV disinfection. However, it was found that
      H(2)O(2) addition (5 or 10mg/L) during polychromatic UV irradiation of drinking
      water at doses used for disinfection significantly increases the levels of
      nitrite produced relative to solutions without H(2)O(2). Enhancement rates ranged
      from approximately 15% to 40% depending upon pH and H(2)O(2) concentration; the
      relative increase in the NO(2)(-) yield was greater at pH 6.5 than at pH 8.3. The
      observed effects are tentatively ascribed to a combination of enhanced superoxide
      production and increased hydroxyl radical scavenging when H(2)O(2) is added.
      These results indicate that H(2)O(2) cannot be used to control nitrite production
      during UV disinfection and that enhanced nitrite formation will occur if H(2)O(2)
      is added during UV water treatment to achieve advanced oxidation of contaminants.

PMID- 14568061
TI  - Synergistic inactivation of Cryptosporidium parvum using ozone followed by free
      chlorine in natural water.
AB  - The synergistic effect of sequential exposure to ozone followed by free chlorine
      on inactivation of Cryptosporidium parvum oocysts suspended in natural waters was
      studied in bench-scale batch reactors. Animal infectivity using neonatal CD-1
      mice was used to measure oocyst inactivation. The synergistic effect measured in
      two alkaline (pH 8.1) natural waters was statistically significant but was
      considerably smaller than previously reported in buffered de-ionized water at pH
      6.0. Temperature, ozone primary treatment level, and water type did not have
      measurable impacts on the synergistic effect. Efforts to increase the synergistic
      effect by reducing the pH from 8 to 6 by acid addition were unsuccessful. In the
      two low alkalinity (pH 6.0) natural waters tested, the measured synergistic
      effect was greater than in the alkaline waters, but was still less than that
      measured previously in buffered de-ionized water. It was concluded that the
      synergistic effect reduction in the natural waters tested was due in part to
      alkalinity and in part to other unidentified water quality characteristics.
      Sequential treatment with ozone followed by free chlorine may only be a feasible
      strategy for achieving synergistic C. parvum inactivation credit for water
      treatment facilities with natural waters having a low pH (near 6.0).

PMID- 14568062
TI  - Degradation of microcystin in sediments at oxic and anoxic, denitrifying
      conditions.
AB  - The potent toxin microcystin is frequently released during cyanobacterial blooms
      in eutrophic waters and may impose a risk to human health, when surface water is
      used for drinking water. For removal of microcystin in surface waters,
      infiltration through sediment is commonly used. In the present study,
      mineralization of 14C-labelled microcystin (accumulation of 14CO(2)) and
      concentration changes (protein phosphatase inhibition assay) demonstrated that
      indigenous microorganisms in the sediment of a water recharge facility were
      capable of degrading microcystin. At oxic or microaerophilic (<2% O(2))
      conditions, microcystin added to sediment slurries at 70 microg l(-1) was reduced
      to <20 microg l(-1) in 1-2 weeks, and less than 3 microg l(-1) after 7 weeks. At
      anoxic conditions (<0.3% O(2)) and with addition of nitrate, the degradation was
      significantly stimulated, reducing microcystin from 100 to <20 microg l(-1)
      within 1 day. The simultaneous production of N(2)O in the samples suggests that
      the microcystin degradation was coupled to dissimilative nitrate reduction
      (denitrification). Since aquifers and sediments beneath drinking water reservoirs
      often are anoxic, nitrate respiration may be an important process in removal and
      detoxification of microcystin.

PMID- 14568063
TI  - Nutrient level, microbial activity, and alachlor transformation in aerobic
      aquatic systems.
AB  - Alachlor (2-chloro-N-(2,6-diethylphenyl)-N-(methoxymethyl)acetamide) is a
      moderately toxic herbicide that is frequently found in agriculturally impacted
      surface waters. To assess primary mechanism(s) that affect its fate in aquatic
      systems, two field experiments were performed using large mesocosms (n=39) and
      smaller microcosms with and without microbial inhibitors (n=16). The mesocosm
      experiment tested the effect of fertility conditions on alachlor fate, assessing
      alachlor disappearance over time under oligotrophic (total phosphorus (TP) <12
      microg/L) through hypereutrophic (TP>80 microg/L) water conditions. Whereas, the
      microcosm experiment assessed alachlor fate in the presence of microbial
      inhibitors that selectively blocked eubacterial (chloroamphenicol, streptomycin,
      and penicillin combined), eukaryotic (cycloheximide), and universal (all
      inhibitors) microbial activity. First-order alachlor transformation rate
      coefficients ranged from 0.006 to 0.042 day(-1) when microbial inhibitors were
      not present (half-lives from 16 to 122 days) with the highest rates occurring in
      hypereutrophic waters. Statistics indicated that mean TP, and universal and
      eubacterial small sub-unit rRNA level most closely correlated with transformation
      rate. Further, the inhibitor study indicated that alachlor transformation was
      biotic (>90%), but that high transformation rates only occurred when eubacterial
      and eukaryotic domains were both metabolically active. Our results confirm that
      alachlor transformation is primarily biotic; however, efficient biotransformation
      only occurs when both major microbial domains in aerobic systems are active.

PMID- 14568064
TI  - Chemical modification of chitosan and equilibrium study for mercury ion removal.
AB  - To increase the uptake capacity of mercury ions, several chemical modifications
      of chitosan beads which are cross-linked with glutaraldehyde were performed.
      Among them, aminated chitosan bead prepared through chemical reaction with
      ethylenediamine had a high uptake capacity of about 2.3 mmol g(-1) dry mass at pH
      7. The increased number of amine groups was confirmed by IR analysis and
      measuring the saturation capacities for adsorption of HCl. The surface condition
      and existence of mercury ions on the beads was confirmed by the environmental
      scanning electron microscope and energy dispersive X-ray spectroscopy
      instrumental analyses. The beads showed the characteristic of competitive
      sorption between mercury and hydrogen ions and it was successfully modelled by an
      equilibrium model.

PMID- 14568065
TI  - Membrane bioreactor for the drinking water treatment of polluted surface water
      supplies.
AB  - A laboratory membrane bioreactor (MBR) using a submerged polyethylene hollow
      fibre membrane module with a pore size of 0.4 microm and a total surface area of
      0.2 m2 was used for treating a raw water supply slightly polluted by domestic
      sewage. The feeding influent had a total organic carbon (TOC) level of 3-5 mg/L
      and an ammonia nitrogen (NH(3)-N) concentration of 3-4 mg/L. The MBR ran
      continuously for more than 500 days, with a hydraulic retention time (HRT) as
      short as 1h or less. Sufficient organic degradation and complete nitrification
      were achieved in the MBR effluent, which normally had a TOC of less than 2 mg/L
      and a NH(3)-N of lower than 0.2 mg/L. The process was also highly effective for
      eliminating conventional water impurities, as demonstrated by decreases in
      turbidity from 4.50+/-1.11 to 0.08+/-0.03 NTU, in total coliforms from 10(5)/mL
      to less than 5/mL and in UV(254) absorbance from 0.098+/-0.019 to 0.036+/-0.007
      cm(-1). With the MBR treatment, the 3-day trihalomethane formation potential
      (THMFP) was significantly reduced from 239.5+/-43.8 to 60.4+/-23.1 microg/L. The
      initial chlorine demand for disinfection decreased from 22.3+/-5.1 to 0.5+/-0.
      1mg/L. The biostability of the effluent improved considerably as the assimilable
      organic carbon (AOC) decreased from 134.5+/-52.7 to 25.3+/-19.9 microg/L. All of
      these water quality parameters show the superior quality of the MBR-treated
      water, which was comparable to or even better than the local tap water. Molecular
      size distribution analysis and the hydrophobic characterisation of the MBR
      effluent, in comparison to the filtered liquor from the bioreactor, suggest that
      the MBR had an enhanced filtration mechanism. A sludge layer on the membrane
      surface could have functioned as an additional barrier to the passage of typical
      THM precursors, such as large organic molecules and hydrophobic compounds. These
      results indicate that the MBR with a short HRT could be developed as an effective
      biological water treatment process to address the urgent need of many developing
      countries that are plagued by the serious contamination of surface water
      resources.

PMID- 14568066
TI  - A multi-component statistic analysis for the influence of sediment/soil
      composition on the sorption of a nonionic surfactant (Triton X-100) onto natural
      sediments/soils.
AB  - The contents of soil/sediment organic carbon and clay minerals (i.e.
      montmorillonite, kaolinite, illite, gibbsite and 1.4 nm minerals) for 21 natural
      soil/sediment samples and the sorption of Triton X-100 on these samples were
      determined. A multi-component statistic analysis was employed to investigate the
      importance of soil/sediment organic matters and clay minerals on their sorption
      of Triton X-100. The sorption power of soil/sediment composition for Triton X-100
      conforms to an order of montmorillonite>organic carbon>illite>1.4 nm minerals
      (vermiculite+chlorite+1.4 nm intergrade mineral)>>kaolinite. The sorption of
      Triton X-100 on a montmorillonite, a kaolinite and a humic acid were also
      investigated and consistent with the result of multi-component statistic
      analysis. It is clear that the sorption of Triton X-100 on soils or sediments is
      the combined contribution of soil/sediment organic matters and clay minerals,
      which depended on both the contents of soil/sediment organic matters and the
      types and contents of clay minerals. The important influence of illite on the
      sorption of nonionic surfactants onto soils/sediments is suggested and
      demonstrated in this paper. Surfactants for aquifer remediation application may
      be more efficient for the contaminated soils/sediments that contain little clay
      minerals with 2:1 structure because of the less sorption of nonionic surfactants
      on these soils/sediments.

PMID- 14568067
TI  - Treatability of organic fractions derived from secondary effluent by reverse
      osmosis membrane.
AB  - Dissolved organic matters (DOMs) from two batches of secondary effluent collected
      from a local water reclamation plant were fractionated using column
      chromatographic method with non-ionic resins XAD-8, AG MP-50 and IRA-96. Seven
      isolated fractions were obtained from the fractionation study and these fractions
      were quantified using DOC, UV(254) and SUVA values. The fractionation study
      revealed that the secondary effluent samples comprised about 47.3-60.6% of
      hydrophobic and 39.4-52.7% of hydrophilic solutes. The treatability of each
      isolated fraction was investigated by subjecting each fraction to reverse osmosis
      (RO) treatment individually. It was noted that RO process could achieve high DOC
      rejections for acid and neutral fractions (ranging from 80% to 98% removal)
      probably due to the negative charge of RO membrane. The results obtained also
      indicated that hydrophobicity of DOMs is significant in determining treatability
      of organic species by RO process. The performance of RO in terms of DOC rejection
      of un-fractionated secondary effluent was also investigated to assess possible
      effects of interactions among organic fractions on their treatability by RO
      process. It was noted that DOC rejection associated with the un-fractionated
      secondary effluent was generally higher (ranging from 2% to 45%) than the
      corresponding rejection obtained from each individual fraction isolated from the
      secondary effluent. This finding suggested there is a beneficial interaction
      among the fractions that in turn has contributed towards a better overall DOC
      rejection performance by RO treatment.

PMID- 14568068
TI  - Development of a protocol for the isolation of Listeria monocytogenes from
      sludge.
AB  - Given the high level of background flora in sludge, methods for detecting
      Listeria monocytogenes are not well established. In this study, two critical
      parameters for the detection of L. monocytogenes were evaluated: the
      concentration of Listeria sp. in a modified Fraser broth (first stage of the
      method) and the proportion of L. monocytogenes on Palcam agar (second stage of
      the method). Concentrations of Listeria sp. estimated in 118 modified Fraser
      enrichment broths inoculated with four types of sludge, reached 10(4) bacteria
      per mL for 83% of the positive enrichment broths. Proportion of L. monocytogenes
      on Palcam agar, which was estimated by transferring all characteristic colonies
      of Listeria sp. onto Rapid'L Mono agar, was highly variable regardless of the
      type of sludge. According to these results, we proposed a protocol that consisted
      of an enrichment in modified Fraser broth for 48 h at 37 degrees C, followed by
      plating 0.1 mL of appropriate dilutions of broth onto Palcam agar. After an
      incubation of 48 h at 37 degrees C, a systematic identification of characteristic
      colonies of Listeria sp. on Rapid'L Mono agar allowed to enhance the detection of
      Listeria monocytogenes.

PMID- 14568069
TI  - myo-Inositol-1,2,3,4,5,6-hexakisphosphate.
AB  - myo-Inositol-1,2,3,4,5,6-hexakisphosphate (Ins P(6)) was first described as an
      abundant form of phosphorus in plant seeds and other plant tissues and dubbed
      "phytic acid". Subsequently it was found to be a common constituent in eukaryotic
      cells, its metabolism a basic component of cellular housekeeping. In addition to
      phosphate, myo-inositol (Ins) and mineral storage and retrieval in plant organs
      and tissues, other roles for Ins P(6) include service as a major metabolic pool
      in Ins phosphate and pyrophosphate pathways involved in signaling and regulation;
      possibly as an effector or ligand in these processes; as a form of energy
      currency and in ATP regeneration; in RNA export and DNA repair; and as an anti
      oxidant. The relatively recent demonstration that pyrophosphate-containing
      derivatives of Ins P(6) can function as phosphate donors in the regeneration of
      ATP is reminiscent of the proposal, made four decades ago in studies of seed
      development, that Ins P(6) itself may serve in this function. Studies of Ins P(6)
      in non-plant systems rarely include the consideration that this compound might
      represent a significant fraction of cellular P; cellular phosphate nutrition has
      been viewed as either not interesting or of little importance. However, there may
      be few fundamental differences among diverse eukaryotes in both the metabolic
      pathways involving Ins P(6) and the spectrum of possible roles for it and its
      metabolites.

PMID- 14568070
TI  - Covalent binding of chloroacetamide herbicides to the active site cysteine of
      plant type III polyketide synthases.
AB  - Chloroacetamide herbicides inhibit very-long-chain fatty acid elongase, and it
      has been suggested that covalent binding to the active site cysteine of the
      condensing enzyme is responsible [Pest Manage Sci 56 (2000), 497], but direct
      evidence was not available. The proposal implied that other condensing enzymes
      might also be targets, and therefore we have investigated four purified
      recombinant type III plant polyketide synthases. Chalcone synthase (CHS) revealed
      a high sensitivity to the chloroacetamide metazachlor, with 50% inhibition after
      a 10 min pre-incubation with 1-2 molecules per enzyme subunit, and the
      inactivation was irreversible. Stilbene synthase (STS) inactivation required 20
      fold higher amounts, and 4-coumaroyltriacetic acid synthase and pyrone synthase
      revealed no response at the highest metazachlor concentrations tested. A similar
      spectrum of differential responses was detected with other herbicides that also
      inhibit fatty acid elongase (metolachlor and cafenstrole). The data indicate that
      type III polyketide synthases are potential targets of these herbicides, but each
      combination has to be investigated individually. The interaction of metazachlor
      with CHS was investigated by mass spectrometric peptide mapping, after incubation
      of the enzymes with the herbicides followed by tryptic digestion. A
      characteristic mass shift and MS/MS sequencing of the respective peptide showed
      that metazachlor was covalently bound to the cysteine of the active site, and the
      same was found with STS. This is the first direct evidence that the active site
      cysteine in condensing enzymes is the primary common target of these herbicides.

PMID- 14568071
TI  - Plastoquinones are effectively reduced by ferredoxin:NADP+ oxidoreductase in the
      presence of sodium cholate micelles. Significance for cyclic electron transport
      and chlororespiration.
AB  - The effect of sodium cholate and other detergents (Triton X-100, sodium dodecyl
      sulphate, octyl glucoside, myristyltrimethylammonium bromide) on the reduction of
      plastoquinones (PQ) with a different length of the side-chain by spinach
      ferredoxin:NADP(+) oxidoreductase (FNR) in the presence of NADPH has been
      studied. Both NADPH oxidation and oxygen uptake due to plastosemiquinone
      autoxidation were highly stimulated only in the presence of sodium cholate among
      the used detergents. Sodium cholate at the concentration of 20 mM was found to be
      the most effective on both PQ-4 and PQ-9-mediated oxygen uptake. The FNR
      dependent reduction of plastoquinones incorporated into sodium cholate micelles
      was stimulated by spinach ferredoxin but inhibited by Mg(2+) ions. It was
      concluded that the structure of sodium cholate micelles facilitates contact of
      plastoquinone molecules with the enzyme and creates favourable conditions for the
      reaction similar to those found in thylakoid membranes for PQ-9 reduction. The
      obtained results were discussed in terms of the function of FNR as a
      ferredoxin:plastoquinone reductase both in cyclic electron transport and
      chlororespiration.

PMID- 14568072
TI  - Hofmannolin, a cyanopeptolin from Scytonema hofmanni PCC 7110.
AB  - Two depsipeptide metabolites, scyptolin A and B, were reported recently from the
      axenically grown terrestrial cyanobacterium Scytonema hofmanni PCC 7110. A
      related, novel depsipeptide was isolated from this Scytonema and designated
      hofmannolin. The amino acid analysis in context with infrared, mass and 1H/13C
      NMR spectroscopies revealed a cyclic depsipeptide structure of M(r) 1073
      belonging to the class of cyanopeptolins. Two peculiar features distinguish
      hofmannolin from other cyanopeptolins: O-methylated tyrosine forms the sixth
      moiety from the amino terminus, and the N-terminus is blocked by 2-hydroxy-3
      methyl-valeric acid, a residue that has not yet been reported as a component in
      other cyanopeptolins. Preliminary assays of peptidase inhibitory and
      antimicrobial activities suggested negligible bioactivities for hofmannolin.

PMID- 14568073
TI  - Cloning and regiospecificity studies of two flavonoid glucosyltransferases from
      Allium cepa.
AB  - Two UDP-glucose-dependent flavonoid glucosyltransferases (EC 2.4.1.-) isolated
      from the epidermal layer of yellow onion (Allium cepa) were functionally
      expressed in Escherichia coli and their substrate specificity investigated. The
      two enzymes exhibited different substrate- and regio-specificity profiles. A.
      cepa UGT73G1 used a wide range of different flavonoid substrates including
      flavonoids not naturally occurring in onion. Regiospecificity was indicated for
      hydroxyl-groups of the C-3, C-7 and C-4' positions of the flavan backbone
      structure to yield flavonoid mono- and diglucosides. In contrast, A. cepa UGT73J1
      showed activity only with the flavonoid mono-glucoside isoquercitrin and the
      isoflavone aglycone genistein, with regiospecificity for the C-7 position. The
      regiospecificity for both enzymes included positions that are glucosylated in
      flavonoids of onion bulbs, indicating their involvement in flavonoid biosynthesis
      in A. cepa.

PMID- 14568074
TI  - Natural variation for seed oil composition in Arabidopsis thaliana.
AB  - The biochemical pathways involved in the biosynthesis and accumulation of storage
      lipids in seeds have been extensively studied. However, the regulatory mechanisms
      of those pathways, their environmental interactions and the ecological
      implications of variation are poorly understood. We have initiated a new
      approach: the analysis of natural variation in Arabidopsis thaliana. Three
      hundred and sixty accessions were surveyed for content of oil, very long chain
      fatty acids (VLCFAs) and polyunsaturated fatty acids (PUFAs) in their seeds. The
      results revealed extensive natural variation. A core set of accessions, the seeds
      of which reproducibly contain extreme amounts of oil, VLCFAs and PUFAs have been
      identified. Reproducible oil content ranged from 34.6 to 46.0% of seed dry
      weight. VLCFA content ranged from 13.0 to 21.2% of total fatty acids. PUFA
      content, ranged from 53.3 to 66.1% of total fatty acids. Interactions were also
      identified for PUFA and VLCFA content of seeds with vernalisation of plants.
      Mapping of the regions of the genome involved in controlling the traits was
      conducted in an F(2) population and indicated that natural variation at the loci
      FAE1 and FAD3 might be involved in the regulation of VLCFA and PUFA content,
      respectively. A set of accessions, which capture a broad range of the natural
      variation for these traits available in A. thaliana, has been selected to form a
      core set which can be used to further dissect the genetics of the regulation of
      seed lipid traits and to identify the genes involved.

PMID- 14568075
TI  - More chemistry of the thaxtomin phytotoxins.
AB  - Chemical and biochemical studies indicated the possible involvement of N
      acetyltryptophan and 4-nitrotryptophan as intermediates in biosynthesis of the
      thaxtomin phytotoxins. A search for other potential pathways indirectly resulted
      in the identification of three unusual thaxtomin analogues derived from the o
      thaxtomin A isomer. Investigations to resolve the identity of a previously
      described thaxtomin A di-glucoside were not supportive of the proposed structure.

PMID- 14568076
TI  - An in silico assessment of gene function and organization of the phenylpropanoid
      pathway metabolic networks in Arabidopsis thaliana and limitations thereof.
AB  - The Arabidopsis genome sequencing in 2000 gave to science the first blueprint of
      a vascular plant. Its successful completion also prompted the US National Science
      Foundation to launch the Arabidopsis 2010 initiative, the goal of which is to
      identify the function of each gene by 2010. In this study, an exhaustive analysis
      of The Institute for Genomic Research (TIGR) and The Arabidopsis Information
      Resource (TAIR) databases, together with all currently compiled EST sequence
      data, was carried out in order to determine to what extent the various metabolic
      networks from phenylalanine ammonia lyase (PAL) to the monolignols were organized
      and/or could be predicted. In these databases, there are some 65 genes which have
      been annotated as encoding putative enzymatic steps in monolignol biosynthesis,
      although many of them have only very low homology to monolignol pathway genes of
      known function in other plant systems. Our detailed analysis revealed that
      presently only 13 genes (two PALs, a cinnamate-4-hydroxylase, a p-coumarate-3
      hydroxylase, a ferulate-5-hydroxylase, three 4-coumarate-CoA ligases, a cinnamic
      acid O-methyl transferase, two cinnamoyl-CoA reductases) and two cinnamyl alcohol
      dehydrogenases can be classified as having a bona fide (definitive) function; the
      remaining 52 genes currently have undetermined physiological roles. The EST
      database entries for this particular set of genes also provided little new
      insight into how the monolignol pathway was organized in the different tissues
      and organs, this being perhaps a consequence of both limitations in how tissue
      samples were collected and in the incomplete nature of the EST collections. This
      analysis thus underscores the fact that even with genomic sequencing, presumed to
      provide the entire suite of putative genes in the monolignol-forming pathway, a
      very large effort needs to be conducted to establish actual catalytic roles
      (including enzyme versatility), as well as the physiological function(s) for each
      member of the (multi)gene families present and the metabolic networks that are
      operative. Additionally, one key to identifying physiological functions for many
      of these (and other) unknown genes, and their corresponding metabolic networks,
      awaits the development of technologies to comprehensively study molecular
      processes at the single cell level in particular tissues and organs, in order to
      establish the actual metabolic context.

PMID- 14568077
TI  - The absolute configuration of prunioside A from Spiraea prunifolia and biological
      activities of related compounds.
AB  - The stereochemistry of prunioside A isolated from Spiraea prunifolia was
      determined by chemical transformations and NMR spectral data analysis. The
      configurations at C-5 and C-6 were determined to be 5S and 6R by application of
      the modified Mosher's method, CD analysis, and 13C NMR spectroscopic data
      analysis of an acetonide derivative. Other compounds related to prunioside A have
      inhibitory effects on the synthesis of nitric oxide in LPS-stimulated macrophage
      like RAW 264.7 cells.

PMID- 14568078
TI  - Antifeedant neo-clerodanes from Teucrium tomentosum Heyne. (Labiatae).
AB  - From the acetone extract of Teucrium tomentosum, a new antifeedant neo-clerodane
      diterpenoid teuctosin (1) was isolated along with teuflin (2), teucrin-H(2) (3),
      6beta-hydroxyteuscordin (4), 6beta-acetylteuscordin (5) and montanin-D (6). The
      structure of the new compound was elucidated comprehensively using 1D and 2D NMR
      methods and confirmed by X-ray crystallography. All the compounds showed
      effective antifeedancy against Plutella xylostella and Spodoptera litura at 10
      mug/cm(2) of leaf area.

PMID- 14568079
TI  - Diterpenes from Alomia myriadenia (Asteraceae) with cytotoxic and trypanocidal
      activity.
AB  - Further investigation of the aerial parts of Alomia myriadenia revealed an
      halimane diterpene identified as ent-8S,12S-epoxy-7R,16-dihydroxyhalima-5(10),13
      dien-15,16-olide along with the known ent-16-hydroxylabda-7,13-dien-15,16-olide,
      ent-12R-hydroxylabda-7,13-dien-15,16-olide, 6,7-methylenedioxycoumarin (ayapin),
      and kaempferol-7-methylether (rhamnocitrin). Evaluated in a panel of human cancer
      cell lines, the 16-hydroxylabade diterpene was the most active, showing an ED(50)
      value of 0.3 mug/ml against Lu1 (human lung cancer) cells. Tested in vitro
      against Trypanosoma cruzi in infected murine blood, this compound caused lysis of
      100% of the parasites at 250 mug/ml.

PMID- 14568081
TI  - Diterpenes and sesquiterpenes from the bark of Taxus yunnanensis.
AB  - Two taxane-type diterpenes, 10beta-acetoxy-2alpha,5alpha,7beta,9alpha
      tetrahydroxytaxa-4(20),11-dien-13-one and 2alpha-acetoxy-9alpha-benzoyloxy
      5alpha,7beta,10beta,15-tetrahydroxy-11(15-->1)- abeotaxa-4(20),11-dien-13-one,
      and two new drimane-type sesquiterpenes, 1beta-acetoxy-7-drimen-11alpha-ol-12,11
      lactone and 1beta-acetoxy-11,12-epoxy-6-drimen-8alpha,11alpha-diol, were isolated
      from the bark of Taxus yunnanensis together with 35 known taxane-type diterpenes,
      a known drimane-type sesquiterpene and a known flavanone.

PMID- 14568080
TI  - Flavonoid composition related to petal color in different lines of Clitoria
      ternatea.
AB  - Flavonoids in the petals of several C. ternatea lines with different petal colors
      were investigated with LC/MS/MS. Delphinidin 3-O-(2"-O-alpha-rhamnosyl-6"-O
      malonyl)-beta-glucoside was newly isolated from the petals of a mauve line (wm)
      together with three known anthocyanins. They were identified structurally using
      UV, MS, and NMR spectroscopy. Although ternatins, a group of 15 (poly)acylated
      delphinidin glucosides, were identified in all the blue petal lines (WB, BM-1,
      'Double Blue' and 'Albiflora'), WM accumulated delphinidin 3-O-(6"-O-malonyl)
      beta-glucoside instead. The white petal line (WW) did not contain anthocyanins.
      Quantitative data showed that the total anthocyanin contents in WB and 'Double
      Blue' were ca. 8- and 10-fold higher than that in BM-1, a bud mutant of 'Double
      Blue', respectively. The total anthocyanin content in 'Albiflora' was less than 2
      x 10(-3) times those in WB or 'Double Blue'. While all the lines contained the
      same set of 15 flavonol glycosides in similar relative ratios, the relative ratio
      of myricetin glycosides in ww and 'Albiflora' was ca. 30-70 times greater than
      those in the other lines. The change in flower color from blue to mauve was not
      due to a change in the structure of an anthocyanidin from delphinidin, but to the
      lack of (polyacylated) glucosyl group substitutions at both the 3'- and 5'
      positions of ternatins. This implies that glucosylation at the 3'- and 5'
      positions of anthocyanin is a critical step in producing blue petals in C.
      ternatea.

PMID- 14568082
TI  - Xanthones from the stem bark of Garcinia nigrolineata.
AB  - Nine xanthones, nigrolineaxanthones A-I, together with nine known xanthones, were
      isolated from the crude methanol extract of the stem bark of Garcinia
      nigrolineata; two of which have previously been reported as synthetic xanthones.
      The structures were elucidated by analysis of spectroscopic data, especially
      using 1D and 2D NMR spectroscopic data.

PMID- 14568083
TI  - Ratio of erythro and threo forms of beta-O-4 structures in tension wood lignin.
AB  - The ratio of erythro and threo forms of beta-O-4 structures in tension wood
      lignin was investigated by ozonation analysis of wood meal taken from various
      positions in the stem of yellow poplar (Liriodendron tulipifera). The proportion
      of the erythro form was higher in tension wood than in opposite wood, and the
      methoxyl group content showed a similar trend. The proportion of the erythro form
      and the methoxyl group content in the 7 positions in the stem lignin was
      correlated (correlation coefficient R=0.98), suggesting that the type of aromatic
      ring, syringyl or guaiacyl, is one of the factors which stereochemically controls
      the ratio of erythro and threo forms of beta-O-4 structures during lignin
      formation.

PMID- 14568084
TI  - Evidence for cross-linking in tomato cutin using HR-MAS NMR spectroscopy.
AB  - Cutin is a polyester biopolymer component of plant leaf and fruit cuticles, most
      often associated with waxes and cuticular polysaccharides, and sometimes with
      another aliphatic biopolymer called cutan. Insolubility of these cuticular
      biopolymers has made it difficult to apply traditional analytical techniques for
      structure determination, because most techniques providing molecular level
      details require solubility. By using the relatively new technique of one and two
      dimensional high-resolution magic angle spinning (HR-MAS) NMR spectroscopy, with
      added information from solid-state 13C NMR spectroscopy, detailed through-bond
      connectivities and assignments are made for cutin from Lycopersicon esculentum
      (tomato) fruit. Based on the data obtained, tomato cutin is found to be
      predominantly an aliphatic polyester with some olefinic and aromatic moieties,
      consistent with previous studies that employed various degradative approaches.
      Aside from esters, there are free primary and secondary alcohol groups, as well
      as free fatty acids. A significant finding is the presence of alpha-branched
      fatty acids/esters. Mid-chain hydroxyls appear to be generally unesterified, but
      esters of mid-chain hydroxyls have been identified. The alpha-branched fatty
      acids/esters and esters of mid-chain hydroxyls could point towards cross-linking.

PMID- 14568091
TI  - Astigmatism in infant monkeys reared with cylindrical lenses.
AB  - To determine whether developing primate eyes are capable of growing in a manner
      that eliminates astigmatism, we reared infant monkeys with cylindrical spectacle
      lenses in front of one or both eyes that optically simulated with-the-rule,
      against-the-rule, or oblique astigmatism (+1.50-3.00x90, x180, x45 or x135).
      Refractive development was assessed by retinoscopy, keratometry and A-scan
      ultrasonography. In contrast to control monkeys, the cylinder-lens-reared monkeys
      developed significant amounts of astigmatism. The astigmatism was corneal in
      nature, bilaterally mirror symmetric and oblique in axis, and reversible. The
      ocular astigmatism appeared to be due to a reduction in the rate of corneal
      flattening along the steeper meridian while the other principal meridian appeared
      to flatten at a more normal rate. However, regardless of the orientation of the
      optically imposed astigmatism, the axis of the ocular astigmatism was not
      appropriate to compensate for the astigmatic error imposed by the treatment
      lenses. Our results indicate that visual experience can alter corneal shape, but
      there was no evidence that primates have an active, visually regulated
      "sphericalization" mechanism.

PMID- 14568092
TI  - Observer strategies in perception of 3-D shape from isotropic textures:
      developable surfaces.
AB  - We document the limitations of isotropic textures in conveying three-dimensional
      shape. We measured the perceived shape and pitch of upright and pitched
      corrugated surfaces overlaid with different classes of isotropic textures:
      patterns containing isotropic texture elements, isotropically filtered noise
      patterns, and patterns containing ellipses or lines of all orientations.
      Frequency modulations arising from surface slant were incorrectly interpreted as
      changes in surface distance, resulting in concavities being misclassified as
      convexities, and right and left slants as concavities. In addition, images of
      pitched surfaces exhibited oriented flows that confound surface shape and surface
      pitch. Observers related oriented flow patterns to particular surface shapes with
      a bias for perceiving convex surfaces. When concave and convex curvatures were
      concurrently visible, the number of correct shape classifications increased
      slightly. Isotropic textures thus convey correct 3-D shapes of developable
      surfaces only in some conditions, and the same perceptual strategies lead to non
      veridical percepts in other conditions.

PMID- 14568093
TI  - Expectancy effects on spatial frequency processing.
AB  - We explored top-down modulation of spatial frequency (SF) processing. When
      auditory pre-cueing directed observers' attention to one of two 4-octaves (SF)
      apart plaid components observers tended to perceive the cued component,
      suggesting selective attention to the SF channel they expected to carry task
      relevant information. In agreement, pre-cueing had no effect with components
      often processed by the same channel (0.5-octaves apart). Further, effects of
      expectancy were greater than of uncertainty and were SF tuned. Combined our
      findings suggest top-down modulation of early, cortical, SF processing. We argue
      this could similarly explain the previously reported influences of categorisation
      on SF processing.

PMID- 14568094
TI  - Unconscious adaptation: a new illusion of depth induced by stimulus features
      without depth.
AB  - Here, we show a new illusion of depth induced by psychophysical adaptation to
      dynamic random-dot stereograms (RDS) that are interocularly anticorrelated (i.e.,
      in which the images for the two eyes have reversed contrast polarity with each
      other). After prolonged viewing of anticorrelated RDS, the presentation of
      uncorrelated RDS (i.e., in which two images are mutually independent random-dot
      patterns) produces the sensation of depth, although both anticorrelated and
      uncorrelated RDSs are perceptually rivalrous with no consistent depth by
      themselves. Contrary to other aftereffects demonstrated in a number of visual
      dimensions, including motion, orientation, and disparity, this illusion results
      from unconscious adaptation; observers are not aware of what they are being
      adapted to during the process of adaptation. We further demonstrate that this
      illusion can be predicted from the simulated responses of disparity-selective
      neurons based on a local filtering model. Model simulations indicate that the
      inspection of anticorrelated RDS causes the adaptation of all disparity detectors
      except one sensitive to its disparity; therefore, those selectively unadapted
      detectors show relatively strong activation in response to the subsequent
      presentation of uncorrelated RDS and produce depth perception.

PMID- 14568095
TI  - Face processing in 8-month-old infants: evidence for configural and analytical
      processing.
AB  - Two experiments examined whether 8-month-old infants process faces (photos in
      Experiment 1, schematic faces in Experiment 2) analytically by processing facial
      features independently of the facial context or configurally by processing the
      features in conjunction with the facial context. Infants were habituated to two
      faces and looking time was measured. After habituation they were tested with a
      habituation face, a switch face, or a novel face. In the switch faces, single
      features of the habituation faces were switched. The results showed that the
      infants processed facial features of photographs of faces configurally whereas
      they processed features of schematic faces (eyes, nose, facial contour)
      analytically. Thus, although infants have access to both processing modes, for
      real looking faces they use the configural mode.

PMID- 14568096
TI  - The efficiency of speed discrimination for coherent and transparent motion.
AB  - Transparent motion involves the integration and segmentation of local motion
      signals. Previous research found a cost for processing transparent random dot
      motions relative to single coherent motions. However, this cost can be the result
      of the increased complexity of the transparent stimuli. We investigated this
      possibility by measuring the efficiency of transparent and coherent motions.
      Since efficiency normalises human performance to that of an ideal observer in the
      same task, performance can be compared fairly across tasks. Our task, identical
      in both transparent and coherent conditions, was to discriminate the fastest
      speed between two opposite motion directions. In two experiments where we varied
      dot density and speed, we confirmed the cost in human sensitivity for transparent
      motion but also found a cost for the ideal observer. The outcome was a consistent
      residual cost in efficiency for transparent motion. This result points to a
      processing limitation for transparent motion analogous to previously suggested
      inhibitory mechanisms between opposite directions of motion. Furthermore, we
      found that both transparent and coherent motion efficiencies decreased as dot
      density increased. This latter result stresses the importance of the
      correspondence problem and suggests that local motion signals are integrated over
      large areas.

PMID- 14568097
TI  - A model using MT-like motion-opponent operators explains an illusory
      transformation in the optic flow field.
AB  - Previous studies have shown that a physiologically based model using motion
      opponent operators to compute heading performs accurately for simulated observer
      translations. Here we show how this model can explain an illusory shift in the
      perceived focus of expansion of a radial flow field that occurs when a field of
      laterally moving dots is superimposed on a field of radially moving dots.
      Furthermore, we can use the model to predict the perceptual shift of the focus of
      expansion for novel visual stimuli. These results support the hypothesis that
      this illusion results from motion subtraction during the processing of optic flow
      fields.

PMID- 14568098
TI  - Visual processing of rapidly presented stimuli is normalized in Parkinson's
      disease when proximal stimulus strength is enhanced.
AB  - Deficient perception and cognition in Parkinson's disease (PD) has been
      attributed to slow information processing, but an alternative explanation may be
      reduced signal strength. In 18 nondemented individuals with PD and 15 healthy
      adults, we enhanced the contrast level of rapidly flashed masked letters. The PD
      group required significantly higher contrast to reach criterion (80% accuracy).
      Normal motion detection in these participants indicated no gross, general
      dysfunction of the dorsal visual processing stream. These results suggest that
      putatively slowed processing in PD may be an artifact of reduced signal strength
      arising from depletion of dopamine in retina or cortical visual areas.

PMID- 14568099
TI  - Is word recognition different in central and peripheral vision?
AB  - Peripheral vision plays an important role in normal reading, but its role becomes
      larger for visually impaired people with central-field loss. This experiment
      studied whether lexical processing differs in central and peripheral vision
      through the analysis of word-frequency effects in lexical decisions. We asked two
      main questions: (1) Do central and peripheral vision differ in the time course of
      lexical processing? and (2) do central and peripheral vision differ in the
      quality of lexical processing? To address the first question, we examined the
      time course of frequency effects in central and peripheral vision over a range
      from 25 to 500 ms. We found that significant frequency effects occurred for the
      shortest exposures, 25-50 ms, in central vision, whereas significant frequency
      effects did not occur in peripheral vision until 100 ms. To address the second
      question, we used word-frequency effects as a marker for the nature of lexical
      processing. We compared frequency effects in central and peripheral vision for
      data within matched ranges of percent accuracy (0-20%, 20-40%, 40-60%, 60-80%,
      and 80-100%). We found that there was no difference in the pattern of frequency
      effects in central and peripheral vision at equivalent performance levels. We
      conclude that lexical processing is slower in peripheral vision, but the quality
      of lexical processing is similar in central and peripheral vision.

PMID- 14568100
TI  - Differential activities of Sonic hedgehog mediated by Gli transcription factors
      define distinct neuronal subtypes in the dorsal thalamus.
AB  - The dorsal thalamus (DT) is a pivotal region in the vertebrate brain that relays
      inputs from the peripheral sensory organs to higher cognitive centers. It
      consists of clusters of neurons with relevant functions, called brain nuclei.
      However, the mechanisms underlying development of the DT, including specification
      of the neuronal subtypes and morphogenesis of the nuclear structures, remain
      largely unknown. As a first step to this end, we focused on two transcription
      factors Sox14 and Gbx2 that are expressed in the specific brain nuclei in the
      chick DT. The onset of their expression was found in distinct populations of the
      postmitotic cells in the prosomere 2, which was regulated by the differential
      activities of Sonic hedgehog (Shh) in a manner consistent with the action as a
      morphogen. Furthermore, both gain- and loss-of-function results strongly suggest
      that such distinct inductive activities are mediated selectively by different Gli
      factors. These results suggest that cooperation of the differential expression of
      Gli factors and the activity gradient of Shh signaling generates the distinct
      thalamic neurons at the specific locations.

PMID- 14568101
TI  - Conserved cis-regulatory modules mediate complex neural expression patterns of
      the eyeless gene in the Drosophila brain.
AB  - The Drosophila Pax-6 homologs eyeless (ey) and twin of eyeless (toy) are
      expressed in the eyes and in the central nervous system (CNS). In addition to the
      pivotal functions in eye development, previous studies revealed that ey also
      plays important roles in axonal development of the mushroom bodies, centers for
      associative learning and memory. It has been reported that a second intron
      enhancer that contains several Pax-6 binding sites mainly controls the eye
      specific expression, but the DNA sequences that control CNS expression are
      unknown. In this work, we have dissected transcriptional enhancer elements of the
      ey gene that are required for the CNS expression in various developmental stages.
      We first show that CNS expression is independent of the eye-specific enhancer of
      the second intron. By systematic reporter studies, we have identified several
      discrete DNA elements in the 5' upstream region and in the second intron that
      cooperatively interact to generate most of the ey expression pattern in the CNS.
      DNA sequence comparison between the ey genes of distant Drosophila species has
      identified conserved modules that might be bound by the upstream regulatory
      factors of the ey gene in CNS development. Furthermore, by RNA interference and
      mutant studies, we show that ey expression in the brain is independent of the
      activity of toy and ey itself whereas in the eye primordia it requires both,
      supporting the notion that ey and toy are regulated by parallel and independent
      regulatory cascades in brain development.

PMID- 14568102
TI  - VegT activation of the early zygotic gene Xnr5 requires lifting of Tcf-mediated
      repression in the Xenopus blastula.
AB  - Xenopus Nodal-related (Xnr) 5 is one of the earliest expressed components of a
      network of TGF-beta factors participating in endoderm and mesoderm formation.
      Zygotic gene expression is not required for induction of Xnr5; rather, expression
      is dependent on the maternal factors VegT, localised throughout the vegetal pole,
      and beta-catenin, functional in the future dorsal region of the embryo. Using
      transient assays with a luciferase reporter in Xenopus embryos, we have defined a
      minimal promoter, which mimics the response of the endogenous gene to applied
      factors. Expression of luciferase from the minimal promoter is dorsal-specific
      and requires two T-box half sites and a functional beta-catenin/XTcf-3 pathway.
      Mutation of two Tcf/Lef sites in the minimal promoter permits induction by VegT
      to wild-type promoter levels in the presence of a dominant-negative XTcf-3,
      indicating that beta-catenin/XTcf-3 are repressive and are not required as
      transactivators of Xnr5 transcription. The activity of the Tcf/Lef mutant
      promoter is similar in both ventral and dorsal sides of the embryo. In transgenic
      experiments, the dorsal specificity of expression of a beta-gal reporter driven
      by the wild-type minimal promoter is abolished upon mutation of these Tcf/Lef
      sites. We propose a model in which XTcf-3 functions as a repressor of Xnr5
      throughout the blastula embryo, except where repression is lifted by the binding
      of beta-catenin in the dorsal region. This removal of repression allows
      activation of the promoter by VegT in the dorsal vegetal region. Subsequently,
      zygotically expressed LEF1 supersedes the role of beta-catenin/XTcf-3.

PMID- 14568103
TI  - The Drm-Bowl-Lin relief-of-repression hierarchy controls fore- and hindgut
      patterning and morphogenesis.
AB  - The elucidation of pathways linking patterning to morphogenesis is a problem of
      great interest. We show here that, in addition to their roles in patterning and
      morphogenesis of the hindgut, the Drosophila genes drumstick (drm) and bowl are
      required in the foregut for spatially localized gene expression and the
      morphogenetic processes that form the proventriculus. drm and bowl belong to a
      family of genes encoding C(2)H(2) zinc finger proteins; the other two members of
      this family are odd-skipped (odd) and sob. In both the fore- and hindgut, drm
      acts upstream of lines (lin), which encodes a putative transcriptional regulator,
      and relieves its repressive function. In spite of its phenotypic similarities
      with drm, bowl was found in both foregut and hindgut to act downstream, rather
      than upstream, of lin. These results support a hierarchy in which Drm relieves
      the repressive effect of Lin on Bowl, and Bowl then acts to promote spatially
      localized expression of genes (particularly the JAK/STAT pathway ligand encoded
      by upd) that control fore- and hindgut morphogenesis. Since the odd-family and
      lin are conserved in mosquito, mouse, and humans, we propose that the odd-family
      genes and lin may also interact to control patterning and morphogenesis in other
      insects and in vertebrates.

PMID- 14568104
TI  - Scleraxis (Scx) directs lacZ expression in tendon of transgenic mice.
AB  - Scleraxis is a transcription factor expressed during early periods of mouse
      tendon morphogenesis. We have determined that tendon is first clearly present in
      mouse limb at embryonic day 14.5 (E14.5) and, by in situ hybridization, that
      scleraxis is expressed in the mouse tendons at E14.5. We have also investigated
      the regulatory elements that direct scleraxis gene expression to the limb
      tendons. DNA constructs were engineered such that the lacZ reporter gene was
      expressed under the control of portions of scleraxis regulatory regions.
      Transgenic mice carrying these constructs were made and expression of the
      construct was monitored by staining for beta-galactosidase activity. A construct
      containing 7 Kbp of 5' flanking sequence, the intron, both exons and 1.8 Kbp of
      3' flanking sequence was expressed in a pattern that closely resembled the
      endogenous scleraxis gene. Mouse embryos carrying this construct expressed lacZ
      in their limb flexor and extensor tendons at E14.5. The lacZ stain in tendon was
      readily distinguished from -muscle using an anti-myosin heavy chain antibody to
      visualize muscle. Deletion of the intron, exons and 3' flanking region did not
      affect the pattern of tendon expression in the limbs of E14.5 transgenic mice.
      Additional constructs which deleted 5' flanking sequences up to -355 bp from the
      published cDNA sequence, showed limb tendon expression that was similar to the
      endogenous gene. When an additional 160 bp were deleted so that only
      approximately 200 bp of 5' flanking region was directing lacZ expression, no beta
      galactosidase activity was observed in the tendons.

PMID- 14568105
TI  - Expression and function of a starfish Otx ortholog, AmOtx: a conserved role for
      Otx proteins in endoderm development that predates divergence of the
      eleutherozoa.
AB  - The sea urchin orthodenticle (Otx)-related transcription factor is an early
      activator of other endomesodermally expressed transcription factors. Its normal
      function is required for the development of the archenteron and to lock cells
      into endomesodermal fate. To determine if this is a basal Otx function in
      echinoderms we have studied the role of an Otx ortholog in a starfish, Asterina
      miniata. The patterns of AmOtx expression are found to be similar, in many
      details, to those reported for other indirectly developing echinoderms and
      hemichordates, suggestive of a conserved function both in endoderm development
      and ciliary band formation in these two phyla. When downstream targets of the
      AmOtx protein are suppressed using a dominant engrailed repressor strategy,
      embryos fail to develop the endodermal component of the archenteron, though
      initial phases of mesoderm development proceed normally. The function of Otx
      proteins in endodermal development at least predated the evolution of the free
      living echinoderms (Eleutherozoa).

PMID- 14568106
TI  - Developmental role of HMGN proteins in Xenopus laevis.
AB  - HMGN proteins are architectural chromatin proteins that reduce the compaction of
      the chromatin fiber, facilitate access to nucleosomes and modulate replication
      and transcription processes. Here we demonstrate that in Xenopus laevis, the
      expression and cellular location of the HMGN proteins are developmentally
      regulated and that their misexpression leads to gross developmental defects in
      post-blastula embryos. HMGN transcripts and proteins are present throughout
      oogenesis; however, the proteins stored in the cytoplasm are not associated with
      lampbrush chromosomes, and are rapidly degraded when oocytes mature into eggs.
      During embryogenesis, HMGN expression is first detected in blastula stages and
      progresses to a tissue-specific expression reaching relative high levels in the
      mesodermal and neuroectodermal regions of tadpoles. Only after midblastula
      transition (MBT), alterations in the HMGN levels by either microinjection of
      recombinant proteins or by morpholino-antisense oligo treatments produced embryos
      with imperfectly closed blastopore, distorted body axis and showed abnormal head
      structures. Analyses of animal cap explants indicated that HMGN proteins are
      involved in the regulation of mesoderm specific genes. In addition, HMGN
      misexpression caused altered expression of specific genes at MBT rather than
      global changes of transcription rates. Our results demonstrate that proper
      embryonic development of Xenopus laevis requires precisely regulated levels of
      HMGN proteins and suggest that these nucleosomal binding proteins modulate the
      expression of specific genes.

PMID- 14568107
TI  - A targeted gain of function screen in the embryonic CNS of Drosophila.
AB  - In order to identify genes involved in the development of the central nervous
      system (CNS) we have undertaken a gain of function screen in the embryonic CNS of
      Drosophila. Transposable P-elements and the UAS/GAL4 system were used to initiate
      transcription of genes in a pan-neural pattern using scaGAL4. Over 4100
      individual P-element insertion lines were screened with monoclonal antibodies
      BP102 and 1D4 to visualize axon pathways. Twenty-five P-element insertions
      corresponding to 18 genes resulted in aberrant CNS axon pathfinding when
      misexpressed with scaGAL4. Genes involved in axon guidance, embryonic patterning,
      and cell cycle regulation were isolated. In addition, we identified several zinc
      finger transcription factors not previously implicated in axon guidance or CNS
      development. This group includes Squeeze, Kruppel homolog-1, Hepatocyte nuclear
      factor 4, and two uncharacterized genes, CG11966 and CG9650. Calnexin99A, a
      putative molecular chaperone, was isolated as well.

PMID- 14568109
TI  - Auditory-visual speech perception examined by fMRI and PET.
AB  - Cross-modal binding in auditory-visual speech perception was investigated by
      using the McGurk effect, a phenomenon in which hearing is altered by incongruent
      visual mouth movements. We used functional magnetic resonance imaging (fMRI) and
      positron emission tomography (PET). In each experiment, the subjects were asked
      to identify spoken syllables ('ba', 'da', 'ga') presented auditorily, visually,
      or audiovisually (incongruent stimuli). For the auditory component of the
      stimuli, there were two conditions of intelligibility (High versus Low) as
      determined by the signal-to-noise (SN) ratio. The control task was visual talker
      identification of still faces. In the Low intelligibility condition in which the
      auditory component of the speech was harder to hear, the visual influence was
      much stronger. Brain imaging data showed bilateral activations specific to the
      unimodal auditory stimuli (in the temporal cortex) and visual stimuli (in the
      MT/V5). For the bimodal audiovisual stimuli, activation in the left temporal
      cortex extended more posteriorly toward the visual-specific area in the Low
      intelligibility condition. The direct comparison between the Low and High
      audiovisual conditions showed increased activations in the posterior part of the
      left superior temporal sulcus (STS), indicating its relationship with the
      stronger visual influence. It was discussed that this region is likely to be
      involved in cross-modal binding of auditory-visual speech.

PMID- 14568108
TI  - Nucleoprotamine diet derived from salmon soft roe protects mouse hippocampal
      neurons from delayed cell death after transient forebrain ischemia.
AB  - The nutritional benefits of nucleoprotamine (NP), the main component of fish soft
      roe, have been rarely addressed. In the present study, the preventive effect of
      oral supplements of nucleoprotamine and its derivatives, DNA and protamine (PT),
      extracted from salmon soft roe, on survival rate and hippocampal cell death
      induced by transient brain ischemia, was evaluated in mice. Artificially
      formulated nucleoprotamine-free (NF) diet with/without nucleoprotamine, DNA or
      protamine was fed orally. One week after commencement of respective diets,
      animals were subjected to transient brain ischemia, which was performed by common
      carotid artery (CCA) occlusion for 25 (severe) or 15 min (mild). After severe
      ischemia, the survival rate of the NF group was lower than that in the group fed
      standard diet or NP. Morphological changes in the hippocampal CA1 region were
      estimated 48 h after mild ischemia. The NP and PT groups significantly decreased
      the neuronal damage compared with the NF group. The number of cell death in the
      DNA group, however, was affected similar to that of the NF group. Our data
      suggests that the nucleoprotamine content in salmon soft roe could be a useful
      nutritional resource for the prevention of cell damage caused by ischemia such as
      those occurring with cerebral and/or heart infarction.

PMID- 14568110
TI  - Effects of neuromuscular blocking agents on central respiratory control in the
      isolated brainstem-spinal cord of neonatal rat.
AB  - Although neuromuscular blocking agents (NMBAs) function as muscular nicotinic
      acetylcholine receptor (nAChR) antagonists, several studies have shown that they
      block neuronal nAChRs as well, which led us to hypothesize that these agents can
      affect neuronal nAChRs expressed in respiratory centers. To test this hypothesis,
      we studied the effects of two NMBAs on respiratory activity and respiratory
      neurons in brainstem-spinal cord preparations from neonatal rats. The application
      of either D-tubocurarine or vecuronium resulted in dose-dependent reductions in
      C4 respiratory rate. These reductions were concomitant with reductions in the
      depolarizing cycle rate of inspiratory (Insp) neurons; the depolarizing cycle
      rate of preinspiratory (Pre-I) neurons, however, was not affected. We also
      detected C4 burst activity during the depolarizing phase in Pre-I neurons, even
      during NMBA-induced respiratory depression. Both NMBAs inhibited drive potential
      amplitude and intraburst firing frequency in Insp and Pre-I neurons. These agents
      also induced a hyperpolarization and an increase in membrane resistance in Pre-I
      neurons, however they had no effect on these membrane properties in Insp neurons.
      Our findings indicate that these agents suppress central respiratory activity
      mainly through their inhibitory effects on Pre-I neurons and the Pre-I to Insp
      neuron synaptic drive, and that nAChRs are involved in central respiratory
      control.

PMID- 14568111
TI  - The light and electron microscopic characterisation of identified striato
      ventrotegmental projection neurons in the domestic chick (Gallus domesticus).
AB  - A major projection of the medial striatum (lobus parolfactorius, LPO) of birds is
      the striato-ventrotegmental pathway projecting to the area ventralis tegmentalis.
      In the present study, we investigated the morphology and connectivity of striato
      ventrotegmental neurons in the medial LPO. The neurons were identified by
      injecting the fluorescent retrograde tracer fast blue (FB) into the area
      ventralis tegmentalis. FB-labelled neurons in the LPO were targeted and
      iontophoretically injected with lucifer yellow (LY) in paraformaldehyde fixed
      slices. The fluorescent LY label in the filled neurons was then photoconverted,
      and the ultrastructure of cells was investigated. According to our results, the
      soma of striato-ventrotegmental neurons is rich in organelles, in particular
      rough and smooth endoplasmic reticula and they possess a large, unindented and
      slightly eccentric nucleus. The LY-labelled cells possess relatively few,
      sparsely spiny dendrites, and represent a type of medium-sized spiny projection
      neuron characteristic of the striata of birds. Axospinous synapses on the
      labelled cells are asymmetric and correspond morphologically to the glutamatergic
      excitatory type of terminals described previously in the LPO. Both symmetric and
      asymmetric axodendritic and axosomatic synapses were detected. Some symmetric
      synapses were GABA immunolabelled, whereas some asymmetric synapses were
      immunopositive to glutamate. Axon collaterals of labelled cells formed symmetric
      or asymmetric axodendritic synapses. Direct contact without interposing glial
      processes was observed between one of the FB-labelled neurons and an adjacent
      neuronal soma. There was also a microneuron attached to one of the labelled
      cells, which we identified as a neurogliaform 'dwarf' cell.

PMID- 14568112
TI  - Effects of ventrolateral-ventromedial thalamic lesions on motor coordination and
      spatial orientation in rats.
AB  - The ventrolateral-ventromedial (VL-VM) nuclei are classified as a motor area of
      the thalamus on the basis of predominant input from the cerebellum and the basal
      ganglia and output to the motor cortex. The sensitivity to electrolytic lesions
      of the VL-VM thalamic nuclei in rats was evaluated for tests requiring balance
      and equilibrium. VL-VM lesions impaired acquisition of the rotorod test but had
      no effect on stationary beam and hole-board tests. A selective impairment was
      also observed in the Morris water maze, as VL-VM thalamic lesions slowed down
      acquisition of the hidden platform but not the visible platform condition. These
      results support the hypothesis that thalamic motor nuclei participate in the
      acquisition of sensorimotor and spatial learning.

PMID- 14568113
TI  - Hiccup reflex is mediated by pharyngeal branch of glossopharyngeal nerve in cats.
AB  - Hiccup reflex is a coordinated motor activity that causes a brief strong
      inspiratory movement accompanied by glottic adduction. Our previous study has
      demonstrated that mechanical stimulation of the dorsal epipharynx elicits hiccup
      like response. To identify the afferent pathway of the hiccup-like response, the
      pharyngeal branch of the glossopharyngeal nerve (PB-GPN) which distributed to the
      dorsal epipharyngeal area was electrically stimulated in anesthetized,
      spontaneously breathing cats. To access the epipharynx and to directly observe a
      glottic movement, we made a submental opening at the region rostral to the
      epiglottis. An activity from the lateral cricoarytenoid (LCA) muscle of the
      larynx was recorded as an index of glottic adduction, and intrapleural pressure
      (Ppl) as an index of an inspiratory movement. Electrical stimulation of PB-GPN
      evoked a fixed motor pattern of hiccup-like response representing a spiky strong
      negative change in Ppl accompanied by an initial brief burst of LCA
      electromyogram (EMG). LCA excitation occurred prior to the spiky inspiratory
      movement. An initial and transient glottic adduction during the response was
      confirmed by direct observation. Electrical stimulation of the main trunk of the
      glossopharyngeal nerve evoked expiratory reflex, but not inspiratory (hiccup
      like) response. These results indicated that PB-GPN is responsible for hiccup
      reflex.

PMID- 14568114
TI  - The effects of alcohol intake and withdrawal on the seizures frequency and
      hippocampal morphology in rats with epilepsy.
AB  - The aim of our study, using the pilocarpine model of epilepsy, was to investigate
      the effects of alcohol administration and withdrawal on the spontaneous recurrent
      seizures (SRSs). Four groups of adult, male Wistar rats were studied: (A).
      control rats (n=10), received neither pilocarpine nor alcohol, (B). alcohol
      treated rats (n=10), received a daily dose of 3.0 g x kg(-1) of a 30% alcohol
      solution via an oesophagic probe for 30 days, (C). rats with epilepsy (n=10),
      (D). rats with epilepsy with alcohol intake (n=10). SRSs were induced by a single
      dose of pilocarpine (i.p.) and the basal frequency of SRSs was video monitored
      (24h per day) for 30 days. Following this period, the animals of group D received
      a daily dose of alcohol solution as described above and at the end of this
      period, alcohol administration was stopped and the seizure frequency was assessed
      for more 30 days. The basal seizure frequency observed in groups C and D during
      the first 30 days was 2.2+/-1.8 seizures per week per animal. In group D, it was
      observed an increase to 12.2+/-5.8 during the first 2 weeks of alcohol
      administration. During the last 2 weeks of alcohol administration, the number of
      SRSs returned to the previous basal level. During alcohol withdrawal the seizure
      frequency increased to 14.3+/-7.4 seizures per week per animal for the first 2
      weeks, and returned to the basal level in the remaining period of observation.
      The Neo-Timm and Nissl staining of hippocampal formation and of the dentate gyrus
      in rats with epilepsy showed a cell loss in the hippocampal subfield CA1 and in
      the hillus of dentate gyrus. In rats with epilepsy with alcohol intake, we
      observed a cell loss in hippocampal subfields CA3 and hillus of the dentate
      gyrus, with significant neuronal death in subfield CA1, when compared with
      control animals. The alcohol withdrawal syndrome is a crucial event for the
      development of functional and neuropathological alterations associated with
      epilepsy.

PMID- 14568115
TI  - Modulation of voltage-dependent potassium currents by opiates in facial
      motoneurons of neonatal rats.
AB  - We examined the modulation of rat facial motoneurons (FMNs) by opiates in a slice
      preparation (7-15 days old) using whole-cell patch clamp techniques. Although
      application of methionine enkephalin (ME) did not change the peak value of the
      transient outward current (A-current, IA), it reduced the persistent voltage
      dependent K(+) currents (IKs) in a dose-dependent manner. The reduction was
      antagonized by naloxone (40 microM). IKs were reduced only by mu-selective
      agonist [D-Ala(2),N-Me-Phe(4),Gly(5)-ol]enkephalin (DAMGO, 2-121.6 microM). This
      reduction was antagonized by naloxone (40 microM) or the mu-selective antagonist,
      D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Phe-Thr-NH(2) (CTOP, 1 microM). Agonists for other
      opiate receptors (delta- and kappa-opiate receptor) showed no effect on IKs. In
      accord with the effects on IKs, DAMGO (100 microM) prolonged the duration of the
      action potential evoked in Ca(2+)-free external solution containing 4
      aminopiridine (1mM). These results suggest that the activation of mu-opiate
      receptors contributes to signal transduction in FMNs primarily by modulating
      action potential duration.

PMID- 14568116
TI  - Endogenous glutamatergic synaptic activity elicits acetylcholine release from rat
      cultured septal cells.
AB  - We tested the characteristics of acetylcholine (ACh) release from cultured rat
      septal cells. The spontaneous release was inhibited by treatment with
      tetrodotoxin (TTX) and omega-conotoxin (GVIA), indicating that the release was
      elicited by synaptic activity. The release was also inhibited by 6-cyano-7
      nitroquinoxaline-2,3-dione (CNQX), an alpha-amino-3-hydroxy-5-methyl-4-isoxazole
      propionic acid (AMPA) receptor blocker, in both the absence and presence of nerve
      growth factor (NGF), suggesting that endogenously released glutamate produced the
      ACh release by stimulating AMPA receptors. This is the first report of detection
      of the release of ACh by endogenous spontaneous synaptic activity conducted by
      glutamate AMPA receptor activation in cultured septal cells. This in vitro
      experimental system is useful for the study of cholinergic functions.

PMID- 14568117
TI  - Nicotine upregulates nerve growth factor expression and prevents apoptosis of
      cultured spinal cord neurons.
AB  - Modulation of neurotrophic factor expression may constitute an important part of
      neuroprotective effects of nicotine. Therefore, the effects of nicotine on
      expression of nerve growth factor (NGF) and its receptor, tyrosine receptor
      kinase A (trkA), were studied in cultured spinal cord neurons treated with
      arachidonic acid. Because injury to spinal cord is associated with elevated
      levels of arachidonic acid, this cell culture system has been developed in our
      laboratory as an in vitro model of neuronal injury in spinal cord trauma.
      Treatment with nicotine markedly upregulated NGF mRNA and protein expression in
      spinal cord neurons. In addition, a 12h treatment with nicotine increased mRNA
      levels of trkA. Both nicotine and exogenous NGF inhibited arachidonic acid
      induced apoptosis of spinal cord neurons. However, the blockage of the trkA
      receptor prevented nicotine-mediated anti-apoptotic effects. The present results
      indicate that increased expression of NGF may be an important element of the
      neuroprotective effects of nicotine in injured spinal cord neurons.

PMID- 14568118
TI  - Different susceptibility of facilitatory and inhibitory spinal pathways to
      ischemia in the cat.
AB  - The sensitivity of different excitatory and inhibitory segmental reflex pathways
      to ischemia was investigated by monosynaptic reflex testing in the spinal cat.
      Spinal cord ischemia was established by aortal snare occlusion of 1-10 min
      duration. Excitatory and inhibitory spinal pathways showed statistically
      significant different susceptibility to ischemic impact. In the period of
      decreasing responses after the onset of ischemia the transmission through oligo-
      or polysynaptic, facilitatory or inhibitory pathways was found to be depressed
      earlier than that of monosynaptic pathways. The period from the end of ischemia
      until the beginning of recovery of reflex effects was significantly longer for
      inhibitory effects, compared to the monosynaptic reflexes alone.The results
      indicated that interneurones of excitatory segmental pathways may be less
      sensitive to ischemia than motoneurones, and motoneurones seem to be less
      sensitive to ischemia than interneurones of inhibitory pathways. In high spinal
      animals, with a relatively high level of extensor inhibition, the enhanced
      excitability of inhibitory interneurones to GS motoneurones may be responsible
      for their sensitivity to ischemia, due to an increased rate of O(2) consumption
      and exhaustion of high-energy phosphate resources.

PMID- 14568119
TI  - Seeing what we never looked for.

PMID- 14568120
TI  - Fate of neutralizing and binding antibodies to IFN beta in MS patients treated
      with IFN beta for 6 years.
AB  - An increasing number of evidence is showing that during prolonged treatment of
      relapsing-remitting multiple sclerosis (RRMS) with interferon (IFN) beta 1a or
      IFN beta 1b, the patients may develop serum anti-IFN antibody. It has been argued
      that some of the RRMS patients receiving IFN beta, who developed antibodies to
      IFN, lose them over time even though the treatment continues. To gain further
      insights into this issue, we performed a study to establish what happened to
      binding antibodies (BAB) and neutralizing antibodies (NAB) in 42 RRMS patients
      treated for 6 years with IFN beta 1a and/or IFN beta 1b. While the data of BAB
      analysis did not allow to reach definite conclusions, the results on NAB
      development confirm that the presence of this type of antibodies is transitory;
      in fact, most of the positive patients reverted to seronegative, although the IFN
      treatment is still ongoing; the only patients who were positive for NAB at 6
      years of treatment are those whose serum contains high concentration of them. The
      paper also shows that patients lose antibodies to IFN independently on the type
      of IFN used for the treatment. In conclusion, the data indicate that the
      disappearance of the anti-IFN antibodies from the serum while the patients are
      still undergoing IFN treatment depends on the titer of antibodies but not on the
      type of IFN administered.

PMID- 14568121
TI  - Differential diagnosis of patients with intracranial sinus venous thrombosis
      related isolated intracranial hypertension from those with idiopathic
      intracranial hypertension.
AB  - In patients presenting with intracranial hypertension without hydrocephalus, mass
      lesions, and with normal cerebrospinal fluid (CSF) composition (pseudotumor
      cerebri syndrome), the diagnosis of intracranial sinus venous thrombosis (ISVT)
      has crucial etiological, therapeutic and prognostic implications. Utilizing two
      well-defined groups of pseudotumor cerebri patients, one with magnetic resonance
      imaging (MRI) or angiography confirmed ISVT (17 patients) and the other in whom
      ISVT has been excluded (idiopathic intracranial hypertension [IIH], 27 patients),
      we investigated the characteristics that might be helpful in distinguishing them.
      No clinical or auxiliary findings differed between the ISVT and IIH groups except
      for female gender and lower CSF protein level, which were significantly
      associated with the latter. While the syndrome pseudotumor cerebri could be due
      to multiple causes including ISVT, the term IIH should be restricted for patients
      with isolated intracranial hypertension attributable to no other neurological or
      systemic disease. Since CT frequently misses ISVT, patients with pseudotumor
      cerebri syndrome should undergo MRI and MR venography before being labeled as
      IIH. We conclude that Modified Dandy's Diagnostic Criteria of pseudotumor
      cerebri, formulated prior to MRI era, can no longer be applied for the diagnosis
      of IIH.

PMID- 14568122
TI  - Chronic stroke motor recovery: duration of active neuromuscular stimulation.
AB  - Active neuromuscular stimulation is an effective behavioral intervention for
      motor recovery improvements after a stroke. However, the most effective active
      neuromuscular stimulation durations have not been determined. The present
      experiment investigated active stimulation durations (0, 5, and 10 s) coupled
      with bilateral movements on progress toward motor recovery in wrist and finger
      extension. Twenty-six stroke survivors with chronic hemiparesis were randomly
      assigned to the stimulation duration groups, and subjects completed 4 days of
      rehabilitation training over a 2-week period. Mixed design analyses of variance
      on the Box and Block scores, chronometric reaction times, and force modulation of
      the sustained muscle contraction task revealed distinct motor recovery
      improvements for both the 5 and 10 s stimulation duration groups in comparison to
      the 0 s duration control group. Further, the number of blocks moved by the 10-s
      duration group exceeded those moved by the 5-s duration group. In conclusion, the
      5 and 10 s duration active stimulation/bilateral movement groups decreased
      residual motor dysfunctions that persisted beyond 12 months post stroke.

PMID- 14568123
TI  - 1H-MR spectroscopy: a promising method in distinguishing subgroups in temporal
      lobe epilepsy?
AB  - Proton MR spectroscopy offers an additional noninvasive method of supporting
      focus lateralization in patients with intractable temporal lobe epilepsy. In this
      study involving 57 patients, the ability of multivoxel 1H-MRS to differentiate
      between mesial and lateral TLE was investigated in addition to its ability to
      lateralize the epileptogenic focus. Temporal lobe epilepsy (TLE) was classified
      into mesiobasal or lateral temporal lobe epilepsy according to the results of
      preoperative diagnostics including neurological and neuropsychological
      examinations, video-EEG monitoring and high resolution MRI. 1H-MR-spectroscopy
      (1H-MRS) showed that pathological changes in the mesial temporal lobes indicate a
      predominance in different parts of the ipsilateral temporal lobe (hippocampal and
      parahippocampal areas) correlating to the clinically defined groups. In addition,
      mesiobasal TLE tends to have higher concomitant contralateral abnormalities. Our
      results reveal that 1H-MRS is able to distinguish between mesiobasal and lateral
      pathologies in patients with TLE and represents a useful tool for noninvasive TLE
      classification.

PMID- 14568124
TI  - Absence of detection of varicella-zoster virus DNA in temporal artery biopsies
      obtained from patients with giant cell arteritis.
AB  - It has been suggested that Varicella-Zoster virus (VZV) may play a role in the
      pathogenesis of giant cell arteritis (GCA). We therefore used both in situ
      hybridisation and in situ Polymerase Chain Reaction amplification techniques in
      an attempt to identify VZV DNA in 15 temporal arteries from histologically proven
      GCA. We did not detect evidence of VZV DNA in the arteries of any of these
      subjects, nor in temporal arteries obtained from seven normal control subjects.
      VZV was detected, however, in neurons in a human trigeminal ganglion. While
      sampling variation and sensitivity issues are likely to play a role in the
      discrepancies observed in different studies of VZV in GCA, this study does not
      provide further support for the notion that VZV is playing a significant part in
      causing GCA.

PMID- 14568125
TI  - The neuroprotective effect of ONO-1714 on NMDA-mediated cytotoxicity in vitro.
AB  - We report the effects of a newly developed NOS inhibitor on the neurotoxicity
      induced by NMDA on cultured fetal rat cortical neurons. To date, three different
      isoforms of NOS have been characterized. It has been considered that both
      neuronal NOS and inducible NOS activities are detrimental to the ischemic brain,
      whereas endothelial NOS plays a prominent role in maintaining cerebral blood flow
      and prevents neuronal injury during ischemia. ONO-1714 is a newly developed
      competitive NOS inhibitor that has selective inhibitory potency for iNOS than
      eNOS. However, its effect on nNOS has not been investigated yet. In this study,
      we investigated the neuroprotective effect of ONO-1714 on NMDA-induced
      neurotoxicity in our established model of primary cultured cortical neurons of
      rat foetus. Cortical neurons (prepared from E16 rat foetuses) were used after 13
      14 days in culture. The cells were exposed to 30 muM NMDA for 24 h in the
      culture. To evaluate the neuroprotective effects of NOS inhibitors, ONO-1714 and
      L-NAME, neurons were exposed to various concentrations of an NOS inhibitor with
      30 muM NMDA. The NMDA induced neurotoxicity was significantly attenuated by ONO
      1714 in all concentrations, but not in low to moderate concentrations of L-NAME.
      These findings demonstrate that the neuroprotective effect of ONO-1714 was more
      potent than L-NAME. Moreover, ONO-1714 has a strong inhibitory effect on nNOS and
      would be a powerful tool for the protection of neurons against cerebral ischemia.

PMID- 14568126
TI  - Glatiramer acetate-reactive T cells produce brain-derived neurotrophic factor.
AB  - Experimental and MRI evidence suggest that glatiramer acetate's (Copaxone)
      therapeutic effect in multiple sclerosis (MS) could be mediated by anti
      inflammatory GA-reactive Th2 cells that enter the brain, cross-react with myelin
      antigens, and produce bystander suppression. Furthermore, a neuroprotective
      effect, possibly mediated by neurotrophic factors such as BDNF, has been
      suggested based on experimental evidence in animal models, and the observation
      that inflammatory cells can elaborate BDNF. Therefore, we examined BDNF
      production in 73 GA, 13 MBP, and 22 TT-reactive short-term T-cell lines from 12
      MS patients treated with GA. Ten of 73 GA-TCL (14%), 1 of the MBP-TCL (3%), and 2
      of the TT-TCL (9%) produced BDNF levels two standard deviations above the mean
      levels produced by resting TCL. RT-PCR analysis confirmed BDNF expression in some
      GA- and MBP-reactive TCL. The mean BDNF level produced by GA-TCL was
      significantly higher than that for MBP-TCL, or TT-TCL when lines originating from
      the same patients were compared (P=0.033). All 10 high BDNF-producing GA-reactive
      TCL were Th2-biased as determined by the IL-5/IFN-gamma levels ratio. A positive
      correlation was observed between BDNF and IL-5 (Th2 indicator) (P=0.006) but not
      with IFN-gamma Th1 indicator) levels in GA-TCL derived from MS patients during
      but not pre-treatment. We conclude that while BDNF production by T cells is not
      antigen-specific, GA-reactive TCL are more likely to produce BDNF, and to be Th2
      biased.

PMID- 14568127
TI  - Magnetic resonance imaging demonstrates differential atrophy of pontine base and
      tegmentum in Machado-Joseph disease.
AB  - The pons is one of the brain areas demonstrating selective degeneration in
      Machado-Joseph disease (MJD), which is caused by the expansion of a polyglutamine
      stretch in the protein called ataxin-3. Although the resultant pontine atrophy is
      readily recognized by magnetic resonance imaging (MRI), the features and natural
      process of atrophy are not fully understood. To characterize them, we analyzed
      the midsagittal images of the pons obtained by MRI. We found a difference in
      atrophy between the pontine base and tegmentum. The reduced size of the pontine
      tegmentum was prominent early after the onset of clinical symptoms. No overlap
      was seen in the range of the area of pontine tegmentum between MJD and controls.
      The quotient of atrophy of the pontine tegmentum divided by age correlated well
      with the CAG repeat number. In contrast, the area of the pontine base correlated
      negatively with disease duration. Particularly, the size of the pontine base
      remained in the range of controls for a relatively long time after the onset of
      symptoms. These results suggest that the atrophic process is not uniform in the
      pons in MJD and that the different patterns of atrophy may be derived from the
      differential vulnerability in pontine structures.

PMID- 14568128
TI  - Plasma levels of antioxidant vitamins C and E are decreased in vascular
      parkinsonism.
AB  - Oxidative stress is an important mechanism of cell death in Parkinson's disease
      (PD) and brain ischemia. Vitamins C, E and A are important antioxidants and
      deficiency of these agents has been implicated in the mechanisms of
      atherosclerosis. We measured the levels of the above antioxidant vitamins in 44
      patients with PD, 12 patients with vascular parkinsonism (VP), 11 patients with
      other parkinsonism syndromes of various causes and 39 controls. Vitamin A levels
      did not differ between groups. Vitamins C and E were found decreased in VP, while
      they were normal in PD indicating low levels of antioxidant vitamins in VP and
      stressing the necessity of maintaining sufficient dietary intake of these agents
      in the elderly.

PMID- 14568129
TI  - Sustained induction of survival p-AKT and p-ERK signals after transient hypoxia
      in mice spinal cord with G93A mutant human SOD1 protein.
AB  - Expression of survival p-AKT and p-ERK signals was examined by
      immunohistochemistry and Western blotting in the lumbar spinal cord of 12-week
      old presymptomatic mice with human mutant G93A SOD1 gene (transgenic, Tg) and
      their wild-type (Wt) littermates during normoxia, and 0 and 6 h after 2 h of 9%
      hypoxia. During normoxia, a stronger p-AKT signal was detected in the nucleus of
      the motor neurons of Tg animals. At 0 h of recovery from 2 h of hypoxia, both p
      AKT and p-ERK signals were induced at a slightly lower level in Tg (1.1-1.2-fold)
      compared to those of Wt (1.2-1.5-fold) animals. At 6 h of recovery, both p-AKT
      and p-ERK signals were sustained in the lumbar spinal motor neurons of Tg
      animals, while those in Wt animals quickly returned to baseline level. As a
      control, at 6 h of recovery, the hippocampus of Tg animals showed significantly
      sustained p-AKT levels, but not p-ERK levels, compared to Wt. The current results
      suggest that the presence of mutant SOD1 alters survival p-AKT and p-ERK signals,
      possibly to compensate for the acquired gain-of-function of the mutant protein.

PMID- 14568130
TI  - Prospective study of clinical epidemiology of Guillain-Barre syndrome in Harbin,
      China.
AB  - Clinical manifestations, outcomes, prognostic indicators, and clinico
      epidemiological subgroups were described based on the information of 71 patients
      with Guillain-Barre syndrome (GBS), who were identified from a prospective survey
      in Harbin, China during a 1-year period from 1 October 1997 to 30 September 1998.
      GBS diagnoses of the patients were validated by senior neurologists and most
      patients were followed up for 6 months after onset. Antecedent events, mainly
      respiratory infections, were found in 55 (78%) patients during the month before
      onset. The clinical features, like motor weakness as initial symptoms (82%) and
      tendon areflexia or hyporeflexia (100%), are similar to those reported from other
      populations. However, the proportion (70%) of patients reaching to nadir less
      than 7 days after onset was rather high. Intravenous human immunoglobulin and/or
      plasmapheresis were used in 45% of the patients and steroids in 58%. At 6 months
      after onset, 82% of the patients could walk without aid, 46% of the patients had
      no any residual signs. Four (6%) patients died within 1 month due to respiratory
      failure. Three subgroups with different clinico-epidemiological characteristics
      were identified by using cluster analysis. In conclusion, GBS patients in Harbin,
      China were younger, had shorter time to nadir, frequently preceded by a
      respiratory infection, and often treated with steroids. Clinical and
      epidemiological differences of GBS might exist between various populations.

PMID- 14568131
TI  - Glucose metabolic dysfunction in subjects with a clinical dementia rating of 0.5.
AB  - OBJECTIVE: To investigate the cerebral glucose metabolism of subjects who had a
      Clinical Dementia Rating (CDR) of 0.5, we studied 40 subjects whose CDR was 0.5
      and 40 age-matched healthy subjects. METHODS: Cerebral glucose image of each
      subject was obtained by [18F]-2-fluoro-deoxy-D-glucose (FDG) positron emission
      tomography (PET). The anatomically standardized images were produced with
      NEUROSTAT. Then, the two groups were compared with the Statistical Parametric
      Mappings (SPM) 99. RESULTS: A comparison with the SPM 99 revealed that relative
      cerebral glucose metabolism was lower in the posterior cingulate gyri and
      parietal lobules in the CDR 0.5 group than in the healthy subjects group.
      CONCLUSION: These findings are very similar to those in patients with probable
      Alzheimer's disease (AD) and suggest that the majority of subjects with CDR 0.5
      are suffering from very mild AD or at least a prodromal state of AD.

PMID- 14568132
TI  - Evaluation of cortical excitability by motor and phosphene thresholds in
      transcranial magnetic stimulation.
AB  - Motor threshold (MT), as determined by transcranial magnetic stimulation (TMS),
      is used as a parameter of cortex excitability. In TMS with single or repetitive
      pulses, stimulus intensities in general are referred to the individual MT,
      although it is unclear whether MT also reflects the excitability of nonmotor
      cortical areas such as the visual cortex. Visual cortex excitability can be
      assessed by thresholds for eliciting phosphenes (phosphene threshold, PT)
      following TMS over the occipital cortex. The question of a different efficacy of
      TMS pulses in distinct cortical areas was approached by comparing motor and
      phosphene thresholds using single-pulse TMS applied to the primary motor and
      visual cortex. The aim of the study was to clarify, whether MT and PT correlate
      with each other and whether MT possibly serves as a reasonable measure for the
      excitability of the visual cortex. In 32 healthy volunteers, TMS with biphasic
      single pulses was applied over the motor and visual cortex with a figure of eight
      shaped coil connected to a Dantec MagPro stimulator. MT and PT were individually
      measured (percent of maximal stimulator output). Mean PT (61.4+/-11.7%) was
      significantly higher than mean MT (39.4+/-5.9%) (p=0.01). MT and PT did not
      correlate significantly (r=0.29, p>0.1). These findings suggest that the MT does
      not reflect the excitability of the visual cortex. Regarding excitatory effects,
      the efficacy of TMS may be different over the motor and visual cortex, likely
      related to a different excitability of these cortical areas. This should be
      considered in planning and execution of TMS studies of nonmotor cortical areas.

PMID- 14568133
TI  - Autonomic nervous system function in multiple sclerosis.
AB  - Autonomic dysfunction causes significant disability in patients with multiple
      sclerosis (MS). Abnormalities of bladder, bowel and sexual function have been
      well documented in previous studies but cardiovascular and sudomotor autonomic
      changes have been less frequently reported. The present study has documented
      autonomic symptoms and results of cardiovascular and sudomotor autonomic function
      tests in 63 MS patients and correlated these changes with the clinical features
      of MS.Autonomic symptoms were common in MS patients, the most common being
      disorders of micturition, impotence, sudomotor and gastrointestinal disturbances,
      which were associated with increased MS severity. There was no significant
      association between autonomic symptoms and abnormalities of autonomic
      investigations. Abnormalities of one or more autonomic function tests, not
      including those of bladder, gastrointestinal or sexual dysfunction, were present
      in more than one half of the MS patients. Autonomic dysfunction, defined as
      abnormalities in two or more tests, was found in 18% of patients and was
      associated with increased MS severity. Postural hypotension was very uncommon.
      Parasympathetic cardiovascular autonomic abnormalities occurred in 16% of
      patients and were associated with increased MS severity. Sympathetic
      cardiovascular abnormalities were present in 13% of patients and showed no
      significant association with MS severity. The sympathetic skin response(SSR) was
      abnormal in nearly one half of the patients and also showed no significant
      association with MS severity. There was a variable and heterogenous pattern of
      autonomic test abnormalities found in the MS patients, which were of minor
      clinical significance except for postural hypotension. Cardiovascular and
      sudomotor autonomic abnormalities in MS patients are likely to be due to plaques
      distributed throughout the brainstem and spinal cord affecting anatomically
      widespread autonomic regulatory areas and their connections.

PMID- 14568134
TI  - Lazaroid U-74389G attenuates edema in rat brain subjected to post-ischemic
      reperfusion injury.
AB  - The aim of the present study was to determine the potential therapeutic value of
      21-aminosteroid U-74389G, on blood-brain barrier (BBB) breakdown and edema in
      association with the changes in synaptosomal Na(+)/K(+) and Mg(2+)/Ca(2+)-ATPase
      activities in rat brain subjected to post-ischemic reperfusion injury. Brain
      ischemia was achieved by means of four-vessel occlusion model for 25 min and
      animals were sacrificed after 12 h reperfusion. An increase of cerebral tissue
      water content, blood-brain disruption and the changes of synaptosomal Na(+)/K(+)
      and Mg(2+)/Ca(2+)-ATPases activities were evaluated. U-74389G was given
      intraperitoneally at two times as 5 mg/kg at 10 min prior to ischemia and at the
      beginning of reperfusion. Edema was determined by means of wet-dried weight
      method, and BBB of extravasation of Evan's blue dye. Extravasation of Evan's blue
      dye into brain following ischemia and reperfusion was 2.4-fold of control value
      and brought close to control levels by the effect of U-74389G (p<0.001). Post
      ischemic reperfusion injury caused an increase of 3.7% in tissue water content of
      whole brain and administration of U-74389G lowered the cerebral edema (p<0.001).
      The loses in the Na(+)/K(+)-ATPase and Mg(2+)/Ca(2+)-ATPase activities occurred
      as 42.1% (p<0.01) and 65.7% (p<0.001) of control value, respectively. While
      Mg(2+)/Ca(2+)-ATPase activity was enhanced compared to vehicle-treated group of
      animals (p<0.01), Na(+)/K(+)-ATPase activity was fully recovered when compared to
      control by U-74389G (p>0.05). U-74389G also significantly attenuated neuronal
      necrosis (p<0.001) which was determined in the hippocampal CA1 subfield. Blood
      brain barrier protection, attenuation of brain edema and neuronal necrosis
      concomitant with the stabilizing of membrane-bound enzymes brought about by the
      effect of U-74389G suggest that 21-aminosteroids are worthy of consideration in
      the acute treatment of cerebral ischemia.

PMID- 14568135
TI  - Differential expression and regulation of IL-23 and IL-12 subunits and receptors
      in adult mouse microglia.
AB  - IL-23 and IL-12 are functionally related heterodimeric cytokines that share the
      IL-12p40 subunit. IL-23 and IL-12 function through heterodimeric receptors, which
      share the IL-12Rbeta1 subunit. Production of IL-23, a heterodimer of IL-12p40 and
      IL-23p19, by CNS antigen-presenting cells (APC) is critical for susceptibility to
      experimental autoimmune encephalomyelitis (EAE), the animal model for multiple
      sclerosis (MS). We report that the expression of IL-23p19 mRNA is highly induced
      by stimulation with IFN-gamma and LPS in adult mouse microglia and a microglia
      cell line, EOC13. Expression of the IL-12R subunits, IL-12Rbeta1 and IL-12Rbeta2,
      is upregulated in both microglia and splenic macrophages upon stimulation with
      LPS or IFN-gamma and LPS, whereas the IL-23R subunit is upregulated only in
      macrophages. In EAE, an early peak of IL-23p19 mRNA expression is found in
      CD11b(+) CNS APC, compared with peripheral macrophages. In contrast, IL-12p40 and
      IL-12p35 mRNA maximum levels in the CNS are detected at peak of disease. The
      expression of IL-12p35 mRNA is more sustained than that of IL-12p40 and IL-23p19.
      Thus, IL-23 produced by CNS microglia/macrophages may contribute to the early
      induction of EAE. In the CNS, IL-23 may preferentially target infiltrating
      mononuclear cells, which upregulate IL-23R, rather than parenchymal microglia.

PMID- 14568137
TI  - Posterior interosseous nerve syndrome with hourglass-like fascicular constriction
      of the nerve.
AB  - We describe a case of the posterior interosseous nerve (PIN) syndrome in a
      patient with gout. Exploration of the PIN revealed multiple hourglass-like
      constriction of the PIN, which did not correspond to any extrinsic compressing
      structures. Hourglass-like constrictions of the PIN is one of the causes of the
      painful PIN syndrome.

PMID- 14568136
TI  - Neuroprotective effect of citicoline in 6-hydroxydopamine-lesioned rats and in 6
      hydroxydopamine-treated SH-SY5Y human neuroblastoma cells.
AB  - Citicoline (CDP-choline or cytidine 5'-diphosphocholine) has been used as a
      therapeutic agent in combination with levodopa in the treatment of Parkinson's
      disease (PD). The present study examines the effects of citicoline by using
      validated in vivo and in vitro models. Citicoline reduces the cytotoxic effect of
      6-hydroxydopamine (6-OHDA)-treated human dopaminergic SH-SY5Y neuroblastoma cells
      as measured cellular redox activity with 3-[4.5-dimethylthiazol-2-yl]-2.5
      diphenyltetrazolium bromide (MTT) and increases the levels of reduced glutathione
      (GSH), a major antioxidant agent. Moreover, citicoline (500 mg/kg i.p.)
      administered for 7 days ameliorates functional behaviour by significantly
      reducing the number of apomorphine-induced contralateral rotations in 6-OHDA
      rats. Finally, citicoline significantly attenuates substantia nigra (SN)
      dopaminergic cell dropout and tyrosine hydroxylase immunoreactivity in the
      ipsilateral striatum in rats injected intrastriatally with 6-hydroxydopamine (6
      OHDA).

PMID- 14568138
TI  - Primary intraventricular hemorrhage from dural arteriovenous fistula.
AB  - Dural arteriovenous fistulas (AVFs) cause several types of intracranial
      hemorrhage, but rarely cause primary intraventricular hemorrhage (IVH). We report
      a 67-year-old man with sudden headache and a long history of a pulsatile bruit
      who developed intraventricular hemorrhage without any parenchymal hemorrhage.
      Cerebral angiogram revealed dural arteriovenous fistulas in transverse and
      sigmoid sinuses. Severe retrograde venous drainage seemed to have caused backward
      flow into the subependymal veins with their consequential rupture. Transvenous
      embolization was successful.

PMID- 14568139
TI  - A case of mixed connective tissue disease showing a lymphoid follicle in muscle
      pathology.
AB  - We report a 74-year-old man suffering from mixed connective tissue disease (MCTD)
      accompanied by a lymphoid follicle in muscle pathology. He showed proximal muscle
      weakness and arthritis in finger joints. His laboratory findings were
      characteristic of MCTD. Prednisolone administration favorably improved his
      symptoms. A lymphoid follicle is a rare pathological finding in inflammatory
      myopathies. The immunohistochemical findings suggest that the lymphoid follicle
      would be involved in the specific role for the pathogenesis of MCTD.

PMID- 14568141
TI  - Phylogenetic reconstruction of Gram-positive organisms based on comparative
      sequence analysis of molecular chaperones from the ruminal microorganism
      Ruminococcus flavefaciens FD-1.
AB  - Primers designed on the basis of nucleotide sequences conserved in DnaK and GroEL
      from Gram-positive organisms were used to PCR amplify internal regions of the
      cognate genes from the anaerobic ruminal cellulolytic bacterium Ruminococcus
      flavefaciens FD-1. Genome walking was then utilized to elucidate the remainder of
      the sequences in addition to upstream and downstream regions. The full sequence
      of the gene encoding the GroES protein (groES) was found directly upstream from
      groEL. The deduced amino acid sequence of the groEL gene showed the highest
      homology with the amino acid sequence of the Clostridium thermocellum GroEL
      protein (72% amino acid identity). Similarly, translation of the groES nucleotide
      sequence showed highest homology to the C. thermocellum GroES protein (61% amino
      acid identity). Analysis of the upstream region of this chaperonin operon
      revealed a CIRCE regulatory element 45 bp upstream from the putative start of the
      groES ORF. The deduced amino acid sequence of the putative dnaK gene showed the
      highest homology with the amino acid sequence of the Clostridium acetobutylicum
      DnaK protein (68% amino acid identity). Phylogenetic analyses based on the
      translated sequences reiterate this relationship between R. flavefaciens and the
      Clostridia. However, when the nucleotide sequences of Gram-positive organisms are
      analyzed, a different topology occurs of the relationship between high- and low
      G+C Gram-positive organisms to the 16S rRNA interpretation.

PMID- 14568142
TI  - Two phenotypically compensating isocitrate dehydrogenases in Ralstonia eutropha.
AB  - The tricarboxylic acid (TCA) cycle enzyme isocitrate dehydrogenase (IDH) and the
      glyoxylate bypass enzyme isocitrate lyase are involved in catabolism of
      isocitrate and play a key role in controlling the metabolic flux between the TCA
      cycle and the glyoxylate shunt. Two IDH genes icd1 and icd2 of Ralstonia eutropha
      HF39, encoding isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2
      (IDH2), were identified and characterized. Icd1 was functionally expressed in
      Escherichia coli, whereas icd2 was expressed in E. coli but no activity was
      obtained. Interposon-mutants of icd1 (HF39Deltaicd1) and icd2 (HF39Deltaicd2) of
      R. eutropha HF39 were constructed and their phenotypes were investigated.
      HF39Deltaicd1 retained 43% of IDH activity, which was not induced by acetate, and
      HF39Deltaicd2 expressed 74% of acetate-induced IDH activity. Both
      HF39Deltaicd1and HF39Deltaicd2 kept the same growth rate on acetate as the wild
      type. These data suggested that IDH1 is induced by acetate. The interposon
      mutants HF39Deltaicd1 and HF39Deltaicd2 accumulated the same amount of poly(3
      hydroxybutyric acid) as the wild-type.

PMID- 14568143
TI  - Filling a gap in the central metabolism of archaea: prediction of a novel
      aconitase by comparative-genomic analysis.
AB  - Aconitase, an essential enzyme of the tricarboxylic acid cycle (TCA), so far has
      been identified only in a minority of archaeal genomes. This enzyme belongs to
      the aconitase A family, which is represented in most bacteria and eukaryotes.
      Using iterative sequence database search, we linked two previously
      uncharacterized protein families (COG1679 and COG1786), respectively, to the
      three Fe-S-cluster-associated aconitase domains and the swiveling domain, the
      four domains that are present in all known aconitase families. The respective
      genes are often found in one predicted operon and, moreover, are fused in several
      species, suggesting a functional and physical interaction. We predict that these
      proteins together comprise a previously undetected, distinct aconitase family,
      which we designated aconitase X. Aconitase X is encoded in the genomes of many
      archaea and some proteobacteria. Among archaea, the pattern of aconitase X
      occurrence complements that of aconitase A such that together the two enzymes
      account for aconitase activity in all archaea. Phylogenetic analysis indicates
      that aconitase X is likely to be the ancestral archaeal form, with non
      orthologous displacement in some of the archaea apparently brought about by
      horizontal transfer of the gene for bacterial aconitase A. The prediction of
      aconitase X completes the TCA cycle for Methanothermobacter thermoautotrophicus
      and Archaeoglobus fulgidus and suggests that most archaea have a full TCA cycle.

PMID- 14568144
TI  - Expression of Streptococcus pneumoniae antigens, PsaA (pneumococcal surface
      antigen A) and PspA (pneumococcal surface protein A) by Lactobacillus casei.
AB  - A number of recent research works in lactic acid bacteria aim towards the design
      of new strains that could be used as live vectors for the delivery of antigens
      for oral vaccination, or other therapeutic molecules. In this work, an inducible
      expression system based on the Lactobacillus casei lactose operon promoter was
      used to express three important surface antigens of Streptococcus pneumoniae in
      this lactic acid bacterium: a virulence-related pneumococcal surface antigen
      (PsaA) and two variants of the virulence factor PspA (pneumococcal surface
      protein A). Expression of the three proteins was induced upon growth on lactose
      and strongly repressed by glucose. These proteins were produced intracellularly.
      Also, secretion to the growth medium was achieved by means of a fusion to the
      secreting and processing signals from the L. casei surface proteinase.
      Interestingly, while secreted PspA proteins were found in the culture
      supernatants, PsaA remained trapped in the cell wall. Expression of pneumococcal
      antigens in a food-grade organism opens an alternative for mucosal vaccination
      against this important pathogen.

PMID- 14568145
TI  - Specificity of the second binding protein of the peptide ABC-transporter (Dpp) of
      Lactococcus lactis IL1403.
AB  - The genome sequence of Lactococcus lactis IL1403 revealed the presence of a
      putative peptide-binding protein-dependent ABC-transporter (Dpp). The genes for
      two peptide-binding proteins (dppA and dppP) precede the membrane components,
      which include two transmembrane protein genes (dppB and dppC) and two ATP-binding
      protein genes (dppD and dppF). In this work, the gene specifying the second
      peptide-binding protein (DppP) was cloned under the control of the nisin
      promoter. The protein fused to a carboxyl-terminal histidine tag (DppP-His(6))
      was purified and its binding properties were determined by monitoring the
      intrinsic fluorescence changes observed upon ligand binding. The major features
      of peptide binding to DppP-His(6) include: (i) a requirement for a free N
      terminal alpha-amino group in the ligand; (ii) a high affinity for di-, tri- and
      tetra-peptides; (iii) affinity constants for peptide binding independent of pH;
      and (iv) a high affinity for D-isomer-containing peptides. Remarkably, the
      features (ii), (iii) and (iv) differ from those previously reported for DppA
      His(6), suggesting that DppP-His(6) is a more versatile peptide-binding protein
      that could have additional functions.

PMID- 14568146
TI  - Regulation of the glutamate-dependent acid-resistance system of diarrheagenic
      Escherichia coli strains.
AB  - The ability to withstand an acid challenge of pH 2.5 or less by Escherichia coli
      strains is a trait generally believed to be restricted to their stationary phase
      of growth. Of the three distinct acid-resistance systems that have been
      identified in E. coli, the glutamate-dependent acid resistance (GAD) system
      provides the highest level of acid resistance. Earlier reports indicated that in
      the exponential growth phase of E. coli K-12 strains the GAD system is not
      active. The present study reports that when grown on minimal medium several
      diarrheagenic and K-12 strains of E. coli have a complete set of induced genes
      necessary for GAD in the exponential growth phase to overcome the acid challenge
      of pH 2.5 for several hours. A previously identified factor(s) specific to the
      GAD system in the stationary phase and predicted to undergo dilution during the
      exponential phase appears to be glutamate-decarboxylase isozyme(s) inactivated
      differentially in the rich vs. minimal growth media.

PMID- 14568147
TI  - The autolytic activity of the recombinant amidase of Staphylococcus saprophyticus
      is inhibited by its own recombinant GW repeats.
AB  - The Aas (autolysin/adhesin of Staphylococcus saprophyticus) is a multifunctional
      surface protein containing two enzymatic domains an N-acetyl-muramyl-L-alanine
      amidase, an endo-beta-N-acetyl-D-glucosaminidase, and two different regions of
      repetitive sequences, an N-terminal and a C-terminal repetitive domain. The C
      terminal repetitive domain is built up by the repeats R1, R2 and R3, which
      interconnect the putative active centers of the amidase and glucosaminidase. To
      investigate the influence of the C-terminal repeats and the N-terminal repeats on
      the amidase activity, the repetitive domains and fragments of them were cloned
      and expressed in Escherichia coli. The influence of the different fragments on
      the activity of the recombinant amidase of the Aas, consisting of the active
      center of the enzyme and repeat R1, was investigated in a turbidimetric
      microassay. The different fragments derived from the C-terminal repeats inhibited
      the amidase activity, while the N-terminal repeats did not influence the activity
      of the enzyme. The inhibiting activity increased with the number of GW repeats
      the recombinant fragment contained. Thus we conclude, that the C-terminal GW
      repeats and not the N-terminal repeats are necessary for the cell wall targeting
      and the autolytic function of the amidase.

PMID- 14568148
TI  - mymA operon of Mycobacterium tuberculosis: its regulation and importance in the
      cell envelope.
AB  - Mycobacterium tuberculosis faces various stressful conditions inside the host and
      responds to them through a coordinated regulation of gene expression. We had
      previously reported identification of the virS gene of M. tuberculosis (Rv3082c)
      belonging to the AraC family of transcriptional regulators. In the current study,
      we show that the seven genes (Rv3083-Rv3089) which are present divergently to
      virS (Rv3082c) constitute an operon designated the mymA operon. Further
      investigation on the regulation of this operon showed that transcription of the
      mymA operon is dependent on the presence of VirS protein. A four-fold induction
      of the mymA operon promoter occurs specifically in wild-type M. tuberculosis and
      not in the virS mutant of M. tuberculosis (MtbDeltavirS) when exposed to acidic
      pH. Expression of the mymA operon was also induced in infected macrophages by 10
      fold over a 6-day period. To gain an insight into the function of the proteins
      encoded by this operon, we carried out a bioinformatic analysis, which suggested
      the involvement of these proteins in the modification of fatty acids required for
      cell envelope. This was supported by altered colony morphology and cell envelope
      structure displayed by the virS mutant of M. tuberculosis (MtbDeltavirS).

PMID- 14568149
TI  - Ion motive force dependence of protease secretion and phage transduction in
      Vibrio cholerae and Pseudomonas aeruginosa.
AB  - Vibrio cholerae is known to secrete a large number of proteins into the
      extracellular milieu, including the important virulence factor cholera toxin
      (CT). However, one of the most abundant proteins found in V. cholerae
      supernatants is the zinc-metalloprotease HA/protease (HAP). Whereas efficient
      protein secretion in Escherichia coli requires ATP hydrolysis and the proton
      motive force (pmf), little is known about the energy requirements for protein
      secretion in V. cholerae. To analyze some of the energy requirements for protein
      secretion in V. cholerae, HAP accumulation in culture supernatants following
      growth in the presence of various ionophores was assayed. Extracellular
      production of HAP was strongly reduced in the presence of monensin, an artificial
      Na(+)/H(+) antiporter that collapses the DeltapNa(+) across the membrane without
      affecting Deltapsi, whereas the protonophore CCCP had no significant effect on
      the extracellular accumulation of HAP. In contrast, extracellular protease
      production in Pseudomonas aeruginosa was affected by CCCP, but not monensin.
      Furthermore, extracellular protease production of V. cholerae, but not P.
      aeruginosa, was increased in increasing amounts of NaCl in the culture medium.
      Together these results indicate that the V. cholerae HAP requires an intact
      sodium motive force (smf) for its efficient translocation across the membranes,
      whereas extracellular protease production by P. aeruginosa requires only pmf. As
      the entry of some bacteriophage genomes has been reported to require pmf, the
      effects of ionophores on the efficiency of tranduction of V. cholerae by the
      CTXPhi phage were analyzed. CTXPhi transduction was strongly affected by CCCP,
      but not monensin, suggesting that phage entry requires pmf but not smf.
      Understanding the energy requirements for these potentially important virulence
      aspects of pathogens might lead to novel intervention strategies.

PMID- 14568150
TI  - Characterization of human humoral responses to the major outer membrane protein
      and OMP2 of Chlamydophila pneumoniae.
AB  - Chlamydophila pneumoniae infection is associated with a range of diseases
      including pneumonia, asthma and heart disease. Although an obligate intracellular
      pathogen, high levels of antigen-specific antibody are induced and serology is
      frequently used to diagnose these infections. Proteins targeted by the humoral
      response include the major outer membrane protein (MOMP) and outer membrane
      protein 2 (OMP2). Using human anti-chlamydial sera we have defined the B cell
      epitopes recognized on MOMP and OMP2. Peptides from MOMP, unlike OMP2, were not
      strongly recognized. Two of these epitopes when linked to an inert carrier
      reacted strongly with high-titer anti-C. pneumoniae sera.

PMID- 14568151
TI  - Megaplasmids in Gram-negative, moderately halophilic bacteria.
AB  - We have discovered that many Halomonas species harbour large extrachromosomal DNA
      elements. Using currently available protocols it is technically very difficult to
      identify large plasmids in bacteria, and even more so when they are coated in
      mucous polysaccharide. We used culture conditions suitable for both halophilic
      and halophilic exopolysaccharide-producing bacteria and applied a modified gel
      electrophoresis method to locate and visualise the megaplasmids. Almost all the
      species of Halomonas studied harbour two plasmids of about 70 kb and 600 kb and
      some species carry other smaller extrachromosomal DNA elements. The common
      presence of these megaplasmids may well be related to the survival strategies of
      the bacteria in their special surroundings.

PMID- 14568152
TI  - A generalized transducing thiophage (TPC-1) of a facultative sulfur
      chemolithotrophic bacterium, Bosea thiooxidans CT5, of alpha-Proteobacteria,
      isolated from Indian soil.
AB  - We have isolated and characterized a double-stranded DNA bacteriophage (TPC-1) of
      Bosea thiooxidans, a facultative sulfur chemolithotrophic bacterium. The name
      'thiophage' is introduced for phage(s) infecting sulfur chemolithotrophic
      bacteria. Electron micrographs showed the phage particle with an icosahedral head
      and a very short wedge-like tail. TPC-1 is classified as the C1 morphotype of the
      Podoviridae family. Restriction map and terminal ends detection by end fill
      labeling of the TPC-1 genomic DNA showed that the genome is linear with 5'
      protruding cohesive termini. Contour length mapping of the DNA genome also
      revealed it to be a linear fragment with size ( approximately 44 kb)
      corresponding with the size estimated from restriction fragment analyses and
      proved the non-redundant nature of the linear genome topology. In colorless
      sulfur chemolithotrophic microorganisms, TPC-1 is the first report of a
      generalized transducing thiophage.

PMID- 14568153
TI  - Cystine uptake prevents production of hydrogen peroxide by Lactobacillus
      fermentum BR11.
AB  - BspA is an abundant surface protein from Lactobacillus fermentum BR11, and is
      required for normal cystine uptake. In previous studies, a mutant strain
      deficient in BspA (L. fermentum PNG201) was found to be sensitive to oxidative
      stress. In this study, the biochemical basis for this was explored. It was found
      that under aerobic batch culture conditions in de Mann-Rogosa-Sharpe medium, both
      L. fermentum BR11 and PNG201 entered stationary phase due to hydrogen peroxide
      accumulation. However, this took place at a lower optical density for PNG201 than
      for BR11. Measurements of hydrogen peroxide levels revealed that the BspA mutant
      strain overproduces this compound. Addition of 6 mM cystine to aerobic cultures
      was found to prevent hydrogen peroxide production by both the BR11 and PNG201
      strains, but lower cystine concentrations depressed hydrogen peroxide production
      in BR11 more efficiently than in PNG201. Each mole of cystine was able to prevent
      the production of several moles of hydrogen peroxide by L. fermentum BR11,
      suggesting that hydrogen peroxide breakdown is dependent upon a thiol that cycles
      between reduced and oxidized states. It was concluded that peroxide breakdown by
      L. fermentum BR11 is dependent upon exogenous cystine. It is most probable that
      the imported L-cystine is catabolized by a cystathionine lyase and then converted
      into a thiol reductant for a peroxidase.

PMID- 14568154
TI  - Isolation of Brachymonas petroleovorans CHX, a novel cyclohexane-degrading beta
      proteobacterium.
AB  - A new bacterium that grows aerobically on cyclohexane was isolated from the
      wastewater plant of a petroleum refinery. This strain grows on a range of light
      hydrocarbons (C5-C10) as well as on some aromatic compounds such as toluene and m
      cresol. Growth on hydrocarbons requires the presence of yeast extract and other
      complex media components that are not substrates for growth themselves. Strain
      CHX is resistant to cyclohexane and grows at concentrations up to 2 g l(-1).
      Strain CHX branches deeply within the Comamonadeae family of beta-proteobacteria
      and is tentatively assigned to the Brachymonas genus as Brachymonas
      petroleovorans CHX.

PMID- 14568155
TI  - Testing the nematophagous biological control strain Paecilomyces lilacinus 251
      for paecilotoxin production.
AB  - Paecilomyces lilacinus is a nematophagous fungus currently developed as a
      biological control agent. In order to evaluate potential toxin production,
      culture extract and concentrated culture supernatant of P. lilacinus strain 251
      were tested against Gram-negative and Gram-positive bacteria. High-performance
      liquid chromatography analysis was carried out to compare the chromatograms of P.
      lilacinus strain 251 with the chromatogram of known paecilotoxin. It was found
      that the 251 strain of P. lilacinus did not produce detectable levels of
      paecilotoxin or other toxins with antimicrobial activity.

PMID- 14568157
TI  - Purification and characterization of laccase from the rice blast fungus,
      Magnaporthe grisea.
AB  - A 70-kDa extracellular laccase was purified from the rice blast fungus
      Magnaporthe grisea using gel filtration and ion exchange chromatography The
      procedure provided 282-fold purification with a specific enzyme activity of
      225.91 U mg(-1) and a yield of 11.92%. The enzyme oxidized a wide range of
      substrates. The highest level of oxidation was detected with syringaldazine as
      the substrate. Using syringaldazine as the substrate, the enzyme exhibited a pH
      optimum of 6 and temperature optimum of 30 degrees C, and its K(m) was 0.118 mM.
      The enzyme was strongly inhibited by Cu-chelating agents.

PMID- 14568156
TI  - Identification of genes involved in the switch between the smooth and rugose
      phenotypes of Vibrio cholerae.
AB  - Vibrio cholerae can switch to a 'rugose' phenotype characterized by an
      exopolysaccharide (EPS) matrix, wrinkled colony morphology, increased biofilm
      formation and increased survival under specific conditions. The vps gene cluster
      responsible for the biosynthesis of the rugose EPS (rEPS) is positively regulated
      by VpsR. We recently identified media (APW#3) promoting EPS production and the
      rugose phenotype and found epidemic strains switch at a higher frequency than non
      pathogenic strains, suggesting this switch and the rugose phenotype are important
      in cholera epidemiology. In this study, transposon mutagenesis on a smooth V.
      cholerae strain was used to identify mutants that were unable to shift to the
      rugose phenotype under inducing conditions to better understand the molecular
      basis of the switch. We identified vpsR, galE and vps previously associated with
      the rugose phenotype, and also identified genes not previously associated with
      the phenotype, including rfbD and rfbE having roles in LPS (lipopolysaccharide)
      synthesis and aroB and aroK with roles in aromatic amino acid synthesis.
      Additionally, a mutation in amiB encoding N-acetylmuramoyl-L-alanine amidase
      caused defects in the switch, motility and cell morphology. We also found that a
      gene encoding a novel regulatory protein we termed RocS (regulation of cell
      signaling) containing a GGDEF and EAL domains and associated with c-di-GMP levels
      is important for the rugose phenotype, EPS, biofilm formation and motility. We
      propose that modulation of cyclic dinucleotide (e.g. c-di-GMP) levels might have
      application in regulating various phenotypes of prokaryotes. Our study shows the
      molecular complexity of the switch between the smooth and rugose phenotypes of V.
      cholerae and may be relevant to similar phenotypes in other species.

PMID- 14568158
TI  - Production, survival and efficacy of Coniothyrium minitans conidia produced in
      shaken liquid culture.
AB  - Coniothyrium minitans is a fungal biocontrol agent of the plant pathogen
      Sclerotinia sclerotiorum. Growth and sporulation of 21 strains of C. minitans
      were examined on potato dextrose agar (PDA) and compared with that in potato
      dextrose broth (PDB) in shaken culture after 12 days at 20 degrees C, to identify
      strains with potential for inoculum production in liquid culture. Four strains
      that produced high numbers of pycnidia in PDA also formed pycnidia on mycelial
      strands in PDB and 10(7) conidia ml(-1) broth were produced. The other strains
      formed pellets during shaking, resulting in production of less than 10(5) conidia
      ml(-1). Conidia from shaken PDB culture had the same ability to infect and rot
      sclerotia of S. sclerotiorum as conidia produced routinely on PDA, and survived
      well in dry kaolin dust for 6 months at temperatures less than 8 degrees C with
      less than 1 log(10) colony forming units mg(-1) loss. These results suggest that
      it might be possible to identify useful strains of C. minitans for future
      commercial conidial production in liquid fermentation systems based on
      morphological characteristics on agar.

PMID- 14568159
TI  - The number and organization of the rRNA genes of several strains of Mycobacterium
      simiae.
AB  - The type strain of Mycobacterium simiae and four Cuban strains, each representing
      a group of variants sharing a characteristic pattern of glycopeptidolipids, were
      investigated. Each of the five strains was found to have a single rRNA (rrn)
      operon per genome. Each rrn operon was found to be located downstream from murA.
      Unusually for slow-growing mycobacteria, three transcription start points were
      identified for each operon. Gene sequences were established extending from near
      to the 3'-ends of murA, the intergenic regions and the 5'-ends of the 16S rDNAs.
      Characteristic strain differences were identified.

PMID- 14568161
TI  - Characterisation of preYvaY export reveals differences in the substrate
      specificities of Bacillus subtilis and Escherichia coli leader peptidases.
AB  - Translocation, processing and secretion of YvaY, a Bacillus subtilis protein of
      unknown function, were characterised both in B. subtilis and in Escherichia coli.
      In its natural host B. subtilis, YvaY was transiently synthesised at the end of
      the exponential growth phase. It was efficiently secreted into the culture
      supernatant in spite of a calculated membrane spanning domain in the mature part
      of the protein. In E. coli, despite the high conservation of Sec-dependent
      transport components, processing of preYvaY was strongly impaired. To uncover
      which elements of E. coli and B. subtilis translocation systems are responsible
      for the observed substrate specificity, components of the B. subtilis Sec-system
      were co-expressed besides yvaY in E. coli. Expression of B. subtilis secA or
      secYEG genes did not affect processing, but expression of B. subtilis signal
      peptidase genes significantly enhanced processing of preYvaY in E. coli. While
      the major signal peptidases SipS or SipT had a strong stimulatory effect on
      preYvaY processing, the minor signal peptidases SipU, SipV or SipW had a far less
      stimulatory effect in E. coli. These results reveal that targeting and
      translocation of preYvaY is mediated by the E. coli Sec proteins but processing
      of preYvaY is not performed by E. coli signal peptidase LepB. Thus, differences
      in substrate specificities of E. coli LepB and the B. subtilis Sip proteins
      provide the bottleneck for export of YvaY in E. coli. Significant slower
      processing of preYvaY in absence of SecB indicated that SecB mediates targeting
      of the B. subtilis precursor.

PMID- 14568160
TI  - Apparent growth phase-dependent phosphorylation of malonyl coenzyme A:acyl
      carrier protein transacylase (MCAT), a major fatty acid synthase II component in
      Mycobacterium bovis BCG.
AB  - Probing protein extracts from exponentially growing and stationary phase cultures
      of Mycobacterium bovis BCG with anti-phospho amino acid antibodies revealed a 31
      kDa anti-phospho threonine antibody-reactive protein specific to growing culture.
      The corresponding protein was purified via two-dimensional gel electrophoresis
      and identified via mass spectrometry to be malonyl coenzyme A:acyl carrier
      protein transacylase (MCAT), a component of the fatty acid biosynthetic pathway.
      MCAT tagged with histidine reacted with anti-phospho threonine antibody and was
      positive in an in-gel chemical assay for phospho proteins. Analysis of the growth
      phase dependence of MCAT-His phosphorylation and protein levels showed that
      phosphorylated MCAT-His can be detected only in growing culture. In contrast,
      MCAT-His protein level was growth phase-independent. These results suggest that
      MCAT may be a substrate of a protein kinase and phosphatase, and that aspects of
      fatty acid synthesis in tubercle bacilli are regulated by protein
      phosphorylation.

PMID- 14568162
TI  - Allelic diversity in the host genetic background may be an important determinant
      in tumor metastatic dissemination.
AB  - Metastasis, the spread and growth of tumors at secondary sites, is an extremely
      important clinical event, since the majority of cancer mortality is associated
      with the metastatic tumors rather than the primary tumor. In spite of the
      importance of metastasis in the clinical setting, the actual process is extremely
      inefficient. Millions of tumor cells can be shed into the vasculature daily yet
      few secondary tumors are formed. To successfully colonize a distant site tumor
      cells must overcome a series of barriers. Failure to complete any single step in
      the metastatic cascade abrogates the ability to form a secondary lesion. A
      variety of theories have been proposed to explain the inefficiency of the
      metastatic process. The most commonly accepted, the progression theory, posits a
      series of random mutational occurs within a primary tumor to generate a small
      subpopulation that acquires full metastatic capability. While significant
      evidence supports this model, recent discoveries demonstrating the ability to
      predict metastatic propensity from gene expression profiles in bulk tumor tissue
      are not consistent with only a small subpopulation of cells in the primary tumor
      acquiring metastatic ability. A second theory of metastatic inefficiency, the
      transient compartment theory, is more consistent with the microarray data, but
      does not completely explain observations like metastasis associated loss-of
      heterozygosity events. To reconcile the observed results additional variables
      need to be added to the model of metastatic inefficiency. One possible variable
      that might explain the discrepancies is genetic background effects. Studies have
      demonstrated that the genetic background a tumor arises on can have significant
      affects on the ability of the tumor to metastasize and on gene expression
      profiles. Thus the observations could be reconciled by combining the theories,
      with genetic background influencing both metastatic efficiency and predictive
      gene expression profiles, upon which subsequently occur metastasis-promoting
      mutational and epigenetic events. If the genetic background is an important
      determinant of metastatic efficiency it would have significant implications for
      the clinical prediction and treatment of metastatic disease, as well as for the
      design of potential prevention strategies.

PMID- 14568163
TI  - The effects of parathyroid hormone fragments on bone formation and their lack of
      effects on the initiation of colon carcinogenesis in rats as indicated by
      preneoplastic aberrant crypt formation.
AB  - The parathyroid hormone (PTH) and some of its fragments and analogs stimulate
      bone growth in various animal models and humans and one of them (hPTH-(1-34)) has
      been approved by the USFDA for treating osteoporosis. However, there are reports
      that PTH can stimulate the PI-3 kinase/mitogen-activated protein kinases-mediated
      proliferation of rat enterocytes and that primary hyperparathyroidism in humans
      is associated with an increased incidence of colon cancer. Here we have
      investigated the ability of two PTH fragments, hPTH-(1-34)NH(2) and
      [Leu(27)]cyclo(Glu(22)-Lys(26))hPTH-(1-31)NH(2) to initiate colon carcinogenesis
      or increase the initiatory activity of the widely used colon carcinogen
      azoxymethane (AOM). The initiation of colon carcinogenesis by AOM was indicated
      by the very early appearance of aberrant crypt foci. While both PTH peptides
      strongly stimulated femoral bone formation, they did not cause the appearance of
      ACFs or affect the number or the distribution along the colon of AOM-induced
      ACFs. Nor did AOM affect the PTHs' ability to stimulate bone formation. Thus, a
      relatively short PTH treatment that is long enough to strongly stimulate bone
      formation does not initiate colon carcinogenesis in rats.

PMID- 14568164
TI  - Shikonin modulates cell proliferation by inhibiting epidermal growth factor
      receptor signaling in human epidermoid carcinoma cells.
AB  - Shikonin isolated from the roots of the Chinese herb Lithospermum erythrorhizon
      has been associated with anti-inflammatory properties. We evaluated shikonin's
      chemotherapeutic potential and investigated its possible mechanism of action in a
      human cutaneous neoplasm in tissue culture. Shikonin preferentially inhibits the
      growth of human epidermoid carcinoma cells concentration- and time-dependently
      compared to SV-40 transfected keratinocytes, demonstrating its anti-proliferative
      effects against this cancer cell line. Additionally, shikonin decreased
      phosphorylated levels of EGFR, ERK1/2 and protein tyrosine kinases, while
      increasing phosphorylated JNK1/2 levels. Overall, shikonin treatment was
      associated with increased intracellular levels of phosphorylated apoptosis
      related proteins, and decreased levels of proteins associated with proliferation
      in human epidermoid carcinoma cells.

PMID- 14568165
TI  - Protoporphyrin IX production and its photodynamic effects on glioma cells,
      neuroblastoma cells and normal cerebellar granule cells in vitro with 5
      aminolevulinic acid and its hexylester.
AB  - 5-Aminolevulinic acid (ALA) has shown promising in photodynamic detection and
      therapy of brain tumor. However, the knowledge on selective accumulation of ALA
      induced protoporphyrin IX (PpIX) in brain tumor tissue is still fragment. In the
      present study, the rat C6 glioma cells, human SK-N-SH neuroblastoma cells, and
      rat normal cerebellar granule cells (RCG) were used to investigate the PpIX
      production and photocytotoxicity in vitro. The C6 cells and SK-N-SH cells showed
      a similar kinetics of PpIX accumulation after exposure to ALA or ALA hexyl ester
      (ALA-H), with an initial increase up to 6-8 h and then saturated. In the case of
      RCG cells, the PpIX accumulation slowly increased until 12 h studied. However the
      cellular PpIX content was more than 10 times higher in the C6 and SK-N-SH cells
      than that in the normal RCG cells. The intracellular localization of PpIX
      measured by cofocal laser scanning microscopy was in same pattern in the C6
      glioma cells and RCG normal cells with a diffuse cytoplasm distribution. The
      sensitivity of the C6 cells and SK-N-SH cells to ALA or ALA-H PDT was similar. It
      appears that ALA-H could achieve similar or slightly better results than ALA with
      respect to PpIX production and photoinactivation of cells, although a 10 times
      lower concentration of ALA-H was used.

PMID- 14568166
TI  - Lack of significant inhibitory effects of a plant lignan tracheloside on 2-amino
      1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced mammary carcinogenesis in
      female Sprague-Dawley rats.
AB  - Tracheloside, one of the plant lignans which can be extracted from the debris
      after safflower oil is produced from the seeds of Carthamus tinctorious, is an
      analogue of another plant lignan, arctiin, the side-chain C-2 of the five
      membered ring being changed from a hydrogen to a hydroxyl group. We have already
      demonstrated that arctiin has chemopreventive effect on mammary carcinogenesis.
      Therefore, chemopreventive effects of tracheloside on the initiation or post
      initiation period of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)
      induced mammary carcinogenesis in female rats were examined. For initiation,
      female Sprague-Dawley (SD) rats at the 6 weeks of age were given intragastric
      administrations of 100 mg/kg body weight of PhIP once a week for 8 weeks. The
      animals were treated with 0.2 or 0.02% tracheloside during or after this
      carcinogen exposure. Control rats were fed basal diet with PhIP initiation or
      0.2% tracheloside or basal diet alone without initiation throughout the
      experimental period. All surviving animals were necropsied at the week 52 of
      administration. There were no clear treatment-related changes with statistical
      significance in all parameters for mammary carcinomas measured in this
      experiment. These results indicate that tracheloside may not exert significant
      effects on PhIP-induced mammary carcinogenesis at least under the present
      experiment condition.

PMID- 14568167
TI  - Associations between prostate cancer susceptibility and parameters of exposure to
      ultraviolet radiation.
AB  - Low sunlight exposure confers increased prostate cancer risk. In a study
      conducted in northern England, we investigated how combinations of exposure
      measures affect this risk. Recursive partitioning was used to identify
      combinations of exposure parameters that distinguished 453 prostate cancers from
      312 benign hypertrophy patients. Sunbathing score most significantly defined
      cancer patients; 78.7% men with low scores (</=3.0) and 40.2% men with high
      scores (>8.0) had cancer. These subgroups were stratified by childhood
      sunburning, holidays in a hot climate and skin type such that subgroups with a
      13.0-fold increased risk of cancer were identified.

PMID- 14568168
TI  - Contribution of the CHEK2 1100delC variant to risk of multiple colorectal adenoma
      and carcinoma.
AB  - Aneuploidy is a characteristic of a subset of colorectal tumours. CHEK2 (also
      known as CHK2) is one of the cell cycle checkpoint genes coding for a family of
      proteins that sense damage in eukaryotic cells. Germline variation in CHEK2 has
      recently been shown to confer cancer susceptibility. Heterozygous mutations have
      been identified in patients with TP53-negative Li-Fraumeni syndrome. Furthermore,
      the CHEK2 1100delC variant carried by 1% of the population has been shown to act
      as a low penetrance allele for both breast and prostate cancers. To further our
      knowledge about the contribution of CHEK2 1100delC to cancer incidence we have
      analysed a series of 149 patients with multiple colorectal adenomas some of whom
      developed colorectal cancer. The CHEK2 1100delC allele was not over-represented
      in cases suggesting that this variant is not associated with an increased risk of
      colorectal disease.

PMID- 14568169
TI  - Reduced protein degradation rates and low expression of proteolytic systems
      support skeletal muscle hypertrophy in transgenic mice overexpressing the c-ski
      oncogene.
AB  - We have investigated the protein turnover modulations involved in the
      hypertrophic muscle phenotype of c-ski overexpressing transgenic mice. In these
      animals, the body weight is increased and all the muscles examined show a
      definite hypertrophy. The protein degradation rate is significantly reduced in
      the fast twitch muscles of c-ski transgenic animals with respect to controls; in
      contrast, there are no detectable differences in the synthesis rates. The down
      regulation of protein breakdown is paralleled by decreased expression of genes
      belonging to the lysosomal as well as to the ATP-ubiquitin-dependent proteolytic
      pathways.

PMID- 14568170
TI  - 14-3-3 sigma possibly plays a constitutive role in papillary carcinoma, but not
      in follicular tumor of the thyroid.
AB  - 14-3-3 sigma is a negative regulator of the cell cycle and contributes to G2
      arrest. Thus far, the lack of its expression due to hypermethylation of the CpG
      islands has been reported in some carcinomas. In this study, we investigated the
      expression of 14-3-3 sigma in thyroid neoplasms by means of immunohistochemistry
      as well as Western blot analysis. Normal follicules did not express 14-3-3 sigma.
      In 82 papillary carcinomas, all the cases expressed 14-3-3 sigma and its
      expression was not reduced but even enhanced in the advanced stage and in poorly
      differentiated types. Furthermore, 21 of the 23 anaplastic carcinomas expressed
      14-3-3 sigma and its expression level tended to be higher than in papillary
      carcinoma. On the other hand, none of the 34 follicular carcinomas or 29
      follicular adenomas expressed 14-3-3 sigma. These results suggest that 14-3-3
      sigma plays a constitutive role in papillary carcinoma rather than acting as a
      cell cycle regulator, whereas it is not required for the occurrence and
      development of follicular tumor.

PMID- 14568171
TI  - Expression of alpha1,6-fucosyltransferase (FUT8) in papillary carcinoma of the
      thyroid: its linkage to biological aggressiveness and anaplastic transformation.
AB  - Previous studies have demonstrated that terminal fucosylation is associated with
      the biological aggressiveness of carcinomas, but the significance of core
      fucosylation (alpha1,6-fucosylation) through alpha1,6-fucosyltransferase (FUT8)
      has not been studied in depth. Herein, we investigated the expression of alpha1,6
      fucosyltransferase (FUT8) in 133 cases of thyroid carcinomas using an
      immunohistochemical approach. The expression of FUT8 was quite low in normal
      follicules. A high expression of FUT8 was observed in 33.3% of papillary
      carcinoma and the incidence was directly linked to tumor size and lymph node
      metastasis. In contrast, this phenomenon was less frequently observed in
      follicular carcinoma and anaplastic (undifferentiated) carcinoma. These results
      suggest that FUT8 expression may be a key factor in the progression of thyroid
      papillary carcinomas, but not follicular carcinomas, and decreases in FUT8
      expression might be linked to anaplastic transformation.

PMID- 14568172
TI  - Platelet-derived endothelial cell growth factor predicts of progression and
      recurrence in primary epithelial ovarian cancer.
AB  - We investigated the clinical significance of platelet-derived endothelial cell
      growth factor (PD-ECGF) as measured by enzyme-linked immunosorbent assay in
      primary epithelial ovarian cancers (EOC), finding amounts to be significantly
      greater in cancers than in normal ovarian tissue (p<0.01). PD-ECGF was
      significantly more abundant in stages III and IV than in lower stages (p<0.05),
      and also was high in tumors with macroscopically evident metastases in the
      peritoneal cavity (p<0.05), or pelvic (p<0.01) or paraaortic (p<0.01) lymph node
      metastases. Further, PD-ECGF was significantly lower in mucinous than in serous
      adenocarcinomas (p<0.05). No significant correlation was seen between PD-ECGF and
      histologic grade, maximum intraperitoneal metastatic tumor diameter (<2 vs.>2
      cm), or presence of demonstrable malignant cells in peritoneal fluid. In stage
      III disease, PD-ECGF exhibited significant correlation with recurrence (p<0.05).
      Our data suggested that results of PD-ECGF assays in primary tumors can predict
      progression and recurrence of EOC.

PMID- 14568173
TI  - Establishment and characterization of pheochromocytoma tumor models expressing
      different levels of trkA receptors.
AB  - To date experimental in vivo pheochromocytoma (PC) models have not been
      available. A major in vitro PC model consists of PC12 cells that respond to nerve
      growth factor (NGF) by differentiation, mediated by the trkA receptor. We report
      the establishment of PC12 tumor models expressing low and high levels of trkA
      receptor in CD1 nude mice. The tumors are characterized by their responsiveness
      to NGF, karyotype, presence of enolase, and chromaffin granules, as well as
      dopamine release. These novel PC models facilitate research on the role of the
      trkA receptor in cancer and the development of trkA-selective anti-cancer agents.

PMID- 14568174
TI  - Regulation of metallothionein and zinc transporter expression in human prostate
      cancer cells and tissues.
AB  - Prostate glands contain heavy metals such as zinc and cadmium, and
      epidemiological studies showed that both metals were associated with prostate
      cancer development. To understand the heavy metal metabolism in prostate glands,
      we investigated the regulation of metallothionein (MT), metal-responsive promoter
      element-binding transcription factor (MTF) and zinc transporter (ZnT) in human
      prostate cells and tissues. Growth of human prostate cancer cells, LNCaP and PC-3
      cells, was suppressed by zinc or cadmium treatment in a dose-dependent manner.
      LNCaP cells expressed MT-1A, 1X and 2A mRNA, and PC-3 cells expressed MT-1X and
      2A mRNA. Zinc or cadmium treatment up-regulated MTs, MTF-1 and ZnT-1 gene
      expression levels in both cell lines. In PC-3 cells, ZnT-1 protein was detected,
      and was up-regulated by the metal treatment. Human prostate cancer tissues
      expressed significantly lower levels of ZnT-1 gene in comparison with
      hyperplastic tissues. We demonstrated the ZnT-1 expression in human prostate for
      the first time. The present study showed that heavy metal-metabolizing proteins
      were involved in human prostate homeostasis, and that the metal metabolizing
      system might be different in malignant tissues.

PMID- 14568175
TI  - Diagnostic significance of antibodies to heat shock proteins.

PMID- 14568176
TI  - Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry in
      clinical chemistry.
AB  - Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      (MALDI-Tof-MS) has recently become a popular and versatile method to analyze
      macromolecules from biological origin. In this paper, we will review the
      application of MALDI-Tof-MS in clinical chemistry and biology. MALDI-Tof-MS is
      used in clinical chemistry, e.g. disease markers can be identified with MALDI-MS
      analysis in combination with 1-D and 2-D gel electrophoresis separations thanks
      to either peptide mass fingerprinting (PMF) or peptide sequence tag (PST)
      followed by data base searching. In microbiology, MALDI-Tof-MS is employed to
      analyze specific peptides or proteins directly desorbed from intact viruses,
      bacteria and spores. The capability to register biomarker ions in a broad m/z
      range, which are unique and representative for individual microorganisms, forms
      the basis of taxonomic identification of bacteria by MALDI-Tof-MS. Moreover, this
      technique can be applied to study either the resistance of bacteria to
      antibiotics or the antimicrobial compounds secreted by other bacterial species.
      More recently, the method was also successfully applied to DNA sequencing
      (genotyping) as well as screening for mutations. High-throughput genotyping of
      single-nucleotide polymorphisms has the potential to become a routine method for
      both laboratory and clinical applications. Moreover, posttranscriptional
      modifications of RNA can be analyzed by MALDI using nucleotide-specific RNAses
      combined with further fragmentation by post source decay (PSD).

PMID- 14568177
TI  - Amelioration of radiation-induced oxidative stress and biochemical alteration by
      SOD model compounds in pre-treated gamma-irradiated rats.
AB  - INTRODUCTION: The role of metalloelements in tissue maintenance, function and
      response to injury offer a new approach to decreasing and/or treating radiation
      injury. We investigated the roles of CuL(2)SO(4), [MnL(2)O](2)Cl(4)(H(2)O)(2) and
      [(VL(2)O)(VL(2)H(2)O)]Cl(6) complexes (L=2-methylaminopyridine) of SOD-mimetic
      activities, in ameliorating the radiation-induced oxidative stress and
      alterations in some biochemical parameters in liver, kidney, spleen and brain in
      pretreated female rats exposed to gamma-irradiation. METHODS: Both untreated-rats
      and rats treated with the above complexes were subjected to whole-body gamma
      irradiation (6 Gy). 5'-Nucleotidase (5'-NT), acetylcholinesterase (AChE),
      adenosne triphosphatase (ATPase), superoxide dismutase (SOD), catalase (CAT) and
      glutathione reductase (GSSG-R) were assessed as well as liver DNA and RNA
      contents and total protein concentration were estimated in tissue homogenates of
      the above organs. The same parameters were assessed in non-irradiated treated
      rats and normal control rats. Results were compared to irradiated non-treated and
      normal control rats. RESULTS: Pretreatment of gamma-irradiated rats with Mn(IV)
      or V(IV) complex produced a significant decrease in liver 5'-NT activity compared
      to the corresponding value of the untreated irradiated rats. In contrast, liver
      DNA and RNA contents and brain AChE and ATPase activities were significantly
      increased in irradiated rat group pre-treated with these metal complexes. Cu II,
      Mn IV or V IV complex inoculation prior to irradiation of normal rats exhibited a
      significant increase in SOD, CAT, GSSG-R activities and protein content of liver,
      kidney, spleen and brain homogenates compared with that of the untreated
      irradiated rats. The treatment of non-irradiated rats with these complexes
      produced a highly significant increase in mean activities of SOD and CAT, with no
      changes in other parameters vs. controls. CONCLUSIONS: Cu(II), Mn(IV) and V(IV) 2
      methylaminopyridine complexes offer a physiological approach to ameliorate the
      radiation-induced biochemical alterations. In addition, they provide sufficient
      protection against radiation injury of radiosensitive tissues.

PMID- 14568179
TI  - Lymphocyte DNA alteration by sub-chronic ethanol intake in alcohol-preferring
      rats.
AB  - BACKGROUND: Excessive alcohol consumption has been correlated with a higher
      susceptibility to infections among humans. Chromosome aberrations and other
      parameters have been suggested as useful biomarkers in assessing genetic damage
      due to ethanol intake. METHODS: Genetically selected alcohol-preferring rats were
      given water, 10% ethanol and water or 10% ethanol alone for 3 months as fluid to
      drink. Food was available ad libitum for the entire period. At the end of the sub
      chronic treatment their blood and liver were collected. All blood cells were
      counted and both lymphocytes and hepatocytes of all three groups were tested with
      the Comet assay to determine whether any DNA damage had occurred. RESULTS: Only
      lymphocytes showed DNA damage, with differences among groups. The group that had
      only ethanol to drink showed greater lymphocyte DNA damage than the ethanol/water
      and water alone groups. On the other hand, hepatocyte DNA did not show any signs
      of damage. CONCLUSIONS: Ten weeks of sub-chronic ethanol treatment produces small
      but significant damage to lymphocytes but not to hepatocytes, a result which
      confirms the observations of previous authors, and extends them even to a strain
      of rats genetically selected for high ethanol intake.

PMID- 14568178
TI  - Different acute responses of serum type I collagen telopeptides, CTX, NTX and
      ICTP, after repeated ingestion of calcium.
AB  - BACKGROUND: N- and C-terminal fragments of type I collagen such as NTX, CTX and
      ICTP are released into circulation during bone resorption and can be quantified
      in serum. Their respective sensitivity as indices of osteoclastic activity was
      compared after a short-term inhibition of resorption induced by repeated drinking
      of calcium-fortified water. METHODS: Serum NTX, CTX and ICTP were measured by
      specific immunoassays in one group of 15 subjects sampled at 08.00, 11.00, 14.00
      and 17.00 (referred to as T0, T3h, T6h and T9h) and having ingested in two
      experimental periods 660 ml of either low-calcium mineral water or the same low
      calcium mineral water fortified with calcium (300 mg/l) at three times (08.00,
      11.00 and 14.00). RESULTS: Oral intake of calcium-fortified water resulted in
      progressive decrease in serum CTX (by 38.7% at T3h, 61.0% at T6h and 60.4% at
      T9h) and NTX (by 19.0% at T3h, 24.1% at T6h and 25.2% at T9h) while serum ICTP
      concentrations were not significantly affected. Since ingestion of low-calcium
      water induced a modest but significant decrease in both CTX (-19.4%) and NTX (
      10.6%) we compared the two sets of assays with repeated-measures two-factor
      analysis of variance with interaction. Ingestion of calcium-fortified water vs.
      low-calcium water resulted in a significant decrease in both serum CTX (time,
      P<0.0001; treatment, P<0.0001; time-by treatment, P<0.0001) and NTX (time,
      P<0.0001; treatment, P=0.0001; time-by treatment, P=0.0066). CONCLUSIONS: CTX is
      more sensitive than NTX while ICTP is not sensitive to calcium-induced acute
      changes in osteoclastic activity. The present results stress the importance of
      choosing appropriate biochemical bone markers to demonstrate the effects of
      calcium on bone resorption.

PMID- 14568180
TI  - Normal ranges of non-fasting triglycerides in healthy Dutch males and females.
AB  - BACKGROUND: Increased triglycerides (TG) are associated with atherosclerosis. We
      determined free-living non-fasting TG concentrations in healthy Dutch subjects.
      METHODS: Capillary TG (TGc) was self-measured by 109 males and 104 females during
      3 days, on six fixed time-points each day; fasting, before and 3 h after lunch,
      before and 3 h after dinner and at bedtime. Daylong TGc-profiles were calculated
      as area under the mean TGc-curve (TGc-AUC). Reference values for "high" and
      "normal" daylong TGc concentrations were calculated as the 95th and 75th
      percentiles, respectively. RESULTS: Fasting TGc were higher in males compared
      with females (1.41+/-0.75 versus 1.27+/-0.59 mmol/l), resulting in higher TGc-AUC
      (25.4+/-10.4 versus 20.6+/-9.8 mmol h/l). The highest TGc-concentrations were
      found in the evening. The majority of subjects (95%) had TGc during the evening
      below 4.6 mmol/l in males and below 3.7 mmol/l in females. Seventy-five percent
      of the subjects had TGc during the evening below 2.9 mmol/l in males and below
      2.2 mmol/l in females. During the day (with exclusion of post-dinner TGc), 95% of
      the subjects had TGc below 3.7 mmol/l in males and below 3.6 mmol/l in females.
      Finally, 75% of the subjects had TGc during the day below 2.5 mmol/l in males and
      1.7 mmol/l in females. CONCLUSIONS: The present data may help to delineate normal
      ranges of non-fasting TG and could be used to detect groups at risk for
      atherosclerosis on the basis of a disturbed TG metabolism.

PMID- 14568181
TI  - Serum levels of Hemorphin-7 peptides in patients with breast cancer.
AB  - BACKGROUND: Increased expression of cathepsin D (CD) and B (CB) is found in some
      cancers and correlates with the development of clinical metastases. It was
      suggested that these cathepsins could be used as prognostic markers, especially
      CD in breast cancer. Because serum level of Hemorphin-7 (H7) peptides could
      reflect CD activity, we have hypothesised that it could be used as a prognostic
      factor in breast cancer. METHODS: To verify this hypothesis, H7 serum levels from
      62 breast cancer patients and 25 healthy controls were measured by ELISA.
      RESULTS: The mean serum concentration of H7 was 2.27+/-0.63 mumol/l in breast
      cancer patients in comparison with 4.09+/-1.05 mumol/l in controls (p=0.002).
      This reduced level of H7 in breast cancer could be due to the over-expression of
      CB, which exhibits strong interaction with H7 in vitro, with a ratio K(cat)/K(m)
      estimated at 18000 s(-1) M(-1). CONCLUSIONS: Because H7 serum levels did not
      correlate with other parameters including age, CA15-3 and ACE markers, it seems
      that they might be used as independent markers for the diagnosis of breast
      cancer.

PMID- 14568182
TI  - Sequential injection analysis of nitrites and nitrates in human serum using
      nitrate reductase.
AB  - BACKGROUND: Nitrates and nitrites, as products of nitric oxide in human serum,
      are currently used as markers in many diseases. A sequential injection analysis
      (SIA) flow system, for their determination in serum, is presented. The exact
      timing of fluidic manipulations and the small volumes used in the automated SIA
      systems provide exquisite control of the reaction conditions and an economy in
      the biological fluid and enzymes used. METHODS: For nitrite determinations, 150
      microl of sample and 50 microl of Griess reagent were sequentially aspirated to
      the system and sent to the detector. Nitrates were determined as nitrites after
      reduction through 0.09 U of nitrate reductase and 75 microl of NADPH. RESULTS:
      Nitrates and nitrites were determined at concentrations up to 4 and 3 mg/l,
      respectively, with relative standard deviation (rsd) <5%. Detection limits of
      0.14 and 0.03 mg/l, respectively, were calculated. Statistical evaluation showed
      good agreement between the results obtained, for 15 deproteinized serum samples,
      with both the SIA system and the comparison batch procedure. CONCLUSIONS: The
      automatic developed method seems to be a good alternative for routine
      implementation since it is four times faster, and it requires one third of sample
      and one half of nitrate reductase than the comparison batch procedure.

PMID- 14568183
TI  - Immune-enhancement effect of the herbal combination Allergina.
AB  - BACKGROUND: The herbal formulation, Allergina, has long been used for various
      diseases. It is known to have an anti-microbial and anti-virus activity. However,
      it is still unclear how Allergina has these effects in experimental models. We
      investigated the effect of Allergina on the proliferation of T cell and
      production of cytokines in human T-cell line, MOLT-4 cells, and mouse peritoneal
      macrophages. METHODS: The MOLT-4 cells were cultured for 24 h in the presence or
      absence of Allergina. Allergina significantly increased the cell viability by
      26.9+/-5.4% (P<0.05) and interleukin (IL)-2, IL-4 and interferon (IFN)-gamma
      production compared with media control (about 4-fold for IL-2, 2.5-fold for IL-4
      and 3.4-fold for IFN-gamma, P<0.05). Maximal effective concentration of Allergina
      was 1 mg/ml for IL-2 and, 0.01 mg/ml for IL-4 and IFN-gamma. Allergina alone or
      Allergina plus recombinant IFN-gamma (rIFN-gamma) increased the production of
      tumor necrosis factor (TNF)-alpha, but Allergina decreased the production of TNF
      alpha on rIFN-gamma plus LPS-stimulated macrophages. In addition, Allergina
      increased the production of IL-12 on mouse peritoneal macrophages and peripheral
      blood mononuclear cells. CONCLUSION: Allergina may have an immune-enhancement
      effect through the cytokine production.

PMID- 14568184
TI  - The potential beneficial effect of leptin on an experimental model of
      hyperlipidemia, induced by chronic ethanol treatment.
AB  - BACKGROUND: Obesity is known to predispose individuals to liver disease by
      increasing hepatic sensitivity to endotoxin. The aim of the present study was to
      determine the effect of mouse recombinant leptin on food intake, body weight,
      hepatic and plasma lipids and lipoproteins in alcohol-induced liver injury.
      METHOD: Male Swiss mice weighing 28-32 g were administered ethanol (6.32 g x kg(
      1) body weight, p.o.) for the first 30 days. Subsequently, ethanol-fed mice were
      given intraperitoneal injections of exogenous leptin (230 microg x kg(-1) body
      weight, i.p.) every alternate day for 15 days. At the end of the total
      experimental period of 45 days, plasma concentrations of total cholesterol, free
      fatty acids, triglycerides, lipoprotein lipase and lipoproteins were measured.
      RESULTS: Exogenous leptin injections to alcohol-fed mice significantly (P<0.05)
      inhibited the rise in hepatic and plasma lipid and lipoprotein concentrations as
      compared with those of the unsupplemented ethanol fed mice. Food intake and
      average body weight at the end of the experimental period was significantly
      decreased on leptin administration. CONCLUSION: Chronic administration of
      exogenous mouse recombinant leptin prevents the rise in lipids and lipoprotein
      concentrations significantly in an animal model of alcohol-induced
      hyperlipidemia.

PMID- 14568185
TI  - Modulation of Chelidonii herba on glycine-activated and glutamate-activated ion
      currents in rat periaqueductal gray neurons.
AB  - BACKGROUND: Chelidonii herba is classified as Papaver somniferum L. Aqueous
      extract from C. herba is traditionally used for disorders with symptoms like
      pain, bloating, abdominal cramp after meals. METHODS: Modulation of C. herba on
      glycine-activated and glutamate-activated ion currents in the acutely dissociated
      periaqueductal gray (PAG) neurons was investigated by the nystatin-perforated
      patch-clamp technique. RESULTS: C. herba inhibited glycine-activated ion current
      and increased glutamate-activated ion current. C. herba-induced inhibition on
      glycine-activated ion current is implicated in opioid receptors and GTP-binding
      proteins (G-proteins). Increased glutamate-activated ion current induced by C.
      herba is linked neither by opioid receptors nor GTP-binding proteins.
      CONCLUSIONS: Suppressed glycine-induced response and elevated glutamate-induced
      response by C. herba may increase neuronal excitability in PAG, results in
      activation of descending pain control system, and this mechanism can be suggested
      as one of the analgesic actions of C. herba.

PMID- 14568186
TI  - A comparison of in vitro acylcarnitine profiling methods for the diagnosis of
      classical and variant short chain acyl-CoA dehydrogenase deficiency.
AB  - BACKGROUND: Homozygosity and compound heterozygosity for the short chain acyl-CoA
      dehydrogenase (SCAD) gene sequence variants 625G-->A and 511C-->T are associated
      with ethylmalonic aciduria (EMA), a biochemical indicator of SCAD deficiency. The
      clinical and biochemical implications of these variants are not fully understood.
      The effect of these variants on the accumulation of butyrylcarnitine by
      fibroblasts in culture was studied. METHODS: In vitro acylcarnitine profiling in
      fibroblasts was carried out using [U-13C]-labeled or unlabeled palmitate in the
      presence of excess L-carnitine, with or without a medium chain acyl-CoA
      dehydrogenase (MCAD) inhibitor. Acylcarnitines were analyzed using tandem mass
      spectrometry. 625G/625G (wild type), 625G/625A and 625A/625A (variant) control
      fibroblasts were compared with fibroblasts from patients homozygous for
      inactivating SCAD mutations (SCAD deficient) and from patients with EMA who were
      homozygous or compound heterozygous for the SCAD variants. RESULTS: Variant
      control and patient fibroblasts accumulated moderate amounts of butyrylcarnitine
      compared with wild-type controls and in contrast to the significant amount of
      butyrylcarnitine accumulated by SCAD deficient fibroblasts, regardless of
      incubation conditions. CONCLUSIONS: Moderately reduced SCAD activity associated
      with SCAD variants can be detected using in vitro acylcarnitine profiling
      methods, which may be used as an indirect measure of SCAD activity.

PMID- 14568187
TI  - Steroid hormone regulation of the human kallikrein 10 (KLK10) gene in cancer cell
      lines and functional characterization of the KLK10 gene promoter.
AB  - BACKGROUND: The human kallikrein 10 (KLK10) gene is a new member of the human
      tissue kallikrein gene family. It encodes for a secreted serine protease (hK10)
      with predicted trypsin-like enzymatic activity. KLK10 is highly expressed in the
      sex organs and its expression level changes in malignancy. METHODS: To determine
      the role of steroid hormones in KLK10 gene expression, we investigated its
      modulation by 17beta-estradiol, 5alpha-dihydrotestosterone, norgestrel,
      dexamethasone and aldosterone, at both the transcription and translation level,
      in a panel of cancer cell lines. After steroid hormone stimulation, the change of
      KLK10 mRNA was monitored with reverse transcriptase polymerase chain reaction and
      hK10 protein levels in the culture supernatant were quantified with an hK10
      specific immunoassay. The presence of hormone response elements in the KLK10 gene
      promoter was examined with the chloramphenicol acetyltransferase reporter gene
      system. RESULTS: The KLK10 expression was mainly up-regulated by estrogens,
      androgens and progestins, and to a lesser extent by dexamethasone and aldosterone
      in the breast cancer cell lines BT-474, MCF-7 and T-47D, both at the mRNA and
      protein levels. The effect of stimulation of these steroids on KLK10 expression
      varied among the cell lines. Estrogens, androgens and progestins were most potent
      in the BT-474, T-47D and MCF-7 cells, respectively. The up-regulation effect of
      estrogens, androgens, and progestins on KLK10 expression can be blocked by their
      antagonists ICI-182, 780, RU-56,187, and mifepristone, respectively. Time course
      studies showed that hK10 protein started to increase 1 day after steroid hormone
      stimulation and this increase persisted for 7 days. These data suggest that
      steroid hormones up-regulate KLK10 gene expression through direct interaction
      between hormone-receptor complexes and their cognate hormone response elements.
      To search for hormone response elements, we functionally characterized the KLK10
      promoter by placing it upstream of the chloramphenicol acetyltransferase reporter
      gene. We found that KLK10 promoter activity did not rely on the presence of
      functional estrogen and androgen receptors. Also, the presence of functional
      estrogen and androgen receptors did not increase its constitutive activity. We
      suggest that the hormone response elements that mediate the transcriptional
      regulation of KLK10 are unlikely to locate in the KLK10 promoter. CONCLUSIONS:
      Estrogens, androgens and progestins modulate KLK10 expression through their own
      receptors but this regulation is not mediated by steroid hormone response
      elements in the promoter of the KLK10 gene.

PMID- 14568188
TI  - Increased protein glycation in non-diabetic pediatric nephrotic syndrome:
      possible role of lipid peroxidation.
AB  - BACKGROUND: Malondialdehyde (MDA), ascorbic acid and reduced glutathione (GSH)
      have been reported to play a possible role in glycation of proteins. This study
      was performed to evaluate this correlation in nephrotic syndrome patients by
      comparing the levels of fructosamine with MDA, ascorbic acid and GSH. METHODS:
      Fifteen children with nephrotic syndrome during relapse and 10 age- and sex
      matched healthy controls were enrolled for this study. Whole blood GSH, plasma
      MDA, total ascorbic acid and fasting glucose were analyzed in both the groups.
      Partial correlation analysis was performed to predict the independent association
      of MDA, ascorbic acid and GSH on fructosamine. RESULTS: Plasma MDA and
      fructosamine levels were found to be increased in nephrotic syndrome patients
      when compared with controls. Plasma ascorbic acid and whole blood GSH were
      decreased in nephrotic group vs. healthy controls. Partial correlation analysis
      showed a significant positive correlation between fructosamine and MDA.
      CONCLUSIONS: Present data point to a possible involvement of MDA in the glycation
      of protein in non-diabetic nephrotic syndrome patients, and provide support for
      the potential use of an antioxidant therapy in these patients.

PMID- 14568189
TI  - Effect of CD40--CD40 ligand interaction on diacylglycerol-protein kinase C and
      inositol trisphosphate-Ca(2+) signal transduction pathway in human umbilical vein
      endothelial cells.
AB  - BACKGROUND: Increasing evidence shows that CD40-CD40L interaction plays a crucial
      role in the pathogenesis of atherosclerosis and coronary artery disease. The
      mechanism of CD40-CD40L interaction might be related to signal transduction via
      receptor. The transduction pathway of the CD40 receptor may involve the
      activation of phospholipase C (PLC) which induces the production of inositol
      trisphosphate (IP(3)) leading to the increase of the intracellular free calcium
      on one hand, and of diacylglycerol (DAG) which stimulates the translocation to
      the membrane of protein kinase C (PKC). METHODS: Endothelial cells were isolated
      from human umbilical vein and incubated with indicated concentrations of CD40
      ligand (CD40L) for various periods. The DAG levels in HUVEC were studied with
      radioenzymatic assay. Quantitative measurements of 32P phosphatidic acid were
      performed by thin-layer chromatography and autoradiography. IP(3) was
      quantitatively measured by the radioreceptor binding assay. The activity of PKC
      and [Ca(2+)]i induced by CD40L were measured by its ability to transfer phosphate
      from [gamma-32P]ATP to lysine-rich histone and flow cytometric analysis loading
      with the Ca(2+) dye fluo3/Am, respectively. RESULTS: The DAG levels were raised
      by CD40L in a dose-dependent, biphasic manner. The early phase was rapid and
      transient, peaking at 20 s; and the late phase reached the maximal level at 10
      min and then decayed slowly. CD40L increased the PKC total activity in a dose
      dependent manner with phase peaking at 12 min, then decreased slowly and
      maintained for at least 20 min. The results also showed that CD40L induced PKC
      activity translocation from the cytosolic to membrane. Similarly, the CD40L
      induced transient IP(3) formation was coincident with the first peak of DAG
      formation. Moreover, CD40L also induced biphasic [Ca(2+)]i responses including
      the rapid initial transient phase and the sustained phase. Anti-CD40 monoclonal
      antibody can significantly suppress CD40L-induced DAG-PKC and IP(3)-[Ca(2+)]i
      signal pathway activation in HUVEC. CONCLUSIONS: CD40-CD40 ligand interaction can
      induce a robust stimulation of the DAG-PKC and inositol trisphosphate-Ca(2+)
      signal transduction pathway in HUVEC.

PMID- 14568190
TI  - Tamoxifen might influence the affinity of LPL for heparin-sepharose.
AB  - BACKGROUND: We previously reported that the tamoxifen treatment caused a decrease
      in lipoprotein lipase (LPL) activity and an increase in LPL mass. We hypothesized
      that tamoxifen may increase the quantity of inactive LPL. METHODS: Lipoprotein
      lipase in post-heparin plasma usually exists in both monomeric and dimeric forms,
      which may be separated on a heparin-Sepharose column with different salt
      concentrations. Lipoprotein lipase in post-heparin plasma from postmenopausal
      patients with hypertriglyceridemia treated with or without tamoxifen was
      incubated with or without 4-hydroxy-tamoxifen (4-OHT), the monomers and dimers
      were separated on a heparin-Sepharose column and their masses were measured.
      RESULTS: The masses of total LPL and dimeric LPL of tamoxifen-treated patients
      were significantly higher than those of control subjects. Monomeric LPL of
      tamoxifen-treated patients passed more slowly through the heparin-Sepharose
      column compared with that of control subjects. The ratio of monomeric LPL to
      dimeric LPL of tamoxifen-treated patients was 0.61, significantly lower than that
      of control subjects, which was 1.45 (p<0.01). In addition, monomeric LPL
      incubated with 4-OHT passed more slowly through the heparin-Sepharose column
      compared with that incubated without 4-OHT. CONCLUSION: Tamoxifen influences the
      affinity of LPL for heparin.

PMID- 14568191
TI  - Measurement of plasma hydroperoxide concentration by FOX-1 assay in conjunction
      with triphenylphosphine.
AB  - INTRODUCTION: Hydroperoxides are well-recognized reactive oxygen species which
      are associated with oxidative stress, a phenomenon of current clinical interest
      as oxidative stress is associated with a number of disease condition. Ferrous ion
      oxidation xylenol orange (FOX) methods of hydroperoxide estimation has outdated
      other methods available for hydroperoxide estimation. Two versions FOX assays are
      described in the literature, FOX-1 and FOX-2, in which FOX-1 is more sensitive.
      METHODS: we increased the sensitivity of FOX-1 assay by stabilizing the reagent
      pH 1.7-1.8. Analogous to FOX-2 assay, we have modified FOX-1 assay by using it in
      conjunction with triphenylphosphine and butylated hydroxytoluene, thus increasing
      the specificity of FOX-1 assay for hydroperoxide. By modified FOX-1 method, we
      estimated plasma hydroperoxide concentration of normal human subjects and of
      diabetic patients and compared with FOX-2 method. RESULTS: The FOX-1 method
      showed a significant high value of plasma hydroperoxide concentration compared to
      FOX-2 method both in normal subjects and diabetic patients with a significant
      correlation. By modified FOX-1 method, the recovery percentage of cumene
      hydroperoxide was better in biological samples when compared to FOX-2 method.
      CONCLUSION: The modified FOX-1 method is equally specific for hydroperoxide
      determination when compared to FOX-2 but is more sensitive.

PMID- 14568192
TI  - The level of pre-heparin serum lipoprotein lipase mass at different stages of
      pregnancy.
AB  - BACKGROUND: Lipoprotein lipase (LPL) mass is present in pre-heparin serum,
      although its activity is rarely detected. To clarify the dynamics of pre-heparin
      LPL mass during pregnancy, we studied the relationship between pre-heparin LPL
      mass and lipids in normal pregnant women. METHODS: Pre-heparin LPL mass and serum
      lipid levels were measured in 99 pregnant women during all three trimesters.
      RESULTS: When compared with the first and second trimesters, a significant
      decrease in pre-heparin LPL mass was observed in the third trimester. Plasma
      triglycerides were negatively correlated with pre-heparin LPL mass (r=-0.30;
      p<0.05). In contrast, LDL-C, HDL-C and total cholesterol did not exhibit a
      statistically significant correlation. CONCLUSION: The decrease in pre-heparin
      LPL mass is manifested only during the third trimester.

PMID- 14568193
TI  - Age-related increase of plasma platelet-activating factor concentrations in
      Chinese.
AB  - BACKGROUND: Platelet-activating factor (PAF) is a potent bioactive phospholipid,
      which may be one of the determinants of atherogenesis. The purpose of this study
      was to investigate the relationship between the concentrations of plasma platelet
      activating factor and age in a common Chinese population. METHODS: Two-hundred
      seventy-nine Han nation subjects (male: n=162; female: n=117) who had visited two
      hospitals for overall health survey, as an annual medical check-up or for other
      reasons by clinical examinations were recruited and divided into six age groups
      (21-30, 31-40, 41-50, 51-60, 61-70, 71-80 years). PAF was extracted from their
      plasma and purified by thin-layer chromatography (TLC). The PAF concentrations
      were detected by radioimmunoassay. RESULTS: The PAF concentrations (pg/ml) in
      plasma showed significantly age-related increase (r=0.3348, P<0.01, n=279). In
      the 21-30-year group, the PAF concentration was 338+/-96 pg/ml. Except for the 31
      40-year group, the PAF concentrations in other four groups were all higher than
      that of the 21-30-year group (P<0.05, P<0.01, P<0.001 and P<0.001, respectively).
      CONCLUSIONS: Considering PAF is one of the key factors relevant to progression of
      atherogenesis, and the high concentrations of plasma PAF may therefore serve as a
      marker for the risk of atherosclerosis. Adjustment of the concentrations of
      plasma PAF correlated with aging may be helpful to reducing the prevalence rate
      of multi-senile arteriosclerosis occlusive diseases.

PMID- 14568194
TI  - Oxidative changes and desialylation of serum proteins in hyperthyroidism.
AB  - BACKGROUND: Hyperthyroidism is associated with oxidative stress. Thyroid hormones
      are observed to influence the metabolism of plasma proteins. The present study
      was carried out to explore the level of sialic acid content and the oxidative
      changes of serum proteins in hyperthyroid subjects and matched healthy controls.
      METHODS: Blood was collected from 10 hyperthyroid patients and 10 age and sex
      matched healthy control subjects. The extent of carbonylation and desialylation
      of serum protein was estimated by dinitrophenylhydrazine and thiobarbituric acid
      methods, respectively. The protein cleavage and cross-linking were studied by
      separating serum protein in SDS-PAGE. The effects of in-vitro treatment of serum
      proteins with H(2)O(2) on the above-mentioned parameters were observed. RESULTS:
      The carbonylation was significantly higher and the sialic acid content was
      significantly lower in serum proteins of hyperthyroid cases in comparison to that
      of controls. Serum proteins were found to have increased levels of cleavage and
      cross-linking in hyperthyroid cases. The high molecular weight proteins were
      mostly cleaved. In-vitro treatment of serum proteins with H(2)O(2) led to similar
      changes. CONCLUSIONS: The study indicated that in hyperthyroidism, serum proteins
      undergo increased levels of oxidative changes leading to high turnover rate of
      blood proteins. A significant negative correlation between carbonylation and
      sialic acid content of serum proteins in hyperthyroidism and enhanced
      desialylation and carbonylation of serum proteins by in-vitro H(2)O(2) treatment
      suggest that oxidative stress can cause desialylation of serum glycoproteins.

PMID- 14568195
TI  - Age and gender as risk factors for hyponatremia and hypernatremia.
AB  - BACKGROUND: This study assesses gender and age as independent risk factors for
      hypo- and hypernatremia and describes the prevalence of hypo- and hypernatremia
      in different population groups. METHODS: Details of all serum Na results with
      accompanying patient demographics for 2 years were downloaded from the laboratory
      database into Microsoft Access for multiple logistic regression analysis using
      SPSS. Female gender and age <30 years were the reference groups. RESULTS: Data
      from 303577 samples on 120137 patients were available for analysis. Prevalence at
      initial presentation to a health care provider of Na<136, <116, >145, and >165
      mmol/l were for acute hospital care patients: 28.2%, 0.49%, 1.43%, and 0.06%;
      ambulatory hospital care: 21%, 0.17%, 0.53%, and 0.01%; community care: 7.2%,
      0.03%, 0.72%, and <0.01%. Age odds ratios rose with increasing age to 1.89 and
      8.70 (Na<136 and <116 mmol/l) and 7.09 and 24.39 (Na>145 and >165 mmol/l,
      respectively) for age >81 years. Male gender was a mild risk factor for Na<136
      mmol/l and was otherwise unimportant. CONCLUSIONS: Hyponatremia is a common but
      generally mild condition while hypernatremia is uncommon. Increasing age is a
      strong independent risk factor for both hypo- and hypernatremia. Gender is not an
      important risk factor for disturbances of serum Na concentration.

PMID- 14568196
TI  - Unusually high concentrations of cTnI and cTnT in a patient with catastrophic
      antiphospholipid antibody syndrome.
AB  - BACKGROUND: We present a case of a patient with catastrophic antiphospholipid
      antibody syndrome with unusually high concentrations of cardiac Troponin I (cTnI)
      and cardiac Troponin T (cTnT). Troponins are sensitive and specific markers of
      myocardial injury. The degree of their elevation, in the context of the chronic
      autoimmune condition of the patient, elicited a thorough investigation for the
      presence of interfering antibodies. METHODS: Cardiac markers, including total CK,
      CK-MB, cTnI, and cTnT, were measured in this patient over a period of 14 days
      after the onset of symptoms. In order to rule out a possible interference, serum
      samples were subjected to serial dilutions and were incubated with a blocking
      reagent (HBR) prior to analysis. RESULTS: The time release of the cardiac markers
      into the systemic circulation of this patient followed the typical pattern after
      a myocardial infraction. Serial dilutions of the samples, and incubation with the
      blocking reagent revealed no indication of the presence of interfering
      antibodies. CONCLUSIONS: The results strongly suggest that the extremely high
      concentrations of cTnT and cTnI in this patient were real and indicative of a
      massive myocardial infarction (MI). These may be the highest concentrations of
      cTnI and cTnT reported in the systemic circulation of a single patient.

PMID- 14568198
TI  - Interindividual variability of whole blood viscosity improved with standardized
      hydration.

PMID- 14568197
TI  - Effect of tamoxifen on fibrinogen, D-dimer, lipid and lipoprotein concentrations
      in breast cancer patients.

PMID- 14568199
TI  - Glucose autoxidation produces acrolein from lipid peroxidation in vitro.

PMID- 14568201
TI  - Towards a mathematical model of the aortic reservoir.
AB  - It is well known from experiments that the circulation is going on under
      physiological parameters, only if the rigidity of the aortic wall is sufficiently
      small. We show that the result can be confirmed by the one-dimensional
      mathematical model describing the dynamics of the aortic reservoir (AR) by means
      of a hyperbolic system of PDE.

PMID- 14568202
TI  - Classification of dynamics of a model of motor coordination and comparison with
      Parkinson's disease data.
AB  - In our recent reports motor coordination of human lower limbs has been
      investigated during pedaling a special kind of ergometer which allows its left
      and right pedals to rotate independently. In particular, relative phase between
      left and right rotational-velocity waveforms of the pedals and their amplitude
      modulation have been analyzed for patients with Parkinson's disease (PD). Several
      patients showed peculiar interlimb coordination different from the regular anti
      phase pattern of normal subjects. We have reported that these disordered patterns
      could be classified into four groups. Moreover, it has been demonstrated that a
      mathematical model could reproduce most of the disordered patterns. Such a model
      includes a schematization of the central pattern generator with two identical
      half-centers mutually coupled and two tonic control signals from higher motor
      centers, each of which inputs to one of the half-centers. Depending on the
      intensities of the tonic signals and on the differences between them, the model
      could generate a range of dynamics comparable to the clinically observed
      disordered patterns. In this paper, we explore the dynamics of the model by
      varying the intensities of the tonic signals in the model. Using the same method
      used for classifying the clinical data, the dynamics of the model are classified
      into several groups. The classified groups for the simulated data are compared
      with those for the clinical data to look at qualitative correspondence. Our
      systematic exploration of the model's dynamics in a wide range of the parameter
      space has revealed global organization of the bifurcations including Hopf
      bifurcations and cascades of period-doubling bifurcations among others,
      suggesting that the bifurcations, induced by instability of stable dynamics of
      the human motor control system, are responsible for the emergence of the
      disordered coordination in PD patients.

PMID- 14568203
TI  - Stochastic resonance in a sinusoidally forced LIF model with noisy threshold.
AB  - In this report, the LIF neural model driven by underthreshold sinusoidal signals
      but with a gaussian-distributed noise on the threshold, is approximated by
      suitably defining an instantaneous firing (or escape) rate, which depends only on
      the momentary value of the voltage variable. This allows us to obtain, by
      analytically solving the relevant equations, the main statistical functions
      describing the "firing activity"; namely, the probability density function of
      firing phases and that of interspike intervals. From these functions two
      quantities can be derived, whose dependence on the noise intensity allows the
      Stochastic Resonance (SR) to be demonstrated. Besides the "regular" SR, the
      analysed system was found to produce, either for low frequencies and large
      amplitudes of modulation or for high modulation frequencies, resonance curves
      displaying two peaks. This bimodal feature of the resonance curves is accounted
      for on the basis of phase locked firing patterns.

PMID- 14568204
TI  - Oscillatory neural network model of attention focus formation and control.
AB  - A new mechanism to control attention focus formation and switching in the model
      of selective attention is suggested and studied. The model is based on an
      oscillatory neural network (ONN) with the star-like architecture and phase shifts
      in connections between oscillators. Attention is modelled as a dynamical mode of
      partial synchronisation between a particular subgroup of oscillators and the
      central oscillator (CO). A new theoretical method to study full and partial
      synchronisation in the system is presented. Equations for the frequency of
      synchronisation are derived which allow the programming of the dynamical
      behaviour of the system depending on the parameters. In particular, we show that
      phase shifts in connections between oscillators provide an efficient mechanism of
      attention control.

PMID- 14568205
TI  - Oscillations, resonances and noise: basis of flexible neuronal pattern
      generation.
AB  - Modulation of neuronal impulse pattern is examined by means of a simplified
      Hodgkin-Huxley type computer model which refers to experimental recordings of
      cold receptor discharges. This model essentially consists of two potentially
      oscillating subsystems: a spike generator and a subthreshold oscillator. With
      addition of noise the model successfully mimics the major types of experimentally
      recorded impulse patterns and thereby elucidate different resonance behaviors.
      (1) There is a range of rhythmic spiking or bursting where the spike generator is
      strongly coupled to the subthreshold oscillator. (2) There is a pacemaker
      activity of more complex interactions where the spike generator has overtaken
      part of the control. (3) There is a situation where the two subsystems are
      decoupled and only resonate with the help of noise.

PMID- 14568206
TI  - Response kinetics of tethered bacteria to stepwise changes in nutrient
      concentration.
AB  - We examined the changes in swimming behaviour of the bacterium Rhodobacter
      sphaeroides in response to stepwise changes in a nutrient (propionate), following
      the pre-stimulus motion, the initial response and the adaptation to the sustained
      concentration of the chemical. This was carried out by tethering motile cells by
      their flagella to glass slides and following the rotational behaviour of their
      cell bodies in response to the nutrient change. Computerised motion analysis was
      used to analyse the behaviour. Distributions of run and stop times were obtained
      from rotation data for tethered cells. Exponential and Weibull fits for these
      distributions, and variability in individual responses are discussed. In terms of
      parameters derived from the run and stop time distributions, we compare the
      responses to stepwise changes in the nutrient concentration and the long-term
      behaviour of 84 cells under 12 propionate concentration levels from 1 nM to 25
      mM. We discuss traditional assumptions for the random walk approximation to
      bacterial swimming and compare them with the observed R. sphaeroides motile
      behaviour.

PMID- 14568207
TI  - A qualitative model of a motor circadian rhythm.
AB  - In Nature it is possible to observe diverse rhythms. Because of their adaptive
      characteristics, the circadian rhythms are of major importance and have been the
      subject of numerous experimental and theoretical studies. In this article, we
      give a presentation of the main results we have obtained about the motor
      circadian rhythm along some years of collaboration between biologists and
      mathematicians. We present a mathematical model simulating changes in frequency,
      synchronization and amplitude of the circadian oscillation during two
      developmental stages of the crayfish, namely, the juvenile and the adult stages.
      We report also some work in progress on the simulation of the phase response
      curve and on a simplified model of the rhythm.

PMID- 14568208
TI  - Reentrant waves in a ring of embryonic chick ventricular cells imaged with a Ca2+
      sensitive dye.
AB  - According to the classic model initially formulated by Mines, reentrant cardiac
      arrhythmias may be associated with waves circulating in a ring geometry. This
      study was designed to study the dynamics of reentry in a ring geometry of cardiac
      tissue culture. Reentrant calcium waves in rings of cultured embryonic chick
      cardiac myocytes were imaged using a macroscope to monitor the fluorescence of
      intracellular Calcium Green-1 dye. The rings displayed a variety of stable
      rhythms including pacemaker activity and spontaneous reentry. Waves originating
      from a localized pacemaker could lead to reentry as a consequence of
      unidirectional block. In addition, more complex patterns were observed due to the
      interactions between reentrant and pacemaker rhythms. These rhythms included
      instances in which pacemakers accelerated the reentrant rhythm, and instances in
      which the excitation was blocked in the vicinity of pacemakers. During reentrant
      activity an appropriately timed electrical stimulus could induce resetting of
      activity or cause complete annihilation of the propagating waves. This
      experimental preparation reveals many spontaneously occuring complex rhythms.
      These complex rhythms are hypothesized to reflect interactions between
      spontaneous pacemakers, wave propagation, refractory period, and overdrive
      suppression. This preparation may serve as a useful model system to further
      investigate complex dynamics arising during reentrant rhythms in cardiac tissue.

PMID- 14568209
TI  - Clustering huge data sets for parametric PET imaging.
AB  - A new preprocessing clustering technique for quantification of kinetic PET data
      is presented. A two-stage clustering process, which combines a precluster and a
      classic hierarchical cluster analysis, provides data which are clustered
      according to a distance measure between time activity curves (TACs). The
      resulting clustered mean TACs can be used directly for estimation of kinetic
      parameters at the cluster level, or to span a vector space that is used for
      subsequent estimation of voxel level kinetics. The introduction of preclustering
      significantly reduces the overall time for clustering of multiframe kinetic data.
      The efficiency and superiority of the preclustering scheme combined with
      thresholding is validated by comparison of the results for clustering both with
      and without preclustering for FDG-PET brain data of 13 healthy subjects.

PMID- 14568210
TI  - Mechanical analyses of morphological and topological transformation of liposomes.
AB  - Liposomes are micro-compartments made of lipid bilayer membranes possessing the
      characteristics quite similar to those of biological membranes. To form
      artificial cell-like structures, we made liposomes that contained subunit
      proteins of cytoskeletons: tubulin or actin. Spherical liposomes were transformed
      into bipolar or cell-like shapes by mechanical forces generated by the
      polymerization of encapsulated subunits of microtubules. On the other hand, disk-
      or dumbbell-shaped liposomes were developed by the polymerization of encapsulated
      actin. Dynamic processes of morphological transformations of liposomes were
      visualized by high intensity dark-field light microscopy. Topological changes,
      such as fusion and division of membrane vesicles, play an essential role in
      cellular activities. To investigate the mechanism of these processes, we
      visualized the liposomes undergoing topological transformation in real time. A
      variety of novel topological transformations were found, including the opening-up
      of liposomes and the direct expulsion of inner vesicles.

PMID- 14568211
TI  - Stochastic properties of actomyosin motor.
AB  - The epoch-making techniques for manipulating a single myosin molecule have
      recently been developed, and the unitary mechanical reactions of a single
      actomyosin, muscle motor molecule, are directly measured. The data show that the
      unitary mechanical step during sliding along an actin filament of approximately
      5.5 nm, but groups of two to five rapid steps in succession produce displacements
      of approximately 11-30 nm. The instances of multiple stepping are produced by
      single myosin heads during one biochemical cycle of ATP hydrolysis. Thus, the
      coupling between ATP hydrolysis cycle and mechanical step is variable, i.e. loose
      coupling. Such a unique operation of actomyosin molecules is different from that
      of man-made machines, and most likely explains the flexible and effective
      mechanisms of molecular machines in the biosystems.

PMID- 14568212
TI  - Technologies to support the creation of complex systems models--using StarLogo
      software with students.
AB  - Research on complex, adaptive systems has made significant advances in recent
      years in the study of natural and social phenomena that exhibit random variation
      and selection, resulting in learning or evolution. Unfortunately, students
      (including K-12, undergraduate and graduate) in most biology programs have little
      opportunity to explore complex systems during the course of their studies.
      StarLogo and the Adventures in Modeling Curriculum [Adventures in Modeling:
      Exploring Complex, Dynamic Systems with StarLogo. Teachers College Press, New
      York] provide an easily accessible entry point into complex systems modeling for
      students and other novice modelers. These specialized tools can provide powerful
      insights into the dynamics of systems and create opportunities to explore
      challenging and meaningful domains in the biological sciences. Specific
      applications to epidemiological and ecological systems are explored, including
      the often debated topic of the evolution of reduced attack rates in predator-prey
      systems.

PMID- 14568213
TI  - Role of heterogeneity in deterministic models of drug dissolution and their
      statistical characteristics.
AB  - Dissolution of drugs is one of the crucial factors determining their global
      action in a body, and thus for any new solid dosage form its dissolution
      characteristics have to be established. A variety of empirical and semi-empirical
      models for drug dissolution is reviewed in this article. Their properties are
      investigated, the parameters are discussed and the role of drug heterogeneity is
      studied.

PMID- 14568214
TI  - Neural modeling in cerebral dynamics.
AB  - For many years our current conception of neural modeling at cortical level has
      been marked by three convictions: (i) the representational, explanatory, and
      predictive capabilities of a model are always limited by the mathematical nature
      of the formal tools used in its formulation. The external observer in fact
      injects the additional knowledge, apparently resident in the model. (ii) The
      analogical and logical languages (and consequently, the neurophysiological data
      which serves as their basis) are not sufficient to describe, model and predict
      the most genuine aspects of the cortical determined behavior. (iii) We need new
      conceptual and formal tools capable of representing cooperative processes (not
      only physical interactions) in cerebral dynamics. In this paper, we use the
      neuropsychological findings on the residual function after traumatic and surgical
      lesions in animals and men, to think about the sort of requirements that are
      necessary to build these formal tools adequate to model neural information
      processing at cortical level. If we search for inspiration in the field of
      computation, we arrive to the conjecture that the cerebral dynamics is a dynamics
      of neurophysiological symbols and, consequently, we need a set of descriptions at
      an intermediate level (neural assemblies "programming"), in a similar way as we
      use programming languages at an intermediate level (the symbol level) between the
      physical machine and the knowledge level descriptions, in the sense of Newell and
      Marr.

PMID- 14568215
TI  - Single molecule processes on the stepwise movement of ATP-driven molecular
      motors.
AB  - Movement is a fundamental characteristic of all living things. This biogenic
      function that is attributed to the molecular motors such as kinesin, dynein and
      myosin. Molecular motors generate forces by using chemical energy derived from
      the hydrolysis reaction of ATP molecules. Despite a large number of studies on
      this topic, the chemomechanical energy transduction mechanism is still unsolved.
      In this study, we have investigated the chemomechanical coupling of the ATPase
      cycle to the mechanical events of the molecular motor kinesin using single
      molecule detection (SMD) techniques. The SMD techniques allowed to detection of
      the movement of single kinesin molecules along a microtubule and showed that
      kinesin steps mainly in the forward direction, but occasionally in the backward.
      The stepping direction is determined by a certain load-dependent process, on
      which the stochastic behavior is well characterized by Feynman's thermal ratchet
      model. The driving force of the stepwise movement is essentially Brownian motion,
      but it is biased in the forward direction by using the free energy released from
      the hydrolysis of ATP.

PMID- 14568216
TI  - Excitability of the Clay model for squid giant axon.
AB  - The squid giant axon is the canonical experimental membrane prototype for the
      study of action potential generation. This work is concerned with Clay's model
      for this preparation, which implements the nonlinear dependence of sodium and
      potassium currents on voltage, a multicompartmental description of sodium channel
      kinetics that takes into account the dependence between activation and
      inactivation, revised potassium activation function, and potassium accumulation
      in the axoplasm and its uptake by glial cells. This model accounts better than
      the standard Hodgkin-Huxley (HH) model for the response of squid giant axons to
      various stimuli. We systematically compare the responses of the Clay model and
      the standard HH model to pulse-like and constant current stimuli. We also analyze
      hybrid models that combine features from both models. These studies reveal that
      the differences between the sodium currents account for the main difference
      between the two models, namely the lower excitability of the Clay model.

PMID- 14568217
TI  - Electric images of two low resistance objects in weakly electric fish.
AB  - Electroreceptive fish detect nearby objects by processing the information
      contained in the pattern of electric currents through their skin. In weakly
      electric fish, these currents arise from a self-generated field (the electric
      organ discharge), depending on the electrical properties of the surrounding
      medium. The electric image can be defined as the pattern of transepidermal
      voltage distributed over the receptive surface. To understand electrolocation it
      is necessary to know how electric image of objects are generated. In pulse
      mormyrids, the electric organ is localized at the tail, far from the receptors
      and fires a short biphasic pulse. Consequently, if all the elements in the
      environment are resistive, the stimulus at every point on the skin has the same
      waveform. Then, any measure of the amplitude (for example, the peak to peak
      amplitude) could be the unique parameter of the stimulus at any point of the
      skin. We have developed a model to calculate the image, corroborating that images
      are spread over the whole sensory surface and have an opposite center-surround,
      "Mexican-hat" shape. As a consequence, the images of different objects
      superimpose. We show theoretically and by simulation that the image of a pair of
      objects is not the simple addition of the individual images of these objects.

PMID- 14568218
TI  - A chemically driven fluctuating ratchet model for actomyosin interaction.
AB  - With reference to the experimental observations by Yanagida and his co-workers on
      actomyosin interaction, a Brownian motor of fluctuating ratchet kind is designed
      with the aim to describe the interaction between a Myosin II head and a
      neighboring actin filament. Our motor combines the dynamics of the myosin head
      with a chemical external system related to the ATP cycle, whose role is to
      provide the energy supply necessary to bias the motion. Analytical expressions
      for the duration of the ATP cycle, for the Gibbs free energy and for the net
      displacement of the myosin head are obtained. Finally, by exploiting a method due
      to Sekimoto [J. Phys. Soc. Jpn. 66 (1997) 1234], a formula is worked out for the
      amount of energy consumed during the ATP cycle.

PMID- 14568219
TI  - Neuroinformatics Research for Vision Science: NRV project.
AB  - The NRV project (Neuroinformatics Research for Vision Science) is the first
      project in Japan started in 1999 under the Science and Technology Agency of
      Japan, aimed at building the foundation of neuroinformatics research. Because of
      the wealth of data on the visual system, the NRV project will use vision research
      to promote experimental, theoretical and technical research as a pilot study on
      neuroinformatics. Details can be found at: http://www.neuroinformatics.gr.jp/.

PMID- 14568220
TI  - Stochastic fluctuations of the quantal EPSC amplitude in computer simulated
      excitatory synapses of hippocampus.
AB  - The postsynaptic response in glutamatergic synapses of hippocampus, produced by
      the release of a single presynaptic vesicle, shows a large variability in
      amplitude not only among the synapses, but also for a single synapse. A
      mathematical modelling based on a Brownian motion for the diffusion of glutamate
      molecules and receptor binding was applied to study the possible sources of the
      quantal variability. Detailed, geometric and functional, descriptions of the
      vesicle, of the fusion pore and of the synaptic cleft were used and quantal (or
      miniature) EPSCs were computed. Our results show non-saturation of AMPA
      receptors, attributable to the small number of molecules contained in the
      glutamate vesicles of hippocampus. NMDA receptor saturation was obtained rarely,
      only in very specific instances. We concluded that the lack of AMPA saturation
      and intrinsic random variations in basic presynaptic elements, such as the
      vesicle volume and the vesicle docking position, are the main causes of the
      observed stochastic variability of the quantal EPSC amplitude. Only minor effects
      can be ascribed to postsynaptic sources.

PMID- 14568221
TI  - Computer simulation of inhibition-dependent binding in a neural network.
AB  - Reverberating dynamics of neural network is modeled on PC in order to illustrate
      possible role of inhibition as binding controller in the network. The network is
      composed of binding neurons. In the binding neuron model [BioSystems 48 (1998)
      263], the degree of temporal coherence between synaptic inputs is decisive for
      triggering, and slow inhibition is expressed in terms of the degree, which is
      necessary for triggering. Two learning mechanisms are implemented in the network,
      namely, adjusting synaptic strength and/or propagation delays. By means of forced
      playing of external pattern, the network is taught to support dynamics with
      disconnected and bound patterns of activity. By choosing either high, or low
      inhibition, one can switch between the disconnected and bound patterns,
      respectively. This is interpreted as inhibition-controlled binding in the
      network.

PMID- 14568222
TI  - Forward propagating reinforcement learning--biologically plausible learning
      method for multi-layer networks.
AB  - We introduce a biologically plausible method of implementing reinforcement
      learning to multi-layer neural networks. The key idea is to spatially localize
      the synaptic modulation induced by reinforcement signals, proceeding downstream
      from the initial layer to the final layer. Since reinforcement signals are known
      to be broadcast signals in the actual brain, we need two key assumptions,
      inhibitory backward connections and bypass to output units, to spatially localize
      the effect of delayed reinforcement without breaking the basic laws of
      neurophysiology.

PMID- 14568223
TI  - Phase reset and dynamic stability during human gait.
AB  - The human walking movement shows transient changes in response to single short
      lived external perturbations, termed "stumbling reactions." During the stumbling
      reactions, the walking phase is reset. It has been considered that the reactions
      contribute to stabilizing the motion, but less evidence bridging between the
      rhythm reset and the dynamic stability of the gait has been provided. The present
      study tries to establish the relationship between them. To this end, we construct
      a simple dynamical system model of the human musculo-skeletal system interacting
      with the ground, whose joint kinematics during walking is constrained by a given
      periodic joint-angles-profile. We show first that the model can exhibit a stable
      limit cycle corresponding to the steady walking with no perturbations. The
      responses of the limit cycle oscillation are examined by applying a type of
      perturbations at various timings with various intensities, elucidating the
      stability of the model's walking when no phase reset is performed. We then
      observe that modifications of the periodic joint-angles-profile within a short
      time interval in response to the perturbation can alter the responses of the
      limit cycle oscillation and induce phase reset of the model's walking. It is
      shown that appropriate amounts of the phase reset can prevent the model from
      falling, even for the perturbation that induces falling in the case without the
      phase reset. This suggests that those phase resets can improve the dynamic
      stability of the gait. Moreover, the appropriate phase resets predicted by the
      model are compared with the experimentally observed phase resets during human
      stumbling reaction to show they share similar characteristics.

PMID- 14568225
TI  - Phytosterols in the prevention of human pathologies.
AB  - Coronary heart disease is a major health problem in developed countries. Many
      studies have shown that elevated serum concentrations of total or low-density
      lipoprotein cholesterol (LDL cholesterol) are high risk factors, whereas high
      concentrations of high-density-lipoprotein cholesterol (HDL cholesterol) or a low
      LDL to HDL cholesterol ratio may protect against coronary heart disease. Plant
      sterols and stanols derived from vegetable oils or wood pulp have been shown to
      lower total and LDL cholesterol levels in humans by inhibiting cholesterol
      absorption from the intestine. These findings may lead to new therapeutic options
      to treat hypercholesterolemia. In addition, phytosterols may influence cell
      growth and apoptosis of tumor cells. However, they can interfere with the
      absorption of fat soluble vitamins and carotenoids.

PMID- 14568224
TI  - Stochastic processes in nano-biomachines revealed by single molecule detection.
AB  - Proteins and their assemblies are in the size of nanometers and are exposed to
      thermal disturbances. Many molecular processes in these nano-biomachines are
      stochastic, reflecting the fact that the input energy level is comparable to that
      of thermal energy. These stochastic properties have been revealed by recently
      developed single molecule detection techniques. The movement of molecular motors,
      myosin, and kinesin, has been suggested to be thermally driven. Random thermal
      movement is biased using the energy of the ATP hydrolysis. Thus, the molecular
      motors may harness thermal energy. This unique mechanism may be important in
      understanding the operation of the biosystems.

PMID- 14568226
TI  - Pure red cell aplasia--a rare disease with multiple causes.
AB  - Pure red cell aplasia (PRCA) is a relatively rare disease although multiple
      factors are implied in the pathogenesis of its development. A slow progressive
      normocytic-normochromic anemia and reticulocytopenia, without leukopenia and
      thrombocytopenia in a patient who, except pallor, does not show abnormal findings
      on physical examination, should arise the suspicion that he has PRCA. Search for
      underlying diseases or infections and intake of drugs may help for the
      establishment of the diagnosis of acquired PRCA. Lack of erythroblasts in the
      bone marrow with normal development of the other hemopoietic series, as well as
      high level of serum erythropoietin are important clues for the diagnosis.
      Elimination of potentially causative factors, administration of immunosuppressive
      agents and/or recombinant erythropoietin, preferably epoetin beta, may induce
      remission and complete recovery.

PMID- 14568227
TI  - Genes commonly upregulated by hypoxia in human breast cancer cells MCF-7 and MDA
      MB-231.
AB  - Hypoxia is a stress that causes alterations in signal transduction and gene
      instability. In the cancer microenvironment, hypoxia plays a significant role in
      forming a tumor phenotype and tumor progression. We aimed to identify the genes
      upregulated by hypoxia in human breast cancer cell lines, a hormone-dependent MCF
      7 and a hormone-independent MDA-MB-231, using microarray analysis. These cells
      were exposed to two oxygen concentrations such as 21% and 1% in a time-course.
      Out of 12625 genes, 26 genes were identified as commonly upregulated in both MCF
      7 and MDA-MB-231 cells. Some of these genes were already reported as hypoxia
      related, but some of those were identified newly. These commonly upregulated
      genes between hormone-dependent and hormone-independent cells would be a clue to
      study hypoxia-related events and to explore the novel therapeutic targets in
      human breast cancer.

PMID- 14568228
TI  - Induction of insulin production in rat pancreatic acinar carcinoma cells by
      conophylline.
AB  - We set up a screening system to detect low-molecular-weight compounds that induce
      insulin expression in pancreatic acinar carcinoma AR42J cells. They can
      differentiate into insulin-producing cells with neuron-like morphological change
      when treated with activin A. We employed this morphological change for the
      screening of beta-cell inducers among various signal transduction inhibitors. As
      a result, a vinca alkaloid, conophylline, induced neurite formation at 0.1
      approximately 0.3 microg/ml in 72 h, like activin A. Conophylline-treated cells
      were found to express insulin as measured at both mRNA and protein levels. By RT
      PCR analysis, conophylline-treated cells were shown to express neurogenin3
      strongly. They also expressed Beta2/NeuroD and Nkx2.2, but not Pax4 and PP.
      Although activin A induces nuclear translocation of Smad2, conophylline did not.
      But the latter induced p38 activation, like activin A, as detected by
      phosphorylation. Pretreatment with a p38-specific inhibitor, SB203580, lowered
      the conophylline-induced insulin production. Therefore, p38 activation would be
      involved in the differentiation of AR42J cells into insulin-producing cells.
      Studies on structure-activity relationship with conophyllidine, conofoline,
      conophyllinine, and related monomer alkaloids showed that the dimeric
      aspidosperma structure with the dihydrofuran unit in its center was essential for
      the differentiation-inducing activity.

PMID- 14568229
TI  - Dynorphin-A(1-17) decreases nitric oxide release and cytotoxicity induced with
      lipopolysaccharide plus interferon-gamma in murine macrophage cell line J774.
AB  - Nitric oxide (NO) is an important mediator of cytotoxicity caused by macrophages
      or by their resident counterpart in brain-glial cells. Modulation of NO release
      by both activated macrophages and glial cells has been reported in the presence
      of endogenous (peptide) and synthetic (non-peptide) agonists with kappa opioid
      receptors (KOR) selectivity. The data obtained with macrophages and glial cells
      are contradictory: enhanced NO release by mouse macrophages was reported in the
      presence of synthetic agonist of KOR selectivity (Neuropeptides 32 (1998) 287),
      and decreased NO release by glial cells, in the presence of dynorphin-A((1-8)),
      endogenous opioid peptide with KOR selectivity (J. Biomed. Sci. 7 (2000) 241). In
      this study, we used a murine cell line J774 of macrophage origin and examined the
      effect of dynorphin-A((1-17)), endogenous opioid peptide with selectivity for
      KOR, on NO release induced with lipopolysaccharide (LPS) plus interferon-gamma
      (IFN-gamma). Dynorphin-A((1-17)) was chosen since in comparison to dynorphin-A((1
      13)), it is more resistant to biodegradation (Peptides 17 (1996) 983), and its
      effects during prolonged treatment of cells could be more pronounced. The effect
      of dynorphin-A((1-17)) on NO release was compared to its effect on cytotoxicity,
      induced with LPS plus IFN-gamma. The data obtained have shown that activation
      induced NO release by J774 cells is decreased in the presence of dynorphin-A((1
      17)). This was associated with deceased LPS and IFN-gamma-induced cytotoxicity of
      J774 cells, suggesting their causal relationship. Neither of the observed effects
      of dynorphin-A((1-17)) could be prevented with the KOR selective antagonist,
      norbinaltorphimine, suggesting that they are mediated via non-opioid mechanism.
      By diminishing NO release dynorphin-A((1-17)) may affect cytotoxic ability of
      macrophages, but may also beneficially influence inflammation-induced damage of
      local tissue.

PMID- 14568230
TI  - Effects of alatrofloxacin, the parental prodrug of trovafloxacin, on phagocytic,
      anti-inflammatory and immunomodulation events of human THP-1 monocytes.
AB  - Alatrofloxacin functions similar to other fluoroquinolone antibiotics in that it
      not only has antibiotic activity to kill invading organisms by interfering with
      DNA synthesis, it possesses immunosuppressive activity. In the first hour after
      bacteria have been phagocytosed by THP-1 monocytes, the drug activates a lytic
      mechanism involving the release of c-AMP, tumor necrosis factor (TNFalpha),
      interleukin-1 (IL-1), IL-6 and nitric oxide, with elevations in lysosomal
      hydrolytic enzyme activities. This effect reverses between 2 and 4 h. At this
      time, all of these inflammatory processes are returned to normal values or below
      suggesting that alatrofloxacin reduces the spread of infection and destruction of
      tissue related to inflammation.

PMID- 14568231
TI  - Cytokine secretion in nasal mucus of normal subjects and patients with allergic
      rhinitis.
AB  - Allergic rhinitis is regulated by the local production and release of several
      cytokines. The levels of Th2 cytokines IL-4, IL-6, IL-10 and the Th1 cytokine IFN
      gamma were studied in nasal mucus from 30 subjects with allergic rhinitis and 45
      non-atopic healthy controls. In this study a sampling technique for collecting
      nasal mucus, well tolerated by the subjects and with a minimal stimulation of the
      mucosa, was performed. The cytokine concentrations in nasal mucus samples were
      detected and quantitated by a new paramagnetic particle-based immunofluorescent
      assay system more sensitive than the conventional ELISA techniques. The new
      technique showed reliable values of the measured parameters. The nasal mucus from
      allergic patients contained significantly higher concentrations of IL-4 (25.5 +/-
      3.6 pg/ml; P < 0.001) and IL-10 (1300 +/- 190 pg/ml; P < 0.05) compared to the
      nasal mucus from control subjects (15.2 +/- 2.3 and 532 +/- 28 pg/ml,
      respectively, for IL-4 and IL-10). No significant modification in IFN-gamma
      levels of allergic patients was found when compared to control group
      (respectively, 19.9 +/- 3.3 vs. 25.7 +/- 5.1 pg/ml; P > 0.05). Moreover, the
      allergic patients showed lower levels of IL-6 concentrations in the nasal mucus
      compared to control subjects (64.8 +/- 9.1 vs. 129.0 +/- 18.1 pg/ml; P = 0.0099).
      These data can be interpreted by the hypothesis that in response to environmental
      allergens there is a preferential Th2 polarity by activated CD4+ T cells and that
      the cytokines IL-6 and IL-10 have, respectively, an important anti-inflammatory
      and counterregulatory action in the pathogenesis of allergic rhinitis.

PMID- 14568232
TI  - Significant association of HLA A2-DR11 with CD4 naive decrease in autistic
      children.
AB  - Nine autistic children and 37 ethnically homogenous controls were enrolled in the
      study to assess their human leukocyte antigen (HLA) pattern, and eight healthy
      children were studied to define their peripheral blood cell subsets. We observed
      a significant decrease in CD4+ naive and an increase in CD4+ memory T cells in
      autistic children. These differences were significantly more pronounced in the
      autistic children bearing the HLA A2 and DR11 alleles. These data support the
      hypothesis that autism could be due to an immune imbalance occurring in
      genetically predisposed children.

PMID- 14568233
TI  - Medical ethics and the call for transparency.

PMID- 14568235
TI  - NMR spectroscopy of Group 13 metal ions: biologically relevant aspects.
AB  - In spite of the fact that Group 13 metal ions (Al(3+), Ga(3+), In(3+) and
      Tl(+/3+)) show no main biological role, they are NMR-active nuclides which can be
      used in magnetic resonance spectroscopy of biologically relevant systems. The
      fact that these metal ions are quadrupolar (with the exception of thallium) means
      that they are particularly sensitive to ligand type and coordination geometry.
      The line width of the NMR signals of their complexes shows a strong dependence on
      the symmetry of coordination, which constitutes an effective tool in the
      elucidation of structures. Here we report published NMR studies of this family of
      elements, applied to systems of biological importance. Special emphasis is given
      to binding studies of these cations to biological molecules, such as proteins,
      and to chelating agents of radiopharmaceutical interest. The possibility of in
      vivo NMR studies is also stressed, with extension to (27)Al-based MRI (magnetic
      resonance imaging) experiments.

PMID- 14568236
TI  - Toxic and biochemical effects of zinc in Caco-2 cells.
AB  - Zinc (in relatively high concentrations) can be toxic to intestinal cells. The
      aim of the present study was to quanitfy cellular injury in preconfluent, colonic
      cancerous cells and in postconfluent, differentiating human intestinal Caco-2
      cells. Cellular damage was measured by using cell proliferation, lactate
      dehydrogenase (LDH)-release, and apoptosis studies. Furthermore, the activities
      of the major antioxidative enzymes [superoxide dismutase (SOD), glutathione
      peroxidase (GPx) and catalase] and differentiation markers (alkaline phosphatase
      and aminopeptidase-N) were determined after exposure of the cells to increasing
      amounts of zinc sulfate. Proliferation and viability decreased in a concentration
      dependent manner. A noticeable increase of LDH-release correlated to cell
      rounding and detachment at relatively high zinc levels (200 muM) was observed in
      both groups of cells. Above 100 muM of zinc, significant apoptotic activity was
      found in the preconfluent cells. Zinc supplementation did not alter SOD
      activities. However, GPx and, in part, catalase activities tended to be higher in
      zinc-treated cells (nevertheless the results were not significant).
      Differentiation markers were noticeably induced by increasing amounts of zinc,
      especially in the preconfluent cells. In conclusion, we suggest that the
      susceptibility to zinc induced damage is equal in both confluentation groups of
      Caco-2 cells. Risk assessment for high concentrations seems recommendable.

PMID- 14568237
TI  - The reaction of allyl and benzylarsonic acids with thiols: mechanistic aspects
      and implications for dioxygen activation by trivalent arsenic compounds.
AB  - The reaction of allyl and benzylarsonic acids with thiophenol gives not only the
      expected diphenyl alkyldithioarsonites and diphenyl disulfide but also various
      other compounds arising from the decomposition at the arsenic(V) oxidation level
      (the arsonic acids) by thiophenol and at the arsenic(III) oxidation level (mainly
      the alkyldithioarsonites) by thiophenol and by dissolved dioxygen. The reaction
      of these arsonic acids with 4-nitrothiophenol, which is not oxidized by dioxygen,
      revealed that the arsenic(III) of these alkyldithioarsonites is the active atom
      towards dioxygen. However, the reaction of allyl, benzyl, and 2-picolylarsonic
      acids with DL-penicillamine gives the expected products with no or very small
      oxidative decomposition. The decomposition pathways of allyl and benzylarsonic
      acids were elucidated. The results are briefly discussed in the contexts of the
      use of arsonic acids in chemotherapy and the ability of arsenic(III) compounds to
      generate reactive oxygen species.

PMID- 14568238
TI  - Adenine-copper coordination polymer as an oxidative nucleozyme: implications for
      simple prebiotic catalytic units.
AB  - Plasmid modification activity of a modified adenine-copper coordination polymer,
      in the presence of peracids and thiols, and ensuing preliminary mechanistic
      investigations are reported. These observations, when coupled with unique
      coordination pattern of the metal complex, have led us to propose that a
      synergistic interaction between nucleobases and metal ions may be responsible for
      primordial catalysis of certain key reactions of biochemical significance and
      could serve the function of a prototypical, prebiotic nucleozyme.

PMID- 14568239
TI  - Iminodiacetyl-hydroxamate derivatives as metalloproteinase inhibitors:
      equilibrium complexation studies with Cu(II), Zn(II) and Ni(II).
AB  - Two new iminodiacetyl-hydroxamate derivatives, the N-benzyl-N-carboxymethyl
      iminoacetohydroxamic acid (H(2)L(1)) and the N-benzyl-N'-hydroxypiperazine-2,6
      dione (HL(2)), have been recently reported as very effective inhibitors against a
      set of zinc-containing matrix metalloproteinases (MMPs). Herein, aimed at
      understanding that inhibitory function, these compounds are studied in their
      complex formation equilibria with three biologically relevant first-row
      transition M(2+) metal ions (M=Cu, Zn, Ni) by using potentiometric and
      spectroscopic techniques. At physiological conditions, complexation of these
      metal ions by H(2)L(1) mostly occurs with formation of 1:1 species by tridentate
      co-ordination (O,N,N) (carboxylate-amino-hydroxamate), whereas complexation with
      HL(2) mainly involves the formation of 1:2 (M:L) species with normal (O,O)
      hydroxamate coordination. Moreover, at higher pH, H(2)L(1) is able to form a
      pentanuclear tetrameric copper complex with an interesting 12-metallacrown-4
      structure.

PMID- 14568240
TI  - The influence of methionine-containing peptides on the reaction of carboplatin
      with 5'-guanosine monophosphate: a comparison with cisplatin.
AB  - The pH- and time-dependent reaction of the anticancer drug carboplatin, [Pt(cbdca
      kappa(2)O,O')(NH(3))(2)] (cbdca=cyclobutane-1,1-dicarboxylate), with the
      tripeptides H-glyglymet-OH (glycylglycyl-L-methionine) and Ac-glyglymet-OH at 313
      K was investigated by high-performance liquid chromatography, NMR and mass
      spectrometry. The relative stability of the initial ring-opened kappaS complex
      [Pt(cbdca-kappaO)(Ac-glyglymet-OH-kappaS)(NH(3))(2)] leads to increased formation
      of the kinetically favoured kappaS:kappaS' bis-adduct [Pt(Ac-glyglymet-OH
      kappaS)(2)(NH(3))(2)](2+) in comparison with cisplatin. As a result a second 1:2
      reaction pathway kappaS-->kappaS:kappaS'-->kappa(2)N(M), S:kappaS'-
      >kappa(3)N(G2),N(M), S:kappaS', where N(M) and N(G2) represent, respectively,
      metallated methionine and glycine nitrogen atoms, competes with the 1:1 route
      kappaS-->kappa(2)N(M), S-->kappa(3)N(G2),N(M), S also observed for cisplatin.
      Cleavage of N-acetylglycine at the backbone C(O)-N bond to the second gly residue
      (G2) is observed after 100 h for the respective tridentate complexes [Pt(Ac
      glyglyH(-1)metH(-1)-OH-kappa(3)N(G2),N(M), S) (Ac-glyglymet-OH-kappaS)] and
      [Pt(Ac-glyglyH(-1)metH(-1)-OH-kappa(3)N(G2),N(M), S)(NH(3))] at pH <5.2. The
      longevity of the initial kappaS complex leads to about an eight-fold increase in
      the rate of formation of the kappaN7:kappaN7' bis-adduct [Pt(5'-GMP
      kappaN7)(2)(NH(3))(2)](2-) for the reaction of carboplatin with 5'-GMP(2-) at pH
      7 in the presence of Ac-glyglymet-OH. A mixed-ligand kappaS:kappaN7 species
      [Pt(5'-GMP-kappaN7)(Ac-glyglymet-OH-kappaS)(NH(3))(2)] provides the major
      precursor for this 1:2 nucleotide complex and kappaN7 coordination of 5'-GMP(2-)
      is also observed in the kappa(2)N(M),S:kappaN7 complex [Pt(5'-GMP-kappaN7)(Ac
      glyglymetH(-1)-OH-kappa(2)N(M),S)(NH(3))(2)](-) formed by substitution of the
      ammine ligand trans to the methionine sulphur. As the intermediate kappaS:kappaN7
      species is formed rapidly within the first 10 h of reaction, these results
      suggest that the transfer reaction pathway kappaS-->kappaS:kappaN7-
      >kappaN7:kappaN7' involving kappaS platinated peptides could play an important
      role in accelerating the rate of DNA binding for carboplatin.

PMID- 14568241
TI  - Synthesis, characterization, DNA binding study and biological activity against
      Leishmania mexicana of [Cu(dppz)2]BF4.
AB  - [Cu(dppz)(2)]BF(4) complex has been synthesized by the reaction of
      [Cu(CH(3)CN)(4)]BF(4) and dipyrido[3,2-A:2',3'-c]phenazine (dppz) in a molar
      ratio of 1:2. The compound was characterized by fast atom bombardment mass
      spectrometry, 1H nuclear magnetic resonance, UV-Vis and IR spectroscopies.
      Absorption and viscometric studies carried out on the interaction of
      [Cu(dppz)(2)]BF(4) complex with calf thymus DNA suggested that the complex binds
      by intercalation. No covalent binding was observed. Additionally, the results
      obtained from electrophoresis showed nuclease activity. The biological activity
      of the complex was tested in vitro on Leishmania mexicana promastigote cultures.
      A leishmanicidal effect (LD(30)) was observed in 48 h at concentration of 41 nM.
      Preliminary studies of the ultrastructure of L. mexicana treated with a sublethal
      dose of the complex (IC(7)=4.1 nM) for 48 h showed an induction of cytoplasm
      disorganization, vacuolization and binucleated cells. These findings suggest that
      the leishmanicidal activity of the title complex could be associated with its
      interaction with the parasitic DNA.

PMID- 14568242
TI  - Characterization of diorganotin(IV) complexes with captopril. The first
      crystallographically authenticated metal complex of this anti-hypertensive agent.
AB  - Diorganotin(IV) complexes R(2)Sn(cap) (capH(2)=N-[(S)-3-mercapto-2
      methylpropionyl]-L-proline; R=Me, Et, n-Bu and t-Bu) were prepared and
      characterised. The FTIR and Raman spectra demonstrated that the organotin(IV)
      moieties interact with the [S] atom of the ligand, while the other coordination
      sites are the carboxylate and the amide -CO groups. Mossbauer Delta data showed
      that the diorganotin(IV) compounds adopt slightly distorted trigonal-bipyramidal
      (tbp) geometry. A single-crystal X-ray study was performed on the compound
      Me(2)Sn(cap): the Sn atom is five-coordinated in a distorted tbp environment,
      with two [O] atoms in the axial positions and the [S] and two [C] atoms in the
      equatorial (eq) plane. Each cap ligand coordinates to two different Sn atoms, and
      infinite zigzag chains are formed, directed parallel to each other and to the b
      axis of the unit cell. NMR (CDCl(3)) of the Me(2)Sn(IV) and n-Bu(2)Sn(IV)
      complexes indicated the presence of different oligomeric species.

PMID- 14568243
TI  - Interfacial molecular recognition between polysaccharides and calcium carbonate
      during crystallization.
AB  - Based on the basic principles of biomineralization, using beta-cyclodextrin,
      hepatin and soluble starch as organic matrices, employing the biomimetic method,
      the crystallization of CaCO(3) was studied by Fourier transform infrared
      spectroscopy (FT-IR), X-ray powder diffraction analysis (XRD), scanning
      electronic microscopy (SEM), thermal gravity-differential thermal analysis and
      conductivity analysis. The results show that polysaccharides have an effect on
      the crystallization of CaCO(3). CaCO(3) crystals also have an effect on
      polysaccharides. The possible mechanism of this interaction is discussed.

PMID- 14568244
TI  - Fluorescent complex of pyoverdin with aluminum.
AB  - When a pyoverdin (PV), (a siderophore) from Pseudomonas fluorescens, binds
      aluminum 1:1, its natural fluorescence almost doubles, whereas PV-Fe is non
      fluorescent. Complex formation allows [Al] determination down to 1 mug/l. Fe(III)
      in the sample interferes with [Al] determination, but added after PV, improves
      the assay's performance. Ascorbic acid does not eliminate Fe(III) interference.
      PV-Al fluorescence could have analytical and toxicological applications.

PMID- 14568246
TI  - Immunosuppressive therapy in liver transplantation.

PMID- 14568247
TI  - Hemopoietic progenitor cells and bone marrow stromal cells in patients with
      autoimmune hepatitis type 1 and primary biliary cirrhosis.
AB  - BACKGROUND/AIMS: Autologous hematopoietic stem cell transplantation has been used
      in severe cases of autoimmunity. We investigated whether hemopoietic progenitor
      cells and/or bone marrow (BM) microenvironment are affected in autoimmune
      hepatitis type-1 (AIH-1) and primary biliary cirrhosis (PBC). METHODS: We studied
      13 AIH-1 patients, 13 PBC patients, 12 cirrhotic controls (CC) and ten healthy
      controls (HC). Flow cytometry, expansion cultures, long-term BM cultures and
      clonogenic progenitor cell assays were used. Stromal cell function was assessed
      in long-term BM cultures recharged with normal CD34+ cells. RESULTS: AIH-1 had
      increased CD34+, CD34+/CD38+ and CD34+/CD38- cells compared to all groups
      (P<0.001). PBC had lower progenitor cells compared to controls (P<0.005). No
      differences were found between CC and HC. Committed progenitor cells in non
      adherent cell fraction were increased in AIH-1 (P<0.05) but decreased in PBC
      compared to controls (P<0.05). Granulocyte-macrophage colony forming units (CFU)
      and erythroid-burst CFU were increased in AIH-1 compared to all groups (P<0.001).
      PBC had these CFUs decreased compared to controls (P<0.005). Stromal cells failed
      to support normal hemopoiesis in PBC. CONCLUSIONS: We demonstrated for the first
      time that AIH-1 had increased hemopoietic progenitor cells and normal stromal
      function. In PBC, progenitor cells and BM microenvironment were defective.
      Further studies will determine the significance of these novel findings.

PMID- 14568248
TI  - Hepatic artery malformations associated with a primary defect in intrahepatic
      bile duct development.
AB  - BACKGROUND/AIMS: The portal tracts contain bile ducts associated with branches of
      the portal vein and of the hepatic artery. Hepatic artery malformations are found
      in diseases in which fetal biliary structures persist after birth (ductal plate
      malformations). Here we investigated how hepatic artery malformations relate to
      abnormal bile duct development. METHODS: Hepatic artery and biliary development
      was analyzed in fetuses with Jeune syndrome or Meckel syndrome, which show ductal
      plate malformations. We also analyzed hepatic artery development in transgenic
      mice which exhibit biliary anomalies following inactivation of the genes for
      hepatocyte nuclear factor (HNF)-6 or HNF-1beta, two transcription factors
      expressed in biliary cells, but not in arteries. RESULTS: We show that arterial
      anomalies occurred in fetuses with Jeune syndrome or Meckel syndrome. We provide
      the first description of hepatic artery branch development in the mouse and show
      that inactivation of the Hnf6 or Hnf1beta gene results in anomalies of the
      hepatic artery branches. In the transgenic mice and in the human syndromes, the
      biliary anomalies preceded the arterial anomalies. CONCLUSIONS: A primary defect
      in biliary epithelial cells is associated with hepatic artery malformations in
      mice. Our data provide a model to interpret and study hepatic artery anomalies in
      humans.

PMID- 14568249
TI  - Changes in the expression and localization of hepatocellular transporters and
      radixin in primary biliary cirrhosis.
AB  - BACKGROUND/AIMS: Expression and localization of human hepatocellular transporters
      and of radixin, cross-linking actin with some membrane transporters, may change
      in cholestatic liver diseases. METHODS: We investigated the uptake transporters
      OATP2 (SLC21A6), OATP8 (SLC21A8), and NTCP (SLC10A1), the export pumps MRP2
      (ABCC2), MRP3 (ABCC3), MRP6 (ABCC6), and P-glycoproteins (ABCB1, ABCB4, ABCB11),
      and radixin, in non-icteric primary biliary cirrhosis (PBC stages I-III) and
      control human liver needle-biopsies using immunofluorescence microscopy and semi
      quantitative RT-PCR. RESULTS: Expression and localization of all transporters
      were unchanged in PBC I-II. Immunostaining intensities of uptake transporters
      decreased in PBC III with a concomitant decrease in mRNA levels. Immunostaining
      intensities and mRNA levels of export pumps were similar in controls and PBC I
      III, however, irregular MRP2 immunostaining suggested redistribution of MRP2 into
      intracellular structures in PBC III. Areas of irregular MRP2 immunostaining
      showed largely reduced radixin immunostaining, whereas normal hepatocytes had
      MRP2 and radixin confined to the canalicular membrane. Disrupted localization of
      radixin and MRP2 supports the concept that radixin contributes to the canalicular
      localization of MRP2. CONCLUSIONS: Down-regulation of uptake transporters may
      contribute to the impaired hepatobiliary elimination in advanced PBC, and
      partially altered localization of MRP2 may reflect the onset of changes leading
      to icteric PBC.

PMID- 14568250
TI  - The ubiquitously expressed MURR1 protein is absent in canine copper toxicosis.
AB  - BACKGROUND/AIMS: Copper toxicosis (CT) in Bedlington terriers is an autosomal
      recessive disorder characterized by massive lysosomal copper accumulation in
      livers of affected dogs, and a defect in the biliary excretion of this metal. We
      propose that MURR1, the gene defective in canine CT, has a role in the regulation
      of copper excretion into bile during copper overload. METHODS: Polyclonal
      antibodies raised against full-length recombinant human MURR1 were used for
      immunoblot analysis and indirect immunofluorescence studies. RESULTS: Using
      Western blot analysis, these antibodies abundantly detected MURR1 as a 23 kDa
      protein in liver extracts of mice and dogs, but MURR1 was undetectable in the
      livers of affected Bedlington terriers. MURR1 was also detected in different
      tissues and cell lines; in cell lines the protein was found both in cytosol and
      membrane preparations. Consistent with this observation, indirect
      immunofluorescence staining revealed that in some cells MURR1 was associated with
      a vesicular compartment diffusely localized throughout the cell. CONCLUSIONS: The
      genomic deletion in MURR1 results in complete absence of MURR1 protein. Based on
      the unanticipated subcellular localization, our results suggest a role for MURR1
      in the regulation of vesicular copper sequestration during copper overload.

PMID- 14568251
TI  - The role of the iron responsive element in the control of ferroportin1/IREG1/MTP1
      gene expression.
AB  - BACKGROUND/AIMS: MTP1/Ferroportin1/IREG1, the product of the SLC40A1 gene, is a
      main iron export protein in mammals. However, the way this gene is regulated by
      iron is still unclear. The aim of this study was to investigate the functional
      role of genomic SLC40A1 elements in response to iron. METHODS: Vectors containing
      either reverse similar 2.6 kb 5' flanking region or deletion constructs,
      including one devoid of an iron responsive element (SLC40A1-DeltaIRE-Luc), were
      analyzed by luciferase reporter gene in transfected HepG2, CaCO2 and U937 cells.
      Expression of iron genes and activity of the iron regulatory protein were also
      studied. RESULTS: Iron increased and desferrioxamine decreased luciferase
      activity in all the cell types using both the full-length construct and the
      promoter deletion constructs, in the absence of changes in SLC40A1 or luciferase
      mRNA levels. To test the role of the SLC40A1 5' untranslated region, we first
      demonstrated that wild type and not SLC40A1-DeltaIRE-Luc could bind iron
      regulatory protein. Then, in cells transfected with SLC40A1-DeltaIRE-Luc, we
      found that, in spite of iron regulatory protein activation, the response to iron
      manipulation was lost. CONCLUSIONS: We demonstrate that the iron responsive
      element in the SLC40A1 gene is functional and that it controls gene expression
      through the cytoplasmic iron regulatory protein system.

PMID- 14568252
TI  - Rapid formation of hepatic organoid in collagen sponge by rat small hepatocytes
      and hepatic nonparenchymal cells.
AB  - BACKGROUND/AIMS: Hybrid bioartificial liver devices supporting a large mass of
      metabolically active hepatocytes are thought to be necessary for the successful
      treatment of patients with severe acute liver failure. However, it is very
      difficult to obtain cells with both growth activity and differentiated functions.
      Rat small hepatocytes (SHs), which are hepatic progenitor cells, can
      differentiate into mature hepatocytes and reconstruct a hepatic organoid by
      interacting with hepatic nonparenchymal cells (NPCs). METHODS: Colonies of SHs
      were collected and replated on a collagen sponge. Hepatic functions were examined
      by ELISA, immunoblotting, and Northern blotting. Cells in the sponge were
      characterized by immunocytochemistry and transmission electron microscopy. Urea
      synthesis was measured and metabolization of fluorescein diacetate was examined.
      RESULTS: SHs could proliferate and expand to form a hepatic organoid in the
      sponge. Albumin secretion and other hepatic protein production of the cells in
      the sponge increased with time in culture and the amounts were much larger than
      for those obtained from cells grown on dishes. Morphologically and functionally
      differentiated hepatocytes were observed and some CK19-positive cells formed duct
      like structures within the sponge. Excretion of fluorescein was observed in bile
      canaliculi. CONCLUSIONS: Hepatic organoids can be rapidly reconstructed in a
      collagen sponge by rat SHs and NPCs.

PMID- 14568253
TI  - Intrapulmonary vascular dilatation and nitric oxide in hypoxemic rats with
      chronic bile duct ligation.
AB  - BACKGROUND/AIMS: Nitric oxide (NO) has been suggested as the major cause of
      pulmonary vascular dilatation and hypoxemia in hepatopulmonary syndrome (HPS).
      The aim of this study was to assess the effect of NO on arterial oxygenation in
      rats with common bile duct ligation (CBDL rats), a model of HPS. METHODS:
      Arterial blood gases were measured in 44 CBDL rats and 44 Sham rats under
      unrestrained conditions. Intrapulmonary shunting was assessed with (141)Ce
      labeled microspheres (15-mum diameter) and serum nitrate/nitrite levels were
      measured by HPLC. The effect of NOS inhibition on A-aDO(2) was studied using L
      NAME. RESULTS: A decrease of PaO(2) below 82.7 mmHg (the mean value-2sigma in
      Sham rats) was seen in 43% of CBDL rats. Intrapulmonary shunting was greater in
      CBDL rats than in Sham rats (P<0.001). A correlation between the extent of
      shunting and A-aDO(2) was found in all animals studied (r=0.89, P<0.001, n=16).
      Serum levels of nitrate/nitrite increased significantly across the lungs, and the
      increase was significantly correlated with A-aDO(2) in the total population of
      animals studied. Administration of L-NAME to CBDL rats achieved a significant
      improvement of A-aDO(2). CONCLUSIONS: These results suggest that pulmonary
      vascular dilatation due to NO leads to hypoxemia in CBDL rats.

PMID- 14568255
TI  - Three-dimensional reconstruction of hepatic bridging fibrosis in chronic
      hepatitis C viral infection.
AB  - BACKGROUND/AIMS: Fibrosis in chronic hepatitis C infection begins in portal
      tracts, and can progress to 'bridging fibrosis' and eventually lead to cirrhosis.
      All current fibrosis staging systems are based on these three conceptual fibrosis
      stages (portal fibrosis, bridging fibrosis, cirrhosis) and vary only in how these
      stages are further subdivided. Despite the importance of bridging fibrosis,
      little is known about its three-dimensional characteristics. METHODS: Foci of
      bridging fibrosis were digitally reconstructed in three dimensions on two
      separate liver specimens with chronic hepatitis C viral infection. The amount of
      portal fibrosis was then correlated with bile duct diameter on trichrome-stained
      sections. RESULTS: After three-dimensional reconstruction, the bridges were seen
      to represent webs or membranes of fibrosis located at branch points of the portal
      tracts that extended between two portal branches, much like the webbing between
      the thumb and forefinger in a baseball-mitt. Direct measurements indicated that
      early portal fibrosis was associated with portal tracts containing bile ducts of
      approximately 18-19 mum diameter. CONCLUSIONS: Fibrosis bridges are located at
      branch points of portal tracts and are composed of three-dimensional webs or
      membranes that extend between portal tracts; when viewed as two dimensions on a
      glass slide, a 'bridge' of fibrosis is seen.

PMID- 14568254
TI  - Inhibitory effect of a soluble transforming growth factor beta type II receptor
      on the activation of rat hepatic stellate cells in primary culture.
AB  - BACKGROUND/AIMS: Oxidative stress, including the generation of reactive oxygen
      species (ROS) that acts as a signaling mediator for transforming growth factor
      (TGF)-beta, plays a key role in hepatic fibrosis. Hepatic stellate cells (HSCs)
      produce and respond to TGF-beta in an autocrine manner with increased collagen
      expression. It has previously been reported that the adenovirus-mediated
      overexpression of a soluble receptor against the extracellular domain of the TGF
      beta type II receptor prevents hepatofibrogenesis in vivo, although its
      inhibitory role and mechanism in HSC activation remains to be elucidated.
      METHODS: In this study, we report on an examination of the actual role of TGF
      beta inhibition on oxidative stress and the activation of cultured rat HSCs,
      using the adenovirus-mediated soluble TGF-beta type II receptor. RESULTS: This
      soluble receptor secreted from the adenovirus-infected cells binds to TGF-beta.
      Infection of HSCs with this adenovirus attenuated intracellular levels of TGF
      beta1 mRNA and protein, NADH oxidative activity, ROS generation and lipid
      peroxidation, and prevented HSC activation. CONCLUSIONS: These findings suggest
      that this adenovirus-mediated soluble TGF-beta receptor may lead to an
      interruption of the TGF-beta autocrine loop in activated HSC, in part, by
      inhibiting oxidative stress.

PMID- 14568256
TI  - A blocking peptide for transforming growth factor-beta1 activation prevents
      hepatic fibrosis in vivo.
AB  - BACKGROUND/AIMS: Thrombospondin-1 is a major activator of transforming growth
      factor-beta1 (TGF-beta1), and a peptide derived from the latency-associated
      peptide, Leu-Ser-Lys-Leu (LSKL), inhibits the activation of TGF-beta1. In this
      study, the effects of LSKL on the hepatocyte damage and fibrogenesis in
      dimethylnitrosamine (DMN)-induced rat liver fibrosis were examined. METHODS:
      Animals were given an intraperitoneal (i.p.) injection of DMN or saline three
      times per week for 4 weeks, and treated with LSKL, a control peptide, or saline
      i.p. daily. RESULTS: Liver atrophy caused by DMN-injection was significantly
      inhibited in the DMN+LSKL group. The degrees of necrosis/degeneration and
      fibrosis scores were significantly lower in the DMN+LSKL group than in the
      control groups. The hydroxyproline content was significantly higher in the
      control groups than in the DMN+LSKL group. The amount of active TGF-beta1 was
      less in the DMN+LSKL group than in the control groups, and the active/total TGF
      beta1 ratio in the DMN+LSKL group was suppressed in the control groups.
      Phosphorylation of Smad 2 in the liver was significantly decreased in the
      DMN+LSKL group. CONCLUSIONS: The LSKL peptide prevented the progression of
      hepatic damage and fibrosis through the inhibition of TGF-beta1 activation and
      its signal transduction in vivo.

PMID- 14568257
TI  - Carbenoxolone inhibits DNA synthesis and collagen gene expression in rat hepatic
      stellate cells in culture.
AB  - BACKGROUND/AIMS: This study using primary-cultured rat hepatic stellate cells
      (HSCs) was aimed to reveal the effect of carbenoxolone and the other gap-junction
      blockers on the proliferation and activation of HSCs. METHODS: HSC morphology was
      microscopically evaluated. DNA synthesis was determined by [3H]thymidine
      incorporation. Expression of HSC activation markers and cell cycle-related
      proteins was evaluated by Western blot. Collagen alpha1(I) mRNA expression was
      evaluated by quantitative reverse transcription polymerase chain reaction.
      RESULTS: Carbenoxolone triggered the morphological change of activated HSCs
      without inducing apoptosis. Culture-induced DNA synthesis was suppressed to 22.6
      and 8.51%, respectively, by 40 and 80 microM carbenoxolone. The other gap
      junction blockers failed to affect the morphology and the DNA synthesis of
      activated HSCs. Carbenoxolone decreased the expression of cyclins D1/2 and cyclin
      dependent kinases 4/6. Platelet-derived growth factor (PDGF)-BB-elicited DNA
      synthesis was reduced to 45.6 and 3.27%, respectively, by 40 and 80 microM
      carbenoxolone. Phosphorylation of c-Raf, MEK and mitogen-activated protein
      kinase, but not PDGF receptor beta, under PDGF-BB stimulation was attenuated by
      carbenoxolone. Collagen alpha1(I) mRNA expression was significantly reduced. In
      addition, carbenoxolone suppressed the activation process of quiescent HSCs.
      CONCLUSIONS: Carbenoxolone reduced the DNA synthesis and the expression of
      collagen alpha1(I) mRNA in activated HSCs independently of its pharmacological
      action as gap-junction blocker.

PMID- 14568258
TI  - Lipid peroxidation, stellate cell activation and hepatic fibrogenesis in a rat
      model of chronic steatohepatitis.
AB  - BACKGROUND/AIMS: We explored the involvement of cell types, cytokines and lipid
      peroxidation in a rat dietary model of fibrosing steatohepatitis. METHODS: Male
      rats were fed a high fat diet deficient in methionine and choline (MCD) for up to
      17 weeks. Whole liver, hepatocytes and non-parenchymal cells were analysed for
      reduced glutathione (GSH) levels, products of lipid peroxidation (thiobarbituric
      acid reactive substances, TBARS), liver injury, and fibrosis. RESULTS: MCD diet
      fed rats developed hepatic steatosis at week 2 and focal necroinflammatory change
      by week 5, while pericellular fibrosis evolved and progressed between weeks 12
      and 17. Collagen alpha(1)(1) gene expression was upregulated by week 5 and
      increased fivefold by week 17. Stellate cells were the unique source of collagen
      gene expression. TIMP-1 and -2 were increased at week 12. Livers of MCD diet-fed
      rats exhibited lowered levels of GSH and elevated TBARS. Hepatocytes were the
      source of lipid peroxidation, and mRNA levels for TGFbeta1 were increased only in
      this cell type. CONCLUSIONS: The MCD model of 'fibrosing steatohepatitis'
      replicates the histologic features of human steatohepatitis, and the sequence of
      steatosis, inflammatory cell injury and fibrogenesis. The temporal sequence is
      consistent with a concept for involvement of oxidative injury in inflammatory
      recruitment and pathogenesis of hepatic fibrogenesis.

PMID- 14568260
TI  - Caspase-dependent apoptosis in fulminant hepatic failure induced by herpes
      simplex virus in mice.
AB  - BACKGROUND/AIMS: Herpes simplex virus (HSV) is known to induce fulminant hepatic
      failure. The aim of this study is to clarify the molecular basis of liver injury
      in HSV-induced hepatitis. METHODS: Immunocompetent mice were inoculated with HSV
      or ultraviolet-inactivated HSV (UV-HSV) intravenously. Extent of liver injury was
      evaluated by changes of serum enzymes and histopathology. Apoptosis was assessed
      by DNA fragmentation and terminal deoxynucleotidyl transferase-mediated dUTP nick
      end labeling (TUNEL). Immunohistochemistry for caspase-3 and Fas ligand was
      performed. Reverse transcriptase-polymerase chain reaction for Fas ligand was
      also performed. RESULTS: All mice died of rapid and massive liver cell death
      after HSV infection, whereas no change was observed in mice after UV-HSV
      inoculation. The extent of viral replication and DNA fragmentation correlated
      well with the severity of liver injury. Caspase-3 was activated in the liver
      after HSV infection, but not UV-HSV. Positive reaction for TUNEL was observed not
      only in HSV-antigen positive cells but also in HSV-antigen negative cells. Fas
      ligand was induced in the liver infected with HSV, but not with UV-HSV.
      CONCLUSIONS: Caspase-dependent apoptosis is involved in HSV-associated liver
      injury. Not only viral replication but also non-viral factor such as Fas ligand
      may facilitate rapid development of this disease.

PMID- 14568259
TI  - Mangafodipir prevents liver injury induced by acetaminophen in the mouse.
AB  - BACKGROUND/AIMS: Acute liver failure (ALF), characterized by massive hepatocyte
      necrosis, is often caused by drug poisoning, particularly with acetaminophen
      (APAP). Hepatocyte necrosis is consecutive to glutathione depletion by NAPQI, a
      metabolite of APAP, and to mitochondrial damages caused by reactive oxygen
      species (ROS) overproduction. Considering the structure of Mangafodipir, a
      contrast agent currently used in magnetic resonance imaging of the liver, we
      hypothesized that this molecule could exert an antioxidant activity and be
      possibly used as a treatment of APAP-induced ALF. METHODS/RESULTS: Mangafodipir
      is endowed with superoxide dismutase, catalase, and glutathione reductase
      activities. It can inhibit ROS production by hepatocytes in culture, and protect
      those cells from oxidative stresses induced by exposure to xanthine oxidase,
      H(2)O(2), or UV light. Moreover, preventive or curative administration of
      Mangafodipir to mice with APAP-induced ALF significantly increases survival
      rates, and abrogates aspartate aminotransferase elevation and histological
      damage. CONCLUSIONS: Those data point out the potential interest of Mangafodipir
      in the treatment of toxic ALF in humans.

PMID- 14568261
TI  - Osteoactivin expressed during cirrhosis development in rats fed a choline
      deficient, L-amino acid-defined diet, accelerates motility of hepatoma cells.
AB  - BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is closely associated with
      chronic liver diseases, particularly cirrhosis. However, the genes involved in
      hepatocarcinogenesis in the context of developing cirrhosis remain unknown. This
      study aims to identify genes associated with early cirrhosis-associated
      hepatocarcinogenesis. METHODS: We examined genes differentially expressed between
      the livers of normal rats and rats fed a choline-deficient, L-amino acid-defined
      (CDAA) diet using suppression subtractive hybridization. We examined both the
      expression in the liver and HCC tissues of osteoactivin (OA), isolated in this
      screen, and its effect on invasiveness and metastasis. RESULTS: OA mRNA was
      strongly expressed in the livers of rats fed the CDAA diet for 1-3 months.
      Moderate expression was sustained for 18 months. OA overexpression increased the
      invasiveness and metastasis of rat hepatoma cells in vitro and in vivo. In
      humans, OA expression was not detectable in normal liver tissues. While OA
      transcripts were detectable in cirrhotic nontumorous liver tissues surrounding
      HCCs, the majority of HCC tissue samples exhibited higher levels of OA expression
      than the surrounding normal tissue. CONCLUSIONS: These results indicate that OA
      is a novel factor involved in the progression of HCC via stimulation of tumor
      invasiveness and metastatic potential.

PMID- 14568262
TI  - Telomere shortening and telomerase reactivation in dysplastic nodules of human
      hepatocarcinogenesis.
AB  - BACKGROUNDS/AIMS: The maintenance of telomere with telomerase reactivation, vital
      for carcinogenesis, was studied in human multistep hepatocarcinogenesis for the
      characterization of borderline lesions. METHODS: The terminal restriction
      fragment length (TRFL) and telomerase activity (TA) were examined in 3 chronic
      hepatitis (CH), 10 cirrhosis, 7 large regenerative nodules (LRNs), 30 low grade
      dysplastic nodules (LGDNs), 6 high grade DNs (HGDNs), 3 DNs with hepatocellular
      carcinoma (HCC) foci, 11 HCCs, and 4 normal livers by Southern hybridization and
      TRAPeze Elisa telomerase detection. RESULTS: The TRFL and TA showed significant
      differences between the LGDNs and HGDNs. Most LGDNs had similar levels of TRFL
      and TA to those of the CH, cirrhosis and LRNs, however, 17% of LGDNs revealed
      shortening of telomeres up to the levels of HGDNs and 7% of LGDNs showed high
      levels of TA. The levels of TRFL and TA in HGDNs showed no significant
      differences from those of DNs with HCC foci and HCCs. CONCLUSIONS: The shortening
      of telomeres and reactivation of telomerase occur in the DNs during the early
      stages of hepatocarcinogenesis, with a significant change in the transition of
      LGDNs to HGDNs. The characteristics of HGDNs are considered to be closer to those
      of HCCs.

PMID- 14568263
TI  - Agmatine inhibits the proliferation of rat hepatoma cells by modulation of
      polyamine metabolism.
AB  - BACKGROUND/AIMS: Previous experiments have shown that agmatine, the product of
      arginine decarboxylase, is transported in competition with putrescine into
      quiescent rat hepatocytes, where it promotes several effects, including marked
      decrease of intracellular polyamines and induction of apoptosis. The primary aim
      of the present study was to assess the action of agmatine on transformed and
      proliferating hepatic rat cells. METHODS: To assess the effect of agmatine on
      hepatoma cells, analysis by flow cytometry, Western blotting, reverse
      transcription-polymerase chain reaction, scanning and transmission electron
      microscopy, immunofluorescence detection of beta-actin and alpha-tubulin were
      performed. RESULTS: The results showed that agmatine has antiproliferative
      effects on the cell lines studied (HTC, JM2, HepG2). Further experiments were
      performed on HTC cells. The effect was proportional to agmatine concentration (in
      a range between 50 and 500 microM). It was not correlated with induction of
      necrosis or apoptosis and was accompanied by accumulation in G(2)/M cell cycle
      phase and by dramatic modification of cell morphology. Spermidine reversed these
      effects, suggesting that the marked decrease of the polyamine pool is the main
      target of agmatine . CONCLUSIONS: The results obtained show a relationship
      between the decrease of intracellular polyamine content, the rate of cell growth
      and the cytoskeleton organization.

PMID- 14568264
TI  - Cytochrome P450 2A6: a new hepatic autoantigen in patients with chronic hepatitis
      C virus infection.
AB  - BACKGROUND/AIMS: Cytochromes P4502A6 (CYP2A6) and P4501A2 (CYP1A2) were described
      as hepatic autoantigens in the autoimmune polyglandular syndrome type-1 (APS-1).
      We evaluated the significance of anti-CYP2A6 and anti-CYP1A2 in several hepatic
      diseases in the absence of APS-1. METHODS: A radioligand assay (RLA) based on
      immunoprecipitation of [(35)S]-methionine-labeled CYP2A6 and CYP1A2 was used.
      Four hundred and thirty subjects with chronic viral hepatitis (n=185), autoimmune
      liver diseases (n=181), autoimmune rheumatic diseases (ARD, n=31) and healthy
      (n=33) were tested. RESULTS: Seven out of 366 patients with liver diseases were
      anti-CYP2A6 positive. Neither healthy nor ARD patients showed anti-CYP2A6. One
      out of 181 patients with autoimmune liver diseases tested anti-CYP2A6 positive. A
      significantly higher prevalence of anti-CYP2A6 (P<0.05) was detected with six out
      of seven patients positive in the viral hepatitis group. The latter were infected
      by flaviviruses (1 HGV/GBVC, 5 HCV). 4/5 HCV/anti-CYP2A6 positive sera were
      positive for anti-LKM-1 by immunofluorescence and for anti-CYP2D6 by RLA. None of
      the 430 sera recognized CYP1A2. CONCLUSIONS: For the first time CYP2A6 is
      reported as a hepatic autoantigen in patients with viral hepatitis caused by
      flaviviruses and in particular in HCV/anti-LKM-1 positive patients. Multicenter
      studies are needed in order to investigate the clinical importance of this novel
      finding. This study further supports that anti-CYP2A6 in the absence of
      flavivirus is rather limited to APS-1.

PMID- 14568265
TI  - Lymph node enlargement within the hepatoduodenal ligament in patients with
      chronic hepatitis C reflects the immunological cellular response of the host.
AB  - BACKGROUND/AIMS: Lymph nodes in the hepatoduodenal ligament seem to be a common
      ultrasonographic finding in patients with chronic hepatitis C. Lymphadenopathic
      enlargement is associated with the histological hepatic features reflecting the
      immunological response of the host, but the correlation between lymphadenopathy,
      liver histology and the cellular immunoreactivity of the host has never been
      studied. AIM: (1) To specify the prevalence of lymph nodes within the
      hepatoduodenal ligament; and (2) to investigate whether lymphadenopathies might
      reflect the immunological response of the host. METHODS: One hundred and eleven
      patients were enrolled in this study. Eleven chronic hepatitis B patients and 34
      healthy volunteers served as controls. RESULTS: Lymph nodes were detectable in 90
      out of the 104 chronic hepatitis C patients studied. After logistic regression, a
      high CD8 level and the absence of post hepatitis C cirrhosis were associated with
      lymph node enlargement. The total lymph node volume was correlated with
      transaminase levels, inflammatory activity, and stage of fibrosis. CONCLUSIONS:
      (1) The prevalence of lymph nodes within the hepatoduodenal ligament is high; (2)
      lymph node enlargement is correlated with the immunological cellular response of
      the host; and (3) the total lymph node volume is correlated with hepatic
      necroinflammatory markers and the stage of fibrosis.

PMID- 14568266
TI  - Screening for hepatitis C in genito-urinary medicine clinics: a cost utility
      analysis.
AB  - BACKGROUND/AIMS: To estimate the cost utility (cost per QALY) of screening for
      hepatitis C (HCV) infection in people attending genito-urinary medicine clinics
      in England. METHODS: An epidemiological model of screening and diagnosis was
      combined with a Markov chain model of treatment with combination therapy to
      estimate cost utility. Parameters for the model were informed by literature
      review, expert opinion and a survey of current screening practice. RESULTS: The
      base case estimate was about pound 85,000 per QALY. Selective screening is more
      cost effective. If screening is restricted to only 20% or 10% of attenders, cost
      utility is estimated as pound 39,647 and pound 34,288 per QALY. If screening is
      restricted only to those with a history of injecting drug use, cost utility would
      be pound 27,138 per QALY. Estimates are particularly sensitive to acceptance
      rates for screening and treatment. CONCLUSIONS: Universal screening for HCV in
      GUM clinics is unlikely to be cost effective. There is limited evidence to
      support screening of people other than those with a history of injecting drug use
      and even this policy should be considered with some care and in the context of
      further research.

PMID- 14568267
TI  - Antiviral effect of ribavirin in early non-responders to interferon monotherapy
      assessed by kinetics of hepatitis C virus RNA and hepatitis C virus core antigen.
AB  - BACKGROUND/AIMS: To evaluate the efficacy of ribavirin, given in second intention
      in non-responders to interferon alone, by studying viral kinetics. METHODS: We
      conducted a trial including 203 patients with chronic hepatitis C, naive of
      treatment. Patients were treated with interferon three times a week with or
      without ribavirin and amantadine according to response. Viral kinetics were
      assessed by serial measurements of HCV RNA (bDNA 3.0 and Monitor 2.0) and a new
      assay, trak-C, able to quantify total Hepatitis C virus (HCV) core antigen.
      RESULTS: A significant initial drop in HCV RNA or HCV core antigen, under
      interferon alone, was associated with response to therapy, -4.85+/-1.33 log for
      HCV RNA in sustained responders versus -1.86+/-1.53 log for others groups,
      P<0.001. In patients receiving ribavirin in second intention, we also observed a
      similar drop in HCV RNA and HCV core antigen, predictive of sustained response, 
      2.67+/-1.26 log for HCV RNA in sustained responders versus -0.44+/-0.49 log in
      non-responders, P<0.001. CONCLUSIONS: Ribavirin has probably an additional
      antiviral effect in interferon treated patients. Kinetics of HCV RNA and HCV core
      antigen under treatment are highly predictive of a sustained virological
      response.

PMID- 14568268
TI  - The role of inducible nitric oxide synthase in a murine acute hepatitis B virus
      (HBV) infection model induced by hydrodynamics-based in vivo transfection of HBV
      DNA.
AB  - BACKGROUND/AIMS: Inducible nitric oxide synthase (iNOS) is found to have
      antiviral activity. Its role is evaluated using a murine acute hepatitis B virus
      (HBV) infection model. METHODS: pHBV3.6 plasmid containing HBV genome was
      injected into mice by hydrodynamics-based in vivo transfection. HBV antigenemia
      and serum HBV-DNA were detected by enzyme-linked immunosorbent assay (ELISA) and
      polymerase chain reaction, respectively. HBV replication in liver was analyzed by
      Northern and Southern blot. Intrahepatic leukocytes were isolated and analyzed
      with flow cytometry. RESULTS: After hydrodynamics injection of pHBV3.6, HBV
      genome was synthesized in the liver and HBV-DNA, as well as hepatitis B surface
      antigen and hepatitis B e antigen were secreted into the blood. Anti-HBV antibody
      responses developed afterward. A murine acute HBV infection model was established
      with hydrodynamics injection of non-transponase based HBV-DNA. Using this
      protocol in iNOS deficient or wild type B6 mice, the level of HBV transcript,
      replicative intermediate, and antigenemia were higher in iNOS(-/-) than in B6
      mice. The intrahepatic leukocytes in iNOS(-/-) mice were also affected after
      transfection. CONCLUSIONS: Our data suggests that the iNOS expression not only
      affects the HBV clearance, but also modulates the infiltrating leukocytes
      response to HBV antigens.

PMID- 14568269
TI  - A randomized trial of consensus interferon in combination with ribavirin as
      initial treatment for chronic hepatitis C.
AB  - BACKGROUND/AIMS: The aim of the present, open-labeled, randomized study was to
      determine the efficacy and safety of different doses of consensus interferon plus
      ribavirin in the initial treatment of chronic hepatitis C. METHODS: One hundred
      and one genotype 2/3 patients were randomized to receive 9 mcg (group A, n=48) or
      18 mcg (group B, n=53) of consensus interferon thrice weekly plus ribavirin
      (1000/1200 mg/daily) for 24 weeks and 92 genotype 1 patients to receive 9 mcg
      (group C, n=47) or 18 mcg (group D, n=45) of consensus interferon plus ribavirin
      for 48 weeks. RESULTS: In an intention-to-treat analysis, the sustained virologic
      response at 24-week follow-up was 69% and 66% for group A and B (P=0.77) and 40%
      and 36% for group C and D (P=0.63). The overall sustained response was 67% and
      38% in patients with genotype 2/3 and 1, respectively. Among genotype 1 patients
      the sustained virologic response was 39% and 41% for high or low baseline viremia
      levels. CONCLUSIONS: Higher consensus interferon dose does not increase sustained
      virologic response. Naive genotype 1 patients may achieve significant response
      rate of approximately 40% if treated with 9 mcg of consensus interferon plus
      ribavirin for 48 weeks.

PMID- 14568270
TI  - Clinical outcome and virologic profiles of severe hepatitis B exacerbation due to
      YMDD mutations.
AB  - BACKGROUND/AIMS: To study the outcome and the virologic profiles of severe
      hepatitis exacerbations due to YMDD mutants in lamivudine-treated patients.
      METHODS: Eighteen lamivudine-treated patients with severe hepatitis exacerbations
      due to YMDD mutants were recruited. Laboratory and clinical parameters were
      monitored. Viral genotypes and YMDD mutations were determined. RESULTS: None of
      the 18 patients had YMDD wild-type during exacerbations. Three (17%) and 15 (83%)
      patients had genotypes B and C, respectively. Elevated bilirubin levels and
      prolonged prothrombin time were found in 11 (61%) and six patients (33%)
      respectively. Three patients (17%) had adverse outcome with the development of
      ascites and/or encephalopathy. One of these patients required liver
      transplantation and one died. Both patients had evidence of cirrhosis before
      treatment and hepatitis B e antigen (HBeAg) seroreversion from anti-HBe
      positivity. The remaining 16 patients (89%) have no evidence of pre-existing
      cirrhosis. Thirty seven percent of patients had normal alanine aminotransferase
      levels at the last follow-up. The median HBV DNA level at the last follow-up was
      significantly lower than the pre-treatment level (P=0.009). CONCLUSIONS: Though
      the majority of patients with severe hepatitis exacerbations due to YMDD mutants
      had uneventful course, early liver transplantation should be considered in
      patients with pre-existing cirrhosis and HBeAg seroreversion.

PMID- 14568271
TI  - The tightrope of therapeutic suppression of active transforming growth factor
      beta: high enough to fall deeply?

PMID- 14568272
TI  - Cytochrome P450 2A6 meets P450 2D6: an enigma of viral infections and
      autoimmunity.

PMID- 14568273
TI  - Water handling and aquaporins in bile formation: recent advances and research
      trends.

PMID- 14568275
TI  - Endoscopic removal of choledocholithiasis over a migrating silk thread in a
      patient with previous cholecystectomy.

PMID- 14568274
TI  - Successful treatment of hepatitis C after kidney transplantation with combined
      interferon alpha-2b and ribavirin.
AB  - The management of acute hepatitis C virus (HCV) infection after renal
      transplantation (RT) remains controversial, due to the potential risk of
      interferon-induced graft dysfunction. There is little experience with combined
      interferon and ribavirin therapy in this group of patients. We treated four
      consenting RT recipients who developed acute de novo HCV infection with a
      combination of interferon-alpha 2b and ribavirin. After 48 weeks' treatment,
      sustained virologic and biochemical remission were achieved in three patients
      infected with HCV genotypes 1a, 2, and 6a, respectively. The median time from
      treatment onset to ALT normalization was 8 weeks. The fourth patient was a non
      responder infected with genotype 1b. Dose-dependent hemolysis was the most
      frequent side-effect. No patient developed allograft dysfunction. Our experience
      indicates that the judicious use of combined interferon and ribavirin can be
      considered in selected RT recipients with severe acute hepatitis C infection.

PMID- 14568276
TI  - Lamivudine 'as needed': a novel therapeutic approach for HBe-minus chronic
      hepatitis.

PMID- 14568277
TI  - The association of elevated serum bilirubin levels and coronary heart disease.

PMID- 14568278
TI  - Targeted use of siRNA in animal models of hepatic damage: an innovative therapy
      for acute liver failure.

PMID- 14568281
TI  - HT and breast cancer risk.
AB  - Two large recent studies indicate an increased risk of breast cancer with use of
      menopausal hormone therapy (HT), particularly combinations of estrogen and
      progestogen. These studies also go against previous theories of the types of
      breast cancer that would be associated with HT use. Emerging information
      regarding the influence of estrogen plus progestin on breast cancer risk adds
      further weight to the recommendation against use for chronic disease risk
      reduction and raises additional questions regarding risks of even short-term use
      for vasomotor symptoms associated with menopause.

PMID- 14568282
TI  - HT and CVD prevention. from myth to reality.
AB  - Menopausal hormone therapy has no evidence-based role for the primary or
      secondary prevention of coronary heart disease. Coronary prevention should
      involve lifestyle and pharmacologic interventions documented as beneficial in
      randomized clinical trials and promulgated in national guidelines.

PMID- 14568283
TI  - HT. A clinician demurs.
AB  - The ongoing challenge to clinicians is to make medical judgments that are
      suitable for patients as individuals with unique combinations of medical needs.
      The cancellation of the WHI study's estrogen/progestin arm leaves unanswered
      questions that will affect clinicians' medical decisions.

PMID- 14568284
TI  - How does the WHI study alter the risk-benefit ratio of HT?
AB  - Good clinical practice depends on knowledge of the current best medical care
      research evidence, but clinicians must be able to determine what is the best
      evidence and whether this evidence is relevant to their own patients. At the
      heart of evidence-based medicine is the assessment of the validity, importance,
      and relevance of a given study. These may be evaluated by asking key questions;
      here these questions are applied to the WHI study.

PMID- 14568285
TI  - Just the facts, ma'am. Coming clean about fertility.
AB  - In an American Infertility Association survey of more than 12,000 women, only one
      respondent answered all 15 questions about the reproductive lifecycle and basic
      fertility correctly. What women now need from their OB-GYNs is open discourse
      about fertility, its preservation, and its natural, inevitable decline.
      Discussion about lifestyle choices that may affect fertility should take place
      before a patient begins family-building, as insights into how the body functions
      may empower women to make sounder lifestyle judgments.

PMID- 14568286
TI  - Avoiding complications of laparoscopic surgery.
AB  - No matter how skilled the surgeon, the risk of complications always exists.
      Complications of laparoscopic surgery include anesthesia difficulties,
      positioning and nerve injuries, injuries due to insertion of needles and trocars,
      and intraoperative vascular, bowel, and urinary tract injuries. Injuries from
      electrosurgical equipment may also result. This article focuses on preventing
      such complications.

PMID- 14568287
TI  - New treatments for erectile dysfunction.
AB  - Erectile dysfunction (ED) is an increasingly common problem, affecting up to 30
      million American men. This largely results from increased risk factors and an
      aging population. ED is now also recognized as a marker for cardiovascular
      disease. The ED patient should be thoroughly evaluated for coexisting vascular
      disease. The pathophysiology of ED is becoming better understood, largely as a
      result of the development of new therapies. Once the underlying processes are
      known, more selective targeting of these will lead to novel "designer drugs."

PMID- 14568288
TI  - Yoga: an adjunct to infertility treatment.
AB  - Yoga and meditation can help women experiencing the challenges of infertility.
      The practice of meditation and relaxation can help increase the clarity of the
      mind, maintain healthy body chemistry, and give patients the patience to undergo
      the rigors of infertility treatments. When one understands and can attain
      physical relaxation, one tends to feel better about the body itself, and begins
      to treat the body with more respect. This understanding can lead to healthier
      lifestyle habits as well as increased sensitivity regarding symptoms and body
      processes. This is beneficial to both doctor and patient as the patient can
      report with more clarity and sense cycles and physical issues more readily.

PMID- 14568289
TI  - Assessment of individual sensitivity to ionizing radiation and DNA repair
      efficiency in a healthy population.
AB  - Inter-individual variation in response to exposure to carcinogens has been
      ascribed to differences in carcinogen metabolism as well as to variability in DNA
      repair capacity (DRC). In order to investigate the role of inherited and acquired
      factors on individual variation in DNA repair capacity, a mutagen sensitivity
      assay was carried out on 31 healthy subjects. Fresh blood samples were irradiated
      with gamma-rays (2Gy) and the kinetics of DNA repair in leukocytes assessed by
      the comet assay 0, 15, and 30 min after irradiation. Whole blood cultures were
      set up to detect spontaneous and induced structural chromosomal aberrations in
      lymphocytes 48 h after irradiation. The results obtained were evaluated with
      respect to age, gender, smoking habits, occupational exposure to chemicals and
      metabolic genotype (NQO1, GSTM1 and GSTT1) of the study subjects. A higher
      frequency of radiation-induced aberrations was observed in GSTM1-positive
      individuals compared with GSTM1-null subjects (P=0.025), as well as in non
      smokers compared with heavy smokers (P=0.05). Similar results were obtained by
      measuring residual DNA damage (RD) shortly after irradiation by means of the
      comet assay, with non-smokers showing a higher amount of RD compared with smokers
      (P=0.016). Moreover, a significant correlation (P=0.008) was observed between the
      amount of RD and the frequency of chromosome breaks after irradiation. The
      results of this pilot study suggest a modulator effect of smoking habits and
      GSTM1 genotype on the individual DNA repair capacity, possibly related to the
      higher expression of enzymes involved in the repair of oxidative DNA damage in
      heavy smokers and GSTM1-null subjects.

PMID- 14568290
TI  - Enhanced prediction of potential rodent carcinogenicity by utilizing comet assay
      and apoptotic assay in combination.
AB  - The comet assay has been recently validated as a sensitive and specific test
      system for the quantification of DNA damage. The objectives of this study are to
      investigate the utility of comet assay for detecting mutagens with 11 substances
      that demonstrated positive results in at least one test among four standard short
      term genotoxicity tests, and to evaluate its ability to predict rodent
      carcinogenicity. Out of 11 test substances, positive comet results were obtained
      for colchicine, hydroxyurea and actinomycin D. No effect on DNA migration,
      determined as the tail moment, was found with theophylline or 2,4-dinitrophenol.
      Bisphenol A, vinblastine, paclitaxel and p-anisidine appeared cytotoxic
      clastogens because these induced tail moment at concentrations showing 60% or
      less cell survival. In addition, among three test substances showing the bimodal
      distribution of DNA damage, which is a characteristic of apoptosis, true
      apoptosis result was obtained for camptothecin and dexamethasone with the Annexin
      V affinity assay. With this limited data-set, an investigation into the
      predictive value of these short-term genotoxicity tests for determining the
      carcinogenicity showed that comet assay has relatively high sensitivity and
      superior specificity to other four short-term genotoxicity assay. Therefore, our
      data suggest that comet assay, especially in combination with apoptotic assay,
      would be a good predictive test to minimize false-positives in evaluation of the
      potential rodent carcinogenicity.

PMID- 14568291
TI  - The Salmonella mutagenicity of industrial, surface and ground water samples of
      Aligarh region of India.
AB  - The genotoxicity of three water bodies, viz. industrial waste water of Aligarh
      city, ground water pumped out from the industrial area of Aligarh, and river
      water of Yamuna, downstream of Agra, was carried out by means of Ames plate
      incorporation test and the Ames fluctuation test. All the test samples were
      significantly mutagenic in both the testing systems. The ground water and river
      water samples were subjected to XAD concentration prior to the
      mutagenicity/genotoxicity testing, while the industrial waste water was used
      directly. Whereas TA98, TA102 and TA104 strains have been found to be maximally
      sensitive in the Ames plate incorporation assay conducted for various water
      samples, TA98 and TA100 strains were the most responsive strains in the Ames
      fluctuation test. The apparent disparity in the sensitivity patterns of various
      Ames strains by plate incorporation and fluctuation assays could be attributed to
      a large extent to the different conventional ways of interpretation of the data
      in these systems.

PMID- 14568292
TI  - Comparison of DNA damage detected by plant comet assay in roadside and non
      roadside environments.
AB  - Although mixed air pollutants generated from traffic are suspected as one of the
      causes of DNA damage in living species, effects of the combination of these
      pollutants and other micro-environmental factors on urban biota have not been
      clarified yet. Thus, this study mainly aimed to detect the genetic damages in
      selected plant biomonitors, which were ginkgo (Ginkgo biloba), pohtos (Epipremnum
      aureum), and periwinkle (Vinca rosea), setting in roadside and non-roadside
      environments. Two monitoring positions were selected in the Hongo campus of the
      University of Tokyo, Japan. This area was categorized as the urban residential
      zone. Both roadside and non-roadside samples were analyzed by using comet assay
      protocol. Different distribution changes in DNA migration ratios of all species
      could be observed and further interpreted as percentages of DNA damage. For all
      test species, in the final stage of experiment, roadside samples showed
      significantly higher degrees of DNA damage than non-roadside one. Time-dependent
      response pattern of each species to the overall environmental stresses was
      performed. Increase in the percentages of DNA damage could be expressed by
      regression equations. In addition, ratio of percentage of DNA damage between
      roadside and non-roadside species (R/N ratio) was introduced in order to clarify
      the additional genetic effect caused by roadside air pollutants. Series of
      response phase of plant under stresses, including cell destabilization, damage
      intensification, and re-stabilization, were explained. This study might be
      applied as a preliminary method in urban air quality assessment for detecting the
      existing effects of air pollutants and micro-environmental stress in an urban
      ecosystem.

PMID- 14568293
TI  - Beta-glucan inhibits the genotoxicity of cyclophosphamide, adriamycin and
      cisplatin.
AB  - The inhibitory effects of beta-glucan (betaG), one of the biological response
      modifiers, on the induction of chromosomal aberrations in the bone marrow and
      spermatogonial cells of mice treated with various anti-neoplastic drugs were
      investigated. beta-Glucan (100 mg/kg bw, i.p.) pre-treatment reduced the total
      number of cells with structural chromosomal aberrations scored after the
      treatment with cyclophosphamide (CP) (2.5 mg/kg bw, i.p.) adriamycin (ADR) (12
      mg/kg bw, i.p.) and cis-diamminedichloroplatinum-II (cisplatin) (5 mg/kg bw,
      i.p.) by about 41.1, 26.9 and 57.7% in bone marrow and 44.4, 55 and 57.1% in
      spermatogonial cells, respectively. This protective effect of beta-glucan could
      be attributed to its scavenging ability to trap free-radicals produced during the
      biotransformation of these anti-neoplastic drugs. Beta-glucan also markedly
      restored the mitotic activity of bone marrow cells that had been suppressed by
      the anti-neoplastic drugs. These results indicate that in addition to the known
      immunopotentiating activity of beta-glucan, it plays a role in reducing
      genotoxicity induced by anti-neoplastic drugs during cancer chemotherapy.

PMID- 14568294
TI  - Genotoxic effects of volatile organic compounds in a chemical factory as
      evaluated by the Tradescantia micronucleus assay and by chemical analysis.
AB  - The clastogenic effects of volatile organic compounds in the workplace air of a
      chemical factory were studied by means of the Tradescantia micronucleus (Trad
      MCN) assay and chemical analysis. Sampling was performed at a chemical factory
      producing PVC film in Cheong-ju, South Korea. Inflorescences of Tradescantia BNL
      4430 were placed for 2, 6, and 9 h at the height of 1.40 m at two locations in
      the workplace and one outdoor of the chemical industry. Air samplings were
      conducted in the same places and the collected tube samples were analyzed by
      automatic thermal desorption/gas chromatography/mass spectrometry (ATD/GC/MS).
      The frequencies of micronuclei in specimens exposed for 2 h in sites 1-3 were
      6.13 +/- 0.47, 5.40 +/- 1.60, and 2.93 +/- 0.43 MCN per 100 tetrads,
      respectively. GC/MS analysis proved the presence of various volatile organic
      compounds such as trichloroethylene, toluene, ethyl benzene, (m, p, o)-xylene,
      styrene, 1,3,5-trimethyl benzene, and 1,2,4-trimethyl benzene. Mean values of
      toluene measured by 2 h sampling in sites 1-3 were 1946.6, 1368.3, and 340.1
      microg/m3, respectively. The toluene concentrations in sites 1 and 2 were at
      least four to six times higher than that in site 3. The micronucleus frequencies
      increased with exposure time. In addition, there was a correlation between the
      micronucleus frequencies and toluene concentration in the air (R2 = 0.96). The
      results of this in situ monitoring proved the applicability of the Trad-MCN assay
      combined with chemical analysis for monitoring genotoxic chemicals in the work
      environment.

PMID- 14568295
TI  - DNA damage in zebrafish larvae induced by exposure to low-dose rate gamma
      radiation: detection by the alkaline comet assay.
AB  - This study has determined the sensitivity of the alkaline comet assay for the
      detection of strand breaks in the DNA of cells taken from a whole organism rather
      than a single cell type as in previously reported studies. The assay has been
      performed on cells from whole zebrafish larvae irradiated for 1 or 24 h at dose
      rates of 0.4, 1.2 or 7.2 mGy/h. Zebrafish larvae exposed to only 1.2 mGy/h of
      gamma-radiation for 1h showed a statistically significant increase in DNA damage
      compared to controls. This represents a high sensitivity of this animal model for
      DNA damage and of the comet assay protocol used for detecting such damage.
      Increasing the exposure time from 1 to 24 h caused significant increases in DNA
      damage in zebrafish larvae, although the modest size of these increases in damage
      for the relatively large increases (24 times) in total absorbed dose indicates
      that dose rate may be the major factor in determining the level of DNA damage
      observed under the conditions of these experiments.

PMID- 14568296
TI  - Effects of ALDH2 gene polymorphisms and alcohol-drinking behavior on micronuclei
      frequency in non-smokers.
AB  - Alcohol abuse is a serious health problem, leading to life-threatening damage to
      most of the important organ systems. Genotoxic damage is used as an early effect
      indicator in the surveillance of human exposure to genotoxic substances. Intra-
      and inter-individual variations of baseline frequencies of micronuclei (MN) in
      peripheral blood lymphocytes of human populations have been reported previously.
      Polymorphisms in a few metabolic enzyme genes seem to account for a proportion of
      this variability, but the impact of specific genetic variants on MN frequencies
      has not yet been clarified. In 42 healthy Japanese non-smoking men, we
      investigated the relationship between the MN frequency levels and genetic
      polymorphisms in three different genes: aldehyde dehydrogenase 2 (ALDH2), X-ray
      repair cross-complementing group 1 (XRCC1) and excision repair cross
      complementing group 2 (ERCC2). Genotyping was performed by PCR-RFLP analysis. The
      ALDH2 variant (deficient-type) was significantly associated with increased MN
      frequency levels in subjects with drinking more than three times per week,
      whereas the XRCC1 and ERCC2 variants seemed to be unrelated to the MN frequency.
      The ALDH2-deficient habitual drinkers had an average MN frequency of 5.88+/-0.58
      (+/- S.E.) compared with 3.20 +/- 0.80 in the ALDH2-proficient habitual drinkers
      (P<0.05). The ALDH2-proficient non-habitual drinkers had the lowest MN frequency
      (1.56 +/- 0.41). Furthermore, subjects with highest levels of mean MN frequency,
      who consumed more than 100g of alcohol per week and more than three times per
      week, had A2 genotype of ALDH2. A significant odds ratio (12.25, P<0.05) for the
      MN frequency levels above the 50th percentile value was observed for the ALDH2
      deficient individuals versus the ALDH2-proficient individuals after adjustment
      for several confounders. These results strongly suggest that human early
      genotoxic effect studies based on the cytogenetic markers of MN should take into
      account both the individual ALDH2 polymorphism and the potential confounding
      effect of the drinking behavior.

PMID- 14568297
TI  - Effects of high frequency electromagnetic fields on micronucleus formation in CHO
      K1 cells.
AB  - To investigate the effects of high frequency electromagnetic fields (HFEMFs), we
      assessed the frequency of micronucleus (MN) formation induced by chromosomal
      breakage or inhibition of spindles during cell division in Chinese hamster ovary
      (CHO)-K1 cells, using the cytokinesis block micronucleus method. The MN frequency
      in cells in the inner, middle and outer wells of an annular culture plate was
      determined for the following four conditions: (1) CHO-K1 cells were exposed to a
      HFEMF for 18 h at average specific absorption rates (SARs) of 13, 39 and 50 W/kg
      with input power 7.8 W, and were compared with a sham-exposed control; (2) the
      cells were also exposed to a HFEMF at SARs of 78 and 100 W/kg with input power 13
      W, and were compared with a sham-exposed control; (3) the cells were treated with
      bleomycin alone or with bleomycin followed by exposure to a HFEMF for 18 h at
      SARs of 25, 78 and 100 W/kg, and were compared with a bleomycin-treated positive
      control. The cells treated with bleomycin alone were compared with sham-exposed
      controls; and (4) As a high temperature control, CHO-K1 cells were incubated at
      39 degrees C for 18 h. In study (1), the MN frequency of cells exposed to a HFEMF
      at a SAR of up to 50 W/kg was not different to that in sham-exposed cells. In
      study (2), there were statistically significant increases in the MN frequencies
      of cells in the middle and outer wells of the annular culture plate caused by
      exposure to a HFEMF at 100 and 78 W/kg, respectively. In study (3), the MN
      frequencies of cells in the middle (100 W/kg) and outer wells (78 W/kg) of the
      annular culture plate were statistically higher than that caused by bleomycin
      treatment alone. In study (4), there was a statistically significant increase of
      MN frequency in the cells treated by heat at 39 degrees C. These results indicate
      that cells exposed to a HFEMF at a SAR of 78 W/kg and higher form MN more
      frequently than sham-exposed cells, while exposure to a HFEMF at up to 50 W/kg
      does not induce MN formation. In addition, a HFEMF at a SAR of 78 W/kg and higher
      may potentiate MN formation induced by bleomycin-treatment.

PMID- 14568298
TI  - Low dose genotoxicity of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) in
      gpt delta transgenic mice.
AB  - Although humans are chronically exposed to most environmental chemicals at low
      doses, genotoxicity assays with rodents are usually performed at high doses with
      short treatment period. To investigate the dose-response of genotoxicity at lower
      doses, gpt delta transgenic mice were fed a diet containing 300, 30 or 3 parts
      per million (ppm) of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) for 12
      weeks and the gpt mutations in the liver were analyzed. In addition, the mice
      were continuously fed a diet containing MeIQx at a dose of 300 ppm for 78 weeks
      to examine the effect of a long-term treatment. In the mice treated for 12 weeks,
      the gpt mutant frequencies (MFs) were 8.6-, 2.3- and 1.2-fold higher than the
      control level at the doses of 300, 30 and 3 ppm, respectively. G:C to T:A
      transversion was the most predominant type of mutations and the fold increases in
      the specific MF of G:C to T:A were 58.2, 4.4 and 1.7 above the control at the
      three doses, respectively. The increases in the whole gpt and specific MFs at 3
      ppm were not statistically significant. In the mice treated with 300 ppm of MeIQx
      for 78 weeks, the gpt MF was about 20 times higher than that of the untreated
      mice fed a control diet for 78 weeks, which was about two times higher than that
      of the untreated mice at 12 weeks. These results suggest that no obvious
      genotoxic effects can be detectable at the dose of MeIQx at 3 ppm in the liver
      and a longer treatment substantially enhances the genotoxicity. Factors
      constituting the practical threshold dose are discussed.

PMID- 14568299
TI  - Comparison of the mutagenic activity of XAD4 and blue rayon extracts of surface
      water and related drinking water samples.
AB  - The combination of mutagenicity tests and selective extraction methodologies can
      be useful to indicate the possible classes of genotoxic organic contaminants in
      water samples. Treated and source water samples from two sites were analyzed: a
      river under the influence of an azo dye-processing plant discharge and a
      reservoir not directly impacted with industrial discharges, but contaminated with
      untreated domestic sewage. Organic extraction was performed in columns packed
      with XAD4 resin, that adsorbs a broad class of mutagenic compounds like
      polycyclic aromatic hydrocarbons (PAHs), arylamines, nitrocompounds, quinolines,
      antraquinones, etc., including the halogenated disinfection by-products; and with
      blue rayon that selectively adsorbs polycyclic planar structures. The organic
      extracts were tested for mutagenicity with the Salmonella assay using TA98 and
      TA100 strains and the potencies were compared. A protocol for cleaning the blue
      rayon fibers was developed and the efficiency of the reused fibers was analyzed
      with spiked samples. For the river water samples under the influence of the azo
      type dye-processing plant, the mutagenicity was much higher for both blue rayon
      and XAD4 extracts when compared to the water from the reservoir not directly
      impacted with industrial discharges. For the drinking water samples, although
      both sites showed mutagenic responses with XAD4, only samples from the site under
      the influence of the industrial discharge showed mutagenic activity with the blue
      rayon extraction, suggesting the presence of polycyclic compounds in those
      samples. As expected, negative results were found with the blue rayon extracts of
      the drinking water collected from the reservoir not contaminated with industrial
      discharges. In this case, it appears that using the blue rayon to extract
      drinking water samples and comparing the results with the XAD resin extracts we
      were able to distinguish the mutagenicity caused by industrial contaminants from
      the halogenated disinfection by-products generated during water treatment.

PMID- 14568300
TI  - Clastogenic effects of the fasciolicide drug fasinex on river buffalo lymphocyte
      cultures in vitro.
AB  - Fasinex (triclabendazole) has been reported to be an active fasciolocidal agent
      used in humans and in farm animals. The clastogenic effects of fasinex were
      tested in lymphocyte cultures of the river buffalo at three final concentrations:
      25, 50 and 100 microg/ml. Chromosomal aberrations, sister chromatid exchanges and
      micronucleus formation are the three cytogenetic parameters used in this study.
      The results demonstrated that the number of cells with different types of
      chromosomal aberrations, including chromatid breaks and gaps, isochromatid breaks
      and gaps and polyploidy, was increased significantly in cultures treated with
      different doses of fasinex compared to the control. This increase was dose
      dependent where there was a positive correlation between increased drug
      concentration and induction of chromosomal aberrations. The frequency of sister
      chromatid exchanges and the formation of micronuclei in all lymphocyte cultures
      treated with different doses of fasinex were increased significantly compared to
      the control; these increases were also dose-dependent. In conclusion, the three
      cytogenetic parameters used to evaluate the effect of fasinex revealed that the
      drug has a strong clastogenic effect on river buffalo lymphocytes in vitro.

PMID- 14568302
TI  - Effects of quinpirole on behavioral extinction.
AB  - Behavioral effects of quinpirole (QNP), a dopamine D(2) receptor agonist, suggest
      it impacts neural mechanisms mediating goal-directed behaviors, as well as
      behavioral extinction following removal of a primary reinforcer. The present
      study investigated the effect of QNP on behavioral extinction following the
      omission of contingent reinforcement, and whether this effect is related to
      acquisition or processes specific to extinction. Rats were trained on a
      continuous reinforcement schedule to nose-poke for water reward. Using a free
      operant procedure, rats completed approximately 70 responses for each of four
      consecutive days. On the fifth day reward was withheld. Rats were assigned to one
      of five groups in which they received 0.3 mg/kg QNP ip either during the first
      day (acquisition phase), the second 2 days (maintenance phase), the last day
      (extinction phase), or during all days. A fifth group received vehicle
      injections. Rats receiving QNP during the acquisition and maintenance phase did
      not differ significantly from the control group during the extinction phase,
      although they demonstrated reduced response rates on days they received QNP.
      However, rats treated during the extinction phase or during all phases
      demonstrated a significant reduction in the rate of extinction. This effect
      cannot be attributed to an increase in general behavioral arousal because
      response rates for reinforced responses did not differ significantly among groups
      following acquisition of the behavior. The reduced extinction effect does not
      appear to be related to abnormalities in the initial behavior-reward association,
      but instead may result from enhanced engagement of learned behavioral patterns,
      or from interference of signals associated with removal of predicted
      reinforcement.

PMID- 14568301
TI  - Possibility of the involvement of 9H-pyrido[3,4-b]indole (norharman) in
      carcinogenesis via inhibition of cytochrome P450-related activities and
      intercalation to DNA.
AB  - This study investigated the inhibitory effect of 9H-pyrido[3,4-b]indole
      (norharman), one of the naturally occurring beta-carbolines, on cytochrome P450
      (CYP)-related activities and the relationship between its inhibitory effect, its
      intercalation to DNA, and its comutagenic effect. Norharman reduced the
      mutagenicities of heterocyclic amines (HCAs) containing 2-amino-6
      methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1), aflatoxin B1, benzo[a]pyrene
      (BP), and some nitrosamines in the presence of 10 microl liver S9 (20.9 microg
      protein/ml) from polychlorinated biphenyl-treated rats. Norharman inhibited
      microsomal CYP-related enzyme activities and CO-binding to the CYP heme (50%
      inhibitory concentration (IC50), 0.07-6.4 microg/ml). It also inhibited the
      formation of 3-hydroxyamino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (N-OH-Glu-P
      1) and was a noncompetitive-inhibitor of CYP1A-related activities, while it
      enhanced the direct mutagenicity of N-OH-Glu-P-1 (50% effective concentration,
      25.0 microg/ml) and inhibited topo I activity (IC50, 31.0 microg/ml). In the
      presence of norharman, S9 up to 100 microl incrementally enhanced the
      mutagenicities of HCAs, BP and dimethylnitrosamine. These data clarified that
      norharman acts as an inhibitor of the CYP-mediated biotransformation of Glu-P-1
      via inhibition of O2-binding to CYP heme, and its inhibition of CYP enzymes
      occurs at much lower concentration than that for its intercalation to DNA. It is
      indicated that norharman's inhibitory effect on CYP results in the inhibition of
      excess metabolism by S9 and this is more likely the mechanism for comutagenic
      action than the intercalation. Norharman's inhibition of CYP and its enhancement
      of the N-OH-Glu-P-1 mutagenicity suggest that beta-carbolines modulate chemical
      carcinogenesis by controlling the xenobiotic metabolism and by intercalating to
      DNA.

PMID- 14568303
TI  - Effect of melatonin on total food intake and macronutrient choice in rats.
AB  - Melatonin, a hormone secreted in a rhythmic manner over 24 h mainly by the pineal
      gland, is used to alleviate the symptoms of jetlag and treat sleeping problems.
      The objective of the present study was to examine the effects of a 7-h phase
      shift from the natural peak of melatonin secretion on total food intake and
      macronutrient selection. Forty-eight adult Wistar rats of both sexes were divided
      in three dietary groups, each group offered a simultaneous and different choice
      of a carbohydrate- and a protein-rich diet. Macronutrient intakes following
      intraperitoneal administration of four doses of melatonin (3000, 6000, 10000 and
      15000 pg/ml blood) at dark onset were examined. Melatonin increased short- (4 h
      postinjection) and long-term (12 h postinjection) nocturnal total food intake in
      both male and female rats, mainly with the two highest doses. This effect of
      melatonin was mainly due to a short-term increase of intake across all
      carbohydrate-rich diet preparations (dextrin/cornstarch, cornstarch, and
      sucrose/cornstarch) and across genders. This consistent effect of melatonin on
      the intake of carbohydrate-rich diets with contrasting sensory attributes rules
      out the possibility that melatonin acts on sensorymotor pathways, thus suggesting
      that melatonin's effect on food intake is controlled by the carbohydrate content
      of the diet. In contrast, melatonin could be affecting some sensory or motor
      processes peculiar to the ingestion of protein since it increased protein-rich
      diet intake inconsistently across the various preparations (casein, soy isolate,
      and egg protein) as well as genders. This evidence supports the view that
      melatonin acts as a time indicator, reinforcing the animals with a "night cue",
      and favors predominant carbohydrate intake normally occurring at the beginning of
      the activity period.

PMID- 14568304
TI  - Relationship between wheel running, feeding, drinking, and body weight in male
      rats.
AB  - The amount of wheel running varies widely between rats. Wheel introduction and
      running also have profound effects on the animal's energy balance. We explored
      the effects of ad lib wheel access and running levels on feeding, drinking, and
      body weight in 30 young adult male rats with wheel access and in 30 rats without
      wheel access. The initial running period (Days 1-8) and a time of stable running
      [Days 29-32 (DEnd)] were analyzed using both between- and within-group
      approaches. Initially, wheel access suppressed feeding (by about 25% over the 8
      days) but not drinking. There were no significant correlations between the amount
      of wheel running and the other behaviors. The degree of feeding suppression was
      also not correlated to the amount of running. When running had stabilized (animal
      ran from 841 to 13,124 wheel turns per day), food intake was increased by about
      0.75 g per 1000 wheel turns. Running at this time correlated positively with
      feeding and drinking and negatively with body weight and weight gain. In animals
      without wheel access, feeding and drinking were positively correlated with weight
      and weight gain, but in animals with wheel access, these correlations were close
      to zero. Only early running predicted later levels of running but accounted for
      only 23% of the variance in running. Wheel access has profound but very different
      immediate and long-term effects on the rats' energy balance.

PMID- 14568305
TI  - Age-related sex differences in spatial learning and basal forebrain cholinergic
      neurons in F344 rats.
AB  - Basal forebrain cholinergic neurons are important for spatial learning in
      rodents. Spatial learning ability is reportedly better in males than females, and
      declines with age. To examine the role of cholinergic function in sex- or age
      related differences in spatial learning, we compared the size of basal forebrain
      cholinergic neurons (BFCN) of young and aged male and female Fischer 344 (F344)
      rats that had been trained in the Morris water maze. Young male and female rats
      were equally proficient in finding the platform during training trials, but probe
      tests revealed that young male rats had better knowledge of the platform's
      precise location. Impairments in spatial learning were observed in aged rats, and
      the advantage of males over females was lost. BFCN were significantly larger in
      young male than young female rats, and were correlated with spatial memory
      performance for both groups. BFCN were smaller in aged than young males; no
      change was seen between young and aged females. In the groups of aged rats the
      correlation between neuron size and spatial memory was lost. The present findings
      provide further evidence of a role for the basal forebrain cholinergic system in
      spatial learning, but reveal a complex interaction between sex, age and
      behavioral performance.

PMID- 14568307
TI  - Involvement of the telencephalon in spaced-trial avoidance learning in the
      goldfish (Carassius auratus).
AB  - Goldfish (Carassius auratus) received escape-avoidance training in a shuttle
      response situation at a rate of a single trial per day. Widely spaced training
      evaluates the ability of a discriminative stimulus to control an avoidance
      response in the absence of stimulus carry-over effects from prior recent trials.
      In Experiment 1, master goldfish exhibited significantly faster avoidance
      learning than yoked controls. The results suggest that the shuttle response was
      instrumentally acquired. Experiment 2 demonstrated a significant deficit in the
      acquisition of avoidance behavior following ablation of the telencephalon. The
      implications of spaced-trial, telencephalon-dependent avoidance learning, as
      demonstrated in these experiments for the first time, are discussed in the
      context of comparative research on instrumental learning in goldfish. These
      results provide further support for the hypothesis that the fish telencephalon
      contains an emotional system that is critical for fear conditioning.

PMID- 14568306
TI  - Palatability, food intake and the behavioural satiety sequence in male rats.
AB  - Food intake is influenced not only by nutritional status but also by diverse
      environmental factors. Indeed, a unique quality of food reward is its strong
      modulation by palatability cues, such as taste, with animals generally preferring
      diets that are sweet and avoiding those that are either bitter or sour. As
      appetite suppressants (including those currently in development) could alter food
      intake by modifying taste sensitivity and/or palatability, the aim of the present
      study was to characterise the influence of taste adulteration on the normal
      structure of feeding behaviour, i.e., the behavioural satiety sequence (BSS).
      Adult male rats were initially habituated both to the basic test diet (mash) and
      the test arena. Following stabilisation of basal intake, a continuous monitoring
      technique was used to profile behaviour in weekly 1-h sessions during which the
      animals were presented, in counterbalanced order, with the basic diet (control)
      or one of four taste-adulterated variants (0.015% quinine, 0.04% quinine, 0.2%
      saccharin, 0.3% saccharin). Food intake was strongly suppressed by the higher
      quinine concentration but was not significantly altered by any of the other
      additives. Behavioural analysis revealed that this anorectic-like response to
      0.04% quinine-adulterated food was associated with a significant reduction in the
      peak feeding response, highly atypical intermittent food sampling/digging and the
      virtual absence of resting behaviour. Importantly, this pattern of behavioural
      change is readily distinguishable from those seen in response to other
      manipulations that reduce intake, including selective anorectics, sedatives and
      psychostimulants. Despite the lack of significant effect on food intake or the
      duration of feeding behaviour, dietary adulteration with 0.015% quinine (and, to
      a lesser degree, 0.3% saccharin) produced some effects on behavioural
      structure/time course consistent with a mild aversive response, i.e., bouts of
      midsession food sampling and a delay in the transition from eating to resting.
      Data are discussed in relation to the specific behavioural signature to quinine
      induced anorexia and its potential utility in identifying appetite suppressants
      that may modify intake via changes in taste sensitivity and/or palatability.

PMID- 14568308
TI  - Chronic psychosocial stress persistently alters autonomic function and physical
      activity in mice.
AB  - We investigated heart rate (HR), temperature (T), and physical activity (Act) (by
      means of radiotelemetry) in male mice subjected to chronic psychosocial stress.
      Resident/intruder dyads lived in sensory contact for 15 days with the possibility
      to physically interact daily during the light phase for a maximum of 15 min.
      Intruders becoming dominants (InD) or subordinates (InS) were investigated here.
      The aims were to investigate; if a daily aggressive interaction would result in
      adaptation of autonomic responses; the effects of the social stress on daily
      rhythmicity and the way these effects change over time; whether acute and long
      term autonomic changes do correlate; to compare dominants and subordinates. InD
      and InS showed a strong autonomic activation during the interactions, with
      moderate (InS) or no (InD) habituation over time. On the long term, InD showed
      tachycardia and marked hyperthermia but normal physical activity, while InS
      showed tachycardia, slight hyperthermia, and depressed physical activity. No
      correlation emerged between the acute and the long-term autonomic responses.
      These results highlight the existence of a sustained autonomic activation under
      chronic stress, which was also affected by mice social status.

PMID- 14568309
TI  - Response to thermal stress and personality.
AB  - Tolerance to cold and heat exposure shows large variations for which there is
      still insufficient explanation. On the other hand the relationship between the
      responses to mental stress and individual personality is well documented. The aim
      of this study was then to find if personality traits have some influence on the
      responses to environmental temperature exposure. A group of 20 young adults were
      exposed for 90 min to cold (10 degrees C) while skin temperature (Ts), oxygen
      consumption and discomfort rating were recorded. In a second experiment they were
      exposed to heat (40 degrees C) for 90 min when the sweat rate and the discomfort
      rating were recorded. Prior to these tests the Big Five Personality Test was used
      to measure the personality traits of the subjects. The results show significant
      negative correlation between neuroticism and the O(2) consumed, the discomfort
      rating and Ts for the test in the cold, while extraversion was positively related
      to O(2) consumption but not to Ts and discomfort rating. In response to heat,
      neuroticism predominance was associated with greater discomfort, reduced
      tolerance and diminished sweat rate. The discomfort rating, in this case, was
      negatively related to extraversion. It is proposed that the reduced O(2)
      consumption in the cold and the lower rate of sweating in the heat observed with
      neuroticism, are caused by enhanced activity of the sympathetic nervous system.
      Further investigation is required to assess the validity of this proposal.
      Overall, the present investigation shows that physical environmental stresses, in
      common with mental stress, could be in some ways related to personality traits.

PMID- 14568310
TI  - A nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methyl ester, attenuates
      lipoprivic feeding in mice.
AB  - Possible involvement of nitric oxide (NO) in lipoprivic feeding was investigated
      in nondeprived male ICR mice adapted to a high-fat diet in a within-subjects
      design. Lipoprivation was induced by blocking fatty acid oxidation with Na
      mercaptoacetate (MA), which produces a short-term increase in feeding in mice and
      rats. Food intake, measured at 1, 2, and 4 h following injection of 70 mg/kg of
      MA, was attenuated in a dose related manner with increasing pretreatment dose
      (1,10, 25 and 50 mg/kg sc) of the NO-synthase (NOS) inhibitor, N(G)-nitro-L
      arginine methyl ester (L-NAME), reaching statistical significance at 10 mg/kg of
      L-NAME at h1 when compared to vehicle control condition. The inactive isomer, D
      NAME, was ineffective, thereby supporting stereospecific drug action and directly
      implicating NO. A control experiment measured general locomotor activity (grid
      crossings and rears) in an open arena under 10-50 mg/kg of L-NAME in the same
      mice; both measures were significantly different from vehicle condition only at
      the highest dose. These findings support involvement of NO in lipoprivic
      hyperphagia; they are consistent with and extend research linking NO and
      ingestive behaviors through use of NOS inhibitors. Possible influences of
      confounds were discussed.

PMID- 14568311
TI  - Characterization of 50-kHz ultrasonic vocalizations in male and female rats.
AB  - Male and female rats emit ultrasonic vocalizations in reproductive encounters.
      While estrous bedding has been used to elicit vocalizations of males, the number
      of responses is variable. We report a reliable method to assess vocalizations
      using exposure to a stimulus animal. The stimulus rat is placed behind a wire
      barrier for 5 min, then removed. Vocalizations are then recorded for 5 min.
      Experiment 1 validated this method and it was used for subsequent experiments. In
      Experiment 2, male rats were castrated and tested for the restoration of
      vocalizations. In one group, males were allowed to copulate freely; in the other,
      females had vaginal masks to prevent ejaculation, but not mounting. Vocalizations
      were restored only in males allowed to ejaculate. In Experiment 3, we measured
      vocalizations in sexually nai;ve and sexually experienced males following
      exposure to either castrated (CAS) males, testosterone (T)-treated males,
      ovariectomized (OVX) females, or OVX females receiving estrogen plus progesterone
      (E+P). Males vocalized most after exposure to E+P females, whether they were
      sexually experienced or naive. However, the rate of vocalizations was
      significantly higher after exposure to E+P females when the males were sexually
      experienced. In Experiment 4, we measured vocalizations in females following
      exposure to CAS males, T-treated males, OVX females, or E+P females. Females
      vocalized most after exposure to T-treated males. Our results show that (1)
      sexual experience facilitates vocalizations in male rats, (2) vocalizations are
      highest after exposure to hormonally receptive conspecifics, and (3) ultrasonic
      signaling is a sensitive index for assessing the hormonal disposition of
      conspecifics.

PMID- 14568312
TI  - Wheel running produces conditioned food aversion.
AB  - Previous investigations of conditioned taste aversion (CTA) induced by wheel
      running have used flavored liquids such as conditioned stimuli (CSs). Assuming
      that classical conditioning mediates activity anorexia, it is expected that CTA
      induced by physical activity should extend to food stimuli. The main purpose of
      the present experiment was to investigate this possibility. Rats were given a 60
      min access to a running wheel [unconditioned stimulus (US)] either before or
      after being exposed to a novel distinctive flavored food (CS). An additional
      group had access to running wheels 4 h after receiving the CS food. Results from
      the present experiment indicate that regimented and contingent periods of wheel
      running decrease consumption of a food available before wheel running in
      nondeprived rats.

PMID- 14568313
TI  - Forebrain c-fos expression under conditions conducive to pair bonding in female
      prairie voles (Microtus ochrogaster).
AB  - Repeated mating over a period of 6 h facilitates pair-bond formation in
      monogamous prairie voles. Using this paradigm, we examined fos expression in
      brain areas implicated in social behavior in voles. We hypothesized that the
      presence of the fos protein after a period of time sufficient for pair bonding to
      occur may indicate brain areas that are especially important in pair bond
      formation. We found elevated levels of fos immunoreactivity in the medial and
      cortical amygdala, medial preoptic area (MPOA), and bed nucleus of the stria
      terminalis (BNST) in females that mated several times over a 6-h period as
      compared to a variety of unmated controls. No treatment effects were found in the
      central amygdala, nucleus accumbens (NAcc), or lateral septum (LS). We suggest
      that areas that show evidence of fos expression after sufficient time for pair
      bonding to occur may be important in the formation of associations between the
      partner and mating stimuli.

PMID- 14568314
TI  - Emotional fever after habituation to the temperature-recording procedure.
AB  - To examine whether habituation to having temperatures taken might reduce the
      emotional fever induced by other stressors, 20 rats were habituated by having
      three colonic temperatures taken within 6 min twice a week for 8 weeks. Two novel
      stressors were added during Week 9; rats were given an intraperitoneal saline
      injection before taking their temperatures on Day 1, and on a second day, they
      were housed with a group of unfamiliar animals for 5 min before taking their
      temperatures. Temperatures during Weeks 10-11 were taken as during Weeks 1-8.
      Results showed that, overall, the third daily temperature averaged 1 degrees C
      higher than the first, indicating that taking temperatures was stressful. Between
      weeks, temperatures rose between Weeks 1 and 2, suggesting a conditioned fever.
      Temperatures fell 1.5 degrees C from Weeks 2-8, indicating habituation. During
      Week 9, temperatures after the intraperitoneal injection were no higher than
      during Week 8; however, 5 min of group housing raised temperatures 1.5 degrees C
      for males and 2.5 degrees C for females. Temperatures during Weeks 10 and 11 were
      below those of Week 8, suggesting that the fever induced by group housing in Week
      9 was situation specific. These results indicate that rats habituated to having
      their temperatures taken exhibit emotional fever only to selected new stimuli.
      Body temperatures do not rise after an intraperitoneal injection given by a
      familiar handler, but briefly placing rats with unfamiliar animals induces a
      substantial febrile response.

PMID- 14568315
TI  - In vivo basal and amphetamine-induced striatal dopamine and metabolite levels are
      similar in the spontaneously hypertensive, Wistar-Kyoto and Sprague-Dawley male
      rats.
AB  - Nigrostriatal alterations are proposed to partially underlie the hypertension and
      hyperactivity exhibited by the spontaneously hypertensive rat (SHR). Here, in
      vivo microdialysis was used to measure baseline and d-amphetamine (AMPH)
      stimulated striatal dopamine (DA) and metabolite levels in adult male SHR, Wistar
      Kyoto (WKY), and Sprague-Dawley (SD) rats. At approximately 19 weeks of age,
      baseline levels of DA, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid
      (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) were measured after which time,
      each rat was injected intraperitoneally with 2 mg/kg AMPH and samples were
      collected for the subsequent 200 min. There were no significant strain
      differences in baseline levels of DA, HVA, and 5-HIAA. The baseline level of
      DOPAC was decreased in the WKY relative to the SD. AMPH treatment altered DA,
      DOPAC, HVA, and 5-HIAA to a similar extent in all strains; thus, there were no
      significant strain differences, nor did the area under the curve (AUC) for DA
      levels differ between strains. AUC for DOPAC was significantly smaller for the
      WKY relative to the SD strain, likely due to the lower baseline level. At the
      single dose of amphetamine used here, the results indicate that in vivo DA levels
      in the SHR are similar to the WKY and SD strains.

PMID- 14568316
TI  - Cardiovascular responses elicited during binge administration of cocaine.
AB  - Cocaine use is often characterized by a repeated pattern of frequent
      administrations (binge) followed by periods of abstinence. The repeated binge
      administration of methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA)
      alters cardiovascular function and the arterial pressure and heart rate responses
      elicited by these drugs. Whether repeated binges of cocaine similarly affect
      cardiovascular function and cardiovascular responsiveness is unknown.
      Radiotelemetry was used to record the cardiovascular responses elicited during
      three successive cocaine binges (5 mg/kg, t.i.d., for 4 days) in conscious,
      unrestrained rats. Each binge was separated by a 10-day cocaine-free period. The
      effects of cocaine administration on vascular reactivity and vasovagal, Bezold
      Jarisch reflex function were also evaluated. The intravenous administration of
      cocaine increased both mean arterial pressure (MAP) and heart rate. The arterial
      pressure and heart rate responses elicited by cocaine, both within and between
      the binges, were remarkably similar. The arterial pressure and heart rate
      responses elicited by the intravenous administration of sodium nitroprusside,
      acetylcholine and phenylephrine before each binge and 10 days after the last
      binge were not altered after the binge administration of cocaine. Likewise,
      Bezold-Jarisch reflex function elicited by intravenous serotonin was unchanged
      after the binge administration of cocaine. These results indicate that the
      administration of cocaine using this repeated binge model does not alter the
      arterial pressure and heart rate responses elicited by the drug, nor does it
      alter the cardiovascular responses elicited by a variety of vasoactive
      substances.

PMID- 14568317
TI  - Extreme reduction of dipeptidyl peptidase IV activity in F344 rat substrains is
      associated with various behavioral differences.
AB  - The enzyme and binding protein dipeptidyl peptidase IV (DPPIV/CD26) has a unique
      enzymatic specificity in cleaving dipeptides from neuropeptides, chemokines, and
      hormones. Thus, DPPIV is potentially involved in the regulation of functions of
      the immune, endocrine, and nervous systems. In the present study, we compared
      DPPIV-deficient, mutant Japanese [F344/DuCrj(DPPIV-)] and German
      [F344/Crl(Ger/DPPIV-)] F344 rat substrains with a wild-type-like F344 substrain
      [F344/Crl(Por)] from the United States in a multitiered strategy using a number
      of different behavioral tests. General health, neurological and motor functions,
      and sensory abilities of the different F344 substrains were not different. A
      reduced body weight and a reduced water consumption were observed in mutant
      animals. DPPIV-deficient rats exhibited increased pain sensitivity in a non
      habituated hot plate test, indicative of a reduced stress-induced analgesia. In
      line with this finding, reduced stress-like responses in tasks like the open
      field (OF), social interaction (SI), and passive avoidance test were found.
      Differences in DPPIV-like activity appear to be involved in neurophysiological
      processes because DPPIV-deficient animals were less susceptible to the sedative
      effects of ethanol. The varying phenotypes of the F344 substrains are likely to
      be mediated by differential degradation of DPPIV substrates such as substance P,
      glucagon-like peptide (GLP)-1, enterostatin, and especially neuropeptide Y (NPY).
      Potentially, DPPIV-deficient substrains represent an important tool for
      biomedical research, focusing on the involvement of DPPIV and its substrates in
      behavioral and physiological processes.

PMID- 14568318
TI  - Early exposure to oxytocin affects the age of vaginal opening and first estrus in
      female rats.
AB  - Neonatal exposure to exogenous oxytocin (OT) can have long-term effects on the
      subsequent expression of adult behavior and physiology. Here, we test the
      prediction that early postnatal exposure to OT can affect the timing of sexual
      maturation in females, as indicated by the age of vaginal opening and the onset
      of first estrus. To test this hypothesis, female Sprague-Dawley rats received one
      of four treatments beginning on the day of birth and continuing for the next 6
      days. Three groups received an intraperitoneal injection of one of the following:
      OT (1 mug/g), an OT antagonist (OTA, 0.1 mug/g) or isotonic saline (vehicle
      control). The fourth group was handled but not injected. Females were then
      examined to determine the day of vaginal opening and first estrus. The potential
      effects of OT on body weight were also measured, with females being weighed on
      postnatal days 1-7, 70, 91 and 136. Treatment with OT significantly delayed the
      age of vaginal opening and the onset of first estrus. There was no effect on
      weight. Results indicate that early exposure to OT can affect the timing and
      development of female sexual maturation.

PMID- 14568319
TI  - Central nNOS is involved in restraint stress-induced fever: evidence for a cGMP
      pathway.
AB  - It has been shown that the NO pathway plays a major role in restraint stress
      induced fever, and that the neuronal nitric oxide synthase (nNOS) seems to be the
      NOS isoform that accounts for the pyretic effect of NO in psychological stress
      induced fever. However, no information exists as to localization of the nNOS,
      i.e., in the peripheral or in the central nervous system (CNS). Thus, in the
      present study, we tested the hypothesis that NO arising from nNOS in the CNS
      participates in restraint stress-induced fever. Moreover, we also assessed the
      involvement of cyclic guanosine monophosphate (cGMP) in the mediation of the NO
      effects. To this end, intracerebroventricular S-methyl-L-thiocitrulline (SMTC; a
      selective nNOS inhibitor), sodium nitroprusside (an NO donor) or Rp-guanosine
      3',5'-cyclic monophosphothioate triethylamine (Rp-cGMPS; a specific membrane
      permeable inhibitor of the activation by cGMP of cGMP-dependent protein kinase)
      were injected, and the colonic temperature (T(c)) of restrained or unrestrained
      rats was recorded. Both SMTC (0.5 mg/mul) and Rp-cGMPS (10 mug/mul)
      intracerebroventricular injections enhanced restraint fever, whereas
      intracerebroventricular injections of sodium nitroprusside (100 mug/mul) reduced
      this response. These data indicate that NO produced in the CNS, arising from nNOS
      and acting via cGMP, plays an antipyretic role in the restraint stress-induced
      fever.

PMID- 14568320
TI  - Pregnant female guinea pigs adapt easily to a new social environment irrespective
      of their rearing conditions.
AB  - For male guinea pigs, the social rearing conditions are crucial for the course of
      social interactions and endocrine stress responses in later life. While colony
      reared males adjust easily to new social situations, high levels of aggression
      and extreme endocrine responses are found in males that were raised in pairs
      [Psychoneuroendocrinology 23 (1998) 891]. This study investigated whether the
      same finding also applies to females. Therefore, 8 females reared in mixed-sexed
      colonies of 8-10 males and 12-13 females (designated as CF) and 8 females reared
      in mixed-sexed pairs (designated as PF) were transferred to an unknown colony for
      3 days. Control females remained in their respective housing conditions. Serum
      cortisol concentrations (CORT) were determined before, during and after the
      transfer. The behavior of the CF and PF was recorded on the first, second and
      third day of transfer. All females adjusted easily to the new social situation,
      but frequencies of some behavioral patterns were significantly different between
      CF and PF. In the new social situation, PF displayed social orientation as well
      as defensive aggressive and avoidance behavior more frequently than CF. On the
      day of transfer, resident males displayed courtship behavior more frequently
      towards PF than CF. CORT did not differ between PF and CF either before, during
      or after the transfer. Furthermore, the transfer to the new social situation did
      not result in significantly increased CORT 4 h later either in CF or PF. We
      conclude that-in contrast to male guinea pigs-females are able to adapt to
      unfamiliar conspecifics independently of their social rearing conditions.

PMID- 14568321
TI  - Sexual and olfactory preference in noncopulating male rats.
AB  - In some species including rats, mice, gerbils, and rams, apparently normal males
      fail to copulate when repeatedly tested with receptive females. These animals are
      called "noncopulators (NC)," and the cause of this behavioral deficit is unknown.
      It has been shown that NC rats do not have hormonal alterations or deficits in
      the mechanisms that control penile function. The present study was designed to
      examine (Experiment 1) whether NC male rats prefer receptive females to sexually
      active males. In addition, the olfactory preference for bedding soiled from
      estrous or for anestrous bedding was investigated. These tests were performed in
      NC and copulating (C) male rats when the subjects were intact, gonadectomized
      (GDX), or GDX and treated with high doses of testosterone propionate (TP). Our
      results demonstrate that NC rats do not display sexual behavior even after high
      TP treatment. While C male rats have a clear preference for receptive females as
      opposed to a sexually active male, NC rats do not. In all hormonal conditions,
      the preference shown by NC rats for estrous bedding was significantly reduced in
      comparison to that seen in C rats. TP treatment in NC rats did not modify either
      partner or odor preference. In Experiment 2, we evaluated if NC rats are
      feminized and if it could be easier to induce feminine-like behavior by hormone
      treatment with estradiol benzoate (EB) or with EB plus progesterone (P) (EB+P).
      Odor preference for estrous or male bedding under these hormonal conditions was
      also compared. No differences between NC and C rats were found in feminine sexual
      behavior. In the olfactory test, we found that NC rats prefer odors from
      receptive females as opposed to male odors, but this preference is reduced
      compared to that of C rats. Males treated with EB or EB+P show no preference for
      female odors. These results demonstrate that treatment with EB or EB+P does not
      increase feminine sexual behavior in NC rats.

PMID- 14568323
TI  - Effects of pyruvate administration on infarct volume and neurological deficits
      following permanent focal cerebral ischemia in rats.
AB  - Recent experimental evidences indicate that pyruvate, the final metabolite of
      glycolysis, has a remarkable protective effect against different types of brain
      injury. The purpose of this study was to assess the neuroprotective effect and
      the neurological outcome after pyruvate administration in a model of ischemic
      stroke induced by permanent middle cerebral artery occlusion (pMCAO) in rats.
      Three doses of pyruvate (250, 500 and 1000 mg/kg, i.p.) or vehicle were
      administered intraperitoneally 30 min after pMCAO. In other set of experiments,
      pyruvate was given either before, immediately after ischemia or in a long-term
      administration paradigm. Functional outcome, mortality and infarct volume were
      determined 24 h after stroke. Even when the lowest doses of pyruvate reduced
      mortality and neurological deficits, no concomitant reduction in infarct volume
      was observed. The highest dose of pyruvate increased cortical infarction by 27%
      when administered 30 min after pMCAO. In addition, when pyruvate was given before
      pMCAO, a significant increase in neurological deficits was noticed. Surprisingly,
      on the contrary of what was found in the case of transient global ischemia,
      present findings do not support a great neuroprotective role for pyruvate in
      permanent focal cerebral ischemia, suggesting two distinct mechanisms involved in
      the effects of this glycolytic metabolite in the ischemic brain.

PMID- 14568324
TI  - Reassessment of parameters for applying motor-unit triggered stimuli in peri
      stimulus time histograms.
AB  - We reassessed the response properties of peri-stimulus time histograms (PSTHs) in
      cases when a test stimulus was triggered by a motor-unit discharge with a
      constant delay time. In this experiment, single motor unit action potentials were
      recorded from the right tibialis anterior (TA) muscle of five healthy persons. A
      test stimulus of the common peroneal nerve with low intensity to activate only Ia
      afferents of the TA was applied through a bipolar stimulating electrode placed
      distal to the neck of the fibula. We obtained several PSTHs with various delay
      times and stimulus intensities in the same recording session for maintaining the
      background property as the same among the test situations. As a result, we
      confirmed three characteristics of PSTHs from observed data: (1) given the same
      delay time (the same background firing properties), a weaker stimulus intensity
      evokes a lessened effect on PSTHs, naturally; (2) delay time alters the induction
      balance of direct and indirect effects on PSTHs even if the stimulus intensity is
      the same because the background firing properties are different; and (3) response
      probabilities do not correspond directly to stimulus intensities when background
      firing properties are different; it is possible for a relatively strong intensity
      stimulus to produce a weaker effect than a weak stimulus. We concluded that
      comparisons of effects taken at different phases in the control distribution (and
      also effects taken from different control distributions or different motor units)
      can be misleading. Therefore, such comparisons should only be made within data
      obtained from the same phase in the same control distribution of the same motor
      unit.

PMID- 14568325
TI  - Neuroprotective and neurotoxic effects of estrogens.
AB  - The ovarian hormone 17beta-estradiol (E2) is neuroprotective in animal models of
      neurodegenerative diseases. Some studies suggest that the neuroprotective effects
      of 17beta-estradiol are a consequence of its antioxidant activity that depend on
      the hydroxyl group in the C3 position of the A ring. As in other tissues, 17beta
      estradiol is metabolized in the brain to 2-hydroxyestradiol (2OHE2) and 2
      methoxyestradiol (2MEOHE2). These two molecules present the hydroxyl group in the
      A ring and have a higher antioxidant activity than 17beta-estradiol. To test the
      hypothesis that conversion to 2-hydroxyestradiol and 2-methoxyestradiol may
      mediate neuroprotective actions of 17beta-estradiol in vivo, we have assessed
      whether these molecules protect hilar hippocampal neurons from kainic acid
      toxicity. Ovariectomized Wistar rats received an i.p. injection of 1, 10 or 100
      microg 17beta-estradiol, 2-hydroxyestradiol or 2-methoxyestradiol followed by an
      i.p. injection of kainic acid (7 mg/kg) or vehicle. Treatment with kainic acid
      resulted in a significant loss of hilar neurons. Only the highest dose tested of
      17beta-estradiol (100 microg/rat) prevented kainic acid-induced neuronal loss. 2
      Hydroxyestradiol and 2-methoxyestradiol did not protect hilar neurons from kainic
      acid, suggesting that the mechanism of neuroprotection by 17beta-estradiol in
      vivo is not mediated by its metabolism to catecholestrogens or
      methoxycatecholestrogens. Furthermore, 2-methoxyestradiol (100 microg/rat), by
      itself, resulted in a significant neuronal loss in the hilus that was detected 96
      h after the treatment with the steroid. This finding suggests that endogenous
      metabolism of 17beta-estradiol to 2-methoxyestradiol may counterbalance the
      neuroprotective effects of the hormone.

PMID- 14568326
TI  - The effects of protein kinase C activity on synaptic transmission in two areas of
      rat hippocampus.
AB  - The effects of three protein kinase C (PKC) agonists (phorbol ester, ingenol and
      indolactam-V) and two PKC antagonists (D-erythro-sphingosine and chelerythrine)
      on input-output (I-O) relations in the Schaffer collateral pathway to CA1 (SC
      CA1) and mossy fiber pathway to CA3 (MF-CA3) were determined in rat hippocampus
      brain slices. In the SC-CA1 pathway, phorbol esters and indolactam-V had only
      small effects on field excitatory post-synaptic potentials (fEPSP) in slices from
      60-day animals, although ingenol, an activator of novel PKC isozymes, caused a
      significant decrease of the field excitatory post-synaptic potentials amplitude
      in 60-day animals, but not in 30-day animals. In contrast, in the MF-CA3 pathway,
      PKC agonists induced a significant increase in the field excitatory post-synaptic
      potentials. PKC antagonists depressed the field excitatory post-synaptic
      potentials in the SC-CA1 pathway, but had no significant effect in the MF-CA3
      pathway. In the MF-CA3 pathway, paired-pulse facilitation was abolished by PKC
      agonists and unaffected by antagonists. In SC-CA1, it was depressed by agonists
      to levels below control, whereas it was significantly increased by chelerythine.
      We conclude that PKC plays important but different roles in both regions. In the
      SC-CA1 pathway, PKC is almost maximally active under control circumstances, and
      PKC antagonists significantly reduce synaptic responses. In contrast, in the MF
      CA3 pathway, there is no apparent activation under resting circumstances, but
      significant potentiation of synaptic transmission is induced when PKC is
      activated. There are developmental changes in the pattern of PKC isozymes, and
      both pre- and post-synaptic actions are important.

PMID- 14568327
TI  - Development of levodopa-induced dyskinesias in parkinsonian monkeys may depend
      upon rate of symptom onset and/or duration of symptoms.
AB  - Levodopa-induced dyskinesias (LIDs) present a major problem for the long-term
      management of Parkinson's disease (PD) patients. Due to the interdependence of
      risk factors in clinical populations, it is difficult to independently examine
      factors that may influence the development of LIDs. Using macaque monkeys with
      different types of MPTP-induced parkinsonism, the current study evaluated the
      degree to which rate of symptom progression, symptom severity, and response to
      and duration of levodopa therapy may be involved in the development of LIDs.
      Monkeys with acute (short-term) MPTP exposure, rapid symptom onset and short
      symptom duration prior to initiation of levodopa therapy developed dyskinesia
      between 11 and 24 days of daily levodopa administration. In contrast, monkeys
      with long-term MPTP exposure, slow symptom progression and/or long symptom
      duration prior to initiation of levodopa therapy were more resistant to
      developing LIDs (e.g., dyskinesia developed no sooner than 146 days of chronic
      levodopa administration). All animals were similarly symptomatic at the start of
      levodopa treatment and had similar therapeutic responses to the drug. These data
      suggest distinct differences in the propensity to develop LIDs in monkeys with
      different rates of symptom progression or symptom durations prior to levodopa and
      demonstrate the value of these models for further studying the pathophysiology of
      LIDs.

PMID- 14568328
TI  - Nicorandil prevents oxidative stress-induced apoptosis in neurons by activating
      mitochondrial ATP-sensitive potassium channels.
AB  - Nicorandil, a clinically useful drug for the treatment of ischemic heart disease,
      has an anti-apoptotic effect in cardiomyocytes, and activation of mitochondrial
      ATP-sensitive potassium (mitoKATP) channels underlies this effect. Recently,
      several studies showed that nicorandil reduced brain injury in animal models of
      brain ischemia. Based on these facts, we hypothesized that nicorandil may have
      anti-apoptotic effects in neurons mediated by mitoKATP channels. We investigated
      the effect of nicorandil on apoptosis induced by oxidative stress using cultured
      cerebellar granule neurons. Nicorandil (100 micromol/l) significantly suppressed
      the number of cells with TUNEL-positive nuclei and the increase in caspase-3
      activity induced by 20 micromol/l H2O2. An indicator dye for mitochondrial inner
      membrane potential (DeltaPsim) revealed that nicorandil prevented the loss of
      DeltaPsim induced by H2O2 in a concentration-dependent manner. These effects were
      abolished by 5-hydroxydecanoate (5HD; 500 micromol/l), a mitoKATP channel
      blocker. The present results showed that nicorandil has anti-apoptotic effects in
      neurons, at least in part, by preserving DeltaPsim.

PMID- 14568329
TI  - Increased ability to induce long-term potentiation of spinal dorsal horn neurones
      in monoarthritic rats.
AB  - Long-term potentiation (LTP) of transmission of impulses in unmyelinated (C
      fibre) primary afferents by prior tetanic conditioning stimulation has been
      demonstrated in the dorsal horn of the spinal cord. Since this potentiation has
      been proposed to be relevant to the increased responsiveness of spinal neurones
      associated with peripheral inflammation (central sensitisation), the present
      experiments compared the induction of LTP in normal rats and rats with
      monoarthritis. Monoarthritis was induced by injection of complete Freund's
      adjuvant (CFA) into the left ankle joint of 12 rats. All animals showed
      behavioural signs of thermal hyperalgesia and were used for electrophysiological
      experiments after 4-8 days. In each animal, extracellular recordings were
      obtained from a single, wide dynamic range (WDR) dorsal horn neurone. High
      frequency tetanic conditioning stimulation of the sciatic nerve gave varying
      effects on the C-fibre-evoked responses of neurones in the normal rats, with
      potentiation in two, no change in five and a depression in five. By contrast,
      conditioning stimulation in rats with inflammation produced a long-lasting
      potentiation of C-fibre-evoked responses in 11 out of 12 neurones, with no effect
      in one. The ease with which LTP was induced in animals with inflammation supports
      the proposal that the underlying mechanisms of LTP are similar to those of the
      central sensitisation associated with peripheral inflammation.

PMID- 14568330
TI  - Estrogen-induced neurochemical and electrophysiological changes in the
      parabrachial nucleus of the male rat.
AB  - Estrogen has previously been shown to significantly change sympathetic and
      parasympathetic system output via an action within the central nuclei responsible
      for regulating autonomic tone. These estrogen-induced changes were observed
      within 30 min of systemic administration and could be blocked by the direct
      microinjection of the estrogen receptor antagonist, ICI 182780, into the
      parabrachial nucleus (PBN) of the pons. In the present investigation, we sought
      to determine the possible mechanism(s) by which estrogen produced these rapid
      changes in autonomic tone by determining if estrogen modulates neuronal
      excitability within the PBN. Male Sprague-Dawley rats were anaesthetized with
      Inactin (sodium thiobutabarbitol, 100 mg/kg) and instrumented for the intravenous
      injection of estrogen and placed in a stereotaxic frame for the insertion of a
      microdialysis probe or glass recording electrode into the PBN. In the first
      experiment, we sought to determine the local concentration of estrogen in the
      cerebrospinal fluid in the PBN following systemic injection of estrogen. In the
      second experiment, we sought to determine the functional significance of systemic
      estrogen injection on neuronal activity and amino acid neurotransmitter levels in
      the PBN. Systemic estrogen injection resulted in a significant increase in local
      estrogen concentration in the PBN which corresponded to a decrease in neuronal
      excitability and extracellular glutamate levels while increasing GABA levels in
      the PBN. These results suggest that estrogen decreases neuronal excitability in
      the PBN by modulating synaptic transmission via an increased release of GABA and
      a decreased release of glutamate.

PMID- 14568331
TI  - The free radical spin-trap alpha-PBN attenuates periinfarct depolarizations
      following permanent middle cerebral artery occlusion in rats without reducing
      infarct volume.
AB  - The effect of the free radical spin-trap alpha-phenyl-butyl-tert-nitrone (alpha
      PBN) in permanent focal cerebral ischemia in rats was examined in two series of
      experiments. In the first, rats were subjected to permanent occlusion of the
      middle cerebral artery (MCAO) and treated 1 h after occlusion with a single dose
      of alpha-PBN (100 mg/kg) or saline. Body temperature was measured and controlled
      for the first 24 h to obtain identical temperature curves in the two groups.
      Cortical infarct volumes were determined on histological sections 7 days later.
      alpha-PBN did not significantly reduce infarct volume (control: 28.3+/-16.3 mm3
      vs. alpha-PBN 23.7+/-7.4 mm3). In the second series of experiments, periinfarct
      depolarizations (PIDs) were recorded with an extracellular DC electrode at two
      locations in the ischemic penumbra for the initial 3 h following MCAO. alpha-PBN
      (100 mg/kg, single dose in conjunction with occlusion) significantly reduced the
      total number (median value of 3 PIDs in the control groups vs. 1 PID in alpha-PBN
      groups, p<0.001) and total duration of the PIDs (median value 662 s in the
      control groups vs. 162 s in the alpha-PBN groups, p<0.006). In spite of this,
      cortical infarct volumes determined 7 days later in the same rats were not
      smaller in alpha-PBN-treated rats. The study thus demonstrates that attenuation
      of PIDs does not always lead to smaller infarcts if permanent arterial occlusion
      is followed by long survival time and does not support the hypothesis that PIDs
      per se are critical determinants of infarct size in this situation.

PMID- 14568332
TI  - Evidence that nitric oxide-glutamate cascade modulates spinal antinociceptive
      effect of morphine: a behavioural and microdialysis study in rats.
AB  - We evaluated the ability of spinally administered nitric oxide (NO) synthase
      inhibitor to modulate antinociceptive action of intrathecal (i.t.) morphine in
      rats by measuring the early and late phases of flinching and licking/biting in
      the formalin test. To determine the contribution of spinal NO and glutamate, we
      measured the release of NO metabolites (nitrite/nitrate) and glutamate from the
      spinal cord in rats, using a microdialysis probe placed in the lumbar space. The
      i.t. administration of NG-nitro L-arginine methyl ester (L-NAME) produced a dose
      dependent reduction in the number of flinches during the late phase, whereas
      there were no significant alterations in the late phase licking/biting, and early
      phase flinching and licking/biting. Spinal administration of morphine at low
      doses produced a significant antinociceptive activity in the early and late
      phases of the flinching behaviour, whereas higher doses of morphine were required
      to obtain a significant effect in the licking/biting behaviour during both
      phases. Combination of L-NAME with morphine resulted in an enhanced reduction in
      the early and late phase flinching. Enhanced antinociceptive activity was
      observed in the late phase licking/biting by i.t. combined administration of L
      NAME (400 nmol) and morphine (1.25 nmol). In the present study, we have confirmed
      our prior results that injection of formalin (5.0%) into the plantar surface of
      the paw evoked a biphasic spinal release of nitrite/nitrate and a transient
      release of glutamate. Formalin-evoked release of nitrite/nitrate and glutamate
      was also reduced markedly by i.t. combined administration of L-NAME and morphine.
      These behavioural and biochemical results suggest that i.t. administered L-NAME
      may enhance morphine-induced antinociception through an increased inhibition of
      nitrite/nitrate and glutamate releases evoked by formalin injection at the spinal
      cord level.

PMID- 14568333
TI  - Aging, estradiol and time of day differentially affect serotonin transporter
      binding in the central nervous system of female rats.
AB  - Estrogen-related changes in serotonergic neuronal transmission, including changes
      in the number of serotonin transporter (SERT) binding sites, have been cited as a
      possible cause for changes in mood, memory and sleep that occur during the
      menopausal transition. However, both aging and estradiol regulate SERT binding
      sites in the brain. The goal of this experiment was to determine how aging and
      estrogen interact to regulate SERT levels in the forebrain of young and
      reproductively senescent female Sprague-Dawley rats using [3H]paroxetine. The
      density of specific [3H]paroxetine binding in various brain regions was compared
      in young (2-4 months) and reproductively senescent (10-12 months) female rats at
      three times of day. In most brain regions examined, estrogen and aging
      independently increased the number of [3H]paroxetine binding sites. The only
      region that displayed a reduction in [3H]paroxetine binding with age was the
      suprachiasmatic nucleus (SCN). Time of day influenced [3H]paroxetine binding in
      the SCN and the paraventricular thalamus (PVT), two regions known to be involved
      in the regulation of circadian rhythms. Aging and/or estrogen also altered the
      pattern of binding in these regions. Thus, based on the results of this study, we
      conclude that aging and estrogen both act to regulate SERT binding sites in the
      forebrain of female rats, and that this regulation is region specific.

PMID- 14568334
TI  - Evaluation of the immortalised mouse brain capillary endothelial cell line,
      b.End3, as an in vitro blood-brain barrier model for drug uptake and transport
      studies.
AB  - Well-characterised cell lines represent important tools for the study of
      endogenous solute or xenobiotic transport. A brain microvascular cell line,
      b.End3, isolated from mice transformed with the Polyoma virus middle T-antigen is
      available commercially. Here we report the characterisation of some features of
      b.End3 of relevance to its use in blood-brain barrier transport investigations.
      The b.End3 cells displayed a distinctive spindle-like squamous morphology in
      culture. Clathrin coated pits and numerous uncoated intracellular vesicles were
      evident within the cells, as was the expression of the vesicle-associated
      proteins, clathrin, caveolin-1, flotillin and dynamin II. In the presence of C6
      astroglial co-culture b.End3 monolayers achieved a maximal transendothelial
      electrical resistance of 130 Omega cm2, but lacked real discrimination with
      respect to the permeation of transcellular and paracellular probes, e.g.
      permeability coefficients (x 10(-6) cm s(-1)) for propranolol of approximately 23
      vs. 16 for sucrose. RT-PCR analysis confirmed the presence within the b.End3
      cells of mRNA transcripts for the following transporters: GLUT-1; MCT 1 and 2;
      OAT1; Oatp1; mdr 1a and 1b; MRP 1 and 5; beta-alanine, system L and system y+L
      amino acid carriers; the nucleoside transporters cNT1 and 2, eNT1 and 2, and the
      tight junctional elements, ZO-1, JAM, occludin, claudin-1 and -5. The b.End3
      cells actively accumulated D-glucose in a sodium-independent manner with
      characteristics consistant with that of GLUT-1. Functionality for P-glycoprotein
      efflux was evident as assessed by a rhodamine-123 accumulation and retention
      assay. The system L LAT1/4F2hc amino acid transporter was examined through uptake
      of L-leucine and L-phenylalanine and provided Km and Vmax values of approximately
      16 microM and 350-480 pmol/mg protein/10 min, respectively; the affinity of
      transport for these substrates being weaker, approximately threefold, when the
      b.End3 cells were grown in the presence of C6 astroglial factors. Although the
      b.End3 cells appear unsuitable for transendothelial permeability assessments they
      display characteristics that would allow their worthwhile use in studies
      addressing blood-brain barrier transport mechanisms.

PMID- 14568336
TI  - Changes in intracellular calcium transients and LTP in the surround of visual
      cortex lesions in rats.
AB  - Injury and loss of neurons are observed in the center of a cerebral cortical
      lesion. Mechanisms of early functional reorganization post-lesion involve changes
      in the strength of synaptic coupling as measured in long-term potentiation (LTP).
      Since these changes in LTP may depend on the intraneuronal calcium concentration
      ([Ca2+]I), the present study analyzed the strength of synaptic LTP combined with
      measurements of the stimulus-induced peak calcium influx in slices from rat
      visual cortex in vitro. Slices were analyzed 1-7 days post-lesion by use of
      electrophysiological and calcium fluorescence imaging techniques. A theta-burst
      stimulus (TBS) was electrically applied to cortical layer IV, while changes in
      extracellular field potentials (FPs) and in the corresponding peak calcium influx
      were recorded in layers II/III. Both the strength of LTP and of the FP mediated
      peak calcium influx were significantly enhanced 1-6 days post-lesion at a
      distance of 4 mm from the lesion border. Pharmacological experiments revealed
      that the expression of LTP was dependent on the activation of NMDA receptors. The
      area of increased stimulus-evoked peak calcium influx correlated with the
      enhanced LTP, suggesting that changes in [Ca2+]I mediate the strength of long
      term synaptic plasticity following a cortical lesion. This mechanism may support
      synaptic reorganization in the surround of the deafferented region in rat visual
      cortex.

PMID- 14568335
TI  - The effect of morphine on MC4 and CRF receptor mRNAs in the rat amygdala and
      attenuation of tolerance after their blockade.
AB  - The relationships between the CRF, which enhances the proopiomelanocortin (POMC)
      biosynthesis, and POMC-derived peptides (opioids and melanocortins) might be a
      new target for rational treatment of morphine tolerance. In the present study, we
      investigated the effect of acute and chronic morphine administration on the level
      of CRF1 and melanocortin 4 receptor (MC4-R) mRNAs in the rat amygdala by
      quantitative real-time PCR method. Moreover, we investigated the effect of
      antagonists of melanocortin and CRF receptors, SHU9119 and alpha-helical CRF
      (alphah-CRF), respectively, administered bilaterally into the central nucleus of
      the amygdala, on morphine tolerance using tail-flick and paw withdrawal tests.
      Our study demonstrated that acute morphine administration decreased the level of
      MC4-R mRNA in the rat amygdala. This decrease was attenuated following chronic
      morphine administration, and mRNA level of MC4 receptors was gradually increased
      and, on 9th day of morphine administration, i.e. in the period when morphine
      tolerance already developed, the level was significantly increased in comparison
      with control and with the effect after single morphine dose. In contrast,
      morphine did not affect the CRF receptor. In behavioral study, we demonstrated
      that SHU9119 and alphah-CRF significantly increased the antinociceptive effect of
      morphine, when they were injected into the amygdala prior to morphine
      administration in tolerant rats. We have shown for the first time the
      contribution of amygdalar melanocortin receptors to morphine tolerance, and we
      conclude that the altered melanocortin receptor function may play an important
      role in the development of morphine-induced tolerance. CRF and melanocortin
      peptides can modulate the phenomena in the same direction, in opposition to
      opioids. Therefore, antagonists of melanocortin receptors may be regarded as
      possible therapeutic modulators of morphine tolerance.

PMID- 14568337
TI  - Secretion of tenascin-C by cultured astrocytes: regulation of cell proliferation
      and process elongation.
AB  - Tenascin-C (TNC), an extracellular matrix glycoprotein, is involved in tissue
      morphogenesis like embryogenesis, wound healing or tumorigenesis. Quiescent
      astroglia in long-term primary cultures are known to show rapid morphological
      changes after subculture and serum deprivation/re-addition (SSDR). To elucidate
      roles of TNC in the morphogenetic processes of cultured astrocytes, we have
      revealed morphological changes in association with soluble TNC contents in the
      medium and expression of TNC mRNA, TNC, glial fibrillary acidic protein (GFAP)
      and integrin beta1, one of its cell surface receptors, in glial cells after SSDR.
      Soluble TNC in the medium rapidly increased in amount at 4 h when GFAP-positive
      cells expressed TNC mRNA, TNC and integrin beta1. Cellular proliferation and
      growth occurred in colonies expressing TNC mRNA, TNC and integrin beta1 during
      the first 24 h. During the next 24 h, process elongation and cell migration
      occurred in association with increased GFAP expression and re-elevation of
      soluble TNC in the medium. Cell bodies became flat and larger with increased GFAP
      and reduced TNC expression at 72 h, while cultures became confluent with reduced
      GFAP and TNC expression at 96 h after SSDR. Functional blocking with anti-TNC
      antibody reduced cell proliferation and induced morphological change from a
      process-bearing slender shape to a flat and wide shape presumably due to
      increased cell adhesion. These findings strongly support the idea that endogenous
      TNC produced and released by astrocytes in response to serum stimulation induces
      their proliferation and process elongation through a paracrine/autocrine
      mechanism.

PMID- 14568338
TI  - Repair of amyloid beta(25-35)-induced memory impairment and synaptic loss by a
      Kampo formula, Zokumei-to.
AB  - Although Zokumei-to (ZMT), a Kampo formula, has been used for postapopletic
      sequelae such as paralysis and logopathy, only few studies of this drug have been
      carried out. We hypothesized that ZMT may affect neuronal plasticity and
      investigated whether or not this drug is capable of improving learning impairment
      and synaptic loss observed in patients with Alzheimer's disease (AD). Amyloid
      beta(25-35) [Abeta(25-35)] (4.7 nmol) was intracerebroventricularly injected into
      ddY mice (male, 6 weeks old). Fourteen days after the injection, mice were given
      ZMT extract (500 mg/kg/day) per os for 15 days. In a memory acquisition test, the
      Abeta(25-35)-injected mice required more time to master this task than did mice
      in the saline- or reverse peptide Abeta(35-25)-treated groups. ZMT-treated mice
      shortened escape latencies during trial days 3-5, but not significantly. Three
      days after the last drug treatment, a retention test was performed. Following
      ZMT, the number of crossings over a platform was significantly decreased in
      Abeta(25-35)-injected mice compared with those in the control groups. However,
      ZMT-treated mice showed complete recovery of this number. Although Abeta(25-35)
      injection decreased synaptophysin expression in the cerebral cortex and the
      hippocampus, ZMT treatment significantly increased the level of expression of
      synaptophysin up to the control level. Donepezil hydrochloride (DNP, 0.5
      mg/kg/day, p.o.) clinically used for AD had no effect on memory retention and
      synaptophysin levels. Abeta(25-35)-induced neuronal loss was not observed in any
      region of the brain. The present results suggest that memory impairment and
      synaptic loss in AD patients may be improved by treatment with ZMT, even after
      such impairment has already progressed.

PMID- 14568339
TI  - Cytotoxicity of cytokines in cerebral microvascular endothelial cell.
AB  - OBJECTIVE: Several studies reported that the levels of proinflammatory cytokines
      such as TNF-alpha, IL-1beta, IL-6, and IL-8 are elevated in the cerebrospinal
      fluid (CSF) of patients after subarachnoid hemorrhage (SAH). Cytokines in CSF may
      contribute to the development of vasospasm and cerebral ischemia. In the present
      study, we investigated the possible cytotoxic effects of these cytokines on
      cultured cerebral microvascular endothelial cells. METHOD: The effects of TNF
      alpha, IL-1beta, IL-6, and IL-8 were tested using cell viability assay, DNA
      fragmentation analysis (DNA laddering), Western blot analysis (Anti-poly-(ADP
      ribose) polymerase [PARP] antibody), and caspase-3 activity. RESULTS: TNF-alpha
      and IL-1beta, but not IL-6 or IL-8, caused cell detachment in a dose-dependent
      manner (p<0.05). TNF-alpha (200 pg/ml) and IL-1beta (150 pg/ml) produced DNA
      ladders at 24-72 h. TNF-alpha but not IL-1beta cleaved the PARP from 116- to 85
      kDa fragments and enhanced caspase-3 activity at 24-72 h after incubation with
      endothelial cells. Caspase-3 inhibitor at 10 micromol/l significantly prevented
      TNF-alpha-induced cell detachment (p<0.05). DISCUSSION: TNF-alpha induces
      apoptosis in cultured cerebral endothelial cells through the cleavage of caspase
      3. IL-1beta decreases the adherent cells, produces DNA ladders, but fails to
      cleave PARP or increase caspase-3 activity. IL-1beta may induce apoptosis in
      cerebral endothelial cells through different pathway from that of TNF-alpha.

PMID- 14568340
TI  - Role of the prelimbic subregion of the medial prefrontal cortex in acquisition,
      extinction, and reinstatement of cocaine-conditioned place preference.
AB  - Previous research suggests that the prelimbic subregion of the medial prefrontal
      cortex (mPFC) is necessary for acquisition of cocaine-conditioned place
      preference (CPP). Recently, it has been shown that extinguished cocaine-CPP can
      be reinstated by cocaine priming injections, and that this effect reflects the
      incentive motivational effects of the cocaine prime. To determine whether the
      prelimbic cortex is necessary for cocaine-reinstated CPP, rats received bilateral
      infusions of quinolinic acid (lesion group) or vehicle (sham group) into the
      prelimbic cortex and were later tested for acquisition, extinction, and
      reinstatement of cocaine-CPP. Both sham and lesion rats exhibited robust CPP
      established by systemic injections of cocaine (15 mg/kg, i.p.) following either
      one or three drug-environment pairings. Following repeated exposure to the
      cocaine- and saline-paired environments, sham and lesion rats showed similar
      rates of extinction of cocaine-CPP. In contrast, reinstatement of cocaine-CPP by
      cocaine priming injections (5 and 10 mg/kg, i.p.) was attenuated in rats with
      prelimbic cortex lesions relative to sham controls. This finding suggests that
      the prelimbic cortex is involved in the incentive motivational effects of cocaine
      priming.

PMID- 14568341
TI  - Agmatine induces glutamate release and cell death in cultured rat cerebellar
      granule neurons.
AB  - We investigated the effect of agmatine on cell viability of rat cerebellar
      granule neurons in a high-K+ (27.5 mM) medium. Exposure of cultured rat
      cerebellar granule neurons to agmatine (200-800 microM) resulted in a significant
      decrease in cell viability. Agmatine-induced neuronal death began to occur 6-12 h
      after addition, and gradually progressed. The agmatine neurotoxicity was
      attenuated by N-methyl-D-aspartate (NMDA) receptor antagonists and by enzymatic
      degradation of L-glutamate with glutamic pyruvic transaminase. Furthermore, a
      significant increase in extracellular L-glutamate concentration was detected
      before cell death occurred. In addition, agmatine-induced glutamate release and
      cell death were both blocked by pretreatment with botulinum toxin C, which is
      known to specifically inhibit the exocytosis. The agmatine neurotoxicity was not
      observed when extracellular K+ concentration was lower (10 mM). These results
      suggest that agmatine induces glutamate release through the exocytosis and
      thereby causes NMDA receptor-mediated neuronal death in conditions in which
      extracellular K+ concentrations are elevated.

PMID- 14568342
TI  - Age-dependent emergence of oscillatory signal flow between the primary and
      secondary visual cortices in rat brain slices.
AB  - Developmental changes in dynamics of signal propagation between the primary (Oc1)
      and secondary visual cortex (Oc2) were investigated by using optical recording
      methods with voltage-sensitive dyes. Propagating oscillatory optical responses
      were evoked by our previously reported procedure, and were recorded on
      stimulation to white matter of Oc1 in rat visual cortex slices. In immature
      slices, evoked signals spread out from the stimulation site by way of deep
      layers, but were restricted largely to Oc1. In mature slices, however, evoked
      signals spread upward from the stimulation site at first, and then spread out
      along layer II/III, finally to penetrate Oc2. More remarkably, after this initial
      signal was attenuated, oscillatory responses emerged and spread back from Oc2 to
      Oc1 by way of layer II/III, suggesting that the origin of backpropagating
      oscillation is located in Oc2. The initial forward component was dependent on
      both N-methyl-D-aspartate (NMDA) and non-NMDA receptors, and the subsequent
      backward components were dependent only on NMDA receptors. These results suggest
      that the extent of corticocoritcal signal propagation within the visual cortex
      grows wider horizontally during maturation, so that information interchange may
      become easier between the Oc1 and Oc2.

PMID- 14568343
TI  - Pharmacological characterization of lysophospholipid receptor signal transduction
      pathways in rat cerebrocortical astrocytes.
AB  - Lysophosphatidic acid (1-acyl-2-lyso-sn-glycero-3-phosphate; LPA) and sphingosine
      1-phosphate (S1P) are bioactive phospholipids which respectively act as agonists
      for the G-protein-coupled lpA receptors (LPA1, LPA2, and LPA3) and s1p receptors
      (S1P1, S1P2, S1P3, S1P4, and S1P5), collectively referred to as lysophospholipid
      receptors (lpR). Since astrocytes are responsive to LPA and S1P, we examined
      mechanisms of lpR signaling in rat cortical secondary astrocytes. Rat cortical
      astrocyte mRNA expression by quantitative TaqMan polymerase chain reaction (PCR)
      analysis revealed the following order of relative expression of lpR mRNAs:
      s1p3>s1p1>lpa1>s1p2=lpa3>>s1p5. Activation of lpRs by LPA or S1P led to multiple
      pharmacological effects, including the influx of calcium, phosphoinositide (PI)
      hydrolysis, phosphorylation of extracellular receptor regulated kinase (ERK) and
      release of [3H]-arachidonic acid (AA). These signalling events downstream of lpR
      activation were inhibited to varying degrees by pertussis toxin (PTX)
      pretreatment or by the inhibition of sphingosine kinase (SK), a rate-limiting
      enzyme in the biosynthesis of S1P from sphingosine. These results suggest that
      astrocyte lpR signalling mechanisms likely involve both Gi- and Gq-coupled GPCRs
      and that receptor-mediated activation of SK leads to intracellular generation of
      S1P, which in turn amplifies the lpR signalling in a paracrine/autocrine manner.

PMID- 14568344
TI  - Lateral parabrachial lesions impair lithium chloride-induced aversive responses
      but not saccharin-induced flavor preference.
AB  - Behavioral taste-guided experiments, as well as molecular studies employing c-FLI
      expression in response to aversive/appetitive unconditioned stimulus, have
      strongly suggested a visceral role for the lateral parabrachial subnuclei (lPB).
      The main objective in the present study was to further evaluate the functional
      role of the lPB in lithium chloride-induced behavioral/physiological responses.
      We employed a lesion/behavioral experimental strategy combining a lithium
      chloride-induced place aversion procedure together with the simultaneous
      evaluation of behavioral ("Lying on Belly", "LOB") and physiological (body
      temperature) responses elicited by the toxin. Data showed that lPB-lesioned
      animals failed to avoid the chamber previously paired with lithium chloride.
      Moreover, "LOB", and not hypothermia, in response to lithium chloride was
      impaired in parabrachial lesioned animals. Finally, all the animals were tested
      in a free discriminative flavor-preference task induced by saccharin, a non
      caloric reinforcer, which precludes visceral feedback as essential in acquiring
      the learned response. As expected, both control and lesioned animals developed a
      clear flavor-preference to the flavor previously paired with saccharin, which
      shows normal gustatory and associative processing in lPB-lesioned animals. This
      study extends previous results on the functional visceral role of lPB subnuclei
      by providing alternative behavioral evidence other than taste-guided behavior,
      that the lPB is pivotal in visceral processing. Present data are discussed in the
      context of the visceral hypothesis that holds that the lPB is critically involved
      in processing post-oral visceral feedback.

PMID- 14568346
TI  - Stress and amphetamine induce Fos expression in medial prefrontal cortex neurons
      containing glucocorticoid receptors.
AB  - Exposure to stress or amphetamine potently activates the immediate early gene, c
      fos, within medial prefrontal cortex neurons, but the phenotype of these neurons
      is not known. Fluorescence immunohistochemistry was used to determine that a
      large subpopulation of medial prefrontal cortex cells expressing Fos protein
      after restraint and amphetamine also co-express nuclear glucocorticoid receptors
      (GRs). These findings suggest exposure to amphetamine activates the same medial
      prefrontal cortex regions responsible for integration of responses to stress, and
      suggest the potential for AP1-glucocorticoid cross-talk in these cell
      populations.

PMID- 14568345
TI  - Pharmacological characterization of dopamine, norepinephrine and serotonin
      release in the rat prefrontal cortex by neuronal nicotinic acetylcholine receptor
      agonists.
AB  - Neuronal nicotinic acetylcholine receptors (nAChRs) modulate synaptic
      transmission by regulating neurotransmitter release, an action that involves
      multiple nAChRs. The effects of four nAChR agonists, nicotine (NIC), 1,1-dimethyl
      4-phenylpiperzinium iodide (DMPP), cytisine (CYT) and epibatidine (EPI) were
      investigated on [3H]-norepinephrine (NE), [3H]-dopamine (DA) and [3H]-serotonin
      (5-HT) release from rat prefrontal cortical (PFC) slices. All four agonists
      evoked [3H]-DA release to a similar magnitude but with a differing rank order of
      potency of EPI>>DMPP approximately NIC approximately CYT. Similarly, all four
      agonists also increased [3H]-NE release, but with a differing rank order of
      potency of EPI>>CYT approximately DMPP>NIC. NIC-induced [3H]-NE and [3H]-DA
      release responses were both calcium-dependent and attenuated by the sodium
      channel antagonist, tetrodotoxin (TTX) and by the nAChR antagonists mecamylamine
      (MEC) and dihydro-beta-erythroidine (DHbetaE), but not by D-tubocurare (D-TC).
      The modulation of [3H]-5-HT release by nAChR agonists was distinct from that seen
      for catecholamines. DMPP produced robust increases with minimal release observed
      with other agonists. DMPP-induced [3H]-5-HT release was neither sensitive to
      known nAChR antagonists nor dependent on external calcium. The differences
      between nicotinic agonist induced catecholamine and serotonin release suggest
      involvement of distinct nAChRs.

PMID- 14568347
TI  - Immunohistochemical study on the distribution of MnSOD in the central nervous
      system of the transgenic mice expressing a human Cu/Zn SOD mutation.
AB  - In the present study, we used the SOD1(G93A) mutant transgenic mice as an animal
      model of amyotrophic lateral sclerosis (ALS) and performed immunohistochemical
      studies to investigate the changes of MnSOD in the central nervous system of
      transgenic mice at the age of 8, 13, and 18 weeks. In the spinal cord of wild
      type SOD1 (wtSOD1) and SOD1(G93A) transgenic mice, MnSOD-immunoreactive neurons
      were distributed mainly in the anterior horn, although they were also observed in
      the posterior horn. The staining intensity of MnSOD was significantly increased
      in the spinal cord of SOD1(G93A) transgenic mice at presymptomatic and
      symptomatic stage. In the brainstem of symptomatic SOD1(G93A) transgenic mice,
      significantly increased immunoreactivity for MnSOD was observed in abducens
      nucleus, facial nucleus, dorsal motor nucleus of vagus, hypoglossal nucleus,
      medullary and pontine reticular formation, superior and inferior olivary nucleus,
      and cochlear nucleus. The present study provides the first evidence that MnSOD
      immunoreactivity was increased in the central nervous system of SOD(G93A)
      transgenic mice, suggesting that mitochondria may play an important role in the
      pathogenesis and progress of ALS. The mechanisms underlying the increased
      immunoreactivity for MnSOD, and the functional implications of these increases,
      require elucidation.

PMID- 14568348
TI  - Changes in chloride homeostasis-regulating gene expressions in the rat
      hippocampus following amygdala kindling.
AB  - In a rat kindling model, we examined expression patterns of NKCC1, KCC1, KCC2,
      and CLC-2. In the dentate granule cell layer, there was an activity-dependent
      increase in NKCC1 mRNA but significant decreases in KCC1 and CLC-2 mRNAs. In
      addition, CLC-2 mRNA expression was markedly decreased in CA1 pyramidal layer.
      These results suggest that an increase in [Cl-]i and a resultant reduction in
      GABAergic inhibition may occur in hippocampus of epileptic rats.

PMID- 14568349
TI  - Decreased L5 spinal nerve ligation nociceptive behavior following L4 spinal nerve
      transection.
AB  - This study used the escape/avoidance paradigm to explore the role of the L4
      spinal nerve in L5 ligation nociception. Unlike L5-ligated controls, L5
      ligated/L4-transected animals had normal mechanical withdrawal threshold and did
      not escape/avoid mechanical stimulation of the afflicted paw. The result from the
      escape/avoidance paradigm, which does not rely on a reflexive withdrawal
      response, directly supports the hypothesis that the L4 spinal nerve contributes
      to L5 ligation neuropathic pain.

PMID- 14568350
TI  - Ontogeny of circadian clock gene expression in the pineal and the suprachiasmatic
      nucleus of chick embryo.
AB  - Avian circadian rhythms are regulated by a multiple oscillatory system consisting
      of the pineal, the suprachiasmatic nucleus (SCN) and the eye. In the present
      study, ontogeny of circadian clock in the pineal and the SCN of chick embryo was
      examined using Per2 expression as a marker. A daily rhythmicity of Per2
      expression was first detectable at embryonic day (ED) 18 in the pineal and at ED
      16 in the SCN under light-dark (LD) cycles. The amplitude of the rhythmicity
      increased during the development. In contrast, little expression was observed
      during the development in constant darkness. These results suggest that although
      circadian clock matures by the end of the embryonic life in chicken, LD cycles
      are required for the expression of the Per2.

PMID- 14568351
TI  - Fish tolerance to organophosphate-induced oxidative stress is dependent on the
      glutathione metabolism and enhanced by N-acetylcysteine.
AB  - Dichlorvos (2,2-dichlorovinyl dimethyl phosphate, DDVP) is an organophosphorus
      (OP) insecticide and acaricide extensively used to treat external parasitic
      infections of farmed fish. In previous studies we have demonstrated the
      importance of the glutathione (GSH) metabolism in the resistance of the European
      eel (Anguilla anguilla L.) to thiocarbamate herbicides. The present work studied
      the effects of the antioxidant and glutathione pro-drug N-acetyl-L-cysteine (NAC)
      on the survival of a natural population of A. anguilla exposed to a lethal
      concentration of dichlorvos, focusing on the glutathione metabolism and the
      enzyme activities of acetylcholinesterase (AChE) and caspase-3 as biomarkers of
      neurotoxicity and induction of apoptosis, respectively. Fish pre-treated with NAC
      (1 mmol kg(-1), i.p.) and exposed to 1.5 mg l(-1) (the 96-h LC85) of dichlorvos
      for 96 h in a static-renewal system achieved an increase of the GSH content,
      GSH/GSSG ratio, hepatic glutathione reductase (GR), glutathione S-transferase
      (GST), glutamate:cysteine ligase (GCL), and gamma-glutamyl transferase (gammaGT)
      activities, which ameliorated the glutathione loss and oxidation, and enzyme
      inactivation, caused by the OP pesticide. Although NAC-treated fish presented a
      higher survival and were two-fold less likely to die within the study period of
      96 h, Cox proportional hazard models showed that hepatic GSH/GSSG ratio was the
      best explanatory variable related to survival. Hence, tolerance to a lethal
      concentration of dichlorvos can be explained by the individual capacity to
      maintain and improve the hepatic glutathione redox status. Impairment of the
      GSH/GSSG ratio can lead to excessive oxidative stress and inhibition of caspase-3
      like activity, inducing cell death by necrosis, and, ultimately, resulting in the
      death of the organism. We therefore propose a reconsideration of the individual
      effective dose or individual tolerance concept postulated by Gaddum 50 years ago
      for the log-normal dose-response relationship. In addition, as NAC increased the
      tolerance to dichlorvos, it could be a potential antidote for OP poisoning,
      complementary to current treatments.

PMID- 14568352
TI  - DNA integrity determination in marine invertebrates by Fast Micromethod.
AB  - This study was focused toward the adaptation of the previously developed Fast
      Micromethod for DNA damage determination to marine invertebrates for the
      establishment of biomonitoring assessment. The Fast Micromethod detects DNA
      damage (strand breaks, alkali-labile sites and incomplete excision repair) and
      determines DNA integrity in cell suspensions or tissue homogenates in single
      microplates. The procedure is based on the ability of the specific fluorochrome
      dye PicoGreen to preferentially interact with high integrity DNA molecules,
      dsDNA, in the presence of ssDNA and proteins in high alkaline medium, thereby
      allowing direct fluorometric measurements of dsDNA denaturation without sample
      handling and stepwise DNA separations. The results presented herein describe the
      influence of the DNA amount and the pH of the denaturation media on slopes of the
      kinetic denaturation curves and calculated strand scission factors (SSFs). The
      optimal amount of DNA in Mytilus galloprovincialis gills homogenate was found to
      be 100 ng ml(-1) and the greatest differences in DNA unwinding kinetics (slopes
      and SSF values) were reached at pH 11.5. The induction of DNA damage and loss of
      DNA integrity was measured in native DNA isolated from cotton-spinner Holothuria
      tubulosa, marine sponge Suberites domuncula cells and mussel M. galloprovincialis
      gills homogenate. DNA damage and loss of DNA integrity were detected after
      induction by different doses of (gamma-rays, generated by 137Cs 1800 Ci; 0-500
      rad in marine sponge S. domuncula cells up to SSFx(-1) values 0.082 +/- 0.012 for
      the highest radiation dose). Analysis by chemical xenobiotics based on the in
      vitro action of bleomycin (bleomycin-Fe(II) complex 0-50 or 0-83 microg ml(-1)
      (microM)) with native DNA from cotton-spinner H. tubulosa and mussel M.
      galloprovincialis gills homogenate yielded values of 0.537 +/- 0.072 and 0.130 +/
      0.018, respectively. In vivo experiments with mussel M. galloprovincialis gills
      homogenate by 4-nitroquinoline-N-oxide (NQO; 0-1 microg g(-1) NQO mussel) and
      benzo[a]pyrene (B[a]P; 0-20 microg g(-1) B[a]P mussel) indicated SSFx(-1) values
      of 0.121 +/- 0.016 and 0.090 +/- 0.007, respectively, for the highest applied
      doses of chemical xenobiotics. The analytical technique described here allows
      simple and fast analysis of DNA integrity, requires very short time for multiple
      analyses (less than 3 h) and even less than 100 ng DNA per single well (50 ng DNA
      isolated from cotton-spinner, 12,500 sponge cells or about 10 mg of mussel gills
      homogenate) in a microplate. This makes the Fast Micromethod applicable for the
      measurement of DNA integrity of small samples for genotoxicity assessment
      (biomonitoring), the effects of genotoxins on lower marine taxa or sessile
      invertebrates in marine environment (e.g. sponges, mussels) and the estimation of
      directional changes and harmful effects in the ecosystem.

PMID- 14568353
TI  - Antioxidant defenses in killifish (Fundulus heteroclitus) exposed to contaminated
      sediments and model prooxidants: short-term and heritable responses.
AB  - A population of killifish (Fundulus heteroclitus) inhabiting a Superfund site on
      the Elizabeth River (VA, USA) is tolerant of the acute toxicity of the sediments
      from the site; previous work suggests that this tolerance is based both on
      genetic adaptation and physiological acclimation. In this study, larval first-
      and second-generation (F1 and F2) offspring of Elizabeth River killifish were
      more resistant to the toxicity of t-butyl hydroperoxide (a model prooxidant) than
      were King's Creek (reference site) offspring, indicating a heritable tolerance of
      exposure to oxidative stress. In laboratory experiments designed to elucidate the
      mechanistic basis for this increased tolerance, we exposed laboratory-raised F1
      and F2 offspring from Elizabeth River and King's Creek killifish to Elizabeth
      River sediments, menadione, or t-butyl hydroperoxide, and measured the following
      antioxidant parameters: total oxyradical scavenging capacity (TOSC); glutathione
      content (total and disulfide); activities of glutathione reductase (GR);
      glutathione peroxidase (GPx); and glutamate cysteine ligase (GCL) activities and
      protein levels of copper-zinc superoxide dismutase (CuZnSOD); and protein levels
      of manganese superoxide dismutase (MnSOD). Exposure to Elizabeth River sediments
      lead to consistent increases in total glutathione concentrations, GR activities,
      and MnSOD protein levels, and in some cases increased GPx and GCL activities, in
      both populations. In addition, Elizabeth River offspring (larvae) showed higher
      basal TOSC values, glutathione concentrations, and MnSOD protein levels. These
      data suggest that upregulated antioxidant defenses play a role in both short-term
      (physiological) and heritable (multigenerational/evolutionary) tolerance of the
      toxicity of these Superfund sediments. The responses of specific antioxidant
      parameters, including sex-specific responses in the cases of glutathione
      concentrations and GR activity, are also discussed.

PMID- 14568354
TI  - Gonad development and vitellogenin production in zebrafish (Danio rerio) exposed
      to ethinylestradiol and methyltestosterone.
AB  - In a partial life-cycle test, the impact of 17alpha-ethinylestradiol (EE2) and
      17alpha-methyltestosterone (MT) on juvenile zebrafish was evaluated by use of
      vitellogenin measurements and gonadal development. Exposure to EE2 (1-25 ng/l)
      resulted in a dose-dependent increase in vitellogenin production starting at 2
      ng/l. Significant changes in sex ratios in female direction were detected at 1
      ng/l, with complete sex reversal taking place after exposure to 2 ng/l. No
      intersex fish were observed after exposure to EE2. Exposure to MT resulted in
      decreased vitellogenin concentrations. Complete sex reversal was detected in all
      MT concentrations used (26-1000 ng/l). A large proportion of intersex fish was
      observed after exposure to 1000 ng MT/l. The period of gonadal sex reversal in
      non-exposed zebrafish was also studied. The main morphological features of the
      transformation of ovaries into testis were observed 4-5 weeks after hatching.

PMID- 14568355
TI  - Differential metallothionein induction patterns in three freshwater fish during
      sublethal copper exposure.
AB  - We assessed whether fish that tolerate higher levels of Cu exposure have a higher
      capacity to induce metallothionein (MT) synthesis than other, more sensitive,
      fish species. Furthermore, we examined if a correlation could be found between
      tissue Cu accumulation and MT levels. Cu accumulation and MT concentrations in
      gill, liver, kidney and muscle of rainbow trout (Oncorhynchus mykiss), common
      carp (Cyprinus carpio) and gibel carp (Carassius auratus gibelio) were measured
      during a 1 week exposure to a sublethal Cu (1 microM). Different patterns were
      observed for the three species regarding Cu accumulation as well as MT induction.
      Virtually no Cu accumulation was seen in rainbow trout gill, while in both
      cyprinid species gill Cu levels increased three- to four-fold. Cu accumulated
      fast in common carp (within the first day), but slow in gibel carp (1 week). Gill
      MT induction was obvious in gibel carp only, with an increase of 156% after 1
      week of exposure. Liver accumulated most Cu in rainbow trout (235% increase) and
      common carp (144% increase), with Cu levels in liver being significantly higher
      in rainbow trout compared to the carp species from the start. MT induction was
      pronounced in common carp liver only (138% increase). In gibel carp liver, there
      was no clear Cu accumulation or MT induction. In contrast, gibel carp was the
      only species to show Cu accumulation in kidney after 3 days of exposure (83%
      increase), after which levels returned to normal. Concomitantly, gibel carp
      kidney was also the only kidney tissue to show MT induction (192-195% increase
      after 3 and 7 days). In common carp, a significant decrease of kidney MT levels
      was observed from day 1 onwards. In muscle, Cu accumulation was clear for the two
      cyprinid species (three- to four-fold increase) but not for rainbow trout. Of the
      species studied, gibel carp is the most resistant to copper polluted
      environments, and showed a positive significant relationship between tissue
      copper concentrations and MT levels in gill, liver and muscle tissues. Common
      carp showed an intermediate response, with significant correlations in liver and
      muscle tissue. In contrast, we found low MT induction in rainbow trout, the most
      sensitive species, and no correlation at all between MT concentrations and tissue
      copper contents. Possibly, the regulatory capacity for copper homeostasis was
      exceeded in rainbow trout, and MT synthesis inhibited.

PMID- 14568356
TI  - Adverse effects of (surface water pollutants) Cd, Cr and Pb on the embryogenesis
      of the mallard.
AB  - The effects of chromium, lead and cadmium were studied on the embryogenesis,
      hatching success and viability of the mallard. Eggs were exposed to relatively
      low environmental concentrations that are characteristic to the level in polluted
      Hungarian surface waters. Eggs were treated by injection or immersion--prior to
      incubation. In study I, effects on early embryogenesis (first 10 days of
      incubation) were examined. Eggs were opened daily, mortality was determined and
      permanent slides of the embryos were made to help further external examinations.
      Each metal proved to be toxic to the developing mallard embryo, causing an
      increase in mortality and developmental anomalies. Chromium was the most
      teratogenic of the three heavy metals increasing the rate of malformations by 30%
      (P<0.001) after immersion, and 17% (P<0.01) after injection of the eggs. Cadmium
      proved to cause the highest rate of mortality. Embryonic death was increased by
      27% (P<0.01) and 40% (P<0.001) after Cd immersion and injection, respectively. In
      study II, effects on hatching and viability of the ducklings were studied. The
      eggs were hatched, hatching and mortality rates were established, the liver of
      animals was histopathologically examined. However each heavy metal decreased
      hatching success, cadmium was found the most toxic compound, causing a 21%
      (P<0.01) and 47% (P<0.001) reduction in hatching success after immersion and
      injection, respectively. The liver of hatched ducklings showed significant
      lesions, dystrophy in the form of hepatic necrosis was detected in each treated
      animal. Each heavy metal (Cr, Pb, Cd) proved to have adverse effects on the
      embryonic development, hatching and viability of the mallard.

PMID- 14568357
TI  - Behavioural response of the cladoceran Daphnia magna STRAUS to sublethal Copper
      stress--validation by image analysis.
AB  - In this study changes in the locomotory behaviour of the freshwater cladoceran
      Daphnia magna STRAUS were used as sublethal indicators of toxic copper (Cu)
      stress. The behavioural responses were determined by a real time image analysis,
      using a video camera and a Pentium-PC equipped with a standard low cost frame
      grabber. For a sequence of 50 images per group, where 10 daphnids were moving
      simultaneously, the trajectories have been reconstructed in binary image
      sequences. As biological endpoints, we defined the average swimming velocity and
      the average duration of swimming activity and inactivity. The behavioural
      responses of the daphnids were analysed under normal conditions (without Cu
      stress) and after application of sublethal Cu stress of following concentrations
      (in microg l(-1) (ppb)): C1=1, C2=5, C3=10, C4=20, C5=30. The test organisms were
      exposed to the Cu concentration for 24 h under static conditions. Already after 9
      h of Cu-exposure a significant (*P<0.05) decrease of the average swimming
      velocity could be observed at the group of the highest Cu concentration (30 ppb).
      After 13 h of Cu-contamination the swimming velocity was significantly (*P<0.05)
      reduced at group of 20 ppb Cu-treatment and after 14 h a significant (*P<0.05)
      decrease of the average swimming velocity could be measured at the group of 10
      ppb Cu-treatment. No significant decrease of the swimming velocity could be
      observed in the 1 and 5 ppb Cu-treatment.

PMID- 14568358
TI  - Inducibility of the P-glycoprotein transport activity in the marine mussel
      Mytilus galloprovincialis and the freshwater mussel Dreissena polymorpha.
AB  - Previous investigations directed to the determination of the P-glycoprotein (Pgp)
      expression in aquatic organisms have indicated the possibility of the
      multixenobiotic resistance mechanism (MXR) induction as a response to organic
      pollution. However, in numerous cases no significant and/or no clear relationship
      between Pgp contents and pollution level was detected. Concerning these
      discrepancies the results of an extensive, 3-year study of the Pgp mediated MXR
      induction in the selected freshwater (Dreissena polymorpha) and marine (Mytilus
      galloprovincialis) bivalves are presented here. The main goals of the study were
      to ascertain the rate-dynamic, level, as well as the possible usability of MXR in
      environmental biomonitoring. Since the primary result of MXR induction should be
      the decreased intracellular accumulation of xenobiotics, the determination of MXR
      induction was performed using the measurement of Pgp transport activity. We
      measured the accumulation or the efflux rate of the model Pgp substrate rhodamine
      B (RB) in gills of the mussels previously exposed to pollution. The study was
      performed in several steps: from the exposure experiments in laboratory, using
      model inducers rhodamine 123 (R123) and water extract of Diesel-2 oil (D2), to
      the final in situ testing in real environmental conditions. Our results confirmed
      that Pgp activity is induced/induces according to the level of pollution, and
      that 4-days period was already long enough for the significant induction and
      deinduction of MXR activity. However, the inducibility of Pgp transport activity
      was significantly limited--the maximal level of induction obtained in this study
      resulted in 50-60% lower RB accumulation in the gills of induced specimens
      (laboratory or in situ exposed to pollution), when compared to control, non
      induced animals. The obtained level of Pgp related MXR induction, resulting in
      halfway lesser accumulation of a model pollutant (RB), extrapolated to the
      similar scenario with toxic xenobiotics may have significant environmental
      relevance. However, our results also suggest that for the use of the MXR as a
      relevant biomarker the Pgp transport activity should be measured along with the
      determination of DNA, mRNA or/and protein expression. Based on the data from this
      study several factors that may have had critical influence on the effectiveness
      and the level of MXR induction are additionally discussed.

PMID- 14568359
TI  - Insulin-like growth factor-1 and post-ischemic brain injury.
AB  - Insulin-like growth factor-1 (IGF-1) is a naturally occurring neurotrophic factor
      that plays an important role in promoting cell proliferation and differentiation
      during normal brain development and maturation. The present review examines
      recent evidence that endogenous IGF-1 also plays a significant role in recovery
      from insults such as hypoxia-ischemia and that giving additional exogenous IGF-1
      can actively ameliorate damage. It is now well established that neurons and other
      cell types die many hours or even days after initial injury due to activation of
      programmed cell death pathways. IGF-1 and its binding proteins and receptors are
      intensely induced within damaged brain regions following brain injury, suggesting
      a possible a role for IGF-1 in brain recovery. Exogenous administration of IGF-1
      within a few hours after brain injury is now known to be protective in both gray
      and white matter and leads to improved somatic function. In contrast, pre
      treatment is ineffective, likely reflecting limited intracerebral penetration of
      IGF-1 into the uninjured brain. The neuroprotective effects of IGF-1 are mediated
      by IGF-1 receptors and its binding proteins and are specific to particular
      cellular phenotypes and brain regions. The window of opportunity for treatment
      with IGF-1 is limited to a few hours after normothermic brain injury, reflecting
      its specific actions on early, intracellular events in the apoptotic cascade.
      However, injury-associated mild post-hypoxic hypothermia, which delays the
      development of cell death, can shift and dramatically extend the window of
      opportunity for delayed treatment with IGF-1. Such a combined approach is likely
      to be essential for any clinical treatment.

PMID- 14568360
TI  - Yin and Yang: complement activation and regulation in Alzheimer's disease.
AB  - The spectrum of inflammatory diseases is nowadays considered to include diverse
      diseases of the central nervous system (CNS). Current evidence suggests that
      syndromes such as Alzheimer's disease (AD) have important inflammatory and immune
      components and may be amenable to treatment by anti-inflammatory and
      immunotherapeutic approaches. Compelling evidence has been reported that
      complement activation occurs in the brain with Alzheimer's disease, and that this
      contributes to the development of a local inflammatory state that is correlated
      with cognitive dysfunction. The complement system is a critical element of the
      innate immune system recognizing and killing, or targeting for destruction,
      otherwise pathogenic organisms. In addition to triggering the generation of a
      membranolytic complex, complement proteins interact with cell surface receptors
      to promote a local inflammatory response that contributes to the protection and
      healing of the host. Complement activation causes inflammation and cell damage,
      yet it is an essential component in trying to eliminate cell debris and
      potentially toxic protein aggregates. It is the balance of these seemingly
      competing events--the "Yin" and the "Yang"--that influences the ultimate state of
      neuronal function. Knowledge of the unique molecular interactions that occur in
      the development of Alzheimer's disease, the functional consequences of those
      interactions, and the proportional contribution of each element to this disorder,
      should facilitate the design of effective therapeutic strategies for this
      disease.

PMID- 14568361
TI  - Patterned Purkinje cell death in the cerebellum.
AB  - The object of this review is to assemble much of the literature concerning
      Purkinje cell death in cerebellar pathology and to relate this to what is now
      known about the complex topography of the cerebellar cortex. A brief introduction
      to Purkinje cells, and their regionalization is provided, and then the data on
      Purkinje cell death in mouse models and, where appropriate, their human
      counterparts, have been arranged according to several broad categories--naturally
      occurring and targeted mutations leading to Purkinje cell death, Purkinje cell
      death due to toxins, Purkinje cell death in ischemia, Purkinje cell death in
      infection and in inherited disorders, etc. The data reveal that cerebellar
      Purkinje cell death is much more topographically complex than is usually
      appreciated.

PMID- 14568362
TI  - Home care for terminally ill Turks and Moroccans and their families in the
      Netherlands: carers' experiences and factors influencing ease of access and use
      of services.
AB  - The aim of this study was to explore the experiences of relatives of elderly
      terminally ill Turks and Moroccans regarding Dutch professional home care and the
      barriers to the use this care. Nine Turkish and ten Moroccan family members, who
      recently looked after dying members of their families, were interviewed using a
      semi-structured topic list. The data was analyzed using the method described by
      Glaser and Strauss. The results of this study make it clear that there is no
      uniform pattern in the use of home care. However, family members who did use home
      care facilities were all satisfied. Furthermore, on the basis of this study,
      several factors influencing access to and use of home care were discerned, e.g.,
      illness, family structure, decision making, pressure from the community,
      information and formal referrals. In addition, the authors found that
      'preferences regarding family care' influenced all former factors.

PMID- 14568363
TI  - Investigation of factors influencing burnout levels in the professional and
      private lives of nurses.
AB  - This is a descriptive, cross-sectional and partly analytic study aiming to
      determine the factors causing burnout in professional and private lives of nurses
      working in the university and state hospitals in a city. About 333 nurses were
      reached by sampling method. Data collection was made by a question form
      consisting of two parts. The first part was developed by the investigators. In
      this part, data on demographic, professional and private life conditions of
      individuals were collected. In the second part, "Maslach Burnout Inventory" was
      used to determine the burnout levels of individuals. The most important findings
      of the present study are as follows: higher education level, work experience and
      higher status decrease burnout while working at night shifts increases it. In
      addition, nurses who have problems in relations with the other team members and
      are not satisfied with their work conditions have higher levels of burnout.
      Having difficulty in childcare and in doing house chores, health problems of the
      nurse herself or her children, economic hardships and difficulties encountered in
      transportation are other factors increasing burnout.

PMID- 14568364
TI  - Inquiry-based learning: facilitators' perceptions of their effectiveness in the
      tutorial process.
AB  - This preliminary study evaluates the effectiveness of facilitators in the inquiry
      based learning tutorial process and identifies areas for staff development. Self
      report checklists measure the key dimensions and role of the facilitator in four
      tutorial process steps: Exploration, Review, Consolidation and Plenary. The
      population study comprised 43 potential respondent facilitators in the pre
      registration nursing programme. The response rate was 55% (N=23). Descriptive and
      non-parametric measures were used to analyse the data. Findings indicated that
      the overall majority of facilitators perceive the effectiveness of their role to
      be satisfactory. Differences in the results were found when compared by length of
      experience.

PMID- 14568365
TI  - Constipation and the preached trio: diet, fluid intake, exercise.
AB  - A survey of 90 older community-dwelling people's constipation experience is
      reported in part. The focus is the participants' efforts to use diet, fluid
      intake and exercise as preventive strategies. Most feel that they have been
      preached to in this regard. However, constraints may prevent full adherence to
      the trio and although some have gained from diet adjustment, the majority is
      disillusioned about these strategies. Nurses should be aware that scientific and
      medical literature is discussing evidence that dietary fibre intake preventing
      constipation is not proven, that fluid intake does not necessarily determine
      stool bulk or speed colon transit time, and that there is no proven link between
      exercise levels and chronic constipation.

PMID- 14568366
TI  - The New Zealand development and trial of mental health nursing clinical
      indicators--a bicultural study.
AB  - This paper describes the development and validation of bicultural clinical
      indicators that measure achievement of mental health nursing practice standards
      in New Zealand (ANZMCHN, 1995, Standards of practice for mental health nursing in
      New Zealand. ANZCMHN, Greenacres). A four-stage research design was utilised
      including focus groups, Delphi surveys, a pilot, and a national field study, with
      mental health nurses and consumers as participants. During the national field
      study, consumer files (n=327) from 11 District Health Boards, and registered
      nurses (n=422) completed an attitude questionnaire regarding the regularity of
      specific nursing and service activities. Results revealed a variation in the mean
      occurrence of the clinical indicators in consumer case notes of 18.5-89.9%. Five
      factors with good internal consistency, encompassing domains of mental health
      nursing required for best practice, were derived from analysis of the
      questionnaire. This study presents a research framework for developing culturally
      and clinically valid, reliable measures of clinical practice.

PMID- 14568367
TI  - Development of an instrument to measure the responses and management of Chinese
      primary caregivers in caring of children with minor upper respiratory disorders.
AB  - This article focuses on the development of a valid, reliable and culturally
      sensitive instrument to assess the responses and management of Chinese primary
      caregivers caring for children aged below 10 with minor upper respiratory
      disorders. Thirty-two semi-structured interviews were conducted as the point of
      saturation of qualitative data was reached. The qualitative findings contributed
      to the development of the instrument items. Five main categories and 29 sub
      categories were identified with satisfactory inter-coder reliability. A panel of
      three experts judged the content validity of the instrument with a content
      validity index of 0.98. A test-retest procedure with 40 subjects was adopted and
      the correlation coefficient for the instrument was 0.850 (p< or =0.000).

PMID- 14568368
TI  - The effects of home-based pulmonary rehabilitation in patients with chronic lung
      disease.
AB  - The purpose of this study was to examine the effects of a home-based pulmonary
      rehabilitation program on lung function, dyspnea, exercise tolerance, and quality
      of life in 23 Koreans with moderate to severe chronic lung disease. The outcome
      measures were forced expiratory volume in 1s (FEV1, % predicted), Borg score, 6
      min walking distance (6MWD), and chronic respiratory disease questionnaire
      (CRDQ). Experimental group (n=15) performed the 8-week home-based pulmonary
      rehabilitation program, composed of inspiratory muscle training, upper and lower
      extremity exercise, relaxation, and telephone visit. Patients in control group
      (n=8) were only given educational advice. The experimental group showed a lower
      level of exertional dyspnea, more exercise tolerance, and greater improvement in
      health-related quality of life than the control group (p<0.05). Lung function was
      not statistically different. This study yielded evidence for the beneficial
      effects of home-based pulmonary rehabilitation program.

PMID- 14568369
TI  - Decision-making in palliative and continuing care in the community: an analysis
      of the published literature with reference to the context of UK care provision.
AB  - Palliative and continuing care in the United Kingdom (UK) is provided by a range
      of health and social care professionals who work within a variety of statutory
      and non-statutory organisations. This selective review of the literature focuses
      upon palliative and continuing care decision-making undertaken by district nurses
      and social workers as an exemplar of interprofessional decision-making. The
      decision-making process is complex and heavily influenced by the organisations
      employing district nurses and social workers. A model of strategic decision
      making is identified which facilitates the exploration of events within the
      context of practice, thus providing a greater understanding of the process and
      outcomes to inform the professional development of practitioners.

PMID- 14568370
TI  - Describing chronic pain: towards bilingual practice.
AB  - This paper reports on the findings of a pilot study that collated and categorised
      a range of Welsh-medium chronic pain descriptors and their conceptually
      equivalent English translations in order to provide a preliminary basis for
      chronic pain assessment amongst patients in the bilingual community of North West
      Wales. The results demonstrate the unique and complex nature of individual pain
      experiences and the challenges of meaningful interpretation, particularly when
      patient and practitioner do not share a common preferred language. Detailed
      analysis of the descriptors provided valuable insight into the patient's world,
      revealing cultural patterns of beliefs and behaviours as well as the suffering
      associated with chronic pain. Implications for improving chronic pain assessment
      amongst bilingual speakers are explored.

PMID- 14568371
TI  - Survivors and victims of hospital restructuring and downsizing: who are the real
      victims?
AB  - This study reports the results of a longitudinal study of the effects of hospital
      restructuring and downsizing on nursing staff satisfaction and psychological well
      being. Participants completed questionnaires in November 1996 and November 1999.
      All were employed as hospital-based nurses in 1996 but some had left hospital
      nursing for other jobs by 1999. Nurses still employed in hospital settings
      (N=744) were compared with nurses now employed elsewhere (N=74). Hospital-based
      nursing staff reported less job satisfaction, more absenteeism, greater
      psychological burnout and poorer psychological well-being than nurses now
      employed elsewhere.

PMID- 14568373
TI  - A decay of gap junctions associated with ganglion cell differentiation during
      retinal regeneration of the adult newt.
AB  - Changes in the gap junctional coupling and maturation of voltage-activated Na(+)
      currents during regeneration of newt retinas were examined by whole-cell patch
      clamping in slice preparations. Progenitor cells in regenerating retinas did not
      exhibit Na(+) currents but showed prominent electrical and tracer couplings.
      Cells identified by LY-fills were typically slender. Na(+) currents were detected
      in premature ganglion cells with round somata in the 'intermediate-II'
      regenerating retina. No electrical and tracer couplings were observed between
      these cells. Mature ganglion cells did not exhibit electrical coupling, but
      showed tracer coupling. On average, the maximum Na(+) current amplitude recorded
      from premature ganglion cells was roughly 2.5-fold smaller than that of mature
      ganglion cells. In addition, the activation threshold of the Na(+) current was
      nearly 11 mV more positive than that of mature cells. We provide morphological
      and physiological evidence showing that loss of gap junctions between progenitor
      cells is associated with ganglion cell differentiation during retinal
      regeneration and that new gap junctions are recreated between mature ganglion
      cells. Also we provide evidence suggesting that the loss of gap junctions
      correlates with the appearance of voltage-activated Na(+) currents in ganglion
      cells.

PMID- 14568374
TI  - Spatial and temporal tuning of motion in depth.
AB  - We used the Pulfrich effect to investigate perception of motion in depth.
      Independent manipulation of spatial and temporal frequency content in
      stereoscopic motion stimuli revealed the tuning characteristics of motion-in
      depth perception. Sensitivity to interocular phase difference between
      sinusoidally oscillating sine-wave gratings was measured in four observers who
      judged direction of motion in depth. Discrimination thresholds in terms of
      interocular phase difference were determined to investigate spatial and temporal
      tuning characteristics of a system that is based on interocular phase difference,
      interocular delay, binocular disparity and velocity difference. Temporal
      frequency tuning of interocular phase difference thresholds was band pass and
      relatively dependent on spatial frequency variation. These results together with
      evidence from two control experiments support the idea that sensitivity to
      direction of motion in depth is limited by a stereo-motion system that monitors
      binocular horizontal disparity and motion rather than interocular phase
      difference, interocular delay, or interocular velocity difference.

PMID- 14568375
TI  - Spatial summation of S-cone ON and OFF signals: effects of retinal eccentricity.
AB  - We studied spatial summation for S-cone ON and OFF signals as a function of
      retinal eccentricity in human subjects. S-cone isolation was obtained by the two
      colour threshold method of Stiles, modified by adding blue light to the yellow
      background. Test stimuli were blue light increments or decrements within a
      circular area of variable size. These were presented for 100 ms at 0 to 20 deg
      along the horizontal temporal retinal meridian. Ricco's area of complete spatial
      summation was measured from the threshold vs. area curves. This was nearly
      constant and approximately the same for both types of stimuli within the 0-5 deg
      range and increased beyond this range. The decremental area increased faster,
      suggesting that separate mechanisms, presumably ON and OFF, integrate S-cone
      increments and decrements. The results appear to provide new evidence for the
      existence of separate S-cone ON and OFF pathways. We compare the data with known
      morphology of primate retina and assume that, if S-cone decrements are detected
      via separate OFF cells, these should differ in density and dendritic field size
      from the S-cone ON cells, but only in the retinal periphery.

PMID- 14568376
TI  - Colour and luminance selectivity of spatial and temporal interactions in
      orientation perception.
AB  - Previous studies have commented upon the similar phenomenology of simultaneous
      and successive interactions in the perception of orientation. These similarities
      have been taken as evidence of common mechanisms underlying the simultaneous tilt
      illusion (TI) and the successive tilt aftereffect (TAE). We measured the TI and
      TAE for four subjects for combinations of test and inducing stimuli modulated
      along either the same or orthogonal axes of colour space within the L+M+S, L-M
      colour-luminance plane. The largest TI and TAE were found when test and inducer
      were modulated along the same axis of colour space. The TI consistently showed
      greater selectivity for colour/luminance than the TAE. The results are discussed
      in relation to the known chromatic properties of the primate visual pathways.
      Specifically, we suggest that both the TI and TAE involve colour- and luminance
      specific neurons in primary visual cortex as well as cue-invariant mechanisms in
      extrastriate cortex.

PMID- 14568377
TI  - The shape and size of crowding for moving targets.
AB  - Our ability to identify alphanumeric characters can be impaired by the presence
      of nearby features, especially when the target is presented in the peripheral
      visual field, a phenomenon is known as crowding. We measured the effects of
      motion on acuity and on the spatial extent of crowding. In line with many
      previous studies, acuity decreased and crowding increased with eccentricity.
      Acuity also decreased for moving targets, but the absolute size of crowding zones
      remained relatively invariant of speed at each eccentricity. The two-dimensional
      shape of crowding zones was measured with a single flanking element on each side
      of the target. Crowding zones were elongated radially about central vision,
      relative to tangential zones, and were also asymmetrical: a more peripheral
      flanking element crowded more effectively than a more foveal one; and a flanking
      element that moved ahead of the target crowded more effectively than one that
      trailed behind it. These results reveal asymmetrical space-time dependent regions
      of visual integration that are radially organised about central vision.

PMID- 14568378
TI  - Effects of light and dark adaptation of rods on specific-hue threshold.
AB  - Specific-hue threshold as a function of absolute rod threshold was measured with
      long-, middle-, and short-wavelength monochromatic test lights presented 17 deg
      extrafoveally. The measurements were obtained both during the rod phase of long
      term dark adaptation and under conditions where the rod receptor system was
      gradually light adapted from a dark-adapted state by a scotopic background field
      of increasing retinal illumination. The results show that change in specific-hue
      threshold with change in absolute rod threshold is not, in general, identical for
      light and dark adaptation of the rod receptor system. Thus, in the long- and
      middle-wavelength test regions, the specific-hue threshold could be obtained at
      higher intensities under the light- as compared to the dark-adaptation condition
      when absolute rod thresholds were the same. Just the opposite was found for the
      short-wavelength tests. It is concluded that change in specific-hue threshold
      with light and dark adaptation of the rod receptor system is not, in general,
      controlled by the same mechanism.

PMID- 14568379
TI  - Collinear contextual suppression.
AB  - The context of a target can modulate behavioral as well as neural responses to
      that target. For example, target processing can be suppressed by iso-oriented
      surrounds whereas it can be facilitated by collinear contextual elements. Here,
      we present experiments in which collinear elements exert strong suppression
      whereas iso-oriented contextual surrounds yield no contextual modulation-
      contrary to most studies in this field. We suggest that contextual suppression
      depends strongly on the spatial arrangement of the context pointing to the
      influence of Gestalt factors in contextual modulation.

PMID- 14568380
TI  - Attentional modulation of threshold sensitivity to first-order motion and second
      order motion patterns.
AB  - Previous studies [e.g. Vision Research 40 (2000) 173] have shown that when
      observers are required to selectively attend to one of two, spatially-adjacent
      patches containing either first-order (luminance-defined) or second-order
      (contrast-defined) motion, threshold sensitivity for identifying the direction of
      second-order motion, but not first-order motion, is enhanced for the attended
      stimuli. The processing of second-order motion, unlike first-order motion, may,
      therefore, require attention. However, other studies have found little evidence
      for differential effects of attention on the processing of first-order and second
      order motion [Investigative Ophthalmology and Visual Science 42(4) (2001) 5061].
      We investigated the effects of attention instructions on the ability of observers
      to identify the directions and spatial orientations of luminance-defined and
      contrast-defined motion stimuli. Pairs of motion stimuli were presented
      simultaneously and threshold performance was measured over a wide range of drift
      temporal frequencies and stimulus durations. We found: (1) direction
      discrimination thresholds for attended motion stimuli were lower than those for
      unattended stimuli for both types of motion. The magnitude of this effect was
      reduced when the observers were not given prior knowledge of which patch of
      motion (attended or unattended) they had to judge first. (2) Direction
      discrimination for first-order motion was similarly affected at all temporal
      frequencies and durations examined, but for second-order motion the effects of
      attention depended critically on the drift temporal frequency and stimulus
      duration used. (3) Orientation discrimination showed little or no influence of
      attention instructions. Thus, whether or not attention influences the processing
      of second-order motion depends crucially on the precise stimulus parameters
      tested. Furthermore under appropriate conditions the processing of first-order
      motion is also influenced by attention, albeit to a lesser extent than second
      order motion.

PMID- 14568381
TI  - Visual reaction time: neural conditions for the equivalence of stimulus area and
      contrast.

PMID- 14568383
TI  - Amplitude dependent accommodative dynamics in humans.
AB  - Dynamics of accommodation (far-to-near focus) and disaccommodation (near-to-far
      focus) are described as a function of response amplitude. Accommodative responses
      to step stimuli of various amplitudes presented in real space were measured in
      eight 20-30 year old subjects. Responses were fitted with exponential functions
      to determine amplitude, time constant and peak velocity. Despite the intersubject
      variability, the results show that time constants of accommodation and peak
      velocity of disaccommodation increase with amplitude in all subjects. The
      dynamics of accommodation and disaccommodation are dependent on amplitude, but
      have different properties in each case.

PMID- 14568384
TI  - The innate immune system of the gastrointestinal tract.

PMID- 14568385
TI  - Lactoferrin--a multifunctional protein with antimicrobial properties.
AB  - Lactoferrin is a member of the transferrin family of iron-binding proteins.
      Numerous functions have been reported and continue to be reported for the
      protein, some of which are related to its iron-binding properties. Its extensive
      antimicrobial activities were originally attributed to its ability to sequester
      essential iron, however, it is now established that it possesses bactericidal
      activities as a result of a direct interaction between the protein or lactoferrin
      derived peptides. This article reviews the antimicrobial activities of
      lactoferrin and discusses the potential mode of action of lactoferrin-derived
      cationic peptides against Gram-negative bacteria in the light of recent studies.

PMID- 14568386
TI  - Electrostatic sensor for identifying interactions between peptides and bacterial
      membranes.
AB  - The use of the membrane probe fluorescein phosphatidylethanolamine (FPE) to
      investigate membrane binding is well established. However, until now, its use has
      been restricted to studies involving peptides and eukaryotic membranes. This
      useful tool has been developed to interrogate peptide:prokaryotic membrane
      interactions by introducing novel methodology to incorporate FPE into the
      membranes of UV killed, whole bacterial cells. The electrostatic potential of the
      membrane in the immediate vicinity of the probe affects the protonation state of
      the xanthene ring system in the fluorescein head group, which is held close to
      the membrane surface. When altered, e.g. by peptide binding and insertion, a
      change in fluorescence results, which can be measured spectrophotometrically.
      Applicability of this technique to bacterial surface interactions was confirmed
      by production of a binding curve for both a synthetic peptide and a 37kDa
      protein. Future investigations are anticipated to utilize this technology to
      characterize interactions of other toxins plus antimicrobial peptides such as
      lactoferricin and defensins with their target membranes.

PMID- 14568387
TI  - Rapid sequence divergence in mammalian beta-defensins by adaptive evolution.
AB  - beta-Defensin genes encode broad spectrum antimicrobial cationic peptides. We
      have analysed the largest murine and human clusters of these genes, which
      localise to mouse and human chromosome 8. Using hidden Markov models, we
      identified novel mouse and human beta-defensin genes. We subsequently found full
      length expressed transcripts for these novel genes. Expression in the mouse was
      high in brain and reproductive tissues. Fourteen murine beta-defensins could be
      grouped into two clear sub-groups by virtue of their position and high signal
      sequence (exon 1 encoded) identity. In contrast, there was a very low level of
      sequence conservation in the exon 2 region encoding the mature antimicrobial
      peptide. Evolutionary analysis revealed strong evidence that following gene
      duplication, exon 1 and surrounding non-coding DNA show little divergence within
      subfamilies. The focus for rapid sequence divergence is localised in the DNA
      encoding the mature peptide and this is driven by accelerated positive selection.
      In the human we also conclude that the locus has evolved by successive rounds of
      duplication followed by substantial divergence involving positive selection, to
      produce a diverse cluster of paralogous genes prior to human-baboon divergence.
      This mechanism of adaptive evolution is consistent with the role of this gene
      family as defence against bacterial pathogens. In order to look at function of
      these rapidly evolving genes, we characterised one of the novel mouse beta
      defensin genes. This gene deviates from the canonical six cysteine motif present
      in the mature functional peptide of all other beta defensins. This defensin
      related gene (Defr1) is most highly expressed in testis and heart and the genomic
      organisation is highly similar to Defb3-6. A synthetic Defr1 peptide was shown to
      exist as a dimer and yet displayed both antimicrobial and chemotactic activity.
      The antimicrobial activity of Defr1 against S. aureus, E. coli and B. cepacia was
      found to be reduced in raised concentration of NaCl, but its action against P.
      aeruginosa was independent of NaCl concentration. These data have major
      implications on the structure and functions of these important host defence
      molecules.

PMID- 14568388
TI  - The role of mannose-binding lectin in health and disease.
AB  - Mannose-binding lectin (MBL) is a pattern recognition molecule of the innate
      immune system. It belongs to the collectin family of proteins in which lectin
      (carbohydrate-recognition) domains are found in association with collagenous
      structures. In man, these proteins include serum MBL, lung surfactant protein A
      (SP-A) and lung surfactant protein D (SP-D). MBL binds to a range of sugars
      including N-acetyl-D-glucosamine, mannose, N-acetyl-mannosamine, fucose and
      glucose. This permits the protein to interact with a wide selection of viruses,
      bacteria, yeasts, fungi and protozoa decorated with such sugars. Unlike the other
      collectins, MBL bound to microbial surfaces is able to activate the complement
      system in an antibody and C1-independent manner. This activation is mediated by
      complexes of MBL with a serine protease called MBL-associated serine protease 2
      (MASP-2), which specifically cleaves C4 and C2 to create a C3 convertase enzyme.
      MBL may also interact directly with cell surface receptors and thereby promote
      opsonophagocytosis by a complement-independent pathway. It has been suggested
      that MBL plays an important role in the first hours/days of any primary immune
      response to a sugar decorated pathogen. This provides the host with a first-line
      of defence before the adaptive immune system becomes operative and in humans may
      be particularly important between 6 and 18 months of age when the adaptive system
      is still immature. MBL deficiency is one of the most common human
      immunodeficiencies and arises primarily from three single point mutations in exon
      1 of the MBL-2 gene. These mutations result in a failure to assemble fully
      functional multimeric protein. Several studies have shown that deficiency of MBL
      increases the overall susceptibility of an individual to infectious disease. The
      most striking example of this is the association of acute respiratory tract
      infections with MBL deficiency in early childhood. In contrast, there is evidence
      that for some intracellular parasites MBL deficiency may be protective and this
      might explain the high frequency of MBL mutations in sub-Saharan Africa and South
      America. Increasingly, there is evidence that the association between MBL levels
      and disease is complex. For example, the protein appears to influence the
      severity of several diseases. The mechanism whereby MBL exerts such effects is
      unclear but one possibility is through a dose-dependent modulation of pro
      inflammatory cytokines.

PMID- 14568389
TI  - Antimicrobial peptides in defence of the oral and respiratory tracts.
AB  - Antimicrobial peptides (AMPs) are components of complex host secretions, acting
      synergistically with other innate defence molecules to combat infection and
      control resident microbial populations throughout the oral cavity and respiratory
      tract. AMPs are directly antimicrobial, bind lipopolysaccharide (LPS) and
      lipoteichoic acid, and are immunomodulatory signals. Pathogenic and commensal
      organisms display a variety of resistance mechanisms, which are related to
      structure of cell wall components (e.g. LPS) and cytoplasmic membranes, and
      peptide breakdown mechanisms. For example, LPS of the AMP-resistant cystic
      fibrosis pathogen Burkholderia cepacia is under-phosphorylated and highly
      substituted with charge-neutralising 4-deoxy-4-aminoarabinose. Additionally, host
      mimicry by addition of phosphorylcholine contributes to resistance in oral and
      respiratory organisms. Porphyromonas gingivalis, Pseudomonas aeruginosa and other
      pathogens produce extracellular and membrane-bound proteases that degrade AMPs.
      Many of these bacterial properties are environmentally regulated. Their
      modulation in response to host defences and inflammation can result in altered
      sensitivity to AMPs, and may additionally change other host-microbe interactions,
      e.g. binding to Toll-like receptors. The diversity and breadth of antimicrobial
      cover and immunomodulatory function provided by AMPs is central to the ability of
      a host to respond to the diverse and highly adaptable organisms colonising oral
      and respiratory mucosa.

PMID- 14568390
TI  - Regulation of expression of beta-defensins: endogenous enteric peptide
      antibiotics.
AB  - Evidence for the central role that intestinal beta-defensins play in maintaining
      gut health continues to accumulate within the literature. Two epithelially
      derived enteric beta-defensins, hBD1 and hBD2, have been identified thus far and
      the following chapter reviews our current understanding of how the expression and
      secretion of these endogenous antimicrobial, chemotactic and adjuvant peptides is
      regulated within the context of the most microbe-rich of mucosal environments,
      the gastrointestinal tract. The agonists and microbial moieties identified as
      being responsible for the direct receptor-mediated induction of enteric
      epithelial beta-defensins, the signaling and nuclear events that are triggered as
      a consequence and which drive defensin gene transcription, the potential
      antimicrobial and immunomodulatory consequences of beta-defensin release within
      the luminal and mucosal aspects of the alimentary tract thereafter and the
      validity of animal models for the study of these key immune effector molecules in
      vivo are discussed. These significant and recent discoveries have provided much
      in the way of momentum for the pace with which this exciting and dynamic area of
      mucosal immunology research continues to move forward.

PMID- 14568391
TI  - Host anti-microbial response to Helicobacter pylori infection.
AB  - beta-Defensin peptides are known to be potent anti-bacterials with a wide
      spectrum of activity. They, therefore, represent an important aspect of innate
      immunity. In the present study, we have extended our understanding of the
      regulation of the beta-defensins in response to Helicobacter pylori (H. pylori)
      infection. We found elevated levels of hBD2 and hBD3 transcripts within gastric
      cells following infection. This was reflected by increased secretion of the
      corresponding peptide. The relative bactericidal potency of the beta-defensins
      was also assessed. Our findings show that hBD3 was the most potent peptide tested
      followed by hBD2 and hBD1. Relatively modest synergy between hBD1 and hBD2 was
      also noted. More importantly, we observed endogenous production of putative anti
      microbial factors by infected gastric epithelial cells. Our study highlights the
      active participation of the epithelium in protection against potential pathogens.

PMID- 14568392
TI  - Defensins and acne.
AB  - Acne a disease of the pilosebaceous unit is characterised by hypercornification
      and hyperkeratosis of outer root sheath (ORS) and sebaceous duct and perilesional
      infiltrate. Lesions may be characterised as "non"-inflammatory versus
      inflammatory. Hypercornification of the distal ORS and the pilosebaceous duct in
      concert with increased sebum production and abnormalities of the microbial flora
      are considered to be major factors in the pathogenesis of acne vulgaris. However,
      the basic mechanisms involved in the development of inflammation during acne
      vulgaris remain unclear. We have investigated the expression patterns of two
      antimicrobial peptides, human beta-defensin 1 (hBD1) and human beta-defensin 2
      (hBD2) in healthy human hair follicles as well as in peri- and intralesional skin
      of acne vulgaris lesions such as comedones, papules and pustules. Strong hBD1 and
      hBD2 immunoreactivity was found in all suprabasal layers of the epidermis, and
      all permanent compartments of the hair follicle including the distal ORS of the
      hair follicle and the pilosebaceous duct. Moreover, marked hBD1 and hBD2
      expression was also detected in the hair follicle stem cell compartment. In
      contrast, the proximal follicle bulb which undergoes apoptotic regression and is
      also able to regenerate following injury did not express hBD1 or hBD2. The
      majority of acne biopsies displayed a marked upregulation of hBD2 IR in the
      lesional and perilesional epithelium; in particular in pustules, and a less
      marked upregulation of hBD1 IR. The upregulation of beta-defensins expression in
      acne vulgaris lesions when compared to controls suggests that beta-defensins may
      be involved in the pathogenesis of acne vulgaris.

PMID- 14568393
TI  - Alpha-defensins in the gastrointestinal tract.
AB  - The human intestinal tract is constantly exposed to an enormous indigenous
      bacterial flora. It has recently been recognised that antimicrobial peptides of
      the defensin family likely play a role in protection against microbial invasion
      at a variety of mucosal epithelial surfaces, including that of the intestinal
      tract. To date, six alpha-defensins have been identified in humans. Four of
      these, designated Human Neutrophil Peptides (HNP) 1,2,3 and 4, form part of the
      armoury of neutrophils, where they participate in systemic innate immunity. The
      remaining two, Human Defensin (HD) 5 and 6, are expressed in intestinal Paneth
      cells, and probably contribute to innate defense of the GI mucosal surface.
      Murine intestinal alpha-defensins (the 'cryptdins') have been extensively
      studied, but less is known about their human counterparts. The putative mature HD
      5 was chemically synthesised and used to raise polyclonal antiserum. Using this
      anti-HD-5 antiserum, the expression of HD-5 in normal and inflamed intestinal
      mucosal samples was studied using immunohistochemistry. HD-5 is expressed in
      Paneth cells and also in some villous epithelial cells in normal duodenum,
      jejunum and ileum. HD-5 is not expressed in the normal stomach or colon. In cases
      of gastritis, colonic Crohn's disease and ulcerative colitis, HD-5 is expressed
      in metaplastic Paneth cells. Utilizing the anti-HD-5 antiserum, native HD-5 was
      isolated and purified from acid extracts of normal terminal ileal mucosal
      epithelial cells using cation exchange and reverse phase high pressure liquid
      chromatography. The purified peptide was characterised using N-terminal amino
      acid sequence and mass spectral analysis. Antimicrobial activity of the peptide
      was assessed using a sensitive colony forming unit antimicrobial assay. HD-5 is
      stored in the predicted precursor form in Paneth cells, and this form does not
      have antimicrobial activity against a defensin sensitive Salmonella. Potential
      processing of the precursor form of the HD-5 peptide into a mature active form,
      was studied by stimulating Paneth cell granule secretion in freshly isolated,
      cultured ileal crypts. A truncated form of the precursor form of HD-5, but not
      the predicted mature form, was present in the culture supernatant. Recently
      published studies suggest that further processing of the molecule occurs in vivo.
      The expression of HNP 1-3 in the normal intestinal mucosa and in cases of
      inflammatory bowel disease was studied. In the normal intestinal mucosa, HNP are
      expressed only in sparse lamina propria neutrophils, and not in Paneth cells. In
      cases of active ulcerative colitis and Crohn's disease, scattered surface
      epithelial cells, as well as numerous lamina propria neutrophils, were seen to
      express HNP. In conclusion, HD-5 is stored only in its precursor form in normal
      ileal Paneth cells, and partial processing of the peptide to a mature form occurs
      during and/or after secretion. In inflammatory bowel disease, HD-5 is expressed
      in metaplastic Paneth cells in the colon, and HNP is expressed by some surface
      epithelial cells. These studies suggest that antimicrobial defensin peptides may
      be important in protection of the host against microbial invasion in states of
      intestinal inflammation.

PMID- 14568394
TI  - Intestinal defensin gene expression in human populations.
AB  - Defensins are thought to play a major role in the defence of small intestinal
      crypts against colonisation by potential pathogens. In humans two alpha
      defensins, HD5 and HD6 and two beta-defensins, hBD1 and hBD2, probably contribute
      to the antimicrobial barrier, but there are no data to indicate how the
      expression of these defensin genes might vary in individuals and in populations.
      To begin to address this question we developed a competitive reverse
      transcriptase polymerase chain reaction (RT-PCR) assay to quantify HD5 and HD6
      mRNA and used it to measure transcripts in small intestinal biopsy tissue from
      adults living in London, UK, or in Lusaka, Zambia. We also measured alpha- and
      beta-defensin mRNA in biopsies collected in London from different regions of the
      small intestine. Jejunal biopsies (n=169) from 83 adults in Lusaka contained
      approximately one order of magnitude less HD5 and HD6 mRNA than biopsies (n=33)
      obtained from 27 adults in London. HD5 and HD6 transcript levels were high
      throughout duodenum, jejunum and ileum. hBD1 and hBD2 mRNA were detected in some,
      but not all, biopsies from normal small intestine. These data suggest that alpha
      defensin expression is down-regulated in tropical populations, and that there are
      distinct pathways regulating transcription of alpha- and beta-defensins.

PMID- 14568395
TI  - Summary: microbiological perspective.

PMID- 14568396
TI  - An exploratory approach to modeling explosive compound persistence and flux using
      dissolution kinetics.
AB  - Recent advances in the description of aqueous dissolution rates for explosive
      compounds enhance the ability to describe these compounds as a contaminant source
      term and to model the behavior of these compounds in a field environment. The
      objective of this study is to make predictions concerning the persistence of
      2,4,6-trinitrotoluene (TNT) and octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine
      (HMX) in solid form both as individual explosive compounds and components of
      octol, and the resultant concentrations of explosives in water as a result of
      dissolution using three exploratory modeling approaches. The selection of
      dissolution model and rate greatly affect not only the predicted persistence of
      explosive compound sources but also their resulting concentrations in solution.
      This study identifies the wide range in possible predictions using existing
      information and these modeling approaches to highlight the need for further
      research to ensure that risk assessment, remediation and predicted fate and
      transport are appropriately presented and interpreted.

PMID- 14568397
TI  - Preferential flow path development and its influence on long-term PRB
      performance: column study.
AB  - The operating life of an Fe(0)-based permeable reactive barrier (PRB) is limited
      due to chemical reactions of Fe(0) in groundwater. The relative contributions
      from mineral precipitation, gas production, and microbial activity to the
      degradation of PRB performance have been uncertain. In this controlled field
      study, nitrate-rich, site groundwater was treated by Fe(0) in large-volume, flow
      through columns to monitor the changes in chemical and hydraulic parameters over
      time. Tracer tests showed a close relationship between hydraulic residence time
      and pH measurements. The ionic profiles suggest that mineral precipitation and
      accumulation is the primary mechanism for pore clogging around the inlet of the
      column. Accumulated N(2) gas generated by biotic processes also affected the
      hydraulics although the effects were secondary to that of mineral precipitation.
      Quantitative estimates indicate a porosity reduction of up to 45.3% near the
      column inlet over 72 days of operation under accelerated flow conditions.
      According to this study, preferential flow through a PRB at a site with similar
      groundwater chemistry should be detected over approximately 1 year of operation.
      During the early operation of a PRB, pH is a key indicator for monitoring the
      change in hydraulic residence time resulting from heterogeneity development. If
      the surrounding native material is more conductive than the clogged Fe-media,
      groundwater bypass may render the PRB ineffective for treating contaminated
      groundwater.

PMID- 14568398
TI  - Modeling radium and radon transport through soil and vegetation.
AB  - A one-dimensional flow and transport model was developed to describe the movement
      of two fluid phases, gas and water, within a porous medium and the transport of
      226Ra and 222Rn within and between these two phases. Included in this model is
      the vegetative uptake of water and aqueous 226Ra and 222Rn that can be extracted
      from the soil via the transpiration stream. The mathematical model is formulated
      through a set of phase balance equations and a set of species balance equations.
      Mass exchange, sink terms and the dependence of physical properties upon phase
      composition couple the two sets of equations. Numerical solution of each set,
      with iteration between the sets, is carried out leading to a set-iterative
      compositional model. The Petrov-Galerkin finite element approach is used to allow
      for upstream weighting if required for a given simulation. Mass lumping improves
      solution convergence and stability behavior. The resulting numerical model was
      applied to four problems and was found to produce accurate, mass conservative
      solutions when compared to published experimental and numerical results and
      theoretical column experiments. Preliminary results suggest that the model can be
      used as an investigative tool to determine the feasibility of phytoremediating
      radium and radon-contaminated soil.

PMID- 14568399
TI  - A sequential zero valent iron and aerobic biodegradation treatment system for
      nitrobenzene.
AB  - The remediation of nitroaromatic contaminated groundwater is sometimes difficult
      because nitroaromatic compounds are resistant to biodegradation and, when they do
      transform, the degradation of the products may also be incomplete. A simple
      nitroaromatic compound, nitrobenzene, was chosen to assess the feasibility of an
      in situ multi-zone treatment system at the laboratory scale. The proposed
      treatment system consists of a zero valent granular iron zone to reduce
      nitrobenzene to aniline, followed by a passive oxygen release zone for the
      aerobic biodegradation of the aniline daughter product using pristine aquifer
      material from Canadian Forces Base (CFB) Borden, Ontario, as an initial microbial
      source. In laboratory batch experiments, nitrobenzene was found to reduce quickly
      in the presence of granular iron forming aniline, which was not further degraded
      but remained partially sorbed onto the granular iron surface. Aniline was found
      to be readily biodegraded with little metabolic lag under aerobic conditions
      using the pristine aquifer material. A sequential column experiment, containing a
      granular iron reducing zone and an aerobic biodegradation zone, successively
      degraded nitrobenzene and then aniline to below detection limits (0.5 microM)
      without any noticeable reduction in hydraulic conductivity from biofouling, or
      through the formation of precipitates.

PMID- 14568400
TI  - The influence of substrate and electron acceptor availability on bioactive zone
      dynamics in porous media.
AB  - Two approaches were used to investigate the influence of dissolved oxygen (DO)
      and substrate availability on the formation and dynamics of "bioactive zones" in
      a water-saturated porous medium. A bioactive zone is defined as a region where a
      microbial community is sufficiently active to metabolize bioavailable substrates.
      In the first approach, microbial activity was characterized by monitoring the
      spatial and temporal variability of DO and aqueous substrate (salicylate and
      naphthalene) concentrations during miscible-displacement experiments. In the
      second approach, microbial activity was monitored using multiple fiber optics
      emplaced in the porous medium to detect luminescence produced by Pseudomonas
      putida RB1353, a bioluminescent reporter organism that produces light when
      salicylate (an intermediate of naphthalene degradation) is present. The results
      of both approaches show that the location and size of the bioactive zones were
      influenced by in situ DO and substrate availability. When DO was not a limiting
      factor (i.e., lower substrate input concentrations), the bioactive zone
      encompassed the entire column, with the majority of the microbial activity
      occurring between the inlet and midpoint. However, as the availability of DO
      became limiting for the higher substrate input experiments, the size of the
      bioactive zone shrank and was ultimately limited to the proximity of the column
      inlet.

PMID- 14568401
TI  - Modelling of diffusion-limited retardation of contaminants in hydraulically and
      lithologically nonuniform media.
AB  - A new reactive transport modelling approach and examples of its application are
      presented, dealing with the impact of sorption/desorption kinetics on the
      spreading of solutes, e.g. organic contaminants, in groundwater. Slow
      sorption/desorption is known from the literature to be strongly responsible for
      the retardation of organic contaminants. The modelling concept applied in this
      paper quantifies sorption/desorption kinetics by an intra-particle diffusion
      approach. According to this idea, solute uptake by or release from the aquifer
      material is modelled at small scale by a "slow" diffusion process where the
      diffusion coefficient is reduced as compared to the aqueous diffusion coefficient
      due to (i) the size and shape of intra-particle pores and (ii) retarded transport
      of solutes within intra-particle pores governed by a nonlinear sorption isotherm.
      This process-based concept has the advantage of requiring only measurable model
      parameters, thus avoiding fitting parameters like first-order rate coefficients.
      In addition, the approach presented here allows for modelling of slow
      sorption/desorption in lithologically nonuniform media. Therefore, it accounts
      for well-known experimental findings indicating that sorptive properties depend
      on (i) the grain size distribution of the aquifer material and (ii) the
      lithological composition (e.g. percentage of quartz, sandstone, limestone, etc.)
      of each grain size fraction. The small-scale physico-chemical model describing
      sorption/desorption is coupled to a large-scale model of groundwater flow and
      solute transport. Consequently, hydraulic heterogeneities may also be considered
      by the overall model. This coupling is regarded as an essential prerequisite for
      simulating field-scale scenarios which will be addressed by a forthcoming
      publication. This paper focuses on mathematical model formulation, implementation
      of the numerical code and lab-scale model applications highlighting the sorption
      and desorption behavior of an organic contaminant (Phenanthrene) with regard to
      three lithocomponents exhibiting different sorptive properties. In particular, it
      is shown that breakthrough curves (BTCs) for lithologically nonuniform media
      cannot be obtained via simple arithmetic averaging of breakthrough curves for
      lithologically uniform media. In addition, as no analytical solutions are
      available for model validation purposes, simulation results are compared to
      measurements from lab-scale column experiments. The model results indicate that
      the new code can be regarded as a valuable tool for predicting long-term
      contaminant uptake or release, which may last for several hundreds of years for
      some lithocomponents. In particular, breakthrough curves simulated by pure
      forward modelling reproduce experimental data much better than a calibrated
      standard first-order kinetics reactive transport model, thus indicating that the
      new approach is of high quality and may be advantageously used for supporting the
      design of remediation strategies at contaminated sites where some lithocomponents
      and/or grain size classes may provide a long-term pollutant source.

PMID- 14568402
TI  - Estimation of primary drainage three-phase relative permeability for organic
      liquid transport in the vadose zone.
AB  - The modeling of transport of organic liquid contaminants through the vadose zone
      often requires three-phase relative permeabilities. Since these are difficult to
      measure, predictive models are usually used. The objective of this study is to
      assess the ability of eight common models to predict the drainage relative
      permeability to oil in a three-phase system (water-oil-air). A comparison of the
      models' estimates using data set from Oak [Oak, M.J., 1990. Three-phase relative
      permeability of water-wet Berea. In: Seventh Symposium on Enhanced Oil Recovery,
      Paper SPE/Doe 20183. Tulsa, OK, April 22-25] showed that they provide very
      different predictions for the same system. The goodness of the models does not
      increase with the amount of data or computation that the models require. Also,
      the calculations showed how different interpretations of the models and of the
      terminology associated with them can significantly impact the predictions. Thus,
      considerable error may be introduced into the simulations of organic liquid
      transport in the vadose zone depending on the selection and interpretation of the
      three-phase relative permeability model.

PMID- 14568403
TI  - Biodegradable electrospun fibers for drug delivery.
AB  - The influences of surfactants and medical drugs on the diameter size and
      uniformity of electrospun poly(L-lactic acid) (PLLA) fibers were examined by
      adding various surfactants (cationic, anionic, and nonionic) and typical drugs
      into the PLLA solution. Significant diameter reduction and uniformity improvement
      were observed. It was shown that the drugs were capsulated inside of the fibers
      and the drug release in the presence of proteinase K followed nearly zero-order
      kinetics due to the degradation of the PLLA fibers. Such ultrafine fiber mats
      containing drugs may find clinical applications in the future.

PMID- 14568404
TI  - A vesicular shuttle: transport of a vesicle within a flexible microtube.
AB  - Micromanipulation of the external bilayers of nonionic surfactant vesicles
      (niosomes) and liposomes allows the formation of tethers, which are fluid state
      lipid/surfactant lamellar nanotubes. The technique allows investigation of some
      of the factors affecting tether formation and vesicle-tether interactions. In
      this paper the movement of a vesicle along, or more precisely in, tethers derived
      from the vesicle, has been studied. When a vesicle is supported by bipolar
      tethers, stretching the tether on one side of the vesicle, initiates the movement
      of the vesicle in the opposite direction, at velocities ranging up to 2.5 microm
      s(-1) thus creating a 'vesicular shuttle'. Movement of the vesicle occurs inside
      the tether structures, a process akin to the movement of a sphere in a flexible
      tube with a diameter much less than that of the sphere. The factors involved in
      the movement of vesicles in the tethers include the radial stretching and
      subsequently contraction of the tethers and the minimisation of elastic energies
      stored in the tether membranes. Vesicle velocity is not constant: there is
      deceleration near the end of the trajectory. While the relevance to the design of
      novel delivery systems is as yet tenuous, the system allows vesicle-vesicle
      collisions to be observed when the vesicle is propelled towards a stationary
      vesicle, and directly observation of the flow properties of vesicles in flexible
      'capillaries', a neglected topic.

PMID- 14568405
TI  - One-side-coated insert as a unique ophthalmic drug delivery system.
AB  - We newly prepared a unique one-side-coated insert that releases drug from only
      uncoated side. The purpose of this study is to determine whether ocular and
      systemic absorption of ophthalmic drug could be altered by an inserting direction
      of the insert in rabbit eyes. One-side-coated insert was prepared by attaching a
      polypropylene tape on the one side of the polymer disc of poly(2-hydroxypropyl
      methacrylate) (HPM) containing tilisolol as a model ophthalmic drug. The insert
      was applied in the lower conjunctival cul-de-sac of albino rabbits with the
      uncoated side facing bulbar conjunctiva/sclera (SC insert) or palpebral
      conjunctiva (CJ insert). At the adequate intervals, the tear fluid, plasma,
      aqueous humor, conjunctiva, and sclera were collected and the drug concentrations
      were determined by an HPLC. A release of tilisolol from the one-side-coated
      insert was twice slower than from the uncoated insert. Ocular application of the
      one-side-coated insert produced the constant concentrations of tilisolol in the
      tear fluid over 180 min. SC insert showed higher drug concentrations in the
      aqueous humor and sclera, and lower drug concentrations in the plasma and
      conjunctiva than CJ insert.The one-side-coated insert can alter the ocular and
      systemic absorption of drug by an inserting direction.

PMID- 14568406
TI  - Effects of crystalline microstructure on drug release behavior of poly(epsilon
      caprolactone) microspheres.
AB  - This study investigates the release behavior of papaverine from poly(epsilon
      caprolactone) (PCL) microparticles prepared by the oil/water solvent evaporation
      method. Microparticles were characterized in terms of crystalline morphology,
      size, drug loading, and encapsulation efficiency by using differential scanning
      calorimetry (DSC), small angle X-ray scattering (SAXS), scanning electron
      microscopy (SEM), and UV spectrometry. The release behavior of papaverine was
      governed by the microstructure of PCL microparticles, suggesting that the
      environment for diffusion changes according to processing conditions such as
      polymer solution concentration, thermal history, and polymer molecular weight. As
      the PCL solution concentration increased, the drug release behavior showed a more
      sustained pattern. This result indicates that the size of the PCL microparticles
      is a determining factor for drug release. And when higher PCL molecular weight is
      used for preparation of microparticles, it led to a rapid release. Furthermore, a
      more delayed pattern of drug release profile was obtained in the sample prepared
      with higher thermal treatment. These results suggest that the crystalline
      microstructure of PCL microparticles plays an important role in its drug release
      behavior.

PMID- 14568407
TI  - Azulene incorporation and release by hydrogel containing methacrylamide
      propyltrimenthylammonium chloride, and its application to soft contact lens.
AB  - We have developed the epoch-making contact lens that is equipped with drug
      delivery system. The hydrogels contain cationic functional group in its side
      chain were prepared with 2-hydroxyethyl methacylate (HEMA) and methacrylamide
      propyltrimethylammonium chloride (MAPTAC). The obtained hydrogel is capable to
      store the anionic drug such as azulene based on ion-exchange reaction. The
      incorporated anionic drug would be released in physiological condition. The size
      change of the hydrogel may occur before and after drug release, but we have
      discovered that the addition of anionic monomer such as methacrylic acid (MAA)
      and 2-methacryloxyethyl acid phosphate (MOEP) to the above-mentioned composition
      is effective to prevent the size change, indicating that this hydrogel has the
      possibility to be applied as a significant drug delivery system device.

PMID- 14568408
TI  - Liposome delivery of ciprofloxacin against intracellular Francisella tularensis
      infection.
AB  - The effect of liposome delivery on the controlled release and therapeutic
      efficacy of ciprofloxacin against intracellular Francisella tularensis infection
      in vivo was evaluated in this study. Ciprofloxacin was encapsulated in small
      unilamellar vesicles by a remote loading procedure using an ammonium sulfate
      gradient. This procedure produced uniform sized liposomes (100 nm) with an
      entrapment rate of 90+/-3.5%. Following administration of unencapsulated or
      liposome-encapsulated ciprofloxacin by intravenous injection or aerosol
      inhalation, levels of ciprofloxacin in sera, lungs, liver and spleen were
      determined using 14C-ciprofloxacin as radiotracer for ciprofloxacin. Intravenous
      injection of liposome-encapsulated ciprofloxacin resulted in higher serum levels
      of drug in serum, as well as increased drug retention in lungs, liver and spleen,
      compared to that of free encapsulated drug. Aerosol administration of liposome
      encapsulated ciprofloxacin by jet nebulization resulted in significantly higher
      drug levels and prolonged drug retention in the lower respiratory tract compared
      to the free drug. Aerosol inhalation of liposome-encapsulated ciprofloxacin,
      given either prophylactically or therapeutically, provided complete protection to
      mice against a pulmonary lethal infection model of F. tularensis. In contrast,
      ciprofloxacin given in its free form, was ineffective. These results suggest that
      liposome encapsulation of ciprofloxacin enhances drug delivery to the primary
      site of infection and results in increasing therapeutic efficacy against F.
      tularensis.

PMID- 14568409
TI  - Theoretical and experimental study on theophylline release from stearic acid
      cylindrical delivery systems.
AB  - The purpose of this study is to evaluate the possibility of developing a
      cylindrical sustained-release dosage form for theophylline directly by means of a
      ram extrusion process. In particular, the formulations contained: stearic acid as
      a low melting binder, monohydrate lactose and polyethylene glycol 6000 as
      hydrophilic fillers. The influence of type and percentage of the components was
      studied considering different parameters such as the time required for 50% of the
      drug release (t50%)and the drug diffusion coefficient in the delivery system. The
      choice of the different formulations to be tested is carried out employing an
      axial design with constraint domains. The limits of each component were fixed on
      the basis of preliminary trials. The analysis of the t50% values revealed that
      the release kinetics is mainly affected by stearic acid and theophylline content,
      whilst lactose effect is almost negligible. A substantial correspondence between
      the experimental results and the analysis of the drug release kinetics performed
      by means of an ad hoc developed mathematical model was found. The proposed
      mathematical model allows to conclude that wherever the release mechanism is
      initially ruled by dissolution, then diffusion plays the most important role.

PMID- 14568410
TI  - Monitoring of peptide acylation inside degrading PLGA microspheres by capillary
      electrophoresis and MALDI-TOF mass spectrometry.
AB  - The purpose of this research was to assess the acylation reactions of peptides,
      salmon calcitonin (sCT), human parathyroid hormone 1-34 (hPTH1-34) and
      leuprolide, in poly(lactic-co-glycolic acid) (PLGA) microspheres. Capillary
      electrophoresis (CE) and matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry (MALDI-TOF MS) were used for determining and monitoring
      peptide acylation and quantitating acylation products in the degrading PLGA
      microspheres. In the degrading PLGA microspheres of sCT and hPTH1-34, the
      acylation products were observed and determined to be adducts with glycolic acid
      units from degradable PLGA polymer by MALDI-TOF MS. In the microsphere of
      leuprolide, however, the acylation product was not observed even after 28 days of
      incubation at the release medium, which represents the different stabilities
      among peptides according to the primary structure. As the leuprolide contains
      tyrosine and serine having hydroxyl group of nucleophilic amino acids, the
      acylation reaction of peptide is shown to be mainly due to the primary amino
      groups of N-terminus or lysine residue. The complementary use of CE and MALDI-TOF
      MS will be useful for searching the counter measures as well as determining the
      peptide acylation in the manufactured formulations on the market.

PMID- 14568411
TI  - In vivo anti-tumor effect through the controlled release of cisplatin from
      biodegradable gelatin hydrogel.
AB  - This paper is an investigation to achieve the in vivo controlled release of
      cisplatin (CDDP) from a biodegradable hydrogel. Hydrogels with different water
      contents were prepared through the chemical crosslinking of gelatin by various
      concentrations of glutaraldehyde. The gelatin hydrogel incorporating CDDP (CDDP
      hydrogel) was prepared by allowing CDDP aqueous solution to sorb into the freeze
      dried hydrogel. Irrespective of the hydrogel water content, approximately 10-30%
      of incorporated CDDP was released from the hydrogel in phosphate-buffered saline
      solution (PBS) at 37 degrees C within the initial 6 h, while little release was
      observed thereafter. The amount of CDDP released initially decreased with an
      increase in the time period of CDDP sorption. When intratumorally applied into
      Meth-AR-1 tumor-bearing mice, CDDP-hydrogel suppressed in vivo tumor growth to a
      significantly higher extent than free CDDP at the same dose. The survival rate
      was significantly higher by the application of CDDP-hydrogel of 40 microg CDDP.
      The CDDP concentration in the tumor tissue was maintained at a higher level for a
      longer time period than that of free CDDP. However, no problematic change in the
      mouse body and blood biochemical parameters was observed on the application of
      the CDDP-hydrogel. The time course of in vivo CDDP retention was in a good
      accordance with that of hydrogel remaining. Larger CDDP release was observed from
      the front surface of hydrogel onto which free CDDP was sorbed, than the back
      surface of hydrogel. These findings demonstrate that the controlled release of
      CDDP was based on biodegradation of the hydrogel carrier, but not simple
      diffusion of CDDP. It is possible that the CDDP molecules immobilized in the
      gelatin hydrogel were released from the hydrogel only when the hydrogel was
      degraded to generate some water-soluble gelatin fragments.

PMID- 14568413
TI  - Theoretical investigation of drug release from planar matrix systems: effects of
      a finite dissolution rate.
AB  - Drug release from planar matrix systems has been investigated with special
      emphasis on the influence of a finite dissolution rate on the drug release
      profile. A mathematical model of the drug dissolution and release processes was
      formulated in terms of two coupled nonlinear partial differential equations
      (PDEs). These were solved numerically by using well-established FORTRAN routines.
      An approximate analytical solution, valid during the early stages of the release
      process, was derived. The analytical solution was compared to the numerical one
      and to drug release models existing in the literature. From this comparison, it
      was established that the analytical approximation provided a good description of
      the major part of the release profile, irrespective of the dissolution rate.
      Existing literature models, based on instantaneous dissolution, were found to
      agree with the numerical solution only when drug dissolution proceeded very
      rapidly in comparison with the diffusion process. Consequently, the new
      analytical short-time approximation of the drug release complements the formulas
      existing in the literature, since it provides a superior description of the
      release of slowly dissolving drugs.

PMID- 14568412
TI  - HPMA copolymer-bound doxorubicin targeted to tumor-specific antigen of BCL1 mouse
      B cell leukemia.
AB  - N-(2-Hydroxypropyl)methacrylamide (HPMA) copolymer carrier containing the
      anticancer drug doxorubicin and targeted with B1 monoclonal antibody (mAb) to
      BCL1 leukemia cells was synthesised and tested in vitro and in vivo. BCL1
      leukemia growing in syngenic Balb/c mice was selected as a tumor model system. B1
      mAb recognising the idiotype of surface IgM on BCL1 cells was used as a targeting
      moiety. Both B1 mAb and doxorubicin were conjugated to HPMA copolymer carrier by
      aminolysis through a tetrapeptidic Gly-Phe(D,L)-Leu-Gly spacer to ensure the
      intracellular delivery and controlled release of the drug. B1 mAb-targeted
      conjugate was shown to possess strictly tumor-specific binding capacity to target
      BCL1 cells in vitro. A similar conjugate, but containing human nonspecific Ig
      (HuIg) instead of B1 mAb, failed to bind to BCL1 cells. In vitro, B1 mAb-targeted
      conjugate demonstrated 40-fold higher cytotoxic effect than nontargeted or human
      nonspecific Ig-containing HPMA copolymer-bound doxorubicin. Conjugate targeted
      with B1 mAb was also shown to bind to target BCL1 cells in vivo. B1 mAb-targeted
      conjugate was shown to be more efficient in the treatment of established BCL1
      leukemia than free doxorubicin, nontargeted and human nonspecific Ig-containing
      conjugate. Antibody-targeted polymeric drugs are thus promising conjugates for
      cancer treatment.

PMID- 14568414
TI  - Investigating the coating-dependent release mechanism of a pulsatile capsule
      using NMR microscopy.
AB  - Chronopharmaceutical capsules, ethylcellulose-coated to prevent water ingress,
      exhibited clearly different release characteristics when coated by organic or
      aqueous processes. Organic-coated capsules produced a delayed pulse release,
      whereas aqueous-coated capsules exhibited less delayed and more erratic release
      behaviour. Nuclear magnetic resonance microscopy was used to elucidate the
      internal mechanisms underlying this behaviour by studying the routes of internal
      water transport and the timescale and sequence of events leading to the pulse.
      Images showed that the seal between the shell and the tablet plug is a key route
      of water penetration in these dosage forms. There is evidence for a more
      efficient seal in the organic-coated capsule, and although some hydration of the
      contents was evident, erosion of the tablet plug is most probably the controlling
      factor in timed release. The premature failure of the aqueous-coated capsule
      appears to be a result of rapid influx of water between plug and capsule with
      hydration of the low substituted hydroxypropylcellulose expulsion agent. As a
      result of this, the tablet plug remains intact, but appears unable to be ejected.
      The resulting significant pressure build-up causes premature release by
      distortion and splitting of the capsule shell. These events may be aided by a
      weakening of the aqueous-coated gelatin shell by hydration from the inside, and
      at the mouth of the capsule where previous electron microscope studies have shown
      incomplete coating of the inside by the aqueous process.

PMID- 14568415
TI  - Incorporation of drugs in an amorphous state into electrospun nanofibers composed
      of a water-insoluble, nonbiodegradable polymer.
AB  - Electrostatic spinning was applied to the preparation of drug-laden
      nonbiodegradable nanofiber for potential use in topical drug administration and
      wound healing. The specific aim of these studies was to assess whether these
      systems might be of interest as delivery systems for poorly water-soluble drugs.
      Itraconazole and ketanserin were selected as model compounds while a segmented
      polyurethane (PU) was selected as the nonbiodegradable polymer. For both
      itraconazole and ketanserin, an amorphous nanodispersion with PU was obtained
      when the drug/polymer solutions were electrospun from dimethylformide (DMF) and
      dimethylacetamide (DMAc), respectively. The collected nonwoven fabrics were shown
      to release the drugs at various rates and profiles based on the nanofiber
      morphology and drug content. Data were generated using a specially designed
      release apparatus based around a rotating cylinder. At low drug loading,
      itraconazole was released from the nanofibers as a linear function of the square
      root of time suggesting Fickian kinetics. No initial drug burst was observed. A
      biphasic release pattern was observed for ketanserin in which two sequential
      linear components were noted. These release phases may be temporally correlated
      with (1) drug diffusion through the polymer and (2) drug diffusion through formed
      aqueous pores.

PMID- 14568416
TI  - Controlled release with coating layer of permeable particles.
AB  - An enhanced method was proposed for controlled release of core material using a
      coating layer of fine permeable particles dispersed in an impermeable wax
      prepared by dry-based process. A mathematical model was constructed to describe
      in detail the core material release by diffusion through the connected permeable
      particles inside the coating layer. The effective diffusivity was simulated by a
      random walk method taking into account the structure of the coating layer. The
      released characteristics were measured for the urea core particle coated with the
      layer of the starch permeable particles dispersed in the paraffin wax. The
      calculated results were in a good quantitative agreement with experimental data
      in all range of coating conditions. As a result, the low release rate was proven
      to be obtained with thicker coating layer of lower volume fraction of permeable
      particles. Moreover, the application of permeable particles instead of soluble
      ones [J. Chem. Eng. Jpn. 35 (2002) 40] resulted in significant decrease in
      release rate.

PMID- 14568417
TI  - Increased release of gentamicin from acrylic bone cements under influence of low
      frequency ultrasound.
AB  - The release profile of antibiotics from antibiotic-loaded bone cement, used to
      prevent infections in total joint arthroplasty, is neither ideal nor complete.
      Ultrasound has been used to allow drugs to cross otherwise impermeable barriers.
      The aim of this study was to establish a possible effect of ultrasound on
      antibiotic release from bone cements. Samples were made of three commercially
      available gentamicin-loaded bone cements. Part of the samples was allowed to
      release gentamicin for 3 weeks before insonation. An insonation device produced
      an ultrasound field with a time average acoustic intensity of 167 mW/cm2 at a
      frequency of 46.5 kHz. The samples were exposed to the ultrasound field or not
      exposed to it as a control. The amount of gentamicin released was measured by
      fluorescence polarization immunoassay. There was a limited increase of gentamicin
      release with application of ultrasound in fresh samples but not in the samples
      that had been allowed to release gentamicin. For fresh samples, a linear
      regression model showed that this ultrasound effect was statistically
      significant. The mechanism behind these observations is not clear, but it is
      suggested that microstreaming or localized temperature rises may be involved.

PMID- 14568418
TI  - A water-insoluble drug monolithic osmotic tablet system utilizing gum arabic as
      an osmotic, suspending and expanding agent.
AB  - A monolithic osmotic tablet system (MOTS) with two orifices in both side surfaces
      has been studied. Water-insoluble naproxen was selected as the model drug. Gum
      arabic was used as an osmotic, suspending and expanding agent, and cellulose
      acetate (CA) was used as semipermeable membrane. Polyethylene glycol 400 (PEG
      400) was employed as plasticizer for controlling membrane porosity. The
      influences of gum arabic, PEG-400, membrane thickness and orifice size on the
      naproxen release profiles were investigated, and the optimal MOTS was evaluated
      in different environment media and stirring rates. The optimal MOTS was found to
      be able to deliver naproxen at a rate of approximately zero order up to 12 h in
      pH 6.8, cumulative release at 12 h is 81%, independent on environment media and
      stirring rate. Therefore, this MOTS can be used in oral drug-controlled delivery
      field, especially for water-insoluble drug.

PMID- 14568419
TI  - Targeted gene delivery into HepG2 cells using complexes containing DNA,
      cationized asialoorosomucoid and activated cationic liposomes.
AB  - Unilamellar activated cationic liposomes containing 3beta[N-(N',N'
      dimethylaminopropane)-carbamoyl] cholesterol, dioleoyl phosphatidylethanolamine
      (DOPE) and the N-hydroxysuccinimide ester of cholesteryl hemisuccinate (4:5:1,
      molar ratio) have been prepared and their DNA-binding capacity has been assessed
      in a gel retardation assay. Ternary complexes composed of activated cationic
      liposomes, carbodiimide-cationized asialoorosomucoid (Me+AOM) and pRSVL plasmid
      DNA were assembled for receptor-mediated DNA delivery into cells expressing the
      asialoglycoprotein receptor (ASGP-R). Binding of complexes in which Me+AOM was
      replaced by fluoresceinated Me+AOM (FMe+AOM) to the human hepatocellular cell
      line HepG2 at 4 degrees C was severely reduced by co-incubation with
      asialoorosomucoid (AOM). Moreover, assemblies containing liposomes, pRSVL DNA and
      Me+AOM (8:1:4, w/w/w) promoted high levels of luciferase activity in this cell
      line (1.3 x 10(7) relative light units/mg soluble cell protein). Assays conducted
      in the presence of a hundred-fold excess of the ligand AOM afforded considerably
      lower levels of transfection (2.5 x 10(5) relative light units/mg soluble cell
      protein). In contrast, the highest level of luciferase activity achieved with
      liposome, pRSVL DNA, AOM complexes was only a quarter of the best levels obtained
      with liposome, pRSVL DNA, Me+AOM assemblies. These findings strongly support the
      notion that complexes gain entry into hepatocyte-derived cells by ASGP-R
      mediation and that they are potentially useful gene carriers to liver
      hepatocytes.

PMID- 14568420
TI  - Encapsulation of Ole e 1 in biodegradable microparticles induces Th1 response in
      mice: a potential vaccine for allergy.
AB  - Ole e 1 is the most prevalent allergen of olive (Olea europaea) pollen. The
      suitability of poly(D,L-lactide-co-glycolide) (PLG) microparticles as a vaccine
      delivery system for Ole e 1 in therapy against olive allergy has been evaluated.
      BALB/c mice were immunized intraperitoneally with Ole e 1 in PLG microparticles.
      Encapsulated Ole e 1 induced specific and long-lasting antibodies that were
      predominantly of the IgG2a isotype. Splenic cells from immunized mice secreted in
      vitro IFN-gamma, but not IL-4, after stimulation with Ole e 1. These results
      suggest that Ole e 1-containing PLG microparticles elicit a specific Th1-type
      immune response and may become a promising concept for allergy vaccine.

PMID- 14568423
TI  - Surface modification of a segmented polyetherurethane using a low-powered gas
      plasma and its influence on the activation of the coagulation system.
AB  - A medical grade segmented polyetherurethane (PEU) was treated with a low-powered
      gas plasma using O(2), Ar, N(2) and NH(3) as the treatment gases. Changes in the
      surface functional group chemistry were studied using X-ray photoelectron
      spectroscopy. The wettability of the surfaces was examined using dynamic contact
      angle measurements and the surface morphology was evaluated using atomic force
      microscopy. The influence of the surface modification to the polyurethane on the
      blood response to the polyetherurethane was investigated by measuring changes in
      the activation of the contact phase activation of the intrinsic coagulation
      cascade. The data demonstrate that the plasma treatment process caused surface
      modifications to the PEU that in all cases increased the polar nature of the
      surfaces. O(2) and Ar plasmas resulted in the incorporation of oxygen-containing
      groups that remained present following storage in an aqueous environment. N(2)
      and NH(3) plasmas resulted in the incorporation of nitrogen-containing groups but
      these were replaced with oxygen-containing groups following storage in the
      aqueous environment. In all plasma treatments there was a lowering of contact
      phase activation compared to the untreated surface, the N(2) and NH(3) treatments
      dramatically so.

PMID- 14568425
TI  - Bone mineral change during experimental heating: an X-ray scattering
      investigation.
AB  - The effects of heating and burning on bone mineral have previously been studied
      using techniques such as X-ray diffraction (XRD) with the aim of discerning a
      characteristic signature of crystal change. This would enable a better
      understanding of alteration to bone mineral during heating, which would in turn
      impact on the preparation and use of natural bone hydroxyapatite as a biomaterial
      resource. In addition, this knowledge could prove invaluable in the investigation
      of burned human remains from forensic and archaeological contexts in cremation
      and funerary practice. Here we describe a complementary method, small-angle X-ray
      scattering (SAXS), to determine more accurately the changes to bone crystallite
      size and shape during an experimental heating regimen. Samples were subjected to
      controlled heating at 500 degrees C, 700 degrees C, or 900 degrees C for 15 or 45
      min. Our results show bone crystallites begin to alter in the first 15 min of
      heating to 500 degrees C or above. They then appear to stabilise to a temperature
      specific thickness and shape with prolonged heating. While the samples heated to
      lower temperatures or for shorter periods produce XRD traces showing little
      alteration to the apatite, corresponding information obtained from SAXS shows an
      early, subtle change in crystal parameters.

PMID- 14568424
TI  - Glial cell and fibroblast cytotoxicity study on plasma-deposited diamond-like
      carbon coatings.
AB  - Diamond-like carbon films have been evaluated as coatings to improve
      biocompatibility of orthopedic and cardiovascular implants. This study initiates
      a series of investigations that will evaluate diamond-like carbon (DLC) as a
      coating for improved biocompatibility in chronic neuroprosthetic implants.
      Studies in this report assess the cytotoxicity and cell adhesion behavior of DLC
      coatings exposed to glial and fibroblast cell lines in vitro. It can be concluded
      from these studies that DLC coatings do not adversely affect 3T3 fibroblast and
      T98-G glial cell function in vitro. We also successfully rendered DLC coatings
      non-adhesive (no significant fibroblast or glial cell adhesion) with surface
      immobilized dextran using methods developed for other biomaterials and
      applications. Future work will further develop DLC coatings on prototype
      microelectrode devices for chronic neural implant applications.

PMID- 14568426
TI  - Development of collagenase-resistant collagen and its interaction with adult
      human dermal fibroblasts.
AB  - Collagen is regarded as one of the most useful biomaterials. The excellent
      biocompatibility and safety due to its biological characteristics, such as
      biodegradability and weak antigenecity, made collagen the primary source in
      biomedical application. Collagen has been widely used in the crosslinked form to
      extend the durability of collagen. The chemical treatment influences the
      structural integrity of collagen molecule resulting in the loss of triple helical
      characteristic. The structural characteristic of collagen is importantly related
      to its biological function for the interaction with cell. In this study,
      structural stability of collagen was enhanced thought EGCG treatment, resulting
      in high resistance against degradation by bacterial collagenase and MMP-1, which
      is confirmed by collagen zymography. The triple helical structure of EGCG-treated
      collagen could be maintained at 37 degrees C in comparison with collagen, which
      confirmed by CD spectra analysis, and EGCG-treated collagen showed high free
      radical scavenging activity. Also, with fibroblasts culture on EGCG-treated
      collagen, the structural stability of EGCG-treated collagen provided a favorable
      support for cell function in cell adhesion and actin filament expression. These
      observations underscore the need for native, triple helical collagen conformation
      as a prerequisite for integrin-mediated cell adhesion and functions. According to
      this experiment, EGCG-treated collagen assumes to provide a practical benefit to
      resist the degradation by collagenase retaining its structural characteristic,
      and can be a suitable biomaterial for biomedical application.

PMID- 14568427
TI  - Nanostructured Ti-based multi-component alloys with potential for biomedical
      applications.
AB  - A group of Ti(60)Cu(14)Ni(12)Sn(4)M(10) (M=Nb, Ta, Mo) alloys was prepared using
      arc melting and copper mold casting. The as-prepared alloys have a composite
      microstructure containing a micrometer-sized dendritic beta-Ti(M) phase dispersed
      in a nanocrystalline matrix. These new alloys exhibit a low Young's modulus in
      the range of 59-103 GPa, and a high yield strength of 1037-1755 MPa, together
      with large plastic strains. The combination of high strength and low elastic
      modulus offers potential advantages in biomedical applications.

PMID- 14568428
TI  - Frictional properties of poly(MPC-co-BMA) phospholipid polymer for catheter
      applications.
AB  - A fundamental understanding of surface properties of the biomaterials at a
      nanometer scale should be generated in order to understand cellular responses of
      the tissue to biomaterials thereby minimizing or eliminating tissue trauma at a
      macrometer scale. In this study poly(2-methacryloyloxyethyl phosphorylcholine-co
      n-butyl methacrylate) ([poly(MPC-co-BMA]) was evaluated as a potential coating
      material for vascular applications to provide smooth catheterization using atomic
      force microscopy (AFM) techniques.A uniform coating of [poly(MPC-co-BMA]
      equivalent to a thickness of 2.5 microm on a polyurethane (PU) catheter material
      was provided using dip casting technique. Using a contact mode AFM, no
      significant difference in surface roughness (R(a)) and frictional force (f)
      between uncoated (R(a)=10.2+/-1.9 nm, f=0.907+/-0.02) and coated (R(a)=11.7+/-1.8
      nm, f=0.930+/-0.06) surfaces was observed under dry conditions. However, under
      wet conditions the R(a) of the coated surface (3.4+/-1.0 nm) was significantly
      lower than uncoated PU surface (9.0+/-1.8 nm). The coating on PU substrate
      offered the least frictional resistance (f=0.004+/-0.001) illustrating enhanced
      boundary lubrication capability due to hydration of phosphorylcholine polymer as
      compared to a significantly higher f for uncoated PU (0.017+/-0.007) surfaces.
      These tribological and chemical characteristics of the [poly(MPC-co-BMA)] coating
      could increase the overall efficacy of PU for clinical applications.

PMID- 14568429
TI  - Effect of post-deposition heating temperature and the presence of water vapor
      during heat treatment on crystallinity of calcium phosphate coatings.
AB  - In this study, radiofrequency sputtered calcium phosphate (CaP) coatings were
      evaluated after 1h post-deposition heat treatment at either 350 degrees C, 400
      degrees C, 450 degrees C, 500 degrees C or 600 degrees C in the presence or
      absence of water vapor. X-ray diffraction analyses indicated the as-sputtered
      coatings to be amorphous. With different post-deposition heat treatments used, in
      this study, crystallinity of CaP coatings was observed to be in the range of 0
      68%. The 400 degrees C and 450 degrees C heat-treated CaP coatings in the absence
      of water vapor were poorly crystalline, exhibiting a crystallinity of 2+/-1%. In
      comparison to heat treatments at 450 degrees C in the absence of water vapor, the
      presence of water vapor at 450 degrees C heat treatment resulted in a significant
      increase in coating crystallinity. However, this effect was not observed at
      higher temperatures. A coating crystallinity of 60-68% was observed for coatings
      heat treated at 450 degrees C in the presence of water vapor, and at 500 degrees
      C and 600 degrees C in the presence or absence of water vapor. In addition,
      increases in the degree of coating crystallinity were observed to be consistent
      with the increasing number of PO(4) peaks observed as a result of different post
      deposition heat treatments. It was concluded that the presence of water vapor at
      450 degrees C post-deposition heat treatment significantly affect the
      crystallinity of CaP coatings, whereas an increase to temperature higher than 450
      degrees C and in the presence of water vapor has no significant effect on
      crystallinity.

PMID- 14568430
TI  - Adhesion and proliferation of human endothelial cells on photochemically modified
      polytetrafluoroethylene.
AB  - We studied the adhesion and proliferation of human endothelial cells on
      photochemically modified polytetrafluoroethylene samples. The polymer surfaces
      were modified by exposure to the ultraviolet light of a Xe(2)(*)-excimer lamp at
      a wavelength of 172 nm in an ammonia atmosphere. Treatment times were between 10
      and 20 min. The endothelial cell density was determined 1, 3 and 8 days after
      seeding by image analysis. Surface modification of the samples resulted in a
      significant increase in the number of adhering cells and in the formation of a
      confluent cell layer after 3-8 days. The results were comparable than those
      obtained on polystyrene Petri dishes, which are used as standard substrates in
      cell cultivation. Thus modified PTFE appears to be a promising material for the
      fabrication of artificial vascular prostheses coated with endothelial cells.

PMID- 14568431
TI  - Determination of the activation energies of and aggregate rates for exothermic
      physico-chemical changes in UHMWPE by isothermal heat-conduction microcalorimetry
      (IHCMC).
AB  - Exothermic heat flow rates (Q=microW=microJ/s), as a function of elapsed time,
      were measured by isothermal heat-conduction microcalorimetry (IHCMC) in order to
      study the aggregate rate of physico-chemical change in specimens of unsterilized
      and sterilized ultra-high-molecular-weight polyethylene (UHMWPE). Standard
      protocols for performing the IHCMC tests were developed and are described. Use of
      the standard protocols yielded the desired results-data that were not
      significantly different among either replicate sets of unsterilized specimens or
      as a function of which calorimeter test well was used. Heat flow rates measured
      in air at 20 degrees C, 25 degrees C, 35 degrees C, and 45 degrees C yielded
      estimates of activation energies of 47, 11, and 41 kJ/mol for unsterilized, gamma
      radiation sterilized, and ethylene oxide gas (EtO) sterilized polymer,
      respectively. These results support the ideas that (a). initial exothermic
      degradation takes place much more easily in the radiation-sterilized material,
      due to direct oxidation of readily available free radicals, and (b). the much
      slower degradation process in EtO-sterilized UHMWPE is not appreciably different
      than in unsterilized polymer. Comparison with other activation energy data
      suggests that the rate-limiting process in EtO- or un-sterilized polymer is
      oxygen diffusion into the polymer. For shelf storage in air, for periods up to 8
      months, the mean exothermic heat flow in air, at 25 degrees C (Q(m)) [determined
      from the Q values averaged over the time period between 15 and 20 h after test
      start], from UHMWPE gamma-radiation sterilized in air was significantly higher
      than for unsterilized material (2.91+/-0.11 vs. 0.73+/-0.11 microW). The higher
      rate can be attributed to oxidation of radiation-induced free radicals in the
      polymer near its surface. For the gamma-irradiated polymer, the decline in Q(m)
      with shelf storage time suggests that, eventually, degradation might become
      oxygen diffusion limited in this case also. However, in vivo, surface wear of an
      UHMWPE articular component may continue to expose unoxidized free radicals,
      keeping the exothermic reaction rate high and, possibly, continuing to produce an
      oxidized UHMWPE surface prone to wear.

PMID- 14568432
TI  - Expansion of human nasal chondrocytes on macroporous microcarriers enhances
      redifferentiation.
AB  - Articular cartilage has a limited capacity for self-repair. To overcome this
      problem, it is expected that functional cartilage replacements can be created
      from expanded chondrocytes seeded in biodegradable scaffolds. Expansion of
      chondrocytes in two-dimensional culture systems often results in
      dedifferentiation. This investigation focuses on the post-expansion phenotype of
      human nasal chondrocytes expanded on macroporous gelatin CultiSpher G
      microcarriers. Redifferentiation was evaluated in vitro via pellet cultures in
      three different culture media. Furthermore, the chondrogenic potential of
      expanded cells seeded in polyethylene glycol terephthalate/ polybuthylene
      terephthalate (PEGT/PBT) scaffolds, cultured for 14 days in vitro, and
      subsequently implanted subcutaneously in nude mice, was assessed. Chondrocytes
      remained viable during microcarrier culture and yielded doubling times (1.07+/
      0.14 days) comparable to T-flask expansion (1.20+/-0.36 days). Safranin-O
      staining from pellet culture in different media demonstrated that production of
      GAG per cell was enhanced by microcarrier expansion. Chondrocyte-polymer
      constructs with cells expanded on microcarriers contained significantly more
      proteoglycans after subcutaneous implantation (288.5+/-29.2 microg) than those
      with T-flask-expanded cells (164.0+/-28.7 microg). Total collagen content was
      similar between the two groups. This study suggests that macroporous gelatin
      microcarriers are effective matrices for nasal chondrocyte expansion, while
      maintaining the ability of chondrocyte differentiation. Although the exact
      mechanism by which chondrocyte redifferentiation is induced through microcarrier
      expansion has not yet been elucidated, this technique shows promise for cartilage
      tissue engineering approaches.

PMID- 14568433
TI  - The use of biodegradable polyurethane scaffolds for cartilage tissue engineering:
      potential and limitations.
AB  - The aim of the present study was to evaluate the capability of novel
      biodegradable polyurethane scaffolds to support attachment, growth and
      maintenance of differentiated chondrocytes in vitro for up to 42 days. After an
      initial decrease, although not significant, the DNA content of the constructs
      remained constant over the culture time. A progressive increase in
      glycosaminoglycans and collagen was observed during the culture period. However,
      a significant release of matrix molecules into the culture medium was also
      noticeable. At the transcriptional level, a decrease in aggrecan and procollagen
      II mRNA expression was noticeable, whereas procollagen I expression was
      increased. To conclude, the present data demonstrate that biodegradable
      polyurethane porous scaffolds seeded with articular chondrocytes support cell
      attachment and the production of extracellular matrix proteins. The limitations
      of the system are the diffusion of large amounts of matrix molecules into the
      culture medium and the dedifferentiation of the chondrocytes with prolonged time
      in culture. However, due to the favourable mechanical properties of the
      polyurethane scaffold, stimulation of chondrocytes by mechanical loading can be
      considered in order to improve the formation of a functional cartilage-like
      extracellular matrix.

PMID- 14568434
TI  - Calcium phosphate formation and ion dissolution rates in silica gel-PDLLA
      composites.
AB  - Sol-gel derived silicas are potential biomaterials both for tissue regeneration
      and drug delivery applications. In this study, both SiO(2) and calcium and
      phosphate-containing SiO(2) (CaPSiO(2)) are combined with poly-(DL-lactide) to
      form a composite. The main properties studied are the ion release rates of
      biologically important ions (soluble SiO(2) and Ca(2+)) and the formation of bone
      mineral-like calcium phosphate (CaP) on the composite surface. These properties
      are studied by varying the quality, content and granule size of silica gel in the
      composite, and porosity of the polymer. The results indicate that release rates
      of SiO(2) and Ca(2+) depend mostly on the formed CaP layer, but in some extent
      also on the granule size of silicas and polymer porosity. The formation of the
      bone mineral-like CaP is suggested to be induced by a thin SiO(-) layer on the
      composite surface. However, due to absence of active SiO(2) or CaPSiO(2) granules
      on the outermost surface, the suitable nanoscale dimensions do not contribute the
      nucleation and growth and an extra source for calcium is needed instead. The
      result show also that all composites with varying amount of CaPSiO(2) (10-60 wt%)
      formed bone mineral-like CaP on their surfaces, which provides possibilities to
      optimise the mechanical properties of composites.

PMID- 14568435
TI  - Degradation of phospholipid polymer hydrogel by hydrogen peroxide aiming at
      insulin release device.
AB  - The purpose of this study is to ascertain the applicable possibility of H(2)O(2)
      degradable hydrogel for fabrication of insulin release system synchronized with
      the change in the glucose concentration in the medium. The hydrogel was prepared
      by using 2-methacryloyloxyethyl phosphorylcholine (MPC) and crosslinker. The
      favorable characteristic of the hydrogel was H(2)O(2) concentration responsive
      degradation. The H(2)O(2) was utilized and produced by enzymatic reaction between
      glucose oxidase and glucose. Poly(MPC) (PMPC) was easily degraded in H(2)O(2)
      aqueous solution, and the PMPC hydrogel was also degraded in H(2)O(2) aqueous
      solution. The degradation mechanism was considered to be main chain scission of
      PMPC. The degradation profile was evaluated by using weight swelling ratio and
      volume swelling ratio. The weight swelling ratio of PMPC hydrogel firstly
      increased due to the reduction of crosslink density, then the ratio decreased to
      zero (complete degradation). The degradation profile was proportional to the
      H(2)O(2) concentration. Furthermore, volume swelling ratio also increased, and
      complex elastic modulus decreased with degradation in H(2)O(2) aqueous solution.
      These results indicated that the hydrogel was degraded by hydroxy and/or
      hydroperoxy radicals which was produced by H(2)O(2), the crosslink density and
      mechanical property decreased. The release profile from the hydrogel was
      estimated by using lipid microsphere (LM) as an insulin model. The LM was
      released with the degradation of PMPC hydrogel. Taking these results into
      account, the PMPC hydrogel was available for H(2)O(2) degradable hydrogel for
      synchronization with glucose concentration by using enzymatic reaction.

PMID- 14568436
TI  - In vitro hemocompatibility studies of drug-loaded poly-(L-lactic acid) fibers.
AB  - Our objective was to evaluate the hemocompatibility of biodegradable stent
      fibers, employing a closed-loop circulation system filled with human blood. We
      also investigated the effects of the anti-inflammatory and anti-proliferative
      drugs curcumin and paclitaxel, incorporated into stent fibers. Fresh whole blood
      was circulated in four parallel closed-loop systems: the empty tube circuit
      (control) and tubes containing either a PLLA fiber coil (PLLA), a curcumin-loaded
      PLLA coil (C-PLLA) or a paclitaxel-loaded PLLA coil (P-PLLA). The influence of
      PLLA fiber, alone or loaded with drug incorporated during melt-extrusion, on
      leukocyte and platelet adhesion and activation was determined by flow cytometry.
      The effects of blood flow and fiber properties on cell deposition were assessed
      by scanning electron microscopy (SEM). The flow cytometry results clearly
      demonstrated that PLLA triggers blood cell activation at the site of deployment,
      as shown by increases in CD11b, CD62P and leukocyte-platelet aggregates, compared
      to controls. Curcumin and paclitaxel treatments both significantly reduced
      leukocyte and platelet activation and adhesion to PLLA fibers, as shown by flow
      cytometry and SEM. Activated leukocytes and platelets revealed significantly
      lower CD11b and CD62P receptor binding for C-PLLA compared with PLLA alone, and
      slightly lower for P-PLLA. Reductions in platelet-leukocyte aggregates were
      observed as well. In addition, there was less leukocyte and platelet adhesion to
      C-PLLA, compared with PLLA fiber controls, as shown by SEM. A continuous linear
      thrombus, composed of platelets, leukocytes, red blood cells and fibrin was
      occasionally detected along the line of tangency between the coil and the tube
      wall. Flow separation and eddying, proximal and distal to the line of tangency of
      coil and tube, is thought to contribute to this deposit. Curcumin was more
      effective than paclitaxel in reducing leukocyte and platelet activation and
      adhesion to PLLA stent fibers in this setting. However there was evidence of
      paclitaxel degeneration during melt extrusion that may have inhibited its
      effectiveness. Incorporation of the anti-inflammatory and anti-proliferative drug
      curcumin into bioresorbable stent fibers is proposed to prevent thrombosis and in
      stent restenosis.

PMID- 14568437
TI  - Development of self-etching primer comprised of methacrylamide, N-methacryloyl
      glycine.
AB  - In order to develop a more effective self-etching primer, it is helpful to
      understand how a functional monomer conditions the surface of the teeth.In this
      study, the reactivity by the carboxylic acid in the N-methacryloyl glycine
      (NMGly) on the calcium phosphate in hydroxyapatite or dentin was studied. The
      efficacy of the NMGly as a functional monomer for a self-etching primer was then
      examined. Applying NMGly to both the enamel and dentin resulted in an increase in
      the bond strength of resin, since the carboxylic acid in the NMGly decalcified
      the calcium phosphate in the hydroxyapatite and dentin. The bond strength to
      dentin achieved was higher than with the enamel. This difference was most likely
      due to different enamel and dentin adhesion mechanisms.

PMID- 14568438
TI  - Crack blunting, crack bridging and resistance-curve fracture mechanics in dentin:
      effect of hydration.
AB  - Few studies have focused on a description of the fracture toughness properties of
      dentin in terms of resistance-curve (R-curve) behavior, i.e., fracture resistance
      increasing with crack extension, particularly in light of the relevant toughening
      mechanisms involved. Accordingly, in the present study, fracture mechanics based
      experiments were conducted on elephant dentin in order to determine such R
      curves, to identify the salient toughening mechanisms and to discern how
      hydration may affect their potency. Crack bridging by uncracked ligaments,
      observed directly by microscopy and X-ray tomography, was identified as a major
      toughening mechanism, with further experimental evidence provided by compliance
      based experiments. In addition, with hydration, dentin was observed to display
      significant crack blunting leading to a higher overall fracture resistance than
      in the dehydrated material. The results of this work are deemed to be of
      importance from the perspective of modeling the fracture behavior of dentin and
      in predicting its failure in vivo.

PMID- 14568439
TI  - Predicting performance from functional imaging data: methods matter.
AB  - In the standard approach to functional imaging studies, brain-behavior
      relationships are studied by contrasting data obtained during different
      behavioral states. It is generally assumed that relative change yields meaningful
      data about relevant brain processes, and that the magnitude of the change
      reflects the extent of a region's involvement in the behavior being studied. The
      present study takes a different approach by asking the question, Can functional
      imaging data predict performance? Regional cerebral blood flow was measured using
      positron emission tomography in a group of 13 right-handed, normal volunteers
      during speech production and quiet baseline. A number of methodological
      assumptions were addressed by examining the relationships between different
      imaging measures derived from the same raw data and performance on the speech
      task. The results demonstrate that several common assumptions are not necessarily
      true. First, although measures based on "activated" scans alone had predictive
      value with respect to speech rate, measures based on contrasts between "baseline"
      and "activated" states did not. This was true regardless of whether the contrast
      was based on subtraction or covariance analyses. Second, while many regions
      demonstrated large signal increases during speech, speech rate could be predicted
      by a linear combination of data from two regions, neither of which had the
      highest "activation" peak, and one of which had a negative relationship with
      performance. The results demonstrate that contrasting experimental conditions do
      not necessarily isolate or enhance brain activity related to performance, and
      that the current assumptions about activation in functional imaging need to be
      reconsidered.

PMID- 14568441
TI  - Automatic change detection in multimodal serial MRI: application to multiple
      sclerosis lesion evolution.
AB  - The automatic analysis of subtle changes between MRI scans is an important tool
      for assessing disease evolution over time. Manual labeling of evolutions in 3D
      data sets is tedious and error prone. Automatic change detection, however,
      remains a challenging image processing problem. A variety of MRI artifacts
      introduce a wide range of unrepresentative changes between images, making
      standard change detection methods unreliable. In this study we describe an
      automatic image processing system that addresses these issues. Registration
      errors and undesired anatomical deformations are compensated using a versatile
      multiresolution deformable image matching method that preserves significant
      changes at a given scale. A nonlinear intensity normalization method is
      associated with statistical hypothesis test methods to provide reliable change
      detection. Multimodal data is optionally exploited to reduce the false detection
      rate. The performance of the system was evaluated on a large database of 3D
      multimodal, MR images of patients suffering from relapsing remitting multiple
      sclerosis (MS). The method was assessed using receiver operating characteristics
      (ROC) analysis, and validated in a protocol involving two neurologists. The
      automatic system outperforms the human expert, detecting many lesion evolutions
      that are missed by the expert, including small, subtle changes.

PMID- 14568440
TI  - Multivariate analysis of neuronal interactions in the generalized partial least
      squares framework: simulations and empirical studies.
AB  - Identification of spatiotemporal interactions within/between neuron populations
      is critical for detection and characterization of large-scale neuronal
      interactions underlying perception, cognition, and behavior. Univariate analysis
      has been employed successfully in many neuroimaging studies. However, univariate
      analysis does not explicitly test for interactions between distributed areas of
      activity and is not sensitive to distributed responses across the brain.
      Multivariate analysis can explicitly test for multiple statistical models,
      including the designed paradigm, and allows for spatial and temporal model
      detection. Here, we investigate multivariate analysis approaches that take into
      consideration the 4D (time and space) covariance structure of the data. Principal
      component analysis (PCA) and independent component analysis (ICA) are two popular
      multivariate approaches with distinct mathematical constraints. Common
      difficulties in using these two different decompositions include the following:
      classification of the revealed components (task-related signal versus noise),
      overall signal-to-noise sensitivity, and the relatively low computational
      efficiency (multivariate analysis requires the entire raw data set and more time
      for model identification analysis). Using both Monte Carlo simulations and
      empirical data, we derived and tested the generalized partial least squares
      (gPLS) framework, which can incorporate both PCA and ICA decompositions with
      computational efficiency. The gPLS method explicitly incorporates the
      experimental design to simplify the identification of characteristic
      spatiotemporal patterns. We performed parametric modeling studies of a blocked
      design experiment under various conditions, including background noise
      distribution, sampling rate, and hemodynamic response delay. We used a randomized
      grouping approach to manipulate the degrees of freedom of PCA and ICA in gPLS to
      characterize both paradigm coherent and transient brain responses. Simulation
      data suggest that in the gPLS framework, PCA mostly outperforms ICA as measured
      by the receiver operating curves (ROCs) in SNR from 0.01 to 100, the hemodynamic
      response delays from 0 to 3 TR in fMRI, background noise models of Guassian, sub
      Gaussian, and super-Gaussian distributions and the number of observations from 5,
      10, to 20 in each block of a six-block experiment. Further, due to selective
      averaging, the gPLS method performs robustly in low signal-to-noise ratio (<1)
      experiments. We also tested PCA and ICA using PLS in a simulated event-related
      fMRI data to show their similar detection. Finally, we tested our gPLS approach
      on empirical fMRI motor data. Using the randomized grouping method, we are able
      to identify both transient responses and consistent paradigm/model coherent
      components in the 10-epoch block design motor fMRI experiment. Overall, studies
      of synthetic and empirical data suggest that PLS analysis, using PCA
      decomposition, provides a stable and powerful tool for exploration of
      fMRI/behavior data.

PMID- 14568442
TI  - Temporal dynamics of linguistic processes are reorganized in aphasics' cortex: an
      EEG mapping study.
AB  - Brain lesions are known to elicit reorganization of function in representational
      cortex. Using linguistic function as an example, we show that (a) injury-related
      reorganization may also be observed in language-related cortex and (b) this
      reorganization not only appears in cortical space but also in the dynamic flow of
      activity. The present study investigated cortical reorganization in a group of 10
      nonfluent aphasics who demonstrated partial recovery of linguistic functions.
      Compared with controls, linguistic functions were organized in an atypical
      manner, both in terms of spatial structures involved and in the time course of
      the linguistic processes, from word reading to late stages of word encoding in
      working memory. For this purpose, event-related potentials were recorded in a two
      stimulus design comprising phonological and semantic tasks. Subjects were asked
      to judge whether two words, separated by a 2-s interval, rhymed (phonological
      task) or were semantically associated. During word reading of the phonological
      task, controls showed negativity/activation over occipital sites, whereas
      patients displayed negativity at left-medial orbitofrontal locations anterior to
      the common sites of lesion. During the subsequent 2-s interval associated with
      word encoding, the two groups showed a reversed pattern: significant left-right
      anterior asymmetry prevailed in controls, whereas lateralization was absent in
      patients. Aphasics displayed maximum positivity/inhibition over the left frontal
      regions, at the typical site of lesion. Compared with controls, patients
      exhibited significant disinhibition (decreased positivity) of right frontal areas
      and greater activation of left temporal sites. These results suggest that the
      concept of language plasticity should include, in addition to spatial aspects of
      linguistic reorganization, the reorganized temporal dynamics associated with
      recovery of impaired functions.

PMID- 14568443
TI  - Changes in hippocampal volume and shape across time distinguish dementia of the
      Alzheimer type from healthy aging.
AB  - Rates of hippocampal volume loss have been shown to distinguish subjects with
      dementia of the Alzheimer type (DAT) from nondemented controls. In this study, we
      obtained magnetic resonance scans in 18 subjects with very mild DAT (CDR 0.5) and
      26 age-matched nondemented controls (CDR 0) 2 years apart. Large-deformation high
      dimensional brain mapping was used to quantify and compare changes in hippocampal
      shape as well as volume in the two groups of subjects. Hippocampal volume loss
      over time was significantly greater in the CDR 0.5 subjects (left = 8.3%, right =
      10.2%) than in the CDR 0 subjects (left = 4.0%, right = 5.5%) (ANOVA, F = 7.81, P
      = 0.0078). We used singular-value decomposition and logistic regression models to
      quantify hippocampal shape change across time within individuals, and this shape
      change in the CDR 0.5 and CDR 0 subjects was found to be significantly different
      (Wilks's lambda, P = 0.014). Further, at baseline, CDR 0.5 subjects, in
      comparison to CDR 0 subjects, showed inward deformation over 38% of the
      hippocampal surface; after 2 years this difference grew to 47%. Also, within the
      CDR 0 subjects, shape change between baseline and follow-up was largely confined
      to the head of the hippocampus and subiculum, while in the CDR 0.5 subjects,
      shape change involved the lateral body of the hippocampus as well as the head
      region and subiculum. These results suggest that different patterns of
      hippocampal shape change in time as well as different rates of hippocampal volume
      loss distinguish very mild DAT from healthy aging.

PMID- 14568444
TI  - Functional MRI in neonates using neonatal head coil and MR compatible incubator.
AB  - Structural and functional magnetic resonance imaging of the newborn brain is a
      complex and challenging task. Term and preterm neonates require a controlled
      microenvironment and close monitoring during the MRI study to maintain
      respiratory and cardiovascular functions, body temperature, and fluid and
      electrolyte homeostasis. In addition, to minimize motion artifacts, most neonates
      also need to be sedated, which carries the risk of respiratory depression
      compromising the neonate's ability to maintain appropriate ventilation and
      oxygenation during the procedure. Finally, because of their small head size, the
      use of the standard MR head coils results in suboptimal picture quality in the
      neonate. Thus, these limitations affect our ability to obtain both high quality
      structural and functional MRI studies. To overcome these difficulties, we have
      utilized an MR compatible incubator with a built-in radiofrequency head coil
      optimized for the neonatal brain volume. In this study we demonstrate that
      functional MRI and high-resolution structural MRI of the newborn brain can be
      achieved with this novel design. The use of this equipment offers potential for
      studying the development of the preterm and term neonatal brain and obtaining
      state-of-the-art, high-resolution structural and functional imaging in this most
      vulnerable patient population.

PMID- 14568445
TI  - Evaluation of the dual route theory of reading: a metanalysis of 35 neuroimaging
      studies.
AB  - Numerous studies concerned with cerebral structures underlying word reading have
      been published during the last decade. A few controversies, however, together
      with methodological or theoretical discrepancies between laboratories, still
      contribute to blurring the overall view of advances effected in neuroimaging.
      Carried out within the dual route of reading framework, the aim of this
      metanalysis was to provide an objective picture of these advances. To achieve
      this, we used an automated analysis method based on the inventory of activation
      peaks issued from word or pseudoword reading contrasts of 35 published
      neuroimaging studies. A first result of this metanalysis was that no cluster of
      activations has been found more recruited by word than pseudoword reading,
      implying that the first steps of word access may be common to word and word-like
      stimuli and would take place within a left occipitotemporal region (previously
      referred to as the Visual Word Form Area-VWFA) situated in the ventral route, at
      the junction between inferior temporal and fusiform gyri. The results also
      indicated the existence of brain regions predominantly involved in one of the two
      routes to access word. The graphophonological conversion seems indeed to rely on
      left lateralized brain structures such as superior temporal areas, supramarginal
      gyrus, and the opercular part of the inferior frontal gyrus, these last two
      regions reflecting a greater load in working memory during such an access. The
      lexicosemantic route is thought to arise from the coactivation of the VWFA and
      semantic areas. These semantic areas would encompass a basal inferior temporal
      area, the posterior part of the middle temporal gyrus, and the triangular part of
      inferior frontal gyrus. These results confirm the suitability of the dual route
      framework to account for activations observed in nonpathological subjects while
      they read.

PMID- 14568446
TI  - fMRI of emotional responses to odors: influence of hedonic valence and judgment,
      handedness, and gender.
AB  - Previous positron emission tomography studies of right-handed individuals show
      that the left orbitofrontal cortex is dominant during emotional processing of
      odors. We collected functional magnetic resonance imaging data from 28 subjects
      to study this network as a function of odor hedonic valence (pleasant vs.
      unpleasant), active hedonic judgments versus passive sensation of hedonically
      charged odors, handedness, and gender. Two functional runs were performed, with
      pleasant and unpleasant odors presented in different epochs. In the first run,
      subjects passively smelled odorants, whereas in the second run they rated degree
      of odor pleasantness or unpleasantness by using a "finger-span" technique that
      simulated a visual rating scale. Electrodermal and plethysmography responses were
      simultaneously recorded to control for covert, physiological manifestations of
      the emotional response. The piriform-amygdala area and ventral insula were
      activated more for unpleasant than pleasant odors. More extreme ratings were also
      associated with higher electrodermal amplitude, suggesting that activation
      stemmed more from emotional or hedonic intensity than valence, and that
      unpleasant odors induced more arousal than pleasant odors. Unpleasant odors
      activated the left ventral insula in right-handers and the right ventral insula
      in left-handers, suggesting lateralized processing of emotional odors as a
      function of handedness. Active decisions about odor pleasantness induced specific
      left orbitofrontal cortex activation, implicating the role of this area in the
      conscious assessment of the emotional quality of odors. Finally, left
      orbitofrontal cortex was more active in women than men, potentially in relation
      to women's well-documented advantage in odor identification.

PMID- 14568447
TI  - Functional neuroanatomy of auditory mismatch processing: an event-related fMRI
      study of duration-deviant oddballs.
AB  - This study was designed to identify the neural networks underlying automatic
      auditory deviance detection in 10 healthy subjects using functional magnetic
      resonance imaging. We measured blood oxygenation level-dependent contrasts
      derived from the comparison of blocks of stimuli presented as a series of
      standard tones (50 ms duration) alone versus blocks that contained rare duration
      deviant tones (100 ms) that were interspersed among a series of frequent standard
      tones while subjects were watching a silent movie. Possible effects of scanner
      noise were assessed by a "no tone" condition. In line with previous positron
      emission tomography and EEG source modeling studies, we found temporal lobe and
      prefrontal cortical activation that was associated with auditory duration
      mismatch processing. Data were also analyzed employing an event-related
      hemodynamic response model, which confirmed activation in response to duration
      deviant tones bilaterally in the superior temporal gyrus and prefrontally in the
      right inferior and middle frontal gyri. In line with previous
      electrophysiological reports, mismatch activation of these brain regions was
      significantly correlated with age. These findings suggest a close relationship of
      the event-related hemodynamic response pattern with the corresponding
      electrophysiological activity underlying the event-related "mismatch negativity"
      potential, a putative measure of auditory sensory memory.

PMID- 14568448
TI  - Neural development of selective attention and response inhibition.
AB  - Brain activation differences between 12 children (9- to 12-year-olds) and 12
      adults (20- to 30-year-olds) were examined on two cognitive tasks during
      functional magnetic resonance imaging (fMRI). Spatial selective attention was
      measured with the visual search for a conjunction target (red triangle) in a
      field of distracters and response inhibition was measured with a go no-go task.
      There were small developmental differences in the selective attention task, with
      children showing greater activation than adults in the anterior cingulate and
      thalamus. There were large developmental differences in the response inhibition
      task, with children showing greater activation than adults in a fronto-striatal
      network including middle cingulate, medial frontal gyrus, medial aspects of
      bilateral superior frontal gyrus, and the caudate nucleus on the left. Children
      also showed greater bilateral activation for the response inhibition task in
      posterior cingulate, thalamus and the hippocampo-amygdaloid region. The extensive
      developmental differences on the response inhibition task are consistent with the
      prolonged maturation of the fronto-striatal network.

PMID- 14568449
TI  - Electrical impedance tomography of human brain function using reconstruction
      algorithms based on the finite element method.
AB  - Electrical impedance tomography (EIT) is a recently developed technique which
      enables the internal conductivity of an object to be imaged using rings of
      external electrodes. In a recent study, EIT during cortical evoked responses
      showed encouraging changes in the raw impedance measurements, but reconstructed
      images were noisy. A simplified reconstruction algorithm was used which modelled
      the head as a homogeneous sphere. In the current study, the development and
      validation of an improved reconstruction algorithm are described in which
      realistic geometry and conductivity distributions have been incorporated using
      the finite element method. Data from computer simulations and spherical or head
      shaped saline-filled tank phantoms, in which the skull was represented by a
      concentric shell of plaster of Paris or a real human skull, have been
      reconstructed into images. There were significant improvements in image quality
      as a result of the incorporation of accurate geometry and extracerebral layers in
      the reconstruction algorithm. Image quality, assessed by blinded subjective
      expert observers, also improved significantly when data from the previous evoked
      response study were reanalysed with the new algorithm. In preliminary images
      collected during epileptic seizures, the new algorithm generated EIT conductivity
      changes which were consistent with the electrographic ictal activity.
      Incorporation of realistic geometry and conductivity into the reconstruction
      algorithm significantly improves the quality of EIT images and lends
      encouragement to the belief that EIT may provide a low-cost, portable functional
      neuroimaging system in the foreseeable future.

PMID- 14568450
TI  - Single-trial variability in early visual neuromagnetic responses: an explorative
      study based on the regional activation contributing to the N70m peak.
AB  - Cortical activity evoked by repeated identical sensory stimulation is extremely
      variable. The source of this variability is often assigned to "random ongoing
      background activity" which is considered to be irrelevant to the processing of
      the stimuli and can therefore be eliminated by ensemble averaging. In this work,
      we studied the single-trial variability in neuromagnetic responses elicited by
      circular checkerboard pattern stimuli with radii of 1.8 degrees, 3.7 degrees, and
      4.5 degrees. For most of the MEG sensors over the occipital areas, the averaged
      signal showed a clear early (N70m) response following the stimulus onset and this
      response was modulated by the checkerboard size. A data-driven spatial filter was
      used to extract one of the many possible composite time courses of single-trial
      activity corresponding to the complex of N70m generators. Pattern analysis
      principles were then employed to analyze, classify, and handle the extracted
      temporal patterns. We explored whether these patterns correspond to distinct
      response modes, which could characterize the evoked response better than the
      averaged signal and over an extended range of latencies around N70m. A novel
      scheme for detecting and organizing the structure in single-trial recordings was
      utilized. This served as a basis for comparisons between runs with different
      checkerboard sizes and provided a causal interpretation of variability in terms
      of regional dynamics, including the relatively weak activation in primary visual
      cortex. At the level of single trial activity, the polymorphic response to a
      simple stimulus is generated by a coupling of polymodal areas and cooperative
      activity in striate and extrastriate areas. Our results suggest a state-dependent
      response with a wide range of characteristic time scales and indicate the ongoing
      activity as a marker of the responsiveness state.

PMID- 14568451
TI  - Time-dependent neural activations related to recognition of people's names in
      emotional and neutral face-name associative learning: an fMRI study.
AB  - Previous data have indicated that the left anterior temporal lobe contributes to
      the retrieval of familiar people's names, and that the extended network including
      the bilateral anterior temporal lobe plays an important role in the retrieval of
      newly learned people's names. However, there has been no direct evidence for time
      dependent change in brain activation in face-name associations. In addition,
      previous studies have demonstrated that emotional information such as emotional
      faces may contribute to the organization of long-lasting episodic memory. In the
      present study, we investigated the activations related to the recognition of
      people's names in the context of emotional and neutral face-name associative
      learning. Before fMRI scanning, subjects learned face-name associations that
      included emotionally positive and neutral facial expressions. In immediate (5 min
      later) and delayed (2 weeks later) recognition with fMRI scanning, subjects were
      presented with studied faces with two names, and were asked to choose the correct
      associative name learned previously. Recognition-related activations were
      identified in the anterior part of bilateral temporal lobe for immediate
      recognition and only in the left temporal lobe for delayed recognition. Further
      analysis confirmed the time-dependent change in activation of the right anterior
      temporal lobe. Activation related to the processing of faces with positive
      expressions were observed in the left periamygdaloid area and temporal pole,
      although emotional information did not have an influence on task performance in
      this study. These findings suggest that the neural network involving the
      bilateral temporal lobe contributes to the retrieval of newly learned people's
      names, and that the left temporal lobe has a crucial and stable role in retrieval
      of people's names from faces, whereas the role of the right temporal lobe in
      retrieval of people's names may decrease with the time course.

PMID- 14568452
TI  - Morphological study of the healthy human oculomotor nerve by atomic force
      microscopy.
AB  - This study concerns an investigation of oculomotor nerves via imaging semithin
      sections with an atomic force microscope (AFM). The study used 10 oculomotor
      nerves removed from individuals aged between 40 and 60 years old at time of
      death. We adopted semithin sections for our AFM studies to extract topographical
      data of the fibers of this nerve. Both light microscope and electron microscope
      images of the same samples were employed to augment our capabilities for
      orientation in the AFM analyses. Transverse sections of the oculomotor nerve,
      imaged via AFM, show clearly identifiable ring-like nerve fibers with the
      myelinated axons. The samples were simultaneously characterized by error signal
      mode and lateral force microscopy. These AFM-related techniques revealed no
      information concerning friction force and elasticity due to the presence of the
      embedding material (epoxy resin), but showed the myelinated nerve fibers with
      ring-like structures corresponding to the myelin sheaths. These are the first AFM
      images of physiological human oculomotor nerves, containing clear three
      dimensional representations of these samples.

PMID- 14568453
TI  - Assessing brain activity through spatial Bayesian variable selection.
AB  - Statistical parametric mapping (SPM), relying on the general linear model and
      classical hypothesis testing, is a benchmark tool for assessing human brain
      activity using data from fMRI experiments. Friston et al. discuss some
      limitations of this frequentist approach and point out promising Bayesian
      perspectives. In particular, a Bayesian formulation allows explicit modeling and
      estimation of activation probabilities. In this study, we directly address this
      issue and develop a new regression based approach using spatial Bayesian variable
      selection. Our method has several advantages. First, spatial correlation is
      directly modeled for activation probabilities and indirectly for activation
      amplitudes. As a consequence, there is no need for spatial adjustment in a
      postprocessing step. Second, anatomical prior information, such as the
      distribution of grey matter or expert knowledge, can be included as part of the
      model. Third, the method has superior edge-preservation properties as well as
      being fast to compute. When applied to data from a simple visual experiment, the
      results demonstrate improved sensitivity for detecting activated cortical areas
      and for better preserving details of activated structures.

PMID- 14568454
TI  - Dynamics of gamma-band activity in human magnetoencephalogram during auditory
      pattern working memory.
AB  - Both electrophysiological research in animals and human brain imaging studies
      have suggested that, similar to the visual system, separate cortical ventral
      "what" and dorsal "where" processing streams may also exist in the auditory
      domain. Recently we have shown enhanced gamma-band activity (GBA) over posterior
      parietal cortex belonging to the putative auditory dorsal pathway during a sound
      location working memory task. Using a similar methodological approach, the
      present study assessed whether GBA would be increased over auditory ventral
      stream areas during an auditory pattern memory task. Whole-head
      magnetoencephalogram was recorded from N = 12 subjects while they performed a
      working memory task requiring same-different judgments about pairs of syllables
      S1 and S2 presented with 0.8-s delays. S1 and S2 could differ either in voice
      onset time or in formant structure. This was compared with a control task
      involving the detection of possible spatial displacements in the background sound
      presented instead of S2. Under the memory condition, induced GBA was enhanced
      over left inferior frontal/anterior temporal regions during the delay phase and
      in response to S2 and over prefrontal cortex at the end of the delay period.
      gamma-Band coherence between left frontotemporal and prefrontal sensors was
      increased throughout the delay period of the memory task. In summary, the
      memorization of syllables was associated with synchronously oscillating networks
      both in frontotemporal cortex, supporting a role of these areas as parts of the
      putative auditory ventral stream, and in prefrontal, possible executive regions.
      Moreover, corticocortical connectivity was increased between these structures.

PMID- 14568455
TI  - Noninvasive measurement of regional cerebral blood flow and regional cerebral
      blood volume by near-infrared spectroscopy and indocyanine green dye dilution.
AB  - To find a suitable method for measuring regional cerebral blood flow (rCBF)
      rapidly at the bedside is still a matter of investigation. The purpose here was
      to develop a noninvasive method for bedside rCBF measurement and to validate it
      with a standard method such as perfusion-weighted magnetic resonance imaging
      (MRI). In 11 healthy volunteers 44 measurements with near-infrared spectroscopy
      (NIRS) and perfusion-weighted MRI without and with a mean continuous positive
      airway pressure (CPAP) of 10 mbar were carried out. Four (NIRS) optodes were
      placed bilaterally on the forehead and 25 mg indocyanine green (ICG) was
      injected. New algorithms were developed to calculate rCBFNIRS and rCBVNIRS. In 6
      volunteers data analysis was successful. No complications associated with the
      method were observed. During CPAP breathing rCBFNIRS decreased from 18.5 + 6.9
      16.1 + 6.2 ml/100 g/min (P = 0.034). Mean values for rCBFMRI decreased from 256
      +/- 90 to 216 +/- 62 ml/100 g/min (P = 0.012). Bland and Altman plots showed that
      the differences did not vary in any systematic way over the range of rCBF or rCBV
      values assessed and 100% of differences were within the interval mean +/- 2 SD of
      differences. Limits of agreement (mean +/- 2 SD) were +/- 76.4 ml/100 g/min for
      rCBF and +/- 15.6 ml/100 g for rCBV. The NIRS ICG dye dilution technique is a
      promising method for serial noninvasive bedside CBF measurements. The preliminary
      data indicate that measurements are in agreement with values obtained by
      perfusion-weighted MRI.

PMID- 14568456
TI  - Involvement of multiple functionally distinct cerebellar regions in visual
      discrimination: a human functional imaging study.
AB  - We investigated the contribution of the human cerebellum to cerebral function
      during visual discrimination using PET and fMRI. The cognitive task was a
      successive discrimination of shades of brown with a parametric variation of the
      stimulus presentation rate and a constant task difficulty. The successive color
      discrimination task was contrasted to a dimming detection control task, with
      identical retinal input but with double the number of motor responses. Three sets
      of activated cerebellar and cerebral regions were observed: rate-dependent and
      rate-independent color discrimination networks and a motor-and-detection network.
      The rate-dependent color discrimination network included both an anterior and a
      posterior activation site in lobule-VI of the two lateral cerebellar hemispheres,
      whereas the rate-independent network involved a bilateral activation site in
      lateral Crus-I. Cerebellar sites of the motor-and-detection network were located
      in medial lobule-V bilaterally, in the vermis, and in posterior left Crus-I and
      right Crus-II. An additional fMRI study was performed to control for differences
      in motor output and response timing between the tasks. In this control study, the
      cerebellar activation sites of the rate-dependent and rate-independent color
      discrimination networks remained unaltered. The motor-and-detection network
      included cerebellar activations in posterior left Crus-I and right Crus-II, but
      none in lobule-V or the vermis. Thus, cerebellar activation sites of the motor
      and-detection network could be subdivided into those related to a motor network
      and those belonging to a dimming detection network. We conclude that successive
      color discrimination activates multiple, functionally distinct cerebellar
      regions.

PMID- 14568457
TI  - Brain processing of visual sexual stimuli in healthy men: a functional magnetic
      resonance imaging study.
AB  - The brain plays a central role in sexual motivation. To identify cerebral areas
      whose activation was correlated with sexual desire, eight healthy male volunteers
      were studied with functional magnetic resonance imaging (fMRI). Visual stimuli
      were sexually stimulating photographs (S condition) and emotionally neutral
      photographs (N condition). Subjective responses pertaining to sexual desire were
      recorded after each condition. To image the entire brain, separate runs focused
      on the upper and the lower parts of the brain. Statistical Parametric Mapping was
      used for data analysis. Subjective ratings confirmed that sexual pictures
      effectively induced sexual arousal. In the S condition compared to the N
      condition, a group analysis conducted on the upper part of the brain demonstrated
      an increased signal in the parietal lobes (superior parietal lobules, left
      intraparietal sulcus, left inferior parietal lobule, and right postcentral
      gyrus), the right parietooccipital sulcus, the left superior occipital gyrus, and
      the precentral gyri. In addition, a decreased signal was recorded in the right
      posterior cingulate gyrus and the left precuneus. In individual analyses
      conducted on the lower part of the brain, an increased signal was found in the
      right and/or left middle occipital gyrus in seven subjects, and in the right
      and/or left fusiform gyrus in six subjects. In conclusion, fMRI allows to
      identify brain responses to visual sexual stimuli. Among activated regions in the
      S condition, parietal areas are known to be involved in attentional processes
      directed toward motivationally relevant stimuli, while frontal premotor areas
      have been implicated in motor preparation and motor imagery. Further work is
      needed to identify those specific features of the neural responses that
      distinguish sexual desire from other emotional and motivational states.

PMID- 14568458
TI  - How to correct susceptibility distortions in spin-echo echo-planar images:
      application to diffusion tensor imaging.
AB  - Diffusion tensor imaging is often performed by acquiring a series of diffusion
      weighted spin-echo echo-planar images with different direction diffusion
      gradients. A problem of echo-planar images is the geometrical distortions that
      obtain near junctions between tissues of differing magnetic susceptibility. This
      results in distorted diffusion-tensor maps. To resolve this we suggest acquiring
      two images for each diffusion gradient; one with bottom-up and one with top-down
      traversal of k-space in the phase-encode direction. This achieves the
      simultaneous goals of providing information on the underlying displacement field
      and intensity maps with adequate spatial sampling density even in distorted
      areas. The resulting DT maps exhibit considerably higher geometric fidelity, as
      assessed by comparison to an image volume acquired using a conventional 3D MR
      technique.

PMID- 14568459
TI  - Abnormal processing of speech during oddball target detection in schizophrenia.
AB  - Healthy subjects show increased activation in left temporal lobe regions in
      response to speech sounds compared to complex nonspeech sounds. Abnormal
      lateralization of speech-processing regions in the temporal lobes has been
      posited to be a cardinal feature of schizophrenia. Event-related fMRI was used to
      test the hypothesis that schizophrenic patients would show an abnormal pattern of
      hemispheric lateralization when detecting speech compared with complex nonspeech
      sounds in an auditory oddball target-detection task. We predicted that
      differential activation for speech in the vicinity of the superior temporal
      sulcus would be greater in schizophrenic patients than in healthy subjects in the
      right hemisphere, but less in patients than in healthy subjects in the left
      hemisphere. Fourteen patients with schizophrenia (selected from an outpatient
      population, 2 females, 12 males, mean age 35.1 years) and 29 healthy subjects (8
      females, 21 males, mean age 29.3 years) were scanned while they performed an
      auditory oddball task in which the oddball stimuli were either speech sounds or
      complex nonspeech sounds. Compared to controls, individuals with schizophrenia
      showed greater differential activation between speech and nonspeech in right
      temporal cortex, left superior frontal cortex, and the left temporal-parietal
      junction. The magnitude of the difference in the left temporal parietal junction
      was significantly correlated with severity of disorganized thinking. This study
      supports the hypothesis that aberrant functional lateralization of speech
      processing is an underlying feature of schizophrenia and suggests the magnitude
      of the disturbance in speech-processing circuits may be associated with severity
      of disorganized thinking.

PMID- 14568460
TI  - Effects of attenuation correction and reconstruction method on PET activation
      studies.
AB  - The outcome of Statistical Parametric Mapping (SPM) analyses of PET activation
      studies depends among others, on the quality of reconstructed data. In general,
      filtered back-projection (FBP) is used for reconstruction in PET activation
      studies. There is, however, increasing interest in iterative reconstruction
      algorithms such as ordered subset expectation maximization (OSEM) algorithms. The
      aim of the present study was to investigate the effects of reconstruction
      techniques and attenuation correction (AC) on the detection of activation foci
      following statistical analysis with SPM. First, a replicate study was performed
      to assess the effects of the reconstruction method on pixel variance. Second, a
      phantom study was performed to evaluate the influence of both locations of an
      activated area and applied reconstruction method on SPM outcome. A volumetric
      method was used to compute the number of false positive voxels for all
      reconstructions. In addition, average t values within activation foci and for
      false positive voxels were calculated. For the assessment of the effects of
      reconstruction on clinical data, a group of 11 patients was studied. For all
      reconstructions SPM maps were created and compared. Both the clinical and the
      phantom data showed that use of iterative reconstruction methods reduced false
      positive results, while showing similar SPM results within activated areas as
      FBP. Reconstruction of data without attenuation correction reduced noise for FBP
      only, but did not affect the quality of SPM results for OSEM. It is concluded
      that OSEM is a good alternative for FBP reconstructions providing SPM results
      with less noise.

PMID- 14568461
TI  - Differential effects of stimulus intensity on peripheral and neuromagnetic
      cortical responses to median nerve stimulation.
AB  - To study the differential effects of tactile stimulus intensity on cortical and
      peripheral responses, we measured neuromagnetic cortical responses, compound
      muscle action potentials (CMAP), sensory nerve action potentials (SNAP), and the
      subjective estimation of tactile magnitude to electric median nerve stimulation
      at the wrist in 13 male healthy adults. The sensory perception threshold (ST) for
      electric pulses at wrist skin was determined and then various levels of stimulus
      intensity (1 approximately 6 ST) were given to each subject. At 1 ST, only the
      P50m components of the primary somatosensory (SI) cortical responses were
      recorded. The second somatosensory (SII) cortical responses were saturated at 2
      ST, while the SI responses reached maximum at 3 ST equivalent to the subjective
      threshold intensity for "strong" tactility. The CMAP and SNAP were maximum at 4-5
      ST. At 2 ST, >70% of maximum SI responses were produced, whereas only <40% of
      maximum CMAP or SNAP responses were obtained. We concluded that the stimulus
      intensities for activating or saturating somatosensory cortical responses were
      lower than those for CMAP and SNAP. The differential intensity effects on
      cortical and peripheral responses suggest a polysynaptic organization underlying
      the central amplification for somatosensory cortical activation. The optimal
      intensity levels for producing maximum SI and SII responses were 3 and 2 ST,
      respectively. Compared with the SII, the SI plays a crucial role in the coding of
      the tactile stimulus intensity.

PMID- 14568462
TI  - Neural correlates of the complexity of rhythmic finger tapping.
AB  - Using functional magnetic resonance imaging (fMRI), we studied the neural
      correlates of the complexity of rhythmic finger tapping. Our experiments measured
      the brain activity of 13 subjects performing rhythmic tapping on a response box
      with multistable rhythms of 1 to 5 different interresponse intervals. From the
      button press response times, we constructed phase portraits where we identified
      the number of clusters of periodic points in a rhythm that corresponded to the
      number of different beats of the rhythm performed. We then constructed a
      statistical model for correlation analysis involving the following behavioral
      parameters: rate of tapping and number of beats in a rhythm. The tapping rate
      correlated with the brain activity in the ipsilateral pre/postcentral gyrus, and
      the number of beats (complexity) was correlated with activations in the primary
      motor cortex, supplementary motor area, basal ganglia, thalamus, and cerebellum.
      A region of interest (ROI) average analysis showed that the complexity of a
      rhythm had a differential correlation with the activity in these regions. The
      cerebellum and the thalamus showed increasing activity, and the basal ganglia
      showed decreasing activity with complexity of a rhythm. These results identify
      the areas involved in a rhythm generation and the modulation of brain activity
      with the complexity.

PMID- 14568463
TI  - Functional neuroanatomy of learned helplessness.
AB  - In the experiments reported here, female subjects were presented with reasoning
      tasks that changed from solvable to unsolvable, evoking "learned helplessness" or
      "loss of control" reactions in some subjects. Significant differences in slow
      cortical potential (SCP) changes were found between emotionally highly and lowly
      reactive subjects (grouped according to responses in postexperimental
      questionnaires) when processing unsolvable tasks. Cortical LORETA of SCP
      topographies and subsequent statistical nonparametric mapping (SnPM; analysis
      indicate clear reduction of anterior cingulate activity only with emotionally
      highly reactive subjects. In these subjects a region of the brain that is
      indispensable for goal-directed handling of tasks was switched off, whereas
      regions that are primarily engaged in processing the task stimuli were even more
      active during loss of control, although not at a statistically significant level.
      According to the anterior cingulate monitors the conflicts among brain regions
      and issues calls for further processing to the PFC that then guides behavior
      toward a goal. Learned helplessness might then be seen a state in which the
      function of the anterior cingulate is no longer maintained, perhaps due to the
      inhibitory influence of the amygdala possibly mediated via the brainstem
      dopaminergic ventral tegmental area.

PMID- 14568464
TI  - Effects of gender on blood flow correlates of naming concrete entities.
AB  - A cross-cohort PET analysis was performed in 62 normal subjects (31 men and 31
      women) to address the issue of whether men and women have different physiologic
      correlates of naming visually presented concrete entities. The subjects named
      nonunique concrete entities in one or more conceptual categories and also
      performed a face orientation decision task. A second analysis was performed in 24
      additional subjects to assess whether there were gender effects related to the
      face orientation decision task and to constrain the interpretation of the first
      analysis. Male subjects engaged the left inferotemporal region and several other
      left hemisphere regions more than female subjects did during visual naming. Areas
      showing more activity in female subjects included the right inferior frontal
      gyrus and right precentral cortex, regions that were less active in visual naming
      than in the face orientation decision task. In other words, the male subjects
      engaged the latter regions less or deactivated them more than female subjects.
      The results can be interpreted as showing a greater modulation of activity in
      both hemispheres for men compared to women. Although the gender effects we found
      are smaller than the task effects, they are not negligible for the purposes of
      performing and interpreting functional imaging studies.

PMID- 14568465
TI  - Functional activation using apparent diffusion coefficient-dependent contrast
      allows better spatial localization to the neuronal activity: evidence using
      diffusion tensor imaging and fiber tracking.
AB  - Recent studies suggested that functional activation using apparent diffusion
      coefficient (ADC) contrast can be used to detect synchronized functional MRI
      (fMRI) signal changes during brain activation. Such changes may reflect better
      spatial localization to the smaller vessels, which are closely coupled to the
      true neuronal activation. Since it is generally believed that there are neural
      pathways among neuronally relevant areas, methods that would allow clear
      delineation of such pathways could help validate the neuronal relevance of the
      activated functional areas. The development of diffusion tensor imaging (DTI) has
      shown promise in detailed nerve fiber tracking. In this report, DTI was adopted
      to track the fiber connections among the discrete areas determined using the ADC
      contrast, in an effort to confirm the neuronal origin of these activated areas.
      As a comparison, activated areas using blood oxygenation level-dependent (BOLD)
      contrast were also obtained. Our results showed that the areas determined by the
      ADC contrast consistently allowed better fiber tracking within, while the BOLD
      activated areas were more spatially diffused due to the smearing effect of brain
      vasculature, rendering the task of fiber tracking more difficult. This
      observation provides converging evidence that the activated areas using ADC
      contrast are more closely coupled to the neuronal activity than those using BOLD
      contrast.

PMID- 14568466
TI  - Functional connectivity: studying nonlinear, delayed interactions between BOLD
      signals.
AB  - Correlation analysis has been widely used in the study of functional connectivity
      based on fMRI data. It assumes that the relevant information about the
      interactions of brain regions is reflected by a linear relationship between the
      values of two signals at the same time. However, this hypothesis has not been
      thoroughly investigated yet. In this work, we study in depth the information
      shared by BOLD signals of pairs of brain regions. In particular, we assess the
      amount of nonlinear and/or nonsynchronous interactions present in data. This is
      achieved by testing models reflecting linear, synchronous interactions against
      more general models, encompassing nonlinear, nonsynchronous interactions. Many
      factors influencing measured BOLD signals are critical for the study of
      connectivity, such as paradigm-induced BOLD responses, preprocessing, motion
      artifacts, and geometrical distortions. Interactions are also influenced by the
      proximity of brain regions. The influence of all these factors is taken into
      account and the nature of the interactions is studied using various experimental
      conditions such that the conclusions reached are robust with respect to variation
      of these factors. After defining nonlinear and/or nonsynchronous interaction
      models in the framework of general linear models, statistical tests are performed
      on different fMRI data sets to infer the nature of the interactions. Finally, a
      new connectivity metric is proposed which takes these inferences into account. We
      find that BOLD signal interactions are statistically more significant when taking
      into account the history of the distant signal, i.e., the signal from the
      interacting region, than when using a model of linear instantaneous interaction.
      Moreover, about 75% of the interactions are symmetric, as assessed with the
      proposed connectivity metric. The history-dependent part of the coupling between
      brain regions can explain a high percentage of the variance in the data sets
      studied. As these results are robust with respect to various confounding factors,
      this work suggests that models used to study the functional connectivity between
      brain areas should in general take the BOLD signal history into account.

PMID- 14568467
TI  - Cortical neurophysiology of anticipatory anxiety: an investigation utilizing
      steady state probe topography (SSPT).
AB  - The precise role of the cortex in human anxiety is not well characterised.
      Previous imaging research among healthy controls has reported alterations in
      regional cerebral blood flow (rCBF) within the prefrontal and temporal cortices
      during periods of anxious anticipation; however, the temporal dynamics of this
      activity has yet to be examined in detail. The present study examined cortical
      Steady State Probe Topography (SSPT) changes associated with anticipatory anxiety
      (AA), allowing examination of the temporal continuity and the excitatory or
      inhibitory nature of AA activations. We recorded Steady State Visually Evoked
      Potentials (SSVEPs) at 64 scalp locations, skin conductance, and self reported
      anxiety among 26 right-handed males while relaxed and during the anticipation of
      an electric shock. Relative to the baseline condition, the AA condition was
      associated with significantly higher levels of self-reported anxiety and
      increased phasic skin conductance levels. Across the seven second imaging window,
      AA was associated with increased SSVEP latency within medial anterior frontal,
      left dorsolateral prefrontal and bilateral temporal regions. In contrast,
      increased SSVEP amplitude and decreased SSVEP latency were observed within
      occipital regions. The observed SSVEP latency increases within frontal and
      temporal cortical regions are suggestive of increased localised inhibitory
      processes within regions reciprocally connected to subcortical limbic structures.
      Occipital SSVEP latency decreases are suggestive of increased excitatory
      activity. SSVEP amplitude increases within occipital regions may be associated
      with an attentional shift from external to internal environment. The current
      findings provide further support for the involvement of frontal, anterior
      temporal, and occipital cortical regions during anticipatory anxiety, and suggest
      that both excitatory and inhibitory processes are associated with AA alterations.

PMID- 14568469
TI  - Determination of activation areas in the human auditory cortex by means of
      synthetic aperture magnetometry.
AB  - In this study we applied synthetic aperture magnetometry (SAM) to investigate
      active cortical areas associated with magnetically recorded transient and steady
      state auditory evoked responses. For transient evoked responses, SAM images
      reveal an activated volume of cortical tissue within the lateral aspect of the
      superior temporal plane. The volume of cortical activation for steady-state
      responses was located more medially than that for transient evoked responses.
      Additionally, SAM also reveals a small overlap of activated areas between
      transient and steady-state evoked responses, which has not be demonstrated when
      using equivalent current dipole (ECD) source modeling. Source waveforms from SAM
      and ECD analyses show comparable temporal information. Results from this study
      suggest that SAM is a useful technique for imaging cortical structures involved
      in processing perceptual information.

PMID- 14568468
TI  - Speech activation of language dominant hemisphere: a single-photon emission
      computed tomography study.
AB  - We tested the prediction that single photon emission computed tomography (SPECT)
      of the blood flow distribution in speech-activated brain identifies the language
      dominant hemisphere. We based the prediction on the hypothesis that language
      activation leads to focally increased regional cerebral blood flow (rCBF), which
      is reflected in the uptake of a flow tracer recorded by SPECT. We compared the
      results of speech activation to the results of functional transcranial Doppler
      (fTCD) monitoring in the same subjects. Preoperatively, 17 patients (10 women and
      7 men with a mean age of 36 +/- 15 years) with diagnoses of epilepsy (n = 14) or
      arteriovenous malformation (AVM) (n = 3) had two SPECT and two stereo-TCD
      monitoring studies in each case, one at rest, and one during 3 min of speech
      activation. Except for two left-handed patients with right-hemisphere dominance,
      the subjects had the highest changes of rCBF from baseline to activation in the
      left posterior inferior frontal cortex and in contralateral cerebellum. The
      results show that changes of the level of neuronal activity reflected by the
      measurement of rCBF variations might be detected by SPECT. Additionally, the
      evaluation of hemispheric language dominance based on SPECT showed a complete
      agreement with the evaluation based on fTCD results (yielding a kappa coefficient
      equal to 1), and therefore, speech-activation SPECT mapping might be helpful in
      the evaluation of hemispheric language dominance, especially when fMRI and PET
      are not available or they are contraindicated for some reason.

PMID- 14568470
TI  - fMRI BOLD response to increasing task difficulty during successful paired
      associates learning.
AB  - We used functional magnetic resonance imaging (fMRI) to assess cortical
      activations associated with increasing task difficulty (TD) in a visuospatial
      paired associates learning task. Encoding and retrieval were examined when 100%
      successful retrieval of three, four, or six object-location pairs had been
      attained (thus ensuring that performance was matched across subjects). As memory
      load increased, in general, the number of attempts taken to achieve 100%
      successful retrieval increased, while the number of trials correctly completed on
      the first attempt decreased. By modelling parametric variations in working memory
      load with BOLD signal changes we were able to identify brain regions displaying
      linear and nonlinear responses to increasing load. During encoding, load
      independent activations were found in occipitoparietal cortices (excluding the
      precuneus for which linear load dependency was demonstrated), anterior cingulate,
      and cerebellum, while linear load-dependent activations in these same regions
      were found during retrieval. Nonlinear load-dependent responses, as identified by
      categorical contrasts between levels of load, were found in the right DLPFC and
      left inferior frontal gyrus. The cortical response to increasing cognitive
      demands or TD appears to involve the same, rather than an additional, network of
      brain regions "working harder."

PMID- 14568471
TI  - Spatiotemporal dynamics of neural language processing: an MEG study using minimum
      norm current estimates.
AB  - The inferior frontal and superior temporal areas in the left hemisphere are well
      known to be crucial for language processing in most right-handed individuals.
      This has been established by classical neurological investigations and
      neuropsychological studies along with metabolic brain imaging have recently
      revealed converging evidence. Here, we use fast neurophysiological brain imaging,
      magnetoencephalography (MEG), and L1 Minimum-Norm Current Estimates to
      investigate the time course of cortical activation underlying the magnetic
      Mismatch Negativity elicited by a spoken word. Left superior-temporal areas
      became active 136 ms after the information in the acoustic input was sufficient
      for identifying the word, and activation of the left inferior-frontal cortex
      followed after an additional delay of 22 ms. By providing answers to the where-
      and when-questions of cortical activation, MEG recordings paired with current
      estimates of the underlying cortical sources may advance our understanding of the
      spatiotemporal dynamics of distributed neuronal networks involved in cognitive
      processing in the human brain.

PMID- 14568472
TI  - When the same response has different meanings: recoding the response meaning in
      the lateral prefrontal cortex.
AB  - The ability to adapt our behavioral repertoire to different situations and tasks
      is crucial for our behavioral control. Since the same motor behavior can have
      different meanings in different task situations, we often have to change the
      meaning of our responses when we get into a different task context. In a
      functional MRI experiment we manipulated this response recoding process. Subjects
      were required to execute two simple spatial tasks in a task switching paradigm.
      In one condition both tasks required the same set of responses, hence each
      response had two different meanings depending on the relevant task (bivalent
      condition). In the other condition subjects used a separate set of responses for
      each task (univalent condition). While subjects were required to recode the
      meaning when switching from one task to the next in the bivalent condition,
      response recoding was not required in the univalent condition. We demonstrate
      that the lateral prefrontal cortex is involved in recoding of response meaning.
      These results extend previous assumptions on the role of the prefrontal cortex in
      behavioral control.

PMID- 14568473
TI  - Verbal storage in a premotor-parietal network: evidence from fMRI-guided magnetic
      stimulation.
AB  - Phonological rehearsal helps to keep selected information consciously in mind for
      further processing. This part of short-term storage takes place during the delay
      period of verbal working memory tasks and involves a frontoparietal network as
      functional magnetic resonance imaging (fMRI) studies have shown. The involved
      cortical areas can be further investigated by interfering with the local
      information processing using transcranial magnetic stimulation (TMS). On a single
      subject level, we identified predominantly left-sided premotor, prefrontal, and
      parietal areas active during the delay period of a verbal working memory task
      using event-related fMRI. In a pilot approach, TMS was neuronavigated to the
      individually active areas by using a stereotaxic device. Then, TMS was applied
      during the delay period of similar tasks as in fMRI. Error rates increased
      significantly upon stimulating left premotor cortex, but not upon parietal or
      prefrontal stimulation. The contribution of the premotor cortex to storage and
      rehearsal is discussed as an active top-down storage process within the
      frontoparietal network.

PMID- 14568474
TI  - Word frequency and subsequent memory effects studied using event-related fMRI.
AB  - Event-related fMRI was used to evaluate the effect of printed word frequency on
      the subsequent recognition of words incidentally encoded while 16 healthy right
      handed volunteers performed living/nonliving judgments. Semantic judgment took
      longer for low-frequency words. These words were more accurately recognized than
      high-frequency words at later testing. Low-frequency words were also associated
      with relatively greater left prefrontal, left fusiform gyrus, and anterior
      cingulate activation. Words that were subsequently recognized were associated
      with greater activation in the left prefrontal region compared to those that were
      forgotten. These findings suggest the specific brain regions where less commonly
      encountered words are processed in a manner that facilitates their subsequent
      recognition.

PMID- 14568475
TI  - General multilevel linear modeling for group analysis in FMRI.
AB  - This article discusses general modeling of multisubject and/or multisession FMRI
      data. In particular, we show that a two-level mixed-effects model (where
      parameters of interest at the group level are estimated from parameter and
      variance estimates from the single-session level) can be made equivalent to a
      single complete mixed-effects model (where parameters of interest at the group
      level are estimated directly from all of the original single sessions' time
      series data) if the (co-)variance at the second level is set equal to the sum of
      the (co-)variances in the single-level form, using the BLUE with known
      covariances. This result has significant implications for group studies in FMRI,
      since it shows that the group analysis requires only values of the parameter
      estimates and their (co-)variance from the first level, generalizing the well
      established "summary statistics" approach in FMRI. The simple and generalized
      framework allows different prewhitening and different first-level regressors to
      be used for each subject. The framework incorporates multiple levels and cases
      such as repeated measures, paired or unpaired t tests and F tests at the group
      level; explicit examples of such models are given in the article. Using numerical
      simulations based on typical first-level covariance structures from real FMRI
      data we demonstrate that by taking into account lower-level covariances and
      heterogeneity a substantial increase in higher-level Z score is possible.

PMID- 14568476
TI  - Mapping of brain function after MPTP-induced neurotoxicity in a primate
      Parkinson's disease model.
AB  - Neurophysiological studies of the brain in normal and Parkinson's disease (PD)
      patients have indicated intricate connections for basal ganglia-induced control
      of signaling into the motor cortex. To investigate if similar mechanisms are
      controlling function in the primate brain (Macaca fascicularis) after MPTP
      induced neurotoxicity, we conducted PET studies of cerebral blood flow, oxygen
      and glucose metabolism, dopamine transporter, and D2 receptor function. Our
      observations after MPTP-induced dopamine terminal degeneration of the caudate and
      putamen revealed increased blood flow (15%) in the globus pallidus (GP), while
      blood flow was moderately decreased (15-25%) in the caudate, putamen, and
      thalamus and 40 % in the primary motor cortex (PMC). Oxygen extraction fraction
      was moderately increased (10-20%) in other brain areas but the thalamus, where no
      change was observable. Oxygen metabolism was increased in the GP and SMA
      (supplementary motor area including premotor cortex, Fig. 3) by a range of 20-40%
      and decreased in the putamen and caudate and in the PMC. Glucose metabolism was
      decreased in the caudate, putamen, thalamus, and PMC (range 35-50%) and enhanced
      in the GP by 15%. No change was observed in the SMA. In the parkinsonian primate,
      [(11)C]CFT (2beta-carbomethoxy-3beta-(4-fluorophenyltropane) dopamine transporter
      binding was significantly decreased in the putamen and caudate (range 60-65%).
      [(11)C]Raclopride binding of dopamine D(2) receptors did not show any significant
      changes. These experimental results obtained in primate studies of striato
      thalamo-cortico circuitry show a similar trend as hypothetized in Parkinson's
      disease-type degeneration.

PMID- 14568477
TI  - Self-responsibility and the self-serving bias: an fMRI investigation of causal
      attributions.
AB  - We use causal attributions to infer the most likely cause of events in the social
      world. Internal attributions imply self-responsibility for events. The self
      serving bias describes the tendency of normal subjects to attribute the causation
      of positive events internally ("I am responsible em leader ") and negative events
      externally ("Other people or situational factors are responsible em leader ").
      The self-serving bias has been assumed to serve a positive motivational function
      by enhancing self-esteem. Abnormalities of attributional style have been
      implicated in both depression and psychosis. We examined the neural basis of both
      self-responsibility and the self-serving bias using functional magnetic resonance
      imaging during the performance of attributional decision tasks. We found that the
      determination of self-responsibility recruits areas previously implicated in
      action simulation (bilateral premotor cortex and cerebellum), suggesting that
      such higher order social cognition is related to simpler internal models of goal
      directed action. The dorsal striatum, previously implicated in motivated
      behavior, mediates the self-serving bias.

PMID- 14568478
TI  - Anticipation of reward in a nonaversive differential conditioning paradigm and
      the brain reward system: an event-related fMRI study.
AB  - Findings from animal as well as human neuroimaging studies suggest that reward
      delivery is associated with the activation of subcortical limbic and prefrontal
      brain regions, including the thalamus, the striatum, the anterior cingulate and
      the prefrontal cortex. The aim of the present study was to explore if these
      reward-sensitive regions are also activated during the anticipation of
      reinforcers that vary with regard to their motivational value. A differential
      conditioning paradigm was performed, with the presentation of a rewarded reaction
      time task serving as the unconditioned stimulus (US). Depending on their reaction
      time, subjects were given (or not given) a monetary reward, or were presented
      with a verbal feedback consisting of being fast or slow. In a third control
      condition no task needed to be executed. Each of the three conditions was
      introduced by a different visual cue (CS). Brain activation of 27 subjects was
      recorded using event-related functional magnetic resonance imaging. The results
      showed significant activation of the substantia nigra, thalamic, striatal, and
      orbitofrontal brain regions as well as of the insula and the anterior cingulate
      during the presentation of a CS signalling a rewarded task. The anticipation of a
      monetary reward produced stronger activation in these regions than the
      anticipation of positive verbal feedback. The results are interpreted as
      reflecting the motivation-dependent reactivity of the brain reward system with
      highly motivating stimuli (monetary reward) leading to a stronger activation than
      those less motivating ones (verbal reward).

PMID- 14568479
TI  - Statistical properties of BOLD magnetic resonance activity in the human brain.
AB  - We investigated the random variability of BOLD (blood oxygen level dependent)
      activation during rest, or null-hypothesis, conditions in which the observers
      were neither receiving controlled sensory stimuli nor performing cognitive tasks.
      The data indicate that the distributions for the BOLD variation across space are
      skewed, with non-Gaussian tails, while the distributions for the temporal
      variation within individual voxels are predominantly Gaussian. The proportion of
      voxels that show non-Gaussian properties is highly correlated with the magnitude
      of head movement of the observers. In all observers, the white matter showed less
      variability than the gray matter. The distributions for the spatial and the
      temporal variations are robust across observers despite differences in the data
      acquisition methods (EPI vs. spiral) and magnetic field strength (1.5 vs. 3 T).
      In most cases, the non-Gaussian tails of the spatial distribution can be
      eliminated by normalizing the amplitude in each voxel to its standard deviation
      before cumulating across voxels. We therefore recommend such a normalization
      procedure before any data manipulations are performed on fMRI data.

PMID- 14568480
TI  - Modulation of brain magnetic activity by different verbal learning strategies.
AB  - In this study we examined spatiotemporal profiles of brain activity in the
      context of tasks designed to engage different verbal learning strategies (serial
      order, phonological, and semantic). The profile of activation associated with the
      serial-order strategy, which resulted in poor recall performance, featured early
      activation of the inferior frontal, sensorimotor, and insular region in the left
      hemisphere, between 200 and 400 ms after stimulus onset. Subsequently, activation
      was more prominent in dorsolateral prefrontal cortices bilaterally. In contrast,
      activation profiles associated with the phonological strategy featured
      predominantly activation of the superior temporal gyrus in the left hemisphere
      between 500 and 600 ms. Predominant activation of the left middle temporal gyrus,
      between 500 and 700 ms, was the key feature of the activation profile observed
      when the semantic elaboration strategy was utilized. These results suggest that
      different brain circuits are engaged to support learning of new verbal
      information as a function of the level and type of initial processing applied to
      the stimuli.

PMID- 14568481
TI  - The shape of the fMRI BOLD response in children and adults changes systematically
      with age.
AB  - We measured the shape of the BOLD response to visual stimulation in subjects
      between 7 and 61 years of age. We performed two experiments. In the first
      experiment, at low temporal resolution (TR = 1 s) and with long stimulus periods,
      we determined activated voxels in each subject. In the second experiment, at high
      temporal resolution (TR = 294 ms), we measured the response to an impulse
      stimulus in these voxels. We found that the shape of the time course changes
      systematically with age. Among the parameters whose age dependence we determined
      quantitatively, we found the smallest effect for the latency of the leading edge.
      Therefore, in order to avoid the potential confounds resulting from this effect,
      it may be appropriate to use the latency of the leading edge or the peak
      intensity of the BOLD signal, rather than its trailing edge or the area under the
      signal, as the salient variable in event-related studies that compare groups of
      different age.

PMID- 14568482
TI  - A midline dissociation between error-processing and response-conflict monitoring.
AB  - Midline brain activation subsequent to errors has been proposed to reflect error
      detection and, alternatively, conflict-monitoring processes. Adjudicating between
      these alternatives is challenging as both predict high activation on error
      trials. In an effort to resolve these interpretations, subjects completed a
      GO/NOGO task in which errors of commission were frequent and response conflict
      was independently varied by manipulating response speeds. A mixed-block and event
      related fMRI design identified task-related, tonic activation and event-related
      activations for correct and incorrect trials. The anterior cingulate was the only
      area with error-related activation that was not modulated by the conflict
      manipulation and hence is implicated in specific error-related processes.
      Conversely, activation in the pre-SMA was not specific to errors but was
      sensitive to the conflict manipulation. A significant region by conflict
      interaction for tonic activation supported a functional dissociation between
      these two midline areas. Finally, an intermediate, caudal cingulate area was
      implicated in both error processing and conflict monitoring. The results suggest
      that these two action-monitoring processes are distinct and dissociable and are
      localised along the midline.

PMID- 14568483
TI  - An error analysis of white matter tractography methods: synthetic diffusion
      tensor field simulations.
AB  - White matter tractography using diffusion tensor MR images is a promising method
      for estimating the pathways of white matter tracts in the human brain. The
      success of this method ultimately depends upon the accuracy of the white matter
      tractography algorithms. In this study, a Monte Carlo simulation was used to
      investigate the impact of SNR, tensor anisotropy, and diffusion tensor encoding
      directions on the accuracy of six tractography algorithms. The accuracy was
      assessed in straight and curved tracts and tract geometries with divergence
      properties. In general, the tract dispersion increased with distance and
      decreased with SNR and anisotropy. The tract orientation with respect to the
      encoding scheme also influenced tract dispersion. Divergent tract geometries
      increased tract dispersion, whereas convergent tract geometries reduced
      dispersion. Analytic models of tract dispersion were constructed as a function of
      the tract distance, SNR, eigenvalues of the tracts, voxel size, and the
      relationship between the tract direction and the diffusion tensor encoding
      directions. In certain cases, the mean tract trajectory was found to deviate from
      the ideal pathway for curved trajectories. Analytical models of mean displacement
      were constructed as a function of the curvature, tract distance, step size, and
      tensor eigenvalues. These models may be used in future studies to assess the
      level of confidence associated with a tractography result.

PMID- 14568484
TI  - Functional brain maps of Tower of London performance: a positron emission
      tomography and functional magnetic resonance imaging study.
AB  - Regional cerebral blood flow (rCBF) and blood oxygenation level-dependent (BOLD)
      contrasts represent different physiological measures of brain activation. The
      present study aimed to compare two functional brain imaging techniques
      (functional magnetic resonance imaging versus [(15)O] positron emission
      tomography) when using Tower of London (TOL) problems as the activation task. A
      categorical analysis (task versus baseline) revealed a significant BOLD increase
      bilaterally for the dorsolateral prefrontal and inferior parietal cortex and for
      the cerebellum. A parametric haemodynamic response model (or regression analysis)
      confirmed a task-difficulty-dependent increase of BOLD and rCBF for the
      cerebellum and the left dorsolateral prefrontal cortex. In line with previous
      studies, a task-difficulty-dependent increase of left-hemispheric rCBF was also
      detected for the premotor cortex, cingulate, precuneus, and globus pallidus.
      These results imply consistency across the two neuroimaging modalities,
      particularly for the assessment of prefrontal brain function when using a
      parametric TOL adaptation.

PMID- 14568485
TI  - Using patient-specific hemodynamic response functions in combined EEG-fMRI
      studies in epilepsy.
AB  - Combining electroencephalogram (EEG) and functional MRI (fMRI) allows
      localization of brain regions activated as a result of epileptic spikes. The
      statistical analysis of fMRI data usually includes a standard model of the
      hemodynamic response function (HRF) but it is not known how well this fits the
      actual HRF of epileptic spikes. The objective of this exploratory study was to
      compare the activated areas and t-statistical scores obtained with a standard HRF
      to those obtained with a patient-specific HRF. Eight patients with focal epilepsy
      were studied. We obtained an estimate of the patient-specific HRFs for each
      patient at the local maximum of activation in the standard HRF analysis. The
      activated areas obtained with the patient-specific HRFs were larger or similar to
      the originally activated areas. Additional activated areas were seen in five
      patients, and most were compatible with the EEG and anatomical MRI localization
      of epileptogenic and lesional regions. Using patient-specific HRFs brings
      increased sensitivity to the analysis of epileptic spikes by EEG-fMRI.

PMID- 14568486
TI  - Functional cerebral reorganization following motor sequence learning through
      mental practice with motor imagery.
AB  - The goal of the present study was to examine, via positron emission tomography,
      the functional changes associated with the learning of a sequence of foot
      movements through mental practice with motor imagery (MI). Following intensive MI
      training over several days, which led to a modest but significant improvement in
      performance, healthy subjects showed an increase in activity restricted to the
      medial aspect of the orbitofrontal cortex (OFC), and a decrease in the
      cerebellum. These main results are largely consistent with those found in a
      previous study of sequence learning performed in our laboratory after physical
      practice of the same task [NeuroImage 16 (2002) 142]. Further analyses showed a
      positive correlation between the blood flow increase in the OFC and the
      percentage of improvement on the foot sequence task. Moreover, the increased
      involvement of the medial OFC revealed a modality specific anatomo-functional
      organization, as imagination of the sequential task after MI practice activated a
      more posterior region than its execution. These results demonstrate that learning
      a sequential motor task through motor imagery practice produces cerebral
      functional changes similar to those observed after physical practice of the same
      task. Moreover, the findings are in accord with the hypothesis that mental
      practice with MI, at least initially, improves performance by acting on the
      preparation and anticipation of movements rather than on execution per se.

PMID- 14568487
TI  - Differences between auditory evoked responses recorded during spatial and
      nonspatial working memory tasks.
AB  - Results from several recent studies suggest that neuronal processing of sound
      content and its spatial location may be dissociated. The use of modern
      neuroimaging techniques has allowed for the determination that different brain
      structures may be specifically activated during working memory processing of
      pitch and location of sound. The time course of these task-related differences,
      however, remains uncertain. In the present study, we performed simultaneous whole
      head electroencephalogram and magnetoencephalogram recordings, using a new
      behavioral paradigm, to investigate the dynamics of differences between "what"
      and "where" evoked responses in the auditory system as a function of memory load.
      In the location task the latency of the N1m was shorter and its generator was
      situated more inferiorly than in the pitch task. Working memory processing of the
      tonal frequency enhanced the amplitude of the N2 component, as well as the
      negative-going deflection at a latency around 400 ms. A memory-load-dependent
      task-related difference was found in the positive slow wave which was higher
      during the location than pitch task at the low load. Late slow waves were
      affected by memory load but not type of task. These results suggest that separate
      neuronal networks are involved in the attribute-specific analysis of auditory
      stimuli and their encoding into working memory, whereas the maintenance of
      auditory information is accomplished by a common, nonspecific neuronal network.

PMID- 14568488
TI  - Time-series analysis of MRI intensity patterns in multiple sclerosis.
AB  - In progressive neurological disorders, such as multiple sclerosis (MS), magnetic
      resonance imaging (MRI) follow-up is used to monitor disease activity and
      progression and to understand the underlying pathogenic mechanisms. This article
      presents image postprocessing methods and validation for integrating multiple
      serial MRI scans into a spatiotemporal volume for direct quantitative evaluation
      of the temporal intensity profiles. This temporal intensity signal and its
      dynamics have thus far not been exploited in the study of MS pathogenesis and the
      search for MRI surrogates of disease activity and progression. The integration
      into a four-dimensional data set comprises stages of tissue classification,
      followed by spatial and intensity normalization and partial volume filtering.
      Spatial normalization corrects for variations in head positioning and distortion
      artifacts via fully automated intensity-based registration algorithms, both rigid
      and nonrigid. Intensity normalization includes separate stages of correcting
      intra- and interscan variations based on the prior tissue class segmentation.
      Different approaches to image registration, partial volume correction, and
      intensity normalization were validated and compared. Validation included a scan
      rescan experiment as well as a natural-history study on MS patients, imaged in
      weekly to monthly intervals over a 1-year follow-up. Significant error reduction
      was observed by applying tissue-specific intensity normalization and partial
      volume filtering. Example temporal profiles within evolving multiple sclerosis
      lesions are presented. An overall residual signal variance of 1.4% +/- 0.5% was
      observed across multiple subjects and time points, indicating an overall
      sensitivity of 3% (for axial dual echo images with 3-mm slice thickness) for
      longitudinal study of signal dynamics from serial brain MRI.

PMID- 14568489
TI  - Functional magnetic resonance imaging at 0.2 Tesla.
AB  - Functional magnetic resonance imaging of healthy human volunteers was carried out
      at 0.2 T, using proton-density weighted (TE = 24 ms) spin-echo imaging, in order
      to eliminate any contribution from the blood oxygenation-level dependent (BOLD)
      effect. The purpose of the study was to verify the existence of a proton-density
      change contribution to spin-echo functional magnetic resonance imaging (fMRI)
      data. Results demonstrated signal intensity changes in motor and sensory areas of
      the brain during performance of a motor task and cold sensory stimulation of the
      hand, with signal changes ranging from 1.7 to 2.3%. These values are consistent
      with 1.9% signal changes observed previously under similar conditions at 3 T.
      These findings confirm the proton-density change contribution to spin-echo fMRI
      data and support the theory of signal enhancement by extravascular water protons
      (SEEP) as a non-BOLD fMRI contrast mechanism. This study also demonstrates that
      fMRI based on the SEEP contrast mechanism can be carried out at low fields where
      the BOLD effect is expected to be negligible.

PMID- 14568490
TI  - The morphometry of auditory cortex in the congenitally deaf measured using MRI.
AB  - The study of congenitally deaf individuals provides a unique opportunity to
      understand the organization and potential for reorganization of human auditory
      cortex. We used magnetic resonance imaging (MRI) to examine the structural
      organization of two auditory cortical regions, Heschl's gyrus (HG) and the planum
      temporale (PT), in deaf and hearing subjects. The results show preservation of
      cortical volume in HG and PT of deaf subjects deprived of auditory input since
      birth. Measurements of grey and white matter, as well as the location and extent
      of these regions in the deaf showed complete overlap both with matched controls
      and with previous samples of hearing subjects. The results of the manual volume
      measures were supported by findings from voxel-based morphometry analyses that
      showed increased grey-matter density in the left motor hand area of the deaf, but
      no differences between the groups in any auditory cortical region. This increased
      cortical density in motor cortex may be related to more active use of the
      dominant hand in signed languages. Most importantly, expected interhemispheric
      asymmetries in HG and PT thought to be related to auditory language processing
      were preserved in these deaf subjects. These findings suggest a strong genetic
      component in the development and maintenance of auditory cortical asymmetries
      that does not depend on auditory language experience. Preservation of cortical
      volume in the deaf suggests plasticity in the input and output of auditory cortex
      that could include language-specific or more general-purpose information from
      other sensory modalities.

PMID- 14568491
TI  - Increased bilateral occipitoparietal activity during retention of binary versus
      unary indexed lists in pair recognition.
AB  - Cognitive complexity has been characterized by relations processed, rather than
      items stored. Separating these factors is difficult, because processing more
      complex relations often involves holding more items in memory. Previous research,
      NeuroImage, 17, 1031-1055) identified parietal lobes with more item
      relationships, but not more items by varying index length-fewest number of
      positions having a unique combination of items. For example, AB CD EF is a unary
      (length one) indexed list of three pairs, because all items are unique at the
      first (or second) position; AB AD CB is a binary indexed list, because only pairs
      of items are unique. But, these lists also differ in number of associates. In
      this experiment, index length was varied independently of the numbers of items
      and associates. Subjects were asked to make a recognition judgment for each three
      pair list: Was the test pair in the previous list? Random effects analysis
      contrasting two binary indexed lists (AB AC CB and AB AD CB) minus two unary
      indexed lists (AB BC CA and AB BC CD) revealed increased occipital and parietal
      activity (bilaterally) during the retention period for both binary indexed list
      types. This result is explained by index length, but not by item load or item
      fan, because the numbers of items and item associates were the same for the
      corresponding unary and binary list types. For peak voxels in left and right
      precuneus, activity during retention for both binary list types was also greater
      than for a third unary indexed list (AB CD EF). Because binary indexes require
      more positions (roles) to individuate pairs, we suggest that the increased
      activity in precuneus relates to spatial rehearsal in that more attention is
      directed to both positions to maintain the integrity of the memory trace.

PMID- 14568493
TI  - Transient hemodynamics during a breath hold challenge in a two part functional
      imaging study with simultaneous near-infrared spectroscopy in adult humans.
AB  - During a breath hold (BH) challenge, functional MR imaging using flow-sensitive
      alternating inversion recovery (FAIR) and blood oxygenation level dependent
      (BOLD) contrast was performed with simultaneous near-infrared spectroscopy
      (NIRS). Time courses for the BOLD signal, cerebral blood flow (CBF), absolute
      deoxyhemoglobin (Hb) concentration, and relative concentration changes for total
      hemoglobin (HbT) were generated to (1) characterize the relationship between
      transient BOLD responses and the transient hemodynamic response, and (2) compare
      results from previous empirical animal experiments. During this mild hypercapnia
      task, the increase in the BOLD signal during the task indicated that an increase
      in CBF outweighed the competing effect of a volume-induced increase in Hb. After
      the task, the increase in the concentration of Hb mirrored the posttask
      undershoot in the BOLD and CBF data. Finally, we found a strong linear
      relationship between R(2)(*) and absolute Hb, except for outlier points in the Hb
      time series corresponding to the task cessation, which suggests there are
      differences in measurement sensitivity between BOLD and NIRS.

PMID- 14568492
TI  - Identifying confounds to increase specificity during a "no task condition".
      Evidence for hippocampal connectivity using fMRI.
AB  - Functional MRI can be applied to study connectivity in the brain during a "no
      task condition." This study focuses on applying a multiple linear regression
      analysis to identify spurious connectivity caused by confounding factors such as
      physiologic noise and to separate these from hippocampal connectivity caused by
      the blood oxygen level dependent (BOLD) signal during a no-task condition.
      Regressors of interest (hippocampal time courses) as well as regressors of no
      interest (respiratory signal and cerebrospinal fluid), were included in the
      analysis, and each yielded a connectivity map. This method was applied at high
      sampling rate (limited volume, proper physiologic noise sampling), low sampling
      rate (whole brain scans possible), and at high and low spatial resolution in five
      healthy control subjects. Regressors of no interest showed specific connectivity
      patterns, different from hippocampal regressors. The latter showed connectivity
      between left and right hippocampus. The current study shows successful
      application of a multiple regression analysis to study connectivity between left
      and right hippocampus. Both maps of hippocampal connectivity caused by BOLD
      signal and connectivity caused by spurious signals could be identified.

PMID- 14568494
TI  - Serial contrast-enhanced magnetic resonance imaging and spectroscopic imaging of
      acute multiple sclerosis lesions under high-dose methylprednisolone therapy.
AB  - To evaluate biochemical changes in contrast-enhancing multiple sclerosis (MS)
      lesions, we examined 14 patients with relapsing-remitting MS at acute clinical
      exacerbation with the help of contrast-enhanced magnetic resonance imaging (MRI)
      and 1H magnetic resonance spectroscopic imaging (1H MRSI). Using a 1.5-tesla MR
      system (Magnetom Vision, Siemens, Germany), we followed 29 contrast-enhancing and
      24 nonenhancing MS lesions as well as normal-appearing white matter (NAWM) before
      and during high-dose methylprednisolone (HDMP) therapy. Metabolite ratios of N
      acetylaspartate (NAA), choline (Cho), creatine (Cr), and lactate (Lac) were
      calculated. A transient decrease in contrast enhancement under HDMP therapy was
      observed. Both groups of MS lesions showed significantly decreased NAA to Cr
      ratios compared to NAWM with no changes in time. Baseline 1H MRSI revealed
      significantly increased Cho to Cr ratios in the contrast-enhancing MS lesions
      (1.13 +/- 0.25) compared to the nonenhancing MS lesions (0.85 +/- 0.26, P <
      0.001) and NAWM (0.97 +/- 0.22, P = 0.015). Both the contrast-enhancing and the
      nonenhancing MS lesions exhibited a significant increase in Cho to Cr ratios from
      the second to the third 1H MRSI. We identified resonances of lactate in both
      groups of MS lesions and NAWM without any significant group differences or
      changes over time. 1H MRSI provides additional information that help to estimate
      macrophages' activity, cell membrane activation, and neuronal impairment within
      MS lesions. We believe that combined contrast-enhanced MRI and 1H MRSI may help
      to further investigate inflammatory processes within active MS lesions and should
      be employed more frequently to the research on therapy effects in MS.

PMID- 14568495
TI  - Approaching an ecologically valid functional anatomy of spontaneous "willed"
      action.
AB  - We used functional magnetic resonance imaging of healthy subjects to investigate
      the neural basis for spontaneous "willed" action. We hypothesised that such
      action involves prefrontal cortex (PFC) and supplementary motor area (SMA), in
      addition to primary motor cortex. Furthermore, we predicted that PFC and SMA
      would demonstrate similar temporal response dynamics, distinct from primary motor
      cortex. Specifically, we predicted earlier activation in PFC and SMA, manifest as
      shorter response latencies compared with primary motor cortex. Six right-handed
      males participated in an event-related design and were required to generate
      spontaneous motor acts inside the scanner. By deciding "which" of two buttons to
      press, and "when" to press them, subjects generated sequences of action that were
      of high information content ("novelty" or "randomness"). Utilising a short
      repetition time (1 s), we acquired functional images that covered most of the
      frontal and parietal cortices. The onset of action was associated with
      significant activation in bilateral PFC, left primary motor cortex, and, close to
      the midline, SMA. Following action, mean time to half-maximum blood oxygenation
      level-dependent response was significantly earlier in left PFC and SMA than
      primary motor cortex. Our findings suggest that neural correlates of spontaneous
      willed action are distributed in executive and motor centres, and that temporal
      response dynamics differentiate "higher" regions from subordinate motor areas.

PMID- 14568496
TI  - Prefrontal cortex involvement in preattentive auditory deviance detection:
      neuroimaging and electrophysiological evidence.
AB  - Previous electrophysiological and neuroimaging studies suggest that the mismatch
      negativity (MMN) is generated by a temporofrontal network subserving preattentive
      auditory change detection. In two experiments we employed event-related brain
      potentials (ERP) and event-related functional magnetic resonance imaging (fMRI)
      to examine neural and hemodynamic activity related to deviance processing, using
      three types of deviant tones (small, medium, and large) in both a pitch and a
      space condition. In the pitch condition, hemodynamic activity in the right
      superior temporal gyrus (STG) increased as a function of deviance. Comparisons
      between small and medium and between small and large deviants revealed right
      prefrontal activation in the inferior frontal gyrus (IFG; BA 44/45) and middle
      frontal gyrus (MFG; BA 46), whereas large relative to medium deviants led to left
      and right IFG (BA 44/45) activation. In the ERP experiment the amplitude of the
      early MMN (90-120 ms) increased as a function of deviance, by this paralleling
      the right STG activation in the fMRI experiment. A U-shaped relationship between
      MMN amplitude and the degree of deviance was observed in a late time window (140
      170 ms) resembling the right IFG activation pattern. In a subsequent source
      analysis constrained by fMRI activation foci, early and late MMN activity could
      be modeled by dipoles placed in the STG and IFG, respectively. In the spatial
      condition no reliable hemodynamic activation could be observed. The MMN amplitude
      was substantially smaller than in the pitch condition for all three spatial
      deviants in the ERP experiment. In contrast to the pitch condition it increased
      as a function of deviance in the early and in the late time window. We argue that
      the right IFG mediates auditory deviance detection in case of low
      discriminability between a sensory memory trace and auditory input. This
      prefrontal mechanism might be part of top-down modulation of the deviance
      detection system in the STG.

PMID- 14568497
TI  - Neurophysiological correlates of error correction in sensorimotor
      synchronization.
AB  - In a sensorimotor synchronization task requiring subjects to tap in synchrony
      with an auditory stimulus, occasional perturbations (i.e., interval changes) in
      an otherwise isochronous sequence of auditory metronome stimuli are known to be
      compensated remarkably swift and with surprising precision, even when they are
      too small to be consciously perceived. To investigate the neural substrate and
      the informational basis of error correction in sensorimotor synchronization, we
      recorded movement-related, auditory-evoked, and error-related EEG potentials.
      Experiment 1 confirmed rapid adjustment to stimulus phase shifts, with faster
      correction of large (50 ms) compared to small (15 ms) shifts. In addition to
      being corrected faster, there was overcorrection of the 50 ms shifts, attributed
      to engagement of period correction mechanisms. For +50 ms shifts, a neural
      correlate of period correction was identified in the form of medial frontal
      cortex activation, preceded by an error-related brain potential (ERN). Auditory
      evoked potential (AEP) amplitudes were sensitive to stimulus phase shifts of both
      large and small magnitude. Further experiments with a smaller magnitude 10 ms
      phase shift (Experiment 2) and passive auditory stimulation (Experiment 3)
      provided evidence that the modulation of AEP amplitudes is not due to metronome
      interval changes, but may represent auditory-somatosensory activation. Together,
      behavioral and neurophysiological data support the hypothesis that phase
      correction is a largely automatic process, not dependent on conscious perception
      of changes in timing. By contrast, perceivable phase shifts may invoke timekeeper
      adjustments accompanied by medial frontal cortex activity.

PMID- 14568498
TI  - Co-ordination within and between verbal and visuospatial working memory: network
      modulation and anterior frontal recruitment.
AB  - Attention switching between items being stored and manipulated in working memory
      (WM) is proposed to be an elementary executive function. Experiment 1 reveals a
      similar attentional limitation within and between verbal and visuospatial WM and
      identifies a supramodal switching process required for switching between WM
      items. By using functional magnetic resonance imaging, Experiment 2 investigated
      brain activation correlates of parametrically varied attention switching within
      and between these two WM modalities. Attention switching activation was broadly
      distributed, was quite similar across the three conditions, and, in almost all
      areas, increased with increasing switching demand, indicating that attention
      switching recruits and modulates the entire WM network. Dorsolateral prefrontal
      cortex was implicated in both within- and between-modality attention switching,
      but no significant activation was found in ventrolateral areas, supporting dorsal
      ventral process models of prefrontal organization. A functional dissociation
      between anterior frontal and dorsolateral prefrontal cortex was found with the
      former being more activated when switching attention between modalities was
      required. The data challenge the notion of an anatomically separate attention
      switching executive function, but suggest that anterior frontal areas are
      recruited for the additional demand of coordinating the verbal and visuospatial
      WM slave systems.

PMID- 14568499
TI  - Regional cerebral blood flow in Parkinson's disease with and without dementia.
AB  - Tc99 HMPAO SPECT and T1 weighted 3D MRI scans were acquired in cognitively intact
      subjects with Parkinson's disease (PD) (n = 31), and in PD subjects with dementia
      (PDD) (n = 34), healthy controls (n = 37), those with Alzheimer's disease (AD) (n
      = 32), and those with dementia with Lewy bodies (DLB) (n = 15). We used SPM99 to
      look for regions which showed a reduction in perfusion on SPECT not related to
      associated structural brain changes assessed by a MRI scan. The precuneus and
      inferior lateral parietal regions showed a perfusion deficit in Parkinson's
      disease with dementia, similar to the pattern observed in DLB. In comparison, AD
      showed a perfusion deficit in the midline parietal region, in a more anterior and
      inferior location than in PDD, involving the posterior cingulate as well as the
      precuneus. The perfusion deficits in PDD are similar those in DLB, and in a
      location associated with visual processing, and may be associated with the
      visuospatial perception deficits which are present in persons with DLB and PDD.

PMID- 14568500
TI  - Effects of noise from functional magnetic resonance imaging on auditory event
      related potentials in working memory task.
AB  - The effects of functional magnetic resonance imaging (fMRI) acoustic noise were
      investigated on the parameters of event-related responses (ERPs) elicited during
      auditory matching-to-sample location and pitch working memory tasks. Stimuli were
      tones with varying location (left or right) and frequency (high or low). Subjects
      were instructed to memorize and compare either the locations or frequencies of
      the stimuli with each other. Tape-recorded fMRI acoustic noise was presented in
      half of the experimental blocks. The fMRI noise considerably enhanced the P1
      component, reduced the amplitude and increased the latency of the N1, shortened
      the latency of the N2, and enhanced the amplitude of the P3 in both tasks. The N1
      amplitude was higher in the location than pitch task in both noise and no-noise
      blocks, whereas the task-related N1 latency difference was present in the no
      noise blocks only. Although the task-related differences between spatial and
      nonspatial auditory responses were partially preserved in noise, the finding that
      the acoustic gradient noise accompanying functional MR imaging modulated the
      auditory ERPs implies that the noise may confound the results of auditory fMRI
      experiments especially when studying higher cognitive processing.

PMID- 14568501
TI  - Task-specific plasticity of somatosensory cortex in patients with writer's cramp.
AB  - Focal dystonias such as writer's cramp are characterized by muscular cramps that
      accompany the execution of specific motor tasks. Until now, the pathophysiology
      of focal dystonia remains incompletely understood. Recent studies suggest that
      the development of writer's cramp is related to abnormal organization of primary
      somatosensory cortex (SI), which in turn leads to impaired motor function. To
      explore contributions of SI on mechanisms of task specificity in focal dystonia,
      we investigated dynamic alterations in the functional organization of SI as well
      as sensory-motor gating for rest, left- and right-handed writing and brushing in
      writer's cramp patients and healthy controls. The functional organization of
      somatosensory cortex was assessed by neuromagnetic source imaging (151 channel
      whole-head MEG). In accordance with previous reports, distances between cortical
      representations of thumb and little finger of the affected hand were smaller in
      patients compared to healthy subjects. However, similar to healthy controls,
      patients showed normal modulation of the functional organization of SI as induced
      by the execution of different motor tasks. Both in the control subjects and
      patients, cortical distances between representations of thumb and little finger
      increased when writing and brushing compared to the resting condition. Although,
      cramps only occured during writing, no differences in the organization of SI were
      seen among motor tasks. Our data suggest that despite alterations in the
      organization of primary somatosensory cortex in writer's cramp, the capability of
      SI to adapt dynamically to different tasks is not impaired.

PMID- 14568502
TI  - Evidence of enhancement of spatial attention during inhibition of a visuo-motor
      response.
AB  - A visuo-motor task was used as the setting for a study into inhibition in six
      healthy volunteers using fMRI. The task involved responding to colored stimuli,
      which appeared at random positions in the left and right visual field, with the
      corresponding hand. The volunteers were asked to respond to green colored stimuli
      ("go" response) and to inhibit responses to red stimuli ("no-go" response). The
      task was presented in a block design with blocks of three types; only "go"
      trials, a pseudo-random mixture of "go" and "no-go" tasks ("go/no-go" block), and
      "visual control." ANCOVA analysis of the fMRI data was performed within the
      framework of SPM99. Increased activation in the go vs visual control comparison
      was found in the bilateral motor and medial premotor cortices associated with the
      action of the button press response, as well as parietal regions attending to the
      task of identifying the visual field. The go/no-go vs visual control comparison
      showed a similar pattern, plus additional prefrontal areas that have previously
      been shown to be associated with inhibition. The direct comparison of the go and
      go/no-go blocks highlighted large differences not only in the prefrontal
      cortices, associated with inhibition, but also particularly in the right parietal
      cortex. We interpret the increased parietal activation, during inhibition, as
      representing a heightened spatial attention required for the correct execution of
      the inhibition task.

PMID- 14568503
TI  - Bayesian second-level analysis of functional magnetic resonance images.
AB  - We propose a new method for the second-level analysis of functional MRI data
      based on Bayesian statistics. Our method does not require a computationally
      costly Bayesian model on the first level of analysis. Rather, modeling for single
      subjects is realized by means of the commonly applied General Linear Model. On
      the basis of the resulting parameter estimates for single subjects we calculate
      posterior probability maps and maps of the effect size for effects of interest in
      groups of subjects. A comparison of this method with the conventional analysis
      based on t statistics shows that the new approach is more robust against
      outliers. Moreover, our method overcomes some of the severe problems of null
      hypothesis significance tests such as the need to correct for multiple
      comparisons and facilitates inferences which are hard to formulate in terms of
      classical inferences.

PMID- 14568504
TI  - Evidence for compensation for stuttering by the right frontal operculum.
AB  - There is recent evidence of focal alteration in fibre tracts underlying the left
      sensorimotor cortex in persistent developmental stuttering (PDS) [Lancet 360
      (2002) 380]. If, as proposed, this anatomical abnormality is the cause of PDS,
      then overactivation in the right hemisphere seen with functional neuroimaging in
      stutterers may reflect a compensatory mechanism. To investigate this hypothesis,
      we performed two functional magnetic resonance imaging (fMRI) experiments. The
      first showed systematic activation of a single focus in the right frontal
      operculum (RFO) in PDS subjects during reading, which was not observed in
      controls. Responses in this region were negatively correlated with the severity
      of stuttering, suggesting compensation rather than primary dysfunction. Negative
      correlation was also observed during the baseline task that consisted in passive
      viewing of meaningless signs, indicating that RFO compensation acts independently
      of specific demands on motor speech output. The second experiment, that involved
      a covert semantic decision task, confirmed that RFO activation does not require
      overt utterances or motor output. In combination these findings suggest that the
      RFO serves a nonspecific compensatory role rather than one restricted to the
      final stages of speech production.

PMID- 14568505
TI  - Sustained blood oxygenation and volume response to repetition rate-modulated
      sound in human auditory cortex.
AB  - The blood oxygen level-dependent (BOLD) signal time course in the auditory cortex
      is characterized by two components, an initial transient peak and a subsequent
      sustained plateau with smaller amplitude. Because the T(2)(*) signal detected by
      functional magnetic resonance imaging (fMRI) depends on at least two
      counteracting factors, blood oxygenation and volume, we examined whether the
      reduction in the sustained BOLD signal results from decreased levels of
      oxygenation or from increased levels of blood volume. We used conventional fMRI
      to quantify the BOLD signal and fMRI in combination with superparamagnetic
      contrast agent to quantify blood volume and employed repetition rate-modulated
      sounds in a silent background to manipulate the response amplitude in the
      auditory cortex. In the BOLD signal, the initial peak reached 3.3% with pulsed
      sound and 1.9% with continuous sound, whereas the sustained BOLD signal fell to
      2.2% with pulsed sound and to 0.5% with continuous sound, respectively. The
      repetition rate-dependent reduction in the sustained BOLD amplitude was
      accompanied by concordant changes in sustained blood volume levels, which,
      compared to silence, increased by approximately 30% with pulsed and by
      approximately 10% with continuous sound. Thus, our data suggest that the reduced
      amplitude of the sustained BOLD signal reflects stimulus-dependent modulation of
      blood oxygenation rather than blood volume-related effects.

PMID- 14568506
TI  - Neural correlates of rapid reversal learning in a simple model of human social
      interaction.
AB  - Humans and other primates spend much of their time engaged in social interactions
      where a crucial ability is to decode face expressions and act accordingly. This
      rapid reversal learning has been proposed to be important in the relative
      evolutionary success of primates. Here we provide the first neuroimaging evidence
      that the ability to change behaviour based on face expression in a model of
      social interactions is not reflected in the activity in the fusiform face area,
      but is specifically correlated with activity in the orbitofrontal and anterior
      cingulate/paracingulate cortices. These brain regions are particularly involved
      in reversal learning, such that the activations described occurred specifically
      at the time of reversal, and were also found when different face expressions
      other than angry were used to cue reversal. The evidence that the orbitofrontal
      and anterior cingulate/paracingulate cortices are specifically activated at the
      time of reversal is important for understanding changes in affect and emotional
      processing in patients with lesions to these brain regions.

PMID- 14568507
TI  - Frontal recruitment during response inhibition in older adults replicated with
      fMRI.
AB  - Recent research has explored age-related differences in multiple areas of
      cognitive functioning using fMRI, PET, and SPECT. However, because these studies
      used different tasks, subjects, and methods, little is known about whether the
      results of these studies are generalizable or repeatable. The present study
      replicated a previous study [Psychol. Aging 17 (2002) 56] using the same Go/No-go
      task with a subset of 11 of the original older adult subjects, and using the same
      fMRI scanner and imaging methods. A direct comparison was made between these
      participants at Time 1 and Time 2 for both behavioral and functional data. These
      participants were also compared to a new young adult group of 11 participants.
      Although the current young adult group did not perform as well as the original
      young adult group, the original finding of enhanced left prefrontal activation in
      older adults relative to younger adults was replicated. Furthermore, when
      comparing Time 1 to Time 2, older adults exhibited comparable areas of
      activation, but significantly greater magnitude of activation at Time 1 in a few
      clusters. The findings indicate that older adults exhibit more bilateral brain
      activity during this task than young adults, which appears compensatory and is
      repeatable over time. The magnitude of regional activation, however, may vary
      with extraneuronal factors such as signal-to-noise ratio or task experience. This
      study adds to existing research suggesting that bilateral frontal activation is a
      predominant finding in the aging literature, and not specific to certain tasks in
      age group comparisons.

PMID- 14568508
TI  - The influence of extra- and intracranial artery disease on the BOLD signal in
      FMRI.
AB  - Functional MRI is based on the vascular response due to neuronal activation. The
      underlying mechanism of fMRI is the blood oxygenation level-dependent (BOLD)
      effect-a complex interplay between changes in the cerebral metabolisation rate of
      oxygen (CMRO2), neurovascular coupling, and the resulting hemodynamic response.
      An intact neurovascular coupling is essential for the detection of the BOLD
      signal and it seems likely that a disturbed cerebrovascular reserve capacity
      (CVRC) alters the BOLD response. We tested the hypothesis that extra- or
      intracranial artery disease influences the BOLD signal. Twenty-one patients with
      extra- or intracranial stenosis were studied with BOLD sensitive T2*-weighted
      MRI. All patients presented with transient or prolonged reversible ischemic
      symptoms ipsilateral to the artery disease but were asymptomatic at the time
      point of the MRI study. fMRI was performed employing a simple motor task (fist
      closure right and left). Additionally, the CVRC was assessed applying carbogen
      gas during serial T2*-weighted MRI for the calculation of CO(2) reactivity maps
      of the relative signal change. Signal differences between both hemispheres were
      compared in individual subjects and with healthy subjects. Patients with
      disturbed CVRC in the CO(2) reactivity maps showed either a significantly reduced
      (n = 5) or a negative (n = 1) BOLD signal in the affected compared to the
      unaffected primary sensorimotor cortex during fist closure. Patients with intact
      CVRC showed no significant BOLD signal differences between affected and
      unaffected hemisphere. Extra- or intracranial artery disease influences CVRC and
      consequently the BOLD signal. This observation is important for the clinical
      application of fMRI paradigms.

PMID- 14568510
TI  - k-Space based summary motion detection for functional magnetic resonance imaging.
AB  - Functional MRI studies are very sensitive to motion; head movements of as little
      as 1-mm translations or 1 degrees rotations may cause spurious signals. An
      algorithm was developed that uses k-space MRI data to monitor subject motion
      during functional MRI time series. A k-space weighted average of squared
      difference between the initial scan and subsequent scans is calculated, which
      summarizes subject motion in a single quality parameter; however, the quality
      parameter cannot be used for motion correction. The evolution of this quality
      parameter throughout a time series indicates whether head motion is within a
      predetermined limit. Fifty functional MRI studies were used to calibrate the
      sensitivity of the algorithm, using the six rigid-body registration parameters
      (three translations and three rotations) from the statistical parametric mapping
      (SPM99) package as a reference. The average correlation coefficient between the
      new quality parameter and the reference value from SPM was 0.84. The simple
      algorithm correctly classified acceptable or excessive motion with 90% accuracy,
      with the remaining 10% being borderline cases. This method makes it possible to
      evaluate brain motion within seconds after a scan and to decide whether a study
      needs to be repeated.

PMID- 14568511
TI  - Topography and elimination of slow EEG responses related to tongue movements.
AB  - This study aimed to characterize the topography and mechanism of slow EEG
      potentials related to tongue movement (TMP), and to devise a method for their
      elimination. Eight adult subjects were recorded with 8-channel direct current
      (DC) EEG (n = 5) or with a 256-channel, dense array EEG (n = 4). Subjects were
      requested to push their tongue toward the incisors in a closed mouth. We examined
      the time course and topography of the ensuing TMP. The underlying mechanism and
      elimination of TMP were studied by electrical isolation of the tongue with a
      latex sheet, and by short-circuiting of tongue to gingival pouch. Forward
      movement of the tongue caused global changes in scalp potentials, with frontal
      areas more positive, and the strongest gradients between the mastoid region and
      other scalp areas. Scalp current source density was highest near ear canals and
      orbital fossae. Electrical isolation of the tongue tip with a latex sheet
      resulted in a near-complete elimination of TMPs, while short-circuiting resulted
      in high amplitude responses, suggesting that TMPs are caused by a change in the
      geometry of conductive pathways. Our results indicate that significant scalp
      potentials are caused by even modest tongue movements, which may occur
      subconsciously during various cognitive tasks. The topography and small amplitude
      of TMPs make their off-line rejection difficult, while an isolation method of the
      kind used here may substantially diminish TMP artifacts in studies on slow
      cognitive potentials.

PMID- 14568509
TI  - Putting names to faces: successful encoding of associative memories activates the
      anterior hippocampal formation.
AB  - The ability to form associations between previously unrelated items of
      information, such as names and faces, is an essential aspect of episodic memory
      function. The neural substrate that determines success vs. failure in learning
      these associations remains to be elucidated. Using event-related functional MRI
      during the encoding of novel face-name associations, we found that successfully
      remembered face-name pairs showed significantly greater activation in the
      anterior hippocampal formation bilaterally and left inferior prefrontal cortex,
      compared to pairs that were forgotten. Functional connectivity analyses revealed
      significant correlated activity between the right and left hippocampus and
      neocortical regions during successful, but not attempted, encoding. These
      findings suggest that anterior regions of the hippocampal formation, in
      particular, are crucial for successful associative encoding and that the degree
      of coordination between hippocampal and neocortical activity may predict the
      likelihood of subsequent memory.

PMID- 14568513
TI  - Parameter maps of 1H residual dipolar couplings in tendon under mechanical load.
AB  - Proton multipolar spin states associated with dipolar encoded longitudinal
      magnetization (DELM) and double-quantum (DQ) coherences of bound water are
      investigated for bovine and sheep Achilles tendon under mechanical load. DELM
      decay curves and DQ buildup and decay curves reveal changes of the 1H residual
      dipolar couplings for tendon at rest and under local compression forces. The
      multipolar spin states are used to design dipolar contrast filters for NMR 1H
      images of heterogeneous tendon. Heterogeneities in tendon samples were
      artificially generated by local compression parallel and perpendicular to the
      tendon plug axis. Quotient images obtained from DQ-filtered images by matched and
      mismatched excitation/reconversion periods are encoded only by the residual
      dipolar couplings. Semi-quantitative parameter maps of the residual dipolar
      couplings of bound water were obtained from these quotient images using a
      reference elastomer sample. This method can be used to quantify NMR imaging of
      injured ordered tissues.

PMID- 14568512
TI  - Hydrogen bonds lengths in nucleic acids estimated from longitudinal nitrogen-15
      relaxation.
AB  - A new NMR method has been designed for the measurement of the longitudinal
      relaxation rates of both donor and acceptor nitrogen-15 nuclei in Watson-Crick
      base pairs in 15N-enriched nucleic acids. The experiment was applied to a 22
      nucleotide RNA hairpin. The lengths of four hydrogen bonds could be estimated
      from the longitudinal relaxation rates.

PMID- 14568514
TI  - Distance measurements in spin-1/2 systems by 13C and 31P solid-state NMR in dense
      dipolar networks.
AB  - In this article solid-state NMR methods for the determination of internuclear
      dipole-dipole couplings between homonuclear spin-1/2 nuclei are presented. They
      are suitable for relatively dense dipolar networks which are still dominated by 2
      spin interactions. C-/R-symmetry theory is applied to create a double-quantum
      average Hamiltonian using phase-modulated radio-frequency irradiation and magic
      angle sample-rotation. Symmetry derived pulse sequences with improved
      compensation against chemical shift anisotropies were found assuming a small
      isotropic chemical shift difference and using numerical calculations of the spin
      dynamics. Moreover it is shown that a constant time procedure can be used to
      acquire reliable double-quantum build-up curves even in systems in which damping
      obscures oscillations in their symmetric build-up curve. This technique is
      demonstrated on four crystalline model compounds with 31P and 13C spin systems
      typical for inorganic and biological applications. Comparison to crystal
      structure data indicates that the distances derived this way from 31P and 13C
      double-quantum NMR carry only small systematic errors caused for example by
      anisotropic J-coupling, dipolar contributions from adjacent spins and relaxation.

PMID- 14568515
TI  - Quantitative analysis of dinuclear manganese(II) EPR spectra.
AB  - A quantitative method for the analysis of EPR spectra from dinuclear Mn(II)
      complexes is presented. The complex [(Me(3)TACN)(2)Mn(II)(2)(mu-OAc)(3)]BPh(4)
      (1) (Me(3)TACN=N, N('),N(")-trimethyl-1,4,7-triazacyclononane; OAc=acetate(1-);
      BPh(4)=tetraphenylborate(1-)) was studied with EPR spectroscopy at X- and Q-band
      frequencies, for both perpendicular and parallel polarizations of the microwave
      field, and with variable temperature (2-50K). Complex 1 is an
      antiferromagnetically coupled dimer which shows signals from all excited spin
      manifolds, S=1 to 5. The spectra were simulated with diagonalization of the full
      spin Hamiltonian which includes the Zeeman and zero-field splittings of the
      individual manganese sites within the dimer, the exchange and dipolar coupling
      between the two manganese sites of the dimer, and the nuclear hyperfine coupling
      for each manganese ion. All possible transitions for all spin manifolds were
      simulated, with the intensities determined from the calculated probability of
      each transition. In addition, the non-uniform broadening of all resonances was
      quantitatively predicted using a lineshape model based on D- and r-strain. As the
      temperature is increased from 2K, an 11-line hyperfine pattern characteristic of
      dinuclear Mn(II) is first observed from the S=3 manifold. D- and r-strain are the
      dominate broadening effects that determine where the hyperfine pattern will be
      resolved. A single unique parameter set was found to simulate all spectra arising
      for all temperatures, microwave frequencies, and microwave modes. The simulations
      are quantitative, allowing for the first time the determination of species
      concentrations directly from EPR spectra. Thus, this work describes the first
      method for the quantitative characterization of EPR spectra of dinuclear
      manganese centers in model complexes and proteins. The exchange coupling
      parameter J for complex 1 was determined (J=-1.5+/-0.3 cm(-1); H(ex)=
      2JS(1).S(2)) and found to be in agreement with a previous determination from
      magnetization. The phenomenon of exchange striction was found to be insignificant
      for 1.

PMID- 14568516
TI  - Application of the NMR-MOUSE to food emulsions.
AB  - The application of the NMR-MObile Universal Surface Explorer (NMR-MOUSE) to study
      food systems is evaluated using oil-in-water emulsions, and the results are
      compared to those obtained using a conventional low-field NMR (LF-NMR)
      instrument. The NMR-MOUSE is a small and portable LF-NMR system with a one-sided
      magnet layout that is used to replace the conventional magnet and probe on a LF
      NMR instrument. The high magnetic field gradients associated with the one-sided
      MOUSE magnet result in NMR signal decays being dominated by molecular diffusion
      effects, which makes it possible to discriminate between the NMR signals from oil
      and water. Different data acquisition parameters as well as different approaches
      to the analysis of the NMR data from a range of oil-in-water emulsions are
      evaluated, and it is demonstrated how the concentration of oil and water can be
      determined from the NMR-MOUSE signals. From these model systems it is concluded
      that the NMR-MOUSE has good potential for the quantitative analysis of intact
      food products.

PMID- 14568517
TI  - Broadband 13C-13C adiabatic mixing in solution optimized for high fields.
AB  - Experiments which require mixing among spins with large frequency differences are
      generally performed with sequences based on composite pulses or computer
      optimized cycles. Adiabatic pulses generally offer several advantages over other
      approaches, including greater single spin inversion bandwidths and tolerance to
      RF inhomogeneity. Here, a novel theoretical framework is presented in order to
      understand how spin-spin interactions are influenced by adiabatic inversion
      pulses, and insights from this approach are used to design more efficient
      adiabatic coherence exchange experiments. For very large frequency differences,
      this new approach generally offers improved results over previously applied
      mixing sequences, as applied to 13C-13C experiments which are the basis of modern
      sidechain assignment techniques in proteins. It is also anticipated that the
      approach presented here will be applicable to the analysis of various alternative
      approaches to adiabatic mixing.

PMID- 14568518
TI  - Frequency-domain method based on the singular value decomposition for frequency
      selective NMR spectroscopy.
AB  - In several applications of NMR spectroscopy the user is interested only in the
      components lying in a small frequency band of the spectrum. A frequency selective
      analysis deals precisely with this kind of NMR spectroscopy: parameter estimation
      of only those spectroscopic components that lie in a preselected frequency band
      of the NMR data spectrum, with as little interference as possible from the out-of
      band components and in a computationally efficient way. In this paper we
      introduce a frequency-domain singular value decomposition (SVD)-based method for
      frequency selective spectroscopy that is computationally simple, statistically
      accurate, and which has a firm theoretical basis. To illustrate the good
      performance of the proposed method we present a number of numerical examples for
      both simulated and in vitro NMR data.

PMID- 14568519
TI  - Dissection of heteronuclear NMR experiments for studies of magnetization transfer
      efficiencies.
AB  - Modern NMR experiments for applications with biological macromolecules in
      solution typically include multiple magnetization transfer steps. When working
      with large structures, a significant fraction of the magnetization is lost during
      these transfers. For the design and optimization of complex experimental schemes,
      the magnetization transfer efficiencies have therefore commonly been calculated
      from the spin relaxation times. This paper now suggests a new method for
      measurement of individual transfer efficiencies directly with the system of
      interest, using short, reliable experiments. Initial applications of this
      approach with a 110,000 Da protein indicate that there is a wide range of
      transfer efficiencies among individual spin pairs in a structure of this size,
      which leads to a correspondingly large variation of the individual signal
      intensities and the need for techniques to enhance the weak signals.

PMID- 14568520
TI  - Broadband geodesic pulses for three spin systems: time-optimal realization of
      effective trilinear coupling terms and indirect SWAP gates.
AB  - Broadband implementations of time-optimal geodesic pulse elements are introduced
      for the efficient creation of effective trilinear coupling terms for spin systems
      consisting of three weakly coupled spins 1/2. Based on these pulse elements, the
      time-optimal implementation of indirect SWAP operations is demonstrated
      experimentally. The duration of indirect SWAP gates based on broadband geodesic
      sequence is reduced by 42.3% compared to conventional approaches.

PMID- 14568521
TI  - PFG-assisted selection and suppression of 1H NMR signals in the solid state under
      fast MAS.
AB  - Under fast MAS conditions, techniques for 1H signal selection and suppression,
      which have originally been developed for solution-state NMR, become applicable to
      solids. In this work, we describe how WATERGATE and DANTE pulse sequences can be
      used under MAS to selectively excite or suppress peaks in 1H solid-state spectra.
      As known from the liquid-state analogues, signal selection and/or suppression is
      supported by pulsed-field gradients which selectively dephase and rephase
      transverse magnetisation. Under MAS, the required field gradients are provided by
      a simple pair of coils which have been built into a standard fast-MAS probe. PFG
      assisted techniques enable efficient selection or suppression of 1H peaks in a
      single transient of the pulse sequence without the need for phase cycles.
      Therefore, these tools can readily be incorporated into solid-state MAS NMR
      experiments, which is demonstrated here for 1H-1H double-quantum NMR spectra of
      supramolecular systems. In the examples presented here, the 1H signals of
      interest are relatively weak and need to be observed despite the presence of the
      strong 1H signal of long alkyl sidechains. PFG-assisted suppression of this
      strong perturbing signal is shown to be particularly useful for obtaining
      unambiguous results.

PMID- 14568522
TI  - High resolution electron spin resonance microscopy.
AB  - NMR microscopy is routinely employed in fields of science such as biology,
      botany, and materials science to observe magnetic parameters and transport
      phenomena in small scale structures. Despite extensive efforts, the resolution of
      this method is limited (>10 microm for short acquisition times), and thus cannot
      answer many key questions in these fields. We show, through theoretical
      prediction and initial experiments, that ESR microscopy, although much less
      developed, can improve upon the resolution limits of NMR, and successfully
      undertake the 1 mum resolution challenge. Our theoretical predictions demonstrate
      that existing ESR technology, along with advanced imaging probe design (resonator
      and gradient coils), using solutions of narrow linewidth radicals (the trityl
      family), should yield 64 x 64 pixels 2D images (with z slice selection) with a
      resolution of 1 x 1 x 10 microm at approximately 60 GHz in less than 1h of
      acquisition. Our initial imaging results, conducted by CW ESR at X-band, support
      these theoretical predictions and already improve upon the previously reported
      state-of-the-art for 2D ESR image resolution achieving approximately 10 x 10 mum,
      in just several minutes of acquisition time. We analyze how future progress,
      which includes improved resonators, increased frequency of measurement, and
      advanced pulsed techniques, should achieve the goal of micron resolution.

PMID- 14568523
TI  - Electronic g-factor measurement from ENDOR-induced EPR patterns: malonic acid and
      guanine hydrochloride dihydrate.
AB  - Measurement of electronic g-factors (g) from radicals in irradiated organic
      crystals is generally difficult because the overall EPR pattern is usually the
      composite of several components, e.g., from multiple radicals and from multiple
      magnetic sites. However, when an ENDOR line is fully resolved, the method of
      ENDOR-induced EPR (EI-EPR, or EIE) in principle permits identification of the EPR
      pattern from the individual component yielding the line. To examine this method
      as an approach useful for measuring g, we used it to measure those of known
      radicals in two different crystal systems. First, to verify correspondence of the
      EIE and EPR sufficient for using EIE patterns to extract g, we used both EIE and
      EPR to measure g of (*CH(COOH)(2) from irradiated crystals of malonic acid. Then,
      to illustrate the procedure applied to a system giving a more complex EPR
      pattern, we used EIE to measure g of the O6-protonated anion radical of guanine
      in irradiated guanine.HCl.2H(2)O crystals. EPR results from the malonic acid
      radical are g(max)=2.00374(2), g(mid)=2.00331(2), and g(min)=2.00234(3); EIE
      results from the same radical are g(max)=2.00375(2), g(mid)=2.00334(2), and
      g(min)=2.00238(2), where numbers in parentheses indicate statistical
      uncertainties in the respective least significant digits. In addition,
      eigenvectors from the two sets of measurements agree to approximately 1 degrees.
      Results from the guanine radical are g(max)=2.00490(2), g(mid)=2.00318(4), and
      g(min)=2.00218(4). (The uncertainties should reliably indicate relative accuracy,
      while absolute accuracy is within +/-0.0002 as indicated by simultaneous
      measurement of Cr(3+) in MgO.)

PMID- 14568524
TI  - Aqueous flat cells perpendicular to the electric field for use in electron
      paramagnetic resonance spectroscopy.
AB  - An analytic solution of the Maxwell equations for aqueous flat cells in
      rectangular TE(102) cavities has led to the prediction of significant (3-6 times)
      X-band EPR signal improvement over the standard flat cell for a new sample
      configuration consisting of many flat cells oriented perpendicular to the
      electric field nodal plane. Analytic full wave solutions in the presence of
      sample and wall losses have been obtained and numerically evaluated. Observation
      of the predicted fields led to a classification of three distinct types of sample
      loss mechanisms, which, in turn inspired sample designs that minimize each loss
      type. The resulting EPR signal enhancement is due to the presence and centering
      of a tangential electric field node within each individual sample region. Samples
      that saturate with the available RF magnetic field and those that do not are
      considered. Signal enhancement appears in both types. These observations, done
      for the TE(102) mode, carry over to the uniform field (UF) modes, a relatively
      new class of microwave cavities for use in EPR spectroscopy developed in this
      laboratory. Rectangular UF modes have an RF magnetic field magnitude that is
      uniform in a plane. Based on this analysis, a practical multiple flat-cell design
      is proposed.

PMID- 14568525
TI  - Effects of finite-width pulses in the pulsed-field gradient measurement of the
      diffusion coefficient in connected porous media.
AB  - We analytically compute the apparent diffusion coefficient D(app) for an open
      restricted geometry, such as an extended porous medium, for the case of a pulsed
      field gradient (PFG) experiment with finite-width pulses. In the short- and long
      time limits, we give explicit, model-independent expressions that correct for the
      finite duration of the pulses and can be used to extract the pore surface-to
      volume (S/V) ratio as well as the tortuosity. For all times, we compute D(app)
      using a well-established model form of the actual time-dependent diffusion
      coefficient D(t) that can be obtained from an ideal narrow-pulse PFG. We compare
      D(app) and D(t) and find that, regardless of pulse widths and geometry-dependent
      parameters, the two quantities deviate by less than 20%. These results are in
      sharp contrast with the studies on closed geometries [J. Magn. Reson. A 117
      (1995) 209], where the effects of finite gradient-pulse widths are large. The
      analytical results presented here can be easily adapted for different pulse
      protocols and time sequences.

PMID- 14568527
TI  - Low field intermolecular double-quantum coherence imaging via the Overhauser
      effect.
AB  - Intermolecular double-quantum coherence (i-DQC) signals in liquids are usually
      associated with high magnetic fields. We demonstrate that, in a magnetic field of
      only 16mT, i-DQC imaging of water protons is feasible thanks to the nuclear
      magnetization enhancement produced by the Overhauser effect. i-DQC images of a
      phantom containing an aqueous solution of a trityl free radical, with phase
      encoding in the DQC evolution period or in the acquisition period, are presented.
      Possible applications of low field i-MQC images are proposed.

PMID- 14568526
TI  - Preparation of protein nanocrystals and their characterization by solid state
      NMR.
AB  - Preparation of proteins in their crystalline state has been found to be important
      in producing stable therapeutic protein formulations, cross-linked enzyme
      crystals for application in industrial processes, generating novel porous media
      for separations, and of course in structure elucidation. Of these applications
      only X-ray crystallography requires large crystals, defined here as being
      crystals 100s of microns or greater in size. Smaller crystals have attractive
      attributes in many instances, and are just as useful in structure determination
      by solid state NMR (ssNMR) as are large crystals. In this paper we outline a
      simple set of procedures for preparing nanocrystalline protein samples for ssNMR
      or other applications and describe the characterization of their crystallinity by
      ssNMR and X-ray powder diffraction. The approach is demonstrated in application
      to five different proteins: ubiquitin, lysozyme, ribonuclease A, streptavidin,
      and cytochrome c. In all instances the nanocrystals produced are found to be
      highly crystalline as judged by natural abundance 13C ssNMR and optical and
      electron microscopy. We show for ubiquitin that nanocrystals prepared by rapid
      batch crystallization yield equivalent 13C ssNMR spectra to those of larger X-ray
      diffraction quality crystals. Single crystal and powder X-ray diffraction
      measurements are made to compare the degree of order present in polycrystalline,
      nanocrystalline, and lyophilized ubiquitin. Solid state 13C NMR is also used to
      show that ubiquitin nanocrystals are thermally robust, giving no indication of
      loss of local order after repeated temperature cycling between liquid nitrogen
      and room temperature. The methods developed are rapid and should scale well from
      the tenths of milligram to multi-gram scales, and as such should find wide
      utility in the preparation of protein nanocrystals for applications in catalysis,
      separations, and especially in sample preparation for structural studies using
      ssNMR.

PMID- 14568528
TI  - An application of the XiX decoupling for solid state 13C NMR with mobile samples.
AB  - It is very important to obtain higher resolution solid state NMR spectra not only
      for crystal samples but also for mobile solid samples. We demonstrate that a
      robust proton decoupling technique, XiX (X inverse-X) decoupling, is very
      effective in high resolution solid state NMR measurement for mobile samples
      compared with the usual continuous wave proton decoupling.

PMID- 14568529
TI  - A tetramer-octamer equilibrium in Mycobacterium leprae and Escherichia coli RuvA
      by analytical ultracentrifugation.
AB  - In the context of the bacterial RuvABC system, RuvA protein binds to and is
      involved in the subsequent processing of a four-way DNA structure called Holliday
      junction that is formed during homologous recombination. Four crystal structures
      of RuvA from Escherichia coli (EcoRuvA) showed that it was tetrameric, while
      neutron scattering and two other crystal structures for RuvA from Mycobacterium
      leprae (MleRuvA) and EcoRuvA showed that it was an octamer. To clarify this
      discrepancy, sedimentation equilibrium experiments by analytical
      ultracentrifugation were carried out and the results showed that MleRuvA existed
      as a tetramer-octamer equilibrium between 0.2-0.5 mg/ml in 0.1 M NaCl with a
      dissociation constant of 4 muM, and is octameric at higher concentrations. The
      same experiments in 0.3 M NaCl showed that MleRuvA is a tetramer up to 3.5 mg/ml,
      indicating that salt bridges are involved in octamer formation. Sedimentation
      equilibrium experiments with EcoRuvA showed that it was tetrameric at low
      concentration in both salt buffers but the protein was insoluble at high-protein
      concentrations in 0.1 M NaCl. It is concluded that free RuvA exists in an
      equilibrium between tetrameric and octameric forms in the typical concentration
      range and buffer found in bacterial cells.

PMID- 14568530
TI  - A metal-ligand-mediated intersubunit allosteric switch in related SmtB/ArsR zinc
      sensor proteins.
AB  - The origin of metal ion selectivity by members of the SmtB/ArsR family of
      bacterial metal-sensing transcriptional repressors and the mechanism of negative
      allosteric regulation of DNA binding is poorly understood. Here, we report that
      two homologous zinc sensors, Staphylococcus aureus CzrA and cyanobacterial SmtB,
      are "winged" helix homodimeric DNA-binding proteins that bind Zn(II) to a pair of
      tetrahedral, interhelical binding sites, with two ligands derived from the alpha5
      helix of one subunit, Asp84 O(delta1) (Asp104 in SmtB), His86 N(delta1) (His106),
      and two derived from the alpha5 helix of the other, His97' N(delta1) (His117')
      and His100' N(epsilon2) (Glu120'). Formation of the metal chelate drives a
      quaternary structural switch mediated by an intersubunit hydrogen-binding network
      that originates with the non-liganding N(epsilon2) face of His97 in CzrA (His117
      in SmtB) that stabilizes a low-affinity, DNA-binding conformation. The structure
      of the Zn(1) SmtB homodimer shows that both metal-binding sites of the dimer must
      be occupied for the quaternary structural switch to occur. Thus, a critical zinc
      ligating histidine residue obligatorily couples formation of the metal-sensing
      coordination chelate to changes in the conformation and dynamics of the putative
      DNA-binding helices.

PMID- 14568531
TI  - Interactions of yeast ribosomal protein rpS14 with RNA.
AB  - Yeast ribosomal protein S14 (rpS14) binds to two different RNA molecules: (1).
      helix 23 of 18S rRNA during its assembly into 40S ribosomal subunits and (2). a
      stem-loop structure in RPS14B pre-mRNA to repress expression of the RPS14B gene.
      We used the three-dimensional structure of Thermus thermophilus ribosomal protein
      S11, a bacterial homologue of rpS14, as a guide to identify conserved, surface
      exposed amino acid residues that are likely to contact RNA. Eight residues that
      met these criteria were mutated to alanine. Most of these mutations affected
      interaction of rpS14 with either helix 23 or the RPS14B stem-loop RNA or both.
      Assembly of 40S ribosomal subunits and repression of RPS14B were also affected.
      S11 contains an extended carboxy-terminal domain rich in basic amino acids, which
      interacts with rRNA. We systematically evaluated the importance of each of the
      last ten amino acid residues in the basic, carboxy-terminal tail of yeast rpS14
      for binding to RNA, by mutating each to alanine. Mutations in nine of these
      residues decreased binding of rpS14 to one or both of its RNA ligands. In
      addition, we examined the importance of four structural motifs in helix 23 of 18S
      rRNA for binding to rpS14. Mutations that altered either the terminal loop, the G
      U base-pair closing the terminal loop, or the internal loop affected binding of
      rpS14 to helix 23.

PMID- 14568532
TI  - Solution structural study of BlaI: implications for the repression of genes
      involved in beta-lactam antibiotic resistance.
AB  - beta-Lactamase and penicillin-binding protein PBP2' mediate staphylococcal
      resistance to beta-lactam antibiotics, which are otherwise highly clinically
      effective. Two repressors (BlaI and MecI) regulate expression of these inducible
      proteins. Here, we present the first solution structure of the 82 amino acid
      residue DNA-binding domain of Bacillus licheniformis BlaI which is very similar
      in primary sequence to the medically significant Staphyloccocal BlaI and MecI
      proteins. This structure is composed of a compact core of three alpha-helices and
      a three-stranded beta-sheet typical of the winged helix protein (WHP) family. The
      protein/DNA complex was studied by NMR chemical shift comparison between the free
      and complexed forms of BlaI. Residues involved in DNA interaction were identified
      and a WHP canonical model of interaction with the operators is proposed. In this
      model, specific contacts occur between the base-pairs of the TACA motif and
      conserved amino acid residues of the repressor helix H3. These results help
      toward understanding the repression and induction mechanism of the genes coding
      for beta-lactamase and PBP2'.

PMID- 14568533
TI  - Optimal determination of particle orientation, absolute hand, and contrast loss
      in single-particle electron cryomicroscopy.
AB  - A computational procedure is described for assigning the absolute hand of the
      structure of a protein or assembly determined by single-particle electron
      microscopy. The procedure requires a pair of micrographs of the same particle
      field recorded at two tilt angles of a single tilt-axis specimen holder together
      with the three-dimensional map whose hand is being determined. For orientations
      determined from particles on one micrograph using the map, the agreement (average
      phase residual) between particle images on the second micrograph and map
      projections is determined for all possible choices of tilt angle and axis.
      Whether the agreement is better at the known tilt angle and axis of the
      microscope or its inverse indicates whether the map is of correct or incorrect
      hand. An increased discrimination of correct from incorrect hand (free hand
      difference), as well as accurate identification of the known values for the tilt
      angle and axis, can be used as targets for rapidly optimizing the search or
      refinement procedures used to determine particle orientations. Optimized
      refinement reduces the tendency for the model to match noise in a single image,
      thus improving the accuracy of the orientation determination and therefore the
      quality of the resulting map. The hand determination and refinement optimization
      procedure is applied to image pairs of the dihydrolipoyl acetyltransferase (E2)
      catalytic core of the pyruvate dehydrogenase complex from Bacillus
      stearothermophilus taken by low-dose electron cryomicroscopy. Structure factor
      amplitudes of a three-dimensional map of the E2 catalytic core obtained by
      averaging untilted images of 3667 icosahedral particles are compared to a
      scattering reference using a Guinier plot. A noise-dependent structure factor
      weight is derived and used in conjunction with a temperature factor (B=-1000A(2))
      to restore high-resolution contrast without amplifying noise and to visualize
      molecular features to 8.7A resolution, according to a new objective criterion for
      resolution assessment proposed here.

PMID- 14568534
TI  - 2.0A resolution crystal structures of the ternary complexes of human
      phenylalanine hydroxylase catalytic domain with tetrahydrobiopterin and 3-(2
      thienyl)-L-alanine or L-norleucine: substrate specificity and molecular motions
      related to substrate binding.
AB  - The crystal structures of the catalytic domain of human phenylalanine hydroxylase
      (hPheOH) in complex with the physiological cofactor 6(R)-L-erythro-5,6,7,8
      tetrahydrobiopterin (BH(4)) and the substrate analogues 3-(2-thienyl)-L-alanine
      (THA) or L-norleucine (NLE) have been determined at 2.0A resolution. The ternary
      THA complex confirms a previous 2.5A structure, and the ternary NLE complex shows
      that similar large conformational changes occur on binding of NLE as those
      observed for THA. Both structures demonstrate that substrate binding triggers
      structural changes throughout the entire protomer, including the displacement of
      Tyr138 from a surface position to a buried position at the active site, with a
      maximum displacement of 20.7A for its hydroxyl group. Two hinge-bending regions,
      centred at Leu197 and Asn223, act in consort upon substrate binding to create
      further large structural changes for parts of the C terminus. Thus, THA/L-Phe
      binding to the active site is likely to represent the epicentre of the global
      conformational changes observed in the full-length tetrameric enzyme. The
      carboxyl and amino groups of THA and NLE are positioned identically in the two
      structures, supporting the conclusion that these groups are of key importance in
      substrate binding, thus explaining the broad non-physiological substrate
      specificity observed for artificially activated forms of the enzyme. However, the
      specific activity with NLE as the substrate was only about 5% of that with THA,
      which is explained by the different affinities of binding and different catalytic
      turnover.

PMID- 14568535
TI  - Clostridium absonum alpha-toxin: new insights into clostridial phospholipase C
      substrate binding and specificity.
AB  - Clostridium absonum phospholipase C (Caa) is a 42.7 kDa protein, which shows 60%
      amino acid sequence identity with the Clostridium perfringens phospholipase C, or
      alpha-toxin (Cpa), and has been isolated from patients suffering from gas
      gangrene. We report the cloning and sequencing, purification, characterisation
      and crystal structure of the Caa enzyme. Caa had twice the phospholipid
      hydrolysing (lecithinase) activity, 1.5 times the haemolytic activity and over
      seven times the activity towards phosphatidylcholine-based liposomes when
      compared with Cpa. However, the Caa enzyme had a lower activity than Cpa to the
      free (i.e. not in lipid bilayer) substrate para-nitrophenylphosphorylcholine,
      towards sphingomyelin-based liposomes and showed half the cytotoxicity. The
      lethal dose (LD(50)) of Caa in mice was approximately twice that of Cpa. The
      crystal structure of Caa shows that the 72-93 residue loop is in a conformation
      different from those of previously determined open-form alpha-toxin structures.
      This conformational change suggests a role for W84 in membrane binding and a
      possible route of entry into the active site along a hydrophobic channel created
      by the re-arrangement of this loop. Overall, the properties of Caa are compatible
      with a role as a virulence-determinant in gas gangrene caused by C.absonum.

PMID- 14568536
TI  - Three-dimensional structure of a monomeric form of a retroviral protease.
AB  - The assembly of Mason-Pfizer monkey virus Gag polyproteins into immature capsids
      and their cleavage by the encoded protease are temporally and spatially separated
      processes, making the virus a particularly useful model for investigation of
      protease activation. Here we present a high resolution NMR structure of a fully
      folded monomer of a 12 kDa M-PMV protease (wt 12 PR) and of a
      Cys7Ala/Asp26Asn/Cys106Ala mutant (12 PR(D26N/C7A/C106A)). The overall structures
      of both wt 12 PR and 12 PR(D26N/C7A/C106A) follow the conservative structural
      motif of other retroviral proteases. The most prominent difference from the
      canonical fold of retroviral proteases is the absence of the interfacial beta
      sheet, which leads to the loss of the principal force stabilizing the dimer of M
      PMV PR. The monomer-dimer equilibrium can be shifted in favor of the dimer by
      adding a substrate or an inhibitor, partially compensating for the missing role
      of the beta-sheet. We also show that cysteines C7 and C106 play a crucial role in
      stabilizing the dimer and consequently increasing the proteolytic activity of M
      PMV PR. This is consistent with the role of reversible oxidative modification of
      the cysteine residues in the regulation of the maturation of assembled M-PMV
      capsids in the cytoplasm.

PMID- 14568537
TI  - Evolution and classification of P-loop kinases and related proteins.
AB  - Sequences and structures of all P-loop-fold proteins were compared with the aim
      of reconstructing the principal events in the evolution of P-loop-containing
      kinases. It is shown that kinases and some related proteins comprise a
      monophyletic assemblage within the P-loop NTPase fold. An evolutionary
      classification of these proteins was developed using standard phylogenetic
      methods, analysis of shared sequence and structural signatures, and similarity
      based clustering. This analysis resulted in the identification of approximately
      40 distinct protein families within the P-loop kinase class. Most of these
      enzymes phosphorylate nucleosides and nucleotides, as well as sugars, coenzyme
      precursors, adenosine 5'-phosphosulfate and polynucleotides. In addition, the
      class includes sulfotransferases, amide bond ligases, pyrimidine and
      dihydrofolate reductases, and several other families of enzymes that have
      acquired new catalytic capabilities distinct from the ancestral kinase reaction.
      Our reconstruction of the early history of the P-loop NTPase fold includes the
      initial split into the common ancestor of the kinase and the GTPase classes, and
      the common ancestor of ATPases. This was followed by the divergence of the
      kinases, which primarily phosphorylated nucleoside monophosphates (NMP), but
      could have had broader specificity. We provide evidence for the presence of at
      least two to four distinct P-loop kinases, including distinct forms specific for
      dNMP and rNMP, and related enzymes in the last universal common ancestor of all
      extant life forms. Subsequent evolution of kinases seems to have been dominated
      by the emergence of new bacterial and, to a lesser extent, archaeal families.
      Some of these enzymes retained their kinase activity but evolved new substrate
      specificities, whereas others acquired new activities, such as sulfate transfer
      and reduction. Eukaryotes appear to have acquired most of their kinases via
      horizontal gene transfer from Bacteria, partly from the mitochondrial and
      chloroplast endosymbionts and partly at later stages of evolution. A distinct
      superfamily of kinases, which we designated DxTN after its sequence signature,
      appears to have evolved in selfish replicons, such as bacteriophages, and was
      subsequently widely recruited by eukaryotes for multiple functions related to
      nucleic acid processing and general metabolism. In the course of this analysis,
      several previously undetected groups of predicted kinases were identified,
      including widespread archaeo-eukaryotic and archaeal families. The results could
      serve as a framework for systematic experimental characterization of new
      biochemical and biological functions of kinases.

PMID- 14568538
TI  - Engineering the exo-loop of Trichoderma reesei cellobiohydrolase, Cel7A. A
      comparison with Phanerochaete chrysosporium Cel7D.
AB  - The exo-loop of Trichoderma reesei cellobiohydrolase Cel7A forms the roof of the
      active site tunnel at the catalytic centre. Mutants were designed to study the
      role of this loop in crystalline cellulose degradation. A hydrogen bond to
      substrate made by a tyrosine at the tip of the loop was removed by the Y247F
      mutation. The mobility of the loop was reduced by introducing a new disulphide
      bridge in the mutant D241C/D249C. The tip of the loop was deleted in mutant
      Delta(G245-Y252). No major structural disturbances were observed in the mutant
      enzymes, nor was the thermostability of the enzyme affected by the mutations. The
      Y247F mutation caused a slight k(cat) reduction on 4-nitrophenyl lactoside, but
      only a small effect on cellulose hydrolysis. Deletion of the tip of the loop
      increased both k(cat) and K(M) and gave reduced product inhibition. Increased
      activity was observed on amorphous cellulose, while only half the original
      activity remained on crystalline cellulose. Stabilisation of the exo-loop by the
      disulphide bridge enhanced the activity on both amorphous and crystalline
      cellulose. The ratio Glc(2)/(Glc(3)+Glc(1)) released from cellulose, which is
      indicative of processive action, was highest with Tr Cel7A wild-type enzyme and
      smallest with the deletion mutant on both substrates. Based on these data it
      seems that the exo-loop of Tr Cel7A has evolved to facilitate processive
      crystalline cellulose degradation, which does not require significant
      conformational changes of this loop.

PMID- 14568539
TI  - A novel binding protein for a member of CyP40-type Cyclophilins: N.crassa
      CyPBP37, a growth and thiamine regulated protein homolog to yeast Thi4p.
AB  - Cyclophilins belong to the family of peptidyl-prolyl cis/trans isomerases
      (PPIases), which are ubiquitous and highly conserved enzymes capable of cis/trans
      isomerizing Xaa-Pro peptide bonds. Members of the CyP40-type cyclophilins have
      originally been described as components of hormone receptor complexes. Here, we
      describe NcCyP41, a CyP40 ortholog from Neurospora crassa, its expression in
      Escherichia coli and subsequent purification. Characterization of NcCyP41 reveals
      that it is a heat shock protein, which is active as a cyclosporin A-sensitive
      PPIase. Affinity chromatography using immobilized recombinant NcCyP41 yielded two
      major NcCyP41-binding proteins: Hsp80 (a Hsp90 ortholog from N.crassa) and
      CyPBP37. CyPBP37 has not been described. In addition, this is the first record
      describing an interaction between a member of Cyp40-type cyclophilins and of
      CyPBP37-type proteins, respectively. CyPBP37 expression is repressed by thiamine
      and in the stationary phase in N.crassa. CyPBP37 is present in different
      isoforms. The expression of a CyPBP37 ortholog in yeast, Thi4p, is diminished in
      a mutant lacking one of the two CyP40 orthologs (Cpr7p). In addition, the
      DeltaCpr7p deletion mutant shows a thiamine-dependent growth defect. We conclude
      that, in yeast, Cpr7p and Thi4p interact functionally.

PMID- 14568540
TI  - Structural consequences of accommodation of four non-cognate amino acid residues
      in the S1 pocket of bovine trypsin and chymotrypsin.
AB  - Crystal structures of P1 Gly, Val, Leu and Phe bovine pancreatic trypsin
      inhibitor (BPTI) variants in complex with two serine proteinases, bovine trypsin
      and chymotrypsin, have been determined. The association constants for the four
      mutants with the two enzymes show that the enlargement of the volume of the P1
      residue is accompanied by an increase of the binding energy, which is more
      pronounced for bovine chymotrypsin. Since the conformation of the P1 side-chains
      in the two S1 pockets is very similar, we suggest that the difference in DeltaG
      values between the enzymes must arise from the more polar environment of the S1
      site of trypsin. This results mainly from the substitutions of Met192 and Ser189
      observed in chymotrypsin with Gln192 and Asp189 present in trypsin. The more
      polar interior of the S1 site of trypsin is reflected by a much higher order of
      the solvent network in the empty pocket of the enzyme, as is observed in the
      complexes of the two enzymes with the P1 Gly BPTI variant. The more optimal
      binding of the large hydrophobic P1 residues by chymotrypsin is also reflected by
      shrinkage of the S1 pocket upon the accommodation of the cognate residues of this
      enzyme. Conversely, the S1 pocket of trypsin expands upon binding of such side
      chains, possibly to avoid interaction with the polar residues of the walls.
      Further differentiation between the two enzymes is achieved by small differences
      in the shape of the S1 sites, resulting in an unequal steric hindrance of some of
      the side-chains, as observed for the gamma-branched P1 Leu variant of BPTI, which
      is much more favored by bovine chymotrypsin than trypsin. Analysis of the
      discrimination of beta-branched residues by trypsin and chymotrypsin is based on
      the complexes with the P1 Val BPTI variant. Steric repulsion of the P1 Val
      residue by the walls of the S1 pocket of both enzymes prevents the P1 Val side
      chain from adopting the most optimal chi1 value.

PMID- 14568541
TI  - How well is enzyme function conserved as a function of pairwise sequence
      identity?
AB  - Enzyme function conservation has been used to derive the threshold of sequence
      identity necessary to transfer function from a protein of known function to an
      unknown protein. Using pairwise sequence comparison, several studies suggested
      that when the sequence identity is above 40%, enzyme function is well conserved.
      In contrast, Rost argued that because of database bias, the results from such
      simple pairwise comparisons might be misleading. Thus, by grouping enzyme
      sequences into families based on sequence similarity and selecting representative
      sequences for comparison, he showed that enzyme function starts to diverge
      quickly when the sequence identity is below 70%. Here, we employ a strategy
      similar to Rost's to reduce the database bias; however, we classify enzyme
      families based not only on sequence similarity, but also on functional
      similarity, i.e. sequences in each family must have the same four digits or the
      same first three digits of the enzyme commission (EC) number. Furthermore,
      instead of selecting representative sequences for comparison, we calculate the
      function conservation of each enzyme family and then average the degree of enzyme
      function conservation across all enzyme families. Our analysis suggests that for
      functional transferability, 40% sequence identity can still be used as a
      confident threshold to transfer the first three digits of an EC number; however,
      to transfer all four digits of an EC number, above 60% sequence identity is
      needed to have at least 90% accuracy. Moreover, when PSI-BLAST is used, the
      magnitude of the E-value is found to be weakly correlated with the extent of
      enzyme function conservation in the third iteration of PSI-BLAST. As a result,
      functional annotation based on the E-values from PSI-BLAST should be used with
      caution. We also show that by employing an enzyme family-specific sequence
      identity threshold above which 100% functional conservation is required,
      functional inference of unknown sequences can be accurately accomplished.
      However, this comes at a cost: those true positive sequences below this threshold
      cannot be uniquely identified.

PMID- 14568542
TI  - Motor axon migration: a long way to go.
AB  - Coordinated motor behaviors rely on a maze-like network of axonal connections
      between motoneurons and the body musculature. Since the time of the Renaissance,
      scientists have been fascinated by the question of how such complex, yet
      stereotypic, connectivity arises during embryogenesis. Here, we review the long
      journey of motor axons, which traverse diverse territories along predetermined
      routes riddled with a wealth of divergent pathway options. We conclude that motor
      axon migration occurs in a stepwise manner, with each step being controlled by
      local guidance cues, that motor axons rely on some of the same cues that also
      control axon migration within the CNS, and that, due to species-specific
      anatomical variations, the cell types providing such local cues may vary.
      Although studies of motor axon migration have not yet resulted in a complete
      understanding of the cellular and molecular mechanisms regulating this process,
      we have come a long way since the days of da Vinci.

PMID- 14568543
TI  - Interplay of negative and positive signals controls endoderm-specific expression
      of the ascidian Cititf1 gene promoter.
AB  - Cititf1 is an early and specific marker of endoderm development in Ciona
      intestinalis [ Development 126, 5149]. Here, we examine Cititf1 transcriptional
      regulation focusing in particular on its endodermal restricted expression.
      Through the analysis of Ciona embryos, electroporated with different portions of
      Cititf1 5'-flanking region fused to lacZ, we characterized a minimal 300-bp cis
      regulatory sequence able to closely reproduce the spatial and temporal expression
      pattern of the endogenous gene. This enhancer contains at least three distinct
      regulatory regions, two of which are responsible for activation of transcription
      in the endoderm and in the mesenchyme, respectively, while the third is a
      negative control element that represses mesenchyme transcription. We have further
      defined the sequences responsible for transcriptional activation in the endoderm
      by clustered point mutations and DNA-binding assays.

PMID- 14568544
TI  - Fibroblast growth factors redirect retinal axons in vitro and in vivo.
AB  - Growth factors have been shown previously to participate in the process of axon
      target recognition. We showed that fibroblast growth factor receptor (FGFR)
      signaling is required for Xenopus laevis retinal ganglion cell (RGC) axons to
      recognize their major midbrain target, the optic tectum [neuron 17 (1996), 245].
      Therefore, we have hypothesized that a change in expression of a fibroblast
      growth factor (FGF) at the entrance of the optic tectum, the border between the
      diencephalon and mesencephalon, may serve as a signal to RGC axons that they have
      reached their target. To determine whether RGC axons can sense changes in FGF
      levels, we asked whether they altered their behavior upon encountering an ectopic
      source of FGF. We found that in vivo RGC growth cones avoided FGF-misexpressing
      cells along their path, and that FGF-2 directly repelled RGC growth cones in an
      in vitro growth cone turning assay. These data support the idea that RGC axons
      can sense changes in FGF levels, and as such provide a mechanism by which FGFR
      signaling is involved in RGC axon target recognition.

PMID- 14568545
TI  - Endodermal growth factors promote endocardial precursor cell formation from
      precardiac mesoderm.
AB  - We previously demonstrated that the initial emergence of endocardial precursor
      cells (endocardial angioblasts) occurred within the precardiac mesoderm and that
      the endodermal secretory products promoted delamination of cells from the
      precardiac mesoderm and expression of endothelial lineage markers [Dev. Biol. 175
      (1996), 66]. In this study, we sought to extend our original study to the
      identification of candidate molecules derived from the endoderm that might have
      induced endocardial precursor cell formation. We have detected expression of
      transforming growth factors beta (TGFbeta) 2, 3, and 4 in anterior endoderm at
      Hamburger and Hamilton (H-H) stage 5 by RT-PCR. To address the role of growth
      factors known to be present in the endoderm, precardiac mesodermal explants were
      isolated from H-H stage 5 quail embryos and cultured on the surface of collagen
      gels with serum-free defined medium 199. Similar to the effect of explants
      cocultured with anterior endoderm, when cultured with TGFbetas 1-3 (3 ng/ml
      each), explants formed QH-1 (anti-quail endothelial marker)-positive mesenchymal
      cells, which invaded the gel and expressed the extracellular marker, cytotactin
      (tenascin). Another member of the TGFbeta superfamily, bone morphogenetic protein
      2 (BMP-2; 100 ng/ml), did not induce QH-1-positive mesenchymal cell formation but
      promoted formation of an epithelial monolayer on the surface of the collagen gel;
      this monolayer did not express QH-1. Explants treated with vascular endothelial
      growth factor (VEGF(165), 100 ng/ml) also did not invade the gel but formed an
      epithelial-like outgrowth on the surface of the gel. However, this monolayer did
      express the QH-1 marker. Fibroblast growth factor-2 (FGF-2; 250 ng/ml)-treated
      explants expressed QH-1 and exhibited separation of the cells on the surface of
      the gel. Finally, a combination of TGFbetas and VEGF enhanced formation of QH-1
      positive cord-like structures within the gel from mesenchyme that had previously
      invaded the gel. Luminization of the cords, however, was not clearly evident.
      These findings suggest that TGFbetas, among the growth factors tested, mediate
      the initial step of endocardial formation, i.e., delamination of endothelial
      precursor cells from precardiac mesoderm, whereas VEGF may primarily effect early
      vasculogenesis (cord-like structure formation).

PMID- 14568546
TI  - Medulloblastoma tumorigenesis diverges from cerebellar granule cell
      differentiation in patched heterozygous mice.
AB  - Medulloblastoma is a cerebellar tumor that can arise through aberrant activation
      of Sonic hedgehog (Shh) signaling, which normally regulates cerebellar granule
      cell proliferation. Mutations of the Shh receptor PATCHED (PTCH) are associated
      with medulloblastomas, which have not been found to have loss of PTCH
      heterozygosity. We address whether patched (Ptc) heterozygosity fundamentally
      alters granule cell differentiation and contributes to tumorigenesis by
      increasing proliferation and/or decreasing apoptosis in Ptc+/- mice. Our data
      show that postnatal Ptc+/- mouse granule cell precursor growth is not globally
      altered. However, many older Ptc+/- mice display abnormal cerebellar regions
      containing persistently proliferating granule cell precursors. Since fewer Ptc+/-
      mice form medulloblastomas, these granule cell rests represent a developmentally
      disrupted, but uncommitted stage of tumorigenesis. Although Ptc+/- mouse
      medulloblastomas express neurodevelopmental genes, they diverge from granule cell
      differentiation in their discordant coexpression of postmitotic markers despite
      their ongoing growth. Like human medulloblastomas, mouse tumors with reduced
      levels of the neurotrophin-3 receptor, trkC/Ntrk3, display decreased apoptosis in
      vivo, illustrating the role of TrkC in regulating tumor cell survival. These
      results indicate that Ptc heterozygosity contributes to tumorigenesis by
      predisposing a subset of granule cell precursors to the formation of
      proliferative rests and subsequent dysregulation of developmental gene
      expression.

PMID- 14568547
TI  - Zebrafish hhex, nk2.1a, and pax2.1 regulate thyroid growth and differentiation
      downstream of Nodal-dependent transcription factors.
AB  - During zebrafish development, the thyroid primordium initiates expression of
      molecular markers such as hhex and nk2.1a in the endoderm prior to pharynx
      formation. As expected for an endodermally derived organ, initiation of thyroid
      development depends on Nodal signalling. We find that it also depends on three
      downstream effectors of Nodal activity, casanova (cas), bonnie and clyde (bon),
      and faust (fau)/gata5. Despite their early Nodal-dependent expression in the
      endoderm, both hhex and nk2.1a are only required relatively late during thyroid
      development. In hhex and nk2.1a loss-of-function phenotypes, thyroid development
      is initiated and arrests only after the primordium has evaginated from the
      pharyngeal epithelium. Thus, like pax2.1, both hhex and nk2.1a have similarly
      late roles in differentiation or growth of thyroid follicular cells, and here, we
      show that all three genes act in parallel rather than in a single pathway. Our
      functional analysis suggests that these genes have similar roles as in mammalian
      thyroid development, albeit in a different temporal mode of organogenesis.

PMID- 14568549
TI  - Antagonistic relationship between Dpp and EGFR signaling in Drosophila head
      patterning.
AB  - The Drosophila eye field that gives rise to the visual system and dorsal head
      epidermis forms an unpaired anlage located in the dorsal head ectoderm. The eye
      field expresses and requires both Dpp and EGFR signaling for its development. As
      shown in previous studies, EGFR is required for cell maintenance in the
      developing visual system. Dpp initially switches on the early eye genes so and
      eya in the eye field. Consecutively, high levels of Dpp in the dorsal midline
      inhibit these genes and promote development of head epidermis. We show that Dpp
      negatively regulates EGFR signaling, thereby increasing the amount of cell death
      in the dorsal midline. By this mechanism, Dpp controls the formation of a
      bilateral visual system and indirectly modulates cell death, which is essential
      for normal head morphogenesis. Loss of either Dpp or its downstream target, Zen,
      abolishes head epidermis fate and leads to the misexpression of dp-ERK in the
      dorsal midline. The resulting morphological phenotype consists of cyclopia,
      reduction of cell death, and failure of head involution. Ectopic expression of
      activated EGFR inhibits the Dpp target race and thereby causes cyclopia and
      defective head involution. We discuss possible mechanisms of Dpp and EGFR
      interaction in the embryo.

PMID- 14568550
TI  - Human cytotrophoblasts promote endothelial survival and vascular remodeling
      through secretion of Ang2, PlGF, and VEGF-C.
AB  - Cytotrophoblasts are specialized epithelial cells of the human placenta that
      differentiate to acquire tumor-like properties that allow them to invade the
      uterus. Concurrently, they develop endothelial-like characteristics. This
      transformation allows cytotrophoblasts to replace the maternal cells that line
      uterine vessels, thereby diverting maternal blood to the placenta. Previously, we
      showed that invading cytotrophoblasts secrete VEGF-C and PlGF, factors that
      regulate their acquisition of an endothelial-like phenotype. Here, we examined
      the cells' expression of angiopoietin ligands and their Tie receptors. The data
      show that cytotrophoblasts predominantly expressed Ang2. We also studied the
      paracrine functions of Ang2 and the VEGFs by culturing uterine microvascular
      endothelial cells in cytotrophoblast-conditioned medium, which supported their
      growth. Removal of VEGF-C, PlGF, and/or Ang2 from the medium caused a marked
      reduction in cell number due to massive apoptosis. We also assayed the angiogenic
      potential of cytotrophoblast-derived factors in the chick chorioallantoic
      membrane assay. The results showed that they stimulated angiogenesis to a level
      comparable to that of basic FGF. These data suggest that invasive human
      cytotrophoblasts use an unusual repertoire of factors to influence the angiogenic
      state of maternal blood vessels and that this cross talk plays an important part
      in the endovascular component of uterine invasion.

PMID- 14568548
TI  - LIM homeobox gene-dependent expression of biogenic amine receptors in restricted
      regions of the C. elegans nervous system.
AB  - Biogenic amines regulate a variety of behaviors. Their functions are
      predominantly mediated through G-protein-coupled 7-transmembrane domain receptors
      (GPCR), 16 of which are predicted to exist in the genome sequence of the nematode
      Caenorhabditis elegans. We describe here the expression pattern of several of
      these aminergic receptors, including two serotonin receptors (ser-1 and ser-4),
      one tyramine receptor (ser-2), and two dopamine receptors (dop-1 and dop-2).
      Moreover, we describe distinct but partially overlapping expression patterns of
      different splice forms of the ser-2 tyramine receptor locus. We find that each of
      the aminergic receptor genes is expressed in restricted regions of the nervous
      system and that many of them reveal significant overlap with the expression of
      regulatory factors of the LIM homeobox (Lhx) gene family. We demonstrate that the
      expression of several of the biogenic amine receptors is abrogated in specific
      cell types in Lhx gene mutants, thus establishing a role for these Lhx genes in
      regulating aspects of neurotransmission. We extend these findings with other cell
      fate markers and show that the lim-4 Lhx gene is required for several but not all
      aspects of RID motor neuron differentiation and that the lim-6 Lhx gene is
      required for specific aspects of RIS interneuron differentiation. We also use
      aminergic receptor gfp reporter fusions as tools to visualize the anatomy of
      specific neurons in Lhx mutant backgrounds and find that the development of the
      elaborate dendritic branching pattern of the PVD harsh touch sensory neuron
      requires the mec-3 Lhx gene. Lastly, we analyze a mutant allele of the ser-2
      tyramine receptor, a target of the ttx-3 Lhx gene in the AIY interneuron class.
      ser-2 mutants display none of the defects previously shown to be associated with
      loss of AIY function.

PMID- 14568552
TI  - Chondrocyte-derived transglutaminase promotes maturation of preosteoblasts in
      periosteal bone.
AB  - During endochondral development, elongation of the bone collar occurs
      coordinately with growth of the underlying cartilaginous growth plate.
      Transglutaminases (TGases) are upregulated in hypertrophic chondrocytes, and
      correlative evidence suggests a relationship between these enzymes and
      mineralization. To examine whether TGases are involved in regulating
      mineralization/osteogenesis during bone development, we devised a coculture
      system in which one cellular component (characterized as preosteoblastic) is
      derived from the nonmineralized region of the bone, and the other cellular
      component is hypertrophic chondrocytes. In these cocultures, mineralization is
      extensive, with the preosteoblasts producing the mineralized matrix, and the
      chondrocytes regulating this process. Secreted regulators are involved, as
      conditioned medium from chondrocytes induces mineralization in preosteoblasts,
      but not vice versa. One factor is TGase. In the cocultures, inhibition of TGase
      reduces mineralization, and addition of the enzyme enhances it. Exogenous TGase
      also induces markers of osteoblastic differentiation (i.e., bone sialoprotein and
      osteocalcin) in the preosteoblasts, suggesting their differentiation into
      osteoblasts. Two possible signaling pathways may be affected by TGase and result
      in increased mineralization (i.e., TGF-beta and protein kinase A pathways).
      Addition of exogenous TGF-beta2 to the cocultures increases mineralization;
      though, when mineralization is induced by TGase, there is no detectible elevation
      of TGF-beta, suggesting that these two factors stimulate osteogenesis by
      different pathways. However, an interrelationship seems to exist between TGase
      and PKA-dependent signaling. When mineralization of the cocultures is stimulated
      through the addition of TGase, a concomitant reduction (50%) in PKA activity
      occurs. Consistent with this observation, addition of an activator of PKA (cyclic
      AMP) to the cultures inhibits matrix mineralization, while known inhibitors of
      PKA (H-89 and a peptide inhibitor) cause an increase in mineralization. Thus, at
      least one mechanism of TGase stimulation probably involves inhibition of the PKA
      mediated signaling.

PMID- 14568551
TI  - Oocyte-dependent activation of mitogen-activated protein kinase (ERK1/2) in
      cumulus cells is required for the maturation of the mouse oocyte-cumulus cell
      complex.
AB  - Luteinizing hormone (LH) induces maturational processes in oocyte-cumulus cell
      complexes (OCC) of preovulatory follicles that include both resumption of meiosis
      in the oocyte and expansion (mucification) of the cumulus oophorus. Both
      processes require activation of mitogen-activated protein kinase (MAPK) in
      granulosa cells. Here, it is reported that inhibition of MAPK activation
      prevented gonadotropin-stimulated resumption of meiosis as well as the rise in
      expression of two genes whose products are necessary for normal cumulus
      expansion, Has2 and Ptgs2. However, inhibition of MAPK did not block gonadotropin
      induced elevation of granulosa cell cAMP, indicating that the activation of MAPK
      required for inducing GVB and cumulus expansion is downstream of cAMP. Moreover,
      activation of MAPK in cumulus cells requires one or more paracrine factors from
      the oocyte to induce GVB and cumulus expansion; MAPK activation alone is not
      sufficient to initiate these maturational processes. This study demonstrates a
      remarkable interaction between the oocyte and cumulus cells that is essential for
      gonadotropin-induced maturational processes in OCC. By enabling gonadotropin
      dependent MAPK activation in granulosa cells, oocytes promote the generation of a
      return signal from these cells that induces the resumption of meiosis. It also
      appears that an oocyte-dependent pathway downstream from oocyte-enabled
      activation of MAPK, and distinct from that promoting the resumption of meiosis,
      governs cumulus expansion.

PMID- 14568553
TI  - Role for laminin-alpha5 chain LG4 module in epithelial branching morphogenesis.
AB  - Laminin-alpha5 chain was localized in all epithelial basement membranes (BMs) of
      mouse submandibular gland (SMG) from the onset of branching morphogenesis and
      became restricted to BMs of epithelial ducts in the adult. To investigate whether
      the laminin-alpha5 chain plays a role in branching morphogenesis, a set of cell
      adhesive peptides from the C-terminal globular domains (LG1-5) was tested for
      their effects in SMG organ cultures. One peptide, LVLFLNHGH (A5G77f), which
      represents a sequence located in the connecting loop between strands E and F of
      LG4, perturbed branching morphogenesis and resulted in irregularities in the
      contours of epithelial structures, with formation of deep clefts. The data
      suggest a role for the laminin-alpha5 LG4 module in the development of the duct
      system, rather than in the bifurcation of epithelial clusters. The epithelial BM
      of A5G77f-peptide-treated explants was continuous, which was in contrast to our
      previous finding of impaired epithelial BM assembly in explants treated with the
      laminin-alpha1 LG4 module peptide, or with a monoclonal antibody against this
      domain. A5G77f also perturbed in vitro development of lung and kidney. These
      results suggest a crucial role for the LG4 module of laminin-alpha5 in epithelial
      morphogenesis that is distinct from that of the laminin-alpha1 LG4.

PMID- 14568554
TI  - Rapid annexin-V labeling in synaptosomes.
AB  - Distal neuronal terminals may be the site of apoptotic events and early synapse
      loss in neurodegenerative disease. To examine apoptosis in synaptic regions, we
      established a cell-free assay using a rat brain crude synaptosomal preparation (P
      2 fraction) as a model system. The apoptosis marker annexin-V was used to measure
      phosphatidylserine (PS) exposure, and to ensure that only intact terminals were
      assayed, synaptosomes were dual labeled with a viability marker (calcein AM).
      Fluorescence was quantified by flow cytometry analysis. Annexin-V labeling
      increased rapidly in synaptosomes, following a 1 min incubation with
      staurosporine. However, increased caspase-3-like activity was not measured until
      30 min with a fluorometric assay. The addition of a peptide inhibitor of caspase
      3-like activity (Ac-DEVD-CHO) during homogenization was not able to block the
      initial increase in annexin labeling, but resulted in a partial blockade of
      annexin labeling after 30 min. These data demonstrate that PS externalization and
      caspase activation occur rapidly in this widely used neurochemical preparation.

PMID- 14568555
TI  - Vigabatrin inhibits pyridoxine-5'-phosphate oxidase, not pyridoxal kinase in the
      hippocampus of seizure prone gerbils.
AB  - To identify the effects of vigabatrin (VGB) on the metabolism of pyridoxal 5'
      phosphate (PLP) in the seizure prone gerbil hippocampus, we conducted a
      chronological and comparative analysis of pyridoxal kinase (PLK) and pyridoxine
      5'-phosphate oxidase (PNP oxidase) expression. In the VGB treated animals, PNP
      oxidase immunoreactivity was reduced, although the distribution and immunodensity
      of PLK were unaltered, as compared with control animals. In a Western blot study,
      the densities of PNP oxidase immunoreactivities in VGB treated animals were found
      to have decreased significantly. However, no differences in PLK immunoreactive
      bands were observed in controls or in VGB treated animals. By enzyme activity
      assay, and in contrast to PLK, the specific activity of PNP oxidase in the VGB
      treated gerbils was significantly reduced. In conclusion, the present data
      presents a piece of in vivo evidence that supports the anti-epileptic effects
      mediated by pyridoxamine-5'-phosphate (PMP) metabolism, and which may be helpful
      in the development of an anti-epileptic drug.

PMID- 14568556
TI  - Modulation of noradrenaline release in the median preoptic area by GABAergic
      inputs from the organum vasculosum of the lamina terminalis in the rat.
AB  - Previous observations have shown that gamma-aminobutyric acid (GABA) receptor
      mechanisms modulate the release of noradrenaline (NA) in the median peptic
      nucleus (MnPO). The present study was carried out to investigate whether neural
      inputs from the organum vasculosum of the lamina terminalis (OVLT) to the MnPO
      are involved in the GABAergic modulation of NA release in the MnPO area using in
      vivo microdialysis techniques. In urethane-anesthetized rats, electrical
      stimulation (5 and 10 microA, 10Hz) of the OVLT region, but not its surrounding
      region, significantly enhanced dialysate NA concentration in the MnPO area. The
      enhancement in the NA level caused by the OVLT region stimulation was
      significantly increased by perfusion with either bicuculline (10 microM), a
      GABA(A) receptor antagonist, or phaclofen (10 microM), a GABA(B) receptor
      antagonist, through a microdialysis probe. The amount of the antagonist-induced
      increase was much greater in the phaclofen-treated group than in the bicuculline
      treated group. These results show that the OVLT region may exert both excitatory
      and inhibitory influences on the release of NA in the MnPO area, and imply that
      the inhibitory influence may be mediated through GABA(B) receptors rather than
      GABA(A) receptors.

PMID- 14568557
TI  - Changes in the expression of calbindin D-28k in the gerbil hippocampus following
      seizure.
AB  - Previous studies have reported that calbindin D-28k (CB), a calcium-binding
      protein, containing neurons in the hippocampus play an important role in
      hippocampal excitability in epilepsy, because CB modulates the free calcium ion
      during seizure. Hence, in the present study, we investigated changes of CB
      expression in the hippocampus and its association in the Mongolian gerbil to
      identify roles of CB in epileptogenesis. CB immunoreactivity in the hippocampus
      was significantly lower in the pre-seizure group of seizure sensitive (SS)
      gerbils as compared with those seen in the seizure resistant (SR) gerbils. The
      distribution of CB immunoreactivity in the hippocampus showed significant
      difference after seizure on-set in SS gerbils. CB immunoreactivity in the
      hippocampal CA1, CA2 areas, and subiculum was lowest at 3h after seizure on-set;
      thereafter, the immunoreactivity became to increase to 12h after seizure on-set.
      Mossy fibers, Schaffer collaterals and dentate granule cells showed the highest
      CB immunoreactivity at 3h after seizure on-set; thereafter, the immunoreactivity
      became to decrease. In the case of the intrinsic and output connections of the
      hippocampus, a rapid decrease of CB serves an inhibitory function, which
      regulates the seizure activity and output signals from the hippocampus.

PMID- 14568558
TI  - Glutathione monoethylester prevents mitochondrial glutathione depletion during
      focal cerebral ischemia.
AB  - Glutathione is a central component in the antioxidant defences of cells. We have
      recently reported an early and selective loss of total (reduced plus oxidised)
      glutathione from mitochondria isolated from rat brain following occlusion of the
      middle cerebral artery. This mitochondrial glutathione depletion showed an
      apparent association with the tissue damage that developed during subsequent
      reperfusion, suggesting that it could be an important determinant of
      susceptibility to cell loss. In the present study, we have investigated whether
      in vivo treatment with glutathione ethyl ester can modulate mitochondrial
      glutathione in the brain and whether this treatment can influence the response to
      focal ischemia. In further support of our previous findings, middle cerebral
      artery occlusion caused a duration-dependent partial loss of mitochondrial
      glutathione. Bilateral injections of glutathione ethyl ester immediately prior to
      induction of unilateral focal ischemia resulted in a substantial increase in
      glutathione in mitochondria from the striatum of both the non-ischemic hemisphere
      (190% of saline-treated controls) and the ischemic hemisphere (240% of controls)
      at 2h after arterial occlusion. Total tissue glutathione was not affected by the
      ester treatment at this time. A smaller increase in mitochondrial glutathione was
      observed at 3h of occlusion in the non-ischemic striatum following ester
      treatment but at this time point glutathione was not significantly altered in
      mitochondria from the ischemic hemisphere. Pre-ischemic treatment with
      glutathione ester did not significantly change the volume of tissue infarction
      assessed at 48 h following ischemia for 2 or 3h. These studies demonstrate that
      glutathione ethyl ester is a highly effective modulator of the mitochondrial
      glutathione pool in the intact brain and provides a useful means for further
      investigating the role of this antioxidant in the development of tissue damage in
      ischemia and other brain disorders.

PMID- 14568559
TI  - alpha-Glycerylphosphorylethanolamine rescues astrocytes from mitochondrial
      impairment and oxidative stress induced by amyloid beta-peptides.
AB  - The present work shows that alpha-glycerylphosphorylethanolamine (alpha-GPE) is
      effective in recovering astrocytes from mitochondrial membrane integrity and
      potential derangement and cellular oxidative stress that occur under amyloid beta
      peptides-induced reactive gliosis.alpha-Glycerylphosphorylethanolamine (alpha
      GPE), a new compound with nootropic properties, known to improve in vivo the
      learning and memory processes, has been tested for its protective properties on
      an in vitro model of degeneration. Rat primary astrocytic cultures treated with
      two amyloid-derived peptides, Abeta((1-40)) and Abeta(3(pE)-42), showed a marked
      reduction of the mitochondrial redox activity and membrane potential, together
      with an increase of oxidative species production. Plasma membrane lipid
      peroxidation (LPO) as well as generation of peroxides is greatly increased under
      Abeta-peptides toxicity. These features, typical of the reactive gliosis that
      accompanies neuronal degeneration, were readily recovered by pretreatment with
      alpha-GPE. alpha-GPE, likely improving the fluidity of cell membrane, has the
      potential to recover astrocytes from the general redox derangement induced by
      different amyloid fragments and possibly to protect from inflammation, gliosis
      and neurodegeneration. This is the first evidence of an antioxidant effect of the
      ethanolamine derivative on a rat model of chronic gliosis.

PMID- 14568560
TI  - Inhibition of hippocampal LTP by ginkgolide B is mediated by its blocking action
      on PAF rather than glycine receptors.
AB  - Platelet-activating factor (PAF), a biologically active lipid (1-O-alkyl-2-acetyl
      sn-glycero-3-phosphoholine), is identified in different regions of brain,
      including hippocampus. Specific PAF-activated receptors (PAFRs) are expressed in
      corresponding brain areas. PAF has been proposed to be a retrograde messenger of
      long-term potentiation (LTP): the antagonist of PAFRs, ginkgolide B (or BN52021)
      prevents induction of LTP. Recently it has been found that ginkgolide B is also
      an efficient blocker of the glycine receptor (GlyR) operated chloride channels
      (IC(50)=270+/-10 nM in hippocampal pyramidal neurons). The question is as
      follows: is the alteration of LTP by BN52021 due to the PAF antagonism or to the
      inhibition of glycine-gated chloride channels? We have studied the effects of
      ginkgolides B and J on LTP induced in the CA1 area of rat hippocampus. Ginkgolide
      J which is the weakest blocker of PAFR (IC(50)=54 microM, as compared to
      IC(50)=2.5 microM for ginkgolide B) inhibits GlyR-operated channels with
      IC(50)=2.0 microM. This assures a convenient concentration window which allows to
      inhibit GlyR-operated channels without affecting PAFRs. An amount of 5 microM of
      ginkgolide J did not prevent the induction of LTP, while ginkgolide B (5 microM)
      completely inhibited this phenomenon. The effect of ginkgolide B on LTP did not
      alter considerably if GlyRs were blocked by strychnine (2 microM). Strychnine
      itself had no significant effect on the induction of LTP. Both ginkgolides and
      strychnine significantly facilitated short-term potentiation (STP). Our data
      support a hypothesis according to which ginkgolides affect LTP by inhibiting
      PAFRs.

PMID- 14568561
TI  - Postpartum changes in the GABAergic system in the bed nucleus of the accessory
      olfactory tract.
AB  - The bed nucleus of the accessory olfactory tract (BAOT) is a sexually dimorphic
      structure which controls the inhibition/disinhibition of the medial preoptic area
      in the expression of maternal behavior. Therefore, in the present study we
      investigated sex differences and the modulation of gamma-aminobutiric-acid (GABA)
      in the BAOT during the first two postpartum days. Four groups of Wistar rats:
      control males, control females, 0 h postpartum females and 48 h postpartum
      females, were used in this experiment. Sex differences in glutamate decarboxylase
      (GAD) and GABA(A) alpha-chain receptor densities were apparent in the BAOT. The
      hormonal and behavioral postpartum state affects GABAergic activity in the
      females' BAOT in two ways: firstly, pregnancy and the first two postpartum days
      induce an increase in GABA(A)-receptor and GAD densities; secondly, the intensity
      of these activities are greater in the left hemisphere than in the right. These
      changes might be related to the BAOT's function of inhibiting/disinhibiting
      maternal behavior.

PMID- 14568562
TI  - Estrogen receptor-alpha and Sp1 interact in the induction of the low density
      lipoprotein-receptor.
AB  - Both estrogen and selective estrogen receptor modulators (SERMs) such as
      tamoxifen and raloxifene have been demonstrated to lower plasma low density
      lipoprotein (LDL)-cholesterol concentrations by stimulation of LDL receptor gene
      expression. To determine the molecular mechanisms of estradiol- and tamoxifen
      induced LDL receptor expression, we performed transient transfection experiments
      with luciferase reporter gene-constructs under transcriptional control of the
      human LDL receptor promoter. We demonstrate, that estradiol and tamoxifen
      stimulate LDL receptor gene expression in human HepG2 hepatoma cells only when
      estrogen receptor (ER)-alpha but not when ER-beta is cotransfected. Deletion
      mutants and point mutations of the LDL receptor promoter reveal that estradiol-
      and tamoxifen-stimulated expression of this gene depends on an intact repeat 3 in
      the LDL receptor promoter, a cis-element previously shown to interact with Sp1.
      Gel mobility analyses demonstrated estradiol- and tamoxifen-stimulated binding of
      nuclear proteins to repeat 3 (bp -56 to bp -36) of the LDL receptor promoter.
      These data provide an alternative mechanism of LDL receptor gene expression by
      non-classical estradiol- and tamoxifen-stimulated induction through an ER
      alpha/Sp1 complex.

PMID- 14568563
TI  - Molecular cloning and expression of guinea pig cytochrome P450c21 cDNA (steroid
      21-hydroxylase) isolated from the adrenals.
AB  - In mammals, the P450c21 enzyme mediates 21-hydroxylase activity by transforming
      progesterone and 17-hydroxyprogesterone into deoxycorticosterone (DOC) and 11
      deoxycortisol (11-DOC), respectively. Previous studies have shown that among the
      adrenal steroid hydroxylase enzymes involved in C19 steroid and glucocorticoid
      syntheses, P450c21 plays an important role, because it is localized at the key
      branch between glucocorticoids and C19 steroid production. Its implication in
      congenital adrenal hyperplasia is also of great clinical interest. In this study,
      in addition to describing the isolation of the P450c21 cDNA from guinea pig (GP)
      adrenal and comparing it to those from other species, we report on its tissue
      distribution and on the activity of the recombinant protein towards progesterone
      and 17-hydroxyprogesterone. The guinea pig P450c21 includes the full-length
      coding region (1464 nucleotide) that is translated to a protein of 488 amino
      acids. The clone shares highly conserved regions with other species. The guinea
      pig P450c21 cDNA hybridized with a major transcript of 2.1kb and with two minor
      related transcripts of 1.8 and 1.5 kb and was found to be adrenal-specific among
      the various tissues analyzed. Characterization of the enzymatic activity by
      transient transfection of the guinea pig P450c21 cDNA in human embryonic kidney
      293 cells indicated a net preference for the 21-hydroxylation of 17
      hydroxyprogesterone in comparison to the progesterone substrate. Assays showed a
      maximum conversion rate of 12.5% for the conversion of progesterone into
      deoxycorticosterone (mineralocorticoid pathway), whereas the guinea pig P450c21
      demonstrated a higher activity with 17alpha-hydroxyprogesterone, with 55% of 11
      deoxycortisol formation (glucocorticoid pathway) after 48 h. Adrenocorticotropin
      and an analogue of the second messenger cyclic adenosine monophosphate
      specifically increased the abundance of P450c21 mRNA levels in guinea pig adrenal
      cells.

PMID- 14568564
TI  - Binding of the pheromonal steroid, 5alpha-androst-16-en-3-one, to membrane
      enriched fractions of boar and rat olfactory epithelium; preliminary evidence for
      binding protein being a glycoprotein.
AB  - A high degree of binding of 5alpha-[3H]-androstenone was recorded in membrane
      enriched fractions of porcine olfactory tissue. The specific (i.e. high affinity,
      low capacity) binding had a mean Ka approximately 2x10(8)M(-1). A Hill plot of
      the data showed a Hill coefficient of approximately 2, possibly suggesting co
      operativity of binding, with binding constants increasing from 8x10(7) to
      1.6x10(9)M(-1) with increasing substrate concentration. The level of specific
      binding of 5alpha-[3H]-androstenone was nearly 10-fold higher than in
      corresponding respiratory tissue preparations and was markedly reduced in the
      presence of excess (approximately 1 microM) unlabelled 5alpha-androstenone.
      Corresponding fractions derived from rat olfactory tissue showed only 25% of the
      binding recorded for the pig. After incubation of 5alpha-[3H]-androstenone with
      solubilised olfactory cilial tissue (porcine), gel filtration and chromatography
      on a typical "glycoprotein" column (Concanavalin A-Sepharose B) were performed.
      Specific binding was recorded only in fractions corresponding to glycoproteins
      with Mr of approximately 70-90 kDa. In a third series of experiments, fractions
      containing high concentrations of cilia, some still attached to the dendritic
      endings (as shown by electron microscopy) were obtained by a novel method
      involving stripping them off the nasal epithelium. The basal adenylate cyclase
      (AC) activity was very significantly (P<0.01) higher in olfactory, compared with
      respiratory, cilia; storage at -70 degrees C for 3 weeks greatly reduced AC
      activity. When fresh male and female porcine olfactory cilia preparations were
      incubated with 5alpha-androstenone plus GTP, AC activity was increased fourfold
      (P<0.01). However, responses of porcine respiratory cilia were not significant
      statistically, neither were changes in basal levels of AC activities in rat
      olfactory cilia.

PMID- 14568565
TI  - Full-length estrogen receptor alpha and its ligand-binding domain adopt different
      conformations upon binding ligand.
AB  - The binding of ligand to a nuclear receptor causes conformational changes that
      can result in coactivator or corepressor recruitment and subsequent regulation of
      transcription. Several peptides have previously been identified that bind to the
      liganded estrogen receptor (ER). One interacting peptide, pepalphaII, was used in
      the present studies to assess the ability of ligands to induce spatial changes
      within both the full-length human estrogen receptor alpha (ER-alpha) and a
      truncated receptor containing the ligand-binding domain (LBD). pepalphaII
      interacted weakly with the full-length estrogen receptor alpha in the presence of
      both agonists and antagonists. In contrast, the interaction of pepalphaII with
      the truncated receptor containing the ligand-binding domain was strongly induced
      by antagonists and only weakly induced by agonists. Thus, the same ligand can
      induce different spatial configurations of the full-length and ligand-binding
      domain of estrogen receptor alpha as measured by pepalphaII affinity. Crystal
      structures of nuclear hormone receptors solved to date have used ligand-binding
      domains and therefore may not accurately predict surface interaction domains
      present in the liganded full-length receptor. Furthermore, the ability of a
      ligand to induce a strong interaction of pepalphaII with the estrogen receptor
      alpha ligand-binding domain predicts that the ligand will have greater antagonist
      activity on the full-length receptor.

PMID- 14568566
TI  - Insulin-like growth factor I (IGF-I) regulates endocrine activity of the
      embryonic testis in the mouse.
AB  - Insulin-like growth factor I (IGF-I) is important for gonadal and reproductive
      functions in mammals, although the physiological role of this growth factor
      during gonadal development in rodents remains largely unknown. Here, we examined
      the steady-state levels of IGF-I mRNA by the reverse transcriptase polymerase
      chain reaction (RT-PCR). IGF-I protein expression was also detected by Western
      blot. The effect of IGF-I as promoter of 17alpha-hydroxylase/C17-20 lyase and
      17beta-hydroxysteroid dehydrogenase enzyme activity in vitro was evaluated by
      radioimmunoassay. Onset of IGF-I gene expression was on day E10 (urogenital ridge
      stage). IGF-I mRNA expression was markedly reduced on days E12 and E13
      (testicular differentiation stage). IGF-I transcripts increased on day E14 and
      their transcription levels were maintained throughout the stages analyzed.
      Several IGF-I protein bands of 31-100 kDa were observed. Culture experiments
      demonstrated that 17alpha-hydroxyprogesterone and testosterone (T) secretion
      levels increased in the presence of IGF-I on days E11-E17. Additive effects of
      IGF-I plus (Bu)2cAMP were also seen during testicular development. It is proposed
      that IGF-I regulates the expression of key steroidogenic enzymes important for
      endocrine activity of the testis during prenatal development leading to
      establishment of the male phenotype and fertility.

PMID- 14568567
TI  - Formation of estrone and estradiol from estrone sulfate by normal breast
      parenchymal tissue.
AB  - The study was designed to determine the process and limitations by which estrone
      sulfate may be a precursor of estradiol in the parenchymal cells of the normal
      breast. The concentration of estrone sulfate in breast nipple aspirate fluid was
      1000-fold greater than that of estradiol. Concentrations of 3H-estrone sulfate in
      parenchymal cells were only 0.20-0.33 times that of the 1.0 nM concentration in
      the medium, while 3H-estrone achieved concentrations up to 24 times that in the
      medium at 37 degrees C. Nevertheless, estrone sulfate added to the medium was
      linearly converted within a 1000-fold concentration range to estrone in intact
      cells with a mean half-time of conversion of 628 min per 10(6) cells. Homogenized
      cells had a half-time of 246 min per 10(6) cells. Thus, the time for entry of
      estrone sulfate into cells reduced the rate by approximately 55%. In split
      samples, the Vmax values (+/- S.D.) for intact and homogenized cells were 12.6 +/
      1.4 and 18.3 nmol/h mg DNA, respectively (P<0.03). The corresponding Km values
      for intact and homogenized cells were 6.0 +/- 1.1 and 4.7 +/- 1.0 microM.
      Conversion of estrone sulfate to estradiol was more efficient in intact cells
      than in homogenates with mean half-times of 2173 and 7485 min per 10(6) cells,
      respectively. Conversion of estrone to estrone sulfate did not occur in these
      cells despite sulfonation of estrone by MCF-7 breast cancer cells under identical
      conditions. It is concluded that estrone sulfate can serve as a precursor for
      estradiol in normal breast tissue. Conversion of estrone to estradiol is a
      limiting step in the process.

PMID- 14568568
TI  - Correlation between butyrate-induced histone hyperacetylation turn-over and c-myc
      expression.
AB  - Transcriptionally active chromatin has an high level of histone acetylation, a
      post-transcriptional modification known to alter nucleosomal conformation
      increasing the accessibility of transcription factors to DNA. Recent studies have
      led new interest in histone acetylase and deacetylase because of their role as
      transcription factors. Sodium butyrate, a known reversible inhibitor of histone
      deacetylase, modulates a large number of genes. This report is focused on the
      modulation of the c-myc oncogene expression by butyrate. In HeLa cells, treated
      with butyrate and then exposed to butyrate-free medium, we established a
      correlation between the reactivation kinetic of c-myc expression and the increase
      in level of histone H4 acetylation. Both parameters, in cells exposed to butyrate
      free medium, after showing a rebound effect, return to the control level. This
      trend was confirmed by quantitative analysis of the level of histone acetylation
      and of c-myc expression in the three distinct class of nucleosomal fragments with
      different transcriptional activity. In this chase process, we also detected a
      concomitant enrichment in c-myc sequences in the "active" chromatin fractions and
      decreased presence in the inactive nucleosomal fragment. Therefore we here
      demonstrate an excellent correlation between histone hyperacetylation and
      reactivation of a specific gene (c-myc).

PMID- 14568569
TI  - Dexamethasone decreases phospholipase C beta1 isozyme expression in human
      vascular smooth muscle cells.
AB  - The molecular characterization of the human PLC beta1 gene was just reported by
      Peruzzi et al. [Biochim. Biophys. Acta 1582 (2002) 46]. This prompted us to
      investigate the effects of dexamethasone on PLC beta1 expression in two types of
      human vascular smooth muscle cells--coronary artery smooth muscle cells (hCASMC)
      and aortic smooth muscle cells (hAoSMC), since glucocorticoids are known to
      affect the signaling pathways of Gprotein coupled receptors. Semi-quantitative RT
      PCR was used to analyze mRNA expression and Western-blot for protein expression.
      Dexamethasone treatment in the two types of cells studied decreased (mRNA and
      protein) PLC beta1 isozyme expression. A rapid (2 h) fall in mRNA occurred in
      hCASMC after treatment, and hCASMC were more sensitive to dexamethasone (1 nM
      versus 100 nM) than hAoSMC. The major reduction (80%) was observed after 48 h of
      exposure in both VSMC. Treatment with mifeprisone, an antagonist of
      glucocorticoid receptors, blunted the dexamethasone effect on PLC beta1 mRNA and
      showed that this effect was mediated by glucocorticoids receptors.

PMID- 14568570
TI  - Silymarin is a selective estrogen receptor beta (ERbeta) agonist and has
      estrogenic effects in the metaphysis of the femur but no or antiestrogenic
      effects in the uterus of ovariectomized (ovx) rats.
AB  - Silymarin is a widely used standardized mixture of flavonolignans and its major
      component Silybinin binds to cytosolic estrogen receptors. Here, we demonstrate
      that this binding is exclusive to the estrogen receptor beta (ERbeta). Treatment
      of ovariectomized (ovx) rats with silymarin or estradiol (E2) may allow
      differentiation of biological effects mediated by the ERalpha or ERbeta. E2
      inhibited serum LH, cholesterol, LDL and HDL concentrations in the blood and
      increased gene expression of IGF1, HbEGF and C3 in the uterus, while silymarin
      was totally ineffective or antagonistic in altering these parameters. Both, E2
      and silymarin inhibited expression of uterine ERbeta gene. Hence, in the
      pituitary, liver (where the lipoproteins are synthesized) and uterus E2 acts
      primarily via the ERalpha. Exclusive estrogenic effects of silymarin were
      observed in the metaphysis of the femur (MF), on osteoblast parameters (gene
      expression of IGF1, TGFbeta1, osteoprotegerin, collagen-1alpha1, osteocalcin
      (OC)) and on the osteoclast activity marker tartrate resistant acid phosphatase
      (TRAP) gene expression of adult ovx rats. Our RT-PCR method detects ERbeta gene
      expression in all organs including developing bones but not in the MF of adult
      ovx rats. We conclude therefore, that the effects of silymarin in this part of
      the bone cannot be exerted via the ERalpha because it does not bind to this
      receptor subtype. Despite the failure to detect ERbeta mRNA in the MF of our
      animals the possibility exists that ERbeta protein is present and may mediate the
      effects of silymarin. Another possibility may be that the effect of silymarin and
      therefore possibly also of E2 in the MF may be mediated via other possibly not
      yet identified receptors or via an ERbeta splice variant which is not detected by
      our PCR-method.

PMID- 14568571
TI  - The effects of 2-methoxy oestrogens and their sulphamoylated derivatives in
      conjunction with TNF-alpha on endothelial and fibroblast cell growth, morphology
      and apoptosis.
AB  - 2-methoxyoestradiol (2-MeOE2) is a potent anti-angiogenic agent. Its 3- and 17
      sulphamoylated derivatives have been demonstrated to induce G2-M cell cycle
      arrest and apoptosis in breast cancer cells in vitro as well as tumour regression
      in rats in vivo with greater potency than the parent oestrogen. To determine
      whether the anti-cancer properties of these derivatives can be synergistically
      enhanced with low-dose TNF-alpha co-treatment, we investigated the effects of
      these treatments in adult human fibroblasts and human umbilical vein endothelial
      cells (HUVECs). Treatment of fibroblasts with 0.1 microM 2-methoxyoestradiol-3,17
      bis sulphamate (2-MeOE2bisMATE) but not 2-MeOE2 caused a reversible morphology
      change and induced G2-M arrest (from 12 to 33%) but not subsequent apoptosis. In
      contrast, treatment of HUVECs did not induce morphology change or G2-M arrest.
      Using a nucleosomal ELISA assay, we showed that TNF-alpha (20 ng/ml) combination
      treatment synergistically increases 0.1 microM 2-MeOE2bisMATE-induced but not 0.1
      microM 2-MeOE2-induced apoptosis in HUVECs. These results suggest that TNF-alpha
      co-treatment may be a beneficial method of increasing the potency of 2
      substituted oestrogens as anti-angiogenic agents through synergistic induction of
      apoptosis in endothelial cells while maintaining low cytotoxicity to fibroblasts.

PMID- 14568572
TI  - Comparative studies on the regulation of insulin-like growth factor-binding
      protein-1 (IGFBP-1) and sex hormone-binding globulin (SHBG) production by insulin
      and insulin-like growth factors in human hepatoma cells.
AB  - Production of insulin-like growth factor-binding protein-1 (IGFBP-1) by the liver
      is efficiently inhibited by insulin both in vivo and in vitro. Consequently,
      serum IGFBP-1 concentration reflects insulin bioactivity in portal vein. Sex
      hormone-binding globulin (SHBG) is another insulin-regulated liver-derived
      protein that has appeared promising in detecting individuals with portal
      hyperinsulinemia. We compared the regulation of IGFBP-1 and SHBG production by
      insulin and insulin-like growth factors (IGF-I and IGF-II) in human hepatoma cell
      cultures. Insulin equipotently inhibited IGFBP-1 and SHBG production, with
      maximal decrease in culture medium concentrations being about 35% for both
      proteins during 48 h of culture in serum-free medium. IGF-I and IGF-II also
      inhibited the IGFBP-1 and SHBG levels. We conclude that IGFBP-1 and SHBG are
      equally sensitive to ambient insulin concentrations in human hepatoma cell
      cultures, and the production of both proteins is also attenuated by the IGFs.

PMID- 14568573
TI  - The effect of glucocorticoids on the myosin heavy chain isoforms' turnover in
      skeletal muscle.
AB  - The purpose of this study was to find the effect of dexamethasone on the myosin
      heavy chain (MyHC) isoforms' composition in different skeletal muscles and
      glycolytic (G) fibres in relation with their synthesis rate and degradation of
      MyHC isoforms by alkaline proteinases. Eighteen-week-old male rats of the Wistar
      strain were treated with dexamethasone (100 microg/100 g bwt) during 10 days. The
      forelimb strength decreased from 9.52 to 6.19 N (P<0.001) and hindlimb strength
      from 15.54 to 8.55 N (P<0.001). Daily motor activity decreased (total activity
      from 933 to 559 and ambulatory activity from 482 to 226 movements/h, P<0.001).
      The degradation rate of muscle contractile proteins increased from 2.0 to 5.9%
      per day (P<0.001), as well as the myosin heavy chain IIB isoform degradation with
      alkaline proteinase in fast-twitch (F-T) muscles (12 +/- 0.9%; P<0.05) and
      glycolytic muscle fibres (15 +/- 1.1%; P<0.001). The synthesis rate of MyHC type
      II isoforms decreased in Pla muscles (P<0.05) and MyHC IIA (P<0.05) and IIB in
      EDL muscle and G fibres (P<0.001). The relative content of MyHC IIB isoform
      decreased in F-T muscles (P<0.001) and in G fibres (P<0.01), and the relative
      content of IIA and IID isoforms increased simultaneously. Dexamethasone decreased
      the MyHC IIB isoform synthesis rate and increased the sensibility of MyHC IIB
      isoform to alkaline proteinase, which in its turn led to the decrease of MyHC IIB
      isoform relative content in F-T muscles with low oxidative potential and G muscle
      fibres.

PMID- 14568574
TI  - Sex steroid hormone metabolism takes place in human ocular cells.
AB  - Steroids are potentially important mediators in the pathophysiology of ocular
      diseases. In this study, we report on the gene expression in the human eye of a
      group of enzymes, the 17beta-hydroxysteroid dehydrogenases (17HSDs), involved in
      the biosynthesis and inactivation of sex steroid hormones. In the eye, the
      ciliary epithelium, a neuroendocrine secretory epithelium, co-expresses the
      highest levels of 17HSD2 and 5 mRNAs, and in lesser level 17HSD7 mRNA. The
      regulation of gene expression of these enzymes was investigated in vitro in cell
      lines, ODM-C4 and chronic open glaucoma (GCE), used as cell models of the human
      ciliary epithelium. The estrogen, 17beta-estradiol (10(-7) M) and androgen
      agonist, R1881 (10(-8) M) elicited in ODM-C4 and GCE cells over a 24 h time
      course a robust up-regulation of 17HSD7 mRNA expression. 17HSD2 was up-regulated
      by estradiol in ODM-C4 cells, but not in GCE cells. Under steady-state
      conditions, ODM-C4 cells exhibited a predominant 17HSD2 oxidative enzymatic
      activity. In contrast, 17HSD2 activity was low or absent in GCE cells. Our
      collective data suggest that cultured human ciliary epithelial cells are able to
      metabolize estrogen, androgen and progesterone, and that 17HSD2 and 7 in these
      cells are sex steroid hormone-responsive genes and 17HSD7 is responsible to keep
      on intra/paracrine estrogenic milieu.

PMID- 14568575
TI  - Ultrastructure and function of long and short sperm in Cicadidae (Hemiptera).
AB  - The cicada, Graptopsaltria nigrofuscata, produces two distinct sizes of sperm, as
      determined by either nuclear volume of early spermatids or nuclear length of
      mature sperm. Between both sperm, there is no difference in location of the
      acrosome and flagellum during spermiogenesis. The acrosome is covered by an
      anteacrosomal bleb, which is inserted in a common mass, spermatodesm, derived
      from cyst cells. Both kinds of sperm linked to the spermatodesm form sperm
      bundles, respectively. During copulation, the sperm bundles are transported from
      the vesicula seminalis of the male to the bursa copulatrix of the female.
      Morphometric analyses of the nuclear length revealed that the two kinds of sperm
      reach the bursa copulatrix in the same condition as that found in the vesicula
      seminalis. Once transferred inside the latter, the sperm bundles disintegrated to
      individual sperm within a few hours, and the tail components, such as the axoneme
      and mitochondrial derivatives, become separated from each other over time. The
      tail completely splits from the sperm nucleus 24 h after copulation. Fertile
      sperm accumulate in the spermatheca, the final storage organ, where only long
      sperm survived for any length of time. Fertilized eggs examined by vital staining
      contain only sperm with long nuclei.

PMID- 14568576
TI  - Age-related variation in mean sperm length, in the rove beetle Aleochara
      bilineata.
AB  - The rove beetle, Aleochara bilineata, is characterised as having monomorphic long
      sperm (spermatophoral mean approx. +/-2.5%), whilst simultaneously having a large
      variation in mean sperm length across a mixed age population. Spermatophoral
      means of between 627 and 996 mum were measured in this investigation. The
      hypothesis that sperm length increases as a function of male age is tested. In
      order to examine this hypothesis in a 'good genes' context, three a priori
      subhypotheses were tested: (1) spermatophoral mean sperm length increases as a
      function of male age and not as a function of the sequential order of the
      spermatophore from which sperm were taken, (2) the rate of this increase is
      dependent upon nutritional intake, and (3) sperm length is not determined by
      adult body size. The first prediction is supported in its entirety by the data,
      whereas the second is not supported at all and the third subhypothesis is
      supported only in older males. These findings are interesting in the field of
      postcopulatory sexual selection, as this is the first time that such an increase
      in mean sperm length has been recorded.

PMID- 14568577
TI  - Detecting freeze injury and seasonal cold-hardening of cells and tissues in the
      gall fly larvae, Eurosta solidaginis (Diptera: Tephritidae) using fluorescent
      vital dyes.
AB  - This study identified a hierarchy in levels of cold tolerance for diverse tissues
      from larvae of Eurosta solidaginis. Following freezing at -80 degrees C, larval
      survival and the viability of specific tissues were assessed using membrane
      permeant DNA stain (SYBY-14) and propidium iodide. Integumentary muscle,
      hemocytes, tracheae, and the crystal-containing portion of the Malpighian tubules
      were most susceptible to freezing injury. A second group consisting of fat body,
      salivary glands, and the proximal region of the Malpighian tubules were
      intermediate in their susceptibility, while the foregut, midgut, and hindgut were
      the most resistant to freezing injury. Seasonal increases in larval cold
      tolerance were closely matched by changes in the cold tolerance of individual
      tissues. Compared to larvae collected in September, the survival rates for each
      of the six tissues tested from October-collected larvae increased by 20-30%. The
      survival rate in all tissues was notably higher than that of whole animals,
      indicating that larval death could not be explained by the mortality in any of
      the tissues we tested. This method will be useful for assessing the nature of
      chilling/freezing injury, the role cryoprotectants, and cellular changes
      promoting cold tolerance.

PMID- 14568578
TI  - 1,5-Disubstituted imidazoles inhibit juvenile hormone biosynthesis by the corpora
      allata of the mosquito Aedes aegypti.
AB  - We investigated the effect of fifteen 1,5-disubstituted imidazoles (1,5-dis) on
      juvenile hormone III (JH III) and methyl farnesoate (MF) biosynthesis by the
      corpora allata (CA) of the mosquito Aedes aegypti in vitro. Four compounds (TH
      35, TH-83, TH-62 and TH-28) significantly decreased JH biosynthesis in the CA
      dissected from 3-day old sugar-fed females. The decrease of JH synthesis was not
      always associated with increased MF. TH-30 and TH-83 increased MF levels, while
      TH-85 and TH-61 significantly decreased MF levels. Five compounds (TH-26, TH-60,
      TH-83, TH-35 and TH-30) significantly inhibited JH biosynthesis in the CA
      dissected from females 15 h after a blood meal. Four 1,5-dis (TH-30, TH-26, TH-28
      and TH-66) caused MF increases in CA from blood-fed females. 1,5-Disubstituted
      imidazoles had higher inhibitory activity on JH synthesis when substituted at
      position 5 by a 3-benzyloxyphenyl group and at position 1 by a benzyl group (such
      as TH-35). Inhibition of JH and MF biosynthesis by TH-35 was age-dependent and
      influenced by nutritional status; inhibition differed when evaluated in the CA
      dissected from sugar-fed females at different days after emergence and in the CA
      dissected from females at different hours after a blood meal. Inhibition was
      always higher when the CA was more active. The addition of TH-35 significantly
      reduced the stimulatory effect of Aedes-allatotropin and farnesoic acid on JH
      synthesis. This is the first report of an inhibitory effect of 1,5-disubstituted
      imidazoles on JH synthesis in Diptera.

PMID- 14568579
TI  - Isolation of a Drosophila melanogaster desiccation resistant mutant.
AB  - Mutagenesis provides a powerful way of isolating genetic and physiological
      processes underlying complex traits, but this approach has rarely been applied to
      investigating water balance in insects. Here, we describe the isolation of a
      desiccation-resistant mutant of Drosophila melanogaster. Mutagenesis of a
      desiccation sensitive line resulted in the isolation of a mutant with two-fold
      higher resistance. The mutant was partially dominant and mapped to the second
      chromosome. Mutant flies showed lower rates of water loss, and had a higher water
      content, but showed no change in body mass, glycogen content, hemolymph volume or
      water content tolerated at death from desiccation. These physiological
      differences are contrasted to changes in lines of D. melanogaster mass selected
      for altered stress resistance. Isolation of this mutant provides an opportunity
      to identify a gene involved in water balance in insects.

PMID- 14568580
TI  - Juvenile hormone synthesis, metabolism, and resulting haemolymph titre in
      Heliothis virescens larvae parasitized by Toxoneuron nigriceps.
AB  - Last instar larvae of the tobacco budworm, Heliothis virescens F., fail to pupate
      and have little 20-hydroxyecdysone when parasitized by Toxoneuron nigriceps
      (Viereck). In this paper, we extend these observations to juvenile hormone (JH)
      to determine if parasitism by this wasp affects other endocrine systems. To this
      end, we compared the production of JH by corpora cardiaca-corpora allata
      complexes (CC-CA), the metabolism of JH by haemolymph enzymes, and the haemolymph
      titre of JH in parasitized and non-parasitized control larvae of H. virescens
      during the last larval instar. CC-CA from parasitized and control larvae had
      similar peaks of JH synthesis on day 1 of the fifth instar, with JH II accounting
      for more than 90% of total JH in both groups. On subsequent days, JH synthesis
      dropped to undetectable levels more quickly in non-parasitized controls than in
      parasitized larvae. JH metabolism by haemolymph of parasitized and control
      animals increased from low levels on day 1 of the fifth instar to high levels on
      days 2 and 3 of the instar. JH metabolism was significantly higher in control
      larvae than in parasitized larvae. After day 3, JH metabolism decreased in both
      groups, but was significantly higher in parasitized larvae. The major metabolite
      of JH in both groups was JH acid, though traces of JH diol and JH acid diol were
      also detected. The haemolymph titre of JH in both groups peaked on day 1 of the
      fifth instar and, similar to the synthesis of JH by CC-CA, decreased more rapidly
      in control larvae. As a result, non-parasitized animals had significantly lower
      JH titres on day 2. The higher JH titres observed in parasitized larvae during
      the early fifth instar may contribute to their developmental arrest. The possible
      role of these JH alterations in the host developmental and metabolic redirection
      is discussed and a more comprehensive physiological model accounting for host
      parasitoid interactions is proposed.

PMID- 14568581
TI  - Feeding responses of adult butterflies, Nymphalis xanthomelas, Kaniska canace and
      Vanessa indica, to components in tree sap and rotting fruits: synergistic effects
      of ethanol and acetic acid on sugar responsiveness.
AB  - Exuded tree sap and rotting fruits are important feeding sources for adults of
      many butterfly species. However, the chemical composition of such rotting foods
      and the effects of these constituents on butterfly feeding behaviour have rarely
      been investigated. Chemical analyses revealed that these food sources contain
      several major components, including fructose, glucose, ethanol and acetic acid.
      Moreover, 15 amino acids were identified from the exuded tree sap. The gustatory
      responsiveness to these components was examined in the proboscis of nymphalid
      adults of three species (Nymphalis xanthomelas, Kaniska canace and Vanessa
      indica). The first two species primarily feed on sap and rotting fruits, while V.
      indica frequently visits flowers. Fructose elicited larger feeding responses from
      these saprophagous butterflies than glucose, which had a feeding-stimulatory
      effect only on N. xanthomelas at a concentration equivalent to that of the food.
      Ethanol, acetic acid and the five major amino acids identified in tree sap did
      not elicit feeding responses by themselves. However, ethanol and/or acetic acid,
      when mixed with these sugars at equivalent concentrations, evoked feeding and
      enhanced probing responses in K. canace and V. indica. These results suggest that
      ethanol and acetic acid, together with sugars at low concentrations,
      synergistically stimulate butterfly feeding behaviour.

PMID- 14568582
TI  - Stress-induced thermotolerance of ventilatory motor pattern generation in the
      locust, Locusta migratoria.
AB  - Ventilation is a crucial motor activity that provides organisms with an adequate
      circulation of respiratory gases. For animals that exist in harsh environments,
      an important goal is to protect ventilation under extreme conditions. Heat shock,
      anoxia, and cold shock are environmental stresses that have previously been shown
      to trigger protective responses. We used the locust to examine stress-induced
      thermotolerance by monitoring the ability of the central nervous system to
      generate ventilatory motor patterns during a subsequent heat exposure.
      Preparations from pre-stressed animals had an increased incidence of motor
      pattern recovery following heat-induced failure, however, prior stress did not
      alter the characteristics of the ventilatory motor pattern. During constant heat
      exposure at sub-lethal temperatures, we observed a protective effect of heat
      shock pre-treatment. Serotonin application had similar effects on motor patterns
      when compared to prior heat shock. These studies are consistent with previous
      studies that indicate prior exposure to extreme temperatures and hypoxia can
      protect neural operation against high temperature stress. They further suggest
      that the protective mechanism is a time-dependent process best revealed during
      prolonged exposure to extreme temperatures and is mediated by a neuromodulator
      such as serotonin.

PMID- 14568583
TI  - Diurnal variation in supercooling points of three species of Collembola from Cape
      Hallett, Antarctica.
AB  - Daily changes in microclimate temperature and supercooling point (SCP) of
      Collembola were measured during summer at Cape Hallett, North Victoria Land,
      Antarctica. Isotoma klovstadi and Cryptopygus cisantarcticus (Isotomidae) showed
      bimodal SCP distributions, predominantly in the high group during the day and in
      the low group during the night. There were no concurrent diurnal changes in water
      content or haemolymph osmolality. By contrast, Friesea grisea (Neanuridae) had a
      unimodal distribution of SCPs that was invariant between daytime and nighttime.
      Isotoma klovstadi collected foraging on moss had uniformly high SCPs, which
      shifted towards the low group when the animals were starved for 2-8 h. When I.
      klovstadi was acclimated for five days with lichen or algae, SCPs were higher
      than if they were supplied with moss, while those that were starved (with free
      water or 100% relative humidity) displayed a trimodal SCP distribution. A variety
      of pre-treatments, including cold, heat, desiccation and slow cooling were
      ineffective at inducing SCP shifts in C. cisantarcticus or I. klovstadi. It is
      postulated that behavioural avoidance of low temperatures by vertical migration
      may be key in I. klovstadi's short-term survival of nighttime temperatures. These
      data suggest that the full range of thermal responses of Antarctic Collembola is
      yet to be elucidated.

PMID- 14568584
TI  - Development and morphology of teratocytes in Encarsia berlesei and Encarsia
      citrina: first record for Chalcidoidea.
AB  - In several species of hymenopteran parasitoids of the superfamilies of
      Ichneumonoidea and Platygastroidea, the membrane enveloping the parasitoid embryo
      dissociates at hatching into a number of cells, called teratocytes, which
      autonomously develop in the host haemolymph. In this work we report for Encarsia
      berlesei and Encarsia citrina (Hymenoptera: Chalcidoidea), the dissociation of
      the extraembryonic membrane into cells whose morphological and embryological
      features correspond to those of teratocytes. In E. berlesei the membrane
      dissociated at hatching into 4-9 larger cells (100 microm diameter) and about 10
      smaller cells (60 microm), which scarcely doubled their size during maturation.
      In E. citrina the membrane dissociated into five large cells (250 microm) which
      did not grow appreciably. Ultrastructural investigation of the dissociated cells
      in E. berlesei revealed that their surface was covered by microvilli, whose
      density and length increased from the egg stage to the 12 h following hatching.
      During the same period, rough endoplasmic reticulum evolved from a parallel
      profile to that of the cisternal type, while abundant vesicles represented the
      dominant cytological feature. The ploidy level of these cells ranged between 8c
      and 140c at hatching, but increased to 40c-350c at maturation. These findings
      provide the first clear evidences for the presence of teratocytes in the
      superfamily Chalcidoidea.

PMID- 14568587
TI  - [Mechanism of adaptive resistance to aminoglycosides of Pseudomonas aeruginosa].
AB  - Exposure of Pseudomonas aeruginosa to aminoglycosides frequently selects for
      recalcitrant subpopulations exhibiting an unstable, << adaptive >> resistance to
      these antibiotics. In this study, we investigated the implication in the
      phenomenon of MexXY-OprM, an active efflux system known to export aminoglycosides
      in P. aeruginosa. Immunoblotting experiments demonstrated that the transporter
      MexY, but not the outer membrane pore OprM, was overproduced during the post-drug
      exposure adaptation period in wild-type strain PAO1. Furthermore, MexY production
      was dependent upon the degree of bacterial exposure to gentamicin (drug
      concentration). In contrast to parental strain PAO1, mutants defective in MexXY
      or in OprM were unable to develop adaptive resistance. Altogether, these results
      indicate that the resistance process requires the rapid production of MexXY and
      the interaction of these proteins with the constitutively produced component
      OprM.

PMID- 14568585
TI  - The association of serotonin with the alimentary canal of the African migratory
      locust, Locusta migratoria: distribution, physiology and pharmacological profile.
AB  - The association of serotonin with the alimentary canal of Locusta migratoria was
      investigated using immunohistochemistry and high performance liquid
      chromatography (HPLC) coupled to electrochemical detection. Serotonin-like
      immunoreactive processes were differentially distributed between and within three
      regions of the alimentary canal; the foregut, midgut and hindgut. The midgut
      possessed the most serotonin-like immunoreactive processes, while the hindgut
      contained only a few immunoreactive processes. Using HPLC coupled to
      electrochemical detection the serotonin content was highest in the midgut
      followed by the foregut and hindgut. The physiological response of the midgut to
      serotonin as well as to the combination of serotonin and proctolin was also
      examined. It was found that the application of serotonin to the midgut leads to a
      dose-dependent reduction in tonus of the circular muscles. Serotonin was also
      able to inhibit a proctolin-induced contraction of the midgut in a dose-dependent
      manner. The physiological and pharmacological properties of serotonin agonists
      and antagonists on the midgut were also investigated. The results indicate that
      alpha-methyl 5-HT was the most effective agonist leading to a 108% relaxation at
      10(-9) M compared to that caused by the same serotonin concentration. Among
      several serotonin receptor antagonists tested, mianserin was the most potent. The
      application of mianserin at 10(-5) M in combination with 5x10(-6) M serotonin
      resulted in a 66% reduction of the serotonin-induced relaxation of midgut muscle.
      The serotonin antagonist cyproheptadine was less effective leading to a 39%
      reduction of the 5x10(-6) M serotonin-induced relaxation. Ketanserin was a weak
      antagonist.

PMID- 14568588
TI  - [Hospital infection surveillance and multiresistance monitoring: role of an
      external quality control].
AB  - The "Relais Regional d'Hygiene Hospitaliere du Centre" (RHC) promotes the
      hospital infection prevention at a regional level in France, including 80
      healthcare institutions. The accuracy of antimicrobial susceptibility data
      submitted by laboratories to surveillance is essential. Since 2001, RHC imposed
      an external quality control to validate the accuracy of the data submitted by the
      laboratories that are involved in survey programs. Most laboratories are able to
      detect homogenous methicillin resistance in S. aureus, and high-level vancomycin
      resistance in E. faecalis. Nevertheless, the ability of laboratories to detect
      organisms with emerging antimicrobial resistance patterns is not optimal for (i)
      detection of heterogeneous methicillin resistance, (ii) reduced susceptibility to
      teicoplanin in a non-multiresistant S. aureus and (iii) detection of resistance
      to extended-spectrum cephalosporins. Educational program to optimize the testing
      methods has been programmed and perennially of quality control testing prior to
      accepting data from laboratory participating in surveillance system is decided.

PMID- 14568589
TI  - [Contribution of antibiotic pressure in the acquisition of methicillin-resistant
      Staphylococcus aureus (MRSA) in a university hospital].
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is a major nosocomial
      pathogen, which causes severe morbidity and mortality in hospitals. Antibiotic
      pressure is recognised as an individual risk factor in the acquisition of MRSA,
      however, some authors suggest that antibiotic use must be considered as an
      ecological and collective problem on a unit or hospital scale. The objective of
      our study was to determine whether antibiotic pressure affects the acquisition of
      MRSA. The study was conducted during 1 year (from October 2000 to September 2001)
      at Besancon hospital. The analysis was based on the research of a correlation
      between incidence of MRSA acquisition, the colonisation pressure exerted by
      imported MRSA and use of antimicrobials ineffective against MRSA at the unit
      level. Univariate analysis showed that acquired MRSA cases were significantly
      correlated with the use of all antimicrobials, as well as with the use of each
      class of antimicrobial and with colonisation pressure. In multivariate analysis,
      the stratification of the units into consumer classes allowed us to eliminate the
      scale effect of each antimicrobial class and to characterise the impact of high
      antimicrobial use compared to weak antimicrobial. The highest risks of MRSA
      acquisition were observed for beta-lactams and quinolones. This study shows that
      "MRSA acquisition" is correlated to antibiotic use and highlights the need to
      improve antibiotic usage in the control of MRSA.

PMID- 14568590
TI  - [Which betalactam antibiotic use as a marker of multiresistance in Pseudomonas
      aeruginosa?].
AB  - The determination of an indicating antibiotic for multiresistance, as methicillin
      in staphylococci, can be useful for Pseudomonas aeruginosa. Until now, the
      majority of the hygienists used ticarcillin, ceftazidim or imipenem in their
      investigations as markers of multiresistance for this species. Piperacillin has
      never been proposed for this purpose. To evaluate this choice, 2098 non
      repetitive P. aeruginosa strains collected from 15 teaching hospitals in 1997
      1999 were analysed, for eight antibiotics (ticarcillin, piperacillin, ceftazidim,
      imipenem, tobramycin, amikacin, ciprofloxacin, fosfomycin) according (i) to the
      results of the minimal inhibiting concentrations obtained by dilution in Mueller
      Hinton agar, (ii) to their susceptibility following the criteria of Comite de
      l'antibiogramme de la Societe Francaise de Microbiologie and (iii) to the
      determination of the mechanisms of resistance to the beta-lactam antibiotics. The
      low rates of sensitivity to the beta-lactam antibiotics, aminoglycosides,
      ciprofloxacin and fosfomycin were more frequent for piperacillin-resistant
      strains than for ceftazidim-resistant ones. Resistance to the other beta-lactam
      antibiotics are poor markers of multiresistance. In the light of the presented
      data, piperacillin seems to be, among the beta-lactam antibiotics, the best
      candidate as a marker of multiresistance for P. aeruginosa, followed by
      ceftazidim. This multiresistance is mainly found in strains overproducing AmpC
      cephalosporinase or transferable beta-lactamases. These mechanisms are well
      detected by resistance to piperacillin.

PMID- 14568591
TI  - [Should we screen for colonization to control the spread of multidrug resistant
      bacteria?].
AB  - Should we screen for colonization to control the spread of multidrug-resistant
      bacteria? A multidrug-resistant bacteria surveillance program was performed in
      1999 at Laennec Hospital (Nantes, France). After a 3-year period, the results
      permit us to determine the strategy to strengthen their spread. In 2001,
      Staphylococcus aureus resistant to methicillin represented 45% of the 202
      multidrug-resistant bacteria isolated. The global incidence rate per 100
      admissions remained stable between 1999 and 2001 (0.42%), but those of infections
      acquired in our institution decreased significantly from 0.27% in 1999 to 0.18%
      in 2001 (P < 0.05), particularly in medical care units (P < 0.04). In spite of
      this surveillance program and hygiene trainings, the global incidence remained
      stable during the study period, even if our action contributed to decrease the
      incidence of S. aureus resistant to methicillin acquired in our institution.
      Isolation precautions and screening for colonization policy in intensive care
      units are not sufficient to control the spread of MRB at hospital level. They
      should be strengthened by procedures for the transfer of infected or colonized
      patients and by antibiotic use control.

PMID- 14568593
TI  - [Significant decrease of rate and incidence of methicillin resistant
      Staphylococcus aureus in a French general hospital between 1999 and 2001].
AB  - In our French general hospital of 1000 hospitalization beds, a specific isolation
      for multiresistant bacteria (MRB) colonized or infected patients was set up since
      1998. To assess the impact of these recommendations, the rate and incidence of
      methicillin resistant Staphylococcus aureus (MRSA), the most important MRB
      recovered in French hospitals, were calculated for each year since 1999. All the
      strains isolated from clinical samples, except duplicates (same bacteria in the
      same patient), were included. The results were compared with the chi(2)-test.
      Between 1999 and 2001, 644 strains were isolated. MRSA rate went from 46% in 1999
      to 41% in 2000, and to 37% in 2001 (P = 0.007). In the study proposed by the
      CCLIN Paris-Nord, in April, May and June of each year, the rate of SARM was 52%
      in 1999, 43% in 2000 then 36% in 2001. The incidence per 100 admissions was 0.73
      in 1999, 0.59 in 2000 and 0.54 in 2001 (P = 0.002) and the incidence per 1000
      hospitalization days was, respectively, 0.92, 0.74, 0.67 in 1999, 2000 and 2001
      (P < 0.001). The significant decrease of the rate and incidence of SARM proved
      that the isolation policy was effective in our hospital. This decrease was
      obtained through cooperation between staff members, bacteriologists and hospital
      nosocomial infection committee members. We know that measures to prevent MRSA
      cross transmission are very difficult to maintain over a long time and we hope
      that indicators would not increase next year. The use of alcohol based hand-rub
      since May 2002 should contribute to maintain this decrease.

PMID- 14568592
TI  - [Epidemic outbreaks control involving Staphylococcus aureus with reduced
      sensitivity to glycopeptides].
AB  - This study describes two epidemic outbreaks involving Staphylococcus aureus with
      reduced sensitivity to glycopeptides, one in 2000 involving eight patients and
      the other in 2001-2002 involving 16 patients. These strains were detected
      rapidly, thanks to routine screening for the offending organisms in the
      bacteriology laboratory of our hospital. The clonal character of these strains
      was confirmed by pulsed field electrophoresis. The management of these epidemic
      outbreaks confirmed (i) the need for systematic adoption of standard precautions,
      (ii) the importance of circulating information in combating multi-resistant
      bacteria, as well as the difficulties in transferring colonised patients to
      different hospital wards, and (iii) the intermittent nature of S. aureus
      carriage, resulting in a need for prolonged surveillance of colonised and/or
      infected patients. In addition, our study underlines the value of a multi
      disciplinary approach to the management of diffusion of multi-resistant bacteria.

PMID- 14568594
TI  - [Possible implication of student nurses in the transmission of methicillin
      resistant Staphylococcus aureus during a nosocomial outbreak].
AB  - We report an outbreak of infections due to methicillin-resistant Staphylococcus
      aureus (MRSA) in a medical unit and the possible implication of student nurses in
      the dissemination of the epidemic strain. A retrospective epidemiological study
      looking for hospitalised patients colonised or infected with MRSA from the 1st of
      June to the 30th of September 2001 in the unit was conducted. An audit of
      delivered cares and a nasal screening of health care workers (HCW) was performed.
      Six patients were colonised or infected with a MRSA strain, four of them
      exhibiting a bacteremia. Six HCW had a nasal carriage of MRSA. Typing of the MRSA
      strains by pulsed field gel electrophoresis demonstrated an epidemic clone
      isolated from five of six patients, two student nurses and one HCW not implicated
      in nursing cares. This report illustrates the risk of nosocomial outbreak linked
      to cares delivered by student nurses.

PMID- 14568595
TI  - [Significant reduction of nosocomial infectious: stratified analysis of
      prevalence national studies performed in 1996 and 2001 in French north
      interegion].
AB  - BACKGROUND: In France, repeated prevalence studies of nosocomial infections (NI)
      are part of governmental plan against NI built in 1995 by the Ministry of Health.
      To evaluate strand of NI prevalence, we performed a comparative analysis of two
      successive national point-prevalence surveys occurring in 1996 and 2001 for the
      Northern France. METHOD: Comparison concerned the hospitals, which participated
      in the two studies of 1996 and 2001 in Northern France. The studies were designed
      as a point-prevalence survey on voluntary basis. For each patient, risk factors
      and presence of active NI at the day of the study were recorded on standardised
      form. Criteria of NI used were these of "100 recommendations" of CTIN and of
      CCLIN North guideline. Prevalence rate (PR) and frequency of risk factors were
      compared. The risk factors significantly linked to NI by logistic regression were
      used to build a score of five risk levels of NI (PREVARISK) allowing an adjusted
      comparison of the 2 years. RESULTS: Total of 161 hospitals participated at the
      two studies, including respectively 61 422 and 58 749 patients. Between 1996 and
      2001, crude PR of infected patients and of NI decreased respectively from 7.8% to
      7.3% and 9.0% to 8.0% (P < 10(-4)), so then relative decreases were of 6.4% and
      11.1%. In contrast, the frequency of risk factors, except surgery in the past 30
      days, significantly increased. Risk factors included in PREVARISK were: age >65
      years, immunosuppression, surgery in the past 30 days, urinary tract and central
      catheter. In patients with a low risk level (PREVARISK = 0), the relative
      decrease of infected patients and NI PR were of 17% and 19%. The decrease was not
      significant for patients with high risk level (PREVARISK >/= 3). CONCLUSION: Our
      analyses show a decrease of PR adjusted on risk factors, especially in patients
      with a low risk level. These result suggest an efficacy of program against NI in
      studied hospitals especially for patients for whom NI would be potentially
      avoidable.

PMID- 14568596
TI  - [Ecology and transmission of Mycobacterium ulcerans].
AB  - Mycobacterium ulcerans is an environmental pathogen concerning mainly the
      tropical countries; it is the causative agent of Buruli ulcer, which has become
      the third most important mycobacterial disease. In spite of water-linked
      epidemiological studies to identify the sources of M. ulcerans, the reservoir and
      the mode of transmission of this organism remain elusive. To determine the
      ecology and the mode of transmission of M. ulcerans we have set up an
      experimental model. This experimental model demonstrated that water bugs were
      able to transmit M. ulcerans by bites. In insects, the bacilli were localized
      exclusively within salivary glands, where it could both multiply contrary to
      other mycobacteria species. In another experimental study, we report that the
      crude extracts from aquatic plants stimulate in vitro the growth of M. ulcerans
      as much as the biofilm formation by M. ulcerans has been observed on aquatic
      plants. Given that the water bugs are essentially carnivorous, it is difficult to
      imagine a direct contact in the contamination of aquatic bugs and plants. It
      seems very likely that an intermediate host exists. In an endemic area of Daloa
      in Cote d'Ivoire, our observations were confirmed.

PMID- 14568597
TI  - [Lymph-node tuberculosis in patients infected or not with HIV: general
      characteristics, clinical presentation, microbiological diagnosis and treatment].
AB  - Lymph node tuberculosis is the most frequent form of extrapulmonary tuberculosis,
      especially in immunocompromised patients. We have studied patients with proven
      lymph node tuberculosis in the Department of Infectious Diseases at Pitie
      Salpetriere Hospital, Paris, between January 1997 and January 2002. Clinical
      presentation, microbiological diagnosis and treatment were analyzed in 13 HIV
      infected and 19 non-HIV infected patients. A risk factor for tuberculosis was
      present in all cases (HIV infection, immigration, life in community, poverty,
      past history of tuberculosis and IVDU). The median duration between the onset of
      symptoms and diagnosis was longer for HIV infected (2 months) compared with non
      HIV infected patients (1 month). At the time of the diagnosis, general symptoms
      were present in >50% of patients of both groups. In HIV infected patients,
      abdominal lymph node involvement was more frequent (P < 0.05). All the non-HIV
      infected and 85% of HIV infected patients had peripheral adenopathies. A
      pulmonary tuberculosis was noted in more than half of the cases (53% non-HIV and
      69% HIV patients). Inflammatory parameters and liver function tests were
      frequently abnormal in both groups. Hyponatremia was more frequent in HIV
      patients (P < 0.05). TB skin testing was more frequently positive and
      phlyctenular in non-HIV infected patients (P < 0.05). In this study, direct
      examination of the needle aspirate from infected lymph nodes was rarely positive;
      cultures were more frequently positive after biopsy compared to needle
      aspiration. The median duration of treatment was 9 months for the two groups (6
      24 months). Three HIV infected patients were infected by mycobacteria resistant
      to at least one antibiotic (isoniazid, 1; rifampicin, 1; isoniazid, streptomycin,
      etambutool, 1). All the patients recovered.

PMID- 14568598
TI  - [Acute pyelonephritis: bacteriological data and general course of germ
      resistance].
AB  - Recent bacteriological data concerning pyelonephritis mainly focus on sensitivity
      to antibiotics and virulence factors. Epidemiologically, and regardless of age
      and sex of the patients, E. coli remains the most often isolated pathogen. Only
      55% of E. coli strains (43% if isolated during a nosocomial infection) are
      sensitive to amoxicillin. Resistance to parenterally administered third
      generation cephalosporins remain exceptional. Fluoroquinolones remain very
      active, particularly in community-acquired infections (>95% sensitive strains).
      P. aeruginosa, S. aureus and enterococci are mainly isolated during nosocomial
      infections or in patients with a history of previous hospital admissions.
      Adhesion factors to urothelial cells are of uppermost importance in the
      pathogenesis of urinary infection. Adhesins G borne by fimbriae P are mainly
      concerned. Also, hemolysin is very often present in strains responsible for
      pyelonephritis. As to the search for these factors in the diagnosis of
      pyelonephritis, particularly in children, further studies are needed. The choice
      of antibiotherapy not only rests upon antibiogram data, but also upon
      pharmacological characteristics of the antibiotic.

PMID- 14568599
TI  - In vitro activity of ertapenem against anaerobes isolated from the respiratory
      tract.
AB  - Ertapenem is a novel parenteral carbapenem with a long serum half-life. Its
      spectrum of activity is similar to that of imipenem and meropenem against Gram
      positive bacteria, Enterobacteriaceae and fastidious Gram-negative bacteria but
      it is less active against Pseudomonas aeruginosa and Acinetobacter spp. Several
      studies were performed in the United States but only one European study has shown
      that ertapenem has an excellent activity against anaerobes. The objectives of the
      present study were to test the activity of ertapenem against anaerobes isolated
      prospectively from the lower and upper respiratory tracts, and to compare their
      susceptibility with that of anaerobic isolates from other body sites. Fifty-three
      isolates from the respiratory tract, as well as 50 isolates from various other
      body sites were tested with E-tests against six antibiotics. For respiratory
      isolates and for isolates from other sites, MIC 90 values (mg/l) were,
      respectively, >32 and >32 for penicillin, 0.38 and 0.75 for
      amoxicillin/clavulanate, 48 and >256 for ceftriaxone, 0.12 and 0.75 for
      ertapenem, 12 and >256 for clindamycin and 2 and 12 for moxifloxacin. The higher
      susceptibility of respiratory tract isolates was mainly due to the different
      distribution of isolated species: only three respiratory isolates but 22 other
      isolates belonged to the Bacteroides fragilis group. This study confirms the
      excellent anti-anaerobic activity of ertapenem against anaerobic isolates from
      the respiratory tract.

PMID- 14568600
TI  - [Revised prevalence of afa+ Escherichia coli strains in acute pyelonephritis of
      children].
AB  - Two hundred E. coli strains isolated from children with pyelonephritis were
      investigated for the presence of six virulence factors. The used primers
      amplified adhesin pap and sfa, toxin haemolysin (hly) and cytotoxic necrotizing
      factor 1 (cnf1) and aerobactin (aer). For afimbrial adhesin, the previously used
      set of primers could not allow to detect the newly reported afa operons (Le
      Bouguenec et al., 2001). With a new set of primers specific for the afa operon
      family the prevalence of afa+ strains increased from 3.5% to 13.5%. Combinations
      of three or more factors in a same strain were found in 48.5%. Thirty two
      different urovirulent genotypes were observed; two strains contained the six
      studied factors.

PMID- 14568601
TI  - [Antibacterial effect of two glycine betaine analogues against Escherichia coli].
AB  - Strains of enterobacteria that cause urinary tract infections are able to grow in
      urine with high tonicity. In such conditions bacterias adapt to osmotic forces by
      incorporation of osmoprotectant compounds including glycine betaine. Accumulation
      of toxic analogues in bacteria, using inducible betaine transporters, has been
      previously proposed for development of antibiotics. In this study we report
      antibacterial effect of two analogues against 82 strains of Escherichia coli
      isolated form urinary tract infections. Minimal inhibitory concentrations have
      been measured with and without osmotic stress. The betaine analogues have
      antibacterial effect against E. coli strains, but only in presence of an osmotic
      stress.

PMID- 14568603
TI  - [Liver transplantation: is it possible in HIV/HCV co-infected patients?].
AB  - The prognosis of HIV infection has been modified by antiretroviral therapy.
      However, the morbidity and the mortality of HCV co-infection increase and may be
      a major problem of health service. Up to now co-infected patients are excluded of
      transplantation due to complexity, the ethical aspects, the immunodeficiency and
      the co-infection. This study tries to estimate the feasibility in this
      population. Between December 1999 and March 2002, seven patients were
      transplanted. The average of CD4 was 332/ml; the viral load was <50 copies/ml.
      Before transplantation, no patient had experienced opportunist infection and all
      patients received antiretroviral therapy adapted to their history. The average
      follow-up is of 14 months: one patient died 3 months after transplantation, the
      other one presented a candida in oesophagus, the average of CD4 was 280/ml, and
      viral load was <50 copies/ml in five patients. A relapse of HVC was observed in
      all patients. Interferon/rivabirine therapy was proposed for four patients. Every
      patient received tacrolimus and corticoids. HAART were modified four times for
      toxicity and one time for virological failure. We observed two cases of transient
      renal insufficiency, two cases of diabetes, two cases of pancreatitis, and
      abnormalities of the respiratory mitochondrial chain in four patients. Finally,
      liver transplantation in HIV-HCV co-infected patients seems to be feasible when
      strict criteria of selection are taken into account. This still experimental
      strategy requires a multidisciplinary partnership.

PMID- 14568602
TI  - [Use of erythropoietin in the treatment of anemia induced by ribavirin/interferon
      in patients with hepatitis C].
AB  - We are presenting 20 patients with hepatitis C, who developed anemia on
      interferon alpha-2b/ribavirin treatment and were treated with recombinant human c
      alpha. Median age was 43 years (range 25-72). Four patients received previous
      treatment. Interferon-alpha-2b was given at six million units three times a week
      to 10 patients and at three million units three times a week to five patients.
      PEG-interferon-alpha-2b (80-120 mug/week) was given to five patients. The dose of
      ribavirin was 800-1200 mg/day (19 patients) and 200 mg/day (one patient with
      renal failure). Duration of an interferon/ribavirin treatment was 6-12 months.
      Baseline median hemoglobin was 13.3 g/dl (range 12.2-15.8); median hemoglobin
      nadir: 9.8 g/dl (range 8.4-11.2). On erythropoietin, the hemoglobin increased to
      median 11.7 g/dl (range 9.6-12.8). The ribavirin dose had been decreased to 800
      mg in four patients, to 600 mg in four patients, to 400 mg in one patient.
      Thirteen patients responded to interferon/ribavirin treatment, six patients (all
      genotype 1) did not. Of the 13 initial responders 11 had sustained response, one
      still under treatment and two patients relapsed. In conclusion, in our patients
      with chronic hepatitis C treated with interferon/ribavirin combination therapy,
      erythropoietin was beneficial in the treatment of ribavirin-induced anemia.

PMID- 14568604
TI  - [Real-time PCR for detection of molecular markers of resistance in Plasmodium
      falciparum].
AB  - Plasmodium falciparum drug resistance is a major problem in malaria endemic
      areas. Molecular markers and in vitro tests have been developed to study and
      monitor drug resistance. However, none used alone, can provide sufficient data
      concerning the level of drug resistance and to issue precise guideline for drug
      use policies in endemic areas. We propose real-time PCR for the simultaneous
      detection of pfcrt and pfmdr1 genes mutations. The aim of this study was not to
      provide definitive data concerning the rate of mutations in an endemic area, but
      to describe a powerful method allowing the detection of major pfmdr1 and pfcrt
      mutations.

PMID- 14568605
TI  - [Mefloquine treatment in infants and children with Plasmodium falciparum malaria:
      an efficient and well tolerated treatment].
AB  - OBJECTIVES: The aim of this study was to evaluate the efficacy and tolerance of
      mefloquine treatment in children, especially in infants of less than 15 kg, in an
      endemic area of malaria (French Guiana). METHOD: This 5-years (1996-2000)
      retrospective study included 61 children aged 6 months to 16 years who had been
      treated with mefloquine for acute Plasmodium falciparum malaria. Twenty-six of
      these children weighted less than 15 kg. The efficiency of the treatment was
      evaluated using clinical and parasitic data that had been validated according to
      the criteria of the World Health Organization (WHO). Tolerance was compared with
      the data in the medical literature. RESULTS: None of the 59 patients who were
      given the treatment correctly presented signs of early therapeutic failure as
      defined by the WHO. Apyrexia was obtained in 48 h on average (CI 95%: 39-57;
      median: 36 h). The mean time required to obtain negative parasitism was 91 h (CI
      95%: 80-101; median: 96 h) among the 51 patients in whom this was measured. Mild
      side effects were observed in 27.8% of the cases affecting mainly the digestive
      system. No differences were observed regarding efficacy or tolerance for children
      who weighed less than 15 kg. CONCLUSION: Mefloquine represents an efficient
      treatment for acute uncomplicated P. falciparum malaria in children and is well
      tolerated even in infants.

PMID- 14568606
TI  - Biophysical methods: doing more with less.

PMID- 14568607
TI  - Microfluidics in structural biology: smaller, faster em leader better.
AB  - Microfluidic technologies promise unprecedented savings in cost and time through
      the integration of complex chemical and biological assays on a microfabricated
      chip. Recent advances are making elements of this vision a reality, facilitating
      the first large-scale integration of microfluidic plumbing with biological
      assays. The power of miniaturization lies not only in achieving an economy of
      scale, but also in exploiting the unusual physics of fluid flow and mass
      transport on small length scales to realize precise and efficient assays that are
      not accessible with macroscopic tools. Diverse applications ranging from time
      resolved studies of protein folding to highly efficient protein crystal growth
      suggest that microfluidics may become an indispensable tool in biology.

PMID- 14568608
TI  - 'Cool' crystals: macromolecular cryocrystallography and radiation damage.
AB  - Macromolecular crystals commonly suffer rapid radiation damage during room
      temperature X-ray data collection. Therefore, data are now routinely collected
      with the sample held at around 100K, significantly reducing secondary radiation
      damage, and usually resulting in higher resolution and better quality data. At
      synchrotron sources, the frequent observation of radiation damage even at
      cryotemperatures has prompted the development of exciting new experiments aimed
      at characterising and reducing this damage, and using it for structure
      determination and enzymatic studies. Current research into cryotechniques seeks
      to understand the basic physical and chemical processes involved in flash-cooling
      and radiation damage, which should eventually enable the rational optimisation of
      cryoprotocols.

PMID- 14568609
TI  - Proteins in action: the physics of structural fluctuations and conformational
      changes.
AB  - Structural dynamics is essential for the biological function of proteins. Results
      from new experimental techniques should be compared with those from previous
      experiments in order to obtain a consistent picture of the physics of
      intramolecular fluctuations and conformational changes. The high intensity and
      time structure of synchrotron radiation have made possible time-resolved X-ray
      structure analysis and the determination of phonon density spectra through the
      Mossbauer effect. By combining results from Mossbauer absorption spectroscopy,
      incoherent neutron scattering, low-temperature crystallography and optical
      spectroscopy, a physical picture of protein dynamics emerges.

PMID- 14568610
TI  - Complementary approaches to structure determination of icosahedral viruses.
AB  - Few biological macromolecular complexes exhibit the combination of massive size
      and hierarchical, symmetrical architecture embodied in icosahedral viruses. X-ray
      crystallography, electron cryomicroscopy and small-angle X-ray scattering provide
      complementary approaches to studying these remarkable structures. Through a
      combined approach, progress has been made towards providing detailed structures
      of highly complex and very large viruses, and towards imaging the dynamic
      structural changes performed by viruses at key stages in their life cycles.

PMID- 14568611
TI  - TROSY in NMR studies of the structure and function of large biological
      macromolecules.
AB  - Transverse relaxation-optimized spectroscopy (TROSY), in combination with various
      isotope-labeling techniques, has opened avenues to study biomolecules with
      molecular masses of up to 1000000Da by solution NMR. Important recent
      applications of TROSY include the structure determination of membrane proteins in
      detergent micelles, structural and functional studies of large proteins in both
      monomeric form and macromolecular complexes, and investigations of intermolecular
      interactions in large complexes. TROSY improves the measurement of residual
      dipolar couplings and the detection of scalar couplings across hydrogen bonds -
      techniques that promise to further enhance the determination of solution
      structures of large proteins and oligonucleotides.

PMID- 14568612
TI  - Exchange-transferred NOE spectroscopy and bound ligand structure determination.
AB  - The exchange-transferred nuclear Overhauser effect of NMR spectroscopy provides
      information on small-molecule ligands in association with high-molecular-weight
      proteins or nucleic acids, or with biomolecular assemblies such as membranes. The
      method has proved particularly useful for the structural analysis of proton-rich,
      flexible ligands and for screening mixtures of ligands for binding activity.
      Recent analysis has established the accuracy of bound peptide structures
      determined from transferred nuclear Overhauser effect data and that
      intermolecular spin diffusion effects do not diminish the reliability of the
      structural result. New applications of the method involve systems of greater
      complexity, such as membrane-bound receptors and ribosomes. In addition, new
      experiments have been developed that exploit the transfer of other types of NMR
      signal (saturation, cross-correlation, dipolar coupling) to obtain structural
      information.

PMID- 14568613
TI  - Convergent protein synthesis.
AB  - Methods for the chemical synthesis of proteins have advanced considerably over
      the past decade. In many instances, laboratory synthesis can now be considered a
      viable alternative to ribosomal biosynthesis, especially when custom
      modifications of a protein are desired; chemical approaches guarantee virtually
      unlimited and tunable variation of the covalent structure of a polypeptide.

PMID- 14568614
TI  - Peptide and protein de novo sequencing by mass spectrometry.
AB  - Although the advent of large-scale genomic sequencing has greatly simplified the
      task of determining the primary structures of peptides and proteins, the genomic
      sequences of many organisms are still unknown. Even for those that are known,
      modifications such as post-translational events may prevent the identification of
      all or part of the protein sequence. Thus, complete characterization of the
      protein primary structure often requires determination of the protein sequence by
      mass spectrometry with minimal assistance from genomic data - de novo protein
      sequencing. This task has been facilitated by technical developments during the
      past few years: 'soft' ionization techniques, new forms of chemical modification
      (derivatization), new types of mass spectrometer and improved software.

PMID- 14568615
TI  - Carbohydrates and glycoconjugates. Glycomics: the new era of carbohydrate
      biology.

PMID- 14568616
TI  - Sulfotransferases in glycosaminoglycan biosynthesis.
AB  - Most of the sulfotransferases participating in glycosaminoglycan biosynthesis
      have now been identified. Their essential role in generating binding sites for
      proteins interacting with glycosaminoglycans is apparent. These interactions may
      influence important biological processes such as growth control, signal
      transduction, cell adhesion and lipid metabolism. Gene targeting in mice as well
      as studies in Drosophila melanogaster and Caenorhabditis elegans have shown that
      dysfunction or lack of glycosaminoglycan sulfotransferases may result in severely
      disturbed embryonic development.

PMID- 14568617
TI  - Recent advances in the structural biology of chondroitin sulfate and dermatan
      sulfate.
AB  - Recent glycobiology studies have suggested fundamental biological functions for
      chondroitin, chondroitin sulfate and dermatan sulfate, which are widely
      distributed as glycosaminoglycan sidechains of proteoglycans in the extracellular
      matrix and at cell surfaces. They have been implicated in the signaling functions
      of various heparin-binding growth factors and chemokines, and play critical roles
      in the development of the central nervous system. They also function as receptors
      for various pathogens. These functions are closely associated with the sulfation
      patterns of the glycosaminoglycan chains. Surprisingly, nonsulfated chondroitin
      is indispensable in the morphogenesis and cell division of Caenorhabditis
      elegans, as revealed by RNA interference experiments of the recently cloned
      chondroitin synthase gene and by the analysis of mutants of squashed vulva genes.

PMID- 14568618
TI  - O-mannosyl glycans: from yeast to novel associations with human disease.
AB  - In yeasts and other fungi, O-mannosyl glycans constitute a major protein
      modification that is essential for cell viability. For several decades, protein O
      mannosylation was considered a yeast-specific modification. Thus, it was
      especially interesting when it became evident that O-mannosyl glycans in mammals
      are not as rare as previously thought. O-mannosyl glycans are abundant in the
      mammalian brain and are also an abundant modification of alpha-dystroglycan, a
      component of the dystrophin-glycoprotein complex. Recently, mutations in genes
      that are or might be involved in the glycosylation of alpha-dystroglycan have
      been identified. Their association with neuromuscular diseases has focused the
      attention of different research areas on protein O-mannosylation.

PMID- 14568619
TI  - Dynamic interplay between O-GlcNAc and O-phosphate: the sweet side of protein
      regulation.
AB  - Beta-O-linked N-acetylglucosamine (O-GlcNAc) is an abundant modification of
      cytosolic and nuclear proteins that occurs in metazoans. O-GlcNAc is dynamically
      processed by a unique set of enzymes that actively add and remove the
      modification. Functionally, O-GlcNAc appears to regulate protein stability,
      subcellular localization and protein-protein interactions. The modification often
      acts in a reciprocal manner to O-phosphate modifications of proteins and together
      they can synergistically control the activity of many cellular processes.
      Recently, O-GlcNAc has been demonstrated to play a significant role in diseases
      such as diabetes, cancer and neurodegeneration. For example, the increased levels
      of O-GlcNAc that occur in diabetes are associated with decreased insulin
      responsiveness in adipocytes.

PMID- 14568620
TI  - Carbohydrate microarrays - a new set of technologies at the frontiers of
      glycomics.
AB  - Carbohydrate microarray technologies are new developments at the frontiers of
      glycomics. Results of 'proof of concept' experiments with carbohydrate-binding
      proteins of the immune system - antibodies, selectins, a cytokine and a chemokine
      - and several plant lectins indicate that microarrays of carbohydrates
      (glycoconjugates, oligosaccharides and monosaccharides) will greatly facilitate
      not only surveys of proteins for carbohydrate-binding activities but also
      elucidation of their ligands. It is predicted that both naturally occurring and
      synthetic carbohydrates will be required for the fabrication of microarrays that
      are sufficiently comprehensive and representative of entire glycomes. New leads
      to biological pathways that involve carbohydrate-protein interactions and new
      therapeutic targets are among biomedically important outcomes anticipated from
      applications of carbohydrate microarrays.

PMID- 14568621
TI  - New structural insights into carbohydrate-protein interactions from NMR
      spectroscopy.
AB  - Recently developed NMR methods have been applied to discover carbohydrate ligands
      for proteins and to identify their binding epitopes. The structural details of
      carbohydrate-protein complexes have also been examined by NMR, providing site
      specific information on the architecture, binding selectivity and plasticity of
      the carbohydrate-binding sites of the proteins. New insights into the
      conformational behaviour of free and protein-bound glycomimetics pave the way for
      the design of carbohydrate-based therapeutics. Finally, recent progress towards
      elucidating the influence of glycosylation on peptide conformation will be of key
      importance to fully understanding the role of carbohydrates in the function of
      glycopeptides.

PMID- 14568622
TI  - Classification systems for upper-limb musculoskeletal disorders in workers: a
      review of the literature.
AB  - OBJECTIVE: The purpose of this study was to provide a review of the available
      classification systems and to describe the similarities and differences in the
      structure of these systems. METHODS: Classification systems of upper limb
      musculoskeletal disorders (MSDs) were located via electronic database searches
      and researchers' files. The classification systems were compared on the disorders
      they described and on the criteria presented for each disorder. RESULTS: Twenty
      seven classification systems were found after title, abstract, or full article
      review of 1671 articles. The systems differed in the disorders they included, the
      labels used to identify the disorders, and the criteria used to describe the
      disorders. CONCLUSION: Twenty-seven classification systems were found that
      described disorders of the muscle, tendon, or nerve that may be caused or
      aggravated by work. No two systems were the same.

PMID- 14568623
TI  - The semiotics of "upper limb musculoskeletal disorders in workers".

PMID- 14568625
TI  - Should meta-analysts search Embase in addition to Medline?
AB  - It is widely accepted that meta-analysts should search multiple databases. The
      selection of databases is ideally based on the potential contribution of each
      database to the project or on the potential for bias if a database is excluded,
      as supported by research evidence. We explore whether searching Embase yields
      additional trials that influence a meta-analysis. We identified meta-analyses
      that searched Medline and Embase. A random-effects weighted mean method was used
      to estimate the intervention effect in articles indexed only in Embase compared
      with those indexed elsewhere. On average, Embase-unique trials yielded
      significantly smaller estimates by 29% (ratio of odds ratio [ROR] 0.71, 95%
      confidence interval [CI] 0.56-0.90) but influenced the pooled estimate by an
      average of only 6% (ROR 0.94, 95% CI 0.88-0.99). Searching Medline but not Embase
      risks biasing a meta-analysis by finding studies that show larger estimates, but
      their prevalence seems low enough that the risk may be slight, provided the rest
      of the search is comprehensive.

PMID- 14568626
TI  - Optimal choice of a cut point for a quantitative diagnostic test performed for
      research purposes.
AB  - Often, in epidemiologic research, classification of study participants with
      respect to the presence of a dichotomous condition (e.g., infection) is based on
      whether a quantitative measurement exceeds a specified cut point. The choice of a
      cut point involves a tradeoff between sensitivity and specificity. When the
      classification is to be made for the purpose of estimating risk ratios (RRs) or
      odds ratios (ORs), it might be argued that the best choice of cut point is one
      that maximizes the precision of estimates of the RRs or ORs. In this article, two
      different approaches for estimating RRs and ORs are discussed. For each approach,
      formulae are derived that give the mean squared error of the RR and OR estimates,
      for any choice of cut point. Based on these formulae, a cut point can be chosen
      that minimizes the mean squared error of the estimate of interest.

PMID- 14568627
TI  - Assessment of agreement of a quantitative variable: a new graphical approach.
AB  - In clinical or epidemiologic research, the measurement of variables always
      implies some degree of error. Because it is impossible to control the various
      sources of variation, the assessment of the reliability of a measurement is
      essential. Otherwise, concordance analysis must take into account the "clinical"
      interpretation of the measurement under study, because its practical usefulness
      is of central importance. In this article, we propose a new approach to assess
      the reliability of a quantitative measurement. We use a graphical approach
      familiar to statisticians and data analysts of the biomedical area, associating
      to it the useful feature of interpretation based on the proportion of concordant
      cases. We believe that the proposed graphical approach can serve as a complement,
      or as a alternative, to the Altman-Bland method for agreement analysis. It allows
      a simple interpretation of agreement that takes into account the "clinical"
      importance of the differences between observers or methods. In addition, it
      allows the analysis of reliability or agreement, by means of survival analysis
      techniques.

PMID- 14568629
TI  - Absolute benefit, number needed to treat and gain in life expectancy: which
      efficacy indices for measuring the treatment benefit?
AB  - The absolute benefit (AB) is extensively used to summarize the results of
      clinical trials. As the AB depends directly on the patient's baseline risk,
      therapeutic decisions based on AB tend to favor patients at high risk. To
      evaluate the consequences of this decision's procedure for life-long therapy, we
      compare the AB with the gain in event-free life expectancy in a simulated
      hypertensive population. Our results show that the AB goes through a maximum and
      then declines as the duration of treatment increases. The amplitude of the
      variation of AB is independent of the baseline risks but the maximum is reached
      more quickly in the high-risk patients. Considering the gain in event-free life
      expectancy, low-risk patients benefit more than high-risk patients do, at the
      expense of a longer treatment exposure. The interpretation of the AB changes
      depending on follow-up.

PMID- 14568628
TI  - Imputation of missing longitudinal data: a comparison of methods.
AB  - BACKGROUND AND OBJECTIVES: Missing information is inevitable in longitudinal
      studies, and can result in biased estimates and a loss of power. One approach to
      this problem is to impute the missing data to yield a more complete data set. Our
      goal was to compare the performance of 14 methods of imputing missing data on
      depression, weight, cognitive functioning, and self-rated health in a
      longitudinal cohort of older adults. METHODS: We identified situations where a
      person had a known value following one or more missing values, and treated the
      known value as a "missing value." This "missing value" was imputed using each
      method and compared to the observed value. Methods were compared on the root mean
      square error, mean absolute deviation, bias, and relative variance of the
      estimates. RESULTS: Most imputation methods were biased toward estimating the
      "missing value" as too healthy, and most estimates had a variance that was too
      low. Imputed values based on a person's values before and after the "missing
      value" were superior to other methods, followed by imputations based on a
      person's values before the "missing value." Imputations that used no information
      specific to the person, such as using the sample mean, had the worst performance.
      CONCLUSIONS: We conclude that, in longitudinal studies where the overall trend is
      for worse health over time and where missing data can be assumed to be primarily
      related to worse health, missing data in a longitudinal sequence should be
      imputed from the available longitudinal data for that person.

PMID- 14568630
TI  - Weighing gains and losses in criterion validity studies with test-based
      enrollment.
AB  - Criterion validity studies sometimes use designs with test-based enrollment
      schemes. In such incomplete studies, a Reference Instrument (RI) is applied to
      unequal sampling fractions of subjects previously identified as positives or
      negatives by a new Test Instrument (TI+ and TI-). Focusing on sensitivity (Se)
      and specificity (Sp), this article addresses some issues concerning the precision
      of estimates, study costs, as well as the acceptability/convenience to subjects.
      For that purpose, examples are provided whereby three indicators-statistical
      efficiency differential (deltaS), cost differential (deltaC), and (in)convenience
      differential (deltaI)-are contrasted and discussed. Although a clear, fast-and
      ready answer as to what constitutes an optimal study cannot be given, the article
      offers a rationale for weighing gains and losses. Among several scenarios, it is
      shown that an appropriately chosen incomplete study design may be as
      statistically efficient as one with a complete sampling scheme, yet is able to
      offer a ca. 15% cost reduction and about 20% fewer individuals needing to endure
      an invasive or logistically cumbersome RI. A special emphasis on the planning
      stages of an investigation is called for, precisely when the level of statistical
      precision the researcher is willing to accept can be weighed against the
      available budget and the degree of stress put on the subject that ought to be
      avoided.

PMID- 14568631
TI  - Measures of importance for economic analysis based on decision modeling.
AB  - In probabilistic economic analysis, the uncertainty concerning input parameters
      is quantified, and determines the level of uncertainty over the optimal decision.
      Researchers from a wide range of disciplines employ mathematical models to
      simulate complex processes. Common through many such disciplines is the conduct
      of importance analysis to determine those input parameters that contribute most
      to the uncertainty over the optimal decision based on the results of the
      analysis. In this study, we compare a range of potential importance measures to
      see how they compare with methods used in economic analysis. Techniques were
      classified as variance/correlation, information, probability, entropy, or
      elasticity-based measures. A selection of the most commonly used measures were
      applied to an economic model of treatment for patients with Parkinson's disease.
      Techniques were evaluated in terms of their ranking of variables, complexity, and
      interpretation.

PMID- 14568632
TI  - The impact of early transfer bias in a growth study among neonatal intensive care
      units.
AB  - BACKGROUND AND OBJECTIVE: Transfer of infants between hospitals or their
      discharge home may bias comparisons of the performance across neonatal intensive
      care units (NICUs). This study attempts to show the potential size of transfer
      bias in the context of a large cohort study and describe strategies for
      minimizing this type of bias. METHODS: To limit transfer bias in a neonatal
      growth study of extremely premature infants in six tertiary NICUs, we restricted
      eligibility to infants <30 weeks gestation at birth and substituted matched
      replacements for early transfers (infants transferred or discharged prior to day
      of life 16). RESULTS: The restriction strategy was successful, reducing the
      overall early transfer rate from 16.4 to 3.6% and the range of transfer rates
      among individual NICUs from 0.6-32.7% to 0-11.0%. Replacement by matched
      substitutes had a much smaller effect because of the small number of early
      transfers and our inability to match on all factors distinguishing early
      transfers. CONCLUSION: Sampling strategies to minimize infants lost to follow-up
      were more successful than replacement strategies in limiting transfer bias in a
      NICU growth study. Although complete elimination of bias is likely impossible,
      valid studies require efforts to minimize, quantify, and test the effect of
      transfer bias.

PMID- 14568633
TI  - Clinical prediction rule for 30-day mortality in Bjork-Shiley convexo-concave
      valve replacement.
AB  - BACKGROUND AND OBJECTIVE: We aimed to develop a clinical prediction rule for 30
      day mortality in patients undergoing Bjork-Shiley convexo-concave (BScc) valve
      replacement, based on primary valve implantation procedures. METHODS: We studied
      30-day mortality in 2,263 patients who received a BScc valve between 1979 and
      1985 in The Netherlands. A logistic regression model was constructed and
      internally validated with bootstrapping techniques. RESULTS: Predictors for
      mortality were emergency operation, coronary artery disease, mitral or double
      valve replacement, BScc implant being a reoperation, endocarditis, poor left
      ventricular function, age, concomitant tricuspid valve plasty, and aortic root
      replacement. The area under the receiver operating characteristic curve (AUC) for
      the predicted probability of death was 0.76 (95% CI 0.72-0.80). The model
      calibrated well, and had adequate discriminative ability in 195 BScc valve
      patients who underwent explantation, including 53 prophylactic explantations (AUC
      0.81, 95% CI 0.73-0.89). CONCLUSION: A prediction rule derived from BScc valve
      implantation data performed well in patients undergoing explantation. Because the
      model provides accurate individualized estimates of the risk of mortality after
      reoperation, it may be helpful for decision making in patients with BScc valves.

PMID- 14568634
TI  - An interrupted time series analysis of parenteral antibiotic use in Colombia.
AB  - A University-based hospital in Bogota, Colombia, developed and implemented an
      educational intervention to complement a new structured antibiotic order form.
      This intervention was performed after assessing the appropriateness of the
      observed antibiotic prescribing practices using a quasi-experimental study. An
      application of interrupted time series intervention analysis was conducted in
      three antibiotic groups (aminoglycosides, cephradine/cephalothin, and
      ceftazidime/cefotaxime) and their hospital weekly rate of incorrect prescriptions
      before and after the intervention. A fourth time series was defined on
      prophylactic antibiotic use in elective surgery. Preintervention models were used
      in the postintervention series to test for pre-post series level differences. An
      abrupt constant change was significant in the first, third, and fourth time
      series indicating a 47, 7.3, and 20% reduction of incorrect prescriptions after
      the intervention. We conclude that a structured antibiotic order form, coupled
      with graphic and educational interventions can improve antibiotic use in a
      university hospital.

PMID- 14568635
TI  - Reporting of somatic symptoms as a screening marker for detecting major
      depression in a population of Japanese white-collar workers.
AB  - OBJECTIVE: The objective of this study was to assess screening practices for
      detecting major depression in workers complaining of somatic symptoms. METHODS: A
      total of 1443 Japanese white-collar workers (991 men and 452 women, mean age 34
      years) completed a medical symptom checklist (major 12 somatic symptoms) and were
      diagnosed using the structured clinical interviews of the Diagnostic and
      Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). RESULTS: There
      were 42 cases (2.9%) with major depression in the total sample. Of the 902
      subjects without somatic symptoms, only one (0.1%) was identified as having major
      depression. The prevalence of the disorder was positively associated (P<.001)
      with the total number of somatic symptoms, and the area under the receiver
      operator characteristic curve was 0.92 for men and 0.81 for women, which showed
      the sensitivity and specificity of the total number of somatic symptoms for
      detecting major depression. CONCLUSION: The number of reported somatic symptoms
      is a simple and useful predictor of major depression.

PMID- 14568636
TI  - Effect of a monetary incentive on chiropractors' response rate and time to
      respond to a mail survey.

PMID- 14568637
TI  - Quality of life III: translating the science of quality-of-life assessment into
      clinical practice-an example-driven approach for practicing clinicians and
      clinical researchers.

PMID- 14568673
TI  - The immunological problem of pregnancy: 50 years with the hope of progress. A
      tribute to Peter Medawar.
AB  - This article is a tribute to the late Sir Peter Brian Medawar for his pivotal
      contribution in 1953 to the establishment of the field of Reproductive
      Immunology, with a brief and selective assessment of the progress made during the
      ensuing 50 years towards elucidation of the mechanisms responsible for the
      paradoxical survival of the conceptus as an intra-uterine allograft within the
      immunologically competent genetically alien female host. Medawar's succinct and
      stimulating theories have been central throughout the whole of this time and his
      basic conclusion, that the single most important factor ensuring the success of
      gestation is the anatomical separation of the fetus from its mother, remains
      substantially valid to this day. The extent to which other factors are of
      significance, particularly those relating to the relative roles of maternal
      adaptive and innate immune responses to the developing feto-placental unit, has
      yet to be fully defined.

PMID- 14568674
TI  - Smallpox infections during pregnancy, lessons on pathogenesis from nonpregnant
      animal models of infection.
AB  - Both vaccinated and unvaccinated women during pregnancy who contract variola
      virus, the causative agent of smallpox, suffer much higher mortality rates than
      nonpregnants. Furthermore, acute maternal smallpox leads to spontaneous abortion,
      premature termination of pregnancy and early postnatal infant mortality. The
      mechanisms governing the abortifacient activity of smallpox, as well as the
      enhanced susceptibility of gestating women to lethal disease, have remained
      largely unexamined. Experimental poxvirus infections in nonpregnant small animal
      models have revealed that T helper type 1 (TH1) cytokines promote efficient
      resolution of these infections whereas type 2 (TH2) cytokines enhance viral
      pathogenesis. These data, combined with recent understanding of how the immune
      system is modulated by pregnancy, may offer important clues as to the increased
      pathogenesis of variola in pregnant women. The aim of this review is to bring
      together the current literature on the effects of poxvirus infections in
      nonpregnant hosts, as well as the effects of pregnancy on the immune system, in
      order to develop unifying concepts that may provide insight into the pathogenesis
      of variola during pregnancy and why prior vaccination with vaccinia virus the
      live anti-variola vaccine offers less protection to pregnant women and their
      unborn children.

PMID- 14568675
TI  - Maternal and neonatal IL-4 and IFN-gamma production at delivery and 3 months
      after birth.
AB  - PROBLEM: To study the production, interrelationships and determinants of maternal
      and neonatal cytokines (IL-4 and IFN-gamma) in whole blood cultures during labor,
      after vaginal delivery and at 3 months after delivery. MAJOR RESULTS: The
      concentrations of maternal IFN-gamma and IL-4 in peripheral blood were down
      regulated at delivery compared with values 3 months postpartum. The
      concentrations of neonatal IFN-gamma and IL-4 were down-regulated at birth and
      were still at a low level 3 months later. The concentrations of IFN-gamma in
      maternal and umbilical cord blood samples correlated at delivery (r=0.43;
      P<0.03). Maternal IL-4 concentrations correlated immediately after delivery and 3
      months later (r=0.46; P<0.02) as did those of IFN-gamma (r=0.57; P<0.002).
      Neonates who were delivered at less than 40 weeks of gestation had higher IFN
      gamma concentrations 3 months after birth than those who were delivered after a
      longer duration of gestation (341 vs. 157 pg/ml; P<0.01). CONCLUSIONS: Broad
      immune activation, reflected in increased production of IL-4 and IFN-gamma, can
      be detected in women during the postpartum period. Labor-related factors had
      little effect on ranking of mothers in terms of their IL-4 or IFN-gamma levels,
      since maternal production of these cytokines correlated immediately after
      delivery and 3 months later. In neonates, the production of IFN-gamma 3 months
      after birth was dependent on gestational age at delivery.

PMID- 14568676
TI  - Interactions between the nitric oxide and prostaglandin E2 biosynthetic pathways
      in human amnion-like WISH cells.
AB  - The aim of this study was to investigate the possible relationship between
      prostaglandin (PG) and nitric oxide (NO) biosynthetic pathways in human amnion
      like WISH cells. Our results indicate that: (1) sodium nitroprusside (SNP), a NO
      donor, dose-dependently increases spontaneous prostaglandin E2 (PGE2) release
      while it inhibits the prostanoid output induced by the inflammatory cytokine,
      interleukin-1beta (IL-1beta); (2) L-arginine, the substrate of nitric oxide
      synthase (NOS), is ineffective in both conditions; (3) IL-1beta, which greatly
      enhances mRNA expression for cyclooxygenase (COX)-inducible isoform (COX-2), does
      not modify the mRNA expression for the NOS-inducible (iNOS) isoform; (4)
      indomethacin, which as expected inhibits both basal and IL-1beta-induced PGE2
      release, permits the expression of iNOS mRNA in the presence of the cytokine; (5)
      a similar permissive action on IL-1beta action is exerted by the synthetic
      steroid betamethasone, which is able to inhibit both mRNA COX-2 expression and IL
      1beta-induced PGE2 output in WISH cells; (6) exogenous PGE2 inhibits iNOS mRNA
      expression induced by indomethacin plus IL-1beta treatment; and (7) PGE2
      significantly increases intracellular adenosine 3',5'-cyclic monophosphate
      (cAMP). The results reported here suggest the existence of a relationship between
      the prostaglandinergic and nitridergic pathways in WISH cells. In particular, we
      demonstrate that exogenous NO inhibits PGE2 release evoked by IL-1beta whereas
      high levels of the prostanoid, in the presence of proinflammatory agents, exert a
      negative feed-back control on iNOS mRNA expression, possibly through a cAMP
      dependent mechanism.

PMID- 14568677
TI  - Evidence of a novel isoform of placenta growth factor (PlGF-4) expressed in human
      trophoblast and endothelial cells.
AB  - Placenta growth factor (PlGF), a homodimeric glycoprotein that is homologous to
      vascular endothelial growth factor (VEGF), is mitogenic to endothelial cells and
      protects trophoblast from apoptosis. Alternative splicing of mature mRNA gives
      rise to three known isoforms of PlGF. PlGF is expressed by human trophoblast
      during normal pregnancy, however, it is not known which isoforms are produced. We
      have utilized RT-PCR to characterize PlGF isoform expression in normal human
      trophoblast and umbilical vein endothelial cells (HUVEC). Our results show that
      PlGF-1, PlGF-2, and PlGF-3 isoforms are expressed by trophoblast and HUVECs. In
      addition, both cell types also express a novel variant of PlGF, tentatively
      termed PlGF-4, which has not been previously reported. PlGF-4 consists of the
      same sequence of PlGF-3, plus the heparin binding domain previously thought to be
      present only in PlGF-2. Presence of the heparin binding domain in PlGF-4 suggests
      that this variant would remain cell membrane-associated and thus could influence
      trophoblast and endothelial cells in an autocrine manner.

PMID- 14568678
TI  - Polymorphism in the interleukin 1 receptor antagonist gene in women with
      preeclampsia.
AB  - We have determined whether genetic variability in the gene encoding interleukin 1
      receptor antagonist (IL1Ra) contributes to individual differences in
      susceptibility to the development of preeclampsia. The study involved 133
      preeclamptic and 112 healthy control pregnant women who were genotyped for the
      variable copy number of 86-bp tandem repeats in intron 2 of the IL1Ra gene. Chi
      square analysis was used to assess genotype and allele frequency differences
      between the preeclamptic and control groups. The frequencies were also compared
      with those in the general population. The frequency of the A2 allele was 38%
      among women with preeclampsia and 33% in the healthy control women (P=0.18),
      which was close to the rate in the general population (29%). The distribution of
      the A2 alleles and pooled homozygous and heterozygous genotypes having this
      allele was significantly different between the general population and the study
      group (P=0.006), at an odds ratio of 1.51, whereas the case-control setting was
      not sufficiently powerful to show a significant association. Using population
      frequencies as a reference, an association between IL1Ra polymorphism and
      preeclampsia was apparent, although the clinical importance of this finding is
      not clear.

PMID- 14568679
TI  - The proportion of follicular fluid CD16+CD56DIM NK cells is increased in IVF
      patients with idiopathic infertility.
AB  - One-fifth of all in-vitro fertilization (IVF) patients suffer from idiopathic
      infertility. A low fertilization rate is one of the most characteristic features
      of IVF in this group, probably caused by oocyte dysfunction. We speculate that an
      altered lymphocyte profile in follicular fluid (FF) may affect oocyte function
      and thus play a role in idiopathic infertility. Therefore, we compared levels of
      lymphocyte populations present in FF of 11 patients with idiopathic infertility
      (study group) with 29 patients in the control group, i.e. severe male factor
      infertility (n=17) or tubal factor infertility (n=12). Triple color flow
      cytometry was used to discriminate between T cells and NK cell subpopulations. In
      the idiopathic infertility group, a shift from T to NK cells was observed in FF
      as compared to the control group, caused mainly by a significant higher level of
      NK cells--20.3 and 13.6% (P<0.05), respectively. This high level of NK cells was
      due to a rise of the CD16+CD56dim NK cell subset. In peripheral blood, the NK
      cell levels showed a similar although not significant trend (P=0.08). As the
      CD16+CD56dim NK cell subpopulation is known for its cytotoxic properties, this
      subpopulation may negatively affect folliculogenesis and oocyte maturation,
      reflected by a diminished fertilization rate in the idiopathic infertility group.
      An altered lymphocyte profile in FF could therefore influence fertility in these
      patients.

PMID- 14568680
TI  - Histology-related variation in the treatment and survival of patients with lung
      carcinoma in Canada.
AB  - OBJECTIVES: The aim of the study was to examine histologic differences in lung
      cancer treatment and survival, and to define recent survival trends in Ottawa,
      Canada. METHODS: From 1994 to 2000, 3,237 patients with invasive lung cancer were
      registered at the Ottawa Regional Cancer Centre (ORCC) and were followed up to 31
      December 2001. Five-year relative survival rates (RSRs) and relative excess risks
      (RERs) of dying were calculated by stage and dominant initial treatment
      modalities for major cellular histologies using a relative survival model.
      RESULTS: The overall 5-year survival rate was 14%, and female patients had
      significantly better survival. Patients with stage I and II non-small cell lung
      cancer (NSCLC) who were treated by surgery alone were more likely to survive (5
      year RSRs were 72 and 48%, respectively) than those who received other
      treatments. Patients with stage III NSCLC had a 5-year survival rate of 9% after
      chemotherapy plus radiotherapy, whereas stage IV patients who received only
      chemotherapy had better survival for up to 2 years than patients with other
      treatments. In cases of limited-stage small cell lung cancer (SCLC), survival was
      better for patients who received chemotherapy plus radiotherapy than for those
      who received only chemotherapy. CONCLUSIONS: The relatively superior survival of
      surgical patients with stage I NSCLC implies that a considerable number of
      patients have the potential to be treated successfully. The overall poor survival
      of lung cancer patients suggests a need for more national public health emphasis
      on lung cancer prevention, improved screening and early diagnosis, and better
      treatment.

PMID- 14568681
TI  - Women and small cell lung cancer: social characteristics, medical history,
      management and survival: a retrospective study of all the male and female cases
      diagnosed in Bas-Rhin (Eastern France) between 1981 and 1994.
AB  - The literature make it clear that lung cancer in women differs from that in men
      in several specific aspects. We conducted a retrospective study of the 967
      consecutive recorded patients (696 men and 91 women after exclusions) diagnosed
      with small cell lung cancers (SCLC) between 1981 and 1994 in the Bas-Rhin
      population-based cancer registry to determine if such particularities could be
      observed in SCLC. Data included demographic and social characteristics, medical
      and smoking history, management (diagnosis and treatment), hospitalisation and
      survival. The end point for survival was 31 December 1998. Women were more
      frequently single, divorced, or widowed (P=0.007) and lived more often in urban
      areas (places with more than 10,000 inhabitants) (P=0.017). They differed
      significantly from men in their tobacco exposure (P=0.0001) and non-smoking rates
      (P=0.0003) but not in clinical presentation, except for more frequently elevated
      LDH levels (P=0.02). Bone marrow biopsies were more often performed in men
      (P=0.004), but management was otherwise comparable. The mean number of
      hospitalisations (for any reason) was comparable in both sexes but women tended
      to remain hospitalised longer (P=0.057). Overall survival did not differ, but
      women older than 70 years died sooner than their male counterparts (P=0.026). Our
      study confirms that some of gender differences reported in the lung cancer
      literature exist in SCLC. Sex-related differences in LDH levels have not
      previously been reported, to our knowledge. North American and European data
      concerning survival among women and men are discordant. Whether these gender
      differences are related to a real difference between the sexes or simply to
      differential exposure to carcinogens remains to be determined.

PMID- 14568682
TI  - Aberrant messenger RNA splicing of the cytokeratin 8 in lung cancer.
AB  - Cytokeratin 8 (CK8) is one of the cytoskeletal components and shows caspase
      mediated degradation when cells undergo apoptosis. We previously reported that
      CK8 is highly expressed in non-small cell lung cancer (NSCLC) cell lines and
      increasing values of serum CK8 are significantly associated with tumor
      progression in patients with NSCLC. In this investigation, reverse transcriptase
      polymerase chain reaction (RT-PCR) analysis in lung cancer cell lines, revealed a
      shorter PCR product, which differed from the wild-type product of CK8. The
      nucleotide sequence of the shorter PCR products and genomic DNA for CK8
      demonstrated that the shorter product was an aberrantly spliced form of CK8 (AS
      CK8) which lacked a caspases cleavage site within the linker lesion in exon 5.
      The putative protein products predicted by the mRNA of AS-CK8 were demonstrated
      by Western blotting with monoclonal antibodies for CK8. In addition, AS-CK8 mRNA
      and its protein products were highly expressed in NSCLC cell lines compared with
      small-cell lung cancer (SCLC) cell lines. Tissue samples obtained from NSCLC
      patients also expressed mRNA of AS-CK8. In conclusion, we identified aberrantly
      spliced CK8 (AS-CK8) which lacked a caspases cleavage site in lung cancer cell
      lines and primary tumors of NSCLC. AS-CK8 was preferentially expressed in NSCLC,
      rather than SCLC. These findings lead to speculation that cancer cells expressing
      AS-CK8 may have a resistance to apoptosis and may perturb keratin network
      formation.

PMID- 14568683
TI  - Correlation between cyclooxygenase-2 and tumor angiogenesis in non-small cell
      lung cancer.
AB  - The role of COX-2 expression and angiogenesis of lung cancer is yet to be
      delineated. Eighty four non-small cell lung cancer (NSCLC) specimens were
      evaluated for COX-2 expression, microvessel density (MVD), and vascular
      endothelial growth factor (VEGF) expression by immunohistochemical methods. The
      relationships between COX-2 expression and MVD, VEGF expression, and survival
      time were analyzed. COX-2 expression was observed in the cytoplasm and membrane
      of the carcinoma cells, and premalignant cells. COX-2 was positive in 67 cases
      (79.8%). There was a statistically significant correlation between COX-2
      expression and tumor size, TNM stage, tumor type, VEGF expression, and vascular
      pattern with survival in univariate analysis. No significant correlation was seen
      between COX-2, VEGF expression and MVD. A lack of expression of either COX-2 or
      VEGF expression or both, however, was associated with lower MVD than the group
      with both expressed. The difference was statistically significant (P=0.005).
      Statistically significant differences were also observed according to TNM stage,
      vascular pattern, COX-2 expression, and VEGF expression. With multivariate
      analysis, only TNM stage and COX-2 expression retained their significance as
      independent predictors of survival. COX-2 expression takes part in tumor
      angiogenesis and is a significant poor prognostic factor in the surgically
      resected NSCLC. COX-2 inhibitor, either in combination therapy with other agents,
      or for chemoprevention, may be effective via suppression of angiogenesis in this
      fatal disease.

PMID- 14568684
TI  - Atypical adenomatous hyperplasia of lung: its incidence and analysis of clinical,
      glycohistochemical and structural features including newly defined growth
      regulators and vascularization.
AB  - BACKGROUND: Adenomatous hyperplasia of the peripheral lung has been suggested to
      be a preneoplastic lesion leading to peripherally localized lung carcinomas. The
      paucity of data about cellular and vascular characteristics of this lesion in
      comparison to normal lung prompted this investigation. MATERIAL AND METHODS: We
      describe results of two investigations comprising 75 cases and 70 cases,
      respectively, with atypical adenomatous hyperplasia (AAH) of the lung,
      respectively: (a) a prospective study part with thorough analysis of surgical
      lung specimens (lobes and lungs) for light microscopical detection of the lesion;
      and (b) a retrospective study part with immuno- and lectin histochemical analysis
      of AAH and non-neoplastic lung parenchyma monitoring expression of growth-related
      markers and changes in vascularization patterns. Sections of the individual cases
      were examined by an image-analyzing system including automated measurement of
      staining intensities and structure analysis. RESULTS: The prospective study part
      revealed an incidence of AAH in 2/31 cases with squamous cell carcinoma and in
      5/32 cases with adenocarcinomas. No relation to pT- or pN stages was detectable,
      high grade AAHs were seen to be close to the tumor lesions (<2 cm distance) and
      those with low grade at greater distances. Statistically significantly increased
      levels of expression of anti-apoptotic bcl-2, macrophage migration inhibitory
      factor (MIF) capable to suppress p53 activities, heparin-binding lectin,
      interleukin-2, galectin-1 and of binding sites for the endogenous lectins
      galectins-1, -3 and -7 were determined. In addition, alveolar-lining cells, which
      express these markers, formed spatial clusters, which harbor different levels of
      structural entropy. AAH displayed an increased level of vascularization
      characterized by regular size and increased number of newly formed vessels.
      INTERPRETATION: The prospective and retrospective study parts point to a close
      association of AAH with peripherally localized adenocarcinoma of the lung. AAH is
      characterized by pronounced alteration of expression of several growth-related
      markers and probably non-reversible changes in vascularization.

PMID- 14568685
TI  - The diagnostic yield of transbronchial needle aspiration in superior vena cava
      syndrome.
AB  - Superior vena cava syndrome (SVCS) requires a timely histopathological diagnosis
      for appropriate management. We prospectively evaluated the diagnostic yield and
      complications of transbronchial needle aspiration (TBNA) among patients with SVCS
      in a tertiary care university hospital. From February 1996 to April 2000, 27
      consecutive patients referred with clinical SVCS without a prior diagnosis
      underwent flexible bronchoscopy and TBNA. The ultimate diagnoses were small cell
      carcinoma (SCLC) in 15 patients, non-small cell lung carcinoma (NSCLC) in 11, and
      non-Hodgkin lymphoma in one patient. TBNA was diagnostic in all 26 patients with
      bronchogenic carcinoma, but not in lymphoma, which was subsequently diagnosed via
      thoracotomy. The overall diagnostic yield of TBNA was 96%, and the 95% confidence
      interval (CI) of diagnostic yield was 80-100%. TBNA solely provided the diagnosis
      in nine patients with NSCLC (82%), and in seven with SCLC (47%), and confirmed
      the diagnosis established via forceps biopsy in ten patients. Age, gender,
      radiological involvement and TBNA site were comparable in cases with and without
      forceps biopsy. There was no major complication related to either flexible
      bronchoscopy or TBNA. We concluded that TBNA is safe and has a high diagnostic
      yield in SVCS caused by bronchogenic carcinoma.

PMID- 14568686
TI  - MR-imaging of the brain of neurologic asymptomatic patients with large cell or
      adenocarcinoma of the lung. Does it influence prognosis and treatment?
AB  - Magnetic resonance imaging (MRI) of the brain and extensive neurological
      examination by a neurologist was performed as part of initial staging evaluation
      of 91 neurologic asymptomatic patients with large cell carcinoma or
      adenocarcinoma of the lung. Patients were followed up for at least 6 months.
      Evidence of metastatic brain disease was documented in 13 (14%) patients. Two of
      these patients were found suspective of brain metastases (BM) by the neurologist.
      The detection of BM resulted in upstaging of 1 (3%) patient in stage I/II, 4
      (21%) patients in stage IIIA and 2 (11%) patients in IIIB. Especially for
      patients in stage III this upstaging is of importance as aggressive locoregional
      treatment can be abandoned. Evaluation of the brain with MRI is a sensitive
      method of detecting BM in neurologic asymptomatic patients and is recommended as
      part of the initial staging of patients with large cell carcinoma or
      adenocarcinoma of the lung in stage III. Additional examination by the
      neurologist is of little value to provide information of the neurologic status.

PMID- 14568687
TI  - Expression of caveolin-1 is associated with poor prognosis of patients with
      squamous cell carcinoma of the lung.
AB  - BACKGROUND: Caveolin-1, as a major component of caveolae, is involved in the
      regulation of cell cycle by impacting various signaling pathways. Previous
      studies of caveolin-1 in cancer showed two contrary results. In most in vitro
      studies, caveolin-1 played a role as a tumor suppressor. On the other hand, the
      elevated expression of caveolin-1 was often reported to be associated with poor
      clinical outcome in human studies. These results indicate differential biological
      functions of caveolin-1 depending on the development and progression stage of
      cancer in vivo. METHODS: To clarify the correlation between the clinicopathologic
      profiles of pulmonary squamous cell carcinomas and the expression of caveolin-1,
      107 cases of formalin-fixed and paraffin-embedded tissues of pulmonary squamous
      cell carcinomas were immunohistochemically evaluated for the expression of
      caveolin-1 by the tissue-array method. RESULTS: Caveolin-1 was expressed in 34
      cases (31.7%) among 107 cases of pulmonary squamous cell carcinoma. The
      expression of caveolin-1 was statistically correlated with pathologic stage
      (stage I and II vs. III; P<0.001), pT (T1 and T2 vs. T3 and T4; P=0.001), and pN
      (N1 vs. N2 and N3; P=0.0143). The patients with caveolin-1 expression in
      pulmonary squamous cell carcinomas showed a poorer prognosis than those in
      caveolin-1-negative group (P=0.0345). CONCLUSION: The expression of caveolin-1 is
      significantly correlated with advanced pathologic stage and poor prognosis in
      pulmonary squamous cell carcinoma. The results of current study suggest that the
      expression level of caveolin-1 may be a candidate factor for predicting prognosis
      in patients with pulmonary squamous cell carcinoma.

PMID- 14568688
TI  - Independent value of fascin immunoreactivity for predicting lymph node metastases
      in typical and atypical pulmonary carcinoids.
AB  - Immunoreactivity for fascin, an actin-bundling protein related to cell motility,
      has been reported in breast, ovary, pancreas, skin, and non-small cell
      carcinomas, and associated with more advanced disease stage and poorer prognosis.
      Data on pulmonary neuroendocrine (NE) tumors, however, are lacking. We evaluated
      the expression of fascin by immunohistochemistry--using two different monoclonal
      antibodies--in surgical specimens of pulmonary NE tumors of all the diverse
      histological types from 128 consecutive patients recruited between 1987 and 2001,
      and investigated its relationship with the presence of lymph node metastases.
      Overall, fascin immunoreactivity was detected in 5% of 38 typical carcinoids
      (TC), 35% of 23 atypical carcinoids (AC), 83% of 40 large-cell neuroendocrine
      carcinomas (LCNEC), and 100% of 27 small-cell lung carcinomas (SCLC) (P<0.001),
      Normal NE cells or hyperplastic NE tumorlets were consistently unreactive. No
      statistically significant differences in fascin immunoreactivity were found
      between the two antibodies. In TC and AC but not high-grade NE tumors, fascin
      immunoreactivity closely correlated with the occurrence of lymph node metastases,
      the pN class and the number of involved lymph nodes (P<0.001). It was also
      significantly associated with an increased proliferative activity (Ki-67 labeling
      index >5%) (P=0.020), and with either down-regulation or altered subcellular
      compartmentalization of E-cadherin (P<0.001) and CD99 (P=0.030), two cell
      adhesion complexes in pulmonary NE tumors. At multivariate analysis, only fascin
      emerged as an independent predictor of lymph node metastases in this tumor group
      (HR 30.28; 95% confidence intervals: 1.59-574.49; P=0.023). This study indicates
      that fascin immunoreactivity may identify subsets of pulmonary carcinoid patients
      with different metastatic potential to regional lymph nodes. Targeting the fascin
      pathway could be a novel therapeutic strategy of pulmonary carcinoids.

PMID- 14568689
TI  - Surgery for young patients with lung cancer.
AB  - OBJECTIVES: To investigate the relationship between the clinical features and
      prognosis in young patients with lung cancer who underwent resection. METHODS:
      Statistical analysis was employed on sex, age, symptoms, diagnosis, treatment and
      prognosis, in 92 young cases younger than 40 years old among 930 cases with
      primary lung cancer who underwent surgery from January 1978 to December 1996.
      RESULTS: There were 92 young patients with lung cancer, accounting for 9.89% of
      the total cases. They were 71 male and 21 female patients, with the ratio of
      3.38:1. The histological types were 34 squamous cell carcinomas (37%), 30
      adenocarcinomas (33%), 26 small cell carcinomas (28%), and two large cell
      carcinomas (2%). On TNM staging, there were 30 cases in stage I (32.6%), 30 in
      stage II (32.6%) and 32 in stage III (34.8%). Lobectomy was conducted in 54
      patients (59%), pneumonectomy in 36 (39%) and wedge-shaped resection in two cases
      (2%). The rate of pneumonectomy in young patients was significantly higher than
      that of 18% in older patients (>40) with lung cancer (P<0.01). 57 patients (62%)
      received absolutely curative resection; 28 cases (30%), relatively curative
      resection; seven cases (8%), non-curative resection. The postoperative 5-year
      survival was 46% (42/92), in comparison with 34% (288/838) in patients older than
      40 receiving operation during the same period, with significant difference
      between the two groups (P<0.05). The 5-year-survivals in patients with squamous
      cell carcinoma, adenocarcinoma, small cell carcinoma and large cell carcinoma
      were 68% (23/34), 30% (9/30), 38% (10/26) and 0 (0/2), respectively. The survival
      in squamous cell cancer was markedly higher than in adenocarcinoma (P<0.01) and
      in small cell carcinoma (P<0.05). There was no significant difference between
      adenocarcinoma and small cell cancer. The 5-year-survivals in stage I, II and III
      were 63% (19/30), 53% (16/30) and 22% (7/32), respectively. There was no
      significant difference between stage I and II, while remarkable difference was
      found between stage I and III (P<0.01), and between stage II and III (P<0.05).
      The 5-year-survival in patients undergoing absolutely curative resection was 67%
      (38/57), and 14% (4/28) in patients with relatively curative resection, with
      significant difference (P<0.01). No patient survived longer than the 5th
      postoperative year in seven cases receiving non-curative resection. CONCLUSIONS:
      Young patients with lung cancer were more often seen in male than in female.
      Squamous cell carcinoma accounted for the most part, no statistical difference,
      however, compared with adenocarcinoma and small cell carcinoma. The pneumonectomy
      rate in young patients was remarkably higher than that in patients older than 40.
      The postoperative 5-year-survival in young patients was considerably higher than
      in patients older than 40 who underwent surgery during the same period. Favorable
      prognosis was seen in patients with squamous cell carcinoma and undergoing
      absolutely curative resection, while worse outcome in stage III cancer.

PMID- 14568690
TI  - Operative results of clinical stage I non-small cell lung cancer.
AB  - BACKGROUND: Clinical stage (c-stage) I non-small cell lung cancer (NSCLC) is
      generally indicated for surgery, however, surgical exploration sometimes reveals
      advanced disease, thus resulting in incomplete resection. PATIENTS AND METHODS: A
      total of 645 consecutive patients were investigated in which 347 were diagnosed
      to have c-stage IA in 347 and 298 were diagnosed to have IB disease. All cases
      underwent operation and were investigated for resectability and the cause of an
      incomplete resection. RESULTS: The c-Stage IA patients included 16.6% of T3/4 and
      10.4% of N2 whereas clinical stage IB patients included 14.4% of T3/4 and 18.8%
      of N2/3. A complete resection was performed in 594 patients (91%). In 347 c-stage
      IA patients, the complete resection rates were 93% in adenocarcinomas (235/252),
      100% in squamous cell carcinomas (76/76), and 89% in others (17/19). In 298 c
      stage IB patients, the complete resection rates were 86% in adenocarcinomas
      (141/164), 90% in squamous cell carcinomas (90/100), and 94% in others (31/33).
      The 5-year survival rates of the c-stage IA and IB patients who underwent a
      complete resection were 66.4 and 48.3%, respectively. However, the same rates
      were 18.4 and 14.7% for c-stage IA and IB patients who underwent an incomplete
      resection. The reasons for an incomplete resection in 54 patients were malignant
      pleurisy in 38 (70.4%), extranodal invasion of mediastinal nodal metastasis in
      ten (19%), an incomplete bronchial margin in three (5.6%), and ipsilateral
      pulmonary metastases in two (3.7%), and ipsilateral adrenal metastasis in one
      (1.3%). In 13% of the c-stage IB adenocarcinomas, pleural metastasis was
      discovered during thoracotomy. CONCLUSIONS: Pleural dissemination was the most
      frequent cause of an incomplete resection, and its prevalence was high in c-stage
      IB adenocarcinomas.

PMID- 14568691
TI  - A phase II trial of concurrent chemoradiation therapy followed by consolidation
      chemotherapy with oral etoposide and cisplatin for locally advanced inoperable
      non-small cell lung cancers.
AB  - We report a phase II study to evaluate the survival rate, response rate and
      toxicity of concurrent chemoradiation therapy (CCRT) followed by consolidation
      chemotherapy (CT) with oral etoposide and cisplatin for patients with locally
      advanced inoperable non-small cell lung cancer (NSCLC). Fifty-four patients with
      locally advanced inoperable NSCLC who had received no prior therapy were enrolled
      into this trial between May 1995 and December 2000. Treatment consisted of two
      cycles of concurrent CT and four cycles of consolidation CT with oral etoposide
      (50 mg/m2) on days 1-14 during the CCRT courses and on days 1-21 during the
      consolidation CT courses, plus cisplatin (75 mg/m2 i.v.) on day 1 of a 28-day
      cycle. Conventional radiotherapy (1.8 Gy/fraction, 63 Gy over 7 weeks) was
      delivered from day 1 of the CT. Fifty-two patients were evaluable for response.
      Twelve patients (22%) achieved complete responses, and 32 patients (60%) achieved
      partial responses, for an overall response rate of 82% with a median duration of
      response of 9.1 months. Forty-three per cent developed grade 4 haematological
      toxicity, 11% grade 3 or 4 oesophagitis and 7% grade 3 or 4 lung toxicity. There
      were two treatment-related deaths, one from radiation pneumonitis and the other
      from sepsis. After a median follow-up duration of 50 months (range 20-85), the
      median overall survival time was 15.3 months (95% CI, 9.7-20.8), and the 1-, 2-,
      3-, and 5 year overall survival rates were 62, 40, 30 and 16%, respectively. The
      duration of median progression-free survival was 12.3 months (95% CI, 7.4-17.3),
      and the 1-, 2-, 3-, and 5-year progression-free survival rates were 47, 40, 29
      and 23%, respectively. Thus, concurrent conventional chest radiotherapy with oral
      etoposide plus cisplatin followed by consolidation CT led to an encouraging
      survival rate and prolongation of the time to progression, with moderate toxicity
      in patients with locally advanced inoperable NSCLC.

PMID- 14568693
TI  - Heavy gas dispersion: integral models and shallow layer models.
AB  - Integral models for heavy gas dispersion approximate a dispersing cloud in terms
      of a small number of variables; each of these is ultimately a function of an
      independent variable which is usually time (instantaneous releases) or downwind
      distance (continuous releases). This type of model is used almost exclusively in
      risk assessment [HSE's risk assessment tool, RISKAT, in: Major Hazards: Onshore
      and Offshore, October 1992, pp. 607-638; Ann. Rev. Fluid Mech. 21 (1989) 317],
      but many distinct integral models exist. The code comparison exercise of Mercer
      et al. [CEA/AEA exchange agreement on external event. Comparison of heavy gas
      dispersion models for instantaneous releases: final report, Technical Report
      IR/L/HA/91/6, Health and Safety Laboratory, Sheffield, June 1991; J. Hazard.
      Mater. 36 (1994) 193] presented the results from a number of integral models in a
      common format; Mercer found that the range of predictions for some scenarios
      exceeded three orders of magnitude. Here, the TWODEE shallow layer model [J.
      Hazard. Mater. 66 (3) (1999) 211; J. Hazard. Mater. 66 (3) (1999) 227; J. Hazard.
      Mater. 66 (3) (1999) 239] is added to Mercer's code comparison exercise. The
      physical assumptions used in shallow layer models differ profoundly from those
      used in integral models and the implications of these differences for risk
      assessment are discussed. TWODEE was used to simulate four representative cases
      considered by Mercer. In terms of cloud averaged concentration (CAC) vs. centroid
      position, the present model gave predictions that were consistent with the
      integral models used by Mercer. As the model neglects horizontal diffusion for
      passive clouds, overprediction at large downwind distances was expected, but not
      generally observed.

PMID- 14568692
TI  - Phase II study of docetaxel plus enoxaparin in chemotherapy-naive patients with
      metastatic non-small cell lung cancer: preliminary results.
AB  - Activation of coagulation appears to play a role in tumor progression. This
      report describes the preliminary results of a phase II study using docetaxel plus
      enoxaparin in 15 patients with stage IV non-small cell lung cancer (NSCLC). Time
      to progression was the primary endpoint. Several surrogate markers of coagulation
      and angiogenesis were evaluated. Enoxaparin was administered at a daily dose of 1
      mg/kg (subcutaneously). The initial dose of docetaxel was 100 mg/m2, given as a
      60 min infusion every 21 days with prophylactic dexamethasone. Eight patients
      achieved an objective response (53%) and four had stable disease, with a median
      duration of 3.5 months. The median time to progression was 5 months (range, 2 to
      >15 months). The median survival was 11 months. The most frequent toxicities were
      neutropenia and asthenia. No significant bleeding or thrombotic events were
      observed. Eleven patients had elevated D-dimer plasma levels prior to therapy,
      and seven of these patients with a response or stable disease had a significant
      decline of the D-dimer during therapy. There were no consistent changes of the
      plasma levels of the angiogenic factors, except for transforming growth factor
      beta-1 (TGF-beta1). The median baseline level of TGF-beta1 prior to therapy was
      34,867 pg/ml. Twelve out of 13 patients who achieved a response or stable disease
      had a significant reduction of the TGF-beta1 levels during therapy. Enoxaparin in
      combination with chemotherapy was safe and well tolerated in patients with
      advanced NSCLC. This preliminary data suggests that enoxaparin may prolong the
      time to progression, and therefore justify the continuation of this trial.

PMID- 14568694
TI  - Calculation of minimum ignition energy of premixed gases.
AB  - The minimum ignition energy of premixed gases has been calculated by using two
      theoretical expressions and compared with the experimental data. One expression
      considers the amount of energy that the minimal flame should have, and the other
      the heat loss from the surface of the minimal flamelet. The former is a cubic
      function of the quenching distance while the latter is a quadratic function of
      quenching distance. It has been found that the latter expression gives a better
      fit to the experimental data than the former, though the discrepancy is
      considerable even for the latter expression. The calculated widths of the fronts
      of the minimal flame for various fuels were about one-order of magnitude smaller
      than the corresponding experimentally determined quenching distances, although no
      clear correlation relationship between the two quantities was found.

PMID- 14568695
TI  - Integrated risk analysis for acute and chronic exposure to toxic chemicals.
AB  - The traditional practice to assess and evaluate different types of risk in
      isolation to each other are liable to give erroneous results. Integrated risk
      assessment is an answer to overcome this problem. This paper presents the
      cumulative or integrated assessment of acute risk posed by accidental release of
      hazardous chemical (e.g. chlorine) and chronic risk induced by toxic chemicals
      (e.g. cadmium, chromium and nickel) present in the ambient environment. The
      present study has been carried out in a most simplified way to demonstrate and
      appreciate the broader context of integrated risk analysis (IRA). It has been
      observed that the inclusion of background risk factors (BRF) in individual risk
      factors (IRF) related to an industry may significantly alter the siting and
      planning strategies of that industry.

PMID- 14568697
TI  - Development of a high performance electrochemical wastewater treatment system.
AB  - In order to construct a high performance electrochemical system for practical use
      in industrial and municipal wastewater treatment, laboratory scale
      electrochemical experiments were performed to select anode materials by applying
      pulse voltage. Based on the results obtained from laboratory experiments, a pilot
      plant of electrochemical treatment system (0.3 m3 h(-1)) was successfully
      developed, in which electrocoagulation and electrooxidation processes were used.
      The performance of the treatment system was evaluated by treating domestic
      wastewater, pond water containing algae and wastewater from hog raising. As a
      result, production of hydroxyl radicals detected with p-nitrosodimethylaniline
      (RNO) at Ti/RuO(2)-TiO(2) anode was larger than with a platinum anode, and
      hydroxyl radicals were not detected at Ti anode. Moreover, a significant
      difference in electrocatalytic properties for ammonia oxidation between platinum
      and Ti/RuO(2)-TiO(2) electrodes was not observed from the cyclic voltammogram.
      The removal of T-N, T-P, NH(4)-N and COD from domestic wastewater and pond water
      containing algae was approximately 90%, while the removal of chlorophyll-a (chl
      a) of algae was approximately 100%. Although the electrochemical treatment system
      was effective on biologically treated wastewater from hog raising, the treatment
      of raw wastewater was not remarkable. Therefore, the electrochemical treatment
      system requires pretreatment when used with wastewater containing high
      concentrations of suspended solids.

PMID- 14568696
TI  - Multi-functional sorbents for the simultaneous removal of sulfur and lead
      compounds from hot flue gases.
AB  - A multi-functional sorbent is developed for the simultaneous removal of PbCl(2)
      vapor and sulfur dioxide from the combustion gases. The sorbent is tested in a
      bench-scale reactor at the temperature of 700 degrees C, using simulated flue gas
      (SFG) containing controlled amounts of PbCl(2) and SO(2) compounds. The removal
      characteristics of PbCl(2) and SO(2), individually and in combination, are
      investigated. The results show that the mechanism of capture by the sorbent is
      not a simple physical adsorption process but seems to involve a chemical reaction
      between the Ca-based sorbent and the contaminants from the simulated flue gas.
      The porous product layer in the case of individual SO(2) sorption is in a molten
      state at the reaction temperature. In contrast, the combined sorption of lead and
      sulfur compounds generates a flower-shaped polycrystalline product layer.

PMID- 14568698
TI  - Petroleum oxidation using Fenton's reagent over beach sand following a spill.
AB  - Removal and oxidation of petroleum adhered onto the beach sand after a spill over
      Guanabara Bay in Rio de Janeiro (Brazil) have been studied using Fenton's reagent
      (Fe2+ + H2O2). Jar tests were done on 5 and 20 g sand suspended in 200 ml aqueous
      solution containing iron(II) salt and hydrogen peroxide under constant stirring.
      The H2O2(g):Fe(g)2+ ratio varied from 0.5:1 to 50:1, pH was 2.0 and 6.0 and
      reaction time 1 and 3 h. Initially, the contaminated sand content of oil and
      grease (O&G) was 32 g/kg sand. The statistical analysis showed time and iron-sand
      and H2O2-iron-sand interactions to be the most significant variables, with an
      average O&G removal from the contaminated sand being just 30% after 3 h reaction.
      However, oil was removed from the sand (by up to 97%) and passed to the aqueous
      phase, making waste final disposal easier. The post-reaction analysis showed the
      supernatant to be biodegradable. Chromatographic analysis results were that the
      Fenton's reaction favored both the change and reduction of oil saturated and
      aromatic fractions.

PMID- 14568699
TI  - Evaluation of toxicity of the pesticides, chlorpyrifos and arsenic, in the
      presence of compost humic substances in aqueous systems.
AB  - An improved understanding of pesticide toxicity in natural systems can have
      important consequences for pesticide management and remediation strategies for
      contaminated areas. The interaction between humic substances extracted from
      compost natural organic matter and both organic and inorganic pesticides was
      evaluated for its effect on the toxicity of pesticides in the aqueous phase. The
      toxicity of contaminants was measured using the Microtox toxicological bioassay.
      Solutions containing concentrations ranging from 2 to 42 mg C/l of humic
      substance extracted from a South Texas compost were added to concentrations of
      the organic pesticide, chlorpyrifos, and toxicity reduction ranging from 50 to
      100% was demonstrated. Different concentrations of arsenic ranging from 0.5 to 5
      mg/l were also associated with three different concentrations of humic substances
      and the arsenic toxicity was consistently reduced by a factor of 100%. These
      results demonstrate a significant relationship between humic substance
      interactions with organic and inorganic pesticides, and pesticide toxicity in
      natural systems, and may also suggest a mechanism for pesticide toxicity
      reduction in natural waters through compost humic addition for contaminated
      groundwaters and surface waters.

PMID- 14568700
TI  - Pyrolysis kinetics of electronic packaging material in a nitrogen atmosphere.
AB  - The kinetics of pyrolysis of electronic packaging material are investigated under
      various heating rates (5, 10, 15, 20 K/min) in an inert atmosphere using a
      thermogravimetric analysis (TGA) technique. The pyrolysis characteristics of
      samples are examined by SEM, XRD, FTIR, ICP-MS and EA. The effect of heating
      condition on the surface area and pore structure of samples is discussed. Two
      reaction stages are involved for the pyrolysis of electronic packaging material
      when nitrogen is present in the carrier gas. The corresponding kinetic
      parameters, including activation energy, pre-exponential factor and reaction
      order are presented. The apparent activation energies can be divided into three
      groups. The results will be useful in developing pyrolysis or incineration
      systems for plastic waste from electronic components.

PMID- 14568701
TI  - Evaluating the applicability of a modified toxicity characteristic leaching
      procedure (TCLP) for the classification of cementitious wastes containing lead
      and cadmium.
AB  - Having the toxicity characteristic leaching procedure (TCLP) as a starting point,
      this study examined the effect of the various leaching parameters on the leaching
      of Pb and Cd from cementitious wastes. Using modified TCLP procedures, the
      parameters investigated were the acid concentration, leaching duration, particle
      size of the crushed waste, liquid to solid ratio, and the acid type. The main
      finding was that the final leachate pH controls the leachability of metals due to
      its influence on their solubility. The high alkalinity of cementitious waste
      buffers the leachate at a pH where most metals become insoluble. The TCLP was
      found to result in an unrealistic condition for cementitious wastes due to the
      high resultant leachate pH.

PMID- 14568702
TI  - Adsorption of cadmium by sulphur dioxide treated activated carbon.
AB  - Merck carbon (1.5 mm) was treated in three ways: heating from ambient temperature
      to 900 degrees C in SO(2); treatment at ambient temperature in SO(2); or
      successive treatments in SO(2) and H(2)S at ambient temperature. All samples were
      then characterised and tested as adsorbents of Cd(2+) from aqueous solution. The
      characterisation was in terms of composition by effecting ultimate and proximate
      analyses and also of textural properties by N(2) adsorption at -196 degrees C.
      Kinetics and extent of the adsorption process of Cd(2+) were studied at 25 and 45
      degrees C at pH of the Cd(2+) solution (i.e., 6.2) and at 25 degrees C also at pH
      2.0. The various treatments of the starting carbon had no significant effect on
      the kinetics of the adsorption of Cd(2+), but increased its adsorption capacity.
      The most effective treatment was heating to 900 degrees C, the adsorption in this
      case being 70.3% more than that of the starting carbon. The adsorption increased
      at 45 degrees C but decreased at pH 2.0 when compared to adsorption at 25 degrees
      C and pH 6.2, respectively.

PMID- 14568703
TI  - Recovery of EDTA and metal precipitation from soil flushing solutions.
AB  - This work studies the effectiveness of a process proposed for the recovery of
      ethylenediaminetetraacetic acid (EDTA) and metal precipitation from soil flushing
      solutions. Two series of experimental tests were carried out on two samples of a
      soil artificially contaminated with copper or lead. The metals were extracted
      from the soil by flushing with a 0.05 M aqueous solution of EDTA sodium salt (E
      Na(2)). Cu or Pb extraction efficiencies of about 95 and 98% were observed,
      respectively. The two extracted solutions were then treated to obtain EDTA
      recovery and metal precipitation from the aqueous solution. EDTA recovery was
      achieved in two steps. An initial evaporation treatment lead to reduce the
      solution volume by about 75%. This was followed by the acidification of the
      residue solution, which precipitated more than 93% of the used EDTA. The
      precipitated EDTA was removed by filtration, and was suitable for reuse after
      adding an alkaline agent. Metal precipitation from the filtered solution was
      performed using two different methods: an almost total (99.5%) Pb precipitation
      in alkaline conditions was achieved after complex destabilization through the
      sequential addition of ferric ions and sodium phosphate, while 93.6% copper
      precipitation was achieved with ferrous sulfate as a destabilization agent.

PMID- 14568704
TI  - Some comments on the paper of H. Fierz: influence of heat transport mechanisms on
      transport classification by SADT-measurement as measured by the Dewar-method.

PMID- 14568706
TI  - Impedimetric evaluation for diagnosis of Chagas' disease: antigen-antibody
      interactions on metallic electrodes.
AB  - A polypeptide chain formed by recombinant antigens, cytoplasmic repetitive
      antigen (CRA) and flagellar repetitive antigen (FRA) (CF-Chimera) of Trypanosoma
      cruzi, was adsorbed on gold and platinum electrodes and investigated by
      electrochemical impedance spectroscopy on phosphate buffer saline solutions (PBS)
      containing a redox couple. It was found that the adsorption is strongly sensitive
      to the oxide layer on the electrode surface. In the majority of the experiments
      the antigens retained their activity as observed through their interaction with
      sera from chronic chagasic patients. The results expressed in terms of the charge
      transfer resistance across the interface, indicate the viability of using the
      impedance methodology for the development of a biosensor for serological
      diagnosis of Chagas' disease.

PMID- 14568707
TI  - Antibody immobilisation on fibre optic TIRF sensors.
AB  - A study of antibody immobilisation techniques on quartz and fibre optic surfaces
      for immunosensors has been carried out. Methods of covalent antibody
      immobilisation which have not previously been applied to optical fibres were
      investigated, and compared with classical methods found in the literature.
      Preliminary experiments on covalent immobilisation methods on planar quartz
      surfaces were conducted to enable us to choose the most suitable protein
      immobilisation technique for sensor applications. The immobilisation studies were
      directed in particular towards obtaining a high density of binding sites for the
      analyte of interest. Two of the most promising methods, antibody immobilisation
      on surfaces coated with dextran based hydrogel and F(ab')-SH fragments bound to
      silanised glass, which resulted in surface densities of active sites of above
      0.45 pmol/cm2, were selected for further experiments on a fibre optic total
      internal reflection fluorescence immunosensor and gave satisfactory responses to
      changes in analyte concentrations of the order of 10(-8) M. The efficiency of
      polar organic solvents, such as dimethylsulfoxide, in dissociating the antigen
      antibody complex and hence to regenerate the immunosensor surface was also
      evaluated.

PMID- 14568708
TI  - Electrical frequency dependent characterization of DNA hybridization.
AB  - The hybridization of oligomeric DNA was investigated using the frequency
      dependent techniques of electrochemical impedance spectroscopy (EIS) and quartz
      crystal microgravimetry (QCM). Synthetic 5'-amino terminated single stranded
      oligonucleotides (ssDNA) were attached to the exposed glass surface between the
      digits of microlithographically fabricated interdigitated microsensor electrodes
      using 3-glycidoxypropyl-trimethoxysilane. Similar ssDNA immobilization was
      achieved to the surface of the gold driving electrodes of AT-cut quartz QCM
      crystals using 3-mercaptopropyl-trimethoxysilane. Significant changes in
      electrochemical impedance values (both real and imaginary components) (11%
      increase in impedance modulus at 120 Hz) and resonant frequency values (0.004%
      decrease) were detected as a consequence of hybridization of the bound ssDNA upon
      exposure to its complement under hybridization conditions. Non-complementary
      (random) sequence sowed a modest decrease in impedance and a non-detectable
      change in resonant frequency. The possibility to detect the binding state of DNA
      in the vicinity of an electrode, without a direct connection between the
      measurement electrode and the DNA, has been demonstrated. The potential for
      development of label-free, low density DNA microarrays is demonstrated and is
      being pursued.

PMID- 14568709
TI  - Patterning of photosensitive polyimide LB film and its application in the
      fabrication of biomolecular microphotodiode array.
AB  - Ultra thin film of photosensitive polyimide having benzene and sulfonyloxyimide
      moieties in the main chain was prepared using a Langmuir-Blodgett (LB) technique,
      and then micro array pattern of the polyimide LB film on a gold substrate was
      obtained by deep UV lithographic technique. In order to array cytochrome c
      molecules along the micro-patterned gold substrate, the well-characterized
      monolayer of cytochrome c was immobilized with a mixed monolayer of 11
      mercaptoundecanoic acid (11-MUDA) and decanethiol. The redox activity and
      electron transfer between cytochrome c molecular center and gold electrode
      interface for the self-assembled cytochrome c monolayer were investigated by
      cyclic voltammetry measurement. Biomolecular photodiode consisting of cytochrome
      c and green fluorescent protein (GFP) onto the patterned gold substrate was
      fabricated by self-assembly process. The integration and morphology of cytochrome
      c and GFP were studied from the measurements of atomic force microscopy (AFM) and
      fluorescence emission. Especially, current-voltage characteristics of the protein
      multilayers were investigated by scanning tunneling microscopy (STM) and its
      application in biomolecular photodiode was also examined.

PMID- 14568710
TI  - A new assay format for electrochemical immunosensors: polyelectrolyte-based
      separation on membrane carriers combined with detection of peroxidase activity by
      pH-sensitive field-effect transistor.
AB  - A new rapid immunotechnique combining separation of reactants by filtration
      through a porous membrane and potentiometric detection of the bound enzyme label
      by a pH-sensitive field-effect transistor is proposed. The complexes to be
      detected are formed by the method described earlier in (Anal. Chem. 71 (1999)
      3538), including a homogeneous binding of immunoreactants and a polyanion carrier
      (polymethacrylate) followed by heterogeneous separation on a membrane
      incorporating an immobilized polycation (poly-N-vinyl-4-ethylpyridinium). The
      proposed technique for a sensitive detection of peroxidase label is based on the
      measurement of pH changes in the optimised substrate solution containing o
      phenylenediamine, hydrogen peroxide and ascorbic acid. The antigens studied were
      herbicide atrazine and hormone testosterone. Their specific detection is realised
      via competitive binding of free and peroxidase-labelled antigens by antibodies
      integrating with a (staphylococcal protein A-polyanion) conjugate. The total
      analysis time is 20-25 min. The range of quantitative detection is 0.2-100 ng ml(
      1) for atrazine and 5-300 ng ml(-1) for testosterone. Data scatter of replicate
      tests varies from 3 to 10%. Application of protein A-polyanion conjugate allows
      to use the proposed protocol for different antigens without additional treatment
      of specific antisera.

PMID- 14568711
TI  - A rapid BOD sensing system using luminescent recombinants of Escherichia coli.
AB  - A biochemical oxygen demand (BOD) sensing system based on bacterial luminescence
      from recombinant Escherichia coli containing lux A-E genes from Vibrio fischeri
      has been developed. It was possible to use frozen cells of luminescent
      recombinants of E. coli as the bacterial reagents for measurement. Steady
      bioluminescence was observed during the incubation time between 90 and 150 min in
      the presence of a sole carbon source such as glucose, acetate, L-glutamate and
      BOD standard solution (GGA solution). This disposable bacterial reagent was
      applied to measure and detect organic pollution due to biodegradable substances
      in various wastewaters. The obtained values of this study showed a similar
      correlation with that of the conventional method for BOD determination (BOD5).
      Bacterial luminescence that was visualized with an imaging system using a charge
      coupled device (CCD) camera and a photomulti-counter demonstrated that this
      method could also be used for multi-sample detection of organic pollution due to
      biodegradable substances by using a microtiter plate. These results suggested for
      successful achievement of high-though-put detection of BOD in practical.

PMID- 14568712
TI  - Development of combinatorial bioengineering using yeast cell surface display-
      order-made design of cell and protein for bio-monitoring.
AB  - A genetic system to display proteins as their active and functional forms on the
      cell surface of yeast, Saccharomyces cerevisiae, has been exploited. Surface
      engineered (arming) cells displaying amylase or cellulase could assimilate starch
      or cellulose as the sole carbon source, although S. cerevisiae can not
      intrinsically assimilate them. Arming cells with a green fluorescent protein
      (GFP) from Aequorea victoria can emit green fluorescence from the cell surface in
      response to the environmental conditions. From these results, we attempted to
      construct a system to monitor the foreign protein production in yeast by
      simultaneous displaying the enhanced GFP (EGFP). The expression in yeast of the
      Escherichia coli beta-galactosidase-encoding gene was examined as an example of
      intracellular production and that of the human interferon-alpha (omega, IFN
      omega)-encoding gene as an example of extracellular production. Their productions
      and the simultaneous surface-display of EGFP as a reporter were controlled by the
      same promoter, GAL1. The relationship among fluorescence signals and their
      productions was evaluated. The surface-display system, unlike one using tag
      proteins, would be able to facilitate the monitoring of native protein
      productions in bioprocesses using living cells in real time by the combination of
      promoters and GFP variants.

PMID- 14568713
TI  - A novel urea sensitive biosensor with extended dynamic range based on recombinant
      urease and ISFETs.
AB  - A novel urea biosensor based on immobilised recombinant urease as sensitive
      element and ion sensitive field effect transistor as transducer was developed.
      Recombinant urease from E. coli with an increased Km was photoimmobilised in
      PVA/SbQ (poly(vinyl alcohol) containing styrylpyridinium) membrane and has
      demonstrated quite good performance as biosensitive element. Enzymatic field
      effect transistors based on such a bioselective element were studied in model
      buffer solutions. This biosensor demonstrated an extended dynamic range up to 80
      mM, a quite good reproducibility (standard deviation of the sensor responses was
      approximately 2.5%, n= 20 for urea concentration 10 mM) and a high stability.
      Such characteristics fit with the analytical requirements needed for urea control
      in plasma and liquids used during renal dialysis.

PMID- 14568714
TI  - Cl- sensitive biosensor used electrolyte-solution-gate diamond FETs.
AB  - We have investigated the electrolyte-solution-gate field effect transisitors
      (SGFETs) used hydrogen terminated (H-terminated) or partially oxygen terminated
      (O-terminated) polycrystalline diamond surface in the Cl- and Br- ionic
      solutions. The H-terminated channel SGFETs are insensitive to pH values in
      electrolyte solutions. The threshold voltages of the diamond SGFETs shift
      according to the density of Cl- and Br- ions about 30 mV/decade. One of the
      attractive biomedical applications for the Cl- sensitive SGFETs is the detection
      of chloride density in blood or in sweat especially in the case of cystic
      fibrosis. The sensitivities of Cl- and Br- ions have been lost on the partially O
      terminated diamond surface. These phenomena can be explained by the polarity of
      surface change on the H-terminated and the O-terminated surface.

PMID- 14568715
TI  - Effects of Bauxsol and biosolids on soil conditions of acid-generating mine spoil
      for plant growth.
AB  - Pot trials were conducted to examine the effects of Bauxsol and biosolids on mine
      soil conditions for plant growth. Sole application of biosolids did not
      significantly enhance the growth of the plant because the soils remained highly
      acidic with soluble concentrations of many metals in excess of toxic levels.
      Addition of Bauxsol generally resulted in an increase in biomass production by
      effectively correcting soil acidity and metal toxicity. However, sole application
      of Bauxsol did not enable meaningful establishment of the grass although the tree
      grew very well. The combination of Bauxsol and biosolids allowed the
      establishment of both the grass and the tree and therefore had the better effects
      on total biomass production, compared to the control and the sole treatments.

PMID- 14568716
TI  - Possible evidence for transport of an iron cyanide complex by plants.
AB  - Barley (Hordeum vulgare L.), oat (Avena sativa L.), and wild cane (Sorghum
      bicolor L.), were exposed to 15N-labeled ferrocyanide to determine whether these
      plant species can transport this iron cyanide complex. Plants were treated with
      ferrocyanide in a nutrient solution that simulated iron cyanide contaminated
      groundwater and soil solutions. This nutrient solution has been shown to maintain
      ferrocyanide speciation with minimal dissociation to free cyanide. Following
      treatment, all three plants showed dramatic enrichments in roots (delta 15N per
      thousand =1000-1500) and shoots (delta 15N per thousand =500). Barley and oat
      showed enrichment primarily in roots while wild cane showed a near equal
      enrichment in root and shoot tissues. Nitrogen-deficient barley plants treated
      with ferrocyanide showed a significantly greater 15N enrichment as compared to
      nitrogen-sufficient plants. While the results are suggestive of ferrocyanide
      transport by these plant species, additional study will be required to verify
      these results.

PMID- 14568717
TI  - Study of metal fractionation in river sediments. A comparison between kinetic and
      sequential extraction procedures.
AB  - The extraction kinetic of trace metals (Cd, Cu, Pb, and Zn) in river sediments by
      four extraction agents was studied. As extractants ammonium acetate, acetic acid,
      hydroxylamine and EDTA solutions were assayed. These reagents can leach the
      metals more or less selectively from several metal compartments of sediments. The
      metal leaching kinetic model permits classification of the metal species in
      labile and moderately-labile ones. The combination of two or more non specific
      reagents permits a high characterisation of metal distribution and leachability.
      The results obtained with this model in four river sediments were compared with
      data obtained by the SM&T sequential extraction procedure, in order to
      characterise the chemical nature of leached metal.

PMID- 14568718
TI  - Effects of heavy metals on population growth and metallothionein gene expression
      in the mosquito Culex quinquefasciatus, from Calcutta, India.
AB  - Major water bodies in and around the city of Calcutta (India) receive heavy metal
      contaminated effluents from industries, households, and vehicular traffic through
      sewage or drainage. We quantified concentrations of Cu, Zn, and Cd from three
      water bodies at Kalighat, Tangra, and VIP Road, respectively. The concentrations
      of these heavy metals were significantly greater in the summer than in monsoon
      when heavy downpours resulted in reduced metal concentrations. Concentrations of
      metals in the mosquito Culex quinquefasciatus also reflected such seasonal
      fluctuations. Hatchability and survivorship of C. quinquefasciatus significantly
      differed among the sites and were reduced significantly from the control.
      Exposure to heavy metals also induced MT-gene expression in C. quinquefasciatus,
      likely helping them to survive in the water bodies stressed with heavy metals. MT
      gene activity demonstrated significant variation among sites and seasons with the
      highest activity in the summer in the VIP Road population. This study suggests
      that C. quinquefasciatus could be used as an ecological indicator of heavy metal
      pollution by monitoring its MT-gene expression.

PMID- 14568719
TI  - Accumulation and distribution of platinum and rhodium in the European eel
      Anguilla anguilla following aqueous exposure to metal salts.
AB  - The platinum group metals (PGM) Pt and Rh are emitted into the environment mainly
      by catalytic exhaust gas converters of cars and by effluents of hospitals, which
      use Pt based anti-cancer drugs. However, there is still a lack of information on
      the availability of these precious metals to the biosphere. As PGM accumulate in
      sediments of aquatic ecosystems we focused our study on the uptake of the noble
      metals by European eels, Anguilla anguilla. Therefore, eels were exposed in tap
      water and humic water containing Pt(4+) and Rh(3+) at a concentration of 170 and
      260 microg/l, respectively. After an exposure period of 6 weeks the mean Pt
      levels in bile, liver, kidney and intestine of the exposed eels ranged between 68
      ng/g and 840 ng/g and the mean Rh levels between 35 ng/g and 155 ng/g whereas the
      PGM levels of the unexposed controls were below the detection limit of 50 ng/g
      for Pt and 5 ng/g for Rh. Rh was also taken up by gill and spleen. No PGM uptake
      was found for muscle and blood. The pattern of metal distribution within the eel
      differed between Pt and Rh and was dependent on the water type. Due to their
      accumulation capacity for PGM eels are suitable as accumulation indicators to
      detect PGM pollution in aquatic ecosystems.

PMID- 14568720
TI  - Mussel-based monitoring of trace metal and organic contaminants along the east
      coast of China using Perna viridis and Mytilus edulis.
AB  - Green lipped mussels, Perna viridis, and blue mussels, Mytilus edulis, were
      collected from seven locations along the east coast of China in September and
      October 2001. The mussel tissues were analyzed for metals (Ag, As, Cd, Cr, Ni,
      Pb, Se, Zn, Cu, Fe and Hg), and trace organic contaminants including
      organochlorine compounds (OCs), polycyclic aromatic hydrocarbons (PAHs; based on
      24 individual PAHs), polychlorinated biphenyls (PCBs) and petroleum hydrocarbons
      (PHCs). Maximum concentrations of Ag, As, Cd, Cr, Ni, Pb, Se, Zn, Cu, Fe and Hg
      in the mussel tissues were 0.14, 26.76, 5.31, 15.72, 4.78, 2.93, 7.40, 231.0,
      54.17, 1002 and 317.3 microg/g dry weight respectively. Levels of DDTs, PAHs,
      PCBs and PHCs in the mussel samples were 14-640, 456-3495, 1-13 ng/g and 621-2863
      microg/g dry weight, respectively. Results of this study indicated that
      contaminant levels were, in general, higher or at least comparable to those
      reported in other local or regional studies. Mussel samples collected in
      Chongming Dao in Shanghai and Jiao Zhou Wan in Qingdao had significantly higher
      levels of metal and trace organic contaminants among the seven sampling stations.
      Examination of the contaminant profiles suggests that PHCs originated from
      petrogenic sources, while both petrogenic and pyrolytic sources were important
      for PAHs. The generally high levels of metals and organochlorine compounds are
      probably the result of increasingly intense industrial activities along the east
      coast of China. An assessment of potential risks to human health due to
      consumption of the mussels was undertaken for the metals, PCBs, DDTs and
      chlordanes, and the results indicated that all metals, except Ni, could pose a
      health risk to heavy seafood consumers, while Hg appears to be of concern even
      for low level consumers.

PMID- 14568721
TI  - Probabilistic risk assessment of abalone Haliotis diversicolor supertexta exposed
      to waterborne zinc.
AB  - This paper describes a risk assessment approach that integrates predicted tissue
      concentrations of zinc (Zn) with a concentration-response relationship and leads
      to predictions of survival risk for pond abalone Haliotis diversicolor supertexta
      as well as to the uncertainties associated with these predictions. The models
      implemented include a probabilistic bioaccumulation model, which linking
      biokinetic and consumer-resource models, accounts for Zn exposure profile and a
      modified Hill model for reconstructing a dose-response profile for abalone
      exposed to waterborne Zn. The growth risk is assessed by hazard quotients
      characterized by measured water level and chronic no-observed effect
      concentration. Our risk analyses for H. diversicolor supertexta reared near
      Toucheng, Kouhu, and Anping, respectively, in north, central, and south Taiwan
      region indicate a relatively low likelihood that survival is being affected by
      waterborne Zn. Expected risks of mortality for abalone were estimated as 0.46
      (Toucheng), 0.36 (Kouhu), and 0.29 (Anping). The predicted 90th-percentiles of
      hazard quotient for potential growth risk were estimated as 1.94 (Toucheng), 0.47
      (Kouhu), and 0.51 (Anping). These findings indicate that waterborne Zn exposure
      poses no significant risk to pond abalone in Kouhu and Anping, yet a relative
      high growth risk in Toucheng is alarming. Because of a scarcity of toxicity and
      exposure data, the probabilistic risk assessment was based on very conservative
      assumptions.

PMID- 14568722
TI  - Using sequential indicator simulation to assess the uncertainty of delineating
      heavy-metal contaminated soils.
AB  - Mapping the spatial distribution of soil pollutants is essential for delineating
      contaminated areas. Currently, geostatistical interpolation, kriging, is
      increasingly used to estimate pollutant concentrations in soils. The kriging
      based approach, indicator kriging (IK), may be used to model the uncertainty of
      mapping. However, a smoothing effect is usually produced when using kriging in
      pollutant mapping. The detailed spatial patterns of pollutants could, therefore,
      be lost. The local uncertainty of mapping pollutants derived by the IK technique
      is referred to as the conditional cumulative distribution function (ccdf) for one
      specific location (i.e. single-location uncertainty). The local uncertainty
      information obtained by IK is not sufficient as the uncertainty of mapping at
      several locations simultaneously (i.e. multi-location uncertainty or spatial
      uncertainty) is required to assess the reliability of the delineation of
      contaminated areas. The simulation approach, sequential indicator simulation
      (SIS), which has the ability to model not only single, but also multi-location
      uncertainties, was used, in this study, to assess the uncertainty of the
      delineation of heavy metal contaminated soils. To illustrate this, a data set of
      Cu concentrations in soil from Taiwan was used. The results show that contour
      maps of Cu concentrations generated by the SIS realizations exhausted all the
      spatial patterns of Cu concentrations without the smoothing effect found when
      using the kriging method. Based on the SIS realizations, the local uncertainty of
      Cu concentrations at a specific location of x', refers to the probability of the
      Cu concentration z(x') being higher than the defined threshold level of
      contamination (z(c)). This can be written as Prob(SIS)[z(x')>z(c)], representing
      the probability of contamination. The probability map of Prob(SIS)[z(x')>z(c)]
      can then be used for delineating contaminated areas. In addition, the multi
      location uncertainty of an area A,delineated as contaminated based on the
      probability map of Prob(SIS)[z(x')>z(c)], can be calculated to assess the
      reliability of delineation. Multi-location uncertainty refers to the probability
      of Cu concentrations in several locations, x'(1), x'(2), em leader, x'(m,) in the
      area A, being higher than the threshold (z(c)) as denoted by
      Prob(SIS)[z(x'(1))>z(c), z(x'(2))>z(c), em leader, andz(x'(m))>z(c)] or
      Prob(SIS)[z(A)>z(c)]. The multi-location uncertainty Prob(SIS)[z(A)>z(c)],
      obtained from the SIS, can be used to assess the reliability of delineation for
      regions suspected of contamination, (A), which has been delineated as
      contaminated. Reliance on this information facilitates the decision making
      process in determining which areas are contaminated and require cleanup action.

PMID- 14568723
TI  - Geostatistical analyses and hazard assessment on soil lead in Silvermines area,
      Ireland.
AB  - Spatial distribution and hazard assessment of soil lead in the mining site of
      Silvermines, Ireland, were investigated using statistics, geostatistics and
      geographic information system (GIS) techniques. Positively skewed distribution
      and possible outlying values of Pb and other heavy metals were observed. Box-Cox
      transformation was applied in order to achieve normality in the data set and to
      reduce the effect of outliers. Geostatistical analyses were carried out,
      including calculation of experimental variograms and model fitting. The ordinary
      point kriging estimates of Pb concentration were mapped. Kriging standard
      deviations were regarded as the standard deviations of the interpolated pixel
      values, and a second map was produced, that quantified the probability of Pb
      concentration higher than a threshold value of 1000 mg/kg. These maps provide
      valuable information for hazard assessment and for decision support.

PMID- 14568724
TI  - Reliability of different sampling densities for estimating and mapping lichen
      diversity in biomonitoring studies.
AB  - Sampling requirements related to lichen biomonitoring include optimal sampling
      density for obtaining precise and unbiased estimates of population parameters and
      maps of known reliability. Two available datasets on a sub-national scale in
      Italy were used to determine a cost-effective sampling density to be adopted in
      medium-to-large-scale biomonitoring studies. As expected, the relative error in
      the mean Lichen Biodiversity (Italian acronym: BL) values and the error
      associated with the interpolation of BL values for (unmeasured) grid cells
      increased as the sampling density decreased. However, the increase in size of the
      error was not linear and even a considerable reduction (up to 50%) in the
      original sampling effort led to a far smaller increase in errors in the mean
      estimates (<6%) and in mapping (<18%) as compared with the original sampling
      densities. A reduction in the sampling effort can result in considerable savings
      of resources, which can then be used for a more detailed investigation of
      potentially problematic areas. It is, however, necessary to decide the acceptable
      level of precision at the design stage of the investigation, so as to select the
      proper sampling density.

PMID- 14568725
TI  - The effects of atmospheric nitrogen deposition in the Rocky Mountains of Colorado
      and southern Wyoming, USA-a critical review.
AB  - The Rocky Mountains of Colorado and southern Wyoming receive atmospheric nitrogen
      (N) deposition that ranges from 2 to 7 kg ha(-1) yr(-1), and some previous
      research indicates pronounced ecosystem effects at the highest rates of
      deposition. This paper provides a critical review of previously published studies
      on the effects of atmospheric N deposition in the region. Plant community changes
      have been demonstrated through N fertilization studies, however, N limitation is
      still widely reported in alpine tundra and subalpine forests of the Front Range,
      and sensitivity to changes in snow cover alone indicate the importance of climate
      sensitivity in these ecosystems. Retention of N in atmospheric wet deposition is
      <50% in some watersheds east of the Continental Divide, which reflects low
      biomass and a short growing season relative to the timing and N load in
      deposition. Regional upward temporal trends in surface water NO(3)(-)
      concentrations have not been demonstrated, and future trend analyses must
      consider the role of climate as well as N deposition. Relatively high rates of
      atmospheric N deposition east of the Divide may have altered nutrient limitation
      of phytoplankton, species composition of diatoms, and amphibian populations, but
      most of these effects have been inconclusive to date, and additional studies are
      needed to confirm hypothesized cause and effect relations. Projected future
      population growth and energy use in Colorado and the west increase the likelihood
      that the subtle effects of atmospheric N deposition now evident in the Front
      Range will become more pronounced and widespread in the future.

PMID- 14568726
TI  - The possible influence of volcanic emissions on atmospheric aerosols in the city
      of Colima, Mexico.
AB  - An elemental composition study of atmospheric aerosols from the City of Colima,
      in the Western Coast of Mexico, is presented. Samples of PM(15)-PM(2.5) and
      PM(2.5) were collected with Stacked Filter Units (SFU) of the Davis design, in
      urban and rural sites, the latter located between the City of Colima and the
      Volcan de Colima, an active volcano. Elemental analyses were carried out using
      Particle Induced X-ray Emission (PIXE). The gravimetric mass concentrations for
      the fine fraction were slightly higher in the urban site, while the mean
      concentrations in the coarse fraction were equal within the uncertainties. High
      Cl contents were determined in the coarse fraction, a fact also observed in
      emissions from the Volcan de Colima by other authors. In addition to average
      elemental concentrations, cluster analysis based on elemental contents was
      performed, with wind speed and direction data, showing that there is an
      industrial contributor to aerosols North of the urban area. Moreover, a
      contribution from the volcanic emissions was identified from the grouping of S,
      Cl, Cu, and Zn, elements associated to particles emitted by the Volcan de Colima.

PMID- 14568728
TI  - Seasonal effect on ammonia nitrogen removal by constructed wetlands treating
      polluted river water in southern Taiwan.
AB  - A pilot-scale constructed wetland (CW) system, combining a free water surface
      wetland and a subsurface wetland in series, was used to purify highly polluted
      river water. The concentrations of constituents varied seasonally. The effects of
      season-dependent parameters, such as temperature, mass loading rate and inflow
      salinity, on the removal of ammonia nitrogen (AN) in the wetland system were
      examined at a constant hydraulic loading rate, based on data from June 1998 to
      February 2000. AN removal of the CW varied cyclically with the seasons. The
      removal efficiency and the first-order volumetric removal rate constant (k(V))
      increased exponentially with water temperature, yielding a high temperature
      coefficient (theta). However, the mass removal rate decreased exponentially as
      temperature increased. These contradictory results made the actual effect of
      temperature uncertain. The inhibition of high water salinity on AN removal was
      also unclear because k(V) (as well as k(V20)) and mass removal rate were
      inversely proportional to salinity. However, mass loading rate (MLR)
      predominantly affected both the removal efficiency and the mass removal rate of
      AN, both of which were factors that explicitly determined seasonality. A power
      equation, k(V20)' alpha MLR(-n), was proposed to correct the variation of the
      mass loading rate in estimating k(V) and thus in designing a constructed wetland.

PMID- 14568727
TI  - Exploring field vegetation reflectance as an indicator of soil contamination in
      river floodplains.
AB  - This study investigated the relation between vegetation reflectance and elevated
      concentrations of the metals Ni, Cd, Cu, Zn and Pb in river floodplain soils.
      High-resolution vegetation reflectance spectra in the visible to near-infrared
      (400-1350 nm) were obtained using a field radiometer. The relations were
      evaluated using simple linear regression in combination with two spectral
      vegetation indices: the Difference Vegetation Index (DVI) and the Red-Edge
      Position (REP). In addition, a multivariate regression approach using partial
      least squares (PLS) regression was adopted. The three methods achieved comparable
      results. The best R(2) values for the relation between metals concentrations and
      vegetation reflectance were obtained for grass vegetation and ranged from 0.50 to
      0.73. Herbaceous species displayed a larger deviation from the established
      relationships, resulting in lower R(2) values and larger cross-validation errors.
      The results corroborate the potential of hyperspectral remote sensing to
      contribute to the survey of elevated metal concentrations in floodplain soils
      under grassland using the spectral response of the vegetation as an indicator.
      Additional constraints will, however, have to be taken into account, as results
      are resolution- and location-dependent.

PMID- 14568729
TI  - Effects of environmental concentrations of atrazine on hemocyte density and
      phagocytic activity in the pond snail Lymnaea stagnalis (Gastropoda, Pulmonata).
AB  - Immunotoxicological effects of environmentally relevant concentrations (10, 23,
      50, 100 microg/l) of atrazine were studied in Lymnaea stagnalis. Individual
      hemolymph sampling was performed at 0, 24, 48, 72, 96, 168, 336, 504 and 672 h
      during exposure. Every atrazine concentration induced a significant increase in
      the mean number of circulating hemocytes, without any concentration-response
      relation. A peak (1.6-fold increase) of hemocyte density was observed after 96 h
      of exposure. After 504 h, the number of hemocytes remained higher only in the
      snails exposed to the two highest concentrations. Granulocytes contributed most
      to the increase in hemocyte density in herbicide-exposed snails. Both short- (24
      and 96 h) and long-term (504 h) exposures resulted in significant inhibition of
      hemocyte phagocytic activity upon E. coli. Over the long-term, phagocytosis
      recovered for the two lowest concentrations. After 504 h of exposure, every
      herbicide level resulted in a significant reduction of reactive oxygen species
      production in E. coli-stimulated hemocytes, which was not observed for short-term
      exposures.

PMID- 14568730
TI  - Regarding the rodent sperm analysis (RSA) article in the Journal of Environmental
      Pollution.

PMID- 14568731
TI  - The greatest threat to women's health.

PMID- 14568732
TI  - Cytokines, atopy, and asthma.

PMID- 14568733
TI  - Screening sigmoidoscopy for colorectal cancer.

PMID- 14568734
TI  - Hip protectors need an evidence base.

PMID- 14568735
TI  - Lessons from the French heatwave.

PMID- 14568736
TI  - Translating research into practice--a three-paper series.

PMID- 14568737
TI  - Short postexposure prophylaxis in newborn babies to reduce mother-to-child
      transmission of HIV-1: NVAZ randomised clinical trial.
AB  - BACKGROUND: In sub-Saharan Africa, most women present late for delivery with
      unknown HIV status, which limits the use of intrapartum nevirapine to prevent
      mother-to-child transmission of HIV. We aimed to determine whether post-exposure
      prophylaxis of nevirapine plus zidovudine given to babies only reduced
      transmission of HIV more than did a regimen of nevirapine alone. METHODS: We
      randomly assigned 1119 babies of Malawian women with HIV-1 who presented late
      (ie, within 2 h of expected delivery) to either nevirapine alone or nevirapine
      and zidovudine. Both drugs were given immediately after birth: one dose of
      nevirapine (2 mg/kg weight) was given as a single dose; babies in the nevirapine
      plus zidovudine group also received zidovudine twice daily for 1 week (4 mg/kg
      weight). Infant HIV infection was determined at birth and at 6-8 weeks. Primary
      outcome was HIV infection in babies at 6-8 weeks in those not infected at birth.
      Analysis was by intention to treat. FINDINGS: The overall rate of mother-to-child
      transmission at 6-8 weeks was 15.3% in 484 babies who received nevirapine and
      zidovudine and 20.9% in 468 babies who received nevirapine only (p=0.03). At 6-8
      weeks, in babies who were HIV negative at birth, 34 (7.7%) babies who had
      nevirapine and zidovudine and 51 (12.1%) who received nevirapine only were
      infected (p=0.03)-a protective efficacy of 36%. This finding remained after
      controlling for maternal viral load and other factors at baseline. Adverse events
      were mild and of similar frequency in the two groups. INTERPRETATION:
      Postexposure prophylaxis can offer protection against HIV infection to babies of
      women who missed opportunities to be counselled and tested before or during
      pregnancy. The nevirapine and zidovudine regimen is safe and easy to implement.

PMID- 14568738
TI  - Birthweight, childhood social class, and change in adult blood pressure in the
      1946 British birth cohort.
AB  - BACKGROUND: The negative effect of birthweight on systolic blood pressure has
      been suggested to be initiated in utero and amplified with age. We aimed to
      investigate this hypothesis. METHODS: A sample of 3634 people from a birth cohort
      study of men and women born in Britain in 1946 were included in analyses. Cohort
      members have been contacted regularly since birth, and systolic and diastolic
      blood pressures were measured at ages 36, 43, and 53 years. Multilevel models,
      with blood pressure as a repeated outcome, were used to test the amplification
      hypothesis and to compare results for birthweight with those for childhood social
      class. FINDINGS: Considering both men and women together, a consistent negative
      association between birthweight and systolic blood pressure was noted from age 36
      to 53 years, but no evidence was recorded of substantial amplification with age.
      A 1 kg higher birthweight was associated with a slower mean increase in systolic
      blood pressure by -0.4 mm Hg (95% CI -1.3 to 0.4; p=0.3) per 10-year increase in
      age. Birthweight was not associated with diastolic blood pressure at any age.
      People from a manual social class in childhood had higher systolic and diastolic
      blood pressure than did those from a non-manual class. The effect on systolic
      blood pressure rose with age, by 1.0 mm Hg (95% CI 0.1 to 2.0; p=0.03) per 10
      years, but was largely accounted for by current body-mass index, which was an
      increasingly strong determinant of blood pressure. INTERPRETATION: These findings
      suggest that weight control throughout life is key to prevention of raised blood
      pressure during middle age. Understanding the link between the early childhood
      socioeconomic environment and adult obesity could make this strategy more
      effective.

PMID- 14568739
TI  - Ectopic pregnancy: which side to operate?

PMID- 14568740
TI  - Clinical importance of neutralising antibodies against interferon beta in
      patients with relapsing-remitting multiple sclerosis.
AB  - BACKGROUND: Interferon beta is the first-line treatment for relapsing-remitting
      multiple sclerosis, but the drug can induce neutralising antibodies against
      itself, which might reduce effectiveness. We aimed to assess the clinical effect
      of neutralising antibodies. METHODS: We measured neutralising antibodies every 12
      months for up to 60 months in 541 patients with multiple sclerosis, randomly
      selected from all patients who started treatment with interferon beta between
      1996 and 1999. Patients left the study if they changed or discontinued therapy.
      Antibodies were measured blindly, using antiviral neutralisation bioassays with
      high, medium, and low sensitivity, and with different neutralising capacities as
      cutoff value for definition of a neutralising-antibody-positive result. FINDINGS:
      Patients developed neutralising antibodies independent of age, sex, disease
      duration, and progression index at start of treatment. Relapse rates were
      significantly higher during antibody-positive periods (0.64-0.70) than they were
      during antibody-negative periods (0.43-0.46; p<0.03). When comparing the number
      of relapses in the neutralising-antibody-positive and neutralising-antibody
      negative periods we found odds ratios in the range 1.51 to 1.58 (p<0.03). Time to
      first relapse was significantly increased by 244 days in patients who were
      antibody-negative at 12 months (log rank test 6.83, p=0.009). During this short
      term study, presence of neutralising antibodies did not affect disease
      progression measured with the expanded disability status scale. INTERPRETATION:
      Our findings suggest that the presence of neutralising antibodies against
      interferon beta reduces the clinical effect of the drug. In patients who are not
      doing well on interferon beta, the presence of such antibodies should prompt
      consideration about change of treatment.

PMID- 14568742
TI  - A bad dose of the 'flu.

PMID- 14568741
TI  - Association between antenatal cytokine production and the development of atopy
      and asthma at age 6 years.
AB  - BACKGROUND: Various lines of evidence suggest that antenatal factors are
      important in determining susceptibility to atopy and asthma. One possible
      mechanism is cytokines, production of which in the placenta is high throughout
      gestation and which protect placental integrity via control of local
      immunological homoeostasis. We investigated antenatal cytokine concentrations in
      a prospective birth cohort, intensively monitored for atopy and asthma outcomes
      at age 6 years. METHODS: Cryopreserved cord-blood serum samples from 407 children
      were assayed for interleukins 4, 5, 6, 10, 12, and 13, interferon gamma, and
      tumour necrosis factor alpha (TNFalpha). Associations between family, antenatal,
      and perinatal factors, cord-blood cytokine concentrations, and atopy or asthma
      outcomes were analysed by logistic regression. Causal effects of cytokines on
      outcomes were estimated by propensity scores based on family, antenatal, and
      perinatal factors. FINDINGS: Detectable cord-blood concentrations of interleukin
      4 and interferon gamma were each associated with lower risk of physician
      diagnosed asthma (adjusted odds ratios 0.60 [95% CI 0.37-0.99] and 0.60 [0.37
      0.97] respectively), current asthma (0.59 [0.33-1.00] and 0.39 [0.22-0.71]), and
      current wheeze (0.55 [0.32-0.93] and 0.52 [0.31-0.90]) and atopy (sensitisation
      to some inhalant allergens) outcomes at 6 years. High concentrations of TNFalpha
      were associated with lower risk of atopy but not with asthma risk. These
      associations were broadly unaltered by propensity-score adjustment. Maternal
      smoking was associated with higher risk of both wheeze at 6 years and lower
      concentrations of interleukin 4 and interferon gamma in cord blood.
      INTERPRETATION: The mechanism underlying attenuated T-helper-1/T-helper-2
      cytokine production in high-risk children also apparently operates in control of
      cytokine production in the fetoplacental unit. The finding that this mechanism is
      dysregulated by maternal smoking suggests it is a target for antenatal
      environmental factors relevant to asthma aetiology.

PMID- 14568743
TI  - 3-dimensional colour power angiography for staging human placental development.
AB  - Maldevelopment of placental villous trees and their blood vessels results in
      impaired fetal growth, which can greatly compromise fetal, neonatal, childhood,
      and adulthood health. There are no means of directly assessing such
      maldevelopment. We have applied a new technique of imaging (colour power
      angiography [CPA]) with 3-dimensional reconstruction to assess directly villous
      development in human pregnancy in vivo in 20 uncomplicated pregnancies from 13 to
      38 weeks' gestation. The chronology of villous trees was much the same in 3
      dimensional CPA, scanning electron micrography, and classical histology from
      controls matched by age. This approach provides a unique opportunity to examine
      normal placental development directly, and should provide the bases for real-time
      investigation of placental pathology and a robust method for diagnosis and
      surveillance during pregnancy.

PMID- 14568745
TI  - Stroke.
AB  - Stroke is a major public-health burden worldwide. Prevention programmes are
      essential to reduce the incidence of stroke and to prevent the all but inevitable
      stroke epidemic, which will hit less developed countries particularly hard as
      their populations age and adopt lifestyles of the more developed countries.
      Efficient, effective, and rapid diagnosis of stroke and transient ischaemic
      attack is crucial. The diagnosis of the exact type and cause of stroke, which
      requires brain imaging as well as traditional clinical skills, is also important
      when it will influence management. The treatment of acute stroke, the prevention
      and management of the many complications of stroke, and the prevention of
      recurrent stroke and other serious vascular events are all improving rapidly.
      However, stroke management will only be most effective when delivered in the
      context of an organised, expert, educated, and enthusiastic stroke service that
      can react quickly to the needs of patients at all stages from onset to recovery.

PMID- 14568744
TI  - Rickettsia sibirica infection in members of scientific expeditions to northern
      Asia.
AB  - The risk of acquiring North Asian tick typhus (infection by Rickettsia sibirica)
      during travel to regions of Asia where this disease is endemic is unknown. We
      investigated prospectively 13 paleontologists on expedition to Mongolia. Four
      paleontologists had acute illness characterised by fever, rash, headache, and
      lymphadenopathy. All had IgM and IgG antibodies to R sibirica. Paleontologists
      with no illness and people who went on expeditions in other parts of the world
      did not have antibodies to R sibirica. Only two of the four infected persons were
      aware of tick bites. Travellers to regions endemic for R sibirica are at risk of
      contracting North Asian tick typhus even in the absence of recognised tick-bites.

PMID- 14568746
TI  - Bone-marrow fibrin-ring granuloma.

PMID- 14568747
TI  - From best evidence to best practice: effective implementation of change in
      patients' care.
AB  - Major difficulties arise when introducing evidence and clinical guidelines into
      routine daily practice. Data show that many patients do not receive appropriate
      care, or receive unnecessary or harmful care. Many approaches claim to offer
      solutions to this problem; which ones are as yet the most effective and efficient
      is unclear. We aim to provide an overview of present knowledge about initiatives
      to changing medical practice. Substantial evidence suggests that to change
      behaviour is possible, but this change generally requires comprehensive
      approaches at different levels (doctor, team practice, hospital, wider
      environment), tailored to specific settings and target groups. Plans for change
      should be based on characteristics of the evidence or guideline itself and
      barriers and facilitators to change. In general, evidence shows that none of the
      approaches for transferring evidence to practice is superior to all changes in
      all situations.

PMID- 14568748
TI  - Helicobacter pylori virulence factors--one part of a big picture.
AB  - CONTEXT: At least half the world's population is infected with Helicobacter
      pylori, although only 10-20% of carriers develop gastric diseases, ranging from
      ulcer to MALT-lymphoma and adenocarcinoma (MALT is mucosa-associated lymphoid
      tissue). The clinical outcome of H pylori infection is determined by a complex
      interaction of environmental influences and host and microbial virulence factors.
      H pylori genotypes carrying the babA2 gene, encoding a bacterial adhesin
      mediating interaction with gastric epithelial cells, have enhanced pathogenicity.
      Moreover, coexistence of babA2 with other bacterial virulence factors further
      worsens clinical outcomes. STARTING POINT: To further elucidate the clinical
      relevance of babA2-genopositive H pylori strains, Carlo-Frederico Zambon and
      colleagues analysed the association of babA2 genotypes with gastritis,
      gastroduodenal ulcer disease, or intestinal metaplasia in 167 infected Italian
      individuals. The coexistence of babA2 with other potentially disease-related H
      pylori genes, such as cagA, vacA, or oipA, correlated with clinical outcome. 36%
      of H pylori strains were babA2(-) genopositive, and abundance of babA2 was
      associated with the genomic presence of the other potential virulence-factor
      genes. H pylori strains carrying babA2, cagA, and the vacA genotype s1m1 were
      associated with the highest risk of developing intestinal metaplasia, whereas
      this condition was rarely (<10%) associated with strains with a cagA-, babA2-,
      vacA s2m2 genotype. Whilst the risk of developing more serious gastric lesions
      increased as the number of virulence factor genes accumulated in a given H pylori
      strain, there was no indication of any one specific bacterial gene-pattern being
      associated with a particular clinical disease. WHERE NEXT? Identifying the
      factors responsible for the enhanced pathogenicity of H pylori leading to
      development of life-threatening diseases in a subset of infected individuals is a
      mandatory task for the future. Identification of virulence-associated H pylori
      genes and investigation of their clinical relevance in large prospective studies
      will help to define such strains with increased pathogenicity. The value of H
      pylori genotypes as predictors of disease outcome is limited, because the
      pathogenic impact of bacterial virulence factors is greatly influenced by
      coexisting environmental and host factors.

PMID- 14568749
TI  - New variant famine: AIDS and food crisis in southern Africa.
AB  - Southern Africa is undergoing a food crisis of surprising scale and novelty. The
      familiar culprits of drought and mismanagement of national strategies are
      implicated. However, this crisis is distinct from conventional drought-induced
      food shortages with respect to those vulnerable to starvation, and the course of
      impoverishment and recovery. We propose that these new aspects to the food crisis
      can be attributed largely to the HIV/AIDS epidemic in the region. We present
      evidence that we are facing a new variant famine. We have used frameworks drawn
      from famine theory to examine the implications. HIV/AIDS has created a new
      category of highly vulnerable households--namely, those with ill adults or those
      whose adults have died. The general burden of care in both AIDS-affected and non
      AIDS-affected households has reduced the viability of farming livelihoods. The
      sensitivity of rural communities to external shocks such as drought has
      increased, and their resilience has declined. The prospects for a sharp decline
      into severe famine are increased, and possibilities for recovery reduced.

PMID- 14568750
TI  - Monitoring of mortality rates in primary care.

PMID- 14568751
TI  - Monitoring of mortality rates in primary care.

PMID- 14568753
TI  - Importance of medicine-related problems as risk factors.

PMID- 14568754
TI  - The euthanasia law in Belgium and the Netherlands.

PMID- 14568755
TI  - Addiction myths?

PMID- 14568756
TI  - Addiction myths?

PMID- 14568757
TI  - Oral contraceptive and smoking mortality.

PMID- 14568759
TI  - Genetic influence of hormone-replacement therapy on venous thromboembolism.

PMID- 14568760
TI  - Edmonton's islet success has indeed been replicated elsewhere.

PMID- 14568761
TI  - Smoking, iron, and tuberculosis.

PMID- 14568762
TI  - Singular loyalties.

PMID- 14568763
TI  - Control of tuberculosis in India.

PMID- 14568765
TI  - The human thermostat.

PMID- 14568767
TI  - The anorexia talking?

PMID- 14568769
TI  - Teen dreams.

PMID- 14568772
TI  - Genotyping of cytochrome p450 isoform genes is useful for forensic identification
      of cadaver.
AB  - Tailor-made medical treatment based on the polymorphism of genes encoding drug
      metabolizing enzymes has been advocated and is being tried on an experimental
      basis at numerous centers. If DNA polymorphism analysis becomes routine in tailor
      made medical treatment, it will be very useful in forensic identification. In
      this study, we determined the genotype frequencies of five p450 (CYP) isoform
      genes, CYP1A2, CYP2D6, CYP2E1, CYP2C9 and CYP2C19 in 196 Japanese individuals to
      evaluate their forensic usefulness. These genes encode the most important enzymes
      among the CYP superfamily that metabolize clinically used drug. The frequency of
      each allele agreed well with those reported previously and their genotype
      frequencies did not deviate from those expected from Hardy-Weinberg equilibrium.
      CYP2C subfamilies such as CYP2C9 and CYP2C19 on chromosome 10 showed high
      sequence homology, as high as over 95% in the regions flanking polymorphic sites.
      Although 3240 genotype combinations of these five CYP isoform genes are
      theoretically possible, 101 combinations were detected in this study. The
      genotype frequencies of these five isoform genes excluded their linkage. The
      following two genotype combinations showed the highest frequency of 0.036:
      CYP1A2*1A/*1A, CYP2D6*1/*10, CYP2E1*1/*1, CYP2C9*1/*1 and CYP2C19*1/*1 and
      CYP1A2*1A/*1C, CYP2D6*1/*10, CYP2E1*1/*1, CYP2C9*1/*1 and CYP2C19*1/*1. Thus,
      genotyping of CYP isoform genes should be useful in forensic identification.

PMID- 14568771
TI  - Utilization of lectin-histochemistry in forensic neuropathology: lectin staining
      provides useful information for postmortem diagnosis in forensic neuropathology.
AB  - We have investigated the deposition of glycoconjugates in human brain tissue with
      or without brain disorders. In this review we describe the application of lectin
      histochemistry techniques to forensic neuropathology. Lectin staining is able to
      reveal several kinds of carbohydrate-related depositions in addition to the
      conventional degenerative changes including senile plaques, neurofibrillary
      tangles and corpora amylacea. The senile plaques and neurofibrillary tangles were
      clearly stained by Con A, PSA and GSI lectins, the corpora amylacea which is
      relevant to repeated brain hypoxia and mitochondrial damage was also easily
      detected by these and many other kinds of lectins. Amorphous spaces were detected
      around blood vessels and independently from blood vessels by lectin staining in
      the white matter from patients with brain disorders or severe edema. The white
      matter lesions were not considered relevant for forensic pathology, until a large
      group of cerebral white matter lesions were detected in the elderly with
      increasing frequency by modern neuro-imaging methods. The spherical deposits were
      newly detected by lectin staining in the molecular layer of the dentate gyrus of
      the hippocampal formation chiefly from patients with schizophrenia or cognitive
      dysfunctions.

PMID- 14568773
TI  - Fatal accidental burns in married women.
AB  - Burning incidents amongst women are a major concern in India as it has become
      pervasive throughout all social strata and geographical areas. They may be
      homicidal, suicidal or accidental in nature. Here, in the study, the main
      objective is to present the different epidemiological and medicolegal aspects of
      accidental burns in the married women. In a cohort of 152 burned wives, 70 (46%)
      were accidental victims and these cases were analyzed accordingly for their
      different medicolegal and epidemiological aspects. Data were collected from
      personal interview and from examining the different documents related to death.
      In this series, most of the women were illiterate Hindu housewives hailing from
      joint families (i.e. multigenerational groups of related individuals living under
      a single roof) of rural community. The majority (60%) of the affected wives were
      16-25 years of age at the time of the accident and sustained less than 90% total
      body surface area burn injury. Most had the survival period more than 1 day, and
      more than half of them died of septicaemia.

PMID- 14568774
TI  - The gene expression of cytokines and chemokines induced by tourniquet shock in
      mice.
AB  - Traumatic shock is one of the major fields in forensic pathology, but its
      mechanism remains elusive from the pathophysiological aspects. Tourniquet shock
      has been established as one of the animal models of traumatic shock, and we
      examined the gene expression of cytokines and chemokines in the lung and liver in
      tourniquet shock using mice. Tourniquet was conducted by the application of
      elastic bands with five turns at both the thighs as high as possible for 2 h,
      followed by reperfusion. In this procedure, more than 90% mice died within 48 h
      after reperfusion. Serum hepatic transaminase and hematocrit values significantly
      increased at 2 h after reperfusion, and their elevation was still evident after
      10 h. Histopathologically, hemorrhages, congestion and leukocyte recruitment were
      observed in the lung and liver specimens after 6 h of reperfusion.
      Immunohistochemical analysis with anti-myeloperoxidase antibody demonstrated a
      massive neutrophil infiltration in the lung and liver at 2 h or more after
      reperfusion. RT-PCR analyses demonstrated that the gene expression of interleukin
      1beta, tumor necrosis factor-alpha, monocytes chemoattractant protein-1,
      macrophage inflammatory protein (MIP)-1alpha, MIP-2, KC and vascular endothelial
      adhesion molecule-1 was most enhanced in the lung and liver at 2 h after
      reperfusion. Thus, the gene expression of cytokines and chemokines is presumed to
      be closely related with the onset of tourniquet shock. From the forensic aspects,
      these cytokines and chemokines are considered to be useful markers for the early
      diagnosis of tourniquet shock.

PMID- 14568775
TI  - Facial image identification using Photomodeler.
AB  - We present the results of a preliminary study on the use of 3-D software
      (Photomodeler) for identification purposes. Perpetrators may be photographed or
      filmed by surveillance systems. The police may wish to have these images compared
      to photographs of suspects. The surveillance imagery will often consist of many
      images of the same person taken from different angles. We wanted to see if it was
      possible to combine such a suite of images in useful 3-D renderings of facial
      proportions.Fifteen male adults were photographed from four different angles.
      Based on these photographs, a 3-D wireframe model was produced by Photomodeler.
      The wireframe models were then rotated to full lateral and frontal views, and
      compared to like sets of photographs of the subjects. In blind trials, 9/15 of
      the wireframe models were assigned to the correct sets of photographs. In five/15
      cases, the wireframe models were assigned to several sets, including the correct
      set. Only in one case was a wireframe model not assigned to a correct set of
      photographs at all.

PMID- 14568776
TI  - Sequence analysis of two de novo mutation alleles at the DXS10011 locus.
AB  - We have detected two unusual alleles at the DXS10011 locus in two paternity trio
      cases. In one case, one allele of the daughter was found not to have been derived
      from the mother but the other allele was shared with the father. In the other
      case, the mother and the son shared no bands. Paternity in both cases was
      established using conventional polymorphic markers in addition to DNA markers
      (probabilities: >0.999999). Sequencing showed that the two de novo alleles of the
      children acquired a single unit (GAAA).

PMID- 14568777
TI  - A case of acute gasoline intoxication at the scene of washing a petrol tank.
AB  - We encountered a case of acute gasoline intoxication at the scene of washing the
      inner wall of a petrol tank. The decedent was a 50-year-old male, who was the
      supervisor. Two young workers wearing mask respirators began to wash the inner
      wall of the gasoline tank under poor ventilation. About 1 h later, because one of
      the workers lost consciousness, the supervisor entered the tank, without a mask
      respirator, to rescue the worker. However, the supervisor immediately fainted,
      and died 26 h after the accident. In the autopsy, blisters were observed on the
      skin of the face, neck, anterior chest, upper extremities, and back. The heart
      contained hemolyzed blood. Histologically, hemorrhagic pulmonary edema,
      pneumonia, and proximal tubular necrosis were found. In the toxicological
      analyzes, toluene, xylene, and trimethylbenzene were detected in the blood,
      brain, and gastric contents. Toluene concentrations in the blood and brain were
      0.3 mug/ml and 3.7 mug/g, respectively. Since pathological findings were
      consistent with the reported findings concerning gasoline intoxication, and
      constituents of gasoline were in the body, death was attributed to acute gasoline
      intoxication. It was considered that sufficient ventilation and proper use of a
      mask respirator were essential for this kind of work.

PMID- 14568778
TI  - An autopsy case of bilateral tension pneumothorax after acupuncture.
AB  - Acupuncture is one of the most popular complementary therapies in the world.
      Pneumothorax due to perforation of the lungs by needle insertion is one of the
      most common and serious complications of acupuncture treatment. Although there
      have been several case studies of pneumothorax induced by acupuncture, as far as
      we know there have been no reports on the pathological findings of autopsy cases.
      In this report, we describe the pathological findings of an autopsy case of
      bilateral tension pneumothorax after acupuncture. The patient suffered dyspnea
      and chest pain soon the completion of an acupuncture treatment, and died 90 min
      later. Several ecchymoses were macroscopically observed on the parietal pleura in
      the left and right thoracic cavity, suggesting that needles were inserted into
      the thoracic cavity and that the lungs were perforated. The many black spots we
      observed on the parietal pleura along the vertebral column microscopically
      consisted of a number of dust-like black pigments and macrophages containing
      these pigments. These spots seemed to have appeared because of the previous
      insertion of needles.

PMID- 14568779
TI  - Sexual asphyxia by hanging--a case report and a review of the literature.
AB  - A case of sexual asphyxial death by hanging is presented. A 35-year-old male,
      found dead lying on his face in a bed of a truck cab, had hanged himself from a
      window frame using a leather belt. He was completely naked. There were
      pornographic and sadomasochistic magazines beneath his face, opened to pages
      depicted nude photographs of a woman. Autopsy findings revealed a ligature mark
      on the neck and petechial hemorrhages in the conjunctivae, but there were no
      hemorrhages in the neck muscles or fractures of the hyoid bone or the thyroid
      cartilage. The alcohol levels in the blood and urine were 0.78 and 0.45 mg/ml,
      respectively. The circumstances suggested that his death was accidental, and due
      to asphyxia by hanging performed to enhance sexual gratification during
      masturbation. Sexual asphyxia is reviewed and discussed.

PMID- 14568780
TI  - Fatal intussusception in infancy: an experience in forensic autopsy.
AB  - Intussusception, although a common cause of pediatric surgical emergencies, is a
      rarely fatal condition. A 7-month-old infant who was discovered in her cot was
      unresponsive and pronounced dead after 2 h of uneventful cardiopulmonary
      resuscitation in an emergency hospital. Forensic autopsy which was performed in
      order to clarify the circumstances surrounding the death revealed
      intussusceptions at two sites of the ileum. Although morbidity and mortality
      rates from the condition have progressively declined in recent decades but
      avoidable deaths still occur as was experienced in the present case. The forensic
      pathology significance in this case was the occurrence of 'painless
      intussusception' whereby the affected child clinically exhibited no discomfort or
      characteristic features of acute abdomen until death. In summary, the present
      case has exhibited an uncommon fatal occurrence and demonstrated the importance
      of forensic autopsy in such unexpected sudden infant deaths.

PMID- 14568781
TI  - Death creates a bizarre scenery: a case report.
AB  - The bodies of two men in their early forties were found lying in a peculiar
      position in an apartment. Police and medical investigations suggested that both
      had, at the most, died 2 weeks earlier. One of the men was kneeling, holding on
      to the back of a chair-with his hand, and was bent over the second man lying on
      the floor. Both men were known as former addicts, but were assumed to be clean
      for a long period of time. The autopsy revealed that the two men died from an
      acute heroine intoxication in combination with alcohol. The man who lay on the
      floor additionally had chronic heart disease. It could be excluded that any other
      persons were involved in this case and that other causes of death had to be
      considered. The peculiar scene could be explained by the obvious order of death
      and as a consequence of mummification.

PMID- 14568784
TI  - The 5-year incidence and progression of hearing loss: the epidemiology of hearing
      loss study.
AB  - CONTEXT: Hearing impairment affects many older adults, but the incidence is
      unknown. OBJECTIVE: To determine the 5-year incidence and progression of hearing
      impairment. DESIGN: A longitudinal, population-based study of adults aged 48 to
      92 years at baseline examination. Hearing sensitivity was measured twice, 5 years
      apart. SETTING: Testing was conducted at the Beaver Dam Community Hospital,
      Beaver Dam, Wis. PARTICIPANTS: A total of 1636 participants without hearing loss
      and 1085 participants with hearing loss at the baseline examination in 1993-1995
      were reexamined in 1998-2000. MAIN OUTCOME MEASURES: The examinations included
      otoscopy, screening tympanometry, and tone air- and bone-conduction audiometry.
      Incidence of hearing impairment was defined as a pure-tone average (PTA) of
      thresholds at 500, 1000, 2000, and 4000 Hz (PTA 0.5, 1, 2, and 4 kHz) greater
      than 25 dB HL (hearing level) in either ear at follow-up among those without
      hearing loss at baseline. Progression was defined as a change of more than 5 dB
      in the PTA 0.5, 1, 2, and 4 kHz among those with hearing loss at baseline.
      RESULTS: The 5-year incidence of hearing impairment was 21%. More than half of
      those with hearing loss at baseline experienced a decline in hearing. Age was an
      important risk factor for both incidence and progression. Male sex, occupation,
      and education were associated with the incidence of hearing loss after adjusting
      for age. CONCLUSIONS: Older adults have a high risk of developing hearing loss.
      Among those with hearing loss, most experience further declines in hearing
      sensitivity over time. These data indicate that hearing impairment is an
      important public health problem and underscore the need for appropriate hearing
      screening and treatment.

PMID- 14568785
TI  - Community-acquired methicillin-resistant Staphylococcus aureus in children and
      adolescents: changing trends.
AB  - OBJECTIVE: To identify current trends in antibiotic sensitivity patterns of
      community-acquired methicillin-resistant Staphylococcus aureus (CA MRSA)
      infections of the head and neck in children and adolescents and evaluate outcomes
      after therapy. DESIGN: Retrospective review of cases consisting of a medical
      record review with telephone follow-up. SETTING: Two tertiary university medical
      referral centers. PATIENTS: Pediatric patients (age <18 years). MAIN OUTCOME
      MEASURES: Number of cases, sensitivities of cultured organisms, treatments used,
      and outcome of treatments. RESULTS: Seven patients were identified with CA MRSA
      in a 4-month period. Superficial abscesses (3 patients [43%]) and suppurative
      lymphadenitis (3 patients [43%]) were the most common causes. An erythromycin
      resistant, clindamycin-sensitive pattern was observed in 6 (86%) of the 7
      isolates. All infections resolved with prescribed treatments; there were no
      complications. CONCLUSIONS: A high prevalence of erythromycin-resistant,
      clindamycin-sensitive CA MRSA was noted. This new resistance pattern is
      indicative of inducible macrolide-lincomycin-streptogramin-B resistance. Basic
      science data suggest that these strains of bacteria could develop resistance to
      clindamycin during therapy despite appearing susceptible on initial laboratory
      testing. In our small series, clindamycin was used alone and effectively in 2
      such cases. This appears to support its continued use as initial, empiric therapy
      in suspected cases of CA MRSA.

PMID- 14568786
TI  - Myringoplasty: is it worth performing in children?
AB  - OBJECTIVE: To evaluate the results of myringoplasty in children 4 to 14 years old
      at the time of surgery. DESIGN: Retrospective analysis of case notes for 100
      consecutive children who had myringoplasty in a teaching hospital serving as a
      primary care and referral center. METHODS: Between March 1994 and March 1999,
      patients 14 years or younger at the time of surgery were identified by the
      computer database. There were 118 procedures performed in 100 patients (18 had a
      second procedure performed in the contralateral ear at a later date). Twenty
      three patients were excluded because they underwent concurrent mastoid
      exploration, and 6 others because of inadequate follow-up, leaving 89 cases for
      analysis. Data from revision procedures were not included. MAIN OUTCOME MEASURES:
      Graft success was defined as an intact eardrum at 12 months postoperatively and
      middle ear effusion signaled graft failure. Success in terms of hearing was
      defined as an improvement in perception of pure-tone thresholds of 10 dB or
      greater over 2 consecutive frequencies compared with the results of the
      preoperative audiogram. RESULTS: Closure of perforation was achieved in 90% (80)
      of patients, but dropped to 88% (78) as 2 patients developed glue ear. Hearing
      improved in 64 patients (72%), deteriorated in 7 (8%), and remained unchanged in
      18 (20%). There was no case of profound hearing loss. CONCLUSIONS: The success
      rate of myringoplasty in children is comparable to that reported for adults. The
      incidence of middle ear effusion in grafted ears is not higher than that reported
      for nongrafted ears, and children who have had myringoplasty can be treated as
      safely with ventilation tubes as any other children.

PMID- 14568787
TI  - The effect of otitis media with effusion on perceptual masking.
AB  - OBJECTIVE: To determine the effect of otitis media with effusion (OME) on
      perceptual masking (a phenomenon in which spondee threshold for a 2-talker masker
      is poorer than for a speech-shaped noise masker). DESIGN: Longitudinal testing
      over a 1-year period following insertion of tympanostomy tubes, using clinical
      and normal-hearing control groups. SUBJECTS: Forty-seven children having a
      history of OME were tested. Possible testing intervals were just before the
      placement of tympanostomy tubes, and up to 3 separate occasions after the
      placement of the tubes. An age-matched control group of 19 children was tested.
      METHODS: A perceptual masking paradigm was used to measure the ability of the
      listener to recognize a spondee in either a speech-shaped noise or a 2-talker
      masker background. The masker was either continuous or gated on and off with the
      target spondee. RESULTS: In gated masking conditions, children with a history of
      normal hearing showed only slight perceptual masking, but the children with a
      history of OME showed relatively great perceptual masking before surgery and up
      to 6 months following surgery. In continuous masking conditions, both groups of
      children showed relatively great perceptual masking and did not differ
      significantly from each other in this respect either before or after surgery.
      However, before surgery, the OME group showed higher thresholds in both the 2
      talker and speech-shaped noise maskers. CONCLUSIONS: In agreement with previous
      psychoacoustical findings, the relatively great perceptual masking in gated
      conditions shown by children with OME history may reflect a general deficit in
      complex auditory processing.

PMID- 14568788
TI  - The impact of pediatric tracheotomy on parental caregiver burden and health
      status.
AB  - OBJECTIVE: To explore the effects of the placement of a pediatric tracheotomy
      tube on the degree of caregiver burden and overall health status of parents using
      general and disease-specific instruments. METHODS: Between January and July 2001,
      the Medical Outcomes Study Short Form 12 (SF-12) and the Pediatric Tracheotomy
      Health Status Instrument (PTHSI) were administered to 154 families of children
      requiring tracheotomy. Summary scores were generated for each of the 2 scales of
      the SF-12 (the Physical Component Score [PCS] and the Mental Component Score
      [MCS]) as well as for the 4 previously established domains of the PTHSI: domain
      1, physical symptoms of the child (7 items); domain 2, medical visits and cost (7
      items); domain 3, parental rating of the child's psychological health status (3
      items); and domain 4, parental rating of their own caregiver burden (17 items).
      Correlations between responses from the individual domains and between domain 4
      of the PTHSI (reflecting caregiver burden) and the SF-12 were performed. RESULTS:
      The mean +/- SD summary scores for the 4 domains of the PTHSI were domain 1, 22.7
      +/- 5.3; domain 2, 24.9 +/- 6.2; domain 3, 10.5 +/- 4.4; and domain 4, 48.3 +/-
      9.5 (lower scores reflect "poorer" health status). The mean +/- SD summary scores
      of PCS and MCS were 50.5 +/- 11.3 and 35.8 +/- 11.4, respectively. There existed
      a significant correlation between parental caregiver burden (as expressed by
      domain 4) and the child's physical health status (domain 1) (0.32; P<.001) as
      well as between parental caregiver burden and increasing economic costs
      associated with this care (0.27; P<.001). A strong correlation was found between
      the domain measuring parental caregiver burden (domain 4) and the MCS-12 (r =
      0.43; P<.001), while a poor correlation existed with the PCS-12 (r = -0.17; P
      =.14). Nevertheless, in contrast to caregiver burden, the health status of the
      caregivers as measured by the SF-12 did not alter according to the severity of
      illness for the children (P =.17). CONCLUSIONS: Parents caring for children with
      tracheotomy tubes experience significant caregiver burden. These parents appear
      to experience increased burden with respect to the child's severity of illness
      and increased costs associated with caring for their children. Overall, the
      mental health status for an adult caring for a child with a tracheotomy tube is
      significantly reduced and appears to be more affected than physical health
      status.

PMID- 14568789
TI  - Professional diversity and personal commitments of pediatric otolaryngologists.
AB  - OBJECTIVE: To characterize the time demands and practice patterns of pediatric
      otolaryngologists. DESIGN: Prospective survey of members from the American
      Society of Pediatric Otolaryngology. RESULTS: The survey response rate was 54% (n
      = 136) of practicing members of the American Society of Pediatric Otolaryngology.
      Respondents described being actively engaged in clinical otolaryngology (99%),
      hospital or practice administration (71%), private enterprise (17%), research
      (71%), and teaching (89%) on a weekly basis. Sixty percent considered their time
      demands to be "too busy"; however, few anticipated changing their activities in 5
      years. Among the responding physicians, 90% believed that nonotolaryngology peers
      within their institutions viewed pediatric otolaryngology favorably whereas only
      50% thought that other otolaryngologists held the same opinion. CONCLUSIONS:
      Pediatric otolaryngologists participate in many activities beyond clinical
      medicine. While most considered their time demands to be too busy, few
      anticipated a change in their activities. This may be reflective of a high level
      of job satisfaction, financial constraints, or the relative youth of the
      subspecialty.

PMID- 14568790
TI  - Failures and complications of supraglottoplasty in children.
AB  - OBJECTIVES: To study the failures and complications of bilateral
      supraglottoplasty in children with severe laryngomalacia and to compare children
      with isolated laryngomalacia (IL) with those who have additional congenital
      anomalies (ACAs). DESIGN: Retrospective medical record review. SETTING: Two
      tertiary referral centers. SUBJECTS: A total of 136 consecutive patients, aged 3
      days to 60 months (median age, 3 months) who underwent laser or instrumental
      bilateral supraglottoplasty. Isolated laryngomalacia occurred in 102 children,
      aged 3 days to 19 months; ACAs were found in 34 children, aged 3 weeks to 60
      months. OUTCOME MEASURES: Persistence of dyspnea, sleep apnea, and/or failure to
      thrive; need for further treatment; minor complications (defined as granuloma,
      edema, or small web); or major complication (supraglottic stenosis). RESULTS:
      Failures or partial improvement were observed in 12 (8.8%) of 136 cases, all
      having ACAs. The overall rate of complications was 7.4% (10/136). There were no
      significant differences between the IL and ACA groups concerning the rate of
      recurrence needing revision surgery (3/102, 2.9% vs 3/34, 9%), the rate of minor
      complications (4/102, 3.9% vs 1/34, 3%), or the rate of supraglottic stenosis
      (4/102, 3.9% vs 1/34, 3%). Supraglottic stenosis was managed by revision surgery
      in 4 cases and/or noninvasive ventilatory assistance in 2 cases. The long-term
      outcome appeared to be better when reintervention could be avoided or was kept to
      a minimum. CONCLUSION: Failure of supraglottoplasty was only observed in cases of
      laryngomalacia with ACAs. The complication rate was similar whether or not ACAs
      were present.

PMID- 14568791
TI  - A scheduled protocol for the treatment of juvenile recurrent respiratory
      papillomatosis with intralesional cidofovir.
AB  - OBJECTIVE: To assess the efficacy of treating juvenile recurrent respiratory
      papillomas with intralesional cidofovir using a scheduled treatment protocol.
      DESIGN: Prospective case series. SETTING: Tertiary care academic medical center.
      PATIENTS: Of 5 pediatric patients with recurrent respiratory papillomas, 2 had
      severe recurrent papillomatosis requiring long-term therapy of laser ablations
      every 2 weeks prior to cidofovir treatments. The 3 other patients were newly
      diagnosed or had milder disease. INTERVENTION: Intralesional cidofovir (1 mg/kg)
      was administered during each scheduled visit. The first 4 treatments were at 2
      week intervals (week 0, 2, 4, and 6). Subsequent treatment intervals were each
      increased by 1 week (treatments took place at week 9, 13, 18, 24, etc).
      Concomitant laser ablation was used only for bulky lesions. MAIN OUTCOME
      MEASURES: Papilloma stage and need for laser ablation at each scheduled visit.
      RESULTS: The mean follow-up time was 66 weeks. The mean (SD) papilloma stage
      decreased from 9.2 (5.5) at initial presentation to 3.4 (2.6) within 2 weeks of
      the first injection (P<.05), and continued to decrease for the remaining of the
      follow-up period. Papilloma stage 0 was achieved in 4 of the 5 patients. The need
      for laser ablation of papillomas also decreased within 4 weeks of treatment
      initiation (P<.05). At 9 weeks, no patient required laser therapy. One patient
      was removed from the protocol after 58 weeks. CONCLUSION: An intralesional
      treatment protocol with cidofovir and increasing intervals between scheduled
      treatment was successful the long-term management of juvenile respiratory
      papillomatosis.

PMID- 14568792
TI  - Postoperative hemorrhage with nonsteroidal anti-inflammatory drug use after
      tonsillectomy: a meta-analysis.
AB  - OBJECTIVE: To use standard meta-analysis techniques to determine the risk of
      postoperative hemorrhage associated with the use of nonsteroidal anti
      inflammatory drugs (NSAIDs) after tonsillectomy. DATA SOURCES: The MEDLINE
      database (1966-2001) restricted to the English language was searched using the
      keywords tonsillectomy, hemorrhage, analgesics, and NSAID in various
      combinations. Additionally, published articles were cross-referenced. To ensure
      completeness, the search was rerun using the Science Citation Index database.
      STUDY SELECTION: Of the 110 articles identified, 7 were selected. Selected
      studies were prospective trials comparing the effects of an NSAID and a control
      drug on posttonsillectomy pain and hemorrhage in pediatric and/or adult patients.
      In all cases, the NSAID or control was administered through an enteric route in
      the postoperative period. Patients were monitored for early and delayed
      hemorrhage. DATA EXTRACTION: Data were extracted independently by 2
      investigators. DATA SYNTHESIS: A random effects model was used to compute a
      pooled odds ratio. For the 1368 patients included in analysis, the pooled odds
      ratio of posttonsillectomy hemorrhage with NSAIDs compared with controls was 1.29
      and was not statistically significant (95% confidence interval, 0.85-1.73;
      P>/=.05). A subgroup analysis revealed an odds ratio of 0.93 (95% confidence
      interval, 0.44 -1.95; P>/=.05) for the nonaspirin NSAID group, while the aspirin
      group had a statistically significant odds ratio of 1.94 (95% confidence
      interval, 1.09-3.42; P =.02). CONCLUSIONS: There is an increased risk of
      posttonsillectomy hemorrhage with the use of aspirin after tonsillectomy;
      however, there appears to be no significant increased risk of bleeding for
      nonaspirin NSAIDs in this meta-analysis.

PMID- 14568793
TI  - Establishing normative voice-related quality of life scores within the pediatric
      otolaryngology population.
AB  - OBJECTIVE: To establish normative values for voice-related quality of life across
      a broad pediatric otolaryngology population using the Pediatric Voice Outcome
      Survey (PVOS). DESIGN: Longitudinal study. SETTING: Multiphysician outpatient
      pediatric otolaryngology practice. METHODS: The PVOS was completed by 385 parents
      of children and adolescents aged 2 to 18 years. Of the 385 parents, 75 were
      readministered the instrument 2 weeks after no intervention had been provided.
      Data were collected regarding the patients' age, main diagnosis, and operative
      intervention. RESULTS: The PVOS demonstrated robust internal consistency with an
      overall Cronbach alpha value of.70. Test-retest reliability demonstrated a
      weighted kappa value of 0.89 (95% confidence interval, 0.84-0.95) The mean +/- SD
      converted score (based on a 0-100 scale) for the overall population was 80.5 +/-
      19.9. Converted PVOS scores are provided for each subpopulation according to main
      diagnosis. The PVOS scores varied significantly according to age (P<.05) and
      preoperative and postoperative status following adenoidectomy (P<.05).
      CONCLUSION: The PVOS represents a valid and reliable instrument to measure voice
      related quality of life in a broad pediatric otolaryngology population.

PMID- 14568794
TI  - The role of Chlamydia pneumoniae infection in children with chronic sinusitis.
AB  - BACKGROUND: Chlamydia pneumoniae infection is a frequent cause of lower
      respiratory disease in both adults and children. However, its role in upper
      respiratory disease, including sinusitis, is less clear. OBJECTIVE: To determine
      the role of infection with C. pneumoniae in chronic sinusitis in children.
      DESIGN: Prospective collection of specimens. SETTING: Tertiary care academic
      medical center. PARTICIPANTS: Children with clinical and radiologic evidence of
      chronic sinusitis unresponsive to medical management undergoing adenoidectomy,
      maxillary sinus lavage, or endoscopic sinus surgery for treatment. Intervention
      Nasopharyngeal and middle meatal swabs and portions of surgical specimens were
      obtained and cultured for C. pneumoniae. RESULTS: Specimens were obtained from 20
      children (14 boys and 6 girls) aged 3 through 16 years. Thirteen bilateral
      endoscopic ethmoidectomies with maxillary antrostomies, 10 adenoidectomies, and 3
      bilateral maxillary sinus lavages were performed. Chlamydia pneumoniae was
      isolated from the nasopharyngeal swab and adenoid tissue of 1 child (aged 6
      years); however, his middle meatal swabs and maxillary sinus aspirates were
      negative. After 10 days of treatment with clarithromycin, repeat nasopharyngeal
      cultures were negative for C. pneumoniae. CONCLUSIONS: With the use of sensitive
      culture methods, C. pneumoniae was not isolated from sinus specimens of children
      enrolled in this study. This preliminary study suggests that C. pneumoniae does
      not play a significant role in chronic sinusitis in children.

PMID- 14568796
TI  - Surgical treatment of cervical nodal metastases in patients with papillary
      thyroid carcinoma.
AB  - OBJECTIVE: To determine if more extensive neck dissection in patients with
      papillary carcinoma of the thyroid affords a survival benefit vs limited
      lymphadenectomy of positive nodal disease. DESIGN: Survey analysis of a national
      cancer database. METHODS: Cases of papillary thyroid carcinoma were extracted
      from the Surveillance, Epidemiology, and End Results database for January 1,
      1988, to December 31, 1999, along with demographic, staging, and treatment
      variables. Cases were limited to patients who underwent total thyroidectomy and
      postoperative radioactive iodine treatment along with excision of 1 or more
      positive cervical nodes. Patients were divided into 2 groups: those undergoing
      limited lymphadenectomy of only positive nodes and those undergoing more
      extensive neck dissection with removal of positive and negative nodes. RESULTS:
      Among 2097 patients with papillary carcinoma meeting treatment criteria, 880
      underwent limited lymphadenectomy and 1217 underwent neck dissection. The mean
      age, sex distribution, primary tumor extent and size, and follow-up duration were
      not different between these 2 groups (P>.05 for all). The mean survival for
      patients undergoing limited lymphadenectomy was 135 months, vs 136 months for
      patients undergoing neck dissection. Actuarial 5-year (10-year) survival rates
      were 94.4% (91.3%) and 95.9% (92.4%), respectively. Kaplan-Meier survival was not
      different between groups (P =.40, log-rank test). CONCLUSIONS: Limited
      lymphadenectomy of positive nodal disease in patients with papillary carcinoma
      affords survival similar to that of patients undergoing more extensive neck
      dissections. Therefore, a formal neck dissection may not be required for the
      effective treatment of cervical nodal metastases in patients with papillary
      carcinoma of the thyroid.

PMID- 14568795
TI  - Evaluation of topical povidone-iodine in chronic suppurative otitis media.
AB  - OBJECTIVES: To evaluate if povidone-iodine (PVP-I) can be used topically in the
      treatment of chronic suppurative otitis media-tubotympanic disease and to compare
      it with ciprofloxacin hydrochloride ear drops. DESIGN: Prospective double-blind
      randomized study. SETTING: Academic tertiary medical center. PATIENTS: Forty
      patients with chronic suppurative otitis media were randomized into 2 groups.
      INTERVENTION: One group (19 patients) received 5% PVP-I ear drops, while the
      other group (21 patients) received 0.3% ciprofloxacin ear drops. Both were
      administered topically, 3 drops 3 times daily for 10 days. These patients were
      followed up at weekly intervals for up to 4 weeks after commencing therapy.
      RESULTS: Clinical improvement at the end of study was 88% in the PVP-I group and
      90% in the ciprofloxacin group. The most commonly isolated organism was
      Pseudomonas aeruginosa. In vitro resistance to ciprofloxacin was seen in 17% of
      organisms, while no resistance was seen for PVP-I. CONCLUSIONS: To our knowledge,
      this is the first study to evaluate the efficacy of PVP-I as a topical agent in
      the treatment of chronic suppurative otitis media. The results show that
      clinically, topical PVP-I is as effective as topical ciprofloxacin, with a
      superior advantage of having no in vitro drug resistance. Also, there is an added
      benefit of reduced cost of therapy.

PMID- 14568797
TI  - Feasibility and cost-effectiveness of sentinel lymph node radiolocalization in
      stage N0 head and neck cancer.
AB  - OBJECTIVES: To determine the feasibility of sentinal lymph node (SN)
      radiolocalization and to assess the cost-effectiveness of the SN navigation
      surgery strategy in patients with stage N0 squamous cell carcinoma (SCC) of the
      head and neck. Patients Eleven consecutive patients with stage N0 SCC of the head
      and neck. METHODS: Head and neck lymphoscintigraphy was performed 2 hours after
      the injection of technetium Tc 99m tin colloid or phytate. A handheld gamma probe
      was used to detect the SN before and directly after making a skin incision. Nodes
      were evaluated histopathologically for micrometastasis. To determine the expected
      cost savings, a decision tree sensitivity analysis was designed based on the 2
      competing strategies: ipsilateral neck dissection vs SN navigation surgery. The
      costs referred to billed costs based on the Japanese national insurance
      reimbursement system. RESULTS: The sensitivity of SN navigation surgery in our
      series was 100% (11/11) on a patient-by-patient basis and 94% (17/18) on a node
      by-node basis. Micrometastasis was found in 36% (4/11). Assuming the
      micrometastasis prevalence, sensitivity, and specificity of navigation surgery
      for detecting SN to be 30%, 90%, and 100%, respectively, the decision tree
      sensitivity analysis showed that introduction of SN navigation surgery in place
      of ipsilateral neck dissection would yield cost savings of $1218 (US) per stage
      N0 patient in Japan and avoid 7 surgical deaths per 1000 patients who are
      supposed to undergo neck dissection in the neck dissection strategy. Break-even
      point analysis for the SN navigation surgery strategy showed that the threshold
      value required more than 41 patients for the savings to begin to accrue.
      CONCLUSION: Our results indicate that SN navigation surgery using
      radiolocalization is feasible and cost-effective, based on decision tree
      sensitivity analysis, in patients with stage N0 SCC of the head and neck.

PMID- 14568798
TI  - Angiogenesis and the expression of vascular endothelial growth factors A and C in
      squamous cell carcinoma of the piriform fossa.
AB  - BACKGROUND: Angiogenesis is essential for tumor growth and invasion. Vascular
      endothelial growth factor A (VEGF-A) is a prime mediator of tumor angiogenesis;
      VEGF-C, another member of the closely related VEGF family of proteins, has major
      effects on lymphatic endothelial cells and may be important in the process of
      lymphatic metastasis. OBJECTIVES: To evaluate the expression of these cytokines
      in hypopharyngeal squamous cell carcinoma and to ascertain the effects of these
      proteins on lymphatic metastasis and vascular angiogenesis. DESIGN: Retrospective
      analysis of microvessel density and the expression of VEGF-A and VEGF-C. SETTING:
      An academic referral center. Subjects Thirty-four patients with stage T2 to T4
      squamous cell carcinoma of the piriform fossa. INTERVENTIONS: Expression of VEGF
      A and VEGF-C was determined by immunohistochemistry on formalin-fixed, paraffin
      embedded biopsy specimens. Angiogenesis was measured as microvessel density by
      staining endothelial cells for platelet-endothelial cell adhesion molecule
      1/CD31. RESULTS: Of the 34 tumors, 21 had clinicoradiologic evidence of lymphatic
      metastasis. Expression of VEGF-C was associated with lymphatic metastasis
      (P<.001), but not with microvessel density. The VEGF-A expression correlated with
      microvessel density (P<.001), but neither VEGF-A expression nor microvessel
      density was associated with lymphatic metastasis. CONCLUSIONS: The expression of
      VEGF-C is associated with lymphatic metastasis in squamous cell carcinoma of the
      piriform fossa. This is not secondary to effects on vascular angiogenesis and is
      hypothesized to be due to effects on lymphatic endothelial cells.

PMID- 14568799
TI  - Epstein-Barr virus detected in a head and neck squamous cell carcinoma cell line
      derived from an immunocompromised patient.
AB  - BACKGROUND: DNA tumor viruses potentially play a role in the development of
      squamous cell carcinoma of the head and neck (SCCHN). Human papillomavirus is
      found in up to 50% of SCCHN specimens, and Epstein-Barr virus (EBV) has been
      detected in nasopharyngeal carcinoma, Burkitt lymphoma, and other lymphomas.
      However, the role of EBV in nonnasopharyngeal SCCHN has not been thoroughly
      investigated. METHODS: Twenty-one SCCHN cell lines derived from tumors of various
      subsites were used to screen for EBV DNA as well as latent viral protein
      expression. The method of EBV DNA detection was polymerase chain reaction with 3
      independent primer sets from distinct regions of the genome. Expression of the
      viral protein EBNA-1, critical for the maintenance of the viral episome, was
      monitored by immunofluorescence using an antibody specific for EBNA-1. In
      addition, 12 paraffin-embedded tumor specimens and adjacent normal tissues were
      analyzed by polymerase chain reaction. These tumor specimens were further
      characterized by immunohistochemistry with the use of a mouse monoclonal antibody
      that recognizes EBNA-1. RESULTS: Little or no EBV DNA was detected in 20 of 21
      cell lines or in any of the tumor specimens, while detecting approximately 40
      genome copies in a control reaction. Accordingly, these cell lines and specimens
      were negative for EBNA-1 expression. In 1 cell line derived from an
      immunosuppressed patient, EBV DNA was detected, and on further examination a
      small percentage of cells expressed EBNA-1 as shown by immunofluorescence.
      CONCLUSIONS: Although EBV may not be a major cofactor contributing to the
      proliferation of SCCHN, the limited initial evidence suggests that EBV may be
      involved in development of SCCHN in immunosuppressed patients.

PMID- 14568801
TI  - Progressive stapedial fixation in Beckwith-Wiedemann syndrome.
AB  - Beckwith-Wiedemann syndrome is a genetic fetal overgrowth disturbance
      characterized by organomegaly, abdominal wall defects, postnatal hypoglycemia,
      and increased frequency of embryonic and postnatal tumors. Hearing loss in
      connection with this syndrome is rare. We describe a patient with Beckwith
      Wiedemann syndrome having a progressive conductive hearing loss caused by a
      stapedial footplate fixation occurring during preschool age. We studied
      progression of the hearing impairment audiometrically from the patient's fourth
      year of life until age 19. In the right ear, it progressed from a mean pure-tone
      hearing level of 10 dB to 70 dB, with a perceptive component of 30 dB. The
      hearing level of the left ear remained at 25 dB. An exploratory tympanotomy
      disclosed stapedial fixation, and a partial stapedectomy improved the hearing
      level in the right ear to 30 to 35 dB. In patients with Beckwith-Wiedemann
      syndrome, a progressive conductive hearing loss, caused by stapedial footplate
      fixation, may develop after birth. Clinically, the fixation is identical to
      otosclerosis, but the typical family history of otosclerosis is lacking.

PMID- 14568800
TI  - Defect repair in the rat mandible with bone morphogenic protein 5 and
      prostaglandin E1.
AB  - OBJECTIVE: To compare the osteogenic abilities of 2 growth factors (bone
      morphogenic protein 5 [BMP-5] and prostaglandin E1 [PGE1]) and 2 carriers
      (collagen/polylactic acid [PLA] and collagen/calcium hydroxyapatite cement [HAC])
      in the repair of a rat mandibular body defect. DESIGN: Prospective controlled
      trial. Subjects Twenty-nine Sprague-Dawley rats. INTERVENTIONS: Critical size
      defects were created in the bilateral mandibular bodies of the rats. Each
      hemimandible was assigned to an experimental group. The defects were filled with
      PLA (group 1), PLA with BMP-5 (group 2), PLA with PGE1 (group 3), HAC (group 4),
      HAC with BMP-5 (group 5), or HAC with PGE1 (group 6). The control group (group 7)
      had unfilled defects. The animals were killed after 12 weeks, and the
      nondemineralized specimens were processed histologically. Stereologic techniques
      were used to determine the volume fractions of new bone, osteoid, marrow,
      remaining implant, and fibrous tissue in each defect. RESULTS: The HAC/BMP-5
      group (group 5) contained significantly more new bone than the PLA/BMP-5 group
      (group 2) (P =.02), the HAC and HAC/PGE1 groups (groups 4 and 6) (P =.002), and
      the control group (group 7) (P<.01). The HAC/BMP-5 group also had less fibrous
      tissue than the HAC group and the HAC/PGE1 group (P<.001). Groups 5 and 6 had
      less fibrous tissue than group 7 (P<.01). The groups containing PGE1 demonstrated
      significantly more osteoid development than the other experimental groups
      (P<.001). CONCLUSIONS: Inclusion of BMP-5 in an implant with calcium
      hydroxyapatite cement resulted in the formation of significantly larger fractions
      of new bone and less fibrous tissue ingrowth than occurred in the other
      experimental groups. The presence of PGE1 resulted in larger amounts of osteoid
      deposition, suggesting the potential for delayed bone healing.

PMID- 14568802
TI  - Pathology quiz case. Nasal T/NK-cell lymphoma.

PMID- 14568803
TI  - Radiology quiz case. Thornwaldt cyst.

PMID- 14568804
TI  - Stroke risk, hypertension, and HRTless postmenopausal therapy.

PMID- 14568805
TI  - The Basal Ganglia and involuntary movements: impaired inhibition of competing
      motor patterns.
AB  - The basal ganglia are organized to facilitate voluntary movements and to inhibit
      competing movements that might interfere with the desired movement. Dysfunction
      of these circuits can lead to movement disorders that are characterized by
      impaired voluntary movement, the presence of involuntary movements, or both.
      Current models of basal ganglia function and dysfunction have played an important
      role in advancing knowledge about the pathophysiology of movement disorders, but
      they have not contained elements sufficiently specific to allow for understanding
      the fundamental differences among different involuntary movements, including
      chorea, dystonia, and tics. A new model is presented here, building on existing
      models and data to encompass hypotheses of the fundamental pathophysiologic
      mechanisms underlying chorea, dystonia, and tics.

PMID- 14568806
TI  - The application of implant technology for cybernetic systems.
AB  - OBJECTIVE: To assess the usefulness, compatibility, and long-term operability of
      a microelectrode array into the median nerve of the left arm of a healthy
      volunteer, including perception of feedback stimulation and operation of an
      instrumented prosthetic hand. SETTING: The study was carried out from March 14
      through June 18, 2002, in England and the United States. RESULTS: The blindfolded
      subject received feedback information, obtained from force and slip sensors on
      the prosthetic hand, and subsequently used the implanted device to control the
      hand by applying an appropriate force to grip an unseen object. Operability was
      also demonstrated remotely via the Internet, with the subject in New York, NY,
      and the prosthetic hand in Reading, England. Finally, the subject was able to
      control an electric wheelchair, via decoded signals from the implant device, to
      select the direction of travel by opening and closing his hand. The implantation
      did not result in infection or any perceivable loss of hand sensation or motion
      control. The implant was finally extracted because of mechanical fatigue of the
      percutaneous connection. Further testing after extraction has not indicated any
      measurable long-term defects in the subject. CONCLUSIONS: This implant may allow
      recipients to have abilities they would otherwise not possess. The response to
      stimulation improved considerably during the trial, suggesting that the subject
      learned to process the incoming information more effectively.

PMID- 14568807
TI  - Increased risk of stroke in hypertensive women using hormone therapy: analyses
      based on the Danish Nurse Study.
AB  - BACKGROUND: Recent randomized clinical trials suggest an increased risk of stroke
      with hormone therapy (HT), whereas observational studies have suggested mixed
      results. Differences in design, definitions of HT exposure, and stroke outcome
      may explain these discrepancies. Little attention has been paid to identifying
      subgroups of women who are particularly sensitive to HT. OBJECTIVES: To
      investigate the risk of various stroke outcomes among women using HT based
      primarily on estradiol-17beta (unopposed or combined with norethisterone acetate)
      and to assess the potential modifying effect by presence of risk factors for
      stroke. DESIGN: Prospective cohort study. SETTING: In 1993, the Danish Nurse
      Study was established, and questionnaires on lifestyle and HT use were sent to
      all Danish nurses older than 44 years, of whom 19,898 (85.8%) replied.
      PARTICIPANTS: Postmenopausal women (n = 13,122) free of previous major
      cardiovascular and cerebrovascular disease and cancer. MAIN OUTCOME MEASURE:
      Ischemic or hemorrhagic stroke (n = 144) identified in the national registries of
      hospital discharges and cause of deaths in the total follow-up through December
      31, 1998. RESULTS: In 1993, 28.0% of the 13 122 were current HT users, 14.3% were
      past users, and 57.7% were never users. Overall, HT exposure was not consistently
      associated with stroke. However, subdivision based on the presence of
      hypertension showed a significantly increased risk of stroke among hypertensive
      women. Compared with hypertensive never HT users, an increased risk of total
      stroke was found with current use (hazard ratio, 2.35; 95% confidence interval,
      1.16-4.74) and especially with current use of estrogen-progestin (hazard ratio,
      3.00; 95% confidence interval, 1.33-6.76). Normotensive women had no increased
      risk of stroke with HT. CONCLUSIONS: We found an increased risk of stroke among
      hypertensive but not normotensive women using HT. The present study suggests that
      HT should be avoided in hypertensive women.

PMID- 14568808
TI  - Prevalence and classification of mild cognitive impairment in the Cardiovascular
      Health Study Cognition Study: part 1.
AB  - OBJECTIVE: To examine the prevalence of mild cognitive impairment (MCI) and its
      diagnostic classification in the Cardiovascular Health Study (CHS) Cognition
      Study. DESIGN: The CHS Cognition Study is an ancillary study of the CHS that was
      conducted to determine the presence of MCI and dementia in the CHS cohort.
      SETTING: Multicenter population study. PATIENTS: We examined 3608 participants in
      the CHS who had undergone detailed neurological, neuropsychological,
      neuroradiological, and psychiatric testing to identify dementia and MCI. MAIN
      OUTCOME MEASURES: The prevalence of MCI was determined for the whole cohort, and
      specific subtypes of MCI were examined in detail only at the Pittsburgh, Pa,
      center (n = 927). Mild cognitive impairment was classified as either MCI amnestic
      type or MCI multiple cognitive deficits-type. RESULTS: The overall prevalence of
      MCI was 19% (465 of 2470 participants); prevalence increased with age from 19% in
      participants younger than 75 years to 29% in those older than 85 years. The
      overall prevalence of MCI at the Pittsburgh center was 22% (130 of 599
      participants); prevalence of the MCI amnesic-type was 6% and of the MCI multiple
      cognitive deficits-type was 16%. CONCLUSIONS: Twenty-two percent of the
      participants aged 75 years or older had MCI. Mild cognitive impairment is a
      heterogeneous syndrome, where the MCI amnestic-type is less frequent than the MCI
      multiple cognitive deficits-type. Most of the participants with MCI had comorbid
      conditions that may affect their cognitive functions.

PMID- 14568809
TI  - Risk factors for mild cognitive impairment in the Cardiovascular Health Study
      Cognition Study: part 2.
AB  - OBJECTIVE: To examine the risk factors for mild cognitive impairment (MCI) in a
      longitudinal population study-the Cardiovascular Health Study Cognition Study.
      DESIGN: We examined the factors that in the period 1991 through 1994 predicted
      the development of MCI in all participants of the Cardiovascular Health Study
      Cognition Study. Further examination was conducted in the Pittsburgh, Pa, cohort
      (n = 927), where participants with MCI were classified as having either the MCI
      amnestic-type or the MCI multiple cognitive deficits-type. SETTING: Multicenter
      population study. PATIENTS: This study includes all participants of the
      Cardiovascular Health Study Cognition Study (n = 3608) who had a magnetic
      resonance imaging (MRI) scan of the brain between 1991 and 1994, and detailed
      neuropsychological, neurological, and medical evaluations to identify the
      presence of MCI or dementia in the period 1998 to 1999. The mean time between the
      closest clinical examination to the MRI and the diagnostic evaluation for
      cognitive disorders was 5.8 years for the Cardiovascular Health Study Cognition
      Study cohort and 6.0 years for the Pittsburgh cohort. MAIN OUTCOME MEASURES: Risk
      factors for MCI at the time of the MRI were identified using logistic regression,
      controlling for age, race, educational level, baseline Modified Mini-Mental State
      Examination and Digit Symbol Test scores, measurements of depression, MRI
      findings (atrophy, ventricular volume, white matter lesions, and infarcts), the
      presence of the apolipoprotein E (APOE) epsilon4 allele, hypertension, diabetes
      mellitus, and heart disease. RESULTS: Mild cognitive impairment (n = 577) was
      associated with race (African American), low educational level, low Modified Mini
      Mental State Examination and Digit Symbol Test scores, cortical atrophy, MRI
      identified infarcts, and measurements of depression. The MCI amnestic-type was
      associated with MRI-identified infarcts, the presence of the APOE epsilon4
      allele, and low Modified Mini-Mental State Examination scores. The MCI multiple
      cognitive deficits-type was associated with low Modified Mini-Mental State
      Examination and Digit Symbol Test scores. CONCLUSIONS: The development of MCI is
      associated with measurements of cognition and depression, racial and
      constitutional factors, and cerebrovascular disease. Early cognitive deficits
      seem to be a common denominator for the 2 forms of MCI; the presence of
      cerebrovascular disease and the APOE epsilon4 allele is associated with the
      amnestic type of MCI.

PMID- 14568810
TI  - Orthostatic hypotension in de novo Parkinson disease.
AB  - BACKGROUND: It is accepted that orthostatic hypotension is a clinical marker for
      the diagnosis of multiple system atrophy, but conflicting data indicate that it
      may also be present in Parkinson disease (PD). OBJECTIVES: To evaluate the
      prevalence of autonomic cardiovascular impairment and orthostatic hypotension in
      a large group of patients with de novo PD, followed up for at least 7 years, to
      clinically confirm the diagnosis of the disease. METHODS: During a 2-year
      recruiting period, 60 untreated patients diagnosed as having idiopathic PD
      underwent autonomic cardiovascular function evaluation using the Ewing test.
      Patients subsequently received dopaminergic therapy and their condition was
      followed up for at least 7 years. RESULTS: Nine (15%) of 60 patients were
      excluded from the study because during the follow-up period a parkinsonian
      syndrome was diagnosed (5 had multiple system atrophy and 4 had progressive
      supranuclear palsy). Data from 51 patients with PD underwent final statistical
      analysis and the results were compared with those of 51 age-matched healthy
      control subjects who had taken the same battery of autonomic tests. A
      statistically significant difference was found in postural hypotension (P =.02)
      and deep breathing test results (P =.03) between patients and controls. Seven
      (14%) of 51 patients with PD and 3 (60%) of 5 patients with multiple system
      atrophy had a decrease of more than 20 mm Hg in systolic blood pressure on
      standing. CONCLUSIONS: Data from this study indicate a high prevalence of
      sympathetic and parasympathetic failure in patients with de novo PD, and when
      using a decrease of at least 20 mm Hg in systolic blood pressure, manometric
      orthostatic hypotension was found in 7 (14%) of the 51 patients with de novo PD.

PMID- 14568811
TI  - Prediction of incident neurocognitive impairment by plasma HIV RNA and CD4 levels
      early after HIV seroconversion.
AB  - BACKGROUND: Neuropsychological (NP) impairment is a relatively common sequela in
      human immunodeficiency virus (HIV)-infected individuals with advanced disease.
      Early antecedents of NP dysfunction, however, remain poorly understood.
      OBJECTIVE: To determine whether early markers of immunocompetence and viral
      replication in individuals who have undergone seroconversion would be of
      prognostic value in identifying subjects who would become cognitively impaired.
      METHODS: Seventy-four subjects with estimable seroconversion dates and normal
      cognition at baseline (a median of 1 year after seroconversion) received NP and
      laboratory evaluations, including reverse transcription-polymerase chain reaction
      measurements of plasma (N = 74) and cerebrospinal fluid (n = 47) levels of HIV
      RNA. Subjects were followed up longitudinally, and were considered to have
      reached the end point if they became cognitively impaired. RESULTS: Using Kaplan
      Meier estimates, the subgroups with the most rapid progression to NP impairment
      were (1) subjects with early reductions in CD4 counts (<400 cells/microL at
      baseline; P =.007) and (2) those with elevated plasma HIV RNA values (>4.5 log10
      copies/mL; P =.03) early after seroconversion. Using proportional hazards
      modeling, the highest-risk subjects had both CD4 counts less than 400
      cells/microL and HIV RNA levels greater than 4.5 log10 copies/mL (risk ratio,
      6.0; P =.01). In most subjects (7/9 [78%]), NP impairment developed before an
      acquired immunodeficiency syndrome-defining illness. CONCLUSIONS: Neurocognitive
      outcomes in HIV are strongly influenced by very early systemic virological and
      immunological events. Patients with high plasma levels of HIV RNA and low CD4
      counts early after infection should be aggressively treated to prevent
      immunological decline and NP deterioration.

PMID- 14568812
TI  - Benign calf amyotrophy: clinicopathologic study of 8 patients.
AB  - BACKGROUND: The benign focal amyotrophy disorders have been described since 1959
      for the upper limbs and since 1981 for the lower limbs. The clinicopathologic
      features have pointed to a restricted and self-limiting form of motor neuron
      disease. OBJECTIVE: To describe the clinical, electromyographic, and muscle
      histopathologic features in 8 patients with benign calf amyotrophy. DESIGN:
      Retrospective review of patient charts, electromyograms, and muscle
      histopathology. PATIENTS AND RESULTS: Eight patients, aged 37 to 88 years,
      developed insidiously progressive calf muscle weakness and wasting during 1 to 5
      years. The gastrocnemius weakness and wasting were bilateral in 4 patients.
      Initial progression of symptoms was followed by disease stabilization. None had a
      history of poliomyelitis or family history of neuromuscular disease. Creatine
      kinase values were mildly elevated in 5 patients. The electromyographic and
      muscle histopathologic findings were consistent with a chronic neuropathic
      disorder. Despite the restricted calf muscle involvement clinically, the
      electromyographic abnormalities suggested more diffuse lower limb involvement.
      Further studies, including DNA tests and muscle-based protein studies, excluded
      several types of inherited neuromuscular disorders. CONCLUSIONS: Benign calf
      amyotrophy is a variant of the benign focal amyotrophy disorders. The etiology
      for these disorders is unknown. Studies to exclude other causes of calf
      amyotrophy and careful follow-up examinations to document disease stabilization
      are necessary to diagnose this uncommon disorder.

PMID- 14568813
TI  - Atypical phenotypes in patients with facioscapulohumeral muscular dystrophy 4q35
      deletion.
AB  - BACKGROUND: Facioscapulohumeral muscular dystrophy (FSHD) is associated with a
      deletion on chromosome 4q35. Recent studies have shown that this deletion is
      found in patients with other phenotypes in addition to those with the classic
      Landouzy-Dejerine FSHD phenotype. OBJECTIVE: To examine patients with atypical
      phenotypes and an FSHD deletion on chromosome 4q35. DESIGN: Clinical
      characterization and genotype-phenotype correlation. SETTING: University
      hospital. PATIENTS: Forty-one symptomatic subjects with deletions on chromosome
      4q35. RESULTS: We found 6 patients with atypical FSHD. Three (from a single
      family with FSHD) had additional symptoms of chronic progressive external
      ophthalmoplegia (4q35 EcoRI/BlnI fragment size, 20 kilobase [kb]), and 3 patients
      (1 with sporadic disease and 2 from a single family) had facial-sparing
      scapulohumeral dystrophy (4q35 EcoRI/BlnI fragment size, 30 and 34 kb,
      respectively). CONCLUSIONS: The clinical presentations in patients with FSHD
      associated short fragments on chromosome 4q35 are not restricted to the classic
      FSHD form, but constitute a variety of clinical manifestations. There seems to be
      no clear correlation between the atypical subtype and the DNA fragment size due
      to the deletion.

PMID- 14568814
TI  - In vivo voxel-based morphometry in multiple system atrophy of the cerebellar
      type.
AB  - BACKGROUND: Multiple system atrophy (MSA) is a sporadic neurodegenerative
      disease. According to the clinical presentation a parkinsonian type and a
      cerebellar type (MSA-C) are distinguished. OBJECTIVE: To study the morphological
      alterations of MSA-C-affected brains in vivo using voxel-based morphometric
      analysis of magnetic resonance images. SETTING: University hospital. PATIENTS:
      Fourteen patients (5 men and 9 women) with MSA-C (mean age [SD], 59.4 [7.4]
      years; mean [SD] disease duration, 3.7 [1.4] years) and 13 healthy control
      subjects (5 men and 8 women) (mean [SD] age, 55.1 [6.9] years) were studied.
      METHODS: T1-weighted magnetic resonance images were normalized to a common
      stereotaxic space and segmented into gray and white matter. Data were analyzed
      using statistical parametric mapping (SPM99). RESULTS: Gray matter was reduced in
      the brainstem and the anterior lobe of the cerebellum. Reduction of white matter
      was observed in the middle cerebellar peduncles, cerebellar white matter, and
      brainstem. The inverted comparison revealed an increase of white matter density
      along the pyramidal tracts. CONCLUSIONS: Voxel-based morphometry revealed a
      significant loss of cerebellar and brainstem tissue in MSA-C. It allowed a
      precise anatomical localization and a distinction between gray and white matter
      densities. In addition, our data point to a particular involvement of the
      pyramidal tract in MSA-C.

PMID- 14568815
TI  - Chronic cognitive impairment following laterothalamic infarcts: a study of 9
      cases.
AB  - BACKGROUND: The occlusion of the lateral thalamic arteries leads to infarcts of
      ventrolateral thalamic nuclei, the ventroposterior nucleus, and the rostrolateral
      part of pulvinar, and produces hemisensory loss with or without hemiataxia.
      Cognitive impairment after such strokes has not been systematically studied.
      OBJECTIVE: To determine the nature and the extent of long-lasting cognitive
      deficits following lateral thalamic strokes. DESIGN: Case series. SETTING:
      Neurology department, Lausanne University Hospital, Lausanne, Switzerland.
      PATIENTS: Nine patients with hemisensory loss due to an isolated laterothalamic
      infarct. MAIN OUTCOME MEASURES: Three to 6 months after stroke onset, standard
      neuropsychologic evaluation, including testing of language, ideomotor and
      constructive praxis, visual gnosis, spatial attention, learning abilities, and
      executive functions. RESULTS: Six of 9 patients showed some degree of cognitive
      impairment. Executive functions tasks, particularly verbal fluency, were impaired
      in 5 patients (4 with right and 1 with left lesion). Learning and delayed recall
      in visuospatial and verbal tasks, but not in recognition, were impaired in 3
      patients (2 with right and 1 with left lesion). Difficulties in visual gnosia
      were observed in 1 patient with right lesion while word-finding difficulties were
      observed in 1 patient with left lesion. CONCLUSIONS: Our observations show that
      while learning, naming, and gnosic difficulties fit with the classical
      verbal/nonverbal dichotomy (left and right hemisphere, respectively), executive
      dysfunctions, including verbal fluency tasks, were more dominant after right
      thalamic infarcts. Although the observed deficits appeared to be less severe than
      those generally found with dorsomedial and polar thalamic strokes, the dominance
      of executive dysfunction suggests that ventrolateral thalamic lesions may disrupt
      frontothalamic subcortical loops.

PMID- 14568816
TI  - Muscle glycogenosis and mitochondrial hepatopathy in an infant with mutations in
      both the myophosphorylase and deoxyguanosine kinase genes.
AB  - OBJECTIVES: To document 2 apparently incongruous clinical disorders occurring in
      the same infant: congenital myopathy with myophosphorylase deficiency (McArdle
      disease) and mitochondrial hepatopathy with liver failure and mitochondrial DNA
      depletion. METHODS: An infant girl born to consanguineous Moroccan parents had
      severe congenital hypotonia and hepatomegaly, developed liver failure, and died
      at 5 months of age. We studied muscle and liver biopsy specimens histochemically
      and biochemically, and we sequenced the whole coding regions of the
      deoxyguanosine kinase (dGK) and myophosphorylase (PYGM) genes. RESULTS: Muscle
      biopsy specimens showed subsarcolemmal glycogen accumulation and negative
      histochemical reaction for phosphorylase. Liver biopsy specimens showed
      micronodular cirrhosis and massive mitochondrial proliferation. Biochemical
      analysis showed phosphorylase deficiency in muscle and cytochrome c oxidase
      deficiency in liver. We identified a novel homozygous missense G-to-A mutation at
      codon 456 in exon 11 of PYGM, as well as a homozygous 4-base pair GATT
      duplication (nucleotides 763-766) in exon 6 of dGK, which produces a frame shift
      and a premature TGA stop codon at nucleotides 766 to 768, resulting in a
      truncated 255-amino acid protein. Both mutations were absent in 100 healthy
      individuals. CONCLUSIONS: Our data further expand the genetic heterogeneity in
      patients with McArdle disease; confirm the strong relationship between
      mitochondrial DNA depletion syndrome, liver involvement, and dGK mutations; and
      suggest that genetic "double trouble" should be considered in patients with
      unusual severe phenotypes.

PMID- 14568817
TI  - West nile virus encephalitis involving the substantia nigra: neuroimaging and
      pathologic findings with literature review.
AB  - West Nile virus has become a medically important arbovirus in the continental
      United States with its debut in 1999 in the New York City area. We present
      neuroimaging features and pathologic findings in 2 patients who were severely
      affected out of the more that 100 documented cases at our institution. Both
      patients showed striking involvement of the substantia nigra, a finding not
      previously reported for West Nile virus.

PMID- 14568819
TI  - Neuropsychiatric disturbances in presumed late-onset cobalamin C disease.
AB  - BACKGROUND: Combined methylmalonic aciduria and homocystinuria cobalamin C type
      (cobalamin C disease) is an inborn metabolic disorder consisting of an impaired
      intracellular synthesis of the 2 active forms of vitamin B12 (cobalamin), namely,
      adenosylcobalamin and methylcobalamin, that results in increased levels of
      methylmalonic acid and homocysteine in the blood and urine. Most patients present
      in the first year of life with systemic, hematological, and neurological
      abnormalities. Late-onset forms are rare and had not been comprehensively
      characterized. They could be easily misdiagnosed. OBJECTIVE: To describe clinical
      and biochemical features of the disease in 2 siblings affected with presumed late
      onset cobalamin C disease. DESIGN: Case report and review of the literature.
      SETTING: Neurological intensive care unit of a university hospital. OBSERVATION:
      We describe 2 patients with neurological deterioration due to presumed cobalamin
      C disease. A 16-year-old girl was initially seen with psychosis and severe
      progressive neuropathy requiring mechanical ventilatory support and her 24-year
      old sister had a 2-year disease course of subacute combined degeneration of the
      spinal cord. A metabolic workup displayed increased methylmalonic acid levels,
      severe hyperhomocysteinemia, and low plasma methionine levels. The diagnosis was
      then confirmed by demonstration of impaired synthesis of adenosylcobalamin and
      methylcobalamin in cultured skin fibroblasts and Epstein-Barr virus-infected
      lymphocytes. Under specific treatment the younger sister's condition dramatically
      improved. CONCLUSIONS: Although complementation studies have not been conducted,
      it is most likely these patients had cobalamin C disease. This study emphasizes
      the possibility of late-onset disease with purely neurological manifestations.
      Left untreated, this treatable condition can lead to death or irreversible damage
      to the nervous system. Screening for intracellular vitamin B12 dysmetabolism
      should, therefore, be considered in the investigation of adults with unexplained
      neurological disease, particularly when they are initially seen with a clinical
      picture suggestive of vitamin B12 deficiency.

PMID- 14568818
TI  - A case of dementia parkinsonism resembling progressive supranuclear palsy due to
      mutation in the tau protein gene.
AB  - BACKGROUND: Few cases of frontotemporal dementia parkinsonism (FTDP-17) have been
      described in the literature. To our knowledge, this is the first Italian case.
      OBJECTIVE: To report a case of FTDP linked to chromosome 17, exhibiting
      progressive supranuclear palsy on initial examination. PATIENT: A 50-year-old
      woman had a 4-year history of behavior changes associated with slowly progressive
      mental decay and parkinsonism, with poor balance, supranuclear vertical gaze
      palsy, and bradykinesia. The symptoms were not responsive to dopaminergic
      therapy. Her father had died at age 46 years after a 7-year history of
      parkinsonism, and her brother, diagnosed as having progressive supranuclear
      palsy, died at age 45 years. RESULTS: Magnetic resonance imaging showed mild
      midbrain atrophy, results of an electroencephalogram were normal, and cognitive
      evaluation showed moderate cognitive impairment, especially evident in the
      executive and attentional functions. Genetic testing revealed a tau gene mutation
      at codon 279 (AAT-->AAG) of exon 10. CONCLUSION: Exon 10 mutations (including the
      N279K mutation) that result in overproduction of the tau isoform with 4
      microtubule binding motifs seem to be associated with a mainly parkinsonian
      phenotype at disease onset.

PMID- 14568820
TI  - Magnetic resonance imaging of Wallerian degeneration in stroke.

PMID- 14568821
TI  - Aicardi syndrome.
AB  - The astute observations of Aicardi and colleagues led to the first description of
      Aicardi syndrome as a triad of infantile spasms, absence of the corpus callosum,
      and chorioretinal lacunae. Still diagnosed clinically, we now recognize an
      expanded version of this probable X-linked dominant disorder that predominantly
      affects females. In addition to the classic findings, patients typically
      experience intractable epilepsy of multiple seizure types, profound mental
      retardation, and costovertebral anomalies. Associated cerebral and ophthalmologic
      malformations are numerous. This article highlights several seminal citations
      involving the history of the initial description and the characteristic
      ophthalmologic and electroencephalographic features of Aicardi syndrome.

PMID- 14568822
TI  - Bernard Brouwer's lecture tours in the United States (1926 and 1933).
AB  - Bernard Brouwer (1881-1949), the first ordinary professor of neurology in the
      Netherlands and a man of prominent stature among continental neurologists, was
      invited to read lectures at several university clinics in the United States in
      1926 and 1933. In this article, we describe Brouwer's impressions from these
      tours to obtain a view of US neurology in the 1920s and 1930s compared with the
      state of Dutch neurology. We studied Brouwer's reports of the lecture tours and
      pertinent materials obtained from several institutes in the United States where
      he lectured. Brouwer read the Herter Lectures at The Johns Hopkins University
      (Baltimore, Md) in April 1926 and subsequently visited several American cities.
      His second tour was by invitation from the Association for Research in Nervous
      and Mental Disease in New York, NY (1933), and he accepted invitations to visit
      New Haven, Conn; Boston, Mass; and Montreal, Quebec. According to Brouwer,
      neuroanatomy in the United States was studied on a wider experimental basis than
      in Europe. American colleagues, frequently working in teams, tended to have their
      theoretical-scientific work led by direct practical results. The scientific level
      among various universities ranged more widely than in the Netherlands, where the
      levels were homogeneous. In the United States, Brouwer encountered a general
      willingness to engage in scientific investigations, usually manifesting already
      in young students and residents, their inquisitive minds being stimulated early.
      His US colleagues had more assistants in the clinics and laboratories than those
      in the Netherlands. American neurologists were particularly interested in the
      anatomic and physiologic features of the meninges and cerebrospinal fluid
      circulation. American neurosurgeons were vastly advanced in neurosurgery.

PMID- 14568824
TI  - Myasthenia gravis: generalized vs ocular, and children vs adults.

PMID- 14568823
TI  - Development of generalized myasthenia gravis in patients with ocular myasthenia
      gravis.

PMID- 14568825
TI  - Callosal neglect reexamined.

PMID- 14568826
TI  - Callosal neglect and cognitive impersistence.

PMID- 14568827
TI  - Focus on the locus.

PMID- 14568828
TI  - Radiosurgery can achieve precision needed for functional neurosurgery.

PMID- 14568829
TI  - Recalcitrant, recurrent aphthous stomatitis treated with etanercept.

PMID- 14568830
TI  - Combination 532-nm and 1064-nm lasers for noninvasive skin rejuvenation and
      toning.
AB  - BACKGROUND: Noninvasive techniques for skin rejuvenation are quickly becoming
      standard in the treatment of mild rhytids and overall skin toning. Multiple laser
      wavelengths and modalities have been used with varying degrees of success,
      including 532-nm, 585-nm, 1064-nm, 1320-nm, 1450-nm, and 1540-nm wavelengths.
      OBJECTIVES: To evaluate a combination technique using a long-pulsed, 532-nm
      potassium titanyl phosphate (KTP) laser and a long-pulsed 1064-nm Nd:YAG laser,
      separately and combined, for noninvasive photorejuvenation and skin toning and
      collagen enhancement and to establish efficacy and degree of success. DESIGN:
      Prospective nonrandomized study with longitudinal follow-up. SETTING: Private
      dermatologic surgery and laser practice. METHODS: A total of 150 patients, with
      skin types I through V, were treated with long-pulsed KTP 532-nm and long-pulsed
      Nd:YAG 1064-nm lasers, separately and combined. For the KTP 532-nm laser, the
      fluences varied between 7 to 15 J/cm2 at 7- to 20-millisecond pulse durations
      with a 2-mm handpiece and 6 to 15 J/cm2 at 30- to 50-millisecond pulses with a 4
      mm handpiece. The 1064-nm Nd:YAG laser fluences were set at 24 to 30 J/cm2 for a
      10-mm handpiece. These energies were delivered at 30- to 65-millisecond pulse
      durations. All subjects were treated at least 3 times and at most 6 times,
      depending on patient satisfaction level, at monthly intervals and were observed
      for up to 18 months after the last treatment. MAIN OUTCOME MEASURES: All patients
      were asked to fill out a "severity scale" on which redness, pigmentation,
      rhytids, skin tone/tightness, texture, and patient satisfaction were noted before
      and after each treatment. Redness, pigmentation, rhytids, skin tone/tightness,
      and texture were also evaluated by the physician and another observer. RESULTS:
      After 3 to 6 treatments, 50 patients treated with the 532-nm KTP laser alone
      showed improvement of 70% to 80% in redness and pigmentation, 30% to 50% in skin
      tone/tightening, 30% to 40% in skin texture, and 20% to 30% in rhytids. Another
      50 patients treated with the 1064-nm Nd:YAG laser alone showed improvement of 10%
      to 20% in redness, 0% to 10% in pigmentation, 10% to 30% in skin tone/tightening,
      20% to 30% in skin texture, and 10% to 30% in rhytids. The third group of 50
      patients treated with both KTP and Nd:YAG lasers showed improvement of 70% to 80%
      in redness and pigmentation, 40% to 60% in skin tone/tightening, 40% to 60% in
      skin texture, and 30% to 40% in rhytids. Skin biopsy specimens taken at 1-, 2-, 3
      , and 6-month intervals demonstrated new collagen formation. CONCLUSIONS: All 150
      patients exhibited mild to moderate improvement in the appearance of rhytids,
      moderate improvement in skin toning and texture, and great improvement in the
      reduction of redness and pigmentation. The KTP laser used alone produced results
      superior to those of the Nd:YAG laser. Results from combination treatment with
      both KTP and Nd:YAG lasers were slightly superior to those achieved with either
      laser alone.

PMID- 14568831
TI  - Full-face laser resurfacing using a supplemented topical anesthesia protocol.
AB  - BACKGROUND: Laser resurfacing has become a popular modality for the treatment of
      photodamaged skin, rhytids, and acne scarring. In many cases, this procedure is
      performed under general anesthesia or intravenous sedation in conjunction with
      nerve blocks and local infiltration. OBJECTIVE: To evaluate the safety and
      efficacy of facial carbon dioxide laser resurfacing using a supplemented topical
      anesthesia protocol. DESIGN: Nonrandomized case series of patients observed for 1
      year. SETTING: Outpatient surgery center. PATIENTS: Two hundred consecutive
      patients undergoing treatment for facial rhytids or acne scarring. Intervention
      Full-face carbon dioxide laser resurfacing procedures were performed using a
      supplemented topical anesthesia protocol. Pretreatment medications included
      diazepam, oral analgesics, and intramuscular ketorolac tromethamine. MAIN OUTCOME
      MEASURES: Tolerability of procedure, healing times, and adverse effects. RESULTS:
      Topical anesthesia provided effective and sufficient anesthesia in most cases.
      Only 10 of 200 patients required additional anesthesia (regional nerve blocks
      and/or local infiltration). Substantial improvement of rhytids, photodamage, and
      acne scarring was observed. Posttreatment hypopigmentation was seen in 1 patient.
      Scarring was not observed. Conclusion A supplemented topical anesthesia protocol
      for full-face laser resurfacing is a safe and effective alternative to
      traditional anesthesia strategies.

PMID- 14568832
TI  - Laser-assisted penetration of topical anesthetic in adults.
AB  - OBJECTIVE: To determine whether pretreatment of skin with erbium:YAG (Er:YAG)
      laser-assisted delivery facilitates the penetration of lidocaine cream to provide
      anesthesia suitable for needlesticks after just 5 minutes. DESIGN: Trial 1 was a
      double-blind randomized controlled trial, whereas trial 2 was a nonblinded
      randomized controlled trial. SETTING: The study was conducted in 2 facilities, an
      academic and a private clinical research unit. PARTICIPANTS: A total of 320
      healthy volunteers, aged 18 to 65 years and of any Fitzpatrick skin phototype.
      INTERVENTIONS: Trial 1 involved an Er:YAG laser pretreatment to disrupt the
      stratum corneum followed by an application of 4% lidocaine cream on one arm, and
      a laser pretreatment plus placebo on the other arm. Trial 2 involved an
      application of 4% lidocaine cream alone on one arm, and a laser pretreatment
      followed by an application of 4% lidocaine cream on the other arm. MAIN OUTCOME
      MEASURE: Self-reported pain perception on a 100-mm visual analog scale after
      quick insertion and removal of a 25-gauge hypodermic needle on the treatment
      sites. RESULTS: Data from the 2 trials showed that there was a 62% pain reduction
      with laser pretreatment plus lidocaine compared with laser pretreatment plus
      placebo, and a 61% pain reduction with laser pretreatment plus lidocaine,
      compared with lidocaine alone. The decrease in pain in both trials was
      statistically significant (P<.001). Adverse events reported 48 hours after
      treatment were few and mild. CONCLUSION: Treatment with the Er:YAG laser followed
      by lidocaine cream is a safe, effective, and efficient means of inducing skin
      anesthesia that significantly reduces the pain of hypodermic needle insertion.

PMID- 14568834
TI  - A prospective survey of patient experiences after laser skin resurfacing: results
      from 2 1/2 years of follow-up.
AB  - BACKGROUND: Laser skin resurfacing (LSR) is a common cosmetic surgical procedure,
      yet there are no prospective long-term studies on patients' perceptions of their
      procedure. OBJECTIVE: To prospectively document patients' subjective experiences
      after LSR. DESIGN: Twenty-seven consecutive patients who underwent combination
      carbon dioxide/erbium:YAG full-face laser resurfacing for acne scarring or
      photodamage were surveyed at postoperative days 1 and 3, within 1 week, at 3
      weeks, 6 weeks, 3 months, and 30 months and asked standardized questions.
      SETTING: Referral-based academic practice. RESULTS: One day after LSR, 10
      patients (37%) were concerned about the outcome, and 3 (11%) considered it a
      "terrible" experience. At 2.7 days after the procedure, 23 patients (85%) would
      recommend LSR, and after 3.7 days, 24 (89%) would have the procedure again. At 3
      months, the patients' mean rating of appearance was 2.3 (0-3 scale), and all 27
      (100%) felt that their appearance had been improved by LSR. After 30 months, 18
      patients (75%) would recommend the procedure, 17 (71%) would have LSR again, 21
      (88%) felt that their appearance was improved, and final appearance was rated 1.8
      (0-3 scale). Patients undergoing LSR to treat acne scarring were as satisfied as
      patients treated for photodamage. CONCLUSIONS: Data on the evolution of patient
      perspective after LSR can improve patient preparation. This may help the surgeon
      and patient achieve shared, realistic expectations for the postoperative period
      and for long-term results.

PMID- 14568835
TI  - Erbium:YAG laser and cultured epidermis in the surgical therapy of stable
      vitiligo.
AB  - OBJECTIVE: To induce complete and reproducible repigmentation of large "stable"
      vitiligo lesions by means of autologous cultured epidermal grafts using a rapid,
      simple, and minimally invasive surgical procedure. DESIGN: Achromic epidermis was
      removed by means of appropriately settled erbium:YAG laser, and autologous
      epidermal grafts were applied onto the recipient bed. Melanocyte content was
      evaluated by dopa reaction. The percentage of repigmentation was calculated using
      a semiautomatic image analysis system. SETTING: A biosafety level 3-type cell
      culture facility, a surgical ambulatory department, and a dermatological
      department in a hospital. PATIENTS: Twenty-one patients with different types of
      vitiligo were admitted to the study and treated with autologous cultured
      epidermal grafts. Inclusion criteria were failure of at least 2 standard medical
      approaches; no therapy for at least 12 months; no progression of old lesions or
      appearance of new lesions; no Koebner phenomenon within the past 18 months; and
      no autoimmune disorders. RESULTS: The average percentage of repigmentation in 21
      patients was 75.9% (1759.7 cm2 repigmented/2315.8 cm2 transplanted). Three
      patients showed a reactivation of their vitiligo and did not show repigmentation.
      The remaining 18 patients, with 43 distinct lesions, showed an average percentage
      of repigmentation of 90% (1759.7 cm2 repigmented/1953.4 cm2 transplanted).
      CONCLUSIONS: Under appropriate conditions, cultured epidermal grafts induce
      complete repigmentation of stable vitiligo lesions. Erbium:YAG laser surgery can
      supply a fast and precise tool for disepithelialization, hence allowing treatment
      of large vitiligo lesions during a single surgical operation.

PMID- 14568836
TI  - Laser-mediated photodynamic therapy of actinic keratoses.
AB  - OBJECTIVE: To assess the safety and efficacy of the long-pulsed pulsed dye laser
      (LP PDL) (595 nm) with photodynamic therapy (PDT) for treatment of actinic
      keratoses (AKs). DESIGN: Prospective, controlled study with 10-day and 2-, 4-,6-,
      and 8-month follow-ups. SETTING: Clinical research center. PATIENTS Volunteer
      sample of 41 patients (age range, 35-91 years; skin types I-III) with AKs.
      INTERVENTION: Single treatment with application of topical 20% 5-aminolevulinic
      acid for 3 hours or 14 to 18 hours, followed by LP PDL irradiation at 595 nm.
      Controls received LP PDL irradiation alone. MAIN OUTCOME MEASURES: Safety
      assessments, treatment and recovery times, and efficacy assessments, including
      patient mean percentage of lesions cleared and distribution of patients by
      percentage of lesions cleared for different anatomic sites. RESULTS: We observed
      no to slight pain; slight to moderate erythema; no purpura, crusting, or
      scarring; treatment time of 1 lesion per second; and resolution of erythema by 7
      to 14 days. The patient mean (95% confidence interval) percentage of head lesions
      (2620 lesions) cleared after 1 treatment was 99.47% (99.44%-99.50%) at 10 days,
      98.19% (98.15%-98.23%) at 2 months, 92.94% (92.73%-93.14%) at 4 months, 91.65%
      (91.15%-92.15%) at 6 months, and 90.32% (78.10%-100%) at 8 months. For
      extremities (949 lesions), these were 83.1% (81.4%-84.9%) at 10 days, 75.5% (73.4
      77.6) at 2 months, 70.9% (68.9%-72.8%) at 4 months, 92.0% (84.0%-100%) at 6
      months, and 100% at 8 months. For trunk (53 lesions), these were 85% (74%-100%)
      at 10 days, 85% (74%-100%), and 65% (50%-80%) at 4 months. No difference in
      safety or efficacy was found between the 3-hour and 14- to 18-hour incubation
      times. In the laser-only control group, no decrease in lesions was observed.
      Among 31 patients with head lesions, 28 (90%) at 10 days, 19 (70%) at 2 months, 9
      (47%) at 4 months, 5 (42%) at 6 months, and 5 (56%) at 8 months were completely
      (100%) clear following a single treatment. Skin biopsy specimens of nonresponding
      lesions demonstrated a high rate of squamous cell carcinoma and other non-AK
      neoplasms. CONCLUSIONS: Treatment of AKs using LP PDL (595 nm) at nonpurpuric
      parameters following topical application of 5-aminolevulinic acid is safe and
      effective. The advantages may include minimal discomfort, rapid incubation
      treatment and recovery times, excellent posttreatment cosmesis, high efficacy
      rates with respect to head lesions, and practical applicability to large body
      surface areas.

PMID- 14568837
TI  - Mechanisms underlying imiquimod-induced regression of basal cell carcinoma in
      vivo.
AB  - BACKGROUND: Imiquimod is a local immune response modifier that has demonstrated
      potent antiviral and antitumor activity. It enhances innate and acquired immune
      responses via endogenous cytokine production and has proven efficacious in
      clearing superficial basal cell carcinoma (sBCC). OBJECTIVE: To evaluate the
      mechanisms by which topical imiquimod treatment leads to sBCC clearance in vivo.
      DESIGN: A pilot, open-label, nonrandomized study. SETTING: Zurich, Switzerland.
      PATIENTS: Six persons 18 years or older who had nonrecurrent primary tumors that
      had not undergone previous biopsy or treatment but were suitable for treatment by
      surgical excision. The tumors were located on the scalp, extremities, or trunk;
      had a minimum diameter of 1 cm and a maximum diameter of 2 cm; and were
      clinically and histologically consistent with sBCC. INTERVENTIONS: Daily
      application of 5% imiquimod cream 5 times per week for a maximum of 6 weeks. When
      the tumor began to show signs of erosion, it was surgically excised. OUTCOME
      MEASURES: Parameters reflecting tumor apoptotic status (Bcl-2), expression of
      death receptors (Fas and Fas ligand [FasL]), intercellular adhesion molecule
      (ICAM) 1, immunosuppressive microenvironment (interleukin 10), and antigen
      presentation machinery (transporter associated with antigen presentation [TAP] 1)
      before and after imiquimod treatment were evaluated. The changes in the
      interferon gamma messenger RNA (mRNA) levels relative to CD4 and CD8 mRNA were
      assessed using quantitative polymerase chain reaction. RESULTS: Tumor cells
      became more susceptible to apoptosis through decreased Bcl-2 expression after
      treatment with 5% imiquimod cream. Inflammatory infiltrate developed rapidly
      (within 3 to 5 days after treatment initiation) and was associated with the
      enhanced expression of ICAM-1. This early response tended to be a mixed cellular
      response of macrophages and lymphocytes. Interferon gamma was produced by CD4 and
      CD8 T cells. Imiquimod treatment induced a massive increase in macrophage
      peritumoral and intratumoral infiltration. Interleukin 10 was produced by
      infiltrating cells but was not produced by tumor cells. Tumor expression of TAP-1
      and Fas/FasL appeared to be unaffected in the first 5 days of treatment.

PMID- 14568838
TI  - Erythromelalgia: vasculopathy, neuropathy, or both? A prospective study of
      vascular and neurophysiologic studies in erythromelalgia.
AB  - OBJECTIVE: To assess the frequency and type of vascular changes and neurologic
      abnormalities in patients with erythromelalgia. DESIGN: Prospective study of
      patients with no spontaneous symptoms at the time of their visit and with
      provoked symptoms. SETTING: Tertiary referral center. PATIENTS: Sixty-seven
      patients presenting with erythromelalgia at Mayo Clinic, Rochester, Minn, from
      1999 through 2001. INTERVENTIONS: Testing nerve and vascular function in patients
      without symptoms present; testing vascular function after provoking symptoms with
      exercise or by increasing ambient temperature. MAIN OUTCOME MEASURES: In patients
      in whom symptoms could be elicited, vascular function with and without symptoms
      was assessed by measurement of local skin temperature, laser Doppler flow, and
      transcutaneous oximetry. Neurologic assessment included electromyography, nerve
      conduction studies, and autonomic reflex screening (using the quantitative
      sudomotor axon reflex test, adrenergic function testing, heart rate response to
      deep breathing, and the Valsalva ratio). RESULTS: Autonomic reflex screening was
      performed on 57 (85%) of the 67 patients. Of these 57 patients, 46 (81%) had
      abnormal quantitative sudomotor axon reflex test results; 14 (25%) had abnormal
      adrenergic function; and 15 (26%) had abnormal cardiovagal function. Put in
      another way, results were abnormal for 49 (86%) of the 57 patients who had
      autonomic reflex screening. Severe sudomotor abnormalities (ie, absent or
      markedly reduced sweat production) were present in 46 (94%) of these 49 patients;
      14 (29%) had abnormal adrenergic function, and 15 (31%) had a cardiovagal
      abnormality. Electromyography and nerve conduction studies were performed in 24
      (36%) of the 67 patients. Of these 24 patients, 14 (58%) had abnormal
      electromyographic results and 10 (42%) had abnormal nerve conduction study
      results. Vascular function studies, with and without symptoms present, were
      performed in 13 of the 67 patients. During symptoms, the mean temperature of the
      toe skin increased by 7.8 degrees C, and blood flow increased 10.2-fold.
      Paradoxically, mean transcutaneous oximetry measurements did not change.
      CONCLUSION: This prospective study extends and confirms our previous observation
      that, in addition to other forms of neuropathy, most patients with
      erythromelalgia have small-fiber neuropathy.

PMID- 14568839
TI  - Imiquimod: a topically applied link between innate and acquired immunity.

PMID- 14568841
TI  - Energy delivery devices for cutaneous remodeling: lasers, lights, and radio
      waves.

PMID- 14568842
TI  - Vesicles in a patient with a lichenoid eruption--quiz case.

PMID- 14568843
TI  - Palpable purpura in an elderly man.

PMID- 14568844
TI  - Multiple hyperkeratotic nodules on the arms.

PMID- 14568845
TI  - Bandlike frontal hair loss in a 62-year-old woman.

PMID- 14568846
TI  - 1% pimecrolimus cream for atopic dermatitis.

PMID- 14568847
TI  - Treatment of nasolabial folds and jowls with a noninvasive radiofrequency device.

PMID- 14568848
TI  - Optimization of laser treatment safety in conjunction with cryogen spray cooling.

PMID- 14568849
TI  - Cyclosporine-induced pseudoporphyria.

PMID- 14568850
TI  - Terminology and management of dysplastic nevi: responses from 145 dermatologists.

PMID- 14568851
TI  - Topical treatment of pressure ulcers with nerve growth factor: a randomized
      clinical trial.
AB  - BACKGROUND: The prevalence of pressure ulcers of the foot is a major health care
      problem in frail elderly patients. A pressure sore dramatically increases the
      cost of medical and nursing care, and effective treatment has always been an
      essential nursing concern. Management options for pressure ulcers include local
      wound care; surgical repair; and, more recently, topical application of growth
      factors. OBJECTIVE: To examine the effects of topical treatment with nerve growth
      factor in patients with severe, noninfected pressure ulcers of the foot. DESIGN:
      Randomized, double-blind, placebo-controlled trial. SETTING: Teaching nursing
      home of Catholic University of the Sacred Heart, Italy. PATIENTS: 36 persons with
      pressure ulcers of the foot. INTERVENTION: 18 patients received nerve growth
      factor treatment, and 18 patients received only conventional topical treatment.
      MEASUREMENTS: The course of the ulcers during follow-up was evaluated by tracing
      the perimeter of the wound onto sterile, transparent block paper and determining
      the stage. RESULTS: At baseline, the treatment and control groups did not differ
      across demographic variables, clinical characteristics, and functional measures.
      The mean area (+/-SD) of the ulcers was 1012 +/- 633 mm2 in the treatment group
      and 1012 +/- 655 mm2 in the control group (P > 0.2). The average reduction in
      pressure ulcer area at 6 weeks was statistically significantly greater in the
      treatment group than in the control group (738 +/- 393 mm2 vs. 485 +/- 384 mm2; P
      = 0.034). CONCLUSION: Topical application of nerve growth factor may be an
      effective therapy for patients with severe pressure ulcers.

PMID- 14568852
TI  - Serum insulin-like growth factor I and risk for heart failure in elderly
      individuals without a previous myocardial infarction: the Framingham Heart Study.
AB  - BACKGROUND: Several experimental investigations have emphasized the favorable
      effects of insulin-like growth factor I (IGF-I) on left ventricular remodeling,
      partly through its antiapoptotic effects. Cross-sectional clinical studies have
      reported that low serum IGF-I levels in patients with heart failure correlate
      with cachexia and severity of ventricular dysfunction. It is unclear whether low
      serum IGF-I is a risk factor for heart failure. OBJECTIVE: To prospectively study
      the association between serum IGF-I level and the incidence of congestive heart
      failure. DESIGN: Community-based, prospective cohort study. SETTING: Framingham,
      Massachusetts. PARTICIPANTS: 717 elderly individuals (mean age, 78.4 years; 67%
      women) who did not have myocardial infarction and congestive heart failure at
      baseline. MEASUREMENT: Incidence of a first episode of congestive heart failure
      on follow-up. RESULTS: During follow-up (mean, 5.2 years), 56 participants (35
      women) developed congestive heart failure. In multivariable Cox regression models
      adjusting for established risk factors at baseline, there was a 27% decrease in
      risk for heart failure for every 1 standard deviation increment in log IGF-I.
      Individuals with serum IGF-I level at or above the median value (140 microg/L)
      had half the risk for heart failure (hazard ratio, 0.49 [95% CI, 0.26 to 0.92])
      of those with serum IGF-I levels below the median. These comparisons were
      maintained in analyses adjusting for the occurrence of a myocardial infarction on
      follow-up. CONCLUSIONS: In our prospective, community-based investigation, serum
      IGF-I level was inversely related to the risk for congestive heart failure in
      elderly people without a previous myocardial infarction. Additional
      investigations are warranted to confirm these findings.

PMID- 14568853
TI  - Association of hospital procedure volume and outcomes in patients with colon
      cancer at high risk for recurrence.
AB  - BACKGROUND: Studies that use registry data have demonstrated superior long-term
      overall survival after curative surgical resection of colon cancer at hospitals
      where the volume of such surgeries is high. However, because such administrative
      data lack information on cancer recurrence, the true nature of this relation
      remains uncertain. OBJECTIVE: To determine whether hospital procedure volume
      predicts long-term outcomes of colon cancer surgery. DESIGN: Nested cohort study
      within a randomized clinical trial. SETTING: Intergroup 0089 national adjuvant
      colon cancer study conducted between 1988 and 1992. PATIENTS: 3161 patients with
      high-risk stage II and stage III colon cancer. MEASUREMENTS: Overall survival and
      recurrence-free survival, by hospital procedure volume as defined by Medicare
      claims data. RESULTS: With a median follow-up of 9.4 years, 5-year overall
      survival significantly differed across tertiles of hospital procedure volume
      (63.8% for patients who had resection at low-volume hospitals compared with 67.3%
      at high-volume hospitals; P = 0.04). After adjustment for other predictors of
      colon cancer outcome, the hazard ratio for overall mortality in patients treated
      at low-volume centers was 1.16 (95% CI, 1.03 to 1.32). However, the risk for
      cancer recurrence was not associated with hospital procedure volume. Five-year
      recurrence-free survival was 63.9% for patients who had resection at low-volume
      hospitals compared with 63.0% at high-volume hospitals (adjusted hazard ratio,
      1.03 [CI, 0.89 to 1.18]). These findings did not materially change after
      stratification by other potential demographic and clinical predictors of outcome.
      CONCLUSIONS: According to prospectively recorded data from a large clinical
      trial, patients whose colon cancer was resected at low-volume hospitals
      experienced a higher risk for long-term mortality; however, this increased
      mortality was not attributable to differences in colon cancer recurrences.

PMID- 14568854
TI  - The effect of clustering of outcomes on the association of procedure volume and
      surgical outcomes.
AB  - BACKGROUND: A large body of literature documents associations between the volume
      of cases a hospital or surgeon treats and clinical outcomes. Most of these
      studies have used conventional statistical methods that do not recognize the fact
      that hospitals or surgeons with similar volumes may have very different outcomes
      because of systematic differences in processes of care, a phenomenon that
      exaggerates the true statistical significance of the effect of volume on outcome.
      OBJECTIVE: To describe methods to assess the degree of this "clustering" of
      outcomes and to explore the impact of available statistical techniques that
      correct for clustering. DESIGN: Reanalysis of 3 previously published volume
      outcome studies. SETTING: Medicare beneficiaries 65 years of age or older
      undergoing surgery for colon, prostate, or rectal cancer in the population
      defined by the Surveillance, Epidemiology, and End Results cancer registries
      during 1992 to 1996. PATIENTS: 3 data sets were analyzed to assess the impact of
      surgeon volume on outcomes: 1) 24 166 colectomies performed by 2682 surgeons, 2)
      10 737 prostatectomies performed by 999 surgeons, and 3) 2603 rectal resections
      performed by 1141 surgeons. MEASUREMENTS: Volume-outcome trends were analyzed by
      a conventional method (logistic regression) and corrected for clustering. Two
      widely used statistical methods for analyzing clustered data, a random-effects
      model and generalized estimating equations, were used and compared, and the
      degree of clustering was presented graphically. RESULTS: Substantial clustering
      was observed in the analyses involving morbidity end points. The 2 statistical
      techniques produced noticeably different results in some analyses. CONCLUSIONS:
      The presence of clustering represents variations in outcomes among providers with
      similar volumes. Thus, in volume-outcome studies, the degree of clustering of
      outcomes should be characterized because it may provide insight into variations
      in quality of care.

PMID- 14568855
TI  - Update in oncology.

PMID- 14568856
TI  - Effects of statins on nonlipid serum markers associated with cardiovascular
      disease: a systematic review.
AB  - BACKGROUND: Statins reduce cardiovascular events to a greater extent than can be
      explained by their effect on lipids. Several studies have attempted to elucidate
      mechanisms by which statins reduce cardiovascular risk. PURPOSE: To summarize the
      effects of statins on nonlipid serum markers and to correlate statins' effect on
      serum markers with lipid levels and cardiovascular outcomes. DATA SOURCES:
      MEDLINE (1980 to 2003) search limited to English-language articles. STUDY
      SELECTION: Studies reporting original data in at least 10 participants on the
      effect of statins on outcomes of interest, excluding studies of cerivastatin,
      drug combinations, and patients with organ transplants. DATA EXTRACTION: Study
      design, sample size, treatment, and outcome data extracted on the basis of
      preestablished criteria. When appropriate, meta-analysis was performed by using a
      random-effects model. DATA SYNTHESIS: All statins are effective at lowering C
      reactive protein levels, and the effect is not dose-dependent. Studies do not
      demonstrate a correlation between statins' effects on C-reactive protein levels
      and on lipids or cardiovascular outcomes. Statins do not affect fibrinogen
      levels, and limited data suggest little effect on lipid oxidation, tissue
      plasminogen activator, or plasminogen activator inhibitor. Platelet aggregation
      data are inconclusive. CONCLUSIONS: Among nonlipid serum markers examined, only C
      reactive protein levels are statistically significantly affected by statins.
      These findings suggest that statin-mediated anti-inflammatory effects may
      contribute to the ability of statins to reduce risk for cardiovascular disease.
      Overall, however, available data are insufficient to support recommendations for
      using nonlipid serum markers in decisions regarding statin therapy for individual
      patients.

PMID- 14568857
TI  - Delayed drug hypersensitivity reactions.
AB  - Immune reactions to small molecular compounds, such as drugs, can cause a variety
      of diseases involving the skin, liver, kidney, and lungs. In many drug
      hypersensitivity reactions, drug-specific CD4+ and CD8+ T cells recognize drugs
      through their alphabeta T-cell receptors in an MHC-dependent way. Drugs stimulate
      T cells if they act as haptens and bind covalently to peptides or if they have
      structural features that allow them to interact with certain T-cell receptors
      directly. Immunohistochemical and functional studies of drug-reactive T cells in
      patients with distinct forms of exanthema reveal that distinct T-cell functions
      lead to different clinical phenotypes. In maculopapular exanthema, perforin
      positive and granzyme B-positive CD4+ T cells kill activated keratinocytes, while
      a large number of cytotoxic CD8+ T cells in the epidermis is associated with
      formation of vesicles and bullae. Drug-specific T cells also orchestrate
      inflammatory skin reactions through the release of various cytokines (for
      example, interleukin-5, interferon) and chemokines (such as interleukin-8).
      Activation of T cells with a particular function seems to lead to a specific
      clinical picture (for example, bullous or pustular exanthema). Taken together,
      these data allow delayed hypersensitivity reactions (type IV) to be further
      subclassified into T-cell reactions, which through the release of certain
      cytokines and chemokines preferentially activate and recruit monocytes (type
      IVa), eosinophils (type IVb), or neutrophils (type IVd). Moreover, cytotoxic
      functions by either CD4+ or CD8+ T cells (type IVc) seem to participate in all
      type IV reactions.

PMID- 14568858
TI  - The promise of topical growth factors in healing pressure ulcers.

PMID- 14568859
TI  - Does practice really make perfect?

PMID- 14568860
TI  - A sudden change in vision.

PMID- 14568861
TI  - Hospitalist care.

PMID- 14568862
TI  - Hospitalist care.

PMID- 14568863
TI  - Notice of retraction.

PMID- 14568864
TI  - Hospitalist care.

PMID- 14568865
TI  - Hospitalist care.

PMID- 14568866
TI  - CPR for patients labeled DNR.

PMID- 14568867
TI  - CPR for patients labeled DNR.

PMID- 14568868
TI  - CPR for patients labeled DNR.

PMID- 14568869
TI  - CPR for patients labeled DNR.

PMID- 14568870
TI  - The hungry bone syndrome after medical treatment of thyrotoxicosis.

PMID- 14568871
TI  - Unexpected risks during administration of conscious sedation: previously
      undiagnosed obstructive sleep apnea.

PMID- 14568872
TI  - HFE gene mutations in Chile.

PMID- 14568873
TI  - Should doctors prescribe alcohol to adults?

PMID- 14568874
TI  - Summaries for patients. Nerve growth factor improves healing of pressure ulcers
      of the foot.

PMID- 14568875
TI  - Summaries for patients. Insulin-like growth factor I levels and heart failure
      risk in older people.

PMID- 14568876
TI  - Summaries for patients. Relationships between the amount of colon cancer surgery
      a hospital performs and patient outcomes.

PMID- 14568877
TI  - Summaries for patients. Choice of statistical analysis can change the results of
      studies of the relationship between hospital and surgeon volume and outcomes of
      cancer surgery.

PMID- 14568878
TI  - Summaries for patients. Delayed drug hypersensitivity.

PMID- 14568880
TI  - A critical overview of homeopathy.

PMID- 14568879
TI  - A critical overview of homeopathy.

PMID- 14568881
TI  - A critical overview of homeopathy.

PMID- 14568882
TI  - Maturational factors modulate transcription factors CCAAT/enhancer-binding
      proteins alpha, beta, delta, and peroxisome proliferator-activated receptor-gamma
      in fetal rat lung epithelial cells.
AB  - Previous investigations have evidenced the importance of CCAAT/enhancer-binding
      proteins (C/EBPs) and peroxisome proliferator-activated receptor (PPAR)gamma for
      lung development, especially for alveolar type II cells (ATII). This prompted us
      to explore whether ATII maturation-promoting mediators controlled their
      expression in isolated ATII. In whole rat lung, C/EBPalpha, beta, delta, and
      PPARgamma mRNAs increased 3-5 times between gestational day 18 and term (Day 22),
      dropped around birth, then reincreased. C/EBPbeta and delta, but not PPARgamma,
      displayed similar profile in isolated ATII; C/EBPalpha transcript disappeared and
      the protein became hardly detectable in isolated cells. In cultured ATII,
      dexamethasone increased C/EBPbeta and PPARgamma mRNAs 2-4 times, and cyclic AMP
      increased C/EBPbeta and delta mRNAs approximately 1.5 times. Whereas retinoic
      acid increased C/EBPbeta and PPARgamma mRNAs 1.5 times in ATII in vitro, vitamin
      A deficiency strongly decreased fetal lung C/EBPalpha, beta, and PPARgamma
      transcripts in vivo. C/EBPbeta, delta, and PPARgamma mRNAs were also increased in
      vitro by epidermal growth factor and keratinocyte growth factor, whereas they
      were unchanged by the maturation inhibitor transforming growth factor-beta.
      C/EBPalpha expression was not reinduced by any mediator. Changes in transcripts
      were reflected in protein levels analyzed through Western blotting. These results
      argue for a role of these factors in ATII functional maturation, and indicate a
      multifactorial control of their ontogeny.

PMID- 14568883
TI  - Protein processing and degradation in pulmonary health and disease.

PMID- 14568884
TI  - Oxidative stress and cardiovascular injury: Part I: basic mechanisms and in vivo
      monitoring of ROS.

PMID- 14568885
TI  - New markers of inflammation and endothelial cell activation: Part I.

PMID- 14568886
TI  - Images in cardiovascular medicine. Transient left ventricular apical ballooning.

PMID- 14568887
TI  - Nonvalvular cardiovascular device-related infections.

PMID- 14568888
TI  - Cardiology patient page. Kidney failure and cardiovascular disease.

PMID- 14568889
TI  - Images in cardiovascular medicine. Simultaneous "Tirone David-V" valve-sparing
      aortic root replacement and radical mitral valve repair for the Marfan syndrome
      with Barlow syndrome.

PMID- 14568890
TI  - A new marker?

PMID- 14568891
TI  - Comparison of coronary thermodilution and Doppler velocity for assessing coronary
      flow reserve.
AB  - BACKGROUND: Thermodilution coronary flow reserve (CFRthermo) is a new technique
      for invasively measuring coronary flow reserve (CFR) with a coronary pressure
      wire and is based on the ability of the pressure transducer to also measure
      temperature changes. Whether CFRthermo correlates well enough with absolute flow
      derived CFR (CFRflow) to replace Doppler wire-derived CFR (CFRDoppler) remains
      unclear. METHODS AND RESULTS: In an open-chest pig model, CFRthermo was measured
      in the left anterior descending (LAD) artery and compared with CFRDoppler and
      CFRflow, measured with an external flow probe placed around the LAD. In 9 pigs,
      CFR was measured simultaneously by all 3 means in the normal LAD and after
      creation of an epicardial LAD stenosis. To determine the added effect of
      microvascular disease, measurements of flow reserve were also performed after
      disruption of the coronary microcirculation with embolized microspheres.
      Intracoronary papaverine (20 mg) was used to induce hyperemia. In a total of 61
      paired measurements, CFRthermo correlated strongly with the reference standard
      CFRflow (r=0.85, P<0.001). CFRDoppler correlated less well with CFRflow (r=0.72,
      P<0.001). Bland-Altman analysis showed a closer agreement between CFRthermo and
      CFRflow. CONCLUSIONS: CFRthermo correlates better with CFRflow than does
      CFRDoppler.

PMID- 14568892
TI  - Effects of statins on platelet inhibition by a high loading dose of clopidogrel.
AB  - BACKGROUND: Recent studies suggested that some HMG-CoA reductase blockers might
      inhibit the antiplatelet activity of clopidogrel. Therefore, we analyzed how
      various statins together with a high loading dose of clopidogrel (600 mg) affect
      platelet aggregation. METHODS AND RESULTS: Seventy-seven patients with stable
      angina scheduled for elective coronary stenting were studied. Patients were
      randomized to receive atorvastatin, fluvastatin, lovastatin, pravastatin,
      simvastatin (each 20 mg), cerivastatin (0.3 mg), or placebo, plus a high loading
      dose of 600 mg of clopidogrel. ADP-induced platelet aggregation (5 and 20
      micromol/L) was determined before and 2 and 4 hours after first clopidogrel
      administration. All patients were taking aspirin (100 mg/d) regularly. We found
      that none of the statins significantly influenced inhibition of platelet
      aggregation by clopidogrel. CONCLUSIONS: Concomitant use of statins with
      clopidogrel does not significantly inhibit antiplatelet activity, at least when
      clopidogrel is administered at a high loading dose of 600 mg.

PMID- 14568893
TI  - Long-term treatment with oral sildenafil is safe and improves functional capacity
      and hemodynamics in patients with pulmonary arterial hypertension.
AB  - BACKGROUND: The prognosis and functional capacity of patients with pulmonary
      arterial hypertension (PAH) is poor, and there is a need for safe, effective,
      inexpensive oral treatments. A single dose of sildenafil, an oral
      phosphodiesterase type-5 (PD-5) inhibitor, is an effective and selective
      pulmonary vasodilator in PAH. However, the long-term effects of PD-5 inhibition
      and its mechanism of action in human pulmonary arteries (PAs) are unknown.
      METHODS AND RESULTS: We hypothesized that 3 months of sildenafil (50 mg orally
      every 8 hours) added to standard treatment would be safe and improve functional
      capacity and hemodynamics in PAH patients. We studied 5 consecutive patients (4
      with primary pulmonary hypertension, 1 with Eisenmenger's syndrome; New York
      Heart Association class II to III). Functional class improved by > or =1 class in
      all patients. Pretreatment versus posttreatment values (mean+/-SEM) were as
      follows: 6-minute walk, 376+/-30 versus 504+/-27 m, P<0.0001; mean PA pressure,
      70+/-3 versus 52+/-3 mm Hg, P<0.007; pulmonary vascular resistance index 1702+/
      151 versus 996+/-92 dyne x s x cm(-5) x m(-2), P<0.006. The systemic arterial
      pressure was unchanged, and no adverse effects occurred. Sildenafil also reduced
      right ventricular mass measured by MRI. In 7 human PAs (6 cardiac transplant
      donors and 1 patient with PAH on autopsy), we showed that PD-5 is present in PA
      smooth muscle cells and that sildenafil causes relaxation by activating large
      conductance, calcium-activated potassium channels. CONCLUSIONS: This small pilot
      study suggests that long-term sildenafil therapy might be a safe and effective
      treatment for PAH. At a monthly cost of 492 dollars Canadian, sildenafil is more
      affordable than most approved PAH therapies. A large multicenter trial is
      indicated to directly compare sildenafil with existing PAH treatments.

PMID- 14568894
TI  - Transdifferentiation of human peripheral blood CD34+-enriched cell population
      into cardiomyocytes, endothelial cells, and smooth muscle cells in vivo.
AB  - BACKGROUND: Adult human peripheral blood cells have been shown to differentiate
      into mature cells of nonhematopoietic tissues, such as hepatocytes and epithelial
      cells of the skin and gastrointestinal track. We investigated whether these cells
      could also transdifferentiate into human cardiomyocytes, mature endothelial
      cells, and smooth muscle cells in vivo. METHODS AND RESULTS: Myocardial
      infarction was created in SCID mice by occluding the left anterior descending
      coronary artery, after which adult peripheral blood CD34+ cells were injected
      into the tail vein. Hearts were harvested 2 months after injection and stained
      for human leukocyte antigen (HLA) and markers for cardiomyocytes, endothelial
      cells, and smooth muscle cells. Cardiomyocytes, endothelial cells, and smooth
      muscle cells that bear HLA were identified in the infarct and peri-infarct
      regions of the mouse hearts. In a separate experiment, CD34+ cells were injected
      intraventricularly into mice without experimental myocardial infarction. HLA
      positive myocytes and smooth muscle cells could only be identified in 1 of these
      mice killed at different time points. CONCLUSIONS: Adult peripheral blood CD34+
      cells can transdifferentiate into cardiomyocytes, mature endothelial cells, and
      smooth muscle cells in vivo. However, transdifferentiation is augmented
      significantly by local tissue injury. The use of peripheral blood CD34+ cells for
      cell-based therapy should greatly simplify the procurement of cells for the
      regeneration of damaged myocardium.

PMID- 14568895
TI  - Inflammatory markers and onset of cardiovascular events: results from the Health
      ABC study.
AB  - BACKGROUND: Inflammation plays an important role in cardiovascular disease. The
      aim of this study is to investigate the predictive value of several inflammatory
      markers on the incidence of cardiovascular events in well-functioning older
      persons. METHODS AND RESULTS: The subjects were 2225 participants 70 to 79 years
      old, without baseline cardiovascular disease, who were enrolled in the Health,
      Aging, and Body Composition study. Incident coronary heart disease (CHD), stroke,
      and congestive heart failure (CHF) events were detected during an average follow
      up of 3.6 years. Blood levels of interleukin-6 (IL-6), C-reactive protein (CRP),
      and tumor necrosis factor-alpha (TNF-alpha) were assessed. After adjustment for
      potential confounders, IL-6 was significantly associated with all outcomes (CHD
      events, per IL-6 SD increase: RR, 1.27; 95% CI, 1.10 to 1.48; stroke events, per
      IL-6 SD increase: RR, 1.45; 95% CI, 1.12 to 1.86; CHF events, per IL-6 SD
      increase: RR, 1.72; 95% CI, 1.40 to 2.12). TNF-alpha showed significant
      associations with CHD (per TNF-alpha SD increase: RR, 1.22; 95% CI, 1.04 to 1.43)
      and CHF (per TNF-alpha SD increase: RR, 1.59; 95% CI, 1.30 to 1.95) events. CRP
      was significantly associated with CHF events (per CRP SD increase: RR, 1.48; 95%
      CI, 1.23 to 1.78). A composite summary indicator of inflammation showed a strong
      association with incident cardiovascular events, with an especially high risk if
      all 3 inflammatory markers were in the highest tertile. CONCLUSIONS: Findings
      suggest that inflammatory markers are independent predictors of cardiovascular
      events in older persons.

PMID- 14568896
TI  - Mobilized endothelial progenitor cells by granulocyte-macrophage colony
      stimulating factor accelerate reendothelialization and reduce vascular
      inflammation after intravascular radiation.
AB  - BACKGROUND: Endothelial progenitor cells (EPCs) play a pivotal role in repair and
      regeneration of damaged vessels. We investigated the role of mobilized EPCs in
      the healing process after intravascular radiation therapy. METHODS AND RESULTS:
      One iliac artery of hypercholesterolemic rabbits was subjected to balloon injury
      and intravascular radiation with a Re-188 balloon and the contralateral iliac
      artery to balloon injury only. Rabbits received granulocyte-macrophage colony
      stimulating factor (recombinant human GM-CSF) (60 microg/d subcutaneously) daily
      for 1 week, either 7 days before the angioplasty or at the time of angioplasty.
      Control rabbits received human albumin. GM-CSF significantly increased the double
      positive (CD31+ and KDR+) fraction in peripheral blood monocytes and showed a
      higher number of EPCs than albumin after culture and, furthermore, enhanced
      migration and incorporation of EPCs. In the albumin group, intravascular
      radiation therapy reduced neointimal hyperplasia but delayed reendothelialization
      and aggravated monocyte infiltration. GM-CSF treatment significantly accelerated
      the reendothelialization and inhibited monocyte infiltration
      (reendothelialization index, 81+/-13% in the GM-CSF radiation [n=7] versus 30+/
      11% in the control radiation [n=9] at 2 weeks, P<0.01). GM-CSF treatment produced
      an additional significant reduction in neointimal formation at 14 and 28 days
      after injury in the intravascular radiation groups (intima to media ratio, 0.14+/
      0.11 in the GM-CSF radiation [n=5] versus 0.36+/-0.07 in the control radiation
      [n=5] at 4 weeks, P<0.01). CONCLUSIONS: GM-CSF treatment mobilizes EPCs,
      accelerates reendothelialization, and reduces monocytes infiltration after
      intravascular radiation therapy, suggesting that stem cell mobilization is a
      promising strategy for enhancing the vascular healing process after cytotoxic
      angioplasty.

PMID- 14568897
TI  - Anaphylactic and anaphylactoid reactions associated with lepirudin in patients
      with heparin-induced thrombocytopenia.
AB  - BACKGROUND: Lepirudin (Refludan) is a hirudin derivative. It is a direct thrombin
      inhibitor obtained by recombinant technology from the medicinal leech and is
      approved for treatment of heparin-induced thrombocytopenia complicated by
      thrombosis. Because 3 cases of fatal anaphylaxis possibly associated with use of
      lepirudin have been reported, we initiated an investigation of putative lepirudin
      associated anaphylaxis. METHODS AND RESULTS: Aided by the manufacturer (Schering
      AG, Berlin, Germany), we used the lepirudin study databases to identify all
      patients in whom possible anaphylaxis/severe allergy was recorded from 1994 to
      September 2002. The 26 possible cases identified were reviewed independently by 2
      investigators. After excluding patients with mild skin reactions, reactions
      likely caused by concomitant medications, poorly documented cases, and reactions
      that did not correspond temporally with lepirudin use, there remained 9 patients
      judged to have had severe anaphylaxis in close temporal association with
      lepirudin. All reactions occurred within minutes of intravenous lepirudin
      administration, with 4 fatal outcomes (3 acute cardiorespiratory arrests, 1
      hypotension-induced myocardial infarction). In these 4 cases, a previous
      uneventful treatment course with lepirudin was identified (1 to 12 weeks
      earlier). We recorded high-titer IgG-anti-lepirudin antibodies in an additional
      patient with anaphylaxis. Because lepirudin has been used in approximately 35 000
      patients, the risk of anaphylaxis is approximately 0.015% (5 of 32 500) on first
      exposure and 0.16% (4 of 2500) in reexposed patients (7.5% estimated
      reexposures). CONCLUSIONS: Lepirudin can cause fatal anaphylaxis, particularly in
      patients who are treated within 3 months of a previous exposure. The overall
      risk/benefit assessment of lepirudin as a treatment for heparin-induced
      thrombocytopenia remains favorable.

PMID- 14568898
TI  - Comparison of standard cardiopulmonary resuscitation versus the combination of
      active compression-decompression cardiopulmonary resuscitation and an inspiratory
      impedance threshold device for out-of-hospital cardiac arrest.
AB  - BACKGROUND: Active compression-decompression (ACD) CPR combined with an
      inspiratory impedance threshold device (ITD) improves vital organ blood flow
      during cardiac arrest. This study compared survival rates with ACD+ITD CPR versus
      standard manual CPR (S-CPR). METHODS AND RESULTS: A prospective, controlled trial
      was performed in Mainz, Germany, in which a 2-tiered emergency response included
      early defibrillation. Patients with out-of-hospital arrest of presumed cardiac
      pathogenesis were sequentially randomized to ACD+ITD CPR or S-CPR by the advanced
      life support team after intubation. Rescuers learned which method of CPR to use
      at the start of each work shift. The primary end point was 1-hour survival after
      a witnessed arrest. With ACD+ITD CPR (n=103), return of spontaneous circulation
      and 1- and 24-hour survival rates were 55%, 51%, and 37% versus 37%, 32%, and 22%
      with S-CPR (n=107) (P=0.016, 0.006, and 0.033, respectively). One- and 24-hour
      survival rates in witnessed arrests were 55% and 41% with ACD+ITD CPR versus 33%
      and 23% in control subjects (P=0.011 and 0.019), respectively. One- and 24-hour
      survival rates in patients with a witnessed arrest in ventricular fibrillation
      were 68% and 58% after ACD+ITD CPR versus 27% and 23% after S-CPR (P=0.002 and
      0.009), respectively. Patients randomized > or =10 minutes after the call for
      help to the ACD+ITD CPR had a 3 times higher 1-hour survival rate than control
      subjects (P=0.002). Hospital discharge rates were 18% after ACD+ITD CPR versus
      13% in control subjects (P=0.41). In witnessed arrests, overall neurological
      function trended higher with ACD+ITD CPR versus control subjects (P=0.07).
      CONCLUSIONS: Compared with S-CPR, ACD+ITD CPR significantly improved short-term
      survival rates for patients with out-of-hospital cardiac arrest. Additional
      studies are needed to evaluate potential long-term benefits of ACD+ITD CPR.

PMID- 14568900
TI  - Cariporide (HOE642), a selective Na+-H+ exchange inhibitor, inhibits the
      mitochondrial death pathway.
AB  - BACKGROUND: The Na+-H+ exchanger figures prominently in cardiac ischemia
      reperfusion injury. Several experimental and clinical studies have demonstrated a
      cardioprotective effect of Na+-H+ exchanger inhibition; however, the precise
      mechanisms have not been established. METHODS AND RESULTS: We examined the
      effects of cariporide (HOE642, 10 micromol/L) on cell death induced by oxidative
      stress (H2O2, 100 micromol/L) in cultured neonatal rat cardiomyocytes. Cariporide
      significantly suppressed markers of cell death, such as TUNEL positivity and
      caspase-3 cleavage, at 8 or 16 hours after H2O2. The early phase of cell death,
      reported by increases in phosphatidylserine exposure and propidium iodide uptake,
      was also inhibited by cariporide. To explore the mechanisms of cell protection,
      we examined the effects of cariporide on increases in intracellular Na+ and Ca2+
      induced by oxidative stress. Cariporide remarkably suppressed cytosolic Na+ and
      Ca2+ accumulation. Next, we investigated the effects of cariporide on
      mitochondria-associated death process. Mitochondrial Ca2+ overload induced by
      H2O2 was remarkably suppressed by cariporide. Loss of mitochondrial membrane
      potential is a critical step of the death pathway; cariporide prevented
      mitochondrial membrane potential loss induced by H2O2. CONCLUSIONS: Cariporide
      protects cardiomyocytes against oxidant-induced cell death by preserving
      intracellular ion homeostasis and mitochondrial integrity.

PMID- 14568899
TI  - Practical value of cardiac magnetic resonance imaging for clinical quantification
      of aortic valve stenosis: comparison with echocardiography.
AB  - BACKGROUND: Valvular pathology can be analyzed quickly and accurately through the
      use of Doppler ultrasound. For aortic stenosis, the continuity equation approach
      with Doppler velocity-time integral (VTI) data is by far the most commonly used
      clinical method of quantification. In view of the emerging popularity of cardiac
      magnetic resonance (CMR) as a routine clinical imaging tool, the purposes of this
      study were to define the reliability of velocity-encoded CMR as a routine method
      for quantifying stenotic aortic valve area, to compare this method with the
      accepted standard, and to evaluate its reproducibility. METHODS AND RESULTS:
      Patients (n=24) with aortic stenosis (ranging from 0.5 to 1.8 cm2) were imaged
      with CMR and echocardiography. Velocity-encoded CMR was used to obtain velocity
      information in the aorta and left ventricular outflow tract. From this flow data,
      pressure gradients were estimated by means of the modified Bernoulli equation,
      and VTIs were calculated to estimate aortic valve orifice dimensions by means of
      the continuity equation. The correlation coefficients between modalities for
      pressure gradients were r=0.83 for peak and r=0.87 for mean. The measurements of
      VTI correlated well, leading to an overall strong correlation between modalities
      for the estimation of valve dimension (r=0.83, by means of the identified best
      approach). For 5 patients, the CMR examination was repeated using the best
      approach. The repeat calculations of valve size correlated well (r=0.94).
      CONCLUSIONS: Velocity-encoded CMR can be used as a reliable, user-friendly tool
      to evaluate stenotic aortic valves. The measurements of pressure gradients, VTIs,
      and the valve dimension correlate well with the accepted standard of Doppler
      ultrasound.

PMID- 14568902
TI  - Time-dependent and tissue-specific accumulation of mtDNA and respiratory chain
      defects in chronic doxorubicin cardiomyopathy.
AB  - BACKGROUND: Doxorubicin causes a chronic cardiomyopathy of unknown pathogenesis.
      We investigated whether acquired defects in mitochondrial DNA (mtDNA) and
      interconnected respiratory chain dysfunction may represent a molecular mechanism
      for its late onset. METHODS AND RESULTS: Rats were treated weekly with
      intravenous doxorubicin (1 mg/kg) for 7 weeks, starting at 11 weeks of age (group
      B). Controls received saline. Group C received doxorubicin identically to group
      B, but the course was started at 41 weeks of age. All rats were killed at week
      48. Doxorubicin was also injected once, either 6 days (group D) or 2 hours (group
      E) before euthanasia. Heart and skeletal muscle were examined. Only group B rats
      developed a significant clinical, macroscopic, histological, and ultrastructural
      cardiomyopathy. Group B hearts had the lowest cytochrome c oxidase (COX) activity
      (24% of controls; P=0.003), the highest citrate synthase activity (135% of
      controls; P=0.005), and the highest production of superoxide. In group B, the
      respiratory subunit COXI, which is encoded by mtDNA, was reduced (P<0.001), as
      was mtDNA (49% of controls, P<0.001). Group C hearts differed from group B in
      their lower cardiomyopathy score (P=0.006), higher COX activity (P=0.02), and
      higher mtDNA content (P=0.04). Group B and to a lesser extent group C hearts
      contained deleted mtDNA. There was no detectable mitochondrial toxicity in group
      D and E hearts or in skeletal muscle. CONCLUSIONS: In doxorubicin cardiomyopathy,
      mtDNA alterations, superoxide, and respiratory chain dysfunction accumulate long
      term in the absence of the drug and are associated with a late onset.

PMID- 14568901
TI  - Enhanced therapeutic angiogenesis by cotransfection of prostacyclin synthase gene
      or optimization of intramuscular injection of naked plasmid DNA.
AB  - BACKGROUND: Although clinical trials of therapeutic angiogenesis by angiogenic
      growth factors with intramuscular injection of naked plasmid DNA have been
      successful, there are still unresolved problems such as low transfection
      efficiency. From this viewpoint, we performed the following modifications: (1)
      combination with vasodilation using prostacyclin and (2) changing the agents or
      volume of naked plasmid DNA in vivo. METHODS AND RESULTS: First, we examined
      cotransfection of the VEGF gene with the prostacyclin synthase gene in a mouse
      hindlimb ischemia model. Cotransfection of the VEGF gene with the prostacyclin
      synthase gene resulted in a further increase in blood flow and capillary density
      compared with single VEGF gene. Similar results were obtained with other
      angiogenic growth factors, such as hepatocyte growth factor (HGF). Alternatively,
      we changed the injection volume of the solution of plasmid DNA. Luciferase
      activity was increased in a volume-dependent manner. An increase in injection
      volume at 1 site rather than separate injections at multiple sites resulted in
      high transfection efficiency, which suggests that transfection of naked plasmid
      DNA is mediated by pressure. Interestingly, treatment with hyperbaric oxygen
      increased the transfection efficiency. Finally, we also examined the effects of
      different solutions. Saline and PBS, but not water, achieved high transfection
      efficiency. In addition, sucrose solution but not glucose solution resulted in
      high luciferase activity. CONCLUSIONS: Overall, angiogenesis might be enhanced by
      cotransfection of prostacyclin synthase gene or an increase in injection volume
      and osmotic pressure. These data provide important information for the clinical
      application of therapeutic angiogenesis to treat peripheral arterial disease.

PMID- 14568904
TI  - Opposing effects mediated by the chemokine receptor CXCR2 on myocardial ischemia
      reperfusion injury: recruitment of potentially damaging neutrophils and direct
      myocardial protection.
AB  - BACKGROUND: The timely reperfusion of ischemic myocardium limits infarction, but
      components of reperfusion, such as inflammation, may be injurious. The chemokine
      receptor CXCR2 mediates neutrophil chemotaxis. CXCR2 activation also inhibits
      hypoxia-induced death of isolated cardiac myocytes. This study assesses whether
      CXCR2 mediates protection in the intact heart and, if so, the magnitude of this
      protection relative to CXCR2-mediated chemotaxis of potentially damaging
      inflammatory cells. METHODS AND RESULTS: After ischemia-reperfusion in vivo,
      CXCR2-/- mice exhibited infarcts that were 50.5% smaller (P<0.05) with 44.3%
      fewer inflammatory cells (P<0.05) than wild type mice. These data suggest that in
      this model, CXCR2-mediated chemotaxis may be important in myocardial cell death.
      To isolate the role of CXCR2 specifically on blood cells, adoptive transfer
      experiments were performed. After ischemia-reperfusion, infarcts were 53.4%
      smaller (P<0.05) and contained 65.0% fewer inflammatory cells (P<0.05) in
      lethally irradiated wild type mice reconstituted with CXCR2-/- compared with wild
      type bone marrow. Thus, CXCR2 on blood cells is important in myocardial damage,
      most likely because of CXCR2-mediated chemotaxis. To unmask whether CXCR2
      mediates direct myocardial protection in the intact heart, wild type and CXCR2-/-
      hearts were studied in the absence of blood using Langendorff preparations. In
      this case, infarcts were 19.7% larger in CXCR2-/- than wild type hearts (P<0.05),
      revealing a novel CXCR2-mediated cardioprotective effect. CONCLUSIONS: CXCR2
      exerts opposing effects on myocardial viability during ischemia-reperfusion with
      recruitment of damaging inflammatory cells predominant over direct tissue
      protection.

PMID- 14568903
TI  - Evidence for a functional role of angiotensin II type 2 receptor in the cardiac
      hypertrophic process in vivo in the rat heart.
AB  - BACKGROUND: The precise function of angiotensin II type 2 receptor (AT2-R) in the
      mammalian heart in vivo is unknown. Here, we investigated the role of AT2-R in
      cardiac pressure overload. METHODS AND RESULTS: Rats were infused with vehicle,
      angiotensin II (Ang II), PD123319 (an AT2-R antagonist), or the combination of
      Ang II and PD123319 via subcutaneously implanted osmotic minipumps for 12 or 72
      hours. Ang II-induced increases in mean arterial pressure, left ventricular
      weight/body weight ratio, and elevation of skeletal alpha-actin and beta-myosin
      heavy chain mRNA levels were not altered by PD123319. In contrast, AT2-R blockade
      resulted in a marked increase in the gene expression of c-fos, endothelin-1, and
      insulin-like growth factor-1 in Ang II-induced hypertension. In parallel, Ang II
      stimulated mRNA and protein expression of atrial natriuretic peptide were
      significantly augmented by AT2-R blockade. Moreover, PD123319 markedly increased
      the synthesis of B-type natriuretic peptide. Furthermore, the expression of
      vascular endothelial growth factor and fibroblast growth factor-1 was
      downregulated by Ang II only in the presence of AT2-R blockade. CONCLUSIONS: Our
      results provide evidence that AT2-R plays a functional role in the cardiac
      hypertrophic process in vivo by selectively regulating the expression of growth
      promoting and growth-inhibiting factors.

PMID- 14568905
TI  - Anatomic stereotactic catheter ablation on three-dimensional magnetic resonance
      images in real time.
AB  - BACKGROUND: Targets for radiofrequency (RF) ablation of atrial fibrillation,
      atrial flutter, and nonidiopathic ventricular tachycardia are increasingly being
      selected on the basis of anatomic considerations. Because fluoroscopy provides
      only limited information about the relationship between catheter positions and
      cardiac structures and is associated with radiation risk, other approaches to
      mapping may be beneficial. METHODS AND RESULTS: An electromagnetic catheter
      positioning system was superimposed on 3D MR images using fiducial markers. This
      allowed the dynamic display of the catheter position on the true anatomy of
      previously acquired MR images in real time. In vitro accuracy and precision
      during catheter navigation were assessed in a phantom model and were 1.11+/-0.06
      and 0.30+/-0.07 mm (mean+/-SEM), respectively. Left and right heart
      catheterization was performed in 7 swine without the use of fluoroscopy, yielding
      an in vivo accuracy and precision of 2.74+/-0.52 and 1.97+/-0.44 mm,
      respectively. To assess the reproducibility of RF ablation, RF lesions were
      created repeatedly at the identical anatomic site in the right atrium (n=8
      swine). Average distance of the repeated right atrial ablations was 3.92+/-0.5
      mm. Straight 3-point lines were created in the right and left ventricles to
      determine the ability to facilitate complex ablation procedures (n=6 swine). The
      ventricular lesions deviated 1.70+/-0.24 mm from a straight line, and the point
      distance differed by 2.25+/-0.63 mm from the pathological specimen. CONCLUSIONS:
      Real-time display of the catheter position on 3D MRI allows accurate and precise
      RF ablation guided by the true anatomy. This may facilitate anatomically based
      ablation procedures in, for instance, atrial fibrillation or nonidiopathic
      ventricular tachycardia and decrease radiation times.

PMID- 14568906
TI  - Angiogenesis induced by endothelial nitric oxide synthase gene through vascular
      endothelial growth factor expression in a rat hindlimb ischemia model.
AB  - BACKGROUND: Because the mechanism of the angiogenic property of nitric oxide (NO)
      was not fully understood in vivo, we focused on the role of vascular endothelial
      growth factor (VEGF) in angiogenesis induced by endothelial NO synthase (eNOS)
      gene transfer. METHODS AND RESULTS: After intramuscular injection of eNOS DNA
      into a rat ischemic hindlimb, transfection of eNOS vector resulted in a
      significant increase in eNOS protein 1 week after transfection. In addition,
      tissue concentrations of nitrite and nitrate were significantly increased in rats
      transfected with the eNOS gene up to 2 weeks after transfection. The increase in
      tissue nitrite and nitrate concentrations was completely inhibited by NG-nitro-L
      arginine methyl ester (L-NAME). In contrast, serum concentrations of nitrite and
      nitrate and blood pressure were not changed by eNOS gene transfer. Importantly,
      overexpression of the eNOS gene resulted in a significant increase in peripheral
      blood flow, whereas L-NAME inhibited the increase in blood flow. Interestingly,
      basal blood flow was significantly lower in rats treated with L-NAME than in
      control rats. A significant increase in capillary number was consistently
      detected in rats transfected with the eNOS gene at 4 weeks after transfection,
      accompanied by a significant increase in VEGF. Moreover, administration of
      neutralizing anti-VEGF antibody abolished the increase in blood flow and
      capillary density induced by eNOS plasmid injection. CONCLUSIONS: Overall,
      intramuscular injection of bovine eNOS plasmid induced therapeutic angiogenesis
      in a rat ischemic hindlimb model, a potential therapy for peripheral arterial
      disease. The stimulation of angiogenesis by NO might be due to upregulation of
      local VEGF expression.

PMID- 14568907
TI  - Fatal hepatic necrosis following imatinib mesylate therapy.

PMID- 14568908
TI  - Serum concentration of cardiac Troponin T in patients with hypereosinophilic
      syndrome treated with imatinib is predictive of adverse outcomes.

PMID- 14568909
TI  - Epstein-Barr virus-associated B-cell non-Hodgkin lymphoma following treatment of
      hairy cell leukemia with cladribine.

PMID- 14568910
TI  - Reduced tumor load in peripheral blood after treatment with G-CSF and
      chemotherapy in children with tumors of the Ewing sarcoma family but not
      neuroblastoma.

PMID- 14568911
TI  - Subtyping of Fanconi anemia patients: implications for clinical management.

PMID- 14568912
TI  - Increased phosphorylation of a distinct subcellular pool of protein phosphatase,
      PP1gamma2, during epididymal sperm maturation.
AB  - The enzyme PP1gamma2 is a testis- and sperm-specific isoform of type 1 protein
      phosphatase (PP1), and it is the only isoform of PP1 in spermatozoa. The enzyme
      PP1gamma2 is essential for spermatogenesis and is also a key enzyme in the
      development and regulation of sperm motility. The carboxy terminus of the enzyme
      contains a consensus amino acid sequence for phosphorylation by cyclin-dependent
      kinases. Using antibodies specific to this phosphorylated amino acid sequence
      domain, we found that phosphorylated PP1gamma2 is present in bovine epididymal
      spermatozoa. The level of phosphorylated PP1gamma2 is significantly higher in
      motile caudal compared to immotile caput epididymal spermatozoa. A number of
      treatments, such as 2-chloro adenosine, cAMP analogues, cAMP phosphodiesterase
      inhibitors, and calcium, which stimulate sperm motility, did not alter the level
      of phosphorylated PP1gamma2. However, calyculin A, which is an inhibitor of
      protein phosphatase subtypes PP1 and PP2A, significantly increases the level of
      phosphorylated PP1gamma2 in both caput and caudal epididymal spermatozoa. Partial
      purification by column chromatography showed that phosphorylated PP1gamma2 is
      catalytically active. Phosphorylated PP1gamma2 is the only spontaneously
      catalytically active form of the enzyme in caudal sperm extracts. Western blot
      analysis shows that the enzyme cyclin-dependent kinase 2, one of the enzymes that
      phosphorylates the consensus domain at the carboxy terminus in PP1 isoforms, is
      present in spermatozoa. Western blot analysis of proteins extracted from purified
      head and tail fragments of spermatozoa showed that phosphorylated PP1gamma2 is
      present predominantly in the sperm head. Fluorescence immunocytochemistry also
      showed that phosphorylated PP1gamma2 is present predominantly in the posterior
      region of the sperm head. The distinct subcellular localization and changes in
      its level during sperm maturation suggest a possible role for sperm
      phosphorylated PP1gamma2 in signaling events during fertilization.

PMID- 14568913
TI  - Role of intracellular cyclic adenosine 3',5'-monophosphate concentration and
      oocyte-cumulus cells communications on the acquisition of the developmental
      competence during in vitro maturation of bovine oocyte.
AB  - The present study was designed to address the physiological role played by cAMP
      on gap junction (GJ) mediated communications between oocyte and cumulus cells
      during in vitro maturation. Cyclic AMP was stimulated by different collection and
      maturation media known to induce different rates of nuclear maturation and
      developmental competence as well as different levels of cumulus expansion.
      Cumulus-oocyte complexes (COCs) were matured for 0, 3, 7, 12, 18, and 24 h in the
      absence of stimulation or in the presence of serum and gonadotropins (fetal
      bovine serum+human menopausal gonadotropins [FCS+hMG]) or 0.01 microg/ml of
      invasive adenylate cyclase (iAC). For each time point, intracellular cAMP
      concentration ([cAMP]i) was determined either in the whole COC or oocyte after
      cumulus cell removal. GJ functional status was analyzed by microinjection of
      Lucifer yellow fluorescent dye in cumulus-enclosed oocytes and by
      immunohistochemical localization of connexin 43 (Cx43). In the absence of
      stimulation, [cAMP]i in COC and oocyte was lower than in other groups, and
      communications declined after 3 h of culture. In the FCS+hMG group, [cAMP]i
      increased significantly in COC, with a peak between 3 and 7 h that was temporally
      correlated with the beginning of the cumulus expansion process, which occurred
      only in this group and with the termination of the communications. COC matured in
      the presence of iAC showed a moderate increase of [cAMP]i during all of the
      maturation times as well as a prolongation of oocyte-cumulus cell communications.
      The immunohistochemical localization of Cx43 confirmed the delay in connexons
      protein turnover in iAC-treated COCs. Our results show that cumulus expansion and
      oocyte developmental competence are induced by different levels of cAMP and that
      its intracellular concentration may affect cell coupling between oocyte and
      cumulus cells. We hypothesize that the higher developmental competence of COCs
      matured in the presence of iAC could be achieved through a moderate increase of
      intracellular cAMP, which in turn determines a prolongation of communications
      between the two cell types.

PMID- 14568914
TI  - Steroidal regulation of uterine edema and tissue inhibitors of metalloproteinase
      (TIMP)-3 messenger RNA expression is altered in TIMP-1-deficient mice.
AB  - Tissue inhibitors of metalloproteinases (TIMPs) are expressed within the uteri of
      virtually all species where they are postulated to control extracellular matrix
      turnover, cellular apoptosis, and proliferation. The objective of the current
      study was to examine the steroidal regulation of uterine TIMP expression and to
      determine the potential role of the TIMP-1 gene product in this regulation. To
      accomplish these goals, ovariectomized female TIMP-1 wild-type and null mice were
      treated with estradiol, progesterone, or estradiol and progesterone and killed at
      various times after steroid administration. Estradiol induced a significant
      reduction in uterine TIMP-3 expression in wild-type mice at 8 and 24 h post
      steroid administration, but the ability of this steroid to decrease TIMP-3
      expression was impaired in the uteri of TIMP-1 null mice. Further, estrogen
      induced uterine wet-weight gain/edema was enhanced in the TIMP-1 null mice, and
      the antiestrogen compound ICI 182780 or progesterone could only partially block
      this estrogenic effect. It is concluded from this study that steroidal modulation
      of uterine TIMP-3 expression and regulation of wet-weight gain/edema are altered
      in TIMP-1 null mice. These observations suggest that steroids induce uterine TIMP
      1 expression and, in turn, that TIMP-1 influences TIMP-3 mRNA expression and
      uterine edema.

PMID- 14568915
TI  - Bovine cumulus cell-oocyte gap junctional communication during in vitro
      maturation in response to manipulation of cell-specific cyclic adenosine 3',5'
      monophosophate levels.
AB  - In the growing follicle, communication between the oocyte and its surrounding
      follicular cells is essential for normal oocyte and follicular development.
      Maturation of the fully grown oocyte in vivo is associated with the loss of
      cumulus cell-oocyte gap junctional communication, preventing entry of meiotic
      modulating factors such as cAMP into the oocyte. We have previously shown that
      oocyte and cumulus cell cAMP levels can be independently regulated using
      inhibitors of cell-specific phosphodiesterase (PDE) isoenzymes. The objectives of
      this study were to examine the effects of cell type-specific PDE inhibitors on
      the maintenance of cumulus cell-oocyte gap junction communication (GJC) and
      oocyte meiotic progression. Cumulus-oocyte complexes (COCs) were aspirated from
      antral follicles of abattoir-derived ovaries. Cumulus cell-oocyte GJC during
      oocyte maturation was quantified using the fluorescent dye, calcein-AM. COCs were
      cultured in the presence of specific PDE inhibitors, milrinone (an oocyte PDE3
      inhibitor) or rolipram (a cumulus cell PDE4 inhibitor), and were pulsed with
      calcein-AM to allow dye transfer between the two cell types. Following cumulus
      cell removal, fluorescence in denuded oocytes was measured by microphotometry,
      and meiotic progression was assessed. In control COCs, dye transfer from cumulus
      cells to the oocyte fell progressively from 0 to 9 h, after which oocyte-cumulus
      cell GJC was completely lost. Loss of GJC was significantly attenuated (P < 0.05)
      during this time in response to treatment with milrinone and rolipram. Forskolin
      maintained GJC at the initial 0 h level until 3-4 h of culture, whereas treatment
      with milrinone and forskolin together actually increased the level of dye
      transfer above that in COCs treated with forskolin alone. Importantly, all
      treatments that prolonged GJC also delayed meiotic resumption, with meiosis
      generally resuming when fluorescence had fallen to approximately 40% of initial
      levels. These results, together with our previous studies, demonstrate that
      treatments that maintain or elevate cAMP levels in cumulus cells, oocytes, or
      both result in prolonged oocyte-cumulus cell communication and delayed meiotic
      resumption.

PMID- 14568916
TI  - Gene expression profiling of differentially expressed genes in granulosa cells of
      bovine dominant follicles using suppression subtractive hybridization.
AB  - Development of antral follicles beyond 3 to 4 mm in cattle appears as a wave
      pattern that occurs two to three times during the estrous cycle. Each wave
      presents a cyclic recruitment of multiple follicles at the 3- to 4-mm stage,
      followed by the selection of a single follicle that becomes the dominant follicle
      (DF). The molecular determinants involved in the follicular dominance process
      remain poorly understood. The objective of the current study was to compare gene
      expression in granulosa cells (GCs) between growing dominant follicles from Day 5
      of the estrous cycle and nonselected small follicles (<or=4 mm) using the
      suppression subtractive hybridization (SSH) approach to identify candidate genes
      differentially expressed in GCs of the DF. Small follicle cDNAs were subtracted
      from DF cDNAs (DF-SF) and used to establish a DF GC-subtracted cDNA library. A
      total of 42 nonredundant cDNAs were identified. Detection of previously
      identified genes such as CX43, CYP19, INHBA, and SERPINE2 supported the validity
      of our experimental model and the use of SSH as the method of analysis. For
      selected genes such as ApoER2, CPD, CSPG2, 14-3-3 epsilon, NR5A2/SF2, RGN/SMP30,
      and SERPINE2, gene expression profiles were compared by virtual Northern blot or
      reverse transcriptase-polymerase chain reaction, and results confirmed an
      increase or induction of their mRNA in GCs of dominant follicles compared with
      that of small follicles. We conclude that we have identified novel genes (known
      and unknown) that are up-regulated in bovine GCs that may affect follicular
      growth, dominance, or both.

PMID- 14568917
TI  - Search for the bovine homolog of the murine ped gene and characterization of its
      messenger RNA expression during bovine preimplantation development.
AB  - In mice, a gene (Ped: preimplantation embryo development) that regulates
      preimplantation embryonic growth, including cleavage rate and embryo
      survivability, has been described. The objective of the current study was to
      identify the bovine homolog of the Ped gene and to characterize the mRNA
      expression pattern of this gene during bovine preimplantation embryo development.
      The NCBI GenBank/EBI expressed sequence tags (EST) databases were searched for
      bovine ESTs that were homologous to the murine Ped gene, and the resulting ESTs
      were aligned and assembled into a contiguous sequence. The homology of the
      sequence to the murine Ped gene was confirmed. Primers were designed for the
      sequence, and the mRNA expression pattern was characterized during bovine
      preimplantation embryo development in vivo and in vitro. In vitro-produced bovine
      zygotes were cultured either in vitro, in synthetic oviduct fluid, or in vivo in
      the ewe oviduct for 1-7 days and processed for quantitative real-time polymerase
      chain reaction (PCR). Transcript abundance increased at each stage of
      development. However, the expression levels were consistently higher in in vivo
      cultured embryos at all stages, with in vivo-cultured embryos showing a 9-fold
      increase in relative transcript abundance during culture from the zygote to the
      blastocyst stage in contrast to just under a 4-fold increase during the same
      culture period in vitro. The mRNA expression pattern of the gene was investigated
      in early- and late-cleaving two-cell embryos collected at 25, 28, 32, and >or=36
      h postinsemination (pi). Transcript relative abundance was highest in those
      embryos that had cleaved by 28 hpi and decreased almost 3-fold thereafter. In
      conclusion, we have identified a potential bovine homolog of the murine Ped gene.
      We have characterized the mRNA expression pattern of this gene during
      preimplantation embryo development in cattle and shown that a greater relative
      abundance of the gene transcript is associated with embryos of higher quality (in
      vivo cultured) and greater developmental potential (early cleaving).

PMID- 14568918
TI  - Expression of vasoactive intestinal peptide receptor messenger RNA in the
      hypothalamus and pituitary throughout the turkey reproductive cycle.
AB  - Vasoactive intestinal peptide (VIP) has been implicated in the regulation of
      avian reproductive activity and appears to act at the level of the hypothalamus
      and pituitary. This in situ hybridization histochemistry study describes the
      distribution of VIP receptor mRNA expression in the hypothalamus and the
      pituitary of reproductively active (laying) and quiescent (nonphotostimulated,
      incubating, and photorefractory) female turkeys and characterizes the differences
      observed in VIP receptor gene expression. VIP receptor mRNA, while expressed
      throughout the hypothalamus, was specifically expressed in areas known to contain
      GnRH-I neurons in the chicken, i.e., the lateral septum, medial preoptic area,
      anterior hypothalamus, and paraventricular nucleus. Significant differences in
      VIP receptor mRNA expression between different reproductive states was observed
      only within the infundibular nuclear complex. VIP receptor mRNA was markedly less
      in nonphotostimulated and photorefractory hens as compared with laying and
      incubating hens. The most dense VIP receptor mRNA was found in the anterior
      pituitary, where it was 2.4- and 3.0-fold greater in laying and incubating hens,
      respectively, as compared with that in nonphotostimulated ones. Hens that stopped
      incubating and became photorefractory displayed pituitary VIP receptor mRNA
      levels similar to those of nonphotostimulated birds. The changes in pituitary VIP
      receptor mRNA expression were positively correlated with known changes in
      pituitary prolactin (PRL) mRNA expression and PRL content and release. These
      findings indicate that the variations in PRL secretion observed across the turkey
      reproductive cycle are, in part, regulated by changes in VIP receptors at the
      pituitary level.

PMID- 14568919
TI  - Virus evasion of MHC class I molecule presentation.

PMID- 14568920
TI  - Cutting edge: dendritic cell actin cytoskeletal polarization during immunological
      synapse formation is highly antigen-dependent.
AB  - Dendritic cells (DC) actively rearrange their actin cytoskeleton to participate
      in formation of the immunological synapse (IS). In this study, we evaluated the
      requirements for DC participation in the IS. DC rearrange their actin
      cytoskeleton toward naive CD4(+) T cells only in the presence of specific MHC
      peptide complexes. In contrast, naive CD4(+) T cells polarized their cytoskeletal
      proteins in the absence of Ag. DC cytoskeletal rearrangement occurred at the same
      threshold of peptide-MHC complexes as that required for T cell activation.
      Furthermore, T cell activation was inhibited by specific blockade of DC
      cytoskeletal rearrangement. When TCR-MHC interaction was bypassed by using Con A
      activated T cells, DC polarization was abrogated. In addition, directional
      ligation of MHC class II resulted in DC cytoskeletal polarization. Our findings
      suggest that a high Ag specificity is required for DC IS formation and that MHC
      class II signaling plays a central role in this process.

PMID- 14568921
TI  - Role of IL-12 receptor beta 1 in regulation of T cell response by APC in
      experimental autoimmune encephalomyelitis.
AB  - IL-12 was thought to be involved in the development of experimental autoimmune
      encephalomyelitis (EAE), a Th1 cell-mediated autoimmune disorder of the CNS.
      However, we have recently found that IL-12 responsiveness, via IL-12Rbeta2, is
      not required in the induction of EAE. To determine the role of IL-12Rbeta1, a key
      subunit for the responsiveness to both IL-12 and IL-23, in the development of
      autoimmune diseases, we studied EAE in mice deficient in this subunit of IL-12R.
      IL-12Rbeta1(-/-) mice are completely resistant to myelin oligodendrocyte
      glycoprotein (MOG)-induced EAE, with an autoantigen-specific Th2 response. To
      study the mechanism underlying this Th2 bias, we cocultured purified CD4(+) T
      cells and APCs of MOG-immunized mice. We demonstrate that IL-12Rbeta1(-/-) APCs
      drive CD4(+) T cells of both wild-type and IL-12Rbeta1(-/-) mice to an Ag-induced
      Th2 phenotype, whereas wild-type APCs drive these CD4(+) T cells toward a Th1
      type. IL-12Rbeta1(-/-) CD4(+) T cells, in turn, appear to exert an
      immunoregulatory effect on the capacity of wild-type APCs to produce IFN-gamma
      and TNF-alpha. Furthermore, decreased levels of IL-12p40, p35, and IL-23p19 mRNA
      expression were found in IL-12Rbeta1(-/-) APCs, indicating an autocrine pathway
      of IL-12/IL-23 via IL-12Rbeta1. IL-18 production and IL-18Ralpha expression are
      also significantly decreased in IL-12Rbeta1(-/-) mice immunized with MOG. We
      conclude that in the absence of IL-12Rbeta1, APCs play a prominent regulatory
      role in the induction of autoantigen-specific Th2 cells.

PMID- 14568923
TI  - Expression of activated Notch3 in transgenic mice enhances generation of T
      regulatory cells and protects against experimental autoimmune diabetes.
AB  - Thymic-derived dysregulated tolerance has been suggested to occur in type 1
      diabetes via impaired generation of CD4(+)CD25(+) T regulatory cells, leading to
      autoimmune beta cell destruction. In this study, we demonstrate that Notch3
      expression is a characteristic feature of CD4(+)CD25(+) cells. Furthermore,
      streptozotocin-induced autoimmune diabetes fails to develop in transgenic mice
      carrying the constitutively active intracellular domain of Notch3 in thymocytes
      and T cells. The failure to develop the disease is associated with an increase of
      CD4(+)CD25(+) T regulatory cells, accumulating in lymphoid organs, in pancreas
      infiltrates and paralleled by increased expression of IL-4 and IL-10.
      Accordingly, CD4(+) T cells from Notch3-transgenic mice inhibit the development
      of hyperglycemia and insulitis when injected into streptozotocin-treated wild
      type mice and display in vitro suppressive activity. These observations,
      therefore, suggest that Notch3-mediated events regulate the expansion and
      function of T regulatory cells, leading to protection from experimental
      autoimmune diabetes and identify the Notch pathway as a potential target for
      therapeutic intervention in type 1 diabetes.

PMID- 14568924
TI  - Thymocyte sensitivity and supramolecular activation cluster formation are
      developmentally regulated: a partial role for sialylation.
AB  - TCR reactivity is tuned during thymic development. Immature thymocytes respond to
      low-affinity self-ligands resulting in positive selection. Following
      differentiation, T cells no longer respond to low-affinity ligands, but respond
      well to high-affinity (foreign) ligands. We show in this study that this response
      includes integrin activation, supramolecular activation cluster formation, Ca(2+)
      flux, and CD69 expression. Because glycosylation patterns are known to change
      during T cell development, we tested whether alterations in sialylation influence
      CD8 T cell sensitivity to low affinity TCR ligands. Using neuraminidase treatment
      or genetic deficiency in the ST3Gal-I sialyltransferase, we show that
      desialylation of mature CD8 T cells enhances their sensitivity to low-affinity
      ligands, although these treatments do not completely recapitulate the dynamic
      range of immature T cells. These studies identify sialylation as one of the
      factors that regulate CD8 T cell tuning during development.

PMID- 14568922
TI  - Interplay between TCR affinity and necessity of coreceptor ligation: high
      affinity peptide-MHC/TCR interaction overcomes lack of CD8 engagement.
AB  - CD8 engagement is believed to be a critical event in the activation of naive T
      cells. In this communication, we address the effects of peptide-MHC (pMHC)/TCR
      affinity on the necessity of CD8 engagement in T cell activation of primary naive
      cells. Using two peptides with different measured avidities for the same pMHC-TCR
      complex, we compared biochemical affinity of pMHC/TCR and the cell surface
      binding avidity of pMHC/TCR with and without CD8 engagement. We compared early
      signaling events and later functional activity of naive T cells in the same
      manner. Although early signaling events are altered, we find that high-affinity
      pMHC/TCR interactions can overcome the need for CD8 engagement for proliferation
      and CTL function. An integrated signal over time allows T cell activation with a
      high-affinity ligand in the absence of CD8 engagement.

PMID- 14568925
TI  - Critical role for CXCR4 signaling in progenitor localization and T cell
      differentiation in the postnatal thymus.
AB  - T cell differentiation in the thymus depends on sequential interactions between
      lymphoid progenitors and stromal cells in discrete regions of the cortex. Here we
      show that CXCL12/CXCR4 signaling is absolutely required for proper localization
      of early progenitors into the cortex and thus for successful steady state
      differentiation. All early progenitors in the thymus express CXCR4, and its
      ligand (CXCL12) is expressed only by stromal cells in the cortex, where early
      progenitors are found. Early progenitors migrate in response to CXCL12 in vitro,
      while thymus-specific deletion of CXCR4 in vivo results in failed cortical
      localization and developmental arrest. These findings indicate a crucial and
      nonredundant role for CXCR4 in facilitating localization of early lymphoid
      progenitors to tissue regions of the thymus, where lineage commitment and
      proliferation are controlled.

PMID- 14568926
TI  - CD8+ alpha beta+ T cells that lack surface CD5 antigen expression are a major
      lymphotactin (XCL1) source in peripheral blood lymphocytes.
AB  - To better characterize the cellular source of lymphotactin (XCL1), we compared
      XCL1 expression in different lymphocyte subsets by real-time PCR. XCL1 was
      constitutively expressed in both PBMC and CD4(+) cells, but its expression was
      almost 2 log higher in CD8(+) cells. In vitro activation was associated with a
      substantial increase in XCL1 expression in both PBMC and CD8(+) cells, but not in
      CD4(+) lymphocytes. The preferential expression of XCL1 in CD8(+) cells was
      confirmed by measuring XCL1 production in culture supernatants, and a good
      correlation was found between figures obtained by real-time PCR and XCL1
      contents. XCL1 expression was mostly confined to a CD3(+)CD8(+) subset not
      expressing CD5, where XCL1 expression equaled that shown by gammadelta(+) T
      cells. Compared with the CD5(+) counterpart, CD3(+)CD8(+)CD5(-) cells, which did
      not express CD5 following in vitro activation, showed preferential expression of
      the alphaalpha form of CD8 and a lower expression of molecules associated with a
      noncommitted/naive phenotype, such as CD62L. CD3(+)CD8(+)CD5(-) cells also
      expressed higher levels of the XCL1 receptor; in addition, although not differing
      from CD3(+)CD8(+)CD5(+) cells in terms of the expression of most alpha- and beta
      chemokines, they showed higher expression of CCL3/macrophage inflammatory protein
      1alpha. These data show that TCR alphabeta-expressing lymphocytes that lack CD5
      expression are a major XCL1 source, and that the contribution to its synthesis by
      different TCR alphabeta-expressing T cell subsets, namely CD4(+) lymphocytes, is
      negligible. In addition, they point to the CD3(+)CD8(+)CD5(-) population as a
      particular T cell subset within the CD8(+) compartment, whose functional
      properties deserve further attention.

PMID- 14568927
TI  - Another view of T cell antigen recognition: cooperative engagement of glycolipid
      antigens by Va14Ja18 natural T(iNKT) cell receptor [corrected].
AB  - Va14Ja18 natural T (iNKT) cells rapidly elicit a robust effector response to
      different glycolipid Ags, with distinct functional outcomes. Biochemical
      parameters controlling iNKT cell function are partly defined. However, the impact
      of iNKT cell receptor beta-chain repertoire and how alpha-galactosylceramide
      (alpha-GalCer) analogues induce distinct functional responses have remained
      elusive. Using altered glycolipid ligands, we discovered that the Vb repertoire
      of iNKT cells impacts recognition and Ag avidity, and that stimulation with
      suboptimal avidity Ag results in preferential expansion of high-affinity iNKT
      cells. iNKT cell proliferation and cytokine secretion, which correlate with iNKT
      cell receptor down-regulation, are induced within narrow biochemical thresholds.
      Multimers of CD1d1-alphaGalCer- and alphaGalCer analogue-loaded complexes
      demonstrate cooperative engagement of the Va14Ja18 iNKT cell receptor whose
      structure and/or organization appear distinct from conventional alphabeta TCR.
      Our findings demonstrate that iNKT cell functions are controlled by affinity
      thresholds for glycolipid Ags and reveal a novel property of their Ag receptor
      apparatus that may have an important role in iNKT cell activation.

PMID- 14568928
TI  - Cross-linking of the mannose receptor on monocyte-derived dendritic cells
      activates an anti-inflammatory immunosuppressive program.
AB  - Immature monocyte-derived dendritic cells (DC) strongly express the endocytic
      mannose receptor (MR). Addition of a specific anti-MR mAb (clone PAM-1) for 24 h
      to cultures of immature DC induced phenotypical and functional maturation of the
      cells, assessed as up-regulation of costimulatory molecules and CD83, and
      chemotactic response to CCL19. A different isotype-matched anti-MR mAb (clone
      19.2) had no significant effect. Engagement of MR with mAb PAM-1 induced the
      production of the anti-inflammatory cytokines IL-10, IL-1R antagonist, and of the
      nonsignaling IL-1R type II. In contrast IL-1beta, TNF, and IL-12 were not
      produced. PAM-1-treated DC were unable to polarize Th1 effector cells and did not
      secrete the chemokines CXCL10 and CCL19; in turn, they produced large amounts of
      CCL22 and CCL17, thus favoring the amplification of Th2 circuits. T cells
      cocultured with PAM-1-matured DC initially proliferated but later became anergic
      and behaved as suppressor/regulatory cells. Natural ligands binding to MR had
      differential effects. MUC III (a partially purified mucin), biglycan (a purified
      complex proteoglycan), and mannosylated lipoarabinomannan from Mycobacterium
      tuberculosis affected cytokine production with high IL-10, IL-1R antagonist, IL
      1R type II, and inhibition of IL-12. In contrast, mannan, dextran, and
      thyroglobulin had no significant effect. In conclusion, the appropriate
      engagement of the MR by mAb PAM-1 and selected natural ligands elicit a secretory
      program in mono-derived DC characterized by a distinct profile of
      cytokines/chemokines with the ability to dampen inflammation and to inhibit the
      generation of Th1-polarized immune responses.

PMID- 14568929
TI  - Translational control of inducible nitric oxide synthase by IL-13 and arginine
      availability in inflammatory macrophages.
AB  - Inducible NO synthase (iNOS) and its generation of NO from L-arginine are subject
      to transcriptional as well as posttranscriptional control by cytokines. In this
      study, we describe a novel, translational mechanism of iNOS regulation by
      arginine availability. Using mouse inflammatory peritoneal macrophages stimulated
      with IFN-gamma plus LPS, we demonstrate that the suppression of iNOS protein,
      which is observed after a 16-h (but not after a 6-h) pretreatment with IL-13,
      despite an unaltered iNOS mRNA level, results from arginine depletion by
      arginase. The addition of arginase inhibitors (in the pretreatment phase) or of
      arginine (in the stimulation phase) completely blocked the down-regulation of
      iNOS protein by IL-13. The rescuing effect of arginine supplementation was not
      due to a positive feedback regulation of iNOS expression via enhanced production
      of NO. A striking suppression of iNOS protein (but not of iNOS mRNA) was also
      seen, when IL-13 was replaced by purified arginase or when macrophages were
      stimulated with IFN-gamma/LPS in arginine-free medium. Arginine deficiency
      specifically impaired the de novo synthesis and the stability of iNOS protein,
      but did not affect the production of TNF and the overall protein synthesis of the
      macrophages. From these results, we conclude that arginine not only functions as
      a substrate for iNOS, but is also critical for maintaining normal levels of iNOS
      protein in cytokine-stimulated macrophages.

PMID- 14568930
TI  - Dectin-1 expression and function are enhanced on alternatively activated and GM
      CSF-treated macrophages and are negatively regulated by IL-10, dexamethasone, and
      lipopolysaccharide.
AB  - Dectin-1 is the major macrophage receptor for beta-glucans and generates a
      proinflammatory response through the recognition of these carbohydrates on fungal
      pathogens. We have examined the effects of cytokines and other agents on the
      expression and functions of dectin-1 in both resident and elicited murine
      peritoneal macrophages (Mphi). Dectin-1 expression was found to be highly up
      regulated by GM-CSF and by the cytokines that induce alternative macrophage
      activation, IL-4 and IL-13. In contrast, IL-10, LPS, and dexamethasone, but not
      IFN-gamma, down-regulated the expression of this receptor. Modulation of dectin-1
      receptor levels correlated with the ability of these macrophages to bind zymosan
      and significantly affected the contribution of this receptor to the resultant
      proinflammatory response, as measured by the production of TNF-alpha, although
      some Mphi-specific differences were observed. These results correlate with the
      known effects of these cytokines and other agents on the ability of the immune
      system to recognize and respond to fungal pathogens.

PMID- 14568931
TI  - Absence of programmed death receptor 1 alters thymic development and enhances
      generation of CD4/CD8 double-negative TCR-transgenic T cells.
AB  - Programmed death receptor 1 (PD-1) is expressed on thymocytes in addition to
      activated lymphocyte cells. Its ligation is thought to negatively regulate T cell
      activation, and PD-1(-/-) mice develop autoimmunity. To study the role of PD-1 on
      the development and function of a monoclonal CD8(+) T cell population, 2C TCR
      transgenic/recombination-activating gene 2(-/-)/PD-1(-/-) mice were generated.
      Unexpectedly, approximately 30% of peripheral T cells in these mice were CD4/CD8
      double negative (DN). Although the DN cells were not activated by Ag-expressing
      APCs, they functioned normally in response to anti-CD3/anti-CD28. These cells had
      a naive surface phenotype and lacked expression of NK1.1, B220, and gammadelta
      TCR; and the majority did not up-regulate CD8alphaalpha expression upon
      activation, arguing that they are not predominantly diverted gammadelta-lineage
      cells. The thymus was studied in detail to infer the mechanism of generation of
      DN peripheral T cells. Total thymus cellularity was reduced in 2C TCR
      transgenic/recombination-activating gene 2(-/-)/PD-1(-/-) mice, and a relative
      increase in DN cells and decrease in double-positive (DP) cells were observed.
      Increased annexin V(+) cells among the DP population argued for augmented
      negative selection in PD-1(-/-) mice. In addition, an increased fraction of the
      DN thymocytes was HSA negative, suggesting that they had undergone positive
      selection. This possibility was supported by decreased emergence of DN PD-1(-/-)
      2C cells in H-2(k) bone marrow chimera recipients. Our results are consistent
      with a model in which absence of PD-1 leads to greater negative selection of
      strongly interacting DP cells as well as increased emergence of DN alphabeta
      peripheral T cells.

PMID- 14568932
TI  - Cell proliferation arrest within intrathymic lymphocyte progenitor cells causes
      thymic atrophy mediated by the aryl hydrocarbon receptor.
AB  - Activation of the aryl hydrocarbon receptor (AHR), a basic helix-loop-helix
      transcription factor, in lymphocytes by the immunosuppressive environmental
      contaminant 2,3,7,8,-tetrachlorodibenzo-p-dioxin (TCDD) has been shown to cause
      thymic atrophy in every species studied. We set out to identify the specific
      hemopoietic cellular populations in which the AHR was activated to lead to thymic
      atrophy and to determine the effect of AHR activation in those cellular
      populations. Initially, we examined whether AHR activation in intrathymic
      dendritic cells could mediate TCDD-induced thymic atrophy. It was found that
      thymic atrophy occurred only when the AHR could be activated in the thymocytes
      but not hemopoietic-derived dendritic cells or other APCs. We next analyzed the
      effect of TCDD on the proliferation of thymocytes in vivo. There was a
      significant increase in the percentage of thymocytes in the G(1) phase of the
      cell cycle and a significant decrease in the percentage of S plus G(2)/M
      thymocytes, especially in the CD4(-)CD8(-)CD3(-) triple-negative intrathymic
      progenitor cell population 24 h after exposure to 30 micro g/kg TCDD.
      Furthermore, by 12 h after exposure to TCDD, we observed approximately 60%
      reduction of 5-bromo-2'-deoxyuridine incorporation in specific intrathymic
      progenitor cell populations. This reduction persisted for at least 6 days. These
      data indicate that intrathymic progenitor cells are direct targets of TCDD in the
      thymus and suggest that TCDD causes thymic atrophy by reducing entrance into cell
      cycle in these populations.

PMID- 14568933
TI  - Early events in peripheral regulatory T cell induction via the nasal mucosa.
AB  - Nasal application of soluble Ags leads to Ag-specific suppression of systemic
      immune responses. This tolerance can be transferred to naive mice by CD4(+)
      regulatory T cells (T(R) cells) from the spleen, but little is known about the
      induction of mucosal T(R) cells in vivo. To investigate the induction of T(R)
      cells in the nose-draining cervical lymph node (CLN), CD4(+) T cells from DO11.10
      OVA TCR transgenic mice were transferred to BALB/c recipients. Within 48 h after
      nasal OVA application, CD4(+) DO11.10 T cells in CLN, but not in the peripheral
      lymph node, had divided. Similarly, nonmucosal (i.m.) OVA application also
      induced CD4(+) DO11.10 T cells to proliferate in the draining inguinal lymph node
      (ILN), yet more vigorously and with different kinetics than the CD4(+) DO11.10 T
      cells in CLN. Functional analysis revealed that only proliferating CD4(+) DO11.10
      T cells from CLN, and not ILN, could transfer tolerance to naive recipients.
      CD4(+) DO11.10 T cells from CLN were phenotypically similar to CD4(+) DO11.10 T
      cells from ILN, however, in CLN a higher percentage of CD25(+) proliferating
      CD4(+) DO11.10 T cells were detected compared with ILN. CD25 is not a
      discriminative marker for mucosal T(R) cells because both CD25(+) and CD25(-)
      CD4(+) DO11.10 T cells from the CLN could suppress delayed type hypersensitivity
      responses in adoptive transfer. These findings demonstrate that although striking
      similarities exist between the differentiation of T(R) and effector T cells, this
      does not include their function. We are the first to demonstrate that functional
      T(R) cells, which reside within both CD25(+) and CD25(-) subsets, can be isolated
      from CLN as early as 3 days after nasal OVA application.

PMID- 14568934
TI  - CD4+CD25+ T cells lyse antigen-presenting B cells by Fas-Fas ligand interaction
      in an epitope-specific manner.
AB  - Suppression by regulatory T cells is now acknowledged to play a key role in the
      down-regulation of T cell responses to foreign and self Ags. In addition to the
      naturally occurring CD4(+)CD25(+) population, several subtypes of induced
      regulatory cells have been reported, but their mechanisms of action remain
      unclear. Conversely, cytotoxic CD4(+) cells that lyse cells presenting their
      cognate peptide have been described, but their potential role in immunoregulation
      remains to be delineated. A CD4(+) T cell line derived from BALB/c mice immunized
      with peptide 21-35, containing a major T cell epitope of a common allergen,
      Dermatophagoides pteronyssinus group 2 allergen, was found to lyse the Ag
      presenting WEHI cell line via Fas-Fas ligand and only in the presence of the
      cognate peptide. Cytolytic activity was likewise shown for other T cell lines and
      occurred even after a single cycle of in vitro stimulation. Moreover, T cells
      that efficiently lysed WEHI cells were unresponsive to stimulation with their
      cognate Ag and were dependent on IL-2 for growth and survival, which was
      reflected in a constitutive expression of CD25 independently of activation
      status. Proliferating B cells were also killed by the CTLs. By lysing Ag
      presenting B cells in an epitope-specific manner, the nonproliferating CTLs were
      shown to down-regulate the proliferation of bystander T cells. These data
      demonstrate that cytotoxic CD4(+)CD25(+) T cells that lack proliferation
      capacities have the potential to down-regulate an immune response by killing Ag
      presenting B cells. This could represent an important and specific down
      regulatory mechanism of secondary immune responses in vivo.

PMID- 14568935
TI  - A murine locus on chromosome 18 controls NKT cell homeostasis and Th cell
      differentiation.
AB  - Th cell differentiation is a critical event in the adaptive immune response.
      C57BL strains develop predominant Th1 responses while BALB/c develops a
      predominant Th2 response. To identify quantitative trait loci controlling this
      variation, we performed Th1/Th2 differentiation assays of F(1) x BALB/c progeny.
      A single strong quantitative trait locus was identified on chromosome 18, with
      weaker effects detectable on chromosomes 5, 12, and 14. By preparing a congenic
      BALB.B10.D2c18 strain, we were able to demonstrate that this single locus was
      sufficient to "repolarize" spleen cell cultures. This difference was not due to
      intrinsic differences in CD4(+) T cells. Rather, introgression of the chromosome
      18 locus into BALB/c disrupted Va14Ja18 NKT cell homeostasis resulting in the
      almost complete absence of this T cell subset. Taken together, these data
      indicate that genes within chromosome 18 control strain-dependent development of
      Va14Ja18 NKT cells.

PMID- 14568936
TI  - CD40 stimulation of human peripheral B lymphocytes: distinct response from naive
      and memory cells.
AB  - During secondary immune response, memory B lymphocytes proliferate and
      differentiate into Ig-secreting cells. In mice, the binding of CD40 by CD154
      clearly enhances the activation and differentiation of memory B lymphocytes. In
      humans, the role of CD40-CD154 in the stimulation of memory B lymphocytes is not
      as obvious since in vitro studies reported positive and negative effects on their
      proliferation and differentiation in Ig-secreting cells. In this study, we
      examine the response of peripheral memory and naive cells in relation to the
      duration of CD40-CD154 interaction. We measured the proliferation and
      differentiation of both subsets stimulated with CD154 and IL-4 for short- (4-5
      days) and long-term (>7 days) periods. Following short-term stimulation, memory B
      lymphocytes did not expand but represented the only subset differentiating into
      IgG- and IgM-secreting cells. A longer stimulation of this population led to cell
      death, while promoting naive B lymphocyte proliferation, expansion, and
      differentiation into IgM- or IgG-secreting cells. This prolonged CD40 stimulation
      also triggered naive B lymphocytes to switch to IgG and to express CD27 even in
      absence of somatic hypermutation, suggesting that these latter events could be
      independent. This study suggests that naive and memory B lymphocytes have
      distinct requirements to engage an immune response, reflecting their different
      roles in humoral immunity.

PMID- 14568937
TI  - Ly49D receptor expressed on immature B cells regulates their IFN-gamma secretion,
      actin polymerization, and homing.
AB  - Low levels of IFN-gamma secreted by immature B cells prevent their own migration
      and homing to the lymph nodes and premature encounter with Ag. In this study we
      followed the mechanism regulating IFN-gamma secretion by immature B cells. We
      show that the MHC class I receptor, Ly49D, is expressed on immature B cells and
      is down-regulated during maturation. Activation of this receptor leads to
      increase in IFN-gamma transcription and translation and results in the altered
      ability of B cells to polymerize actin in response to chemokine stimulation.
      Moreover, we show that H2-D blockage inhibits the ability of immature B cells to
      transcribe the IFN-gamma gene and results in rescue of cytoskeletal
      rearrangement. Thus, Ly49D that is expressed on immature B cells recognizes MHC
      class I on the peripheral tissues, inducing the secretion of low levels of IFN
      gamma and thereby down-regulating immature B cell homing to the lymph nodes or to
      sites of inflammation.

PMID- 14568938
TI  - Estimating hypermutation rates from clonal tree data.
AB  - To understand the mechanisms underlying the varying patterns of mutations that
      occur during immune and autoimmune responses, estimates of the somatic
      hypermutation rate are critical. However, despite its significance, precise
      estimates of the mutation rate do not currently exist. Microdissection studies of
      mutating B cell clones provide an opportunity to measure this rate more
      accurately than previously possible. Each microdissection provides a number of
      clonally related sequences that, through the analysis of shared mutations, can be
      genealogically related to each other. The shape of these clonal trees is
      influenced by many processes, including the hypermutation rate. We have developed
      two different methods to estimate the mutation rate based on these data. These
      methods are applied to two sets of experimental data, one from an autoimmune
      response and one from the antihapten response to (4-hydroxy-3-nitrophenyl)acetyl
      (NP). Comparable mutation rates are estimated for both responses, 0.7-0.9 x 10(
      3) and 0.9-1.1 x 10(-3) bp(-1) division(-1) for the autoimmune and NP responses,
      respectively. In addition to comparing the results of the two procedures, we
      investigate the effect on our estimate of assumptions, such as the fraction of
      lethal mutations.

PMID- 14568940
TI  - A novel interaction between protein kinase D and TNF receptor-associated factor
      molecules regulates B cell receptor-CD40 synergy.
AB  - Signaling by Ag to the B cell Ag receptor (BCR) is enhanced by several
      cooperating signals, including several provided by B-T cell interactions. One of
      these, CD40, provides critical signals for B cell differentiation, isotype
      switching, and B cell memory. The molecular mechanisms by which BCR and CD40
      signals synergize are not well understood. Although the BCR and CD40 share
      certain signaling pathways, we hypothesized that unique signals provided by each
      could provide mutual enhancement of their signaling pathways. The BCR, but not
      CD40, activates protein kinase D (PKD), while CD40, but not the BCR, employs the
      TNFR-associated factor (TRAF) adapter proteins in signaling. In this study, we
      show that genetic or pharmacologic inhibition of BCR-mediated PKD activation in B
      lymphocytes abrogated the synergy between the CD40 and the BCR, as measured by
      activation of Ig and cytokine secretion. Interestingly, the role of PKD was
      dependent upon the association of CD40 with TRAF2, and was inhibited by the
      binding of TRAF3, revealing a novel functional link between these two classes of
      signaling molecules.

PMID- 14568939
TI  - Genomic organization and expression analysis of B7-H4, an immune inhibitory
      molecule of the B7 family.
AB  - B7-H4 is a recently identified B7 family member that negatively regulates T cell
      immunity by the inhibition of T cell proliferation, cytokine production, and cell
      cycle progression. In this study, we report that the genomic DNA of human B7-H4
      is mapped on chromosome 1 comprised of six exons and five introns spanning 66 kb,
      of which exon 6 is used for alternative splicing to generate two different
      transcripts. Similar B7-H4 structure is also found in mouse genomic DNA in
      chromosome 3. A human B7-H4 pseudogene is identified in chromosome 20p11.1 with a
      single exon and two stop codons in the coding region. Immunohistochemistry
      analysis using B7-H4-specific mAb demonstrates that B7-H4 is not expressed on the
      majority of normal human tissues. In contrast, up to 85% (22 of 26) of ovarian
      cancer and 31% (5 of 16) of lung cancer tissues constitutively express B7-H4. Our
      results indicate a tight regulation of B7-H4 expression in the translational
      level in normal peripheral tissues and a potential role of B7-H4 in the evasion
      of tumor immunity.

PMID- 14568941
TI  - Selection of Ig mu heavy chains by complementarity-determining region 3 length
      and amino acid composition.
AB  - Although it is generally accepted that Ig heavy chains (HC) are selected at the
      pre-B cell receptor (pre-BCR) checkpoint, the characteristics of a functional HC
      and the role of pre-BCR assembly in their selection have remained elusive. We
      determined the characteristics of HCs that successfully passed the pre-BCR
      checkpoint by examining transcripts harboring V(H)81X and J(H)4 gene segments
      from J(H)(+/-) and lambda5(-/-)mice. V(H)81X-J(H)4-HC transcripts isolated from
      cells before or in the absence of pre-BCR assembly had no distinguishing
      complementarity-determining region 3 traits. In contrast, transcripts isolated
      subsequent to passage through the pre-BCR checkpoint had distinctive
      complementarity-determining regions 3 of nine amino acids in length (49%) and a
      histidine at position 1 (73%). Hence, our data define specific structural
      requirements for a functional HC, which is instrumental in shaping the diverse B
      cell repertoire.

PMID- 14568942
TI  - Silent cleanup of very early apoptotic cells by macrophages.
AB  - Apoptotic cells are phagocytosed as soon as they appear in vivo. In this study,
      we first determined precisely at what stage apoptotic cells are phagocytosed by
      macrophages, and then examined the subsequent cytokine production. Phagocytosis
      was confirmed by flow cytometry and confocal laser microscopy, whereas the
      subsequent response was examined by ELISA and RT-PCR for quantitative and
      semiquantitative measurement of the protein and mRNA levels of cytokines,
      respectively. Even the cell populations containing very early apoptotic cells,
      such as IL-2-dependent CTLL-2 cells cultured in the absence of IL-2 for 4 h and a
      murine leukemic cell line, P388 cells, treated with etoposide for 5 h, were
      phagocytosed by macrophages. Although the cell populations containing the very
      early apoptotic cells used in this study were FITC-Annexin V-negative and did not
      show a decrease in cell size as compared with untreated cells, they showed a very
      small increase in phosphatidylserine on the cell surface, as detected with Cy3
      Annexin V, and a decrease in mitochondrial membrane potential, indicating that
      the cell populations had already started the apoptotic process. Phagocytosis of
      such populations containing very early apoptotic cells was inhibited by phospho-L
      serine much more significantly than Arg-Gly-Asp-Ser. In addition, macrophages
      hardly produced either proinflammatory or anti-inflammatory cytokines after
      phagocytosis, thus being an almost null response. These results are contrary to
      the generally accepted concept that the phagocytosis of apoptotic cells leads to
      the production of anti-inflammatory cytokines, suggesting instead that cells
      starting to undergo apoptosis are quickly phagocytosed by macrophages without any
      inflammation in vivo.

PMID- 14568943
TI  - Infant and adult human B cell responses to rotavirus share common immunodominant
      variable gene repertoires.
AB  - Ab repertoires exhibit marked restrictions during fetal life characterized by
      biases of variable gene usage and lack of junctional diversity. We tested the
      hypothesis that Ab repertoire restriction contributes to the observed poor
      quality of specific Ab responses made by infants to viral infections. We analyzed
      the molecular determinants of B cell responses in humans to two Ags of rotavirus
      (RV), a common and clinically important infection of human infants. We sequenced
      Ab H and L chain V region genes (V(H) and V(L)) of clones expanded from single B
      cells responding to RV virus protein 6 or virus protein 7. We found that adults
      exhibited a distinct bias in use of gene segments in the V(H)1 and V(H)4
      families, for example, V(H)1-46, V(H)4-31, and V(H)4-61. This gene segment bias
      differed markedly from the V(H)3 dominant bias seen in randomly selected adult B
      cells. Recombinant Abs incorporating any of those three immunodominant V(H)
      segments bound to RV-infected cells and also to purified RV particles. The RV
      specific B cell repertoires of infants aged 2-11 mo and those of adults were
      highly related when compared by V(H), D, J(H), V(L), and J(L) segment selection,
      extent of junctional diversity, and mean H chain complementarity determining
      region 3 length. These data suggest that residual fetal bias of the B cell
      repertoire is not a limiting determinant of the quality of Ab responses to
      viruses of infants beyond the neonatal period.

PMID- 14568944
TI  - CD4+ T cells mediate IFN-gamma-independent control of Mycobacterium tuberculosis
      infection both in vitro and in vivo.
AB  - Although IFN-gamma is necessary for survival of Mycobacterium tuberculosis
      infection in people and animal models, it may not be sufficient to clear the
      infection, and IFN-gamma is not a reliable correlate of protection. To determine
      whether IFN-gamma-independent mechanisms of immunity exist, we developed a murine
      ex vivo culture system that directly evaluates the ability of splenic or lung
      lymphocytes to control the growth of M. tuberculosis within infected macrophages,
      and that models in vivo immunity to tuberculosis. Surprisingly, CD4(+) T cells
      controlled >90% of intracellular M. tuberculosis growth in the complete absence
      of IFN-gamma stimulation of macrophages, via a NO-dependent mechanism.
      Furthermore, bacillus Calmette-Guerin-vaccinated IFN-gamma-deficient mice
      exhibited significant protection against M. tuberculosis challenge that was lost
      upon depletion of CD4(+) T cells. These findings demonstrate that CD4(+) T cells
      possess IFN-gamma-independent mechanisms that can limit the growth of an
      intracellular pathogen and are dominant in secondary responses to M.
      tuberculosis.

PMID- 14568945
TI  - TNF-alpha-dependent ICAM-1- and VCAM-1-mediated inflammatory responses are
      delayed in neonatal mice infected with Pneumocystis carinii.
AB  - Neonatal mice have a delayed CD4-mediated inflammatory response to Pneumocystis
      carinii (PC) infection in the lungs that corresponds to a delayed TNF-alpha
      response and a delayed clearance of the organisms compared with adult mice. Since
      TNF-alpha is known to drive the up-regulation of adhesion molecules, we examined
      the expression and function of adhesion molecules in the lungs of neonatal mice.
      The expression of both ICAM-1 and VCAM-1 was significantly lower in the lungs of
      PC-infected neonatal mice compared with adults. Additionally, migration of
      neonatal T cells across endothelial cells expressing VCAM-1 and monocyte
      chemotactic protein-1 was aberrant compared with that in adult T cells, although
      alpha(4)beta(1) integrin-mediated adhesion of neonatal lymphocytes was comparable
      to that of adult lymphocytes. Treatment of neonatal mice with exogenous TNF-alpha
      resulted in increased expression of ICAM-1 and VCAM-1 as well as increased
      expression of chemokines, resulting in infiltration of CD4(+) cells into the
      lungs. Treatment with exogenous TNF-alpha resulted in a trend (although not
      statistically significant) toward a reduction of PC organisms from the lungs.
      These data indicate that neonatal lung endothelial cells do not up-regulate ICAM
      1 and VCAM-1 in response to PC infection, probably due to depressed TNF-alpha
      production. Additionally, neonatal T cells are defective in the ability to
      migrate across endothelial cells.

PMID- 14568946
TI  - IL-4 suppresses the expression and the replication of hepatitis B virus in the
      hepatocellular carcinoma cell line Hep3B.
AB  - IL-4 has been known as a Th2 cytokine and can act on B cells, T cells, and
      monocytes. In this study we demonstrate that IL-4Rs are expressed on human
      hepatocellular carcinoma (HCC) cells. We found that IL-4 suppresses hepatitis B
      surface Ag (HBsAg) mRNA and HBsAg production in the Hep3B cell line, which
      contains an integrated hepatitis B virus (HBV) genome and constitutively secretes
      HBsAg. When Hep3B cells are further transfected with the plasmid pHBV3.6 that
      contains >1 U of HBV genome, IL-4 could suppress the production of all HBV RNA
      and secreted HBsAg and hepatitis B virus e Ag. Furthermore, an endogenous DNA
      polymerase activity assay shows a decrease in HBV DNA after IL-4 treatment. Using
      luciferase reporter assays we have demonstrated that IL-4 could suppress the
      activity of the surface promoter II and the core promotor (CP). To delineate how
      IL-4 suppressed the transcription of HBV genes, we have examined the effect of IL
      4 on the expression of transcription factors that are known to bind to the core
      upstream regulatory sequence, which colocalizes with enhancer II of the HBV
      genome. Our results demonstrate that IL-4 suppresses the expression of
      C/EBPalpha. Furthermore, overexpression of C/EBPalpha blocked 43 and 30% of the
      IL-4-mediated suppression of CP activity and IL-4-induced suppression of
      pregenomic RNA, respectively. Finally, we have demonstrated that mutations
      affecting the C/EBPalpha-binding sites on core upstream regulatory
      sequence/enhancer II completely abolish the IL-4-mediated suppression of CP
      activity. Thus, down-regulation of C/EBPalpha may be involved in the anti-HBV
      effect of IL-4 in Hep3B cells.

PMID- 14568947
TI  - M cell DNA vaccination for CTL immunity to HIV.
AB  - To facilitate invasion, reovirus has evolved to attach to M cells, a specialized
      epithelium residing within the follicle-associated epithelium that covers mucosal
      inductive tissues. Thus, we questioned adapting reovirus protein sigma1 to ferry
      DNA vaccines to the mucosa to immunize against HIV. Three expression plasmids
      encoding HIV(Ba-L) gp160, cytoplasmic gp140, and secreted gp140 were tested in
      mice as protein sigma1-poly-L-lysine-DNA complexes (formulated vaccine) via the
      intranasal route. Evaluation of cell-mediated immunity showed that the formulated
      gp160 DNA vaccine was more effective for stimulating envelope (Env)-specific CTL
      responses in lungs, lower respiratory lymph nodes (LN), cervical LN, submaxillary
      gland LN, and spleens. Three doses of vaccine were required for CTL responses,
      and intranasal naked DNA immunizations were ineffective. The greatest CTL
      activity was observed between weeks 8 and 10 for gp160-vaccinated mice, and
      activity remained detectable by week 16. These Env-specific CTL responses were
      perforin dependent in peripheral tissues, but mostly Fas dependent in the lungs.
      These Env-specific CTLs also produced IFN-gamma. Mice vaccinated with the
      formulated gp160 DNA vaccine showed potent antiviral immunity against vaccinia
      virus-env replication in ovaries. Thus, compared with live vectors, protein
      sigma1-mediated DNA delivery represents an alternative mucosal formulation for
      inducing cellular immunity against HIV-1.

PMID- 14568948
TI  - Th1 cell-mediated resistance to cutaneous infection with Leishmania major is
      independent of P- and E-selectins.
AB  - Studies in several models of inflammation have underscored the importance of P-
      and E-selectins in the migration of T cells to inflamed tissues. However, the
      role of the endothelial selectins in infection-induced cutaneous inflammation and
      host-protective immunity has not been investigated. In this study, we demonstrate
      that CD4(+) T cells recruited to the cutaneous compartment during infection with
      Leishmania major express P- and E-selectin ligands. Furthermore, expression of P-
      and E-selectin ligands correlates with activated Leishmania-specific Th1 cells
      and is dependent upon IL-12. To investigate the functional role of the
      endothelial selectins during leishmaniasis, we infected mice either singly or
      doubly deficient in the expression of P- and E- selectins. Mice lacking both P-
      and E-selectins developed significantly less inflammation at the site of a
      primary and secondary infection, and exhibited an impaired delayed-type
      hypersensitivity response. Surprisingly, the absence of the endothelial selectins
      had no effect on the control of parasite replication or immunity to reinfection.
      Thus, these data demonstrate that although the endothelial selectins contribute
      to the inflammatory response, they are not required for protective immunity to L.
      major. Moreover, these data suggest that by blocking P- and E-selectins, the
      immune pathology associated with cutaneous leishmaniasis might be ameliorated
      without compromising immunity to infection.

PMID- 14568949
TI  - Deficient CD4+ T cell priming and regression of CD8+ T cell functionality in
      virus-infected mice lacking a normal B cell compartment.
AB  - In this study, we investigate the state of T cell-mediated immunity in B cell
      deficient (B(-/-)) mice infected with two strains of lymphocytic choriomeningitis
      virus known to differ markedly in their capacity to persist. In B(-/-) C57BL mice
      infected with the more persisting virus, virus-specific CD8(+) T cells are
      initially generated that are qualitatively similar to those in wild-type mice.
      However, although cell numbers are well sustained over time, the capacity to
      produce cytokines is rapidly impaired. In similarly infected B(-/-) BALB/c mice,
      virus-specific CD8(+) T cells are completely deleted, indicating that host
      genotype influences the severity of the T cell defect. In B(-/-) C57BL mice
      infected with the less persisting virus, CD8(+) T cell dysfunction was not as
      pronounced, although it was clearly present. Most importantly, the appearance of
      dysfunctional CD8(+) T cells clearly precedes recrudescence of detectable virus,
      indicating that the T cell defect is not simply a secondary event due to virus
      buildup resulting from the failure of B(-/-) mice to produce neutralizing Abs. In
      contrast with CD8(+) T cells, which initially respond almost as in wild-type
      mice, the priming of virus-specific CD4(+) T cells was markedly impaired in B(-/
      ) mice infected with either virus strain. Thus, our results indicate that B cells
      play an important role in antiviral immunity not only as Ab producers, but also
      in promoting an optimal and sustained T cell response. The T cell defects are
      likely to contribute to the chronic course of viral infection in B(-/-) mice.

PMID- 14568950
TI  - An inclusion membrane protein from Chlamydia trachomatis enters the MHC class I
      pathway and stimulates a CD8+ T cell response.
AB  - During its developmental cycle, the intracellular bacterial pathogen Chlamydia
      trachomatis remains confined within a protective vacuole known as an inclusion.
      Nevertheless, CD8(+) T cells that recognize Chlamydia Ags in the context of MHC
      class I molecules are primed during infection. MHC class I-restricted
      presentation of these Ags suggests that these proteins or domains from them have
      access to the host cell cytoplasm. Chlamydia products with access to the host
      cell cytoplasm define a subset of molecules uniquely positioned to interface with
      the intracellular environment during the pathogen's developmental cycle. In
      addition to their use as candidate Ags for stimulating CD8(+) T cells, these
      proteins represent novel candidates for therapeutic intervention of infection. In
      this study, we use C. trachomatis-specific murine T cells and an expression
      cloning strategy to show that CT442 from Chlamydia is targeted by CD8(+) T cells.
      CT442, also known as CrpA, is a 15-kDa protein of undefined function that has
      previously been shown to be associated with the Chlamydia inclusion membrane. We
      show that: 1) CD8(+) T cells specific for an H-2D(b)-restricted epitope from CrpA
      are elicited at a significant level (approximately 4% of splenic CD8(+) T cells)
      in mice in response to infection; 2) the response to this epitope correlates with
      clearance of the organism from infected mice; and 3) immunization with
      recombinant vaccinia virus expressing CrpA elicits partial protective immunity to
      subsequent i.v. challenge with C. trachomatis.

PMID- 14568951
TI  - Innate inhibition of adaptive immunity: Mycobacterium tuberculosis-induced IL-6
      inhibits macrophage responses to IFN-gamma.
AB  - In humans and in mice, control of the intracellular pathogen, Mycobacterium
      tuberculosis (Mtb), requires IFN-gamma. Although the adaptive immune response
      results in production of substantial amounts of IFN-gamma in response to Mtb, the
      immune response is unable to eradicate the infection in most cases. We have
      previously reported evidence that Mtb inhibits macrophage responses to IFN-gamma,
      suggesting that this may limit the ability of IFN-gamma to stimulate macrophages
      to kill Mtb. We have also observed that uninfected macrophages, adjacent to
      infected macrophages in culture, exhibit decreased responses to IFN-gamma. Here
      we report that IL-6 secreted by Mtb-infected macrophages inhibits the responses
      of uninfected macrophages to IFN-gamma. IL-6 selectively inhibits a subset of IFN
      gamma-responsive genes at the level of transcriptional activation without
      inhibiting activation or function of STAT1. Inhibition of macrophage responses to
      IFN-gamma by IL-6 requires new protein synthesis, but this effect is not
      attributable to suppressor of cytokine signaling 1 or 3. These results reveal a
      novel function for IL-6 and indicate that IL-6 secreted by Mtb-infected
      macrophages may contribute to the inability of the cellular immune response to
      eradicate infection.

PMID- 14568952
TI  - Mice lacking myeloid differentiation factor 88 display profound defects in host
      resistance and immune responses to Mycobacterium avium infection not exhibited by
      Toll-like receptor 2 (TLR2)- and TLR4-deficient animals.
AB  - To assess the role of Toll-like receptor (TLR) signaling in host resistance to
      Mycobacterium avium infection, mice deficient in the TLR adaptor molecule myeloid
      differentiation factor 88 (MyD88), as well as TLR2(-/-) and TLR4(-/-) animals,
      were infected with a virulent strain of M. avium, and bacterial burdens and
      immune responses were compared with those in wild-type (WT) animals. MyD88(-/-)
      mice failed to control acute and chronic M. avium growth and succumbed 9-14 wk
      postinfection. Infected TLR2(-/-) mice also showed increased susceptibility, but
      displayed longer survival and lower bacterial burdens than MyD88(-/-) animals,
      while TLR4(-/-) mice were indistinguishable from their WT counterparts.
      Histopathological examination of MyD88(-/-) mice revealed massive destruction of
      lung tissue not present in WT, TLR2(-/-), or TLR4(-/-) mice. In addition, MyD88(
      /-) and TLR2(-/-), but not TLR4(-/-), mice displayed marked reductions in hepatic
      neutrophil infiltration during the first 2 h of infection. Although both MyD88(-/
      ) and TLR2(-/-) macrophages showed profound defects in IL-6, TNF, and IL-12p40
      responses to M. avium stimulation in vitro, in vivo TNF and IL-12p40 mRNA
      induction was impaired only in infected MyD88(-/-) mice. Similarly, MyD88(-/-)
      mice displayed a profound defect in IFN-gamma response that was not evident in
      TLR2(-/-) or TLR4(-/-) mice or in animals deficient in IL-18. These findings
      indicate that resistance to mycobacterial infection is regulated by multiple
      MyD88-dependent signals in addition to those previously attributed to TLR2 or
      TLR4, and that these undefined elements play a major role in determining
      bacterial induced proinflammatory as well as IFN-gamma responses.

PMID- 14568953
TI  - IL-10 mediates suppression of the CD8 T cell IFN-gamma response to a novel viral
      epitope in a primed host.
AB  - Priming to Ag can inhibit subsequent induction of an immune response to a new
      epitope incorporated into that Ag, a phenomenon referred to as original antigenic
      sin. In this study, we show that prior immunity to a virus capsid can inhibit
      subsequent induction of the IFN-gamma effector T cell response to a novel CD8
      restricted antigenic epitope associated with the virus capsid. Inhibition does
      not involve Ab to the virus capsid, as it is observed in animals lacking B cells.
      CD8-restricted virus-specific T cell responses are not required, as priming to
      virus without CTL induction is associated with inhibition. However, IL-10(-/-)
      mice, in contrast to IL-10(+/+) mice, generate CD8 T cell and Ab responses to
      novel epitopes incorporated into a virus capsid, even when priming to the capsid
      has resulted in high titer Ab to the capsid. Furthermore, capsid-primed mice,
      unable to mount a response to a novel epitope in the capsid protein, are
      nevertheless able to respond to the same novel epitope delivered independently of
      the capsid. Thus, inhibition of responsiveness to a novel epitope in a virus
      primed animal is a consequence of secretion of IL-10 in response to presented Ag,
      which inhibits local generation of new CD8 IFN-gamma-secreting effector T cells.
      Induction of virus- or tumor Ag-specific CD8 effector T cells in the partially Ag
      primed host may thus be facilitated by local neutralization of IL-10.

PMID- 14568954
TI  - Inhibition of neutrophil leukotriene B4 production by a novel synthetic N-3
      polyunsaturated fatty acid analogue, beta-oxa 21:3n-3.
AB  - We recently reported the synthesis and anti-inflammatory properties of a novel
      long chain polyunsaturated fatty acid (PUFA) with an oxygen atom in the beta
      position, beta-oxa-21:3 n-3 (Z,Z,Z)-(octadeca-9,12,15-trienyloxy) acetic acid).
      Our data, from studies aimed at elucidating the mechanism of its action, show
      that pretreatment of human neutrophils with the beta-oxa-PUFA substantially
      depresses the production of leukotriene B(4) (LTB(4)) in response to calcium
      ionophore, A23187, comparable to standard leukotriene inhibitors such as zileuton
      and nordihydroguaiaretic acid. Interestingly, the n-6 equivalent, beta-oxa 21:3 n
      6, is also a strong inhibitor of LTB(4) production. In contrast, naturally
      occurring PUFA only slightly reduce, for eicosapentaenoic (20:5n-3) and
      docosahexaenoic (22:6n-3) acids, or increase, for arachidonic acid (20:4n-6), the
      formation of LTB(4). The parent beta-oxa-21:3n-3 molecule, rather than its
      derivatives (methyl ester, saturated, monohydroperoxy, or monohydroxy forms), is
      exclusively responsible for attenuation of LTB(4) formation. beta-Oxa-21:3n-3
      inhibits the conversion of [(3)H]20:4n-6 to [(3)H]5-hydroxyeicosatetraenoic acid
      and [(3)H]LTB(4) by neutrophils in the presence of calcium ionophore and also
      suppresses the activity of purified 5-lipoxygenase, but not cyclooxygenase 1 and
      2. Beta-oxa-21:3n-3 is taken up by neutrophils and incorporated into
      phospholipids and neutral lipids. In the presence of calcium ionophore, the
      leukocytes convert a marginal amount of beta-oxa-21:3n-3 to a 16-monohydroxy-beta
      oxa-21:3n-3 derivative. After administration to rodents by gavage or i.p.
      injection, beta-oxa-21:3n-3 is found to be incorporated into the lipids of
      various tissues. Thus, beta-oxa-21:3n-3 has the potential to be used in the
      treatment of inflammatory diseases, which are mediated by products of the
      lipoxygenase pathway.

PMID- 14568955
TI  - CpG-containing oligodeoxynucleotide 1826 converts the weak uveitogenic rat
      interphotoreceptor retinoid-binding protein peptide 1181-1191 into a strong
      uveitogen.
AB  - Aberrant activation of autoreactive T cells is one of the major causes of
      autoimmune disease. Autoantigens are sequestered and in many cases weak
      immunogens. For example, in experimental autoimmune uveitis, immunization of
      naive rats with autologous interphotoreceptor retinoid-binding protein (IRBP)
      fails to induce intraocular inflammation or a strong T cell response, whereas
      bovine IRBP is a strong inducer of experimental autoimmune uveitis. Such
      observations challenge the view that the autoantigen alone is responsible for the
      development of autoimmunity. Here, we demonstrate that autologous rat IRBP is
      converted to a strong immunogen in the presence of a small dose of CpG-containing
      oligodeoxynucleotides. Our results indicate that specific CpG-containing
      oligodeoxynucleotides may play an important role in the activation and expansion
      of autoreactive T cells in vivo, leading to autoimmune disease.

PMID- 14568956
TI  - Complement regulatory protein C1 inhibitor binds to selectins and interferes with
      endothelial-leukocyte adhesion.
AB  - C1 inhibitor (C1INH), a member of the serine proteinase inhibitor (serpin)
      family, is an inhibitor of proteases in the complement system, the contact system
      of kinin generation, and the intrinsic coagulation pathway. It is the most
      heavily glycosylated plasma protein, containing 13 definitively identified
      glycosylation sites as well as an additional 7 potential glycosylation sites.
      C1INH consists of two distinct domains: a serpin domain and an amino-terminal
      domain. The serpin domain retains all the protease-inhibitory function, while the
      amino-terminal domain bears most of the glycosylation sites. The present studies
      test the hypothesis that plasma C1INH bears sialyl Lewis(x)-related moieties and
      therefore binds to selectin adhesion molecules. We demonstrated that plasma C1INH
      does express sialyl Lewis(x)-related moieties on its N-glycan as detected using
      mAb HECA-452 and CSLEX1. The data also show that plasma C1INH can bind to P- and
      E-selectins by FACS and immunoprecipitation experiments. In a tissue culture
      model of endothelial-leukocyte adhesion, C1INH showed inhibition in a dose
      dependent manner. Significant inhibition (>50%) was achieved at a concentration
      of 250 micro g/ml or higher. This discovery may suggest that C1INH plays a role
      in the endothelial-leukocyte interaction during inflammation. It may also provide
      another example of the multifaceted anti-inflammatory effects of C1INH in various
      animal models and human diseases.

PMID- 14568957
TI  - Novel and detrimental effects of lipopolysaccharide on in vitro generation of
      immature dendritic cells: involvement of mitogen-activated protein kinase p38.
AB  - Dendritic cells (DCs) are recognized as major players in the regulation of immune
      responses to a variety of Ags, including bacterial agents. LPS, a Gram-negative
      bacterial cell wall component, has been shown to fully activate DCs both in vitro
      and in vivo. LPS-induced DC maturation involves activation of p38, extracellular
      signal-regulated kinase (ERK)/mitogen-activated protein kinases, and NF-kappaB.
      Blocking p38 inhibits LPS-induced maturation of DCs. In this study we
      investigated the role of LPS in the in vitro generation of immature DCs. We
      report here that in contrast to the observed beneficial effects on DCs, the
      presence of LPS in monocyte culture retarded the generation of immature DCs. LPS
      not only impaired the morphology and reduced the yields of the cultured cells,
      but also inhibited the up-regulation of surface expression of CD1a, costimulatory
      and adhesion molecules. Furthermore, LPS up-regulated the secretion of IL-1beta,
      IL-6, IL-8, IL-10, and TNF-alpha; reduced Ag presentation capacity; and inhibited
      phosphorylation of ERK, but activated p38, leading to a reduced NF-kappaB
      activity in treated cells. Neutralizing Ab against IL-10, but not other
      cytokines, partially blocked the effects of LPS. Inhibiting p38 (by inhibitor
      SB203580) restored the morphology, phenotype, and Ag presentation capacity of LPS
      treated cells. SB203580 also inhibited LPS-induced production of IL-1beta, IL-10,
      and TNF-alpha; enhanced IL-12 production; and recovered the activity of ERK and
      NF-kappaB. Thus, our study reveals that LPS has dual effects on DCs that are
      biologically important: activating existing DCs to initiate an immune response,
      and inhibiting the generation of new DCs to limit such a response.

PMID- 14568958
TI  - In vivo impairment of neutrophil recruitment during lentivirus infection.
AB  - Evidence indicates that the lentivirus, HIV, infection affects neutrophil
      response to bacteria and bacterial products in vitro. We used a novel model of
      rapid onset immunosuppression following infection with a similar lentivirus,
      feline immunodeficiency virus (FIV), in cats to examine neutrophil function
      within the microvasculature in vivo and to determine the steps that are impaired
      in the neutrophil recruitment cascade. In uninfected cats and cats infected
      neonatally with FIV, the mesentery was exteriorized, but remained autoperfused
      during intravital microscopy for 4 h. When the tissue was superfused with 10
      micro g/ml of LPS for 4 h, intravital microscopy displayed a profound increase in
      neutrophil rolling at both 8 and 12 wk of age in uninfected cats. At 12 wk of
      age, FIV-infected animals showed a profound decrease in the number of rolling
      neutrophils. In vitro studies revealed that neutrophils from infected and
      uninfected animals rolled equally well on surrogate selectin substrata. In
      addition, in vivo neutrophil adhesion and emigration out of the vasculature were
      severely reduced, and in vitro neutrophil chemotaxis from FIV-infected animals
      was significantly impaired in response to fMLP or IL-8. However, FIV infection of
      neutrophils could not be detected. In summary, in vivo lentivirus infection with
      immunosuppression leads to a severe impairment in neutrophil rolling, adhesion,
      and emigration in response to bacterial stimulants potentially involving both
      endothelial and neutrophil dysfunction. These in vivo studies also indicate that
      neutrophil dysfunction should be taken into account when treating infections and
      tissue injury.

PMID- 14568959
TI  - Nitric oxide regulation of human peripheral blood mononuclear cells: critical
      time dependence and selectivity for cytokine versus chemokine expression.
AB  - NO is antiproliferative for T cells and other immune cells, but there is debate
      over whether it influences cytokine expression and if so whether it shows
      cytokine selectivity. Furthermore, the NO effect may depend on exposure time. To
      address these issues, we precultured human PBMC with the NO donors S
      nitrosoglutathione (a natural storage form of NO) or S-nitroso-N-acetyl-D
      penicillamine for up to 48 h before cell activation and then monitored
      proliferation and cytokine and chemokine expression. S-nitrosoglutathione or S
      nitroso-N-acetyl-D-penicillamine, but not their non-NO-releasing analogues,
      inhibited proliferation induced by PHA or IL-2, the effect declining
      progressively from 48 to 0 h pre-exposure to the mitogen. This was accompanied by
      reduced PHA-induced IL-2 release and reduced IL-2, IFN-gamma, and IL-13 mRNA
      expression. In contrast, NO did not influence PHA-induced expression of mRNA for
      the chemokines lymphotactin, RANTES, IFN-gamma-inducible protein, macrophage
      inhibitory protein-1alpha, macrophage-inhibitory protein-1beta, macrophage
      chemoattractant protein-1, and IL-8 or release of RANTES or IL-8. The NO effects
      were not toxic and were not accompanied by changes in PHA-induced CD25
      expression. We conclude that exposure time to NO is critical to altered PBMC
      responsiveness and that NO inhibits expression of both Th1 and Th2 cytokines but
      not chemokines.

PMID- 14568960
TI  - The phenotype of inflammatory macrophages is stimulus dependent: implications for
      the nature of the inflammatory response.
AB  - Many diseases are characterized by inflammatory reactions involving both the
      innate and adaptive arms of the immune system. Thioglycolate medium (TM)
      injection into the peritoneal cavity has long been used as a stimulus for
      eliciting inflammatory macrophages for study and for determining the importance
      of a particular mediator in inflammation. However, the response to this irritant
      may not be relevant to many inflammatory diseases. Therefore, we have developed
      an Ag-specific peritonitis model using methylated BSA (mBSA) as the stimulus.
      Priming mice intradermally with mBSA in adjuvant and boosting 14 days later,
      followed by an i.p. challenge with mBSA after an additional 7 days, led to an
      inflammatory reaction equivalent in magnitude to that induced with TM as judged
      by the number of exudate cells. The inflammatory macrophages elicited by the mBSA
      protocol differed, being smaller and less vacuolated than TM-elicited
      macrophages. Also, macrophages from 4-day mBSA-induced exudates expressed more
      MHC class II than TM-induced exudates, were able to stimulate allogeneic T
      lymphocytes, and upon in vitro stimulation with LPS secreted greater levels of IL
      6 and IL-1beta. Macrophages from 4-day TM-induced exudates, on the other hand,
      expressed Ly6C and ER-MP58, immature myeloid markers. The inflammatory response
      elicited using the Ag mBSA may be more relevant for studying the inflammatory
      responses in many diseases, such as those of autoimmune origin and those
      involving an acquired immune response.

PMID- 14568961
TI  - DNA vaccination against specific pathogenic TCRs reduces proteinuria in active
      Heymann nephritis by inducing specific autoantibodies.
AB  - We have previously identified potential pathogenic T cells within glomeruli that
      use TCR encoding Vbeta5, Vbeta7, and Vbeta13 in combination with Jbeta2.6 in
      Heymann nephritis (HN), a rat autoimmune disease model of human membranous
      nephritis. Vaccination of Lewis rats with naked DNA encoding these pathogenic
      TCRs significantly protected against HN. Proteinuria was reduced at 6, 8, 10, and
      12 wk after immunization with Fx1A (p < 0.001). Glomerular infiltrates of
      macrophages and CD8(+) T cells (p < 0.005) and glomerular IFN-gamma mRNA
      expression (p < 0.01) were also significantly decreased. DNA vaccination (DV)
      causes a loss of clonality of T cells in the HN glomeruli. T lymphocytes with
      surface binding of Abs were found in DNA vaccinated rats. These CD3(+)/IgG(+) T
      cells expressed Vbeta5 and Vbeta13 that the DV encoded. Furthermore, FACS shows
      that these CD3(+)/IgG(+) cells were CD8(+) T cells. Analysis of cytokine mRNA
      expression showed that IL-10 and IFN-gamma mRNA were not detected in these
      CD3(+)/IgG(+) T cells. These results suggest that TCR DNA vaccination produces
      specific autoantibodies bound to the TCRs encoded by the vaccine, resulting in
      blocking activation of the specific T cells. In this study, we have shown that
      treatment with TCR-based DV, targeting previously identified pathogenic Vbeta
      families, protects against HN, and that the mechanism may involve the production
      of specific anti-TCR Abs.

PMID- 14568962
TI  - IL-1 induces vesicular secretion of IL-6 without degranulation from human mast
      cells.
AB  - Fc epsilon RI cross-linkage in mast cells results in release of granule
      associated mediators, such as histamine and proteases, as well as the production
      of numerous cytokines, including IL-6. Mast cells have been increasingly
      implicated in inflammatory processes where explosive degranulation is not
      commonly observed. Here, we show that IL-1 stimulates secretion of IL-6 without
      release of the granule-associated protease tryptase in normal human umbilical
      cord blood-derived mast cells (hCBMCs). IL-6 secretion stimulated by IL-1 in
      hCBMCs is potentiated by priming with IL-4 and reflects the higher levels of IL-6
      secreted from human leukemic mast cell line (HMC-1). Stimulating HMC-1 cells by
      both IL-1 and TNF-alpha results in synergistic secretion of IL-6. IL-6 is de novo
      synthesized, as its secretion is blocked by inhibitors of transcription or
      protein synthesis. IL-1 does not increase intracellular calcium ion levels in
      either hCBMCs or HMC-1 cells, and IL-6 stimulation proceeds in the absence of
      extracellular calcium ions. Ultrastructural Immunogold localization shows that IL
      6 is excluded from the secretory granules and is compartmentalized in 40- to 80
      nm vesicular structures. Selective secretion of IL-6 from mast cells appears
      distinct from degranulation and may contribute to the development of
      inflammation, where the importance of IL-6 has been recognized.

PMID- 14568963
TI  - Short-time infusion of fish oil-based lipid emulsions, approved for parenteral
      nutrition, reduces monocyte proinflammatory cytokine generation and adhesive
      interaction with endothelium in humans.
AB  - Potential impact of omega-3 fatty acids, as contained in fish oil, on
      immunological function has been suggested because observations of reduced
      inflammatory diseases in Greenland Inuit were published. A fish oil-based lipid
      emulsion has recently been approved for parenteral nutrition in many countries.
      We investigated the influence of a short infusion course of fish oil-based (omega
      3) vs conventional (omega-6) lipid emulsion on monocyte function. In a randomized
      design, twelve healthy volunteers received omega-3 or omega-6 lipid infusion for
      48 h, with cross-over repetition of the infusion course after 3 mo. Fatty acid
      profiles, monocyte cytokine release and adhesive monocyte-endothelium interaction
      were investigated. Resultant omega-6 lipid emulsion increased plasma-free fatty
      acids including arachidonic acid, whereas the omega-3/omega-6 fatty acid ratio in
      monocyte membranes remained largely unchanged. It also caused a tendency toward
      enhanced monocyte proinflammatory cytokine release and adhesive monocyte
      endothelium interaction. In contrast, omega-3 lipid emulsion significantly
      increased the omega-3/omega-6 fatty acid ratio in the plasma-free fatty acid
      fraction and in monocyte membrane lipid pool, markedly suppressing monocyte
      generation of TNF-alpha, IL-1, IL-6, and IL-8 in response to endotoxin. In
      addition, it also significantly inhibited both monocyte-endothelium adhesion and
      transendothelial monocyte migration, although monocyte surface expression of
      relevant adhesive molecules (CD11b, CD18, CD49 days, CCR2) was unchanged.
      Although isocaloric, omega-3 and omega-6 lipid emulsions exert differential
      impact on immunological processes in humans. In addition to its nutritional
      value, fish oil-based omega-3 lipid emulsion significantly suppresses monocyte
      proinflammatory cytokine generation and features of monocyte recruitment.

PMID- 14568964
TI  - Role of CXCL9/CXCR3 chemokine biology during pathogenesis of acute lung allograft
      rejection.
AB  - Acute allograft rejection is a major complication postlung transplantation and is
      the main risk factor for the development of bronchiolitis obliterans syndrome.
      Acute rejection is characterized by intragraft infiltration of activated
      mononuclear cells. The ELR-negative CXC chemokines CXCL9, CXCL10, and CXCL11) are
      potent chemoattractants for mononuclear cells and act through their shared
      receptor, CXCR3. Elevated levels of these chemokines in bronchoalveolar lavage
      fluid have been associated with human acute lung allograft rejection. This led to
      the hypothesis that the expression of these chemokines during an allogeneic
      response promotes the recruitment of mononuclear cells, leading to acute lung
      allograft rejection. We performed studies in a rat orthotopic lung
      transplantation model of acute rejection, and demonstrated increased expression
      of CXCL9 and CXCL10 paralleling the recruitment of mononuclear cells and cells
      expressing CXCR3 to the allograft. However, CXCL9 levels were 15-fold greater
      than CXCL10 during maximal rejection. Inhibition of CXCL9 decreased intragraft
      recruitment of mononuclear cells and cellular expression of CXCR3, resulting in
      lower acute lung allograft rejection scores. Furthermore, the combination of low
      dose cyclosporin A with anti-CXCL9 therapy had more profound effects on
      intragraft leukocyte infiltration and in reducing acute allograft rejection
      scores. This supports the notion that CXCL9 interaction with cells expressing
      CXCR3 has an important role in the recruitment of mononuclear cells, a pivotal
      event in the pathogenesis of acute lung allograft rejection.

PMID- 14568965
TI  - Blockade of vascular endothelial growth factor receptor I (VEGF-RI), but not VEGF
      RII, suppresses joint destruction in the K/BxN model of rheumatoid arthritis.
AB  - It was recently shown that vascular endothelial growth factor (VEGF), a growth
      factor for endothelial cells, plays a pivotal role in rheumatoid arthritis. VEGF
      binds to specific receptors, known as VEGF-RI and VEGF-RII. We assessed the
      physical and histological effects of selective blockade of VEGF and its receptors
      in transgenic K/BxN mice, a model of rheumatoid arthritis very close to the human
      disease. Mice were treated with anti-mouse VEGF Ab, anti-mouse VEGF-RI and -RII
      Abs, and an inhibitor of VEGF-RI tyrosine kinase. Disease activity was monitored
      using clinical indexes and by histological examination. We found that synovial
      cells from arthritic joints express VEGF, VEGF-RI, and VEGF-RII. Treatment with
      anti-VEGF-RI strongly attenuated the disease throughout the study period, while
      anti-VEGF only transiently delayed disease onset. Treatment with anti-VEGF-RII
      had no effect. Anti-VEGF-RI reduced the intensity of clinical manifestations and,
      based on qualitative and semiquantitative histological analyses, prevented joint
      damage. Treatment with a VEGF-RI tyrosine kinase inhibitor almost abolished the
      disease. These results show that VEGF is a key factor in pannus development,
      acting through the VEGF-RI pathway. The observation that in vivo administration
      of specific inhibitors targeting the VEGF-RI pathway suppressed arthritis and
      prevented bone destruction opens up new possibilities for the treatment of
      rheumatoid arthritis.

PMID- 14568967
TI  - Expression, localization, and functional activity of TL1A, a novel Th1-polarizing
      cytokine in inflammatory bowel disease.
AB  - TL1A is a novel TNF-like factor that acts as a costimulator of IFN-gamma
      secretion through binding to the death domain-containing receptor, DR3. The aim
      of this study was to test the hypothesis that TL1A may play an important role in
      inflammatory bowel disease (IBD) by functioning as a Th1-polarizing cytokine. The
      expression, cellular localization, and functional activity of TL1A and DR3 were
      studied in intestinal tissue specimens as well as isolated lamina propria
      mononuclear cells from IBD patients and controls. TL1A mRNA and protein
      expression was up-regulated in IBD, particularly in involved areas of Crohn's
      disease (CD; p < 0.03 vs control). TL1A production was localized to the
      intestinal lamina propria in macrophages and CD4(+) and CD8(+) lymphocytes from
      CD patients as well as in plasma cells from ulcerative colitis patients. The
      amount of TL1A protein and the number of TL1A-positive cells correlated with the
      severity of inflammation, most significantly in CD. Increased numbers of
      immunoreactive DR3-positive T lymphocytes were detected in the intestinal lamina
      propria from IBD patients. Addition of recombinant human TL1A to cultures of PHA
      stimulated lamina propria mononuclear from CD patients significantly augmented
      IFN-gamma production by 4-fold, whereas a minimal effect was observed in control
      patients. Our study provides evidence for the first time that the novel cytokine
      TL1A may play an important role in a Th1-mediated disease such as CD.

PMID- 14568966
TI  - Accumulation of peribronchial mast cells in a mouse model of ovalbumin allergen
      induced chronic airway inflammation: modulation by immunostimulatory DNA
      sequences.
AB  - Few peribronchial mast cells are noted either in the lungs of naive mice or in
      the lungs of OVA-sensitized mice challenged acutely with OVA by inhalation. In
      this study, we demonstrate that OVA-sensitized mice exposed to repetitive OVA
      inhalation for 1-6 mo have a significant accumulation of peribronchial mast
      cells. This accumulation of peribronchial mast cells is associated with increased
      expression of the Th2 cell-derived mast cell growth factors, including IL-4 and
      IL-9, but not with the non-Th2 cell-derived mast cell growth factor, stem cell
      factor. Pretreating mice with immunostimulatory sequences (ISS) of DNA containing
      a CpG motif significantly inhibited the accumulation of peribronchial mast cells
      and the expression of IL-4 and IL-9. To determine whether mast cells express Toll
      like receptor-9 (TLR-9; the receptor for ISS), TLR-9 expression by mouse bone
      marrow-derived mast cells (MBMMCs) was assessed by RT-PCR. MBMMCs strongly
      expressed TLR-9 and bound rhodamine-labeled ISS. However, incubation of MBMMCs
      with ISS in vitro neither inhibited MBMMC proliferation nor inhibited Ag/IgE
      mediated MBMMC degranulation, but they did induce IL-6. Overall these studies
      demonstrate that mice exposed to repetitive OVA challenge, but not acute OVA
      challenge, have an accumulation of peribronchial mast cells and express increased
      levels of mast cell growth factors in the lung. Although mast cells express TLR
      9, ISS does not directly inhibit mast cell proliferation in vitro, suggesting
      that ISS inhibits accumulation of peribronchial mast cells in vivo by indirect
      mechanism(s), which include inhibiting the lung expression of Th2 cell-derived
      mast cell growth factors.

PMID- 14568968
TI  - CC chemokine receptor 2 expression in donor cells serves an essential role in
      graft-versus-host-disease.
AB  - The complete repertoire of cellular and molecular determinants that influence
      graft-vs-host disease (GVHD) is not known. Using a well-established murine model
      of GVHD (B6-->bm12 mice), we sought to elucidate the role of the donor non-T cell
      compartment and molecular determinants therein in the pathogenesis of GVHD. In
      this model the acute GVHD-inducing effects of purified B6 wild-type (wt) CD4(+) T
      cells was inhibited by wt non-T cells in a dose-dependent manner. Paradoxically,
      unlike the chronic GVHD phenotype observed in bm12 mice transplanted with B6wt
      unfractionated splenocytes, bm12 recipients of B6ccr2-null unfractionated
      splenocytes developed acute GVHD and died of IFN-gamma-mediated bone marrow
      aplasia. This switch from chronic to acute GVHD was associated with increased
      target organ infiltration of activated CD4(+) T cells as well as enhanced
      expression of Th1/Th2 cytokines, chemokines, and the antiapoptotic factor bfl1.
      In vitro, ccr2(-/-) CD4(+) T cells in unfractionated splenocytes underwent
      significantly less activation-induced cell death than B6wt CD4(+) T cells,
      providing another potential mechanistic basis along with enhanced expression of
      bfl1 for the increased numbers of activated T cells in target organs of B6ccr2(-/
      ) splenocyte-->bm12 mice. Collectively, these findings have important clinical
      implications, as they implicate the donor non-T cell compartment as a critical
      regulator of GVHD and suggest that ccr2 expression in this cellular compartment
      may be an important molecular determinant of activation-induced cell death and
      GVHD pathogenesis.

PMID- 14568969
TI  - Transcriptional regulation of type I diabetes by NF-kappa B.
AB  - Development of type I diabetes requires coordinated expression of myriad genes
      responsible for the initiation and progression of the disease. Expression of
      these genes are regulated by a small number of transcription factors including
      the Rel/NF-kappaB family. To determine the roles of the Rel/NF-kappaB family in
      type I diabetes, we studied multiple low-dose streptozotocin-induced diabetes in
      mice deficient in either c-Rel or NF-kappaB1. We found that mice deficient in
      each of these NF-kappaB subunits were resistant to streptozotocin-induced
      diabetes. However, the mechanisms of the disease resistance may differ in
      different cases. Deficiency in c-Rel selectively reduced Th1, but not Th2
      responses, whereas NF-kappaB1 deficiency had little effect on T cell responses to
      anti-CD3 stimulation. Death of dendritic cells was accelerated in the absence of
      NF-kappaB1, whereas death of macrophages and granulocytes was affected primarily
      by c-Rel deficiency. Furthermore, Stat-1 expression was significantly reduced in
      macrophages deficient in NF-kappaB1, but not c-Rel. These results indicate that
      both c-Rel and NF-kappaB1are essential for the development of type I diabetes and
      that strategies targeting each of these subunits would be effective in preventing
      the disease.

PMID- 14568970
TI  - Polyclonal CTL responses observed in melanoma patients vaccinated with dendritic
      cells pulsed with a MAGE-3.A1 peptide.
AB  - Vaccination with mature, monocyte-derived dendritic cells (DC) pulsed with the
      MAGE-3(168-176) peptide, which is presented by HLA-A1, has been reported to
      induce tumor regressions and CTL in some advanced stage IV melanoma patients. We
      present here a precise evaluation of the level of some of these anti-MAGE-3.A1
      CTL responses and an analysis of their clonal diversity. Blood lymphocytes were
      stimulated with the MAGE-3.A1 peptide under limiting dilution conditions and
      assayed with an A1/MAGE-3 tetramer. This was followed by the cloning of the
      tetramer-positive cells and by TCR sequence analysis of the CTL clones that lysed
      targets expressing MAGE-3.A1. We also used direct ex vivo tetramer staining of
      CD8 cells, sorting, and cloning of the positive cells. In three patients who
      showed regression of some of their metastases after vaccination, CTL responses
      were observed with frequencies ranging from 7 x 10(-6) to 9 x 10(-4) of CD8(+)
      blood T lymphocytes, representing an increase of 20- to 400-fold of the
      frequencies found before immunization. A fourth patient showed neither tumor
      regression nor an anti-MAGE-3.A1 CTL response. In each of the responses, several
      CTL clones were amplified. This polyclonality contrasts with the monoclonality of
      the CTL responses observed in patients vaccinated with MAGE-3.A1 peptide or with
      an ALVAC recombinant virus coding for this antigenic peptide.

PMID- 14568971
TI  - Monoclonal anti-MAGE-3 CTL responses in melanoma patients displaying tumor
      regression after vaccination with a recombinant canarypox virus.
AB  - We have analyzed the T cell responses of HLA-A1 metastatic melanoma patients with
      detectable disease, following vaccination with a recombinant ALVAC virus, which
      bears short MAGE-1 and MAGE-3 sequences coding for antigenic peptides presented
      by HLA-A1. To evaluate the anti-MAGE CTL responses, we resorted to antigenic
      stimulation of blood lymphocytes under limiting dilution conditions, followed by
      tetramer analysis and cloning of the tetramer-positive cells. The clones were
      tested for their specific lytic ability and their TCR sequences were obtained.
      Four patients who showed tumor regression were analyzed, and an anti-MAGE-3.A1
      CTL response was observed in three of these patients. Postvaccination frequencies
      of anti-MAGE-3.A1 CTL were 3 x 10(-6), 3 x 10(-3), and 3 x 10(-7) of the blood
      CD8 T cells, respectively. These three responses were monoclonal. No anti-MAGE
      1.A1 CTL response was observed. These results indicate that, like peptide
      immunization, ALVAC immunization produces monoclonal responses. They also suggest
      that low-level antivaccine CTL responses can initiate a tumor regression process.
      Taken together, our analysis of anti-MAGE-3.A1 T cell responses following peptide
      or ALVAC vaccination shows a degree of correlation between CTL response and tumor
      regression, but firm conclusions will require larger numbers.

PMID- 14568972
TI  - Antibodies to keyhole limpet hemocyanin cross-react with an epitope on the
      polysaccharide capsule of Cryptococcus neoformans and other carbohydrates:
      implications for vaccine development.
AB  - Cryptococcus neoformans causes a life-threatening meningoencephalitis in AIDS
      patients. Mice immunized with a glycoconjugate vaccine composed of the
      glucuronoxylomannan (GXM) component of the cryptococcal capsular polysaccharide
      conjugated to tetanus toxoid produce Abs that can be either protective or
      nonprotective. Because nonprotective Abs block the efficacy of protective Abs, an
      effective vaccine must focus the Ab response on a protective epitope. Mice
      immunized with peptide mimetics of GXM conjugated to keyhole limpet hemocyanin
      (KLH) with glutaraldehyde developed Abs to GXM. However, control peptides P315
      and P24 conjugated to KLH also elicited Abs to GXM. GXM-binding Abs from mice
      immunized with P315-KLH were inhibited by KLH treated with glutaraldehyde (KLH
      g), but not by P315. Furthermore, KLH-g inhibited binding of GXM by serum of mice
      immunized with GXM-TT, indicating that glutaraldehyde treatment of KLH reveals an
      epitope(s) that cross-reacts with GXM. Vaccination with KLH-g or unmodified KLH
      elicited Abs to GXM, but did not confer protection against C. neoformans,
      suggesting the cross-reactive epitope on KLH was not protective. This was
      supported by the finding that 4H3, a nonprotective mAb, cross-reacted strongly
      with KLH-g. Sera from mice immunized with either native KLH or KLH-g cross
      reacted with several other carbohydrate Ags, many of which have been conjugated
      to KLH for vaccine development. This study illustrates how mAbs can be used to
      determine the efficacy of potential vaccines, in addition to describing the
      complexity of using KLH and glutaraldehyde in the development of vaccines to
      carbohydrate Ags.

PMID- 14568973
TI  - Gene transfer of a cell cycle modulator exerts anti-inflammatory effects in the
      treatment of arthritis.
AB  - Forced expression of a cyclin-dependent kinase inhibitor gene, p21(Cip1) in the
      synovial tissues was effective in treating animal models of rheumatoid arthritis.
      Synovial hyperplasia in the treated joints was suppressed, reflecting the
      inhibitory effect of p21(Cip1) on cell cycle progression. Additionally,
      lymphocyte infiltration, expression of inflammatory cytokines, and destruction of
      the bone and cartilage were inhibited. To determine why the cell cycle regulator
      gene exerted such anti-inflammatory effects, we investigated gene expression by
      rheumatoid synovial fibroblasts with or without the p21(Cip1) gene transferred.
      We have found that p21(Cip1) gene transfer down-regulates expression of various
      inflammatory mediators and tissue-degrading proteinases that are critically
      involved in the pathology of rheumatoid arthritis. These molecules included IL-6,
      -8, type I IL-1R (IL-1R1), monocyte chemoattractant protein-1, macrophage
      inflammatory protein-3alpha, cathepsins B and K, and matrix metalloproteinases-1
      and -3. Down-regulation of IL-1R1 by p21(Cip1) resulted in attenuated
      responsiveness to IL-1. Inhibition of the inflammatory gene expression by
      p21(Cip1) was seen even when IL-1 is absent. This IL-1R1-independent suppression
      was accompanied by reduced activity of c-Jun N-terminal kinase, which was
      associated with p21(Cip1), and inactivation of NF-kappaB and AP-1. These multiple
      regulatory effects should work in concert with the primary effect of inhibiting
      cell cycle in ameliorating the arthritis, and suggest a heretofore unexplored
      relationship between cyclin-dependent kinase inhibitor gene and inflammatory
      molecules.

PMID- 14568974
TI  - An immunomodulatory GpG oligonucleotide for the treatment of autoimmunity via the
      innate and adaptive immune systems.
AB  - Bacterial DNA and immunostimulatory CpG oligodeoxynucleotides (ODNs) activate the
      innate immune system to produce proinflammatory cytokines. Shown to be potent Th1
      like adjuvants, stimulatory CpG motifs are currently used as effective
      therapeutic vaccines for various animal models of infectious diseases, tumors,
      allergies, and autoimmune diseases. In this study, we show that the application
      of an immunomodulatory GpG ODN, with a single base switch from CpG to GpG, can
      effectively inhibit the activation of Th1 T cells associated with autoimmune
      disease. Moreover, this immunomodulatory GpG ODN suppresses the severity of
      experimental autoimmune encephalomyelitis in mice, a prototypic Th1-mediated
      animal disease model for multiple sclerosis.

PMID- 14568975
TI  - Thymic CD8+ T cell production strongly influences tumor antigen recognition and
      age-dependent glioma mortality.
AB  - For unknown reasons, advanced age remains a dominant predictor of poor clinical
      outcome for nearly all cancers. A decrease in the production of T cells by the
      thymus accompanies normal aging and parallels the age-dependent increase in
      cancer progression, but the specific impact of immunity on tumor progression in
      general is unknown. Glioblastoma multiforme (GBM), the most common primary brain
      neoplasm, is characterized by rapid age-dependent rates of progression and death.
      In this study, we show levels of CD8(+) recent thymic emigrants (RTEs) accounted
      for the prognostic power of age on clinical outcome in GBM patients. CD8(+) RTEs,
      typically a tiny proportion of CD8(+) T cells, remarkably accounted for the
      majority of tumor Ag-binding small precursor cells in PBMC from these patients
      and from healthy individuals. Large blasting tumor Ag-binding cells comprised of
      CD8(+) RTEs and phenotypically related cells were predominantly expanded
      following experimental vaccination of GBM patients. Quantification of CD8(+) RTE
      expansion in vivo correlated strongly with vaccine-elicited cytokine responses,
      and estimated numbers of expanding CD8(+) RTEs were consistent predictors of
      clinical outcome in vaccinated GBM patients. Targeted mutant (CD8beta(-/-)) mice
      specifically deficient in thymic CD8(+) T cell production uniquely displayed an
      age-specific decrease in glioma host survival as well as a strong correlation
      between host survival and thymus cellular production. These findings suggest that
      levels and function of newly produced CD8(+) T cells critically influence age
      dependent cancer mortality and exert one of the strongest known influences on GBM
      outcome by predominantly mediating clinically beneficial antitumor immune
      responses.

PMID- 14568977
TI  - Molecular mimicry between Helicobacter pylori antigens and H+, K+ --adenosine
      triphosphatase in human gastric autoimmunity.
AB  - Autoimmune gastritis and Helicobacter pylori-associated gastric atrophy develop
      through similar mechanisms involving the proton pump H+,K+-adenosine
      triphosphatase as autoantigen. Here, we report that H. pylori-infected patients
      with gastric autoimmunity harbor in vivo-activated gastric CD4+ T cells that
      recognize both H+, K+-adenosine triphosphatase and H. pylori antigens. We
      characterized the submolecular specificity of such gastric T cells and identified
      cross-reactive epitopes from nine H. pylori proteins. Cross-reactive H. pylori
      peptides induced T cell proliferation and expression of T helper type 1
      functions. We suggest that in genetically susceptible individuals, H. pylori
      infection can activate cross-reactive gastric T cells leading to gastric
      autoimmunity via molecular mimicry.

PMID- 14568978
TI  - Msh2 ATPase activity is essential for somatic hypermutation at a-T basepairs and
      for efficient class switch recombination.
AB  - Somatic hypermutation (SHM) and class switch recombination (CSR) are initiated by
      activation-induced cytidine deaminase-mediated cytidine deamination of
      immunoglobulin genes. MutS homologue (Msh) 2-/- mice have reduced A-T mutations
      and CSR. This suggests that Msh2 may play a role in repairing activation-induced
      cytidine deaminase-generated G-U mismatches. However, because Msh2 not only
      initiates mismatch repair but also has other functions, such as signaling for
      apoptosis, it is not known which activity of Msh2 is responsible for the effects
      observed, and consequently, many models have been proposed. To further dissect
      the role of Msh2 in SHM and CSR, mice with a "knockin" mutation in the Msh2 gene
      that inactivates the adenosine triphosphatase domain were examined. This mutation
      (i.e., Msh2G674A), which does not affect apoptosis signaling, allows mismatches
      to be recognized but prevents Msh2 from initiating mismatch repair. Here, we show
      that, similar to Msh2-/- mice, SHM in Msh2G674A mice is biased toward G-C
      mutations. However, CSR is partially reduced, and switch junctions are more
      similar to those of postmeiotic segregation 2-/- mice than to Msh2-/- mice. These
      results indicate that Msh2 adenosine triphosphatase activity is required for A-T
      mutations, and suggest that Msh2 has more than one role in CSR.

PMID- 14568979
TI  - Human decidual natural killer cells are a unique NK cell subset with
      immunomodulatory potential.
AB  - Natural killer cells constitute 50-90% of lymphocytes in human uterine decidua in
      early pregnancy. Here, CD56(bright) uterine decidual NK (dNK) cells were compared
      with the CD56(bright) and CD56(dim) peripheral NK cell subsets by microarray
      analysis, with verification of results by flow cytometry and RT-PCR. Among the
      approximately 10,000 genes studied, 278 genes showed at least a threefold change
      with P < or = 0.001 when comparing the dNK and peripheral NK cell subsets, most
      displaying increased expression in dNK cells. The largest number of these encoded
      surface proteins, including the unusual lectinlike receptors NKG2E and Ly-49L,
      several killer cell Ig-like receptors, the integrin subunits alpha(D), alpha(X),
      beta1, and beta5, and multiple tetraspanins (CD9, CD151, CD53, CD63, and TSPAN
      5). Additionally, two secreted proteins, galectin-1 and progestagen-associated
      protein 14, known to have immunomodulatory functions, were selectively expressed
      in dNK cells.

PMID- 14568980
TI  - Elimination in vivo of developing T cells by natural killer cells.
AB  - Natural killer cells gauge the absence of self class I MHC on susceptible target
      cells by means of inhibitory receptors such as members of the Ly49 family. To
      initiate killing by natural killer cells, a lack of inhibitory signals must be
      accompanied by the presence of activating ligands on the target cell. Although
      natural killer cell-mediated rejection of class I MHC-deficient bone marrow (BM)
      grafts is a matter of record, little is known about the targeting in vivo of
      specific cellular subsets by natural killer cells. We show here that development
      of class I MHC-negative thymocytes is delayed as a result of natural killer cell
      toxicity after grafting of a class I MHC-positive host with class I MHC-negative
      BM. Double positive thymocytes that persist in the presence of natural killer
      cells display an unusual T cell receptor-deficient phenotype, yet nevertheless
      give rise to single positive thymocytes and yield mature class I MHC-deficient
      lymphocytes that accumulate in the class I MHC-positive host. The resulting class
      I MHC-deficient CD8 T cells are functional and upon activation remain susceptible
      to natural killer cell toxicity in vivo. Reconstitution of class I MHC-deficient
      BM precursors with H2-K(b) by retroviral transduction fully restores normal
      thymic development.

PMID- 14568981
TI  - Intracellular recognition of lipopolysaccharide by toll-like receptor 4 in
      intestinal epithelial cells.
AB  - Toll-like receptor (TLR)4 has recently been shown to reside in the Golgi
      apparatus of intestinal crypt epithelial m-ICcl2 cells, colocalizing with
      internalized lipopolysaccharide (LPS). Here we demonstrate that disruption of the
      integrity of the Golgi apparatus significantly reduced LPS-mediated nuclear
      factor kappaB activation. Also, the TLR4 adaptor protein MyD88 and the
      serine/threonine kinase IRAK-1 were rapidly recruited to the Golgi apparatus upon
      stimulation. LPS-mediated activation required lipid raft formation and intact
      clathrin-dependent internalization. In contrast to macrophages, prevention of
      ligand internalization by use of LPS-coated beads significantly impaired
      recognition by epithelial cells. The localization of TLR4 to the Golgi apparatus
      was abrogated by expression of a genetically modified form of the TLR4 binding
      chaperone gp96. Thus, our data provide evidence that in contrast to the situation
      in macrophages, LPS recognition in intestinal epithelial cells may occur in the
      Golgi apparatus and require LPS internalization.

PMID- 14568982
TI  - A critical role for OX40 in T cell-mediated immunopathology during lung viral
      infection.
AB  - Respiratory infections are the third leading cause of death worldwide. Illness is
      caused by pathogen replication and disruption of airway homeostasis by excessive
      expansion of cell numbers. One strategy to prevent lung immune-mediated damage
      involves reducing the cellular burden. To date, antiinflammatory strategies have
      affected both antigen-specific and naive immune repertoires. Here we report a
      novel form of immune intervention that specifically targets recently activated T
      cells alone. OX40 (CD134) is absent on naive T cells but up-regulated 1-2 d after
      antigen activation. OX40-immunoglobulin fusion proteins block the interaction of
      OX40 with its ligand on antigen-presenting cells and eliminate weight loss and
      cachexia without preventing virus clearance. Reduced proliferation and enhanced
      apoptosis of lung cells accompanied the improved clinical phenotype. Manipulation
      of this late costimulatory pathway has clear therapeutic potential for the
      treatment of dysregulated lung immune responses.

PMID- 14568983
TI  - Lipopolysaccharide or whole bacteria block the conversion of inflammatory
      monocytes into dendritic cells in vivo.
AB  - Monocytes can develop into dendritic cells (DCs) that migrate to lymph nodes
      (LNs) and present antigens to T cells. However, we find that this differentiation
      is blocked when monocytes accumulate subcutaneously in response to bacteria or
      lipopolysaccharide (LPS). The inhibition of DC differentiation is mediated by the
      bacteria and in conjunction with inflammatory cells recruited at the site of
      injection. Inhibition of migratory DC development was reversed in Toll-like
      receptor (TLR)4-mutated mice when LPS, but not whole bacteria, was injected,
      suggesting that TLR4 is one but not the only mediator of the inhibition. The
      block imposed by bacteria was partly relieved by the absence of interleukin (IL)
      12 p40, but not by individual absence of several cytokines involved in DC
      differentiation or in inflammation, i.e., IL-6, IL-10, IL-12 p35, and interferon
      gamma. Consistent with the inability of monocytes to yield migrating DCs, and the
      finding that other DCs had limited access to particulate or bacterial antigens,
      these antigens were weakly presented to T cells in the draining LN. These results
      illustrate that bacteria-associated signals can have a negative regulatory role
      on adaptive immunity and that local innate responses for containment of
      infectious bacteria can at least initially supersede development of adaptive
      responses.

PMID- 14568984
TI  - Differential regulation of interleukin (IL)-12 p35 and p40 gene expression and
      interferon (IFN)-gamma-primed IL-12 production by IFN regulatory factor 1.
AB  - Interleukin (IL)-12 is a heterodimeric cytokine consisting of the p40 and p35
      chains encoded on separate chromosomes. Coordinated expression of the two
      constituent genes is crucial for appropriate immune responses in timing,
      location, and magnitude. Interferon (IFN)-gamma priming of IL-12 production by
      macrophages represents an important physiological process in vivo for escalated
      cellular response to microbial infections. We provide evidence that IFN
      regulatory factor (IRF)-1-deficient macrophages have a selective impairment in
      mRNA synthesis of IL-12 p35 but not the p40 gene, and a strong deficiency in the
      production of IL-12 p70 but not p40. We demonstrate that the levels of IL-12 p35
      protein stimulated by IFN-gamma and lipopolysaccharide (LPS) correspond to those
      of its mRNA, and that the nuclear factor kappaB signaling pathway is essential
      for the induction of IL-12 p35 transcription by LPS. IRF-1 plays a major role in
      the transcriptional activation of the IL-12 p35 gene, but not of the p40 gene, by
      physically interacting with an inverted IRF element within the IL-12 p35 promoter
      upon IFN-gamma activation. Moreover, IRF-1-mediated transcriptional activation of
      the p35 promoter requires the cooperation of two adjacent Sp1 elements. Thus, IRF
      1 acts as a critical component of IFN-gamma signaling in the selective activation
      of IL-12 p35 transcription in synergy with LPS-mediated events.

PMID- 14568985
TI  - Thrombospondin 1 is an autocrine negative regulator of human dendritic cell
      activation.
AB  - Thrombospondin 1 (TSP) elicits potent antiinflammatory activities in vivo, as
      evidenced by persistent, multiorgan inflammation in TSP null mice. Herein, we
      report that DCs represent an abundant source of TSP at steady state and during
      activation. Human monocyte-derived immature dendritic cells (iDCs) spontaneously
      produce TSP, which is strongly enhanced by PGE2 and to a lesser extent by
      transforming growth factor (TGF) beta, two soluble mediators secreted by
      macrophages after engulfment of damaged tissues. Shortly after activation via
      danger signals, DCs transiently produce interleukin (IL) 12 and tumor necrosis
      factor (TNF) alpha, thereby eliciting protective and inflammatory immune
      responses. Microbial stimuli increase TSP production, which is further enhanced
      by IL-10 or TGF-beta. The endogenous TSP produced during early DC activation
      negatively regulates IL-12, TNF-alpha, and IL-10 release through its interactions
      with CD47 and CD36. After prolonged activation, DCs extinguish their cytokine
      synthesis and become refractory to subsequent stimulation, thereby favoring the
      return to steady state. Such "exhausted" DCs continue to release TSP but not IL
      10. Disrupting TSP-CD47 interactions during their restimulation restores their
      cytokine production. We conclude that DC-derived TSP serves as a previously
      unappreciated negative regulator contributing to arrest of cytokine production,
      further supporting its fundamental role in vivo in the active resolution of
      inflammation and maintenance of steady state.

PMID- 14568986
TI  - Poor-risk testicular cancer and high-dose chemotherapy.

PMID- 14568987
TI  - Long-term results of first-line sequential high-dose etoposide, ifosfamide, and
      cisplatin chemotherapy plus autologous stem cell support for patients with
      advanced metastatic germ cell cancer: an extended phase I/II study of the German
      Testicular Cancer Study Group.
AB  - PURPOSE: Patients with disseminated germ cell cancer and poor prognosis
      (International Germ Cell Cancer Collaborative Group [IGCCCG] classification)
      achieve only a 45% to 50% long-term survival by standard chemotherapy. First-line
      high-dose chemotherapy might be able to improve the result. This analysis reports
      toxicity and long-term results of a large phase I/II study of sequential high
      dose etoposide, ifosfamide, and cisplatin (VIP) in patients with advanced germ
      cell tumors. PATIENTS AND METHODS: Between July 1993 and November 1999, 221
      patients with either Indiana "advanced disease" (n = 39) or IGCCCG "poor
      prognosis" criteria (n = 182) received one cycle of VIP followed by three to four
      sequential cycles of high-dose VIP chemotherapy plus stem cell support, every 3
      weeks, at six consecutive dose levels. RESULTS: Dose limiting toxicity occurred
      at level 8 (100 mg/m2 cisplatinum, 1750 mg/m2 etoposide, 12 g/m2 ifosfamide) with
      grade 4 mucositis (three of eight patients), grade 3 CNS toxicity (one of eight
      patients), grade 4 renal toxicity (one of eight patients), and prolonged
      granulocytopenia (one of eight patients). After 4-year median follow-up,
      progression-free survival and disease-specific survival rates in the poor
      prognosis subgroup were 69% and 79% at 2 years and 68% and 73% at 5 years, with
      76% for gonadal/retroperitoneal versus 67% for mediastinal primaries. Severe
      toxicity included treatment related death (4%), treatment-related acute myeloid
      leukemia (1%), long-term impared renal function (3%), chronic renal failure (1%),
      and persistent grade 2-3 neuropathy (5%). CONCLUSION: Repetitive cycles of high
      dose VIP with peripheral stem cell support can be successfully applied in a
      multicenter setting. Dose level 6 with cisplatin 100 mg/m2, etoposide 1500 mg/m2,
      and ifosfamide 10 g/m2 is recommended for further investigation in randomized
      trials. An ongoing randomized trial within the European Organization for Research
      and Treatment of Cancer evaluates this protocol against four cycles of standard
      cisplatin, etoposide, and bleomycin.

PMID- 14568988
TI  - Disruption of TGF-beta signaling in T cells accelerates atherosclerosis.
AB  - Increasing evidence suggests that atherosclerosis is an inflammatory disease
      promoted by hypercholesterolemia. The role of adaptive immunity has been
      controversial, however. We hypothesized that proatherogenic T cells are
      controlled by immunoregulatory cytokines. Among them, TGF-beta has been implied
      in atherosclerosis, but its mechanism of action remains unclear. We crossed
      atherosclerosis-prone ApoE-knockout mice with transgenic mice carrying a dominant
      negative TGF-beta receptor II in T cells. The ApoE-knockout mice with disrupted
      TGF-beta signaling in T cells exhibited a sixfold increase in aortic lesion
      surface area, a threefold increase in aortic root lesion size, and a 125-fold
      increase in aortic IFN-gamma mRNA when compared with age-matched ApoE-knockout
      littermates. When comparing size-matched lesions, those of mice with T cell
      specific blockade of TGF-beta signaling displayed increased T cells, activated
      macrophages, and reduced collagen, consistent with a more vulnerable phenotype.
      Ab's to oxidized LDL, circulating T cell cytokines, and spleen T cell activity
      were all increased in ApoE-knockout mice with dominant negative TGF-beta
      receptors in T cells. Taken together, these results show that abrogation of TGF
      beta signaling in T cells increases atherosclerosis and suggest that TGF-beta
      reduces atherosclerosis by dampening T cell activation. Inhibition of T cell
      activation may therefore represent a strategy for antiatherosclerotic therapy.

PMID- 14568989
TI  - Herpes simplex virus triggers activation of calcium-signaling pathways.
AB  - The cellular pathways required for herpes simplex virus (HSV) invasion have not
      been defined. To test the hypothesis that HSV entry triggers activation of Ca2+
      signaling pathways, the effects on intracellular calcium concentration ([Ca2+]i)
      after exposure of cells to HSV were examined. Exposure to virus results in a
      rapid and transient increase in [Ca2+]i. Pretreatment of cells with
      pharmacological agents that block release of inositol 1,4,5-triphosphate (IP3)
      sensitive endoplasmic reticulum stores abrogates the response. Moreover,
      treatment of cells with these pharmacological agents inhibits HSV infection and
      prevents focal adhesion kinase (FAK) phosphorylation, which occurs within 5 min
      after viral infection. Viruses deleted in glycoprotein L or glycoprotein D, which
      bind but do not penetrate, fail to induce a [Ca2+]i response or trigger FAK
      phosphorylation. Together, these results support a model for HSV infection that
      requires activation of IP3-responsive Ca2+-signaling pathways and that is
      associated with FAK phosphorylation. Defining the pathway of viral invasion may
      lead to new targets for anti-viral therapy.

PMID- 14568990
TI  - Role of the pleckstrin homology domain of PLCgamma1 in its interaction with the
      insulin receptor.
AB  - A thiol-reactive membrane-associated protein (TRAP) binds covalently to the
      cytoplasmic domain of the human insulin receptor (IR) beta-subunit when cells are
      treated with the homobifunctional cross-linker reagent 1,6-bismaleimidohexane.
      Here, TRAP was found to be phospholipase C gamma1 (PLCgamma1) by mass
      spectrometry analysis. PLCgamma1 associated with the IR both in cultured cell
      lines and in a primary culture of rat hepatocytes. Insulin increased PLCgamma1
      tyrosine phosphorylation at Tyr-783 and its colocalization with the IR in
      punctated structures enriched in cortical actin at the dorsal plasma membrane.
      This association was found to be independent of PLCgamma1 Src homology 2 domains,
      and instead required the pleckstrin homology (PH)-EF-hand domain. Expression of
      the PH-EF construct blocked endogenous PLCgamma1 binding to the IR and inhibited
      insulin-dependent phosphorylation of mitogen-activated protein kinase (MAPK), but
      not AKT. Silencing PLCgamma1 expression using small interfering RNA markedly
      reduced insulin-dependent MAPK regulation in HepG2 cells. Conversely,
      reconstitution of PLCgamma1 in PLCgamma1-/- fibroblasts improved MAPK activation
      by insulin. Our results show that PLCgamma1 is a thiol-reactive protein whose
      association with the IR could contribute to the activation of MAPK signaling by
      insulin.

PMID- 14568991
TI  - Akt activation disrupts mammary acinar architecture and enhances proliferation in
      an mTOR-dependent manner.
AB  - Activation of the serine/threonine kinase Akt/PKB positively impacts on three
      cellular processes relevant to tumor progression: proliferation, survival, and
      cell size/growth. Using a three-dimensional culture model of MCF-10A mammary
      cells, we have examined how Akt influences the morphogenesis of polarized
      epithelial structures. Activation of a conditionally active variant of Akt
      elicits large, misshapen structures, which primarily arise from the combined
      effects of Akt on proliferation and cell size. Importantly, Akt activation
      amplifies proliferation during the early stages of morphogenesis, but cannot
      overcome signals suppressing proliferation in late-stage cultures. Akt also
      cooperates with oncoproteins such as cyclin D1 or HPV E7 to promote proliferation
      and morphogenesis in the absence of growth factors. Pharmacological inhibition of
      the Akt effector, mammalian target of rapamycin (mTOR), with rapamycin prevents
      the morphological disruption elicited by Akt activation, including its effect on
      cell size and number, and the cooperative effect of Akt on oncogene-driven
      proliferation, indicating that mTOR function is required for the multiple
      biological effects of Akt activation during morphogenesis.

PMID- 14568992
TI  - Loss of keratin 6 (K6) proteins reveals a function for intermediate filaments
      during wound repair.
AB  - The ability to heal wounds is vital to all organisms. In mammalian tissues,
      alterations in intermediate filament (IF) gene expression represent an early
      reaction of cells surviving injury. We investigated the role of keratin IFs
      during the epithelialization of skin wounds using a keratin 6alpha and 6beta
      (K6alpha/K6beta)-null mouse model. In skin explant culture, null keratinocytes
      exhibit an enhanced epithelialization potential due to increased migration. The
      extent of the phenotype is strain dependent, and is accompanied by alterations in
      keratin IF and F-actin organization. However, in wounded skin in vivo, null
      keratinocytes rupture as they attempt to migrate under the blood clot. Fragility
      of the K6alpha/K6beta-null epidermis is confirmed when applying trauma to
      chemically treated skin. We propose that the alterations in IF gene expression
      after tissue injury foster a compromise between the need to display the cellular
      pliability necessary for timely migration and the requirement for resilience
      sufficient to withstand the rigors of a wound site.

PMID- 14568993
TI  - NAADP mobilizes Ca2+ from a thapsigargin-sensitive store in the nuclear envelope
      by activating ryanodine receptors.
AB  - Ca2+ release from the envelope of isolated pancreatic acinar nuclei could be
      activated by nicotinic acid adenine dinucleotide phosphate (NAADP) as well as by
      inositol 1,4,5-trisphosphate (IP3) and cyclic ADP-ribose (cADPR). Each of these
      agents reduced the Ca2+ concentration inside the nuclear envelope, and this was
      associated with a transient rise in the nucleoplasmic Ca2+ concentration. NAADP
      released Ca2+ from the same thapsigargin-sensitive pool as IP3. The NAADP action
      was specific because, for example, nicotineamide adenine dinucleotide phosphate
      was ineffective. The Ca2+ release was unaffected by procedures interfering with
      acidic organelles (bafilomycin, brefeldin, and nigericin). Ryanodine blocked the
      Ca2+-releasing effects of NAADP, cADPR, and caffeine, but not IP3. Ruthenium red
      also blocked the NAADP-elicited Ca2+ release. IP3 receptor blockade did not
      inhibit the Ca2+ release elicited by NAADP or cADPR. The nuclear envelope
      contains ryanodine and IP3 receptors that can be activated separately and
      independently; the ryanodine receptors by either NAADP or cADPR, and the IP3
      receptors by IP3.

PMID- 14568995
TI  - Dietary sodium loading increases arterial pressure in afferent renal-denervated
      rats.
AB  - In rats fed high sodium diet, increasing renal pelvic pressure > or =3 mm Hg
      activates renal mechanosensory nerves, resulting in a renorenal reflex-induced
      increase in urinary sodium excretion. The low activation threshold of the renal
      mechanosensory nerves suggests a role for natriuretic renorenal reflexes in the
      regulation of arterial pressure and sodium balance. If so, interruption of the
      afferent renal innervation by dorsal rhizotomy (DRX) at T9-L1 would impair
      urinary sodium excretion and/or increase arterial pressure during high dietary
      sodium intake. DRX and sham-DRX rats were fed either a high or a normal sodium
      diet for 3 weeks. Mean arterial pressure measured in conscious rats was higher in
      DRX than in sham-DRX rats fed a high sodium diet, 130+/-2 vs 100+/-3 mm Hg
      (P<0.01). However, mean arterial pressure was similar in DRX and sham-DRX rats
      fed a normal sodium diet, 115+/-1 and 113+/-1 mm Hg, respectively. Steady-state
      urinary sodium excretion was similar in DRX and sham-DRX rats on high (17.9+/-2.2
      and 16.4+/-1.8 mmol/24 h, respectively) and normal (4.8+/-0.3 and 5.0+/-0.4
      mmol/24 h, respectively) sodium diets. Studies in anesthetized rats showed a lack
      of an increase in afferent renal nerve activity in response to increased renal
      pelvic pressure and impaired prostaglandin E2-mediated release of substance P
      from the renal pelvic nerves in DRX rats fed either a high or a normal sodium
      diet, suggesting that DRX resulted in decreased responsiveness of peripheral
      renal sensory nerves. In conclusion, when the afferent limb of the renorenal
      reflex is interrupted, a high sodium diet results in increased arterial pressure
      to facilitate the natriuresis and maintenance of sodium balance.

PMID- 14568994
TI  - Impairment of LTD and cerebellar learning by Purkinje cell-specific ablation of
      cGMP-dependent protein kinase I.
AB  - The molecular basis for cerebellar plasticity and motor learning remains
      controversial. Cerebellar Purkinje cells (PCs) contain a high concentration of
      cGMP-dependent protein kinase type I (cGKI). To investigate the function of cGKI
      in long-term depression (LTD) and cerebellar learning, we have generated
      conditional knockout mice lacking cGKI selectively in PCs. These cGKI mutants had
      a normal cerebellar morphology and intact synaptic calcium signaling, but
      strongly reduced LTD. Interestingly, no defects in general behavior and motor
      performance could be detected in the LTD-deficient mice, but the mutants
      exhibited an impaired adaptation of the vestibulo-ocular reflex (VOR). These
      results indicate that cGKI in PCs is dispensable for general motor coordination,
      but that it is required for cerebellar LTD and specific forms of motor learning,
      namely the adaptation of the VOR.

PMID- 14568996
TI  - Suppression of gamma-melanocyte-stimulating hormone secretion is accompanied by
      salt-sensitive hypertension in the rat.
AB  - Gamma-melanocyte-stimulating hormone (gamma-MSH) is a natriuretic peptide derived
      from proopiomelanocortin (POMC) in the pituitary neurointermediate lobe (NIL);
      its plasma concentration in rats doubles after ingestion of a high (HSD; 8% NaCl)
      compared with a low sodium diet (LSD; 0.07%). Because NIL function is regulated
      through dopaminergic pathways, we asked whether dopaminergic stimulation with
      bromocriptine (5 mg/kg IP daily for 1 week) or inhibition with haloperidol (5
      mg/kg IP for 1 week) alters the gamma-MSH response to a HSD. In vehicle-treated
      rats, plasma gamma-MSH and NIL gamma-MSH content on the HSD were both markedly
      elevated over values in rats on the LSD (P<0.001); no difference in mean arterial
      pressure (MAP) occurred. In haloperidol-treated rats on the LSD, both plasma
      gamma-MSH and NIL gamma-MSH content were greater than in vehicle-treated rats
      (P<0.05) and did not increase further on the HSD; MAP was also no different. In
      bromocriptine-treated rats, neither plasma gamma-MSH nor NIL gamma-MSH content
      increased on the HSD versus LSD, and MAP was markedly elevated on the HSD (132+/
      3 versus 106+/-3 mm Hg, P<0.001). Intravenous infusion of gamma-MSH (0.4
      pmol/min) to bromocriptine-treated rats on the HSD restored plasma gamma-MSH
      concentration to a level appropriate for the HSD and lowered MAP from 131+/-6 to
      108+/-5 mm Hg (P<0.01). These results demonstrate that the increases in NIL
      content and plasma concentration of gamma-MSH normally occurring during ingestion
      of the HSD are prevented by dopaminergic suppression of NIL function. This
      results in deficiency of gamma-MSH on the HSD and is accompanied by elevated
      blood pressure, which is corrected by infusion of the peptide. gamma-MSH may be
      an important component in the normal response to a HSD; interruption of this
      response leads to salt-sensitive hypertension.

PMID- 14568997
TI  - Gene therapy with human tissue kallikrein reduces hypertension and
      hyperinsulinemia in fructose-induced hypertensive rats.
AB  - This study investigates gene therapy with human tissue kallikrein as a treatment
      for fructose-induced hypertension in rats. Hypertension was induced by addition
      of 10% fructose to drinking water. Fructose-fed rats also had increased serum
      insulin and triglycerides, decreased urine osmolarity, increased urine volume and
      endothelin-1, and increased aortic endothelin-1, endothelin-A receptor, and
      angiotensin II receptor type 1 mRNA levels. Fructose-induced hypertensive and
      control rats were injected intravenously with a construct containing the human
      tissue kallikrein cDNA. Two weeks after injection of hypertensive rats, systolic
      blood pressure and serum insulin levels normalized, urine osmolarity increased,
      urine endothelin-1 levels decreased, and aortic endothelin-1, endothelin-A
      receptor, and angiotensin II receptor type 1 mRNA levels decreased. In contrast,
      injection of the human tissue kallikrein cDNA had minimal effect on blood
      pressure or insulin levels in control rats. These results suggest that gene
      therapy with human tissue kallikrein may have potential as a treatment for
      hypertension and associated insulin resistance. Moreover, our data suggest that
      the beneficial effects of human tissue kallikrein on these parameters are
      associated with changes in endothelin-1, endothelin-A receptor, and angiotensin
      II receptor type 1 expression.

PMID- 14568998
TI  - Chronic administration of adrenomedullin attenuates transition from left
      ventricular hypertrophy to heart failure in rats.
AB  - Acute administration of adrenomedullin (AM) exerts beneficial hemodynamic, renal,
      and neurohormonal effects in heart failure (HF). However, chronic effects of AM
      administration on HF remain unknown. This study sought to examine the effect of
      chronic infusion of AM on progression of HF in rat. Human recombinant AM was
      administered by osmotic minipump for 7 weeks in the HF model of Dahl salt
      sensitive rats. The effect was compared with vehicle and diuretic treatment
      group. Chronic AM infusion significantly decreased left ventricular end-diastolic
      pressure, right ventricular systolic pressure, right atrial pressure, and left
      ventricular weight/body weight (P<0.01 for all). AM significantly attenuated the
      increase in circulating renin-aldosterone, endogenous rat AM, and atrial
      natriuretic peptide levels (P<0.01 for all). AM also inhibited the myocardial
      tissue levels of angiotensin II and atrial and brain natriuretic peptide (P<0.01
      for all). These changes were associated with the improvement of cardiac output
      and systemic vascular resistance (both P<0.05). Furthermore, AM improved left
      ventricular end-systolic elastance (P<0.01). These improvements were greater in
      the AM than in the diuretic group, although both drugs similarly decreased
      systolic blood pressure and increased urinary sodium excretion. Kaplan-Meier
      survival analysis showed that AM significantly prolonged survival time compared
      with diuretic (P<0.05) and vehicle (P<0.01) treatment groups. These results
      suggest that endogenous AM plays a compensatory role in HF and that chronic AM
      infusion attenuates progression of left ventricular dysfunction and improves
      survival, at least in part, through inhibition of circulating and myocardial
      neurohormonal activation.

PMID- 14568999
TI  - Effects of hypertension and obesity on the sympathetic activation of heart
      failure patients.
AB  - Previous studies have shown that congestive heart failure is characterized by
      sympathetic and reflex dysfunctions. Whether these alterations are potentiated in
      the presence of obesity and hypertension, two conditions that also display
      neuroadrenergic abnormalities and markedly increase the risk of heart failure, is
      unknown. In 14 healthy control subjects (C; age, 55.1+/-3.0 years; mean+/-SEM),
      13 lean hypertensive subjects (H), 15 obese normotensive subjects (O), 14 lean
      normotensive subjects with congestive heart failure (CHF, New York Heart
      Association class II), 14 lean hypertensive subjects with CHF (CHFH), 14 obese
      normotensive subjects with CHF (CHFO), and 13 obese hypertensive subjects with
      CHF (CHFOH), all age-matched with C, we measured mean blood pressure (Finapres),
      heart rate (ECG), and muscle sympathetic nerve traffic (MSNA, microneurography)
      at rest and during baroreflex testing. Compared with C, body mass index was
      similarly increased in O, CHFO, and CHFOH, whereas mean blood pressure was
      similarly increased in HF, CHFH, and CHFOH, and left ventricular ejection
      fraction (echocardiography) was similarly reduced in CHF, CHFH, CHFO and CHFOH.
      Compared with C, MSNA was significantly increased in O, H, and CHF (43.0+/-2.2
      versus 54.1+/-2.8, 53.1+/-2.5, and 57.4+/-2.8 bursts/100 heart beats, P<0.01).
      When O or H was combined with CHF, the MSNA increase was significantly more
      pronounced and maximal when O and H were concomitantly associated with CHF.
      Baroreflex sensitivity was reduced in O and H, with a further reduction in CHF
      and a minimal value in CHFOH. These data show that the sympathetic activation
      characterizing CHF is markedly potentiated when O and H alone or combined
      together are associated with a low cardiac output state and that this may depend
      on an arterial baroreflex impairment.

PMID- 14569000
TI  - Is very high sympathetic tone in heart failure a result of keeping bad company?

PMID- 14569001
TI  - Renal effects of omapatrilat and captopril in salt-loaded, nitric oxide-deficient
      rats.
AB  - Inhibition of nitric oxide synthases causes systemic hypertension and renal
      injury in rats. Our objective was to examine whether omapatrilat, a vasopeptidase
      inhibitor that inhibits both angiotensin-converting enzyme (ACE) and neutral
      endopeptidase, could induce better regression of renal injury than ACE inhibitor
      alone. Ten groups of rats were studied. They were fed either a normal (0.8% NaCl)
      or a high (4% NaCl) sodium diet. Eight of these groups received NG-nitro-L
      arginine methyl ester (L-NAME, 20 mg x kg(-1) x d(-1)) in their drinking water.
      After 4 weeks, 1 group on each diet was killed and considered the L-NAME group,
      whereas the others received L-NAME alone, captopril (200 mg x kg(-1) x d(-1))
      plus L-NAME, or omapatrilat (80 mg x kg(-1) x d(-1)) plus L-NAME for 4 additional
      weeks. In rats receiving L-NAME alone for 8 weeks, the mortality rate was
      approximately 90%, irrespective of the diet. In contrast, all rats survived in
      the captopril and the omapatrilat groups. In rats fed a normal-sodium diet,
      captopril and omapatrilat normalized systolic blood pressure and induced a
      complete regression of renal injury. Creatinine clearance and proteinuria were
      also normalized. In the high-sodium-diet groups, both treatments were less
      efficient: blood pressure remained elevated, and the regression of renal fibrosis
      was only partial. Although proteinuria decreased significantly with captopril or
      omapatrilat, creatinine clearance remained lower than in the controls. These
      results demonstrate that, in nitric oxide-deficient rats fed a normal-sodium
      diet, ACE and vasopeptidase inhibitors exhibit a marked renoprotective effect,
      whereas these treatments are less efficient in rats fed a high-sodium diet.

PMID- 14569002
TI  - Role of androgens in mediating renal injury in aging SHR.
AB  - Men have an increased risk of cardiovascular and renal diseases and develop
      greater renal injury despite similar levels of blood pressure when compared with
      women. The mechanisms responsible for this predisposition are unknown. Using the
      spontaneously hypertensive rat (SHR), we have found that androgens play an
      important role in the development of hypertension in young male SHR. However, the
      role that androgens play in age-related renal injury and dysfunction in SHR is
      unknown. Our hypothesis was that despite reductions in serum testosterone with
      age, androgens mediate renal injury and dysfunction in male SHR. Male SHR were
      castrated at 8 months of age, studied at 18 months of age, and compared with age
      matched, intact males and young intact males (4 months). Serum testosterone was
      reduced by 30% in aging males compared with young SHR. With castration, blood
      pressure (mean arterial pressure [MAP]) was decreased by >20 mm Hg compared with
      old males, glomerular filtration rate (GFR) was increased by >35%, and renal
      vascular resistance (RVR) was reduced by >40%. MAP, GFR, and RVR in castrated,
      old males were similar to values in young males. With castration, glomerular
      sclerosis was reversed and proteinuria was also decreased by >80% when compared
      with old intact males. In addition, in castrated old males, plasma renin activity
      was decreased by 30% compared with old males and by 60% compared with young rats.
      The data support the hypothesis that despite a reduction in testosterone with
      age, androgens play an important role in age-related renal injury and dysfunction
      in SHR.

PMID- 14569003
TI  - Distinct roles of Bazooka and Stardust in the specification of Drosophila
      photoreceptor membrane architecture.
AB  - Photoreceptors form during Drosophila pupal development and acquire elaborate
      membrane structures, including the rhabdomeres and stalk membranes. Here, we show
      that the development of these cellular structures involves two distinct
      processes: the establishment of apical-basal polarity that requires Bazooka
      (Baz), and the regionalization of apical membrane into stalk membranes and
      rhabdomeres that requires Stardust (Sdt). In the absence of Baz, the apical-basal
      polarity is compromised in early pupal photoreceptors, and no identifiable apical
      membrane domain is formed. Sdt, in contrast, plays a more limited role in apical
      basal polarity but is essential for the proper localization of transmembrane
      protein Crumbs (Crb), known to be required in the biogenesis of stalk membrane.
      Loss of Sdt causes strong defects in stalk membrane and rhabdomere resembling crb
      mutant phenotype. Thus, proteins required for establishing the early embryonic
      epithelial polarity are used later for the morphogenesis of photoreceptors, with
      Baz and Sdt functioning in different aspects of the formation of the apical-basal
      cellular architecture.

PMID- 14569004
TI  - A plant virus replication system to assay the formation of RNA pseudotriloop
      motifs in RNA-protein interactions.
AB  - A pseudotriloop is formed by transloop base pairing between the first (5') and
      the fifth nucleotide in a hexanucleotide RNA loop ("hexaloop") to subtend a
      triloop of nucleotides 2-4. This structure has been found in hairpins involved in
      the regulation of iron metabolism in mammalian cells and in transcription of
      plant virus subgenomic RNA. Several hexaloop hairpins, including HIV
      transactivation-responsive element and hepatitis B virus , potentially adopt a
      pseudotriloop conformation. Here we show that an RNA plant virus whose
      replication depends on a conventional triloop hairpin can be used to verify the
      existence of pseudotriloop structures in vivo. Our data suggest that the
      pseudotriloop may represent a common motif in RNA-protein recognition.

PMID- 14569005
TI  - Dynamic structures in Escherichia coli: spontaneous formation of MinE rings and
      MinD polar zones.
AB  - In Escherichia coli, division site selection is regulated in part by the Min
      protein system. Oscillations of the Min proteins from pole to pole every
      approximately 40 sec have been revealed by in vivo studies of GFP fusions. The
      dynamic oscillatory structures produced by the Min proteins, including a ring of
      MinE protein, compact polar zones of MinD, and zebra-striped oscillations in
      filamentous cells, remain unexplained. We show that the Min oscillations,
      including mutant phenotypes, can be accounted for by in vitro-observed
      interactions involving MinD and MinE, with a crucial role played by the rate of
      nucleotide exchange. Recent discoveries suggest that protein oscillations may
      play a general role in proper chromosome and plasmid partitioning.

PMID- 14569006
TI  - Antiviral immune responses in gene-targeted mice expressing the immunoglobulin
      heavy chain of virus-neutralizing antibodies.
AB  - Two gene-targeted immunoglobulin heavy chain transgenic mouse strains, TgH(KL25)
      and TgH(VI10), expressing neutralizing specificities for lymphocytic
      choriomeningitis virus and vesicular stomatitis virus, respectively, have been
      generated. Three days after lymphocytic choriomeningitis virus infection,
      TgH(KL25) mice showed a thymus-independent neutralizing IgM response followed by
      thymus-dependent (TD) IgG. In contrast, WT mice mounted only a TD IgG response
      around day 80. These observations indicated that not only structural properties
      of the virus but also immunological parameters such as the frequency of B cells
      were indicative for the induction of thymus-independent versus TD Ig responses.
      Naive vesicular stomatitis virusspecific Ig heavy chain transgenic mice displayed
      greatly elevated natural antibody titers. However, despite these high naive
      titers, de novo activation of naive CD4+ T and B cells was not blocked.
      Therefore, B cells giving rise to natural antibodies do not participate in virus
      induced antibody responses.

PMID- 14569008
TI  - Biodiversity as spatial insurance in heterogeneous landscapes.
AB  - The potential consequences of biodiversity loss for ecosystem functioning and
      services at local scales have received considerable attention during the last
      decade, but little is known about how biodiversity affects ecosystem processes
      and stability at larger spatial scales. We propose that biodiversity provides
      spatial insurance for ecosystem functioning by virtue of spatial exchanges among
      local systems in heterogeneous landscapes. We explore this hypothesis by using a
      simple theoretical metacommunity model with explicit local consumer-resource
      dynamics and dispersal among systems. Our model shows that variation in dispersal
      rate affects the temporal mean and variability of ecosystem productivity strongly
      and nonmonotonically through two mechanisms: spatial averaging by the
      intermediate-type species that tends to dominate the landscape at high dispersal
      rates, and functional compensations between species that are made possible by the
      maintenance of species diversity. The spatial insurance effects of species
      diversity are highest at the intermediate dispersal rates that maximize local
      diversity. These results have profound implications for conservation and
      management. Knowledge of spatial processes across ecosystems is critical to
      predict the effects of landscape changes on both biodiversity and ecosystem
      functioning and services.

PMID- 14569007
TI  - Identification of T cell-signaling pathways that stimulate latent HIV in primary
      cells.
AB  - Eradication of HIV infection depends on the elimination of a small, but stable
      population of latently infected T cells. After the discontinuation of therapy,
      activation of latent virus can rekindle infection. To purge this reservoir, it is
      necessary to define cellular signaling pathways that lead to activation of latent
      HIV. We used the SCID-hu (Thy/Liv) mouse model of HIV latency to analyze a broad
      array of T cell-signaling pathways and show in primary, quiescent cells that
      viral induction depends on the activation of two primary intracellular signaling
      pathways, protein kinase C or nuclear factor of activated T cells (NF-AT). In
      contrast, inhibition or activation of other important T cell stimulatory pathways
      (such as mitogen-activated protein kinase, calcium flux, or histone
      deacetylation) do not significantly induce virus expression. We found that the
      activation of NF-kappaB is critical to viral reactivation; however, all pathways
      that stimulate NF-kappaBdonot reactivate latent virus. Our studies further show
      that inhibition of NF-kappaB does not prevent activation of HIV by NF-AT,
      indicating that these pathways can function independently to activate the HIV
      LTR. Thus, we define several molecular pathways that trigger HIV reactivation
      from latency and provide evidence that latent HIV infection is maintained by the
      functional lack of particular transcription factors in quiescent cells.

PMID- 14569009
TI  - Induction of crossreactive antibodies against the Plasmodium falciparum variant
      protein.
AB  - The variant antigen Plasmodium falciparum erythrocyte membrane protein 1
      (PfEMP1), present on the surface of P. falciparum-parasitized erythrocytes (PE),
      plays a central role in naturally acquired immunity, although antibodies to
      PfEMP1 are predominantly variant specific. To overcome this major limitation for
      vaccine development, we immunized mice with three cysteine-rich interdomain 1
      (CIDR1) domains of PfEMP1 that have the critical function of binding the PE to
      CD36 on endothelium and thus preventing spleen-dependent killing of the parasite.
      The immunizations consisted of different combinations of three CIDR1 encoded by
      DNA followed by recombinant protein boost. Immunizations with a single variant in
      a prime-boost regimen induced no or low cross-reactivity toward heterologous
      CIDR1; however, a broad range of crossreactivity was detected in mice that were
      immunized with all three variants simultaneously. The induced crossreactivity
      suggests that an anti-PfEMP1 vaccine may be possible.

PMID- 14569010
TI  - Elevated mutagenesis and decreased DNA repair at a transgene are associated with
      proliferation but not apoptosis in p53-deficient cells.
AB  - p53, the most commonly mutated gene in human tumors, is believed to play a
      crucial role in the prevention of cancer by protecting cells from mutation, a
      theory commonly known as the "Guardian of the Genome" hypothesis. There are two
      hypotheses as to how this can occur. In the first, p53 protects the genome by
      retarding the cell cycle, thus allowing more time for DNA repair. In the second,
      p53 reduces cancer by initiating apoptosis in damaged cells, thus making it
      impossible for these cells to become carcinogenic. This study directly tested
      these two theories in primary murine embryonic fibroblasts on a common genetic
      background with and without p53, using a lacI transgene as a mutational target.
      The data demonstrate that, as a direct consequence of cell cycle delay, p53
      slowed the induction of mutations and decreased their frequency but had little
      effect on the frequency of apoptosis. This indicates that the function of p53 in
      cell cycle control is more important than the role of p53 in apoptosis, for
      mutation prevention, in any uniform cell population. Moreover, p53-mediated
      protection is further improved in slowly dividing cells, suggesting that p53 may
      be particularly important in protecting stem cells from mutation. The role of
      apoptosis in vivo, however, may be to remove whole tissue subpopulations that can
      be renewed by less sensitive stem cells.

PMID- 14569012
TI  - Detecting elusive surface atoms with atomic force microscopy.

PMID- 14569011
TI  - Conformational changes in the C terminus of Shaker K+ channel bound to the rat
      Kvbeta2-subunit.
AB  - We studied the structure of the C terminus of the Shaker potassium channel. The
      3D structures of the full-length and a C-terminal deletion (Delta C) mutant of
      Shaker were determined by electron microscopy and single-particle analysis. The
      difference map between the full-length and the truncated channels clearly shows a
      compact density, located on the sides of the T1 domain, that corresponds to a
      large part of the C terminus. We also expressed and purified both WT and Delta C
      Shaker, assembled with the rat KvBeta2-subunit. By using a difference map between
      the full-length and truncated Shaker alpha-beta complexes, a conformational
      change was identified that shifts a large part of the C terminus away from the
      membrane domain and into close contact with the Beta-subunit. This conformational
      change, induced by the binding of the KvBeta2-subunit, suggests a possible
      mechanism for the modulation of the K+ voltage-gated channel function by its Beta
      subunit.

PMID- 14569013
TI  - The energetics of structural change in maltose-binding protein.

PMID- 14569014
TI  - Convergent evolution of bright coloration and toxicity in frogs.

PMID- 14569015
TI  - Using nonequilibrium measurements to determine macromolecule free-energy
      differences.

PMID- 14569016
TI  - The single capillary and the active brain.

PMID- 14569017
TI  - Beta-adrenergic regulation requires direct anchoring of PKA to cardiac CaV1.2
      channels via a leucine zipper interaction with A kinase-anchoring protein 15.
AB  - Activation of beta-adrenergic receptors and consequent phosphorylation by cAMP
      dependent protein kinase A (PKA) greatly increases the L-type Ca2+ current
      through CaV1.2 channels in isolated cardiac myocytes. A kinase-anchoring protein
      15 (AKAP15) coimmunoprecipitates with CaV1.2 channels isolated from rat heart
      membrane extracts and transfected cells, and it colocalizes with CaV1.2 channels
      and PKA in the transverse tubules of isolated ventricular myocytes. Site-directed
      mutagenesis studies reveal that AKAP15 directly interacts with the distal C
      terminus of the cardiac CaV1.2 channel via a leucine zipper-like motif.
      Disruption of PKA anchoring to CaV1.2 channels via AKAP15 using competing
      peptides markedly inhibits the beta-adrenergic regulation of CaV1.2 channels via
      the PKA pathway in ventricular myocytes. These results identify a conserved
      leucine zipper motif in the C terminus of the CaV1 family of Ca2+ channels that
      directly anchors an AKAP15-PKA signaling complex to ensure rapid and efficient
      regulation of L-type Ca2+ currents in response to beta-adrenergic stimulation and
      local increases in cAMP.

PMID- 14569018
TI  - Expression of T cell receptor beta locus in central nervous system neurons.
AB  - MHC class I proteins are cell-surface ligands that bind to T cell receptors and
      other immunoreceptors and act to regulate the activation state of immune cells.
      Recent work has shown that MHC class I genes and CD3zeta, an obligate component
      of T cell receptors, are expressed in neurons, are regulated by neuronal
      activity, and function in neuronal development and plasticity. A search for
      additional neuronally expressed T cell receptor components has revealed that the
      T cell antigen receptor beta (TCRbeta) locus is expressed in neurons of the
      murine central nervous system and that this expression is dynamically regulated
      over development. In neonates, expression is most abundant in various thalamic
      nuclei. At later ages and in adults, thalamic expression fades and cortical
      expression is robust, particularly in layer 6. In T cells, protein-encoding
      transcripts are produced only after recombination of the TCRbeta genomic locus,
      which joins variable, diversity, and joining regions, a process that creates much
      of the diversity of the immune system. We detect no genomic recombination in
      neurons. Rather, transcripts begin in regions upstream of several joining
      regions, and are spliced to constant region segments. One of the transcripts
      encodes a hypothetical 207-aa, 23-kDa protein, which includes the TCRbeta J2.7
      region, and the entire C region. These observations suggest that TCRbeta may
      function in neurons.

PMID- 14569019
TI  - Fast protein folding kinetics.
AB  - Proteins are complex molecules, yet their folding kinetics is often fast
      (microseconds) and simple, involving only a single exponential function of time
      (called two-state kinetics). The main model for two-state kinetics has been
      transition-state theory, where an energy barrier defines a slow step to reach an
      improbable structure. But how can barriers explain fast processes, such as
      folding? We study a simple model with rigorous kinetics that explains the high
      speed instead as a result of the microscopic parallelization of folding
      trajectories. The single exponential results from a separation of timescales; the
      parallelization of routes is high at the start of folding and low thereafter. The
      ensemble of rate-limiting chain conformations is different from in transition
      state theory; it is broad, overlaps with the denatured state, is not aligned
      along a single reaction coordinate, and involves well populated, rather than
      improbable, structures.

PMID- 14569020
TI  - The Nagata automorphism is wild.
AB  - It is proved that the well known Nagata automorphism of the polynomial ring in
      three variables over a field of characteristic zero is wild, that is, it can not
      be decomposed into a product of elementary automorphisms.

PMID- 14569021
TI  - Evidence that IgE molecules mediate a spectrum of effects on mast cell survival
      and activation via aggregation of the FcepsilonRI.
AB  - We demonstrate that binding of different IgE molecules (IgEs) to their receptor,
      FcepsilonRI, induces a spectrum of activation events in the absence of a specific
      antigen and provide evidence that such activation reflects aggregation of
      FcepsilonRI. Highly cytokinergic IgEs can efficiently induce production of
      cytokines and render mast cells resistant to apoptosis in an autocrine fashion,
      whereas poorly cytokinergic IgEs induce these effects inefficiently. Highly
      cytokinergic IgEs seem to induce more extensive FcepsilonRI aggregation than do
      poorly cytokinergic IgEs, which leads to stronger mast cell activation and
      survival effects. These effects of both types of IgEs require Syk tyrosine kinase
      and can be inhibited by FcepsilonRI disaggregation with monovalent hapten. In
      hybridoma-transplanted mice, mucosal mast cell numbers correlate with serum IgE
      levels. Therefore, survival effects of IgE could contribute to the pathogenesis
      of allergic disease.

PMID- 14569022
TI  - Signature quantization.
AB  - We associate to the action of a compact Lie group G on a line bundle over a
      compact oriented even-dimensional manifold a virtual representation of G using a
      twisted version of the signature operator. We obtain analogues of various
      theorems in the more standard theory of geometric quantization.

PMID- 14569023
TI  - Reverse genetics with a full-length infectious cDNA of severe acute respiratory
      syndrome coronavirus.
AB  - A previously undescribed coronavirus (CoV) is the etiologic agent responsible for
      severe acute respiratory syndrome (SARS). Using a panel of contiguous cDNAs that
      span the entire genome, we have assembled a full-length cDNA of the SARS-CoV
      Urbani strain, and have rescued molecularly cloned SARS viruses (infectious clone
      SARS-CoV) that contained the expected marker mutations inserted into the
      component clones. Recombinant viruses replicated as efficiently as WT virus and
      both were inhibited by treatment with the cysteine proteinase inhibitor (2S,3S)
      transepoxysuccinyl-L-leucylamido-3-methylbutane ethyl ester. In addition,
      subgenomic transcripts were initiated from the consensus sequence ACGAAC in both
      the WT and infectious clone SARS-CoV. Availability of a SARS-CoV full-length cDNA
      provides a template for manipulation of the viral genome, allowing for the rapid
      and rational development and testing of candidate vaccines and therapeutics
      against this important human pathogen.

PMID- 14569024
TI  - The Tat/TAR-dependent phosphorylation of RNA polymerase II C-terminal domain
      stimulates cotranscriptional capping of HIV-1 mRNA.
AB  - The HIV type 1 (HIV-1) Tat protein stimulates transcription elongation by
      recruiting P-TEFb (CDK9/cyclin T1) to the transactivation response (TAR) RNA
      structure. Tat-induced CDK9 kinase has been shown to phosphorylate Ser-5 of RNA
      polymerase II (RNAP II) C-terminal domain (CTD). Results presented here
      demonstrate that Tat-induced Ser-5 phosphorylation of CTD by P-TEFb stimulates
      the guanylyltransferase activity of human capping enzyme and RNA cap formation.
      Sequential phosphorylation of CTD by Tat-induced P-TEFb enhances the stimulation
      of human capping enzyme guanylyltransferase activity and RNA cap formation by
      transcription factor IIH-mediated CTD phosphorylation. Using an immobilized
      template assay that permits isolation of transcription complexes, we show that
      Tat/TAR-dependent phosphorylation of RNAP II CTD stimulates cotranscriptional
      capping of HIV-1 mRNA. Upon transcriptional induction of latently infected cells,
      accumulation of capped transcripts occurs along with Ser-5-phosphorylated RNAP II
      in the promoter proximal region of the HIV-1 genome. Therefore, these
      observations suggest that Tat/TAR-dependent phosphorylation of RNAP II CTD is
      crucial not only in promoting transcription elongation but also in stimulating
      nascent viral RNA capping.

PMID- 14569026
TI  - Mixotrophs combine resource use to outcompete specialists: implications for
      aquatic food webs.
AB  - The majority of organisms can be grouped into those relying solely on
      photosynthesis (phototrophy) or those relying solely on the assimilation of
      organic substances (heterotrophy) to meet their requirements for energy and
      carbon. However, a special life history trait exists in which organisms combine
      both phototrophy and heterotrophy. Such "mixotrophy" is a widespread phenomenon
      in aquatic habitats and is observed in many protozoan and metazoan organisms. The
      strategy requires investment in both photosynthetic and heterotrophic cellular
      apparatus, and the benefits must outweigh these costs. In accordance with
      mechanistic resource competition theory, laboratory experiments revealed that
      pigmented mixotrophs combined light, mineral nutrients, and prey as substitutable
      resources. Thereby, they reduced prey abundance below the critical food
      concentration of competing specialist grazers [Rothhaupt, K. O. (1996) Ecology
      77, 716-724]. Here, we demonstrate the important consequences of this strategy
      for an aquatic community. In the illuminated surface strata of a lake, mixotrophs
      reduced prey abundance steeply. The data suggest that, as a consequence, grazers
      from higher trophic levels, consuming both the mixotrophs and their prey, could
      not persist. Thus, the mixotrophs escaped from competition with and losses to
      higher grazers. Furthermore, the mixotrophs structured prey abundance along the
      vertical light gradient, creating low densities near the surface and a pronounced
      maximum of their algal prey at depth. Such deep algal accumulations are typical
      features of nutrient-poor aquatic habitats, previously explained by resource
      availability. We hypothesize instead that the mixotrophic grazing strategy is
      responsible for deep algal accumulations in many aquatic environments.

PMID- 14569025
TI  - Twin concordance and sibling recurrence rates in multiple sclerosis.
AB  - Size and ascertainment constraints often limit twin studies to concordance
      comparisons between identical and fraternal twins. Here we report the final
      results of a longitudinal, population-based study of twins with multiple
      sclerosis (MS) in Canada. Bias was demonstrably minimized, and an estimated 75%
      of all Canadian MS twin pairs were ascertained, giving a sample sufficiently
      large (n = 370) to permit additional informative comparisons. Twinning was not
      found to affect prevalence, and twins with MS did not differ from nontwins for
      DR15 allele frequency nor for MS risk to their siblings. Probandwise concordance
      rates of 25.3% (SE +/- 4.4) for monozygotic (MZ), 5.4% (+/-2.8) for dizygotic
      (DZ), and 2.9% (+/-0.6) for their nontwin siblings were found. MZ twin
      concordance was in excess of DZ twin concordance. The excess concordance in MZ
      was derived primarily from like-sexed female pairs with a probandwise concordance
      rate of 34 of 100 (34 +/- 5.7%) compared with 3 of 79 (3.8 +/- 2.8%) for female
      DZ pairs. We did not demonstrate an MZ/DZ difference in males, although the
      sample size was small. We observed a 2-fold increase in risk to DZ twins over
      nontwin siblings of twins, but the difference was not significant.

PMID- 14569027
TI  - The complexity of alternative splicing of hagoromo mRNAs is increased in an
      explosively speciated lineage in East African cichlids.
AB  - The adaptive radiation of cichlid fishes in the lakes of East Africa is a prime
      example of speciation. The choice of cichlid mates on the basis of a variety of
      coloration represents a potential basis for speciation that led to adaptive
      radiation. Here, we characterize the cichlid homolog of the zebrafish hagoromo
      (hag) gene that was recently cloned and characterized from a pigmentation mutant.
      Although only one hag mRNA was reported in zebrafish, cichlids express nine
      different hag mRNAs resulting from alternative splicing. The hag mRNAs are
      expressed between the myotome and the epidermis where pigment cells are located,
      suggesting the cichlid hag gene is involved in pigmentation. The hag mRNA
      splicing pattern does not fluctuate among individuals from each of two species,
      suggesting that alternative splice site choice is fixed within species.
      Furthermore, cichlids in lineages that underwent explosive speciation expressed a
      greater variety of hag mRNAs than those in lineages that did not undergo such a
      degree of speciation, suggesting that species in the explosively speciated
      lineage acquired a complex regulatory mechanism of alternative splicing over a
      very short evolutionary period. Here, we provide an example in which alternative
      splicing may play a role in mate choice, leading to cichlid speciation through
      diversification of gene function by production of multiple mRNAs from a single
      gene.

PMID- 14569028
TI  - Conformation-dependent hydrophobic photolabeling of the nicotinic receptor:
      electrophysiology-coordinated photochemistry and mass spectrometry.
AB  - We characterized the differential accessibility of the nicotinic acetylcholine
      receptor alpha1 subunit in the open, closed, and desensitized states by using
      electrophysiology-coordinated photolabeling by several lipophilic probes followed
      by mass spectrometric analysis. Voltage-clamped oocytes expressing receptors were
      preincubated with one of the lipophilic probes and were continually exposed to
      acetylcholine; UV irradiation was applied during 500-ms pulses to + 40 or to -140
      mV (which produced closed or approximately 50% open receptors, respectively). In
      the open state, there was specific probe incorporation within the N-terminal
      domain at residues that align with the beta8-beta9 loop of the acetylcholine
      binding protein. In the closed state, probe incorporation was identified at
      several sites of the N-terminal domain within the conserved cysteine loop
      (residues 128-142), the cytoplasmic loop (M3-M4), and M4. The labeling pattern in
      the M4 region is consistent with previous results, further defining the lipid
      exposed face of this transmembrane alpha-helix. These results show regions within
      the N-terminal domain that are involved in gating-dependent conformational
      shifts, confirm that the cysteine loop resides at or near the protein-membrane
      interface, and show that segments of the M3-M4 loop are near to the lipid
      bilayer.

PMID- 14569029
TI  - Two-photon imaging of capillary blood flow in olfactory bulb glomeruli.
AB  - Analysis of the spatiotemporal coupling between neuronal activity and cerebral
      blood flow requires the precise measurement of the dynamics of RBC flow in
      individual capillaries that irrigate activated neurons. Here, we use two-photon
      microscopy in vivo to image individual RBCs in glomerular capillaries in the rat
      dorsal olfactory bulb. We find that odor stimulation evokes capillary vascular
      responses that are odorant- and glomerulus-specific. These responses consist of
      increases as well as decreases in RBC flow, both resulting from independent
      changes in RBC velocity or linear density. Finally, measuring RBC flow with
      micrometer spatial resolution and millisecond temporal resolution, we demonstrate
      that, in olfactory bulb superficial layers, capillary vascular responses
      precisely outline regions of synaptic activation.

PMID- 14569030
TI  - Genetic requirements for mycobacterial survival during infection.
AB  - Despite the importance of tuberculosis as a public health problem, we know
      relatively little about the molecular mechanisms used by the causative organism,
      Mycobacterium tuberculosis, to persist in the host. To define these mechanisms,
      we have mutated virtually every nonessential gene of M. tuberculosis and
      determined the effect disrupting each gene on the growth rate of this pathogen
      during infection. A total of 194 genes that are specifically required for
      mycobacterial growth in vivo were identified. The behavior of these mutants
      provides a detailed view of the changing environment that the bacterium
      encounters as infection proceeds. A surprisingly large fraction of these genes
      are unique to mycobacteria and closely related species, indicating that many of
      the strategies used by this unusual group of organisms are fundamentally
      different from other pathogens

PMID- 14569033
TI  - Behavioral interventions for obesity: recognizing our progress and future
      challenges.

PMID- 14569031
TI  - Active sites of thioredoxin reductases: why selenoproteins?
AB  - Selenium, an essential trace element for mammals, is incorporated into a selected
      class of selenoproteins as selenocysteine. All known isoenzymes of mammalian
      thioredoxin (Trx) reductases (TrxRs) employ selenium in the C-terminal redox
      center -Gly-Cys-Sec-Gly-COOH for reduction of Trx and other substrates, whereas
      the corresponding sequence in Drosophila melanogaster TrxR is -Ser-Cys-Cys-Ser
      COOH. Surprisingly, the catalytic competence of these orthologous enzymes is
      similar, whereas direct Sec-to-Cys substitution of mammalian TrxR, or other
      selenoenzymes, yields almost inactive enzyme. TrxRs are therefore ideal for
      studying the biology of selenocysteine by comparative enzymology. Here we show
      that the serine residues flanking the C-terminal Cys residues of Drosophila TrxRs
      are responsible for activating the cysteines to match the catalytic efficiency of
      a selenocysteine-cysteine pair as in mammalian TrxR, obviating the need for
      selenium. This finding suggests that the occurrence of selenoenzymes, which
      implies that the organism is selenium-dependent, is not necessarily associated
      with improved enzyme efficiency. Our data suggest that the selective advantage of
      selenoenzymes is a broader range of substrates and a broader range of
      microenvironmental conditions in which enzyme activity is possible.

PMID- 14569034
TI  - Combating obesity: challenges and choices.

PMID- 14569035
TI  - The changing environment and population obesity in the United States.
AB  - The recent unexpected increases in the prevalence of obesity in the United States
      are widely agreed to be the result of changes in environmental conditions. This
      paper reviews the available data from diverse sources on environmental factors
      and obesity. Coverage includes descriptive data on temporal trends in the
      environment, cross-sectional and longitudinal studies of the association between
      environmental exposures and body weight, and experimental trials that have
      related environmental factors thought to be potentially important in influencing
      energy intake and expenditure and body weight. Over the period covered by the
      "obesity epidemic," a variety of environmental factors have changed dramatically.
      Some would seem to favor increased body weight (e.g., increased availability of
      convenience foods and increased use of automobiles and televised entertainment),
      and others would seem to favor decreased body weight (e.g., a lower-fat food
      supply and the increased availability of some forms of physical activity).
      Definitive conclusions about the relative contributions of energy intake and
      expenditure to increasing body weight or about the contribution of specific
      environmental exposures to increasing body weight are far from clear. Increased
      sophistication in methods for making valid inferences from existing environmental
      data would be helpful. Even more important, given the urgency of the problem, is
      experimental research on the question of what environmental changes would be
      necessary to reverse the obesity epidemic.

PMID- 14569036
TI  - Are current health behavioral change models helpful in guiding prevention of
      weight gain efforts?
AB  - Effective procedures are needed to prevent the substantial increases in adiposity
      that have been occurring among children and adults. Behavioral change may occur
      as a result of changes in variables that mediate interventions. These mediating
      variables have typically come from the theories or models used to understand
      behavior. Seven categories of theories and models are reviewed to define the
      concepts and to identify the motivational mechanism(s), the resources that a
      person needs for change, the processes by which behavioral change is likely to
      occur, and the procedures necessary to promote change. Although each model has
      something to offer obesity prevention, the early promise can be achieved only
      with substantial additional research in which these models are applied to diet
      and physical activity in regard to obesity. The most promising avenues for such
      research seem to be using the latest variants of the Theory of Planned Behavior
      and Social Ecology. Synergy may be achieved by taking the most promising concepts
      from each model and integrating them for use with specific populations. Biology
      based steps in an eating or physical activity event are identified, and research
      issues are suggested to integrate behavioral and biological approaches to
      understanding eating and physical activity behaviors. Social marketing procedures
      have much to offer in terms of organizing and strategizing behavioral change
      programs to incorporate these theoretical ideas. More research is needed to
      assess the true potential for these models to contribute to our understanding of
      obesity-related diet and physical activity practices, and in turn, to obesity
      prevention.

PMID- 14569037
TI  - Self-regulation of energy intake in the prevention and treatment of obesity: is
      it feasible?
AB  - The prevalence of obesity in developed countries has been steadily increasing.
      Comprehensive lifestyle change programs for the treatment of obesity have
      garnered considerable empirical support, but most weight lost in lifestyle
      interventions is regained within several years. The outcome of obesity prevention
      programs has also been disappointing. One reason for this state of affairs may be
      that most weight control programs are based on an assumption of equipotentiality
      of their intervention components. That is, obesity prevention and treatment
      programs consist of a multitude of behavioral, cognitive, nutritional, physical
      activity, and interpersonal techniques, all of which are assumed to be of roughly
      equal importance in weight control. However, there is considerable evidence that
      our evolutionary heritage has made most humans highly sensitive to the
      availability and nature of food in the environment. It therefore may be
      unrealistic to expect that enhancing self-regulatory skills will be sufficient to
      overcome the combined influence of our appetitive predispositions and the
      obesigenic environment. However, there is growing evidence that weight control
      interventions that focus on the availability, structure, composition, and portion
      size of foods in the diet improve long-term weight control. Concerted efforts to
      change the availability and nature of foods at both the individual and population
      level may hold considerable promise for the treatment and prevention of obesity.

PMID- 14569038
TI  - An objective method for measurement of sedentary behavior in 3- to 4-year olds.
AB  - OBJECTIVE: To test the ability of accelerometry to quantify sedentary behavior in
      3- to 4-year-old children. RESEARCH METHODS AND PROCEDURES: We developed a cut
      off for accelerometry output (validation study) in 30 healthy 3 to 4 year olds,
      which provided highest sensitivity and specificity for the detection of sedentary
      behavior relative to a criterion method of measurement, direct observation using
      the children's physical activity form. We then cross-validated the cut-off in an
      independent sample of healthy 3 to 4 year olds (n = 52). RESULTS: In the
      validation study, optimal sensitivity and specificity for the detection of
      sedentary behavior were obtained at an accelerometry output cut-off of <1100
      counts/min. In the cross-validation, sensitivity was 83%: 438/528 inactive
      minutes were correctly classified. Specificity was 82%: 1251/1526 noninactive
      minutes were correctly classified using this cut-off. DISCUSSION: Sedentary
      behavior can be quantified objectively in young children using accelerometry.
      This new technique could be considered for a wide variety of applications in the
      etiology, prevention, and treatment of childhood obesity.

PMID- 14569039
TI  - Relationship between body weight gain and significant knee, hip, and back pain in
      older Americans.
AB  - OBJECTIVE: To examine the association between BMI (kilograms per meter squared)
      and reports of significant knee, hip, and back pain using data from a nationally
      representative sample of U.S. adults 60 years or older. RESEARCH METHODS AND
      PROCEDURES: Population-based survey data from the Third National Health and
      Nutrition Examination Survey, involving 5724 adults 60 years or older, were used.
      BMI, calculated from measured weight (kilograms) and height (meters squared), was
      used to categorize participants into six BMI-defined groups: underweight (<18.5),
      desirable weight (18.5 to 24.9), overweight (25 to 29.9), obese class I (30 to
      34.9), obese class II (35 to 39.9), and obese class III (>/=40). The presence of
      significant knee, hip, and back pain in the groups was studied. RESULTS: The
      overall prevalences of knee, hip, and back pain were 21%, 14%, and 22%,
      respectively. Prevalence estimates for knee (underweight 12.1% to obesity class
      III 55.7%), hip (underweight 10.4% to obesity class III 23.3%), and back
      (underweight 20.2% to obesity class III 26.1%) pain increased with increased BMI.
      Sex-, race-, and age-specific pain prevalence estimates also generally increased
      at increased levels of BMI. DISCUSSION: Among U.S. adults 60 years or older, the
      prevalence of significant knee, hip, and back pain increases with increased
      levels of BMI.

PMID- 14569040
TI  - Role of the DGAT gene C79T single-nucleotide polymorphism in French obese
      subjects.
AB  - Acyl-coenzyme A, diacylglycerol acyltransferase (DGAT), is a key enzyme involved
      in adipose-cell triglyceride storage. A 79-bp T-to-C single-nucleotide
      polymorphism (SNP) on the 3' region of the DGAT transcriptional site has been
      reported to increase promoter activity and is associated with higher BMI in
      Turkish women. To validate the possible role of this genetic variant in obesity,
      as well as the variant's possible cellular-functional significance, we performed
      an association study between the T79C change and several obesity-related
      phenotypes in 1357 obese French adults and children. The prevalence of the T79C
      SNP was similar between obese adults and children when each group was compared
      with the controls. (CC genotype carrier frequencies were 0.25 to 0.29 in the
      obese groups and 0.21 in controls; p > 0.05.) In each of the obese adult and
      child groups studied, the T79C variant was not found to be associated with any of
      the obesity-related phenotypes tested. Although the T79C SNP of the DGAT gene was
      studied in several groups of white subjects, the association between this SNP and
      obesity-related phenotypes, previously described, was not confirmed in our
      population.

PMID- 14569041
TI  - Primary care physicians' attitudes about obesity and its treatment.
AB  - OBJECTIVE: This study was designed to assess physicians' attitudes toward obese
      patients and the causes and treatment of obesity. RESEARCH METHODS AND
      PROCEDURES: A questionnaire assessed attitudes in 2 geographically representative
      national random samples of 5000 primary care physicians. In one sample (N =
      2500), obesity was defined as a BMI of 30 to 40 kg/m(2), and in the other (N =
      2500), obesity was defined as a BMI > 40. RESULTS: Six hundred twenty physicians
      responded. They rated physical inactivity as significantly more important than
      any other cause of obesity (p < 0.0009). Two other behavioral factors-overeating
      and a high-fat diet-received the next highest mean ratings. More than 50% of
      physicians viewed obese patients as awkward, unattractive, ugly, and
      noncompliant. The treatment of obesity was rated as significantly less effective
      (p < 0.001) than therapies for 9 of 10 chronic conditions. Most respondents
      (75%), however, agreed with the consensus recommendations that a 10% reduction in
      weight is sufficient to improve obesity-related health complications and viewed a
      14% weight loss (i.e., 78 +/- 5 kg from an initial weight of 91 kg) as an
      acceptable treatment outcome. More than one-half (54%) would spend more time
      working on weight management issues if their time was reimbursed appropriately.
      DISCUSSION: Primary care physicians view obesity as largely a behavioral problem
      and share our broader society's negative stereotypes about the personal
      attributes of obese persons. Practitioners are realistic about treatment outcomes
      but view obesity treatment as less effective than treatment of most other chronic
      conditions.

PMID- 14569042
TI  - Labor saved, calories lost: the energetic impact of domestic labor-saving
      devices.
AB  - OBJECTIVE: As the prevalence of obesity has increased, so has sedentariness.
      Progressive sedentariness has been attributed to greater use of labor saving
      devices, such as washing machines, and less nonexercise walking (e.g., walking to
      work). However, there is a paucity of data to support this conclusion. In this
      study, we address the hypothesis that domestic mechanization of daily tasks has
      resulted in less energy expenditure compared with performing the same tasks
      manually. RESEARCH METHODS AND PROCEDURES: Energy expenditure was measured in
      four groups of subjects (122 healthy adult men and women total) from Rochester,
      Minnesota. Energy expenditure was measured using indirect calorimetry while
      subjects performed structured tasks such as cleaning dishes and clothes, stair
      climbing, and work-associated transportation, and these values were compared with
      the respective mechanized activity. RESULTS: Energy expenditure was significantly
      greater and numerically substantial when daily domestic tasks were performed
      without the aid of machines or equipment (clothes washing: 45 +/- 14 vs. 27 +/- 9
      kcal/d; dish washing: 80 +/- 28 vs. 54 +/- 19 kcal/d; transportation to work: 83
      +/- 17 vs. 25 +/- 3 kcal/d; stair climbing: 11 +/- 7 vs. 3 +/- 1 kcal/d; p <
      0.05). The combined impact of domestic mechanization was substantial and equaled
      111 kcal/d. DISCUSSION: The magnitude of the energetic impact of the mechanized
      tasks we studied was sufficiently great to contribute to the positive energy
      balance associated with weight gain. Efforts focused on reversing sedentariness
      have the potential to impact obesity.

PMID- 14569043
TI  - Reduced expression of FOXC2 and brown adipogenic genes in human subjects with
      insulin resistance.
AB  - OBJECTIVE: We investigated subcutaneous adipose tissue expression of FOXC2 and
      selected genes involved in brown adipogenesis in adult human subjects in whom we
      have previously identified a reduced potential of precursor cell commitment to
      adipose-lineage differentiation in relation to insulin resistance. RESEARCH
      METHODS AND PROCEDURE: Gene expression was studied using quantitative real time
      polymerase chain reaction. The relation between the expression of brown
      adipogenic genes and the genes involved in progenitor cell commitment, adipose
      cell size, and insulin sensitivity in vivo was analyzed. RESULTS: The expression
      of FOXC2, MASK, MAP3K5, retinoblastoma protein (pRb), peroxisome proliferator
      activated protein gamma (PPARgamma), and retinoid X receptor gamma (RXRgamma) was
      decreased in the insulin-resistant compared with insulin-sensitive subjects,
      whereas PPARgamma-2 and CCAAT/enhancer binding protein alpha (C/EBPalpha) showed
      no differential expression. The FOXC2 expression correlated with that of Notch
      and Wnt signaling genes, as well as of the genes studied participating in brown
      adipogenesis, including MASK, MAP3K5, PPARgamma, pRb, RXRgamma, and PGC-1. A
      second-level correlation between PPARgamma and UCP-1 was also significant. In
      addition, the expression of MASK, MAP3K5, pRb, RXRgamma, and PGC-1 inversely
      correlated with adipose cell mass and also correlated with the glucose disposal
      rate in vivo. DISCUSSION: Our results suggest that a reduced brown adipose
      phenotype is associated with insulin resistance and that a basal brown adipose
      phenotype may be important for maintaining normal insulin sensitivity.

PMID- 14569044
TI  - Predicting total body fat from anthropometry in Latino children.
AB  - OBJECTIVE: To develop prediction equations for total body fat specific to Latino
      children, using demographic and anthropometric measures. RESEARCH METHODS AND
      PROCEDURES: Ninety-six Latino children (7 to 13 years old) were studied. Two
      thirds of the sample was randomized into the equation development group; the
      remainder served as the cross-validation group. Total body fat was measured by
      DXA. Measures included weight, height, waist and hip circumferences, and
      skinfolds (suprailiac, triceps, abdomen, subscapula, thigh, and calf). RESULTS:
      The previously published equation from Dezenberg et al. did not accurately
      predict total body fat in Latino children. However, newly developed equations
      with either body weight alone (intercept +/- SE = 1.78 +/- 1.53 kg, p > 0.05;
      slope +/- SE = 0.90 +/- 0.07, p > 0.05 against slope = 1.0; R(2) = 0.86), weight
      plus age and gender (intercept +/- SE = 2.28 +/- 1.20 kg, p > 0.05; slope +/- SE
      = 0.91 +/- 0.05, p > 0.05; against slope = 1.0; R(2) = 0.92), or weight plus
      height, gender, Tanner stage, and abdominal skinfold (intercept +/- SE = 1.47 +/-
      1.01 kg, p > 0.05; slope +/- SE = 0.93 +/- 0.04, p > 0.05; against slope = 1.0,
      R(2) = 0.97) predicted total body fat without bias. DISCUSSION: Unique prediction
      equations of total body fat may be needed for Latino children. Weight, as the
      single most significant predictor, can be used easily to estimate total body fat
      in the absence of any additional measures. Including age and gender with weight
      produces an equally stable prediction equation with increasing precision. Using a
      combination of demographic and anthropometric measures, we were able to capture
      97% of the variance in measured total body fat.

PMID- 14569045
TI  - Obesity and alcohol modulate the effect of apolipoprotein E polymorphism on
      lipids and insulin.
AB  - OBJECTIVE: To assess the interaction between apolipoprotein (apo) E polymorphism,
      alcohol consumption, and BMI on insulin, lipid, and lipoprotein levels in men.
      RESEARCH METHODS AND PROCEDURES: Cross-sectional study of 266 healthy men without
      hypolipidemic or antidiabetic drug treatment. BMI, apo E polymorphisms, insulin,
      and lipid and lipoprotein levels were assessed. Alcohol consumption was assessed
      by questionnaire. epsilon2/epsilon4 carriers were excluded from the analysis.
      RESULTS: On bivariate analysis, epsilon2 carriers had lower levels of total and
      low-density lipoprotein cholesterol and higher levels of apo E and lipoparticle
      B:E than epsilon3 carriers, the opposite being found for epsilon4 carriers
      compared with epsilon3 carriers; epsilon4 carriers also had significantly higher
      insulin levels. On multivariate analysis, significant interactions (p < 0.04)
      between apo E alleles and increased BMI were found for total and low-density
      lipoprotein cholesterol and insulin levels, the increase in those parameters with
      BMI being stronger among epsilon4 carriers than among epsilon3 or epsilon2
      carriers. Significant interactions (p < 0.02) between apo E alleles and alcohol
      consumption were also found for apo B levels, which increased in epsilon2
      carriers but remained relatively stable in epsilon3 and tended to decrease in
      epsilon4 carriers. DISCUSSION: These data suggest that effects of apo E alleles
      on lipids and insulin levels are partly dependent on environmental variables such
      as BMI and alcohol intake. These findings highlight the importance of gene x
      environment interactions on the deleterious effect of obesity on cardiovascular
      risk factors.

PMID- 14569046
TI  - Impact of weight loss and regain on quality of life: mirror image or differential
      effect?
AB  - OBJECTIVE: To compare the impact of weight regain and weight loss on health
      related quality of life. RESEARCH METHODS AND PROCEDURES: Subjects were 122 (106
      women, 16 men) overweight and obese participants in a weight reduction program
      (phentermine-fenfluramine and dietary counseling) who had initially lost at least
      5% of their total body weight and then regained at least 5% of their weight
      during the follow-up period. Follow-up periods ranged from 10 to 41 months (mean,
      28 months). Participants completed the Impact of Weight on Quality of Life-Lite,
      an obesity-specific health-related quality of life (HRQOL) measure, at 3-month
      intervals. RESULTS: Mean BMI at baseline was 40.9 +/- 6.6 kg/m(2) (range, 29.2 to
      63.7 kg/m(2)). Average weight loss from entry was 18.8 +/- 6.7% (range, 6.0% to
      43.7%), and average regain was 10.1 +/-4.4% of baseline weight (range, 5.0% to
      30.6%). The effects of weight regain on HRQOL mirrored the effects of weight loss
      rates of HRQOL change were similar in magnitude but different in direction for
      comparable weight loss and regain. Those with more severe initial impairments in
      HRQOL experienced greater improvements in HRQOL during weight loss as well as
      greater deterioration during weight regain than those with less severe
      impairments. DISCUSSION: Weight loss and regain produced mirror image changes in
      HRQOL. The initial severity of HRQOL impairment had a greater impact on the
      magnitude of HRQOL change than the direction of weight change. Findings
      underscore the importance of maintaining weight loss for the purposes of
      retaining obesity-specific HRQOL benefits.

PMID- 14569047
TI  - Adult female rats defend "appropriate" energy intake after adaptation to dietary
      energy.
AB  - OBJECTIVE: To determine if adult female rats adapt to lower and higher dietary
      energy density. RESEARCH METHODS AND PROCEDURES: Study 1 compared high-fat (56%),
      high-energy density (HD) (21.6 kJ/g) and high-fat (56%), low-energy density (LD)
      (16.0 kJ/g) diets before surgery (two groups, 2 weeks, n = 16) and after surgery
      [ovariectomy (O) Sham (S); 2 x 2 factorial, n = 8; 6 weeks]. The second study (no
      surgery) compared high-fat (60.0%), high-energy (22.0 kJ/g) and low-fat (10.0%),
      low-energy (15.1 kJ/g) diets (n = 8). RESULTS: In study 1, food intake was
      similar for the first 2 weeks, but rats on the LD diet consumed less energy,
      gained less weight, and had lower nonfasted serum leptin (all p < 0.0001) than
      rats on the HD diet. After surgery, rats on the LD and HD diets had similar
      weight gain, but rats on the LD diet consumed more food (p < 0.0001) and less
      energy (p < 0.009). O rats consumed more food and gained more weight (p < 0.0001)
      than S rats. Results from study 2 were similar to those from study 1. DISCUSSION:
      The results demonstrated that O and S surgery rats and rats with no surgery
      adjust their food intake to defend a level of energy intake. This defense only
      occurred after a 2-week adaptation period. The major differences in final body
      weights and abdominal fat resulted from the initial 2 weeks before adaptation to
      energy density. Rats fed higher-energy diets seemed to "settle" at a higher level
      of adiposity, and rats fed lower-energy diets consumed more food to increase
      energy consumption.

PMID- 14569048
TI  - Trends in waist circumference among U.S. adults.
AB  - OBJECTIVE: Waist circumference has been proposed as a measure of obesity or as an
      adjunct to other anthropometric measures to determine obesity. Our objective was
      to examine temporal trends in waist circumference among adults in the U.S.
      RESEARCH METHODS AND PROCEDURES: We used data from 15,454 participants >/=20
      years old in National Health and Nutrition Examination Survey (NHANES) III (1988
      to 1994) and 4024 participants >/=20 years old from National Health and Nutrition
      Examination Survey 1999 to 2000. RESULTS: The unadjusted waist circumference
      increased from 95.3 (age-adjusted, 96.0 cm) to 98.6 (age-adjusted, 98.9 cm) cm
      among men and from 88.7 (age-adjusted 88.9 cm) to 92.2 (age-adjusted 92.1 cm) cm
      among women. The percentiles from the two surveys suggest that much of the waist
      circumference distribution has shifted. Statistically significant increases
      occurred among all age groups and racial or ethnic groups except men 30 to 59
      years old, women 40 to 59 and >/=70 years old, and women who were Mexican
      American or of "other" race or ethnicity. DISCUSSION: These results demonstrate
      the rapid increase in obesity, especially abdominal obesity, among U.S. adults.
      Unless measures are taken to slow the increase in or reverse the course of the
      obesity epidemic, the burden of obesity-associated morbidity and mortality in the
      U.S. can be expected to increase substantially in future years.

PMID- 14569049
TI  - Effect of family history of type 2 diabetes on white blood cell count in adult
      women.
AB  - OBJECTIVE: To evaluate the effect of a first-degree family history of type 2
      diabetes on white blood cell (WBC) count, a risk factor for atherosclerotic
      vascular disease, in glucose-tolerant adult women. RESEARCH METHODS AND
      PROCEDURES: WBC count was measured in 174 normal weight, overweight, and obese
      female offspring of type 2 diabetic patients (FH(+)) and 174 age- and BMI-matched
      female controls with no family history of type 2 diabetes (FH(-)). Other
      measurements included fat mass (FM), measured by body impedance analysis; central
      fat accumulation, evaluated by waist circumference; insulin resistance, estimated
      by homeostatic model assessment for insulin resistance (HOMA(IR)); systolic and
      diastolic blood pressure; and fasting concentrations of glucose, insulin, and
      lipids. RESULTS: WBC count, waist circumference, systolic blood pressure, and
      fasting levels of glucose, insulin, and triglycerides were significantly higher
      in FH(+) than in FH(-) subjects. In FH(+) individuals, WBC count was positively
      associated with BMI, FM, waist circumference, HOMA(IR), and triglyceride and
      insulin concentrations, and negatively correlated with age and high-density
      lipoprotein-cholesterol. In FH(-) subjects, WBC count was directly associated
      with BMI, FM, waist circumference, and triglyceride and insulin concentrations,
      and inversely correlated with age and high-density lipoprotein-cholesterol. After
      multivariate analyses, WBC count maintained a significant association with age,
      systolic blood pressure, and HOMA(IR) in FH(+) subjects and with age, BMI, FM,
      and triglycerides in FH(-) individuals. DISCUSSION: This study indicates that WBC
      count is increased in adult women with genetic predisposition to type 2 diabetes,
      and its main correlates are insulin resistance in FH(+) and adiposity in FH(-)
      individuals.

PMID- 14569050
TI  - Intelligence test score and educational level in relation to BMI changes and
      obesity.
AB  - OBJECTIVE: To investigate whether intelligence and education are related to
      subsequent BMI changes and development and persistence of obesity in men from
      young adulthood through middle-age. RESEARCH METHODS AND PROCEDURES: Subjects
      were selected among men (median age, 19 years; examined between 1956 and 1977)
      appearing at Danish draft boards: a group with juvenile-onset obesity, including
      all men with a BMI of >/=31.0 kg/m(2); and a nonobese group randomly selected as
      a 1% sample of the study population. The obese group and 50% of the nonobese
      group were invited to participate in follow-up studies between 1982 and 1984 and
      between 1992 and 1994. Among 907 men with juvenile-onset obesity and 883 nonobese
      men, age, examination region, intelligence test score, education, and BMI from
      baseline to first follow-up were analyzed by multiple linear and logistic
      regressions analyses. RESULTS: Education and intelligence, analyzed separately,
      were inversely related to BMI changes in both groups and to the development of
      obesity in the nonobese group. When adjusted for education, the association
      between intelligence score and BMI changes and development of obesity vanished,
      whereas the inverse relationship for education persisted only for BMI changes.
      Intelligence score was not associated with the persistence of obesity in the
      obese group, whereas inverse relationships were found for education. DISCUSSION:
      Intelligence test score was inversely related to risk of BMI changes and the risk
      of development of obesity, perhaps with education acting as a mediator or
      indicator of cognitive ability. Education, but not intelligence, was inversely
      associated with risk of remaining obese.

PMID- 14569051
TI  - A festschrift for Roland L. Weinsier: nutrition scientist, educator, and
      clinician.
AB  - Roland L. Weinsier, M.D., Dr.P.H., devoted himself to the fields of nutrition and
      obesity for more than 35 years. He contributed outstanding work related to the
      treatment of obesity through dietary and lifestyle change; metabolic/energetic
      influences on obesity, weight loss, and weight regain; body composition changes
      accompanying weight loss and regain; the health benefits and risks of weight
      loss; nutrition education for physicians; and nutrition support of sick patients.
      He served on the National Institute of Diabetes and Digestive and Kidney Diseases
      (NIDDK) National Task Force on Prevention and Treatment of Obesity, as Chair of
      the University of Alabama at Birmingham's Department of Nutrition Sciences, and
      as Founder and Director of its NIDDK-funded Clinical Nutrition Research Center.
      He was a long-time and active member of NAASO, serving in the roles of Councilor,
      Publications Committee Chair, Continuing Medical Education Course Director,
      Public Relations Committee Chair, and Membership Committee Co-Chair, to name just
      a few. He was well respected as a staunch defender of NAASO's scientific
      integrity in these roles. Sadly, Roland Weinsier died on November 27, 2002. He
      will be missed and remembered by many as a revered and beloved teacher, mentor,
      healer, and scholar.

PMID- 14569052
TI  - Pathways to obesity prevention: report of a National Institutes of Health
      workshop.
AB  - There is an extensive research base on obesity treatment and on the health
      benefits of weight loss, but relatively little research has focused on obesity
      prevention. This article summarizes results of a workshop conducted by
      investigators funded under a National Institutes of Health initiative designed to
      stimulate novel research for obesity prevention. The 20 pilot studies funded
      under this initiative involved study populations that were diverse with respect
      to life stage and ethnicity, were conducted in a variety of natural and research
      settings, and involved a mix of interventions, including face-to-face group and
      individual counseling, as well as mail, telephone, and internet-based approaches.
      The workshop, which occurred approximately halfway through the 3-year funding
      period, emphasized concepts and experiences related to initiating and conducting
      obesity prevention studies. Investigators discussed theoretical perspectives as
      well as various challenges encountered, for example, in study implementation in
      different clinical and community settings, in working with children and families,
      and in studying pregnant and postpartum women. Other topics discussed included
      the difficulty of motivating individuals for prevention of weight gain, relevant
      cultural and racial/ethnic considerations, and the particular need for valid and
      practical measures of energy balance, body composition, and physical fitness in
      obesity prevention research. A key conclusion was that using obesity treatment as
      the primary paradigm may be a limiting perspective for considering obesity
      prevention issues. Further insights derived from the workshop deliberations are
      reflected in a detailed list of recommendations for future obesity prevention
      research.

PMID- 14569053
TI  - Effect of graded heart rate reduction with ivabradine on myocardial oxygen
      consumption and diastolic time in exercising dogs.
AB  - Lowering heart rate reduces myocardial oxygen consumption (MVO2) and produces
      potent anti-ischemic effects. The development of selective heart rate-reducing
      agents represents an alternative approach to the use of beta-blockers. Therefore,
      our goal was to establish the dose-response curve of the effects of ivabradine
      (If channel inhibitor) on MVO2 and diastolic time. Seven conscious and
      chronically instrumented dogs were investigated during exercise at spontaneous
      and paced heart rate (250 beats/min) after administration of increasing doses of
      ivabradine (0.25, 0.5, and 1 mg/kg i.v.). During exercise, ivabradine dose
      dependently and significantly reduced the exercise-induced tachycardia (-17, -21,
      and -32% at 0.25, 0.5, and 1 mg/kg, respectively, versus saline) without altering
      myocardial contractility nor mean ejection wall stress. A linear relationship
      between heart rate (HR) and MVO2 was demonstrated (MVO2 = 0.044 x HR - 1.4; r =
      0.987). These effects of ivabradine on MVO2 were abolished by atrial pacing.
      Similarly, ivabradine dose dependently increased diastolic time without altering
      the inverse and non linear relationship between diastolic time and heart rate
      observed with saline. In conclusion, selective heart rate reduction with
      ivabradine dose dependently increases diastolic time and reduces MVO2 with a
      linear relationship between heart rate and MVO2. The lack of "on-off"
      pharmacological profile will predict the possibility of using a wide range of
      dose regimen.

PMID- 14569054
TI  - A physiologically based approach for the estimation of recirculatory parameters.
AB  - Indicator dilution studies are used to provide estimates for several
      physiological parameters such as cardiac output as well as intra- and
      extravascular volumes. This study introduces a novel technique for the estimation
      of recirculatory parameters. A mathematical model based on a dispersion
      convection partial differential equation (PDE), derived from the fractal geometry
      of the vascular tree and the hydrodynamics of the blood flow, is used to describe
      the spatiotemporal profile of tracers in the circulatory system. Initially, the
      equation is fitted to concentration-time (C,t) data of a tracer to derive the
      parameter estimates of the model equation; in a subsequent step, these estimates
      along with appropriate changes of the parameters of the PDE are used to generate
      the early concentration-time profile of a hypothetical appropriate tracer without
      recirculation. Thus, the area under the concentration-time curve of the first
      passage of the tracer is calculated and used for the estimation of various
      physiological parameters, including cardiac output, miscellaneous partial blood
      volumes, and the corresponding mean transit times. The procedure was applied
      successfully to literature data of various tracers from humans and dogs.

PMID- 14569055
TI  - Cocaine and other indirect-acting monoamine agonists differentially attenuate a
      naltrexone discriminative stimulus in morphine-treated rhesus monkeys.
AB  - Monoaminergic drugs can modify opioid withdrawal in nonhumans, and cocaine is
      reported to attenuate opioid withdrawal in humans. Drug discrimination was used
      to examine whether s.c. cocaine or other indirect-acting monoamine agonists
      attenuate morphine (3.2 mg/kg/day) withdrawal induced by naltrexone and by 27 h
      of morphine deprivation. Naltrexone-precipitated withdrawal was attenuated not
      only by morphine but also by cocaine, amphetamine, and imipramine. However,
      reversal of naltrexone-precipitated withdrawal was greater for morphine than for
      any of the indirect-acting monoamine agonists. Attenuation of the naltrexone
      discriminative stimulus by indirect-acting monoamine agonists was
      pharmacologically selective insofar as drugs lacking affinity for monoamine
      transporters (ketamine and triazolam) were without effect. Twenty-seven hours of
      morphine deprivation occasioned naltrexone-lever responding and decreased
      response rate, and both effects were reversed by morphine, cocaine, and
      amphetamine and not by imipramine, desipramine, ketamine, and triazolam. Thus,
      indirect-acting monoamine agonists attenuate some (e.g., discriminative) aspects
      of naltrexone-precipitated withdrawal, whereas only indirect-acting agonists with
      high affinity for dopamine transporters attenuate deprivation-induced withdrawal.
      These results suggest that dopamine is differentially involved in naltrexone- and
      deprivation-induced withdrawal and support the notion that opioid-dependent
      individuals use stimulants, in part, to attenuate withdrawal.

PMID- 14569056
TI  - Effects of gamma-hydroxybutyrate (GHB) on schedule-controlled responding in rats:
      role of GHB and GABAB receptors.
AB  - Gamma-hydroxybutyrate (GHB), a metabolite of gamma-aminobutyric acid (GABA), is
      an increasingly popular drug of abuse and was recently approved for the treatment
      of narcolepsy (Xyrem). GHB and GABA receptors have been implicated in mediating
      effects of GHB; however, the relative importance of each of these receptors is
      unclear. This study evaluated the effects of selective antagonists in combination
      with GHB and related compounds on schedule-controlled responding. Eight male
      Sprague-Dawley rats responded under a fixed-ratio schedule of food presentation.
      Cumulative dose-effect curves were generated and ED50 values calculated to
      evaluate the relative potency at decreasing responding. The rank-order potency
      was as follows: diazepam = baclofen > gamma-butyrolactone (GBL) > 1,4-butanediol
      (1,4-BDL) = GHB. All compounds decreased responding 20 min after administration.
      The duration of action of diazepam, GHB, and GBL was shorter than that of 1,4-BDL
      and baclofen. p-3-Aminopropyl-p-diethoxymethyl phosphinic acid (CGP 35348)
      antagonized the rate-decreasing effects of baclofen and not GHB; flumazenil
      antagonized the effects of diazepam and not GHB. The GHB receptor antagonist (2E)
      (5-hydroxy-5,7,8,9-tetrahydro-6H-benzo[a][7]annulen-6-ylidene ethanoic acid (NCS
      382) did not attenuate the rate-decreasing effects of GHB, baclofen, or diazepam;
      larger doses of NCS-382 further decreased rate of responding when given in
      combination with each of these compounds. These studies show that GBL, 1,4-BDL,
      and GHB differ significantly in potency and duration of action. The ability of
      CGP 35348 to antagonize the rate-decreasing effects of baclofen may be limited by
      the involvement of multiple GABAB receptor subtypes and the lack of antagonism of
      GHB by NCS-382 may be due to its own GHB-like effects.

PMID- 14569057
TI  - Roles of catalase and hydrogen peroxide in green tea polyphenol-induced
      chemopreventive effects.
AB  - The green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) possesses
      promising anticancer potential. Although in vivo studies unveiled the metabolic
      routes and pharmacokinetics of EGCG and showed no adverse effects, in vitro
      studies at high concentrations demonstrated oxidative stress. EGCG causes
      differential oxidative environments in tumor versus normal epithelial cells, but
      the roles that EGCG, hydrogen peroxide (H2O2), and intracellular catalase play in
      the epithelial system are largely unknown. The current study employed enzyme
      activity assays, reactive oxygen species quantification, and immunoblotting to
      investigate whether EGCG-induced differential effects correlate with levels of
      key antioxidant enzymes and H2O2. It was found that normal human keratinocytes
      with high catalase activity are least susceptible to H2O2, whereas H2O2 caused
      significant cytotoxicity in oral carcinoma cell lines. However, the EGCG-induced
      differential effects could not be duplicated by H2O2 alone. The addition of
      exogenous catalase failed to completely prevent the EGCG-induced cytotoxicity and
      rescue the EGCG-induced growth arrest in the tumor cells. The antioxidant N
      acetyl-L-cysteine rescued the tumor cells from H2O2-induced damage only, but not
      from EGCG-induced mitochondrial damage. Finally, alterations in catalase or
      superoxide dismutase activities were not observed upon EGCG exposure. In
      conclusion, although endogenous catalase may play a role in response to H2O2
      induced cytotoxicity, the EGCG-induced cytotoxic effects on tumor cells mainly
      result from sources other than H2O2.

PMID- 14569058
TI  - Cilostazol enhances casein kinase 2 phosphorylation and suppresses tumor necrosis
      factor-alpha-induced increased phosphatase and tensin homolog deleted from
      chromosome 10 phosphorylation and apoptotic cell death in SK-N-SH cells.
AB  - This study shows the signaling pathway by which cilostazol suppresses tumor
      necrosis factor-alpha (TNF-alpha)-induced the phosphatase and tensin homolog
      deleted from chromosome 10 (PTEN) phosphorylation and apoptosis via casein kinase
      2 (CK2) phosphorylation in the SK-N-SH cells (neuroblastoma cells). Cilostazol
      (10 microM) fully restored cell proliferation with suppression of DNA
      fragmentation induced by TNF-alpha and emodin, a CK2 inhibitor, which were
      antagonized by iberiotoxin, a maxi-K channel blocker. Under application of TNF
      alpha or emodin, increased PTEN phosphorylation and decreased phosphorylation of
      CK2/Akt/cyclic AMP response element-binding protein (CREB), and CK2 activity were
      significantly reversed by cilostazol (approximately 1-100 microM), all of which
      were antagonized by iberiotoxin. 1,3-dihydro-1-[2-hydroxy-5
      (trifluoromethyl)phenyl]-5-(trifluoromethyl)-2H-benzimidazol-2-one (NS-1619) and
      (3S)-(+)-(5-chloro-2-methoxyphenyl-1,3-dihydro-3-fluoro-6-(trifluoromethyl)-2H
      indol-2-one (BMS 204352) maxi-K channel openers significantly elevated CK2
      activities that were reversible by iberiotoxin. SK-N-SH cells treated with
      antisense CK2 oligodeoxynucleotide showed a prominent DNA fragmentation with
      little responsiveness to TNF-alpha in the phosphorylation of PTEN, indicative of
      the essential role of p-CK2/CK2 in cell proliferation, and the decreased cell
      viability of these cells was not restored by cilostazol. It is suggested that the
      action of cilostazol promoting cell survival is ascribed to the maxi-K channel
      opening-coupled up-regulation of CK2 phosphorylation and down-regulation of PTEN
      phosphorylation with resultant increased phosphorylation of Akt and CREB.

PMID- 14569059
TI  - Oral treatment with recombinant human interleukin-11 improves mucosal transport
      in the colon of human leukocyte antigen-B27 transgenic rats.
AB  - Recombinant human interleukin (IL)-11 is a pleiotropic cytokine with anti
      inflammatory activity. The objective of the study was to investigate whether oral
      treatment with rhIL-11 improves colonic epithelial dysfunction in the human
      leukocyte antigen (HLA)-B27 transgenic rat model of spontaneous chronic
      inflammation. Experiments were performed using adult male HLAB27 rats, whereas
      healthy nontransgenic F344 rats served as controls. Enteric-coated rhIL-11 multi
      particles (equivalent to 500 microg/kg rhIL11) or placebo (formulation lacking
      rhIL-11) were administrated orally on alternate days for 2 weeks to HLA-B27 or
      F344 rats. Stool character was observed daily during the treatment period.
      Animals were euthanized at the end of treatment and colonic inflammation was
      evaluated be measuring tissue myeloperoxidase (MPO) activity. Epithelial
      transport in isolated colonic mucosal sheets was studied in modified Ussing
      chambers. Oral treatment of HLA-B27 rats with rhIL-11 reduced MPO activity in the
      colon and suppressed the clinical signs of diarrhea. The electrophysiological
      characteristics of mucosal transport were improved in the HLA-B27 rats treated
      with rhIL-11 compared with placebo. After rhIL-11 treatment the basal
      transepithelial resistance and the estimated paracellular resistance were
      significantly increased, neurally mediated secretory responses to electrical
      field stimulation were improved, and cholinoceptor sensitivity was normalized.
      Treatment with rhIL-11 had no significant effect on basal short circuit current
      and the maximal secretory response to carbachol or substance P. Our data
      demonstrate that oral rhIL-11 therapy is associated with suppression of mucosal
      inflammation and a concomitant improvement of epithelial resistance and neurally
      mediated secretion in a model of chronic HLA-B27 colitis.

PMID- 14569060
TI  - Role of receptor protein and membrane lipids in xanomeline wash-resistant binding
      to muscarinic M1 receptors.
AB  - Xanomeline is a novel agonist functionally selective for muscarinic receptors of
      the M1 subtype. It binds to this receptor in two modes, reversible and quasi
      irreversible (wash-resistant). We investigated the unknown mechanism of the wash
      resistant binding in experiments with muscarinic M1 receptors expressed in
      transfected Chinese hamster ovary cells. Xanomeline's structure consists of two
      heterocycles and O-hexyl side chain. We compared the wash-resistant binding of
      xanomeline and its analogs with shorter O-alkyl side chains. For the wash
      resistant binding to occur, the O-alkyl chain had to be at least O-butyl or
      longer. Accumulation of inositol phosphates was enhanced in washed cells that had
      been preexposed to xanomeline or its pentyl analog, whereas the agonistic effects
      of the methyl, propyl, and butyl analogs were abolished by washing. Only the
      reversible binding of xanomeline was detected purified soluble receptors, but
      both binding modes occurred purified receptors reconstituted into liposomes and
      exposed xanomeline only after reconstitution. The wash-resistant binding did not
      occur if the exposure of purified receptors or liposomes alone to xanomeline,
      followed by washing, reconstitution. Simultaneous presence of receptors and lipid
      environment is therefore essential for the binding to take place. We suggest that
      the binding of xanomeline involves interhelical penetration of M1 muscarinic
      receptor by xanomeline's O-alkyl chain and interaction with membrane lipids
      surrounding the receptor.

PMID- 14569061
TI  - Effects of 2-[N-(4-chlorophenyl)-N-methylamino]-4H-pyrido[3.2-e]-1,3-thiazin-4
      one (YM928), an orally active alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
      acid receptor antagonist, in models of generalized epileptic seizure in mice and
      rats.
AB  - The anticonvulsant activity of 2-[N-(4-chlorophenyl)-N-methylamino]-4H-pyrido[3.2
      e]-1,3-thiazin-4-one (YM928), a novel alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA) receptor antagonist, was studied in animal models
      of generalized seizure. YM928 exerted significant anticonvulsant effects in the
      maximal electroshock (MES) seizure test (ED50 = 7.4 mg/kg p.o.),
      pentylenetetrazol (PTZ)-induced seizure test (ED50 = 9.6 mg/kg p.o.), AMPA
      induced seizure test (ED50 = 5.5 mg/kg p.o.), and strychnine-induced seizure test
      (ED50 = 14.0 mg/kg p.o.) in mice. Effects in rats were detected in the MES
      seizure test (ED50 = 4.0 mg/kg p.o.) and PTZ-induced seizure test (ED50 = 6.2
      mg/kg p.o.). The profile of YM928 was compared with that of established
      antiepileptics. Valproate showed beneficial effects in all tests used. In
      contrast, carbamazepine, phenytoin, lamotrigine, phenobarbital, diazepam,
      ethosuximide, and gabapentin were not active against seizures induced by at least
      one stimulant. In the rotarod test, YM928 impaired motor coordination (TD50 =
      22.5 mg/kg p.o.). The protective index (TD50 value of the rotarod test/ED50 value
      of MES seizure) was 3.0, suggesting that YM928 can exert antiepileptic effects
      with only minor motor disturbances. YM928 at doses of 2, 4, and 8 mg/kg p.o. did
      not significantly affect the threshold of electroshock seizure in rats after 16
      days of repeated administration. These data indicate that YM928 does not induce
      tolerance after subchronic administration. These results indicate that YM928 is a
      broad-spectrum anticonvulsant that would prove useful for the treatment of
      generalized seizure in human epileptic patients.

PMID- 14569062
TI  - Nicotine promoted colon cancer growth via epidermal growth factor receptor, c
      Src, and 5-lipoxygenase-mediated signal pathway.
AB  - Nicotine [3-(1-methyl-2-pyrrolidinyl)-pyridine], a major alkaloid in tobacco, has
      been implicated as playing a role in carcinogenesis. Our previous study showed
      that passive cigarette smoking promoted inflammation-associated colonic adenoma
      formation in mice, and 5-lipoxygenase (5-LOX) plays an important role in this
      process. In the present study, we aimed to investigate whether nicotine could
      stimulate colon cancer cell proliferation and tumor growth in nude mice xenograft
      model and the possible mechanisms involved. Results showed that nicotine
      stimulated SW1116 colon cancer cell proliferation in a dose-dependent manner.
      Epidermal growth factor receptor (EGFR) and c-Src phosphorylation levels together
      with protein expression of 5-LOX were also significantly enhanced in this
      proliferation process. Inhibitors of EGFR and c-Src alleviated the actions of
      nicotine on cell proliferation and 5-LOX protein expression. Combination of both
      agents produced additive effect. In contrast, 5-LOX inhibitor had no direct
      effect on the phosphorylation levels of EGFR and c-Src and yet inhibited cell
      proliferation. In the colon cancer xenograft model, nicotine also significantly
      enhanced tumor growth. This acceleration of tumor growth corresponded well with
      increased vascularization and its proangiogenic factors. Inhibitors of EGFR, c
      Src, and 5-LOX all significantly impeded the tumor growth induced by nicotine.
      Together, nicotine can promote colonic tumorigenesis both in vitro and in vivo.
      Activation of the phosphorylated form of EGFR and c-Src followed by an increased
      5-LOX expression are the prime pathogenic mechanisms in the tumorigenic process
      in the colon.

PMID- 14569063
TI  - CYP3A4-transfected Caco-2 cells as a tool for understanding biochemical
      absorption barriers: studies with sirolimus and midazolam.
AB  - CYP3A4-transfected Caco-2 cells were used as an in vitro system to predict the
      importance of drug metabolism and transport on overall drug absorption. We
      examined the transport and metabolism of two drugs; midazolam, an anesthetic
      agent and CYP3A4 substrate, and sirolimus, an immunosuppressant and a dual
      CYP3A4/P-glycoprotein (P-gp) substrate, in the presence of cyclosporine (CsA, a
      CYP3A4/P-gp inhibitor) or N-[4-[2-(1,2,3,4-tetrahydro-6,7-dimethoxy-2
      isoquinolinyl)-ethyl]-phenyl]-9,10-dihydro-5-methoxy-9-oxo-4-acridine carboxamine
      (GG918) (an inhibitor of P-gp and not CYP3A4). All major CYP3A4 metabolites were
      formed in the cells (1-OH > 4-OH midazolam and 39-O-desmethyl > 12-OH > 11-OH
      sirolimus), consistent with results from human liver microsomes. There was no
      bidirectional transport of midazolam across CYP3A4-transfected Caco-2 cells,
      whereas there was a 2.5-fold net efflux of sirolimus (1 microM) that disappeared
      in the presence of CsA or GG918. No change in the absorption rate or extraction
      ratio (ER) for midazolam was observed when P-gp was inhibited with GG918.
      Addition of GG918 had a modest impact on the absorption rate and ER for sirolimus
      (increased 58% and decreased 25%, respectively), whereas a 6.1-fold increase in
      the absorption rate and a 75% decrease in the ER were found when sirolimus was
      combined with CsA. Although both midazolam and sirolimus metabolites were
      preferentially excreted to the apical compartment, only sirolimus metabolites
      were transported by P-gp as determined from inhibition studies with GG918. Using
      CYP3A4-transfected Caco-2 cells we determined that, in contrast to P-gp, CYP3A4
      is the major factor limiting sirolimus absorption. The integration of CYP3A4 and
      P-gp into a combined in vitro system was critical to unveil the relative
      importance of each biochemical barrier.

PMID- 14569064
TI  - Potent antioxidant properties of 4-hydroxyl-propranolol.
AB  - The antioxidant properties of 4-HO-propranolol (4HOP), a major metabolite of
      propranolol, were studied and compared with that of propranolol and vitamin E
      (Trolox). When isolated hepatic microsomal membranes were peroxidized by an iron
      catalyzed.OH-generating system [dihydroxyfumarate +Fe (III)], 4HOP potently and
      concentration-dependently inhibited lipid peroxidation; the IC50 value was 1.1
      microM, whereas those for Trolox and propranolol were 4.3 and 168 microM,
      respectively. When isolated human low-density lipoprotein (LDL) was oxidized by
      7.5 microM Cu(II) for 9 h, 4HOP at 3 microM delayed the lag phase significantly
      by 108 min, which was comparable with that of probucol (98-min delay) but was far
      greater than that provided by propranolol (6 min) or Trolox (47 min). At 1 microM
      4HOP, the delay was 45 min. When confluent cultured bovine aortic endothelial
      cells were exposed to the Fe-catalyzed oxy-radical system, acute loss of
      glutathione occurred (55% decrease in 50 min). Pretreatment of the cells with
      0.067 to 6.7 microM 4HOP for 30 min provided increasing degrees of protection
      against the glutathione loss; the EC50 value was 1.2 microM, whereas those for
      Trolox and propranolol were 7.9 and 49 microM, respectively. The loss of cell
      survival due to the radical stress was also effectively preserved by 4HOP. In
      separate experiments, when the endothelial glutathione was oxidatively depleted
      by a peroxynitrite-generating system (3-morpholinosydnonimine), 4HOP also
      provided potent protective activities. In conclusion, 4HOP is 4- to 8-fold more
      potent than vitamin E and >100-fold more active than propranolol as a "chain
      breaking" antiperoxidatant against membrane and LDL oxidation and can provide
      superior endothelial cytoprotective efficacy against oxygen- or nitrogen-derived
      oxidant-mediated cell injury. Being a major metabolite in human and with its
      plasma level approaching that of propranolol, 4-HO-propranolol may contribute, in
      part, to the cardiovascular therapeutic benefits of propranolol.

PMID- 14569065
TI  - Characterization of specific opioid binding sites in neural membranes from the
      myenteric plexus of porcine small intestine.
AB  - Delta- and kappa-opioid receptors (OPRs), but not micro-OPRs, are expressed in
      the myenteric plexus of the porcine distal small intestine. In a subpopulation of
      myenteric neurons, delta- and kappa-OPRs seem to be colocalized and may
      functionally interact. In this study, radioligand binding was used to
      characterize myenteric OPR populations in detail. The nonselective OPR antagonist
      [3H]diprenorphine bound to a single, high-affinity site in myenteric neural
      membrane homogenates. Naloxone displaced 65 and 59% of [3H]diprenorphine binding
      from this site in Na(+)-free Tris and Krebs-HEPES buffers, respectively.
      Naltrexone-derived delta- and kappa-OPR antagonists, including naltriben, 7
      benzylidenenaltrexone, nor-binaltorphimine, and 5'-guanidinonaltrindole,
      displaced [3H]diprenorphine from two distinct binding sites to levels similar to
      that of naloxone. The selective delta-OPR ligands Tyr-1,2,3,4
      tetrahydroisoquinoline-Phe-Phe-OH (TIPP), [D-Pen2,D-Pen5]enkephalin (DPDPE), [D
      Ala2, Glu4]deltorphin II, and (+)-4-[(alphaR)-alpha((2S,5R)-4-allyl-2,5-dimethyl
      1-piperazinyl-3-methoxybenzyl)-N,N-diethylbenzamide (SNC-80) and the kappa-OPR
      agonist (D-(5alpha,7alpha,8beta)-(-)-N-methyl-N-(7-(1-pyrrolidinyl)-1-oxoaspiro
      (4,5)dec-8-yl) benzeneacetamide (U-69,593) displaced [3H]diprenorphine from three
      independent binding sites; these included high-affinity delta- and kappa-OPR
      sites, and a residual binding site. Residual [3H]diprenorphine binding was
      displaced by the selective kappa-OPR antagonist nor-binaltorphimine after
      saturation of delta and kappa sites, respectively, with DPDPE and U-69,593. The
      residual binding site displayed low affinity for delta- and kappa-OPR agonists
      and TIPP, as well as moderate affinity for naltrexone-derived ligands, properties
      reminiscent of delta-/kappa-OPR heterodimers.

PMID- 14569067
TI  - Propafenone and its metabolites preferentially inhibit IKr in rabbit ventricular
      myocytes.
AB  - Propafenone is an antiarrhythmic agent with recognized cardiac myocyte
      repolarizing K+ current inhibitory effects. It has two known
      electropharmacologically active metabolites, 5-hydroxy- and N
      depropylpropafenone, whose K+ current inhibitory effects are less thoroughly
      elucidated than those of the parent compound. This study characterizes and
      directly compares the pharmacologic interaction of all three compounds with two
      key repolarizing K+ currents, the rapidly activating delayed rectifier IKr and
      the transient outward current Ito, using the whole-cell patch-clamp technique in
      isolated rabbit ventricular myocytes. All three agents potently inhibited IKr
      with IC50 values of 0.80 +/-0.14, 1.88 +/-0.21, and 5.78 +/-1.24 microM for
      propafenone, 5-hydroxypropafenone, and N-depropylpropafenone, respectively, based
      on reduction of peak tail current amplitude following repolarization from +50 mV
      to -30 mV. IKr inhibition was concentration- and weakly voltage-dependent, with a
      time course from channel activation that was well described by a single
      exponential model and consistent with open channel block. Propafenone and its 5
      hydroxy and N-depropyl metabolites also blocked Ito with IC50 values of 7.27 +/
      0.53, 40.29 +/-7.55, and 44.26 +/-5.73 microM, respectively, at +50 mV. No
      significant drug effects were observed with respect to Ito voltage dependence of
      steady-state inactivation or time course of recovery from inactivation. The
      preferential interaction of propafenone and its metabolites with IKr relative to
      Ito in ventricular myocytes sheds new light on the anti- and proarrhythmic
      activity of propafenone in vivo.

PMID- 14569066
TI  - In vitro discrimination of fluoroquinolones toxicity on tendon cells: involvement
      of oxidative stress.
AB  - Tendinopathy are classic side effects observed with fluoroquinolones antibiotics.
      A previously validated model based on a spontaneously immortalized rabbit tendon
      cell line (Teno cell line) was used to evaluate cellular responses to the
      fluoroquinolones pefloxacin (PEF), ofloxacin (OFX), levofloxacin (LVX), and
      ciprofloxacin (CIP), in various concentrations. Cell viability, redox status
      changes, reduced glutathione content, and reactive oxygen species production were
      assessed using neutral red, Alamar blue, monobromobimane and 2,7
      dichlorofluorescindiacetate fluorescent probes, respectively. Living adherent
      tenocytes were analyzed using a cold light cytofluorometer adapted to 96-well
      microplates. All fluoroquinolones showed moderate cytotoxicity after 24 h and
      more severe, significant toxicity after 72 h on tendon cells. Moreover, two
      groups of fluoroquinolones may be differentiated: intrinsic toxicity for tendon
      cells was high with ciprofloxacin and pefloxacin [redox status decrease was 80
      and 62% (*p < 0.05) for PEF and CIP at 1 mM for 72 h, respectively], but moderate
      with ofloxacin and levofloxacin LVX [redox status decrease was 30 and 22% (*p <
      0.05) for OFX and LVX at 1 mM during 72 h, respectively]. Our model supports a
      role for early oxidative stress in the development of fluoroquinolone-induced
      tendinopathy. Moreover, our study indicates that intrinsic toxicity to tendon
      cells varies across fluoroquinolones. The Teno cell line may be a useful model
      for detecting and evaluating tendon toxicity of new fluoroquinolones and other
      drugs associated with tendinopathy.

PMID- 14569068
TI  - Interaction of cyclooxygenase isoenzymes, nitric oxide, and afferent neurons in
      gastric mucosal defense in rats.
AB  - The cyclooxygenase (COX)-2 inhibitors 5,5-dimethyl-3-(3-fluorophenyl)-4-(4
      methylsulfonyl)phenyl-2(5II)-furanone (DFU) (0.02-2 mg/kg) and N-[2
      (cyclohexyloxy)-4-nitrofenyl]-methanesulfonamide (NS-398) (0.01-1 mg/kg), the COX
      1 inhibitor 5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-trifluoromethylpyrazole (SC
      560) (0.05-5 mg/kg), and dexamethasone (1 mg/kg) were studied in rats challenged
      with intragastric acid (300 mM HCl). All compounds induced severe gastric damage
      when rats were treated concurrently with the inhibitor of constitutive and
      inducible nitric-oxide (NO) synthase N(G)-monomethyl-L-arginine methyl ester (L
      NAME) (3 or 40 mg/kg). DFU and NS-398 caused significantly less damage in rats
      receiving the selective inhibitor of inducible NO synthase N-(3
      (aminomethyl)benzyl)acetamidine (1400W) (0.3 mg/kg). The COX-1 inhibitor SC-560
      induced moderate damage in the acid-challenged stomach even without suppression
      of NO, but damage was aggravated by L-NAME. The COX-3 inhibitor phenacetin (400
      mg/kg) did not injure the gastric mucosa despite suppression of NO. Furthermore,
      DFU, NS-398, SC-560, and dexamethasone caused severe injury in the acid
      challenged stomach of rats pretreated with capsaicin to ablate afferent neurons.
      The mucosal damage induced by the COX-1 inhibitor, the COX-2 inhibitors, and
      dexamethasone in L-NAME- or capsaicin-treated rats was reversed by
      coadministration of 16,16-dimethyl-prostaglandin E2 (2 x 8 ng/kg). Gross mucosal
      damage was paralleled by histology. Our results support the concept that
      endogenous NO, prostaglandins, and afferent neurons act in concert in the
      regulation of gastric mucosal integrity. The prostaglandins necessary for mucosal
      defense in the face of NO suppression, and afferent nerve ablation can be derived
      either from COX-1 or COX-2. The data do not propose a protective role for a
      phenacetin-sensitive COX-3. Our findings suggest that not only COX-1 but also COX
      2 has important functions in the maintenance of gastric integrity.

PMID- 14569069
TI  - Role of multidrug resistance protein 2 (MRP2, ABCC2) in alkylating agent
      detoxification: MRP2 potentiates glutathione S-transferase A1-1-mediated
      resistance to chlorambucil cytotoxicity.
AB  - Our previous studies have shown that the glutathione S-transferases (GSTs) can
      operate in synergy with the efflux transporter multidrug resistance protein 1
      (MRP1, ABCC1) to confer resistance to the cyto- and genotoxicities of some
      anticancer drugs and carcinogens. The current study was designed to determine
      whether the alternative efflux transporter, MRP2 (ABCC2), can also potentiate GST
      mediated detoxifications in HepG2 cells. HepG2 cells, which express high-level
      MRP2 but not MRP1, were stably transduced with GST expression vectors under
      tetracycline-repressible transcriptional control. MRP2 was able to support GSTA1
      1-mediated resistance to chlorambucil (CHB) cytotoxicity in HepG2 cells.
      Resistance was GST isozyme-specific in that GSTP1a-1a and GSTM1a-1a failed to
      confer protection from CHB toxicity. Moreover, inhibition of MRP2 with
      sulfinpyrazone completely reversed GSTA1-1-associated resistance, indicating that
      MRP2-efflux function is required to potentiate GSTA1-1-mediated resistance.
      Relative transport by MRP1 versus MRP2 of monoglutathionyl-CHB (CHB-SG) was
      examined using inside-out plasma membrane vesicles derived from MCF7 cells
      transduced with MRP1 or MRP2 expression vectors. Both MRP1 and MRP2 transported
      CHB-SG efficiently, at the levels of protein expressed, with similar Vmax and
      with Km of 0.39 and 10 microM, respectively. We conclude that detoxification of
      CHB by GSTA1-1 requires the removal of the glutathione conjugate formed and that
      either MRP1 or MRP2 can serve this efflux function. These findings have
      implications for the role of MRP2 in detoxification of alkylating agents in the
      apical epithelium of liver and kidney where it is highly expressed as well as the
      role of MRP2 in the emergence of alkylating drug resistance in cancer cells.

PMID- 14569070
TI  - Modulation of Ca2+ channel currents by a novel antidementia drug N-(4-Acetyl-1
      piperazinyl)-p-fluorobenzamide monohydrate (FK960) in rat hippocampal neurons.
AB  - N-(4-Acetyl-1-piperazinyl)-p-fluorobenzamide monohydrate (FK960), a novel
      antidementia drug, has been demonstrated to ameliorate memory deficits in various
      experimental models of dementia. This drug selectively increases somatostatin
      release from hippocampal slices and augments long-term potentiation (LTP) in the
      CA3 area of the hippocampus. In the present study, the effects of FK960 on
      voltage-activated Ca2+ channels were investigated in acutely isolated rat
      hippocampal neurons, using whole-cell patch-clamp technique to clarify the
      cellular mode of action of FK960. Application of somatostatin significantly
      reduced Ca2+ currents via G protein-coupled signaling pathways. This inhibitory
      effect was significantly abolished by FK960 when applied in combination. In
      contrast, FK960 showed only modest inhibition on the reduction in Ca2+ currents
      produced by baclofen, an agonist of GABAB receptor. Intracellular application of
      the protein kinase inhibitor H-7 did not alter somatostatin-induced inhibition
      and had no significant effect on blockade by FK960. In addition, application of
      FK960 alone produced modest but apparent increases in Ca2+ currents without
      significant changes in the activation kinetics of the channels. The dose-response
      relationship on calcium current enhancement was bell-shaped with a maximum effect
      at 0.1 microM FK960, the same concentration as that for increasing on
      somatostatin release and CA3-LTP. These results show that FK960 reverses G
      protein-dependent inhibition of Ca2+ currents by somatostatin in hippocampal
      neurons. Enhancement of Ca2+ currents by FK960 may be due to its modulatory
      actions on Ca2+ channels, rather than removal of G protein-inhibited tonic
      currents. Together, these mechanisms may be involved in the selective effects of
      FK960 on somatostatin release, excitatory transmission, and synaptic plasticity
      in the hippocampus.

PMID- 14569071
TI  - Inhibition of G protein-coupled and ATP-sensitive potassium currents by 2-methyl
      3-(3,5-diiodo-4-carboxymethoxybenzyl)benzofuran (KB130015), an amiodarone
      derivative.
AB  - 2-Methyl-3- (3,5-diiodo-4-carboxymethoxybenzyl) benzofuran (KB130015; KB), a
      novel compound derived from amiodarone, has been proposed to have antiarrhythmic
      properties. Its effect on the G protein-coupled inward rectifying K+ current
      [IK(ACh) or IK(Ado)], ATP-sensitive K+ current [IK(ATP)], and background inward
      rectifying current (I(K1)) were studied in guinea pig atrial and ventricular
      myocytes by the whole-cell voltage-clamp technique. Receptor-activated
      IK(ACh/Ado), induced in atrial myocytes by the stimulation of either muscarinic
      or Ado receptors was concentration dependently (IC50 value of approximately 0.6
      0.8 microM) inhibited by KB. Receptor-independent guanosine 5'-O-(3
      thio)triphosphate-induced and background IK(ACh), which contributes to the
      resting conductance of atrial myocytes, were equally sensitive to KB (IC50 value
      of approximately 0.9 microM). IK(ATP) induced in atrial myocytes during metabolic
      inhibition with 2,4-dinitrophenol (DNP) was also suppressed by KB, whereas IK1
      measured in ventricular myocytes was insensitive to the drug (KB < or =50
      microM). Although being effective when applied from the outside, intracellular
      application of KB via the patch pipette affected neither IK(ACh) nor IK(ATP).
      3,3',5-triodo-L-thyronin, which shares structural groups with KB, did not have an
      effect on the K+ currents. Consistent with the effects on single myocytes, KB did
      not depolarize the resting potential but antagonized the shortening of action
      potential duration by carbamylcholine-chloride or by DNP in multicellular
      preparations and antagonized the shortening of action potential duration by
      acetylcholine in single myocytes. It is concluded that KB inhibits IK(ACh) and
      IK(ATP) by direct drug-channel interaction at a site more easily accessible from
      extracellular side of the membrane.

PMID- 14569072
TI  - The inhibitory effect of adrenomedullin in the rat ileum: cross-talk with beta3
      adrenoceptor in the serotonin-induced muscle contraction.
AB  - In contrast to vascular muscles, the contribution of a hypotensive peptide
      adrenomedullin (AM) to the regulation of visceral smooth muscles is obscure. The
      content, synthesis, and effects of AM on the muscular tone in rat ileum were
      explored. It was found that there was immunoreactive AM (301 pg/mg of protein)
      and AM mRNA expression (162 fg/pg actin mRNA) in the ileum and that AM evoked
      relaxation in ileal strips (Ki = 0.85 nM) precontracted with serotonin.
      Antagonists of both AM (AM(22-52)) and calcitonin gene-related peptide (CGRP(8
      37)) receptors did not affect this AM-induced relaxation, whereas it was
      suppressed by a selective blocker of beta3-adrenoreceptor (SR 59230A). The AM
      induced relaxation was accompanied by a production of cAMP. Antagonists of
      protein kinases A (KT 5720 and H-7) and an inhibitor of the ATP-dependent K(+)
      channels (glibenclamide) attenuated the effect of AM. We suggest that AM is a
      local regulator of the ileal tone, with an inhibitory action on muscle
      contraction. AM may activate the beta3-adrenoceptors, resulting in protein kinase
      A activation, which in turn opens the ATP-dependent K(+)-channels.

PMID- 14569073
TI  - Antitumor effect of a splenic injection of 5-fluorouracil on metastatic liver
      cancer in mice.
AB  - The regional administration of 5-fluorouracil (5-FU) has been the fundamental
      therapy against liver metastases for the improvement of patient prognosis;
      however, there have been few reports about the immunological effects of this
      agent. It is also unknown whether it affects the spleen, one of the major
      lymphoid organs. The objective of the present study was to determine the
      immunological effect of an intrasplenic injection of 5-FU against liver
      metastases. We investigated the effect of an intrasplenic injection of 5-FU on
      the formation of experimental liver metastasis resulting from an intraportal vein
      injection of colon 26 carcinoma cells in BALB/c mice and elucidated some of the
      underlying mechanisms involving the effects of this on cellular immunity. Liver
      metastases were significantly diminished by the splenic injection of 5-FU,
      particularly in comparison with the portal injection or systemic administration.
      This was followed by augmentation of the interleukin-12 (IL-12) level in the
      spleen and activation of hepatic mononuclear cells. In those cells, NK1.1+ (NKT)
      cells played a central role against metastases. A splenic injection of 5-FU is
      more effective on the involution of liver metastases than portal or systemic
      injection. This effect may be attributed to the augmentation of the IL-12 level
      in the spleen and of NKT cells in the liver rather than to the original effect of
      5-FU, which is the so-called inhibition of DNA synthesis.

PMID- 14569074
TI  - Effect of interferon-gamma on the pharmacokinetics of digoxin, a P-glycoprotein
      substrate, intravenously injected into the mouse.
AB  - P-glycoprotein (P-gp) is an efflux transporter with a wide substrate specificity
      that plays an important role in the disposition of drugs in the epithelial cells
      of various tissues, such as the gastrointestinal tract, liver, and kidney. One
      characteristic feature of this efflux transporter is that its expression and
      activity are modulated by various factors, including cytokines. Here, we
      investigated the effect of interferon-gamma (IFN-gamma) on the transport activity
      of P-gp and its expression in mice, since the cytokine is induced by various
      stimuli and capable of provoking a variety of cellular responses. Twenty-four
      hours after a single intraperitoneal injection of IFN-gamma (1 x 10(5) U), mice
      were intravenously injected with [3H]digoxin, a P-gp substrate, and its
      pharmacokinetics was examined. IFN-gamma pretreatment resulted in retardation of
      plasma elimination of the drug with a concomitant increase of its tissue levels
      in liver, kidney, and intestine. Furthermore, the excretion of [3H]digoxin into
      the urine and bile, but not into the intestinal lumen, was significantly reduced:
      the urinary and biliary excretion clearances in IFN-gamma-treated mice were 65
      and 55%, respectively, of those clearances in untreated mice. However, the P-gp
      expression levels were only slightly reduced (20-30% reduction) by IFN-gamma
      treatment in the liver, kidney, or intestine on Western blot analysis. IFN-gamma
      also caused a slight down-regulation (20-30% reduction) in the expression of
      cytochrome P450 3A (CYP3A) on Western blot analysis. Thus, a more pronounced
      effect may be elicited by IFN-gamma for common substrates of P-gp and CYP3A.

PMID- 14569075
TI  - Central mechanisms regulating penile erection in conscious rats: the dopaminergic
      systems related to the proerectile effect of apomorphine.
AB  - Apomorphine has been used as a pharmacological probe of dopaminergic receptors in
      a variety of central nervous system disorders. The utility of apomorphine as an
      agent for the treatment of erectile dysfunction has also been demonstrated
      clinically. Apomorphine is a nonselective dopaminergic receptor agonist with
      potent binding affinity (Ki) of 101, 32, 26, 2.6, and 10 nM for D1, D2, D3, D4,
      and D5, respectively. When administered either subcutaneously (s.c.) or
      intracerebroventricularly (i.c.v.), apomorphine fully evoked penile erections in
      conscious rats with maximum effect at 0.1 micromol/kg s.c. and 3 nmol/rat i.c.v.,
      respectively. Apomorphine was less efficacious when injected intrathecally (i.t.)
      to L4-L6 spinal levels (50% at 30-100 nmol/rat i.t.). Penile erection facilitated
      by apomorphine was blocked by haloperidol and clozapine (i.p. and i.c.v.) but not
      by domperidone (a peripherally acting dopaminergic receptor antagonist). In this
      model using conscious rats, penile erection was significantly induced by
      quinpirole (D2-D3-D4 receptor agonist), but not by R(+)-1-phenyl-2,3,4,5
      tetrahydro-1H-3-benzazepine-7,8-diol (SKF38393) and R(+)-6-chloro-7,8-dihydroxy-1
      phenyl-2,3,4,5-tetrahydro-1H-3-benzapine (SKF81297) (D1 receptor agonists), or a
      D2 receptor agonist R-5,6-dihydro-N,N-dimethyl-4H-imidazo[4,5,1-ij]quinolin-5
      amine (PNU-95666E). The role of D4 receptors in penile erection was demonstrated
      using selective D4 receptor agonists [(4-phenylpiperazinyl)-methyl]benzamide
      (PD168077) and 5-fluoro-2-[[4-(2-pyridinyl)-1-piperazinyl]methyl]-1H-indole
      (CP226269), whether administered systemically (s.c.) or locally in the brain
      (i.c.v.). The ability of apomorphine to activate D3 receptors in relation to its
      proerectile activity remains to be elucidated by use of selective subtype
      agonists. These results suggest that the proerectile action of apomorphine in
      rats is mediated at supraspinal levels and that this effect is not mimicked by a
      D2 receptor agonist but associated with activation of D4 receptors.

PMID- 14569076
TI  - Evidence that glutathione depletion is a mechanism responsible for the anti
      inflammatory effects of ethyl pyruvate in cultured lipopolysaccharide-stimulated
      RAW 264.7 cells.
AB  - Ethyl pyruvate (EP), an effective scavenger of reactive oxygen species, is also
      an anti-inflammatory agent in a variety of in vivo and in vitro model systems. To
      gain a better understanding of the molecular basis for the anti-inflammatory
      effects of EP, we compared the pharmacological properties of EP andN-acetyl-l
      cysteine (NAC), a well studied scavenger of reactive oxygen species and a
      precursor for the endogenous antioxidant glutathione (GSH). The studies were
      performed using RAW 264.7 murine macrophage-like cells that were stimulated with
      lipopolysaccharide (LPS). Although EP and NAC both inhibited LPS-induced nitric
      oxide and interleukin (IL)-6 secretion, the former compound was considerably more
      potent than the latter. EP markedly inhibited inducible nitric-oxide synthase, IL
      6, and IL-10 mRNA induction, whereas the effects of NAC were minimal. EP
      inhibited LPS-induced nuclear factor-kappaB DNA binding to a much greater extent
      than did NAC. Both compounds inhibited LPS-induced lipid peroxidation, but the
      two compounds had qualitatively different effects on cellular levels of GSH.
      Although NAC increased GSH levels, EP had the opposite effect. The anti
      inflammatory effects of EP were partially reversed when RAW 264.7 cells were
      treated with a cell-permeable GSH analog, glutathione ethyl ester. These data
      support the view that the anti-inflammatory effects of EP are mediated, at least
      in part, by the ability of EP to deplete cellular GSH stores. Moreover, the
      findings presented here suggest that an unusual combination of biochemical
      effects (inhibition of lipid peroxidation and GSH depletion) might account for
      the anti-inflammatory effects of EP.

PMID- 14569077
TI  - Overview: integrating renal hypoxic signals in development and disease.

PMID- 14569078
TI  - Targeting of the VHL-hypoxia-inducible factor-hypoxia-induced gene pathway for
      renal cell carcinoma therapy.
AB  - Treatment of advanced renal cancer has made little progress in the past 30 yr.
      Most clinical efforts have incorporated cytokine-based therapy. The presumption
      has been that the cytokines may trigger a host immune response against the renal
      cancer. Only IFN-alpha and high-dose IL-2 seemed to have positive effects on
      patient outcomes. IFN has prolonged the lives of patients by a few months, and
      high-dose IL-2 is capable of inducing very prolonged remissions (>5 yr) for a
      small number of patients. Nephrectomy in the presence of metastatic disease has
      been established as an effective procedure for select patients, providing
      palliation and prolonging survival. Finally, enthusiasm has focused on the use of
      nonmyeloablative allogeneic stem cell transplantation and donor leukocyte
      infusion for the induction of graft versus tumor effects. Early results are both
      provocative and promising. A number of agents that target the critical gene
      products downstream from pVHL and hypoxia-inducible factor-1, such as vascular
      endothelial growth factor, PDGF, EGF receptor, and TGF-alpha, have recently
      become available. The new agents are capable of inhibiting specific cellular
      targets, and the biologic characteristics of clear cell carcinoma of the kidney
      support their application. If the correct targets are carefully selected for
      inhibition in tumors in which the targets are present (clear cell histologic
      features and loss of VHL expression), then results should resemble those others
      have observed with targeted therapy, such as the use of STI-571 (Gleevec;
      Novartis Pharmaceuticals, East Hanover, NJ) for treatment of chronic myelogenous
      leukemia and gastrointestinal stromal tumors or anti-HER2/neu (Herceptin;
      Genentech, South San Francisco, CA) for treatment of breast cancer.

PMID- 14569079
TI  - The von Hippel-Lindau gene, kidney cancer, and oxygen sensing.
AB  - Recent studies of a relatively rare hereditary cancer syndrome, von Hippel-Lindau
      (VHL) disease, have shed new light on the molecular pathogenesis of kidney cancer
      and, perhaps more important, on how mammalian cells sense and respond to changes
      in oxygen availability. This knowledge is already translating into new
      therapeutic targets for kidney cancer as well as for multiple conditions, such as
      myocardial infarction and stroke, in which ischemia plays a pathogenic role. This
      review summarizes the current knowledge of the molecular pathogenesis of von
      Hippel-Lindau disease and the role of the VHL gene product (pVHL) in kidney
      cancer and the mammalian oxygen sensing pathway.

PMID- 14569080
TI  - HIF-1: an oxygen response system with special relevance to the kidney.

PMID- 14569081
TI  - Hypoxia-inducible factors and kidney vascular development.
AB  - Among the genes strongly induced by hypoxia-inducible factors (HIF) and highly
      expressed during kidney microvascular development is vascular endothelial growth
      factor, which encodes a potent endothelial mitogen and chemoattractant critical
      for embryonic vasculogenesis and angiogenesis. In developing kidney, glomerular
      podocytes are particularly rich sources of vascular endothelial growth factor,
      which probably serves to attract endothelial precursors into vascular clefts of
      immature glomeruli, promote their mitosis and differentiation into glomerular
      endothelial cells, and assist with maintenance of their highly differentiated
      state through maturation. This article summarizes the structure, function, and
      expression of HIF and discusses HIF target genes expressed during kidney vascular
      development. Furthermore, it is speculated that different HIF heterodimers are
      stabilized in different cell populations, which may lead to cell-selective
      induction of HIF target genes important for renal vasculogenesis/angiogenesis.

PMID- 14569082
TI  - Localization and regulation of the epithelial Ca2+ channel TRPV6 in the kidney.
AB  - The family of epithelial Ca(2+) channels consists of two highly homologues
      members, TRPV5 and TRPV6, which constitute the apical Ca(2+) entry mechanism in
      active Ca(2+) (re)absorption in kidney and small intestine. In kidney, TRPV5
      expression has been extensively studied, whereas TRPV6 localization and
      regulation has been largely confined to the small intestine. The present study
      investigated the renal distribution of TRPV6 and regulation by 1,25
      dihydroxyvitamin D(3) (1,25(OH)(2)D(3)). In mouse kidney, TRPV6 was detected by
      immunohistochemistry at the apical domain of the distal convoluted tubules
      (DCT2), connecting tubules (CNT), and cortical and medullary collecting ducts
      (CD). Furthermore, several putative vitamin D-responsive elements were detected
      upstream of the mouse TRPV6 start codon, and 1,25(OH)(2)D(3) treatment
      significantly increased renal TRPV6 mRNA and protein expression. In DCT2 and CNT,
      TRPV6 co-localizes with the other known Ca(2+) transport proteins, including
      TRPV5 and calbindin-D(28K). Together, these data suggest a role for TRPV6 in
      1,25(OH)(2)D(3)-stimulated Ca(2+) reabsorption in these segments. Interestingly,
      distribution of TRPV6 extended to the CD, where it localized to the apical domain
      of principal and intercalated cells, which are not generally implicated in active
      Ca(2+) reabsorption. In addition, TRPV6 mRNA levels were quantified in a large
      set of tissues, and in the order of decreasing expression level were detected:
      prostate > stomach, brain > lung > duodenum, kidney, bone, cecum, heart > colon >
      skeletal muscle > pancreas. Therefore, additional physiologic functions for TRPV6
      are feasible. In conclusion, TRPV6 is expressed along the apical domain of DCT2,
      CNT, and CD, where TRPV6 expression is positively regulated by 1,25(OH)(2)D(3).

PMID- 14569083
TI  - Impaired renal secretion of substrates for the multidrug resistance protein 2 in
      mutant transport-deficient (TR-) rats.
AB  - Previous studies with mutant transport-deficient rats (TR(-)), in which the
      multidrug resistance protein 2 (Mrp2) is lacking, have emphasized the importance
      of this transport protein in the biliary excretion of a wide variety of
      glutathione conjugates, glucuronides, and other organic anions. Mrp2 is also
      present in the luminal membrane of proximal tubule cells of the kidney, but
      little information is available on its role in the renal excretion of
      xenobiotics. The authors compared renal transport of the fluorescent Mrp2
      substrates calcein, fluo-3, and lucifer yellow (LY) between perfused kidneys
      isolated from Wistar Hannover (WH) and TR(-) rats. Isolated rat kidneys were
      perfused with 100 nM of the nonfluorescent calcein-AM or 500 nM fluo3-AM, which
      enter the tubular cells by diffusion and are hydrolyzed intracellularly into the
      fluorescent anion. The urinary excretion rates of calcein and fluo-3 were 3 to 4
      times lower in perfused kidneys from TR(-) rats compared with WH rats. In
      contrast, the renal excretion of LY (10 micro M, free anion) was somewhat delayed
      but appeared unimpaired in TR(-) rats. Membrane vesicles from Sf9 cells
      expressing human MRP2 or human MRP4 indicated that MRP2 exhibits a preferential
      affinity for calcein and fluo-3, whereas LY is a better substrate for MRP4. We
      conclude that the renal clearance of the Mrp2 substrates calcein and fluo-3 is
      significantly reduced in TR(-) rat; for LY, the absence of the transporter may be
      compensated for by (an)other organic anion transporter(s).

PMID- 14569085
TI  - Urea restrains aldosterone-induced development of peanut agglutinin-binding on
      embryonic renal collecting duct epithelia.
AB  - Peanut agglutinin (PNA) represents a commonly used marker for beta-type
      intercalated (IC) cells and their distribution in the corticomedullary course of
      the collecting duct (CD) in the mature rabbit kidney. It has been shown that
      aldosterone is able to generate >90% of PNA-binding cells in an embryonic CD
      epithelium in vitro. In adult kidney, a maximum of only 25% PNA-positive cells is
      found in the cortical segment of the CD, and PNA-binding completely disappears in
      the inner-medullary CD. Molecules that regulate the gradual development of CD
      specific cells during organ growth are unknown. In the present experiments, it
      was found that addition of physiologic concentrations of urea to the culture
      medium is able to restrain the action of aldosterone in embryonic CD epithelia.
      Urea antagonizes in a concentration-dependent manner the action of aldosterone
      finally leading to only 10% of PNA-binding cells. The data point to a urea
      specific effect, because osmolytes such as NaCl and mannitol did not affect PNA
      binding. In addition, urea did not influence expression of principal-cell typical
      markers such as AQP2 and 3. The findings may explain that a higher number of PNA
      positive cells is found in the cortical region of the kidney correlated with a
      low concentration of urea as compared with only few PNA-binding cells in the
      medullary CD, where a high concentration of urea occurs. Thus, an increasing
      concentration of urea may trigger the number of PNA-positive cells in the
      cortical-medullary course of the CD during organ development.

PMID- 14569084
TI  - Inhibition of erythrocyte cation channels by erythropoietin.
AB  - Recombinant human erythropoietin therapy is used to counteract anemia that is the
      result of renal insufficiency. It stimulates the formation of peripheral blood
      erythrocytes by inhibiting apoptosis of erythrocyte precursor cells. Mature
      erythrocytes have similarly been shown to undergo apoptosis. Hyperosmotic shock
      and Cl(-) removal activate a Ca(2+)-permeable, ethylisopropylamiloride
      inhibitable cation channel. The subsequent increase of cytosolic Ca(2+) activates
      a scramblase that breaks down cell membrane phosphatidylserine asymmetry, leading
      to annexin binding. Studied was whether channel activity and erythrocyte cell
      death are regulated by erythropoietin. Scatchard plot analysis disclosed low
      abundance, high-affinity binding of (125)I-erythropoietin to erythrocytes. Whole
      cell patch clamp experiments revealed significant inhibition of the
      ethylisopropylamiloride-sensitive current by 1 U/ml erythropoietin. Cl(-) removal
      triggered annexin binding, an effect abrogated by erythropoietin (1 U/ml) but not
      by GM-CSF (10 ng/ml). Osmotic shock (700 mOsm) stimulated annexin binding within
      24 h in the majority of the erythrocytes, an effect blunted by erythropoietin (1
      U/ml) but not by GM-CSF (10 ng/ml). In the nominal absence of Ca(2+), the effect
      of osmotic shock was blunted and the effect of erythropoietin abolished. In
      hemodialysis patients, intravenous administration of erythropoietin (50 IU/kg)
      within 4 h decreased the number of annexin binding circulating erythrocytes.
      Erythropoietin binds to erythrocytes and inhibits volume-sensitive erythrocyte
      cation channels and thus the breakdown of phosphatidylserine asymmetry after
      activation of this channel. The effect could prolong the erythrocyte lifespan and
      may contribute to the enhancement of the erythrocyte number during erythropoietin
      therapy in dialysis patients.

PMID- 14569086
TI  - Ureteric bud apoptosis and renal hypoplasia in transgenic PAX2-Bax fetal mice
      mimics the renal-coloboma syndrome.
AB  - In humans, PAX2 haploinsufficiency causes renal-coloboma syndrome (RCS) involving
      eye abnormalities, renal hypoplasia, and renal failure in early life. The authors
      previously showed that heterozygous mutant Pax2 mice have smaller kidneys with
      fewer nephrons, associated with elevated apoptosis in the ureteric bud (UB).
      However, PAX2 may have a variety of developmental functions such as effects on
      cell fate and differentiation. To determine whether apoptosis alone is sufficient
      to cause a UB branching deficit, the authors targeted a pro-apoptotic gene
      (Baxalpha) to the embryonic kidney under the control of human PAX2 regulatory
      elements. The exogenous PAX2 promoter directed Baxalpha gene expression
      specifically to the developing kidney UB, eye, and mid/hindbrain. At E15.5
      PAX2Promoter-Baxalpha fetal mice exhibited renal hypoplasia, elevated UB
      apoptosis, and retinal defects, mimicking the phenotype observed in RCS. The
      kidneys of E15.5 PAX2Promoter-Baxalpha fetal mice were 55% smaller than those of
      wild-type fetal mice, and they contained 70% of the normal level of UB branching.
      The data indicate that loss of Pax2 anti-apoptotic activity is sufficient to
      account for the reduced UB branching observed in RCS and suggest that elevated UB
      apoptosis may be a key process responsible for renal hypoplasia. The authors
      propose a morphogenic unit model in which cell survival influences the rate of UB
      branching and determines final nephron endowment.

PMID- 14569087
TI  - Salt intake, oxidative stress, and renal expression of NADPH oxidase and
      superoxide dismutase.
AB  - The hypothesis that a high salt (HS) intake increases oxidative stress was
      investigated and was related to renal cortical expression of NAD(P)H oxidase and
      superoxide dismutase (SOD). 8-Isoprostane PGF(2alpha) and malonyldialdehyde were
      measured in groups (n = 6 to 8) of conscious rats during low-salt, normal-salt,
      or HS diets. NADPH- and NADH-stimulated superoxide anion (O(2)(.-)) generation
      was assessed by chemiluminescence, and expression of NAD(P)H oxidase and SOD were
      assessed with real-time PCR. Excretion of 8-isoprostane and malonyldialdehyde
      increased incrementally two- to threefold with salt intake (P < 0.001), whereas
      prostaglandin E(2) was unchanged. Renal cortical NADH- and NADPH-stimulable
      O(2)(.-) generation increased (P < 0.05) 30 to 40% with salt intake. Compared
      with low-salt diet, HS significantly (P < 0.005) increased renal cortical mRNA
      expression of gp91(phox) and p47(phox) and decreased expression of intracellular
      CuZn (IC)-SOD and mitochondrial (Mn)-SOD. Despite suppression of the renin
      angiotensin system, salt loading enhances oxidative stress. This is accompanied
      by increased renal cortical NADH and NADPH oxidase activity and increased
      expression of gp91(phox) and p47(phox) and decreased IC- and Mn-SOD. Thus, salt
      intake enhances generation of O(2)(.-) accompanied by enhanced renal expression
      and activity of NAD(P)H oxidase with diminished renal expression of IC- and Mn
      SOD.

PMID- 14569088
TI  - Role of oxidative stress in endothelial dysfunction and enhanced responses to
      angiotensin II of afferent arterioles from rabbits infused with angiotensin II.
AB  - The hypothesis that O(2)(.-) enhances angiotensin II (AngII)-induced
      vasoconstriction and impairs acetylcholine-induced vasodilation of afferent
      arterioles (Aff) in AngII-induced hypertension was investigated. Rabbits (n = 6
      per group) received 12 to 14 d of 0.154 M NaCl (Sham), subpressor AngII (60 ng/kg
      per min; AngII 60) or slow pressor AngII (200 ng/kg per min; AngII 200).
      Individual Aff were perfused in vitro at 60 mmHg. AngII 200 increased mean
      arterial pressure (mean +/- SD; 103 +/- 9 versus 73 +/- 6 mmHg; P < 0.01), plasma
      lipid peroxides (2.6 +/- 0.3 versus 2.0 +/- 0.3 nM; P < 0.05), renal cortical
      NADPH- and NADH-dependent O(2)(.-) generation, and Aff mRNA for p22(phox) 5-fold
      (P < 0.001) but decreased that for AT(1)-receptor 2.4-fold (P < 0.01). AngII 60
      increased only NADH-dependent O(2)(.-) generation by renal cortex. Aff from AngII
      200 rabbits had diminished acetylcholine relaxations (+50 +/- 4 versus +85 +/-
      6%; P < 0.001), but these became similar in the presence of nitro-L-arginine (10(
      4) M). Aff from AngII 60 and AngII 200 rabbits had unchanged norepinephrine
      contractions (10(-7) M) but significantly (P < 0.05) enhanced AngII contractions
      (10(-8) M: Sham -52 +/- 5 versus AngII 60 to 77 +/- 5 versus AngII 200 to 110 +/-
      10%). The superoxide dismutase mimetic tempol (10(-4) M) moderated the AngII
      responses of Aff from AngII 200 rabbits to levels of AngII 60 rabbits (-64 +/-
      7%). The AngII slow pressor response enhances renal cortical O(2)(.-) and
      p22(phox) expression. Increased O(2)(.-) generation in Aff mediates an impaired
      nitric oxide synthase-dependent endothelium-derived relaxing factor response and
      paradoxically enhances contractions to AngII despite downregulation of the mRNA
      for AT(1) receptors. A subpressor dose of AngII enhances Aff responses to AngII
      independent of O(2)(.-).

PMID- 14569089
TI  - Nitric oxide inhibits stretch-induced MAPK activation in mesangial cells through
      RhoA inactivation.
AB  - Glomerular capillary hypertension is an important determinant of
      glomerulosclerosis in rats with subtotal renal ablation. Dietary supplementation
      with L-arginine increases renal nitric oxide (NO) production and limits
      glomerular injury in this model, and early benefits are seen without altered
      glomerular capillary pressure. In an in vitro model of hemodynamically mediated
      signaling, the authors have reported that subjecting MC to cyclic
      stretch/relaxation activates the mitogen-activated protein kinase p42/44 (Erk)
      cascade and that NO and cyclic GMP abrogate stretch-induced Erk activation by
      inducing actin cytoskeletal disassembly. The actin cytoskeleton is regulated by
      the Rho family of GTPases, including RhoA; therefore, the authors examined the
      role of RhoA in stretch-induced Erk activation and as an NO target. In primary
      rat MC subjected to cyclic mechanical strain, RhoA activity was maximally
      increased (2.4-fold) after 1 min of stretch, and Erk activation temporally
      followed. The Rho-kinase inhibitor Y-27632 attenuated Erk activation in a dose
      dependent manner and prevented stretch-induced actin stress fiber formation. The
      NO donors S-nitroso-N-acetylpenicillamine and cGMP both inhibited stretch-induced
      RhoA and Erk activation and stress fiber formation. Infection of MC with the RhoA
      mutant RhoA-Ala188, which is resistant to NO-dependent phosphorylation, abrogated
      the effects of NO and cGMP on stretch-induced Erk activation and stress fiber
      formation. The authors conclude that the early activation of RhoA is essential
      for stretch-induced actin stress fiber formation and Erk activation in MC, events
      which are prevented by NO and cGMP through their action on RhoA. Inhibition of
      RhoA may thus be a new approach to the prevention of hemodynamically mediated
      glomerular injury.

PMID- 14569090
TI  - The fine specificity and cytokine profile of T-helper cells responsive to the
      alpha3 chain of type IV collagen in Goodpasture's disease.
AB  - Goodpasture's disease is a severe nephritis characterized by autoantibodies to
      the alpha3 chain of type IV collagen, alpha3(IV)NC1, in the glomerular basement
      membrane. The disease is very strongly associated with HLA-DR15, the affinities
      of alpha3(IV)NC1 peptides for DR15 are known, and elution experiments have
      identified major naturally processed sequences. Here, the fine specificity and
      cytokine profile of alpha3(IV)NC1-reactive T cells from patients with
      Goodpasture's disease is defined. Peripheral blood mononuclear cells from
      patients at diagnosis proliferated in response to significantly more peptides
      (chi(2) = 8.6, P = 0.004) from a panel spanning the sequence of alpha3(IV)NC1
      than did those from control DR15-positive donors and were highly focused (P =
      0.0002, binomial distribution) on two peptides, alpha3(71-90) and alpha3(131
      150). Some peptides induced interferon-gamma, but none induced IL-4. Resolution
      of disease was accompanied by a striking deviation of the responses from
      proliferation to secretion of the T-regulatory cytokine IL-10, and addition of
      neutralizing antibody confirmed that such IL-10 production was suppressive. The
      affinity of the peptides for DR15 molecules was positively correlated (chi(2) =
      14.6, P = 0.00067) with the ability to elicit proliferation. However, unlike
      foreign antigens, this hierarchy is not due to responses against the major
      naturally processed peptides, which rarely stimulated proliferation and which
      have only intermediate affinity for DR15 molecules. It is inferred that the
      helper response to alpha3(IV)NC1 in Goodpasture's disease is dominated by
      epitopes that are normally inefficiently presented because of processing
      constraints.

PMID- 14569091
TI  - Intrinsic renal cell expression of CD40 directs Th1 effectors inducing
      experimental crescentic glomerulonephritis.
AB  - Evidence suggests that human and experimental crescentic GN results from Th1
      predominant immunity to glomerular antigens. CD40/CD154 signaling plays a key
      role in initiating Th1 responses and may direct Th1 effector responses. The role
      of CD40 in the development of GN was assessed in murine experimental anti
      glomerular basement membrane GN. In this model, C57BL/6 wild-type (WT) mice
      sensitized to sheep globulin develop crescentic GN resulting from Th1 effector
      responses when challenged with sheep globulin planted in glomeruli. CD40-/- mice
      do not develop immunity in response to sheep globulin and thus fail to develop
      effector responses or significant GN. CD40 is expressed in nephritic glomeruli,
      suggesting a potential role for intrarenal CD40-CD154 interactions in injurious
      effector responses. Immune neutralization of the CD40 ligand (CD154) at the time
      of challenge significantly reduced accumulation of Th1 effectors and injury. The
      role of CD40 expression by renal cells was assessed by comparing GN in WT-->CD40
      /- chimeras (absent renal but intact bone marrow CD40) and sham chimeric mice (WT
      ->WT). Both groups developed strong antigen-specific immune responses (antibody
      and IFN-gamma production). However, WT-->CD40-/- chimeras demonstrated reduced
      renal monocyte chemotactic protein 1 and IFN-inducible protein 10 mRNA levels and
      minimal T cell and macrophage influx and were protected from renal injury. Sham
      chimeric mice developed reduced GFR, with prominent renal expression of monocyte
      chemotactic protein 1 and IFN-inducible protein 10 mRNA and effector cell
      accumulation. In conclusion, the expression of CD40 by nonimmune renal cells
      plays a major role in Th1 effector responses by inducing Th1 chemokine
      production. Therefore, CD40-CD154 interactions are a potential therapeutic target
      in GN.

PMID- 14569092
TI  - Differential usage of class II transactivator promoters PI and PIV during
      inflammation and injury in kidney.
AB  - Expression of class II transactivator (CIITA), the transcriptional regulator that
      controls all class II expression, is controlled in cell lines in vitro by three
      promoters: the dendritic cell promoter PI, the B cell promoter PIII, and the
      interferon-gamma (IFN-gamma)-inducible promoter, PIV. The authors examined the
      promoter usage in vivo in mouse kidney in the basal state and in response to IFN
      gamma, endotoxin, allostimulation, and renal injury. Genetically modified mice
      were used to examine the dependency of each promoter on IFN-gamma and on the
      transcription factor interferon regulatory factor 1 (IRF-1). Usage of distinct
      CIITA promoters was monitored by real-time reverse transcriptase polymerase chain
      reaction (RT-PCR) using the unique sequences in the 5' end of the transcript from
      each promoter. Kidneys in both control mice and IFN-gamma knockouts expressed
      chiefly PI- and PIV-related products. Administration of recombinant IFN-gamma
      activated only promoter PIV. Endotoxin or allogeneic stimulation elevated the PIV
      related mRNA, dependent on IFN-gamma and on IRF-1. Ischemic renal injury,
      however, increased the PI- and PIV-driven mRNA expression in wild-type but also
      in IFN-gamma-deficient mice. Thus the in vivo control of CIITA promoters in
      kidney is similar to that observed in vitro (i.e., basal-state usage of PI and
      IFN-gamma-dependent usage of PIV during inflammation), but it also shows
      additional levels of control: IFN-gamma-independent basal activity of PIV and IFN
      gamma-independent induction of PIV during tissue injury.

PMID- 14569093
TI  - Reversal of glomerulosclerosis after high-dose enalapril treatment in subtotally
      nephrectomized rats.
AB  - Interventions to block the renin-angiotensin system (RAS) halt the progression of
      renal lesions in renal damage models. It has recently also been reported that
      established glomerulosclerosis can be reversed by pharmacologic blockade of the
      RAS. It was the aim of this study to confirm that high doses of angiotensin
      converting enzyme (ACE) inhibitors reverse established glomerulosclerosis and to
      extend the findings by providing quantitative information on glomerular geometry,
      podocytes and other glomerular cells, renal vessels and tubulointerstitial
      tissue. Male Sprague Dawley rats were subjected to subtotal surgical renal
      ablation (SNX) (n = 27) or sham operation (n = 31) and fed using a pair-feeding
      protocol. Eight weeks after surgery, rats were either sacrificed or allocated to
      two arms: enalapril treatment (48 mg/kg body wt per day administered in the
      drinking fluid for 4 wk) or no treatment. Renal morphology was evaluated after 8
      or 12 wk, respectively, by stereology in tissue fixed by pressure-controlled
      perfusion. Both systolic BP and albumin excretion rate were significantly higher
      in SNX compared with sham-operated controls. They were significantly reduced in
      SNX after delayed enalapril treatment. The glomerulosclerosis (GSI),
      tubulointerstitial (TII), and vascular (VI) damage indices were significantly
      higher in all SNX groups than in sham-operated controls. At the end of the
      experiment (12 wk after SNX) GSI, TII, and VI were significantly lower in SNX
      with delayed enalapril treatment (0.77 +/- 0.18, 0.63 +/- 0.19 and 0.43 +/- 0.16,
      respectively) compared with untreated SNX (1.64 +/- 0.14, 1.16 +/- 0.34 and 0.67
      +/- 0.29, respectively). GSI, TII, and VI were also significantly lower in SNX
      with delayed enalapril treatment compared with SNX sacrificed without treatment 8
      wk after SNX. The same was true for glomerular volume. The number of podocytes
      was not affected by SNX, but podocyte volume was increased. Both indices remained
      unaffected by treatment. The numbers of cells within the mesangium and
      endothelial cells per glomerulus were significantly lower in SNX after delayed
      enalapril treatment compared with untreated SNX. These results strongly suggest
      regression of preexisting lesions, i.e., glomerular, tubular, and vascular
      remodeling as well as reversal of glomerular hypertrophy by ACE inhibitor
      treatment. The study confirms that high-dose ACE inhibitor treatment causes
      partial reversal of glomerular as well as interstitial lesions in subtotally
      nephrectomized rats.

PMID- 14569095
TI  - Hemodialysis and peritoneal dialysis: comparison of adjusted mortality rates
      according to the duration of dialysis: analysis of The Netherlands Cooperative
      Study on the Adequacy of Dialysis 2.
AB  - Various studies indicate that fair comparisons of mortality rates between
      hemodialysis (HD) patients and peritoneal dialysis (PD) patients are difficult
      because of differences in patient characteristics, because of nonconstant
      relative risks of death (RR), and because the survival times of patients who
      switch treatment modalities can be censored in different ways. The differences in
      mortality rates between HD and PD patients were investigated in an analysis in
      which these potential sources of bias were taken into account. The Netherlands
      Cooperative Study on the Adequacy of Dialysis is a multicenter, prospective,
      observational, cohort study in which new patients with ESRD are monitored until
      transplantation or death. A multivariate Cox regression analysis was used to
      analyze the mortality data according to treatment modality (HD, n = 742; PD, n =
      480). No statistically significant differences in adjusted mortality rates
      between HD and PD patients were observed during the first 2 yr of dialysis. In
      the years thereafter, increases in mortality rates for PD patients and resulting
      decreases in RR in favor of HD were observed (e.g., months 24 to 36, adjusted RR,
      0.53; 95% confidence interval, 0.31 to 0.91). This tendency was observed
      especially among patients >/=60 yr of age and was not influenced by the censoring
      strategy. These results suggest that long-term use of PD, especially among
      elderly patients, is associated with increases in mortality rates. Further
      analyses are required to determine the potential role of dialysis adequacy in the
      observed long-term differences in mortality rates between HD and PD patients and
      to establish the possible survival benefits for PD patients who switch to HD in
      time.

PMID- 14569094
TI  - Genetic variation in the Renin-Angiotensin system and progression of diabetic
      nephropathy.
AB  - The impact of polymorphisms in the genes coding for angiotensinogen (M235T), ACE
      (ID), and angiotensin II type 1 receptor (A(1166)-->C) on decline in GFR and
      doubling of s-creatinine or development of ESRD in patients with type 1 diabetes
      and diabetic nephropathy (DN) was tested. From 1985, all patients (n = 169) who
      had established diabetic nephropathy and were treated with angiotensin-converting
      enzyme inhibition (ACE-I) were identified consecutively at Steno Diabetes Center.
      Patients were followed for a median of 6 yr (range, 3 to 15 yr), with nine
      (range, three to 29) measurements of GFR ((51)Cr-EDTA). In a Cox proportional
      hazards model corrected for other risk factors, the D allele (ACE/ID) was
      associated with time to doubling of s-creatinine/ESRD (rate ratio, 1.81 per
      allele; 95% confidence interval, 1.09 to 3.03; P = 0.02). A new interaction
      hypothesis was generated demonstrating that the following variables were
      associated with accelerated decline in GFR: albuminuria (estimate, 2.12 ml/min
      per yr per 10-fold increase in albuminuria; P < 0.001), mean BP (estimate, 0.88
      ml/min per yr per 10 mmHg; P = 0.02), hemoglobin A(1c) (estimate, 0.54 min/min
      per yr per 1%; P = 0.02), and number of M (M235T)/D (ID)/A (A(1166)-->C) alleles
      (estimate, 0.45 ml/min per yr per allele; P = 0.049). Number of M/D/A alleles
      also influenced time to doubling of s-creatinine or ESRD. In this study of
      patients with type 1 diabetes, the D allele of the ACE/ID polymorphism in
      addition to nongenetic risk factors independently accelerated progression of DN
      during ACE-I. Interaction between polymorphisms in the renin-angiotensin system
      also influenced the loss of kidney function. This new genetic interaction model
      needs to be confirmed in future studies.

PMID- 14569096
TI  - Angiotensin-converting enzyme inhibition but not angiotensin II receptor blockade
      regulates matrix metalloproteinase activity in patients with glomerulonephritis.
AB  - Equivalent long-term effects on the kidney are attributed to angiotensin
      converting enzyme inhibitors (ACEI) and angiotensin II type 1 receptor blockers
      (ARB). Nevertheless, it is unknown to which degree effects of these compounds on
      individual inflammatory mediators, including matrix metalloproteinases (MMP), are
      comparable. On the basis of structural and functional differences, it was
      hypothesized that ACEI and ARB differentially regulate MMP activity. In a
      randomized, prospective crossover trial, the effect of an ACEI (fosinopril; 20
      mg/d) and of an ARB (irbesartan; 150 mg/d) on MMP activity was evaluated. Ten
      hypertensive patients with glomerulonephritis and normal or mildly reduced
      creatinine clearance were studied. MMP activity and tissue inhibitors of
      metalloproteinase (TIMP) levels were analyzed in serum and urine: without
      therapy, with ACEI, with ARB, and with both agents combined. Treatment periods
      continued for 6 wk separated by periods of 4 wk each without therapy. Untreated
      patients with glomerulonephritis displayed distinctively higher serum levels of
      MMP-2 but much lower MMP-1/-8/-9 concentrations compared with healthy control
      subjects. Immunohistology of MMP-2 and MMP-9 in kidney biopsy specimen was
      accordingly. However, these patients excreted higher amounts of MMP-2 and MMP-9
      in urine than healthy control subjects, possibly reflecting ongoing glomerular
      inflammation. In patients with glomerulonephritis, ACEI significantly reduced
      overall MMP serum activity to 25%, whereas ARB did not show any effect.
      Activities of MMP-1/-2/-8/-9 were also significantly inhibited by fosinopril but
      not by irbesartan. Levels of TIMP-1/-2 remained unaffected. In conclusion, ACEI
      and ARB differentially regulate MMP activity, which may ultimately have
      consequences in certain types of MMP-dependent glomerulonephritis.

PMID- 14569097
TI  - Molecular analysis of the SGLT2 gene in patients with renal glucosuria.
AB  - The role of SGLT2 (the gene for a renal sodium-dependent glucose transporter) in
      renal glucosuria was evaluated. Therefore, its genomic sequence and its intron
      exon organization were determined, and 23 families with index cases were analyzed
      for mutations. In 21 families, 21 different SGLT2 mutations were detected. Most
      of them were private; only a splice mutation was found in 5 families of different
      ethnic backgrounds, and a 12-bp deletion was found in two German families.
      Fourteen individuals (including the original patient with 'renal glucosuria type
      0') were homozygous or compound heterozygous for an SGLT2 mutation resulting in
      glucosuria in the range of 14.6 to 202 g/1.73 m(2)/d (81 - 1120 mmol/1.73
      m(2)/d). Some, but not all, of their heterozygous family members had an increased
      glucose excretion of up to 4.4 g/1.73 m(2)/d (24 mmol/1.73 m(2)/d). Likewise, in
      index cases with glucosuria below 10 g/1.73 m(2)/d (55 mmol/1.73 m(2)/d) an SGLT2
      mutation, if present, was always detected in the heterozygous state. We conclude
      that SGLT2 plays an important role in renal tubular glucose reabsorption.
      Inheritance of renal glucosuria shows characteristics of a codominant trait with
      variable penetrance.

PMID- 14569098
TI  - A cluster of mutations in the UMOD gene causes familial juvenile hyperuricemic
      nephropathy with abnormal expression of uromodulin.
AB  - Familial juvenile hyperuricemic nephropathy (FJHN [MIM 162000]) is an autosomal
      dominant disorder characterized by abnormal tubular handling of urate and late
      development of chronic interstitial nephritis leading to progressive renal
      failure. A locus for FJHN was previously identified on chromosome 16p12 close to
      the MCKD2 locus, which is responsible for a variety of autosomal-dominant
      medullary cystic kidney disease (MCKD2). UMOD, the gene encoding the Tamm
      Horsfall/uromodulin protein, maps within the FJHN/MCKD2 critical region.
      Mutations in UMOD were recently reported in nine families with FJHN/MCKD2
      disease. A mutation in UMOD has been identified in 11 FJHN families (10 missense
      and one in-frame deletion)-10 of which are novel-clustering in the highly
      conserved exon 4. The consequences of UMOD mutations on uromodulin expression
      were investigated in urine samples and renal biopsies from nine patients in four
      families. There was a markedly increased expression of uromodulin in a cluster of
      tubule profiles, suggesting an accumulation of the protein in tubular cells.
      Consistent with this observation, urinary excretion of wild-type uromodulin was
      significantly decreased. The latter findings were not observed in patients with
      FJHN without UMOD mutations. In conclusion, this study points to a mutation
      clustering in exon 4 of UMOD as a major genetic defect in FJHN. Mutations in UMOD
      may critically affect the function of uromodulin, resulting in abnormal
      accumulation within tubular cells and reduced urinary excretion.

PMID- 14569099
TI  - Obesity is associated with worse peritoneal dialysis outcomes in the Australia
      and New Zealand patient populations.
AB  - Although obesity is associated with increased risks of morbidity and death in the
      general population, a number of studies of patients undergoing hemodialysis have
      demonstrated that increasing body mass index (BMI) is correlated with decreased
      mortality risk. Whether this association holds true among patients treated with
      peritoneal dialysis (PD) has been less well studied. The aim of this
      investigation was to examine the association between BMI and outcomes among new
      PD patients in a large cohort, with long-term follow-up monitoring. Using data
      from the Australia and New Zealand Dialysis and Transplant Registry, an analysis
      of all new adult patients (n = 9679) who underwent an episode of PD treatment in
      Australia or New Zealand between April 1, 1991, and March 31, 2002, was
      performed. Patients were classified as obese (BMI of >/=30 kg/m(2)), overweight
      (BMI of 25.0 to 29.9 kg/m(2)), normal weight (BMI of 20 to 24.9 kg/m(2)), or
      underweight (BMI of <20 kg/m(2)). In multivariate analyses, obesity was
      independently associated with death during PD treatment (hazard ratio, 1.36; 95%
      confidence interval, 1.14 to 1.54; P < 0.05) and technique failure (hazard ratio,
      1.17; 95% confidence interval, 1.07 to 1.26; P < 0.01), except among patients of
      New Zealand Maori/Pacific Islander origin, for whom there was no significant
      relationship between BMI and death during PD treatment. A supplementary
      fractional polynomial analysis modeled BMI as a continuous predictor and
      indicated a J-shaped relationship between BMI and patient mortality rates and a
      steady increase in death-censored technique failure rates up to a BMI of 40
      kg/m(2); the mortality risk was lowest for BMI values of approximately 20
      kg/m(2). In conclusion, obesity at the commencement of renal replacement therapy
      is a significant risk factor for death and technique failure. Such patients
      should be closely monitored during PD and should be considered for early transfer
      to an alternative renal replacement therapy if difficulties are experienced.

PMID- 14569100
TI  - Racial differences in the progression from chronic renal insufficiency to end
      stage renal disease in the United States.
AB  - Black Americans experience a disproportionate burden of ESRD compared with
      whites. Whether this is caused by the increased prevalence of chronic renal
      insufficiency (CRI) among blacks or by their increased progression from CRI to
      ESRD was investigated. A birth cohort analysis was performed using data from the
      Third National Health and Nutrition Examination Survey and the United States
      Renal Data System. It was assumed that those who developed ESRD in 1996 aged 25
      to 79 yr came from the source population with CRI aged 20 to 74 yr that was
      sampled in the Third National Health and Nutrition Examination Survey (midpoint
      1991). GFR was estimated using the Modification of Diet in Renal Disease study
      equation. The prevalence of CRI (GFR 15 to 59 ml/min per 1.73 m(2)) was not
      different among black compared with white adults (2060 versus 2520 per 100,000; P
      = 0.14). For each 100 blacks with CRI in 1991, five new cases of ESRD developed
      in 1996, whereas only one case of ESRD developed per 100 whites with CRI (risk
      ratio, 4.8; 95% confidence interval, 2.9 to 8.4). The increased risk for blacks
      compared with whites was only modestly affected by adjustment for age, gender,
      and diabetes. Blacks with CRI had higher systolic (147 versus 136 mmHg; P =
      0.001) and diastolic (82 versus 77 mmHg; P = 0.02) BP and greater albuminuria
      (422 versus 158 micro g urine albumin/mg urine creatinine; P = 0.01). The higher
      incidence of ESRD among blacks is not due to a greater prevalence of CRI among
      blacks. The key to understanding black-white differences in ESRD incidence lies
      in understanding the extreme differences in their progression from CRI to ESRD.

PMID- 14569101
TI  - Hepatitis C and renal transplantation in the era of modern immunosuppression.
AB  - Kidneys from donors who are positive for hepatitis C virus (DHCV+) have recently
      been identified as an independent risk factor for mortality after renal
      transplantation. However, it has not been determined whether risk persists after
      adjustment for baseline cardiac comorbidity or applies in the era of modern
      immunosuppression. Therefore, a historical cohort study was conducted of US adult
      cadaveric renal transplant recipients from January 1, 1996, to May 31, 2001;
      followed until October 31, 2001. A total of 36,956 patients had valid donor and
      recipient HCV serology. Cox regression analysis was used to model adjusted hazard
      ratios for mortality and graft loss, respectively, adjusted for other factors,
      including comorbid conditions from Center for Medicare and Medicaid Studies Form
      2728 and previous dialysis access-related complications. It was found that DHCV+
      was independently associated with an increased risk of mortality (adjusted hazard
      ratio, 2.12, 95% confidence interval, 1.72 to 2.87; P < 0.001), primarily as a
      result of infection. Mycophenolate mofetil was associated with improved survival
      in DHCV+ patients, primarily related to fewer infectious deaths. Adjusted
      analyses limited to recipients who were HCV+, HCV negative, or age 65 and over,
      or by use of mycophenolate mofetil confirmed that DHCV+ was independently
      associated with mortality in each subgroup. It is concluded that DHCV+ is
      independently associated with an increased risk of mortality after renal
      transplantation adjusted for baseline comorbid conditions in all subgroups.
      Recipients of DHCV+ organs should be considered at high risk for excessive
      immunosuppression.

PMID- 14569102
TI  - Association of high serum creatinine and anemia increases the risk of coronary
      events: results from the prospective community-based atherosclerosis risk in
      communities (ARIC) study.
AB  - Coronary heart disease (CHD) is a major cause of morbidity and mortality in
      patients with chronic kidney disease or anemia. The purpose of this study was to
      examine whether the association between renal function and risk of CHD is
      modified by hemoglobin (Hgb) status. Analyses were based on data from the
      Atherosclerosis Risk in Communities study, a community-based study of risk
      factors for CHD in middle-aged people. People with known CHD at baseline were
      excluded from the analysis. Participants were followed for 9 yr for the
      occurrence of CHD. Anemia was defined as Hgb <13 g/dl in men and <12 g/dl in
      women. Cox proportional hazards models were used to assess the relative risk (RR)
      of CHD occurrence according to Hgb status, after adjusting for other risk factors
      (demographics, lipids, diabetes, hypertension, smoking, body mass index, and
      carotid intima-media thickness). A total of 13,329 participants were included.
      The interaction between Hgb concentration and serum creatinine (Scr) was
      significant (P = 0.02). Among people with anemia, a Scr >/=1.2 mg/dl in women or
      >/=1.5 mg/dl in men was associated with a higher risk of CHD (RR, 2.74; 95%
      confidence interval, 1.42 to 5.28) than those with normal Scr. In contrast, among
      those without anemia, this association was not noted (RR, 1.20; 95% confidence
      interval, 0.86 to 1.67). In conclusion, this study indicates that high Scr is
      associated with almost a threefold risk of CHD among middle-aged people with
      anemia, whereas no increased risk is found in people with high Scr in the absence
      of anemia.

PMID- 14569103
TI  - High proteinase 3-anti-neutrophil cytoplasmic antibody (ANCA) level measured by
      the capture enzyme-linked immunosorbent assay method is associated with decreased
      patient survival in ANCA-associated vasculitis with renal involvement.
AB  - Wegener granulomatosis (WG) and microscopic polyangiitis (MP), diseases
      associated with antineutrophil cytoplasmic antibodies (ANCA), had an extremely
      poor prognosis before the introduction of cyclophosphamide and corticosteroids
      for their treatment. However, there is still reduced patient survival, and some
      studies have documented severe side effects of the immunosuppressants used. This
      10-yr follow-up study assessed 117 consecutive patients with WG or MP with biopsy
      confirmed renal involvement. The cumulative relative patient survival was lower:
      0.664 for women and 0.648 for men. The causes of death (n = 64) were in most
      cases registered as associated with the vasculitic disease. Analysis of possible
      predictive factors for patient survival by multiple Cox regression analysis
      revealed that a very high level of proteinase 3 (PR3)-ANCA measured by the
      capture ELISA method, a diagnosis of MP, and older age were factors predicting
      poorer patient survival. High levels of B-thrombocytes at time of diagnosis were
      associated with a better prognosis. For patients surviving the first year,
      remission-sustaining therapy with azathioprine for longer than 12 mo was
      associated with improved patient survival. Thirty-nine patients developed end
      stage renal failure. Elevated serum creatinine at time of diagnosis and a very
      high level of PR3-ANCA by capture ELISA were factors predicting a higher risk for
      renal failure during follow-up. The epitope on PR3 assessed by capture ELISA
      needs to be further analyzed and explored: it seemed to implicate poorer patient
      and renal survival in WG or MP with renal involvement.

PMID- 14569104
TI  - Risk factors for chronic kidney disease: a prospective study of 23,534 men and
      women in Washington County, Maryland.
AB  - Chronic kidney disease (CKD) is an increasing cause of morbidity and mortality in
      the United States. Prospective data on risk factors for CKD are limited to men,
      and few studies examine the importance of smoking. The authors performed a
      community-based, prospective observational study of 20-yr duration to examine the
      association between hypertension and smoking on the future risk of CKD in 23,534
      men and women in Washington County, Maryland. CKD was identified as end-stage
      renal disease in the Health Care Financing Administration database or kidney
      disease listed on the death certificate. All cases were confirmed as CKD by
      medical chart review. Adjusted relative hazards of CKD were modeled using Cox
      proportional hazards regression including age as the time variable and baseline
      BP, cigarette smoking, gender, and diabetes status as risk factors. The adjusted
      hazard ratio (95% confidence interval) of developing CKD among women was 2.5
      (0.05 to 12.0) for normal BP, 3.0 (0.6 to 14.4) for high-normal BP, 3.8 (0.8 to
      17.2) for stage 1 hypertension, 6.3 (1.3 to 29.0) for stage 2 hypertension, and
      8.8 (1.8 to 43.0) for stages 3 or 4 hypertension compared with individuals with
      optimal BP. In men, the relationship was similar but somewhat weaker than in
      women, with corresponding hazard ratios of 1.4 (0.2 to 12.1), 3.3 (0.4 to 25.6),
      3.0 (0.4 to 22.2), 5.7 (0.8 to 43.0), and 9.7 (1.2 to 75.6), respectively.
      Current cigarette smoking was also significantly associated with risk of CKD in
      both men and women (hazard ratio in women 2.9 [1.7 to 5.0] and in men 2.4 [1.5 to
      4.0]). A large proportion of the attributable risk of CKD in this population was
      associated with stage 1 hypertension (23%) and cigarette smoking (31%). In
      conclusion, CKD risk shows strong graded relationships to the sixth report of the
      Joint National Committee (JNC-VI) on Prevention, Detection Evaluation and
      Treatment of High BP criteria for BP, to diabetes, and to current cigarette
      smoking that are at least as strong in women as in men.

PMID- 14569105
TI  - Comparison of arteriovenous grafts in the thigh and upper extremities in
      hemodialysis patients.
AB  - Placement of a thigh graft is an option in hemodialysis patients who have
      exhausted all upper extremity sites for permanent vascular access. The outcome of
      thigh grafts has been reported only in retrospective studies. The outcomes of 409
      grafts placed at a single institution during a 3.5-yr period were evaluated
      prospectively, including 63 thigh grafts (15% of the total). Information was
      recorded on surgical complications, dates of radiologic and surgical
      interventions, and date of graft failure. The technical failure rate was
      approximately twice as high for thigh grafts, as compared with upper extremity
      grafts (12.7 versus 5.8%; P = 0.046). Intervention-free survival was similar for
      thigh and upper extremity grafts (median, 3.9 versus 3.5 mo; P = 0.55).
      Thrombosis-free survival was also comparable for thigh and upper extremity grafts
      (median, 5.7 versus 5.5 mo; P = 0.94). Cumulative survival (time to permanent
      failure) was similar for thigh and upper extremity grafts (median, 14.8 versus
      20.8 mo; P = 0.62). When technical failures were excluded, the median cumulative
      survival was 27.6 mo for thigh grafts and 22.5 mo for upper extremity grafts (P =
      0.72). The frequency of angioplasty (0.28 versus 0.57 per year), thrombectomy
      (1.58 versus 0.94 per year), surgical revision (0.28 versus 0.18 per year), and
      total intervention rate (2.15 versus 1.70 per year) was similar between thigh and
      upper extremity grafts. Access loss as a result of infection tended to be higher
      for thigh grafts than for upper extremity grafts (11.1 versus 5.2%; P = 0.07). In
      conclusion, placement of thigh grafts should be considered a viable option among
      hemodialysis patients who have exhausted all options for a permanent vascular
      access in both upper extremities.

PMID- 14569106
TI  - Survival of functionally anuric patients on automated peritoneal dialysis: the
      European APD Outcome Study.
AB  - The European APD Outcome Study (EAPOS) is a 2-yr, prospective, multicenter study
      of the feasibility and clinical outcomes of automated peritoneal dialysis (APD)
      in anuric patients. A total of 177 patients were enrolled with a median age of 54
      yr (range, 21 to 91 yr). Previous median total time on dialysis was 38 mo (range,
      1.6 to 259 mo), and 36% of patients had previously been on hemodialysis for >90
      d. Diabetes and cardiovascular disease were present in 17% and 46% of patients,
      respectively. The APD prescription was adjusted at physician discretion to aim
      for creatinine clearance (Ccrea) >/=60 L/wk per 1.73 m(2) and ultrafiltration
      (UF) >/=750 ml/24 h during the first 6 mo. Baseline solute transport status (D/P)
      was determined by peritoneal equilibration test. At 1 yr, 78% and 74% achieved
      Ccrea and UF targets, respectively; median drained dialysate volume was 16.2 L/24
      h with 50% of patients using icodextrin. Baseline D/P was not related to UF
      achieved at 1 yr. At 2 yr, patient survival was 78% and technique survival was
      62%. Baseline predictors of poor survival were age (>65 yr; P = 0.006),
      nutritional status (Subjective Global Assessment grade C; P = 0.009), diabetic
      status (P = 0.008), and UF (<750 ml/24 h; P = 0.047). Time-averaged analyses
      showed that age, Subjective Global Assessment grade C and diabetic status
      predicted patient survival with UF the next most significant variable (risk
      ratio, 0.5/L per d; P = 0.097). Baseline Ccrea, time-averaged Ccrea, and baseline
      D/P had no effect on patient or technique survival. This study shows that anuric
      patients can successfully use APD. Baseline UF, not Ccrea or membrane
      permeability, is associated with patient survival.

PMID- 14569107
TI  - Gene expression profiles of podocyte-associated molecules as diagnostic markers
      in acquired proteinuric diseases.
AB  - For identifying potential diagnostic markers of proteinuric glomerulopathies,
      glomerular mRNA levels of molecules relevant for podocyte function (alpha-actinin
      4, glomerular epithelial protein 1, Wilms tumor antigen 1, synaptopodin,
      dystroglycan, nephrin, podoplanin, and podocin) were determined by quantitative
      real-time RT-PCR from microdissected glomeruli. Biopsies from 83 patients with
      acquired proteinuric diseases were analyzed (minimal change disease [MCD; n =
      13], benign nephrosclerosis [n = 16], membranous glomerulopathy [n = 31], focal
      and segmental glomerulosclerosis [FSGS; n = 9], and controls [n = 14]). Gene
      expression levels normalized to two different housekeeping transcripts
      (glyceraldehyde-3-phosphate-dehydrogenase and 18 S rRNA) did not allow a
      separation between proteinuric disease categories. However, a significant
      positive correlation between alpha-actinin-4, glomerular epithelial protein 1,
      synaptopodin, dystroglycan, Wilms tumor antigen 1, and nephrin was found in all
      analyzed glomeruli, whereas podocin mRNA expression did not correlate. Because
      varying amounts of housekeeper cDNA per glomerulus can confound expression ratios
      relevant for a subpopulation of cells, an "in silico" microdissection was
      performed using a podocyte-specific cDNA as a reference gene. Expression ratio of
      podocin to synaptopodin, the two genes with the most disparate expression,
      allowed a robust separation of FSGS from MCD and nephrosclerosis. Segregation of
      FSGS from MCD via this ratio was confirmed in an independent population of
      formaldehyde-fixed archival biopsies (MCD, n = 5; FSGS, n = 4) after glomerular
      laser capture microdissection. In addition, the expression marker was able to
      predict steroid responsiveness in diagnostically challenging cases of MCD versus
      FSGS (n = 6). As the above approach can be performed as an add-on diagnostic
      tool, these molecular diagnostic parameters could give novel information for the
      management of proteinuric diseases.

PMID- 14569108
TI  - Nomogram for predicting the likelihood of delayed graft function in adult
      cadaveric renal transplant recipients.
AB  - Delayed graft function (DGF) is the need for dialysis in the first week after
      transplantation. Studied were risk factors for DGF in adult (age >/=16 yr)
      cadaveric renal transplant recipients by means of a multivariable modeling
      procedure. Only donor and recipient factors known before transplantation were
      chosen so that the probabilities of DGF could be calculated before
      transplantation and appropriate preventative measures taken. Data on 19,706
      recipients of cadaveric allografts were obtained from the United States Renal
      Data System registry (1995 to 1998). Graft losses within the first 24 h after
      surgery were excluded from the analysis (n = 89). Patients whose DGF information
      was missing or unknown (n = 2820) and patients missing one or more candidate
      predictors (n = 2951) were also excluded. By means of a multivariable logistic
      regression analysis, factors contributing to DGF in the remaining 13,846 patients
      were identified. After validating the logistic regression model, a nomogram was
      developed as a tool for identifying patients at risk for DGF. The incidence of
      DGF was 23.7%. Sixteen independent donor or recipient risk factors were found to
      predict DGF. A nomogram quantifying the relative contribution of each risk factor
      was created. This index can be used to calculate the risk of DGF for an
      individual by adding the points associated with each risk factor. The nomogram
      provides a useful tool for developing a pretransplantation index of the
      likelihood of DGF occurrence. With this index in hand, better informed treatment
      and allocation decisions can be made.

PMID- 14569109
TI  - Preventing bone loss in renal transplant recipients with vitamin D.
AB  - Very rapid bone loss, osteopenia, and osteoporosis have been documented in the
      first 6 to 12 mo after renal transplantation. Investigated was the effect of
      treatment with active vitamin D on the prevention of posttransplantation bone
      loss. Forty adult men who were recent renal transplant recipients were enrolled
      onto the study. Patients were randomized into two groups: group 1 received daily
      alfacalcidol 0.5 micro g by mouth, and group 2 (control) received placebo. Every
      patient in both groups received daily 500-mg calcium carbonate supplements.
      Parameters of bone metabolism and bone mineral density measured at three sites
      were assessed before and after the study period. Bone mineral density was
      increased by 2.1%, 1.8%, and 3.2% at lumbar spine, femoral neck, and forearm,
      respectively, in group 1, whereas it decreased by 3.2%, 3.8%, and 1.8% at the
      same sites in the control group (P < 0.05). Serum intact parathyroid hormone
      level decreased significantly in group 1 compared with the control group (P =
      0.003). Early bone loss that occurs during the first 1 yr after renal
      transplantation could be prevented by alfacalcidol. Use of alfacalcidol early
      after transplantation is safe and well tolerated.

PMID- 14569110
TI  - Long-term graft survival with neoral and tacrolimus: a paired kidney analysis.
AB  - Calcineurin inhibitors (CNI) are an important component of most immunosuppressive
      protocols utilized in renal transplantation. Both CNI available (cyclosporine and
      tacrolimus) have been used for many years. Studies comparing the efficacy of
      these two agents in terms of long-term graft or patient survival have thus far
      failed to show an advantage for either agent. This failure to show a difference
      could possibly be due to underpowering of clinical trials. The authors used the
      SRTR database to analyze 5-yr graft survival of the microemulsion formulation of
      cyclosporine (Neoral) as compared with tacrolimus. To minimize the donor
      variability and bias, a paired kidney analysis was used. Deceased donors from the
      years 1995-2002 were analyzed from the SRTR database. All paired kidneys during
      this period, where one kidney was allocated to a patient receiving initial Neoral
      therapy and its mate allocated to a patient receiving initial tacrolimus therapy
      were evaluated. Multivariate and univariate analysis were performed. Univariate
      analysis demonstrated equivalent graft survival for Neoral compared with
      tacrolimus (66.9% versus 65.9%, respectively). Multivariate analysis could not
      demonstrate a difference in risk for 5-yr patient survival or graft loss. Renal
      function was superior for tacrolimus at all time points, whereas the slope of
      1/Cr over time did not differ for the two agents. In this paired kidney analysis,
      no difference in 5-yr renal allograft survival could be found between the two
      agents. Renal function was superior in the patients receiving initial tacrolimus
      therapy; however, slope of 1/Cr did not differ between the agents.

PMID- 14569111
TI  - Angiotensin II and oxidative stress: an unholy alliance.

PMID- 14569112
TI  - Tolerance and autoimmunity in anti-GBM disease.

PMID- 14569113
TI  - Regression lines in chronic kidney disease.

PMID- 14569115
TI  - In vivo reversion to normal of inherited mutations in humans.
AB  - There are increasing reports of multiple different types of somatic mosaicism
      detected in patients with inherited and non-inherited disorders. The
      characteristics of several of the major types of mosaicism will be outlined, and
      contrasted with somatic mosaicism, which is the focus of this article. This
      review examines examples of somatic mosaicism due to differences in DNA sequence
      arising from in vivo site specific reversion to normal of inherited mutations in
      humans. While several known mechanisms of reversion are evident in a number of
      these examples, they are not in some others. The possible significance of the
      role of selection, particularly in view of recent results of gene therapy, is
      discussed.

PMID- 14569116
TI  - Mapping of a new locus for autosomal recessive non-syndromic mental retardation
      in the chromosomal region 19p13.12-p13.2: further genetic heterogeneity.
AB  - OBJECTIVE: To identify and clinically evaluate four consanguineous families of
      Israeli Arab origin with non-syndromic mental retardation (NSMR), comprising a
      total of 10 affected and 24 unaffected individuals. PARTICIPANTS AND METHODS: All
      the families originated from the same small village and had the same family name.
      Association of the condition in these families with the two known autosomal
      recessive NSMR loci on chromosomes 3p25-pter and 4q24 (neurotrypsin gene) was
      excluded. RESULTS: Linkage of the disease gene to chromosome 19p13.12-p13.2(Zmax
      = 7.06 at theta = 0.00) for the marker D19S840 was established. All the affected
      individuals were found to be homozygous for a common haplotype for the markers
      cen-RFX1-D19S840-D19S558-D19S221-tel. CONCLUSIONS: The results suggest that the
      disease is caused by a single mutation derived from a single ancestral founder in
      all the families. Recombination events and a common disease bearing haplotype
      defined a critical region of 2.4 Mb, between the loci D19S547 proximally and
      D19S1165 distally.

PMID- 14569117
TI  - Disruption of a novel member of a sodium/hydrogen exchanger family and DOCK3 is
      associated with an attention deficit hyperactivity disorder-like phenotype.
AB  - BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a complex
      condition with high heritability. However, both biochemical investigations and
      association and linkage studies have failed to define fully the underlying
      genetic factors associated with ADHD. We have identified a family co-segregating
      an early onset behavioural/developmental condition, with features of ADHD and
      intellectual disability, with a pericentric inversion of chromosome 3, 46N
      inv(3)(p14:q21). METHODS: We hypothesised that the inversion breakpoints affect a
      gene or genes that cause the observed phenotype. Large genomic clones (P1
      derived/yeast/bacterial artificial chromosomes) were assembled into contigs
      across the two inversion breakpoints using molecular and bioinformatic
      technologies. Restriction fragments crossing the junctions were identified by
      Southern analysis and these fragments were amplified using inverse PCR. RESULTS:
      The amplification products were subsequently sequenced to reveal that the
      breakpoints lay within an intron of the dedicator of cytokinesis 3 (DOCK3) gene
      at the p arm breakpoint, and an intron of a novel member of the solute carrier
      family 9 (sodium/hydrogen exchanger) isoform 9 (SLC9A9) at the q arm. Both genes
      are expressed in the brain, but neither of the genes has previously been
      implicated in developmental or behavioural disorders. CONCLUSION: These two
      disrupted genes are candidates for involvement in the pathway leading to the
      neuropsychological condition in this family.

PMID- 14569121
TI  - Homozygosity mapping of a gene for arterial tortuosity syndrome to chromosome
      20q13.
AB  - BACKGROUND: Arterial tortuosity syndrome (ATS) is an uncommon connective tissue
      disorder of unknown aetiology. The most prominent feature is tortuosity of the
      large arteries, but lengthening, stenosis, and aneurysm formation are also
      frequent. METHODS: We performed a genomewide screen by homozygosity mapping of
      three consanguineous multiplex families, two from Morocco, and one from Italy,
      which included 11 ATS patients. The two families from Morocco may possibly have a
      common ancestor. RESULTS: We mapped the ATS gene to chromosome 20q13.
      Recombinations within an extended haplotype of 11 microsatellite markers
      localised the ATS gene between markers D20S836 and D20S109, an interval of 9.5
      cM. CONCLUSIONS: Cloning and completing functional and structural analysis of the
      ATS gene may provide new insights into the molecular mechanisms of elastogenesis.

PMID- 14569122
TI  - A tRNA(Ala) mutation causing mitochondrial myopathy clinically resembling
      myotonic dystrophy.

PMID- 14569119
TI  - Genetic changes in the RNA components of RNase MRP and RNase P in Schmid
      metaphyseal chondrodysplasia.
AB  - BACKGROUND: The Schmid type of metaphyseal chondrodysplasia (MCDS) is generally
      due to mutations in COL10A1 encoding for type X collagen of cartilage. METHODS:
      We performed a study on the genes coding for the RNA components of RNase MRP
      (MRPR) and RNase P (H1RNA) among 20 patients with diagnosis of MCDS and no
      mutations in COL10A1. RESULTS: Two patients were found to be homozygous for a
      base substitution G for A at nucleotide 70 of RMRP, which is the major mutation
      causing cartilage-hair hypoplasia. No pathogenic mutations were detected in
      H1RNA. CONCLUSION: Cartilage-hair hypoplasia diagnosis should be considered in
      patients with metaphyseal chondrodysplasia even in the absence of any extra
      skeletal manifestations if no mutation in COL10A1 can be found and the family
      history is compatible with autosomal recessive inheritance. Correct diagnosis is
      important for genetic counselling and for proper follow up of the patients.

PMID- 14569124
TI  - Genotype-phenotype correlations for cataracts in neurofibromatosis 2.

PMID- 14569125
TI  - Short-limbed dwarfism with bowing, combined immune deficiency, and late onset
      aplastic anaemia caused by novel mutations in the RMPR gene.

PMID- 14569127
TI  - Effect of the peroxisome proliferator activated receptor-gamma gene Pro12Ala
      variant on body mass index: a meta-analysis.

PMID- 14569126
TI  - Genetic homogeneity and phenotypic variability among Ashkenazi Jews with Usher
      syndrome type III.

PMID- 14569129
TI  - Receptor mediated effect of serotonergic transmission in patients with bipolar
      affective disorder.

PMID- 14569130
TI  - A twofold increase in BRCA mutation related prostate cancer among Ashkenazi
      Israelis is not associated with distinctive histopathology.

PMID- 14569132
TI  - Evaluation of genotype-phenotype correlations in neurofibromatosis type 1.

PMID- 14569133
TI  - CHEK2 1100delC and colorectal cancer.

PMID- 14569134
TI  - PTEN hamartoma tumour syndrome: variability of an entity.

PMID- 14569135
TI  - Prader-Willi syndrome: the psychopathological phenotype in uniparental disomy.

PMID- 14569136
TI  - An alternative to FISH: detecting deletion and duplication carriers within 24
      hours.

PMID- 14569137
TI  - The effect of sequence variations within the coding region of the C1 inhibitor
      gene on disease expression and protein function in families with hereditary angio
      oedema.

PMID- 14569138
TI  - A synonymous codon change in the LMNA gene alters mRNA splicing and causes limb
      girdle muscular dystrophy type 1B.

PMID- 14569139
TI  - Heterogeneity of breakpoints in non-LCR-mediated large constitutional deletions
      of the 17q11.2 NF1 tumour suppressor region.

PMID- 14569141
TI  - Comparative aspects of intracellular proteolytic processing of peptide hormone
      precursors: studies of proopiomelanocortin processing.
AB  - In this review, the mechanisms underlying the intracellular processing of peptide
      hormone precursors, with a focus on proopiomelanocortin (POMC), were discussed on
      the basis of recent information. POMC as well as other prohormones is processed
      to active peptides through proteolytic cleavage by prohormone convertases PC1
      and/or PC2. However, the cleavage-specificity of PC1 and PC2 in mammals is
      somewhat different from that in amphibians. From the comparative endocrinological
      point of view, expression and tissue distribution of PC1 and PC2 were discussed
      here. In mammals, proteolytic processing of POMC occurs coordinately with the
      maturation of secretory granules. Studies using immunoelectron microscopy with
      DAMP (3-[2,4-dinitroanilino]-3'-amino-N-methyldipropylamine) as a pH probe
      revealed that the acidic pH in the secretory granules, generated by vacular type
      H+-ATPase, provides a favorable environment for activating PC1 in AtT-20 cells, a
      mouse corticotrope tumor cell line. Recent data indicate that the 7B2 protein
      serves as a chaperone in the regulation of PC2 activation and to control the
      timing for activating the convertase. Together, secretory granules in endocrine
      and neuroendocrine cells provide proper sites for biosynthesizing hormones in
      addition to serving as storage sites and vehicles for the transport of peptide
      hormones.

PMID- 14569140
TI  - BRCA1 c.2845insA is a recurring mutation with a founder effect in Singapore Malay
      women with early onset breast/ovarian cancer.

PMID- 14569142
TI  - Juvenile hormone biosynthesis in diapause and nondiapause females of the adult
      blow fly Protophormia terraenovae.
AB  - In vitro synthetic activities of juvenile hormones (JH) were examined using a
      radiochemical assay in diapause females and reproductive females of the blow fly,
      Protophormia terraenovae. Thin layer chromatography showed that products of the
      corpus allatum (CA) comigrated with a synthetic sample of JH III bisepoxide but
      neither with JH III nor methylfarnesoate. JH synthetic activities increased in
      females reared under LD 18:6 at 25 degrees C, as the ovaries developed. The
      synthetic activities remained low in previtellogenic females reared under LD
      12:12 at 20 degrees C. Removal of the pars intercerebralis completely prevented
      ovaries from development under reproductive conditions, and removal of the pars
      lateralis caused partial or full development of ovaries under diapause-inducing
      conditions. In these operated animals, the JH synthetic activities were not
      significantly different from those of the intact and sham-operated animals. The
      results indicate that the CA in P. terraenovae produces mainly JH III bisepoxide
      and a decrease in the JH production rate is a cause of diapause induction. PI
      neurons and PL neurons in the brain do not directly mediate changes in the JH
      production rate, but regulate ovarian development cooperatively with some unknown
      allatostatic and allatotropic factors.

PMID- 14569143
TI  - Presence and characterization of complement-like activity in the amphioxus
      Branchiostoma belcheri tsingtauense.
AB  - The humoral fluid of Branchiostoma belcheri tsingtauense was examined for the
      presence of complement-like activity. The humoral fluid showed hemolytic activity
      for rabbit erythrocytes and those from species representing mammals, birds,
      amphibians and fish, but not sensitized sheep erythrocytes. There was no
      relationship between phylogeny of the target erythrocytes and degree of
      hemolysis. The hemolytic activity was optimally assayed at 20 degrees C, at pH
      7.5, and in the presence of 10 mM Mg2+. The hemolytic activity was Mg2+-dependent
      and heat-sensitive, and was abrogated by treatment with rabbit anti-human C3
      serum, zymosan, methylamine, hydrazine, and phenylmethylenesulfonyl fluoride. In
      addition, Western blotting and titration by turbidimetric immunoassay (TIA)
      revealed that amphioxus humoral fluid contained C3 component, and its
      concentration is about 1.17 mg/ml, which is comparable to C3 concentration in
      human or dog sera. These suggest that the hemolytic activities displayed by
      amphioxus humoral fluid appear to represent the vertebrate complement system
      probably operating via the alternative pathway.

PMID- 14569144
TI  - Comparative studies on the internal defense system of schistosome-resistant and 
      susceptible amphibious snail Oncomelania nosophora 1. Comparative morphological
      and functional studies on hemocytes from both snails.
AB  - Two morphologically distinct blood cell types (hemocytes), Type I and Type II
      were found coexisting in hemolymph from two kinds of snails, Oncomelania
      nosophora strain, viz. from the Nirasaki strain (schistosome-resistant snail) and
      the Kisarazu strain (schistosome-susceptible snail). Ten min after inoculation of
      SRBC, the majority of Type I cells from Nirasaki strain flattened and spread over
      the surface of the glass plate by extending pseudopodia. In the Kisarazu strain,
      Type I cells adhered to the surface of substrate with spike-like filopodia, but
      did not form spreading lamellipodia. Type I cell from the Nirasaki strain
      phagocytosed SRBC but that from the Kisarazu strain did not. The starting time of
      recognition of foreign materials was slightly different in the Type I hemocytes
      from the two strains. Type II cells from both strains were round and lymphocyte
      like. Ten or sixty min after incubation, Type II cells from neither strain
      adhered to the surface of substrate or SRBC, and did not phagocytose SRBC. Type
      II cells from the Nirasaki strain were quite similar to those from the Kisarazu
      strain. We concluded that Type I cells from the schistosome-resistant snail,
      Nirasaki strain, possessed higher phagocytic activity than those from the
      susceptible snail, Kisarazu strain, despite the morphological similarities of the
      hemocytes from both strains.

PMID- 14569145
TI  - Construction of a cDNA microarray derived from the ascidian Ciona intestinalis.
AB  - A cDNA microarray was constructed from a basal chordate, the ascidian Ciona
      intestinalis. The draft genome of Ciona has been read and inferred to contain
      approximately 16,000 protein-coding genes, and cDNAs for transcripts of 13,464
      genes have been characterized and compiled as the "Ciona intestinalis Gene
      Collection Release I". In the present study, we constructed a cDNA microarray of
      these 13,464 Ciona genes. A preliminary experiment with Cy3- and Cy5-labeled
      probes showed extensive differential gene expression between fertilized eggs and
      larvae. In addition, there was a good correlation between results obtained by the
      present microarray analysis and those from previous EST analyses. This first
      microarray of a large collection of Ciona intestinalis cDNA clones should
      facilitate the analysis of global gene expression and gene networks during the
      embryogenesis of basal chordates.

PMID- 14569146
TI  - Sex differentiation and pubertal development of gonads in the viviparous
      mosquitofish, Gambusia affinis.
AB  - The ontogenetic development of gonads from embryo to adult was observed
      histologically in the viviparous teleost, Gambusia affinis. Primordial germ cells
      (PGCs) appeared in the subendodermal space of the embryo 14 days before birth,
      and then transferred to the dorsal mesentery to form paired genital ridges 12
      days before birth. The PGCs proliferated in the genital ridge, forming gonadal
      primordia 10 days before birth. All gonadal primordia differentiated to the ovary
      containing oocytes 2 days before birth, but then redifferentiated to the ovary
      and testis just after birth. This indicates that the mosquitofish is a juvenile
      hermaphroditic species. The characteristics of gonadal sex differentiation just
      after birth were enlargement of the oocytes in females, and invasion of somatic
      cells from the hilar region to an inner portion of the gonad in males. The paired
      ovary fused at the basal area 5 days after birth, then on the ventral and dorsal
      portions, developing into a single ovary 10 days after birth. During this time a
      single ovarian cavity was formed on the dorsal portion of the ovary. The paired
      testes fused only at the basal area and became a single testis having two main
      lobes 10 days after birth. The oocytes gradually developed and began
      vitellogenesis 100 days after birth, but did not reach maturation until 110 days
      after birth. Spermatogenic cells formed cysts at 20 days, began meiosis at 70
      days, and matured to form sperm balls 90 days after birth. The male fish sexually
      matured earlier than the female.

PMID- 14569147
TI  - Phylogenetic position of a deep-sea ascidian, Megalodicopia hians, inferred from
      the molecular data.
AB  - Ascidians inhabit both shallow water and the deep sea. The phylogenetic position
      of deep-sea ascidians has not been sufficiently investigated because of their
      unusual habitats. The family Octacnemidae is one such enigmatic deep-sea
      ascidian. In this report, we determined the sequences of the 18SrDNA and a
      mitochondrial protein gene of Megalodicopia hians belonging to the family
      Octacnemidae, and we analyzed its phylogenetic relationship with other ascidians.
      A phylogenetic relationship of this family with the families Cionidae and/or
      Corellidae has been suspected based on a small number of morphological
      characteristics. However, our results suggested that M. hians has a close
      relationship to the family Corellidae and might originate from them. This is the
      first report of the molecular phylogenetic analysis of a deep-sea ascidian.

PMID- 14569148
TI  - A description of the second species of the family Dipteromimidae (Insecta,
      Ephemeroptera), and genetic relationship of two dipteromimid mayflies inferred
      from mitochondrial 16S rRNA gene sequences.
AB  - A new mayfly species, Dipteromimus flavipterus sp. nov., of the family
      Dipteromimidae is described on the basis of specimens of males, females and
      mature nymphs collected from Ofunato, Iwate Prefecture, Japan. This new
      Dipteromimus species is characterized by a large body size, a yellowish body
      color (especially the frontal border of the forewings), short penis lobes, a
      slight elongation backwards of the female 7th abdominal sternum, and a rounded
      backward projection of the female 9th abdominal sternum, etc., in comparison with
      another known dipteromimid mayfly Dipteromimus tipuliformis McLachlan, 1875. Full
      descriptions of males, females, mature nymphs and eggs of this new species have
      been provided. We also examined and discussed the genetic relationship of two
      dipteromimid mayflies to settle the taxonomic status, inferred from the partially
      sequenced large mitochondrial ribosomal subunit (16S rRNA) genes. Consequently,
      phenetic and molecular phylogenetic analyses agreed in terms of clustering.

PMID- 14569149
TI  - Javanese species of the mite genus Macrocheles (Arachnida: Acari: Gamasina:
      Macrochelidae).
AB  - Twelve mite species of the genus Macrocheles (Acari: Macrochelidae) were
      collected from the body surface of dung beetles in Java, Indonesia. Of these,
      three species, i.e., Macrocheles jabarensis, M. jonggolensis, and M.
      sukabumiensis, were described as new to science. Female of M. dispar was
      redescribed. Two species, i.e., M. baliensis and M. sukaramiensis, were recorded
      from Java for the first time. The occurrence of five species previously recorded
      from Java, i.e., M. hallidayi, M. kraepelini, M. limue, M. oigru, and M.
      merdarius, were reconfirmed. Taxonomic status of M. sp. aff. glaber was not
      settled in the present study, because we could not obtain the male and immatures
      which are indispensable for exact identification. In total 15 species of the
      genus Macrocheles, including 3 species already recorded but not collected in this
      research (M. crispa, M. krantzi, and M. subbadius), are known from Java up to
      date.

PMID- 14569150
TI  - A remarkable new species of Stephensia Stainton (Insecta: Lepidoptera:
      Elachistidae) from Belize rainforest (Central America).
AB  - Stephensia armata sp. n., a remarkable species is described from Belize (Central
      America). The external features and genitalia of the male are figured and
      described in detail. A distribution map for all six Elachistidae species,
      currently recorded from tropical America, is given: Perittia smaragdophanes
      (Meyrick), P. punatensis Kaila, Elachista albisquamella Zeller, E. saccharella
      (Busck), E. vasrana Kaila and Stephensia armata Sruoga, sp. n.

PMID- 14569151
TI  - Geographic variation and diversity of the cytochrome b gene in Japanese wild
      populations of medaka, Oryzias latipes.
AB  - We conducted a polymerase chain reaction--restriction fragment length
      polymorphism (PCR-RFLP) analysis of the mitochondrial cytochrome b gene to
      elucidate the detailed genetic population structure of Japanese wild populations
      of medaka, Oryzias latipes. The analysis of 1,225 specimens collected from 303
      sites identified 67 mitotypes. Subsequently we determined the nucleotide
      sequences of the complete cytochrome b gene (1141-bp) to clarify the phylogenetic
      relationships among mitotypes. The phylogenetic tree based on nucleotide
      sequences indicated three major clades (A, B and C) that differed by 11.3-11.8%,
      corresponding to three clusters previously identified by RFLP analysis of entire
      mitochondrial DNAs. The geographic distribution of mitotypes in clades A and B
      was fully concordant with the Northern and Southern Populations defined by
      allozymes. Clade A could be subdivided into three subclades and clade B into
      eleven, with sequence divergences among subclades of 1.3-5.8%. Each distribution
      of mitotypes in subclades roughly corresponded to that of mtDNA haplotypes in
      subclusters previously identified. Mitotypes in clade C were found only in the
      Kanto district. The phylogenetic relationships and the estimated divergence times
      suggest that three Japanese clades originated from a common ancestor and were
      separated during the Pliocene, and that the regional differentiation of subclades
      was closely connected with the geological history of the Quaternary. This study
      has also demonstrated the possibility of artificial disturbance of natural
      distribution especially in the Kanto district and the superior efficacy of PCR
      RFLP analysis as a simple method for detecting genetic variation and artificial
      gene flow of medaka.

PMID- 14569152
TI  - Genomic structure and expression of the soluble guanylyl cyclase alpha2 subunit
      gene in the medaka fish Oryzias latipes.
AB  - A cDNA clone encoding the soluble guanylyl cyclase alpha2 subunit was isolated
      from medaka fish (Oryzias latipes) and designated as OlGCS-alpha2. The OlGCS
      alpha2 cDNA was 3,192 bp in length and the open reading frame (ORF) encodes a
      protein of 805 amino acids. The deduced amino acid sequence has high similarity
      to that of the mammalian alpha2 subunit gene except for the N-terminal regulatory
      domain. The C-terminal 5 amino acids, "RETSL", which have been reported to
      interact with the post synaptic density protein (PSD)-95 were conserved. An RNase
      protection assay with adult fish organs showed that OlGCS-alpha2 was expressed
      mainly in the brain and testis. The complete nucleotide sequence (about 41 kbp)
      of the OlGCS-alpha2 genomic DNA clone isolated from a medaka fish BAC library
      indicated that the OlGCS-alpha2 gene consisted of 9 exons and 8 introns. The 5'
      flanking region and larger introns, such as introns 1, 4, and 7, contained the
      several fragments conserved in the nucleotide sequences of Rex6 (non-long
      terminal repeat retrotransposon), MHC class I genomic region, and OlGC1, the
      medaka fish homolog of the mammalian guanylyl cyclase B gene. Linkage analysis on
      the medaka fish chromosome demonstrated that the OlGCS-alpha2 gene was mapped to
      LG13; this mapping position was different from those for the OlGCS-alpha1 and
      OlGCS-beta1 genes (LG1).

PMID- 14569153
TI  - Intra- and interspecific genetic complexities of two Eothenomys species in
      Honshu, Japan.
AB  - Differences in the nuclear ribosomal DNA (rDNA), mitochondrial DNA (mtDNA),
      cytochrome b (Cytb), and Y chromosomal Sry genes were used to assess intra- and
      interspecific relationships in two Japanese red-backed voles, Eothenomys
      andersoni and E. smithii, focusing on areas where the two species might come into
      contact. In the Kii Peninsula, southwestern Honshu, which contains an allopatric
      population of E. andersoni isolated from its main range, the rDNA-RFLP data
      provide robust evidence of past mutual interspecific gene introgression, while
      the Cytb and Sry sequences were specific to this population. In central Honshu,
      where E. andersoni and E. smithii inhabit higher and lower altitudes,
      respectively, with a narrow sympatric zone, the rDNA-RFLP and Sry variation was
      specific for each species, while introgression of the mtDNA from E. smithii to E.
      andersoni was seen. These complex patterns in the gene markers are consistent
      with our previous notions derived from sex chromosome variation. Our previous and
      present data strongly suggest that the evolution of these vole species, which are
      morphologically and cytogenetically distinct, involves complex genetic
      interactions and the resultant combinations of genes are sometimes peculiar,
      mainly due to the Cytb haplotypes. However, phylogenetic analysis using a
      combination of maternal, paternal, and biparental markers has proven useful for
      understanding the evolutionary history given the complex phylogenetic background.

PMID- 14569154
TI  - Paeonocanthus antarcticensis (Hewitt, 1965): a rare copepod parasite of
      bathypelagic fish, Bathylagus antarcticus Gunther, from the Antarctic Ocean.
AB  - Paeonocanthus antarcticensis (Hewitt, 1965) is redescribed based on four
      specimens recovered from a deep-sea smelt, Bathylagus antarcticus Gunther,
      collected in the Antarctic Ocean (65 degrees S, 139 degrees 59.6'E). Studies on
      the morphological variations of these four specimens plus comparison with the
      three documented specimens yielded that the sphyriid reported as P.
      antarcticensis from the goiter blacksmelt, Bathylagus euryops Goode & Bean, taken
      in the Northwest Atlantic Ocean is a different species. It is renamed
      Paeonocanthus hogansi n. sp.

PMID- 14569155
TI  - [Basic arrhythmogenic mechanisms in both inherited and acquired long QT
      syndrome].
AB  - The heterologous expression system will provide clues for understanding the basic
      mechanism of arrhythmogenicity in both inherited and acquired long QT syndrome,
      which are reviewed here, with emphasis on the K+ channels. Endothelin is
      implicated in the morphological and electrical remodeling of cardiac muscles in
      heart failure. The effects of endothelin on the transient outward K+ currents
      (Ito) were compared between Kv1.4 (rich in endocardial muscle) and Kv4.3 (rich in
      epicardial muscle) channels in the Xenopus oocytes expression system. Both Itos
      were decreased by stimulation of endothelin receptor ETA coexpressed with the K+
      channels. Ito of Kv1.4 was decreased by about 85% after 10(-8) M ET-1, whereas
      that of Kv4.3 was decreased by about 60%. By mutagenesis experiments, we
      identified two phosphorylation sites of PKC and CaMKII in Kv1.4 responsible for
      the decrease in Ito by ET-1. In Kv4.3 we identified a PKC phosphorylation site
      that is partly responsible for the decrease. Differences in the suppression of
      Ito could be due to the differences in intracellular signaling including the
      number of phosphorylation sites. These findings show some of the molecular
      mechanisms of ventricular arrhythmias in heart failure, resulting in dispersion
      and prolongation of action potential which elicit reentry and after
      depolarization.

PMID- 14569156
TI  - [Various functions of ClC-type Cl- channels].
AB  - Cellular functions of Cl- channels are poorly understood, in contrast to well
      established roles of cation channels. Recently, important achievements in Cl-
      channel research have been sequentially reported, including cloning of many Cl-
      channel cDNAs, linkage of gene abnormalities to human inherited disorders,
      analysis of knock-out mouse phenotype, analysis of crystal structure, and
      regulation by protein-protein interaction. Intracellular membrane Cl- channels
      are important for acidification of intracellular vesicles: ClC-5 functions for re
      absorption of low-molecular-weight proteins in renal proximal tubule, and ClC-7
      for absorption of bone matrix by osteoclasts. Abnormal functions of these
      channels result in Dent's disease characterized by proteinuria and kidney stones
      and by osteopetrosis, respectively. Plasma membrane Cl- channels, ClC-K1, ClC-K2,
      and ClC-3B, are expressed predominantly in epithelial cells and are important for
      uni-directional Cl- transport across the epithelia. Abnormalities of these
      channels are also related to human diseases: abnormal ClC-K1 to diabetes
      insipidus and abnormal ClC-K2 to Bartter's syndrome.

PMID- 14569157
TI  - [Pathophysiological roles of the prostanoids in the cardiovascular system:
      studies using mice deficient in prostanoid receptors].
AB  - Prostanoids, consisting of the prostaglandins (PGs) and thromboxanes (TXs), exert
      various actions through activation of their specific receptors. They include the
      DP, EP, FP, IP, and TP receptors for PGD2, PGE2, PGF2alpha, PGI2, and TXA2,
      respectively. Moreover, EP receptors are classified into four subtypes, the EP1,
      EP2, EP3 and EP4 receptors. Using mice lacking prostanoid receptors, we intended
      to clarify in vivo roles of prostanoids under pathophysiological conditions of
      the cardiovascular system, which include ischemia-induced cardiac injury,
      pressure overload-induced cardiac hypertrophy, renovascular hypertension,
      tachycardia during systemic inflammation and thromboembolism. The results
      demonstrated that 1) PGI2 plays an important role in attenuating the ischemic
      injury and the pressure overload-induced hypertrophy of the hearts, and also
      contributes to the development of renovascular hypertension; 2) PGE2 plays a
      cardioprotective role against the ischemic injury via both the EP3 and EP4, and
      also participates in acute thromboembolism via the EP3; and 3) both PGF2alpha and
      TXA2, which have been produced during systemic inflammation, are responsible for
      tachycardia.

PMID- 14569158
TI  - [Roles of histamine receptors in pain perception: a study using receptors gene
      knockout mice].
AB  - To study the participation of histamine H1- and H2-receptors in pain perception,
      H1 and H2 receptor knockout (KO) mice were examined for pain threshold by means
      of three kinds of nociceptive tasks. These included assays for thermal,
      mechanical, and chemical nociception. H1KO mice showed significantly fewer
      nociceptive responses to the hot-plate, tail-flick, tail-pressure, paw
      withdrawal, formalin, capsaicin, and abdominal constriction tests. Sensitivity to
      noxious stimuli in H1KO mice was significantly decreased when compared to wild
      type mice. The antinociceptive phenotypes of H2KO were relatively less prominent
      when compared to H1KO mice. We also examined the antinociceptive effects of
      intrathecally-, intracerebroventricularly-, and subcutaneously-administered
      morphine in H1KO and H2KO mice. In these nociceptive assays, the antinociceptive
      effects produced by morphine were more enhanced in both H1KO and H2KO mice. The
      effects of histamine H1- and H2-receptor antagonists on morphine-induced
      antinociception were studied in ICR mice. The intrathecal,
      intracerebroventricular and subcutaneous co-administrations of d-chlorpheniramine
      enhanced the effects of morphine in all nociceptive assays examined. In addition,
      intrathecal co-administrations of cimetidine enhanced the antinociception of
      morphine in the hot plate tests. These results suggest that existing H1 and H2
      receptors play an inhibitory role in morphine-induced antinociception in the
      spinal and supra-spinal levels.

PMID- 14569159
TI  - [Pharmacological education under the Medical Education Model Core Curriculum].
AB  - The objectives of undergraduate medical education have been shifted drastically
      during the last decades. As the world standard, basic medical knowledge, skill,
      and attitude to practice patient-centered medical care became main objectives in
      undergraduate medical education. In response to these changes in the environment
      of medical practice and education, the Medical Education Model Core Curriculum
      (MEMCC), was published in 2001. MEMCC describes general and specific behavioral
      objectives in an integrated form to be used in the practice of medicine. The
      achievement of MEMCC will be evaluated by the Nationwide Common Achievement Test.
      The test examines knowledge, skill, and attitude that is required for clinical
      clerkship. Pharmacological teachers in medical schools should discuss, study, and
      evaluate MEMCC based on their experience in the use of the curriculum. MEMCC and
      the Nationwide Common Achievement Test will enhance intra- and inter
      disciplinary, as well as inter-institutional informational exchange in the
      context and strategies in pharmacological education.

PMID- 14569160
TI  - Teaching Pharmacology in 2010--new knowledge, new tools, new attitudes.
AB  - Changes in pharmacology teaching are being driven by various pressures. These
      originate: from changes in the discipline itself; from government; from
      professional bodies; from students; from changes in teaching styles and
      opportunities; from academic staff; from ethical/animal rights considerations;
      from employers and from higher education institutions. These changes will require
      an alteration in the knowledge, skills and attitudes of academic pharmacologists
      as much as they will require changes in the way teaching is delivered and
      learning is facilitated. Pharmacology courses will be provided in a changed
      environment and must prepare students to work in a changed discipline as well as
      being appropriate for students who will take employment in non-pharmacology
      areas. Change is likely to centre around the curriculum, problem based learning,
      simulated practicals, peer assessment, use of the internet, information
      technology and interactive computer based learning, virtual learning environments
      and integrated medical courses. The most effective strategy to achieve the
      necessary changes is likely to involve collaboration between pharmacology
      teachers on a global scale and a general consciousness among current academic
      pharmacologists that we need to ensure tomorrow's academics are well prepared for
      the changed environment in which they will have to work.

PMID- 14569161
TI  - [Lipid rafts and their analytical methods].
AB  - Microdomains in cell membranes consist of caveolae and lipid rafts, in which
      cholesterol, glycolipids, and sphingomyelin are concentrated. While caveolae are
      relatively stable because caveolin, an integral protein, supports the structure,
      lipid rafts are unstable, being dynamically produced and degraded. In lipid
      rafts, flotillin is assumed to be one of the specifically located proteins. Since
      microdomains contain several signaling molecules, such as transmembrane
      receptors, they have an important role in receptor-medicated signal transduction.
      Caveolae or lipid rafts are known to be resistant to non-ionic detergents, such
      as Triton X-100. Because of this property, they are separated as the detergent
      resistant membranes when the Triton X-100-treated cell lysate is subjected to
      sucrose gradient centrifugation. On the other hand, cholesterol is an essential
      molecule to maintain microdomain structure. When the cells are treated with
      cholesterol removing agents, such as methyl-beta-cyclodextrin and filipin, the
      microdomain in cell membranes is disrupted. Thus, the cholesterol removing agents
      are utilized to determine whether the microdomain is involved in certain
      cellular/physiological responses. Recently, green fluorescent protein-tagged
      protein is used to analyze the localization of the protein in lipid rafts in
      intact cells. Research on lipid rafts will be helpful for understanding the
      detailed mechanism of signal transduction and to clarify the molecular basis of
      several diseases.

PMID- 14569162
TI  - [In vivo functional analysis of the neuropeptide PACAP using gene-targeted mice].
AB  - Mutant strains of mice with precise genetic mutations generated by gene-targeting
      technology have proved to be useful tools for linking specific genes with
      biological processes in vivo and serve as models for human diseases. Pituitary
      adenylate cyclase-activating polypeptide (PACAP) is a highly conserved
      neuropeptide that is widely expressed in the mammalian brain, and it has been
      implicated in a broad variety of physiological and pathophysiological processes.
      To assess the function of PACAP in vivo, recently, we have generated PAC1
      receptor- and PACAP-targeted mice and transgenic mice overexpressing PACAP in the
      pancreatic beta-cells. The phenotypes of these mutant mice revealed both expected
      and unexpected roles of PACAP in the brain and pancreatic functions. A
      significant contribution of genetic background as well as environmental factors
      to the knockout phenotypes was also observed. In this article, we briefly
      describe the technique of gene targeting and discuss how this method was used to
      generate PACAP and its receptor deficient mice. We also analyze how these mutants
      can contribute to our understanding of the molecular mechanism underlying higher
      nervous functions.

PMID- 14569163
TI  - [The dissociation of paratracheal ganglion neurons and its application to
      neuropharmacology].
AB  - It is generally considered that dominant excitatory control of the airway is
      exerted by the parasympathetic nervous system. In the lower airway, there are a
      number of parasympathetic ganglia on the serosal surface of the dorsal tracheal
      wall. The dissociation of these paratracheal ganglion neurons facilitates the
      ability to visualize and patch-clamp single-neurons and to control the
      surrounding solutions. This article describes technical procedures to obtain the
      single paratracheal neurons and its application to neuropharmacology. The single
      paratracheal neurons can be isolated with adherent functional synaptic terminals
      using a weak enzyme treatment. This will allow investigations of the mechanisms
      and modulation of neurotransmitter release from vagal preganglionic nerve
      terminals with unprecedented ease and accuracy.

PMID- 14569164
TI  - [Pharmacological and clinical trial data on a novel phosphate-binding polymer
      (sevelamer hydrochloride), a medicine for hyperphosphatemia in hemodialysis
      patients].
AB  - Hyperphosphatemia is one of the major complications of hemodialysis patients and
      plays a key role in the pathogenesis of cardiovascular calcification and
      secondary hyperparathyroidism. Dietary phosphate restriction and removal of
      phosphate by dialysis are insufficient to control hyperphosphatemia. Therefore,
      almost all patients undergoing hemodialysis should take oral phosphate binders.
      Sevelamer hydrochloride (sevelamer) is a novel phosphate-binding polymer that
      contains neither aluminum nor calcium, and it is not absorbed from the
      gastrointestinal tract. In rat models with progressive chronic renal
      insufficiency, in addition to lowering effects on serum levels of phosphorus,
      calcium x phosphorus product, and parathyroid hormone, dietary treatment of
      sevelamer can prevent parathyroid hyperplasia, vascular calcification, high
      turnover bone lesion, and renal functional deterioration. In clinical studies
      with hemodialysis patients, sevelamer lowers serum phosphorus and calcium x
      phosphorus product without any incidence of hypercalcemia. Switching calcium
      containing phosphate binders to sevelamer can decrease the percentage of
      hypoparathyroidism and hyperparathyroidism by negative calcium balance and
      increased dosage of vitamin D, respectively. Sevelamer also decreases serum low
      density lipoprotein cholesterol levels by its bile acid-binding capacity. A long
      term clinical study has demonstrated that the progression of coronary and aortic
      calcification in hemodialysis patients is attenuated by sevelamer. Thus,
      sevelamer offers the promise of impacting cardiac calcification and thereby
      reducing morbidity and mortality of hemodialysis patients.

PMID- 14569165
TI  - Sentinel node biopsy in ectopic breast cancer.

PMID- 14569166
TI  - Narrow time-window dual-point 18F-FDG PET for the diagnosis of thoracic
      malignancy.
AB  - Dual time-point imaging has been proposed as a means of improving the accuracy of
      2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG PET) for
      the diagnosis of malignant pulmonary nodules. The purpose of this study was to
      evaluate a dual time-point protocol that has a narrow time window between its
      initial and its delayed imaging sessions. All patients examined during a 16-month
      time period, either for the diagnosis of a radiographically indeterminate
      thoracic lesion or for the staging of non-small-cell carcinoma, were included in
      the study provided that they completed the dual-point protocol and had either
      biopsy evidence of malignancy, biopsy evidence of a benign condition involving
      the thoracic lesion of concern, or clinical and radiographic follow-up consistent
      with the absence of malignancy. The entire study population was further divided
      into a central subpopulation, whose index lesions were adjacent to or within the
      hilum or mediastinum, and a peripheral subpopulation, whose index lesions were
      non-central. The maximum standardized uptake value (SUV) was measured for each
      lesion, and various body surface areas (BSAs) and glucose corrections on the SUV
      were compared using discriminant analysis. BSA corrected SUVs for the initial
      (iSUV) and the delayed (dSUV) imaging sessions, along with their absolute
      difference (deltaSUV) and fractional difference (fSUV) were also compared using
      discriminant analysis and receiver operating characteristic (ROC) analysis. The
      study population consisted of 132 patients, of whom 81 had malignancy and 51 were
      classified as having a benign condition. Thirty-three index lesions were central
      and 99 were peripheral; 109 had visible uptake and 23 had such low uptake that
      they were not visible above background. The mean time (+/-SD) between initial and
      delayed imaging for the visible lesions was 31.1+/-9.4 min. With respect to the
      entire study population, the BSA replacement for body weight gave the best
      performance among the various SUV corrections examined. In addition, the BSA
      corrected delayed SUV (dSUV) gave a performance superior to either initial SUV
      (iSUV), absolute difference in SUV (deltaSUV) and fractional difference in SUV
      (fSUV) alone. Performance gains achieved by BSA correction and by dSUV appeared
      to derive primarily from the central subpopulation, thereby indicating that
      central lesions tend to behave differently to peripheral ones. For the central
      subpopulation, ROC analysis also demonstrated improved detection of malignancy
      from dual-point imaging. The best performance was achieved when the BSA corrected
      dSUV was at least 2.4, or when the fSUV showed at least a 5% increase from
      initial to delayed imaging. With the optimal combined dSUV/fSUV strategy, the
      area under the ROC curve was 0.99, as opposed to 0.96 for dSUV alone, or 0.93 for
      iSUV alone. The ability of 18F-FDG PET to discriminate between benign and
      malignant conditions of the central thorax can be improved by correcting the SUV
      for BSA and by increasing the 'incubation time' between 18F-FDG injection and
      imaging, or by performing narrow time-window dual-point imaging.

PMID- 14569167
TI  - Can FDG PET be used to successfully direct preoperative biopsy of soft tissue
      tumours?
AB  - Magnetic resonance imaging (MRI) has been the most useful tool in the anatomical
      definition of soft tissue sarcoma, although there remains the problem of defining
      the lesions as benign or malignant. The management of such lesions requires
      biopsy prior to surgical resection. If the most malignant area could be defined
      more accurately, then this area could be targeted for biopsy. Fluorodeoxyglucose
      positron emission tomography (FDG PET) has been found to be useful in identifying
      malignancy and variations in grade in soft tissue masses. The aim of this study
      was to assess the use of FDG PET scanning with or without co-registered MRI to
      indicate the most appropriate biopsy site. Twenty consecutive patients presented
      with soft tissue masses with clinical signs of malignancy. All patients underwent
      MRI and FDG PET scanning and the two images were co-registered. A biopsy site
      that was the most likely to be malignant was defined on the PET scan. All
      patients underwent an initial biopsy and then complete surgical resection of the
      mass. The histological results from the mass were compared with those from the
      biopsy specimen obtained from the site suggested by the PET scan. In malignant
      masses the biopsy site suggested by the FDG PET scan was found to be
      representative of the most malignant site on the whole mass histology. Benign
      lesions had low or no FDG uptake. In no case did the co-registered image add
      significantly to the appropriate biopsy site. FDG PET can be used to
      appropriately direct biopsy in soft tissue sarcoma and potentially may lead to
      computed tomography/MRI directed outpatient biopsy prior to definitive treatment.

PMID- 14569168
TI  - White cell scanning for inflammatory bowel disease: are biochemical markers
      useful referral criteria?
AB  - The aim of this study was to determine whether biochemical markers for
      inflammation could prove effective in identifying the most appropriate patients
      with suspected inflammatory bowel disease (IBD) for labelled white cell scanning.
      One hundred and twenty-five patients referred for 99mTc-HMPAO labelled white cell
      scans were investigated. The values of C-reactive protein (CRP), antichymotrypsin
      (ACT) and acid glycoprotein (AGP) were measured in 73 patients, AGP and CRP in 10
      and CRP only in a further 42. Sensitivity and specificity of each test were
      calculated using the white cell scan result as the 'gold standard'. ACT had the
      highest specificity (1.0), but the lowest sensitivity (0.27) of the three
      markers. CRP (using specified limits) had the lowest specificity (0.67) and the
      highest sensitivity (0.79). The corresponding values for AGP are 0.87 and 0.48.
      The low sensitivity of ACT and AGP preclude them from being useful referral
      criteria. CRP (using specified limits) is the most sensitive marker, but not
      sensitive enough to be useful as a referral indicator. However, by lowering the
      upper limit of normal to 5 mg.l-1, the sensitivity of the test increases to 0.96.
      Using this threshold to select the patients, 30% would not have been scanned and
      only one patient out of the 22 with IBD would have been missed. Where there is
      high demand for white cell scans this may provide a useful strategy for
      rationalizing the requests with minimal consequence on clinical management.

PMID- 14569169
TI  - 111In oxine labelled mesenchymal stem cell SPECT after intravenous administration
      in myocardial infarction.
AB  - Mesenchymal stem cells (MSCs) have shown therapeutic potential if successfully
      delivered to the intended site of myocardial infarction. The purpose of this
      pilot study was to test the feasibility of 111In oxine labelling of MSCs and
      single photon emission computed tomography (SPECT) imaging after intravenous
      administration in a porcine model of myocardial infarction. Adult farm pigs (n=2)
      were subjected to closed chest experimental myocardial infarction. 111In oxine
      labelled MSCs (1 x 10(7) to 2 x 10(7) cells) were infused intravenously, and
      SPECT imaging was performed initially and on days 1, 2, 7 and 14. High quality
      SPECT images were obtained through 2 weeks of imaging. High initial MSC
      localization occurred in the lungs and slow progressive accumulation occurred in
      the liver, spleen and bone marrow. Renal activity was mild and persistent
      throughout imaging. No appreciable accumulation occurred in the myocardium. It is
      concluded that 111In oxine radiolabelling of MSCs is feasible, and in vivo
      imaging with SPECT provides a non-invasive method for sequentially monitoring
      cell trafficking with good spatial resolution. Because intravenous administration
      of MSCs results in significant lung activity that obscures the assessment of
      myocardial cell trafficking, alternative routes of administration should be
      investigated for this application.

PMID- 14569170
TI  - An assessment of wall motion, perfusion and glucose metabolism in recent
      myocardial infarction: a comparison in patients with and without
      revascularization.
AB  - The aim of this study was to compare the extent and severity of wall motion
      abnormalities, perfusion and glucose metabolism, in recent myocardial infarction
      in patients with and without revascularization. Forty-nine patients were studied
      (82% men; mean age 58 years) by using echocardiography, 201Tl single photon
      emission computed tomography (SPECT) rest and redistribution, and 2-[18F]fluoro-2
      deoxy-D-glucose (18F-FDG) SPECT at a mean of 9.2 days (range, 1-24 days) after
      myocardial infarction. Twenty-seven of the 49 patients underwent
      revascularization while the other 22 received medical therapy before
      echocardiography and studies using radionuclides. A contrast angiogram was
      obtained for each patient. A follow-up echocardiogram at 3 months was obtained
      for 44 patients. Images were read blindly, using a 17 segment model, with semi
      quantitative analysis. In the whole group, the extent of hypokinesia was 15%+/-14
      (mean+/-SD); the extent of mild defects was determined as 5%+/-6 by using 201Tl
      at rest, 6%+/-9 by using 201Tl redistribution, and 4%+/-6 by using 18F-FDG
      (P<0.0005, echocardiogram/radionuclides). Echocardiography showed that the extent
      of akinesia-dyskinesia was 16%+/-18 in revascularized patients and 28%+/-18 in
      non-revascularized patients (P=0.017). With regard to moderate and severe
      defects, 201Tl rest showed 19%+/-16 and 28%+/-17, respectively (P=0.047); 201Tl
      redistribution 17%+/-15 and 26%+/-15, respectively (P=0.043); and 18F-FDG 17%+/
      13 and 24%+/-15, respectively (NS). In echocardiography, the extent of
      hypokinetic segments decreased from 16%+/-15 at baseline to 10%+/-11 at 3 months
      (P=0.045), in revascularized patients. It is concluded that, in recent myocardial
      infarction, hypokinesia extent on echocardiogram is greater than mild perfusion
      or metabolic defect extent, reflecting stunning and so the use of radionuclide
      techniques appear more accurate for defining the extent of myocardial infarction.
      Non-revascularized patients showed a significantly greater extent of akinesia
      dyskinesia and moderate-severe perfusion defects than did revascularized
      patients, which can be considered a result of therapy. It is suggested that 201Tl
      rest perfusion be used for the assessment of myocardial infarction soon after
      revascularization.

PMID- 14569171
TI  - Clinical significance and outcome of one or two rib lesions on bone scans in
      breast cancer patients without known metastases.
AB  - The presence of one or two rib lesions on bone scans of post-treatment breast
      cancer patients without known metastases often makes clinical decision making
      problematic. The aim of this study was to identify skeletal metastasis predictors
      that might help the management of these patients. We recruited post-treatment
      breast cancer patients without overt metastases whose bone scans showed (1) one
      or two rib hot spots, or (2) one rib lesion and a concurrent bone abnormality.
      Their clinical and serial scintigraphic data were collected, reviewed and
      evaluated for correlations. After their first abnormal bone scans, 23 patients
      (11 of the 77 patients initially with one rib lesion (incidence, 14.3%), three of
      the 27 patients with two rib lesions (incidence, 11.1%), and nine of the 11
      patients with one rib lesion plus a concurrent bone abnormality (incidence,
      81.8%)) developed multiple bone metastases within 2 years of the initial rib
      lesions in all but one case. Univariate analyses revealed that a concurrent bone
      lesion other than the rib, direct tumour invasion to the chest wall or skin, and
      10 or more lymph nodes involved were associated with increased risks of bone
      metastases whereas longer persistence of the rib lesions was associated with a
      lower risk. Multivariate proportional hazard analyses indicated that patients
      with a concurrent bone lesion other than the rib (relative risk (RR)=39.65; 95%
      confidence interval (CI)=8.13-193.28), 10 or more lymph nodes involved (RR=13.49;
      95% CI=2.09-86.91), and no radiotherapy (RR=7.59; 95% CI=2.11-27.39) were more
      likely to have bone metastases, while those with longer persistence of the rib
      lesions (RR=0.92; 95% CI=0.84-0.98) and longer time interval between surgery and
      the rib lesion detection (RR=0.96; 95% CI=0.94-0.99) were less likely. We have
      identified clinical features applicable to risk stratification. High incidence of
      bone metastases was noted in patients with one rib lesion and a concurrent bone
      abnormality. Regular follow-up for 2 years after detection of rib lesions is
      recommended, especially for those with risk factors.

PMID- 14569172
TI  - Novel tumortropic ester derivatives of 99mTc(V) mesodimercapto succinic acid with
      low affinity for bone tissue.
AB  - Starting from our previous finding that 99mTc(V) dimercaptosuccinic acid
      (99mTc(V)-DMSA), a useful agent for the localization of osteosarcoma and bone
      metastases, loses its bone affinity when one ester group is introduced into the
      complex we studied the impact of esterification in more detail. This paper
      reports on the evaluation of various ester complexes of 99mTc(V)-DMSA in rats and
      tumour-bearing nude mice with regard to their tumour retention and improvement of
      the tumour to tissue ratios. The distribution patterns of the complexes
      [99mTcO(DMSA)2]- (A), [99mTcO(DMSA/DMSEt)]- (B) and [99mTcO(DMSEt)2]- (C) are
      gradually changed with the number of ester groups in the anionic complex.
      However, the asymmetric diester complex [99mTcO(DMSA/DMSEt2)]- (D) is very slowly
      cleared, especially from the blood of nude mice. Moreover, this complex differs
      significantly from the symmetrical complex C in its elimination behaviour from
      the liver and kidneys. The tumour uptake is maintained with complexes that
      contain one or two non-hydrolysable ester functions. Preliminary biodistribution
      studies of the monoethyl and diethyl ester complexes B, C and D in comparison
      with A in tumour-bearing nude mice showed similar uptake into the human squamous
      cell carcinoma (FaDu) as well as into the human colonic cell carcinoma (HT29) of
      nude mice. The low bone accumulation of B, C and D results in excellent tumour-to
      bone ratios, e.g., approx. 3:1 for the ester complex B compared to approx. 1:2
      for complex A. Differences were observed in the accumulation and elimination
      behaviour of the complexes A and B in various bone structures of rats. The age
      dependent uptake of A and B was compared in long bone (femur) and in cranial bone
      of rats. The results suggest that 99mTc(V)-DMSA complexes that contain a
      functional ester, and their 188Re analogues, may be superior to 99mTc(V)/188Re(V)
      DMSA in diagnostic and therapeutic nuclear medicine.

PMID- 14569173
TI  - Usefulness of 99mTc ethyl cysteinate dimer brain SPECT to detect abnormal
      regional cerebral blood flow in patients with acute carbon monoxide poisoning.
AB  - 99mTc ethyl cysteinate dimer (99mTc-ECD) brain single photon emission computed
      tomography (SPECT) was used to detect abnormal regional cerebral blood flow
      (rCBF) in patients with acute carbon monoxide (CO) poisoning. Ten patients with
      acute CO poisoning and no past histories of psychoneurological disorders were
      enrolled in this study. After oxygen treatment, all of the 10 patients were
      investigated using 99mTc-ECD brain SPECT and brain computed tomography (CT) scan.
      Brain CT scan findings were normal in all of the 10 patients. 99mTc-ECD brain
      SPECT showed the hypoperfusion lesions of the basal ganglia and brain cortex in
      five and seven patients, respectively. Only three of the 10 patients had normal
      99mTc-ECD brain SPECT findings. This study suggests that, in comparison with
      brain CT scan, 99mTc-ECD brain SPECT is a better tool for the early detection of
      hypoperfusion brain lesions in acute CO poisoning in patients with normal brain
      CT findings.

PMID- 14569174
TI  - 99mTc-MAG3 diuretic renography in children: a comparison between F0 and F+20.
AB  - The aim of this work was to compare the quality of renal drainage obtained with
      two well-described procedures of diuretic renography (F+20 and F0 tests). We
      selected 36 clinically stable children, aged 10 days to 17 years, with unilateral
      (25) or bilateral (11) hydronephrosis, in whom both F+20 and F0 tests were
      successively performed. In all cases, a late image (PM) was acquired after
      micturition and after changing the position of the patient. The following
      parameters were calculated: the time to the maximum of the basic renogram (Tmax);
      and the normalized residual activity (NORA) and output efficiency (OE) at the end
      of the 20 min renogram, at the end of the furosemide test (35 min) and on the PM
      image. In F+20, the renal drainage was better on the PM image than at the end of
      the diuretic renogram, whereas, in F0, the renal drainage was better on the PM
      image than at the end of the 20 min diuretic renogram. When comparing F0 and
      F+20, both OE and NORA parameters revealed slightly better drainage at the end of
      the 20 min F0 renogram than at the end of the 35 min F+20 diuretic renogram. The
      drainage obtained on the late post-voiding image was comparable for both F0 and
      F+20 tests. In conclusion, the quality of drainage obtained during the F+20 and
      F0 procedures can easily be compared using both OE and NORA. A very similar
      quality of drainage was reached for both procedures when considering only the PM
      image. This PM view remains mandatory irrespective of the timing of the
      furosemide injection and despite the use of tracers with a high extraction rate.

PMID- 14569175
TI  - Physical characteristics of low and medium energy collimators for 123I imaging
      and simultaneous dual-isotope imaging.
AB  - Septal penetration of high energy photons may degrade 123I images obtained with a
      low energy collimator. We evaluated the physical characteristics of a low energy,
      high resolution (LEHR) collimator, special LEHR (SLEHR) collimator, and medium
      energy collimator for 123I studies. The cross-talk of 99mTc and 123I into the
      201Tl window was also examined. Sensitivity and spatial resolution were measured
      with each collimator. Point sources of 99mTc and 123I were imaged at various
      source-collimator distances using multiple energy windows, and the effects of
      collimator choice on energy spectrum and spatial distribution of photopeak counts
      were assessed. For 99mTc, both sensitivity and resolution were similar with the
      low energy collimators, and higher sensitivity and lower resolution were observed
      with the medium energy collimator. For 123I, the full width at tenth maximum was
      larger for 123I than for 99mTc when using the LEHR collimator. Acquisitions with
      multiple energy windows revealed severe degradation due to septal penetration in
      imaging 123I with the LEHR collimator, especially at short distances. The
      degradation was reduced with the SLEHR collimator and further with the medium
      energy collimator. In both 99mTc and 123I imaging, cross-talk into the 201Tl
      window was larger at shorter distances and the largest with the LEHR collimator.
      In conclusion, variation in collimator geometry causes differences in the effect
      of septal penetration on 123I images and in cross-talk into the 201Tl window. The
      SLEHR collimator may be suitable for use in high resolution 123I imaging and
      simultaneous 99mTc/201Tl imaging. Use of the medium energy collimator appears to
      be preferable in quantitative 123I studies.

PMID- 14569176
TI  - Epidemiology and drinking water: are we running dry?

PMID- 14569177
TI  - HIPAA: the end of epidemiology, or a new social contract?

PMID- 14569178
TI  - Nitrate in public water supplies and the risk of colon and rectum cancers.
AB  - BACKGROUND: Nitrate is a widespread contaminant of drinking water, but its
      potential health effects are unclear. In the body, nitrate is reduced to nitrite,
      which can react with amines and amides by nitrosation to form N-nitroso
      compounds, known animal carcinogens. N-nitroso compound formation is inhibited by
      certain nutrients, such as vitamin C, and increased by meat intake. METHODS: We
      investigated the association of nitrate in public water supplies with incident
      colon and rectum cancers in a case-control study conducted in Iowa from 1986 to
      1989. Nitrate levels in Iowa towns were linked to the participants' water source
      histories. We focused our analyses on the period from 1960 onward, during which
      nitrate measurements were more frequent, and we restricted analyses to those
      persons with public water supplies that had nitrate data (actual or imputed) for
      greater than 70% of this time period (376 colon cancer cases, 338 rectum cancer
      cases, and 1244 controls). RESULTS: There were negligible overall associations of
      colon or rectum cancers with measures of nitrate in public water supplies,
      including average nitrate and the number of years with elevated average nitrate
      levels. For more than 10 years with average nitrate greater than 5 mg/L, the odds
      ratio (OR) for colon cancer was 1.2 (95% confidence interval [CI] = 0.9-1.6) and
      for rectum the OR was 1.1 (CI = 0.7-1.5). However, nitrate exposure (>10 years
      with average nitrate >5 mg/L) was associated with increased colon cancer risk
      among subgroups with low vitamin C intake (OR = 2.0; CI = 1.2-3.3) and high meat
      intake (OR = 2.2; CI = 1.4-3.6). These patterns were not observed for rectum
      cancer. CONCLUSIONS: Our analyses suggest that any increased risk of colon cancer
      associated with nitrate in public water supplies might occur only among
      susceptible subpopulations.

PMID- 14569179
TI  - Trihalomethane levels in home tap water and semen quality.
AB  - BACKGROUND: Trihalomethanes (THMs) are byproducts of drinking water chlorination
      whose effects on semen quality have not been previously studied in humans.
      METHODS: We examined the relationship of THMs to semen quality in 157 healthy men
      from couples without known risk factors for infertility. Total THM (TTHM) levels
      were assigned based on water utility measurements taken during the 90 days
      preceding semen collection. We analyzed continuous semen parameters in relation
      to total and individual THMs, adjusting for potential confounders by using
      repeated measures analyses. RESULTS: TTHM level was not associated with
      decrements in semen quality. Percent normal morphology decreased and percent head
      defects increased at higher levels of an ingestion metric (TTHM multiplied by
      cold home tap water consumption). At the highest level of the ingestion metric
      (>160 mug/L x glasses/day, which is equivalent to >2 glasses/day of water
      containing 80 mug/L) we observed a difference of -7.1 (95% confidence interval = 
      12.7 to -1.6) for percent morphologically normal sperm compared with the lowest
      level (</= 40 mug/L x glasses/day). Of the individual THMs, bromodichloromethane
      exposure was inversely related to linearity (a motility parameter); we observed a
      small decrease (beta = -0.09, SE 0.04) for every unit increase in
      bromodichloromethane. CONCLUSION: Although our study had a limited exposure
      assessment and a selective sample, our results suggest the need for further study
      of the effects of THMs on semen quality.

PMID- 14569180
TI  - The association between fruit and vegetable consumption and peripheral arterial
      disease.
AB  - BACKGROUND: High fruit and vegetable consumption has been associated with a lower
      risk of cardiovascular diseases, but few studies have focused on peripheral
      arterial disease. In this study, we evaluated the association of consumption of
      fruits and vegetables with peripheral arterial disease. METHODS: In a cohort of
      44,059 men initially free of cardiovascular disease and diabetes, we documented
      295 cases of peripheral arterial disease during a 12-year follow-up. Fruit and
      vegetable consumption was assessed by food frequency questionnaire. RESULTS: In
      the age-adjusted model, men in the highest quintile had a relative risk of 0.55
      (95% confidence interval = 0.38-0.80) for overall fruit and vegetable intake,
      0.52 (0.36-0.77) for fruit intake, and 0.54 (0.36-0.81) for vegetable intake,
      compared with those in the lowest quintile of intake. However, the associations
      were greatly weakened after adjustment for smoking and other traditional
      cardiovascular disease risk factors. Comparing men in the highest quintile versus
      the lowest quintile, relative risks and 95% confidence intervals were 0.95 (0.62
      1.44) for overall fruit and vegetable intake, 0.97 (0.64-1.48) for fruit intake,
      and 0.76 (0.50-1.17) for vegetable intake. CONCLUSIONS: We did not find evidence
      that fruit and vegetable consumption protects against peripheral arterial
      disease, although a modest benefit cannot be excluded.

PMID- 14569181
TI  - Rising rates of hospital admissions for atrial fibrillation.
AB  - BACKGROUND: Atrial fibrillation is a common arrhythmia associated with excess
      morbidity and mortality. We studied temporal changes in hospital admission rates
      for atrial fibrillation using data from a prospective population-based cohort
      study spanning 2 decades (the Copenhagen City Heart Study). METHODS: The study
      included baseline data collected in 1981 through 1983 on 10,955 persons age 40 to
      79 years and baseline data collected in 1991 through 1994 on 7212 persons age 40
      to 79 years. We used hospital diagnosis data from the Danish National Hospital
      Discharge Register to determine the rate of first hospital admission for atrial
      fibrillation during 7 years following each of the 2 baseline data collecting
      periods. Changes in admission rates were analyzed using Cox proportional hazard
      models. RESULTS: During the 2 7-year periods, 379 subjects were admitted with a
      hospital diagnosis of atrial fibrillation. The rate of hospital admissions for
      atrial fibrillation increased among both men and women from the first to the
      second period (relative risk = 1.6; 95% confidence interval = 1.3-1.9 [adjusted
      for age, sex, prior myocardial infarction, arterial hypertension, diabetes
      mellitus, electrocardiographic left ventricular hypertrophy, decreased lung
      function, smoking, height, and weight]). CONCLUSION: During the latest 10 to 20
      years, there has been a 60% increase in hospital admissions for atrial
      fibrillation independent of changes in known risk factors. This increase could
      result from changes in admission threshold or coding practices, or it could
      reflect a genuine increase in the population incidence of atrial fibrillation.

PMID- 14569183
TI  - Marginal structural models as a tool for standardization.
AB  - In this article, we show the general relation between standardization methods and
      marginal structural models. Standardization has been recognized as a method to
      control confounding and to estimate causal parameters of interest. Because
      standardization requires stratification by confounders, the sparse-data problem
      will occur when stratified by many confounders and one then might have an
      unstable estimator. A new class of causal models called marginal structural
      models has recently been proposed. In marginal structural models, the parameters
      are consistently estimated by the inverse-probability-of-treatment weighting
      method. Marginal structural models give a nonparametric standardization using the
      total group (exposed and unexposed) as the standard. In epidemiologic analysis,
      it is also important to know the change in the average risk of the exposed (or
      the unexposed) subgroup produced by exposure, which corresponds to the exposed
      (or the unexposed) group as the standard. We propose modifications of the weights
      in the marginal structural models, which give the nonparametric estimation of
      standardized parameters. With the proposed weights, we can use the marginal
      structural models as a useful tool for the nonparametric multivariate
      standardization.

PMID- 14569182
TI  - Cognitive functioning as a predictor of ischemic stroke incidence.
AB  - BACKGROUND: Some studies have suggested that cognitive impairment is related to
      subsequent stroke incidence. The present study investigated the role of cognitive
      impairment as a predictor of ischemic stroke incidence in the Atherosclerosis
      Risk in Communities (ARIC) cohort. METHODS: The study population consisted of
      11,958 men and women 48-67 years of age in 4 U.S. communities, followed from
      January 1, 1990 through December 31, 1997. Cognitive performance was evaluated at
      the second (1990-1992) visit of the ARIC Study using 3 instruments. We identified
      incident strokes by means of hospital record and death certificate reviews, as
      well as annual telephone follow up. RESULTS: We found no consistent associations
      or trends between any of the cognitive test results and ischemic stroke incidence
      after multiple adjustment for confounding variables. Hazard ratios for the lowest
      compared with the highest quartiles were 1.5 (95% confidence interval [CI] = 0.9
      2.6), 1.1 (95% CI = 0.6-2.1), and 1.0 (95% CI = 0.6-1.8) for the Delayed Word
      Recall Test, Digit Symbol Subtest of the Wechsler Adult Intelligence Scale
      Revised, and Word Fluency Test, respectively. CONCLUSIONS: The findings of the
      present study of relatively young subjects did not replicate the association
      between cognitive impairment and stroke incidence found in studies in older
      populations. This could be the result of the younger ages of our cohort members
      or the differences in cognitive tests.

PMID- 14569184
TI  - Residential proximity to industrial plants and non-Hodgkin lymphoma.
AB  - BACKGROUND: A U.S. analysis suggested a relation between self-reported
      residential proximity to industrial plants and non-Hodgkin lymphoma (NHL) risk.
      METHODS: Using lifetime residential histories collected from a population-based
      sample of 1499 Canadians with newly diagnosed, histologically confirmed NHL and
      5039 population controls, we evaluated the association of residential proximity
      to 7 types of major heavy industry with NHL risk. RESULTS: Overall, having lived
      within 0.8 km or within 3.2 km of an industrial plant was not associated with
      increased NHL risk. For the follicular subtype of NHL, an odds ratio (OR) of 1.48
      (95% confidence interval [CI] = 1.10-1.99) was observed for women who had lived
      within 3.2 km (83 cases/689 controls). ORs for NHL were elevated for proximity
      within 3.2 km of copper smelters (OR = 5.1; CI = 1.5-17.7; 7 cases, 4 controls)
      and within 0.8 km of sulfite pulp mills (OR = 3.7; CI = 1.5-9.4; 9 cases, 10
      controls). CONCLUSIONS: We have identified possible associations between NHL and
      proximity to industrial plants, which could be the result of chance or other
      factors associated with proximity. Studies are needed to confirm these
      associations and to determine whether residential proximity can result in
      meaningful exposure.

PMID- 14569185
TI  - The HER2 I655V polymorphism and breast cancer risk in Ashkenazim.
AB  - SUMMARY: BACKGROUND Over-expression of the human epidermal growth factor receptor
      2 (Her2) protooncogene is associated with poor prognosis among female patients
      with breast cancer. A polymorphism in the HER2 gene (I655V) has been associated
      with an elevated risk of breast cancer in some ethnic groups. METHODS Subjects
      from a community-based study of 5318 Ashkenazim from the Washington, DC area were
      selected for analysis of the I655V HER2 germline polymorphism. We estimated age
      specific breast cancer risk from HER2 I655V based on the family history data,
      using the female first-degree relatives of the study participants and a novel
      extension of the kin cohort method. RESULTS The estimated cumulative risk of
      breast cancer to age 70 was approximately 30% higher among HER2 I655V carriers
      than noncarriers (RR = 1.33; 95% confidence interval [CI] = 1.03-1.83). The
      effect of the allele seems stronger at younger ages (among women younger than 50
      years, RR = 2.11; CI = 1.39-3.28) and especially among younger women with a
      family history of breast cancer (RR = 8.9; CI = 1.9-19.7). Increased risk of
      breast cancer associated with the I655V allele was also observed among BRCA1/2
      mutation carriers, although these results are based on small numbers. CONCLUSION
      These analyses suggest that the HER2 valine allele might be associated with
      increased risk of breast cancer, especially in young women and in women with a
      family history of the disease.

PMID- 14569186
TI  - Hypospadias in California: trends and descriptive epidemiology.
AB  - BACKGROUND: The occurrence of hypospadias has been reported to be increasing. The
      objectives of this study were to extend the literature on the descriptive
      epidemiology of hypospadias and to determine whether its birth prevalence
      increased in California in recent years. We used actively ascertained, population
      based data for which detailed clinical descriptions permitted careful phenotypic
      classifications. METHODS: We examined registry data on 5838 male live births and
      stillbirths that occurred in California from 1984 through 1997. To reduce
      pathogenic heterogeneity, cases were classified as mild, severe, or not otherwise
      specified based on the anatomic position of the urethral opening. We also
      classified cases as isolated or nonisolated based on the presence and type of
      accompanying malformations. We used multivariable Poisson regression analysis to
      examine time trends and risk factors. RESULTS: There was no evidence for an
      increase in prevalence of any of the case groups between 1989 and 1997. The
      adjusted relative risk (RR) for change in prevalence per year of isolated severe
      cases was 0.99 (95% confidence interval = 0.96-1.03). Adjusted RRs indicated
      increased risks for specific types of hypospadias with maternal non-Hispanic
      white race-ethnicity, higher education, older age, and nulliparity. Delivery
      before 37 weeks and multiple births tended either not to be associated with risk
      or to be associated with reduced risk. Lower birthweight was associated with
      increased risk for all case groups. CONCLUSIONS: This study suggests that
      hypospadias prevalence has not been increasing in California in recent years.
      Differences by phenotype suggest that examining certain phenotypes separately
      could help to understand hypospadias etiology.

PMID- 14569187
TI  - Sun exposure as a risk factor for nuclear cataract.
AB  - BACKGROUND: Cataracts are the leading cause of blindness and visual impairment
      throughout the world. An association of sun exposure with cortical cataract has
      been well established, but the association with nuclear cataract remains unclear.
      METHODS: This case-control study was nested within the Nambour (Australia) Trial
      of Skin Cancer Prevention conducted between 1992 and 1996. We compared 195 cases
      who had a nuclear opacity of grade 2.0 or greater with 159 controls. Structured
      questionnaires were used to ascertain lifetime sun exposure history, eyeglasses
      and sunglasses use, and potentially confounding variables such as education and
      smoking. RESULTS: There was a strong positive association of occupational sun
      exposure between the ages of 20 and 29 years with nuclear cataract (odds ratio =
      5.9; 95% confidence interval = 2.1-17.1). Exposure later in life resulted in
      weaker associations. Wearing sunglasses, particularly during these early years,
      afforded some protective effect. CONCLUSIONS: This study provides new evidence to
      support a link between sun exposure and nuclear cataract. Risk was highest among
      those with high sun exposure at younger ages.

PMID- 14569188
TI  - Lead exposure biomarkers and mini-mental status exam scores in older men.
AB  - BACKGROUND: Lead is neurotoxic; yet, whether cognitive decline in older persons
      is associated with lead exposure is unknown. We studied whether lead exposure
      biomarkers are associated with cognitive test scores, as well as the modifying
      effects of age on the lead-cognition relationship. METHODS: Lead exposure
      biomarkers and Mini-Mental Status Exam (MMSE) scores were measured among subjects
      in the Normative Aging Study. Multiple linear and logistic regression analyses
      were performed to examine the cross-sectional association of these 2 variables.
      RESULTS: We found an odds ratio (OR) of 2.1 for MMSE <24 with an increase from
      the lowest to the highest quartile of patella lead levels (95% confidence
      interval [CI] = 1.1 to 4.1). From the lowest to the highest quartile of blood
      lead the OR for low MMSE was 3.4 (CI = 1.6 to 6.2). There was an interaction
      between lead biomarkers and age. Among subjects in the lowest quartile of patella
      lead levels, MMSE score decreased by 0.03 points per year (CI = -0.07 to 0.005),
      whereas in the highest quartile, MMSE score decreased by 0.13 points per year (CI
      = -0.19 to -0.07). Similar interactions were found between blood lead levels and
      age. CONCLUSIONS: Increased levels of lead in bone and blood are inversely
      associated with cognitive performance among older men. Lead exposure might
      accelerate age-associated cognitive decline.

PMID- 14569189
TI  - Second-hand smoke exposure and blood lead levels in U.S. children.
AB  - BACKGROUND: Lead is a component of tobacco and tobacco smoke, and smokers have
      higher blood lead levels than do nonsmokers. METHODS: We examined the relation
      between second-hand smoke exposure and blood lead levels in a nationally
      representative sample of 5592 U.S. children, age 4-16 years, who participated in
      the Third National Health and Nutrition Examination Survey (1988-1994). Linear
      and logistic regression modeling was used to adjust for known covariates.
      RESULTS: Geometric mean blood lead levels were 1.5 mug/dL, 1.9 mug/dL, and 2.6
      mug/dL for children with low, intermediate, and high cotinine levels,
      respectively. The adjusted linear regression model showed that geometric mean
      blood lead levels were 38% higher (95% confidence interval [CI] = 25-52%) in
      children with high cotinine levels compared with children who had low cotinine
      levels. The logistic regression models showed that children with high cotinine
      levels were more likely to have blood lead levels >/=10 mug/dL than were children
      with low cotinine levels (odds ratio [OR] = 4.4; CI = 1.9-10.5). CONCLUSIONS:
      Second-hand smoke could be associated with increased blood lead levels in U.S.
      children aged 4-16 years.

PMID- 14569191
TI  - Self-reported family history of cancer: the utility of probing questions.
AB  - BACKGROUND: Many studies of familial aggregation of cancer have relied on self
      reported cancer family history data because verification through medical records
      was not feasible. Self-reported data might be nonspecific and prone to errors,
      although of high quality for certain cancers. We evaluated the utility of a brief
      follow-up survey to elicit further details regarding uncertain cancer conditions.
      METHODS: We reviewed all of the cancer family histories reported by 13,972
      survivors participating in the Childhood Cancer Survivor Study. There were 533
      affected relatives (obtained from 500 cases) identified as having uncertain
      cancer histories. Of these 500 cases, 386 (77%) were successfully recontacted.
      They completed a 5- to 7-minute telephone survey containing focused, probing
      questions regarding their 406 relatives with uncertain cancer conditions. Two
      investigators independently reviewed the survey responses. RESULTS: A disease
      site and malignancy status could be determined for 81% (331 of 406) of the
      relatives. Among the 312 relatives with a single uncertain cancer condition, the
      additional survey identified 58% as having a malignant condition with a known
      primary site, 7% as having a malignant condition with an undetermined primary
      site, 22% as having a benign condition, and 13% for whom no further clarification
      was possible. Among the 94 relatives with multiple reported cancers, 64% were
      found to represent a single diagnosis. CONCLUSIONS: Incorporation of additional
      probing questions into the initial family history interview would improve the
      ability to classify cancer reports by site and malignancy status. The utility of
      these additional questions could vary by the site and specificity of the initial
      cancer reports.

PMID- 14569190
TI  - Residence near a major road and respiratory symptoms in U.S. Veterans.
AB  - BACKGROUND: There is evidence that exposure to motor vehicle exhaust is
      associated with respiratory disease. Studies in children have observed
      associations with wheeze, hospital admissions for asthma, and decrements in
      pulmonary function. However, a relationship of adult respiratory disease with
      exposure to vehicular traffic has not been established. METHODS: We studied a
      sample of U.S. male veterans drawn from the general population of southeastern
      Massachusetts. Information on respiratory symptoms and potential risk factors was
      collected by questionnaire. We assessed distance from residential addresses to
      major roadways using geographic information system methodology. RESULTS:
      Adjusting for cigarette smoking, age, and occupational exposure to dust, men
      living within 50 m of a major roadway were more likely to report persistent
      wheeze (odds ratio [OR] = 1.3; 95% confidence interval [CI] = 1.0-1.7) compared
      with those living more than 400 m away. The risk was observed only for those
      living within 50 m of heavily trafficked roads (>/=10,000 vehicles/24 h): OR =
      1.7; CI = 1.2-2.4). The risk of patients experiencing chronic phlegm while living
      on heavily trafficked roads also increased (OR = 1.4; CI = 1.0-2.0), although
      there was little evidence for an association with chronic cough. This association
      was not dependent on preexisting doctor-diagnosed chronic respiratory or heart
      disease. CONCLUSIONS: Exposure to vehicular emissions by living near busy
      roadways might contribute to symptoms of chronic respiratory disease in adults.

PMID- 14569192
TI  - Estrogen metabolites and the risk of breast cancer in older women.
AB  - BACKGROUND: Women who metabolize a large proportion of their estrogen via the
      16alpha hydroxylation pathway could be at a higher risk of breast cancer. The
      objective of this study was to test the hypothesis that serum concentrations of 2
      hydroxyestrone (2-OHE1) and 16alpha-hydroxyestrone (16alpha-OHE1), as well as
      their ratio, predict the risk of breast cancer in older women. METHODS: We
      performed a case-cohort study of 272 women with confirmed incident breast cancer
      and 291 controls chosen randomly from the cohort. Estrogen metabolites were
      measured in serum collected at the baseline examination and stored at -120
      degrees C. Incident breast cancers were confirmed by medical records and
      pathology reports during an average follow-up of 8.7 years. RESULTS: Mean
      concentrations of 2-OHE1 and 16alpha-OHE1, adjusted for age and body mass index,
      were 3% to 4% higher in cases compared with controls: 2-OHE1 was 176 pg/mL and
      169 pg/mL and 16alpha-OHE1 was 233 pg/mL and 226 pg/mL in cases and controls,
      respectively. There was, however, no difference in the ratio of 2-OHE1 to 16alpha
      OHE1. The risk of breast cancer in women with the highest quartile of this ratio
      compared with those in the lowest quartile was 1.17 (95% confidence interval =
      0.73-1.87). CONCLUSION: The study results do not support the hypothesis that the
      ratio of 2-OHE1 to 16alpha-OHE1 predicts breast cancer risk.

PMID- 14569194
TI  - A conversation with Mervyn Susser. Interview by Nigel Paneth.

PMID- 14569193
TI  - Genotyping patients with recent blood transfusions.
AB  - BACKGROUND: Many studies have used polymerase chain reaction amplification (PCR)
      to genotype for common polymorphisms in intensive-care units (ICUs) where blood
      transfusions are common. Evidence that donor leukocytes in transfused blood can
      be detected by PCR of the recipient blood suggests that this minor population of
      donor white cells (microchimerism) can interfere with genotyping of allelic
      polymorphisms in critically ill transfused patients. To investigate this
      possibility, we assayed DNA extracted from the blood and buccal cells of ICU
      patients for 2 common polymorphisms in the TNF-beta gene and the surfactant
      protein-B (SP-B) gene. METHODS: Study subjects were ICU patients from the
      Massachusetts General Hospital (Boston, MA) enrolled into a study on the
      molecular epidemiology of acute respiratory distress syndrome between January
      1999 and October 2000. Blood and buccal cells were collected and DNA was
      extracted from 145 patients. Genotyping was performed by enzyme digestion and
      pyrosequencing. RESULTS: The Kappa statistics comparing the genotype results from
      blood and buccal cells were 0.98 (95% confidence interval [CI] = 0.94-1.01) for
      TNFB and 0.95 (CI = 0.87-1.02) for SP-B. When the analysis was restricted only to
      the 107 patients who were transfused, the Kappa statistic remained high at 0.97
      (CI = 0.93-1.01) for TNFB and 0.93 (CI = 0.84-1.03) for SP-B. CONCLUSION: We
      conclude that microchimerism from allogeneic blood transfusion is unlikely to
      have major effects on the genotype results of common polymorphisms in large
      molecular epidemiology studies conducted in the critical care setting if DNA is
      collected within a day after transfusions.

PMID- 14569195
TI  - Clinical symptoms in patients with myositis-an acquired metabolic myopathy?

PMID- 14569196
TI  - Physical activity and disablement in the idiopathic inflammatory myopathies.
AB  - PURPOSE OF REVIEW: The sequelae associated with idiopathic inflammatory myopathy
      (IIM) often result in disability and decreased quality of life. Our understanding
      of how exercise mitigates disability may be facilitated through the use of a
      conceptual model. This review describes the enablement-disablement model applied
      to myositis and explores the role of physical activity in the enablement process.
      RECENT FINDINGS: National and international organizations have revised their
      disablement models by acknowledging disability as a relational concept, refining
      the relationship of disability to quality of life, and incorporating the role of
      intervention through the enablement process. Disability associated with IIM may
      be complicated by aging-related comorbidities and decreased physical activity.
      However, data indicate that both short-term and long-term aerobic training
      results in improved aerobic capacity and decreased disability in adults with IIM.
      Strengthening regimens have also resulted in decreased functional limitations and
      disability for adults with polymyositis and dermatomyositis. While comprehensive
      exercise programs have not been shown to exacerbate disease activity or damage in
      people with IIM, their effectiveness for individuals with inclusion body myositis
      (IBM) remains uncertain. SUMMARY: Physical activity constitutes a valuable
      enablement strategy that can reduce disability in adults with IIM. Use of the
      disablement-enablement model and ICF taxonomy in conjunction with outcomes across
      disablement domains may augment further investigation of the effectiveness of
      exercise interventions. Additional research is needed to better understand the
      relationship between disease severity and optimal exercise dosage, the effects of
      long-term exercise in children with IIM, and the physiologic response to exercise
      in people with IBM.

PMID- 14569197
TI  - Cytokines in juvenile dermatomyositis pathophysiology: potential and challenge.
AB  - PURPOSE OF REVIEW: Cytokines are criticalmediators of the immune response. This
      review focuses on cytokine-specific information from children with juvenile
      dermatomyositis, and includes pertinent data from adults with polymyositis and
      dermatomyositis. RECENT FINDINGS: Much of the new data concern the role of
      possible antigens and the definition of genetic control of the immune response in
      juvenile dermatomyositis. Gene expression profile data of DQA1*0501 (present in
      85% of patients) compared with age-matched control subjects show that the initial
      immune response is an interferon-alpha/beta-induced cascade with secondary
      stimulation of interferon-gamma. Specific epitopes of group A beta-hemolytic
      streptococcal M protein, with sequence homology for myosin, elicit both cell
      mediated cytotoxicity and tumor necrosis factor-alpha production when incubated
      with mononuclear cells from children with active juvenile dermatomyositis. Tumor
      necrosis factor-alpha synthesis is increased in juvenile dermatomyositis patients
      with the tumor necrosis factor-alpha-308A allele, and is associated with
      increased thrombospondin-1 (an antiangiogenic agent) production and small vessel
      occlusion in untreated juvenile dermatomyositis. Studies in adults with
      polymyositis and dermatomyositis implicate interleukin-1alpha, transforming
      growth factor-beta, and endothelial cell perturbation early in the disease
      course. Cultured myoblasts were found to produce interleukin-15, which impacts
      local T-cell activation and proliferation. SUMMARY: The limited data suggest that
      a possible viral/microbial antigen may elicit an interferon-alpha/beta-induced
      response, and that antigenic epitopes may be shared. Increased synthesis of tumor
      necrosis factor-alpha, more common in juvenile dermatomyositis with the tumor
      necrosis factor-alpha-308A polymorphism, may augment this response and is
      associated with a wide range of pathologic consequences, as well as disease
      chronicity and calcifications. The muscle fibers themselves can regulate local
      inflammation by production of tumor necrosis factor-alpha, interleukin-15 and
      interleukin-1alpha, and transforming growth factor-beta.

PMID- 14569198
TI  - New molecular research technologies in the study of muscle disease.
AB  - PURPOSE OF REVIEW: To describe the current technologies and progress in DNA
      polymorphism association studies, mRNA expression profiling (microarrays), and
      proteomics with respect to muscle disease, and the increasing impact of public
      access databases of genome-wide information. RECENT FINDINGS: mRNA expression
      profiling is becoming the most mature of the highly parallel molecular
      technologies, with microarrays now able to query the large majority of all genes
      using 1 million oligonucleotide probes built on 1.2-cm2 glass substrates.
      Applications of microarrays to normal muscle physiology and muscle disease are
      discussed. Single nucleotide polymorphism association studies promise to
      determine the predisposition of individuals to acquired muscle disease, including
      sarcopenia and atrophy, although such studies are in their infancy. Proteomics
      technologies do not enjoy the sensitivity and specificity of hybridization, and
      must instead rely on mass spectrometers. Mass spectrometry technology is
      advancing rapidly, although the sensitivity and throughput is far behind that of
      mRNA expression profiling. SUMMARY: As the gene mutations responsible for many
      types of muscular dystrophy and myopathy have been discovered, protein and gene
      testing has been integrated into the standard patient diagnostic workup. Future
      developments will include simpler and less expensive molecular diagnostics,
      advances in the understanding of downstream consequences of these defects, and
      the genetic predispositions underlying acquired muscle disease.

PMID- 14569199
TI  - Anti-aminoacyl tRNA synthetase immune responses: insights into the pathogenesis
      of the idiopathic inflammatory myopathies.
AB  - PURPOSE OF REVIEW: One of the most striking humoral characteristics of the
      idiopathic inflammatory myopathies is the specific targeting of components of the
      translational machinery by the immune system. The most commonly targeted of these
      components are the aminoacyl tRNA synthetase (ARS) molecules. However, the
      relation between the immune responses to these molecules and the pathogenesis of
      the inflammatory myopathies remains obscure. This review will examine recent
      evidence that explores the links between the ARS molecules, inflammation, and
      apoptosis, with the aim of furthering our current understanding of the underlying
      pathogenesis of the myositis syndromes. RECENT FINDINGS: Several of the ARS
      molecules and their proteolytic fragments generated during inflammation and
      apoptosis have recently been shown to possess chemoattractant properties. The
      liberation of these fragments in the muscle microenvironment under certain
      circumstances may provide a proinflammatory context and lead to the influx of
      lymphocytes, macrophages, and specialized antigen-presenting cells to the site of
      muscle injury. The subsequent processing and presentation of these autoantigen
      fragments on major histocompatibility complex class I and II molecules may
      generate an ARS-specific autoimmune response, which may be responsible for
      amplification and propagation of muscle injury in these diseases. SUMMARY: The
      striking association between the inflammatory myopathies and anti-ARS antibodies
      implies a role for the ARS molecules in the pathogenesis of these syndromes.
      Recent data suggest that ARS molecules and their proteolytic fragments generated
      during the cell death process may be responsible for priming and sustaining a
      specific immune response in situ in myositis. How these molecules become altered
      and access the immune system in the disease microenvironment is an area of
      ongoing investigation.

PMID- 14569200
TI  - Skin involvement in dermatomyositis.
AB  - PURPOSE OF REVIEW: Dermatomyositis (DM) is a rare multisystem autoimmune disorder
      of adults and children that primarily affects skin and skeletal muscle.
      Classification systems of dermatomyositis, polymyositis, and the other idiopathic
      inflammatory myopathies focus primarily on features of muscle involvement.
      However, cutaneous disease does not always parallel muscle disease in its onset,
      activity, or response to therapy. This review will describe the distinct
      cutaneous clinical and histopathologic presentation of DM and the relation
      between these cutaneous findings, pathogenesis of DM, and serological subsets of
      DM. RECENT FINDINGS: This review discusses recent findings that have begun to
      elucidate the pathogenesis of DM, including polymorphism of tumor necrosis factor
      alpha 308A allele and maternal fetal microchimerism. The recent description of
      other systemic diseases and drugs causing DM-like eruptions and the recognition
      that DM can resemble other common dermatoses highlights the need for a cutaneous
      biopsy to diagnose and distinguish the cutaneous features of DM. Once diagnosed,
      a number of noninvasive imaging modalities and new cutaneous assessment
      instruments can be used to follow and evaluate patients with DM. SUMMARY:
      Recognition of cutaneous and histopathologic findings in DM is essential for
      prompt and accurate diagnosis and treatment of DM.

PMID- 14569201
TI  - Cell therapies for inherited myopathies.
AB  - PURPOSE OF REVIEW: Cell therapies for inherited myopathies are based on the
      implantation of normal or genetically corrected myogenic cells into the body.
      This review summarizes the recent progress in this field, systematized according
      to the factors important for success. RECENT FINDINGS: In the choice of donor
      cells, myoblasts derived from satellite cells remain the best choice. Some
      studies on the population of muscle-derived stem cells in mice suggested that
      these cells may have some advantages over myoblasts; however, no results
      supporting this advantage have been presented in a primate model. Recent studies
      on bone marrow transplantation as a systemic source of myogenic precursors for
      the treatment of myopathies were disappointing. Concerning donor cell delivery,
      intramuscular myoblast injection remains the only way that can significantly
      introduce exogenous myogenic cells into the muscles. A recent study in primates
      showed some parameters of myoblast injection that could be useful in the human.
      Progress was made in mice to understand the factors that could favor the
      migration of the donor myoblasts in the host muscles. Concerning donor cell
      survival, analysis of immune cell infiltration dynamics allowed a better
      understanding of the factors implicated in early donor cell death. Progress was
      made on the control of acute rejection for myoblast transplantation in primates.
      So far, few mouse experiments have advanced the field of tolerance induction
      toward myogenic cells. SUMMARY: Myoblast transplantation (intramuscular injection
      of satellite cell-derived myoblasts) currently remains the only cell-based
      therapy that has produced promising results in the context of a preclinical model
      such as the nonhuman primate.

PMID- 14569202
TI  - Oxidative Stress: a common denominator in the pathogenesis of amyotrophic lateral
      sclerosis.
AB  - PURPOSE OF REVIEW: Amyotrophic lateral sclerosis, or Lou Gehrig disease, is a
      progressive neurodegenerative disease of adult onset characterized by a loss of
      motor neurons in the spinal cord and motor cortex. In the last several years,
      substantial progress has been made in defining the pathogenesis of motor neuron
      injury and relationships between disease mechanisms and the selective
      vulnerability of the motor neuron in both familial and sporadic forms of
      amyotrophic lateral sclerosis. RECENT FINDINGS: Current theories have shifted
      from a neuron-centered pathology to a focus on the interaction between motor
      neurons and glia, and their respective contributions to pathways implicated in
      amyotrophic lateral sclerosis. Although multiple mechanisms clearly can
      contribute to the pathogenesis of motor neuron injury, recent advances suggest
      that oxidative stress may play a significant role in the amplification, and
      possibly the initiation, of disease. SUMMARY: This article reviews the clinical
      aspects of amyotrophic lateral sclerosis and potential mechanisms of disease
      pathogenesis in the context of recent data supporting a major role for oxidative
      stress throughout the disease course. Evidence suggesting an important role for
      intercellular signaling is emphasized.

PMID- 14569205
TI  - Evaluation and management of alveolitis and interstitial lung disease in
      scleroderma.
AB  - PURPOSE OF REVIEW: In the fibrosing alveolitis of systemic sclerosis, treatment
      decisions depend on prognostic evaluation, which continues to excite considerable
      interest and debate. Advances in the staging of fibrosing alveolitis of systemic
      sclerosis and recent therapeutic studies are discussed in this review. RECENT
      FINDINGS: The decision about whether to start treatment is often the most
      difficult clinical challenge, because many patients have limited pulmonary
      fibrosis that will not necessarily progress. The estimation of disease extent
      (using high-resolution CT) and disease severity (using pulmonary function tests)
      is pivotal. Factors reducing the threshold for treatment, in addition to severe
      disease, include evidence of recent deterioration, a short duration of systemic
      disease, antitopoisomerase antibody positivity, and, in some cases,
      bronchoalveolar lavage findings (although the role of bronchoalveolar lavage
      remains contentious). Histologic appearances at surgical biopsy have little
      prognostic value, with the great majority of patients having nonspecific
      interstitial pneumonia. Best current initial treatment consists of either oral or
      intravenous cyclophosphamide, usually administered with low-dose corticosteroid
      therapy, although the risk of scleroderma renal crisis with low-dose steroid
      therapy requires further evaluation. SUMMARY: Careful prognostic evaluation,
      including the staging of disease severity and the definition of longitudinal
      disease behavior (by serial imaging and pulmonary function tests), is central to
      the formulation of a logical management plan in fibrosing alveolitis of systemic
      sclerosis. Cyclophosphamide, the best initial treatment currently, is associated
      with significant toxicity, justifying therapeutic studies of other
      immunosuppressive agents and a wide range of anticytokine and antifibrotic
      agents.

PMID- 14569203
TI  - Proposed pathogenetic cascade of inclusion-body myositis: importance of amyloid
      beta, misfolded proteins, predisposing genes, and aging.
AB  - PURPOSE OF REVIEW: Sporadic inclusion-body myositis, the most common muscle
      disease of older persons, is of unknown cause, and there is no successful
      treatment. Interest in sporadic inclusion-body myositis has been enhanced by the
      recent identification within the sporadic inclusion-body myositis muscle fibers
      of several abnormally accumulated proteins, which provides novel and important
      clues to the pathogenesis of sporadic inclusion-body myositis. RECENT FINDINGS:
      This article summarizes the most recent findings leading to better understanding
      of the players in the pathogenetic cascade. It is suggested that lymphocytic
      inflammatory component is probably secondary, and it may contribute only slightly
      to muscle fiber damage in sporadic inclusion-body myositis. However, it is
      proposed that the identified abnormal accumulation, aggregation, and misfolding
      of proteins, combined with and perhaps provoked by an aging intracellular milieu,
      more essentially lead to the vacuolar degeneration and atrophy of the muscle
      fibers that are specific to sporadic inclusion-body myositis. Abnormal
      accumulations of the amyloid-beta precursor protein and of its proteolytic
      fragment, amyloid-beta, associated with the aging cellular muscle fiber
      environment, appear to be key pathogenic events. SUMMARY: In conceptualizing a
      treatment for sporadic inclusion-body myositis, the accumulations of amyloid
      beta42 and other unfolded proteins are now phenomena to be reckoned with. One
      would like to stop intracellular increase of the unfolded/misfolded proteins by
      reducing their formation and/or increasing their disposal. In addition, the
      identification of factors that would decrease intra-muscle fiber expressions of
      beta- and gamma-secretases might lead to decreased production of putatively
      myotoxic oligomeric amyloid-beta42. Better understanding of the mechanisms and
      consequences of genes that predispose to sporadic inclusion-body myositis, and of
      human muscle fiber aging, could also provide new avenues toward the therapy of
      sporadic inclusion-body myositis. How to therapeutically capitalize on the new
      findings is now the challenge.

PMID- 14569206
TI  - Fibroblast and endothelial apoptosis in systemic sclerosis.
AB  - PURPOSE OF REVIEW: Systemic sclerosis is a disease characterized by vascular and
      skin changes associated with activation of fibroblasts and increased synthesis of
      matrix components. These abnormalities lead to fibrosis and impaired function of
      internal organs such as the lung, kidney, and gastrointestinal tract. Recent
      evidence suggests that although activation of cells in and around the blood
      vessels and in the skin occurs in systemic sclerosis, injury to the vascular
      endothelium and defective apoptosis of skin fibroblasts may also contribute to
      disease. The purpose of this review is to discuss these findings in the context
      of the pathophysiology of systemic sclerosis. RECENT FINDINGS: This review
      highlights concepts and recent findings relating to apoptosis of vascular
      endothelium and skin fibroblasts. Important paradigms of fibroblast cell death in
      wound healing and keloid formation are discussed. Recent observations describing
      resistance of systemic sclerosis fibroblasts to Fas-mediated apoptosis and
      activation of the antiapoptotic protein kinase, Akt, are mentioned as possible
      contributors to fibroblast selection in this disease. SUMMARY: Improved
      understanding of how death and survival signals affect vascular endothelial cells
      and skin and visceral fibroblasts will lead to new approaches to therapy.

PMID- 14569207
TI  - Evaluation and management of pulmonary hypertension in systemic sclerosis.
AB  - This review summarizes the most recent studies on pulmonary hypertension related
      to systemic sclerosis, emphasizing new insights into pathophysiology,
      identification of new markers, and advances in the diagnosis and treatment of
      this complication that greatly worsens the prognosis of patients with systemic
      sclerosis.

PMID- 14569208
TI  - Identification of novel targets in scleroderma: update on population studies,
      cDNA arrays, SNP analysis, and mutations.
AB  - PURPOSE OF REVIEW: Systemic sclerosis, or scleroderma, is an uncommon autoimmune
      connective tissue disease that results in systemic fibrosis. Its etiologic basis
      remains unclear. The pathogenesis of systemic sclerosis involves a proliferative
      and obliterative vasculopathy resulting from endothelial cell dysfunction,
      extensive fibrosis secondary to fibroblast activation, and autoimmunity as
      demonstrated by the presence of disease-specific autoantibodies. Although there
      is no clear and convincing evidence for an environmental trigger in most cases,
      accumulating data emphasize the role of genetic factors in systemic sclerosis. As
      in other complex human diseases, multiple genes likely contribute to disease
      susceptibility and the clinical manifestations of systemic sclerosis. This review
      will cover the application of genomics to the complex genetics of systemic
      sclerosis. RECENT FINDINGS: The following review is an update on novel targets
      identified in scleroderma based on published reports (May 2000-May 2003) of
      mutation/polymorphism analysis (using SNP and haplotyping), the results from a
      recent genome-wide scan on a Native American population with systemic sclerosis,
      and gene expression studies (microarrays). SUMMARY: The use of genomics has
      revealed novel targets and genetic associations that may contribute to the cause,
      the onset, and the subsequent pathologic changes that constitute systemic
      sclerosis. The identification of potential candidates for gene therapy or disease
      specific targets amenable to pharmacologic intervention will benefit patients
      with systemic sclerosis who are currently being treated for their symptoms and
      not the disease process itself.

PMID- 14569209
TI  - The role of chemokines in the pathogenesis of scleroderma.
AB  - PURPOSE OF REVIEW: The triad of pathologic changes that defines systemic
      sclerosis (scleroderma) includes immune system activation with autoimmunity; an
      obliterative, proliferative small vessel vasculopathy; and fibrosis. Available
      data suggest that several cytokines, including chemokines, contribute to the
      development of scleroderma complications. This review focuses on chemokines and
      their contribution to tissue fibrosis and pulmonary hypertension in scleroderma.
      RECENT FINDINGS: Proteins and mRNAs for monocyte chemoattractant protein-1;
      pulmonary and activation-regulated chemokine; macrophage inflammatory protein-1,
      regulated upon activation normal T cell expressed and secreted; interleukin-8;
      and transforming growth factor-beta have been found in increased amounts in blood
      or involved tissue from scleroderma patients. These factors are likely to
      contribute directly to tissue damage in scleroderma through several pathways,
      including stimulation of extracellular matrix production, induction of TGF-beta
      production and activation, and chemoattraction of T cells and nonspecific
      inflammatory cells into tissues. SUMMARY: Multiple chemokines are part of the
      pathologic network that causes tissue damage in scleroderma, and, as such, may
      provide therapeutic targets in scleroderma.

PMID- 14569210
TI  - Autoimmunity in scleroderma: the origin, pathogenetic role, and clinical
      significance of autoantibodies.
AB  - PURPOSE OF REVIEW: Systemic sclerosis, or scleroderma, is a systemic autoimmune
      disease manifest by vascular damage and fibrosis within the skin and visceral
      organs. Whereas scleroderma is a heterogenous disorder in terms of disease
      symptoms and clinical course, scleroderma-specific autoantibody profiles
      associate strongly with distinct clinical phenotypes, making serologic testing of
      great diagnostic aid. This review will focus on the clinical significance and the
      potential pathogenic role of autoantibodies in scleroderma. RECENT FINDINGS:
      Novel autoantibody and phenotype associations discovered within the past year
      underscore the clinical utility of systemic sclerosis-associated autoantibodies.
      Whereas autoantibodies are generally believed to indicate the presence of ongoing
      tissue damage, some research suggests that the humoral immune response may play a
      role in generating such damage. SUMMARY: Improvements in multiplex autoantibody
      assays will aid in the diagnosis and prognosis of the complications associated
      with systemic sclerosis. Continued research into autoantibody/phenotype
      associations could also yield critical insights into the pathogenesis of, and
      suggest novel therapeutic targets for, this chronic, debilitating disease.

PMID- 14569211
TI  - Nephrogenic fibrosing dermopathy: the first 6 years.
AB  - PURPOSE OF REVIEW: Nephrogenic fibrosing dermopathy (NFD) is a newly recognized
      scleroderma-like fibrosing skin condition. It develops in patients with renal
      insufficiency. This review summarizes recent case reports and examines theories
      of disease pathogenesis. Information from the Yale University NFD Registry
      Project, as well as published case reports, is included to provide a contextual
      framework upon which to base these theories. RECENT FINDINGS: Recent studies have
      contributed to a clearer definition of the clinical spectrum, epidemiology, and
      pathogenesis of NFD. The findings of yellow scleral plaques and circulating
      antiphospholipid antibodies have been proposed as markers of NFD in recent case
      reports. In addition, epidemiologic data have yielded several distinct clinical
      patterns of disease onset. Lastly, dual immunohistochemical staining for CD34 and
      procollagen in the spindle cells of NFD suggest that the dermal cells of NFD may
      represent circulating fibrocytes recruited to the dermis-a finding previously
      undescribed in normal skin. SUMMARY: Scenario classification of NFD is a means
      for simplifying the search for multifactorial disease triggers, and may be
      helpful in predicting prognosis and response to therapy. The technique of dual
      immunolabeling, although not yet fully characterized as a diagnostic test, may
      provide a sensitive and specific method of diagnosis, as well as a starting point
      in the investigation of other cutaneous fibrosing disorders. The postulate that
      NFD may represent a systemic disorder mediated by aberrantly functioning
      circulating fibroblast precursor fibrocytes is explored.

PMID- 14569212
TI  - Palpation for muscular tenderness in the anterior chest wall: an observer
      reliability study.
AB  - OBJECTIVE: To asses the interobserver and intraobserver reliability (in terms of
      day-to-day and hour-to-hour reliability) of palpation for muscular tenderness in
      the anterior chest wall. DESIGN: A repeated measures designs was used. SETTING:
      Department of Nuclear Medicine, Odense University Hospital, Denmark.
      PARTICIPANTS: Two experienced chiropractors examined 29 patients and 27 subjects
      in the interobserver part, and 1 of the 2 chiropractors examined 14 patients and
      15 subjects in the intraobserver studies. INTERVENTION: Palpation for muscular
      tenderness was done in 14 predetermined areas of the anterior chest wall with all
      subjects sitting. Each dimension was rated as absent or present for tenderness or
      pain for each location. All examinations were carried out according to a standard
      written procedure. RESULTS: Based on a pooled analysis of data from palpation of
      the anterior chest wall, we found kappa values of 0.22 to 0.31 for the
      interobserver reliability. For the intraobserver reliability, we found kappa
      values of 0.21 to 0.28 for the day-to-day reliability and 0.44 to 0.49 for the
      hour-to-hour reliability. CONCLUSION: Our results indicated great variations
      between experienced chiropractors palpating for intercostal tenderness or
      tenderness in the minor and major pectoral muscles in a population of patients
      with and without chest pain. This may hamper the ability of clinicians to
      diagnose and classify the musculoskeletal component of chest pain if based
      exclusively on palpation of the anterior chest wall.

PMID- 14569213
TI  - Reliability of detection of lumbar lateral shift.
AB  - BACKGROUND AND PURPOSE: The poor reliability of lateral shift detection has been
      attributed to lack of rater training, biologic variation, and test reactivity.
      This study aimed to remove the potential confounding arising from biological
      variation and test reactivity and control the level of rater experience/training
      in making judgments of lateral shift. SUBJECTS: One hundred forty-eight raters
      with 3 levels of clinical physical therapy experience and training in the
      McKenzie method participated. METHOD: The raters viewed photographic slides of 45
      patients with low back pain. Slides were judged on a numerical scale for presence
      and direction of a shift. Intrarater reliability was evaluated using the
      intraclass correlation coefficient (ICC) and interrater reliability was evaluated
      using both the ICC and kappa statistic. RESULTS: Reliability of shift judgments
      was only moderate for all groups (eg, ICC [2,1] values ranged from 0.48 to 0.64).
      CONCLUSION: Lateral shift judgements have only moderate reliability, even when
      trained raters judge stable stimuli. We propose that the photo model employed can
      be used to explore the source of error in this process.

PMID- 14569214
TI  - Subjective and Objective Numerical Outcome Measure Assessment (SONOMA). A
      combined outcome measure tool: findings on a study of reliability.
AB  - OBJECTIVE: To determine the reliability of a combined tool, namely that of
      Subjective and Objective Numerical Outcome Measure Assessment (SONOMA). METHODS:
      Testing was conducted, limited to patients with neck, midback, or lower back
      pain, with or without radiculopathy, in an outpatient chiropractic office
      setting. Test-retest reliability of the objective analysis of SONOMA was carried
      out on the same day (n = 50) with an interval time period of less than 60
      minutes. Between-day reliability of the subjective analysis of SONOMA was carried
      out with an interval time period of 24 hours (n = 50). Individual and combined
      parameter reliability was established for the tool. RESULTS: Short-term objective
      and between-day subjective reliability coefficients were high. The Pearson
      correlation coefficient for the combined tool was .96, and the coefficient for
      the individual parameters ranged from .55 through .93. All these correlations
      were statistically significant, with a P value not more than .0001. CONCLUSIONS:
      The SONOMA combined numerical outcome measure tool demonstrated a high degree of
      reliability. This outcome tool measures directly and therefore reflects patient
      pain perception, functional status, and provider-driven objective assessment. We
      believe this tool provides the unique combination of both subjective and
      objective functional capacity assessment. It should be valuable for day-to-day
      practical application, as well as considered for future clinical trials and
      quality-of-care studies. This combined tool shows promise as having a high degree
      of reliability and, hence, may demonstrate a comprehensive representation of the
      patient-clinical picture, particularly in regard to functional capacity
      assessment.

PMID- 14569215
TI  - PulStar differential compliance spinal instrument: a randomized interexaminer and
      intraexaminer reliability study.
AB  - OBJECTIVE: To provide an entry-level, new technology reliability assessment of
      the PulStar computer-assisted, differential compliance spinal instrument.
      SUBJECTS: Eighteen college students (9 male and 9 female) were recruited by
      announcements and personal contacts. METHODS: Following approval of the consent
      process by the Institutional Review Board of Mississippi State University, a
      PulStar Function Recording and Analysis System (PulStarFRAS) device was evaluated
      for clinical reliability. Two examiners, blinded from data collection, used the
      instrument on individual subjects in random order (lying prone with their backs
      exposed) to administer light impulses (approximately equal to .9 J which produced
      a 3- to 4-lb force) at each segmental level throughout the cervical, dorsal, and
      lumbar spine using probe tips spaced 3 cm apart, straddling the spinous
      processes, while a computer recorded the findings (resistance on a scale of 0 to
      25.5 lb force). Data were analyzed by Exploratory Data Analysis (EDA) with
      analysis of variance (ANOVA) testing and by use of the intraclass correlation
      coefficient (ICC). In addition, a mean test (ANOVA) was conducted to determine if
      a trend in variation occurred as a result of repeated light thrusts to the spine,
      independent of variance explained by different examiners. RESULTS: Using EDA
      analysis and ANOVA, intraexaminer reliability for the 2 practitioners was very
      high but not perfect. This was confirmed by ICC statistics demonstrating good to
      excellent reliability for both practitioners (0.89 for the experienced
      practitioner, 0.78 for the newly trained practitioner). Interexaminer reliability
      of PulStar was similarly very high but not perfect based on EDA/ANOVA analysis
      and good to excellent (ICC = 0.87). CONCLUSION: The PulStar mechanical adjusting
      device set to analysis mode appears to have good to excellent reliability when
      used by either an experienced or a novice (but trained) examiner. In addition, as
      a measure for resistance to a light thrust or spinal compliance, reliability was
      similarly good to excellent between the 2 doctors using the PulStar instrument.

PMID- 14569216
TI  - What do patients think? Results of a mixed methods pilot study assessing sciatica
      patients' interpretations of satisfaction and improvement.
AB  - BACKGROUND: Little is known about the issues low back pain patients take into
      account when deciding their satisfaction with care, the importance placed on such
      satisfaction, or the factors they consider when assessing their overall
      improvement. OBJECTIVE: The purpose of this study was to explore these issues and
      to assess the feasibility of implementing qualitative research methods within a
      clinical trial. METHODS: Study participants were volunteers taking part in a
      randomized clinical pilot study comparing nonsurgical treatments for sciatica.
      Face-to-face interviews were conducted, transcribed, and analyzed using content
      analysis. RESULTS: All 31 individuals who participated in the pilot study were
      interviewed. When asked which issues they considered when deciding their
      satisfaction with care, the most frequently identified themes were change in
      pain, personnel, and the treatment experience. When assessing their overall
      improvement, all participants considered whether their pain had changed. In
      response to the question asking participants which outcomes they considered to be
      most important, severity of pain and quality of life were most commonly cited.
      CONCLUSION: This study demonstrated that a "mixed methods" approach using
      qualitative research methods within a clinical trial is not only feasible but can
      provide interesting and useful information for trial interpretation and future
      study design. By providing insight to the multidimensional nature of patients'
      beliefs and perceptions, this technique may not only shape but also redefine the
      focus of patient-oriented research and health care for low back pain conditions.

PMID- 14569217
TI  - Chiropractic-primary care, neuromusculoskeletal care, or musculoskeletal care?
      Results of a survey of chiropractic college presidents, chiropractic organization
      leaders, and Connecticut-licensed doctors of chiropractic.
AB  - BACKGROUND: The Connecticut Chiropractic Association authorized an ad hoc
      committee to study Connecticut chiropractic scope of practice in January 1999.
      This committee was chaired by Richard Duenas, DC, and included 4 other
      Connecticut-licensed doctors of chiropractic who responded to an appeal to
      participate. OBJECTIVE: Committee members investigated the terms primary care,
      primary care provider (PCP) (clinician, physician), neuromusculoskeletal care,
      neuromusculoskeletal care provider (clinician, physician), musculoskeletal care,
      and musculoskeletal care provider (clinician, physician) to determine which, if
      any, apply to the practice of chiropractic. DATA SOURCES: A literature review was
      performed with in-depth analysis of the definitions of these terms and an
      interpretation of Connecticut Statutes for chiropractic, comparing the legal
      description of chiropractic practice to the term definitions. The literature
      review produced several detailed definitions of primary care and/or primary care
      provider (clinician, physician); however, no accurate description of
      neuromusculoskeletal (NMS) care or musculoskeletal care was found. RESULTS: Two
      opinion surveys were conducted: 1 survey included presidents of accredited
      chiropractic colleges, as well as leaders of chiropractic organizations
      throughout the world. The other survey was sent to doctors of chiropractic (DC)
      licensed in the State of Connecticut. Survey topics addressed definitions of
      primary care and PCP, the formulation of these terms, neuromusculoskeletal care
      and neuromusculoskeletal care provider, individual rights in selecting a PCP, and
      the types of practitioners considered PCPs. The consensus among chiropractic
      college presidents, organization leaders, and Connecticut-licensed doctors of
      chiropractic was that the doctor of chiropractic is qualified to provide primary
      care. Most considered any definition of primary care invalid if the chiropractic
      profession was not involved in its formulation. The overwhelming majority felt
      the patient should retain the ultimate choice in determining who should be their
      PCP. Mission statements of accredited chiropractic colleges were reviewed, paying
      particular attention to educational goals and professional qualifications of
      graduates. The committee found these institutions strive to train students in all
      aspects of primary care. CONCLUSIONS: Upon review of the literature and term
      definitions, interpretation of the statutes pertaining to chiropractic practice,
      results of both surveys, and review of the chiropractic college mission
      statements, the committee concluded that the Connecticut-licensed DC, by
      education, licensure, definition, and intraprofessional consensus, qualifies as a
      PCP.

PMID- 14569218
TI  - User's guide to the chiropractic literature-IB: how to use an article about
      therapy.

PMID- 14569219
TI  - The effects of augmented sensory feedback precision on the acquisition and
      retention of a simulated chiropractic task.

PMID- 14569220
TI  - Stroke after chiropractic manipulation as a result of extracranial postero
      inferior dissection.

PMID- 14569222
TI  - The effect of chiropractic care for a 30-year-old male with advanced ankylosing
      spondylitis: a time series case report.
AB  - BACKGROUND: Manipulative treatment for ankylosing spondylitis is a controversial
      subject, and no literature on using this therapy for advanced cases with fusion
      of the spine could be found. OBJECTIVE: To discuss the case presentation of a
      patient with advanced ankylosing spondylitis who was treated with chiropractic
      manipulation and mobilization. Clinical features The patient was a 30-year-old
      Asian male who was first diagnosed with ankylosing spondylitis at age 12. Despite
      medical intervention, a series of exacerbations had fused his sacroiliac joints
      and the facet joints in his lumbar and cervical spine. He presented with local
      moderate-to-severe pain in his low back and neck and lack of mobility.
      Intervention and outcome The patient was treated with grade 5 manipulation of his
      thoracic spine and grade 3 mobilization of his lumbar and cervical spine, along
      with physical therapy and stretches for a period of 12 weeks. He reported some
      improvement of his condition as measured by the SF-36 Health Survey and several
      measures of spinal flexibility. CONCLUSIONS: This case shows that even advanced
      cases of ankylosing spondylitis may show a favorable response to chiropractic
      manipulative therapy.

PMID- 14569223
TI  - We are the future: revisioning the faculty culture.

PMID- 14569224
TI  - We are the future: revisioning the faculty culture.

PMID- 14569226
TI  - Reflections on the continuing evolution of advanced practice nursing.

PMID- 14569228
TI  - A statewide and regional analysis of New York State nurses using the 2000
      National Sample Survey of Registered Nurses.
AB  - BACKGROUND: A national concern over the present and future workforce of
      registered nurses exists. A major initiative that would help professionals in
      workforce policy and education shorten their reaction time to surplus or shortage
      concerns is to improve the data about RNs in a given area. PURPOSE: To examine
      workforce data on New York State (NYS) nurses at the statewide and regional level
      of analysis using the 2000 National Sample Survey of Registered Nurses (NSSRN)
      Inc. METHOD: The NYS RN sample was drawn from the 2000 NSSRN by selecting the
      cases with Geocodes for NYS. This methodology yielded a sample of 1,928 NYS RNs.
      RESULTS: Data were examined in relation to RNs' demographic information,
      employment status/setting, transition/working conditions, and education.
      Consistent with national data, nurses were predominantly white, female, and in
      their mid-40s. However, important differences were found in age, minority
      representation, income, satisfaction, and work setting for NYS RNs when examining
      data at the regional and state level. DISCUSSION: Examining the 2000 NSSRN data
      at the statewide and regional level provides valid information on nursing
      workforce trends.

PMID- 14569227
TI  - Severe acute respiratory syndrome (SARS) in Hong Kong: patients' experiences.
AB  - BACKGROUND: This past year there was an outbreak of Severe Acute Respiratory
      Syndrome (SARS) in Hong Kong. During that time we investigated the clinical
      features, treatment, and nursing care of 36 patients and reported on 12 of these
      patients' perceptions of their illness experience. PURPOSE: The purpose of this
      article is to describe the clinical features, treatment, nursing care and
      perceptions of the illness experience of patients with SARS in Hong Kong in order
      to better inform nurses caring for patients with this highly contagious and
      potentially lethal disease. METHOD: We abstracted data from the medical and
      nursing records on the clinical features, treatment and nursing care of 36
      patients (21 women, 15 men) in whom SARS was diagnosed and who were admitted to
      the Queen Mary Hospital in Hong Kong between March 15 and April 15, 2003. A
      review of the hospital's policy and procedures on infection control was also
      undertaken. Semi-structured interviews were conducted with 12 of the patients to
      elicit their perceptions of the illness experience. FINDINGS: The most common
      symptoms were cough (83%), dyspnea (80.6%), malaise (69.4%) and fever (61%). Less
      common symptoms included headache (38.9%), diarrhea (38.9%), dizziness (30.6%),
      myalgia (25%), chills (19.4%), nausea and vomiting (19.4%) and rigor (the
      occurrence of a sensation of hot-and-cold and shivering in addition to teeth
      chattering and bed shaking) (8.3%). All 36 patients received a combination of
      corticosteroids and ribavirin. The patients were at risk of drug-related adverse
      reactions and deterioration of respiratory function, and nursing vigilance was
      required. CONCLUSION: Nursing patients with SARS was challenging as the disease
      was highly contagious and potentially lethal, and not much was known about this
      disease. In addition to the use of frontline treatment, infection control and
      sensitivity to individual responses to sudden and catastrophic illness were
      required to support these patients. From this outbreak of SARS, we have learned
      the importance of infection control in containing and controlling the disease.
      Other lessons included the need to strengthen the surge capacity in our hospitals
      and support health care workers during the crisis.

PMID- 14569229
TI  - Determining nursing faculty development needs.
AB  - Although faculty members often come to a university school of nursing with little
      or no experience in teaching, research, or other forms of scholarship, few
      schools of nursing have a comprehensive, formalized faculty development program.
      In considering the need to find and retain the best faculty in this competitive
      market, the University of North Carolina at Chapel Hill School of Nursing
      appointed a task force to develop a formal faculty development program for the
      School. After reviewing the literature and contacting 24 schools of nursing, the
      task force concluded that most do not offer a systematic approach to faculty
      development. The task force developed and distributed a needs assessment and
      received responses from 53% of the faculty. Based on the needs assessment the
      task force made eight recommendations to the faculty for an ongoing,
      comprehensive faculty development program.

PMID- 14569230
TI  - Orality to literacy: effects on nursing knowledge.
AB  - BACKGROUND: Around the time of Plato and Aristotle, writing was introduced into
      the Western world and caused an epistemological revolution. Academics describe
      this change from pre-literacy to literacy as the alphabetization of a society. If
      societies have no written alphabet or words, knowledge transmission is oral.
      Words and ideas are fluid because they are always particularized to specific
      situations, rather than being written and available for scrutiny. With
      alphabetization, people record events, experiences and exchanges. Meanings no
      longer change slightly with each telling because writing solidifies knowledge as
      people attach increasingly limited meanings to words. Nursing experienced a
      similar revolution from orality to literacy with the proliferation of nursing
      journals beginning in the 1970's. Consequently, nurses and nurse educators also
      experienced an epistemological revolution resulting in knowledge from literacy
      usually being automatically valued higher than knowledge from orality. PURPOSE: I
      critically examine changes to knowledge that nurse educators value as a result of
      an alphabetized discipline. DISCUSSION: By comparing epistemological changes
      resulting from alphabetization in ancient Greece with similar changes in nursing
      education, I discuss three important dynamics: the sedimentation of words, the
      growth of criticism, and the new rationality. CONCLUSION: Some epistemological
      changes resulting from literacy are positive for nursing (eg, the growth of
      criticism) while some changes are negative (eg, devaluing sensorial and
      experiential knowledge).

PMID- 14569231
TI  - Scientific integrity: a review of the Institute of Medicine's (IOM) reports.

PMID- 14569232
TI  - Resources in research ethics.

PMID- 14569233
TI  - American Academy of Nursing News.

PMID- 14569234
TI  - The National Health Policy Forum (NHPF): an organization nurses need to know.

PMID- 14569235
TI  - American Academy of Nursing: Interim report of the Task Force on Health
      Disparities. July 2003.

PMID- 14569237
TI  - Exercise training improves insulin-stimulated myocardial glucose uptake in
      patients with dilated cardiomyopathy.
AB  - BACKGROUND: The effects of exercise training on myocardial substrate utilization
      have not previously been studied in patients with idiopathic dilated
      cardiomyopathy and mild heart failure. METHODS AND RESULTS: Myocardial glucose
      uptake was studied in 15 clinically stable patients with dilated cardiomyopathy
      (New York Heart Association class I-II, ejection fraction 34% +/- 8%) with the
      use of 2-[fluorine 18]fluoro-2-deoxy-d-glucose ([F-18]FDG) and positron emission
      tomography under euglycemic hyperinsulinemia. Eight of these patients
      participated in a 5-month endurance and strength training program, whereas seven
      patients served as nontrained subjects. Left ventricular function was assessed by
      2-dimensional echocardiography before and after the intervention. After the
      training period, insulin-stimulated myocardial fractional [F-18]FDG uptake and
      glucose uptake rates were significantly increased in the anterior, lateral, and
      septal walls (P <.01) in the trained subjects but remained unchanged in the
      nontrained subjects. In the trained patients, whole-body insulin-stimulated
      glucose uptake was enhanced and serum free fatty acid levels were suppressed
      during hyperinsulinemia compared with the baseline study (P <.05). No changes
      were observed in the nontrained group. CONCLUSIONS: These results indicate that
      exercise training in patients with dilated cardiomyopathy improves insulin
      stimulated myocardial glucose uptake. This improvement in glucose uptake may be
      indicative of a switch in myocardial preference to a more energy-efficient
      substrate.

PMID- 14569238
TI  - Stress-related variations in left ventricular function as assessed with gated
      myocardial perfusion SPECT.
AB  - BACKGROUND: There is inconsistency in reported patient characteristics associated
      with differences in basal and poststress left ventricular function (delta
      ejection fraction [DeltaEF]) assessed by gated single photon emission computed
      tomography (SPECT). This inconsistency may therefore hamper adequate
      interpretation. In this study we first determined the reproducibility of serial
      gated SPECT-assessed left ventricular function. Second, we determined whether
      left ventricular ejection fraction (LVEF) assessed directly after stress reflects
      basal LVEF and, if not, what patient characteristics were associated with this
      discrepancy in LVEF. METHODS AND RESULTS: Serial reproducibility of technetium
      99m tetrofosmin gated SPECT-assessed LVEF in 22 patients showed a mean difference
      between two sequential measurements at rest of 0.09% EF units, with a 95% limit
      of agreement (2 SDs) at 5.8% EF units. In 229 patients Tc-99m tetrofosmin gated
      SPECT was performed after stress and at rest. Independent predictors of DeltaEF
      were the presence of scintigraphically proven ischemia (standardized coefficient,
      -1.256; P =.003) and difference in heart rate at the time of acquisition
      (standardized coefficient, 0.121; P =.001). CONCLUSIONS: Gated SPECT-assessed
      LVEF at rest is reproducible under standard clinical conditions. However, LVEF
      assessed after stress does not represent LVEF at rest in patients with
      scintigraphically proven ischemia and in patients with increased heart rate after
      stress compared with heart rate at rest.

PMID- 14569239
TI  - Perioperative and long-term prognostic value of dipyridamole Tc-99m sestamibi
      myocardial tomography in patients evaluated for elective vascular surgery.
AB  - BACKGROUND: Patients with peripheral vascular disease are at increased risk for
      perioperative and long-term cardiac morbidity and mortality. Substantial data
      exist supporting the use of preoperative clinical risk stratification and planar
      thallium myocardial scintigraphy. Only limited data are available assessing the
      role of technetium-99m (Tc-99m) single photon emission computed tomography
      (SPECT) for preoperative evaluation in this population. METHODS AND RESULTS: In
      our study 153 patients who underwent peripheral vascular surgery were followed up
      for up to 4 years after preoperative dipyridamole Tc-99m sestamibi SPECT to
      determine clinical and SPECT predictors of perioperative and long-term adverse
      cardiac events by multivariate analysis. There were no statistically significant
      clinical or SPECT predictors of perioperative risk, although no perioperative
      events occurred in patients with normal scans. Abnormality in the left anterior
      descending (LAD) territory (risk ratio = 3.1; 95% confidence interval, 1.4-7.1)
      was the only statistically significant univariate predictor of long-term death or
      myocardial infarction. Only abnormality in the LAD territory appeared to improve
      model fit beyond clinical risk (risk ratio = 2.9; 95% confidence interval, 1.2
      7.3; P =.02). CONCLUSIONS: Patients with normal preoperative scans have a low
      risk of perioperative cardiac events and may safely undergo peripheral vascular
      surgery without further coronary intervention. However, scan abnormality in the
      LAD distribution confers poor long-term prognosis, suggesting that patients with
      this finding before peripheral vascular surgery should receive aggressive medical
      therapy and possibly invasive intervention to improve long-term survival.

PMID- 14569241
TI  - The measurement of extravascular lung density with SPECT imaging and its
      relationship with ventilatory abnormalities in patients with congestive heart
      failure.
AB  - BACKGROUND: Patients with congestive heart failure (CHF) have increased
      ventilatory equivalent for carbon dioxide (Ve/VCO(2)), which may contribute to
      the symptom of exercise-induced hyperpnea. We have developed a technique in which
      simultaneous blood volume single photon emission computed tomography imaging and
      transmission tomography are used to measure extravascular lung density (ELD). We
      investigated the correlation between Ve/VCO(2) and ELD in patients with CHF.
      METHODS AND RESULTS: Thirteen patients with stable CHF and eleven control
      subjects were studied. Attenuation-corrected blood volume emission tomography was
      acquired with simultaneous transmission tomography to measure pulmonary blood
      volume and total lung density, respectively. Seven CHF patients underwent maximal
      exercise treadmill testing with online respiratory gas analysis. ELD was
      calculated as total lung density minus pulmonary blood volume. SPECT and
      transmission tomography were repeated immediately after exercise. CHF patients
      had significantly higher total lung density and ELD compared with normal
      subjects. No differences in pulmonary blood volume were observed. There was a
      significant inverse correlation between ELD and left ventricular ejection
      fraction at rest in CHF patients (r = -0.77, P <.001). A strong correlation was
      also found between post-exercise ELD and Ve/VCO(2) at peak exercise (r = 0.74, P
      =.008) and at anaerobic threshold (r = 0.67, P =.024). CONCLUSION: Patients with
      chronic CHF have increased ELD. The correlation between ELD and Ve/VCO(2)
      suggests that increased lung water may contribute to the ventilatory
      abnormalities seen in patients with CHF.

PMID- 14569240
TI  - Selective intracoronary injection of sestamibi to detect myocardial viability:
      Prediction of perfusion and contractile recovery after percutaneous transluminal
      coronary angioplasty.
AB  - BACKGROUND: The main limitation of myocardial single photon emission computed
      tomography (SPECT) in detecting hibernating myocardium is the poor delivery of
      radiotracers in hypoperfused areas supplied by severely stenotic coronary
      arteries. Increasing local availability of radiotracers by intracoronary
      injection might represent an attractive solution. The hypothesis that the
      intracoronary administration of sestamibi could improve myocardial SPECT accuracy
      in detecting hibernating myocardium was addressed in this pilot study. METHODS
      AND RESULTS: Seven patients with prior myocardial infarction and severe stenosis
      of the infarct-related artery underwent myocardial SPECT after intracoronary
      injection of technetium 99m sestamibi immediately before percutaneous
      transluminal coronary angioplasty (PTCA). Wall motion and perfusion were
      evaluated, before and 1 month after PTCA, by 2-dimensional echocardiography and
      rest-redistribution thallium 201 SPECT. A "low-flow area" was identified on the
      pre-PTCA Tl-201 SPECT image as the area with less than 50% of maximum radiotracer
      uptake. Changes in wall motion and perfusion in the low-flow area were compared
      with results of intracoronary sestamibi imaging. On a pixel-by-pixel analysis,
      intracoronary sestamibi predicted perfusion recovery within the low-flow area
      with a 91% sensitivity, a 78% specificity, and an 82% overall accuracy. Only in
      the 5 patients with an extent of sestamibi uptake greater than one third of the
      low-flow area was an improved regional and global left ventricular wall motion
      observed after PTCA (wall motion score index decreased from 1.95 +/- 0.28 to 1.60
      +/- 0.34, P =.007; left ventricular ejection fraction increased from 42% +/- 7%
      to 49% +/- 7%, P =.001; asynergic segments in the low-flow area decreased from
      3.6 +/- 0.9 to 1.8 +/- 1.5, P =.021). CONCLUSIONS: In patients with prior
      myocardial infarction and severe stenosis of the infarct-related artery,
      sestamibi uptake after intracoronary administration identified viable myocardium
      that was undetected after rest-redistribution thallium SPECT but capable of
      clinically significant contractile improvement after revascularization.

PMID- 14569242
TI  - Esophageal dysfunction in patients with atypical chest pain investigated with
      esophageal scintigraphy and myocardial perfusion imaging: an outcome study.
AB  - BACKGROUND: The objectives of this study were to determine the role of esophageal
      scintigraphy (ES) and myocardial perfusion imaging (MPI) in patients with
      atypical chest pain investigated for ischemic heart disease (IHD). METHODS AND
      RESULTS: One hundred five consecutive patients with atypical chest pain were
      investigated by dual-isotope MPI (1-day rest-stress protocol). Within a 10-day
      period, each patient also had liquid and semisolid ES performed with dynamic
      imaging over a 2-minute period for each phase. All patients were risk-stratified,
      and 28 patients were also investigated by coronary angiography. Patient outcome
      was assessed with the use of endpoints including cardiac death, myocardial
      infarction, and coronary revascularization procedures. Of the patients, 53 (50%)
      had esophageal dysfunction (ED) but no IHD, 41 (39%) had both ED and IHD, 5 (5%)
      had normal ES and IHD, and 6 (6%) had neither ED nor IHD. On the basis of outcome
      findings (n = 105) and coronary angiogram results (n = 28), MPI showed
      sensitivity for the detection of IHD of 92% in this patient population. Of the 94
      patients (89%) with ED, 48 (51%) showed esophageal dysmotility, 9 (10%) showed
      gastroesophageal reflux, 17 (18%) showed esophageal spasm and dysmotility, 17
      (18%) showed both reflux and dysmotility, and 3 showed other abnormalities. The
      median follow-up period after MPI was 20 months (range, 9-30 months). Twenty-one
      patients had cardiac events. These included 2 cardiac deaths, 2 myocardial
      infarctions, 6 coronary artery bypass graft surgeries, and 11 angioplasty/stent
      procedures. All but 2 of these patients had abnormal ES studies, and 7 had no
      prior history of IHD. MPI detected IHD in all but 2 of these patients.
      CONCLUSIONS: There is a high incidence of ED in patients with atypical chest pain
      referred for cardiologic assessment. The low proportion of patients with IHD
      alone and of those with neither IHD nor ED presenting with atypical chest pain
      (5%), as well as the high proportion with ED alone (50%), indicates the high
      likelihood of chest pain derived from ED. However, of the 21 patients with
      cardiac events, 7 had no prior history of IHD, indicating the importance of the
      use of MPI in the investigation of patients with atypical chest pain syndromes.

PMID- 14569243
TI  - Abnormal heart rate recovery immediately after treadmill testing: correlation
      with clinical, exercise testing, and myocardial perfusion parameters.
AB  - BACKGROUND: The increase in heart rate during exercise is considered to be
      attributed to sympathetic system activation combined with parasympathetic
      withdrawal. The prognostic importance of the chronotropic response to exercise
      and heart rate recovery 1 minute after exercise has already been established. The
      purpose of this study was to evaluate heart rate recovery as an index of
      myocardial ischemia, by correlating heart rate recovery with known parameters of
      myocardial ischemia. METHODS AND RESULTS: Included in the study were 304
      consecutive patients (73% men), aged 34 to 82 years. Patients whose heart rate
      recovery value or myocardial perfusion imaging could have been influenced by
      factors other than ischemic disease were excluded from the study. The patients
      underwent single photon emission computed tomography myocardial perfusion imaging
      combined with symptom-limited exercise testing with thallium 201 or technetium
      99m tetrofosmin. The value for heart rate recovery was defined as the decrease in
      heart rate from peak exercise to 1 minute after termination of exercise. For
      semiquantitation of the scintigram, the uptake of the radiotracer was graded on a
      scale from 0 to 4. Twenty-one beats per minute was defined as the lowest normal
      value for heart rate recovery. We found 74 patients (24%) with an abnormal value.
      We also found a significant correlation between heart rate recovery 1 minute
      after exercise and stress myocardial perfusion score. In addition, there was a
      statistically significant relationship between heart rate recovery and
      chronotropic variables. Patients with an abnormal value of heart rate recovery
      were generally of an older age, were more likely men, had a higher frequency of
      risk factors for coronary artery disease, were mostly taking cardioactive
      medications, had lower efficiency during treadmill testing, and had more
      pathologic findings on the scintigram. CONCLUSIONS: Myocardial ischemia, as
      assessed by myocardial perfusion imaging, is an important correlate of heart rate
      recovery. There is a significant correlation between chronotropic variables
      during exercise testing and heart rate recovery 1 minute after exercise. It seems
      that the heart rate recovery value 1 minute after peak exercise may be considered
      a reliable index of the severity of myocardial ischemia.

PMID- 14569244
TI  - Resting "Solar Polar" map pattern and reduced apical flow reserve:
      characteristics of apical hypertrophic cardiomyopathy on SPECT myocardial
      perfusion imaging.
AB  - BACKGROUND: Patients with apical hypertrophic cardiomyopathy (ACM) are often
      referred for myocardial perfusion single photon emission computed tomography
      (SPECT) as a result of marked T-wave inversion and chest pain syndromes. Stress
      perfusion defects have been reported in ACM, but the characteristic SPECT pattern
      as well as the typical findings on volume-weighted polar maps has not been
      described. METHODS AND RESULTS: Dual-isotope rest (thallium 201) and exercise or
      adenosine stress (technetium 99m tetrofosmin) myocardial perfusion SPECT was
      performed in 11 patients with ACM, including 8 with either normal coronary
      arteriography (n = 5) or a low pretest probability of coronary artery disease
      (CAD) (n = 3), and 14 control patients with concentric left ventricular
      hypertrophy. An 8-pixel-diameter circular region of interest was used to
      quantitatively compare apical and septal counts on CEqual volume-weighted polar
      maps. A characteristic "Solar Polar" map pattern resulting from the increased
      apical counts was present in each ACM patient at rest, with a mean apical-septal
      ratio of 1.39 +/- 0.17 (range, 1.23-1.62, P <.01 vs concentric left ventricular
      hypertrophy group). With stress, there was a significant decrease in the apical
      septal ratio (0.96 +/- 0.18, P <.001 vs rest) in the ACM subgroup without CAD.
      CONCLUSION: Patients with ACM demonstrate a newly described "Solar Polar" map
      pattern at rest, as well as relative apical ischemia on the stress images even in
      the absence of CAD.

PMID- 14569245
TI  - PET imaging in small animals.

PMID- 14569246
TI  - Acute cardiovascular response to exercise and its implications for exercise
      testing.

PMID- 14569247
TI  - First annual Mario S. Verani, MD, Memorial lecture: clinical value of myocardial
      perfusion imaging in coronary artery disease.
AB  - I am honored to give this lecture in memory of Dr Mario S. Verani, a friend and a
      respected colleague in the field of nuclear cardiology. Dr Verani made many
      immense contributions to the field of nuclear cardiology during his lifetime. He
      was a pioneer in the field of pharmacologic stress imaging and played a leading
      role in validating the utility of intravenous adenosine infusion for stress
      imaging in detecting significant coronary stenoses and assessing prognosis. He
      and his colleagues at Baylor reported that pharmacologic stress imaging could
      separate high- and low-risk patient subsets after acute myocardial infarction,
      particularly among patients who underwent thrombolytic therapy. He informed us
      that certain drugs that patients took could influence perfusion defect severity.
      This work led to a clinical study showing that ischemic defect size could be
      substantially reduced with medical therapy in patients who had recently had an
      acute infarction. An outcome of this observation was the launching of the INSPIRE
      (adenosINe technetium-99m Sestamibi single-photon emission computed tomography
      Post-InfaRction Evaluation) trial in which postinfarction patients are randomized
      to medical therapy or revascularization. Dr Verani was an able debater when
      assigned the position for advocating for stress radionuclide perfusion imaging
      against stress echocardiography. He engaged in these debates with substantial
      knowledge but always with a touch of humor. Dr Verani's courage was an
      inspiration to all of us during his illness. His legacy as a pioneer will endure
      as the field of nuclear cardiology continues to mature and expand.

PMID- 14569248
TI  - PET myocardial glucose metabolism and perfusion imaging: Part 1-Guidelines for
      data acquisition and patient preparation.

PMID- 14569250
TI  - Correct interpretation of a myocardial perfusion SPECT study in a patient with
      Ebstein's anomaly through recognition of septal artifact.

PMID- 14569249
TI  - PET myocardial perfusion and glucose metabolism imaging: Part 2-Guidelines for
      interpretation and reporting.

PMID- 14569251
TI  - Increased right ventricular activity: artifact of camera head misalignment.

PMID- 14569256
TI  - Stress response and optimization of perioperative care.

PMID- 14569259
TI  - Improved biological and transcriptional activity of monopegylated interferon
      alpha-2a isomers.
AB  - The addition of polyethyleneglycol (PEG) side chains to interferon alpha-2a
      improves the serum stability and clinical efficacy. Current commercial PEG-INF
      formulations such as PEGASYS are heterogeneous and contain multiple monopegylated
      isomers. We have analyzed the activity of nine, purified monopegylated variants
      in antiproliferative, antiviral and binding assays, together with a global
      transcriptional analysis using DNA oligonucleotide microarrays. We show a direct
      correlation between biological and transcriptional activity for all isomers and
      an inversed correlation between IFN-receptor 2a affinity and signal transduction.
      Two out of nine positional isomers have a higher specific biological and
      transcriptional activity than the mixture, which can be explained by unique
      structural features of interferon signaling, which involves two distinct
      receptors. The possible clinical implications are discussed, which might guide
      the development of pegylated interferons with improved pharmacological
      properties.

PMID- 14569258
TI  - Gender-specific contribution of the GABA(A) subunit genes on 5q33 in
      methamphetamine use disorder.
AB  - Family and twins studies have suggested that genetic factors are involved in the
      development of substance use disorders. Several unrelated case/control
      association studies have reported associations of the GABA(A) subunit genes on
      5q33 with the development of alcohol dependence. We hypothesized that these
      particular GABA(A) subunit genes also contribute to the development of
      methamphetamine use disorder. To test our hypothesis, we recruited cases using a
      series of questionnaires. Among the polymorphic SNPs, significant differences
      between cases and controls were identified in the female sample in the rs2279020
      of the GABA(A)alpha1 subunit gene, and the novel SNP rs4480617 in the
      GABA(A)gamma2 subunit gene. No associations were found in the male sample.
      Further haplotype analysis identified several marker blocks significantly
      associated with methamphetamine use disorder in females; each block consists of
      the rs4480617. Our study provides preliminary evidence that the GABA(A) subunit
      genes on 5q33 may preferentially contribute to methamphetamine use disorder in
      females.

PMID- 14569260
TI  - Mobility of the spine after spinal surgery in acute spinal cord injury.
AB  - STUDY DESIGN: Retrospective study of mobility of the spine. OBJECTIVES: To study
      the relation between mobility of the spine, operation and length of surgical
      stabilisation. SETTING: The National Spinal Injuries Centre, Stoke Mandeville
      Hospital, Aylesbury, UK. METHOD: Questionnaires were sent to 99 consecutive acute
      traumatic spinal cord-injured patients (UK residents) admitted in 1990-1994. All
      had acute spinal surgery. A total of 68 responded. Their replies, medical records
      and radiographs were reviewed. RESULTS: (1) In all, 63 patients had surgery in
      the cervical, thoracolumbar or lumbar spine; 11 of them had more than two
      functional spinal units (FSUs) stabilised, 10 of these 11 (91%) had less than
      satisfactory results in terms of metal failure, improper placement of the implant
      or functional restriction of spinal mobility (FROSM). A total of 35 had 1-2 FSUs
      stabilised. None of them had metal failure or improper placement of implant, but
      14 (40%) had less than satisfactory result due to FROSM; 17 had laminectomy
      alone, four of these had FROSM. (2) Five patients had surgery in the thoracic
      spine. Three of these who had 5-7 FSUs stabilised had no FROSM. Two had
      laminectomy alone, one of whom had FROSM. CONCLUSION: (1) Long surgical
      stabilisation in the cervical, thoracolumbar and lumbar spines was likely to
      result in either metal failure or FROSM. (2) Long surgical stabilisation of the
      thoracic spine was not associated with either metal failure or FROSM. (3) A small
      proportion of patients had laminectomy alone. One of them who had multiple
      injuries had FROSM.

PMID- 14569261
TI  - Types and effectiveness of treatments used by people with chronic pain associated
      with spinal cord injuries: influence of pain and psychosocial characteristics.
AB  - STUDY DESIGN: Postal survey. OBJECTIVES: Because of the high prevalence and
      inadequate control of pain following spinal cord injury (SCI), it is important to
      have information about the factors associated with the use of specific pain
      therapies. We conducted this study to evaluate the ability of pain
      characteristics and psychosocial factors to predict the use of treatments.
      SETTING: The Miami Project to Cure Paralysis (Miami, FL, USA). METHODS: People
      with SCI (n=120) were mailed a packet containing a questionnaire with questions
      regarding demographic factors, pain characteristics, and pain treatments along
      with a copy of the Multidimensional Pain Inventory. RESULTS: A total of 59% of
      the respondents had been prescribed treatment or self-initiated efforts to treat
      pain over the previous 18-month period. The most common treatments used by this
      sample were massage (26.6%), opioids (22.5%) and nonsteroidal anti-inflammatory
      drugs (NSAIDs) (20%). The most effective treatments overall were 'physical
      therapies' with 50% receiving these treatments indicating that their pain was
      'considerably reduced' or that they were 'pain free.' Opioids and anticonvulsants
      were perceived to be the most effective pharmacological agents prescribed (33.3
      and 23.8% reporting their pain was considerably better or eliminated,
      respectively). People using prescription medication reported significantly
      greater pain severity, more widespread pain, more descriptive adjectives, more
      evoked pain, greater difficulty in dealing with pain, and more interference and
      decreased activity levels due to pain, compared to people not using prescription
      medication. A combination of greater difficulty in dealing with pain, intense
      pain, presence of evoked pain, and higher level of perceived support from
      significant others was predictive of taking prescription medication. CONCLUSION:
      People taking prescription medication reported significantly more intense pain
      with neuropathic characteristics that significantly affected daily life and
      routine activities. A substantial percentage of individuals with pain related to
      SCI did not obtain significant pain relief from prescription medications. None of
      the factors assessed predicted the use of nonprescription treatments. The results
      of this study confirm the inadequacy of available modalities to manage chronic
      pain related to SCI.

PMID- 14569262
TI  - Inhibition of monocyte/endothelial cell interactions and monocyte adhesion
      molecule expression by the immunosuppressant mycophenolate mofetil.
AB  - STUDY DESIGN: In vitro study on the effects of mycophenolate mofetil (MMF) on
      isolated human monocytes and endothelial cells. OBJECTIVES: Haematogenous
      macrophages play an essential role in the development of secondary damage
      following spinal cord injury (SCI), and there is evidence that the use of
      immunosuppressants such as MMF can reduce monocyte invasion and neuronal damage.
      SETTING: University Hospital for Orthopaedic Surgery, Frankfurt am Main, Germany.
      METHODS: The effects of MMF on the adhesion of human monocytes to human umbilical
      vein endothelial cells (HUVEC), monocyte binding to immobilised E-selectin, and
      monocyte expression of intercellular adhesion molecule (ICAM)-1, sialyl Lewis X
      (sLeX) and major histocompatibility complex (MHC)-II were studied. The binding of
      monocytes to E-selectin was examined by using purified and immobilised E-selectin
      fusion protein. Adhesion molecule expression was investigated by flow cytometry.
      RESULTS: The binding of monocytes to HUVEC was significantly reduced by 30.1%
      after treatment of monocytes with MMF (10 microg/ml), whereas the pretreatment of
      HUVEC with MMF did not result in significant changes in monocyte adhesion. MMF
      forcefully inhibited monocyte binding to immobilised E-selectin by 55.7%.
      Furthermore, MMF significantly inhibited the upregulation of ICAM-1- and MHC-II
      expression on monocytes stimulated with either lipopolysaccharide or interferon
      gamma, whereas the expression of sLeX was not impaired. Toxic effects were
      excluded by propidium-iodide staining and measurement of fluorescein-diacetate
      metabolism. CONCLUSION: MMF can downregulate important monocytic adhesion
      molecules and inhibits monocyte adhesion to endothelial cells, thus indicating
      that treatment with MMF could be beneficial after SCI. SPONSORSHIP: This study
      was supported by the DFG (Ha 2721/1-3), the Paul und Ursula Klein-Stiftung and
      the Stiftung Friedrichsheim.

PMID- 14569264
TI  - Complications during the acute phase of traumatic spinal cord lesions.
AB  - STUDY DESIGN: Prospective 2 years survey from 1 February 1997 to 31 January 1999.
      OBJECTIVES: To assess the incidence of complications during the acute stage of
      spinal cord lesions and the possible correlations between them and the type of
      care and rehabilitation provided. SETTING: Spinal cord injured patients
      consecutively admitted to 37 Italian Rehabilitation Centres (RCs). METHODS: The
      study population was drawn from the GISEM (Italian Group for the Epidemiological
      Study of Spinal Cord Injuries) study (1997-1999), which involved the
      participation of 37 RCs and Spinal Units (SUs), situated all over Italy, mainly
      in the northern and central part of the country. Only patients admitted within 60
      days from the traumatic injury were considered. This yielded a population of 588
      patients (18% females and 82% males). Six of the most common complications were
      considered: trophic skin changes, heterotopic ossifications, urinary
      complications, respiratory complications, deep-vein thrombosis and pulmonary
      embolism. RESULTS: Results revealed a high incidence of trophic skin changes
      (23.3%), while over half of the patients presented at least one of the
      complications under examination. Trophic skin changes occurred exclusively among
      the patients whose admission to the SUs had been delayed or who had received
      initial treatment in nonspecialised Centres. CONCLUSIONS: Optimal rehabilitation
      care, with regard to the prevention of complications during the acute phase,
      entails early admission to a specialised multidisciplinary facility, namely an
      SU.

PMID- 14569263
TI  - Spinal cord lesion management in Italy: a 2-year survey.
AB  - DESIGN: Prospective 2-year survey from 1 February 1997 to 31 January 1999.
      OBJECTIVES: To compare the route from injury to rehabilitation, and the outcome
      of care in a large sample of traumatic (T) and nontraumatic (NT) spinal cord
      lesion (SCL) patients at their 'first admission'. SETTING: T and NT SCI patients
      consecutively admitted to 37 SCL centres in Italy. METHOD: Data were recorded on
      simple, computerised, closed-question forms, which were Centrally collected and
      analysed. Descriptive and inferential analysis was conducted to define the
      characteristics and compare the T and NT populations, and to identify
      correlations among the variables examined: time from the event to admission
      (TEA); pressure sores (PS) on admission; length of stay (LoS) and destination on
      discharge. RESULTS: A total of 1014 SCL patients, 67.5% with a lesion of T and
      32.5% of NT aetiology were analysed. The subjects in the T group were younger
      (median 34 versus 58 years), with higher probability of cervical involvement (OR
      2.47, CI 1.8-3.4) and completeness of the lesion (OR 3.0, CI 2.3-4.0), shorter
      median TEA (37 versus 64 days, P<0.0001) and less frequent admission from home
      (3.6 versus 17.4%) compared to the NT group. TEA and PS on admission were
      analysed as indicators of the efficacy of the courses from injury to
      rehabilitation. Longer TEA was reported for people with NT aetiology, admitted to
      rehabilitation centre (RC), not locally resident, transferred from certain wards
      and to a lesser degree female subjects and those with complications on admission.
      PS were associated to completeness of lesion, longer TEA, admission to RC,
      nonlocal residence and coming from general intensive care units, or general
      surgery wards. Median LoS was 99 days (mean 116 and range 0-672), and was
      statistically shorter in the NT group (122 versus 57 median, P<0.00001). Upon
      discharge, bladder and bowel autonomy were, respectively, obtained in 68.1 and
      64.5% of the whole population without significant difference between the T and NT
      groups. A total of 80.2% of patients were discharged home and the following
      factors: not living alone, being discharged after longer LoS, having sphincterial
      autonomy and no PS, were all independent predictors of outcome. CONCLUSION: There
      are important obstacles in the admission route to rehabilitation facilities,
      greater for NT, as longer TEA and more complications on admission testify.
      Moreover, the LoS is shorter for NT population. Our findings suggest that
      rehabilitation outcome could be improved through an early multidisciplinary
      approach and better continuity between acute and rehabilitation care, especially
      for the 'neglected' NT SCL patients.

PMID- 14569265
TI  - Removal of the tracheostomy tube in the aspirating spinal cord-injured patient.
AB  - STUDY DESIGN: Four related case reports, occurring within a 10-month time frame
      during 2001. OBJECTIVES: Aspiration is commonly reported in the literature as a
      contraindication to decannulation. We report four examples of successful removal
      of the tracheostomy tube in the presence of aspiration by an experienced team,
      utilising a risk management approach. SETTING: Victorian Spinal Cord Service
      (VSCS), Austin Hospital, Melbourne, Australia. METHODS: Four individuals in our
      unit with traumatic spinal cord injury, three quadriplegic and one paraplegic,
      presented with aspiration identified by a positive modified Evan's blue dye test
      or constant coughing, gagging and oxygen desaturation during cuff deflation
      trials. In three of the four cases, the tracheostomy tube had been in situ for a
      prolonged period and the patients had failed to progress towards decannulation. A
      decision was made to decannulate these four patients in spite of the presence of
      traditionally held contraindications for decannulation. The multidisciplinary
      team carefully compared the inherent risks of premature decannulation against
      those of prolonged tracheostomisation. Given the risk associated with this
      procedure, a closely monitored decannulation protocol was instituted. RESULTS:
      All four patients were successfully decannulated with improved quality of life,
      eating between 1 and 4 days and communicating immediately after decannulation.
      None experienced respiratory deterioration. CONCLUSION: It is possible to safely
      decannulate aspirating spinal cord injured individuals in some instances, using a
      risk management approach.

PMID- 14569266
TI  - Penile erosion in spinal cord injury--an important lesson.
AB  - STUDY DESIGN: A case report of the complications of a spinal cord injury (SCI)
      patient alternating between indwelling urethral catheter and a condom drainage
      system for bladder management. OBJECTIVE: To highlight the importance of penile
      care for bladder drainage following SCI. SETTING: Spinal Injuries Unit, Stanmore,
      UK. SUBJECT: A 39-year-old male who sustained a lumbar level SCI in December
      2000. He presented acutely with leakage of urine around his condom drainage
      device. MAIN OUTCOME MEASURE: The examination revealed an eroded area on the
      ventral aspect of the proximal penile shaft, which corresponded to the site of
      condom attachment. An indwelling urethral catheter was inserted as a temporary
      measure before reconstruction. RESULT: At operation, in addition to the
      preoperatively observed area of erosion, the penile urethra was found to be
      cleaved for almost its entire length. CONCLUSIONS: The patient had suffered two
      complications from a combination of two types of bladder management, and surgery
      was successful in treating both the urethral cleavage and the skin erosion.

PMID- 14569267
TI  - Intramedullary epidermoid cyst presenting with abnormal urological
      manifestations.
AB  - STUDY DESIGN: Report of an epidermoid cyst with intramedullary localization.
      OBJECTIVE: To describe an atypical presentation of intramedullary epidermoid
      cyst. SUMMARY OF BACKGROUND DATA: Intramedullary epidermoid cysts are rare
      entities with a marked variability in the clinical presentation, essentially of
      neurological pertinence. METHODS: Case report of a spinal epidermoid cyst in a 13
      year-old girl presenting with urological symptoms: she had a 12-month history of
      recurrent low urinary tract infections, urinary frequency and nocturnal enuresis.
      A urodynamic evaluation was performed and showed the presence of involuntary
      bladder contractions with detrusor instability and low bladder compliance.
      Magnetic resonance imaging of the spine demonstrated an intramedullary lesion of
      the dorsal spinal cord. RESULTS: The mass was excised and 6 months after surgical
      excision, urological manifestations improved with decreased detrusor hyper
      reflexia, increased bladder capacity and compliance and no later report of
      urinary tract infections. CONCLUSIONS: In our patient, unusual clinical
      manifestations of the tumor have delayed the diagnosis, but its complete removal
      has led to remission of symptoms. Detailed neurological examination and
      investigations are indicated in patients with clinical and urodynamic features,
      suggestive of neuropathic bladder.

PMID- 14569268
TI  - Spinal subarachnoid hematoma compressing the conus medullaris and associated with
      neurofibromatosis type 2.
AB  - STUDY DESIGN: Report of a case of subarachnoid hematoma associated with
      neurofibromatosis type 2 (NF2) in a 10-year-old girl. OBJECTIVE: To report a rare
      case of subarachnoid spontaneous hematoma associated with NF2, with no evidence
      of trauma. SETTING: Gifu, Japan. METHODS: The patient presented with severe leg
      pain. MRI revealed a subarachnoid hematoma at the level of L2 and a spinal cord
      tumor at the level of T6. The subarachnoid hematoma had low and high
      heterogeneous signal intensity on the T1-weighted image and low signal intensity
      on the T2-weighted image, indicating the presence of extracellular methemoglobin.
      The tumor and hematoma were resected. RESULTS: Pathological analysis demonstrated
      that the surgical specimen removed from the area of L2 was a hematoma and the
      specimen from T6 was a neurinoma. At follow-up 1 year after surgery, the girl
      remained neurologically asymptomatic. CONCLUSIONS: This rare case of spinal
      subarachnoid hematoma was associated with NF2. MRI was useful in establishing the
      diagnosis.

PMID- 14569269
TI  - Bruising of erect penis: a rare complication of advising young, adult, male,
      cervical spinal cord injury patient to lie prone for relief of pressure on sacral
      region.

PMID- 14569271
TI  - Nature and nurture in novelty seeking.
AB  - A sample of children (n=92), derived from a representative population sample of
      healthy young Finns (n=2149), was studied from childhood to adulthood over 14
      years to determine whether the childhood environment moderated the effect of
      dopamine receptor gene (DRD4) polymorphism on novelty seeking (NS). A significant
      interaction between the DRD4 alleles and environmental variables was observed.
      When the childhood-rearing environment was more hostile (emotionally distant, low
      tolerance of the child's normal activity, and strict discipline), the
      participants carrying any two- or five-repeat alleles of the DRD4 gene had a
      significantly greater risk of exhibiting NS scores that were above the 10th
      percentile on a population distribution of 2149 adult Finnish women and men. The
      genotype had no effects on NS when the childhood environment was more favorable.
      Although the results are preliminary, pending replication, they nevertheless
      provide important information on the long-term effects of nurture and nature on
      NS temperament.

PMID- 14569272
TI  - Expression analysis of neuregulin-1 in the dorsolateral prefrontal cortex in
      schizophrenia.
AB  - Genetic linkage and association have implicated neuregulin-1 (NRG-1) as a
      schizophrenia susceptibility gene. We measured mRNA expression levels of the
      three major isoforms of NRG-1 (ie type I, type II, and type III) in the
      postmortem dorsolateral prefrontal cortex (DLPFC) from matched patients and
      controls using real-time quantitative RT-PCR. Expression levels of three internal
      controls-GAPDH, cyclophilin, and beta-actin-were unchanged in schizophrenia, and
      there were no changes in the absolute levels of the NRG-1 isoforms. However, type
      I expression normalized by GAPDH levels was significantly increased in
      schizophrenia DLPFC (by 23%) and positively correlated with antipsychotic
      medication dosage. Type II/type I and type II/type III ratios were significantly
      decreased (18 and 23% respectively). There was no effect on the NRG-1 mRNA levels
      of genotype at two SNPs previously associated with schizophrenia, suggesting that
      these alleles are not functionally responsible for abnormal NRG-1 expression
      patterns in patients. Subtle abnormalities in the expression patterns of NRG-1
      mRNA isoforms in DLPFC may be associated with schizophrenia.

PMID- 14569273
TI  - Estrogen mediates sex differences in stress-induced prefrontal cortex
      dysfunction.
AB  - Many anxiety disorders, as well as major depressive disorder (MDD), are at least
      twice as prevalent in women as in men, but the neurobiological basis of this
      discrepancy has not been well studied. MDD is often precipitated by exposure to
      uncontrollable stress, and is frequently characterized by abnormal or disrupted
      prefrontal cortex (PFC) function. In animals, exposure to stress has been shown
      to cause PFC dysfunction, but sex differences in this effect have not been
      investigated. The present study tested male and female rats on a PFC-dependent
      working memory task after administration of FG7142, a benzodiazepine inverse
      agonist that activates stress systems in the brain. Female rats were impaired by
      lower doses than males during proestrus (high estrogen), but not during estrus
      (low estrogen). Similarly, ovariectomized females showed increased stress
      sensitivity only after estrogen replacement. These results suggest that estrogen
      amplifies the stress response in PFC, which may increase susceptibility to stress
      related disorders.

PMID- 14569274
TI  - Linkage of the dopamine receptor D1 gene to attention-deficit/hyperactivity
      disorder.
AB  - Attention-deficit/hyperactivity disorder (ADHD) has a strong genetic basis, and
      evidence from human and animal studies suggests the dopamine receptor D1 gene,
      DRD1, to be a good candidate for involvement. Here, we tested for linkage of DRD1
      to ADHD by examining the inheritance of four biallelic DRD1 polymorphisms [D1P.5
      (-1251HaeIII), D1P.6 (-800HaeIII), D1.1 (-48DdeI) and D1.7 (+1403Bsp1286I)] in a
      sample of 156 ADHD families. Owing to linkage disequilibrium between alleles at
      the four markers, only three haplotypes are common in our sample. Using the
      transmission/disequilibrium test (TDT), we observed a strong bias for
      transmission of Haplotype 3 (1.1.1.2) from heterozygous parents to their affected
      children (P=0.008). Furthermore, using quantitative trait TDT analyses, we found
      significant and positive relationships between Haplotype 3 transmission and the
      inattentive symptoms, but not the hyperactive/impulsive symptoms, of ADHD. These
      findings support the proposed involvement of DRD1 in ADHD, and implicate
      Haplotype 3, in particular, as containing a potential risk factor for the
      inattentive symptom dimension of the disorder. Since none of the four marker
      alleles comprising Haplotype 3 is predicted to alter DRD1 function, we
      hypothesize that a functional DRD1 variant, conferring susceptibility to ADHD, is
      on this haplotype. To search for such a variant we screened the DRD1 coding
      region, by sequencing, focusing on the children who showed preferential
      transmission of Haplotype 3. DNA from 41 children was analysed, and no sequence
      variations were identified, indicating that the putative DRD1 risk variant for
      ADHD resides outside of the coding region of the gene.

PMID- 14569275
TI  - The promoter -194 C polymorphism of the nicotinic alpha 7 receptor gene has a
      protective effect against the P50 sensory gating deficit.
AB  - As suggested by several studies, abnormal sensory gating measured by the P50
      paradigm could be an endophenotype predisposing to schizophrenia. In a previous
      work, we have shown a significant association between the presence of at least
      one -2 bp deletion located within exon 6 of the CHRNA7-like gene and the P50
      abnormality in the general population. A recent study involved polymorphisms
      located in the core promoter region of the CHRNA7 gene as risk factors for the
      P50 inhibitory deficit. Screening for promoter variants in a large population of
      schizophrenic patients (n=111) and control subjects (85), for whom auditory
      evoked potentials had been recorded did not allow us to replicate these results.
      By contrast, we showed a significant association between the -194 C allele and a
      T/C ratio <0.45, thus demonstrating a protective effect of this variant for the
      sensory gating deficit. Such conflicting results can be reconciled if we consider
      that the -194 C polymorphism has no causative effect, but is in linkage
      disequilibrium with other causal variations for the P50 sensory gating deficit,
      and that different alleles are in disequilibrium in different populations.

PMID- 14569276
TI  - Blunted fasting-induced decreases in plasma and CSF leptin concentrations in
      obese rats: the role of increased leptin secretion.
AB  - Fasting substantially decreases plasma leptin concentration. However, in obesity,
      the fasting-induced decrease in leptin concentration is blunted or absent. The
      objective of the current study was to determine in diet-induced obese (DIO) rats
      the contribution of altered leptin secretion and leptin expression to the blunted
      nutritional regulation of leptin concentration. Fasting-induced decreases in
      plasma leptin concentration were greater in lean (standard chow (SC)) rats
      compared to DIO (approximately 79 vs approximately 48%, P<0.05 for DIO vs SC).
      CSF leptin was significantly reduced by fasting in SC (approximately 46%) but not
      in DIO. Fasting decreased adipose tissue leptin secretion in both SC and DIO, but
      the decrease was greater in SC (average approximately 74%) compared to DIO
      (average approximately 44%, P<0.05, DIO vs SC). Additionally, leptin secretion in
      fasted DIO was substantially greater (average approximately 175%) than in fasted
      SC (P<0.05). Adipose tissue leptin protein content was increased by approximately
      80% in DIO compared to SC (P<0.05). We conclude that a probable cause of blunted
      fasting-induced decreases in leptin concentration in obesity is elevated leptin
      secretion, which possibly results from increased leptin gene expression.

PMID- 14569277
TI  - Vigorous exercise and the population distribution of body weight.
AB  - BACKGROUND: While the benefits of vigorous exercise on body weight and regional
      adiposity are well established, whether these benefits affect equally the highest
      and lowest portions of the weight distribution have not been previously reported.
      The impact of exercise on the more extreme body weights and body circumferences
      is clinically important because these values represent individuals at greatest
      health risk. METHOD: Self-reported weights and body circumferences from a cross
      sectional sample of 7288 male and 2326 female runners were divided into five
      strata, according to the distances run per week and within each stratum the 5th,
      10th, 25th, 50th, 75th, 90th and 95th percentiles were determined. Least-squares
      regression was then employed at each percentile to determine the dose-response
      relationship between running distance and adiposity as determined by body mass
      index (BMI) and self-reported circumferences of the waist, hip and chest.
      RESULTS: Per kilometer run per week, the associated decline for BMI was three
      fold greater at the 95th than at the 5th percentile in men, and six-fold greater
      at the 95th than the 5th percentile in women (all P<0.001). Reported waist
      circumference also declined more sharply at the 95th percentile than at the 5th
      percentile in men (-0.13 +/- 0.02 vs -0.06 +/- 0.01 cm per km/week) and women (
      0.18 +/- 0.04 vs -0.05 +/- 0.01 cm per km/week). In women, both hip and chest
      circumferences declined more sharply per kilometer run at the 95th percentile
      than at the 5th percentile. CONCLUSIONS: These results are consistent with the
      hypothesis that running promotes the greatest weight loss specifically in those
      individuals who have the most to gain from losing weight. Comparisons based on
      average BMI or average body circumferences are likely to underestimate the health
      benefits of running because of the J-shaped relationship between adiposity and
      mortality. Whether the observed cross-sectional associations are primarily due to
      exercise-induced weight loss or self-selection remains to be determined.

PMID- 14569278
TI  - Effects of manipulated palatability on appetite depend on restraint and
      disinhibition scores from the Three-Factor Eating Questionnaire.
AB  - OBJECTIVES: The present study evaluated the effects of dietary restraint on short
      term appetite in response to manipulated palatability. DESIGN: The effects of
      palatability on appetite during a lunchtime meal were assessed by contrasting
      intake of a bland and palatable version of a simple food (within subject). To
      test how responses to palatability varied with restraint, these meals consumed by
      women were classified according to restraint (R) and disinhibition (D) scores
      from the Three-Factor Eating Questionnaire (TFEQ) as high R/high D (HR-HD), high
      R/low D (HR-LD), low R/high D (LR-HD) and low R/low D (LR-LD). SUBJECTS: A total
      of 40 normal-weight women subdivided into four groups based on TFEQ scores.
      MEASUREMENTS: The overall intake, appetite and hedonic ratings before, during and
      after the meal. RESULTS: All groups ate similar amounts of the bland food, but
      the LR-HD group ate significantly more of the palatable version than the other
      groups, whereas HR-LD did not increase intake in response to palatability. Hunger
      increased on tasting the palatable food in all but the HR-LD group, and this
      group ended both meals more hungry/less full than the others. CONCLUSION: Women
      classified as HR-LD were unresponsive to manipulated palatability, whereas those
      classified as LR-HD were over-responsive. These findings imply that some
      individuals are prone to over-respond to palatability and so are at greater risk
      of developing obesity, whereas others are able to resist the effects of
      palatability and so successfully self-restrict their food intake. Implications
      for obesity are discussed.

PMID- 14569279
TI  - Controlled outcome evaluation of the First Step Program: a daily physical
      activity intervention for individuals with type II diabetes.
AB  - OBJECTIVE: To conduct a randomised trial of a physical activity (PA)
      intervention, The First Step Program (FSP) for adults with type II diabetes.
      DESIGN: A 16-week intervention study and 24-week follow-up assessment.
      PARTICIPANTS: A total of 47 overweight/obese, sedentary individuals (age=52.7 +/-
      5.2 y; BMI=33.3 +/- 5.6 kg/m2) recruited through a diabetes education centre.
      MEASUREMENTS:  PRIMARY OUTCOME: daily PA assessed by pedometer (steps/day).
      SECONDARY OUTCOMES: anthropometric measures (weight, BMI, waist girth, hip
      girth); indicators of cardiovascular health (resting heart rate and blood
      pressure); glycemic control (fasting glucose, insulin, HbA1c, glucose
      concentration 120 min postglucose load); plasma lipid status (total cholesterol,
      HDL cholesterol, LDL cholesterol, and triglycerides). RESULTS: Relative to the
      CONTROL group, FSP participants increased their PA >3000 steps/day (approximately
      30 min/day) during the intervention (P<0.0001). Waist and hip girth decreased
      (approximately 2-3 cm), but did not differ significantly between groups.
      Significant changes did not emerge for any of the other variables. CONCLUSIONS:
      The FSP is a practical intervention that elicits an immediate and profound change
      in walking behaviour. Such change is an important 'first step' towards increasing
      the volume and/or intensity of PA necessary to improve long-term health outcomes
      in this largely sedentary and overweight or obese population. Relapse by 24 weeks
      indicates that other strategies such as booster sessions are needed to maintain
      lifestyle change. Further research must determine realistic and responsive health
      outcomes for this population that are achievable through practical, real-world
      programming.

PMID- 14569280
TI  - Multiple linked mouse chromosome 7 loci influence body fat mass.
AB  - BACKGROUND: Congenic mouse strains contain donor mouse strain DNA in genomes
      otherwise identical to a background strain. They can be used to identify defined
      chromosomal regions containing obesity genes with small effects. OBJECTIVE: : The
      objective of this study was to discover congenic strains containing genes that
      influence body fat in mice and to examine interactions between these genes.
      DESIGN: A survey of congenic strains showed that the B6.C-Tyr(c) H1(b) Hbb(d)/By
      (B6.C-H1) congenic strain, with a 24 centiMorgan (cM) donor region from strain
      BALB/cBy on chromosome 7, had 50% less fat than background C57BL/6By (B6By) mice.
      The congenic donor region was then divided into 11 smaller overlapping
      subcongenic regions. Genotype effects on obesity traits in the subcongenics were
      determined by breeding heterozygotes for each line and comparing phenotypes of
      littermates with different donor genotypes. RESULTS: At least three subcongenic
      strains, two with overlapping donor regions and one with a nonoverlapping donor
      strain region, were found to exhibit significant influences of donor region
      genotype on obesity. A cross of the two overlapping subcongenics demonstrated
      that a single gene in the overlap region could not account for the observed
      obesity effects. We also observed significant obesity differences between
      genetically identical progeny that were contingent on the genotype of their
      subcongenic mothers. CONCLUSIONS: These results demonstrate the existence of at
      least three genes influencing obesity in three subcongenic strains with donor
      strain chromosomal regions whose size ranges from 0.5 to 5 cM. A maternal effect
      gene influencing obesity may be present in some subcongenic strains.

PMID- 14569281
TI  - Incorporation of epitope-tagged viral sigma3 proteins to reovirus virions.
AB  - Tagging of viral capsid proteins is a powerful tool to study viral assembly; it
      also raises the possibility of using viral particles to present exogenous
      epitopes in vaccination or gene therapy strategies. The ability of reoviruses to
      induce strong mucosal immune response and their large host range and low
      pathogenicity in humans are some of the advantages of using reoviruses in such
      applications. In the present study, the feasibility of introducing foreign
      epitopes, "tags", to the sigma3 protein, a major component of the reovirus outer
      capsid, was investigated. Among eight different positions, the amino-terminal end
      of the protein appeared as the best location to insert exogenous sequences.
      Additional amino acids at this position do not preclude interaction with the
      micro1 protein, the other major constituent of the viral outer capsid, but
      strongly interfere with micro1 to micro1C cleavage. Nevertheless, the tagged
      sigma3 protein was still incorporated to virions upon recoating of infectious
      subviral particles to which authentic sigma3 protein was removed by proteolysis,
      indicating that micro1 cleavage is not a prerequisite for outer capsid assembly.
      The recently published structure of the sigma3- micro1 complex suggests that the
      amino-terminally inserted epitope could be exposed at the outer surface of viral
      particles.

PMID- 14569283
TI  - Shifts in community composition provide a mechanism for maintenance of activity
      of soil yeasts in the presence of elevated copper levels.
AB  - Soil dilution plates were prepared from different soil samples using a solid
      synthetic selective medium containing (i). glucose as carbon source, (ii).
      thymine as nitrogen source, (iii). vitamins, (iv). minerals, and (v).
      chloramphenicol as antibacterial agent. Using the Diazonium Blue B colour
      reaction, it was found that both ascomycetous and basidiomycetous yeasts were
      able to grow on this medium. Subsequently, the medium was used to enumerate
      yeasts in soil microcosms prepared from four different soil samples, which were
      experimentally treated with the fungicide copper oxychloride, resulting in copper
      (Cu) concentrations of up to 1000 ppm. The selective medium supplemented with 32
      ppm of Cu was used to enumerate Cu-resistant yeasts in the microcosms. The
      results showed that the addition of Cu at concentrations >or=approximately 1000
      ppm did not have a significant effect on total number of yeasts in the soil.
      Furthermore, it was found that Cu-resistant yeasts were present in all the soil
      samples, regardless of the amount of Cu that the soil was challenged with. At the
      end of the incubation period, yeasts in the microcosms with zero and
      approximately 1000 ppm of additional Cu were enumerated, isolated, and identified
      with sequence analyses of the D1/D2 600-650 bp region of the large subunit of
      ribosomal DNA. Hymenomycetous species dominated in the control soil, while higher
      numbers of the urediniomycetous species were found in the soil that received Cu.
      These observations suggest that urediniomycetous yeasts may play an important
      role in re-establishing overall microbial activity in soils, following
      perturbations, such as the addition of Cu-based fungicides.

PMID- 14569282
TI  - Mechanisms of cadmium resistance in anaerobic bacterial enrichments degrading
      pentachlorophenol.
AB  - The mechanisms of heavy-metal resistance used by adapted sulfidogenic and
      methanogenic enrichments degrading pentachlorophenol in the presence of cadmium
      (Cd) were studied. The enrichment cultures adapted to and readily tolerated
      bioavailable Cd concentrations up to 50 ppm while degrading an equal
      concentration of pentachlorophenol. Both cultures removed >95% of the Cd from
      solution. Transmission electron micrographs revealed (i). the presence of
      electron-dense particles surrounding the cells in the sulfidogenic enrichments
      and (ii). the unusual clumping of cells and the presence of an exopolymer in the
      methanogenic enrichments. Energy dispersive X-ray analysis showed that the
      sulfidogenic enrichments removed Cd by extracellular precipitation of cadmium
      sulfide, while the methanogenic enrichment culture removed Cd by extracellular
      sequestration of Cd into the exopolymer.

PMID- 14569284
TI  - The infection process of Colletotrichum graminicola and relative aggressiveness
      on four turfgrass species.
AB  - Detached 3-week-old leaves of Agrostis palustris, Lolium perenne, Poa annua, and
      Poa pratensis were inoculated with conidial suspensions of two isolates of
      Colletotrichum graminicola obtained from A. palustris. Inoculated leaves were
      incubated at 23 degrees C under high relative humidity (>95%). The infection
      process was investigated by light microscopy from 2 to 168 h after inoculation
      (AI). Spore germination was observed within 2 h AI, appressoria within 6 h AI,
      and penetration pores within 8 h AI on all four hosts. Infection hyphae were
      observed inside epidermal cells within 24 h AI on all four hosts, but
      significantly greater infection was observed in A. palustris and P. annua than in
      L. perenne or P. pratensis at both 96 and 120 h AI. Acervuli appeared on leaves
      of A. palustris at 72 h AI and on L. perenne at 96 h AI but were not found on
      either P. annua or P. pratensis during the first 168 h AI. The infection process
      was similar to that reported for C. graminicola from other hosts; however,
      disease development of the two isolates of C. graminicola from A. palustris was
      faster or fungal growth more extensive on detached leaf tissue of A. palustris
      than on other turfgrass species tested.

PMID- 14569285
TI  - Indole can act as an extracellular signal to regulate biofilm formation of
      Escherichia coli and other indole-producing bacteria.
AB  - We demonstrated previously that genetic inactivation of tryptophanase is
      responsible for a dramatic decrease in biofilm formation in the laboratory strain
      Escherichia coli S17-1. In the present study, we tested whether the biochemical
      inhibition of tryptophanase, with the competitive inhibitor oxindolyl-L-alanine,
      could affect polystyrene colonization by E. coli and other indole-producing
      bacteria. Oxindolyl-L-alanine inhibits, in a dose-dependent manner, indole
      production and biofilm formation by strain S17-1 grown in Luria-Bertani (LB)
      medium. Supplementation with indole at physiologically relevant concentrations
      restores biofilm formation by strain S17-1 in the presence of oxindolyl-L-alanine
      and by mutant strain E. coli 3714 (S17-1 tnaA::Tn5) in LB medium. Oxindolyl-L
      alanine also inhibits the adherence of S17-1 cells to polystyrene for a 3-h
      incubation time, but mutant strain 3714 cells are unaffected. At 0.5 mg/mL,
      oxindolyl-L-alanine exhibits inhibitory activity against biofilm formation in LB
      medium and in synthetic urine for several clinical isolates of E. coli,
      Klebsiella oxytoca, Citrobacter koseri, Providencia stuartii, and Morganella
      morganii but has no affect on indole-negative Klebsiella pneumoniae strains. In
      conclusion, these data suggest that indole, produced by the action of
      tryptophanase, is involved in polystyrene colonization by several indole
      producing bacterial species. Indole may act as a signalling molecule to regulate
      the expression of adhesion and biofilm-promoting factors.

PMID- 14569286
TI  - Regulation of toxA by PtxR in Pseudomonas aeruginosa PA103.
AB  - Exotoxin A (ETA) production in Pseudomonas aeruginosa requires the regulatory
      locus regAB. Pseudomonas aeruginosa PA103 produces significantly higher levels of
      ETA than the prototypic strain PAO1 does, partly because of differences in the
      regAB locus. Other factors that contribute to this variation are not known. We
      previously described the P. aeruginosa gene ptxR that positively regulates
      production of ETA through regAB. ETA production was enhanced but still iron
      regulated in the PAO1 strain PAO1-XR that carries two copies of ptxR on its
      chromosome. Here we determine whether ptxR regulation of ETA is different in
      PA103. In contrast to PAO1-XR, ETA activity produced by PA103-2R, a PA103 strain
      carrying two copies of ptxR, is enhanced tenfold and partially deregulated in the
      presence of iron. Real-time PCR transcriptional analysis showed that the copy
      number of toxA mRNA in PA103-2R is significantly higher than in PA103 in both the
      presence and absence of iron, yet no similar increase in either regAB or ptxR
      mRNA copy number was detected. The integrated plasmid together with adjoining DNA
      was retrieved from the PA103-2R chromosome to determine whether integration
      induced DNA changes played a role in this phenotype. Introduction of the
      retrieved plasmid in PA103 produced a phenotype similar to that of PA103-2R.
      Sequence analysis of the plasmid revealed the loss of 322 bp within the region 3'
      of ptxR. A plasmid construct carrying a 4-bp insertion in this same region
      produced in PA103 a phenotype similar to that of PA103-2R. Our results suggest
      that the effect of ptxR on toxA expression is different in PA103 than in PAO1 and
      that this variation in PA103-2R does not occur solely through regAB. Changes
      within the region 3' of ptxR are critical for the production of the unique PA103
      2R phenotype, which occurs in trans and requires intact ptxR, but is not caused
      by ptxR overexpression.

PMID- 14569287
TI  - Microbial ecology of Bacillus thuringiensis: fecal populations recovered from
      wildlife in Korea.
AB  - A total of 34 fecal samples, collected from 14 species of wild mammals in Korea,
      were examined for the occurrence of Bacillus thuringiensis. The organism was
      detected in 18 (53%) samples. Among the three food-habit groups, herbivorous
      animals yielded the highest frequency (69%) of samples positive for B.
      thuringiensis, followed by omnivorous animals (50%). Of the six fecal samples
      from carnivorous animals, only one sample contained B. thurin giensis. Among 527
      isolates belonging to the Bacillus cereus - B. thuringiensis group, 43 (8%) were
      assigned to B. thurin giensis on the basis of the formation of parasporal
      inclusions. Of the 43 isolates, 13 were serologically allocated to the nine H
      antigenic serotypes: H3ad (serovar sumiyoshiensis), H15 (dakota), H17/27
      (tohokuensis/ mexicanensis), H19 (tochigiensis), H21 (colmeri), H29 (amagiensis),
      H31/49 (toguchini/muju), H42 (jinghongiensis), and H44 (higo). Other isolates
      were untestable or untypable by the 55 reference H antisera available.
      Insecticidal activity was associated with 23% of the fecal populations: three
      isolates killed larvae of the silkworm, Bombyx mori (Lepidoptera), and seven
      exhibited larvicidal activity against the mosquito, Aedes aegypti (Diptera).
      There was no larvicidal activity against the three lepidopterous insects:
      Plutella xylostella, Spodoptera exigua, and Spodoptera litura. The overall
      results suggest that wild animals in Korea are in contact with naturally
      occurring B. thuringiensis at high frequencies through the daily food intake of
      plants.

PMID- 14569288
TI  - Adhesion of probiotic lactobacilli to chick intestinal mucus.
AB  - In the present work, interactions between three Lactobacillus strains
      (Lactobacillus fermentum CRL1015, Lactobacillus animalis CRL1014, and
      Lactobacillus fermentum CRL1016) and chicken small intestinal mucus were
      determined. Three lactobacilli isolated from chicken and selected by their
      potentially probiotic properties were able to grow in mucus preparations. Three
      peaks from gel filtration chromatography of intestinal mucus were obtained. The
      adhesion to three mucus fractions (I, II, and III), especially fraction III, was
      higher (P < 0.01) in L. fermentum CRL1015 than L. animalis CRL1014. Pretreatment
      of this fraction with proteases and metaperiodate showed lower (P < 0.01)
      adhesion values than that of the control, suggesting that a glycoprotein from the
      mucus acts as a receptor for L. fermentum CRL1015. Highest adhesion values were
      obtained at pH 7 and 42 degrees C, and neither the removal of divalent cations
      with ethylenediaminetetraacetic acid (EDTA) nor the addition of calcium produced
      significant variation from the adhesion values of the control (P > 0.01). This
      adhesion was only inhibited by N-acetyl-glucosamine. Salmonella pullorum and
      Salmonella gallinarum showed high (P < 0.01) values of adhesion to chick
      intestinal mucus. The results obtained from assays of the inhibition of adherence
      of Salmonella spp. to mucus, immobilized in polystyrene tissue culture wells,
      indicated that the pathogen adhesion was not reduced by lactobacilli (P > 0.05)
      or their spent culture supernatants (P > 0.05), suggesting that these strains did
      not interfere with the binding sites for Salmonella spp. adhesion to the small
      intestinal mucus.

PMID- 14569289
TI  - A low molecular weight enterotoxic hemolysin from clinical Enterobacter cloacae.
AB  - Seven of 50 Enterobacter cloacae strains from clinical isolates produced small
      turbid zones of hemolysis in horse and sheep blood agar plates, and the culture
      supernatants were also positive for hemolytic activity. The hemolysin was
      partially purified from the culture supernatant of E. cloacae by ultrafiltration
      (PM-10 membrane) and extraction with acetone. Semipurified hemolysin was stable
      to heating (100 degrees C, 30 min) and was soluble in organic solvents (acetone,
      ethanol, and methanol). The toxin showed no loss of biological activity after
      treatment with trypsin and was stable to acid treatment at pH 2.0 but not at a pH
      greater than 7.0. In the rat intestinal loop assay, the hemolysin caused
      hemorrhagic fluid accumulation and severe histological alterations. These
      findings indicate that this hemolysin may be a putative virulence factor in E.
      cloacae infections.

PMID- 14569290
TI  - Effects of Gypsophila saponins on bacterial growth kinetics and on selection of
      subterranean clover rhizosphere bacteria.
AB  - Plant secondary metabolites, such as saponins, have a considerable impact in
      agriculture because of their allelopathic effects. They also affect the growth of
      soil microorganisms, especially fungi. We investigated the influence of saponins
      on rhizosphere bacteria in vitro and in soil conditions. The effects of
      gypsophila saponins on the growth kinetics of rhizosphere bacteria were studied
      by monitoring the absorbance of the cultures in microtiter plates. Gypsophila
      saponins (1%) increased the lag phase of bacterial growth. The impact of
      gypsophila saponins on subterranean clover rhizosphere was also investigated in a
      pot experiment. The addition of gypsophila saponins did not modify clover biomass
      but significantly increased (twofold with 1% saponins) the weight of adhering
      soil. The number of culturable heterotrophic bacteria of the clover rhizosphere
      was not affected by the addition of gypsophila saponins. Nevertheless, the
      phenotypical characterization of the dominant Gram-negative strains of the clover
      rhizosphere, using the Biolog system, showed qualitative and quantitative
      differences induced by 1% saponins. With the addition of saponins, the
      populations of Chryseomonas spp. and Acinetobacter spp., the two dominant
      culturable genera of control clover, were no longer detectable or were
      significantly decreased, while that of Aquaspirillum dispar increased and
      Aquaspirillum spp. became the major genus. Aquaspirillum dispar and Aquaspirillum
      spp. were also the dominant rhizosphere bacteria of Gypsophila paniculata, which
      greatly accumulates these saponins in its roots. These results suggest that
      saponins may control rhizosphere bacteria in soil through rhizodeposition
      mechanisms.

PMID- 14569291
TI  - Expression and export of a Ruminococcus albus cellulase in Butyrivibrio
      fibrisolvens through the use of an alternative gene promoter and signal sequence.
AB  - Ruminococcal cellulase (Ruminococcus albus F-40 endoglucanase EgI) was
      successfully expressed in Butyrivibrio fibrisolvens OB156C, using the erm
      promoter from pAMbeta1. A newly identified signal peptide coding region of xynA
      from B. fibrisolvens 49 allowed efficient translocation of the foreign EgI into
      the extracellular fraction. First, B. fibrisolvens xynA with or without its own
      putative signal peptide (XynA SP) coding region was cloned into a shuttle vector
      to transform B. fibrisolvens OB156C. Both plasmids caused a 2- to 2.4-fold
      increase in xylanase activity. The transformant expressing XynA with the signal
      peptide showed a significantly higher proportion of activity in the extracellular
      fraction than the transformant with XynA lacking the signal peptide (75% vs.
      19%), demonstrating the significance of XynA SP in the translocation of the
      expressed enzyme. Second, using the XynA SP coding region, secretion of EgI was
      attempted in B. fibrisolvens. Since the signal peptide of R. albus EgI did not
      function in B. fibrisolvens, it was replaced with the XynA SP. A high activity
      variant of EgI containing the XynA SP was transcribed using the erm promoter,
      resulting in a 27-fold increase in endoglucanase activity, most of which (>93%)
      was in the extracellular fraction of the B. fibrisolvens transformant. EgI
      without the XynA SP was scarcely detected in the extracellular fraction (<10%).

PMID- 14569292
TI  - Survival and colonization of rhizobacteria in a tomato transplant system.
AB  - Plant-growth-promoting rhizobacteria (PGPR) are used on crops most often as seed
      treatments; however, an alternative application method for transplanted
      vegetables is mixing PGPR into the soilless medium in which the transplants are
      grown. Studies were undertaken to compare root colonization and persistence of
      rifampicin-resistant mutants of PGPR strains Bacillus pumilus SE34 and
      Pseudomonas fluorescens 89B61, SE34r and 89B61r, on tomato as a function of
      application method. When the bacteria were incorporated into Promix soilless
      medium at log 6, 7, and 8 colony- forming units/g, populations of strain SE34r
      per gram of medium maintained the initial inoculum densities, while populations
      of 89B61r decreased approximately one to two orders of magnitude by 4 weeks after
      planting. The populations of each PGPR strain colonizing roots after application
      into the soilless medium showed a similar pattern at 6 weeks as that at 4 weeks
      after planting, with higher populations on the whole roots and lateral roots than
      on the taproots. Strain SE34r but not 89B61r moved upwards and colonized the
      phyllosphere when incorporated into the soilless medium. Following application as
      seed treatment, populations of SE34r were significantly higher on upper roots and
      on the taproot than were populations following application through the soilless
      medium. Conversely, populations were higher on lower roots and lateral roots
      following application through the soilless medium than were populations following
      application as seed treatment. While strain SE34 enhanced plant growth with
      application both to the medium and as seed treatment, the level of growth
      promotion was significantly greater with application in the soilless medium. The
      results indicate that PGPR can be successfully incorporated into soilless media
      in vegetable transplant production systems.

PMID- 14569293
TI  - Magnetic bead hybridization to detect enterotoxigenic Escherichia coli strains
      associated with cattle in environmental water sources.
AB  - A magnetic capture hybridization - polymerase chain reaction (MCH-PCR) method was
      used to increase the detection sensitivity of the enterotoxin gene LTIIa, used as
      a biomarker for waste in environmental samples. The samples were collected from
      cow lagoons of different farms and from environmental waters. Total DNA was
      extracted from colonies grown on mTEC medium or directly from environmental
      samples. The cow-specific Escherichia coli LTIIa gene was used as a DNA marker. A
      LTIIa-specific oligonucleotide probe was designed to capture the LTIIa marker
      during the MCH, followed by PCR. Varying levels of humic acid were added to the
      DNA extracts to evaluate the sensitivity and effectiveness of MCH-PCR. The
      minimal detection limit of MCH-PCR for the LTIIa gene was 2.5 ag/muL DNA. In the
      presence of humic acid, MCH-PCR was able to increase the detection sensitivity 10
      000-fold over that of conventional PCR. The MCH-PCR could also detect one cell
      with the LTIIa DNA marker in a 1-L seeded environmental water sample. Results in
      this study indicate that MCH-PCR is more sensitive than nested PCR in testing
      environmental samples.

PMID- 14569294
TI  - A calcium-dependent bacterial surface protein is involved in the attachment of
      rhizobia to peanut roots.
AB  - As part of a project to characterize molecules involved in the crack-entry
      infection process leading to nodule development, a microscopic assay was used to
      visualize the attachment of cells of Bradyrhizobium sp. strains SEMIA 6144 and
      TAL 1000 (labelled by introducing a plasmid expressing constitutively the green
      fluorescent protein GFP-S65T) to Arachis hypogaea L. (peanut). Qualitative and
      quantitative results revealed that attachment was strongly dependent on the
      growth phase of the bacteria. Optimal attachment occurred when bacteria were at
      the late log or early stationary phase. Cell surface proteins from the
      Bradyrhizobium sp. strains inhibited the attachment when supplied prior to the
      attachment assay. Root incubation with a 14-kDa protein (eluted from sodium
      dodecyl sulphate - gel electrophoresis of the cell surface fraction) prior to the
      attachment assay resulted in a strong decrease of attachment. The adhesin
      appeared to be a calcium-binding protein, since cells treated with EDTA were
      found to be able to bind to adhesin-treated peanut roots. Since this protein has
      properties identical to those reported for rhicadhesin, we propose that this
      adhesin is also involved in the attachment process of rhizobia to root legumes
      that are infected by the crack-entry process.

PMID- 14569296
TI  - Inactivation and conformational changes of creatine kinase at low concentrations
      of hexafluoroisopropanol solutions.
AB  - Using the methods of far-ultraviolet circular dichroism (CD) spectra,
      fluorescence spectra, and enzyme activity assays, the inactivation and
      conformational changes of creatine kinase (CK) induced by 1,1,1,3,3,3-hexafluoro
      2-propanol (hexafluoroisopropanol (HFIP)) of different concentrations were
      investigated. To avoid the aggregation of CK that occurs with high HFIP,
      concentrations of 0%-5% HFIP were used in this study. The CD spectra showed that
      HFIP concentrations above 2.5% strongly induced the formation of secondary
      structures of CK. No marked conformational changes were observed at low
      concentrations of HFIP (0%-2.5%). After incubation with 0.2% HFIP for 10 min, CK
      lost most of its activity. The kinetic theory of the substrate reaction during
      irreversible inhibition of enzyme activity described previously by Tsou was
      applied to study the kinetics of CK inactivation during denaturation by HFIP. The
      inactivation rate constants for the free enzyme and the substrate-enzyme complex
      were determined by Tsou's method. The results suggested that low concentrations
      of HFIP had a high potential to induce helices of protein and that the active
      site of the enzyme was situated in a limited and flexible region of the enzyme
      molecule that was more susceptible to the denaturant than was the protein as a
      whole.

PMID- 14569297
TI  - Beta1 integrins are distributed in adhesion structures with fibronectin and
      caveolin and in coated pits.
AB  - Integrins are found in adhesion structures, which link the extracellular matrix
      to cytoskeletal proteins. Here, we attempt to further define the distribution of
      beta1 integrins in the context of their association with matrix proteins and
      other cell surface molecules relevant to the endocytic process. We find that
      beta1 integrins colocalize with fibronectin in fibrillar adhesion structures. A
      fraction of caveolin is also organized along these adhesion structures. The
      extracellular matrix protein laminin is not concentrated in these structures. The
      alpha4beta1 integrin exhibits a distinct distribution from other beta1 integrins
      after cells have adhered for 1 h to extracellular matrix proteins but is
      localized in adhesion structures after 24 h of adhesion. There are differences
      between the fibronectin receptors: alpha5beta1 integrins colocalize with adaptor
      protein-2 in coated pits, while alpha4beta1 integrins do not. This parallels our
      earlier observation that of the two laminin receptors, alpha1beta1 and
      alpha6beta1, only alpha1beta1 integrins colocalize with adaptor protein-2 in
      coated pits. Calcium chelation or inhibition of mitogen-activated protein kinase
      kinase, protein kinase C, or src did not affect localization of alpha1beta1 and
      alpha5beta1 integrins in coated pits. Likewise, the integrity of coated-pit
      structures or adhesion structures is not required for integrin and adaptor
      protein-2 colocalization. This suggests a robust and possibly constitutive
      interaction between these integrins and coated pits.

PMID- 14569299
TI  - Differential expression of Akt, PPARgamma, and PGC-1 during hibernation in bats.
AB  - The effects of hibernation on the expression of Akt (protein kinase B), the
      peroxisome proliferator-activated receptor gamma isoform (PPARgamma), and the
      PPARgamma coactivator PGC-1 were assessed in seven tissues of the little brown
      bat, Myotis lucifugus. Western blotting revealed that the levels of active
      phosphorylated Akt were strongly reduced in brain, kidney, liver, and white
      adipose during torpor as compared with aroused animals and that total Akt protein
      was also reduced in white adipose during torpor. By contrast, both total and
      phospho-Akt were elevated in brown adipose tissue, the thermogenic organ.
      PPARgamma and PGC-1 levels showed parallel changes in all organs. Both were
      strongly suppressed in brain, but levels increased significantly in all other
      organs during hibernation (except for PGC-1 in heart). Reduced Akt activity is
      consistent with a probable reduced insulin response during torpor that
      facilitates the mobilization of lipid reserves for fuel supply and is further
      supported by increased gene expression of enzymes and proteins involved in lipid
      catabolism under the stimulation of enhanced PPARgamma and PGC-1 levels.

PMID- 14569298
TI  - Expression of bovine lactoferrin and lactoferrin N-lobe by recombinant
      baculovirus and its antimicrobial activity against Prototheca zopfii.
AB  - Lactoferrin (LF) is a multifunctional, iron-binding glycoprotein found in
      secretory fluids of mammals. In this study, DNA encoding bovine lactoferrin (bLF)
      or the N-terminal half of bLF (bLF N-lobe) was inserted into a baculovirus
      transfer vector, and a recombinant virus expressing bLF or bLF N-lobe was
      isolated. An 80-kDa bLF-related protein expressed by the recombinant baculovirus
      was detected by monoclonal antibodies against bLF N-lobe and the C-terminal half
      of bLF (bLF C-lobe). A 43-kDa bLF N-lobe-related protein expressed by the
      recombinant baculovirus was detected by anti-bLF N-lobe monoclonal antibody, but
      not by anti-bLF C-lobe monoclonal antibody. These proteins were also secreted
      into the supernatant of insect cell cultures. Recombinant bLF (rbLF) and bLF N
      lobe (rbLF N-lobe) were affected by tunicamycin treatment, indicating that rbLF
      and rbLF N-lobe contain an N-linked glycosylation site. Antimicrobial activity of
      these recombinant proteins against Prototheca zopfii (a yeast-like fungus that
      causes bovine mastitis) was evaluated by measuring the optical density of the
      culture microplate. Prototheca zopfii was sensitive to rbLF and rbLF N-lobe, as
      well as native bLF. There was no difference in antimicrobial activity between
      rbLF N-lobe and bLF C-lobe.

PMID- 14569301
TI  - Translocation of transcription regulators into the nucleus during granulocyte
      commitment of HL-60 cells.
AB  - Expression of transcription factors required for lineage commitment of
      differentiating cells (C/EBPbeta and c-Myb) and for survival of differentiated
      cells (STATs and NFkappaB) was examined in the HL-60 cell line. Differentiation
      was induced by treating the cells with retinoic acid. c-Myb expression in the
      nucleus restored at the precommitment stage (18 h) what concurred with the
      highest nuclear level of C/EBPbeta, which suggests a combinatorial interaction of
      these transcription factors in the granulocytic signalling pathway. Expression of
      STAT5a and STAT5b varied during differentiation, whereas no significant changes
      were seen in STAT3 levels. Increased cytosolic level of NFkappaB p65 during
      precommitment and commitment stages of granulocytic differentiation coincided
      with augmentation of the STAT5a protein level, which could be evidence of their
      possible cooperation during granulocytic-lineage commitment of HL-60 cells. Our
      results suggest that the studied transcription factors cooperatively promote
      signalling in the differentiating promyelocytic HL-60 cell line in response to
      retinoic acid.

PMID- 14569300
TI  - The bacterial receptor protein, transferrin-binding protein B, does not
      independently facilitate the release of metal ion from human transferrin.
AB  - Pathogenic Gram-negative bacteria of the Pasteurellaceae and Neisseriaceae
      acquire iron for growth from host transferrin through the action of specific
      surface receptors. Iron is removed from transferrin by the receptor at the cell
      surface and is transported across the outer membrane to the periplasm. A
      periplasmic binding protein-dependent pathway subsequently transports iron into
      the cell. The transferrin receptor is composed of a largely surface-exposed
      lipoprotein, transferrin binding protein B, and a TonB-dependent integral outer
      membrane protein, transferrin binding protein A. To examine the role of
      transferrin binding protein B in the iron removal process, complexes of
      recombinant transferrin binding protein B and transferrin were prepared and
      compared with transferrin in metal-binding and -removal experiments. A
      polyhistidine-tagged form of recombinant transferrin binding protein B was able
      to purify a complex with transferrin that was largely monodisperse by dynamic
      light scattering analysis. Gallium was used instead of iron in the metal-binding
      studies, since it resulted in increased stability of recombinant transferrin
      binding protein B in the complex. Difference absorption spectra were used to
      monitor removal of gallium by nitrilotriacetic acid. Kinetic and equilibrium
      binding studies indicated that transferrin binds gallium more tightly in the
      presence of transferrin binding protein B. Thus, transferrin binding protein B
      does not facilitate metal ion removal and additional components are required for
      this process.

PMID- 14569302
TI  - Effect of fetal hemoglobin-stimulating medicines on the interaction of DNA and
      protein of important erythroid regulatory elements.
AB  - Beta-Thalassemia is the most common single gene disorder in the world, which is
      caused by the imbalance between alpha-globin chain and beta-globin chain
      synthesis. Several medicines, such as 5-azacytidine, hydroxyurea, cytarabine,
      vinblatine, butyrate, and myleran, have been shown to be able to reactivate gamma
      globin chain synthesis during the adult stage, and some of them (5-azacytidine,
      hydroxyurea, myleran, and butyrate) have been used clinically to treat
      thalassemia and sickle cell disease. Much research efforts are focusing on the
      determination of the underlying mechanisms of medicine action. In this
      experiment, as an effort to probe the underlying mechanism of medicine action, we
      used ligation-mediated polymerase chain reaction and in vivo footprinting methods
      to study the DNA-protein interaction at critical erythroid regulatory elements
      after hydroxyurea or myleran administration to mice. Our results showed that the
      patterns of in vivo footprints at both the hypersensitive site 2 of the locus
      control region and the beta-globin gene promoter were changed after medicine
      treatment. We proposed based on these results that the medicines' administration
      might result in a change in the interaction between trans-acting factors and cis
      acting elements at these regions. These changes might influence the assembly of
      the transcription complex and, lastly, influence the expression of the beta
      globin gene.

PMID- 14569303
TI  - The product of the bacteriophage lambda W gene: purification and properties.
AB  - Gene W is one of the 10 genes that control the morphogenesis of the bacteriophage
      lambda head. The morpho genesis of the phage lambda head proceeds through the
      synthesis of an intermediate assembly called the prohead. This is an empty shell
      into which the bacteriophage DNA is introduced--packaged--by the phage enzyme DNA
      terminase. The product of W (gpW) acts after DNA packaging, but before the
      addition of another phage product, gene product FII, and before the addition of
      tails. The role of gpW is unknown. The structure of N- and C-tagged gpW has been
      previously determined by nuclear magnetic resonance (NMR) spectroscopy. Here we
      report some of the properties of the native protein. The purification of gpW to
      homogeneity, overproduced by a plasmid derivative, is described. To obtain large
      amounts of the protein, the ribosome-binding site had to be modified, showing
      that inefficient translation of the message is the main mechanism limiting W gene
      expression. The molecular weight of the protein is in close agreement to the
      value predicted from the DNA sequence of the gene, which suggests that it is not
      post-transcriptionally modified. It behaves as a monomer in solution.
      Radioactively labeled gpW is incorporated into phage particles in in vitro
      complementation, showing that gpW is a structural protein. The stage at which gpW
      functions and other circumstantial evidence support the idea that six molecules
      of gpW polymerize on the connector before the incorporation of six molecules of
      gpFII and before the tail attaches.

PMID- 14569304
TI  - Purification of bovine cathepsin B: proteomic characterization of the different
      forms and production of specific antibodies.
AB  - Cathepsin B (EC 3.4.22.1) has been highly purified (14,225 fold) from bovine
      kidney by a rapid procedure that included the preparation of an enriched
      lysosomal extract, a selective fractionation with ammonium sulphate, size
      exclusion chromatography, two cation-exchange chromatographies, and anion
      exchange chromatography on diethylaminoethyl-Sephacel. After the last
      purification step, two hydrolytic peaks against Z-Phe-Arg-AMC were separated from
      each other, a minor peak corresponding to the cathepsin B single-chain form and a
      major one representing the double-chain form of cathepsin B. The single-chain
      form showed a molecular mass of 31 kDa on sodium dodecyl sulphate -
      polyacrylamide gel electrphoresis (PAGE) under reducing conditions, whereas the
      heavy chain of the double-chain form appeared as a doublet with molecular masses
      of 23.4 and 25 kDa, respectively. The identity of the different cathepsin B
      isoforms and the quality of the final enzyme preparation were confirmed by using
      two types of antibodies, one against a synthetic peptide sequence and one against
      purified cathepsin B. The proteomic study confirmed the identity of the different
      SDS-PAGE protein bands as cathepsin B isoforms and allowed the comparison and
      study of some structural differences between them at the level of their primary
      structures.

PMID- 14569306
TI  - [Neuropsychological tools for the study of depression].
AB  - Depression is a common disorder, affecting approximately one in ten of the
      population at some time in their lives. The nature and extent of such changes,
      however, is less clear, and their specificity to mood disorder, their existence
      before the onset of affective symptoms, their etiology and their relation ship to
      underlying neuroanatomical abnormalities remain poorly understood. Our objective
      is to present a comprehensive review of the existing neuropsychological
      literature on bipolar affective disorder, mayor depression and the differential
      diagnosis between geriatric depression and the depression as early symptom of
      Alzheimer's disease. The most critical neuropsychological assessment to study
      this patients will be discussed. Depression is associated with dysexecutive
      syndrome which correlate with fronto subcortical diseases. Cognitive impairment
      include attention disorders, memory difficulties type forgetfulness and executive
      dysfunction (planning and executions of complex behaviors, monitoring of
      performance, feedback, decision making etc). Cortical neuropsychological profile
      in a depressive patients represent Alzheimer's disease associate.
      Neuropsychological assessment is useful to detect both different cognitive
      profiles (Cortical vs Subcortical).

PMID- 14569307
TI  - [Suicidal behavior in adolescents. Risk factors (bibliography review and
      descriptive-analytical study)].
AB  - In the United States suicide is the third cause of death among adolescents.
      Suicidal behavior has increased a hundred percent over the last three decades; it
      is one of the most frequent psychiatric emergencies and the first cause of
      admission among inpatients between 15 and 24 years. OBJECTIVE: This paper is
      divided in two parts. The first one is made up of a review about risk factors for
      suicidal behavior in adolescents. The objective of the second part study is to
      estimate the frequency of risk factors for suicidal behavior in a sample of
      inpatients and to correlate them with high lethality suicidal attempts. METHOD:
      This is a retrospective, observational, descriptive, analytic transversal study
      based on information from 23 medical records. Variables were processed by
      bivariated analysis; relative risk was obtained considering high lethality
      suicidal attempt as dependent variable. RESULTS: Statistically significant
      relationships were found between high lethality suicidal attempt and no Axe II
      diagnosis and with the appearance of hopelessness. DISCUSSION: Suicidal attempts
      in adolescents with an Axe II diagnosis could be more related to self-harming
      than to a wish to die. Hopelessness can be considered an independent variable
      that determines the lethality of the suicidal attempt.

PMID- 14569308
TI  - [Prodromic aspects of schizophrenia].
AB  - The prodroms in schizophrenia have been discussed even before Eugene Bleuler's
      definition of this group of psychosis. In the last years, the psychiatrists have
      been interested in this subject again. In this article the author presents a
      historical review of the scientific literature about this clinical problem in
      order to improve our understanding of this difficult issue.

PMID- 14569309
TI  - [Early diagnosis of schizophrenic psychosis].
AB  - Schizophrenia is an illness characterized by its syndromic polimorphism and a
      global impairment of personality traits, that means a lot of suffering for
      patients and their families. Lately, under the framework of the
      "neurodevelopmental theory of schizophrenia", the scientific community has paid
      attention to the need of detecting the illness before onset or as soon as
      possible. The study of premorbid personality traits, as "schizotaxia" or schizoid
      or schyzotypal personality, altogether with the study of the so called "basic
      symptoms" an premorbid states are designed to detect at risk subjects. The need
      of not waiting until acute onset syndromes in an attempt to more early
      interventions, due to the fact that there is strong evidence about the existence
      of early symptoms which proper identification will allow, in the future, to
      identify subjects at risk an earlier interventions. In this paper we will review
      only some of the great number of papers recently published on the subject.

PMID- 14569310
TI  - [Neurological soft signs in schizophrenia].
AB  - Neurological Soft Signs (NSS) are defined as potential biological markers for
      schizophrenic disorders. There has recently been a renewer interest in its study.
      These NSS are not related to localized brain lesions, but it has been
      hypothesized that they reflect abnormalities in motor, sensory and integrative
      functions. It has been reported that schizophrenic patients exhibit NSS years
      before of the onset of psychotic symptoms and that they remain after recovery of
      that symptoms. Environmental and genetic causes have been involved in their
      origin. Different assessment scales have been developed in order to allow for
      comparisons between different studies and for relating NSS to clinical,
      psychopathological, neurocognitive, social and demographical variables of the
      disease. It has been demonstrated their relative independence of treatment and
      evolution of the disease.

PMID- 14569311
TI  - [Early markers of schizophrenia. Will we be able to predict the illness?].
AB  - The study of early markers of schizophrenia can help us to develop etiological
      explanations as well as early therapeutic interventions. In this study we review
      retrospective studies, follow-up studies of population cohorts and follow-up
      studies of persons at high genetic risk for schizophrenia. These studies show
      that, in general, we can observe motor abnormalities since the very early
      childhood that later become silent. On the other hand, cognitive abnormalities
      begin at childhood and persist throughout adolescence. Sociability abnormalities
      are shown after puberty. Due to the low specificity of these early precursors, we
      can not efficiently predict schizophrenia yet. However, any measure that improves
      common precursors of different illnesses will have favorable consequences.

PMID- 14569312
TI  - [The meaning of obsessive features of personality in the vulnerability and
      prognosis of schizophrenia].
AB  - In this study on schizophrenia, we raise the issue of the existing relation
      between negative symptoms (also called symptoms of deficiency) cognitive
      impairment attributed to the illness and personality features, in a population of
      chronically ill, long-term hospitalized men. We found obsessive personality
      features were present in the group of patients which presented fewer signs of
      deficiency and cognitive impairment. The presence of these features constitutes
      an important element in the evaluation of prognosis and vulnerability to suffer
      the illness. Therefore, further studies should be carried out to confirm the
      possibility that obsessive features, act as a factor of protection from cognitive
      impairment and negative symptoms of deficiency.

PMID- 14569313
TI  - [Benedict Augustin Morel and the origin of the term dementia praecox].

PMID- 14569314
TI  - [Clinical study of mental diseases (fragments). 1851-1852].

PMID- 14569315
TI  - [The promise of science. The power to cure. 156 Annual Congress of the American
      Psychiatry Association (APA)].

PMID- 14569316
TI  - Low antioxidant content and mutation load in mitochondrial DNA A3243G mutation
      related diabetes mellitus.
AB  - BACKGROUND AND PURPOSE: Diabetes mellitus (DM) is a common clinical manifestation
      in patients harboring mitochondrial encephalomyopathy, lactic acidosis with
      stroke-like episodes (MELAS)-specific A3243G mitochondrial DNA (mtDNA) mutation.
      However, in some MELAS family members, the presence of mtDNA mutation in the
      blood is not always associated with DM, and the relationship between development
      of DM and A3243G mtDNA mutation is not fully understood. This study evaluated the
      relationship between A3243G mtDNA mutation and DM in a Taiwanese family. METHODS:
      We analyzed the relation of genotypic and phenotypic characteristics in a 2
      generation DM family associated with the A3243G mtDNA mutation. The contents of
      mutant mtDNA in various tissue samples of 11 family members and their serum
      levels of antioxidants, including protein thiols and alpha-tocopherol (vitamin E)
      were determined and correlated with their past history and various clinical
      manifestations. RESULTS: DM in 4 members of the first and second generations was
      associated with age and decreased serum levels of antioxidant protein thiols. In
      a series of studies of mutant mtDNA content in various tissues, a relatively low
      proportion of A3243G mutant mtDNA was noted in the elderly proband and her
      elderly symptomatic siblings. A low proportion of mutant mtDNA was also noted in
      a younger family member presenting with DM. Moreover, a significantly lower
      average level of protein thiols was found in the symptomatic family members
      compared to the asymptomatic members (2.3 +/- 0.2 vs 3.5 +/- 0.54 nmol/mg
      protein, p < 0.05). CONCLUSIONS: The finding of relatively lower levels of mutant
      mtDNA in the elderly proband and her elderly symptomatic family members indicates
      that DM may be a late phenotypic expression in patients harboring MELAS-specific
      mtDNA mutation. Decreased serum protein thiols, suggestive of increased oxidative
      stress, also appear to be an early sign associated with subsequent development of
      DM.

PMID- 14569317
TI  - Trends in asthma mortality in Taiwan, 1981-2000.
AB  - BACKGROUND AND PURPOSE: The prevalence and mortality rates of asthma in many
      countries have increased in the past 2 decades. The purpose of this study was to
      determine the trends of asthma mortality in Taiwan from 1981 through 2000.
      METHODS: Data from the National Health Statistics for Taiwan identifying asthma
      [International Classification of Disease (ICD)-9 code 493] as the underlying
      cause of death were collected. Age-specific and age-adjusted mortality rates of
      asthma were calculated and the 20-year trends were analyzed. RESULTS: The crude
      mortality rate of asthma decreased from 8.17 to 4.53 per 100,000 general
      population, and the age-adjusted mortality rate decreased from 8.17 to 2.37 per
      100,000 during the 20-year period. This trend of decreasing mortality was most
      obvious for age groups older than 35 years, i.e., from 4.05 to 1.20 per 100,000
      in those aged 35 to 54 years and from 47.43 to 13.44 per 100,000 in those aged 55
      to 74 years. The mortality rate for asthma in those aged 15 to 34 years remained
      the same, around 0.40 to 0.35 per 100,000 population. For those below 15 years of
      age, the mortality rates for asthma fluctuated between 0.30 and 0.10 per 100,000
      population. CONCLUSIONS: The mortality rate of asthma has steadily decreased in
      Taiwan in the past 20 years, especially in the age groups above 35 years.

PMID- 14569318
TI  - Prediction of arterial blood gas values from venous blood gas values in patients
      with acute respiratory failure receiving mechanical ventilation.
AB  - BACKGROUND AND PURPOSE: Arterial blood gas (ABG) analysis is useful in evaluation
      of the clinical condition of critically ill patients; however, arterial puncture
      or insertion of an arterial catheter may cause many complications. This study
      evaluated whether pH, partial pressure of carbon dioxide (PCO2) and bicarbonate
      (HCO3-) values of venous blood gas (VBG) could accurately predict their ABG
      analogs for patients with acute respiratory failure treated by mechanical
      ventilation in an intensive care unit (ICU). METHODS: Forty six patients who were
      admitted to the ICU due to acute respiratory failure and treated by mechanical
      ventilation were included in this study. Blood for VBG analysis was sampled from
      the cubital or dorsal palmar veins, while ABG was sampled simultaneously from the
      radial or brachial arteries via an arterial catheter at the other upper
      extremity. Regression equations and mean percentage-difference equations were
      derived to predict arterial pH, PCO2, and HCO3- values from their VBG analogs.
      The equations were validated by evaluating VBG and ABG samples from a separate
      group of 11 patients. RESULTS: A total of 46 paired samples from 46 patients were
      evaluated. The mean percentage differences between the venous and arterial values
      divided by venous values for pH, PCO2, and HCO3- were (mean +/- SD): deltapH (%),
      0.50 +/- 0.45; deltaPCO2 (%), 17.09 +/- 9.60; and deltaHCO3- (%), 9.72 +/- 7.73;
      respectively. Regression equations for prediction of pH, PCO2 and HCO3- values
      were: arterial pH (pHa) = 0.45 + 0.94 x venous pH (pHv) [r = 0.83, p < 0.0001];
      partial pressure of arterial CO2 (PaCO2) = 3.06 + 0.76 x partial pressure of
      venous CO2 (PvCO2) [r = 0.86, p < 0.0001]; and arterial HCO3- (HCO3-a) = 2.34 +
      0.82 x venous HCO3- (HCO3-v) [r = 0.91, p < 0.0001]. The predicted ABG values
      from the mean percentage-difference equations were derived as follows: pHa = pHv
      x 1.005; PaCO2 = PvCO2 x 0.83; and HCO3-a = HCO3-v x 0.90. Validation of the
      regression equations and mean percentage-difference equations revealed only a
      small (clinically insignificant) variation between the actual and predicted ABG
      values. CONCLUSIONS: Venous blood gas can accurately predict the ABG values of
      pH, PCO2 and HCO3- for patients with acute respiratory failure being treated with
      mechanical ventilation.

PMID- 14569319
TI  - Nutritional predictors of survival in terminally ill cancer patients.
AB  - BACKGROUND AND PURPOSE: Malnutrition can affect the prognosis of terminally ill
      patients, but over-treatment of malnutrition can worsen patients' quality of
      life. Decisions on nutrition and the supply of fluids to terminally ill patients
      are complex, and the identification of useful clinical indicators is needed. This
      study evaluated the relationships between various nutritional indices and
      survival of terminally ill cancer patients. METHODS: We recruited terminally ill
      patients from a teaching hospital between February 2000 and January 2001. All of
      the 145 candidates were cancer patients, 109 (75%) of whom agreed to participate.
      Nutritional assessments including physical examination, anthropometric
      measurements, and biochemical profiles were performed on admission. RESULTS:
      Univariate analyses showed that triceps skin-fold thickness (TSF) and midarm
      muscle circumference were significant predictors of survival. Poor survival was
      associated with prealbumin </= 100 mg/L (hazard ratio [HR], 1.5; 95% confidence
      interval [CI], 1.1 to 2.3; p = 0.03), asparate transaminase (AST) > 45 U/L (HR,
      1.6; 95% CI, 1.1 to 2.3; p = 0.03), alkaline phosphatase > 120 U/L (HR, 1.6; 95%
      CI, 1.1 to 2.5; p = 0.02), creatinine > 1.4 mg/dL (HR, 1.9; 95% CI, 1.2 to 3.2; p
      = 0.01), and blood urea nitrogen (BUN) > 20 mg/dL (HR, 1.9; 95% CI, 1.3 to 2.8; p
      < 0.01) at admission. Multivariate analyses found that TSF < 25% of the nomogram
      (HR, 2.9; 95% CI, 1.6 to 5.3; p < 0.01), prealbumin </= 100 mg/L (HR, 2.2; 95%
      CI, 1.4 to 3.5; p < 0.01), AST > 45 U/L (HR, 2.0; 95% CI, 1.3 to 3.2; p = 0.01),
      and BUN > 20 mg/dL (HR, 2.8; 95% CI, 1.7 to 4.5; p < 0.01) were independent
      predictors of poor survival. CONCLUSIONS: This study found that nutritional
      status was associated with the survival of terminally ill cancer patients. Both
      TSF and prealbumin appeared to be useful predictors that may help set strategies
      to improve palliative care. Because predictors of survival are not necessarily
      factors that actually influence survival, further studies should be conducted to
      evaluate the usefulness of these prognostic indicators in clinical practice.

PMID- 14569320
TI  - Effectiveness of alpha1-adrenergic blockers in boys with low urinary flow rate
      and urinary incontinence.
AB  - BACKGROUND AND PURPOSE: Although alpha blockers have been shown to be effective
      in treating various types of neuropathic voiding dysfunction in children, the
      effectiveness of alpha(1) blockers in treating neurologically intact children
      with voiding dysfunction remains unclear. We investigated the effectiveness of
      treatment with alpha(1)-adrenergic blockade in boys with low uroflow rate and
      urinary incontinence. METHODS: The alpha(1) blocker doxazosin (0.5 to 1.0 mg
      daily) was administered to 16 boys (mean age, 8.9 +/- 3.4 years) with maximum
      uroflow rate (Qmax) < 15 mL/s and urinary incontinence. Uroflowmetry and postvoid
      residual volumes were checked before and 4 weeks after doxazosin treatment. After
      discontinuation of doxazosin for 2 weeks, videourodynamics and cystoscopy were
      done in 12 of the 16 boys. Improvement of uroflow was arbitrarily defined as an
      increase of Qmax >/= 2.5 mL/s. Complete improvement of incontinence was defined
      as > 90% and partial improvement as 50 to 90% reduction of incontinence episodes.
      Successful treatment was defined as improvement in uroflow and partial or
      complete improvement of urinary incontinence. Blood pressure, first-dose
      phenomenon, and adverse effects were monitored at each visit. RESULTS: Mean
      medication and follow-up periods were 24.5 weeks and 33.1 weeks, respectively.
      Improvement of uroflow was noted in 10 patients (63%). Qmax increased from 12.3
      +/- 1.3 mL/s to 16.3 +/- 4.1 mL/s (p = 0.001). Complete and partial improvement
      of incontinence was noted in 7 and 3 patients, respectively. The mean number of
      wet nights per week decreased from 4.9 +/- 2.3 to 2.2 +/- 2.5 (p < 0.001).
      Successful treatment was noted in 8 boys (50%), including 3 of 5 boys with
      primary bladder neck obstruction, 3 of 4 boys with dysfunctional voiding, and 2
      of 4 boys with neuropathic voiding dysfunction of unclassified etiology. There
      were no significant adverse effects. Decreases of systolic and diastolic blood
      pressure were negligible. CONCLUSION: alpha(1) Blockade is effective in the
      treatment of boys with low uroflow rate and incontinence.

PMID- 14569321
TI  - Comparison of outcome of off-pump coronary artery bypass surgery and conventional
      coronary artery bypass surgery.
AB  - BACKGROUND AND PURPOSE: Off-pump coronary artery bypass grafting (CABG) [OPCAB]
      is preferred to conventional CABG with cardiopulmonary bypass (CPB) for many
      specific subgroups, such as elderly patients and high-risk patients. Whether
      OPCAB should be the first choice of surgical procedure for a wider range of
      coronary artery disease patient subgroups remains controversial. The purpose of
      this study was to compare the clinical results of OPCAB and CPB in our hospital.
      METHODS: We retrospectively analyzed the results for 404 patients who received
      OPCAB or CPB between March 2000 and December 2001. Surgical methods adopted were
      at the discretion of the attending surgeon. In addition, subgroups of patients
      were analyzed to assess whether or not OPCAB was more successful in patients with
      specific characteristics. RESULTS: There were no significant differences in the
      demographic data between the 2 groups. The perioperative mortality rate was
      similar for the CPB and OPCAB groups (2.5% and 2.0%, respectively; p = 1.00.)
      OPCAB was superior with respect to inotropic use, postoperative bleeding amount,
      transfusion amount, and length of intensive care unit and hospital stay (p < 0.05
      for all), and also had a lower incidence of re-entry due to bleeding (6.7% vs
      13.6%, p = 0.04) and prolonged hospitalization > 30 days (1.5% vs 10.8%, p <
      0.01). At 12 months' follow-up, the OPCAB group had a lower rate of mortality
      (1.5% vs 5.6%, p = 0.03) and a comparable rate of readmission for cardiac reasons
      (6.6% vs 9.6%, p = 0.28). The rate of poor in-hospital outcome was lower in the
      OPCAB than in the CPB group (3.0% vs 13.3%, p </= 0.01), while the percentage
      with poor results on follow-up was comparable between the 2 groups (7.1% vs
      12.1%, p = 0.09). In addition, subgroups defined as: female, age > 65 years, age
      < 65 years, diabetes, peripheral arterial occlusive disease, end-stage renal
      disease, left ventricular ejection fraction < 50%, preoperative intra-aortic
      balloon pump use, and left-main disease had better in-hospital outcome in the
      OPCAB group compared with the CPB group, while no subgroups had worse in-hospital
      outcomes with OPCAB. The 12-month follow-up outcome was similar with the 2
      techniques. CONCLUSION: Use of OPCAB in CABG operation was associated with
      improved in-hospital outcome and similar follow-up outcome compared to CPB. No
      subgroup had a worse outcome with OPCAB.

PMID- 14569322
TI  - Features of severe pneumonia in patients with undiagnosed pulmonary tuberculosis
      in an intensive care unit.
AB  - BACKGROUND AND PURPOSE: Early antituberculosis (anti-TB) therapy in hospitalized,
      severely ill patients with pulmonary tuberculosis (PTB) diminishes the mortality
      and morbidity rate and also reduces nosocomial transmission. However, delayed
      diagnosis of PTB is common in the respiratory intensive care unit (RICU),
      especially in patients with respiratory failure. This retrospective study
      evaluated the clinical features of RICU patients with severe pneumonia and
      undiagnosed active PTB, in order to determine which specific features might help
      in the screening of these patients. METHODS: Patients with severe pneumonia with
      undiagnosed active PTB and those without active PTB on admission to the RICU,
      from March 1, 2000 to August 31, 2002, were compared. The 2 groups of patients
      were matched for age, gender, and Acute Physiology and Chronic Health Evaluation
      (APACHE) II score prior to the analysis. Data on clinical course, chest
      radiographic patterns, and laboratory findings were collected. RESULTS: Thirty
      five patients in the case group were matched with 35 controls who were similar
      with regard to age, gender, smoking history, acute lung injury score, and the
      presence of underlying disease. The duration of symptoms before admission was
      significantly longer in the case group than in the control group (15.1 +/- 13.9
      vs 7.8 +/- 7.6 days, p = 0.012). The mean interval from admission to the RICU to
      the initiation of anti-TB therapy was 10.0 +/- 9.8 days. Small nodular lesions (p
      = 0.044) and cavitary lesions (p = 0.013) predominated on the chest radiograph in
      the case group. The mortality rates at discharge were not significantly different
      between the case group and the control group. CONCLUSIONS: These data suggest
      that when a patient developing severe pneumonia has a history of a sub-acute or
      chronic illness longer than 2 weeks in duration, and predominant small nodular or
      cavitary patterns on chest radiograph, active PTB should be considered.

PMID- 14569324
TI  - Coronary stent graft for hypertrophic obstructive cardiomyopathy combined with
      coronary artery disease.
AB  - Percutaneous transluminal coronary angioplasty and stenting are established
      therapeutic modalities for coronary artery disease (CAD). Percutaneous
      transluminal septal myocardial ablation has become increasingly important for the
      treatment of symptomatic patients with hypertrophic obstructive cardiomyopathy
      (HOCM). We report a case of HOCM combined with CAD involving the left anterior
      descending coronary artery. Coronary stent graft implantation was performed with
      uneventful recovery. Coronary stent graft implantation may be beneficial in
      selected cases of symptomatic HOCM combined with CAD.

PMID- 14569323
TI  - Sirolimus-induced interstitial pneumonitis in a renal transplant recipient.
AB  - Sirolimus is a recently licensed immunosuppressant for organ transplantation that
      has been used as basic, adjuvant, or maintenance therapy for prevention of organ
      rejection. Well-known side effects of this agent are hyperlipidemia and bone
      marrow suppression. Interstitial pneumonitis is a relatively newly described
      adverse effect of the drug. A 43-year-old female recipient of a cadaveric kidney
      developed cough with blood-tinged sputum while receiving sirolimus
      immunosuppressive therapy. High-resolution computed tomographic scan and chest
      radiograph revealed interstitial infiltrations over bilateral lower lungs. No
      evidence of bacterial, fungal, mycobacterial, or viral infection was found and
      all tests for collagen vascular diseases were negative. Discontinuation of
      sirolimus resulted in a significant improvement of the lung disease.

PMID- 14569325
TI  - Successful pulmonary thromboendarterectomy in a patient with subacute pulmonary
      thromboembolism.
AB  - Pulmonary thromboembolism can lead to serious hemodynamic instability or even
      death. Treatment for subacute pulmonary thromboembolism is not standardized. We
      report a case of subacute pulmonary thromboembolism successfully treated by
      pulmonary thromboendarterectomy. A 63-year-old woman without underlying disease
      was admitted due to progressive shortness of breath with episodic exacerbation
      for more than 5 months. Hypoxemia was noted on admission. Contrast-enhanced
      spiral computed tomography of the chest revealed multiple thrombi in the central
      pulmonary arteries. Pulmonary thromboendarterectomy was performed 5 days after
      admission. The surgical specimens showed acute, subacute, and chronic stages of
      thrombi. Her clinical condition improved markedly after operation. She was
      discharged and had recovered fully at follow-up 6 months after discharge. This
      case suggests that pulmonary thromboendarterectomy may be beneficial for patients
      with subacute pulmonary thromboembolism.

PMID- 14569326
TI  - Surgical treatment for thoracic spine fracture-dislocation without neurological
      deficit.
AB  - Complete fracture-dislocation of the thoracic spine is a rare injury resulting
      from high-energy impaction that commonly presents with severe neurological
      deficit. We report a case of this condition in a patient who was involved in a
      motorcycle-vehicle collision, that resulted in multiple trauma and complete
      fracture-dislocation of the T7-T8 with middle column-posterior column
      dissociation. A posterior approach was used for decompression and immediate
      stabilization of this severe, unstable injury, combined with an anterior approach
      for anatomic reduction and intervertebral body fusion. No neurological
      complications occurred either preoperatively or postoperatively.

PMID- 14569327
TI  - Nodular fasciitis: clinical characteristics and preoperative diagnosis.
AB  - BACKGROUND AND PURPOSE: Because of its rapid growth, hypercellularity, and brisk
      mitotic rate, nodular fasciitis (NF) is probably the most common benign
      mesenchymal tumor that is misdiagnosed as a sarcoma, often leading to unnecessary
      and overly aggressive therapy. METHODS: This retrospective study evaluated the
      characteristics of 92 well-documented cases of NF treated from 1988 to 2001.
      Gender, age, location, size, and clinical symptoms were analyzed, as was the
      accuracy of preoperative diagnosis. RESULTS: Females were predominant (male-to
      female ratio, 1:1.71; p = 0.006, binomial distribution). Accurate preoperative
      diagnosis was made in only 14.1%, but this rate improved in recent years (p =
      0.034, chi-squared test for trend). The pathologic subtype of NF did not
      correlate with the duration of the lesion. CONCLUSIONS: Clinicians should include
      NF in the differential diagnosis of rapidly growing subcutaneous tumors and not
      rush to overly aggressive therapy.

PMID- 14569328
TI  - [Factors associated with HIV risk perception among hospital postpartum women].
AB  - OBJECTIVE: To assess factors associated with perception of HIV infection risk
      among postpartum women admitted to charitable maternity hospitals. METHODS: The
      study sample comprised 384 postpartum women admitted to two charitable maternity
      hospitals in the city of Sao Paulo, Brazil. Data collection was carried out from
      January to March 2000. All women were interviewed 12 hours after delivery and
      data was collected on sociodemographics, STD/AIDS knowledge and attitudes
      (independent variables) and cultural issues (dependent variables), and "whether
      she considered herself at risk for HIV infection" (dependent variable).
      Statistical analysis was performed using Chi-square test and multiple logistic
      regression. RESULTS: Nearly 29% of postpartum women considered themselves at risk
      for HIV infection. They were single, had prior STD and believed "married men
      enjoy himself in the same way as single men do". Prevention and health
      maintenance behaviors were also identified. CONCLUSIONS: Women's knowledge on
      AIDS seems to affect their individual risk perception. Future HIV/AIDS prevention
      campaigns should be focused on increasing couples and adolescents' involvement.

PMID- 14569329
TI  - Voluntary HIV counseling and testing during prenatal care in Brazil.
AB  - OBJECTIVE: Voluntary HIV counseling and testing are provided to all Brazilian
      pregnant women with the purpose of reducing mother-to-child HIV transmission. The
      purpose of the study was to assess characteristics of HIV testing and identify
      factors associated with HIV counseling and testing. METHODS: A cross-sectional
      study was carried out comprising 1,658 mothers living in Porto Alegre, Brazil.
      Biological, reproductive and social variables were obtained from mothers by means
      of a standardized questionnaire. Being counseling about HIV testing was the
      dependent variable. Confidence intervals, chi-square test and hierarchical
      logistic model were used to determine the association between counseling and
      maternal variables. RESULTS: Of 1,658 mothers interviewed, 1,603 or 96.7% (95%
      CI: 95.7-97.5) underwent HIV testing, and 51 or 3.1% (95% CI: 2.3-4.0) were not
      tested. Four (0.2%) refused to undergo testing after counseling. Of 51 women not
      tested in this study, 30 had undergone the testing previously. Of 1,603 women
      tested, 630 or 39.3% (95% CI: 36.9-41.7) received counseling, 947 or 59.2% (95%
      CI: 56.6-61.5) did not, and 26 (1.6%) did not inform. Low income, lack of
      prenatal care, late beginning of prenatal care, use of rapid testing, and
      receiving prenatal in the public sector were variables independently associated
      with a lower probability of getting counseling about HIV testing. CONCLUSIONS:
      The study findings confirmed the high rate of prenatal HIV testing in Porto
      Alegre. However, women coming from less privileged social groups were less likely
      to receive information and benefit from counseling.

PMID- 14569330
TI  - [Characteristics of adolescent pregnancy in Sao Luis, Maranhao, Brazil].
AB  - OBJECTIVE: To identify the main socioeconomic, demographic, anthropometric and
      behavioral characteristics, and pregnancy outcomes of adolescent pregnancy and to
      assess health services used by pregnant adolescents. METHODS: Data were collected
      from a cross-section of 2,429 deliveries by women residing in the municipality of
      Sao Luis, Brazil, of which 94% were hospital births. Women were categorized into
      six age groups. The two groups of teenagers (under 18 and 18-19 years) were
      compared to four groups of older women. Comparison was also made between the two
      teenage groups. The chi-square test was used to compare proportions and
      prevalence ratio was used as an effect measure. RESULTS: Of 2,429 women, 714
      (29.4%) were adolescents. Their specific fertility coefficient was higher than in
      other regions of the country. Adolescents showed lower socioeconomic and
      reproductive conditions than older women and a higher proportion of inadequate
      prenatal care. The majority had no partner. They had the lowest percentages of
      caesarean section and smokers. CONCLUSIONS: Despite their equally unfavorable
      socioeconomic situation, 18-19 year-old adolescents had pregnancy outcomes
      comparable to the age group 25-29, whereas those under 18 had the highest
      proportions of low birth weight, preterm birth, and infant mortality rate. This
      suggests that biologic immaturity may be associated with adverse pregnancy
      outcomes.

PMID- 14569331
TI  - [Contraceptive use among adolescents at public schools in Brazil].
AB  - OBJECTIVE: There has been a growing interest in patterns of contraceptive use
      among adolescents, due, in particular, to the social relevance attached to
      pregnancy in this age group. Therefore, the objective of the study was to
      investigate factors associated with the use of contraceptive methods among female
      and male adolescent students. METHOD: A cross-sectional study was conducted, by
      means of self-applied questionnaires, among 4,774 students ranging from 11 to 19
      years of age. Prevalence with respect to the use of contraceptive methods during
      the first experience of sexual intercourse as well as the most recent one was
      calculated both separately, that is, for each of these events, and in conjunction
      as a measure of consistent use. Logistic regression was carried out for
      simultaneous analysis of factors associated with the use of contraceptive methods
      and in order to calculate adjusted measures. RESULTS: Among the 1,664 students
      who reported being sexually active, the factors positively associated with the
      consistent use of contraceptive methods among male students included a)
      postponing their first experience of sexual intercourse and interaction with a
      stable partner, b) the family as a potential supplier of contraceptive methods,
      and c) access to health services. On the other hand, among female students
      factors positively associated with the consistent use of contraceptive methods
      included a) recent sexual initiation, and b) having a father as their source of
      information regarding sexuality, contraception and STD/AIDS prevention. Pregnancy
      was reported by 6.4% of the boys and 18.1% of the girls, its absence was
      associated with the consistent use of contraceptives by them (the girls) (Odds
      Ratio=3.83; 2.06-7.15). CONCLUSIONS: The results confirm the complexity of
      determining contraceptive behavior among adolescents and therefore reinforce the
      need to include multi-dimensional aspects of this theme in order to ensure the
      efficacy of sex education programs.

PMID- 14569332
TI  - [Knowledge, attitude and practice of breast self-examination in health centers].
AB  - OBJECTIVE: Breast cancer is one of the most important problems of public health
      and education regarding breast self-examination is one of the important steps for
      identifying breast tumors at an early stage. The present study was carried out to
      assess knowledge, attitude, and practice of breast self-examination among
      patients attending health centers. METHODS: In a KAP (Knowledge, Attitude and
      Practice) survey 663 women of 13 randomly selected municipal health centers were
      interviewed. The number of interviews in each health center was proportional to
      the mean number of women seen per month. In the data analysis, women's answers
      for knowledge, attitude and practice regarding breast self-examination were
      classified according to their adequacy as previously defined. Adequacy was
      compared among categories of control variables with Chi2 test. RESULTS: The
      results showed that knowledge and practice of breast self-examination were
      adequate in 7.4% and 16.7%, respectively. However, attitude was adequate in 95.9%
      of the women interviewed. The study also showed that 58.1% of the women
      interviewed referred that forgetfulness was the main barrier for not performing
      self-examination. CONCLUSIONS: Women attending the health centers sampled in this
      study had inadequate knowledge and practice about breast self-examination but
      they had an adequate and favorable attitude about it.

PMID- 14569333
TI  - [Knowledge adequacy on contraceptives among women in Campinas, Brazil].
AB  - OBJECTIVE: An analysis of secondary data was carried out to evaluate the
      knowledge adequacy on contraceptives and its association with socioeconomic and
      demographic characteristics. METHODS: The sample consisted of 472 women from the
      city of Campinas, state of Sao Paulo, Brazil. Chi-square test was used to
      evaluate differences among variables and logistic regression was performed to
      identify independent variables associated with knowledge adequacy (evaluated
      through a score). RESULTS: Of the total, 47.6% women reached a score higher than
      six, which was classified as an adequate knowledge on contraceptives. Higher
      schooling and better socioeconomic status were associated to higher scores of
      knowledge. CONCLUSIONS: The results show that it is necessary to improve women's
      education in general, and on contraceptive methods specifically. In addition,
      professionals working in public health services should be capacitated to provide
      contraceptives as well as adequate information on contraceptive methods.

PMID- 14569334
TI  - [Comparison between different mortality risk scores in a neonatal intensive care
      unit].
AB  - OBJECTIVES: To evaluate and compare birthweight and scores as predictors of
      neonatal mortality in a Neonatal Intensive Care Unit (NICU). METHODS: The survey
      included 494 newborns admitted to the neonatal intensive care unit (NICU) of a
      general hospital in Porto Alegre, southern Brazil, immediately after delivery,
      between March 1997 and June 1998. Birthweight and scores were evaluated in terms
      of the variable "death while in NICU". Exclusion criteria were: discharge or
      death less than 24 hours after admission, admission not immediately following
      delivery, incomplete study protocol, and congenital malformations incompatible
      with survival. For CRIB (Clinical Risk Index for Babies) evaluation purposes,
      only patients born weighing up to 1,500 g were considered. ROC (Receiver
      Operating Characteristics) curves were calculated for SNAP (Score for Neonatal
      Acute Physiology), SNAP-PE (Score for Neonatal Acute Physiology--Perinatal
      Extension), SNAP II, SNAP-PE II, and CRIB scores, as well as for birthweight.
      RESULTS: Of the 494 patients studied, 44 died (8.9% mortality). Of the 102
      patients born weighing up to 1,500 g, 32 (31.3%) died. The area below the ROC
      curves ranged from 0.81 to 0.94. There were no statistically significant
      differences between the areas obtained for all scores evaluated. All mortality
      risk scores evaluated performed better than birthweight, especially on newborns
      with birthweight=1,500 g. CONCLUSIONS: All neonatal mortality scores had better
      performance and were superior to birthweight as measures of in-hospital mortality
      risk for newborns admitted to NICU.

PMID- 14569335
TI  - [CRIB score, birth weight and gestational age in neonatal mortality risk
      evaluation].
AB  - OBJECTIVE: To evaluate the mortality rate of very low birth weight babies born at
      a Neonatal Intensive Care Unit (NICU) during a specified period of time according
      to variations in CRIB (Clinical Risk Index for Babies) score, birth weight and
      gestational age. METHODS: From January 1997 to December 2000, the CRIB score was
      prospectively applied to all newborn infants admitted to the NICU of an
      university hospital of Londrina, Brazil, with birthweight under 1,500 g and/or
      gestational age of less than 31 weeks. The exclusion criteria were: death before
      12 hours of life, presence of lethal congenital malformations and newborns who
      had been referred from other hospital. RESULTS: Two hundred and eighty-four
      infants met the inclusion criteria. Mean birth weight was 1,148 +/- 248 g
      (median=1,180), mean gestational age was 30.2 +/- 2.4 weeks (median=30.0) and
      mean CRIB score was 3.8 +/- 4.4 (median=2.0). The neonatal mortality rate was
      23.2%, varying according to mean birthweight <750 g (72.7%), gestational age <29
      weeks (57.1%) and CRIB score >10 (79.4%). Receiver Operating Characteristic (ROC)
      curves were composed for CRIB score, birth weight and gestational age to assess
      the ability of each to predict hospital mortality and the areas under the curve
      were respectively 0.88, 0.76 and 0.81. Sensitivity, specificity and predictive
      values were evaluated and all variables were considered predictors of mortality
      (p<0.0001). The optimal cut off point based on the ROC curve for the CRIB score
      was 4 with sensitivity 75.8%, specificity 86.7, positive predictive value 63.3%
      and negative predictive value 92.2%. CONCLUSIONS: In this study infants with
      birthweight of less than 750 grams, less than 29 weeks gestational age and CRIB
      scores above 10 had higher mortality rates. However, a CRIB score higher than 4
      proved to be a better predictor of mortality when compared to birthweight and
      gestational age.

PMID- 14569336
TI  - Association between child-care and acute diarrhea: a study in Portuguese
      children.
AB  - OBJECTIVE: To quantify the influence of the type of child-care on the occurrence
      of acute diarrhea with special emphasis on the effect of children grouping during
      care. METHODS: From October 1998 to January 1999 292 children, aged 24 to 36
      months, recruited using a previously assembled cohort of newborns, were
      evaluated. Information on the type of care and occurrence of diarrhea in the
      previous year was obtained from parents by telephone interview. The Chi2 and
      Kruskal-Wallis tests were used to compare proportions and quantitative variables,
      respectively. The risk of diarrhea was estimated through the calculation of
      incident odds ratios (OR) and their respective 95% confidence intervals (95% CI),
      crude and adjusted by unconditional logistic regression. RESULTS: Using as
      reference category children cared individually at home, the adjusted ORs for
      diarrhea occurrence were 3.18, 95% CI [1.49, 6.77] for children cared in group at
      home, 2.28, 95% CI [0.92, 5.67] for children cared in group in day-care homes and
      2.54, 95% CI [1.21, 5.33] for children cared in day-care centers. Children that
      changed from any other type of child-care setting to child-care centers in the
      year preceding the study showed a risk even higher (OR 7.65, 95% CI [3.25,
      18.02]). CONCLUSIONS: Group care increases the risk of acute diarrhea whatsoever
      the specific setting.

PMID- 14569337
TI  - Usefulness of corneal esthesiometry for screening diabetic retinopathy.
AB  - OBJECTIVE: To assess the usefulness of corneal esthesiometry for screening
      diabetic retinopathy. METHODS: A cross-sectional study was carried out comprising
      575 patients attending a diabetic retinopathy-screening program in the city of
      Sao Paulo. Corneal esthesiometry was assessed with the Cochet-Bonnet
      esthesiometer. The presence of diabetic retinopathy was detected with indirect
      fundoscopy. The validity of corneal esthesiometry in identifying diabetic
      retinopathy was evaluated by the Receiver Operating Characteristic (ROC) curve.
      RESULTS: Sensitivity and specificity analyses of the corneal esthesiometry for
      detecting the stages of diabetic retinopathy using different cut-offs showed
      values less than 80%. The best indices (72.2% sensitivity and 57.4% specificity)
      were obtained for the identification of patients with proliferative diabetic
      retinopathy. CONCLUSIONS: In the study series, corneal esthesiometry was not a
      good indicator of diabetic retinopathy.

PMID- 14569338
TI  - [Factors related to sickness absenteeism among nursing personnel].
AB  - OBJECTIVE: To analyze short-term leaves among the healthcare staff of a
      university hospital. METHODS: Study population included 965 nursing professionals
      active on 1 January 2000. Leaves up to 30 days in one year were analyzed.
      Sickness leaves (one-year aggregate), service demand, and diagnoses were
      described. Relative risk was estimated through multivariate analysis, using
      negative binomial distribution. RESULTS: About 65% of workers generated 1,988
      appointments, of which 68.6% lead to absence from work. The greatest demand
      occurred among nursing technicians, women, and statutory workers (OR=1.61; 1.47;
      1.53 respectively). Over half the studied population (57.6%) had at least one
      absence. This corresponds to 87.8% of workers who had physician appointments.
      These workers generated a total 1,364 leaves of absence--1.41 per worker--and
      5,279 workdays were missed. Multivariate analysis was carried out considering
      each gender separately. An effect was found only for work regime (RR=1.45 e
      RR=2.43) for both men and women. CONCLUSIONS: A relationship exists between
      absenteeism and work regime. It is necessary to include other variables, such as
      time working for the company, shift, and number of children.

PMID- 14569339
TI  - [PSA and anthropometric measurements among Amazon Indians: an evaluation of the
      Parkateje community].
AB  - OBJECTIVE: PSA (prostate-specific antigen) screening for early detection of
      prostate cancer in a native community is of great epidemiological importance. The
      study was conducted with the objective of verifying the occurrence of prostate
      cancer among members of an Amazon community, as well as its possible relationship
      to acculturation and overweight (body mass index). METHODS: Lifestyle and
      anthropometric information was collected from a group of 22 men, presumedly over
      age 50, members of an isolated community of 363 Amazonian Indians--self
      denominated Parkateje and Kykateje--from Para state, in Northern Brazil. In
      addition to physical and hematological exams, total and free PSA dosages were
      performed. RESULTS: Total PSA serum levels ranged from 0.35 to 25.8 ng/ml. Three
      subjects had PSA levels greater than 4.0 ng/ml, and another two had levels
      between 2.5 and 4.0 ng/ml. Prostate biopsies performed on two subjects indicated
      the presence of prostate adenocarcinoma in one of them and of intraepithelial
      neoplasia on the other. Overweight (BMI> or =25 Kg/m2) and waist-to-hip ratio >
      or =0.9 were observed in 68.1% and 72% of subjects, respectively. CONCLUSIONS:
      Changes in nutritional habits caused by contact with civilization, such as the
      substitution of more caloric foods for the traditional game and vegetable fiber
      are increasing the prevalence of overweight among the community. In view of the
      association between prostate cancer incidence, high-fat diet, and less physical
      activity, it can be assumed that further cases of prostate neoplasia will occur
      in the future, since several community members already have high PSA serum
      levels.

PMID- 14569340
TI  - [Patients who benefit from psychiatric admission in the general hospital].
AB  - OBJECTIVES: Psychiatric hospitalization though burdensome remains a very
      important therapeutic option for severely-ill psychiatric patients.
      Hospitalization in general hospital psychiatry units (GHPU) are often regarded as
      the best option. A study was carried out with the purpose of assessing
      socioeconomic and medical variables associated with success and failure of
      hospitalization. METHODS: A review was performed on sociodemographics and medical
      data of 1,463 patients admitted to a general hospital's GHPU in the period
      between 1986 and 1997. Statistical analysis was conducted using univariate and
      multivariate polythomic logistic regression. RESULTS: In the multivariate
      analysis three factors were identified as associated to poor hospitalization
      outcomes (poor condition at discharge and longer hospital stay): age >60 years,
      poor social functioning, and diagnosis of organic mental disorder. CONCLUSIONS:
      Although 80% of the patients experienced a considerable symptomatic improvement,
      a small group benefited less from hospitalization. It is suggestive that these
      patients would benefit more from psychosocial interventions.

PMID- 14569341
TI  - [Arterial hypertension patients: attitudes, beliefs, perceptions, thoughts and
      practices].
AB  - OBJECTIVE: To get to know arterial hypertension patients through their attitudes,
      beliefs, perceptions, thoughts, and practices related to the disease. METHODS: An
      exploratory study was carried out in 32 hypertensive patients seen at 2 health
      care units in the municipal district of Ribeirao Preto, Brazil. Subjects were
      interviewed in a single session and data were analyzed using the Content Analysis
      method through categories not defined a priori. RESULTS: About half the patients
      (41%) were not able to define hypertension. They believed the main symptoms were
      headaches and neck pain (18%) and the possible consequences of the disease were
      stroke and heart attack (39%). Emotional factors were mentioned as the ones that
      mostly impair hypertension control. To accomplish that, 40% said there should be
      changes in the diet and life style, such as walking and exercising. Regarding
      patients' practices, drug treatment and management by a health provider were most
      often referred. CONCLUSIONS: Psychosocial aspects and health beliefs seem to
      affect directly with patients' knowledge on hypertensive disease and their health
      practices. Given that all patients had already received some kind of information
      about arterial hypertension before the beginning of the study, it would be
      important to propose new forms of educating these patients.

PMID- 14569342
TI  - [Resource distribution for the Basic Care Plan with equity approach, Bogota
      2002].
AB  - OBJECTIVE: To apply a technique that will guide financial resources distribution
      for the Basic Care Plan for carrying out collective actions according to
      different health conditions. METHODS: A prior estimation of a global health index
      was performed by means of the analysis of major components prioritizing areas of
      Bogota according to their health condition: "poor", "intermediate," and "good". A
      square minimum technique was applied to minimize difference between observed and
      expected global health index after resource investment. RESULTS: Resource
      distribution for the Basic Care Plan was achieved for twenty areas of Bogota and
      a higher amount than the district median was allocated in areas with "poor"
      health conditions. Also, areas lacking universal health coverage were identified
      using the per capita resource allocation. CONCLUSIONS: This technique puts in
      evidence the disparity in health conditions between areas of "poor" health
      condition and those with "good" condition, in spite of the increased coverage of
      the Basic Plan of Attention, indicating the need of intersectorial social
      investment in these areas.

PMID- 14569343
TI  - [Ecology of Lutzomyia (Nyssomyia) whitmani in an urban area in Maringa, Parana,
      Brazil].
AB  - OBJECTIVES: To study the fauna, hours of activity and seasonality of
      phlebotomines in forest animal habitats in the Inga Park, on the urban perimeter
      of the municipality of Maringa, Parana State, Brazil. METHODS: Phlebotomines were
      collected on the urban perimeter using Shannon traps from 6:00 p.m. to 6:00 a.m.
      and Falcao traps from 8:00 p.m. to 12:00 midnight, on two nights per month from
      October 1998 to September 2000. The Shannon traps were installed close to forest
      animal habitats and on the banks of the Moscados stream; the Falcao traps were
      placed in shelters for captive birds, forest mammals and reptiles. RESULTS: The
      Shannon traps yielded 13,656 phlebotomines, with predominance of Lutzomyia
      whitmani (98.7%). The Falcao traps yielded 4,040 phlebotomines, with L. whitmani
      again predominating (96.3%). L. whitmani was most frequently found between 12:00
      midnight and 2:00 a.m. in the Shannon traps. This species was most frequently
      collected in the months of August (55.1%) in the Shannon traps, and in March 1999
      (19.2%), November 1999 (15.9%) and August 2000 (20.6%) in the Falcao traps. More
      phlebotomines were collected in Falcao traps installed in shelters for captive
      mammals (84.0%). CONCLUSION: There was a clear predominance of L. whitmani in the
      Ing Park. The greatest frequency of L. whitmani was in August from Shannon traps,
      and in March and November from Falcao traps. The peak activity of L. whitmani
      took place between 12:00 midnight and 2:00 a.m.

PMID- 14569344
TI  - [Scanning electron microscopy of eggs of Haemagogus leucocelaenus (Diptera:
      Culicidae)].
AB  - OBJECTIVE: To observe morphological details of the eggs of Haemagogus
      (Conopostegus) leucocelaenus, seen for the first time via scanning electron
      microscopy (SEM), with morphometric analysis of the main structures. METHODS:
      Eggs of Hg. leucocelaenus were obtained from females captured in the Biological
      Reserve of Tingua, State of Rio de Janeiro. Some of the eggs were kept for
      hatching and others underwent processing for scanning electron microscopy
      studies. Three eggs were submitted to morphometric analysis. The material was
      fixed in 2.5% glutaraldehyde and postfixed in 1% osmium tetroxide, both in 0.1M,
      pH 7.2 sodium cacodylate buffer, then dehydrated in ethanol and dried using the
      critical point method. This was then set up on metallic supports, covered with
      gold and observed using the Jeol 5310 scanning electron microscope. Measurements
      were made with the aid of the Semafore analysis software coupled to the electron
      microscope. RESULTS: The eggs presented elliptical outlines of approximately 574
      mm in length and 169 mm in width, with an egg index (l/w ratio) of 3.39 mm. The
      exochorion was extremely regular and had ornamentation that was usually hexagonal
      but sometimes pentagonal. Tubercles were observed on the chorionic cells,
      symmetrically arranged in relation to the longitudinal axis. Inside the cells,
      there were smaller, individualized tubercles, some arranged peripherally and
      others grouped to a greater or lesser extent in the center. The surface of the
      chorionic reticulum did not present rugosity. The micropylar apparatus was formed
      by a prominent continuous collar of 8.32 mm in thickness, with a slightly
      irregular surface. The micropylar disk was very evident, and was continuous with
      the collar. The micropyle was seen at the center of this disk, measuring 1.6 mm
      and with a micropylar apparatus of 27.3 mm in diameter. CONCLUSIONS: The
      ornamentation of the exochorion presents differences in relation to the tubercles
      of chorionic cells and the external chorionic reticulum between the eggs of Hg.
      Leucocelaenus, in comparison with the eggs of Hg. janthinomys and Hg. equinus,
      and also in relation to those of Aedes aegypti, Ae. albopictus and Ae.
      bahamensis. In various aspects, the eggs of Hg. leucocelaenus have more
      resemblance to those of Hg. Equinus than those of Hg. janthinomys, with greater
      differences presented in relation to the eggs of Hg. spegazzinii and Hg. lucifer.

PMID- 14569345
TI  - [Estimates from a complex survey].
AB  - OBJECTIVE: To evaluate the impact of sampling design and the effect of weighting
      on data from the 1996 Brazilian National Survey on Demography and Health.
      METHODS: Secondary data analysis was performed using a sample of 1,355
      interviewed women of the state of Sao Paulo. The sampling design of the National
      Survey of Household Sampling (PNAD) was used as a reference, and the municipality
      as primary sampling unit. The ratio estimator and Taylor's approximation for
      variance were calculated using the primary sampling units and several modalities
      of weighting. The indicators used to evaluate precision and validity were
      confidence intervals, design effects (Deff) and biases. RESULTS: For the four
      procedures, the differences between upper and lower point estimates for
      prevalence were not greater than 10%. The differences on ranges of confidence
      intervals were less than 20%. Use of condom and hormone injection were the
      variables that showed design effects greater than 1.5 and biases greater than
      0.20. CONCLUSIONS: According to the results, it could be said that the cluster
      sampling had an impact on the precision of the estimates for two out of six
      variables. The impact of weighting was not significant.

PMID- 14569346
TI  - [Updating of the distribution of Aedes albopictus in Brazil (1997-2002)].
AB  - Updating regarding the distribution of Aedes albopictus in Brazil is presented
      for the period from 1997 to 2002. Data from the yellow fever and dengue
      information system of the National Health Foundation is utilized. It can be seen
      that this species is present in 20 of the 27 Brazilian states.

PMID- 14569347
TI  - [Registration of the occurrence of Aedes albopictus in an urban zone in Manaus,
      Amazonas, Brazil].
AB  - Information is available regarding the presence of Aedes albopictus in several
      municipalities of the State of Amazonas. Specimens of this mosquito species have
      now, for the first time, been collected from an urban area of the municipality of
      Manaus, Amazonas, Brazil.

PMID- 14569348
TI  - [Household water reservoirs and control of Aedes aegypti].
AB  - Water reservoirs for domestic use are important sites for the development of
      Aedes aegypti. In poor areas, these reservoirs are often located outdoors upon
      flat rooftops. In modern architecture buildings, however, the same is seen even
      in high-class condominiums. Special attention should be given to these modern
      architectural constructions during entomological surveillance.

PMID- 14569349
TI  - [Male circumcision and HIV heterosexual transmission].
AB  - Since the early years of the AIDS epidemic significant geographic differences in
      HIV prevalence were reported within neighboring countries and neighboring regions
      within the same country in sub-Saharan Africa. These differences could not be
      fully explained by factors such as sexual behavior and condom use. Mounting
      epidemiological data have demonstrated that male circumcision is a major
      protective factor against male heterosexual HIV infection in sub-Saharan Africa
      and probably contributes to these significant differences in HIV prevalence. This
      is a review of African studies on the association between male circumcision and
      HIV infection, the origin of circumcision practices in human societies, potential
      prepuce mechanisms for increasing male vulnerability to heterosexual HIV
      infection, its association with other infectious and neoplastic diseases,
      controversies on the convenience of male circumcision as an HIV control strategy
      in Africa, the scarce Brazilian literature on male circumcision and perspectives
      of future research.

PMID- 14569350
TI  - Effect of dental adhesives on the exudative phase of the inflammatory process in
      subcutaneous tissue of rats.
AB  - The vascular changes in the subcutaneous connective tissue of rats induced by
      dentin bonding systems (one step) was studied and compared to those induced by
      saline solution (negative control) and Furacin (positive control), during the
      exudative phase of the inflammatory process. Twenty mg/kg of Evan's blue were
      injected intravenously in the vein of the rats' penises; 0.1 ml of each substance
      tested was inoculated in the subcutaneous tissue. After a 3 hour period the
      animals were sacrificed and their skins were excised and punched out with a
      standard steel 2.5 cm in diameter. The specimens were immediately immersed in 8
      ml of formamide and taken to a double boiler for 72 hours at 37 C, to remove the
      dye. The liquid containing the overflowed dye was filtered, analyzed in the
      spectrophotometer (620 nm) and classified according to the criteria established
      by Nagem-Filho, Pereira (1976). After statistical analysis, the irritative
      potential of the substances was ranked as follows: Furacin (severe) > Single Bond
      and Bond 1 (moderate - no significant differences between the dentin bonding
      systems tested) > saline solution (not significant as regards the irritation
      degree).

PMID- 14569351
TI  - Cytotoxic effects of cyanoacrylates used as retrograde filling materials: an in
      vitro analysis.
AB  - Cyanoacrylate has been used in medicine and dentistry for many years. It has been
      used as a postextraction dressing and retrograde filling material in endodontic
      surgery. The aim of this study was to evaluate the cytotoxic effects of
      Histoacryl and other two homologue ethyl cyanoacrylates, Super Bonder and
      Ultrabond, on cultured fibroblasts, using the Trypan blue dye exclusion assay.
      The cyanoacrylates were applied to round glass coverslips, which were placed in
      contact with NIH 3T3 cells. After 0, 6, 12 and 24 h (short-term assay; viability)
      and 1, 3, 5 and 7 days (long-term assay; survival), the cells were examined under
      phase light microscopy and counted. The data were compared by the Kruskal-Wallis
      test. In the short-term experiments, only the cultures of the Ultrabond group
      (GIV) presented significant smaller percentages of cell viability than the
      cultures of the other groups (GI: control; GII: Super Bonder; GIII: Histoacryl).
      Although the cultures of the Super Bonder group (GII) presented smaller
      percentages of cell viability than cultures of the other groups (GI, GIII, GIV)
      at the long-term assay, this group was the only experimental group presenting a
      continuous and progressive cell growth. Our results have shown an in vitro
      biocompatibility of Histoacryl and ethyl cyanoacrylate homologues. These
      cyanoacrylates could therefore be of importance for endodontic purposes.

PMID- 14569352
TI  - Analysis of the film thickness of a root canal sealer following three obturation
      techniques.
AB  - The aim of this study was to obtain a quantitative analysis of the film thickness
      of a root canal sealer formed after filling by three different techniques. Thirty
      human maxillary incisors were selected and access cavities were prepared using
      high-speed diamond stones and water spray. A size #15 K-Flexofile was introduced
      in the canal of each specimen until it was seen just at the apical foramen. The
      working length was determined to be 1 mm short of that position and the canals
      were prepared to an apical size of #45 K-Flexofile. Copious irrigation with 5.25%
      NaOCl (sodium hypochlorite) was used during and after instrumentation. The
      samples were divided into three groups and obturated as follows: G1 - lateral
      condensation, G2 - lateral condensation with an accessory cone, and G3 -
      continuous wave of condensation. The samples were evaluated in the cervical,
      middle and apical thirds. The film thickness of the root canal sealer was
      measured through a microscopic evaluation. Statistical analysis was obtained
      using the Wilcox test. Statistical analysis showed significant differences
      between G3 and G1, G3 and G2 (p < 0.05). In general, the lowest film thickness
      was observed in the continuous wave of condensation (G3). Lateral condensation
      with an accessory cone (G2) and lateral condensation (G1) demonstrated poorer
      results in this study, showing a higher film thickness. The small film thickness
      of the sealer obtained by the continuous wave of condensation technique may
      increase the clinical performance of this technique.

PMID- 14569353
TI  - Conduction velocity of the rabbit facial nerve: a noninvasive functional
      evaluation.
AB  - The aim of this study was to evaluate standardized conduction velocity data for
      uninjured facial nerve and facial nerve repaired with autologous graft nerves and
      synthetic materials. An evaluation was made measuring the preoperative
      differences in the facial nerve conduction velocities on either side, and
      ascertaining the existence of a positive correlation between facial nerve
      conduction velocity and the number of axons regenerated postoperatively. In 17
      rabbits, bilateral facial nerve motor action potentials were recorded pre- and
      postoperatively. The stimulation surface electrodes were placed on the auricular
      pavilion (facial nerve trunk) and the recording surface electrodes were placed on
      the quadratus labii inferior muscle. The facial nerves were isolated, transected
      and separated 10 mm apart. The gap between the two nerve ends was repaired with
      autologous nerve grafts and PTFE-e (polytetrafluoroethylene) or collagen tubes.
      The mean of maximal conduction velocity of the facial nerve was 41.10 m/s. After
      15 days no nerve conduction was evoked in the evaluated group. For the period of
      2 and 4 months the mean conduction velocity was approximately 50% of the normal
      value in the subgroups assessed. A significant correlation was observed between
      the conduction velocity and the number of regenerated axons. Noninvasive
      functional evaluation with surface electrodes can be useful for stimulating and
      recording muscle action potentials and for assessing the functional state of the
      facial nerve.

PMID- 14569354
TI  - Finite elements study of the Flexi Post and Flexi Flange post systems in a
      maxillary central incisor.
AB  - The use of post and core systems has become an excellent alternative for
      restoring endodontically treated teeth. The aim of this study was to evaluate the
      von Mises, maximal compressive and tensile stresses distribution using the Finite
      Element Method (FEM) on human teeth restored with different post and core
      systems. The analysis was made on endodontically treated maxillary central
      incisors. The post systems used in this investigation were the stainless steel or
      titanium Flexi Post/Flexi Flange. Composite resin was used as core material and
      resin cement was the cement material of choice to seat a full porcelain crown.
      The bi-dimensional mathematical model was created from pictures taken from an
      intact human maxillary central incisor and prefabricated posts. This image was
      transferred to a personal computer in the MSC/Nastran 4.5 software. A static and
      linear analysis treatment was performed when a 45  load of 100 N was applied on
      the lingual surface of the tooth. Based on the results obtained, it can be
      concluded that the post design and its material can alter the stress pattern
      distribution.

PMID- 14569355
TI  - Fluoride release by restorative materials before and after a topical application
      of fluoride gel.
AB  - The release of fluoride from restorative materials (Vitremer, Ketac-Fil, Fuji II
      LC and Freedom) was evaluated during two 15-day periods, before and after a
      topical application of acidulated phosphate fluoride gel (APF). For each
      material, 6 specimens were made, which were immersed in 2 ml of deionized water.
      The fluoride concentration dosages in the solutions were read at intervals of 24
      hours for 15 days. After this period, the specimens of each material received
      treatment with APF gel for 4 minutes and the fluoride released was analyzed at 24
      hour intervals during the following 15 days. The analysis of variance and the
      Tukey test (p < 0.05) showed that the total mean fluoride released during the
      initial 15 days was greater for Vitremer and Ketac-Fil and lower for Fuji II LC
      and Freedom; and in the final 15 days there was a difference in release readings,
      with the greatest value for Vitremer, followed by Fuji II LC, Ketac-Fil and
      Freedom. The comparison of the results between the 1st day and the 16th day
      (after gel application) showed a greater fluoride release on the 16th day for
      Vitremer, Fuji II LC and Freedom and was equal for Ketac-Fil. Although all the
      materials evaluated gained fluoride with the application of APF, the data suggest
      that the resin-modified ionomers are more efficient in releasing fluoride to the
      medium than the other materials.

PMID- 14569356
TI  - A 16S rDNA-based nested PCR protocol to detect Campylobacter gracilis in oral
      infections.
AB  - The aim of this study was to describe a 16S rDNA-based nested polymerase chain
      reaction (nPCR) assay to investigate the occurrence of Campylobacter gracilis in
      oral infections. Samples were collected from ten infected root canals, ten cases
      of acute periradicular abscesses and eight cases of adult marginal periodontitis.
      DNA extracted from the samples was initially amplified using universal 16S rDNA
      primers. A second round of amplification used the first PCR products to detect C.
      gracilis using oligonucleotide primers designed from species-specific 16S rDNA
      signature sequences. The nPCR assay used in this study showed a detection limit
      of 10 C. gracilis cells and no cross-reactivity was observed with nontarget
      bacteria. C. gracilis was detected in the three types of oral infections
      investigated - 4/10 infected root canals; 2/10 acute periradicular abscesses; and
      1/8 subgingival specimens from adult periodontitis. The method proposed in this
      study showed both high sensitivity and high specificity to directly detect C.
      gracilis in samples from root canal infections, abscesses, and subgingival
      plaque. Our findings confirmed that C. gracilis may be a member of the microbiota
      associated with distinct oral infections, and its specific role in such diseases
      requires further clarification.

PMID- 14569357
TI  - Evaluation of an oral preventive protocol in children with acute lymphoblastic
      leukemia.
AB  - This study was designed to assess the effectiveness of a preventive oral protocol
      in children receiving antineoplastic treatment for acute lymphoblastic leukemia
      (ALL) before initiating a larger intervention study. During a seven month period,
      fourteen children from two to ten years old with a diagnosis of ALL were
      evaluated. Patients with ALL who received a 0.12% chlorhexidine mouth rinse
      (seven children) were compared to a control group of patients who were not given
      the same preventive treatment (seven children) as to the occurrence of oral
      mucosal complications. Children in both groups received daily oral hygiene care,
      and were examined daily by the pediatric dentistry team until discharge. A
      significant decrease in the incidence of oral mucositis and ulceration was
      observed in the children who received a 0.12% chlorhexidine mouth rinse (p < 0.05
      by Fisher's exact test). The findings obtained in the present trial are
      encouraging, and suggest that the systematic application of a preventive protocol
      reduces the incidence of oral complications in children with ALL receiving
      chemotherapy.

PMID- 14569358
TI  - Candida spp. occurrence in oral cavities of breastfeeding infants and in their
      mothers' mouths and breasts.
AB  - This study aimed to determine the occurrence of Candida spp. in the oral cavity
      of predominantly breastfed infants and in their mothers' mouths and breasts, as
      well as in the oral cavity of bottlefed infants and in non-lactating women. One
      hundred and sixty nine women and eighty-five milk-fed infants took part in this
      study and were divided into four groups: 1) infants predominantly on
      breastfeeding (n = 55) and their mothers (n = 55); 2) infants on bottlefeeding (n
      = 30); 3) non-lactating women on whom oral collections were performed (n = 80)
      and, 4) non-lactating women on whom breast collections were performed (n = 34).
      Oral and mammary swabs were cultured on Sabouraud agar dextrose with
      chloramphenicol. The Candida yeast strains found were isolated and identified
      through morphological and biochemical tests. Candida species were much less
      frequent in infants who were predominantly breastfed than in those who were
      bottlefed. Yeasts were much more frequent on the breasts of lactating women, with
      statistical difference in relation to the control group.

PMID- 14569359
TI  - Evaluation of salivary flow in patients during head and neck radiotherapy.
AB  - Radiotherapy is frequently employed for the treatment of head and neck squamous
      cell carcinoma. Among the side effects, xerostomia is one of the most important.
      With the objective of evaluating the role of radiotherapy in salivary flow, we
      performed three salivary sample collections: at the beginning of, during, and
      immediately after radiotherapy. The results showed that the salivary flow values
      of the first collection were very similar to those of the control group. However,
      during treatment, there was a significant decrease of the salivary flow (p =
      0.0008), which continued low immediately after radiotherapy (p = 0.0009). Our
      study showed that radiotherapy leads to an important reduction of salivary flow
      during and after radiotherapy.

PMID- 14569360
TI  - Complex segregation analysis of 1,792 cleft lip and palate families in South
      America: 1967-1997.
AB  - Although several studies have demonstrated familial aggregation of nonsyndromic
      cleft lip with or without cleft palate (CL/P), its model of inheritance remains
      uncertain. We report the results of complex segregation analysis performed in
      South American families with a newborn affected with CL/P. Families of 1,792
      consecutive newborns affected with CL/P and registered during the period 1967 to
      1997 were studied. A model that did not include a major locus was the best
      fitting model for CL/P families. This result is in agreement with previous
      studies which showed a significant association of several putative susceptibility
      loci and CL/P, indicating that the genes involved in CL/P are likely to have only
      a very modest impact on disease risk.

PMID- 14569361
TI  - The impact of restorative treatment on tooth loss prevention.
AB  - A cross-sectional study was carried out to analyze tooth loss resulting from
      caries in relation to the number of times the extracted tooth had been restored,
      the type of caries diagnosed (primary or secondary), and socioeconomic indicators
      of patients from the city of Recife, Brazil. Ten public health centres and ten
      centres associated with health insurance companies were randomly selected. The
      size of the sample was calculated using a standard error of 2.5%. A confidence
      interval of 95% and a 50% prevalence of reasons for extractions were used for
      calculating the sample. The minimum size of the sample for meeting these
      requirements was 381 patients. Patients were randomly selected from the list of
      adults registered at each centre. A total of 410 patients were invited to take
      part in the study. The response rate was 100%, but 6 patients were excluded due
      to incompleteness of data in the questionnaire applied. An assessment was made to
      obtain the number of decayed, missing or filled teeth (DMFT index) and the
      reasons for extraction. The results showed a highly significant (p < 0.001)
      relationship between the number of times the tooth indicated for extraction had
      been restored and the reason for extraction being caries. Furthermore, the
      majority of teeth extracted due to caries had been restored two or more times. A
      highly statistically significant association was also observed between one
      indicator of use of dental services (F/DMFT) and extraction due to caries (p <
      0.001). The findings questioned the belief that tooth loss can be prevented in
      the general population by merely providing restorative treatment.

PMID- 14569362
TI  - Comparative study of the dental substrate used in shear bond strength tests.
AB  - The purpose of this study was to compare shear bond strength values obtained in
      human enamel and dentin with the values obtained in bovine teeth using two
      adhesive systems with different actions. Forty human tooth half-crowns and forty
      bovine tooth crowns were flattened to a minimum plain area of 5 mm in diameter.
      The samples were divided in four groups of 20 specimens each: 1) human enamel; 2)
      bovine enamel; 3) human dentin; 4) bovine dentin. The samples of each group were
      divided in 2 subgroups of 10 samples each, according to the adhesive system used:
      1) Scotchbond Multi-Purpose (SBMP); and 2) Clearfil Liner Bond 2V (CLB2V) applied
      according to the manufacturer's recommendations. Afterwards, restorations of Z100
      composite with cylindrical shape (4 mm diameter x 5 mm height) were made using a
      metallic mold to submit the samples to shear bond testing on an Instron universal
      testing machine, at a crosshead speed of 0.5 mm/min. The data were submitted to
      ANOVA and Tukey's test (5%). In enamel, there was no statistical difference
      between bovine and human teeth for SBMP (7.36 MPa, human; 8.24 MPa, bovine), nor
      for CLB2V (10.01 MPa, human; 7.95, bovine). In dentin, SBMP showed a
      statistically lower mean on human dentin (7.01 MPa) than on bovine dentin (11.74
      MPa). For CLB2V, there was no statistical difference between human (7.43 MPa) and
      bovine (9.27 MPa) substrates.

PMID- 14569363
TI  - Evaluation of the relation between the horizontal condylar angle and the internal
      derangement of the TMJ - a magnetic resonance imaging study.
AB  - This research aimed at assessing the relation between the horizontal condylar
      angle (HCA) and the internal derangement (ID) of the temporomandibular joint
      (TMJ), as a result of interference by the TMJ disk, in individuals undergoing
      magnetic resonance (MR) scans. The sample included a total of 144 TMJs (sagittal
      and coronal views) of 72 subjects, 15 of whom were male and 57 female, with ages
      ranging from 15 to 70. The scans were made in a Signa system (GE) model at a
      magnetic field magnitude of 1.5 T. Sixty-eight TMJs were found to be normal,
      while 46 showed anterior displacement with reduction. Of these, 41 had some kind
      of adaptive change in the condyle, while 5 showed degenerative changes. Anterior
      displacement without reduction was found in 29 joints, 12 of which showed
      adaptative changes in the condyle, while 17 showed degenerative changes. Only one
      posterior displacement of the articular disk was recorded. For the TMJs in which
      disk displacement was found, such values achieved 24.69  on the right side, and
      22.94  on the left side. Hence, it was possible for us to conclude that the HCA
      tends to increase in those TMJs where ID is present. For contralateral TMJs, a
      strong association was observed between HCA values (57.8%), state of normality
      (69.7%), and ID (66.7%). To corroborate such findings, a correlation between
      contralateral HCA values (63.31%) and the diagnosis for contralateral TMJs
      (68.05%) was determined. Thus, we could infer that there is a tendency between
      contralateral TMJs to share characteristics and conditions.

PMID- 14569364
TI  - Detection of highly and minimally leukotoxic Actinobacillus actinomycetemcomitans
      strains in patients with periodontal disease.
AB  - This study examined the prevalence of highly and minimally leukotoxic
      Actinobacillus actinomycetemcomitans in patients with periodontal disease. Pooled
      subgingival plaque samples from 136 patients with some form of periodontal
      disease were examined. Subjects were between 14 and 76 years of age. Clinical
      examinations included periodontal pocket depth (PD), plaque index (PI) and
      bleeding index (BI). The obtained plaque samples were examined for the presence
      of highly or minimally leukotoxic A. actinomycetemcomitans strains by the
      polymerase chain reaction (PCR). Chi-square and logistic regression were
      performed to evaluate the results. Forty-seven subjects were diagnosed with
      gingivitis, 70 with chronic periodontitis and 19 with aggressive periodontitis.
      According to chi-square there was no significant correlation detected between PD
      (chi2 = 0.73), PI (chi2 = 0.35), BI (chi2 = 0.09) and the presence of the highly
      leukotoxic A. actinomycetemcomitans. The highly leukotoxic A.
      actinomycetemcomitans strains were correlated with subjects that were 28 years of
      age and younger (chi2 = 7.41). There was a significant correlation between highly
      leukotoxic A. actinomycetemcomitans and aggressive periodontitis (chi2 = 22.06).
      This study of a Brazilian cohort confirms the strong association between highly
      leukotoxic A. actinomycetemcomitans strains and the presence of aggressive
      periodontitis.

PMID- 14569365
TI  - Development and control of caries lesions on the occlusal surface using a new in
      vivo caries model.
AB  - The aim of this study was to develop a new in vivo caries model for the occlusal
      surface and to describe the enamel features observed before and after dental
      plaque control (DPC). Four volunteers (12-15 years old) participated in the
      experiment, each of which was due to have 2 homologous first premolars extracted
      for orthodontic reasons. Test surfaces did not present visible signs of
      demineralization, opacities or fillings. A wire mesh was used to promote dental
      plaque accumulation on the occlusal surface. After 4 weeks, the wire mesh was
      removed and DPC was performed. In Groups 1 and 2, DPC was performed by the
      subjects daily and, in Groups 3 and 4, DPC was performed by the subjects daily
      and by the professional weekly. One tooth/pair of Groups 1 and 3 was extracted
      after 2 weeks. One tooth/pair of Groups 2 and 4 was extracted after 4 weeks. All
      test surfaces showed demineralization after the wire mesh was removed. The
      observed re-establishment of the enamel brightness was directly related to the
      increase of the DPC duration. In polarized light microscopy, interindividual
      differences varying from pseudoisotropic areas to enamel lesions were noted in
      specimens submitted to 2 weeks of DPC. Specimens submitted to 4 weeks of DPC
      showed less tissue porosity. It was concluded that the new in vivo caries model
      was effective since all occlusal surfaces presented clinical and microscopic
      signs of mineral loss in different stages after 4 weeks of cariogenic challenge.
      After DPC on the test surfaces, there was a reduction of mineral loss suggesting
      control of demineralization on these surfaces.

PMID- 14569366
TI  - [Coronary artery disease in the very elderly. Aggressive or conservative
      approach?].

PMID- 14569367
TI  - Behavior of cardiac variables in animals exposed to cigarette smoke.
AB  - OBJECTIVE: To assess the behavior of cardiac variables in animals exposed to
      cigarette smoke. METHODS: Two groups of Wistar rats were studied as follows:
      control group (C), comprising 28 animals; and smoking group (S), comprising 23
      animals exposed to cigarette smoke for 30 days. Left ventricular cardiac function
      was assessed in vivo with transthoracic echocardiography, and myocardial
      performance was analyzed in vitro in preparations of isolated left ventricular
      papillary muscle. The cardiac muscle was assessed in isometric contractions with
      an extracellular calcium concentration of 2.5 mmol/L. RESULTS: No statistical
      difference was observed in the values of the body variables of the rats and in
      the mechanical data obtained from the papillary muscle between the control and
      smoking groups. The values of left ventricular systolic diameter were
      significantly greater in the smoking animals than in the control animals (C=3.39
      +/- 0.4 mm and S=3.71 +/- 0.51 mm, P=0.02). A significant reduction was observed
      in systolic shortening fraction (C=56.7 +/- 4.2% and S=53.5 +/- 5.3%, P=0.02) and
      in ejection fraction (C=0.92 +/- 0.02 and S=0.89 +/- 0.04, P=0.01). CONCLUSION:
      The rats exposed to cigarette smoke had a reduction in left ventricular systolic
      function, although their myocardial function was preserved.

PMID- 14569368
TI  - Coronary heart disease clinical manifestation and risk factors in Japanese
      immigrants and their descendents in the city of Sao Paulo.
AB  - OBJECTIVE: To assess whether a difference exists in coronary heart disease
      clinical manifestations and the prevalence of risk factors between Japanese
      immigrants and their descendents in the city of Sao Paulo. METHODS: Retrospective
      analysis of coronary artery disease clinical manifestations and the prevalence of
      risk factors, comparing 128 Japanese immigrants (Japanese group) with 304
      Japanese descendents (Nisei group). RESULTS: The initial manifestation of the
      disease was earlier in the Nisei group (mean=53 years), a difference of 12 years
      when compared with that in the Japanese group (mean=65 years) (P<0.001).
      Myocardial infarction was the first manifestation in both groups (P=0.83). The
      following parameters were independently associated with early coronary events:
      smoking (OR=2.25; 95% CI=1.35-3.77; P<0.002); Nisei group (OR=10.22; 95% CI=5.64
      18.5; P<0.001); and female sex (OR=5.04; 95% CI=2.66-9.52; P<0.001). CONCLUSION:
      The clinical presentation of coronary heart disease in the Japanese and their
      descendents in the city of Sao Paulo was similar, but coronary heart disease
      onset occurred approximately 12 years earlier in the Nisei group than in the
      Japanese group.

PMID- 14569369
TI  - ProBNP for stratifying patients with heart failure.
AB  - OBJECTIVE: To verify whether the serum levels of N-Terminal ProBNP fraction
      (ProBNP) allow us to identify with accuracy the clinical functional status of
      patients with heart failure (HF), because the clinical diagnosis of this syndrome
      is based basically on clinical data when the complementary tests have lower
      specificity. METHODS: Sixty-nine patients with a history of HF were studied.
      Their mean age of was 53.5 years and 78.3% were males. All underwent clinical and
      echocardiographic evaluations and a test to determine the serum dosage of ProBNP.
      According to clinical manifestation, patients were in the following functional
      classes (FC), 14% FC I, 40.6% FC II, 28.1% FC III, and 23.4% FC IV. The mean
      ejection fraction (EF) was 0.28. RESULTS: ProBNP did not differ according to age,
      sex, and cause of cardiopathy. No correlation existed between EF and the ProBNP
      serum level. ProBNP levels were significantly lower in patients in FC I than
      those in FC II (42 vs 326.7 pmol/L; P=0.0001), and in FC II than those in FC III
      (P=0.01). ProBNP levels did not differ statically between FC III and IV patients
      (888.1 vs 1082.8 pmol/L; P=0.25). ProBNP values greater than 100 pmol/L identify
      patients with decompensated HF with a sensitivity of 98%. CONCLUSION: ProBNP
      values over 100 pmol/L were indicative of HF, and patients with advanced HF had
      values over 270 pmol/L. A ProBNP dosage test was an excellent auxiliary in the
      clinical characterization of patients with HF.

PMID- 14569370
TI  - Prevalence of dyslipidemia and risk factors in Campos dos Goytacazes, in the
      Brazilian state of Rio de Janeiro.
AB  - OBJECTIVE: To determine the prevalence of dyslipidemias in adults in the city of
      Campos dos Goytacazes, in the Brazilian state of Rio de Janeiro, and to identify
      its relation to risk factors. METHODS: Cross-sectional, population-based,
      observational study with sampling through conglomerates and stratified according
      to socioeconomic levels, sex, and age, with 1,039 individuals. Risk factors,
      familial history, blood pressure, anthropometric measurements, glucose,
      triglycerides and cholesterol were determined. RESULTS: The following prevalences
      were observed: of dyslipidemias 24.2%; of hypercholesterolemia, 4.2%; of elevated
      LDL-C, 3.5%; of low HDL-C, 18.3%; and of hypertriglyceridemia, 17.1%. The
      following mean levels were observed: cholesterol, 187.6 +/- 33.7 mg/dL; LDL-C,
      108.7 +/- 26.8 mg/dL; HDL-C, 48.5 +/- 7.7 mg/dL; and triglycerides, 150.1 +/-
      109.8 mg/dL. The following variables showed a positive correlation with
      dyslipidemia: increased age (P<0.001), male sex (P<0.001), low familial income
      (P<0.001), familial history (P<0.01), overweight/obesity (P<0.001), waist measure
      (P<0.001), high blood pressure (P<0.001), and diabetes mellitus (P<0.001). The
      following variables had no influence on dyslipidemias: ethnicity, educational
      level, smoking habits, and sedentary lifestyle. CONCLUSION: The frequency of
      lipid changes in the population studied was high, suggesting that measures for
      the early diagnosis should be taken, in association with implementation of
      programs for primary and secondary prevention of atherosclerosis.

PMID- 14569371
TI  - Aneurysmal dilation of the reimplant segment of the visceral vessels after
      thoracoabdominal aneurysm correction.
AB  - We present a case of aneurysmal dilation of the aortic residual segment,
      involving abdominal vessels in corrective surgeries for thoracoabdominal aortic
      aneurysm, through the identification of risk groups for recurrent dilation,
      aiming at using a specific operative technique with a branched graft, to prevent
      aneurysm relapse.

PMID- 14569372
TI  - Behavior of inflammatory markers of myocardial injury in cardiac surgery:
      laboratory correlation with the clinical picture of postpericardiotomy syndrome.
AB  - OBJECTIVE: To verify the association of serum markers of myocardial injury, such
      as troponin I, creatinine kinase, and creatinine kinase isoenzyme MB, and
      inflammatory markers, such as tumor necrosis factor alpha (TNF-alpha), C-reactive
      protein, and the erythrocyte sedimentation rate in the perioperative period of
      cardiac surgery, with the occurrence of possible postpericardiotomy syndrome.
      METHODS: This was a cohort study with 96 patients undergoing cardiac surgery
      assessed at the following 4 different time periods: the day before surgery (D0);
      the 3rd postoperative day (D3); between the 7th and 10th postoperative days (D7
      10); and the 30th postoperative day (D30). During each period, we evaluated
      demographic variables (sex and age), surgical variables (type and duration,
      extracorporeal circulation), and serum dosages of the markers of myocardial
      injury and inflammatory response. RESULTS: Of all patients, 12 (12.5%) met the
      clinical criteria for a diagnosis of postpericardiotomy syndrome, and their mean
      age was 10.3 years lower than the age of the others (P=0.02). The results of the
      serum markers for tissue injury and inflammatory response were not significantly
      different between the 2 assessed groups. No significant difference existed
      regarding either surgery duration or extracorporeal circulation. CONCLUSION: The
      patients who met the clinical criteria for postpericardiotomy syndrome were
      significantly younger than the others were. Serum markers for tissue injury and
      inflammatory response were not different in the clinically affected group, and
      did not correlate with the different types and duration of surgery or with
      extracorporeal circulation.

PMID- 14569373
TI  - Assessment of cardiovascular risk factors in a rural community in the Brazilian
      state of Bahia.
AB  - OBJECTIVE: To assess the frequency of cardiovascular risk factors in the rural
      community of Cavunge, in the Brazilian state of Bahia. METHODS: A cross-sectional
      study was carried out with 160 individuals (age>19 years) randomly drawn from
      those listed in the population census of the Cavunge Project. The following
      parameters were studied: arterial hypertension, dyslipidemia, diabetes, obesity,
      smoking, waist-hip ratio (WHR), physical activity, and overall cardiovascular
      risk classified according to the Framingham score. The assessing parameters used
      were those established by the III Brazilian Consensus on Hypertension and the II
      Brazilian Consensus on Dyslipidemia. RESULTS: Of the randomly drawn individuals,
      126 with a mean age of 46.6 +/- 19.7 years were included in the study, 43.7% of
      whom were males. The frequency of arterial hypertension was 36.5%; 20.4% of the
      individuals had cholesterol levels > or =240 mg/dL; 31.1% of the individuals had
      LDL-C levels >130 mg/dL; 4% were diabetic; and 39.7% had a high-risk Framingham
      score. Abdominal obesity was observed in 41.3% of the population and in 57.7% of
      the females. High caloric-expenditure (HCE) physical activities were performed by
      56.5% of the individuals. The HCE group had a greater frequency of normal
      triglyceride levels (63% vs 44%; P=0.05), no diabetes, and WHR tending towards
      normal (46% vs 27%, P=0.08) as compared with those in the low caloric-expenditure
      group. CONCLUSION: Cardiovascular risk factors, such as hypertension and
      hypercholesterolemia, are frequently found in rural communities. The greatest
      frequency of normal triglyceride levels and normal WHR in the HCE group
      reinforces the association between greater caloric expenditure and a better risk
      profile.

PMID- 14569374
TI  - Demographic characteristics of the population undergoing cine coronary
      angiography at the Instituto do Coracao of the Medical School of USP from 1986 to
      1995.
AB  - OBJECTIVE: To obtain information about the profile and behavior of a population
      with ischemic heart disease undergoing cine coronary angiography and to determine
      disease severity. METHODS: Retrospective study assessing patients hospitalized at
      InCor from 1986 to 1995, in which the variables age, sex, and number of major
      coronary arteries with obstruction degree > or =40% were analyzed. RESULTS: We
      studied 18,221 patients and observed a significant increase in the number of
      females (22.8% to 25.2%, P=0.001) and an increase in age (57.1 +/- 29.3 to 60.4
      +/- 10.7 years, P=0.0001). A significant increase in the incidence of multivessel
      disease was observed, which was more frequent among males (69.2% and 64.5%) and
      among the older patients (59.8 +/- 9.8 and 56.8 +/- 10.7 years, P=0.0001). A
      reduction in the incidence of single-vessel disease was also observed (66.2% vs
      69.2% and 33.8% vs 30.5%, respectively, P<0.0001). CONCLUSION: A change in the
      profile of the population studied was observed as follows: patients undergoing
      cine coronary angiography at InCor were older, had a greater number of impaired
      major coronary arteries, and the number of females affected increased, leading to
      indices suggestive of a poorer prognosis.

PMID- 14569375
TI  - Ligation of the thoracic duct for the treatment of chylothorax in heart diseases.
AB  - In children, chylothorax occurs mainly after cardiac and thoracic surgeries. One
      of the recommended postsurgery treatments is ligation of the thoracic tract, when
      all other conservative treatments have failed. We report 4 cases of chylothorax
      in patients who were successfully treated with this approach, which resulted in a
      decrease in pleural drainage without recurrent chylothorax.

PMID- 14569376
TI  - [Clinicoradiological correlation - case 9/2003 - Instituto do Coracao do Hospital
      das Clinicas - FMUSP].

PMID- 14569379
TI  - [Diagnosis of erectile dysfunction--what is still needed today?].
AB  - Diagnostic procedures for erectile dysfunction (ED) are still mandatory because
      ED can be the presenting symptom for a variety of diseases such as diabetes
      mellitus, coronary artery disease, atherosclerosis, hypertension and
      hyperlipidemia. Invasive testing for ED has decreased due to the high responder
      rate for oral PDE-5 inhibitors.

PMID- 14569377
TI  - [Ultrasound myocardial tissue characterization].

PMID- 14569380
TI  - [Drug therapy of erectile dysfunction--the current status].
AB  - In the medicinal therapy of erectile dysfunction (ED), both oral as well as local
      application are possible. The introduction of the PDE-5 inhibitor Sildenafil, as
      the first highly potent oral therapy for ED, caused dramatic changes in the
      diagnostic and therapeutic strategies in this area. The later PDE-5 inhibitors
      Tadalafil and Vardenafil show, as far as it is currently possible to judge, a
      similar profile to Sildenafil. The only previously available oral therapeutic,
      Yohimbin, plays an insignificant role, and the initial hopes for Apomorphin as an
      ED therapeutic have settled to a realistic level. Local application therapies
      have also become less important, with the intra-urethral application of PGE(1)
      being reduced to a few clinical indicated situations. The intra-cavernosal
      pharmacotherapy with PGE(1) is considered the gold standard when oral therapies
      do not work or can not be used.

PMID- 14569381
TI  - [Therapy of erectile dysfunction in 2005].
AB  - Erectile dysfunction (ED) management in the following 3-5 years will be dominated
      by substances targeting the L-arginine-NO-guanylate cyclase-cGMP-PDE-5 pathway,
      resulting in an intracellular elevation of the cGMP concentrations. Promising
      alternatives to the PDE-5 inhibitors, such as guanylate cyclase activators and
      Rho-kinase inhibitors, may also effectively compliment a PDE-5 inhibitor.
      Intranasal application of the melanocortin agonist PT 141 (Melanotan II) seems to
      be promising. As scheduled sexual activities are not preferred by the majority of
      couples, the future of ED-therapy will focus on drugs with a 1-2 day long
      efficacy window, or a daily bedtime application of low dosage agents which result
      in nocturnal reoxygenation of the cavernous bodies and in turn in functional
      improvement. Elevation of the cGMP levels and improvement of endothelial function
      as a result of this approach also promises benefits in cardiovascular diseases
      and in LUTS.

PMID- 14569382
TI  - [Surgical therapy of erectile dysfunction. Current status].
AB  - In the light of the current domination of oral pharmacotherapy for the treatment
      of erectile dysfunction, the aim of this paper is to give a critical and up-to
      date overview of the possibilities of surgical therapy. We evaluate possible
      therapy options such as penile vein surgery, arterial revascularisation surgery
      and penile prosthetics surgery. Today, vein surgery has faded into total
      insignificance due to the efficiency of oral and intracavernous therapeutics, and
      as a result of the pathomechanism of cavernoveinous insufficiency and the
      disappointing long-term results published in the literature. A similar fate has
      been met by penile revascularisation surgery, which today is performed only in a
      very limited number patients with strict selection criteria such as age and
      exclusion of diabetes mellitus. Thus, aside from pharmacotherapy, penile
      prosthetics is the only surgical therapy option maintaining its significance as a
      cure for erectile dysfunction. There are convincing long-term results with a high
      degree of patient and partner satisfaction, high patient acceptance and a good
      functional durability of the mostly three-part hydraulic implants.

PMID- 14569383
TI  - [Erectile dysfunction--value of neurophysiologic diagnostic procedures].
AB  - Neurogenic, particularly autonomic disorders, frequently contribute to the
      etiology and pathophysiology of erectile dysfunction. Parasympathetic and
      sympathetic outflow mediates erection. Noncholinergic, nonadrenergic
      neurotransmitters induce activation of cyclic monophosphates, leading to
      relaxation of smooth muscles of the corpora cavernosa and by this to tumescence
      and rigidity, i.e. erection. The diagnosis of neurologic causes of erectile
      dysfunction requires a detailed history and neurologic examination. Conventional
      neurophysiological procedures evaluate the function of rapidly conducting,
      thickly myelinated nerve fibers only. Therefore, techniques such as sphincter ani
      externus electromyography, latency measurements of the pudendal nerve or
      bulbocavernosus reflex studies frequently do not contribute to the diagnostic
      process. The evaluation of small nerve fibers that are essential for erection,
      for example by means of psychophysical quantitative thermotesting, might improve
      the diagnosis of neurogenic causes of erectile dysfunction. In addition, the
      assessment of heart rate variability at rest, during metronomic breathing,
      Valsalva maneuver, and active standing might be helpful to identify an autonomic
      neuropathy as the cause of erectile dysfunction.

PMID- 14569384
TI  - [Prostate carcinoma and erectile dysfunction. Which therapy when?].
AB  - The quality of life of patients after radical prostatectomy is mainly influenced
      by erectile dysfunction (ED) and incontinence. New criteria for treatment and
      patient selection give us the opportunity to restore sexual function in more
      patients. When ED is present, we should not wait for 24 months for natural
      restitution. PDE-5-inhibitors, intracavernosal self injection therapy and the
      vacuum constriction device are effective and conform to both patient and economic
      preference.Therefore, every urologists should be able to offer his patients an
      individual and successful approach to the therapy of ED after prostate cancer.

PMID- 14569385
TI  - [Sacral neuromodulation in treatment of functional disorders of the lower urinary
      tract. An overview of basic principles, indications, outcomes].
AB  - Over the last few years, sacral neuromodulation has become an established
      treatment option for dysfunctions of the lower urinary tract. It fills the gap
      that used to exist between conservative therapy and costly invasive methods such
      as urinary drainage via a deactivated bowel segment. Initially, the clinical
      value of sacral neuromodulation was controversial even among neurourologists.
      This was mainly due to a lack of understanding of the physiological processes,
      uncertain diagnostics, the design of the hardware, and a surgical topography
      relatively unknown to the urologist. In the meantime, however, sacral
      neuromodulation has become a standard part of clinical routine with respect to
      the treatment of dysfunctions of the lower urinary tract, and it is regularly
      employed in various urological institutions across Europe and the USA. This form
      of treatment, which is the final straw for patients who believed themselves-after
      many frustrated therapy attempts-to be "hopeless cases," can now also
      successfully be employed as an ambulatory measure. The latest data from our
      hospital, as well as contributions presented at the last DGU Congress in
      Wiesbaden, indicate that patients with neurogenic urinary retention are the most
      likely to profit from this treatment option.

PMID- 14569387
TI  - [Superior vena cava syndrome with bilateral jugular and subclavian vein
      thrombosis. Paraneoplastic manifestion of renal cell carcinoma].
AB  - At present thrombosis of the superior vena cava is an uncommon event that is now
      more frequently associated with diagnostic or therapeutic catheterization. If an
      apparent spontaneous thrombosis occurs, malignancy should be considered in the
      differential diagnosis. One case of clinically symptomatic thrombosis of the
      internal jugular, subclavian, and superior vena cava is presented. We detected an
      asymptomatic left renal cell carcinoma in a 54-year-old patient and nephrectomy
      was performed. Increased blood coagulability as part of a paraneoplastic syndrome
      was considered to be the possible etiology. In patients with otherwise
      unexplained superior vena cava thrombosis, examination not only of the head and
      neck but also of the abdomen, retroperitoneum, and pelvis should be pursued. A
      review of the literature pertinent to this rare case is provided.

PMID- 14569388
TI  - [8th symposium of the Greek-German Society of Urology e.V. 3-6 July 2003 Rhodes,
      Greece].

PMID- 14569386
TI  - [Reducing the risk of superficial bladder cancer recurrence with 5-aminolevulinic
      acid-induced fluorescence diagnosis. Results of a 5-year study].
AB  - A prospective monocentre randomized parallel-group Phase III trial was performed
      to investigate whether primary transurethral resection (TUR) with 5
      aminolevulinic acid induced Fluorescence diagnosis (FD) allows for a more
      thorough TUR of superficial Bladder Carcinoma compared to conventional white
      light (WL). Evaluation of residual tumor rate and recurrence free survival were
      defined as the two primary study endpoints. The residual tumor rate was 25.2% in
      the WL arm (n=103) vs. 4.5% in the (n=88) FD arm (p<0.0001). Median follow up of
      the patients in the WL arm was 42 months (range 25-61) compared to 43 (range 24
      61) in the FD arm. Recurrence free survival in the fluorescence diagnosis group
      was 90.9%, 90.9% und 85 % after 12, 24 and 48 months compared with 78.6%, 69.9%
      und 60.7 %, respectively, in the white light group (p=0.0005). This superiority
      proved to be independent of risk group. The adjusted hazard ratio of fluorescence
      diagnosis versus white light transurethral resection was 0.29 (95% CI: [0.15;
      0.56]). ALA induced FD is statistically significantly superior to conventional WL
      TUR with respect to both residual tumor rate and recurrence-free survival. The
      differences in RFS imply that FD offers a clinically relevant procedure to reduce
      the number of tumor recurrences.

PMID- 14569389
TI  - Intravascular palpography for high-risk vulnerable plaque assessment.
AB  - BACKGROUND: The composition of an atherosclerotic plaque is considered more
      important than the degree of stenosis. An unstable lesion may rupture and cause
      an acute thrombotic reaction. Most of these lesions contain a large lipid pool
      covered by an inflamed thin fibrous cap. The stress in the cap increases with
      decreasing cap thickness and increasing macrophage infiltration. Intravascular
      ultrasound (IVUS) palpography might be an ideal technique to assess the
      mechanical properties of high-risk plaques. TECHNIQUE: Palpography assesses the
      local mechanical properties of tissue using its deformation caused by the
      intraluminal pressure. IN VITRO VALIDATION: The technique was validated in vitro
      using diseased human coronary and femoral arteries. Especially between fibrous
      and fatty tissue, a highly significant difference in strain (p = 0.0012) was
      found. Additionally, the predictive value to identify the vulnerable plaque was
      investigated. A high-strain region at the lumen-vessel wall boundary has an 88%
      sensitivity and 89% specificity for identifying such plaques. IN VIVO VALIDATION:
      In vivo, the technique was validated in an atherosclerotic Yucatan minipig animal
      model. This study also revealed higher strain values in fatty than fibrous
      plaques (p < 0.001). The presence of a high-strain region at the lumenplaque
      interface has a high predictive value to identify macrophages. PATIENT STUDIES:
      Patient studies revealed high-strain values (1-2%) in thin-cap fibrous atheroma.
      Calcified material showed low strain values (0-0.2%). With the development of
      three-dimensional (3-D) palpography, identification of highstrain spots over the
      full length of a coronary artery becomes available. CONCLUSION: Intravascular
      palpography is a unique tool to assess lesion composition and vulnerability. The
      development of 3-D palpography provides a technique that may develop into a
      clinical tool to identify the high-risk plaque.

PMID- 14569391
TI  - Plaque characterization and atherosclerosis evaluation by coronary angioscopy.
AB  - When observed by angioscopy, the culprit lesions of acute coronary syndrome (ACS)
      have a common appearance of a yellow plaque with irregular surface covered by a
      thrombus. Angioscopy is a powerful device to detect not only the ruptured plaques
      at ACS lesions but also the yellow plaques in their early stages. The culprit
      lesions of ACS are sometimes detected by angioscopy even in the angiographically
      normal segments of coronary arteries. Angioscopy can further classify the culprit
      lesions of ACS as (1) vasospasm, (2) plaque rupture, or (3) plaque erosion
      according to the angioscopic definitions. These classifications may be beneficial
      to determine the treatment strategy. Anti-vasospastic medications rather than
      stenting may be more suitable for the treatment of vasospasm-induced ACS.
      Percutaneous coronary intervention (PCI) of ruptured plaque rather than of
      erosive plaque tends to cause more distal embolization with thrombus and plaque
      contents. Therefore, distal protection device may be more beneficial for those
      cases. Although angioscopy may be able to identify vulnerable plaques as the
      plaques of intensive yellow color, it may be more practical to identify the
      patients at high risk of suffering ACS by evaluating the extent of coronary
      atherosclerosis. The process and the time course of plaque formation, maturation,
      and disruption are left to be clarified, however, the number of yellow plaques or
      the yellow color intensity of those plaques may be a marker of coronary
      atherosclerosis. Angioscopy should be useful not only as a diagnostic tool but
      also as an investigational tool. The effect of medications that regress coronary
      atherosclerosis may be evaluated by the angioscopically determined markers of
      coronary atherosclerosis.

PMID- 14569390
TI  - Optical Coherence Tomography (OCT). Potential of a new high-resolution
      intracoronary imaging technique.
AB  - BACKGROUND: It is believed that most myocardial infarctions result from the
      rupture of "vulnerable plaques", that share certain common characteristics. These
      plaques typically consist of a lipid-rich core in the central portion of the
      thickened intima, covered by a thin friable fibrous cap. Today, one of the
      important challenges in the field of interventional cardiology is how to identify
      minor or silent plaques that carry the risk of thrombosis resulting in severe
      cardiac events. Current imaging technologies lack the resolution to reliably
      identify these lesions. OCT: Optical Coherence Tomography (OCT) might have the
      potential to fill this role. OCT is a new non-contact, light-based imaging
      modality providing in situ images of tissues at near histologic resolution. As
      shown in various preclinical and clinical reports, OCT allows the identification
      of mural as well as luminal morphologies including lumen dimensions, plaques,
      thrombi, dissections, tissue flaps as well as information on stent geometries
      including apposition and symmetry. Trials comparing intravascular ultrasound
      (IVUS) and OCT demonstrated that OCT provided additional morphologic information,
      which could be used to improve plaque characterization. CONCLUSION: OCT has the
      potential to provide a new and more detailed look into the vessel wall, which
      might help to identify plaques that are at risk of rupture, and furthermore,
      which will influence and guide the appropriate patient-specific therapeutic
      approach.

PMID- 14569392
TI  - Intracoronary thermography.
AB  - Arteriosclerosis is an inflammatory disease. Inflammatory processes play a role
      in the initiation of plaque development and the early stages of the disease as
      well as in complex plaques and complications such as intraarterial thrombosis. A
      method to detect inflammation in coronary arteries has the potential to
      characterize both local and systemic activation of arteriosclerotic plaque
      disease. It could help to define in more detail what constitutes a vulnerable
      plaque or vulnerable vessel and thus improve the prediction of acute coronary
      syndromes. Intracoronary thermography records a cardinal sign of inflammation.
      Heat is probably produced by (activated) macrophages. Experimental work has
      suggested that thermal heterogeneity is present in arteriosclerotic plaques and
      that increased temperature is found at the site of inflammatory cellular
      macrophage-infiltration. Preliminary experience in patients undergoing coronary
      angiography has demonstrated that it is safe and feasible to perform
      intracoronary thermography using various systems. A graded relationship between
      thermal heterogeneity and clinical symptoms has been reported, with the greatest
      temperature elevation in acute myocardial infarction. Increases in thermal
      heterogeneity appeared to be associated with a comparably unfavorable long-term
      prognosis. Intracoronary thermography has the potential to provide insights into
      location and extent of inflammation as well as the prognostic consequences.
      Currently, this novel method and the underlying concepts are extensively
      evaluated.

PMID- 14569393
TI  - [Noninvasive plaque imaging using contrast-enhanced cardiac computed tomography].
AB  - Recent technical advances in both multislice spiral computed tomography (MSCT)
      and electron-beam computed tomography (EBT) renewed the clinicians' interest in
      the potentials of CT-based, contrast-enhanced, noninvasive coronary angiography.
      Despite the fact that invasive, selective coronary angiography remains the "gold
      standard", cardiac CT lumenography permits visualization of flow-limiting
      coronary stenosis with a sensitivity and specificity of about 90%. The method is,
      nevertheless, limited by imaging artifacts which are due to extensive coronary
      calcifications, or, especially in the right coronary and circumflex artery, to
      rapid coronary motion. Moreover, the clinical value for the exclusion of
      obstructive coronary artery disease is not yet established, and further
      prospective studies are required. On the other hand, cardiac CT permits reliable
      estimation of coronary calcification and quantification of overall coronary
      plaque burden and thereby allows risk assessment to predict the individual
      cardiovascular risk. Diagnostic accuracy may be enhanced by combining assessment
      of calcified plaque burden and contrast imaging. The newer MSCT technology also
      allows for differentiation of coronary lesion configuration, especially of
      noncalcified plaques. However, very few data are currently available on this
      aspect, and the future clinical relevance of this promising technique remains to
      be proven. The purpose of this article is to describe the principles and
      potentials of contrast-enhanced coronary CT imaging and to summarize the
      practical limitations with the currently available scanning equipment.

PMID- 14569394
TI  - [Fibrinogen and atherothrombosis: vulnerable plaque or vulnerable patient?].
AB  - Fibrinogen is far more important as a risk factor for acute cardiovascular
      syndromes than generally recognized. Evidence from a recent metaanalysis
      (including 22 studies of 63,736 subjects and 5,717 events [1] suggests that the
      risk for myocardial infarction and stroke almost doubles if the fibrinogen level
      exceeds 3.03 g/l (measured according to Clauss) with an odds ratio of 1.99 and a
      95% confidence interval of 1.85-2.13. The predictive value of fibrinogen levels
      equally applies to men and women, young and old, primary and secondary
      prevention. Repeated fibrinogen measurements are particularly helpful with
      emphasis on high risk patients: concentrations of the upper tertile indicate a
      92% higher risk of impending acute cardiovascular syndromes, as evidenced by a
      metaanalysis evaluating five prospective studies with 9,639 participants and 671
      events [1]. Together with other risk factors such as hypertension,
      hypercholesterolemia, or diabetes, the risk of fatal and nonfatal acute
      cardiovascular syndromes may further increase by 6-12- fold, while fibrinogen
      remains an independent risk factor for both cardiac and extracardiac
      atherothrombotic complications, as well as for iatrogenic complications like
      restenosis following PTCA or stenting. Fibrin(ogen) and his effector thrombin
      substantially determine the extent and outcome of atherothrombotic complications,
      because they are the molecules linking the mutually dependent events of
      atherogenesis, coagulation/fibrinolysis, rheology/vasotonus, and inflammation.
      Interventional studies on fibrinolytic and defibrinating substances, as well as
      GpIIb/IIIa-inhibitors for treatment of acute cardiovascular syndromes have
      confirmed the benefit of fibrinogen reduction and extended the experimental
      evidence for the relevance of fibrin(ogen) in the pathogenesis of these
      syndromes. Accordingly, the preventive use of fibrates leading to moderate
      reductions in plasma cholesterol and fibrinogen diminished significantly the rate
      of reinfarction. The emerging possibilities from a more than 50% fibrinogen
      reduction (by studies using H.E.L.P. apheresis) strengthened the therapeutic
      concept to free the blood from all risk factors-as effective as it can be-in
      order to achieve an optimal plaque regression, since changes in the blood
      composition strongly affect the fragility and stability of the atherosclerotic
      plaques.

PMID- 14569395
TI  - Type 2 diabetes mellitus is rare but not absent in children under 15 years of age
      in Austria.
AB  - Until recently, most children with diabetes mellitus had type 1 diabetes (T1DM).
      The prevalence of type 2 diabetes (T2DM) is on the rise in North America,
      especially in risk populations such as the American Indians. Few epidemiological
      data on the incidence of the disease exist in Europe. In a prospective population
      based epidemiological study, all newly diagnosed cases of diabetes mellitus in
      patients under 15 years of age were registered nation-wide in Austria between
      1999 and 2001. Differential diagnosis (according to the American Diabetes
      Association diagnostic criteria) was based on clinical case definition. During
      the 3 years of the study period, 529 cases of DM <15 years were documented, of
      which 510 were clinically assigned to T1DM (271 boys, 239 girls) resulting in an
      incidence rate of 12.4/100,000. In the same network, eight cases were diagnosed
      as T2DM (one boy, seven girls) and two cases with an atypical form of T2DM (two
      girls). The age of onset of T2DM was 12-15 years and all patients were overweight
      (body mass index >90th percentile). The calculated incidence for T2DM <15 years
      in Austria was 0.25/100,000. CONCLUSION: at present, type 2 diabetes mellitus is
      rare but exists in children aged under 15 years in Austria. Follow-up of this
      registration will help to describe the secular trend.

PMID- 14569396
TI  - An update on the prevention of influenza in children and adolescents.
AB  - Influenza virus types A and B cause yearly outbreaks of respiratory tract
      infections in all age groups including children and adolescents. Complications,
      such as high fever, febrile convulsions, secondary bacterial infections and
      myositis frequently lead to hospitalisation. Safe and effective split, subunit
      and virosome vaccines are available from 6 months of age onwards. Most European
      countries do have guidelines for the use of influenza vaccines and current
      strategies primarily aim at decreasing the burden of influenza disease in
      certain, heterogeneously defined high risk groups. CONCLUSION: unfortunately,
      compliance of many physicians and patients with immunisation recommendations is
      rather poor and several barriers to immunisation have been identified. These
      deserve our specific attention in the future. Recently, neuraminidase inhibitors
      with curative and preventive efficacy against influenza virus types A and B have
      become available. They serve as second line weapons for influenza prophylaxis
      under specific circumstances.

PMID- 14569397
TI  - Rhabdomyolysis in a patient with Kawasaki disease.

PMID- 14569398
TI  - Reduced Fhit protein expression in human malignant mesothelioma.
AB  - Human malignant mesothelioma (MM) is an aggressive neoplasm related to
      occupational exposure to asbestos and characterised by a long latency time.
      Multiple chromosomal deletions and DNA losses have been revealed in MM by studies
      performed with karyotypic, comparative genomic hybridisation and loss of
      heterozygosity (LOH) analyses. Among frequently deleted chromosomal sites, LOH at
      chromosome 3p has been detected in MM, suggesting the presence of one or several
      tumour suppressor genes that have an important role in development of the
      disease. The FHIT (fragile histidine triad) tumour suppressor gene, located at
      3p14.2, has been proposed to be a target to major human lung carcinogens, such as
      tobacco smoke and asbestos. Although many studies have indicated decreased Fhit
      protein expression in a variety of malignancies, there is no report of FHIT gene
      aberrations or Fhit protein abnormalities in MM. We examined expression of the
      Fhit protein and LOH at the FHIT gene in malignant mesothelioma. Altogether, 13
      paraffin embedded MM tumours were analysed for Fhit protein expression, and 21
      fresh tumours and 10 cell cultures for LOH at the FHIT gene with two intragenic
      microsatellite markers. All tumours showed less intense immunostaining than
      normal bronchial epithelium or mesothelium. Fhit expression was absent or reduced
      in 54% (7 of 13) of the tumours, with the weakest staining observed in poorly
      differentiated areas. Allele loss was seen in 3 of 10 (30%) of the MM cell lines,
      but only in 1 of the 21 fresh tumours studied, suggesting concealment of LOH by
      normal cells present in MM tumours. In conclusion, our present data indicate a
      frequent decrease of Fhit protein expression, thus supporting the significance of
      FHIT inactivation in development of MM.

PMID- 14569399
TI  - The accuracy of volume estimates using ultrasound muscle thickness measurements
      in different muscle groups.
AB  - This study aimed to investigate the accuracy of estimating the volume of limb
      muscles (MV) using ultrasonographic muscle thickness (MT) measurements. The MT
      and MV of each of elbow flexors and extensors, knee extensors and ankle plantar
      flexors were determined from a single ultrasonographic image and multiple
      magnetic resonance imaging (MRI) scans, respectively, in 27 healthy men (23-40
      years of age) who were allocated to validation ( n=14) and cross-validation
      groups ( n=13). In the validation group, simple and multiple regression equations
      using MT and a set of MT and limb length, respectively, as independent variables
      were derived to estimate the MV measured by MRI. However, only the multiple
      regression equations were cross-validated, and so the prediction equations with
      r(2) of 0.787-0.884 and the standard error of estimate of 22.1 cm(3) (7.3%) for
      the elbow flexors to 198.5 cm(3) (11.1%) for the knee extensors were developed
      using the pooled data. This approach did not induce significant systematic error
      in any muscle group, with no significant difference in the accuracy of estimating
      MV between muscle groups. In the multiple regression equations, the relative
      contribution of MT for predicting MV varied from 41.9% for the knee extensors to
      70.4% for the elbow flexors. Thus, ultrasonographic MT measurement was a good
      predictor of MV when combined with limb length. For predicting MV, however, the
      unsuitability of a simple equation using MT only and the difference between
      muscle groups in the relative contribution of MT in multiple regression equations
      indicated a need for further research on the limb site selected and muscle
      analyzed for MT measurement.

PMID- 14569400
TI  - Breathing around the clock: an overview of the circadian pattern of respiration.
AB  - This article reviews human and animal studies about the circadian patterns of
      physiological variables involved with the respiratory function. Some measures
      reflecting the mechanical properties of the lungs, such as functional residual
      capacity, forced expiratory volumes and airway resistance, change periodically
      with the time of the day. Also resting pulmonary ventilation (V(E)), tidal
      volume, and breathing rate follow circadian patterns. In humans, these patterns
      occur independently of the daily changes in activity, whereas, to some extent,
      they are linked to changes in the state of arousal. Differently, in some rodents,
      the circadian oscillations of the breathing pattern occur independently of the
      daily rhythms of either activity or state of arousal. Recent measurements of the
      breathing pattern for unlimited periods of time in undisturbed animals have
      indicated that the circadian changes occur in close temporal phase with those of
      oxygen consumption, carbon dioxide production, and body temperature. However,
      none of these variables can fully explain the circadian pattern of breathing, the
      origin of which remains unclear. Both in humans and in rats the V(E) responses to
      hypercapnia or hypoxia differ at various times of the day. In rats, the daily
      differences in V(E) responses are buffered by changes in metabolic rate, such
      that, unlike humans, the hyperventilation (defined as the increase in ventilation
      metabolism ratio) remains constant throughout the 24 h. The presence of a
      biological clock is a major advantage in the adaptation to the environment,
      although it forces some variables to deviate periodically from their mean value.
      In humans, these deviations become apparent in conditions of hypoxia. Hence, a
      daily time-window exists in which the respiratory system is less capable of
      responding to challenges, a factor which may contribute to the findings that some
      cardio-respiratory symptoms and diseases peak at particular times of the day.

PMID- 14569401
TI  - The effect of physical and psychosocial loads on the trapezius muscle activity
      during computer keying tasks and rest periods.
AB  - The overall aim was to investigate the effect of psychosocial loads on trapezius
      muscle activity during computer keying work and during short and long breaks. In
      12 female subjects, surface electromyography (EMG) was recorded bilaterally from
      the upper trapezius muscle during a standardized one hand keying task-interspaced
      with short (30 s) and long (4 min) breaks-in sessions with and without a
      combination of cognitive and emotional stressors. Adding psychosocial loads to
      the same physical work did not increase the activity of the trapezius muscle on
      either the keying or the control side, both of which remained at median and
      static EMG activity levels of around 5% and 2.5% of the maximal voluntary
      electrical activity (EMG(max)), respectively. The difference between the keying
      and the control side was significant; and further the control side activity was
      significantly increased above resting level. During both short and long breaks,
      exposure to psychosocial loads also did not increase the activity of the
      trapezius muscle either on the side of the keying or the control hand. Of note is
      that during long breaks the muscle activity of the keying side as well as that of
      the control side remained at the same level as during the short breaks, which was
      increased above resting level. This was to be seen from the static and the median
      EMG activity levels as well as gap times, the overall mean values being:
      0.4%EMG(max), 1.1%EMG(max), and 50% in gap time, respectively. IN CONCLUSION:
      psychosocial loads are not solely responsible for increased non-postural muscle
      activity; and increasing the duration of breaks does not per se cause muscle
      relaxation.

PMID- 14569402
TI  - Validity of uniaxial accelerometry during activities of daily living in children.
AB  - The purpose of this study was to examine the validity of treadmill-based
      equations of two commonly used uniaxial accelerometers to estimate energy
      expenditure (EE) during activities of daily living in children. Twelve subjects
      with mean (SD) age11.4 (0.4) years engaged in a choreographed routine consisting
      of three activities (sweeping, bowling, and basketball) of 4min duration while
      wearing a Manufacturing Technology, Inc. (MTI) accelerometer, Caltrac
      accelerometer, and a portable gas analyzer (Cosmed K4b(2)). The equations of
      Trost et al. and Sallis et al. were used to convert activity counts to
      estimations of EE for the MTI and Caltrac, respectively. Correlation coefficients
      between Caltrac predictions of EE and measured EE from indirect calorimetry
      ranged from r=0.22 to 0.72 for individual activities. Correlations between MTI EE
      predictions and indirect calorimetry ranged from r=0.50 to 0.68 for individual
      activities. When the activities were pooled the correlations between EE from
      uniaxial accelerometers and EE from indirect calorimetry were moderately strong
      (MTI, r=0.78 and Caltrac, r=0.82). Inter-accelerometer (counts min(-1))
      correlations were 0.08, -0.54, 0.63, and 0.79 for sweeping, bowling, basketball,
      and pooled data, respectively. The overall mean difference, or bias, and 95%
      confidence intervals (CI) for each uniaxial accelerometer compared to indirect
      calorimetry were as follows: Caltrac, bias = 2.80 (2.36, 3.24) kcal min(-1); MTI,
      bias = 0.88 (0.23, 1.53) kcal min(-1). Both accelerometers significantly
      underestimated measured EE ( P<0.05). Uniaxial accelerometers provide potential
      for the measurement of physical activity (PA) and EE in children. Future studies
      refining accelerometry predictions of PA and EE are warranted.

PMID- 14569403
TI  - Caffeine induces a second wave of apoptosis after low dose-rate gamma radiation
      of HL-60 cells.
AB  - Most cell lines that lack functional p53 protein are arrested in the G(2) phase
      of the cell cycle due to DNA damage. It was previously found that the human
      promyelocyte leukemia cells HL-60 (TP53 negative) that had been exposed to
      ionizing radiation at doses up to 10 Gy were arrested in the G(2) phase for a
      period of 24 h. The radioresistance of HL-60 cells that were exposed to low dose
      rate gamma irradiation of 3.9 mGy/min, which resulted in a pronounced
      accumulation of the cells in the G(2) phase during the exposure period, increased
      compared with the radioresistance of cells that were exposed to a high dose-rate
      gamma irradiation of 0.6 Gy/min. The D(0) value (i.e. the radiation dose leading
      to 37% cell survival) for low dose-rate radiation was 3.7 Gy and for high dose
      rate radiation 2.2 Gy. In this study, prevention of G(2) phase arrest by caffeine
      (2 mM) and irradiation of cells with low dose-rate irradiation in all phases of
      the cell cycle proved to cause radiosensitization (D(0)=2.2 Gy). The irradiation
      in the presence of caffeine resulted in a second wave of apoptosis on days 5-7
      post-irradiation. Caffeine-induced apoptosis occurring later than day 7 post
      irradiation is postulated to be a result of unscheduled DNA replication and cell
      cycle progress.

PMID- 14569404
TI  - Carob pulp preparation rich in insoluble fibre lowers total and LDL cholesterol
      in hypercholesterolemic patients.
AB  - BACKGROUND: Recently, insoluble fibre from carob pulp has been found to affect
      blood lipids in animals in a similar manner as soluble dietary fibre. AIM OF THE
      STUDY: To investigate whether a carob pulp preparation containing high amounts of
      insoluble fibre has a beneficial effect on serum cholesterol in humans. METHODS:
      Volunteers (n = 58) with hypercholesterolemia were recruited to participate in a
      randomised, double- blind, placebo-controlled and parallel arm clinical study
      with a 6 week intervention phase. All participants consumed daily both, bread
      (two servings) and a fruitbar (one serving) either with (n = 29) or without (n =
      29) a total amount of 15 g/d of a carob pulp preparation (carob fibre). Serum
      concentrations of total, LDL and HDL cholesterol and triglycerides were assessed
      at baseline and after week 4 and 6. RESULTS: The consumption of carob fibre
      reduced LDL cholesterol by 10.5 +/- 2.2% (p = 0.010). The LDL:HDL cholesterol
      ratio was marginally decreased by 7.9 +/- 2.2 % in the carob fibre group compared
      to the placebo group (p = 0.058). Carob fibre consumption also lowered
      triglycerides in females by 11.3 +/- 4.5% (p = 0.030). Lipid lowering effects
      were more pronounced in females than in males. CONCLUSION: Daily consumption of
      food products enriched with carob fibre shows beneficial effects on human blood
      lipid profile and may be effective in prevention and treatment of
      hypercholesterolemia.

PMID- 14569406
TI  - Effect of carrot intake on cholesterol metabolism and on antioxidant status in
      cholesterol-fed rat.
AB  - BACKGROUND: Vegetables are major dietary sources of fibers and antioxidants such
      as carotenoids, polyphenols and vitamin C which contribute to explain their
      protective effects against cardiovascular diseases. AIM OF THE STUDY: We
      investigated in the rat the effects of a 3-week supplementation of the diet with
      carrot (15% dry matter) on lipid metabolism and antioxidant status. RESULTS: A
      significant decrease of cholesterol level in liver (-44%; P= 0.0007) was observed
      together with a reduction of the level of liver triglycerides (-40%; P= 0.0005).
      Fecal total steroids excretion increased by 30% upon feeding the carrot diet as
      compared to the control. The secretion of bile acids was maintained, whereas the
      cholesterol apparent absorption was reduced in rats fed carrot diet. Carrot
      consumption also improved the antioxidant status. It significantly decreased the
      urinary excretion of thiobarbituric acid reactive substances (TBARS), reduced the
      TBARS levels in heart, increased the vitamin E plasmatic level and tended to
      increase the ferric reducing ability of plasma (FRAP) as compared to the
      controls. The carrot diet provided carotenoid antioxidants: 5.1 mg beta-carotene,
      1.6 mg alpha-carotene and 0.25mg lutein per 100 g diet. No carotenoids were found
      in plasma whereas the three carotenoids were detected in the plasma of the rats
      fed the carrot diet at 125, 41, 43 nmol/L respective concentrations. beta
      Carotene was also detected in liver and heart. CONCLUSION: Carrot consumption
      modifies cholesterol absorption and bile acids excretion and increases
      antioxidant status and these effects could be interesting for cardiovascular
      protection.

PMID- 14569405
TI  - Fatty acid profiles, antioxidant status, and growth of preterm infants fed diets
      without or with long-chain polyunsaturated fatty acids. A randomized clinical
      trial.
AB  - Long-chain polyunsaturated fatty acids (LCP) are considered conditionally
      essential nutrients for the infant born prematurely, and attempts are being made
      to match fatty acid profiles of formula and breast fed infants. In this double
      blind, randomized study we investigated the effects of a formula enriched with
      both n-6 and n-3 LCP on plasma fatty acid profiles, antioxidant status and growth
      of premature infants. 29 infants received either a formula devoid of LCP or a LCP
      supplemented formula (0.5 g/100 g fat linoleic acid metabolites, 0.8 g/100 g fat
      alpha-linolenic acid metabolites). 17 breast fed infants served as a control
      group. At study entry as well as two and four weeks later, plasma and urine
      samples were collected, growth data obtained and food tolerance was documented.
      At the end of the four week study period, plasma docosahexaenoic acid (DHA)
      levels of supplemented infants were significantly higher than those of
      unsupplemented infants and similar to those of infants fed human milk. Plasma n-6
      LCP concentrations including arachidonic acid (AA) were similar between groups.
      The plasma alpha-tocopherol levels of breast fed and supplemented infants were
      similar and tended to be lower than in infants fed the formula devoid of LCP.
      Urinary malondialdehyde (MDA) excretion of formula fed infants was significantly
      higher compared to infants fed human milk, but did not differ between the two
      formula groups. Parameters of growth and milk tolerance did not differ between
      groups. Our results demonstrate that plasma LCP levels similar to those of breast
      fed infants can be achieved with the LCP supplemented formula used in this trial,
      without evidence of adverse effects of the LCP enrichment.

PMID- 14569407
TI  - Increased binding of LDL and VLDL to apo B,E receptors of hepatic plasma membrane
      of rats treated with Fibernat.
AB  - BACKGROUND: Research has focussed on the hypocholesterolemic effects of certain
      types of dietary fiber such as enhancing conversion of hepatic cholesterol to
      bile acids or increase in catabolism of low density lipoprotein (LDL) via the apo
      B,E receptor. AIM OF THE STUDY: The effect of oral administration of a unique
      fibre cocktail of fenugreek seed powder, guar gum and wheat bran (Fibernat) and
      its varied effects on some aspects of lipid metabolism and cholesterol
      homeostasis in rats were examined. METHODS: Rats were administered Fibernat along
      with the atherogenic diet containing 1.5 % cholesterol and 0.1 % cholic acid.
      Amounts of hepatic lipids, hepatic and fecal bile acids and activity of hepatic
      triglyceride lipase (HTGL) were determined. Transmission electron microscopic
      examination of the liver tissue and extent of uptake of (125)I-LDL and (125)I
      VLDL by the hepatic apo B,E receptor was carried out. RESULTS: Food intake and
      body weight gain were similar between the 3 different dietary groups. Fibernat
      intake significantly increased apo B,E receptor expression in rat liver as
      reflected by an increase in the maximum binding capacity (B(max)) of the apo B,E
      receptor to (125)I-LDL and (125)I-VLDL. The activity of HTGL was increased by
      approximately 1.5-fold in Fibernat-fed rats as compared to those fed the
      atherogenic diet alone. A marked hypocholesterolemic effect was observed.
      Cholesterol homeostasis was achieved in Fibernat-fed rats. CONCLUSION: Two
      possible mechanisms are postulated to be responsible for the observed
      hypocholesterolemic effect a) an increase in conversion of cholesterol to bile
      acids and b) possibly by intra-luminal binding which resulted in increased fecal
      excretion of bile acids and neutral sterols. The resulting reduction in
      cholesterol content of liver cells coupled with upregulation of hepatic apo B,E
      receptors and increased clearance of circulating atherogenic lipoproteins-LDL and
      very low density lipoprotein (LDL and VLDL)-is the main mechanism involved in the
      hypocholesterolemic effect of Fibernat. The results suggest that Fibernat's
      effect on plasma LDL concentration is also possibly mediated by increased
      receptor-mediated catabolism of VLDL. Thus, Fibernat therapy is an effective
      adjunct to diet therapy and might find potential use in the therapy of
      hyperlipidemic subjects.

PMID- 14569408
TI  - Long chain polyunsaturate supplementation does not induce excess lipid
      peroxidation of piglet tissues.
AB  - BACKGROUND: Addition of highly polyunsaturated fatty acids to infant formulas
      raises the possibility of increased lipid peroxidation. AIM OF THE STUDY: We
      determined the effects of increasing levels of dietary docosahexaenoic acid (DHA)
      and arachidonic acid (AA) on lipid peroxidation and peroxidative potential in
      piglet tissues. METHODS: Four groups of piglets (n = 6) were bottle-fed a formula
      containing one of four treatments: no long chain fatty acid (Diet 0) and three
      different levels of DHA/AA at 1-fold (0.3 %/0.6% FA; Diet 1) 2-fold (0.6 %/1.2%
      FA; Diet 2) and 5-fold (1.5%/3% FA; Diet 5) concentration used in some human
      infant formulas, and all with equal amount of vitamin E (5.7 IU/ 100 kcal
      formula) for four weeks. RESULTS: There were no significant differences between
      the groups in conjugated diene and glutathione (GSH) levels in the liver, and
      thiobarbituric acid-reactive substance (TBARS) in plasma. TBARS levels of the
      erythrocyte membranes increased in a dose-dependent manner when in vitro
      oxidation was induced with 10 mM hydrogen peroxide (H(2)O(2)) for 30 minutes. The
      TBARS levels of the liver homogenates of the Diet 5 and Diet 2 groups were
      significantly different than those of the membranes of the Diet 0 group when the
      in vitro oxidation was induced with H(2)O(2). CONCLUSION: The results show that
      dietary vitamin E effectively prevented lipid peroxidation at the LCP
      concentrations investigated and suggest that levels presently in infant formulas
      are sufficient.

PMID- 14569409
TI  - Maximal aerobic performance of deer mice in combined cold and exercise
      challenges.
AB  - In nature, animals frequently need to deal with several physiological challenges
      simultaneously. We examined thermoregulatory performance (body temperature
      stability) and maximal oxygen consumption of deer mice (Peromyscus maniculatus)
      during intense exercise at room temperature, acute cold exposure, and exercise
      during cold exposure. Results with exercise and cold exposure alone were
      consistent with previous studies: there was little difference between maximal
      metabolism elicited by exercise alone or cold exposure alone in warm-acclimated
      mice; after cold acclimation (9 weeks at 5 degrees C), maximal exercise
      metabolism did not change but maximum thermogenic capacity increased by >60%.
      Warm acclimated animals did not increase maximal oxygen consumption when exercise
      was combined with moderate cold (0 degrees C) and had decreased maximal oxygen
      consumption when exercise was combined with severe cold (-16 degrees C). Combined
      cold and exercise also decreased thermoregulatory performance and exercise
      endurance time. Cold acclimation improved thermoregulatory performance in
      combined cold and exercise, and there was also a slight increase in endurance.
      However, as for warm-acclimated animals, maximal exercise metabolism did not
      increase at low temperatures. We interpret these results as an indication of
      competition between thermoregulatory and locomotor effectors (brown adipose
      tissue and skeletal muscle) under the combined challenges of cold exposure and
      maximal exercise, with priority given to the locomotor function.

PMID- 14569410
TI  - Male contraception: mechanical, hormonal and non-hormonal methods.
AB  - There is a definite need for an effective and reversible form of male
      contraception, both for maintaining a stable population in industrial countries
      and for diminishing population growth in developing countries. It has been agreed
      upon that contraception is an essential component of reproductive health for men
      and women (the Weimar Manifesto on Male Contraception). The development of new,
      effective methods of male contraception has been identified as a high priority by
      the WHO Task Force on methods of regulation of male fertility. Hormonal male
      contraception is based on suppression of gondotrophins and substitution of
      testosterone in order to maintain male sexual function and bone mineralisation
      and to prevent muscle waist. For complete interruption of spermatogenesis, an
      adequate suppression of intratesticular testosterone production is needed.
      Various contraceptive regimens have been developed and tested, including
      testosterone monotherapy, androgen/progestin combinations, testosterone with GnRH
      analogs, and selective androgen and progestin receptor modulators. The
      combination of testosterone with progestogen is currently the most promising
      approach to hormonal male contraception. Also, several non-hormonal approaches to
      male contraception are promising and may offer the foundation for developing new
      male contraceptives.

PMID- 14569412
TI  - Individually weight-adapted examination protocol in retrospectively ECG-gated
      MSCT of the heart.
AB  - The standard protocol in multislice spiral CT (MSCT) angiography for coronary
      arteries with fixed tube current-time settings leads to an overexposure and thus
      to an unnecessary high radiation dose in patients with lower weight when compared
      to heavier patients. The purpose of this study was to estimate the effect of
      reducing the radiation dose by adapting the tube current-time settings
      individually. Fifty patients underwent retrospectively ECG-gated MSCT of the
      heart. In 25 patients (group A1) a standard protocol with constant tube current
      time settings was used (4 x 1-mm collimation, 120 kV, 400 mAs(eff)).
      Subsequently, artificial image noise was added to the data of these patients
      simulating a directive for weight-adapted tube current-time settings (group A2).
      In the other 25 patients (group B) an alternative protocol with individually
      weight-adapted tube current-time settings was applied. The data of all groups
      were evaluated by a regression analysis. The image quality was assessed
      objectively by measuring the CT attenuation in standardised regions of interest
      and subjectively by three radiologists using a five-point scoring system in a
      consensus reading. Applying the weight-adapted tube current-time settings the
      effective radiation dose was reduced by 17.9% for men and 26.3% for women. The
      standard protocol leads to an overexposure in light patients as seen in the plot
      of noise vs weight (slope 0.16+/-0.07 HU/kg). By applying the weight-adapted tube
      current-time settings a weight-independent, constant image noise is achieved
      (slope 0.04+/-0.1 HU/kg). Diagnostic image quality was preserved in all patients.
      Individually weight-adapted tube current-time settings allow for a substantial
      dose reduction when performing retrospectively ECG-gated MSCT angiography for
      coronary arteries without impairment of diagnostic image quality.

PMID- 14569411
TI  - Comment on Meller et al.: Value of F-18 FDG hybrid camera PET and MRI in early
      Takayasu aortitis.

PMID- 14569413
TI  - Morpho-histological study of somatic embryo-like structures in hypocotyl cultures
      of Pelargonium x hortorum Bailey.
AB  - Somatic embryo-like structures were produced from the hypocotyls of ten cultivars
      of Pelargonium x hortorum using the protocols of Marsolais et al. (1991; Can J
      Bot 69:1188-1193) and Slimmon et al. (1991; Plant Cell Rep 10:587-589) and their
      embryonic natures evaluated. Nine cultivars responded, and 937 structures were
      formed. Regeneration corresponded well with published data. The somatic embryo
      like structures were globular- to leaf-shaped or similar to shoots. A root pole
      was never visible. Histological examinations confirmed the lack of bipolarity and
      revealed vascular connections to the explant in the more developed structures.
      Therefore, these structures cannot be classified as somatic embryos. The
      importance of these results is discussed in terms of evaluating published
      protocols for the propagation of these pelargoniums by somatic embryogenesis from
      hypocotyls.

PMID- 14569414
TI  - Structure and function of the chloroplast signal recognition particle.
AB  - The targeting of proteins, including the insertion and translocation of proteins
      in or across membranes, is a fundamental process within a cell, and a variety of
      specialized mechanisms for protein transport have been developed during
      evolution. The signal recognition particle (SRP) is found in the cytoplasm of
      most, if not all, eukaryotes and prokaryotes where it plays a central role in the
      co-translational insertion of membrane proteins into the endoplasmic reticulum
      and plasma membrane, respectively. SRP is a ribonucleoprotein consisting of an
      RNA and at least one polypeptide of approximately 54 kDa (SRP54). Interestingly,
      chloroplasts contain a specialized type of signal recognition particle.
      Chloroplast SRP (cpSRP) contains a SRP54 homologue but differs strikingly from
      cytosolic SRP in various aspects of structure and function. In contrast to
      cytosolic SRP, it contains a novel protein subunit (cpSRP43) and lacks RNA. CpSRP
      is also distinctive in its ability to interact with its substrate, light
      harvesting chlorophyll a/ b-binding protein, post-translationally. Furthermore,
      it is remarkable that the 54 kDa subunit of cpSRP is also involved in the co
      translational transport of chloroplast-encoded thylakoid proteins, and is
      therefore able to switch between the co- and post-translational means of
      interaction with its respective substrate proteins.

PMID- 14569416
TI  - Evaluation of the antiangiogenic effect of Taxol in a human epithelial ovarian
      carcinoma cell line.
AB  - PURPOSE: Angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) are major ligands for
      the endothelium-specific tyrosine kinase receptor Tie-2 and are important
      regulators of endothelial cell survival. In the presence of vascular endothelial
      growth factor (VEGF), vessel destabilization by Ang-2 has been hypothesized to
      induce an angiogenic response, but in the absence of VEGF, Ang-2 leads to vessel
      regression. In the present study, a human ovarian cancer cell line was used to
      investigate the possibility that Taxol might affect the expression of Ang-1, Ang
      2, and VEGF. MATERIALS AND METHODS: KF 28, a single-cell clone of a human ovarian
      epithelial carcinoma cell line, was used. The expression of Ang-1, Ang-2, and
      VEGF was assessed by quantitative real-time RT-PCR and Western blot analysis or
      enzyme-linked immunosorbent assay. Conditioned medium was used in the in vitro
      angiogenesis assay. RESULTS: The concentration of Taxol that inhibited the growth
      of cells to the level of 50% of control cell growth was 4.65+/-0.35 nM.
      Quantitative real-time RT-PCR indicated that Ang-1 gene expression was
      significantly decreased by exposure to 2 nM Taxol for 168 h ( P<0.05 vs control
      cells). Western blot analysis confirmed that the Ang-1 protein level was
      decreased by exposure to 2 nM Taxol for 168 h. Ang-2 gene expression did not
      significantly differ between control cells and those exposed to Taxol for any of
      the indicated times. The Ang-1/ Ang-2 gene expression ratio was significantly
      decreased by exposure to Taxol for 168 h ( P<0.05 vs control cells). VEGF gene
      expression was significantly decreased by exposure to Taxol for 168 h ( P<0.05).
      The VEGF concentration in the conditioned medium was also significantly reduced
      by exposure to Taxol for 168 h ( P<0.05). Conditioned medium collected following
      Taxol treatment for 168 h significantly inhibited endothelial tubule formation (
      P<0.05). Cell growth did not significantly differ between control cells and those
      exposed to Taxol for any of the indicated times. CONCLUSIONS: Our results show
      that exposure of ovarian cancer cells to a low concentration of Taxol may inhibit
      the initiating event in angiogenesis, namely, vascular regression. This
      information might be valuable in the development of new therapeutic interventions
      for epithelial ovarian cancer.

PMID- 14569415
TI  - Isocitrate lyase of the yeast Kluyveromyces lactis is subject to glucose
      repression but not to catabolite inactivation.
AB  - KlICL1, encoding the isocitrate lyase of Kluyveromyces lactis, was isolated by
      complementation of the Saccharomyces cerevisiae icl1 deletion mutant. Sequence
      analysis revealed an open reading frame of 1626 nucleotides encoding a protein
      with 542 amino acids. The deduced protein shows extensive homologies to
      isocitrate lyases from various organisms, with an overall identity of 69% to the
      enzyme from S. cerevisiae. The KlICL1 gene has two major transcription start
      points, located at -113 bp and -95 bp relative to the ATG translation start
      codon. The gene is expressed on ethanol medium only in respiratory-competent
      cells. Transcription is repressed by glucose. Mutants carrying a Klcat8 deletion
      lack the ability to derepress KlICL1 transcription. A Klicl1 deletion mutant does
      not grow on ethanol medium and lacks any isocitrate lyase activity. A strain
      lacking the gene KlFBP1, which encodes the gluconeogenic enzyme fructose 1,6
      bisphosphatase, lacks the ability to grow on non-fermentable carbon sources. This
      implies that K. lactis does not contain additional isoenzymes catalyzing either
      of the reactions. Enzyme assays revealed that neither KlIcl1p nor KlFbp1p are
      subject to catabolite inactivation. However, the respective enzymes from S.
      cerevisiae are efficiently inactivated when expressed in K. lactis. Thus, despite
      the extensive sequence similarities of the enzymes involved, non-fermentative
      carbohydrate metabolism in the two yeasts displays distinct regulatory
      properties.

PMID- 14569417
TI  - Synergistic effects of co-administration of angiotensin 1-7 and Neupogen on
      hematopoietic recovery in mice.
AB  - PURPOSE: Angiotensin 1-7 [A(1-7)] is a seven amino acid peptide that has been
      shown to increase the proliferation of epidermal stem cells after dermal injury
      and the number of hematopoietic progenitors in the bone marrow of myelosuppressed
      mice. In this study, the effect of combining A(1-7) with Neupogen on
      hematopoietic recovery and bone marrow progenitors was evaluated. MATERIALS AND
      METHODS: Intravenous 5-fluorouracil (5FU) was administered to induce
      myelosuppression. Administration of A(1-7) and/or Neupogen was initiated 2 days
      after chemotherapy. Angiotensin II (AII) and A(1-7) binding were assessed by flow
      cytometric analysis. Hematopoietic progenitors were counted by colony forming
      assays. Recovery of formed elements in the blood was evaluated by hemocytometer.
      RESULTS: Flow cytometric analysis indicated that the number of early
      hematopoietic progenitors (Lin(-)Sca1(+)cKit(+)) that bind AII or A(1-7)
      increased 5-7 days after intravenous injection of 150 mg/kg 5FU. Further,
      administration of A(1-7) led to a slight increase in the number of circulating
      leukocytes and platelets after this chemotherapeutic regimen. When given in
      combination with a subclinical dose of Neupogen, a synergistic effect on the
      number of circulating leukocytes was observed, but there was no further effect on
      the number of circulating platelets. In myelosuppressed mice, A(1-7) had its most
      profound effect on the number of hematopoietic progenitors in the bone marrow.
      The progenitors evaluated in the study included BFU-E, CFU-Meg, CFU-GM and CFU
      GEMM. There was an increase in the number of these progenitors in the bone
      marrow, indicating an effect on all hematopoietic lineages. When given in
      combination with Neupogen, these effects were synergistic for the numbers of BFU
      E and CFU-Meg (Neupogen by itself had no effect) and for the myeloid progenitors
      at lower doses of A(1-7). CONCLUSIONS: These results suggest that these
      hematopoietic agents act at different sites within the hematopoietic cascade and
      that combining these two agents may be of benefit in the treatment of
      hematopoietic disorders.

PMID- 14569418
TI  - Molecular identification of pathogenic and nonpathogenic strains of Vibrio
      harveyi using PCR and RAPD.
AB  - Fifteen environmental samples of Vibrio spp. isolated from healthy and diseased
      shrimps were tested for pathogenicity to juvenile shrimps. Two isolates, strains
      Z2 and Z3, were observed to be pathogenic, causing 100% mortality of the target
      host compared to the control strain Vibrio harveyi ATCC 14126. Environmental and
      type strains were subjected to molecular characterization by restriction fragment
      length polymorphism (RFLP) and PCR using primers targeted to different virulence,
      transcriptional regulator, or quorum sensing genes from V. harveyi. Primers
      designed for luxN were specific and identified all the environmental strains as
      V. harveyi. The random amplified polymorphic DNA (RAPD) method was used to
      differentiate between pathogenic and nonpathogenic strains of V. harveyi. These
      methodologies allowed us to detect and distinguish strains virulent and avirulent
      to juvenile shrimp.

PMID- 14569419
TI  - Microbial characterization of free floating condensate aboard the Mir space
      station.
AB  - Three samples of humidity condensate that had accumulated behind panels aboard
      the Russian space station Mir were collected and returned to earth for analysis.
      As these floating masses of liquid come into contact with the astronauts and the
      engineering systems, they have the potential to affect both crew health and
      systems performance. Using a combination of culturing techniques, a wide variety
      of organisms were isolated included Escherichia coli, Serratia marcescens, and a
      presumed Legionella species. In addition, microscopic analysis indicated the
      presence of protozoa, dust mites, and spirochetes. These findings suggest the
      need for more comprehensive microbial analysis of the environment through the use
      of new methodologies to allow a more thorough risk assessment of spacecraft.

PMID- 14569420
TI  - Mass spectrometric method for the absolute calibration of the intramolecular
      nitrogen isotope distribution in nitrous oxide.
AB  - A mass spectrometric method to determine the absolute intramolecular (position
      dependent) nitrogen isotope ratios of nitrous oxide (N2O) has been developed. It
      is based on the addition of different amounts of doubly labeled 15N2O to an N2O
      sample of the isotope ratio mass spectrometer reference gas, and subsequent
      measurement of the relative ion current ratios of species with mass 30, 31, 44,
      45, and 46. All relevant quantities are measured by isotope ratio mass
      spectrometers, which means that the machines' inherent high precision of the
      order of 10(-5) can be fully exploited. External determination of dilution
      factors with generally lower precision is avoided. The method itself can be
      implemented within a day, but a calibration of the oxygen and average nitrogen
      isotope ratios relative to a primary isotopic reference material of known
      absolute isotopic composition has to be performed separately. The underlying
      theoretical framework is explored in depth. The effect of interferences due to
      14N15N16O and 15N14N16O in the 15N2O sample and due to 15N2+ formation are fully
      accounted for in the calculation of the final position-dependent nitrogen isotope
      ratios. Considering all known statistical uncertainties of measured quantities
      and absolute isotope ratios of primary isotopic reference materials, we achieve
      an overall uncertainty of 0.9 per thousand (1 sigma). Using tropospheric N2O as
      common reference point for intercomparison purposes, we find a substantially
      higher relative enrichment of 15N at the central nitrogen atom over 15N at the
      terminal nitrogen atom than measured previously for tropospheric N2O based on a
      chemical conversion method: 46.3 +/- 1.4 per thousand as opposed to 18.7 +/- 2.2
      per thousand. However, our method depends critically on the absolute isotope
      ratios of the primary isotopic reference materials air-N2 and VSMOW. If they are
      systematically wrong, our estimates will also necessarily be incorrect.

PMID- 14569422
TI  - The management of osteoporosis following hip fracture: have we improved our care?
AB  - To determine if physicians have improved the recognition and treatment of
      osteoporosis in patients with an acute hip fracture, we performed a retrospective
      analysis of discharge data from 1995 and 2000 at the University of Pittsburgh
      Medical Center, a large tertiary care, academic institution. We examined patients
      admitted with an acute hip fracture in 1995 and 2000 and age- and sex-matched
      patients admitted with community acquired pneumonia in 2000. Outcomes included
      age, gender, race, discharge diagnoses (from ICD-9 codes) and discharge
      medications (from discharge summaries) in all patients. There were 136 acute hip
      fracture patients (mean age 73+/-18 years) in 1995, 117 acute hip fracture
      patients (mean age 76+/-16 years) in 2000 and 116 patients with community
      acquired pneumonia (mean age 78+/-7 years). Patients admitted in 2000 with an
      acute hip fracture were more likely to be diagnosed with osteoporosis (18% vs.
      4%, P<0.02), more likely to be discharged on calcium (17% vs. 7%, P<0.02) and
      more likely to be discharged on antiresorptive therapy (15% vs. 2%, P<0.001) than
      those admitted in 1995. Moreover, patients admitted with community-acquired
      pneumonia were just as likely to receive calcium, vitamin D or antiresorptive
      agents at the time of discharge as those with an acute hip fracture in 2000.
      Patients with a diagnosis of osteoporosis in 2000 were older and more likely to
      receive antiresorptive agents than those without a diagnosis (29% vs. 11%,
      P<0.05). None of the patients received a bone mineral density examination while
      in the hospital. Although there was an improvement in the management of
      osteoporosis after an acute hip fracture from 1995 to 2000, there was no
      difference in management of patients with hip fracture versus pneumonia in the
      year 2000. However, patients with a "diagnosis" of osteoporosis in 2000 were more
      likely to be discharged on appropriate therapeutic options. We conclude that
      although we have improved our care of osteoporosis for elderly in general from
      1995 to 2000, patients with an acute hip fracture are not receiving any
      additional treatment unless they have a diagnosis of osteoporosis. Further
      studies are needed to determine which factors are needed to target patients for
      appropriate diagnosis and treatment.

PMID- 14569421
TI  - Cytochrome P450 3A and their regulation.
AB  - CYP3A isozymes collectively comprise the largest portion of the liver and small
      intestinal CYP protein and they are involved in the metabolism of 45-60% of all
      currently used drugs. In addition to drugs, CYP3A isozymes metabolise a variety
      of other compounds including steroid hormones, toxins and carcinogens. It is also
      well known that the hepatic expression and activity of CYP3A isozymes varies from
      individual to individual. The involvement of this variability in harmful
      interactions frequently encountered in development and application of drugs that
      are CYP3A substrates is well documented. It has also been postulated that
      variable CYP3A expression could affect an individual's predisposition to cancers
      caused by environmental carcinogens that are metabolised by CYP3A. The
      elucidation of factors controlling an individual's CYP3A activity could permit
      personalised dose adjustments in therapies with its substrates and may also
      possibly lead to the identification of sub-populations at increased risk for
      several common cancers. However, until recently, the development of markers
      predictive for the individual CYP3A expression has been slower than for other
      drug metabolising enzymes. Here we summarise the current status of our
      understanding of the genetics and regulation of the expression of CYP3A,
      including the recently described markers of the CYP3A5 and CYP3A7 polymorphisms.
      These latter markers are expected to speed up the development of activity probes
      for the individual CYP3A isozymes and to aid in our understanding of their
      individual functions.

PMID- 14569423
TI  - Epidemiology and outcome of acute lung injury in European intensive care units.
      Results from the ALIVE study.
AB  - OBJECTIVES: To re-examine the epidemiology of acute lung injury (ALI) in European
      intensive care units (ICUs). DESIGN AND SETTING: A 2-month inception cohort study
      in 78 ICUs of 10 European countries. PATIENTS: All patients admitted for more
      than 4 h were screened for ALI and followed up to 2 months. MEASUREMENTS AND MAIN
      RESULTS: Acute lung injury occurred in 463 (7.1%) of 6,522 admissions and 16.1%
      of all mechanically ventilated patients; 65.4% cases occurred on ICU admission.
      Among 136 patients initially presenting with "mild ALI" (200< PaO2/FiO2 < or
      =300), 74 (55%) evolved to acute respiratory distress syndrome (ARDS) within 3
      days. Sixty-two patients (13.4%) remained with mild ALI and 401 had ARDS. The
      crude ICU and hospital mortalities were 22.6% and 32.7% (p<0.001), and 49.4% and
      57.9% (p=0.0005), respectively, for mild ALI and ARDS. ARDS patients initially
      received a mean tidal volume of 8.3+/-1.9 ml/kg and a mean PEEP of 7.7+/-3.6
      cmH2O; air leaks occurred in 15.9%. After multivariate analysis, mortality was
      associated with age (odds ratio (OR) =1.2 per 10 years; 95% confidence interval
      (CI): 1.05-1.36), immuno-incompetence (OR: 2.88; Cl: 1.57-5.28), the severity
      scores SAPS II (OR: 1.16 per 10% expected mortality; Cl: 1.02-1.31) and logistic
      organ dysfunction (OR: 1.25 per point; Cl: 1.13-1.37), a pH less than 7.30 (OR:
      1.88; Cl: 1.11-3.18) and early air leak (OR: 3.16; Cl: 1.59-6.28). CONCLUSIONS:
      Acute lung injury was frequent in our sample of European ICUs (7.1%); one third
      of patients presented with mild ALI, but more than half rapidly evolved to ARDS.
      While the mortality of ARDS remains high, that of mild ALI is twice as low,
      confirming the grading of severity between the two forms of the syndrome.

PMID- 14569424
TI  - Lipopolysaccharide-binding protein: a possible diagnostic marker for Gram
      negative bacteremia in neutropenic cancer patients.
AB  - OBJECTIVE: Cancer patients with febrile neutropenia after chemotherapy have a
      variable risk of bacterial infection. Especially Gram-negative bacteremia is
      associated with high mortality and/or morbidity. Early diagnosis of patients with
      Gram-negative bacteremia at the onset of febrile neutropenia is potentially
      useful in tailoring therapy. DESIGN AND SETTING: Prospective study at the
      Department of Pediatric Oncology and Internal Medicine of a university hospital.
      PATIENTS: Were analyzed 66 febrile neutropenic episodes in 57 adults and
      children. Patients were divided into four groups: those with Gram-negative
      bacteremia, Gram-positive bacteremia, clinical sepsis, or fever of unknown
      origin. MEASUREMENTS AND RESULTS: Plasma lipopolysaccharide-binding protein (LBP)
      and C-reactive protein (CRP) concentrations were determined. LBP at the onset of
      febrile neutropenia was significantly higher in patients with Gram-negative
      bacteremia than those with fever of unknown origin and those with Gram-positive
      bacteremia. Using a cutoff value for LBP proved to have much greater sensitivity,
      specificity, and positive and negative predictive value for Gram-negative
      bacteremia than the best cutoff value for CRP. CONCLUSIONS: An initial high LBP
      level might predict Gram-negative bacteremia in cancer patients with febrile
      neutropenia. These results may have potential clinical impact by allowing therapy
      to be initiated for these patients at a very early stage.

PMID- 14569425
TI  - Parent, teacher and self-reported problem behavior in The Netherlands: comparing
      Moroccan immigrant with Dutch and with Turkish immigrant children and
      adolescents.
AB  - BACKGROUND: Although literature leaves little doubt that migration from one
      country to another is stressful, empirical studies do not warrant general
      conclusions regarding the impact of migration on psychological development.
      Moroccans and Turks are two of the largest immigrant groups in The Netherlands,
      and share a similar migration history and religion. However, there are important
      differences between Turkish and Moroccan society, for example, in the level of
      education and illiteracy. In this study, emotional and behavioral problems of
      Moroccan immigrant children were compared to those of Dutch native children and
      Turkish immigrant children. METHODS: Our samples consisted of 819 Moroccan
      immigrant children, 2,227 Dutch native children and 833 Turkish immigrant
      children between the age of 4 and 18. Parent, teacher and self-reports were
      obtained, using the Child Behavior Checklist, Teacher's Report Form and Youth
      Self-Report. RESULTS: Moroccan parents reported as many problems as Dutch
      parents, but less problems than Turkish parents. Teachers, however, presented a
      different picture: substantially more externalizing problems were reported for
      Moroccan pupils compared to Dutch and Turkish pupils. Moroccan adolescents
      themselves reported less problems than Dutch and Turkish adolescents.
      CONCLUSIONS: The effects of migration on children and adolescents of two
      populations with a similar migration history and religion can be rather
      different. Problem levels vary widely with the informant questioned. The results
      of the present study may reflect true differences in children's behavior, both
      across ethnic groups and across the contexts of home and school. Perceptual
      biases, social desirability in answering patterns and differences in thresholds
      to report problem behaviors may also be responsible for the observed differences.

PMID- 14569426
TI  - Location of independent root-knot nematode resistance genes in plum and peach.
AB  - Prunus species express different ranges and levels of resistance to the root-knot
      nematodes (RKN) Meloidogyne spp. In Myrobalan plum ( Prunus cerasifera), the
      dominant Ma gene confers a high-level and wide-spectrum resistance to the
      predominant RKN, Meloidogyne arenaria, Meloidogyne incognita, Meloidogyne
      javanica and the isolate Meloidogyne sp. Florida which overcomes the resistance
      of the Amygdalus sources. In Japanese plum ( Prunus salicina), a similar wide
      spectrum dominant resistance gene, termed R(jap), has been hypothesized from an
      intraspecific segregating cross. In peach, two crosses segregating for resistance
      to both M. incognita and M. arenaria were used to identify single genes that each
      control both RKN species in the Shalil ( R(Mia557)) and Nemared ( R(MiaNem))
      sources. Localisation of these genes was made possible using the RFLP and SSR-
      saturated reference Prunus map TxE, combined with a BSA approach applied to some
      of the genes. The Ma1 allele carried by the Myrobalan plum accession P.2175 was
      localised on the linkage group 7 at an approximate distance of 2 cM from the SSR
      marker pchgms6. In the Japanese plum accession J.222, the gene R(jap) was mapped
      at the same position in co-segregation with the SSR markers pchgms6 and CPPCT022.
      The peach genes R(Mia557) and R(MiaNem), carried by two a priori unrelated
      resistance sources, were co-localized in a subtelomeric position on linkage group
      2. This location was different from the more centromeric position previously
      proposed by Lu et al. (1999) for the resistance gene Mij to M. incognita and M.
      javanica in Nemared, near the SSR pchgms1 and the STS EAA/MCAT10. By contrast,
      R(Mia557) and R(MiaNem) were flanked by STS markers obtained by Yamamoto and
      Hayashi (2002) for the resistance gene Mia to M. incognita in the Japanese peach
      source Juseitou. Concordant results for the three independent sources, Shalil,
      Nemared and Juseitou, suggest that these peach RKN sources share at least one
      major gene resistance to M. incognita located in this subtelomeric position. We
      showed that plum and peach genes are independent and, thus, can be pyramided into
      interspecific hybrid rootstocks based on the plum and peach species.

PMID- 14569427
TI  - RAPD markers linked to eastern filbert blight resistance in Corylus avellana.
AB  - A total of 1,110 decamer primers were screened for RAPD markers linked to a
      dominant allele in hazelnut ( Corylus avellana) that confers resistance to
      eastern filbert blight caused by Anisogramma anomala. Twenty RAPD markers linked
      in coupling, and five markers linked in repulsion, were found. A seedling
      population was used to construct a linkage map of the region flanking the
      resistance locus. The map spans 46.6 cM, with 14 markers on one side of the
      resistance locus and eight on the other side. Eleven markers showed less than 3%
      recombination with resistance, including three that showed no recombination.
      Seven of these 11 markers are sufficiently robust to allow their use in marker
      assisted selection. These include AA12(850) which shows no recombination, and six
      markers on one side of the resistance locus: 173(500), 152(800), 122(825),
      275(1130), H19(650) and O16(1250). Marker 268(580), which flanks the resistance
      locus on the other side, is also suitable for use in marker-assisted selection,
      but shows 5.8% recombination with resistance. Other markers are less suitable for
      marker-assisted selection because of sensitivity to changes in primer or MgCl(2)
      concentration, or the long time required for electrophoresis to separate bands of
      similar size. The 16 markers closest to the resistance locus were cloned and
      sequenced. The W07(365) marker, which showed no recombination with the resistance
      locus but is difficult to score, includes a CT microsatellite repeat. The
      sequence information will allow the design of SCAR primers and eventual map-based
      cloning of the resistance allele.

PMID- 14569428
TI  - Distortion product otoacoustic emissions and auditory evoked potentials in the
      hedgehog tenrec, Echinops telfairi.
AB  - The hedgehog tenrec, Echinops telfairi, has certain basal mammalian features,
      like a cloaca and a sparsely differentiated brain with smooth cerebral
      hemispheres. The peripheral auditory capabilities of this species were
      investigated by means of distortion product otoacoustic emissions (DPOAE). For
      comparison, we determined auditory evoked potentials (AEP) in the inferior
      colliculus and the auditory cortex. Both methods show that the auditory range of
      E. telfairi extends well into ultrasonic frequencies, with a region of highest
      sensitivity at around 16 kHz. The total auditory range spans about 4 octaves at
      40 dB SPL. The low-frequency limit of auditory processing is found at frequencies
      of about 2-3 kHz. The DPOAE and the AEP thresholds of E. telfairi do not run
      fully parallel in the high-frequency range. For a threshold value of 40 dB SPL,
      cochlear mechanical thresholds as measured with DPOAE extend up to 50 kHz,
      whereas neuronal thresholds reach the high-frequency limit at about 30 kHz.
      Frequency tuning, as assessed from DPOAE suppression tuning curves, was low to
      moderate with Q(10 dB) values ranging from 1.7 to 8. The lack of discontinuity in
      the group delay (derived from DPOAE measurements) reveals that cochlear frequency
      representation is tonotopic without any region of specialized mechanical tuning.

PMID- 14569429
TI  - Neck muscle vibration alters visually perceived roll in normals.
AB  - The objective of this study was to determine whether vibration of dorsal neck
      muscles or of the mastoid bone or of both modified the perception of visual
      orientation in the head roll-tilt plane in normal subjects. Measurements of the
      subjective visual vertical (SVV) were obtained from 26 normal human subjects.
      Subjects reported the SVV in the upright and in the left and right 30 degrees
      static head roll-tilt positions. Subjects then reported the SVV while vibration
      was applied to the left or right dorsal neck or left or right mastoid. Both head
      position and vibration independently modified settings of the SVV. In head-tilted
      positions, vibration of the upper dorsal neck muscles (on the side of the head
      opposite to the head tilt) caused a significantly greater shift of the SVV in the
      opposite direction of head roll-tilt compared to vibration of the lower dorsal
      neck muscles or of the mastoid. These results support a role for cervical
      somatosensory information in perception of visual orientation in the roll plane.
      Our findings may help explain the differences observed in visual orientation
      perception in normal subjects between head alone and whole-body roll-tilt.
      Finally, vibration of neck muscles in the head roll-tilted plane may be a useful
      method to test cervical somatosensory function possibly by increasing their
      response to external stimulation.

PMID- 14569431
TI  - Acute thoracic aortic trauma: a comparison of endoluminal stent grafts with open
      repair and nonoperative management.
AB  - The magnitude of injury necessary to cause a traumatic aortic tear often results
      in high mortality. Open surgery in these patients is often not well tolerated.
      The purpose of this study was to compare the outcomes of three different
      treatment options in patients with traumatic aortic injuries. This was a
      retrospective review of a prospectively maintained computer database. Over a
      period of 33 months, 27 patients were diagnosed with thoracic aortic tears on the
      basis of a computed tomogram or a diagnostic angiogram. All patients were
      initially seen by trauma surgery staff and managed nonoperatively ( n = 12) if
      the predicted mortality due to associated injuries approached 100%. Thoracic
      surgery staff were consulted on all other patients, and open surgical repair was
      performed in 10 patients. Thoracic stent grafts were used in five patients
      because of inability to ventilate following an attempted thoracotomy ( n = 2) or
      associated organ injury that prohibited anticoagulation (head +/- liver injury, n
      = 3). Overall, patients in the endovascular group had a higher injury severity
      score than that of the open surgical group (42 +/- 9 vs. 32 +/- 11). However,
      mortality was lowest in the endovascular group (20%), higher in the open surgical
      group (50%), and highest in the nonoperative group (92%). No paraplegia was
      noted, and all surviving patients have been free of complications during the
      follow-up period. Due to the small number of patients in each treatment, no
      strong recommendations can be made. However, the results of thoracic stent grafts
      for patients with traumatic thoracic pseudoaneurysms may prove to be a safer and
      less invasive treatment option.

PMID- 14569430
TI  - Declining incidence of AIDS and increasing prevalence of AIDS presenters among
      AIDS patients in Italy.
AB  - Presented here are the results of a cohort study conducted on 3,483 consecutive
      HIV/AIDS patients between January 1993 and December 2000 to determine trends in
      AIDS incidence and presentation. The incidence of AIDS was calculated in the
      general population and examined further according to gender, age (< or = or >49
      years), and heterosexual behaviour as a risk factor for HIV. Multivariate
      analysis was used to identify variables associated with AIDS presenters (defined
      as patients diagnosed with AIDS within 1 month of the first HIV-positive test).
      The numbers of patients with AIDS classified as (i) AIDS presenters, (ii) known
      HIV-positive patients on antiretroviral treatment, and (iii) known HIV-positive
      patients not receiving antiretroviral treatment were calculated. The overall
      incidence of AIDS decreased over time, mainly due to the lower number of patients
      on antiretroviral treatment developing AIDS. Factors associated with a higher
      risk of being an AIDS presenter were male gender and year of HIV diagnosis. Among
      patients with AIDS, the proportion of AIDS presenters increased from 13.8% prior
      to 1997 (when protease inhibitors were introduced in Italy) to 32.5% after 1997.
      Variables predictive of being an AIDS presenter were male gender, age at
      diagnosis, and AIDS diagnosis in the years 1997-2000. Heterosexuals had a higher
      risk of being AIDS presenters and a lower risk of being HIV-positive and not
      receiving antiretroviral treatment than intravenous drug users. In Italy, AIDS
      occurs mainly in subjects unaware of their HIV status (especially males, the
      elderly, and those infected heterosexually) or in patients refusing
      antiretroviral therapy (mainly intravenous drug users who do not refer to
      specialised centres).

PMID- 14569432
TI  - The effects of intraoperative fenoldopam on renal blood flow and tubular function
      following suprarenal aortic cross-clamping.
AB  - This study evaluated the effect of fenoldopam, a selective dopamine (DA1)
      agonist, on renal blood flow and renal tubular function following renal ischemia
      induced by suprarenal aortic cross-clamping. Twenty anesthetized research pigs
      received either fenoldopam (10 micro g/kg/min; n = 10) or saline ( n = 10)
      beginning 20 min before suprarenal aortic cross-clamping and continuing for 20
      min after clamp release, for a total infusion time of 160 min (120-min cross
      clamp). Recordings of renal blood flow, mean arterial pressure, and heart rate
      were taken at baseline, during cross-clamping, and immediately postclamp.
      Ischemic renal injury was evaluated by serum creatinine and by histologic grading
      of acute tubular necrosis. Treatment with fenoldopam increased renal blood flow
      in comparison to that in the control group ( p = 0.03). The mean creatinine
      increase from baseline at 6 hr and 18 hr after cross-clamp removal for the
      fenoldopam-treated group was significantly less than that in the control group (
      p < 0.001). On histologic evaluation, the mean score for the degree of tubular
      necrosis was significantly higher in the control group ( p = 0.02), indicating
      less derangement of tubular morphology in the fenoldopam group. This study
      demonstrated that the intraoperative use of a continuous infusion of fenoldopam
      during suprarenal aortic cross-clamping results in increased renal blood flow,
      less postoperative rise in creatinine, and better preservation of tubular
      histology in the pig model.

PMID- 14569434
TI  - Hemodynamic stability during induction of anesthesia and tracheal intubation with
      propofol plus fentanyl, ketamine, and fentanyl-ketamine.
AB  - PURPOSE: This study was conducted to investigate hemodynamic and cardiac
      stability during anesthesia induction and intubation, using propofol plus
      fentanyl, propofol plus ketamine, and propofol plus fentanyl and ketamine.
      METHODS: Forty-five adult patients were randomly allocated to one of three groups
      according to the agents used for induction: propofol (2 mg/kg) plus fentanyl (3
      microg/kg) (PF), propofol (2 mg/kg) plus ketamine (0.1 mg/kg) (PK), and propofol
      (2 mg/kg) plus fentanyl (3 microg/kg) plus ketamine (0.1 mg/kg) (PFK).
      Hemodynamic responses were assessed by measuring changes in blood pressure (BP),
      heart rate (HR), and cardiac output (CO; using dye dilution combined with pulse
      dye densitometry [PDD]). RESULTS: BP and HR changes during the induction of
      anesthesia tended to be greater in the PK group than in the PF and PFK groups.
      After the injection of propofol, the cardiac index (CI) fell significantly below
      baseline values in the PF and PFK groups, but remained unchanged in the PK group.
      After tracheal intubation, BP and HR increased significantly only in the PF and
      PK groups, and reached a level significantly above baseline values only in the PK
      group. The CO responses to tracheal intubation were: PK group > PF group > PFK
      group. CONCLUSION: A combination of propofol plus fentanyl plus ketamine would
      provide greater reduction of fluctuations in hemodynamic variables associated
      with induction of anesthesia and tracheal intubation than combinations of
      propofol plus fentanyl or propofol plus ketamine.

PMID- 14569433
TI  - Recurrent stenosis and contralateral occlusion: high-risk situations in carotid
      endarterectomy?
AB  - Carotid angioplasty and stenting (CAS) has been proposed as a treatment option
      for carotid occlusive disease in high-risk patients including those with
      recurrent stenosis (RS) and contralateral occlusion (CO). This study reviews the
      results of carotid endarterectomy (CEA) in patients with RS and CO. We conducted
      a retrospective review from our vascular registry of 1670 patients who underwent
      CEAs ( n = 1950) from January 1990 through December 2001. Procedures included RS
      86 (4.4%), CO 112 (5.7%), and control 1752 (89.9%). There were 37 strokes in the
      entire group (1.9%). Among the high-risk group with RS and CO, there were 6
      strokes, (RS n = 2, CO n = 4) 3%. There were 31 strokes in the control group 1.8%
      ( p = NS). Postoperative TIAs were observed more frequently in patients with CO (
      n = 2) or RS ( n = 2), 1.8% and 2.3%, respectively ( p < 0.05). Neck hematomas,
      intracerebral hemorrhages, and myocardial infarctions did not differ between
      groups. Three deaths occurred within 30 days (0.15%); one was a patient with CO.
      Renal failure and symptomatic disease were each associated with a higher risk of
      perioperative stroke; among patients with renal failure there were 6 strokes
      (4.6%) p < 0.05, in symptomatic patients there were 26 strokes (2.7%) p < 0.05.
      Multivariate logistic regression analysis confirmed that preoperative renal
      disease and surgery for symptomatic disease were both significant predictors of
      perioperative stroke ( p < 0.05; odds ratio 2.177 and 2.943 respectively) while
      neither RS nor CO was from these results we concluded that the presence of RS and
      CO do not increase the risk of perioperative stroke in CEA.

PMID- 14569435
TI  - Decreased intraoral secretions during sedation-analgesia with propofol-ketamine
      and midazolam-ketamine combinations.
AB  - PURPOSE: To investigate salivary flow over time with a balanced sedation
      analgesia technique using a propofol-ketamine (PK) or a midazolam-ketamine (MK)
      combination in human volunteers. METHODS: In the PK group, boluses of 1 mg.kg(-1)
      of propofol and 0.7 mg.kg(-1) of ketamine were initially administered. This was
      followed by an infusion, given over a 1-h period, of propofol (5 mg.kg(-1))
      admixed with ketamine (0.7 mg.kg(-1)). In the MK group, 0.07 mg.kg(-1) of
      midazolam and 0.7 mg.kg(-1) of ketamine was followed by the infusion of a
      midazolam (0.07 mg.kg(-1)) and ketamine (0.7 mg.kg(-1)) admixture, also given
      over a period of 1 h. Salivary flow was measured prior to and at 10-min intervals
      during the sedation-analgesia, as well as for 30 minutes after its termination.
      RESULTS: Mixed intraoral secretions were significantly reduced, by 43% and 47%,
      on average, in the PK and MK groups, respectively, when compared with presedation
      levels, and had not returned to baseline levels 30 min after discontinuation of
      the infusion. CONCLUSION: Sedation-analgesia with PK and MK combinations controls
      intraoral secretions by reducing salivary flow.

PMID- 14569436
TI  - Efficacy of alkalinized lidocaine for reducing pain on intravenous and epidural
      catheterization.
AB  - PURPOSE: To investigate whether increasing the pH of lidocaine could reduce the
      pain caused by its skin infiltration as well as that caused by intravenous and
      epidural needle insertion. METHODS: A randomized, double-blind trial was
      undertaken in patients who were allocated to receive topical anesthesia with
      either plain (plain group; n = 25) or alkalinized lidocaine (alkalinized group; n
      = 25). An alkalinized lidocaine solution was prepared by adding 8.4% sodium
      bicarbonate to a plain 1% lidocaine solution at a ratio of 1 : 10. Pain was
      assessed using the verbal analog scale (VAS). RESULTS: In the alkalinized group,
      the VAS scores on skin infiltration in the hand (2.5 +/- 1.4) and the back (2.7
      +/- 1.4) were significantly lower than the respective scores in the plain group
      (3.5 +/- 1.4, and 4.9 +/- 1.9). Although the VAS score on intravenous needle
      insertion did not differ between the two groups, the VAS score on epidural needle
      insertion was significantly lower in the alkalinized group (1.3 +/- 1.0) than in
      the plain group (3.6 +/- 1.3). CONCLUSIONS: Alkalinization of lidocaine was
      effective in attenuating pain on skin infiltration and on epidural needle
      insertion.

PMID- 14569437
TI  - Tolerance to the analgesic effect of buprenorphine, butorphanol, nalbuphine, and
      cyclorphan, and cross-tolerance to morphine.
AB  - PURPOSE: The increased use of opioids in the chronic treatment of pain,
      especially with oncologic patients, encourages the search for drugs with potent
      analgesic activity, but with minimal induced tolerance and cross-tolerance to
      morphine. METHODS: Four agonist-antagonist opioid derivatives (buprenorphine,
      butorphanol, nalbuphine, and cyclorphan) were examined. Tolerance to the
      analgesic effect of the four drugs and their cross-tolerance effects with
      morphine were evaluated in ICR albino mice by the "hot plate method".
      Measurements of the analgesic effect were taken before and after chronic
      treatment (of 14 days duration) with these drugs, as well as morphine. RESULTS:
      All tested drugs produced tolerance after 14 days of treatment. Chronic treatment
      with morphine reduced the effects of nalbuphine and cyclorphan, but not those of
      buprenorphine and butorphanol. After 14 days treatment with buprenorphine and
      cyclorphan, the analgesic action of morphine was reduced, but this reduction did
      not occur after butorphanol and nalbuphine treatments. CONCLUSION: Of the four
      agonist-antagonists tested, butorphanol seems to be least likely to produce cross
      tolerance with morphine.

PMID- 14569438
TI  - Local infusion of nerve growth factor attenuates myelinated nerve fiber sprouting
      into lamina II of the spinal dorsal horn and reduces the increased responsiveness
      to mechanical stimuli in rats with chronic constriction nerve injury.
AB  - PURPOSE: To clarify the relationship between allodynia and the sprouting of
      myelinated fibers, we examined whether the administration of nerve growth factor
      (NGF) affected the paw withdrawal response to non-noxious mechanical stimuli and
      the sprouting of myelinated fibers into lamina II of the spinal dorsal horn,
      using a chronic constriction injury model of the sciatic nerve. METHODS:
      Mechanical allodynia was determined as the threshold of the withdrawal response
      stimulated by von Frey filaments. Sprouting was examined using horseradish
      peroxidase conjugated to the B fragment of cholera toxin (B-HRP). NGF was
      continuously infused into the site of nerve injury for 14 days after nerve
      ligation. RESULTS: With vehicle infusion, significantly increased responsiveness
      to mechanical stimuli was observed on postoperative days (PODs) 5, 7, and 14
      after ligation, compared with before surgery, and B-HRP-positive fibers were
      newly localized in lamina II on PODs 7 and 14. Infusion of NGF reduced the
      responsiveness to mechanical stimuli on 5, 7, and 14 PODs and B-HRP-positive
      fibers in lamina II on PODs 7 and 14. CONCLUSION: We propose that the suppression
      of the increased responsiveness to mechanical stimuli produced by NGF could be
      related to the disappearance of B-HRP-positive fibers in lamina II.

PMID- 14569439
TI  - Maternal treatment with NMDA receptor antagonist (MK-801) attenuates delayed
      mitochondrial dysfunction after transient intrauterine ischemia in the neonatal
      rat brain.
AB  - PURPOSE: Mitochondrial respiratory activities were measured in neonatal rat
      brains to evaluate the influence of transient intrauterine ischemia on the near
      term fetus and to assess the effect of dizocilpine maleate (MK-801), a
      noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist. METHODS:
      Transient intrauterine ischemia was induced by 30 min of right uterine artery
      occlusion at 17 days of gestation in Wistar rats. Vehicle (saline) or 0.5 mg/kg
      of MK-801 was administered after 1 h of recirculation. All of the pups were
      delivered by cesarean section at 21 days of gestation and samples of cerebral
      cortical tissue were obtained from pups at 1 h after birth. Adenosine diphosphate
      (ADP)-stimulated, nonstimulated, and uncoupled respirations were measured
      polarographically in homogenates. The respiratory control ratio was defined as
      ADP-stimulated divided by non-stimulated respiration. RESULTS: In the vehicle
      treated group the neonatal cortical tissue exposed to ischemia showed a
      significant decrease in ADP-stimulated respiration and respiratory control ratio
      compared with these findings in normoxic control animals. The delayed
      mitochondrial respiratory dysfunction was prevented by MK-801, given 1 h after
      the start of recirculation (P < 0.05). CONCLUSION: The present results indicate
      that transient intrauterine ischemia in the near-term rat fetus is associated
      with delayed mitochondrial dysfunction in the neonatal brain; the results suggest
      that maternal treatment with MK-801 attenuates the deterioration, even when
      administered 1 h after the start of recirculation.

PMID- 14569440
TI  - Current prevention and treatment of postoperative nausea and vomiting with 5
      hydroxytryptamine type 3 receptor antagonists: a review.

PMID- 14569441
TI  - Cerebral air embolism complicating percutaneous thin-needle biopsy of the lung:
      complete neurological recovery after hyperbaric oxygen therapy.

PMID- 14569442
TI  - A simple way to prevent infection from removed laryngeal mask airways.

PMID- 14569443
TI  - Amniotic fluid embolism.

PMID- 14569444
TI  - Significance of multicentric cancer recurrence after potentially curative
      ablation of hepatocellular carcinoma: a longterm cohort study of 892 patients
      with viral cirrhosis.
AB  - BACKGROUND: Tumor recurrence is common after potentially curative ablation of
      hepatocellular carcinoma; therefore, the incidence of intrahepatic metastasis and
      multicentric carcinogenesis was evaluated. METHODS: A cohort of 892 patients with
      cirrhosis caused by either hepatitis B virus (n=246) or hepatitis C virus (n=646)
      was followed up without interferon administration. RESULTS: Hepatocellular
      carcinogenesis rates were 28.0% at the end of the fifth year, 49.2% at the tenth
      year, and 61.3% at the fifteenth year. Sex, hepatitis virus, alpha-fetoprotein,
      platelet count, age, and indocyanine green retention test value significantly
      affected the carcinogenesis rate. Of 372 patients with tumor development, 162
      (43.5%) received surgical or radical locoregional therapy. On the assumption that
      a second carcinogenesis after sufficient ablation of well-differentiated cancer
      was attributable to multicentric carcinogenesis, recurrence rates after curative
      therapy in all the 162 patients, and the recurrence rates in 39 patients with
      solitary, small, and well-differentiated histology were analyzed: the rates were
      58.2% and 30.9% at the third year, 75.9% and 53.4% at the fifth year, and 89.6%
      and 79.9% at the tenth year, respectively. The estimated incidence of
      multicentric recurrence was, therefore, 31% or higher at the third year and 53%
      or higher at the fifth year. The actual second carcinogenesis rates (multicentric
      recurrence) were approximately 1.6 times as high as those of the virtual second
      carcinogenesis rates calculated from statistical simulation. CONCLUSIONS: A
      longterm cohort study disclosed that multicentric carcinogenesis was the
      principal mechanism of recurrence after curative ablation of hepatocellular
      carcinoma and that the concept of "carcinogenic stage" should be introduced to
      improve the understanding of carcinogenic events in viral cirrhosis.

PMID- 14569445
TI  - Risk of HCV transmission after needlestick injury, and the efficacy of short
      duration interferon administration to prevent HCV transmission to medical
      personnel.
AB  - BACKGROUND: We carried out this study to assess the risk of hepatitis C virus
      (HCV) transmission after needlestick injuries in medical personnel, and to
      evaluate the efficacy of short-duration interferon administration to prevent HCV
      transmission. METHODS: A total of 684 personnel who had been occupationally
      exposed to an anti-HCV-positive source and followed for more than 3 months were
      retrospectively examined. RESULTS: Of the 684 subjects, 279 (41%) were treated
      with 1 to 3 days of interferon either just after or 1 to 12 days after the
      injury. One case of HCV infection was found in each of the treated (1/279; 0.4%)
      and nontreated (1/405; 0.2%) groups. There was no significant difference in the
      transmission of HCV between the two groups. Both infected patients were treated
      with interferon after developing acute hepatitis, and HCV was subsequently
      cleared. CONCLUSIONS: There is a lower risk of HCV transmission after needlestick
      accident than previously reported, and short-duration interferon administration
      at an early stage after the needlestick injury, to prevent HCV transmission, is
      unnecessary.

PMID- 14569446
TI  - Pneumothorax during laparoscopy.
AB  - BACKGROUND: Pneumothorax is a known complication of laparoscopy, with most
      pneumothoraces diagnosed postoperatively with conventional chest x-ray.
      Electrocardiogram (ECG) conduction changes are associated with pneumothorax. In a
      sheep model, ECG changes were evaluated as a potential indicator of
      intraoperative pneumothorax. Additionally, resolution rates of helium (He) and
      carbon dioxide (CO2) pneumothorax were also evaluated in this model. METHODS:
      Under general anesthesia, 10 sheep had known volumes (20-100 cc) of either He or
      CO2 introduced into the left hemithorax. A 12-lead ECG recorded changes
      associated with the induced pneumothorax. After changes in the ECG plateaued, the
      gas volume in the hemithorax was increased to 2 L and the resultant pneumothorax
      was followed for a 2-h period using fluoroscopy to determine resolution rates for
      the different gas pneumothoraces. Gas volumes were aspirated after 2 h and ECGs
      were again recorded. RESULTS: Pneumothorax volumes as low as 20 cc produced
      consistent ECG changes. The amplitude of the precordial QRS complex was seen to
      diminish, and this lowering of the QRS amplitude continued as pneumothorax volume
      increased up to 100 cc. The ECG returned to prepneumothorax patterns with
      aspiration of the left chest. For different gas pneumothoraces, CO(2)
      pneumothorax showed almost complete resolution in the 2-h period, whereas He
      pneumothorax was unchanged. CONCLUSIONS: Precordial ECG changes appear to be a
      very sensitive indicator of pneumothorax, with very small pneumothorax (<100 cc)
      consistently being detected by reduction of the QRS complex amplitude.
      Intraoperative use of precordial ECG leads could result in rapid identification
      of pneumothorax during laparoscopic surgery. Carbon dioxide pneumothorax shows
      near 100% resolution in a 2-h period. This supports recommendations of expectant
      management in asymptomatic patients with CO(2) pneumothorax. However, He
      pneumothorax does not resolve spontaneously quickly and may require aspiration
      even in asymptomatic patients.

PMID- 14569447
TI  - Circumferential mucosectomy with stapled proctopexy is a safe, effective
      outpatient alternative for the treatment of symptomatic prolapsing hemorrhoids in
      the elderly.
AB  - BACKGROUND: Circumferential mucosectomy with stapled proctopexy (CMSP) was first
      introduced in 1993 as a less painful and highly effective alternative to
      traditional operative hemorrhoidectomy. Although CMSP has many advantages over
      traditional hemorrhoidectomy, some authorities and insurers continue to regard it
      as an inpatient procedure and others have been slow to adopt this progressive
      technique. This study documents the safe and effective outpatient nature of this
      procedure. METHODS: From December 2001 through August 2002, 33 patients with
      mucosal prolapse and prolapsing internal hemorrhoids were treated using
      circumferential mucosectomy with stapled proctopexy as outpatients at an
      ambulatory surgery center. Fourteen (42%) patients were treated using local
      anesthesia with intravenous sedation, 18 (55%) chose spinal anesthesia, and
      general anesthesia was used in one patient. Patients were evaluated
      postoperatively by telephone at 1 and 2 weeks, and seen in clinic at 4 weeks.
      RESULTS: One patient (3%) required an emergency department visit for minor
      postoperative bleeding. None of our elderly patients required emergency
      department evaluation and none reported significant complications. Four patients
      (13%) required urinary catheter placement prior to discharge from the surgery
      center due to urinary retention. One patient (3%) developed an uncomplicated
      urinary tract infection, which resolved with antibiotic treatment. Two patients
      were seen earlier than 4 weeks at the surgeon's request; one was
      immunocompromised from chemotherapy for metastatic carcinoid, and one reported
      persistent pain during initial telephone follow-up. No complications were
      identified in either patient, and no additional complications have been noted to
      date. CONCLUSIONS: CMSP is a safe, effective, time-efficient procedure for
      patients with mucosal prolapse and prolapsing hemorrhoids that can be performed
      safely in the ambulatory surgery center setting. Age is not a limiting factor in
      selecting patients for this safe outpatient procedure.

PMID- 14569448
TI  - Peritoneal macrophage and blood monocyte functions after open and laparoscopic
      assisted cecectomy in rats.
AB  - BACKGROUND: It has been well established that open abdominal surgery results in
      systemic immunosuppression postoperatively; in contrast, laparoscopic surgery is
      associated with significantly better preserved systemic immune function. However,
      when intraperitoneal (local) immune function is considered, laparoscopic
      procedures done under a CO2 pneumoperitoneum (pneumo) have been shown to result
      in greater immunosuppression compared to that of open surgery. Few studies have
      simultaneously assessed systemic and local immune function. The purpose of this
      study was to assess peripheral blood mononuclear cell (PBMC) and peritoneal
      macrophage tumor necrosis factor-alpha (TNF-alpha) levels, H2O2 production, and
      MHC class II antigen expression after open and laparoscopically assisted
      cecectomy in a rat model. METHODS: A total of 75 Sprague Dawley rats were used
      for three separate experiments. For each study, rats were randomly divided into
      three groups: anesthesia alone (AC), laparoscopic-assisted cecectomy (LC), and
      open cecectomy via full laparotomy (OP). A CO2 pneumo was used for laparoscopic
      operations. On postoperative day 1 the animals were sacrificed, macrophages were
      harvested via intraperitoneal lavage, and PBMCs were isolated from whole blood
      obtained by cardiac puncture. In experiment 1, macrophages and PBMC from each
      animal were stimulated with lipopolysaccharide, after which TNF-alpha levels of
      the supernatant were determined. In experiment 2, after stimulation with PMA,
      H2O2 release was assessed by measuring fluorescence. In experiment 3, via flow
      cytometry, the number of cells with surface MHC class II proteins were
      determined. Data from the three groups in each experiment were compared using
      analysis of variance Tukey-Kramer tests. RESULTS: Macrophages and PBMC from rats
      in the OP group released significantly more TNF-alpha than cells from rats in the
      LC ( p < 0.05) or AC ( p < 0.05) groups. Macrophages from rats in the OP group
      released significantly less H2O2 than cells from the AC ( p < 0.01) and LC ( p <
      0.05) groups. There was no difference between the AC and LC results. No
      significant differences in PBMC H2O2 release were noted among any of the groups.
      OP group macrophages expressed significantly less MHC class II antigen than did
      AC group macrophages ( p < 0.05). No differences were noted among the LC results
      and either the OP or AC group's outcomes. No differences were noted in PBMC MHC
      class II expression among any of the groups. CONCLUSIONS: In all instances, the
      LC group's macrophage results were similar to the AC group's results. OC group
      macrophages produced significantly more TNF-alpha and less H2O2 than both the AC
      and LC groups. MHC class II protein expression was less for the OC group than for
      the AC group. OC group PBMCs produced more TNF-alpha. No differences in PBMC H2O2
      release or MHC class II expression were noted. Laparoscopic methods better
      preserves the baseline values of the parameters studied.

PMID- 14569450
TI  - Colonoscopy: why are general surgeons being excluded?
AB  - BACKGROUND: The role of surgeons as endoscopists has been extensively debated in
      the literature, with conflicting studies published regarding the safety and
      efficacy of surgeons performing colonoscopies. A multitude of medical federations
      and societies have set various standards for granting endoscopy privileges, many
      with a bias against general surgeons [1, 3]. We reviewed the colonoscopy
      experience at our institution to evaluate differences between gastroenterologists
      (GI) and general (GS) and colorectal surgeons (CRS) in procedure times and
      complication and cecal intubation rates. METHODS: Between January 2000 and July
      2002, 5237 colonoscopies were performed at our institution. The data for
      procedure times, completion, and complication rates were collected in a
      prospective database. Complications were defined as perforation, bleeding, and
      postpolypectomy syndrome. Incomplete colonoscopies due to colitis, poor bowel
      preparation, or tumor obstruction were excluded. Chi-squared test was used to
      compare complication and cecal intubation rates between the three groups. Median
      procedure times were compared using the Kruskall-Wallis and Dunn's pairwise
      tests. A significant p-value was defined as <0.05. RESULTS: No differences in the
      complication rate was noted between the three groups: GI (0.12%), CRS (0.15%),
      and GS (0.11%) ( p = 0.99). There was a trend toward a lower incomplete
      colonoscopy rate in the GS group compared to CRS and GI: 0.32% vs 0.84% and
      0.36%, respectively ( p = 0.07). The median colonoscopy times for GS (29 min),
      however, were shorter than for GI (34 min, p < 0.001) or CRS (31 min, p < 0.001).
      CONCLUSION: General surgeons perform colonoscopies expeditiously, with as low a
      morbidity rate and as high a completion rate as their gastroenterology or
      colorectal surgery colleagues. As the results of this study confirm, general
      surgeons should not be excluded from endoscopy suites.

PMID- 14569449
TI  - Laparoscopic Roux-en-Y pancreatic cyst-jejunostomy.
AB  - BACKGROUND: The surgical management of pancreatic pseudocysts can be established
      through a variety of techniques. Internal drainage has consistently proven to be
      the treatment of choice for both acute and chronic pancreatic pseudocysts. With
      the growing popularity of minimally invasive surgery and improvements in surgical
      technique, laparoscopic internal drainage procedures for pancreatic pseudocysts
      are being attempted. While most authors have focused on laparoscopic cyst
      gastrostomies, few have written about laparoscopic cyst-jejunostomies. METHODS:
      In this article, we report our experience with eight laparoscopic Roux-en-Y cyst
      jejunostomies. Of the eight patients, six had alcoholic pancreatitis, and two had
      gallstone pancreatitis. There were five men and three women with a mean age of 48
      (range 35-71 years). RESULTS: The mean operative time was 150 min, with a range
      of 100-215 min. We report a mean EBL of 78 cc, a minor complication rate of 20%,
      and no major complications or mortalities. CONCLUSIONS: These data compare
      favorably with both open and laparoscopic internal drainage procedures.
      Laparoscopic cyst-jejunostomy offers a feasible alternative in the minimally
      invasive management of pancreatic pseudocyst.

PMID- 14569451
TI  - Screening colonoscopy in the asymptomatic 50- to 59-year-old population.
AB  - BACKGROUND: In an effort to decrease the death rate from colorectal cancer, a
      multitude of medical societies and task forces recommend routine screening for
      colorectal cancer beginning at age 50. Yet, there is no consensus as to the best
      and most cost-effective screening method. Medicare now pays for screening
      colonoscopies for its average risk beneficiaries [3]. Many insurance companies,
      however, will not cover this test in younger patients. We therefore reviewed our
      institution's colonoscopy experience with asymptomatic 50- to 59-year-olds, with
      negative fecal occult blood tests and negative family histories. METHODS: Between
      January 1999 and January 2002, 4779 colonoscopies were performed at our
      institution. The charts for 619 persons 50-59 years of age were retrospectively
      reviewed, with 91 patients meeting the strict requirements of this study. We
      defined polyps with high-grade neoplasias as those with villous or tubulovillous
      components, and cancerous lesions included those with carcinoma in situ. The
      distal colon was defined as the rectum and sigmoid colon. RESULTS: There was a
      58% incidence of neoplastic polyps in this younger asymptomatic population. More
      than 4% of our subjects had high-grade neoplasias or cancerous lesions. In the
      absence of any distal findings, flexible sigmoidoscopy would have missed up to
      38% of these polyps. CONCLUSIONS: The findings generally support the
      recommendations by the American College of Gastroenterology for average-risk
      patients to preferentially undergo a screening colonoscopy at age 50 in lieu of
      other methods.

PMID- 14569452
TI  - Laparoscopic versus open nephrectomy in 210 consecutive patients: outcomes, cost,
      and changes in practice patterns.
AB  - BACKGROUND: Initially slow to gain widespread acceptance within the urological
      community, laparoscopic nephrectomy is now becoming the standard of care in many
      centers. Our institution has seen a dramatic transformation in practice patterns
      and patient outcomes in the 2 years following the introduction of laparoscopic
      nephrectomy. We compare the experience with laparoscopic and open nephrectomy
      within a single medical center. METHODS: Data were collected for all patients
      undergoing elective nephrectomy (live donor, radical, simple, partial, and
      nephroureterectomy) between August 1998 and September 2002. Data were analyzed by
      Wilcoxon rank sum, chi-square, and Fisher's exact test. A p-value <0.05 was
      considered significant. RESULTS: Of the patients, 92 underwent open nephrectomy,
      and 118 were treated laparoscopically (87 hand-assisted laparoscopic nephrectomy,
      31 totally laparoscopic). There was one conversion (0.8%). Patient demographics
      and indications for surgery were equivalent for both groups. Mean operative time
      for laparoscopic nephrectomy (230 min) was longer than for open (187 min, p =
      0.0001). Blood loss (97 ml vs 216 ml, p = 0.0001), length of stay (3.9 days vs
      5.9 days, p = 0.0001), perioperative morbidity (14% vs 31%, p = 0.01), and wound
      complications (6.8% vs 27.1%, p = 0.0001) were all significantly less for
      laparoscopic nephrectomy. For live donors, time to convalescence was less (12
      days vs 33 days, p = 0.02), but hospital charges were more for patients treated
      laparoscopically (19,007 dollars vs 13,581 dollars, p = 0.0001). CONCLUSIONS:
      Laparoscopic nephrectomy results in less blood loss, fewer hospital days, fewer
      complications, and more rapid recovery than open surgery. We believe that these
      benefits outweigh the higher hospital charges associated with the laparoscopic
      approach.

PMID- 14569453
TI  - Laparoscopic treatment of post renal transplant lymphoceles.
AB  - BACKGROUND: Traditionally, a post transplant lymphocele (PTL) is drained by
      widely opening the wall connecting the lymphocele cavity to the intraperitoneal
      space via laparotomy. We hypothesize that laparoscopic techniques can be
      effectively used for the treatment of PTL. METHODS: Patients requiring
      intervention for PTL between 1993 and 2002 were identified via a retrospective
      review. Results of drainage via laparotomy and laparoscopy were compared.
      RESULTS: During the study period 685 renal transplants (391 cadaveric, 294
      living) were performed. The incidence of lymphocele was 5% [34/685 (36 cases)].
      The indications for surgical drainage were local symptoms (69%), graft
      dysfunction (14%), or both (17%). The mean time to surgical therapy was 4.9
      months. Laparoscopic drainage was performed in 25 patients (74%) and open
      drainage in 9 patients (26%). Open procedures were performed in cases for:
      previous abdominal surgery (5), undesirable lymphocele characteristics or
      location (2), or with concomitant open procedures (3). There were no conversions
      or operative complications in either group. There was no difference in operative
      time for the laparoscopic group vs the open group (108 +/- 6 vs 123 +/- 18 min, p
      = 0.8). Hospital stay was significantly shorter for the laparoscopic group (1.7
      +/- 0.8 vs 3.8 +/- 1.0, p = 0.0007), with 88% of laparoscopic patients being
      either overnight admissions or same day surgery. Two patients (5%) developed
      symptomatic recurrences requiring reoperation [1 laparoscopic (4%), 1 open
      (10%)]. CONCLUSIONS: Laparoscopic fenestration of a peritransplant lymphocele is
      a safe and effective treatment. The large majority of patients treated with
      laparoscopic fenestration were discharged within one day of surgery. Unless
      contraindications exist, laparoscopy should be considered first-line therapy for
      the surgical treatment of posttransplant lymphocele.

PMID- 14569454
TI  - The intercollegiate Basic Surgical Skills Course.
AB  - OBJECTIVE: This study was undertaken to establish residents' progress in minimal
      access surgery (MAS) after attending the Intercollegiate Basic Surgical Skills
      Course (BSSC) by means of the Xitact LS500 laparoscopy simulator assessment
      program. METHODS: Twenty-five surgical residents attended the BSSC in Leiden and
      Eindhoven, The Netherlands. Before and after the course, participants performed
      three "runs" on the Xitact LS500, featuring a standardized laparoscopic
      cholecystectomy clip-and-cut task. A control group of 25 interns not attending
      the course also performed two sessions of three runs. Parameters of interest were
      "score" and "time for completion of task". RESULTS: No significant differences
      were found within the resident group for the parameters "time" and "score" when
      comparing outcomes pre- and post-BSSC. No significant differences were found
      comparing time and score between residents and interns on each of the six runs,
      except for time in run 2. Over six runs, both residents and interns became
      significantly faster. CONCLUSIONS: The Xitact LS500 cholecystectomy simulator did
      not detect significant improvement in MAS performance among a group of surgical
      residents attending the BSSC.

PMID- 14569455
TI  - Laparoscopic cholecystectomy in patients with previous upper or lower abdominal
      surgery.
AB  - BACKGROUND: Previous abdominal surgery has been reported as a relative
      contraindication to laparoscopic cholecystectomy. This study specifically
      examined the effect of previous intraabdominal surgery on the feasibility and
      safety of laparoscopic cholecystectomy. METHODS: Data from 1,638 consecutive
      patients who underwent laparoscopic cholecystectomy were reviewed and analyzed
      for open conversion rates, operative times, intra- and postoperative
      complications, and hospital stay. RESULTS: Of the 1,638 study patients 473
      (28.9%) had undergone previous abdominal surgery: 58 upper and 415 lower
      abdominal operations. The 262 patients who had undergone only a previous
      appendectomy were excluded from further analysis. Adhesions were found in 70.7%,
      58.8% and 2.1% of patients respectively, who had previous upper, lower or no
      previous abdominal surgery with adhesiolysis required, respectively, in 78%, 30%
      and 0% of these cases. There were no complications directly attributable to
      adhesiolysis. Patients with previous upper abdominal surgery had a longer
      operating time (66.4 +/- 34.2 min), a higher open conversion rate (19%), a higher
      incidence of postoperative wound infection (5.2%), and a longer postoperative
      stay (3.4 +/- 2.1 days) than those who had undergone previous lower abdominal
      surgery (50.8 +/- 24 min, 3.3%, 0.7%, and 2.6 +/- 1.4 days, respectively) and
      those without prior abdominal surgery (47.4 +/- 25.6 min, 5.4%, 1.2%, and 2.8 +/-
      1.9 days, respectively). CONCLUSIONS: Previous abdominal operations, even in the
      upper abdomen, are not a contraindication to safe laparoscopic cholecystectomy.
      However, previous upper abdominal surgery is associated with an increased need
      for adhesiolysis, a higher open conversion rate, a prolonged operating time, an
      increased incidence of postoperative wound infection, and a longer postoperative
      stay.

PMID- 14569456
TI  - Inter- and intraindividual variabilities of perforation forces of human and pig
      bowel tissue.
AB  - BACKGROUND: A laparoscopic bowel grasper should be suitable for safely grasping
      the bowel in a wide variety of patients. Therefore, the inter- and
      intraindividual variabilities in the strength of bowel tissue to resist
      perforation force should be analyzed. METHODS: The large and small bowels of pigs
      ( n = 14) and the human small bowel ( n = 7) were clamped between two hemispheres
      1.5 mm in diameter. The pinch force was increased until the tissue was
      perforated. RESULTS: The perforation force for the pig large bowel was higher
      than for the small bowel (13.5 +/- 3.7 vs 11.0 +/- 2.5 N; p = 0.014). No
      difference was found between the human and pig small bowel (10.3 +/- 2.9 vs 11.0
      +/- 2.5 N). The intercoefficient of variation varied between 22% and 28%, and the
      intracoefficient of variation varied between 14% and 18%. CONCLUSIONS: The
      strength of the pig bowel is approximately comparable to the strength of the
      human bowel, and, therefore, testing of graspers on pig bowel is justified.
      However, due to the large interindividual variation, large safety margins should
      be taken into account.

PMID- 14569457
TI  - Robot-assisted laparoscopic choledochojejunostomy.
AB  - BACKGROUND: Endoscopic stenting is the treatment of choice for palliative relief
      of biliary obstruction by a periampullary tumor. If treated surgically, a
      choledochojejunostomy and Roux-en-Y diversion is still performed by laparotomy in
      a large number of cases due to technical challenges of the biliodigestive
      anastomosis in the laparoscopic approach. Robotic systems may enhance dexterity
      and vision and might therefore support surgeons in delicate laparoscopic
      interventions. The purpose of this study is to assess the efficacy and safety of
      performing a laparoscopic choledochojejunostomy and Roux-en-Y reconstruction with
      the aid of a robotic system. METHODS: Ten laparoscopic procedures were performed
      in pigs with the da Vinci robotic system and compared to 10 procedures performed
      by laparotomy (controls). Operation room time, anastomoses time, blood loss, and
      complications were recorded. The effectiveness of the anastomoses was evaluated
      by postoperative observation for 14 days and by measuring passage, circumference,
      and number of stitches. RESULTS: Operating room time was significantly longer for
      the robot-assisted group than for controls (140 vs 82 min, p < 0.05). The
      anastomoses times were longer in the robot-assisted cases but not statistically
      significant (biliodigestive anastomosis, 29 vs 20 min; intestinal anastomosis, 30
      vs 15 min), Blood loss was less than 10 cc in all robot-assisted cases and 30 cc
      (10-50 cc) in the controls. In both groups, there were no intraoperative
      complications. In the control group, one pig died of gastroparesis on
      postoperative day 6. In the robot-assisted group, one pig died on postoperative
      day 7 due to a volvulus of the jejunum. At autopsy, a bilioma was found in one
      pig in the robot-assisted group. In all pigs, the biliodigestive and intestinal
      anastomoses were macroscopically patent with an adequate passage. Circumference
      and number of stitches were similar. CONCLUSION: The safety and efficacy of robot
      assisted laparoscopic choledochojejunostomy was proven in this study. The
      procedure can be performed within an acceptable time frame.

PMID- 14569458
TI  - Overexpression of TIMP-1 under the MMP-9 promoter interferes with wound healing
      in transgenic mice.
AB  - We have generated transgenic mice harboring the murine matrix metalloproteinase 9
      (MMP-9) promoter cloned in front of human TIMP-1 cDNA. The transgenic mice were
      viable and fertile and exhibited normal growth and general development. During
      wound healing the mice were shown to express human TIMP-1 in keratinocytes that
      normally express MMP-9. However, the healing of skin wounds was significantly
      retarded with slow migration of keratinocytes over the wound in transgenic mice.
      In situ zymography carried out on wound tissues revealed total blockage of
      gelatinolytic activity (i.e., MMP-9 and MMP-2). The results confirm studies with
      MMP-9 knockout mice showing that MMP-9 is not essential for general development,
      but they also demonstrate an important role of keratinocyte MMP-9, as well that
      of other keratinocyte MMPs that are inhibited by TIMP-1, in wound healing. The
      transgenic mice generated in this study provide a model for the role of MMPs in
      MMP-9-producing cells in other challenging situations such as bone fracture
      recovery and cancer invasion.

PMID- 14569459
TI  - De novo insertion of an Alu sequence in the coding region of the CLCN5 gene
      results in Dent's disease.
AB  - Dent's disease is an X-linked renal tubular disorder characterized by low
      molecular-weight proteinuria, hypercalciuria, nephrocalcinosis, nephrolithiasis,
      and eventual renal failure. Various types of mutations in the renal chloride
      channel gene, CLCN5, have been identified in patients with this disease. We
      studied a Spanish patient with Dent's disease and found, by polymerase chain
      reaction amplification of the CLCN5 exons, an abnormally large exon 11.
      Sequencing analysis revealed that this was attributable to the insertion in codon
      650 of an Alu element of the "young" Ya5 subfamily. The Alu element was inserted
      with the same orientation as the CLCN5 gene and arose de novo on the maternal
      chromosome. Polymorphism analysis indicated that the insertion occurred in the
      germline of the maternal grandfather. The presence of a long poly(A) tract and
      evidence for a 16-bp target-site duplication implied that the Alu element was
      integrated by retrotransposition. This mutation predicts a truncated ClC-5
      protein that lacks part of the carboxy-terminus and is likely to result in loss
      of function of the chloride channel. Insertions of Alu sequences, which are
      rarely found in coding regions, have occasionally been reported to cause other
      genetic diseases. However, this is the first report of a retrotransposon
      insertion in the CLCN5 gene associated with Dent's disease.

PMID- 14569460
TI  - Members of the CDY family have different expression patterns: CDY1 transcripts
      have the best correlation with complete spermatogenesis.
AB  - The CDY family of genes is of special interest because some of them are included
      in chromosome-Y microdeletions detected among infertile men and are apparently
      involved in the spermiogenetic process. In this study, we employed the reverse
      transcriptase/polymerase chain reaction technique to test the RNA expression of
      the various transcripts of these genes in testicular biopsies of 84 azoospermic
      men who had been classified by comprehensive histology and cytology analyses. We
      also evaluated the feasibility of detecting CDY expression in biopsies taken by
      testicular sperm extraction versus acquisition by aspiration. There was a
      significant association between the type of testicular impairment and the
      expression of CDY1 and CDY2 transcripts. CDY2 was expressed whenever germ cells
      were present, but CDY1 major and especially CDY1 minor and short transcripts were
      identified almost exclusively when mature spermatids/spermatozoa were detected.
      The expression of CDY1 minor and short transcripts detected in aspirated
      specimens was less efficient than that in testicular tissue acquired by
      extraction. It is suggested that CDY2 is apparently required in the early stages
      of spermatogenesis, whereas CDY1 transcripts are required later on in the
      process. The findings of this study imply different functional roles for CDY
      isoforms during spermatogenesis. However, in consideration of the high levels of
      identity between CDY1 and CDY2 (98% at the protein level), the delayed up
      regulation of CDY1 transcripts could be attributable to temporal changes in
      dosage requirements.

PMID- 14569461
TI  - Chromosomal phylogeny and evolution of gibbons (Hylobatidae).
AB  - Although human and gibbons are classified in the same primate superfamily
      (Hominoidae), their karyotypes differ by extensive chromosome reshuffling. To
      date, there is still limited understanding of the events that shaped extant
      gibbon karyotypes. Further, the phylogeny and evolution of the twelve or more
      extant gibbon species (lesser apes, Hylobatidae) is poorly understood, and
      conflicting phylogenies have been published. We present a comprehensive analysis
      of gibbon chromosome rearrangements and a phylogenetic reconstruction of the four
      recognized subgenera based on molecular cytogenetics data. We have used two
      different approaches to interpret our data: (1) a cladistic reconstruction based
      on the identification of ancestral versus derived chromosome forms observed in
      extant gibbon species; (2) an approach in which adjacent homologous segments that
      have been changed by translocations and intra-chromosomal rearrangements are
      treated as discrete characters in a parsimony analysis (PAUP). The orangutan
      serves as an "outgroup", since it has a karyotype that is supposed to be most
      similar to the ancestral form of all humans and apes. Both approaches place the
      subgenus Bunopithecus as the most basal group of the Hylobatidae, followed by
      Hylobates, with Symphalangus and Nomascus as the last to diverge. Since most
      chromosome rearrangements observed in gibbons are either ancestral to all four
      subgenera or specific for individual species and only a few common derived
      rearrangements at subsequent branching points have been recorded, all extant
      gibbons may have diverged within relatively short evolutionary time. In general,
      chromosomal rearrangements produce changes that should be considered as unique
      landmarks at the divergence nodes. Thus, molecular cytogenetics could be an
      important tool to elucidate phylogenies in other species in which speciation may
      have occurred over very short evolutionary time with not enough genetic (DNA
      sequence) and other biological divergence to be picked up.

PMID- 14569465
TI  - Comparison of health-related quality of life and prostate-associated symptoms
      after primary and salvage cryotherapy for prostate cancer.
AB  - PURPOSE: Recent advances in cryosurgery of the prostate have led to the ability
      to treat tumors successfully with decreased morbidity. The patients' perspectives
      of this relatively new technique, however, have not yet been addressed. The
      purpose of this study was to compare health related quality of life (QoL) as well
      as prostate-associated symptoms in patients after primary and salvage
      cryoablation for clinically localized prostate cancer using a self-administered
      questionnaire. METHODS: A total of 131 consecutive patients who underwent
      cryoablation of the prostate between 1997 and 2001 were included in this
      confidential mailing study. The patients were either (a) patients with localized
      prostate cancer with contraindications for radical surgery, including patients
      refusing other forms of therapy, or (b) had locally recurrent prostate cancer
      after failure of radiation therapy. All patients received 3 months of neoadjuvant
      androgen deprivation therapy prior to cryosurgery and were surgically treated by
      the same surgeon using an argon-based system. We used the EORTC QLQ-C30, a
      commonly used, multidimensional instrument together with a supplementing,
      prostate-cancer-specific module. RESULTS: Eighty-one of the 131 patients
      (response rate 62%) returned the questionnaires. The two groups were comparable
      regarding age (mean age 72.8 vs 70.1 for the primary and the salvage group,
      respectively; p=0.22). The overall QoL scores were high in both groups. Primary
      cryotherapy patients fared significantly better regarding physical (p=0.005) and
      social (p=0.024) functioning compared with salvage cryotherapy patients. The most
      prominent prostate-related symptom in both patient groups was sexual dysfunction,
      followed by urinary symptoms, which were significantly more severe in the salvage
      group (p=0.001). Incontinence rates were 5.9 and 10% in the primary and the
      salvage group, respectively. Severe erectile dysfunction was reported in 86 and
      90% of the primary and the salvage group, respectively. CONCLUSIONS: The present
      study demonstrates that, in selected patients, cryotherapy is a treatment option
      which has a functional outcome comparable to traditionally used prostate cancer
      treatments. More information regarding QoL is necessary for appropriate patient
      counseling and individual decision-making in the presence of various treatment
      alternatives.

PMID- 14569463
TI  - DNA sequence variation of the human ABO-secretor locus ( FUT2) in New Guinean
      populations: possible early human migration from Africa.
AB  - We have investigated the allelic polymorphism of the human ABO-secretor locus (
      FUT2) in 90 unrelated Papuan-speaking New Guineans (Dani group), 101 admixed New
      Guineans from Irian Jaya, Indonesia, and 32 New Guineans from Papua New Guinea by
      DNA sequencing analysis. Whereas the total frequency of various nonfunctional
      alleles at the FUT2 locus in the worldwide populations so far examined is around
      0.5, we have found only one individual heterozygous for a nonfunctional allele in
      the 90 Dani group members and a frequency of nonfunctional alleles of 0.1-0.2 in
      the admixed New Guineans. Admixed New Guineans had the Asian-specific null allele
      se(385) and the characteristic nonfunctional allele se(del2) found in
      Polynesians. In addition, both New Guinean populations had unique functional
      alleles ( Se(375) and Se(400)) with high frequencies (0.11-0.37); these are
      absent in other populations of the world except for African and Samoan
      populations. The Se(375) allele had G and C at positions 1009 and 1011 of the 3'
      untranslated region, respectively, whereas all other FUT2 alleles found so far in
      the world, except for se(428), have 1009A and 1011T. The Se(375) allele found in
      Africans has 1009G and 1011T, or 1009A and 1011T. Corresponding positions of
      nonhuman primates have G and C, suggesting that the Se(375) allele is one of the
      ancestral alleles, reflecting the early human migration from Africa to New Guinea
      and the long isolation of Dani populations from neighboring populations.

PMID- 14569467
TI  - [Editorial].

PMID- 14569466
TI  - Increased expression of MMP-2 and MMP-9 in esophageal squamous cell carcinoma.
AB  - PURPOSE: Matrix metalloproteinases (MMPs) are known to play an important role in
      extracellular matrix remodeling during the process of tumor invasion and
      metastasis. However, little is known about their role in preinvasive lesions and
      early esophageal carcinomas. METHOD: Immunohistochemical analysis of matrix
      metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) expression was
      carried out in paraffin-embedded sections of surgically resected esophageal
      squamous cell carcinoma (ESCC) (58 cases) and paired distal normal esophageal
      tissues (44 cases) and correlated with clinicopathological parameters. RESULT:
      Overexpression of MMP-2 and MMP-9 proteins was observed in 39 (67%) and 32 (55%)
      of the 58 ESCCs, respectively localized in tumor cell cytoplasm and stromal
      elements. Histological evaluation of hematoxylin- and eosin-stained 44 matched
      distal normal esophageal tissue sections revealed that 26 comprised of normal
      epithelium, while 15 tissues showed evidence of dysplasia and three tissues
      showed hyperplasia. Interestingly, 12 (80%) and 13 (87%) of these 15 dysplasias
      showed immunostaining for MMP-2 and MMP-9 proteins, respectively. Low levels of
      MMP-2 and MMP-9 were observed in 10 (38%) and 6 (23%) of 26 matched
      histologically normal esophageal tissues, respectively. Higher MMP-2
      immunopositivity was observed in well and moderately differentiated SCCs in
      comparison with poorly differentiated tumors. The expression of MMP-2 was
      significantly reduced with the progressive de-differentiation of esophageal SCCs
      ( P =0.03). Overexpression of MMP-2 and MMP-9 in dysplasia as well as SCC
      suggests that these alterations occur in early stages of esophageal
      tumorigenesis. CONCLUSION: Increased levels of MMP-2 and MMP-9 proteins in ESCCs
      as compared to normal esophageal tissues suggest their association with
      esophageal tumorigenesis. Increased levels of these MMPs are observed in majority
      of dysplasias analyzed herein, indicating that these alterations may be early
      events in esophageal tumorigenesis. In-depth studies are warranted to determine
      their role in development and progression of esophageal cancer.

PMID- 14569462
TI  - Evidence of linkage of HDL level variation to APOC3 in two samples with different
      ascertainment.
AB  - The APOA1-C3-A4-A5 gene complex encodes genes whose products are implicated in
      the metabolism of HDL and/or triglycerides. Although the relationship between
      polymorphisms in this gene cluster and dyslipidemias was first reported more than
      15 years ago, association and linkage results have remained inconclusive. This is
      due, in part, to the oligogenic and multivariate nature of dyslipidemic
      phenotypes. Therefore, we investigate evidence of linkage of APOC3 and HDL using
      two samples of dyslipidemic pedigrees: familial combined hyperlipidemia (FCHL)
      and isolated low-HDL (ILHDL). We used a strategy that deals with several
      difficulties inherent in the study of complex traits: by using a Bayesian Markov
      Chain Monte Carlo (MCMC) approach we allow for oligogenic trait models, as well
      as simultaneous incorporation of covariates, in the context of multipoint
      analysis. By using this approach on extended pedigrees we provide evidence of
      linkage of APOC3 and HDL level variation in two samples with different
      ascertainment. In addition to APOC3, we estimate that two to three genes, each
      with a substantial effect on total variance, are responsible for HDL variation in
      both data sets. We also provide evidence, using the FCHL data set, for a
      pleiotropic effect between HDL, HDL3 and triglycerides at the APOC3 locus.

PMID- 14569468
TI  - [The Boratav Depression Screening Scale (Bordepta): a sensitive scale for
      recognizing depression in epidemiologic studies and primary health care].
AB  - OBJECTIVE: To develop a sensitive scale able to recognize depression in
      epidemiological surveys and primary health care. METHOD: The research was
      designed as an initial preliminary investigation followed by two subgroup
      studies. The preliminary study involved the selection of queries that would
      constitute the scale, based on the rule of brief reply. The first sub-study was
      intended to test the reliability and validity of the developed scale in a group
      of patients previously diagnosed with depressive disorder (n=60) and/or
      generalized anxiety disorder (n=61). The second sub-study aimed to determine the
      sensitivity, specificity and appropriate cut-off points of the scale, based on
      results obtained from non-psychiatric patients (n=96) and normal subjects (n=7).
      RESULTS: Item analysis showed a significant correlation varying from 0.501 to
      0.729 between each item and total scale score. The Cronbach alpha value of the
      scale was 0.9005. Clinician-oriented vs. self report rating reliability
      correlation coefficient values were 0.534 to 0.850 (Kappa) and 0.856 (Pearson)
      for items and total scale score respectively. The concurrent validity of the
      scale as correlated with The Beck Depression Inventory and Trait Anxiety Scale
      were 0.812 and 0.763 respectively. The discriminant validity of items in terms of
      P values determined by chi-square testing was 0.021 to 0.0001. The sensitivity
      and specificity of the scale were 97.6% and 82% respectively at a cut-off point
      of 6.5, and 85.7% and 95.1% at 7.5. CONCLUSION: Boratav depression screening
      scale is valid and reliable, including optimal sensitivity and specificity for
      recognizing depression in epidemiologic studies and primary health care.

PMID- 14569469
TI  - [Relationship between blood glucose control and psychiatric disorders in type II
      diabetic patients].
AB  - OBJECTIVE: To explore specific psychiatric comorbidity among type II DM patients
      with poor and good glycemic control. METHOD: One hundred four patients with type
      II DM attending outpatient department of the Endocrinology Unit of Suleyman
      Demirel University Medical Faculty were included in this study. Patients were
      divided into two groups according to HbA1c level: >7% defined group 1 with poor
      glycemic control (n=40), and <7% defined group 2 with good glycemic control
      (n=64). All patients were assessed using a semi structured sociodemographic data
      form, the Structured Clinical Interview for DSM-IV-Clinical Version (SCID-I/CV),
      Hamilton Depression Rating Scale (HDRS), Hamilton Anxiety Rating Scale (HARS) and
      the Minimental State Examination Scale. RESULTS: The prevalence rate of
      psychiatric disorders were as follows: major depressive disorder 67.5%, dysthymic
      disorder 10.0%, generalized anxiety disorder 7.5%, obsessive compulsive disorder
      5%, social phobia 2.5% and nicotine dependence 5% in group 1 patients; and major
      depressive disorder 43.8%, dysthymic disorder 10.9%, paranoid disorder 3.1%,
      obsessive compulsive disorder 6.3%, social phobia 4.7%, generalized anxiety
      disorder 6.3%, nicotine dependence 9.4% and alcohol dependence 3.1% in group 2
      patients. Major depressive disorder frequency was significantly higher in group1
      patients than group 2 patients. HDRS and HARS scores were significantly higher in
      group 1 patients than in group 2 patients. Significant positive correlations were
      found between HDRS, HARS scores, number of depressive episodes and the level of
      HbA1c in the diabetic patients. CONCLUSION: Major depressive disorder was more
      frequent in diabetic patients with poor glycemic control than in those with good
      glycemic control. There was a strong association between level of HbA1c and
      depression and anxiety symptom level.

PMID- 14569470
TI  - [Multidimensional anger scale].
AB  - OBJECTIVE: To develop a new and original scale which can measure anger on a
      multidimensional level. METHOD: In the first phase of this study, 2 pilot studies
      were conducted. The first pilot study was conducted on a sample of 60 individuals
      to develop an item pool. A second pilot study was conducted with another group of
      148 individuals using a 429 item scale that was developed from this item pool.
      After the item analyses, a 158 item 'Multidimensional Anger Scale' (MAS) was
      derived for use in the second phase of the study to investigate the psychometric
      properties of the instrument. In the second phase reliability and validity
      analyses of this scale with 5 dimensions, Anger symptoms, Anger eliciting
      situations, Anger related cognitions, Anger reactions and Interpersonal Anger,
      were conducted on a sample of 756 individuals. RESULTS: Psychometric analysis of
      the scale showed that it possessed adequate internal consistency (alpha
      coefficients between 0,64 and 0,95). The validity of the scale was supported by
      the expected pattern of relations with other inventories (Brief Symptom Inventory
      and Guilt and Shame Scale). CONCLUSION: Multidimensional Anger Scale, for Turkish
      culture, may be suggested as a valid and reliable scale to measure anger in
      different dimensions.

PMID- 14569471
TI  - [Relatives' beliefs and attitudes towards schizophrenia: an epidemiological
      investigation].
AB  - OBJECTIVE: To examine relatives' beliefs and attitudes towards schizophrenia.
      METHOD: Data were derived from the demographic and schizophrenia modules of the
      questionnaire developed for the survey called "Attitudes Towards Mental
      Disorders". The questionnaire was administered 98 adult relatives of
      schizophrenic patients who had participated in psychiatric outpatient treatment
      programs in Istanbul, Izmir and Adana. RESULTS: Although all identified the case
      described as a mental disorder, only 76.5% determined the term schizophrenia as a
      mental disorder. Social problems (62.9%) and weakness of will (65.3%) were the
      most commonly endorsed causes of schizophrenia. Almost all of the respondents
      preferred medical methods and psychiatrists for the treatment of schizophrenic
      patients. 72.2% of the sample held the opinion that people with schizophrenia are
      dangerous and 91.8% believed that these patients could not take responsibility
      for their own lives. The attitudes of the subjects living in Istanbul and those
      who stated that "schizophrenia is an illness or a mental disorder" were more
      negative than the others with respect to social distance characteristics.
      CONCLUSION: Most of the relatives of schizophrenic patients identified a mental
      disorder when a schizophrenia case was described, but they had insufficient
      information about the term schizophrenia. Labeling patients as mentally ill had a
      negative effect on relatives' attitudes towards schizophrenia. The results of
      this study underlined the need for education programs for the relatives of
      patients, and the demands of the relatives concerning treatment modalities with
      psychosocial components.

PMID- 14569472
TI  - [Comorbidity of alcohol-substance use disorders in schizophrenia: a review].
AB  - There is a high alcohol/substance use disorder comorbidity rate in schizophrenia.
      This article reviews the prevalence of comorbid alcohol-substance use disorders
      in schizophrenia, methodological problems while examining this topic, etiological
      models, the impact of alcohol-substance use disorders on course and outcome of
      schizophrenia and treatment of these comorbid conditions. The literature search
      was conducted through the Medline records of the National Library of Medicine.
      The etiology of high prevalence rate of alcohol-substance use disorders in
      schizophrenia is unclear. There is support for the supersensitivity model which
      posits that biological vulnerability of psychiatric disorders results in
      sensitivity to small amounts of alcohol and drugs, leading to substance use
      disorders. There is minimal support for the self-medication model, but the
      accumulation of other risk factors, may increase the risk of substance use
      disorder. While planning the risk prevention, care and treatment of schizophrenic
      patients, alcohol-substance abuse must also be evaluated. Particularly young male
      patients, patients who have antisocial personality properties and depressive
      symptoms must be taken as a group with risk and alcohol-substance use must be
      evaluated carefully in this population. Relapses, violence and suicide risks must
      be taken in to account while treatment of these comorbid patients. They must be
      taken as a different group regarding the treatment and some special interventions
      must be taken with these patients.

PMID- 14569473
TI  - [Structural magnetic resonance imaging (MRI) studies in bipolar disorder].
AB  - To review structural MRI studies in bipolar disorder. A computer-assisted
      literature search of the Medline Ovid files for the period 1966 to November 2002
      was performed, augmented by the use of articles meeting the criteria of this
      study from recent reviews. The studies included in this review show that there
      are abnormalities in the regions playing a role in the prefrontal-subcortical
      circuits that have been implicated in the pathophysiology of bipolar disorder,
      rather than generalized abnormalities like cerebral volume reduction or
      ventricular enlargement. The most widely studied and frequently reported finding
      of T2 signal hyperintensities is not considered to be specific to bipolar
      disorder. The findings of dorsolateral and subgenual prefrontal cortical
      volumetric reductions are in agreement with the findings of few neuropathological
      studies of bipolar disorder and suggest that prefrontal cortex plays an important
      role in the pathophysiology of the disorder. Among the medial temporal
      structures, the increase in amygdala volume seems to be specific to bipolar
      disorder. The findings in structures like the striatum and thalamus are
      conflicting, due to difficulties in the detailed measuring of the volumes of
      these structures with current techniques. Bipolar disorder is associated with
      brain abnormalities detected with structural MRI. Studies integrating structural
      neuroimaging methods with functional neuroimaging are needed to specifically
      determine how these abnormalities affect the function of these brain regions.

PMID- 14569474
TI  - [Forty-six year old baby].
AB  - In this paper, an extraordinary mother-son relationship involving 46 year-old,
      married, male patient with three children is discussed. He had never had any
      psychiatric complaint until his mother's death. However, he developed severe
      depressive and somatic symptoms following his 80 year-old mother's death. He
      showed no significant improvement after previous outpatient treatments and was
      admitted to the Psychiatric Department of Ege University School of Medicine with
      complaints of tension, insomnia, fatigue, anhedonia, hopelessness and pain all
      over his body. It was discovered that this man, who was loved and respected by
      both his family and his peers, used to suck his mother's breast twice daily. This
      act was no secret and was not considered a reason for seeking psychiatric help, a
      symptom of a disorder, or a source of distress for the son, mother, or any other
      family member. A phenomenon like this has never been reported in the literature
      before. We discuss this phenomenon through the dynamic formulation of the case
      using data from his psychiatric and developmental history as well as direct
      observation and psychological tests.

PMID- 14569475
TI  - [A case report of factitious disorder with hallucinations].
AB  - Although factitious disorder has been known for a long time, its diagnosis and
      treatment continue to be a problem. It is an uncommon condition associated with
      considerable morbidity and health care expenditure. We present a case of
      factitious disorder with hallucinations. A 37 year-old single woman has had
      auditory and olfactory hallucinations for six years. She had been diagnosed with
      schizophrenia, hospitalized for a short term, taking classical antipsychotic
      drugs for years. She has been performing her job as a teacher and living with her
      family. A suitable dose of atypical antipsychotic drugs was administered at a
      convenient time for her illness (Psychotic Disorder NOS) in psychiatric
      outpatient clinic of Kocaeli University. She was admitted to inpatient clinic
      twice in order to allow a clear diagnosis to be made. Psychotic disorder and
      temporal lobe epilepsy were ruled out. Borderline and histrionic personality
      traits were determined. Her complaints were unchanged over the course of
      treatment taking three years. She later started to come into the emergency
      department with anxiety symptoms, conversion like fits and suicide attempts;
      hospitalized for these complaints in another hospital. She was diagnosed with
      factitious disorder because of her unchanged complaints, her adding new
      complaints to the old ones, her complaints unrelated to psychosocial stressors,
      her ambitions to come to hospital, her increasing hospital dependence and having
      no prominent secondary gain. This case emphasizes the need for the careful
      observation of patients to prevent unnecessary investigations at the diagnosis
      and treatment stage and to establish a specific management strategy for the
      patients.

PMID- 14569476
TI  - [Role of the surgeon in the hospital infections control committees].
AB  - Hospital-acquired infections are the ones that develop within hospital stay or
      appear after discharge. These infections are associated with an increased rate of
      morbidity and mortality, longer hospital stay and higher hospital costs and
      Hospital Infections Control Committees have been founded to prevent it. In this
      review, we intended to investigate the role of the surgeon in this committee.

PMID- 14569477
TI  - Effects of hepatectomy and arginine enriched diet on colonic mucosa originated
      inflammatory cytokines.
AB  - AIM: To assess the effects of arginine-enriched diet and partial hepatectomy in
      rats on gut-originated inflammatory cytokines. METHODS: Of 24 rats, Group 1 and 2
      animals were fasted 24 hours before surgery, Group 3 and 4 animals received
      regular plus arginine-enriched diet(AED). Group 2 and 4 animals had undergone 30%
      hepatic resection. Leukotriene B4 (LT B4) levels were detected in colonic mucosa
      and mucosal perfusates immediately after resection. Mean leukocyte counts (MLC)
      were detected also in the mucosa. RESULTS: In the basis of fasting situation
      regardless hepatectomy, all MLC were lower in Group 3 and 4 but LTB4 levels both
      in mucosa and perfusate were higher. On hepatectomy based comparison there was
      not any statistically significant difference between groups but mucosal perfusate
      LTB4 levels. But when hepatectomy added on fasted animals MLC levels were lower
      than fed by AED + sham operation. LTB4 levels were insignificant in both
      perfusate and mucosa. When hepatectomy added on AED animals (Group 4), MLC
      decreased and mucosal LTB4 increased when they compared with fast without
      hepatectomy Group 1. CONCLUSIONS: AED prior to extra-intestinal operations may
      trigger inflammatory cascade and complications via leucocyte degradation and
      LTB4.

PMID- 14569478
TI  - [The effects of lactated ringer's resuscitation on tissue blood flows and oxidant
      injury in experimental crush injury in rats].
AB  - BACKGROUND: In an experimental model of crush injury, tissue blood flow, the
      extend of oxidant injury and the effect of lactated ringer's resuscitation were
      investigated. MATERIAL AND METHOD: Rats were divided into sham (n: 8), crush
      injury (n: 8), and crush injury + lactated ringer's resuscitation (n: 8) groups.
      Arterial and venous catheterization were performed in all groups. Crush injury
      was done with intravenous infusion of allogenic muscle extract. In the crush
      injury + lactated ringer's resuscitation group 30 ml/kg lactated ringer's
      solution was infused in 30 minutes. Kidney and liver blood flow were measured by
      using a laser flowmeter. To assess the oxidant injury blood, liver, and kidney
      tissue samples were collected for malondialdehyde and glutathione measurements.
      RESULTS: In the crush injury, diminished liver and kidney blood flow rates were
      improved with lactated ringer's resuscitation. In addition, glutathione levels
      decreased whereas malondialdehyde levels and base deficit increased. Lactated
      ringer's resuscitation brought base deficit to the control levels. When compared
      with the crush injury, lactated ringer's infusion increased the glutathione
      levels but could not decrease the malondialdehyde ones. CONCLUSION: Lactated
      ringer's resuscitation improved the blood flow rates but could not prevent
      oxidant injury totally.

PMID- 14569479
TI  - [Complicated Meckel's diverticulum].
AB  - BACKGROUND: In this study we present our experience in the surgical treatment of
      complicated Meckel's diverticulum. METHODS: The data of eight patients who
      underwent surgery due to complications of Meckel's diverticulum between 1994-2001
      was retrospectively assessed. RESULTS: There were six males and two females with
      a mean age of 31 years (range 13 to 65). Preoperative diagnoses were acute
      surgical abdomen in six and incarcerated inguinal hernias in two patients.
      Intraoperative diagnoses were as follows; Littre's hernia in two, diverticulitis
      in two, perforation of the diverticulum in one and intestinal obstruction in
      three patients (there was a band extending from diverticulum to the umbilicus in
      two patients and a mesodiverticular band in the remaining one). While
      diverticulectomies were performed in five patients, three had small bowel
      resections. The mean diameter of the diverticula was 2.3 cm (range 2 to 4) and
      the mean length was 3.5 cm (range 3 to 8). Postoperative intestinal obstruction
      was observed in one patient who had underwent diverticulectomy and subsequently a
      small bowel resection was performed. CONCLUSION: Being aware of the complications
      of the Meckel's diverticulum is necessary in correct timing of the surgery and
      selecting the proper incision in patients with acute abdomen. This will result in
      decreased morbidity.

PMID- 14569480
TI  - The evaluation of the patients admitted to a burn center in Turkey.
AB  - BACKGROUND: Burns constitute an important part of the accident-related deaths due
      to high morbidity and mortality. METHODS: The medical records of 778 (279 female)
      patients who were treated during last three years period were retrospectively
      analyzed concerning age, gender, the cause of the burn, the month when the burn
      occurred, admission date, duration of the hospital stay, area of the burn. The
      relationship between these parameters and the mortality was analyzed. RESULTS:
      The average age of the patients was 20 years. The burns were related to accidents
      in 87% patients, abuse in 8%, co-morbid diseases in 3% and suicidal attempts in
      2%. In 48% of the cases there were hot fluid burns and in 37% (284) fire-flames.
      The burns were due to electrical burns in 13% patients and to other reasons in
      the remaining 2%. One hundred and seventy - two patients had fatal courses. The
      mortality rate was 75% in 12 patients who were above 60 years. Average burn area
      was 24% (10-100) and average hospital stay was 13 days. CONCLUSION: As most of
      the burns were due to accidents, the number of burns might be reduced by
      prioritizing preventive measures and better results could be obtained when the
      quality and the number of the burn centers is increased.

PMID- 14569481
TI  - Evaluation of physical findings in acute wrist trauma in the emergency
      department.
AB  - OBJECTIVE: The aim of the study was to evaluate the value of physical findings to
      predict fracture in patients with acute wrist trauma. METHODS: This prospective
      clinical study was conducted over a period of four months from December 1998. The
      patients who were older than 18 years and presenting with acute wrist trauma
      within 24 hours of the time of injury were included in the study. Magnetic
      resonance imaging (MRI) was done for the patients who had inconsistency between
      clinical and radiographic diagnosis. RESULTS: Fifty-five patients were included
      in the study. Four fractures were diagnosed on the MRI of eight patients who have
      contradiction between clinical diagnosis and X-ray studies. The positive
      predictive values of edema, localized tenderness, pain on active and passive
      motion, pain with grip and pain in supination were found as 95.2%, 67.3%, 77.3%,
      91,7%, 89.3%, and 96%, respectively. Physical findings having high sensitivity
      were found as localized tenderness (94.3%), pain on the active and passive motion
      (97.1%, 94.3%, respectively). Pain on the active and passive motion were
      determined as physical findings with highest negative predictive values (%90.9,
      %89.5, respectively). CONCLUSION: Edema, pain on grip and supination, and
      especially pain on passive and active motion and localized tenderness can be
      valuable to predict or rule out fracture in acute wrist trauma cases who have no
      deformity.

PMID- 14569482
TI  - Tracheobronchial foreign bodies: a 10 year experience.
AB  - BACKGROUND: Our aim is to describe foreign body aspiration in the
      tracheobronchial tree, a common emergency with serious consequences. METHODS: We
      reviewed the records of 357 patients who were admitted to our hospital during a
      10-year period for the treatment of aspirated foreign body into the
      tracheobronchial tree. RESULTS: Of these cases, 42.4% were male and 57.6% female.
      Their ages ranged from 4 months to 70 years (average of 10.8 years). The most
      common manifestation was coughing, with subsequent dyspnea and wheezing. All
      underwent rigid bronchoscopy for the removal of the foreign body. Foreign bodies
      were localized in the right bronchial tree in 188 cases (52.7%), the left in 107
      cases (30%) and trachea in 39 cases (10.9%). Foreign bodies were not found during
      bronchoscopy in 23 cases (6.4%). The foreign bodies were: needles (n=125),
      peanuts (n=110), plastic objects (n=52), and miscellaneous (n=47). Foreign bodies
      were removed by bronchoscopy in all but six cases (1.7%), who underwent limited
      thoracotomy. The present series had a mortality of 0.56 percent (two deaths)
      following removal of foreign body. CONCLUSIONS: Foreign body aspiration are
      rapidly recognized from the patient's history and easily treated by bronchoscopy
      and extraction of the aspirated foreign body. A high index of suspicion is
      crucial for early diagnosis. However, education is the best preventive measure
      for decreasing the incidence of this matter.

PMID- 14569483
TI  - [Clinical results of four hundred and twenty-four cases with chest trauma].
AB  - BACKGROUND: In this retrospective study, we aimed to emphasize that thoracentesis
      is a fast and safe method to evaluate indication for thoracotomy in patients with
      thoracic trauma who have preshock or shock findings, without losing time by other
      examinations such as X - ray studies. METHODS: File records of 424 patients who
      were admitted to Thoracic Surgery Deparments of Adiyaman State Hospital and
      Medical School of Yuzuncu Yil University between December 1994 and March 2002,
      were investigated. RESULTS: There were 371(87,5%) male and 53 (12,5%) female
      patients, aged 5 to 89 (mean, 38,35). Most of the patients (n:382, 90%) were
      recovered by tube drainage and conservative management. There were 30 (7.1%)
      cases who underwent thoracotomy or median sternotomy. Nine patients underwent
      thoracotomy after being diagnosed by only thoracentesis without X - ray and 8
      (89,9%) of them survived. The overall mortality was 2,8% (12 cases). CONCLUSION:
      Diagnostic thoracentesis has to be one of the indications for emergency
      thoracotomy after prompt systemic physical examination in the approach to
      thoracic trauma patient.

PMID- 14569484
TI  - [Chest trauma: analysis of 592 cases].
AB  - INTRODUCTION: Thoracic traumas constitute an important part of the patients who
      are being admitted to the emergency units and deaths due to trauma. The aim of
      this study was to compare our clinical experience and results of the literature.
      METHODS: 592 patients with thoracic trauma who were admitted to our clinic
      between 1996 and 2000 were evaluated retrospectively. RESULTS: 449 patients
      (75.8%) had blunt and 43 patients (24.2%) had penetrating thorax trauma. There
      was rib fracture in 448 patients (75.7%), clavicula fracture in 55 (9.2%),
      scapula fracture in 31 (5.2%) and sternal fracture in 20 (3.4%). In addition,
      flail chest was detected in 79 cases (13.3%). The most frequent complications
      were pneumothorax (n: 158; 26.7%), and hemothorax ( n: 119; 20.1% ). Three
      hundred and thirty - nine patients (57.2%) were treated by tube thoracostomy and
      190 by conservative management (32.1%). Surgical treatment was performed in 99
      (16.7%) patients. Morbidity was 18.4% ( n: 109 ) and mortality, 6.4% ( n: 38 ).
      Mean hospital stay time was 13.4 days (2 - 93 days). CONCLUSION: Thoracic traumas
      can cause vital organ injuries and impaired cardio-respiratory hemodynamics
      should be treated immediately.

PMID- 14569485
TI  - [Tracheobronchial injuries].
AB  - BACKGROUND: Tracheobronchial injuries are among the least common sort of thoracic
      traumas. This injury can be life threatening. However, successful diagnosis and
      treatment can prevent devastating acute or delayed complications. The aim of this
      study was to review the authors' surgical experience in tracheobronchial
      injuries. METHODS: We reviewed our records of 29 patients with tracheobronchial
      injuries from January 1979 to December 2000. The median age was 22.7. Twenty
      seven patients were male and two were females. RESULTS: The causes of traumas
      were penetrating injury in seventeen, blunt injury in eleven patients and animal
      bite in one. In sixteen patients cervical trachea, in nine main stem bronchus, in
      3 lobar bronchus and in one patient mediastinal trachea were found to be injured.
      In seven of twenty-nine patients there were combined tracheal and esophageal
      injuries. Surgical approach was made by oblique incision, collar incisions and
      thoracotomy. In general we preferred primary repair. The overall mortality rate
      was 24%. CONCLUSION: In our opinion, the number of complications and mortality
      can be diminished by early recognition of the injuries and treatment.

PMID- 14569486
TI  - [Diaphragmatic rupture in abdominal trauma].
AB  - BACKGROUND: The aim of the study is to evaluate the patients with diaphragmatic
      rupture due to penetrating or blunt abdominal trauma. METHODS: Thirty-eight
      patients with diaphragmatic rupture due to penetrating or blunt abdominal trauma
      were investigated retrospectively. RESULTS: The average age was 41,72 and there
      were 31 male and seven female patients. The injury forms were penetrating trauma
      in 22 (58%) and blunt trauma in 16 (42%) cases. Associated abdominal organ
      injuries were found in 27 (71%) cases. Among 47 diaphragmatic ruptures, 27 (57%)
      were on the left and 20 (43%) were on the right side. The average diameter of the
      rupture was 5,45 (1-20) cm. Management of the diaphragmatic rupture and other
      associated organ injuries were accomplished through laparotomy. Morbidity was
      developed in 18 cases and mortality in four cases with associated abdominal organ
      injuries. CONCLUSION: Diaphragmatic rupture results in high morbidity and
      mortality due to associated organ injuries.

PMID- 14569487
TI  - [Iatrogenic hypernatremia during hydatid cyst operation].
AB  - Hypernatremia due to salt gain is generally iatrogenic. This case report presents
      a 55 year-old woman who was operated because of hepatic hydatid cyst. At the end
      of the operation, following extubation the patient was unconscious and serum
      sodium concentration was found to be 185 mEq/ L. The patient was entubated again
      and transferred to the intensive care unit. When the patient awaked and became
      conscious at 36th hour in intensive care unit, she was extubated and transferred
      to ward with serum sodium concentration of 142 mEq/L. The serum sodium
      concentration should be monitored carefully in hydatid cyst operation, during
      which hypertonic saline is used for scelosidal effects as general anesthesia can
      mask neurologic signs due to hypernatremia.

PMID- 14569488
TI  - [Rupture of operated celiac artery aneurysm].
AB  - Celiac artery aneurysm is a rare and its rupture is the most frequent and serious
      complication. The patient who underwent aneurysmectomy and aorto - celiac artery
      synthetic prosthesis graft interposition in another cardiovascular surgery center
      two years ago, was admitted to our department with complaints of fever and
      abdominal discomfort. Computed tomography revealed an aneurysm with 1 cm of
      diameter at the beginning of celiac artery and intraperitoneal hemorrhage. Acute
      hematocrit descent was occurred and then cardiac arrest was taken place. So,
      emergency thoracotomy was done. Aorta was compressed with hand and at the same
      time internal cardiac resuscitation was done then cross clamp was placed onto
      aorta. Median abdominal incision was done and ruptured celiac artery aneurysm was
      observed. Infected graft was removed and PTFE graft was interposed from
      descending aorta to a. hepatica propria, away from the infected area. During 17
      months of follow-up period graft no complication was observed. We believe that
      because of its rarity, tendency to be asymptomatic along with high incidence of
      rupture, celiac artery aneurysms should not be underestimated.

PMID- 14569489
TI  - [Colorectal perforation due to self administered retrograde enema].
AB  - Retrograde irrigation enemas are commonly used in the treatment of chronic
      constipation especially in the elderly. We report a case of colorectal
      perforation due to self-administered retrograde water enema. A 55 year-old
      chronically constipated male patient was admitted to the emergency unit with
      severe diffuse abdominal pain. He administered rectal enema using a garden hose
      directly connected to the water two hours before admission, until he felt a
      sudden sharp abdominal pain. At the operation he was found to have a perforation
      along the antimesenteric border of distal sigmoid colon extending to the upper
      rectum. Primary resection and anastomosis with intraoperative colonic lavage was
      performed. Postoperative course was favorable without any wound infection or
      intraabdominal sepsis.

PMID- 14569490
TI  - [Color flow duplex ultrasonography is an effective alternative method].
AB  - Increasing use of percutaneous interventional cardiac and peripheral arterial
      procedures has resulted in high incidence of femoral pseudoaneurysms. This case
      report presents a 68 year-old male with a femoral pseudoaneurysms after
      percutaneous iliac transluminal angioplasty, who was treated with ultrasound
      guided compression successfully. Although surgical procedures are widely
      performed in Turkey, it should be kept in mind that compression therapy is
      effective and may present as an initial step in the management of femoral
      pseudoaneurysms.

PMID- 14569491
TI  - Tension pneumopericardium in chest trauma with gunshot wound.
AB  - Tension pneumopericardium is a rare complication of gunshot wounds. A 28 year-old
      male patient with tension pneumopericardium after chest trauma by gunshot bullet
      injury was reported. On initial examination, hemopneumothorax and fracture of the
      clavicle were found on the right side. Interestingly, there was no image of
      additional pneumopericardium on telecardiogram at the admission to the hospital.
      Following right tube thoracostomy, 900 ml of blood and some air were drained. Due
      to additional 400 ml blood drainage on the second day, right thoracotomy was
      performed. Laceration of the right lung and the bleeding from the right
      innominate vein were sutured. There was no visible pathology on pericardium.
      Tension pneumopericardium occurred on the second day of admission and a tube was
      inserted in to the pericardial space through subxyphoid incision. No blood but
      some air was drained from pericardial space. After removing the pericardial and
      right thorax tubes on the fifth and sixth days respectively, the patient was
      discharged with complete recovery.

PMID- 14569492
TI  - The biopersistence of Canadian chrysotile asbestos following inhalation.
AB  - Chrysotile asbestos is often included with other asbestos materials in evaluation
      and classification. However, chrysotile is a serpentine with markedly different
      physical and chemical characteristics in comparison to amphiboles (e.g.,
      crocidolite, amosite, tremolite). In contrast to amphiboles, which are solid,
      rodlike fibers, chrysotile is composed like a rope of many fine fibrils, which
      tend to unwind. In order to quantify the dynamics and rate by which chrysotile is
      removed from the lung, the biopersistence of a sample of commercial chrysotile
      from the Eastern Townships area of Quebec, Canada, labeled QS Grade 3-F, which is
      the longest commercial grade intended for textile use, was studied. As the long
      fibers have been shown to have the greatest potential for pathogenicity, the
      chrysotile samples were specifically chosen to have more than 200 fibers/cm3
      longer than 20 micro m present in the exposure aerosol. This publication presents
      the results of this study through 3 mo postexposure. The study design included:
      (1) Fiber clearance (lung digestions): At 1 day, 2 days, 7 days, 14 days, 1 mo, 3
      mo, and 12 mo (to be reported) following a 5-day (6 h/day) inhalation exposure,
      the lungs from groups of animals were digested by low-temperature plasma ashing
      and subsequently analyzed by transmission electron microscopy for total
      chrysotile fibers number in the lungs and chrysotile fiber size (length and
      diameter) distribution in the lungs. (2) Fiber distribution (confocal
      microscopy): This procedure was included in order to identify the location of the
      fibers in the lung. At 1 day, 2 days, 7 days, 14 days, 1 month, and 3 months (to
      be reported) postexposure, the lungs from groups of animals were analyzed by
      confocal microscopy to determine the anatomic fate, orientation, and distribution
      of the retained chrysotile fibrils deposited on airways and in the parenchymal
      region. Chrysotile was found to be rapidly removed from the lung. Fibers longer
      than 20 micro m were cleared with T(1/2) = 16 days, most likely by dissolution
      and disintegration into shorter fibers. The shorter fibers were also rapidly
      cleared from the lung, with fibers 5-20 micro m clearing even faster (T(1/2) =
      29.4 days) than those <5 micro m in length. The fibers <5 micro m in length
      cleared at a rate (T(1/2) = 107 days) that is within the range of clearance for
      insoluble nuisance dusts. The breaking apart of the longer fibers would be
      expected to increase the short fiber pool and therefore could account for this
      difference in clearance rates. The short fibers were not found clumped together
      but appeared as separate, fine fibrils, occasionally unwound at one end. Short
      free fibers appeared in the corners of alveolar septa, and fibers or their
      fragments were found within alveolar macrophages. The same was true of fibers in
      lymphatics, as they appeared free or within phagocytic lymphocytes. Neutrophil
      mediated inflammatory response did not occur in the presence of chrysotile fibers
      at the time points examined. Taken in context with the scientific literature to
      date, this report provides new robust data that clearly support the difference
      seen epidemiologically between chrysotile and amphibole asbestos.

PMID- 14569493
TI  - Comparative cytotoxicity study of rock wool and chrysotile by cell magnetometric
      evaluation.
AB  - Rock wool (RW), a type of man-made mineral fiber (MMMF), is a building material
      used as an asbestos substitute for heat insulation, fire resistance, and
      reinforcement. RW is included in group 3 of the IARC classification. In the
      present study, the cytotoxicity of RW was investigated by cell magnetometry,
      enzyme assay, DNA ladder detection, and electron microscopic morphological
      evaluation in comparison with chrysotile fibers (CF). Specimens were prepared by
      18-h incubation of Fischer rat alveolar macrophages in the presence of RW fibers
      as the study material, CF as positive control, and phosphate-buffered saline
      (PBS) as negative control, together with a relaxation indicator, Fe3O4, except
      for morphological evaluation, followed by additional procedures of external
      magnetization and subsequent 20-min remanent magnetic field measurement for
      magnetometric evaluation, and macrophage DNA extraction for evaluating possible
      apoptosis by DNA ladder detection. In magnetometry, relaxation, a marker of
      cytotoxicity, was rapid in both the RW- and PBS-treated groups, while it was
      delayed in both the long and short CF-treated groups. Differences in percent
      lactate dehydrogenase (LDH) release between the RW-treated group and PBS-treated
      group were not significant, but those between the RW-treated group and short CF
      treated group were statistically significant. A DNA ladder was not detected in
      any of the study groups. Electron micrographs showed that RW did not cause any
      change, but CF caused changes in macrophages. Thus, magnetometric measurements
      suggested no cytotoxicity of RW. We plan, in the future, to evaluate the safety
      of RW by magnetometric measurement and morphological observation of the lungs in
      in vivo inhalation experiments.

PMID- 14569494
TI  - Association between ozone and respiratory admissions among children and the
      elderly in Vancouver, Canada.
AB  - In this study, we examine the impact of ozone on daily respiratory admissions in
      both young children and the elderly in greater Vancouver, British Columbia. Study
      subjects included children less than 3 yr of age and adults 65 yr of age or over
      living in greater Vancouver who had acute hospital admissions for any respiratory
      diseases (ICD-9 codes 460-519) during the 13-yr period 1986-1998. Bidirectional
      case-crossover analysis was used to investigate associations between ambient
      ozone and respiratory hospitalizations after adjustment for other pollutants,
      including carbon monoxide, nitrogen dioxide, sulfur dioxide, and coefficient of
      haze. Potential effect modification by socioeconomic status as measured by
      household income was also examined. Respiratory admissions were associated with
      ozone levels 2, 3, 4, and 5 days prior to admission in both children and the
      elderly, with the strongest association observed at a lag of 4 days. Odds ratios
      for hospital admission of 1.22 (95% CI: 1.15-1.30) for children and 1.13 (1.09
      1.18) for the elderly, respectively, were found, based on an increment in
      exposure corresponding to the interquartile range for ozone. Adjusting for other
      pollutants did not attenuate the ozone effect on respiratory admissions. Nor did
      socioeconomic status appear to modify the association between ozone and
      respiratory admissions in either children or the elderly. We concluded that
      ambient ozone is positively associated with respiratory hospital admission among
      young children and the elderly in Vancouver, British Columbia. These associations
      persisted after adjustment for both copollutant exposures and socioeconomic
      status.

PMID- 14569496
TI  - Oxidative stress mediates air pollution particle-induced acute lung injury and
      molecular pathology.
AB  - Insight into the mechanism(s) by which ambient air particulate matter (PM)
      mediates adverse health effects is needed to provide biological plausibility to
      epidemiological studies demonstrating associations between PM exposure and
      increased morbidity and mortality. Although in vitro PM studies provide an
      understanding of mechanisms by which PM affects pulmonary cells, it is difficult
      to extrapolate from in vitro to in vivo mechanisms of PM-induced lung injury. We
      examined in vivo mechanisms of lung injury generated by oil combustion particles.
      Rats were pretreated with dimethylthiourea (DMTU) before intratracheal
      instillation of residual oil fly ash (ROFA). Animals were examined by
      bronchoalveolar lavage for biomarkers of lung injury, and lung tissues were
      examined by immunohistochemical, biochemical, and molecular approaches to
      identify ROFA-induced alterations in intracellular signaling pathways and
      proinflammatory gene expression. Significant increases in pulmonary inflammation,
      cytotoxicity, activation of ERK mitogen-activated protein kinase (MAPK), and
      increases in mRNA levels encoding macrophage inflammatory protein (MIP)-2,
      interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, MCP-1 and matrilysin were
      observed. DMTU pretreatment inhibited ROFA-induced pulmonary inflammation,
      cytotoxicity, ERK MAPK activation, and cytokine gene expression. Our findings
      provide coherence with in vitro PM mechanistic information, allow direct in vitro
      to in vivo extrapolation, and demonstrate a critical role for oxidative stress in
      ROFA-induced lung injury and associated molecular pathology.

PMID- 14569495
TI  - Optimization of route of administration for coexposure to ovalbumin and particle
      matter to induce adjuvant activity in respiratory allergy in the mouse.
AB  - Epidemiological and experimental studies have not only shown that air pollution
      induces increased pulmonary morbidity, and mortality, but also that air pollution
      components may potentiate allergic responses. The respiratory allergy model to
      ovalbumin in the mouse has been shown a useful tool to characterize the adjuvant
      potency of air pollution components. However, the choice for the most effective
      route of administration for testing small amounts of air pollution component is
      hampered by the diversity of routes of administration used. To test the adjuvant
      activity of airborne particles (Ottawa dust EHC-93), we studied the optimal route
      of respiratory administration: intranasally (in) and aerosol (aero) in comparison
      with responses observed by intraperitoneal (ip) with diesel exhaust particles
      (DEP) as a positive control. Our results show that the combination of in/aero
      with ovalbumin caused almost similar immunoglobulin (Ig)E and inflammatory
      responses compared to the ip/aero. In/in application induced less responses for
      IgE, less inflammation in the lung, and less increased numbers of eosinophils in
      the bronchoalveolar lavage (BAL). This response increased dramatically when
      ovalbumin was coadministered with DEP. Subsequently, EHC-93, which is made up of
      airborne particles, was tested via the in/in route of administration. EHC-93
      induced similar IgE responses, inflammation, and eosinophilic response in BAL
      compared to DEP. In addition, EHC-93 increased the airway responsiveness of the
      ovalbumin-sensitized mice measured in unrestrained condition and not in
      nonsensitized control mice. It is concluded that intranasal sensitization with
      intranasal challenge with airborne particles (EHC-93) is an effective route of
      administration to show potency of adjuvant activity of airborne particles.

PMID- 14569497
TI  - Effect of asphalt fume inhalation exposure at simulated road paving conditions
      prior to bacterial infection on lung defense responses in rats.
AB  - Asphalt fume inhalation has been suspected of affecting immune function in
      exposed workers. The objective of this study was to evaluate the effect of
      asphalt exposure on lung immune responses in rats using a bacterial infectivity
      model. Pathogen-free male Sprague-Dawley rats were exposed by inhalation to
      asphalt fumes (72.6 +/- 4.95 mg/m3) or filtered air for 6 h/day for 5 days. One
      day after the final asphalt exposure, rats were intratracheally inoculated with 5
      x 10(5) Listeria monocytogenes. At 0 (prior to bacterial inoculation), 3, and 7
      days after L. monocytogenes instillation, the lungs of each animal were divided.
      Bronchoalveolar lavage (BAL) was performed on right lungs. The recovered BAL
      cells were then differentiated and counted, and alveolar macrophage (AM) function
      was determined. Albumin and lactate dehydrogenase (LDH), two indices of lung
      injury, were measured in the acellular BAL fluid. To assess bacterial clearance,
      the left lungs were removed, homogenized, and bacterial colony-forming units
      (CFUs) were counted. In addition, lung-draining lymph nodes were removed, and
      lymphocyte phenotype and lymphocyte-induced cytokine production were examined.
      Asphalt fume exposure did not cause lung injury or inflammation in rats in the
      absence of infection. Infection induced elevations in AMs, neutrophils (PMNs),
      albumin, and LDH. Importantly, no significant differences were seen when
      comparing the asphalt group with the air and nonexposed naive groups at any time
      before or after infection. Also, asphalt fume inhalation exposure did not affect
      the rate of pulmonary clearance of L. monocytogenes or AM production of reactive
      oxygen and nitrogen species. However, asphalt-related increases in lymphocyte
      secretion of interferon (IFN)-gamma, interleukin (IL)-6, and IL-10 were observed
      at different times after bacterial infection, whereas the total number of lymph
      node cells and the percentage of CD4+ and CD8+ cells were not significantly
      different among the treatment groups. Despite the asphalt-induced changes
      observed in lymphokine secretion, adaptive immune function seemed to function
      properly in lung defense against bacterial infection. Because innate nonspecific
      lung responses and pulmonary clearance of L. monocytogenes were unaffected by
      asphalt fume exposure, lung defenses were sufficient to control the infection. It
      was concluded that acute inhalation of asphalt fumes at a high concentration had
      a minimal effect on lung immune responses to infection in rats.

PMID- 14569498
TI  - Development of an assay for ozone-specific antioxidant capacity.
AB  - A method of determining the ozone-specific antioxidant capacity (OZAC) of lavage
      samples from the respiratory system was developed: Gaseous ozone (O(3)) was
      produced in cuvettes by irradiation with an ultraviolet lamp; aliquots of sample
      or of a saline control were then added and sufficient time was allowed for
      ozonation to reach completion; and an aliquot of indigo trisulfonate (ITS) was
      added to react with excess O(3). Because each molecule of O(3) rapidly bleaches
      one molecule of the deeply colored ITS, an OZAC value in concentration units was
      computed from the difference in light absorbance between the sample and the
      saline control multiplied by the extinction coefficient of ITS. Experiments in 0
      40 micro M antioxidant solutions indicated that the OZAC values of uric acid and
      ascorbic acid were close to their actual concentrations and were independent of
      O(3) concentration. On the other hand, the OZAC of reduced glutathione and
      possibly human nasal lavage were nonlinearly related to antioxidant concentration
      and were directly related to O(3) concentration.

PMID- 14569499
TI  - [Intraocular steroids].

PMID- 14569500
TI  - [Diabetic retinopathy: new treatments].

PMID- 14569501
TI  - [Ocular toxoplasmosis].
AB  - PURPOSE: To update the current concepts in ocular toxoplasmosis. METHODS:
      Interpretation of recent publications, meeting information and personal
      experience. RESULTS: Most important aspects related to transmision of the
      parasite and clinical presentation of the ocular disease are discussed. Special
      issues on diagnosis and therapy are also mentioned. CONCLUSION: A correct
      knowledge of the epidemiology may allow a decrease in the ocular disease and a
      better diagnosis will be possible by recognizing the clinical presentations.
      Therapies have not changed significantly over the last years.

PMID- 14569502
TI  - [Dry eye signs and symptoms in hydrogel contact lens wearers: relation to smoking
      habit].
AB  - PURPOSE: To determine whether there may be a relationship between the smoking
      habit ant the presence of dry eye signs and symptoms in a population of hydrogel
      contact lens (HCL) wearers. MATERIAL AND METHODS: 60 adults HCL wearers were
      chosen randomly. The sample was divided into three groups: nonsmokers, smokers of
      less than 15 cigarettes per day and smokers of more than 15 cigarettes per day.
      The ocular symptoms were evaluated with a questionnaire (modified Mc Monnies
      test). Evaluation of tear meniscus, Schirmer test with anesthesia, non invasive
      break-up time (NIBUT), slit lamp examination and fluorescein staining were
      performed to assess ocular signs of dry eye. RESULTS: No significant differences
      were found among the three study groups. CONCLUSION: Smoking does not seem to
      affect the presence of signs and symptoms of ocular dryness in a population of
      HCL wearers and does not predispose to contact lens intolerance.

PMID- 14569503
TI  - [Orbital vasculonervous network and orbital surgical compartments by high field
      magnetic resonance].
AB  - PURPOSE: To elucidate the possibilities and indications of high-resolution
      magnetic resonance imaging (MRI) in the study of the orbit and its contents.
      METHODS: Orbital anatomy was studied in sliced specimens of fifteen fresh frozen
      cadavers and the results were compared with those obtained in thirty asymptomatic
      subjects who underwent a magnetic resonance with 1.5 Tesla equipment. The
      information obtained was used to interpret the findings in twenty-two patients
      with various orbital diseases. RESULTS: High-resolution MRI allows visualization
      of structures difficult to assess previously, like the cerebrospinal fluid (CSF)
      surrounding the optic nerve, the complete intraorbital route and the exit of the
      third cranial nerve, the ophthalmic artery and the intraorbital relationships of
      the sixth cranial nerve, which can be clearly differentiated from the lateral
      rectus muscle. CONCLUSIONS: High-resolution MRI is a very useful tool for the
      study of the orbit and its content. It provides accurate diagnoses through non
      invasive procedures and facilitates the planning of the surgical approaches by
      improving the visualization of pathologic orbital structures.
      lcarlos@correo.uniovi.es

PMID- 14569504
TI  - [Impression cytology and LASIK].
AB  - PURPOSE: To study the ocular surface changes following laser assisted in situ
      keratomileusis (LASIK). METHODS: Prospective study of pre and post-LASIK
      impression cytology in two sites of the conjunctival epithelium of 12 eyes from 6
      patients. The samples were studied for changes in cellularity, cell size, nucleus
      size, nucleus-cytoplasm ratio, number of goblet cells, PAS positivity and number
      of inflammatory cells. RESULTS: All the samples except two, showed pathological
      changes like a decrease in nuclear size, increase in cytoplasm, change in nucleus
      cytoplasm ratio, a significant decrease in goblet cell density and certain degree
      of squamous metaplasia. CONCLUSIONS: One month following LASIK we observed
      histopathologic changes in the perilimbal conjunctiva, mainly a decrease in the
      number of goblet cells and different grades of squamous metaplasia.

PMID- 14569505
TI  - [Anterior uveitis and juvenile idiopathic arthritis].
AB  - PURPOSE: Anterior uveitis is one of the most important extraarticular
      manifestations of juvenile idiopathic arthritis (JIA). The aim of this study was
      to describe the frequency of uveitis, complications and ocular surgical
      procedures, to corroborate risk factors for the development of uveitis and to
      analyze its evolutive characteristics. METHODS: Retrospective review of 132
      children diagnosed with JIA in our hospital from 1985 to 2000. Patients
      presenting anterior uveitis (Tyndall + or recent keratic precipitates) were
      studied. RESULTS: Uveitis was detected in 26 of 132 children (19%). All of them
      presented pauciarticular JIA. The patients received corticosteroid therapy for a
      mean time of 19.2 months, developing a mean of 4.5 episodes of uveitis. Patients
      diagnosed with uveitis before or within 1 year from the onset of arthritis
      required longer treatment (295 months versus 206) and suffered more episodes (73
      versus 44) than those with uveitis found later on. Complications (cataract, band
      keratopathy, glaucoma, macular edema) developed in 27.9% of the affected eyes.
      Surgery was required in 10 eyes. CONCLUSIONS: The incidence of uveitis in our
      study is similar to recently reported rates. Female sex, pauciarticular onset,
      serum antinuclear antibodies (ANA) and early onset of uveitis seem to increase
      the development of chronic uveitis. Periodic slit-lamp ophthalmologic screenings
      in high risk patients are recommended (Arch Soc Esp Oftalmol 2003; 78: 561-566).

PMID- 14569506
TI  - [Hypotony maculopathy diagnosed by optical coherence tomography].
AB  - CASE REPORT: A 40 year-old man with advanced pigmentary glaucoma in the left eye
      underwent trabeculectomy. In the immediate postoperative period, visual acuity
      decreased with no alterations noted on examination of the fundus or on
      angiofluoresceingraphy. Through optical coherence tomography, we were able to
      make a diagnosis of hypotonic maculopathy and treatment was immediately started.
      DISCUSSION: Hypotony maculopathy is one of the most feared complications of
      filtering eye surgery. In some cases, optical coherence tomography can be useful
      to confirm its diagnosis non invasively.

PMID- 14569508
TI  - [Comments on an ophthalmologic treatise from the 18th century].

PMID- 14569507
TI  - [Choroidal osteoma and choroidal neovascularization].
AB  - CLINICAL CASE: A 27-year-old woman with metamorphopsia was diagnosed with
      choroidal osteoma (CO); concurrently choroidal neovascularization (CNV) was also
      suspected. Neither fluorescein angiography (FA) nor indocyanine green angiography
      showed signs of CNV. A course of oral corticosteroids improved the symptoms, but
      when it was interrupted, both, the ophthalmoscopic and the FA findings showed a
      well defined CNV. Two years following green argon laser photocoagulation the CNV
      is still inactive. DISCUSSION: The clinical and angiographic heterogeneity of the
      CO can delay the diagnosis and treatment of an associated CNV.

PMID- 14569509
TI  - [Transkei].

PMID- 14569510
TI  - [Adjuvant endocrine treatment of breast cancer beyond St. Gallen 2003].
AB  - During the recently held 8th International Conference on Primary Therapy of Early
      Breast Cancer, (March 12-15, 2003 St. Gallen/Switzerland) established
      recommendations for adjuvant endocrine treatment were confirmed, while new
      options were introduced. Ovarian ablation, limited for 2 years (e. g. Goserelin,
      combined with 5 years of Tamoxifen), was suggested as an effective treatment
      option in premenopausal patients with a hormonsensitive breast cancer. The
      efficacy of this endocrine regimen is equivalent to CMF-chemotherapy in these
      patients. In "very" young patients with hormonsensitive tumors, chemotherapy
      alone is not sufficient. These patients will particularly benefit from endocrine
      treatment. The reversibility of endocrine treatment is its main advantage,
      avoiding long lasting symptoms of hormone deficiency. In postmenopausal
      hormonsensitive patients the aromatase inhibitor Anastrozol (Arimidex trade mark
      ) has been approved as an alternative for patients with contraindications against
      Tamoxifen (e. g. increased risk of thromboembolism, varicosis, smokers,
      endometrium changes). The initiation of endocrine should be postponed until the
      completion of chemotherapy, because combined application reduces the efficacy of
      adjuvant treatment. "Older" patients will get only limited advantage of
      chemoendocrine treatment compared to endocrine treatment alone. Preliminary
      treatment recommendations comprise a wide range of possible treatment options.

PMID- 14569511
TI  - [Adjuvant chemotherapy in primary carcinoma of the breast].
AB  - The 2003 St. Gallen consensus on primary therapy of early breast cancer confirmed
      the importance of adjuvant chemotherapy. In endocrine non-responsive tumors,
      chemotherapy is adjuvant treatment of choice, independent of patient age or lymph
      node status. In endocrine-responsive disease, chemotherapy plays an important
      role next to endocrine treatment. The questions, which patients need combined
      chemo-endocrine therapy, and for whom endocrine therapy alone is sufficient, are
      still unsolved. Anthracyclines are standard adjuvant chemotherapy; superiority
      over CMF has only been shown for anthracyclin-containing polychemotherapy with at
      least 3 substances. Recent published evidence suggest that adding taxanes to
      anthracyclin regimens may benefit patient survival and that taxanes are a valid
      therapeutic option in node-positive, hormone receptor negative breast cancer. The
      optimal use of taxanes in different risk collectives is currently being
      investigated in clinical trials. Generally, adjuvant chemotherapy should be
      administered before radiotherapy, and endocrine therapy should be given
      sequentially. In view of the international St. Gallen panel, the final
      publication may only represent a minimal consensus. Individual countries are
      requested to adapt these recommendations to national conditions. In Germany, up
      to-date evidence-based therapy recommendations have just been issued by the AGO
      "breast" expert panel. Interdisciplinary S3 breast cancer guidelines are
      currently being finalized.

PMID- 14569512
TI  - [Primary systemic therapy of carcinoma of the breast - update of the geparduo
      studies].
AB  - Primary systemic therapy represents today the standard of care in patients with
      locally advanced breast cancer and becomes more and more an alternative to
      adjuvant postoperative chemotherapy in patients with operable breast cancer. In a
      subset of large randomized trials it could be shown that sequential schedules
      with more than 4 cycles can reach the highest rates of clinical and
      histopathological complete remissions. In two randomized trials (NSABP B-27,
      Geparduo) using 4 cycles of Adriamycin/Cyclophosphamide followed by 4 cycles of
      Docetaxel significant better results could be obtained in comparison with the
      referring control arm. New approaches try to further individualize chemotherapy,
      either using molecular biological tumor factors or the early effect of some
      chemotherapy cycles. In the Gepartrio study clinical response evaluation after 2
      cycles can identify patients with a high or low chance for a histopathological
      complete remission and further treatment strategies can be developed for these
      different subgroups.

PMID- 14569513
TI  - [Innovative concepts for surgical treatment of the carcinoma of the breast].
AB  - Breast conserving therapy is a stable element in primary breast cancer treatment.
      Conservation and also restoration of the breast improve the outcome concerning
      psychological aspects. Surgical interventions include techniques for classical
      breast conservation as well as oncoplastic procedures like reduction
      mammaplasties and different types of flaps. Theses modern surgical procedures
      should be realised in a breast center.

PMID- 14569514
TI  - Sentinel lymph node biopsy: benefits and limitations.
AB  - Multiple studies have demonstrated that a sentinel node can be identified in most
      women with breast cancer, and that it reliably predicts the status of the
      remaining axillary nodes. Contraindications to the procedure are decreasing with
      experience but further long term follow up is needed.

PMID- 14569515
TI  - [Chemoprevention of breast cancer: a literature review and report on the current
      status in Germany].
AB  - The prevention of breast cancer is increasingly of focus in health-politics
      policies and has gained a valid position in the area of medical intervention.
      Data from a current meta-analysis of all four randomised Tamoxifen prevention
      studies illustrate a reduction of 38 % (Odds ratio 0.62; 95 % CI 0.42-0.89) in
      the incidence of breast cancer. This observation lead to registration of this
      drug in the USA for the prevention of breast cancer in women with a calculated 5
      year risk of > 1.66 %. In addition to Tamoxifen, further substances are currently
      being tested with the aim of improving the therapeutic index whilst reducing
      incidence and mortality rates. These are primarily substances which have proven
      efficacy in the treatment of breast cancer (other antioestrogens, aromatase
      inhibitors and GnRH-analogues) or those whose mechanism of action predict a
      preventative effect (retinoids, phytooestrogens, substitution preparations e. g.
      Tibolone). In Germany, chemoprevention is currently only to be recommended within
      study protocols, as to date no substance is approved in the indication
      'prevention of breast cancer'. A essential contribution to the accrual of valid
      data is the conduct of breast cancer prevention trials. The participation of
      women with high risk of breast cancer in Germany is, in contrast to comparable
      international studies, problematic. Data on the current knowledge and attitude of
      the female population towards such trials (gathered via a questionnaire of the
      DACH in 7 000 women) show that only 19.5 % of the women questioned during a
      consultation with a gynaecologist were aware of the possibility of active
      chemoprevention. However, 55.3 % stated that they would be prepared to take such
      a substance, were chemoprevention possible. Studies for both pre- and post
      menopausal women with increased risk of breast cancer are currently active in
      Germany (GISS and IBIS-II of the study group GABG - German Adjuvant Breast cancer
      Group). An intensive information campaign to raise public awareness of breast
      cancer risk amongst women and their physicians is planned in conjunction with the
      IBIS-II study (www.brustkrebsvorbeugen.de). Latest literature recommendations for
      prevention of breast cancer (Chlebowski et al.) have been assessed.

PMID- 14569516
TI  - [New aspects of carcinoma of the breast therapy and of gynaecological carcinoma
      treatment].
AB  - Dose-dense chemotherapy and high dose chemotherapy have been issued in the
      adjuvant and primary therapy of breast cancer. Should we use GnRH analogues after
      chemotherapy in premenopausal women who have not become amenorrheic through
      chemotherapy? How important are the taxanes in the primary and adjuvant treatment
      of breast cancer? The optimal screening method for women at high-risk for breast
      cancer was addressed as one of the most important topics. Primary and recurrent
      ovarian cancer therapy needs to be improved further. The optimal primary therapy
      for endometrial cancer and cervical cancer with radiotherapy and/or chemotherapy
      was another addressed issue.

PMID- 14569517
TI  - [Clinical experience with percutaneus large-core needle biopsies of the breast
      and evaluation of cytopathological and histopathological results].
AB  - OBJECTIVE: Core needle biopsy (CNB) allows a microinvasive diagnosis of breast
      lesions. We investigated whether imprint cytology of CNB specimens is a useful
      method of rapidly obtaining additional diagnostic information. MATERIAL AND
      METHOD: During five years 46 218 breast examinations for 23 300 patients were
      performed. 563 patients were examined by CNB. The results of imprint cytology
      were compared with the histopathological results. Statistical analysis was done
      for all patients who underwent subsequent surgery. RESULTS: 195 of 563 patients
      were treated surgically. 155 patients exhibited malign lesions. 40 patients
      showed benign breast lesions. Four patients with malign findings in imprint
      cytology and histopathology of CNB were treated conservatively. Imprint cytology
      had a sensitivity of 0.89, specificity of 0.88, positive predictive value of 0.96
      and negative predictive value of 0.67. Histopathology revealed a sensitivity of
      0.90, specificity of 0.95, positive predictive value of 0.98 and negative
      predictive value of 0.70. 364 patients with benign findings in imprint cytology
      and histopathology were controlled subsequently. One of these patients developed
      five month later an invasive ductal tumor. CONCLUSION: Imprint cytology of CNB is
      a reliable method to obtain additional diagnostic information. Inadequate and
      suspicious cases should be evaluated based on complementary diagnostic procedures
      for breast lesions.

PMID- 14569518
TI  - [u-Plasminogen activator (urinary plasminogen activator, urokinase) (uPA) and its
      PA-1 type 1 inhibitor are not only prognostically but also predictively
      significant and support clinical decisions on therapy in primary carcinoma of the
      breast].
AB  - uPA and PAI-1 are the first novel tumor biological prognostic factors in breast
      cancer for which the prognostic impact has been validated at the highest level of
      evidence and hence all evaluation criteria for transfer into clinical practice
      have been fullfilled. Breast cancer patients with high uPA and/or PAI-1 levels in
      their primary tumor tissue have a significantly lower chance for cure than
      patients with low levels of both uPA and PAI-1. Our research that was honored
      with the Schmidt-Matthiesen-Award 2002 shows for the first time that uPA and PAI
      1 are not only prognostic factors but also have a predictive impact with regard
      to response to adjuvant chemotherapy. Patients with high uPA/PAI-1 derive a
      significantly greater benefit from adjuvant chemotherapy than patients with low
      uPA/PAI-1. Benefit from adjuvant endocrine therapy is independent of uPA/PAI-1
      status. The resulting question about the optimal chemotherapy for patients with
      high uPA/PAI-1 is currently being addressed in Germany by the NNBC-3 trial in
      node-negative breast cancer (AGO, EORTC-RBG) as well as the ADEBAR trial in
      patients with 4 or more involved axillary lymph nodes. Moreover, our results
      suggest the use of novel therapeutic agents interfering with the uPA system
      together with conventional chemotherapy in patients with high uPA/PAI-1 already
      in early stage disease.

PMID- 14569519
TI  - [Impact of DNA image cytometry (ICM) parameter and established prognostic factors
      on disease free survival (DFS) and overall survival (OS) of node-negative breast
      cancer (NNBC) patients].
AB  - OBJECTIVE: DNA ICM allows measurement of nuclear DNA content and genotypical
      grading of malignancy. The aim of this study was to prove the prognostic value of
      DNA parameter in comparison to established prognostic factors for DFS and OS.
      PATIENTS AND METHODS: Cytological imprints of 177 unselected primary NNBC
      patients were subjected to ICM. ICM parameter 2cDI, 5cEE, 9cEE, DNA mean value,
      proliferation fraction (SG2M) and ploidy were investigated together with
      established parameter like pT-stages, histology, grading, hormone receptor status
      and patient age regarding DFS and OS. Univariate and multivariate analysis were
      performed. RESULTS: Univariate analysis revealed that except ploidy all ICM
      parameter and pT-stages, histology as well as grading were significant prognostic
      factors for DFS. However, only 2cDI and pT-stages were proved independent
      prognostic factors in multivariate analysis. Regarding OS 9cEE, histology and pT
      stages were significant factors in univariate analysis. However, only 9cEE and pT
      stages were found to be independent prognostic factors in multivariate analysis.
      CONCLUSIONS: DNA - ICM parameter 2cDI and 9cEE together with pT-stages were
      proved independent prognostic factors in NNBC patients.

PMID- 14569520
TI  - Sleep-disordered breathing in Michigan: a practice pattern survey.
AB  - OBJECTIVES: This survey sought to determine whether self-professed sleep
      specialists in the State of Michigan show practice variations in the diagnosis
      and management of sleep-disordered breathing (SDB), and whether such variations
      occur between pulmonologists and neurologists. METHODS: Questionnaires on
      practice volume and patterns during the prior 12 months were mailed to physician
      members of the Michigan Sleep Disorders Association ( n = 119); 67 were completed
      and returned. RESULTS: Respondents reported that they personally saw a median of
      8 new patients each week for suspected SDB; estimates were that 86% of these
      patients were eventually confirmed to have SDB. Most patients (82%) had
      laboratory-based polysomnography after an initial clinic evaluation, and most
      (69%) of those treated for SDB received continuous positive airway pressure.
      However, practice patterns differed substantially among respondents, even when
      the analysis was limited to the 42 who reported board certification by the
      American Board of Sleep Medicine. For example, among all surveyed practices the
      likelihood that suspected SDB would be evaluated with a split-night diagnostic
      and treatment polysomnogram varied from 0 to 90%. The likelihood of SDB treatment
      with bilevel positive airway pressure varied from 0 to 50%, with automatically
      titrating devices from 0 to 100%, with surgery from 0 to 100% (0 to 50% among
      certified practitioners), and with oral appliances from 0 to 20%. The practice
      patterns of pulmonologists and neurologists did not differ significantly.
      CONCLUSION: Approaches to SDB vary widely in Michigan, though not according to
      clinician background in pulmonary medicine or neurology. A patient's experience,
      in both assessment and treatment, could differ substantially based on which
      clinician is consulted.

PMID- 14569521
TI  - Reactive oxygen metabolites (ROMs) as an index of oxidative stress in obstructive
      sleep apnea patients.
AB  - STUDY OBJECTIVES: Obstructive sleep apnea syndrome (OSA) is accompanied by oxygen
      desaturation and arousal from sleep. Free oxygen radicals are highly reactive
      molecules which could be produced by the OSA phenomenon of hypoxia/reoxygenation:
      cyclical alterations of arterial oxygen saturation with oxygen desaturation
      developing in response to apneas followed by resumption of oxygen saturation
      during hyperventilation. On the basis of these considerations, it was
      hypothesized that OSA may be linked to increased oxidative stress. MATERIAL AND
      METHODS: Twenty-six participants gave an interview during which a physician asked
      them about their age, smoking habits, and symptoms such as excessive daytime
      sleepiness and snoring. Physical examination and polysomnography were performed
      during their hospitalization. Reactive oxygen metabolites (ROMs) were measured in
      blood samples by the diacron reactive oxygen metabolites (D-ROM) test. RESULTS:
      Twenty-one out of 26 subjects had an apnea/hypopnea index greater than 5 (OSA
      group). The measurement of free radicals was high in OSA patients. Furthermore,
      ROMs values in OSA patients were linearly correlated with the apnea/hypopnea
      index (R = 0.426; p = 0.042). The predictive value of a positive D-ROM test is
      81%. CONCLUSIONS: ROMs were elevated in patients with OSA. When OSA was severe,
      similarly the value of ROMs in blood samples was enhanced, and the probable
      underlying mechanism for these events is the hypoxia/reoxygenation phenomenon.

PMID- 14569522
TI  - Endothelin-1 levels in interstitial lung disease patients during sleep.
AB  - BACKGROUND: Hypoxemia stimulates endothelin-1 (ET-1) secretion. The reduction in
      alveolar ventilation during sleep is considered sufficient to account for the
      hypoxemia observed in patients with respiratory diseases. OBJECTIVE: The aim of
      this study was to evaluate the arterial ET-1 levels and their relationship with
      pulmonary hypertension in patients with interstitial lung disease (ILD) during
      sleep. METHODS: We examined 38 patients with ILD using formal polysomnography
      (electroencephalogram, electrocardiogram, airflow, respiratory muscle movement,
      oximeter) to detect the presence of nocturnal, nonapneic, oxyhemoglobin
      desaturation. All patients desaturated below a baseline sleep saturation of 90%
      for 5 minutes or more, reaching a nadir saturation of at least 85%. Each patient
      had already undergone right heart catheterization with a Swan-Ganz catheter for
      measuring hemodynamic parameters. Sampling of arterial blood from a radial artery
      line for determination of blood gases and ET-1 values was performed
      simultaneously, after 5 minutes of the first desaturation. RESULTS: At rest,
      arterial ET-1 levels were higher in ILD patients (1.73 +/- 0.37 mgr/mL) than in
      controls (1.22 +/- 0.15 mgr/mL) ( p < 0.001). Also, the patients with pulmonary
      hypertension (Pa > 20 mm Hg) presented significantly higher arterial ET-1 levels
      (1.86 +/- 0.32 mgr/mL) than those without pulmonary hypertension (1.31 +/- 0.13
      mgr/mL) ( p < 0.001). Arterial ET-1 levels were significantly correlated with
      mean pulmonary arterial pressure (PAP) (r = 0.749, p < 0.001), and arterial
      oxygen partial pressure (PaO2) (r = 0.79, p < 0.001). At sleep, during
      desaturation, arterial ET-1 levels significantly increased in all patients (2.46
      +/- 0.13 mgr/mL) as compared with resting values ( p < 0.001). Arterial ET-1
      levels were significantly correlated with PAP (r = 0.657, p < 0.001) and PaO2 (r
      = 0.93, p < 0.001). CONCLUSIONS: According to our study, arterial ET-1 is
      markedly increased in ILD patients, especially in those with pulmonary
      hypertension.

PMID- 14569523
TI  - A prospective randomized study comparing two different degrees of mandibular
      advancement with a dental appliance in treatment of severe obstructive sleep
      apnea.
AB  - The objective of this study was to compare the effect of two different degrees of
      mandibular advancement (MA), 75% versus 50%, on somnographic variables after 6
      months of dental appliance treatment in patients with severe obstructive sleep
      apnea (OSA). A further purpose was to compare the number of adverse events on the
      stomatognathic system and the effects of dental appliance treatment on the
      presence of daytime sleepiness. Eighty-six males with severe OSA (apnea index >
      or = 20) were randomly allocated to either 75% or 50% MA. Forty patients in the
      75% MA group and 37 patients in the 50% MA group completed the 6-month follow-up.
      The effectiveness of treatment in terms of normalization (apnea index < 5 and
      apnea/hypopnea index < 10) with 75% MA was 52%, which was significantly higher (p
      = 0.04) than the 31% achieved with 50% MA. The dental appliance had few adverse
      events on the stomatognathic system regardless of group, and the number of
      adverse events did not differ between the two groups. Finally, the mean value of
      Epworth Sleepiness Scale scores decreased significantly from 11.6 at baseline to
      8.0 at follow-up (p < 0.001). No significant difference was observed between the
      two groups. The results indicate that a dental appliance could be an alternative
      treatment for some patients with severe OSA.

PMID- 14569524
TI  - Effects of a mandibular protruding device on the sleep of patients with
      obstructive sleep apnea and snoring problems: a 2-year follow-up.
AB  - OBJECTIVES: To evaluate subjective discomfort and somnographic measures of
      patients with obstructive sleep apnea and snoring problems who had been treated
      for 2 years with a mandibular protruding device (MPD). METHODS: The study
      population comprised 65 patients with a pretreatment diagnosis of obstructive
      sleep apnea (OSA) ( n = 44) or habitual snoring without apnea (n = 21). After a
      baseline medical and somnographic examination, a functional examination of the
      stomatognathic system, and a questionnaire focused on sleep-related qualities,
      each patient received an MPD. Two follow-ups were made 6 months and 2 years after
      MPD treatment had been initiated, and all initial examinations were repeated.
      RESULTS: At the 2-year follow-up, significant subjective improvements were
      registered in 90% of the patients regarding a reduction of snoring and apneas, in
      76% regarding a reduction in daytime tiredness, and in 84% regarding an
      improvement in the quality of the night sleep (change of > or = 50% from baseline
      data). At the 2-year follow-up of the OSA group, the oxygen desaturation index
      (ODI) had dropped significantly from a mean value of 14.7 (SD, 12.7) to 3.1 (SD,
      4.2) ( P < 0.001), and the mean SaO2 nadir rose from 78.2% (SD, 8.1) to 89.0%
      (SD, 4.7) ( P < 0.001). Only one of the snorers increased his ODI value; the
      others retained their initial healthy values. The OSA patients significantly
      reduced the amount of time they snored during their sleep. CONCLUSION: MPD
      treatment is associated with a significant reduction in subjective complaints
      such as disturbing snoring, apneas, daytime tiredness, and poor quality of night
      sleep, and with a significant reduction in ODI values in the OSA group. In
      addition, favorable 6-month results were unchanged after 2 years.

PMID- 14569525
TI  - Expiratory-synchronized sleep in a quadriplegic patient using inspiratory neck
      muscles to breathe.
AB  - In a patient with C3 quadriplegia causing complete diaphragm paralysis who
      developed inspiratory neck muscles (INM) hypertrophy to sustain ventilation,
      spontaneous breathing deeply altered sleep architecture, relegating sleep to the
      expiratory phase of the ventilatory cycle. A polysomnographic recording performed
      during mechanical ventilation (without INM activity), showed that sleep was
      abnormal but unaffected by the respiratory cycle. During spontaneous breathing,
      the polygraphic recordings showed expiratory microsleep episodes, with
      inspiratory arousals synchronous to bursts of INM activity. This case report
      illustrates the powerful adaptability of the respiratory and sleep control
      systems to maintain each vital function.

PMID- 14569526
TI  - Multiple sleep latency test by polysomnography: a case report.
AB  - Obstructive sleep apnea syndrome may disguise the presence of other less common
      but equally important etiologies of sleepiness in patients presenting to sleep
      disorder specialists. In this case report the authors detail how multiple
      polysomnograms performed over 6 years eventually suggested that a patient had
      both obstructive sleep apnea and narcolepsy.

PMID- 14569527
TI  - [A new ILO! Guideline through the maze].

PMID- 14569528
TI  - [Further development of the International Pneumoconiosis Classification--from ILO
      1980 to ILO 2000 and to ILO 2000/German Federal Republic version].
AB  - The ILO (1980) Classification has been revised during recent years. The new
      version is now available as the International Classification of Radiographs of
      Pneumoconioses (Revised edition 2000). The Guidelines booklet is currently
      available only in English. Those involved felt it was important to maintain
      continuity with the ILO (1980) edition, in particular to retain the standard
      radiographs, despite their restricted quality, so as to ensure comparability with
      earlier national and international data sets. The standard films illustrating
      pleural abnormalities, and 'u'-shadows, have been modified and reconstituted. The
      most important changes relate to assessment of film quality, pleural
      abnormalities, and additional symbols. In Germany, film quality is characterised
      as "+", "+-", "+--" and "u" according to whether the ability to assess
      pneumoconiosis is judged to be unimpeachable ("+") to unusable ("u"). If a film
      is not classified as "+", then written comments regarding defects are required.
      For "diffuse" pleural thickening, the ILO (2000) edition now requires the
      presence also of obliteration of the costophrenic angle. This was not required in
      the earlier (1980) edition and, as previously, is also not stipulated in the
      German version. A minimum width of 3 mm (previously 0-5 mm), coded "a", is
      required both for plaques as well as for the margin to the lateral chest wall.
      Congruence is thus achieved for criteria, which, in German practice, lead to an
      indication of suspect occupational disease. Plaques on the diaphragm are not
      considered for measurement of extent; they are only coded as present or absent.
      If calcification is identified, then this must also be classified and measured as
      a localised plaque. Extent of calcification on its own, previously coded "0" to
      "3", is no longer specified. The following new symbols, illustrated by new
      diagrams, have been introduced: aa = atherosclerotic aorta; at = apical
      thickening; cg = calcified granuloma (or other non-pneumocononiotic nodules); me
      = mesothelioma (already previously differentiated from "ca" on the German record
      sheet); pa = plate atelectasis; pb= parenchymal bands; ra = rounded atelectasis;
      od = other disease. (Examples of the latter are illustrated diagrammatically by
      lobar pneumonia, aspergilloma, goiter and hiatal hernia.) Earlier national
      differences (ILO 1980/German Federal Republic) on particular issues have also
      been agreed among German "double-readers" ["Zweitbeurteiler"]. However,
      conformity between the original (ILO 2000) text and the national (German)
      modified text has been retained in large measure. The detailed descriptions of
      the standard films differ in certain respects from the German (1980) definitions.
      Some revision of individual descriptions of the films are proposed. Except for a
      few differences, agreement was reached here too. The definitive date for the
      change in Germany is expected to be in early 2004. The standard films are already
      available now through ILO offices in Geneva or Bonn (addresses in appendix.)

PMID- 14569529
TI  - [The influence of smoking on clinical manifestation and composition of
      bronchoalveolar lavage in sarcoidosis].
AB  - Sarcoidosis is defined as an inflammatory systemic disease; the characteristic
      morphological feature is the noncaseating granuloma. Typical finding in
      bronchoalveolar lavage (BAL) is a lymphocytic alveolitis with an increased
      CD4/CD8-quotient. A higher frequency of sarcoidosis in non-smokers (NS) than in
      smokers (S) has been reported. The influence of inhalative smoking on
      demographical data, lung function and results of BAL in prospectively selected
      patients with sarcoidosis was investigated. 111 NS (Sarcoidosis stage I/II+III
      48/63) and 44 S (23/21) were included in the study. 16 patients without provable
      pulmonary disease (9 NS, 7 S) served as controls. Patients with sarcoidosis ware
      less often S than NS (28 vs. 72%, p = 0,0001) Controls 44 vs. 56%, p = 0.6
      [chi(2)]). Sarcoidosis S were younger than NS (40.4 +/- 11.9 vs. 45.6 +/- 14.7
      years, p = 0.009). There were no differences in the IVC (in % predicted). There
      was a negative effect of smoking on the course of the IVC (% predicted) with
      incremental age, not seen in the non smoking group (S vs. NS: r = -0.54, p =
      0.001 vs. r = -0.13, p = 0.22). In BAL of Sarcoidosis S there was a lower
      concentration of albumin than of NS (in mg/dl), S vs. NS: 9.5 +/- 5.9 vs. 14.5 +/
      13.4, p = 0.012 and a trend to a less intensive lymphocytic alveolitis (in % of
      BAL-cells, S vs. NS: 29.2 +/- 21.1 vs. 34.1 +/- 18.6, p = 0.099). Influences of
      the smoking on the populations of T-lymphocytes could not be seen. (CD4/CD8-ratio
      S vs. NS 10.0 +/- 11.4 vs. 7. 2 +/- 7.1, p = 0, 25). In conclusion patients with
      sarcoidosis were more often NS than S. S were younger than NS. A protective
      effect of smoking on the course of lung function in sarcoidosis could be
      excluded. In the BAL S demonstrated a lower content of albumin and a trend to a
      less pronounced lymphocytosis and therefore a less pronounced alveolitis than NS.
      Influences of smoking on the distribution of the lymphocytic populations were not
      seen.

PMID- 14569530
TI  - [Evaluation of a structured education programme for patients with COPD under
      outpatient conditions-- a pilot study].
AB  - In contrast to other chronic diseases, such as bronchial asthma, the role of
      patient education in the management of COPD still remains unclear. Therefore, we
      evaluated the efficacy of a structured education programme for COPD-patients
      under outpatient conditions in a prospective pilot study including 21 patients
      with mild to moderate COPD over a period of two years. The main teaching items of
      the programme are: self-control of the disease with regular peak flow
      measurements, the observation of typical symptoms and the patients diary, effects
      and side effects of the medication, correct inhalation technique and the
      patients' ability to change the medication with respect to the actual degree of
      airflow limitation. The frequency of episodes of dyspnoea per day was
      significantly reduced after the first year. Before the training course the
      patients had an average of 1.6 +/- 0.5 episodes of dyspnoea per day, after the
      first year 1.0 +/- 0.5 (p < 0.05). With respect to the year before the
      intervention, the total number of the exacerbations did not change significantly
      in the two years after the participation in the programme, but the number of self
      managed exacerbations increased. Further effects were an improvement of the
      knowledge of the patients about the effects and side effects of the medication:
      before the education the number of correct answers in a multiple choice test was
      9.1%, one year later 68.7% (p < 0.01) and after the second year 70.5% (p < 0.01).
      The self-control of the disease could be improved by regular observation of
      symptoms, peak flow measurements and patients' diary. The number of hospital days
      due to the diagnosis COPD decreased from 10.1 +/- 0.5 days per patient and year
      to 2.1 +/- 0.2 days (p < 0.01) in the first year after the education and remained
      constant with 2.4 +/- 0.6 days (p < 0.01) even in the second year after the
      course. The efficacy of the education programme is still evident two years after
      the training. In comparison to the results one year after the programme we found
      a loss of efficacy in some aspects, particularly in the self-control of the
      disease. In conclusion, structured education programmes under outpatient
      conditions could improve the self management abilities in patients with mild to
      moderate COPD. Randomized controlled trials with a larger sample size are needed
      to confirm the results of this pilot study.

PMID- 14569531
TI  - [Longterm treatment of COPD with theophylline--still a valuable option?].
AB  - In the last decade the interest of pneumologists and therapeutic research has
      been focused on COPD. The increasing morbidity and mortality world wide and the
      important socio-economic impact challenged to improve the therapeutic options.
      New indications like LABA and newly introduced drugs like tiotropium may help to
      ameliorate symptoms, ICS potentially help to protect against exacerbations and to
      suppress components of the inflammatory process even in COPD. A reappraisal of
      the place of theophylline in the stepwise approach to treat these patients seems
      to be useful. This report reviews its effects as bronchodilator and the well
      documented additive effects in combination with betaadrenergics and
      anticholinergics. Further desirable actions of theophylline on the sensation of
      dyspnoea and on exercise capacity, on respiratory muscle function and on the
      cardiovascular performance are discussed but no definite conclusions can be made
      about the clinical utility of these effects. Given that patients are carefully
      selected in terms of benefit and side effects theophylline may remain a valuable
      therapeutic option.

PMID- 14569532
TI  - [Immediate type allergies due to metal compounds: platinum salts].
AB  - Immediate type allergies due to metal compounds containing chromium, nickel,
      cobalt and platinum are rare. However, allergies to platinum salts represent a
      major health hazard in few precious metal refineries and catalyst productions.
      Sensitization can be shown with a highly specific and sensitive skin prick test.
      A dose-response relationship has clearly been established by prospective
      longitudinal studies, however the definition of a valid threshold limit is
      difficult due to the high variability of exposure. Smoking is a predicting
      factor, whereas atopy is not. Prognosis depends on the duration of symptomatic
      exposure in high exposure areas. Secondary prevention (medical surveillance) is
      effective in the prevention of persistent symptoms and bronchial
      hyperresponsiveness.

PMID- 14569534
TI  - [Tuberculosis in ancient Hebrew scrolls].

PMID- 14569535
TI  - Last line of defense, first line of offense: the perianesthesia nurse as
      goalkeeper.

PMID- 14569536
TI  - An introduction to ASPAN's 2003 position statements.

PMID- 14569537
TI  - A position statement for medical-surgical overflow patients in the PACU and
      ambulatory care unit.

PMID- 14569538
TI  - A position statement on visitation in phase I level of care.

PMID- 14569539
TI  - A position statement on smallpox vaccination programs.

PMID- 14569540
TI  - Screening high-risk patients for the ambulatory setting.
AB  - Screening patients for ambulatory surgery is a team effort that requires
      diligence by all staff members to elicit information through the use of good
      communication skills as well as a thorough screening tool. A careful review of
      body systems is a must, with focused attention on vital organ systems. When a
      holistic approach is used, the true picture of the patient's needs and concerns
      emerges. This article reviews the importance of diligent preoperative screening
      of high-risk patients for the ambulatory surgical care setting. The primary focus
      is on patients with cardiac disease, obesity, and sleep apnea.

PMID- 14569541
TI  - Negative pressure pulmonary edema--a postanesthesia emergency.
AB  - Negative pressure pulmonary edema (also known as postobstructive pulmonary edema)
      is one form of noncardiogenic pulmonary edema that can occur following any
      general anesthetic in which the patient was intubated. This complication can be
      severe, resulting in death if not diagnosed and treated promptly. This review
      explains the cause, incidence, symptomatology, and treatment of patients with
      this form of noncardiogenic pulmonary edema. A case study is also included to
      highlight how a patient may present with this complication in the PACU. This
      article is meant as a review and resource to nurses caring for postanesthesia
      patients in the PACU, ICU, or surgical floor because documented cases of negative
      pressure pulmonary edema have occurred as late as 6 hours postoperatively.

PMID- 14569542
TI  - Postoperative recovery at home after ambulatory gynecologic laparoscopic surgery.
AB  - The purposes of this descriptive, correlational study were to measure pain,
      fatigue, and functional limitations affecting the "at home" recovery process for
      ambulatory gynecologic laparoscopic surgery and to explore the relationships
      between these variables and the return to normal activities. Subjects (N = 91)
      recorded daily ratings of pain, fatigue, and function on a Home Recovery Log for
      6 days postoperatively. The findings indicate that 95% of subjects resumed basic
      self-care activities such as dressing, bathing, and eating by postoperative day
      (POD) 3; however, less than 40% of subjects were able to perform other role
      functions such as shopping, laundry, and work outside of the home. A logistic
      regression model indicated that pain ratings and functional status on POD 2 were
      the best predictors of subjects who would need more than 5 days to resume their
      usual activities and routines. The findings have implications for preoperative
      teaching and telephone follow-up for ambulatory surgery patients. Preoperative
      teaching should prepare women for the additional days needed for recovery of
      instrumental activities of daily living to enable them to make alternate plans as
      necessary. Furthermore, because pain on POD 2 was the single most significant
      predictor of delayed recovery, moving the follow-up phone call from the morning
      to the late afternoon of POD 1 may help the nurse to identify patients who will
      need extra assistance with pain management.

PMID- 14569544
TI  - Perianesthesia care of the patient with gastroesophageal reflux disease.
AB  - Every day millions of people suffer heartburn and other related symptoms of
      gastroesophageal reflux disease (GERD). Because symptoms can lead to a reduced
      quality of life, GERD sufferers are desperate for relief. This article explores
      the definition and pathophysiology, clinical manifestations, diagnostic
      procedures, and treatment options for GERD, including lifestyle modifications,
      medications, surgery, and alternative procedures. It also discusses preoperative,
      anesthesia/intraoperative, and postoperative special care considerations for the
      surgical patient with GERD.

PMID- 14569545
TI  - Leadership at the bedside.

PMID- 14569547
TI  - The service side of care delivery: part 3 "what's my attitude?".

PMID- 14569546
TI  - The Joint Commission on Accreditation of Healthcare Organizations revises
      standards for 2004.

PMID- 14569548
TI  - Understanding evidence-based practice.

PMID- 14569550
TI  - In the midst of change.

PMID- 14569556
TI  - Robert Alan Good, MD, PhD.

PMID- 14569557
TI  - National Marrow Donor Program HLA-matching guidelines for unrelated marrow
      transplants.

PMID- 14569558
TI  - Ex vivo fludarabine exposure inhibits graft-versus-host activity of allogeneic T
      cells while preserving graft-versus-leukemia effects.
AB  - Allogeneic donor T cells in bone marrow transplantation (BMT) can contribute to
      beneficial graft-versus-leukemia (GVL) effects but can also cause detrimental
      graft-versus-host disease (GVHD). A successful method for the ex vivo treatment
      of donor T cells to limit their GVHD potential while retaining GVL activity would
      have broad clinical applications for patients undergoing allogeneic hematopoietic
      cell transplantation for malignant diseases. We hypothesized that donor
      lymphocyte infusions treated with fludarabine, an immunosuppressive nucleoside
      analog, would have reduced GVHD potential in a fully major histocompatibility
      complex-mismatched C57BL/6 --> B10.BR mouse BMT model. Recipients of fludarabine
      treated donor lymphocyte infusions (F-DLI) had significantly reduced GVHD
      mortality, reduced histopathologic evidence of GVHD, and lower inflammatory serum
      cytokine levels than recipients of untreated DLI. Combined comparisons of GVHD
      incidence and donor-derived hematopoietic chimerism indicated that F-DLI had a
      therapeutic index superior to that of untreated DLI. Furthermore, adoptive
      immunotherapy of lymphoblastic lymphoma using F-DLI in the C57BL/6 --> B10.BR
      model demonstrated a broad therapeutic index with markedly reduced GVHD activity
      and preservation of GVL activity compared with untreated allogeneic T cells.
      Fludarabine exposure markedly reduced the CD4+CD44(low)-naive donor T-cell
      population within 48 hours of transplantation and altered the relative
      representation of cytokine-producing CD4+ T cells, consistent with T-helper type
      2 polarization. However, proliferation of fludarabine-treated T cells in
      allogeneic recipient spleens was equivalent to that of untreated T cells. The
      results suggest that fludarabine reduces the GVHD potential of donor lymphocytes
      through effects on a CD4+CD44(low) T-cell population, with less effect on
      alloreactive T cells and CD4+CD44(high) memory T cells that are able to mediate
      GVL effects. Thus, F-DLI represents a novel method of immune modulation that may
      be useful to enhance immune reconstitution among allograft recipients with
      reduced risk of GVHD while retaining beneficial GVL effects.

PMID- 14569559
TI  - Haploidentical stem cell transplantation with purified CD34 cells after a
      chemotherapy-alone conditioning regimen.
AB  - We investigated whether a novel chemotherapy-alone conditioning regimen would
      permit durable engraftment of standard doses of CD34+ purified stem cell grafts
      from full-haplotype mismatched related donors. We also examined the role of
      infusing limited doses of donor leukocytes for prevention of leukemia relapse.
      Our conditioning regimen consisted of thiotepa, fludarabine, rabbit antithymocyte
      globulin, melphalan, cyclosporin, and prednisolone. Since October 1998, 14
      patients with high-risk leukemia were treated; 13 donor-patient pairs shared 3 of
      6 HLA antigens, and 1 pair shared 5 of 6 HLA antigens. A median of 5.4 x 10(6)
      CD34+ cells per kilogram, 1.62 x 10(4) CD3+ cells per kilogram, and 9.32 x 10(4)
      CD19+ cells per kilogram were infused. T-cell depletion was the only graft-versus
      host disease (GVHD) prophylaxis. All patients had prompt engraftment, and no late
      graft rejections were observed. All surviving patients received at least 1
      infusion of donor whole blood containing 5, 7, 10, 25, or 50 x 10(3) CD3+ cells
      per kilogram between days 25 and 95 after transplantation, after which 8
      developed acute GVHD (3 grade I, 2 grade II, 2 grade III, and 1 grade IV) and 2
      developed a bronchiolitis obliterans-like syndrome. After attaining complete
      remission, 5 patients relapsed and died with active leukemia. The estimated
      relapse-related mortality at 4 years is 38.1%. As of June 15, 2003, 6 of 14
      patients have survived a median of 43.5 months after transplantation with 100%
      donor cells. All 6 surviving patients developed acute GVHD and had a natural
      killer cell mismatch with their donors in the direction of graft versus host. The
      estimated overall survival and event-free survival for the 14 patients at 4 years
      is 41.7% +/- 13.5%.

PMID- 14569560
TI  - High CD34+ cell dose promotes faster platelet recovery after autologous stem cell
      transplantation for acute myeloid leukemia.
AB  - We studied platelet engraftment in 58 patients with acute myeloid leukemia in
      first remission treated with autologous stem cell transplantation (ASCT) to
      determine whether CD34+ cell doses >10 x 10(6)/kg were associated with faster
      platelet engraftment. We compared engraftment rates in patients receiving CD34+
      doses between 5 and 10 x 10(6)/kg (standard-dose ASCT) with those receiving doses
      > or =10 x 10(6)/kg (high-dose [HD] ASCT). We also studied neutrophil engraftment
      rates and platelet and red blood cell transfusion requirements. In multivariate
      adjusted models, the rate of platelet recovery to > or =20,000/microL was 4-fold
      greater among subjects who received HD-ASCT (hazard ratio [HR], 4.1; confidence
      interval [CI], 1.8-9.2; P =.001), with median recovery times of 14 versus 28
      days. The rate of platelet recovery to > or =50,000/microL was 2-fold greater
      (HR, 2.1; CI, 1.3-5.9; P =.01), with median recovery times of 19 versus 46 days.
      Faster platelet recovery resulted in the need for fewer platelet transfusions
      among the subjects who received HD-ASCT (mean transfusions, 3.7 versus 9.8; P
      =.005). Although not statistically significant, neutrophil recovery data in the
      adjusted model suggested a similar effect in the HD-ASCT group, with faster
      engraftment times at absolute neutrophil counts >500/microL (median, 9.2 versus
      12 days; HR, 1.6; CI, 0.69-3.5; P =.29) and absolute neutrophil counts
      >1000/microL (median, 9.5 versus 12 days; HR, 1.3; CI, 0.56-2.8; P =.58).
      Subjects who received HD-ASCT required fewer red blood cell transfusions (4.0
      versus 9.8 units; P =.01). Our findings suggest that CD34+ cell doses >10 x
      10(6)/kg CD34+ result in faster engraftment and fewer red blood cell and platelet
      transfusions.

PMID- 14569562
TI  - Bronchiolitis obliterans in chronic graft-versus-host disease: analysis of risk
      factors and treatment outcomes.
AB  - Bronchiolitis obliterans (BrOb), a late complication of bone marrow
      transplantation (BMT), is associated with chronic graft-versus-host disease
      (GVHD) and is frequently fatal. To identify the risk factors associated with
      BrOb, the factors affecting survival, treatment outcomes, and causes of death of
      patients with BrOb, we retrospectively analyzed 2859 BMT recipients. No cases of
      BrOb occurred among 1070 autologous BMT recipients. Among 1789 allogeneic BMT
      recipients, we identified 47 patients with BrOb. In multivariate analysis, older
      recipients or donors and acute GVHD were significantly associated with the
      development of BrOb. Among patients with BrOb, 5-year survival from the time of
      transplantation was only 10%, versus 40% among allogeneic BMT recipients without
      BrOb. The clinical course of BrOb had a significant effect on survival: 79%
      survived 5 years from the time of BrOb diagnosis if BrOb improved versus 13% if
      there was no improvement after the first-line therapy. Predictors of response
      included older donors and recipients, a previous diagnosis of chronic GVHD, and
      diagnosis of BrOb 6 months after transplantation; each of these significantly
      increased the likelihood of a favorable response to treatment. BrOb had high
      mortality rate of 55%, and pulmonary failure was the leading cause of death. More
      effective BrOb therapy is needed, especially for patients with unfavorable
      presentation.

PMID- 14569561
TI  - Reduced-intensity allogeneic stem cell transplantation for patients whose prior
      autologous stem cell transplantation for hematologic malignancy failed.
AB  - Autologous hematopoietic stem cell transplantation (autoSCT) is an effective
      treatment for patients with various hematologic malignancies. Despite the
      significant improvement in the overall outcome, disease progression after
      transplantation remains the major cause of treatment failure. With longer follow
      up, therapy-related myelodysplasia/acute myelogenous leukemia is becoming an
      important cause of treatment failure. The prognosis for these 2 groups of
      patients is very poor. Allogeneic hematopoietic stem cell transplantation
      (alloSCT) is a potential curative treatment for these patients. However, the
      outcome with conventional myeloablative alloSCT after failed autoSCT is typically
      poor because of high transplant-related mortality. In an attempt to reduce the
      treatment-related toxicity, we studied a reduced-intensity conditioning regimen
      followed by alloSCT for patients with progressive disease or therapy-related
      myelodysplasia/acute myelogenous leukemia after autoSCT. This report describes
      the outcomes of 28 patients with hematologic malignancies who received a reduced
      intensity alloSCT after having treatment failure with a conventional autoSCT.
      Fourteen patients received a hematopoietic stem cell transplant from a related
      donor and 14 from an unrelated donor. The conditioning regimen consisted of low
      dose (2 Gy) total body irradiation with or without fludarabine in 4 patients and
      the combination of melphalan (140 mg/m(2)) and fludarabine in 24. Cyclosporine
      and mycophenolate mofetil were used for posttransplantation immunosuppressive
      therapy, as well as graft-versus-host disease (GVHD) prophylaxis, in all
      patients. All patients engrafted and had >90% donor chimerism on day 100 after
      SCT. Currently, 13 patients (46%) are alive and disease free, 7 patients (25%)
      developed disease progression after alloSCT, and 8 (32%) died of nonrelapse
      causes. Day 100 mortality and nonrelapse mortality were 25% and 21%,
      respectively. With a median follow-up of 24 months for surviving patients, the 2
      year probabilities of overall survival, event-free survival, and relapse rates
      were 56.5%, 41%, and 41.9%, respectively. Six patients (21%) developed grade III
      to IV acute GVHD. Among 21 evaluable patients, 15 (67%) developed chronic GVHD.
      We conclude that (1) reduced-intensity alloSCT is feasible and has an acceptable
      toxicity profile in patients who have previously received autoSCT and that (2)
      although follow-up was short, a durable remission may be achieved in some
      patients who would otherwise be expected to have a poor outcome.

PMID- 14569563
TI  - The role of cytotoxic therapy with hematopoietic stem cell transplantation in the
      treatment of diffuse large cell B-cell non-Hodgkin's lymphoma.

PMID- 14569568
TI  - Traumatic atlanto-occipital luxation in a dog: associated hypoglossal nerve
      deficits and use of 3-dimensional computed tomography.
AB  - OBJECTIVE: To present a detailed description of a dog with atlanto-occipital (A
      O) luxation, including results of the neurologic examination, diagnostic imaging,
      and treatment by closed reduction. STUDY DESIGN: Clinical case report. SAMPLE
      POPULATION: One adult intact male German shepherd dog. RESULTS: Neurologic signs
      included nonambulatory tetraparesis and neck pain. An apparent hypoglossal nerve
      deficit was consistent with a lesion at the peripheral part of the nerve in the
      region of the craniocervical junction. Radiographic examination revealed a left
      sided luxation of the A-O joint, and fractures were excluded with the aid of
      computed tomography (CT). Closed reduction of the luxated articulation resulted
      in a stable A-O joint, and complete neurologic recovery occurred within 4 weeks.
      CONCLUSIONS: Hypoglossal nerve deficits may be associated with A-O luxation.
      CLINICAL RELEVANCE: Closed reduction of a unilateral, traumatic luxation of the A
      O joint is a therapeutic option in dogs. CT imaging, especially 3-dimensional
      reconstruction, was considered helpful in excluding fractures as well as defining
      treatment options.

PMID- 14569569
TI  - Scapulohumeral arthrodesis in miniature horses.
AB  - OBJECTIVES: To describe surgical arthrodesis of the scapulohumeral joint and to
      evaluate its efficacy in reducing morbidity associated with severe shoulder
      dysfunction in miniature horses. STUDY DESIGN: Retrospective study. ANIMALS: Four
      miniature horses. METHODS: Medical records and radiographs were reviewed for
      history, physical examination findings, lameness evaluation, radiographic
      evaluation, surgical techniques, postoperative complications, and outcome. A 10-
      or 11-hole, 4.5-mm narrow dynamic compression plate and 4.5-mm cortical screws
      were applied to the cranial surface of the scapula and cranial surface of the
      humerus after osteotomy of the intermediate tubercle. In most horses, 1 or 2
      screws were inserted in lag fashion across the joint, through holes in the plate.
      RESULTS: Scapulohumeral osteoarthritis was diagnosed radiographically in 4
      horses, and 3 horses had concurrent shoulder luxation or subluxation. All horses
      had grade 3 or 4 lameness before surgery, and most improved by 1 to 2 grades
      after surgery. Despite complications of implant failure (2 horses), infection (2
      horses), scapular fracture (1 horse), and atrophy of the shoulder muscles (1
      horse), functional arthrodesis reduced morbidity in all horses. CONCLUSIONS:
      Scapulohumeral arthrodesis facilitates early return to weight bearing in
      miniature horses with severe scapulohumeral joint osteoarthrosis. Despite
      functional gait abnormality, the horses ambulated quite well after surgery.
      CLINICAL RELEVANCE: Scapulohumeral arthrodesis should be considered for
      debilitating conditions of the shoulder joint in miniature horses, especially
      when the intended outcome is breeding or pasture soundness.

PMID- 14569570
TI  - Healing characteristics of deep digital flexor tenorrhaphy within the digital
      sheath of horses.
AB  - OBJECTIVE: To describe the healing characteristics of deep digital flexor
      tenorrhaphy within the digital sheath. STUDY DESIGN: Experimental study. ANIMALS:
      Five mature horses. METHODS: Right thoracic limb, deep digital flexor tenorrhaphy
      was performed within the digital sheath. Limbs were cast in partial flexion using
      a short limb cast for 6 weeks. Next, extended heel shoes were used for limb
      support for 14 weeks. Healing was evaluated by sequential ultrasonographic
      examinations, and limb use was evaluated by force plate analysis. At 26 weeks,
      mechanical strength and morphologic characteristics of the repair site were
      evaluated. RESULTS: Gap (mean, 0.93 cm.) formation was evident in unloaded limbs
      at 3 weeks. This increased markedly by 6 weeks and was 5 cm at 26 weeks.
      Demarcation between the deep and superficial flexor tendons decreased as the
      transected ends adhered to the dorsal surface of the superficial flexor tendon.
      The intrathecal space was reduced by fibrous tissue. Mean maximum load to failure
      of the repair tissue was 4,616 +/- 3,556 N, with a mean stress of 12.99 +/- 2.78
      MPa. The repair consistently failed at the adhesion between the transected tendon
      and the superficial flexor tendon. CONCLUSIONS: Intrathecal tenorrhaphy with
      external coaptation (in partial limb flexion) for 6 weeks resulted in gap
      healing, fibrous adhesion between the deep and superficial flexor tendons,
      fibrous tissue reduction of the intrathecal space, and a pasture-sound horse at
      26 weeks. CLINICAL RELEVANCE: Without improved methods for immobilizing the deep
      digital flexor tendon, intrathecal tenorrhaphy is unlikely to result in first
      intention tendon healing.

PMID- 14569571
TI  - Mechanical comparison of 3 different clamp and 2 different rod types of a new
      veterinary internal fixation system, 4.5/5.5-mm VetFix.
AB  - OBJECTIVE: To compare the gripping force of a standard clamp with click-on and T
      clamps of the 4.5/5.5-mm VetFix (AO Research Institute, Davos, Switzerland),
      mounted on smooth and roughened rods. STUDY DESIGN: In vitro mechanical study.
      METHODS: Rods were mounted on a clamp-holding device. Each clamp type was tested
      on a materials-testing machine in groups of 6 specimens for torsional and axial
      load stability on smooth and roughened rods (total, 72 specimens). The variable
      evaluated was the discontinuity point (DP) as a measure for gliding resistance of
      the clamp on the rod. Means (+/-SD) were calculated for all groups separately.
      For statistical comparison, a multiple regression model was fitted with level of
      significance set at P =.05. RESULTS: The direction of torsion had a significant
      effect on DP for both asymmetric clamps (standard, click-on). In torsion and
      axial load, the roughened rod had significantly higher DP levels than the smooth
      rod for the standard clamp. Rods differed only in axial load for the T clamp,
      again favoring the roughened rod. The click-on clamp did not reach 10% of the
      values achieved by the other clamps, independent from the rods and loading
      conditions. Compared with the T clamp, standard clamp DP values were
      significantly higher in torsion on the roughened rod as well as in axial load on
      both rod types. CONCLUSIONS: The roughened rod with a standard clamp was
      mechanically superior. For the T clamp, the small loss of gripping force may be
      compensated for by the possibility of inserting 2 more screws. CLINICAL
      RELEVANCE: The roughened rod may enhance the bending, compressive, and torsional
      properties of the 4.5/5.5-mm VetFix system by reducing the risk of clamp gliding
      on the rod. The standard clamp is the clamp of choice, except for the metaphyseal
      or epiphyseal region, at which use of a T clamp may be indicated to increase the
      number of screws inserted at the end of the rod.

PMID- 14569572
TI  - An in vivo equine forelimb model for short-term recording of peak isometric force
      in the superficial and deep digital flexor muscles.
AB  - OBJECTIVE: To develop and test an experimental model for in vivo short-term
      recording of peak isometric forces of the digital flexor muscles in the forelimb
      of adult horses. STUDY DESIGN: In vivo experimental study. SAMPLE POPULATION:
      Four healthy, anesthetized, adult Thoroughbred horses (3 to 7 years old; 527 +/-
      87 kg) METHODS: In dorsal recumbency, ulnar and median nerves were exposed and
      instrumented with insulated bipolar cuff stimulation electrodes for later
      connection to an electrical stimulator. In left lateral recumbency, a biplanar
      fixator was applied to the right humerus and a custom-made, rigid, aluminum frame
      connected to it, to allow loading of muscles distal to the fixator. Threaded
      transfixation pins through the radial and metacarpal condyles were clamped to the
      rigid frame so that the humerus, radius, ulna, and metacarpus were fixed in
      position. Each digital flexor muscle insertion tendon was transected just above
      the metacarpophalangeal joint, extracted from the carpal canal, and secured in a
      metal clamp positioned at the distal myotendinous (MT) junction. Distally, the
      clamp was connected in series to a load cell and a pneumatic actuator to record
      force and to maintain muscle length during nerve stimulation. A linear
      potentiometer was connected in parallel to the actuator to record MT junction
      position. Initial trials were conducted to identify median and ulnar nerve
      stimulation variables to achieve maximal muscle contraction. Isometric
      contractions were performed at different muscle lengths and peak forces
      registered during 3 seconds of supramaximal dual (ulnar and median) nerve
      stimulation. RESULTS: A stimulation voltage of 2.5 to 5.0 V at 50 Hz usually
      produced maximal force for both the superficial digital flexor (SDF) and deep
      digital flexor (DDF) muscles. Single ulnar and median nerve stimulation elicited
      force development not only in the DDF muscle but also in the SDF muscle. At
      voltages higher than 1 V, normalized force was greatest with combined median and
      ulnar nerve stimulation for both the DDF and SDF muscles; however, normalized
      force was greater for median nerve stimulation than ulnar nerve stimulation in
      the DDF muscle, and the opposite relationship was observed for the SDF muscle.
      Final recording of dual supramaximal nerve stimulation of SDF and DDF muscles
      resulted in peak isometric forces of 716 +/- 192 N and 1,577 +/- 203 N,
      respectively. CONCLUSIONS: The instrumentation technique and experimental
      protocol enabled recording of peak isometric forces in the SDF and DDF muscles of
      anesthetized adult horses. CLINICAL RELEVANCE: Studies using this model will
      improve knowledge of SDF and DDF muscle mechanics with insight to functional
      implications of the complex architecture of these muscles. Knowledge of the
      dynamic performance of the SDF and DDF muscles would also be useful for the
      development of new treatment strategies for flexor deformities and tendon
      injuries in horses.

PMID- 14569574
TI  - In vitro comparison of equine cancellous bone graft donor sites and tibial
      periosteum as sources of viable osteoprogenitors.
AB  - OBJECTIVE: To compare the osteogenic potential of cancellous bone of conventional
      graft sites with that of one nonconventional site (fourth coccygeal vertebra) and
      to investigate the tibial periosteum as a donor site with respect to osteogenic
      potential. STUDY DESIGN: In vitro osteogenic cell culture system. SAMPLE
      POPULATION: Eight adult horses. METHODS: Cancellous bone or tibial periosteum was
      aseptically collected and cut into bone chips or periosteal strips of 1 to 2
      mm(3) for primary explant cultures. After 2 weeks, primary tissue cultures that
      yielded a population of osteogenic cells were counted and subcultured at 1 x
      10(5) cells/35-mm dish in osteogenic media. After 7 to 10 days, subcultures were
      stained with Von Kossa (VK) to assess mineralized bone nodule formation. VK
      positive bone nodules were counted as osteoprogenitors and compared among 3 donor
      sites, which provided consistent primary osteogenic cells (tuber coxae, fourth
      coccygeal vertebra, periosteum) using ANOVA (P <.05). RESULTS: Sternal and tibial
      bone yielded viable osteogenic cells from 25% and 50% of horses, respectively,
      whereas yields from tuber coxae, coccygeal vertebra, and periosteum were 75%,
      100%, and 100%, respectively. Tuber coxae and periosteum had significantly
      greater numbers of osteoprogenitors compared with fourth coccygeal vertebra.
      CONCLUSIONS: Among the conventional donor sites, tuber coxae most consistently
      yielded viable osteogenic cells with an acceptable percentage of
      osteoprogenitors. Sternal and tibial sites were unreliable in providing
      osteogenic cells. Two new donor sites, the fourth coccygeal vertebra and tibial
      periosteum, were tissues with good osteogenic potential. CLINICAL RELEVANCE: When
      a source of transplantable viable osteoprogenitor cells is desired, use of the
      tuber coxae as a conventional donor site is warranted. Use of tibial periosteum
      or fourth coccygeal vertebra as reliable sources of transplantable
      osteoprogenitors should be considered.

PMID- 14569573
TI  - The relationship between limb function and radiographic osteoarthrosis in dogs
      with stifle osteoarthrosis.
AB  - OBJECTIVE: To evaluate the relationship between limb function and radiographic
      evidence of stifle osteoarthrosis (OA) in dogs. STUDY DESIGN: The relationship
      between force platform data and radiographic OA score was evaluated on 2 separate
      days using regression analysis. Interday variation was also assessed. ANIMALS:
      Forty-one dogs with visible lameness and radiographic evidence of stifle OA.
      METHODS: Force platform data were collected at a velocity of 1.7 to 2.0 m/s for 5
      trials on day 1 and day 8. Radiographs taken on day 1 were scored using a
      previously reported OA scoring system. RESULTS: No significant relationship was
      found between force platform data and OA score. No significant differences were
      found between any day 1 and day 8 force platform values. CONCLUSIONS: Although
      radiographic evidence of stifle OA provides evidence of pathology, it does a poor
      job of representing limb function. In addition, the absence of significant
      differences between day 1 and day 8 values in this population of dogs supports
      use of only a single force platform evaluation before measuring a treatment
      effect. CLINICAL RELEVANCE: The presence of OA in the stifle joint does not
      correlate with clinical function; radiographic outcome should be used cautiously
      as a predictor of clinical outcome.

PMID- 14569575
TI  - Monopolar versus bipolar electrocoagulation in canine laparoscopic ovariectomy: a
      nonrandomized, prospective, clinical trial.
AB  - OBJECTIVE: To compare the effect of using monopolar (MEC) or bipolar
      electrocoagulation (BEC) on surgical time for laparoscopic ovariectomy in dogs
      and to evaluate the influence of age, weight and obesity, and estrus or
      pseudopregnancy on surgical time. STUDY DESIGN: Prospective, nonrandomized,
      clinical trial. ANIMALS: One hundred three female dogs. METHODS: Laparoscopic
      ovariectomy was performed with MEC or BEC by 1 surgeon using a standard protocol.
      Surgical time was recorded for the different procedural stages and was
      statistically evaluated for differences between MEC and BEC (chi(2), Student t
      test, and ANOVA). The influence of significant variables was analyzed using
      multiple linear regression analysis. RESULTS: Mean surgical time was 47 minutes
      (range, 27 to 110 minutes). With BEC, surgical time was significantly shorter (41
      minutes; P <.001) than with MEC (53 minutes). Obesity (56 vs. 42 minutes; P
      <.001) and intraoperative mesovarial bleeding (56 vs. 46 minutes; P =.03)
      increased surgical time. Dog age, estrus, and pseudopregnancy did not
      significantly influence surgical time. CONCLUSIONS: BEC decreased laparoscopic
      ovariectomy time, decreased intraoperative hemorrhage, and, with the technique
      used, facilitated exteriorization of the ovaries. CLINICAL RELEVANCE:
      Laparoscopic ovariectomy can be performed more rapidly when using BEC instead of
      MEC and with less risk of mesovarial hemorrhage.

PMID- 14569577
TI  - Pediatric hospitals are not appropriate for adult admissions.

PMID- 14569576
TI  - Observer variability of tibial plateau slope measurement in 40 dogs with cranial
      cruciate ligament-deficient stifle joints.
AB  - OBJECTIVE: To determine (1) the inter- and intraobserver variability in
      measurement of tibial plateau angle (TPA), (2) whether this inter- and
      intraobserver variability is related to the characteristics of the dog (age,
      size, and amount of degenerative joint disease [DJD]) and the experience level of
      the observer, and (3) the extent of any relationship between interobserver
      variability of TPA and the variability of the observers' selection of the
      specific cranial and caudal points along the tibial plateau. STUDY DESIGN:
      Examination of tibial radiographs of 40 dogs clinically affected with a cranial
      cruciate ligament (CrCL)-deficient stifle joint. METHODS: Eleven different
      observers, divided into 3 groups based on their level of experience with the
      tibial plateau leveling osteotomy (TPLO) technique, measured the TPA on all 40
      radiographs on 5 different occasions. The degree of DJD present in the stifle
      joint was independently graded as an overall measure and then again as it
      specifically related to the cranial and caudal points along the tibial plateau.
      The total observed variabilities of the TPA were assessed with reference to
      interobserver differences, intraobserver differences, and among the groups of
      observers with respect to the different dog characteristics. Finally, the
      specific points selected on the radiographs were reexamined to determine whether
      any variability was present in cranial and caudal point selection. RESULTS: The
      interobserver standard deviation of the TPA measurements for each dog was 0.8
      degrees, and the intraobserver standard deviation was 1.5 degrees. The TPA
      measurements obtained by the 11 observers differed significantly from each other
      (P <.001); however, there was no significant difference of TPA among the
      different groups of observers (P =.67). There was no significant correlation
      observed between either the inter- or intraobserver variability and the dog
      characteristics. Specific point data and their relationship to the various
      variables of dog characteristics and inter- and intraobserver TPA variability
      revealed significant correlations only to the amount of DJD present at the caudal
      point (P =.001). CONCLUSIONS: Interobserver variation, but no significant group
      variation, was present. Overall DJD did not appear to be related to the
      variability in TPA angle measurement. Most of the interobserver variability was
      attributable to variability in horizontal point selection at both the cranial and
      caudal points and vertical point selection at the caudal point. It appears that
      degenerative changes that specifically obscure the points on the tibial plateau,
      especially at the caudal point, are responsible for most of the interobserver
      variation. CLINICAL RELEVANCE: The desired postoperative TPA of 5 degrees is
      dependent on a precise initial measure of TPA preoperatively. This study
      indicates that there is statistically significant interobserver variability with
      measurement of TPA, which, therefore, can result in a similar amount of
      variability with the final tibial plateau slope obtained postoperatively.

PMID- 14569578
TI  - Comparison of fears and coping strategies reported by Nepalese school-age
      children and their parents.
AB  - This study explored the self-reported fears and coping strategies of Nepalese
      school-age children and their parents' perceptions of their children's fears and
      coping strategies. Seventy-nine healthy school-age children attending a private
      school in Nepal and 48 parents participated in the study. The scores on the Child
      Medical Fear Scale (CMFS) indicated that children had moderate levels of fear. On
      the Schoolagers' Coping Strategies Inventory (SCSI), children reported using
      coping strategies less frequently and found them less effective than those
      reported by their parents. No significant correlations were found between fear
      scores and coping strategies. Significant differences were found between level of
      fears reported by school-age children and parents. No significant difference was
      found between children's and parent's report of children's coping strategies.
      However, a significant difference was found between effectiveness of coping
      strategies reported by children and parents. Nurses need to gather information
      from children, as well as from parents, about fears and coping strategies.
      Nursing intervention should be culturally sensitive with an awareness of cultural
      influences impacting how children perceive fears and cope with their fears.

PMID- 14569579
TI  - Pediatric temperature measurement and child/parent/nurse preference using three
      temperature measurement instruments.
AB  - This study compared the tympanic thermometer with the electronic and chemical dot
      thermometers used at the axillary site and evaluated child, parent, and nurse
      preferences for method of temperature measurement. The child's (n = 146)
      temperature was measured using each of the three methods. Each child, parent, and
      nurse was asked to select a preference for device and site. Results were analyzed
      using the Bland-Altman method. Results showed that most of the paired readings
      fell within the Bland-Altman limits of agreement (LOA). When the chemical dot and
      tympanic temperature readings were compared with the electronic axillary reading,
      the tympanic thermometer was found to be in closer agreement. The chemical dot
      thermometer placed in the axilla consistently read higher than the electronic
      thermometer in the same site. Children, parents, and nurses preferred the
      tympanic thermometer.

PMID- 14569580
TI  - Conducting school-based focus groups: lessons learned from the CATS project.
AB  - Participation of children in focus groups has received scant attention despite
      the effectiveness of group interviews in eliciting children's views. Focus groups
      are a valuable approach for generating qualitative data from children; however,
      conducting school-based focus groups involves challenges specific to the school
      milieu and the ages and development of the participants. Lessons learned from
      conducting school-based focus groups during the Child-Adolescent Teasing Scale
      (CATS) project are applied to examination of key issues including entry to
      schools, informed consent and confidentiality, students' cognitive development,
      safety within the group, and appropriate procedures.

PMID- 14569581
TI  - Mothers in postdivorce families caring for a child with cystic fibrosis.
AB  - This study explored the experiences of mothers of children with cystic fibrosis
      (CF) in postdivorce family structures. In-depth interviews of mothers were
      conducted by registered nurses with expertise in CF. Interviews focused on
      responsibility for care of the CF child within the context of postdivorce
      families (e.g., extent of nonresidential fathers' involvement in children's care,
      communication between households). Interviews were audiotaped and transcribed
      verbatim. The constant comparison method was used for analyzing interview data.
      Marital transitions contributed to the closeness between mothers and children
      with CF, but they also added to the mothers' sense of being overwhelmed with
      responsibilities. It is likely that children and mothers are more at risk for
      stress-related problems when mothers are overburdened by the demands of
      caregiving, earning a living, and other responsibilities.

PMID- 14569582
TI  - U.S. policy: keeping children with special needs safe in America.
AB  - This paper reviews the major efforts being made to reform the child welfare
      system for children with special needs who are in protective placements. Barriers
      to finding permanent and loving homes result in putting these children at high
      risk of institutionalization, poor physical and emotional health, and abuse and
      neglect. Education for prospective parents, foster parents and the child service
      provider workforce is necessary to minimize these poor outcomes.

PMID- 14569583
TI  - Poisoning children.

PMID- 14569585
TI  - The meaning of being in ethically difficult care situations in pediatrics as
      narrated by male registered nurses.

PMID- 14569587
TI  - Collaboration of nursing and child life: a palette of professional practice.
AB  - This evidence-based practice (EBP) article begins with a case study background.
      Case studies can be used to illustrate the unfolding of the nursing process, from
      assessment to reassessment, for particular patient care situations. The evidence
      based process, and its importance for successful clinical outcomes, is explicated
      after the case study presentation. This is an example of how EBP is an integral
      part of what we do as healthcare professionals: When we are faced with clinical
      dilemmas, evidence-based tools are there to guide us to solutions. In this
      example, Child Life and Nursing worked collaboratively to identify key clinical
      issues. They consulted with clinical experts within the hospital, and they used
      scientific rationale to select therapeutic interventions to support a patient and
      her family through several crisis situations. The EBP tools, seeking clinical
      expertise and applying research-based interventions, resulted in successful
      outcomes for a complex patient care situation.

PMID- 14569594
TI  - Flattening Drosophila cells for high-resolution light microscopic studies of
      mitosis in vitro.
AB  - Here we briefly review techniques used to flatten cells that otherwise round in
      culture, so that their division can be more clearly analyzed in vitro by high
      resolution light microscopy. We then describe an agar overlay procedure for use
      with isolated Drosophila neuroblasts, which promotes their long-term viability
      while also allowing for correlative studies of the same cell in the living and
      fixed state. This same procedure can also be used to obtain high temporal and
      spatial resolution images of mitosis and cytokinesis in cultured Drosophila
      Schneider S2 cells, which are a popular model for RNAi studies.

PMID- 14569595
TI  - 3-D surface charges modulate protrusive and contractile contacts of
      chondrosarcoma cells.
AB  - Up to now, most of the studies addressing the critical roles played by protrusive
      and contractile cell-matrix contacts in cell adhesion, guidance, migration,
      matrix assembly, and activation of signaling molecules have been performed on two
      dimensional surfaces. Here, we analysed the organization of chondrosarcoma cell
      contacts in a new three-dimensional environment made of titanium beads. Surface
      charges were modified by deposition of polyelectrolyte multilayer films built up
      by alternated polycations poly-(L-lysine) or poly(allylamine hydrochloride) and
      polyanions poly-(L-glutamic acid) or poly(sodium 4-styrenesulfonate). Negatively
      charged 3-D titanium surfaces amplified the occurrence and length of cell
      protrusions. These protrusions had pseudopod characteristics extended to 200
      microm in length, growing off the substratum to distant beads. Pseudopod
      formation is inhibited by the exocytosis inhibitor concanamycin A and is
      triggered by a secreted factor. Chondrosarcoma cells adhering on uncoated or on
      negatively charged surfaces contained discrete focal spots of vinculin and actin
      cables. In cells plated onto these surfaces, phosphorylation of p44/42 MAPK/ERK
      was twofold increased. In contrast, no cytoskeletal vinculin and actin
      organization was observed when the surface was positively charged. These data
      suggest that chondrosarcoma cells adapt a more stable adhesion on uncoated or
      negatively charged surfaces. This point may be critical in tissue engineering
      strategies designed for cartilage repair.

PMID- 14569596
TI  - CLIC4 is enriched at cell-cell junctions and colocalizes with AKAP350 at the
      centrosome and midbody of cultured mammalian cells.
AB  - CLIC4 is a member of the chloride intracellular channel (CLIC) protein family
      whose principal cellular functions are poorly understood. Recently, we
      demonstrated that several CLIC proteins, including CLIC4, interact with AKAP350.
      AKAP350 is concentrated at the Golgi apparatus, centrosome, and midbody and acts
      as a scaffolding protein for several protein kinases and phosphatases. In this
      report, we show that endogenous CLIC4 and AKAP350 colocalize at the centrosome
      and midbody of cultured cells by immunofluorescence microscopy. Unlike AKAP350,
      CLIC4 is not enriched in the Golgi apparatus but is enriched in mitochondria,
      actin-based structures at the cell cortex, and the nuclear matrix, indicating
      that CLIC4-AKAP350 interactions are regulated at specific subcellular sites in
      vivo. In addition to the centrosome and midbody, CLIC4 colocalizes with AKAP350
      and the tight junction protein ZO-1 in the apical region of polarized epithelial
      cells, suggesting that CLIC4 may play a role in maintaining apical-basolateral
      membrane polarity during mitosis and cytokinesis. Biochemical studies show that
      CLIC4 behaves mainly as a soluble cytosolic protein and can associate with
      proteins of the microtubule cytoskeleton. The localization of CLIC4 to the
      cortical actin cytoskeleton and its association with AKAP350 at the centrosome
      and midbody suggests that CLIC4 may be important for regulating cytoskeletal
      organization during the cell cycle. These findings lead to the conclusion that
      CLIC4 and possibly other CLIC proteins have alternate cellular functions that are
      distinct from their proposed roles as chloride channels.

PMID- 14569597
TI  - Structure of kinetochore fibres in crane-fly spermatocytes after irradiation with
      an ultraviolet microbeam: neither microtubules nor actin filaments remain in the
      irradiated region.
AB  - We studied chromosome movement after kinetochore microtubules were severed.
      Severing a kinetochore fibre in living crane-fly spermatocytes with an
      ultraviolet microbeam creates a kinetochore stub, a birefringent remnant of the
      spindle fibre connected to the kinetochore and extending only to the edge of the
      irradiated region. After the irradiation, anaphase chromosomes either move
      poleward led by their stubs or temporarily stop moving. We examined actin and/or
      microtubules in irradiated cells by means of confocal fluorescence microscopy or
      serial-section reconstructions from electron microscopy. For each cell thus
      examined, chromosome movement had been recorded continuously until the moment of
      fixation. Kinetochore microtubules were completely severed by the ultraviolet
      microbeam in cells in which chromosomes continued to move poleward after the
      irradiation: none were seen in the irradiated regions. Similarly, actin filaments
      normally present in kinetochore fibres were severed by the ultraviolet microbeam
      irradiations: the irradiated regions contained no actin filaments and only local
      spots of non-filamentous actin. There was no difference in irradiated regions
      when the associated chromosomes continued to move versus when they stopped
      moving. Thus, one cannot explain motion with severed kinetochore microtubules in
      terms of either microtubules or actin-filaments bridging the irradiated region.
      The data seem to negate current models for anaphase chromosome movement and
      support a model in which poleward chromosome movement results from forces
      generated within the spindle matrix that propel kinetochore fibres or kinetochore
      stubs poleward.

PMID- 14569598
TI  - Regulation of the transition from vimentin to neurofilaments during neuronal
      differentiation.
AB  - Vimentin (Vm) is initially expressed by nearly all neuronal precursors in vivo,
      and is replaced by neurofilaments (NFs) shortly after the immature neurons become
      post-mitotic. Both Vm and NFs can be transiently detected within the same
      neurite, and Vm is essential for neuritogenesis at least in culture. How neurons
      effect the orderly transition from expression of Vm as their predominant
      intermediate filament to NFs remains unclear. We examined this phenomenon within
      growing axonal neurites of NB2a/d1 cells. Transfection of cells with a construct
      expressing Vm conjugated to green fluorescent protein confirmed that axonal
      transport machinery for Vm persisted following the developmental decrease in Vm,
      but that the amount undergoing transport decreased in parallel to the observed
      developmental increase in NF transport. Immunoprecipitation from pulse-chase
      radiolabeled cells demonstrated transient co-precipitation of newly synthesized
      NF-H with Vm, followed by increasing co-precipitation with NF-L.
      Immunofluorescent and immuno-electron microscopic analyses demonstrated that some
      NF and Vm subunits were incorporated into the same filamentous profiles, but that
      Vm was excluded from the longitudinally-oriented "bundle" of closely-apposed NFs
      that accumulates within developing axons and is known to undergo slower turnover
      than individual NFs. These data collectively suggest that developing neurons are
      able to replace their Vm-rich cytoskeleton with one rich in NFs simply by down
      regulation of Vm expression and upregulation of NFs, coupled with turnover of
      existing Vm filaments and Vm-NF heteropolymers.

PMID- 14569599
TI  - Plasmapheresis as rescue therapy in accelerated acute humoral rejection.
AB  - Accelerated acute humoral rejection (AHR) continues to occur in renal
      transplantation despite improved crossmatching, with potentially devastating
      consequences. Between 1 June 1998 and 31 December 2000, 440 renal transplants
      were performed in our center. AHR was diagnosed by the demonstration of typical
      pathological features on renal histology and positive direct immunofluorescence
      or detection of anti-HLA antibodies in serum. AHR developed in 20 (4.5%) of our
      renal transplant recipients, nine male and eleven female at an average of 16.3
      days post transplantation. All of these patients had a negative current cytotoxic
      crossmatch prior to transplantation. The median serum creatinine at diagnosis was
      5.96 mg/dL, and 83% of these individuals developed oliguric renal failure
      requiring dialysis after having initially attained good graft function (median of
      best serum creatinine before AHR was 2.64 mg/dL). The 18 recipients who had not
      infarcted their grafts at the time of diagnosis of AHR received plasmapheresis in
      conjunction with intensification of their immunosuppressive regimen. This regimen
      was successful in reversing AHR in 78% of those treated with apheresis. In the 14
      responders, graft survival at 6 months was 100% and at 12 months was 91%. Median
      serum creatinine at 6 and 12 months was 1.26 and 1.33 mg/dL, respectively.
      Patients received an average of 8.1 plasma exchanges. However, responders
      received a significantly higher frequency of plasmapheresis (P =.0053), despite
      undergoing a similar number of exchanges overall. Plasmapheresis appears to be an
      effective modality for reversing AHR and maintaining graft function.

PMID- 14569600
TI  - Collection of peripheral progenitor cells in paediatric patients with a new
      programme for the collection of mononuclear cells.
AB  - When harvesting peripheral progenitor cells (PPC) in children, the special
      situation of their circulatory system has to be taken into account. Therefore,
      extracorporeal blood volume and product volume should be small to avoid side
      effects. Nine children (age 2-14 years, weight 12.8-58.5 kg) with malignancies
      underwent 10 PPC collections with the MNC programme of the Amicus blood cell
      separator. The disposable kit was primed with red blood cells (RBCs) or human
      albumin to avoid circulatory side effects. The children were monitored for blood
      pressure and heart rate during the whole apheresis procedure. A median blood
      volume of 4,577 ml (range 3,536-8,596 ml) was processed in a separation time of
      270 min (range 176-331 min). The median product weight was 81 g (range 53-107 g)
      and the yield of CD 34 antigen expressing cells was 12.5 x 10(6)/kg body weight
      (range 1.8-26 x 10(6)/kg body weight). Only one child had to undergo a second
      apheresis to collect the desired transplantation dose. The median platelet
      contamination of the product was 0.32 x 10(11) (0.13-0.85 x 10(11)). No
      circulatory side effects were observed. Blood flow alarms occurred in seven of
      ten aphereses and one collection had to be terminated due to insufficient flow.
      PPC can be efficiently collected in children with the MNC programme without
      circulatory side effects. The platelet contamination of the product was low due
      to the elutriation principle of the collection process, thereby avoiding
      thrombocytopenic bleeding episodes in the patients.

PMID- 14569601
TI  - LDL-apheresis up-regulates VEGF and IGF-I in patients with ischemic limb.
AB  - Although it is known that LDL-apheresis improves ischemic limb seen in patients
      with peripheral arterial occlusive disease (PAOD), the underlying mechanism(s)
      still remains unknown. We studied whether vascular endothelial growth factor
      (VEGF) and/or insulin-like growth factor-I (IGF-I) levels correlated with
      improvement of ischemic limbs after LDL-apheresis. Sixteen patients with PAOD (13
      men, 3 women) were enrolled in our study. LDL-apheresis was performed 10 times
      (treated plasma 3,000 ml) for 5 weeks. Serum level of VEGF significantly
      increased from 262 +/- 171 pg/ml to 306 +/- 165 pg/ml before and after LDL
      apheresis (P < 0.05). This value further increased up to 441 +/- 175 pg/ml 3
      months after the end of this therapy (P < 0.01, compared with the basal value and
      P < 0.05, compared with the value at the end of 10-times session). Increased
      levels of VEGF paralleled increases in the ankle-brachial pressure index (ABI).
      After 10-times therapy, IGF-I significantly decreased (P < 0.05), but increased
      over the basal value 3 months after this therapy. Plasma fibrinogen statistically
      decreased and remained low for 3 months. The favorable effects of LDL-apheresis
      may be ascribed to up-regulation of VEGF and IGF-I associated with decreased
      fibrinogen levels.

PMID- 14569603
TI  - Pulmonary function study of myasthenia-gravis patients treated with double
      filtration plasmapheresis.
AB  - The aim of this study was to investigate the changes in pulmonary function tests
      for patients with myasthenia gravis (MG) after treatment with double filtration
      plasmapheresis (DFP) and to evaluate whether pulmonary function tests predict the
      efficacy of DFP treatment. Thirty-five MG patients (20 females and 15 males, age
      range 21-69 years) underwent DFP for between four and eight consecutive sessions.
      Vital capacity (VC), maximal inspiratory pressure (Pi(max)), and MG score were
      measured before and after DFP. Based on the results of pulmonary function tests,
      the patients were divided into dyspnea (VC < 1.0 L or Pi(max) < -25 cm H(2)O) and
      control groups (VC > 1.0 L and Pi(max) > -25 cm H(2)O). The dyspnea group had a
      significantly better response to DFP treatment, reflected in the decrease of the
      MG-score (P=0.0327), and the increase in VC value (P=0.0561). Higher clearance
      rates of acetylcholine receptor antibody (AchRAb) had a trend toward higher
      changes of VC. In conclusion, VC might better serve as a predictor for the effect
      of DFP in the dyspnea patient group because of better correlation with clinical
      improvement and AchRAb clearance.

PMID- 14569602
TI  - Stem cell mobilization by G-CSF in solid and hematological malignancies: single
      daily dose is better than split dose in obese patients.
AB  - In the past, variable results were reported for single daily and two divided
      daily doses of granulocyte colony-stimulating factor (G-CSF) in stem cell
      collection where no study exists investigating the effect of body mass index
      (BMI) on mobilization. The numbers of CD34(+) cells collected were compared in 86
      patients with solid or hematological malignancies receiving either single daily
      (14 mug/kg/day) G-CSF (filgrastim) as group I (n=36) or two divided doses of G
      CSF daily (2 x 7 mug/kg/day) as group II (n = 50). Both groups were divided into
      subgroups according to their BMI as group a (BMI </=25 kg/m(2)) and group b (BMI
      >25 kg/m(2)). Two groups were similar in terms of BMI, gender, and disease
      characteristics. All patients have received G-CSF as a single or two divided
      doses subcutaneously and aphereses have been done on the 5th day. No significant
      difference in numbers of CD34(+) cells between groups Ia and Ib, groups IIa and
      IIb, and groups Ia and IIa was found. On the other hand, the mean ratio and the
      number of CD34(+) cells in group Ib were significantly higher than those of group
      IIb (0.58 +/- 0.06% vs. 0.37 +/- 0.26%, P = 0.01 and 3.67 +/- 0.65 x 10(4)/kg/ml
      vs. 1.92 +/- 0.37 x 10(4)/kg/ml, P= 0.02). In conclusion, in patients with BMI
      >25 kg/m(2), once daily G-CSF compared to split dose administration induces a
      greater number of CD34(+) stem cell mobilization, which suggests the presence of
      a different pharmacokinetics in obese patients.

PMID- 14569604
TI  - Plasmapheresis for the treatment of acute pancreatitis induced by hemophagocytic
      syndrome related to hypertriglyceridemia.
AB  - Histiocytic cytophagic panniculitis is an unusual form of hemophagocytic syndrome
      related to T-cell lymphoma that can be responsible for hypertriglyceridemia. The
      elevation of serum triglycerides, usually in the setting of familial lipidemia or
      during uncontrolled diabetes mellitus, is a well-recognized cause of
      pancreatitis. We report here on the treatment by plasmapheresis of a patient
      suffering from a T-cell lymphoma-related panniculitis who presented with an acute
      pancreatitis induced by hypertriglyceridemia. The Ranson scoring system at day 2
      was increased and predicted a poor course while clinical features worsened. The
      patient was treated with one plasmapheresis that allowed a dramatic (89%)
      decrease in the triglycerides level. The acute pancreatitis resolved and the
      patient was discharged from the intensive care unit at day 5 with lipids and
      pancreatic enzyme levels within normal range. To our knowledge, this is the first
      case of acute pancreatitis induced by hypertriglyceridemia in the setting of an
      uncontrolled cytophagic histiocytic panniculitis successfully treated by
      plasmapheresis.

PMID- 14569605
TI  - Therapeutic plasma exchange for multidrug intoxication: a case report.

PMID- 14569606
TI  - Vascular access via temporary radial artery catheterization for therapeutic
      plasma exchange.

PMID- 14569607
TI  - Safety of donating multiple products in a single apheresis collection: are we
      expecting too much?
AB  - Modern blood separators rapidly process many liters of donor blood and
      efficiently collect vast quantities of blood components from donors, who may be
      stimulated with potent recombinant hematopoietic growth factors or cytokines.
      Accordingly, the potential risks of modern multiple product/unit apheresis
      donations and recombinant growth factors is analyzed in this report. As is true
      for all medical procedures, risks are associated with apheresis donations. Risks
      of a "standard" apheresis donation, in which one unit of PLTs or plasma is
      collected, are comparable to the risks of whole blood donation. Risks of multiple
      unit apheresis donations, in which either vast quantities of a single blood
      component or multiple units of various components are collected, are incompletely
      understood, particularly, when donors are stimulated with recombinant
      hematopoietic growth factors to increase component yields. To minimize donor
      risks and to increase knowledge of multiple component apheresis donations, both
      short-term problems (e.g., donor reactions accompanying apheresis procedures and
      pre- vs. post-procedure changes in results of donor laboratory studies) and long
      term problems (e.g., medical diagnoses/problems and abnormalities of donor blood
      counts and laboratory test results) should be monitored, ideally, by a repeat
      donor registry. When recombinant hematopoietic growth factors are prescribed,
      donors should give informed consent, and blood center professionals must be aware
      of 1) the effects of these drugs given at pharmacologic, rather than physiologic,
      doses; 2) the differences between the molecular structure of recombinant vs.
      natural/endogenous growth factors; 3) the fact that recombinant growth factors
      have both narrow/focused and broad biological activities; and 4) the probability
      that results of studies in sick/immunosuppressed patients may not be applicable
      to healthy/immunocompetent donors.

PMID- 14569608
TI  - Renal transplantation: basic concepts and evolution of therapy.
AB  - Within the last 5 years, dramatic changes in the area of renal transplantation
      have occurred. There have been shifts in the dominant types of rejection, and in
      the types and utilization of immunosuppressants. Hyperacute rejection is now
      rarely seen, and acute cellular rejection within the first 6 to 12 months has
      been reduced to about 10%. However, humoral/antibody-mediated rejection has
      become a more prevalent problem. In the area of immunosuppressants, the ability
      to reduce acute cellular rejection to about 10% has been achieved through more
      judicious use of calcineurin inhibitors (cyclosporine and tacrolimus), increased
      use of mycophenolate mofetil, and the recent introduction of sirolimus
      (rapamycin). The polyclonal antibody (antithymocyte globulin), as well as
      monoclonal antibodies directed against the alpha chain of CD25 (daclizumab and
      basilixamab), have added substantially to the improved success of renal
      allografts. Because of numerous serious toxicities from glucocorticoids and
      calcineurin inhibitors, particularly cyclosporine, new studies are utilizing
      calcineurin-free and/or glucocorticoid avoidance or rapid elimination protocols
      often in combination with a monoclonal antibody and sirolimus. New
      immunosuppressants such as FTY720 and Campath-1 are also under study. In addition
      to its use in treating patients with low-level donor-specific antibody before
      transplantation in order to avoid hyperacute rejection, apheresis is utilized in
      various combination protocols after transplantation in the management of
      humoral/antibody-mediated rejection, in the treatment of hemolytic uremia
      syndrome that sometimes occurs with calcineurin inhibitors and sirolimus, as well
      as in the treatment of focal segmental glomerulosclerosis that has a major risk
      of recurrence in renal transplants.

PMID- 14569610
TI  - Measuring Solution Viscosity and its Effect on Enzyme Activity.
AB  - In proteins, some processes require conformational changes involving structural
      domain diffusion. Among these processes are protein folding, unfolding and enzyme
      catalysis. During catalysis some enzymes undergo large conformational changes as
      they progress through the catalytic cycle. According to Kramers theory, solvent
      viscosity results in friction against proteins in solution, and this should
      result in decreased motion, inhibiting catalysis in motile enzymes. Solution
      viscosity was increased by adding increasing concentrations of glycerol, sucrose
      and trehalose, resulting in a decrease in the reaction rate of the H(+)-ATPase
      from the plasma membrane of Kluyveromyces lactis. A direct correlation was found
      between viscosity (eta) and the inhibition of the maximum rate of catalysis
      (V(max)). The protocol used to measure viscosity by means of a falling ball type
      viscometer is described, together with the determination of enzyme kinetics and
      the application of Kramers' equation to evaluate the effect of viscosity on the
      rate of ATP hydrolysis by the H(+)-ATPase.

PMID- 14569612
TI  - Two-dimensional DNA displays for comparisons of bacterial genomes.
AB  - We have developed two whole genome-scanning techniques to aid in the discovery of
      polymorphisms as well as horizontally acquired genes in prokaryotic organisms.
      First, two-dimensional bacterial genomic display (2DBGD) was developed using
      restriction enzyme fragmentation to separate genomic DNA based on size, and then
      employing denaturing gradient gel electrophoresis (DGGE) in the second dimension
      to exploit differences in sequence composition. This technique was used to
      generate high-resolution displays that enable the direct comparison of > 800
      genomic fragments simultaneously and can be adapted for the high-throughput
      comparison of bacterial genomes. 2DBGDs are capable of detecting acquired and
      altered DNA, however, only in very closely related strains. If used to compare
      more distantly related strains (e.g. different species within a genus) numerous
      small changes (i.e. small deletions and point mutations) unrelated to the
      interesting phenotype, would encumber the comparison of 2DBGDs. For this reason a
      second method, bacterial comparative genomic hybridization (BCGH), was developed
      to directly compare bacterial genomes to identify gain or loss of genomic DNA.
      BCGH relies on performing 2DBGD on a pooled sample of genomic DNA from 2 strains
      to be compared and subsequently hybridizing the resulting 2DBGD blot separately
      with DNA from each individual strain. Unique spots (hybridization signals)
      represent foreign DNA. The identification of novel DNA is easily achieved by
      excising the DNA from a dried gel followed by subsequent cloning and sequencing.
      2DBGD and BCGH thus represent novel high resolution genome scanning techniques
      for directly identifying altered and/or acquired DNA.

PMID- 14569611
TI  - Application of 4,5-diaminofluorescein to reliably measure nitric oxide released
      from endothelial cells in vitro.
AB  - Here we describe in more depth the previously published application of the
      fluorescent probe 4,5-diaminofluorescein (DAF-2) in order to reliably measure low
      levels of nitric oxide (NO) as released from human endothelial cells in vitro.
      The used approach is based on the following considerations a) use low
      concentrations of DAF-2 (0.1 micro M) in order to reduce the contribution of DAF
      2 auto-fluorescence to the measured total fluorescence, and b) subtract the DAF-2
      auto-fluorescence from the measured total fluorescence. The advantage of this
      method is the reliable quantification of NO in a biological system in the
      nanomolar range once thoroughly validated. Here we focus in addition to the
      previous publication (Leikert et al., FEBS Lett 2001, 506:131-134) on aspects of
      validation procedures as well as limitations and pitfalls of this method.

PMID- 14569613
TI  - Dissecting mitosis by RNAi in Drosophila tissue culture cells.
AB  - Here we describe a detailed methodology to study the function of genes whose
      products function during mitosis by dsRNA-mediated interference (RNAi) in
      cultured cells of Drosophila melanogaster. This procedure is particularly useful
      for the analysis of genes for which genetic mutations are not available or for
      the dissection of complicated phenotypes derived from the analysis of such
      mutants. With the advent of whole genome sequencing it is expected that RNAi
      based screenings will be one method of choice for the identification and study of
      novel genes involved in particular cellular processes. In this paper we focused
      particularly on the procedures for the proper phenotypic analysis of cells after
      RNAi-mediated depletion of proteins required for mitosis, the process by which
      the genetic information is segregated equally between daughter cells. We use RNAi
      of the microtubule-associated protein MAST/Orbit as an example for the usefulness
      of the technique.

PMID- 14569614
TI  - Shotgun Phage Display - Selection for Bacterial Receptins or other Exported
      Proteins.
AB  - Shotgun phage display cloning involves construction of libraries from randomly
      fragmented bacterial chromosomal DNA, cloned genes, or eukaryotic cDNAs, into a
      phagemid vector. The library obtained consists of phages expressing polypeptides
      corresponding to all genes encoded by the organism, or overlapping peptides
      derived from the cloned gene. From such a library, polypeptides with affinity for
      another molecule can be isolated by affinity selection, panning. The technique
      can be used to identify bacterial receptins and identification of their minimal
      binding domain, and but also to identify epitopes recognised by antibodies. In
      addition, after modification of the phagemid vector, the technique has also been
      used to identify bacterial extracytoplasmic proteins.

PMID- 14569615
TI  - An Application of Molecular Genotyping in Mice.
AB  - Microsatellite markers are simple sequence repeats within the mammalian genome
      that can be used for identifying disease loci, mapping genes of interest as well
      as studying segregation patterns related to meiotic nondisjunction. Different
      strains of mice have variable CA repeat lengths and PCR based methods can be used
      to identify them, thus allowing for specific genotypes to be assigned. Molecular
      genotyping offers such identification at any developmental stage, which allows
      for a broad range of anomalies to be studied. We studied chromosomal segregation
      in relation to nondisjunction in early-gestation mouse embryos using molecular
      genotyping. Information on the parental origin as well as the number of
      chromosomes a given progeny carried was obtained in our analysis.

PMID- 14569616
TI  - [Cytogenetic changes in the Namalwa cell line of human malignant lymphoma induced
      by inhibitors of DNA replication and synthesis].
AB  - Namalwa cells originating from the malignant human lymphoma have been analyzed
      cytogenetically upon short-time exposure to subtoxic doses of inhibitors of DNA
      replication and synthesis, either etoposide or fludarabine. The intact cells were
      characterized by the modal class of the chromosomes within the diploid range with
      the proportion of the aberrant cells amounting to 16.0 +/- 0.5%. Upon exposure to
      etoposide the percentage of the aberrant cells increased amounting to 26.1 +/-
      2.9 through 39.8 +/- 1.7% depending on the duration of the exposure and the dose
      of the drug. At the same time the number of the polyploid cells increased but the
      modal class retained within the diploid range. Upon exposure to fludarabine the
      percentage of the cells with the aberrant chromosomes increased to 57.1 +/- 2.9%.
      Two modal classes appeared--the first approaching the diploid number and the
      second being polyploid. The exposure to either etoposide or fludarabine resulted
      in increasing number of the chromatide aberrations with more frequent involvement
      of #1, #2, #5, #6, #7, #11, #13, #14, #16 and #17 chromosomes. The data obtained
      have shown the susceptibility of Namalwa cells to the subtoxic concentrations of
      the inhibitors of DNA synthesis and replication used in the study resulting in
      the survival of the novel clones resistant to the drugs.

PMID- 14569618
TI  - [Effect of aleutian gene on mink (Mustela vison) growth].
AB  - The correlation between the skin size of Mustela vison mink and the combination
      of the alleles of aleutian colour gene has been shown. The studied relation can
      be presented as ppAa > ppAA > ppaa.

PMID- 14569617
TI  - The level of aberrant cells in various tissues of bank vole depending on doses
      and radionuclide balance in organism.
AB  - A regression analysis shows the direct linear relation between 137Cs accumulation
      in rodents and the level of aberrant cells. For 90Sr this trend was negative. The
      dose relationship was the same with 137Cs. The trends were negative 1 month later
      after feeding of animals with clean food. Correspondingly the dose relationship
      was also negative. The levels of cells with apoptosis features were different in
      animals from the control and the radiocontaminated sites. The analysis has
      revealed the correlation between the 90Sr content in animal body and the number
      of alveolar macrophages containing micronuclei. The relationship was revealed
      between the 137Cs content in the animal body and the number of intestinal
      epithelial cells with micronuclei.

PMID- 14569619
TI  - [The number of aberrations in aberrant cells as a parameter of chromosomal
      instability. 1. Characterization of dose dependency].
AB  - Analysis of chromosome instability (CI) is of great importance in view of
      pollution of the environment by genotoxic factors. Frequency of aberrant cells,
      spectrum of chromosome aberrations, damages of aberrant cell and distribution of
      aberrations in the cells are the most conventional parameters of CI. We have
      carried out the comparative analysis of the frequency of aberrant cells and the
      dynamics of aberrant cell damages induced by different mutagenic factors (alpha
      irradiation from 241Am, gamma-irradiation from 60Co and tioTEPA) in Allium-test.
      This comparative analysis denotes that the studied parameters have different
      dynamics characterizing different mechanisms of CI in Allium cepa L.

PMID- 14569620
TI  - [Cellular radioprotective mechanisms to the action of cadmium ions on pea
      seedlings].
AB  - The reaction of pea (Pisum sativum L.) seedlings on the test--action (gamma
      radiation) depending on a phase of seedling reaction on modifying action of
      cadmium ions was investigated. The existence of correlation between growth rate
      of the seedling main root and proliferative activity of root apex meristem and
      the type of radiomodificating effect was established. Radioprotective
      (radioadaptation) effect was observed at the 5 Gy dose irradiation of the
      seedlings at the final moment of hypercompensatory phase of the growth reaction
      on the action of 0.625 MkM CdSO4.

PMID- 14569621
TI  - [Characterization of intra-population genetic polymorphism of the Colorado potato
      beetle using ISSR-markers and phenotypes].
AB  - The level of genetic diversity was estimated in a local population of Colorado
      potato beetle using ISSR-markers and specific pronotum patterns. In contrast to
      the unchanged level of diversity in ISSR, Shannon's diversity index calculated on
      the base of pronotum pattern variants was decreasing during summer testifying
      adaptivity of that sign. The results also show the difference in the level of
      genetic diversity of females comparing to males.

PMID- 14569622
TI  - [Effect of changes in gravity on the quantity and localization of fibrillarin in
      the nucleolus of cress root meristem].
AB  - For the first time, in altered gravity, with antifibrillarin antibodies and
      immunogold microscopy fibrillarin that is one of the most important proteins of
      rRNA processing was localized. The quantitative study of the density of gold
      particles in the nuclelous, under clinorotation both the transition zone FC-DFC
      and the dense fibrillar component were less labeled as compared to the control.
      Obtained data allow us to suppose the lowering of the rRNA processing level in
      the nucleoli under the influence of altered gravity.

PMID- 14569623
TI  - [Genetic collections: problems of formation, conservation and use].
AB  - Classification of plant genepool collections are presented, the principal tasks
      worked on by collections are examined. Databases on genepool collections of the
      Institute of Cytology and Genetics of Syberian Branch of Russian Academy of
      Sciences (Russia) and the National Centre for Plant Genetic Resources of Ukraine
      are described. Principles of formation of genepool collections, their existing
      problems, the methods of maintenance of their viability and genetical
      authenticity are discussed. Necessary amount of collection accessions,
      differences and specificity of their reproduction and multiplication aims and
      tasks are proved. Gradations of the permissible changes of accessions in
      connection with the type and the purpose of collections are proposed. The
      necessity of specialized periodical edition on genepool collecting is emphasized.

PMID- 14569624
TI  - [Phenogenetics of offspring and their ancestors].
AB  - By the help of questionnaire of young peoples (18-25 years) was received an
      information about their psycobiological likeness to mother, father, grandmother,
      grandfather. From 788 girls likeness to mother marked in 50.51%, father--37.06%,
      grandmother--9.77%, grandfather--2.66%. Boys (416 answers) marked likeness in
      34.13% with mother, in 52.64% with father, in 3.85% with grandmother, in 9.38%
      with grandfather. So, the girls more frequent showed there likeness to ancestors
      of women sex, and boys--to men sex. Authors thinking, that this thing is
      conditioned not only by heredity cytoplasmatic factors, but by alternative action
      of womanish and masculine sexual hormones.

PMID- 14569625
TI  - [Genetic control of morphological characters of the beet (Beta vulgaris L.)].
AB  - A brief review of theoretical and practical results of investigation of genetical
      control of a number of traits of beet, including self-incompatibility, monogerm
      multigerm, cytoplasmic male sterility and some others is presented. Data
      concerning linkage groups of individual genes, determining morphological and
      biochemical traits are demonstrated.

PMID- 14569626
TI  - [Formation of varieties of cultured forms of tomato and the principles of their
      taxonomic classification].
AB  - The literature data are summarized confirming the invaluable role of mutation
      process in antropogenic evolution of cultivated tomato forms. It is shown that
      just the presence of mutant characters was the basis for existing botanical
      classification of cultured tomato. Expediency and alternative of existing
      taxonomic conceptions of cultured tomato are discussed.

PMID- 14569627
TI  - CDC report on environmental infection control.

PMID- 14569628
TI  - The medical group pay-for-performance initiative in California and diabetes care.

PMID- 14569629
TI  - Opportunities to improve care and manage costs for employees with chronic
      diseases.

PMID- 14569630
TI  - Diabetes as an opportunity for health plans to improve the quality of care for
      their members.

PMID- 14569631
TI  - A conversation with Margaret O'Kane.

PMID- 14569632
TI  - A clinician's view of the role of insulin and why it should be better used.

PMID- 14569633
TI  - A conversation with Janice Pushaw.

PMID- 14569634
TI  - Improving diabetes care amidst mandates, disease management, and corporate need:
      a pharmacy perspective.

PMID- 14569635
TI  - Cardiovascular risk among HIV-positive patients on antiretroviral therapy.
AB  - Dyslipidemia is now recognized as a significant potential adverse event in HIV
      positive patients who are on ART. The tide of evidence continues to flow between
      the shore of HIV being the primary factor behind increased cardiovascular risk in
      HIV-positive patients, and the ocean of HAART being the primary cause. However,
      there clearly is an association between long-term infection with HIV and
      metabolic abnormalities. HIV-infected adults should undergo evaluation and
      treatment based on the NCEP ATP III guidelines. The NCEP recommends non
      pharmacologic interventions be given a thorough trial prior to consideration of
      drug therapy. The recommendations also stipulate that intensive therapy with
      lipid-lowering medications should be used in individuals with metabolic syndrome.
      This includes aggressive treatment of hypertension, diabetes, and dyslipidemia.
      The NCEP also emphasizes the importance of smoking cessation, weight reduction,
      increased physical activity, and a salubrious diet. The fundamental message still
      is that physicians must treat HIV infection first. The choice of ART depends on
      many patient-specific factors, of which cardiovascular risk is only one.

PMID- 14569636
TI  - Abuse and neglect.... ...so prevalent yet so elusive.

PMID- 14569637
TI  - Most patients with cardiac disease have classic risk factors.

PMID- 14569638
TI  - Chronic foot ulcer. Identifying patient's current topical therapy aids in
      diagnosis.

PMID- 14569639
TI  - Preventing pneumococcal disease. ACIP recommends pneumococcal polysaccharide
      vaccine for all adults age > or = 65.
AB  - Streptococcus pneumoniae remains the most common cause of community-acquired
      pneumonia and bacterial meningitis in older adults. Current recommendations from
      CDC's Advisory Committee on Immunization Practices suggest providing pneumococcal
      polysaccharide vaccine to all adults age 65 and older and to persons age 2 to 64
      with chronic illnesses that place them at higher risk for pneumococcal disease.
      In addition, vaccination status should be assessed for residents of nursing homes
      and long-term care facilities on admission and vaccine administered as needed.
      Although the polysaccharide vaccine is safe, effective against invasive disease,
      and cost-effective, many older adults have not yet received the vaccine. Use of
      standing orders is encouraged as a way to improve vaccine delivery. Research into
      new vaccines to prevent pneumococcal disease in older adults is ongoing.

PMID- 14569640
TI  - Valvular heart disease, Part 2. Mitral valve disease in older adults.
AB  - Mitral valve disease is a common cause of morbidity and mortality in patients
      over age 65. The etiology, physical findings, and natural history of rheumatic
      mitral stenosis, rheumatic mitral regurgitation, chronic non-rheumatic mitral
      regurgitation, and acute mitral regurgitation may differ in older and younger
      patients. In addition, symptoms of mitral valve disease may be masked or
      exacerbated by coexistent coronary artery disease, pulmonary disease,
      hypertension, and other systemic disorders that commonly occur in older adults.
      The clinical evaluation, along with various non-invasive cardiac procedures, is
      important for identifying mitral valve disease as the cause of abnormal signs and
      symptoms in older patients. Recognition of mitral valve abnormalities has
      important implications, because mitral valve repair or replacement is usually
      associated with favorable short- and long-term results, even in patients over age
      65.

PMID- 14569641
TI  - Elder neglect and abuse. A primer for primary care physicians.
AB  - Elder neglect and abuse represent a widespread, largely undiagnosed problem in
      the United States. Factors contributing to misdiagnosis and underreporting
      include denial by both the victim and the perpetrator, clinicians' reluctance to
      report victims, disbelief by medical providers, and clinicians' lack of awareness
      of warning signs. Physical abuse is most recognizable, yet neglect is most
      common. Psychological and financial abuse may be more easily missed. Elder
      neglect and abuse have many clinical presentations, ranging from the overt
      appearance of bruises and fractures, to the subtle appearance of dehydration,
      depression, and apathy. Risk factors are varied and may be categorized by victim
      or perpetrator. Dependency, on the part of the victim or perpetrator, and
      caregiver stress are frequent common denominators in abusive situations.
      Increasingly, Institutionalization is recognized as a risk factor for neglect and
      abuse. Most states require primary care providers to report suspected elder
      abuse. Awareness of the risk factors and clinical manifestations allows primary
      care physicians to provide early detection and intervention for elder neglect and
      abuse.

PMID- 14569642
TI  - Dementia update. Pharmacologic management of agitation and psychosis in older
      demented patients.

PMID- 14569643
TI  - Rivastigmine in subcortical vascular dementia: a randomized, controlled, open 12
      month study in 208 patients.
AB  - Subcortical vascular dementia (VaD) is characterized by executive dysfunction and
      behavioral problems, reflecting deterioration of the frontal lobe. This study
      aimed to determine whether rivastigmine, a dual inhibitor of acetylcholinesterase
      (AChE) and butyryl-cholinesterase (BuChE), has any effects on the typical
      symptoms of subcortical VaD. Patients receiving rivastigmine showed a slight
      improvement in executive functions and in behavior. Side effects in both groups
      were tolerable and there were no study withdrawals. Moreover, there are no drug
      interactions with other therapies previously and concomitantly assumed.
      Improvements in domains that characterize subcortical VaD were observed,
      indicating that rivastigmine may have provided targeted treatment in areas of the
      brain that are particularly affected in this patient population.

PMID- 14569644
TI  - Teaching staff to respond effectively to cognitively impaired residents who
      display self-protective behaviors.
AB  - A randomized controlled trial (RCT) was implemented to evaluate the effectiveness
      of a 7 1/2 hour educational program designed to provide staff with the knowledge,
      skill, and confidence to manage physical self-protective behaviors of cognitively
      impaired long-term care residents. This RCT using a pretest/post-test design was
      conducted using consenting staff members (n = 40) who were randomly allocated to
      either a control or experimental group. The main outcome measure was a skills lab
      that evaluated participants 'responses to simulated patients. Both groups
      participated in the skills lab prior to training, and six weeks after the
      experimental group completed the program. Pre- and post-training and skills lab
      observational field notes were subjected to thematic content analysis. Twenty
      eight staff members completed both pre- and post-training assessment
      measurements. Descriptive statistics and paired t-test analyses yielded
      statistically significant differences in change scores for performance indicators
      in three simulation scenarios. Analysis of the qualitative data support the
      finding that, once trained, staff felt better prepared to manage self-protective
      behaviors. The results suggest that an initiative to educate staff will enhance
      knowledge, improve performance, and provide the confidence necessary for staff to
      respond positively to overt physical behaviors in cognitively impaired elders.

PMID- 14569645
TI  - Health promotion for the mind, body, and spirit: a college course for older
      adults with dementia.
AB  - This article describes a pilot study of an experimental college course for
      individuals with newly diagnosed dementia, with a focus on teaching methods for
      promoting and maintaining optimal health. Community involvement included
      recruitment by the local Alzheimer's Association chapter and an off-campus site
      at a local assisted living center with easy access for the students. Course
      topics covered over the 10-week period, included modules on: physical and
      cognitive fitness, nutrition, recreation, communication, understanding the
      disease process, depression, coping, relationships, and driving issues. Stress,
      depression, self-efficacy, and self-esteem were evaluated both prior to and after
      the 10-week course. Providing education early in the course of the disease,
      empowers the older adult student and provides an element of personal control and
      dignity. The course also attempts to prevent future problems by teaching new
      habits and lifestyles early in the disease process. Attempts to change habits and
      behavior later in the course of the disease often fail due to the difficulty of
      learning new behaviors.

PMID- 14569646
TI  - Measuring and enhancing self-efficacy among professional caregivers of
      individuals with dementia.
AB  - Nurses who provide care for individuals with Alzheimer's disease and other
      dementias are at risk of burnout. Self-efficacy is a psychological construct with
      the potential to help reduce or prevent the impact of caregiver stress. Evidence
      supporting a link between higher levels of self-efficacy and lower levels of
      stress is emerging among lay caregivers. However, concurrent research for
      professional caregivers lags behind, partly due to a lack of appropriate self
      efficacy measures for this population. We developed an intervention to enhance
      self-efficacy and an inventory to measure its improvements among long-term care
      nurses. Training resulted in lasting improvements in knowledge and self-efficacy
      regarding the management of challenging team, resident, and family situations.
      Short-term reductions in caregiver burnout were also evident. Suggestions for
      maintaining improvements in caregiver burnout over longer periods are offered.

PMID- 14569647
TI  - Secondary dementia caregiving and its consequences.
AB  - The purpose of this study was to ascertain variations between primary and
      "secondary" caregivers (those who play a more supplemental role in the care of a
      relative). Survey data were collected from a sample of dementia caregivers
      recruited from the University of Kentucky Alzheimer's Disease Research Center (N
      = 1,016). Bivariate analyses found that primary and secondary caregivers varied
      on a number of background characteristics, and regression models indicated that
      primary caregivers provided a wider range of assistance with instrumental
      activities of daily living (IADLs), but not help with activities of daily living
      (ADLs). Primary and secondary caregivers did not differ significantly in reports
      of subjective health. The findings suggest that future research and interventions
      should be inclusive of primary and secondary caregivers.

PMID- 14569648
TI  - Long-distance caregiving: a case study of an African-American family.
AB  - A growing number of Americans are managing and monitoring long-distance
      caregiving for an elderly parent. The authors offer a first-hand experience of
      caregiving involving an African-American family, which will be useful to both
      caregivers and practitioners. The challenges that result from long-distance
      caregiving are discussed. A detailed case study and assessment is followed by
      suggested strategies for lessening caregiver stress.

PMID- 14569649
TI  - Forgetting: a memoir about culture, language, and religion.

PMID- 14569650
TI  - Small business executives and health insurance: findings from a national survey
      of very small firms.
AB  - Previous researchers have documented that very small businesses (3-24 workers)
      are less likely to offer employees health insurance than larger corporations.
      This study supplements previous findings on the prevalence of health insurance
      among small firms. The authors also attempt to illuminate reasons behind coverage
      decisions by interviewing small business owners and executives, who most often
      make health benefits decisions on behalf of their employees. The study examines
      attitudes about health insurance, opinions, and practices in these very small
      firms, and the response of small business owners to policy alternatives designed
      to expand coverage in small businesses.

PMID- 14569651
TI  - Managing antibiotics in managed care plans.

PMID- 14569652
TI  - Utilization patterns of second-line antibiotics in a health plan setting.
AB  - Increased utilization of second-line antibiotics where first-line agents are
      appropriate, and the use of antibiotics for viral infections, are leading to the
      development of resistance. This retrospective study evaluated antibiotic
      utilization patterns of cephalosporins, macrolides, and quinolones for community
      acquired infections in a health plan's patient population. Patients were
      identified through the health plan's computerized pharmacy claims database.
      Patients were considered eligible if they had been enrolled with the health plan
      for at least one year, and had a prescription claim for a cephalosporin,
      macrolide, or quinolone antibiotic between February 1, 2001 and April 30, 2001.
      Six hundred fifty patients were randomly selected to undergo chart review. A
      total of 128 patients (25.2%) from an eligible cohort of 508 health plan members
      had no documented diagnosis of infection in their chart. Gram staining was
      checked in 14 patients. Cultures were ordered for only 19 patients. Comparisons
      were made with regard to first-, second-, and third-line drug use in select
      documented infections. Of all the patients in the study, only 10.4% (53/508) had
      chart documentation of previous antibiotic failure. Of the 456 patients who had
      documentation, 63% had no known antibiotic allergies, and 19% had allergies to
      penicillin. The results of this study will be used to educate providers and
      consumers on appropriate antibiotic prescribing.

PMID- 14569653
TI  - Opportunities to use personal digital assistants in disease management.

PMID- 14569654
TI  - It's the prices, stupid.

PMID- 14569655
TI  - Antiretroviral resistance in clinical practice.

PMID- 14569656
TI  - The Model State Emergency Health Powers Act: public health and civil liberties in
      a time of terrorism.

PMID- 14569657
TI  - Blinded by bioterrorism: public health and liberty in the 21st century.

PMID- 14569658
TI  - Policy choices and model acts: preparing for the next public health emergency.

PMID- 14569659
TI  - Quarantine redux: bioterrorism, AIDS and the curtailment of individual liberty in
      the name of public health.

PMID- 14569660
TI  - Biodefense: who's in charge?

PMID- 14569661
TI  - Regulation of biological research in the terrorism era.

PMID- 14569663
TI  - Listening for rhetorical truth.
AB  - Associations are rarely as free as theory assumes; at the same time, they may
      tell us more than what appears on the surface. Memories, on the other hand, are
      rarely as reliable as they might appear. We are overtrained to listen to the
      unfolding story and to the narrative truth of the moment; much harder to capture
      is what might be called its rhetorical truth. Learning to listen for sequence,
      repetition, and co-occurrence tends to minimize the importance of the narrative
      thread and clarify instead the more suppressed meanings. In rare cases, we can
      even sense something of what the analysand is saying before it comes into
      awareness.

PMID- 14569662
TI  - The stem cell compromise: a wolf in sheep's clothing, constitutional implications
      of the Bush plan.

PMID- 14569664
TI  - Perverse modes of thought.
AB  - Subtle, nonpsychotic disturbances in thinking may cause significant impairment of
      intellectual functioning and interfere with a patient's capacity to make use of
      psychoanalytic treatment. As these come under interpretive scrutiny, the
      intellectual exchange between patient and analyst may emerge as a theater for the
      enactment of perverse sexual fantasies. In this paper, the author describes these
      disturbances in thinking and proposes a model that explains their underlying
      structure and their link to the associated fantasies. Interpretation and working
      through of the condensed part-object and whole-object transferences that emerge
      in the analysis of these forms of thinking may lead to some measure of clinical
      improvement.

PMID- 14569665
TI  - Time and the psychoanalytic situation.
AB  - Implicitly or explicitly, time dominates the psychoanalytic situation. The
      precision, consistency of duration, and regularity of analytic sessions enhance
      the patient's ego boundaries, counteracting the regressive effects of
      timelessness induced by free association. The extended overall duration of
      psychoanalysis and the high frequency of sessions favor the development of
      transference neurosis. The interpretation of the transference in the here and now
      of the analytic situation illuminates the past, and as a result, the patient's
      self-image and that of the world become better integrated. The sense of time in
      the analytic situation for both patient and analyst varies along with the
      vicissitudes of transference and countertransference.

PMID- 14569666
TI  - On ugliness.
AB  - Ugliness results from the emergence into consciousness of certain fantasies that
      alter the person's aesthetic sense in such a way that the formal qualities of the
      experience, the shape, texture, and color, appear to become the sources of our
      most disturbing and repulsive feelings. This paper reviews the psychoanalytic
      writings concerning the problem of ugliness and offers a psychoanalytic model of
      this universal phenomenon. Clinical vignettes illustrate key points. The paper
      closes with a discussion of how ugliness can be an opportunity for both the
      analyst and the artist--he or she confronts ugliness, and through the analytic
      and creative process, brings form and perfection to disintegration and disorder.

PMID- 14569667
TI  - Beauty treatment: the aesthetics of the psychoanalytic process.
AB  - Psychoanalysts enjoy doing analysis above and beyond its usefulness to patients;
      one reason for this lies in the aesthetic pleasure the analyst may derive from
      the analytic process. The author discusses this aesthetic pleasure from the
      standpoint of meaning making, communication, love, and professional craft.
      Patients may themselves seek in analysis a certain kind of beauty that is
      normally a byproduct of good enough empathy and communication. Using Kleinian
      theory, the author examines the ways in which destructiveness and aggression may
      be understood in relationship to an aesthetic of psychoanalysis. It is further
      proposed that the aesthetic and ethical principles of psychoanalysis are
      indissolubly linked.

PMID- 14569668
TI  - Catalyzing the dialogue between the body and the mind in a psychotic analysand.
AB  - The author presents the analysis of a 23-year-old, obese, psychotic man who was
      dominated by sensations and unable to work through the different levels of
      psychic elaboration. He could not discriminate between words and concrete objects
      or between the perceptual functions of sense organs and the oral-cannibalistic
      level of instinct. Following the working through of these inabilities, it became
      possible to understand the patient's use of sensation and to make him aware of
      his emotions and conflicts. The author's discussion of this material emphasizes
      the role of the body-mind conflict and how this can be confronted in the analytic
      relationship. Possible links with neuroscience are also indicated.

PMID- 14569669
TI  - Cross-cultural differences in perspectives on the self. Introduction.

PMID- 14569670
TI  - Models of agency: sociocultural diversity in the construction of action.

PMID- 14569671
TI  - Culture and agency: implications for psychological theories of motivation and
      social development.

PMID- 14569672
TI  - An exploration of cultural variation in self-enhancing and self-improving
      motivations.

PMID- 14569673
TI  - Rethinking the value of choice: considering cultural mediators of intrinsic
      motivation.

PMID- 14569674
TI  - Beyond Maslow's culture-bound linear theory: a preliminary statement of the
      double-Y model of basic human needs.
AB  - Maslow's theory of basic human needs is criticized with respect to two of its
      major aspects, unidimensional linearity and cross-cultural validity. To replace
      Maslow's linear theory, a revised Y model is proposed on the base of Y. Yu's
      original Y model. Arranged on the stem of the Y are Maslow's physiological needs
      (excluding sexual needs) and safety needs. Satisfaction of these needs is
      indispensable to genetic survival. On the left arm of the Y are interpersonal and
      belongingness needs, esteem needs, and the self-actualization need. The thoughts
      and behaviors required for the fulfillment of these needs lead to genetic
      expression. Lastly, on the right arm of the Y are sexual needs, childbearing
      needs, and parenting needs. The thoughts and behaviors entailed in the
      satisfaction of these needs result in genetic transmission. I contend that needs
      for genetic survival and transmission are universal and that needs for genetic
      expression are culture-bound. Two major varieties of culture-specific expression
      needs are distinguished for each of the three levels of needs on the left arm of
      the Y model. Collectivistic needs for interpersonal affiliation and
      belongingness, esteem, and self-actualization prevail in collectivist cultures
      like those found in East Asian countries. Individualistic needs are dominant in
      individualist cultures like those in North America and certain European nations.
      I construct two separate Y models, one for people in collectivist cultures and
      the other for those in individualist ones. In the first (the Yc model), the three
      levels of expression needs on the left arm are collectivistic in nature, whereas
      in the second (the Yi model), the three levels of needs on the left arm are
      individualistic in nature. Various forms of the double-Y model are formulated by
      conceptually combining the Yc and Yi models at the cross-cultural, crossgroup,
      and intra-individual levels. Research directions for testing the various aspects
      of the double-Y model are identified for comparisons at these three levels.
      Future studies theoretically guided by the double-Y model will enable us to
      systematically understand, at both aggregate and individual levels, the
      characteristics and interactions of expression and transmission needs, the
      characteristics and interactions of collectivistic and individualistic expression
      needs, and the dynamic processes involved in the transformation of needs from
      collectivistic to individualistic and vice versa under certain specific
      conditions. The double-Y model, as a whole, represents a serious, systematic
      attempt to theoretically and empirically integrate the biological and cultural
      influences on basic motivational states and propensities. Whether this model will
      eventually prove to be able to survive future empirical testing and conceptual
      revision remains to be seen. I must hasten to add, however, that there may be
      other potentially viable models that are worth being advanced in the future for
      accomplishing the same purpose of integrating the biological and cultural
      determinants of the formation, development, and function of human motivation.

PMID- 14569675
TI  - Coherence of culture and generalizability of data: two questionable assumptions
      in cross-cultural psychology.

PMID- 14569676
TI  - [Genetic background of osteoporosis].
AB  - Osteoporosis is characterized by a decrease in bone mass as well as a
      deterioration of the bone architecture resulting in an increased risk of
      fracture. The disease is multifactorial, and it depends on environmental and
      genetic factors. Twin studies have shown that genetic factors account for 60-80%
      of the variance in bone mineral density, the best predictor of the risk of
      osteoporosis. There are different approaches to identify these genetic factors.
      Linkage studies in human and experimental animals have defined multiple loci that
      regulate bone mass but most of the genes responsible for this effect remain to be
      defined. The 11q12-13 locus was the first that was linked to bone mineral density
      of the young female and special bone diseases like high bone mass syndrome and
      osteoporosis-pseudoglioma syndrome. Both diseases appear to be in association
      with LDL receptor-related protein 5 gene mutation. The effect of LDL receptor
      related protein 5 on bone metabolism had not been known only genetic methods
      suggested it. The effect of LRP5 in osteoporosis pathogenesis requires more
      investigation. Association and linkage studies have been performed in order to
      identify candidate genes in the pathogenesis of osteoporosis. Vitamin D receptor
      gene was the first candidate, however its effect is controversial. Other
      candidates, such as insulin like growth factor, interleukin-6, estrogen receptor
      alpha, transforming growth factor beta show no or small effect on bone mineral
      density or fracture frequency. To date only Sp1 polymorphism of collagen gene
      seems to have a consistent effect on bone fragility. The improved understanding
      of osteoporosis genetics should lead to better diagnosis of this disease and new
      treatment and prevention strategies.

PMID- 14569677
TI  - [Numerical chromosome anomalies in human sperm at low sperm concentration].
AB  - INTRODUCTION: With the assisted reproduction techniques the natural selection of
      sperm is bypassed on different levels. AIM: The aim of the present work is to
      determine the frequencies of sperm numerical chromosome aberrations in infertile
      men with low sperm count and to examine the relationship between the spermatogram
      parameters (sperm count and motility) and the aneuploidy and diploidy
      frequencies. METHODS: 32 men with low sperm count were investigated. Semen
      analysis was performed according to the WHO criteria. Disomy and diploidy
      frequencies were detected with fluorescence in situ hibridization using 17, X and
      Y centromeric probes. 200,969 sperm were scored, with the mean of 6272 cells in
      each subjects. The rate of numerical chromosome anomalies were also estimated
      using the detected disomy and the diploidy frequencies. RESULTS: Mean sperm
      concentration of the 32 men was 18.2 million/ml (SD: +/- 8.43, range: 8.0-45.5),
      mean motility 49.4% (+/- 9.32, 30-69.2). The X/Y ratio was 1.07. The mean
      frequencies of sex chromosome disomy, chromosome 17 disomy and diploidy were
      0.36%, 0.16% and 0.56%, respectively. The most frequent disomy was XY disomy
      (0.14). Sex chromosome disomy frequencies were higher in oligospermic samples
      (0.37% vs. 0.32%, OR = 1.18, 95% CI = 1.01-1.39, p < 0.001). With special regard
      to XY disomy (0.08% vs. 0.17%, OR = 1.99, 95% CI = 1.48-2.67, p < 0.001). In
      subjects with oligoasthenozoospermia the diploidy frequency increased (0.96%, OR
      = 2.39, 95% CI = 2.13-2.69, p < 0.001), mostly due to the elevated rate of
      diploid sperm of meiosis II. origin (XX or YY diploids). Estimated frequency of
      the numerical chromosome anomalies was 8.3 +/- 5.3 in the study population.
      Neither the sperm count, nor the sperm motility showed correlation with the
      detected frequency of the chromosome aberrations. CONCLUSIONS: In oligospermic
      patients there is a risk for elevated frequency of sperm with sex chromosome
      aneuploidy, especially the XY disomy. Furthermore, the diploidy frequency is
      increased in oligozooastenospermic samples. Nevertheless, classical parameters of
      semen analysis (sperm count and motility) do not correlate with the frequency of
      numerical chromosomal anomalies. The risk can be determined using fluorescens in
      situ hybridization on sperm.

PMID- 14569678
TI  - [Accreditation of medical laboratories].
AB  - In Hungary, the National Accreditation Body was established by government in 1995
      as an independent, non-profit organization, and has exclusive rights to accredit,
      amongst others, medical laboratories. The National Accreditation Body has two
      Specialist Advisory Committees in the health care sector. One is the Health Care
      Specialist Advisory Committee that accredits certifying bodies, which deal with
      certification of hospitals. The other Specialist Advisory Committee for Medical
      Laboratories is directly involved in accrediting medical laboratory services of
      health care institutions. The Specialist Advisory Committee for Medical
      Laboratories is a multidisciplinary peer review group of experts from all
      disciplines of in vitro diagnostics, i.e. laboratory medicine, microbiology,
      histopathology and blood banking. At present, the only published International
      Standard applicable to laboratories is ISO/IEC 17025:1999. Work has been in
      progress on the official approval of the new ISO 15189 standard, specific to
      medical laboratories. Until the official approval of the International Standard
      ISO 15189, as accreditation standard, the Hungarian National Accreditation Body
      has decided to progress with accreditation by formulating explanatory notes to
      the ISO/IEC 17025:1999 document, using ISO/FDIS 15189:2000, the European EC4
      criteria and CPA (UK) Ltd accreditation standards as guidelines. This harmonized
      guideline provides 'explanations' that facilitate the application of ISO/IEC
      17025:1999 to medical laboratories, and can be used as a checklist for the
      verification of compliance during the onsite assessment of the laboratory. The
      harmonized guideline adapted the process model of ISO 9001:2000 to rearrange the
      main clauses of ISO/IEC 17025:1999. This rearrangement does not only make the
      guideline compliant with ISO 9001:2000 but also improves understanding for those
      working in medical laboratories, and facilitates the training and education of
      laboratory staff. With the official acceptance of ISO 15189 the clauses of this
      harmonized guideline fulfill the requirements of the new international standard
      as well. Accreditation of medical laboratories in Hungary may not only facilitate
      quality improvement of laboratory services, but also the development of a quality
      based purchasing and reimbursement policy of the health insurance fund.

PMID- 14569679
TI  - [Pause-dependent Torsade de Pointes following acute myocardial infarction].
AB  - The authors report an early occurrence (within 48 hours) of the newly described
      form of pause-dependent torsade de pointes following acute myocardial infarction.
      QT prolongtion after myocardial infarction a common ECG finding.
      Postextrasystolic QT prolongation rare but one of the warning signs for torsade
      de pointes ventricular tachycardia following myocardial infarction. Careful
      monitoring is suggested in these cases.

PMID- 14569680
TI  - [Two successful pregnancies after total thyroidectomy and parathyroidectomy].
AB  - A 23-year-old woman presented with a thyroid mass and total thyroidectomy was
      performed. Histological examination revealed papillary thyroid carcinoma. In the
      postoperative period severe hypocalcaemia due to permanent hypoparathyroidism
      developed. After postoperative telecobalt irradiation and substitutional hormone
      therapy (200-400 micrograms/day levothyroxin and 0.5-1.5 micrograms/day
      calcitriol) the patient had two successful pregnancies. The adaptation of the two
      mature newborns was without any complication. During pregnancy, the patient was
      treated with increased doses of levothyroxine and calcitriol. During lactation,
      the hormone substitution doses were decreased to those used in non pregnant
      stage. The authors conclude that the successful pregnancies were largely
      attributable to adequate dose-adjustments of levothyroxine and calcitriol based
      on frequent measurements of thyroid hormones and serum calcium.

PMID- 14569681
TI  - [Treatment of autoimmune hepatitis].

PMID- 14569682
TI  - [Depiction of pathological breasts in the fine arts].

PMID- 14569684
TI  - [Malignant tumors of the colon and rectum].
AB  - The authors present their five year long experience in surgical treatment of
      colorectal cancer at Zvornik Health Center. 77 patients diagnosed with colorectal
      cancer underwent surgery during the five year period (1998-2002). This number
      represented about 2% of the total number of surgeries performed during the same
      time period. 80% of surgical interventions were elective, (82 patients), and 20%
      urgent (35 patients). Standard surgical procedures were applied in determining of
      the anatomical location of the pathological substrate. Aggravating factors in
      successful application of surgical intervention in treatment of colorectal cancer
      are: late diagnosis of colorectal cancer, low level of health education of the
      population, inadequate training of the physicians in primary health care,
      nonexistent national program for early detection of noninfectious diseases. In
      cases where colorectal cancer was diagnosed in an advanced stage, two-stage
      treatment and multi modal approach in combination with chemotherapy were
      treatments of choice. Incidence of colorectal cancer is still on the rise.

PMID- 14569685
TI  - [Incidence of malignancies of the colon treated at the Clinic for Abdominal
      Surgery at the University Clinical Center in Sarajevo in the prewar (1987-1991)
      and postwar (1996-2000) period].
AB  - Malignant tumours are important health problems today. In most countries they are
      second cause of death in general population. In this work it was presented
      epidemiology of rectal cancer which are treated in Abdominal Surgery Department
      at University Clinical Center in Sarajevo of Bosnia and Herzegovina. This is only
      part of complete investigation of incidence malignants in Bosnia and Herzegovina.
      Our study is a retrospective and observation two five years periods. First is
      between 1987.g. and 1991.g., and second is between 1996 and 2001.g. During first
      period in Abdominal Surgery Department, we had 668 cases of abdominal malignant
      and 225 of these cases were carcinoma colorecti. In the second period we had 831
      cases of abdominal malignant and 311 of these cases were carcinoma colorecti.
      When we compared our data with other referents from East Europe, we can say that
      the results mostly the same, and when we compared first five years period (1987
      1991), with second five years period (1996-2001), there are also no statistically
      significant increase.

PMID- 14569686
TI  - [Results of treatment of anorectal diseases over a 2-year period].
AB  - For the success of surgical treatment of anorectal diseases it is necessary to be
      familiar with different surgical methods for solving the problem. After
      examination, a surgeon needs to choose optimal method or a combination of two, in
      order to achieve the best effect. A correct choice of patients suitable for
      outpatient treatment is of extreme importance because enforcement of such
      treatment in patients who are suitable for stationary treatment would compromise
      the method. In this study we have presented the results of outpatient treatment
      of anorectal diseases during a two-year period (2000-2001). During this period we
      have studied 597 cases, out of which 524 patients were successfully treated in an
      outpatient clinic while for 31 patient (5%) we have concluded that they need a
      stationary treatment to which they were sent and in whom malignant tumors were
      found. Methods used in the treatment of different stages of hemorrhoides as being
      the most frequent disease were Barron's elastic ligature, infrared coagulation,
      sclerotherapy, HAL (Hemorrhoidal Artery Ligation), with two methods combined most
      commonly. We achieved excellent or very good results of the treatment in 87% of
      the patients, and only 2 patients had to be sent for surgical treatment. Beside
      hemoorhoides, methods that can be performed in local anesthesia in an outpatient
      institutions can be performed as well in cases of other benign conditions (such
      as lateral sphincterotomy in cases of anal fissure, fistulotomy and similar).
      Therefore, we have successfully solved 88% of the cases in out-patient clinic. An
      increased flow of proetologic lesions that were discovered. During 2-year period,
      we have solved 90% of anorectal diseases by using minimally invasive surgical
      methods. Successful and simple treatment of benign anorectal diseases increases
      the flow of patients having such symptoms, which increases the number of
      discovered malignant tumors.

PMID- 14569687
TI  - [Multivisceral resection in locally advanced carcinoma of the colon and rectum].
AB  - Locally advanced colorectal canter may require an intraoperative decision for the
      block resection of surrounding organs or structures to achieve complete tumour
      removal. This decision must weigh the risk of complications and death of
      multivisceral resection against a potential survival benefit. Little is known
      about the prognostic factors and their influence on the outcome of multivisceral
      resection for colorectal cancer. We demonstrate our experience with multivisceral
      resections for the primary colorectal cancer. Patients undergoing multivisceral
      resection for primary colon or rectal cancer between I-I.2000-I-VII.2003 were
      identified from retrospective database. Multivisceral resection was performed in
      41 of 378 patients with a median age of 61 years. Postoperative rates of
      complications and death in 41 patients were 30.9% and 12.1%. Histologic tumour
      infiltration was shown in 58.3% of patients with curative resection.
      Multivisceral resection is safe, and long-term survival after curative resection
      is similar to that after standard resection. As the palliative resections cannot
      be predicted accurately at the time of surgery, every effort should be made to
      achieve complete tumour resection.

PMID- 14569688
TI  - [Interinnominate abdominal amputation (hemipelvectomy) in treatment of pelvic
      malignancy].
AB  - Cancers of rectum and anus are among most frequent cancers with a tendency of
      increasing frequency. According to available data, the percentage of surgeries
      performed during period 1973-1977 was 61%, and during period 1991-1993 78%. From
      those data it can be seen that the frequency of performed surgical treatments is
      evidently increasing lately. High percentage of patients suffer from the process
      that is involving neighbouring organs and tissues, therefore declared as
      inoperable. In this study we present five cases with malignant tumors of pelvis
      who were treated during period 1990-2002 with mutilating surgical technique-
      chemipelvectomy. In all surgical procedures we have used King's and Steelquist's
      methods. At the same time, these surgical procedures are moving the limits of
      tumors' inoperability. The survival period for 4 patients was over one year, and
      1 patient died due to postoperative embolism. In 1 patient, the wound has healed
      per secundam. We registered no cases of local recurrence. The new possibilities
      in the treatment of pelvic tumors which are often declared as inoperable are
      opened due to the fact that chemipelvectomy is moving the limits of so-called
      inoperable types of tumors. We believe that it is necessary to open new
      discussions on this issue because the coming time will offer new possibilities in
      the surgical treatment of pelvic tumors.

PMID- 14569689
TI  - [Early surgical complications after treatment of malignant diseases of the colon
      and rectum].
AB  - Operations malignity on the colon and rectum belong into a group of risky
      operational treatment, which has a high percentage of early postoperational
      complications in comparison to the other operational treatments in digestive
      surgery. To determine the precentage of the postoperational complication of the
      resectional treatment on the colon and rectum, obtained results compare with the
      experience of the other authors. Analysed 439 patients operated from malignity on
      the colon and rectum in five year period (1998-2002). Bleeding after the
      postoperation had 8 patients (1.82%). Dehiscentio anastomosis has been evident in
      21 patient (4.78%). Interintestinal apscess has been evident in 4 patients
      (0.91%). The infection of operational would of the 45 patients has been (10.25%).
      Dehiscentia of the operational wound of 10 patients has been (2.27%). Ileus in
      early postoperational stage has been evident in 16 patients (3.64%). The Total
      number of reoperation based on the analysed complications has been evident in 50
      patients (11.38%). As e conclusion we can see that ours results coincides with
      the experience of the other authors.

PMID- 14569690
TI  - [Personal experience with unconventional treatment in extraperitoneal injuries of
      the rectum].
AB  - Because of the unannounced war state in Bosnia and Herzegovina in the period 1992
      1995, there were overlapping of war and peaceful doctrine of taking care of all
      injuries. Many extraperitoneal and intraperitoneal injuries of colon and rectum
      were treated in the Cantonal Hospital Zenica and in the other war hospitals where
      the staff of Cantonal Hospital Zenica worked. According to the war doctrine all
      injuries of colon and rectum are treated operatively with obligatory making
      colostoma. This presentation includes 7 cases of extraperitoneal rectum injuries
      from great number of intra- end extraperitoneal injuries of rectum and injuries
      of colon, which were not treated by principles of war doctrine. We emphasize that
      surgical teams were experienced, had diagnostic equipment and operation hall with
      staff and equipment in the case of reintervention. THE AIM: Of this presentation
      is to point out the size of lesion and the association with the other injuries in
      order to decide about operative or conservative way of treatment as alternative
      method. It was necessary to define the patients in which we would avoid colostoma
      with adequate drainage procedures, first of all looking at the size of lesion and
      the association with the other injuries. THE MAIN DIAGNOSTIC PROCEDURE: Was
      rectoscopic verification of all 7 injuries with the presentation of size of
      lesion. THE MAIN METHOD OF TREATMENT: Was high grade quality, continuous and
      adequate toilette and drainage of canal of injury and perirectal area following
      with antibiotics (metronidasol) and stool regulation. In comparison with
      doctrinal treatment by making colostoma there was no significant more
      complications and lethal outcome by this alternative method of treatment.
      CONCLUSION: Six of seven cases of extraperitoneal rectum injuries with lesion not
      bigger than 30 mm and with small pelvis mutilation were solved using conservative
      method (not making colostoma).

PMID- 14569691
TI  - [Anatomy of the colon, rectum and anus].
AB  - Deduction of operation, holds in colorectal surgery, include good knowledge of
      anatomy and her connection in that area. Large bowel has special anatomy and
      functional mark. Intensive study of colorectal cancer bring about a new knowledge
      about anatomy of the large bowel, especially about vascular variations. We
      described the very importance characteristic of colon, rectum and anus in this
      article.

PMID- 14569692
TI  - [Principles of surgical treatment of pelvic injuries in polytrauma].
AB  - Involved in polytrauma pelvis girdle's injuries have the high percent of
      mortality. The author in this paper shows importance in time clinical detection
      and treatment after properly classification. It is presented same actual
      classifications of pelvis girdle's injuries. These classifications are based on
      consensus and experience American and European referral centers for pelvic
      girdle's injuries. Their application is imperative for each surgical staff
      included in treatment of polytraumatized patients.

PMID- 14569693
TI  - [Malignant tumor of the large intestine in the advanced stage].
AB  - Increase incidence of the colorectal carcinoma is presented in the highly
      developed countries. The incidence of the disease has been doubled every ten
      years after the age of 40th. The aim of the work is to show an instructive case
      review carcinoma coloascendens an a move progress. The patient 1941, has been
      radically operated in addition of a bad condition. DIAGNOSIS: Carcinoma cacci et
      colonis ascendentis cum metastasibus lymphonody regionalis (Dukes C). Penetratio
      tumoris retroperitonealis et infiltratio capsule renis dex. Polypsis colonis. Op.
      Colectomia cum ilcorectoanastomosis. The postoperative course had been regular.
      The chances to survive five ears are below 30 percent. The case that we present
      is very instructive, because it shows a move progressed phase, a way of treatment
      that is much difficult and expensive with a worse prognosis, than in the cases
      when a carcinoma has been found out in earlier phase.

PMID- 14569694
TI  - [Cecal prolapse after appendectomy].
AB  - Patient N.N. is received to surgery department Canton Hospital "dr Irfan
      Ljubijankic" Bihac, because operative procedures of prolapsa cecuma with terminal
      ileum part and proximal colon input part past appendectomy of performed appendix
      of peritonitis four years ago and the patient didn't get in touch to controlling
      review. The patient is treated by the way of relaparatomy that is delivered
      cranial-caudal with primary closing of cecum with cecostomy that is impulsive
      closed. The way that we access to treatment is correct and good because it is
      made instential passing and the postoperative flow is ordinary, the common
      patient's stand and the cosmetician look is good and satisficially with further
      quality living.

PMID- 14569695
TI  - Traumatic perforation: blast injury.

PMID- 14569696
TI  - Endoscopic views of choanal stenosis in secondary atrophic rhinitis.

PMID- 14569697
TI  - Interarytenoid mucosal bridges complicating endotracheal intubation.

PMID- 14569698
TI  - Plasmacytoma of the petrous temporal bone.

PMID- 14569699
TI  - Electronystagmography: vestibular findings in a patient with tinnitus.

PMID- 14569700
TI  - Proper use of CPT code modifiers.

PMID- 14569701
TI  - Black thyroid.

PMID- 14569702
TI  - Esophageal foreign body.

PMID- 14569703
TI  - Pressure-Specifying Sensory Device: quantitative sensory measurement in the oral
      cavity and oropharynx of normal adults.
AB  - We conducted a study to quantitatively determine the pressure perception
      thresholds in the oral cavity and oropharynx of a normal population with the
      Pressure-Specifying Sensory Device (PSSD). The PSSD measured pressure perception
      thresholds for both static and moving one- and two-point discrimination
      modalities at a variety of sites in the oral cavity and oropharynx as well as in
      the forearm of 11 adults. We also evaluated the ability of the PSSD to enhance
      sensory discrimination in four of these subjects by the process of sensory re
      education for 11 days over a 15-day period. We found that the buccal mucosa and
      the tongue tip were the most sensitive sites in the oral cavity and oropharynx
      and that the floor of the mouth and the soft palate were the least sensitive.
      Sensory discrimination in the oral cavity was enhanced in all four subjects who
      underwent sensory re-education, although it returned to baseline levels over time
      after re-education was discontinued. The degree of intra- and intertester
      variability was minimal. Our data can be used as an aid in the development of
      techniques to surgically restore sensation in the oral cavity and oropharynx.

PMID- 14569704
TI  - Pigmented villonodular synovitis of the temporomandibular joint: a report of two
      cases.
AB  - Pigmented villonodular synovitis is a benign but locally destructive disease that
      originates in the synovial membranes of the joints. It is a proliferative
      disorder of unknown etiology, and it is usually monarthric. Approximately 80% of
      cases involve the knee; the hip, ankle, foot, hand, elbow, and shoulder account
      for most other cases. Pigmented villonodular synovitis in the temporomandibular
      joint is rare. When it does occur, its features include preauricular swelling,
      trismus, and symptoms of temporomandibular joint dysfunction. It can be diagnosed
      by a combination of the history, clinical examination, characteristic radiologic
      findings, and fine-needle aspiration or biopsy results. Wide local excision,
      including the involved bone, and a total synovectomy are advocated because the
      lesion can recur if it is not adequately excised. We report two new cases of
      pigmented villonodular synovitis of the temporomandibular joint, and we review
      the literature on this subject.

PMID- 14569705
TI  - Oncocytic carcinoma of the parotid gland: report of a new case.
AB  - Prior to 2003, only 39 cases of oncocytic carcinoma of salivary gland origin had
      been reported in the English-language literature. We report a new case, which
      occurred in a 48-year-old woman whose disease had metastasized to regional lymph
      nodes. She was treated by radical parotidectomy, with sacrifice of the facial
      nerve, and radical neck dissection. At the 3-year follow-up, she remained free of
      disease. Our review of the literature suggests that patients with such tumors who
      undergo aggressive surgery rather than conservative treatment have the best
      prognosis.

PMID- 14569706
TI  - A different type of 'glue ear': report of an unusual case of prominent ears.
AB  - Prominent ears is a condition that can cause extreme psychological distress in
      young people. This cosmetic deformity can be corrected by otoplasty, an
      outpatient surgical procedure that is associated with a high rate of patient
      satisfaction. We report the unusual case of a teenage boy who had repeatedly
      applied cyanoacrylate adhesive ("superglue") to his postauricular skin in an
      attempt to pin back his prominent ears. This case of "glue ear" was ultimately
      resolved by successful otoplasty, although the residual effects of the glue
      resulted in delayed healing of the surgical wound.

PMID- 14569708
TI  - Tongue viability after bilateral lingual artery ligation and surgery for
      recurrent tongue-base cancer.
AB  - A 73-year-old man came to us with a second primary tumor of the tongue base. He
      had undergone a total laryngectomy, neck dissections, and radiation for squamous
      cell carcinoma of the glottis 25 years earlier. Surgery was performed, including
      a subtotal tongue-base resection and pectoralis myocutaneous flap reconstruction.
      Intraoperative findings confirmed tumor involvement of the left lingual artery
      and hypoglossal nerve, both of which were sacrificed. Dissection revealed an
      intact but apparently thrombosed right lingual artery, and this was verified by
      intraoperative Doppler evaluation. Postoperatively, the preserved oral tongue
      remained well perfused and viable, and tongue mobility was good. In patients who
      have undergone previous head and neck cancer resections, collateral blood supply
      to the tongue might develop if the flow of one or both of the lingual arteries is
      interrupted. This possibility can be fully evaluated by preoperative angiography,
      which might offer these patients the potential for tongue preservation.

PMID- 14569707
TI  - Phylogeny and embryology of the facial nerve and related structures. Part I:
      Phylogeny.
AB  - The study of evolution provides invaluable insights into human structure and
      function. Much of evolution is recapitulated during human gestation.
      Understanding the evolutionary process helps clarify seemingly complex embryology
      and anatomy, such as that of the facial nerve and related ear structures, as well
      as the anomalies that occur when human development is interrupted.

PMID- 14569709
TI  - Juvenile xanthogranuloma: a rare cause of subglottic cyst and stenosis.
AB  - Only two cases of juvenile xanthogranuloma of the larynx have been previously
      reported in the literature. We report a new case, which occurred in an 18-month
      old girl. The patient was brought to us for treatment of stridor and respiratory
      distress. During examination, she was found to have a subglottic mass. The lesion
      was treated with laser microlaryngoscopy, which relieved the patient's
      respiratory distress and obviated the need for tracheotomy. Pathologic
      examination of the mass revealed that it was consistent with a juvenile
      xanthogranuloma. Juvenile xanthogranuloma is generally a benign and self-limiting
      disease, but complications can occur when the space that the tumor occupies
      causes functional impairment.

PMID- 14569710
TI  - Pneumococcal bacteremia with retropharyngeal soft-tissue inflammation and acute
      epiglottitis.
AB  - Pneumococcal bacteremia secondary to acute epiglottitis is relatively rare, and
      all previously reported cases occurred in immunocompromised patients. We report a
      case of pneumococcal bacteremia associated with acute epiglottitis and
      retropharyngeal soft-tissue inflammation with upper airway narrowing that
      occurred in an otherwise healthy patient. In light of our unique finding, we
      recommend that pneumococcal bacteremia be suspected in an otherwise healthy
      patient who has systemic manifestations associated with acute epiglottitis.

PMID- 14569711
TI  - Yellow fever vaccine. WHO position paper.

PMID- 14569712
TI  - Foodborne diseases in Malaysia.

PMID- 14569713
TI  - Knowledge, attitudes and beliefs related to HIV/AIDS among adolescents in
      Malaysia.
AB  - Findings on knowledge, attitudes and beliefs related to HIV/AIDS among 520
      Malaysian adolescents, aged 15 to 21 years, based on a survey conducted in
      Peninsular Malaysia showed that the average score for knowledge on HIV/AIDS was
      high, and majority showed a positive attitude towards the disease. However,
      misconceptions regarding transmission and gender bias related to sexual behaviour
      and contracting the disease prevailed. Although 72 percent of the sexually
      experienced did not use protection at first sexual intercourse, 80 percent did
      not perceive themselves to be at risk of contracting HIV/AIDS. A critical review
      of existing HIV/AIDS prevention programmes to focus on adolescent risk-taking
      behaviour and sexuality issues, including male-female negotiation skills, is
      warranted.

PMID- 14569714
TI  - Bacterial enteropathogens isolated in childhood diarrhoea in Kuala Lumpur--the
      changing trend.
AB  - A retrospective review of all stool samples obtained from children aged < 16
      years with diarrhoea from University of Malaya Medical Centre (UMMC), Kuala
      Lumpur, from 1978 to 1997 was undertaken to ascertain the pattern of bacterial
      pathogens causing diarrhoea in children in an urban area in Malaysia. Of 26444
      stool samples processed, 2989 (11%) were positive. The five most common bacterial
      pathogens isolated were non-typhoidal Salmonella (57%), enteropathogenic E. coli
      (EPEC) (14%), Shigella spp. (11%), Campylobacter spp. (5%) and Aeromonas spp.
      (4%). There was a significant reduction in the average percentage of positive
      isolation during the last 5 years of the study period as compared to the first 5
      years (15.0% vs. 7.2%; r = -0.92, p = 0.0001). EPEC and Shigella spp. were less
      commonly isolated in the last five years compared with the first five years of
      the study (6% vs 21% p < 0.001 for E. coli; 7% vs 22%, p < 0.001 for Shigella
      spp.). This information is important for public health education in reducing the
      incidence of childhood diarrhoea further, and in the selection of appropriate
      antimicrobials in the management of extra-intestinal complications of childhood
      diarrhoea.

PMID- 14569715
TI  - Postal surveys: a review of articles published in the Medical Journal of Malaysia
      between 1991-2000.
AB  - Postal surveys are becoming an increasingly popular method of conducting research
      in Malaysia. However, the response rates from these surveys have not been well
      studied. All postal surveys published in the Medical Journal of Malaysia between
      1991-2000 were therefore reviewed to provide an overview of the response rates
      that may be expected, and to assess if this is a valid method of conducting
      research here. The response rates of postal surveys ranged from 30-87.5%. Seven
      of 13 postal surveys (54%) had a response rate of less than 50% and only 2 of 13
      (15.4%) had a response rate of more than 70%, raising doubts on the use of postal
      surveys as a research tool.

PMID- 14569716
TI  - Food security and child nutritional status among Orang Asli (Temuan) households
      in Hulu Langat, Selangor.
AB  - This study was conducted to determine the prevalence of household food insecurity
      and its potential risk factors and outcomes among the Orang Asli (Temuan)
      households. Socioeconomic, demographic and food security information of the
      households and anthropometric measurements and dietary intakes of preschoolers (n
      = 64) were obtained using a structured questionnaire. Food security was assessed
      using the Radimer/Cornell hunger and food insecurity instrument. Diet quality was
      based on 24 hour recall and analyzed according to the Malaysian RDA and Food
      Guide Pyramid. Majority of the households (82%) reported some kind of household
      food insecurity. The prevalence of significant underweight, stunting and wasting
      were 45.3%, 51.6% and 7.8%, respectively. Dietary intakes were less than 2/3 RDA
      levels for calories, calcium and iron. However, the intakes of protein, vitamin
      A, vitamin C and niacin exceeded the RDA and the sources for these nutrients were
      mainly rice, fish and green leafy vegetables. Among the five food groups, only
      the number of servings from cereals/cereal products/tubers group was achieved
      while that of the milk/diary products was the worst. Majority of the children
      (68.7%) had poor, 31.3% had fair and none with excellent diet quality. In
      general, diet quality and nutritional status of the children decreased as
      household food insecurity worsened. It is recommended that the nutritional
      problems of Orang Asli children be addressed through health, nutrition and
      economic programs and further studies should be carried out on determinants and
      consequences of household food insecurity.

PMID- 14569717
TI  - After-hour home care service provided by a hospice in Singapore.
AB  - A home care Hospice programme was set up to provide care to the patients with
      advanced diseases and their families in Singapore. After office-hour, the service
      is managed by a doctor on weekdays, with the assistance of a nurse during daytime
      on Saturdays, Sundays and public holidays. The doctor on-call made an average of
      3.1 phone calls and 1.3 visits each weekday evening. Over the weekends and public
      holidays, there were a mean of 16.7 phone calls and 6 visits each day. More than
      half of the visits (50.3%) were made for certification of death. The commonest
      symptoms that prompted visits were dyspnoea (20%) and pain (12.2%). The busiest
      period during weekdays was between 6.00 pm and 11.00 pm, when our doctors did
      most of their visits. The workload of the hospice home care service is likely to
      increase and resources such as family health physicians can be explored to help
      to meet this increasing demand. This can be achieved through the provision of
      comprehensive training and easy accessibility to medical records which are kept
      with patients.

PMID- 14569718
TI  - Primary biliary cirrhosis at Hospital Kuala Lumpur: a study of 17 cases seen
      between 1992 and 1999.
AB  - A prospective descriptive study of Primary Biliary Cirrhosis at Hospital Kuala
      Lumpur was undertaken from January 1992 to December 1999. A total of 17 patients
      were seen with a female to male ratio of 3.25:1. The mean age at presentation was
      45.9 years (range: 14 years to 67 years) with a mean follow-up of 33.4 months
      (range: 3 months to 95 months). Fatigue was the most common clinical symptom at
      presentation. Alanine transaminase and alkaline phosphatase levels were elevated
      in 93% of patients at presentation. The antimitochondrial antibody was positive
      in 87% of patients. Ursodeoxycholic acid therapy resulted in significant
      symptomatic relief and biochemical improvement in all those who were treated.

PMID- 14569719
TI  - Clinical profile of acute flaccid paralysis.
AB  - This study was done to determine the clinical course, cause and outcome of Acute
      Flaccid Paralysis (AFP) in children. All AFP cases (< 15 years) in the children's
      ward of Khulna Medical College Hospital (Bangladesh) were recorded, investigated
      and followed up to sixty days as a part of passive surveillance. Main outcome
      variables were vulnerable age group, vaccine status, predominant limb
      involvement, clinical variants, virus isolation and residual paralysis. Thirty
      four children with AFP were admitted in hospital in the last three years with the
      highest number (14) in 1998. The majority of children belonged to the age group 5
      9 years with a male female ratio of 1.3:1. Nearly one third of the cases were
      either partially vaccinated or not vaccinated at all. The lower limbs bore the
      brunt of paralysis excepting a few (14.7%). Clinically, Guillain Barre Syndrome
      was the commonest (47.1%) followed by encephalomyelitis. No poliovirus was
      isolated from these cases. Residual paralysis was observed in four out of ten
      cases who returned for follow up. AFP will continue to occur even after
      eradication of poliomyelitis and Guillain Barre Syndrome is the most important
      clinical entity for this.

PMID- 14569720
TI  - Thoracoscopic sympathectomy for primary palmar hyperhydrosis: the Penang Hospital
      experience.
AB  - BACKGROUND: Primary palmar hyperhidrosis is a functionally and socially disabling
      condition. The choice of treatment is controversial. OBJECTIVE: To examine the
      clinical presentation of primary palmar hyperhidrosis and the results of
      treatment with thoracoscopic sympathectomy in a local setting. MATERIALS AND
      METHODS: A retrospective study of 7 patients involving 10 sympathectomies between
      October 1997 and October 2000 was undertaken. RESULTS: The duration of
      anaesthesia ranged from 55 to 130 minutes with the majority being 1 hour. The
      immediate results were good, with all operated limbs dry soon after operation.
      There was no mortality or serious morbidity in this study. All were satisfied
      with the results of surgery. CONCLUSIONS: Primary palmar hyperhidrosis is not
      uncommon but rather underdiagnosed. Thoracoscopic sympathectomy is an effective
      treatment with minimal complications.

PMID- 14569722
TI  - A retrospective review of mucocutaneous infections by human herpesvirus 1 and 2
      in an urban population in Malaysia.
AB  - This is a 10-year retrospective review of mucocutaneous infection by human
      herpesvirus 1 (HHV1) and human herpesvirus 2 (HHV2) carried out by the virus
      diagnostic unit of University Malaya Medical Centre (UMMC). A total of 504
      specimens from UMMC and a private clinic in the same city (KLSC) were tested; 198
      samples from patients with oral lesions and 306 from patients with genital
      lesions. HHV1 was found to be responsible for 98.4% of oral lesions whereas HHV2
      was the cause of 83.6% of all genital lesions. Detailed analysis showed no
      statistical difference by age group, race or gender among the patients with oral
      and genital lesions. Two laboratory methods were used in this study. Of the total
      504 specimens tested, 18.0% specimens were positive by direct immunofluorescence
      (IF), 55.0% by virus isolation and 56.5% when both methods were used in
      combination. Although IF can provide a more rapid diagnosis, it is, however, less
      sensitive and can be attributed partly to inadequate collection of specimens.

PMID- 14569721
TI  - Review of the trends and causes of food borne outbreaks in Malaysia from 1988 to
      1997.
AB  - This paper examines the trend and possible contributing factors for the
      occurrence of the food borne diseases outbreaks in Malaysia. These diseases
      mainly are cholera, typhoid fever, hepatitis A, dysentery and food poisoning. The
      outbreaks still occur sporadically in certain high risk areas throughout the
      country. The incidence rate of all the other three major food borne diseases
      steadily declined from the year 1988 to 1997 except for food poisoning and
      cholera. Statistic of food poisoning from the year 1996 to 1997 showed that 66.5%
      of the outbreak occurred in schools whereas only 0.4% originated from the
      contaminated food sold at various public food outlets. The school age group is
      always more affected than the general population. Amongst the contributing
      factors identified are related to unhygienic food handling practices followed by
      inadequate safe water supply and poor environmental sanitation. A multisectoral
      approach between Ministry of Health and other government agencies or private
      agents needs to be undertaken in the management of the food borne diseases in
      order to curb the incidences of food borne diseases in Malaysia.

PMID- 14569723
TI  - Hand, foot and mouth disease: University Malaya Medical Centre experience.
AB  - The prevalence of HFMD as well as the causative agents was unknown in peninsular
      Malaysia prior to May 1997. From May 1997 to June 2001, 585 patients suspected to
      have enterovirus infections, with 467 patients clinically diagnosed as having
      HFMD, were investigated in the diagnostic virology unit of the University Malaya
      Medical Centre. Data from this study showed that HFMD is endemic in Malaysia with
      the occurrence of two outbreaks during the study period. In each outbreak, a
      number of viruses were isolated but enterovirus 71 was the main virus isolated in
      both outbreaks. Echovirus 7 (Eo7) was isolated from 5 patients with HFMD in the
      second outbreak, a clinical entity that has not been attributed to it previously.
      Children aged 4 years and below, particularly those between 1 and 2 years of age,
      were in the main group of patients affected by the illness. HFMD by itself and
      without neurological involvement was relatively benign and self-limiting. There
      was no significant difference in the virus isolation rate with respect to gender
      and ethnic groups. Virus isolation was attempted in a total of 764 clinical
      specimens consisting of 342 stool specimens, 285 oral secretions specimens and
      137 vesicular fluid specimens. Oral specimens gave the highest virus isolation
      rate (33.3%) followed by vesicular specimens (27.0%). Stool specimens only
      yielded an isolation rate of 14.0%.

PMID- 14569724
TI  - Jaundice clearance and cholangitis in the first year following portoenterostomy
      for biliary atresia.
AB  - Sixty-one patients with biliary atresia, who underwent portoenterostomy (PE)
      between 1992 to 1998 in the Institute of Pediatrics, Kuala Lumpur and were
      followed for a period of one year, were studied to analyze the factors associated
      with jaundice clearance and cholangitis following PE. Sex distribution was equal.
      Majority of patients were Malays. Mean age in days at admission to the surgical
      ward was 66.90 +/- 23.36 and mean age at PE was 75.85 +/- 24.05. At the end of
      one-year follow-up, six patients (10%) had died, 35 (57%) developed one or more
      attacks of cholangitis, 35 (57%) had portal hypertension, eight (13%) liver
      failure and six patients had esophageal variceal bleeding. Thirty-three patients
      (54%) had jaundice clearance with a mean clearance time of 85 days after PE. The
      study shows that when the ductules in the porta hepatis were < 150 mu in size,
      persistence of jaundice after PE and the incidence of cholangitis in the first
      post-operative year were higher; patients with cholangitis in the first year had
      lower rate of jaundice clearance. Jaundice clearance was achieved in more
      patients when their postnatal age at the time of PE was lower but the
      relationship was not linear. Age at PE also did not have a linear temporal
      relationship to the incidence of cholangitis and the size of portal ductules.
      Prospective, multi-center based local studies on a bigger patient population are
      needed to identify other indicators of successful outcome following PE. This
      would help to define the indications for primary liver transplantation in the
      local population.

PMID- 14569725
TI  - Seroprevalence of human parvovirus B19 infection in an urban population in
      Malaysia.
AB  - A seroepidemiological study carried out on 800 stored serum samples collected
      between January 1999 to December 2000 derived from an urban population in
      Malaysia showed that the overall seropositive rate of human paravovirus B19
      infection was 37.6%, with an overall geometric mean titre (GMT) of 18.3 IU. The
      seropositive rates of B19 among the male and female populations were 39.0% and
      36.3% respectively. The seropositive rates among the racial groups were 37.2%,
      38.2%, 38.1% and 29.4% respectively for the Malays, Chinese, Indians and other
      races. There was no statistical significant gender and racial differences in the
      B19 seropositive rates. When compared with the seroprevalence of B19 infection in
      other Asian countries, the seropositive rate of B19 in Malaysia was low in the
      younger age group and increased steadily with age. The unusual finding in this
      study was the presence of a high seropositive rate in those between six months to
      five years of age, especially in children in the one year old age group.

PMID- 14569726
TI  - Cervical necrotising fasciitis consequent to mastoid infection.
AB  - We present a case of cervical necrotising fasciitis in a 56 year old man,
      secondary to a rare mastoid infection. The patient had coexisting diabetes
      mellitus and hypertension. He was treated with early surgical debridement
      followed by neck and chest reconstruction and radical mastoidectomy. Aggressive
      antibiotic therapy and supportive care was given. He recovered well with minimal
      residual functional deficit.

PMID- 14569727
TI  - Day care percutaneous renal surgery--is this viable?
AB  - Pros and cons of Percutaneous Nephrolithotripsy (PCNL) versus Extracorporeal
      Shockwave Lithotripsy (ESWL) have often been highlighted when one discusses on
      the management of renal stones. An oft quoted point is that PCNL entails a
      prolonged hospital stay whereas ESWL sessions are day surgical in nature.
      However, PCNL has superior stone clearance rate as compared to ESWL especially
      for lower pole stones. In addition, PCNL is more suitable for large bulk stones
      and when ancillary procedures are required e.g. endopyelotomy. The first 50 cases
      of successful tubeless PCNL were reported by Bellman et al in 1997. The
      remarkable recovery of patients in their series encouraged them to employ this
      technique as their technique of choice for the majority of their cases. A similar
      technique was employed on endopyelotomy by Liang et al and they concluded that
      this was a safe, less morbid and effective technique. We report our first case of
      tubeless PCNL.

PMID- 14569728
TI  - Multiple bilateral cannon-ball lung metastases from carcinoma of the prostate:
      orchiedectomy induced remission.
AB  - A 56-year-old man presented with lower urinary tract obstructive symptoms,
      hemoptysis and progressive dyspnoea. Digital rectal examination showed an
      enlarged nodular prostate and a tru-cut biopsy confirmed carcinoma prostate.
      Chest x-ray showed multiple bilateral cannon ball opacities suggestive of
      metastases. He underwent bilateral orchidectomy and follow up assessment showed
      significant clearing of the cannon-ball lesions in the lungs. He remained
      asymptomatic at follow up that has extended to 8 years.

PMID- 14569729
TI  - A rare case of bleeding in a cerebellopontine angle epidermoid cyst.
AB  - Epidermoid cysts of the central nervous system are described as rare, benign,
      slow growing lesions with a history of high rate of recurrence even after
      surgical removal. This lesion is rarely located at the cerebellopontine angle and
      is found to be composed of solid and cystic components with close adherence to
      vital neurovascular structures that might complicate its removal. We present a
      rare case of a twenty-five year old housewife with signs and symptoms of
      increased intracranial pressure due to the above pathology after multiple
      episodes of intra-tumoral bleeding. Microneurosurgical techniques were used for
      tumour dissection and excision. The patient recovered well after a three-year
      follow-up. This is the fourth example in the index medicus of bleeding seen in a
      histopathologically proven cerebellopontine angle intraepidermoid cyst.

PMID- 14569730
TI  - Non-sporulating Chrysosporium: an opportunistic fungal infection in a neutropenic
      patient.
AB  - We report a case of an invasive infection with non-sporulating Chrysosporium
      species in a patient who was treated with chemotherapy for relapsed acute
      lymphoblastic leukemia. This patient presented with a persistent lobar pneumonia,
      skin lesions, and possible involvement of the central nervous system. The patient
      responded to treatment with amphotericin B and oral itraconazole.

PMID- 14569731
TI  - Appendicitis following blunt abdominal trauma.
AB  - A young boy presented with history of abdominal trauma. History and initial
      clinical findings suggested a soft tissue injury. Due to increasing abdominal
      pain and fever, we proceeded with an exploratory laparotomy with a diagnosis of
      intra-abdominal injury, at which we found a perforated appendix. Appendicitis
      following blunt abdominal trauma needs high index of suspicion.

PMID- 14569732
TI  - Pseudocyst of adrenal gland.
AB  - Cysts of the adrenal gland are uncommon. We report a case of symptomatic
      pseudocyst of adrenal gland in an adult male, which was excised through
      retropertoneoscopic route. Surgery was uneventful and patient returned to pre
      operative activity within seven days of operation. At ten months of follow up
      patient is asymptomatic and doing well.

PMID- 14569733
TI  - Current trends in the management of schizophrenia.
AB  - Schizophrenia is a common and devastating illness. Patients with schizophrenia
      may develop many disabilities both due to the disease process as well as due to
      side effects of the medication used. There are many advances in the treatment of
      schizophrenia, which can effectively reduce many of these disabilities. Treatment
      of schizophrenia is a primary health care responsibility and thus all health care
      personnel need to equip themselves with the latest knowledge on management
      issues. This article outlines the current management issues in schizophrenia.

PMID- 14569734
TI  - Antibiotic resistance in the community.

PMID- 14569735
TI  - Upper respiratory tract infections: to what extent is the management evidence
      based?
AB  - Over a 2-week period, the management of upper respiratory tract infection by 24
      medical officers and medical assistants in Seremban District was studied. Each
      practitioner recorded clinical data and prescription for twenty consecutive
      patients using a structured questionnaire. The extent to which the practitioners
      used "predictive features" (fever, absence of cough, cervical adenopathy,
      enlarged tonsils and exudates on tonsils) in clinical decision-making was
      analysed. The mean antibiotic prescription rate was 28.7% (95% CI: 24.6%, 33.0%).
      The antibiotic prescription rate of medical officers and medical assistants were
      similar. Five features were independently associated with antibiotic prescription
      (phlegm, fever, cervical adenopathy, red throat and tonsillar exudates).
      Antibiotics were prescribed for 22.1% of patients with 0-1 predictive features.
      High prescribers were 5 times more likely to prescribe antibiotics in this group
      of patients than low prescribers. To a large extent the clinical decision-making
      of practitioners in this study was evidence based. However, they were unduly
      influenced by purulent manifestation (phlegm) and redness of throat. The
      antibiotic prescription rate in these government health clinics is potentially
      reducible by means of educational intervention.

PMID- 14569736
TI  - A review of the acute pain service in Hospital Kuala Lumpur.
AB  - This study is a review of the Acute Pain Service in Hospital Kuala Lumpur for the
      years 1998 to 2001. 5042 records from post-operative patients were analysed. The
      majority of patients (81.8%) had satisfactory pain control. Eighty-two percent of
      patients experienced only mild pain at rest on the first post-operative day. The
      highest pain score occurred on the first day in 68.3% of patients. Nausea or
      vomiting occurred in 23.2% of the patients. Eight patients had respiratory
      depression. The low pain scores recorded by most patients and the low incidence
      of side effects reflect the efficiency of the service provided.

PMID- 14569737
TI  - Petrosal sinus sampling in the diagnosis of Cushing's syndrome: preliminary
      experience in University of Malaya Medical Centre.
AB  - Differentiating between Cushing's disease of pituitary origin and ectopic ACTH
      syndrome of extra-pituitary origin remains a major challenge to the clinician
      because of limitations in the diagnostic accuracy of the high-dose dexamethasone
      suppression test. Routine use of inferior petrosal sinus sampling (IPSS) is
      therefore advocated by some authors for these patients. We present our
      preliminary experience of IPSS in 7 consecutive patients with Cushing's disease
      and discuss how the results impacted on the patients' management.

PMID- 14569738
TI  - Inhibition of progesterone secretion by oestradiol administered in the luteal
      phase of assisted conception cycles.
AB  - A prospective randomised study was done to assess the effect of supplemental
      oestradiol in addition to progesterone on the luteal steroid profiles and
      pregnancy outcome in stimulated cycles with and without pituitary down
      regulation. Women undergoing stimulated cycle IVF with GnRH-a and FSH (Group A, n
      = 63) or stimulated intrauterine insemination using CC and FSH (Group B, n = 55)
      were studied. These subjects were randomly allocated to receive either 400 mg
      daily of vaginally administrated Cyclogest (progesterone) alone or in combination
      with 2 mg daily of oral Oestradiol Valerate (E2V) during the luteal phase.
      Significant lower concentrations of plasma progesterone were observed in those
      subjects supplemented with both E2V and progesterone compared to those in whom
      progesterone only was given during the luteal phase (P < 0.05). Exogenous E2V had
      a minimal impact on plasma oestradiol concentrations and did not disguise the
      characterised mid luteal decline in oestradiol secretion. The suppressive effect
      of E2V on plasma progesterone was lost if implantation occurred normally because
      any small change in steroid concentrations was reversed by the rapidly increasing
      concentrations of HCG. Similar pregnancy rates were observed among subjects
      supplemented with or without oestradiol. The addition of oestradiol to the luteal
      supplement suppresses endogenous corpus luteum progesterone secretion
      irrespective of the type of assisted conception cycle and that its use is
      unlikely to be beneficial to the process of implantation.

PMID- 14569739
TI  - Nasal and nasal-type natural killer (NK)/T-cell lymphoma: immunophenotype and
      Epstein-Barr virus (EBV) association.
AB  - Epstein-Barr virus (EBV) is believed to have a pathogenic role in lymphomas of
      the upper-aerodigestive tract. This study aims to elucidate the virus association
      pattern in nasal and nasal-type NK/T-cell lymphomas, and in sequential biopsies
      of these tumours. A total of 31 cases of previously diagnosed as lethal midline
      granuloma. Stewart's granuloma, nasal T-cell non-Hodgkin's lymphoma (T-NHL) and
      NK/T-cell lymphomas from all anatomical sites were retrieved from the files for
      the study. Reviews of these cases confirm 8 nasal T-NHL, 19 nasal and 4
      extranasal lymphomas of NK/T-cell phenotype from 10 Malays, 18 Chinese, 2 Indian
      and 1 Kadazan. The male: female ratio was 2.4: 1. All T- and NK/T-cell lymphomas
      strongly expressed TIA-1 and 63% expressed CD2. The majority of NK/T-cell
      lymphoma occurred in Chinese (13/23), of which 12/13 (92%) of these cases were
      associated with EBV. Of the 15 nasal and 9 tonsillar B-cell lymphomas included
      for a comparison study, only 3 (20%) of the nasal cases were associated with EBV
      (1 male Chinese, 1 female Chinese and 1 male of other ethnic group). Eight cases
      of NK/T-cell tumours with sequential biopsies show persistence of EBV,
      irrespective of the interval and sites of subsequent presentations. This study
      confirms the cytotoxic nature of NK/T-cell tumour and that EBV is strongly
      associated with the disease regardless of the anatomical site of presentation and
      ethnicity. However, nasal and paranasal lymphomas of all phenotypes appear to
      show higher predilection of EBV association in the ethnic Chinese when compared
      to non-Chinese.

PMID- 14569740
TI  - Knowledge and practice of medical doctors on chronic obstructive pulmonary
      disease: a preliminary survey from a state hospital.
AB  - This study was done to ascertain the knowledge and practice of medical officers
      on spirometry and management of COPD in a medical department of a state hospital.
      A total of 81 questionnaires with nine items were distributed to medical officers
      in the medical department (MD) and in other departments (controls). Eight
      incomplete questionnaires were rejected. In all 15 (21%) respondents were
      analysed from MD and 58 (79%) from the control group. The respondents from MD
      were aware that spirometry was important in COPD (100% versus 69%, P < 0.01) but
      in practice both groups were as likely to use peak expiratory flow rate.
      Respondents from MD were more likely to treat mild COPD (73% versus 12%, P <
      0.001) according to Malaysian Thoracic Society COPD guidelines and also more
      likely to perform steroid trial (93% versus 37%, P < 0.001). Only 9 (60%) from MD
      and 33(57%) would refer patients for home oxygen assessment. This preliminary
      survey suggests that there was lack of translation of knowledge into practice
      particularly in terms of use of spirometry in COPD as well as lack of awareness
      for home oxygen assessment. A bigger survey involving all doctors in the state to
      answer issues raised in this preliminary survey is being conducted.

PMID- 14569742
TI  - Husband-wife communication and family planning practices among Malay married
      couples in Mukim Rusila, Terengganu.
AB  - The role of husband-wife communication in the practice of family planning was
      studied among the rural Malay couples in Mukim Rusila, Terengganu. It was a cross
      sectional study in which a cluster sampling was used to select the study sample.
      A total of 193 (100.0%) wives and 74 (38.3%) husbands responded to a face-to-face
      interview. Visual Analogue Scale was used to measure the level of husband-wife
      communication. Husband-wife communication score was lower on family planning
      compared to other matters. There was a significant fair agreement on the scores
      between the husbands and the wives (p > 0.05) on family planning. There was a
      significant association between husband-wife communication on family planning and
      the current practice of family planning (p = 0.002). The 'likelihood' that
      couples who had had good husband-wife communication to practice family planning
      was about 2.8 times higher compared to those couples with poor husband-wife
      communication (95% C.I.: 1.4, 5.3). Further research need to be carried out, as
      the study was limited by certain constraints.

PMID- 14569743
TI  - Allogeneic haemopoietic stem cell transplantation using non-myeloablative
      conditioning--a local experience.
AB  - Allogeneic haemopoietic stem cell transplantation was initially considered as a
      means of delivering supralethal doses of chemotherapy with or without total body
      irradiation for the treatment of malignancy. However, it has become clear that
      this mode of therapy does not eradicate the malignancy in many patients and its
      benefit is largely due to the immune mediated graft versus malignancy effect.
      This has led to development of alternative strategy to utilize a less intensive
      preparative regimen pre-transplantation that provides sufficient
      immunosuppression to achieve engraftment of an allogeneic stem cell graft, thus
      allowing the evolution of a graft versus malignancy effect post-transplantation.
      Since September 1999, we had carried out 10 cases of allogeneic peripheral blood
      stem cell transplantation: one case of aplastic anaemia, four cases of acute
      myeloid leukemia (AML) in first remission, and five cases of chronic myeloid
      leukemia (CML) in chronic phase. The preparative regimen was non-myeloablative
      comprising Fludarabine with Cyclophosphamide or Busulphan. Recovery from
      transplantation was rapid with no or brief period of neutropenia or
      thrombocytopenia. Engraftment was established by determining donor's short tandem
      repeats in the recipient's bone marrow at day 30, 60 and 100 post
      transplantation. Seven cases (70%) show partial or complete donor's chimerism by
      day 30 indicating successful engraftment. No treatment mortality was noted at day
      100. Graft versus host disease was generally limited. Up to the date of
      reporting, two patients with CML had graft failure, one was successfully re
      transplanted later. Two patients with AML had since relapsed and passed away. The
      others remain alive and well. The cost of transplantation on average was
      estimated to be about a quarter of that using a myeloablative regimen. It appears
      that this treatment strategy is a promising approach for the management of blood
      disorders.

PMID- 14569741
TI  - Audit on tracheostomies performed at the General Intensive Care Unit, Kuala
      Lumpur Hospital.
AB  - During a 6-month period from October 2000 to March 2001, we analysed the
      indications, methods, waiting period and complications following a tracheostomy
      at the General Intensive Care Unit (GIGU) of Hospital Kuala Lumpur. There were 49
      tracheostomies performed during this period. Thirty of them were performed in the
      GICU using the percutaneous dilatational method while 19 were performed
      electively in the Operating Theatre (OT) by the ear, nose and throat (ENT)
      surgeons. The main indications for a tracheostomy were prolonged mechanical
      ventilation and airway protection for patients with a poor Glasgow Coma Scale.
      The average waiting time for a tracheostomy after a decision was made to perform
      one was 1.34 +/- 0.72 days for a percutaneous tracheostomy and 3.72 +/- 2.52 days
      for a surgical tracheostomy. This difference was statistically significant (p <
      0.001). There was excessive bleeding in 3 patients in the percutaneous
      tracheostomy group and 1 patient in the surgical tracheostomy group. Percutaneous
      tracheostomy is now the main method of tracheostomy at the GICU in Hospital Kuala
      Lumpur. Haemorrhage is the most significant complication of this procedure.
      However the overall complication rate is comparable with that of a surgical
      tracheostomy.

PMID- 14569744
TI  - Mutations of the p53 gene in gliomas from Malay patients.
AB  - This is the first investigation performed to detect the presence of the p53
      mutation in Malay patients with gliomas. The p53 gene was amplified using
      polymerase chain reaction (PCR) from 33 fresh-frozen tumour tissues from patients
      histologically confirmed as glioma. Four hot spot areas that lie between exon 5
      to 8 were screened for mutation by mean of non-isotopic "cold" single strand
      conformation polymorphism (SSCP) analysis and direct sequencing. The frequency of
      p53 gene mutation in gliomas examined was 33% (11 of 33). Five (45.5%) cases had
      mutation in exon 7, four (36.4%) had mutation in exon 8 and two (18.1%) had
      mutation in exon 6. Seven (63.6%) of 11 mutations were single nucleotide point
      mutations of which 5 were missense mutations, 1 was nonsense mutation and 1 was,
      silent mutation. Three (27.3%) showed insertion mutation and 1 (9.1%) showed
      deletion mutation. Of the point mutations, 57.1% were transitions and 42.9% were
      transversions. These results suggested that p53 mutations frequently occur in
      gliomas and this gene does play an important role in the tumourigenesis process
      of Malay patients with brain tumours.

PMID- 14569745
TI  - The prevalence of MTHFR 677C-->T missense mutation, total plasma homocysteine
      levels and associated risk factors in Malay subjects.
AB  - The missense mutation of the methylenetetrahydrofolate reductase (MTHFR) gene
      677C-->T is associated with modest elevation of homocysteine levels. The bio
      ecogenetics factors of total homocysteine levels (tHcy) were investigated in a
      cross sectional study involving 53 randomly selected healthy Malay subjects.
      Results indicated that the prevalence of the homozygous 677T/T was 3.8% and
      heterozygous 677C/T was 17.0%. The levels of tHcy was higher in subjects aged
      more than 50 years (n = 7, 11.53 +/- 4.45 mumol/l) and in males (10.99 +/- 3.77
      mumol/l) especially smoking males (12.19 +/- 3.62 mumol/l). THcy levels were low
      in the 3 pregnant subjects (4.44 mumol/l, p = 0.036) who were under folate
      supplementation.

PMID- 14569746
TI  - Staphylococcus aureus carriage in selected communities and their antibiotic
      susceptibility patterns.
AB  - The carriage and antibiotic susceptibility patterns of Staphylococcus aureus in
      the community were determined. Nasal, throat and axillary swabs were taken from
      100 healthy adults and 90 disabled nursing home inmates. Antibiotic disc
      susceptibility testing was conducted following the NCCLS method. Staphylococcus
      aureus carriage was noted in 29% of healthy adults and 47.7% of nursing home
      inmates. Out of 79 strains, resistance to antibiotics were as follows; penicillin
      (92.4%), genetamicin (2.5%), tetracycline (6.3%), fusidic acid (11.3%),
      erythromycin (3.8%), pefloxacin (5.1%), mupirocin (3.8%), amikacin (3.8%),
      ciprofloxacin (2.5%) and chloramphenicol (2.5%). Methicillin-resistant
      Staphylococcus aureus was not isolated. Multiple colonizations and multi
      antibiotic resistant Staphylococcus aureus were shown to occur in healthy
      individuals without risk factors and not previously hospitalized.

PMID- 14569747
TI  - Species distribution and antibiotic resistance of shigella isolates in an urban
      community in Malaysia.
AB  - There is an increasing trend for Shigella isolates worldwide to be resistant to
      commonly prescribed antibiotics. The species distribution and antibiotic
      resistance of Shigella species isolated from children in Kuala Lumpur, Malaysia
      from 1978 to 1997 was reviewed. Three hundred and eighty six isolates were
      positive for Shigella species, representing 1.4% (95% CI: 1.3%-1.6%) of the 26320
      total stool specimens and 13% (95% CI: 11.8%-14.2%) of 2986 isolates positive for
      bacterial pathogens. Shigella flexneri, constituting 74% of all isolates in the
      first five years of the study, decreased by 40% during the last five years (95%
      CI of decrease: 22.1%-57.9%), p-value < 0.0001) to 34%. There was a significant
      reduction (chi2 for linear trend = 77.6, p-value < 0.001) in the number of
      Shigella isolates as a percentage of total stool isolates obtained. 58% of the
      241 isolates tested for antibiotic sensitivity were resistant to at least one
      antibiotic, and 42% wEre multi-resistant to three or more antibiotics. Shigella
      species was not a common pathogen among children admitted with diarrhoea in Kuala
      Lumpur, and was more likely to be resistant to commonly prescribed antibiotics.

PMID- 14569748
TI  - HIV-associated risk behaviour among drug users at drug rehabilitation centres.
AB  - A cross-sectional study to determine the prevalence of Human Immunodeficiency
      Virus (HIV) and HIV-associated risk behavior was conducted in February 1998 among
      6,324 drug users in 26 drug rehabilitation centres in Malaysia. The majority of
      respondents were males (97.3%) and Malays (77.8%), administered drugs
      intravenously (64.6%) and of these 65.4% shared needles. About 78.1% had sexual
      exposure, of which 55.1% had sex with girl friends, 31.3% with prostitutes and
      4.6% with male partners. The HIV prevalence rate in the group was 12.1% and
      significantly high among injecting drug users (IDU); those sharing needles; those
      who started addiction at a young age (10-15 years); those who had sexual
      exposures and had sex with prostitutes.

PMID- 14569749
TI  - An audit of parotidectomy in Singapore: a review of 31 cases.
AB  - A series of 31 consecutive parotidectomies was evaluated. FNAC could
      differentiate tumour from non tumour in 72.8% of cases. For actual histology,
      FNAC was correct in 66.6%. Frozen section was correct in differentiating between
      benign, malignant and inflammatory conditions in all cases. Eighty-eight percent
      of frozen section histology concurred with final histology. The immediate
      postoperative period had 13 cases of facial nerve dysfunction, but only 3 cases
      had residual weakness. The branch most commonly affected was the mandibular
      branch (92.3%). Two patients had Frey's syndrome and one had a traumatic neuroma.
      FNAC and CT scans improve preoperative planning, providing histological evidence
      and the extent of the lesion.

PMID- 14569750
TI  - Addisonian-like crisis in congenital hypopituitarism and cholestatic jaundice.
AB  - A six-week-old male infant was admitted for investigation of cholestasis and pale
      stools. He became lethargic and apnoeic with prolonged seizures after a
      percutaneous liver biopsy. Subsequent investigations showed conjugated
      hyperbilirubinaemia, elevated liver enzymes, and hypoglycaemia. The radinuclide
      hepatobiliary scintigraphy was non-excretory. After an operative cholangiogram,
      the infant developed Addisonian-like crisis with bradycardia, hypotension,
      respiratory distress, metabolic acidosis, hypoglycaemia, hyponatraemia, and
      hyperkalaemia. Blood investigations confirmed congenital hypopituitarism. Hormone
      replacement therapy with L-thyroxine and cortisone acetate resulted in
      dissolution of jaundice and the reduction of the liver size.

PMID- 14569752
TI  - Pancreatitis leading to retroperitoneal fibrosis and ureteric obstruction.
AB  - Two patients who had acute pancreatitis subsequently developed characteristic
      appearance on urography of smooth extrinsic narrowing and medial deviation of the
      right ureter suggestive of retroperitoneal fibrosis (RPF) resulting in ureteric
      obstruction. Both these patients had clinical, biochemical and sonographic
      evidence of acute pancreatitis. CT scan of the abdomen performed on the second
      patient also documented acute pancreatitis. Intravenous urograms were consistent
      with ureteric obstruction due to retroperitoneal fibrosis. Both cases were
      treated conservatively. They were well after an average of 20 months. These 2
      cases illustrate the uncommon association between pancreatitis and RPF.

PMID- 14569751
TI  - Rhinosporidiosis presenting as recurrent nasal polyps.
AB  - Rhinosporidiosis is a chronic granulomatous disease of the mucous membrane,
      predominantly of the nose and nasopharynx. It is uncommon in Malaysia but has
      been seen in immigrant workers from endemic areas like India and Sri Lanka. A
      case seen in Johor is reported here to highlight the need of awareness among
      clinicians at a time where there is increasing numbers of immigrant workers in
      our country. The causative organism of this disease is Rhinosporidium seeberi,
      which is found in stagnant waters. Sporangia and endospores of R. seeberi are
      seen in the granulomatous polypoidal lesions. The patients commonly present with
      epistaxis and nasal blockage. Complete excision is the treatment of choice for
      this disease. Recurrences are common despite anti-microbial treatment.

PMID- 14569754
TI  - Caesarean section rates in government hospitals in Malaysia, 2000-2001.

PMID- 14569753
TI  - Aerodigestive amyloidosis presenting as acute asthma.
AB  - Aerodigestive amyloidosis is a rare disorder characterized by fibrillar protein
      deposition in the aerodigestive tree. We present a case of a 19-year-old Chinese
      gentleman whose diagnosis was initially missed as he presented with features
      suggestive of severe bronchial asthma and was intubated and ventilated. He
      subsequently presented 2 years later with severe stridor and required emergency
      tracheostomy. Current literature is reviewed for the histopathology, common
      clinical features, radiological findings and treatment options for aerodigestive
      amyloidosis.

PMID- 14569756
TI  - Orthopaedic training in Malaysia 1981-2001: two decades of the masters programme.

PMID- 14569757
TI  - Orthopaedic research in Malaysia: our legacy and some thoughts on future
      directions.

PMID- 14569755
TI  - Intestinal parasitic infections in man: a review.
AB  - Intestinal parasites of importance to man are Enterobius vermicularis, the soil
      transmitted helminthes (STH)--Ascaris lumbricoides Tricburis trichiura, bookworms
      (Necator americans/Ancylostoma duodenale) and Strongyloides stercoralis and the
      protozoa Entamoeba histolytica and Giardia duodenalis. Other protozoa such as
      Cryptosporidium sp. and Isopora sp. are becoming important in causing prolonged
      diarrhea in immunocompromised patients. It is estimated that almost 1 billion,
      500 million and 900 million people worldwide are infected by the major nematode
      species--A. lumbricoides, T. trichiura and hookworms respectively. Most of the
      infections are endemic and widely distributed throughout poor and socio
      economically deprived communities in the tropics and subtropics. Environmental,
      socio-economic, demographic and health-related behavior is known to influence the
      transmission and distribution of these infections. In giardiasis, one study
      indicates that age < or = 12 years and the presence of family members infected
      with Giardia were risk factors for infection. Most of the infections occur in
      children and both genders are equally affected. Epidemiological studies of STH
      infections have shown that the prevalence and intensity of infection are highest
      among children 4-15 years of age. The frequency of distribution of STH infections
      is over-dispersed and highly aggregated. areas reinfection can occur as early as
      2 months post-treatment, and by 4 months, almost half of the population treated
      become reinfected. By 6 months the intensity of infection was similar to
      pretreatment level.

PMID- 14569758
TI  - Risk factors for infection in total knee replacement surgery at hospital Kuala
      Lumpur.
AB  - One hundred primary TKR surgeries done between January 1994 and December 1999
      were reviewed after a mean follow-up of 37.4 months. The rate of superficial and
      deep wound infection were 2% and 9% respectively. The most common organism in
      wound infection was Staphylococcus aureus. The factors that were significantly
      associated with superficial wound infection were diabetes mellitus (p = 0.005)
      and Rheumatoid arthritis (p = 0.0000). The factors that were significantly
      associated with deep wound infection were diabetes mellitus (p = 0.000). There
      was no significant difference between duration of surgery, and the mean age among
      patients with and without wound infections.

PMID- 14569759
TI  - Vulnerability of the lower limb in non-fatal motorcycle injuries.
AB  - Motorcyclists form the highest group of fatalities on Malaysian roads. This is a
      prospective study conducted at 3 major hospitals for a period of 12 months to
      determine the type of motorcyclist injuries that usually required
      hospitalization. Four hundred and twelve consecutively injured motorcyclists were
      available for study. One hundred and eighty six (45.15%) were fatally injured and
      226 (54.85%) were seriously injured and surviving. The main cause of fatalities
      was head injury, while lower limb injuries accounted for majority of
      hospitalizations. This study highlights the vulnerability of the motorcyclist to
      lower limb injuries.

PMID- 14569760
TI  - Mechanical failure of Dynamic Hip Screw (DHS) fixation in intertrochanteric
      fracture of the femur.
AB  - We studied 60 intertrochanteric fractures of the femur fixed with Dynamic Hip
      Screw (DHS). There were 10 cases (16.7%) with cutting-out of device through
      femoral head and neck. Stable fracture pattern, postero-inferior and central
      position of screw in the femoral neck and head produced high percentage of good
      result, whereas anterior or superior position of screw produced higher incidence
      of cut-out. We found osteoporosis and distance of screw tip to subchondral bone
      to have no influence on the final outcome.

PMID- 14569761
TI  - Outcome of meniscus surgery at University Malaya Medical Centre.
AB  - Between January 1994 to December 1998, 133 patients had a meniscal surgery at
      University Malaya Medical Centre. Fifty-four patients were assessed and scored
      with the Lysholm and Tegner scoring system. Twenty-nine patients had partial
      meniscectomies and 25 had meniscus repair. The outcome was successful in 80% with
      meniscal repair and 51.7% with partial meniscectomy. The outcome of meniscal
      repair in this study is comparable to other reported series. However, the failure
      rate for partial meniscectomy was high.

PMID- 14569762
TI  - Comparison study between reamed and unreamed nailing of closed femoral fractures.
AB  - Intramedullary nailing is an accepted procedures for femoral fractures gives
      uniformly good results. Various methods of intramedullary fixation have been
      practiced in the past. Recently intramedullary fixation without reaming has come
      into vogue. Preservation of the endosteal blood supply, less blood loss and
      quicker union have been the alleged benefits of not reaming the medullary canal.
      This study is a prospective randomised study conducted to compare intramedullary
      nail fixation of closed femoral fractures with and without a reaming procedure to
      assess the validity of the above assumptions. One hundred and two consecutive
      cases of skeletally mature patients with closed fracture of femoral shaft were
      randomised into two groups, i.e. Reamed (52) and Unreamed (50). The average
      follow-up was 36 weeks (range 28-86 weeks). Average time taken for various stages
      of the operation and total operating time were longer in the reamed group (109.9
      min vs 78.6 min) and the blood loss was also increased (320 mls vs. 190 mls).
      Bridging and callus formation were seen to occur earlier in the reamed group
      compared to the unreamed enabling the patients in the reamed group to return to
      normal functions earlier. Limb length discrepancy and rotational alignment
      measured clinically and with CT scan did not however show any significant
      difference between the two methods. Nails used in this study group were notably
      of a smaller diameter and of shorter length when compared to those used in the
      western population highlighting the difference in the femur in the Asian
      population. Complications were notably more in the unreamed group where these
      were screw breakage (3/50) delayed unions (9/50) and non-unions (4/50). In the
      reamed group however there were only delayed union (2/50) and all fractures
      eventually united without any implant failure. We conclude that closed, reamed,
      antegrade insertion of an intramedullary nail is the treatment of choice in
      femoral shaft fractures, especially those involving the distal 1/3. The unreamed
      procedure should be reserved for certain exceptions, such as in polytrauma, where
      a shorter operative time and less blood loss is desired.

PMID- 14569763
TI  - Are diabetic foot lesions precipitated by accidental trauma?
AB  - Diabetic foot lesions may arise from frictional trauma due to tight or
      inappropriate footwear, repetitive stresses on parts of the foot, overlying bony
      prominence generated by walking and accidental trauma to the neuropathic foot.
      Many diabetics have been found to be unaware of their foot lesion, or know what
      the precipitating cause was. Based on the assumption that accidental trauma would
      affect the foot in a random fashion and result in lesions distributed evenly
      throughout the foot, a study was performed to determine whether foot lesions were
      distributed evenly or concentrated to certain areas of predilection. It was found
      that foot lesions were not evenly distributed but concentrated to certain areas
      of predilection. Even though relatively high proportion of the study population
      walked about in open slippers and barefeet, the study showed that accidental
      trauma was not a predominant precipitant of diabetic foot lesions. Diabetic foot
      lesions tend to occur as a result of cumulative, repetitive trauma to areas of
      prediliection rather than accidental trauma.

PMID- 14569764
TI  - Early remodeling in children's forearm fractures.
AB  - The forearm fracture is a fracture of the upper limb between the elbow and the
      wrist. It is a common injury in children, accounting for more than half of all
      children's fractures, and mostly occur when a child falls on the outstretched
      arm. A difficult clinical problem that often arises is how much angulation can be
      accepted in the child and how much remodeling will occur. One hundred consecutive
      cases of forearm fractures that were admitted at Childrens Orthopaedic Ward,
      Institute of Paediatrics at Hospital Kuala Lumpur between 1st January 1997 to
      31st December 1998 were studied. We found that all fractures united 3 to 6 weeks,
      with a remodeling rate of about 2.5 degrees/month: the proximal fractures having
      the most potential to remodel. We conclude that the early remodeling potential of
      forearm fractures in children is 1.5 degrees/month in midshaft fractures and 2.5
      degrees/month in distal and proximal fractures. We recommend accepting a 10-20
      degree angulation in midshaft fractures, and a 20-30 degree angulation in
      metaphyseal fractures; based on our study of early remodeling potential.

PMID- 14569765
TI  - Crossed-pin versus lateral-pin fixation in pediatric supracondylar fractures.
AB  - A retrospective study was done on 56 patients treated with percutaneous pinning
      of displaced supracondylar fractures of the humerus in the Paediatrics Institute
      of Hospital Kuala Lumpur between November 1999 and October 2000, to ascertain
      whether there is any significance clinically in the stability of a crossed
      pinning medial compared with lateral pinning method. There was equal number of
      patients in each group (28 patients). The radiographs were evaluated for change
      in Baumann's angle and Lateral Humero-capitellar angle from immediate post-op
      until the last follow-up. The changes in the angles did not reveal any
      statistically significant difference in the ability to maintain reduction of the
      fractures. There were 3 instances of iatrogenic ulnar nerve injury in the crossed
      pinning group; the lateral pinning group had 1 case each of anterior interosseous
      nerve and radial nerve injury post operatively. No vascular injury was noted. Two
      cases of superficial pin tract infection were present in each group. The lateral
      percutaneous pinning technique of displaced supracondylar fractures of the
      humerus therefore offers a viable alternative to the crossed pinning group as it
      offers the same stability without the incipient risk of iatrogenic ulnar nerve
      injury.

PMID- 14569766
TI  - Screw osteosynthesis in the treatment of fracture lateral humeral condyle in
      children.
AB  - We reviewed the results of screw osteosynthesis for the treatment of fracture
      lateral condylar physis in twenty children whose average age was six years old
      (range, two to ten years) at the time of operation from January 1998 till
      December 2000. The average interval between the injury and the operation was
      three and half days (range, one day to two weeks). The average duration of follow
      up was one year (range, one year to two years). Osteosynthesis was revised in two
      patients due to anterior placement of screw and rotated distal fracture fragment.
      Osseous union was achieved in all twenty patients. The result was rated excellent
      in nineteen patients and good in one patient.

PMID- 14569767
TI  - Relevance of Cobb method in progressing sagittal plane spinal deformity.
AB  - Non-traumatic, progressing sagittal plane deformities are uncommon, but can lead
      to neurological deficit if untreated. The currently used Cobb method in assessing
      sagittal spinal curves is based on measuring the tilt of the end vertebrae. This
      study describes a method which quantifies the apex of the sagittal curve based on
      the apical quality as measured by the radius of curvature. Both this and the Cobb
      methods are compared to determine which has relevance in determining neurological
      deficit. Radiographs of 36 consecutive patients diagnosed with congenital
      kyphosis were reviewed. Twenty-four had normal neurology and 12 had neurological
      deficit as a result of sagittal curve progression. Both groups of patients had
      their weight bearing lateral radiographs analysed to measure the sagittal curve
      by the usual Cobb method and the Radius of Curvature method. There was no
      difference for the Cobb values for negative neurology and patients with positive
      neurological deficit (p = 0.3). There was a difference in these two groups when
      the radius of curvature method was used (p < 0.0005). The Radius of Curvature
      method has more relevance than Cobb method in quantifying sagittal plane
      deformity in congenital kyphosis when assessing neurological deficit.

PMID- 14569768
TI  - Acute haematogenous osteomyelitis: an unusual complication following a closed
      fracture of the femur in a child.
AB  - We report a rare case of an acute haematogenous osteomyelitis of the femur in a
      five-year-old boy following a closed fracture of the femur. Because of its rare
      occurrence, the diagnosis of osteomyelitis was missed initially. He presented
      with a groin abscess seven weeks after injury. He was treated with external
      fixation, repeated debridements and intravenous antibiotics. Culture grew
      Staphylococcus aureus. The latest follow-up one-year after the injury showed
      resolution of the infection and union of the fracture. The range of knee movement
      is limited from 0-90 degrees due to quadriceps contracture.

PMID- 14569769
TI  - Haemorrhagic lumbar synovial cyst.
AB  - Hemorrhagic lumbar synovial cysts are not commonly reported in English
      literature. Post-resection recurrence of synovial cyst is unusual and therefore
      recurrence symptoms required repeat MRI or CT scan. We reported a case of
      hemorrhagic lumbar synovial cyst presented with neurological deficit that
      recovered initially after surgery but subsequently developed recurrent of
      symptoms at a higher level due to fibrous tissue.

PMID- 14569770
TI  - [Effects of carotid endarterectomy on quality of life of patients with ischemic
      disease of the brain].
AB  - Effects of operation of carotid endarterectomy (CE) on indicators of quality of
      life were investigated in patients with ischemic disease of the brain (IDB). The
      quality of life was assessed in 45 patients at the preoperative stage and in the
      remote postoperative period with the help of questionnaire SF-36. All the
      patients were divided into two groups according to the degree of the initial
      neurological symptoms. The first group included 25 patients with an
      "asymptomatic" or "minimally symptomatic" course of IDB. The second group had 20
      patients with a stable neurological defect resulting from "great" ischemic
      stroke. It was shown that in the first group of patients there was a reliable
      improvement of the life quality after CE in 6 out of 8 indicators. In the second
      group a reliable improvement of the life quality was noted in one of the 8
      indicators only. The average values of the life quality indicators after CE in
      the first group patients were close to those in healthy population. At the same
      time in the second group they were considerably lower. The carotid endarterectomy
      gives the maximum effect of improving the patients' life quality if fulfilled at
      the early stages of IDB and is considered to be of probhylactic character.

PMID- 14569771
TI  - [Morphofunctional features of the gastric stump after different kinds of
      resection for ulcer disease].
AB  - Morphofunctional alterations in the stomach and its stump after resection of 2/3
      of the stomach in modifications of Billroth-1, Hofmeister-Finsterer and Roux
      operations were analyzed in 127 patients with ulcer disease. Chronic experiments
      were carried out in 5 mongrel dogs. A comparative analysis has revealed
      functional and organic advantages of gastroenteroanastomoses after Roux and
      Billroth-I. The Roux resection is an effective operative intervention in patients
      with ulcer disease of the stomach, for chronic duodenal obstruction, and in
      patients with post- gastroresectional pathology. It has an anti-dumping effect,
      provides portional emptying of the gastric stump, improves the life quality of
      the patients.

PMID- 14569772
TI  - [Use of millimeter wave therapy in treatment of acute pancreatitis].
AB  - The observations were performed in 226 patients with acute destructive
      pancreatitis. In 152 patients the medical complex was supplemented with a program
      of photo-millimeter-wave therapy in which the electromagnetic radiation of the
      millimeter diapason combined with red and green light was used with due regard
      for the disease stage. The inclusion of photo-millimeter-wave therapy in the
      complex of treatment starting from the 2-3 days of disease promoted a decrease of
      the systemic inflammatory reaction, rapidly improved the general condition of the
      patients, reduced the occurrence of infectious forms of pancreanecrosis,
      lethality and time of hospital staying of the patients. The inclusion of photo
      millimeter-wave therapy since the 10-15th day did not influence the duration of
      hospitalization but resulted in more favorable course of the disease and less
      lethality.

PMID- 14569773
TI  - [Early diagnosis of orthostasis disturbances].
AB  - The observations were carried out in 51 healthy volunteers (26 men and 25 women)
      who underwent passive orthotest with the registration of thoracic impedance (TI).
      It was found that women had a higher index of TI both in rest and in dynamics of
      the performance of the orthostatic test than men. In 10 subjects the increase of
      TI in orthostasis was higher than 15% that can be supposed to be a criterion of
      the pathological drop of the venous return. The TI dynamics in performing the
      orthotest was quicker than changes in AP and the appearance of complains can be
      taken for a preclinical symptom of latent volume disturbances in the orthostatic
      regulation that has an important diagnostic value.

PMID- 14569774
TI  - [Types of coaptation of nerve fiber bundles and effectiveness of the nerve
      suture].
AB  - Experiments in 26 dogs were carried out in order to analyze the quality of
      comparing the nerve fiber bundles, morphometrical and functional parameters of
      regeneration after the restoration of the nerve with a standard epineural
      microsurgical suture and by an original method including the coaptation of the
      freshened ends by a relaxation transneural suture followed by epiperineural
      microneurorrhaphy. Five variants of the comparison of the nerve fiber bundles in
      the suture zone are described. The results of expert assessments and computed
      morphometry allowed to register higher indices of regeneration and
      differentiation of nerve fibers.

PMID- 14569775
TI  - [The biochemical markers of bone metabolism in differential diagnosis of
      hematogenic osteomyelitis of foot bones and acute stage of diabetic
      osteoarthropathy].
AB  - The determination of the level of leukocytes and ESR in 25 patients was shown to
      be of low informative value in differential diagnostics of destructive injuries
      of feet in patients with diabetes mellitus. An analysis of the biochemical
      markers of the bone remodeling has demonstrated high informative value of this
      method in differential diagnostics of acute stage of diabetic osteoarthropathy
      and osteomyelitis that allows to use it in complex examinations of osteomyelitis
      suspects.

PMID- 14569776
TI  - [The use of pre-differentiated mesenchymal bone marrow stem cells for treatment
      of deep burn wounds].
AB  - The opportunity of faster closing deep burn wounds by using fibroblast-like
      mesenchymal bone marrow stem cells (FMSC) and embryonic fibroblasts (EF) was
      investigated in rats. It was shown that FMSC as well as EF transplanted onto burn
      surfaces reduced the expression of cell infiltration but accelerated the
      formation of vessels de novo and granulation tissue in the wounds. These changes
      form the conditions for faster closing the burn wounds as compared to the control
      wounds (without cell transplantation). High rate of wound closing induced by FMSC
      and EF is thought to be caused by a long period (up to 30 days) of vital activity
      of the cells grafted on the burn surface. It was also found out that the rate of
      wound regeneration induced by FMSC was higher that that induced by EF.

PMID- 14569777
TI  - [Problems of prehospital care for a severe combined trauma].
AB  - The authors have analyzed the strategy and results of treatment of 455 casualties
      at the prehospital stage. Main defects of giving help at the prehospital stage
      and ways to improve it are described.

PMID- 14569778
TI  - [Morphofunctional characteristic of enteral insufficiency and means of
      nutritional maintenance in casualties with a severe trauma].
AB  - Examinations of 257 casualties were performed at different terms after trauma.
      The criteria for determination of the degree of enteral insufficiency in patients
      with traumas were the severity of the injury, the severity of the state, the
      absorption state in the small intestine and the degree of errosive-ulcerous
      processes in the upper parts of the gastro-intestinal tract. The clinico
      laboratory gradation of the enteral insufficiency was developed according to the
      severity degree that allows to establish the algorithm of its diagnosing and
      treatment based on the principle of outstripping therapy of the appearing
      disorders and to optimize the terms and methods of the nutritional maintenance of
      the patients with traumas.

PMID- 14569779
TI  - [Proinflammatory cytokines in wound discharge and peripheral blood in patients
      with gunshot osteomyelitis of extremities].
AB  - Examination of 36 patients with gunshot osteomyelitis of extremities having the
      disease during 1-5 years has established that in acute gunshot osteomyelitis the
      concentration of antiinflammatory cytokines was rapidly increasing both in the
      blood serum and in the wound discharge. In the chronic course of the process the
      concentration of antiinflammatory cytokines in blood is a little higher than
      normal and only an analysis of the wound discharge can reflect the dynamics of
      the inflammatory (suppuration) process.

PMID- 14569780
TI  - [Experimental evaluation of the wound healing dynamics].
AB  - The experimental clinical investigation of the influence of systemic
      enzymotherapy on the course of the wound process was carried out in rats and in
      clinic. The rats of the experimental group have demonstrated more rapid
      debridement of the wound from blood clots and tissue detritus, intensive
      formation of granular tissue and its ripening. The experimental investigation has
      shown that using the preparation of systemic enzymotherapy (Vobenzyme) stimulates
      processes of healing at the expense of quicker changing the inflammation phases
      as well as prevents the development of early and late complications on the side
      of postoperative wounds. It was confirmed by clinical observations in 36 patients
      from 4 to 14 years of age.

PMID- 14569781
TI  - [Surgical complications of the combined treatment of rectum carcinoma with
      preoperative irradiation].
AB  - An analysis of results of treatment of 323 patients has shown that the
      postoperative complications and continence of feces and gases (incontinence) is
      not more frequent than after preoperative irradiation in total dose up to 25 Gy.

PMID- 14569782
TI  - [Effects of intraoperative reservation and reinfusion of autologous blood on the
      function of lungs in patients with ischemic heart disease].
AB  - A retrospective examination of 127 patients has been performed who underwent
      operations of coronary bypass under conditions of hypothermic extracorporeal
      circulation. It was shown that both the reservation of autoblood (volume about
      10% of circulating blood) and the following reinfusion failed to result in a
      substantial change of the lung functions. The reservation-reinfusion of autoblood
      in IHD patients operated on by direct revascularization of the myocardium under
      conditions of extracorporeal circulation did not influence the indices of
      ventilation (the volume of functional dead space), pulmonary blood flow (fraction
      of venoarterial intrapulmonary shunt, mean pressure in the pulmonary artery),
      diffuse capacity of the lungs (the arterial/alveolar ratio).

PMID- 14569783
TI  - [Prophylaxis of endotoxicosis in the early postoperative period in patients with
      malignant tumors of the colon].
AB  - A combination of intraoperative pharmacological Pentamine blockade by the method
      of increased resistance to its hypotensive effect and postoperative epidural
      block in the scheme of multicomponent combined general anesthesia allows to
      provide adequate protection of organism against surgical aggression and prevent
      the development of endotoxicosis at the early postoperative period in patients
      with malignant tumors of the colon with a coexisting pathology of the cardio
      vascular system.

PMID- 14569784
TI  - [Evaluation and prognosis of patients' health status in postop period].
AB  - An estimation of the patient's state and the prognosis can be made at the
      postoperative period on the basis of results of the assessment of complement
      activity, blood cell hemolysate activity, filtration of serum and urine. Of the
      greatest clinical significance for the estimation of the patient's state is
      complement activity and toxicity of urine.

PMID- 14569785
TI  - [Surgical strategy for perforating typhoid ulcers].
AB  - The authors share their experiences with operative treatment for perforation of
      typhoid ulcers in 15 patients. The dissection of ulcerous infiltrate followed by
      simple suturing was fulfilled in 4 out of these patients against the background
      of diffuse purulent peritonitis. All the patients died. So, in order to reduce
      lethality in the following patients we either fulfilled resection of the gut
      within the limits of not involved tissues with ileostomy if the patient had
      diffuse purulent peritonitis or made primary interintestinal anastomosis in cases
      without it. In both cases a microirrigator was introduced in the small intestine
      mesentery for administration of antibiotics at the postoperative period. It
      allowed to make lethality lower.

PMID- 14569786
TI  - [Comparative assessment of different methods of treatment of chronic critical
      ischemia of lower extremities in elderly and senile patients].
AB  - Results of using different methods of treatment of chronic critical ischemia of
      lower extremities were analyzed in 267 elderly and senile patients. Ischemia of
      the lower extremities of the III degree was noted in 83% of the patients, the IV
      degree ischemia--in 17%. In 86 patients who underwent primary high amputation of
      the lower extremity 2 years survival was noted in 33.7%. In 89 patients treated
      conservatively during 12-14 days good and satisfactory results were obtained in
      58.4%, amputations were made in 41.6%. The 2 years survival was 66.3%. In 92
      patients primary reconstructive operations resulted in good and satisfactory
      outcomes in 75 (81.5%) out of them with the 2 years survival in 88.0%.

PMID- 14569787
TI  - [Optimization of surgical treatment of acute superficial varicose
      thrombophlebitis].
AB  - Complex examination and the following treatment of 142 patients with acute
      superficial varicothrombophlebitis were analyzed. The patients were divided into
      2 groups. The first group consisted of 41 patients who were subjected to
      venectomy in the acute period of the disease, the second group--of 101 patients
      with two stages of treatment. At the first stage sclerosurgical technologies were
      used to arrest the inflammatory process. At the second stage the thrombosed
      varicose veins were surgically ablated. In the first group patients complications
      at the early postoperative period developed in 17% of cases, at the late period-
      in 14.6%. In the second group complications were noted in 3 and 2% of cases
      respectively.

PMID- 14569788
TI  - [Internal carotid artery thrombosis in skull base fractures].

PMID- 14569789
TI  - [Successful application of reflux-free jejunostomy in treatment esophagoplasty
      postop complications].

PMID- 14569790
TI  - [Rare etiology of duodenal obstruction].

PMID- 14569791
TI  - [Wound infection as etiology of fulminant sepsis].

PMID- 14569792
TI  - [Comparative study of centralized and decentralized outpatient surgical
      services].
AB  - The results of work of decentralized and centralized out-patient surgical service
      in two regions of the city of Novokuznetsk are compared. The authors make a
      conclusion that the centralized out-patient surgical service has a number of
      advantages as compared with the decentralized service since it allows to
      concentrate the material resources, to improve the staff of specialists, to widen
      the volume and spectrum of the medical care and makes prerequisites for
      profitable work of the institution under conditions of the market relations and
      competition.

PMID- 14569793
TI  - [The role of diagnostic and treatment quality in differential salary of hospital
      surgeons].
AB  - One of the priority trends in the work of medical institutions is the development
      of suggestions on the payment for the work of the medical staff depending on the
      volume and quality of treatment. The assessment of the work of 3 resident doctors
      of the department was performed in 1180 patients with special reference to the
      rating, complexity of the case of hospital management, working load, integral
      coefficient of the quality. The role of the diagnosis and treatment quality for
      differential payment was determined.

PMID- 14569794
TI  - [Vagotomy in patients with chronic duodenal ulcer complicated by bleeding].

PMID- 14569795
TI  - [Prospects of treatment of patients with the diabetic foot syndrome].

PMID- 14569796
TI  - ONA takes lead in forming state nurse disaster response team.

PMID- 14569797
TI  - Environmental implications of HIPAA.

PMID- 14569798
TI  - Property in potential human life?--Predicting a Canadian approach.

PMID- 14569799
TI  - Cartilaginous lesions of the skeleton.
AB  - Cartilaginous lesions of the skeleton include those due to genetic diseases
      (skeletal dysplasias), reparative and hamartomatous processes, and benign and
      malignant tumors. We review the lesions most commonly encountered by the surgical
      pathologist, their differential diagnoses, and recently discovered features of
      these lesions.

PMID- 14569800
TI  - Measuring HER-2 in breast cancer. Immunohistochemistry, FISH, or ELISA?
AB  - Measuring HER-2 is important for selecting optimal therapy and predicting
      prognosis in breast cancer patients. Current methods for evaluating HER-2 include
      measuring protein overexpression by immunohistochemistry (IHC), measuring gene
      copy number by fluorescent in situ hybridization (FISH), and measuring shed
      antigen in the serum by enzyme-linked immunosorbent assay (ELISA). This review
      compares these 3 methods and analyzes the current literature pertaining to this
      subject. In comparing IHC with FISH, the negative predictive value is excellent
      for commonly used commercial antibodies but the positive predictive value is
      highly variable. However, by considering only strongly staining cases as positive
      by IHC, the positive predictive value is markedly improved. ELISA is useful in
      the follow-up care of patients with breast cancer. An algorithm for using all 3
      methods is presented.

PMID- 14569801
TI  - Urothelial neoplasms of the kidney and ureter. An epidemiologic, pathologic, and
      clinical review.
AB  - Urothelial neoplasms occur with varying frequency at different sites along the
      urothelial tract. Approximately 5% of urothelial neoplasms occur in the kidneys
      and ureters, while the majority of these tumors occur in the urinary bladder.
      Consequently, urothelial disease of the bladder has been evaluated to a greater
      extent than urothelial tumors elsewhere, and many of the features of bladder
      urothelial neoplasms have been applied to these tumors at other sites. While the
      classification of urothelial neoplasms is the same for tumors in the bladder,
      kidney, and ureter, there are some features of urothelial neoplasms of the kidney
      and ureter that are unique to these sites. An epidemiologic, pathologic, and
      clinical review of urothelial neoplasms of the kidney and ureter is presented.

PMID- 14569802
TI  - Gastrointestinal stromal tumors. A review of characteristics morphologic,
      immunohistochemical, and molecular genetic features.
AB  - Gastrointestinal stromal tumors are a heterogeneous group of neoplasms composed
      of either spindled or epithelioid cells that have distinctive histologic
      appearances and clinical behaviors in different portions of the gastrointestinal
      tract. These tumors are best evaluated in a site-specific manner, and prediction
      of clinical behavior is best achieved by evaluation of multiple characteristics,
      including cell type, cellularity, nuclear pleomorphism, mitotic counts, and the
      presence or absence of mucosal invasion and tumor cell necrosis. The vast
      majority of these tumors can be reliably placed into benign or malignant
      categories using a constellation of morphologic features. Almost two thirds of
      these tumors arise in the stomach, and slightly less than one third occur in the
      small bowel. The remaining tumors arise (in descending order of frequency) in the
      anorectum, large bowel, and esophagus. These tumors uniformly express CD117, and
      mutations of the c-kit gene are central to their pathogenesis and likely the key
      to effective therapeutic intervention.

PMID- 14569803
TI  - ASCUS in Papanicolaou smears. Problems, controversies, and potential future
      directions.
AB  - Each year, an estimated 2 to 3 million women in the United States receive a
      Papanicolaou smear diagnosis of atypical squamous cells of undetermined
      significance (ASCUS). There is no uniform practice for the diagnosis or
      management of these patients, and the annual cost of aggressively treating ASCUS
      lesions is estimated to be billions of dollars. Since its introduction in 1988,
      ASCUS has been problematic and controversial. ASCUS is a problem to define, to
      diagnose, to reproduce, and to manage. The following article reviews the various
      aspects and problems of ASCUS, its controversies regarding diagnosis,
      reproducibility, and management, and discusses the possible future directions of
      this category in light of the recent Bethesda System 2001 Workshop
      recommendations.

PMID- 14569804
TI  - A practical approach to the diagnosis of Hodgkin lymphoma.
AB  - The diagnosis of Hodgkin lymphoma has become more difficult in recent years,
      paradoxically because of great strides made in the understanding of the molecular
      mechanisms driving the lymphomas. Extensive panels of monoclonal antibodies,
      coupled with flow cytometric analyses and molecular diagnostic studies, have
      served to define more lymphoma subtypes that cannot be identified based on
      morphologic evidence alone. This overview is intended to provide useful criteria
      for the recognition of Hodgkin lymphoma and to recommend tools that will aid in
      separating Hodgkin lymphoma from a series of common benign and malignant look
      alikes. The relationships among Hodgkin lymphoma, the B-cell non-Hodgkin
      lymphomas, and the T-cell non-Hodgkin lymphomas are discussed, and useful
      immunohistochemical markers for the routine diagnosis of Hodgkin lymphoma are
      suggested.

PMID- 14569805
TI  - The evaluation of infertility.
AB  - Infertility is a significant medical problem that affects many couples.
      Evaluation is the starting point for treatment of infertility as it may suggest
      specific causes and appropriate treatment modalities. Although the history and
      physical examination provide important information, specific diagnostic tests are
      required to evaluate infertility. Because the causes of infertility can be
      multifactorial, a systematic approach typically is used and involves testing for
      male factor, ovulatory factor, uterotubal factor, and peritoneal factor. Many of
      these diagnostic tests are laboratory based, including semen analysis, serum
      progesterone level, serum basal follicle-stimulating hormone level, and
      clomiphene citrate challenge, and can be done by the primary care physician.
      Moreover, by understanding the infertility evaluation, the primary care physician
      can serve as an important resource for advice about infertility. This article
      briefly reviews the diagnostic approach to infertility, with particular emphasis
      on important laboratory tests used for evaluation.

PMID- 14569806
TI  - Prostate-specific antigen and the early diagnosis of prostate cancer.
AB  - With digital rectal examination (DRE), prostate-specific antigen (PSA) is a major
      screening tool for prostate cancer. PSA is specific for the prostate, but not for
      prostate cancer. Multiple factors influence PSA value. Determination of PSA
      levels is not 100% sensitive for prostate cancer, as PSA levels may be normal
      despite presence of prostate cancer. The cutoff value for PSA of 4.0 ng/mL gives
      the highest sensitivity and highest specificity. Several modifications of PSA
      testing have been developed and may be beneficial for select populations.
      Uncertainty about the natural progression of prostate cancer and inherent
      limitations of PSA testing make it unclear whether universal screening is
      beneficial, and the recommendations of various organizations conflict. Randomized
      studies are in progress to address the role of PSA testing and of modifications
      of this test in the early detection of prostate cancer.

PMID- 14569807
TI  - Laboratory tests for the diagnosis of cystic fibrosis.
AB  - Cystic fibrosis (CF) remains the most common life-limiting inherited disease in
      America. Making an accurate, early diagnosis is essential to the management of
      the disease. The diagnostic criteria for CF require the presence of 1 or more
      typical clinical features, a family history of CF, or a positive newborn
      screening test, plus laboratory evidence of the CF transmembrane conductance
      regulator (CFTR) dysfunction. In the past, the laboratory test of abnormal CFTR
      function was based largely on an elevated sweat chloride test result. The recent
      development of a genotypic CFTR mutation screen has greatly improved diagnostic
      accuracy. Increased screening of the CFTR locus has led to the recognition of a
      number of atypical CF disorders. Recently, a 2-tiered newborn screening protocol
      including CFTR genotyping has become popular, increasing the likelihood of early
      diagnosis.

PMID- 14569808
TI  - Bioterrorism. Clinical recognition and primary management.
AB  - The recent anthrax attacks in the United States have demonstrated the reality of
      bioterrorist threats as well as the need for preparedness and planning to mount a
      successful response to such events. Medical practitioners have a key role in
      responding to bioterrorist activity because they can contribute to the timely
      recognition of an event and to the mitigation of morbidity resulting from a
      bioterrorist attack. The medical community needs to become familiar with how to
      recognize and manage diseases produced by the biologic agents that might be used
      by terrorists. This review summarizes the microbiological and clinical aspects of
      the agents of anthrax, smallpox, plague, and tularemia, which are all considered
      likely bioterrorist weapons.

PMID- 14569809
TI  - Tuberculosis. Advances in laboratory diagnosis and drug susceptibility testing.
AB  - Laboratory diagnosis of mycobacterial infection is complicated by the fastidious
      growth requirements of the bacillus organism. Delays in diagnosis can impede
      effective treatment and surveillance of the disease. Control of Mycobacterium
      tuberculosis has also been aggravated by the emergence of multidrug-resistant
      tuberculosis, and enhanced methods of antibiotic susceptibility testing are
      needed. Molecular laboratory techniques and advances in rapid culture methods
      have led to the development of diagnostic and drug susceptibility tests that are
      rapid and reliable. This article describes recent innovations in the molecular
      diagnosis and antibiotic susceptibility testing of M tuberculosis.

PMID- 14569810
TI  - Laboratory testing for viral hepatitis.
AB  - Worldwide, infection with hepatitis viruses remains a major clinical and public
      heath concern. The laboratory is an integral part of the diagnosis of these
      infections since many of the manifestations are nonspecific, and the various
      hepatitis viruses show overlapping symptomatology. In this article, we discuss
      the laboratory diagnosis of viral hepatitis with special attention to the
      diagnostic approach for each of the major entities.

PMID- 14569811
TI  - HIV update. Diagnostic tests and markers of disease progression and response to
      therapy.
AB  - HIV-1 infection continues to present diagnostic and management challenges on a
      global scale. Multiple testing strategies currently are used for evaluation of
      patients and infection status. Serologic testing represents the standard for
      diagnosis of HIV-1 infection. Molecular methods enable screening of the blood
      supply, detection of vertical transmission, and viral load testing to monitor
      patients during therapy. Molecular resistance testing facilitates the assessment
      of viral quasi species and the presence of specific mutations that confer
      antiviral resistance. Both genotyping and phenotyping approaches have been
      adopted for HIV-1 drug-resistance testing and enable rational modification of
      therapies for patients in whom their current regimens are failing.

PMID- 14569812
TI  - Cutaneous adnexal neoplasms.
AB  - Cutaneous adnexal tumors are a large and diverse group of tumors that are
      commonly classified according to their state of appendageal differentiation:
      eccrine, apocrine, follicular, and sebaceous. These tumors generally behave in a
      benign manner, but malignant types exist. Most adnexal tumors are not common
      enough to permit most practitioners to maintain a ready familiarity with them,
      but they also are not rare. We provide a brief review of the clinical,
      histopathologic, and other relevant features of some adnexal tumors we believe
      the practitioner has the greatest likelihood of seeing in daily service. We also
      enumerate criteria the practitioner can use to distinguish between tumors likely
      to behave in a benign rather than a malignant manner.

PMID- 14569813
TI  - Benign fibro-osseous diseases of the maxillofacial bones. A review and
      differential diagnosis.
AB  - Benign fibro-osseous lesions (BFOLs) of the maxillofacial bones represent a
      diverse group of pathologic conditions that includes developmental lesions,
      reactive or dysplastic diseases, and neoplasms. Owing to substantial overlap of
      the histopathologic findings, subclassification of BFOLs may be problematic.
      Moreover, this is not merely an academic exercise because the therapeutic
      management of BFOLs varies depending on the actual disease process. To further
      complicate matters, a number of other disease processes demonstrate clinical,
      radiographic, and microscopic features that bear resemblance to those encountered
      in recognized fibro-osseous conditions. The objective of this article is to
      review the most current clinicopathologic, radiographic, and molecular studies of
      BFOLs to aid the surgical pathologist in the recognition and diagnosis of this
      diverse group of maxillofacial lesions. A discussion of the various disease
      processes that occasionally may be confused with BFOLs also is included.

PMID- 14569814
TI  - Blood substitutes. What they are and how they might be used.
AB  - Three classes of materials have been studied as potential blood substitutes:
      modified hemoglobin solutions, perfluorocarbon emulsions, and liposome
      encapsulated hemoglobin. The first two have reached phase III clinical trials,
      while the third remains in the preclinical state of testing. Hemoglobin is a
      highly active molecule; hence, modification has been required to avoid potential
      deleterious effects. Although there has been considerable progress toward
      bringing such a product to the clinical setting, its development has challenged
      our understanding of oxygen delivery and use. The perfluorocarbon emulsions have
      been studied primarily for roles other than as equivalents of conventional banked
      units of RBCs for transfusion. The study of these molecules has added to our
      understanding of basic physiologic processes.

PMID- 14569815
TI  - Expression of anaplastic lymphoma kinase in non-Hodgkin's lymphomas and other
      malignant neoplasms. Biological, diagnostic, and clinical implications.
AB  - Accumulating evidence indicates that expression of anaplastic lymphoma kinase
      (ALK), typically due to t(2;5) translocation that creates an NPM-ALK fusion gene,
      defines a distinct type of T/null-cell lymphoma (TCL) within a vastly
      heterogeneous group of anaplastic large cell lymphomas. Through the translocation
      mechanism or as a full-length apparently intact protein, ALK also is expressed by
      a subset of inflammatory myofibroblastic tumors, glioblastomas, diffuse large B
      cell lymphomas, and other malignant neoplasms. Owing to the recent progress in
      understanding its pathogenesis, ALK+ TCL has become a model malignant neoplasm in
      which morphology-based diagnosis and classification are gradually shifting toward
      biology-based diagnosis. Several lines of experimental evidence indicate that the
      ectopically expressed ALK is oncogenic in ALK+ TCL by being constitutively active
      owing to autophosphorylation and, consequently, by stimulating several critical
      signal transduction pathways involving phospholipase C-gamma, AKT, and STAT3
      (signal transducer and activator of transcription 3). Targeting ALK and, perhaps,
      its downstream signaling effector proteins represents a promising novel
      therapeutic approach to ALK+ TCL. Diagnostic implications of the ALK expression
      in ALK+ TCL and other malignant neoplasms and the related current controversies
      are discussed.

PMID- 14569816
TI  - Cardiac markers for myocardial infarction. A brief review.
AB  - Blood testing for biomarkers of myocardial injury plays an increasingly important
      role for the evaluation, diagnosis, and triage of patients with chest pain. The
      guidelines for the diagnosis of myocardial infarction (MI) have recently changed
      and prominently incorporate the results of cardiac marker testing in the clinical
      definition of MI. We review these updated guidelines for MI definition as it
      pertains to cardiac biomarker testing and further compare the differing biology
      and release kinetics of clinically relevant biomarkers. Finally, we define the
      contemporary use of cardiac biomarker testing for patients with chest pain,
      including appropriate integration of point-of-care testing into day-to-day
      clinical use.

PMID- 14569817
TI  - Review of fine-needle aspiration cytology of salivary gland neoplasms, with
      emphasis on differential diagnosis.
AB  - The widespread use of fine-needle aspiration (FNA) biopsy of salivary gland
      lesions in many centers is testimony to its usefulness and acceptance as a
      diagnostic technique. Many pertinent questions concerning a mass arising in the
      salivary gland can be answered by evaluation of FNA cytologic material, and these
      include whether the mass is truly of salivary gland origin, whether the lesion is
      inflammatory or neoplastic, and if neoplastic, whether benign or malignant. On
      diagnosis of a neoplastic salivary gland lesion, the next important issue is to
      correctly classify the tumor, particularly if malignant. Specific cytologic
      diagnoses can be achieved in the majority of cases, thus enabling the clinician
      and patient to make appropriate informed decisions. The cytologic evaluation of
      salivary gland tumors, however, is limited by the wide range and heterogeneous
      nature of benign and malignant tumors arising in this area, many of which share
      similar or show overlapping cytologic features, making the diagnosis of rare
      tumors problematic. In this review, the cytologic features of the major salivary
      gland neoplasms, the differential diagnoses, and the salient points that, if
      examined carefully, help achieve a specific diagnosis are discussed.

PMID- 14569818
TI  - Molecular mutations in thyroid carcinogenesis.
AB  - Molecular mutations in thyroid carcinomas have been well characterized and
      studied and consist of both germline and somatic genetic events. Mutations that
      are associated with tumorigenesis can be divided into 2 general categories:
      oncogene mutations and tumor suppressor gene mutations. Thyroid tumors and their
      characteristic molecular mutations are discussed in this review. The current
      practice in diagnostic testing for thyroid tumors also is examined.

PMID- 14569819
TI  - Gray matter involvement in multiple sclerosis: a new window into pathogenesis.

PMID- 14569820
TI  - Roles for imaging in understanding the pathophysiology, clinical evaluation, and
      management of patients with mitochondrial disease.
AB  - Primary mitochondrial disorders remain uncommon, but they enter into the
      differential diagnosis for a broad range of syndromes. Functional and structural
      imaging methods offer important clinical tools for patient assessment when these
      diseases are suspected. Although the findings are not specific, in the
      appropriate clinical context, these tests can guide the use of more specific or
      invasive investigations. They have provided considerable information concerning
      the underlying pathophysiology of this heterogeneous range of disorders.
      Monitoring these changes potentially facilitates the identification of new
      therapies and their individualization.

PMID- 14569821
TI  - Brain perfusion imaging of a craniopharyngioma by transcranial duplex sonography.
AB  - BACKGROUND AND PURPOSE: The aim of this study was to test a new ultrasound
      software tool to assess pathological perfusion in a brain tumor patient. METHODS:
      Tissue harmonic imaging (THI) enables an improved depiction of brain morphology,
      employing nonlinear parenchyma and ultrasound contrast agent (UCA) backscatter
      information. With specialized software, morphological information can be
      separated from perfusion information. Both can be superimposed at a preferred
      mixing ratio in a single image. RESULTS: Using THI and a perfluoropropane-based
      UCA, a pathologic perfusion pattern described by abnormal perfused areas in the
      tumor region could be demonstrated. After superimposing morphologic and perfusion
      information, subtle structural tumor inhomogeneities were depicted.
      Craniopharyngioma structure and perfusion defect were confirmed by T2-weighted
      and perfusion-weighted magnetic resonance imaging. CONCLUSION: Transcranial
      duplex sonography in combination with contrast specific imaging methods might be
      helpful to visualize perfusion defects without loss of morphological information.

PMID- 14569822
TI  - Thalamic involvement in multiple sclerosis: a diffusion-weighted magnetic
      resonance imaging study.
AB  - BACKGROUND AND PURPOSE: Injury to deep gray matter structures in multiple
      sclerosis (MS) has been suggested by recent neuro-imaging and neuropathology
      studies. Diffusion-weighted magnetic resonance imaging (MRI) can assess tissue
      damage with greater sensitivity than conventional MRI. The authors' objective was
      to assess thalamic gray matter damage by diffusion-weighted imaging in MS
      patients. METHODS: This was a retrospective study performed at a tertiary care,
      university-affiliated comprehensive MS center of 82 MS patients and 43 controls.
      The main outcome measures were thalamic apparent diffusion coefficients (ADCs),
      whole-brain atrophy (brain parenchymal fraction), fluid-attenuated inversion
      recovery (FLAIR) hypertense lesion volume, and clinical course. RESULTS: ADCs in
      the left thalamus were higher in MS patients (0.741 +/- 0.044 x 10(-3) mm2/s)
      than controls (0.723 +/- 0.036 x 10(-3) mm2/s) (P = .027) and higher in secondary
      progressive MS patients (0.761 +/- 0.044 x 10(-3) mm2/s) than relapsing-remitting
      MS patients (0.735 +/- 0.032 x 10(-3) mm2/s) (P = .029). ADCs in the right
      thalamus were higher in secondary progressive MS patients (0.784 +/- 0.069 x 10(
      3) mm2/s) than controls (0.757 +/- 0.038 x 10(-3) mm2/s) (P = .033). In the MS
      group, left thalamus ADCs correlated negatively with brain parenchymal fraction
      (r = -0.30, P = .008), total left hemispheric FLAIR lesion volume correlated with
      ADCs in the left (r = 0.35, P = .001) and right (r = 0.39, P < .001) thalami, and
      total right hemispheric FLAIR lesion volume correlated with ADCs in the left (r =
      0.31, P = .006) and right thalami (r = 0.22, P = .048). CONCLUSION: MS patients
      have increased water diffusion in the thalamus that is partly associated with
      clinical course, lesion load, and whole-brain atrophy. Both indirect and direct
      mechanisms of gray matter injury may play a role in the pathophysiology of MS.

PMID- 14569823
TI  - Contrast M-mode power Doppler ultrasound in the detection of right-to-left
      shunts: utility of submandibular internal carotid artery recording.
AB  - Cardiac right-to-left shunts (RLSs) can be detected by echocardiography and
      transcranial Doppler ultrasound (TCD). In patients without adequate transtemporal
      bone windows, results may be obtained by insonating extracranial arteries;
      however, the sensitivity and practicality of this approach is unknown. In 34
      patients evaluated with echocardiography for RLSs, 73 studies were performed with
      unilateral, simultaneous contrast TCD (cTCD) of the middle cerebral artery (MCA)
      and anterior cerebral artery (ACA) and submandibular power M-mode Doppler (PMD)
      ultrasound of the extracranial internal carotid artery (ecICA). The number of
      microbubble (MB) signals and their times of first appearance were determined. RLS
      volume was graded on 6 levels (I = trace, II = small, III = medium, IVa = large,
      IVb = shower, IVc = curtain) and compared between MCA and ecICA recordings. In 2
      of 24 cTCD studies in 15 patients without evidence of RLSs on single-gated MCA
      monitoring, low-volume RLSs (grades I and II) were detected via ecICA insonation;
      in both, MB signatures were tracked in the ecICA, passing into the ipsilateral
      ACA. In 40 of 49 studies (26 patients) in which RLSs were demonstrated with
      single-gated MCA monitoring, more MBs were detected in the ecICA than the MCA,
      with either single-gated or M-mode images, with increases of 76.9% and 66.1%,
      respectively (P = .027). Compared to single-gated studies, M-mode technology
      detected nonsignificant increases in MB number in both the MCA and the ecICA (by
      20.2% and 14.0%, respectively). Contrast PMD with cervical ICA recording is at
      least as sensitive and specific as the traditional MCA method in detecting RLSs;
      furthermore, this method seems to be more sensitive for low-volume RLSs (grades I
      III) because of air MB decay (9.2%) and entry into the ipsilateral ACA (34.2%).
      This is in concordance with the increase of detected RLS grades observed in 32.7%
      of patients with echocardiography-documented RLSs. The authors therefore suggest
      the incorporation of ecICA PMD not only in patients with poor ultrasonic bone
      windows but also in every patient being evaluated for suspected RLSs.

PMID- 14569824
TI  - A multiple regression model of combined duplex criteria for detecting threshold
      carotid stenosis and predicting the exact degree of carotid stenosis.
AB  - BACKGROUND AND PURPOSE: Combined duplex criteria are commonly used in vascular
      laboratories for evaluating carotid stenosis. However, most of these combinations
      are empirical, and systemic validation is lacking. This study was completed using
      a multiple regression method to evaluate the accuracy of different combined
      duplex criteria for detecting threshold carotid stenosis and predicting the exact
      degree of carotid stenosis on angiography. METHODS: Two hundred sixty-six sets of
      unilateral carotid duplex and angiographic data were randomly divided into 2
      sets: a derivation set and a validation set. The derivation set was used to
      develop a multiple logistic regression model for detecting 70% threshold carotid
      stenosis. Age, sex, systolic blood pressure, diastolic blood pressure, Doppler
      peak systolic velocity (PSV), Doppler and diastolic velocity (EDV), the systolic
      carotid ratio (SCR), and ophthalmic artery flow direction were tested as
      independent variables. A multiple linear regression model was also developed for
      predicting the exact degree of carotid stenosis on angiogram. The validation set
      was then used to evaluate the accuracy of these models. RESULTS: According to the
      logistic regression strategy, the best multiple logistic regression model was as
      follows: probability of threshold carotid stenosis = exp(2.6 PSV - 6.2)/[1 +
      exp(2.6 PSV - 6.2)]. The best linear regression model was as follows: degree of
      carotid stenosis = 20.2 PSV - 7.4 EDV + 0.4 SCR + 8.5. Both models proved to be
      valid following an evaluation of the validation set. CONCLUSIONS: This study
      illustrates that Doppler parameters may be of use in predicting the exact degree
      of carotid stenosis and the probability of threshold carotid stenosis. This is
      important if duplex criteria are going to replace angiography as the only tool
      for selecting endarterectomy candidates.

PMID- 14569825
TI  - Diffusion-weighted echo-planar MRI of the brain with calculated ADCs: a useful
      tool in the differential diagnosis of tumor necrosis from abscess?
AB  - BACKGROUND AND PURPOSE: It was the aim of this study to evaluate whether brain
      abscesses could be distinguished reliably from necrotic brain tumors using
      diffusion-weighted imaging (DWI) with calculated apparent diffusion coefficients
      (ADCs). METHODS: The authors studied 27 lesions in 26 patients (21 tumors and
      metastases, 5 pyogenic brain abscesses, and 1 cerebral toxoplasmosis). DWI was
      obtained with a single-shot echo-planar imaging spin-echo sequence. ADCs were
      calculated for all images. RESULTS: ADCs (x 10(-3) mm2/s) measured in the
      necrotic parts of the tumors ranged from 2.94 (glioblastoma) to 1.51 (astrocytoma
      III). In the inflammatory lesions, ADCs ranged between 0.91 and 3.07 (cerebral
      toxoplasmosis and pyogenic abscess). The contrast-enhanced parts of the lesions
      showed ADC values from 0.77 (pyogenic abscess) up to 1.68 (glioblastoma).
      CONCLUSIONS: DWI with calculated ADC values does not allow the reliable
      differentiation of enhanced central necrotic intracranial lesions.

PMID- 14569826
TI  - Comparative evaluation of concomitant structural and functional neuroimages in
      Rasmussen's encephalitis.
AB  - BACKGROUND AND PURPOSE: Rasmussen's encephalitis (RE) is a rare condition of
      unknown cause characterized by intractable seizures, progressive hemiparesis,
      mental impairment, and inflammatory histological findings in the cortex. The
      primary diagnosis is based on biopsy to confirm the typical clinical,
      electroencephalography, and brain imaging findings. The main objective of this
      study was to compare simultaneous structural and functional neuroimages in RE.
      METHODS: Concomitant magnetic resonance imaging and 2-deoxy-2-[18F]-fluoro-D
      glucose positron emission tomography data from the authors' series of 5 children
      and 8 patients described in the literature were analyzed and compared. RESULTS:
      Typical early findings of RE include metabolic abnormalities (hypermetabolism and
      hypometabolism) starting in the frontal or temporal regions or, occasionally,
      involving the whole hemisphere. Focal abnormalities of cerebral glucose
      metabolism indicate lesions sooner and depict their extent better than
      concomitant magnetic resonance images. The major structural abnormality remains
      unilateral; however, contralateral frontal lobe hypometabolism or crossed
      cerebellar diaschisis can be a finding of this disease. Basal ganglia involvement
      and whole hemispheric metabolic abnormality appear typically only after several
      months of disease onset. CONCLUSION: Concomitant structural and functional
      neuroimaging provide possibly complementary information in the early noninvasive
      workup of RE and may facilitate the early diagnosis of this rare disorder.

PMID- 14569827
TI  - MRI features of intramedullary spinal cord ependymomas.
AB  - BACKGROUND AND PURPOSE: To assess the magnetic resonance (MR) imaging
      characteristics of spinal intramedullary ependymomas. METHODS: MR images were
      obtained from 60 patients with spinal intramedullary ependymomas. All patients
      were treated surgically, and pathological diagnoses were confirmed. MR images of
      ependymomas and associated cysts were correlated with surgical findings. RESULTS:
      Among 60 cases of intramedullary ependymomas, 39 were cervical and 11 thoracic,
      and 10 were located at the conus medullaris and filum terminale. The lesions
      measured 1 to 10 vertebral segments in length along the neuraxis, with a mean
      length of 3.7 segments. All tumors had slightly hyperintense signals on T2
      weighted MR images. Clear tumor margins were seen in 77% of patients; 75% had
      uniform contrast enhancement. Rostral and caudal cysts were seen in 90% of all
      patients; all cysts were hypointense on T1-weighted images and hyperintense on T2
      weighted images. The rostral cysts were 1 to 5 segments in length and caudal
      cysts 2 to 10 segments in length. CONCLUSION: Ependymomas occur most often at the
      upper cord rather than in the conus medullaris and filum terminale. Of the
      cervical and thoracic ependymomas, most were cellular or epithelial types.
      Papillary ependymomas occurred exclusively in the conus medullaris and filum
      terminale. Rostral and caudal cysts are frequently associated with intramedullary
      ependymomas. Clear tumor margins, more uniform enhancement, and central locations
      can help differentiate ependymomas from other intramedullary spinal cord tumors.

PMID- 14569828
TI  - Volume flow in the common carotid artery does not decrease postprandially.
AB  - BACKGROUND AND PURPOSE: A commonplace explanation for postprandial fatigue is the
      assumption of the redistribution of perfusion from the cerebral to the
      mesenterial territory. However, this assumption has never been scientifically
      proven. METHODS: Because approximately 70% of the blood flow in the common
      carotid artery (CCA) is directed to the internal carotid artery, this vessel can
      be seen as a major brain-supplying artery. Flow volume in the CCA can be measured
      by color M-mode duplex sonography. The authors investigated the flow volume rate
      in 20 healthy volunteers before and after the intake of a high-energy meal. Heart
      rate, blood pressure, and expiratory CO2 were also measured at both times.
      RESULTS: There was a significant (P = .001) increase in right, left, and net CCA
      flow volume postprandially (right: from 362.0 [interquartile range 315.5-410.5]
      to 401.5 [322.1-486.4] mL/min; left: from 384.5 [345.5-439.0] to 414.5 [357.9
      527.7] mL/min; net: from 756.0 [683.0-822.5] to 832.4 [713.7-967.26] mL/min).
      This increase was paralleled by a statistically significant increase in heart
      rate from 66 (58-70) to 76 (63-84) bpm, but without substantial correlation (r =
      0.28) with the volume flow changes. There was no correlation with any other
      tested parameter. CONCLUSIONS: The authors conclude that the assumption of global
      brain hypoperfusion in the postprandial state cannot serve as an explanation for
      postprandial fatigue.

PMID- 14569829
TI  - The positions of the patients in the diagnosis of patent foramen ovale by
      transcranial Doppler.
AB  - BACKGROUND AND PURPOSE: There is no information about the optimal position of a
      patient for the performance of a transcranial Doppler (TCD) examination to detect
      patent foramen ovale (PFO). Such information is important to improving the
      sensitivity of the test in comparison to the gold standard of transesophageal
      echocardiography (TEE). METHODS: Thirty-four patients with TEE-proved PFO were
      examined by contrast TCD. Examinations were done in both the sitting and supine
      positions in random order. RESULTS: Eight hundred ninety-two microemboli were
      recorded. Patients' positions and the sequence of testing did not affect the
      number of microemboli detected. Yet for each individual, 1 of the 2 positions was
      more sensitive. CONCLUSIONS: To improve the sensitivity of TCD in the detection
      of PFO, it is recommended, in the case of a first negative test, to change the
      patient's position for a repeated TCD examination.

PMID- 14569830
TI  - Bilateral internal carotid artery dissection mimicking inflammatory demyelinating
      disease.
AB  - BACKGROUND AND PURPOSE: Internal carotid artery (ICA) dissection (ICAD) may be
      extremely difficult to diagnose only on the basis of historical information and
      clinical signs, and even standard brain imaging (computed tomography [CT], T2
      weighted magnetic resonance imaging [MRI]) may not be sufficient to delineate the
      underlying pathology clearly, as shown in this case. METHODS: The clinical
      presentation and parenchymal lesion pattern on CT were suggestive of inflammatory
      demyelinating disease, and additional multiparametric MRI was performed. RESULTS:
      Diffusion-weighted MRI, magnetic resonance angiography, and perfusion-weighted
      MRI revealed acute ischemic lesions, bilateral ICA obstruction, and bilateral
      hypoperfusion in the middle cerebral artery territories. Bilateral ICAD was
      confirmed by Doppler and duplex ultrasound, and anticoagulation therapy was
      initiated. A follow-up examination showed recanalization of the obstructed ICAs
      and the normalization of cerebral perfusion. CONCLUSION: This case illustrates
      the importance of demonstrating the pathology and the value of multiparametric
      MRI techniques for the diagnosis and monitoring of ICAD and its hemodynamic
      consequences.

PMID- 14569831
TI  - Endovascular treatment of a left carotid artery "bowtie" pseudoaneurysm with a
      covered Wallgraft stent.
AB  - The authors present an unusual case of a young male patient with a large left
      common carotid artery pseudoaneurysm in a shape similar to that of a bowtie
      treated with a covered Wallgraft. The Wallgraft is a covered stent originally
      designed to be used in the treatment of tracheobronchial fistula and peripheral
      arterial applications. The favorable outcome of this case illustrates its
      endovascular application in nonsurgical traumatic injuries of the carotid artery.

PMID- 14569832
TI  - "Congenital" Horner's syndrome and carotid dissection.
AB  - The authors describe a child presenting with Horner's syndrome after the repeated
      application of birthing forceps to the head and neck during vaginal delivery.
      Magnetic resonance imaging and angiography confirmed that the proximal right
      internal carotid artery (ICA) showed injury caused by dissection. Carotid duplex
      and transcranial ultrasonography provided supporting evidence of distal right ICA
      occlusion with the development of intracranial collaterals. The authors interpret
      these findings to indicate that the child suffered a traumatic dissection of the
      distal right ICA to mimic "congenital" Horner's syndrome (CHS). In a review of
      English medical literature published since 1972, the authors found 70 cases of
      CHS, none of which was attributed to carotid dissection. This case demonstrates
      that carotid dissection is an underreported cause of CHS.

PMID- 14569833
TI  - Giant axonal neuropathy: MRS findings.
AB  - Giant axonal neuropathy (GAN) is a rare genetic disease of childhood involving
      the central and peripheral nervous systems. Axonal loss with several giant axons
      filled with neurofilaments is the main histopathological feature of peripheral
      nerve biopsies in this disease. Routine neuroimaging studies reveal diffuse
      hyperintensities in cerebral and cerebellar white matter. In this case report,
      the authors present the brain magnetic resonance spectroscopic features (normal N
      acetylaspartate/creatine and increased choline/creatine and myoinositol/creatine
      ratios), which might indicate the absence of neuroaxonal loss and the presence of
      significant demyelination and glial proliferation in white matter, of an 11-year
      old boy diagnosed with GAN.

PMID- 14569834
TI  - Asymmetric neuroimaging in Creutzfeldt-Jakob disease: a ruse.
AB  - Creutzfeldt-Jakob disease (CJD) causes diffuse neurological symptoms, but
      asymmetric lesions have been found on conventional magnetic resonance imaging
      (MRI) and diffusion-weighted imaging (DWI). Less often, position emission
      tomography (PET) scanning can also reveal asymmetric lesions in patients with
      CJD. Such imaging may mislead clinicians. The authors present a case of a woman
      with CJD who was diagnosed as having suffered a stroke because she had asymmetric
      T2-weighted imaging (T2WI) MRI abnormalities that were interpreted as a stroke.
      It was noted that the patient had clinical features consistent with CJD,
      including rapidly progressive dementia, myoclonus, cerebellar dysfunction, and
      pyramidal and extrapyramidal signs. This diagnosis was supported by periodic
      epileptiform discharges on the electroencephalogram (EEG) and by elevated 14-3-3
      protein in the cerebrospinal fluid. MRI T2WI and DWI showed dramatically
      asymmetric abnormalities involving the left cortex. A PET study found decreased
      metabolism in the left cerebral and right cerebellar hemispheres. The patient's
      clinical, EEG, and laboratory data were all consistent with CJD, not other
      diseases, but the MRI and PET had atypical, asymmetric findings. This case
      demonstrates that CJD should be considered in the differential diagnosis of
      patients with rapidly progressive neurological decline, even if they have
      asymmetric imaging findings.

PMID- 14569835
TI  - Is psychoanalysis in crisis? Research results.

PMID- 14569836
TI  - A brief discourse on psychotherapy and psychoanalysis: historical perspective.

PMID- 14569837
TI  - A brief discussion on frequency of sessions and its impact upon psychoanalytic
      treatment.

PMID- 14569838
TI  - A survey of clinicians' views about change in psychoanalytic practice and
      theoretical orientation.

PMID- 14569839
TI  - Death, repression, narcissism, misogyny.

PMID- 14569840
TI  - Irinotecan and other agents in upper gastrointestinal and colorectal carcinomas.
      The University of Texas M. D. Anderson Cancer Center Investigators' Workshop,
      Volume 3. Introduction.

PMID- 14569841
TI  - Irinotecan and paclitaxel in metastatic adenocarcinoma of the esophagus and
      gastric cardia.
AB  - Both irinotecan (CPT-11, Camptosar) and paclitaxel have been shown to have single
      agent activity in adenocarcinomas of the esophagus and gastric cardia. A phase I
      trial of the combination at UCLA established the dose as irinotecan at 225 mg/m2
      and paclitaxel at 100 mg/m2 every 3 weeks. Preliminary data from a phase II trial
      of this regimen in adenocarcinomas of the gastroesophageal junction show good
      tolerability and promising activity (response rate of 27%), even in previously
      treated patients.

PMID- 14569842
TI  - Irinotecan and fixed-dose-rate gemcitabine in advanced pancreatic and biliary
      cancer: phase I study.
AB  - It is a continuing challenge for oncologists to effectively treat
      advanced/metastatic pancreatic and biliary cancer. Both irinotecan (CPT-11,
      Camptosar) and gemcitabine (Gemzar) have shown activity against these diseases
      with different mechanisms. Preclinical and clinical data also suggest additive or
      synergistic effects of the combination of these two agents with few or no
      overlapping toxicities. Phosphorylation of gemcitabine, a process of
      intracellular activation of the agent, is dose-rate dependent. It has been
      suggested that the fixed-dose-rate infusion of gemcitabine increases the
      concentration of intracellular triphosphate gemcitabine, which in turn may result
      in more objective responses and longer median survival compared to the standard
      infusion. This phase I study tests the toxicity of the combination of irinotecan
      with fixed-dose-rate infusion of gemcitabine, and determines the dose of the
      combination for phase II investigation.

PMID- 14569843
TI  - Irinotecan/cisplatin followed by 5-FU/paclitaxel/radiotherapy and surgery in
      esophageal cancer.
AB  - Local-regional carcinoma of the esophagus is often diagnosed in advanced stages
      because the diagnosis is established when symptoms are severe. The prognosis of
      patients with local-regional carcinoma of the esophagus continues to be grim.
      While preoperative chemoradiotherapy increases the fraction of patients who
      achieve pathologic complete response, that percentage is approximately 25%. In an
      attempt to increase the number of patients with either no cancer in the surgical
      specimen or only microscopic cancer, we adopted a three-step strategy. The
      current study utilized up to two 6-week cycles of induction chemotherapy with
      irinotecan (CPT-11, Camptosar) and cisplatin as step 1. This was followed by
      concurrent radiotherapy and chemotherapy with continuous infusion fluorouracil (5
      FU) and paclitaxel as step 2. Once the patients recovered from chemoradiotherapy,
      a preoperative evaluation was performed and surgery was attempted. All patients
      signed an informed consent prior to their participation on the study. A total of
      43 patients were enrolled. The baseline endoscopic ultrasonography revealed that
      36 patients had a T3 tumor, five patients had a T2 tumor, and two had a T1 tumor.
      Twenty-seven patients had node-positive cancer (N1). Thirty-nine (91%) of the 43
      patients underwent surgery; all had an R0 (curative) resection. A pathologic
      complete response was noted in 12 of the 39 patients. In addition, 17 patients
      had only microscopic (< 10%) viable cancer in the specimen. Therefore, a
      significant pathologic response was seen in 29 (74%) of 39 taken to surgery or 29
      (67%) of all 43 patients enrolled on the study. With a median follow up beyond 25
      months, 20 patients remain alive and 12 patients remain free of cancer. Our
      preliminary data suggest that the proportion of patients with significant
      pathologic response can be increased by using the three-step strategy.

PMID- 14569844
TI  - Gemcitabine and irinotecan in locally advanced or metastatic biliary cancer:
      preliminary report.
AB  - Chemotherapy has had limited success in biliary tract cancer. Of the newer
      agents, gemcitabine (Gemzar) and irinotecan (CPT-11, Camptosar) both have single
      agent activity in patients with advanced disease. We conducted a phase II trial
      to study the efficacy and toxicity of the combination of gemcitabine plus
      irinotecan in patients with locally advanced or metastatic biliary tract cancer.
      The study has enrolled 14 patients with histologically or cytologically
      documented cancer of the biliary tract or gallbladder with bidimensionally
      measurable disease, Eastern Cooperative Oncology Group performance status 0 or 1,
      decompressed biliary tree, and no prior exposure to chemotherapy. Gemcitabine at
      1,000 mg/m2 and irinotecan at 100 mg/m2 were both administered on days 1 and 8,
      every 21 days. In patients who had less than grade 3 hematologic and less than
      grade 2 nonhematologic toxicity following cycle 1, the dose of irinotecan was
      increased to 115 mg/m2 for subsequent cycles. A total of 65 cycles of
      chemotherapy have been administered, with an average of 4.5 cycles per patient
      (range: 1 to 11 cycles). The median treatment duration was 3 months (range: 0.75
      to 8 months). An objective partial response was determined radiographically in
      two patients (14%) while stable disease for periods ranging from 4 to 11.5 months
      was noted in six patients (43%). Toxicity consisted of grade 3/4 neutropenia in
      seven patients (50%) with no episodes of febrile neutropenia, grade 3/4
      thrombocytopenia in four (28%), grade 3 diarrhea in two (14%), and grade 3 nausea
      in one patient. The combination of gemcitabine plus irinotecan appears to possess
      modest clinical activity, and it is well tolerated in patients with advanced
      biliary cancer. Patient accrual is ongoing to this study.

PMID- 14569845
TI  - Phase II study of docetaxel and irinotecan in metastatic or recurrent esophageal
      cancer: a preliminary report.
AB  - The outcomes for patients with metastatic or recurrent esophageal cancer are
      dismal, with 1-year survival rates of approximately 20%. In this phase II study,
      we studied the combination of docetaxel (Taxotere) and irinotecan (CPT-11,
      Camptosar) in patients with metastatic or recurrent esophageal cancer. Eligible
      patients included those with histologic or cytologic diagnosis of adenocarcinoma
      or squamous cancer of the esophagus or gastroesophageal junction who had received
      no previous chemotherapy for metastatic esophageal cancer. Previous chemotherapy
      in the neoadjuvant or adjuvant setting was allowed. Patients received irinotecan
      at 160 mg/m2 over 90 minutes followed by docetaxel at 60 mg/m2 intravenously over
      1 hour, with chemotherapy cycles repeated every 21 days. Patients were
      reevaluated every two cycles. Of a planned 40 patients, 15 were enrolled, with 14
      patients evaluable for toxicity and 10 evaluable for response and survival. The
      combination of docetaxel and irinotecan resulted in a response rate of 30%. An
      additional 40% achieved stable disease. The median survival was 130 days, with
      three patients still alive at the time of this analysis. The toxicities included
      71% incidence of grade 4 hematologic toxicities, with 43% febrile neutropenia.
      One patient died of cecal perforation after one cycle. There was no evidence of
      pharmacokinetic interaction, as systemic clearance of both drugs was similar to
      that seen after single-agent administration. In conclusion, the regimen of
      docetaxel and irinotecan is active in metastatic or recurrent esophageal cancer.
      However, this combination chemotherapy regimen has an unacceptable rate of
      febrile neutropenia. This regimen needs to be modified to reduce the incidence of
      febrile neutropenia.

PMID- 14569846
TI  - Irinotecan in esophageal cancer.
AB  - The limited effectiveness of chemotherapy in esophageal cancer used to palliate
      metastatic disease or to combine with radiotherapy in locally advanced disease
      has prompted the evaluation of new systemic agents. Irinotecan (CPT-11,
      Camptosar) has shown promising activity in a number of gastrointestinal cancers,
      including esophageal cancer. The phase II evaluation of the combination of weekly
      irinotecan and cisplatin has shown encouraging response rates exceeding 30% to
      50% in esophageal and gastric cancer. Novel regimens include the combination of
      irinotecan with mitomycin (Mutamycin), the taxanes docetaxel (Taxotere) and
      paclitaxel, and continuous infusion fluorouracil (5-FU). Irinotecan is an active
      radiosensitizer, and trials have evaluated the combination of irinotecan with
      concurrent radiotherapy. We completed a phase I trial combining weekly
      irinotecan, cisplatin, and concurrent radiotherapy in locally advanced esophageal
      cancer. Minimal toxicity has been observed, with no grade 3/4 esophagitis or
      diarrhea, and hematologic toxicity was also surprisingly minimal. Full doses of
      weekly irinotecan (65 mg/m2) and cisplatin (30 mg/m2) could be combined safely
      with concurrent radiotherapy, with a significant rate of pathologic complete
      response. Phase II evaluation of this chemoradiotherapy regimen as preoperative
      therapy is planned at single institutions and at the cooperative group level in
      the United States. Further phase I and II investigation of combined irinotecan,
      cisplatin, and concurrent radiation is ongoing with the addition of targeted
      agents, including celecoxib (Celebrex), cetuximab (Erbitux), and bevacizumab
      (Avastin). Alternative combinations of irinotecan with radiotherapy, including
      the addition of docetaxel and continuous infusion 5-FU, are also undergoing phase
      I and II evaluation.

PMID- 14569847
TI  - Improving the toxicity of irinotecan/5-FU/leucovorin: a 21-day schedule.
AB  - Irinotecan (CPT-11, Camptosar) is one of the new generation of chemotherapeutic
      agents that has activity in advanced colorectal cancer. It has antitumor efficacy
      as a single agent, and also has been combined with fluorouracil (5-FU) and
      leucovorin (IFL) to treat these patients. Randomized studies have confirmed the
      superiority of IFL to 5-FU and leucovorin alone with regard to patient survival,
      time to progression, and tumor response rate. The optimal schedule for combining
      these agents remains uncertain, but in the United States, the schedule of IFL
      weekly for 4 consecutive weeks repeated every 6 weeks, according to the schedule
      reported by Saltz et al, has been widely used, although with some toxicity
      (especially myelosuppression and diarrhea). In an attempt to improve the
      tolerability of IFL, some have advocated modifying the schedule of IFL to weekly
      for 2 weeks, with repeated cycles every 21 days. Twenty-three patients with
      advanced colorectal cancer have been treated on this schedule at a single
      institution. Therapy was well tolerated, with 35% of patients experiencing grade
      3/4 neutropenia, two of whom had episodes of febrile neutropenia, and 9% with
      grade 3/4 diarrhea. The median relative dose intensity of irinotecan administered
      in the first 18 patients treated with this regimen was 94%. These data support
      the hypothesis that modifying the schedule of administration of IFL improves the
      tolerability and ability to deliver the regimen, but must be confirmed by
      randomized prospective studies, which may also attempt to evaluate the role of
      bolus 5-FU in the treatment of advanced colorectal cancer.

PMID- 14569848
TI  - Cancer Websites you can use: people living with cancer.

PMID- 14569849
TI  - Toward a breast cancer vaccine: work in progress.
AB  - Advances in biotechnology and basic immunology have converged to create an
      unprecedented opportunity to use vaccines to harness the power of the immune
      system in the fight against breast cancer. Cancer vaccines have several
      therapeutic advantages over more traditional breast cancer treatment modalities.
      First, targeting the antitumor immune response to critical tumor-specific
      antigens defines a therapy with exquisite specificity and minimal toxicity.
      Second, immune-mediated tumor destruction occurs by mechanisms distinct from
      those underlying the efficacy of chemotherapy and hormone therapy. Thus,
      immunotherapy offers an approach to circumventing the intrinsic drug resistance
      that currently underlies therapeutic failure. Third, the phenomenon of
      immunologic memory endows immunotherapy with the potential for creating a durable
      therapeutic effect that is reactivated at the onset of disease relapse. Moreover,
      immunologic memory also underlies the potential future use of vaccines for the
      prevention of breast cancer. Early clinical trials have highlighted the promise
      of breast cancer vaccines, and have further defined the challenges facing
      translational scientists and clinical investigators. The judicious application of
      laboratory advances to clinical trial design should facilitate the development of
      immunotherapy as an additional major therapeutic modality for breast cancer, with
      the potential for breast cancer prevention as well as treatment.

PMID- 14569850
TI  - Trastuzumab/navelbine produces encouraging results in early breast cancer
      patients.

PMID- 14569851
TI  - Cervical cancer: issues of sexuality and fertility.
AB  - Cervical cancer rates have fallen in the United States; regardless, the disease
      remains a significant concern for women, especially those who are premenopausal.
      The management of cervical cancer is dependent on stage of disease at diagnosis,
      and specific needs emerge for patients both during and following treatment. Over
      the past decade, the focus has been to maintain adequate tumor control while
      reducing long-term negative consequences. However, problems with sexuality and
      fertility persist for women treated for cervical cancer despite these advances.
      Sexual dysfunction following treatment for gynecologic cancer has been well
      documented in the literature, and recent studies demonstrate the success of brief
      psychosexual interventions. Treatment of sexual difficulties in cancer patients
      can be achieved through the provision of information, support, and symptom
      management, ideally as part of a sexual health program. Resources are not always
      available to develop such a program. However, medical professionals can identify
      individuals and organizations with expertise in treating sexual and fertility
      concerns, which can be provided to their patients, making help with these
      problems more accessible as needs arise.

PMID- 14569852
TI  - Clinical trials referral resource. Current clinical trials of G3139.

PMID- 14569854
TI  - Management of mycosis fungoides. Part 1. Diagnosis, staging, and prognosis.
AB  - Mycosis fungoides is a low-grade lymphoproliferative disorder caused by CD4+
      lymphocytes. It is the most common type of cutaneous T-cell lymphoma. Typically,
      neoplastic T cells localize to the skin and produce patches, plaques, tumors, or
      erythroderma. Diagnosis of early mycosis fungoides can be difficult due to the
      nonspecific nature of cutaneous and histologic findings. However, recent advances
      in the application of histologic criteria, coupled with molecular biology tools
      such as immunophenotyping and polymerase chain reaction, have improved diagnostic
      accuracy. Independent prognostic factors include the extent and nature of skin
      involvement, the presence of extracutaneous disease, blood involvement, age > or
      = 60 years, and lactate dehydrogenase elevation. Accordingly, patients with
      limited patches and/or plaques (stage IA or IIA) experience long-term survival
      comparable to that of matched controls. The median survival is 11 years for
      patients with extensive patch/plaque (stage IB or IIA), 3.2 years for those with
      cutaneous tumors (stage IIB), 4.6 years for those with erythroderma (stage III),
      1.2 years for those with pathologic nodal involvement (stage IVA), and 0.9 years
      for those with visceral disease (stage IVB). Over time, mycosis fungoides may
      progress to Sezary syndrome or transform to large-cell histology.

PMID- 14569853
TI  - Bisphosphonates in the prevention and treatment of bone metastases.
AB  - Bisphosphonates have an established role in treating tumor-induced hypercalcemia
      and decreasing the incidence of skeletal-related events. Recent data suggest that
      these agents may also prevent skeletal metastases. This review explains how
      cancer metastasizes to bone and how bisphosphonates may block this process, with
      a summary of clinical trials supporting the use of bisphosphonates to treat and
      prevent bone metastases. For skeletal metastases in patients with breast cancer,
      multiple myeloma, or other solid tumors, bisphosphonates are important adjuncts
      to systemic therapy. Despite promising results in metastatic prostate cancer,
      additional trials are needed before bisphosphonates become part of standard
      treatment in this setting. Ongoing trials are evaluating the preventive role of
      the third-generation bisphosphonates in breast cancer patients. Until the results
      of these trials are presented, bisphosphonates should only become a component of
      adjuvant treatment in the context of a clinical trial. Bone loss, a common
      consequence of cancer treatment, should be treated with the usual measures
      indicated for the management of osteoporosis, including bisphosphonates.

PMID- 14569855
TI  - Evolution of AO philosophy.

PMID- 14569856
TI  - 40-year experience in surgical treatment of congenital chest deformations-
      ethiopathogenesis, operative techniques and clinical results.
AB  - PURPOSE OF THE STUDY: The aim of this study was to assess the results of surgical
      treatment of 58 patients with pectus excavatum and 11 with pectus carinatum and
      discuss the problems connected with ethiopathogenesis and operative techniques.
      MATERIAL: 69 chest deformations treated between 1961-2001. METHODS: The clinical
      results were analyzed with 1) Kopera-Krol Rtg-index, 2) Gizycka's Rtg-index of
      chest flattening, 3) Haller and Nakahara CT-index, 4) Heart position after
      operation, 5) Frequency of upper respiratory infections, 6) Appearance of
      postoperative scar, 7) Patient's opinion. Histopathological investigations were
      used to assess ethiopathogenesis of chest deformations. RESULTS: 90% permanent
      correction achieved in group of patients operated in the age from 12 to 17.
      Otherwise we noted between the patients who were operated in the age from 6 to 10
      37% recurrence of deformity. Generally we had 70% excellent and good results. The
      opinion of patients (including cosmetics effects, psychical state and exercise
      tolerance) was much better-86.6%. Particularly correction of pectus carinatum
      gives good cosmetics effects as well as improvement of exercise tolerance.
      DISCUSSION: Nuss modified correction employing a substernal stabilizing plate is
      an alternative for transsternal traction in the classical Ravitsch' procedure.
      Authors present advantages and disadvantages of both methods. The optimal age for
      surgical correction and inter and post operative procedure are discussed.
      CONCLUSIONS: Ethipathogenesis of pectus excavatum and carinatum remains
      unsettled. Disturbances in endochondral ossification and growth of costal
      cartilage seem to be more probable cause of the deformities than diaphragm
      underdevelopment. Mild and severe forms of the two deformities result in
      circulatory-respiratory malfunctions, cosmetic defects and psychical problems.
      Due to possible circulatory-respiratory disorder, appropriate premedication as
      well as intra- and postoperative monitoring of RR, ECG, O2, CO2 are very
      important on the first day after the surgery. Ravistch-Garnier procedure for
      pectus excavatum and Chen procedure for pectus carinatum remain operations of
      choice. Transsternal traction can be replaced with internal stabilisation with a
      bar placed under the sternum what considerably reduces the time of
      hospitalisation but requires one more hospitalisation to remove the bar.
      Correction of pectus carinatum is permanent, correction of pectus excavatum
      turned out to be permanent in 90% cases providing that they were performed in
      patients aged 12-16. When patients were at the age 6-10, recurrence of the
      deformity occurred in 37% of cases. According to the clinical assessment, in both
      age groups, the proportion of very good or good scores equalled 70% and according
      to patient's evaluation--86.6%.

PMID- 14569857
TI  - [Traumatic spondylolisthesis of the axis].
AB  - PURPOSE OF THE STUDY: The study presents a group of patients with traumatic
      spondylolisthesis of the axis. Views on the treatment of different types of
      spondylolisthesis vary. The aim of this study was to carry out a retrospective
      evaluation of the group of patients with this traumatic condition. MATERIAL: In
      the period from 1995 to 2002, 26 patients with traumatic spondylolisthesis of the
      axis were treated. They accounted for 5% of all patients admitted to our
      department for cervical spine injuries. Three types of traumatic
      spondylolisthesis were distinguished according to the Effendi classification.
      Type I was diagnosed in seven, type II in 18 patients and type III in one
      patients. METHODS: Type I traumatic spondylolisthesis was, as a rule, treated
      conservatively. A halo vest was used in four and a Philadelphia collar in three
      patients. Patients diagnosed with type II spondylolisthesis were treated
      surgically from the anterior approach (16 patients) or with a halo vest (two
      patients). The only patient with a type III fracture was operated on from the
      anterior approach. RESULTS: Osseous healing was achieved in all patients. No
      pseudoarthrosis developed and no repeat surgery for infection or osteosynthesis
      failure was needed. No deterioration of neurological findings was recorded. The
      range of motion in the cervical spine after healing was not affected. DISCUSSION:
      Views on the classification and therapy of traumatic spondylolisthesis of the
      axis are diverse. The greatest diversity is associated with making a decision on
      whether the injury is unstable and requires surgical treatment or not. Further
      arguments are related to the use of the most suitable approach. Treatment from
      the anterior approach is prevailing. Type III fractures are rare and must always
      be treated surgically. CONCLUSIONS: Methods for treatment of traumatic
      spondylolisthesis of the axis are currently a topic of dispute. The decisive
      factor for therapy is whether the injury is stable or unstable. When instability
      is present, anterior C2-3 spondylodesis completed with plate osteosynthesis is
      the method of choice. Stable injuries are treated by the application of a halo
      vest or Philadelphia collar.

PMID- 14569858
TI  - [Current diagnostic and therapeutic approaches in liver injuries].
AB  - PURPOSE OF THE STUDY: The recent improvements in hospital care system
      (centralized specialized care) and the use of new imaging methods and modern
      technologies in surgical treatment have greatly enhanced successful outcomes of
      therapy in liver injury. The aim of the study was to evaluate the contribution of
      procedures included in the diagnostic-therapeutic algorithms to the treatment of
      blunt injury to the liver in our patient population. MATERIAL: Our group
      consisted of 43 patients with blunt injury to the liver who were treated at the
      Emergency Department between 1998 and 2002. In 28 patients, blunt injury was part
      of polytrauma, in 7 patients it was associated with thoraco-abdominal injury and,
      in 8 patients, it was the only trauma sustained. METHODS: The diagnosis and
      therapy were based on the algorithm currently used for treating liver injury at
      the Emergency Department. In addition to clinical examination and assessment of
      the actual status of hemodynamics, spinal computed tomography was carried out to
      establish the therapeutic procedure. Fourteen patients were treated
      conservatively according to the criteria of a non-surgical approach and 29
      patients underwent urgent surgery. Indications for revision surgery included,
      apart from signs of ongoing abdominal bleeding related to liver injury, combined
      spleen and kidney trauma. All patients with thoraco-abdominal involvement had
      laparotomy; in addition, four underwent thoracotomy including repair of the
      lacerated lung by suturing and three patients required suturing of a rupture of
      the right part of the diaphragm. RESULTS: In the patients treated conservatively,
      10 showed spontaneous regression of parenchymal hematomas and four had to be
      treated by suction drainage. Out of 29 patients operated on, five died with signs
      of an irreversible hemorrhagic shock from multiple trauma and one died of
      multiple organ failure. DISCUSSION: The principal criterion determining therapy
      in blunt liver injury is the patient's hemodynamic status; laparotomy is
      mandatory in intra-abdominal trauma with severe hemoperitoneum or when unstable
      hemodynamics is due to intraperitoneal bleeding. Non-surgical treatment of blunt
      liver injury, on condition that the established criteria are observed, has
      several advantages such as less stress for the patient, fewer intra-abdominal
      complications and fewer blood transfusions needed. The modern technologies used
      in the operative procedure are related to both a transient vascular occlusion and
      a strategy for selective care in liver trauma. CONCLUSION: 1. The treatment
      strategy in a patient with blunt liver trauma is determined by the patient's
      hemodynamic status; in a stable patient, spinal CT examination of the thorax and
      abdomen is mandatory. 2. Urgent laparotomy is indicated when the patient with
      blunt liver trauma is hemodynamically unstable due to diagnosed hemoperitoneum or
      suspected intraperitoneal bleeding. 3. Conservative therapy is applied when the
      criteria for non-surgical treatment are fulfilled. 4. Surgical strategy for blunt
      liver trauma is based on the extent and localization of the injury, the patient's
      overall status and severity of associated injuries. Resection of the injured
      parenchyma is indicated when laceration of a liver lobe occurs. 5. The prognosis
      of blunt liver injury is influenced, apart from hemorrhagic shock reversibility,
      by the severity of associated injuries in multiple trauma.

PMID- 14569859
TI  - [Injuries of the lower cervical vertebrae--the monocortical stabilization
      technique].
AB  - PURPOSE OF THE STUDY: In contrast to the thoracolumbal spine, the cervical spine
      bears a lower biomechanical load and, therefore, anterior stabilization of a
      fracture is a definitive procedure in the majority of cases. What remains the
      matter of choice is screw fixation in the body of the vertebra involved. This may
      be either monocortical or bicortical. In this study, we evaluate a group of
      patients in whom fractures of the lower cervical spine were treated using the
      CSLP monocortical system (Synthes). MATERIAL: We included 68 patients in whom
      complete radiographic data were available and the surgery was performed more than
      6 months earlier. This group comprised 49 men and 19 women with the mean age of
      37.6 years and range of 12 to 79 years. In the first stage, all patients were
      operated on from the anterior approach. In 11 (16.2%) patients with type B or C
      injury, according to the AO classification, the procedure was completed by dorsal
      stabilization. The definite indication for surgery was any involvement of nerve
      structures or open fractures; kyphosis greater than 15 degrees, reduction by more
      that 50% of the proximal edge of the vertebral body, narrowing of the spinal
      canal by more than 50%, multiple wedge fractures and disc and ligament injuries
      associated with instability were considered conditional indications. METHODS: Any
      locked dislocation was reduced manually under X-ray guidance in the shortest
      possible time. Subluxations or fractures of the vertebral body were reduced by
      positioning the patient's body on the operating table. The standard procedure for
      subluxation management was distraction of the segment by applying a Caspar's
      distractor and subsequent microscopic discectomy up to the posterior longitudinal
      ligament. A tricortical bone graft was collected from the iliac crest. After its
      implantation, the distractor was released and the segment was fixed by a CSLP
      system (Synthes) with monocortical screws 14 mm long, usually used in a 2 + 2
      configuration. In locked dislocation, in addition, the discission of the
      posterior longitudinal ligament and inspection of the dural sac were performed,
      and completed by dorsal stabilization with hook plates or a Cervifix fixator
      (Synthes) in one procedure under anesthesia. When the body of the vertebra was
      fractured, either partial or subtotal excision of it was carried out according to
      the type of fracture or when displaced fragments protruded into the spinal canal.
      A tricortical graft taken from the iliac crest was larger than in the treatment
      of subluxation but a plate was applied as in monosegmental fixation. In addition,
      the graft was fixed with special screws that had a porous surface and holes in
      the shank. Dorsal stabilization with hook plates or a Cervifix fixator was used
      for severe instability in type B or C injury. RESULTS: The normal range of
      cervical spine motion (flexion, extension, inclination, rotation) was found in 44
      patients. Slightly limited movement (75% to 90% normal motion) was in 17 patients
      and seven were affected more seriously (50% to 75% normal motion). Of the 19
      patients with neurological deficit, 13 showed improvement by 1, 2 or 3 grades of
      Frankel's classification in seven, four and two patients, respectively. The first
      signs of bone remodeling between the graft and covering plate, usually at the
      distal graft border, were found in 16 patients at 6 weeks and in the remaining 52
      patients at 12 weeks. By 6 months postoperatively, all patients showed complete
      healing and incorporation of the tricortical graft. The cranial screws broke in
      one case (1.5%) but this had no effect on the treatment outcome. No complication
      related to the surgical procedure occurred intraoperatively. DISCUSSION: The very
      good results achieved with the use of the CSLP monocortical system in this study
      (98.5% fusion without broken screws or plates) are in agreement with relevant
      data reported in the Czech and foreign literature. The principal condition is a
      careful preparation of both the endplates of vertebral bodies and the graft.
      After insertion, this should stay in place without any tendency to extrude. If
      the graft is too long, it imposes an increased load on plates or screws that
      consequently act ventrally. CONCLUSION: Our experience and literature data
      suggest that the CSLP monocortical system is fully capable to stabilize the lower
      cervical spine after injury, supposing all procedures described above are
      completed. In more serious trauma and type B or C instability, the additional
      dorsal instrumented fusion is indicated.

PMID- 14569860
TI  - [Arthroscopic stabilization of the shoulder using anchors].
AB  - PURPOSE OF THE STUDY: The purpose of the current report was to present our
      initial experience with an arthroscopic technique for anterior stabilization of
      the shoulder with an anchor in 64 patients who had recurrent anterior
      glenohumeral instability. MATERIAL: The application of arthroscopic techniques
      for the operative treatment of recurrent anterior instability of the glenohumeral
      joint has generated widespread interest. The goal of all arthroscopic techniques
      for stabilization of the shoulder is the re-establishment of a functioning
      inferior glenohumeral ligament. This is achieved by reattaching the avulsed
      anteroinferior aspect of the labrum or capsule to the anterior aspect of the
      glenoid neck with one of a variety of methods. Arthroscopically assisted repair
      of the anterior aspect of the labrum with use of a bioabsorbable/nonabsorbable
      suture with an anchor was performed in 64 consecutive patients who had chronic
      anterior instability of the shoulder. The average age of the patients was twenty
      seven years (range, sixteen to fifty-two years). The etiology of the instability
      was a traumatic injury in 53 patients. All fifty-three shoulders had a Bankart
      lesion. The patients were evaluated at an average of 18 months (range, 3 to 36
      months) after the procedure. METHODS: During shoulder arthroscopy in typical
      laying position with traction applied on upper extremity we made diagnosis of
      capsule defect or laxity in all the cases. Using anchor technique we sutured
      capsule defect, or tightened loose capsule to glenoid rim. Two or three sutures
      were used. The anchors were Mitek GII implants, or Arthrex screws, with non
      absorbable sutures in most cases. RESULTS: Fifty (78 per cent) of the patients
      were asymptomatic and were able to participate in sports without restriction. The
      repair was considered to have failed in three (4.5 per cent) of the patients. In
      one of them, the failure resulted from a single traumatic reinjury during
      participation in a contact sport, and was treated operatively. The remaining two
      failures occurred atraumatically. DISCUSSION: It is difficult to compare the
      results from the present study with those from other reports on arthroscopic
      techniques of anterior stabilization because of variation among the indications,
      the techniques, and the implants that were used. The degree of capsular laxity is
      central to the success or failure of arthroscopic stabilization. CONCLUSION:
      Anterior stabilization of the shoulder with an anchor may be indicated for
      patients who have anterior instability with or without Bankart lesion and need
      suture of the lesion and capsulorrhaphy or capsular imbrication to reduce the
      joint volume.

PMID- 14569861
TI  - [Causes of development of genu recurvatum after surgical treatment in spastic
      forms of childhood cerebral palsy].
AB  - PURPOSE OF THE STUDY: To evaluate the contribution of different surgical
      techniques of lengthening of distal hamstrings on the development of
      hyperextension deformity of the knee in spastics. MATERIAL: Totally 51 patients
      of age 7.6 + 3.7 years at operation. Follow-up after surgical release for 4-10
      years. Basically two surgical techniques were used: 1. Simple division of
      gracilis and semitendinosus, fractional lengthening of semimembranosus and biceps
      femoris. 2. Gracilis and semitendinosus were anchored after its transverse
      division to fractionally lengthened semimembranosus. METHODS: Pre-operative and
      post-operative Bleck popliteal angles were estimated. Hyperextension was tested
      in lying and standing positions. RESULTS: Type of surgery (1 or 2) did not
      influence the development of hyperextension deformity of the knee (tested by
      Fisher exact test). Nevertheless the relation between type of surgery (1 or 2)
      and the stratified value of Bleck popliteal angle was statistically significant.
      In the subgroup 2, in which the superficial tendons were anchored to
      semimebraneous, the occurrence of values of Bleck angle less than 20 degrees, was
      lower than in the subgroup 1. DISCUSSION: It seems, that the type of described
      two different surgical techniques is not so much decisive for development of
      hyperextension deformity. CONCLUSION: Authors surmise, that principal role play
      stronger deep knee flexors (semimembranosus and biceps femoris). Its fractional
      lengthening must be very careful.

PMID- 14569862
TI  - [Surgical treatment of multiple epiphyseal dysplasia in the hip joints in
      childhood--short-term results].
AB  - PURPOSE OF THE STUDY: The presentation of our results of surgical treatment of
      the hip joints affected by multiple epiphyseal dysplasia, using the Steel
      technique of triple osteotomy of the innominate bone in children. MATERIAL:
      Twelve hip joints in 11 patients were treated by the Steel technique of triple
      osteotomy of the innominate bone at our department in the period from 2000 to
      2001. However, the evaluation involved only children who also had multiple
      epiphyseal dysplasia, i.e., two boys and one girl. One of the boys had bilateral
      surgery with 6.5 months between the operations. The average age at the time of
      operation was 7.5 years, with a range of 6.5 to 8.5 years. The indication for the
      Steel osteotomy included severe conditions characterized by flattening and
      fragmentation of the proximal femoral epiphysis that was insufficiently covered
      by a dysplastic acetabulum. METHODS: The clinical evaluation was based on a
      classification system according to Merle d'Aubigne and Postel. Assessment was
      made on X-ray films before and after surgery. The follow-up was 17 to 29 months
      with an average of 2 years. RESULTS: The average Merle d'Aubigne and Postel score
      for the operated-on hips was 17.5 points. The maximum attainable value is 18
      points; therefore all hips showed excellent clinical outcomes. Radiological
      examination showed an improvement in Wiberg's center-edge (CE) angle, i.e., from
      15 degrees preoperatively to 44 degrees postoperatively (range, 10 to 25 and 41
      to 48 degrees, respectively). The surgical treatment resulted in an average
      increase in the CE angle by 29 degrees, with the range between 21 and 33 degrees
      according to correction extent. DISCUSSION: A comparison of our results with
      those of other authors was not possible since no literature data were available
      on the Steel osteotomy in patients with multiple epiphyseal dysplasia. In our
      opinion these children constitute a specific category of patients with this
      disorder but the size of our group was too small to draw conclusions with a more
      general validity. CONCLUSIONS: The Steel triple osteotomy of the innominate bone
      permits correction of abnormal anatomical conditions of hip joints in severe
      multiple epiphyseal dysplasia. The nature of this disorder, however, requires a
      long-term follow-up of the patients treated.

PMID- 14569863
TI  - [Changes in the articular compartment in advanced osteoarthritis].
AB  - PURPOSE OF THE STUDY: Both synovial and bone forms of osteoarthritis (OA) are
      characterized by inflammatory processes in the articular compartment. Increasing
      evidence suggests that changes in bone tissue are important for the deterioration
      or loss of joint function. Therefore it is reasonable to shift emphasis from
      research on cartilage to that on other articular tissues, particularly on
      subchondral bone. The aim of the study was to demonstrate the involvement of
      several cytokines in OA development and, on the basis of changes of joint
      markers, to assess the extent of inflammatory process. MATERIAL: A total of 60
      patients with an osseous form of osteoarthritis of the knee joint (28 patients)
      or the hip joining (32 patients) underwent total knee or hip arthroplasty. The
      mean age of our patients was 66.7 +/- 10.4 years. Preoperative clinical and
      radiographic examinations were carried out as well as routine laboratory tests on
      blood and urine. Samples of urine, blood serum (BS) and synovial fluid (SF),
      extracts from cartilage (CA) and synovial membrane (SM) and granulation bone
      tissue were analysed for markers indicating the presence of inflammatory
      processes in joints. METHOD: The following markers of inflammatory activity in
      the bone compartment were investigated: pyridinoline (PYR), deoxypyridinoline (D
      PYR), bone alkaline phosphatase (BAP) and chondrex (CHON). The levels of
      cytokines IL-1 alpha, IL-8, IL-10 and TNF-alpha were assayed by immunoanalysis
      (ELISA and IMMULITE system) in BS, CA, SM, GT and SF. The tissue samples were
      obtained during arthroplasty. RESULTS: In the patients with osteoarthritis, the
      urinary levels of PYR and D-PYR were higher than control values (70.33 +/- 34.93
      vs (41.6 +/- 10.6 nmol/mmol creatinine). No significant differences were found
      between pre- and post-operative levels. Similarly, the serum levels of BAP and
      CHON compared with control values were higher (27.65 +/- 12.21 vs 12.2 +/- 2.7
      U/L and (96.35 +/- 58.83 vs 43.2 +/- 14.5 ng/ml, respectively). In all articular
      compartments and in synovial fluid, the level of cytokine IL-8 exceeded
      concentrations of the other cytokines. In blood serum, only IL-10 levels were
      markedly increased as against the control group (17.35 +/- 5.82 vs 9.80 +/- 4.40
      pg/ml). DISCUSSION: Primary osteoarthritis is the most common joint disease that
      deteriorates with age. Its symptoms are pain and a lower range of motion in the
      joint affected. The initial involvement of articular cartilage progresses to
      degenerative changes involving synovial and bony structures. This degenerative
      disease gradually develops into an inflammatory disease. At this stage, osseous
      tissue shows an increase in metabolism and bone destruction results. In the
      control of inflammatory reactions by the immune system, cytokines, among other
      proteins, play an important role: some may enhance inflammation by activating
      leukocytes (IL-1, TNF-alpha, IL-8) while others, such as IL-10, have anti
      inflammatory effects. CONCLUSION: During osteoarthritis, the articular
      compartment shows high metabolic processes that, in some patients, may increase
      and even persist some time after arthroplasty.

PMID- 14569864
TI  - [Primary bone hyperparathyroidism].
AB  - The authors report the case of a 19-year-old girl with osteolytic bone lesions in
      whom primary hyperparathyreoidism caused by parathyroid gland adenoma was
      diagnosed. They emphasize necessity to be aware of a relationship of this rare
      condition to bone lesions that may be benign in appearance and may show ambiguous
      histological findings. The patient underwent excision of the adenoma and
      subsequent substitution therapy, which resulted in the healing of bone lesions.

PMID- 14569865
TI  - [Early proteomics in ovarian cancer: myth or reality?].
AB  - Literature data summarizing new approaches and importance of early ovary cancer
      diagnostics have been reviewed. Alpha-feta-protein (AFP) and SA125 were the most
      reliable markers for determination of early ovary cancer stages. Nevertheless,
      these markers don't reflect the disease stage, malignance and they don't possess
      sufficient specificity. New methodical approaches have recently been introduced.
      They include combination of 2-D electrophoresis with mass-spectrometry. These
      methods allow to inventory and identify almost all proteins of various tissues.
      Using these methods for scanning proteins from biopsies of ovary cancer tissues
      new markers have been discovered.

PMID- 14569866
TI  - [Angiotensin-converting enzyme-2 and collectrin--recently discovered homologs of
      angiotensin-transforming enzyme].

PMID- 14569869
TI  - [Nitric oxide production in pregnancy and experimental acute kidney
      insufficiency].
AB  - Nitric oxide production in organs of pregnant mice (liver, kidney, placenta) was
      measured using specifical NO traps, Fe-dithiocarbamate complexes (Fe-DETC)
      forming with NO paramagnetic mononitrosyl iron complexes with DETC (MNIC-DETC),
      detected by EPR method (-196 degrees C). The amount of NO formed increased in
      dependence of the pregnancy period (from the first to the third trimesters).
      Addition of NO-synthase substrate, L-arginine, insignificantly influenced
      endogenous NO production. However, endogenous NO amount sharply decreased at
      experimental acute renal failure.

PMID- 14569870
TI  - [Experimental study of the effect of sodium nitrate on the functional neutrophil
      and macrophage activity].
AB  - The impact of sodium nitrite on functional activity of macrophages and
      neutrophiles of the abdominal cavity and blood of mice BALB/c was investigated in
      vitro and in vivo experiments. Functional activity was estimated according to
      formation of oxygen active forms. It was shown that sodium nitrite significantly
      inhibits formation of reactive oxygen species released from mouse peritoneal
      neutrophiles and macrophages, when they are being activated in vitro. Sodium
      nitrite was given in water at concentration 500.0 mg/l mice for 210 days
      immunodepression action was revealed which expressed reduction by leukopoes and
      decrease functional activity of blood neutrophils. Under the same conditions
      nitrite did not effect on functional activity of resident peritoneal macrophages.

PMID- 14569871
TI  - [Activity and induction of CYP2B, CYP2C, and CYP3A in tissues of cyclophosphane
      sensitive and resistant neoplasms and the liver of neoplasm-carrying mice].
AB  - The activities of three cytochrome P450 families involved in metabolic
      transformation of cyclophosphamide (CP) (CYP2B and CYP2C responsible for
      metabolic activation of CP and CYP3A responsible for inactivation of CP) have
      been investigated in lymphosarcoma and liver microsomes of tumor-bearing CBA
      mice. Two strains of mouse lymphosarcoma distinguished by their sensitivity to
      cytostatic action of CP were used in this study for implantation in mice femur
      muscle. There was certain relationship between CP resistance of lymphosarcoma and
      tumor P450s activity. CYP2B, CYP2C and CYP3A activities in the CP sensitive tumor
      were comparable to those in liver, and CYP2B, CYP2C were induced by phenobarbital
      and dexamethasone. CYP2B and CYP2C in the CP resistant tumor were inactive and
      only slightly induced by dexamethasone. CYP3A activity was lower than in LS tumor
      and unchanged during drug treatment. Implantation of LS and RLS tumor in mice
      caused different effects on P450 activities. LS insignificantly influenced liver
      CYP2B, CYP2C and CYP3A activities and their inducibility by phenobarbital and
      dexamethasone was similar to that obtained in liver of mice without tumor. At the
      same time, CYP2B and CYP2C activity in liver of RLS-bearing mice were essentially
      reduced, the activity CYP3A remained unchanged, and inducibility of CYP2B, CYP2C
      and CYP3A by phenobarbital and dexamethasone was similar to that in liver of mice
      without tumor. These results prove the role of cytochromes P450 activating CP in
      formation drug resistant phenotype of mice lymphosarcoma and suggest possibility
      of overcoming of this resistance using cytochrome P450 inducers.

PMID- 14569872
TI  - [TNF-induced apoptosis and necrosis in myeloleukemia cells HL-60 is regulated by
      reactive oxygen metabolites depending on a cell cycle phase].
AB  - TNF is the known death receptor ligand which induce apoptosis and necrosis.
      Reactive oxygen metabolites, ceramide (synthesized de novo and as a product of
      sphingomyelin cycle), and caspases have been implicated as potential mediators of
      cell death. Their mechanistic relationship remains to be elucidated. The presence
      and activation of executor caspase-3 has been found to be regulated during both
      TNF-induced apoptosis and necrosis on their early stages. TNF-induced cell
      damage, suggesting the induction of both, apoptosis and necrosis, depended on the
      cell cycle. Necrosis induced by TNF was inhibited by denitrophenol (DNP).
      Pretreatment of these cells with exogenous bacterial sphingomyelinase (SMase)
      potentiates TNF-alpha induced apoptosis only, suggesting the role of ceramide
      from sphingomyelin cycle in TNF signaling pathways of apoptosis. DNP was found to
      initiate necrosis after SMase and TNF common action. The role of ceramide
      synthesis in enhanced ceramide generation in response to oxidant stress was shown
      using inhibitor of ceramide synthase--fumonisin B1. Its effect was found to be
      modulated by mitochondrial chain respiration inhibitors. Monoclonal antibodies to
      TNF-alpha receptors R1 and R2 exhibit the more high level of necrosis compared
      with TNF and both regulated by DNP and phospholipase A2. TNF-R2 effect was not
      found previously. CONCLUSION: Ceramide synthesis and sphingomyelin breakdown,
      caspase activation and reactive oxygen metabolites production are required for
      the TNF-alpha-induced apoptosis and necrosis which may be regulated dependently
      on cell cycle. TNF-initiated necrosis seems to be the disrupted apoptotic program
      and may be classified as aponecrosis.

PMID- 14569873
TI  - [Structural and functional characteristics of insulin and mechanism of its
      effect].
AB  - On the basis of analysis of own and literature data on insulin-receptor
      interaction two centers responsible for receptor binding were identified on 3D
      structure of insulin with receptor. Two extracellular domains of insulin receptor
      interact with these centers on insulin molecule. The comparative analysis of
      primary structures of the protein disulfide isomerase thioredoxine domains and C
      terminal domain of the receptor suggests existence of the thioredoxine domain in
      the insulin receptor. In this connection the role of the thiol disulfide an
      exchange reaction is discussed in terms of insulin interaction with receptor
      followed by subsequent conformational changes in the receptor molecule and
      activation of the intercellular tyrosine kinase domain. It is supposed, that
      besides known mechanism of receptor mediated insulin signal transduction and
      tyrosine kinase activation, there is other mechanism of insulin intracellular
      signal transduction realised via cytosolic insulin-binding proteins. Major
      components of intercellular insulin signal transduction include: protein
      disulfide isomerase and insulin degrading enzyme. The importance of change of the
      intracellular insulin degradation rate for insulin signal transduction is
      discussed.

PMID- 14569874
TI  - [Modification of the method of trypsin esterase activity determination].
AB  - Determination of esterase activity of trypsin in blood serum using the Erlanger's
      method leads to overestimation of enzyme activity due to the increased "dimness"
      of the reaction medium. V. A. Shaternikov suggested a correction, which is based
      on the use of the two-wavelength registration method. But this correction does
      not eliminate this secondary factor completely. So for the clearing of the
      solutions we offer to stop the reaction by putting tubes into ice followed by
      subsequent centrifugation the investigated samples at 0 degree C for 15 min, at
      25,000 g. It gives the possibility to measure an actual increase of an optical
      density in accordance to the hydrolysis of the substrate. The results of the
      measuring of an esterase activity of trypsin are represented in a serum and in a
      peritoneal exudate of dogs with an acute experimental pancreatitis. The serum
      esterase activity of trypsin in a was not found in intact animals. Three hours
      after induction of pancreatitis trypsin activity was detected only in blood serum
      of two of seven animals [approximately 3.6 mmole/(min-l)]. Rats with acute
      pancreatitis also had very low esterase activity of trypsin in blood [0.38 +/-
      0.16 mmole/(min-l)] that insignificantly deferred from the control. These data
      question applicability of this method for diagnostics of acute pancreatitis. The
      estarse activity of trypsin detected in blood and peritoneal exudate, does not
      indicate its proteolytic activity, because it was insensitive to soybean trypsin
      inhibitor.

PMID- 14569875
TI  - [Lanthanide fluorescent immune analysis for determination of hormone thyroxine in
      dry blood spots].
AB  - The determination of thyroxin (T4) is a basic confirmative test for congenital
      hypothyroidism. 70% cases of this period inborn  disease are taking asymptomatic
      course. We developed immunofluorescent T4-assay in dried blood spots with anti-T4
      monoclonal antibody and europium chelate (dianhydride of
      diethylentriaminipentaacetic acid (DA-DTPA)). This method requires DELFIA Plate
      Fluorometer 1232 (Wallac, Finland) or its sub modifications. Panel of monoclonal
      antibodies for T4 has been obtained. Type/subtype (IgG2b, IgG1), affinity
      constants (10(7)-10(8) M-1), cross reactivity to homologous structures (0-2%)
      were determined. Stable clones with high affinity and viability were selected for
      the development of the assay. Conjugates of thyroxin and europium chelate were
      synthesized. Inclusion of sodium salicylate (2 mg/ml) and EDTA (2 mM) into the
      buffer reduced the nonspecific signal. Limit for T4 detection (T4 standarts) was
      10 nM with not more than 15% variation coefficient. Accuracy was estimated by Bio
      Rad Lipochek Immunoassay Plus Control Kit. Obtained results were within control
      confidence interval.

PMID- 14569876
TI  - [Determination of antibodies to opiate receptors by latex agglutination and
      immunoenzyme analysis].
AB  - Adsorption ability of few kinds of latex covered by synthetic peptide fragments
      of mu- and delta-opiate receptors (OR) is investigated. The levels of
      autoantibodies to opiate receptors fragments in the blood serum of patients with
      drug abuse are detected by latex agglutination and ELISA. The patients with drug
      abuse demonstrated positive latex agglutination reaction for level specific
      antibodies from 10.4 mg/ml and higher in the 71.4% of cases. The levels of
      autoantibodies to OR in the blood of patients with drug abuse was in 2.8 times
      higher of control data. The correlation between levels of autoantibodies to
      opiate receptors obtained by methods of latex agglutination and ELISA is
      revealed. The obtained data confirms our hypothesis concerning existence of
      specific changes in immune system linked with some CNS disorders like drug abuse.
      Thus, the level of autoantibodies to opiate receptors could be used as new
      criterion for diagnostics of opiate abuse.

PMID- 14569877
TI  - [Various aspects of diagnosis of food intolerance].
AB  - In the presence of food antigenes causing food intolerance in patients
      granulocytes isolated from these patients exhibited altered oxidative metabolism.
      This phenomenon may be used for diagnostics of food intolerance in vitro.

PMID- 14569878
TI  - [2-Amino-2-thiazoline derivatives--a novel chemotype possessing muscarinomimetic
      effect].
AB  - Derivatives of 2-amino-2-thiazoline exhibit muscarinomimetic properties in model
      experiments with isolated rat ileum. The activity of compounds strongly depends
      on the nature of substituents in 5-position of thiazoline ring. The most active
      spasmogenic compound is 5-iodomethyl-2-amino-2-thiazoline hydroiodide (EC50 = 13
      +/- 2 microM). Its effect is very similar to activity of cholinergic agent
      pilocarpine (EC50 = 14 +/- 4 microM), but "intrinsic activity" parameter a (alpha
      = 0.87 +/- 0.12) of 5-iodomethyl-2-amino-2-thiazoline was more significant. Ileum
      contractions induced by this compounds were inhibited by atropine. Derivatives of
      2-amino-2-thiazoline (like pilocarpine) were not demonstrated nicotinomimetic
      properties. These compounds demonstrate very weak anti-AChE activity. For 5
      iodomethyl-2-amino-2-thiazoline hydroiodide the IC50 value is 0.39 +/- 0.09 mM.

PMID- 14569879
TI  - [Intermolecular interactions of dipeptide triterpene derivatives and natural
      quinones with alpha-tocopherol].
AB  - In modeling system of the initiated oxidation of methyl oleate the antioxidation
      activity of a series of dipeptide derivatives of betulonic and glycyrrhetic
      acids, natural quinones (ubiquinone, philloquinone and menadione) and the kinetic
      effects of their combined action with alpha-tocopherol were studied. The same
      extreme character of the dependence of inhibitory action on the concentration of
      all investigated substances was found. Combined addition of triterpenoids or
      quinones together with alpha-tocopherol attenuated their effect. The mechanism of
      intermolecular interactions of tocopherol with quinones and triterpenoids is
      offered. The biological importance of these effects is discussed.

PMID- 14569880
TI  - [Combined therapy of chronic hepatitis C in children with phosphogliv].
AB  - Two schemes of the treatment of chronic hepatitis C were compared. Each scheme
      included 40 medical treatment for 2 months. 22 patients received basic therapy
      including phosphogliv, 3-5 procedures of ultraviolet irradiation of blood (UVIB)
      and referon (the course was begun after the 2-nd procedure of UVIB). 18 patients
      received basic therapy with phosphogliv, UVIB and T-activin (the course also was
      begun after the second procedure of UVIB). The patients were observed for 9
      months. An advantage of the combination of phosphogliv, UVIB and referon,
      providing a stable remission in 36.3% of the patients for 9 months was
      demonstrated.

PMID- 14569881
TI  - [Toxicological cardiology].
AB  - The general cardiac signs and symptoms of acute drug poisoning and the treatment
      guidelines were presented in this article. The cardiovascular drugs toxicity and
      ethano-induced cardiac injury were discussed. The special interest was put on the
      drugs which cause QT prolongation and induce torsades de piontes (TdP).

PMID- 14569882
TI  - [Side effects, unwanted drug interactions and the problem of cardiotoxicity].
AB  - The problem of drug interactions is very important in pharmacotherapy. The
      interactions of some drugs (antihistamines, macrolides, fluoroquinolones,
      cisapride) with other can induce ventricular arrhythmias. A lot of non
      antiarrhytmic drugs can prolong the QT interval, induce torsade de pointes and
      cardiotoxicity.

PMID- 14569883
TI  - [Cardiotoxicity of vertebrates venoms].
AB  - Vertebrate species (fish, amphibians and reptiles) with cardiotoxic venoms
      properties are described in the paper. A regulatory problems related to breeding
      of venomous animals are also included.

PMID- 14569884
TI  - [Cobra bites].
AB  - The growing trend toward the collection of exotic snakes by private collectors
      increases the danger to health and life. The analysis of the cases which have
      occurred in USA, England, Germany and Poland shows that only quick and united
      effort of experts from the different fields and antivenoms can save the life.

PMID- 14569885
TI  - [Biological and toxic effects of ethanol: diagnostics and treatment of acute
      poisonings].
AB  - Ethyl alcohol (ethanol) is readily absorbed from all parts of the
      gastrointestinal tract due to its hydrophilic potential. The biological effects
      in humans refer to practically every organ and system. The basic enzyme involved
      in its oxidation is alcohol dehydrogenase. Another important metabolic pathway is
      the Microsomal Ethanol-Oxidizing System (MEOS). Toxic effect on basic cell
      functions is produced both by ethanol and acetic aldehyde, its oxidation product
      which accounts for most of the acute and delayed effects of ethanol toxicity. In
      acute ethanol intoxication's the CNS symptoms are the first to manifest. Ethanol
      affects the CNS functions mainly through stimulating opiate and benzodiazepine
      receptors and a number of neurotransmitters. However, the attempts to diminish
      the toxic effects of ethanol on CNS by blocking the affected receptors have
      proved to be ineffective. In acute poisoning a basic essential is to sustain
      vital functions by following the principles of intensive care. Each case of acute
      ethanol intoxication must be subject to neurological examination for possible
      cerebro-cranial traumas. The diagnostics and treatment procedures should take
      account of the possible symptoms: convulsions, respiratory and cardiac failure,
      hypoglycemia, hypothermia, and severe gastric dysfunction. Vital signs monitoring
      and control of acid-base and water-electrolyte balance are a must. The toxic
      properties of ethanol metabolites can be particularly hazardous to patients
      treated with disulfiram. The patients who develop "antabuse response" should be
      given immediately iron and vitamin C intravenously.

PMID- 14569886
TI  - [Acute poisoning with selected hepatotoxic agents: biochemistry of toxic effect,
      clinical symptoms and treatment].
AB  - The paper discusses etiopathogenesis, clinical symptoms and treatment in acute
      poisoning with hepatotoxic agents. The liver is a critical organ in acute
      poisoning with Amanita phalloides, carbon tetrachloride, iron compounds and
      isonicotinic acid hydrazide. Based on literature reports and own experience the
      authors present the current outlook on the specific treatment of acute poisoning
      with these xenobiotics. Special consideration was given to biochemical
      etiopathogenesis of hepatoxicity: oxidative stress, lipid peroxidation and
      impaired homeostasis of calcium ions and glutathione. Basic principles were also
      discussed of conservative treatment in hepatic encephalopathy due to toxic liver
      necrosis.

PMID- 14569887
TI  - [Paracetamol: therapeutic action, pathogenesis and treatment of acute poisonings
      complicated by severe liver damage].
AB  - The biosynthesis of prostaglandins proceeds in the presence of fatty acid
      cycloxygenases (COX-1, COX-2). COX-1 is responsible for the synthesis of
      prostaglandins indispensable for normal homeostasis, while COX-2 regulates local
      expression of pro-inflammatory prostaglandins. Paracetamol is a selective
      inhibitor of COX-2 thus having an analgesic and antipyretic potential. The drug
      is metabolised primarily in the liver. About 5% of the dose transforms into N
      acetylo-p-benzoquinoneimine (NAPQI), a highly active compound. Ingestion of a
      single paracetamol dose higher than 8 g leads to a depletion of hepatic
      glutathione reserves and a loss of the detoxifying property of the liver. As a
      result, hepatic necrosis develops. The specific antidote is N-acetylcysteine
      (NAC). If applied within 10-15 h since the poisoning it enables complete
      survival. The efficacy of specific treatment decreases after 24 h but blood
      paracetamol is an indication for NAC therapy. The surviving patients with
      advanced paracetamol poisoning require long-lasting conservative treatment with
      ornithine and phospholipids as well as a light diet.

PMID- 14569888
TI  - [Lipoproteins HDL and coronary artery disease: a molecular mechanism of fibrate].
AB  - The importance of dyslipidemia in the development of cardiovascular disease is
      now recognized as a central factor of equal, if not greater significance than any
      other risk factor. Although correction of high level of low-density lipoproteins
      (LDL) has been regarded now as the main goal of therapy, it has now been
      reaffirmed that the contribution of low level of high-density lipoproteins (HDL)
      to the risk of ischaemic heart disease should also be considered. In the therapy
      of dislipidemias with hipertriglyceridemia and decreased level of HDL lipoprotein
      fibrates play an especially important role. In the article the molecular
      mechanism of fibrates action is presented.

PMID- 14569889
TI  - Clinical and scintigraphic (99mTc-MIBI SPECT) heart evaluation in young acutely
      carbon monoxide poisoned patients.
AB  - The results of myocardial (99mTc-MIBI SPECT) perfusion scintigraphy according to
      clinical evaluation, ECG, biochemical factors of necrosis and indicators of
      carbon monoxide (CO) poisoning severity are described in the paper. Under
      examination there were 88 young (mean age 26 +/- 8.5) acutely CO poisoned
      patients without previous cardiac illness history, treated at the Department of
      Clinical Toxicology Jagiellonian University Medical College in Krakow in 1996 to
      2002. Measurement of COHb level, blood lactate concentration, duration of
      exposure and ECG examination were performed on admission. The enzymes activity
      ALT, AST, CK, MB-CK, was evaluated after 24-48 h. The severity of CO poisoning
      was estimated basing on age, duration of exposure, COHb level, blood lactate
      concentration and the patient neurological state on admission. 99mTc-MIBI SPECT
      was performed on days 1 to 5 post admission. The abnormalities in scintigraphic
      scans were assessed according to arbitrary accepted scale (0-IV). Conventional
      biomarkers creatine kinase, ALT and AST were insufficient for evaluation the
      heart injury in CO cutely poisoned patients. A statistically significant
      differences in the blood lactate concentration with regard to degree of
      scintigraphic changes have been observed. The ECG curves monitored from admission
      to discharge were analyzed in the study. Tachycardia was observed in all the
      patients but no statistically significant differences were found between the
      subgroups divided according to the degree of scintigraphic scans. Conductivity
      disturbances were detected mainly in patients qualified to higher then the first
      degree of scintigraphic changes. ECG signs of myocardial ischemia were the most
      frequent in patients with biggest pathological changes in 99mTc-MIBI scans. The
      changes in 99mTc-MIBI SPECT were observed in the majority of acutely CO poisoned
      patients. The mutual dependence of patient's condition based on neurological
      symptoms, carbon monoxide poisoning severity scoring and the degree of
      scintigraphy changes was found. The examination performed indicate that 99mTc
      MIBI SPECT scintigraphy can be method of choice for evaluation the heart injury
      in patients after acute CO intoxication.

PMID- 14569890
TI  - [Suicidal poisoning with antihypertensive drugs].
AB  - In the period from 1990 to 2002, 201 patients with suicidal antihypertensive
      drugs poisoning were treated, including 138 women and 63 men from 15 to 84 (mean
      36) years old. The main causes of suicides were various kinds of depression (63%)
      as well as psychopathy and/or sociopathy (16%) and schizophrenia (10%). Twenty
      eight patients attempted repeatedly to commit suicide. Thirty six persons were
      poisoned by only antihypertensive drugs, in 165 remaining cases intoxications
      were mixed including antihypertensive and other different medications. beta
      blockers (38.3%), calcium channel blockers (34.8%), angiotensin converting enzyme
      inhibitors (24.3%) and diuretics (2.5%) were used in suicidal attempts. There
      were no suicidal poisonings with angiotensin II AT1 receptor antagonists, alpha 1
      blockers and imidazole receptor agonists. In the examined group three patients
      died of cardiogenic shock, electromechanical dissociation and secondary acute
      respiratory failure resistant to therapy. The drugs used in these cases were
      propranolol, amlodipine, theophylline, captopril, doxepine, propafenone,
      furosemide, methimazole and alcohol. Mortality rate in antihypertensive drug
      poisonings was 1.5%.

PMID- 14569891
TI  - [Cardiotoxic agents in the practice of the toxicological laboratory].
AB  - Basing on toxicological examination performed between December 1, 2001 and
      November 6, 2002 the analysis of cardiotoxic agents was carried out. As much as
      69.7% of 2523 positive results was related to cardiotoxic agents. Ethanol (57.4%)
      followed by anticholinergic drugs (15.7%), amphetamine (11.6%) and carbon
      monoxide (8.9%) were most frequently determined cardiotoxic agents. Relatively
      small number of cardiovascular medication drugs (0.3%) was stated in biological
      samples. The cardiotoxic agents were detected mostly in men (68.8%), even after
      ethanol was excluded from the analysis (54.8%).

PMID- 14569892
TI  - [Amphetamine and derivatives related death in the aspect of forensic toxicology].
AB  - Amphetamine and derivatives are the crucial theme in the problems of forensic
      toxicology. The paper is based on the study of 20 cases of deaths in which
      amphetamine and/or derivatives were involved as the cause of death. Toxicological
      examinations of the autopsy specimens were performed with the use of HPLC/MS
      method in chemical positive ionization mode (APCI) after liquid--liquid
      extraction. The toxicological findings obtained in particular cases indicate that
      the majority of cases under consideration were complex. Among all 20 cases only
      two, probably suicidal deaths, were a result of amphetamine abuse. Some of them
      which were violent deaths (murder, gun-shot, hanging, drowning) of people under
      the influence of drugs. The majority of cases which were probably fatal accidents
      caused by the interaction of various mixtures of xenobiotics which included also
      opiates, cocaine, benzodiazepines besides amphetamine and derivatives. The
      concentrations of xenobiotics detected in these cases fit a relatively large
      range. One case is worth mentioning. This is a death of a permanent amphetamine
      user who survived two weeks with hematoma in brain in which amphetamine was
      detected postmortem. The report also discuss amphetamine and derivatives
      metabolic problems and contains useful data for medico-legal purposes.

PMID- 14569893
TI  - [Preliminary research on opioid mutagenicity].
AB  - The aim of the study was a preliminary recognition of genotoxic effect of
      methadone, using a culture of lymphocytes obtained from the blood of 23 opiate
      dependent patients from methadone maintenance treatment programme conducted at
      the Department of Clinical Toxicology of Jagiellonian University Medical College.
      The micronuclei (MN) occurrence and the number of sister chromatids exchange in
      methaphasal plate were the examined markers of mutagenesis. Two control groups
      differently exposed to environmental mutagenic factors were used to verification
      of results. The increased fraction of cells with the high number of sister
      chromatids exchange (HFC) indicate on possible genotoxic effect of methadone,
      however in the populations exposed also to other mutagenic factors the effect is
      not so evident.

PMID- 14569894
TI  - [Longevity of physicians and medical scientists born from 1880 to 1904].
AB  - Analysis of biographies of 319 physicians (302 men and 17 women) born from 1880
      to 1904, who died from natural causes, was carried out on the basis of annals of
      medical universities in Poland. Due to small number of women they were excluded
      from further analysis. There were no statistically significant differences in
      duration of life between medical scientists- professors, Ph.D. (n = 212, mean =
      73.9 +/- 10 yrs) and physicians with the doctor's degree or without any
      scientific degrees (n = 90, mean = 72.6 +/- 11.4) and among medical scientists
      working in different fields--basic research (n = 42, mean = 75.1 +/- 9.7), non
      invasive disciplines (n = 64, mean = 72.0 +/- 9.9), surgical disciplines (n = 89,
      mean = 74.4 +/- 11.0), disciplines with limited contact with patients (n = 17,
      mean = 75.8 +/- 9.0). Average life expectancy at the age of sixty in the whole
      examined group (16.1 +/- 8.6 yrs) was not statistically different from the
      general population of men born in the same period (15.1 yrs).

PMID- 14569895
TI  - [Is total cholesterol a good predictor of attempting suicide?].
AB  - The aim of the study was to verify a correlation between total cholesterol and a
      risk of attempting suicide. There has been data suggesting that individuals with
      low cholesterol are prone to commit a suicide. This could be due to the altered
      serotonin metabolism that in turn increases the level of aggressiveness,
      compulsiveness an promotes attempting suicide. We analyzed data from 300
      poisonings, also with drugs, which were considered as attempted suicides. There
      was no evident correlation between cholesterol level and incidence of poisoning
      with drugs, acute alcohol poisoning and chronic alcohol abuse. Moreover, we did
      not find a correlation between low cholesterol level and a need of psychiatric
      treatment, both in hospital and in outpatient clinic. Further study are needed to
      elucidate the exact role of low cholesterol as a predictor of suicide attempt.

PMID- 14569896
TI  - [Psychological analysis of family situation of youthful suicide].
AB  - The aim of the studies was analysis of youthful suicides family situation. The
      whole group of being studied was 294 suicides, of women end men, at 15-25 age.
      The studies was realized in the two centres, were the suicides was hospitalized:
      in the Lublin Regional Toxicological Centre, and at the Psychiatric Department of
      the Lublin Medical Academy, in the period from 2000 to 2002 year. The most
      numerous group was made of suicides at 15-19 age. There were 53% of men, and 47%
      of women. The most of them are bred in full family. Nearly the half of suicides'
      families was alcoholic families. 55% of being examined indicate the negative
      relationship between parents, 25% define them as very negative. More than the
      half of suicides estimate the homely atmosphere as negative; 25% evaluate them as
      very negative.

PMID- 14569897
TI  - [Severe mixed poisoning with diltiazem, potassium and magnesium: a case report].
AB  - We report the case of 52-year-old woman, who ingested 3.6 g of diltiazem, 16 g of
      potassium chloride and 6.5 g of magnesium, in a suicide attempt 4 hours before
      admission. She developed cardiorespiratory failure, with severe hypotonia and
      acute renal failure, in ECG third degree atrioventricular block was stated. The
      highest potassium concentration was 8.0 mmol/l, magnesium 2.15 mmol/l. As a
      result of multiple pharmacologic intervention, including intravenous fluids,
      calcium, glucagon, dopamine, dobutamine, norepinephrine, transvenous pacing and
      peritoneal dialysis (haemodynamic instability makes haemodialysis noneffective)
      the haemodynamic stabilization of cardiovascular system and normalization of
      potassium and magnesium concentration were achieved. The diltiazem concentration
      was measured using liquid chromatography, the result was 0.89 microgram/ml. She
      was discharged in a good clinical condition on day 26th.

PMID- 14569898
TI  - [Acute poisoning with nifedipine and acebutol: two cases].
AB  - In this paper the case of intoxication in two women (19-year-old and 23-year
      old), who in suicide attempts ingested at the same time different doses of
      nifedipine and acebutol. In 23-year-old woman 4 hours post ingestion
      cardiorespiratory arrest was stated. Resuscitation procedures were ineffective,
      she died. Acebutol concentration in postmortem blood was 24.1 mg/l and nifedipine
      1.8 mg/l. The second one (19-year-old) was treated successfully, only mild
      cardiac disturbances were observed. Acebutol concentration in blood was 1.8 mg/l,
      nifedipine was not stated.

PMID- 14569899
TI  - [Cardiotoxicity of amantadine in acute poisoning: a case report].
AB  - We report the case of an adolescent, 15-year-old woman, who ingested 4.0 g of
      amantadine in a suicide attempt 2 hours before admission. She developed central
      nervous system symptoms including confusion and psychomotor agitation. The main
      cardiovascular symptoms were due to disturbances in atrioventricular conduction
      and propagation of stimuli in sinus node. All cardiovascular symptoms
      disappearanced after 12 hours of admission, CNS symptoms were observed 48 hours.
      No other systems were involved. She was discharged in a good state on day 5th.

PMID- 14569900
TI  - [Severe felodipine and theophylline poisoning successfully treated by 4
      aminopyridine: a case report].
AB  - The case of a 51-year-old man who ingested 100 mg of felodipine (Plendil, 20
      tablets a 5 mg) and 9 g of theophylline (Theospirex retard, 30 tablets a 300 mg)
      is presented. The patient developed severe hypotension, tachycardia, circulatory
      insufficiency and paralytic ileus. No ECG effects were observed. Although
      felodipine led to a reduction in the bioability of theophylline, the serum
      theophylline concentration 15 h after the admission was 92 mg/L (the therapeutic
      concentration of theophylline 10-20 mg/L). The protracted hypotension did not
      respond to vasopressor and calcium therapy. The addition of 4-aminopyridine (4
      AP) infusion resulted in fast receding of poisoning symptoms: increase of blood
      pressure, receding of circulatory insufficiency and metabolic acidosis, and
      return of peristalsis. This case suggests the usefulness of 4-AP in the treatment
      of poisoning by dihydropyridine derivatives. However, confirmation of the
      effectiveness of this substance for pharmacotherapy of dihydrophyridine
      derivatives poisoning requires further clinical research. The influence of 4-AP
      on calcium channels is indirect. It blocks potassium channels K1 in cytoplasm
      side which makes potassium stay inside the cell leading to depolarisation and
      opening of voltage-dependent calcium channels.

PMID- 14569901
TI  - [Successful treatment by 4--aminopyridine of three cases of severe verapamil
      poisoning].
AB  - Three cases of verapamil intoxication were presented. In all cases shock and
      circulatory insufficiency were observed. In case no. 1 respiratory insufficiency
      and confusion were observed, in case no. 3 second-degree atrioventricular block
      was noted. The protracted hypotension (shock), circulatory insufficiency and
      atrioventricular block did not respond to calcium therapy, high dose of
      vasopressor amines and atropine. The addition of 4-aminopyridine (4-AP) infusion
      resulted in fast receding of poisoning symptoms; receding of atrioventricular
      block, cardiogenic shock and circulatory insufficiency. These cases suggest the
      usefulness of 4-AP in the treatment of verapamil poisoning. However, confirmation
      of the effectiveness of this substance for pharmacotherapy of calcium antagonists
      poisoning requires further clinical research. The influence of 4-AP on calcium
      channels is indirect. It blocks potassium channels K1 in cytoplasm side which
      makes potassium to stay inside the cell leading to depolarisation and opening of
      voltage-dependent calcium channels.

PMID- 14569902
TI  - [The use of intra-aortic balloon counterpulsation in the treatment of severe
      hemodynamic instability from myocardial depressant drug overdose].
AB  - A case of refractory hemodynamic instability following metoprolol and diltiazem
      overdose is reported. Management included intra-aortic balloon counterpulsation
      as an adjunct to pharmacologic therapy in cardiogenic shock from overdose of
      myocardial depressant drugs.

PMID- 14569903
TI  - [Cardiac drugs severe intoxications requiring artificial pacemakers].
AB  - In this study we present 11 cases of severe drug's intoxications connected with
      serious rhythm disorders, in which establishment an endocavital electrode and
      artificial pacemaking were saving-life interventions. Among them Ca-antagonists,
      digoxin, beta-blockers, angiotensin convertase inhibitors intoxications were
      observed. 9 cases were treated successfully, 2 patients died. In 2 cases we
      established electrode, but it wasn't useful. Previous conventional treatment of
      intoxicated patients with disorders of atrioventricular conductance and impulse
      creation requires complementation with more aggressive procedures of using
      artificial pacemaking in properly quick time.

PMID- 14569904
TI  - [ECG disturbances as a consequence of cardiac drugs overdose].
AB  - For many years ECG disturbances caused by cardiologic drugs are in the spot of
      our interests. In the Poisoning Centers patients who ingested large amounts of
      these drugs are treated so there are possibilities to investigate such kind of
      ECG changes. For the demonstration we present ECG-s illustrating disturbances in
      the course of intoxication with calcium channel blockers, beta antagonists and
      digoxin.

PMID- 14569905
TI  - [Analysis of cases of acute poisoning with cardiovascular drugs].
AB  - A retrospective analysis of cases of acute poisoning with cardiovascular drugs in
      the period from 1999 to 2002 has been carried out. A total of 72 poisoned
      patients was treated in the study period in the Lublin Regional Toxicological
      Centre. The poisoned were mostly women (69%), out of whom 76% were under 30. More
      than 66% were the cases of mixed poisoning, especially with antidepressant or
      sedative-hypnotic drugs. Alcohol poisoning was diagnosed in 28% of cases and it
      was statistically more frequent in men than in women (54.6% and 16.0%,
      respectively). Cardiovascular drugs were the most frequent cause of suicidal
      poisoning cases, i.e. beta-blockers were the cause of 40% poisoning cases, ACEI
      inhibitors--22%, and calcium channel blockers--19%. In 25 cases (in 18 women and
      7 men) severe poisoning caused bradyarrhythmia or hypotonia which resulted in the
      death of 2 patients.

PMID- 14569906
TI  - [Intoxication with tricyclic antidepressants in 2000: regional toxicological
      poison data from the center in Lublin].
AB  - The thirty eight tricyclic antidepressants (TCA) intoxicated patients were
      hospitalised during 2002 year in the Regional Toxicological Center in Lublin. The
      attempted suicides were the reason of administrating TCA drugs. All hospitalised
      patients did not suffer from cardio-vascular diseases. Analyzing the cases of
      patients intoxicated with TCA we took into account: heart rate, blood pressure,
      ECG record--QRS, QT, PQ, ST abnormalities, blood gases ((pH, pCO2, pO2,
      saturation), and serum drug concentration. The 50% of our TCA intoxicated
      patients demonstrated cardio-vascular symptoms confirming our expectations.

PMID- 14569907
TI  - [Acute poisoning with cardiovascular drugs: data from Acute Poisoning Ward in
      Tarnow].
AB  - In this paper an analysis of poisonings with cardiovascular drugs treated in the
      II Ward of Internal Diseases and Acute Poisonings in Tarnow, in the years from
      1996 to 2001, is presented. In 6 years 66 patients were treated (4.5% of all
      treated toxicological cases). The most frequent kind of drugs were
      antihypertensive drugs (44 cases), mainly beta-blockers--17 cases. No fatalities
      were observed. Suicidal poisoning with propafenone in 22-year-old man is
      presented.

PMID- 14569908
TI  - [Two cases of rhabdomyolysis with a different clinical course].
AB  - Rhabdomyolysis is a syndrome provoked by the injury to skeletal muscles and the
      release of muscle cell contents into the plasma. The aetiology and clinical
      course are extremely variable. This is sometimes the reason of the diagnostic
      difficulties or even errors. Acute renal failure is the often and serious
      complication of rhabdomyolysis. The correct and early diagnosis of rhabdomyolysis
      is a key to successful treatment and prevention of the possible complications.
      Two cases of rhabdomyolysis with different aetiology and clinical course are
      presented in this paper. A 39-year-old man was admitted with the symptoms of
      dyspepsia. During the first day he developed the acute renal failure and later
      the acute respiratory failure. The initial serum creatine phosphokinase (CPK)
      activity was about 225,000 U/L. Haemodialysis, plasmapheresis and respiratory
      therapy were performed. A 25-year-old man was admitted with the swollen leg of
      the uncertain origin. His initial CPK activity was 18,993 U/L. The patient was
      treated with the infusions of fluids and sodium bicarbonate. He did not develop
      renal failure. Despite of the initial diagnostic doubts, in both cases the
      outcome was excellent.

PMID- 14569909
TI  - [Neuroleptic malignant syndrome].
AB  - Neuroleptic malignant syndrome (NMS) is the most dangerous side effect of
      phenothiazines therapy. In the period of time from 1995 to 2002 in the Intensive
      Toxicological Unit there were five patients, 3 men and 2 women, aged from 25 to
      62 (average 44.2) years-old, admitted from the regional inpatients psychiatric
      units with the diagnosis of pneumonia and/or sepsis. The patients about 48-72
      hours before admittance were given some phenotiazine derivatives (promazine,
      perphenazine, clozapine, pipamperon) and/or buthyrophenone (haloperidol) because
      of psychotic state. Altered consciousness, muscle rigidity, hyperpyrexia (39.0
      41.0 degrees C), sweating, tachycardia (120-150/min.), tachypnoea (respiratory
      rate more than 25/min.) and high level of creatine kinase activity (23,751
      112,288 U/l) dominated. Only one patient had clinical picture of pneumonia.
      Because of the rapid development of acute respiratory failure,
      respirathorotherapy was initiated and continued for 8 and 10 days in two patients
      respectively. Transient thrombocytopenia (26,000/microliter) in one subject was
      observed. The neuroleptic drug was withdrawn and intensive supportive care with
      administration of bromocriptine (15-20 mg/24 h) was provided. None one of the
      doctors told the patients about the possibility of NMS during phenothiazines
      therapy.

PMID- 14569910
TI  - [Suicidal salicylate intoxications and unintentional percutaneous poisoning with
      salicylic ointment].
AB  - Suicidal salicylate poisonings are presented in 49 patients, 33 women and 16 men,
      aged from 18 to 71 (mean 37) years. Mixed poisonings with multiple agents were
      four times more frequent, had more severe clinical course and demanded longer
      hospitalisation than acute intoxications with salicylates alone. Four patient
      were over 65 years old (8.2%). Difficult economic situation of geriatric
      population in Poland had no effect on frequency of suicidal attempts in the
      studied cohort. There were no fatalities in the studied group. There were two
      unintentional systemic poisonings due to topical administration of the 10%
      salicylic acid ointment for wide spread skin lesions (more than 80% of body
      surface) in two patients with exudative psoriasis.

PMID- 14569911
TI  - [Non-invasive positive pressure respiration in acute respiratory failure caused
      by suicidal oral intoxication with morphine sulphate].
AB  - In this article we described a 15-year-old female who was admitted to the Clinic
      of Toxicology because of suicidal, oral intoxication with morphine sulphate in
      the total dosage of 360 mg. In the Clinic the patient was in I degree degree of
      Matthew coma scale, with the heart rate about 90/min., blood pressure 105-100/70
      60 mmHg, breath rate about 7/min. The arterial blood gas analysis showed acute
      respiratory failure (pCO2 64.1 mmHg, pO2 54.9 mmHg and SO2 88%) in spite of
      constant and intravenous Naloxone infusion. The mother of the patient, who was a
      nurse, had not agreed to endotracheal intubation and invasive method of
      respiration. Because of that reason the non invasive positive pressure
      ventilation with the BiPAP Synchrony apparatus were used with IPAP 14 cm H2O,
      EPAP 5 cm H2O, breath rate 12/min, time of inspiration 2.0 sek., time of
      inspiration grow 600 msek. After 15 minutes of respiration pCO2 decreased up to
      40 mmHg, pO2 increased up to 73.3 mmHg and the oxygen saturation of arterial
      blood was 95.7-98.6%. Respiratory failure was observed every time when apparatus
      was withdrawn. After 24 hours of ventilation by BiPAP Synchrony apparatus the
      full stabilization of respiratory tract was achieved.

PMID- 14569912
TI  - [Consciousness disturbances: a case report of Munchausen by proxy syndrome in an
      elderly patient].
AB  - In this article an 80-year old female who was admitted to our hospital because of
      syncope. After effective therapy the decision about discharging of the patient
      was taken. This information was met with firm refusal of the patient's
      granddaughter. From this time the state of health of the elderly patient was
      getting worse after each granddaughter's visit. The consciousness disturbances
      from somnolence to coma appeared. The clinical symptoms increased in the
      afternoon and in the evening decreased late at night and in the morning. In some
      toxicological tests there was very high serum benzodiazepines level (160.7
      ng/ml). The inspection of the doctor's permanent and temporary orders excluded
      the possibility of administering the benzodiazepines by the hospital's staff.
      After the honest talk with the granddaughter and reducing her contacts with the
      patient, the serum benzodiazepines started to decrease to the zero level and the
      consciousness disturbances disappeared.

PMID- 14569913
TI  - Acute poisoning with Tricholoma equestre of five-year old child.
AB  - This report presents the first case in pediatric literature of the acute
      intoxication of a five-year old male child who ate 300-400 grams of Tricholoma
      equestre daily for four consecutive days before the onset of poisoning. The
      symptoms included acute respiratory failure with the need of respiratorotherapy,
      muscle weakness concerning especially the pelvic girdle and the urinary bladder.
      The boy could not sit or stand up without help and the bladder had to be
      catheterised, several times daily, to avoid urine retention. The biochemical
      tests showed only minor muscle injury with maximal activity of creatine kinase
      306 U/L, aspartate aminotransferase 39 U/L, alanine aminotransferase 56 U/L. No
      other causes responsible for the signs mentioned above such as trauma, viral,
      bacterial, neurologic and immune diseases or exposure to medications were found.
      All the symptoms and biochemical abnormalities disappeared within 12 days of
      hospitalisation. We believe that the clinical picture of poisoning with this wild
      mushroom might be different in children and adults.

PMID- 14569914
TI  - [Vaccine, methadone and zebrafish].
AB  - Substances of abuse have been known since antiquity till now. Current trends in
      neurobiological and genetical study related to drug dependency were presented in
      the study. The trial of preparation a cocaine vaccine and the new hope for
      dependent people coming from investigation of Zebrafish were also described.

PMID- 14569915
TI  - Anal dilatation: 'use and miss-use'.

PMID- 14569916
TI  - [Conservative surgery for distal rectal tumors: illusion or reality?].

PMID- 14569917
TI  - [Videolaparoscopic adrenalectomy in Conn syndrome. Analysis of 39 case
      observations].
AB  - The authors retrospectively analyse 39 patients affected by Conn's syndrome,
      which have been observed since 1985, and discuss the results of surgical approach
      using the new technologies. In particular, the introduction of laparoscopy,
      technique that has been applied almost exclusively since the last seven years,
      has revealed being the "gold standard" for the surgical treatment of this
      disease. The adrenal underlying lesions are indeed almost always monolateral,
      small in size and present very rarely malignancy in their biological behaviour.
      Furthermore, the authors, although lacking of personal experience, propose the
      possibility of a more conservative treatment of the adrenal lesions with a simple
      "enucleation", whose feasibility also in laparoscopy has recently been shown by
      some authors. Anyway, the Authors believe that this technique of a partial
      adrenalectomy could be chosen in selective cases of bilateral adenomas or
      hyperplasia or in those lesions which are placed in an easily accessible
      peripheral site.

PMID- 14569918
TI  - [Biliary complications of laparoscopic cholecystectomy: our experience compared
      with laparotomic cholecystectomy].
AB  - Major bile ducts injuries during cholecystectomy were one of the most common
      complications, but they were becoming rare. With the introduction and the fast
      diffusion of laparoscopy their incidence has increased. For this reason we have
      reviewed our experience about open and laparoscopic cholecystectomy. We report 18
      patients, 8 male and 10 female with age ranged from 27 to 73 years, with common
      bile duct injuries. Only three patients (20%) underwent surgery in our Department
      of Surgery of the University of Cagliari. Of these patients, two were operated on
      open and one laparoscopic cholecystectomy. They represent 0.08% and 0.36% of the
      respective groups. The most common cause of this complication is peritonitis
      (94.5%), followed by bleeding and congenital anomalies of the biliary tree, that
      were present in 5.5% respectively. The conversion to laparotomy was necessary in
      3.9% of our patients, while residual choledocholithiasis in one patient was
      treated by laparotomic reexploration because of the unsuccessful ERCP. In summary
      in our opinion the prevention of this complication depends on appropriate
      indication and choice of the patients, as well as an adequate training. The ERCP,
      if indicated, must be done before laparoscopic cholecystectomy.

PMID- 14569920
TI  - [Glomus tumor and neovascular syndrome of the arm: a clinical case].
AB  - Glomus tumour represents a benign tumor which originates from myoepithelial cells
      of arteriovenous anastomosis that has a preference for subungual localization
      with painful and multiform symptomatology. A fifty-year-old female presented a
      vasospastic symptom with hyperalgesia and cold hypersensitivity in the fourth
      finger of the right hand. There was a little palpable tumefaction and after an
      echography, we decided for surgical revision. Differential diagnosis with
      Raynaud's phenomenon is very important but not simple. The diagnosis is often
      late. MRI and angio-MR with its typical symptomatology could give the accurate
      diagnosis. The therapy is only surgical. The excision must be very careful making
      sure to spare the nervous structures.

PMID- 14569919
TI  - [Clinical study of aortic co-involvement in lumbo-aortic lymph node metastasis of
      testicular carcinoma].
AB  - The Authors review the international literature about the frequency of vascular
      involvement (inferior vena cava and aorta) in the lymph node lumbo-aortic
      metastases of the testicular neoplasm. They report a case of a patient with an
      aortic involvement from lymph node metastases of a mixed (seminoma and germ cell)
      cancer of the left testis. They performed en bloc resection of the bulky
      metastases including the aorta involved. The literature data as well as the
      outcome of the operated case show a moderate survival also in patients with
      advanced disease.

PMID- 14569921
TI  - [Mechanical intestinal occlusion due to phytobezoars].
AB  - The Authors reporting two cases with ileus by phytobezoar in distal jejunum and
      ileum, respectively, and discuss the pathophysiologic mechanism responsible for
      the formation of bezoars. They expose the etiological and clinical factors of
      this uncommon cause of small bowel obstruction and also discuss the surgical
      technique that consists in the removal of the phytobezoar through enterotomy.

PMID- 14569922
TI  - Communicating oesophageal duplication: a case report.
AB  - Duplications of the oesophagus are rare congenital abnormalities and rarely
      communicate with the oesophageal lumen. They are commonly associated with other
      congenital malformations, such as spinal deformities, congenital heart disease,
      vertebral anomalies, malrotation of the bowel, Meckel's diverticulum. During a
      percutaneous endoscopic gastrostomy, performed because of a neurological
      dysphagia, the endoscopy revealed a very rare case of a 26-year old man affected
      by Klippel-Trenaunay syndrome, with an asymptomatic oesophageal duplication that
      communicated proximally and distally.

PMID- 14569923
TI  - Pyoderma gangrenosum of the "sinus mammarum" in ulcerative colitis.
AB  - The first part of this article deals with the report of a patient suffering from
      pyoderma gangrenosum of the "sinus mammarum" associated with asymptomatic
      ulcerative colitis. This is followed by a revision of the present
      epidemiological, etiological, pathogenetic and clinical knowledges about this
      systemic manifestation of chronic phlogosis of the colon. The Authors have
      analysed the treatment for this condition and emphasized the resistance of the
      cutaneous ulcer encountered to conventional medical therapy of the underlying
      colonic disease which proved to be efficacious only on the latter; this led to
      integrate traditional treatment with the use of perilesional injections of small
      doses of calcic heparin as an alternative to immunosuppressive drugs or surgery.
      Topical antithrombotic treatment, which can be justified by the histological
      findings of phenomena of the vasculitis in the edge of pyoderma gangrenosum,
      demonstrated to be crucial and represents a peculiarity in the case here
      reported, which is unique in the literature as far as the Authors know, since it
      has not been experimented by anyone else.

PMID- 14569924
TI  - [Role of thymectomy in the treatment of myasthenia gravis: considerations and
      personal cases].
AB  - The therapeutic impact of thymectomy on the clinical course of myasthenia gravis
      is still very controversial. In fact, while nowadays the surgical approach is
      widely adopted for thymomas, its role is still debatable in patients suffering
      from myasthenia gravis. The surgical approach of choice for total thymectomy is
      represented by median sternotomy. Other surgical methodologies include cervical
      access and partial sternotomy. All these approaches have shown excellent results
      in the exeresis of the thymus. More recently video-assisted thoracoscopic
      thymectomy has been proposed as a less invasive and similarly effective technique
      for the removal of this organ and the treatment of myasthenia gravis. Aim of the
      present study is to report Author's experience with thymectomy, emphasizing the
      data available in the international literature on the surgical mortality,
      complications and aesthetical results of the different surgical accesses.

PMID- 14569925
TI  - [Our experience with treatment of varicocele in a day-surgery protocol].
AB  - In the last few years the increasing interest for non-invasive operating
      techniques has allowed to reevaluate the sublinguinal varicocelectomy surgical
      technique for idiopathic varicocele surgical treatment. During the years 1998
      2001, 29 patients have been operated on sub-inguinal varicocelectomy (14 patients
      were suffering from idiopathic varicocele of third grade, 11 of second grade, 3
      of first grade, and 1 subclinical). Out of the 29 patients, only 10 were unable
      to procreate. All patients were operated under local anesthesia and discharged
      the same day (day-surgery). Owing to Authors' experience, the sublinguinal
      varicocelectomy by optical magnifying devices represents the "gold standard" in
      the idiopathic varicocele treatment because it allows to minimize relapsing
      rates, to limit post-operation complications, to improve the reproductive faculty
      of seminal fluid both qualitatively and quantitatively, to cut patient's
      operating costs significantly, to keep the operation time within acceptable
      limits, and to be easily learned and carried out.

PMID- 14569926
TI  - [Diagnosis and therapy of severe acute colitis, still an open issue. Our
      experience].
AB  - From a review of a series of 12 cases of whom 52 operated and of the literature,
      the Authors discuss about aetiology, pathogenesis and diagnosis of severe
      colitis. Clinical and laboratory findings, CT and plain films of the abdomen and
      at last colonoscopy should be evaluated very carefully for certainty diagnosis of
      a severe acute colitis or toxic megacolon. They suggest a multidisciplinary
      approach as fundamental for medical management, for indications and correct
      timing of surgical procedures and to decrease postoperative morbility and
      mortality. Total colectomy with ileostomy is recommended in emergency surgical
      treatment of this colonic acute diseases, whereas for urgency operation,
      performed not later than 48-72 hour of adequate medical treatment, colectomy is
      suggested with ileorectal or ileoanal anastomosis and ileostomy.

PMID- 14569927
TI  - [Tobacco and malignant tumors].

PMID- 14569928
TI  - [Cognitive function in oncologic patients: role of hormonal factors].

PMID- 14569929
TI  - [Contribution to the history of oncologic statistics in Russia (50 years of
      national and obligatory registration of cancer patients].

PMID- 14569930
TI  - [Development of a population-based system of cancer registries in Russia].

PMID- 14569931
TI  - [Possibilities and prospects of the development of an automated cancer registry
      network system].

PMID- 14569932
TI  - [Results of a prospective randomized investigation [Russia (St.Petersburg)/WHO]
      to evaluate the significance of self-examination for the early detection of
      breast cancer].
AB  - Indications for puncture or excision biopsy were significantly higher in the
      study group (7.5%) as compared with control (3.5%) (p < 0.01) in a randomized
      prospective controlled trial of a comprehensive breast cancer screening (123,748)
      carried out in the framework of a self-examination education program. In the self
      examination group, detection rates were higher both for benign (1.1%) and
      malignant (0.85%) tumors than in control (0.5% and 0.69%, respectively) (p <
      0.05). Early stage (T1NOMO, Tis) distribution difference in the study group and
      controls was insignificant--23 and 17.6%, respectively. Compliance with the
      program requirements including monthly or bimonthly self-examination was followed
      by higher 15-year survival rates (53.2%) in 70-75% as compared with
      controls(45.8%) (p = 0.05105): yet it did not affect mortality.

PMID- 14569933
TI  - [Correlation of involved lymph nodes in stomach cancer with immunologic
      characteristics of the host and of the tumor].
AB  - Correlations between certain factors and regional lymph nodes involvement with
      disseminated gastric cancer were investigated in 708 patients after stomach
      resection with lymph node dissection, without chemotherapy. Immune response of
      such nodes, their function and tumor localization in the stomach appeared to
      influence metastatic involvement most.

PMID- 14569934
TI  - [Incidence of post-Chernobyl leukemia and thyroid cancer in children and
      adolescents in the Briansk region: evaluation of radiation risks].
AB  - Leukemia (51: 1988-1998) and thyroid cancer (106: 1991-1998) incidence in
      children and adolescents after Chemobyl accident in Bryansk region was assessed.
      A significant increase over spontaneous incidence in the same category of
      population and during the same period was reported. Standardized thyroid cancer
      incidence for the region is 5.37 times the federal level (95% confidence
      intervals--4.40 and 6.49, respectively); the upward trend is significant. The
      same trend is characteristic of leukemia incidence/exposure dose correlation but
      is not significant. Standardized leukemia incidence is 1.04 times the federal
      level (95% confidence intervals--0.78% and 1.34, respectively), and tallies with
      the federal level, within the margin of error. The findings are clearly
      indicative of exposure to radiation being a factor of higher thyroid cancer
      incidence in children and adolescents in Bryansk region.

PMID- 14569935
TI  - [Oncologic risk factors in papillomavirus infection].
AB  - Cytological screening is essential for adequate diagnosis of gynecological
      cancer. Moreover, every effort should be made to identify such risks of cancer as
      viruses (HPV, Herpes simplex, cytomegalovirus, Epstein-Barr virus, etc.). When
      high risk HPV-16 and HPV-18 are detected, diagnostic strategies should include
      assay of blood prolactin and prolactin/TTH ratio. Virus-related tumors and
      various risk groups may be studied using HPV genotyping detection of high-risk
      alleles of certain genes. Hence, some HPV gene variants and gene polymorphism can
      be investigated as potential risk factors in women.

PMID- 14569936
TI  - [Effect of extensiveness of testicular germinoma on the choice of a treatment
      regimen].
AB  - Complex examination and treatment were given to 282 patients with testicular germ
      cell cancer. Diagnosis was histologically verified in all cases. Metastases at
      different sites were identified in 136 (48.2%). Seminoma was treated with
      telegamma radiation from the ROCUS-M installation; cases of non-seminoma
      pathology received VAB-6 and BEP regimes. Germ cell cancer staging was
      facilitated by joint use of up-to-date diagnostic procedures. X-ray examination
      of organs of the chest was performed in all cases and sometimes supplemented with
      CT. Ultrasound, CT and MRI were chiefly used for diagnosis of pathologies of the
      abdominal cavity and retroperitoneal space. Prognosis and chemotherapy regimes
      were based on tumor stage assessment. After therapy, recurrence-free cases and
      those with total regression were released from hospital. Oncological follow-up
      included tumor marker monitoring and dynamic X-ray examination of the chest,
      abdominal cavity and retroperitioneal space. When metastasis regression was not
      complete, surgery was indicated, if technically feasible.

PMID- 14569937
TI  - [Clinical trial of the monoclonal antibody drug mabthera (Rituximab) in the
      treatment of non-Hodgkin lymphoma].
AB  - Mabthera has been tested for its influence on relapsing and refractory low-grade
      non-Hodgkin's lymphoma in a comparative study using monotherapy (R) or in
      conjunction with CHOP (R-CHOP) chemotherapy. Out of 33 in-patients, effect was
      evaluated in 31 (rituximab monotherapy--16, R-CHOP--31). MabThera
      monochemotherapy proved effective in 62% of those who had received several other
      regimes, R-CHOP-74%. Both regimens were followed by long (ca.12 months) stable
      remissions. No difference in complete and partial remission duration was
      reported, whereas complete remission ranged 6-13 months, partial--2-24 months.
      Clinically significant results were 87.5% in the monotherapy group, and 87%--R
      CHOP. No correlation was found between the efficacy of both regimens, on the one
      hand, and morphological patterns of lymphoma, on the other. CHOP chemotherapy had
      been given to 7 out of 15 patients treated with R-CHOP. Four of them had partial
      remission thus suggesting a modulating effect of rituximab on the resistance of
      previous treatment. R-CHOP was well tolerated by all patients, irrespective of
      age, did not contribute to untoward side-effects and assured longer remission.

PMID- 14569938
TI  - [Anticytosine therapy for primary myelodysplastic syndrome].
AB  - A pilot study of anticytocine therapy (PCD) was carried out in 9 patients with
      primary myelodysplastic syndrome (MDS). After 12 weeks, 2 patients (22%) showed
      hematological response cutting down the need for washed-out erythrocyte
      transfusions by half or more. MDS progression at different stages was reported in
      4; transformation to acute myeloleukemia--2. PCD treatment is indicated in MDS
      patients, aged over 65, with a less than 10% blast level of the bone marrow, and
      without any risks of tumor progression.

PMID- 14569940
TI  - [Role of innate macrophages in DNA and protein biosynthesis in cultured cells of
      murine (line A) ascitic hepatoma].
AB  - Joint effect of high-density lipoproteins (HDLP) and glucocorticoids presence is
      responsible for increased protein and DNA biosynthesis in the cells of the
      hepatic parenchyme. Hepatic innate macrophages devour HDLP and glucocorticoids
      and release the A-1 tetrahydrocorisol-apolipoprotein complex which in turn is
      channeled into interstitial spaces to be captured by hepatocytes, thus
      stimulating protein and DNA biosynthesis. This mechanism was observed in cultured
      cells of murine ascitic hepatoma; it was regulated by macrophages present in
      incubation medium. The rate of protein and DNA biosynthesis remained constant
      unless HDLP and glucocorticoids were present in the medium and in a macrophage
      containing culture alone.

PMID- 14569939
TI  - [Tumor-associated hetero-organic antigens as markers of deranged cell
      differentiation and malignancy].
AB  - We used rat liver tissue slices and isolated hepatocytes to demonstrate that
      single exposures to a "weak" carcinogen 4-dimethylaminoazobenzol (DAB) or to a
      "strong" one, such as N-diethylnitrosamine (DENA), cause identical antigenic
      restructuring to occur. It presented as formation of membranous heteroorganic
      antigens of renal origin on hepatocyte surfaces. Antigens were associated with
      Zajdela's hepatoma; their synthesis lasted longer after exposure to DENA. They,
      however, were not identified in intact rat liver. Their synthesis, following
      single exposure, was assayed immunocytofluorimetrically. It is suggested that the
      antigens be used as markers of cell dysdifferentiation and malignancy and testing
      substances for carcinogenicity.

PMID- 14569941
TI  - [N-nitrosodiethylamine-induced changes in the liver of syrian hamster with
      superinvasive opistorchiasis].
AB  - Trematoda O. felinius-induced hepatic lesions were investigated in Syrian golden
      hamsters with superinvasive opistorchiasis. One hundred hamsters were divided
      into 4 groups: (1)--control; (2) N-nitrosodiethylamine (DENA), i.p., twice a
      week, 3 weeks, total dose 72 mg/kg; (3) metacercariae O. felinius, with drinking
      water, 3 injections per day, once in 2 weeks, and (4) metacercariae O. felinius,
      as in group 3, followed by DENA, as in group 2. Animals were sacrificed 12 months
      after the beginning of the study. No changes in the liver were found in group 2.
      Reddish protrusions, up to 4 cm in diameter, appeared on liver surfaces in groups
      3 and 4. Group 4 featured the highest relative and absolute weights of liver as
      well as clusters of oval cells and cholangiocellular tubules and
      cholangiofibrosis (in group 3, they were less visible). Electron microscopic
      examination identified hepatocytes with destructive changes to plasmalemma,
      nucleus and cytoplasmic organelles. Also, perisinusoidal cells (Ito cells)
      occurred. Tumor-bearing animals showed low hepatic cytochrome P-450. It is
      suggested that proliferative growth in the liver was stimulated by opistorchis
      invasion.

PMID- 14569942
TI  - [Immunotherapy of lung tumors in Balb/c mice].
AB  - Tissue-specific immune reactions were used to develop a method of dealing with
      malignant tumors. Injection of proteins isolated from lung tissue of mice
      (CBAxC57BL/6)F1, of varying age, into mice Balb/c with urethane-induced lung
      tumors cut the number of such tumors by half. Direct correlation was found
      between the magnitude and nature of effect and level of lung protein injection.

PMID- 14569943
TI  - [Percutaneous needle biopsy in the diagnosis of pancreatic cancer].
AB  - The data on two procedures of ultrasound-guided fine-needle biopsy of pancreatic
      masses in 81 patients are presented (1999-2001): for cutting biopsy--64, and
      aspiration--and 17. Pancreatic cancer was identified in 41, non-epithelial tumor-
      3, metastasis to pancreas--2 and indurative pancreatitis--21. Complication were
      rare: hematoma formation after interstitial biopsy--1 (1.6%) and subcutaneous
      seeding--1 (5.9%) after aspiration biopsy. Sensitivity, specificity and accuracy
      for cutting biopsy were 96.7, 100 and 96.9%, respectively: aspiration--90.9, 90.9
      and 88.3%, respectively. Ultrasound-guided transabdominal fine-needle biopsy of
      pancreas is a low-invasive and effective method of diagnostic verification. The
      cutting procedure was more effective than aspiration biopsy: also, it helped
      identify histological pattern of tumor and grade of malignancy. Patients with
      chronic indurative pancreatitis are to be followed up even when primary fine
      needle biopsy results are negative.

PMID- 14569944
TI  - [Long-term results of combined therapy for malignant ovarian tumors in girls].
AB  - A retrospective analysis was carried out of the data on 31 patients, aged up to
      15 years, suffering from germ cell ovarian tumors and treated at the Institute's
      Clinic (1980-1999). Overall 10-year and recurrence-free survival was 75.4% and
      52.2%, respectively. Conservative surgery proved the most effective component of
      combined treatment. Preference in choosing polychemotherapy modality should be
      given to platinum-based drugs.

PMID- 14569945
TI  - [Risk factors for the development of malignant neoplasms of the reproductive
      organs in women].

PMID- 14569946
TI  - [Long-term results of polychemotherapy for Hodgkin's disease in children].
AB  - In 1974-2000, 49 patients (up to 15 years), with Hodgkin's disease at different
      stages, for different reasons, received polychemotherapy alone. Overall 5-year
      survival was 72.4%; 10 years-64.5%, and 15 years--52.7%. A correlation was
      established between survival, on the one hand, and stage and general symptoms, on
      the other: stages--I-IIIA--76.8%; IIIB-IVAB--37.7%; polychemotherapy--6 cycles-
      67.9%; more than 6 cycles--100%; age up to 10 years--75.8%; more than 10 years-
      45%.

PMID- 14569947
TI  - [Novel pharmacologic form of ondansetron (Zofran)--lingual tablets in the
      prevention of cytostatic chemotherapy-induced loss of appetite, nausea and
      vomiting].
AB  - Ondanserton (zofran), 16-32 mg/24 hr, lingual tablets, 2 days, was administered
      in 40 patients with advanced tumors who received combination chemotherapy (ABVD)
      (9 patients with Hodgkin's disease), CHOP (16--non-Hodgkin's lymphoma), gemzar +
      cisplatin (6--ovarian and 5--breast cancer), CAF, AC and taxol + carboplatin)
      (4). Distinct prophylactic antiemetic effect, delayed effect (94%) included, was
      reported in the CHOP group: full control--64% and partial control in gemzar +
      cisplatin treatment (27%). Loss of appetite was prevented in most patients
      receiving CHOP and gemzar + cisplatin. Untoward side-effects of ondansetron were
      not registered.

PMID- 14569949
TI  - NME digest.

PMID- 14569948
TI  - [Multiple colorectal cancer].

PMID- 14569950
TI  - Licensing line.

PMID- 14569952
TI  - NME digest.

PMID- 14569951
TI  - [Favorable effect of sildenafil on erectile dysfunction in patients after
      radiotherapy for prostate cancer; randomised, double-blind, placebo-controlled
      crossover study].
AB  - OBJECTIVE: To determine the efficacy of sildenafil in patients with erectile
      dysfunction after external beam radiotherapy for prostate cancer. DESIGN:
      Randomised, double-blind, placebo-controlled, crossover study. METHOD: A total of
      406 patients with erectile dysfunction reported in their medical records who had
      completed external beam radiotherapy at least 6 months prior to the study, were
      approached by letter. Sixty patients were included in a study which lasted 12
      weeks. They received 50 mg of sildenafil citrate or placebo for two weeks; during
      week 2 the dose could be increased to 100 mg in the case of unsatisfactory
      erectile response. At week 6 patients crossed over to the alternative treatment.
      Data were collected using the validated 'International index of erectile
      function' (IIEF) questionnaire, and side-effects were recorded. Patients were
      given the possibility of continuing to a 6-week open-label phase. RESULTS: The
      mean age of those participating was 68 years. All patients completed the double
      blind phase. For the majority f questions in the IIEF questionnaire, there was a
      significant increase in mean scores from baseline with sildenafil, but of the
      patients with sildenafil, versus 18% with placebo. Ninety percent of the patients
      required a dose adjustment to 100 mg sildenafil, and 100% of the patients in the
      placebo group increased the dose. Side-effects were mild or moderate. Patients
      who proceeded to the open-label phase reported the same results as in the double
      blind phase. CONCLUSION: Sildenafil improved erectile function in about half of
      the patients with erectile dysfunction after external beam radiotherapy for
      prostate cancer, and it was well tolerated.

PMID- 14569953
TI  - Licensing line.

PMID- 14569954
TI  - NME digest.

PMID- 14569955
TI  - NME digest.

PMID- 14569956
TI  - Licensing line.

PMID- 14569957
TI  - PAT Program report: background and current status.

PMID- 14569958
TI  - ELPAT Program report: background and current status.

PMID- 14569959
TI  - Asbestos exposure from gasket removal.

PMID- 14569960
TI  - Stationary versus personal air sampling.

PMID- 14569961
TI  - Dynamic complexity of visuo-motor coordination: an extension of Bernstein's
      conception of the degrees-of-freedom problem.
AB  - Extending Bernstein's spatial conception of the degrees-of-freedom problem in the
      human motor system, we introduce a method developed from the theory of non-linear
      dynamics that allows one to quantify the spatio-temporal, i.e. dynamic,
      complexity of visuo-motor coordination. The correlation dimension D is used to
      measure the effective number of dynamic degrees of freedom in the coordination
      that a subject uses when performing a visuo-motor tracking task. The validity of
      the estimator employed is demonstrated. Visuo-motor coordination had a low
      dimensional (mean D-SD=6.07 -0.82) dynamic structure, which was consistent with
      deterministic chaos rather than with pure stochastic noise. D correlated with
      tracking performance, P. Both D and P were closely related to the degree of visuo
      motor compatibility that the task presented to the subject. However, for short
      periods of training P increased, but D did not. As these seemingly contradictory
      results suggest, our dynamic conception of the degrees-of-freedom problem may
      reveal far more intricate visuo-motor interactions than Bernstein could identify
      on the basis of his spatial analyses of bodily movement patterns and by the
      methods of evaluation that were available to him at the time.

PMID- 14569962
TI  - More on measuring fungal contamination inside walls.

PMID- 14569964
TI  - NME digest.

PMID- 14569963
TI  - NME digest.

PMID- 14569965
TI  - NME digest.

PMID- 14569967
TI  - NME digest.

PMID- 14569966
TI  - Interventions for metabolic and endocrine complications of human immunodeficiency
      virus/acquired immune deficiency syndrome and illicit drug use. Proceedings of a
      workshop. 26-27 November 2001.

PMID- 14569968
TI  - Licensing line.

PMID- 14569969
TI  - NME digest.

PMID- 14569970
TI  - Should allografts be used for routine anterior cruciate ligament reconstructions?
      Yes, allografts should be used in routine ACL reconstruction.

PMID- 14569971
TI  - Should allografts be used for routine anterior cruciate ligament reconstructions?
      No, allografts should not be used for routine ACL reconstruction.

PMID- 14569972
TI  - [What is your opinion concerning recurrent aphthous stomatitis?].

PMID- 14569973
TI  - [Define the concept of loudness recruitment. How is this finding to be evaluated,
      in which lesions is it to be demonstrated and what effects has this phenomenon on
      the hearing?].

PMID- 14569974
TI  - [Surgical techniques of microvascular surgery].

PMID- 14569975
TI  - Detection of thyroid carcinoma.

PMID- 14569976
TI  - Responsibility for statistical analyses.

PMID- 14569977
TI  - Abstracts of the 2003 International Conference on Eating Disorders Clinical and
      Scientific Challenges: The Interface between Eating Disorders and Obesity. May 29
      31, 2003. Denver, Colorado, USA.

PMID- 14569978
TI  - Eight eye muscle surgical treatment in a patient with acquired nystagmus and
      strabismus: a case report.
AB  - The purpose of this paper is to outline the clinical benefits and
      electrophysiological changes after extraocular muscle surgery for acquired
      nystagmus and strabismus in an adult patient. a 41-year-old Caucasian female
      suffered from oscillopsia, bilateral cranial nerve IV palsies, and vertical
      nystagmus. Medical therapy was ineffective. She underwent bilateral, eight muscle
      surgical procedure which included: tenectomies of the superior oblique OU,
      myectomies of the inferior oblique OU, recessions of the medial rectus muscles OU
      (with OD on a post-operatively adjustable suture), and differential recessions of
      the superior rectus muscles OU. This provided marked improvement in her symptoms.
      These results suggest that surgery for acquired nystagmus can affect an
      improvement in the characteristics of the nystagmus that result in visual
      complaints. Combining "nystagmus surgery" plus strabismus surgery may be a viable
      option in some adult patients with acquired nystagmus who are unresponsive to
      medical therapy.

PMID- 14569979
TI  - Should consensus be 'the commission method' in the US? The perspective of the
      Federal Advisory Committee Act, regulations, and case law.
AB  - This paper examines the drive for consensus from the perspective of the good
      government framework for federal advisory commissions in the United States.
      Specifically, the paper examines the Federal Advisory Committee Act (FACA)--the
      statute, its regulations, and case law. It shows that the FACA was intended to be
      an antidote to abuses in consensus-making processes, including the failure to
      fully include competing views on commissions. The index of suspicion in the FACA
      scheme rises when a group work product--including a consensus report--is to be
      the basis of recommendations to federal officials. Once FACA's requirements
      regarding committee composition are satisfied, the index of suspicion drops and
      FACA is indifferent to consensus-making; but the conditions for informed,
      meaningful participation apply to members who dissent from, as well as those who
      participate in, consensus. In negotiated rulemaking, the push for consensus and
      closure creates unacceptable tension with the good government goals of openness
      and accountability. Proponents of consensus-only bioethics commissions can learn
      from FACA-related legislative, agency, and judicial insights that consensus
      seeking is not always desired by government officials; is rarely cost free; and
      that diversity and dissent enhance openness, accountability, and fairness. The
      burden of proof is therefore on proponents of a consensus-only standard for
      bioethics commissions to demonstrate that a drive for consensus furthers sound
      decision-making by government officials more than it sets back openness and
      accountability to a diverse public.

PMID- 14569980
TI  - [A ballet dancer after os trigonum excision].

PMID- 14569981
TI  - Interpretation of home blood glucose monitoring.

PMID- 14569982
TI  - The role of national ethics commissions in Finland.
AB  - There are six national ethics commissions in Finland. The National Advisory Board
      on Research Ethics was first established in 1991, followed by the National
      Advisory Board on Biotechnology and the Board on Gene Technology in 1995. The
      National Advisory Board on Health Care Ethics was established in 1998, followed
      by its Sub-Committee on Medical Research Ethics in 1999. The Co-operation Group
      for Laboratory Animal Sciences was established in 2001. Only the Board on Gene
      Technology works as a national authority and gives binding opinions and
      recommendations about the use of genetically modified organisms. The Sub
      Committee on Medical Research Ethics acts a national research ethics committee
      and gives opinions about research projects. Other advisory boards do not make
      legally binding decisions, but their expertise gives a lot of power to their
      opinions and statements. The commissions work in close collaboration with each
      other, having regular meetings. They arrange seminars and conferences, and share
      information with each other. The commissions also share duties and information in
      international collaboration. How the voice and opinions of these commissions is
      heard in society lies in the wide, multi-professional expertise of their members.
      Large commissions and wide expertise may make it difficult to find consensus in
      their opinions and statements, although wide expertise may, more than discussion
      in a small expert group, help to further process difficult ethical issues.
      Collaboration between different bodies is important in order to share duties, and
      also to add more emphasis to the statements and opinions where different bodies
      share interests. In our country, the interest that national commissions share is
      research ethics, where the advisory boards and their members have discharged
      collaborative activities for years.

PMID- 14569983
TI  - Report of the 75 Annual Meeting of the Association for Research in Vision and
      Ophthalmology (ARVO), Fort Lauderdale, Florida. May 4-9, 2003.

PMID- 14569984
TI  - [Surgical infections].

PMID- 14569985
TI  - The myeloproliferative sarcoma virus causes transformation or erythroid
      progenitor cells in vitro.
AB  - The myeloproliferative sarcoma virus induces spleen focus formation in vivo and
      transforms fibroblasts in vitro. We showed in this study that in vitro infection
      of spleen or bone marrow cells from susceptible mice with the myeloproliferative
      sarcoma virus leads to the formation of erythroid bursts. Under optimal
      conditions erythroid bursts formed in the absence of added erythropoietin, but
      the addition of as little as 0.05 U of erythropoietin per ml to infected cultures
      resulted in a significant increase in numbers of erythroid bursts and the
      proportion of hemoglobinized cells. A comparison of the kinetics of burst
      formation and the size of the induced bursts with those induced with Friend virus
      suggested that either sarcoma virus such as the myeloproliferative sarcoma virus
      or the target cells for the two viruses were not the same. Density
      characterization and heat lability studies indicated that the increased erythroid
      proliferation in vitro was a virus-induced event, but the possibility that the
      induced erythroid burst formation is mediated via interaction with a nonerythroid
      target cell and subsequent release of a soluble factor cannot be ruled out.

PMID- 14569986
TI  - [Duties of patient information--medical and legal aspects].

PMID- 14569987
TI  - Assessing benefits in clinical research: why diversity in benefit assessment can
      be risky.

PMID- 14569988
TI  - The subject advocate: protecting the interests of participants with fluctuating
      decisionmaking capacity.

PMID- 14569989
TI  - Informing study participants of research results: an ethical imperative.

PMID- 14569991
TI  - Analytical procedures for measuring safety levels of dioxins, furans and PCBs.

PMID- 14569990
TI  - Should smallpox vaccine be made available to the general public?
AB  - In June 2002, the Advisory Committee on Immunization Practices (ACIP) approved
      draft recommendations concerning preparation for potential biological terror
      attacks that utilize the smallpox virus. ACIP recommends against both mandatory
      and voluntary vaccination of the general public. The present paper examines the
      moral and political considerations both for and against each of the general
      public vaccination options considered by the ACIP in the context of the state's
      authority over vaccination for the purposes of protecting public health. Although
      it is clear that compulsory mass vaccination is not justified at this time, the
      issues surrounding voluntary vaccination are more complex. Should smallpox
      vaccination prior to an outbreak be made available to the general public? The
      paper concludes that the vaccine should not be made available at this time. This
      conclusion, however, is based upon contingent features of current circumstances,
      which would change once an outbreak occurred. In the even of a terror-related
      outbreak of smallpox, the general public's access to voluntary vaccination would
      become justified, even in areas beyond where the outbreak has occurred.

PMID- 14569992
TI  - [Oxaliplatin: high activity at all stages of colon carcinomas].

PMID- 14569993
TI  - [6. Mini symposium Xenotransplantation. D-Berlin, Robert-Koch-Institute, May 9,
      2003].

PMID- 14569994
TI  - [TVT seminar about animal experimentation committees. D-Darmstadt, June 13,
      2003].

PMID- 14569995
TI  - Intrinsic conflicts of interest in clinical research: a need for disclosure.
AB  - Protection of human subjects from investigators' conflicts of interest is
      critical to the integrity of clinical investigation. Personal financial conflicts
      of interest are addressed by university policies, professional society
      guidelines, public standards, and government regulation, but "intrinsic conflict
      of interest"--conflicts of interest inherent in all clinical research--have
      received relatively less attention. Such conflicts arise in all clinical research
      endeavors as a result of the tension among professionals' responsibilities to
      their research and to their patients and both academic and financial incentives.
      These conflicts should be disclosed to research subjects and managed as
      assiduously as are financial conflicts of interest.

PMID- 14569996
TI  - Methods of substitution in laparoscopic surgical training.

PMID- 14569998
TI  - [Animal experimentation in Switzerland 2002: in college it was done "like
      wild"!].

PMID- 14569997
TI  - Rehabilitating equipoise.
AB  - When may a physician legitimately offer enrollment in a randomized clinical trial
      (RCT) to her patient? Two answers to this question have had a profound impact on
      the research ethics literature. Equipoise, as originated by Charles Fried, which
      we term Fried's equipoise (FE), stipulates that a physician may offer trial
      enrollment to her patient only when the physician is genuinely uncertain as to
      the preferred treatment. Clinical equipoise (CE), originated by Benjamin
      Freedman, requires that there exist a state of honest, professional disagreement
      in the community of expert practitioners as to the preferred treatment. FE and CE
      are widely understood as competing concepts. We argue that FE and CE offer
      separable and, in themselves, incomplete justifications for the conduct of
      clinical trials. FE articulates conditions under which the fiduciary duties of
      physician to patient may be upheld in the conduct of research. CE sets out a
      standard for the social approval of research by institutional review boards.
      Viewed this way, FE and CE are not necessarily competing notions, but rather
      address complementary moral concerns.

PMID- 14569999
TI  - Bibliography. Current world literature. Bladder cancer.

PMID- 14570000
TI  - Bibliography. Current world literature. Andrology and sexual dysfunction.

PMID- 14570001
TI  - [On the etymology and the semantics of the medical term: Istiska'].
AB  - This article deals with the etymology and semantics of the term istiska' which
      was interpreted as cirrhosis in some studies. The meaning of the term in the old
      medical texts and dictionaries was studied by quoting examples from original
      sources. It is concluded that istiska was used for dropsy, that is, an abnormal
      accumulation of serous fluid in tissue or in a cavity of a body, such as the
      abdomen, pleura, thorax, peritoneum etc.; and in the 19th and 20th centuries it
      meant hydrax and, was used as the prefix hydr- or hydro-. The text also describes
      the various forms of istiska' found in the Turkish terminology.

PMID- 14570002
TI  - Persistent vegetative state, prospective thinking, and advance directives.
AB  - This article begins with a discussion of persistent vegetative state (PVS),
      focusing on concerns related to both diagnosis and prognosis and paying special
      attention to the 1994 Multi-Society Task Force report on the medical aspects of
      PVS. The article explores the impact of diagnostic and prognostic uncertainties
      on prospective thinking regarding the possibility of PVS and considers the
      closely related question of how prospective thinkers might craft advance
      directives in order to deal most effectively with this possibility.

PMID- 14570004
TI  - Fingerprinting the colon?

PMID- 14570003
TI  - [Two Turkish manuscripts on gems (jauhar) and the treatment by means of gems].
AB  - Literary works of the genre called cevahir-name or cevher-name are written in
      order to give information on how gems (cevher-jauhar) are formed, where they are
      found, their estimated values, how to distinguish them from the imitations, what
      their particular colours are and on their uses and harmful effects. These
      literary works are sometimes titled in accordance with the genre they belong to
      and sometimes they are given different titles. The literary works dealing with
      the subject of cevher are mostly written in prose and only a few of them are in
      verse. The Turkish versions of cevahir-name texts started to be written in the
      15th century. These texts, covering the earlier knowledge of medicine, give
      information on gems and perfumes; how they effect human health; and the way they
      should be used in medical treatment. Therefore, these texts should be discussed
      in relation with their place in the history of Turkish science. Two cevahir
      names, which were translated into Turkish by Mustafa bin Seydi and Za'ifi in the
      15th and 16th centuries are still available. The translations by Mustafa bin
      Seydi and Za'ifi, did not only convey the classical and medieval knowledge on
      cevhers to the contemporary readers, but they also confirm the fact that this
      information was a part of the Ottoman social life.

PMID- 14570005
TI  - The professor Constantinos Caratheodory (1802-1879) - His biography by Spyridon
      Mavrogeni Pasha.

PMID- 14570006
TI  - [Mental diseases described in "Seririyat-i Akliye Desleri", a work of Rasit
      Tahsin (Tugsavul)].
AB  - Resit Tahsin (Tugsavul) is a well known Turkish psychiatrist. He was sent to
      Germany to study psychiatry and neurology and on his return he started to lecture
      in the Military Faculty of Medicine. Thus, courses on neurology and psychiatry,
      formerly carried out under the title of "asabiye", as a part of the internal
      medicine courses, became an independent course called "Emraz-i Akliye ve
      Asabiye". Resit Tahsin's book "Seririyat-i Akliye Dersleri" was published in 1336
      (1920). The book consists of two parts; and in the first part, mental diseases
      are classified and dealt with. In the foreword, Resit Tahsin, notes that, in
      composing the first part of his book, he utilized a book of Emil Kraepelin whom
      he had worked with in Germany. The second part of the book is devoted to cases
      presented to the medical students. The history of each case, observations of the
      patients and their diseases, the method of differentiating diagnosis and the
      prognosis and treatment of diseases are discussed. In the foreword, the author
      also states that he disregarded the usual composing of medical books of his time;
      and he preferred to write his book as cynical lectures, after the way in Europe.
      He adds that be expected this to be an example for books similar to those written
      by "European masters". In the introduction, the need for and the aim of education
      on mental diseases is explained. Detailed information on the social aspects of
      psychiatric patients is also given. This book consists of 56 lectures to medical
      students and meanwhile it provides information about the psychiatry education
      during the period.

PMID- 14570007
TI  - UC for UC: ursodiol chemoprevention for ulcerative colitis.

PMID- 14570008
TI  - Revisiting the problem of Jewish bioethics: the case of terminal care.
AB  - This paper examines the main Jewish sources relevant to end-of-life ethics, two
      Talmudic stories, the early modern code of law (Shulhan Aruch), and contemporary
      Halakhaic (religious law) responsa. Some Orthodox rabbis object to the use of
      artificial life support that prolongs the life of a dying patient and permit its
      active discontinuation when the patient is suffering. Other rabbis believe that
      every medical measure must be taken in order to prolong life. The context of the
      discussion is the most recent release of the "Steinberg Report," which proposes a
      law regulating end-of-life issues in Israel. It is argued that the Orthodox
      rabbis base their views on a strongly positivist concept of religious law. The
      rabbis deliberate the law as a manifestation of the will of God and try to
      stretch the law as much as possible in order to benefit the patient, even when it
      is good for the patient to die. Direct and active actions that kill are
      prohibited; certain forms of passive euthanasia and contrivances that terminate
      life support without needing direct human action are accepted.

PMID- 14570010
TI  - Making a good thing last: the effect of intravenous hydrocortisone premedication
      on the immunogenicity of infliximab.

PMID- 14570009
TI  - [Preventive measures taken in Adrianople during the 1893-1894 cholera epidemic,
      as reflected in a local newspaper].
AB  - Cholera is derived from the Latin words colos (large intestine) and reo (to flow)
      and means flowing of the liquids through the stomach and the intestines. The
      first cholera epidemic was experienced in India and spread out to other
      countries. Although it had been known for ages, it was not recognized until the
      16th century. Seven serious cholera epidemics have broken out in the world since
      the 19th century. In spite of all precautions taken by the Ottoman government,
      the sixth world cholera epidemic that started in Asia in 1891 and caused the loss
      of 40 thousand people, reached Istanbul in 1893. Later, it spread to Iznik,
      Salonika and Anatolia. Just as it appeared in Europe, precautions started to be
      taken in Adrianople. At first, special care was taken for city hygiene and a
      commission was formed to inspect the cleanliness of the city. Many brochures and
      articles were published on the protection against the illness, in order to inform
      the citizens of the cholera epidemic. Preachers spoke of cholera in their
      sermons. To protect Adrianople against the epidemic, entrance into and exit out
      of the city were patrolled and passengers coming from Europe or Istanbul to
      Adrianople were kept waiting for three days at the quarantines built in Cisri
      Mustafa Pasha and Catalca.

PMID- 14570011
TI  - [Ancient Indian and Chinese medical oaths and the comparison of their medical
      rules].
AB  - The art of medicine has existed on earth since the existence of mankind. Although
      the traditions and practices may vary, the mere intention has been to help people
      remain healthy and restore their health when they get sick. Since health is man's
      most important fortune, the medical profession has always been open to abuse or
      misuse. To prevent this, it came to be a tradition to bound health care
      professionals with oaths and codes. This article examines medical oaths and codes
      in two different Eastern traditions, namely China and India. Two different
      medical oaths from two major ancient Indian medical books, Charaka Samhita and
      Susuruta will be addressed and elaborated. They will be compared and contrasted
      with each other and their commons and differences from the other medical oaths
      will be examined. Chinese medical codes, one from the 7th and the other from the
      17th century are reviewed in the article. It has appeared from the discussion
      that although there are some 'unchangeables' in the codes and oaths, like the
      reference to some sacred or transcendental being or commitment to show respect to
      the teachers, there are differences due to the time and place. It is also
      interesting to note how medical practice and its values are influenced by the
      respective society.

PMID- 14570012
TI  - The importance of penetration.

PMID- 14570013
TI  - [A bibliographical study on the hospitals of the Ottoman period].
AB  - This is a bibliography of the articles and books about the hospitals founded
      during the Ottoman empire period and it includes all of the related publications
      as well.

PMID- 14570014
TI  - Conscription of cadaveric organs for transplantation: neglected again.
AB  - The March 2003 issue of the Kennedy Institute of Ethics Journal was devoted to
      cadaveric organ procurement. All the discussed proposals for solving the severe
      organ shortage place a higher value on respecting individual and/or family
      autonomy than on maximizing recovery of organs. Because of this emphasis on
      autonomy and historically high refusal rates, I believe that none of the
      proposals is likely to achieve the goals of ensuring an adequate supply of
      transplantable organs. An alternative approach, conscription of cadaveric organs
      for transplantation, reverses the rank order of these priorities by placing
      greater value on maximizing recovery of organs than on respect for autonomy.
      Although conscription of organs initially may appear to be a radical and even
      ridiculous proposal, careful consideration reveals that it might well solve the
      organ shortage in an ethically acceptable way.

PMID- 14570015
TI  - [Health policy of the Republic of Turkey in accordance with the Minutes of the
      Turkish Parliament (part I)].
AB  - Because of the invasion of the Ottoman territory after the World War I, the
      Turkish War of Liberty was initiated by Mustafa Kemal Pasha and his friends.
      While they aimed at a successful outcome of the battle, they at the same time
      tried to achieve a nation-wide organization. In order to look after the nation's
      medical and social service, on May 2nd 1920, a new ministry called the Ministry
      for Medical and Social Service was founded. The new ministry's task was not only
      to concern itself with the medical and social service, but also with immigration
      and of the immigrants. At the beginning the hitherto existing social system and
      certain laws were not abolished until they were replaced by new ones in order to
      prevent an interruption in the social service. In these years the aim of the
      social system was to struggle against infectious diseases, to prevent infections,
      to decrease infant mortality and to increase the population, to take measures
      against diseases from abroad, to pass the laws needed and to form a central
      authority. Besides these laws which were directly related with the medical and
      social service during the War of Liberty, the governing of the districts and the
      regulations concerning the miners in Zonguldak were passed in order to protect
      peoples' health. Our political existence was confirmed through the signing of the
      agreement reached by the Lausanne Conference after the War of Liberty and
      consequently the Medical Care Supreme Council of Istanbul, which had continued
      its validity as a capitulation, was abolished. The social state policy of the
      period which had started with the foundation of the Turkish Republic aimed to
      extend the state's medical staff, continue the employment of the health personnel
      specialized in medicine, struggle against infectious diseases in an organised
      way, provide a wide-spread medical service, give priority to preventive health
      care and establish medical institutions, effect a cooperation of these
      institutes, pass the necessary laws and establish state supervision in all
      fields. In the first ten years of the Republic, new schools and courses were
      started in order to increase the number of the medical staff to be sent to areas
      deprived of social service. In accordance with the Obligatory Service Law of
      1923, doctors who were sent to eastern Turkey were provided with encouraging
      advantages. The organizational work and the laws concerning infectious diseases
      like malaria, syphilis and trachoma, which were wide-spread, was effective and
      successful from the year 1925 onwards when Dr. Refik Saydam was the Minister for
      Health. The meetings of the Turkish National Congresses on Medicine helped solve
      the nation's health problems and influenced the state's policy and the Health
      Ministry's activities. The aim was not merely the protection of peoples' health
      through education. In this period, many laws were passed with the aim to protect
      the nation's health and to ensure state control in every field. Some of these are
      still in force today. Besides the medical treatment of the poor and the old, laws
      of validity for a long period, which were effective in the protection of the
      health of children, the adolescent and the pregnant women in the social life and
      employment, were passed. In the first ten years of the Republic a protective,
      comprehensive and human health policy was observed in accordance with the policy
      of the state.

PMID- 14570016
TI  - Abstracts of the 68th Annual Meeting of the American College of Gastroenterology.
      October 10-15,, 2003. Baltimore, Maryland, USA.

PMID- 14570017
TI  - [Dermatological diseases and treatment described in the Turkish manuscripts (XIV
      XVth centuries) (part II)].
AB  - This study deals with skin diseases described in the earliest compiled or
      translated Turkish medical manuscripts of the 14th and 15th centuries in
      Anatolia. The manuscripts studied are: Muntehab-i Sifa, Edviye-i Mufrede,
      Tervihu'l-Ervah, Yadigar, Cerrahiyyetu'l-Haniyye, Kamilu's-Sinaatu't-Tibbiye
      Tercu-mesi, Kitab-i Muntehab-i fi't-Tibb, Haza'inu's-Sa'adat, Akrabadin
      Tercumesi, Mucerrebname, Mufredat-i Ibn-i Baytar Tercumesi, Tuhfe-i Mubarizi and
      Tuhfe-i Muradi. The skin diseases known at that time are studied under the
      following topics: Cuderi (Cicek, Variola, Small-pox); Hasbe (Kizamik, Rubeola,
      Measles); Cuzzam (Lepra, Leprosy, Hansen's disease); Demregu (Temriye,
      Dermatophtosis, Tinea corporis); Behak (There are two types: the white and the
      black; the black is Addison's disease); Baras (Ala, Vitilio); Nemle (Isirga,
      Makul); Ates paresi (Nar-i farisi, frunculosis); Cemre (Kara kabarcik, Sirpence,
      Karbonkul, Carbuncle); Caversiye (Kabarcik hastaligi, blisters disease);
      Sivilceler (Various types of pimples; Humre: Yilancik, Erizipel, Erysipelas, St.
      Anthony's fire; Basbert: Ciban, Fronkul, Boil, Fruncle; Dummel: Kan cibani, Abse,
      Abscess); Abile (Kabarcik, Bule); Seretan (Kanser, Cancer); Hanazir (Siraca,
      Scrofuloderma); Akile (Yinurbas, Gangren); Kurdesen (Urtiker, Urticeria); Uyuz
      (Gale, Scabies); Giciyik (Kasinti, Pruritus); Sa'fe (Konak, Seboreik dermatit,
      Scurf; Kel (Alopesi, Favus); Evram (Sisler, Urlar, Tumours); Yara (Karha,
      Cerahat, Wound). The terminology and symptoms of these diseases are studied and
      tried to find their equivalents of today. The causes and the treatment of the
      skin diseases known then are presented. The second part of Tokac's article
      continues to deal with the etiology, symptoms and treatment of dermatological
      diseases.

PMID- 14570018
TI  - Abstracts of the 53rd Annual Meeting of the American Society of Human Genetics.
      November 4-8, 2003. Los Angeles, California, USA.

PMID- 14570019
TI  - Dilemmas in military medical ethics since 9/11.
AB  - The attack on the United States by terrorists on 9/11 and the war with Iraq have
      raised new ethical questions for the military and for military physicians (Herman
      2002; Elshtain 2003). How and when attacks may occur now is less predictable.
      Planes have been hijacked, and persons dressed as civilians may carry bombs to
      blow themselves and others up. These dangers pose an increased threat, and, thus,
      there is a need for new defensive measures. How far these measures should go is,
      however, greatly open to debate. One of the most difficult ethical question
      raised for the military and military doctors by these developments is what
      interrogation methods are permissable when questioning captured terrorists. The
      licitness of different interrogation practices is, however, only one of the
      ethical problems potentially encountered by military physicians now having to
      treat terrorists and POWs. The following discussion presents the major concerns
      regarding this and other issues.

PMID- 14570020
TI  - [A systematic analysis of the Ottoman Red Crescent periodical (part II)].
AB  - Founded in 1877, the Ottoman Red Crescent Society rendered a lot of important
      services in military and civil areas in the Ottoman Empire. The Ottoman Red
      Crescent Society not only gave health services for the soldiers, but it also
      attempted to obey the international acts signed for the captives and to rescue
      them together with the countries involved under the supervision of the
      international Red Cross. In the civilian area, the Ottoman Red Crescent Society
      also played an active role to meet the casualties' needs, such as food, clothes,
      and accommodation following natural disasters like earthquake, flood, fire etc.
      Ottoman Red Crescent Society published a monthly newsletter called Osmanli Hilal
      i Ahmer Mecmuasi to announce its services more effectively to the public since 15
      September 1921 (12 Muharrem 1340). The publication of the newsletter continued as
      Turkiye Hilal-i Ahmer Mecmuasi after the 15th issue. Starting with the 85th issue
      on September 15th, 1928 (30 Rebiulevvel 1347) it was printed with Latin alphabet
      instead of Arabic letters. A brief translation in French and in English exist in
      the end of each issue. In the second part of this research, news about the Red
      Crescent Society's organization; financial supports for the Society and, in
      return, material and financial aids by she Society; local organizations providing
      aid to the Society; money collected during Bairams; plays and balls arranged by
      the Society; and the activities of the womens' branch of the Red Crescent
      Society, are introduced.

PMID- 14570021
TI  - [The Tarihu'l-Etibba by Ishak bin Huneyn].
AB  - This is a translation of Rosenthal's article on Ishak b. Hunayn's Tarih al
      Atibba, into Turkish. It also includes Ioannes Philoponos's (John Philoponos or
      Yahya en-Nahvi chronology of physicians. The article deals with the chronology of
      ancient physicians from the beginning to the year 290 of the Hegira and their
      views on the sources of medicine. The translator contributes by means of foot
      notes.

PMID- 14570022
TI  - [Use of phyto-estrogens after breast cancer: yes but...].

PMID- 14570023
TI  - [The 15th anniversary of Ord. Prof. Dr. Suheyl Unver's death].
AB  - Selections from the inauguration speeches during the anniversaries of Ord. Prof.
      Dr. Suheyl Unver's death and the ceremonies organized on the occasion of the
      Suheyl Unver Atelier's proficiency certificate awards are introduced.

PMID- 14570024
TI  - [Use of phyto-estrogens after breast cancer: against the prescription of phyto
      estrogens in cases of previous breast cancer].

PMID- 14570025
TI  - Health plan good "catch" for fishing industry.

PMID- 14570026
TI  - [The biography and work of Prof. Dr. Burhaneddin Toker-on the occasion of the
      50th anniversary of his death].

PMID- 14570027
TI  - Abstracts of the Southern Medical Association's 97th Annual Scientific Assembly.
      Atlanta, Georgia, USA. November 6-8, 2003.

PMID- 14570028
TI  - Economics of enforcement.

PMID- 14570029
TI  - New arrival: CERHR monograph series on reproductive toxicants.

PMID- 14570030
TI  - NIEHS fights fat.

PMID- 14570031
TI  - [Abstracts of the 101st Meeting of the German Ophthalmology Society. 25-28
      September 2003, Berlin].

PMID- 14570032
TI  - US and UK researchers share Nobel prize. Paul C Lauterbur and Peter Mansfield
      share award for seminal work on MRI.

PMID- 14570033
TI  - Tobacco carcinogens, their biomarkers and tobacco-induced cancer.
AB  - The devastating link between tobacco products and human cancers results from a
      powerful alliance of two factors - nicotine and carcinogens. Without either one
      of these, tobacco would be just another commodity, instead of being the single
      greatest cause of death due to preventable cancer. Nicotine is addictive and
      toxic, but it is not carcinogenic. This addiction, however, causes people to use
      tobacco products continually, and these products contain many carcinogens. What
      are the mechanisms by which this deadly combination leads to 30% of cancer
      related deaths in developed countries, and how can carcinogen biomarkers help to
      reveal these mechanisms?

PMID- 14570034
TI  - Abstracts of the 16th Annual Congress of the European Society of Intensive Care
      Medicine. 5-8 October 2003, Amsterdam, Netherlands.

PMID- 14570035
TI  - UN steps up action on traditional knowledge.

PMID- 14570036
TI  - Drug addiction and HIV infection on rise in Tajikistan.

PMID- 14570037
TI  - Cannabinoids: potential anticancer agents.
AB  - Cannabinoids - the active components of Cannabis sativa and their derivatives -
      exert palliative effects in cancer patients by preventing nausea, vomiting and
      pain and by stimulating appetite. In addition, these compounds have been shown to
      inhibit the growth of tumour cells in culture and animal models by modulating key
      cell-signalling pathways. Cannabinoids are usually well tolerated, and do not
      produce the generalized toxic effects of conventional chemotherapies. So, could
      cannabinoids be used to develop new anticancer therapies?

PMID- 14570038
TI  - Report details lessons from SARS outbreak.

PMID- 14570039
TI  - WHO lowers figures on SARS infections.

PMID- 14570040
TI  - The role of Notch in tumorigenesis: oncogene or tumour suppressor?
AB  - Notch signalling participates in the development of multicellular organisms by
      maintaining the self-renewal potential of some tissues and inducing the
      differentiation of others. Involvement of Notch in cancer was first highlighted
      in human T-cell leukaemia, fuelling the notion that aberrant Notch signalling
      promotes tumorigenesis. However, there is mounting evidence that Notch signalling
      is not exclusively oncogenic. It can instead function as a tumour suppressor.

PMID- 14570041
TI  - FDA homes in on counterfeit and imported drugs.

PMID- 14570042
TI  - France announces plan for improved emergency services.

PMID- 14570043
TI  - Cancer chemoprevention with dietary phytochemicals.
AB  - Chemoprevention refers to the use of agents to inhibit, reverse or retard
      tumorigenesis. Numerous phytochemicals derived from edible plants have been
      reported to interfere with a specific stage of the carcinogenic process. Many
      mechanisms have been shown to account for the anticarcinogenic actions of dietary
      constituents, but attention has recently been focused on intracellular-signalling
      cascades as common molecular targets for various chemopreventive phytochemicals.

PMID- 14570044
TI  - Africans advocate antiretroviral strategy similar to DOTS. AIDS experts suggest
      community health workers should help in the delivery of antiretroviral drugs.

PMID- 14570045
TI  - New tools for functional mammalian cancer genetics.
AB  - Knowledge of the function of individual genes that encode components of cell
      signalling pathways is crucial to our understanding of normal growth control and
      its deregulation in cancer, but we have functional information for only 15% of
      human genes at present. Several new technologies have recently become available
      to identify gene function in mammalian cells using high-throughput genetic
      screens. These new tools will make it possible to identify new and innovative
      classes of anticancer drugs, including those that show synthetic lethal
      interactions with cancer-specific mutations.

PMID- 14570047
TI  - [Proceedings of the Spring Meeting of Internal Medicine. Lille, France, 23-24
      March 2003].

PMID- 14570046
TI  - Proteomic analysis of cancer-cell mitochondria.
AB  - Mitochondrial dysfunction and mutations in mitochondrial DNA have been frequently
      reported in cancer cells. Mitochondrial gene-expression signatures of transformed
      cells have been identified; however, the phenotypic effects of these genetic
      alterations remain to be established. Identification of mitochondrial proteins
      that are aberrantly expressed in cancer cells has been made possible by the
      recent development of mitochondrial functional proteomics and could identify new
      markers for early detection and risk assessment, as well as targets for
      therapeutic intervention.

PMID- 14570048
TI  - Abstracts of Conference of Plant Stress, Reactive Oxygen and Antioxidants.
      Freising-Weihenstephan, Germany, September 10-13, 2003.

PMID- 14570050
TI  - Cancer in Africa: epidemiology and prevention.

PMID- 14570049
TI  - The nuclear pore complex: nucleocytoplasmic transport and beyond.
AB  - Over the past two years, it has become evident that there is an unexpected link
      between nuclear pore complex structure and dynamics, nucleocytoplasmic transport
      and chromosome segregation. In addition, a tomographic three-dimensional
      reconstruction of native nuclear pore complexes preserved in thick amorphous ice
      has unveiled a number of new structural features of this supramolecular machine.
      These data, together with some of the elementary physical principles that
      underlie nucleocytoplasmic transport, will be discussed in this review.

PMID- 14570051
TI  - [An analysis of appearance frequency of formulations and crude drugs in Jin-Kui
      Yao-Lue].
AB  - A systematic database was constructed to examine the frequency of appearance of
      individual formulations and crude drugs in Jin-Kui-Yao-Lue, a traditional Chinese
      formulary used for miscellaneous chronic internal diseases. This formulary
      contains 263 kinds of genuine formulations, but because of overlapping or
      repetition, the total number of formulations mentioned is as high as 309. It was
      proved that among the 212 kinds of crude drugs described in Jin-Kui-Yao-Lue, the
      five crude drugs most frequently mentioned are Glycyrrhizae Radix, Cinnamomi
      Ramulus, Zhingiberis Rhizoma, Zizyphi Fructus and Paeoniae Radix, which are used
      in Guizhi-tang, Keishi-to in Japanese. Mel used for preparing pills appears more
      frequently in Jin-Kui-Yao-Lue than in Shang-Han-Lun, which is the most commonly
      Chinese medical formulary referred to for treatment of acute externally
      contracted diseases. The ways of using Astragali Radix, Sinomeni Caulis et
      Rhizoma, Moutan Cortex and Cnidii Rhizoma described in Jin-Kui-Yao-Lue differ
      from that described in Shang-Han-Lyn. Furthermore, the directions for using
      Pinelliae Tuber for cold-phlegm syndrome and Poria for dampness-retention
      syndrome are developed in Jin-Kui-Yao-Lue.

PMID- 14570052
TI  - [Abstracts of the 5th Meeting of the Nephrology Society and the Francophone
      Society of Dialysis. Nancy, France, 30 September-3 October 2003].

PMID- 14570053
TI  - Ras GTPases: integrins' friends or foes?
AB  - Integrins are cell-surface receptors that mediate and coordinate cellular
      responses to the extracellular matrix (ECM). Cellular signalling pathways can
      regulate cell adhesion by altering the affinity and avidity of integrins for ECM.
      The Ras family of small G proteins, which includes H-ras, R-ras and Rap, are
      important elements in cellular signalling pathways that control integrin
      function.

PMID- 14570054
TI  - [A 50-year history of new drugs in Japan-the development and progress of anti
      diabetic drugs and the epidemiological aspects of diabetes mellitus].
AB  - The development and progress of antidiabetic drugs (e.g., insulin preparations
      and hypoglycemic drugs) are retrospectively investigated in Japan. Their
      influences on the treatment of diabetes mellitus (DM) and its epidemiological
      aspects are also discussed. 1) Insulin preparations: Insulin was introduced for
      DM therapy in 1925, two or three years after its discovery in Canada. The
      preparations were raw extracts of bovine or porcine pancreas. These did not
      prevail widely in Japan because of the low incidence of DM before World Wan II.
      After the war, a shortage of mammalian materials compelled the use of fish
      pancreatic tissues such as bonito and/or tuna for insulin production. Insulin
      infection, so-called regular insulin, was first promoted in the 6th
      "Pharmacopoeia Japonica" (JP6) in 1951 and has been maintained to the present
      edition (JP14, 2001). Although depot-type insulin preparations were developed in
      the USA and Europe during the war, the introduction of those preparations to
      Japan was delayed until 1951, when Protamine zinc insulin appeared. Globin zinc
      insulin and Isophane insulin were introduced for clinical use in 1952 and 1955,
      respectively. These were also adopted for JP7 (1961). Biphasic-type insulin,
      which has a rapid onset and long duration of activity, appeared in 1965. Purified
      preparations from bovine or porcine sources have been available since 1980, which
      might be a strong reason for the decrease in insulin allergy. Insulin from animal
      origin has been supplied for almost 60 years since its discovery. Amino acid
      sequences of insulins from various species of animals were determined by the
      pioneering studies of Sanger and his associates. Human insulin, which differs
      from porcine insulin by only one amino acid, was produced by Novo researchers in
      1982 using a semi-synthetic method. Then the Lilly group soon succeeded in
      obtaining human insulin by recombinant DNA technology in the same year. Both
      products were introduced to Japan in 1985, and the recombinant products prevailed
      throughout the 1990s. Human insulin analogues (i.e., Insulin lispro and Insulin
      aspart) appeared in 2001. These are applied for after-meal glycosmia owing to
      their ultrarapid onset of activity. Self-injection by DM patients was legalized
      in 1981. To make the infection technique sure and easy, cartridge (pen-type) and
      disposable kit-type needles were devised in the 1990s. 2) Oral hypoglycemic
      drugs: Instead of the exclusive parenteral usage of insulins, there was also
      demand for oral dosage forms. The first of the sulfonyrlurea (SU) group, BZ-55,
      was used for DM clinically in 1955 in Germany. But it was soon withdrawn because
      of its antibacterial action. This led to the development of various SU groups.
      Tolbutamide (1956), chlorpropamide (1959), acetohexamide (1964) and tolazamide
      (1961) were introduced to Japan as first-generation SUs. Then glyclopyramide
      (Kyorin, 1965), glybenclamide (1971), gliclazide (1984) and glimepiride (1999)
      appeared as the second-generation SUs. These were used orally for Type 2
      diabetes. Biguanide (BG) group, phenformin HC1 (1959), metformin HC1 (1961) and
      buformin HC1 (1961) had also been in use by oral treatment of Type 2 diabetes. SU
      appears to act by increasing the sensitivity of b-cells, which secrete insulin.
      BG probably exerts by increasing glucose transport across the membranes of target
      organs. 3) New types of antidiabetic drugs: a-Glucosidase inhibitors (i.e.,
      acarbose: Bayer, 1993; and voglibose: Takeda, 1994) act on hyperglycemia after
      meals by decreasing glucose absorption. Thiazolidinedione compounds, such as
      troglitazone (Sankyo, 1995) and pioglitazone HC1 (Takeda, 1994) act by increasing
      the insulin sensitivity of the target tissues. These are useful for Type 2 DM
      patients when SUs are ineffective. Nevertheless, troglitazone was discontinued in
      2000 due to severe liver damage. Nateglinide (Ajinomoto Co., 1999), which is a D
      phenylalanine derivative acting similar to SUs, is useful orally for after-meal
      hyperglycemia of Type 2 diabetes. Epalrestat (Ono Yakuhin Co., 1992) is effective
      for diabetic neuropathy by reducing the formation of sorbitol. These anti-DM
      drugs were recently studied and developed in Japan. 4) The Japan Diabetes Society
      proposed a guideline on diagnostic criteria and treatment of diabetes mellitus
      (DM) in 1999 and revised it in 2002. DM is classified as insulin-dependent DM
      (Type l) and non-insulin dependent DM (Type 2). Type 1, juvenile onset DM,
      requires insulin therapy to prevent ketosis and to sustain life. Treatment of
      type 2, adult onset DM, is recommended as a step-by-step method, starting with
      dietary-exercise therapy, followed by oral hypoglycemic drugs and then insulin
      therapy. DM patients with complications should have a therapy devised to match
      their circumstances. 5) Epidemiological aspects: The mortality rate of DM
      compared to the time of drug appearance was traced from 1920 to 2000. The curve
      goes down slowly in the time frame of World War II, but rises from 1950 to 1970.
      The elevation could not be suppressed by the appearance of SUs, BGs or improved
      insulin preparations. The curve runs flat from 1980 to 1990, which might be
      related to the use of purified insulin or human insulin therapy. The mortality
      rate of DM indicates that death by hyperglycemic coma and other deaths resulting
      from complications are excluded. The survey of the principal cause of death by DM
      during the period of 1981-1990 indicates that the death rate due to hyperglycemic
      coma is only 1.7% of the total deaths caused by DM. The effect of drug therapy on
      all of the death resulting from DM is not detected. Hospital visitation and
      admission rates of the DM patients have been recorded since 1952 in Japan. This
      curve is rising continuously, and none of the antidiabetic drugs has been able to
      suppress it. These data show that the antidiabetic drugs relieve DM symptoms
      through their effective hypoglycemic actions, but that they cannot suppress the
      mortality rate of DM. It is possible that none of the drugs currently available
      can suppress the increasing tendency of DM patients.

PMID- 14570055
TI  - Glycosylation regulates Notch signalling.
AB  - Intracellular post-translational modifications such as phosphorylation and
      ubiquitylation have been well studied for their roles in regulating diverse
      signalling pathways, but we are only just beginning to understand how
      differential glycosylation is used to regulate intercellular signalling. Recent
      studies make clear that extracellular post-translational modifications, in the
      form of glycosylation, are essential for the Notch signalling pathway, and that
      differences in the extent of glycosylation are a significant mechanism by which
      this pathway is regulated.

PMID- 14570056
TI  - [Historical study of separation technology innovation in the field of
      pharmaceutical science].
AB  - The separation of organic compounds has been carried out using the method of
      distillation and recrystallization since the 17th century.1st separation
      technology innovation (1950s to 1960s). After World War II, the science of
      separating organic compounds evolved to the use of paper or column
      chromatography. 2nd separation technology innovation (1960s to 1980s). In the
      1960s, thin-layer chromatograpy (TLC) was developed. TLC is a convenient
      analytical technique for organic compounds. Separation methods for organic
      compounds using column chromatography and preparative TLC were carried out as
      practical applications. Gas chromatography (GC) was also introduced in the 1960s.
      GC is a useful analytical method for a mixture of various volatile organic
      compounds. Many GC instruments with new kinds of sensors were developed. Gas
      chromatography of nonbenzenoid organometallic compounds and metal complexes was
      successfully conducted by the author. 3rd separation technology innovation (1980s
      to 1990s). In the 1980s, high-performance liquid-chromatography (HPLC) was
      developed. HPLC analytical methods were useful for various kinds of organic
      compounds. In the 1990s, LC-MS and LC-NMR instruments were introduced for
      biomedical products. 4th separation technology innovation (1990s to present).
      Several new ionization methods for mass-spectrometry (electrospray, matrix-aided
      lazer desorption ionization, etc) are applied for proteins and biomedical
      products. Several new separation technologies (supercritical field
      chromatography, capillary electrophoresis, field-flow fractionization, etc.) are
      now being developed.

PMID- 14570057
TI  - Cell-death alternative model organisms: why and which?
AB  - Classical model organisms have helped greatly in our understanding of cell death
      but, at the same time, might have constrained it. The use of other, non-classical
      model organisms from all biological kingdoms could reveal undetected molecular
      pathways and better-defined morphological types of cell death. Here we discuss
      what is known and what might be learned from these alternative model systems.

PMID- 14570058
TI  - Restoring the brain with neural stem cells.

PMID- 14570060
TI  - Abstracts of the 12th International Congress of the European Society for Child
      and Adolescent Psychiatry. September 28-October 1, 2003. Paris, France.

PMID- 14570059
TI  - [Historical and herbological investigation of Yinchenhao].
AB  - The description of "Yinchenhao" in Chinese and Japanese medical and
      pharmaceutical literature, Bencao, was historically examined.Yinchenhao was
      consistently considered an indispensable medicine for treating jaundice. It was
      estimated that in China, a shrubby Artemisia plant just like the Artemisia
      capillaris, or a related plant, was utilized as Yinchenhao in the Liuchao and
      Song dynasties. Further, several kinds of. plants, including Artemisia, were used
      in the Song Dynasty and probably thereafter. Until the Song Dynasty, the leaves
      and stems of elongated aerial parts of the plants described above were used,
      while young (non-elongated) shoots on the stems of the previous year, which were
      called Mianyinchen after the Qing Dynasty, were found to be already utilized in
      the Ming Dynasty. In Japan, the botanical source of Yinchenhao was believed to be
      A. capillaris since the Edo era, without any differentiation in opinion. In the
      early Edo era, the leaves and stems of the plant seem to have been used. But late
      in Edo era, the flower heads of the plant gradually prevailed in the market.

PMID- 14570061
TI  - Chromatin history: our view from the bridge.
AB  - Thirty years ago, our conception of chromatin structure underwent a total
      metamorphosis as the nucleosome era began. In Kurosawa's classic movie 'Rashomon'
      (1951), each participant had a different perspective of the same pivotal event.
      This review outlines our perception of history.

PMID- 14570062
TI  - Abstracts of the 43rd annual meeting of the Society for Psychophysiological
      Research. October 29-November 2, 2003. Chicago, Illinois, USA.

PMID- 14570063
TI  - Can transcription factors function as cell-cell signalling molecules?
AB  - Recent data support the view that transcription factors - in particular,
      homeoproteins - can be transferred from cell to cell and have direct non-cell
      autonomous (and therefore paracrine) activities. This intercellular transfer,
      based on atypical internalization and secretion, has important biotechnological
      consequences. But the real excitement stems from the physiological and
      developmental implications of this mode of signal transduction.

PMID- 14570064
TI  - Capecitabine in colorectal, breast, and other solid tumors: novel therapeutic
      approaches. Selected abstracts from ASCO 2003.

PMID- 14570065
TI  - [Historical study of clinical pharmacy education in Japan (part 1). The founding
      and history of the one-year graduate course of clinical pharmacy practice
      (yakugaku senkouka) at the Meijo University].
AB  - Since there was an increasing demand for highly educated pharmacists with
      clinical experience, a one-year graduate course in clinical pharmacy practice
      (Yakugaku Senkouka) was established at Meijo University in 1975. This was aimed
      to provide pharmacists a training program for clinical skills and hospital
      settings. The course became a leading school in clinical pharmacy education in
      Japan. The present study describes what it was like and how it contributed to the
      development of clinical pharmacy in the country. In this article, the history is
      divided into five terms ranging from 1975 to 2002. The first term (1975-1979): To
      introduce the educational system, a system that was modeled on those in USA was
      introduced. The curriculum of clinical clerkship and the methods for evaluating
      training process were devised. The second term (1980-1984): Clinical clerkships
      were systematized and modified to fit to society. A manual textbook for training
      in clinical pharmacy was edited. The third term (1985-1989): The activities in
      the course were recognized as a new professional practice of pharmacists in Japan
      under The New Medical Law and The Law of Healthcare Insurance. The fourth term
      (1990-1995): Clinical pharmacy became popular nationwide. In Meijo University, a
      new challenge was made to merge clinical pharmacy skills with scientific
      backgrounds. The fifth term (1996-2002): To cope with the trends of extending
      undergraduate pharmacy education to six years, it has been decided that the
      course will be reorganized into a 2-year master's course in clinical pharmacy and
      accepted as a graduate course in 2003. The history of the course, a forerunner of
      clinical pharmacy education in Japan, ended in 2002.

PMID- 14570067
TI  - Free-access era coming to an end at eBMJ.

PMID- 14570066
TI  - [Historical study of clinical pharmacy education in Japan (part 2) retrospective
      evaluation of the roles of the one-year graduate course of clinical pharmacy
      practice (Yakugaku Senkouka) at Meijo University].
AB  - Clinical pharmacy practice education started 30 years ago in Japan. Since 1975, a
      one-year graduate course, clinical pharmacy practice (Yakugaku Senkouka), has
      been offered at Meijo University, making it a leading school to raise pharmacists
      with sufficient experience in hospital settings. This article describes the scope
      of the course, the development of educational systems to meet public demand for
      new pharmaceutical skills, and the influences on reforming the Japanese health
      care system. The content consists of the following: (1) The process of building
      up the first curricula of clerkship, (2) requirements for admission, namely
      including an essay, an interview, school records and an aptitude test, (3)
      establishing the teaching discipline, (4) achievement goals, (5) learning process
      modeled on methods used in the United States, (6) establishing the concept of
      medical ethics, (7) professional status of course graduates, and (8) nationwide
      influence on the social health-care of the country. The one-year graduate course
      of clinical pharmacy practice was terminated in 2002 and is to be reintroduced as
      a two-year graduate school course to cope with the present and future trends in
      health-care systems.

PMID- 14570068
TI  - [A study of the medical treatment for Ho-shun-in, Mrs. Toshiie Maeda, described
      in "Igaku-tensho-ki"].
AB  - The medical commentary "Igaku-tensho-ki," written by Gensaku Manase in the Edo
      era, Japan, describes the medical treatment of Ho-shun-in, Mrs. Toshiie Maeda,
      the first seignior of Kaga. The Igaku-tensho-ki is famous for its clinical
      descriptions of the diseases of many notables such as Emperors and Shoguns by
      their antonyms, and thus is very important for both medical and historical
      studies. Several variant versions are known to exist now. As to the description
      of Ho-shun-in, the details such as the date and place of the treatment, and the
      recipe of the Kampo medicine are not clear. In this study, to clarify these
      things, a comparative study of various descriptions in all of the variants was
      carried out. The results show that the medical treatment was conducted on June
      7th of the lunar calendar, in the 11th year of the Keicho Era (1606) in Edo
      (present-day Tokyo). The disease was thought to be diarrhea caused by the
      infection of bacteria and round worms. Gensaku , effectively prescribed Sho-ko
      en, Kakko-shoki-san with Gorei-san, and Jinryo-byakujutu-san to Ho-shun-in over a
      4-day period. All of these prescriptions were basically based on those in "Manbyo
      kaishun", archaic medical text written in the Ming Dynasty in China, though they
      were derived from different origins.

PMID- 14570069
TI  - [A 50-year history of new drugs in Japan-the development and trends of
      hemostatics and antithrombotic drugs].
AB  - The developments and trends of hemostatic and antithrombotic drugs in Japan were
      investigated chronologically for the last 50 years after the 2nd World War. 1.
      Hemostatic drugs are classified into three groups ; capillary stabilizers, blood
      coagulants and antifibrinolytics. l) As to capillary stabilizers, flavonoid
      (rutin, 1949), adrenochrome derivative (carbazochrome, 1954) and conjugated
      estrogen (Premarin, 1964) were introduced therapeutically. Especially, the
      soluble types of adrenochrome compounds (Adona 1956, S-Adchnon, 1962) were
      devised and used widely in Japan. 2) Drugs concerning blood coagulation,
      thrombin, introduced in 1953, and hemocoagulase, a snake venom introduced in
      1966, were used clinically. V.K. groups producing various coagulation factors
      were introduced as V.K1 (Phytonadione, 1962) and V.K2 (rnenatetrenone,1972), and
      they were admitted in "The Japanese Pharmacopoeia"editions 8 and 14,
      respectively). 3) Regarding antifibrinolytic drugs, Japanese researchers have
      made remarkable contributions. e-Aminocapronic acid (Ipsilon, 1962) and
      tranexamic acid (Transamin, 1965) were developed and used for various abnormal
      bleedings or hemorrhage associated with plasmin over-activation. tranexamic acid
      also proved to suppress inflammations of the throat such as tonsillitis,
      pharyngitis or laryngitis. 2. Antithrombotic drugs are also divided into three
      groups; anticoagulants, antiplatelet drugs and fibrinolytics.1) The
      anticoagulants used therapeutically by injection are heparins (Na-salt, 1951; Ca
      salt, 1962) and low-molecular-weight heparins such as dalteparin (1992),
      parnaparin (1994) and reviparin (1999). The low molecule compounds are superior
      to the original heparins in reducing the risk of bleeding. As oral
      anticoagulants, coumarin derivatives, dicumarol (1950), ethylbiscoumacetate
      (1954), phenylindandione (1956) and warfarin (1962) are known. Warfarin potassium
      is the main drug for oral therapy of thromboembolism lately. Gabexate mesilate
      (1989) and nafamostat mesilate (1989) were developed in Japan and used for DIC
      and acute pancreatitis to inhibit protease enzymes. Argatroban is a unique
      antithrombin product developed by Japanese researchers in 1990, and is used for
      vascular or cerebral thrombosis. After noticing in 1968 that aspirin inhibits
      platelet aggregation and prevents myocardial infraction, projects for developing
      antiplatelet drugs were initiated worldwide. Ticlopidine, originally developed in
      France, was introduced in 1981 and prevailed widely in Japan for reducing the
      risk of thrombotic stroke. Aspirin itself was recognized by the FDA (USA) as an
      antithrombotic drug in 1988, and was also approved by Japanese authorities in
      2000. PGE1 clathrate compounds have also been developed as antiplatelet drugs;
      alprostadil alfadex for injection (1979), and limaprost alfadex for oral use
      (1988). The PGI2 product, beraprost sodium, for oral use followed them in 1992.
      Other antiplatelet drugs with unique mechanisms explored in Japan: Ozagrel
      (1988), which inhibits TXA2 synthetase, cilostazol (1988), which inhibits cAMP
      phosphodiesterase, and sarpogrelate (1993), which blocks 5HT in platelets, are
      the notable drugs in this field. Ethyl icosapentate, from fish oil, is available
      for antiplatelet therapy. Concerning the fibrinolytic system, plasminogen
      activators are useful for thromboembolism. The streptokinase from bacterial
      origin developed in the USA and Europe was not introduced, and urokinase (1965)
      was the first plasminogen activator developed in Japan. Then tissue plasminogen
      activators (t-PA) tisokinase (cell culture, 1991), alteplase (genetical
      recombination, 1991), nateplase (genetical recombination, 1996), monteplase
      (1998) and pamiteplase (1998) were developed and approved for acute myocardial
      infarction. Nasaruplase (prourokinase, cell culture,1991) was also approved for
      the same indication. While the development of the hemostatic drugs ceased in the
      1960s, avid project studies for antithrombotic drugs including fibrinolytics
      began in the 1980s and are progressing now towards new molecular targets. This
      may be due to the increasing tendency of cardiovascular thromboembolic diathesis
      in Japan. (The figures in parentheses are the years approved by the Japanese
      Ministry of Health, Labor and Welfare.)

PMID- 14570070
TI  - [Myrrh and mummy, Kamille and Ka-Mi-Tsu-Re].
AB  - Myrrh and mummy were separately introduced into Japan and were individually
      called MIIRA in Japanese for a certain period of time, during which some
      confusion ensued. Later, it was settled to call them MOTSUYAKU for myrrh and
      MIIRA for mummy. The etymology of related terms is discussed. Camomile (English)
      or Kamille (Dutch) was brought to Japan and named KAMITSURE with the "ts" sound
      inserted. This insertion was the outcome of a popular misunderstanding of the
      phonetic transcription of the Dutch word. The etymology of related terms is also
      discussed.

PMID- 14570071
TI  - [First domestic production of transaminase assay reagents].
AB  - Ultraviolet absorption has continued to improve and has become a commonly used
      method. The development of automated instruments has also contributed to its use,
      making the Reitman-Frankel Method retire from the prominent stage it once
      occupied. While the Camen Method was indicated to be short of substrates, it is
      now used after incorporating improvements proposed from various countries,
      including the JSCC recommendation from Japan, as a titration method for the
      enzyme reference materials. The JSCC Common Standards Method was further
      provisioned through detailed examinations ot its reagents and processes, and is
      utilized under strict conditions. Standardization has thus evolved from more
      technique to what includes reference materials.

PMID- 14570072
TI  - Current readings in nuclear medicine.

PMID- 14570073
TI  - Abstracts of the 2003 NAASO (North American Association for the Study of Obesity)
      annual meeting. October 11-15, 2003. Ft. Lauderdale, Florida, USA.

PMID- 14570074
TI  - Abstracts of CHEST 2003 Scientific Highlights. October 25-30, 2003. Orlando,
      Florida, USA.

PMID- 14570075
TI  - Abstracts of the 54th annual meeting of the American Association for the Study of
      Liver Diseases. October 24-28, 2003. Boston, Massachusetts, USA.

PMID- 14570076
TI  - Prasterone treatment in systemic lupus erythematosus.

PMID- 14570077
TI  - Focus on bioanalysis.

PMID- 14570078
TI  - Effects of situational aggression cues: a quantitative review.
AB  - Meta-analytic procedures were used to assess the degree to which aggression
      related cues present in the environment facilitate aggressive responding among
      negatively aroused subjects. The first study, which examined the so-called
      weapons effect, the effect of name-mediated cues, and other cue effects, showed
      clear evidence that aggression cues augment aggressive responses in negatively
      aroused subjects. This was true for the overall analysis and for name-mediated
      cues, but confirmation of the weapons effect was restricted to cases wherein
      subject sophistication and evaluation apprehension were low. A second study used
      partial correlation analysis to assess independently the effects of seven
      potential mediators of aggression cue effects. Of these, target-based
      facilitation and harm capacity of the aggressive response were found to mediate
      the magnitude of cue-facilitated aggression. A third study showed that these
      mediators augmented cue effects among neutral as well as negatively aroused
      subjects. These outcomes are interpreted as emphasizing the role of cognitive
      factors in the expression of both impulsive and nonimpulsive aggression.

PMID- 14570079
TI  - Adult attachment, working models, and relationship quality in dating couples.

PMID- 14570080
TI  - Biological distribution and significance of brown adipose tissue.
AB  - 1. The structure, location, identification and thermogenic function of brown
      adipose tissue is discussed before describing its distribution in animals. 2.
      With a few interesting exceptions, brown fat occurs almost exclusively in
      mammals. 3. This tissue has been positively identified in thirteen orders, but
      more thorough investigations are required before its absence can be confirmed in
      the remaining eight mammalian orders. 4. Factors influencing the amount and
      activity of brown fat seen between and within species are numerous, but some of
      the most important are body size, diet, environmental temperature, age and
      reproductive state. 5. The role brown fat, and the effects of impairments in its
      function, are described in relation to thermoregulation and the control of energy
      balance and body composition.

PMID- 14570081
TI  - Magnesium: metabolism and hormonal regulation in different species.
AB  - 1. The magnesium ion is of great importance in physiology by its intervention in
      300 enzymatic systems, its membrane role and its function in neuromuscular
      excitability. 2. The skeleton is the first pool of magnesium in the animal body.
      3. For intestinal absorption, renal metabolism, bone accretion and resorption,
      magnesium shows analogies with calcium. 4. Magnesium exchange between
      extracellular, cellular and skeletal compartments are very precisely controlled.
      5. Parathyroid hormone, 1 alpha, 25-dihydroxy-vitamin D3, calcitonin and
      estrogens are the principal hormone systems implicated in magnesium metabolism.
      6. The kidney is the principal site of magnesium excretion and shows important
      magnesium regulation mechanisms.

PMID- 14570082
TI  - [Report from a study tour].

PMID- 14570083
TI  - Chemotherapy, erythropoietin and bloodless surgery in a Jehovah's Witness.

PMID- 14570084
TI  - Introducing the Intergroup 0116 protocol of adjuvant chemo-radiotherapy in
      gastric cancer into clinical practice.
AB  - AIMS: The results of techniques from a well-conducted clinical trial are often
      difficult to reproduce when implemented in community oncology practice. The U.S.
      Intergroup 0116 protocol of adjuvant chemo-radiotherapy in gastric cancer
      presented in mid-2000 produced a survival advantage over surgery alone. The
      current study aims to determine the adherence with protocol design and delivery
      of radiation therapy (radiotherapy) in the initial 20 patients managed with the
      Intergroup 0116 protocol at The National University Hospital, Singapore.
      MATERIALS AND METHODS: A formal quality assurance audit was performed on clinical
      features, radiotherapy treatment charts and simulation films of the first 20
      patients treated with the Intergroup 0116 protocol from July 2000 to September
      2001. Specific details were audited for their consistency with described protocol
      in domains of eligibility criteria, radiotherapy prescription, target volume
      coverage and adherence to dose-limiting normal tissue tolerances. Compliance and
      toxicity with the protocol was assessed by audit of delivered radiotherapy dose,
      treatment interruptions, inpatient admissions and weight loss during
      radiotherapy. RESULTS: The 20 audited patients were appropriately selected on the
      basis of eligibility criteria of Intergroup 0116 protocol. There was only one
      minor variation of radiotherapy target volume coverage resulting from marginal
      coverage of the porta hepatis region. Adherence to the protocol was satisfactory,
      with 19 patients completing the radiotherapy protocol as planned and only one
      major variation in treatment delivery resulting from gastrointestinal toxicity.
      One major and one minor variation in normal tissue-dose constraints occurred on
      the heart and spinal cord, respectively. Compliance with treatment delivery was
      good, with only one patient failing to complete the prescribed radiotherapy dose
      owing to toxicity, although seven patients required treatment interruption.
      CONCLUSION: This audit showed good compliance with radiotherapy design and
      delivery. A formal medical quality assurance audit may provide a useful tool to
      assess complex new protocols introduced into routine departmental practice.

PMID- 14570085
TI  - Variability of the carina-incisor distance as assessed by endoscopic ultrasound.
AB  - AIM: The purpose of this study is to demonstrate variability of the carina
      incisor distance (CID), and define morphological factors associated with this.
      MATERIALS AND METHODS: The carina is clearly visualised on endoscopic ultrasound
      (EUS), and the CID was measured in 50 patients (29 men, 21 women) undergoing EUS
      for various indications (30 oesophageal cancer, 20 other) with Olympus UM-20
      (used in 24 cases) or MH-908 (used in 26 cases) radial echoendoscopes. Patient
      height and weight were compared with CID using Pearson's correlation coefficient.
      RESULTS: Mean CID was 25.7 cm, with a range of 20.5-29 cm (SD +/- 1.99). There
      was no difference between the measured CID in the oesophageal cancer and non
      oesophageal cancer groups, or between the two types of echoendoscope. There was
      highly significant positive correlation between patient height and CID (r =
      +0.750; P < or = 0.01). CONCLUSION: This study demonstrates considerable
      variability of the CID from 20.5-29 cm. It is no longer appropriate to assume a
      'normal' carinal level of 25 cm in all patients. In this study, if the carina was
      accepted to lie at 25 cm, this would have led to radiation therapy missing
      macroscopic disease, a so called 'geographic miss', in nine of the 50 (18%)
      patients. We now routinely record the level of the CID, the upper and lower
      extent of the primary tumour and lymph-node metastases with reference to the
      incisor teeth. This is simple to perform and may assist in radiotherapy planning
      by reducing the geographic miss rate.

PMID- 14570086
TI  - The effect of deep inspiration breath-hold on tumour oxygenation.
AB  - AIM: To investigate the influence of deep inspiration breath-hold on the oxygen
      tension of in-vivo tumours measured using an Eppendorf pO2 histograph. MATERIALS
      AND METHODS: Patients with accessible primary or metastatic tumours > or = 2 cm
      diameter were entered into a protocol measuring tumour oxygenation with an
      Eppendorf pO2 histograph during normal breathing (NB) and deep inspiration breath
      hold (DIBH). Change in oxygen tension was assessed using the Wilcoxon Signed
      Ranks test. RESULTS: Thirty patients were entered in to this protocol. The median
      maximum tumour dimension was 4 cm. The median of the median pO2 of these tumours
      was 18 mmHg. Tumours were assessed during NB and DIBH. Oxygen tension
      measurements along 1-3 pairs of tracks per tumour (median of 2) were obtained.
      The median number of measurements per track was 30 for NB and 29 for DIBH (range
      17-59). In six tumours, the values during NB were significantly higher than
      during DIBH, whereas, for six other tumours, the relationship was the opposite;
      for the remaining 18 patients, no significant difference was observed.
      CONCLUSION: These data show heterogeneity of tumour oxygenation seen with in-situ
      tumours both at baseline and as a result of DIBH. No systematic change in the
      Eppendorf pO2 measurements was seen as a result of DIBH; however, the individual
      tumour responses to DIBH varied dramatically.

PMID- 14570087
TI  - Cumulative interfraction interval analysis of time and fraction size in
      radiotherapy.
AB  - AIMS: Overall treatment time (OTT) and fraction size influence treatment results
      with radiotherapy; yet, being inversely related, it is difficult to distinguish
      their effect independently of each other. This paper proposes a new approach for
      analysing the interrelationship of time and fraction size in terms of cumulative
      interfraction intervals (CIFI) (i.e. intervals between non-successive fractions
      of radiotherapy). MATERIALS AND METHODS: We analysed the influence of CIFI1-6,
      CIFI1-11 and OTTon tumour control by Kaplan-Meier calculation of the primary
      relapse-free survival (PRFS) and Mann Whitney 'U' test in 242 patients with
      epidermoid cancer of the buccal mucosa-gingiva-palate region treated by either
      2.4 Gy/fraction (60 Gy/5 weeks) or 3.5 Gy/fraction (52.5 Gy/3 weeks). RESULTS:
      The results showed that (1) prolongation of CIFI1-11 significantly decreased
      tumour control in the 2.4 Gy but not 3.5 Gy schedule: (2) 3.5 Gy schedule was
      superior to 2.4 Gy schedule, particularly when CIFI1-11 was prolonged (5-year
      PRFS 80.3% vs 30.9%); and (3) OTT did not influence either schedule. CONCLUSIONS:
      Prolonging interfraction intervals (by treatment interruptions, weekend gaps,
      etc.) in the first 2 weeks (when accelerated repopulation attempts are maximal)
      affects treatment results with low fraction sizes but not high fraction sizes;
      OTT probably vicariously reflects the effect of prolonging the intervening CIFI.

PMID- 14570088
TI  - The effect of biological effective dose on time to symptom progression in
      metastatic renal cell carcinoma.
AB  - AIMS: Renal cell carcinoma is commonly thought to be a radioresistant malignancy.
      Retrospective studies report conflicting results on the effect of radiotherapy
      dose escalation on response and time to progression in symptomatic metastatic
      disease; studies using the linear quadratic model have used alpha/beta ratios
      that are inappropriate for slow growing tumours. We aim to describe our
      experience with palliative radiotherapy in this context, relating Biological
      Effective Dose to outcome. MATERIALS AND METHODS: From December 1995 to April
      2001, 143 independent palliative radiotherapy treatments were delivered to 78
      patients in a single institution. Retrospective data was obtained on the
      radiotherapy schedule used, symptom response and time to symptom progression. The
      biological effective dose (BED) was calculated using alpha/beta ratios of 3 and 7
      Gy (BED3 and BED7). The Log-Rank test was used to assess any differences in time
      to progression, and the Cox Proportional Hazards analysis to determine prognostic
      factors of time to progression. RESULTS: Overall symptomatic response rate was
      73%, with most responses being partial (67%). Forty-three (38%) patients had
      symptomatic progression after a median follow-up of 425 days. BED (BED3 or BED7)
      was not significantly different across response types (complete, partial or no
      response; P=0.90 and 0.88, respectively) and was not predictive for time to
      symptomatic progression (P=0.99 for BED3 and P=0.70 for BED7). Patients with bone
      metastases received less total dose (P=0.001), less BED (BED3, P=0.0013, and
      BED7, P=0.0005) and had a significantly longer time to progression than other
      sites of metastases (hazard ratio (HR) 0.4; 95% confidence interval (CI) 0.2-0.7;
      P=0.004). Initial treatment with interferon-alpha alone in patients presenting
      with metastatic disease, before palliative radiotherapy, was also associated with
      a shorter time to symptom progression (HR 4.6; 95% CI 1.5-14.1; P=0.007). On
      removal of these criteria, brain metastases became a significant predictor of
      progression time, with an HR of 2.5 (95% CI 1.0-5.9; P=0.05), showing an
      increased risk of progression with brain metastases compared with metastases
      elsewhere. Time from primary diagnosis to development of metastatic disease was
      not predictive of time to symptom progression (P=0.29). CONCLUSION: Despite the
      widespread assumption that renal cell carcinoma is radioresistant, retrospective
      assessment showed high response rates to palliative radiotherapy. On the basis of
      our data, higher BED does not seem to be a predictor of response or of duration
      of response in the palliative treatment of renal cell carcinoma. Palliation of
      bone pain seems to be particularly durable compared with the palliation of
      symptoms at other sites of metastases. A trend for shorter duration of palliative
      effect of whole-brain radiotherapy was noted.

PMID- 14570089
TI  - Primary or secondary malignancy? Fingerprint evidence.

PMID- 14570090
TI  - Three-dimensional conformal radiotherapy in the radical treatment of non-small
      cell lung cancer.
AB  - Patients with locally advanced, inoperable, non-small cell lung cancer (NSCLC)
      have a poor prognosis mainly due to failure of local control after treatment with
      radical radiotherapy. This overview addresses the role of three-dimensional
      conformal radiotherapy (3D CRT) in trying to improve survival and reduce toxicity
      for patients with NSCLC. Current techniques of 3D CRT are analysed and discussed.
      They include imaging, target volume definition, optimisation of the delivery of
      radiotherapy through improvement of set-up inaccuracy and reduction of organ
      motion, dosimetry and implementation and verification issues; the overview
      concludes with the clinical results of 3D CRT.

PMID- 14570091
TI  - Case selection in the management of cerebral metastases.

PMID- 14570092
TI  - Investigating the palliative efficacy of whole-brain radiotherapy for patients
      with multiple-brain metastases and poor prognostic features.
AB  - AIMS: Trials have shown that patients with multiple-brain metastases and poor
      prognostic features have a short median survival after whole-brain radiotherapy
      (WBRT). Quality of life (QoL) and other parameters to assess the palliative
      efficacy of WBRT have not previously been studied in this group of patients. We
      therefore attempted to do this. MATERIALS AND METHODS: We performed three studies
      between 1997 and 2001. The two later studies were designed according to the
      results from the preceding study. Each of them revealed the difficulties in
      studying this group of unwell patients with a short survival. RESULTS: Thirty
      eight patients were studied. They had at least two of three poor prognostic
      features, such as Karnofsky performance status (KPS) < 70, over 60 years of age,
      and primary other than breast cancer. The overall median survival was 8 weeks
      (95% CI 6-10). Twenty-four patients had a KPS < 70 and a median survival of 6
      weeks (95% CI 4-9). At 8 weeks after WBRT, 14 out of 15 surviving patients for
      whom data were obtained suffered deterioration in QoL scores, Barthel or KPS. Ten
      of the 38 patients (26%, 95% CI 13-43%) improved in at least one of these
      parameters during the assessment period. Only three out of 38 patients
      discontinued steroids after the radiotherapy. Side-effects of WBRT were common.
      All patients experienced alopecia and lethargy after radiotherapy. CONCLUSIONS:
      Further trials involving larger numbers of patients are necessary. These studies
      offer further information on the limited response rates to WBRT, side-effects and
      effects on QoL, which need to be discussed with patients before they accept or
      decline the offer of cranial irradiation.

PMID- 14570093
TI  - Supportive care management of brain metastases: what is known and what we need to
      know. Conference proceedings of the National Cancer Institute of Canada (NCIC)
      Workshop on Symptom Control in Radiation Oncology.
AB  - OBJECTIVES: To review the results of published randomised controlled trials in
      the treatment of brain metastases and, from the knowledge gained from these
      trials, to identify potential study questions. MATERIALS AND METHODS: The
      literature was searched for randomised controlled trials that dealt with the
      management of brain metastases. Potential research questions were identified on
      the basis of the results of the literature review. RESULTS: A number of research
      questions were identified. In the context of the NCIC Symptom Control Group, a
      trial of supportive care alone vs supportive care and whole-brain radiotherapy
      (WBRT) in a subset of patients with the diagnosis of brain metastases was deemed
      to be of highest priority. We discussed a number of issues relating to the
      feasibility of such a trial. CONCLUSIONS: The optimal management of brain
      metastases remains elusive. Despite the results of numerous randomised controlled
      trials, many questions remain unanswered. The magnitude of benefit using WBRT
      above supportive care alone is uncertain. A trial of supportive care alone vs
      supportive care and WBRT may be successful once target population, feasibility
      and methodological issues are thoroughly solved.

PMID- 14570094
TI  - Methylene blue for the treatment and prophylaxis of ifosfamide-induced
      encephalopathy.
AB  - Ifosfamide (IFOS) is used in cancer treatment. Ifosfamide-induced encephalopathy
      (IIE) can result in treatment delay or discontinuation as well as morbidity and
      mortality. Cases using methylene blue (MB) in acute and prophylactic treatments
      are discussed. For acute use, marked central nervous system (CNS) improvement
      occurred within 24h of MB administration. For prophylactic use, the severity of
      the symptoms decreased significantly compared with previous treatment cycles, and
      enabled patients to continue further IFOS therapy. MB has potential use in both
      the acute treatment and prophylaxis of IIE.

PMID- 14570095
TI  - Acute myeloid leukaemia followingg strontium-89.

PMID- 14570096
TI  - The role of chest X-ray and computed tomography thorax in the surveillance of
      testicular tumours.

PMID- 14570097
TI  - Optical aberrations of intraocular lenses measured in vivo and in vitro.
AB  - Corneal and ocular aberrations were measured in a group of eyes before and after
      cataract surgery with spherical intraocular lens (IOL) implantation by use of
      well-tested techniques developed in our laboratory. By subtraction of corneal
      from total aberration maps, we also estimated the optical quality of the
      intraocular lens in vivo. We found that aberrations in pseudophakic eyes are not
      significantly different from aberrations in eyes before cataract surgery or from
      previously reported aberrations in healthy eyes of the same age. However,
      aberrations in pseudophakic eyes are significantly higher than in young eyes. We
      found a slight increase of corneal aberrations after surgery. The aberrations of
      the IOL and the lack of balance of the corneal spherical aberrations by the
      spherical aberrations of the intraocular lens also degraded the optical quality
      in pseudophakic eyes. We also measured the aberrations of the IOL in vitro, using
      an eye cell model, and simulated the aberrations of the IOL on the basis of the
      IOL's physical parameters. We found a good agreement among in vivo, in vitro, and
      simulated measures of spherical aberration: Unlike the spherical aberration of
      the young crystalline lens, which tends to be negative, the spherical aberration
      of the IOL is positive and increases with lens power. Computer simulations and in
      vitro measurements show that tilts and decentrations might be contributors to the
      increased third-order aberrations in vivo in comparison with in vitro
      measurements.

PMID- 14570098
TI  - Action spectrum for photophobia.
AB  - Thresholds for photophobia (light-induced discomfort) were determined at
      wavelengths from 440 to 640 nm for three subjects. Photophobia was assessed by
      means of electromyography, which was used to measure subjects' level of
      squinting. After correction for absorption by macular pigment and the ocular
      media, subjects' functions displayed a trend of increasing sensitivity with
      decreasing wavelength. We propose that the corrected function is indicative of
      increased sensitivity to potential retinal damage by short-wavelength light. It
      is therefore suggested that photophobia serves a function of biological
      protection. Results also suggest that photophobia is significantly mitigated by
      macular pigment in the short wavelengths.

PMID- 14570099
TI  - Optoacoustic diffraction tomography: analysis of algorithms.
AB  - We consider the problem of using the photoacoustic effect to image the optical
      properties of tissue. A region of tissue is assumed to be illuminated by
      frequency-modulated light that creates an ultrasonic wave of the same frequency.
      This wave is detected on a passive array of receiving transducers distributed
      over a circular or a cylindrical aperture. If the frequency is swept over a broad
      band (or, equivalently, if we illuminate with a pulse and Fourier transform the
      response), then a spatial map of a parameter that depends on the optical
      absorption coefficient of the tissue can be recovered. Analytical inversion
      formulas are derived in both two and three dimensions. The effects of band
      limited data on image quality are also investigated.

PMID- 14570100
TI  - Inverse scattering for a three-dimensional object in the time domain.
AB  - An iterative inverse-scattering approach to reconstruction of electrical
      parameter distributions of a three-dimensional object by using time-domain field
      data is presented. The approach is the extension of the forward-backward time
      stepping algorithm previously proposed for a two-dimensional object. Numerical
      examples of simulation data are given to assess the effectiveness of the proposed
      approach.

PMID- 14570101
TI  - Irradiation direction from texture.
AB  - We present a theory of image texture resulting from the shading of corrugated
      (three-dimensional textured) surfaces, Lambertian on the micro scale, in the
      domain of geometrical optics. The derivation applies to isotropic Gaussian random
      surfaces, under collimated illumination, in normal view. The theory predicts the
      structure tensors from either the gradient or the Hessian of the image intensity
      and allows inferences of the direction of irradiation of the surface. Although
      the assumptions appear prima facie rather restrictive, even for surfaces that are
      not at all Gaussian, with the bidirectional reflectance distribution function far
      from Lambertian and vignetting and multiple scattering present, we empirically
      recover the direction of irradiation with an accuracy of a few degrees.

PMID- 14570102
TI  - Topological defects in moire fringes with spiral zone plates.
AB  - We present a study of spatial structures created by superposition of spiral zone
      plates used for generating optical beams with phase singularities. Moire fringes
      are observed that show topological defects similar to those appearing in
      interference patterns of optical vortices. A brief theoretical discussion is
      included that supports the similarities between the two phenomena. Our results
      may lead to interesting applications to digital information processing by optical
      means.

PMID- 14570103
TI  - Radiometrically accurate scene-based nonuniformity correction for array sensors.
AB  - A novel radiometrically accurate scene-based nonuniformity correction (NUC)
      algorithm is described. The technique combines absolute calibration with a
      recently reported algebraic scene-based NUC algorithm. The technique is based on
      the following principle: First, detectors that are along the perimeter of the
      focal-plane array are absolutely calibrated; then the calibration is transported
      to the remaining uncalibrated interior detectors through the application of the
      algebraic scene-based algorithm, which utilizes pairs of image frames exhibiting
      arbitrary global motion. The key advantage of this technique is that it can
      obtain radiometric accuracy during NUC without disrupting camera operation.
      Accurate estimates of the bias nonuniformity can be achieved with relatively few
      frames, which can be fewer than ten frame pairs. Advantages of this technique are
      discussed, and a thorough performance analysis is presented with use of simulated
      and real infrared imagery.

PMID- 14570104
TI  - Moire patterns between aperiodic layers: quantitative analysis and synthesis.
AB  - Moire effects that occur in the superposition of aperiodic layers such as random
      dot screens are known as Glass patterns. Unlike classical moire effects between
      periodic layers, which are periodically repeated throughout the superposition, a
      Glass pattern is concentrated around a certain point in the superposition, and
      farther away from this point it fades out and disappears. I show that Glass
      patterns between aperiodic layers can be analyzed by using an extension of the
      Fourier-based theory that governs the classical moire patterns between periodic
      layers. Surprisingly, even spectral-domain considerations can be extended in a
      natural way to aperiodic cases, with some straightforward adaptations. These new
      results allow us to predict quantitatively the intensity profile of Glass
      patterns; furthermore, they open the way to the synthesis of Glass patterns that
      have any desired shapes and intensity profiles.

PMID- 14570105
TI  - Intrinsic aberrations due to Mie scattering in particle holography.
AB  - Holography of small particles is a newly revived topic because of its importance
      in holographic particle image velocimetry (HPIV). However, the property of
      particle images formed through holography remains largely unexplored. This fact
      undermines the measurement reliability of HPIV techniques and has become one of
      the obstacles in the full deployment of HPIV. We study the intrinsic aberrations
      in the holographic particle image introduced by particle light scattering and
      investigate how accurately holography can deliver information about the particles
      that are being imaged. Consistent with our experimental observations, simulations
      based on Mie scattering theory show that even with a perfect hologram the
      reconstructed particle images demonstrate complex three-dimensional morphologies
      and bodily shifts. These characteristics, manifested as image aberrations, result
      from uneven scattering amplitude and phase distributions across the finite
      aperture of the hologram. Such aberrations degrade the signal-to-noise ratio in
      the reconstructed image as well as introducing systematic errors in detected
      particle image positions. We examine the effect of these aberrations on HPIV
      measurements.

PMID- 14570106
TI  - Effect of spectral correlations on spectral switches in the diffraction of
      partially coherent light.
AB  - The subject is the spectral characteristics of partially coherent light whose
      spectral degree of coherence satisfies or violates the scaling law in diffraction
      by a circular aperture. Three kinds of spectral correlations of the incident
      light are considered. It is shown that no matter whether the partially coherent
      light satisfies or violates the scaling law, a spectral switch defined as a rapid
      transition of spectral shifts is always found in the diffraction field. Different
      spectral correlations of the incident field in the aperture result in different
      points at which the spectral switch occurs. With an increment in the
      correlations, the position at which the spectral switch takes place moves toward
      the point at which the phase of the center frequency component omega0 becomes
      singular for illumination by spatially fully coherent light. For light that
      satisfies the scaling law, the spectral switch is attributed to the diffraction
      induced spectral changes; for partially coherent light that violates the scaling
      law, the spectral switch is attributed to both the diffraction-induced spectral
      changes and the correlation-induced spectral changes.

PMID- 14570107
TI  - Near-field Fourier transform polarimetry by use of a discrete space-variant
      subwavelength grating.
AB  - We present a unique method for real-time polarization measurement by use of a
      discrete space-variant subwavelength grating. The formation of the grating is
      done by discrete orientation of the local subwavelength grooves. The complete
      polarization analysis of the incident beam is determined by spatial Fourier
      transform of the near-field intensity distribution transmitted through the
      discrete subwavelength dielectric grating followed by a subwavelength metal
      polarizer. We discuss a theoretical analysis based on Stokes-Mueller formalism,
      as well as on Jones calculus, and experimentally demonstrate our approach with
      polarization measurements of infrared radiation at a wavelength of 10.6 microm.

PMID- 14570108
TI  - Fundamental limits on isoplanatic correction with multiconjugate adaptive optics.
AB  - We investigate the performance of a general multiconjugate adaptive optics (MCAO)
      system in which signals from multiple reference beacons are used to drive several
      deformable mirrors in the optical beam train. Taking an analytic approach that
      yields a detailed view of the effects of low-order aberration modes defined over
      the metapupil, we show that in the geometrical optics approximation, N deformable
      mirrors conjugated to different ranges can be driven to correct these modes
      through order N with unlimited isoplanatic angle, regardless of the distribution
      of turbulence along the line of sight. We find, however, that the optimal
      deformable mirror shapes are functions of target range, so the best compensation
      for starlight is in general not the correction that minimizes the wave-front
      aberration in a laser guide beacon. This introduces focal anisoplanatism in the
      wave-front measurements that can be overcome only through the use of beacons at
      several ranges. We derive expressions for the number of beacons required to sense
      the aberration to arbitrary order and establish necessary and sufficient
      conditions on their geometry for both natural and laser guide stars. Finally, we
      derive an expression for the residual uncompensated error by mode as a function
      of field angle, target range, and MCAO system geometry.

PMID- 14570109
TI  - Characterization of microstructured optical fibers for wideband dispersion
      compensation.
AB  - Microstructured optical fibers (MOFs) with small hole-to-hole spacing and large
      airholes are designed to compensate the anomalous dispersion and the dispersion
      slope of single-mode fibers. The geometrical parameters that characterize
      triangular MOFs are chosen to optimize the fiber length and the compensation over
      a wide wavelength range. A proper design of the photonic crystal fiber geometry
      allows us to achieve dispersion values of approximately -1700 ps nm(-1) km(-1) at
      1550 nm and to compensate the dispersion of standard fibers within +/- 0.5 ps nm(
      1) km(-1) over a 100-nm range. The MOF dispersion properties have been studied by
      means of a numerical simulator for modal analysis based on the finite-element
      method.

PMID- 14570110
TI  - Photonic crystal waveguide-mode orthogonality conditions and computation of
      intrinsic waveguide losses.
AB  - We simulate the propagation of light in a W1 planar photonic crystal waveguide
      with the three-dimensional finite-difference time-domain method and apply an
      inner product against previously calculated mode profiles to the simulated field
      cross sections. We show that this inner product satisfies mode orthogonality for
      both photonic crystal waveguides and segmented waveguides and use the obtained
      data to evaluate waveguide losses.

PMID- 14570111
TI  - Application of the boundary-element method to the interaction of light with
      single and coupled metallic nanoparticles.
AB  - The boundary-element method is applied to the interaction of light with resonant
      metallic nanoparticles. At a certain wavelength, excitation of a surface plasmon
      takes place, which leads to a resonantly enhanced near-field amplitude and a
      large scattering cross section. The resonance wavelength for different scatterer
      geometries is determined. Alteration of the scattering properties in the presence
      of other metallic nanoparticles is discussed. To treat this problem, a novel
      formulation of the boundary-element method is presented that solves the
      interaction problem for all the coupled particles.

PMID- 14570112
TI  - Azimuthal polarization and partial coherence.
AB  - Partially coherent fields with the electric field parallel to the azimuthal
      coordinate are analyzed by use of the exact angular spectrum representation. The
      known results for fully coherent fields are used to find the permitted forms of
      azimuthally polarized, partially coherent fields. The derived result is then used
      to show that this class of fields is severely restricted because the azimuthal
      polarization state is particularly sensitive to the correlation properties of the
      electric-field components. Two examples of azimuthally polarized fields are
      briefly examined. The first is a class of nondiffracting fields that retain the
      polarization state upon propagation, whereas the second is an example in which
      the azimuthal polarization is broken because the cross-spectral density function
      is not of the permitted form.

PMID- 14570113
TI  - Phase mask for spatial and temporal control of ultrashort light pulses focused by
      lenses.
AB  - The field amplitude associated with ultrashort light pulses was analyzed by using
      the phase-space formalism of the Wigner distribution function (WDF). The
      diffraction integral was properly modified to take into account the dispersion
      effects (up to second order). A two-dimensional WDF associated with a reduced
      pupil function was derived, from which the on-axis irradiance was obtained for
      varying times. A two-dimensional and rotationally symmetric quartic-phase mask to
      control the temporal stretching of femtosecond light pulses passing through
      optical systems was proposed and analyzed. A Gaussian spatial and temporal pulse
      passing through a single lens with and without the phase mask was investigated.

PMID- 14570115
TI  - The Argasidae, Ixodidae and Nuttalliellidae (Acari: Ixodida): a world list of
      valid tick names.
AB  - The world's argasid tick fauna comprises 183 species in four genera, namely
      Argas, Carios, Ornithodoros and Otobius in the family Argasidae. The ixodid tick
      fauna consists of 241 species in the genus Ixodes and 442 species in the genera
      Amblyomma, Anomalohimalaya, Bothriocroton, Cosmiomma, Dermacentor, Haemaphysalis,
      Hyalomma, Margaropus, Nosomma, Rhipicentor and Rhipicephalus in the family
      Ixodidae, with the genus Boophilus becoming a subgenus of the genus
      Rhipicephalus. The family Nuttalliellidae is represented by the monospecific
      genus Nuttalliella. The species names of these ticks, based on seven previous
      complete or partial listings, as well as those of recently described new species,
      are presented in tabular format.

PMID- 14570114
TI  - Adaptations of the tick-borne pathogen, Anaplasma marginale, for survival in
      cattle and ticks.
AB  - The tick-borne cattle pathogen Anaplasma marginale (Rickettsiales:
      Anaplasmataceae) multiplies within membrane-bound inclusions in host cell
      cytoplasm. Many geographic isolates of A. marginale occur that vary in genotype,
      antigenic composition, morphology and infectivity for ticks. A tick cell culture
      system for propagation of A. marginale proved to be a good model for study of
      tick-pathogen interactions. Six major surface proteins (MSPs) identified on A.
      marginale from bovine erythrocytes were conserved on A. marginale derived from
      tick cells. MSP1a and MSP1b were adhesins for bovine erythrocytes, while only
      MSP1a was bound to be an adhesin for tick cells. The tandemly repeated portion of
      MSP1a was found to be necessary and sufficient for adhesion to both tick cells
      and bovine erythrocytes. Infectivity of A. marginale isolates for ticks was
      dependent on the adhesive capacity of the isolate MSP1a, which was found to
      involve both the adhesive properties and sequence of the repeated peptides.
      Cattle immunized with A. marginale derived from bovine erythrocytes or tick cells
      demonstrated a differential antibody response to MSP1a and MSP1b that resulted
      from the differential expression of these proteins in cattle and ticks cells.
      MSP2, derived from a multigene family, was found to undergo antigenic variation
      in cattle and ticks and may contribute to establishment of persistent A.
      marginale infections. MSP1a has been used as a stable genetic marker for
      geographic isolates because the molecular weight varies due to differing numbers
      of the tandem repeats. However, phylogenetic studies of A. marginale isolates
      from North America using MSP1a and MSP4 demonstrated that MSP4 was a good
      biogeographic marker, while MSP1a varied greatly among and within geographic
      areas. Infection and development of A. marginale in cattle and tick cells appears
      to differ and to be mediated by several surface proteins encoded from the small
      genome.

PMID- 14570116
TI  - Phylogeny, evolution and historical zoogeography of ticks: a review of recent
      progress.
AB  - There has been much progress in our understanding of the phylogeny and evolution
      of ticks, particularly hard ticks, in the past 5 years. Indeed, a consensus about
      the phylogeny of the hard ticks has emerged. Our current working hypothesis for
      the phylogeny of ticks is quite different to the working hypothesis of 5 years
      ago. So that the classification reflects our knowledge of ticks, several changes
      to the nomenclature of ticks are imminent. One subfamily, the Hyalomminae, will
      probably be sunk, yet another, the Bothriocrotoninae n. subfamily, will be
      created. Bothriocrotoninae n. subfamily, and Bothriocroton n. genus, are being
      created to house an early-diverging ('basal') lineage of endemic Australian ticks
      that used to be in the genus Aponomma (ticks of reptiles). There has been
      progress in our understanding of the subfamily Rhipicephalinae. The genus
      Rhipicephalus is almost certainly paraphyletic with respect to the genus
      Boophilus. Thus, the genus Boophilus will probably become a subgenus of
      Rhipicephalus. This change to the nomenclature, unlike other options, will keep
      the name Boophilus in common usage. Rhipicephalus (Boophilus) microplus may still
      called B. microplus, and Rhipicephalus (Boophilus) annulatus may still be called
      B. annulatus, but the nomenclature will have been changed to reflect our
      knowledge of the phylogeny and evolution of these ticks. New insights into the
      historical zoogeography of ticks will also be presented.

PMID- 14570117
TI  - The use of the nuclear protein-encoding gene, RNA polymerase II, for tick
      molecular systematics.
AB  - Phylogenetic studies of ticks have been increasing in recent years, particularly
      in the use of molecular data. However, all of the studies to date are either
      limited to the mitochondrial genome or to a few nuclear ribosomal genes. There is
      a need to explore the use of nuclear protein-encoding genes because these genes
      direct most aspects of the phenotypic traits in the development of an organism.
      We report here the test of a nuclear protein-encoding gene, RNA polymerase II,
      for the phylogenetic study of ticks. Thirty-eight ticks representing 26 species
      of hard and soft ticks were chosen for the study. The pairwise divergences among
      sampled species are ranged from 0.3 to 15.2% and most of the substitutions are
      transitions. In addition, the nucleotide composition is not obviously biased in
      POL II gene. The trees inferred from the POL II sequences using maximum parsimony
      (MP), neighbor joining (NJ), and maximum likelihood (ML) by PAUP* and MrBayes are
      largely concordant with the existing phylogenies. Our study demonstrated that POL
      II gene sequences contain strong phylogenetic signals in ticks at the generic and
      higher levels. POL II has proven to be a useful gene for resolving tick
      phylogeny.

PMID- 14570118
TI  - A proteomics approach to characterizing tick salivary secretions.
AB  - The saliva of ticks contains a complex mixture of bioactive molecules including
      proteins that modulate host responses ensuring successful feeding. The limited
      amount of saliva that can be obtained from ticks has hampered characterization of
      salivary proteins using traditional protein chemistry. Recent improvements in two
      dimensional gel electrophoresis, mass spectrometry, and bioinformatics provide
      new tools to characterize small amounts of protein. These methods were employed
      to characterize salivary proteins from Amblyomma americanum and Amblyvomma
      maculatum. Salivation was induced by injection of dopamine and theophylline. It
      was necessary to desalt and concentrate saliva before analysis by 2-D
      electrophoresis. Comparison of 1-D and 2-D gel patterns revealed that the major
      protein component of saliva did not appear on 2-D gels. Characterization of this
      protein showed that it was identical to the major protein present in the
      hemolymph of both tick species. Protein profiles obtained by 1-D and 2-D gel
      electrophoresis were similar for both tick species, however, higher
      concentrations of lower molecular weight proteins were present in A. maculatum.
      Protein analysis by MALDI-TOF mass spectrometry and western blot analysis showed
      that except for the most abundant protein with a molecular weight of 95 kDa, all
      of the proteins detected were of host origin. It is not known if this is an
      artifact of the collection method or has physiological significance. In either
      case, in these species of ticks, host proteins will have to be removed from
      saliva samples prior to 2-D analysis in order to characterize lower abundance
      proteins of tick origin.

PMID- 14570119
TI  - RNA interference: applicability in tick research.
AB  - The rapid development of new genetic tools has boosted the gene discovery
      machinery. RNA interference (RNAi), a gene silencing process, has been recently
      used in several eukaryotic organisms to elucidate the function(s) of unknown
      genes and biochemical pathways. We used the dsRNA technique in Amlyomma
      americanum female ticks to test the applicability of the RNAi approach in ticks.
      Incubation of tick salivary glands (TSGs) in vitro and in vivo injection into
      whole female ticks with histamine binding protein (HBP) dsRNA led to a reduction
      in the HBP transcripts in the dsRNA treated groups. The dsRNA-injected ticks had
      a profound difference in their feeding pattern compared to control ticks that
      might reflect an increase in local histamine concentrations at the feeding sites.
      To our knowledge, this is the first RNAi study in ticks. In conclusion, RNAi can
      be applied in ticks and might be used to test the function of key proteins
      crucial for avoiding host defense at the tick-host interface.

PMID- 14570120
TI  - An inhibitor of thrombin-stimulated blood platelet aggregation from the salivary
      glands of the hard tick Amblyomma variegatum (Acari: Ixodidae).
AB  - The tropical bont tick, Amblyomma variegatum can cause intense skin irritation
      and inflammation and bites that often develop into septic wounds or abscess in
      their host. Crude salivary gland extract (SGE) of partially engorged A.
      variegatum females as well as SGE protein fractions purified by three-step
      reverse phase HPLC procedure were tested for their anti-aggregatory effect on
      isolated human blood platelets stimulated with thrombin and compared with the
      effect of recombinant hirudin. At concentrations 10(-3) and 5 x 10(-3) microg
      protein/ml the following rank order of antiplatelet activity was detected: AV
      16/3 (inhibitor purified from AV-III, third purification) > SGE > AV-II (fraction
      from first purification) > AV-III (fraction from first purification) > hirudin.
      The effect of all fractions tested was dose-dependent. For fraction AV 16/3, the
      inhibitory effect was 49 and 61% for 10(-3) and 5 x 10(-3) microg protein/ml,
      respectively. The results suggest that protein fractions from A. variegatum SGE
      possess an antithrombin effect on human blood platelets with hirudin-like
      activity.

PMID- 14570121
TI  - A preliminary linkage map of the tick, Ixodes scapularis.
AB  - A linkage map of the Ixodes scapularis genome was constructed based upon
      segregation amongst 127 loci. These included 84 random amplified polymorphic DNA
      (RAPD) markers, 32 Sequence-Tagged RAPD (STAR) markers, 5 cDNAs, and 5
      microsatellites in 232 F1 intercross progeny from a single, field-collected P1
      female. A preliminary linkage map of 616 cM was generated across 14 linkage
      groups with one marker every 10.8 cM. Assuming a genome size of approximately
      10(9) bp, the relationship of physical to genetic distance is approximately 300
      kb/cM in the I. scapularis genome.

PMID- 14570122
TI  - Expression of defensin-like peptides in tick hemolymph and midgut in response to
      challenge with Borrelia burgdorferi, Escherichia coli and Bacillus subtilis.
AB  - Challenge of Dermacentor variabilis by hemocoel injection with Borrelia
      burgdorferi but not Bacillus subtilis or Escherichia coli provoked secretion of
      two low molecular weight peptides into the hemolymph plasma; the lower band co
      migrated with a band previously identified as varisin (a tick defensin). These
      findings are consistent with reports that D. variabilis controls B. burgdorferi
      but not B. subtilis or E. coli by defensin-dependent bacteriolysis. Challenge of
      the tick midgut by capillary artificial feeding with bacteria also provoked
      expression of multiple low molecular weight peptides. In this case, however, all
      three bacteria elicited the response. Two bands, including the defensin-like
      peptide were expressed following challenge with B. subtilis and E. coli, but only
      the upper band following challenge with B. burgdorferi. Although they appeared
      intact, these spirochetes were no longer viable suggesting that borreliae in the
      midgut are controlled by a different method than the lytic response of the D.
      variabilis hemolymph. DD-RT-PCR revealed multiple mRNAs in the midgut of D.
      variabilis following challenge with B. burgdorferi, E. coli and Rickettsia
      montana. Although their identification remains to be determined, the large number
      of genes expressed in response to bacterial challenge presents intriguing
      possibilities for explaining the ability of the tick midgut to destroy invading
      microbes at the cellular level.

PMID- 14570123
TI  - Involvement of antibacterial peptide defensin in tick midgut defense.
AB  - Animals are constantly threatened by pathogenic microorganisms and have developed
      cellular and humoral immune responses to combat these infections. Invertebrates
      possess only an innate non-specific immune response. Antimicrobial substances are
      major components of innate immunity not only in invertebrates but also in
      vertebrates. Despite the importance of ticks as vectors of disease very little is
      known about their immune system. Our recent studies have revealed that four
      defensin isoforms are present in Ornithodoros moubata. These four isoforms are
      constitutively expressed in the midgut and up-regulated in response to blood
      feeding. Moreover, a mature peptide of defensin isoform A has been isolated from
      the tick midgut lumen. These findings indicate Ornithodoros defensins are
      involved in tick midgut defense against potentially harmful invasive microbes.

PMID- 14570124
TI  - Dynamic changes in Lyme disease spirochetes during transmission by nymphal ticks.
AB  - Ticks are not crawling needles, merely delivering infectious agents to vertebrate
      hosts. A sophisticated interplay takes place between ticks, pathogens, and
      vertebrate hosts. The relationship between Ixodes ticks and the Lyme disease
      spirochetes they transmit involves subtle changes in spirochete populations that
      maximize their chances of being transmitted. An understanding of this complex
      interplay will, hopefully, allow the development of new tools to block
      transmission of tick-borne agents.

PMID- 14570125
TI  - Preliminary observations on specific adaptations of exophilic ixodid ticks to
      forests or open country habitats.
AB  - Some features of three-host exophilic ticks important for their survival differ
      at the generic level in relation to the types of their habitat. Ixodes and
      Haemaphysalis are typical forest genera. Hyalomma is an open country genus,
      whereas Dermacentor and Rhipicephalus, having some features of forest ticks, are
      closer to the ticks of open country. Forest ticks encounter rather stable and
      favorable temperature, humidity and illumination conditions as compared with open
      country ticks. A few differences determining every-day survival, hostseeking. and
      reproduction of ticks are considered. (1) Tolerance to desiccation is very low in
      forest ticks and much greater in ticks of open country. (2) Lack of eyes in
      forest ticks (having, however, epithelial photoreceptor cells) and formation of
      eyes as special morphological structures in ticks of open country. (3) Capability
      of mating and insemination of unfed specimens both on and off hosts in forest
      ticks (Ixodes) and insemination of partially engorged females only on hosts by
      fed males in open country ticks. (4) Reciprocal sexual dimorphism where in forest
      ticks females have a larger body than males and in open country ticks this
      correlation is opposite. (5) Linear dependence between female weight and number
      of eggs laid is established in forest ticks after the female weight becomes
      higher than 50% of mean engorgement weight whereas in open country ticks linear
      dependence begins to reveal itself much earlier. (6) In forest ticks the
      compensatory growth occurs only during adult feeding whereas in open country
      ticks such a growth occurs both during nymphal and adult feeding. The adaptive
      nature of the above differences and their evolutionary trends have been
      hypothesized.

PMID- 14570126
TI  - How specific are host-produced kairomones to host-seeking ixodid ticks?
AB  - Ixodid ticks respond to host-produced substances (kairomones) that influence the
      ticks' host-finding behavior. In the laboratory adult blacklegged ticks, Ixodes
      scapularis Say, lone star ticks, Amblyomma americanum L., and American dog ticks,
      Dermacentor variabilis (Say) became akinetic on residues rubbed from their
      principal hosts (deer for the former two species and dogs for the latter).
      However, arrestment also occurred when adults of these species were tested using
      the same method bioassay, but with host substances reversed (i.e., I. scapularis
      and A. americanum against canine substances, and D. variabilis against deer gland
      substances). Although adult D. variabilis exhibited arrestant responses to deer
      substances and are often found along trails used by deer, they apparently make
      little use of deer as hosts. It is unclear whether responding to deer-produced
      kairomones may have disadvantages for D. variabilis. Until the active components
      of host-produced arrestment kairomones are isolated, identified and evaluated in
      behavioral tests, this host-finding strategy remains only partially understood.

PMID- 14570127
TI  - Photoperiodic control of developmental diapause in nymphs of prostriate ixodid
      ticks (Acari: Ixodidae).
AB  - Extrinsic control of developmental diapause in nymphs of prostriate ticks of the
      subgenus Ixodes sensu stricto (Ixodes ricinus and Ixodes persulcatus from Eurasia
      and Ixodes scapularis from North America) appears to be based on a complex two
      step photoperiodic reaction of a short-day/long-day type. Diapause control in the
      subgenus Afrixodes (the South African tick Ixodes rubicundus) appears to be based
      on a simple long-day reaction. The option between non-diapause development and
      diapausing arrest in engorged nymphs is determined by both pre- and post-feeding
      photoperiodic regimes. Consequently diapausing arrest in engorged nymphs of
      Ixodes sensu stricto can be induced either by a short-day (after their
      engorgement) or by a long-day regime (in unfed nymphs), while active, non
      diapause development is possible only when the short-day pre-feeding regime is
      followed by a long-day post-feeding regime. The photoperiodic response in I.
      (Afrixodes) rubicundus nymphs seems to be of the long-day type both before and
      after feeding. Consequently this non-diapause development is enabled by a long
      day regime, while diapause is induced by a short-day regime of exposure.
      Nevertheless, there are some indications that the control of nymphal diapause in
      the latter species is also of a complex nature.

PMID- 14570128
TI  - Detection and identification of spotted fever group rickettsiae in ticks
      collected in southern Croatia.
AB  - A total of 197 ticks belonging to four species (Haemaphysalis punctata, Hyalomma
      marginatum, Rhipicephalus bursa and Dermacentor marginatus) collected in October
      2000 from domestic animals in southern Croatia were examined for the presence of
      rickettsiae by molecular techniques. Specific sequences of the rickettsiae were
      detected in 25 (12.7%) of ticks tested. The prevalence of infection in D.
      marginatus and H. marginatum ticks was 36.8 and 64.7%, respectively. None of the
      ticks belonging to the species H. punctata or Rh. bursa were infected. Sequence
      analysis of amplified products revealed that D. marginatus ticks are infected
      with Rickettsia slovaca, whereas H. marginatum are infected with R.
      aeschlimannii. The results of this study extend the knowledge of the geographic
      distribution of SFG rickettsiae and indicate that at least two of them, with yet
      uncertain pathogenicity to humans, are present in ticks in southern Croatia.

PMID- 14570129
TI  - Immunogenicity of Ehrlichia ruminantium grown in tick cell lines.
AB  - Ehrlichia (previously Cowdria) ruminantium, the pathogen which causes heart-water
      in domestic and wild ruminants, can now be propagated in cell lines from one
      vector (Amblyomma variegatum) and five non-vector (Ixodes scapularis, I. ricinus,
      Boophilus decoloratus, B. microplus and Rhipicephalus appendiculatus) tick
      species. E. ruminantium isolates from West and South Africa and the Caribbean
      vary in their cell line preference, growth patterns and immunogenic capability.
      In laboratory trials, certain combinations of tick cell line and E. ruminantium
      isolate were highly immunogenic in sheep. These trial vaccines were grown under
      specific in vitro conditions and administered as a single intravenous dose of
      freshly harvested whole, live culture. Following immunisation and subsequent
      exposure to virulent E. ruminantium, protected sheep showed no clinical response
      and a range of serological responses.

PMID- 14570130
TI  - Kinetics of experimental infection of sheep with Ehrlichia ruminantium cultivated
      in tick and mammalian cell lines.
AB  - Inoculation of sheep with Ehrlichia (previously Cowdria) ruminantium which has
      been cultivated in mammalian endothelial cell cultures is almost always followed
      by a severe clinical reaction, whereas inoculation of the agent cultivated in
      tick cell lines usually does not provoke a clinical response, but may result in
      seroconversion and/or protection against subsequent challenge with virulent
      stabilates. A quantitative, real-time PCR assay was developed to determine the
      kinetics of infection (rickettsaemia) in sheep inoculated with tick cell- and
      mammalian cell-derived E. ruminantium (Gardel isolate). The method and initial
      results are described, and the significance of the findings is discussed in
      relation to the clinical responses of the sheep.

PMID- 14570131
TI  - A review of studies on the transmission of Anaplasma phagocytophilum from sheep:
      implications for the force of infection in endemic cycles.
AB  - We review the findings of a longitudinal study of transmission of the
      intracellular tick-borne bacterium Anaplasma phagocytophilum from sheep to Ixodes
      ricinus ticks under natural conditions of tick attachment in the UK. In this
      study, sheep-to-tick transmission efficiency varied in a quadratic relationship
      with the number of adult ticks that were feeding on the sheep. We raise the
      hypothesis that this relationship may be due to conflicting effects of the
      density of ticks on bacterial survival and target cell (neutrophil) fluxes at the
      tick-host interface: in the same sheep at the same time, resistance to ticks was
      progressively inhibited with increasing number of feeding adult ticks, and
      investigation of serological responses to tick antigens suggesting loss of
      resistance may be associated with polarisation of host Th1 to Th2 type responses
      to ticks. We also raise the hypothesis that these properties, with superimposed
      effects on tick survival, may mean that variation in tick density is an important
      causal factor of observed variations in the force of A. phagocytophilum infection
      amongst different geographic foci.

PMID- 14570132
TI  - Sodium valproate facilitates the propagation of granulocytic ehrlichiae
      (Anaplasma phagocytophilum) in HL-60 cells.
AB  - As already shown, some inducers of the differentiation of promyelocytic cells
      along the granulocytic pathway, such as dimethylsulphoxide (DMSO) or all-trans
      retinoic acid, can enhance propagation of granulocytic ehrlichiae in HL-60 cell
      cultures. This study was conducted to prove whether sodium valproate, a salt of
      di-n-propylacetic acid (VPA) known to trigger cellular differentiation in several
      solid and hematopoietic malignancies is similarly efficient in ehrlichial
      cultures. Two cell lines derived from HL-60, that is, low-passage
      undifferentiated HL-60 (HL-60F) and high-passage HL-60 spontaneously
      differentiated towards monocytic phenotype (HL-60J) were grown in RPMI 1640
      medium supplemented with 10% FBS. The respective HL-60F and HL-60J IC50-values
      for NaVPA were estimated to be 0.8 and 2.2 mM under these culture conditions; to
      stimulate the differentiation, the respective doses of 0.3 and 1.2 mM were then
      applied. When the NaVPA-treated cells of both lines were challenged with an
      ehrlichial laboratory strain (HGE), maintained in splenectomized NMRI mice, the
      respective 1-2 and < or = 0.1% primary infection rates in HL-60F and HL-60J
      cultures were observed 3 days post-inoculation. In comparison, only rare (< or =
      0.1%) infected HL-60F and no infected HL-60J cells were recorded under the same
      experimental conditions in untreated control cultures. HGE continuously
      propagated in NaVPA-supplemented HL-60F cultures remained infectious to mice at
      least up to the 95th passage (12 months). NaVPA can thus facilitated continuous
      propagation of granulocytic ehrlichiae in cell cultures without a substantial
      loss of infectiveness.

PMID- 14570133
TI  - Reduced weight gain due to subclinical Anaplasma phagocytophilum (formerly
      Ehrlichia phagocytophila) infection.
AB  - Tick-borne fever (TBF) is caused by the rickettsia Anaplasma phagocytophilum
      (formerly Ehrlichia phagocytophila) and is a common disease in sheep in areas of
      Norway infested by Ixodes ricinus ticks. TBF can cause both direct and indirect
      losses to sheep kept on tick-infested pastures. In the present work we studied a
      sheep flock of 26 ewes and 50 lambs on pasture from May until September. No cases
      of TBF had earlier been observed on this pasture. Blood samples from lambs with a
      reduced weekly weight gain were collected and analysed for A. phagocytophilum
      infection by blood smear examination. In addition, at the end of the study, sera
      from all lambs were analysed by an indirect fluorescent antibody assay (IFA) to
      determine the antibody titre to E. equi. No clinical signs of tick-borne
      infections were observed, except in one lamb. However, 30 (60%) of the lambs
      grazing on this pasture became infected with A. phagocytophilum, and the infected
      lambs had a reduced weight gain (mean) of 3.8 kg compared with the uninfected
      lambs. The present study indicates that A. phagocytophilum infection may be
      widespread and contribute to considerable productivity losses even on pastures
      with no apparent tick infestation.

PMID- 14570134
TI  - Ticks and tick-borne diseases of livestock belonging to resource-poor farmers in
      the eastern Free State of South Africa.
AB  - The paper provides a summary of three studies conducted in the eastern Free State
      of South Africa between 1998 and 2000. In a questionnaire-based study
      approximately 21% of interviewed resource-poor farmers (n = 150) indicated that
      they experienced problems with ticks and tick-borne diseases. About 56% of
      farmers indicated that tick-related problems were most severe in summer, while
      32% indicated that the most problems were encountered in winter. About 12%
      indicated that the tick problems were experienced throughout the year. Farmers
      also indicated that the highest tick burdens were experienced between spring and
      early winter. The principal ticks infesting cattle (n = 30) were found to be
      Boophilus decoloratus (53.1%). Rhipicephalus evertsi evertsi (44.7%),
      Rhipicephalus follis (1.0%), Rhipicephalus gertrudae (0.7%) and Rhipicephalus
      warburtoni (0.4%). On small stock (n = 188), R. evertsi evertsi (68%) and B.
      decoloratus (32%) were recorded as the main ticks in the study area. A sero
      epidemiological survey of cattle (n = 386) showed that 94% of cattle were
      seropositive for Babesia bigentina by IFAT, while 87% were sero-positive for
      Anaplasma by indirect ELISA. All the animals were sero-negative for Babesia bovis
      and this is probably because the tick vector, Boophilus microplus, is not present
      in the study area. All sheep and goats were sero-positive for Theileria species
      by IFAT while 85% of sheep and 100% of goats tested positive for Anaplasma
      species by competition inhibition ELISA. The high incidence of positive
      serological results for B. bigemina and Anaplasma in cattle, and Theileria and
      Anaplasma in sheep and goats and the absence of clinical cases would indicate
      that this area is endemically stable for these diseases.

PMID- 14570135
TI  - Tick-host-Borrelia population interactions: long-term records in Eastern Europe.
AB  - During 10 spring and summer seasons (1992-2001), the dynamics of the epizootic
      process in natural foci were studied in taiga forests of the Pre-Ural region,
      Russia. In these foci, Borrelia garinii, Borrelia afzelii and tick-borne
      encephalitis (TBE) virus circulate transmitted by their main vector tick, Ixodes
      persulcatus. Main parameters of the epizootic process were calculated for each
      season. In three seasons (1993, 1996, and 1999) all parameters characterizing the
      abundance of unfed nymphs and adult ticks, as well as the prevalence of Borrelia
      and TBE virus in them, increased sharply and simultaneously. These seasons were
      preceded by years of population peaks in forest rodents (1992, 1995, and 1998),
      especially Clethrionomys glareolus voles, the dominant species in the local
      mammalian fauna. Apparently, the possibility of horizontal transmission of the
      agents of tick-borne infections sharply increases in such years and this results
      in the intensification of their dissemination.

PMID- 14570136
TI  - Remotely sensed correlates of phylogeny: tick-borne flaviviruses.
AB  - Vector-borne pathogen systems are limited by climate, principally through its
      impact on the distribution, abundance and population dynamics of the vectors and
      on the interaction of vectors with their hosts. This leads to the prediction that
      climate has been a significant factor in the evolution of these pathogens and, by
      implication, will be important in future events on both evolutionary and
      ecological time-scales. New phylogenetic trees of organisms, that describe their
      evolutionary history, are routinely available, but explanations for the driving
      force and constraints that have shaped the evolutionary origin of new pathogen
      strains are rare. Under the force of environmental pressures that change in space
      and time, which pathogens are likely to emerge in new places and where will this
      be? To answer such questions, data from molecular biology can be linked with data
      from satellites that allow us to characterize environmental conditions on a
      global scale. Broad-scale patterns in the satellite imagery are consistent with
      the pattern of new tick-borne flaviviruses having evolved sequentially in a cline
      across the world. So far, the distribution of three tick-borne flaviviruses from
      western Europe have been captured simultaneously by the same 10 satellite-derived
      seasonal climatic variables. Once this procedure is extended to the remaining
      viruses in this clade, we shall test for significant matches between their
      phylogenetic tree and an independent tree derived from quantitative descriptions
      of the viruses' 'eco-space'. This will indicate the extent of key ecological
      drivers for specific evolutionary events, whose biological basis can then be
      explored in detail.

PMID- 14570137
TI  - Understanding the relationships between landscape connectivity and abundance of
      Ixodes ricinus ticks.
AB  - The density of Ixodes ricinus ticks in a heterogeneous landscape of northern
      Spain was determined and associated with some aspects of habitat topology. The
      habitat mosaic was used to quantify connectivity between patches of different
      tick density. The analysis revealed that patches with high tick abundance are
      'stepping-stone' territories that, when removed from the landscape, cause large
      changes in connectivity. Sites with medium tick abundance do not cause such a
      critical transition in connectivity. Patches with low tick abundance, but optimal
      abiotic conditions for survival are located within the minimum cost corridors
      network joining the patches, while those sites where the tick has been
      intermittently collected are located at variable distances from this network.
      These results suggest that tick distribution in a zone is highly affected not
      only by abiotic variables (vegetation and weather) but also by host movements.
      Whether these high-density 'stepping-stone' patches occur in other tick species
      needs to be evaluated because of the potential implications of these foci for
      human health.

PMID- 14570138
TI  - Analysis of weather effects on variability in Lyme disease incidence in the
      northeastern United States.
AB  - In this study, variability in reported Lyme disease incidence between 1993 and
      2001 was analyzed in seven states in the northeastern part of the USA. Positive
      significant correlations at p < 0.05 were found in all states between early
      summer disease incidence and the June moisture index in the region two years
      prior. These correlations may reflect an enhanced nymphal Ixodes scapularis
      survival under wetter conditions. In some states, significant correlations were
      observed related to warmer winter weather a year and a half prior to disease
      incidence, which may have been due to higher survival and activity levels of the
      white-footed mouse, an important host for I. scapularis ticks.

PMID- 14570139
TI  - Molecular and biochemical diagnosis of esterase-mediated pyrethroid resistance in
      a Mexican strain of Boophilus microplus (Acari: Ixodidae).
AB  - We examined pyrethroid resistant Mexican strains of Boophilus microplus using
      biochemical and molecular tests to determine the mechanisms conferring
      resistance. Permethrin hydrolysis assays and esterase activity gels indicated
      enhanced esterase-mediated metabolic detoxification in the Cz strain, while one
      other pyrethroid resistant strain, SF, and two pyrethroid susceptible strains had
      lower levels of permethrin hydrolysis. Results from assays using a PCR-based test
      to detect a pyrethroid target site resistance-associated mutation in the tick
      sodium channel gene found only low levels of mutations in the Cz strain, while
      the SF strain had a high level of the mutated sodium channel alleles. A specific
      esterase, designated CzEst9, believed to be responsible for the esterase-mediated
      pyrethroid resistance in the Cz strain was purified, and the gene encoding CzEst9
      cloned.

PMID- 14570140
TI  - In vitro detection of acaricide resistance in Boophilus microplus (Acari:
      Ixodidae).
AB  - The cattle tick Boophilus microplus causes significant economic losses in cattle
      in the tropical areas of Central and South America. Acaricides are widely used to
      control tick infestations, with the consequent selection of tolerant and
      resistant subpopulations. Detoxifying enzymes, and esterases in particular, have
      been associated with organophosphate resistance in Mexican isolates of B.
      microplus ticks. Here, we present results of the biochemical detection of
      esterases and oxidases in 20 isolates of larvae and adult ticks and the effect of
      esterase and oxidase inhibitors on larvae and adult stages of the tick. Our
      results indicate the presence of significant differences both in vivo and in
      vitro between esterase and oxidase activities of OP-susceptible and OP-resistant
      isolates, even when samples were collected in the same area. The importance of
      such differences in regionalized integrated pest management and in the US Tick
      Eradication Program is discussed.

PMID- 14570141
TI  - Progress towards the eradication of Amblyomma variegatum from the Caribbean.
AB  - Progress in the Caribbean Amblyomma Program (CAP) is reviewed since its inception
      in 1995 when regional eradication activities for Amblyomma variegatum ticks were
      initiated using Bayticol pour-on. Technical achievements in the various islands
      were slow initially, and showed a wide diversity in attaining eradication
      targets. St. Kitts, considered as a model program. eliminated the tropical Bont
      tick (TBT) from most of the island in less than 3 years. However, the elimination
      of very low numbers of residual adult TBT that persisted in three 'hot-spots'
      took another 3 years. A similar problem was faced in St. Lucia, although the
      approach there was to cull the wild cattle in the last remaining hot-spot. Both
      islands were certified as 'Provisionally free from TBT' in November 2001. In
      2002, Anguilla and Montserrat attained the same status, and Barbados and Dominica
      also qualify for certification. Certification is based on strict, three-monthly,
      surveillance criteria: essentially, two successive TBT-free surveillance rounds
      on a statistically acceptable sample of the livestock population. Within the
      responsibility of the CAP, three islands remain TBT-infested, Antigua, Nevis, and
      St. Martin/St. Maarten. Nevis is of concern because it has been operational since
      late 1995, and appears unable to resolve the problem of treating stray small
      ruminants. Current funding should be adequate to complete eradication on Nevis
      and in St. Martin/St. Maarten. The major outstanding challenge is Antigua. In
      comparison to other islands they have the largest number of livestock, and have
      much larger populations than originally reported: sheep and goats are 4-5-fold
      higher, and cattle are 1.35-fold higher. The cost for Bayticol is, therefore,
      almost double and an additional US dollars 1.5 million is required for that
      commodity alone.

PMID- 14570142
TI  - The susceptibility of different species and stages of ticks to entomopathogenic
      fungi.
AB  - Boophilus annulatus, Hyalomma excavatum and Rhipicephalus sanguineus ticks were
      shown to be susceptible to different entomopathogenic fungi under laboratory
      conditions. Comparative results of bioassays using five different fungal species
      showed that some strains of Metarhizium anisopliae are highly pathogenic against
      various tick stages tested. In contrast to to their activity against insects,
      fungi also affected tick eggs. All tested tick stages including those feeding on
      a host were found to be susceptible to these fungi, except for adult H.
      excalatimn ticks, which were relatively resistant.

PMID- 14570143
TI  - Control of Ixodes scapularis and Amblyomma americanum through use of the '4
      poster' treatment device on deer in Maryland.
AB  - Deer self-treatment devices ('4-posters') were evaluated for their efficacy in
      reducing populations of blacklegged ticks, Ixodes scapularis, and lone star
      ticks, Amblyomma americanum. At each of three locations in Maryland, 25 '4
      posters' were operated in study areas of approximately 5.18 km2. Populations of
      host-seeking ticks were monitored by flagging of treated areas and similar
      untreated control areas without '4-posters.' From 1998 to 2002 the percent
      mortalities achieved were 69, 75.8 and 80 at the three study sites infested with
      I. scapularis nymphs, and 99.5 and 95.3 for A. americanum nymphs at the two sites
      where this species occurred.

PMID- 14570144
TI  - The use of a 4% (w/w) deltamethrin collar (Scalibor ProtectorBand) in the
      extended control of ticks on dogs.
AB  - Deltamethrin (4%, w/w) formulated in a polymer matrix system (Scalibor
      ProtectorBand, Intervet International BV) was evaluated for the prevention of
      ticks on dogs. Controlled laboratory trials were conducted, wherein dogs wearing
      anti-tick collars were compared with control dogs and artificially infested by
      adult Ixodes ricinus and/or Rhipicephalus sanguineus ticks. The activity of the
      collars increased from 24 to 48 h post-treatment (pt) wherein tick numbers were
      reduced to 78.7% for I. ricinus and to 77% for R. sanguineus. The proportion of
      ticks controlled after the second infestation on D7 pt increased to 99% for I.
      ricinus and 99.5% for R. sanguineus. For I. ricinus adult ticks, an efficacy of
      95.4% was reached over a period of 5.5 months and approximated 90% for R.
      sanguineus. Hence, the efficacy of the deltamethrin-impregnated dog collar was
      >90% for 6 months against both tick species. There was no significant difference
      between the efficacy of the collar against either R. sanguineus or I. ricinus. A
      subsequent field study wherein 82 dogs were wearing the collar and monitored for
      tick infestation indicated that the duration of efficacy was between 5 and 6
      months.

PMID- 14570145
TI  - Adolescent erythrocytes: influence of high density lipoproteins-cholesterol (HDL
      c) plasmatic levels on Na+/Li+ exchange kinetics.
AB  - An inverse relationship between HDL-c plasmatic levels and Li+ flux (Na+-Li+
      exchange mediated) has been reported in normotensive individuals with
      hypertensive ancestors as well as in essential hypertensive subjects. This
      lipoprotein reaction with plasmatic membrane components induces modifications in
      membrane transport mechanisms as well as in cellular enzymes. In this paper we
      present data on Li+ flux (Na+-Li+ exchange mediated) in red blood cells from
      normotensive individuals without hypertensive ancestors. Kinetic analysis of Li+
      efflux as a function of Na+(extracell) concentration was carried out. Vmax and Km
      values were determined. HDL-c plasmatic levels were also determined. Vmax showed
      a significant inverse correlation with HDL-c levels. No significant correlation
      of Km values with HDL-c levels was observed. The data presented support previous
      data showing that variable Vmax is sensitive to cellular environmental factors.
      Otherwise the Km variable not influenced by these factors is sensitive to
      hereditary influences.

PMID- 14570146
TI  - The effect of swimming exercise on lipid peroxidation in the rat brain, liver and
      heart.
AB  - We intended to study the effect of swimming exercise on the brain, liver and
      heart malondialdehyde (MDA) levels which are the last product of oxidation, and
      to compare them with the brain, liver and heart MDA levels of controls. The
      experiments were carried out on 20 Wistar rats which were fed with a standard
      laboratory chow diet ad libitum. Rats were distributed in two groups, control
      group (n = 10) and exercise group (n = 10). The exercise group rats were exposed
      to swimming exercise for 30 minutes. After this animals in each group were
      sacrificed by decapitation, their brain, liver and heart tissues were quickly
      removed. MDA levels of the brain, liver and heart were determined according to
      the method in which MDA reacts with thiobarbituric acid. Results were evaluated
      by the Mann-Whitney U test. The liver and heart MDA levels in the exercise group
      were (29.59+/-6.73 and 10.49+/-1.90 nmol/g tissue, respectively) significantly
      higher than in the control group (21.78+/-3.46 and 8.86+/-1.25 nmol/g tissue,
      p<0.01 and p<0.05, respectively). However, the brain MDA levels were similar in
      both groups (exercise group 19.37+/-5.50 nmol/g tissue and control group 16.58+/
      2.44 nmol/g tissue; p=0.325). It is concluded that swimming exercise might cause
      oxidative stress.

PMID- 14570147
TI  - Modified treadmill protocol for evaluation of physical fitness in pediatric age
      group--comparison with Bruce and Balke protocols.
AB  - The aim of this study was to compare classical Balke and Bruce protocols with our
      modification of Balke protocol in pediatric cardiorespiratory diagnostics. The
      modification of Balke consists of nine stages per 1 min at a constant velocity of
      5.6 km x h(-1) and increasing elevation from 6% to 22% in 2% increments. Sixty
      healthy children (mean age = 13.3+/-0.2 years; BMI = 18.8+/-0.6 kg x m(-2); mean
      +/- 95% CI), divided into three groups of 20 children each, matched by age,
      height and BMI performed integrative cardiopulmonary exercise testing using one
      of the treadmill protocols mentioned. At the end of each exercise increment and
      throughout the recovery period the children were asked to rate the perceived
      exertion (RPE) using the Borg Category Ratio scale--CR-10. Exercise results
      showed that Balke protocol had the longest duration (21.7+/-0.6 min.) and the
      lowest values for VO2/kg (34.2+/-1.8 ml x min(-1) x kg(-1)) due to the minimal
      workload increments. Bruce protocol had intermediate duration (14.9+/-1.1 min.)
      and children achieved the highest VO2/kg (48.6+/-2.7 ml x min(-1) x kg(-1)) but
      the test is symptom-limited which is ethically unacceptable in childhood.
      Exercise data revealed that our modification of the classical Balke protocol had
      an optimal duration (11 min.) and yielded peak VO2/kg values (39.4+/-2.3 ml x
      min(-1) x kg(-1)) adequate for evaluation of children's exercise capacity.
      Children's ratings of perceived exertion were highest in Bruce protocol (6.5+/
      0.4) and lowest in the original Balke protocol (4.5+/-0.8). In conclusion, the
      modification of Balke protocol is suitable and reliable for screening and
      clinical testing in pediatric age group.

PMID- 14570148
TI  - Corrections of prooxidant-antioxidant homeostasis of organism under hypoxia of
      different genesis by yackton, a new pharmacological preparation.
AB  - The aim of the present work was to study the antioxidant activity of the new
      derivative of succinic acid-succinate mono[(2-dimethyl-amino) ethyl ether] of
      succinic acid (yackton) under conditions of hypoxic and hemic hypoxia as well as
      to examine in vitro the antiradical activity of this preparation. Hypoxia in the
      rats was modelled by: (i) allowing the rats to breath a gas mixture with 7% O2
      and 93% N2 for 30 minutes (hypoxic hypoxia), and (ii) injecting the rats sodium
      nitrite subcutaneously in a dose of 60 mg/kg body weight (hemic hypoxia). Yackton
      was injected intraperitoneally to both groups 30 minutes before the extreme
      influence in a dose of 140 mg/kg body weight. Then in homogenates and in post
      mitochondrial fractions of liver, heart, lungs, brain we studied the content of
      secondary products of lipid peroxidation (LPO), activity of antioxidant enzymes
      superoxide dismutase (SOD) and catalase, and the activity of enzymes responsible
      for the maintenance of reduced glutathione (GSH) glutathione reductase (GR-ase)
      and glutathione peroxidase (GP-ase). In vitro studies were made on the
      antiradical activity of yackton in reaction with the stable radical
      diphenylpicrylhydrazine (DPPH) as well as on the reaction velocity of the
      preparation with DPPH, and its period of semi-transformation in a non-radical
      form. It was shown that yackton treatment before hypoxic and hemic hypoxia
      decreased lipid peroxidation (LPO) level and increased SOD activity. After the
      yackton injection the state of glutathione system was normalized in comparison
      with its state at hypoxic and hemic hypoxia. Yackton had no antiradical
      properties in vitro. We concluded that yackton promotes optimization of
      prooxidant-antioxidant homeostasis of the organism under the hemic and hypoxic
      hypoxia acting as antioxidant of a non-direct action.

PMID- 14570149
TI  - Exercise performance and oxygen uptake efficiency slope in obese children
      performing standardized exercise.
AB  - Oxygen uptake efficiency slope (OUES) is an index meant to provide an objective
      measure of cardiopulmonary function at submaximal exercise. The aim was to study
      the exercise performance and OUES in obese children performing standardized
      exercise. Sixty children aged 6-17 years performed incremental treadmill exercise
      test. They were divided into two groups matched by age, sex and height: thirty
      obese subjects (15 girls/15 boys; BMI = 27.4+/-1.7 m x kg(-2)) and 30 controls
      (BMI = 18.8+/-1.0 m x kg(-2)). Perceived exertion was assessed by means of CR-10
      Borg scale. The duration of the exercise for the obese children was significantly
      shorter than for controls (p = 0.010) but obese children had greater absolute
      values for oxygen uptake (VO2 peak mL x min(-1) = 1907+/-249 vs. 1495+/-208; p =
      0.013) which, adjusted for body mass, decreased significantly (VO2/kg mL x min(
      1) x kg(-1) = 29.2+/-1.4 vs. 33.6+/-1.3; p < 0.001). OUES correlated strongly
      with VO2 peak (r = 0.91) and oxygen pulse (r = 0.80), as well as with
      anthropometric variables height (r = 0.88) and age (r = 0.83). Extremely high
      correlation was found between OUES calculated for 100% of exercise duration and
      OUES at the anaerobic threshold (r = 0.979; p < 0.001). No significant
      differences were found between the studied groups concerning the absolute values
      of OUES. Obese children rated perceived exertion significantly higher than
      controls (Borg score 6.2+/-0.4 vs. 5.2+/-0.4; p = 0.001). In conclusion, the
      absolute metabolic cost of exercise and perceived exertion were higher in the
      obesity group. OUES is an objective measure of cardiopulmonary reserve that
      doesn't require a maximal effort but it is considerably dependent on
      anthropometric variables which impedes its interpretation as exercise index in
      childhood.

PMID- 14570150
TI  - The effects of peptide and nonpeptide antagonists of angiotensin II receptors on
      the noradrenaline uptake of different brain structures in rats with angiotensin
      II-induced increase of water intake.
AB  - Angiotensin II (ANG II) significantly increased noradrenaline (NA) uptake by
      cortical, hypothalamic and hippocampal synaptosomes thus activating noradrenergic
      neurotransmission. ANG II did not affect NA uptake by striatal synaptosomes. The
      interaction between AT1 receptors and noradrenergic neurons and the involvement
      of brain noradrenergic neurotransmitter system in ANG II-induced drinking in rats
      is suggested by the increase of NA uptake in hypothalamus and frontal cortex
      which are rich in AT1 receptors and are of importance for drinking behavior. The
      ANG II-receptor antagonists losartan, EXP 3174, sarmesin and saralasin decreased
      NA uptake in all brain regions studied as compared to the uptake in the same
      brain regions of ANG II-injected animals thus antagonising the effect of ANG II.
      There is no relationship between the inhibition of ANG II-induced water intake
      and the changes of NA uptake under the effect of the ANG II-receptor antagonists.

PMID- 14570151
TI  - Hematological alterations in the Otsuka Long-Evans Tokushima fatty (OLETF) rats-
      a model of type 2 diabetes mellitus.
AB  - The OLETF rat develops microangiopathic complications similar to human diabetes
      and is considered a useful model of Type 2 DM. Erythrocyte, platelet and
      leucocyte abnormalities described in diabetic patients are thought to play a role
      in the development of diabetic microangiopathy. This study was designed to
      investigate whether OLETF rats show hematological alterations and the effect of
      sucrose treatment on metabolic and blood parameters. Hematological parameters,
      body weight, food and water intake, fasting and non-fasting blood glucose (BG)
      and HbA1c were measured in OLETF rats treated for two months with 30% sucrose
      added to drinking water. Non-treated OLETF rats and non-diabetic Long-Evans
      Tokushima Otsuka (LETO) rats were used as controls. In the control OLETF rats the
      number of platelets (Plt) and red blood cells (RBC) was higher, while the mean
      cell volume (MCV) and the mean cell hemoglobin content (MCH) were lower compared
      with LETO. Mean cell hemoglobin concentration (MCHC) was significantly higher in
      the diabetic rats. Sucrose administration decreased food intake and body weight
      and increased fasting blood glucose and HbA1c. It resulted in a decrease of RBC,
      Hb, Hct, MCV and MCH compared with control OLETF, while Plt count increased
      significantly. Our results point to significant alterations in erythrocyte count
      and morphology and Plt count in diabetic OLETF rats compared with non-diabetic
      LETO. Sucrose administration accelerated the development of diabetes, affected
      blood cells inducing the suppression of RBC and an increase in Plt count and some
      of its effects persisted after sucrose withdrawal.

PMID- 14570152
TI  - Aging and synaptic changes in the paraventricular hypothalamic nucleus of the
      rat.
AB  - The age-related differences in the synapses of the paraventricular hypothalamic
      nucleus (PVN) were studied with transmission electron microscopy in young (3
      month-old) and senescent (25-month-old) Wistar rats. The changes in the
      axodendritic (ADS) and axospinous (ASS) synapses in the PVN neuropil were
      determined by morphometry. The majority of synapses were of the ADS type. In
      senescent rats the density of both ADS and ASS was diminished. The mean area of
      the ASS presynaptic boutons in aged rats was more enlarged than of the boutons in
      the ADS. The parameters characterising synaptic vesicles (SV) were diminished in
      aging rats. The number of SV per synaptic bouton decline was not significantly
      different. The changes in the length of synaptic contact zone (SCZ) were not
      significant with the exception of the total SCZ length per 1000 microm2 and the
      total area of the SCZ per 1000 microm3 in the ADS. The decrease of the number of
      dendritic spines (DS) per 1000 microm2 in the neuropil was significantly age
      related diminished. Moreover, the mean area of the DS was significantly enlarged.

PMID- 14570153
TI  - Cholecystokinin and learning and memory processes.
AB  - Cholecystokinin (CCK) is a classical brain-gut peptide that exerts a variety of
      physiological actions in the gastrointestinal tract and central nervous system.
      CCK occurs in several molecular forms of varying aminoacid length, the sulphated
      octapeptide (CCK-8) being the predominant form in the brain. CCK mediates its
      effects through interaction with specific receptors subdivided in two subtypes-
      CCK-A (present in the periphery and in few selected brain nuclei) and CCK-B (the
      predominant receptor subtype in the brain). CCK is implicated in variety of
      behavioral functions as satiety, anxiety, exploratory and locomotor activity and
      learning and memory. After a brief description of the distribution, molecular
      forms, release, inactivation, etc. of CCK in the brain, the present review
      summarizes the recent data on the role of CCK in learning and memory. The memory
      enhancing effects of CCK have been demonstrated in various types of memory. Data
      showing that CCK-A receptors mediate mnemonic while CCK-B receptors mediate
      amnestic effects are also presented.

PMID- 14570154
TI  - About the biological effects of high and extremely high frequency electromagnetic
      fields.
AB  - This paper deals with the effects of high (microwave) and extremely high
      (millimetre waves, MMW) frequency electromagnetic fields on the membrane
      processes and ion channels, molecular complexes, excitable and other structures.
      Microwaves as well as millimetre waves are widely used in medical practice and in
      everyday life. The existence of interaction between the exogenous and endogenous
      electromagnetic fields with biological systems is now a subject of intense
      discussion. The most contentious question is the existence of a possible specific
      (non-thermal) effect of microwaves, unrelated to that caused by increased
      temperature. Although numerous data have been published on the possible non
      thermal effects of the studied electromagnetic fields on different kinds of
      living systems, only little understanding is gained about the modes of microwave
      action. Here we review data, which provide evidence that non-thermal microwave
      effects do exist and may play a significant role. This evidence is based on
      research at all biological levels, from cell-free systems through cells, tissues
      and organs, to animal and human organisms.

PMID- 14570155
TI  - Sulfated polysaccharides of brown seaweed Cystoseira canariensis bind to serum
      myostatin protein.
AB  - Natural sulfated polysaccharides (SPs) derived from brown seaweed comprise a
      complex group of macromolecules with a wide range of important physiological
      properties. SPs have been shown to bind and directly regulate the bioactivity of
      growth factors and cytokines such as basic fibroblast growth factor, interferon,
      various enzymes and transforming growth factor. Myostatin is a member of the
      transforming growth factor-beta (TGF-beta) family that acts as a negative
      regulator of skeletal muscle mass. In this work we demonstrated that SPs isolated
      from the brown seaweed Cystoseira canariensis bind to the myostatin protein in
      serum.

PMID- 14570156
TI  - Seeing right through you: applications of optical imaging to the study of the
      human brain.
AB  - A new set of techniques allows for the study of brain function by near-infrared
      light, exploiting two optical phenomena: Changes in light absorption are
      determined by changes in the concentration of substances like oxy- and
      deoxyhemoglobin, and changes in light scattering occur as a consequence of
      variations of properties of membranes and corpuscles in the neural tissue.
      Methods based on light absorption can be used to study hemodynamic changes in the
      brain, whereas those based on light scattering can be used to study neuronal
      activity and to provide anatomical information at a cellular and subcellular
      level. Three optical imaging approaches can be used to study living tissue:
      reflection, optical coherence tomography (OCT), and photon migration. These three
      approaches vary in their penetration (from less than a millimeter for reflection
      to up to 3-5 cm for photon migration) and spatial resolution (from a micron level
      for reflection and OCT to a millimeter and centimeter level for photon
      migration). This issue includes a collection of articles reviewing applications
      of these technologies to the study of brain and other bodily functions in humans.

PMID- 14570157
TI  - Activation of the prefrontal cortex to trauma-related stimuli measured by near
      infrared spectroscopy in posttraumatic stress disorder due to terrorism.
AB  - To develop a noninvasive method for psychophysiological assessment of
      posttraumatic stress disorder (PTSD), 34 victims of the Tokyo Subway Sarin Attack
      in 1995 including 8 diagnosed as PTSD and 12 controls were examined by a
      multichannel near-infrared spectroscopy (NIRS) system. Hemodynamic response in
      the prefrontal cortex was monitored during the presentation of trauma-related and
      control stimuli by video images. Skin conductance response (SCR) was also
      examined. Oxygenated hemoglobin significantly increased during the trauma-related
      image in the victims with or without PTSD. Deoxygenated hemoglobin significantly
      decreased only in victims with PTSD. No significant alteration was found in
      controls. Significantly enhanced SCR was also observed in the victims with PTSD
      during trauma-related stimuli. The findings suggest that measurement of cerebral
      hemodynamic response by NIRS is useful for psychophysiological assessment of
      PTSD.

PMID- 14570158
TI  - Advances in optical imaging of the newborn infant brain.
AB  - New methods of imaging the oxygenation, hemodynamics, and metabolism of the
      newborn infant brain are being developed, based on illumination of the head with
      near-infrared light. Techniques known as optical topography and optical
      tomography have the potential to provide valuable information about the function
      of the normal brain, and about a variety of cerebral pathology such as hypoxic
      ischemia. Optical methods provide a unique means of monitoring brain oxygenation
      safely in an intensive care environment without interference with the normal
      handling of the infant. Studies on infants have focused on the assessment of
      steady-state regional cerebral perfusion and tissue oxygenation, as well as
      monitoring hemodynamic changes in response to sensory stimulation. Recent
      technological and methodological advances in this research field are reviewed,
      and the likely impact of optical imaging methods on the care of newborn infants
      is assessed.

PMID- 14570159
TI  - Functional near-infrared optical imaging: utility and limitations in human brain
      mapping.
AB  - Although near-infrared spectroscopy (NIRS) was developed as a tool for clinical
      monitoring of tissue oxygenation, it also has potential for neuroimaging. A wide
      range of different NIRS instruments have been developed, and instruments for
      continuous intensity measurements with fixed spacing [continuous wave (CW)-type
      instruments], which are most readily available commercially, allow us to see
      dynamic changes in regional cerebral blood flow in real time. However,
      quantification, which is necessary for imaging of brain functions, is impossible
      with these CW-type instruments. Over the past 20 years, many different approaches
      to quantification have been tried, and several multichannel time-resolved and
      frequency-domain instruments are now in common use for imaging. Although there
      are still many problems with this technique, such as incomplete knowledge of how
      light propagates through the head, NIRS will not only open a window on brain
      physiology for subjects who have rarely been examined until now, but also provide
      a new direction for functional mapping studies.

PMID- 14570160
TI  - Fast cerebral functional signal in the 100-ms range detected in the visual cortex
      by frequency-domain near-infrared spectrophotometry.
AB  - Brain activity is associated with physiological changes, which alter the optical
      properties of the tissue in the near-infrared part of the spectrum. Two major
      types of optical signals following functional brain activation can be
      distinguished: a slow signal due to hemodynamic changes and a fast signal, which
      is directly related to neuronal activity. The fast signal is small and therefore
      difficult to detect. We used a specially noise-optimized frequency-domain near
      infrared spectrometer with a pi-sensor, which was expected to be particularly
      sensitive to deeper tissue layers, to investigate the human visual cortex during
      visual stimulation generated by a checkerboard. We were able to detect
      significant fast signals in single light bundles, but not in pi-signals. The fast
      signals were mostly collocated with strong slow hemodynamic signals, but showed a
      higher degree of localization than the latter. The latencies of 40 +/- 16 ms of
      the fast signals were similar between locations. Our results also indicate that
      the brain responds differently to a single and double (forth and back) reversal
      of the checkerboard, with a stronger reaction upon the double reversal.

PMID- 14570161
TI  - Optical coherence tomography: technology and applications for neuroimaging.
AB  - Optical coherence tomography (OCT) is an emerging imaging technology with
      applications in biology, medicine, and materials investigations. Attractive
      features include high cellular-level resolution, real-time acquisition rates, and
      spectroscopic feature extraction in a compact noninvasive instrument. OCT can
      perform "optical biopsies" of tissue, producing images approaching the resolution
      of histology without having to resect and histologically process tissue specimens
      for characterization and diagnosis. This article will review several of the
      current technological developments in OCT. To illustrate the potential of this
      technology for neuroimaging, applications for imaging neural development, the
      neural retina, tumors of the central nervous system, and the microsurgical repair
      of peripheral nerves will be presented. This technology offers a potential
      investigative tool for addressing many of the present challenges in neuroimaging.

PMID- 14570162
TI  - Optimum filtering for EROS measurements.
AB  - The event-related optical signal (EROS) is a relatively new technology that
      provides noninvasive data about the time course of neural activity in
      circumscribed cortical areas. However, much still remains to be learned about the
      physiology and physics underlying the observed signals. We examined the
      instrumental and physiological noise observed in the intensity modulation and
      phase-delay measurements produced by a frequency domain oxymeter in response to
      steady-state auditory stimuli. We present here data on the effects of different
      filters on the between-subjects response consistency for amplitude and phase
      measurements. The results of these analyses may help explain some apparently
      discrepant results previously reported from different laboratories (Steinbrink et
      al., 2000), and illustrate differences between data from different types of
      measurements.

PMID- 14570164
TI  - The event-related optical signal (EROS) in visual cortex: replicability,
      consistency, localization, and resolution.
AB  - We previously reported a fast and localized noninvasive event-related optical
      signal (EROS) elicited by visual field quadrant stimulation in occipital brain
      areas (Gratton, Corballis, Cho, Fabiani, & Hood, 1995). We now present a
      replication and extension of that experiment. In addition, we propose a new
      method for estimating the cross-validity of the results based on intersubject
      correlations, report further data on the localization of EROS, and present an
      analysis of its spatial resolution. The results replicate our original findings.
      The intersubject correlation is generally quite high (r = .6-.8). The spatial
      resolution analysis indicates that activities from cortical areas located
      approximately 1.5 cm apart are measurable independently without cross talk. This
      study provides further support for the idea that noninvasive optical imaging can
      be used to derive images of brain activity combining good spatial and temporal
      resolution.

PMID- 14570163
TI  - Hemodynamic evoked response of the sensorimotor cortex measured noninvasively
      with near-infrared optical imaging.
AB  - We have performed a noninvasive bilateral optical imaging study of the
      hemodynamic evoked response to unilateral finger opposition task, finger tactile,
      and electrical median nerve stimulation in the human sensorimotor cortex. This
      optical study shows the hemoglobin-evoked response to voluntary and nonvoluntary
      stimuli. We performed measurements on 10 healthy volunteers using block paradigms
      for motor, sensory, and electrical stimulations of the right and left hands
      separately. We analyzed the spatial/temporal features and the amplitude of the
      optical signal induced by cerebral activation during these three paradigms. We
      consistently found an increase (decrease) in the cerebral concentration of oxy
      hemoglobin (deoxy-hemoglobin) at the cortical side contralateral to the
      stimulated side. We observed an optical response to activation that was larger in
      size and amplitude during voluntary motor task compared to the other two
      stimulations. The ipsilateral response was consistently smaller than the
      contralateral response, and even reversed (i.e., a decrease in oxy-hemoglobin,
      and an increase in deoxy-hemoglobin) in the case of the electrical stimulation.
      We observed a systemic contribution to the optical signal from the increase in
      the heart rate increase during stimulation, and we made a first attempt to
      subtract it from the evoked hemoglobin signal. Our findings based on optical
      imaging are in agreement with results in the literature obtained with positron
      emission tomography and functional magnetic resonance imaging.

PMID- 14570165
TI  - The mind's eye, looking inward? In search of executive control in internal
      attention shifting.
AB  - In studies of mental counting, participants are faster to increment a count that
      was just incremented (no-switch trial) than to increment a different count
      (switch trial). Investigators have attributed the effect to a shift in the
      internal focus of attention on switch trials. Here we report evidence for other
      bottom-up and top-down contributions. Two stimuli were mapped to each of two
      counts. The no-switch facilitation was greater when stimuli repeated than when
      they were different. Event-related potential (ERP) activity associated with
      repetitions was anterior to that associated with switching. Runs of no-switch
      trials elicited faster responses and frontal ERP activity. Runs of switches and
      large counts both elicited slow responses and reduced P300 amplitudes. Bottom-up
      processes may include priming on no-switch trials and conflict on switch trials.
      Top-down processes may control conflict, subvocal rehearsal, and the contents of
      working memory.

PMID- 14570166
TI  - A generally robust approach to hypothesis testing in independent and correlated
      groups designs.
AB  - Standard least squares analysis of variance methods suffer from poor power under
      arbitrarily small departures from normality and fail to control the probability
      of a Type I error when standard assumptions are violated. These problems are
      vastly reduced when using a robust measure of location; incorporating bootstrap
      methods can result in additional benefits. This paper illustrates the use of
      trimmed means with an approximate degrees of freedom heteroskedastic statistic
      for independent and correlated groups designs in order to achieve robustness to
      the biasing effects of nonnormality and variance heterogeneity. As well, we
      indicate when a boostrap methodology can be effectively employed to provide
      improved Type I error control. We also illustrate, with examples from the
      psychophysiological literature, the use of a new computer program to obtain
      numerical results for these solutions.

PMID- 14570167
TI  - Locus of the effect of temporal preparation: evidence from the lateralized
      readiness potential.
AB  - It is well established that reaction time (RT) is shorter when a response signal
      is preceded by a warning signal, because the warning signal causes the
      participant to prepare for the upcoming response. A review of chronometric and
      psychophysiological studies reveals the prevailing view that this temporal
      preparation operates mainly at a motor level speeding up rather late processes.
      To assess the locus of this preparation effect, we conducted two experiments
      employing the lateralized readiness potential (LRP). Contrary to this prevailing
      view, the results of both experiments clearly indicate that temporal preparation
      enhances the processing speed of relatively early processes, because a
      manipulation of temporal uncertainty affected RT, the P300 latency, and the
      stimulus-to-LRP interval but not the LRP-to-keypress interval.

PMID- 14570168
TI  - Circadian rhythm and desensitization in chemosensory event-related potentials in
      response to odorous and painful stimuli.
AB  - Olfactory (H2S) and trigeminal (CO2) event-related potentials (ERPs) were studied
      with respect to circadian rhythm and desensitization. ERPs, perceived odor and
      pain intensity, oral temperature, blood pressure, heart rate, nasal volume, and
      sleepiness were assessed four times at 04:00, 08:00, 12:00, 16:00, 20:00, and
      24:00 hr in five young men. For each of these 24 sessions per participant, H2S
      and CO2 were each presented in 15 series of five stimuli with a 5-s ISI within
      and 30-s ISI between series. ERP amplitudes, but not latencies, followed a
      circadian rhythm (largest at 16:00 and smallest at 04:00) similar to oral
      temperature and opposite to sleepiness. Amplitudes decreased (most pronounced at
      16:00 and 20:00) and latencies increased with repeated stimulation, suggesting
      desensitization, in accordance with odor and pain intensity. These findings imply
      that circadian rhythm and desensitization should be considered in chemosensory
      ERP studies.

PMID- 14570169
TI  - Reliability of smooth pursuit, fixation, and saccadic eye movements.
AB  - The present study investigated the reliability and susceptibility to practice
      effects of oculomotor tasks. Smooth pursuit, fixation, antisaccade, and
      prosaccade tasks were administered to 31 healthy participants to assess internal
      consistency (Cronbach's alpha) and within-session practice effects. Twenty-one of
      these participants were retested after an average interval of 57.86 days to
      assess temporal stability and between-session practice effects. Internal
      consistencies were high for most measures, with few within-session performance
      changes. Test-retest reliabilities of most measures were good. Between-session
      practice effects were most consistently observed on the antisaccade task,
      indicated by reduced error rate and improved spatial accuracy at retest.
      Magnitude of improvement on these measures was related to performance, indicating
      that poor performers benefited most from repeated assessment. These findings
      support the trait nature of oculomotor function and point to the need to take
      into consideration between-session practice effects on the antisaccade task in
      longitudinal studies.

PMID- 14570170
TI  - Electrophysiological evidence of visual encoding deficits in a cross-modal
      attentional blink paradigm.
AB  - Two experiments are reported in which two target stimuli, T1 and T2, were
      presented at variable stimulus onset asynchronies (SOAs). In Experiment 1, T1 and
      T2 were visual stimuli embedded in a rapid serial visual presentation (RSVP)
      stream of distractors. Participants were asked to report T1 and T2 at the end of
      the stream. In Experiment 2, T1 was an auditory stimulus, and T2 a visual
      stimulus embedded in an RSVP stream. Participants made a speeded discriminative
      response to T1, and reported T2 at the end of the stream. An attentional blink
      (AB) effect was observed in both experiments: T2 report suffered at short SOA
      compared to long SOA. During the AB, the amplitude of the P300 component of the
      event-related potential (ERP) locked to T2 onset was sensibly reduced in both
      experiments. Behavioral and ERP results were very similar across the two
      experiments. Implications for models of the AB effect are discussed.

PMID- 14570171
TI  - Influence of phonological expectations during a phoneme deletion task: evidence
      from event-related brain potentials.
AB  - Several studies have identified a negativity [the phonological mismatch
      negativity (PMN)] preceding the N400 during auditory sentence comprehension. The
      present study investigated whether the PMN reflects a prelexical or lexical stage
      of spoken word recognition. Event-related brain potentials (ERPs) were recorded
      to investigate phonological processing independently from lexical/semantic
      influences during a task requiring metalinguistic analysis of speech stimuli.
      Participants were instructed to omit the initial phoneme from a word ("clap"
      without the/k/) after which they heard a correct (lap) or incorrect (cap, ap,
      nose) answer. The PMN (peaking at 270 ms) was largest to incorrect items and did
      not differentiate between items that shared the same rime and items that were
      phonologically unrelated to the correct choice. Further, the PMN did not differ
      between word (cap) and nonword (ap) choices. The P300 was largest to correct
      items but was also seen to choices that rhymed with the correct answer. It is
      concluded that the PMN serves as a neural marker for the analysis of acoustic
      input merging with prelexical phonemic expectations.

PMID- 14570172
TI  - Autonomic recovery and habituation in social anxiety.
AB  - Growing evidence suggests that, contrary to expectation, high trait socially
      anxious (HTSA) and low trait socially anxious (LTSA) individuals show comparable
      autonomic reactivity during stressful speech tasks. To test the hypothesis that
      autonomic differences between groups might emerge during recovery or habituation,
      35 HTSA and LTSA participants gave two impromptu speeches. Measures of anxiety
      experience as well as cardiovascular, electrodermal, respiratory, and vagal
      activation were obtained. Despite greater reports of anxiety experience in the
      HTSA versus the LTSA participants, autonomic measures showed comparable
      reactivity, habituation, and recovery in the two anxiety groups. These results
      suggest minimal autonomic differences between HTSA and LTSA individuals, thus
      supporting theories of social anxiety that emphasize cognitive factors.

PMID- 14570173
TI  - Sum frequency generation studies on the surface structures of plasticized and
      unplasticized polyurethane in air and in water.
AB  - This study characterizes the molecular surface structures of polyurethane (PU)
      and plasticized PU films in air, in water, and in albumin solution in situ using
      a nonlinear optical technique, sum frequency generation (SFG) vibrational
      spectroscopy. Two different plasticizers are investigated: dioctyl sebacate (DOS)
      and o-nitrophenyl octyl ether (NPOE). Plasticization of PU is common for
      biosensors to achieve better adhesion, malleability, elasticity, and
      permeability; however, this can adversely affect biocompatibility. Our research
      indicates that plasticizers can segregate to the PU surface not only in air but
      also in water. In addition, plasticizer content can affect protein adsorption
      behaviors of PU surfaces. This is the first time surface-sensitive SFG has been
      applied to deduce plasticizer surface behavior in situ. More specifically, we
      found that DOS dominates the surface of the film with DOS surface concentrations
      higher than DOS bulk concentrations both in air and in contact with an aqueous
      environment. NPOE has a reduced effect at the surface compared to DOS in both air
      and aqueous environments. Addition of either DOS or NPOE to PU was also found to
      cause a change in albumin adsorption.

PMID- 14570174
TI  - In line desalting mass spectrometry for the study of noncovalent biological
      complexes.
AB  - Electrospray ionization-mass spectrometry is becoming widely used as a high
      throughput method for the study of biomolecular interactions. It allows for the
      analysis of complexes from heterogeneous mixtures with high sensitivity and
      selectivity. In many cases, biomolecules and their complexes must be stored in
      nonvolatile salt buffers and other solubilizing agents, such as organics or
      detergents, to maintain stability and integrity. To ensure an efficient
      electrospray process, desalting and exchanging the biomolecular solutions into a
      volatile buffer is imperative. Current off-line or on-line methods to accomplish
      this are time-consuming, frequently disrupt noncovalent interactions, and can
      result in considerable sample loss. Here we describe a simple, general, and
      highly efficient, rapid in-line desalting approach using a small gel cartridge to
      assist in the mass spectrometric analysis of biomolecules and their complexes.
      Though the method has broad applicability, we focus our analysis on proteins and
      demonstrate its usefulness by examining protein-metal, protein-protein, protein
      DNA, and protein-RNA interactions. The method is shown to provide rapid direct
      analysis of analyte solutions containing salts, glycerol, organics, and
      involatile buffers without deleterious effects.

PMID- 14570175
TI  - Doping control analysis of bovine hemoglobin-based oxygen therapeutics in human
      plasma by LC-electrospray ionization-MS/MS.
AB  - Since January 2000, hemoglobin-based oxygen carriers, such as Hemopure, belong to
      the list of prohibited substances of the International Olympic Committee.
      Hemopure is based on bovine hemoglobin, which is intra- and intermolecularly
      cross-linked by glutaraldehyde units causing an average molecular weight of
      approximately 250,000. Bovine and human hemoglobins differ by 15% in amino acid
      sequence; hence, tryptic digestion of these proteins generates species-common and
      -unique peptides. Those specific fragments originate from the alpha- and beta
      subunits of hemoglobin, such as bovine Hb peptides alpha(69-90) (2367.2 Da) or
      beta(40-58) (2089.9 Da). By means of LC-MS/MS, peptides of human and bovine
      hemoglobin can be separated and identified, enabling the determination of
      compounds based on Hb of bovine origin and thus the administration of oxygen
      carriers such as Hemopure. Blank plasma samples were spiked with Hemopure or
      human or bovine hemoglobin, filtered, enzymatically digested, and analyzed on an
      Agilent 1100 Series HPLC interfaced to an Applied Biosystems API 2000 triple
      quadrupole mass spectrometer. In plasma aliquots of 50 microL containing 50
      microg of Hemopure (1 mg/mL), peptides of bovine hemoglobin were confirmed, and
      blank plasma samples as well as 68 specimens of high-performance athletes were
      tested with the developed procedure.

PMID- 14570176
TI  - Real-time impedance measurements during electrochemical experiments and their
      application to aniline oxidation.
AB  - Development of an in situ technique for measuring electrochemical impedance
      spectra in real time during an electrochemical experiment is described. The
      technique is based on staircase voltammetry with relatively large step heights,
      in which a series of increasing potential steps are applied to an electrochemical
      system, and the resulting currents are sampled. The first derivatives of the
      currents thus obtained are then converted to ac current signals in frequency
      domain, and impedances are computed from them. To demonstrate the technique as a
      tool for studying the electrode/electrolyte interface during the electrochemical
      reaction, we chose an electrochemical oxidation reaction of aniline, whose
      reaction products have been known to continuously change the electrode surface
      due to the polymer film growth on its surface, and report a number of
      observations that would not have been obtained without such in situ experiments.
      A suggestion is also made on the use of staircase voltammetry for mechanistic
      studies on complex electrochemical reactions by simply varying the sampling time.

PMID- 14570177
TI  - A microchip electrophoresis device with integrated electrochemical detection: a
      direct comparison of constant potential amperometry and sinusoidal voltammetry.
AB  - A microchip electrophoresis system with integrated electrochemical detection is
      described in this work. The hybrid device utilizes poly(dimethylsiloxane) as the
      electrophoresis channel substrate and a planar gold electrode lithographically
      fabricated onto a glass slide for electrochemical detection. The system is
      characterized by the separation and detection of various neurotransmitters. The
      gold working electrode is placed just inside the separation channel without
      adverse effects on the detection sensitivity, due to the electrical decoupling of
      the detection and electrophoresis systems. The close proximity of the working
      electrode to the exit of the separation channel results in symmetric peak shapes
      and efficient separations (50,000-100,000 plates/m). A direct comparison between
      the frequency-based electrochemical technique, sinusoidal voltammetry, and the
      more commonly used constant potential (DC) amperometry is made. Sinusoidal
      voltammetry is found to be roughly an order of magnitude more sensitive than DC
      amperometry, with calculated mass detection limits (S/N = 3) of 12 amol and 15
      amol for dopamine and isoproterenol, respectively.

PMID- 14570178
TI  - Picoamperometric detection of glucose at ultrasmall platinum-based biosensors:
      preparation and characterization.
AB  - A simple method is described for the construction of a glucose biosensor with
      good reproducibility. After electrochemical etching, the sensing tip of an etched
      platinum microelectrode was insulated using a synthetic rubber dip coating. The
      insulating layer was then heat-cured, leading to a small exposed area at the very
      end of the etched Pt tip, as confirmed by scanning electron microscopy. Phenol
      and 2-allylphenol were electropolymerized to form an extra insulating layer that
      effectively retained glucose oxidase (GOX) on the sensing tip of the electrode.
      On the basis of cyclic voltammetry measurements, the apparent radius of the
      biosensor tip was estimated to be between 10 and 500 nm, depending on GOX
      loading. With operational and storage stabilities over 3 weeks, the glucose
      biosensor prepared using optimal GOX concentration (10 mg/mL) exhibited a
      picoamperometric current response within approximately 2 s and a detection limit
      of 20 microM with excellent reproducibility.

PMID- 14570179
TI  - Microfabricated on-chip-type electrochemical flow immunoassay system for the
      detection of histamine released in whole blood samples.
AB  - This paper describes an on-chip-type electrochemical flow immunoassay system with
      a multichanneled matrix column. The multichanneled matrix column was functionally
      coated with cation-exchange resin and used for separation of proteins.
      Antihistamine immunoglobulin G (IgG) antibody conjugated with
      ferrocenemonocarboxylic acid (Fc) was also prepared and used as a novel
      analytical reagent. Antibody-antigen complexes were separated from free Fc
      conjugated IgG antibody (Fc-IgG) on the basis of differences in isoelectric point
      (pI) using the multichanneled matrix column coated with cation-exchange resin.
      The assay yields a good relationship between current and histamine concentration
      in the range of 200-2000 ng/mL. This simple technique enables the assay of
      histamine released in whole blood within 2 min. Furthermore, a good correlation
      was found between the response of the electrochemical immunoassay described in
      this paper and the conventional RIA (radioimmunoassay). This on-chip-type
      electrochemical flow immunoassay requires only minute quantities of whole blood
      samples and generates highly reproducible results.

PMID- 14570180
TI  - Development of chemical sensors based on redox-dependent receptors: N,N'
      dimethyldiazapyrenium-modified electrodes.
AB  - Electrodes modified with Nafion films containing 2,7-dimethyldiazapyrenium
      (DAP2+) were prepared and characterized with voltammetry by themselves and in the
      presence of organic substrates. The large, planar, electron-poor aromatic surface
      in DAP2+ facilitates pi-stacking interactions with other planar aromatic
      molecules, particularly those that are negatively charged or electron-rich.
      Previous studies showed that the reduction of DAP2+ decreases the strength of
      these interactions, making the binding redox-dependent, and resulting in negative
      shifts in the E(1/2) of DAP2+/+. This study shows that the redox-dependent
      binding ability of DAP2+ is retained in Nafion, but the selectivity is
      considerably different. Most significantly, the electron-rich, neutral aromatic
      compounds that produced small shifts in the E(1/2) of DAP2+/+ in solution cause
      much larger shifts, up to -110 mV, with the modified electrodes. With indole as a
      substrate, Nernstian behavior is observed (-60 mV shift per log[indole]) between
      10 and 0.5 mM.

PMID- 14570181
TI  - A generalized model for apparently "non-Nernstian" equilibrium responses of
      ionophore-based ion-selective electrodes. 1. Independent complexation of the
      ionophore with primary and secondary ions.
AB  - A generalized model that describes apparently "non-Nernstian" equilibrium
      responses of ionophore-based ion-selective electrodes (ISEs) is presented. It is
      formulated for primary and secondary ions of any charges that enter the membrane
      phase and independently form complexes with the ionophore, respectively.
      Equations for the phase boundary potential model were solved numerically to
      obtain whole response curves as a function of the sample activity of the primary
      ion, and analytical solutions could be obtained for apparently non-Nernstian
      response sections in these response curves. Ionophore-based ISEs can give three
      types of apparently non-Nernstian equilibrium responses, i.e., apparently "super
      Nernstian", "inverted-Nernstian", and "sub-Nernstian" responses. The values of
      the response slopes depend on the charge numbers of the primary and secondary
      ions and on the stoichiometries of their complexes with the ionophore. The
      theoretical predictions for super-Nernstian responses agree well with the
      experimental results obtained with ISEs based on acidic ionophores or
      metalloporphyrin ionophores. Also, theoretical response curves with inverted
      Nernstian slopes were found to be similar in character to the pH responses of
      Ca2+-selective electrodes based on organophosphate ionophores, which have been
      known to exhibit a so-called "potential dip". The quantitative understanding of
      apparently non-Nernstian response slopes presented here provides an insight into
      ionophore-analyte complexation processes in ISE membranes and should be helpful
      for the design of new ionophores.

PMID- 14570182
TI  - Fibroblast cells: a sensing bioelement for glucose detection by impedance
      spectroscopy.
AB  - Modifying the electrical properties of fibroblasts against various glucose
      concentrations can serve as a basis for a new, original sensing device. The aim
      of the present study is to test a new biosensor based on impedancemetry
      measurement using eukaryote cells. Fibroblast cells were grown on a small
      optically transparent indium tin oxide semiconductor electrode. Electrochemical
      impedance spectroscopy (EIS) was used to measure the effect of D-glucose on the
      electrical properties of fibroblast cells. Further analyses of the EIS results
      were performed using equivalent circuits in order to model the electrical flow
      through the interface. The linear calibration curve was established in the range
      0-14 mM. The specification of the biosensors was verified using cytochalasin B as
      an inhibitor agent of the glucose transporters. The nonreactivity to sugars other
      than glucose was demonstrated. Such a biosensor could be applied to a more
      fundamental study of cell metabolism.

PMID- 14570183
TI  - Microchip electrophoresis of tagged probes incorporated with one-colored ddNTP
      for analyzing single-nucleotide polymorphisms.
AB  - We demonstrate a simple and rapid method for SNP typing, allele frequency
      determination, and trace mutant analysis that works with even an inexpensive
      detection system. This method is based on microchip electrophoresis of tagged
      probes incorporated with one-colored ddNTP (METPOC). The assay uses dye
      terminator incorporation into a pair of probes of different lengths specific to
      wild- and mutant-type targets, respectively. They are hybridized to the targets
      prior to ddNTP-Cy-5 incorporation, which occurs only for a matched probe-target
      duplex. Because the extension reactions for the two probes are carried out
      simultaneously in one tube and the products from both probes are analyzed in one
      channel by one-color fluorescence detection, an accurate comparative analysis of
      SNPs is possible. SNP typing as well as allele frequency determination in the
      range above 0.1% can easily be carried out using a commercial microchip
      electrophoresis system in a few minutes.

PMID- 14570184
TI  - Dispersion reduction in open-channel liquid electrochromatographic columns via
      pressure-driven back flow.
AB  - Application of electrokinetic forces to drive the mobile phase diminishes analyte
      dispersion in open-channel liquid chromatographic columns due to minimization of
      shear in the flow field. However, the retentive layer coating the inner walls of
      such devices slows down the average convective velocity of solute molecules in
      its vicinity, inherently causing dispersion of analyte bands. In this article, we
      explore the possibility of reducing such dispersion in electrochromatographic
      columns by imposing a pressure-driven back flow in the system. Analysis shows
      that although such a strategy introduces shear in the flow field, the overall
      dispersion in the mobile phase is reduced. This occurs as the streamline velocity
      in such a system is greater near the channel walls than that in the center of the
      conduit, thereby allowing fluid dispersion to counteract wall retention effects.
      For an optimally chosen magnitude of the back flow, hydrodynamic dispersion of
      any target species in the mobile phase may be shown to diminish by a factor of 3
      and 10/3 in a circular tube and a parallel-plate geometry, respectively. A
      similar reduction in slug dispersion is also realized in rectangular conduits for
      all aspect ratios. In trapezoidal geometries with large wedge angles or
      isotropically etched profiles, this reduction factor may attain values of 10 or
      greater.

PMID- 14570185
TI  - Structure-function relationships in high-density octadecylsilane stationary
      phases by Raman spectroscopy. 3. Effects of self-associating solvents.
AB  - Raman spectroscopy is used to examine the subtle effects of polar, hydrogen
      bonding solvents; temperature; and the surface grafting method (surface- or
      solution-polymerized) on alkyl chain rotational and conformational order in a
      series of high-density octadecylsilane stationary phases ranging in surface
      coverage from 3.09 to 6.45 micromol/m2. Rotational and conformational order is
      assessed using the intensity ratio of the antisymmetric to symmetric v(CH2) modes
      as well as the frequencies at which these Raman bands are observed. Alkyl
      rotational and conformational order decreases with decreasing surface coverage in
      these polar solvents, consistent with the behavior of these materials in air. For
      homogeneously distributed, high surface coverage materials, these polar solvents
      induce rotational ordering that is proposed to be due to the self-association of
      these solvents through hydrogen bonding or other dipole interactions at the
      alkylsilane-solvent interface. From these observations, molecular pictures of
      these solvent-stationary-phase interfaces are proposed in which solvent
      interaction with the stationary phase occurs primarily at the distal methyl group
      of the alkyl chains.

PMID- 14570186
TI  - Structure-function relationships in high-density octadecylsilane stationary
      phases by Raman spectroscopy. 4. Effects of neutral and basic aromatic compounds.
AB  - The effects of aromatic compounds (toluene, benzene, p-xylene, anisole, aniline,
      and pyridine), temperature, and surface grafting method (surface- or solution
      polymerized) on alkyl chain rotational and conformational order in a series of
      high-density octadecylsilane stationary phases ranging in surface coverage from
      3.09 to 6.45 micromol/m2 are examined by Raman spectroscopy. Rotational and
      conformational order are assessed using the intensity ratio of the antisymmetric
      to symmetric v(CH2) modes as well as the frequency at which the symmetric v(CH2)
      band is observed. Alkyl rotational and conformational order decrease with
      decreasing surface coverage in these aromatic compounds, which is consistent with
      the behavior of these materials in air and in other solvents. In addition, order
      of the alkyl chains is dependent on solvent hydrophobicity, hydrogen-bonding
      ability, and basicity. The most hydrophobic compounds impart disorder to the
      stationary phase; the hydrogen-bonding aromatics increase the rotational order of
      homogeneously distributed, high-surface-coverage materials; and basic aromatic
      compounds increase the conformational order of high- and low-coverage materials
      as the basic compounds undergo silanophilic interactions with exposed surface
      silanols. From these observations, molecular pictures of the chromatographic
      interface that display interactions between the alkyl chains and these aromatic
      compounds are proposed.

PMID- 14570187
TI  - On-line continuous-flow, multi-protein biochemical assays for the
      characterization of bioaffinity compounds using electrospray quadrupole time-of
      flight mass spectrometry.
AB  - The applicability of a homogeneous on-line continuous-flow, multi-protein
      biochemical assay was demonstrated for the interaction between fluorescein-biotin
      and streptavidin and for digoxin and anti-digoxigenin using electrospray
      quadrupole time-of-flight mass spectrometry (Q-TOF MS). In the on-line continuous
      flow biochemical MS-based system several receptors (e.g., streptavidin and anti
      digoxigenin, respectively) were allowed to react with corresponding reporter
      ligands (e.g.,fluorescein-biotin and digoxin, respectively). The methodology
      presented allows the simultaneous measurement of affinity and molecular mass of
      an active compound. By using automated MS and MS-MS switching functions of the Q
      TOF, structure information is obtained allowing the characterization of bioactive
      compounds. No cross-reactivities were observed between the two model systems
      fluorescein-biotin/streptavidin and digoxin/anti-digoxigenin.

PMID- 14570188
TI  - Identification of protein ligands in complex biological samples using intensity
      fading MALDI-TOF mass spectrometry.
AB  - The easy detection of biomolecular interactions in complex mixtures using a
      minimum amount of material is of prime interest in molecular and cellular biology
      research. In this work, a mass spectrometry MALDI-TOF based approach, which we
      call intensity-fading (IF MALDI-TOFMS), and which was designed for just such a
      purpose, is reported. This methodology is based on the use of the MALDI ion
      intensities to detect quickly the formation of complexes between nonimmobilized
      biomolecules in which a protein is one of the partners (protein-protein, protein
      peptide, protein-organic molecule, and protein-nucleic acid complexes). The
      complex is detected through the decrease (fading) of the molecular ion
      intensities of the partners as directly compared to the MALDI mass spectrum of
      the mixture (problem and control molecules) following the addition of the target
      molecule. The potential of the approach is examined in several examples of model
      interactions, mainly involving small nonprotein and protein inhibitors of
      proteases, at both the qualitative and semiquantitative levels. Using this
      method, different protein ligands of proteolytic enzymes in total extracts of
      invertebrate organisms have been identified in a simple way. The proposed
      procedure should be easily applied to the high-throughput screening of
      biomolecules, opening a new experimental strategy in functional proteomics.

PMID- 14570189
TI  - A preconcentration/matrix reduction method for the analysis of rare earth
      elements in seawater and groundwaters by isotope dilution ICPMS.
AB  - A simple method of simultaneous preconcentration and matrix reduction was
      developed for the analysis of rare earth elements (REEs) in seawater and
      groundwater by ID ICPMS. The method utilizes partitioning of the REEs with solid
      hydroxides to separate them from soluble matrix species (e.g., Ba2+, NOM,
      seawater salts). Acidified samples were spiked and equilibrated with an enriched
      isotope cocktail (142Ce, 145Nd, 161Dy, 171Yb). Aqueous NH3 was then added to the
      spiked samples to induce the coprecipitation of the REEs with a small fraction of
      the natural Mg2+ as Mg(OH)2. The samples were centrifuged and the precipitate was
      rinsed to remove more than 99.8% of the Ba2+ along with the matrix salts. The
      precipitate was dissolved in 400 microL of 10% HNO3 for ICPMS analysis. The four
      spiked elements, determined by isotope dilution, served as internal standards for
      the remaining REEs. Analysis of NASS-4 and NASS-5 seawater reference materials
      showed good agreement with published values. Calculated limits of detection for a
      1.65-g sample ranged from 0.1 pg/g for the light REEs to 0.02 pg/g for the heavy
      REEs. The reagent blanks ranged from a high of 0.28 pg/sample for Ce to a low of
      0.0036 pg/sample for Tb.

PMID- 14570190
TI  - Rationalization of retention and overloading behavior of basic compounds in
      reversed-phase HPLC using low ionic strength buffers suitable for mass
      spectrometric detection.
AB  - The retention and overloading behavior of some basic (and acidic) compounds has
      been studied on different RP-HPLC columns in buffers of varying ionic strength.
      Anomalous retention patterns of acids and bases were found on one phase in low
      pH, volatile buffers such as formic acid, favored for mass spectrometric
      analysis. Unusual retention compared to that in higher ionic strength phosphate
      buffers is attributed to the presence of positively charged sites existing on
      this phase at low pH. Overloading of bases as well as acids is shown to be a
      function of mobile-phase ionic strength. This result is a logical consequence of
      previous suggestions that mutual repulsion of ions held on the hydrophobic
      surface of the stationary phase, rather than overload of silanols, is largely
      responsible for overloading on pure silica RP columns. Thus, overloading occurs
      much more readily in low ionic strength formic acid buffers. Appreciable loss of
      efficiency can occur in such buffers when only 50 ng of some bases is analyzed on
      a standard-sized column.

PMID- 14570191
TI  - Dual electrospray ionization source for confident generation of accurate mass
      tags using liquid chromatography Fourier transform ion cyclotron resonance mass
      spectrometry.
AB  - Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) has
      rapidly established a prominent role in proteomics because of its unparalleled
      resolving power, sensitivity and ability to achieve high mass measurement
      accuracy (MMA) simultaneously. However, space-charge effects must be
      quantitatively, routinely, and confidently corrected because they are known to
      profoundly influence MMA. We argue that the most effective way to account for
      space-charge effects is to introduce an internal mass calibrant (IMC) using a
      dual electrospray ionization (ESI) source where the IMC is added from a separate
      ESI emitter. The major disadvantage of our initial dual ESI source to achieve
      high MMA, and arguably the only one, was the time required to switch between the
      analyte emitter and IMC emitter (i.e., >300 ms). While this "switching time" was
      acceptable for direct infusion experiments, it did not lend itself to high
      throughput applications or when conducting on-line liquid separations. In this
      report, we completely redesigned the dual ESI source and demonstrate several key
      attributes. First, the new design allows for facile alignment of ESI emitters,
      undetectable vibration, and the ability to extend to multiple emitters. Second,
      the switching time was reduced to <50 ms, which allowed the analyte and IMC to be
      accumulated "simultaneously" in the external ion reservoir and injected as a
      single ion packet into the ion cyclotron resonance cell, eliminating the need for
      a separate accumulation and ion injection event for the IMC. Third, by using a
      high concentration of the IMC, the residence time on this emitter could be
      reduced to approximately 80 ms, allowing for more time spent accumulating analyte
      ions of significantly lower concentration. Fourth, multiplexed on-line
      separations can be carried out providing increased throughput. Specifically, the
      new dual ESI source has demonstrated its ability to produce a stable ion current
      over a 45-min time period at 7 T resulting in mass accuracies of 1.08 ppm +/-
      0.11 ppm (mean +/- confidence interval of the mean at 95% confidence; N = 160).
      In addition, the analysis of a tryptic digest of apomyoglobin by nanoLC-dual ESI
      FT-ICR afforded an average MMA of -1.09 versus -74.5 ppm for externally
      calibrated data. Furthermore, we demonstrate that the amplitude of a peptide
      being electrosprayed at 25 nM can be linearly increased, ultimately allowing for
      dynamic analyte/IMC abundance modulation. Finally, we demonstrate that this
      source can reliably be used for multiplexing measurements from two (eventually
      more) flow streams.

PMID- 14570192
TI  - An automated matrix-assisted laser desorption/ionization quadrupole Fourier
      transform ion cyclotron resonance mass spectrometer for "bottom-up" proteomics.
AB  - Here we describe a new quadrupole Fourier transform ion cyclotron resonance
      hybrid mass spectrometer equipped with an intermediate-pressure MALDI ion source
      and demonstrate its suitability for "bottom-up" proteomics. The integration of a
      high-speed MALDI sample stage, a quadrupole analyzer, and a FT-ICR mass
      spectrometer together with a novel software user interface allows this instrument
      to perform high-throughput proteomics experiments. A set of linearly encoded
      stages allows sub-second positioning of any location on a microtiter-sized target
      with up to 1536 samples with micrometer precision in the source focus of the ion
      optics. Such precise control enables internal calibration for high mass accuracy
      MS and MS/MS spectra using separate calibrant and analyte regions on the target
      plate, avoiding ion suppression effects that would result from the spiking of
      calibrants into the sample. An elongated open cylindrical analyzer cell with trap
      plates allows trapping of ions from 1000 to 5000 m/z without notable mass
      discrimination. The instrument is highly sensitive, detecting less than 50 amol
      of angiotensin II and neurotensin in a microLC MALDI MS run under standard
      experimental conditions. The automated tandem MS of a reversed-phase separated
      bovine serum albumin digest demonstrated a successful identification for 27
      peptides covering 45% of the sequence. An automated tandem MS experiment of a
      reversed-phase separated yeast cytosolic protein digest resulted in 226
      identified peptides corresponding to 111 different proteins from 799 MS/MS
      attempts. The benefits of accurate mass measurements for data validation for such
      experiments are discussed.

PMID- 14570193
TI  - Imaging of membrane lipids in single cells by imprint-imaging time-of-flight
      secondary ion mass spectrometry.
AB  - A new method for identification and localization of organic molecules in
      biological samples is described. The method involves making an imprint of a
      biological sample on a silver (Ag) surface and subsequent analysis of the imprint
      by imaging time-of-flight secondary ion mass spectrometry (TOF-SIMS). Using this
      method, detection of unfragmented, Ag cationized molecules at a spatial
      resolution of <0.5 microm is possible. We have used the method to study the
      spatial distribution of phosphatidylcholine and cholesterol in blood cells
      adhering to a glass surface. The TOF-SIMS images show that cholesterol is
      preferentially located in the plasma membrane, whereas the phosphocholine shows
      highest concentration in the nuclear membrane. Scanning electron microscopy and
      fluorescence microscopy images show that the amount of transferred material
      during the imprinting process can be controlled by varying the imprinting
      pressure and pretreatment of the cell substrate prior to imprinting.

PMID- 14570194
TI  - Application of femtosecond laser ablation time-of-flight mass spectrometry to in
      depth multilayer analysis.
AB  - A femtosecond laser system was used in combination with a time-of-flight mass
      spectrometer (TOF-MS) for in-depth profiling of semiconductor and metal samples.
      The semiconductor sample was a Co-implanted (10(17) ions/cm3) silicon wafer that
      had been carefully characterized by other established techniques. The total depth
      of the shallow implanted layer was 150 nm. As a second sample, a thin film metal
      standard had been used (NIST 2135c). This standard consisted of a silicon wafer
      with nine alternating Cr and Ni layers, each having a thickness of 56 and 57 nm,
      respectively. An orthogonal TOF-MS setup was implemented. This configuration was
      optimized until a sufficient mass resolution of 300 (m/delta m) and sensitivity
      was achieved. The experiments revealed that femtosecond-laser ablation TOF-MS is
      capable of resolving the depth profiles of these demanding samples. The poor
      precision of the measurements is discussed, and it is shown that this is due to
      pulse-to-pulse stability of the current laser system. Femtosecond-laser ablation
      TOF-MS is shown to be a promising technique for rapid in-depth profiling with a
      good lateral resolution of various multilayer thin film samples.

PMID- 14570195
TI  - Metallic colloid wavelength-ratiometric scattering sensors.
AB  - Gold and silver colloids display strong colors as a result of electron
      oscillations induced by incident light, which are referred to as the plasmon
      absorption. This absorption is dependent on colloid-colloid proximity, which has
      been the basis of absorption assays using colloids. We now describe a new
      approach to optical sensing using the light scattering properties of colloids.
      Colloid aggregation was induced by avidin-biotin interactions, which shifted the
      plasmon absorption to longer wavelengths. We found the spectral shift results in
      changes in the scattering at different incident wavelengths. By measuring the
      ratio of scattered intensities at two incident wavelengths, this measurement was
      made independent of the total colloid concentration. The high scattering
      efficiency of the colloids resulted in intensities equivalent to fluorescence
      when normalized by the optical density of the fluorophore and colloid. This
      approach can be used in a wide variety of assay formats, including those commonly
      used with fluorescence detection.

PMID- 14570196
TI  - A reusable flow-through polymerase chain reaction instrument for the continuous
      monitoring of infectious biological agents.
AB  - Continuous monitoring of the environment for infectious diseases and related
      biowarfare agents requires the implementation of practical cost-effective
      methodologies that are highly sensitive and specific. One compatible method
      employed in clinical diagnostics is real-time polymerase chain reaction (PCR)
      analysis. The utility of this technique for environmental monitoring is limited,
      however, by the utilization of single-use consumables in commercial PCR
      instruments. This greatly increases mechanical complexity, because sophisticated
      robotic mechanisms must replenish the disposable elements. An alternative
      strategy develops an autonomous monitoring system consisting of reusable modules
      that readily interface with fluidic circuitry in a flow-through scheme. The
      reduced complexity should increase reliability while decreasing operating costs.
      In this report, we describe a reusable, flow-through PCR module that functions as
      one component in such a system. This module was rigorously evaluated with
      Bacillus anthracis genomic DNA and demonstrated high repeatability, sensitivity,
      and efficiency, with no evidence of sample-to-sample carryover.

PMID- 14570197
TI  - Genetic engineering of an allosterically based glucose indicator protein for
      continuous glucose monitoring by fluorescence resonance energy transfer.
AB  - Real-time monitoring of blood glucose could vastly reduce a number of the long
      term complications associated with diabetes. In this article, we present a novel
      approach that relies on a glucose-binding protein engineered such that a 20%
      reduction in fluorescence due to the fluorescence resonance energy transfer
      occurs as a result of glucose binding. This change in fluorescence provides a
      signal for the optical detection of glucose. The novel glucose indicator protein
      (GIP) was created by fusing two fluorescent reporter proteins (green fluorescent
      proteins) to each end of an Escherichia coli glucose-binding protein in such a
      manner that the spatial separation between the fluorescent moieties changes when
      glucose binds, thus generating a distinct optical signal that can be used for
      glucose detection. By placing the GIP within a dialysis hollow fiber sensor, a
      microsensor has been developed for continuous monitoring of glucose. The sensor
      had a response time to sudden glucose changes within 100 s and was reversible.
      The sensor was shown to have an optional range on the order of 10 microM of
      glucose.

PMID- 14570198
TI  - Multivariate analysis and classification of the chemical quality of 7
      aminocephalosporanic acid using near-infrared reflectance spectroscopy.
AB  - The capability of near-infrared (NIR) spectroscopy in comparison to conventional
      chemical testing to control the chemical quality of a pharmaceutical intermediate
      has been investigated. Multivariate projection methods including principal
      component analysis, partial least-squares discriminant analysis and soft
      independent modeling of class analogy have been evaluated. 7-Aminocephalosporanic
      acid has been chosen as an example providing a large variation of quality due to
      its relative chemical instability. Three sets of production lots have been
      selected to study the extent of quality information extractable from NIR spectra.
      The first set of 91 lots covers a very broad range of chemical quality assessed
      by 8 parameters with a partially extended characterization by physical
      properties. The general congruence of spectral, chemical, and physical
      information has been investigated. The second set of 110 lots covers a very
      narrow range of chemical quality assessed by 11 parameters. With extended quality
      information, the intrinsic selectivity within the spectral data structure has
      been studied. The third set of 228 lots characterized by 8 parameters is a
      selection out of more than 1000 lots over a production period of two years. The
      ruggedness of the multivariate approach has been confirmed by a cross validation
      of the classification test.

PMID- 14570199
TI  - Imaging of Zn2+ release from pancreatic beta-cells at the level of single
      exocytotic events.
AB  - Regulated secretion of Zn2+ from isolated pancreatic beta-cells was imaged using
      laser-scanning confocal microscopy. In the method, beta-cells were incubated in a
      solution containing the novel fluorescent Zn2+ indicator FluoZin-3. Zn2+ released
      from the cells reacted with the dye to form a fluorescent product, which was
      detected by the confocal microscope. The new dye is much brighter than Zinquin,
      previously used for this application, allowing detection limits of 10-40 nM and
      temporal resolution of 16 ms/image. The high temporal resolution allowed imaging
      of isolated fluorescent transients that occurred at the edge of the cells
      following stimulation with 20 mM glucose or 40 mM K+. Fluorescent transients took
      16-50 ms to reach a peak from the initial rise and returned to baseline after 170
      +/- 50 ms (n = 78 transients from 15 cells). It was concluded that the transients
      correspond to detection of exocytotic release of Zn2+. Analysis of the temporal
      and spatial dispersion of the transients indicates that the release of Zn2+ is
      not diffusion limited but is instead kinetically controlled in agreement with
      previous observations of insulin release detected by amperometry.

PMID- 14570200
TI  - Collection of trace amounts of DNA/mRNA molecules using genomagnetic
      nanocapturers.
AB  - The collection and then the separation of rare DNA/mRNA targets with single-base
      mismatches in a complex matrix is critically important in human disease
      diagnostics, gene expression studies, and gene profiling. The major result of
      this work is the development and application of a novel genomagnetic nanocapturer
      (GMNC) for the collection, separation, and detection of trace amounts of DNA/RNA
      molecules with one single-base difference. The GMNC is constructed by
      bioconjugating molecular beacon DNA probes onto magnetic nanoparticle surfaces.
      We have successfully applied the GMNC in artificial buffer solution samples and
      in cancer cell samples, both containing different proteins and random DNA
      sequences. Our method has three distinctly useful features: highly efficient
      collection of trace amount of DNA/mRNA samples down to femtomolar (10(-15) M)
      concentrations; excellent ability to differentiate single-base-mismatched
      DNA/mRNA samples by combining the exceptional specificity of molecular beacons
      and the separation power of magnetic nanoparticles; and real-time monitoring and
      confirmation of the collected gene products. The newly developed genomagnetic
      nanocapturers will be highly useful for the collection of trace amounts of
      DNA/mRNA targets in a variety of sample sources in forensic, medical, and
      biotechnological fields.

PMID- 14570201
TI  - An automated orthogonal two-dimensional liquid chromatograph.
AB  - A simple approach to two-dimensional liquid chromatography has been developed by
      coupling columns of different selectivity using a 12-port, dual-position valve
      and a standard HPLC system. The valve at the junction of the two columns enables
      continuous, periodic sampling (injection) of the primary column eluent onto the
      secondary column. The separation in the primary dimension is comparable to
      conventional HPLC, whereas the secondary column separation is fast, lasting
      several seconds. The high-speed separation in the secondary dimension enables the
      primary column eluent to be sampled with fidelity onto the secondary column
      throughout the chromatographic run. One might expect a coupled column liquid
      chromatography system operating in reverse-phase mode to be strongly correlated
      and, hence, inefficient. However, by applying a solvent gradient in the primary
      dimension and by progressively incrementing the solvent strength in the secondary
      dimension (tuning), the inefficiency or cross correlation between the two
      dimensions is minimized. In a tuned two-dimensional system, the influence of
      primary column retention (usually hydrophobicity) is minimal on secondary column
      retention. This enables subtle differences in component interaction with the two
      stationary phases to dominate the secondary column retention. The peaks are
      randomly dispersed over a retention plane rather than along a diagonal, resulting
      in an orthogonal separation. The peak capacity is multiplicative, and each
      component has a unique pair of retention times, enabling positive identification.
      In addition, the location of the component provides two independent measures of
      molecular properties. The 2D-LC system was evaluated by analyzing a test mixture
      made of some aromatic amines and non-amines on different secondary columns (ODS
      AQ/ODS monolith, ODS/amino, ODS/cyano). The relative location of sample
      components in the two-dimensional plane varied significantly with change in
      secondary column. Among the secondary columns, the amino and cyano columns
      offered the most complementary separation, with the retention order of several
      components reversed in the secondary dimension. The theoretical peak capacity of
      the 2D-LC system was around 450 for a separation lasting 30 min. A 2D-LC system
      involving amino and cyano columns resulted in a high-speed separation of the test
      mixture, with most of the chemical components resolved within a few minutes.

PMID- 14570202
TI  - Cell cycle-dependent protein fingerprint from a single cancer cell: image
      cytometry coupled with single-cell capillary sieving electrophoresis.
AB  - Study of cell cycle-dependent protein expression is important in oncology, stem
      cell research, and developmental biology. In this paper, we report the first
      protein fingerprint from a single cell with known phase in the cell cycle. To
      determine that phase, we treated HT-29 colon cancer cells with Hoescht 33342, a
      vital nuclear stain. A microscope was used to measure the fluorescence intensity
      from one treated cell; in this form of image cytometry, the fluorescence
      intensity is proportional to the cell's DNA content, which varies in a
      predictable fashion during the cell cycle. To generate the protein fingerprint,
      the cell was aspirated into the separation capillary and lysed. Proteins were
      fluorescently labeled with 3-(2-furoylquinoline-2-carboxaldehyde, separated by
      capillary sieving electrophoresis, and detected by laser-induced fluorescence.
      This form of electrophoresis is the capillary version of SDS-PAGE. The single
      cell electropherogram partially resolved approximately 25 components in a 30-min
      separation, and the dynamic range of the detector exceeded 5000. There was a
      large cell-to-cell variation in protein expression, averaging 40% relative
      standard deviation across the electropherogram. The dominant source of variation
      was the phase of the cell in the cell cycle; on average, approximately 60% of the
      cell-to-cell variance in protein expression was associated with the cell cycle.
      Cells in the G1 and G2/M phases of the cell cycle had 27 and 21% relative
      standard deviations in protein expression, respectively. Cells in the G2/M phase
      generated signals that were twice the amplitude of the signals generated by G1
      phase cells, as expected for cells that are soon to divide into two daughter
      cells. When electropherograms were normalized to total protein content, the
      expression of only one component was dependent on cell cycle at the 99%
      confidence limit. That protein is tentatively identified as cytokeratin 18 in a
      companion paper.

PMID- 14570204
TI  - The XT-tube extractor: a hollow fiber-based supported liquid membrane extractor
      for bioanalytical sample preparation.
AB  - A new supported liquid membrane extractor for bioanalytical sample preparation is
      presented. The extractor consists of a polypropylene hollow fiber mounted inside
      a PTFE tube by means of a cross-connector and a tee-connector. All parts are
      commercially available, inexpensive, and easily assembled. An organic solvent in
      the pores of the fiber forms a liquid membrane that separates the sample, which
      is pumped along the outside of the fiber, from the acceptor phase, which is
      pumped inside. The length of the hollow fiber may easily be varied to meet
      different demands on extractive surface and extract volumes. To test the system,
      the strongly acidic plasticizer/flame retardant metabolite diphenyl phosphate
      ester (DPhP), with a pKa value of 0.26, was extracted from urine. DPhP was
      protonated using 4 M hydrochloric acid and extracted into an acceptor phase at pH
      9. Thirty extractions were made with the same liquid membrane without any
      decrease in extraction efficiency and with a relative standard deviation <7%. An
      analyte concentration enrichment of 5-10 times was achieved in the extraction
      step, giving a limit of detection (S/N = 3) of 0.014 microg/mL with LC/ESI-MS and
      0.18 microg/mL with CE-UV. The effects on extraction efficiency using different
      sample pH, organic solvents, sample flow rates, and lengths of the fiber were
      evaluated.

PMID- 14570203
TI  - Identification of proteins in single-cell capillary electrophoresis fingerprints
      based on comigration with standard proteins.
AB  - In the previous paper in this Journal, we reported the use of capillary sieving
      electrophoresis to characterize proteins expressed by single cancer cells at
      specific phases in the cell cycle. Analysis of the data revealed one component
      with cell cycle-dependent changes in expression at the 99% confidence limit.
      However, the amount of protein present in a single cell is far too small to allow
      its direct identification by mass spectrometry. In this paper, we report a method
      by which such proteins can be tentatively identified. We perform standard SDS
      PAGE electrophoresis of the proteins contained within a homogenate prepared from
      an HT29 cell culture. Proteins extracted from bands in the gel are identified by
      mass spectrometry. The proteins also provide a set of standards that can be used
      to spike the sample before capillary sieving electrophoresis (CSE) separation;
      comigration is taken as evidence for the identity of the target protein. In a
      proof-of-principle experiment, a single band migrating at approximately 47 kDa
      was isolated from the SDS-PAGE gel generated from the HT29 cell line. Proteins
      extracted from this band were used to spike a CSE separation of the same extract.
      This band comigrated with a cell cycle-dependent component identified from single
      cell analysis. In-gel digestion and LC/MS/MS were used to identify five proteins,
      including cytokeratin 18, which is the product of the most highly expressed gene
      in this cell line.

PMID- 14570205
TI  - Alternating voltage capillary electrochromatography.
AB  - A phenomenon was found whereby the application of an alternating voltage to a
      capillary column can vary the capacity factor of a sample solute. The alternating
      voltage-induced variation in the capacity factor was studied using an anion
      exchange mini-bed (a short capillary column 12 mm long). The capacity factor
      varied according to both the amplitude and frequency of an applied alternating
      voltage. The variation greatly depended on the kinds of sample solutes and
      packing materials. A new separation mode for capillary electrochromatography
      using an alternating voltage, that is, alternating voltage capillary
      electrochromatography (AV-CEC), was proposed as an application of this phenomenon
      to control the retention of a sample solute. The chromatographic behavior of
      three organic acids (benzoic acid, phthalic acid, and salicylic acid) was studied
      in AV-CEC using an anion exchange column.

PMID- 14570206
TI  - Sol-gel poly(ethylene glycol) stationary phase for high-resolution capillary gas
      chromatography.
AB  - A sol-gel chemistry-based method was developed for the preparation of highly
      stable capillary gas chromatography (GC) columns with surface-bonded
      poly(ethylene glycol) (PEG) stationary phase. Through a single-step procedure, it
      concurrently provided column deactivation, stationary-phase coating, and chemical
      immobilization of the coated film. Sol-gel reactions were carried out within
      fused-silica capillaries that were filled with properly designed sol solutions
      containing two sol-gel precursors, two different triethoxysilyl-derivatized
      poly(ethylene glycol)s, two sol-gel catalysts, and a deactivation reagent.
      Hydrolytic polycondensation reactions led to the formation of a sol-gel coating
      chemically bonded to the inner walls of the capillary. A number of sol-gel coated
      fused-silica capillary columns were prepared using sol-gel-active PEG
      derivatives. These columns demonstrated many inherent advantages, the main being
      the strong anchoring of the coating to the capillary wall resulting from chemical
      bonding with the silanol groups on the fused-silica capillary inner surface. This
      chemical bonding yielded strongly immobilized PEG coatings with outstanding
      thermal stability (up to 320 degrees C). To our knowledge, such a high thermal
      stability has not been achieved so far on conventionally prepared PEG GC columns.
      Sol-gel PEG columns provided excellent chromatographic performances: high number
      of theoretical plates, excellent run-to-run and column-to-column reproducibility,
      and pronounced selectivity for a wide range of test solutes. Using n-octadecane
      as a test solute (k = 7.14), an efficiency value of 3200 theoretical plates/m was
      obtained on a 10 m x 0.25 mm i.d. fused-silica capillary column. Five sol-gel PEG
      columns provided RSD values of 1.09% for column efficiency (solute, n
      octadecane), 1.37% for retention factor (solute, n-octadecane), and 0.9% for
      separation factor (for solute pair o- and p-xylene). In five replicate
      measurements using the same column, RSD values of less than 0.50% for the
      retention time and 1.36% for retention factor (k) were obtained.

PMID- 14570207
TI  - Experimental studies of electroosmotic flow dynamics during sample stacking for
      capillary electrophoresis.
AB  - Electroosmotic flow dynamics during a field-amplified sample stacking experiment
      have been studied experimentally using the periodic photobleaching of a dilute,
      neutral fluorophore added to the separation buffer. The effects of
      hydrodynamically injecting different sample plug lengths containing a mixture of
      arsenic compounds dissolved in 0.125 mM (120, 240, and 600 s) and 41.7 microM
      (27, 45, and 74 s) phosphate buffer with a separation buffer concentration of
      12.5 mM phosphate buffer were examined. Changes in electroosmotic flow during
      sample stacking and separation were monitored at a rate of 1 Hz. The observed
      effects of increasing the sample plug length on electroosmotic flow and
      electrophoretic current agreed qualitatively with predictions by theoretical
      models presented in the literature. Electroosmotic flow changes on the order of
      100% (1.6-3.3 mm/s) were observed. Broadening of the flow monitoring peaks has
      been used to examine parabolic flow due to the discontinuous buffer systems used
      for sample stacking.

PMID- 14570208
TI  - Thermodynamic and kinetic characterization of polycyclic aromatic hydrocarbons in
      reversed-phase liquid chromatography.
AB  - The retention of six polycyclic aromatic hydrocarbons (PAHs) was characterized by
      reversed-phase liquid chromatography. The PAHs were detected by laser-induced
      fluorescence at four points along an optically transparent capillary column. The
      profiles were characterized in space and time using an exponentially modified
      Gaussian equation. The resulting parameters were used to calculate the retention
      factors, as well as the concomitant changes in molar enthalpy and molar volume,
      for each PAH on monomeric (2.7 micromol/m2) and polymeric (5.4 micromol/m2)
      octadecylsilica. The changes in molar enthalpy become more exothermic as ring
      number increases and as annelation structure becomes less condensed. The changes
      in molar volume become more negative as ring number increases for the planar
      PAHs, but are positive for the nonplanar solutes. In addition, the rate
      constants, as well as the concomitant activation enthalpy and activation volume,
      are calculated for the first time. The kinetic data demonstrate that many of the
      PAHs exhibit very fast transitions between the mobile and stationary phases. The
      transition state is very high in energy, and the activation enthalpies and
      volumes become greater as ring number increases and as annelation structure
      becomes less condensed. The changes in thermodynamic and kinetic behavior are
      much more pronounced for the polymeric phase than for the monomeric phase.

PMID- 14570209
TI  - Vertically stratified flows in microchannels. Computational simulations and
      applications to solvent extraction and ion exchange.
AB  - In this paper, we describe the conditions under which two immiscible fluids flow
      atop one another (viewed perpendicular to the plane on which the channel is
      inscribed) in a shallow microfluidic channel. First, we predict the behavior of a
      two-phase system using fluid dynamic simulations with water-butanol and water
      chloroform as model systems. We numerically model the effect of various physical
      parameters, such as interfacial surface tension, density, viscosity, wall contact
      angle, and flow velocity on the type of flow observed and find that interfacial
      surface tension and viscosity are the parameters responsible for formation of
      vertically stratified, side-by-side, or segmented flows. As predicted by
      numerical simulations, a water-chloroform system never assumes a vertically
      stratified configuration, but a water-butanol system does when the two liquids
      flow at sufficiently high flow velocities. In actual experiments, we test
      conditions under which potentially useful two-phase systems form stable
      vertically stratified flows. We also demonstrate that compared to side-by-side
      flow schemes, shorter diffusion paths are achievable, and thus, the system can be
      used at higher flow rates to obtain the same performance. We then apply such
      findings to practical analytical problems, such as solvent extraction and ion
      exchange.

PMID- 14570210
TI  - Chromatography with dynamically created liquid "stationary" phases: methanol and
      carbon dioxide.
AB  - Liquid films composed of binary mixtures of carbon dioxide and methanol were
      created in empty capillary columns to produce effective stationary phases for
      chromatography. Under certain conditions of temperature, pressure, and
      stoichiometric composition, a binary mobile phase composed of CO2 and an organic
      liquid, such as methanol, can form two immiscible (gas and liquid) phases within
      a chromatographic column. The two phases can coexist in dynamic equilibrium with
      the liquid phase migrating through the column at a slower velocity than the gas
      phase. The liquid phase, composed of methanol saturated with carbon dioxide,
      acted as a chromatographic stationary phase while the gas phase, composed of
      carbon dioxide saturated with methanol, acted as a chromatographic mobile phase.
      The exact conditions necessary for the formation of two phase systems were
      determined from three-dimensional (P, T, XY) phase diagrams calculated from the
      Peng-Robinson cubic equation-of-state using one-parameter mixing rules.
      Separations of simple hydrocarbon mixtures are illustrated under various
      experimental conditions.

PMID- 14570211
TI  - Prediction of the effect of mobile-phase salt type on protein retention and
      selectivity in anion exchange systems.
AB  - This study examines the effect of different salt types on protein retention and
      selectivity in anion exchange systems. Particularly, linear retention data for
      various proteins were obtained on two structurally different anion exchange
      stationary-phase materials in the presence of three salts with different
      counterions. The data indicated that the effects are, for the most part,
      nonspecific, although various specific effects could also be observed.
      Quantitative structure retention relationship (QSRR) models based on support
      vector machine feature selection and regression models were developed using the
      experimental chromatographic data in conjunction with various molecular
      descriptors computed from protein crystal structure geometries. Star plots for
      each descriptor used in the final model were generated to aid in interpretation.
      The resulting QSRR models were predictive, with cross-validated r2 values of
      0.9445, 0.9676, and 0.8897 for Source 15Q and 0.9561, 0.9876, and 0.9760 for Q
      Sepharose resins in the presence of three different salts. The predictive power
      of these models was validated using a set of test proteins that were not used in
      the generation of these models. Interpretation of the models revealed that
      particular trends for proteins and salts could be captured using QSRR techniques.

PMID- 14570212
TI  - Performance study of diffusive gradients in thin films for 55 elements.
AB  - The technique of diffusive gradients in thin films (DGT) is a fairly new and
      useful tool for in situ measurements of labile metal ions in water. The
      applicability of DGTs was investigated by comparing independently determined or
      estimated diffusion coefficients with DGT effective diffusion coefficients
      (D(DGT)) for 55 elements. The DGTs were exposed at a controlled fluid velocity of
      0.1 m s(-1) and a concentration of 1 ng mL(-1) at four pH levels between 4.7 and
      6.0, and the D(DGT) values were determined from the uptake by the sampler. The
      measured D(DGT) values for the elements Co, Ni, Cu, Zn, Cd, Pb, Al, Mn, and Ga
      were close to previously published values with some deviations for Pb and Zn. The
      uptake of V, Cr, Fe, U, Mo, Ti, Ba, and Sr varied with pH, and there were some
      experimental problems that require further investigations. A novel set of D(DGT)
      values for the lanthanides (La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Tb,
      Yb, Lu, Y) was established. The D(DGT) values for these were about 10-15% lower
      than for free ions in water and indicate that diffusion coefficients of metal
      ions in the agarose polyacrylamide diffusive hydrogel are 10-15% lower than in
      water. The high consistency of the data for the lanthanides establishes these
      elements as new performance test metals for the DGT sampler. The accumulation of
      the elements Li, Na, K, Rb, Mg, Ca, B, Tl, P, S, As, Bi, Se, Si, Sn, Sb, Te, Zr,
      Nb, Hf, Ta, W, Th, and Ag was low (D(DGT) lower than 10% of theoretical values).
      A more efficient elution procedure using concentrated nitric acid for the
      absorbent gel was established, with elution efficiencies between 95 and 100% for
      most metals. For deployment times of 24 h, detection limits from 0.001 to 1 ng
      mL(-1) were achieved with moderate precautions to prevent contamination.

PMID- 14570213
TI  - Microfluidic device for single-cell analysis.
AB  - We have developed a novel microfluidic device constructed from
      poly(dimethylsiloxane) using multilayer soft lithography technology for the
      analysis of single cells. The microfluidic network enables the passive and gentle
      separation of a single cell from the bulk cell suspension, and integrated valves
      and pumps enable the precise delivery of nanoliter volumes of reagents to that
      cell. Various applications are demonstrated, including cell viability assays,
      ionophore-mediated intracellular Ca2+ flux measurements, and multistep receptor
      mediated Ca2+ measurements. These assays, and others, are achieved with
      significant improvements in reagent consumption, analysis time, and temporal
      resolution over macroscale alternatives.

PMID- 14570214
TI  - Use of a water-soluble fullerene derivative as precipitating reagent and matrix
      assisted laser desorption/ionization matrix to selectively detect charged species
      in aqueous solutions.
AB  - A starlike water-soluble fullerene derivative, hexa(sulfonbutyl)fullerene
      (C60[(CH2)4SO3-]6; HSBF), consisting of a C60 cage covalently bonded with six
      negatively charged sulfonate arms, was synthesized and used to selectively
      precipitate positively charged surfactants, amino acids, peptides, and proteins.
      The affinity of HSBF to the analytes depends on the charge, structure, and
      hydrophobic characteristics of the analytes. The ion pair precipitate was easily
      removed from the solution by centrifugation. After washing, the precipitate was
      redissolved in the solvent or buffer solution and the analyte was characterized
      by laser desorption ionization-time-of-flight mass spectrometry (LD-TOF). HSBF
      shows strong optical absorbance in the UV range, so no additional organic matrix
      was required to conduct LD-TOF analysis of small analytes. For the solution that
      contained five quaternary amines differing only in alkyl chain length, HSBF
      exhibits the highest affinity to the amine with the longest alkyl chain. Only the
      arginine signal was detected from the solution that contained 14 amino acids. The
      peptides with arginine as the end groups interacted most strongly with HSBF and
      could be selectively precipitated from a solution of a mixture of five peptides.
      The signals associated with a trace amount of charged peptides derived from the
      digestion of proteins by trypsin were greatly enhanced after concentration with
      HSBF. Among eight proteins in the sample solution, insulin had the strongest
      affinity to the HSBF and exhibited the strongest signal on the matrix-assisted
      laser desorption/ionization mass spectrum.

PMID- 14570215
TI  - High-efficiency on-line solid-phase extraction coupling to 15-150-microm-i.d.
      column liquid chromatography for proteomic analysis.
AB  - The ability to manipulate and effectively utilize small proteomic samples is
      important for analyses using liquid chromatography (LC) in combination with mass
      spectrometry (MS) and becomes more challenging for very low flow rates due to
      extra column volume effects on separation quality. Here we report on the use of
      commercial switching valves (150-microm channels) for implementing the on-line
      coupling of capillary LC columns operated at 10,000 psi with relatively large
      solid-phase extraction (SPE) columns. With the use of optimized column
      connections, switching modes, and SPE column dimensions, high-efficiency on-line
      SPE-capillary and nanoscale LC separations were obtained demonstrating peak
      capacities of approximately 1000 for capillaries having inner diameters between
      15 and 150 microm. The on-line coupled SPE columns increased the sample
      processing capacity by approximately 400-fold for sample solution volume and
      approximately 10-fold for sample mass. The proteomic applications of this on-line
      SPE-capillary LC system were evaluated for analysis of both soluble and membrane
      protein tryptic digests. Using an ion trap tandem MS it was typically feasible to
      identify 1100-1500 unique peptides in a 5-h analysis. Peptides extracted from the
      SPE column and then eluted from the LC column covered a
      hydrophilicity/hydrophobicity range that included an estimated approximately 98%
      of all tryptic peptides. The SPE-capillary LC implementation also facilitates
      automation and enables use of both disposable SPE columns and electrospray
      emitters, providing a robust basis for automated proteomic analyses.

PMID- 14570216
TI  - Solid-phase microextraction liquid chromatography/tandem mass spectrometry to
      determine postharvest fungicides in fruits.
AB  - A method to determine five postharvest fungicides (dichloran, flutriafol, o
      phenylphenol, prochloraz, tolclofos methyl) in fruits (cherries, lemons, oranges,
      peaches) has been developed using solid-phase microextraction (SPME) coupled to
      liquid chromatography (LC) with photodiode array (DAD), mass spectrometry (MS),
      or tandem mass spectrometry (MS/MS) with ion trap detection. Extraction involved
      sample homogenization with an acetone/water solution (5:1), filtration, and
      acetone evaporation prior to fiber extraction. The pesticides were isolated with
      a fused-silica fiber coated with 50-microm Carbowax/template resin. The effects
      of pH, ion strength, sample volume, and extraction time were investigated, and
      their impact on the SPME-LC/MS was studied. Dynamic and static modes of
      desorption were compared and the variables affecting desorption processes in SPME
      LC optimized. Static desorption provided the best recoveries and peak shapes.
      Recoveries at the limit of quantification (LOQ) levels were between 10% for
      prochloraz and 60% for o-phenylphenol, with relative standard deviations from
      13.6% for prochloraz to 3.1% for o-phenylphenol. The versatility of the method
      was also exhibited by its excellent linearity in the concentration intervals
      between 0.0005 and 5 mg kg(-1) for dichloran and 0.01-10 mg kg(-1) for tolclofos
      methyl and prochloraz. LOQs ranged from 0.25 to 1 microg g(-1) using DAD, from
      0.002 to 0.01 microg g(-1) using LC/MS, and from 0.0005 to 0.01 to microg g(-1)
      using LC/MS/MS. LOQs obtained in the present study using LC/MS and LC/MS/MS are
      lower than maximum residue limits established for all the fungicides in any
      matrix studied. The method enables to determine polar pesticides at low-microgram
      per gram levels in fruits.

PMID- 14570217
TI  - Total internal reflection fluorescence-correlation spectroscopy study of
      molecular transport in thin sol-gel films.
AB  - Total internal reflection fluorescence correlation spectroscopy is used to
      measure mass transport rates through thin sol-gel films. Fluctuations in the
      fluorescence signal derive from molecular statistics due to the small number
      (approximately 1000) of rhodamine 6G dye molecules in the observation region.
      Autocorrelation of the fluctuating signal is fit to a model describing diffusion
      in the evanescent wave excitation. Silica sol-gel films were prepared by dip
      coating 27-nm porous silica particles, which were synthesized by a base-catalyzed
      sol-gel method, onto microscope slides. The measured diffusivities ranged from 1
      to 2 orders of magnitude slower than free diffusion and decreased with increasing
      number of dips used to prepare the film. Scanning electron microscopy (SEM) was
      used to examine the film structure and showed that increasing the number of dips
      produced more uniform and well-ordered films. To determine what role the dip
      coating process plays in inducing order, deposited films were further dipped into
      ethanol containing no particles. These films were annealed by this process and
      become more ordered, as determined by SEM, and show a corresponding reduction in
      the molecular diffusivity.

PMID- 14570218
TI  - Gas adsorption gates based on ultrathin composite polymer films.
AB  - High surface area alumina coatings were prepared on surface acoustic wave (SAW)
      mass balances. These coatings were fabricated by anodic etching of evaporated
      aluminum films. The coatings consisted of roughly collinear pores penetrating
      through the monolithic alumina film. The nanoporous (NP) coatings were
      characterized by scanning electron microscopy, and the pore number density and
      diameter were found to be (3.8 +/- 0.5) x 10(3) pores/microm2 and 6.8 +/- 4.8 nm,
      respectively. The mass of volatile organic compounds that adsorbed onto naked and
      chemically modified NP alumina coatings was measured using SAW mass balances and
      compared to the mass absorbed onto SAW devices having planar aluminum coatings.
      Thirty-four times more heptane adsorbed to the naked NP coating than to the
      planar coating. The mass loading response was also measured after modification
      with organic thin films (3-12 nm thick) that spanned the pores of the NP coating.
      These organic thin films were composed of sixth-generation, amine-terminated
      poly(amido amine) dendrimers and poly(maleic anhydride)-c-poly(methyl vinyl
      ether) (Gantrez). The key result of this study is that these organic thin films
      modulate adsorption of VOCs onto the pore walls of the NP alumina. Specifically,
      a single 3-nm-thick monolayer of the dendrimer reduces permeability of the VOCs
      by approximately 17%, whereas a 12-nm-thick G6-NH2/Gantrez composite reduces
      permeability by 100%. Thus, the polymer composite acts as a nonselective gate
      that controls access of VOCs to the underlying surface area of the pores.

PMID- 14570219
TI  - A perfect smoother.
AB  - The well-known and popular Savitzky-Golay filter has several disadvantages. A
      very attractive alternative is a smoother based on penalized least squares,
      extending ideas presented by Whittaker 80 years ago. This smoother is extremely
      fast, gives continuous control over smoothness, interpolates automatically, and
      allows fast leave-one-out cross-validation. It can be programmed in a few lines
      of Matlab code. Theory, implementation, and applications are presented.

PMID- 14570220
TI  - Miniaturized tris(2,2'-bipyridyl)ruthenium(II) electrochemiluminescence detection
      cell for capillary electrophoresis and flow injection analysis.
AB  - The design and performance of a miniaturized chip-type tris(2,2'
      bipyridyl)ruthenium(II) [Ru(bpy)3(2+)] electrochemiluminescence (ECL) detection
      cell suitable for both capillary electrophoresis (CE) and flow injection (FI)
      analysis are described. The cell was fabricated from two pieces of glass (20 x 15
      x 1.7 mm), and the 0.5-mm-diameter platinum disk was used as working electrode
      held at +1.15 V (vs silver wire quasi-reference), the stainless steel guide
      tubing as counter electrode, and the silver wire as quasi-reference electrode.
      The performance traits of the cell in both CE and FI modes were evaluated using
      tripropylamine, proline, and oxalate and compared favorably to those reported for
      CE and FI detection cells. The advantages of versatility, sensitivity, and
      accuracy make the device attractive for the routine analysis of amine-containing
      species or oxalate by CE and FI with Ru(bpy)3(2+) ECL detection.

PMID- 14570221
TI  - Portable high-voltage power supply and electrochemical detection circuits for
      microchip capillary electrophoresis.
AB  - Miniaturized, battery-powered, high-voltage power supply, electrochemical (EC)
      detection, and interface circuits designed for microchip capillary
      electrophoresis (CE) are described. The dual source CE power supply provides +/-
      1 kVDC at 380 microA and can operate continuously for 15 h without recharging.
      The amperometric EC detection circuit provides electrode potentials of +/-2 VDC
      and gains of 1, 10, and 100 nA/V. The CE power supply power is connected to the
      microchip through an interface circuit consisting of two miniature relays,
      diodes, and resistors. The microchip has equal length buffer and separation
      channels. This geometry allows the microchip to be controlled from only two
      reservoirs using fixed dc sources while providing a consistent and stable sample
      injection volume. The interface circuit also maintains the detection reservoir at
      ground potential and allows channel currents to be measured likewise. Data are
      recorded, and the circuits are controlled by a National Instruments signal
      interface card and software installed in a notebook computer. The combined size
      (4 in. x 6 in. x 1 in.) and weight (0.35 kg) of the circuits make them ideal for
      lab-on-a-chip applications. The circuits were tested electrically, by performing
      separations of dopamine and catechol EC and by laser-induced fluorescence
      visualization.

PMID- 14570222
TI  - Near-infrared spectrometry of abdominal aortic aneurysm in the ApoE-/- mouse.
AB  - Abdominal aortic aneurysms (AAAs) occur in 5-7% of people over age 60 in the
      United States. Early intervention in the disease process could have a significant
      impact on the incidence of complications and on patient survival, but identifying
      incipient aneurysms can be difficult. ApoE knockout mice develop AAAs following
      infusion of angiotensin II (AngII) by osmotic minipump into the subcutaneous
      space of mice at doses ranging from 500 to 1000 ng kg(-1) min(-1) for 7-28 days.
      These mice are used as models of AAA development. This study tested the
      hypothesis that near-IR spectrometry and PCR can determine AngII dose (SEE = 26
      ng kg(-1) min(-1), SEP = 37 ng kg(-1) min(-1), r2 = 0.99) and collagen/elastin
      (C/E) ratio (SEE = 0.38, SEP = 0.39, r2 = 0.85) in mouse aortas.

PMID- 14570223
TI  - CE in a nonuniform capillary modulated by a cylindrical insert, and zone
      narrowing effects during sample injection.
AB  - The electrophoretic behavior of an analyte in a capillary consisting of two parts
      of different cross section has been investigated. Modulation of the cross
      sectional area of the separation channel has been achieved by inserting a
      cylindrical fiber different distances into the capillary. It was shown that the
      zone injected into the capillary part with smaller cross section could be moved
      using electromigration into the wider part of the capillary with zone
      compression. As we observed, the zone narrowed longitudinally in the wide part of
      the capillary in accordance with the ratio of the electric field strength in the
      two parts of the capillary. The concentration of plug introduced into the
      capillary by electroinjection can be increased by use of low-conductivity sample
      buffer. Efficient introduction of extracted analytes desorbed from an SPME fiber
      to the separation channel was achieved using this approach. Thermoinduced effects
      caused by temperature increase in the narrow part of the capillary and their
      influence on sample stacking are analyzed. Possible applications of the effect
      observed to the sample introduction optimization are also discussed in this
      study.

PMID- 14570225
TI  - Comments on "A microfabricated thermal field-flow fractionation system".

PMID- 14570224
TI  - Reproducibility in fabrication and analytical performance of polyaniline-coated
      nanoelectrospray emitters.
AB  - Nanoelectrospray ionization mass spectrometry is an ideal technique for analysis
      of biomolecules when sample quantities are limited. With the use of this
      technique, 1-2 microL of sample can be electrosprayed for long time periods
      (hours) because of the low flow rate (nanoliters per minute) attainable. However,
      the long-term durability of such emitters has been an impediment to the routine
      use of nanoelectrospray. The development of longer-lasting nanoelectrospray
      emitters has often resulted in increasingly complex and tedious fabrication
      processes. Furthermore, an easily produced, reproducible, and durable
      nanoelectrospray emitter is the ultimately desired goal. Here, the
      reproducibility of the inner diameters and geometry for nanoelectrospray emitter
      glass substrates is assessed using scanning electron microscopy (SEM). The
      results indicate that provided that glass pulling parameters remain constant,
      reproducible inner diameters can be produced from glass capillary tubing within
      the same batch; however, there are interbatch differences. In addition, SEM
      revealed reproducible taper geometry could also be obtained. Borosilicate and
      fused-silica nanoelectrospray emitters produced by these protocols were then
      coated with polyaniline, and their analytical figures of merit were determined
      using a triple quadrupole mass analyzer. Over a 1-h run, polyaniline-coated
      emitters showed fairly stable signal with coefficients of variation ranging from
      8.92 to 27.6%. Single-scan detection limits below 1 amol were achieved for
      polyaniline-coated fused-silica emitters for flow rates averaging <10 nL/min.
      Linear mass spectrometric response with solution concentration was observed for
      the polyaniline-coated emitters over the range 10 nM-10 microM, with coefficients
      of variation ranging from 1.44 to 7.26%. This indicates that when nanelectrospray
      emitter inner diameters are made reproducibly, it is possible to achieve linear
      quantitative response for nanoelectrospray.

PMID- 14570226
TI  - The American Cancer Society guide for nutrition and physical activity for cancer
      survivors: a call to action for clinical investigators.

PMID- 14570227
TI  - Nutrition and physical activity during and after cancer treatment: an American
      Cancer Society guide for informed choices.
AB  - Cancer survivors are often highly motivated to seek information about food
      choices, physical activity, dietary supplement use, and complementary nutritional
      therapies to improve their treatment outcomes, quality of life, and survival. To
      address these concerns, the American Cancer Society (ACS) convened a group of
      experts in nutrition, physical activity, and cancer to evaluate the scientific
      evidence and best clinical practices related to optimal nutrition and physical
      activity after the diagnosis of cancer. This report summarizes their findings and
      is intended to present health care providers with the best possible information
      on which to help cancer survivors and their families make informed choices
      related to nutrition and physical activity. The report discusses nutrition and
      physical activity issues during the phases of cancer treatment and recovery,
      living after recovery from treatment, and living with advanced cancer; selected
      nutritional and physical activity issues such as body weight, food choices, and
      complementary and alternative nutritional options; and selected issues related to
      breast, colorectal, lung, prostate, head and neck, and upper gastrointestinal
      cancers. In addition, handouts containing commonly asked questions and answers
      and a resource list are provided for survivors and families. Tables that grade
      the scientific evidence for benefit versus harm related to nutrition and physical
      activity for breast, colorectal, lung, and prostate cancers are also included for
      this growing body of knowledge to provide guidance for informed decision making
      and to identify areas for future research.

PMID- 14570228
TI  - Keratinocyte carcinoma.
AB  - Keratinocyte carcinoma is by far the most common cancer in the United States.
      Basal cell carcinomas and squamous cell carcinomas account for approximately 80%
      and 20% of cases of KC, respectively. The term nonmelanoma skin cancer is
      commonly used to refer to squamous cell carcinomas and basal cell carcinomas;
      however, other types of nonmelanoma skin cancer, such as adnexal tumors and
      sarcomas, are less common and differ in their cell type, behavior, and
      epidemiologic features from KC. Primary care clinicians are well positioned to
      diagnose KC and to educate patients about preventive measures such as sun
      protection and self-examination. Here we review epidemiologic data and strategies
      for prevention, diagnosis, and clinical management of KC.

PMID- 14570229
TI  - Patient Pages. Answers to questions often asked by cancer survivors about
      nutrition and physical activity.

PMID- 14570230
TI  - Deaths: final data for 2001.
AB  - OBJECTIVES: This report presents final 2001 data on U.S. deaths and death rates
      according to demographic and medical characteristics such as age, sex, Hispanic
      origin, race, marital status, educational attainment, injury at work, State of
      residence, and cause of death. Trends and patterns in general mortality, life
      expectancy, and infant and maternal mortality are also described. A previous
      report presented preliminary mortality data for 2001. METHODS: In 2001 a total of
      2,416,425 deaths were reported in the United States. This report presents
      descriptive tabulations of information reported on the death certificates.
      Funeral directors, attending physicians, medical examiners, and coroners complete
      death certificates. Original records are filed in the State registration offices.
      Statistical information is compiled into a national database through the Vital
      Statistics Cooperative Program of the National Center for Health Statistics
      (NCHS), Centers for Disease Control and Prevention. Causes of death are processed
      in accordance with the International Classification of Diseases Tenth Revision
      (ICD-10). RESULTS: The age-adjusted death rate for the United States in 2001 was
      854.5 deaths per 100,000 standard population, representing a decrease of 1.7
      percent from the 2000 rate and a record low historical figure. Life expectancy at
      birth rose by 0.2 years to a record high of 77.2 years. Considering all deaths,
      age-specific death rates rose only for those 25-44 years, and declined for a
      number of age groups including those under 1 year, 5-14 years, 55-64 years, 65-74
      years, 75-84 years, and 85 years and over. The 15 leading causes of death in 2001
      remained the same as in 2000. Heart disease and cancer continued to be the
      leading and second leading causes of death, together accounting for over half of
      all deaths. Homicide became the 13th leading cause in 2001, rising from the 14th
      leading cause in 2000 as a result of the September 11, 2001, terrorist attacks.
      The infant mortality rate remained at a record low level, declining slightly but
      insignificantly from 6.9 in 2000 to 6.8 in 2001. CONCLUSIONS: Generally,
      mortality patterns in 2001 were consistent with long-term trends. Life expectancy
      in 2001 increased again to a new record level. The age-adjusted death rate
      declined to a record low historical figure. Although statistically unchanged from
      2000, the trend in infant mortality has shown a steady, although slowing,
      decline. The declining trend in the homicide death rate was reversed primarily as
      a result of the September 11, 2001, terrorist attacks.

PMID- 14570231
TI  - Developmental differences in the immortalization of lung fibroblasts by
      telomerase.
AB  - The role of ambient (21%) and physiological oxygen (2-5%) in the immortalization
      of fetal vs. adult human lung fibroblasts was examined. Growth in low oxygen and
      antioxidants extended the lifespan of both fetal and adult strains. As the
      ectopic expression of telomerase could immortalize adult lung fibroblasts
      cultured in ambient oxygen, the lifespan-shortening effects of 21% oxygen must
      have been largely limited to telomeres. By contrast, fetal lung fibroblasts could
      not be immortalized in ambient oxygen in spite of telomere elongation by
      telomerase, suggesting more widespread oxidative damage. The long-term culture
      requirements for the immortalization of WI-38 fetal lung fibroblasts included
      supplementation with N-(tert) butyl hydroxylamine, dexamethasone, zinc and
      vitamin B12, in addition to growth in physiological oxygen. The mechanisms
      regulating telomere shortening remain controversial. The present results suggest
      that both end-replication and oxidative damage events contribute to telomere
      shortening in lung fibroblasts in vitro. These observations emphasize the need
      for better analytical techniques to distinguish whether the correlation of short
      telomeres with disease and mortality in humans reflects the consequences of
      increased proliferation, telomere shortening as a result of oxidative damage or
      some combination of these processes.

PMID- 14570232
TI  - Tumour necrosis factor-alpha- vs. growth factor deprivation-promoted cell death:
      distinct converging pathways.
AB  - Perturbations of neuronal physiological homeostasis are likely to underscore
      neuronal demise/impairments that are reportedly associated with aging of the
      central nervous system and age-related neurodegenerative diseases such as
      Alzheimer's disease (AD). A number of age- and/or disease-associated neurotoxic
      events has been described. These include abnormally modified proteins such as
      beta amyloid and hyper-phosphorylated Tau, cytokines such as tumour necrosis
      factor-alpha (TNFalpha), high levels of free radicals conducive to oxidative
      stress, and impaired/decreased neuronal trophic support by neurotrophic factors.
      Overall, it could be argued that toxic events in the aged brain are either
      active, such as those due to a direct action of cytokines, or passive, such as
      those due to lack of growth factor support. It is therefore conceivable that
      cellular responses to such diverse toxic stimuli are different, suggesting that
      interventions should be targeted accordingly. In order to begin answering this
      question, we determined in PC12 cells the time course of activity, in response to
      TNFalpha (active) or growth factor withdrawal (passive), of protein kinase c-zeta
      (PKCzeta), nuclear factor kappa B (NFkappaB), caspases 3 and 8, and poly (ADP
      ribose) polymerase (PARP), key signal transduction elements associated with
      modulation of cell death/survival in PC12 cells. We found that the overall
      activity of PKCzeta, NFkappaB and caspase 8 was significantly different depending
      on the apoptotic initiator. The pattern of caspase 3 and PARP activity, however,
      was not statistically different between serum-free- and TNFalpha-induced cell
      death conditions. This suggests that two distinct cell responses are elicited
      that converge at caspase 3, which then induces downstream events involved in the
      execution of a common apoptotic programme. These results contribute to the aim of
      differentially targeting neuronal death in the aged brain (characterized by
      neurotrophic factor impairments) or in the diseased brain (e.g. AD, characterized
      by elevated levels of pro-inflammatory cytokines).

PMID- 14570233
TI  - Delayed behavioural aging and altered mortality in Drosophila beta integrin
      mutants.
AB  - The genetic basis for aging is being intensely investigated in a variety of model
      systems. Much of the focus in Drosophila has been on the molecular-genetic
      determinants of lifespan, whereas the molecular-genetic basis for age-related
      functional declines has been less vigorously explored. We evaluated behavioural
      aging and lifespan in flies harbouring loss-of-function mutations in myospheroid,
      the gene that encodes betaPS, a beta integrin. Integrins are adhesion molecules
      that regulate a number of cellular processes and developmental events. Their role
      in aging, however, has received limited attention. We report here that age
      related declines in locomotor activity are ameliorated and that mean lifespan is
      increased in myospheroid mutants. The delayed functional senescence and altered
      mortality in myospheroid flies are independent of changes in body size,
      reproduction or stress resistance. Our data indicate that functional senescence
      and age-dependent mortality are influenced by beta integrins in Drosophila.

PMID- 14570234
TI  - Age-related changes in the metabolism and body composition of three dog breeds
      and their relationship to life expectancy.
AB  - We measured body composition and resting metabolic rates (RMR) of three dog
      breeds (Papillons, mean body mass 3.0 kg (n = 35), Labrador retrievers, mean body
      mass 29.8 kg (n = 35) and Great Danes, mean body mass 62.8 kg (n = 35)) that
      varied between 0.6 and 14.3 years of age. In Papillons, lean body mass (LBM)
      increased with age but fat mass (FBM) was constant; in Labradors, both LBM and
      FBM were constant with age, and in Great Danes, FBM increased with age but LBM
      was constant. FBM averaged 14.8% and 15.7% of body mass in Papillons and
      Labradors, respectively. Great Danes were leaner and averaged only 10.5% FBM.
      Pooling the data for all individuals, the RMR was significantly and positively
      associated with LBM and FBM and negatively associated with age. Once these
      factors had been taken into account there was still a significant breed effect on
      RMR, which was significantly lower in Labradors than in the other two breeds.
      Using the predictive multiple regression equation for RMR and the temporal trends
      in body composition, we modelled the expenditure of energy (at rest) over the
      first 8 years of life, and over the entire lifespan for each breed. Over the
      first 8 years of life the average expenditure of energy per kg LBM were 0.985,
      0.675 and 0.662 GJ for Papillons, Labradors and Great Danes, respectively. This
      energy expenditure was almost 60% greater for the smallest compared with the
      largest breed. On average, however, the life expectancy for the smallest breed
      was a further 6 years (i.e. 14 years in total), whereas for the largest breed it
      was only another 6 months (i.e. 8.5 years in total). Total lifetime expenditure
      of energy at rest per kg LBM averaged 1.584, 0.918 and 0.691 GJ for Papillons,
      Labradors and Great Danes, respectively. In Labradors, total daily energy
      expenditure, measured by the doubly labelled water method in eight animals, was
      only 16% greater than the observed RMR. High energy expenditure in dogs appears
      positively linked to increased life expectancy, contrary to the finding across
      mammal species and within exotherms, yet resembling observations in other intra
      specific studies. These contrasting correlations suggest that metabolism is
      affecting life expectancy in different ways at these different levels of enquiry.

PMID- 14570235
TI  - Mitochondrial oxidative stress causes chromosomal instability of mouse embryonic
      fibroblasts.
AB  - Reactive oxygen species are an inevitable by-product of mitochondrial
      respiration. It has been estimated that between 0.4 and 4% of molecular oxygen is
      converted to the radical superoxide (O2*-) and this level is significantly
      influenced by the functional status of the mitochondria. It is well established
      that exogenous oxidative stress and high doses of mitochondrial poisons such as
      paraquat and carbonyl cyanide 4 (trifluoromethoxy) phenylhydrazone (FCCP) can
      lead to genomic instability. In this report we show for the first time that
      endogenous mitochondrial oxidative stress in standard cell culture conditions
      results in nuclear genomic instability in primary mouse embryonic fibroblasts
      (MEFs). We show that lack of mitochondrial superoxide dismutase in MEFs leads to
      a severe increase of double strand breaks, end-to-end fusions, chromosomal
      translocations, and loss of cell viability and proliferative capacity. Our
      results predict that endogenous mitochondrial oxidative stress can induce genomic
      instability, and therefore may have a profound effect in cancer and aging.

PMID- 14570236
TI  - Modified binaural pitch-matching test for the assessment of diplacusis.
AB  - Diplacusis is defined as the phenomenon of hearing the same tone at different
      pitches in the two ears. Although binaural pitch-matching using method-of
      adjustment has been employed in most studies, it is sometimes hard for subjects
      with impaired hearing to judge 'equal pitch' as one frequency. To resolve this
      problem. a modified pitch-matching test, in which the relation of pitch sensation
      between the two ears was assessed as a matched frequency 'range' using the
      randomized maximum likelihood sequential procedure, was developed. Eight subjects
      with unilaterally impaired hearing, as well as eight normal subjects, were
      examined to evaluate this new test procedure. In the present method, matched
      frequency is assessed as a frequency range, in which subjects cannot judge
      whether the pitch of the signal in one ear is higher or lower than that in the
      opposite ear. This method appeared to be useful for assessing the characteristics
      of diplacusis in subjects with impaired hearing as well as in normal subjects.

PMID- 14570237
TI  - Assessment of auditory processing in 6-year-old language-impaired children.
AB  - The performance of a group of twenty 6-year-old children with specific language
      impairment (SLI) on several behavioural auditory tests was compared to that of a
      group of twenty age-matched control children. The auditory test battery used in
      this study consisted of the following tests: a speech-in-noise test, a filtered
      speech test, a binaural fusion test, a frequency pattern test, a duration pattern
      test, a temporal integration test, an auditory word discrimination test, an
      auditory synthesis test, an auditory closure test and a number recall test. Our
      results show that the SLI children obtained scores on almost all tests that were
      significantly lower than those of the control group. Many of the basic auditory
      processing measures in our test battery correlated significantly with receptive
      and language scores, suggesting a (causal) relationship between auditory
      processing and language proficiency. Results from discriminant function analyses
      do not warrant deleting one or more tests from the test battery yet (with the
      exception of the auditory synthesis test and the temporal integration test, for
      which we did not find significant group effects). At present, we are conducting
      experiments with older (SLI and control) children and adults to find whether the
      significant performance deficits of the SLI children are also found in older SLI
      children, and to determine the influence of maturational effects on these
      auditory tests.

PMID- 14570238
TI  - King-Kopetzky syndrome in the light of an ecological conceptual framework.
AB  - The principal symptom of subjects suffering from King-Kopetzky syndrome is a
      perceived difficulty in recognizing and understanding speech in noisy
      backgrounds. For some patients, minor disturbances in auditory function, e.g. a
      deteriorated signal-to-noise ratio for speech, can be demonstrated; for others,
      all measurements of hearing are normal. A conceptual framework developed for the
      analysis of communication disorders is applied to King-Kopetzky syndrome in the
      present article. The usefulness of the framework is evaluated, and an extended
      system for the analysis of King-Kopetzky syndrome patients is suggested. It is
      emphasized that changes in demands resulting from external conditions and altered
      perception and evaluation of the conditions may generate the symptoms. A change
      in the subjects' desired self-image (preferendum) and a change in social role,
      new, unfamiliar vocabulary, as well as minor dysfunctions in peripheral and
      central auditory processing, might generate the characteristic features of the
      syndrome. The framework is related to the current literature, and arguments for
      the usefulness of the framework in the planning of support and rehabilitation are
      presented. Several new questions are generated for further analysis of King
      Kopetzky syndrome.

PMID- 14570239
TI  - Impact on hearing aid targets of measuring thresholds in dB HL versus dB SPL.
AB  - Audiometric measurements are traditionally made in dB HL, which by definition are
      specified relative to the sound pressure level (SPL) in a coupler. Real-ear dB
      SPL is then estimated by applying an average ear transform to the coupler value.
      However, individual variation in ear canal acoustics and variations in transducer
      placement strongly influence the dB SPL of signals arriving at the eardrum. In
      this paper, data from 1814 ears are presented, showing that the distribution of
      eardrum dB SPL for a fixed signal level varies across ears and across frequency
      by as much as 40 dB. The impact of this variance upon hearing aid targets
      computed with the NAL-NL1 fitting algorithm is examined by comparing the targets
      obtained from using an average transform with those obtained when audiometric
      data in dB SPL are obtained by applying individually measured real-ear-to-coupler
      difference (RECD) values to dB HL thresholds. The impact can be considerable.

PMID- 14570240
TI  - Normative values for tympanometry in 4-5-year-old children.
AB  - The objective of this study was to determine normative values for tympanometric
      variables for 4-5-year-old children. Tympanometry was performed at a pre
      scheduled visit at the age of 49-68 months on children recruited to a follow-up
      visit in a vaccine efficacy trial (n=756 children). Tympanograms obtained
      successfully from healthy ears were analysed. At the time of the visit, mean
      static acoustical admittance (SAA) was 0.52 cm3, mean tympanometric peak pressure
      (TPP) was -48 daPa, and mean tympanometric width (TW) was 101. Compared to
      results obtained for the same study population at 24 months of age, the SAA had
      increased significantly with age, while the values for TPP and TW had decreased
      with age. A history of previous tympanostomy tubes increased the admittance of
      the tympanic membrane by producing atrophic scars. Thus, the tympanograms
      obtained from ears with previous tubes were considerably higher and narrower
      (high SAA and low TW). In conclusion, this study further emphasizes the need for
      age-specific normative values for interpretation of SAA and TW.

PMID- 14570241
TI  - Combination of derived non-linear and linear methods to increase the
      reproducibility of transiently evoked otoacoustic emissions.
AB  - This paper proposes a segmented average method that combines the derived non
      linear response (DNLR) and linear-averaging methods to increase the
      reproducibility of transiently evoked otoacoustic emissions (TEOAEs). In this
      method, the DNLR method is used at the 2.5-P-ms segment of each TEOAE signal, and
      the linear-averaging method is used from P to 20 ms. This exploits the reduced
      artefact advantage of the DNLR method and the high-reproducibility advantage of
      the linear-averaging method. To evaluate the performance of the proposed method,
      26 normal ears were tested, with P selected as 8 ms. Each TEOAE signal obtained
      was decomposed into three scales using the discrete wavelet transform. Then the
      similarities and differences between the signals obtained with this method and
      with the DNLR method were assessed. The results show that the average
      reproducibility of the TEOAE signals increases from 78.1%, to 88.7% when applying
      the proposed method.

PMID- 14570242
TI  - TEOAE recording protocols revised: data from adult subjects.
AB  - The objective of this study was the experimental re-evaluation of the current
      clinical transiently evoked otoacoustic emission (TEOAE) protocols, based on
      linear and non-linear protocol paradigms from a population of 42 adult subjects
      serving as a normative database. The linear and non-linear TEOAE responses were
      elicited by clicks with average intensities of 72 and 84 dB p.e. SPL
      respectively. An initial comparison between non-processed non-linear and linear
      recordings, at early recording segments from 3.2 to 5.2 ms, showed that the
      responses had highly similar contours and no statistically significant mean
      differences. The stimulus-induced artefact in the linear TEOAE responses was
      suppressed by post-processing the data with a window function (3.8-13.8 ms) and
      by a high-pass filter at 830 Hz. A repeated-measures model was used to evaluate
      the differences between post-processed linear and non-linear responses across
      clinical variables of interest (such as TEOAE response, noise, correlation, and
      signal-to-noise ratios (SNRs) at 1.0-5.0 kHz). The data indicated that the linear
      recordings demonstrate significantly lower levels of noise (and thus superior
      SNRs) and higher values of reproducibility. Normative adult scoring criteria were
      calculated from free distribution tolerance intervals for the TEOAE correlation
      and the SNRs at 2.0 and 3.0 kHz.

PMID- 14570243
TI  - Immediate and short-term reliability of distortion-product otoacoustic emissions.
AB  - This study assessed the test-retest reliability of distortion-product otoacoustic
      emissions (DPOAEs) at four frequencies (550, 1000, 2000 and 4000 Hz) over three
      time intervals. The time intervals were: (1) immediate test-retest reliability,
      in which the retest followed the test without any delay or repositioning of the
      probe tip; (2) very short-term test-retest reliability, in which the retest
      followed a 10-20-min break and involved removal and re-insertion of the probe
      tip; and (3) short-term test-retest reliability, in which the retest was
      conducted 5-10 days after the test. Fifty normal-hearing women were tested with a
      commercially available system for measuring DPOAEs (Grason-Stadler, GSI-60),
      which generated primary tones at 65 dB SPL (L1=L2). Standard errors of
      measurement at 550 Hz (approximately 4.6 dB) were nearly twice as large as those
      found for 1000 Hz, 2000 Hz, and 4000 Hz (approximately 2.5 dB). The short-term
      test-retest data suggest that there is a 95% probability that an individual's
      true DPOAE will fall within 5 dB of the obtained distortion product at 1000-4000
      Hz and within 10 dB at 550 Hz. The standard error of measurement of the
      difference was calculated to assess whether two or more DPOAE measurements are
      significantly different (e.g. before versus after administration of an ototoxic
      drug or noise exposure). The data revealed that short-term differences (probe
      removed and subject retested on the same day or on different days) between two
      DPOAEs must exceed approximately 14 dB at 550 Hz and 7 dB at 1000-4000 Hz to be
      statistically significant at the 0.05 level of confidence.

PMID- 14570244
TI  - Gain control from beyond the classical receptive field in primate primary visual
      cortex.
AB  - Gain control is a salient feature of information processing throughout the visual
      system. Heeger (1991, 1992) described a mechanism that could underpin gain
      control in primary visual cortex (V1). According to this model, a neuron's
      response is normalized by dividing its output by the sum of a population of
      neurons, which are selective for orientations covering a broad range. Gain
      control in this scheme is manifested as a change in the semisaturation constant
      (contrast gain) of a V1 neuron. Here we examine how flanking and annular gratings
      of the same or orthogonal orientation to that preferred by a neuron presented
      beyond the receptive field modulate gain in V1 neurons in anesthetized marmosets
      (Callithrix jacchus). To characterize how gain was modulated by surround stimuli,
      the Michaelis-Menten equation was fitted to response versus contrast functions
      obtained under each stimulus condition. The modulation of gain by surround
      stimuli was modelled best as a divisive reduction in response gain. Response gain
      varied with the orientation of surround stimuli, but was reduced most when the
      orientation of a large annular grating beyond the classical receptive field
      matched the preferred orientation of neurons. The strength of surround
      suppression did not vary significantly with retinal eccentricity or laminar
      distribution. In the marmoset, as in macaques (Angelucci et al., 2002a,b), gain
      control over the sort of distances reported here (up to 10 deg) may be mediated
      by feedback from extrastriate areas.

PMID- 14570245
TI  - Structure of glutamate analogs that activate the ON bipolar cell metabotropic
      glutamate receptor in vertebrate retina.
AB  - Although there are many glutamate receptors in the retina, 2-amino-4
      phosphonobutyrate (L-AP4) is an agonist that acts selectively at metabotropic
      glutamate receptors (mGluR6) of ON bipolar cells. We explored the properties of
      agonists that activate this receptor. The effects of various glutamate analogs on
      the b-wave of the electroretinogram (ERG) were used as a measure of their
      activity. Conformational comparisons among agonists suggest that ligands in an
      extended conformation preferentially bind to the ON bipolar synaptic receptor.
      But this property is insufficient to explain the selectivity of mGluR6 because
      some inactive glutamate analogs could also match this extended conformation.
      Comparative molecular field analysis (CoMFA) was used to compare the
      electrostatic and steric potentials of agonists with their action at the ON
      bipolar synapse. Steric potentials beneath a plane defined by the three putative
      binding sites plays a key role in determining agonist activity. The CoMFA model
      was used to predict the activity of glutamate analogs and correlations between
      predicted and measured activity support the model.

PMID- 14570246
TI  - Desensitization of the photoresponse in Limulus ventral photoreceptors by protein
      kinase C precedes rhabdomere disorganization and endocytosis.
AB  - Limulus photoreceptors utilize the phosphoinositide pathway to generate light
      induced single photon events (quantum bumps) that sum to form the depolarizing
      receptor potential. The protein kinase C (PKC) activator, (-)-indolactam V (ILV)
      rapidly desensitizes the light response in Limulus ventral nerve photoreceptors.
      Within 10 min of extracellular application, 100 nM (-)-ILV caused a decrease in
      the mean amplitude of quantum bumps to 38% of control values. PKC activation by (
      )-ILV also causes photosensitive membrane disorganization and endocytosis. To
      investigate whether this precedes desensitization of the electrical response, we
      fixed cells after 10-min incubation with 25 microM (-)-ILV, a concentration
      sufficient to cause a 1000-fold desensitization of the receptor potential. The
      photosensitive microvilli of these photoreceptors remained narrow, densely
      packed, and well organized. Increasing the incubation time to 60 min did,
      however, induce disorganization and swelling of the microvilli and endocytosis of
      the photosensitive membrane, as previously reported. Measurement of membrane
      capacitance did not indicate a significant reduction in membrane area
      accompanying desensitization by (-)-ILV. PKC-induced reduction in light
      sensitivity therefore precedes the detection of ultrastructural changes in the
      rhabdomeral membrane and is not due to a net loss of membrane.

PMID- 14570247
TI  - The identity of metarhodopsin III.
AB  - A fast-scanning dichroic microspectrophotometer was used to trace products of
      rhodopsin photolysis (metarhodopsins I/II/III and later) in structurally intact
      amphibian rod outer segments (ROSs) and metabolically active rods. The instrument
      allows the recording of absorbance spectra with a time resolution better than 1
      s, and to discriminate between products with similar absorbance spectra that
      differ with respect to the orientation of their chromophore in the photoreceptor
      membrane. We demonstrate that metarhodopsin III is in a pH-reversible equilibrium
      with metarhodopsin II and that the metarhodopsin III chromophore is orientated
      with respect to the membrane plane even more strictly than the 11-cis retinal in
      "dark" rhodopsin. This indicates that all-trans retinal in metarhodopsin III is
      still attached to its native binding site on opsin. The kinetic scheme of the
      decay of metarhodopsins is presented in which metarhodopsin III lies in a shunt
      pathway from metarhodopsin II to retinal. Formation of metarhodopsin III was
      detected at bleaches as low as approximately 3%, contrary to previous reports
      that it is not formed at below 10% bleaches. Another product that is spectrally
      similar to metarhodopsin III, termed P440, appears at later stages of photolysis
      as the result of the decay of metarhodopsin II and metarhodopsin III. The
      chromophoric group in P440 is orientated preferentially across the disk membrane.
      The final product(s) in isolated ROS, where the reduction of retinal to retinol
      is blocked, consists of a mixture of a free retinal and retinal possibly attached
      to different binding sites in the membrane. In metabolically active rods the
      later products are quickly converted to retinol. We conclude that metarhodopsin
      III represents a specific conformational state of metarhodopsin where the
      chromophoric binding site is still occupied by all-trans retinal. Hence, the
      formation and decay of metarhodopsin III may be limiting for the rate of
      rhodopsin regeneration and photoreceptor dark adaptation.

PMID- 14570248
TI  - Immunohistochemical analysis of the outer plexiform layer in the nob mouse shows
      no abnormalities.
AB  - In the nob mouse, a mutation in nyctalopin results in a loss of signal
      transmission from photoreceptors to depolarizing bipolar cells (DBCs). We used
      immunohistochemical techniques to assess the expression pattern of proteins found
      at either the photoreceptor terminal or bipolar cell dendrites within the outer
      plexiform layer. We labeled normal and nob retinas with antibodies against
      mGluR6, PKC, G0alpha, bassoon, PSD-95, the alpha1F subunit of voltage-gated
      calcium channels, trkB, and dystrophin. All labeling patterns in nob and normal
      retinas were comparable to those previously reported in mouse retina. Our results
      indicate that the absence of nyctalopin does not disrupt the expression pattern
      of other proteins known to be required for synaptic transmission.

PMID- 14570249
TI  - The effect of retinal growth on the postnatal development and distribution of
      displaced retinal ganglion cells in the retina of the chameleon (squamata).
AB  - Retinal ganglion cells (RGCs) usually increase their dendritic field area with
      postnatal retinal growth. The mechanisms that regulate the postnatal shape of
      dendritic arbors in the growing retina are not well understood. Quantitative
      studies suffer from the difficulty of labeling specific subpopulations of RGCs
      selectively including their dendritic processes. In this study, we labeled
      displaced retinal ganglion cells (DGC) that are known to project to the accessory
      optic system (AOS) in juvenile and adult chameleons by retrograde transport of
      dextran amines. The complete population of DGCs was quantitatively screened for
      the effects of postnatal retinal growth on cell morphology, dendritic field
      coverage, and dendritic arbor size. The adult eye contained 2000 DGCs/retina.
      This number was already present at birth. The smaller size of the hatchling eye
      (approximately 1/3 of the adult size) led to higher densities of DGCs. The
      greatest accumulation of juvenile DGCs (two-fold higher compared to the adult)
      was found in the periphery of the retina where the greatest surface expansion was
      observed. DGC dendritic field areas were adjusted proportionally to this
      expansion in order to maintain a constant dendritic coverage. The increase of
      dendritic fields was mediated by two putative passive mechanisms: First, an
      elongation of individual dendrites similar to previous reports of postnatal RGC
      development in the retina of goldfish and chicks. Second, and more prominent, we
      observed that neighboring dendrites were pulled apart from each other. This
      resulted in a looser spacing of the initially tightly packed dendrites of each
      dendritic arbor. This dispersal of dendrites over a larger area was, due to its
      passive nature, proportional to the increase of the retinal surface and preserved
      a constant dendritic coverage irrespective of the animal's age and eye size.

PMID- 14570251
TI  - Pharmacological analysis of the rat cone electroretinogram.
AB  - The electroretinogram (ERG) of the cone system provides a useful noninvasive
      measure of the activity of the cone pathway. Despite a wide application of the
      cone ERG in the study of rodent models of human hereditary retinal disease, the
      cellular origins of the rat cone ERG have not been well defined. Here, we address
      this issue using a pharmacological approach that has been used previously to
      derive ERG response components. Agents that impair synaptic transmission at well
      defined retinal loci were dissolved in saline and injected into the vitreous of
      adult Sprague-Dawley rats anesthetized with ketamine/xylazine, and cone ERGs were
      recorded approximately 2 h later. Analysis of the resulting waveforms indicated
      that the rat cone ERG includes a relatively small-amplitude component of negative
      polarity that is derived from the activity of cone photoreceptors, and perhaps
      retinal glial (Muller) cells. The cone depolarizing bipolar cell pathway
      contributes a positive potential of large amplitude to the rat cone ERG. In
      comparison, the contribution of hyperpolarizing bipolar cells is of negative
      polarity and of much smaller amplitude. The inner retina contributes a negative
      wave upon which higher frequency oscillations are superimposed. These results
      provide a foundation for interpreting changes in the waveform of the rat cone ERG
      that may be observed following genetic alteration or other experimental
      treatment.

PMID- 14570250
TI  - Evidence for glycine, GABAA, and GABAB receptors on rabbit OFF-alpha ganglion
      cells.
AB  - Inhibitory synaptic transmission via GABA and glycine receptors plays a crucial
      role in shaping the excitatory response of neurons in the retina. Whole-cell
      recordings were obtained from ganglion cells in the intact rabbit eyecup
      preparation to correlate GABA- and glycine-activated currents with the presence
      of their specific receptors on morphologically identified a ganglion cells. Alpha
      ganglion cells were chosen based upon their large somata when viewing the retinal
      surface, and responses to light and dark spots were used to identify OFF-alpha
      ganglion cells. Light responses were abolished by superfusion of Ringer's
      containing cobalt to synaptically isolate the cell by blocking all Ca(2+)
      mediated transmitter release. Pressure pulses of GABA and glycine were delivered
      to an area that encompassed the dendritic field while receptor antagonists were
      applied through superfusion to characterize the direct inhibition onto the
      ganglion cell. Physiological results indicated that OFF-alpha cells did not have
      any GABAc receptor-activated currents, but did express currents mediated by
      ionotropic GABAA receptors and metabotropic GABAB receptors that were blocked by
      their specific antagonists bicuculline and CGP55845, respectively. The amplitudes
      of strychnine-sensitive glycine-activated currents were always larger than the
      currents elicited by GABA. Confocal optical sections of physiologically
      identified, sulforhodamine B-stained cells displayed the localization of glycine
      and GABAA receptor subunit labeling dispersed over the stained dendrites.
      Although scant labeling of GABAB receptors was found on the more distal
      dendrites, the majority of these receptors were congregated at the soma and on
      the proximal dendrites close to the soma. No GABAc receptor immunoreactivity was
      found anywhere on these cells. Therefore, the immunocytochemical results
      corroborated the physiological evidence demonstrating that OFF-alpha ganglion
      cells in the rabbit retina express functional GABAA, GABAB, and glycine
      receptors, but no GABAc receptors.

PMID- 14570252
TI  - Topographies of retinal cone photoreceptors in two Australian marsupials.
AB  - Microspectrophotometry indicates the presence of at least three cone visual
      pigments in two Australian marsupials, the fat-tailed dunnart (Sminthopsis
      crassicaudata) and honey possum (Tarsipes rostratus). Here we have examined the
      distribution of cone types using antisera, JH455 and JH492, that recognize short
      wavelength-sensitive (SWS) and medium-to-long-wavelength-sensitive (M/LWS) cone
      opsins, respectively. SWS cones were concentrated in dorso-temporal retina in the
      dunnart with a shallow decreasing gradient extending to the periphery (2300
      1500/mm2). In the honey possum, SWS cones showed a uniform distribution
      (2700/mm2), except for a slight increase in a narrow peripheral band (3100/mm2).
      In both species, M/LWS cones dominated and their distributions were similar to
      those of retinal ganglion cells: a horizontal streak in the dunnart (31,000
      21,000/mm2) and a shallow mid-ventral to peripheral gradient in the honey possum
      (37,000-26,000/mm2). A low number of cones remained unlabeled when the antisera
      were combined revealing further minority cone population(s). We discuss cone
      distributions in relation to visual capabilities and requirements of the species.

PMID- 14570253
TI  - Strategies of shape representation in macaque visual area V2.
AB  - Contours and surface textures provide powerful cues used in image segmentation
      and the analysis of object shape. To learn more about how the visual system
      extracts and represents these visual cues, we studied the responses of V2 neurons
      in awake, fixating monkeys to complex contour stimuli (angles, intersections,
      arcs, and circles) and texture patterns such as non-Cartesian gratings, along
      with conventional bars and sinusoidal gratings. Substantial proportions of V2
      cells conveyed information about many contour and texture characteristics
      associated with our stimuli, including shape, size, orientation, and spatial
      frequency. However, the cells differed considerably in terms of their degree of
      selectivity for the various stimulus characteristics. On average, V2 cells
      responded better to grating stimuli but were more selective for contour stimuli.
      Metric multidimensional scaling and principal components analysis showed that, as
      a population, V2 cells show strong correlations in how they respond to different
      stimulus types. The first two and five principal components accounted for 69% and
      85% of the overall response variation, respectively, suggesting that the response
      correlations simplified the population representation of shape information with
      relatively little loss of information. Moreover, smaller random subsets of the
      population carried response correlation patterns very similar to the population
      as a whole, indicating that the response correlations were a widespread property
      of V2 cells. Thus, V2 cells extract information about a number of higher order
      shape cues related to contours and surface textures and about similarities among
      many of these shape cues. This may reflect an efficient strategy of representing
      cues for image segmentation and object shape using finite neuronal resources.

PMID- 14570254
TI  - N-methyl-D-aspartate receptors contribute to the baseline noise of retinal
      ganglion cells.
AB  - Whole-cell recordings of tiger salamander ganglion cells were obtained using a
      superfused retinal slice preparation. Membrane current fluctuations were recorded
      under voltage-clamp conditions with cells usually held at -70 mV. Current
      fluctuations at rest (Mg2+ = 1 mM) were reduced by adding D-2-amino-7
      phosphonoheptanoate (D-AP7). Resting fluctuations were increased by adding N
      methyl-D-aspartate (NMDA) or by removing extracellular Mg2+. These increased
      fluctuations were blocked by D-AP7. Blocking NMDA receptors under control
      conditions also reduced a tonic inward current by -1 to -15 pA. Fluctuation
      analysis of current noise shows that the noise power spectrum measured in the
      presence of NMDA is similar to that measured under Mg(2+)-free conditions. We
      conclude that NMDA receptors are active in cells held at -70 mV even in the
      presence of 1 mM Mg2+. We believe this activation is due to the presence of
      endogenous glutamate in the retina. The observations of this study strongly
      suggest that NMDA receptors contribute to the resting noise and conductance
      properties of retinal ganglion cells. Our results suggest NMDA receptors are
      activated by an ambient level of extracellular glutamate whose source has yet to
      be determined.

PMID- 14570255
TI  - Functional relationship between nucleus isthmi and tectum in teleosts: synchrony
      but no topography.
AB  - Neural activity in the optic tectum was compared with activity in the nucleus
      isthmi (NI) of both goldfish and sunfish with the aim of understanding how the
      two brain structures interact to process visual information. The two species
      yielded very similar results. Superficial tectum responds reliably to visual
      stimulation with topographically organized receptive fields; deep tectum and NI
      respond to stimulation throughout the field of the contralateral eye and
      habituate rapidly. Bursts of large-amplitude spiking in NI occur spontaneously
      and in response to contralateral visual stimulation. These NI bursts correlate
      with activity bursts across the tectal lobe on the same side, especially in the
      deeper layers. NI bursts may also synchronize with spiking activity in deep
      tectum. Trains of small-amplitude spikes in NI can be elicited by both
      ipsilateral and contralateral stimulation, but are not reflected in tectal
      activity. Simultaneous recordings from two sites in one NI were almost identical,
      suggesting that NI operates as a functional unit, broadcasting the same message
      across the ipsilateral tectal lobe.

PMID- 14570256
TI  - Interview with Gerald Feldman, radiation safety officer.

PMID- 14570257
TI  - Neutron production associated with radiotherapy linear accelerators using
      intensity modulated radiation therapy mode.
AB  - A number of experiments were conducted on a Clinac 21EX radiotherapy accelerator
      using an IMRT treatment plan to determine neutron dose equivalent as a function
      of both patient dose delivered and machine workload. It was determined that IMRT
      mode is more neutron dose intensive as a function of patient dose when compared
      to a similar standard non-IMRT treatment. It was found that when the neutron
      production is normalized to workload, the measured neutron dose equivalents are
      similar. It is therefore recommended that neutron production be reported as a
      function of workload when considering IMRT treatment modes.

PMID- 14570258
TI  - Radiation safety compliance issues at affiliated institutions.
AB  - "Affiliation" may be defined as a collaborative interaction between two (or more)
      organizations in a spirit of mutual benefit through an equitable contribution of
      resources. Across the United States, hundreds of medical schools and healthcare
      organizations affiliate with one another for the enhancement of patient care,
      education, and research. Oftentimes, both parties in the affiliation have active
      clinical and research programs that involve the use of radioactive material
      (RAM). The combination of this close affiliation and use of radioactive material
      presents a number of challenging radiation safety compliance issues. It is
      important for radiation safety professionals (RSPs) employed by each affiliate to
      work together to ensure compliance with applicable regulatory requirements.

PMID- 14570259
TI  - False CAM alarms from radon fluctuations.
AB  - The root cause of many false continuous air monitor (CAM) alarms is revealed for
      CAMs that use constant spectral shape assumptions in transuranic (TRU) alpha
      activity determination algorithms. This paper shows that when atmospheric radon
      levels continually decrease and bottom out at a minimum level, reduced false TRU
      count rates are not only expected but measured. Similarly, when the radon levels
      continually increase to a maximum level, elevated false TRU count rates were
      measured as predicted. The basis for expecting this dependence on changes in
      radon levels is discussed.

PMID- 14570260
TI  - Security of radioactive material at academic institutions.
AB  - In recent years, regulatory emphasis on the prevention of loss, theft and
      intentional misuse of radioactive materials at academic institutions has forced
      radiation safety personnel to devote increasing amounts of time and effort to
      address security issues. NRC regulations require that radioactive materials used
      or stored in controlled or unrestricted areas be secure from unauthorized removal
      or be under constant surveillance when in use. This leaves open to interpretation
      what types of security are required for radioactive materials in restricted
      areas. Adhering to the goal of keeping exposures As Low As Reasonable Achievable
      (ALARA), a risk-based system for radioactive materials security in a university
      setting is proposed based on Annual Limits of Intake (ALI). This system
      establishes levels of security based on physical form, activity and
      concentration. Using this system, radiation safety personnel can more effectively
      establish reasonable security measures for radioactive material consistent with
      minimizing the realistic potential of serious harm or injury.

PMID- 14570261
TI  - A radiation protection program prospectus based on the collection of 10 years of
      key performance indicator data.
AB  - In 1992, the University of Texas Health Science Center at Houston Radiation
      Safety Program began assembling data on a monthly basis that described various
      program activities. At the end of calendar year 2002, a decade of data had been
      collected, so the information was summarized into a novel program prospectus,
      displaying various indicator parameters in a format similar to that used in a
      commercial enterprise prospectus provided to potential investors. The consistent
      formatting of the data afforded a succinct and easily digestible snapshot of
      program activities and trends. Feedback from various program stakeholders, even
      those unschooled in radiation safety matters, was overwhelmingly positive. The
      prospectus aided in communicating the scope of work undertaken by the program,
      and has helped maintain program support, even in challenging economic times. The
      data summary is also proving to be useful in making future projections regarding
      program needs.

PMID- 14570262
TI  - Programs and procedures for a large x-ray safety program.
AB  - As radiation safety surveys of x-ray equipment are the responsibility of many
      health physicists, actual procedures vary among facilities. In an effort to share
      survey methodology of a large research institution, aspects of the x-ray safety
      program at Los Alamos National Laboratory are described. A definition of an
      intentional x-ray generating device is proposed in light of the absence or
      inadequacy of such a definition in applicable federal law and national consensus
      guidance documents. Regulations and procedures are discussed, and a sample
      database used in managing the Los Alamos program is presented.

PMID- 14570263
TI  - Validation of the integrity of a HEPA filter system.
AB  - The objective of this study was to establish a delayed air sampling method to
      verify the integrity of an existing HEPA filter system in a ventilated fume hood.
      (238U,232Th)O2 microspheres were generated to fabricate cement nuclear fuel
      pellets in a HEPA-filtered hood. To comply with the air effluent concentration
      limits by NRC, the capture efficiency of the HEPA filter was examined. An in-line
      isokinetic air sampling system was installed downstream of the HEPA filter.
      Utilizing a gas flow proportional counter, 212Pb was used as a surrogate to
      indicate any possible penetration of the (238U,232Th)O2 particles through the
      HEPA filter. Based on the experimental results, this delayed sampling method
      proved to be an easy and effective way to validate the integrity of the HEPA
      filter.

PMID- 14570264
TI  - Chitinase-mediated inhibitory activity of Brassica transgenic on growth of
      Alternaria brassicae.
AB  - Chitinase, capable of degrading the cell walls of invading phytopathogenic fungi,
      plays an important role in plant defense response, particularly when this enzyme
      is overexpressed through genetic engineering. In the present study, Brassica
      plant (Brassica juncea L.) was transformed with chitinase gene tagged with an
      overexpressing promoter 35 S CaMV. The putative transgenics were assayed for
      their inhibitory activity against Alternaria brassicae, the inducer of Alternaria
      leaf spot of Brassica both in vitro and under polyhouse conditions. In in vitro
      fungal growth inhibition assays, chitinase inhibited the fungal colony size by 12
      56% over the non-trangenic control. The bioassay under artificial epiphytotic
      conditions revealed the delay in the onset of disease as well as reduced lesion
      number and size in 35S-chitinase Brassica as compared to the untransformed
      control plants.

PMID- 14570265
TI  - AHL-deficient mutants of Burkholderia ambifaria BC-F have decreased antifungal
      activity.
AB  - Burkholderia ambifaria BC-F, a biocontrol strain reported previously to exhibit
      broad-spectrum antifungal activity, was highly active in formation of N-acyl
      homoserine lactones (AHLs). We constructed AHL-deficient derivatives of strain BC
      F in which the genes specifying AHL synthase (bafI) and AHL-binding
      transcriptional activator (bafR) were inactivated by allelic exchange. The
      resulting AHL-deficient mutants had decreased antifungal activity.

PMID- 14570266
TI  - Construction of secretory expression system suitable to express glucagon under
      the control of PL promoter.
AB  - It was reported that PL promoter and alkaline phosphatase (phoA) signal peptide
      were used to construct secretory expression plasmid suitable to express glucagon
      and [Des-His1] glucagon in E. coli BL21 herein. Expression studies showed these
      two peptides could be expressed and secreted into the culture medium. The
      expression yield of recombinant glucagon reached 3.46 mg/L/OD600 unit of cells in
      shake flask. The yield of [Des-His1] glucagon was found to be higher than that of
      glucagon. In addition, some factors involved in secretion were studied too.

PMID- 14570267
TI  - Factors influencing the production of a novel compound, 7,10-dihydroxy-8(E)
      octadecenoic acid, by Pseudomonas aeruginosa PR3 (NRRL B-18602) in batch
      cultures.
AB  - Pseudomonas aeruginosa PR3 (NRRL B-18602) converts oleic acid to a novel
      compound, 7,10-dihydroxy-8(E)-octadecenoic acid (DOD). Parameters that included
      medium volume, cell growth time, gyration speed, pH, substrate concentration, and
      dissolved oxygen concentration were evaluated for a scale-up production of DOD in
      batch cultures using Fernbach flasks and a bench-top bioreactor. Maximum
      production of about 2 g DOD (38% yield) was attained in Fernbach flasks
      containing 500 ml medium when cells were grown at 28 degrees C and 300 rpm for 16
      20 h and the culture was adjusted to pH 7 prior to substrate addition. Increases
      of medium volume and substrate concentration failed to enhance yield. When batch
      cultures were initially conducted in a reactor, excessive foaming occurred that
      made the bioconversion process inoperable. This was overcome by a new aeration
      mechanism that provided adequate dissolved oxygen to the fermentation culture.
      Under the optimal conditions of 650 rpm, 28 degrees C, and 40-60% dissolved
      oxygen concentration, DOD production reached about 40 g (40% yield) in 4.5 L
      culture medium using a 7-L reactor vessel. This is the first report on a
      successful scale-up production of DOD.

PMID- 14570268
TI  - Overexpression of peroxisomal malate dehydrogenase MDH3 gene enhances cell death
      on H2O2 stress in the ald5 mutant of Saccharomyces cerevisiae.
AB  - Mitochondrial aldehyde dehydrogenase ALD5 of Saccharomyces cerevisiae is involved
      in the biosynthesis of mitochondrial electron transport chain, and the ald5
      mutant is incompetent for respiration. With use of the mutant, we examined the
      detoxication of H2O2 generation by fatty acid beta-oxidation in peroxisome. The
      ald5 mutant (AKD321), as well as the 746 rho0 mutant, was more resistant to H2O2
      stress than the wild type. However, overexpression of the MDH3 gene that was
      involved in the reoxidation of NADH during fatty acid beta-oxidation caused a
      decrease in cell viability of AKD321 to H2O2 stress, while the 746 rho0 mutant
      had no such effect. Intracellular H2O2 concentration increased approximately
      fourfold in MDH3 overexpressing ald5 strain (MD3-AKD321), compared with AKD321.
      The peroxisomal catalase activity of MD3-AKD321 decreased by 83% to that of
      AKD321. And also, the overexpression of MDH3 had only a weak effect in MDH3
      overexpressing 746 rho0 strain, decreasing by 14% to that of 746 rho0 mutant. The
      increased palmitoyl CoA oxidation by overexpression of MDH3 gene was the same in
      both strains. Under conditions of MDH3 overexpression, peroxisomal catalase
      (CTA1) appears to be a limiting factor to oxidative stress. These observations
      point to an important, as yet unidentified, role of mitochondrial aldehyde
      dehydrogenase (ALD5) to endogeneous oxidative stress in peroxisome.

PMID- 14570269
TI  - A novel and simple method for the purification of extracellular levansucrase from
      Zymomonas mobilis.
AB  - A new and simple method for the purification of extracellular levansucrase from
      Zymomonas mobilis from highly viscous fermentation broth was developed. After
      incubation of the fermentation broth with a fructose-polymer cleaving enzyme
      preparation (Fructozyme, Novozymes, DK) for 48 h, levansucrase precipitated as
      aggregates and was redissolved in a 3 M urea solution. By ongoing size-exclusion
      chromatography on Sephacryl S-300 the final levansucrase preparation was purified
      100-fold and exhibited a specific activity of 25-35 U/mg(protein). The
      levansucrase was stable in 3 M urea solution for at least four months without
      inactivation. To maximize the enzyme yield the dynamic changes of extracellular
      levansucrase activity during fermentation were investigated. The highest
      levansucrase activity was observed during the logarithmic phase of growth (15-19
      h of fermentation).

PMID- 14570270
TI  - Characterization and transcription of the genes encoding enzymes involved in
      butyrate production in Butyrivibrio fibrisolvens.
AB  - Genes encoding enzymes that catalyze butyryl-CoA formation from acetyl-CoA in a
      type II strain of Butyrivibrio fibrisolvens were analyzed. The genes encoding
      thiolase, beta-hydroxybutyryl-CoA dehydrogenase, butyryl-CoA dehydrogenase, and
      electron transfer flavoproteins were clustered, but the crotonase gene was not
      present in this region. The deduced amino acid sequences of these enzymes were
      similar to those of clostridia. The clustered genes were shown to be
      cotranscribed. The rate of butyrate production increased with an increase in
      acetate concentration in the medium up to 5 mM, suggesting that the butyryl
      CoA/acetate CoA transferase reaction limits butyrate production. Transcription of
      the clustered genes was not affected by acetate concentration, suggesting that
      acetate does not affect the synthesis of enzymes involved in butyryl-CoA
      formation. These results confirm that acetate stimulates butyrate production by
      acting as a CoA acceptor in the butyryl-CoA/acetate CoA transferase reaction.

PMID- 14570271
TI  - Effect of glutamate synthase (GOGAT) activity on Bacillus subtilis spore
      properties.
AB  - The role of glutamate as osmoprotector was investigated through the study of a
      mutation in its biosynthetic pathway. A glt::Tn917-lacZ-cat insertion mutant (N1)
      conferring glutamate auxotrophy and enhanced beta-galactosidase expression on
      high-salt media was selected. Co-transformation experiments and PCR analysis
      allowed locating the insertion into the gltB gene corresponding to the small unit
      of the glutamate synthase (GOGAT). The N1 mutant strain presented a glutamate
      requirement for growth and a tenfold decrease in GOGAT activity. Transcriptional
      activity of GOGAT, measured as beta-galactosidase from the transposon fusion,
      correlated with enzymatic activity; expression was enhanced at the stationary
      phase and in high-ionic-strength media. However, osmotolerance of cultures of N1
      mutant were as wild-type (wt), at least in semi-rich medium. In contrast,
      sporulation was slightly reduced (75% of wt), and spores were less resistant to
      UV, heat, and osmolarity, properties linked to the content of small, acid-soluble
      proteins (SASP). The content of these proteins was, in fact, reduced, in
      particular the SASP-gamma type. The peptidoglycan-cortex, however, was not
      impaired since spores maintained lysozyme resistance. Addition of glutamate
      during sporulation partially rescued spore resistance, but germination and
      outgrowth remained impaired. Deficiencies in germination and outgrowth were also
      observed with spores from a gltA mutant strain. Taken together, these results
      pointed to the importance of GOGAT activity during sporulation, in particular for
      the synthesis SASPs.

PMID- 14570272
TI  - Genus- and isolate-specific real-time PCR quantification of Erwinia on leaf
      surfaces of English oaks (Quercus robur L.).
AB  - In order to quantify pathogenic epiphytic bacteria on leaf surfaces of the
      important European forest tree Quercus robur without time-intensive cultivation
      and separation of microorganisms, methods were developed to selectively quantify
      DNA copy numbers of the genus Erwinia in DNA isolated from the leaf surface. By
      using the combination of the two different real-time PCR techniques SYBR-Green
      and TaqMan, methods were developed not only to allow quantification of the total
      DNA copy number of Erwinia on the oak leaf surface, but also to distinguish
      between two significantly different groups of Erwinia strains. In the present
      work, these techniques were successfully applied to quantify the copy number of
      the genus Erwinia and its subgroups compared with the total bacteria number in
      DNA samples extracted from the upper leaf surface of English oaks collected on
      the 4th of June 2001 (Julian day 155).

PMID- 14570273
TI  - Silencing of hygromycin phosphotransferase (hph) gene during sexual cycle and its
      reversible inactivation in heterokaryon of Neurospora crassa.
AB  - We transformed wild-type Neurospora crassa with hph gene encoding hygromycin
      phosphotransferase to obtain hygromycin-resistant (HygR) transformants and
      studied their behavior in the vegetative and sexual phases of growth. During
      vegetative growth in the absence of hygromycin, the hph gene was stable for at
      least three successive transfers with conidia. On the other hand, the behavior of
      the transformants in the sexual phase was different. The segregation of hph gene
      in the meiotic progeny was in accordance with the Mendelian ratio as inferred
      from PCR analysis. However, in spite of inheriting the hph gene, a proportion of
      the meiotic progeny failed to grow in the presence of hygromycin. This suggested
      that the hph gene is silenced in some progeny. The silencing effect was not
      confined to hph gene expression, since one-half of the meiotic progeny also
      showed poor conidiation. Genomic Southern analysis indicated
      deletions/rearrangements of the transgene in the progeny. A heterokaryon between
      silenced and non-silenced strains was able to grow on hygromycin-containing
      medium, showing that silencing was recessive. Silencing was reversed in
      homokaryotic nuclei extracted from such heterokaryon.

PMID- 14570274
TI  - Toxicity of Bacillus sphaericus LP1-G against susceptible and resistant Culex
      quinquefasciatus and the cloning of the mosquitocidal toxin gene.
AB  - Bacillus sphaericus LP1-G, belonging to flagellar serotype H3, has been found to
      have moderate toxicity against two resistant Culex quinquefasciatus colonies
      (RLCq1 and RLCq2) and the susceptible contrast (SLCq). With an aim of screening
      mosquitocidal acting factor, a partial genome library was prepared from a partial
      HindIII digest of the total DNA from Bacillus sphaericus LP1-G. Two thousand
      twenty Escherichia coli clones were screened for toxicity against susceptible
      SLCq, and a toxic clone, designated E-UL68, was chosen for further study. The
      recombinant E-UL68 performed toxicity against both susceptible and two resistant
      colonies, having the same level of toxicity as that of wide-type strain LP1-G.
      Sequence analysis revealed that the inserted fragment was composed of 3876
      nucleotides and contained a complete gene, whose sequence was identical to that
      of the mtx gene from B. sphaericus SSII-1. Because the binary toxin produced
      during sporulation of strain LP1-G has no activity against the target mosquitoes,
      this indicates that the Mtx toxin or other active factors might perhaps be
      responsible for the toxicity of LP1-G against different colonies of mosquito
      larvae.

PMID- 14570275
TI  - The screening of hydrogen peroxide-producing lactic acid bacteria and their
      application to inactivating psychrotrophic food-borne pathogens.
AB  - Lactic acid bacteria were isolated from various food samples and evaluated for
      hydrogen peroxide (H2O2) production. Cells suspended in 0.5% (wt/vol) glucose
      plus 0.5% (wt/vol) lactate (pH 7.0) were incubated for 5 h at 37 degrees C under
      aeration. Among 193 strains, 27 strains accumulated 201-300 ppm H2O2, and 4
      strains accumulated more than 301 ppm H2O2 in the cell suspensions. Among the 9
      high-level H2O2-producing strains, 8 strains were identified as Lactococcus
      lactis subsp. lactis. The cell-free filtrate from Lc. lactis subsp. lactis AI 62,
      which contained approximately 350 ppm H2O2, was evaluated for antimicrobial
      activity against Enterococcus faecalis, Ent. faecium, enterotoxigenic Escherichia
      coli, Listeria ivanovii, Staphylococcus aureus, Yersinia enterocolitica, and
      Aeromonas hydrophila. After 1 h incubation at 30 degrees C in the cell-free
      filtrate, the initial viable cell counts of the target bacteria (5.53-6.00 log
      cfu/mL) were reduced by 0.12-5.00 log units, except in the case of enterococci.
      The sensitivity varied with the bacterial species and pH. The enterococci were
      resistant to the treatment. Our results show that H2O2 accumulated by lactic acid
      bacteria in a cell suspension is very effective in reducing the viable cell count
      of food-borne pathogens.

PMID- 14570276
TI  - Neomycin and paromomycin inhibit 30S ribosomal subunit assembly in Staphylococcus
      aureus.
AB  - A number of different antibiotics that prevent translation by binding to the 50S
      ribosomal subunit of bacterial cells have recently been shown to also prevent
      assembly of this subunit. Antibacterial agents affecting 30S particle activities
      have not been examined extensively for effects on small subunit formation. The
      aminoglycoside antibiotics paromomycin and neomycin bind specifically to the 30S
      ribosomal subunit and inhibit translation. These drugs were examined in
      Staphylococcus aureus cells to see whether they had a second inhibitory effect on
      30S particle assembly. A 3H-uridine pulse and chase assay was used to examine the
      kinetics of subunit synthesis in the presence and absence of each antibiotic. 30S
      subunit formation was inhibited by both compounds. At 3 microg/mL each antibiotic
      reduced the rate of 30S formation by 80% compared with control cells. Both
      antibiotics showed a concentration-dependent inhibition of particle formation,
      with a lesser effect on 50S particle formation. For neomycin, the IC50 for 30S
      particle formation was equal to the IC50 for inhibition of translation. Both
      antibiotics reduced the viable cell number with an IC50 of 2 microg/mL. They also
      inhibited protein synthesis in the cells with different IC50 values (2.5 and 1.25
      microg/mL). This is the second demonstration of 30S ribosomal subunit-specific
      antibiotics that prevent assembly of the small subunit.

PMID- 14570277
TI  - A combination effect of epigallocatechin gallate, a major compound of green tea
      catechins, with antibiotics on Helicobacter pylori growth in vitro.
AB  - Since green tea catechins are known to have antimicrobial activity against a
      variety of microorganisms, their possible effects on Helicobacter pylori in
      combination with antibiotics were examined. Fifty-six clinical isolates of H.
      pylori, including 19 isolates highly resistant to metronidazole (MTZ) and/or
      clarithromycin (CLR), were used to determine in vitro sensitivity to tea
      catechins. The MIC90 of both epigallocatechin gallate (EGCg) and epicatechin
      gallate (ECg) was 100 microg/ml. However, other tea catechins tested did not show
      any anti-H. pylori activity. Highly antibiotic-resistant clinical isolates showed
      a similar sensitivity to both EGCg and ECg. The kinetic study of antibacterial
      activity in liquid cultures revealed a relatively slow but strong activity on the
      growth of H. pylori. In combination with sub-MIC of amoxicillin (AMX), the
      antibacterial activity of AMX was significantly enhanced by the presence of EGCg.
      To estimate the general combination effect between EGCg and other antibiotics,
      such as MTZ and CLR, on the antibacterial activity against clinical isolates, the
      fraction inhibitory concentration (FIC) was determined by checkerboard study. The
      FIC indexes showed additive effects between EGCg and antibiotics tested. These
      results indicatethat EGCg may be a valuable therapeutic agent against H. pylori
      infection.

PMID- 14570278
TI  - Trapping of 2,7-dichlorodibenzo-p-dioxin in aqueous solution by enzymatic
      reaction of fungal manganese peroxidase in the presence of polyunsaturated fatty
      acids.
AB  - In the presence of polyunsaturated fatty acids, including cis-4,7,10,13,16,19
      docosahexaenoic acid (DHA), 2,7-dichlorodibenzo-p-dioxin (DCDD) was treated with
      manganese peroxidase (MnP) from white rot basidiomycete Phanerochaete sordida YK
      624. After incubation with MnP, DCDD could not be extracted from the reaction
      mixture with n-hexane and was trapped in the water layer. DCDD was released by
      alkalification of the water layer. DCDD was also trapped after treatment with
      lipoxidase, which produces hydroperoxides from unsaturated lipids. The amounts of
      thiobarbituric acid-reactive substances produced in the MnP reactions with three
      highly unsaturated fatty acids were higher than the amounts produced with three
      fatty acids with a lower degree of unsaturation. These results suggest that a
      DCDD-trapping compound may be produced by peroxidation of the polyunsaturated
      fatty acids.

PMID- 14570279
TI  - Nitrate uptake by the halotolerant cyanobacterium Aphanothece halophytica grown
      under non-stress and salt-stress conditions.
AB  - We have compared the characteristics of nitrate uptake by Aphanothece halophytica
      grown under non-stress and salt-stress conditions. Both cell types showed
      essentially similar patterns of nitrate uptake toward ammonium, nitrite, and DL
      glyceraldehyde. Although the affinities of nitrate to non-stress cells and salt
      stress cells were not significantly different, i.e., Ks = 416 and 450 microM,
      respectively, the V(max) value for non-stress cells was about twofold of that for
      salt-stress cells (9.1 vs 5.3 micromol min(-1) mg(-1) Chl). Nitrate uptake by A.
      halophytica was found to be dependent on Na+. Ammonium inhibited nitrate uptake,
      and the presence of methionine sulfoximine could not release the inhibition by
      ammonium. Nitrite appeared to competitively inhibit nitrate uptake with a K(i)
      value of 84 microM. Both chloride and phosphate anions did not affect nitrate
      uptake. DL-Glyceraldehyde, an inhibitor of CO2 fixation, caused a reduction in
      the uptake of nitrate.

PMID- 14570280
TI  - Cadmium-induced adaptive resistance and cross-resistance to zinc in Xanthomonas
      campestris.
AB  - Cadmium (Cd) and zinc (Zn) are environmental pollutants affecting both soil and
      water. The toxicity resulting from the exposure of Xanthomonas campestris, a soil
      bacterium and plant pathogen, to these metals was investigated. Pretreatment of
      X. campestris with sub-lethal concentrations of Cd induced adaptive protection
      against subsequent exposure to lethal doses of Cd. Moreover, Cd-induced cells
      also showed cross-resistance to lethal concentrations of Zn. These induced
      protections required newly synthesized proteins. Unexpectedly, Zn-induced cells
      did not exhibit adaptive protection against lethal concentrations of Zn or Cd.
      These data suggested that the increased resistance to Cd and Zn killing probably
      involved other protective mechanisms in addition to ion efflux.

PMID- 14570281
TI  - Pathological changes in the cerebral medullary arteries of five autopsy cases of
      malignant nephrosclerosis: observation by morphometry and reconstruction of
      serial sections.
AB  - Hypertension (HT) is a serious risk factor of not only cerebral infarction and
      bleeding, but also Binswanger's encephalopathy (BE). In BE especially, severe
      stiffening of the cerebral medullary arteries because of hypertensive changes
      with loss of medial smooth muscle cells (SMC) occurs, which induces diffuse
      atrophy of the cerebral white matter. But, it is not yet ascertained whether HT
      is particularly severe in BE. Therefore, a spectrum of the pathological changes
      of the cerebral arteries were investigated by reconstruction of serial sections
      and morphometry of the medial thickness in five autopsied patients with malignant
      nephrosclerosis (MN) of exacerbated form. Each presented clinically acute
      progression of long-standing HT at the terminal stage and pathologically typical
      renal changes. The heartweight was 380-900 g. Morphometry of the medial thickness
      of the arachnoid arteries presented significant medial hypertrophy in four cases
      of MN, but in the medullary arteries it presented in only two cases with marked
      cardiomegaly of 700 g and 900 g. In four cases of MN, only a few medullary
      arteries showed slight pathological changes. However, in another case with
      cardiomegaly of 900 g, all 10 medullary arteries showed multiple segments of
      atheroma, medial SMC loss, and prominent dilatation; edematous concentric intimal
      fibrosis with luminal obstruction and atrophy of the white matter were absent. In
      conclusion, only one case of MN showing marked cardiomegaly of 900 g presented
      severe pathological changes of the cerebral medullary arteries comparable with
      those of BE, although other MN-cases showing severe cardiac hypertrophy presented
      only trivial arterial changes. Therefore, the cerebral medullary artery seems to
      be protected from HT, yet it is involved in a case of severe and long-standing HT
      inducing an extreme cardiomegaly.

PMID- 14570282
TI  - 6-Formylpterin protects retinal neurons from transient ischemia-reperfusion
      injury in rats: a morphological and immunohistochemical study.
AB  - Neuroprotective effects of 6-formylpterin (6FP) on transient retinal ischemia
      reperfusion injury were evaluated in rats by means of counting the number of
      retinal ganglion cells, measuring the thicknesses of the inner plexiform and
      inner nuclear layers, and by immunohistochemical detection of apoptotic cells in
      the retina. Sixty-one Sprague-Dawley rats (12 weeks, male, 295-330 g) were
      subjected to transient retinal ischemia-reperfusion by elevated intra-ocular
      pressure (80 mmHg for 60 min). Intraperitoneal injection of 6FP (3.8 mg/kg) was
      performed before or after ischemia. The retina was histologically better
      preserved in rats with 6FP treatment than without 6FP treatment. 6FP showed more
      strong neuroprotective effects when it was administered before ischemia. The
      number of single-stranded DNA-positive cells in the retina also decreased
      remarkably in rats with 6FP treatment, especially when administered before
      ischemia. These results suggest that 6FP protects retinal neurons from transient
      ischemia-reperfusion injury, at least in part by inhibiting apoptotic cell death.

PMID- 14570283
TI  - Migration and differentiation of nuclear fluorescence-labeled bone marrow stromal
      cells after transplantation into cerebral infarct and spinal cord injury in mice.
AB  - There is increasing evidence that bone marrow stromal cells (BMSC) have the
      potential to migrate into the injured neural tissue and to differentiate into the
      CNS cells, indicating the possibility of autograft transplantation therapy. The
      present study was aimed to clarify whether the mouse BMSC can migrate into the
      lesion and differentiate into the CNS cells when transplanted into the mice
      subjected to focal cerebral infarct or spinal cord injury. The BMSC were
      harvested from mice and characterized by flow cytometry. Then, the BMSC were
      labeled by bis-benzimide, a nuclear fluorescence dye, over 24 h, and were
      stereotactically transplanted into the brain or spinal cord of the mice. The
      cultured BMSC expressed low levels of CD45 and high levels of CD90 and Sca-1 on
      flow cytometry. A large number of grafted cells survived in the normal brain 4
      weeks after transplantation, many of which were located close to the transplanted
      sites. They expressed the neuronal marker including NeuN, MAP2, and doublecortin
      on fluorescent immunohistochemistry. However, when the BMSC were transplanted
      into the ipsilateral striatum of the mice subjected to middle cerebral artery
      occlusion, many of the grafted cells migrated into the corpus callosum and
      injured cortex, and also expressed the neuronal markers 4 weeks after
      transplantation. In particular, NeuN was very useful to validate the
      differentiation of the grafted cells, because the marker was expressed in the
      nuclei and was overlapped with bis-benzimide. Similar results were obtained in
      the mice subjected to spinal cord injury. However, many of the transplanted BMSC
      expressed GFAP, an astrocytic protein, in injured spinal cord. The present
      results indicate that the mouse BMSC can migrate into the CNS lesion and
      differentiate into the neurons or astrocytes, and that bis-benzimide is a simple
      and useful marker to label the donor cells and to evaluate their migration and
      differentiation in the host neural tissues over a long period.

PMID- 14570284
TI  - A quantitative study of the pathological changes in cortical neurons in sporadic
      Creutzfeldt-Jakob disease.
AB  - The frequency of morphological abnormalities in neuronal perikarya was studied in
      the cerebral cortex in cases of sporadic CJD (sCJD) and in elderly control
      patients. Three hypotheses were tested, namely that the proportion of neurons
      exhibiting abnormal morphology was increased: (i) in sCJD compared with control
      patients; (ii) in sCJD, in areas with significant prion protein (PrP) deposition
      compared with regions with little or no PrP deposition; and (iii) when neurons
      were spatially associated with a PrP deposit compared with neurons between PrP
      deposits. Changes in cell shape (swollen or atrophic cell bodies), nuclei
      (displaced, indistinct, shrunken or absent nuclei; absence of nucleolus), and
      cytoplasm (dense or pale cytoplasm, PrP positive cytoplasm, vacuolation) were
      commonly observed in all of the cortical areas studied in the sCJD cases. The
      proportion of neurons exhibiting each type of morphological change was
      significantly increased in sCJD compared with age-matched control cases. In sCJD,
      neuronal abnormalities were present in areas with little PrP deposition, but at
      significantly lower frequencies compared with areas with significant densities of
      PrP deposits. Abnormalities of cell shape, nucleus and the presence of
      cytoplasmic vacuolation were increased when the neurons were associated with a
      PrP deposit, but fewer of these neurons were PrP-positive compared with neurons
      between deposits. The data suggest significant neuronal degeneration in the
      cerebral cortex in sCJD in areas without significant PrP deposition and a further
      phase of neuronal degeneration associated with the appearance of PrP deposits.

PMID- 14570285
TI  - Influence of experimental chronic hypertension on the cerebral and renal arteries
      of wild cats.
AB  - The influence of chronic hypertension (HT) on the cerebral and renal arteries was
      examined pathologically and morphometrically in wild cats without a specific
      genetic background. Chronic HT for 8-15 months was induced by uninephrectomy and
      salt-loading, and the blood pressure was monitored for a maximum of 5 months. The
      grade of systolic blood pressure elevation in each cat during the monitoring
      period was 21-51 mmHg. Histologically, the cerebral arachnoid and medullary
      arteries of all hypertensive cats showed a well-preserved medial layer, and
      neither loss of medial smooth muscle cells, adventitial fibrosis or fibrinoid
      exudation was detected. This experimental model of chronic HT in wild cats for 8
      15 months induced segmental intimal elastofibrosis of the arachnoid and renal
      arteries, but spared the cerebral medullary artery. The parenchymal changes in
      the brain were negligible. Morphometrically, the arachnoid artery in control cats
      had a significantly thinner media than the renal artery, and the medial
      hypertrophy of the arachnoid artery resulting from HT occurred significantly less
      frequently than that of the renal artery. These findings suggest that the
      arachnoid and medullary arteries are relatively well protected from HT, and that
      this may be characteristic of cerebral arteries in general and ascribed to
      autoregulation.

PMID- 14570286
TI  - Non-traumatic recurrent dissection and its spontaneous repair in the circle of
      Willis: report of two autopsy cases.
AB  - Post-mortem examinations of the circle of Willis in two cases of subarachnoid
      hemorrhage disclosed a wide spectrum of vasculopathy ranging from a minimal tear
      between the intima and media, and between the media and adventitia, to complete
      transmural disruption leading to the formation of pseudoaneurysms. The presence
      of coexistence of the focal lesions with complete replacement of the entire
      arterial wall with thick fibrous connective tissues and the vasculopathy was
      suggestive of the spontaneous repair of recurrent non-traumatic dissection of
      intracranial arteries. The patients were 58-year-old and 43-year-old females.
      There was no history of injury to the head or neck in either case. They were
      hypertensive, but the degree of atherosclerotic changes in the circle of Willis
      was compatible with age. There was no histological evidence of vasculitis. The
      role of hypertension and medial mucoid degeneration in the genesis of non
      traumatic dissection of intracranial arteries was discussed.

PMID- 14570287
TI  - Glycogen synthase kinase-3beta phosphorylates synphilin-1 in vitro.
AB  - alpha-Synuclein is known to be a major component of Lewy bodies and glial
      cytoplasmic inclusions in the brains of patients with alpha-synucleinopathies.
      Synphilin-1, an alpha-synuclein-associated protein, is also present in these
      inclusions. However, little is known about the post-translational modifications
      of synphilin-1. In the present study, it is reported that synphilin-1 is
      phosphorylated by glycogen synthase kinase-3beta in vitro. It is well known that
      protein phosphorylation is involved in various physiological phenomena, including
      signal transduction and protein degradation. Therefore, phosphorylation of
      synphilin-1 may play an important role in the function of this protein in the
      brain.

PMID- 14570288
TI  - A comparative immunohistochemistry of O6-methylguanine-DNA methyltransferase and
      p53 in diffusely infiltrating astrocytomas.
AB  - The DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) removes
      mutagenic adducts from the O6 position of guanine, thereby protecting the genome
      against guanine : cytosine to adenine : thymine transition and, meanwhile,
      conferring tumor resistance to many anti-cancer alkylating agents commonly used
      in the treatment of malignant gliomas. Studies on the involvement of p53 protein
      in expression of the MGMT gene have provided conflicting results regarding the
      relation between p53 protein and MGMT gene expression. To examine the potential
      immunostaining pattern of MGMT expression and to evaluate the possible
      relationship between p53 and MGMT regulation, we assessed MGMT and p53
      accumulation on 35 cases of diffusely infiltrating astrocytomas. With a few cases
      showing cytoplasmic staining, MGMT accumulation was mainly nuclear. The
      percentage of labeled tumor cells was lower in high-grade astrocytomas than in
      low-grade astrocytomas (P < 0.05). Additionally, p53-immunopositive tumor cells
      were usually immunonegative to MGMT. Thus, it is suggested that MGMT expression
      is reduced during malignant transformation of diffusely infiltrating
      astrocytomas, and that mutant p53 protein might be associated with down
      regulation of the MGMT expression.

PMID- 14570289
TI  - Ultrasound agents may open the blood-brain barrier in rats and aggravate
      pathologic consequences of experimental head trauma.
AB  - Unilateral intracarotid injection of contrast agents may considerably destabilize
      the blood-brain barrier in rats. This leads to vasogenic edema in the ipsilateral
      hemisphere. Mortality and extravasation increased significantly when
      administration of these ultrasound contrast agents was followed by mild traumatic
      brain injury. Direct administration to the cerebral circulation is, therefore,
      indicative for edema-related pathology and may amplify the consequences of
      experimental neurotrauma.

PMID- 14570290
TI  - Pilocytic astrocytoma of neurohypophysis.
AB  - A case of pilocytic astrocytoma of neurohypophysis is presented. The clinical,
      pathological and MRI features of a rare tumor of the neurohypophysis are
      described. A 5-year-old girl presented with a 3 month history of lethargy,
      imbalance and visual disturbances. A MRI revealed a large suprasellar mass.
      Histopathological examination demonstrated a pilocytic astrocytoma. Its
      astrocytic nature was confirmed by positive immunostaining for GFAP and the
      findings of an electron microscopy.

PMID- 14570291
TI  - Intraepithelial carcinoma arising in an endodermal cyst of the posterior fossa.
AB  - Endodermal cysts of the central neuraxis are benign, non-neoplastic epithelium
      lined cysts arising from endodermal tissue that have been displaced early in
      fetal life. Intracranial endodermal cysts are rare and usually located in the
      posterior fossa. The present study involves a 36-year-old man with a typical
      epithelial cyst in the posterior fossa. Microscopically, the cyst has a simple
      columnar epithelium with mucus-producing cells, containing an area composed of
      dysplastic epithelium with evidence of an intraepithelial carcinoma. The atypical
      cells have a high proliferative fraction demonstrated by Ki-67 immunostain. Based
      on these findings, the authors view this case as evidence of a malignant
      transformation of a classic endodermal cyst. The clinicopathologic features and a
      review of the literature are discussed.

PMID- 14570292
TI  - Primary squamous cell carcinoma of the brain. A rare autopsy case.
AB  - In the present study, a rare autopsy case of primary squamous cell carcinoma of
      the brain is described. The patient was a 49-year-old man who showed brainstem
      symptoms and signs. These included oculomotor, abducens and facial palsies,
      dysphagia, dysarthria, and long tract signs such as quadriplegia with Babinski's
      signs during the 3-year and 6-month course of his illness. Neuropathologically,
      poorly differentiated squamous cell carcinoma was seen in the pons, medulla
      oblongata, part of the midbrain and spinal cord, the base of the cerebellum, the
      hypothalamus, the optic chiasm, and the left parahippocampal gyrus. The base of
      the pons and medulla oblongata were extensively destroyed by tumor cells. The
      relevant literature regarding primary squamous cell carcinomas of the brain was
      reviewed, and the characteristic features of this rare condition were discussed.

PMID- 14570293
TI  - Anti-Hu paraneoplastic syndrome presenting with brainstem-cerebellar symptoms and
      Lambert-Eaton myasthenic syndrome.
AB  - Paraneoplastic syndrome (PNS) with two distinct neurological features was
      reported in a 50-year-old man who presented initially with vertigo, ataxia,
      dysarthria, tremor, confusion, urinary retention and hypotension. Pulmonary X-ray
      findings, class IIIb sputum cytology, and positive anti-Hu antibody established
      the diagnosis of PNS associated with small-cell lung cancer (SCLC). Two cycles of
      combined chemotherapy resulted in shrinkage of the lung tumor together with
      complete recovery of neurological symptoms and disappearance of anti-Hu antibody.
      Relapse of SCLC 4 months later with re-appearance of anti-Hu antibody required
      additional chemotherapy and irradiation. Eight months later, when multiple liver
      metastasis of SCLC was noticed, muscular weakness with positive waxing phenomenon
      compatible with Lambert-Eaton myasthenic syndrome (LEMS) developed. Postmortem
      examinations revealed residual SCLC in the primary lung, and massive liver
      metastasis with generalized lymph node involvement, but no tumors in the CNS. In
      the cerebellum, there was a slight loss of Purkinje cells with torpedo formation
      but without apparent lymphocytic infiltration. The present PNS was unique in that
      the relapse of SCLC was accompanied by the appearance of anti-Hu antibody, and
      that initial signs of brainstem-cerebellar symptoms, encephalopathy and autonomic
      failure were replaced by LEMS coinciding with the tumor recurrence.

PMID- 14570294
TI  - Use of regression modeling to simulate patient-specific decision analysis for
      patients with nonvalvular atrial fibrillation.
AB  - PURPOSE: To create a Web-based decision support tool that uses a simple
      regression equation to simulate performance of patient-specific decision analysis
      (PSDA) for patients with nonvalvular atrial fibrillation. METHODS: Patient-level
      data were used, along with decision model estimates of the gain in quality
      adjusted life expectancy associated with anticoagulant therapy to train
      regression models. Models involving successively higher order polynomial
      functions were evaluated. RESULTS: Quadratic (R2 = 0.89) and cubic (R2 = 0.97)
      regression models provided incremental benefit over a simple linear model (R2 =
      0.56). For the cubic model, 95% of estimates were within 0.26 QALYs of decision
      model estimates. The cubic model accurately predicted actual decision model
      recommendations (AUROC of 0.957). CONCLUSIONS: Regression modeling can be used to
      simulate the performance of PSDA for patients with atrial fibrillation. This
      approach can be used to create fast, reliable, and portable decision support
      tools to improve patient care.

PMID- 14570295
TI  - Public response to cost-quality tradeoffs in clinical decisions.
AB  - PURPOSE: To explore public attitudes toward the incorporation of cost
      effectiveness analysis into clinical decisions. METHODS: The authors presented
      781 jurors with a survey describing 1 of 6 clinical encounters in which a
      physician has to choose between cancer screening tests. They provided cost
      effectiveness data for all tests, and in each scenario, the most effective test
      was more expensive. They instructed respondents to imagine that he or she was the
      physician in the scenario and asked them to choose which test to recommend and
      then explain their choice in an open-ended manner. The authors then qualitatively
      analyzed the responses by identifying themes and developed a coding scheme. Two
      authors separately coded the statements with high overall agreement (kappa =
      0.76). Categories were not mutually exclusive. RESULTS: Overall, 410 respondents
      (55%) chose the most expensive option, and 332 respondents (45%) choose a less
      expensive option. Explanatory comments were given by 82% respondents. Respondents
      who chose the most expensive test focused on the increased benefit (without
      directly acknowledging the additional cost) (39%), a general belief that life is
      more important than money (22%), the significance of cancer risk for the patient
      in the scenario (20%), the belief that the benefit of the test was worth the
      additional cost (8%), and personal anecdotes/preferences (6%). Of the respondents
      who chose the less expensive test, 40% indicated that they did not believe that
      the patient in the scenario was at significant risk for cancer, 13% indicated
      that they thought the less expensive test was adequate or not meaningfully
      different from the more expensive test, 12% thought the cost of the test was not
      worth the additional benefit, 9% indicated that the test was too expensive
      (without mention of additional benefit), and 7% responded that resources were
      limited. CONCLUSIONS: Public response to cost-quality tradeoffs is mixed.
      Although some respondents justified their decision based on the cost
      effectiveness information provided, many focused instead on specific features of
      the scenario or on general beliefs about whether cost should be incorporated into
      clinical decisions.

PMID- 14570296
TI  - The impact of ignoring population heterogeneity when Markov models are used in
      cost-effectiveness analysis.
AB  - Many factors related to the spread and progression of diseases vary throughout a
      population. This heterogeneity is frequently ignored in cost-effectiveness
      analyses by using average or representative values or by considering multiple
      risk groups. The author explores the impact that such simplifying assumptions may
      have on the results and interpretation of cost-effectiveness analyses when Markov
      models are used to calculate the costs and health impact of interventions. A
      discrete-time Markov model for a disease is defined, and 5 potential
      interventions are considered. Health benefits, costs, and incremental cost
      effectiveness ratios are calculated for each intervention. It is assumed that the
      population is heterogeneous with respect to the probability of becoming sick.
      Ignoring this heterogeneity may lead to optimistic or pessimistic estimates of
      cost-effectiveness ratios, depending on the intervention and, in some cases, the
      parameter values. Implications are discussed of this finding on the use of league
      tables and on comparisons of cost-effectiveness ratios versus commonly accepted
      threshold values.

PMID- 14570297
TI  - Risk adjustment for people with chronic conditions in private sector health
      plans.
AB  - BACKGROUND: Although the problem of adverse selection into more generous health
      insurance plans has been the focus of previous work, risk adjustment systems have
      only recently begun to be implemented to blunt its effect. OBJECTIVES: This study
      examines the ability of the leading risk adjustment systems to predict health
      care expenditures for people with chronic conditions, using claims and enrollment
      data from 2 large employers. RESEARCH DESIGN: Predictive errors and total
      financial losses/gains are compared for different risk adjustment approaches
      (primarily hierarchical condition categories [HCCs] and adjusted clinical groups)
      for several chronic conditions. RESULTS: One of the best performing risk
      adjustment systems was a regression-based HCC method, which had an average under
      prediction error rate of 9% or 6%, depending on the employer. In comparison, more
      typical actuarial risk adjustments based on just age, gender, and prevailing area
      wages lead to a prediction error of at least 50%. We did not find evidence that
      payments for particular chronic conditions would be consistently and
      significantly under- or overestimated. CONCLUSION: The leading risk adjustment
      approaches substantially reduce the incentives for adverse selection but do not
      eliminate them.

PMID- 14570298
TI  - A priori risk and optimal test accuracy in prenatal diagnostics.
AB  - The prevalence of fetal chromosome anomalies rises exponentially with the age of
      the pregnant woman. The risk of fetal anomalies can be specified using
      biochemical screening tests such as the triple test. This test substantially
      reduces the number of amniocenteses and proportionally the number of procedure
      related miscarriages. However, disadvantages of the triple test include the
      utility loss of pregnant women who, following a false-negative test result, do
      not undergo amniocentesis and bear a disabled child as well as the intangible
      cost of a false-positive triple test. This paper employs a decision-analytic
      model to reveal the evaluation of this tradeoff, which is implicitly fixed by
      policy recommendations for a direct amniocentesis at maternal age of 35. It then
      determines the optimal level of cutoff risk for the triple test, and derives
      comparative static results: the optimal test accuracy decreases with increasing a
      priori risk and increases with a rise in the miscarriage risk and in the woman's
      preference for detecting an affected fetus as compared to avoiding a miscarriage
      of an unaffected fetus. These results are in contrast to current clinical
      practice, where the cutoff of the triple test usually remains fixed.

PMID- 14570299
TI  - Utilities derived from visual analog scale scores in patients with HIV/AIDS.
AB  - BACKGROUND: Visual analog scale (VAS) scores are used as global quality-of-life
      indicators and, unlike true utilities (which assess the desirability of health
      states v. an external metric), are often collected in HIV-related clinical
      trials. The purpose of this study was to derive and evaluate transformations
      relating aggregate VAS scores to utilities for current health in patients with
      HIV/AIDS. METHODS: HIV-specific transformations were developed using linear and
      nonlinear regression to attain models that best fit mean VAS and standard gamble
      (SG) utility values directly derived from 299 patients with HIV/AIDS
      participating in a multicenter study of health values. The authors evaluated the
      transformations using VAS and SG utility values derived directly from patients in
      other HIV/AIDS studies. Derived transformations were also compared with published
      transformations. RESULTS: A simple linear transformation was derived (u = 0.44v +
      0.49), as was the exponent for a curvilinear model (u = 1 - [1 - v]1.6), where u
      = the sample mean utility and v the sample mean VAS score. The curvilinear
      transformation predicted values within 0.10 of the actual SG utility in 5 of 8
      estimates and within 0.05 in 3 of 8 estimates (absolute error ranged from -0.01
      to +0.21). The linear transformation performed somewhat better, predicting within
      0.10 of the actual SG value in 6 of 8 cases and within 0.05 in 5 of 8 estimates
      (absolute error ranged from -0.05 to +0.13). An alternative linear model (u = v +
      0.018) derived from the literature performed similarly to our linear model (7 of
      8 predictions within 0.10, 1 of 8 estimates within 0.05, and absolute error
      ranging from -0.15 to +0.10), whereas an alternative published curvilinear model
      (u = 1 - [1 - v]2.3) performed the least well (2 of 8 estimates within 0.10 of
      the actual values and no estimates within 0.05). CONCLUSIONS: Predicted utilities
      are a reasonable alternative for use in HIV/AIDS decision analyses and cost
      effectiveness analyses. Linear transformations performed better than curvilinear
      transformations in this context and can be used to convert aggregate VAS scores
      to aggregate SG values in large HIV/AIDS studies that collect VAS data but not
      utilities.

PMID- 14570300
TI  - Effect of assessment method on the discrepancy between judgments of health
      disorders people have and do not have: a web study.
AB  - Three experiments on the World Wide Web asked subjects to rate the severity of
      common health disorders such as acne or arthritis. People who had a disorder
      ("Haves") tended to rate it as less severe than people who did not have it ("Not
      haves"). Two explanations of this Have versus Not-have discrepancy were rejected.
      By one account, people change their reference point when they rate a disorder
      that they have. More precise reference points would, on this account, reduce the
      discrepancy, but, if anything, the discrepancy was larger. By another account,
      people who do not have the disorder focus on attributes that are most affected by
      it, and the discrepancy should decrease when people make ratings on several
      attributes. Again, if anything, the discrepancy increased when ratings were on
      separate attributes (combined by a weighted average). The discrepancy varied in
      size and direction across disorders. Subjects also thought that they would be
      less affected than others.

PMID- 14570301
TI  - Validity of standard gamble utilities as measured by transplant readiness in lung
      transplant candidates.
AB  - PURPOSE: To evaluate the validity of standard gamble (SG) utilities, by comparing
      utilities with decision-making behavior in a group of lung transplant candidates
      facing a risky health decision. METHODS: The authors elicited SG utilities for
      current health from 57 transplant candidates. They assessed the concordance
      between utility scores and patients' self-reported readiness to be placed on the
      transplant waiting list ("listed"). Because transplantation represents a real
      life gamble with a short-term survival probability of 85%, the authors defined
      their minimum validity criterion as utility for current health < or = 0.85 in
      transplant-ready patients. RESULTS: Utilities were significantly higher in
      patients who were not ready for listing (n = 22, median utility = 0.79, range
      0.06-1) than in those who were ready or listed (n = 35, median utility = 0.50,
      range 0-0.85, P < 0.00005). All transplant-ready patients had utilities < or =
      0.85 for current health. CONCLUSIONS: Low SG utilities were associated with
      transplant readiness in this population of lung transplant candidates. These
      results provide one line of evidence supporting the validity of SG utilities as a
      measure of health-related quality of life, using the criterion of decision-making
      behavior.

PMID- 14570302
TI  - The use of gene tests to detect hereditary predisposition to chronic disease: is
      cost-effectiveness analysis relevant?
AB  - Screening for genetic susceptibility provides new opportunities for preventing
      common diseases, but whether such screening will result in substantial costs or
      savings is unclear. Cost-effectiveness analyses (CEAs) provide a theoretical
      framework for guiding clinical decisions about genetic tests. However, CEAs have
      been largely irrelevant in informing policy, clinical decisions, or patient
      demand concerning these genetic tests. Genetic tests have often proceeded
      directly from development and preliminary validation into clinical practice, with
      little understanding of their clinical, economic, and psychosocial implications.
      Using screening for BRCA mutations as an example, the accuracy of the tests and
      the effectiveness of many interventions among those who screen positive remain in
      question. CEAs do not seem to have played an important role in identifying whom
      to offer genetic testing nor how to manage those found to carry the gene marker.
      Credible CEAs are needed to provide guidance about screening decisions.

PMID- 14570303
TI  - Buccal delivery systems.
AB  - The oral cavity is an attractive site for drug delivery due to ease of
      administration and avoidance of possible drug degradation in gastrointestinal
      tract and first-pass metabolism. Buccal drug delivery specifically refers to the
      delivery of drugs within/ through buccal mucosa to affect local/systemic
      pharmacological actions. This review briefly describes advantages and limitations
      of buccal drug delivery, anatomical structure of oral mucosa, and methodology in
      evaluating buccal drug delivery system, focusing on physiology, pharmacology,
      pathology, and formulation design in line with recent developments in buccal
      delivery systems.

PMID- 14570304
TI  - Dissolution and absorption modeling: model expansion to simulate the effects of
      precipitation, water absorption, longitudinally changing intestinal permeability,
      and controlled release on drug absorption.
AB  - A previously described model for simulating drug dissolution, absorption, and
      pharmacokinetics has been expanded beyond the original application of simulating
      immediate-release dosage forms to include simulation of drug precipitation, water
      absorption from the gastrointestinal tract, changing gastrointestinal
      permeability, disintegration, and controlled-release and dissolution from a GITS
      type dosage form. A mathematical description of the model is presented as well as
      a retrospective analysis of nifedipine to demonstrate the utility of the model.
      The fourth-order Runge-Kutta numerical method was used to solve the series of
      coupled differential equations used to simulate the process of dissolution,
      absorption, and drug disposition. The model was able to simulate the clinically
      demonstrated effect for drug particle size on nifedipine plasma concentrations
      for an immediate-release dosage form. Further simulations indicated that drug
      particle size was less important for a GITS-type dosage form at a release rate of
      1.7 mg/hr compared to rate of 17 mg/hr. Hypothetical calculations simulated the
      potential effect of drug precipitation, water absorption, and changing
      permeability on drug plasma concentrations. The expanded model increases the
      utility of a previously described model in providing guidance in drug development
      and selection.

PMID- 14570305
TI  - Acrylic matrix type nicotine transdermal patches: in vitro evaluations and batch
      to-batch uniformity.
AB  - Nicotine transdermal patches (NTPs) were fabricated using an acrylic pressure
      sensitive adhesive emulsion to form a transparent matrix film. An automated thin
      layer chromatography (TLC) plate scraper was used to control the thickness of the
      cast nicotine matrix film. The in vitro release behavior and permeation of
      nicotine across abdominal human epidermis (HE) from the NTPs was studied using
      United States Pharmacopeia (USP) dissolution apparatus 5 (paddle over disk) and
      modified Franz-diffusion cell, respectively. The release of nicotine from the
      NTPs showed a good linear correlation with the square root of time (R2 > 0.99).
      This indicated a matrix diffusion controlled-release mechanism. The surface
      morphology of the matrix of the NTP was uniform and nonporous before and after
      release, indicating that the dried adhesive nicotine matrix was a homogeneous
      single-phase film. Neither the nicotine content in the range 4.70-8.41% w/w nor
      the film thicknesses of the NTPs affected the apparent diffusion coefficient of
      nicotine in the acrylic matrix. A good relationship between the amount of
      nicotine permeated across the HE and the square root of time was also observed
      with R2 > 0.98. This study also showed that the NTPs provided a good delivery
      system with more than 65% of the nicotine delivery being controlled by the
      device. Moreover, the release of nicotine from six production batches met the
      criteria of USP 24. This finding presented a good potential of this method for
      upscaling to industrial manufacturing.

PMID- 14570306
TI  - Nimesulide-modified gum karaya solid mixtures: preparation, characterization, and
      formulation development.
AB  - Solid mixtures of nimesulide (NS) and modified gum karaya (MGK) were prepared to
      improve the dissolution rate of NS. The effect of drug-carrier ratio on
      dissolution rate of NS was investigated by preparing the solid mixtures of
      different ratios by cogrinding method. Solid mixtures were also prepared by
      physical mixing, kneading, and solid dispersion techniques to study the influence
      of method of preparation. Differential Scanning Calorimetry (DSC), X-ray
      Diffraction (XRD), and equilibrium solubility studies were performed to explain
      the results of in vitro dissolution rate studies. It was clearly evident from the
      results that the NS dissolution rate was dependent on the concentration of MGK in
      the solid mixtures, and optimum weight ratio was found to be 1:4 (NS:MGK). Though
      the dissolution rate of NS from all solid mixtures prepared by different methods
      improved significantly, maximum improvement in dissolution rate was observed with
      solid dispersions. The order of methods basing on their effect on dissolution
      efficiency is solid dispersion > kneading > cogrinding > physical mixing > pure
      NS. Tablets of pure drug and solid mixtures (1:4 w/w, NS:MGK) were prepared.
      Though the best results from the dissolution test were obtained for the tablets
      containing solid dispersions, tablets containing cogrinding mixture were found to
      be suitable, from a practical point of view, for commercialization.

PMID- 14570307
TI  - Influence of the metering chamber volume and actuator design on the aerodynamic
      particle size of a metered dose inhaler.
AB  - Presented in this work are the results of a study designed to investigate the
      impact of the valve metering chamber volume and actuator design on the
      aerodynamic particle size distribution (PSD) of a suspension metered dose inhaler
      (MDI) containing propellant HFA-227. It was hypothesized that the valve metering
      volume and the actuator design in the MDI could influence the PSD of the emitted
      dose since it would affect the aerosol spray dynamics. The PSD results from this
      study, measured using cascade impaction, revealed that samples containing an
      actuator intended for oral delivery (rectangular mouthpiece and orifice diameter
      of approximately 0.5 mm) produced a higher fine particle dose (FPD) than those
      containing an actuator intended for nasal delivery (circular nosetip and orifice
      diameter of approximately 1 mm). In addition, the drug PSD profile was shown to
      be more sensitive to differences in the particle size of the suspended material
      when the oral actuator was used compared to when the nasal actuator was used. The
      valve metering chamber (25 vs. 63 microL volume) did not appear to have a major
      effect on the product aerodynamic PSD or the droplet size. These results
      demonstrate the importance of actuator design and orifice size in determining the
      aerodynamic PSD of an MDI.

PMID- 14570308
TI  - Evaluation of the film-forming property of hydrogenated rosin.
AB  - The film-forming and coating properties of a new biomaterial, hydrogenated rosin
      (HR), is investigated in the present communication. Films produced by casting
      method are studied for mechanical, (tensile strength, elongation, and Young's
      modulus), water vapor transmission, and moisture absorption characteristics. Type
      of plasticizer and its concentration were observed to play an important role in
      modifying the film characteristics. Dibutyl sebacate (DBS), a hydrophobic
      plasticizer, was found to be suitable for development of flexible and smooth
      films. Film formulations plasticized with DBS were investigated for coating the
      drug layered nonpareil seeds where plasticization facilitated development of
      smooth and uniformly coated pellets. The increase in coat buildup, however, did
      not sustain the drug release significantly. The studies conclude that HR films
      promise utility as moisture-protective hydrophobic, film-coating materials.

PMID- 14570309
TI  - Effect of lipid excipients on in vitro pancreatic lipase activity.
AB  - PURPOSE: To study the effects of two lipid excipients, Peceol and Gelucire 44/14
      on the in vitro pancreatic lipase activity. METHODS: A 50 microL reaction
      mixture, consisting of 45 microL (3H) triolein as the radiolabeled substrate, 2.5
      microL Peceol or Gelucire 44/14 (0.05-0.5%), either alone or in combination, 2.5
      microL colipase (100 microg/mL), and 2.5 microL pancreatic lipase (1 mg/mL), was
      incubated for 10 min at room temperature. At the end of incubation, the reaction
      was stopped by the addition of an extraction solvent containing chloroform,
      methanol, and n-heptane (12.5:14:10), and the mixture vortexed briefly.
      Subsequently, 250 microL of 50 mM sodium carbonate was added and the aqueous and
      organic phase separated by centrifugation for 5 min at 1000 g. One hundred
      microliters of the supernatant was transferred to a scintillation counter and
      then radioactivity measured after the addition of 3.6 mL of scintillation fluid.
      Pancreatic lipase activity was determined by measuring the amount of free fatty
      acid released into the incubation medium and expressed as micromol free fatty
      acid released/min. RESULTS: When used alone, Peceol inhibited the pancreatic
      lipase activity significantly in a concentration-dependent manner, with a maximum
      inhibition of 57% at 0.4% of the excipient [p < 0.05, one-way analysis of
      variance (ANOVA)]. Similarly, Gelucire 44/14 alone caused inhibition of lipase
      activity in a concentration-dependent manner. However, the maximum inhibition
      (30%) was smaller in magnitude compared with the former agent. When the two
      excipients were used in combination, the inhibitory effects on the enzyme
      activity were similar to those observed with the individual agents (p < 0.05, one
      way ANOVA). However, the maximum inhibition of 30% was lower than that observed
      with Peceol alone. CONCLUSIONS: The results from this study suggest that these
      lipid excipients inhibit in vitro pancreatic lipase activity and should be taken
      into consideration when developing oral formulations using these agents.

PMID- 14570310
TI  - Different dissolution media lead to different crystal structures of talinolol
      with impact on its dissolution and solubility.
AB  - During the performance of dissolution tests with immediate and controlled-release
      talinolol tablets it was detected that the type of the buffer used as dissolution
      medium had a strong influence on the solubility and the dissolution behavior of
      the drug. It was proven that talinolol appeared in different crystal structures
      with strongly differing solubilities when pure water, acetate, or phosphate
      buffers were employed as dissolution media. The resulting crystal structures were
      characterized by means of light microscopy, differential scanning calorimetry,
      and X-ray powder diffraction. All methods were adjuvant to detect changes in
      talinolol crystal structures. The different solubility and dissolution properties
      of the talinolol salts or modifications may be viewed as a source for its
      incomplete and variable bioavailability. Furthermore, the food effect, described
      in the literature, that leads to a decrease in talinolol absorption, could be due
      to changes in the composition of gastrointestinal fluids leading to different
      talinolol crystal structures. Furthermore, it was detected that the addition of
      sodium chloride increases talinolol solubility and accelerates its dissolution
      from controlled-release tablets at concentrations between 0% and 1.25%, while an
      addition of sodium dodecylsulfate (SDS) as surfactant only had a solubility
      improving effect at concentrations > 0.75%. At lower concentrations SDS decreased
      the solubility of talinolol and notably decelerated its release from controlled
      release tablets.

PMID- 14570311
TI  - Potential use of cyclodextrins to enhance the solubility of YM466 in aqueous
      solution.
AB  - Various solubilizing agents for YM466, a new Factor Xa inhibitor, were
      investigated to begin designing the aqueous formulation for subcutaneous
      administration. The tentative target concentration was 5 mg/mL. First, three
      kinds of buffer solutions (glycine-HCl, citrate, and lactate) were examined for
      their solubilizing effects. The dissolution rate of YM466 in lactate buffer was
      the fastest, as determined by visual examination at room temperature. The
      dissolution rate of YM466 in lactate buffer was enhanced, without degradation, by
      heating at 40 degrees C, and YM466 solution at a concentration of 1 mg/mL became
      transparent 10 min after the start of heating. The solubility of YM466 increased
      along with lactate concentrations ranging from 50 mM to 200 mM and reached a high
      of 1.3 mg/mL after increasing lactate concentration to 200 mM at 5 degrees C. The
      addition of cyclodextrins beta-cyclodextrin (beta-CD), 2-hydroxypropyl-beta
      cyclodextrin (HP-beta-CD), and gamma-cyclodextrin (gamma-CD), but not alpha
      cyclodextrin (alpha-CD), had remarkable impact on its solubility, and 7-8 mg/mL
      of YM466 was dissolved by the addition of HP-beta-CD or gamma-CD. These results
      demonstrated that YM466 was included in cyclodextrins and that the inclusion
      formations required a cavity size larger than alpha-CD. Based on the calculation
      from the linear portion of the phase solubility diagrams, apparent stability
      constants of alpha-CD, beta-CD, HP-beta-CD, and gamma-CD at 5 degrees C were
      estimated to be 2M(-1), 206M(-1), 143M(-1), and 276M(-1), respectively.
      Therefore, we found that gamma-CD has the largest inclusion capacity.

PMID- 14570312
TI  - The influence of polymeric subcoats and pellet formulation on the release of
      chlorpheniramine maleate from enteric coated pellets.
AB  - The influences of aqueous polymeric subcoats and pellet composition on the
      release properties of a highly water-soluble drug, chlorpheniramine maleate
      (CPM), from enteric coated pellets were investigated. Three different aqueous
      polymeric subcoats, Eudragit RD 100, Eudragit RS 30D, and Opadry AMB, were
      applied to 10% w/w CPM-loaded pellets that were then enteric coated with Eudragit
      L 30D-55. Observed drug release from the coated pellets in acidic media
      correlated with water vapor transmission rates derived for the subcoat films. The
      influence of pellet composition on retarding the release of CPM from enteric
      coated pellets in 0.1 N HCl was investigated. The rate of drug release was
      greatest for pellets prepared with lactose, microcrystalline cellulose, or
      dibasic calcium phosphate compared with pellets formulated with citric acid and
      microcrystalline cellulose. Citric acid reduced the pellet micro-environmental
      pH, decreasing the amount of drug leakage in 0.1 N HCL during the first 2 hr of
      dissolution. Polymer flocculation was observed when CPM was added to the Eudragit
      L 30D-55 dispersion. An adsorption isotherm was generated for mixtures of CPM and
      the polymer and the data were found to fit the Freundlich model for adsorption.
      Adsorption of CPM to the polymer decreased with the addition of citric acid to
      the drug-polymer mixtures.

PMID- 14570313
TI  - Pharmaceutical applications of shellac: moisture-protective and taste-masking
      coatings and extended-release matrix tablets.
AB  - Shellac is a natural polymer, which is used as enteric coating material in
      pharmaceutical applications. The major objective of the present study was to
      investigate the potential of shellac for other purposes, namely to provide
      moisture-protective and taste-masking coatings as well as extended-release matrix
      tablets. The efficiency of shellac to achieve moisture protection and taste
      masking was compared with that of hydroxypropyl methylcellulose (HPMC), which is
      most frequently used for these purposes. Shellac-coated tablets showed lower
      water uptake rates than HPMC-coated systems at the same coating level. The
      stability of acetylsalicylic acid was higher in tablets coated with shellac
      compared with HPMC-coated systems, irrespective of the storage humidity.
      Therefore, lower shellac coating levels were required to achieve the same degree
      of drug protection. Shellac coatings effectively masked the unpleasant taste of
      acetaminophen tablets. Compared to HPMC, again lower coating levels were required
      to achieve similar effects. The resulting drug release in simulated gastric fluid
      was not significantly altered by the thin shellac coatings, which rapidly
      ruptured due to the swelling of the coated tablet core. In addition, shellac was
      found to be a suitable matrix former for extended-release tablets. The latter
      could be prepared by direct compression or via wet granulation using ethanolic or
      ammoniated aqueous shellac binder solutions. The resulting drug-release patterns
      could effectively be altered by varying different formulation and processing
      parameters.

PMID- 14570314
TI  - Comparison of different chloroformates for the derivatisation of seleno amino
      acids for gas chromatographic analysis.
AB  - Three chloroformate reagents, ethyl chloroformate (ECF), methyl chloroformate
      (MCF) and menthyl chloroformate (MenCF), have been used for the derivatisation of
      seleno amino acids and their performance was compared. Chromatographic parameters
      and the inertness of the different instrumental configurations used (gas
      chromatography-atomic emission detection (GC-AED), and GC-MS) were shown to have
      a significant influence on the detection of various seleno amino acids
      (selenomethione, selenoethione and selenocysteine) and some sulphur-containing
      amino acids (methionine, cysteine, cystine and methylcysteine) which were
      included in the experiments for comparison. Methyl chloroformate was the
      preferred derivatisation reagent, since it generally performed best in terms of
      derivatisation yield and reproducibility and also showed less significant
      conditioning effects than ethyl chloroformate. Methyl and ethyl chloroformate
      derivatives of selenomethionine, selenoethionine, cysteine and methionine were
      detectable, while the detection of the menthyl chloroformate derivatives of
      selenocystine and cystine was not reproducible. Overall efficiencies for the
      determination of selenomethionine and selenoethionine from aqueous extracts
      ranged from 40 to 100% for methyl chloroformate, over 30-75% for ethyl
      chloroformate to 15-70% for menthyl chloroformate for different series measured
      over a period of months. The relative standard deviation of the method for the
      methyl and menthyl chloroformate derivatisation ranged from 7 to 13% without
      internal standard and was improved to 2% for the determination of
      selenomethionine using selenoethionine as internal standard. This indicates that,
      despite the limited reproducibility of the method, its repeatability is good
      enough to allow accurate determination of seleno amino acids, which was also
      demonstrated by the analysis of selenium supplementation tablets for human diet
      that contained selenomethionine.

PMID- 14570315
TI  - Application of polyphenylmethylsiloxane coated fiber for solid-phase
      microextraction combined with microwave-assisted extraction for the determination
      of organochlorine pesticides in Chinese teas.
AB  - Polyphenylmethylsiloxane (PPMS) as a novel coating for solid-phase
      microextraction (SPME) combined with microwave-assisted extraction (MAE) has been
      applied to determine the concentrations of organochlorine pesticides (OCPs) in
      Chinese teas. The characteristics of PPMS fiber, the extraction modes of SPME,
      the extraction time, temperature, and salt effects were investigated. Microwave
      irradiation time and power were also studied. Compared with commercial
      polydimethylsiloxane (PDMS) fiber and homemade sol-gel polymethylsiloxane (PMS)
      fiber, the novel porous sol-gel PPMS fiber exhibited high sensitivity and
      selectivity for OCPs compounds, higher thermal stability (to 350 degrees C) and
      long service life (more than 150 times). The recoveries of MAE is compared with
      that of ultrasonic extraction (USE), MAE-SPME-gas chromatography (GC)/electron
      capture detection (ECD) methods showed better results for Chinese teas. Linear
      ranges of OCPs in the blank green tea was 0.1-10(3) ng/l. Detection limits of
      this method are below 0.081 ng/l. Recoveries of this method are between 39.05 and
      94.35%. The repeatability of the technique was less than 16% relative standard
      deviation (R.S.D.). The tested pesticides in three Chinese teas were at the ng/g
      level.

PMID- 14570316
TI  - Pyrrole-based conductive polymer as the solid-phase extraction medium for the
      preconcentration of environmental pollutants in water samples followed by gas
      chromatography with flame ionization and mass spectrometry detection.
AB  - A pyrrole-based polymer was synthesized and applied as a new sorbent for solid
      phase extraction (SPE) of some environmental pollutants from water samples.
      Polypyrrole (PPy) was synthesized by chemical oxidation of the monomer in
      nonaqueous solution. SPE of selected phenols, pesticides, and polyaromatic
      hydrocarbons (PAHs) from aqueous samples were performed using 200 mg PPy. The
      determination was subsequently carried out by gas chromatography-flame ionization
      detection (GC-FID) and gas chromatography-mass spectrometry (GC-MS). The polymer
      showed much higher recoveries for aromatic compounds than aliphatics.
      Preconcentration of sample volumes up 11 led to acceptable recoveries for
      aromatic and other tested polar compounds. The R.S.D. for a river water sample
      spiked with phenols, pesticides and PAHs at sub-ppb level was lower than 10% (n =
      3) and limits of detection for these compounds were between 15 and 120 ng l(-1).

PMID- 14570317
TI  - Martin's rule revisited. Its molecular sense and limitations.
AB  - The linear relation ln k' = Bn + ln A between the retention factor k' in liquid
      adsorption chromatography (LAC) and the number of repeat units n within a
      homologous series of oligomers is called Martin's rule. This empirical relation
      was supported by the retention behavior of the homologous series of different
      classes of oligomers but had no theoretical justification. In this paper, it is
      demonstrated that Martin's rule is a consequence of the general theory of liquid
      chromatography and the molecular sense of coefficients B and A is clarified: B is
      the Gibbs energy of the repeat unit of the long polymer chain adsorbed at the
      wall surface, and A is a combination different parameters which characterize the
      column and the adsorption correlation length H. The theory predicts the
      deviations from the linear dependence under conditions of weak adsorption between
      repeat units and stationary phase when H is close to radius of gyration Rg.
      Experimental data for retention volumes and selectivity of poly(ethylene glycol)s
      are given for normal and reversed-phase LAC on different columns in acetone-water
      and methanol-water as mobile phases. These data show excellent agreement between
      the theory and experiments. It is shown that Martin's rule holds under special
      conditions, which are theoretically defined by the relation H > Rg/1.5.

PMID- 14570318
TI  - Pressure-induced effects in the heterogeneous adsorption of insulin on
      chromatographic surfaces.
AB  - The effect of increasing the average column pressure (ACP) on the heterogeneous
      adsorption of insulin variants on a C18-bonded silica was studied in isocratic
      reversed-phase HPLC. Adsorption isotherm data of lispro and porcine insulin
      obtained for values of the ACP ranging from 57 to 237 bar were fitted to the
      Langmuir-Freundlich and the Toth equation. The resulting isotherm parameters,
      including the equilibrium adsorption constant and the heterogeneity index, were
      next used for the calculation of distribution functions characterizing the energy
      of interactions between the adsorbed insulin molecules and the stationary phase.
      It was observed that increasing the pressure by 180 bar causes a broadening of
      the distribution functions and a shift of the position of their maximum toward
      lower interaction energies. These findings suggest that, under high pressures,
      the insulin molecules interact with the stationary phase in a more diversified
      way than under low pressures. Additionally, the most probable value of the energy
      of the insulin-surface interactions becomes lower when the ACP increases. The
      pressure-induced changes in the interaction of insulin variants with the
      hydrophobic surface are attributed to a possible conformational flexibility of
      the molecular structure of this protein.

PMID- 14570319
TI  - Slow equilibration of reversed-phase columns for the separation of ionized
      solutes.
AB  - Reversed-phase columns that have been stored in buffer-free solvents can exhibit
      pronounced retention-time drift when buffered, low-pH mobile phases are used with
      ionized solutes. Whereas non-ionized compounds exhibit constant retention times
      within 20 min of the beginning of mobile phase flow, the retention of ionized
      compounds can continue to change (by 20% or more) for several hours. If mobile
      phase pH is changed from low to high and back again, an even longer time may be
      required before the column reaches equilibration at low pH. The speed of column
      equilibration for ionized solutes can vary significantly among different reversed
      phase columns and is not affected by flow rate.

PMID- 14570320
TI  - Terpyridine-based silica supports prepared by ring-opening metathesis
      polymerization for the selective extraction of noble metals.
AB  - The synthesis of a terpyridine-based sorbent for solid-phase extraction (SPE) of
      noble metal ions is described. For this purpose, 4'-(norborn-2-en-5
      ylmethylenoxy)terpyridine was copolymerized with norborn-2-ene via Mo(N-2,6-i-Pr2
      C6H3)(=CHCMe2Ph) (OC(CH3)(CF3)2)2-catalyzed ring-opening metathesis
      polymerization (ROMP) to give a poly(norbornene900(-b-4'-(norborn-2-en-5
      ylmethylenoxy)terpyridine60) block-copolymer. This block-copolymer was used for
      the preparation of polymer-coated silica 60 (4.8 wt.% coating), which was
      investigated for its extraction capabilities for Cr(III), Mn(II), Re(II),
      Fe(III), Ru(III), Co(II), Rh(III), Ir(III), Ni(II), Pd(II), Pt(II), Cu(II),
      Ag(I), Au(III), Zn(II), Cd(II) and Hg(II), at different pH. Under competitive
      conditions and at pH < 0.6, the selectivity order was Pd approximately = Ag
      approximately = Au approximately = Pt > Re > Ir > Rh > Ru > Fe > Cr approximately
      = Mn approximately = Cd approximately = Zn. Enhanced selectivity was observed at
      pH = 3.5, the order was Au > Hg > Pd approximately = Ag > Rh > Pt > Ir
      approximately = Re > Cu > Co approximately = Zn approximately = Cd approximately
      = Ni > Cr > Mn. The maximum metal loading that was achieved under non-competitive
      conditions was > 6 mg/g for Au(III), Hg(II), Pd(II) and Ag(I). Even under
      competitive conditions, loadings of > 6 mg/g were realized for Au(III) and
      Hg(II). Quantitative recoveries > 97% were observed for all metals in case
      loading was stopped before reaching the point of breakthrough.

PMID- 14570321
TI  - Comparison of the binary equilibrium isotherms of the 1-indanol enantiomers on
      three high-performance liquid chromatography columns of different sizes.
AB  - The competitive isotherm data for the enantiomers of 1-indanol were measured on
      three columns, a microbore column (15 cm x 0.1 cm), a conventional analytical
      column (15 cm x 0.46 cm), and a semi-preparative column (20 cm x 1.0 cm), packed
      with Chiralcel OB. The sets of isotherm data measured on each one of these three
      columns could be fitted well by a bi-Langmuir isotherm model. The experimental
      elution band profiles of mixtures of the 1-indanol isomers were recorded on the
      three columns. The isotherm model, combined with the equilibrium dispersive model
      of chromatography, gave calculated profiles that are in excellent agreement with
      the experimental profiles in all cases investigated. It was found that the value
      of the inner diameter of the column is an important parameter in the calculation
      of the isotherm parameters from the measured isotherm data. In order to use
      isotherm data obtained on one column to account for the phase equilibrium on
      another one, the inner diameters of these columns must be measured accurately.
      The diameters of the three columns were all slightly off their nominal value.
      Without correction, an important systematic error was made on the isotherm data
      obtained with the microbore column while only negligible errors were made on the
      data obtained with the other two columns. After due correction for this effect,
      the relative difference between the isotherm data for the microbore and the semi
      preparative column is still, on the average, about 10%, a difference that might
      be explained by the limited precision of the measurement of the microbore column
      diameter. The relative difference between the isotherm data for the analytical
      and the semi-preparative columns was about 1%, a reasonable value, since the two
      columns came from different batches of the same packing material.

PMID- 14570322
TI  - Evaluation of the two-dimensional reversed-phase-reversed-phase separations of
      low-molecular mass polystyrenes.
AB  - The resolving power of four reversed-phase-reversed-phase two-dimensional (2D)
      chromatographic systems was evaluated using information theory (IT) and a
      geometric approach to factor analysis. The first separation dimension employed a
      C18 column, while the second separation dimension employed a carbon clad zirconia
      column. Mobile phases in each dimension were either methanol or acetonitrile. The
      sample matrix that was employed in this study contained a mixture of 58
      components, comprised of stereoisomers and structural isomers of a systematic
      variation in molecular weight. Each of the components were oligostyrenes, with
      between two and five configurational repeating units having either n-butyl, sec
      butyl or tert-butyl end groups. In the two-dimensional systems employed in this
      study, between 46 and 49 of the 58 components could be separated, depending on
      the mobile phase combinations--with apparent resolution that could not possibly
      be achieved in a single one-dimensional separation. The results from this study
      indicate that in order to fully evaluate the resolving power of a 2D system
      multiple methods of analysis that evaluate the separation potential are most
      appropriate. This becomes increasingly important when the sample contains
      components that are very closely related and the retention of solutes displays a
      high degree of solute crowding.

PMID- 14570323
TI  - Effects of alcohol mobile-phase modifiers on the structure and chiral selectivity
      of amylose tris(3,5-dimethylphenylcarbamate) chiral stationary phase.
AB  - Following a previous publication, the present paper reports additional results on
      the effects of alcohol mobile-phase modifiers on the structure and chiral
      selectivity of amylose tris(3,5-dimethylphenylcarbamate) (Chiralpak AD) chiral
      stationary phase (CSP). Solid-state NMR (1H/13C CPMAS) was utilized to identify
      and compare structural differences in Chiralpak AD caused by the various alcohol
      mobile-phase modifiers, many of which were not studied in the previous
      publication. The influences of the various alcohol modifiers (in hexane-based
      mobile phase) on the structure and chiral selectivity of the CSP were studied and
      compared. CPMAS spectra of Chiralpak AD flushed with the mobile phases displayed
      clear evidence of solvent incorporation into the CSP. When alcohol modifiers with
      varying size and bulkiness were used in the mobile phase, differences in
      structure and chiral selectivity were observed on Chiralpak AD based on solid
      state NMR and chromatographic data. The change of t-butanol concentration in the
      t-butanol/hexane mobile phase caused changes of structure and chiral selectivity
      of the Chiralpak AD. These data further support our belief that the different
      chiral selectivities of the CSP associated with the use of different alcohol
      modifiers are due to different alterations of the steric environment of the
      chiral cavities in the CSP by the different mobile-phase modifiers.

PMID- 14570324
TI  - Detection and quantification of bovine, ovine and caprine milk percentages in
      protected denomination of origin cheeses by reversed-phase high-performance
      liquid chromatography of beta-lactoglobulins.
AB  - A method for detecting and quantifying bovine, ovine and caprine milk mixtures in
      milk and cheeses by means of reversed-phase high-performance liquid
      chromatography (RP-HPLC) of beta-lactoglobulins is described. Gradient elution
      was carried out with a flow rate of 0.5 ml/min and a temperature of 45 degrees C,
      using a mixture of two solvents: solvent A (0.1% TFA in water) and solvent B
      (0.09% TFA in 80% aqueous acetonitrile, v/v). The effluent was monitored at 215
      nm. Under the conditions used different chromatographic patterns were obtained
      for bovine, ovine and caprine whey proteins. Each milk type presented different
      retention times for beta-lactoglobulin peaks. Binary mixtures of bovine and ovine
      or bovine and caprine raw milks containing 1, 2, 5, 10, 20, 30, 50, 75 and 95%
      (v/v) of bovine milk, as well as ovine and caprine milk mixtures containing 1, 2,
      5, 10, 20, 30, 50, 75 and 95% (v/v) of ovine milk were used for cheese making.
      Cheeses were prepared and ripened, according to traditional methods. Milk
      mixtures, fresh and ripened cheeses were analyzed. A linear relationship was
      established between log 10 of beta-lactoglobulin peaks ratio (calculated as peak
      area values ratio) and log 10 of the relative percentage of bovine or ovine milk.
      The ratio between beta-lactoglobulin peaks was not affected by the degree of
      ripening. Thus, enabling the quantification of milk type percentage, with a
      detection limit of 2%. This technique allowed quantification of milk species
      within the concentration range of 5-95%. The method was successfully applied for
      authenticity evaluation and quantitative determination of ovine and caprine milk
      percentages of commercial protected denomination of origin (PDO) cheeses.

PMID- 14570325
TI  - Determination of polar organophosphorus pesticides in vegetables and fruits using
      liquid chromatography with tandem mass spectrometry: selection of extraction
      solvent.
AB  - A method based on liquid chromatography (LC)-mass spectrometry (MS)/MS was
      developed for sensitive determination of a number of less gas chromatography (GC)
      amenable organophosphorus pesticides (OPs; acephate, methamidophos,
      monocrotophos, omethoate, oxydemeton-methyl and vamidothion) in cabbage and
      grapes. For extraction, several solvents were evaluated with respect to the
      possibility of direct injection, matrix-induced suppression or enhancement of
      response, and extraction efficiency. Overall, ethyl acetate was the most
      favourable solvent for extraction, although a solvent switch was required. For
      some pesticide/matrix combinations, reconstitution of the residue after
      evaporation required special attention. Extracts were analysed on a C18 column
      with polar endcapping. The pesticides were ionised using atmospheric pressure
      chemical ionisation on a tandem mass spectrometer in multiple reaction monitoring
      mode. The final method is straightforward and involves extraction with ethyl
      acetate and a solvent switch to 0.1% acetic acid/water without further cleanup.
      The method was validated at the 0.01 and 0.5 mg/kg level, for both cabbage and
      grapes. Recoveries were between 80 and 101% with R.S.D. < 11% (n = 5). The limit
      of quantification was 0.01 mg/kg and limits of detection were between 0.001 and
      0.004 mg/kg.

PMID- 14570326
TI  - Determination of selected human pharmaceutical compounds in effluent and surface
      water samples by high-performance liquid chromatography-electrospray tandem mass
      spectrometry.
AB  - A simple method is presented for the analysis of 13 pharmaceutical and
      pharmaceutical metabolite compounds in sewage effluents and surface waters. The
      pharmaceutical compounds were extracted using a genetic solid-phase extraction
      (SPE) procedure using Phenomenex Strata X as a stationary phase. Extracts were
      quantitatively analysed by four separate reversed-phase high-performance liquid
      chromatography-electrospray tandem mass spectrometry (HPLC-ESI-MS/MS) techniques
      and quantified by comparison with an internal standard ([13C]-phenacetin).
      Recoveries and limits of detection (LOD) for sulfamethoxazole (120%, 50 ng l(
      1)), acetyl-sulfamethoxazole (56%, 50 ng l(-1)), trimethoprim (123%, 10 ng l(
      1)), erythromycin (73%, 10 ng l(-1)), paracetamol (75%, 50 ng l(-1)), ibuprofen
      (117%, 20 ng l(-1)), clofibric acid (83%, 50 ng l(-1)), mefenamic acid (24%, 50
      ng l(-1)), diclofenac (62%, 20 ng l(-1)), propranolol (45%, 10 ng l(-1)),
      dextropropoxyphene (63%, 20 ng l(-1)) and tamoxifen (42%, 10 ng l(-1)) were all
      acceptable. The recovery of lofepramine (4%) was too low to be of use in a
      monitoring programme. Application of the method to samples collected from UK
      sewage effluents and surface waters showed detectable concentrations of mefenamic
      acid, diclofenac, propranolol, erythromycin, trimethoprim and acetyl
      sulfamethoxazole in both matrices. Ibuprofen and dextropropoxyphene were detected
      in sewage effluents alone. All other pharmaceutical compounds were below the
      methods limits of detection.

PMID- 14570327
TI  - Analysis of aldehydes in water by solid-phase microextraction with on-fiber
      derivatization.
AB  - The solid-phase microextraction (SPME) technique with on-fiber derivatization was
      evaluated for the analysis of aldehydes in water. The
      poly(dimethylsiloxane)/divinylbenzene (PDMS/DVB) fiber was used and O-2,3,4,5,6
      (pentafluorobenzyl)hydroxylamine hydrochloride (PFBHA) were first loaded onto the
      fiber. The aldehydes in water sample were agitated into headspace and extracted
      by SPME with on-fiber derivatization. Gas chromatography/mass spectrometry
      (GC/MS) was used for the analysis of oximes formed and the adsorption-time
      profiles were examined. The precision, recovery and method detection limits
      (MDLs) were evaluated with spiked bidistilled water, chlorinated tap water as
      well as well water. The relative standard deviations from different spiked water
      sample were all less than 10% and the recoveries were 100 +/- 15%. With 2 ml of
      water sample, MDLs were in the range of 0.12-0.34 microg/l. Compared with other
      techniques, the study shown here provided a simple, fast and reliable method for
      the analysis of aldehydes in water.

PMID- 14570328
TI  - Identification of fatty acids in gas chromatography by application of different
      temperature and pressure programs on a single capillary column.
AB  - A method for the identification of fatty acid methyl esters (FAME) based on the
      analysis of shifts in equivalent chain lengths (ECL) is described. The method is
      based on two-dimensional retention data achieved on one capillary column. Various
      temperature and pressure programs are applied on the same cyanopropyl column and
      the shifts in the ECL values are analysed by multivariate methods. The chain
      length, number of double bonds, and the double bond positions can be determined
      with high accuracy. The same procedure is suitable for determination of the
      number of trans and cis double bonds in trans fatty acids, and for detection of
      artefacts in fatty acid methyl ester chromatograms.

PMID- 14570329
TI  - Evaluation of analyte protectants to improve gas chromatographic analysis of
      pesticides.
AB  - A common problem in gas chromatography (GC) applications is the analyte losses
      and/or peak tailing due to undesired interactions with active sites in the inlet
      and column. Analytes that give poor peak shapes or degrade have higher detection
      limits, are more difficult to identify and integrate, and are more prone to
      interferences than stable analytes that give narrow peaks. For susceptible
      analytes, significant peak quality improvements are obtained when matrix
      components are present because they fill active sites, thus reducing analyte
      interactions. This phenomenon is called "matrix-induced chromatographic response
      enhancement." Several approaches have been proposed to minimize peak distortion
      phenomena and compensate for matrix-induced effects, which is especially
      important for accurate quantitation, but each approach has serious limitations
      for routine multi-pesticide analysis. In this study, we demonstrate the
      feasibility of using "analyte protectants" to provide a more convenient and
      effective solution to the problem than other approaches developed thus far. The
      protecting agents are added to extracts and matrix-free standards alike to
      provide the chromatographic enhancement effect even for the most susceptible
      analytes in a very dirty GC system. In this study, we evaluated 93 different
      compounds to find the most suitable ones for improving chromatographic quality of
      the signal. Because hydrogen bonding has been shown to be an important factor in
      analyte interactions with active sites, we mainly focused on additives with
      strong hydrogen bonding capabilities. Dramatic peak enhancements were achieved
      using compounds containing multiple hydroxy groups, such as sugars and sugar
      derivatives, and gulonolactone appears to be the most effective protecting agent
      for the most pesticides that we tested. The benefits of using analyte protectants
      versus alternative procedures for overcoming matrix-induced effects in
      quantitation include: (a) simpler procedure; (b) easier integration of peaks; (c)
      lower detection limits; (d) better quantitation; (e) less maintenance of the GC
      inlet; and (e) lower cost. However, long-term influences on the performance of
      the chromatographic system have yet to be established.

PMID- 14570330
TI  - Multiresidue method for determination of 90 pesticides in fresh fruits and
      vegetables using solid-phase extraction and gas chromatography-mass spectrometry.
AB  - A multiresidue method for analysis of 90 pesticides with different physico
      chemical properties in fruits and vegetables was developed. The method involves a
      rapid and small-scale extraction procedure with acetone using vortex mixing.
      Solid-phase extraction (SPE) on a highly cross-linked polystyrene divinylbenzene
      column (LiChrolut EN) was used for clean-up and pre-concentration of the
      pesticides from the water-diluted acetone extracts. For most fruit and vegetable
      samples this partial clean-up was sufficient, but some of them with more co
      extracting substances need further clean-up (cereals, spinach, carrots, etc.).
      Diethylaminopropyl (DEA) modified silica was used for efficient removal of
      interferences caused by various organic acids, sugars, etc. The pesticide
      residues were determined by gas chromatography with a mass selective detector (GC
      MS). The majority of pesticide recoveries for various fruits and vegetables were
      >80% in the concentration range from 0.01 to 0.50 mg/kg, except for the most
      polar pesticides (methamidophos, acephate, omethoate) which cannot be determined
      by this method. The limit of quantitation for most of the pesticides was 0.01
      mg/kg with majority of relative standard deviations (R.S.D.s) below 10%.

PMID- 14570331
TI  - Classical approach to interpretation of the charge-dependence of peptide
      mobilities obtained by capillary zone electrophoresis.
AB  - Published mobility measurements obtained by capillary zone electrophoresis of
      human growth hormone peptides are described reasonably well by the classical
      theoretical relationships for electrophoretic migration. This conformity between
      theory and experiment has rendered possible a more critical assessment of a
      commonly employed empirical relationship between mobility (u), net charge (z) and
      molecular mass (M) of peptides in capillary electrophoresis. The assumed linear
      dependence between u and z/M(2/3) is shown to be an approximate description of a
      shallow curvilinear dependence convex to the abscissa. An improved procedure for
      the calculation of peptide charge (valence) is also described.

PMID- 14570332
TI  - Dispersion effects of laminar flow and spray chamber volume in capillary
      electrophoresis-inductively coupled plasma-mass spectrometry: a numerical and
      experimental approach.
AB  - Band broadening related to laminar flow and spray chamber dead volume is a
      potential problem in flow injection (FI)-inductively coupled plasma-mass
      spectrometry (ICP-MS). We studied these two dispersion effects with a sheath flow
      capillary electrophoresis (CE)-ICP-MS interface. A numerical model was used to
      simulate advection diffusion processes in the CE-capillary and dispersion in the
      spray chamber. Experimental results of FI with this CE-ICP-MS interface agree
      well with numerical modeling results. Dispersion due to laminar flow depends
      strongly on capillary diameter and analyte diffusion coefficient and to a lesser
      extent on laminar velocity and capillary length and typically amounts to one
      order of magnitude peak width increase. Three spray chambers of 5, 20 and 150 ml
      dead volume showed an increase in band broadening and peak tailing with
      increasing dead volume. The use of standard Scott-type spray chambers (>90 ml
      volume) increases peak widths by 5-10 s regardless of injection time. The use of
      a low dead volume spray chamber is recommended for experiments where resolution
      is critical. The modeling approach can be extended to the coupling of other flow
      injection techniques, like micro-LC and nano-LC with ICP-MS.

PMID- 14570333
TI  - Direct determination of phosphate esters in concentrated nitrate media by
      capillary zone electrophoresis.
AB  - The potential of capillary zone electrophoresis (CZE) for the determination of
      dibutyl phosphate (DBP) and monobutyl phosphate (MBP), two degradation products
      of the tributyl phosphate extractant used in the nuclear fuel reprocessing
      industry, was evaluated. Analysis conditions were optimised, taking particularly
      into account that many determinations had to be performed in concentrated aqueous
      nitrate or nitric acid solutions. Separations were therefore carried out using
      the counter-electroosmotic mode with cathodic detection in a pH 8.3 electrolyte
      containing a suitably selected chromophore, salicylate, to ensure the indirect UV
      detection of the analytes. Various aspects of the method, including its
      sensitivity, working range, repeatability, and rapidity, were examined.
      Quantification of both phosphate esters was achieved in less than 3 min at
      concentrations ranging from 2 x 10(-6) to 10(-3) mol l(-1) in samples containing
      no macro-component. The lower end of this range increased to 5 x 10(-6) mol l(-1)
      for MBP and 1.5 x 10(-5) mol l(-1) for DBP in samples containing 5 x 10(-2) mol
      l(-1) of sodium nitrate, thus enabling their determination in solutions
      containing nitrate or nitric acid at concentrations up to, respectively, 10,000
      and 3000 times higher than the target analyte concentration. This simple, fast
      and reliable method is routinely applicable to aqueous samples with no other
      preliminary treatment than a proper dilution; analysis was also performed in
      organic matrices after a prior extraction. The method was validated by an
      excellent correlation with the standard DBP analysis technique, gas
      chromatography (GC). In order to develop appropriate chemical treatments to
      destroy these compounds, the method was applied to the monitoring of DBP and MBP
      degradation by hydrogen peroxide in 1 mol l(-1) nitric acid solutions.

PMID- 14570334
TI  - Use of the Keele injector for sample introduction for gas chromatographic
      analysis of vinclozolin in lettuces.
AB  - We examined a Keele injector for sample introduction for gas chromatographic
      analysis of vinclozolin treated in lettuces. Samples in milligram quantity were
      introduced into a glass tube in a Keele injector at a gas chromatograph injection
      port. The glass tube was then crushed to allow the sample to carry onto a
      capillary column in a normal manner. The standard calibration curve for
      quantitative detection of vinclozolin was obtained by determining vinclozolin
      spiked in samples at variable concentrations. The calibration curve showed a
      linear response to vinclozolin ranging from 0.05 to 1.0 microg/g, giving a slope
      value of 174.8, the y-intercept value of -2.8146 and the mean r2-value of 0.9994.
      Limit of quantification for vinclozolin was 0.05 microg/g by this method,
      comparable to 0.01 microg/g by a normal injector. When samples treated previously
      with vinclozolin were determined by the Keele injector, vinclozolin was found to
      be about 30% lower as compared to a normal method, suggesting about 70% recovery
      of the spiked vinclozolin by the Keele injector. From these results, the Keele
      injector was suggested to be potential for sample introduction in gas
      chromatographic analysis of vinclozolin in lettuce samples.

PMID- 14570335
TI  - Reversed-phase porous silica rods, an alternative approach to high-performance
      liquid chromatographic separation using the sequential injection chromatography
      technique.
AB  - A commercially available porous silica rod column was used as a separation tool
      for the sequential injection analysis (SIA). A porous solid monolithic column
      showed high performance at a low pressure, allowing sequential injection analysis
      to be used for the first time for separation in HPLC fashion. In this
      contribution, we tried to demonstrate a new separation concept with SIA manifold
      for the simultaneous determination of four different compounds (methylparaben
      (MP), propylparaben (PP), triamcinolone acetonide (TCA) and internal standard
      ketoprofen (KP)) in a pharmaceutical triamcinolon cream 0.1% formulation. A
      Chromolith Flash RP-18e, 25 mm x 4.6 mm column with a 10 mm pre-column (Merck,
      Germany) and a FIAlab 3000 system (USA) with an 8-port selection valve and 10 ml
      syringe were used for sequential injection chromatographic separations in our
      study. The mobile phase used was acetonitrile-methanol-water (35:5:65, v/v/v) +
      0.05% nonylamine, pH 2.5, flow rate 0.6 ml min(-1). The analysis time was <6 min.
      A novel sequential injection chromatography (SIC) technique with UV
      spectrophotometric detection was optimised and validated.

PMID- 14570336
TI  - Antibiotic resistance: have we become the dinosaurs?

PMID- 14570337
TI  - The usefulness of personal digital assistants for health care providers today and
      in the future.

PMID- 14570338
TI  - Community-acquired pneumonia: compliance with centers for Medicare and Medicaid
      services, national guidelines, and factors associated with outcome.
AB  - BACKGROUND: This study was performed to evaluate the impact of adherence to
      national guidelines for management of community-acquired pneumonia (CAP) on
      patient outcomes. METHODS: Compliance with published national guidelines was
      assessed. Mortality rate and length of hospital stay were determined. RESULTS:
      Patients who were administered antibiotics within 4 hours of admission had a
      shorter stay. Those treated at least 8 hours after admission had the highest
      mortality. Good compliance seen with 1998 guidelines of the Infectious Diseases
      Society of America declined substantially when 2000 Infectious Diseases Society
      of America guidelines were evaluated. Pediatric compliance was difficult to
      evaluate. Documentation of vaccination screening and administration was poor.
      CONCLUSION: Antibiotic therapy should be started within 4 hours in patients with
      CAP. Using the most recent CAP guidelines as a benchmark may lower compliance
      unless providers are reeducated. National consensus guidelines for pediatric
      patients should be developed. Hospitals should evaluate documentation of vaccine
      screening and administration and should implement programs to increase
      vaccination rates if needed.

PMID- 14570339
TI  - Laboratory survey of antibiotic nonsusceptibility among Streptococcus pneumoniae
      isolates in South Carolina, 1998 versus 2000.
AB  - BACKGROUND: In 1998, the South Carolina Department of Health and Environmental
      Control surveyed clinical microbiology laboratories statewide to determine the
      prevalence of antibiotic nonsusceptibility among isolates of Streptococcus
      pneumoniae. A follow-up study was conducted in 2001. METHODS: A cross-sectional
      study was conducted to estimate the prevalence of penicillin nonsusceptibility
      (PCN-N), extended-spectrum cephalosporin nonsusceptibility (ESC-N), and
      levofloxacin nonsusceptibility (LEV-N) in South Carolina. A standardized
      questionnaire was mailed to 89 laboratories. RESULTS: The prevalence of
      penicillin intermediate resistance increased from 1998 (17.6%) to 2000 (20.9%,
      chi2 P = 0.008). Furthermore, the prevalence of PCN-N increased from 1998 (34.5%)
      to 2000 (38.4%, chi2 P = 0.01). The prevalence of ECN-N decreased from 1998
      (19.1%) to 2000 (17.7%), but the difference was not significant (chi2 P = 0.25).
      CONCLUSION: The laboratory survey was a low-cost method of estimating the change
      in prevalence of antibiotic nonsusceptibility, and it emphasizes regional
      surveillance because the prevalence of antibiotic nonsusceptibility varied
      geographically.

PMID- 14570340
TI  - Invasive group A streptococcal infections in Florida.
AB  - BACKGROUND: Several previous studies of invasive Group A streptococcal (GAS)
      disease have been hindered by small sample sizes (< or = 100 patients) and
      limited generalizability. METHODS: We conducted a population-based study of
      invasive GAS disease. The objectives of the study were to describe the clinical
      features of individuals who were hospitalized for invasive GAS disease and to
      identify risk factors for hospital mortality. The cases were 257 patients who
      were hospitalized throughout Florida during a 4-year period and reported to the
      Florida Department of Health. Logistic regression was used to calculate adjusted
      odds ratios (OR) for mortality and 95% confidence intervals (CI). RESULTS: The
      overall mortality was 18% (41 of 228). Admission into an intensive care unit was
      a strong predictor of mortality (OR, 20.41; 95% CI, 6.41-64.96). Treatment with
      clindamycin reduced mortality in patients who had necrotizing fasciitis (OR,
      0.11; 95% CI, 0.01-0.89) but not in patients who did not have necrotizing
      fasciitis (OR, 1.01; 95% CI, 0.31-3.33). CONCLUSION: Clindamycin reduces
      mortality in patients with invasive GAS disease who have necrotizing fasciitis.

PMID- 14570341
TI  - Antimicrobial resistance among isolates of respiratory tract infection pathogens
      from the southern United States: data from the PROTEKT US surveillance program
      2000/2001.
AB  - BACKGROUND: PROTEKT US (Prospective Resistant Organism Tracking and Epidemiology
      for the Ketolide Telithromycin in the United States) was established in 2000 to
      monitor antimicrobial resistance among respiratory tract pathogens across the
      United States. METHODS: During 2000 to 2001, 75 southern US centers collected
      3,867 Streptococcus pneumoniae, 1,455 Streptococccus pyogenes and 1,042
      Haemophilus influenzae. RESULTS: Overall, 46.1% of S. pneumoniae isolates were
      nonsusceptible to penicillin, 35.8% were resistant to erythromycin, and 0.5% were
      resistant to fluoroquinolones. Against S. pneumoniae the most active agents were
      telithromycin (99.7% susceptible), linezolid (99.8%) and the fluoroquinolones
      (levofloxacin 99.4%, gatifloxacin 99.5%). The prevalence of erythromycin
      resistant S. pyogenes isolates was 4.5%. Telithromycin, at concentration of < or
      = 1 mg/L, inhibited 99.9% of S. pyogenes. The prevalence of beta-lactamase
      positive H. influenzae was 26.2%. Telithromycin was active (MIC90 4 mg/L) against
      H. influenzae, irrespective of beta-lactamase production. CONCLUSION: The
      prevalence of penicillin and macrolide resistance among respiratory tract
      pathogens from the southern United States is high. Fluoroquinolone resistance is
      low. Telithromycin is highly active against respiratory tract pathogens with
      reduced susceptibility to beta-lactams, macrolides, and fluoroquinolones.

PMID- 14570342
TI  - Equal effectiveness of older traditional antibiotics and newer broad-spectrum
      antibiotics in treating patients with acute exacerbations of chronic bronchitis.
AB  - BACKGROUND: Choice of antibiotic therapy for acute exacerbations of chronic
      bronchitis (AECB) is important because of cost and concerns about development of
      resistance. METHODS: A retrospective cohort study was conducted in outpatients
      with chronic obstructive pulmonary disease and documented AECB treated with
      antibiotics. RESULTS: We compared outcomes and costs of AECB treated with first
      line antibiotics having partial coverage against organisms associated with AECB
      (eg, amoxicillin), first-line antibiotics with full coverage against organisms
      associated with AECB (eg, sulfamethoxazole-trimethoprim), and newer broad
      spectrum antibiotics (eg, azithromycin). There were no significant differences
      among the three antibiotic groups in failure rate, hospitalization rate, or time
      until subsequent AECB. Pharmacy costs were significantly less with first-line
      antibiotics (3.18 dollars +/- 0.64, 3.00 dollars +/- 0.48, and 36.70 dollars +/-
      16.29, respectively; P < 0.0001), but there was no significant difference among
      all three groups with regard to total costs. CONCLUSION: We found no difference
      in outcome between older traditional antibiotics with adequate coverage against
      organisms associated with AECB and newer broad-spectrum antibiotics.

PMID- 14570344
TI  - Clinical and educational uses of handheld computers.
AB  - Handheld computers, also known as personal digital assistants (PDAs), are
      becoming an increasingly valuable aid to physicians at the point of care. We
      review the use of handheld computers and their impact in clinical practice and
      medical education. Clinicians commonly use PDAs to access patient data and as a
      clinical reference tool. In medical education, handheld computers are most
      frequently used to track patient encounters and procedures done during medical
      school rotations and residency training. This report describes some interesting
      applications for present and future use of PDAs in inpatient care and medical
      education. Physicians and educational programs not using PDAs may wish to
      consider incorporating this technology.

PMID- 14570343
TI  - Cefazolin versus cefazolin plus metronidazole for antibiotic prophylaxis at
      cesarean section.
AB  - BACKGROUND: Although prophylactic antibiotic medications have been shown to
      reduce the incidence of postoperative infectious morbidity after cesarean
      delivery, the most effective regimens have not been established. The purpose of
      this investigation was to compare the efficacy and costs of prophylaxis with
      cefazolin alone with cefazolin plus metronidazole. METHODS: Women undergoing
      cesarean delivery were randomized to prophylaxis with 2 g cefazolin (n = 81) or 1
      g cefazolin plus 500 mg metronidazole (n = 79). Postoperative infectious
      morbidity and the duration of hospitalization in the two groups were compared.
      RESULTS: Thirty-seven (23%) of 160 patients developed endomyometritis. There was
      a significant reduction in the number of postoperative infections (14 versus 32%)
      and hospital days (3.12 versus 4.46) with cefazolin and metronidazole prophylaxis
      (P = 0.0064 versus P = 0.014) compared with cefazolin alone. The estimated
      antibiotic prophylaxis cost per person was less with cefazolin and metronidazole
      than with cefazolin alone (9.12 dollars versus 26.73 dollars). CONCLUSION:
      Antibiotic prophylaxis with metronidazole and cefazolin results in fewer
      postoperative infections, decreased duration of hospitalization, and lower
      medication cost than cefazolin alone.

PMID- 14570345
TI  - Outcomes of a program in business education for physicians and other health care
      professionals.
AB  - BACKGROUND: We sought to determine the expectations that graduates of one
      business of medicine program had upon enrollment and to ascertain fulfillment of
      those expectations after completion, as well as the extent to which participating
      in the program improved business skills and led to advancement in office practice
      or career development. METHODS: A postal mail survey was conducted of graduates
      of The Johns Hopkins University's Business of Medicine Program, a year-long, four
      course certificate program to educate midcareer academic and nonacademic
      physicians and other health care professionals about fundamental business
      practices and their application to health care. RESULTS: Surveys were sent to 285
      graduates, and responses were received from 136 (48%) of them. Most respondents
      expected the program to expand their management skills, to enhance their
      knowledge of marketplace trends, and to advance their careers. These results were
      not correlated with respondents' age, sex, or profession (ie, physician, non
      physician). More than 87% of respondents agreed that their overall expectations
      had been fulfilled by the time they completed the survey. Participants noted,
      however, that several expectations were unfulfilled upon replying to the survey.
      CONCLUSION: Programs designed to educate physicians and other health care
      professionals--in private practice, academia, or industry--about the business
      aspects of medicine can be effective but need to be designed carefully to
      integrate business theory and application to the medical setting.

PMID- 14570346
TI  - Prevention and management of antibacterial resistance for primary care patients
      with respiratory tract infections.
AB  - This review examines the problem of increasing antibacterial resistance among the
      pathogens commonly associated with community-acquired respiratory tract
      infections, particularly Streptococcus pneumoniae, Haemophilus influenzae, and
      Moraxella catarrhalis. The increases in morbidity, mortality, and treatment cost
      associated with increased resistance to available antibiotics are challenging
      prescribers to find more effective therapeutic strategies. A MEDLINE search of
      the literature from 1966 to the present was performed to seek data relevant to
      the issue of resistance, especially the negative effects on patient outcomes and
      costs of therapy. Several observations and conclusions emerged. Data are lacking
      on local resistance patterns, broad-spectrum agents are overprescribed when
      narrower-spectrum choices would be more appropriate, a need exists for
      educational programs to encourage restricting drug use and changing prescribing
      habits, and there is a need for new antibiotic choices. The best antibiotic
      options are agents with a tailored spectrum of activity that are targeted at
      particular respiratory tract pathogens and have low potential to select for
      resistant organisms.

PMID- 14570347
TI  - Neurocysticercosis: a neurosurgical perspective.

PMID- 14570348
TI  - Antihistamine-induced rhabdomyolysis.
AB  - Antihistamines, which are readily available over the counter in sleeping aids,
      are commonly found in intentional overdoses. We report three new cases of severe
      rhabdomyolysis related to ingestion of these agents. This is a rarely reported
      but potentially overlooked complication among patients who present to the
      emergency center after intentional overdoses. We also describe the potential
      mechanism of muscle injury in antihistamine overdoses and comment on the
      potential for cross-reactivity of antihistamines with the urine screen for
      phencyclidine.

PMID- 14570349
TI  - Primary human immunodeficiency virus type 1 infection in a patient with acute
      rhabdomyolysis.
AB  - Primary human immunodeficiency virus type 1 (HIV-1) infection (acute retroviral
      syndrome) has been well characterized as a mononucleosis-like illness.
      Manifestations of HIV-1 infection such as pharyngitis, fever, morbilliform rash,
      myalgias, arthralgias, nausea, headache, emesis, and lymphadenopathy have been
      reported. Acute rhabdomyolysis has been reported as part of the acute retroviral
      syndrome on 11 different occasions. We report the case of a primary HIV-1
      infection with acute rhabdomyolysis and review critically the other case reports.

PMID- 14570350
TI  - Selective serotonin reuptake inhibitor-induced rhabdomyolysis associated with
      irinotecan.
AB  - A 74-year-old man was admitted with rhabdomyolysis after undergoing initial
      treatment for gastrointestinal cancer with irinotecan. The syndrome partially
      resolved after the discontinuation of all of his usual medications, including his
      chronic selective serotonin reuptake inhibitor (SSRI). The rhabdomyolysis was
      exacerbated upon reinitiation of the SSRI and disappeared when the SSRI was
      discontinued. The combination of irinotecan and SSRI resulted in potentially
      lethal rhabdomyolysis.

PMID- 14570351
TI  - Rhabdomyolysis associated with simvastatin-nefazodone therapy.
AB  - Simvastatin is a hydroxymethyl glutaryl coenzyme A reductase inhibitor commonly
      used to treat patients with hyperlipidemia. It is a safe and effective medication
      in most patients when used appropriately. A serious side effect known as
      rhabdomyolysis may rarely occur in patients who take simvastatin, especially at
      higher doses and with agents that interact and increase the level of simvastatin
      in the blood. We describe the case of a patient with rhabdomyolysis that occurred
      after the patient's simvastatin was titrated to 80 mg at approximately the same
      time that his antidepressant medication was switched to nefazodone. We found only
      two other similar cases in the literature, both of which were presented as
      letters to the editor in two different journals. We present this case to add to
      the literature and to assist practitioners by raising their awareness of this
      interaction so that it can be monitored.

PMID- 14570352
TI  - Near-fatal air embolism: fibrin sheath as the portal of air entry.
AB  - Complications of central venous catheters occur in less than 1% of all
      insertions. Of these, pulmonary air embolism is a rare though often fatal
      complication. Possible mechanisms include opening of the line to the atmosphere
      during use and poor technique during insertion or removal. There has also been
      speculation that the presence of a fibrin sheath after removal might be a
      mechanism for air entry. We present a case of a near-fatal pulmonary air embolus
      with documentation of air in the pulmonary outflow trunk and a residual air
      filled fibrin tract seen on computed tomography.

PMID- 14570353
TI  - An alternative technique for nasotracheal intubation.
AB  - Surgical procedures on structures of the oral cavity or the mandible may require
      nasotracheal intubation to allow for surgical access. Even with appropriate
      technique, trauma to the nasopharynx may occur, resulting in bleeding. The
      authors describe an alternative technique involving the placement of the flanged
      end of a red rubber catheter over the distal tip of the endotracheal tube (ETT)
      to decrease the potential for trauma as the ETT passes through the nasopharynx.

PMID- 14570354
TI  - Gangrenous appendicitis in a strangulated obturator hernia.
AB  - Only two cases of appendicitis in strangulated obturator hernia have been
      previously reported. In the present case, an 83-year-old woman had fatal
      anaerobic myonecrosis of the thigh that resulted from gangrenous appendicitis in
      the right obturator foramen. Early diagnosis, prompt surgical intervention, and
      perioperative resuscitation are critical for survival in a case of appendicitis
      in a strangulated obturator hernia with thigh sepsis, especially when it occurs
      in an elderly, emaciated female patient.

PMID- 14570355
TI  - James H. Quillen VA celebrates its centennial anniversary: 1903-2003.

PMID- 14570356
TI  - Characterizing the performance and outcomes of obesity surgery in California.
AB  - Between 1991 and 2000, the prevalence of obesity increased 65 per cent. As a
      result, increasing research is being directed at gastric bypass (GB) surgery, an
      operation that appears to achieve long-term weight reduction. Despite the rapid
      proliferation of this surgery, the quality of care at a population level is
      largely unknown. This study examines longitudinal trends in quality and
      identifies significant predictors of adverse outcomes. Using the California
      inpatient discharge database, all GB operations from 1996 to 2000 were
      identified. Demographic, comorbidity, complication, and volume data were
      obtained. Complications were defined as life-threatening cardiac, respiratory, or
      medical (renal failure or shock) events. Comorbidity was graded on a modified
      Charlson score. Annual hospital volume was categorized into four groups: < 50, 50
      99, 100-199, and 200+ cases. Based on these data, we calculated longitudinal
      trends in complication rate and performed logistic regression to identify
      predictors of complications. A total of 16,232 patients were included. The
      average age was 41 years; 84 per cent were female, and 83.5 per cent were white.
      The complication rate was 10.4 per cent. Between 1996 and 2000, rates of cardiac
      and respiratory complications decreased while rates of medical complications
      remained unchanged. Complications were more likely in men [odd ratio (OR) = 1.69
      compared to women] and in patients with comorbidities (OR = 1.60 for each
      additional comorbid disease). Furthermore, when examining the effect of volume,
      patients at very low (< 50) and low (50-99) volume hospitals were much more
      likely to have complications (OR = 2.72 and 2.70, respectively) compared to
      patients at high-volume hospitals (200+), even after controlling for differences
      in case-mix. The quality of care for obesity surgery has improved between 1996
      and 2000. Despite operating on patients with more comorbidity, rates of cardiac
      and respiratory complications have decreased. Furthermore, this study identifies
      three independent predictors of complications: gender, comorbidity, and hospital
      volume. These findings are important initial steps toward improving quality in
      obesity surgery.

PMID- 14570357
TI  - Appendiceal abscess: immediate operation or percutaneous drainage?
AB  - Conflicting evidence exists regarding the optimal treatment for abscess
      complicating acute appendicitis. The objective of this study is to compare
      immediate appendectomy (IMM APP) versus expectant management (EXP MAN) including
      percutaneous drainage with or without interval appendectomy to treat
      periappendiceal abscess. One hundred four patients with acute appendicitis
      complicated by periappendiceal abscess were identified. We compared 36 patients
      who underwent IMM APP with 68 patients who underwent EXP MAN. Outcome measures
      included morbidity and length of hospital stay. The groups were similar with
      regard to age (30.6 +/- 12.3 vs. 34.8 +/- 13.5 years), gender (61% vs. 62%
      males), admission WBC count (17.5 +/- 5.1 x 10(3) vs. 17.0 +/- 4.8 x 10(3)
      cells/dL), and admission temperature (37.9 +/- 1.2 vs. 37.8 +/- 0.9 degrees F).
      IMM APP patients had a higher rate of complications than EXP MAN patients at
      initial hospitalization (58% vs. 15%, P < 0.001) and for all hospitalizations
      (67% vs. 24%, P < 0.001). The IMM APP group also had a longer initial (14.8 +/-
      16.1 vs. 9.0 +/- 4.8 days, P = 0.01) and overall hospital stay (15.3 +/- 16.2 vs.
      10.7 +/- 5.4 days, P = 0.04). We conclude that percutaneous drainage and interval
      appendectomy is preferable to immediate appendectomy for treatment of appendiceal
      abscess because it leads to a lower complication rate and a shorter hospital
      stay.

PMID- 14570358
TI  - Laparoscopic Nissen fundoplication improves quality of life in patients with
      atypical symptoms of gastroesophageal reflux.
AB  - Laparoscopic Nissen fundoplication has been shown to improve overall quality of
      life (QOL) in patients with gastroesophageal reflux, but most studies have not
      addressed patients with atypical symptoms. We investigated the effect of
      laparoscopic Nissen fundoplication on QOL using the Gastrointestinal Quality of
      Life Index (GIQLI) survey modified to address both typical (heartburn,
      regurgitation, dysphagia) and atypical (hoarse voice, chronic cough, adult-onset
      asthma, vocal cord polyps) symptoms. One-hundred forty-eight patients underwent
      laparoscopic Nissen fundoplication for gastroesophageal reflux disease (GERD) at
      UCLA Medical Center from January 1, 1995 to May 1, 2002. Surveys evaluating pre-
      and postoperative QOL were administered after surgery: 55 per cent of patients
      responded (82/148). Forty-eight per cent of all patients (72/148) had atypical
      symptoms. Perioperative morbidity and mortality were 8.8 per cent and 0.7 per
      cent, respectively. Mean length of postoperative stay was 2.96 +/- 1.5 days. Mean
      follow-up for the entire cohort was 18.5 months. Postoperative dysphagia not
      present before surgery occurred in 4.7 per cent of patients. Eighty per cent of
      patients were medication-free following surgery. QOL scores for all participants
      increased significantly from 52.5 +/- 15.3 preoperatively to 72.0 +/- 14.9
      postoperatively (P < 0.0001). Patients with atypical symptoms or typical symptoms
      alone showed significant mean QOL score increases from 48.3 +/- 17.6
      preoperatively to 71 +/- 15.7 postoperatively (P < 0.0001) and from 55.7 +/- 12.6
      to 72.8 +/- 14.4 (P < 0.0001), respectively. Laparoscopic Nissen fundoplication
      can effectively improve overall QOL for patients with GERD. Patients with
      atypical GERD symptoms can experience increases in QOL similar to those with only
      typical gastrointestinal symptoms.

PMID- 14570359
TI  - Disability and chronic pain after open mesh and laparoscopic inguinal hernia
      repair.
AB  - Proponents of laparoscopic inguinal hernia repair maintain that the associated
      costs and risks are offset by faster recovery and less postoperative pain. It was
      our hypothesis that the incidence of chronic pain in both groups of our patients
      was not as high as reported in the literature. Patients for the study were
      identified from a community hospital medical record database. A total of 229
      patients were available and agreed to participate in the study. Data collected
      included the patient's current pain level at the hernia site, pain medication
      currently used, narcotics currently used, return to normal work, and return to
      normal activity. Overall, 19.7 per cent of patients complained of mild pain, but
      only 2.2 per cent classified this as moderate or severe. Mild pain was noted more
      often in the open repair patients compared with the laparoscopic group. However,
      there was no difference in the frequency of moderate or severe pain. The time to
      return to work was longer in the open repair group than the laparoscopic repair
      group, but there were large ranges in both groups. The inability to return to
      full preoperative activity was infrequent and equivalent in both open and
      laparoscopic hernia repair groups. In our study of 229 patients undergoing
      elective open or laparoscopic inguinal hernia repair at a community hospital, we
      have found a low incidence of moderate or severe chronic pain. In addition, we
      found that this procedure did not interfere with return to work at 6 months or
      return to daily activities in either the laparoscopic or open repair group.

PMID- 14570360
TI  - Computed tomography angiography validates duplex sonographic evaluation of
      carotid artery stenosis.
AB  - Controversy regarding the optimal preoperative evaluation for patients with
      carotid arterial stenosis remains controversial. We hypothesized that carotid
      artery area reduction measured by computed tomography angiography (CTA) would
      closely correlate with duplex scanning stenosis. This study was undertaken to
      evaluate the correlation between duplex, CTA, and conventional arteriography in
      patients undergoing consideration for carotid endarterectomy. Patients undergoing
      evaluation for carotid artery stenosis who received at least 2 of the diagnostic
      tests were included in this study (n = 108); 30 patients underwent all 3 imaging
      modalities. Linear regression analysis was performed to determine correlation
      coefficients between the 3 different study modalities. Correlation and P values
      were as follows: CTA area versus CTA diameter, r = 0.82, P < 0.001; CTA area
      versus duplex stenosis, r = 0.71, P < 0.001; duplex stenosis versus angio
      diameter, r = 0.68; P = 0.005; CTA diameter versus angio diameter, r = 0.61, P =
      005. CTA was able to identify plaque characteristics more readily than duplex or
      arteriography. CTA was also able to differentiate critical stenosis from
      occlusion and to settle discrepancies obtained from duplex scanning. CTA is an
      acceptable alternative method to validate duplex scanning evaluation of carotid
      artery stenosis. It can accurately measure lumen stenosis, visualize plaque
      morphology, and is associated with fewer complications than conventional
      angiography.

PMID- 14570361
TI  - Vascular injuries to the extremities in a suburban trauma center.
AB  - The purpose of this study was to examine the experience with extremity vascular
      injuries of a level II suburban trauma center. A retrospective chart review was
      undertaken to include all patients admitted in a 6-year period with vascular
      injuries to the extremities. The vessels injured were identified along with the
      mechanism of injury. The method of repair was recorded. All associated neurologic
      injuries were investigated. Follow-up records, when available, were reviewed.
      Between January 1, 1996, and November 30, 2002, 48 patients were admitted with 56
      vascular injuries to the extremities. Blunt trauma was the mechanism in 24
      patients while penetrating trauma was the mechanism in the other 24 patients. The
      limb salvage rate was 95 per cent. Of the 28 injuries to upper extremity vessels,
      24 were associated with neurologic injuries. In contrast, only 3 neurologic
      injuries were found in patients with lower extremity vascular injuries. In
      contrast to most urban centers, the distribution of vascular injuries to the
      extremities in a suburban setting was equally divided between blunt and
      penetrating injuries. The majority of functional impairment was related to
      neurologic injury rather than tissue ischemia from vascular injury.

PMID- 14570362
TI  - Does reoperation predispose to postoperative wound infection in women undergoing
      operation for breast cancer?
AB  - Reoperations for breast cancer predispose to a higher risk of postoperative wound
      infections than primary procedures. We accomplished a retrospective chart review
      of 320 women who underwent multiple breast cancer procedures between 10/97 and
      8/02. The mean number of procedures was 2.4 (range, 2-5). The overall incidence
      of wound infection was 6.1 per cent. Wound infections developed, on average, 12
      days after surgery (range, 2-30). There was a statistically significant
      difference in the incidence of wound infection comparing the initial procedure
      versus the subsequent operation (1.6% vs. 9.4%, P < 0.001). This was also seen
      with reoperation after an operative biopsy compared to operation after a core
      biopsy (11.1% vs. 9.7%, P < 0.01). The incidence was increased to 22.0 per cent
      when the initial operation involved lymph node dissection (sentinel lymph node
      biopsy or complete axillary lymph node dissection). Wire localization did not
      increase the incidence of postoperative wound infections, and prophylactic
      antibiotics were associated with a decreased incidence of wound infection in the
      reoperative setting. The incidence of wound infection is increased with
      reoperation after operative biopsy compared to operation after core biopsy and is
      further increased when the initial biopsy involved lymph node dissection.

PMID- 14570363
TI  - The incidence of thromboembolism in the surgical intensive care unit.
AB  - The clinical diagnosis of deep venous thrombosis (DVT) is unreliable. Studies
      have been performed examining the utility of frequent duplex scans. However,
      these studies included patients outside of the intensive care unit. The incidence
      of venous thromboembolism and the effect of a less intense surveillance protocol
      was prospectively examined at a level-1 urban trauma center for a 6 month period.
      During the study period there were 726 admission to the surgical intensive care
      unit. Sequential compression devices (SCDs) were used for DVT prophylaxis in 93
      per cent of the admissions. A total of 114 duplex scans were ordered: 42 per cent
      for surveillance and the rest for evaluation of a clinical indication. Twelve
      DVTs were discovered (11% overall DVT rate). No patient on subcutaneous heparin
      or low-molecular-weight heparin developed a DVT or pulmonary embolism (PE). Four
      patients suffered a PE; however, none were found to have a lower extremity DVT on
      duplex ultrasound and all received SCD prophylaxis. Overall, proper use of DVT
      prophylaxis for intensive care unit days 1-14 was 77 per cent. The incidence of
      venous thromboembolism in a group of patients at overall high risk was low. A
      program of DVT surveillance with duplex ultrasound was not cost-effective.

PMID- 14570364
TI  - Stapled hemorrhoidectomy: a review of our early experience.
AB  - Treatment of hemorrhoids may safely be accomplished by using a circular stapler
      instead of the conventional open procedure for large symptomatic hemorrhoids. Our
      purpose was to assess the safety and early post-op results of this new surgical
      technique as it was introduced into clinical practice. Medical records from 62
      patients treated by circumferential mucosectomy/stapled hemorrhoidectomy were
      obtained from 6 surgeons. Preoperative factors assessed included demographics,
      comorbidities, prior anorectal surgery, hemorrhoid grade, and the indications for
      surgery. Operative factors examined included operating time, use of perioperative
      antibiotics, and oversewing of the suture line. Postoperative factors included
      complications and date of last follow-up. Sixty-two patients underwent this
      operation, and complications were reported in six patients (10%). There was one
      death unrelated to the hemorrhoid surgery. Postoperative pain, defined as
      requiring pain control with intravenous medication, hospital admission, or an
      emergency department visit, occurred in two patients. Two patients reported
      postoperative bleeding. One patient experienced bleeding the first evening, and
      the second patient had bleeding 1 week postoperatively. The first patient was
      admitted overnight and required no blood transfusion or further intervention. The
      second patient was subsequently found to have a bleeding diverticulum. One
      patient experienced urinary retention that resolved with conservative management.
      Postoperative follow-up was available for over 90 per cent of the patients at a
      median of 4 weeks postoperatively. No additional complications were discovered at
      follow-up. This data suggests that stapled hemorrhoidectomy is a safe and
      effective approach to hemorrhoidal disease. Our findings indicate an acceptable
      complication rate among a group of surgeons beginning to integrate this modality
      into clinical practice.

PMID- 14570365
TI  - Rates of colon and rectal cancers are increasing in young adults.
AB  - Incidence rates for colorectal cancer are decreasing in the United States,
      possibly due to preventative cancer screening. Because these programs target
      older patients, their beneficial effects may not apply to young patients. The
      purpose of this study was to compare incidence rates and tumor characteristics of
      colon and rectal cancers for young versus older patients using a population-based
      cancer registry. Colon and rectal cancer patients reported in the Surveillance,
      Epidemiology, and End Results registry (1973-1999) were separately analyzed.
      Incidence rates over time, stage, and grade were compared for two age groups:
      young patients (20-40 years, n = 5383) and older patients (60+ years, n =
      256,401). For older patients, colon cancer incidence remained stable while rectal
      cancer incidence decreased 11 per cent to 72.1/100,000 persons (P < 0.05). For
      the young, colon cancer incidence increased 17 per cent to 2.1 (P < 0.05), and
      rectal incidence rose 75 per cent to 1.4 (P < 0.05). Young patients had less
      localized tumors than older patients: colon (25.8% vs. 35.3%, P < 0.001); rectal
      (38.4% vs. 41.7%, P = 0.005). Young patients also had more poorly differentiated
      tumors: colon (22.2% vs. 14.7%, P < 0.001); rectal (16.4% vs. 12.3%, P < 0.001).
      Incidence rates for colon and rectal cancers in young patients are rising, and
      they have more advanced disease. Although the overall prevalence is low in this
      population, the increasing incidence suggests health-care providers should have
      heightened awareness when caring for this population.

PMID- 14570366
TI  - Interval jejunoileal bypass reduces the morbidity and mortality of Roux-en-Y
      gastric bypass in the super-obese.
AB  - Among Roux-en-Y gastric bypass (RYGB) patients, large male patients carry the
      greatest risk for severe, life-threatening complications. The higher complication
      rate is partly related to large amounts of intra-abdominal fat that increases the
      technical difficulty of the RYGB. In order to minimize the risk for
      complications, we established a staged approach for weight loss surgery for high
      risk, super-obese patients. Patients with intra-abdominal fat at exploration
      which precluded the performance of RYGB underwent jejunoileal bypass (JIB).
      Following an initial period of weight loss (6-24 months), they were converted to
      a RYGB during a second operation. Twenty-four patients underwent initial JIB that
      was associated with a major complication rate of 8.3 per cent (2/24) and no
      mortality. Eight patients lost 53.4 +/- 6.3 kg prior to their conversion to RYGB
      (mean, 14.1 months). There was one major complication (12%) and no deaths (0%).
      Following RYGB, an additional period of weight loss resulted in overall excess
      weight loss (EWL) totaling 62 per cent. A two-step procedure is a safe and
      effective approach for minimizing complications for high-risk patients undergoing
      RYGB. The initial JIB was associated with low morbidity and no mortality, and the
      follow-up RYGB procedure was a technically simple operation that could be
      performed with few complications.

PMID- 14570367
TI  - Prevalence of metastases in hepatocellular carcinoma: risk factors and impact on
      survival.
AB  - The purpose of this study was to determine the prevalence and risk factors of
      metastases in hepatocellular carcinoma (HCC) patients and analyze the effects of
      different locations of metastases on survival. Retrospective analysis was
      performed on 347 HCC patients who received a metastatic workup including bone
      scan and computed tomography scans of chest, abdomen, and pelvis. Clinical and
      tumor characteristics were evaluated as risk factors for metastasis by univariate
      and multivariate methods. Survival was analyzed by Kaplan-Meier and Cox
      regression methods. One hundred forty-five patients had metastases: 72 had
      thoracic, 57 had abdominal, and 34 had bone metastases. Significant differences
      were noted with weight loss, hepatitis C, tumor grade, tumor multifocality, size,
      and alkaline phosphatase levels between the metastases group and the
      nonmetastases group by univariate analysis. Poor differentiation, multilobar
      spread, and size (> or = 5 cm) were strongest predictors of metastatic disease by
      logistic regression. Patients with thoracic metastases had significantly poorer
      survival. HCC metastasis is prevalent on initial presentation. Evaluation for
      liver transplantation or curative resection requires a full metastatic workup.
      Poor differentiation, larger tumors, and those with multilobar spread have
      increased risk for metastasis. Patients with thoracic spread have poor prognosis
      as compared to other locations of metastasis.

PMID- 14570368
TI  - Lymphatic tumor burden negatively impacts the ability to detect the sentinel
      lymph node in breast cancer.
AB  - Sentinel lymph node (SLN) biopsy is the preferred method of nodal breast cancer
      staging. Techniques of SLN biopsy rely on transport of interstitial molecules
      through mammary lymphatics. Lymphatic flow may be disrupted by tumor emboli.
      Increased lymphatic tumor burden may be responsible for failure to identify the
      sentinel lymph node in patients with breast cancer. A prospective database of 110
      patients who had SLN biopsy between January 2001 and December 2002 was analyzed.
      The number of metastatic axillary lymph nodes was used as a measure of lymphatic
      tumor burden. SLN was found in 94 per cent of cases. It was not found in seven
      patients; five of them had extensive axillary metastases (71%) compared to 23 per
      cent when SLN was found (P = 0.001). The average number of metastatic lymph nodes
      was larger when SLN was not found compared to when SLN was found (12.8 vs. 3.9,
      respectively, P = 0.002). Increasing numbers of metastatic nodes correlated with
      decreasing success in SLN biopsy (P = 0.075). The incidence of axillary
      metastases is higher in patients in whom the sentinel node is not found. High
      lymphatic tumor burden may have a causative role in SLN biopsy technical failure.
      Axillary dissection should be performed if SLN is not found, regardless of the
      tumor size or histology.

PMID- 14570369
TI  - Intubation after cervical spinal cord injury: to be done selectively or
      routinely?
AB  - Patients with cervical spinal cord injuries (CSCIs) often develop acute
      respiratory failure and require intubation. It is unknown if intubation should be
      offered preemptively in all CSCI patients or selectively based on signs of acute
      respiratory failure. The purpose of this study was to evaluate the role of
      routine early intubation in CSCI patients. The medical records of 68 patients
      with CSCI were reviewed. Univariate and multivariate analyses were used to
      identify independent risk factors for the need of intubation. Statistical
      significance was considered at P < 0.05. Fifty patients (74%) required intubation
      and 27 (40%) developed pneumonia. Of patients with CSCI above C5, 87.5 per cent
      required intubation compared with 61 per cent of patients with CSCI at C5-C8 (P =
      0.026). Similarly, of patients with complete quadriplegia, 90 per cent required
      intubation compared to 48.5 per cent of patients with incomplete quadriplegia or
      paraplegia (P < 0.001). Of 31 patients not presenting with overt signs of acute
      respiratory failure on admission, 13 (42%) decompensated later and were
      eventually intubated up to 53 hours after admission. Six of these 13 patients had
      emergent intubation due to acute desaturation and developed pulmonary
      complications associated with emergent intubation. There were 3 independent risk
      factors for the need of intubation: Injury Severity Score > 16, CSCI higher than
      C5, and complete quadriplegia. The combination of the 2 latter risk factors
      resulted in intubation in 21 of 22 patients (95%). The majority of patients with
      CSCI require intubation. In patients with CSCI above C5 and complete
      quadriplegia, intubation should be offered routinely and early because delays may
      cause preventable morbidity.

PMID- 14570370
TI  - Patterns of injury and outcomes associated with motocross accidents.
AB  - Motocross has become a popular recreation activity in Southern California,
      particularly in the Inland Empire area. In order to evaluate the patterns of
      injury and outcomes associated with motocross accidents, the Trauma Registry data
      and charts of all patients with motocross-related injuries from January 2000 to
      December 2001 were reviewed. Of the 270 patients studied, 265 were males and 5
      were females, with a mean age of 26 years (range, 5-61). The mean Injury Severity
      Score was 6.8 (range, 1-38). Injuries involved extremity trauma in 52 per cent of
      patients closed head injuries in 33 per cent, blunt chest trauma in 23 per cent,
      abdominal trauma in 15 per cent, spinal trauma in 14 per cent, and pelvic trauma
      in 8 per cent. Surgery was required in 96 patients (36%), most commonly for
      treatment of orthopedic injuries. After initial evaluation, 179 patients were
      admitted (66%), 60 were discharged home (22%), 29 were transferred for higher
      level of care (11%), and two expired (1%). The mean hospital length of stay was
      2.3 days (range, 1-9). Motocross accidents are most commonly associated with
      extremity injuries and closed head trauma. Although the overall mortality is low,
      the morbidity is high, with a large proportion of patients requiring surgery.

PMID- 14570371
TI  - Factitious oxygen desaturation after isosulfan blue injection.
AB  - Profound pulse oximetery desaturations are observed following isosulfan blue dye
      injection during breast sentinel node biopsy. The objective of this study was to
      examine the effect isosulfan dye has on oxygenation status and the reliability of
      pulse oximetery in evaluating this parameter. After study design, institutional
      review board approval was obtained. A prospective 5-month study was performed
      between January and April 2002. Twenty-one women with invasive breast cancer were
      monitored during breast sentinel node biopsies. Twenty-two operative cases were
      analyzed by pulse oximetry and arterial catheterization to record oxygen
      saturation. Time intervals of analysis were 0, 5, 10, 20, 30, and 40 minutes
      following injection of isosulfan blue dye. Simultaneous pulse oximetry and
      arterial blood gas analysis allowed comparison of indirect oximetry oxygen
      saturation (SpO2) to actual arterial oxygen saturation (SaO2). SpO2 values were
      decreased from baseline values at 10, 20, and 30 minutes without decrease in SaO2
      saturation (P < 0.001). The mean oximetry SpO2 desaturation was 5.6 per cent,
      with a range to 9 per cent. After injection with isosulfan blue dye, a
      significant SpO2 desaturation occurs. Clinicians must be aware of the factitious
      effect isosulfan blue dye has on SpO2 monitoring, to assess accurately the
      oxygenation status of the anesthetized patient.

PMID- 14570372
TI  - Appendicitis, 2002: relationship between payors and outcome.
AB  - As the status of health-care insurance changes in the United States, studies have
      indicated that uninsured patients are less likely to receive timely and quality
      health care. Previous studies of appendicitis have shown that insurance status
      may effect the stage of presentation and outcome. However, these studies were
      based on databases lacking information regarding stage of presentation,
      timeliness of diagnosis and treatment, and character of hospitalization (length
      of stay, duration of antibiotic therapy, hospital costs). We accomplished a case
      control study, retrospective analysis of 975 patients treated for acute
      appendicitis between January 1996 and December 1999. Times to operation, number
      of preoperative outpatient visits, number of studies, severity of presentation,
      length of antibiotics and hospital stay, and hospital costs were analyzed
      [analysis of variance (ANOVA) techniques, P < 0.05 significant]. We sought
      answers to the following: (1) Did insurance status affect the timeliness of
      diagnosis and treatment? (2) Did insurance status affect the stage of
      presentation? (3) Did insurance status affect hospitalization, as measured by
      length of stay, duration of antibiotic therapy, and hospital costs? (4) Did age
      affect outcome independent of insurance status? There were no correlations
      between insurance status and timeliness of diagnosis or severity of presentation.
      Length of stay and hospital costs were also not different between insurance
      categories. Pediatric patients (< 12 years old) and the elderly (> 65 years old)
      presented with more advanced appendicitis, independent of insurance category. In
      contrast to previously published data, the treatment of acute appendicitis is not
      affected by insurance coverage in the sample community. Age and timeliness of
      presentation were the only factors correlating to outcomes.

PMID- 14570374
TI  - Analysis of causes and prevention of early readmission to surgical intensive
      care.
AB  - The purpose of this study was to analyze causes of early readmission to the
      surgical intensive care unit (SICU), to determine whether readmission can be
      predicted or prevented, and to compare outcomes of patients readmitted to the
      SICU with patients not requiring readmission. All patients admitted to the Cedars
      Sinai SICU from January 1, 1996, to December 31, 2001, were included. Clinical
      data was prospectively collected in an on-line computer system. The charts of all
      early readmission patients were retrospectively reviewed. SICU and hospital
      outcomes were abstracted from a computerized data warehouse. During the study
      period, 10,840 patients were admitted to the SICU including 97 (0.89%) early
      readmissions. SICU admission APACHE II and SAPS I scores, SICU and hospital
      length of stay, and mortality were significantly higher in readmitted patients
      compared to patients not requiring readmission. The majority of early SICU
      readmissions were due to respiratory and neurologic deterioration. Upon review,
      62 per cent of all readmissions met appropriate SICU discharge criteria and were
      not predictable while only 5 per cent of SICU discharge were felt to have been
      premature. Patient outcomes are adversely affected by early readmission to the
      SICU. Careful neurologic assessment, meticulous attention to respiratory care
      transfer orders, and prompt respiratory therapy on floor care may significantly
      decrease the need for early readmission to the SICU.

PMID- 14570373
TI  - Liberalization of donor criteria in lung transplantation.
AB  - Donor shortage remains a major obstacle to widespread application of lung
      transplantation. In region 5, including California, Nevada, New Mexico, Utah, and
      Arizona, the United Network of Organ Sharing (UNOS) database median waiting time
      for lung transplant candidates in 2000-2001 exceeded 17 months. The purpose of
      this study was to determine the impact of liberalization of donor criteria on
      median waiting time and short-term outcome of lung transplantation. From
      September 1999 to October 2002, 42 patients underwent lung transplantation from
      nonstandard donors. The donors were classified as nonstandard due to (1)
      infiltrate on chest radiograph (n = 33), (2) PaO2 < 300 on FiO2 1.0 and PEEP 5 (n
      = 3), (3) PaO2 < 100 on FiO2 0.4 and PEEP 5 (n = 3), (4) purulent sputum on
      bronchoscopy (n = 22), and (5) smoking history greater than 50 pack-years (n =
      1). Perioperative characteristics and short-term outcome of this group was
      analyzed. The median waiting time for this cohort was 114 days (range, 10-1267),
      as compared with the national UNOS database median waiting time of 24 months
      between 1996 and 2001. The incidence of ischemia reperfusion injury was 2.3 per
      cent. None of the recipients developed pneumonia. The median ventilator support
      time was 2 days (range, 1-95). The median ICU stay and hospital stay were 4 days
      (range, 2-103) and 14 days (range, 5-194), respectively. The 3-month survival was
      97.6 per cent. Selective liberalization of donor lung criteria can decrease the
      waiting time and is associated with favorable short-term outcome. Utilization of
      nonstandard lungs can expand the donor pool.

PMID- 14570375
TI  - Differential expression of thymidylate synthase in colorectal tumors and matched
      lymph nodes: impact on adjuvant treatment.
AB  - Although the expression of thymidylate synthase (TS) in metastatic colorectal
      cancer (CRC) may be a better predictor of response to 5-fluorouracil chemotherapy
      than TS expression in primary CRC, this enzyme has not been well studied in tumor
      draining regional lymph nodes. We retrospectively examined TS expression in 12
      primary CRC lesions (pT3) and matched sentinel lymph nodes. Of the 8 primary
      tumors that were TS-positive, 50 per cent (4/8) had tumor-positive lymph nodes
      and 50 per cent (4/8) had tumor-negative nodes. Of the 4 primary tumors that were
      TS-negative, 75 per cent (3/4) had tumor-positive nodes and 25 per cent (1/4) had
      tumor-negative nodes [kappa = -0.1386, 95 per cent confidence interval: (-0.4820,
      0.2048), P = 0.4284]. Of the 8 TS-positive primaries, 25 per cent (2/8) had TS
      positive nodes and 75 per cent (6/8) had TS-negative nodes. Of the 4 TS-negative
      primaries, 50 per cent (2/4) had TS-positive nodes and 50 per cent (2/4) had TS
      negative nodes [kappa = -0.0131, 95 per cent confidence interval: (-0.2958,
      0.2696), P = 0.9274]. Two of the three TS-negative primaries that had
      metastasized to regional lymph nodes were associated with TS-positive lymph
      nodes. Our findings indicate that expression of TS by a primary CRC does not
      correlate with nodal metastases or nodal TS expression. Nodal expression of TS
      may be important in predicting response to 5-fluorouracil when a primary CRC is
      TS-negative.

PMID- 14570376
TI  - C. elegans: the cell lineage and beyond.

PMID- 14570377
TI  - Cyclosporin A-sensitive cytochrome c release and activation of external pathway
      of NADH oxidation in liver mitochondria due to pore opening by acidification of
      phosphate-containing incubation medium.
AB  - Acidification of a high phosphate incubation medium from pH 7.4 to 6.5 promotes
      increase in rates of succinate oxidation and exogenous NADH oxidation via
      external (rotenone-and myxothiazol-resistant) pathway by factors 2 and 2.3
      respectively. Cyclosporin A prevents these effects. To measure the cytochrome c
      release, mitochondrial cytochrome c concentration was calculated from absorption
      spectrum of alpha-band of cytochromes c + c1. The cytochrome c release is shown
      to be equal to 27 +/- 4%, 40 +/- 12%, 70 +/- 5% at pH 7.4, 7.0, 6.5,
      respectively, the last value being reduced by cyclosporin A to 10 +/- 3%.
      Immunoblot method gives the similar results. It is concluded that acidification
      of the high phosphate medium induces release of a large part of the cytochrome c
      pool from liver mitochondria due to opening the Ca(2+)-dependent cyclosporin A
      sensitive permeability transition pore and subsequent high amplitude swelling.

PMID- 14570378
TI  - Ligand binding and polymerization characteristics of human milk folate binding
      protein depend on concentration of purified protein and presence of amphiphatic
      substances.
AB  - Two folate binding proteins are present in human milk; one of 27 kDa is a
      cleavage product of the other one (100 kDa) which possesses a hydrophobic
      membrane anchor. A drastic change of radioligand binding characteristics and
      appearance of aggregated weak-radioligand affinity forms on gel filtration
      occurred at low concentrations of both proteins in the absence of Triton X-100 or
      other amphiphatic substances, e.g. cetyltrimethylammonium and phospholipids.
      These findings are consistent with a model predicting association between
      unliganded and liganded monomers resulting in weak-ligand affinity dimers.
      Amphiphatic substances form micelles and lipid bilayers which could separate
      hydrophobic unliganded monomers from hydrophilic liganded monomers (monomers
      become hydrophilic in the liganded state) thereby preventing association between
      these monomeric forms prevailing at low concentrations of the protein. Bio-Gel P
      300 chromatography of the 27 kDa protein revealed a pronounced polymerization
      tendency, which diminished with decreasing protein concentrations, however, not
      in the presence of cetyltrimethylammonium. The data could have some bearings on
      observations indicating that naturally occurring amphiphatic substances,
      cholesterol and phospholipids, are necessary for the important clustering of
      membrane folate receptors.

PMID- 14570379
TI  - Distinct effects of protein kinase C on the barrier function at different
      developmental stages.
AB  - We show here, that activation of protein kinase C by the phorbol ester PMA
      improves barrier function in colon carcinoma (HT 29) cells. By contrast, in
      canine kidney (MDCK I) cells it caused increased permeability and opening of
      tight junctions; the latter has also been noticed in other studies. Thus, with
      PMA confluent HT 29 cells responded with a reduced passage of 330 kDa sodium
      fluorescein, increased transepithelial electrical resistance, and a change in the
      cell shape of the HT 29 cells from an irregular to a regular, hexagonal form.
      Confocal imaging revealed parallel distinct changes in the staining of occludin
      and caludin-1, viz. a translocation from cytoplasmic clusters to apical cell-cell
      contacts. Interestingly, in both cell lines protein kinase A activation caused a
      decreased in the threonine phosphorylation of occludin that correlated with tight
      junction assembly in HT 29 cells and tight junction disassembly in MDCK I cells.
      We conclude that protein kinase C regulation of the epithelial barrier involves
      specific molecular mechanisms and achieves distinct effects at different
      developmental stages.

PMID- 14570381
TI  - Standard outcome metrics and evaluation methodology for disease management
      programs. American Healthways and Johns Hopkins Consensus Conference.
AB  - Disease management is conceptually recognized as being a significant approach for
      closing the gaps in care identified by the Institute of Medicine as contributing
      to poor outcomes from our health care system. That conceptual credibility has
      been bolstered by the disease management industry through the adoption of an
      industry-standard definition of disease management and through the development
      and implementation of disease management accreditation programs by the National
      Committee for Quality Assurance, Utilization Review Accreditation Commission, and
      Joint Commission on Accreditation of Healthcare Organizations. The clinical and
      financial outcomes of disease management programs continue to be suspect,
      however, due to the lack of an industry standard set of outcomes metrics and a
      uniform methodology for evaluating those metrics. As a result, the ability to
      evaluate the effectiveness of any individual program is compromised, and the
      ability to effectively compare results across programs of different delivery
      designs is non-existent. To address this issue, American Healthways and Johns
      Hopkins convened a consensus conference of nearly 150 health care professionals
      representing health plans, hospitals, practicing physicians (both primary care
      and specialty), and other health care professionals. The conference purpose was
      to develop a "first-step" set of metrics and a uniform methodology that could be
      applied industry-wide to enable meaningful comparisons between programs and to
      allow evaluation of individual programs whether "homegrown" or "outsourced." The
      consensus conferees recognized that there were many paths to this objective, but
      that they had to land on a set of metrics and a methodology that was "doable" in
      light of today's technology and data availability. The results of their consensus
      effort follow.

PMID- 14570382
TI  - Risk sharing strategies for disease management programs.

PMID- 14570380
TI  - Participation of chloroplasts in plant apoptosis.
AB  - Mitochondria are known to participate in the initiation of programmed cell death
      (PCD) in animals and in plants. The role of chloroplasts in PCD is still unknown.
      We describe a new system to study PCD in plants; namely, leaf epidermal peels.
      The peel represents a monolayer consisting of cells of two types: phototrophic
      (guard cells) and chemotrophic (epidermal cells). The peels from pea (Pisum
      sativum L.) leaves were treated by cyanide as an inducer of PCD. We found an
      apoptosis-enhancing effect of illumination on chloroplast-containing guard cells,
      but not on chloroplastless epidermal cells. Antioxidants and anaerobiosis
      prevented the CN(-)-induced apoptosis of cells of both types in the dark and in
      the light. On the other hand, methyl viologen and menadione known as ROS
      generating reagents as well as the Hill reaction electron acceptors (BQ, DAD,
      TMPD, or DPIP) that are not oxidized spontaneously by O2 were shown to prevent
      the CN(-)-induced nucleus destruction in guard cells. Apoptosis of epidermal
      cells was potentiated by these reagents, and they had no influence on the CN-
      effect. The light-dependent activation of CN(-)-induced apoptosis of guard cells
      was suppressed by DCMU, stigmatellin or DNP-INT, by a protein kinase inhibitor
      staurosporine as well as by cysteine and serine protease inhibitors. The above
      data suggest that apoptosis of guard cells is initiated upon a combined action of
      two factors, i.e., ROS and reduced plastoquinone of the photosynthetic electron
      transfer chain. As to reduction of ubiquinone in the mitochondrial respiratory
      chain, it seems to be antiapoptotic for the guard cell.

PMID- 14570383
TI  - Framework for assessing causality in disease management programs: principles.
AB  - To credibly state that a disease management (DM) program "caused" a specific
      outcome it is required that metrics observed in the DM population be compared
      with metrics that would have been expected in the absence of a DM intervention.
      That requirement can be very difficult to achieve, and epidemiologists and others
      have developed guiding principles of causality by which credible estimates of DM
      impact can be made. This paper introduces those key principles. First, DM program
      metrics must be compared with metrics from a "reference population." This
      population should be "equivalent" to the DM intervention population on all
      factors that could independently impact the outcome. In addition, the metrics
      used in both groups should use the same defining criteria (ie, they must be
      "comparable" to each other). The degree to which these populations fulfill the
      "equivalent" assumption and metrics fulfill the "comparability" assumption should
      be stated. Second, when "equivalence" or "comparability" is not achieved, the DM
      managers should acknowledge this fact and, where possible, "control" for those
      factors that may impact the outcome(s). Finally, it is highly unlikely that one
      study will provide definitive proof of any specific DM program value for all
      time; thus, we strongly recommend that studies be ongoing, at multiple points in
      time, and at multiple sites, and, when observational study designs are employed,
      that more than one type of study design be utilized. Methodologically
      sophisticated studies that follow these "principles of causality" will greatly
      enhance the reputation of the important and growing efforts in DM.

PMID- 14570384
TI  - Evaluation of decision rules to identify postmenopausal women for intervention
      related to osteoporosis.
AB  - Decision rules for intervention that utilize screening tools for bone mineral
      density (BMD) testing and incorporating the BMD findings and other risk factors
      to identify high-risk women to prevent fracture have not been evaluated. We
      examine the sensitivity and specificity of decision rules for intervention based
      on two pre-BMD screening tools: Simple Calculated Osteoporosis Risk Estimation
      (SCORE) and a Study of Osteoporotic Fractures (SOF)-based tool. Women 60 years of
      age and older without previous osteoporosis diagnosis were randomly selected from
      a managed care population and invited to receive a BMD test. Four hundred sixteen
      women had complete information and were included in the study. Women were
      classified as high risk requiring intervention using three different criteria:
      World Health Organization (t-score -2.5 or less), National Osteoporosis
      Foundation (t-score -2.0 or less, or -1.5 or less with one or more risk factors),
      and the SOF-based criteria (prior fracture; or age 60-64 with t-score less than 
      2.5 or age 65 or older with z-score less than -0.43 and five or more risk
      factors). SCORE identified 82% of the women as appropriate for BMD testing,
      whereas the SOF-based tool identified 26%. Sensitivity and specificity were 89.8%
      96.5% and 23.8%-34.8%, respectively, for the decision rule using SCORE as the
      screening tool and 30.5%-84.9% and 76.0%-95.8%, respectively, for the decision
      rule based on SOF screening criteria. SCORE correctly identified more women who
      were at high risk for intervention, whereas the SOF-based tool correctly
      identified more women who do not meet intervention criteria. The appropriate
      selection of a screening tool depends upon the objective for intervention and
      trade-off between not identifying women for BMD testing who are at high risk and
      identifying more women for BMD testing who are at low risk.

PMID- 14570385
TI  - Uncontrolled chronic disease: patient non-compliance or clinical mismanagement?
AB  - A study group of 30 individuals was randomly chosen from 1,379 beneficiaries
      predicted to be at risk for health care complications at a large, Midwest,
      industrial company currently experiencing increased health care costs. All 30
      individuals had one or more chronic illness, primarily diabetes, cardiovascular
      disease, or asthma. Through analysis of medical records, a self-reporting health
      risk assessment survey, and personal contact with both patients and clinicians,
      each study individual was assessed as to whether his disease(s) was under
      control, the individual was compliant with his treatment protocol, and whether
      the supervising clinician was following nationally accepted standards of care.
      Fewer than 50% of the individuals in the study group had their chronic
      illness(es) under control. Those individuals whose treatment adhered to national
      guidelines were significantly more likely to have their disease under control (p
      < 0.001). For this study, patient compliance was high and unrelated to whether
      their disease was under control. Behavioral (external) barriers were most often
      cited as the reason a clinical practitioner did not follow the appropriate
      national standard of care. Most clinicians were aware of and familiar with the
      guidelines; a few either did not agree with or misunderstood the guidelines. The
      results of this study suggest that changing clinical practice behaviors to better
      ensure compliance to national standards of care may make a substantial difference
      in chronic disease control.

PMID- 14570386
TI  - A novel approach for mental health disease management: the Air Force Medical
      Service's interdisciplinary model.
AB  - Mental health disorders are one of the most substantial public health problems
      affecting society today, accounting for roughly 15% of the overall burden of
      disease from all causes in the United States. Although primary care (PC) has the
      potential to be the frontline for recognition and management of behavioral health
      conditions, this has been a challenge historically. In order to more effectively
      address the broad scope of behavioral health needs, the Air Force Medical Service
      (AFMS) established a new model of behavioral health care. Through a series of
      coordinated steps, the AFMS ultimately placed trained behavioral health providers
      into PC clinics to serve as consultants to PC providers (PCPs). Behavioral Health
      Consultants (BHCs) provide focused assessments, present healthcare options to
      patients, and deliver brief collaborative interventions in the PC setting. BHCs
      see patients at the request of the PCP, in 15-30-min appointments. In the pilot
      study, patients averaged 1.6 visits to the BHC. Over 70% of patients fell into
      six categories of presenting problems: situational reactions, depressive
      disorders, adjustment disorders, anxiety disorders, health promotion, and
      obesity. Patient data (n = 76) suggest 97% of patients seen were either
      "satisfied" or "very satisfied" with BHC services, and 100% of the PCPs (n = 23,
      68% response rate) were highly satisfied and indicated they would "definitely
      recommend" others use BHC services for their patients. Both the implications and
      the limitations of this pilot study are discussed.

PMID- 14570387
TI  - Utilizing pharmacists in collaborative diabetes disease state management.

PMID- 14570388
TI  - Bioenergetics and transmitter release in the isolated nerve terminal.
AB  - The isolated nerve terminal (or synaptosome) is the simplest preparation that
      allows mitochondrial bioenergetics to be studied in a physiological milieu, as
      well as facilitating investigation of the protein chemistry and regulation of
      synaptic vesicle exocytosis and recovery and providing a target for the study of
      the mechanism of action of numerous neurotoxins. This brief review discusses
      studies from our laboratory that may have provided some insight into these
      aspects of nerve terminal function.

PMID- 14570390
TI  - Differential expression of syntaxin 1A and 1B by noradrenergic and adrenergic
      chromaffin cells.
AB  - The expression and localization of syntaxin isoforms 1A and 1B in adrenergic and
      noradrenergic chromaffin cells were examined by both immunoblot analysis and
      confocal immunofluorescence microscopy. Syntaxin 1A was found in higher levels in
      noradrenergic cells, whereas syntaxin 1B was similarly expressed in most
      noradrenergic and adrenergic cells. However, some heterogeneity was observed
      within each catecholaminergic phenotype. Although the majority of adrenergic
      cells appeared to express low levels of syntaxin 1A, about 7% was strongly
      stained for syntaxin 1A. A subpopulation of noradrenergic cells, about 17%,
      expressed greater levels of syntaxin 1B. Syntaxin 1B labeling showed a punctate
      appearance in the cytoplasm, whereas syntaxin 1A appeared predominantly localized
      to the plasma membrane. These data show differences in the exocytotic machinery
      of the two subtypes of chromaffin cells that may underlie some of the distinct
      characteristics of adrenaline and noradrenaline secretion.

PMID- 14570389
TI  - Regulation of vesicle traffic and neurotransmitter release in isolated nerve
      terminals.
AB  - In this overview current insights in the regulation of presynaptic transmitter
      release, mainly acquired in studies using isolated CNS nerve terminals are
      highlighted. The following aspects are described. (i) The usefulness of pinched
      off nerve terminals, so-called synaptosomes, for biochemical and ultrastructural
      studies of presynaptic stimulus-secretion coupling. (ii) The regulation of
      neurotransmitter release by multiple Ca2+ channels, with special emphasis on the
      specificity of different classes of these channels with respect to the release of
      distinct types of neurotransmitters, that are often co-localized, such as amino
      acids and neuropeptides. (iii) Possible molecular mechanisms involved in
      targeting synaptic vesicle (SV) traffic toward the active zone. (iv) The role of
      presynaptic receptors in regulating transmitter release, with special emphasis on
      different glutamate subtype receptors. Isolated nerve terminals are of great
      value as model system in order to obtain a better understanding of the regulation
      of the release of distinct classes of neurotransmitters in tiny CNS nerve
      endings.

PMID- 14570391
TI  - Regulation of AMPA receptor activity, synaptic targeting and recycling: role in
      synaptic plasticity.
AB  - The alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors for
      the neurotransmitter glutamate are oligomeric structures responsible for most
      fast excitatory responses in the central nervous system. The activity of AMPA
      receptors can be directly regulated by protein phosphorylation, which may also
      affect the interaction with intracellular proteins and, consequently, their
      recycling and localization to defined postsynaptic sites. This review focuses on
      recent advances in understanding the dynamic regulation of AMPA receptors, on a
      short- and long-term basis, and its implications in synaptic plasticity.

PMID- 14570392
TI  - Local differences in GABA release induced by excitatory amino acids during retina
      development: selective activation of NMDA receptors by aspartate in the inner
      retina.
AB  - Glutamate and GABA are the major excitatory and inhibitory neurotransmitters in
      the CNS. In the retina, it has been shown that glutamate and aspartate and their
      agonists kainate and NMDA promote the release of GABA. In the chick retina, at
      embryonic day 14 (E14), glutamate and kainate were able to induce the release of
      GABA from amacrine and horizontal cells as detected by GABA-immunoreactivity.
      NMDA also induced GABA release restricted to amacrine cell population and its
      projections to the inner plexiform layer (E14 and E18). Although aspartate
      reduced GABA immunoreactivity, specifically in amacrine cells of E18 retinas, it
      was not efficient to promote GABA release from retinas at E14. As observed in
      differentiated retinas, dopamine inhibited the GABA release promoted by NMDA and
      aspartate but not by kainate. Our data show that different retinal sites respond
      to distinct EAAs via different receptor systems.

PMID- 14570393
TI  - Mechanisms underlying domoic acid-induced dopamine release from striatum: an in
      vivo microdialysis study.
AB  - The brain microdialysis technique has been used to examine the in vivo effects of
      the neurotoxin domoic acid (an ionotropic glutamate receptor agonist) on dopamine
      (DA) release in the striatum of conscious and freely moving rats. Local
      application of domoic acid (500 microM) through the microdialysis probe produced
      an increase in striatal DA content (597 +/- 96% with respect to basal levels).
      The release of DA induced by domoic acid was not attenuated in a Ca(+2)-free
      medium (469 +/- 59%) or after pretreatment with 10 mg/kg reserpine (533 +/- 79%).
      Intrastriatal infusion of 1 microM tetrodotoxin (TTX) partially reduced the
      domoic acid-evoked DA release (278 +/- 34%). Moreover, domoic acid perfusion had
      no effect on K+-evoked DA release. The results suggest that domoic acid increases
      the striatal DA release according to a reserpine-independent, calcium-independent
      and partially TTX-insensitive mechanism, suggesting that these effects probably
      involve a nonexocytotic process. On the other hand, the inhibitor of DA uptake
      nomifensine (10 microM) reduced the domoic acid-evoked DA release (356 +/- 59%),
      suggesting that a carrier-dependent mechanism could be involved in the effect of
      domoic acid on the striatal DA levels.

PMID- 14570394
TI  - AMPA receptor-mediated neurotoxicity: role of Ca2+ and desensitization.
AB  - Glutamate-induced neurodegeneration is the result of excessive stimulation of the
      different subtypes of glutamate receptors. With regard to the AMPA ((RS)-2-amino
      3-(3-hydroxy-5-methylisoxazol-4-yl)propionate) receptors it has been clear from
      numerous studies that in addition to the Ca2+ permeability of the receptor
      complexes, their desensitization properties may play a determining role in the
      neurodegeneration mediated by this subtype of the glutamate receptors. Recent
      studies have revealed important amino acid residues in the AMPA receptor subunits
      that control the desensitization kinetics and that may constitute important
      targets for drugs that may alter the desensitization of the AMPA receptor
      complexes.

PMID- 14570396
TI  - Epilepsy, neurodegeneration, and extracellular glutamate in the hippocampus of
      awake and anesthetized rats treated with okadaic acid.
AB  - We have previously shown that the intrahippocampal microinjection of okadaic acid
      (OKA), a potent inhibitor of serine/threonine protein phosphatases, induces
      epileptic seizures, neuronal death, and the hyperphosphorylation of the NR2B
      subunit of the N-methyl-D-aspartate (NMDA) receptor. We administered OKA by
      reverse microdialysis in the hippocampus of awake and halothane-anesthetized
      rats, with simultaneous collection of microdialysis fractions and recording of
      the EEG activity, and subsequent histological analysis. OKA produced intense
      behavioral and persistent EEG seizure activity in the awake rats but not in the
      anesthetized animals, and did not significantly alter the extracellular
      concentration of glutamate and aspartate detected in the microdialysis fractions.
      One day after the experiment a remarkable neurodegeneration of CA1 hippocampal
      region was observed in both the awake and the anesthetized rats. We conclude that
      the OKA-induced epilepsy cannot be ascribed to increased extracellular glutamate,
      but to an increased sensitivity of NMDA receptor. We propose that halothane
      protected against the epilepsy because it blocks NMDA receptor overactivation,
      and that the neurodegeneration of CA1 region is independent of this
      overactivation and due probably to alterations of cytoskeletal proteins
      consequent to the OKA-induced hyperphosphorylation.

PMID- 14570397
TI  - Zinc and energy requirements in induction of oxidative stress to retinal
      pigmented epithelial cells.
AB  - In age-related macular degeneration (AMD), retinal pigmented epithelium (RPE)
      cells are believed to be detrimentally affected. It is thought that zinc may play
      a part in this process. In the past, therefore, zinc supplementation has been
      suggested as a treatment for AMD. Experimental data shown here confound this view
      by indicating that whereas low amounts of zinc do protect RPE cells in culture
      from stress-induced effects, greater amounts of zinc have the opposite influence.
      These effects are partly dependent upon the "health status" of the cells.
      Experimental data presented herein also show that zinc-induced death of RPE cells
      can, however, be attenuated by compounds such as antioxidants (alpha-tocopherol,
      trolox, and metipranolol), or cellular energy substrates (pyruvate and
      oxaloacetate). It is therefore concluded that a combination of zinc and
      antioxidants or energy substrates rather that zinc alone should provide a safer
      and more effective way to treat a disease such as AMD.

PMID- 14570398
TI  - Reversibility of cisternal stack formation during hypoxic hypoxia and subsequent
      reoxygenation in cerebellar Purkinje cells.
AB  - Cisternal stacks are induced during hypoxia, which may be associated with
      intracellular Ca2+ regulation. Although neurons are divided internally in
      different compartments, little is known about regional differences in cisternal
      stack formation. We investigated the effects of hypoxic hypoxia and later
      reoxygenation on cisternal stack formation and other ultrastructual changes in
      the proximal dendrite, dendritic spine, and cell body of cerebellar Purkinje
      cells in rats. After brief hypoxic events, cisternal stacks appeared
      predominantly in the proximal dendrites and after longer hypoxic events in
      dendritic spines and cell body. Following reoxygenation, cisternal stacks
      disappeared first in the cell body, followed by the dendritic spines, then the
      proximal dendrites. These results showed that stack formation occurred at
      different degrees and time courses among the three regions, and the effect was
      reversible, which suggests that these compartments are differentially sensitive
      to hypoxia.

PMID- 14570395
TI  - Presynaptic modulation controlling neuronal excitability and epileptogenesis:
      role of kainate, adenosine and neuropeptide Y receptors.
AB  - Based on the idea that seizures may arise from an overshoot of excitation over
      inhibition, all substances that may decrease glutamatergic function while having
      no effect or even increasing GABAergic neurotransmission are likely to be
      effective anticonvulsants. We now review the possible role of three such
      neuromodulators, kainate, adenosine, and neuropeptide Y receptors in controlling
      hyperexcitability and epileptogenesis. Particular emphasis is given on the robust
      neuromodulatory role of these three groups of receptors on the release of
      glutamate in the hippocampus, a main focus of epilepsy. Moreover, we also give
      special attention to the mechanisms of receptor activation and coupled signaling
      events that can be explored as attractive targets for the treatment of epilepsy
      and excitotoxicity. The present paper is a tribute to Arselio Pato de Carvalho
      who has been the main driving force for the development of Neuroscience in
      Portugal, notably with a particular emphasis on the presynaptic mechanisms of
      modulation of neurotransmitter release.

PMID- 14570399
TI  - Intracellular calcium homeostasis changes induced in rat spinal cord neurons by
      extracellular acidification.
AB  - Changes in intracellular Ca2+ induced by extracellular acidification to pH = 6
      were studied in isolated rat spinal dorsal horn neurons using indo-1 fluorescent
      technique. In all neurons such treatment induced a decrease of basal [Ca2+]i
      level by 20.8%, preceded in some of them by temporary increase. The changes were
      completely reversible. The depolarization-induced [Ca2+]i transients became
      strongly and also reversibly depressed. If tested after termination of
      acidification, they demonstrated substantial prolongation of their decay phase,
      reaching 310% at 120 sec after the application of depolarization. To analyze the
      mechanisms of such changes, mitochondrial protonophore CCCP has been applied
      between the end of acidification and the depolarizing pulse. This completely
      eliminated the described slowing of the transients' decay. To the contrary,
      application of caffeine to induce Ca2+ release from the endoplasmic reticulum did
      not show significant changes in the corresponding [Ca2+]i transients. A
      conclusion is made that in mammalian neurons extracellular acidification, apart
      from inhibiting voltage-operated Ca2+ channels, also substantially alters the
      Ca2+ exchange function of mitochondria responsible for rapid accumulation of ions
      and their delayed release back into the cytosol.

PMID- 14570400
TI  - A metabolic basis for Alzheimer disease.
AB  - Most studies of Alzheimer's disease (AD) have focused on a single precipitating
      alteration as the etiological event rather than global changes closely linked to
      aging. Recent evidence suggests that the most significant of these global changes
      are metabolic. Here we present data indicating that metabolic rate, nutrition,
      and neuronal size are all early indicators of AD. Understanding the cellular and
      molecular basis for these changes may open a new dimension to understanding AD.

PMID- 14570401
TI  - Protein phosphorylation and APP metabolism.
AB  - Numerous lines of evidence place signal transduction cascades at the core of many
      processes having a direct role in neurodegeneration and associated disorders. Key
      players include neurotransmitters, growth factors, cytokines, hormones, and even
      binding and targeting proteins. Indeed, abnormal phosphorylation of key control
      proteins has been detected in many cases and is thought to underlie the
      associated cellular dysfunctions. Several signaling cascades have been
      implicated, affecting processes as varied as protein processing, protein
      expression, and subcellular protein localization, among others. The Alzheimer's
      amyloid precursor protein (APP) is a phosphoprotein, with well-defined
      phosphorylation sites but whose function is not clearly understood. The factors
      and pathways regulating the processing of APP have been particularly elusive,
      both in normal ageing and the Alzheimer's disease (AD) condition. Not
      surprisingly, the physiological function(s) of the protein remain(s) to be
      elucidated, although many hypotheses have been advanced. Nonetheless,
      considerable data has accumulated over the last decade, placing APP in key
      positions to be modulated both directly and indirectly by phosphorylation and
      phosphorylation-dependent events. The pathological end product of APP processing
      is the main proteinaceous component of the hallmark senile plaques found in the
      brains of AD patients, that is, a toxic peptide termed Abeta. In this minireview
      we address the importance of phosphorylation and signal transduction cascades in
      relation to APP processing and Abeta production. The possible use of the
      identified molecular alterations as therapeutic targets is also addressed.

PMID- 14570402
TI  - Mitochondrial dysfunction and reactive oxygen species in excitotoxicity and
      apoptosis: implications for the pathogenesis of neurodegenerative diseases.
AB  - In recent years we have witnessed a major interest in the study of the role of
      mitochondria, not only as ATP producers through oxidative phosphorylation but
      also as regulators of intracellular Ca2+ homeostasis and endogenous producers of
      reactive oxygen species (ROS). Interestingly, the mitochondria have been also
      implicated as central executioners of cell death. Increased mitochondrial Ca2+
      overload as a result of excitotoxicity has been associated with the generation of
      superoxide and may induce the release of proapoptotic mitochondrial proteins,
      proceeding through DNA fragmentation/condensation and culminating in cell demise
      by apoptosis and/or necrosis. In addition, these processes have been implicated
      in the pathogenesis of many neurodegenerative diseases, which share several
      features of cell death: selective brain areas undergo neurodegeneration,
      involving mitochondrial dysfunction (mitochondrial complexes are affected), loss
      of intracellular Ca2+ homeostasis, excitotoxicity, and the extracellular or
      intracellular accumulation of insoluble protein aggregates in the brain.

PMID- 14570403
TI  - The production of reactive oxygen species in intact isolated nerve terminals is
      independent of the mitochondrial membrane potential.
AB  - Dependence on mitochondrial membrane potential (deltapsim) of hydrogen peroxide
      formation of in situ mitochondria in response to inhibition of complex I or III
      was studied in synaptosomes. Blockage of electron flow through complex I by
      rotenone or that through complex III by antimycin resulted in an increase in the
      rate of H2O2 generation as measured with the Amplex red assay. Membrane potential
      of mitochondria was dissipated by either FCCP (250 nM) or DNP (50 microM) and
      then the rate of H2O2 production was followed. Neither of the uncouplers had a
      significant effect on the rate of H2O2 production induced by rotenone or
      antimycin. Inhibition of the F0F1-ATPase by oligomycin, which also eliminates
      deltapsim in the presence of rotenone and antimycin, respectively, was also
      without effect on the ROS formation induced by rotenone and only slightly reduced
      the antimycin-induced H2O2 production. These results indicate that ROS generation
      of in situ mitochondria in nerve terminals in response to inhibition of complex I
      or complex III is independent of deltapsim. In addition, we detected a
      significant antimycin-induced H2O2 production when the flow of electrons through
      complex I was inhibited by rotenone, indicating that the respiratory chain of in
      situ mitochondria in synaptosomes has a substantial electron influx distal from
      the rotenone site, which could contribute to ROS generation when the complex III
      is inhibited.

PMID- 14570404
TI  - Adenosine regulates the survival of avian retinal neurons and photoreceptors in
      culture.
AB  - Adenosine modulates the survival of chick embryo retinal neurons in culture. When
      cultures were incubated for 3 days and refed with fresh medium, a large
      proportion of neurons died in the subsequent 3 days of culture. This cell death
      was prevented by preincubation of cultures for at least 24 h with adenosine plus
      the adenosine deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA),
      an adenosine uptake blocker nitrobenzylthioinosine (NBI), the adenosine A2A
      receptor agonist 2-[4-(2-carboxyethyl) phenethylamino]-5'-N
      ethylcarboxamidoadenosine (CGS21680), or the permeant cyclic AMP analog 8-bromo
      cyclic AMP, but not the A1 receptor agonist cyclohexyladenosine (CHA). Adenosine
      deaminase induced cell death when added to culture medium, and this effect was
      prevented by EHNA. Cell death was not observed when the medium was replaced by a
      conditioned medium from sister cultures. The data strongly suggest that adenosine
      regulates the survival of developing retinal neurons by a long-term activation of
      A2A receptors and the increase of cyclic AMP levels.

PMID- 14570405
TI  - Endogenous adenosine modulation of 22Na uptake by rat brain synaptosomes.
AB  - To evaluate if endogenous extracellular adenosine influences sodium channel
      activity in nerve terminals, we investigated how manipulations of extracellular
      adenosine levels influence 22Na uptake by rat brain synaptosomes stimulated with
      veratridine (VT). To decrease extracellular adenosine levels, adenosine deaminase
      (ADA) that converts adenosine into an inactive metabolite was used. To increase
      extracellular adenosine levels, we used the adenosine deaminase inhibitor erythro
      9(2-hydroxy-3-nonyl) adenine (EHNA), as well as the inhibitor of adenosine
      transport, nitrobenzylthioinosine (NBTI). ADA (0.1-5 U/ml) caused an excitatory
      effect on 22Na uptake stimulated by veratridine, which was abolished in the
      presence of the adenosine deaminase inhibitor erythro-9(2-hydroxy-3-nonyl)
      adenine (EHNA, 25 microM). Both the adenosine uptake inhibitor
      nitrobenzylthioinosine (NBTI, 1-10 microM) and the adenosine deaminase inhibitor
      EHNA (10-25 microM) inhibited 22Na uptake by rat brain synaptosomes. It is
      suggested that adenosine is tonically inhibiting sodium uptake by rat brain
      synaptosomes.

PMID- 14570407
TI  - Sodium channel toxins and neurotransmitter release.
AB  - Voltage-dependent sodium channels (VDSC) are an important class of ion channels
      in excitable cells, where they are responsible for the generation and conduction
      of action potential. In addition, the release of neurotransmitters from nerve
      terminals is influenced by sodium channel activity. The function of VDSC is
      subject to modulation by various neurotoxins, such as scorpion toxins, which have
      long been used as tools in the investigation of neurotransmitter release. This
      opens an interesting perspective concerning modulation of neurotransmission via
      pharmacological manipulation of sodium channel properties, which can lead to a
      better understanding of their physiological and pathological roles. Here we
      briefly review the studies of neurotoxins acting on sodium channels, focusing
      primarily on the view of the mechanisms of neurotransmitter release.

PMID- 14570408
TI  - Monitoring the results of Canada/U.S.A. acid rain control programs: some lake
      responses.
AB  - Aquatic acidification by deposition of airborne pollutants emerged as an
      environmental issue in southeastern Canada during the 1970s. Drawing information
      from the extensive research and monitoring programs, a sequence of issue
      assessments demonstrated the necessity of reducing the anthropogenic emissions of
      acidifying pollutants, particularly sulphur dioxide (SO2). The 1991 Canada-U.S.
      Air Quality Agreement (AQA) was negotiated to reduce North American SO2 emissions
      by approximately 40% relative to 1980 levels by 2010, and at present, both
      countries have reduced emissions beyond their AQA commitment. In response to
      reduced SO2 emissions, atmospheric deposition of sulphate (SO4(2-)) and SO4(2-)
      concentrations in many lakes have declined, particularly in south-central Ontario
      and southern Quebec. Sulphate deposition still exceeds aquatic critical loads
      throughout southeastern Canada however. Increasing pH or alkalinity (commonly
      deemed 'recovery') has been observed in only some lakes. Several biogeochemical
      factors have intervened to modify the lake chemistry response to reduced SO4(2-)
      input, notably release of stored SO4(2-) from wetlands following periods of
      drought and reduction in the export of base cations from terrestrial soils. Three
      examples from Ontario are presented to illustrate these responses. Significant
      increases in pH and alkalinity have been observed in many lakes in the Sudbury
      area of Ontario due to the large reductions in local SO2 emissions; 'early-stage'
      biological recovery is evident in these lakes. An integrated assessment model
      predicts that AQA emission reductions will not be sufficient to promote
      widespread chemical or biological recovery of Canadian lakes. Monitoring and
      modeling are mutually supporting assessment activities and both must continue.

PMID- 14570406
TI  - P2X7 receptors in rat brain: presence in synaptic terminals and granule cells.
AB  - ATP stimulates [Ca2+]i increases in midbrain synaptosomes via specific ionotropic
      receptors (P2X receptors). Previous studies have demonstrated the implication of
      P2X3 subunits in these responses, but additional P2X subunits must be involved.
      In the present study, ATP and BzATP proved to be able to induce intrasynaptosomal
      calcium transients in the midbrain synaptosomes, their effects being potentiated
      when assayed in a Mg2+-free medium. Indeed, BzATP was shown to be more potent
      than ATP, and their effects could be inhibited by PPADS and KN-62, but not by
      suramin. This activity profile is consistent with the presence of functional P2X7
      receptors in the midbrain terminals. The existence of presynaptic responses to
      selective P2X7 agonists could be confirmed by means of a microfluorimetric
      technique allowing [Ca2+]i measurements in single synaptic terminals.
      Additionally, the P2X7 receptor protein could be identified in the midbrain
      synaptosomes and in axodendritic prolongations of cerebellar granule cells by
      immunochemical staining.

PMID- 14570409
TI  - Inter- and intra-annual chemical variability during the ice-free season in lakes
      with different flushing rates and acid deposition histories.
AB  - Quantifying chemical variability in different lake types is important for the
      assessment of both chemical and biological responses to environmental change. For
      monitoring programs that emphasize a large number of lakes at the expense of
      frequent samples, high variability may influence how representative single
      samples are of the average conditions of individual lakes. Intensive temporal
      data from long-term research sites provide a unique opportunity to assess
      chemical variability in lakes with different characteristics. We compared the
      intra- and inter-annual variability of four acidification related variables (Gran
      alkalinity, pH, sulphate concentration, and total base cation concentration) in
      four lakes with different flushing rates and acid deposition histories.
      Variability was highest in lakes with high flushing rates and was not influenced
      by historic acid deposition in our study lakes. This has implications for the
      amount of effort required in monitoring programs. Lakes with high flushing rates
      will require more frequent sampling intervals than lakes with low flushing rates.
      Consideration of specific lake types should be included in the design of
      monitoring programs.

PMID- 14570410
TI  - Changes in acid precipitation-related water chemistry of lakes from southwestern
      New Brunswick, Canada, 1986-2001.
AB  - Between 1986 and 2001, thirty-nine lakes in southwestern New Brunswick in
      Atlantic Canada were surveyed for acid precipitation-related water quality
      changes. Most of the study lakes are located on granite bedrock and represent the
      most acid sensitive lakes in the province. Between 1987 and 1992, hydrogen ion
      deposition to the lake study area averaged 452 eq ha(-1) yr(-1), compared to 338
      eq ha(-1) yr(-1) between 1993 and 2000, a 25% reduction. The lake chemistry data
      were evaluated by dividing the lakes into four clusters for each survey year
      based on their acid neutralizing capacity. Twenty percent of the lakes (cluster
      IV) had an average ANC of 40 microeq L(-1) or greater and maintained an average
      pH of greater than 6 over the duration of the study period. A pH of 6 or greater
      is considered a healthy benchmark for maintaining biodiversity. The remaining 31
      lakes (clusters I to III) had an average ANC of less than 40 microeq L(-1) and
      maintained an average pH of less than 6. Other lake chemistry changes included a
      general decline in lake sulphate and colour over the duration of the survey
      period, followed by more recent improvements in calcium ion, pH and ANC, and
      notably higher but declining aluminum levels in lower ANC and pH lakes. Nitrate
      accounted for 37% of the acid deposition to the study area, however it was not
      detectable in the lakes. Although acid deposition has declined and these lakes
      are beginning to show signs of acid recovery, 80% of the study lakes remain acid
      sensitive having little buffering capacity with low calcium, pH and ANC.

PMID- 14570411
TI  - Assessing potential for recovery of biotic richness and indicator species due to
      changes in acidic deposition and lake pH in five areas of southeastern Canada.
AB  - Biological damage to sensitive aquatic ecosystems is among the most recognisable,
      deleterious effects of acidic deposition. We compiled a large spatial database of
      over 2000 waterbodies across southeastern Canada from various federal, provincial
      and academic sources. Data for zooplankton, fish, macroinvertebrate (benthos) and
      loon species richness and occurrence were used to construct statistical models
      for lakes with varying pH, dissolved organic carbon content and lake size. pH
      changes, as described and predicted using the Integrated Assessment Model (Lam et
      al., 1998; Jeffries et al., 2000), were based on the range of emission reductions
      set forth in the Canada/US Air Quality Agreement (AQA). The scenarios tested
      include 1983, 1990, 1994 and 2010 sulphate deposition levels. Biotic models were
      developed for five regions in southeastern Canada (Algoma, Muskoka, and Sudbury,
      Ontario, southcentral Quebec, and Kejimkujik, Nova Scotia) using regression tree,
      multiple linear regression and logistic regression analyses to make predictions
      about recovery after emission reductions. The analyses produced different
      indicator species in different regions, although some species showed consistent
      trends across regions. Generally, the greatest predicted recovery occurred during
      the final phase of emission reductions between 1994 and 2010 across all taxonomic
      groups and regions. The Ontario regions, on average, were predicted to recover to
      a greater extent than either southcentral Quebec or the Kejimkujik area of Nova
      Scotia. Our results reconfirm that pH 5.5-6.0 is an important threshold below
      which damage to aquatic biota will remain a major local and regional
      environmental problem. This damage to biodiversity across trophic levels will
      persist well into the future if no further reductions in sulphate deposition are
      implemented.

PMID- 14570412
TI  - Ecological monitoring for assessing the state of the nearshore and open waters of
      the Great Lakes.
AB  - The Great Lakes Water Quality Agreement stipulates that the Governments of Canada
      and the United States are responsible for restoring and maintaining the chemical,
      physical and biological integrity of the waters of the Great Lakes Basin
      Ecosystem. Due to varying mandates and areas of expertise, monitoring to assess
      progress towards this objective is conducted by a multitude of Canadian and U.S.
      federal and provincial/state agencies, in cooperation with academia and regional
      authorities. This paper highlights selected long-term monitoring programs and
      discusses a number of documented ecological changes that indicate the present
      state of the open and nearshore waters of the Great Lakes.

PMID- 14570413
TI  - The development and implementation of indicators of ecosystem health in the Great
      Lakes basin.
AB  - This paper describes a process for the selection of a suite of ecosystem health
      indicators for the Great Lakes, as called for in the Great Lakes Water Quality
      Agreement. The paper also presents some preliminary data on status and trends in
      ecosystem components based on those indicators. The indicator selection process
      was carried out by over 150 scientists and managers from both Canada and the USA,
      and involved the presentation of the proposed indicators at the State of the
      Lakes Ecosystem Conferences (SOLECs). An open period for comment followed the
      conferences where input from scientists involved in Great Lakes programs was
      received. The suite of indicators will, over time, present information in an
      understandable format that will allow for more informed management decisions.

PMID- 14570414
TI  - Seabirds as indicators of changes in marine ecosystems: ecological monitoring on
      Machias Seal Island.
AB  - Changes in marine ecosystems can be manifested in many different ways, on
      different temporal and spatial scales. Seabirds are top consumers in marine
      foodwebs and offer opportunities to detect and assess the biological effects of
      changes in physical parameters (sea-surface temperature [SST], salinity, depth of
      thermocline etc.) of the marine ecosystem. We compare six-eight years' of data on
      the biology (diet, and breeding success) of four species of seabird (arctic tern
      Sterna paradisaea and common tern S. hirundo, which feed at the sea surface; and
      Atlantic puffin Fratercula antica and razorbill Alca torda, which dive 30-60 m
      for their prey) breeding on Machias Seal Island (MSI) in the Bay of Fundy with
      both our own meteorological and oceanographic measurements, and with standard
      measurements from conventional sources. These are compared with fisheries data on
      changes in the main prey of all the seabirds concerned (juvenile or '0-group'
      herring Clupea harengus) which are the most direct link between the seabirds and
      the physical properties of the marine system. We explore relationships between
      seabird productivity and diet, and other aspects of both herring biology (larval
      surveys, and fat content) and oceanography (SST data from the island, and
      remotely sensed data from the entrance to the Bay of Fundy). Timing of laying by
      puffins followed SST variation at neither the local (MSI) nor regional scales,
      but at the scale of the North Atlantic, following the trend of populations
      breeding off northern Norway. The proportion of herring in the diet of terns over
      6 years varied inversely with herring larval abundance the previous fall; this
      relationship was not statistically significant in the puffin and razorbill. A
      major new finding is the considerable (approximately 50%) inter-annual variation
      in the energy density (fat content) of juvenile herring that are the main seabird
      prey; breeding success of both species of tern varied in parallel with the energy
      density of juvenile herring in the diet until the last two years of the study,
      when sandlance (Ammodytes sp.) and euphausid shrimp predominated in the diet. Our
      long-term research approach combines traditional population monitoring (of
      numbers of breeding birds) with demographic, behavioural and environmental
      monitoring, to provide new understanding of the marine ecosystem as well as of
      seabirds.

PMID- 14570415
TI  - Knowing, mapping and understanding St. Lawrence biodiversity, with special
      emphasis on bird assemblages.
AB  - Environment Canada and the Quebec Department of the Environment, partners in the
      St Lawrence Vision 2000 Action Plan, set out to prepare a compendium of knowledge
      of the flora and fauna of the St Lawrence and to identify potential conservation
      sites. The resulting Portrait is an Internet site that presents the current
      knowledge base of the river's ecological and biological diversity
      (http://lavoieverte.qc.ec.gc.ca/faune/biodiv/index.html). The Portrait provides
      information on over 5,000 species of flora and fauna. On the website, you will
      find a detailed ecological analysis of the richness, rarity and vulnerability of
      several broad groups of plant and animal species. Furthermore, you will find a
      list of species for each of the 700 survey units and a distribution map for 2,500
      species recorded along the St Lawrence., in atlas form, along with a detailed
      conservation plan. The plan encompasses the most unique and heterogeneous
      landscapes of the St Lawrence, some of which have no protection at present. The
      Portrait provides an overview of the sites that are currently protected by public
      agencies and private-sector organisations and identifies new sites of interest
      for conserving biodiversity and protecting species at risk. This paper exposes
      the content of this extensive compendium on the biodiversity of the St. Lawrence.
      For conciseness, it presents some of the analyses conducted on birds to
      illustrate a few of the analytical approaches that were used. Then, the
      information on species richness and concentration areas for priority species of
      vascular plants, breeding birds and herpetofauna will serve to identify the
      terrestrial sites of significance for biodiversity. Finally, a similar approach
      having been applied to the aquatic environnement, we will conclude with a
      conservation plan that identifies the terrestrial and aquatic ecosystems, and the
      geographic sites where the most important elements of St. Lawrence biodiversity
      are concentrated. Our analysis of the biodiversity of the most thoroughly studied
      taxa of the St. Lawrence clearly shows the importance of wetlands, particularly
      those located at the mouths of rivers or within archipelagos or delta complexes,
      such as the groups of islands and channels found at both ends of the Montreal
      Archipelago. These aquatic landscapes are sites of intense biological production,
      combining in a small geographical area spawning, nursery and feeding grounds for
      a large number of fish species and breeding, rearing and foraging areas for
      aquatic birds. Variable flooding conditions, associated with seasonal flooding or
      daily tidal fluctuations, create a complex mosaic of wetland and aquatic
      habitats. Although wetlands occupy only a small area in comparison with
      terrestrial habitats, they support a large number of rare plant and animal
      species in relation to their size. At present, 10% of the vascular flora and 27%
      of the herpetofauna of the St. Lawrence are at risk. In the case of reptiles and
      amphibians, the situation is especially worrisome because nearly all of the most
      threatened species live in a narrow band along the river corridor. Not only is
      this the sector that is under the greatest pressure from human development, very
      little public land remains here, making it difficult to create protected areas.
      Increased participation by non-governmental organisations and individuals,
      through private stewardship arrangements, is an essential precondition for
      completing the network of conservation areas in this part of the St. Lawrence.
      Along the estuary and the Gulf, habitat integrity has not been affected as much
      by the expansion of Quebec's human population. This is a vast territory, and
      sites have been identified with a view to making up for the deficiencies in the
      present network of protected sites in terms of representing biodiversity.

PMID- 14570416
TI  - Metal contamination in zebra mussels (Dreissena polymorpha) along the St.
      Lawrence River.
AB  - In order to evaluate the use of zebra mussels as biomonitors for metal
      bioavailability in the St. Lawrence River, we tested the hypothesis that the
      concentrations of 11 metals in zebra mussels vary significantly between sites
      along the river and that the season of collection and body size affect metal
      bioaccumulation. Mussels were collected at 14 sites during June 1996 and at
      monthly intervals at one site. Specimens were grouped in three size classes and
      their soft tissue was analyzed for As, Ca, Cd, Cr, Hg, Mn, Ni, Pb, Se, and Zn.
      Significant size effects were found for Ca, Cd, Cr, Cu, Ni and Zn. Spatial and
      seasonal variations in bioconcentration were significant for all metals. Spatial
      patterns in contamination that corresponded to known point sources of pollution
      or hydrology of the river were identified by principal component analysis.
      Seasonal variations can be attributed to the reproductive cycle of mussels and
      hydrological variability of the river. In comparison with values reported for
      zebra mussels in other contaminated sites in North America and Europe, levels of
      metal in the St. Lawrence River are low or intermediate. Our results show that
      when controlled for size and seasonal effects, zebra mussels represent a useful
      biomonitor for metal availability in the river and may offer an interesting
      alternative to native mussels and fish for such a role. Local contamination by
      some toxic metals is still a cause for concern in the St. Lawrence River.

PMID- 14570417
TI  - Water quality evaluation and trend analysis in selected watersheds of the
      Atlantic region of Canada.
AB  - Water quality indices (WQIs) have been developed to assess the suitability of
      water for a variety of uses. These indices reflect the status of water quality in
      lakes, streams, rivers, and reservoirs. The concept of WQIs is based on a
      comparison of the concentration of contaminants with the respective environmental
      standards. The number, frequency, and magnitude by which the environmental
      standards for specific variables are not met in a given time period are reflected
      in WQIs. Further, the water quality trend analysis predicts the behavior of the
      water quality parameters and overall water quality in the time domain. In this
      paper, the concept of WQI was applied to three selected watersheds of Atlantic
      region: the Mersey River, the Point Wolfe River, and the Dunk River sites. To
      have robust study, two different water quality indices are used: Canadian Water
      Quality Index (CWQI), and British Columbia Water Quality Index (BWQI). The
      complete study was conducted in two steps. The first step was to organize and
      process the data into a format compatible with WQI analysis. After processing the
      input data, the WQI was calculated. The second step outlined in the paper
      discusses detailed trend analysis using linear and quadratic models for all the
      three sites. As per the 25 years trend analysis, overall water quality for
      agriculture use observed an improving trend at all the three sites studied. Water
      quality for raw water used for drinking (prior to treatment) and aquatic uses has
      shown improving trend at Point Wolfe River. It is further observed that pH, SO4,
      and NO3 concentrations are improving at Dunk River, Mersey River, and Point Wolfe
      River sites. To ascertain the reliability and significance of the trend analysis,
      a detailed error analysis and parametric significance tests were also conducted.
      It was observed that for most of the sites and water uses quadratic trend models
      were a better fit than the linear models.

PMID- 14570418
TI  - How and why is aquatic quality changing at Nahanni National Park Reserve, NWT,
      Canada?
AB  - Nahanni National Park Reserve is located at southwestern NWT-Yukon border. One of
      the first UNESCO World Heritage sites, Nahanni lies within Taiga Cordillera and
      Taiga Shield Ecozones. Base and precious metal mining occurred upstream of
      Nahanni prior to park establishment. Nahanni waters, sediments, fish, and caribou
      have naturally elevated metals levels. Baseline water, sediment and fish tissue
      quality data were collected and analyzed throughout Nahanni during 1988-91 and
      1992-97. These two programs characterized how aquatic quality variables are
      naturally varying in space and time, affected by geology, stream flow,
      seasonality, and extreme meteorological and geological events. Possible
      anthropogenic causes of aquatic quality change were examined. Measured values
      were compared to existing Guidelines and site-specific objectives were
      established.

PMID- 14570419
TI  - Status and trends of Ontario's Sydenham River ecosystem in relation to aquatic
      species at risk.
AB  - The Sydenham River in southwestern Ontario is located in the Mixedwood Plains
      Ecozone, which supports the greatest diversity of flora and fauna in Canada. The
      river historically supported a rich aquatic community that included 80 fishes and
      34 species of freshwater mussels. Fourteen aquatic species native to the river (8
      fishes, 5 mussels and 1 turtle) have been designated as endangered, threatened,
      or of special concern by the Committee on the Status of Species at Risk in Canada
      (COSEWIC). A multi-agency Recovery Team was formed in 1999 to ensure the
      continued survival of these and other rare species in the river. The Sydenham
      River Recovery Team is the first in Canada to adopt an ecosystem approach to
      recovery planning for aquatic species. Information on land use patterns, water
      quality trends, the physical condition of the river, and the distributions of
      aquatic species at risk was synthesized to gain an understanding of the overall
      health of the river and its major anthropogenic stresses. Seven of the species at
      risk have declined in distribution or abundance, and three may be extirpated. The
      main threat to fishes and mussels is heavy loadings of sediment, nutrients, and
      possibly pesticides to the river via tile drainage and overland runoff from
      agricultural lands. A strategy that incorporates four overall approaches
      (management, stewardship, research and monitoring, and awareness and outreach)
      was developed to recover and protect this globally significant freshwater
      ecosystem.

PMID- 14570420
TI  - Canadian environmental effects monitoring: experiences with pulp and paper and
      metal mining regulatory programs.
AB  - In Canada, Environmental Effects Monitoring (EEM) programs exist within two
      regulations: the Pulp and Paper Effluent Regulations and the new Metal Mining
      Effluent Regulations under the Canadian Fisheries Act. EEM provides a biological,
      effects-based feedback loop to assess the effectiveness of technology-based
      regulations in protecting receiving environments. The promulgation of the Pulp
      and Paper Effluent Regulations, in 1992, represented a significant step forward
      in the Canadian regulatory approach by incorporating directly into a regulation a
      requirement to assess the effects of effluent discharges on receiving
      environments using proven scientific monitoring methodologies. Similarly, an
      assessment of the aquatic impacts of mines resulted in recommendations to amend
      the Metal Mining Effluent Regulations, recently promulgated in 2002, and includes
      an EEM program as a science-based feedback loop. As such, these regulations
      recognize the possibility that national, technology-based standards may not
      necessarily protect all receiving environments because of the diversity and
      variability of both discharges and receiving sites across the country. Since that
      time, EEM has improved its flexibility by considering both advances in science
      and the uniqueness of monitoring sites across Canada to allow the most
      appropriate and cost-effective monitoring approaches at each site while
      maintaining national consistency. This paper discusses the use of monitoring
      under two Canadian regulations to assess effects on aquatic ecosystems. As well,
      the National EEM approach to maintaining up-to-date scientific practices in a
      national regulatory program is discussed using examples.

PMID- 14570421
TI  - Recommendations for monitoring of polybrominated diphenyl ethers in the Canadian
      environment.
AB  - Polybrominated diphenyl ethers (PBDEs) have been reported in air, surface waters,
      suspended sediments, soil, sediment, fish, marine mammals, and bird eggs
      throughout Canada, from the St. Lawrence Estuary to the Strait of Georgia and the
      northernmost reaches of the Canadian Arctic. Canadian scientists have detected
      the presence of PBDEs in breast milk in every Canadian province. In fact, recent
      data on temporal trends strongly suggests that the concentrations of PBDEs are on
      the rise in the Canadian environment. These findings are similar to those
      reported in other nordic countries, and have prompted several countries to
      implement environmental monitoring programs. Among the key challenges currently
      facing Canada and other countries concerns how best to measure these chemicals in
      different matrices. In this paper, several analytical methods cited in the
      scientific literature for determining PBDE concentrations in different abiotic
      and biological matrices are reviewed. The critical criteria required for accurate
      determination of PBDEs in complex environmental matrices are discussed, including
      instrument sensitivity, reliability, potential interference's and the need for
      specialized instrumentation for the determination of compounds up to 975 Daltons.
      While a single analytical method that meets these and other criteria has not yet
      been perfected by scientists, GC/HRMS-based methods amenable to isotope dilution
      techniques warrant further refinement, and likely represent the best tools for
      future environmental monitoring programs.

PMID- 14570422
TI  - Monitoring the conservation of grassland habitats, Prairie Ecozone, Canada.
AB  - The Prairie Ecozone contains 5% of Canada's land area and represents 16% of the
      Great Plains of North America. Current estimates indicate that 25-30% of original
      Canadian grassland habitats remain, largely concentrated in southeastern Alberta
      and southwestern Saskatchewan with fragments distributed throughout southern
      Manitoba. The size, distribution and condition of native grasslands serve as
      valuable indicators of the ecological integrity and the sustainability of those
      landscape types. With so little native grasslands remaining, areas that conserve
      grasslands serve as core sites for indicators such as gaps in ecosystem and
      wildlife habitat protection, i.e. which ecosystems are well-represented, poorly
      represented or have no representation. Such gap analyses helps to determine where
      protection efforts need to be placed in the future. Overall, about 3.5% of the
      Prairie Ecozone of Canada is under some form of conservation area status. This
      paper reports, relative to the ecoregions and political jurisdictions of the
      Prairie Ecozone, on the amount and distribution of various types of conservation
      areas and native grasslands. Relationships between the occurrence of conservation
      areas and grasslands are presented. Implications for conservation area planning
      and management are discussed within regional, national and international
      contexts. The issue of which characteristics of conservation areas should be
      assessed and monitored to address conservation objectives for sustainability is
      also discussed.

PMID- 14570423
TI  - Using temporal coherence to determine the response to climate change in Boreal
      Shield lakes.
AB  - Climate change is expected to have important impacts on aquatic ecosystems. On
      the Boreal Shield, mean annual air temperatures are expected to increase 2 to 4
      degrees C over the next 50 years. An important challenge is to predict how
      changes in climate and climate variability will impact natural systems so that
      sustainable management policies can be implemented. To predict responses to
      complex ecosystem changes associated with climate change, we used long-term
      biotic databases to evaluate how important elements of the biota in Boreal Shield
      lakes have responded to past fluctuations in climate. Our long-term records span
      a two decade period where there have been unusually cold years and unusually warm
      years. We used coherence analyses to test for regionally operating controls on
      climate, water temperature, pH, and plankton richness and abundance in three
      regions across Ontario: the Experimental Lakes Area, Sudbury, and Dorset. Inter
      annual variation in air temperature was similar among regions, but there was a
      weak relationship among regions for precipitation. While air temperature was
      closely related to lake surface temperatures in each of the regions, there were
      weak relationships between lake surface temperature and richness or abundance of
      the plankton. However, inter-annual changes in lake chemistry (i.e., pH) were
      correlated with some biotic variables. In some lakes in Sudbury and Dorset, pH
      was dependent on extreme events. For example, El Nino related droughts resulted
      in acidification pulses in some lakes that influenced phytoplankton and
      zooplankton richness. These results suggest that there can be strong
      heterogeneity in lake ecosystem responses within and across regions.

PMID- 14570424
TI  - Sharing the geo-referenced results of climate change impact research.
AB  - The Prairie Adaptation Research Collaborative (PARC) has implemented an Internet
      Map Server (IMS) at the PARC web site (www.parc.ca) to 1) disseminate the geo
      referenced results of PARC sponsored research on climate change impacts and
      adaptation, and 2) address data, information and knowledge management within the
      PARC network of researchers and partners. PARC facilitates interdisciplinary
      research on adaptation to the impacts of climate change in the Canadian Prairie
      Provinces. The web site is intended as a platform for sharing information and
      encouraging discussion of climate change impacts and adaptation. The IMS enables
      scientists and stakeholders to apply simple climate change scenarios to geo
      referenced biophysical and social data, and dynamically create maps that display
      the geographic distribution of potential impacts of climate change. With a
      limited capacity for spatial analysis, most geo-processing and the climate impact
      modeling is done offline within a GIS environment. The IMS will serve the output
      from climate impact models, such that the model results can be customized by the
      web site user and be most readily applied to the planning and analysis of
      adaptation strategies.

PMID- 14570425
TI  - Linking ecological science to decision-making: delivering environmental
      monitoring information as societal feedback.
AB  - The paper describes the Ecological Monitoring and Assessment Network's (EMAN)
      operational and program response to certain challenges of environmental
      monitoring in Canada, in particular, efforts to improve the ability of the
      network to deliver relevant information to decision makers. In addition to its
      familiar roles, environmental monitoring should deliver feedback to society on
      environmental changes associated with development patterns, trends, processes and
      interventions. In order for such feedback to be effective, it must be relevant,
      timely, useful and accessible: all characteristics that are defined by the user,
      not the provider. Demand driven environmental monitoring is explored through
      EMAN's experiences with Canada's Biosphere Reserves, the NatureWatch Program and
      the Canadian Community Monitoring Network.

PMID- 14570426
TI  - Establishing the Canadian Community Monitoring Network.
AB  - Community-based ecosystem monitoring activities in Canada are increasing in
      response to a number of factors including: (i) the needs of decision-makers for
      timely information on local environmental changes; (ii) limited use of government
      monitoring data and information by decision makers: (iii) government cuts to
      monitoring programs; (iv) the increasingly recognized need to include
      stakeholders in planning and management processes; and (v) the desire of citizens
      to contribute to environmental protection. To date there has been no network
      coordination of community based monitoring in Canada. This paper reports on the
      establishment of the Canadian Community Monitoring Network by Environment
      Canada's Ecological Monitoring and Assessment Network Coordinating Office and the
      Canadian Nature Federation. Information on research prepared in support of
      network establishment is presented along with a discussion of the potential of
      the network.

PMID- 14570427
TI  - Plant phenology in western Canada: trends and links to the view from space.
AB  - One feature of climate change is the trends to earlier spring onset in many north
      temperate areas of the world. The timing of spring flowering and leafing of
      perennial plants is largely controlled by temperature accumulation; both
      temperature and phenological records illustrate changes in recent decades.
      Phenology studies date back over a century, with extensive databases existing for
      western Canada. Earlier spring flowering has been noted for many woody plants,
      with larger trends seen for species that develop at spring's start. Implications
      for ecosystems of trends to earlier spring arrival include changes in plant
      species composition, changes in timing and distribution of pests and disease, and
      potentially disrupted ecological interactions. While Alberta has extensive
      phenology databases (for species, years, and geographic coverage) for recent
      decades, these data cannot provide continuous ground coverage. There is great
      potential for phenological data to provide ground validation for satellite
      imagery interpretation, especially as new remote sensors are becoming available.
      Phenological networks are experiencing a resurgence of interest in Canada
      (www.plantwatch.ca) and globally, and linking these ground-based observations
      with the view from space will greatly enhance our capacity to track the biotic
      response to climate changes.

PMID- 14570428
TI  - Patterns and trends in Southern Ontario lake ice phenology.
AB  - An analysis is presented of 46 ice break up and 15 ice free season phenology data
      series obtained largely through volunteer monitoring efforts in Southern Ontario.
      Observations spanned the years 1853-2001. Available data included dates of ice
      formation and ice break up as well as the number of ice free days in a year. A
      high degree of temporal coherence in ice phenology between lakes was observed
      (137/365 pairwise correlations significant at P < 0.05). Significant monotonic
      trends towards earlier break up dates and longer ice free seasons were observed
      across the region both in the entire series and in the last thirty years of data.
      Trends in longer series may be associated with the end of the Little Ice Age. The
      significantly longer ice free seasons and earlier ice break up dates observed in
      the study area have important implications for lakes in other parts of Canada
      where climate change effects are predicted to be more extreme than in South
      Central Ontario.

PMID- 14570429
TI  - Opportunities for improved risk assessments of exotic species in Canada using
      bioclimatic modeling.
AB  - This paper briefly reviews the process of exotic pest risk assessments and
      presents some examples of emerging opportunities for spatial bioclimatic modeling
      of exotic species in Canada. This type of analysis can support risk assessments
      but does not replace the need for on-going high quality field-based observations
      to validate and update models. Bioclimatic analysis of several exotic pests is
      provided to illustrate both opportunities and limits. A link is demonstrated to
      the National Forest Inventory to characterize timber volumes at risk for one
      exotic species. 'Challenges' are both scientific and administrative. More
      accessible and current field survey data are required to improve models. Our
      experience is that for many exotic species, historical, and even current, data
      are not always digital or quality controlled for taxonomic identity and accurate
      geo-referencing. This inhibits their use for integrated spatial modeling
      applications.

PMID- 14570430
TI  - Introduction to underemployment and its social costs.

PMID- 14570431
TI  - Unemployment, underemployment, and mental health: conceptualizing employment
      status as a continuum.
AB  - The economy is one of the most important social environments that affect well
      being, and community psychologists have long studied the social costs of one key
      economic stressor--job loss. But economically inadequate employment has received
      much less research attention than unemployment in regard to mental health
      effects. This paper contrasts these two literatures and considers factors that
      might account for their differential growth including actual rates of
      unemployment and underemployment. Recent panel studies offer no support for
      another possible basis for this differential growth--the assumption that
      inadequate employment is more like adequate employment than unemployment.
      Implications of a paradigm shift from a dichotomous perspective (employment vs.
      unemployment) to a continuum perspective with variations of both unemployment and
      employment are discussed for research and prevention. Another implication is the
      need to expand standard labor force statistics to reflect better the degree of
      underemployment.

PMID- 14570432
TI  - Underemployment in America: measurement and evidence.
AB  - An important way in which employment hardship has come to be conceptualized and
      measured is as underemployment. Underemployment goes beyond mere unemployment
      (being out of a job and looking for work), to include those who have given up
      looking for work, part-time workers whose employer(s) cannot give them full-time
      work, and the working poor. To provide needed background for the other articles
      in this special issue, we trace the history of the concept of underemployment,
      review existing empirical literature, offer a critique of the measurement of
      underemployment as conventionally operationalized, and provide up-to-date
      evidence on the trends and correlates of underemployment in the United States.

PMID- 14570433
TI  - Underemployment: consequences for the health and well-being of workers.
AB  - This paper addresses the question of how the adequacy of a person's employment
      status influences their health. We draw on and extend the Labor Utilization
      Framework to distinguish between different forms of underemployment (hours,
      income, skills, and status) and test their relative effects on a range of
      physical health and psychological well-being outcomes. Using data drawn from a
      nationally representative sample (N = 1,429) of adults of working age, we assess
      the concurrent effects of underemployment through a longitudinal design that
      controls for prior levels of health and well-being. The results indicate that
      underemployed workers do report lower levels of health and well-being than
      adequately employed workers. However, the relationship varies by both types of
      underemployment and indicator of health and well-being. We conclude by discussing
      future research to explore the relationship between underemployment and health
      and well-being.

PMID- 14570434
TI  - Economic antecedents of foster care.
AB  - Individual and ecological research suggests that rising unemployment may affect
      the incidence of violence through two countervailing mechanisms suggested by
      frustration-aggression theory. The first, or provocation effect, assumes
      increased violence among persons who feel anger because they believe their job
      loss was arbitrary. The second, or inhibition effect, posits less violence among
      employed persons who attempt to reduce their chances of job loss by curtailing
      behavior objectionable to employers. The literature also reports that these
      mechanisms affect victimization measured as foster care sought by the state for
      abused children. The foster care finding, although consistent with theory and
      important for basic as well as applied reasons, arises from methods that cannot
      rule out several rival hypotheses. We revisit this research and apply improved
      methods to test the reported association in Los Angeles and San Francisco
      counties. We find that, as implied by the provocation and inhibition mechanisms,
      differences in monthly prevalence of foster care placements increase with modest
      increases in unemployment but decline when unemployment becomes much higher than
      usual levels.

PMID- 14570435
TI  - Human costs of organizational downsizing: comparing health trends between leavers
      and stayers.
AB  - We studied health-related selection and consequences of an organizational
      downsizing among 886 municipal employees. Measurements of health indicators were
      conducted before any rumor of the downsizing and immediately after the downsizing
      3 years later. Results of pre-downsizing health showed that those who did not
      find employment after the staff reductions were older employees with high
      preexisting morbidity. Those getting a new job elsewhere were younger and had
      better health already before the downsizing than the stayers. After the
      downsizing, deterioration of health was most likely in the stayers working in
      groups of major staff reductions and among the nonemployed leavers. In the
      reemployed leavers, the risk of increased health problems was lower than in
      others including employees working in no or minor downsizing groups.

PMID- 14570436
TI  - Long-term unemployment among young people: the risk of social exclusion.
AB  - The European Union considers long-term unemployment among youth an impediment to
      their full integration into society. The Commission of the European Union has,
      therefore, supported research into the mechanisms by which youth unemployment
      leads to "social exclusion." This paper provides a brief summary of the project's
      findings. These imply that theories and previous research concerning social
      exclusion and social support can help explain the effects of youth unemployment
      although the phenomena vary from country to country. Results also suggest that
      the construct of social exclusion leads to interventions that reduce the personal
      and societal costs of youth unemployment.

PMID- 14570437
TI  - Career centered high school education and post-high school career adaptation.
AB  - This study examines the quality of the transition into employment roles among a
      socioeconomically diverse cohort of 1,143 high school seniors who were
      interviewed as seniors in 1998 and 2 years later. Focusing on both subjective and
      objective dimensions of work adaptation, analyses examine differences in these
      outcomes associated with taking a high school career-major versus a more
      traditional academic program. This type of major is intended to assist in the
      career development and economic adaptation of more disadvantaged young adults and
      follows from an ecological model emphasizing the importance of connections
      between educational and employment institutions in the socialization of young
      people. Results indicate small but significant effects of having the career-major
      for the perceptual variables. Group differences were not found for the variables
      assessing more objective qualities of their jobs. The discrepancy between
      subjective and objective outcomes may suggest a short-term psychological optimism
      in the absence of an objective situation that would justify this view. Discussion
      centers on the need for stronger institutional support for school-work
      connections.

PMID- 14570438
TI  - Toward a critical community psychological perspective on unemployment and mental
      health research.
AB  - Psychological research has established that unemployment causes widespread
      psychological distress and ill health in communities but, arguably, little of
      this research is truly community psychological. In this paper we sketch out a
      critical community psychological perspective and use it to contribute to
      understanding of the role of psychosocial aspects of income in the experience and
      mental health of employed and unemployed members of low-income families in a
      severely deprived community context; to the development of innovative
      participatory methodology, and to promote the interests of impoverished
      unemployed people through the research process as well as through the research
      outcome.

PMID- 14570439
TI  - American psychology and schools: a critique.
AB  - No one denies that the Boulder Conference on Clinical Psychology marked a turning
      point on American psychology. This paper by one of the three or four living
      participants lists the conference as one in which psychology was at a choice
      point, went in one and only one direction, without examining the possible
      consequences or the possibility of going in more than 1 direction. A second theme
      is that the APA has to be faulted for a lack of searching self-scrutiny of its
      past. Organizations, like individuals, resist such self-scrutiny.

PMID- 14570440
TI  - Inner-city African American parental involvement in children's schooling: racial
      socialization and social support from the parent community.
AB  - Parents (n = 161) and teachers (n = 18) from an urban elementary school serving
      primarily African American children completed questionnaires regarding racial
      socialization, social support, and involvement in activities that support youth
      educational achievement at home and school. Parental reports of racism awareness,
      and contact with school staff were significantly correlated with parent reports
      of at-home involvement and at-school involvement. Parent reports of social
      support from the parent community were significantly related to at-home
      involvement only. Relative to teacher reports, parents reported more formal
      contacts with school staff, and higher levels of racism awareness, religiosity,
      and African American cultural pride. Teachers and parents agreed on school
      climate and parental levels of at-home and at-school involvement. The results
      suggest that racial socialization processes are related to parent involvement in
      children's schooling and that increased efforts are needed to bridge a cultural
      gap between parents and teachers in inner-city communities.

PMID- 14570441
TI  - Exploring violence exposure, stress, protective factors and behavioral problems
      among inner-city youth.
AB  - This study examined relationships between violence exposure, other stressors,
      family support, and self-concept on self-reported behavioral problems among 320
      urban adolescents (aged 11-18) referred for mental health treatment. Overall,
      participants reported high levels of violence exposure, with a median of six past
      encounters with violence as a witness, victim, or through the experiences of
      associates. All forms of violence exposure (witnessing, being a victim, knowing
      of victims) were correlated with internalizing and externalizing behavioral
      problems for males and females. Total violence exposure predicted behavioral
      problems among participants, even after controlling for the effects of other
      risk, demographic and protective factors. Family support and self-concept
      moderated the influence of life stress and cumulative risk on problem behavior
      outcomes, but these protective variables did not significantly moderate violence
      exposure.

PMID- 14570442
TI  - The interplay among risk factors for suicidal ideation and suicide: the role of
      depression, poor health, and loved ones' messages of support and criticism.
AB  - When individuals who receive social support are in poor physical or mental health
      and are criticized or made to feel unwanted, they may perceive themselves as a
      burden. Poor physical health and depression were hypothesized to exacerbate the
      harmful effects on suicidal ideation of receiving critical negative messages and
      of receiving social support. These hypotheses were tested using secondary
      analyses of data from a sample of 533 unemployed married individuals who were
      assessed shortly after job loss, and 6 months later. The results of our analyses
      supported the hypotheses and demonstrated that for participants with poor health
      or high level of depressive symptoms an increase in critical messages and social
      support (from Time 1 to Time 2) predicted increased suicidal ideation. This
      relationship was not observed for non-depressed participants in good health. The
      results are discussed in terms of their implications for suicide prevention.

PMID- 14570443
TI  - What front-line CBO staff can tell us about culturally anchored theories of
      behavior change in HIV prevention for Asian/Pacific Islanders.
AB  - Few rigorously tested primary prevention programs have been developed to prevent
      HIV infection among immigrant communities in the United States. This is in part
      because of the lack of culturally specific behavioral theories that can inform
      HIV prevention for immigrant communities in the United States. This article aims
      to develop such theories for a population--Asian/Pacific Islanders (A/PIs)
      immigrant communities--who have been overlooked in theory development and program
      evaluation. Frontline community-based organization (CBO) peer educators, an
      underutilized source of expertise regarding cultural factors specific to HIV
      infection among A/PI communities, are the sample of study Asian/Pacific Islander
      peer educators working at an urban AIDS service organization devoted to health
      promotion for this population; (N = 35). They were interviewed to examine (1)
      detailed narratives describing instances of behavior change and (2) culturally
      anchored theories of behavior change which the narratives imply. Theories of the
      influence of positive cultural symbols on the taboo of HIV/AIDS, moderators of
      the effectiveness of social network influences on behavior change, and setting-
      and community-level processes predicting HIV risk behavior were implicit in the
      peer educators' narratives. Implications for future research, methodology and
      prevention practice are discussed.

PMID- 14570444
TI  - Family, school, and community factors and relationships to racial-ethnic
      attitudes and academic achievement.
AB  - This study examined family, school, and community factors and the relationships
      to racial-ethnic attitudes and academic achievement among 98 African American
      fourth-grade children. It has been posited that young people who feel better
      about their racial-ethnic background have better behavioral and academic
      outcomes, yet there is a need for more empirical tests of this premise.
      Psychometric information is reported on measures of parent, teacher, and child
      racial-ethnic attitudes. Path analysis was used to investigate ecological
      variables potentially related to children's racial-ethnic attitudes and
      achievement. Parental education and level of racial-ethnic pride were correlated
      and both were related to children's achievement though in the final path model,
      only the path from parental education level was statistically significant.
      Children whose teachers exhibited higher levels of racial-ethnic trust and
      perceived fewer barriers due to race and ethnicity evidenced more trust and
      optimism as well. Children living in communities with higher proportions of
      college-educated residents also exhibited more positive racial-ethnic attitudes.
      For children, higher racial-ethnic pride was related to higher achievement
      measured by grades and standardized test scores, while racial distrust and
      perception of barriers due to race were related to reduced performance. This
      study suggests that family, school, and community are all important factors
      related to children's racial-ethnic attitudes and also to their academic
      achievement.

PMID- 14570445
TI  - The effects of family and neighborhood characteristics on the behavioral and
      cognitive development of poor Black children: a longitudinal study.
AB  - Using data from an ongoing study of 178 single-mother, Black families, this study
      investigates the relations among family resources (mothers' employment, income
      from employment, and educational attainment), maternal depressive symptoms,
      neighborhood quality in the preschool years and over time, and child
      developmental outcomes (behavior problems, broad reading, calculation) in the
      early school years. Results indicate that behavior problems in school-age
      children were associated with behavior problems early on, the child's gender, the
      mother's depressive symptoms and, to some extent, her employment status. However,
      these findings were conditioned by the mother's educational attainment and her
      evaluation of neighborhood problems early on. Better broad reading scores were
      associated with higher maternal educational attainment, especially for school-age
      girls of employed mothers, whereas higher calculation scores were predicted by
      fewer school-age behavior problems and, in the presence of higher neighborhood
      problems in the preschool years, mothers' higher educational attainment.

PMID- 14570446
TI  - Patterns of coping among persons with HIV infection: configurations, correlates,
      and change.
AB  - This study examines coping in response to HIV infection, using longitudinal data
      from a nationally representative sample (n = 2,864) of HIV-infected persons. We
      investigated configurations of coping responses, the correlates of configuration
      membership, the stability of coping configurations, and the relationship of
      coping to emotional well-being. Four coping configurations emerged from cluster
      analyses: relatively frequent use of blame-withdrawal coping, frequent use of
      distancing, frequent active-approach coping, and infrequent use of all three
      coping strategies ("passive" copers). Passive copers had few symptoms, high
      levels of physical functioning, and high emotional well-being; blame-withdrawal
      copers had the opposite pattern. Of those completing a second interview 1 year
      after baseline, 46% had the same coping configuration. Increases in the number of
      HIV-related symptoms raised the probability of blame-withdrawal coping at follow
      up, whereas decreases raised the probability of passive coping. Infrequent use of
      coping responses at baseline was related to greater emotional well-being 1 year
      later. This result, in conjunction with the high levels of emotional well-being
      in the passive cluster, suggests that high levels of distress can induce blame
      withdrawal coping whereas coping efforts are minimal when social support and
      emotional well-being are high. Results highlight issues in ascertaining the
      causal direction between coping and psychological outcomes, as well as in
      specifying the nature of stressful situations with which people are coping.

PMID- 14570447
TI  - Molding of three-dimensional microstructures of gels.
AB  - This Communication describes the use of patterned elastomeric stamps to mold,
      release, and stack hydrogels into three-dimensional microstructures. Molding of
      gels against stamps derivatized by a hexa(ethylene glycol)-terminated self
      assembled monolayer or by an adsorbed monolayer of bovine serum albumin allowed
      the application of several soft lithographic techniques (replica molding,
      microtransfer molding, and micromolding in capillaries) to the microfabrication
      of gels. We describe procedures to generate coplanar or bilayered composites of
      gels.

PMID- 14570448
TI  - Stereoselective iodocyclopropanation of terminal alkenes with iodoform,
      chromium(II) chloride, and N,N,N',N'-tetraethylethylenediamine.
AB  - Chemoselectivity of a reagent for (E)-olefination of aldehydes derived by
      reduction of iodoform with chromium(II) chloride in THF changes markedly by
      addition of TEEDA (N,N,N',N'-tetraethylethylenediamine), and trans
      iodocyclopropanes are produced stereoselectively from terminal alkenes by
      treatment with the base-added reagent system. The iodocyclopropanation occurs
      only at terminal double bonds, and di- and trisubstituted double bonds in the
      same molecules remained unchanged. Such functional groups as alcohol, ether,
      silyl ether, ester, tertiary amine, and amide groups are compatible with the
      reaction conditions.

PMID- 14570449
TI  - Radical polymerization initiated by Bergman cyclization.
AB  - The diradical generated by the Bergman cyclization of 3,4-benzocyclodec-3-ene-1,5
      diyne is shown to initiate the radical polymerization of several monomers.
      Methacrylates are polymerized to high molecular weight by the diradical initiator
      much more efficiently than other monomers. The relation between the rate of
      polymerization and the degree of polymerization indicates that the polymer
      primarily propagates as a monoradical. This monoradical growth is in agreement
      with established theory predicting that diradical initiators can produce high
      polymer only through chain transfer followed by monoradical growth due to the
      rapid intramolecular termination of short diradical chains. In agreement with
      this mechanism, the polymerization rate of acrylonitrile initiated by the
      diradical is shown to increase by more than 20-fold upon addition of a chain
      transfer agent. Small molecule products consistent with intramolecular
      termination of diradical oligomers were isolated, and the structures of these
      molecules suggest how the diradical self-terminates in the absence of chain
      transfer.

PMID- 14570450
TI  - Regioselective synthesis of unsymmetrical C-aryl glycosides using silicon tethers
      as disposable linkers.
AB  - Silicon tethers were employed to control the regiochemistry of Diels-Alder
      reactions between substituted benzynes and glycosyl furans as a key step in the
      syntheses of unsymmetrical representatives of three major groups of C-aryl
      glycosides. The cycloaddition precursors were readily prepared by O-alkylation of
      substituted phenols with various sugar-substituted furylsilane derivatives.
      Selective deprotonation on the benzene ring of these ethers led to a benzyne that
      underwent an intramolecular Diels-Alder reaction to give bridged cycloadducts.
      Fluoride-induced removal of the silicon tether and acid-catalyzed ring opening of
      the oxabicycloheptadiene subunit yielded the desired C-aryl glycosides as single
      isomers.

PMID- 14570451
TI  - Dioxygen-coupled oxidative amination of styrene.
AB  - Dioxygen-coupled oxidative amination of olefins is an attractive, but
      challenging, catalytic transformation. The present work describes the first
      general method for intermolecular oxidative amination of aryl olefins with
      molecular oxygen as the stoichiometric oxidant. This palladium-catalyzed
      reactivity is compatible with several different nitrogen nucleophiles, including
      oxazolidinone, phthalimide, pyrrolidinone, and p-toluenesulfonamide. The presence
      of a catalytic quantity of a Bronsted base in the reaction increases the
      catalytic activity and switches the reaction regioselectivity.

PMID- 14570452
TI  - Microbial synthesis of the energetic material precursor 1,2,4-butanetriol.
AB  - The lack of a route to precursor 1,2,4-butanetriol that is amenable to large
      scale synthesis has impeded substitution of 1,2,4-butanetriol trinitrate for
      nitroglycerin. To identify an alternative to the current commercial synthesis of
      racemic d,l-1,2,4-butanetriol involving NaBH4 reduction of esterified d,l-malic
      acid, microbial syntheses of d- and l-1,2,4-butanetriol have been established.
      These microbial syntheses rely on the creation of biosynthetic pathways that do
      not exist in nature. Oxidation of d-xylose by Pseudomonas fragi provides d
      xylonic acid in 70% yield. Escherichia coli DH5alpha/pWN6.186A then catalyzes the
      conversion of d-xylonic acid into d-1,2,4-butanetriol in 25% yield. P. fragi is
      also used to oxidize l-arabinose to a mixture of l-arabino-1,4-lactone and l
      arabinonic acid in 54% overall yield. After hydrolysis of the lactone, l
      arabinonic acid is converted to l-1,2,4-butanetriol in 35% yield using E. coli
      BL21(DE3)/pWN6.222A. As a catalytic route to 1,2,4-butanetriol, microbial
      synthesis avoids the high H2 pressures and elevated temperatures required by
      catalytic hydrogenation of malic acid.

PMID- 14570453
TI  - Catalyzed olefin isomerization leading to highly stereoselective Claisen
      rearrangements of aliphatic allyl vinyl ethers.
AB  - Iridium(I)-catalyzed olefin isomerization in bis(allyl) ethers is integrated into
      a generally applicable strategy for affecting highly stereoselective Claisen
      rearrangements. Catalyzed alkene isomerization affords allyl vinyl ethers from
      easily prepared di(allyl) ethers; direct thermolysis of these reaction mixtures
      leads to highly diastereoselective [3,3] sigmatropic rearrangements affording syn
      2,3-dialkyl-4-pentenal derivatives. An easily executed strategy for realizing
      asymmetric variants of the isomerization-Claisen rearrangement (ICR) reactions is
      also described.

PMID- 14570454
TI  - Indium-catalyzed addition of active methylene compounds to 1-alkynes.
AB  - An active methylene compound adds to a 1-alkyne in high to quantitative yield
      upon heating in the presence of 0.05-5 mol % of In(OTf)3 to give an alpha
      alkenylated carbonyl compound.

PMID- 14570455
TI  - Facile synthesis of a fullerene-barbituric acid derivative and supramolecular
      catalysis of its photoinduced dimerization.
AB  - A straightforward synthesis of a fullerene derivative appended with a barbituric
      acid molecular recognition motif is described. The presence of two nonself
      complementary hydrogen-bonding sites is shown to be conducive to the construction
      of supramolecular assemblies. In the presence of a melamine derivative possessing
      complementary hydrogen-bonding sites, enhanced efficiency toward
      photodimerization of the fullerene moiety is observed. This represents the first
      example of intermolecular photodimerization of a fullerene derivative in
      homogeneous solution, made possible by the formation of supramolecular assemblies
      in which the fullerenes are maintained in close proximity.

PMID- 14570456
TI  - Isolation, characterization, and reaction of activated iodosylbenzene monomer
      hydroxy(phenyl)iodonium ion with hypervalent bonding: supramolecular complex
      PhI+OH.18-crown-6 with secondary I...O interactions.
AB  - The isolation, characterization, and reaction of the active species
      hydroxy(phenyl)iodonium ion with hypervalent bonding are reported. Reaction of
      iodosylbenzene with HBF(4)-Me(2)O in the presence of equimolar 18-crown-6 in
      dichloromethane afforded the hydroxy-lambda(3)-iodane complex PhI(OH)BF(4).18
      crown-6 as stable yellow prisms. X-ray structure analysis indicated that both the
      close contacts between the iodine(III) and the three adjacent oxygen atoms of 18
      crown-6, and the hydrogen bonding OH.O(crown ether) will be responsible for the
      increased stability of the complex as compared to the uncomplexed PhI(OH)BF(4).
      The crown ether complex is highly reactive and serves as a versatile oxidant even
      in water: thus, the complex undergoes oxidative transformations of a variety of
      functional groups such as olefins, alkynes, enones, silyl enol ethers, sulfides,
      and phenols under mild conditions.

PMID- 14570457
TI  - Evidence for hydrogen abstraction from C1 of taurine by the high-spin Fe(IV)
      intermediate detected during oxygen activation by taurine:alpha-ketoglutarate
      dioxygenase (TauD).
AB  - The Fe(II)- and alpha-ketoglutarate-dependent dioxygenases catalyze hydroxylation
      reactions of considerable biomedical and environmental significance. Recently,
      the first oxidized iron intermediate in the reaction of a member of this family,
      taurine:alpha-ketoglutarate dioxygenase (TauD), was detected and shown to be a
      high-spin, formally Fe(IV) complex. The demonstration in this study that decay of
      the Fe(IV) complex is approximately 30-fold slower when it is formed in the
      presence of 1-[2H]2-taurine provides evidence that the intermediate abstracts
      hydrogen from C1, the site of hydroxylation, and suggests that quantum-mechanical
      tunneling may contribute to C1-H cleavage.

PMID- 14570458
TI  - Multinuclear oxo-bridged manganese complexes with a bulky substituted benzoate
      ligand: novel species obtained by using steric control.
AB  - A sterically hindered carboxylate ligand is used to synthesize the first
      transition metal complex containing both bis-mu-oxo and bis-mu-carboxylato
      groups, [Mn2(mu-O)2(mu-ArtolCO2)2(bpy)2]+. However, methyl substitution on the
      chelating bipyridine ligand results in the formation of a strikingly different
      and novel hexanuclear species, [Mn6(mu-O)4(mu3-O)4(mu-ArtolCO2)2(dmb)6]4+. Steric
      interactions between the bridging carboxylates and chelating pyridine-based
      ligands determine the nuclearity of the complexes formed.

PMID- 14570459
TI  - Asymmetric cyclization via memory of chirality: a concise access to cyclic amino
      acids with a quaternary stereocenter.
AB  - N-(omega-Bromoalkyl)-amino acid derivatives, readily prepared from natural alpha
      amino acids, gave cyclic amino acids with a quaternary stereocenter by treatment
      with potassium hexamethyldisilazaide in DMF. The chirality of parent amino acids
      was almost completely preserved during an enolate-formation and cyclization
      process, giving aza-cyclic amino acids in up to 98% ee in retention of
      configuration. This method is applicable to the asymmetric synthesis of
      azetidine, pyrrolidine, piperidine, and azepane derivatives. The asymmetric
      cyclization seems to proceed via an axially chiral enolate intermediate and not
      through a concerted SEi process.

PMID- 14570460
TI  - Electroless deposition of palladium at bare and templated liquid/liquid
      interfaces.
AB  - A simple, electroless approach to metallize the liquid/liquid interface is
      reported. The method is illustrated with the deposition of Pd at the bare
      water/1,2-dichloroethane interface, and for the "templated" deposition of Pd
      within the 100 nm diameter pores of gamma-alumina membranes.

PMID- 14570461
TI  - Supramolecular design for multivalent interaction: maltose mobility along
      polyrotaxane enhanced binding with concanavalin A.
AB  - High molecular mobility of maltose-conjugated alpha-cyclodextrins (alpha-CDs)
      along a poly(ethylene glycol) (PEG) chain due to the mechanically locked
      structure of polyrotaxanes enhanced multivalent interactions between maltose and
      concanavalin A (Con A). When maltose groups are conjugated with alpha-CDs that
      were threaded onto a PEG capped with benzyloxycarbonyl l-tyrosine (polyrotaxane),
      Con A-induced hemagglutination was greatly inhibited by polyrotaxanes with a
      certain threading % of alpha-CDs. Such an inhibitory effect was significantly
      superior to the other type of conjugates, in which poly(acrylic acid) was used as
      a backbone for maltose conjugation. The spin-spin relaxation time (T2) of the
      maltose C(1) proton in the polyrotaxane at a typical alpha-CD threading % was
      significantly larger than that of any other conjugate, which was well related to
      the inhibitory effect. Therefore, we concluded that the high mobility of maltose
      groups along the polyrotaxane structure contributes to enhanced Con A
      recognition.

PMID- 14570462
TI  - A new strategy to induce gamma-turns: peptides composed of alternating alpha
      aminoxy acids and alpha-amino acids.
AB  - It is known that the seven-membered-ring intramolecular hydrogen bond (gamma
      turn) is seldom formed in naturally occurring peptides composed of alpha-amino
      acids. Here we report a new strategy to induce gamma-turns in short linear
      peptides. We designed and synthesized several peptides (1-5) containing
      alternating alpha-l-aminoxy acids and alpha-d-amino acids. 1H NMR studies
      revealed that the gamma-turn could be initiated by the following N-O turn, an
      eight-membered-ring intramolecular hydrogen bond induced by an alpha-aminoxy
      acid. Moreover, NOESY and CD studies suggested peptides 4 and 5 form a novel
      secondary structure, a mixed 7-8 helix. Theoretical calculations on several di-,
      tri-, and tetrapeptide models provided strong support to the above conclusions.

PMID- 14570463
TI  - Metallabenzene versus Cp complex formation: a DFT investigation.
AB  - One common reaction that metallabenzene complexes undergo is the formation of
      cyclopentadienyl (Cp) complexes. Density functional theory (DFT) was used here to
      investigate the reaction mechanism. It was found that the reaction can proceed
      via a carbene migratory insertion class of C-C coupling. Cp complexes are found
      to be thermodynamically favored, except for the case of (C5H5Ir)(PH3)2Cl2 (1j)
      where the metallabenzene was favored. Isolation a rhodiabenzene of the type
      (C5H5Rh)(PH3)2Cl2 (1m) and a palladiabenzene, such as (C5H5Pd)Cp (1p), may be
      possible.

PMID- 14570464
TI  - A general strategy to elisabethane diterpenes: stereocontrolled synthesis of
      elisapterosin B via oxidative cyclization of an elisabethin precursor.
AB  - Described is an efficient synthesis of the complex bioactive natural product,
      elisapterosin B, a potent in vitro inhibitor of Mycobacterium tuberculosis H37Rb.
      The synthesis elisapterosin B, prepared in its enantiomeric form, proceeds by a
      highly stereocontrolled sequence commencing with a simple glutamic acid derived
      compound. Pivotal steps in the sequence include (a) a pinacol-type ketal
      rearrangement to transfer chirality, (b) an IMDA reaction of an E,Z-diene to
      construct the elisabethin skeleton, and (c) a biosynthesis-inspired oxidative
      cyclization of the elisabethin precursor to elisapterosin B.

PMID- 14570465
TI  - How does product isotope effect prove the operation of a two-state "rebound"
      mechanism in C-H hydroxylation by cytochrome P450?
AB  - C-H hydroxylation is a fundamental process. In Nature it is catalyzed by the
      enzyme cytochrome P450, in a still-debated mechanism that poses a major
      intellectual challenge for both experiment and theory; currently, the opinions
      keep swaying between the original single-state rebound mechanism, a two-oxidant
      mechanism (where ferric peroxide participates as a second oxidant, in addition to
      the primary active species, the high-valent iron-oxo species), and two-state
      reactivity (TSR) mechanism (where two spin states are involved). Recent product
      isotope effect (PIE) measurements for the trans-2-phenyl-methyl cyclopropane
      probe (1), led Newcomb and co-workers (Newcomb, M.; Aebisher, D.; Shen, R.;
      Esala, R.; Chandrasena, P.; Hollenberg, P.; Coon, M. J. J. Am. Chem. Soc. 2003,
      125, 6064-6065) to rule out TSR in favor of the two-oxidant scenario, since the
      direction of the PIE was at odds with the one predicted from calculations on
      methane hydroxylation. The present report describes a density functional
      theoretical study of C-H hydroxylation of the Newcomb probe, 1, leading to
      rearranged (3) and unrearranged (2) products. Our study shows that the reaction
      occurs via TSR in which the high-spin pathway gives dominant rearranged products,
      whereas the low-spin pathway favors unrearranged products. The calculated
      PIE(2/3) values based on TSR are found to be in excellent agreement with the
      experimental data of Newcomb and co-workers. This match between experiment and
      theory makes a strong case that the reaction occurs via TSR mechanism.

PMID- 14570467
TI  - Formation of the intermediate-spin iron(III) porphyrin complexes with (dxz,
      dyz)3(dxy)1(dz2)1 electron configuration.
AB  - On the basis of the difference in meso-13C chemical shifts, we have concluded
      that the intermediate-spin iron(III) complexes with highly ruffled and highly
      saddled porphyrins have different electron configurations. While the latter has a
      conventional (dxy)2(dxz, dyz)2(dz2)1, the former adopts a novel (dxz,
      dyz)3(dxy)1(dz2)1.

PMID- 14570466
TI  - Electrokinetic trapping and concentration enrichment of DNA in a microfluidic
      channel.
AB  - We report a simple and efficient method for enriching the concentration of
      charged analytes within microfluidic channels. The method relies on exerting
      spatial control over the electrokinetic velocity of an analyte. Specifically, the
      electroosmotic (eo) velocity of the buffer solution in one region of the
      microfluidic system opposes the electrophoretic (ep) velocity of the analyte in
      the other region. This results in ep transport of DNA to the location where the
      ep and eo velocities are equal and opposite. Accumulation of the analyte occurs
      at this location. This enrichment method is conceptually distinct from field
      amplification stacking, isotachophoresis, micelle sweeping, size exclusion, and
      other methods that have been previously reported. The method requires no complex
      microfabricated structures, no special manipulation of the solvent, and the
      enriched analyte remains in solution rather than being captured on a solid
      support. A concentration enrichment factor of 800 can be achieved for 20mer DNA
      in a fluidic channel having dimensions of 100 mum x 25 mum x 5 mm. The time
      required to achieve this level of enrichment is 300 s, and the enriched zone has
      a minimum width of 100 mum.

PMID- 14570468
TI  - Controllable diastereoselective cyclopropanation. Enantioselective synthesis of
      vinylcyclopropanes via chiral telluronium ylides.
AB  - Novel chiral telluronium salts 1 are designed for asymmetric synthesis of 1,3
      disubstituted 2-vinylcyclopropanes. The allylides, generated in situ from the
      corresponding telluronium salt in the presence of different base, reacted with
      alpha,beta-unsaturated esters, ketones, and amides to afford cis-2-silylvinyl
      trans-3-substituted or trans-2-silylvinyl-trans-3-substituted cyclopropane
      derivatives with high diastereoselectivity and excellent enantioselectivity in
      good to high yields. Thus, either one of the two diastereomers could be
      enantioselectively synthesized at will just by the choice of LiTMP/HMPA or
      LDA/LiBr. The first examples of catalytic ylide reaction for enantioselective
      synthesis of 1,3-disubstituted 2-vinylcyclopropanes with high distereoselectivity
      is also achieved.

PMID- 14570469
TI  - Remarkable effect of pore size on the catalytic activity of mesoporous silica for
      the acetalization of cyclohexanone with methanol.
AB  - The catalytic activity of mesoporous silica (MCM-41) for the acetalization of
      cyclohexanone shows a volcano-shaped dependence on the pore diameter. The
      diameter of the cyclohexanone molecule is ca. 0.75 nm, while its acetalization
      with methanol was well accelerated on MCM-41 with a pore diameter of
      approximately 1.9 nm, and smaller or larger pores were not suitable for the
      catalysis. The catalytic activity was independent of the Al concentration.

PMID- 14570470
TI  - Kinetic evaluation of phenolase activity of tyrosinase using simplified catalytic
      reaction system.
AB  - A very simple tyrosinase reaction system has been developed using borate anion as
      a trapping agent of catechols and hydroxylamine as an external reductant to
      evaluate the phenolase activity without the interference of catecholase activity.
      Reactivities of variously para-substituted phenols in this system were compared
      directly to those of the phenols in the model reactions, demonstrating that the
      enzymatic oxygenation reaction of phenols proceeds via the same mechanism as the
      model reaction, that is, electrophilic aromatic substitution mechanism.

PMID- 14570471
TI  - 34S isotope effect on sulfate ester hydrolysis: mechanistic implications.
AB  - In this communication, we report the first determination of 34S kinetic isotope
      effects (KIEs) for the hydrolysis of sulfate monoesters. The method involves the
      conversion of the inorganic sulfate, acquired at partial extent of reaction, to
      SO2, followed by isotope ratio determination by mass spectrometry. The KIEs
      determined for p-nitrophenyl sulfate and p-acetylphenyl sulfate are 1.0154 (+/
      0.0002) and 1.0172 (+/-0.0003), respectively. These results, together with
      previous peripheral 18O KIE values, are inconsistent with an associative
      mechanism. The isotope effect method we report should also prove useful for
      studying the mechanism of other sulfuryl group transfers, including sulfatase and
      sulfotransferase reactions, as well as sulfate hydrolyses under other conditions.

PMID- 14570472
TI  - Identification of surface molecular hydrates on solid sulfuric acid films.
AB  - Infrared spectroscopic and secondary ion mass spectrometric studies reveal the
      presence of a stable molecular hydrate on the surface of condensed thin films of
      ionic sulfuric acid hydrates. This surface species is observed to play a role in
      the interaction of ammonia, reacting rapidly until the material is depleted. A
      slower, continuous process is also observed, attributed to a diffusion-limited
      reaction between incoming NH3 and H3O+ located at or near the surface.

PMID- 14570474
TI  - Indium-mediated reaction of trialkylsilyl propargyl bromide with aldehydes:
      highly regioselective synthesis of allenic and homopropargylic alcohols.
AB  - High regioselective preparation of either the allenic alcohols or homopropargylic
      alcohols using the indium-mediated reaction of trialkylsilyl propargyl bromides
      with various aldehydes has been accomplished. By just changing the silyl groups
      and the reaction conditions, both the allenic and homopropargylic alcohols can be
      obtained in high regioselectivities.

PMID- 14570473
TI  - Selective association of cholesterol with long-chain phospholipids in liquid
      ordered bilayers: support for the existence of lipid rafts.
AB  - Nearest-neighbor recognition experiments, which have been carried out under
      fluidizing and condensing conditions, using exchangeable dimers derived from 1,2
      dimyristoyl-sn-glycero-3-phosphoethanolamine, 1,2-distearoyl-sn-glycero-3
      phosphoethanolamine, and cholesterol, have provided strong evidence that sterol
      phospholipid recognition is limited to the liquid-ordered phase.

PMID- 14570475
TI  - Ten-electron coordination and reactivity of an arylphosphinidene ligand.
AB  - Photochemical decarbonylation of [Mo2Cp2(mu-PR*)(CO)4] (Cp = eta5-C5H5; R* =
      2,4,6-C6H2tBu3) gives [Mo2Cp2(mu-kappa1:kappa1,eta6-PR*)(CO)2], which shows the
      first example of a remarkable 10-electron donor arylphosphinidene ligand which
      bridges two Mo atoms through its phosphorus atom while being pi-bonded to one Mo
      center through the six carbon atoms of the aryl ring. This causes a severe
      pyramidal distortion of the P-bound C atom. The complex adds CO to give
      [Mo2Cp2(mu-kappa1:kappa1,eta4-PR*)(CO)3], which has an 8-electron donor PR*
      ligand, and then the parent complex [Mo2Cp2(mu-PR*)(CO)4]. Protonation of
      [Mo2Cp2(mu-kappa1:kappa1,eta6-PR*)(CO)2] gives the hydride [Mo2Cp2(H)(mu
      kappa1:kappa1,eta6-PR*)(CO)2]+, which undergoes P-C bond cleavage and hydride
      migration, affording the phosphido cation [Mo2Cp2(mu-P)(eta6-R*H)(CO)2]+.

PMID- 14570476
TI  - Sequential and specific exchange of multiple coiled-coil components.
AB  - The capacity for sequential and specific exchange of single peptides from coiled
      coil heterotrimers is investigated. Dual hydrophobic-hydrophilic interface
      systems permit iterative cycles of pH-triggered strand exchange that can
      specifically replace one, two, or even all three initial trimer components. The
      resultant new complexes are either resistant to or capable of further exchange.
      Control experiments demonstrate that background exchange among different
      complexes is negligible. When triggered, however, selective displacement of the
      same peptide from only one of two distinct heterotrimers is feasible. Previously
      documented peptidic cross-linking strategies remain operative in these more
      intricate environments.

PMID- 14570477
TI  - Design of amino acid sulfonamides as transition-state analogue inhibitors of
      arginase.
AB  - Arginase is a binuclear manganese metalloenzyme that catalyzes the hydrolysis of
      L-arginine to form L-ornithine plus urea. Chiral L-amino acids bearing
      sulfonamide side chains have been synthesized in which the tetrahedral
      sulfonamide groups are designed to target bridging coordination interactions with
      the binuclear manganese cluster in the arginase active site. Syntheses of the
      amino acid sulfonamides have been accomplished by the amination of sulfonyl
      halide derivatives of (S)-(tert-butoxy)-[(tert-butoxycarbonyl)amino]oxoalkanoic
      acids. Amino acid sulfonamides with side chains comparable in length to that of L
      arginine exhibit inhibition in the micromolar range, and the X-ray crystal
      structure of arginase I complexed with one of these inhibitors, S-(2
      sulfonamidoethyl)-L-cysteine, has been determined at 2.8 A resolution. In the
      enzyme-inhibitor complex, the sulfonamide group displaces the metal-bridging
      hydroxide ion of the native enzyme and bridges the binuclear manganese cluster
      with an ionized NH(-) group. The binding mode of the sulfonamide inhibitor may
      mimic the binding of the tetrahedral intermediate and its flanking transition
      states in catalysis. It is notable that the ionized sulfonamide group is an
      excellent bridging ligand in this enzyme-inhibitor complex; accordingly, the
      sulfonamide functionality can be considered in the design of inhibitors targeting
      other binuclear metalloenzymes.

PMID- 14570478
TI  - Large-scale millisecond intersubunit dynamics in the B subunit homopentamer of
      the toxin derived from Escherichia coli O157.
AB  - We report here solution NMR relaxation measurements that show millisecond time
      scale intersubunit dynamics in the homopentameric B subunit (VTB) of the toxin
      derived from Escherichia coli O157. These data are consistent with
      interconversion between an axially symmetric form and a low-abundance (
      approximately 10%, 45 degrees C) higher energy form. The higher energy state is
      depopulated on binding of a novel bivalent analogue (P(k) dimer) of the natural
      carbohydrate acceptor globotriaosylceramide. The isothermal titration calorimetry
      isotherm for the binding of P(k) dimer to VTB is consistent with a five-site
      sequential binding model which assumes that cooperative effects arise through
      communication only between neighboring binding sites. The resulting thermodynamic
      parameters (K(a1) = 114 +/- 2.2 M(-1), K(a2) = 283 +/- 4.5 M(-1), DeltaH(1)
      degrees = -116.3 +/- 0.55 kJ/mol, and DeltaH(2) degrees = -50.3 +/- 0.11 kJ/mol)
      indicate favorable entropic cooperativity that has not previously been observed
      in multivalent systems.

PMID- 14570479
TI  - Optical spectra of synechocystis and spinach photosystem II preparations at 1.7
      K: identification of the D1-pheophytin energies and stark shifts.
AB  - We report and compare highly resolved, simultaneously recorded absorption and CD
      spectra of active Photosystem II (PSII) samples in the range 440-750 nm. From an
      appropriately scaled comparison of spinach membrane fragment (BBY) and PSII core
      spectra, we show that key features of the core spectrum are quantitatively
      represented in the BBY data. PSII from the cyanobacterium Synechocystis 6803
      display spectral features in the Qy region of comparable width (50-70 cm(-1)
      fwhm) to those seen in plant PSII but the energies of the resolved features are
      distinctly different. A comparison of spectra taken of PSII poised in the S1QA
      and S2QA(-) redox states reveals electrochromic shifts largely attributable to
      the influence of QA(-) on Pheo(D1). This allows accurate determinations of the
      Pheo(D1) Qy absorption positions to be at 685.0 nm for spinach cores, 685.8 nm
      for BBY particles, and 683.0 nm for Synechocystis. These are discussed in terms
      of earlier reports of the Pheo(D1) energies in PSII. The Qx transition of
      Pheo(D1) undergoes a blue shift upon Q(A) reduction, and we place a lower limit
      of 80 cm(-1) on this shift in plant material. By comparing the magnitude of the
      Stark shifts of the Qx and Qy bands of Pheo(D1), the directions of the transition
      induced dipole moment changes, Deltamu(x) and Deltamu(y), for this functionally
      important pigment could be determined, assuming normal magnitudes of the
      Deltamu's. Consequently, Deltamu(x) and Deltamu(y) are determined to be
      approximately orthogonal to the directions expected for these transitions. Low
      fluence illumination experiments at 1.7 K resulted in very efficient formation of
      QA(-). This was accompanied by cyt b(559) oxidation in BBYs and carotenoid
      oxidation in cores. No chlorophyll oxidation was observed. Our data allow us to
      estimate the quantum efficiency of PSII at this temperature to be of the order
      0.1-1. No Stark shift associated with the S1-to-S2 transition of the Mn cluster
      is evident in our samples. The similarity of Stark data in plants and
      Synechocystis points to minimal interactions of Pheo(D1) with nearby chloropyll
      pigments in active PSII preparations. This appears to be at variance with
      interpretations of experiments performed with inactive solubilized reaction
      center preparations.

PMID- 14570480
TI  - Direct detection of a hydrogen ligand in the [NiFe] center of the regulatory H2
      sensing hydrogenase from Ralstonia eutropha in its reduced state by HYSCORE and
      ENDOR spectroscopy.
AB  - The regulatory H2-sensing [NiFe] hydrogenase of the beta-proteobacterium
      Ralstonia eutropha displays an Ni-C "active" state after reduction with H2 that
      is very similar to the reduced Ni-C state of standard [NiFe] hydrogenases. Pulse
      electron nuclear double resonance (ENDOR) and four-pulse ESEEM (hyperfine
      sublevel correlation, HYSCORE) spectroscopy are applied to obtain structural
      information on this state via detection of the electron-nuclear hyperfine
      coupling constants. Two proton hyperfine couplings are determined by analysis of
      ENDOR spectra recorded over the full magnetic field range of the EPR spectrum.
      These are associated with nonexchangeable protons and belong to the beta-CH(2)
      protons of a bridging cysteine of the NiFe center. The signals of a third proton
      exhibit a large anisotropic coupling (Ax = 18.4 MHz, Ay = -10.8 MHz, Az = -18
      MHz). They disappear from the 1H region of the ENDOR spectra after exchange of
      H2O with 2H2O and activation with 2H2 instead of H2 gas. They reappear in the 2H
      region of the ENDOR and HYSCORE spectra. Based on a comparison with the
      spectroscopically similar [NiFe] hydrogenase of Desulfovibrio vulgaris Miyazaki
      F, for which the g-tensor orientation of the Ni-C state with respect to the
      crystal structure is known (Foerster et al. J. Am. Chem. Soc. 2003, 125, 83-93),
      an assignment of the 1H hyperfine couplings is proposed. The exchangeable proton
      resides in a bridging position between the Ni and Fe and is assigned to a formal
      hydride ion. After illumination at low temperature (T = 10 K), the Ni-L state is
      formed. For the Ni-L state, the strong hyperfine coupling observed for the
      exchangeable hydrogen in Ni-C is lost, indicating a cleavage of the metal-hydride
      bond(s). These experiments give first direct information on the position of
      hydrogen binding in the active NiFe center of the regulatory hydrogenase. It is
      proposed that such a binding situation is also present in the active Ni-C state
      of standard hydrogenases.

PMID- 14570481
TI  - The plumber's nightmare: a new morphology in block copolymer-ceramic
      nanocomposites and mesoporous aluminosilicates.
AB  - A novel cubic bicontinuous morphology is found in polymer-ceramic nanocomposites
      and mesoporous aluminosilicates that are derived by an amphiphilic diblock
      copolymer, poly(isoprene-b-ethylene oxide) (PI-b-PEO), used as a structure
      directing agent for an inorganic aluminosilicate. Small-angle X-ray scattering
      (SAXS) was employed to unambiguously identify the Im(-)3m crystallographic
      symmetry of the materials by fitting individual Bragg peak positions in the two
      dimensional X-ray images. Structure factor calculations, in conjunction with
      results from transmission electron microscopy, were used to narrow the range of
      possible structures consistent with the symmetry and showed the plumber's
      nightmare morphology to be consistent with the data. The samples are made by
      deposition onto a substrate that imposes a strain field, generating a lattice
      distortion. This distortion is quantitatively analyzed and shown to have resulted
      in shrinkage of the crystallites by approximately one-third in a direction
      perpendicular to the substrate, in both as-made composites and calcined ceramic
      materials. Finally, the observation of the bicontinuous block-copolymer-derived
      hybrid morphology is discussed in the context of a pseudo-ternary morphology
      diagram and compared to existing studies of ternary phase diagrams of amphiphiles
      in a mixture of two solvents. The calcined mesoporous materials have potential
      applications in the fields of catalysis, separation technology, and
      microelectronics.

PMID- 14570482
TI  - Biosynthesis of vitamin B1 in yeast. Derivation of the pyrimidine unit from
      pyridoxine and histidine. Intermediacy of urocanic acid.
AB  - Incorporation studies with 13C-, 15N-, and 2H-labeled substrates, followed by NMR
      analysis, show that the pyrimidine unit of thiamin (Vitamin B1) originates from a
      C5N fragment, derived from C-2',2,N,C-6,5,5' of pyridoxol (Vitamin B6) and an N-C
      N fragment derived from L-histidine. Urocanic acid serves as an intermediate on
      the route of the N-C-N fragment of histidine into the thiamin pyrimidine.

PMID- 14570483
TI  - Transition state differences in hydrolysis reactions of alkyl versus aryl
      phosphate monoester monoanions.
AB  - Although aryl phosphates have been the subject of numerous experimental studies,
      far less data bearing on the mechanism and transition states for alkyl phosphate
      reactions have been presented. Except for esters with very good leaving groups
      such as 2,4-dinitrophenol, the monoanion of phosphate esters is more reactive
      than the dianion. Several mechanisms have been proposed for the hydrolysis of the
      monoanion species. (18)O kinetic isotope effects in the nonbridging oxygen atoms
      and in the P-O(R) ester bond, and solvent deuterium isotope effects, have been
      measured for the hydrolysis of m-nitrobenzyl phosphate. The results rule out a
      proposed mechanism in which the phosphoryl group deprotonates water and then
      undergoes attack by hydroxide. The results are most consistent with a
      preequilibrium proton transfer from the phosphoryl group to the ester oxygen
      atom, followed by rate-limiting P-O bond fission, as originally proposed by Kirby
      and co-workers in 1967. The transition state for m-nitrobenzyl phosphate (leaving
      group pK(a) 14.9) exhibits much less P-O bond fission than the reaction of the
      more labile p-nitrophenyl phosphate (leaving group pK(a) = 7.14). This seemingly
      anti-Hammond behavior results from weakening of the P-O(R) ester bond resulting
      from protonation, an effect which calculations have shown is much more pronounced
      for aryl phosphates than for alkyl ones.

PMID- 14570484
TI  - 2,3-anhydrosugars in glycoside bond synthesis. NMR and computational
      investigations into the mechanism of glycosylations with 2,3-anhydrofuranosyl
      glycosyl sulfoxides.
AB  - We report here the combined use of computational chemistry and low-temperature
      NMR spectroscopy to probe the mechanism of a highly stereoselective glycosylation
      reaction employing 2,3-anhydrofuranosyl glycosyl sulfoxides (2 and 4). The
      reaction involves a two-step process that is carried out in one pot. In the first
      step, the sulfoxide is reacted with triflic anhydride leading to the formation of
      a single intermediate. Using NMR spectroscopy, we have established the structure
      of this intermediate as a glycosyl triflate. In the second step, the acceptor
      alcohol is added to the reaction mixture, which leads to the highly
      stereocontrolled formation of the glycoside product. The structure of the major
      product is consistent with a pathway involving an S(N)2-like displacement of the
      triflate by the alcohol. In the predominant intermediate that is formed, there is
      a trans relationship between the triflate group and epoxide. Therefore, in the
      glycoside product there is a cis relationship between the epoxide and the
      aglycone. In addition to providing insight into these reaction pathways, these
      investigations have also allowed us to identify conditions under which the
      glycosylations can be made to proceed with even greater stereoselectivity and in
      higher yield.

PMID- 14570485
TI  - Direct determination of the number of electrons needed to reduce coenzyme F430
      pentamethyl ester to the Ni(I) species exhibiting the electron paramagnetic
      resonance and ultraviolet-visible spectra characteristic for the MCR(red1) state
      of methyl-coenzyme M reductase.
AB  - The UV-visible and electron paramagnetic resonance (EPR) spectra of MCR(red1),
      the catalytically active state of methyl-coenzyme M reductase, are almost
      identical to those observed when free coenzyme F430 or its pentamethyl ester
      (F430M) are reduced to the Ni(I) valence state. Investigations and proposals
      concerning the catalytic mechanism of MCR were therefore based on MCR(red1)
      containing Ni(I)F430 until, in a recent report, Tang et al. (J. Am. Chem. Soc.
      2002, 124, 13242) interpreted their resonance Raman data and titration
      experiments as indicating that, in MCR(red1), coenzyme F430 is not only reduced
      at the nickel center but at one of the C=N double bonds of the hydrocorphinoid
      macrocycle as well. To resolve this contradiction, we have investigated the
      stoichiometry of the reduction of coenzyme F430 pentamethyl ester (F430M) by
      three independent methods. Spectroelectrochemistry showed clean reduction to a
      single product that exhibits the UV-vis spectrum typical for MCR(red1). In three
      bulk electrolysis experiments, 0.96 +/- 0.1 F/mol was required to generate the
      reduced species. Reduction with decamethylcobaltocene in tetrahydrofuran (THF)
      consumed 1 mol of (Cp)(2)Co/mol of F430M, and the stoichiometry of the
      reoxidation of the reduced form with the two-electron oxidant methylene blue was
      0.46 +/- 0.05 mol of methylene blue/mol of reduced F430M. These experiments
      demonstrate that the reduction of coenzyme F430M to the species having almost
      identical UV-vis and EPR spectra as MCR(red1) is a one-electron process and
      therefore inconsistent with a reduction of the macrocycle chromophore.

PMID- 14570486
TI  - Hydroformylation reactions with recyclable rhodium-complexed dendrimers on a
      resin.
AB  - Rhodium-complexed dendrimers supported on a resin were evaluated as catalysts for
      the hydroformylation of aryl olefins and vinyl esters. The results showed the
      reactions proceeded very efficiently at room temperature with excellent yields.
      Outstanding selectivity for the branched aldehydes was also observed in all
      cases. The dendritic catalysts can be recycled by simple filtration and reused
      even up to the tenth cycle without loss of activity and selectivity. These
      results represent a dramatic improvement over those previously described for
      rhodium-catalyzed (dendrimer and nondendrimer based) hydroformylation reactions.

PMID- 14570487
TI  - Structure assignment, total synthesis, and antiviral evaluation of cycloviracin
      B1.
AB  - The first total synthesis of the antivirally active glycolipid cycloviracin B(1)
      (1) is described. The approach is based on a two-directional synthesis strategy
      which constructs the C(2)()-symmetrical macrodiolide core of the target by an
      efficient template-directed macrodilactonization reaction promoted by 2-chloro
      1,3-dimethylimidazolinium chloride 14 as the activating agent. Attachment of the
      lateral fatty acid chains to the lactide core thus formed features not only one
      of the most advanced ligand-controlled addition reactions of a functionalized
      dialkyl zinc reagent to a polyfunctional aldehyde, but also a highly demanding
      Julia-Kocienski olefination of a tetrazolyl sulfone bearing electrophilic and
      base-labile beta-hydroxy ester motifs. By virtue of the flexibility of this
      synthesis plan, it was possible to prepare a series of macrodiolide cores
      differing only in the absolute stereochemistry at the branching points as well as
      a host of model compounds for the fatty acid appendices of cycloviracin.
      Comparison of these derivatives with the natural product allowed us to establish
      the as yet unknown absolute stereochemistry of 6 chiral centers of 1 as
      (3R,19S,25R,3'R,17'S,23'R). Thereby, the (13)C NMR shifts of the anomeric
      position of the beta-glycosides residing at those positions turned out to be
      excellent probes for the absolute configuration of the attached aglycones. The
      concise set of data thus obtained also makes clear that the proposed structure of
      the fattiviracins, a seemingly closely related family of glycoconjugates, is not
      matched by the published data. Finally, the biological activity of synthetic 1
      and some of the key intermediates obtained en route to this natural product was
      investigated, showing that the entire construct is necessary for appreciable and
      selective antiviral activity.

PMID- 14570488
TI  - New concepts in thermoplastic elastomers: the case of syndiotactic polypropylene,
      an unconventional elastomer with high crystallinity and large modulus.
AB  - Syndiotactic polypropylene (sPP), despite high crystallinity, shows unusual
      elastic properties, associated with a reversible crystal-crystal phase
      transition. The mechanism behind the crystal-crystal phase transition involved
      during cyclic elongation and recovery and the time scale of this process is here
      investigated, to unravel the origin of the elasticity of such an unconventional
      elastomer. The structural transformation of fibers of sPP during deformation has
      been studied by wide-angle X-ray diffraction measurements, using the high flux
      available on the beamline ID11 at the European Syncrotron Radiation Facility
      (ESRF), Grenoble, France, performing a time-resolved analysis of structural
      changes occurring while cyclically stretching and relaxing sPP fibers. This
      analysis indicates that the stress-induced phase transition is a martensitic
      transformation. As in martensitic phase transitions it occurs readily and
      directly, supporting the idea that elasticity in sPP is partially of enthalpic
      nature.

PMID- 14570489
TI  - Highly cooperative formation of bis-urea based supramolecular polymers.
AB  - Eleven bis-ureas have been synthesized, and some of their properties are
      reported. Several of these compounds form supramolecular polymers in organic
      solvents. The self-association is shown by FTIR spectroscopy to display
      cooperativity at two levels. The first level of cooperativity is due to the
      synergistic association of the two urea functions of a single molecule. The
      second level of cooperativity is revealed by the fact that the formation of
      dimers is less favored than that of long oligomers.

PMID- 14570490
TI  - Total syntheses of furaquinocin A, B, and E.
AB  - A modular approach to the total synthesis of furaquinocins culminated in the
      total syntheses of furaquinocin A, B, and E. A Pd-catalyzed dynamic kinetic
      asymmetric transformation (DYKAT) on carbonates derived from Baylis-Hillman
      adducts, followed by a reductive Heck cyclization allows the enantio- and
      diastereoselective construction of dihydrobenzofuran 32. Introduction of a double
      unsatured side chain via Horner-Wadsworth-Emmons reaction and assembly of the
      naphthoquinone with squaric acid based methodology leads to furaquinocin E. The
      use of differentially substituted squaric acid derivatives allows the synthesis
      of three analogues of furaquinocin E. The additional stereocenters in
      furaquinocin A and B can be introduced with a diastereoselective Sakurai
      allylation. The stereoselective elongation of the side chain is possible using
      cross metathesis or ring closing metathesis. The obtained late-stage
      intermediates were successfully transformed to furaquinocin A and B.

PMID- 14570491
TI  - Simultaneous light emission from a mixture of dendrimer encapsulated
      chromophores: a model for single-layer multichromophoric organic light-emitting
      diodes.
AB  - The site isolation of two dyes capable of electronic interaction via Forster
      energy transfer has been studied with the two dyes coumarin 343 and
      pentathiophene encapsulated by dendrons containing both solubilizing and
      electroactive moieties. Photoluminescence studies of mixtures of the dendritic
      dyes show that at high dendron generation, significant site isolation is achieved
      with relative emission characteristics influenced by both the degree of site
      isolation and the emission quantum yield of the dyes. Electroluminescence studies
      carried out in organic light emitting diode devices confirm that color tuning may
      be achieved by mixing the two encapsulated dyes in a single layer. However,
      selective carrier trapping by one of the core component dyes can dramatically
      influence the effectiveness of other components in the device.

PMID- 14570492
TI  - Controlling solubility and modulating peripheral function in dendrimer
      encapsulated dyes.
AB  - The synthesis of large dendrons and dendrimers with site-isolated dyes at their
      core has been explored. The dyes selected for this work were coumarin 343 and
      pentathiophene, as energy transfer processes prevail when the two dyes are
      intimately mixed but each should behave independently of the other if site
      isolation is achieved. Because the two dyes have very different functional
      characteristics, a protocol involving orthogonal protecting groups and allowing
      the use of a single family of electroactive dendrons for their encapsulation had
      to be developed. The synthetic protocol must balance the need to incorporate
      electroactive groups at the periphery of the dendrons with the requirement for
      high solubility and a size sufficient to fully encapsulate the central dye.
      Because of their poor solubility and tendency to crystallize, dendrons with
      uniform triarylamine substitution proved unsatisfactory leading to the
      development of new unsymmetrical dendrons with alternating branched alkyl groups
      and triarylamine moieties at their periphery. These dendrons, which show
      excellent solubility and no tendency to crystallize, were assembled into large
      dendrimers using a modular protocol with the light emitting dye at their core. It
      is expected that the large size of the dendritic shell will provide effective
      site-isolation for the encapsulated central dyes enabling them to exhibit their
      intrinsic emission properties with minimal energy transfer between neighboring
      core fluorophores when processed in bulk thin films.

PMID- 14570493
TI  - Homolytic vs heterolytic paths in the photochemistry of haloanilines.
AB  - The photochemistry of 4-haloanilines and 4-halo-N,N-dimethylanilines has been
      studied in apolar, polar aprotic, and protic solvents. Photophysical and flash
      photolysis experiments show that the reaction proceeds in any case from the
      triplet state. It is rather unreactive in apolar media, the highest value being
      Phi = 0.05 for the iodoanilines in cyclohexane. Changing the solvent has little
      effect for iodoanilines and for the poorly reacting bromo analogue, while it
      leads to a variation of over 2 orders of magnitude in the quantum yield for the
      chloro and fluoro derivatives. The triplets have been characterized at the
      UB3LYP/6-31G(d) level of theory, evidencing a deformation and an elongation
      (except for C-F) of the C-X bond. Homolytic fragmentation is in every case
      endothermic, but calculations in acetonitrile solution show that heterolytic
      cleavage of C-Cl and C-Br is exothermic. Experimentally, the occurrence of
      heterolytic fragmentation has been monitored through selective trapping of the
      resulting phenyl cation by allyltrimethylsilane. Heterolytic dechlorination
      occurs efficiently in polar media (e.g., Phi = 0.77 in MeCN), while debromination
      remains ineffective due to the short lifetime of the triplet. Heterolytic
      defluorination is efficient only in protic solvents (Phi = 0.48 in MeOH), in
      accord with calculations showing that in the presence of an ancillary molecule of
      water fragmentation is exothermic due to the formation of the strong H-F bond.
      The energy profile for both homo- and heterolytic dissociation paths has been
      mapped along the reaction coordinates in the gas phase and in acetonitrile. The
      conditions determining the efficiency and mode of dehalogenation have been
      defined. This is significant for devising synthetic methods via photogenerated
      phenyl cations and for rationalizing the photodegradation of halogenated aromatic
      pollutants and the phototoxic effect of some fluorinated drugs.

PMID- 14570494
TI  - Dramatic steric behavior in electron transfer from various donors to CF3Br.
AB  - Different alkali metal atoms are observed to donate electrons to CF(3)Br
      molecules that are oriented in space. For collision energies high enough to
      overcome the Coulomb attraction, a positive ion/negative ion pair is observed and
      mass-analyzed using coincident time-of-flight mass spectroscopy. The alkali metal
      cation and various negative ions are observed. The most abundant negative ion is
      the bromide ion, Br(-), formed preferentially by attack at the Br end of the
      molecule. The steric asymmetry to produce Br(-) is almost identical for all of
      the alkali metal donors. Fluoride ions are formed in smaller abundance and
      reflect completely different behavior among the donors. Sodium and potassium have
      high thresholds and prefer the CF(3) end of the molecule, whereas cesium prefers
      the Br end of the molecule. Sodium and potassium apparently interact with the
      transient CF(3)Br(-) molecular negative ion while it is in the process of
      decomposing.

PMID- 14570495
TI  - Direct observation of triplet state emission of single molecules: single molecule
      phosphorescence quenching of metalloporphyrin and organometallic complexes by
      molecular oxygen and their quenching rate distributions.
AB  - Single molecules are detected through the phosphorescence emission of their
      triplet states. Emission of the triplet states of single molecules of Pt
      octabutoxycarbonyl porphyrin (PtOBCP) and ruthenium(II)-tris-4,7-diphenyl-1,10
      phenanthroline dichloride (Ru(dpp)(3)Cl(2)) is reported. The single molecule
      phosphorescence is very sensitive to molecular oxygen. Each molecule has its own
      characteristic quenching rate by oxygen, and the distribution of these rates is
      measured for (Ru(dpp)(3)Cl(2)) on a quartz surface. The large variance of this
      distribution is presumed to be caused by fluctuations in the pseudobimolecular
      rate coefficient and the local oxygen concentration. The possibility of creating
      a quantitative single oxygen molecule sensor is suggested.

PMID- 14570496
TI  - Magnetic quantum dots: synthesis, spectroscopy, and magnetism of Co2+ - and Ni2+
      doped ZnO nanocrystals.
AB  - We report a method for the preparation of colloidal ZnO-diluted magnetic
      semiconductor quantum dots (DMS-QDs) by alkaline-activated hydrolysis and
      condensation of zinc acetate solutions in dimethyl sulfoxide (DMSO). Mechanistic
      studies reveal that Co(2+) and Ni(2+) dopants inhibit nucleation and growth of
      ZnO nanocrystals. In particular, dopants are quantitatively excluded from the
      critical nuclei but are incorporated nearly isotropically during subsequent
      growth of the nanocrystals. The smaller nanocrystal diameters that result upon
      doping are explained by the Gibbs-Thompson relationship between lattice strain
      and crystal solubility. We describe methods for cleaning the nanocrystal surfaces
      of exposed dopants and for redispersion of the final DMS-QDs. Homogeneous
      substitutional doping is verified by high-resolution low-temperature electronic
      absorption and magnetic circular dichroism (MCD) spectroscopies. A "giant Zeeman
      effect" is observed in the band gap transition of Co(2+):ZnO DMS-QDs. MCD and
      Zeeman spectroscopies are used to quantify the magnitude of the p-d exchange
      interaction (N(0)beta) that gives rise to this effect. N(0)beta values of -2.3 +/
      0.3 eV (-18 500 cm(-1)) for Co(2+):ZnO and -4.5 +/- 0.6 eV (-36 300 cm(-1)) for
      Ni(2+):ZnO have been determined. Ligand-to-metal charge-transfer transitions are
      observed in the MCD spectra of both Co(2+):ZnO and Ni(2+):ZnO DMS-QDs and are
      analyzed in the context of an optical electronegativity model. The importance of
      these charge-transfer states in determining N(0)beta is discussed. Ferromagnetism
      with T(C) > 350 K is observed in aggregated nanocrystals of Co(2+):ZnO that
      unambiguously demonstrates the existence of intrinsic high-T(C) ferromagnetism in
      this class of DMSs.

PMID- 14570497
TI  - Experimental evidence for a temperature dependent transition between normal and
      inverse equilibrium isotope effects for oxidative addition of H2 to
      Ir(PMe2Ph)2(CO)Cl.
AB  - The equilibrium isotope effect (EIE) for oxidative addition of H(2) and D(2) to
      Ir(PMe(2)Ph)(2)(CO)Cl has been measured over a large temperature range, thereby
      demonstrating that the inverse (<1) EIE previously observed at ambient
      temperature becomes normal (>1) at high temperature (>90 degrees C). The
      temperature dependence of the EIE for oxidative addition of H(2) and D(2) to
      Ir(PH(3))(2)(CO)Cl has been calculated using the geometry and vibrational
      frequencies obtained from DFT (B3LYP) calculations on Ir(PH(3))(2)(CO)ClH(2) and
      Ir(PH(3))(2)(CO)ClD(2), and is in accord with the experimentally observed
      transition from an inverse to normal EIE for oxidative addition of H(2) and D(2)
      to Ir(PMe(2)Ph)(2)(CO)Cl: the EIE is calculated to be inverse between 0 and 510
      K, reach a maximum value of 1.15 at 867 K and then slowly decrease to unity as
      the temperature approaches infinity. This deviation from simple van't Hoff
      behavior, and the occurrence of a maximum in the EIE, is the result of the
      entropy term being temperature dependent. At low temperature, the enthalpy term
      dominates and the EIE is inverse, whereas at high temperatures the entropy term
      dominates and the EIE is normal. The observation of both normal and inverse EIEs
      for the same system indicate that inferences pertaining to the magnitude of an
      isotope effect at a single temperature may require more detailed consideration
      than previously realized.

PMID- 14570498
TI  - Absorption and emission spectra of Ce3+ in elpasolite lattices.
AB  - The experimental determination of the electronic energy levels for Ce(3+) in some
      chloroelpasolite hosts for both the ground 4f(1) and the excited 5d(1)
      configurations is described. High-resolution f-f absorption and f-(2)T(2g) d
      absorption and emission spectra have been recorded at low temperatures for Ce(3+)
      diluted into various hexachloroelpasolite lattices. A fluorescence spectrum at
      approximately 50 000 cm(-1) is tentatively assigned to the emission from the
      highest 5d crystal field level, (2)E(g), of a Ce(3+) impurity in Cs(2)NaErCl(6),
      enabling the values of all the energy levels of both the 4f(1) and 5d(1)
      configurations to be given for Ce(3+) in elpasolite hosts. Vibronic structure
      superimposed on the electronic transitions is analyzed in terms of a simple
      configurational coordinate model involving the ground and excited configurations.
      It is found that the difference in the Ce-Cl bond length between the 4f(1) and
      5d(1) configurations is approximately 0.04 A. Ab initio model potential
      calculations on the (CeCl(6))(3-) cluster embedded in a reliable representation
      of the Cs(2)NaYCl(6) host support these conclusions.

PMID- 14570499
TI  - Monomeric MnIII/II and FeIII/II complexes with terminal hydroxo and oxo ligands:
      probing reactivity via O-H bond dissociation energies.
AB  - Non-heme manganese and iron complexes with terminal hydroxo or oxo ligands are
      proposed to mediate the transfer of hydrogen atoms in metalloproteins. To
      investigate this process in synthetic systems, the monomeric complexes
      [M(III/II)H(3)1(OH)](-/2-) and [M(III)H(3)1(O)](2-) have been prepared, where
      M(III/II) = Mn and Fe and [H(3)1](3-) is the tripodal ligand, tris[(N'-tert
      butylureaylato)-N-ethyl)]aminato. These complexes have similar primary and
      secondary coordination spheres, which are enforced by [H(3)1](3-). The homolytic
      bond dissociation energies (BDEs(O-H)) for the M(III/II)-OH complexes were
      determined, using experimentally obtained values for the pK(a)(M-OH) and E(1/2)
      measured in DMSO. This thermodynamic analysis gave BDEs(O-H) of 77(4) kcal/mol
      for [Mn(II)H(3)1(O-H)](2-) and 66(4) kcal/mol for [Fe(II)H(3)1(O-H)](2-). For the
      M(III)-OH complexes, [Mn(III)H(3)1(OH)]- and [Fe(III)H(3)1(OH)]-, BDEs(O-H) of
      110(4) and 115(4) kcal/mol were obtained. These BDEs(O-H) were verified with
      reactivity studies with substrates having known X-H bond energies (X = C, N, O).
      For instance, [Fe(II)H(3)1(OH)](2-) reacts with a TEMPO radical to afford
      [Fe(III)H(3)1(O)](2-) and TEMPO-H in isolated yields of 60 and 75%, respectively.
      Consistent with the BDE(O-H) values for [Mn(II)H(3)1(OH)](2-), TEMPO does not
      react with this complex, yet TEMPO-H (BDE(O-H) = 70 kcal/mol) reacts with
      [Mn(III)H(3)1(O)](2-), forming TEMPO and [Mn(II)H(3)1(OH)](2-).
      [Mn(III)H(3)1(O)](2-) and [Fe(III)H(3)1(O)](2-) react with other organic
      substrates containing C-H bonds less than 80 kcal/mol, including 9,10
      dihydroanthracene and 1,4-cyclohexadiene to produce [M(II)H(3)1(OH)](2-) and the
      appropriate dehydrogenated product in yields of greater than 80%. Treating
      [Mn(III)H(3)1(O)](2-) and [Fe(III)H(3)1(O)](2-) with phenolic compounds does not
      yield the product expected from hydrogen atom transfer but rather the protonated
      complexes, [Mn(III)H(3)1(OH)]- and [Fe(III)H(3)1(OH)]-, which is ascribed to the
      highly basic nature of the terminal oxo group.

PMID- 14570500
TI  - Asymmetric synthesis of unsaturated, fused bicyclic proline analogues through
      amino alkylation of cyclic bis(allylsulfoximine)titanium complexes and migratory
      cyclization of delta-amino alkenyl aminosulfoxonium salts.
AB  - Described is an asymmetric synthesis of new Delta(3a,4)-unsaturated, fused
      bicyclic proline analogues from cyclic bis(allylsulfoximine)titanium complexes
      and N-tert-butylsulfonyl imino ethyl ester. Treatment of the enantiomerically
      pure five-, six-, seven-, and eight-membered cyclic bis(allylsulfoximine)titanium
      complexes with the imino ester gave mixtures of the corresponding (E,syn)- and
      (Z,syn)-configured, delta-sulfoximine substituted, cyclic gamma,delta-unsaturated
      alpha-amino acid esters with high regio- and diastereoselectivities in good
      yields. Activation of the N-methyl sulfoximine group of these amino acid
      derivatives through methylation with Me(3)OBF(4) afforded in nearly quantitative
      yields the corresponding (dimethylamino)sulfoxonium salts. A novel migratory
      cyclization of these salts with DBU gave via an isomerization to the
      corresponding allylic (dimethylamino)sulfoxonium salts and an intramolecular
      substitution of the (dimethylamino)sulfoxonium group the enantio- and
      diastereomerically pure, bicyclic, N-tert-butylsulfonyl protected proline
      analogues having a six- and eight-membered unsaturated carbocyclic ring.
      Cyclization of the alkenyl (dimethylamino)sulfoxonium salts was independent of
      the configuration of the double bond. N,N-Dimethylphenylsulfinamide of > or =99%
      ee was obtained in good yield as a further reaction product. Conversion of the
      sulfinamide to N,S-dimethyl-S-phenylsulfoximine of > or =99% ee, the starting
      material for the synthesis of the allylic sulfoximines, had been accomplished
      previously. Finally, cleavage of the tert-butylsulfonyl protecting group with
      anhydrous acid furnished the fused bicyclic proline analogue containing an
      unsaturated six-membered ring in high yield.

PMID- 14570501
TI  - Insight into the partial oxidation of propene: the reactions of 2-propen-1-ol on
      clean and O-covered Mo(110).
AB  - The reactions of 2-propen-1-ol (allyl alcohol) were studied on clean and O
      covered Mo(110) to understand the effect of resonance stabilization and the
      presence of surface oxygen on reaction selectivity. Propene is the only gaseous
      hydrocarbon product evolved from allyl alcohol reaction on O-covered Mo(110).
      Water and dihydrogen are also produced, along with a small amount of adsorbed
      carbon. We estimated, using X-ray photoelectron spectroscopy, that approximately
      70% of the 0.11 ML of 2-propen-1-ol that reacts forms propene. In contrast, the
      dominant reaction pathway on the clean surface is nonselective decomposition to
      adsorbed carbon and hydrogen, leading to a 23% selectivity for propene formation.
      On both clean and O-covered Mo(110), X-ray photoelectron spectroscopy and
      infrared spectroscopy identify allyloxy as the reaction intermediate yielding
      propene. These results are discussed in the context of propene oxidation and
      periodic trends in reactivity.

PMID- 14570502
TI  - Stereoselective preparation of dienyl zirconocene complexes via a tandem allylic
      C-H bond activation-elimination sequence.
AB  - Several dienyl zirconocene derivatives were easily prepared, as unique
      geometrical isomers, from simple non-conjugated unsaturated enol ethers with (1
      butene)ZrCp2 complexes. This new methodology is based on a tandem allylic C-H
      bond activation-elimination sequence and the mechanism has been mapped out by
      deuterium labeling experiments. The stereochemical outcome of this process was
      determined by addition of several electrophiles. Moreover, when the
      organometallic derivative is vinylic as well as allylic such as in 44-47Zr, an
      unexpected reversal of the stereochemistry has been found during the zirconium to
      copper transmetalation step.

PMID- 14570503
TI  - Theoretical studies on the hydrolysis of mono-phosphate and tri-phosphate in gas
      phase and aqueous solution.
AB  - Phosphate hydrolysis by GTPases plays an important role as a molecular switch in
      signal transduction and as an initiator of many other biological processes.
      Despite the centrality of this ubiquitous reaction, the mechanism is still poorly
      understood. As a first step to understand the mechanisms of this process, the
      nonenzymatic hydrolysis of mono-phosphate and tri-phosphate esters were
      systematically studied in gas phase and aqueous solution using hybrid density
      functional methods. The dielectric effect of the environment on the energetics of
      these processes was also explored. Theoretical results show that for mono
      phosphate ester, the dissociative pathway is much more favorable than the
      associative pathway. However, the reaction barriers for the dissociative and
      associative pathways of tri-phosphate hydrolysis are very close in aqueous
      solution, though the dissociative pathway is more favorable in the gas phase.
      High dielectric solvents, such as water, significantly lower the activation
      barrier of the associative pathway due to the greater solvation energy of the
      associative transition states than that of the reactant complex. By contrast, the
      barrier of the dissociative pathway, with respect to the gas phase, is less
      sensitive to the surrounding dielectric. In the associative hydrolysis pathway of
      the tri-phosphate ester, negative charge is transferred from the gamma-phosphate
      to beta-phosphate through the bridging ester oxygen and results in Pgamma-O bond
      dissociation. No analogous charge transfer was observed in the dissociative
      pathway, where Pgamma-O bond dissociation resulted from proton transfer from the
      gamma-phosphate to the bridge oxygen. Finally, the active participation of local
      water molecules can significantly lower the activation energy of the dissociative
      pathway for both mono-phosphate and tri-phosphate.

PMID- 14570504
TI  - A seemingly well understood light-induced peroxide decarboxylation reaction
      reinvestigated with femtosecond time resolution.
AB  - The photoinduced (266 nm) ultrafast decarboxylation of the peroxyester tert-butyl
      9-methylfluorene-9-percarboxylate (TBFC) in solution has been studied with
      femtosecond time resolution. While the photodissociation of TBFC occurs too fast
      to be resolved, the intermediate 9-methylfluorenylcarbonyloxy radical (MeFl
      CO(2)) decarboxylates on a picosecond time scale. The latter process is monitored
      by pump-probe absorption spectroscopy at wavelengths between 400 and 883 nm. The
      measured transient absorbance signals reveal a dominant fast decay with a
      lifetime of a few picoseconds and, to a minor extent, a slow component with a
      lifetime of about 55 ps. Statistical modeling of MeFl-CO(2) decarboxylation
      employing molecular parameters calculated by density functional theory suggests
      that the fast component is associated with the decarboxylation of vibrationally
      hot radicals, whereas the 55 ps decay reflects the dissociation of thermally
      equilibrated MeFl-CO(2) at ambient temperature. The vast majority of MeFl-CO(2)
      radicals thus decarboxylate on a time scale about an order of magnitude faster
      than expected from the time constant of 55 ps reported by Falvey and Schuster for
      this reference reaction. This literature value turns out to refer to
      decarboxylation rate of MeFl-CO(2) at ambient temperature.

PMID- 14570505
TI  - NanoCell electronic memories.
AB  - NanoCells are disordered arrays of metallic islands that are interlinked with
      molecules between micrometer-sized metallic input/output leads. In the past,
      simulations had been conducted showing that the NanoCells may function as both
      memory and logic devices that are programmable postfabrication. Reported here is
      the first assembly of a NanoCell with disordered arrays of molecules and Au
      islands. The assembled NanoCells exhibit reproducible switching behavior and two
      types of memory effects at room temperature. The switch-type memory is
      characteristic of a destructive read, while the conductivity-type memory features
      a nondestructive read. Both types of memory effects are stable for more than a
      week at room temperature, and bit level ratios (0:1) of the conductivity-type
      memory have been observed to be as high as 10(4):1 and reaching 10(6):1 upon
      ozone treatment, which likely destroys extraneous leakage pathways. Both
      molecular electronic and nanofilamentary metal switching mechanisms have been
      considered, though the evidence points more strongly toward the latter. The
      approach here demonstrates the efficacy of a disordered nanoscale array for high
      yielding switching and memory while mitigating the arduous task of nanoscale
      patterning.

PMID- 14570506
TI  - Supramolecular assembly of dendritic polymers elucidated by 1H and 13C solid
      state MAS NMR spectroscopy.
AB  - Advanced solid-state NMR methods under fast magic-angle spinning (MAS) are used
      to study the structure and dynamics of large supramolecular systems, which
      consist of a polymer backbone with dendritic side groups and self-assemble into a
      columnar structure. The NMR experiments are performed on as-synthesized samples,
      i.e., no isotopic enrichment is required. The analysis of (1)H NMR chemical-shift
      effects as well as dipolar (1)H-(1)H or (1)H-(13)C couplings provide site
      specific insight into the local structure and the segmental dynamics, in
      particular, of phenyl rings and -CH(2)O- linking units within the dendrons.
      Relative changes of (1)H chemical shifts (of up to -3 ppm) serve as distance
      constraints and allow protons to be positioned relative to aromatic rings.
      Together with dipolar spinning sideband patterns, pi-pi packing phenomena and
      local order parameters (showing variations between 30% and 100%) are selectively
      and precisely determined, enabling the identification of the dendron cores as the
      structure-directing moieties within the supramolecular architecture. The study is
      carried out over a representative selection of systems which reflect
      characteristic differences, such as different polymer backbones, sizes of
      dendritic side groups, or length and flexibility of linking units. While the
      polymer backbone is found to have virtually no effect on the overall structure
      and properties, the systems are sensitively affected by changing the generation
      or the linkage of the dendrons. The results help to understand the self-assembly
      process of dendritic moieties and aid the chemical design of self-organizing
      molecular structures.

PMID- 14570507
TI  - In situ NMR spectroscopy of combustion.
AB  - The first successful in situ studies of free combustion processes by one- and two
      dimensional NMR spectroscopy are reported, and the feasibility of this concept is
      demonstrated. In this proof-of-principle work, methane combustion over a
      nanoporous material is investigated using hyperpolarized (hp)-xenon-129 NMR
      spectroscopy. Different inhomogeneous regions within the combustion cell are
      identified by the xenon chemical shift, and the gas exchange between these
      regions during combustion is revealed by two-dimensional exchange spectra (EXSY).
      The development of NMR spectroscopy as an analytical tool for combustion
      processes is of potential importance for catalyzed reactions within opaque media
      that are difficult to investigate by other techniques.

PMID- 14570509
TI  - Forgetting of intentions in demanding situations is rapid.
AB  - Demanding work settings often require the deferral of intended actions. In 3
      experiments, participants were to withhold a response until they encountered a
      task change (which occurred 5, 15, or 40 sec later). To approximate highly
      demanding settings, the experimenters sometimes divided attention during the
      delay period. During some of the delays the experimenters interrupted the
      participants with an additional task (Experiment 1). Demanding conditions as well
      as interruptions revealed rapid forgetting of intentions at levels that would be
      considered significant in applied settings. Experiments 2 and 3 showed that this
      rapid forgetting was not reduced by strategic rehearsal and implementation
      intention strategies. The results suggest that maintaining intentions over brief
      delays is not a trivial task for the human cognitive system.

PMID- 14570510
TI  - Eye movements and hazard perception in police pursuit and emergency response
      driving.
AB  - How do police cope with the visual demands placed on them during pursuit driving?
      This study compared the hazard ratings, eye movements, and physiological
      responses of police drivers with novice and with age-matched control drivers
      while viewing video clips of driving taken from police vehicles. The clips
      included pursuits, emergency responses, and control drives. Although police
      drivers did not report more hazards than the other participants reported, they
      had an increased frequency of electrodermal responses while viewing dangerous
      clips and a greater visual sampling rate and spread of search. However, despite
      an overall police advantage in oculomotor and physiological measures, all drivers
      had a reduced spread of search in nighttime pursuits because of the focusing of
      overt attention.

PMID- 14570511
TI  - Haptically creating affordances: the user-tool interface.
AB  - Successful use of a hand-held tool requires overcoming the rotational inertia of
      the hand-plus-tool system. Where an object is grasped affects this rotational
      inertia. Appropriate choice of grip position may be crucial in the safe,
      effective, and efficient control of a hand-held tool. In 3 experiments, the
      authors investigated how choice of grip position on a tool was constrained by
      task demands. The results suggest that choice of grasp position serves to
      establish relationships among 3 variables derived from the inertial ellipsoid of
      the hand-object system (volume, symmetry, and eigenvector angle) in a way that
      specifically reflected the power or precision constraints of the given task.
      These variables have previously been shown to play a role in haptic perception of
      tool function. Changing grasp position on a tool is a way to exert control over
      the nuances of the user-tool interface.

PMID- 14570512
TI  - I don't think that's what really happened: the effect of cross-examination on the
      accuracy of children's reports.
AB  - In the courtroom, child witnesses must undergo cross-examination. Prior research
      has shown that children change their original testimony under cross-examination,
      but the effect of these changes on the accuracy of children's testimony is
      unknown. The authors examined the effect of cross-examination on the accuracy of
      5- and 6-year-old children's (N=46) reports of a contrived event. Consistent with
      prior research, children made changes to their original responses during cross
      examination. Furthermore, these changes occurred irrespective of original
      accuracy. Finally, prior exposure to misleading information did not affect
      children's responses to cross-examination. Even children with no prior exposure
      to misinformation altered their original responses, decreasing their ultimate
      levels of accuracy. These findings demonstrate that cross-examination style
      questioning is inappropriate for young children.

PMID- 14570513
TI  - Judging the urgency of nonvocal auditory warning signals: perceptual and
      cognitive processes.
AB  - Previous research has identified acoustic properties modulating the perceived
      urgency of alarms. The authors conducted 3 experiments using a multidimensional
      approach in which participants made acoustic dissimilarity judgments and urgency
      dissimilarity judgments for pairs of sequences. Experiment 1 confirmed the
      validity of acoustic parameters in urgency perception of experimental alarms.
      Experiment 2 confirmed the role of these acoustic parameters with real alarms but
      suggested the importance of additional factors. Experiment 3 compared the
      relative degrees of urgency of alarms from Experiments 1 and 2, highlighting the
      role of both sequence structure and associated mental representation. The authors
      conclude that the design of alarms should not be based exclusively on acoustic
      factors but should also take into consideration the acquisition of an appropriate
      mental representation.

PMID- 14570514
TI  - More rapid associative change with retraining than with initial training.
AB  - Retraining was compared with initial acquisition in 4 magazine approach
      experiments with rats and 1 autoshaping experiment with pigeons. The levels of
      performance were matched prior to reinforcement and nonreinforcement for stimuli
      with a history of both training and extinction and stimuli with only a minimal
      history of training. Under these conditions, a previously extinguished stimulus
      was more vulnerable both to the incremental effects of reinforcement and to the
      decremental effects of nonreinforcement compared with a stimulus that had only
      been minimally trained.

PMID- 14570515
TI  - Pigeons use item-specific and category-level information in the identification
      and categorization of human faces.
AB  - Three experiments examined the pigeon's ability to adapt to the specific tasks of
      identification and categorization of complex visual stimuli by attending to
      information at different levels of abstraction. In Experiment 1, pigeons were
      successively trained to discriminate first between pairs of human faces from the
      same sex and then between male and female faces. A final test revealed that the
      associations formed in the first training phase did not survive categorization
      training, indicating that the pigeons used item-specific information to
      discriminate faces of the same sex, but shifted their attention to category-level
      information for discriminating between the male and female categories. Two
      further experiments disproved alternative explanations. The results support the
      feature-learning account of open-ended categorization in animals.

PMID- 14570516
TI  - Multiple-interval timing in rats: Performance on two-valued mixed fixed-interval
      schedules.
AB  - Three experiments studied timing in rats on 2-valued mixed-fixed-interval
      schedules, with equally probable components, Fixed-Interval S and Fixed-Interval
      L (FI S and FI L, respectively). When the L:S ratio was greater than 4, 2
      distinct response peaks appeared close to FI S and FI L, and data could be well
      fitted by the sum of 2 Gaussian curves. When the L:S ratio was less than 4, only
      1 response peak was usually visible, but nonlinear regression often identified
      separate sources of behavioral control, by FI S and FI L, although control by FI
      L dominated. Data were used to test ideas derived from scalar expectancy theory,
      the behavioral theory of timing, and learning to time.

PMID- 14570517
TI  - Context change as the mechanism of reinstatement in causal learning.
AB  - Four experiments were conducted to explore the mechanism of reinstatement in
      human causal learning. After a retroactive interference treatment in which a
      stimulus was first followed by an outcome (A+) and then followed by a different
      outcome (A*), simple exposure to the original outcome (+) in the interference
      test context produced partial reinstatement of the first-learned information
      (A+). When exposure to the outcome took place in a context different from the
      interference-test context, reinstatement was not observed (Experiment 1).
      Equivalent results appeared when the outcome presented during reinstatement was
      different from the one originally related to the stimulus affected by
      interference, independent of whether the interfering outcome (Experiments 2, 3,
      and 4) or a new outcome (Experiments 3 and 4) was presented before the test.
      These results suggest an interpretation of reinstatement in terms of a context
      change between interference and testing.

PMID- 14570518
TI  - Proactive interference between cues trained with a common outcome in first-order
      Pavlovian conditioning.
AB  - The nature of interference between cues (X, A) trained apart with a common
      outcome (O; an unconditioned stimulus) was explored by assessing proactive
      interference in first-order Pavlovian conditioning (i.e., A-O, X-O, resulting in
      attenuated responding to X). Three lick-suppression studies were conducted with
      water-deprived rats. Posttraining extinction of the interfering cue (A)
      attenuated proactive interference (Experiment 1), which mirrors the observation
      that extinction of the competing cue can reduce competition between cues trained
      together (e.g., recovery from overshadowing). Proactive interference was also
      attenuated with manipulations known to attenuate interference between outcomes
      trained apart (e.g., counterconditioning), namely reminder cues (Experiment 2)
      and renewal (Experiment 3). The findings suggest that similar processes underlie
      interference between cues trained apart, between cues trained together, and
      between outcomes trained apart.

PMID- 14570519
TI  - Temporally massed CS presentations generate more fear extinction than spaced
      presentations.
AB  - Rodent fear conditioning models both excitatory learning and the pathogenesis of
      human anxiety, whereas extinction of conditional fear is a paradigm of inhibitory
      learning and the explicit model for behavior therapy. Many studies support a
      general learning rule for acquisition: Temporally spaced training is more
      effective than massed training. The authors asked whether this rule applies to
      extinction of conditional fear in mice. The authors find that both short- and
      long-term fear extinction are greater with temporally massed presentations of the
      conditional stimulus (CS). The data also indicate that once CS presentations are
      sufficiently massed to initiate, or "induce," extinction learning, further CS
      presentations are more effective when spaced.

PMID- 14570520
TI  - Differential effects of forward or simultaneous conditioned stimulus
      unconditioned stimulus intervals on the defensive behavior system of the Norway
      rat (Rattus norvegicus).
AB  - To test several predictions derived from a behavior-systems approach, the authors
      assessed Pavlovian fear conditioning in rats after 30 trials of forward,
      simultaneous, or unpaired training. Direct evidence of conditioned fear was
      collected through observation of flight and freezing reactions during
      presentations of the conditioned stimulus (CS) alone. The authors also tested the
      CS's potential to reinforce an instrumental escape response in an escape-from
      fear paradigm. On the one hand, rats that received forward training showed
      conditioned freezing, but no conditioned flight was observed. On the other hand,
      rats that received simultaneous training showed conditioned flight, but no
      conditioned freezing was observed. Rats that received either forward or
      simultaneous pairings showed instrumental learning of the escape-from-fear
      response. Implications for several theories of Pavlovian conditioning are
      discussed.

PMID- 14570521
TI  - Managing HIV at the workplace: An empirical study of HIV and HR managers in
      Singapore.
AB  - Drawing from previous research on individual differences, AIDS, and concerns for
      face, the author developed and tested a model examining the predictors (knowledge
      of AIDS transmission, level of homophobia, and concern for face) of AIDS fear and
      its organizational outcomes (perceived organizational consequences of hiring
      people living with HIV and attitudes toward disclosure of HIV-related information
      at the workplace). Data were collected using mail survey. Structural equation
      modeling was used to examine the relationships among these variables for 160
      human resource managers. All of the hypothesized relationships were empirically
      supported. Implications of the research findings for human resource practices are
      discussed.

PMID- 14570522
TI  - Raising voice, risking retaliation: Events following interpersonal mistreatment
      in the workplace.
AB  - This study advances the literature on workplace deviance, addressing retaliation
      victimization in the context of interpersonal mistreatment. Using survey data
      from 1,167 public-sector employees, the authors investigated experiences of work
      retaliation victimization and social retaliation victimization among employees
      who have vocally resisted interpersonal mistreatment. Regression analyses suggest
      that different victim voice mechanisms trigger different forms of retaliation,
      depending on the social positions of the mistreatment victim and instigator.
      Discriminant function analyses demonstrate lower professional, psychological, and
      physical well-being among mistreated employees who have been further victimized
      with retaliation. These analyses also reveal health-related costs associated with
      victim silence--that is, enduring mistreatment without voicing resistance.
      Results are interpreted in light of theory on power, emotions, and justice in
      organizations.

PMID- 14570523
TI  - Shiftwork and environment as interactive predictors of work perceptions.
AB  - Evidence suggests that the work environment may play a role in the elevated risk
      of adverse health outcomes among shiftworkers compared with dayworkers. Perceived
      work environment measures (physical stressors, job demand, job control, skill
      discretion, supervisor support, and safety perceptions) from UK oil industry
      personnel (N=1,867) were analyzed in relation to shiftwork (day/night rotation vs
      daywork) and objective work environment (onshore vs offshore). Age, education,
      job type, and negative affectivity were also included. The Environment *
      Shiftwork interaction was significant in multivariate tests and in 5 of the 6
      univariate analyses. Onshore, shiftworkers perceived their environment
      significantly less favorably than dayworkers, but differences were less marked
      offshore. Results are discussed in relation to the demand-control-support model
      of work stress.

PMID- 14570524
TI  - "The very best of the millennium": longitudinal research and the demand-control
      (support) model.
AB  - This study addressed the methodological quality of longitudinal research
      examining R. Karasek and T. Theorell's (1990) demand-control-(support) model and
      reviewed the results of the best of this research. Five criteria for evaluating
      methodological quality were used: type of design, length of time lags, quality of
      measures, method of analysis, and nonresponse analysis. These criteria were
      applied to 45 longitudinal studies, of which 19 (42%) obtained acceptable scores
      on all criteria. These high-quality studies provided only modest support for the
      hypothesis that especially the combination of high demands and low control
      results in high job strain. However, good evidence was found for lagged causal
      effects of work characteristics, especially for self-reported health or well
      being outcomes.

PMID- 14570525
TI  - Trust in management as a buffer of the relationships between overload and strain.
AB  - This study examined the role of trust in management as a moderating factor in
      work overload's impact on personal strain (i.e., burnout, psychological strain,
      and work's interference with family). Participants were 94 employees of an
      accounting firm responding to a survey. The results were supportive of all study
      propositions. Both work overload and trust in management had the expected
      negative and positive main effects on the outcomes variables, respectively. The
      impact of work overload on the outcome variables was moderated by employees'
      trust in management. The significance of these results and areas of future
      research are discussed.

PMID- 14570526
TI  - Workplace safety performance: conscientiousness, cognitive failure, and their
      interaction.
AB  - This research investigated the effects of cognitive failure on workplace safety
      and accidents over 2 studies. It was hypothesized that cognitive failure would
      directly predict safety behavior and workplace accidents and predict these
      outcomes over and above conscientiousness. It was found that cognitive failure
      uniquely accounted for workplace safety behavior and accidents. However, it has
      been suggested by researchers that certain individual differences might interact
      to produce differential effects. Thus, a moderated model was tested examining the
      interaction of cognitive failure and conscientiousness. It was found that
      cognitive failure moderated the relationship between conscientiousness and
      accidents and unsafe work behaviors. Overall, results suggest that cognitive
      failure plays an important part in individual safety behavior, especially when
      conscientiousness is low.

PMID- 14570527
TI  - Improving quality of life in men with prostate cancer: a randomized controlled
      trial of group education interventions.
AB  - Men who were recently treated for prostate cancer (N=250) were randomly assigned
      to a control group, a group education intervention (GE), or a group education
      plus-discussion intervention (GED). Both GE and GED increased prostate cancer
      knowledge. In the year postintervention, men in the GED condition were less
      bothered by sexual problems than men in the control condition, and they were more
      likely to remain steadily employed (93.0%) than men in the GE (75.6%) or control
      (72.5%) conditions. Among noncollege graduates, GED and GE resulted in better
      physical functioning than the control condition, and GED resulted in more
      positive health behaviors than the control or GE condition. Among college
      graduates, controls were comparable with the GE and GED groups in physical
      functioning and positive health behaviors.

PMID- 14570528
TI  - Marital status and quality in middle-aged women: Associations with levels and
      trajectories of cardiovascular risk factors.
AB  - The current study compared cardiovascular risk profiles and trajectories (i.e.,
      within-person changes) of women who were married or cohabitating and who had high
      relationship satisfaction with those of women with moderate or low satisfaction
      and with those of women who were single, divorced, and widowed. Participants were
      493 women from the Healthy Women Study, a prospective investigation of health
      during and after the menopausal transition. Risk factors were measured across
      more than 5 occasions and 13 years, on average. Data were analyzed using a
      multilevel modeling technique. Overall, women in relationships with high
      satisfaction had lower levels of biological, lifestyle, and psychosocial risk
      factors when compared with the other groups. In some cases, women in satisfying
      marriages also showed a lower risk trajectory on risk factors relative to other
      women. Hence, marriage appears to confer health benefits for women, but only when
      marital satisfaction is high.

PMID- 14570529
TI  - A connectionist implementation of the theory of planned behavior: association of
      beliefs with exercise intention.
AB  - The theory of planned behavior suggests attitudes are a product of salient
      beliefs. This study examined whether aggregating salient beliefs was plausible
      within a more biologically centered information-processing environment. A neural
      network was used to examine associations among beliefs relating to exercise
      intention. Data on intentions and behavioral, normative, and control beliefs from
      114 respondents were used to train (by error backpropagation) a neural network to
      associate beliefs with intention. The R-sup-2 between the network's estimated and
      self-reported intention was.66. The network's representation comprised 6 belief
      profiles associated with high, moderate, or low behavioral intention. The neural
      network accommodated complex relationships among beliefs and belief-intention
      associations and indicated how high-level constructs such as attitudes may be
      viewed as the best fit (compromise state) between aroused beliefs.

PMID- 14570530
TI  - Observer ratings of health and sickness: can other people tell us anything about
      our health that we don't already know?
AB  - After administering interviews covering health conditions, physical limitations,
      optimism, and affect to 851 older adults, interviewers rated the health and
      sickness of the interviewees. Observers' ratings of health and sickness were more
      highly correlated with the severity of participants' self-reported health
      conditions than were participants' self-ratings of health. This finding is likely
      attributable to participants' self-ratings of health being more highly correlated
      with their optimism and positive affect than the observers' ratings. Participants
      rated as sicker and less healthy at baseline were at a 3 times greater risk for
      mortality over 114 months. This association was independent of participants' self
      rated health as well as demographics, self-reported health conditions, years of
      smoking, physical limitations, body mass index, optimism, and affect.

PMID- 14570531
TI  - Pluralistic ignorance and college student perceptions of gender-specific alcohol
      norms.
AB  - Students' perceived norms and personal concern about alcohol use were examined in
      4 (N=971) experiments. Men reported that same-sex peers were less concerned about
      campus alcohol practices than themselves or female students; women believed that
      they were more concerned about campus alcohol practices than both same- and
      opposite-sex peers (Experiments 1 and 2). Additional evidence suggested that
      students were not merely engaging in impression management. Men reported more
      social pressure to drink and greater embarrassment about expressing drinking
      related concerns; women expected more severe consequences if they drank
      excessively (Experiment 3). A male student (vs female student) expressing
      concerns about alcohol was believed to experience greater difficulties fitting in
      (Experiment 4). Implications for peer influence and drug use intervention are
      discussed.

PMID- 14570532
TI  - The yellow brick road and the emerald city: benefit finding, positive reappraisal
      coping and posttraumatic growth in women with early-stage breast cancer.
AB  - Predictors and outcomes of benefit finding, positive reappraisal coping, and
      posttraumatic growth were examined using interviews and questionnaires from a
      longitudinal study of women with early-stage breast cancer followed from primary
      medical treatment completion to 3 (n=92) and 12 months (n=60) later. Most women
      (83%) reported at least 1 benefit of their breast cancer experience. Benefit
      finding (i.e., identification of benefits, number of benefits), positive
      reappraisal coping, and posttraumatic growth had distinct significant predictors.
      Positive reappraisal coping at study entry predicted positive mood and perceived
      health at 3 and 12 months and posttraumatic growth at 12 months, whereas benefit
      finding did not predict any outcome. Findings suggest that benefit finding,
      positive reappraisal coping, and posttraumatic growth are related, but distinct,
      constructs.

PMID- 14570533
TI  - Depressed versus nondepressed young adult tobacco users: differences in coping
      style, weight concerns and exercise level.
AB  - Undergraduates age 18 to 24 years (n=656) completed questionnaires assessing
      tobacco use, depressive symptoms, coping responses, weight concerns, and
      exercise. The majority of participants were female (72%), White/non-Hispanic
      (95%), and in the 1st or 2nd year of college (80%). Current tobacco users (n=236)
      had a higher frequency of depression (40%) than never tobacco users (32%; p=.05).
      Tobacco users classified as depressed (Center for Epidemiological Studies
      Depression Scale [CES-D] score a 16) reported greater weight concerns and more
      frequent maladaptive coping in response to negative mood than tobacco users
      classified as nondepressed (CES-D score<16). Multivariate logistic regression
      analysis indicated that higher maladaptive coping and lower level of exercise
      were significantly associated with depression among tobacco users.

PMID- 14570534
TI  - Contributions of disease severity and perceptions of primary and secondary
      control to the prediction of psychosocial adjustment to Parkinson's disease.
AB  - Seventy-four people with Parkinson's disease (PD) completed questionnaires and
      were interviewed to determine the degree to which the severity of PD and
      perceptions of primary and secondary control over PD predicted psychosocial
      adjustment. Significant unique contributions to PD-related participation
      restrictions were made by disease severity (positive relationship) and perceived
      internal secondary control (negative relationship). Also, participation
      restrictions had a significant direct effect, and disease severity and perceived
      internal secondary control significant indirect effects, on both depressive
      symptomatology and life satisfaction. Results are consistent with theories that
      suggest the importance of enhancing internal secondary control processes in
      situations in which actual control over objective circumstances is limited, such
      as with chronic and progressive diseases like PD.

PMID- 14570535
TI  - The effects of widowhood on physical and mental health, health behaviors, and
      health outcomes: The Women's Health Initiative.
AB  - This study examined whether widowhood was associated with physical and mental
      health, health behaviors, and health outcomes using a cross-sectional (N=72,247)
      and prospective (N=55,724) design in women aged 50-79 years participating in the
      Women's Health Initiative observational study (85.4% White). At baseline, married
      women reported better physical and mental health and generally better health
      behaviors than widowed women. Whereas women who remained married over the 3-year
      period showed stability in mental health, recent widows experienced marked
      impairments and longer term widows showed stability or slight improvements. Both
      groups of widows reported more unintentional weight loss over the 3-year period.
      Changes in physical health and health behaviors were inconsistent, with generally
      small effect sizes. Findings underscore the resilience of older women and their
      capacity to reestablish connections, but point to the need for services that
      strengthen social support among women who have difficulty during this transition.

PMID- 14570536
TI  - Misperceived risk among female adolescents: social and psychological factors
      associated with sexual risk accuracy.
AB  - This study of 411 urban female adolescents had 3 objectives: (a) assess the
      relationship between perceived risk and sexual risk behavior (condom use, number
      of partners, partner risk, presence of STDs, and aggregate sexual risk), (b)
      assess the accuracy of risk perceptions, and (c) identify variables related to
      inaccurate sexual risk perceptions. Participants were classified as accurate or
      inaccurate risk perceivers on the basis of actual sexual behavior and perceived
      risk. Accurate versus inaccurate risk perceivers were compared on psychological
      maintenance variables (self-esteem, distress, and coping), relationship context
      variables (partnership duration and pressure to have unprotected sex), and risk
      knowledge at different levels of sexual risk. Approximately half of the
      participants underestimated the risk of their sexual behavior. Accurate and
      inaccurate risk perceivers differed on risk knowledge, partnership duration, and
      pressure to have unprotected sex.

PMID- 14570537
TI  - Stigma, social risk, and health policy: public attitudes toward HIV surveillance
      policies and the social construction of illness.
AB  - Data from a 1999 national telephone survey with a probability sample of English
      speaking US adults (N=1,335) were used to assess how support for HIV surveillance
      policies is related to AIDS stigma and negative attitudes toward groups
      disproportionately affected by the epidemic. Anonymous reporting of HIV results
      to the government was supported by a margin of approximately 2-to-l, but name
      based reporting was opposed 3-to-l. Compared with other respondents, supporters
      of name-based surveillance expressed significantly more negative feelings toward
      people with AIDS, gay men, lesbians, and injecting drug users. More than one
      third of all respondents reported that concerns about AIDS stigma would affect
      their own decision to be tested for HIV in the future. Implications for
      understanding the social construction of illness and for implementing effective
      HIV surveillance programs are discussed.

PMID- 14570539
TI  - Comparison of the effects of early handling and early deprivation on conditioned
      stimulus, context, and spatial learning and memory in adult rats.
AB  - Effects of manipulations of the rat pup-dam relationship on affective learning
      and memory in adulthood have received scant systematic investigation. The authors
      previously described how early handling (EH; 15 min isolation/day) and early
      deprivation (ED; 4 hr isolation/day) exert similar effects on spontaneous adult
      affect (open-field behavior, acoustic startle, endocrine stress response)
      relative to nonhandling (NH; C. R. Pryce, D. Bettschen, N. I. Bahr, & J. Feldon,
      2001). The present study demonstrates that both EH and ED adults exhibit enhanced
      active avoidance relative to NH adults. Fear-conditioned context and conditioned
      stimulus (CS) freezing were unaffected in both EH and ED, but stress hormone
      responses to the CS were reduced in EH males and ED females relative to NH. In
      the water maze, ED adults exhibited enhanced spatial learning and memory relative
      to NH.

PMID- 14570538
TI  - Effects of dopamine transporter and receptor polymorphisms on smoking cessation
      in a bupropion clinical trial.
AB  - This study examined the role of dopaminergic genes in prospective smoking
      cessation and response to bupropion treatment in a placebo-controlled clinical
      trial. Smokers of European ancestry (N=418) provided blood samples for genetic
      analysis and received either bupropion or placebo (10 weeks) plus counseling.
      Assessments included the dopamine D2 receptor (DRD2) genotype, dopamine
      transporter (SLC6A3) genotype, demographic factors, and nicotine dependence.
      Smoking status was verified at the end of treatment (EOT) and at 6-month follow
      up. The results provided evidence for a significant DRD2 * SLC6A3 interaction
      effect on prolonged smoking abstinence and time to relapse at EOT, independent of
      treatment condition. Such effects were no longer significant at 6-month follow
      up, however. These results provide the first evidence from a prospective clinical
      trial that genes that alter dopamine function may influence smoking cessation and
      relapse during the treatment phase.

PMID- 14570540
TI  - Neonatal handling reduces the number of cells in the locus coeruleus of rats.
AB  - Neonatal handling induces long-lasting effects on behaviors and stress responses.
      The objective of the present study was to analyze the effects of neonatal
      handling (from the 1st to the 10th day after delivery) on the number of cells and
      volume of locus coeruleus (LC) nucleus in male and female rats at 4 different
      ages: 11, 26, 35, and 90 days. Results showed significant reductions in the
      number of cells and the volume of the LC nucleus in neonatally handled males and
      females compared with nonhandled rats. Environmental stimulation early in life
      induced a stable structural change in a central noradrenergic nucleus, which
      could be one of the causal factors for the behavioral and hormonal alterations
      observed in adulthood.

PMID- 14570541
TI  - Effects of pubertal anabolic-androgenic steroid (AAS) administration on
      reproductive and aggressive behaviors in male rats.
AB  - Adolescence in human males is a hormonally sensitive period when many adult
      behaviors develop, including sexual and aggressive behaviors. Using a rat model,
      the authors examined the effects of three anabolic-androgenic steroids (AAS)
      during puberty: testosterone, nandrolone, and stanozolol. Copulation,
      vocalizations, scent-marking, and aggression were tested following AAS exposure.
      Relative to gonadally intact controls, rats injected with testosterone showed a
      significant increase in scent-marking and aggression in the opponent's home cage.
      Nandrolone had no effect. Stanozolol significantly inhibited all behaviors.
      Results suggest that depending on the chemical structure of the steroid, AAS
      exposure during puberty affects several androgen-dependent behaviors. Because
      adolescence in humans is a period of hormonal change, abuse of AAS, particularly
      stanozolol, during this time may disrupt the establishment of normal adult
      behavior patterns.

PMID- 14570542
TI  - In utero cocaine, discriminative avoidance learning with low-salient stimuli and
      learning-related neuronal activity in rabbits (Oryctolagus cuniculus).
AB  - Daily injections of cocaine administered to pregnant rabbits (Oryctolagus
      cuniculus) throughout gestation were associated with neural and behavioral
      changes during development and in adulthood, including altered neuron structure
      and function in areas receiving dopaminergic projections and retarded Pavlovian
      eyeblink conditioning with low-salient conditional stimuli. Studies of
      discriminative avoidance learning have shown changes in learning-related
      cingulothalamic neuronal activity, but no behavioral learning impairment in
      cocaine-exposed offspring. Here, low-salient stimuli were used during
      discriminative avoidance conditioning. Impairments early in behavioral
      acquisition were found, as well as alterations of anterior cingulate and medial
      prefrontal cortical, medial dorsal thalamic, and amygdalar neuronal response
      profiles and learning-related neuronal activity. These results elucidate the
      neural processes, impaired by prenatal cocaine, that support conditioning with
      low-salient stimuli.

PMID- 14570543
TI  - Oral cocaine seeking by rats: action or habit?
AB  - Having established that the presence of cocaine in a 10% (wt/vol) sucrose
      solution enhanced the reinforcing properties of the solution in a dose-dependent
      manner, the authors investigated the susceptibility of oral cocaine seeking to
      outcome devaluation. Rats were trained to perform different instrumental
      responses for a cocaine-sucrose and a lemon-sucrose solution. An aversion was
      then conditioned from either the cocaine-sucrose or the lemon-sucrose solution by
      pairing consumption with lithium chloride. When instrumental performance was
      subsequently tested in extinction, the rats performed the lemon-sucrose response
      less if this solution, rather than cocaine-sucrose, had been devalued by aversion
      conditioning. By contrast, performance of the cocaine-sucrose response was
      unaffected by whether the cocaine-sucrose or the lemon-sucrose solution had been
      devalued.

PMID- 14570544
TI  - Development and adult phase plasticity of syllable repetitions in the birdsong of
      captive zebra finches (Taeniopygia guttata).
AB  - Oscines learn their birdsongs from tutors. The authors found that a small
      fraction (approximately 7%) of captive male zebra finches (Taeniopygia guttata)
      produce variant acoustic birdsong profiles consisting of repetitions of single
      song syllables at high frequencies. Juvenile offspring of nonrepeaters can
      selectively learn the syntactic rule or habit of repeating syllables from
      repeaters. Adult tutored syllable repeaters, unlike spontaneous repeaters,
      undergo a form of song plasticity involving progressive reduction of the mean
      number and variance of repeated syllables as a function of long-term exposure to
      nonrepeater songs without altering the number or sequence of syllables within
      motifs. These findings suggest that aspects of song syntax or temporal frame can
      be acquired independently of song syllable or spectral content, and plasticity
      involving restorative alteration of acquired variant temporal frames can occur
      after the closure of the critical period for song learning.

PMID- 14570545
TI  - Differential control over drug-seeking behavior by drug-associated conditioned
      reinforcers and discriminative stimuli predictive of drug availability.
AB  - Conditioned stimuli (CSs) can control behavior either by activating responses
      when presented noncontingently or through their ability to maintain responding
      when presented contingently, that is, as conditioned reinforcers. In the present
      study, the extent to which drug-seeking behavior could be subject to these
      different types of stimulus control was studied by presenting to rats CSs that
      were either paired with each drug infusion or presented as discriminative stimuli
      (DSs) signaling the availability of drug. It was found that stimuli paired with
      either cocaine or heroin infusions increased drug seeking when presented
      contingent on responding, but not when presented noncontingently. By contrast,
      DSs that signaled cocaine availability increased drug seeking when presented
      either noncontingently or contingently. These results suggest that drug-seeking
      behavior can be influenced differentially by CSs and that conditioned reinforcers
      are especially important for maintaining prolonged sequences of drug-seeking
      behavior.

PMID- 14570546
TI  - Amphetamine sensitization: nonassociative and associative components.
AB  - Rats, pretreated with amphetamine (AMPH, 1 mg/kg) or saline for 2 weeks, were
      challenged with AMPH (0.5 mg/kg) or saline following 1 week of abstinence, and
      locomotion was measured. In Experiments 1 and 2, the pretreatment occurred in
      various contexts (home cage, novel box, test box). Sensitization was observed
      only when pretreatment context and test context were the same; a context switch
      abolished sensitization. When rats anesthetized with chloral hydrate were
      pretreated with AMPH, sensitization was completely dependent on the pretreatment,
      but independent of context. This "zero context" condition isolated the basal
      level of excitation attributable to unconditioned neural change to determine the
      role of contextual input to be a modulator that enhances or inhibits
      sensitization.

PMID- 14570547
TI  - Lack of depression-like effects of saccharin deprivation in rats: forced swim
      test, differential reinforcement of low rates and intracranial self-stimulation
      procedures.
AB  - In humans and laboratory animals, drug withdrawal often is associated with
      depression-like behaviors. In the present study, rats had unlimited free-choice
      access to water and a saccharin-containing solution before being subjected to
      repeated episodes of saccharin deprivation. Saccharin deprivation (1) reduced
      immobility time in the forced swim test, (2) increased reinforcement rate in rats
      trained to lever-press under the differential reinforcement of a low-rate (72
      sec) schedule of food reinforcement, and (3) lowered intracranial self
      stimulation thresholds in a discrete-trial current titration procedure. Taken
      together, these findings suggest that deprivation from a nondrug reinforcer,
      saccharin, is not associated with depression-like behaviors. In contrast,
      saccharin-deprived rats demonstrated improved performance in the behavioral
      paradigms used here.

PMID- 14570548
TI  - Growth of brain stimulation reward as a function of duration and stimulation
      strength.
AB  - The strength of a train of rewarding brain stimulation required to support a
      criterion level of operant performance declines hyperbolically as the duration is
      increased. This finding has been attributed to a process of leaky integration.
      However, the rate at which integration approaches asymptote has been shown to
      depend on stimulation strength, a finding that differs from the behavior of a
      simple leaky integrator. The authors replicate both findings and show that they
      are both well described by a new model that incorporates a hyperbolic strength
      duration function, a logistic function mapping stimulation frequency onto reward
      intensity, and another logistic function mapping reward intensity onto
      performance.

PMID- 14570549
TI  - Changes in dopaminergic neurotransmission do not alter somatic or motivational
      opiate withdrawal-induced symptoms in rats.
AB  - Opiate withdrawal has been correlated with decreased extracellular dopamine (DA)
      levels in the nucleus accumbens (NAC) of morphine-dependent rats. The authors
      tested the hypothesis that DA transmission plays a critical role in the induction
      of motivational and somatic withdrawal symptoms. First, the authors used a 6
      hydroxydopamine-induced lesion of the NAC to chronically disrupt mesolimbic DA
      transmission. Second, global DA neurotransmission was acutely stimulated by the
      nonselective DA agonist (apomorphine) or inhibited by nonselective DA antagonists
      (droperidol or flupentixol). Morphine-dependent rats bearing 6-hydroxydopamine
      induced lesions displayed naloxone-precipitated motivational and somatic
      withdrawal symptoms similar to those of sham-lesioned rats. Administration of
      apomorphine did not reduce naloxone-induced opiate withdrawal. Moreover, in total
      absence of naloxone, DA antagonists did not precipitate either conditioned place
      aversion or somatic abstinence signs in dependent rats. Taken together, these
      findings suggested that DA transmission is not critical for the induction of
      opiate withdrawal syndrome.

PMID- 14570550
TI  - Exercise increases hippocampal neurogenesis to high levels but does not improve
      spatial learning in mice bred for increased voluntary wheel running.
AB  - The hippocampus is important for the acquisition of new memories. It is also one
      of the few regions in the adult mammalian brain that can generate new nerve
      cells. The authors tested the hypothesis that voluntary exercise increases
      neurogenesis and enhances spatial learning in mice selectively bred for high
      levels of wheel running (S mice). Female S mice and outbred control (C) mice were
      housed with and without running wheels for 40 days. 5-Bromodeoxyuridine was used
      to label dividing cells. The Morris water maze was used to measure spatial
      learning. C runners showed a strong positive correlation between running distance
      and new cell number, as well as improved learning. In S runners, neurogenesis
      increased to high levels that reached a plateau, but no improvement in learning
      occurred. This is the first evidence that neurogenesis can occur without learning
      enhancement. The authors propose an alternative function of neurogenesis in the
      control of motor behavior.

PMID- 14570551
TI  - Extinction, renewal, and spontaneous recovery of a spatial preference in the
      water maze.
AB  - Four experiments with C57BL/6 mice investigated extinction of a spatial
      preference in the Morris water maze. In Experiment 1, a spatial preference was
      extinguished by exposing mice to the water maze in the absence of a platform but
      in the presence of the distal spatial cues. In Experiment 2, extinction occurred
      when the platform was removed from the pool, when it was presented in random
      locations, or when it was presented consistently in the opposite location.
      Contextual renewal (Experiment 3) and spontaneous recovery (Experiment 4) of
      spatial preferences argue against an interpretation of extinction in terms of
      unlearning and instead suggest that extinction in the water maze, like extinction
      in Pavlovian conditioning, suppresses the original association. Implications of
      these findings for theories of spatial learning and hippocampal function are
      discussed.

PMID- 14570552
TI  - Selective neurotoxic amygdala lesions in monkeys disrupt reactivity to food and
      object stimuli and have limited effects on memory.
AB  - Monkeys with bilateral neurotoxic amygdala lesions and normal monkeys were
      administered tests of emotional reactivity, recognition memory, and reward
      association memory. There were 3 main findings. First, monkeys with amygdala
      lesions performed differently than normal monkeys on initial administrations of
      the emotional reactivity tests and on retests that were given 21-23 months after
      surgery. Second, they performed like normal monkeys on tests of recognition
      memory. Third, they were initially impaired on a test of reward association
      memory, but they were not impaired on a retest that was given 16 months after
      surgery. These findings underscore the role of the amygdala in aspects of
      emotional reactivity and reward association memory, but not in recognition
      memory. In addition, at least some of the behavioral effects of amygdala damage
      can be long lasting.

PMID- 14570553
TI  - Differential roles of dorsal hippocampal subregions in spatial working memory
      with short versus intermediate delay.
AB  - In order to determine the role of subregions of the hippocampus in spatial
      working memory, this study combined selective neurotoxic lesions of the
      hippocampal subregions with a simple delayed nonmatching-to-place task on a
      radial maze in rats. Lesions of the dentate gyrus or the CA3, but not the CA1,
      subregion of the hippocampus induced a deficit in the acquisition of the task
      with short-term delays (i.e., 10 sec) and impaired performance of the task in a
      novel environment. All subregional lesions produced sustained impairment in
      performing the task with intermediate-term delays (i.e., 5 min) when rats were
      tested in a familiar environment. The results suggest a dynamic interaction among
      the dorsal hippocampal subregions in processing spatial working memory, with the
      time window (i.e., delay) of a task recognized as an essential controlling
      factor.

PMID- 14570554
TI  - The contribution of the rat prelimbic-infralimbic areas to different forms of
      task switching.
AB  - The experiments examined the effects of prelimbic-infralimbic inactivation in
      rats on the acquisition and reversal learning of different discrimination tasks:
      2- or 4-choice odor discrimination in Experiments 1 and 2, the shift from 2
      choice odor discrimination to 2-choice place discrimination in Experiment 3, and
      the shift from 2-choice place to 2-choice odor discrimination in Experiment 4.
      Infusions of 2% bupivacaine did not impair performance in the odor discrimination
      tests. Prelimbic-infralimbic inactivation did not impair acquisition but did
      impair the shift from an odor to a place discrimination and vice versa. Analysis
      of the errors revealed that the deficit was due to perseveration of the
      previously learned strategy. The selective deficits observed in the odor-place
      tests suggest that the prelimbic-infralimbic areas enable behavioral flexibility
      when conditions demand inhibiting the use of one type of attribute information
      and learning a new type of attribute information.

PMID- 14570555
TI  - Response latency in Canis familiaris: mental ability or mental strategy?
AB  - Animal studies of cognitive aging typically use measures of response accuracy
      (RA) to evaluate cognitive function, which declines with age. Human aging
      studies, by contrast, frequently measure response latency (RL), with faster
      responses being indicative of superior performance. To examine the influence of
      age on RL in an animal model, the authors assessed RA with RL in young and aged
      beagle dogs (Canis familiaris) tested on a 3-component delayed nonmatching-to
      position task, which comprised 3 subtests. Young dogs displayed significantly
      slower RLs and higher RAs and showed RL slowing with greater complexity, compared
      with aged dogs. In addition, the slower responding young dogs made fewer errors.
      Thus, RL appears to reflect the learning strategy applied, rather than the level
      of mental ability.

PMID- 14570556
TI  - Anticonvulsant drugs differentially suppress individual ictal signs: a
      pharmacokinetic/pharmacodynamic analysis in the cortical stimulation model in the
      rat.
AB  - Antiepileptic drugs can suppress seizures completely, but they may also modify
      the appearance of drug-resistant seizures. In this study, the effects of three
      antiepileptic drugs on a seizure pattern were assessed by means of population
      pharmacokinetic/pharmacodynamic (PK/PD) modeling, yielding estimates of baseline
      response, EC50, and Hill slope. Lamotrigine did not affect eye closure, although
      it did suppress the other ictal signs in a concentration-dependent fashion.
      Midazolam suppressed forelimb clonus less potently than the other ictal signs;
      the same was observed for tiagabine with respect to eye closure. This study shows
      that ictal component analysis (ICA) in combination with PK/PD modeling may
      facilitate drug selection and dose optimization. The application of ICA is not
      restricted to a single seizure type or anticonvulsant drug and can be used to
      identify drug combinations that have a complementary action.

PMID- 14570557
TI  - Slime-trail tracking in the predatory snail, Euglandina rosea.
AB  - Euglandina rosea, a predatory land snail, tracks prey and mates by following
      slime trails. Euglandina follow slime trails more than 80% of the time, following
      trails of their own species, but not those of prey snails, in the direction that
      they were laid. The attractive elements of prey slime are small, water-soluble
      compounds detected by specialized lip extensions. Although olfaction plays no
      role in trail following, strong odors disrupt tracking. Inhibition of nitric
      oxide synthase also disrupts slime trail following, suggesting a role for nitric
      oxide in neural processing of slime trail stimuli. Euglandina can be conditioned
      to follow novel trails of glutamate or arginine paired with feeding on prey
      snails. These experiments demonstrate that slime-trail tracking in Euglandina is
      a robust, easily measured behavior that makes a good model system for studying
      sensory processing and learning in a novel modality.

PMID- 14570558
TI  - Sexual orientation-related differences in prepulse inhibition of the human
      startle response.
AB  - Prepulse inhibition (PPI) refers to a reduction in the startle response to a
      strong sensory stimulus when this stimulus is preceded by a weaker stimulus--the
      prepulse. PPI reflects a nonlearned sensorimotor gating mechanism and also shows
      a robust gender difference, with women exhibiting lower PPI than men. The present
      study examined the eyeblink startle responses to acoustic stimuli of 59 healthy
      heterosexual and homosexual men and women. Homosexual women showed significantly
      masculinized PPI compared with heterosexual women, whereas no difference was
      observed in PPI between homosexual and heterosexual men. These data provide the
      first evidence for within-gender differences in basic sensorimotor gating
      mechanisms and implicate the known neural substrates of PPI in human sexual
      orientation.

PMID- 14570559
TI  - Conditioned facilitation of brain reward function after repeated cocaine
      administration.
AB  - Cocaine lowers brain reward thresholds, reflecting increased brain reward
      function. The authors investigated whether, similar to acute cocaine
      administration, cocaine-predictive conditioned stimuli would lower intracranial
      self-stimulation (ICSS) thresholds. Rats received a saline injection for 5 days,
      a cocaine injection (10 mg/kg) for 20 consecutive days, then saline for 5
      additional days. Thresholds were measured immediately before and 10 min after
      each injection. The initial 5 saline injections had no effect on thresholds,
      whereas cocaine significantly lowered thresholds for 20 days. There was no
      tolerance or sensitization to this effect of cocaine over days. During the last 5
      days when cocaine administration was substituted with saline, rats demonstrated a
      conditioned lowering of thresholds during the 2nd daily ICSS session. These data
      demonstrate that cocaine-predictive conditioned stimuli induce a conditioned
      facilitation of brain reward function.

PMID- 14570560
TI  - Receptor contributions to configural and elemental odor mixture perception.
AB  - Odor mixture perception can be configural (the mixture is qualitatively different
      from the components) or elemental (the components are recognizable). Some have
      argued that configural properties are dependent on chemical similarity and
      possible overlap at the receptor level. The authors show that a binary mixture in
      which both components activate the same receptor (17) has a configural odor,
      whereas a mixture that suppresses overlap has elemental odor properties. Rats
      trained to recognize mixtures of citronellal and octanal (strong 17 agonists) in
      many ratios rarely recognize the components, supporting configural representation
      of the odor mixture. However, when trained to recognize mixtures of citral
      (partial 17 agonist, inhibitor) and octanal, rats recognize 1 or both components
      over a wide range of ratios.

PMID- 14570561
TI  - Adult stem cell plasticity: fact or artifact?
AB  - There has been unprecedented recent interest in stem cells, mainly because of the
      hope they offer for cell therapy. Adult stem cells are an attractive source of
      cells for therapy, especially in view of the recent claims that they are
      remarkably plastic in their developmental potential when exposed to new
      environments. Some of these claims have been either difficult to reproduce or
      shown to be misinterpretations, leaving the phenomenon of adult stem cell
      plasticity under a cloud. There are, however, other examples of plasticity where
      differentiated cells or their precursors can be reprogrammed by extracellular
      cues to alter their character in ways that could have important implications for
      cell therapy and other forms of regenerative treatment.

PMID- 14570562
TI  - Cyclic nucleotide-gated ion channels.
AB  - Cyclic nucleotide-gated (CNG) ion channels were first discovered in rod
      photoreceptors, where they are responsible for the primary electrical signal of
      the photoreceptor in response to light. CNG channels are highly specialized
      membrane proteins that open an ion-permeable pore across the membrane in response
      to the direct binding of intracellular cyclic nucleotides. CNG channels have been
      identified in a number of other tissues, including the brain, where their roles
      are only beginning to be appreciated. Recently, significant progress has been
      made in understanding the molecular mechanisms underlying their functional
      specializations. From these studies, a picture is beginning to emerge for how the
      binding of cyclic nucleotide is transduced into the opening of the pore and how
      this allosteric transition is modulated by various physiological effectors.

PMID- 14570563
TI  - Anthrax toxin.
AB  - Anthrax toxin consists of three nontoxic proteins that associate in binary or
      ternary combinations to form toxic complexes at the surface of mammalian cells.
      One of these proteins, protective antigen (PA), transports the other two, edema
      factor (EF) and lethal factor (LF), to the cytosol. LF is a Zn2+-protease that
      cleaves certain MAP kinase kinases, leading to death of the host via a poorly
      defined sequence of events. EF, a calmodulin- and Ca2+-dependent adenylate
      cyclase, is responsible for the edema seen in the disease. Both enzymes are
      believed to benefit the bacteria by inhibiting cells of the host's innate immune
      system. Assembly of toxic complexes begins after PA binds to cellular receptors
      and is cleaved into two fragments by furin proteases. The smaller fragment
      dissociates, allowing the receptor-bound fragment, PA63 (63 kDa), to self
      associate and form a ring-shaped, heptameric pore precursor (prepore). The
      prepore binds up to three molecules of EF and/or LF, and the resulting complexes
      are endocytosed and trafficked to an acidic compartment. There, the prepore
      converts to a transmembrane pore, mediating translocation of EF and LF to the
      cytosol. Recent studies have revealed (a) the identity of receptors; (b)
      crystallographic structures of the three toxin proteins and the heptameric PA63
      prepore; and (c) information about toxin assembly, entry, and action within the
      cytosol. Knowledge of the structure and mode of action of the toxin has unveiled
      potential applications in medicine, including approaches to treating anthrax
      infections.

PMID- 14570564
TI  - Genes, signals, and lineages in pancreas development.
AB  - Type I diabetes results from the autoimmune-mediated destruction of pancreatic
      beta cells, which regulate blood sugar levels by secretion of insulin. Recent
      clinical data suggest that the disease could be cured if an adequate supply of
      new beta-cells were available, and one goal of pancreatic developmental biology
      is to understand how endogenous beta-cells are made, with the hope of making them
      exogenously. Much is now known about the transcriptional regulation of pancreatic
      organ specification, growth, and lineage allocation; less is known about
      intercellular signals that regulate this process, but candidates continue to
      emerge. Additional insights, often contradicting older models, have come from the
      application of new lineage-tracing techniques. Altogether, these studies also
      shed light on the still-elusive pancreatic stem cell, which may participate in
      normal organ maintenance as well as recovery from injury. A rigorous proof of the
      existence of such a cell, whether in vivo or in vitro, would offer real hope for
      the prospect of controlled beta-cell generation in a clinical setting.

PMID- 14570565
TI  - Regulation of MAP kinase signaling modules by scaffold proteins in mammals.
AB  - The mitogen-activated protein kinase (MAPK) group of serine/threonine protein
      kinases mediates the response of cells to many extracellular stimuli such as
      cytokines and growth factors. These protein kinases include the extracellular
      signal-regulated protein kinases (ERK) and two stress-activated protein kinases
      (SAPK), the c-Jun N-terminal kinases (JNK), and the p38 MAPK. The enzymes are
      evolutionarily conserved and are activated by a common mechanism that involves a
      protein kinase cascade. Scaffold proteins have been proposed to interact with
      MAPK pathway components to create a functional signaling module and to control
      the specificity of signal transduction. Here we critically evaluate the evidence
      that supports a physiologically relevant role of MAPK scaffold proteins in
      mammals.

PMID- 14570566
TI  - Flower development: initiation, differentiation, and diversification.
AB  - Flowering is one of the most intensively studied processes in plant development.
      Despite the wide diversity in floral forms, flowers have a simple stereotypical
      architecture. Flowers develop from florally determined meristems. These small
      populations of cells proliferate to form the floral organs, including the sterile
      outer organs, the sepals and petals, and the inner reproductive organs, the
      stamens and carpels. In the past decade, analyses of key flowering genes have
      been carried out primarily in Arabidopsis and have provided a foundation for
      understanding the underlying molecular genetic mechanisms controlling different
      aspects of floral development. Such studies have illuminated the transcriptional
      cascades responsible for the regulation of these key genes, as well as how these
      genes effect their functions. In turn, these studies have resulted in the
      refinement of the original ideas of how flowers develop and have indicated the
      gaps in our knowledge that need to be addressed.

PMID- 14570567
TI  - Regulation of membrane protein transport by ubiquitin and ubiquitin-binding
      proteins.
AB  - Ubiquitin regulates protein transport between membrane compartments by serving as
      a sorting signal on protein cargo and by controlling the activity of trafficking
      machinery. Monoubiquitin attached to integral plasma membrane proteins or to
      associated transport modifiers serves as a regulated signal for internalization
      into the endocytic pathway. Similarly, monoubiquitin attached to biosynthetic and
      endocytic membrane proteins is a signal for sorting of cargo into vesicles that
      bud into the late endosome lumen for delivery into the lysosome. Ubiquitination
      of trans-acting endocytic proteins is also required for transport, and key
      endocytic proteins are modified by monoubiquitin. Regulatory enzymes of the
      ubiquitination machinery, ubiquitin ligases, control the timing and specificity
      of plasma membrane protein downregulation in such diverse biological processes as
      cell fate specification and neurotransmission. Monoubiquitin signals appended by
      these ligases are recognized by endocytic proteins carrying ubiquitin-binding
      motifs, including UBA, UEV, UIM, and CUE domains. The UIM proteins epsins and Hrs
      are excellent candidates for adaptors that link ubiquitinated cargo to the
      clathrin-based sorting machinery at appropriate regions of the endosomal or
      plasma membranes. Other ubiquitin-binding proteins also play crucial roles in
      cargo transport, although in most cases the role of ubiquitin-binding is not
      defined. Ubiquitin-binding proteins such as epsins, Hrs, and Vps9 are
      monoubiquitinated, indicating the general nature of ubiquitin regulation in
      endocytosis and suggesting new models to explain how recognition of monoubiquitin
      signals may be regulated.

PMID- 14570568
TI  - Positional control of cell fate through joint integrin/receptor protein kinase
      signaling.
AB  - Cells adhere to the extracellular matrix throughout most of their lifetime. This
      close, intimate contact with the matrix exerts an extraordinary control on the
      behavior of cells, determining whether they move or stay put, proliferate or
      remain quiescent, and even live or die. Attachment to the matrix not only enables
      cells to respond to soluble growth factors and cytokines but also determines the
      nature of the response. The integrins are a large family of receptors that attach
      cells to the matrix, organize their cytoskeleton, and cooperate with receptor
      protein tyrosine kinases to regulate cell fate. Research on integrin signaling is
      beginning to explain the complex and specific effects that the extracellular
      matrix exerts on cells.

PMID- 14570569
TI  - Cadherins as modulators of cellular phenotype.
AB  - Cadherins are transmembrane glycoproteins that mediate calcium-dependent cell
      cell adhesion. The cadherin family is large and diverse, and proteins are
      considered to be members of this family if they have one or more cadherin repeats
      in their extracellular domain. Cadherin family members are the transmembrane
      components of a number of cellular junctions, including adherens junctions,
      desmosomes, cardiac junctions, endothelial junctions, and synaptic junctions.
      Cadherin function is critical in normal development, and alterations in cadherin
      function have been implicated in tumorigenesis. The strength of cadherin
      interactions can be regulated by a number of proteins, including the catenins,
      which serve to link the cadherin to the cytoskeleton. Cadherins have been
      implicated in a number of signaling pathways that regulate cellular behavior, and
      it is becoming increasingly clear that integration of information received from
      cell-cell signaling, cell-matrix signaling, and growth factor signaling
      determines ultimate cellular phenotype and behavior.

PMID- 14570570
TI  - Genomic imprinting: intricacies of epigenetic regulation in clusters.
AB  - An intriguing characteristic of imprinted genes is that they often cluster in
      large chromosomal domains, raising the possibility that gene-specific and domain
      specific mechanisms regulate imprinting. Several common features emerged from
      comparative analysis of four imprinted domains in mice and humans: (a) Certain
      genes appear to be imprinted by secondary events, possibly indicating a lack of
      gene-specific imprinting marks; (b) some genes appear to resist silencing,
      predicting the presence of cis-elements that oppose domain-specific imprinting
      control; (c) the nature of the imprinting mark remains incompletely understood.
      In addition, common silencing mechanisms are employed by the various imprinting
      domains, including silencer elements that nucleate and propagate a silent
      chromatin state, insulator elements that prevent promoter-enhancer interactions
      when hypomethylated on one parental allele, and antisense RNAs that function in
      silencing the overlapping sense gene and more distantly located genes. These
      commonalities are reminiscent of the behavior of genes subjected to, and the
      mechanisms employed in, dosage compensation.

PMID- 14570571
TI  - The COP9 signalosome.
AB  - The COP9 signalosome (CSN) is composed of eight distinct subunits and is highly
      homologous to the lid sub-complex of the 26S proteasome. CSN was initially
      defined as a repressor of photomorphogenesis in Arabidopsis, and it has now been
      found to participate in diverse cellular and developmental processes in various
      eukaryotic organisms. Recently, CSN was revealed to have a metalloprotease
      activity centered in the CSN5/Jab1 subunit, which removes the post-translational
      modification of a ubiquitin-like protein, Nedd8/Rub1, from the cullin component
      of SCF ubiquitin E3 ligase (i.e., de-neddylation). In addition, CSN is associated
      with de-ubiquitination activity and protein kinase activities capable of
      phosphorylating important signaling regulators. The involvement of CSN in a
      number of cellular and developmental processes has been attributed to its control
      over ubiquitin-proteasome-mediated protein degradation.

PMID- 14570572
TI  - Actin assembly and endocytosis: from yeast to mammals.
AB  - Internalization of receptors, lipids, pathogens, and other cargo at the plasma
      membrane involves several different pathways and requires coordinated
      interactions between a variety of protein and lipid molecules. The actin
      cytoskeleton is an integral part of the cell cortex, and there is growing
      evidence that F-actin plays a direct role in these endocytic events. Genetic
      studies in yeast have firmly established a functional connection between actin
      and endocytosis. Identification of several proteins that may function at the
      interface between actin and the endocytic machinery has provided further evidence
      for this association in both yeast and mammalian cells. Several of these proteins
      are directly involved in regulating actin assembly and could thus harness forces
      produced during actin polymerization to facilitate specific steps in the
      endocytic process. Recent microscopy studies in mammalian cells provide powerful
      evidence that localized recruitment and polymerization of actin occurs at
      endocytic sites. In this review, we focus on progress made in elucidating the
      functions of the actin cytoskeleton in endocytosis.

PMID- 14570573
TI  - Transport protein trafficking in polarized cells.
AB  - In order to carry out their physiological functions, ion transport proteins must
      be targeted to the appropriate domains of cell membranes. Regulation of ion
      transport activity frequently involves the tightly controlled delivery of
      intracellular populations of transport proteins to the plasma membrane or the
      endocytic retrieval of transport proteins from the cell surface. Transport
      proteins carry signals embedded within their structures that specify their
      subcellular distributions and endow them with the capacity to participate in
      regulated membrane trafficking processes. Recently, a great deal has been learned
      about the biochemical nature of these signals, as well as about the cellular
      machinery that interprets them and acts upon their messages.

PMID- 14570574
TI  - Modulation of notch signaling during somitogenesis.
AB  - The Notch signaling pathway is known to govern various aspects of tissue
      differentiation during embryonic development by mediating local cell-cell
      interactions that often control cell fate. The conserved components that underlie
      Notch signaling have been isolated in vertebrates, leading to a biochemical
      delineation of a core Notch signaling pathway and functional studies of this
      pathway during embryogenesis. Herein we highlight recent progress in determining
      how Notch signaling contributes to the development of the vertebrate embryo. We
      first discuss the role of Notch in the process of segmentation where rapid
      changes have been shown to occur in both the spatial and temporal aspects of
      Notch signaling, which are critical for segmental patterning. Indeed, the role of
      Notch in segmentation re-emphasizes a recurring question in Notch biology: how
      are the components involved in Notch signaling regulated to ensure their dynamic
      properties? Second, we address this question by discussing recent work on the
      biochemical mechanisms that potentially regulate Notch signaling during
      segmentation, including those that act on the receptors, ligands, and signal
      transduction apparatus.

PMID- 14570575
TI  - Tetraspanin proteins mediate cellular penetration, invasion, and fusion events
      and define a novel type of membrane microdomain.
AB  - This review summarizes key aspects of tetraspanin proteins, with a focus on the
      functional relevance and structural features of these proteins and how they are
      organized into a novel type of membrane microdomain. Despite the size of the
      tetraspanin family and their abundance and wide distribution over many cell
      types, most have not been studied. However, from studies of prototype
      tetraspanins, information regarding functions, cell biology, and structural
      organization has begun to emerge. Genetic evidence points to critical roles for
      tetraspanins on oocytes during fertilization, in fungi during leaf invasion, in
      Drosophila embryos during neuromuscular synapse formation, during T and B
      lymphocyte activation, in brain function, and in retinal degeneration. From
      structure and mutagenesis studies, we are beginning to understand functional
      subregions within tetraspanins, as well as the levels of connections among
      tetraspanins and their many associated proteins. Tetraspanin-enriched
      microdomains (TEMs) are emerging as entities physically and functionally distinct
      from lipid rafts. These microdomains now provide a context in which to evaluate
      tetraspanins in the regulation of growth factor signaling and in the modulation
      of integrin-mediated post-cell adhesion events. Finally, the enrichment of
      tetraspanins within secreted vesicles called exosomes, coupled with hints that
      tetraspanins may regulate vesicle fusion and/or fission, suggests exciting new
      directions for future research.

PMID- 14570576
TI  - Intraflagellar transport.
AB  - It has been a decade since a novel form of microtubule (MT)-based motility, i.e.,
      intraflagellar transport (IFT), was discovered in Chlamydomonas flagella.
      Subsequent research has supported the hypothesis that IFT is required for the
      assembly and maintenance of all cilia and flagella and that its underlying
      mechanism involves the transport of nonmembrane-bound macromolecular protein
      complexes (IFT particles) along axonemal MTs beneath the ciliary membrane. IFT
      requires the action of the anterograde kinesin-II motors and the retrograde IFT
      dynein motors to transport IFT particles in opposite directions along the MT
      polymer lattice from the basal body to the tip of the axoneme and back again. A
      rich diversity of biological processes has been shown to depend upon IFT,
      including flagellar length control, cell swimming, mating and feeding,
      photoreception, animal development, sensory perception, chemosensory behavior,
      and lifespan control. These processes reflect the varied roles of cilia and
      flagella in motility and sensory signaling.

PMID- 14570577
TI  - The dynamic and motile properties of intermediate filaments.
AB  - For many years, cytoplasmic intermediate filaments (IFs) were considered to be
      stable cytoskeletal elements contributing primarily to the maintenance of the
      structural and mechanical integrity of cells. However, recent studies of living
      cells have revealed that IFs and their precursors possess a remarkably wide array
      of dynamic and motile properties. These properties are in large part due to
      interactions with molecular motors such as conventional kinesin, cytoplasmic
      dynein, and myosin. The association between IFs and motors appears to account for
      much of the well-documented molecular cross talk between IFs and the other major
      cytoskeletal elements, microtubules, and actin-containing microfilaments.
      Furthermore, the associations with molecular motors are also responsible for the
      high-speed, targeted delivery of nonfilamentous IF protein cargo to specific
      regions of the cytoplasm where they polymerize into IFs. This review considers
      the functional implications of the motile properties of IFs and discusses the
      potential relationships between malfunctions in these motile activities and human
      diseases.

PMID- 14570578
TI  - Pigment cells: a model for the study of organelle transport.
AB  - Eukaryotic organisms rely on intracellular transport to position organelles and
      other components within their cells. Pigment cells provide an excellent model to
      study organelle transport as they specialize in the translocation of pigment
      granules in response to defined chemical signals. Pigment cells of lower
      vertebrates have traditionally been used as a model for these studies because
      these cells transport pigment organelles in a highly coordinated fashion, are
      easily cultured and transfected, are ideal for microsurgery, and are good for
      biochemical experiments, including in vitro analysis of organelle motility. Many
      important properties of organelle transport, for example, the requirement of two
      cytoskeletal filaments (actin and microtubules), the motor proteins involved, and
      the mechanisms of their regulation and interactions, have been studied using
      pigment cells of lower vertebrates. Genetic studies of mouse melanocytes allowed
      the discovery of essential elements involved in organelle transport including the
      myosin-Va motor and its receptor and adaptor molecules on the organelle surface.
      Future studies of pigment cells will contribute to our understanding of issues
      such as the cooperation among multiple motor proteins and the mechanisms of
      regulation of microtubule motors.

PMID- 14570579
TI  - SNARE protein structure and function.
AB  - The SNARE superfamily has become, since its discovery approximately a decade ago,
      the most intensively studied element of the protein machinery involved in
      intracellular trafficking. Intracellular membrane fusion in eukaryotes requires
      SNARE (soluble N-ethylmaleimide-sensitive-factor attachment protein receptor)
      proteins that form complexes bridging the two membranes. Although common themes
      have emerged from structural and functional studies of SNAREs and other
      components of the eukaryotic membrane fusion machinery, there is still much to
      learn about how the assembly and activity of this machinery is choreographed in
      living cells.

PMID- 14570580
TI  - Structure, function, and regulation of budding yeast kinetochores.
AB  - Kinetochores are multiprotein complexes that assemble on centromeric DNA and
      mediate the attachment and movement of chromosomes along the microtubules (MTs)
      of the mitotic spindle. This review focuses on the simplest eukaryotic
      centromeres and kinetochores, those found in the budding yeast Saccharomyces
      cerevisiae. Research on kinetochore function and chromosome segregation is
      focused on four questions of general significance: what specifies the location of
      centromeres? What are the protein components of kinetochores, and how do they
      assemble a MT attachment site? How do MT attachments generate force? How do cells
      sense the state of attachment via the spindle assembly checkpoint?

PMID- 14570581
TI  - Ena/VASP proteins: regulators of the actin cytoskeleton and cell migration.
AB  - Ena/VASP proteins are a conserved family of actin regulatory proteins made up of
      EVH1, EVH2 domains, and a proline-rich central region. They have been implicated
      in actin-based processes such as fibroblast migration, axon guidance, and T cell
      polarization and are important for the actin-based motility of the intracellular
      pathogen Listeria monocytogenes. Mechanistically, these proteins associate with
      barbed ends of actin filaments and antagonize filament capping by capping protein
      (CapZ). In addition, they reduce the density of Arp2/3-dependent actin filament
      branches and bind Profilin at sites of actin polymerization. Vertebrate Ena/VASP
      proteins are substrates for PKA/PKG serine/threonine kinases. Phosphorylation by
      these kinases appears to modulate Ena/VASP function within cells, although the
      mechanism underlying this regulation remains to be determined.

PMID- 14570582
TI  - Proteolysis in bacterial regulatory circuits.
AB  - Proteolysis by cytoplasmic, energy-dependent proteases plays a critical role in
      many regulatory circuits, keeping basal levels of regulatory proteins low and
      rapidly removing proteins when they are no longer needed. In bacteria, four
      families of energy-dependent proteases carry out degradation. In all of them,
      substrates are first recognized and bound by ATPase domains and then unfolded and
      translocated to a sequestered proteolytic chamber. Substrate selection depends
      not on ubiquitin but on intrinsic recognition signals within the proteins and, in
      some cases, on adaptor or effector proteins that participate in delivering the
      substrate to the protease. For some, the activity of these adaptors can be
      regulated, which results in regulated proteolysis. Recognition motifs for
      proteolysis are frequently found at the N and C termini of substrates.
      Proteolytic switches appear to be critical for cell cycle development in
      Caulobacter crescentus, for proper sporulation in Bacillus subtilis, and for the
      transition in and out of stationary phase in Escherichia coli. In eukaryotes, the
      same proteases are found in organelles, where they also play important roles.

PMID- 14570583
TI  - Nodal signaling in vertebrate development.
AB  - TGFss signals belonging to the Nodal family set up the embryonic axes, induce
      mesoderm and endoderm, pattern the nervous system, and determine left-right
      asymmetry in vertebrates. Nodal signaling activates a canonical TGFss pathway
      involving activin receptors, Smad2 transcription factors, and FoxH1 coactivators.
      In addition, Nodal signaling is dependent on coreceptors of the EGF-CFC family
      and antagonized by the Lefty and Cerberus families of secreted factors.
      Additional modulators of Nodal signaling include convertases that regulate the
      generation of the mature signal, and factors such as Arkadia and DRAP1 that
      regulate the cellular responses to the signal. Complex regulatory cascades and
      autoregulatory loops coordinate Nodal signaling during early development. Nodals
      have concentration-dependent roles and can act both locally and at a distance.
      These studies demonstrate that Nodal signaling is modulated at almost every level
      to precisely orchestrate tissue patterning during vertebrate embryogenesis.

PMID- 14570584
TI  - Branching morphogenesis of the Drosophila tracheal system.
AB  - Many organs including the mammalian lung and vascular system consist of branched
      tubular networks that transport essential gases or fluids, but the genetic
      programs that control the development of these complex three-dimensional
      structures are not well understood. The Drosophila melanogaster tracheal
      (respiratory) system is a network of interconnected epithelial tubes that
      transports oxygen and other gases in the body and provides a paradigm of
      branching morphogenesis. It develops by sequential sprouting of primary,
      secondary, and terminal branches from an epithelial sac of approximately 80 cells
      in each body segment of the embryo. Mapping of the cell movements and shape
      changes during the sprouting process has revealed that distinct mechanisms of
      epithelial migration and tube formation are used at each stage of branching.
      Genetic dissection of the process has identified a general program in which a
      fibroblast growth factor (FGF) and fibroblast growth factor receptor (FGFR) are
      used repeatedly to control branch budding and outgrowth. At each stage of
      branching, the mechanisms controlling FGF expression and the downstream signal
      transduction pathway change, altering the pattern and structure of the branches
      that form. During terminal branching, FGF expression is regulated by hypoxia,
      ensuring that tracheal structure matches cellular oxygen need. A branch
      diversification program operates in parallel to the general budding program:
      Regional signals locally modify the general program, conferring specific
      structural features and other properties on individual branches, such as their
      substrate outgrowth preferences, differences in tube size and shape, and the
      ability to fuse to other branches to interconnect the network.

PMID- 14570585
TI  - Quality control and protein folding in the secretory pathway.
AB  - The biosynthesis of secretory and membrane proteins in the endoplasmic reticulum
      (ER) yields mostly properly folded and assembled structures with full biological
      activity. Such fidelity is maintained by quality control (QC) mechanisms that
      avoid the production of nonnative structures. QC relies on chaperone systems in
      the ER that monitor and assist in the folding process. When folding promotion is
      not sufficient, proteins are retained in the ER and eventually retranslocated to
      the cytosol for degradation by the ubiquitin proteasome pathway. Retention of
      proteins that fail QC can sometimes occur beyond the ER, and degradation can take
      place in lysosomes. Several diseases are associated with proteins that do not
      pass QC, fail to be degraded efficiently, and accumulate as aggregates. In other
      cases, pathology arises from the downregulation of mutated but potentially
      functional proteins that are retained and degraded by the QC system.

PMID- 14570586
TI  - Adhesion-dependent cell mechanosensitivity.
AB  - The conversion of physical signals, such as contractile forces or external
      mechanical perturbations, into chemical signaling events is a fundamental
      cellular process that occurs at cell-extracellular matrix contacts, known as
      focal adhesions. At these sites, transmembrane integrin receptors are associated
      via their cytoplasmic domains with the actin cytoskeleton. This interaction with
      actin is mediated by a submembrane plaque, consisting of numerous cytoskeletal
      and signaling molecules. Application of intrinsic or external forces to these
      structures dramatically affects their assembly and triggers adhesion-mediated
      signaling. In this review, we discuss the structure-function relationships of
      focal adhesions and the possible mode of action of the putative mechanosensor
      associated with them. We also discuss the general phenomenon of
      mechanosensitivity, and the approaches used to measure local forces at adhesion
      sites, the cytoskeleton-mediated regulation of local contractility, and the
      nature of the signaling networks that both affect contractility and are affected
      by it.

PMID- 14570587
TI  - Plasma membrane disruption: repair, prevention, adaptation.
AB  - Many metazoan cells inhabit mechanically stressful environments and,
      consequently, their plasma membranes are frequently disrupted. Survival requires
      that the cell rapidly repair or reseal the disruption. Rapid resealing is an
      active and complex structural modification that employs endomembrane as its
      primary building block, and cytoskeletal and membrane fusion proteins as its
      catalysts. Endomembrane is delivered to the damaged plasma membrane through
      exocytosis, a ubiquitous Ca2+-triggered response to disruption. Tissue and cell
      level architecture prevent disruptions from occurring, either by shielding cells
      from damaging levels of force, or, when this is not possible, by promoting safe
      force transmission through the plasma membrane via protein-based cables and
      linkages. Prevention of disruption also can be a dynamic cell or tissue level
      adaptation triggered when a damaging level of mechanical stress is imposed.
      Disease results from failure of either the preventive or resealing mechanisms.

PMID- 14570588
TI  - Human scavenger receptor class B type II (SR-BII) and cellular cholesterol
      efflux.
AB  - Although studies in recombinant cells indicate that scavenger receptor class B,
      type I (SR-BI) can promote cholesterol efflux, investigations in transgenic mice
      overexpressing or deficient in SR-BI endorse its physiological function as
      selectively sequestering cholesteryl esters from high-density lipoproteins
      (HDLs). Less clear is the role of SR-BII, a splice variant of the SR-B gene that
      differs only in the C-terminal cytoplasmic domain. Here, we identify several
      putative signalling motifs in the C-terminus of human SR-BII, which are absent
      from SR-BI, and hypothesize that these motifs interact with signalling molecules
      to mobilize stored cholesteryl esters and/or promote the efflux of intracellular
      free cholesterol. 'Pull-down' assays using a panel of tagged SH3 (Src homology 3)
      domains showed that cytoplasmic SR-BII, but not cytoplasmic SR-BI, bound the SH3
      domain of phospholipase C-gamma1; this interaction was not, however, detected
      under more physiological conditions. Specific anti-peptide antisera identified SR
      BII in human monocyte/macrophage THP-1 cells and, in recombinant cells, revealed
      receptor localization to caveolae, a plasma membrane microdomain that
      concentrates signal-transducer molecules and acts as a conduit for cholesterol
      flux between cells and lipoproteins. Consistent with its caveolar localization,
      expression of human SR-BII in recombinant Chinese hamster ovary cells (CHO-SR
      BII) was associated with increased HDL-mediated cholesterol efflux. Nevertheless,
      when CHO-SR-BII cells were pre-loaded with cholesteryl [(3)H]oleate and incubated
      with HDL, cholesteryl ester stores were not reduced compared with control cells.
      We conclude that although human SR-BII is expressed by macrophages, contains
      cytoplasmic signalling motifs and localizes to caveolae, its ability to stimulate
      cholesterol efflux does not reflect enhanced hydrolysis of stored cholesteryl
      esters.

PMID- 14570589
TI  - Sex steroid receptors in rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a disease characterized primarily by chronic
      inflammatory synovitis and is well-known to be associated with significant sex
      differences in its prevalence and clinical features. Sex steroids have been
      proposed to be involved in the pathogenesis of RA, but details pertaining to the
      expression of sex steroid receptors in RA synovial tissue have yet to be fully
      characterized. In the present study, we examined oestrogen receptor (ER) alpha,
      ERbeta, progesterone receptor (PR) and androgen receptor (AR) mRNA expression
      using real-time reverse transcriptase-PCR (RT-PCR) in eight female RA synovial
      tissues and six female synovial tissues without inflammation, and determined
      immunolocalization of ERalpha, ERbeta, PR-A, PR-B and AR using
      immunohistochemistry in synovial tissues obtained from 22 RA patients. Real-time
      RT-PCR analysis demonstrated the expression of ER, PR and AR mRNAs in both RA and
      non-inflamed synovial tissues. Relative abundance of ER mRNAs was significantly
      higher in RA synovial tissue than non-inflamed synovial tissue (P<0.05). In
      addition, the relative ERalpha/ERbeta mRNA expression ratio was significantly
      lower in RA than non-inflamed synovial tissue (RA, 2.34 +/- 1.60; and non
      inflamed, 20.7 +/- 19.1; P<0.05). There were no significant differences in
      relative abundance of PR mRNA. Relative abundance of AR mRNA was significantly
      lower in RA (P<0.05). Immunoreactivity for ERalpha, ERbeta, PR-B and AR was
      detected in the lining cells, inflammatory cells and fibroblasts in all the
      patients examined. The labelling indices for ERbeta and PR-B were more abundant
      in both lining cells (ERbeta, 54.2 +/- 12.2%; PR-B, 73.6 +/- 18.9%) and
      inflammatory cells (ERbeta, 74.6 +/- 16.2%; PR-B, 75.9 +/- 16.1%) than in
      fibroblasts (ERbeta, 36.5 +/- 15.6%; PR-B, 49.4 +/- 18.0%). Labelling indices for
      ERalpha and AR were significantly higher in lining cells (ERalpha, 14.4 +/- 8.6%;
      AR, 31.2 +/- 11.3%) and fibroblasts (ERalpha, 12.1 +/- 7.5%; AR, 20.1 +/- 9.6%)
      than those in inflammatory cells (ERalpha, 5.7 +/- 3.3%; AR, 9.2 +/- 4.4%). There
      were significant differences (P<0.05) in the labelling indices for ERalpha,
      ERbeta and PR-B between men and women under 50 years of age in fibroblasts of RA
      synovial tissues. These results indicate that sex steroid receptors are present
      in RA and non-inflamed synovial tissues, including inflammatory cells in RA, and
      suggest that sex steroids may play important roles in the regulation of
      inflammation of RA synovial tissue.

PMID- 14570590
TI  - Emerging and diverse roles of protein kinase C in immune cell signalling.
AB  - Members of the protein kinase C (PKC) family are expressed in many different cell
      types, where they are known to regulate a wide variety of cellular processes that
      impact on cell growth and differentiation, cytoskeletal remodelling and gene
      expression in the response to diverse stimuli. The broad tissue distribution and
      redundancy of in vitro function have often hampered the identification of
      definitive roles for each PKC family member. However, recent in vivo studies of
      PKC isoenzyme-selective knockout and transgenic mice have highlighted distinct
      functions of individual PKCs in the immune system. These genetic analyses, along
      with biochemical studies utilizing PKC isoenzyme-specific cDNA (wild-type,
      constitutively active and dominant-negative), antisense oligonucleotides (ASO),
      RNA interference (RNAi), and pharmacological inhibitors, indicate that PKC
      regulated signalling pathways play a significant role in many aspects of immune
      responses, from development, differentiation, activation and survival of
      lymphocytes to macrophage activation. The importance of PKCs in cellular immune
      responses suggests that improved understanding of the molecular events that
      govern their actions could point to new avenues for development of treatments for
      immune disorders.

PMID- 14570591
TI  - LEA (late embryonic abundant)-like protein Hsp 12 (heat-shock protein 12) is
      present in the cell wall and enhances the barotolerance of the yeast
      Saccharomyces cerevisiae.
AB  - Yeast cells Saccharomyces cerevisiae, late embryogenic abundant-like stress
      response protein Hsp 12 (heat-shock protein 12) were found by immunocytochemistry
      to be located both in the cytoplasm and in the cell wall, from where they could
      be extracted with dilute NaOH solutions. Yeast cells with the Hsp 12 gene
      disrupted were unable to grow in the presence of either 12 mM caffeine or 0.43 mM
      Congo Red, molecules known to affect cell-wall integrity. The volume of yeast
      cells were less affected by rapid changes in the osmolality of the growth medium
      when compared with the wild-type yeast cells, suggesting a role for Hsp 12 in the
      flexibility of the cell wall. This was also suggested by subjecting the yeast
      cells to rapid changes in barometric pressure where it was found that wild-type
      yeast cells were more resistant to cellular breakage.

PMID- 14570592
TI  - Further evidence that the tyrosine phosphorylation of glycogen synthase kinase-3
      (GSK3) in mammalian cells is an autophosphorylation event.
AB  - Phosphorylation of the endogenous GSK3alpha (glycogen synthase kinase-3alpha) at
      Tyr279 and GSK3beta at Tyr216 was suppressed in HEK-293 or SH-SY5Y cells by
      incubation with pharmacological inhibitors of GSK3, but not by an Src-family
      inhibitor, 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4- d ]pyrimidine
      (PP2), or a general protein tyrosine kinase inhibitor (genistein). GSK3beta
      transfected into HEK-293 cells or Escherichia coli became phosphorylated at
      Tyr216, but catalytically inactive mutants did not. GSK3beta expressed in insect
      Sf 21 cells or E. coli was extensively phosphorylated at Tyr216, but the few
      molecules lacking phosphate at this position could autophosphorylate at Tyr216 in
      vitro after incubation with MgATP. The rate of autophosphorylation was unaffected
      by dilution and was suppressed by the GSK3 inhibitor kenpaullone. Wild-type
      GSK3beta was unable to catalyse the tyrosine phosphorylation of catalytically
      inactive GSK3beta lacking phosphate at Tyr216. Our results indicate that the
      tyrosine phosphorylation of GSK3 is an intramolecular autophosphorylation event
      in the cells that we have studied and that this modification enhances the
      stability of the enzyme.

PMID- 14570594
TI  - Utilization of the propensity score method: an exploratory comparison of proxy
      completed to self-completed responses in the Medicare Health Outcomes Survey.
AB  - BACKGROUND: This research examined the use of the propensity score method to
      compare proxy-completed responses to self-completed responses in the first three
      baseline cohorts of the Medicare Health Outcomes Survey, administered in 1998,
      1999, and 2000, respectively. A proxy is someone other than the respondent who
      completes the survey for the respondent. METHODS: The propensity score method of
      matched sampling was used to compare proxy and self-completed responses. A
      propensity score is a value that equals the estimated probability of a given
      individual belonging to a treatment group given the observed background
      characteristics of that individual. Proxy and self-completed responses were
      compared on demographics, the SF-36, chronic conditions, activities of daily
      living, and depression-screening questions. For each individual survey
      respondent, logistic regression was used to calculate the probability that this
      individual belonged to the proxy respondent group (propensity score). Pre and
      post adjustment comparisons were tested by calculating effect sizes. RESULTS:
      Differences between self and proxy-completed responses were substantially reduced
      with the use of the propensity score method. However, differences were still
      found in the SF-36, several demographics, several impaired activities of daily
      living, several chronic conditions, and one depression-screening question.
      CONCLUSION: The propensity score method helped to reduce differences between
      proxy-completed and self-completed survey responses, thereby providing an
      approximation to a randomized controlled experiment of proxy-completed versus
      self-completed survey responses.

PMID- 14570593
TI  - Transcriptional activation of the murine Muc5ac mucin gene in epithelial cancer
      cells by TGF-beta/Smad4 signalling pathway is potentiated by Sp1.
AB  - The nucleotide sequence of the pMS1 clone was submitted to the GenBank Nucleotide
      Sequence Database under accession number AF288076. Changes in the expression of
      mucin genes in gastrointestinal cancers is thought to contribute to the
      development of the disease. In our laboratory we have shown previously that
      MUC5AC is aberrantly expressed in rectosigmoid villous adenomas. However, the
      regulatory mechanisms underlying that altered profile of expression is unknown.
      In order to study its regulation at the transcriptional level, we have isolated
      and characterized 5.5 kb of the 5'-flanking region of the mouse Muc5ac mucin
      gene. The promoter is flanked by a TATA box and a transcriptional start site is
      located 22 bp downstream of the TATA box. Analysis of the sequence showed a high
      density of binding sites for Smad4, an essential factor in the signalling cascade
      activated by TGF-beta (transforming growth factor-beta), and Sp1, an important
      factor in the regulation of MUC5AC. This led us to study Muc5ac regulation by TGF
      beta. We show that exogenous addition of TGF-beta to the cells induces Muc5ac
      endogenous expression, promoter activity and Smad4 binding to the promoter. By co
      transfection studies we show that Smad4 is essential for Muc5ac promoter
      activation and that it does not synergize with Smad2 or Smad3. By gel-retardation
      and co-transfection assays, we identified Sp1 and Sp3 as important regulators of
      Muc5ac expression and showed that Smad4 and Sp1 act in a co-operative manner to
      transactivate Muc5ac promoter activity. Altogether these results bring new
      insights into the molecular mechanisms of TGF-beta-mediated up-regulation of
      Muc5ac and enhance our understanding as to how Muc5ac is regulated in certain
      pathologies of the gastrointestinal tract.

PMID- 14570597
TI  - Predictors of left atrial appendage stunning after electrical cardioversion of
      non-valvular atrial fibrillation.
AB  - OBJECTIVE: To identify predictors of left atrial appendage stunning after the use
      of electrical cardioversion to restore sinus rhythm in patients with non-valvular
      atrial fibrillation. METHODS: A total of 68 consecutive patients (45 men, 23
      women, 60.5 +/- 8.7 years of age) with non-valvular atrial fibrillation
      undergoing electrical cardioversion were enlisted in this study. Clinical and
      echocardiographic variables were analyzed by univariate regression and
      multivariate logistic regression to investigate the relationship between
      occurrences of left atrial appendage stunning and these factors. RESULTS:
      Univariate analysis revealed that, in comparing patients without and with left
      atrial appendage stunning, there were significant differences in the duration of
      atrial fibrillation > 8 weeks (32.3% vs 75.5%, P < 0.001), left atrial diameter >
      50 mm (29.0% vs 54.1%, P < 0.05), left atrial emptying fraction (31.5% +/- 7.8%
      vs 27.1% +/- 8.5%, P < 0.05), left ventricular ejection fraction < 50% (38.7% vs
      67.6%, P < 0.05), maximum electrical energy (96.8 J +/- 65.8 J vs 156.8 J +/-
      100.8 J, P < 0.01), cumulative electrical energy 146.8 J +/- 142.6 J vs 290.5 J
      +/- 242.1 J, P < 0.01) and number of electrical cardioversion shocks (1.7 +/- 0.9
      vs 2.43 +/- 1.20, P < 0.05). However, backward stepwise multivariate logistic
      regression analysis identified as significant and independent predictors of left
      atrial appendage stunning only duration of atrial fibrillation > 8 weeks (OR =
      7.249, 95% CI = 1.998 - 26.304, P < 0.01), left atrial diameter > 50 mm (OR =
      3.896, 95% CI = 1.105 - 13.734, P < 0.05), left ventricular ejection fraction <
      50% (OR = 4.465, 95% CI = 1.51713.140, P < 0.01) and cumulative energy of
      electrical cardioversion (OR = 1.004, 95% CI = 1.000 - 1.008, P < 0.05).
      CONCLUSIONS: Duration of atrial fibrillation > 8 weeks, left atrial diameter > 50
      mm, left ventricular ejection fraction < 50%, and cumulative energy of electrical
      cardioversion are independent predictors of left atrial appendage stunning.
      Anticoagulation treatment should be individualized for patients undergoing
      electrical cardioversion to reduce the risk of both cardioversion-related
      thromboembolic events and hemorrhagic complications caused by warfarin treatment.

PMID- 14570598
TI  - Effects of renal artery stenting on renal function and blood pressure in patients
      with atherosclerotic renovascular disease.
AB  - OBJECTIVE: To study the effects of percutaneous renal artery intervention on
      renal function and blood pressure in patients with renal artery stenosis.
      METHODS: Eighty-seven patients with severe uni- or bi-lateral renal artery
      stenosis (luminal diameter narrowing >/= 70%) and clinical hypertension received
      renal artery stenting between January 2002 and December 2002. The changes in
      blood pressure and serum creatinine level and creatinine clearance (CCr) 48 hours
      after intervention and during 6 months of follow-up were assessed. RESULTS: Renal
      stenting was performed in 98 stenotic arteries of 87 patients, and the procedural
      success rate was 100%. Serum creatinine level was slightly elevated from (176 +/-
      21) micro mol/L to (179 +/- 11) micro mol/L (P = 0.15) 48 hours after the
      procedure, but significantly decreased to (149 +/- 15) micro mol/L at 6 months (P
      < 0.001). CCr was also greatly improved [(37 +/- 11) ml/min before versus (51 +/-
      8) ml/min at 6 months, P < 0.001]. During follow-up, 61% of the patients
      experienced a normal renal function. Despite conventional medical treatment,
      systolic and diastolic blood pressures were also significantly decreased after
      stenting [(163 +/- 23)/(96 +/- 13) mm Hg before versus (148 +/- 12)/(79 +/- 15)
      mm Hg at 6 months, all P < 0.001], and hypertension was well controlled in 67% of
      the patients at 6 months' follow-up. CONCLUSION: Renal artery stenting has a high
      success rate and is effective in improving renal function and blood pressure for
      patients with severe renal artery stenosis.

PMID- 14570595
TI  - Outcomes and quality of life following breast cancer treatment in older women:
      when, why, how much, and what do women want?
AB  - BACKGROUND: There are few comprehensive reviews of breast cancer outcomes in
      older women. We synthesize data to describe key findings and gaps in knowledge
      about the outcomes of breast cancer in this population. METHODS: We reviewed
      research published between 1995 and June 2003 on breast cancer quality of life
      and outcomes among women aged 65 and older treated for breast cancer. Outcomes
      included communication, satisfaction, and multiple quality of life domains.
      RESULTS: Few randomized trials or cohort studies that measured quality of life
      after treatment focused exclusively on older women. Studies from older women
      generally noted that, with the exception of axillary dissection, type of surgical
      treatment generally had no effect on long-term outcomes. In contrast, the
      processes of care, such as choosing therapy, good patient-physician
      communication, receiving treatment concordant with preferences about body image,
      and low perceptions of bias, were associated with better quality of life and
      satisfaction. CONCLUSIONS: With the exception of axillary dissection, the
      processes of care, and not the therapy itself, seem to be the most important
      determinants of long-term quality of life in older women.

PMID- 14570596
TI  - Ameliorating effect of microdoses of a potentized homeopathic drug, Arsenicum
      Album, on arsenic-induced toxicity in mice.
AB  - BACKGROUND: Arsenic in groundwater and its accumulation in plants and animals
      have assumed a menacing proportion in a large part of West Bengal, India and
      adjoining areas of Bangladesh. Because of the tremendous magnitude of the
      problem, there seems to be no way to tackle the problem overnight. Efforts to
      provide arsenic free water to the millions of people living in these dreaded
      zones are being made, but are awfully inadequate. In our quest for finding out an
      easy, safe and affordable means to combat this problem, a homeopathic drug,
      Arsenicum Album-30, appears to yield promising results in mice. The relative
      efficacies of two micro doses of this drug, namely, Arsenicum Album-30 and
      Arsenicum Album-200, in combating arsenic toxicity have been determined in the
      present study on the basis of some accepted biochemical protocols. METHODS: Mice
      were divided into different sets of control (both positive and negative) and
      treated series (As-intoxicated, As-intoxicated plus drug-fed). Alanine amino
      transferase (ALT) and aspartate amino transferase (AST) activities and reduced
      glutathione (GSH) level in liver and blood were analyzed in the different series
      of mice at six different fixation intervals. RESULTS: Both Arsenicum Album-30 and
      Arsenicum Album-200 ameliorated arsenic-induced toxicity to a considerable extent
      as compared to various controls. CONCLUSIONS: The results lend further support to
      our earlier views that microdoses of potentized Arsenicum Album are capable of
      combating arsenic intoxication in mice, and thus are strong candidates for
      possible use in human subjects in arsenic contaminated areas under medical
      supervision.

PMID- 14570599
TI  - Unipolar electrogram in identification of successful targets for radiofrequency
      catheter ablation of focal atrial tachycardia.
AB  - OBJECTIVE: To analyze the unipolar electrogram from successful and unsuccessful
      ablation sites of focal atrial tachycardia (AT), and to evaluate its value in the
      identification of successful targets. METHODS: Fifteen consecutive patients with
      focal AT were referred for radiofrequency catheter ablation (RFCA). Both unipolar
      (from the tip electrode of ablating catheter) and bipolar (from the distal pair
      of electrode of ablating catheter) electrograms were used to identify the
      ablation targets of focal AT. RESULTS: Successful ablation was echieved in 14
      patients. Radiofrequency energy was delivered at a total of 27 sites. The bipolar
      electrograms associated with successful ablation sites showed earlier atrial
      deflection relative to P wave onset (36 ms +/- 15 ms vs 30 ms +/- 11 ms, P <
      0.05) than the electrograms associated with failed ablation sites. At the 14
      successful ablation sites, the unipolar electrograms displayed a completely
      negative atrial wave ("QS" morphology) beginning with intrinsic deflection.
      However, at the 13 unsuccessful ablation sites, a "rS" morphology of atrial wave
      was shown on the unipolar electrogram. CONCLUSION: The "QS" morphology of the
      atrial wave on unipolar electrograms appears to represent a reliable marker for
      identifying the successful ablation targets of focal AT, with a high sensitivity
      and specificity.

PMID- 14570600
TI  - Effects of catecholamine-beta-adrenoceptor-cAMP system on severe patients with
      heart failure.
AB  - OBJECTIVE: To investigate the association between catecholamine-beta-adrenoceptor
      (beta-AR)-adenosine 3', 5'-monophosphate (cAMP) system and long-term prognosis in
      patients with chronic heart failure (CHF). METHODS: The study population
      comprised 73 patients with CHF (EF: 23% +/- 10%) with a mean follow-up of 3.8 +/-
      1.9 years. Plasma levels of norepinephrine (NE) were measured using high
      performance lipid chromatography, beta-adrenergic receptor density (Bmax) and the
      content of cAMP in peripheral lymphocytes were calculated using 3H
      dihydroalpneolo as ligand and competitive immunoassay, respectively. Deaths due
      to cardiovascular events within the follow-up period were registered. RESULTS:
      The total mortality was 64.7%, 57.4% of which was for cardiogenic (worsening
      heart failure: 32.4%; sudden death: 25.0%). In the cardiogenic death group,
      plasma levels of NE and epinephrine (E) (3.74 nmol/L +/- 0.09 nmol/L and 3.17
      nmol/L +/- 1.0 nmol/L) and the contents of peripheral lymphocyte cAMP (3.64
      pmol/mg protein +/- 1.4 pmol/mg protein) were significantly increased as compared
      with the survival group (2.68 nmol/L +/- 0.07 nmol/L, 2.41 nmol/L +/- 0.24 nmol/L
      and 2.73 pmol/mg protein +/- 0.9 pmol/mg protein, respectively, all P < 0.01). In
      the sudden death group, plasma levels of NE and E (5.01 nmol/L +/- 0.06 nmol/L
      and 4.13 nmol/L +/- 0.08 nmol/L) were significantly increased as compared with
      the worsening heart failure group (2.49 nmol/L +/- 0.07 nmol/L and 2.33 nmol/L +/
      0.8 nmol/L, all P < 0.001) and to the survival group (2.68 nmol/L +/- 0.07
      nmol/L and 2.41 nmol/L +/- 0.14 nmol/L, all P < 0.01). The incidences of sudden
      death were 0%, 75%, and 100% (chi(2) = 16.018, P < 0.01) in patients with plasma
      NE < 2.5 nmol/L, NE 2.5 nmol/L - 4.5 nmol/L, and NE > 4.5 nmol/L, respectively.
      In the worsening heart failure group, the content of peripheral lymphocyte cAMP
      (4.46 pmol/mg protein +/- 0.18 pmol/mg protein) was significantly increased
      compared with the sudden death group (2.39 pmol/mg protein +/- 0.9 pmol/mg
      protein, P < 0.001) and to the survival group (2.73 pmol/mg protein +/- 1.1
      pmol/mg protein, P < 0.001). The worsening heart failure death occurences were
      5.0%, 72.2%, and 100% (chi(2) = 14.26, P < 0.01) in patients with a content of
      peripheral lymphocyte cAMP < 2.5 nmol/L, cAMP 2.5 nmol/L - 4.5 nmol/L, and cAMP >
      4.5 nmol/L, respectively. Bmax in peripheral lymphocyte was not significantly
      different (P > 0.05) among the sudden death, worsening heart failure, and
      survival groups in CHF patients. CONCLUSIONS: Plasma levels of catecholamine
      increase significantly, and Bmax and the contents of cAMP in peripheral
      lymphocytes decrease significantly in patients with CHF. High plasma
      catecholamine levels may be associated with sudden death, and high
      intralymphocyte cAMP content may be associated with worsening heart failure in
      CHF patients.

PMID- 14570602
TI  - Expression of telomerase hTERT in human non-small cell lung cancer and its
      correlation with c-myc gene.
AB  - OBJECTIVE: To investigate the expression of human telomerase catalytic subunit,
      hTERT, in human non-small cell lung cancer (NSCLC) and its correlations to c-myc
      gene. METHODS: hTERT and c-myc mRNA expressions were detected by semiquantitative
      reverse transcription-polymerase chain reaction (RT-PCR). Statistical correlation
      analysis was made to estimate whether there was interrelation between them.
      RESULTS: Positive rate of hTERT expression in 51 surgically resected lung cancer
      specimens was 86.3%, significantly higher than that in adjacent non-neoplastic
      lung tissues and benign lesions, which were 14.3% and 27.3% respectively. No
      statistical significance was observed between the frequency of hTERT expression
      and histologic types, degree of differentiation, TNM stages, tumor size or lymph
      nodes metastases. Correlation analysis revealed that the expression of c-myc gene
      was significantly related to that of hTERT (correlation coefficient, r = 0.633, P
      < 0.001). CONCLUSIONS: hTERT may be a useful tumor marker in diagnosing lung
      cancer. Significant correlation between the expression of hTERT and c-myc mRNA
      indicates that the activation and up-regulation of hTERT might be conferred by
      over-expression of c-myc gene.

PMID- 14570601
TI  - Clinical diagnostic approach to severe acute respiratory syndrome: an
      institution's experience.
AB  - OBJECTIVE: To analyze diagnostic approach to severe acute respiratory syndrome
      (SARS) according to the diagnostic criteria issued by the Ministry of Health of
      China (MHC). METHODS: The clinical data and the diagnostic results of 108 cases
      of SARS were retrospectively reviewed according to the MHC criteria. RESULTS:
      There were 55 men and 53 women, with a median age of 34.5 years (range, 12 - 78
      years). The interval between their first visit and clinical diagnosis was 3 days
      (range, 0 - 14 days). The diagnosis was made at the first visit in 7 (6.5%,
      7/108) cases with a history of exposure to SARS patients and infiltrates on chest
      radiograph. Eighty-nine (82.4%) and 12 (11.1%) patients were categorized as
      probable cases and suspected cases respectively at their first visit and a
      clinical diagnosis of SARS was made subsequently. The interval between first
      visit and reaching the final diagnosis was 1 - 3 days in 72 (66.7%) cases and 4
      days in 29 (26.9%) cases. The final diagnosis was made in 0 - 14 days (median, 2
      days) for those (n = 59, 54.6%) with a history of close contact with SARS
      patients and 2 - 8 days (median, 3 days) for those (n = 49, 45.4%) living in
      Beijing but without such a history (P = 0.03). The chest radiograph was
      interpreted as unremarkable in 26 (24.1%) cases at their first visit, and the
      diagnosis was made in 4 days (range 2 - 8 days), which was significantly longer
      compared with other cases (P < 0.001). In patients without a history of close
      contact with SARS patients, all the five criteria were met after combination
      antibiotic therapy had failed. CONCLUSIONS: A chest radiograph without
      infiltrates at the early stage of SARS is an important factor responsible for
      delayed diagnosis. In patients without a history of close contact with SARS
      cases, antibiotic effect was a major factor influencing doctors' diagnosis.

PMID- 14570603
TI  - Metabolic effects of a novel bioartificial liver on serum from severe hepatitis
      patients: an in vitro study.
AB  - OBJECTIVE: To establish a novel bioartificial liver (BAL) consisting of spheroids
      of porcine hepatocytes in a hollow-fiber bioreactor, and to perform an in vitro
      study on its metabolic effects on the serum from severe hepatitis B patients.
      METHODS: Hepatocytes were isolated from pup pigs and cultured as aggregate
      spheroids through rotation and vibration. Phase-contrast microscopy, transmission
      electron microscopy, and scanning electron microscopy were used for morphological
      detection of hepatocyte spheroids. The hepatocyte spheroids were then transferred
      into the shell of a polysulfone hollow-fiber bioreactor, creating a novel BAL.
      Diluted serum samples of severe hepatitis B patients were circulated for 3 hours
      each into the bioreactor, by using an extracorporeal circulatory system. Every
      half hour, including both before and after perfusion, serum samples were
      collected to assay total bilirubin (TBIL), total protein (TP), albumin (ALB), and
      globulin (GLB) concentrations in order to judge the metabolic effects of this
      novel BAL. RESULTS: Most hepatocytes had formed spheroids with high viability
      after 24 hours in culture. After 3 hours of perfusion, when compared with the
      control group, the serum concentration of TBIL in the treatment group decreased
      significantly (P < 0.01), but the serum concentrations of TP and ALB increased
      significantly (P < 0.05). CONCLUSIONS: Hepatocytes can be conveniently cultured
      as aggregate spheroids through a rotation and vibration method. The novel BAL is
      efficient in removing bilirubin from the serum of severe hepatitis B patients,
      and in supplying the serum with ALB. Thus, the BAL might provide effective
      therapy for patients with severe hepatitis B.

PMID- 14570604
TI  - Antitumor effects of interleukin-18 gene-modified hepatocyte cell line on
      implanted liver carcinoma.
AB  - OBJECTIVE: To investigate the antitumor effects of intrasplenically transplanted
      interleukin-18 (IL-18) gene-modified hepatocytes on murine implanted liver
      carcinoma. METHODS: Embryonic murine hepatocyte cell line (BNL-CL2) was
      transfected with a recombinant adenovirus encoding IL-18 and used as delivery
      cells for IL-18 gene transfer. Two cell lines, BNL-LacZ and BNL-CL2, were used as
      controls. One week after intrasplenic injection of C26 cells (colon carcinoma
      line), tumor-bearing syngeneic mice underwent the intrasplenic transplantation of
      IL-18 gene-modified hepatocyte cell line and were divided into treatment group
      (BNL IL-18) and control groups (BNL-LacZ and BNL-CL2). Two weeks later, the serum
      levels of IL-18, interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF
      alpha) and nitric oxide (NO) in the implanted liver carcinoma-bearing mice were
      assayed, the cytotoxicity of murine splenic cytotoxic T-lymphocytes (CTLs) was
      measured, and the morphology of the hepatic tumors was studied to evaluate the
      antitumor effects of the approach. RESULTS: In the treatment group, the serum
      levels of IL-18, IFN-gamma, TNF-alpha and NO increased significantly. The splenic
      CTL activity increased markedly (P < 0.01), accompanied by a substantial decrease
      in tumor volume and the percentage of tumor area and prolonged survival of liver
      carcinomo-being mice. CONCLUSIONS: In vivo IL-18 expression by ex vivo
      manipulated cells with IL-18 recombinant adenovirus is able to exert potent
      antitumor effects by inducing a predominantly T-cell-helper type 1 (Th1) immune
      response. Intrasplenic transplantation of adenovirus-mediated IL-18 gene-modified
      hepatocytes could be used as a targeting treatment for implanted liver carcinoma.

PMID- 14570605
TI  - Image-guided resection of cerebral cavernous malformations.
AB  - OBJECTIVE: To evaluate retrospectively the effectiveness of image-guided
      navigation techniques in the management of cerebral CMs. METHODS: Between July
      1997 and January 2001, 44 patients underwent image-guided resection of cerebral
      CMs. To counteract brain shift, a small silicon catheter was implanted as a guide
      in the case of deep-seated lesions (except in the case of brain stem CMs) and
      before excision of multiple lesions. RESULTS: A total of 27 men and 17 women with
      a mean age of 35 years underwent surgical procedures (5 patients had multiple
      lesions). The lesions were located in the frontal (n = 14), lobe temporal lobe (n
      = 12), parietal lobe (n = 6), cerebellum (n = 6), thalamus (n = 5), pons (n = 5),
      and orbital region (n = 1). Under the guidance of a StealthStation navigator,
      total removal of the lesions was achieved in all patients. Follow-up revealed
      marked improvement of preoperative symptoms in 26 patients and no additional
      deficits in 13 patients. Five patients suffered from additional neurological
      deficits, but two of them gradually improved during the follow-up period.
      CONCLUSIONS: With the assistance of an image-guided surgical system, functional
      areas can be effectively avoided and surgical injury can be decreased. This
      system is well suited for accurate localization and safe resection of small, deep
      seated CMs.

PMID- 14570606
TI  - Neuronavigator-guided glioma surgery.
AB  - OBJECTIVE: To evaluate the effectiveness of neuronavigator-guided surgery for the
      resection of gliomas. METHODS: A total of 80 patients with gliomas underwent
      surgical treatment under the StealthStation neuronavigator to estimate the extent
      of the tumors. In 27 cases, the measurements of brain shifts at the dura,
      cortical surface and lesion margin were recorded during the operations. A
      technique termed "micro-catheter fence post" was used in superficial gliomas to
      compensate for brain shift. RESULTS: Mean fiducial error and predicted accuracy
      in the 80 cases were 2.03 mm +/- 0.89 mm and 2.43 mm +/- 0.99 mm, respectively.
      The shifts at the dura, cortical surface and lesion margin were 3.44 mm +/- 2.39
      mm, 7.58 mm +/- 3.75 mm, and 6.55 mm +/- 3.19 mm, respectively. Although
      neuronavigation revealed residual tumors, operations were discontinued in 5 cases
      of deep-seated gliomas. In the other 75 cases, total tumor removals were achieved
      in 62 (82.7%), and subtotal removals were achieved in 13 (17.3%). Post-operation,
      neurological symptoms were improved or unchanged in 68 cases (85.0%), and
      worsened in 12 (15.0%). No deaths occurred during the operations and post
      operations. CONCLUSIONS: Intraoperative brain shifts mainly contribute to the
      fail of spatial accuracy during neuronavigator-guided glioma surgery. The "micro
      catheter fence post" technique used for glioma surgery is shown to be useful for
      compensating for intraoperative brain shifts. This technique, thus, contributes
      to an increase in total tumor removal and a decrease in surgical complications.

PMID- 14570607
TI  - Influence of patients' age on functional recovery after transplantation of
      olfactory ensheathing cells into injured spinal cord injury.
AB  - OBJECTIVE: To evaluate the restoration of function after spinal cord injury (SCI)
      in patients of different ages who have underwent intraspinal transplantation of
      olfactory ensheathing cells (OECs). METHODS: One hundred and seventy-one SCI
      patients were included in this study. Of them, 139 were male and 32 were female,
      with age ranging from 2 to 64 years (mean, 34.9 years). In all SCI patients the
      lesions were injected at the time of operation with OECs. According to their
      ages, the patients were divided into 5 groups: </= 20 years group (n = 9), 21 -
      30 years group (n = 54), 31 - 40 years group (n = 60), 41 - 50 years group (n =
      34) and > 51 years group (n = 14). The spinal cord function was assessed based on
      the American Spinal Injury Association (ASIA) Classification System before and 2 
      8 weeks after OECs transplantation. One-way ANOVA and q test were used for
      statistical analysis, and the data were expressed as mean +/- SD. RESULTS: After
      surgery, the motor scores increased by 5.2 +/- 4.8, 8.6 +/- 8.0, 8.3 +/- 8.8, 5.7
      +/- 7.3 and 8.2 +/- 7.6 in 5 age groups respectively (F = 1.009, P = 0.404);
      light touch scores increased by 13.9 +/- 8.1, 15.5 +/- 14.3, 12.0 +/- 14.4, 14.1
      +/- 18.5 and 24.8 +/- 25.3 respectively (F = 1.837, P = 0.124); and pin prick
      scores increased by 11.1 +/- 7.9, 17.2 +/- 14.3, 13.2 +/- 11.8, 13.6 +/- 13.9 and
      25.4 +/- 24.3 respectively (F = 2.651, P = 0.035). Restoration of pin prick in >
      51 years group was better than other age groups except 21 - 30 years group.
      CONCLUSION: OECs transplantation can improve the neurological function of spinal
      cord of SCI patients regardless of their ages. Further research into the long
      term outcomes of the treatment will be required.

PMID- 14570608
TI  - Relationship between glutamate in the limbic system and hypothalamus-pituitary
      adrenal axis after middle cerebral artery occlusion in rats.
AB  - OBJECTIVE: To investigate the features of glutamate activity in the limbic system
      and the effects of glutamate on the activation of the hypothalamus-pituitary
      adrenal (HPA) axis throughout both acute cerebral ischemia and reperfusion.
      METHODS: The changes in glutamate content in the nervous cell gap, in
      corticotrophin releasing hormone (CHR) mRNA expression level in brain tissue, and
      in adrenocorticotropic hormone in blood plasma at different time-points after
      middle cerebral artery occlusion (MCAO) in rats were determined respectively with
      high-performance liquid chomatography (HPLC) and in situ hybridization. RESULTS:
      Glutamate content in the hippocampus and the hypothalamus increased rapidly at
      ischemia 15 minutes, and reached peak value (the averages were 21.05 mg/g +/-
      2.88 mg/g and 14.20 mg/g +/- 2.58 mg/g, respectively) at 1 hour after middle
      cerebral artery occlusion. During recirculation, it returned rapidly to the
      baseline level. At 24 hours after reperfusion, it went up once more, and remained
      at a relative high level until 48 hours after reperfusion, and then declined
      gradually. CRH mRNA expression levels in the temporal cortex, hippocampus and
      hypothalamus were enhanced markedly at 1 hour ischemia and were maintained until
      96 hours after reperfusion. At the same time, adrenocorticotropic hormone level
      in plasma was relatively increased. In the peak stage of reperfusion injury,
      there was a significantly positive correlation (n = 15, r = 0.566, P < 0.05) of
      the glutamate contents in the hypothalamus with the number of cells positive for
      CRH mRNA expression level in the hypothalamus. CONCLUSION: It is probable that
      the CRH system in the central nervous system is mainly distributed in the limbic
      system, and glutamate might be one of the trigger factors to induce excessive
      stress response in the HPA axis.

PMID- 14570609
TI  - Effects of extracellular signal-regulated kinase (ERK) on focal cerebral
      ischemia.
AB  - OBJECTIVE: To determine the role of extracellular signal-regulated kinase
      (ERK)1/2 during focal cerebral ischemia. METHODS: Left middle cerebral artery
      occlusion (MCAO) was undergone after the introduction of a nylon suture to the
      left internal carotid artery in 70 male adult CD-1 mice. ERK 1/2 phosphorylation
      was detected using Western blot analysis, and the morphological feature was
      determined by immunohistochemistry. An ERK pathway inhibitor, 1,4-diamino-2,3
      dicyano-1,4-bis[2-amino-phenylthio] butadiene (U0126), was administered
      intravenously 20 minutes before MCAO, and the neurological deficit levels and the
      infarct volumes were measured 24 hours after MCAO. RESULTS: Phosphorylated ERK
      1/2 (pERK 1/2) activity increased after 30 minutes of MCAO and peaked at 2 hours.
      The immunohistochemical study displayed a large number of pERK 1/2 positive cells
      in the ischemic basal ganglion and surrounding cortex. Double-labeled fluorescent
      staining identified the pERK1/2 positive cells as neurons or astrocytes. In U0126
      treated mice which had undergone 24 hours of MCAO, the neurological deficit
      levels and the infarct volumes were 44.6% and 45.8% respectively, less than those
      of the control mice. CONCLUSIONS: ERK plays an important role in focal cerebral
      ischemia and inhibition of the ERK pathway can help protect against ischemic
      brain injury, which may provide a therapeutic approach for cerebral ischemia.

PMID- 14570610
TI  - Combination of balanced ultrafiltration with modified ultrafiltration attenuates
      pulmonary injury in patients undergoing open heart surgery.
AB  - OBJECTIVE: To explore the effects of ultrafiltration technique in preventing and
      relieving pulmonary injury in children undergoing open heart surgery and
      cardiopulmonary bypass (CPB). METHODS: Thirty cases with congenital heart defects
      were divided into a control group and an experimental group. In the control
      group, conventional cardiopulmonary bypass was used without ultrafiltration;
      while in the experimental group, cardiopulmonary bypass with balanced
      ultrafiltration and modified ultrafiltration were used. Pulmonary static
      compliance (Cstat), airway resistance (Raw), alveolar-arterial oxygen difference
      (A-a DO2), hematocrit (HCT), serum albumin (Alb), interleukin-6 (IL-6),
      endothelia-1 (ET-1) and thromboxane (TXB2) were measured. RESULTS: The pulmonary
      function was improved, HCT and serum albumin concentrations were increased, and
      some harmful medium-size solutes were decreased in the experimental groups
      compared with the control group. CONCLUSIONS: Combination of balanced
      ultrafiltration with modified ultrafiltration can effectively concentrate blood,
      exclude harmful inflammatory mediators, and attenuate lung edema and inflammatory
      responsive pulmonary injury.

PMID- 14570611
TI  - Influence of bladder outlet obstruction and detrusor contractility on residual
      urine in patients with benign prostatic hyperplasia.
AB  - OBJECTIVE: To study the relationship between the degree of bladder outlet
      obstruction (BOO), detrusor contractility and residual urine in patients
      suffering from benign prostatic hyperplasia (BPH). METHODS: In 181 patients with
      BPH, degree of BOO, detrusor contractility, residual urine caculated from
      cathetering combined with the difference between the filling and the voiding were
      recorded and analysized statistically using urodynamic technique. RESULTS:
      Residual urine increased when the detusor contractility was weakened (F = 12.134,
      P = 0.001). In patients wih severe BOO, there was no significant difference in
      residual urine (F = 2.386, P = 0.071). CONCLUSIONS: Increased residual urine is
      mainly resulted from decreased detrusor contractility. BOO has no significant
      influence on residual urine. Some patients with normal or weakened detrusor
      contractility may have more residual urine.

PMID- 14570612
TI  - Age-dependent changes in beta-adrenoceptor function in human detrusors and
      possible mechanisms.
AB  - OBJECTIVE: To study age-dependent changes in beta-adrenergic responsiveness and
      their possible mechanisms. METHODS: Responsiveness to the beta-adrenergic
      agonists isoprenaline, BRL37344, forskolin, and dibutyryl cyclic AMP (DBcAMP) was
      examined in samples from 10 older patients by using a cellular function test. A
      radioligand binding assay was performed using the non-selective beta-adrenergic
      receptor ligand [3H]-dihydroalprenolol ([3H]-DHA). Specimens from 10 young men
      were used as controls. RESULTS: There were no age-dependent changes in
      contractile response to KCl. The relaxation responses to isoprenaline, BRL37344,
      and forskolin decreased in the aged group by 15.0%, 17.6%, and 12.6%,
      respectively (P < 0.001). The pD2 values for isoprenaline and BRL37344 also
      declined significantly. There was no difference in the responsiveness to
      dibutyryl cyclic AMP (DBcAMP) between the two groups; the maximum binding site
      decreased significantly with increasing age, but the equilibrium-dissociation
      constant did not change. CONCLUSIONS: There is an age-related decline in beta
      adrenergic responsiveness which might be one of the causative factors of reduced
      bladder compliance in the elderly. A decrease in cAMP level caused by reduced
      receptor density and adenylyl cyclase activity might be the underlying molecular
      mechanism of the changes in beta-adrenergic responsiveness.

PMID- 14570613
TI  - Effects of blocking androgen receptor expression with specific hammerhead
      ribozyme on in vitro growth of prostate cancer cell line.
AB  - OBJECTIVE: To study the possibility of gene therapy for prostate cancer by
      blocking androgen receptor (AR) gene expression using a specific hammerhead
      ribozyme (RZ). METHODS: The hammerhead ribozyme expression vector pcDNA-hAR-RZ,
      specific to AR mRNA, was constructed and transfected into the prostate cancer
      cell line LNCaP by using lipofectamine. Androgen receptor expression was measured
      by RT-PCR and immunohistochemical methods. Cellular proliferation activities were
      assayed using the tetrazolium bromide colorimetry method; cell cycle changes were
      observed by flow cytometry; and cell apoptosis was detected by the TdT-mediated
      dUTP-biotin nick end labeling method. RESULTS: One to seven days after
      transfection with the ribozyme expression vector, AR mRNA expression at molecular
      and protein levels in LNCaP cells decreased by 32.6% - 40.7% (P < 0.05) and 21.0%
      - 87.64% (P < 0.05) respectively, and cell proliferation was inhibited by 18.28% 
      35.34% (P < 0.05). Meanwhile, the cell cycle was arrested at the G2/M stage, and
      apoptotic morphological changes occurred with an apoptosis rate of 25.17% (P <
      0.01). CONCLUSION: Ribozyme specific against AR mRNA is capable of inhibiting the
      expression AR and inducing the apoptosis in prostate cancer cells.

PMID- 14570614
TI  - Capitate transposition to replace necrotic lunate bone with a pedicle for
      Kienbock's disease: review of 30 cases.
AB  - OBJECTIVE: To investigate the clinical application of capitate transposition with
      a pedicle in 30 cases of Kienbock's disease. METHODS: The external diameter and
      curvature of the capitate head and proximal facet of the lunate were observed and
      measured in 100 specimens. The vascularity of the capitate was also investigated.
      Capitate transposition with a vascular pedicle was designed to treat 30 patients
      with advanced Kienbock's disease who were followed up for 2 to 16 years and then
      analyzed according to Evans's scoring system. RESULTS: Aseptic necrosis did not
      occur in the transposed capitate because the pedicle fascia including the dorsal
      branch of the anterior interosseous artery ensured the vascularity of proximal
      two thirds of the capitate. The transposed capitate reestablished a relatively
      pain-free radiocarpal joint. Follow-up results showed that grip strength and
      motion arc were up to 70% of contralateral side. CONCLUSIONS: Capitate
      transposition with a pedicle is a reliable treatment method for advanced
      Kienbock's disease, with favorable prognosis for at least five years
      postoperatively.

PMID- 14570615
TI  - Posterior chamber phakic intraocular lens implantation for high myopia.
AB  - OBJECTIVE: To evaluate the efficacy, safety and stability of posterior chamber
      phakic intraocular lens (PIOLs) implantation for the correction of high myopia.
      METHODS: Thirty-nine eyes of twenty patients with high myopia (between -11.75 and
      -25.75 diopters) had a posterior chamber PIOL (Staar ICL) implanted. During 6 -
      48 months' follow-up, visual acuity, refraction, intraocular pressure (IOP),
      corneal reaction and space between crystal lens and intraocular lens (IOLs) were
      tested. RESULTS: Successful implantation was achieved in all patients. Visual
      acuity without correction greater than 0.5 was found in 34 eyes at 1 day and 3
      months postoperatively. Thirty-five eyes maintained a low negative power of
      refraction (-1.42 +/- 1.32 doipters), which did not prevent the patients from
      most of their daily activities. During 3 - 48 months' follow-up, refraction was
      stable and no cornea edema and glaucoma was found. Two eyes of one patient had
      corticosteroid glaucoma and another eye showed cataractogenesis under anterior
      capsular membrane. CONCLUSION: Posterior chamber PIOL implantation is
      predictable, safe, and effective in the correction of high myopia, and its
      indications should be carefully selected.

PMID- 14570616
TI  - Clinical features of pheochromocytoma and perioperative anesthetic management.
AB  - OBJECTIVE: To investigate clinical features of pheochromocytoma and summarize
      experiences of anesthetic management during the perioperative period. METHODS:
      Two hundred and fifty eight patients who were diagnosed with pheochromocytoma in
      our hospital were reviewed retrospectively for clinical features. According to
      different preoperative pharmalogical preparations, perioperative mortalities were
      analyzed in three periods (Period 1: January 1955 - December 1975; Period 2:
      January 1976 - December 1994; Period 3: January 1995 - July 2001). In Period 3,
      hemodynamic changes in the patients undergoing different anesthetic methods were
      analyzed. RESULTS: About 5.8% (15/258) of pheochromocytoma was an integral part
      of multiple endocrine neoplasia (MEN) type II or mixed type. Sixty percent
      (149/249) of the patients who had undergone surgery possessed evidence of
      catecholamine cardiac toxicity preoperatively. Impaired glucose tolerance was
      found in 59% (147/249) of the patients before surgery. Perioperative mortality
      was significantly decreased from 8% (5/60) in Period 1 to 1.2% (1/75) in Period 2
      (P < 0.01). No perioperative deaths occurred in Period 3. The volume infused
      during the operation was significantly higher both in the epidural anesthesia
      group (3474 ml +/- 624 ml, P < 0.01) and in the epidural plus general anesthesia
      group (3654 ml +/- 475 ml, P < 0.01) than in the general anesthesia group (2534
      ml +/- 512 ml). There were favorable hemodynamic characteristics in patients
      before removal of the tumor in the epidural anesthesia group and in the epidural
      plus general anesthesia group, as compared with the general anesthesia group.
      CONCLUSIONS: A positive surgical outcome of the excision of pheochromocytoma
      depends on multiple factors, including careful assessment of potential vital
      organ damage before surgery and restoration of blood volume by establishing alpha
      blockade preoperatively, meticulous anesthetic management of patients during
      surgery, and appropriate circulatory support after surgery.

PMID- 14570617
TI  - Effects of magnesium sulfate on neuron apoptosis and expression of caspase-3, bax
      and bcl-2 after cerebral ischemia-reperfusion injury.
AB  - OBJECTIVE: To investigate the effects of magnesium sulfate on neuron apoptosis
      and the expressions of caspase-3, bax and bcl-2 after cerebral ischemia
      reperfusion injury. METHODS: Thirty-six gerbils were randomly divided into three
      groups: Sham-operation group (So, n = 12), ischemia-reperfusion group (I-R, n =
      12) and magnesium sulfate group (Ms, n = 12). The neuron apoptosis was detected
      by the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-fluorescence
      nick end labeling (TUNEL stain), and the protein expressions of caspase-3, bax
      and bcl-2 were detected by immunohistochemisty stain. RESULTS: Apoptotic neurons
      and the expressions of caspase-3 and bax were significantly increased in I-R and
      Ms groups, compared with those in So group. Apoptotic neurons and the expressions
      of bax and caspase-3 in Ms group were significantly less than those in I-R group.
      There was no significant difference in the expression of bcl-2 among three
      groups. CONCLUSIONS: Magnesium sulfate decreases neuron apoptosis after cerebral
      ischemia-reperfusion injury, which may be related with the suppressed expressions
      of caspase-3 and bax.

PMID- 14570618
TI  - Analysis of low-density lipoprotein receptor gene mutations in a Chinese patient
      with clinically homozygous familial hypercholesterolemia.
AB  - OBJECTIVE: To screen the point mutation of the low-density lipoprotein receptor
      (LDL-R) gene in Chinese familial hypercholesterolemia (FH) patients, characterize
      the relationship between the genotype and the phenotype and discuss the molecular
      pathological mechanism of FH. METHODS: A patient with clinical phenotype of
      homozygous FH and her parents were investigated for mutations in the promoter and
      all eighteen exons of the LDL-R gene. Screening was carried out using Touch-down
      PCR and direct DNA sequencing; multiple alignment analysis by DNASIS 2.5 was used
      to find base alteration, and the LDL-R gene mutation database was searched to
      identify the alteration. In addition, the apolipoprotein B gene (apo B) was
      screened for known mutations (R3500Q) that cause familial defective apo B100
      (FDB) by polymerase chain reaction-restriction fragment length polymorphism (PCR
      RFLP). RESULTS: Two new heterozygous mutations in exons 4 and 9 of the LDL-R gene
      were identified in the proband (C122Y and T383I) as well as her parents. Both of
      the mutations have not been published in the LDL-R gene mutation database. No
      mutation of apo B100 (R3500Q) was observed. CONCLUSION: Two new mutations (C112Y
      and T383I) were found in the LDL-R gene, which may result in FH and may be
      particularly pathogenetic genotypes in Chinese people.

PMID- 14570619
TI  - RHD gene polymorphism among RhD-negative Han Chinese.
AB  - OBJECTIVE: To evaluate the status of eight RHD specific exons in 131 Han Chinese
      blood donors who were classified as RhD-negative by serological methods and
      explore the genomic structure of RHD gene among the Han Chinese. The Rh blood
      group system has the highest prevalence of polymorphisms among human blood group
      systems and is clinically significant in transfusion medicine. The Rh antigens
      are expressed on polypeptides encoded by two highly homologous genes, RHD and
      RHCE. Recent molecular studies have shown that the RhD-negative trait could be
      generated by multiple genetic mechanisms and is ethnic group-dependent. METHODS:
      The polymerase chain reaction using-sequence specific primers (PCR-SSP) was used
      to amplify exons 2, 3, 4, 5, 6, 7, 9 and 10 of RHD gene and exons 1, 2 and 5 of
      RHCE gene, as well as intron 4 in each of them. RESULTS: The 131 cases of RhD
      negative phenotypes consisted of 60 ccee, 58 Ccee, 5 ccEe, 5 CcEe and 3 CCee.
      Among them, 83 with the Rh ccee or ccEe phenotypes (63.4%) lacked the eight RHD
      exons indicated above, while 26 cases with the Rh Ccee, CCee, CcEe phenotypes
      (19.9%) had all the RHD exons examined. Twenty-two individuals with the Ccee,
      CCee, CcEe phenotypes (16.8%) carried at least one RHD exon. The phenotypes of
      the RhD negative individuals carrying the RHD gene were Rh CC or Cc, but not cc.
      CONCLUSIONS: Three classes of RhD-negative polymorphisms among a population of
      Han Chinese were observed. Antigen association analysis suggested the existence
      of a novel class of RhD-negative associated haplotype in Han Chinese. This
      haplotype consisted of a normal RHCE allele and a nonfunctional RHD gene. It may
      be beneficial to redefine the RhD-negative blood group among Chinese populations
      upon clarification of the mechanisms of RHD gene expression and RhD antigen
      immunization.

PMID- 14570620
TI  - Vascular endothelial growth factor gene transfection to enhance the repair of
      avascular necrosis of the femoral head of rabbit.
AB  - OBJECTIVE: To explore a new method for the therapy of avascular necrosis of the
      femoral head. METHODS: The recombinant plasmid pCD-hVEGF165 was mixed with
      collagen and was implanted in the necrotic femoral head. The expression of
      vascular endothelial growth factor (VEGF) was examined by RNA dot hybridization
      and immunohistochemical techniques. Repair of the femoral head was observed by
      histological and histomorphometric analysis. RESULTS: The expression of VEGF was
      detected in the femoral head transfected with the VEGF gene. The femoral head
      transfected with the VEGF gene showed a significant increase in angiogenesis 2
      and 4 weeks after gene transfection and a significant increase in bone formation
      6 and 8 weeks after gene transfection on histomorphometric analysis (P < 0.01).
      CONCLUSIONS: Transfection of the VEGF gene enhances bone tissue angiogenesis.
      Repair of osteonecrosis could be accelerated accordingly, thus providing a
      potential method for therapy of osteonecrosis.

PMID- 14570621
TI  - Increased apoptosis and decreased density of medial smooth muscle cells in human
      abdominal aortic aneurysms.
AB  - OBJECTIVE: To determine the increase of apoptosis and the decrease of smooth
      muscle cells (SMCs) density in human abdominal aortic aneurysms (AAA). METHODS:
      In situ terminal transferase-mediated dUTP nick end labeling (TUNEL) was employed
      to detect apoptosis of SMCs in patients with AAA (n = 25) and normal abdominal
      aortae (n = 10). Positive cells were identified by specific cell marker in
      combination with immunohistochemistry. Meanwhile SMC counting was performed by
      anti-alpha-actin immunohistostaining to compare the SMC density. RESULTS: TUNEL
      staining revealed that there was significantly increased apoptosis in AAAs
      (average 8.6%) compared with normal abdominal aortae (average 0.95%, P < 0.01).
      Double staining showed that most of these cells were SMCs. Counting of alpha
      actin positive SMCs revealed that medial SMC density of AAAs (37.5 +/- 7.6
      SMCs/HPF) was reduced by 79.1% in comparison with that of normal abdominal aortae
      (179.2 +/- 16.1 SMCs/HPF, P < 0.01). CONCLUSIONS: Significantly increased SMCs of
      AAA bear apoptotic markers initiating cell death. Elevated apoptosis may result
      in a decreased density of SMCs in AAA, which may profoundly influence the
      development of AAA.

PMID- 14570622
TI  - Protein kinase C in proliferation and infiltration of eosinophils in nasal polyp.
AB  - OBJECTIVE: To explore the significance of protein kinase C (PKC) in proliferation
      and infiltration of eosinophils in nasal polyps. METHODS: With in situ
      hybridization and immunohistochemistry staining methods, PKC, pro-apoptotic, and
      anti-apoptotic gene (Bax, bcl-2) expressions were measured in nasal polyp tissues
      from 26 patients and inferior turbinate mucosa tissues (ITMTs) from 20 healthy
      persons. The May-Grunwald-Giemsa (MGG) staining method was used to identify
      eosinophils. RESULTS: In eosinophils, the positive cell expressive rates of Bcl-2
      mRNA and its protein were significantly higher in the group with nasal polyps
      than in the ITMT group (P < 0.01). Although the positive cell expressive rate of
      Bax mRNA and associated protein were a little higher in the group with nasal
      polyp tissues than in the ITMT group, the difference was not significant (P >
      0.05). There was PKC expression in the eosinophils of 26 cases of nasal polyps,
      but occasional PKC expression in 7 of 20 ITMT cases. In the two groups, PKC
      positive cell expression was significantly different, and the expression of PKC
      and bcl-2 mRNA as well as associated protein in eosinophils of nasal polyps
      showed a remarkably positive relationship (r1 = 0.0875, r2 = 0.0823, P < 0.01).
      CONCLUSIONS: Increased PKC expression in eosinophils of nasal polyp tissues is
      closely associated with apoptosis inhibition, and it is presumed that eosinophil
      apoptosis inhibition in nasal polyp tissues is obtained by activation of the PKC
      signal transduction pathway.

PMID- 14570623
TI  - HLA-DRB1 allele in 35 patients with alveolar echinococcosis in Gansu Province of
      China.
AB  - OBJECTIVE: To investigate the association between histocompatibility leukocyte
      antigen (HLA)-DRB1 alleles and alveolar echinococcosis (AE). METHODS: Thirty-five
      patients with AE in high prevalence areas in Gansu Province of China were tested
      for the HLA-DRB1 gene using the polymerase chain reaction with sequence-specific
      primer (PCR-SSP) technique. The results were compared with those of 104 healthy
      individuals. RESULTS: The frequency of the HLA-DRB1 * 040x gene was 26% in the
      patient group, which was significantly higher than that in the control group
      (9.62%) with a relative risk (RR) of 4.45 (chi(2) = 13.67, P < 0.01), and an
      etiological fraction (EF) of 0.20. The frequency of the HLA-DRB1 * 0701 allele
      was significantly lower in the patient group (2.86%) as compared to the control
      group (13.94%; chi(2) = 6.67, P < 0.05) with a preventable fraction (PF) of 0.30.
      The frequencies of other DRB1 alleles were not significantly different.
      CONCLUSION: Susceptibility to AE is significantly associated with the HLA-DRB1 *
      040x. HLA-DRB1 * 0701 gene might confer protection against AE in humans.

PMID- 14570624
TI  - Induction of immune responses in mice by vaccination with Liposome-entrapped DNA
      complexes encoding Toxoplasma gondii SAG1 and ROP1 genes.
AB  - OBJECTIVE: To evaluate the immune responses induced by experimental DNA construct
      encoding Toxoplasma gondii (T. gondii) surface antigen1 (SAG1) and rhoptry
      protein 1 (ROP1) in mice as a hybrid gene. METHODS: Truncated SAG1 and ROP1 DNA
      fragments were amplified using polymerase chain reaction (PCR) and inserted into
      pEGFP-N3 vector to construct recombinant plasmid pSAG1-ROP1. NIH3T3 mammalian
      cells were transiently transfected with the DNA construct. Female BALB/c mice
      were given three intramuscular injections of 10 micro g plasmid DNA entrapped in
      liposome. Four weeks after the final booster injection, blood samples were
      collected and subjected to enzyme-linked immuno sorbent assay (ELISA) to
      investigate humoral and cell-mediated immune responses. Reversal transcript
      polymerase chain reaction (RT-PCR) was used to evaluate the transcription of
      inoculated DNA-liposome complex in the injected site. Dot-blot hybridization was
      employed in order to detect whether or not the injected DNA was incorporated into
      the genomic DNA of the immunized mice. RESULTS: Green fluorescence was observed
      in pSAG1-ROP1-transfected cells. Western blot analysis showed antibody
      recognition of the expressed SAG1-ROP1 was between 58 kDa and 75 kDa. No
      expression was observed in blank control plasmid-transfected cells. The sera of
      immunized mice exhibited antibodies to T. gondii tachyzoites and primarily
      interferon-gamma and interlukin-2. RT-PCR showed that the duration of transcribed
      inoculated liposome entrapped DNA in the injected muscular tissue was at least
      ten days post the first injection. Dot-blot hybridization revealed that the
      presence of foreign DNA in the splenocytes and peripheral blood leukocytes was
      transient and that no foreign DNA had inserted into the genomic DNA of mice
      immunized with pSAG1-ROP1. CONCLUSIONS: Immunization with a liposome-encapsulated
      DNA construct encoding the T. gondii SAG1 and ROP1 can induce humoral and cell
      mediated immune responses.

PMID- 14570625
TI  - The site of action of epidural fentanyl: what can be learned by studying the
      difference between infusion and bolus administration? The importance of history,
      one hopes.

PMID- 14570626
TI  - The prevalence of preoperative diastolic filling abnormalities in geriatric
      surgical patients.
AB  - Preoperative assessment of heart function has typically focused on evaluating
      left ventricular ejection fraction (LVEF). Recent evidence suggests that
      diastolic heart failure is common and may cause substantial morbidity and
      mortality. We designed this study to examine the prevalence and potential
      clinical correlates of diastolic filling abnormalities as measured by
      echocardiography in geriatric surgical patients. Patients >=65 yr of age
      undergoing coronary artery surgery without concomitant valvular surgery or those
      with one or more risk factors for cardiovascular disease undergoing noncardiac
      surgery were prospectively studied. Preoperative precordial echocardiography was
      performed for patients undergoing noncardiac surgery, and intraoperative
      transesophageal echocardiography was performed for those undergoing cardiac
      surgery. LVEF and diastolic filling properties including E/A ratio and
      deceleration time were measured. Overall, 251 patients were enrolled. The mean
      age was 72 +/- 7 yr. Multiple linear regression analyses showed that patients
      with a history of myocardial infarction P = 0.021), angina pectoris (beta = 
      6.09, 95% CI: -9.66, -2.52; P = 0.01), and valvular heart disease (beta = -5.05,
      95% CI: -9.56, -0.55; P = 0.028) had lower LVEF than those without such
      conditions. Of the patients with normal LVEF, 61.5% had diastolic filling
      abnormalities. Diastolic filling indices including E/A ratio (beta = -1.11, 95%
      CI -6.02, 3.78; P = 0.65) and deceleration times (beta = -3.42, 95% CI -31.28,
      24.45; P = 0.81) contributed no additional predictive value for LVEF. No clinical
      predictors could be identified to predict diastolic filling abnormalities. For
      patients undergoing noncardiac surgery, analysis of variance demonstrates that
      the clinical assessment of LVEF using history and physical examination data was
      able to grossly discriminate the different levels of LVEF as compared with
      echocardiography (P = 0.0004). However, under-estimation of LVEF occurred more
      frequently than over-estimation. Although physicians' clinical assessment of
      systolic ejection fraction was generally accurate, geriatric patients with normal
      LVEF often had isolated diastolic filling abnormalities that could not be
      predicted by clinical factors. These results suggest that evaluation of LV
      systolic function alone is not discriminatory in comprehensively characterizing
      LV function in geriatric surgical patients. IMPLICATIONS: Although physicians'
      clinical assessment of systolic ejection fraction was generally accurate,
      geriatric patients with normal left ventricular (LV) ejection fraction often had
      isolated diastolic filling abnormalities that could not be predicted by clinical
      factors. These results suggest that evaluation of LV systolic function alone is
      not discriminatory in comprehensively characterizing LV function in geriatric
      surgical patients.

PMID- 14570627
TI  - Mannitol and dopamine in patients undergoing cardiopulmonary bypass: a randomized
      clinical trial.
AB  - In this prospective, randomized, placebo-controlled, double-blinded study, we
      determined the effects of two commonly used adjuncts, mannitol and dopamine, on
      beta(2)-microglobulin (beta(2)M) excretion rates in patients undergoing coronary
      artery bypass graft surgery with cardiopulmonary bypass (CPB). beta(2)M excretion
      rate has been described as a sensitive marker of proximal renal tubular function.
      One-hundred patients with a preoperative serum creatinine level <or=1.5 mg/dL
      were prospectively randomized into 4 groups: 1). placebo, 2). mannitol 1 g/kg
      added to the CPB prime, 3). dopamine 2 microg kg(-1x. min(-1) from the induction
      of anesthesia to 1 h post-CPB, or 4). mannitol plus dopamine. The primary outcome
      measure was beta(2)M excretion rate at 1 h post-CPB. Secondary outcome measures
      included beta(2)M excretion rate at 6 and 24 h post-CPB; urinary flow rate and
      creatinine clearance at 1, 6, and 24 h post-CPB; and the highest postoperative
      serum creatinine level. Length of intensive care stay and hospitalization, as
      well as adverse events, were also considered secondary outcomes. Dopamine
      significantly increased beta(2)M excretion rate at 1 h post-CPB (2.48 +/- 3.61
      microg/min) compared with placebo (0.59 +/- 1.04 microg/min; P = 0.001). This
      effect was not ameliorated by the addition of mannitol (beta(2)M excretion rate,
      2.05 +/- 2.77 microg/min; P = 0.007 compared with placebo). beta(2)M excretion
      rate was similar in patients given placebo or mannitol alone (P = 0.831). Rather
      than being a protective drug in the setting of CPB, dopamine alone or in
      combination with mannitol increases beta(2)M excretion rate, which may be a
      measure of renal tubular dysfunction. The clinical implications of this increase
      and whether it is also seen in patients with established renal dysfunction
      undergoing CPB require additional investigation. IMPLICATIONS: In many clinical
      settings, an increased beta-2-microglobulin (beta(2)M) excretion rate indicates
      renal tubular injury. In this cardiopulmonary bypass (CPB) study, a dopamine
      infusion (alone or with mannitol) resulted in an increased beta(2)M excretion
      rate. It is unclear whether this dopamine-related increase implies renal injury
      after CPB, and further investigations are required to examine the
      mechanism/clinical relevance of this observation.

PMID- 14570628
TI  - Propofol decreases reperfusion-induced arrhythmias in a model of "border zone"
      between normal and ischemic-reperfused guinea pig myocardium.
AB  - We examined the effect of propofol on the main mechanisms involved in
      ischemia/reperfusion-induced arrhythmias (i.e., spontaneous arrhythmias,
      conduction blocks, and dispersion of repolarization) in vitro. In a double
      chamber bath, guinea pig right ventricular muscle strips were subjected to 30 min
      of simulated ischemia followed by 30 min of reperfusion (altered zone; AZ) and to
      standard conditions (normal zone; NZ). Action potential (AP) parameters were
      recorded in the NZ and AZ. We studied the effects of Intralipid(R) and of
      propofol at 10(-6), 10(-5), and 2 x 10(-5) M on the occurrence of spontaneous
      sustained arrhythmias, conduction blocks, and the dispersion of repolarization.
      In NZ, Intralipid and propofol did not significantly modify the AP parameters.
      Propofol, but not Intralipid, lessened the ischemia-induced decrease in AP
      duration (APD) at 90% of repolarization (APD(90)) and attenuated the APD
      dispersion around the "border zone." Propofol did not modify the occurrence of
      ischemia-induced arrhythmias. Propofol 10(-6) M, but not Intralipid or propofol
      at 10(-5) and 2 x 10(-5) M, decreased the occurrence of ischemia-induced
      conduction blocks. Propofol decreased the occurrence of reperfusion-induced
      spontaneous sustained arrhythmias. We conclude that, in vitro, propofol
      attenuated the ischemia-induced APD(90) dispersion around the "border zone" and
      decreased the occurrence of spontaneous arrhythmias related to myocardial
      reperfusion injury. IMPLICATIONS: In isolated guinea pig ventricular myocardium
      propofol, but not Intralipid(R), attenuated the ischemia-induced shortening of
      action potential and, thus, the dispersion of repolarization and decreased the
      occurrence of spontaneous ventricular arrhythmia related to reperfusion injury.
      This result may be important for propofol-based anesthesia in patients at high
      risk for intraoperative ischemia.

PMID- 14570630
TI  - The effects of isoflurane-induced electroencephalographic burst suppression on
      cerebral blood flow velocity and cerebral oxygen extraction during
      cardiopulmonary bypass.
AB  - We investigated the effects of isoflurane-induced burst suppression, monitored
      with electroencephalography (EEG), on cerebral blood flow velocity (CBFV),
      cerebral oxygen extraction (COE), and autoregulation in 16 patients undergoing
      cardiac surgery. The experimental procedure was performed during nonpulsatile
      cardiopulmonary bypass (CPB) with mild hypothermia (32 degrees C) in fentanyl
      anesthestized patients. Middle cerebral artery transcranial Doppler flow
      velocity, right jugular vein bulb oxygen saturation, and jugular venous pressure
      (JVP) were continuously measured. Autoregulation was tested during changes in
      mean arterial blood pressure (MAP) within a range of 40-80 mm Hg, induced by
      sodium nitroprusside and phenylephrine before (control) and during additional
      isoflurane administration to an EEG burst-suppression level of 6-9/min.
      Isoflurane induced a 27% decrease in CBFV (P < 0.05) and a 13% decrease in COE (P
      < 0.05) compared with control. The slope of the positive relationship between
      CBFV and cerebral perfusion pressure (CPP = MAP - JVP) was steeper with
      isoflurane (P < 0.05) compared with control, as was the slope of the negative
      relationship between CPP and COE (P < 0.05). We conclude that burst-suppression
      doses of isoflurane decrease CBFV and impair autoregulation of cerebral blood
      flow during mildly hypothermic CPB. Furthermore, during isoflurane
      administration, blood flow was in excess relative to oxygen demand, indicating a
      loss of metabolic autoregulation of flow. IMPLICATIONS: The effects of isoflurane
      on cerebral blood flow velocity (CBFV) and oxygen extraction (COE) as a function
      of perfusion pressure were studied. When added to fentanyl anesthesia, isoflurane
      induced a 27% and 13% decrease in CBFV and COE, respectively. CBFV became more
      pressure-dependent with isoflurane indicating an impaired autoregulation.

PMID- 14570629
TI  - The sympathomimetic actions of l-ephedrine and d-pseudoephedrine: direct receptor
      activation or norepinephrine release?
AB  - The basic mechanisms by which ephedrine is preferred over other vasopressors in
      obstetric anesthesia have not been clearly defined. We examined the
      sympathomimetic effects of l-ephedrine, currently used as a vasopressor, and d
      pseudoephedrine, currently used as a decongestant. In anesthetized rats, l
      ephedrine and d-pseudoephedrine caused dose-dependent increases in arterial blood
      pressure and heart rate, and these effects disappeared after destruction of the
      sympathetic nerve terminals with 6-hydroxydopamine (6-OHDA) pretreatment. The two
      ephedrine isomers produced concentration-dependent increases in tension of
      anococcygeal muscle and sinus rate of right atrium from rats. However, the
      anococcygeal and atrial responses to d-pseudoephedrine were abolished after 6
      OHDA pretreatment, whereas approximately 50% of the responses to l-ephedrine were
      6-OHDA-resistant. In human umbilical artery and vein, the two isomers failed to
      generate any contraction when given at the concentration that is capable of
      producing significant effects on anococcygeal and atrial tissues. Although direct
      adrenoceptor activation with l-ephedrine was detectable at tissue levels, the
      pressor response in vivo was entirely attributable to norepinephrine release from
      sympathetic nerves. This indirect mechanism could partly explain why l-ephedrine
      is better at increasing maternal arterial blood pressure while preserving the
      uteroplacental blood flow that is devoid of the involvement of the sympathetic
      innervation. IMPLICATIONS: The indirectly sympathomimetic property of l-ephedrine
      may be one of the mechanisms to explain why ephedrine is preferred over alpha
      adrenergic agonists as a vasopressor for treatment of intraspinal anesthesia
      induced hypotension in obstetrics.

PMID- 14570631
TI  - Intrathecal clonidine and severe hypotension after cardiopulmonary bypass.
AB  - The use of intrathecal clonidine as an adjunct for the management of chronic
      pain, intra- and postoperative analgesia is gaining an increase in popularity.
      However, antinociceptive doses of intrathecal clonidine may produce pronounced
      hemodynamic side effects, including hypotension and bradycardia. In this report,
      we present a case of severe hypotension after cardiopulmonary bypass in a patient
      with intrathecal clonidine infusion. We postulate that the intrathecally
      administered alpha 2-agonist clonidine reduced our patient's ability to tolerate
      the hemodynamic lability that is present during the separation from
      cardiopulmonary bypass by potentially inhibiting sympathetic nervous system
      activity, renin-angiotensin system, or vasopressin release. The authors report a
      case of severe hypotension after cardiopulmonary bypass in a patient receiving
      intrathecal clonidine infusion for chronic neuropathic pain.

PMID- 14570632
TI  - Diagnosis of an intraoperative aortic dissection by transesophageal
      echocardiography during routine coronary artery bypass grafting surgery.
AB  - Acute aortic dissection during coronary artery bypass grafting (CABG), though
      rare, causes significant morbidity and mortality. We report a case of
      postcardiopulmonary bypass aortic dissection in a 73-yr-old man who presented for
      CABG. The diagnosis was made by transesophageal echocardiography and allowed
      immediate treatment of the potentially lethal complication. IMPLICATIONS: Acute
      aortic dissection during coronary artery bypass grafting (CABG), though rare
      causes frequent morbidity and mortality. We report a case of postcardiopulmonary
      bypass aortic dissection in a 73-yr-old man who presented for CABG. Diagnosis
      made by transesophageal echocardiography allowed immediate treatment of the
      potentially lethal complication.

PMID- 14570633
TI  - Hemomediastinum resulting from subclavian artery laceration during internal
      jugular catheterization.
AB  - The complications associated with internal jugular vein catheterization are
      inadvertent arterial puncture, pleural and mediastinal injuries, pneumothorax,
      hemothorax, and hemomediastinum. Complications caused by laceration of a
      subclavian artery are rare. We present a case of hemomediastinum resulting from
      laceration of the subclavian artery during central venous catheterization. After
      right internal jugular vein catheterization, the left lateral decubitus position
      was maintained for 6 h during surgery. The severe hypotension was first noted in
      the supine position after transfer to the postanesthesia care unit. Chest
      radiograph showed a bulging of the right upper mediastinum. During the upper half
      sternotomy, a 5-mm long laceration was found at the posteroinferior side of the
      right subclavian artery near its origin from the innominate artery. IMPLICATIONS:
      The authors describe the delayed presentation of hemomediastinum resulting from
      subclavian artery laceration after internal jugular vein catheterization.

PMID- 14570634
TI  - Chemical burn injury secondary to intraoperative transesophageal
      echocardiography.
AB  - We describe a case of a 72-yr-old male who suffered aerodigestive tract chemical
      injury resulting from a probable post-processing residual of the high-level
      disinfectant solution Cidex OPA (ortho-phthalaldehyde) used to disinfect the
      transesophageal echocardiogram probe used for cardiac monitoring during general
      anesthesia. This case highlights the need for strict adherence to manufacturers'
      instructions when using chemical disinfectants for transesophageal echocardiogram
      probe reprocessing. IMPLICATIONS: We describe a case of aerodigestive tract
      chemical injury resulting from a probable post-processing residual of the high
      level disinfectant solution Cidex OPA (ortho-phthalaldehyde) used to disinfect
      the transesophageal echocardiogram probe used during general anesthesia.

PMID- 14570635
TI  - Transcranial Doppler: an early predictor of ischemic stroke after cardiac arrest?
AB  - A 69-yr-old woman was admitted to the intensive care unit after cardiac surgery.
      Immediately after the discontinuation of cardiopulmonary bypass, she had a
      circulatory arrest. A 13-min open-chest cardiac massage was followed by 70 min of
      cardiopulmonary bypass. Right hemiplegia and right extensor plantar reflex were
      noted after the patient awakened. She had been included in a prospective study
      protocol measuring, before and after surgery, cerebral blood flow with
      transcranial Doppler (TCD). The data were retrospectively analyzed, and it was
      established that the TCD had recorded cerebral perfusion defects. This is the
      first case of acute ischemic stroke after cardiac arrest with retrospective
      documentation of asymmetrical cerebral blood flow by a systematic postoperative
      TCD recording. IMPLICATIONS: Clinical neurological examination is often of
      limited value in deeply sedated patients. This case report describes the early
      diagnosis of an ischemic stroke by using transcranial Doppler after cardiac
      surgery. Thus, transcranial Doppler could be used systematically for cerebral
      perfusion monitoring in patients who have undergone major hemodynamic
      instabilities.

PMID- 14570636
TI  - An update on bronchial blockers during lung separation techniques in adults.
AB  - Techniques for one-lung ventilation (OLV) can be accomplished in two ways: The
      first involves the use of a double-lumen endotracheal tube (DLT). The second
      involves blockade of a mainstem bronchus (bronchial blockers). Bronchial blockade
      technology is on the rise, and in some specific clinical situations (e.g.,
      management of the difficult airway during OLV or selective lobar blockade) it can
      offer more as an alternative to achieve OLV in adults. Special emphasis on newer
      information for the use of Fogarty embolectomy catheter as a bronchial blocker,
      the torque control blocker Univent, and the wire-guided endobronchial blocker
      (Arndt blocker) is included. Also this review describes placement, positioning,
      complications, ventilation modalities, and airflow resistances of all three
      bronchial blockers. Finally, the bronchial blockers can be used in many cases
      that require OLV, taking into consideration that bronchial blockers require
      longer time for placement, assisted suction to expedite lung collapse, and the
      use of fiberoptic bronchoscopy. The current use of bronchial blockers, supported
      by scientific evidence, dictates that bronchial blockers should be available in
      any service that performs lung separation techniques.

PMID- 14570637
TI  - Intraoperative transesophageal echocardiography in pediatric congenital cardiac
      surgery: a two-center observational study.
AB  - Transesophageal echocardiography (TEE) is a monitoring and diagnostic tool for
      the care of children undergoing cardiac surgery. We analyzed reports from 865
      routine TEE examinations performed between January 1994 and March 2002 in
      patients younger than 17-yr-old who were undergoing surgery for congenital heart
      disease. Patients' median age was 36 mo (range, 1 day-16 yr). The primary end
      point of the study was the incidence of surgical and medical management decisions
      changed as a result of TEE findings; secondary end-points were diagnostic impact
      (diagnostic exclusions and new diagnoses) and surgical outcome. Fifty percent of
      the examinations were performed by anesthesiologists with an advanced level of
      training in perioperative TEE; all of the examiners had an experience of >or=>500
      TEE examinations. Supervision by an anesthesiologist with an advanced level of
      training was requested in 36.7% of cases; supervision by a cardiologist was
      requested in 3.8%. Surgical alterations of management were reported in 12.7% of
      cases and included the need for a repeat bypass run in 7.3%; medical alterations
      of management were required in 19.4% of cases. We observed a diagnostic impact of
      TEE in 18.5% of cases and a suboptimal but acceptable surgical outcome in 27.6%;
      TEE findings predicted postoperative difficulties in 4.0%. Our results confirm
      the utility of routine TEE to assess repair of congenital heart defects.
      Furthermore, this service was competently performed by a regular team of cardiac
      anesthesiologists appropriately trained in TEE. IMPLICATIONS: Transesophageal
      echocardiography (TEE) is an essential monitoring and diagnostic device for the
      care of children undergoing cardiac surgery. The surgical and medical impact of
      TEE is demonstrated in a large series of patients. This service can be performed
      by appropriately trained cardiac anesthesiologists.

PMID- 14570638
TI  - Pulse contour analysis for cardiac output monitoring in cardiac surgery for
      congenital heart disease.
AB  - Conventional methods of cardiac output monitoring using pulmonary artery
      catheters may not be feasible in patients with congenital heart disease because
      of patients' small size or aberrant anatomy. We studied the accuracy of a new
      device, which uses pulse contour analysis to measure continuous cardiac output,
      in children and adults undergoing congenital heart surgery. Sixteen patients,
      median ages 7 yr old, were included in this prospective study. One-hundred-ninety
      one data points were obtained in the pre- and postcardiopulmonary bypass periods
      and in the first 12 h after intensive care unit admission. We evaluated the
      relationship between cardiac index (CI) derived from transpulmonary
      thermodilution (TDCI) and CI derived from pulse contour analysis (PCCI). Bias and
      limits of agreement between TDCI and PCCI over all time periods were 0.1 +/-
      1.94, indicating a wide dispersion of the data. Coefficient of correlation (r)
      between the TDCI and PCCI was 0.7. Although in previous studies, PCCI has been
      suggested to be accurate in adult cardiac surgery, we found it to be less
      reliable in our study patients, even after shunt correction. The relationships of
      the volume and pressure based measures of preload, intrathoracic blood volume
      index (ITBI), and central venous pressure with CI were also investigated. After
      repair, correlation (r) between PCCI or TDCI and ITBI (0.56 and 0.71,
      respectively) was better than that between PCCI or TDCI and CVP (0.16 and 0.11,
      respectively), indicating greater validity of ITBI as a measure of preload.
      IMPLICATIONS: Our results suggest that the pulse contour analysis cardiac output
      (CO) monitoring in patients undergoing congenital heart surgery may not provide
      as accurate or reliable measures of CO as previously suggested. The volume-based
      variable of preload intrathoracic blood volume index (ITBI) has better
      correlation with cardiac index (CI) than the central venous pressure, suggesting
      that ITBI may be a better indicator of preload.

PMID- 14570639
TI  - Tissue factor-activated thromboelastograms in children undergoing cardiac
      surgery: baseline values and comparisons.
AB  - Activation of clotting with tissue factor (TF) allows rapid evaluation of
      thromboelastograms but alters the values of thromboelastogram variables. We have
      performed TF-activated thromboelastograms in 250 children <2 yr old undergoing
      cardiac surgery to establish baseline values. Five groups were distinguished to
      evaluate the effects of quantitative deficiencies in coagulation factor levels
      during infancy: <30 days, 1-3 mo, 3-6 mo, 6-12 mo, and 12-24 mo. Activation of
      clotting (R and K values) was similar among groups. Infants 1-3 mo of age
      demonstrated increased clot strength compared with the other groups, a finding
      similar to previous evaluation of native thromboelastograms. The alpha and
      maximum amplitude values were numerically almost identical in each age group, a
      unique finding in activated thromboelastograms. Fibrinolysis was similar among
      groups. We believe that knowledge of baseline TF-activated thromboelastogram
      variables in young children will be useful in interpreting these
      thromboelastograms in clinical scenarios, in using these thromboelastograms as
      part of coagulopathy treatment algorithms, and during the application of more
      specific thromboelastogram modifiers. Additionally, the similarity of alpha and
      maximum amplitude values in each age group will allow even faster interpretation
      of thromboelastogram data. IMPLICATIONS: Baseline values for tissue factor
      activated thromboelastograms in young children undergoing cardiac surgery have
      been established and will permit accurate use and interpretation of this
      thromboelastogram modification in evaluating and managing coagulopathies.

PMID- 14570641
TI  - Fiberoptic tracheal intubation through a laryngeal mask airway in a child with
      Treacher Collins syndrome.
AB  - Treacher Collins syndrome (TCS) is a rare inherited condition characterized by
      bilateral and symmetric abnormalities of structures within the first and second
      bronchial arches. The mechanism of inheritance is autosomal dominant with
      variable expressivity. Because of this variability in expression, some affected
      individuals exhibit virtually no overt clinical manifestations. However, most
      children with TCS present with the following classic facial features: down
      sloping palpebral fissures, colobomata of the lower eyelid, scanty lower
      eyelashes, malar hypoplasia, and micro- or retrognathia. Cleft palate is present
      in up to 35% of patients and an additional 30-40% have congenital
      palatopharyngeal incompetence. Abnormalities of the ear are very common and vary
      from minor malformations to severe microtia and hearing loss. Hearing loss may be
      due to atresia of the auditory canals or ossicular malformation of the middle
      ear. Despite these many development abnormalities, TCS patients are usually of
      normal intelligence. We report the case of a 3 1/2-yr-old patient with TCS
      undergoing cleft palate repair and discuss fiberoptic intubation through a
      laryngeal mask airway using two endotracheal (ETT) tubes secured via an ETT
      connector.

PMID- 14570640
TI  - Pretreatment with small-dose ketamine reduces withdrawal movements associated
      with injection of rocuronium in pediatric patients.
AB  - We evaluated the pretreatment of small-dose of ketamine or normal saline in the
      reduction of withdrawal movements induced by rocuronium injection. One-hundred
      pediatric patients (aged 1-6 yr) were randomly assigned into 2 groups. A 22-gauge
      IV cannula was inserted into the dorsum of the hand, and ketamine 0.2 mg/kg or
      normal saline was given, followed by a 5 mg/kg thiopental injection 10 s later.
      IV rocuronium (0.8 mg/kg) was injected over 5 s. The patient's response to
      rocuronium injection was graded by using a four-point scale in a double-blinded
      manner. We observed that the incidence of withdrawal movements was 83% in the
      saline group and 27% in patients pretreated with ketamine (P < 0.05). Some
      patients in both groups developed skin erythema at the site of injection. We
      conclude that pretreatment with small-dose ketamine significantly attenuates
      withdrawal movements associated with IV injection of rocuronium in pediatric
      patients anesthetized with thiopental. IMPLICATIONS: Pretreatment with small-dose
      ketamine 0.2 mg/kg provides a simple and safe means of reducing the incidence of
      withdrawal movements induced by the injection of rocuronium, a short-acting
      nondepolarizing muscle relaxant.

PMID- 14570642
TI  - Sciatic nerve block in a child: a sonographic approach.
AB  - Ultrasound technology can facilitate peripheral nerve blocks in clinical
      practice. In this case report, ultrasound imaging was used to identify the
      sciatic nerve and guide local anesthetic injection in the subgluteal region of a
      child undergoing Achilles tendon lengthening. Sonographic guidance may be
      especially useful for peripheral nerve blocks in children because the neural
      imaging is often excellent and reference landmarks are variable. IMPLICATIONS: In
      this case report, ultrasound was used to identify the sciatic nerve and guide
      local anesthetic injection in the subgluteal region of a child. Sonographic
      guidance may be especially useful for peripheral nerve blocks in children because
      the neural imaging is often excellent and reference landmarks are variable.

PMID- 14570643
TI  - The use of a continuous popliteal sciatic nerve block after surgery involving the
      foot and ankle: does it improve the quality of recovery?
AB  - Popliteal sciatic nerve block is a commonly used technique for surgery involving
      the foot and ankle. However, pain can be difficult to control as the local
      anesthetic block wears off. Therefore, we hypothesized that extending the block
      by using a continuous infusion of bupivacaine (0.25%) would provide improved pain
      management and might facilitate the recovery process after foot or ankle surgery.
      In this randomized, double-blinded, placebo-controlled study, 24 consenting
      patients undergoing foot or ankle surgery with a standardized general anesthetic
      technique were studied. Before surgery, a popliteal sciatic nerve block was
      performed in all patients with an 18-gauge Tuohy epidural needle and a peripheral
      nerve stimulator. After injection of bupivacaine 0.25% 30 mL and placement of a
      20-gauge catheter, patients were randomly assigned to receive either 0.9% saline
      (control) or bupivacaine 0.25% at a constant rate of 5 mL/h for up to 48 h after
      surgery. An 11-point verbal rating scale (0 = no pain to 10 = worst pain
      imaginable) was used to assess the severity of pain. Opioid analgesic use was
      recorded at specific time intervals after surgery. Follow-up evaluations were
      performed at 24 h, 48 h, 72 h, and 1 week after surgery to assess pain scores, as
      well as patient satisfaction with their pain management and quality of recovery,
      by using a 100-point verbal rating scale (1 = highly dissatisfied to 100 = highly
      satisfied). In the bupivacaine group, there was a statistically significant
      reduction in the maximal pain scores (>50%) and in opioid use (>60%) during the
      postoperative period compared with the control group. Patient satisfaction with
      postoperative pain management (95 +/- 3 versus 77 +/- 13) and quality of recovery
      (96 +/- 7 versus 83 +/- 14) was significantly improved in the bupivacaine group
      (versus control). In addition, 40% of the patients in the bupivacaine group
      (versus none in the control group) were able to be discharged home on the day of
      surgery (P = 0.087). In conclusion, a continuous infusion of bupivacaine 0.25%
      decreased postoperative pain and the need for opioid analgesic rescue medication
      after orthopedic surgery involving the foot and ankle, leading to improved
      patient satisfaction and quality of recovery. IMPLICATIONS: A continuous infusion
      of bupivacaine 0.25% (versus saline) at the popliteal fossa by using a simple
      elastomeric pump is an effective method of decreasing postoperative pain,
      reducing the opioid analgesic requirement, and increasing patient satisfaction
      with pain management after orthopedic surgery involving the foot and ankle. More
      importantly, the use of the continuous sciatic nerve block in the popliteal fossa
      facilitated an earlier discharge after lower extremity surgery.

PMID- 14570644
TI  - Facial skin injuries caused by adhesive tapes in a patient receiving cosmetic
      skin exfoliants.
AB  - A 39-yr-old woman underwent general anesthesia for laparoscopic sterilization. We
      used adhesive tapes to close her eyelids and to secure the tracheal tube. Removal
      of the tapes caused patchy areas of skin loss. We later discovered that the
      patient had fragile facial skin from cosmetics containing skin exfoliants. We
      recommend taking a detailed drug history before anesthesia and avoiding adhesive
      tapes to the patient's face under general anesthesia.

PMID- 14570646
TI  - Lidocaine and octanol have different modes of action at tetrodotoxin-resistant
      Na(+) channels of peripheral nerves.
AB  - Local anesthetics and alcohols block impulse conduction in peripheral nerves by
      inhibiting Na(+) currents. In small peripheral nerve fibers, tetrodotoxin
      resistant (TTX-r) Na(+) channels play an important role in impulse generation. We
      investigated the effects of lidocaine and the alcohol octanol on TTX-r Na(+)
      channels. Currents were recorded with the whole-cell patch-clamp method from
      enzymatically isolated rat dorsal root ganglion cells (data evaluation: nonlinear
      least-squares fitting). Lidocaine and octanol blocked the TTX-r Na(+) current in
      a reversible and concentration-dependent manner (50% inhibitory concentration
      values: 177 +/- 25 and 455 +/- 25 microM, respectively). Lidocaine additionally
      produced a strong use-dependent block. Both drugs showed a strong dynamic block
      (i.e., block developed during the time course of current activation and
      inactivation). Double-pulse protocols showed a slow dissociation of lidocaine
      from the channel during repolarization (time constant: 1763 +/- 63 ms; 300
      microM). The dissociation of octanol was too quick to be distinguished from
      normal current repriming kinetics of 2.2 ms. Lidocaine and octanol acted
      noncompetitively in the Na(+) channel. Lidocaine and octanol have different
      blocking properties on the TTX-r Na(+) current and bind to different channel
      sites. IMPLICATIONS: Lidocaine and octanol have different inhibitory effects on
      the function of tetrodotoxin-resistant Na(+) channels in rat dorsal root ganglion
      cells, as well as noncompetitive modes of action, as investigated by the whole
      cell patch-clamp method, and therefore are likely to have different binding sites
      on the channel.

PMID- 14570645
TI  - Lidocaine attenuates monocyte chemoattractant protein-1 production and chemotaxis
      in human monocytes: possible mechanisms for its effect on inflammation.
AB  - The recruitment and activation of peripheral blood monocytes are potentially
      critical regulatory events for the control of inflammation. Increased levels of
      monocyte chemoattractant protein (MCP)-1 have been reported in several
      inflammatory disorders. In this study, we examined the effect of lidocaine on
      lipopolysaccharide-stimulated MCP-1 secretion and MCP-1 induced chemotaxis in a
      human monocytic cell line, THP-1. Lidocaine inhibited lipopolysaccharide-induced
      MCP-1 production as well as messenger RNA expression in a dose-dependent manner.
      Furthermore, we demonstrated that lidocaine suppressed MCP-1-induced chemotaxis
      and peak cytosolic-free calcium in THP-1 cells. These results suggest that
      lidocaine may modulate MCP-1 production and MCP-1-induced activation in
      inflammatory cells. IMPLICATIONS: Monocyte chemoattractant protein-1 (MCP-1)
      plays important roles in the inflammatory processes. Lidocaine may modulate MCP-1
      induced monocyte response, as reflected by chemotaxis, cytosolic-free calcium,
      and lipopolysaccharide-induced MCP-1 production by human monocytic THP-1 cells.

PMID- 14570647
TI  - Inhibition by propofol of intracellular calcium mobilization in cultured mouse
      pituitary cells.
AB  - Propofol inhibited regulated secretion of the neuropeptide beta-endorphin from
      AtT-20 cells, a pituitary tumor cell line. Neuropeptide secretion depends on an
      increase of intracellular calcium (Ca(2+)) levels. We investigated the hypothesis
      that propofol altered intracellular Ca(2+) levels in AtT-20 cells. Propofol (100
      microM) did not inhibit Ca(2+)-induced secretion of beta-endorphin from digitonin
      permeabilized cells. Thus, propofol did not inhibit neuropeptide secretion by
      blocking the effects of increased intracellular Ca(2+). Intracellular Ca(2+) was
      measured in intact cells using a Ca(2+)-sensitive dye. Ca(2+) transients were
      generated by depolarization with KCl or by incubation with thapsigargin (an
      inhibitor of Ca(2+) uptake into the endoplasmic reticulum). Propofol inhibited
      generation of Ca(2+) transients in intact cells by KCl (half-maximal inhibitory
      concentration of 14.9 microM; P < 0.05). Nitrendipine also inhibited potassium
      induced Ca(2+) peaks. Propofol 50 microM reduced the thapsigargin-induced Ca(2+)
      peak to 47% of control (P < 0.05). Thapsigargin-induced Ca(2+) peaks were not
      affected by calcium channel blockade by nitrendipine. Propofol inhibited the
      stimulus-induced increase in intracellular Ca(2+). Propofol inhibited
      thapsigargin-induced Ca(2+) transients, but nitrendipine did not, indicating that
      propofol had effects on intracellular Ca(2+) independent of blockade of L-type
      Ca(2+) channels. Propofol may inhibit release of Ca(2+) from intracellular
      stores. These results are consistent with the hypothesis that propofol inhibits
      neuropeptide secretion by inhibiting the stimulus-induced increase in
      intracellular Ca(2+). IMPLICATIONS: Propofol may block both entry of calcium into
      cells and release of calcium from intracellular stores, thereby inhibiting
      regulated secretion of neuropeptides. Study of the effects of propofol on
      intracellular calcium metabolism may increase understanding of how propofol
      alters brain function and may aid development of better IV anesthetics.

PMID- 14570648
TI  - Suppression of natural killer cell activity and promotion of tumor metastasis by
      ketamine, thiopental, and halothane, but not by propofol: mediating mechanisms
      and prophylactic measures.
AB  - Postoperative immunosuppression is partly ascribed to anesthesia and has been
      suggested to compromise patients' resistance to infection and tumor metastasis.
      We compared the effects of various anesthetics on natural killer (NK) cell
      activity and on resistance to experimental metastasis, and studied mediating
      mechanisms and prophylactic measures. Fischer 344 rats served as controls or were
      anesthetized for 1 h with ketamine, thiopental, halothane, or propofol.
      Anesthetized rats were either maintained in normothermia or left to spontaneously
      reach 33 degrees C-35 degrees C. Rats were then injected IV with MADB106 tumor
      cells, and 24 h later lung tumor retention was assessed, or 3 wk later, lung
      metastases were counted. Additionally, the number and activity of circulating NK
      cells were assessed after anesthesia. All anesthetics, except propofol,
      significantly reduced NK activity and increased MADB106 lung tumor retention or
      lung metastases. Hypothermia had no significant effects. Ketamine increased
      metastasis most potently, and this effect was markedly reduced in rats pretreated
      with a beta-adrenergic antagonist (nadolol) or with chronic small doses of an
      immunostimulator (polyriboinosinic:polyribocytidylic acid). Overall, the marked
      variation in the NK-suppressive effects of anesthetics seems to underlie their
      differential promotion of MADB106 metastasis. Prophylactic measures may include
      perioperative immunostimulation and the use of beta-blockers. IMPLICATIONS: This
      study in a rat model of pulmonary metastasis demonstrates that some anesthetics,
      but not others, increase susceptibility to tumor metastasis, apparently by
      suppressing natural killer cell activity. Ketamine was most deleterious, and its
      effects were prevented by peripheral blockade of beta-adrenoceptors combined with
      low levels of immunostimulation.

PMID- 14570649
TI  - An animal model for surgical anesthesia and analgesia: characterization with
      isoflurane anesthesia and remifentanil analgesia.
AB  - With a traditional clamp test alone, quantitative evaluation of the level of
      surgical anesthesia/analgesia is not easy. We have developed a rabbit model that
      allows for repeated quantification of the varying level of surgical
      anesthesia/analgesia using both mechanical and electrical stimulation as
      simulated surgical stimuli. After tracheostomy and intravascular cannulations
      under isoflurane anesthesia, eight rabbits were placed on a sling that allowed
      for free movement of the head and extremities. The inspired isoflurane
      concentration was reduced from 3% to 1.5% and then to 0%. Remifentanil was then
      infused at 4 graded infusion rates (0.1-0.8 microg. kg(-1) x min(-1)). At each
      drug dose, analgesic variables were determined including the number of animals
      behaviorally unresponsive to clamping the forepaw (nonresponders) and threshold
      voltage of subcutaneous electrical stimulation (2 Hz, 5 Hz, and 50 Hz) required
      to evoke the head lift (HLT, pain detection/arousal threshold) and escape
      movement responses (EMT, pain tolerance threshold). With increasing drug doses,
      HLTs and EMTs at 5 Hz increased dose-dependently and most proportionately to
      increases in the number of nonresponders, a standard indicator of the
      anesthetic/analgesic level. Therefore, using the HLT and EMT at 5 Hz combined
      with a clamp test, this rabbit model allows for quantitative evaluation of the
      varying level of surgical anesthesia/analgesia. IMPLICATIONS: We have developed a
      rabbit model of surgical anesthesia and analgesia using both mechanical and
      electrical stimulation as simulated surgical stimuli, which allows for repeated,
      quantitative, and qualitative evaluation of the varying level of surgical
      anesthesia and analgesia, differentiation between sedative/hypnotic and analgesic
      components of drug actions, and simultaneous monitoring of all the clinically
      relevant physiological variables including cardiovascular and respiratory
      variables.

PMID- 14570650
TI  - Detection of acute tolerance to the analgesic and nonanalgesic effects of
      remifentanil infusion in a rabbit model.
AB  - Although acute tolerance to analgesia develops rapidly with remifentanil, it is
      unknown whether acute tolerance also develops to its nonanalgesic effects. We
      investigated the analgesic and cardiorespiratory effects of remifentanil during a
      continuous infusion in a rabbit model. Ten tracheotomized New Zealand White
      rabbits with arterial and venous accesses were placed on a sling that allowed for
      reasonably free movement. In spontaneously breathing conscious animals,
      remifentanil was infused IV at a constant-rate of 0.3 microg kg(-1)x min(-1) for
      360 min. Sedative/analgesic and cardiorespiratory variables were assessed
      repeatedly during remifentanil infusion, including the number of animals
      behaviorally unresponsive to clamping the forepaw (nonresponders) and
      subcutaneous electrical stimulation thresholds required to elicit head lift (HLT:
      pain detection/arousal threshold) and escape movement responses (EMT: pain
      tolerance threshold). Within 60-120 min of starting the infusion, the number of
      nonresponders, HLT, EMT, and PaCO(2) increased significantly, whereas blood
      pressure, heart rate, and respiratory rate decreased. Thereafter, all variables
      returned towards preinfusion levels despite continuing infusion. These results
      indicate that during a remifentanil infusion acute tolerance develops for both
      its analgesic and cardiorespiratory effects. IMPLICATIONS: Using a new rabbit
      model, we found that during continuous, constant-rate remifentanil infusion acute
      tolerance developed within the first few hours, not only to its analgesic but
      also to its cardiovascular and respiratory effects, albeit in slightly different
      time courses.

PMID- 14570651
TI  - Thiamylal and pentobarbital have opposite effects on human platelet aggregation
      in vitro.
AB  - The effects of barbiturates on human platelet function are not fully understood.
      We designed the present study to clarify the effects of thiamylal and
      pentobarbital on human platelet aggregation and to elucidate the underlying
      mechanisms in vitro. Human platelet aggregation induced by adenosine diphosphate
      (ADP), epinephrine, arachidonic acid (AA), and (+)-9,11-epithia-11,12-methano
      thromboxane A(2) (STA(2)), measured with an 8-channel light transmission
      aggregometer, was compared in the absence and presence of thiamylal or
      pentobarbital. To estimate thromboxane A(2) (TXA(2)) receptor binding affinity,
      Scatchard analysis was done using [(3)H]-S145, a specific TXA(2) receptor
      antagonist. STA(2)-TXA(2) receptor binding assay was also examined. The release
      of AA was determined in platelets preincubated with [(3)H]-AA and stimulated by
      ADP, using a liquid scintillation analyzer. Cytosolic free calcium concentration
      ([Ca(2+)](i)) was measured in fluo-3/AM-loaded platelets using a fluorometer.
      Thiamylal enhanced, but pentobarbital suppressed, ADP- and epinephrine-induced
      platelet aggregation, but they did not affect AA- or STA(2)-induced platelet
      aggregation. They had no effect on TXA(2) receptor binding affinity. Although
      thiamylal increased and pentobarbital decreased release of [(3)H]-AA from ADP
      stimulated platelets, both barbiturates had no effect on ADP-induced [Ca(2+)](i)
      increase. We conclude that thiamylal enhances but pentobarbital suppresses human
      platelet aggregation in vitro. These effects of barbiturates are mediated by
      altered AA release without affecting [Ca(2+)](i) increase. IMPLICATIONS:
      Thiamylal enhances but pentobarbital suppresses human platelet aggregation in
      vitro. These effects are attributed to altered arachidonic acid release from
      platelets, possibly by the effects of phospholipase A(2), but not secondary to
      altered cytosolic free calcium concentration.

PMID- 14570652
TI  - The effect of intravenous pantoprazole and ranitidine for improving preoperative
      gastric fluid properties in adults undergoing elective surgery.
AB  - We studied pantoprazole, a new potent and fast-acting proton pump inhibitor. Its
      effects on preoperative gastric fluid volume and pH have not yet been determined.
      In this randomized, controlled trial, we examined the effects of preoperative IV
      pantoprazole or ranitidine on gastric pH and volume. Ninety patients (ASA status
      I and II, scheduled for elective surgery) were studied. One hour before surgery,
      patients in Group I (n = 30) were given IV saline 5 mL, those in Group II (n =
      30) were given 40 mg of pantoprazole IV, and those in Group III (n = 30) were
      given 50 mg of ranitidine IV. A nasogastric tube was inserted immediately after
      anesthesia induction. Gastric contents were aspirated, and volume and pH were
      recorded. The pH values determined in Group I were 3.73 +/- 0.82; in Group II,
      they were 5.30 +/- 1.84; and in Group III, they were 4.80 +/- 1.40. There was no
      statistical difference between Groups 2 and 3, but there was a significant
      difference between Group I and Groups 2 and 3 (P < 0.0005). The volume of the
      gastric contents was 28.67 +/- 10.98 mL in Group I, 15.20 +/- 15.52 mL in Group
      II, and 7.77 +/- 11.17 mL in Group III. There was no statistical difference
      between Groups 2 and 3, but there was a statistically significant difference
      between Group I and Groups 2 and 3 (P < 0.0005). The proportion of patients
      considered "at risk" of significant lung injury should aspiration occur was 20%
      of Group I, 10% of Group II, and 3.3% of Group III. When statistically evaluated,
      there was no difference among groups. We concluded that the administration of IV
      pantoprazole and ranitidine 1 h before surgery is effective in reducing gastric
      pH and volume. IMPLICATIONS: This randomized, controlled trial examined the
      effects of preoperative IV pantoprazole or ranitidine on gastric pH and volume.
      We concluded that IV pantoprazole and ranitidine, given 1 h before surgery, are
      effective in reducing gastric pH and volume.

PMID- 14570653
TI  - Minimum anesthetic concentration of sevoflurane with different xenon
      concentrations in swine.
AB  - In a previous study, we described a partial antagonism of xenon (Xe) in
      combination with isoflurane. One hypothetical explanation suggested that Xe and
      isoflurane probably induced anesthesia via different pathways at the neuronal
      level. This warranted investigating the combination of Xe with other inhaled
      anesthetics to examine the relationship between Xe and volatile anesthetics in
      general. We therefore investigated the influence of Xe on the minimum alveolar
      concentration (MAC) of sevoflurane. The study was performed in 10 swine (weight
      30.8 kg +/- 2.6, mean +/- SD) ventilated with xenon 0%, 15%, 30%, 40%, 50%, and
      65% in oxygen. At each Xe concentration, various concentrations of sevoflurane
      were administered in a stepwise design. For each a supramaximal pain stimulus
      (claw clamp) was applied. The appearance of a withdrawal reaction was recorded.
      The sevoflurane MAC was defined as the end-tidal concentration required to
      produce a 50% response rate. At each Xe concentration, the animals' responses to
      the pain stimulus were categorized and a logistic regression model was fitted to
      the results to determine sevoflurane MAC. Sevoflurane MAC was decreased by
      inhalation of Xe in a linear manner from 2.53 with 0% Xe to 1.54 with 65% Xe. In
      contrast to Xe and isoflurane, the anesthetic effects of Xe and sevoflurane
      appear to be simply linear. IMPLICATIONS: We investigated the influence of the
      anesthetic gas, xenon, on the minimum alveolar concentration (MAC) for the
      volatile anesthetic sevoflurane. The study was performed in 10 swine ventilated
      with fixed xenon and various concentrations of isoflurane. The sevoflurane MAC is
      decreased by inhalation of xenon in a linear relationship.

PMID- 14570654
TI  - The cardioprotective effect of sevoflurane depends on protein kinase C
      activation, opening of mitochondrial K(+)(ATP) channels, and the production of
      reactive oxygen species.
AB  - Several studies suggest that the cardioprotective effect of sevoflurane depends
      on protein kinase C (PKC) activation, mitochondrial K(+)(ATP) channel
      (mitoK(+)(ATP)) opening, and reactive oxygen species (ROS). However, evidence for
      their involvement was obtained in separate experimental models. Here, we studied
      the relative roles of PKC, mitoK(+)(ATP), and ROS in sevoflurane-induced
      cardioprotection in one model. Rat trabeculae were subjected to simulated
      ischemia by applying metabolic inhibition (MI) through buffer containing NaCN,
      followed by 60-min reperfusion. Recovery of active force (F(a)) was assessed as
      percentage of pre-MI force. In time controls, F(a) amounted 60% +/- 5% at the end
      of the experiment. The recovery of F(a) after MI was reduced to 28% +/- 5% (P =
      0.045 versus time control), whereas sevoflurane reversed the detrimental effect
      of MI (F(a) recovery, 67% +/- 8%; P = 0.01 versus MI). The PKC inhibitor
      chelerythrine, the mitoK(+)(ATP) inhibitor 5-hydroxy decanoic, and the ROS
      scavenger N-(2-mercaptopropionyl)-glycine all completely abolished the protective
      effect of sevoflurane (recovery of F(a), 31% +/- 8%, 33% +/- 8%, and 24% +/- 9%
      for chelerythrine, 5-hydroxy decanoic, and N-(2-mercaptopropionyl)-glycine,
      respectively). In conclusion, PKC activation, mitoK(+)(ATP) channel opening, and
      ROS production are all essential for sevoflurane-induced cardioprotection. These
      signaling events are arranged in series within a common signaling pathway, rather
      than in parallel cascades. Our findings implicate that the perioperative use of
      sevoflurane preserves cardiac function by preventing ischemia-reperfusion injury.
      IMPLICATIONS: Protein kinase C, mitochondrial K(+)(ATP) channels and reactive
      oxygen species act within one downstream signaling pathway in mediating the
      cardioprotective effect of sevoflurane.

PMID- 14570655
TI  - The effects of single-dose dexamethasone on wound healing in rats.
AB  - Dexamethasone effectively decreases the incidence of nausea and vomiting among
      pediatric and adult patients. In this study, we evaluated the effects of single
      dose dexamethasone on wound healing in a prospective, randomized, experimental
      animal model. Anesthesia was induced with thiopental 100 mg/kg intraperitoneally.
      Dexamethasone 1 mg/kg was administered intraperitoneally in a dexamethasone
      group, and physiological saline was administered in a control group.
      Collagenization, epithelization, and fibroblast content were significantly less
      in the dexamethasone group compared with the control group (P values of 0.002,
      0.041, and 0.023, respectively). The vascularity and the degree of inflammatory
      cells were more intense in the dexamethasone group compared with the control
      group (P values of 0.023 and 0.002, respectively). The white blood cell count was
      similar in the control (7.84 +/- 2.09) and dexamethasone (6.98 +/- 2.12) groups.
      The mean hydroxyproline level was 0.72 +/- 0.13 mg/g in the dexamethasone and
      1.03 +/- 0.19 mg/g in the control group. Hydroxyproline levels were significantly
      less in the dexamethasone group (P = 0.001). We conclude that dexamethasone at 1
      mg/kg may have negative effects on wound healing. IMPLICATIONS: We evaluated the
      effects of dexamethasone on wound healing in a prospective, randomized,
      experimental animal model. Our results show that dexamethasone at 1 mg/kg may
      have negative effects on wound healing.

PMID- 14570656
TI  - Anaphylaxis during the perioperative period.
AB  - Anesthesiologists use a myriad of drugs during the provision of an anesthetic.
      Many of these drugs have side effects that are dose related, and some lead to
      severe immune-mediated adverse reactions. Anaphylaxis is the most severe immune
      mediated reaction; it generally occurs on reexposure to a specific antigen and
      requires the release of proinflammatory mediators. Anaphylactoid reactions occur
      through a direct non-immunoglobulin E-mediated release of mediators from mast
      cells or from complement activation. Muscle relaxants and latex account for most
      cases of anaphylaxis during the perioperative period. Symptoms may include all
      organ systems and present with bronchospasm and cardiovascular collapse in the
      most severe cases. Management of anaphylaxis includes discontinuation of the
      presumptive drug (or latex) and anesthetic, aggressive pulmonary and
      cardiovascular support, and epinephrine. Although a serum tryptase confirms the
      diagnosis of an anaphylactic reaction, the offending drug can be identified by
      skin-prick, intradermal testing, or serologic testing. Prevention of recurrences
      is critical to avoid mortality and morbidity.

PMID- 14570657
TI  - Human auditory steady-state responses: the effects of recording technique and
      state of arousal.
AB  - There is some controversy in the literature about whether auditory steady-state
      responses (ASSRs) can be reliably recorded in all subjects and whether these
      responses consistently decrease in amplitude during drowsiness. In 10 subjects,
      40-Hz ASSRs became significantly different from background electroencephalogram
      activity with a probability of P < 0.01 and an average time of 22 s (range, 2-92
      s), provided that the responses were analyzed with time-domain averaging rather
      than spectral averaging. In a second experiment with 10 subjects, 40-Hz ASSRs
      recorded between the vertex and posterior neck consistently decreased in
      amplitude during drowsiness and sleep. Findings that the ASSR may occasionally
      increase during drowsiness may be explained by postauricular muscle responses
      recorded from a mastoid reference. These may occur during drowsiness in
      association with rolling-eye movements. ASSRs recorded between the vertex and
      posterior neck are not distorted by these reflexes. These findings combine with
      previous literature on the effects of general anesthetics on the ASSR to confirm
      that the ASSR is a valid option for monitoring the hypnotic effects of general
      anesthetics. IMPLICATIONS: Auditory steady-state responses to stimuli presented
      at rates near 40 Hz can be used to monitor anesthesia. These responses can be
      quickly and reliably recorded during both sleep and wakefulness, provided that
      appropriate averaging techniques are used.

PMID- 14570658
TI  - Evaluation of graphic cardiovascular display in a high-fidelity simulator.
AB  - "Human error" in anesthesia can be attributed to misleading information from
      patient monitors or to the physician's failure to recognize a pattern. A graphic
      representation of monitored data may provide better support for detection,
      diagnosis, and treatment. We designed a graphic display to show hemodynamic
      variables. Twenty anesthesiologists were asked to assume care of a simulated
      patient. Half the participants used the graphic cardiovascular display; the other
      half used a Datex As/3 monitor. One scenario was a total hip replacement with a
      transfusion reaction to mismatched blood. The second scenario was a radical
      prostatectomy with 1.5 L of blood loss and myocardial ischemia. Subjects who used
      the graphic display detected myocardial ischemia 2 min sooner than those who did
      not use the display. Treatment was initiated sooner (2.5 versus 4.9 min). There
      were no significant differences between groups in the hip replacement scenario.
      Systolic blood pressure deviated less from baseline, central venous pressure was
      closer to its baseline, and arterial oxygen saturation was higher at the end of
      the case when the graphic display was used. The study lends some support for the
      hypothesis that providing clinical information graphically in a display designed
      with emergent features and functional relationships can improve clinicians'
      ability to detect, diagnose, manage, and treat critical cardiovascular events in
      a simulated environment. IMPLICATIONS: A graphic representation of monitored data
      may provide better support for detection, diagnosis, and treatment. A user
      centered design process led to a novel object-oriented graphic display of
      hemodynamic variables containing emergent features and functional relationships.
      In a simulated environment, this display appeared to support clinicians' ability
      to diagnose, manage, and treat a critical cardiovascular event in a simulated
      environment. We designed a graphic display to show hemodynamic variables. The
      study provides some support for the hypothesis that providing clinical
      information graphically in a display designed with emergent features and
      functional relationships can improve clinicians' ability to detect, diagnosis,
      mange, and treat critical cardiovascular events in a simulated environment.

PMID- 14570659
TI  - Novel, adjustable, clinical bymixer measures mixed expired gas concentrations in
      anesthesia circle circuit.
AB  - We have introduced a novel, parallel design into a new clinical bymixer (patent
      pending), named for the bypass of a constant fraction of total flow through a
      mixing chamber. Over a wide range of tidal volumes (300-1200 mL), frequency (6-20
      breaths/min), and PCO(2) (6-50 mm Hg), the bymixer provided accurate measurement
      of mixed expired gas fractions in the ventilation circuit compared with an
      expired gas collection in a metabolic lung bench setup (average slope, 1.00;
      average y intercept, -0.01; average coefficient of determination, R(2) = 0.9988).
      Simple changes in mixing chamber volume provided adjustable bymixer response
      times. The fast bymixer response (time constant, 6.4 s) should allow measurements
      to be updated every 20 s (where 95% response occurs by three time constants). The
      new clinical bymixer is constructed from standard anesthesia circuit components,
      attaches easily to the anesthesia machine inspired outlet and expired inlet
      ports, is simple to clean and sterilize, and has no reservoir to trap condensed
      water vapor from expired gas. The new clinical bymixer may facilitate indirect
      calorimetry (CO(2) elimination, VCO(2), and oxygen uptake, VCO(2)) during
      anesthesia and the noninvasive detection of metabolic upset (e.g., onset of
      anaerobic metabolism) and critical events (e.g., pulmonary embolism).
      IMPLICATIONS: A new clinical bymixer (inline mixing chamber) provides a fast
      response and accurate measurements of mixed expired gas fractions in the
      anesthesia circle circuit. A novel parallel design facilitates adjustable
      response, easy cleaning, and construction from standard airway circuit
      components. The new clinical bymixer may facilitate widespread introduction of
      indirect calorimetry during anesthesia.

PMID- 14570660
TI  - Possible overestimation of indocyanine green-derived plasma volume early after
      induction of anesthesia with propofol/fentanyl.
AB  - Apparently large plasma volumes derived by indocyanine green (PV-ICG) have been
      determined in the initial period after induction of anesthesia. We tested the
      hypothesis that possible overestimation of PV-ICG occurs shortly after anesthetic
      induction. Anesthesia was induced in 13 patients with fentanyl bolus 2 microg/kg
      and propofol infusion 0.5 mg x kg(-1) x min(-1) IV until patients lost
      consciousness and was then maintained with a propofol infusion. PV-ICG and the
      initial distribution volume of glucose (IDVG) were assessed at 15 min before and
      at 15 min after anesthetic induction. Plasma ICG and glucose concentrations were
      measured from serial blood samples taken before and through 7 min after injection
      of ICG 25 mg and glucose 5 g. PV-ICG and IDVG were calculated using a one
      compartment model. PV-ICG was significantly increased by an average of 15.3%
      after induction, from 2.29 +/- 0.38 (SD) L to 2.64 +/- 0.31 L (P < 0.001). The
      mean hematocrit (Hct), concentrations of hemoglobin (Hb), and total plasma
      proteins at postinduction decreased compared with those at preinduction by 2.9%,
      2.2%, and 2.3%, respectively (P < 0.05). Percentile increase in plasma volume
      calculated from Hb and Hct before and after induction was 4%. Consequently, an
      11% overestimation in PV-ICG was observed. IDVG remained unchanged. Therefore,
      the ratio of PV-ICG/IDVG increased from 0.40 +/- 0.05 before induction to 0.48 +/
      0.06 after induction (P < 0.01). These results validate the hypothesis that
      possible overestimation of PV-ICG occurs during a definable period of time after
      propofol anesthetic induction. The present results also support the PV-ICG/IDVG
      ratio as a measure of possible overestimation of PV-ICG or fluid redistribution
      from the central to the peripheral tissues. IMPLICATIONS: An approximate 11%
      overestimation in indocyanine green derived plasma volume was observed after
      induction of anesthesia using propofol and fentanyl. Simultaneous measurement of
      the initial distribution volume of glucose may help investigate the presence of
      overestimation in indocyanine green derived plasma volume.

PMID- 14570661
TI  - The site of action of epidural fentanyl in humans: the difference between
      infusion and bolus administration.
AB  - Most published studies suggesting that epidural fentanyl acts predominantly at
      spinal sites administered the drug as a bolus injection, whereas most studies
      suggesting that it acts predominantly at supraspinal sites administered the drug
      as an infusion. In this study we tested the hypothesis that the mode of
      administration (bolus versus infusion) of epidural fentanyl determines its site
      of action. Ten healthy volunteers were enrolled in this randomized, double
      blinded, cross-over study. On separate study days fentanyl was administered into
      the epidural space as a bolus (0.03 mg followed by 0.1 mg 210 min later) and as
      an infusion (0.03 mg/h followed by 0.1 mg/hr 210 min later for 200 min). Using a
      thermal and electrical experimental pain model, the heat ( degrees C) and
      electrical current (mA) causing maximum tolerable pain were assessed repetitively
      over a period of 420 min. The analgesic efficacy measures were obtained at a
      lumbar and a cranial dermatome. Plasma fentanyl concentrations were determined
      throughout the study. Epidural bolus administration of fentanyl resulted in
      segmental analgesia (leg > head), whereas the epidural infusion of fentanyl
      produced nonsegmental analgesia (leg = head). There was a significant linear
      relationship between the analgesic effect and the plasma concentration of
      fentanyl for the epidural infusion but not for the epidural bolus administration
      of fentanyl. These findings support our hypothesis and might explain the apparent
      conflict in the literature regarding the site of action of epidural fentanyl.
      IMPLICATIONS: In an experimental pain study in volunteers, epidural fentanyl
      caused segmental analgesia when administered as a bolus and nonsegmental systemic
      analgesia when administered as a continuous infusion. This finding may help
      resolve the long-standing controversy surrounding the site of action of epidural
      fentanyl.

PMID- 14570662
TI  - The site of action of epidural fentanyl infusions in the presence of local
      anesthetics: a minimum local analgesic concentration infusion study in
      nulliparous labor.
AB  - We have previously demonstrated that continuous epidural infusions of fentanyl
      without local anesthetics elicit analgesia by a systemic mechanism. In this
      study, we examined the hypothesis that, in the presence of epidural bupivacaine,
      continuous infusions of epidural fentanyl elicit analgesia by a spinal mechanism.
      Forty-eight nulliparous women in active labor participated in this prospective,
      randomized, double-blinded study. Women received lumbar epidural analgesia with
      20-30 mL bupivacaine 0.125% until pain free. Subjects were then randomized to
      either IV or epidural (EPI) fentanyl infusion groups. Each infusion delivered
      fentanyl 30 microg/h. All women received an epidural infusion of bupivacaine at a
      rate of 20 mL/h, the concentration of which was determined by the response of the
      previous woman in the same group to the analgesic regimen used. Unlike previous
      studies that assessed the minimum local analgesic concentration (MLAC) for bolus
      administration at the initiation of analgesia, this study assessed MLAC(infusion)
      for the maintenance of analgesia throughout the first stage of labor.
      MLAC(infusion) was determined using the up-down sequential analysis described by
      Dixon and Massey. The MLAC(infusion) of epidural bupivacaine was 0.063% (95%
      confidence interval, 0.058-0.068) and 0.019% (95% confidence interval, 0.000
      0.038) in the IV and EPI groups respectively. A continuous infusion of fentanyl
      was more than three times as potent when administered by the epidural than by the
      IV route. This marked increase in potency for the epidural route is highly
      suggestive for a predominantly spinal mechanism of action for infused epidural
      fentanyl under the conditions of this study. IMPLICATIONS: This study determined
      the median effective concentration for epidural infusions of bupivacaine during
      labor analgesia. Coadministered epidural fentanyl infusions were more than three
      times more potent than IV fentanyl infusions, suggesting a predominantly spinal
      mechanism of opioid action under these study conditions.

PMID- 14570663
TI  - Spinal mechanisms contribute to analgesia produced by epidural sufentanil
      combined with bupivacaine for postoperative analgesia.
AB  - When used alone, lipid-soluble epidural opioids are thought to produce analgesia
      supraspinally via systemic absorption. However, spinal opioids and local
      anesthetics have been shown to act synergistically at the spinal level in animal
      studies. We, therefore, tested the hypothesis that sufentanil requirements will
      be less when given epidurally than IV in patients simultaneously given epidural
      bupivacaine after major abdominal surgery. Forty patients were anesthetized with
      isoflurane and epidural bupivacaine for major abdominal surgery. After surgery,
      each was given a continuous epidural infusion of bupivacaine at a rate of 5 mg/h
      and sufentanil patient-controlled analgesia (PCA). In a randomized, double
      blinded fashion, the sufentanil was given either epidurally or IV. PCA settings
      were the same in each group. For 60 hrs after surgery, the following variables
      were measured: pain scores at rest, during mobilization, and during coughing;
      extension of sensory block; side effects; and sufentanil consumption. Pain
      scores, extension of sensory block, and the incidence of side effects did not
      differ between the two groups. Consumption of sufentanil in the epidural group
      was half that of the IV group (48 h after surgery: 107 +/- 57 microg versus 207
      +/- 100 microg for the epidural and IV groups, respectively; P < 0.05). We
      conclude that spinal mechanisms contribute to the analgesia produced by epidural
      sufentanil in combination with a local anesthetic. IMPLICATIONS: When combined
      with epidural bupivacaine, the sufentanil requirement was 50% less when given
      epidurally than IV. Epidural sufentanil thus appears to have a spinal mechanism
      of action.

PMID- 14570664
TI  - Intrathecal morphine for postoperative analgesia: a randomized, controlled, dose
      ranging study after hip and knee arthroplasty.
AB  - In this series, we examined analgesia and side effects of intrathecal morphine
      sulfate (ITMS) after hip and knee arthroplasty over a dose range of 0.0-0.3 mg.
      Eighty patients undergoing hip (n = 40) or knee (n = 40) arthroplasty were
      randomized to receive ITMS (0.0, 0.1, 0.2, or 0.3 mg). A patient-controlled
      analgesia (PCA) device provided free access to additional analgesics. Morphine
      use, pain relief, and side effects were recorded for 24 h. Data were analyzed
      with analysis of variance and linear regression. After hip arthroplasty, morphine
      use was less in patients receiving 0.1, 0.2, or 0.3 mg of ITMS than in control
      patients (P < 0.05). After knee arthroplasty, ITMS did not reduce postoperative
      morphine requirements. Nausea and vomiting and the incidence of oxygen saturation
      <93% were similar in all groups. Pruritus was more common after ITMS. Patients
      receiving 0.2 or 0.3 mg of ITMS were more satisfied with their pain control than
      those receiving 0.0 or 0.1 mg after both hip and knee arthroplasty. Analgesic
      needs are greater after knee arthroplasty than after hip arthroplasty. We
      conclude that combining small-dose (0.2 mg) ITMS with PCA morphine provides good
      to excellent pain control in most patients after total hip or knee arthroplasty.
      However, PCA morphine use was reduced by the addition of ITMS only after hip
      arthroplasty. IMPLICATIONS: This series examined the need for supplemental
      analgesics, the quality of analgesia, and the incidence of side effects with
      intrathecal morphine sulfate (ITMS) for analgesia after hip and knee
      arthroplasty. Analgesic needs are greater after knee arthroplasty than hip
      arthroplasty. Combining small-dose (0.2 mg) ITMS with standard doses of PCA
      morphine provided good to excellent pain control in most patients and reduced
      patient-controlled analgesia morphine use after hip, but not knee, arthroplasty.

PMID- 14570665
TI  - Mu-opioid receptor mRNA regulation during morphine tolerance in the rat
      peripheral nervous system.
AB  - In vivo data on opioid receptor mRNA regulation after agonist exposure in the
      peripheral nervous system are lacking. Therefore, we studied the impact of
      morphine treatment on the regulation of mu-opioid receptor mRNA during behavioral
      signs of tolerance in rat peripheral sensory ganglia. Nineteen rats were treated
      in 2 groups with either morphine (10 mg/kg subcutaneously) or saline over 4 days,
      and a subset of rats received naloxone on the fifth day followed by either
      morphine injection on the sixth day or death to obtain dorsal root ganglia for
      mRNA analysis. Animals were tested on the hot plate during treatment days. To
      assess the levels of mu-opioid receptor mRNA, quantitative reverse transcriptase
      polymerase chain reaction (RT-PCR) was used with the co-amplification of the
      "housekeeping" gene cyclophilin as internal control. Morphine treatment over 4
      days induced tolerance as reflected on the hot-plate test by a significant
      reduction of paw-withdrawal latency from 242% to 99% above baseline. Using RT-PCR
      we demonstrated a down-regulation of mu-opioid receptor mRNA by 62% after
      morphine exposure (P < 0.05). After acute withdrawal of morphine from the mu
      receptor by naloxone, the mu-opioid receptor mRNA levels in the dorsal root
      ganglia were restored to control levels within 24 h and the paw-withdrawal
      latency also returned to 280% above control. These data suggest that the
      peripheral nervous system may be an important site of opioid tolerance
      development. IMPLICATIONS: The peripheral nervous system is a possible site of
      opioid receptor tolerance. We show the development of behavioral tolerance and mu
      opioid receptor mRNA down-regulation in the dorsal root ganglia in rats after
      chronic morphine treatment. Both this mRNA down-regulation and behavioral
      tolerance reverse after 24 h of naloxone treatment.

PMID- 14570666
TI  - Women experience more pain and require more morphine than men to achieve a
      similar degree of analgesia.
AB  - Sex differences in pain perception and in response to opioids have been
      described, but the findings are inconsistent. We sought to determine the effect
      of sex on pain perception, morphine consumption, and morphine analgesia after
      surgery. We designed a prospective cohort study and included 423 women and 277
      men who emerged from general anesthesia after surgical procedures and who
      reported pain intensity of >or=5 on the 0-10 numeric rating scale (NRS). We
      administered 2.5 mg of morphine IV every 10 min until the pain intensity was
      <or=4 of 10. Every 10 min, patients rated their pain on the NRS and indicated the
      degree of pain relief on a 5-point Likert scale. After adjustment for type of
      operation and age, we found that women had more intense pain and had larger
      morphine consumption than men. The difference in NRS pain intensity was 0.4 U
      (95% confidence interval, 0.1-0.6 U). Women required 0.03 mg/kg more morphine
      than men (95% confidence interval, 0.02-0.04 mg/kg). We conclude that women have
      more intense pain and require 30% more morphine to achieve a similar degree of
      analgesia compared with men. Clinicians should anticipate the differences in
      opioid requirement to avoid undertreatment of pain in women. IMPLICATIONS: The
      effect of sex on opioid response is not clear. To determine the effect of sex on
      morphine consumption and morphine analgesia, we designed a cohort study. We found
      that women had more intense pain and required 30% more morphine to achieve a
      similar degree of analgesia compared with men.

PMID- 14570667
TI  - Electrical stimulation of auricular acupuncture points is more effective than
      conventional manual auricular acupuncture in chronic cervical pain: a pilot
      study.
AB  - In this prospective, randomized, double-blinded, controlled study, we tested the
      hypothesis that auricular electroacupuncture relieves pain more effectively than
      conventional manual auricular acupuncture. We studied 21 chronic cervical pain
      patients without radicular symptoms with insufficient pain relief (visual
      analogue scale >5) treated with standardized analgesic therapy. All patients
      received disposable acupuncture needles on the dominant side on the following
      acupuncture points: cervical spine, shen men, and cushion. In 10 patients,
      needles were continuously stimulated (2-mA constant current, 1 Hz monophasic) by
      using the electrical point stimulation device P-STIM. In 11 control patients, no
      electrical stimulation was administered. All needles were withdrawn 48 h after
      insertion. Acupuncture was performed once a week for 6 wk. Patients had to
      complete a questionnaire assessing pain intensity, psychological well-being,
      activity, sleep, and demand for rescue medication (lornoxicam and tramadol). The
      reduction in pain scores was significant in the electrical acupuncture group.
      Similarly, psychological well-being, activity, and sleep were significantly
      improved in patients receiving electrical acupuncture, and consumption of rescue
      medication was significantly less. These results demonstrate that continuous
      electrical stimulation of auricular acupuncture points by using the new point
      stimulation device P-STIM improves the treatment of chronic cervical pain in an
      outpatient population. IMPLICATIONS: Continuous electrical stimulation of
      auricular acupuncture points by using the new point stimulation device P-STIM
      significantly decreases pain intensity and significantly improves psychological
      well-being, activity, and sleep in chronic cervical pain patients.

PMID- 14570668
TI  - Does a single intravenous injection of the 5HT3 receptor antagonist ondansetron
      have an analgesic effect in neuropathic pain? A double-blinded, placebo
      controlled cross-over study.
AB  - Neurokinin-1-expressing neurones in lamina I to III of the spinal cord are
      intimately involved in the regulation of ascending and spino-bulbal pathways that
      regulate excitatory transmission. In experimental animals, ablation of these
      neurones reduces the responses to a variety of nociceptive stimuli. Furthermore,
      in animals, spinal application of the selective 5HT3 receptor antagonist
      ondansetron mimics these effects, indicating that 5HT3 receptors play a
      pronociceptive role and mediate descending excitatory controls that allow spinal
      neurones to fully code peripheral stimuli. In this study, we examined the
      potential analgesic effect of a single IV injection of ondansetron in humans with
      chronic neuropathic pain. Each consenting subject received a single IV injection
      of 8 mg ondansetron and placebo in varying order at least 1 wk apart with pain
      scores being recorded for the 48 h preceding and after each injection. Pain
      scores were significantly reduced 2 h after ondansetron injection (but at no
      other time point). This suggests that ondansetron can have an analgesic effect in
      neuropathic pain. Side effects were minor and infrequent. IMPLICATIONS: The
      selective 5HT3 receptor antagonist ondansetron, currently used as an antiemetic,
      may also have analgesic properties. Side effects with a single IV injection are
      infrequent and usually mild.

PMID- 14570669
TI  - Educational or organizational approach: which is more effective in changing blood
      sampling habits?
AB  - Diagnostic blood loss is a recognized issue during the delivery of intensive care
      services. We designed this study to compare the effects of educational versus
      organizational approaches to reduce daily diagnostic blood loss in intensive care
      patients. First, as an educational approach, physicians on two wards were
      repeatedly informed about the importance of diagnostic blood loss and that 1.0
      1.5 mL is sufficient for blood gas analysis. Second, as an organizational
      approach, 3-mL syringes were replaced by 2-mL syringes. Measurements after both
      periods were compared with a control group. The amount of drawn/discarded blood
      of 320 samples was measured in each group after the 2 interventions. Compared
      with the control group, the educational program reduced the amount of
      drawn/discarded blood in one ward, but not the other. After the organizational
      change, the amount of drawn/discarded blood was reduced in both wards.
      Additionally, because of the smaller costs of 2-mL syringes, implementation of 2
      mL syringes saved US dollars 30800/yr in our hospital. In conclusion, our study
      shows that an educational program seems less effective in influencing physician
      behavior than organizational changes. Therefore, organizational changes should be
      favored over educational approaches whenever possible. IMPLICATIONS:
      Organizational change is more effective than educational programs to reduce
      diagnostic blood loss. Organizational implementation of smaller syringes reduces
      the amount of discarded blood and can save money.

PMID- 14570670
TI  - The use and effectiveness of electrocardiographic telemetry monitoring in a
      community hospital general care setting.
AB  - The purpose of this study was to determine if rates of telemetry events differ
      between patients whose monitoring is appropriately "indicated" versus "not
      indicated" by systematically applying rigorous criteria for appropriateness of
      electrocardiogram (ECG) telemetry usage. We performed a retrospective cohort
      study on 1097 telemetry admissions between January 1, 2000 and March 31, 2000. A
      convenience sample of 218 patients generated 236 telemetry admissions. One
      hundred-sixty-two arrhythmic events were detected during 400 "indicated"
      telemetry days. Nine arrhythmic events were detected during 345 "not indicated"
      telemetry days. The relative rate for arrhythmic events was significantly
      different, at P < 0.0001, with the incidence rate ratio of 15 indicating a very
      large effect size. Consequently, current use of ECG telemetry may not be optimal,
      and a prospective analysis of the application of rigorous indications for ECG
      telemetry needs to be undertaken. IMPLICATIONS: The application of standard
      criteria to electrocardiogram telemetry admissions found that the majority of
      abnormal heart rhythms were found when patients met appropriate criteria.

PMID- 14570671
TI  - A silicone-based wire-reinforced tracheal tube with a hemispherical bevel reduces
      nasal morbidity for nasotracheal intubation.
AB  - We tested the hypothesis that a silicone-based wire-reinforced tracheal tube with
      a hemispherical bevel is superior to a polyvinyl chloride (PVC)-based precurved
      tube with a conventional diagonal bevel for nasotracheal intubation. Eighty
      anesthetized paralyzed adults (ASA physical status I-II) requiring nasotracheal
      intubation for tonsillectomy were randomly allocated into two equal-sized groups
      for airway management with the silicone tracheal tube or PVC tracheal tube.
      Intubation was subdivided into three phases: 1). passage through the nose into
      the pharynx, 2). laryngoscope-guided passage into the glottic inlet, and 3).
      laryngoscope-guided passage into the trachea. A specific sequence of airway
      maneuvers was followed at each stage if it was unsuccessful. The number of
      attempts and intubation time were documented by an unblinded observer. The
      frequency of epistaxis and postoperative nasal complications was documented by
      blinded observers. There were no intubation failures. The number of attempts at
      pharyngeal (47 versus 56; P = 0.04) and tracheal (43 versus 55; P = 0.005)
      placement was smaller for the silicone tracheal tube, but the number of attempts
      at glottic placement was more (72 versus 49; P < 0.0001). Intubation time was
      similar. The frequency (32% versus 80%; P < 0.0001) and severity of epistaxis
      were less for the silicone tracheal tube. The total number of postoperative nasal
      symptoms was smaller for the silicone tracheal tube (10 versus 21; P < 0.05). We
      conclude that the pharyngeal and tracheal placement phases of nasotracheal
      intubation require fewer attempts with the silicone tracheal tube than the PVC
      tracheal tube but that the glottic placement phase requires more attempts. Nasal
      morbidity is less common with the silicone tracheal tube. IMPLICATIONS: The
      pharyngeal and tracheal placement phases of nasotracheal intubation require fewer
      attempts with a silicone-based wire-reinforced tracheal tube with a hemispherical
      bevel than with a polyvinyl chloride-based precurved tracheal tube with a
      conventional diagonal bevel, but the glottic placement phase requires more
      attempts. Nasal morbidity is less common with the silicone tracheal tube.

PMID- 14570672
TI  - Peroxynitrite decreases dopamine's vasoconstrictive activity.
AB  - Peroxynitrite (ONOO(-1)) reacts with dopamine to form an oxidized derivative. To
      investigate the vasoconstrictive activity of this derivative, we performed
      functional examinations with dopamine treated with ONOO(-1) or 3
      morpholinosydonimine-N-ethyl-carbamine (SIN-1; an ONOO(-1) producer) on isolated
      strips of rat thoracic aorta. To exclude the direct effect of ONOO(-1), the
      strips were pretreated with methylene blue, a guanylyl cyclase inhibitor.
      Dopamine induced concentration-dependent contraction, but dopamine pretreated
      with ONOO(-1) decreased the contraction in an ONOO(-1)-concentration-dependent
      manner. Both maximum contractions and 50% effective concentration values for
      dopamine-induced vasocontraction were significantly decreased by pretreatment
      with ONOO(-1). Dopamine incubated with SIN-1 also decreased the contraction, the
      decrease being dependent on the incubation time. ONOO(-1) formation is a favored
      reaction and occurs easily when cellular production of both nitric oxide and
      superoxide increases, as in septic shock. These results may, at least in part,
      account for dopamine's limitation as a vasoconstrictor in septic shock.
      IMPLICATIONS: Peroxynitrite (ONOO(-1)) reacts with dopamine to form an oxidized
      derivative. We investigated the vasoconstrictive activity of this derivative with
      functional examinations using rat thoracic aorta and found the activity
      decreased. As ONOO(-1) formation increases in septic shock, our results may
      account for dopamine's limitation as a vasoconstrictor in septic shock.

PMID- 14570673
TI  - Intermittent nitric oxide combined with intravenous dipyridamole in a piglet
      model of acute pulmonary hypertension.
AB  - Continuous administration of inhaled nitric oxide is now widely used as a potent
      and selective pulmonary vasodilator. We have evaluated the effects of IV
      dipyridamole, a cyclic guanosine monophosphate (cGMP) phosphodiesterase
      inhibitor, on the magnitude and duration of action of inhaled nitric oxide (NO)
      mediated pulmonary vasodilation. We hypothesized that inhibition of cGMP
      degradation could augment and prolong the pulmonary vasodilating effects of NO
      and allow for intermittent NO inhalation. In eight anesthetized and mechanically
      ventilated piglets, IV U-46619, a thromboxane A(2) analog, was used to induce
      pulmonary hypertension. The effects of 2, 5, and 10 ppm of NO, delivered during 4
      min for each concentration and followed by a 10-min NO-free interval after each
      NO concentration, were evaluated without and with dipyridamole. Pulmonary
      vascular resistance decreased from 825 +/- 49 dynes. s. cm(-5) (U-46619) to 533
      +/- 48 dynes. s. cm(-5) (10 ppm NO) (P < 0.05 versus U-46619) and 396 +/- 42
      dynes. s. cm(-5) (dipyridamole 10 microg kg-1x min-1 and 10 ppm NO) (P <0.05
      versus NO), and cardiac output increased from 1.93 +/- 0.09 L/min to 2.03 +/-
      0.13 L/min and 2.60 +/- 0.30 L/min (P < 0.05 versus NO). Mean arterial blood
      pressure decreased from 90 +/- 5 mm Hg (10 ppm NO) to 75 +/- 3 mm Hg
      (dipyridamole plus 10 ppm NO) (P < 0.01). The pulmonary vasodilation obtained
      with NO alone could be prolonged from 12 to 42 min when inhaled NO was combined
      with IV dipyridamole, accounting for a time-weighted reduction in NO exposure by
      72%. We conclude that dipyridamole augments the effects of NO on right
      ventricular afterload, allows for intermittent NO inhalation, and can
      significantly reduce exposure to NO. IMPLICATIONS: IV dipyridamole prolongs the
      action of inhaled nitric oxide (NO) in a piglet model of acute pulmonary
      hypertension. Intermittent NO inhalation combined with IV dipyridamole decreases
      pulmonary artery pressure for a prolonged period of time and reduces exposure to
      NO.

PMID- 14570674
TI  - A comparison of cerebrospinal fluid and plasma urotensin II concentrations in
      normotensive and hypertensive patients undergoing urological surgery during
      spinal anesthesia: a pilot study.
AB  - Urotensin II is a novel endogenous vasoconstrictor. There are no data describing
      cerebrospinal fluid (CSF) concentrations in humans. Therefore, in this study, we
      aimed to quantify and compare plasma and CSF urotensin II concentrations in
      patients with essential hypertension and matched controls. Twenty male patients
      (10 receiving >6 mo of treatment for essential hypertension and 10 normotensive
      controls scheduled to undergo urological surgery under spinal anesthesia) were
      recruited into this single-blinded cohort study. Plasma and CSF urotensin II
      concentrations were measured by radioimmunoassay, along with mean arterial blood
      pressure (MAP), before admission, on the day of admission, and immediately before
      anesthesia. CSF and plasma urotensin II concentrations were low. Median (range)
      values in CSF for all 20 patients were significantly lower than plasma by
      approximately 15% (19.0 pg/mL [10.6-24.9 pg/mL] compared with 22.3 pg/mL [17.7
      28.4 pg/mL]; P = 0.004). There were no significant differences between
      normotensive and hypertensive patients in either CSF or plasma concentrations.
      However, there was a significant positive correlation between average MAP and CSF
      urotensin II concentrations (r(2) = 0.44; P = 0.036) in the hypertensive group.
      IMPLICATIONS: Urotensin II is the most potent known endogenous human
      vasoconstrictor. In this pilot study, we report for the first time that
      cerebrospinal fluid levels are smaller than plasma levels and that there may be
      some association with increased blood pressure.

PMID- 14570675
TI  - Reduced duration of intrathecal sufentanil analgesia in laboring cocaine users.
AB  - On the basis of our previous clinical experience, we hypothesized in this study
      that the duration and/or quality of labor analgesia produced by intrathecal
      sufentanil was less in cocaine-abusing parturients compared with nonabusing
      parturients. Ten micro g of sufentanil was given intrathecally as part of a
      combined spinal-epidural (CSE) technique to two groups of laboring parturients:
      1). those whose urine tested positive for cocaine (cocaine group), and 2). those
      whose urine tested negative for cocaine (control group). The epidural catheter
      was not injected with local anesthetic until the patient requested additional
      pain relief. The time from injection of intrathecal sufentanil until patient
      request for additional pain relief was defined as duration of analgesia. Baseline
      visual analog pain score (VAPS) and cervical dilation were measured before the
      CSE was performed. After injection of intrathecal sufentanil, VAPS was recorded
      at specific intervals. Cervical dilation was again documented when the patient
      requested additional analgesia. We found that both groups reported high baseline
      VAPS and a marked decrease in VAPS after injection of sufentanil that did not
      differ between groups. Geometric mean duration of pain relief with adjustment for
      cervical dilation was 87 min in the cocaine group compared with 139 min in the
      control group (P = 0.019). All patients experienced itching. We conclude that
      intrathecal sufentanil produces a similar quality but shorter duration of
      analgesia in cocaine-abusing parturients compared with nonabusing parturients.
      IMPLICATIONS: Intrathecal sufentanil administered as part of a combined spinal
      epidural technique produces similar quality but reduced duration of labor
      analgesia in cocaine-abusing parturients compared with nonabusing parturients.

PMID- 14570676
TI  - The relative motor blocking potencies of bupivacaine and levobupivacaine in
      labor.
AB  - Minimum local analgesic concentrations (MLAC) have been used to determine the
      epidural analgesic potencies of bupivacaine and its levo- counterpart. There are
      no reports of the motor blocking potencies of these drugs. In this study we
      sought to determine the motor block MLAC of both drugs and determine the relative
      potency ratio. Sixty ASA physical status I-II parturients were randomized. The
      first woman in each group received 0.25% wt/vol. Up-down sequential allocation
      was used to determine subsequent concentrations at a testing interval of 0.025%
      wt/vol. Effective motor block was defined as a Bromage score <4 within 30 min.
      The up-down sequences were analyzed with the Dixon and Massey method and probit
      regression. Two-sided P < 0.05 defined significance. The motor block MLAC for
      bupivacaine was 0.27% wt/vol (95% confidence interval [CI], 0.25-0.30) and for
      levobupivacaine was 0.31% wt/vol (95% CI, 0.29-0.34) (P = 0.024), with a
      levobupivacaine/bupivacaine potency ratio of 0.87 (95% CI, 0.77-0.98). This is
      the first study to estimate the motor-blocking potency ratio of bupivacaine and
      levobupivacaine in labor. This study demonstrates that the S-enantiomer of
      bupivacaine is less potent at motor block than the racemate. IMPLICATIONS: We
      estimated the motor-blocking potency ratio of bupivacaine and levobupivacaine in
      labor and demonstrated that the S-enantiomer of bupivacaine is less potent at
      motor block than the racemate.

PMID- 14570677
TI  - Ultrasound-guided supraclavicular brachial plexus block.
AB  - In this study, we evaluated state-of-the-art ultrasound technology for
      supraclavicular brachial plexus blocks in 40 outpatients. Ultrasound imaging was
      used to identify the brachial plexus before the block, guide the block needle to
      reach target nerves, and visualize the pattern of local anesthetic spread. Needle
      position was further confirmed by nerve stimulation before injection. The block
      technique we describe aligned the needle path with the ultrasound beam. The block
      was successful after one attempt in 95% of the cases, with one failure
      attributable to subcutaneous injection and one to partial intravascular
      injection. Pneumothorax did not occur. Our preliminary data suggest that a high
      resolution ultrasound probe can reliably identify the brachial plexus and its
      neighboring structures in the supraclavicular region. The technique of real-time
      guidance during needle advancement can quickly localize nerves. Distinct patterns
      of local anesthetic spread observed on ultrasound can further confirm accurate
      needle location. IMPLICATIONS: Real-time ultrasound imaging during
      supraclavicular brachial plexus blocks can facilitate nerve localization and
      needle placement and examine the pattern of local anesthetic spread.

PMID- 14570678
TI  - Ultrasound guidance speeds execution and improves the quality of supraclavicular
      block.
AB  - In this prospective study, we assessed the quality, safety, and execution time of
      supraclavicular block of the brachial plexus using ultrasonic guidance and
      neurostimulation compared with a supraclavicular technique that used anatomical
      landmarks and neurostimulation. It was hypothesized that ultrasonic guidance
      would increase the proportion of successful blocks, decrease block execution
      time, and reduce the incidence of complications such as pneumothorax and
      neuropathy. Eighty patients were randomized into two groups of 40, Group US
      (supraclavicular block guided in real time by a two-dimensional ultrasonic image,
      with neurostimulator confirmation of correct needle position) and Group NS
      (supraclavicular block using the subclavian perivascular approach, also with
      neurostimulator confirmation). Blocks were performed using bupivacaine 0.5% and
      lidocaine 2% (1:1 vol) with epinephrine 1:200000 as the anesthetic mixture. The
      onset of motor and sensory block for the musculocutaneous, median, radial, and
      ulnar nerves was evaluated over a 30 min period. At 30 min 95% of patients in
      Group US and 85% of patients in Group NS had a partial or complete sensory block
      of all nerve territories (P = 0.13) and 55% of patients in Group US and 65% of
      patients in Group NS had a complete block of all nerve territories (P = 0.25).
      Surgical anesthesia without supplementation was achieved in 85% of patients in
      Group US and 78% of patients in Group NS (P = 0.28). No patient in Group US and
      8% of patients in Group NS required general anesthesia (P = 0.12). The quality of
      ulnar block was significantly inferior to the quality of block in other nerve
      territories in Group NS, but not in Group US; the quality of ulnar block was not
      significantly different between Groups NS and US. The block was performed in an
      average of 9.8 min in Group NS and 5.0 min in Group US (P = 0.0001). No major
      complication occurred in either group. We conclude that ultrasound-guided
      neurostimulator-confirmed supraclavicular block is more rapidly performed and
      provides a more complete block than supraclavicular block using anatomic
      landmarks and neurostimulator confirmation. IMPLICATIONS: Ultrasound-guided
      neurostimulator-confirmed supraclavicular block is more rapidly performed and
      provides a block of better quality than supraclavicular block using anatomic
      landmarks and neurostimulator confirmation.

PMID- 14570679
TI  - Tensile strength of 19- and 20-gauge arrow epidural catheters.
AB  - There are no data about the mechanical properties of the 20-gauge reinforced
      Arrow epidural catheter, which has a similar design to the 19-gauge reinforced
      Arrow catheter. In this study, we compared the mechanical properties of 19- and
      20-gauge Arrow epidural catheters at 22 degrees C and 37 degrees C. The distal 12
      cm of each catheter was suspended in an enclosed chamber maintained at either 22
      degrees C or 37 degrees C. A pair of forceps was applied to each catheter 5 cm
      from the distal end (fixed site). Another pair of forceps was applied 15 cm from
      the catheter tip (traction site). The catheter was pulled. At 22 degrees C, the
      mean fracture force was 2.24 kg (range, 1.96 - 2.41 kg) for 5 19-gauge catheters
      and 2.17 kg (range, 2.04-2.41 kg) for 5 20-gauge catheters. At 37 degrees C, the
      mean force was 1.98 kg (range 1.84- 2.15 kg) for 5 19-gauge catheters and 1.99 kg
      (range, 1.81-2.09 kg) for 5 20-gauge catheters. There were no significant
      differences in tensile strength between the two different gauge catheters at
      either temperature. All the 19-gauge catheters fractured at the same "fixed site"
      at both temperatures. All the 20-gauge catheters elongated at the "fixed site"
      but fractured at the "traction site." We conclude that using the smaller-gauge
      catheter (20-gauge) is not associated with a more frequent rate of fracture.
      IMPLICATIONS: The 20-gauge Arrow epidural catheters had similar tensile strengths
      as the 19-gauge epidural catheters but fractured at the traction site rather than
      at the fixed site. Thus, the 20-gauge Arrow catheter may be a reasonable
      alternative to the 19-gauge Arrow catheter.

PMID- 14570680
TI  - Transient postoperative neurologic deficit after lumbar laminectomy.
AB  - New neurological deficit after spinal surgery is a rare complication that
      requires a quick diagnostic and therapeutic approach to reduce the risk of
      permanent neurological disabilities. We report a patient who presented with
      transient neurologic deficit after surgery for lumbar disk herniation resulting
      from bupivacaine diffusion to either the epidural or the subarachnoid space
      occurring after the anesthetic infiltration of the surgical wound. Early magnetic
      resonance imaging excluded more serious causes of such neurological deterioration
      after lumbar laminectomy. This complication should be considered by the
      anesthesiologist in the differential diagnosis of neurological deficits after
      operations on the lumbar spine. IMPLICATIONS: We report a patient who presented
      in the recovery room with a transient neurologic deficit likely resulting from
      surgical injection of local anesthetic after lumbar laminectomy. This uncommon
      complication should be considered in the differential diagnosis of postoperative
      neurological deficits. Early magnetic resonance imaging excluded more serious
      causes of this complication.

PMID- 14570681
TI  - Controlled hypotension and minimal inflation pressure: a new approach for
      pneumatic tourniquet application in upper limb surgery.
AB  - Minimal inflation pressures are recommended for limb surgery to eliminate
      complications attributable to high inflation pressures with the pneumatic
      tourniquets. We applied controlled hypotension and a minimal inflation pressure
      (CHAMIP) technique to provide a bloodless surgical field. Thirty-six patients
      scheduled for upper extremity surgery were randomized equally to receive either
      normotensive anesthesia and conventional inflation pressures or controlled
      hypotension (systolic arterial blood pressure of 80-100 mm Hg and mean arterial
      blood pressure >60 mm Hg) and minimum inflation pressures. Anesthesia was induced
      with propofol IV bolus and remifentanil IV continuous infusion and maintained
      with propofol and remifentanil IV continuous infusion. To determine the minimal
      inflation pressure, the digital plethysmograph was applied to the second finger
      at the side of the operation and the tourniquet was inflated slowly until the
      arterial pulsations disappeared on the oscilloscope. A bloodless surgical field
      was obtained in almost all patients, even though systolic arterial blood
      pressures (100-138 mm Hg versus 80-100 mm Hg) and applied tourniquet inflation
      pressures (270 mm Hg versus 110-140 mm Hg) were significantly lower in the
      hypotensive group. No complications associated with controlled hypotension were
      encountered. In conclusion, CHAMIP may be a safe and reliable method for upper
      extremity surgery performed with pneumatic tourniquets. IMPLICATIONS: Pneumatic
      tourniquets are associated with adverse effects resulting from high inflation
      pressures. Therefore, minimal inflation pressures are recommended in extremity
      surgery. To reach real minimal inflation pressure the patient's blood pressure
      must be reduced. We used controlled hypotension with remifentanil and propofol to
      reach minimal inflation pressures.

PMID- 14570682
TI  - Oxygenation using tidal volume breathing after maximal exhalation.
AB  - We compared, in volunteers, the oxygenation achieved by tidal volume breathing
      (TVB) over a 3-min period after maximal exhalation with that achieved by TVB
      alone. Twenty-three healthy volunteers underwent the two breathing techniques in
      a randomized order. A circle absorber system with an oxygen flow of 10 L/min was
      used. The end-expiratory oxygen concentration (EEO(2)) was monitored at 15-s
      intervals up to 3 min. TVB after maximal exhalation produced EEO(2) values of 68%
      +/- 5%, 75% +/- 5%, and 79% +/- 4% at 30, 45, and 60 s, respectively, which were
      significantly larger (P < 0.05) than the corresponding values obtained with TVB
      alone (58% +/- 5%, 66% +/- 6%, and 71% +/- 5%, respectively). In both techniques,
      the EEO(2) increased exponentially, with time constants of 35 s during TVB after
      maximal exhalation versus 58 s during TVB without prior maximal exhalation. In
      conclusion, maximal exhalation before TVB can hasten preoxygenation by decreasing
      the nitrogen content of the functional residual capacity, with a consequent
      increase of EEO(2) to approximately 70% in 30 s and 80% in 60 s. IMPLICATIONS:
      Oxygenation by using maximal exhalation before tidal volume breathing produced a
      significantly faster increase in end-expiratory oxygen concentration than
      oxygenation with tidal volume breathing alone.

PMID- 14570683
TI  - Transurethral resection syndrome after bladder perforation.
AB  - The use of irrigating solutions is essential for distension of mucosal surfaces
      and visualization of the surgical field during resectoscopic resection of bladder
      tumors (TURBT). TURBT resection may be complicated with bladder perforation
      associated with intraperitoneal extravasation of irrigant fluid, which may rarely
      evolve in specific hydroelectrolyte imbalance characterized with hyponatremia,
      intravascular volume deficit, and renal impairment. We report four cases of TURBT
      syndrome during bladder surgery complicated by bladder perforation and discuss
      issues relevant to pathophysiology, diagnosis, and treatment of this rare
      condition.

PMID- 14570684
TI  - Anesthesia for corrective spinal surgery in a patient with Leigh's disease.
AB  - We report a case of anesthesia for posterior spinal fusion in a woman with
      Leigh's disease. This is a syndrome with a heterogeneous phenotype including
      ocular signs, motor signs, and respiratory disorder. It is associated with
      defects in the enzymes of the mitochondrial respiratory chain and central neural
      degeneration. Anesthesia is associated with worsening of the respiratory
      symptoms. Our patient underwent major spinal surgery as a palliative procedure.
      Her postoperative course was complicated by acute lung injury and sepsis. She
      ultimately failed a prolonged respiratory wean. Serial magnetic resonance imaging
      revealed a rapidly progressive necrosis of her brain stem and cervical spinal
      cord consistent with activation of her underlying Leigh's disease. This is the
      first report of spinal surgery in this patient group. It is also the first
      radiological demonstration of Leigh's disease reactivation in the postoperative
      period. Anesthesia and surgery are hazardous in this patient population, and
      respiratory symptoms make this a high-risk group. Surgery should only be
      undertaken with caution and after frank consent. Early postoperative imaging is
      recommended if there are respiratory complications. No drug prophylaxis has been
      shown to alter disease activation. IMPLICATIONS: Patients suffering from Leigh's
      disease are at high risk of serious postoperative respiratory morbidity. We
      present a case that demonstrates delayed respiratory complications and link this
      postoperative adverse outcome to aggressive reactivation of the underlying
      neurodegenerative condition.

PMID- 14570685
TI  - There should be a threshold dose for the FDA black-box warning on droperidol.

PMID- 14570686
TI  - Reviewing case reports and the droperidol warning: FDA response.

PMID- 14570687
TI  - Both a large and small thyromental distance can predict difficult intubation.

PMID- 14570688
TI  - Do we need to intubate the trachea 2 minutes after vecuronium 0.1 mg/kg in
      elective surgery?

PMID- 14570690
TI  - Latex allergy and cardiac surgery.

PMID- 14570689
TI  - Subhypnotic dose of droperidol may increase frequency of PONV after propofol
      anesthesia.

PMID- 14570691
TI  - Omission of muscle relaxants is another clinically available alternative in fast
      track cardiac anesthesia.

PMID- 14570692
TI  - Safety of levobupivacaine?

PMID- 14570693
TI  - Convincing effects of clonidine on neurohumoral withdrawal symptoms during
      antagonist-supported detoxification of opioid addicts.

PMID- 14570694
TI  - Epidural catheterization in general anesthesia.

PMID- 14570695
TI  - Endocarditis of a left ventricular assist device resulting in regurgitant flow.

PMID- 14570696
TI  - The importance of methodology.

PMID- 14570697
TI  - Muscle biopsy for malignant hyperthermia testing can be scheduled and performed
      in 6 weeks.

PMID- 14570698
TI  - Stanniocalcin-1, an inhibitor of macrophage chemotaxis and chemokinesis.
AB  - In macrophages, changes in intracellular calcium have been associated with
      activation of cellular processes that regulate cell adhesion and motility and are
      important for the response of macrophages to antigenic stimuli. The mammalian
      counterpart of the fish calcium-regulating hormone stanniocalcin-1 (STC1) is
      expressed in multiple organs including the thymus and spleen, and hence, we
      hypothesized that it may have a role in modulating the immune/inflammatory
      response. Using murine macrophage-like (RAW264.7) and human monoblast-like (U937)
      cells to study chemotaxis in vitro, we found that STC1 attenuated chemokinesis
      and diminished the chemotactic response to monocyte chemotactic protein-1 (MCP-1)
      and stromal cell-derived factor-1alpha. Consistent with these findings, STC1
      blunted the rise in intracellular calcium following MCP-1 stimulation in RAW264.7
      cells. In vivo studies suggested differential expression of STC1 in obstructed
      kidney and localization to macrophages. MCP-1 and STC1 transcripts were both
      upregulated following ureteric obstruction, suggesting a functional association
      between the two genes. Our data suggest a role for mammalian STC1 in modulating
      the immune/inflammatory response.

PMID- 14570699
TI  - Protein kinase C-epsilon modulates mitochondrial function and active Na+
      transport after oxidant injury in renal cells.
AB  - The aim of this study was to determine whether protein kinase C-epsilon (PKC
      epsilon) is involved in the repair of mitochondrial function and/or active Na+
      transport after oxidant injury in renal proximal tubular cells (RPTC). Sublethal
      injury was produced in primary cultures of RPTC using tert-butylhydroperoxide
      (TBHP), and the recovery of functions was examined. PKC-epsilon was activated
      three- to fivefold after injury. Active PKC-epsilon translocated to the
      mitochondria. Basal oxygen consumption (Qo2), uncoupled Qo2, and ATP production
      decreased 58, 60, and 41%, respectively, at 4 h and recovered by day 4 after
      injury. At 4 h, complex I-coupled respiration decreased 50% but complex II- and
      IV-coupled respirations were unchanged. Inhibition of PKC-epsilon translocation
      using a peptide selective inhibitor, PKC-epsilonV1-2, reduced decreases in basal
      and uncoupled Qo2 values and increased complex I-linked respiration in TBHP
      injured RPTC at 4 h of recovery. Furthermore, PKC-epsilonV1-2 prevented decreases
      in ATP production in injured RPTC. Na+-K+-ATPase activity and ouabain-sensitive
      86Rb+ uptake were decreased by 60 and 53%, respectively, at 4 h of recovery.
      Inhibition of PKC-epsilon activation prevented a decline in Na+-K+-ATPase
      activity and reduced decreases in ouabain-sensitive 86Rb+ uptake. We conclude
      that during early repair after oxidant injury in RPTC 1) PKC-epsilon is activated
      and translocated to mitochondria; 2) PKC-epsilon activation decreases
      mitochondrial respiration, electron transport rate, and ATP production by
      reducing complex I-linked respiration; and 3) PKC-epsilon mediates decreases in
      active Na+ transport and Na+-K+-ATPase activity. These data show that PKC-epsilon
      activation after oxidant injury in RPTC is involved in the decreases in
      mitochondrial function and active Na+ transport and that inhibition of PKC
      epsilon activation promotes the repair of these functions.

PMID- 14570701
TI  - Effect of glycogen synthase overexpression on insulin-stimulated muscle glucose
      uptake and storage.
AB  - Insulin-stimulated muscle glucose uptake is inversely associated with the muscle
      glycogen concentration. To investigate whether this association is a cause and
      effect relationship, we compared insulin-stimulated muscle glucose uptake in
      noncontracted and postcontracted muscle of GSL3-transgenic and wild-type mice.
      GSL3-transgenic mice overexpress a constitutively active form of glycogen
      synthase, which results in an abundant storage of muscle glycogen. Muscle
      contraction was elicited by in situ electrical stimulation of the sciatic nerve.
      Right gastrocnemii from GSL3-transgenic and wild-type mice were subjected to 30
      min of electrical stimulation followed by hindlimb perfusion of both hindlimbs.
      Thirty minutes of contraction significantly reduced muscle glycogen concentration
      in wild-type (49%) and transgenic (27%) mice, although transgenic mice retained
      168.8 +/- 20.5 micromol/g glycogen compared with 17.7 +/- 2.6 micromol/g glycogen
      for wild-type mice. Muscle of transgenic and wild-type mice demonstrated similar
      pre- (3.6 +/- 0.3 and 3.9 +/- 0.6 micromol.g(-1).h(-1) for transgenic and wild
      type, respectively) and postcontraction (7.9 +/- 0.4 and 7.0 +/- 0.4 micromol.g(
      1).h(-1) for transgenic and wild-type, respectively) insulin-stimulated glucose
      uptakes. However, the [14C]glucose incorporated into glycogen was greater in
      noncontracted (151%) and postcontracted (157%) transgenic muscle vs. muscle of
      corresponding wild-type mice. These results indicate that glycogen synthase
      activity is not rate limiting for insulin-stimulated glucose uptake in skeletal
      muscle and that the inverse relationship between muscle glycogen and insulin
      stimulated glucose uptake is an association, not a cause and effect relationship.

PMID- 14570700
TI  - Effects of acute bouts of running and swimming exercise on PGC-1alpha protein
      expression in rat epitrochlearis and soleus muscle.
AB  - The purpose of this study was to elucidate the mechanisms underlying low
      intensity exercise-induced peroxisome proliferator-activated receptor-gamma
      coactivator-1alpha (PGC-1alpha) protein expression in rat skeletal muscles. Rats
      (5-6 wk old) swam without a load and ran on the treadmill at a speed of 13 m/min,
      respectively, in two 3-h sessions separated by 45 min of rest. PGC-1alpha content
      in epitrochlearis muscle (EPI) was increased by 75 and 95%, immediately and 6 h
      after swimming, respectively, with no increase in PGC-1alpha content in the
      soleus (SOL). After running, PGC-1alpha content in EPI was unchanged, whereas a
      107% increase in PGC-1alpha content was observed in SOL 6 h after running.
      Furthermore, in EPI and SOL as well as other muscles (triceps, plantaris, red and
      white gastrocnemius), PGC-1alpha expression was enhanced concomitant with reduced
      glycogen postexercise, suggesting that expression of PGC-1alpha occurs in
      skeletal muscle recruited during exercise. PGC-1alpha content in EPI was
      increased after 18-h in vitro incubation with 0.5 mM 5-aminoimidazole-4
      carboxamide ribonucleoside (AICAR) and 4 mM caffeine. However, AICAR incubation
      did not affect PGC-1alpha content in the SOL, whereas caffeine incubation
      increased it. These results suggest that exercise-induced PGC-1alpha expression
      in skeletal muscle may be mediated by at least two exercise-induced signaling
      factors: AMPK activation and Ca2+ elevation. The number of factors involved (both
      AMPK and Ca2+, or Ca2+ only) in exercise-induced PGC-1alpha expression may differ
      among muscles.

PMID- 14570702
TI  - Identification of a novel mitochondrial protein ("mitoNEET") cross-linked
      specifically by a thiazolidinedione photoprobe.
AB  - Thiazolidinediones address underlying causes of type 2 diabetes, although their
      mechanism of action is not clearly understood. The compounds are thought to
      function as direct activators of the nuclear receptor PPARgamma (peroxisome
      proliferator-activated receptor-gamma), although pioglitazone, the weaker agonist
      of the two thiazolidinediones now in clinical use, seems to have more useful
      effects on circulating lipids. We have used tritiated pioglitazone and a
      photoaffinity cross-linker to identify a novel binding site in mitochondria. A
      saturable binding site for [3H]pioglitazone was solubilized from the membranes
      with CHAPS and migrated as a large complex by size exclusion chromatography. The
      binding correlated with a <17-kDa protein (m17), marked by a photoaffinity cross
      linker, in both subcellular location and selectivity of competition by analogs.
      The protein was isolated and identified by mass spectrometry analysis and NH2
      terminal sequencing. Three synthetic peptides with potential antigenic properties
      were synthesized from the predicted nontransmembrane sequence to generate
      antibodies in rabbits. Western blots show that this protein, which we have termed
      "mitoNEET," is located in the mitochondrial fraction of rodent brain, liver, and
      skeletal muscle, showing the identical subcellular location and migration on SDS
      PAGE as the protein cross-linked specifically by the thiazolidinedione
      photoprobe. The protein exists in low levels in preadipocytes, and expression
      increases exponentially in differentiated adipocytes. The synthetic protein bound
      to solid phase associated with a complex of solubilized mitochondrial proteins,
      including the trifunctional beta-oxidation protein. It is possible that
      thiazolidinedione modification of the function of the mitochondrial target may
      contribute to lipid lowering and/or antidiabetic actions.

PMID- 14570703
TI  - Molecular basis of the functional podocin-nephrin complex: mutations in the NPHS2
      gene disrupt nephrin targeting to lipid raft microdomains.
AB  - Hereditary nephrotic syndrome is a heterogeneous disease, characterized by heavy
      proteinuria and renal failure. Mutations of NPHS1 or NPHS2, the genes encoding
      for nephrin and podocin, lead to early onset of heavy proteinuria, and rapid
      progression to end-stage renal disease, suggesting that both proteins are
      essential for the integrity of the glomerular filter. Podocin is a stomatin
      protein family member with a predicted hairpin-like structure localizing to the
      insertion site of the slit diaphragm of podocytes, the visceral glomerular
      epithelial cells of the kidney. Here we investigate the pathomechanisms of
      different disease-causing podocin mutations. We show that wild-type podocin is
      targeted to the plasma membrane, and forms homo-oligomers involving the carboxy
      and amino terminal cytoplasmic domains. The association of podocin with
      specialized lipid raft microdomains of the plasma membrane was a prerequisite for
      recruitment of nephrin into rafts. In contrast, disease-causing mutations of
      podocin (R138Q and R138X) failed to recruit nephrin into rafts either because
      these mutants were retained in the endoplasmic reticulum (R138Q), or because they
      failed to associate with rafts (R138X) despite their presence in the plasma
      membrane. None of the mutants did augment nephrin signaling, suggesting that
      lipid raft targeting facilitates nephrin signaling. Our findings demonstrate that
      the failure of mutant podocin to recruit nephrin into lipid rafts may be
      essential for the pathogenesis of NPHS2.

PMID- 14570704
TI  - Impact of selection, mutation rate and genetic drift on human genetic variation.
AB  - The accumulation of genome-wide information on single nucleotide polymorphisms in
      humans provides an unprecedented opportunity to detect the evolutionary forces
      responsible for heterogeneity of the level of genetic variability across loci.
      Previous studies have shown that history of recombination events has produced
      long haplotype blocks in the human genome, which contribute to this
      heterogeneity. Other factors, however, such as natural selection or the
      heterogeneity of mutation rates across loci, may also lead to heterogeneity of
      genetic variability. We compared synonymous and non-synonymous variability within
      human genes with their divergence from murine orthologs. We separately analyzed
      the non-synonymous variants predicted to damage protein structure or function and
      the variants predicted to be functionally benign. The predictions were based on
      comparative sequence analysis and, in some cases, on the analysis of protein
      structure. A strong correlation between non-synonymous, benign variability and
      non-synonymous human-mouse divergence suggests that selection played an important
      role in shaping the pattern of variability in coding regions of human genes.
      However, the lack of correlation between deleterious variability and evolutionary
      divergence shows that a substantial proportion of the observed non-synonymous
      single-nucleotide polymorphisms reduces fitness and never reaches fixation.
      Evolutionary and medical implications of the impact of selection on human
      polymorphisms are discussed.

PMID- 14570705
TI  - PCDH15 is expressed in the neurosensory epithelium of the eye and ear and mutant
      alleles are responsible for both USH1F and DFNB23.
AB  - Recessive splice site and nonsense mutations of PCDH15, encoding protocadherin
      15, are known to cause deafness and retinitis pigmentosa in Usher syndrome type
      1F (USH1F). Here we report that non-syndromic recessive hearing loss (DFNB23) is
      caused by missense mutations of PCDH15. This suggests a genotype-phenotype
      correlation in which hypomorphic alleles cause non-syndromic hearing loss, while
      more severe mutations of this gene result in USH1F. We localized protocadherin 15
      to inner ear hair cell stereocilia, and to retinal photoreceptors by
      immunocytochemistry. Our results further strengthen the importance of
      protocadherin 15 in the morphogenesis and cohesion of stereocilia bundles and
      retinal photoreceptor cell maintenance or function.

PMID- 14570706
TI  - Glutathione S-transferase omega-1 modifies age-at-onset of Alzheimer disease and
      Parkinson disease.
AB  - We previously reported genetic linkage of loci controlling age-at-onset in
      Alzheimer disease (AD) and Parkinson's disease (PD) to a 15 cM region on
      chromosome 10q. Given the large number of genes in this initial starting region,
      we applied the process of 'genomic convergence' to prioritize and reduce the
      number of candidate genes for further analysis. As our second convergence factor
      we performed gene expression studies on hippocampus obtained from AD patients and
      controls. Analysis revealed that four of the genes [stearoyl-CoA desaturase; NADH
      ubiquinone oxidoreductase 1 beta subcomplex 8; protease, serine 11; and
      glutathione S-transferase, omega-1 (GSTO1)] were significantly different in their
      expression between AD and controls and mapped to the 10q age-at-onset linkage
      region, the first convergence factor. Using 2814 samples from our AD dataset
      (1773 AD patients) and 1362 samples from our PD dataset (635 PD patients),
      allelic association studies for age-at-onset effects in AD and PD revealed no
      association for three of the candidates, but a significant association was found
      for GSTO1 (P=0.007) and a second transcribed member of the GST omega class, GSTO2
      (P=0.005), located next to GSTO1. The functions of GSTO1 and GSTO2 are not well
      understood, but recent data suggest that GSTO1 maybe involved in the post
      translational modification of the inflammatory cytokine interleukin-1beta. This
      is provocative given reports of the possible role of inflammation in these two
      neurodegenerative disorders.

PMID- 14570707
TI  - Abnormalities of the vitreoretinal interface caused by dysregulated Hedgehog
      signaling during retinal development.
AB  - Mutations in Patched (PTCH), encoding the Hedgehog (Hh) receptor, underlie Basal
      Cell Naevus syndrome (BCNS) and, in addition to tumor predisposition, are
      associated with a wide range of 'patterning' defects. The basis for the
      underlying patterning problems in Hh-dependent tissues in BCNS and their long
      term consequences on tissue homeostasis are, however, not known. Hh signaling is
      required for normal growth and organization of the mammalian retina and we show
      that PtchlacZ+/- mice exhibit vitreoretinal abnormalities resembling those found
      in BCNS patients. The retinas of PtchlacZ+/- mice exhibit abnormal cell cycle
      regulation, which culminates in photoreceptor dysplasia and Muller cell-derived
      gliosis. In BCNS, the intraretinal glial response results in epiretinal membrane
      (ERM) formation, a proliferative and contractile response on the retinal surface.
      ERMs are a cause of significant visual loss in the general, especially elderly,
      population. We hypothesize that alteration of Muller cell Hh signaling may play a
      role in the pathogenesis of such age-related 'idiopathic' ERMs.

PMID- 14570708
TI  - Hnf6 and Tcf2 (MODY5) are linked in a gene network operating in a precursor cell
      domain of the embryonic pancreas.
AB  - During pancreatic organogenesis endocrine cells arise from non self-renewing
      progenitors that express Ngn3. The precursors that give rise to Ngn3+ cells are
      presumably located within duct-like structures. However, the nature of such
      precursors is poorly understood. We show that, at E13-E18, the embryonic stage
      during which the major burst of beta-cell neogenesis takes place, pancreatic duct
      cells express Hnf1beta, the product of the maturity-onset diabetes of the young
      type 5 (MODY5) gene. Ngn3+ cells at this stage invariably cluster with
      mitotically competent Hnf1beta+ cells, and are often intercalated with these
      cells in the epithelium that lines the lumen of primitive ducts. We present
      several observations that collectively indicate that Hnf1beta+ cells are the
      immediate precursors of Ngn3+ cells. We furthermore show that Hnf1beta expression
      is markedly reduced in early pancreatic epithelial cells of Hnf6-deficient mice,
      in which formation of Ngn3+ cells is defective. These findings define a precursor
      cellular stage of the embryonic pancreas and place Hnf1beta in a genetic
      hierarchy that regulates the generation of pancreatic endocrine cells.

PMID- 14570710
TI  - Dramatic tissue-specific mutation length increases are an early molecular event
      in Huntington disease pathogenesis.
AB  - Huntington disease is caused by the expansion of a CAG repeat encoding an
      extended glutamine tract in a protein called huntingtin. Although the mutant
      protein is widely expressed, the earliest and most striking neuropathological
      changes are observed in the striatum. Here we show dramatic mutation length
      increases (gains of up to 1000 CAG repeats) in human striatal cells early in the
      disease course, most likely before the onset of pathological cell loss. Studies
      of knock-in HD mouse models indicate that the size of the initial CAG repeat
      mutation may influence both onset and tissue-specific patterns of age-dependent,
      expansion-biased mutation length variability. Given that CAG repeat length
      strongly correlates with clinical severity, we suggest that somatic increases of
      mutation length may play a major role in the progressive nature and cell
      selective aspects of both adult-onset and juvenile-onset HD pathogenesis and we
      discuss the implications of this interpretation of the data presented.

PMID- 14570709
TI  - Allelism of MCKD, FJHN and GCKD caused by impairment of uromodulin export
      dynamics.
AB  - The disease complex medullary cystic disease/familial juvenile hyperuricemic
      nephropathy (MCKD/FJHN) is characterized by alteration of urinary concentrating
      ability, frequent hyperuricemia, tubulo-interstitial fibrosis, cysts at the
      cortico-medullary junction and renal failure. MCKD/FJHN is caused by mutations of
      the gene encoding uromodulin, the most abundant protein in urine. Here, we
      describe new missense mutations in three families with MCKD/FJHN and demonstrate
      allelism with a glomerulocystic kidney disease (GCKD) variant, showing
      association of cyst dilatation and collapse of glomeruli with some clinical
      features similar to MCKD/FJHN as hyperuricemia and impairment of urine
      concentrating ability. Furthermore, we provide the first functional
      characterization of uromodulin mutations. The four newly identified mutants were
      characterized by immunofluorescence and FACS analysis on transfected cells. These
      experiments showed that all uromodulin mutations cause a delay in protein export
      to the plasma membrane due to a longer retention time in the endoplasmic
      reticulum. Immunohistochemistry on GCKD and MCKD/FJHN kidney biopsies revealed
      dense intracellular accumulation of uromodulin in tubular epithelia of the thick
      ascending limb of Henle's loop. Electron microscopy demonstrated accumulation of
      dense fibrillar material within the endoplasmic reticulum. Consistently, patient
      urines show a severe reduction of excreted uromodulin. The maturation impairment
      is consistent with the clinical findings and suggests a pathogenetic mechanism
      leading to these kidney diseases.

PMID- 14570711
TI  - Promoter-restricted H3 Lys 4 di-methylation is an epigenetic mark for monoallelic
      expression.
AB  - Methylation of histone tails has been implicated in long-term epigenetic memory.
      Methylated H3 Lys 4 (K4) is a generally conserved mark for euchromatic,
      transcriptionally active regions, although the effect of this modification is
      likely also to depend on its distribution both within the euchromatic region and
      more specifically within a given gene. Here we describe a profile of H3K4 di
      methylation that is specific for monoallelically expressed genes. Both X-linked
      genes subject to X-inactivation and autosomal imprinted genes have di-methylated
      H3K4 restricted to their promoter regions. In contrast, high levels of H3K4 di
      methylation are found in both promoters and exonic parts of autosomal genes and
      of X-linked genes that escape X-inactivation. We suggest that this pattern of
      promoter restricted H3 Lys 4 di-methylation, already present in totipotent cells,
      is causally related to the long-term programming of allelic expression and
      provides an epigenetic mark for monoallelically expressed genes.

PMID- 14570712
TI  - Phosphorylation influences the translation state of FMRP-associated
      polyribosomes.
AB  - Fragile X mental retardation protein, FMRP, is absent in patients with fragile X
      syndrome, a common form of mental retardation. FMRP is a nucleocytoplasmic RNA
      binding protein that is primarily associated with polyribosomes. FMRP is believed
      to be a translational repressor and may regulate the translation of certain mRNAs
      at the base of dendritic spines in neurons. However, little is known about the
      regulation of FMRP. Using mass spectrometry and site-directed mutagenesis, we
      show that FMRP is phosphorylated between residues 483 and 521, N-terminal to the
      RGG box, both in murine brain and in cultured cells. Primary phosphorylation
      occurs on the highly conserved serine 499, which triggers hierarchical
      phosphorylation of nearby serines. FMRP is phosphorylated within 2-4 h of
      synthesis, however, phosphorylation has no effect on the half-life of the
      protein. In contrast to the Drosophila ortholog dFxr, the phosphorylation status
      of mammalian FMRP does not influence its association with specific mRNAs in vivo.
      However, we find unphosphorylated FMRP associated with actively translating
      polyribosomes while a fraction of phosphorylated FMRP is associated with
      apparently stalled polyribosomes. Our data suggest that the phosphorylation may
      regulate FMRP and that the release of FMRP-induced translational suppression may
      involve a dephosphorylation signal.

PMID- 14570713
TI  - Reduction in frataxin causes progressive accumulation of mitochondrial damage.
AB  - Frataxin protein controls iron availability in mitochondria and reduced levels
      lead to the human disease, Friedreich's ataxia (FRDA). The molecular aspects of
      disease progression are not well understood. We developed a highly regulatable
      promoter system for expressing frataxin in yeast to address the consequences of
      chronically reduced amounts of this protein. Shutting off the promoter resulted
      in changes normally associated with loss of frataxin including iron accumulation
      within the mitochondria and the induction of mitochondrial petite mutants. While
      there was considerable oxidative damage to mitochondrial proteins, the petites
      were likely due to accumulation of mitochondrial DNA lesions and subsequent DNA
      loss. Chronically reduced frataxin levels resulted in similar response patterns.
      Furthermore, nuclear DNA damage was detected in a rad52 mutant, deficient in
      double-strand break repair. We conclude that reduced frataxin levels, which is
      more representative of the disease state, results in considerable oxidative
      damage in both mitochondrial and nuclear DNA.

PMID- 14570714
TI  - Analysis of the ARMD1 locus: evidence that a mutation in HEMICENTIN-1 is
      associated with age-related macular degeneration in a large family.
AB  - Age-related macular degeneration (AMD) is a common cause of severe vision loss.
      Identification of the genes involved in AMD will lead to a better understanding
      of this disease at the molecular level, which will eventually lead to early
      detection, prevention and treatment. Previously, we mapped the ARMD1 gene to 1q25
      31 in a large family with AMD. Here, we narrow the ARMD1 locus to 14.9 Mb between
      LAMB2 and D1S3469, a region containing 50 known genes. Twenty candidate genes
      within this region were screened for mutations. Only one DNA variation, an
      A16,263G transition in exon 104 of HEMICENTIN-1, was found to segregate
      exclusively with the disease haplotype in members of this large family with AMD.
      This variation produces a non-conservative substitution of arginine for glutamine
      at amino acid position 5345 (Gln5345Arg). It was also identified in 11 other
      individuals, all of whom share a haplotype, which envelops HEMICENTIN-1, with the
      large AMD family. The affected status of all but one of those individuals
      conforms to the age-dependent penetrance observed in AMD. The amino acid at
      position 5345 of HEMICENTIN-1 was conserved as glutamine in eight species
      analyzed. RT-PCR analysis demonstrated that exon 104 of HEMICENTIN-1 is
      alternatively spliced in various cell types. Exclusive segregation of Gln5345Arg
      with the disease haplotype in this large family, amino acid conservation of
      glutamine at this position among mammals, the non-conservative nature of the
      substitution and similarities to EFEMP1 support the conclusion that HEMICENTIN-1
      is the ARMD1 gene.

PMID- 14570715
TI  - Classifying the estrogen receptor status of breast cancers by expression profiles
      reveals a poor prognosis subpopulation exhibiting high expression of the ERBB2
      receptor.
AB  - Recent work using expression profiling to computationally predict the estrogen
      receptor (ER) status of breast tumors has revealed that certain tumors are
      characterized by a high prediction uncertainty ('low-confidence'). We analyzed
      these 'low-confidence' tumors and determined that their 'uncertain' prediction
      status arises as a result of widespread perturbations in multiple genes whose
      expression is important for ER subtype discrimination. Patients with 'low
      confidence' ER+ tumors exhibited a significantly worse overall survival (P=0.03)
      and shorter time to distant metastasis (P=0.004) compared with their 'high
      confidence' ER+ counterparts, indicating that the 'high-' and 'low-confidence'
      binary distinction is clinically meaningful. We then discovered that elevated
      expression of the ERBB2 receptor is significantly correlated with a breast tumor
      exhibiting a 'low-confidence' prediction, and this association was subsequently
      validated across multiple independently derived breast cancer expression datasets
      employing a variety of different array technologies and patient populations.
      Although ERBB2 signaling has been proposed to inhibit the transcriptional
      activity of ER, a large proportion of the perturbed genes in the 'low
      confidence'/ERBB2+ samples are not known to be estrogen responsive, and a
      recently described bioinformatic algorithm (DEREF) was used to demonstrate the
      absence of potential estrogen-response elements (EREs) in their promoters. We
      propose that a significant portion of ERBB2's effects on ER+ breast tumors may
      involve ER-independent mechanisms of gene activation, which may contribute to the
      clinically aggressive behavior of the 'low-confidence' breast tumor subtype.

PMID- 14570716
TI  - Autophagy regulates the processing of amino terminal huntingtin fragments.
AB  - The N-terminus of mutant huntingtin (htt) has a polyglutamine expansion and forms
      neuronal aggregates in the brain of Huntington's disease (HD) patients. Htt
      expression in vitro activates autophagy, but it is unclear whether
      autophagic/lysosomal pathways process htt, especially N-terminal htt fragments.
      We explored the role of autophagy in htt processing in three cell lines, clonal
      striatal cells, PC12 cells and rodent embryonic cells lacking cathepsin D.
      Blocking autophagy raised levels of exogenously expressed htt1-287 or 1-969,
      reduced cell viability and increased the number of cells bearing mutant htt
      aggregates. Stimulating autophagy promoted htt degradation, including breakdown
      of caspase cleaved N-terminal htt fragments. Htt expression increased levels of
      the lysosomal enzyme cathepsin D by an autophagy-dependent pathway. Cells without
      cathepsin D accumulated more N-terminal htt fragments and cells with cathepsin D
      were more efficient in degrading wt htt than mutant htt in vitro. These results
      suggest that autophagy plays a critical role in the degradation of N-terminal
      htt. Altered processing of mutant htt by autophagy and cathepsin D may contribute
      to HD pathogenesis.

PMID- 14570717
TI  - NOD2/CARD15 and the Paneth cell: another piece in the genetic jigsaw of
      inflammatory bowel disease.

PMID- 14570718
TI  - Aspirin: still learning about the wonder drug.

PMID- 14570719
TI  - Gastrointestinal safety of AZD3582, a cyclooxygenase inhibiting nitric oxide
      donator: proof of concept study in humans.
AB  - BACKGROUND: Cyclooxygenase inhibiting nitric oxide donators (CINODs) are a new
      class of anti-inflammatory and analgesic drugs that may minimise gastrointestinal
      toxicity compared with standard non-steroidal anti-inflammatory drugs (NSAIDs) by
      virtue of nitric oxide donation. METHODS: A proof of concept study of the
      gastrointestinal safety of AZD3582, the first CINOD available for human testing,
      was conducted. Thirty one subjects were randomised to receive placebo, naproxen
      500 mg twice daily, or its nitroxybutyl derivative AZD3582 in an equimolar dose
      (750 mg twice daily) for 12 days in a double blind three period crossover
      volunteer study. At the start and end of each dosing period, gastroduodenal
      injury was assessed by endoscopy and small bowel permeability by differential
      urinary excretion of lactulose and L-rhamnose. Pharmacokinetic profiles were
      assessed at steady state. RESULTS: On naproxen, the mean total number of
      gastroduodenal erosions was 11.5 (and one subject developed an acute ulcer)
      versus 4.1 on AZD3582 (p<0.0001). More than half of the subjects had no erosions
      on AZD3582. Differences were seen for both the stomach and duodenum. Naproxen
      increased intestinal permeability (lactulose:L-rhamnose ratio 0.030 before v
      0.040 after treatment) whereas AZD3582 (0.029 before, 0.029 after; p=0.006 v
      naproxen) and placebo (0.030 before, 0.028 after; p<0.001 v naproxen) did not.
      The steady state bioavailability of naproxen metabolised from AZD3582 was 95%
      (95% confidence interval 87-101%) of that after naproxen administration.
      CONCLUSIONS: This human study supports animal data showing reduced
      gastrointestinal toxicity with the CINOD AZD3582. The potential combination of
      effective pain relief and gastrointestinal protection offered by AZD3582 warrants
      further evaluation in human clinical studies.

PMID- 14570720
TI  - Effect of Helicobacter pylori eradication on development of dyspeptic and reflux
      disease in healthy asymptomatic subjects.
AB  - BACKGROUND AND AIM: There are few data on the course of Helicobacter pylori
      infection in asymptomatic subjects. The aim of this study was to assess the
      effect of eradication therapy on the development of dyspeptic and gastro
      oesophageal reflux disease in a cohort of asymptomatic individuals observed over
      a prolonged period. METHODS: A total of 169 blood donors infected with H pylori
      who had volunteered for studies on eradication in 1990 formed the cohort. To be
      included in this cohort subjects had to have no symptoms, as determined by a
      validated symptom questionnaire at the baseline visit. Eighty eight subjects were
      infected with H pylori while 81 had successfully undergone eradication therapy.
      Subjects were followed up (annually) using the same symptom questionnaire and in
      2000 they underwent repeat endoscopy. RESULTS: Thirteen subjects developed
      symptoms during follow up. The incidence of symptoms in H pylori positive
      subjects was 1.893/100 person-years of follow up and in H pylori negative
      individuals 0.163/100 person-years of follow up. H pylori infected subjects were
      significantly more likely to develop symptoms (log rank test, p=0.003) as well as
      those infected with CagA positive strains (log rank test, p=0.017). The
      development of symptomatic gastro-oesophageal reflux disease was no different in
      individuals with and without eradication (odds ratio 0.57 (95% confidence
      interval 0.26-1.24); p=0.163). CONCLUSIONS: H pylori eradication prevents the
      development of dyspeptic symptoms and peptic ulcer disease in healthy
      asymptomatic blood donors and is not associated with an increase in the incidence
      of symptomatic gastro-oesophageal reflux disease.

PMID- 14570721
TI  - Fundic accommodation assessed by SPECT scanning: comparison with the gastric
      barostat.
AB  - BACKGROUND: Recently, single photon emission computed tomography (SPECT) scanning
      was described as a non-invasive technique to assess fundic accommodation.
      However, in contrast with the barostat, no intragastric distending force is
      applied during SPECT scanning. We hypothesised that in the absence of a barostat
      balloon, SPECT scanning largely detects the volume effect of the ingested meal
      and is a rather insensitive tool to detect fundic relaxation. METHODS: After an
      overnight fast, healthy volunteers underwent a barostat study and SPECT scanning
      on two separate days to assess: (1) meal induced fundic accommodation
      (Nutridrink, 200 ml, 300 kcal); and (2) gastric relaxation to 1 mg intravenous
      glucagon. RESULTS: Fasting fundic volumes (145 (8) v 280 (32) ml; p=0.001) and
      average postprandial volume (329 (10) v 571 (53) ml; p=0.001) were significantly
      lower measured with SPECT compared with the barostat study. Meal induced fundic
      relaxation (183 (10) v 289 (46) ml; p=0.050) and the postprandial/fasting volume
      ratio (2.32 (0.10) v 2.27 (0.29); p=0.892) did not differ significantly between
      SPECT scanning and the barostat. However, no correlation could be determined
      between accommodation volumes measured by both techniques. In contrast with meal
      induced relaxation, the glucagon induced increase in fundic volume (19 (5) v 406
      (56) ml; p=0.007) and post/pre glucagon ratio (1.16 (0.03) v 3.02 (0.54);
      p=0.046) were significantly lower when measured by SPECT scanning compared with
      the barostat. CONCLUSION: SPECT scanning detects changes in postprandial volume
      but is less suitable than the gastric barostat in detecting changes in gastric
      tone. Our study therefore questions its role as a tool to detect impaired
      accommodation and warrants further validation of this technique.

PMID- 14570722
TI  - Effect of a somatostatin analogue on gastric motor and sensory functions in
      healthy humans.
AB  - BACKGROUND: Pharmacological approaches to alter satiation may have an impact on
      functional upper gastrointestinal disorders and potentially change food intake in
      obesity. AIM: Our aim was to compare the effects of two doses of octreotide and
      placebo on postprandial symptoms, gastric accommodation, and gastric emptying
      using validated non-invasive techniques. METHODS: In a randomised, parallel
      group, two dose, double blind, placebo controlled study, 39 healthy participants
      (13 per group) were randomised to 30 or 100 micro g octreotide or placebo,
      administered subcutaneously, 30 minutes before each study. Studies were performed
      on three separate days and included scintigraphic gastric emptying of solids and
      liquids, (99m)Tc SPECT imaging to measure fasting stomach volume and gastric
      accommodation following a 300 ml Ensure meal, and a standardised nutrient drink
      test to measure maximum tolerated volume and postprandial symptoms. RESULTS:
      Relative to placebo, both doses of octreotide delayed gastric emptying of solids
      (not liquids), increased fasting gastric volume, reduced the change in gastric
      volume post meal, and decreased the sensation of fullness after a satiating meal.
      CONCLUSION: The somatostatin analogue octreotide significantly alters human
      gastric functions, including inhibition of the normal reflex responses of gastric
      volume increase and emptying of the meal. These pharmacological effects suggest
      studies of the medication in disorders of satiation, including obesity and
      dyspepsia, are warranted.

PMID- 14570723
TI  - Autoantibodies of patients with coeliac disease are insufficient to block tissue
      transglutaminase activity.
AB  - BACKGROUND AND AIMS: Coeliac disease (CD) is characterised by the presence of
      autoantibodies against tissue transglutaminase (tTG), the endomysial autoantigen.
      This study was performed to determine the effect of purified autoantibodies on
      the enzymatic activity of tTG. METHODS: Total IgA and IgG class antibodies and
      purified anti-tTG autoantibodies were isolated from sera of untreated patients
      with CD and controls. The inhibitory capacity of the antibodies on tTG activity
      was checked by a fluorometric assay based on the incorporation of monodansyl
      cadaverine into casein and by tTG-catalysed cross linking of biotinylated
      cadaverine to gliadin. RESULTS: The enriched IgA and IgG fractions of five
      patients with CD and three controls resulted in no significantly different
      inhibition of enzymatic activity. In contrast, the use of affinity purified anti
      tTG autoantibodies of 12 patients with CD led to a dose dependent reduction of
      tTG activity, compared to control immunoglobulins (n=6). However, the remaining
      activity was sufficient for cross linking of cadaverine into gliadin, and
      enzymatic tTG activity was only blocked completely by high concentrations of a
      monoclonal antibody, which is directed to the active centre of tTG. CONCLUSIONS:
      Despite a partial inhibitory effect of isolated anti-tTG autoantibodies from
      patients with CD, residual enzymatic activity remains sufficiently high to cast
      doubt on their in vivo relevance.

PMID- 14570724
TI  - Elevation of IgG antibodies against tissue transglutaminase as a diagnostic tool
      for coeliac disease in selective IgA deficiency.
AB  - BACKGROUND: IgA serum autoantibodies against tissue transglutaminase (tTG) have
      an established diagnostic value in coeliac disease, and high efficacy tests are
      widely available for their detection. However, serological evaluation of IgA
      deficient subjects is still difficult. AIMS: To evaluate the diagnostic potential
      of IgG class anti-tTG autoantibodies measured quantitatively using an enzyme
      linked immunosorbent assay (ELISA) compared with immunofluorescent detection of
      coeliac autoantibodies. PATIENTS: We tested serum samples from 325 IgA deficient
      subjects, including 78 patients with coeliac disease, 73 disease controls, and
      174 blood donors. METHODS: IgG antibodies against human recombinant tTG were
      measured with an ELISA. IgG antiendomysium antibodies (EMA) were assayed by
      indirect immunofluorescence on human jejunum and appendix sections. RESULTS: The
      IgG anti-tTG ELISA had a sensitivity of 98.7% and a specificity of 98.6%, and the
      correlation with IgG EMA titres was high (r(s)=0.91). One coeliac patient,
      initially negative in all autoantibody tests, displayed both IgG anti-tTG
      antibodies and IgG EMA during later gluten exposure. IgG anti-tTG antibodies and
      EMA titres showed significant decreases (p<0.001) in treated patients. The
      frequency of IgG anti-tTG autoantibody positivity was 9.8% among IgA deficient
      blood donors and 11 of the 12 positive subjects with known HLA-DQ haplotypes
      carried DQ2 or DQ8 alleles. CONCLUSIONS: IgG anti-tTG and IgG EMA autoantibody
      tests are highly efficient in detecting coeliac disease in IgA deficient
      patients. The high prevalence of coeliac antibodies among symptom free IgA
      deficient blood donors who also carry coeliac-type HLA-DQ genes indicates that
      all IgA deficient persons should be evaluated for coeliac disease.

PMID- 14570725
TI  - Dietary fructo-oligosaccharides and lactulose inhibit intestinal colonisation but
      stimulate translocation of salmonella in rats.
AB  - BACKGROUND AND AIMS: It is frequently assumed that dietary non-digestible
      carbohydrates improve host resistance to intestinal infections by stimulating the
      protective gut microflora. However, compelling scientific evidence from in vivo
      infection studies is lacking. Therefore, we studied the effect of several non
      digestible carbohydrates on the resistance of rats to Salmonella enteritidis
      infection. METHODS: Rats (n=8 per group) were fed "humanised" purified diets
      containing 4% lactulose, fructo-oligosaccharides (FOS), resistant starch, wheat
      fibre, or cellulose. After an adaptation period of 2 weeks the animals were
      orally infected with S enteritidis. Supplement induced changes in faecal
      biochemical and microbiological parameters were studied before infection.
      Colonisation of salmonella was determined by studying the faecal excretion of
      this pathogen and translocation by analysis of urinary nitric oxide metabolites
      over time and classical organ cultures. Intestinal mucosal myeloperoxidase
      activity was determined to quantify intestinal inflammation after infection.
      RESULTS: Despite stimulation of intestinal lactobacilli and bifidobacteria and
      inhibition of salmonella colonisation, FOS and lactulose significantly enhanced
      translocation of this pathogen. These supplements also increased cytotoxicity of
      faecal water and faecal mucin excretion, which may reflect mucosal irritation. In
      addition, caecal and colonic, but not ileal, mucosal myeloperoxidase activity was
      increased in infected rats fed FOS and lactulose. In contrast, cellulose, wheat
      fibre, and resistant starch did not affect the resistance to salmonella.
      CONCLUSIONS: In contrast to most expectations, FOS and lactulose impair the
      resistance of rats to intestinal salmonella infection. Obviously, stimulation of
      the endogenous lactobacilli and bifidobacteria is no guarantee of improved host
      defence against intestinal infections.

PMID- 14570726
TI  - Maternal milk regulation of cell infiltration and interleukin 18 in the intestine
      of suckling rat pups.
AB  - BACKGROUND: and aims: In neonates the gastrointestinal tract is exposed to food
      and bacterial antigens at a time when the gut mucosal immune system has not
      developed the ability to induce oral tolerance. This increases the risk for an
      inappropriate immune response to oral antigens. Transforming growth factor beta
      (TGF-beta) is an immunoregulatory cytokine present in high concentration in
      maternal milk. Interleukin 18 (IL-18) is a cytokine that mediates early immune
      events, and drives T cell development. We assessed the role of TGF-beta in
      mediating mucosal immune development and specifically the effect on endogenous IL
      18. METHODS: Rat pups were randomly assigned to the following groups, naturally
      suckled, maternal milk via cannula, and formula fed with and without
      physiological levels of TGF-beta2. A comparison of the immune response profile
      was then carried out. Cytokine profiles, dendritic cell, intestinal mast cell,
      and eosinophil numbers were assessed. RESULTS: We show that feeding formula
      deficient in TGF-beta2 resulted in accumulated IL-18 protein release from
      intestinal epithelial cells and IL-18 mRNA up regulation. A proinflammatory
      cytokine profile resulted in the gut, along with increased numbers of activated
      dendritic cells, eosinophils, and mast cells. Supplementation of the formula with
      TGF-beta2 down regulated the proinflammatory cytokine mRNA as well as the number
      of activated lymphocytes, eosinophils, mast cells, CD80, and CD86 positive
      dendritic cells. CONCLUSION: The data suggests an important role for maternal
      milk, in regulating immune responses after exposure to food antigens, which might
      otherwise induce deleterious immune responses in the intestine of suckling
      neonates. This regulation is potentially mediated by milk TGF-beta2, as well as
      endogenous IL-18.

PMID- 14570727
TI  - Incidence and prevalence of ulcerative colitis in Punjab, North India.
AB  - INTRODUCTION: Ulcerative colitis occurs worldwide. It is considered common in
      most of Europe and North America and uncommon in most of the developing Asian
      countries. The incidence/prevalence of ulcerative colitis varies not only
      according to geographical region but also with race and ethnicity. There are no
      reported data from India on the incidence of the disease and its prevalence.
      MATERIAL AND METHODS: A house to house survey was conducted by questionnaire,
      formulated to enquire about symptoms that are suggestive of ulcerative colitis.
      Those with prolonged diarrhoea with or without rectal bleeding were considered as
      suspected cases. These suspected cases were subjected to video
      sigmoidoscopy/colonoscopy and rectal biopsy. In addition, patients already
      diagnosed and receiving treatment for ulcerative colitis, encountered during the
      survey, were reviewed. Resurvey of the same areas was conducted after a one year
      interval to detect new cases. Using direct methods, standardised rates were
      calculated using world standard population weights 22, 18, 16, 12, 12, 9, 7, 3,
      and 1 for each 10 year age group. Standardised rates were also obtained
      separately for males, females, and combined populations, using the Punjab state
      1991 population census data. Rates were also estimated according to UK 2000
      population data. Ninety five per cent confidence intervals (95% CI) of prevalence
      and incidence rates of ulcerative colitis were estimated under the assumption
      that the distribution of cases followed a Poisson probability model. RESULTS: A
      total population of 51 910 were screened from January to March 1999. We
      identified 147 suspected cases and of these 23 were finally established as
      ulcerative colitis cases, giving a crude prevalence rate of 44.3 per 100 000
      inhabitants (95% CI 29.4-66.6). A second visit to the same areas after one year
      identified 10 suspected cases in a population of 49 834. Of these, three were
      confirmed as "definite" ulcerative colitis giving a crude incidence rate of 6.02
      cases per 100 000 inhabitants (95% CI 1.2-17.6). CONCLUSIONS: This is the first
      population based study from India reporting on the incidence and prevalence of
      ulcerative colitis. The disease frequency is not much less than that reported
      from Europe and North America.

PMID- 14570728
TI  - Expression of NOD2 in Paneth cells: a possible link to Crohn's ileitis.
AB  - BACKGROUND AND AIMS: Genetic variation in NOD2 has been associated with
      susceptibility to Crohn's disease (CD) and specifically with ileal involvement.
      The reason for the unique association of NOD2 mutations with ileal disease is
      unclear. To identify a possible link, we tested expression of NOD2 in intestinal
      tissue of CD patients and controls. PATIENTS AND METHODS: Fifty five specimens of
      ileum or colon from 21 CD patients, seven ulcerative colitis (UC) patients, and
      five controls with pathology other than CD or UC were stained for NOD2 using an
      immunoperoxidase method. RESULTS: Using a monoclonal antibody against NOD2
      developed in our laboratory, we detected uniform expression of NOD2 in terminal
      ileum Paneth cells from controls and patients as well as in metaplastic Paneth
      cells in the colon. Mechanical purification showed enriched expression of NOD2
      mRNA in ileal crypts. In Paneth cells, NOD2 was located in the cytosol in close
      proximity to the granules that contain antimicrobial peptides. We detected
      minimal NOD2 in the villous epithelium of the ileum or in the colonic epithelium
      from both CD patients and controls. CONCLUSIONS: These results suggest a role for
      NOD2 in the regulation of Paneth cell mediated responses against intestinal
      bacteria and a plausible mechanism to explain the selective association of NOD2
      mutations with ileal disease. The impaired capacity of CD associated mutations to
      sense luminal bacteria may result in increased susceptibility to certain gut
      microbes.

PMID- 14570729
TI  - Suppressive effect of aspirin on aberrant crypt foci in patients with colorectal
      cancer.
AB  - BACKGROUND: and aims: Aspirin and other non-steroidal anti-inflammatory drugs
      have been shown to reduce the risk of colorectal cancer (CRC). Animal models have
      shown that aspirin is also effective in reducing the density of aberrant crypt
      foci (ACF). The aim of the study was to evaluate the effect of chronic
      administration of aspirin on the distribution pattern and histological
      characteristics of ACF in patients with CRC. METHODS: Our study compared the
      distribution patterns and histomorphological characteristics of ACF between a
      group of CRC patients treated with low dose aspirin (n=59) and a control group
      without aspirin (n=135). ACF were visualised on methylene blue stained
      macroscopically normal mucosa, microdissected, and serially cut. RESULTS: ACF
      were found in 75.8% of mucosal samples from the control group and in 36% of
      mucosal samples from the aspirin treated group, indicating a 47% decline in
      prevalence of ACF in colonic samples of patients treated with aspirin. A
      significant reduction from 92.5% to 40% (p<0.0001) was found in distal large
      bowel samples containing one or more ACF. Similarly, the aspirin treated group
      showed a reduction in ACF density of 64% and 82%, respectively, in both proximal
      and distal parts of the colon, indicating a significant reduction in ACF/cm(2) in
      distal colon samples (p<0.01). The aspirin treated group displayed a 52%
      reduction in dysplastic ACF although this difference was not statistically
      significant. CONCLUSIONS: Our study has provided evidence of the effective
      chemopreventive action of low dose aspirin on ACF in humans.

PMID- 14570730
TI  - In vivo imaging of cellular proliferation in colorectal cancer using positron
      emission tomography.
AB  - BACKGROUND: and aims: Positron emission tomography (PET) using (18)F labelled 2
      fluoro-2-deoxy-D-glucose ((18)FDG) is an established imaging tool, although the
      recent development of a biologically stable thymidine analogue [18F] 3'-deoxy-3
      fluorothymidine ((18)FLT) has allowed PET to image cellular proliferation by
      utilising the salvage pathway of DNA synthesis. In this study, we have compared
      uptake of (18)FLT and (18)FDG with MIB-1 immunohistochemistry to evaluate the
      role of PET in quantifying in vivo cellular proliferation in colorectal cancer
      (CRC). PATIENTS AND METHODS: Patients with resectable, primary, or recurrent CRC
      were prospectively studied. Thirteen lesions from 10 patients (five males, five
      females), median age 68 years (range 54-87), were evaluated. Patients underwent
      (18)FDG and (18)FLT PET scanning. Tracer uptake within lesions was quantified
      using standardised uptake values (SUVs). Histopathological examination and MIB-1
      immunohistochemistry were performed on all lesions, and proliferation quantified
      by calculating a labelling index (% of MIB-1 positively stained nuclei within
      1500 tumour cells). RESULTS: Histology confirmed adenocarcinoma in 12 of 13
      lesions; the remaining lesion was reactive. All eight extrahepatic lesions were
      visualised using both (18)FLT and (18)FDG. Three of the five resected liver
      metastases were also avid for (18)FLT and showed high proliferation, while the
      remaining two lesions which demonstrated no uptake of (18)FLT had correspondingly
      very low proliferation. There was a statistically significant positive
      correlation (r =0.8, p<0.01) between SUVs of the tumours visualised with (18)FLT
      and the corresponding MIB-1 labelling indices. No such correlation was
      demonstrated with (18)FDG avid lesions (r =0.4). CONCLUSIONS: (18)FLT PET
      correlates with cellular proliferation markers in both primary and metastatic
      CRC. This technique could provide a mechanism for in vivo grading of malignancy
      and early prediction of response to adjuvant chemotherapy.

PMID- 14570731
TI  - Molecular and functional studies of electrogenic Na(+) transport in the distal
      colon and rectum of young and elderly subjects.
AB  - BACKGROUND: Human distal nephron and distal colon both exhibit mineralocorticoid
      sensitive electrogenic Na(+) absorption and make significant contributions to
      Na(+) homeostasis. Na(+) resorption in the distal nephron diminishes with age but
      it is unclear whether a similar change occurs in the distal colon. AIMS: To
      evaluate the effect of age on expression of apical Na(+) channels and basolateral
      Na(+), K(+)-ATPase, and on the responsiveness of electrogenic Na(+) absorption to
      mineralocorticoid stimulation in human distal colon and rectum. MATERIALS AND
      METHODS: Mucosal biopsies were obtained from healthy sigmoid colon and proximal
      rectum in "young" (aged 20-40 years) and "old" (aged 70 years or over) patients
      during routine colonoscopy/flexible sigmoidoscopy. Na(+) channel subunits and
      Na(+), K(+)-ATPase isoforms were studied at the mRNA level by in situ
      hybridisation and northern blotting, and at the protein level by
      immunocytochemistry and western blotting. The mineralocorticoid responsiveness of
      electrogenic Na(+) absorption was evaluated in the two groups by measuring
      amiloride sensitive electrical potential difference (PD) in the proximal rectum
      before and 24 hours after oral administration of 1 mg of fludrocortisone.
      RESULTS: Na(+) channel subunit and Na(+), K(+)-ATPase isoform expression at the
      level of mRNA and protein was similar in "young" and "old" patients. Both basal
      and the fludrocortisone stimulated amiloride sensitive rectal PDs were similar in
      the two groups. CONCLUSIONS: In contrast with the distal nephron,
      mineralocorticoid sensitive electrogenic Na(+) absorption in the human distal
      colon does not diminish with age, and may be particularly important in
      maintaining Na(+) homeostasis in the elderly.

PMID- 14570733
TI  - Long term benefits of hypnotherapy for irritable bowel syndrome.
AB  - BACKGROUND AND AIMS: There is now good evidence from several sources that
      hypnotherapy can relieve the symptoms of irritable bowel syndrome in the short
      term. However, there is no long term data on its benefits and this information is
      essential before the technique can be widely recommended. This study aimed to
      answer this question. PATIENTS AND METHODS: 204 patients prospectively completed
      questionnaires scoring symptoms, quality of life, anxiety, and depression before,
      immediately after, and up to six years following hypnotherapy. All subjects also
      subjectively assessed the effects of hypnotherapy retrospectively in order to
      define their "responder status". RESULTS: 71% of patients initially responded to
      therapy. Of these, 81% maintained their improvement over time while the majority
      of the remaining 19% claimed that deterioration of symptoms had only been slight.
      With respect to symptom scores, all items at follow up were significantly
      improved on pre-hypnotherapy levels (p<0.001) and showed little change from post
      hypnotherapy values. There were no significant differences in the symptom scores
      between patients assessed at 1, 2, 3, 4, or 5+ years following treatment. Quality
      of life and anxiety or depression scores were similarly still significantly
      improved at follow up (p<0.001) but did show some deterioration. Patients also
      reported a reduction in consultation rates and medication use following the
      completion of hypnotherapy. CONCLUSION: This study demonstrates that the
      beneficial effects of hypnotherapy appear to last at least five years. Thus it is
      a viable therapeutic option for the treatment of irritable bowel syndrome.

PMID- 14570732
TI  - Cluster analysis of symptoms and health seeking behaviour differentiates
      subgroups of patients with severe irritable bowel syndrome.
AB  - BACKGROUND: Irritable bowel syndrome (IBS) is a heterogeneous condition which is
      diagnosed according to specific bowel symptom clusters. The aim of the present
      study was to identify subgroups of IBS subjects using measures of rectal
      sensitivity and psychological symptoms, in addition to bowel symptoms. Such
      groupings, which cross conventional diagnostic approaches, may provide greater
      understanding of the pathogenesis of the condition and its treatment. METHOD: A K
      means cluster analysis was used to group 107 clinic patients with IBS according
      to physiological, physical, and psychological parameters. All patients had severe
      IBS and had failed to respond to usual medical treatment. Twenty nine patients
      had diarrhoea predominant IBS, 26 constipation predominant, and 52 had an
      alternating bowel habit. RESULTS: The clusters were most clearly delineated by
      two variables: "rectal perceptual threshold (volume)" and "number of doctor
      visits". Three subgroups were formed. Group I comprised patients with low
      distension thresholds and high rates of psychiatric morbidity, doctor
      consultations, interpersonal problems, and sexual abuse. Group II also had low
      distension thresholds but low rates of childhood abuse and moderate levels of
      psychiatric disorders. Group III had high distension thresholds, constipation or
      alternating IBS, and low rates of medical consultations and sexual abuse.
      CONCLUSION: The marked differences across the three groups suggest that each may
      have a different pathogenesis and respond to different treatment approaches.
      Inclusion of psychosocial factors in the analysis enabled more clinically
      meaningful groups to be identified than those traditionally determined by bowel
      symptoms alone or rectal threshold.

PMID- 14570734
TI  - Distribution of hepatitis B viral genotypes and mutations in the core promoter
      and precore regions in acute forms of liver disease in patients from Chiba,
      Japan.
AB  - BACKGROUND: Although it has been reported that different hepatitis B virus (HBV)
      genotypes induce different clinical characteristics in patients with chronic
      liver diseases (CLD), there have been few reports that have detailed the
      distribution of HBV genotypes in acute forms of liver disease. METHODS: HBV
      genotypes were determined in 61 patients who had acute forms of liver disease (45
      had acute self limited hepatitis (AH) and 16 had fulminant hepatitis (FH)) and in
      531 patients with CLD, including 19 patients with severe acute exacerbation of
      CLD. We also analysed the enhancer II, core promoter, and precore region
      sequences for the presence of mutations. RESULTS: Expression of genotype B in
      patients with acute forms of liver disease was significantly greater than in
      those with CLD (39.3% v 11.7%, respectively; p<0.001). Furthermore, expression of
      genotype B was significantly greater in patients with FH than in those with AH
      (62.5% v 31.1%, respectively; p=0.027). The precore mutation A1896 and the core
      promoter mutation at nt 1753 and 1754 were found more frequently in FH than in
      AH, and genotype B was predominant in FH regardless of the presence of these
      mutations. CONCLUSIONS: HBV genotype B was found more frequently in patients with
      acute forms of liver disease than in patients with CLD, and more frequently in
      patients with FH than in those with AH. These results suggest that this HBV
      genotype may induce more severe liver damage than other viral genotypes, at least
      in patients from Chiba, Japan.

PMID- 14570735
TI  - Liver fibrosis is not associated with steatosis but with necroinflammation in
      French patients with chronic hepatitis C.
AB  - BACKGROUND: In chronic hepatitis C, it has been suggested that steatosis could
      accelerate progression of fibrosis. However, results of the few published studies
      are controversial. AIM: To determine the characteristics (epidemiological,
      biological, and histological) associated with steatosis and its relationship with
      liver lesions (grade of necroinflammation and stage of fibrosis) in patients with
      chronic hepatitis C. METHODS: From November 2000 to July 2001, untreated
      consecutive adults with chronic hepatitis C admitted for liver biopsy were
      included in this study. On the day of liver biopsy, a questionnaire for risk
      factors was completed prospectively, and a blood sample was obtained for
      laboratory analysis. RESULTS: Our study included 290 patients (143 men, 147
      women). Mean body mass index (BMI) was 24 (3.8) kg/m(2). Proportions of patients
      with genotypes 1 and 3 were, respectively, 48% and 18%. A total of 135 patients
      (46.6%) had steatosis. Liver steatosis, in multivariate analysis, was associated
      with hepatitis C virus genotype 3, higher grade of necroinflammation, and higher
      BMI. There was no significant association between stage of fibrosis and liver
      steatosis. In multivariate analysis, high stage of fibrosis was associated with
      male sex, age over 50 years, high BMI, and high grade of necroinflammation.
      CONCLUSION: In our population of patients with chronic hepatitis C, steatosis
      does not seem to be an important determinant of liver fibrosis. High grade of
      necroinflammation is associated with a high stage of fibrosis.

PMID- 14570736
TI  - Outcomes of interferon alpha and ribavirin treatment for chronic hepatitis C in
      patients with normal serum aminotransaminases.
AB  - INTRODUCTION: Information on treatment outcomes with interferon plus ribavirin
      combination therapy in chronic hepatitis C patients with normal alanine
      aminotransaminase (ALT) levels is limited. AIM: The aims of this study were to
      assess outcomes of treatment with interferon plus ribavirin in patients with
      normal ALT levels (normal ALT group, n=52) compared with those with elevated ALT
      levels (raised ALT group, n=53), and to document the rate at which patients with
      normal ALT levels have an apparent worsening of disease, as shown by increases in
      ALT levels. RESULTS: At the end of treatment (week 48), 31 patients (59.6%) in
      the normal ALT group and 30 patients (56.6%) in the raised ALT group had
      undetectable hepatitis C virus (HCV) RNA (p=0.75). A sustained virological
      response (SVR) was achieved in 20 patients (38.5%) in the normal ALT group and in
      21 patients (39.6%) in the raised ALT group (p=0.90). Patients were subsequently
      followed up for a median of 29.8 (interquartile range 25th-75th percentile (IQR)
      20.8-36.2) months in the normal ALT group and for a median of 26.1 (IQR 17.7
      36.3) months in the raised group (p=0.20) after week 72 of treatment. Among
      patients without SVR in the normal ALT group, only three patients (9.4%)
      developed persistently raised ALT levels following therapy. CONCLUSIONS:
      Combination therapy with interferon plus ribavirin is associated with a similar
      SVR in patients with normal ALT levels compared with those with elevated ALT
      levels. In patients with normal ALT levels, virological non-response to therapy
      results in new elevations in serum ALT levels in a small minority only.

PMID- 14570737
TI  - Oats induced villous atrophy in coeliac disease.
AB  - The current trend is to allow coeliac disease (CD) patients to introduce oats to
      their gluten free diet. We sought further data from the clinical setting with
      regards to oats consumption by coeliac patients. Several oat products were tested
      for wheat contamination using a commercial enzyme linked immunoassay (ELISA) kit,
      and six samples were examined by an ELISA using a cocktail of monoclonal
      antibodies, mass spectrometry, and western blot analysis. Nineteen adult CD
      patients on a gluten free diet were challenged with 50 g of oats per day for 12
      weeks. Serological testing and gastroduodenoscopy was performed before and after
      the challenge. Biopsies were scored histologically and levels of mRNA specific
      for interferon gamma were determined by reverse transcription-polymerase chain
      reaction analysis. Oats were well tolerated by most patients but several reported
      initial abdominal discomfort and bloating. One of the patients developed partial
      villous atrophy and a rash during the first oats challenge. She subsequently
      improved on an oats free diet but developed subtotal villous atrophy and dramatic
      dermatitis during a second challenge. Five of the patients showed positive levels
      of interferon gamma mRNA after challenge. Some concerns therefore remain with
      respect to the safety of oats for coeliacs.

PMID- 14570739
TI  - Scintigraphic assessment of SO dysfunction.

PMID- 14570740
TI  - Remarkable resemblance in the mode of transmission of HCV infection among
      haemodialysis patients and IVDAs.

PMID- 14570741
TI  - Proposal for a new histological grading system for post-treatment evaluation of
      gastric MALT lymphoma.

PMID- 14570742
TI  - Physician-technician.

PMID- 14570743
TI  - Role of gastrointestinal hormones in the proliferation of normal and neoplastic
      tissues.
AB  - Gastrointestinal (GI) hormones are chemical messengers that regulate the
      physiological functions of the intestine and pancreas, including secretion,
      motility, absorption, and digestion. In addition to these well-defined
      physiological effects, GI hormones can stimulate proliferation of the
      nonneoplastic intestinal mucosa and pancreas. Furthermore, in an analogous
      fashion to breast and prostate cancer, certain GI cancers possess receptors for
      GI hormones; growth can be altered by administration of these hormones or by
      blocking their respective receptors. The GI hormones that affect proliferation,
      either stimulatory or inhibitory, include gastrin, cholecystokinin, gastrin
      releasing peptide, neurotensin, peptide YY, glucagon-like peptide-2, and
      somatostatin. The effects of these peptides on normal and neoplastic GI tissues
      will be described. Also, future perspectives and potential therapeutic
      implications will be discussed.

PMID- 14570746
TI  - Angiogenesis in endocrine tumors.
AB  - Angiogenesis is the process of new blood vessel development from preexisting
      vasculature. Although vascular endothelium is usually quiescent in the adult,
      active angiogenesis has been shown to be an important process for new vessel
      formation, tumor growth, progression, and spread. The angiogenic phenotype
      depends on the balance of proangiogenic growth factors such as vascular
      endothelial growth factor (VEGF) and inhibitors, as well as interactions with the
      extracellular matrix, allowing for endothelial migration. Endocrine glands are
      typically vascular organs, and their blood supply is essential for normal
      function and tight control of hormone feedback loops. In addition to metabolic
      factors such as hypoxia, the process of angiogenesis is also regulated by
      hormonal changes such as increased estrogen, IGF-I, and TSH levels. By measuring
      microvascular density, differences in angiogenesis have been related to
      differences in tumor behavior, and similar techniques have been applied to both
      benign and malignant endocrine tumors with the aim of identification of tumors
      that subsequently behave in an aggressive fashion. In contrast to other tumor
      types, pituitary tumors are less vascular than normal pituitary tissue, although
      the mechanism for this observation is not known. A relationship between
      angiogenesis and tumor size, tumor invasiveness, and aggressiveness has been
      shown in some pituitary tumor types, but not in others. There are few reports on
      the role of microvascular density or angiogenic factors in adrenal tumors. The
      mechanism of the vascular tumors, which include adrenomedullary tumors, found in
      patients with Von Hippel Lindau disease has been well characterized, and clinical
      trials of antiangiogenic therapy are currently being performed in patients with
      Von Hippel Lindau disease. Thyroid tumors are more vascular than normal thyroid
      tissue, and there is a clear correlation between increased VEGF expression and
      more aggressive thyroid tumor behavior and metastasis. Although parathyroid
      tissue induces angiogenesis when autotransplanted and PTH regulates both VEGF and
      MMP expression, there are few studies of angiogenesis and angiogenic factors in
      parathyroid tumors. An understanding of the balance of angiogenesis in these
      vascular tumors and mechanisms of vascular control may assist in therapeutic
      decisions and allow appropriately targeted treatment.

PMID- 14570747
TI  - Insulin-lowering agents in the management of polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) is a medical condition that has brought multiple
      specialists together. Gynecologists, endocrinologists, cardiologists,
      pediatricians, and dermatologists are all concerned with PCOS patients and share
      research data and design clinical trials to learn more about the syndrome.
      Insulin resistance is a common feature of PCOS and is more marked in obese women,
      suggesting that PCOS and obesity have a synergistic effect on the magnitude of
      the insulin disorder. Hyperinsulinemia associated with insulin resistance has
      been causally linked to all features of the syndrome, such as hyperandrogenism,
      reproductive disorders, acne, hirsutism, and metabolic disturbances. Women with
      PCOS should be evaluated for cardiovascular risk factors, such as lipid profile
      and blood pressure. Modification of diet and lifestyle should be suggested to
      those who are obese. Several insulin-lowering agents have been tested in the
      management of PCOS. In particular, metformin is the only drug currently in
      widespread clinical use for treatment of PCOS. In a high percentage of patients,
      treatment with metformin is followed by regularization of menstrual cycle,
      reduction in hyperandrogenism and in cardiovascular risk factors, and improvement
      in response to therapies for induction of ovulation.

PMID- 14570750
TI  - The timing of normal puberty and the age limits of sexual precocity: variations
      around the world, secular trends, and changes after migration.
AB  - During the past decade, possible advancement in timing of puberty has been
      reported in the United States. In addition, early pubertal development and an
      increased incidence of sexual precocity have been noticed in children, primarily
      girls, migrating for foreign adoption in several Western European countries.
      These observations are raising the issues of current differences and secular
      trends in timing of puberty in relation to ethnic, geographical, and
      socioeconomic background. None of these factors provide an unequivocal
      explanation for the earlier onset of puberty seen in the United States. In the
      formerly deprived migrating children, refeeding and catch-up growth may prime
      maturation. However, precocious puberty is seen also in some nondeprived
      migrating children. Attention has been paid to the changing milieu after
      migration, and recently, the possible role of endocrine- disrupting chemicals
      from the environment has been considered. These observations urge further study
      of the onset of puberty as a possible sensitive and early marker of the
      interactions between environmental conditions and genetic susceptibility that can
      influence physiological and pathological processes.

PMID- 14570752
TI  - Searching for the autoimmune thyroid disease susceptibility genes: from gene
      mapping to gene function.
AB  - The autoimmune thyroid diseases (AITD) are complex diseases that are caused by an
      interaction between susceptibility genes and environmental triggers. Genetic
      susceptibility, in combination with external factors (e.g., dietary iodine), is
      believed to initiate the autoimmune response to thyroid antigens. Abundant
      epidemiological data, including family and twin studies, point to a strong
      genetic influence on the development of AITD. Various techniques have been used
      to identify the genes contributing to the etiology of AITD, including candidate
      gene analysis and whole genome screening. These studies have enabled the
      identification of several loci (genetic regions) that are linked with AITD, and
      in some of these loci putative AITD susceptibility genes have been identified.
      Some of these genes/loci are unique to Graves' disease (GD) and Hashimoto's
      thyroiditis (HT), and some are common to both diseases, indicating that there is
      a shared genetic susceptibility to GD and HT. The putative GD and HT
      susceptibility genes include both immune modifying genes (e.g., human leukocyte
      antigen, cytotoxic T lymphocyte antigen-4) and thyroid-specific genes (e.g., TSH
      receptor, thyroglobulin). Most likely these loci interact, and their interactions
      may influence disease phenotype and severity. It is hoped that in the near future
      additional AITD susceptibility genes will be identified and the mechanisms by
      which they induce AITD will be unraveled.

PMID- 14570753
TI  - The Endocrine Society and Pfizer, Inc. International Award for Excellence in
      Published Clinical Research in the Journal of Clinical Endocrinology &
      Metabolism.

PMID- 14570754
TI  - The Jun N-terminal kinase inhibitor SP600125 is a ligand and antagonist of the
      aryl hydrocarbon receptor.
AB  - Exposure of the immortalized human breast epithelial cell line MCF10A to the Jun
      N-terminal kinase (JNK) inhibitor anthra[1,9-cd]pyrazol-6(2H)-one (SP600125)
      suppressed, in a concentration-dependent manner (IC50 is approximately 2 microM),
      the induction of CYP1A1 by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).
      Cotreatment with SP600125 also suppressed the accumulation of TCDD-induced
      nuclear aryl hydrocarbon receptor (AhR)-DNA complexes, as assessed by
      electrophoretic mobility shift assays. Concentrations of SP600125 < or = 50
      microM did not transform the AhR into a DNA-binding species when added to rat
      liver cytosol. However, addition of SP600125 to cytosol just before TCDD addition
      completely suppressed AhR transformation and DNA binding (IC50 approximately 7
      microM). Sucrose gradient analyses using rat liver and murine hepatoma 1c1c7
      extracts demonstrated that SP600125 competed with TCDD for binding to the AhR.
      These results suggest that SP600125 is an AhR ligand and functions as an AhR
      antagonist at concentrations used to pharmacologically inhibit JNK.

PMID- 14570755
TI  - Evidence for the validity of cortisol 6 beta-hydroxylation clearance as a new
      index for in vivo cytochrome P450 3A phenotyping in humans.
AB  - This study uses stable isotope methodology to evaluate the validity of 6beta
      hydroxylation clearance of endogenous cortisol as a new index for in vivo CYP3A
      phenotyping in humans. Important factors contradictory to the use of a
      conventional index of urinary ratio of 6beta-hydroxycortisol to cortisol (6beta
      OHF/F) to evaluate in vivo CYP3A activity are also discussed. Stable isotopically
      labeled cortisol (3-5 mg) was orally administered to three healthy adult subjects
      to accurately determine the fractional metabolic clearance specific for the 6beta
      hydroxylation of cortisol. Plasma concentrations of labeled cortisol and urinary
      excreted amounts of labeled cortisol and 6beta-OHF were analyzed by gas
      chromatography-mass spectrometry simultaneously with their endogenous
      counterparts. There was a good correlation between endogenous and exogenous 6beta
      hydroxylation clearances in the three subjects tested (r = 0.7733, 0.9112, and
      0.9534 for 2-, 4-, and 6- to 8-h urine collection periods, respectively). This
      strongly suggests that the endogenous 6beta-hydroxylation clearance can be used
      as an appropriate index for phenotyping the in vivo CYP3A activity. Furthermore,
      observed intra- (2.1- to 4.6-fold) and interindividual variabilities (ca. 5-fold)
      in the labeled cortisol renal clearance suggest that the urinary ratio 6beta
      OHF/F, a function of 6beta-hydroxylation clearance and renal clearance of
      cortisol, does not always reflect the in vivo CYP3A activity. When a macrolide
      antibiotic, clarithromycin, was administered to a healthy volunteer in a dose of
      200 mg every 12 h for 6 days, the inhibitory effects of clarithromycin on the in
      vivo CYP3A activity were clearly seen by the 6beta-hydroxylation clearance of
      endogenous cortisol but not by the urinary ratio 6beta-OHF/F.

PMID- 14570756
TI  - The beta-D-glucoside and sodium-dependent glucose transporter 1 (SGLT1)-inhibitor
      phloridzin is transported by both SGLT1 and multidrug resistance-associated
      proteins 1/2.
AB  - Phloridzin, a glucoside of the flavonoid-like polyphenol phloretin, has long been
      known to be a specific nontransportable inhibitor of the sodium-dependent glucose
      transporter SGLT1. The objective of this study was to determine whether efflux by
      multidrug resistance-associated protein (MRP) transporters might have masked the
      absorption by SGLT1 in previous studies. Various cells used as transport models
      were incubated with phloridzin (50 microM) in the absence and presence of 50
      microM 3-[[3-[2-(7-chloroquinolin-2-yl)vinyl]phenyl]-(2
      dimethylcarbamoylethylsulfanyl)methylsulfanyl] propionic acid (MK-571), a highly
      selective MRP1/MRP2 inhibitor, and the cellular uptake of phloridzin was measured
      by high performance liquid chromatography. The uptake of phloridzin by SGLT1
      transfected Chinese hamster ovary (CHO) (G6D3) cells was 1.7-fold higher than
      that by parent CHO cells (p < 0.01). In the presence of MK-571, the uptake of
      phloridzin by CHO cells increased 3.7-fold (p < 0.001). MK-571 caused an 8.0-fold
      increase in the uptake of phloridzin by G6D3 cells (p < 0.0001). Thus, in the
      absence of MRP1 efflux, transport of phloridzin by SGLT1 was clearly
      demonstrated. Similar results were obtained for the glycosides of the flavonoids
      quercetin, genistein, and diosmetin. A significantly lower accumulation of
      phloridzin in MRP2-transfected Madin-Darby canine kidney (MDCK) cells compared
      with parent MDCK cells demonstrated that phloridzin was a substrate also for MRP2
      (p < 0.05). This conclusion was further strengthened when MK-571 increased the
      uptake by MRP2-MDCK cells as much as 3.6-fold (p < 0.01). These results
      demonstrate that phloridzin, in contrast to previous notions, is transported by
      SGLT1. In addition, they demonstrate that this and other flavonoid glycosides
      unexpectedly are efficiently effluxed by both MRP1 and MRP2.

PMID- 14570757
TI  - Disposition of tacrolimus in isolated perfused rat liver: influence of
      troleandomycin, cyclosporine, and gg918.
AB  - The disposition of tacrolimus and the influence of cyclosporine, troleandomycin,
      and GF120918 (GG918, or N-[4-[2-(1,2,3,4-tetrahydro-6,7-dimethoxy-2
      isoquinolinyl)-ethyl]-phenyl]-9,10-dihydro-5-methoxy-9-oxo-4-acridine
      carboxamine) on its hepatic disposition were examined in the isolated perfused
      rat liver. Livers from groups of rats were perfused in a recirculatory manner
      following a bolus dose of tacrolimus (100 microg), a substrate for P-glycoprotein
      (P-gp) and CYP3A, or with felodipine (200 microg), a substrate only for CYP3A.
      Perfusions of each substrate were also examined in groups of rats in the presence
      of the inhibitors: troleandomycin (20 microM, CYP3A inhibitor), GG918 (1 microM,
      P-gp inhibitor), or cyclosporine (10 microM, CYP3A and P-gp inhibitor). In all
      experiments, perfusate and bile were collected for 60 min. Tacrolimus,
      felodipine, and their primary metabolites were determined in perfusate and bile
      by liquid chromatography/tandem mass spectrometry. The area under the curve (AUC)
      from 0 to 30 min was determined. For the dual CYP3A and P-gp substrate,
      tacrolimus, AUC +/- S.D. was decreased from control (2,260 +/- 430 ng. min/ml) by
      GG918 (1,730 +/- 270 ng. min/ml, P < 0.05) and was increased by troleandomycin
      (5,200 +/- 2,470 ng. min/ml, P < 0.05) and cyclosporine (4,390 +/- 2,080 ng.
      min/ml, P < 0.05). For the exclusive CYP3A substrate, felodipine, AUC was
      unchanged from control by GG918 but increased by troleandomycin and cyclosporine.
      It is concluded that GG918 increased the hepatic exposure of tacrolimus by
      inhibiting the canalicular P-gp transport, whereas GG918 has no effect on hepatic
      disposition of felodipine. These results support our hypothesis that the hepatic
      metabolic clearance of a dual substrate will be increased by inhibiting the
      efflux transporter.

PMID- 14570758
TI  - Induction of ABCC3 (MRP3) by pregnane X receptor activators.
AB  - The pregnane X receptor (PXR) mediates the induction of various genes by
      xenobiotics, including several ATP-binding cassette transporters. PXR is also
      activated by bile acids likely to prevent their accumulation to toxic levels;
      however, the role of PXR in the regulation of MRP3, an important bile acid efflux
      transporter, has not been elucidated. The impact of PXR activators on the hepatic
      expression of MRP3 was examined in vivo and in vitro. The human hepatoma cell
      lines HuH7 and HepG2 were treated with PXR activators including clotrimazole,
      rifampicin, 17beta-hydroxy-11beta-[4-dimethylamino phenyl]-17alpha-[1
      propynyl]estra-4,9-dien-3-one (RU486), metyrapone, nifedipine, lithocholic acid,
      and 5-pregnen-3beta-ol-20-one-16alpha-carbonitrile (PCN). Levels of MRP3 mRNA, as
      determined by reverse transcription-polymerase chain reaction, were induced 1.6-
      to 8-fold in a dose-dependent manner (p < 0.05). Corresponding decreases in the
      multidrug resistance-associated protein-dependent cellular retention of 5
      carboxyfluorescein were also seen in the treated HuH7 cells. In vivo studies
      demonstrated increased PXR mRNA and induction of MRP3 mRNA in the livers of wild
      type mice treated with the PXR activator RU486. On the other hand, MRP3 induction
      was not seen in the RU486-treated PXR-null mice. These results suggest that PXR
      activation may play a role in the regulation of MRP3 expression.

PMID- 14570759
TI  - Solvent effect on cDNA-expressed human sulfotransferase (SULT) activities in
      vitro.
AB  - Sulfation is an important reaction in the biotransformation of steroid hormones,
      neurotransmitters, drugs, and other xenobiotics, yet little is known about the
      effects of organic solvents on sulfotransferase (SULT) activities in vitro.
      Initial experiments found that surprisingly low levels of solvent had dramatic
      effects on sulfotransferase activity. Consequently, we evaluated the effects of
      five commonly used solvents (methanol, ethanol, acetonitrile, dimethyl sulfoxide,
      and dimethyl formamide) on activities of cDNA-expressed sulfotransferase isozymes
      1A1 (4-nitrophenol sulfation), 1A3 (dopamine sulfation), 1E1 (ethynylestradiol
      sulfation), and 2A1 (dehydroepiandrosterone sulfation). In addition, 1
      hydroxypyrene was used as a general fluorescent probe for all four
      sulfotransferase isoforms examined. When substrates were present at their
      respective isoform-specific Km values, methanol and ethanol (0.4%, v/v) generally
      had less effect than acetonitrile, dimethyl sulfoxide, and dimethyl formamide on
      sulfotransferase activities. Acetonitrile, a commonly used solvent in cytochrome
      P450 studies, inhibited SULT1A1 activities (approximately 40%) at 0.4% (v/v), but
      activated SULT1E1-mediated 1-hydroxypyrene sulfation approximately 2.6-fold.
      Assuming a two-site kinetic model, studies revealed that solvent affected Vmax1,
      Vmax2, and the Ki value of 1-hydroxypyrene sulfation mediated by SULT1E1. In
      contrast, the Km value was not affected, suggesting that solvent may potentially
      alter binding interactions of the second substrate molecule, but not the first.
      Additional experiments with expressed SULT1A1, supplemented with control protein,
      revealed that the inhibitory effect of solvent (0.4%, v/v) was reduced to <15%
      for all solvents examined. Thus, it is recommended that ethanol is used as the
      preferred solvent vehicle and that incubations with expressed enzyme contain >12
      microg/ml total protein.

PMID- 14570760
TI  - The effect of age on sildenafil biotransformation in rat and mouse liver
      microsomes.
AB  - Sildenafil [SIL (Viagra); Pfizer, New York, NY] is a widely prescribed agent for
      erectile dysfunction in men older than 65 years. The present study evaluated
      experimental models to assess age-dependent changes in SIL biotransformation
      using hepatic microsomes from male rats and mice ranging from 6 weeks to 26
      months of age. The role of specific isoforms in the conversion of SIL to its
      primary circulating metabolite, UK-103,320 (piperazine N-desmethyl sildenafil) in
      the mouse was also investigated using immunoinhibitory antibodies. Although
      CYP2C11 largely mediated UK-103,320 formation in the rat, UK-103,320 formation
      was principally inhibited by a CYP3A antibody in the mouse. An age-related
      decrement in metabolite formation rate was observed for both species, although
      this effect was more pronounced in the old rats (reduced to 7% of young) than in
      the old mice (reduced to 51% of young). CYP2C expression was assessed by Western
      blot analysis in rat and mouse livers. Age-related differences in hepatic CYP3A
      expression in the mouse were also compared with metabolite formation rates in the
      mouse model. Decrements with age in CYP2C and -3A expression in the aging rodents
      paralleled the decrements in SIL biotransformation, suggesting that age-related
      differences in SIL metabolic rate may, in part, reflect differences in
      expression. Although the role of specific CYP enzymes and the clearance values
      for this reaction may differ among species, age-related changes in these rodent
      models are consistent with the reduced clearance of SIL observed in human
      studies.

PMID- 14570761
TI  - GYKI-47261, a new AMPA [2-amino-3-(3-hydroxymethylisoxazole-4-yl)propionic acid]
      antagonist, is a CYP2E1 inducer.
AB  - CYP2E1-inducing capacity of xenobiotics was determined in cultured hepatocytes on
      the basis of enzyme activities (chlorzoxazone 6-hydroxylation and 7
      ethoxycoumarin O-dealkylation) and protein levels. Hepatocytes in culture showed
      rapid loss of CYP2E1 enzyme during 72 h. CYP2E1 inducers (ethanol, dimethyl
      sulfoxide, acetone, isopropanol, pyrazole, and imidazole) were able to prevent
      the fast decrease of the activities and protein levels of CYP2E1 enzyme.
      Imidazole was found to be the most effective inducer in rat hepatocytes, and it
      was selected as a reference in subsequent experiments. The effect of GYKI-47261
      [6-(4-aminophenyl)-8-chloro-2-methyl-11H-imidazo[1,2c] [2,3]benzodiazepine], a
      new AMPA [2-amino-3-(3-hydroxymethylisoxazole-4-yl)propionic acid] antagonist
      drug-candidate, was also tested in the in vitro system. On the basis of enzyme
      activities and CYP2E1 protein content of rat hepatocytes, GYKI-47261 was
      considered as a potent CYP2E1 inducer. Furthermore, it was more effective than
      imidazole, since 10 microM GYKI-47261 produced the maximal induction, whereas 500
      microM imidazole brought about the maximal response. Human hepatocytes were more
      sensitive to GYKI-47261 than were rat cells. In rat hepatocytes, 10 microM caused
      maximal increase, whereas 0.01 microM produced the highest induction in human
      cells. Elevation of CYP2E1 gene transcription as the mechanism of induction
      caused by GYKI-47261 can be excluded. It seems to act mainly on stabilization of
      CYP2E1 enzyme protein, whereas the role of stabilization of CYP2E1 mRNA can be
      considered negligible. Although the imidazole part of GYKI-47261 can explain its
      CYP2E1-inducing capacity, the other part of the molecule must contribute to the
      final inducing potency.

PMID- 14570762
TI  - Induction of multidrug resistance protein 3 (mrp3) in vivo is independent of
      constitutive androstane receptor.
AB  - We previously demonstrated that multidrug resistance protein 3 (Mrp3/ABCC3) is
      induced in rat liver by phenobarbital (PB) and several other microsomal enzyme
      inducers that induce cytochrome P450 2B (CYP2B). CYP2B is induced by constitutive
      androstane receptor (CAR)-retinoid X receptor (RXR) heterodimer binding to a
      phenobarbital-responsive promoter element in the CYP2B promoter. Hepatic mRNA
      levels of CYP2B and Mrp3 were measured in three models of altered CAR activity to
      determine whether CAR is also involved in the induction of Mrp3. In Wistar Kyoto
      rats, where males express higher CAR protein levels than females, the induction
      of CYP2B1/2 was significantly higher in males than in females by PB, diallyl
      sulfide, and trans-stilbene oxide but not oltipraz. Mrp3 was induced by each of
      these treatments, but in contrast to CYP2B1/2, to a similar magnitude in males
      and females. In male hepatocyte-specific RXRalpha-/- mice, CYP2B10 was not
      induced by diallyl sulfide or oltipraz but remained inducible by PB and trans
      stilbene oxide after considering the decrease in basal CYP2B10 expression. Mrp3,
      however, was induced by PB, diallyl sulfide, trans-stilbene oxide and oltipraz in
      both wild-type and RXRalpha-/- mice. Additionally, constitutive expression of
      Mrp3 was significantly reduced in RXRalpha-/- mice. In CAR-/- mice, the robust
      induction of CYP2B10 by PB was completely absent. However, Mrp3 was equally
      induced both in wild-type and CAR-/- mice by PB. These data clearly demonstrate
      that induction of hepatic Mrp3 by PB and other microsomal enzyme inducers is CAR
      independent and implies a role for RXRalpha in the constitutive expression of
      Mrp3.

PMID- 14570763
TI  - Use of anti-(+)-methamphetamine monoclonal antibody to significantly alter (+)
      methamphetamine and (+)-amphetamine disposition in rats.
AB  - These studies examined the effects of a high-affinity anti-(+)-methamphetamine
      monoclonal antibody (mAb; KD = 11 nM) on (+)-methamphetamine [(+)-METH] and (+)
      amphetamine [(+)-AMP] serum and tissue disposition and serum protein binding
      following i.v. (+)-METH administration. Male Sprague-Dawley rats were pretreated
      with a buffer solution (control rats) or with anti-(+)-METH mAb [equimolar in
      binding sites to the (+)-METH dose]. The next day, both groups received a 1 mg/kg
      i.v. (+)-METH dose. At various time points after (+)-METH administration, rats
      were sacrificed (n = 3 per time point), and serum and tissues were collected. (+)
      METH serum protein binding was increased from approximately 5% in controls to
      approximately 88 to 99% in the mAb-treated rats. The (+)-METH area under the
      concentration versus time curves from 0 to 4.5 h (AUC0-4.5 h) in mAb-treated rats
      showed an increase of >6600% for serum and a decrease of >60% for brain, compared
      with buffer-treated controls. Differential effects of anti-METH mAb on (+)-METH
      concentrations were observed in other tissues. For example, in the liver, anti
      (+)-METH mAb caused significant increases in (+)-METH concentrations. The AUC0
      4.5 h for (+)-AMP, a pharmacologically active metabolite, was decreased by
      approximately 50% in all tissues examined. These data show that pretreatment with
      an anti-(+)-METH mAb can significantly alter the disposition of (+)-METH and (+)
      AMP in rats. Since the mAb has no significant cross-reactivity with (+)-AMP, the
      data suggest that the mAb reduced (+)-METH metabolic clearance through high
      affinity binding to (+)-METH. Finally, rapidly equilibrating tissues, like the
      brain, appear to be preferentially protected by the mAb.

PMID- 14570764
TI  - Studies on the chemical reactivity of diclofenac acyl glucuronide with
      glutathione: identification of diclofenac-S-acyl-glutathione in rat bile.
AB  - Diclofenac, a nonsteroidal anti-inflammatory drug, is metabolized to a reactive
      acyl glucuronide that has been proposed to mediate toxic adverse drug reactions
      associated with its use. In the present study, we examined the ability of
      diclofenac acyl glucuronide (D-1-O-G) to transacylate glutathione (GSH) in vitro
      in buffer and in vivo in rats. Thus, in vitro reactions of D-1-O-G (100 microM)
      with GSH (10 mM) at pH 7.4 and 37 degrees C showed a linear time-dependent
      formation of diclofenac-S-acyl-glutathione (D-SG, 3 microM/h) through 60 min of
      incubation, reaching a maximum of 3.7 microM after 2 h of incubation. The major
      reaction that occurred was acyl migration of D-1-O-G (t1/2, 54 min) to less
      reactive isomers. The D-SG thioester product was shown to be unstable by
      degrading primarily to 1-(2,6-dichlorophenyl)indolin-2-one and by hydrolysis to
      diclofenac. After administration of diclofenac to rats (200 mg/kg), bile was
      collected and analyzed for D-SG by liquid chromatography-tandem mass
      spectrometry. Results indicated the presence of D-SG, which was confirmed by
      coelution with synthetic standard and by its tandem mass spectrum. When the
      reactivity of D-SG (100 microM) was compared with D-1-O-G (100 microM) in vitro
      in reactions with N-acetylcysteine (NAC, 10 mM), results showed the quantitative
      reaction of D-SG with NAC after 30 min of incubation, whereas only approximately
      1% of D-1-O-G reacted to form diclofenac-S-acyl-NAC at the same time point.
      Results from these studies indicate that GSH reacts with D-1-O-G in vitro, and
      presumably in vivo, to form D-SG, and that the product D-SG thioester is
      chemically more reactive in transacylation-type reactions than the D-1-O-G
      metabolite.

PMID- 14570765
TI  - Constitutive expression of various xenobiotic and endobiotic transporter mRNAs in
      the choroid plexus of rats.
AB  - The aim of this study was to quantitatively determine the constitutive expression
      levels of various transporter mRNAs in rat choroid plexus. To provide a reference
      for the relative expression levels, the expression of various transporter mRNAs
      in choroid plexus were compared with that in liver, kidney, and ileum. The mRNA
      levels of multidrug resistance protein (Mrp)1, 2, 3, 4, 5, and 6; multidrug
      resistance (Mdr)1a, 1b, and 2; organic anion transporting polypeptide (Oatp)1, 2,
      3, 4, 5, 9, 12, and Oat-K (1/2); organic anion transporter (Oat)1, 2, and 3;
      organic cation transporter (Oct)1, 2, 3, N1, and N2; bile acid transporters
      sodium taurocholate cotransporting polypeptide (Ntcp), bile salt excretory
      protein (Bsep), and ileal bile acid transporter (Ibat); divalent metal
      transporter 1 (DMT1), Menke's and Wilson's metal transporters; equilibrative
      nucleotide transporters (Ent) 1 and 2, and constitutive nucleotide transporters
      (Cnt)1 and 2; peptide transporters (Pept)1 and 2; as well as ATP-binding cassette
      (Abc)G5 and 8 were measured in choroid plexus by the branched DNA signal
      amplification method. Mrp1, 4, and 5, Oatp3, Menke's transporter, DMT1, Ent1, and
      Pept2 mRNAs were expressed in choroid plexus at higher levels than in liver,
      kidney, or ileum. OctN1 and N2, Oatp2, Oat2 and 3, and Cnt1 and 2 mRNAs
      expressions were detectable in choroid plexus, but the levels were lower compared
      with that in liver, kidney, or ileum. The remaining transporters [Mrp2, Mrp3,
      Oct1, Oct2, Oatp1, Oatp4, Oatp5, Oatp12, Oat-K (1/2), Ntcp, Bsep, Ibat, Mdr1a,
      Mdr1b, Mdr2, Oat1, Ent2, Pept1, AbcG5, AbcG8] were expressed at very low levels
      in choroid plexus. The constitutive expression levels of different transporters
      in choroid plexus may provide an insight into the range of xenobiotics that can
      potentially be transported by the choroid plexus, thereby providing a means of
      xenobiotic detoxification in the brain.

PMID- 14570766
TI  - Characterization of mouse small intestinal cytochrome P450 expression.
AB  - The expression of biotransformation enzymes in mouse small intestine is poorly
      characterized, which limits the utility of transgenic or knockout mouse models
      for first-pass drug metabolism studies. In response, we have systematically
      examined the composition and inducibility of cytochrome P450 (P450) protein and
      mRNA in mouse small intestinal epithelial cells (enterocytes). RNA-PCR was
      conducted to confirm the expression and identity of CYP1A1, 1B1, 2B10, 2B19,
      2B20, 2C29, 2C38, 2C40, 2E1, 3A11, 3A13, 3A16, 3A25, and 3A44 in the enterocytes
      of untreated mice, but CYP1A2, 2A4/5, 2A12, 2C37, 2C39, and 2F2 were not
      detected. The inducibility of CYP2B, 2C, and 3A subfamily forms was determined by
      real-time quantitative RNA-PCR. All five CYP3A forms were induced, in a range
      from 1.7- to 4.5-fold, by dexamethasone (DEX). Phenobarbital (PB) induced CYP2B9,
      CYP2B10, and CYP2B20 mRNAs and suppressed CYP2B19 mRNA levels. PB also induced
      CYP2C29 and CYP2C40, but not CYP2C38 mRNA. At the protein level, CYP1A1, CYP1B1,
      CYP2B, CYP2C, CYP2E1, and CYP3A were detected in enterocytes from untreated mice
      by immunoblot analysis. CYP1A1 was inducible by beta-naphthoflavone (BNF), CYP2B
      and CYP2C by PB, and CYP3A by DEX. CYP2B, 2C, and 3A proteins were all expressed
      at high levels proximally, and decreased distally. The inducibility of CYP1A1
      followed a similar pattern. Intestinal P450 expression was compared between
      C57BL/6 (B6) and 129/sv (129) mice, strains commonly used in the preparation of
      transgenic and knockout mouse models. There was no significant strain difference
      in constitutive levels or induction patterns for CYP2B, 2C, and 3A protein.
      However, CYP1A1 was induced to a high level by BNF in B6 mice, but was not
      induced in the 129 mice.

PMID- 14570767
TI  - Mechanism-based inhibition of human liver microsomal cytochrome P450 1A2 by
      zileuton, a 5-lipoxygenase inhibitor.
AB  - Zileuton, a 5-lipoxygenase inhibitor, was evaluated as an inhibitor of cytochrome
      P450 activity in human liver microsomes. In the absence of preincubation, the
      racemate was found to be a weak inhibitor (IC50 > 100 microM) of phenacetin O
      deethylation (POD) (CYP1A2), paclitaxel 6alpha-hydroxylation (CYP2C8), diclofenac
      4'-hydroxylation (CYP2C9), (S)-mephenytoin 4'-hydroxylation (CYP2C19), bufuralol
      1'-hydroxylation (CYP2D6), testosterone 6beta-hydroxylation (CYP3A4),
      chlorzoxazone 6-hydroxylation (CYP2E1), and bupropion hydroxylation (CYP2B6).
      When preincubated with NADPH-fortified human liver microsomes in the absence of
      substrate, zileuton (racemate) was shown to inhibit POD. The effect was NADPH-,
      time-, and concentration-dependent, and was characterized by a kinact (maximal
      rate of enzyme inactivation) and apparent KI(inhibitor concentration that
      supports half the maximal rate of inactivation) of 0.035 min(-1) and 117 microM,
      respectively (kinact/KIratio of 0.0003 min-1 microM(-1)). Preincubation-dependent
      inhibition of POD activity was also observed with the individual (S)-(-)- and (R)
      (+)-enantiomers of zileuton [(S)-(-)-zileuton; kinact, 0.037 min(-1), KI, 98.2
      microM, kinact/KIratio, 0.0004 min(-1) microM(-1); (R)-(+)-zileuton; kinact,
      0.012 min(-1), KI, 66.6 microM, kinact/KIratio, 0.0002 min(-1) microM(-1)]. In
      addition, the inhibition of CYP1A2 was not reversed in the presence of reduced
      glutathione, catalase, and superoxide dismutase and was refractory to dialysis.
      Therefore, zileuton was characterized as a mechanism-based inhibitor of human
      liver microsomal CYP1A2. Mechanism-based inhibition of CYP1A2 may explain why
      zileuton decreases the oral clearance of antipyrine, propranolol, (R)-warfarin,
      and theophylline, at doses that have a minimal effect on the pharmacokinetics of
      (S)-warfarin, phenytoin, and terfenadine.

PMID- 14570768
TI  - N-glucuronidation of nicotine and cotinine by human liver microsomes and
      heterologously expressed UDP-glucuronosyltransferases.
AB  - Nicotine is considered the major addictive agent in tobacco. Tobacco users
      extensively metabolize nicotine to cotinine. Both nicotine and cotinine undergo N
      glucuronidation. Human liver microsomes have been shown to catalyze the formation
      of these N-glucuronides. However, which UDP-glucuronosyltransferases contribute
      to this catalysis has not been identified. To identify these enzymes, we
      initially measured the rates of glucuronidation by 15 human liver microsome
      samples. Fourteen of the samples glucuronidated both nicotine and cotinine at
      rates ranging from 146 to 673 pmol/min/mg protein and 140 to 908 pmol/min/mg
      protein, respectively. The rates of nicotine glucuronidation and cotinine
      glucuronidation by these 14 samples were correlated, r = 0.97 (p < 0.0001). The
      glucuronidation of nicotine and cotinine by heterologously expressed UGT1A3,
      UGT1A4, and UGT1A9 was also determined. All three enzymes catalyzed the
      glucuronidation of nicotine. However, the rate of catalysis by UGT1A4 Supersomes
      was more than 30-fold greater than that by either UGT1A3 Supersomes or UGT1A9
      Supersomes. Interestingly, when expressed per UGT1A protein, measured by a UGT1A
      specific antibody, cell lysate from V79-expressed UGT1A9 catalyzed nicotine
      glucuronidation at a rate 17-fold greater than did UGT1A9 Supersomes. UGT1A4
      Supersomes also catalyzed cotinine N-glucuronidation, but at one-tenth the rate
      of nicotine glucuronidation. Cotinine glucuronidation by either UGT1A3 or UGT1A9
      was not detected. Both propofol, a UGT1A9 substrate, and imipramine, a UGT1A4
      substrate, inhibited the glucuronidation of nicotine and cotinine by human liver
      microsomes. Taken together, these data support a role for both UGT1A9 and UGT1A4
      in the catalysis of nicotine and cotinine N-glucuronidation.

PMID- 14570769
TI  - Mechanism-based inactivation of human recombinant P450 2C9 by the nonsteroidal
      anti-inflammatory drug suprofen.
AB  - The nonsteroidal anti-inflammatory agent (+ or -)-suprofen [alpha-methyl-4-(2
      thienylcarbonyl)benzeneacetic acid] was evaluated as a P450 2C9 inactivator. (+
      or -)-Suprofen inactivated the diclofenac-4-hydroxylase activity of baculovirus
      expressed P450 2C9 in a time- and concentration-dependent manner, which was
      consistent with mechanism-based inactivation. The loss of activity followed
      pseudo-first-order kinetics and was suprofen- and NADPH-dependent. The kinetic
      parameters for inactivation kinact and KI were 0.091 min-1 and 3.7 microM,
      respectively, and the partition ratio was 101. Although P450 2C9 substrate S
      warfarin partially protected against inactivation, reactive oxygen scavengers
      such as superoxide dismutase and catalase did not prevent inactivation. Extensive
      dialysis did not regenerate enzyme activity, suggesting that inactivation
      proceeded via covalent modification. Inactivated P450 2C9 lost <10% of its
      ability to form a CO-reduced complex, suggesting that inactivation may have
      resulted from covalent modification of apoprotein. Addition of exogenous
      nucleophiles such as glutathione and semicarbazide partially protected against
      inactivation. Apart from the metabolism of suprofen to 5-hydroxysuprofen, the
      formation of a suprofen-glutathione conjugate was also discernible in microsomal
      mixtures containing glutathione. Time of flight mass spectrometry revealed a
      protonated monoisotopic mass of 566.1304 for this conjugate, consistent with an
      elemental composition of C24H28N3O9S2. The mass spectrum indicated that
      conjugation had occurred on the intact thiophene ring, presumably via a thioether
      linkage. Further evidence for the formation of an electrophilic intermediate in
      suprofen-P450 2C9 incubations was obtained via the characterization of a novel
      pyridazine adduct upon addition of semicarbazide to the microsomal mixtures. The
      pyridazine derivative had a protonated monoisotopic mass of 257.0895 that was
      consistent with an elemental composition of C14H13O3N2. The formation of the
      stable pyridazine adduct suggested the generation of an electrophilic gamma
      thioketo-alpha, beta-unsaturated aldehyde, analogous to that observed during the
      cytochrome P450-mediated bioactivation of furan. This electrophilic alpha, beta
      unsaturated aldehyde represents a possible reactive intermediate that
      bioalkylates P450 2C9.

PMID- 14570770
TI  - Transactivation of glucocorticoid-inducible rat aryl sulfotransferase (SULT1A1)
      gene transcription.
AB  - The purpose of the current study was to establish the role of the glucocorticoid
      receptor (GR) and androgen receptor (AR) transcription factors in the
      transactivation of rat aryl sulfotransferase (SULT1A1) gene transcription and to
      identify the functional hormone-responsive element(s) in the SULT1A1 gene. A cis
      acting inverted repeat with three intervening bases (IR3) was identified in the
      5'-flanking of the SULT1A1 gene that mediates the transactivation of SULT1A1 gene
      transcription by both the GR and AR. CV-1 cells were cotransfected with SULT1A1
      luciferase reporter plasmids and either wild-type or mutant GR or AR expression
      constructs. In cotransfectants expressing the wild-type GR, treatment with
      triamcinolone acetonide produced an approximately 4- to 6-fold induction of
      luciferase activity in IR3-containing SULT1A1 reporter plasmids. IR3-containing
      SULT1A1 reporter constructs were also activated by treatment with the synthetic
      androgen R1881 in cells cotransfected with wild-type but not mutant AR. In
      primary cultured rat hepatocytes, androgen-inducible expression of IR3-containing
      SULT1A1 reporter plasmids required cotransfection with AR expression plasmid.
      Targeted disruption of the SULT1A1 IR3 by mutation of a conserved GT sequence in
      the 3' half-site of the element ablated GR and AR responsiveness. These results
      indicate that a proximal IR3 element in the 5'-flanking region of the rat SULT1A1
      gene is sufficient for the transactivation of SULT1A1 gene transcription by the
      GR and AR, and that relative to the GR, functional AR activity is reduced in
      primary cultured rat hepatocytes.

PMID- 14570772
TI  - Human cytochrome p450 inhibition and metabolic-intermediate complex formation by
      goldenseal extract and its methylenedioxyphenyl components.
AB  - The concurrent use of herbal medicinals with prescription and over-the-counter
      drugs carries a risk for unanticipated adverse drug-botanical pharmacokinetic
      interactions, particularly as a result of cytochrome P450 (P450) inhibition.
      Extracts of goldenseal (Hydrastis canadensis) containing approximately equal
      concentrations ( approximately 17 mM) of two methylenedioxyphenyl alkaloids,
      berberine and hydrastine, inhibited with increasing potency (CYP2C9) diclofenac
      4'-hydroxylation, (CYP2D6) bufuralol 1'-hydroxylation, and (CYP3A4) testosterone
      6beta-hydroxylation activities in human hepatic microsomes. The inhibition of
      testosterone 6beta-hydroxylation activity was noncompetitive with an apparent Ki
      of 0.11% extract. Of the methylenedioxyphenyl alkaloids, berberine (IC50 = 45
      microM) was the more inhibitory toward bufuralol 1'-hydroxylation and hydrastine
      (IC50 approximately 350 microM for both isomers), toward diclofenac 4'
      hydroxylation. For testosterone 6beta-hydroxylation, berberine was the least
      inhibitory component (IC50 approximately 400 microM). Hydrastine inhibited
      testosterone 6beta-hydroxylation with IC50 values for the (+)- and (-)-isomers of
      25 and 30 microM, respectively. For (-)-hydrastine, an apparent Ki value of 18
      microM without preincubation and an NADPH-dependent mechanism-based inhibition
      with a kinactivation of 0.23 min(-1) and a KI of approximately 110 microM were
      determined. Cytochrome P450 metabolic-intermediate (MI) complex formation could
      be demonstrated for both hydrastine isomers. With expressed P450 isoforms,
      hydrastine formed a P450 MI complex with CYP2C9, CYP2D6, and CYP3A4. Coexpression
      of cytochrome b5 with the P450 isoforms enhanced the rate but not the extent of
      P450 MI complex formation.

PMID- 14570771
TI  - Preclinical characterization of 2-[3-[3-[(5-ethyl-4'-fluoro-2-hydroxy[1,1'
      biphenyl]-4-yl)oxy]propoxy]-2-propylphenoxy]benzoic acid metabolism: in vitro
      species comparison and in vivo disposition in rats.
AB  - Assessment of the pharmacokinetics of [14C]2-[3-[3-[(5-ethyl-4'-fluoro-2
      hydroxy[1,1'-biphenyl]-4-yl)oxy]propoxy]-2-propylphenoxy-]benzoic acid
      ([14C]LY293111), an experimental anti-cancer agent, suggested long-lived
      circulating metabolites in rats. In vivo metabolites of LY293111 were examined in
      plasma, bile, urine, and feces of Fischer 344 (F344) rats after oral
      administration of [14C]LY293111. Metabolites were profiled by high-performance
      liquid chromatography-radiochromatography, and identified by liquid
      chromatography (LC)/mass spectrometry and LC/NMR. The major in vivo metabolites
      of LY293111 identified in rats were phenolic (ether), acyl, and bisglucuronides
      of LY293111. Measurement of radioactivity in rat plasma confirmed that a fraction
      of LY293111-derived material was irreversibly bound to plasma protein and that
      this bound fraction increased over time. This was consistent with the observed
      disparity in half-lives between LY293111 and total radioactivity in rats and
      monkeys, and is likely due to covalent modification of proteins by the acyl
      glucuronide. In vitro metabolism of [14C]LY293111 in liver slices from CD-1 mice,
      F344 rats, rhesus and cynomolgus monkeys, and humans indicates that
      glucuronidation was the primary metabolic pathway in all species. The acyl
      glucuronide was the most prevalent radioactive peak (16% of total 14C) produced
      by F344 rat slices, whereas the ether glucuronide was the major metabolite in all
      other species (26-36% of total 14C). Several minor hydroxylated metabolites were
      detected in F344 rat slice extracts but were not observed in other species. The
      data presented suggest that covalent modification of proteins by LY293111 acyl
      glucuronide is possible in multiple species, although the relative reactivity of
      this metabolite appears to be low compared with those known to cause adverse drug
      reactions.

PMID- 14570773
TI  - Metabolism of rofecoxib in vitro using human liver subcellular fractions.
AB  - The metabolism of rofecoxib, a potent and selective inhibitor of cyclooxygenase
      2, was examined in vitro using human liver subcellular fractions. The
      biotransformation of rofecoxib was highly dependent on the subcellular fraction
      and the redox system used. In liver microsomal incubations, NADPH-dependent
      oxidation of rofecoxib to 5-hydroxyrofecoxib predominated, whereas NADPH
      dependent reduction of rofecoxib to the 3,4-dihydrohydroxy acid metabolites
      predominated in cytosolic incubations. In incubations with S9 fractions,
      metabolites resulting from both oxidative and reductive pathways were observed.
      In contrast to microsomes, the oxidation of rofecoxib to 5-hydroxyrofecoxib by S9
      fractions followed two pathways, one NADPH-dependent and one NAD+-dependent (non
      cytochrome P450), with the latter accounting for about 40% of total activity. The
      5-hydroxyrofecoxib thus formed was found to undergo NADPH-dependent reduction
      ("back reduction") to rofecoxib in incubations with liver cytosolic fractions. In
      incubations with dialyzed liver cytosol, net hydration of rofecoxib to form 3,4
      dihydro-5-hydroxyrofecoxib was observed, whereas the 3,4-dihydrohydroxy acid
      derivatives were formed when NADPH was present. Although 3,4-dihydro-5
      hydroxyrofecoxib could be reduced to the 3,4-dihydrohydroxy acid by cytosol in
      the presence of NADPH, the former species does not appear to serve as an
      intermediate in the overall reductive pathway of rofecoxib metabolism. In
      incubations of greater than 2 h with S9 fractions, net reductive metabolism
      predominated over oxidative metabolism. These in vitro results are consistent
      with previous findings on the metabolism of rofecoxib in vivo in human and
      provide a valuable insight into mechanistic aspects of the complex metabolism of
      this drug.

PMID- 14570774
TI  - Metabolism and disposition of novel des-fluoro quinolone garenoxacin in
      experimental animals and an interspecies scaling of pharmacokinetic parameters.
AB  - Garenoxacin is a novel quinolone that does not have a fluorine substituent at the
      C-6 position in the quinoline ring. Garenoxacin or 14C-garenoxacin was
      intravenously or orally administered to rats, dogs, and monkeys. Metabolic
      profiles and pharmacokinetic parameters were investigated focusing on the species
      differences and the allometric scaling of pharmacokinetic parameters. Garenoxacin
      was well absorbed following oral administration then underwent phase II
      metabolism in all species tested. Major metabolites of garenoxacin were the
      sulfate of garenoxacin (M1) and glucuronide (M6). Oxidative metabolites were
      present in very minor concentrations in all species tested. Another minor route
      of metabolism was the formation of the carbamoyl glucuronide. Garenoxacin is
      characterized across species by the observation that it circulates systemically,
      is excreted renally as unchanged drug, and is metabolized to M1 and M6, which are
      excreted specifically into the bile. The total clearances (CL) were 12.1, 2.43,
      and 3.39 ml/min/kg for rats, dogs, and monkeys, respectively. The distribution
      volume values of garenoxacin (Vss) were 0.88, 1.29, and 0.96 l/kg for rats, dogs,
      and monkeys, respectively. In all animals tested, the extrarenal clearance was
      larger than the renal clearance, and neither of the clearances was limited by
      blood flow. Despite these conditions, garenoxacin showed a good correlation for
      CL and Vss for allometric interspecies scaling.

PMID- 14570776
TI  - Identification of zomepirac-S-acyl-glutathione in vitro in incubations with rat
      hepatocytes and in vivo in rat bile.
AB  - Zomepirac (ZP), a nonsteroidal anti-inflammatory drug that was withdrawn from
      use, is metabolized to zomepirac-1-O-acyl-glucuronide (ZP-1-O-G), a chemically
      reactive conjugate that has been implicated in the toxicity of the drug. In the
      present studies, we investigated the ability of ZP to become bioactivated to
      reactive metabolites that transacylate glutathione (GSH) forming ZP-S-acyl
      glutathione thioester (ZP-SG) in vitro and in vivo in rat. When ZP (100 microM)
      was incubated with rat hepatocytes, ZP-SG was detected in incubation extracts by
      a sensitive selected reaction monitoring liquid chromatography/tandem mass
      spectrometry (LC/MS-MS) technique. The initial formation rate of ZP-SG was rapid
      and reached a maximum concentration of 0.24 +/- 0.03 nM after 4 min of
      incubation, then decreased, in a fairly linear fashion, to 0.07 +/- 0.03 nM after
      60 min of incubation. The product ZP-SG (1 microM) was shown to be unstable by
      undergoing rapid hydrolysis (apparent half-life approximately 0.8 min) in
      incubations with rat hepatocytes. After administration of ZP to a male Sprague
      Dawley rat (100 mg/kg i.p.), bile was collected and analyzed for ZP-SG by LC/MS
      MS. Results indicated the presence of ZP-SG in bile (6.7 microg excreted after 6
      h of collection), which was confirmed by coelution with synthetic standard and by
      its tandem mass spectrum. Together, these results demonstrate that ZP becomes
      metabolically activated in vitro in rat hepatocytes and in vivo in rat to
      reactive acylating derivative(s), such as ZP-1-O-G, that transacylate GSH forming
      ZP-SG. Finally, we propose that ZP-SG thioester could be used as a marker
      derivative for mechanistic studies on the bioactivation of the drug.

PMID- 14570775
TI  - Pharmacokinetics of a tumor necrosis factor-alpha phosphorothioate 2'-O-(2
      methoxyethyl) modified antisense oligonucleotide: comparison across species.
AB  - The pharmacokinetics of a 2'-O-(2-methoxyethyl)-ribose modified phosphorothioate
      oligonucleotide, ISIS 104838 (human tumor necrosis factor-alpha antisense), have
      been characterized in mouse, rat, dog, monkey, and human. Plasma pharmacokinetics
      after i.v. administration exhibited relatively rapid distribution from plasma to
      tissues with a distribution half-life estimated from approximately 15 to 45 min
      in all species. Absorption after s.c. injection was high (80-100%), and
      absorption after intrajejunal administration in proprietary formulations was as
      high as 10% bioavailability compared with i.v. administration. Urinary excretion
      of the parent drug was low, with less than 1% of the administered dose excreted
      in urine after i.v. infusion in monkeys at clinically relevant doses (< or = 5
      mg/kg). ISIS 104838 is highly bound to plasma proteins, likely preventing renal
      filtration. However, shortened oligonucleotide metabolites of ISIS 104838 lose
      their affinity to bind plasma proteins. Thus, excretion of radiolabel (mostly as
      metabolites) in urine (75%) and feces (5-10%) was nearly complete by 90 days.
      Elimination of ISIS 104838 from tissue was slow (multiple days) for all species,
      depending on the tissue or organ. The highest concentrations of ISIS 104838 in
      tissues were seen in kidney, liver, lymph nodes, bone marrow, and spleen. In
      general, concentrations of ISIS 104838 were higher in monkey tissues than in
      rodents at body weight-equivalent doses. Plasma pharmacokinetics scale well
      across species as a function of body weight alone. This favorable pharmacokinetic
      profile for ISIS 104838 provides guidance for clinical development and appears to
      support infrequent and convenient dose administration.

PMID- 14570777
TI  - Bioactivation of the 3-amino-6-chloropyrazinone ring in a thrombin inhibitor
      leads to novel dihydro-imidazole and imidazolidine derivatives: structures and
      mechanism using 13C-labels, mass spectrometry, and NMR.
AB  - Thrombin is a serine protease that plays a key role in the blood coagulation
      cascade. Compound I [2-[6-chloro-3-[(2,2-difluoro-2-pyridin-2-ylethyl)amino]-2
      oxopyrazin-1(2H)-yl]-N-[(3-fluoropyridin-2-yl)methyl]acetamide] is a potent,
      selective, and orally bioavailable thrombin inhibitor that is being studied as a
      possible anticoagulant. Biotransformation studies in rats revealed that 84% of an
      i.v. dose of I was excreted in the form of two metabolites. Both metabolites were
      formed by metabolic activation of the pyrazinone ring in I and subsequent
      rearrangement leading to two novel dihydro-imidazole and imidazolidine
      derivatives. The structures of these metabolites and their mechanism of formation
      were elucidated by additional use of two 13C single labels in the pyrazinone ring
      of I in combination with mass spectrometry and NMR techniques. The metabolite
      structures described here illustrate the rich metabolic chemistry of the amino
      pyrazinone heterocycle.

PMID- 14570778
TI  - Pharmacokinetics and metabolism of [14C]eplerenone after oral administration to
      humans.
AB  - A pharmacokinetics and metabolism study was conducted in eight healthy human
      volunteers. After oral administration of [14C]eplerenone (EP) at a dose of 100 mg
      per person as an aqueous solution, blood, saliva, breath, urine, and fecal
      samples were collected at various time points. All matrices were analyzed for
      total radioactivity and/or for EP and its open-lactone-ring form (EPA). EP was
      well absorbed, and a mean EP Cmax of 1.72 mug/ml was achieved 1.2 h postdose.
      After the Cmax, plasma concentrations of EP declined with a half-life of 3.0 h.
      Plasma concentrations of EPA were much lower than EP concentrations, and the area
      under the plasma-concentration time curve (AUC) for EPA was only 4% of the EP
      AUC. Plasma protein binding was moderate (33-60%) but concentration-dependent
      over the therapeutic concentration range. EP and its metabolites did not
      preferentially partition into the red blood cells and blood concentrations of
      total radioactivity were lower than plasma concentrations. Approximately 66.6%
      and 32.0% of the radioactive dose were excreted in urine and feces, respectively.
      The majority of urinary and fecal radioactivity was due to metabolites,
      indicating extensive metabolism of EP. The major metabolic pathways were 6beta-
      and/or 21-hydroxylation and 3-keto reduction. There was no evidence for any
      alteration of the 9,11-epoxide ring or the methyl ester. As a percentage of dose,
      the primary metabolic products excreted in urine and feces included 6beta-hydroxy
      EP (6beta-OHEP) (32.0%), 6beta,21-OHEP (20.5%), 21-OHEP (7.89%), and
      2alpha,3beta,21-OHEP (5.96%). The amounts of the other metabolites excreted were
      less than 5% each.

PMID- 14570779
TI  - A method for identification of inhibition mechanism and estimation of Ki in in
      vitro enzyme inhibition study.

PMID- 14570780
TI  - Should perioperative management target oxygen delivery?

PMID- 14570781
TI  - Effect of adding dopexamine to intraoperative volume expansion in patients
      undergoing major elective abdominal surgery.
AB  - BACKGROUND: The contribution of low-dose dopexamine to outcome, when given to
      increase cardiac output in patients already treated with fluids during major
      abdominal surgery, is not yet known. METHOD: We carried out a randomized double
      blind placebo-controlled trial. All 100 patients studied were given fluid
      infusions during surgery guided by stroke volume measurements made with an
      oesophageal Doppler probe. Patients were randomized to receive dopexamine at the
      rate of 0.25 microg kg(-1) min(-1) or saline 0.9% (control) for the first 24 h
      after the start of surgery. The primary outcome measure was the incidence of
      postoperative morbidity. RESULTS: There were no statistically significant
      differences between groups in the incidence of postoperative complications, the
      length of hospital stay, the incidence of morbidity and the use of critical care
      facilities. The patients randomized to receive dopexamine had significantly more
      pre-existing disease than the control patients. Mortality in both groups was
      significantly less than predicted by the POSSUM (Physiological and Operative
      Severity Score for the enUmeration of Mortality and morbidity) risk prediction
      score. CONCLUSION: We could not demonstrate an advantage to using low-dose
      dopexamine in high-risk patients during major abdominal surgery.

PMID- 14570782
TI  - Safety of human albumin--serious adverse events reported worldwide in 1998-2000.
AB  - BACKGROUND: Previous pharmacovigilance studies have indicated a low rate of
      adverse events in patients receiving human albumin. However, the incidence of
      adverse events is likely to have been underestimated because of under-reporting.
      A more accurate estimate may be possible during a period such as 1998-2000, when
      awareness regarding albumin safety was heightened by publication of a meta
      analysis. METHODS: All serious adverse event reports received, and total doses of
      albumin distributed worldwide from the beginning of 1998 to the end of 2000 by 10
      major suppliers of therapeutic human albumin were compiled. RESULTS: Distributed
      albumin doses totalled 1.62 x 10(7). The total numbers of non-fatal and fatal
      serious adverse events reported were 198 and 13, respectively. The incidence of
      all reported serious non-fatal and fatal adverse events was 5.28 per 10(6) doses
      (CI 1.60-17.4 per 10(6) doses). For non-fatal serious adverse events only, the
      observed incidence was 4.65 per 10(6) doses (CI 1.34-16.2 per 10(6) doses). No
      patient death was classified as probably related to albumin administration. The
      observed incidence of fatal serious adverse events possibly related to albumin
      was 0.185 per 10(6) doses (CI 0.0597-0.574 per 10(6) doses). The observed
      incidence of all non-fatal and fatal serious adverse events was significantly
      higher during the 1998-2000 period as compared with 1990-1997 (incidence rate
      ratio 4.98; CI 3.94-6.29), probably chiefly as a result of reduced under
      reporting. CONCLUSIONS: Although the observed incidence of adverse events is
      likely to be an underestimate, nevertheless both non-fatal and fatal serious
      adverse events in albumin recipients appear to be rare. These results add further
      support to the excellent safety record of human albumin.

PMID- 14570783
TI  - Patient well-being after general anaesthesia: a prospective, randomized,
      controlled multi-centre trial comparing intravenous and inhalation anaesthesia.
AB  - BACKGROUND: The aim of this study was to assess postoperative patient well-being
      after total i.v. anaesthesia compared with inhalation anaesthesia by means of
      validated psychometric tests. METHODS: With ethics committee approval, 305
      patients undergoing minor elective gynaecologic or orthopaedic interventions were
      assigned randomly to total i.v. anaesthesia using propofol or inhalation
      anaesthesia using sevoflurane. The primary outcome measurement was the actual
      mental state 90 min and 24 h after anaesthesia assessed by a blinded observer
      using the Adjective Mood Scale (AMS) and the State-Trait-Anxiety Inventory
      (STAI). Incidence of postoperative nausea and vomiting (PONV) and postoperative
      pain level were determined by Visual Analogue Scale (VAS) 90 min and 24 h after
      anaesthesia (secondary outcome measurements). Patient satisfaction was evaluated
      using a VAS 24 h after anaesthesia. RESULTS: The AMS and STAI scores were
      significantly better 90 min after total i.v. anaesthesia compared with inhalation
      anaesthesia (P=0.02, P=0.05, respectively), but equal 24 h after both anaesthetic
      techniques (P=0.90, P=0.78, respectively); patient satisfaction was comparable
      (P=0.26). Postoperative pain was comparable in both groups 90 min and 24 h after
      anaesthesia (P=0.11, P=0.12, respectively). The incidence of postoperative nausea
      was reduced after total i.v. compared with inhalation anaesthesia at 90 min (7 vs
      35%, P<0.001), and 24 h (33 vs 52%, P=0.001). CONCLUSION: Total i.v. anaesthesia
      improves early postoperative patient well-being and reduces the incidence of
      PONV.

PMID- 14570784
TI  - Optimization of desflurane administration in morbidly obese patients: a
      comparison with sevoflurane using an 'inhalation bolus' technique.
AB  - BACKGROUND: The concept of an 'inhalation bolus' can be used to optimize inhaled
      drug administration. We investigated the depth of anaesthesia, haemodynamic
      stability, and recovery time in morbidly obese patients resulting from bispectral
      index (BIS)-guided sevoflurane or desflurane administration and BIS-triggered
      inhalation boluses of sevoflurane or desflurane combined with titration of
      remifentanil. METHODS: Fifty morbidly obese patients undergoing laparoscopic
      gastroplasty received either BIS-guided sevoflurane or desflurane anaesthesia in
      combination with a remifentanil target-controlled infusion. Intraoperative
      haemodynamic stability and BIS control were measured. Immediate recovery was
      recorded. RESULTS: Intraoperatively, the BIS was between 40 and 60 for a greater
      percentage of time in the sevoflurane (78 (13)% of case time) than in the
      desflurane patients (64 (14)% of case time), owing to too profound anaesthesia in
      the desflurane patients at the start of the procedure. However, fewer episodes of
      hypotension were found in the desflurane group, without the occurrence of more
      hypertensive episodes. During immediate recovery, eye opening, extubation, airway
      maintenance, and orientation occurred sooner in the desflurane group.
      CONCLUSIONS: Immediate recovery was significantly faster in the desflurane group.
      Overall hypnotic controllability measured by BIS was less accurate with
      desflurane. Overall haemodynamic controllability was better when using
      desflurane. Fewer episodes of hypotension were found in the desflurane group. The
      use of the inhalation bolus was found to be appropriate in both groups without
      causing severe haemodynamic side effects. Minimal BIS values were significantly
      lower after a desflurane bolus.

PMID- 14570785
TI  - Activation of electrocorticographic activity with remifentanil and alfentanil
      during neurosurgical excision of epileptogenic focus.
AB  - BACKGROUND: Opioids are known to stimulate surface electroencephalographic
      activity in patients with temporal lobe epilepsy. The objective of the current
      study was to compare the electrocorticographic activation effects of the newer
      short-acting opioid remifentanil with those of alfentanil during epilepsy surgery
      under general anaesthesia. METHODS: Thirteen patients undergoing temporal lobe
      epilepsy surgery under general anaesthesia received alfentanil 30 microg kg(-1)
      and remifentanil 1 microg kg(-1) as i.v. boluses in sequence. The design was a
      randomized double-blind cross-over study. After opening the dura,
      electrocorticogram (ECoG) electrode contact strips were placed over the temporal
      and supratemporal neocortex and depth electrodes were inserted in the amygdala
      and hippocampus. Alfentanil 30 microg kg(-1) or remifentanil 1 microg kg(-1) were
      administered randomly in a blinded fashion. The ECoG was recorded continuously
      before and after the injection of each drug. The interictal epileptiform activity
      (spikes and sharp waves) above baseline was analysed. RESULTS: Both drugs
      increased epileptiform activity especially that recorded from depth electrodes in
      the temporal limbic structures. No epileptiform activity was recorded from the
      electrodes overlying the supratemporal neocortex before or after drug
      administration. The more potent activator was alfentanil, which caused an
      increase in activation from baseline of 99.8% compared with 67.4% for
      remifentanil. In addition, alfentanil activated the epileptiform activity in 3
      patients in which remifentanil had no effect. There were no changes in heart rate
      after the opioid boluses. Both remifentanil and alfentanil caused significant
      reductions in blood pressure at 3 and 5 min after administration. CONCLUSION: We
      conclude that at the doses used in this study, alfentanil is the better opioid
      for intraoperative activation of the ECoG in neurosurgical patients undergoing
      resection of a temporal lobe epileptic focus. This pharmacological activation of
      epileptiform activity assists in localizing and confirming the site of surgical
      excision. Neither alfentanil nor remifentanil activated epileptiform activity in
      non-epileptic brain tissue.

PMID- 14570786
TI  - Cerebral embolization during cardiac surgery: impact of aortic atheroma burden.
AB  - BACKGROUND: Aortic atheromatous disease is known to be associated with an
      increased risk of perioperative stroke in the setting of cardiac surgery. In this
      study, we sought to determine the relationship between cerebral microemboli and
      aortic atheroma burden in patients undergoing cardiac surgery. METHODS:
      Transoesophageal echocardiographic images of the ascending, arch and descending
      aorta were evaluated in 128 patients to determine the aortic atheroma burden.
      Transcranial Doppler (TCD) of the right middle cerebral artery was performed in
      order to measure cerebral embolic load during surgery. Using multivariate linear
      regression, the numbers of emboli were compared with the atheroma burden.
      RESULTS: After controlling for age, cardiopulmonary bypass time and the number of
      bypass grafts, cerebral emboli were significantly associated with atheroma in the
      ascending aorta (R2=0.11, P=0.02) and aortic arch (P=0.013). However, there was
      no association between emboli and descending aortic atheroma burden (R2=0.05,
      P=0.20). CONCLUSIONS: We demonstrate a positive relationship between TCD-detected
      cerebral emboli and the atheromatous burden of the ascending aorta and aortic
      arch. Previously demonstrated associations between TCD-detectable cerebral emboli
      and adverse cerebral outcome may be related to the presence of significant aortic
      atheromatous disease.

PMID- 14570787
TI  - Nociceptive and anaesthetic-induced changes in pulse transit time during general
      anaesthesia.
AB  - BACKGROUND: Pulse transit time (rPTT), the interval between ventricular
      electrical activity and arrival of a peripheral pulse waveform, has been used to
      detect changes in autonomic tone. The aim of this observational pilot study was
      to measure changes in rPTT in response to general anaesthesia and noxious
      stimuli. METHODS: Thirty-one healthy women undergoing gynaecological surgery were
      allocated to groups depending on the need for airway management with tracheal
      intubation (n=9), a laryngeal mask (LMA, n=17) or a facemask (n=5). During
      general anaesthesia, we measured changes in RR interval (RR-int) and rPTT after
      (i) induction of anaesthesia, (ii) airway manipulation and (iii) surgical
      stimulus. rPTT was estimated as the interval from the peak in the R-wave to
      detection of the pulse oximeter waveform in the periphery. RESULTS: Mean baseline
      rPTT was 245 (SD 27) ms. Upon induction of anaesthesia, rPTT increased (by 28.2
      (20.4) ms, P<0.001) in all but two patients. rPTT decreased in response to
      endotracheal intubation (by 43.1 (24.6) ms, P=0.001) but did not vary in response
      to insertion of LMA or surgical stimulus. Mean baseline RR-int was 865 (141) ms.
      A mean reduction in RR-int after tracheal intubation did not reach statistical
      significance. RR-int was unchanged with induction of anaesthesia, LMA insertion
      or surgical stimulus. CONCLUSION: Variation in rPTT reflects autonomic responses
      to nociceptive stimulation and fluctuations in anaesthetic depth independently of
      heart rate.

PMID- 14570788
TI  - Cardiovascular changes after the three stages of nasotracheal intubation.
AB  - BACKGROUND: Nasotracheal intubation typically comprises three distinct stages:
      (i) nasopharyngeal intubation; (ii) direct laryngoscopy to identify the vocal
      cords; and (iii) the passage of the tracheal tube into the trachea. The aim of
      this study was to identify and compare the cardiovascular responses associated
      with each of these stages. METHODS: Seventy-five ASA I or II patients, aged 16-65
      yr, requiring nasotracheal intubation as part of their anaesthetic management,
      received a standardized general anaesthetic and were allocated randomly to
      receive either nasopharyngeal intubation or nasopharyngeal intubation plus direct
      laryngoscopy or full nasotracheal intubation. RESULTS: There was a significant
      hypertensive response, compared with pre-induction levels, in all three groups.
      The maximum mean (SD) mean arterial pressure in the nasotracheal intubation group
      was 113 (17.1) mm Hg, which was significantly greater than that in the
      nasopharyngeal intubation (97 (13) mm Hg) (P<0.001) and in the nasopharyngeal
      intubation plus laryngoscopy (103 (10.3) mm Hg) (P=0.007) groups. There was no
      significant difference between the nasopharyngeal intubation and nasopharyngeal
      intubation plus laryngoscopy groups (P=0.206). A similar pattern was seen for
      both systolic and diastolic arterial pressure. Nasotracheal intubation caused a
      significant increase in maximum mean (SD) heart rate, compared with pre-induction
      values, whereas the other two groups caused significant falls. The heart rate in
      the nasotracheal intubation group (92 (16.5) beats min(-1)) was significantly
      greater than in the other two groups (74 (8.6) (P<0.001) and 76 (12) (P<0.001)
      beats min(-1) respectively). There was no significant difference in heart rates
      between the nasopharyngeal intubation and nasopharyngeal intubation plus
      laryngoscopy groups (P=0.420). CONCLUSIONS: Nasopharyngeal intubation causes a
      significant pressor response. Stimulation of the larynx and trachea by the
      passage of the tracheal tube, but not direct laryngoscopy, causes a significant
      increase in this response.

PMID- 14570789
TI  - Randomized comparison of the classic Laryngeal Mask Airway with the Airway
      Management Device during anaesthesia.
AB  - BACKGROUND: We compared the modified Airway Management Device (AMD) with the
      classic Laryngeal Mask Airway (cLMA) in a randomized comparative trial. METHODS:
      Primary outcome was success of airway placement. Secondary outcomes included time
      to achieve an airway, airway manipulations required, complications during use and
      fibre-optic assessment of airway positioning. RESULTS: We planned to study 300
      patients but interim analysis demonstrated the study should be stopped after 100
      patients. The AMD was inserted on the first attempt less frequently than the cLMA
      (P=0.04). Eight AMDs and one cLMA could not be placed within three attempts
      (P=0.03). The AMD required more attempts (P=0.03) and more manipulations (P=0.02)
      and caused more complications (P=0.01) during insertion. During maintenance of
      anaesthesia, three AMDs and no cLMAs had to be removed as a result of
      complications. Seal pressure was better with the AMD than with the cLMA (AMD 25
      cm H2O, cLMA 20 cm H2O, P=0.001). Efficacy of ventilation was better with the
      cLMA than with the AMD (P=0.005). On fibre-optic examination, positioning over
      the larynx was better with the cLMA than with the AMD (P=0.005). Two of 32
      attempts to pass an orogastric tube via the AMD were successful. During recovery,
      two AMDs and no cLMAs required premature removal. Tolerance during emergence, the
      incidence of blood on the devices and the incidence of postoperative
      complications were equivalent between devices. Overall failure rate of the AMD
      was greater than that of the cLMA (P=0.001). CONCLUSIONS: Successful insertion of
      the cLMA is more likely than that of the AMD. Insertion of the AMD required more
      attempts and caused a greater number of complications. Fibre-optic position was
      poorer than with the cLMA. When an airway is established, the AMD caused a
      greater number of complications during anaesthesia and failed more frequently
      than the cLMA. During recovery from anaesthesia, more complications occurred with
      the AMD. Overall performance of the AMD was poorer than with the classic LMA.

PMID- 14570790
TI  - Randomized crossover comparison of the ProSeal laryngeal mask airway with the
      Laryngeal Tube during anaesthesia with controlled ventilation.
AB  - BACKGROUND: The Laryngeal Tube (LT) performs similarly to the classic laryngeal
      mask airway during controlled ventilation but with an improved airway seal. We
      compared the laryngeal tube with the ProSeal laryngeal mask airway (PLMA)
      throughout anaesthesia. METHODS: Thirty-two patients were studied using a
      randomized cross-over design. The primary outcome measure was airway seal
      pressure. Secondary outcome measures included peak and plateau airway pressures,
      time to achieve an airway, ease of insertion, airway manipulations required to
      achieve a patent airway and grade of fibre-optic laryngoscopy. The proportion of
      patients in whom good, fair or failed ventilation was achieved was also
      calculated. RESULTS: No significant difference was found in regard to seal
      pressure (PLMA, median 26.5 cm H2O, range 10-40; LT, median 24, range 6-40;
      P=0.7, 95% confidence interval of the difference 3.5 to -4.0). There were two
      failures of insertion or ventilation in the LT group and none in the PLMA group.
      The peak airway pressure with the PLMA was lower than with the LT but the
      difference was clinically unimportant (PLMA, mean 16.2 cm H2O, SD 3.52; LT, mean
      17.9, SD 5.21; P=0.02, 95% confidence interval of the difference -3.1 to -0.28).
      The PLMA took significantly less time to insert than the LT (PLMA, median 18.5 s,
      interquartile range 14-26; LT, median 22, interquartile range 15-36.5; P<0.02,
      95% confidence interval of the difference -21.5 to -1.0). The PLMA gave a
      significantly better view on fibre-optic laryngoscopy than the LT (P<0.001, 95%
      confidence interval of the difference in grade -2.0 to -1.0). In the 16 patients
      in whom the PLMA was used during maintenance of anaesthesia ventilation was good
      in 15, fair in none and failed in one. The equivalent figures for the LT were
      good in nine, fair in six and failed in one (P=0.009). There was no significant
      difference in the plateau airway pressure, ease of insertion of the devices,
      number of manipulations required to achieve or maintain an airway, or in overall
      complications. CONCLUSION: The two devices performed equally well in terms of
      seal pressure. The PLMA was quicker to insert. Efficacy of ventilation was
      significantly better with the PLMA than the LT. The PLMA allowed a significantly
      better view of the larynx with a fibre-optic laryngoscope, and may therefore be
      of more use in cases where visualization of the larynx is required.

PMID- 14570791
TI  - Comparison of the effects of intrathecal ropivacaine, levobupivacaine, and
      bupivacaine for Caesarean section.
AB  - BACKGROUND: This study aimed to detect if intrathecal (i.t.) ropivacaine and
      levobupivacaine provided anaesthesia (satisfactory analgesia and muscular
      relaxation) and postoperative analgesia of similar quality to bupivacaine in
      patients undergoing Caesarean section. METHODS: Ninety parturients were enrolled.
      A combined spinal-epidural technique was used. Patients were randomly assigned to
      receive one of the following isobaric i.t. solutions: bupivacaine 8 mg (n=30),
      levobupivacaine 8 mg (n=30), or ropivacaine 12 mg (n=30), all combined with
      sufentanil 2.5 microg. An i.t. solution was considered effective if an upper
      sensory level to pinprick of T4 or above was achieved and if intraoperative
      epidural supplementation was not required. Sensory changes and motor changes were
      recorded. RESULTS: Anaesthesia was effective in 97, 80, and 87% of patients in
      the bupivacaine 8 mg, levobupivacaine 8 mg, and ropivacaine 12 mg groups,
      respectively. Bupivacaine 8 mg was associated with a significantly superior
      success rate to that observed in the levobupivacaine group (P<0.05). It also
      provided a longer duration of analgesia and motor block (P<0.05 vs
      levobupivacaine and ropivacaine). CONCLUSIONS: The racemic mixture of bupivacaine
      combined with sufentanil remains an appropriate choice when performing Caesarean
      sections under spinal anaesthesia.

PMID- 14570792
TI  - Epidural versus intrathecal morphine for postoperative analgesia after Caesarean
      section.
AB  - BACKGROUND: Perispinal anaesthesia for Caesarean section allows injection of
      epidural (ED) or intrathecal (i.t.) morphine to provide long-lasting
      postoperative analgesia. To compare these two routes, a prospective, randomized,
      double-blinded study of 53 patients undergoing elective Caesarean section was
      performed. METHODS: Combined spinal-epidural anaesthesia with 6 mg of i.t.
      hyperbaric bupivacaine plus sufentanil 5 microg, and additional ED lidocaine was
      used. Additionally, each patient received either 2 mg (2 ml) of ED morphine plus
      1 ml of i.t. normal saline (ED group, n=28), or 0.075 mg (1 ml) of i.t. morphine
      plus 2 ml of ED normal saline (i.t. group, n=25). Additional postoperative
      analgesia was given in the form of propacetamol and ketoprofen, plus self
      administered i.v. morphine. RESULTS: No major respiratory depression occurred.
      Time to first demand of morphine was similar in the ED (307.5 min) and i.t. (310
      min) groups, as was the incidence of side-effects such as sedation, pruritus,
      nausea, and vomiting. During the first 24 postoperative hours, VAS pain scores
      were greater in the i.t. group (P=0.032), as was additional morphine consumption
      (4 vs 1.5 mg) (P=0.03). CONCLUSIONS: The ED protocol was more effective than the
      i.t. protocol, whilst side-effects were similar.

PMID- 14570793
TI  - Sequential compression device with thigh-high sleeves supports mean arterial
      pressure during Caesarean section under spinal anaesthesia.
AB  - BACKGROUND: This study investigated the use of a Sequential Compression Device
      (SCD) with thigh-high sleeves and a preset pressure of 50 mm Hg that recruits
      blood from the lower limbs intermittently, as a method to prevent spinal
      hypotension during elective Caesarean section. Possible association of arterial
      pressure changes with maternal, fetal, haemodynamic, and anaesthetic factors were
      studied. METHODS: Fifty healthy parturients undergoing elective Caesarean section
      under spinal anaesthesia were randomly assigned to either SCD (n=25) or control
      (n=25) groups. A standardized protocol for pre-hydration and anaesthetic
      technique was followed. Hypotension was defined as a decrease in any mean
      arterial pressure (MAP) measurement by more than 20% of the baseline MAP.
      Systolic (SAP), MAP and diastolic (DAP) arterial pressure, pulse pressure (PP),
      and heart rate (HR) were noted at baseline and every minute after the spinal
      block until delivery. RESULTS: A greater than 20% decrease in MAP occurred in 52%
      of patients in the SCD group vs 92% in the control group (P=0.004, odds ratio
      0.094, 95% CI 0.018-0.488). There were no significant differences in SAP, DAP,
      HR, and PP between the groups. CONCLUSION: SCD use in conjunction with
      vasopressor significantly reduced the incidence of a 20% reduction of MAP.

PMID- 14570794
TI  - Lung density distribution in dynamic CT correlates with oxygenation in ventilated
      pigs with lavage ARDS.
AB  - BACKGROUND: Fast dynamic computed tomography (dCT) has been used to assess
      regional dynamics of lung inflation and deflation processes. The aim of this
      study was to relate ventilation-induced changes in lung density distribution, as
      measured over several respiratory cycles by dCT, to oxygenation and shunt
      fraction in a lavage acute respiratory distress syndrome model. METHODS: Six
      anaesthetized pigs underwent pressure-constant ventilation (FIO2=1.0,
      inspiratory:expiratory ratio=1:1) before and after induction of lung damage by
      saline lavage. Mean airway pressure (Paw) was varied (8, 13, 18, 23, 28, 33, and
      38 cm H2O) in random order. At each Paw level, dCT acquisitions were performed
      over several respiratory cycles (Somatom Plus4, Siemens; supradiaphragmatic
      transverse slice; thickness=1 mm; temporal resolution=100 ms). During scanning at
      each Paw, arterial and mixed venous blood were obtained for blood gas analysis
      and shunt calculation. In each CT image, fractional areas (FA) of defined density
      ranges representing ventilated lung and atelectasis were determined by planimetry
      using dedicated software. The FA data of individual 100 ms scans were averaged
      over several respiratory cycles, and expressed as mean FA in percentage of total
      lung area at each Paw. For atelectatic lung parenchyma a quantitative
      relationship of the respective mean FA to shunt fraction was studied using
      regression analysis. RESULTS: Under steady-state conditions, mean FA of
      atelectasis correlated linearly with the calculated shunt fraction (healthy
      lungs, r=+0.76; lavaged lungs, r=+0.89). There is a non-linear relationship
      between mean FA of ventilated lung parenchyma and mean FA of atelectasis with
      PaO2. CONCLUSIONS: We conclude that dCT allows assessment of the effects of
      ventilator adjustments and resultant Paw; changes upon lung aeration and
      oxygenation rapidly, and with good spatial and temporal resolution. This may
      benefit patients with acute lung injury, whose ventilatory pattern may be
      optimized as early as during their first diagnostic workup.

PMID- 14570795
TI  - Xenon: no stranger to anaesthesia.

PMID- 14570796
TI  - Post-dural puncture headache: pathogenesis, prevention and treatment.
AB  - Spinal anaesthesia developed in the late 1800s with the work of Wynter, Quincke
      and Corning. However, it was the German surgeon, Karl August Bier in 1898, who
      probably gave the first spinal anaesthetic. Bier also gained first-hand
      experience of the disabling headache related to dural puncture. He correctly
      surmised that the headache was related to excessive loss of cerebrospinal fluid
      (CSF). In the last 50 yr, the development of fine-gauge spinal needles and needle
      tip modification, has enabled a significant reduction in the incidence of post
      dural puncture headache. Though it is clear that reducing the size of the dural
      perforation reduces the loss of CSF, there are many areas regarding the
      pathogenesis, treatment and prevention of post-dural puncture headache that
      remain contentious. How does the microscopic pattern of collagen alignment in the
      spinal dura affect the dimensions of the dural perforation? How do needle design,
      size and orientation influence leakage of CSF through the dural perforation? Can
      pharmacological methods reduce the symptoms of post-dural puncture headache? By
      which mechanism does the epidural blood patch cure headache? Is there a role for
      the prophylactic epidural blood patch? Do epidural saline, dextran, opioids and
      tissue glues reduce the rate of CSF loss? This review considers these contentious
      aspects of post-dural puncture headache.

PMID- 14570797
TI  - A novel method of deriving the effect compartment equilibrium rate constant for
      propofol.
AB  - BACKGROUND: Calculation of the effect compartment concentration (Ce) in non
      steady-state conditions requires the equilibrium rate constant, keo. Most studies
      of propofol derive the keo using EEG measurements. This study investigated an
      alternative method. Starting from a predicted concentration-time profile, a keo
      value was included so that the predicted Ce at a specific pharmacodynamic end
      point was the same when using three different methods of injection. METHODS:
      Seventy-five patients were given propofol for induction of anaesthesia. Twenty
      five patients received a single bolus, 25 patients received an infusion, and 25
      patients received a bolus followed by an infusion. Computer simulation was used
      to derive the central compartment concentration. The keo that brought about the
      same value for Ce at loss of the eyelash reflex using the three methods of
      injection was derived. RESULTS: Keo was found to be 0.80 min(-1). Mean (SD) Ce at
      loss of the eyelash reflex was 2.27 (0.69) microg ml(-1). CONCLUSIONS: The effect
      compartment equilibrium rate constant and concentration at loss of the eyelash
      reflex can be derived without the use of electronic central nervous system
      monitors.

PMID- 14570798
TI  - Spread of injectate with superficial cervical plexus block in humans: an
      anatomical study.
AB  - BACKGROUND: This study was undertaken to investigate why the superficial cervical
      plexus block for carotid endarterectomy is so effective. Initial consideration
      would suggest that a superficial injection would be unlikely to block all
      terminal fibres of relevant nerves. One possibility is that the local anaesthetic
      crosses the deep cervical fascia and blocks the cervical nerves at their roots.
      METHODS: Superficial cervical plexus blocks (injections just below the investing
      fascia) were performed using methylene blue (30 ml) in four cadavers. In one
      additional control cadaver, a deep cervical plexus injection was performed. In a
      second control cadaver, a subcutaneous injection (superficial to investing
      fascia) was performed at the posterior border of the sternomastoid muscle.
      RESULTS: Anatomical dissection showed that with superficial block there was
      spread of the dye to structures beneath the deep cervical fascia. In the first
      control, dye remained in the deep cervical space. In the second control, dye
      remained subcutaneous. CONCLUSIONS: The superficial cervical space communicates
      with the deep cervical space and this may explain the efficacy of the superficial
      block. The method of communication remains unknown. Our findings also indicate
      that the suitable site of injection for the superficial cervical plexus block is
      below the investing fascia of the neck, and not just subcutaneous.

PMID- 14570799
TI  - Breathing gas perfluorocarbon measurements using an absorber filled with
      zeolites.
AB  - BACKGROUND: Perfluorocarbon (PFC) has been widely used in the treatment of
      respiratory diseases; however, PFC content of the breathing gases remains
      unknown. Therefore, we developed an absorber using PFC selective zeolites for PFC
      measurement in gases and investigated its accuracy. METHODS: To generate a
      breathing gas with different PFC contents a heated flask was rinsed with a
      constant air flow of 4 litre x min(-1) and 1, 5, 10, and 20 ml of PFC were
      infused over 20 min using an infusor. The absorber was placed on an electronic
      scale and the total PFC volume was calculated from the weight gain. RESULTS:
      Steady-state increase in weight was achieved 3.5 min after stopping the infusion.
      The calculated PFC volume was slightly underestimated but the measuring error did
      not exceed -1% for PFC less than 1 ml. The measurement error decreased with
      increasing PFC volume. CONCLUSIONS: This zeolite absorber is an accurate method
      to quantitatively determine PFC in breathing gases and can be used as a reference
      method to validate other PFC sensors.

PMID- 14570800
TI  - Pulmonary thromboendarterectomy in a case of hereditary stomatocytosis.
AB  - We present a case of pulmonary thromboendarterectomy performed successfully in a
      patient with stomatocytosis. Stomatocytosis is a rare condition of abnormal
      erythrocyte morphology in which haemolysis and hyperkalaemia occur at cooler
      temperatures. A 35-yr-old male with stomatocytosis was referred for pulmonary
      thromboendarterectomy in the context of chronic thromboembolic pulmonary
      hypertension. He had undergone splenectomy as a child, which rendered him
      hypercoagulable as the spleen normally removes the haemolysed red cell fragments
      from blood. By constantly monitoring urine for macroscopic haematuria, arterial
      and mixed venous blood gas analysis perioperatively and by limiting the period of
      deep hypothermic circulatory arrest that is normally required for this operation,
      we were able to perform the operation successfully.

PMID- 14570801
TI  - Temporary cardiopulmonary bypass and isolated lung ventilation for tracheal
      stenosis and reconstruction.
AB  - A 27-yr-old lady with a past history of prolonged ventilation presented with
      worsening respiratory distress caused by tracheal stenosis. She required urgent
      tracheal resection and reconstruction. Because of the risk of an acute
      respiratory obstruction, spinal anaesthesia was used to establish cardiopulmonary
      bypass by cannulating the femoral artery and femoral vein. Adequate gas exchange
      was possible with full flow rate. Thoracotomy was then carried out to mobilize
      the left main bronchus. After successfully securing an airway by intubation of
      the left main bronchus, cardiopulmonary bypass was discontinued and tracheal
      resection and anastomosis was done under conventional one lung anaesthesia.

PMID- 14570802
TI  - Anaesthetic management of coronary artery bypass grafting in a patient with
      central core disease and susceptibility to malignant hyperthermia on statin
      therapy.
AB  - Central core disease and malignant hyperthermia (MH) are both associated with
      mutations in the RYR1 gene. We report the anaesthetic management of one such
      patient presenting for coronary artery bypass grafting. Her medication included
      aspirin 75 mg, atorvastatin 20 mg, isosorbide mononitrate 60 mg, atenolol 25 mg
      and glyceryl trinitrite sublingual spray as required. The use of aprotinin,
      statins and moderate hypothermia in patients with central core disease and known
      susceptibility to MH has not been documented.

PMID- 14570803
TI  - Complete heart block during central venous catheter placement in a patient with
      pre-existing left bundle branch block.
AB  - Heart block and arrhythmia are complications of pulmonary artery and cardiac
      catheterization. Injury to the conducting system of the heart often involves the
      right bundle causing right bundle branch block (RBBB). If patients already have
      left bundle branch block (LBBB), complete heart block (CHB) may result. After
      trauma, impairment of the right bundle is usually transient with recovery in
      hours, but complete heart block can lead to symptoms requiring invasive
      treatment. Similar complications are rare with insertion of central venous
      catheters, as they should not enter the heart. Injury to the right bundle during
      central venous catheter insertion can be by trauma from the guide wire or from
      the catheter itself. The function of the AV node and bundle of His in these
      patients has not been studied before. We report a patient with LBBB who developed
      CHB during insertion of a central venous cannula. Conduction through the AV node
      and His-Purkinje system was intact, showing that the transient RBBB was caused by
      traumatic injury rather than by other disease of the conduction system.

PMID- 14570804
TI  - Decreased bispectral index as an indicator of syncope before hypotension and
      bradycardia in two patients with needle phobia.
AB  - We report two cases who exhibited a decrease in their bispectral index (BIS)
      score, associated with syncope during venipuncture in patients with suspected
      needle phobia. In case 1, the reduction in BIS score occurred during the
      development of hypotension and bradycardia and may well have been caused by
      cerebral hypoperfusion. In case 2, the patient lost consciousness with decreasing
      BIS score before hypotension and bradycardia; this patient's condition could not
      be completely explained by cerebral hypoperfusion as a result of a vasovagal
      reflex because the patient's blood pressure and heart rate remained normal during
      the syncopal episode.

PMID- 14570805
TI  - Use of the ProSeal laryngeal mask airway in a pregnant patient with a difficult
      airway during electroconvulsive therapy.
AB  - We describe a patient at 20-22 weeks gestation, with a known difficult airway,
      who underwent eight sessions of electroconvulsive therapy using the ProSeal
      laryngeal mask airway and controlled ventilation. The airway management options
      for brief periods of general anaesthesia in patients with increased gastric
      volume are discussed.

PMID- 14570806
TI  - Genes and outcome from anaesthesia.

PMID- 14570807
TI  - SIRS--a syndrome, disease or a chef d'oeuvre?

PMID- 14570808
TI  - Intubation times for using the Bonfils intubation fibrescope.

PMID- 14570809
TI  - TMJ assessment before anaesthesia.

PMID- 14570810
TI  - Avoiding oesophageal ventilation with the intubating laryngeal mask airway:
      predictive value of the air aspiration test compared with capnography.

PMID- 14570811
TI  - Simple tracheal tube--an alternative to the modified nasal trumpet.

PMID- 14570812
TI  - Air embolism--a complication of percutaneous nephrolithotripsy.

PMID- 14570813
TI  - Early extubation after two-stage oesophagectomy.

PMID- 14570814
TI  - Caudal neostigmine in children.

PMID- 14570815
TI  - Postdural puncture tinnitus.

PMID- 14570816
TI  - Changes in cerebral perfusion precede plaque formation in multiple sclerosis: a
      longitudinal perfusion MRI study.
AB  - New MRI techniques such as the analysis of magnetization transfer or diffusion
      have provided evidence for subtle progressive alterations in tissue integrity
      prior to focal leakage of the blood-brain barrier (BBB) as part of plaque
      formation in multiple sclerosis. Since inflammation is capable of modulating the
      microcirculation, we investigated the hypothesis that changes in the local
      perfusion might be one of the earliest signs of lesion development. 20 patients
      with definite relapsing-remitting multiple sclerosis were analysed with regard to
      cerebral blood volume, cerebral blood flow, mean transit time and apparent
      diffusion coefficient (ADC), as well as conventional MRI parameters, on monthly
      follow-up scans. Among 89 gadolinium-enhancing lesions, we selected 18 that
      developed during the study and met strict inclusion criteria. In these, changes
      of perfusion parameters were detectable not only prior to the BBB breakdown, but
      also prior to increases in the ADC. Our data indicate that inflammation is
      accompanied by altered local perfusion, which can be detected prior to
      permeability of the BBB.

PMID- 14570817
TI  - Encephalitis lethargica syndrome: 20 new cases and evidence of basal ganglia
      autoimmunity.
AB  - In 1916, von Economo first described encephalitis lethargica (EL), a CNS disorder
      presenting with pharyngitis followed by sleep disorder, basal ganglia signs
      (particularly parkinsonism) and neuropsychiatric sequelae. Since the 1916-1927
      epidemic, only sporadic cases have been described. Pathological studies revealed
      an encephalitis of the midbrain and basal ganglia, with lymphocyte (predominantly
      plasma cell) infiltration. The EL epidemic occurred during the same time period
      as the 1918 influenza pandemic, and the two outbreaks have been linked in the
      medical literature. However, von Economo and other contemporary scientists
      thought that the 1918 influenza virus was not the cause of EL. Recent examination
      of archived EL brain material has failed to demonstrate influenza RNA, adding to
      the evidence that EL was not an invasive influenza encephalitis. By contrast, the
      findings of intrathecal oligoclonal bands (OCB) and beneficial effects of steroid
      treatments have provoked the hypothesis that EL may be immune-mediated. We have
      recently seen 20 patients with a similar EL phenotype, 55% of whom had a
      preceding pharyngitis. The patients had remarkable similarity to the historical
      descriptions of EL: sleep disorder (somnolence, sleep inversion or insomnia),
      lethargy, parkinsonism, dyskinesias and neuropsychiatric symptoms. CSF
      examination commonly showed elevated protein and OCB (75 and 69% respectively).
      Investigation found no evidence of viral encephalitis or other recognized causes
      of rapid-onset parkinsonism. MRI of the brain was normal in 60% but showed
      inflammatory changes localized to the deep grey matter in 40% of patients. We
      investigated the possibility that this phenotype could be a postinfectious
      autoimmune CNS disorder, and therefore similar to Sydenham's chorea. Anti
      streptolysin-O titres were elevated in 65% of patients. Furthermore, western
      immunoblotting showed that 95% of EL patients had autoantibodies reactive against
      human basal ganglia antigens. These antibodies were also present in the CSF in
      four patients tested. By contrast, antibodies reactive against the basal ganglia
      were found in only 2-4% of child and adult controls (n = 173, P < 0.0001). Rather
      than showing polyspecific binding, these antibodies bound to common neural
      autoantigens of molecular weight 40, 45, 60 and 98 kDa. Regional tissue
      comparisons showed that the majority of these autoantigens were specific to or
      enriched in CNS tissue. Immunohistochemistry with secondary staining localized
      antibody binding to neurons rather than glial populations. Further investigation
      is required to determine whether these antibodies affect neuronal function (i.e.
      whether they are pathogenic anti-neuronal antibodies). Histopathology in one case
      demonstrated striatal encephalitis with perivenous B- and T-lymphocytic
      infiltration. We believe an EL-like syndrome is still prevalent, and propose that
      this syndrome may be secondary to autoimmunity against deep grey matter neurons.

PMID- 14570818
TI  - Novel presenilin 1 mutation with profound neurofibrillary pathology in an
      indigenous Southern African family with early-onset Alzheimer's disease.
AB  - Genetically determined Alzheimer's disease (AD) is virtually unknown in Africa.
      We report clinicopathological findings and a presenilin 1 (PS1) mutation
      associated with early-onset AD in a large Xhosa family from Southern Africa.
      Twelve individuals spanning four generations were affected, four of whom
      underwent clinical and psychometric evaluation. Their phenotype was characterized
      by memory impairment beginning in the early part of the fifth decade, with
      progressive dementing illness lasting 6-7 years that did not appear to be
      modified by the presence of an apolipoprotein E (APOE)-epsilon 4 allele. Initial
      linkage-based analysis using known DNA markers suggested allele cosegregation
      with a locus on chromosome 14. Direct sequencing of the PS1 gene disclosed a
      novel I143M (ATT to ATG at nucleotide 677) mutation that lies in a cluster in the
      second transmembrane domain of the protein. Examination of the proband's brain at
      autopsy revealed severe AD pathology characterized by neuronal loss, abundant
      beta amyloid (A beta) neuritic plaques (A beta 42) and neurofibrillary
      degeneration extending into the brainstem. The phenotype of the I143M mutation
      was clearly associated with a high degree of neurofibrillary change compared with
      early-onset sporadic AD cases. Although sporadic cases of AD do exist in African
      populations, our study confirms the existence of early-onset familial AD among
      indigenous Southern Africans.

PMID- 14570819
TI  - Does cerebrovascular disease affect the coupling between neuronal activity and
      local haemodynamics?
AB  - The relationship between neurophysiological and cerebrovascular-metabolic
      findings in patients affected by severe cerebrovascular deficits was investigated
      by comparing magnetoencephalographic (MEG-evoked fields) and blood oxygen level
      dependent functional MRI (BOLD fMRI) responses to median nerve electric
      stimulation. Despite the use of identical stimuli, the two techniques elicited
      always-detectable responses in the control group (10 subjects), but demonstrated
      uncorrelated activation properties in our patient sample (10 subjects). All
      patients showed clear MEG signals in both the affected and unaffected
      hemispheres, indicating well synchronized, stimulus-locked firing of neurons in
      the primary sensorimotor cortex, but some patients showed no fMRI activation in
      either the affected or the unaffected hemisphere. In order to clarify the origin
      of this uncoupling, we investigated the possible role of lesion site, white
      matter hyperintensities, current medication, risk factors, anatomy of the neck
      vessels, and cerebral vasomotor reactivity (VMR) as measured by transcranial
      Doppler (TCD) during CO2 inhalation. Neither neuronal activation properties nor
      any of the considered factors were related to the lack of fMRI activation, with
      the exception of altered vasomotor reactivity, which was, on the contrary,
      strongly related. Preserved VMR was paired with absent BOLD bilaterally in the
      only patient affected by microangiopathy. This finding suggests that BOLD
      contrast could be more sensitive than TCD to chronic microvascular impairments,
      measuring small- rather than large- vessel reactivity.

PMID- 14570820
TI  - MRI-based volumetric differentiation of sporadic cerebellar ataxia.
AB  - The term idiopathic cerebellar ataxia (IDCA) designates a variety of cerebellar
      syndromes that may present with a purely cerebellar syndrome (IDCA-C) or with
      additional extracerebellar features (IDCA-P). Multiple system atrophy is also a
      sporadic neurodegenerative disorder of unknown origin that may cause prominent
      cerebellar symptoms (MSA-C). The final neuropathological answer to the question
      whether IDCA-P and MSA-C represent different varieties of one disease or two
      distinct entities is still lacking. Three-dimensional MRI-based volumetry allows
      morphological investigations intra vitam. Volumetric analysis of cerebellum,
      brainstem and basal ganglia was therefore performed in 46 patients with sporadic
      cerebellar ataxia and 16 age-matched healthy controls. Patients with dementia
      were excluded from the study since cognitive impairment is an exclusion criterion
      for the diagnosis of MSA. Cerebellar patients were clinically divided into two
      groups: 33 patients with multiple system atrophy with prominent cerebellar
      symptoms (MSA-C) and 13 patients with extracerebellar features not corresponding
      to MSA-C (IDCA-P). There was evidence for substantial cerebellar atrophy in both
      cerebellar groups while additional brainstem atrophy was significantly more
      pronounced in MSA-C patients. Absolute caudate and putamen atrophy was found to
      be restricted to single MSA-C individuals while group comparisons of mean volumes
      did not yield significant differences from controls. Based on the volumetric
      data, diagnosis could be correctly predicted in 94% of control, 82% of MSA-C and
      100% of IDCA-P individuals. The finding of specific imaging characteristics
      strengthens (i) the value of MRI volumetry in separating MSA-C from other types
      of sporadic cerebellar ataxia, and (ii) the hypothesis of two independent
      neurodegenerative disorders in MSA-C and IDCA-P.

PMID- 14570821
TI  - The structural brain correlates of neurological soft signs in AESOP first-episode
      psychoses study.
AB  - Patients with schizophrenia and related psychoses have an excess of minor
      neurological abnormalities (neurological soft signs) of unclear neuropathological
      origin. These include poor motor coordination, sensory perceptual difficulties
      and difficulties in sequencing complex motor tasks. Neurological soft signs seem
      not to reflect primary tract or nuclear pathology. It still has to be established
      whether neurological soft signs result from specific or diffuse brain structural
      abnormalities. Studying their anatomical correlates can provide not only a better
      understanding of the aetiopathogenesis of soft signs, but also of the
      pathophysiology of schizophrenia. Surprisingly few studies have investigated the
      brain correlates of neurological soft signs. In the present study, we
      investigated the relationship between brain structure and neurological soft signs
      in an epidemiologically based sample of 77 first-episode psychosis patients. We
      used the Neurological Evaluation Scale for neurological assessment and high
      resolution MRI and voxel-based methods of image analysis to investigate brain
      structure. Higher rates of soft neurological signs (both motor and sensory) were
      associated with a reduction of grey matter volume of subcortical structures
      (putamen, globus pallidus and thalamus). Signs of sensory integration deficits
      were additionally associated with volume reduction in the cerebral cortex,
      including the precentral, superior and middle temporal, and lingual gyri.
      Neurological soft signs and their associated brain changes were independent of
      antipsychotic exposure. We conclude that neurological soft signs are associated
      with regional grey matter volume changes and that they may represent a clinical
      sign of the perturbed cortical-subcortical connectivity that putatively underlies
      psychotic disorders.

PMID- 14570822
TI  - How predictive is grip force control in the complete absence of somatosensory
      feedback?
AB  - Grip force control relies on accurate internal models of the dynamics of our
      motor system and the external objects we manipulate. Internal models are not
      fixed entities, but rather are trained and updated by sensory experience. Sensory
      feedback signals relevant object properties and mechanical events, e.g. at the
      skin-object interface, to modify motor commands and update internal
      representations automatically. Here we prove that intact sensory feedback is
      essential for predictive grip force regulation. The efficiency and precision of
      grip force adjustments to load fluctuations arising from vertical and horizontal
      point-to-point arm movements with a hand-held object were analysed in a
      chronically deafferented subject (G.L.) and three healthy control subjects. Point
      to-point movements started and ended with the object being held stationary. G.L.
      and healthy controls produced similar accelerations of the grasped object and
      consequently similar load magnitudes during vertical and horizontal movements.
      Compared with healthy controls, G.L. employed inefficiently high grip forces when
      holding and moving the object, indicating inaccurate force scaling to object
      weight and inertial loads. For healthy controls, the grip force profile was
      precisely timed to the movement-induced load fluctuations during vertical and
      horizontal movements. However, G.L.'s grip force profile was not processed to
      match differential loading requirements of movement direction. We conclude that
      predictive grip force control requires at least intermittent sensory feedback to
      signal the effectiveness of descending motor commands and to update internal
      models.

PMID- 14570823
TI  - Ca2+ channel blockers enhance neurotensin (NT) binding and inhibit NT-induced
      inositol phosphate formation in prostate cancer PC3 cells.
AB  - Neurotensin (NT) stimulates Ca2+ release and Ca2+ influx in many cells. Its
      contractile effects in smooth muscle are inhibited by removal of Ca2+ and by Ca2+
      channel blockers (CCBs). To better understand NT signaling in prostate cancer PC3
      cells, blockers of voltage-gated and store-operated Ca2+ channels (VGCC and SOCC)
      were tested for effects on NT-binding and signaling. Eight chemical types of
      agents, including VGCC-blocker nifedipine and SOCC-blocker SKF-96365 (1-[beta-[3
      (4-methoxyphenyl)-propoxy]-4-methoxyphenyl]-1H-imidazole), enhanced cellular NT
      binding up to 3-fold, while inhibiting (by congruent with 70%) NT-induced
      inositol phosphate (IP) formation. The ability to enhance NT binding correlated
      with the ability to inhibit NT-induced IP formation, and both effects were
      relatively specific for NT. Although cellular binding for beta2-adrenergic, V1a
      vasopressin, and epidermal growth factor receptors was not enhanced by these
      drugs, bombesin receptor binding was increased approximately equal to 19% and
      bombesin-induced IP formation was inhibited approximately equal to 15%. One
      difference was that the effect on NT binding was Ca2+-independent, whereas the
      effect on IP formation was Ca2+-dependent (in part). The Ca2+-dependent part of
      the IP response seemed to involve SOCC-mediated Ca2+ influx to activate
      phospholipase C (PLC)delta, while the Ca2+-independent part probably involved
      PLCbeta. Photoaffinity labeling of the NT receptor NTR1 was enhanced in CCB
      treated cells. NTR1 affinity was increased but NTR1 number and internalization
      were unchanged. Since CCBs did not alter NT binding to isolated cell membranes,
      the effects in live cells were indirect. These results suggest that CCBs exert
      two effects: 1) they inhibit NT-induced IP formation, perhaps by preventing Ca2+
      influx-dependent activation of PLCdelta; and 2) they enhance NTR1 affinity by an
      unexplained Ca2+-independent mechanism.

PMID- 14570824
TI  - Genetics of temporal lobe epilepsy.

PMID- 14570826
TI  - Multicentre European study of thalamic stimulation in essential tremor.

PMID- 14570825
TI  - Enteroviruses in chronic fatigue syndrome: "now you see them, now you don't".

PMID- 14570827
TI  - Molecular pathogenesis of neuroinflammation.
AB  - The past few years have seen significant progress towards understanding the
      mechanisms of immune surveillance and inflammation in the nervous system. In this
      review, the milestones of scientific discovery in this field are discussed, and
      the strengths and limitations of the different ways of examining the molecular
      pathogenesis of neuro-inflammation examined. The review is limited to the
      inflammatory reactions of the central nervous system that occur in multiple
      sclerosis and experimental autoimmune encephalomyelitis.

PMID- 14570828
TI  - Neuroimaging tools to rate regional atrophy, subcortical cerebrovascular disease,
      and regional cerebral blood flow and metabolism: consensus paper of the EADC.
AB  - Neuroimaging is a mainstay in the differential diagnosis of patients with
      cognitive impairment. The often equivocal clinical pictures, the prognostic
      uncertainty of the earliest stages of mild cognitive impairment, and the subtle
      brain changes mean that neuroimaging techniques are of potentially great
      incremental diagnostic value. A number of methods, ranging from very simple
      subjective visual ratings to highly sophisticated computerised tools, have been
      developed, which allow rating of structural and functional brain changes. The
      choice of the method is not obvious, and current guidelines provide no
      indications on which tools should be preferred. In this paper, we give
      indications for tools with demonstrated accuracy for detecting regional atrophy,
      cerebrovascular disease, and regional brain function, and discuss these according
      to increasing technological complexity, ranging from those with high feasibility
      that can be used at the patient's bedside to highly technological ones that
      require trained personnel and specific hardware and software.

PMID- 14570831
TI  - Multicentre European study of thalamic stimulation in essential tremor: a six
      year follow up.
AB  - BACKGROUND: Thalamic stimulation is an efficient treatment for disabling
      essential tremor, as previously shown, but follow up has mostly been short term.
      OBJECTIVES: To see whether good results can be maintained in the longer term.
      METHODS: 37 patients with essential tremor had implantation of a thalamic
      stimulator, either unilaterally or bilaterally. The results at one year have been
      reported earlier. After six years, 19 patients were available for follow up. The
      main instrument for evaluation was the essential tremor rating scale. The
      patients were examined with pulse generators turned on and off. RESULTS: In the
      majority of patients, the very good results with stimulation seen at one year
      were maintained after a mean of 6.5 years. The reduction in tremor scores and
      improvement in activities of daily living were highly significant compared with
      baseline and with the stimulation turned off. There were few serious adverse
      events. Minor side effects related to stimulation were common. Few device related
      complications were observed and most could be resolved. CONCLUSIONS: Good
      reduction in tremor can be maintained for more than six years in the majority of
      these severely disabled patients. Thalamic stimulation can be recommended in
      essential tremor where there is insufficient response to drug treatment. Surgical
      procedures and follow up should be concentrated in relatively few centres, which
      will thereby acquire a high degree of expertise.

PMID- 14570830
TI  - Enterovirus related metabolic myopathy: a postviral fatigue syndrome.
AB  - OBJECTIVE: To detect and characterise enterovirus RNA in skeletal muscle from
      patients with chronic fatigue syndrome (CFS) and to compare efficiency of muscle
      energy metabolism in enterovirus positive and negative CFS patients. METHODS:
      Quadriceps muscle biopsy samples from 48 patients with CFS were processed to
      detect enterovirus RNA by two stage, reverse transcription, nested polymerase
      chain reaction (RT-NPCR), using enterovirus group specific primer sets. Direct
      nucleotide sequencing of PCR products was used to characterise the enterovirus.
      Controls were 29 subjects with normal muscles. On the day of biopsy, each CFS
      patient undertook a subanaerobic threshold exercise test (SATET). Venous plasma
      lactate was measured immediately before and after exercise, and 30 minutes after
      testing. An abnormal lactate response to exercise (SATET+) was defined as an
      exercise test in which plasma lactate exceeded the upper 99% confidence limits
      for normal sedentary controls at two or more time points. RESULTS: Muscle biopsy
      samples from 20.8% of the CFS patients were positive for enterovirus sequences by
      RT-NPCR, while all the 29 control samples were negative; 58.3% of the CFS
      patients had a SATET+ response. Nine of the 10 enterovirus positive cases were
      among the 28 SATET+ patients (32.1%), compared with only one (5%) of the 20 SATET
      patients. PCR products were most closely related to coxsackie B virus.
      CONCLUSIONS: There is an association between abnormal lactate response to
      exercise, reflecting impaired muscle energy metabolism, and the presence of
      enterovirus sequences in muscle in a proportion of CFS patients.

PMID- 14570832
TI  - Chronic deep brain stimulation for the treatment of tremor in multiple sclerosis:
      review and case reports.
AB  - BACKGROUND: Deep brain stimulation (DBS) offers a non-ablative alternative to
      thalamotomy for the surgical treatment of medically refractory tremor in multiple
      sclerosis. However, relatively few outcomes have been reported. OBJECTIVE: To
      provide a systematic review of the published cases of DBS use in multiple
      sclerosis and to present four additional patients. METHODS: Quantitative and
      qualitative review of the published reports and description of a case series from
      one centre. RESULTS: In the majority of reported cases (n=75), the surgical
      target for DBS implantation was the ventrointeromedial nucleus of the thalamus.
      Tremor reduction and improvement in daily functioning were achieved in most
      patients, with 87.7% experiencing at least some sustained improvement in tremor
      control postsurgery. Effects on daily functioning were less consistently assessed
      across studies; in papers reporting relevant data, 76.0% of patients experienced
      improvement in daily functioning. Adverse effects were similar to those reported
      for DBS in other patient populations. CONCLUSIONS: Few of the studies reviewed
      used highly standardised quantitative outcome measures, and follow up periods
      were generally one year or less. Nonetheless, the data suggest that chronic DBS
      often produces improved tremor control in multiple sclerosis. Complete cessation
      of tremor is not necessarily achieved, there are cases in which tremor control
      decreases over time, and frequent reprogramming appears to be necessary.

PMID- 14570833
TI  - A study of stereotypic behaviours in Alzheimer's disease and frontal and temporal
      variant frontotemporal dementia.
AB  - OBJECTIVE: To document the prevalence and pattern of stereotypic behaviour in
      patients with Alzheimer's dementia and frontal and temporal variants of
      frontotemporal dementia. Secondly, to examine the relationship between
      stereotypic and other neuropsychiatric behaviours. METHODS: Patients with the
      following were studied; Alzheimer's disease (n=28), frontal variant
      frontotemporal dementia (fvFTD, n=18), and semantic dementia-the temporal lobe
      variant of FTD (n=13). All patients were assessed using the Neuropsychiatric
      Inventory (NPI), the Mini-Mental State Examination, Addenbrooke's Cognitive
      Examination, and the Clinical Dementia Rating scale. Patients were also rated on
      the newly devised Stereotypic and Ritualistic Behaviour (SRB) subscale, which was
      designed as an addendum to the NPI. RESULTS: There was no significant difference
      across diagnostic groups in terms of age, sex, or severity of cognitive deficits.
      The overall NPI was significantly higher in patients with fvFTD compared with the
      other two groups, but fvFTD and semantic dementia showed a similar, and
      significantly increased, prevalence of stereotypic behaviours on the SRB
      subscale. Within the FTD group as a whole these behaviours were more likely to be
      complex, whereas in Alzheimer's disease, when present, such behaviours tended to
      be more simple stereotypies or stimulus bound repetitive behaviours. Stereotypic
      behaviours were not correlated with either disease severity or the extent of
      cognitive impairment in the fvFTD group, but were in the other two diagnostic
      groups. CONCLUSION: Complex stereotypic behaviours are a core feature of the
      dementing syndrome in FTD and may reflect early and specific deficits in
      orbitofrontal circuitry and basal ganglia involvement.

PMID- 14570834
TI  - Vestibulo-ocular arreflexia in families with spinocerebellar ataxia type 3
      (Machado-Joseph disease).
AB  - OBJECTIVE: To identify the presence of vestibulo-ocular arreflexia in patients
      with Machado-Joseph disease (MJD), which can easily be diagnosed at the bedside.
      METHODS: Seven patients with MJD from five unrelated families and 11 patients
      with sporadic or hereditary cerebellar ataxia other than MJD underwent a detailed
      neuro-otological and oculomotor examination. Six MJD and five non-MJD patients
      also underwent electro-oculographic recordings and caloric tests. RESULTS: Gaze
      evoked nystagmus, smooth pursuit, and saccade abnormalities were found in both
      MJD and non-MJD patients. However, in all seven MJD patients but in none of the
      non-MJD patients, sudden passively induced head thrust to both sides elicited
      pathological corrective catch-up saccades, indicating bilateral loss of the
      horizontal vestibulo-ocular reflex. This was further confirmed in six MJD
      patients who had absent vestibular response to both a standard caloric test and
      ice water ear irrigation. Nystagmus was induced by standard caloric irrigation in
      all non-MJD patients examined. There was no correlation between the loss of
      vestibular function and the severity of cerebellar impairment. CONCLUSIONS: The
      presence of vestibulo-ocular arreflexia, as measured by the head thrust test in a
      patient with dominant cerebellar ataxia, strongly suggests the diagnosis of MJD.

PMID- 14570835
TI  - Age and duration related changes in muscle sympathetic nerve activity in
      Parkinson's disease.
AB  - OBJECTIVE: To clarify the characteristics of sympathetic vasomotor function in
      Parkinson's disease by sympathetic neurographic analysis. METHODS: Muscle
      sympathetic nerve activity (MSNA) was recorded using a microneurographic
      technique at rest and during head up tilt in 18 patients with idiopathic
      Parkinson's disease and 21 healthy controls. RESULTS: Heart rate and blood
      pressure at rest did not differ between index and control subjects. The increase
      in these variables and MSNA in response to tilting was slightly blunted in the
      Parkinson's group. Resting MSNA showed a negative correlation with age in
      patients with Parkinson's disease (p<0.05) and a positive correlation with age in
      controls (p<0.01). There was a negative correlation between duration of disease
      or disability levels and MSNA (p<0.01). CONCLUSIONS: Sympathetic vasomotor
      function may be related to age and disease duration in Parkinson's disease.

PMID- 14570836
TI  - Early cognitive decline in Creutzfeldt-Jakob disease associated with human growth
      hormone treatment.
AB  - BACKGROUND: Most cases of Creutzfeldt-Jakob disease (CJD) in recipients of human
      cadaveric growth hormone present with a cerebellar syndrome. Dementia is thought
      to occur late and as a minor feature of the illness. However, neuropsychology
      data published on these cases are largely qualitative and anecdotal. The first
      published case does include a neuropsychological assessment seven months after
      the onset of a cerebellar syndrome, showing evidence of intellectual decline.
      Subsequent reports hint that cognitive problems may be present in the initial
      stages of the illness. OBJECTIVE: To assess early cognition in Creutzfeldt-Jakob
      disease in recipients of pituitary derived human growth hormone. METHODS:
      Detailed neuropsychology assessment is reported at referral (mean 4.5 months from
      the onset of symptoms; range 4 to 6 months) in five patients with histologically
      proven human growth hormone derived CJD. RESULTS: All cases presented with a
      cerebellar syndrome and only one had noticed mild memory problems. On formal
      testing, however, four had demonstrable mild intellectual decline, as measured on
      the WAIS-R. One case showed selective visual memory impairment and frontal
      executive dysfunction. CONCLUSIONS: These findings suggest that, although not the
      presenting feature, mild cognitive decline may be evident in the early stages of
      CJD associated with human cadaveric growth hormone treatment.

PMID- 14570838
TI  - "Bottom-up" and "top-down" effects on reading saccades: a case study.
AB  - OBJECTIVE: To investigate the role right foveal/parafoveal sparing plays in
      reading single words, word arrays, and eye movement patterns in a single case
      with an incongruous hemianopia. METHODS: The patient, a 48-year-old right handed
      male with a macular sparing hemianopia in his left eye and a macular splitting
      hemianopia in his right eye, performed various reading tasks. Single word reading
      speeds were monitored using a "voice-trigger" system. Eye movements were recorded
      while reading three passages of text, and PET data were gathered while the
      subject performed a variety of reading tasks in the camera. RESULTS: The patient
      was faster at reading single words and text with his left eye compared with his
      right. A small word length effect was present in his right eye but not his left.
      His eye movement patterns were more orderly when reading text with his left eye,
      making fewer saccades. The PET data provided evidence of "top-down" processes
      involved in reading. Binocular single word reading produced activity in the
      representation of foveal V1 bilaterally; however, text reading with the left eye
      only was associated with activation in left but not right parafoveal V1, despite
      there being visual stimuli in both visual fields. CONCLUSIONS: The presence of a
      word length effect (typically associated with pure alexia) can be caused by a
      macular splitting hemianopia. Right parafoveal vision is not critically involved
      in single word identification, but is when planning left to right reading
      saccades. The influence of top-down attentional processes during text reading can
      be visualised in parafoveal V1 using PET.

PMID- 14570837
TI  - Incidence of endemic ataxic polyneuropathy and its relation to exposure to
      cyanide in a Nigerian community.
AB  - BACKGROUND: The occurrence of ataxic polyneuropathy in an endemic area in south
      west Nigeria has been attributed to exposure to cyanide from cassava foods.
      However, it has been shown that the prevalence of ataxic polyneuropathy is not
      high in several communities in the tropics where exposure to cyanide from cassava
      foods is high. OBJECTIVES: To determine the incidence of ataxic polyneuropathy in
      an endemic community, and to compare the intake of cassava foods, exposure to
      cyanide, and levels of thiols in cases and controls. METHODS: A cohort of 3167
      healthy subjects aged 10 years and over in Ososa, Nigeria, was followed for two
      years, screened, and examined neurologically. Ataxic polyneuropathy was diagnosed
      if sensory polyneuropathy and sensory gait ataxia were both present. Controls
      were selected randomly within 10 year age groups of subjects who screened
      negative. Intake of cassava foods, exposure to cyanide, concentrations of thiols
      (glutathione, cysteine, and gamma glutamylcysteine) in plasma, and visual evoked
      potentials were measured. RESULTS: Person-years of follow up were 6246 for 1469
      male and 1698 female subjects in the cohort. The incidence of ataxic
      polyneuropathy was 64 per 10,000 person-years (31 for male and 93 for female
      subjects). Multivariate odd ratios were 0.78 (95% CI 0.23 to 2.61) for intake of
      the commonest cassava food, and 1.64 (0.56 to 5.09) for concentration of
      thiocyanate in plasma. The concentration of thiols was less than the reference
      limits in two controls, but in none of the cases. The latency of P100 was
      prolonged in 20 cases (69%) compared with 14 controls (42%) (p<0.05).
      CONCLUSIONS: The incidence of ataxic polyneuropathy is high in Ososa, Nigeria,
      but the intake of cassava foods, exposure to cyanide, and levels of thiols, are
      not related to the occurrence. These findings do not suggest that cyanide is the
      cause of endemic ataxic polyneuropathy.

PMID- 14570839
TI  - Placing nasogastric tubes in stroke patients with dysphagia: efficiency and
      tolerability of the reflex placement.
AB  - Temporary dysphagia affects up to 50% of stroke patients in the acute stage of
      their illness and often necessitates tube feeding. In these patients, the placing
      of nasogastric tubes is often difficult or impossible. This study evaluated the
      efficiency and tolerability of a previously described new method for tube
      placing, which utilises the induction of the swallowing reflex and has therefore
      been called "reflex placement". In 14 of 16 patients in whom the conventional
      approach failed, the new method was successful. A comparison of the
      cardiovascular responses to both methods in another 12 patients revealed
      significantly smaller increases in heart rate and systolic blood pressure during
      application of the new method. We therefore suggest the use of reflex placement
      in patients who have suffered a stroke and need tube feeding due to dysphagia.

PMID- 14570840
TI  - Intracranial aneurysm: seen and unseen.

PMID- 14570841
TI  - Brain lesions in the course of generalised tetanus.
AB  - A 47-year-old woman developed left hemiparesis primarily affecting the lower
      limbs during the course of severe generalised tetanus. MRI on the 82nd hospital
      day revealed cortical and subcortical lesions predominantly in the right frontal
      and parietal lobes in addition to marked brain atrophy. Three months later, the
      enhancing lesions were still present on follow up MRI. We postulate that
      structures above brainstem may be involved in severe generalised tetanus.

PMID- 14570842
TI  - Olfactory dysfunction in degenerative ataxias.
AB  - Several lines of evidence suggest that the cerebellum may play a role in higher
      order olfactory processing. In this study, we administered the University of
      Pennsylvania Smell Identification Test (UPSIT), a standardised test of olfactory
      function, to patients with ataxias primarily due to cerebellar pathology
      (spinocerebellar ataxias and related disorders) and to patients with Friedreich
      ataxia, an ataxia associated mainly with loss of afferent cerebellar pathways.
      UPSIT scores were slightly lower in both patient groups than in the control
      subjects, but no differences were noted between the scores of the Friedreich and
      the other ataxia patients. Within the Friedreich ataxia group, the smell test
      scores did not correlate with the number of pathologic GAA repeats (a marker of
      genetic severity), disease duration, or categorical ambulatory ability. UPSIT
      scores did not correlate with disease duration, although they correlated
      marginally with ambulatory status in the patients with cerebellar pathology. This
      study suggests that olfactory dysfunction may be a subtle clinical component of
      degenerative ataxias, in concordance with the hypothesis that the cerebellum or
      its afferents plays some role in central olfactory processing.

PMID- 14570843
TI  - Spinal dural arteriovenous fistulas: clinical features in 80 patients.
AB  - The aim of this study was to describe the clinical spectrum of spinal dural
      arteriovenous fistulas (SDAF) in a large group of patients. We studied the
      records of 80 patients who were diagnosed with an SDAF in six hospitals over a 15
      year period (1985-2001). We extracted data on demographic variables, initial
      symptoms, symptoms at the time of diagnosis, level of SDAF, and medical history.
      Most patients were middle aged men, and most SDAF were located in the midthoracic
      region. The median time to diagnosis of 80 patients with an SDAF was 15 months
      (range 7 days-197 months). The most common initial symptoms were gait
      disturbances (34%), numbness (24%), and paresthesias (21%). At the time of
      diagnosis, most common symptoms were micturition problems (80%), leg weakness
      (78%), and numbness in the legs or buttocks (69%). The combination of all three
      symptoms was present in 58% of patients. Any symptoms or signs related to sacral
      segments had developed in 67 patients (84%). Fifteen patients (19%) had become
      wheelchair bound. SDAF is difficult to diagnose, and the delay between first
      symptoms and treatment is often long. In middle aged men who present with
      disturbances of gait with ascending motor and sensory deficits, and who
      subsequently report impaired voiding or other sphincter disturbance, SDAF is one
      of the first diagnoses that should spring to mind.

PMID- 14570845
TI  - Sir Thomas Clifford Allbutt.

PMID- 14570844
TI  - Apolipoprotein E genotypes and outcome from out of hospital cardiac arrest.
AB  - Genetic factors may influence outcome from cardiac arrest. In Seattle, WA,
      paramedics collected blood specimens from patients who had suffered cardiac
      arrest outside of a medical institution (out of hospital cardiac arrest). We
      examined associations between apolipoprotein E (APOE) genotype and outcome in 134
      who died "in the field", 131 who died in the hospital, 198 patients who were
      discharged from hospital alive, and 64 control subjects. APOE genotype was not
      significantly related to outcome, including being alive at and being independent
      by 3 months after the arrest. Specifically, having one or two alleles of APOE
      epsilon4 or having APOE epsilon3/epsilon3 was not related to outcome, even after
      controlling for age, sex, race, and initial rhythm. We failed to confirm previous
      studies and found no significant associations between APOE genotype and outcome
      from out of hospital cardiac arrest.

PMID- 14570846
TI  - Task specific focal dystonia: a presentation of spinocerebellar ataxia type 6.

PMID- 14570847
TI  - Identification of amoebae in the CSF in a patient with meningoencephalitis.

PMID- 14570848
TI  - Bilateral cerebellar ataxia as the sole manifestation of a unilateral rostral
      pontine tegmental infarct.

PMID- 14570850
TI  - The harsh realities facing the use of SPECT imaging in monitoring disease
      progression in Parkinson's disease.

PMID- 14570851
TI  - A forum for commentaries on recent publications. FIRKO mouse report: important
      new model--but questionable interpretation.

PMID- 14570852
TI  - Increased expression of the Huntingtin interacting protein-1 gene in cells from
      Hutchinson Gilford Syndrome (Progeria) patients and aged donors.
AB  - Hutchinson Gilford syndrome (progeria [PG]) is a human disease associated with
      accelerated aging. To elucidate the acceleration mechanism, we first tried to
      transform a PG-derived cell line by infection of a recombinant adenovirus
      expressing HPV (human papilloma virus)-E6 and HPV-E7 genes. The transfected PG
      cells had a greater number of population doublings (PD) (>80), faster doubling
      time, and less staining of senescence-associated ss-galactosidase than the
      nontransfected PG cells. The transfected cells also showed markedly more
      detectable telomerase activity than the nontransformed cells. The expression
      levels of the genes in the E6-transduced and E7-transduced cell line were then
      compared with those of the nontransfected cell line using an mRNA differential
      display method, following reverse-transcriptase polymerase chain reaction
      analysis. Expression of huntingtin interacting protein-1 (HIP-1) gene was found
      to be increased not only in PG cells but also in fibroblast cells from aged
      healthy donors. Thus, HIP-1 might be a molecular assistant in the pathogenesis of
      the cellular senescent process in the human cells tested.

PMID- 14570853
TI  - Relationship between aging and renal high-affinity sodium-dependent dicarboxylate
      cotransporter-3 expression characterized with antifusion protein antibody.
AB  - Sodium-dependent dicarboxylate cotransporter (NaDC), which is responsible for the
      transportation of intermediates of the Krebs cycle, has been implicated in
      extending the life span of drosophila. In the present study, we cloned an
      intracellular domain segment of human kidney NaDC-3, which is 75% identical to
      that of the rat, constructed a polyclonal antibody against fusion protein of
      glutathione S-transferase (GST)-NaDC-3, and detected its renal expression changes
      with aging in both Wistar rats and normal humans. Western blot and
      immunohistochemistry confirmed the specificity of the antibody, and its location
      was found to be on the basolateral membrane of the renal proximal tubule. In
      addition, Western and Northern blots showed that NaDC-3 in kidneys significantly
      increased with age in Wistar rats. In healthy humans, renal NaDC-3 abundance also
      increased with age. Our results demonstrated that NaDC-3 expression was increased
      in aged Wistar rats and aged people, indicating that NaDC-3 may have a role in
      the process of kidney aging.

PMID- 14570854
TI  - Differential effectiveness of low-intensity exercise in young and old rats.
AB  - Low-intensity exercise increases strength and function in old adults, but it is
      unclear if change occurs secondary to "neural adaptation" or to intrinsic muscle
      adaptation. Whether function and strength change concomitantly is also unclear.
      We examined effects of a modest intensity, 10-session exercise program on muscle
      mass, contractile force, and function (gait) in 6-month-old and 30-month-old
      rats. Animals underwent 45 minutes of activity (e.g., ramp walking, balancing) 5
      days/week. In old animals, a significant increase in muscle mass and peak
      contractile force occurred with exercise in soleus, plantaris, extensor digitorum
      longus, and peroneus longus compared with controls, but did not restore values to
      those for young controls. The increase in muscle force in old rats was
      accompanied by a significant lengthening of stride (90 +/- 9 to 103 +/- 15 mm),
      which was still 23% less than stride values for young rats. Changes in muscle
      function and gait with exercise were not apparent in young rats. Results suggest
      that (a). rapid and significant changes in muscle mass and strength in an aged
      organism can occur with a modest activity program, (b). the threshold for muscle
      adaptation may differ in young versus old rats, and (c). changes in strength and
      function in old rats may occur concomitantly.

PMID- 14570855
TI  - Effect of age on peripheral vascular response to transverse aortic banding in
      mice.
AB  - The placement of a ligature to constrict the transverse aorta has become a
      standard procedure to induce cardiac hypertrophy in mice. Apart from cardiac
      response, there are adaptive changes in the proximal and distal arterial system
      that function to maintain adequate peripheral perfusion. The purpose of this
      study was to characterize the peripheral vascular response by measuring the
      carotid blood flow using noninvasive Doppler methods, and to investigate the
      effect of aging on the adequacy and timing of the response after aortic banding
      in mice. Five 16-month-old and 9 4-month-old male B6D2F1 mice underwent
      transverse aortic banding. Blood flow velocity was measured with Doppler in the
      right and left carotid arteries (RCA and LCA) before, 1 day after, and 7 days
      after, banding. Pulsatility index defined as (peak - minimum)/mean velocity was
      used to estimate local compliance and distal arterial resistance. The RCA/LCA
      mean velocity ratio was lower and pulsatility index ratio was higher at 1 day
      after banding in older mice. However, at 7 days, the RCA/LCA mean velocity ratio
      and pulsatility index ratio were similar between the 2 age groups. Our data
      indicate that there is an age-related delay in the development of vascular
      adaptations in carotid arteries after aortic banding. Older mice take a longer
      time for adaptation to establish adequate and equal mean flow velocity in the
      carotid arteries.

PMID- 14570856
TI  - Mineralocorticoid receptor-mediated inhibition of the hypothalamic-pituitary
      adrenal axis in aged humans.
AB  - In aged humans, diminished mineralocorticoid receptor (MR)-mediated feedback in
      the brain could contribute to impaired feedback regulation of the hypothalamic
      pituitary-adrenal (HPA) axis, but no study specifically compared young and old
      individuals with regard to MR function. We examined 10 healthy young (mean age +/
      SD [standard deviation] 26.1 +/- 2.9 years) and 10 elderly men (68.3 +/- 4.7
      years) at the nadir of cortisol levels (2:00 pm-9:00 pm) when HPA activity is
      mainly controlled by the MR. After pretreatment with 3 g metyrapone to minimize
      the impact of basal endogenous cortisol secretion, participants received orally,
      in randomized order on two separate occasions, either 0.5 mg of the MR agonist
      fludrocortisone or placebo. Fludrocortisone significantly decreased maximum
      adrenocorticotropic hormone (ACTH) and cortisol concentrations in both groups.
      ACTH and cortisol values after fludrocortisone were significantly higher in older
      men compared with young men. Our results implicate that a decrease in MR-mediated
      negative feedback contributes to the diminished feedback activity in older
      humans.

PMID- 14570858
TI  - Sarcopenia: causes, consequences, and preventions.
AB  - With the onset of advancing age, muscle tissue is gradually lost, resulting in
      diminished mass and strength, a condition referred to as sarcopenia. The sequela
      of sarcopenia often contributes to frailty, decreased independence, and
      subsequently increased health care costs. The following was adapted from an
      introduction to the conference "Sarcopenia, Age-Related Muscle Loss-Causes,
      Consequences, and Prevention," sponsored by the Kronos Longevity Research
      Institute in June 2002. This brief review will introduce potential mechanisms
      that may contribute to sarcopenia, although no one mechanism has yet, and may not
      completely, define this process. The only agreed-upon intervention from these
      proceedings was regular physical exercise, stressing weight-training for elderly
      men and women. However, even those individuals who maintain their fitness through
      exercise do not appear to be immune to sarcopenia.

PMID- 14570859
TI  - Exercise, aging, and muscle protein metabolism.
AB  - Age-associated alterations in muscle protein quantity and quality that adversely
      affect muscle structure, composition, and function have been referred to as
      sarcopenia. Muscle protein is metabolically active, and the age-associated loss
      of muscle protein mass is related to a loss of physical function and an inability
      to perform activities of daily living (physical frailty). It is important to
      maintain adequate reserves of muscle protein and amino acids as we age. As in all
      cachectic conditions, sarcopenia can be explained by an imbalance between the
      rates of muscle protein synthesis and muscle proteolysis, in which net muscle
      protein balance is negative. This review summarizes evidence that supports the
      notion that: (a). advancing age and physical frailty are associated with a
      reduction in the fasting rate of mixed and myosin heavy chain protein synthesis,
      which contributes to muscle protein wasting in advancing age; (b). this
      impairment can be corrected because resistance exercise acutely and dramatically
      increases the rate of muscle protein synthesis in men and women aged 76 years and
      older; and (c). resistance exercise training maintains a modest increment in the
      rate of muscle protein synthesis and contributes to muscle hypertrophy and
      improved muscle strength in frail elderly men and women. The cellular mechanisms
      responsible for these adaptations, as well as the role of nutrition and hormone
      replacement in reversing sarcopenia, require further investigation.

PMID- 14570860
TI  - Mechanisms and strategies to counter muscle atrophy.
AB  - Skeletal muscle size is modulated by a number of factors, including muscle load,
      utilization, and regenerative capacity. Surprisingly, actions that can promote
      muscle growth do not necessarily prevent the loss of muscle mass, or atrophy.
      This suggests that divergent mechanisms are important for the maintenance of
      muscle mass in different contexts. In acute atrophy, muscles rapidly lose mass
      when load is lacking, and this response seems to involve active elimination of
      myonuclei. In contrast, chronic atrophy, such as loss of muscle mass related to
      aging, is associated with impairments in muscle repair. In this review, two
      contexts in which muscle mass is lost are explored to determine if similar
      processes are involved.

PMID- 14570861
TI  - Treatment of unstable angina pectoris/non-ST-segment elevation myocardial
      infarction in elderly patients.
AB  - Elderly patients with unstable angina pectoris/non-ST-segment elevation
      myocardial infarction should be hospitalized. Precipitating factors should be
      identified and corrected. Electrocardiogram monitoring is important. Aspirin
      should be given as soon as possible and continued indefinitely. Clopidogrel
      should given for up to 9 months in patients in whom an early noninterventional
      approach is planned or in whom a percutaneous coronary intervention (PCI) is
      planned. Clopidogrel should be withheld for 5-7 days in patients in whom elective
      coronary artery bypass graft surgery (CABGS) is planned. A platelet glycoprotein
      IIb/IIIa inhibitor should also be given in addition to aspirin, clopidogrel, and
      heparin in patients in whom cardiac catheterization and PCI are planned. Patients
      whose symptoms are not fully relieved with three 0.4-mg sublingual nitroglycerin
      tablets or spray taken 5 minutes apart and the initiation of an intravenous beta
      blocker should be treated with continuous intravenous nitroglycerin. Beta
      blockers and angiotensin-converting enzyme (ACE) inhibitors should be given and
      continued indefinitely. The benefit of long-acting nondihydropyridine calcium
      channel blockers is limited to symptom control. Intra-aortic balloon pump
      counterpulsation should be used for severe ischemia that is continuing or occurs
      frequently despite intensive medical therapy or for hemodynamic instability.
      Statins should be used if the serum low-density lipoprotein (LDL) cholesterol is
      >or=100 mg/dl and continued indefinitely. Enoxaparin is preferable to intravenous
      unfractionated heparin in the absence of renal failure and unless CABGS is
      planned within 24 hours. Thrombolysis is not beneficial. High-risk patients
      should have an early invasive strategy with CABGS or PCI performed depending on
      the coronary artery anatomy, left ventricular function, presence or absence of
      diabetes, and findings on noninvasive testing. Following hospital discharge,
      patients should have intensive risk factor modification with cessation of
      smoking, maintenance of blood pressure below 135/85 mmHg, indefinite use of
      statins if needed to maintain the serum LDL cholesterol <100 mg/dl, intensive
      control of diabetes, maintenance of optimal weight, and daily exercise. Patients
      should be treated indefinitely with aspirin, beta blockers, and ACE inhibitors
      and with clopidogrel for up to 9 months. Nitrates should be given for ischemic
      symptoms. Hormonal therapy should not be given to postmenopausal women.

PMID- 14570862
TI  - Lower extremity physical performance and hip bone mineral density in elderly
      black and white men and women: cross-sectional associations in the Health ABC
      Study.
AB  - BACKGROUND: Aging is characterized by declines in physical capacity and bone
      mineral density (BMD), both of which contribute to increased risk for fracture.
      However, it is unclear if these factors coexist or are independent in elderly
      people, and if a relationship does exist, whether it varies by sex and/or race.
      METHODS: Data are from 847 white women, 723 black women, 927 white men, and 544
      black men aged 70-79 years participating in the Health Aging and Body Composition
      (ABC) Study, a cohort of well-functioning community-dwelling elders. BMD
      (g/cm(2)) of the hip (femoral neck and trochanter) was determined by dual X-ray
      absorptiometry. Physical capacity measures included knee extensor strength,
      repeated chair-stands, gait speed (6 m), walking endurance (400 m), and standing
      balance. RESULTS: In analyses of BMD as a continuous measure, BMD and physical
      performance were most consistently related at the trochanter in black women, even
      after adjusting for body size and several covariates including physical activity.
      For each performance measure, black women in the bottom quartile(s) had lower BMD
      than those in the top quartile(s). For the femoral neck, there was a significant
      association with performance tasks, except for the 400-m walk. In comparison,
      only chair-rise performance was related to BMD at the femoral neck, and knee
      extensor strength, chair-rise performance, and balance with the trochanter in
      white women. For white and black men, trends existed only for lower BMD in those
      with poorer knee extensor strength. CONCLUSIONS: In this cohort of well
      functioning young-old seniors, physical capacity is only modestly related to BMD
      at the hip. The association was strongest in black women, who as a group
      exhibited the poorest functional capacity in the cohort. Our data show that,
      although both poorer physical performance and low BMD are risk factors for
      fracture, they remain largely independent in the well-functioning young-old,
      except in black women. This independence suggests that interventions to reduce
      fracture incidence should be targeted at improving both physical performance and
      bone density.

PMID- 14570863
TI  - The development of fear of falling among community-living older women:
      predisposing factors and subsequent fall events.
AB  - BACKGROUND: Fear of falling is a common and potentially modifiable health problem
      among older persons. However, relatively little is known about who develops fear
      of falling or why. METHODS: From a representative cohort of community-living
      persons aged 72 years or older, we evaluated 313 women who had no fear of
      falling. These participants underwent a comprehensive in-home assessment and were
      reassessed for fear of falling 1 year later. Fall events were ascertained monthly
      using a validated fall calendar. RESULTS: 84 (27%) participants developed fear of
      falling at 1 year and 77 (25%) participants experienced at least one fall event.
      The predisposing factors for developing fear of falling included age 80 years or
      older (adjusted relative risk 1.48; 95% confidence intervals 1.04-2.12), visual
      impairment (1.42; 1.01-2.00), a sedentary lifestyle (1.96; 1.35-2.84), and no
      available emotional support (2.64; 1.57-4.41). The occurrence of a subsequent
      fall event was also significantly associated with developing fear of falling
      (unadjusted relative risk 1.70; 1.18-2.45), although this effect was observed
      only among participants who had at least one predisposing factor. CONCLUSIONS:
      Among community-living older women, fear of falling develops due to a combination
      of predisposing factors and subsequent fall events. Since many of the
      predisposing factors are related to fall risk, preventive efforts to reduce fear
      of falling may also decrease the likelihood of falling.

PMID- 14570864
TI  - Factors related to patient satisfaction with complete denture therapy.
AB  - BACKGROUND: Except for denture quality, many other factors are related to a
      patient's satisfaction with complete dentures (CDs). METHODS: A total of 222
      patients with CDs took a part in this study. A questionnaire divided into 3 parts
      was completed by both the patients and the dentist, independently. The patients
      rated their dentures using a scale ranging from 1 to 5 (1 = dissatisfaction to 5
      = excellent), and a dentist rated the quality of the denture and the denture
      bearing area. RESULTS: Patients were mostly satisfied with the quality of their
      CDs. Only 7.2% of the patients were absolutely not satisfied with their dentures.
      Patients with a low level of education were more satisfied in general with their
      aesthetic appearance. Patients with better self-perception of their affective
      status and quality of life showed higher levels of general satisfaction. Patients
      with better self-perception of their economic status showed lower levels of
      satisfaction. Younger patients wearing dentures for the first time, with short
      periods of being edentulous, and with better quality maxillary denture-bearing
      areas were more satisfied with the retention of maxillary CDs. In contrast,
      younger patients with first-time dentures, a short period of being edentulous,
      and with better quality mandibular denture-bearing areas gave lower ratings to
      the retention and comfort of wearing mandibular dentures. CONCLUSIONS: Level of
      education, self-perception of affective and economic status, and quality of life
      are all related to patient satisfaction. However, the quality of dentures shows
      the strongest correlation with patient satisfaction. Not only the quality of the
      denture-bearing area but the denture-wearing experience itself seems to be more
      important in determining patient satisfaction with mandibular CDs.

PMID- 14570865
TI  - Is social integration associated with the risk of falling in older community
      dwelling women?
AB  - BACKGROUND: Social integration may lead to social support and influence that may
      in turn protect older community-dwelling adults from falls. METHODS: We examined
      incident falls over 3 years across quartiles of social integration scores in 6692
      Caucasian women enrolled in the Study of Osteoporotic Fractures (mean age = 77 +/
      5 years). Social integration was assessed using family networks, friendship
      networks, and interdependence scores. Higher scores correspond to greater
      integration. Data were analyzed using Poisson regression with generalized
      estimating equations. Multivariate analyses were used to adjust for other risk
      factors and potential confounders. RESULTS: Women reported 11863 falls, averaging
      0.60 falls per person annually, 95% confidence interval (CI) (0.57, 0.63), or 600
      falls per 1000 women. In age-adjusted analysis, the average incidence rate of
      falls correlated inversely with family networks, interdependence, and composite
      integration scores (p <.05). In multivariate analysis, increasing family networks
      were inversely associated with fall risk, p(trend) =.02. Compared to the lowest
      quartile, the relative risk of falls (95% CI) associated with family network
      scores in the second, third, and fourth quartiles were 0.90 (0.79-1.03), 0.86
      (0.74-1.00), and 0.84 (0.71-0.99), respectively. CONCLUSIONS: Strong family
      networks may protect against the risk of falls in older community-dwelling
      adults.

PMID- 14570866
TI  - Serum insulin concentrations in daily drinkers compared with abstainers in the
      New Mexico elder health survey.
AB  - BACKGROUND: Recent epidemiological studies have shown that individuals who ingest
      alcohol regularly have a lower prevalence of diabetes mellitus than those who
      abstain. The purpose of this study was to compare serum glucose and insulin
      concentrations between daily drinkers and abstainers stratified by diabetic
      status (participants with diabetes, impaired glucose tolerance, and normal
      glucose tolerance) to determine if there was a difference in glucose sensitivity
      (resistance) that might explain the lower prevalence of diabetes in drinkers.
      METHODS: A cross-sectional community survey was conducted of 883 randomly
      selected Hispanic and non-Hispanic white men and women, aged >or=65 years,
      undergoing a home interview and 4-hour interview/examination in a senior health
      clinic (The New Mexico Elder Health Survey). The interviews included a history of
      frequency, type, and quantity of alcohol ingested. Serum samples were obtained
      after an overnight fast and 2 hours after ingestion of 75 grams of glucose for
      determination of glucose and insulin levels. Height and weight was measured for
      determination of body mass index. RESULTS: Participants who consumed alcohol
      daily had significantly lower fasting and 2-hour postglucose serum insulin
      concentrations compared with those who abstained from alcohol intake, when
      adjusted using linear logistic regression models for serum glucose concentration,
      gender, ethnicity, age, and body mass index. CONCLUSIONS: Abstainers with their
      relative hyperinsulinemia appear to be more insulin resistant than daily moderate
      drinkers. This difference in insulin sensitivity may explain the lower prevalence
      of diabetes in drinkers compared with abstainers observed in various
      epidemiological studies.

PMID- 14570867
TI  - Human ABCA7 supports apolipoprotein-mediated release of cellular cholesterol and
      phospholipid to generate high density lipoprotein.
AB  - Apolipoprotein-mediated release of cellular cholesterol and phospholipids was
      induced in HEK293 cells by expressing human ATP-binding cassette transporter A7
      (ABCA7) and ABC transporter A1 (ABCA1) proteins, whether transient or stable, to
      generate cholesterol-rich high density lipoprotein (HDL). Green fluorescent
      protein (GFP) attached at their C termini did not influence the lipid release
      reactions. Transfected ABCA7-GFP induced apolipoprotein-mediated assembly of
      cholesterol-containing HDL also in L929 cells, which otherwise generate only
      cholesterol-deficient HDL with their endogenous ABCA1. Time-dependent release of
      cholesterol and phospholipid by apolipoprotein A (apoA)-I was parallel both with
      ABCA1 and with ABCA7 when highly expressed in HEK293 cells, but dose-dependent
      profiles of lipid release on apoA-I and apoA-II were somewhat different between
      ABCA1 and ABCA7. Analyses of the stable clones with ABCA1-GFP (293/2c) and ABCA7
      GFP (293/6c) by using the same vector indicated some differences in regulation of
      their activities by protein kinase modulators. Dibutyryl cyclic AMP increased
      ABCA1-GFP and the release of cholesterol and phospholipid in 293/2c but increased
      neither ABCA7-GFP nor the lipid release in 293/6c. Expression of ABCA1-GFP- and
      apoA-I-mediated lipid release were enhanced in parallel by phorbol 12-myristate
      13-acetate (PMA) in 293/2c cells. In contrast, the same treatment of 293/6c
      increased ABCA7-GFP, but apoA-I-mediated lipid release was significantly
      suppressed. Despite these different responses to PMA, all of the effects of PMA
      were reversed by a specific protein kinase C inhibitor Go6976, suggesting that
      the changes were in fact due to protein kinase C activation. A thiol protease
      inhibitor, N-acetyl-Leu-Leu-norleucinal, increased the protein levels of ABCA1
      GFP in 293/2c and ABCA7-GFP in 293/6c, indicating their common degradation
      pathway. The data indicated that human ABCA7 would compensate the function of
      ABCA1 for release of cell cholesterol in a certain condition(s), but post
      transcriptional regulation of their activity is different.

PMID- 14570868
TI  - Phosphorylation of tumor necrosis factor receptor 1 (p55) protects macrophages
      from silica-induced apoptosis.
AB  - Macrophages play a fundamental role in silicosis in part by removing silica
      particles and producing inflammatory mediators in response to silica. Tumor
      necrosis factor alpha (TNFalpha) is a prominent mediator in silicosis. Silica
      induction of apoptosis in macrophages might be mediated by TNFalpha. However,
      TNFalpha also activates signal transduction pathways (NF-kappaB and AP-1) that
      rescue cells from apoptosis. Therefore, we studied the TNFalpha-mediated
      mechanisms that confer macrophage protection against the pro-apoptotic effects of
      silica. We will show that exposure to silica induced TNFalpha production by RAW
      264.7 cells, but not by IC-21. Silica-induced activation of NF-kappaB and AP-1
      was only observed in RAW 264.7 macrophages. ERK activation in response to silica
      exposure was only observed in RAW 264.7 macrophages, whereas activation of p38
      phosphorylation was predominantly observed in IC-21 macrophages. No changes in
      JNK activity were observed in either cell line in response to silica exposure.
      Silica induced apoptosis in both macrophage cell lines, but the induction of
      apoptosis was significantly larger in IC-21 cells. Protection against apoptosis
      in RAW 264.7 cells in response to silica was mediated by enhanced NF-kappaB
      activation and ERK-mediated phosphorylation of the p55 TNFalpha receptor.
      Inhibition of these two protective mechanisms by specific pharmacological
      inhibitors or transfection of dominant negative mutants that inhibit IkappaBalpha
      or ERK phosphorylation significantly increased silica-induced apoptosis in RAW
      264.7 macrophages. These data suggest that NF-kappaB activation and ERK-mediated
      phosphorylation of the p55 TNF receptor are important cell survival mechanisms in
      the macrophage response to silica exposure.

PMID- 14570869
TI  - Epitope tagging of the yeast K(+) carrier Trk2p demonstrates folding that is
      consistent with a channel-like structure.
AB  - TRK family proteins, which mediate the concentrative uptake of potassium by plant
      cells, fungi, and bacteria, resemble primitive potassium channels in sequence and
      have recently been proposed actually to fold like potassium channels in a 4-MPM
      motif (Durell, S. R., and Guy, H. R. (1999) Biophys. J. 77, 789 - 807), instead
      of like conventional substrate porters in the 12-TM motif (Gaber, R. F., Styles,
      C. A., and Fink, G. R. (1988) Mol. Cell. Biol. 8, 2848-2859). The known fungal
      members of this family possess a very long hydrophilic loop, positioned
      intracellularly in the K(+)-channel model and extracellularly in the substrate
      porter model. This and two shorter hydrophilic segments have been tested as
      topological markers for the true folding pattern of TRK proteins using
      Saccharomyces cerevisiae Trk2p. Hemagglutinin epitope tags were inserted into all
      three segments, and the enhanced green fluorescent protein (EGFP) was fused to
      the C terminus of Trk2p. The gene constructs were expressed from a high copy
      plasmid, and sidedness of the tags was determined by native fluorescence (EGFP),
      indirect immunofluorescence, and immunoelectron microscopy. Both the long-loop
      tag and the C-terminal EGFP fusion allowed abundant protein to reach the plasma
      membrane and support normal yeast growth. In all determinations, the long-loop
      tag was localized to the inner surface of the yeast cell plasma membrane, thus
      strongly supporting the channel-like folding model. Additional observations
      showed (i). membrane-associated Trk2p to lie in proteolipid rafts; (ii).
      significant tagged protein, expressed from the plasmid, to be sequestered in
      cytoplasmic vesicular-tubular clusters; and (iii). suppression of such clusters
      by yeast growth in 5-10% glycerol. This chaperone-like effect may assist other
      membrane proteins (overexpressed or heterologously expressed) to function within
      the yeast plasma membrane.

PMID- 14570870
TI  - Sphingosine-phosphate lyase enhances stress-induced ceramide generation and
      apoptosis.
AB  - Sphingosine-1-phosphate lyase is a widely expressed enzyme that catalyzes the
      essentially irreversible cleavage of the signaling molecule sphingosine 1
      phosphate. To investigate whether sphingosine-1-phosphate lyase influences
      mammalian cell fate decisions, a recombinant human sphingosine-1-phosphate lyase
      fused to green fluorescent protein was expressed in HEK293 cells. The recombinant
      enzyme was active, localized to the endoplasmic reticulum, and reduced baseline
      sphingosine and sphingosine 1-phosphate levels. Stable overexpression led to
      diminished viability under stress, which was attributed to an increase in
      apoptosis and was reversible in a dose-dependent manner by exogenous sphingosine
      1-phosphate. In contrast to sphingosine 1-phosphate, the products of the lyase
      reaction had no effect on apoptosis. Lyase enzymatic activity was required to
      potentiate apoptosis, because cells expressing a catalytically inactive enzyme
      behaved like controls. Stress increased the amounts of long- and very long-chain
      ceramides in HEK293 cells, and this was enhanced in cells overexpressing wild
      type but not catalytically inactive lyase. The ceramide increases appeared to be
      required for apoptosis, because inhibition of ceramide synthase with fumonisin B1
      decreased apoptosis in lyase-overexpressing cells. Thus, sphingosine-1-phosphate
      lyase overexpression in HEK293 cells decreases sphingosine and sphingosine 1
      phosphate amounts but elevates stress-induced ceramide generation and apoptosis.
      This identifies sphingosine-1-phosphate lyase as a dual modulator of sphingosine
      1-phosphate and ceramide metabolism as well as a regulator of cell fate decisions
      and, hence, a potential target for diseases with an imbalance in these
      biomodulators, such as cancer.

PMID- 14570871
TI  - Regulatory mechanism of Dictyostelium myosin light chain kinase A.
AB  - In this study, we examined the activation mechanism of Dictyostelium myosin light
      chain kinase A (MLCK-A) using constitutively active Ca2+/calmodulin-dependent
      protein kinase kinase as a surrogate MLCK-A kinase. MLCK-A was phosphorylated at
      Thr166 by constitutively active Ca2+/calmodulin-dependent protein kinase kinase,
      resulting in an approximately 140-fold increase in catalytic activity, using
      intact Dictyostelium myosin II. Recombinant Dictyostelium myosin II regulatory
      light chain and Kemptamide were also readily phosphorylated by activated MLCK-A.
      Mass spectrometry analysis revealed that MLCK-A expressed by Escherichia coli was
      autophosphorylated at Thr289 and that, subsequent to Thr166 phosphorylation, MLCK
      A also underwent a slow rate of autophosphorylation at multiple Ser residues.
      Using site-directed mutagenesis, we show that autophosphorylation at Thr289 is
      required for efficient phosphorylation and activation by an upstream kinase. By
      performing enzyme kinetics analysis on a series of MLCK-A truncation mutants, we
      found that residues 283-288 function as an autoinhibitory domain and that
      autoinhibition is fully relieved by Thr166 phosphorylation. Simple removal of
      this region resulted in a significant increase in the kcat of MLCK-A; however, it
      did not generate maximum enzymatic activity. Together with the results of our
      kinetic analysis of the enzymes, these findings demonstrate that Thr166
      phosphorylation of MLCK-A by an upstream kinase subsequent to autophosphorylation
      at Thr289 results in generation of maximum MLCK-A activity through both release
      of an autoinhibitory domain from its catalytic core and a further increase (15-19
      fold) in the kcat of the enzyme.

PMID- 14570872
TI  - Calcium-binding protein 1 is an inhibitor of agonist-evoked, inositol 1,4,5
      trisphosphate-mediated calcium signaling.
AB  - Intracellular calcium signals are responsible for initiating a spectrum of
      physiological responses. The caldendrins/calcium-binding proteins (CaBPs)
      represent mammal-specific members of the CaM superfamily. CaBPs display a
      restricted pattern of expression in neuronal/retinal tissues, suggesting a
      specialized role in Ca2+ signaling in these cell types. Recently, it was reported
      that a splice variant of CaBP1 functionally interacts with inositol 1,4,5
      trisphosphate (InsP3) receptors to elicit channel activation in the absence of
      InsP3 (Yang, J., McBride, S., Mak, D.-O. D., Vardi, N., Palczewski, K.,
      Haeseleer, F., and Foskett, J. K. (2002) Proc. Natl. Acad. Sci. U. S. A. 99, 7711
      7716). These data indicate a new mode of InsP3 receptor modulation and hence
      control of intracellular Ca2+ concentration ([Ca2+]i) in neuronal tissues. We
      have analyzed the biochemistry of the long form splice variant of CaBP1 (L-CaBP1)
      and show that, in vitro, a recombinant form of the protein is able to bind Ca2+
      with high affinity and undergo a conformational change. We also describe the
      localization of endogenous and overexpressed L-CaBP1 in the model neuroendocrine
      PC12 cell system, where it was associated with the plasma membrane and Golgi
      complex in a myristoylation-dependent manner. Furthermore, we show that
      overexpressed L-CaBP1 is able to substantially suppress rises in [Ca2+]i in
      response to physiological agonists acting on purinergic receptors and that this
      inhibition is due in large part to blockade of release from intracellular Ca2+
      stores. The related protein neuronal calcium sensor-1 was without effect on the
      [Ca2+]i responses to agonist stimulation. Measurement of [Ca2+] within the ER of
      permeabilized PC12 cells demonstrated that LCaBP1 directly inhibited InsP3
      mediated Ca2+ release. Expression of L-CaBP1 also inhibited histamine-induced
      [Ca2+]i oscillations in HeLa cells. Together, these data suggest that L-CaBP1 is
      able to specifically regulate InsP3 receptor-mediated alterations in [Ca2+]i
      during agonist stimulation.

PMID- 14570873
TI  - Synthesis and biophysical characterization of a multidomain peptide from a
      Saccharomyces cerevisiae G protein-coupled receptor.
AB  - We attached peptides corresponding to the seventh transmembrane domain (TMD7) of
      the alpha-mating factor receptor (Ste2p) of Saccharomyces cerevisiae to a
      hydrophilic, 40-residue fragment of the carboxyl terminus of this G protein
      coupled receptor. Peptides corresponding to (a) the 40-residue portion of the
      carboxyl tail (T-40), (b) the tail plus a part of TMD7 (M7-12-T40), and (c) to
      the tail plus the full TMD7 (M7-24-T40) were chemically synthesized and purified.
      The molecular mass and primary sequence of these peptides were confirmed by mass
      spectrometry and tandem mass spectrometry procedures. Circular dichroism (CD)
      revealed that T-40 was disordered in phosphate buffer and in the presence of 1,2
      dimyristoyl-sn-glycero-3-phosphocholine/1,2-dimyristoyl-sn-glycero-3-[phospho
      racemic-(1-glycerol)] bilayers. In contrast, M7-12-T40 and M7-24-T40 peptides
      were partially helical in the presence of vesicles, and difference CD
      spectroscopy showed that the transmembrane regions of these peptides were 42 and
      94% helical, respectively. CD analysis also demonstrated that M7-24-T40 retained
      its secondary structure in the presence of 1-palmitoyl-2-hydroxy-sn-glycero-3
      [phospho-racemic-(1-glycerol)] micelles at 0.5 mm concentration. Thus, the tail
      and the transmembrane domain of the multidomain 64-amino acid residue peptide
      manifest individual conformational preferences. Measurement of tryptophan
      fluorescence indicated that the transmembrane domain integrated into bilayers in
      a manner similar to that expected for this region in the native state of the
      receptor. This study demonstrated that the tail of Ste2p can be used as a
      hydrophilic template to study transmembrane domain structure using techniques
      such as CD and NMR spectroscopy.

PMID- 14570874
TI  - Stress-induced premature senescence in hTERT-expressing ataxia telangiectasia
      fibroblasts.
AB  - In addition to replicative senescence, normal diploid fibroblasts undergo stress
      induced premature senescence (SIPS) in response to DNA damage caused by oxidative
      stress or ionizing radiation (IR). SIPS is not prevented by telomere elongation,
      indicating that, unlike replicative senescence, it is triggered by nonspecific
      genome-wide DNA damage rather than by telomere shortening. ATM, the product of
      the gene mutated in individuals with ataxia telangiectasia (AT), plays a central
      role in cell cycle arrest in response to DNA damage. Whether ATM also mediates
      signaling that leads to SIPS was investigated with the use of normal and AT
      fibroblasts stably transfected with an expression vector for the catalytic
      subunit of human telomerase (hTERT). Expression of hTERT in AT fibroblasts
      resulted in telomere elongation and prevented premature replicative senescence,
      but it did not rescue the defect in G(1) checkpoint activation or the
      hypersensitivity of the cells to IR. Despite these remaining defects in the DNA
      damage response, hTERT-expressing AT fibroblasts exhibited characteristics of
      senescence on exposure to IR or H(2)O(2) in such a manner that triggers SIPS in
      normal fibroblasts. These characteristics included the adoption of an enlarged
      and flattened morphology, positive staining for senescence-associated beta
      galactosidase activity, termination of DNA synthesis, and accumulation of p53,
      p21(WAF1), and p16(INK4A). The phosphorylation of p38 mitogen-activated protein
      kinase (p38 MAPK), which mediates signaling that leads to senescence, was also
      detected in both IR- or H(2)O(2)-treated AT and normal fibroblasts expressing
      hTERT. These results suggest that the ATM-dependent signaling pathway triggered
      by DNA damage is dispensable for activation of p38 MAPK and SIPS in response to
      IR or oxidative stress.

PMID- 14570876
TI  - Rab2 interacts directly with atypical protein kinase C (aPKC) iota/lambda and
      inhibits aPKCiota/lambda-dependent glyceraldehyde-3-phosphate dehydrogenase
      phosphorylation.
AB  - Atypical protein kinase C iota/lambda (PKCiota/lambda) is essential for protein
      transport in the early secretory pathway. The small GTPase Rab2 selectively
      recruits the kinase to vesicular tubular clusters (VTCs) where PKCiota/lambda
      phosphorylates glyceraldehyde-3-phosphate dehydrogenase (GAPDH). VTCs are
      composed of small vesicles and tubules and serve as transport intermediates that
      shuttle cargo from the endoplasmic reticulum to the Golgi complex. These
      structures are the first site of segregation of the anterograde and retrograde
      pathways. When Rab2 binds to a VTC subcompartment, the subsequent recruitment of
      PKCiota/lambda and soluble components, including COPI (coatomer and ADP
      ribosylation factor), results in the release of retrograde-directed vesicles.
      Because Rab2 stimulates PKCiota/lambda membrane association in a dose-dependent
      manner, we investigated whether the two proteins physically interact. Using a
      combination of in vivo and in vitro assays, we found that Rab2 interacts directly
      with PKCiota/lambda and that this interaction occurs through the Rab2 amino
      terminus (residues 1-19) and the PKCiota/lambda regulatory domain. A mutant
      lacking the PKCiota/lambda binding domain (Rab2N'Delta19) was functionally
      characterized. In contrast to Rab2, Rab2N'Delta19 failed to recruit
      PKCiota/lambda to normal rat kidney microsomes in a quantitative binding assay.
      To determine whether Rab2 modulates the ability of PKCiota/lambda to
      phosphorylate GAPDH, an in vitro kinase assay was supplemented with Rab2 or
      Rab2N'Delta19. Rab2 inhibited PKCiota/lambda-dependent GAPDH phosphorylation,
      whereas no effect was observed when the assay was performed with the
      aminoterminal truncation mutant. These results suggest that a downstream effector
      recruited to the VTC stimulates PKCiota/lambda-mediated GAPDH phosphorylation by
      alleviating the inhibition imposed by Rab2-PKCiota/lambda interaction.

PMID- 14570875
TI  - The homologous region sequence (hr1) of Autographa californica multinucleocapsid
      polyhedrosis virus can enhance transcription from non-baculoviral promoters in
      mammalian cells.
AB  - The Autographa californica multinucleocapsid polyhedrosis virus homologous region
      sequence hr1 enhances transcription from the viral polyhedrin promoter in
      Spodoptera frugiperda insect cells and independently functions as an origin of
      replication (ori) sequence. The binding of the host nuclear protein, hr1-binding
      protein (hr1-BP), is crucial for the enhancer activity (Habib, S., Pandey, S.,
      Chatterji, U., Burma, S., Ahmad, R., Jain, A., and Hasnain, S. E. (1996) DNA Cell
      Biol. 15, 737-747 and Habib, S., and Hasnain, S. E. (1996) J. Biol. Chem. 271,
      28250-28258). We demonstrate that hr1 can also enhance transcription from non
      baculoviral promoters like cytomegalovirus and hsp70 in mammalian cells but does
      not support ori activity in these cells. Unlike insect cells, hr1 can also
      function in mammalian cells as an enhancer when present in trans. hr1 DNA
      sequence binds with high affinity and specificity to nuclear factors in the
      mammalian cells. The insect hr1-BP- and the hr1-BP-like proteins from mammalian
      cells (mhr1-BP) have different properties with respect to ion requirements, DNA
      groove binding, and molecular size. When mammalian cells are infected with a
      recombinant baculovirus containing two promoters, the baculovirus polyhedrin and
      Drosophila hsp70 gene promoter, the hsp70 gene promoter alone is active in these
      cells, and this activity is further enhanced by the presence of an additional hr1
      in the recombinant virus. hr1 may thus also have a role in baculovirus-mediated
      gene delivery in mammalian cells.

PMID- 14570877
TI  - The yeast RNA-binding protein Rbp1p modifies the stability of mitochondrial porin
      mRNA.
AB  - The Saccharomyces cerevisiae RNA-binding protein Rbp1p was initially identified
      as a negative growth regulator; however, its function is still obscure. Here, we
      show that Rbp1p in cells is associated with structures that sediment at 10,000 as
      well as 100,000 x g. It appears microscopically as punctate signals partially
      localized to the perinuclear region. Over-expression of Rbp1p in yeast resulted
      in growth defects on nonfermentable carbon sources, suggesting a function for
      Rbp1p in mitochondrial biogenesis. Absence of Rbp1p increased the level of
      mitochondrial porin, whereas over-expression of Rbp1p, but not an N-terminally
      truncated form, decreased porin levels. Over-expression of Rbp1p also decreased
      the level of mitochondrial porin mRNA by enhancing its degradation, an effect
      that was dependent on all three of the Rbp1p RNA recognition motifs. In cells,
      the porin mRNA is associated with Rbp1p.RNP (ribonucleoprotein) complexes. In
      vitro binding assays showed that Rbp1p most likely interacts with a (C/G)U-rich
      element in the porin mRNA 3'-UTR. Based on these observations, we infer that
      Rbp1p has a role in negatively regulating mitochondrial porin expression post
      transcriptionally.

PMID- 14570878
TI  - Mechanistic studies on three 2-oxoglutarate-dependent oxygenases of flavonoid
      biosynthesis: anthocyanidin synthase, flavonol synthase, and flavanone 3beta
      hydroxylase.
AB  - Anthocyanidin synthase (ANS), flavonol synthase (FLS), and flavanone 3beta
      hydroxylase (FHT) are involved in the biosynthesis of flavonoids in plants and
      are all members of the family of 2-oxoglutarate- and ferrous iron-dependent
      oxygenases. ANS, FLS, and FHT are closely related by sequence and catalyze
      oxidation of the flavonoid "C ring"; they have been shown to have overlapping
      substrate and product selectivities. In the initial steps of catalysis, 2
      oxoglutarate and dioxygen are thought to react at the ferrous iron center
      producing succinate, carbon dioxide, and a reactive ferryl intermediate, the
      latter of which can then affect oxidation of the flavonoid substrate. Here we
      describe work on ANS, FLS, and FHT utilizing several different substrates carried
      out in 18O2/16OH2, 16O2/18OH2, and 18O2/18OH2 atmospheres. In the 18O2/16OH2
      atmosphere close to complete incorporation of a single 18O label was observed in
      the dihydroflavonol products (e.g. (2R,3R)-trans-dihydrokaempferol) from
      incubations of flavanones (e.g. (2S)naringenin) with FHT, ANS, and FLS. This and
      other evidence supports the intermediacy of a reactive oxidizing species, the
      oxygen of which does not exchange with that of water. In the case of products
      formed by oxidation of flavonoid substrates with a C-3 hydroxyl group (e.g.
      (2R,3R)-trans-dihydroquercetin), the results imply that oxygen exchange can occur
      at a stage subsequent to initial oxidation of the C-ring, probably via an enzyme
      bound C-3 ketone/3,3-gem-diol intermediate.

PMID- 14570879
TI  - An Arabidopsis RNA lariat debranching enzyme is essential for embryogenesis.
AB  - An embryo-defective mutant of Arabidopsis thaliana was isolated that arrests
      development at a variety of stages, from as early as the globular stage of
      embryogenesis to as late as formation of an abnormal bent cotyledon stage embryo.
      Defects in the suspensor, a normally transient structure derived from the
      fertilized egg, were often associated with the arrested embryo. The lesion was
      within a gene encoding a protein with domains characteristic of lariat
      debranching enzymes, which has been named AtDBR1 (for Arabidopsis thaliana
      Debranching enzyme 1). Cleavage of the 2'-5'-phosphodiester bond found in excised
      intron lariats ("debranching") is essential for turnover of intronic sequences as
      well as generation of some small nucleolar RNAs. The mutation within AtDBR1 was
      confirmed by complementation as being responsible for the embryo-lethal
      phenotype, and the activity of the encoded protein in cleavage of 2'-5'
      phosphodiester bonds was verified using an in vitro debranching assay.

PMID- 14570880
TI  - Hsp90 inhibition depletes Chk1 and sensitizes tumor cells to replication stress.
AB  - DNA damage and replication stress activate the Chk1 signaling pathway, which
      blocks S phase progression, stabilizes stalled replication forks, and
      participates in G2 arrest. In this study, we show that Chk1 interacts with Hsp90,
      a molecular chaperone that participates in the folding, assembly, maturation, and
      stabilization of specific proteins known as clients. Consistent with Chk1 being
      an Hsp90 client, we also found that Chk1 but not Chk2 is destabilized in cells
      treated with the Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG).
      17-AAG-mediated Chk1 loss blocked the ability of Chk1 to target Cdc25A for
      proteolytic destruction, demonstrating that the Chk1 signaling pathway was
      disrupted in the 17-AAG-treated cells. Finally, 17-AAG-mediated disruption of
      Chk1 activation dramatically sensitized various tumor cells to gemcitabine, an S
      phase-active chemotherapeutic agent. Collectively, our studies identify Chk1 as a
      novel Hsp90 client and suggest that pharmacologic inhibition of Hsp90 may
      sensitize tumor cells to chemotherapeutic agents by disrupting Chk1 function
      during replication stress.

PMID- 14570881
TI  - Variation of high mannose chains of Tamm-Horsfall glycoprotein confers
      differential binding to type 1-fimbriated Escherichia coli.
AB  - Tamm-Horsfall glycoprotein (THP), the most abundant protein in mammalian urine,
      has been implicated in defending the urinary tract against infections by type 1
      fimbriated Escherichia coli. Recent experimental evidence indicates that the
      defensive capability of THP relies on its single high mannose chain, which binds
      to E. coli FimH lectin and competes with mannosylated uroplakin receptors on the
      bladder surface. Here we describe several major differences, on both structural
      and functional levels, between human THP (hTHP) and pig THP (pTHP). pTHP contains
      a much higher proportion (47%) of Man5GlcNAc2 than does hTHP (8%). FimH
      expressing E. coli adhere to monomeric pTHP at an approximately 3-fold higher
      level than to monomeric hTHP. This suggests that the shorter high mannose chain
      (Man5GlcNAc2) is a much better binder for FimH than the longer chains (Man6
      7GlcNAc2) and that pTHP is a more potent urinary defense factor than hTHP. In
      addition, unlike hTHP whose polyantennary glycans are exclusively capped by
      sialic acid and sulfate groups, those of pTHP are also terminated by
      Galalpha1,3Gal epitope. This is consistent with the fact that the outer medulla
      of pig kidney expresses the alpha1,3-galactosyltransferase, which is completely
      absent in human kidney. Finally, pTHP is more resistant to leukocyte elastase
      hydrolysis than hTHP, thus explaining why pTHP is much less prone to urinary
      degradation than hTHP. These results demonstrate for the first time that the
      species variations of the glycomoiety of THP can lead to the differential binding
      of THP to type 1-fimbriated E. coli and that the differences in high mannose
      processing may reflect species-specific adaptation of urinary defenses against E.
      coli infections.

PMID- 14570882
TI  - Molecular basis of the amylose-like polymer formation catalyzed by Neisseria
      polysaccharea amylosucrase.
AB  - Amylosucrase from Neisseria polysaccharea is a remarkable transglucosidase from
      family 13 of the glycoside-hydrolases that synthesizes an insoluble amylose-like
      polymer from sucrose in the absence of any primer. Amylosucrase shares strong
      structural similarities with alpha-amylases. Exactly how this enzyme catalyzes
      the formation of alpha-1,4-glucan and which structural features are involved in
      this unique functionality existing in family 13 are important questions still not
      fully answered. Here, we provide evidence that amylosucrase initializes polymer
      formation by releasing, through sucrose hydrolysis, a glucose molecule that is
      subsequently used as the first acceptor molecule. Maltooligosaccharides of
      increasing size were produced and successively elongated at their nonreducing
      ends until they reached a critical size and concentration, causing precipitation.
      The ability of amylosucrase to bind and to elongate maltooligosaccharides is
      notably due to the presence of key residues at the OB1 acceptor binding site that
      contribute strongly to the guidance (Arg415, subsite +4) and the correct
      positioning (Asp394 and Arg446, subsite +1) of acceptor molecules. On the other
      hand, Arg226 (subsites +2/+3) limits the binding of maltooligosaccharides,
      resulting in the accumulation of small products (G to G3) in the medium. A
      remarkable mutant (R226A), activated by the products it forms, was generated. It
      yields twice as much insoluble glucan as the wild-type enzyme and leads to the
      production of lower quantities of by-products.

PMID- 14570883
TI  - A brief historical review of the waterfall/cascade of blood coagulation.

PMID- 14570884
TI  - Overexpression of SR-BI by adenoviral vector reverses the fibrateinduced
      hypercholesterolemia of apolipoprotein E-deficient mice.
AB  - The hypercholesterolemia characteristic of apolipoprotein (apoE)-deficient mice
      fed on a regular chow diet is caused by the abnormal accumulation of apoB-48
      carrying remnants of chylomicrons and very low density lipoproteins in the
      plasma. Treatment of apoE-deficient mice with ciprofibrate or other peroxisome
      proliferator-activated receptor alpha agonists severely aggravates their
      hypercholesterolemia by interfering with one or more mechanisms of remnant
      removal from the circulation that do not require mediation by apoE (Fu, T.,
      Kashireddy, P., and Borensztajn, J. (2003) Biochem. J. 373, 941-947). In the
      present investigation we report that ciprofibrate treatment causes the down
      regulation of hepatic scavenger receptor class B, type I (SR-BI) protein
      expression in the livers of apoE-deficient mice. On cessation of the treatment SR
      BI expression returns to its pretreatment levels, coinciding with a reversal of
      the hypercholesterolemia to base-line concentrations. Restoration of SR-BI
      expression in ciprofibrate-treated apoE-deficient mice by recombinant adenoviral
      gene transfer abolishes the ciprofibrate-induced over accumulation of apoB-48
      carrying remnants in the plasma. We also report that remnants isolated from the
      plasma of ciprofibrate-treated apoE-deficient mice bind to murine SR-BI expressed
      in stably transfected cultured cells. These observations suggest that, in
      addition to its well established role as high density lipoprotein receptor, SR-BI
      can also function as a remnant receptor responsible for the clearance of remnants
      from the circulation of apoE-deficient mice.

PMID- 14570885
TI  - Structure-activity relationship of synthetic toll-like receptor 4 agonists.
AB  - Important questions remain regarding the impact of variations in the structure of
      the lipid A portion of lipopolysaccharide on activation of cells via the Toll
      like receptor 4 complex. We have studied a series of synthetic lipid A mimetic
      compounds known as aminoalkyl glucosaminide phosphates in which the length of the
      secondary acyl chain has been systematically varied. Using transcriptional
      profiling of human monocytes and responses of Toll-like receptor 4 complex cell
      transfectants, we demonstrate a clear dependence of length on secondary acyl
      chain on Toll-like receptor 4 activation. Compounds with secondary acyl chains
      less than eight carbons in length have dramatically reduced activity, and
      substitutions of the left-sided secondary acyl chain had the most important
      effect on the Toll-like receptor 4 agonist activity of these molecules. The
      structure-function relationships of these compounds assessed via the induction of
      chemokines and cytokines following in vivo administration closely mirrored those
      seen with cell-based studies. This novel set of synthetic lipid A mimetics will
      be useful for Toll-like receptor 4-based investigations and may have clinical
      utility as stand-alone immunomodulators.

PMID- 14570886
TI  - Enhancement of tyrosine hydroxylase phosphorylation and activity by glial cell
      line-derived neurotrophic factor.
AB  - Although glial cell-line derived neurotrophic factor (GDNF) acts as a potent
      survival factor for dopaminergic neurons, it is not known whether GDNF can
      directly alter dopamine synthesis. Tyrosine hydroxylase (TH) is the rate-limiting
      enzyme for dopamine biosynthesis, and its activity is regulated by
      phosphorylation on three seryl residues: Ser-19, Ser-31, and Ser-40. Using a TH
      expressing human neuroblastoma cell line and rat primary mesencephalic neuron
      cultures, the present study examined whether GDNF alters the phosphorylation of
      TH and whether these changes are accompanied by increased enzymatic activity.
      Exposure to GDNF did not alter the TH protein level in either neuroblastoma cells
      or in primary neurons. However, significant increases in the phosphorylation of
      Ser-31 and Ser-40 were detected within minutes of GDNF application in both cell
      types. Enhanced Ser-31 and Ser-40 phosphorylation was associated with increased
      TH activity but not dopamine synthesis in neuroblastoma cells, possibly because
      of the absence of l-aromatic amino acid decarboxylase activity in these cells. In
      contrast, increased phosphorylation of Ser-31 and Ser-40 was found to enhance
      dopamine synthesis in primary neurons. Pharmacological experiments show that Erk
      and protein kinase A phosphorylate Ser-31 and Ser-40, respectively, and that
      their inhibition blocked both TH phosphorylation and activity. Our results
      indicate that, in addition to its role as a survival factor for dopaminergic
      neurons, GDNF can directly increase dopamine synthesis.

PMID- 14570887
TI  - Genes malh and pagl of Clostridium acetobutylicum ATCC 824 encode NAD+- and Mn2+
      dependent phospho-alpha-glucosidase(s).
AB  - The genome of Clostridium acetobutylicum 824 contains two genes encoding NAD+,
      Mn2+, and dithiothreitol-dependent phospho-alpha-glucosidases that can be
      assigned to family 4 of the glycosylhydrolase superfamily. The two genes,
      designated malh (maltose 6-phosphate hydrolase) and pagl (phospho-alpha
      glucosidase), respectively, reside in separate operons that also encode proteins
      of the phosphoenolpyruvate-dependent:sugar phosphotransferase system. C.
      acetobutylicum grows on a variety of alpha-linked glucosides, including maltose,
      methyl-alpha-d-glucoside, and the five isomers of sucrose. In the presence of the
      requisite cofactors, extracts of these cells readily hydrolyzed the chromogenic
      substrate p-nitrophenyl-alpha-d-glucopyranoside 6-phosphate, but whether
      hydrolysis reflected expression of enzymes encoded by the malh or pagl genes was
      not discernible by spectrophotometric analysis or polyacrylamide gel
      electrophoresis. Resolution of this question required the cloning of the malh and
      pagl genes, and subsequent high expression, purification, and characterization of
      maltose-6'-phosphate hydrolase (MalH) and phospho-alpha-glucosidase (PagL),
      respectively. MalH and PagL exhibit 50% residue identity, and in solution are
      tetramers comprising similar sized ( approximately 50 kDa) subunits. The two
      proteins cross-react with polyclonal rabbit antibody against phospho-alpha
      glucosidase from Fusobacterium mortiferum. Purified MalH and PagL cleaved p
      nitrophenyl-alpha-d-glucopyranoside 6-phosphate with comparable efficiency, but
      only MalH catalyzed the hydrolysis of disaccharide 6'-phosphates formed via the
      phosphoenolpyruvate-dependent:sugar phosphotransferase system. Importantly,
      analysis of the proteome of C. acetobutylicum 824 by electrospray ionization-mass
      spectrometry confirmed expression of MalH during growth on many alpha-glucosides
      tested. Site-directed changes C169S and D170N yielded full-length, but
      catalytically inactive MalH. Of the two putative operons, our findings suggest
      that only proteins encoded by the mal operon participate in the dissimilation of
      maltose and related O-alpha-linked glucosides by C. acetobutylicum 824.

PMID- 14570888
TI  - Regulation of the dual specificity protein phosphatase, DsPTP1, through
      interactions with calmodulin.
AB  - Reversible phosphorylation is a key mechanism for the control of intercellular
      events in eukaryotic cells. In animal cells, Ca2+/CaM-dependent protein
      phosphorylation and dephosphorylation are implicated in the regulation of a
      number of cellular processes. However, little is known on the functions of
      Ca2+/CaM-dependent protein kinases and phosphatases in Ca2+ signaling in plants.
      From an Arabidopsis expression library, we isolated cDNA encoding a dual
      specificity protein phosphatase 1, which is capable of hydrolyzing both
      phosphoserine/threonine and phosphotyrosine residues of the substrates. Using a
      gel overlay assay, we identified two Ca2+-dependent CaM binding domains (CaMBDI
      in the N terminus and CaMBDII in the C terminus). Specific binding of CaM to two
      CaMBD was confirmed by site-directed mutagenesis, a gel mobility shift assay, and
      a competition assay using a Ca2+/CaM-dependent enzyme. At increasing
      concentrations of CaM, the biochemical activity of dual specificity protein
      phosphatase 1 on the p-nitrophenyl phosphate (pNPP) substrate was increased,
      whereas activity on the phosphotyrosine of myelin basic protein (MBP) was
      inhibited. Our results collectively indicate that calmodulin differentially
      regulates the activity of protein phosphatase, dependent on the substrate. Based
      on these findings, we propose that the Ca2+ signaling pathway is mediated by CaM
      cross-talks with a protein phosphorylation signal pathway in plants via protein
      dephosphorylation.

PMID- 14570889
TI  - Identification of a new cross-link and unique histidine adduct from bovine serum
      albumin incubated with malondialdehyde.
AB  - Malondialdehyde, acetaldehyde, acrolein, and 4-hydroxynonenal are all products of
      fatty acid oxidation found in the fatty streaks of atherosclerotic arteries due
      to a lack of antioxidants and an increase in glycation products. Previously
      identified cross-links derived from these molecules have nearly always required
      more than one molecule of each type, although this is physiologically less likely
      than a reaction involving a single molecule. Here we provide indirect but strong
      evidence for a malondialdehyde-derived cross-link requiring just one
      malondialdehyde molecule to link arginine and lysine, giving 2-ornithinyl-4
      methyl(1epsilon-lysyl)1,3-imidazole following a 4-day incubation of albumin with
      8 mm malondialdehyde. This cross-link was identified as its partial degradation
      product Nepsilon-(2-carboxyl,2-aminoethane)-Nepsilon-methanoyl-lysine by NMR and
      mass spectrometry. Analysis of plasma from treated diabetic patients revealed
      that one patient levels had as high as 0.46%, 0.67% of their lysine/arginine
      residues modified by this cross-link, although others had lower levels. Alkaline
      hydrolysis of serum albumin also revealed two acid-labile malondialdehyde adducts
      of histidine in significant quantities, the isomers 4- and 2-ethylidene
      histidine. These constituted up to 0.93% of the histidines in treated diabetic
      patients. Although collagen is readily cross-linked by malondialdehyde, none of
      these particular products could be found in incubations of collagen with
      malondialdehyde.

PMID- 14570890
TI  - Mice expressing only covalent dimeric heparin binding-deficient lipoprotein
      lipase: muscles inefficiently secrete dimeric enzyme.
AB  - Lipoprotein lipase (LpL) hydrolyzes triglycerides of circulating lipoproteins
      while bound as homodimers to endothelial cell surface heparan sulfate
      proteoglycans. This primarily occurs in the capillary beds of muscle and adipose
      tissue. By creating a mouse line that expresses covalent dimers of heparin
      binding deficient LpL (hLpLHBM-Dimer) in muscle, we confirmed in vivo that
      linking two LpL monomers in a head to tail configuration creates a functional
      LpL. The hLpLHBM-Dimer transgene produced abundant activity and protein in
      muscle, and the LpL was the expected size of a dimer (approximately 110 kDa).
      Unlike the heparin-binding mutant monomer, hLpLHBM-Dimer had the same stability
      as nonmutated LpL. The hLpLHBM-Dimer transgene prevented the neonatal demise of
      LpL knockout mice; however, these mice were hypertriglyceridemic. Postheparin
      plasma LpL activity was lower than expected with the robust expression in muscle
      and was no longer covalently linked. Studies in transfected cells showed that
      Chinese hamster lung cells, but not COS cells, also degraded tandem repeated LpL
      into monomers. Thus, although muscle can synthesize tethered, dimeric LpL,
      efficient production of this enzyme leading to secretion, and physiological
      function appears to favor secretion of a noncovalent dimer composed of monomeric
      subunits.

PMID- 14570891
TI  - Transcriptional regulation of insulin-like growth factor-I by interferon-gamma
      requires STAT-5b.
AB  - Insulin-like growth factor (IGF)-I, a growth factor important for cell
      proliferation, cellular differentiation, and multiple metabolic functions, is
      regulated in vivo by growth factors and cytokines, but the mechanism(s) of
      regulation at the cellular level is not well understood. We now demonstrate,
      employing primary human dermal fibroblasts (CF), that the multipotent cytokine,
      interferon-gamma (IFN-gamma), can up-regulate IGF-I mRNA expression and that this
      regulation occurs via activation of the signal transducer and activator of
      transcription-5b (STAT-5b) pathway. IFN-gamma (100 units/ml) treatment of CF
      cells resulted in a preferential, time-dependent activation of STAT-5b, although
      both STAT-5a and STAT-5b isoforms are present. The activated STAT-5b translocated
      to the nucleus within 30 min of treatment and induced an increase in IGF-I mRNA
      of 6 +/- 1.0-fold, 3 h post-treatment, with a further increase to 8 +/- 1.7-fold
      at 5 h. In contrast, IFN-gamma treatment of primary human dermal fibroblasts with
      a nonfunctional STAT-5b (PF cells) resulted in activation of only STAT-5a and an
      increase of the IGF-I mRNA level of 1.7 +/- 0.6-fold, 5 h post-treatment. The IFN
      gamma-induced regulation of the interferon regulatory factor-1 gene, whose
      expression is dependent on activated STAT-1, was the same between CF and PF
      cells. In summary, our results provide evidence of the following in human primary
      dermal fibroblasts: (a). IFN-gamma preferentially activates STAT-5b, but, in the
      absence of a functional STAT-5b, STAT-5a is activated; (b). IFN-gamma time
      dependently up-regulates IGF-I mRNA expression; (c). the regulation of IGF-I
      requires an active STAT-5b, and activated STAT-5a cannot substitute for an
      inactive STAT-5b; and (d). STAT-5b has an essential role in the transcriptional
      up-regulation of IGF-I.

PMID- 14570892
TI  - Primary cultured neurons devoid of cellular prion display lower responsiveness to
      staurosporine through the control of p53 at both transcriptional and post
      transcriptional levels.
AB  - We assessed the contribution of the cellular prion protein (PrPc) in the control
      of neuronal apoptosis by examining cell death in both human cells and murine
      primary cultured neurons. We first confirmed our previous finding that
      staurosporine-induced caspase activation is increased by PrPc overexpression in
      HEK293 cells. We show here that this phenotype is fully dependent on p53 and that
      the control of p53 activity by PrPc occurs at both transcriptional and post
      transcriptional levels in human cells. Of most interest, we demonstrate that
      neuronal endogenous PrPc also controls a p53-dependent pro-apoptotic phenotype.
      Thus, DNA fragmentation and TUNEL (terminal deoxynucleotidyltransferase-mediated
      dUTP nick end-labeling)-positive cells were lower in primary cultured neurons
      derived from Zrch-1 mice embryos in which PrPc has been abrogated than in wild
      type neurons. PrPc knock-out neurons also displayed drastically diminished
      caspase-3-like activity and immunoreactivity together with reduced p53 expression
      and transcriptional activity, a phenotype complemented in part by PrPc
      transfection. Interestingly, p53 expression was also reduced in the brain of
      adult Prnp-/- mice. Neuronal PrPc likely controls p53 at a post-transcriptional
      level because the deletion of cellular prion protein is accompanied by a higher
      Mdm2-like immunoreactivity and reduced phosphorylated p38 MAPK expression. We
      therefore propose that the physiological function of endogenous cellular prion
      could be to regulate p53-dependent caspase-3-mediated neuronal cell death. This
      phenotype likely occurs through up-regulation of p53 promoter transactivation as
      well as downstream by controlling p53 stability via Mdm2 expression.

PMID- 14570893
TI  - RNA interference-mediated silencing of the S100A10 gene attenuates plasmin
      generation and invasiveness of Colo 222 colorectal cancer cells.
AB  - S100A10 is a key plasminogen receptor of the extracellular cell surface that is
      overexpressed in many cancer cells. Typically, S100A10 is thought to be anchored
      to the plasma membrane via the phospholipid-binding sites of its binding partner,
      annexin A2. Here, using the potent and highly sequence-specific mechanism of RNA
      interference (RNAi), we have stably silenced the expression of the S100A10 gene
      in colorectal (CCL-222) cancer cells. We show that siRNA expression mediated by
      the pSUPER vector causes efficient, stable, and specific down-regulation of
      S100A10 gene expression. The siRNA-mediated down-regulation of S100A10 gene
      expression resulted in a major decrease in the appearance of extracellular
      S100A10 protein and correlated with a 45% loss of plasminogen binding, a 65% loss
      in cellular plasmin generation and a complete loss in plasminogen-dependent
      cellular invasiveness. We also observed that the CCL-222 cells do not express
      annexin A2 on their extracellular surface. Thus, the data show that annexin A2 is
      not required by S100A10 for its association with the plasma membrane, for its
      colocalization with uPAR, or for its binding and activation of plasminogen.

PMID- 14570894
TI  - Identification of residues crucially involved in the binding of the heme moiety
      of soluble guanylate cyclase.
AB  - Soluble guanylate cyclase (sGC), a heterodimeric hemeprotein, is the only
      receptor for the biological messenger nitric oxide (NO) identified to date and is
      intimately involved in various signal transduction pathways. By using the
      recently discovered NO- and heme-independent sGC activator BAY 58-2667 and a
      novel cGMP reporter cell, we could distinguish between heme-containing and heme
      free sGC in an intact cellular system. Using these novel tools, we identified the
      invariant amino acids tyrosine 135 and arginine 139 of the beta(1)-subunit as
      crucially important for both the binding of the heme moiety and the activation of
      sGC by BAY 58-2667. The heme is displaced by BAY 58-2667 due to a competition
      between the carboxylic groups of this compound and the heme propionic acids for
      the identified residues tyrosine 135 and arginine 139. This displacement results
      in the release of the axial heme ligand histidine 105 and to the observed
      activation of sGC. Based on these findings we postulate a signal transmission
      triad composed of histidine 105, tyrosine 135, and arginine 139 responsible for
      the enzyme activation by this compound and probably also for transducing changes
      in heme status and porphyrin geometry upon NO binding into alterations of sGC
      catalytic activity.

PMID- 14570895
TI  - High resolution X-ray structure of dTDP-glucose 4,6-dehydratase from Streptomyces
      venezuelae.
AB  - Desosamine is a 3-(dimethylamino)-3,4,6-trideoxyhexose found in some macrolide
      antibiotics. In Streptomyces venezuelae, there are seven genes required for the
      biosynthesis of this unusual sugar. One of the genes, desIV, codes for a dTDP
      glucose 4,6-dehydratase, which is referred to as DesIV. The reaction mechanisms
      for these types of dehydratases are quite complicated with proton abstraction
      from the sugar 4'-hydroxyl group and hydride transfer to NAD+, proton abstraction
      at C-5, and elimination of the hydroxyl group at C-6 of the sugar, and finally
      return of a proton to C-5 and a hydride from NADH to C-6. Here we describe the
      cloning, overexpression, and purification, and high resolution x-ray
      crystallographic analysis to 1.44 A of wild-type DesIV complexed with dTDP.
      Additionally, for this study, a double site-directed mutant protein (D128N/E129Q)
      was prepared, crystallized as a complex with NAD+ and the substrate dTDP-glucose
      and its structure determined to 1.35 A resolution. In DesIV, the phenolate group
      of Tyr(151) and O(gamma) of Thr(127) lie at 2.7 and 2.6 A, respectively from the
      4'-hydroxyl group of the dTDP-glucose substrate. The side chain of Asp(128) is in
      the correct position to function as a general acid for proton donation to the 6'
      hydroxyl group while the side chain of Glu(129) is ideally situated to serve as
      the general base for proton abstraction at C-5. This investigation provides
      further detailed information for understanding the exquisite chemistry that
      occurs in these remarkable enzymes.

PMID- 14570896
TI  - C5a mutants are potent antagonists of the C5a receptor (CD88) and of C5L2:
      position 69 is the locus that determines agonism or antagonism.
AB  - The anaphylatoxin C5a exerts a plethora of biologic activities critical in the
      pathogenesis of systemic inflammatory diseases. Recently, we reported on a C5a
      mutant, jun/fos-A8, as a potent antagonist for the human and mouse C5a receptor
      (CD88). Addressing the molecular mechanism accounting for CD88 receptor
      antagonism by site-directed mutagenesis, we found that a positively charged amino
      acid at position 69 is crucial. Replacements by either hydrophobic or negatively
      charged amino acids switched the CD88 antagonist jun/fos-A8 to a CD88 agonist. In
      addition to CD88, the seven-transmembrane receptor C5L2 has recently been found
      to provide high affinity binding sites for C5a and its desarginated form,
      C5adesArg74. A jun/fos-A8 mutant in which the jun/ fos moieties and amino acids
      at positions 71-73 were deleted, A8Delta71-73, blocked C5a and C5adesArg74
      binding to CD88 and C5L2. In contrast, the cyclic C5a C-terminal analog peptide
      AcF-[OP-d-ChaWR] inhibited binding of the two anaphylatoxins to CD88 but not to
      C5L2, suggesting that the C5a core segment is important for high affinity binding
      to C5L2. Both receptors are coexpressed on human monocytes and the human mast
      cell line HMC-1; however, C5L2 expression on monocytes is weaker as compared with
      HMC-1 cells and highly variable. In contrast, no C5L2 expression was found on
      human neutrophils. A8Delta71-73 is the first antagonist that blocks C5a and
      C5adesArg74 binding to both C5a receptors, CD88 and C5L2, making it a valuable
      tool for studying C5L2 functions and for blocking the biological activities of
      C5a and C5adesArg74 in mice and humans.

PMID- 14570897
TI  - Factor Xa induces mitogenesis of vascular smooth muscle cells via autocrine
      production of epiregulin.
AB  - Factor Xa has been reported to elicit smooth muscle cell proliferation via
      autocrine release of platelet-derived growth factor. However, this study has
      shown that factor Xa-induced mitogenesis of rat aortic smooth muscle cell is
      independent of platelet-derived growth factor. We also could not observe any
      platelet-derived growth factor isoforms in the cultured medium of factor Xa
      stimulated cells. Our finding that the cultured medium of factor Xa-stimulated
      cells strongly induces rat aortic smooth muscle cell mitogenesis in the absence
      of factor Xa activity led us to explore the existence of a novel autocrine
      pathway. The autocrine growth factor was purified from the cultured medium and
      was identified to be epiregulin. Recombinant epiregulin was also able to induce
      the mitogenesis. The secretion of epiregulin from factor Xa-stimulated rat aortic
      smooth muscle cell required mRNA expression and protein synthesis of the growth
      factor. The mitogenic effect of factor Xa on rat aortic smooth muscle cell was
      significantly reduced by anti-epiregulin antibody or by antisense
      oligodeoxynucleotide to epiregulin. Several lines of experimental evidence
      clearly indicate that the autocrine production of epiregulin, an epidermal growth
      factor-related ligand, is induced in the factor Xa-stimulated mitogenic process
      of rat aortic smooth muscle cell.

PMID- 14570898
TI  - Genomic structure of human OKL38 gene and its differential expression in kidney
      carcinogenesis.
AB  - We previously demonstrated the growth inhibitory property of OKL38 and its
      possible roles in mammary carcinogenesis. To further understand the regulation
      and roles of OKL38 in tumorigenesis we proceeded to clone and characterize the
      human OKL38 gene and three of its variants with transcripts of 1.9, 2.2, and 2.4
      kb. The human OKL38 gene spans approximately 18 kb and contains 8 exons and 7
      introns with exon size ranging from 92 to 1270 bp. RT-PCR and sequence analysis
      suggest that different transcripts were arrived through differential promoter
      usage and alternate splicing. Multiple Tissue Expression array (MTE) and Multiple
      Tissue Northern blot (MTN) indicated that OKL38 was ubiquitously expressed in all
      tissues with high expression in liver, kidney, and testis. The cancer profiling
      array (CPA) of paired normal/tumor cDNA showed that OKL38 mRNA was down-regulated
      in 70% (14 of 20) of kidney tumors. Western analysis revealed that the OKL38
      protein was undetectable in 78% (7 of 9 pairs) of kidney tumor tissues.
      Immunohistological analysis showed that 64% (14 of 22) of kidney tumors were
      either lost or underexpressed OKL38 protein compared with the adjacent normal
      tissue. A transfection study using OKL38-eGFP recombinant construct showed that
      overexpression of the 52 kDa OKL38 protein in A498 cells resulted in growth
      inhibition and cell death. This study demonstrates the complex genomic structure
      of the OKL38 gene and its growth inhibitory and cytotoxic properties. Our data
      suggest the potential use of OKL38 in diagnosis, prognosis, and/or treatment of
      kidney cancer.

PMID- 14570899
TI  - Acute regulation of Na/H exchanger NHE3 by adenosine A(1) receptors is mediated
      by calcineurin homologous protein.
AB  - Adenosine is an autacoid that regulates renal Na(+) transport. Activation of
      adenosine A(1) receptor (A(1)R) by N(6)-cyclopentidyladenosine (CPA) inhibits the
      Na(+)/H(+) exchanger 3 (NHE3) via phospholipase C/Ca(2+)/protein kinase C (PKC)
      signaling pathway. Mutation of PKC phosphorylation sites on NHE3 does not
      affected regulation of NHE3 by CPA, but amino acid residues 462 and 552 are
      essential for A(1)R-dependent control of NHE3 activity. One binding partner of
      the NHE family is calcineurin homologous protein (CHP). We tested the role of
      NHE3-CHP interaction in mediating CPA-induced inhibition of NHE3 in opossum
      kidney (OK) and Xenopus laevis uroepithelial (A6) cells. Both native and
      transfected NHE3 and CHP are present in the same immuno-complex by co
      immunoprecipitation. CPA (10(-6) M) increases CHP-NHE3 interaction by 30 - 60%
      (native and transfected proteins). Direct CHP-NHE3 interaction is evident by
      yeast two-hybrid assay (bait, NHE3(C terminus); prey, CHP); the minimal
      interacting region is localized to the juxtamembrane region of NHE3(C terminus)
      (amino acids 462-552 of opossum NHE3). The yeast data were confirmed in OK cells
      where truncated NHE3 (NHE3(delta552)) still shows CPA-stimulated CHP interaction.
      Overexpression of the polypeptide from the CHP binding region (NHE3(462-552))
      interferes with the ability of CPA to inhibit NHE3 activity and to increase
      CHPNHE3(Full-length) interaction. Reduction of native CHP expression by small
      interference RNA abolishes the ability of CPA to inhibit NHE3 activity. We
      conclude that CHPNHE3 interaction is regulated by A(1)R activation and this
      interaction is a necessary and integral part of the signaling pathway between
      adenosine and NHE3.

PMID- 14570900
TI  - Minihelix-containing RNAs mediate exportin-5-dependent nuclear export of the
      double-stranded RNA-binding protein ILF3.
AB  - The karyopherin-related nuclear transport factor exportin-5 preferentially
      recognizes and transports RNAs containing minihelix motif, a structural cis
      acting export element that comprises a double-stranded stem (>14 nucleotides)
      with a base-paired 5' end and a 3-8-nucleotide protruding 3' end. This structural
      motif is present in various small cellular and viral polymerase III transcripts
      such as the adenovirus VA1 RNA (VA1). Here we show that the double-stranded RNA
      binding protein, ILF3 (interleukin enhancer binding factor 3) preferentially
      binds minihelix motif. Gel retardation assays and glutathione S-transferase pull
      down experiments revealed that ILF3, exportin-5, RanGTP, and VA1 RNA assembled in
      a quaternary complex in which the RNA moiety bridges the interaction between ILF3
      and exportin-5. Formation of this complex is facilitated by the ability of both
      exportin-5 and ILF3 to mutually increase their apparent affinity for VA1 RNA.
      Using microinjection in the nucleus of HeLa cells and transfection experiments,
      we show here that formation of the cooperative RanGTP-dependent RNA/ILF3/exportin
      5 complex promotes the co-transport of VA1 and ILF3 from the nucleus to the
      cytoplasm. Exportin-5 thus appears as the first example of a nuclear export
      receptor that mediates RNA export but also promotes transport of proteinaceous
      cargo through appropriate and specific RNA adaptors.

PMID- 14570901
TI  - Glutamine stimulates argininosuccinate synthetase gene expression through
      cytosolic O-glycosylation of Sp1 in Caco-2 cells.
AB  - Glutamine stimulates the expression of the argininosuccinate synthetase (ASS)
      gene at both the level of enzyme activity and mRNA in Caco-2 cells. Searching to
      identify the pathway involved, we observed that (i) the stimulating effect of
      glutamine was totally mimicked by glucosamine addition, and (ii) its effect but
      not that of glucosamine was totally blocked by 6-diazo-5-oxo-l-norleucine (DON),
      an inhibitor of amidotransferases, suggesting that the metabolism of glutamine to
      glucosamine 6-phosphate was required. Moreover, run-on assays revealed that
      glucosamine was acting at a transcriptional level. Because three functional GC
      boxes were identified on the ASS gene promoter (Anderson, G. M., and Freytag, S.
      O. (1991) Mol. Cell Biol. 11, 1935-1943), the potential involvement of Sp1 family
      members was studied. Electrophoretic mobility shift assays using either the Sp1
      consensus sequence or an appropriate fragment of the ASS promoter sequence as a
      probe demonstrated that both glutamine and glucosamine increased Sp1 DNA binding.
      Immunoprecipitation-Western blot experiments demonstrated that both compounds
      increased O-glycosylation of Sp1 leading to its translocation into nucleus.
      Again, the effect of glutamine on Sp1 was inhibited by the addition of DON but
      not of glucosamine. Taken together, the results clearly demonstrate that the
      metabolism of glutamine through the hexosamine pathway leads to the cytosolic O
      glycosylation of Sp1, which, in turn, translocates into nucleus and stimulates
      the ASS gene transcription. Collectively, the results constitute the first
      demonstration of a functional relationship between a regulating signal
      (glutamine), a transcription factor (Sp1), and the transcription of the ASS gene.

PMID- 14570902
TI  - Phospholipase activity of phospholipase C-gamma1 is required for nerve growth
      factor-regulated MAP kinase signaling cascade in PC12 cells.
AB  - Phospholipase C-gamma1 (PLC-gamma1) hydrolyzes phosphatidylinositol 4,5
      bisphosphate to the second messengers inositol 1,4,5-trisphosphate and
      diacylglycerol (DAG). PLC-gamma1 is implicated in a variety of cellular
      signalings and processes including mitogenesis and calcium entry. However,
      numerous studies demonstrate that the lipase activity is not required for PLC
      gamma1 to mediate these events. Here, we report that the phospholipase activity
      of PLC-gamma1 plays an essential role in nerve growth factor (NGF)-triggered
      Raf/MEK/MAPK pathway activation in PC12 cells. Employing PC12 cells stably
      transfected with an inducible form of wild-type PLC-gamma1 or lipase inactive PLC
      gamma1 with histidine 335 mutated into glutamine in the catalytic domain, we show
      that NGF provokes robust activation of MAP kinase in wild-type but not in lipase
      inactive cells. Both Ras/C-Raf/MEK1 and Rap1/B-Raf/MEK1 pathways are intact in
      the wild-type cells. By contrast, these signaling cascades are diminished in the
      mutant cells. Pretreatment with cell permeable DAG analog 1-oleyl-2
      acetylglycerol rescues the MAP kinase pathway activation in the mutant cells.
      These observations indicate that the lipase activity of PLC-gamma1 mediates NGF
      regulated MAPK signaling upstream of Ras/Rap1 activation probably through second
      messenger DAG-activated Ras and Rap-GEFs.

PMID- 14570903
TI  - Sequence-based design of kinase inhibitors applicable for therapeutics and target
      identification.
AB  - A platform for specifically modulating kinase-dependent signaling using peptides
      derived from the catalytic domain of the kinase is presented. This technology,
      termed KinAce, utilizes the canonical structure of protein kinases. The targeted
      regions (subdomain V and subdomains IX and X) are analyzed and their sequence,
      three-dimensional structure, and involvement in protein-protein interaction are
      highlighted. Short myristoylated peptides were derived from the target regions of
      the tyrosine kinases c-Kit and Lyn and the serine/threonine kinases 3
      phosphoinositide-dependent kinase-1 (PDK1) and Akt/protein kinase B (PKB). For
      each kinase an active designer peptide is shown to selectively inhibit the
      signaling of the kinase from which it is derived, and to inhibit cancer cell
      proliferation in the micromolar range. This technology emerges as an applicable
      tool for deriving sequence-based selective inhibitors for a broad range of
      protein kinases as hits that may be further developed into drugs. Moreover, it
      enables identification of novel kinase targets for selected therapeutic
      indications as demonstrated in the KinScreen application.

PMID- 14570904
TI  - Suppression of adriamycin-induced apoptosis by sustained activation of the
      phosphatidylinositol-3'-OH kinase-Akt pathway.
AB  - The mechanisms by which growth factors trigger signal transduction pathways
      leading to protection against apoptosis are of great interest. In this study, we
      investigated the effect of hepatocyte growth factor (HGF/SF) and epidermal growth
      factor (EGF) on adriamycin (ADR)-induced apoptosis. Treatment of human epithelial
      MKN74 cells with ADR, a DNA topoisomerase IIalpha inhibitor, caused apoptosis.
      However, cells pretreated with HGF/SF, but not those pretreated with EGF, were
      resistant to this apoptosis. The protective effect of HGF/SF against the ADR
      induced apoptosis was abolished in the presence of either LY294002, an inhibitor
      of phosphatidylinositol-3'-OH kinase (PI3-K) or 1L-6-hydroxymethyl-chiro-inositol
      2-(R)-2-O-methyl-3-O-octadecylcarbonate, an inhibitor of Akt, thus implicating
      the activation of PI3-K-Akt signaling in the antiapoptotic action of HGF/SF.
      Immunoblotting analysis revealed that HGF/SF stimulated the sustained
      phosphorylation of Akt for several hours but that EGF stimulated the
      phosphorylation only transiently. Furthermore, ADR-induced activation of caspase
      9, a downstream molecule of Akt, was inhibited for at least 24 h after HGF/SF
      stimulation, but it was not affected by EGF stimulation. Cell-surface biotin
      labeling analysis showed that the HGF/SF receptor remained on the cell surface
      until at least 30 min after HGF/SF addition but that the EGF receptor level on
      the cell surface was attenuated at an earlier time after EGF addition. These
      results indicate that HGF/SF, but not EGF, transmitted protective signals against
      ADR-induced apoptosis by causing sustained activation of the PI3-K-Akt signaling
      pathway. Furthermore, the difference in antiapoptotic capacity between HGF/SF and
      EGF is explained, at least in part, by the delayed down-regulation of the HGF/SF
      receptor.

PMID- 14570905
TI  - Spatio-temporal regulation of Rac1 and Cdc42 activity during nerve growth factor
      induced neurite outgrowth in PC12 cells.
AB  - Neurite outgrowth is an important process in the formation of neuronal networks.
      It is widely accepted that Rac1 and Cdc42, members of the Rho GTPase family,
      positively regulate neurite extension through reorganization of the actin
      cytoskeleton; however, it remains largely unknown when and where Rac1 and Cdc42
      are activated during neuritogenesis. This study visualized the spatio-temporal
      regulation of Rac1 and Cdc42 activities during nerve growth factor (NGF)-induced
      neurite outgrowth in living PC12 cells by using probes based on the principle of
      fluorescence resonance energy transfer (FRET). Immediately after the addition of
      NGF, Rac1 and Cdc42 were transiently activated in broad areas of the cell
      periphery; a repetitive activation and inactivation cycle was then observed at
      the motile tips of protrusions. This localized activation, which was more evident
      in PC12 cells treated with NGF for more than 24 h, might facilitate neurite
      extension, because the expression of constitutively active mutants of Rac1 and
      Cdc42 abrogated NGF-induced neurite outgrowth. FRET imaging also delineated a
      difference between the localization of activated Rac1 and that of Cdc42 within
      the neurite tips. Experiments with dominant-negative mutants suggested that Rac1
      and Cdc42 were activated by a common guanine nucleotide exchange factor(s) in an
      early stage of the activation phase. Therefore, the difference between Rac1- and
      Cdc42-activated areas possibly came from the differential localization between
      Rac1-specific GTPase-activation proteins (GAPs) and Cdc42-specific GAPs. It was
      concluded that the localized activation of Rac1 and Cdc42 was caused by both
      guanine nucleotide exchange factors and GAPs, and was important for neurite
      extension.

PMID- 14570906
TI  - CD4 receptor localized to non-raft membrane microdomains supports HIV-1 entry.
      Identification of a novel raft localization marker in CD4.
AB  - Despite the preferential localization of CD4 to lipid rafts, the significance and
      role of these microdomains in HIV-1 entry is still controversial. The possibility
      that CD4, when localized to non-raft domains, might be able to support virus
      entry cannot be excluded. Because disintegration of rafts by extraction of
      cellular cholesterol with methyl-beta-cyclodextrin suffers from various adverse
      effects, we investigated molecular determinants controlling raft localization of
      the CD4 receptor. Extensive mutagenesis of the receptor showed that a raft
      localizing marker, consisting of a short sequence of positively charged amino
      acid residues, RHRRR, was present in the membrane-proximal cytoplasmic domain of
      CD4. Substitution of the RHRRR sequence with alanine residues abolished raft
      localization of the CD4 mutant, RA5, as determined biochemically using
      solubilization in nonionic detergents and by confocal microscopy. The possible
      inhibitory effect of the introduced mutations on the adjacent CVRC palmitoylation
      site was ruled out because wild type (wt) CD4 and RA5, but not a palmitoylation
      deficient mutant, were efficiently palmitoylated. Nonetheless, the RA5 mutant
      supported productive virus entry to levels equivalent to that of wild type (wt)
      CD4. Sucrose gradient analysis of Triton X-100 virus lysates showed that Gag and
      envelope gp120 proteins accumulated in low buoyant, high-density fractions. This
      pattern was changed after virus incubation with cells. Whereas Gag proteins
      localized to lipid rafts in cells expressing wt CD4 and RA5, gp120 accumulated in
      rafts in cells expressing wt CD4 but not RA5. We propose that raft localization
      of CD4 is not required for virus entry, however, post-binding fusion/entry steps
      may require lipid raft assembly.

PMID- 14570907
TI  - Cysteine string protein (CSP) inhibition of N-type calcium channels is blocked by
      mutant huntingtin.
AB  - Cysteine string protein (CSP), a 34-kDa molecular chaperone, is expressed on
      synaptic vesicles in neurons and on secretory vesicles in endocrine,
      neuroendocrine, and exocrine cells. CSP can be found in a complex with two other
      chaperones, the heat shock cognate protein Hsc70, and small glutamine-rich
      tetratricopeptide repeat domain protein (SGT). CSP function is vital in synaptic
      transmission; however, the precise nature of its role remains controversial. We
      have previously reported interactions of CSP with both heterotrimeric GTP-binding
      proteins (G proteins) and N-type calcium channels. These associations give rise
      to a tonic G protein inhibition of the channels. Here we have examined the
      effects of huntingtin fragments (exon 1) with (huntingtin(exon1/exp)) and without
      (huntingtin(exon1/nonexp)) expanded polyglutamine (polyQ) tracts on the CSP
      chaperone system. In vitro huntingtin(exon1/exp) sequestered CSP and blocked the
      association of CSP with G proteins. In contrast, huntingtin(exon1/nonexp) did not
      interact with CSP and did not alter the CSP/G protein association. Similarly, co
      expression of huntingtin(exon1/exp) with CSP and N-type calcium channels
      eliminated CSP's tonic G protein inhibition of the channels, while coexpression
      of huntingtin(exon1/nonexp) did not alter the robust inhibition promoted by CSP.
      These results indicate that CSP's modulation of G protein inhibition of calcium
      channel activity is blocked in the presence of a huntingtin fragment with
      expanded polyglutamine tracts.

PMID- 14570908
TI  - An apoptotic signaling pathway in the interferon antiviral response mediated by
      RNase L and c-Jun NH2-terminal kinase.
AB  - Cellular stress responses induced during viral infections are critical to the
      health and survival of organisms. In higher vertebrates, interferons (IFNs)
      mediate the innate antiviral response in part through the action of RNase L, a
      uniquely regulated enzyme. RNase L is activated by 5'-phosphorylated, 2'-5'
      oligoadenylates (2-5A) produced from IFN-inducible and double stranded RNA
      dependent synthetases. We show that viral activation of the c-Jun NH2-terminal
      kinases (JNK) family of MAP kinases and viral induction of apoptosis are both
      deficient in mouse cells lacking RNase L. Also, JNK phosphorylation in response
      to 2-5A was greatly reduced in RNase L-/- mouse cells. In addition, 2-5A
      treatment of the human ovarian carcinoma cell line, Hey1b, resulted in specific
      ribosomal RNA cleavage products coinciding with JNK activation. Furthermore,
      suppression of JNK activity with the chemical inhibitor, SP600125, prevented
      apoptosis induced by 2-5A. In contrast, inhibition of alternative MAP kinases,
      p38 and ERK, failed to prevent 2-5A-mediated apoptosis. Short interfering RNA to
      JNK1/JNK2 mRNAs resulted in JNK ablation while also suppressing 2-5A-mediated
      apoptosis. Moreover, Jnk1-/- Jnk2-/- cells were highly resistant to the apoptotic
      effects of IFN and 2-5A. These findings suggest that JNK and RNase L function in
      an integrated signaling pathway during the IFN response that leads to elimination
      of virus-infected cells through apoptosis.

PMID- 14570909
TI  - Unlike Diablo/smac, Grim promotes global ubiquitination and specific degradation
      of X chromosome-linked inhibitor of apoptosis (XIAP) and neither cause apoptosis.
AB  - Grim is a Drosophila inhibitor of apoptosis (IAP) antagonist that directly
      interferes with inhibition of caspases by IAPs. Expression of Grim, or removal of
      DIAP1, is sufficient to activate apoptosis in fly cells. Transient expression of
      Grim in mammalian cells induces apoptosis, arguing for the conservation of
      apoptotic pathways, but cytoplasmic expression of the mammalian IAP antagonist
      Diablo/smac does not. To understand why, we compared Grim and Diablo. Although
      they have the same IAP binding specificity, only Grim promoted XIAP
      ubiquitination and degradation. Grim also synergized with XIAP to promote an
      increase in total cellular ubiquitination, whereas Diablo antagonized this
      activity. Surprisingly, Grim-induced ubiquitination of XIAP did not require the
      IAP RING finger. Analysis of a Grim mutant that promoted XIAP degradation, but
      was not cytotoxic, suggests that Grim killing in transient assays is due to a
      combination of IAP depletion, blocking of IAP-mediated caspase inhibition, and at
      least one other unidentified function. Unlike transiently transfected cells,
      inducible mammalian cell lines can sustain continuous expression of Grim and
      selective degradation of XIAP without undergoing apoptosis, demonstrating that
      down-regulation and antagonism of IAPs is not sufficient to cause apoptosis of
      mammalian cells.

PMID- 14570910
TI  - Specific interaction with transcription factor IIA and localization of the
      mammalian TATA-binding protein-like protein (TLP/TRF2/TLF).
AB  - TBP-like protein (TLP) is structurally similar to the TATA-binding protein (TBP)
      and is thought to have a transcriptional regulation function. Although TLP has
      been found to form a complex with transcription factor IIA (TFIIA), the in vivo
      functions of TFIIA for TLP are not clear. In this study, we analyzed the
      interaction between TLP and TFIIA. We determined the biophysical properties for
      the interaction of TLP with TFIIA. Dissociation constants of TFIIA versus TLP and
      TFIIA versus TBP were 1.5 and 10 nm, respectively. Moreover, the dissociation
      rate constant of TLP and TFIIA (1.2 x 10(-4)/m.s was significantly lower than
      that of TBP (2.1 x 10(-3)/m.s). These results indicate that TLP has a higher
      affinity to TFIIA than does TBP and that the TLP-TFIIA complex is much more
      stable than is the TBP-TFIIA complex. We found that TLP forms a dimer and a
      trimer and that these multimerizations are inhibited by TFIIA. Moreover, TLP
      mutimers were more stable than a TBP dimer. We determined the amounts of TLPs in
      the nucleus and cytoplasm of NIH3T3 cells and found that the molecular number of
      TLP in the nucleus was only 4% of that in the cytoplasm. Immunostaining of cells
      also revealed cytoplasmic localization of TLP. We established cells that stably
      express mutant TLP lacking TFIIA binding ability and identified the amino acids
      of TLP required for TFIIA binding (Ala-32, Leu-33, Asn-37, Arg-52, Lys-53, Lys
      78, and Arg-86). Interestingly, the level of TFIIA binding defective mutant TLPs
      in the nucleus was much higher than that of the wild-type TLP and TFIIA
      interactable mutant TLPs. Immunostaining analyses showed consistent results.
      These results suggest that the TFIIA binding ability of TLP is required for
      characteristic cytoplasmic localization of TLP. TFIIA may regulate the
      intracellular molecular state and the function of TLP through its property of
      binding to TLP.

PMID- 14570911
TI  - A novel AP-1 site is critical for maximal induction of the follicle-stimulating
      hormone beta gene by gonadotropin-releasing hormone.
AB  - Regulation of follicle-stimulating hormone (FSH) synthesis is a central point of
      convergence for signals controlling reproduction. The FSHbeta subunit is
      primarily regulated by gonadotropin-releasing hormone (GnRH), gonadal steroids,
      and activin. Here, we identify elements in the mouse FSHbeta promoter responsible
      for GnRH-mediated induction utilizing the LbetaT2 cell line that endogenously
      expresses FSH. The proximal 398 bp of the mouse FSHbeta promoter is sufficient
      for response to GnRH. This response localizes primarily to an AP-1 half-site (
      72/-69) juxtaposed to a CCAAT box, which binds nuclear factor-Y. Both elements
      are required for AP-1 binding, creating a novel AP-1 site. Multimers of this site
      confer GnRH induction, and mutation or internal deletion of this site reduces
      GnRH induction by 35%. The same reduction was achieved using a dominant negative
      Fos protein. This is the only functional AP-1 site identified in the proximal 398
      bp, since its mutation eliminates FSHbeta induction by c-Fos and c-Jun. GnRH
      regulation of the FSHbeta gene occurs through induction of multiple Fos and Jun
      isoforms, forming at least four different AP-1 molecules, all of which bind to
      this site. Mitogen-activated protein kinase activity is required for induction of
      FSHbeta and JunB protein. Finally, AP-1 interacts with nuclear factor-Y, which
      occupies its overlapping site in vivo.

PMID- 14570913
TI  - An essential role of Sam50 in the protein sorting and assembly machinery of the
      mitochondrial outer membrane.
AB  - The preprotein translocase of the outer mitochondrial membrane (TOM complex)
      contains one essential subunit, the channel Tom40. The assembly pathway of the
      precursor of Tom40 involves the TOM complex and the sorting and assembly
      machinery (SAM complex) with the non-essential subunit Mas37. We have identified
      Sam50, the second essential protein of the mitochondrial outer membrane. Sam50
      contains a beta-barrel domain conserved from bacteria to man and is a subunit of
      the SAM complex. Yeast mutants of Sam50 are defective in the assembly pathways of
      Tom40 and the abundant outer membrane protein porin, while the import of matrix
      proteins is not affected. Thus the protein sorting and assembly machinery of the
      mitochondrial outer membrane involves an essential, conserved protein.

PMID- 14570912
TI  - Erythroblast transformation by FLI-1 depends upon its specific DNA binding and
      transcriptional activation properties.
AB  - FLI-1 is a transcriptional regulator of the ETS family of proteins. Insertional
      activation at the FLI-1 locus is an early event in F-murine leukemia virus
      induced erythroleukemia. Consistent with its essential role in erythroid
      transformation, enforced expression of FLI-1 in primary erythroblasts strongly
      impairs the response of these cells to erythropoietin (Epo), a cytokine essential
      to erythropoiesis. We show here that point mutations in the ETS domain that
      abolished FLI-1 binding to specific DNA elements (ETS-binding sites) suppressed
      the ability of FLI-1 to transform erythroblasts. The exchange of the entire ETS
      domain (DNA binding domain) of FLI-1 for that of PU.1 changed the DNA binding
      specificity of FLI-1 for that of PU.1 and impaired FLI-1 transforming properties.
      In contrast, ETS domain swapping mutants that maintained the DNA binding
      specificity of FLI-1 did not affect the ability of FLI-1 to transform
      erythroblasts. Deletion and swapping mutants that failed to inhibit the DNA
      binding activity of FLI-1 but impaired its transcriptional activation properties
      were also transformation-defective. Taken together, these results show that both
      the ability of FLI-1 to inhibit Epo-induced differentiation of erythroblasts and
      to confer enhanced cell survival in the absence of Epo critically depend upon FLI
      1 ETS-binding site-dependent transcriptional activation properties.

PMID- 14570914
TI  - Caspase 3-mediated proteolysis of the N-terminal cytoplasmic domain of the human
      erythroid anion exchanger 1 (band 3).
AB  - The N-terminal cytoplasmic domain of the anion exchanger 1 (AE1 or band 3) of the
      human erythrocyte associates with peripheral membrane proteins to regulate
      membrane-cytoskeleton interactions, with glycolytic enzymes such as
      glyceraldehyde-3-phosphate dehydrogenase and aldolase, with the protein-tyrosine
      kinase p72syk, with hemoglobin and with hemichromes. We have demonstrated that
      the N-terminal cytoplasmic domain of band 3 (CDB3) is a substrate of the
      apoptosis executioner caspase 3 (1). CDB3 has two non-conventional caspase 3
      cleavage sites, TATD45 and EQGD205 (2). In vitro treatment of recombinant CDB3
      with caspase 3 generated two fragments, which could be blocked by pretreatment
      with the caspase 3 inhibitor Z-DEVD-fmk (3). Recombinant CDB3 in which the
      caspase 3 cleavage sites Asp45 and Asp205 were mutated, was resistant to
      proteolysis (4). Proteolytically derived fragments crossreactive with polyclonal
      anti-band 3 antibody appeared with simultaneous cleavage of poly (ADP-ribose)
      polymerase and procaspase 3 in staurosporine (STS)-treated HEK293 cells
      transiently transfected with CDB3 (5). In vivo cleavage of CDB3 could be blocked
      by pretreatment of cells with Z-DEVD-fmk or in cells transfected with mutant CDB3
      (D45A, D205A) (6). Co-transfection experiments showed that STS-mediated cleavage
      of CDB3 diminished its interaction with the N-terminal domain of protein 4.2,
      confirming that such cleavage interferes with the interaction of CDB3 with
      cytoskeletal proteins (7). Active caspase 3 was observed in aged red cells but
      not in young cells. This red cell caspase 3 could cleave band 3 present in inside
      out vesicles prepared from young erythrocytes arguing in favor of a physiological
      role of caspase 3 in aged erythrocytes.

PMID- 14570915
TI  - Modulation of mature cystic fibrosis transmembrane regulator protein by the PDZ
      domain protein CAL.
AB  - We have previously identified the cystic fibrosis transmembrane regulator (CFTR)
      interacting protein CAL and demonstrated that CAL modulates CFTR plasma membrane
      expression by retaining CFTR within the cell. Here, we report that in addition to
      regulating membrane expression, CAL also regulates the expression of mature CFTR.
      The co-expression of hemagglutinin-tagged or Myc-tagged CAL with green
      fluorescent protein (GFP)-CFTR in COS-7 cells causes a dose-dependent reduction
      in mature GFP-CFTR, independent of its tags. Bafilomycin A1, a lysosomal proton
      pump inhibitor, increases mature GFP-CFTR, confirming previous reports of
      lysosomal degradation of mature CFTR. Importantly, bafilomycin A1 reverses CAL
      mediated CFTR degradation. The proteasome inhibitor, MG132, on the other hand,
      does not reverse the effect of CAL. CAL has no effect on CFTR maturation,
      suggesting that it exerts its effects on mature CFTR. Co-expression of CAL
      enhances the degradation of CFTR. We showed previously that CAL reduces the half
      life of CFTR at the cell surface. Here we show that expression of dominant
      negative dynamin 2 K44A, a large GTPase inhibitor that is known to inhibit
      clathrin-mediated endocytosis and vesicle formation in the Golgi, increases cell
      surface CFTR as measured by surface biotinylation. More importantly, dynamin 2
      K44A also restores cell surface CFTR in CAL-overexpressing cells and partially
      blocks the CAL-mediated degradation of mature CFTR. These data suggest a model in
      which CAL retains CFTR in the cell and targets CFTR for degradation.

PMID- 14570916
TI  - The Ku antigen-recombination signal-binding protein Jkappa complex binds to the
      nuclear factor-kappaB p50 promoter and acts as a positive regulator of p50
      expression in human gastric cancer cells.
AB  - The p50 subunit of NF-kappaB is a transcription factor that regulates the
      expression of a variety of genes. Previously, we showed that the expression of Ku
      antigen, a DNA repair protein, is mediated by NF-kappaB in gastric cancer AGS
      cells (Lim, J. W., Kim, H., and Kim, K. H. (2002) J. Biol. Chem. 277, 46093
      46100). In this study, we report that the inhibition of Ku activity reduced both
      p50 expression and nuclear NF-kappaB activity in AGS cells. A co
      immunoprecipitation experiment demonstrated that Ku antigen interacted with
      recombination signal-binding protein Jkappa (RBP-Jkappa), a DNA-binding protein.
      Ku antigen, RBP-Jkappa, and p50 were found to bind to the DNA region containing
      the kappaB element in the p50 promoter. Supershift and competition experiments
      demonstrated that Ku antigen and RBP-Jkappa bound sequence-specifically to
      downstream elements of kappaB at GCTTC and TGGGGG. mRNA expression and de novo
      synthesis of p50 were inhibited in cells transfected with the mutant gene
      expression constructs for IkappaBalpha, Ku80, and RBP-Jkappa. A reporter assay
      demonstrated that p50 transcription was positively mediated by NF-kappaB, Ku
      antigen, and RBP-Jkappa and that the binding elements for these proteins were
      required for optimal p50 expression. The interaction of Ku antigen with RBP
      Jkappa and NF-kappaB p50 may act as a positive regulator of p50 expression in
      gastric cancer AGS cells.

PMID- 14570917
TI  - pH regulates vascular endothelial growth factor binding to fibronectin: a
      mechanism for control of extracellular matrix storage and release.
AB  - Hypoxia is one of the major signals that induces angiogenesis. Hypoxic conditions
      lead to reduced extracellular pH. Vascular endothelial growth factor (VEGF)
      binding to endothelial cells and the extracellular matrix (ECM) increases at
      acidic pH (7.0-5.5). These interactions are dependent on heparan sulfate
      proteoglycans, but do not depend on the presence of VEGF receptors. Here we
      report that VEGF(165) and VEGF(121) binding to fibronectin also increased at
      acidic pH, and that these interactions are further enhanced by the addition of
      heparin. These results reveal that the accepted non-heparin-binding isoform of
      VEGF (VEGF(121)) is converted into a heparin-binding growth factor under acidic
      conditions. Interestingly, we did not observe increased binding of VEGF to
      collagen type I at acidic pH in the presence or absence of heparin, indicating
      that this effect is not a general property of all heparin-binding ECM proteins.
      The high level of VEGF binding at acidic pH was also rapidly reversed as
      demonstrated by increased rates of VEGF dissociation from fibronectin and
      fibronectin-heparin matrices as the pH was raised. The VEGF released from
      fibronectin retained its ability to stimulate the activation of extracellular
      regulated kinase 1/2 in endothelial cells. These results suggest that VEGF may be
      stored in the extracellular matrix via interactions with fibronectin and heparan
      sulfate in tissues that are in need of vascularization so that it can aid in
      directing the dynamic process of growth and migration of new blood vessels.

PMID- 14570919
TI  - The effects of glucose concentration on the reciprocal regulation of rRNA
      promoters in Plasmodium falciparum.
AB  - The developmental progression of Plasmodium falciparum is remarkably sensitive to
      glucose concentration. We have investigated the effects of glucose concentration
      on the parasite development cycle as reflected by changes of ribosomal RNA (rRNA)
      transcription. We showed that glucose starvation differentially affects
      transcriptional control of the rRNA genes by sharply repressing transcription
      from those loci involved with asexual development of the parasite while up
      regulating transcription at those loci involved with sexual development of the
      parasite. Temperature change also effects regulation of transcription. We found
      that the effects of temperature and glucose were synergistic. We identified and
      compared the upstream region of the transcription start sites of each gene. These
      putative promoter structures are considerably different from one another and
      contain structures remarkably similar to rRNA control elements in other
      organisms.

PMID- 14570918
TI  - Cys32 and His105 are the critical residues for the calcium-dependent cysteine
      proteolytic activity of CvaB, an ATP-binding cassette transporter.
AB  - CvaB, a member of the ATP-binding cassette transporter superfamily, is the
      central membrane transporter of the colicin V secretion system in Escherichia
      coli. Cys32 and His105 in the N-terminal domain of CvaB were identified as
      critical residues for both colicin V secretion and cysteine proteolytic activity.
      By inhibiting degradation with N-ethylmaleimide and a mixture of protease
      inhibitors, a stable wild-type N-terminal domain (which showed cysteine protease
      activity when activated) was purified. Such protease activity was Ca2+- and
      concentration-dependent and could be inhibited by antipain, N-ethylmaleimide,
      EDTA, and EGTA. At low concentrations, the Ca2+ analogs Tb3+ and La3+ (but not
      Fe3+) significantly enhanced proteolytic activity, suggesting that the size of
      the cations is important for activity. Together with comparisons of the sequences
      of members of the cysteine protease family, these results indicate that Cys32 and
      His105 are the critical residues in the CvaB N-terminal domain for the calcium
      dependent cysteine protease activity and secretion of colicin V.

PMID- 14570920
TI  - The co-repressor hairless protects RORalpha orphan nuclear receptor from
      proteasome-mediated degradation.
AB  - RORalpha is a constitutively active orphan nuclear receptor essential for
      cerebellar development and is previously shown to regulate genes involved in both
      myogenesis and adipogenesis. The transcriptional activity of RORalpha is
      dependent on the presence of a ubiquitous ligand and can be abolished by
      interaction with Hairless (Hr), a ligand-oblivious nuclear receptor co-repressor.
      In this study, we first demonstrate that RORalpha is a short-lived protein and
      that treatment with the MG-132 proteasome inhibitor results in the accumulation
      of ubiquitin-conjugated receptor and inhibition of transcription. These data show
      that RORalpha transcriptional activity and degradation are intrinsically linked.
      In addition, the introduction of inactivation mutations in the ligand-binding
      pocket and co-regulator-binding surface of RORalpha significantly increases
      protein stability, indicating that ligand and/or co-regulator binding perpetuates
      RORalpha degradation. Strikingly, expression of the co-repressor Hr results in
      the stabilization of RORalpha because of an inhibition of proteasome-mediated
      degradation of the receptor. Stabilization of RORalpha by Hr requires intact
      nuclear receptor recognition LXXLL motifs within Hr. Interestingly, the co
      repressor nuclear receptor co-repressor (NCoR) has no effect on RORalpha protein
      turnover. This study shows that stabilization of RORalpha is an essential
      component of Hr-mediated repression and suggests a molecular mechanism to achieve
      transcriptional repression by a liganded receptor-co-repressor complex.

PMID- 14570921
TI  - Regulation of vacuolar Na+/H+ exchange in Arabidopsis thaliana by the salt-overly
      sensitive (SOS) pathway.
AB  - For plants growing in highly saline environments, accumulation of sodium in the
      cell cytoplasm leads to disruption of metabolic processes and reduced growth.
      Maintaining low levels of cytoplasmic sodium requires the coordinate regulation
      of transport proteins on numerous cellular membranes. Our previous studies have
      linked components of the Salt-Overly-Sensitive pathway (SOS1-3) to salt tolerance
      in Arabidopsis thaliana and demonstrated that the activity of the plasma membrane
      Na+/H+ exchanger (SOS1) is regulated by SOS2 (a protein kinase) and SOS3 (a
      calcium-binding protein). Current studies were undertaken to determine if the
      Na+/H+ exchanger in the vacuolar membrane (tonoplast) of Arabidopsis is also a
      target for the SOS regulatory pathway. Characterization of tonoplast Na+/H+
      exchange demonstrated that it represents activity originating from the AtNHX
      proteins since it could be inhibited by 5-(N-methyl-N-isobutyl)amiloride and by
      anti-NHX1 antibodies. Transport activity was selective for sodium (apparent Km=31
      mm) and electroneutral (one sodium ion for each proton). When compared with
      tonoplast Na+/H+-exchange activity in wild type, activity was significantly
      higher, greatly reduced, and unchanged in sos1, sos2, and sos3, respectively.
      Activated SOS2 protein added in vitro increased tonoplast Na+/H+-exchange
      activity in vesicles isolated from sos2 but did not have any effect on activity
      in vesicles isolated from wild type, sos1, or sos3. These results demonstrate
      that (i) the tonoplast Na+/H+ exchanger in Arabidopsis is a target of the SOS
      regulatory pathway, (ii) there are branches to the SOS pathway, and (iii) there
      may be coordinate regulation of the exchangers in the tonoplast and plasma
      membrane.

PMID- 14570922
TI  - IsdG and IsdI, heme-degrading enzymes in the cytoplasm of Staphylococcus aureus.
AB  - Staphylococcus aureus requires iron for growth and utilizes heme as a source of
      iron during infection. Staphylococcal surface proteins capture hemoglobin,
      release heme from hemoglobin and transport this compound across the cell wall
      envelope and plasma membrane into the bacterial cytoplasm. Here we show that
      Staphylococcus aureus isdG and isdI encode cytoplasmic proteins with heme binding
      properties. IsdG and IsdI cleave the tetrapyrrol ring structure of heme in the
      presence of NADPH cytochrome P450 reductase, thereby releasing iron. Further,
      IsdI complements the heme utilization deficiency of a Corynebacterium ulcerans
      heme oxygenase mutant, demonstrating in vivo activity of this enzyme. Although
      Staphylococcus epidermidis, Listeria monocytogenes, and Bacillus anthracis encode
      homologues of IsdG and IsdI, these proteins are not found in other bacteria or
      mammals. Thus, it appears that bacterial pathogens evolved different strategies
      to retrieve iron from scavenged heme molecules and that staphylococcal IsdG and
      IsdI represent examples of bacterial heme-oxygenases.

PMID- 14570923
TI  - Identification of novel alternative splice variants of APOBEC-1 complementation
      factor with different capacities to support apolipoprotein B mRNA editing.
AB  - Two novel mRNA transcripts have been identified that result from species- and
      tissue-specific, alternative polyadenylation and splicing of the pre-mRNA
      encoding the apolipoprotein B (apoB) editing catalytic subunit 1 (APOBEC-1)
      complementation factor (ACF) family of related proteins. The alternatively
      processed mRNAs encode 43- and 45-kDa proteins that are components of the
      previously identified p44 cluster of apoB RNA binding, editosomal proteins.
      Recombinant ACF45 displaced ACF64 and ACF43 in mooring sequence RNA binding but
      did not demonstrate strong binding to APOBEC-1. In contrast, ACF43 bound strongly
      to APOBEC-1 but demonstrated weak binding to mooring sequence RNA. Consequently
      ACF45/43 complemented APOBEC-1 in apoB mRNA editing with less efficiency than
      full-length ACF64. These data, together with the finding that all ACF variants
      were co-expressed in rat liver nuclei (the site of apoB mRNA editing), suggested
      that ACF variants might compete with one another for APOBEC-1 and apoB mRNA
      binding and thereby contribute to the regulation of apoB mRNA editing. In support
      for this hypothesis, the ratio of nuclear ACF65/64 to ACF45/43 decreased when
      hepatic editing was inhibited by fasting and increased when editing was re
      stimulated by refeeding. These findings suggested a new model for the regulation
      of apoB mRNA editing in which the catalytic potential of editosomes is modulated
      at the level of their assembly by alterations in the relative abundance of
      multiple related RNA-binding auxiliary proteins and the expression level of
      APOBEC-1.

PMID- 14570924
TI  - A mutation in the yeast mitochondrial core RNA polymerase, Rpo41, confers defects
      in both specificity factor interaction and promoter utilization.
AB  - The yeast mitochondrial RNA polymerase (RNAP) is composed of the core RNAP,
      Rpo41, and the mitochondrial transcription factor, Mtf1. Both are required for
      mitochondrial transcription, but how the two proteins interact to create a
      functional, promoter-selective holoenzyme is still unknown. Rpo41 is similar to
      the single polypeptide bacteriophage T7RNAP, which does not require additional
      factors for promoter-selective initiation but whose activity is modulated during
      infection by association with T7 lysozyme. In this study we used the co-crystal
      structure of T7RNAP and T7 lysozyme as a model to define a potential Mtf1
      interaction surface on Rpo41, making site-directed mutations in Rpo41 at
      positions predicted to reside at the same location as the T7RNAP/T7 lysozyme
      interface. We identified Rpo41 mutant E1224A as having reduced interactions with
      Mtf1 in a two-hybrid assay and a temperature-sensitive petite phenotype in vivo.
      Although the E1224A mutant has full activity in a non-selective in vitro
      transcription assay, it is temperature-sensitive for selective transcription from
      linear DNA templates containing the 14S rRNA, COX2, and tRNAcys mitochondrial
      promoters. The tRNAcys promoter defect can be rescued by template supercoiling
      but not by addition of a dinucleotide primer. The fact that mutation of Rpo41
      results in selective transcription defects indicates that the core RNAP, like
      T7RNAP, plays an important role in promoter utilization.

PMID- 14570925
TI  - Structural control of endoplasmic reticulum-associated degradation: effect of
      chemical chaperones on 3-hydroxy-3-methylglutaryl-CoA reductase.
AB  - The endoplasmic reticulum (ER) quality control pathway destroys misfolded and
      unassembled proteins in the ER. Most substrates of this ER-associated degradation
      (ERAD) pathway are constitutively targeted for destruction through recognition of
      poorly understood structural hallmarks of misfolding. However, the normal yeast
      ER membrane protein 3-hydroxy-3-methylglutaryl-CoA reductase (Hmg2p) undergoes
      ERAD that is physiologically regulated by sterol pathway signals. We have
      proposed that Hmg2p ERAD occurs by a regulated transition to an ERAD quality
      control substrate. Consistent with this, we had previously shown that Hmg2p is
      strongly stabilized by chemical chaperones such as glycerol, which stabilize
      misfolded proteins. To understand the features of Hmg2p that permit regulated
      ERAD, we have thoroughly characterized the effects of chemical chaperones on
      Hmg2p. These agents caused a reversible, immediate, direct change in Hmg2p
      degradation consistent with an effect on Hmg2p structure. We devised an in vitro
      limited proteolysis assay of Hmg2p in its native membranes. In vitro, chemical
      chaperones caused a dramatic, rapid change in Hmg2p structure to a less
      accessible form. As in the living cell, the in vitro action of chemical
      chaperones was highly specific for Hmg2p and completely reversible. To evaluate
      the physiological relevance of this model behavior, we used the limited
      proteolysis assay to examine the effects of changing in vivo degradation signals
      on Hmg2p structure. We found that changes similar to those observed with chemical
      chaperones were brought about by alteration of natural degradation signal. Thus,
      Hmg2p can undergo significant, reversible structural changes that are relevant to
      the physiological control of Hmg2p ERAD. These findings support the idea that
      Hmg2p regulation is brought about by regulated alteration of folding state.
      Considering the ubiquitous nature of quality control pathways in biology, it may
      be that this strategy of regulation is widespread.

PMID- 14570926
TI  - The donor subsite of trehalose-6-phosphate synthase: binary complexes with UDP
      glucose and UDP-2-deoxy-2-fluoro-glucose at 2 A resolution.
AB  - Trehalose is an unusual non-reducing disaccharide that plays a variety of
      biological roles, from food storage to cellular protection from environmental
      stresses such as desiccation, pressure, heat-shock, extreme cold, and oxygen
      radicals. It is also an integral component of the cell-wall glycolipids of
      mycobacteria. The primary enzymatic route to trehalose first involves the
      transfer of glucose from a UDP-glucose donor to glucose-6-phosphate to form
      alpha,alpha-1,1 trehalose-6-phosphate. This reaction, in which the configurations
      of two glycosidic bonds are set simultaneously, is catalyzed by the
      glycosyltransferase trehalose-6-phosphate synthase (OtsA), which acts with
      retention of the anomeric configuration of the UDP-sugar donor. The
      classification of activated sugar-dependent glycosyltransferases into
      approximately 70 distinct families based upon amino acid sequence similarities
      places OtsA in glycosyltransferase family 20 (see afmb.cnrs-mrs.fr/CAZY/). The
      recent 2.4 A structure of Escherichia coli OtsA revealed a two-domain enzyme with
      catalysis occurring at the interface of the twin beta/alpha/beta domains. Here we
      present the 2.0 A structures of the E. coli OtsA in complex with either UDP-Glc
      or the non-transferable analogue UDP-2-deoxy-2-fluoroglucose. Both complexes
      unveil the donor subsite interactions, confirming a strong similarity to glycogen
      phosphorylases, and reveal substantial conformational differences to the
      previously reported complex with UDP and glucose 6-phosphate. Both the relative
      orientation of the two domains and substantial (up to 10 A) movements of an N
      terminal loop (residues 9-22) characterize the more open "relaxed" conformation
      of the binary UDP-sugar complexes reported here.

PMID- 14570927
TI  - Oligomerization and regulated proteolytic processing of angiopoietin-like protein
      4.
AB  - Angiopoietin-like protein 4 (Angptl4) is a recently identified circulating
      protein expressed primarily in adipose tissue and liver. Also known as peroxisome
      proliferator-activated receptor (PPAR)-gamma angiopoietin-related, fasting
      induced adipose factor, and hepatic fibrinogen/angiopoietin-related protein,
      recombinant Angptl4 causes increase of plasma very low density lipoprotein levels
      by inhibition of lipoprotein lipase activity. Similar to angiopoietins and other
      angiopoietin-like proteins, Angptl4 contains an amino-terminal coiled-coil domain
      and a carboxyl-terminal fibrinogen-like domain. We report here that Angptl4 is
      evolutionarily conserved among several mammalian species and that full-length
      Angptl4 protein is an oligomer containing intermolecular disulfide bonds.
      Oligomerized Angptl4 undergoes proteolytic processing to release its carboxyl
      fibrinogen-like domain, which circulates as a monomer. Angptl4's N-terminal
      coiled-coil domain mediates its oligomerization, which by itself is sufficient to
      form higher order oligomeric structure. Adenovirus-mediated overexpression of
      Angptl4 in 293 cells shows that conversion of full-length, oligomerized Angptl4
      is mediated by a cell-associated protease activity induced by serum. These
      findings demonstrate a novel property of angiopoietin-like proteins and suggest
      that oligomerization and proteolytic processing of Angptl4 may regulate its
      biological activities in vivo.

PMID- 14570928
TI  - Shear stress regulates endothelial nitric-oxide synthase promoter activity
      through nuclear factor kappaB binding.
AB  - We have previously demonstrated that shear stress increases transcription of the
      endothelial nitric-oxide synthase (eNOS) by a pathway involving activation of the
      tyrosine kinase c-Src and extracellular signal-related kinase 1/2 (ERK1/2). In
      the present study sought to determine the events downstream of this pathway.
      Shear stress activated a human eNOS promoter chloramphenicol acetyl-CoA
      transferase chimeric construct in a time-dependent fashion, and this could be
      prevented by inhibition of the c-Src and MEK1/2. Studies using electromobility
      shift assays, promoter deletions, and promoter mutations revealed that shear
      activation of the eNOS promoter was due to binding of nuclear factor kappaB
      subunits p50 and p65 to a GAGACC sequence -990 to -984 base pairs upstream of the
      eNOS transcription start site. Shear induced nuclear translocation of p50 and
      p65, and activation of the eNOS promoter by shear could be prevented by co
      transfection with a dominant negative I kappa Balpha. Exposure of endothelial
      cells to shear resulted in Ikappa kinase phosphorylation, and this was blocked by
      the MEK1/2 inhibitor PD98059 and the cSrc inhibitor PP1, suggesting these
      signaling molecules are upstream of NFkappaB activation. These experiments
      indicate that shear stress increases eNOS transcription by NFkappaB activation
      and p50/p65 binding to a GAGACC sequence present of the human eNOS promoter.
      While NFkappaB activation is generally viewed as a proinflammatory stimulus, the
      current data indicate that its transient activation by shear may increase
      expression of eNOS, which via production of nitric oxide could convey anti
      inflammatory and anti-atherosclerotic properties.

PMID- 14570929
TI  - Hepatic overexpression of murine Abcb11 increases hepatobiliary lipid secretion
      and reduces hepatic steatosis.
AB  - Abcb11 encodes for the liver bile salt export pump, which is rate-limiting for
      hepatobiliary bile salt secretion. We employed transthyretin-Abcb11 and BAC
      Abcb11 transgenes to develop mice overexpressing the bile salt export pump in the
      liver. The mice manifest increases in bile flow and biliary secretion of bile
      salts, phosphatidylcholine, and cholesterol. Hepatic gene expression of
      cholesterol 7alpha-hydroxylase and ileal expression of the apical sodium bile
      salt transporter are markedly reduced, whereas gene expression of targets of the
      nuclear bile salt receptor FXR (ileal lipid-binding protein, short heterodimer
      partner (SHP) is increased. Because these changes in gene expression are
      associated with an increased overall hydrophobicity of the bile salt pool and a 4
      fold increase of the FXR ligand taurodeoxycholate, they reflect bile salt
      mediated regulation of FXR and SHP target genes. Despite the increased biliary
      secretion of bile salts, fecal bile salt excretion is unchanged, suggestive of an
      enhanced enterohepatic cycling of bile salts. Abcb11 transgenic mice fed a
      lithogenic (high cholesterol/fat/cholic acid) diet display markedly reduced
      hepatic steatosis compared with wild-type controls. We conclude that mice
      overexpressing Abcb11 display an increase in biliary bile salt secretion and
      taurodeoxycholate content, which is associated with FXR/SHP-mediated changes in
      hepatic and ileal gene expression. Because these mice are resistant to hepatic
      lipid accumulation, regulation of Abcb11 may be important for the pathogenesis
      and treatment of steatohepatitis.

PMID- 14570930
TI  - Polycomb group suppressor of zeste 12 links heterochromatin protein 1alpha and
      enhancer of zeste 2.
AB  - Drosophila suppressor of zeste 12 (Su(z)12) is a Polycomb group (PcG)
      transcriptional repressor and is present in E(z)-ESC, a multiprotein complex with
      methylation activity specific for lysine 9 and 27 of histone H3. Although PcG-
      and heterochromatin-mediated gene silencing have been considered distinct, mutant
      flies of Su(z)12 showed not only homeotic transformation but also position effect
      variegation. We now report that the mammalian SU(Z)12 directly interacts with
      heterochromatin protein 1alpha (HP1alpha) and PcG enhancer of zeste 2 (EZH2), the
      mammalian counterpart of E(z), in vitro and in vivo. Two distinct domains in
      SU(Z)12 are involved in these interactions, the region between the zinc finger
      motif and the VEFS (VRN2-EMF2-FIS2-Su(z)12) box for HP1alpha (amino acid residues
      479-536) and the VEFS box for EZH2 (amino acid residues 600-639), which are not
      mutually exclusive. Interestingly this region of the VEFS box has been shown to
      be critical for the phenotype of the Su(z)12 mutant fly. In addition SU(Z)12
      represses transcription activity in the presence of HP1alpha in a reporter assay.
      These results provide a molecular explanation for the functional link of these
      epigenetic silencing processes mediated by Su(z)12.

PMID- 14570931
TI  - Fake worlds offer real medicine: virtual reality finding a role in treatment and
      training.

PMID- 14570932
TI  - Studies explore impact of new pathogens: investigators report on metapneumovirus,
      SARS.

PMID- 14570933
TI  - NIH: plan to speed biomedical payoffs.

PMID- 14570940
TI  - Optimal intervals and techniques for screening sigmoidoscopy.

PMID- 14570941
TI  - Optimal intervals and techniques for screening sigmoidoscopy.

PMID- 14570943
TI  - Optimal intervals and techniques for screening sigmoidoscopy.

PMID- 14570942
TI  - Safety of the smallpox vaccine among military recipients.

PMID- 14570944
TI  - Risk of neonatal death on weekends vs weekdays.

PMID- 14570945
TI  - Risk of neonatal death on weekends vs weekdays.

PMID- 14570946
TI  - Local vs central institutional review boards for multicenter studies.

PMID- 14570947
TI  - Lipid profiles in women with 45,X vs 46,XX primary ovarian failure.

PMID- 14570948
TI  - Comparison of screening mammography in the United States and the United kingdom.
AB  - CONTEXT: Screening mammography differs between the United States and the United
      Kingdom; a direct comparison may suggest methods to improve the practice.
      OBJECTIVE: To compare screening mammography performance between the United States
      and the United Kingdom among similar-aged women. DESIGN, SETTING, AND
      PARTICIPANTS: Women aged 50 years or older were identified who underwent 5.5
      million mammograms from January 1, 1996, to December 31, 1999, within 3 large
      scale mammography registries or screening programs: the Breast Cancer
      Surveillance Consortium (BCSC, n = 978 591) and National Breast and Cervical
      Cancer Early Detection Program (NBCCEDP, n = 613 388) in the United States; and
      the National Health Service Breast Screening Program (NHSBSP, n = 3.94 million)
      in the United Kingdom. A total of 27 612 women were diagnosed with breast cancer
      (invasive or ductal carcinoma in situ) within 12 months of screening among the 3
      groups. MAIN OUTCOME MEASURES: Recall rates (recommendation for further
      evaluation including diagnostic imaging, ultrasound, clinical examination, or
      biopsy) and cancer detection rates were calculated for first and subsequent
      mammograms, and within 5-year age groups. RESULTS: Recall rates were
      approximately twice as high in the United States than in the United Kingdom for
      all age groups; however, cancer rates were similar. Among women aged 50 to 54
      years who underwent a first screening mammogram, 14.4% in the BCSC and 12.5% in
      the NBCCEDP were recalled for further evaluation vs only 7.6% in the NHSBSP.
      Cancer detection rates per 1000 mammogram screens were 5.8, 5.9, and 6.3, in the
      BCSC, NBCCEDP, and NHSBSP, respectively. Recall rates were lower for subsequent
      examinations in all 3 settings but remained twice as high in the United States. A
      similar percentage of women underwent biopsy in each setting, but rates of
      percutaneous biopsy were lower and open surgical biopsy higher in the United
      States. Open surgical biopsies not resulting in a diagnosis of cancer (negative
      biopsies) were twice as high in the United States than in the United Kingdom.
      Based on a 10-year period of screening 1000 women aged 50 to 59 years, 477, 433,
      and 175 women in the BCSC, NBCCEDP, and NHSBSP, respectively, would be recalled;
      and for women aged 60 to 69 years, 396, 334, and 133 women, respectively. The
      estimated cancer detection rates per 1000 women aged 50 to 59 years were 24.5,
      23.8, and 19.4, respectively, and for women aged 60 to 69 years, 31.5, 26.6, and
      27.9, respectively. CONCLUSIONS: Recall and negative open surgical biopsy rates
      are twice as high in US settings than in the United Kingdom but cancer detection
      rates are similar. Efforts to improve US mammographic screening should target
      lowering the recall rate without reducing the cancer detection rate.

PMID- 14570949
TI  - Psychosocial factors and risk of hypertension: the Coronary Artery Risk
      Development in Young Adults (CARDIA) study.
AB  - CONTEXT: Although psychosocial factors are correlated, previous studies on risk
      factors for hypertension have typically examined psychosocial factors
      individually and have yielded inconsistent findings. OBJECTIVE: To examine the
      role of psychosocial factors of time urgency/impatience (TUI), achievement
      striving/competitiveness (ASC), hostility, depression, and anxiety on long-term
      risk of hypertension. DESIGN, SETTING, AND STUDY POPULATION: A population-based,
      prospective, observational study using participant data from the Coronary Artery
      Risk Development in Young Adults (CARDIA) study. A total of 3308 black and white
      adults aged 18 to 30 years (when recruited in 1985 and 1986) from 4 US
      metropolitan areas and followed up through 2000 to 2001. MAIN OUTCOME MEASURES:
      Fifteen-year cumulative incidence of hypertension (systolic blood pressure of 140
      mm Hg or higher, diastolic blood pressure of 90 mm Hg or higher, or taking
      antihypertensive medication). RESULTS: The incidence of hypertension at year 15
      was 15% from baseline and 13.6% from year 5. After adjusting for the same set of
      hypertension risk factors and each of the psychosocial factors of TUI, ASC,
      hostility, depression, and anxiety in 5 separate logistic regression models,
      higher TUI and hostility were significantly associated with risk of developing
      hypertension at 15-year follow-up for the total sample. Compared with the lowest
      score group, the adjusted odds ratio (OR) for TUI was 1.51 (95% confidence
      interval [CI], 1.12-2.03) for a score of 1; 1.47 (95% CI, 1.08-2.02) for a score
      of 2; and 1.84 (95% CI, 1.29-2.62) for a score of 3 to 4 (P for trend =.001).
      Compared with the lowest quartile group, the adjusted OR for hostility was 1.06
      (95% CI, 0.76-1.47) for quartile 2; 1.38 (95% CI, 1.00-1.91) for quartile 3; and
      1.84 (95% CI, 1.33-2.54) for quartile 4 (P for trend <.001). No consistent
      patterns were found for ASC, depression, or anxiety. Race- and sex-specific
      analyses and multivariable models with simultaneous adjustment for all 5
      psychosocial factors and other hypertension risk factors had generally similar
      results. CONCLUSION: Among young adults, TUI and hostility were associated with a
      dose-response increase in the long-term risk of hypertension.

PMID- 14570950
TI  - Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor
      tyrosine kinase, in symptomatic patients with non-small cell lung cancer: a
      randomized trial.
AB  - CONTEXT: More persons in the United States die from non-small cell lung cancer
      (NSCLC) than from breast, colorectal, and prostate cancer combined. In
      preclinical testing, oral gefitinib inhibited the growth of NSCLC tumors that
      express the epidermal growth factor receptor (EGFR), a mediator of cell
      signaling, and phase 1 trials have demonstrated that a fraction of patients with
      NSCLC progressing after chemotherapy experience both a decrease in lung cancer
      symptoms and radiographic tumor shrinkages with gefitinib. OBJECTIVE: To assess
      differences in symptomatic and radiographic response among patients with NSCLC
      receiving 250-mg and 500-mg daily doses of gefitinib. DESIGN, SETTING, AND
      PATIENTS: Double-blind, randomized phase 2 trial conducted from November 2000 to
      April 2001 in 30 US academic and community oncology centers. Patients (N = 221)
      had either stage IIIB or IV NSCLC for which they had received at least 2
      chemotherapy regimens. INTERVENTION: Daily oral gefitinib, either 500 mg
      (administered as two 250-mg gefitinib tablets) or 250 mg (administered as one 250
      mg gefitinib tablet and 1 matching placebo). MAIN OUTCOME MEASURES: Improvement
      of NSCLC symptoms (2-point or greater increase in score on the summed lung cancer
      subscale of the Functional Assessment of Cancer Therapy-Lung [FACT-L] instrument)
      and tumor regression (>50% decrease in lesion size on imaging studies). RESULTS:
      Of 221 patients enrolled, 216 received gefitinib as randomized. Symptoms of NSCLC
      improved in 43% (95% confidence interval [CI], 33%-53%) of patients receiving 250
      mg of gefitinib and in 35% (95% CI, 26%-45%) of patients receiving 500 mg. These
      benefits were observed within 3 weeks in 75% of patients. Partial radiographic
      responses occurred in 12% (95% CI, 6%-20%) of individuals receiving 250 mg of
      gefitinib and in 9% (95% CI, 4%-16%) of those receiving 500 mg. Symptoms improved
      in 96% of patients with partial radiographic responses. The overall survival at 1
      year was 25%. There were no significant differences between the 250-mg and 500-mg
      doses in rates of symptom improvement (P =.26), radiographic tumor regression (P
      =.51), and projected 1-year survival (P =.54). The 500-mg dose was associated
      more frequently with transient acne-like rash (P =.04) and diarrhea (P =.006).
      CONCLUSIONS: Gefitinib, a well-tolerated oral EGFR-tyrosine kinase inhibitor,
      improved disease-related symptoms and induced radiographic tumor regressions in
      patients with NSCLC persisting after chemotherapy.

PMID- 14570951
TI  - Sustained effect of intensive treatment of type 1 diabetes mellitus on
      development and progression of diabetic nephropathy: the Epidemiology of Diabetes
      Interventions and Complications (EDIC) study.
AB  - CONTEXT: The Diabetes Control and Complications Trial (DCCT) demonstrated the
      benefits of intensive treatment of diabetes in reducing glycemic levels and
      slowing the progression of diabetic nephropathy. The DCCT cohort has been
      examined annually for another 8 years as part of the follow-up Epidemiology of
      Diabetes Interventions and Complications (EDIC) study. During the EDIC study,
      glycemic levels no longer differed substantially between the 2 original treatment
      groups. OBJECTIVE: To determine the long-term effects of intensive vs
      conventional diabetes treatment during the DCCT on kidney function during the
      EDIC study. DESIGN, SETTING, AND PARTICIPANTS: Observational study begun in 1993
      (following DCCT closeout) in 28 medical centers in the United States and Canada.
      Participants were 1349 (of 1375) EDIC volunteers who had kidney evaluation at
      years 7 or 8. MAIN OUTCOME MEASURES: Development of microalbuminuria, clinical
      grade albuminuria, hypertension, or increase in serum creatinine level. RESULTS:
      Results were analyzed by intention-to-treat analyses, comparing the 2 original
      DCCT treatment groups. New cases of microalbuminuria occurred during the EDIC
      study in 39 (6.8%) of the participants originally assigned to the intensive
      treatment group vs 87 (15.8%) of those assigned to the conventional-treatment
      group, for a 59% (95% confidence interval [CI], 39%-73%) reduction in odds,
      adjusted for baseline values, compared with a 59% (95% CI, 36%-74%) reduction at
      the end of the DCCT (P<.001 for both comparisons). New cases of clinical
      albuminuria occurred in 9 (1.4%) of the participants in the original intensive
      treatment group vs 59 (9.4%) of those in the original conventional-treatment
      group, representing an 84% reduction in odds (95% CI, 67%-92%), compared with a
      reduction of 57% (95% CI, -1% to +81%) at the end of the DCCT. Fewer cases of
      hypertension (prevalence at year 8, 29.9% vs 40.3%; P<.001) developed in the
      original intensive-treatment group. Significantly fewer participants reached a
      serum creatinine level of 2 mg/dL or greater in the intensive-treatment vs the
      conventional-treatment group (5 vs 19, P =.004), but there were no differences in
      mean log clearance values. Although small numbers of patients required dialysis
      and/or transplantation, fewer patients experienced either of these outcomes in
      the intensive group (4 vs 7, P =.36). CONCLUSIONS: The persistent beneficial
      effects on albumin excretion and the reduced incidence of hypertension 7 to 8
      years after the end of the DCCT suggest that previous intensive treatment of
      diabetes with near-normal glycemia during the DCCT has an extended benefit in
      delaying progression of diabetic nephropathy.

PMID- 14570952
TI  - Bile duct injury during cholecystectomy and survival in medicare beneficiaries.
AB  - CONTEXT: Common bile duct (CBD) injury during cholecystectomy is a significant
      source of patient morbidity, but its impact on survival is unclear. OBJECTIVE: To
      demonstrate the relation between CBD injury and survival and to identify the
      factors associated with improved survival among Medicare beneficiaries. DESIGN,
      SETTING, AND PATIENTS: Retrospective study using Medicare National Claims History
      Part B data (January 1, 1992, through December 31, 1999) linked to death records
      and to the American Medical Association's (AMA's) Physician Masterfile. Records
      with a procedure code for cholecystectomy were reviewed and those with an
      additional procedure code for repair of the CBD within 365 days were defined as
      having a CBD injury. MAIN OUTCOME MEASURE: Survival after cholecystectomy,
      controlling for patient (sex, age, comorbidity index, disease severity) and
      surgeon (procedure year, case order, surgeon specialty) characteristics. RESULTS:
      Of the 1 570 361 patients identified as having had a cholecystectomy (62.9%
      women), 7911 patients (0.5%) had CBD injuries. The entire population had a mean
      (SD) age of 71.4 (10.2) years. Thirty-three percent of all patients died within
      the 9.2-year follow-up period (median survival, 5.6 years; interquartile range,
      3.2-7.4 years), with 55.2% of patients without and 19.5% with a CBD injury
      remained alive. The adjusted hazard ratio (HR) for death during the follow-up
      period was significantly higher (2.79; 95% confidence interval [CI]; 2.71-2.88)
      for patients with a CBD injury than those without CBD injury. The hazard
      significantly increased with advancing age and comorbidities and decreased with
      the experience of the repairing surgeon. The adjusted hazard of death during the
      follow-up period was 11% greater (HR, 1.11; 95% CI, 1.02-1.20) if the repairing
      surgeon was the same as the injuring surgeon. CONCLUSIONS: The association
      between CBD injury during cholecystectomy and survival among Medicare
      beneficiaries is stronger than suggested by previous reports. Referring patients
      with CBD injuries to surgeons or institutions with greater experience in CBD
      repair may represent a system-level opportunity to improve outcome.

PMID- 14570953
TI  - Prognostic importance of physical examination for heart failure in non-ST
      elevation acute coronary syndromes: the enduring value of Killip classification.
AB  - CONTEXT: In acute myocardial infarction, the presence and severity of heart
      failure at the time of initial presentation have been formally categorized by the
      Killip classification. Although well studied in ST-elevation myocardial
      infarction, the prognostic importance of Killip classification in non-ST
      elevation acute coronary syndromes is not well established. OBJECTIVES: To
      determine the prognostic importance of physical examination for heart failure
      analyzed according to Killip classification in non-ST-elevation acute coronary
      syndromes and to understand its predictive value relative to other variables.
      DESIGN, SETTING, AND PATIENTS: From April 2001 to September 2003, We analyzed
      information from 26 090 patients with non-ST-elevation acute coronary syndromes
      enrolled in the GUSTO IIb, PURSUIT, PARAGON A, and PARAGON B trials. Demographic
      information was categorized by Killip class. Killip classes III and IV were
      combined into 1 category. Multivariate Cox proportional hazard models were
      developed to determine the prognostic importance of Killip classification in
      comparison with other variables. MAIN OUTCOME MEASURE: Association between Killip
      classification and all-cause mortality at 30 days and 6 months. RESULTS: Patients
      in Killip class II (n = 2513) and III/IV (n = 390) were older than those in
      Killip class I (n = 23 187), with higher rates of diabetes, prior myocardial
      infarction, ST depression, and elevated cardiac enzymes (all P<.001). Higher
      Killip class was associated with higher mortality at 30 days (2.8% in Killip
      class I vs 8.8% in class II vs 14.4% in class III/IV; P<.001) and 6 months (5.0%
      vs 14.7% vs 23.0%, respectively; P<.001). Patients with Killip class II, III, or
      IV constituted 11% of the overall population but accounted for approximately 30%
      of the deaths at both time points. In multivariate analysis, Killip class III/IV
      was the most powerful predictor of mortality at 30 days (hazard ratio [HR], 2.35;
      95% confidence interval [CI], 1.69-3.26; P<.001) and 6 months (HR, 2.12; 95% CI,
      1.63-2.75; P<.001). Killip class II was predictive of mortality at 30 days (HR,
      1.73; 95% CI, 1.44-2.09; P<.001) and 6 months (HR, 1.52; 95% CI, 1.31-1.76;
      P<.001). Five factors-age, Killip classification, heart rate, systolic blood
      pressure, and ST depression-provided more than 70% of the prognostic information
      for 30-day and 6-month mortality. CONCLUSIONS: Killip classification is a
      powerful independent predictor of all-cause mortality in patients with non-ST
      elevation acute coronary syndromes. Age, Killip classification, heart rate,
      systolic blood pressure, and ST depression should receive particular attention in
      the initial assessment of these patients.

PMID- 14570954
TI  - A 60-year-old woman with atrial fibrillation.

PMID- 14570956
TI  - JAMA patient page. Type 1 diabetes.

PMID- 14570955
TI  - Psychosocial risk factors for cardiovascular disease: more than one culprit at
      work.

PMID- 14570957
TI  - Directions in environmental gerontology: a multidisciplinary field.
AB  - This article considers developments and directions for environmental gerontology
      drawing on the three papers in this Forum. The multidisciplinary field came of
      age during the 1960s with Powell Lawton's powerful environmental press paradigm
      and its applications to empirical research and building design. Recent
      theoretical developments in Europe and America have advanced and integrated
      concepts in psychology, geography, and related disciplines. Time dimensions and
      active use of space are essential for understanding aging individuals and
      microenvironments as well as changing populations and macroenvironments. Research
      on residential environments by health professions is informing community care
      that is enhancing the independence and well-being of older people. With its
      proven responsiveness to social and policy priorities, environmental gerontology
      is now providing strong conceptual and empirical bases for advancing healthy
      aging and age-friendly societies.

PMID- 14570958
TI  - Environmental gerontology at the beginning of the new millennium: reflections on
      its historical, empirical, and theoretical development.
AB  - Over the past four decades the environmental context of aging has come to play an
      important role in gerontological theory, research, and practice. Environmental
      gerontology (EG)--focused on the description, explanation, and modification or
      optimization of the relation between elderly persons and their sociospatial
      surroundings--has emerged as a subfield in its own right. The aim of this article
      is to reflect on the historical, empirical, and theoretical development of recent
      EG, following Parmelee and Lawton's diagnosis from 1990 that there is a need to
      move the field beyond its current languishing state. From a historical
      perspective, EG has clearly played an important and successful role within the
      gerontology enterprise in terms of explicit consideration of the sociophysical
      environment in theory and research. A literature analysis of empirical studies
      supports the view that research has continued on a substantial quantitative level
      during the 1990s. Findings of these research studies address the whole diversity
      of classic EG research questions, but mostly in the sense of replication and
      extension. In terms of theoretical discussion, our analysis leads to the insight
      that EG may be described as a field high in conceptual aspiration ("world
      views"), but low with regard to making research and application-productive use of
      its theoretical achievements.

PMID- 14570959
TI  - Conducting research on home environments: lessons learned and new directions.
AB  - The study of home environments is a research domain within the field of
      environmental gerontology that addresses issues related to aging in place.
      Despite the importance of aging at home, there are few recent studies in this
      area and most are descriptive and lack theoretical direction. This article
      examines the current state of research on home environments from which
      methodological challenges and new directions for future research are identified.
      Three broad research queries are posed: What should we measure and why in home
      environments? How do older people and their family members use the home
      environment in health, illness, and caregiving? What are the interrelationships
      between the home environment, psychological well-being, and daily functioning
      throughout the aging process? Suggestions for future research on home
      environments are discussed and the implications for advancing environmental
      gerontology highlighted. Specifically, the home environment offers a testing
      ground for generic environmental constructs and their measurement as well as a
      unique setting from which new understandings and constructs of person-environment
      fit can emerge.

PMID- 14570960
TI  - Conceptualizing time and behavior in environmental gerontology: a pair of old
      issues deserving new thought.
AB  - Architects, environmental designers, occupational therapists, and human service
      professionals are variously engaged in efforts to create settings for older
      persons that better fit their changing lifestyles and abilities. This theoretical
      article argues that to explain and predict more effectively the appropriateness
      of the settings occupied and used by their older occupants requires models and
      empirical inquiries that better conceptualize two areas of inquiry: (a) the
      temporal properties of environments and individuals and (b) the conceptualization
      of environmental behaviors or activities describing how individuals use,
      manipulate, or perform tasks in their settings. The types of constructs and
      relationships necessary for this inquiry are reviewed and their practical
      applications considered.

PMID- 14570961
TI  - Patterns and impact of comorbidity and multimorbidity among community-resident
      American Indian elders.
AB  - PURPOSE: The purpose of this study is to suggest a new approach to identifying
      patterns of comorbidity and multimorbidity. DESIGN AND METHODS: A random sample
      of 1,039 rural community-resident American Indian elders aged 60 years and older
      was surveyed. Comorbidity was investigated with four standard approaches, and
      with cluster analysis. RESULTS: Most respondents (57%) reported 3 or more of 11
      chronic conditions. Cluster analysis revealed a four-cluster comorbidity
      structure: cardiopulmonary, sensory-motor, depression, and arthritis. When the
      impact of comorbidity on four health-related quality of life outcomes was tested,
      the use of the clusters offered more explanatory power than the other approaches.
      IMPLICATIONS: Our study improves understanding of comorbidity within an
      understudied and underserved population by characterizing comorbidity in
      conventional and novel ways. The cluster approach has four advantages over
      previous approaches. In particular, cluster analysis identifies specific health
      problems that have to be addressed to alter American Indian elders' health
      related quality of life.

PMID- 14570962
TI  - The impact of hearing loss on quality of life in older adults.
AB  - PURPOSE: The authors investigate the impact of hearing loss on quality of life in
      a large population of older adults. DESIGN AND METHODS: Data are from the 5-year
      follow-up Epidemiology of Hearing Loss Study, a population-based longitudinal
      study of age-related hearing impairment conducted in Beaver Dam, WI. Participants
      (N = 2,688) were 53-97 years old (mean = 69 years) and 42% were male.
      Difficulties with communication were assessed by using the Hearing Handicap for
      the Elderly-Screening version (HHIE-S), with additional questions regarding
      communication difficulties in specific situations. Health-related quality of life
      was assessed by using measures of activities of daily living (ADLs), instrumental
      ADLs (IADLs) and the Short Form 36 Health Survey (SF-36). Hearing loss measured
      by audiometry was categorized on the basis of the pure-tone average of hearing
      thresholds at 0.5, 1, 2, and 4 kHz. RESULTS: Of participants, 28% had a mild
      hearing loss and 24% had a moderate to severe hearing loss. Severity of hearing
      loss was significantly associated with having a hearing handicap and with self
      reported communication difficulties. Individuals with moderate to severe hearing
      loss were more likely than individuals without hearing loss to have impaired ADLs
      and IADLs. Severity of hearing loss was significantly associated with decreased
      function in both the Mental Component Summary score and the Physical Component
      Summary score of the SF-36 as well as with six of the eight individual domain
      scores. IMPLICATIONS: Severity of hearing loss is associated with reduced quality
      of life in older adults.

PMID- 14570963
TI  - Neuropsychiatric symptoms in Latino elders with dementia or cognitive impairment
      without dementia and factors that modify their association with caregiver
      depression.
AB  - PURPOSE: The purpose of this study was to determine neuropsychiatric symptom
      frequency and intensity in demented and cognitively impaired but not demented
      Latino elderly persons, evaluate whether overall neuropsychiatric symptom
      intensity is associated with higher levels of caregiver depression, and identify
      factors that modify the relationship between neuropsychiatric symptoms and
      caregiver depression. DESIGN AND METHODS: Ninety-five elderly Latinos with
      dementia or cognitive impairment but not dementia (CIND), all of whom were
      identified through an ongoing epidemiological cohort study, and their informal
      caregivers participated in the study. Caregivers were interviewed in their homes,
      in either Spanish or English. The Neuropsychiatric Inventory was used to assess
      neuropsychiatric disturbances. RESULTS: For most neuropsychiatric symptoms,
      prevalence and intensity were significantly higher in the demented group compared
      with the CIND group. The overall neuropsychiatric symptom intensity score was
      significantly associated with caregiver depression. The strength and direction of
      the association of neuropsychiatric symptoms with caregiver depression was found
      to vary by three factors: whether the caregiver was the care recipient's spouse,
      whether the care recipient had dementia or CIND, and the care recipient's age.
      IMPLICATIONS: Neuropsychiatric symptoms may play a significant role in caregiver
      depression among Latino families. However, the impact of neuropsychiatric
      disturbances on Latino caregivers may differ depending on characteristics of both
      the caregiver and care recipient. The adverse impact of neuropsychiatric symptoms
      on caregivers of elderly persons with CIND has not been previously reported and
      deserves further study.

PMID- 14570964
TI  - Anger and depression management: psychoeducational skill training interventions
      for women caregivers of a relative with dementia.
AB  - PURPOSE: This study examines the short-term impact of two theoretically based
      psychoeducational small group interventions with distressed caregivers, and it
      also examines the role of specific moderator and mediator variables on caregiver
      outcomes. DESIGN AND METHODS: Female participants (N = 169) aged 50 and older who
      were caring for a community-dwelling relative with a dementing illness were
      randomly assigned to one of three treatment interventions: anger management,
      depression management, or a wait-list control group. These interventions took
      place over a 3- to 4-month period. The primary outcomes examined were anger or
      hostile mood, depressed mood, frequency of use of positive and negative coping
      strategies, and perceived caregiving self-efficacy. RESULTS: Significant main
      effects in the expected direction were found for changes in most of these
      measures. Participants in both anger management and depression management groups
      had significant reductions in their levels of anger or hostility and depression
      from Time 1 to Time 2 in comparison to participants in the wait-list control
      group. Use of positive cognitive coping strategies increased in the anger
      management group only. Self-efficacy significantly increased for participants in
      both intervention groups, and it was also demonstrated to function as a mediator
      of intervention effects. Pretreatment levels of depressive symptoms and anger
      expression style (Anger Expression-Out) moderated the relative effects of the two
      interventions on mood and coping. IMPLICATIONS: These data are consistent with a
      growing body of evidence supporting the effectiveness of skills training, in
      small groups, to improve both the affective states and the type of coping
      strategies used by caregivers. In addition, this study underscores the need to
      evaluate key pretreatment variables in order to determine which form of treatment
      may be more compatible with caregiver characteristics and thus more likely to be
      beneficial to individuals.

PMID- 14570965
TI  - Effects of facility characteristics on departures from assisted living: results
      from a national study.
AB  - PURPOSE: Assisted living is an increasingly important residential setting for the
      frail elderly person. How often and why residents leave such facilities are
      important issues for consumers, for clinicians advising frail patients on their
      options for living arrangements, and for policymakers. This research investigated
      the impact of facility and individual characteristics on residents' departures
      from assisted living. DESIGN AND METHODS: This research is based on data on 1,483
      residents in a nationally representative sample of 278 assisted living facilities
      (ALFs). Analyses of these data from 1998 and 1999 especially focused on those
      residents who left a study ALF between baseline and follow-up data collection.
      Multinomial logit models were estimated to investigate the impact of facility and
      individual factors on residents' status at follow-up. RESULTS: Over three
      quarters of those leaving their baseline ALF did so because they needed more
      care. The multivariate analyses indicated that poorer functional status and being
      married affected residents' relative odds of death before follow-up. Moving to
      another setting, other than a nursing home, was more likely for residents in for
      profit ALFs. Functional status, cognitive status, and the presence of a full-time
      RN affected residents' odds of moving from an ALF to a nursing home.
      IMPLICATIONS: Both facility-level and individual-level factors affected
      residents' relative odds of leaving an ALF. The findings with the most
      potentially interesting policy implications are those concerning the factors that
      affected residents' relative likelihoods of entering a nursing home.

PMID- 14570966
TI  - Environmental correlates to behavioral health outcomes in Alzheimer's special
      care units.
AB  - PURPOSE: We systematically measured the associations between environmental design
      features of nursing home special care units and the incidence of aggression,
      agitation, social withdrawal, depression, and psychotic problems among persons
      living there who have Alzheimer's disease or a related disorder. DESIGN AND
      METHODS: We developed and tested a model of critical health-related environmental
      design features in settings for people with Alzheimer's disease. We used
      hierarchical linear modeling statistical techniques to assess associations
      between seven environmental design features and behavioral health measures for
      427 residents in 15 special care units. Behavioral health measures included the
      Cohen-Mansfield physical agitation, verbal agitation, and aggressive behavior
      scales, the Multidimensional Observation Scale for Elderly Subjects depression
      and social withdrawal scales, and BEHAVE-AD (psychotic symptom list)
      misidentification and paranoid delusions scales. Statistical controls were
      included for the influence of, among others, cognitive status, need for
      assistance with activities of daily living, prescription drug use, amount of
      Alzheimer's staff training, and staff-to-resident ratio. Although hierarchical
      linear modeling minimizes the risk of Type II-false positive-error, this
      exploratory study also pays special attention to avoiding Type I error-the
      failure to recognize possible relationships between behavioral health
      characteristics and independent variables. RESULTS: We found associations between
      each behavioral health measure and particular environmental design features, as
      well as between behavioral health measures and both resident and nonenvironmental
      facility variables. IMPLICATIONS: This research demonstrates the potential that
      environment has for contributing to the improvement of Alzheimer's symptoms. A
      balanced combination of pharmacologic, behavioral, and environmental approaches
      is likely to be most effective in improving the health, behavior, and quality of
      life of people with Alzheimer's disease.

PMID- 14570967
TI  - Exploring assistance in Sweden and the United States.
AB  - PURPOSE: Few international comparisons of health services are performed using
      microlevel data. Using such data, this paper compares the need for and receipt of
      assistance with activities of daily living (ADLs) in comparable samples in the
      United States and Sweden, a country with a universal system of community-based
      services. DESIGN AND METHODS: Data from national surveys of community residents
      completed at approximately the same time in each nation are used to create
      comparable measures of need and assistance. Descriptive and logistic regression
      analyses compare need and assistance patterns across the nations and identify
      individual factors that explain receipt of assistance and unmet needs. RESULTS:
      Our results indicate that a simple story of greater use of paid formal services
      in Sweden and more unpaid informal use in the United States masks a more complex
      relationship. Assistance with ADLs seems to be more targeted in Sweden; narrow
      differences in assistance widen considerably when the analysis is limited to
      those reporting need. IMPLICATIONS: Although these two different health systems
      result in similar levels of overall ADL assistance, a detailed microlevel
      comparison reveals key distinctions. Further microlevel comparisons of access,
      cost, and quality in cross-national data can further aid our understanding of the
      consequences of health policy.

PMID- 14570968
TI  - Stagnation in mortality decline among elders in the Netherlands.
AB  - PURPOSE: This study assesses whether the stagnation of old-age (80+) mortality
      decline observed in The Netherlands in the 1980s continued in the 1990s and
      determines which factors contributed to this stagnation. Emphasis is on the role
      of smoking. DESIGN AND METHODS: Poisson regression analysis with linear splines
      was applied to total and cause-specific mortality data by age, year of death
      (1950-1999), and sex. An age-period-cohort analysis was carried out to determine
      whether the trends followed period or cohort patterns. ICD revisions were bridged
      by use of a concordance table. RESULTS: A sudden reversal in old-age mortality
      decline occurred around 1980, leading to a stagnation of the decline and even
      increases in mortality thereafter. Smoking-related cancers, chronic obstructive
      pulmonary disease, and diseases specifically related to old age contributed to
      this stagnation. Trends in smoking-related cancers and chronic obstructive
      pulmonary disease showed a cohort pattern--especially for men. When these smoking
      related diseases were excluded, the trends in old-age mortality in The
      Netherlands showed an increasing stagnation for both sexes. IMPLICATIONS: Smoking
      behavior can only partly explain the stagnation of mortality. Other factors such
      as increased frailty and changes in medical and social services for elderly
      people probably played a more decisive role in the recent stagnation.

PMID- 14570969
TI  - Definition of successful aging by elderly Canadian males: the Manitoba Follow-up
      Study.
AB  - PURPOSE: Although the concept of successful aging is used widely in the field of
      gerontology, there is no agreed-on standard or common underlying definition for
      measuring success in aging. Our recent survey of an elderly male population asked
      respondents to define "successful aging." This paper describes the themes that
      evolved from those definitions, explores interrelationships between the themes,
      and examines the association between characteristics of respondents and the
      themes provided in their definition. DESIGN AND METHODS: The Manitoba Follow-up
      Study has followed a cohort of 3,983 World War II Royal Canadian Air Force male
      aircrew recruits since July 1, 1948. At a mean age of 78 years in 1996, the
      survivors were surveyed and asked, "What is your definition of successful aging?"
      and "Would you say you have aged successfully?" A content analysis identified
      themes emerging from their definitions. RESULTS: The most frequent of the 20
      component themes from the definitions of successful aging as provided by 30% of
      the 1,771 respondents related to "health and disease"; "physical," "mental," and
      "social activity" were more likely to be found in a definition including
      "interest," "having goals," "family," or "diet," and they were less likely to be
      mentioned with themes of "independence" or "health." Many of the themes reflect
      an individual's attitudes toward life and the aging process. Current life
      satisfaction, self-rated health, and limitation in activities of daily living
      were significantly associated with an increased likelihood of reporting specific
      themes in definitions. IMPLICATIONS: As health care professionals adapt to the
      changing demographic composition of society, it should be of interest to
      understand what successful aging might mean to the elderly males to whom they are
      attending.

PMID- 14570970
TI  - Themes from a grounded theory analysis of elder neglect assessment by experts.
AB  - PURPOSE: This paper describes one program that has developed a screening
      procedure for assessing elder mistreatment, with a special focus on elder
      neglect. The aim is to understand how expert neglect assessment teams process and
      diagnose complex geriatric cases referred for suspected elder neglect. What are
      the key themes that must be understood in order to determine if neglect should be
      suspected and confirmed? DESIGN AND METHODS: Transcripts of audio recordings of
      neglect assessment team meetings were analyzed by using grounded theory analysis.
      RESULTS: Four major themes emerged from the analysis of the transcripts. These
      themes were understanding the underlying health status of the elder and
      caregiver, understanding the socioeconomic and life circumstances of the dyad,
      credibility of data collected by others, and the consequences of the assessment
      outcome. IMPLICATIONS: These findings offer insight into the development of
      future clinical screening and assessment procedures used to make diagnoses about
      elder neglect, as well as the guidelines that govern neglect assessment.
      Understanding not only the high-risk signs and symptoms but also the context and
      consequences of neglect is critical. Future screening and assessment procedures
      should be developed with these data in mind.

PMID- 14570971
TI  - Vulnerability to elder abuse and neglect in assisted living facilities.
AB  - PURPOSE: The purpose of this study was to examine the decision-making abilities
      of residents in assisted living regarding abuse and neglect. DESIGN AND METHODS:
      Twenty-seven residents in assisted living facilities were recruited for this
      descriptive study. Participants were administered an interview to assess baseline
      knowledge of support services, including ombudsman programs. They were next asked
      to watch videotaped scenarios of common types of elder abuse (physical, verbal,
      fiduciary, neglect) and asked to identify abusive situations. Finally, the
      participants were asked to develop a plan of action if they were to experience
      similar situations. RESULTS: The results suggested poor awareness of available
      elder support services (M = 25%). Residents performed fairly well in the simple
      identification of the abusive situations (54%), but had difficulty generating
      acceptable strategies for handling abusive situations. Approximately 25% had no
      suggestion, 50% reported they would consult a family member, and 25% had
      nonspecific suggestions (e.g., talk to staff about problem). IMPLICATIONS: The
      results of this study suggest that residents of assisted living facilities are
      poorly informed about protective services and uncertain about options if care
      were not optimal. Further work with larger samples is needed to confirm these
      results.

PMID- 14570972
TI  - Disciplinary perspectives on later-life migration in the core journals of social
      gerontology.
AB  - PURPOSE: The authors examine the bibliographic structure of recent research on
      later-life migration, highlighting the contributions of particular journals and
      disciplines. DESIGN AND METHODS: The authors identify the primary journals
      publishing research in this area, including a set of four core journals within
      the field of social gerontology. They evaluate the disciplinary affiliations of
      authors publishing in the core journals and the extent to which those journals
      cite relevant research published elsewhere. RESULTS: Geographical and economic
      perspectives on later-life migration are underrepresented within the core
      journals of social gerontology. In particular, major articles published outside
      the core journals are seldom cited within those journals. IMPLICATIONS: Although
      the core journals of social gerontology account for over a third of the recent
      literature on later-life migration, they present only a partial (chiefly
      sociological) perspective on the subject.

PMID- 14570973
TI  - Angels of the night: evening and night patrols for homebound elders in Sweden.
AB  - PURPOSE: The purpose of this study was to describe the work of evening and night
      home care patrols in Swedish old-age care by examining how staff members view
      their work and the specific work content. DESIGN AND METHODS: The authors
      developed two questionnaires: one that was to be answered jointly by the patrol
      teams, and one to be completed by each individual member of a team. All patrols
      in the municipality of Jonkoping, Sweden, were asked to participate. RESULTS: The
      most frequent kind of help provided by evening and night patrols involves
      personal care, but help with medications and injections are also frequent. The
      staff reported that it is becoming more common for the patrols to assist people
      with terminal illnesses. The patrols also increasingly assist people with
      psychiatric problems. The staff feels that the job may be becoming too diverse
      and that they need further education for the range of tasks they are asked to
      perform. IMPLICATIONS: The patrols are very flexible in the services provided.
      Without the patrols, the staff members believe that many persons would have to
      leave their homes to go to institutions.

PMID- 14570974
TI  - Bringing assisted living services into congregate housing: residents'
      perspectives.
AB  - PURPOSE: Bringing state-subsidized assisted living services (ALS) into congregate
      housing (CH) is a strategy for reducing rates of nursing home placement. This
      article discusses CH residents' reactions as a new ALS program was introduced in
      their housing, and it provides recommendations for others who are considering the
      implementation of similar programs. DESIGN AND METHODS: Focus groups and face-to
      face interviews with residents in a CH facility explored their experiences over
      time with the new ALS program. Residents were interviewed before the program was
      initiated and 6 months later as a way to better understand their knowledge of and
      feelings about the program. RESULTS: A qualitative analysis of the interview data
      revealed several patterns of complex attitudes and emotions linked to the
      program. Although the overwhelming majority of residents endorsed the program as
      a way to avoid nursing home placement, few understood the features of the program
      (e.g., cost and eligibility requirements). ALS participants' accounts of services
      suggested the presence of a highly "medicalized" approach. IMPLICATIONS: When new
      community-based models are implemented for elders, policy makers need to evaluate
      how these programs affect quality of life. Further, program guidelines for
      bringing ALS into existing housing have to address how the program complements
      the home-like nature of the housing.

PMID- 14570978
TI  - Is reelin the answer to synapse elimination at the neuromuscular junction?
AB  - The formation of mature neuronal circuits during development involves elimination
      of a large number of synapses by activity-dependent processes. A recent study
      suggests that synapse elimination at the neuromuscular junction is impaired in
      reeler mutant mice, which are lacking the extracellular matrix protein Reelin. In
      this process, Reelin acts through an unexpected, proteolytic mechanism that is
      independent of Disabled 1, a cytoplasmic factor that mediates Reelin signaling in
      the central nervous system. This Perspective discusses possible models for Reelin
      function in the framework of activity-dependent synapse elimination at the
      neuromuscular junction.

PMID- 14570979
TI  - Monitoring signaling processes in living cells using biosensors.
AB  - This collection of nine animations shows how different types of biosensors report
      changes in cellular processes through the production of a visually detectable
      signal. Biosensors can be created by attaching one or more fluorescent proteins
      (such as green fluorescent protein) to a target protein or peptide or by
      attaching a fluorescent dye that is sensitive to its environment to a protein or
      peptide. Conformational changes in proteins in response to ligand binding,
      changes in the concentration of cellular metabolites or signaling messengers,
      changes in protein localization, and changes in protein activity or covalent
      modification can all be detected with biosensors. These animations can be used
      separately or together to illustrate how molecular biology, chemistry, and
      microscopy have converged to allow cellular processes to be visualized in living
      cells. Several of the animations describe the production of a fluorescent
      resonance energy transfer (FRET) signal.

PMID- 14570980
TI  - Autoimmune cardiomyopathy and heart block develop spontaneously in HLA-DQ8
      transgenic IAbeta knockout NOD mice.
AB  - A line of nonobese diabetic (NOD) mice expressing the human diabetes-associated
      HLA-DQ8 transgene in the absence of mouse IAbeta failed to show spontaneous
      insulitis or diabetes, but rather developed dilated cardiomyopathy, leading to
      early death from heart failure. Pathology in these animals results from an organ-
      and cell-specific autoimmune response against normal cardiomyoctes in the atrial
      and ventricular walls, as well as against very similar myocytes present in the
      outermost muscle layer surrounding the pulmonary veins. Progression of the
      autoimmune process could be followed by serial ECG measurements; irradiation of
      young animals significantly delayed disease progression, and this effect could be
      reversed by adoptive transfer of splenocytes taken from older animals with
      complete heart block. Disease progression could also be blocked by cyclosporin A
      treatment, but was accelerated by injection of complete Fruend's adjuvant. The
      constellation of findings of spontaneously arising destructive focal lymphocytic
      infiltrates within the myocardium, rising titers of circulating anticardiac
      autoantibodies, dilation of the cardiac chambers, and gradual progression to end
      stage heart failure bears a striking resemblance to what is seen in humans with
      idiopathic dilated cardiomyopathy, a serious and often life-threatening medical
      condition. This transgenic strain provides a highly relevant animal model for
      human autoimmune myocarditis and postinflammatory dilated cardiomyopathy.

PMID- 14570981
TI  - Serial analysis of gene expression in mouse kidney following angiotensin II
      administration.
AB  - As a new line of inquiry into the molecular mechanisms underlying
      pathophysiological processes associated with angiotensin (ANG II)-dependent
      hypertension, we applied the method of serial analysis of gene expression (SAGE)
      to examine genome-wide transcription changes in the kidneys of mice that
      developed hypertension in response to chronic ANG II administration. Mice were
      infused subcutaneously via osmotic minipumps with ANG II for 7 days, and systolic
      blood pressure was measured by tail-cuff plethysmography. Subsequently, mice were
      euthanized, and the total RNA isolated from the kidneys was used to construct
      SAGE libraries. Comparison of 11,447 SAGE tags from the hypertensive kidneys,
      representing 5,740 unique transcripts, and 11,273 tags from the control kidneys,
      corresponding to 5,619 different transcripts, identified genes that are
      significantly (P < 0.05) down- or upregulated in the hypertensive kidney. Our
      assessment of the genome-wide influence of ANG II resulted in the detection of
      several novel genes and in a recognition of potential new roles for the
      previously characterized genes, thus providing new probes with which to further
      explore the ANG II effects in normal and disease states.

PMID- 14570982
TI  - The intraclass correlation coefficient applied for evaluation of data correction,
      labeling methods, and rectal biopsy sampling in DNA microarray experiments.
AB  - We show that the intraclass correlation coefficient (ICC) can be used as a
      relatively simple statistical measure to assess methodological and biological
      variation in DNA microarray analysis. The ICC is a measure that determines the
      reproducibility of a variable, which can easily be calculated from an ANOVA
      table. It is based on the assessment of both systematic deviation and random
      variation, and it facilitates comparison of multiple samples at once. We used the
      ICC first to optimize our microarray data normalization method and found that the
      use of median values instead of mean values improves data correction. Then the
      reproducibility of different labeling methods was evaluated, and labeling by
      indirect fluorescent dye incorporation appeared to be more reproducible than
      direct labeling. Finally, we determined optimal biopsy sampling by analyzing
      overall variation in gene expression. The variation in gene expression of rectal
      biopsies within persons decreased when two biopsies were taken instead of one,
      but it did not considerably improve when more than two biopsies were taken from
      one person, indicating that it is sufficient to use two biopsies per person for
      DNA microarray analysis under our experimental conditions. To optimize the
      accuracy of the microarray data, biopsies from at least six different persons
      should be used per group.

PMID- 14570983
TI  - Microarray-based discovery of highly expressed olfactory mucosal genes: potential
      roles in the various functions of the olfactory system.
AB  - We sought to gain a global view of tissue-specific gene expression in the
      olfactory mucosa (OM), the major site of neurogenesis and neuroregeneration in
      adult vertebrates, by examination of its overexpressed genes relative to that in
      81 other developing and adult mouse tissues. We used a combination of statistical
      and fold-difference criteria to identify the top 269 cloned cDNAs from an array
      of 8,734 mouse cDNA elements on the Incyte Mouse GEM1 array. These clones,
      representing known and poorly characterized gene transcripts, were grouped
      according to their relative expression patterns across the other tissues and then
      further examined with respect to gene ontology categories. Approximately one
      third of the 269 genes were also highly expressed in developing and/or adult
      central nervous system tissues. Several of these have been suggested or
      demonstrated to play roles in neurogenesis, neuronal differentiation, and/or
      neuronal migration, further suggesting that many of the unknown genes that share
      this expression pattern may play similar roles. Highly OM-specific genes included
      a palate, lung, and nasal epithelium carcinoma-associated gene (Plunc);
      sphingosine phosphate lyase (Sgpl1), and paraoxonase 1 (Pon1). Cell-type-specific
      expression within OM was established using in situ hybridization for several
      representative expression pattern clusters. Using the ENSEMBL-assembled mouse
      genome and comparative genomics analyses to the human genome, we assigned many of
      the unknown expressed sequence tags (ESTs) and poorly characterized genes to
      either novel or known gene products and provided predictive classification.
      Further exploration of this database will provide additional insights into genes
      and pathways critical for olfactory neurogenesis, neuronal differentiation,
      olfaction, and mucosal defense.

PMID- 14570985
TI  - Editorial--a new method for generic measuring of the global quality of life.

PMID- 14570984
TI  - Transcriptome profiling of a Saccharomyces cerevisiae mutant with a
      constitutively activated Ras/cAMP pathway.
AB  - Often changes in gene expression levels have been considered significant only
      when above/below some arbitrarily chosen threshold. We investigated the effect of
      applying a purely statistical approach to microarray analysis and demonstrated
      that small changes in gene expression have biological significance. Whole genome
      microarray analysis of a pde2Delta mutant, constructed in the Saccharomyces
      cerevisiae reference strain FY23, revealed altered expression of approximately
      11% of protein encoding genes. The mutant, characterized by constitutive
      activation of the Ras/cAMP pathway, has increased sensitivity to stress, reduced
      ability to assimilate nonfermentable carbon sources, and some cell wall integrity
      defects. Applying the Munich Information Centre for Protein Sequences (MIPS)
      functional categories revealed increased expression of genes related to ribosome
      biogenesis and downregulation of genes in the cell rescue, defense, cell death
      and aging category, suggesting a decreased response to stress conditions. A
      reduced level of gene expression in the unfolded protein response pathway (UPR)
      was observed. Cell wall genes whose expression was affected by this mutation were
      also identified. Several of the cAMP-responsive orphan genes, upon further
      investigation, revealed cell wall functions; others had previously unidentified
      phenotypes assigned to them. This investigation provides a statistical global
      transcriptome analysis of the cellular response to constitutive activation of the
      Ras/cAMP pathway.

PMID- 14570986
TI  - Measurement of quality of life I. A methodological framework.
AB  - Despite the widespread acceptance of quality of life (QOL) as the ideal guideline
      in healthcare and clinical research, serious conceptual and methodological
      problems continue to plague this area. In an attempt to remedy this situation, we
      propose seven criteria that a quality-of-life concept must meet to provide a
      sound basis for investigation by questionnaire. The seven criteria or desiderata
      are: (1) an explicit definition of quality of life; (2) a coherent philosophy of
      human life from which the definition is derived; (3) a theory that
      operationalizes the philosophy by specifying unambiguous, nonoverlapping, and
      jointly exhaustive questionnaire items; (4) response alternatives that permit a
      fraction-scale interpretation; (5) technical checks of reproducibility; (6)
      meaningfulness to investigators, respondents, and users; and (7) an overall
      aesthetic appeal of the questionnaire. These criteria have guided the design of a
      validated 5-item generic, global quality-of-life questionnaire (QOL5), and a
      validated 317-item generic, global quality-of-life questionnaire (SEQOL),
      administered to a well-documented birth cohort of 7,400 Danes born in 1959-1961,
      as well as to a reference sample of 2,500 Danes. Presented in outline, the
      underlying integrative quality-of-life (IQOL) theory is a meta-theory. To
      illustrate the seven criteria at work, we show the extent to which they are
      satisfied by one of the eight component theories. Next, two sample results of our
      investigation are presented: satisfaction with one's sex life has the expected
      covariation with one's quality of life, and so does mother's smoking during
      pregnancy, albeit to a much smaller extent. It is concluded that the
      methodological framework presented has proved helpful in designing a
      questionnaire that is capable of yielding acceptably valid and reliable
      measurements of global and generic quality of life.

PMID- 14570987
TI  - Measurement of quality of life II. From the philosophy of life to science.
AB  - We believe it should be possible to make operational the philosophical ideas of
      the good life in order to make it the object of scientific research. The Quality
      of Life Research Center in Copenhagen, Denmark has therefore spent the last
      several years with these questions and tried to find practical and evidence-based
      scientific solutions. This paper describes the theoretical road taken in moving
      from the abstract philosophy of life to the actual questionnaire. It presents an
      important aspect of our work with the quality-of-life (QOL) concept though the
      last decade. We have developed the quality-of-life philosophy; the SEQOL, QOL5,
      and QOL1 questionnaires; the quality-of-life theory; and the quality-of-life
      research methodology. We carried out quality-of-life population surveys and
      developed techniques for improving quality of life with the chronically sick
      patient. This paper presents the struggle to create a rating scale for the
      generic measurement of the global quality of life, based on quality-of-life
      theory, derived from quality-of-life philosophy. The developed rating scale is a
      ratio scale combining a Likert scale, a visual analogue scale, and a numerical
      scale, to a reduced combination scale. This allows for the extraction of as much
      information from the respondents as possible without exhausting them unduly or
      demanding more than can be reasonably expected.

PMID- 14570988
TI  - Measurement of quality of life III. From the IQOL theory to the global, generic
      SEQOL questionnaire.
AB  - The Danish Quality of Life Survey is based on the philosophy of life known as the
      integrative quality-of-life (IQOL) theory. It consists of eight different quality
      of-life concepts, ranging from the superficially subjective via the deeply
      existential to the superficially objective (well being, satisfaction with life,
      happiness, meaning in life, biological order, realizing life potential,
      fulfillment of needs, and objective factors [ability of functioning and
      fulfilling societal norms]). This paper presents the work underlying the
      formulation of the theories of a good life and how these theories came to be
      expressed in a comprehensive, multidimensional, generic questionnaire for the
      evaluation of the global quality of life--SEQOL (self-evaluation of quality of
      life)--presented in full length in this paper. The instruments and theories on
      which the Quality of Life Survey was based are constantly being updated. It is an
      on-going process due to aspects such as human development, language, and culture.
      We arrived at eight rating scales for the quality of life that, guided by the
      IQOL theory, were combined into a global and generic quality-of-life rating
      scale. This was simplified to the validated QOL5 with only five questions, made
      for use in clinical databases. Unfortunately, the depth of human existence is to
      some extent lost in QOL5. We continue to aim towards greater simplicity,
      precision, and depth in the questions in order to explore the depths of human
      existence. We have not yet found a final form that enables us to fully rate the
      quality of life in practice. We hope that the several hundred questions we found
      necessary to adequately implement the theories of the Quality of Life Survey can
      be replaced by far fewer; ideally, only eight questions representing the eight
      component theories. These eight ideal questions have not yet been evaluated, and
      therefore they should not form the basis of a survey. However, the perspective is
      clear. If eight simple questions can accurately rate the quality of life as well
      as its depth, we have found an instrument of immense practical scope.

PMID- 14570989
TI  - Measurement of quality of life IV. Use of the SEQOL, QOL5, QOL1, and other global
      and generic questionnaires.
AB  - Quality-of-life (QOL) rating scales can be used to measure and describe the
      quality of life of a specific population or patient group. Many decisions can be
      taken and policies implemented when we know more about a group or population. The
      global quality-of-life concept may help in expressing the objective of the
      initiatives taken to benefit specific groups. The objective may be that we hope
      the efforts will increase their quality of life by a certain percentage. This
      explicit expectation will force the decision makers to stand by their noble
      intentions. They are obliged to evaluate their efforts and will have to learn
      something from it. A questionnaire thus constitutes a useful scientific
      instrument, as databases based on comprehensive and thorough questionnaire
      surveys that seek to encompass all aspects of life can provide valuable and
      precise information. The value of such a database depends on the correct use of
      the questionnaires and this paper examines some examples of how quality-of-life
      rating scales can be used. We identified at least ten ways to use the quality-of
      life questionnaire: describing the quality of life of a population or patient
      group; formulating an objective for support, treatment, or care; screening or
      identifying individuals who need treatment; evaluating treatment and care;
      facilitating communication between physician and patients; involving the patient
      in the decision-making process; allocating resources; investigating the causal
      relation between the quality of life and ill health in prospective studies;
      creating an awareness of the quality of life and health promotion; and helping
      the practitioner to accumulate knowledge. Enhancing the quality of life is
      therefore a determining factor in the process of increasing awareness and
      responsible conduct in relation to the environment, natural resources, the
      working environment, and the structure of society. Putting the quality of life on
      the agenda inherently has a constructive and positive effect on the life and
      functioning of the individual and society.

PMID- 14570990
TI  - Measurement of quality of life V. How to use the SEQOL, QOL5, QOL1, and other
      global and generic questionnaires for research.
AB  - A survey can be divided into four phases: (1) planning, (2) distributing and
      collecting the questionnaires, (3) analysis, and (4) dissemination of the
      results. This paper provides step-by-step guidance on how the global and generic
      SEQOL (self-evaluated quality of life) and QOL5 questionnaires can be used in a
      large- or small-scale survey of quality of life (QOL). It covers what is required
      to conduct a survey and generate results that should be of interest to local
      politicians, decision makers, and representatives from the surveyed groups and
      should be published after it has been processed and edited. If the results are to
      be published in the scientific literature, it is necessary to seek the assistance
      of an expert in statistics and/or research and the dissemination of research
      results.

PMID- 14570991
TI  - Measurement of quality of life VI. Quality-adjusted life years (QALY) is an
      unfortunate use of the quality-of-life concept.
AB  - The QALY (quality-adjusted life years) attempts to incorporate the dimension of
      quality of life into the evaluation by adjusting life years by a quality factor.
      In practice, this is based on discussing with people the progression of a number
      of hypothetical illnesses and their ensuing side effects. From this information,
      the person assesses how each state of health described compares with a
      theoretical maximum state of health. For example, 1 day with a certain condition
      might the equivalent of living only 0.5 days in good health. We believe that QALY
      value only represents a superficial impression of a person's quality of life. In
      short, the QALY does not express what it means for a person to live a life at
      reduced quality. We believe that if the patients were optimally informed and
      allowed to decide for themselves, they would more often reject high-tech
      expensive biomedical treatments that only serve to prolong life and do not
      increase its quality. The problem of priorities may then turn out to be far more
      simple and also more ethical: the focus will be on the quality of life, not on
      QALY, and the question of the meaning of life and death will achieve greater
      openness and respect.

PMID- 14570992
TI  - Measurement of quality of life VII. Statistical covariation and global quality of
      life data: the method of weight-modified linear regression.
AB  - Existing standard statistical procedures do not seem to fulfill the needs of the
      researcher in global quality-of-life (QOL) research, because the most interesting
      question seems to be the exact size of statistical covariations. A method is
      necessary if we are to isolate the most important factors connected to quality of
      life among the thousands of possible factors in life. We have developed a new
      procedure we call "weight-modified linear regression". Unfortunately as
      demonstrated in the discussion, the procedure is not totally without problems and
      weaknesses. In spite of the critique, we believe the procedure to be valid for
      the purpose of estimating the size of the covariation in population studies
      including psychometric measures of global quality of life. As we need to be
      certain that the procedure is valid, we hereby invite the scientific community to
      give us further critique of the method and suggestions for its improvement.

PMID- 14570993
TI  - Quality of life theory I. The IQOL theory: an integrative theory of the global
      quality of life concept.
AB  - Quality of life (QOL) means a good life and we believe that a good life is the
      same as living a life with a high quality. This paper presents the theoretical
      and philosophical framework of the Danish Quality of Life Survey, and of the
      SEQOL, QOL5, and QOL1 questionnaires. The notion of a good life can be observed
      from subjective to the objective, where this spectrum incorporates a number of
      existing quality of life theories. We call this spectrum the integrative quality
      of-life (IQOL) theory and discuss the following aspects in this paper: well
      being, satisfaction with life, happiness, meaning in life, the biological
      information system ("balance"), realizing life potential, fulfillment of needs,
      and objective factors. The philosophy of life outlined in this paper tries to
      measure the global quality of life with questions derived from the integrative
      theory of the quality of life. The IQOL theory is an overall theory or meta
      theory encompassing eight more factual theories in a subjective-existential
      objective spectrum. Other philosophies of life can stress other aspects of life,
      but by this notion of introducing such an existential depth into the health and
      social sciences, we believe to have taken a necessary step towards a new humility
      and respect for the richness and complexity of life.

PMID- 14570994
TI  - Quality of life theory II. Quality of life as the realization of life potential:
      a biological theory of human being.
AB  - This review presents one of the eight theories of the quality of life (QOL) used
      for making the SEQOL (self-evaluation of quality of life) questionnaire or the
      quality of life as realizing life potential. This theory is strongly inspired by
      Maslow and the review furthermore serves as an example on how to fulfill the
      demand for an overall theory of life (or philosophy of life), which we believe is
      necessary for global and generic quality-of-life research. Whereas traditional
      medical science has often been inspired by mechanical models in its attempts to
      understand human beings, this theory takes an explicitly biological starting
      point. The purpose is to take a close view of life as a unique entity, which
      mechanical models are unable to do. This means that things considered to be
      beyond the individual's purely biological nature, notably the quality of life,
      meaning in life, and aspirations in life, are included under this wider,
      biological treatise. Our interpretation of the nature of all living matter is
      intended as an alternative to medical mechanism, which dates back to the
      beginning of the 20th century. New ideas such as the notions of the human being
      as nestled in an evolutionary and ecological context, the spontaneous tendency of
      self-organizing systems for realization and concord, and the central role of
      consciousness in interpreting, planning, and expressing human reality are
      unavoidable today in attempts to scientifically understand all living matter,
      including human life.

PMID- 14570995
TI  - Quality of life theory III. Maslow revisited.
AB  - In 1962, Abraham Maslow published his book Towards a Psychology of Being, and
      established a theory of quality of life, which still is considered a consistent
      theory of quality of life. Maslow based his theory for development towards
      happiness and true being on the concept of human needs. He described his approach
      as an existentialistic psychology of self-actualization, based on personal
      growth. When we take more responsibility for our own life, we take more of the
      good qualities that we have into use, and we become more free, powerful, happy,
      and healthy. It seems that Maslow's concept of self-actualization can play an
      important role in modern medicine. As most chronic diseases often do not
      disappear in spite of the best biomedical treatments, it might be that the real
      change our patients have for betterment is understanding and living the noble
      path of personal development. The hidden potential for improving life really lies
      in helping the patient to acknowledge that his or her lust for life, his or her
      needs, and his or her wish to contribute, is really deep down in human existence
      one and the same. But you will only find this hidden meaning of life if you
      scrutinize your own life and existence closely enough, to come to know your
      innermost self.

PMID- 14570996
TI  - Nature's wisdom during aneurysmal subarachnoid hemorrhage.

PMID- 14570997
TI  - Deep brain stimulation for Parkinson's disease.
AB  - Dopaminergic replacement therapy with levodopa/carbidopa is still the cornerstone
      for the treatment of Parkinson's disease (PD). However, the medical management of
      PD is complicated by the appearance of disabling motor response fluctuations,
      levodopa-induced dyskinesias and psychosis. Since the early 1990s, surgical
      therapies have made a rapid reentry into the therapeutic armamentarium for PD and
      deep brain stimulation (DBS) of the globus pallidus interna or subthalamic nuclei
      is currently the most promising of such interventions. Recognition of the
      physiological changes in basal ganglia circuits in animal models of PD has
      provided the much-needed theoretic basis for targeting these areas. DBS of these
      areas has proven to be a safe procedure and effective against all the major motor
      symptoms of PD. Though not curative it can substantially reduce motor response
      fluctuations, levodopa-induced dyskinesias, and improve the quality of life of
      these patients. DBS is an expensive treatment and hardware-related complications
      are not rare. The results of the procedure are dependent on careful patient
      selection and the experience of the performing team. An update on the principles,
      methods and results of such procedures is essential to raise the awareness of
      this new therapeutic modality and to provide guidelines to the referring
      physicians.

PMID- 14570998
TI  - Friedreich's ataxia--yesterday, today and tomorrow.
AB  - The present review traces the origin of Friedreich's Ataxia (FA) from the time of
      Nikolaus Friedreich in the mid-nineteenth century. The early hesitation on the
      part of the neurological community in accepting FA as a distinct entity, rather
      than a variant form of tabes dorsalis and multiple sclerosis, has been
      highlighted. Research within the last 6-7 years, has firmly established FA as a
      trinucleotide repeat disorder, the location of the offending gene, and the
      disease-related gene product, frataxin. Frataxin is now thought to interfere with
      the mitochondrial oxidative process and enhance iron accumulation. However,
      whether this iron accumulation is a primary causative event for symptom
      production is not clear and iron chelators are unlikely to be helpful in therapy.
      Of great promise is the use of free radical scavengers and antioxidants. One such
      agent idebenone, a short chain analogue of co-enzyme Q10, may have a future.

PMID- 14570999
TI  - Parkinsonism plus syndrome--a review.
AB  - Parkinsonism plus syndrome is a group of heterogeneous degenerative neurological
      disorders, which differ from the classical idiopathic Parkinson's disease in
      certain associated clinical features, poor response to levodopa, distinctive
      pathological characteristics and poor prognosis. Associated clinical features
      include symmetrical onset, infrequent or atypical tremor, prominent rigidity in
      axial musculature, bradykinesia, early postural instability, supranuclear gaze
      palsy, early autonomic failure, pyramidal affection, cerebellar involvement,
      alien limb phenomenon, apraxia and significant early cognitive dysfunction in
      some cases. Progressive supranuclear palsy (PSP), multiple system atrophy (MSA)
      and dementia with Lewy body disease (DLB) are commoner disorders. Less frequent
      disorders are cortico-basal ganglionic degeneration (CBGD), frontotemporal
      dementia with chromosome 17 (FTDP-17), Pick's disease, parkinsonian-dementia
      complex of Guam, Pallidonigral degeneration, Wilson's disease and a rigid variant
      of Huntington's disease. During the last 3 decades, major progress has been made
      in understanding PSP, CBGD and FTDP-17, which are tau disorders. MSA and DLB
      together with idiopathic Parkinson's disease are called alpha-synucleinopathies.
      Recent studies show that the diagnosis of these Parkinsonism plus syndromes
      improves when strict diagnostic criteria are used. However, unusual presentations
      may pose a diagnostic challenge. The shortcomings of the current studies demand
      the need for further research to identify biologic markers that may allow earlier
      diagnosis, and understanding of the factors leading to alpha-synuclein or tau
      aggregation. Identification of therapeutic strategies that may prevent the
      aggregation of these proteins and rescue dysfunctional cells has been stressed.
      This review focuses on the advances in the clinical, neuroimaging, pathologic,
      genetic and management aspects of these disorders.

PMID- 14571000
TI  - Measuring the corpus callosum in schizophrenia: a technique with neuroanatomical
      and cytoarchtectural basis.
AB  - BACKGROUND: Corpus Callosum (CC) abnormalities have been described in
      schizophrenia. Review of CC measurement methods in schizophrenia reveals
      inconsistency and lack of neuroanatomical basis. AIMS: The aims of the study are
      to describe a new CC measurement method with valid a neuroanatomical and
      cytoarchitectural basis and to demonstrate inter-rater reliability for the same.
      SETTINGS AND DESIGN: The study was performed in the National Institute of Mental
      Health & Neurosciences, Bangalore, India. Ours is a cross-sectional study in
      which both the first author and senior neuroradiologist were blind to clinical
      details. MATERIAL AND METHODS: We report a reliable, semi-automated CC measuring
      technique with a neuroanatomical and cytoarchitectural basis tested in a group of
      16 never-treated schizophrenia patients using 1-mm thick, objectively defined
      midsagittal MRI section. Measurement on coded slices using scion image software
      ensured elimination of rater bias. STATISTICAL ANALYSIS USED: The statistical
      analysis used for assessing inter-rater reliability is intraclass correlation
      coefficient analysis. RESULTS: The intraclass correlation coefficients for the CC
      measurements were as follows: CC Area = 0.93; Anterior CC area = 0.84; Area of
      body of the CC = 0.83; Area of CC isthmus = 0.65; Area of CC splenium = 0.88;
      maximum antero-posterior distance of CC = 0.96. CONCLUSION: Measurements showed
      good inter-rater reliability. The methodology demonstrated in our study is
      simple, relevant, reliable and can be used for future schizophrenia research.

PMID- 14571001
TI  - Foramen magnum tumors: a series of 30 cases.
AB  - BACKGROUND AND AIMS: Foramen magnum tumors, especially those located ventrally,
      are surgically challenging. We studied clinical and surgical details of
      extramedullary tumors located in the region of the foramen magnum. MATERIAL AND
      METHODS: A series of 30 cases of extramedullary tumors at the foramen magnum,
      operated over a period of 8 years is presented. RESULTS: There were 10
      neurofibromas, 8 meningiomas, 6 chordomas, 2 tuberculomas and 4 miscellaneous
      tumors. The clinical profile consisted of sensory symptoms in all the patients,
      quadriparesis in 24, lower cranial nerve affection in 8 and sphincter
      disturbances in 6 patients. The surgical approaches consisted of an extreme
      lateral approach in 10, a posterior or posterolateral approach in 18 and a per
      oral route in 2 cases. Total excision of the tumor was performed in 24 and a
      subtotal excision of the tumor was done in 6 cases. Two patients died, one due to
      meningitis and the other due to chest infection. Eight other patients had
      complications like CSF leak, meningitis, pseudomeningocele, laryngeal edema, and
      transient worsening of neurological deficits. CONCLUSIONS: Foramen magnum tumors
      have long been regarded as difficult lesions both in terms of diagnosis and
      management. However, with the availability of MR imaging, newer surgical
      techniques and skull basal exposures, the excision of these lesions is becoming
      easier and safer.

PMID- 14571002
TI  - Intraventricular sodium nitroprusside therapy: a future promise for refractory
      subarachnoid hemorrhage-induced vasospasm.
AB  - A prospective study was carried out to evaluate the efficacy of intraventricular
      sodium nitroprousside (SNP) in the reversal of refractory vasospasm secondary to
      aneurysmal subarachnoid hemorrhage (SAH). Ten patients of aneurysmal SAH with
      symptomatic vasospasm, corroborated on Transcranial Doppler (TCD) and/or
      angiography, were included in the study. The mean age distribution of the
      patients was 50.8 years (range 33-65 years) with an equal number of males and
      females. Once vasospasm was refractory even after 12 hours of SAH therapy,
      intraventricular SNP was instilled in an escalating dose and the reversal of
      vasospasm was monitored on TCD and/or angiography. All patients showed
      improvement in TCD velocity on day 0 through day 3. Partial to complete reversal
      of vasospasm was demonstrated on angiography in all the patients, though not in
      all the vessels. Two patients who had weakness of limbs due to vasospasm improved
      following intraventricular SNP therapy. Vomiting was the commonest adverse effect
      (7/10). Three patients had mild fluctuation in blood pressure. The overall
      outcome was good in 6 out of 10 patients. The study suggests that
      intraventricular SNP therapy is effective in reversing the changes even in
      established cases of SAH-induced vasospasm.

PMID- 14571003
TI  - Ventilatory management of respiratory failure in patients with severe Guillain
      Barre syndrome.
AB  - Guillain-Barre syndrome (GBS) is the commonest peripheral neuropathy causing
      ventilatory failure, and 10-30% patients may require respiratory support. Records
      of 11 adult patients of GBS in respiratory failure, admitted to the Respiratory
      Intensive Care Unit (RICU) of our institute for mechanical ventilation over a
      four-year period, were studied. Six patients received intravenous immunoglobulin.
      The median duration of mechanical ventilation was 38 days. Seven patients
      underwent tracheostomy. Four patients were ventilated for less than 2 weeks and 3
      for more than 2 months each. Seven developed ventilator-associated pneumonia
      and/or sepsis. Three patients died in, and two shortly after discharge from RICU;
      all had systemic problems or complications of hospitalization.

PMID- 14571004
TI  - Three-dimensional CT angiography in the evaluation of cerebral arteries in acute
      hemorrhage.
AB  - OBJECTIVE: We conducted this study to demonstrate the value of non-invasive three
      dimensional CT angiography (3D CTA) in the detection of a cerebral aneurysm.
      MATERIAL AND METHODS: A helical CT acquisition was obtained using non-ionic
      contrast media in 50 patients with 1 mm per second table speed, 1 mm collimation,
      and pitch 1:1. Axial source images were transferred into a workstation console
      (Advantage windows GE) and CTA was obtained using MIP (Maximum Intensity
      Projection) reconstruction. Fourteen patients underwent conventional digital
      subtraction angiography (DSA) after 3D CTA prior to surgery. RESULTS: A total of
      39 aneurysms were detected in 50 patients. All patients with an aneurysm were
      operated and the presence of aneurysms was confirmed. 3D CTA detected 38 of these
      39 aneurysms. In 37 aneurysms, the origin of the aneurysm and aneurysm neck was
      adequately visualized. 3D CTA was found to be 100% specific and 97.2% sensitive
      in picking up cerebral aneurysms. 3D CTA was 97% specific in demonstrating the
      exact origin and showing the neck of the aneurysm. CONCLUSIONS: CT angiography is
      a simple, quick, and non-invasive technique and can replace DSA in most patients
      with acute subarachnoid hemorrhage aneurysm for the detection and
      characterization of aneurysms of the circle of Willis. The relation of the
      aneurysm with bony landmarks was clearly depicted.

PMID- 14571005
TI  - Nadroparin plus aspirin versus aspirin alone in the treatment of acute ischemic
      stroke.
AB  - Low-molecular-weight-heparin (LMWH) has been widely used in the treatment of
      acute ischemic stroke but controlled trials are few. In this study, 40 patients
      with acute ischemic stroke of less than 24 hours duration were randomized to
      receive either aspirin (325 mg/day) alone or aspirin (325 mg/day) plus
      subcutaneous nadroparin 4100 units/day. At the end of 4 weeks, the morbidity and
      mortality were significantly less in the nadroparin group as compared to the
      aspirin group. There was no increased risk of clinically significant intracranial
      hemorrhage in either group. The combination of aspirin and LMWH deserves to be
      tested in larger studies.

PMID- 14571006
TI  - Changes in the isoprenoid pathway with transcendental meditation and Reiki
      healing practices in seizure disorder.
AB  - A quantal perceptive model of brain function has been postulated by several
      groups. Reiki-like healing practices in seizure disorder (ILAE classification-II
      E-generalized seizures-tonic clonic), involving transfer of life force or low
      level of electromagnetic force (EMF) from the healer to the recipient patient,
      may act via quantal perceptive mechanisms. Increased synthesis of an endogenous
      membrane Na+-K+ ATPase inhibitor digoxin and a related tyrosine / tryptophan
      transport defect has been demonstrated in refractory seizure disorder (ILAE
      classification-II E-generalized seizures-tonic clonic). Reiki-like healing
      practices in refractory epilepsy results in a reduction in seizure frequency.
      Reiki-like healing practices produce membrane stabilization and stimulation of
      membrane Na+-K+ ATPase activity by quantal perception of low levels of EMF. The
      consequent intracellular hypermagnesemia inhibits HMG CoA reductase activity and
      digoxin synthesis resulting in the alteration of the neutral amino acid transport
      (tryptophan / tyrosine) defect. A hypothalamic digoxin-mediated quantal
      perception model of brain function is proposed. The phenomena of biological
      transmutation and consequent hypermagnesemia occurring in the resultant neuronal
      quantal state is also discussed.

PMID- 14571007
TI  - Missile injuries of the brain: results of less aggressive surgery.
AB  - Sixty cases of missile injuries (59 males, average age 25 years) were studied
      over a period of one year. Forty-three patients had suffered splinter injuries,
      12 had gunshot wounds and 5 had suffered injuries from improvised explosive
      devices. The Glasgow coma scale was <5 in 8 patients, 5-8 in 14, 8-12 in 30 and
      13-15 in 8 patients. Extensive comminution of skull bones was found in 10
      patients. Thirty-five patients had penetration of the skull and the rest had
      orbito-cranial or facio-cranial wounds. CT scan revealed small hemorrhagic
      contusion with in-driven bones without mass effect in 15, contusion with mass
      effect in 36 cases, cortical contusions without in-driven bones (tangential
      injuries) in 3, distant intracranial contusions in 4, intraventricular
      hemorrhages in 5, multilobar injuries in 14, and unilobar injury in 40. Fifty-two
      patients were operated upon at our center, of which 30 were operated within 24
      hrs, 10 between 24 to 48 hrs, and 12 between 48 to 72 hrs. Six patients were
      treated conservatively and 2 underwent only a simple closure of scalp wound.
      Craniectomy was done in 10 and craniotomy in 42 patients. Two patients developed
      wound sepsis, one had aspiration pneumonia, one had septicemia and one had deep
      vein thrombosis while one had post-traumatic hydrocephalus. On follow-up at 6
      months, the outcome as per the Glasgow outcome scale was as follows: Good outcome
      in 42, moderate disability in 7, severe disability in 6 and death of 5 patients.
      Retained bone fragments were found in 36.3 % on follow-up CT scan but no one had
      brain abscess.

PMID- 14571008
TI  - Plasma antioxidant vitamins in brain tumors.
AB  - Plasma levels of vitamins A, E and C were analyzed in 102 patients with different
      types of brain tumors. A follow-up study was done with 27 postoperative patients.
      On comparison with plasma from normal individuals, vitamin A and E were
      decreased, but the decrease was statistically insignificant. Vitamin C levels
      remained in the normal range. In a comparative study of preoperative and
      postoperative cases, plasma vitamin A levels in postoperative glioma patients
      were significantly higher than those in the pre-operative state. There was no
      significant difference in the plasma level of vitamins C and E. The results of
      the present study suggest that the plasma antioxidant vitamins are not altered
      effectively in brain tumor cases.

PMID- 14571010
TI  - Primary degenerative cerebellar ataxias in ethnic Bengalees in West Bengal: some
      observations.
AB  - Seventy cases of primary degenerative cerebellar ataxias in ethnic Bengalees from
      southern West Bengal, India, were studied by the authors. Of these, 50 cases were
      of the familial type (hereditary ataxias) encountered in 23 families and the
      remaining 20 were of sporadic onset. 18 cases (from 11 families) were of
      "probable" autosomal recessive (AR) inheritance, 12 cases (8 families) had
      Friedreich's type ataxia (FA), 4 cases (2 families) had FA type ataxia with
      retained reflexes and in 2 cases (1 family) the exact phenotypic characterization
      could not be made. AR inheritance in these cases seemed most likely in view of
      the occurrence in a single generation with unaffected parents and history of
      consanguinity in many of the families studied. Genotypic confirmation of FA type
      ataxia and its variants could not be done in any case due to the non-availability
      of technology for studying the FA locus but some common dominant ataxia genotypes
      could be excluded. Thirty-two cases (from 12 families) with autosomal dominant
      ataxias (ADCA) were studied. Genotype analysis revealed 4 families with SCA2
      genotype, 5 families with SCA3 and 3 families where genotypic characterization
      could not be made (phenotypically 2 were of ADCA I and 1 of ADCA II). No clear
      preponderance of one particular genotype of SCA over another could be
      demonstrated in our ethnic Bengalee patients. We also noted significant intra and
      inter-family variations in phenotypes within the same genotypic form as well as
      overlapping of clinical signs between different genotypes. Slow saccades and
      peripheral neuropathy were not seen consistently in our ethnic Bengalee subjects
      with SCA2 genotype. Similarly, extrapyramidal features, ophthalmoplegias and
      distal amyotrophy were seen in some but not all families with the SCA3 genotype.
      Phenotypic expression appeared to be an inconsistent marker of the SCA genotype
      in our patients. Of the 20 sporadic cases with cerebellar ataxia, genotype
      analysis revealed 2 cases with SCA1 and 1 with SCA2. Some of the sporadic ataxia
      cases had extracerebellar involvement and may warrant classification as Multiple
      System Atrophy. In all the 3 subjects with genotype characterization, phenotype
      correlation was lacking. The clinical pattern of hereditary ataxias in ethnic
      Bengalees seems to be somewhat different from that seen in Western India. The
      need for clinical and genetic studies of ataxias in different specific ethnic
      populations of India has been stressed.

PMID- 14571009
TI  - Deletion analysis of the dystrophin gene in Duchenne and Becker muscular
      dystrophy patients: use in carrier diagnosis.
AB  - The dystrophin gene was analyzed in 8 Duchenne muscular dystrophy (DMD) and 10
      Becker muscular dystrophy (BMD) unrelated families (22 subjects: 18 index cases
      and 4 sibs) for the presence of deletions by multiplex polymerase chain reaction
      (mPCR; 27 exons) and Southern hybridization using 8 cDMD probes. Deletions were
      identified in 5 DMD and 7 BMD patients (6 index cases and 1 sib). The concordance
      between the clinical phenotype and "reading frame hypothesis" was observed in
      11/12 patients (92%). The female relatives of DMD/BMD patients with identifiable
      deletions were examined by quantitative mPCR. Carriers were identified in 7
      families. We also describe a variation in the HindIII pattern with cDNA probe 8
      and 11-14. Molecular characterization of the dystrophin gene in this study has
      been helpful in advising the patients concerning the inheritance of the
      condition, and carrier diagnosis of female relatives, and should also prove
      useful for prenatal diagnosis.

PMID- 14571011
TI  - Relevance of computerized electroencephalographic topography (brain mapping) in
      ischemic stroke.
AB  - BACKGROUND AND AIMS: Computerized electroencephalographic topography (CET) (brain
      mapping) is a non-invasive, spatially oriented procedure for depicting amplitude
      and frequency patterns by two-dimensional color-coded frequency and amplitude
      display of the electroencephalograph (EEG). MATERIAL AND METHODS: We
      prospectively studied the relationship between CT scan lesions, conventional EEG
      and brain mapping in 40 patients with ischemic stroke within 1 week of onset. EEG
      and brain mapping was done within 24 hours of doing CT scan. RESULTS: There were
      32 males and 8 females and the mean age was 56 years (range 27-75 years). CET/EEG
      was normal in 2 patients with capsular infarct. Brain mapping showed
      abnormalities (most commonly low-frequency high-amplitude changes) in 95% of
      patients, whereas EEG abnormalities were seen in only 40%. Brain mapping
      abnormalities were appropriate to the side of the CT scan lesion in 20 (52.63%)
      patients and were present bilaterally n 18 (47.37%) patients. Brain mapping
      abnormalities were ipsilateral to the side of the CT lesion when the lesion was <
      2 cm in diameter and they were bi-hemispherical when the CT lesion was > 2 cm in
      diameter. CONCLUSIONS: There was no correlation between motor deficits and brain
      map abnormalities.

PMID- 14571012
TI  - Association of primary central nervous system lymphomas with the Epstein-Barr
      virus.
AB  - The incidence of primary central nervous system lymphoma (PCNSL), previously a
      rare tumor, has increased significantly over the past few decades, partly due to
      the AIDS epidemic but also in immunocompetent individuals. Studies from Western
      countries have shown a consistent association of tumors occurring in
      immunocompromised individuals with the Epstein-Barr virus (EBV) suggesting an
      important role for the virus in the pathogenesis of these tumors, but an
      infrequent association of the virus with PCNSL in the immunocompetent host has
      also been noted. We studied 11 patients with PCNSL who had no evidence of an
      immunocompromised state. All the tumors were aggressive B cell lymphomas. EBV
      association was studied using EBER in-situ hybridization. 10 out of the 11 tumors
      were negative for EBV, indicating that tumors in immunocompetent individuals in
      developing countries are also infrequently EBV associated and that a different
      pathogenetic mechanism is operative in the evolution of these tumors.

PMID- 14571013
TI  - Prevalence of photosensitivity--an Indian experience.
AB  - One thousand nine hundred and forty newly recruited entrants for training as
      pilots (Group A) underwent photic stimulation during EEG recording during the
      entrance examination to the flying stream. One hundred and sixty individuals
      (Group B) working on radars for prolonged periods were interviewed for eliciting
      complaints referable to photosensitivity and were subjected to EEG. EEGs in
      respect to 1000 cases (Group C) of known epilepsy were examined for the incidence
      of a photosensitive response. The study has revealed that 14 cases (0.72%) in
      group A had an abnormal response to photic stimulation out of which one case
      developed seizure during EEG recording. One case (0.62%) in group B and 30 cases
      (3%) in group C were detected to have photosensitivity. The maximum response was
      seen at 20 Hz stimulation. The prevalence of photosensitivity and its
      manifestations in these groups indicates that this condition is not uncommon.

PMID- 14571014
TI  - Acute onset paraneoplastic cerebellar degeneration in a patient with small cell
      lung cancer.
AB  - A patient with small cell lung cancer presented with a rare presentation of an
      acute onset pancerebellar dysfunction. His clinical condition markedly improved
      following the surgical removal of the tumor and chemo- and radiotherapy.

PMID- 14571015
TI  - Cerebellar hemisphere, an uncommon location for pleomorphic xanthoastrocytoma and
      lipidized glioblastoma multiformis.
AB  - Lipidized glioblastoma multiformis (LGB) and pleomorphic xanthoastrocytoma (PXA)
      are often supratentorial in location and occur in the second to fourth decade.
      This report presents two young patients, one having LGB and the other having PXA
      in the cerebellum. Histological differentiation between LGB and PXA is discussed.

PMID- 14571016
TI  - Extranasal glial heterotopia: case report.
AB  - Glial heterotopia or the occurrence of isolated non-teratomatous extracranial
      glial tissue is rare. We report a neonate with extensive extranasal glial
      heterotopia involving the left buccopharyngeal region, palate and base of the
      skull and presenting with respiratory distress and a bleeding oral mass. A staged
      operative approach was adopted to excise the lesion. The literature on the
      subject is briefly reviewed.

PMID- 14571017
TI  - Congenital absence of the posterior elements of C2 vertebra: a case report.
AB  - A rare case of the complete absence of the posterior elements of C2 is reported.
      The patient presented with neck pain without any neurological deficits and
      radiology revealed a mobile, partially reducible dislocation of the C2 over C3
      vertebra. A posterior fusion utilizing a contour rod, sublaminar wire fixation,
      and onlay bone grafts between the occiput and the C3 vertebra was performed for
      spinal stability.

PMID- 14571018
TI  - Patient with limb girdle dystrophy presenting with dopa-responsive dystonia--a
      case report.
AB  - Dopa-responsive dystonias are rare. We report a 14-year-old male who was
      diagnosed as a case of limb girdle dystrophy and had features suggestive of dopa
      responsive dystonia.

PMID- 14571019
TI  - Akathisia--diagnostic dilemma and behavioral treatment.
AB  - Akathisia, an involuntary movement disorder resulting from exposure to
      antipsychotics, is characterized by subjective restlessness and a strong desire
      to move about. The diagnosis is often complicated by the overlapping symptoms of
      pseudoakathisia, chronic akathisia and tardive dyskinesia. This report deals with
      a patient with schizophrenia who developed akathisia after exposure to
      antipsychotics. Later, she developed movements that were more like
      pseudoakathisia and tardive dyskinesia rather than acute akathisia. On failure of
      anti-akathisia medication, she was treated with a behavioral regime to which her
      akathisia responded. This behavioral regime used the technique of distraction as
      a primary tool. This case report highlights the diagnostic difficulties in
      akathisia and the application of behavioral treatment for akathisia that is non
      responsive to anti-akathisia medication.

PMID- 14571020
TI  - Two siblings with Allgrove's syndrome and extrapyramidal features.
AB  - We report two siblings with Allgrove's syndrome and extrapyramidal features.
      Though various neurological abnormalities have been described in this disorder,
      we report the first patient of Allgrove's syndrome associated with dystonia and
      chorea.

PMID- 14571021
TI  - Giant cell reparative granuloma of the base of the skull presenting as a
      parapharyngeal mass.
AB  - Giant cell reparative granuloma is an infrequent non-tumoral lesion affecting the
      maxillary and mandibular bones and only rarely, the cranial bones. We report a
      case of giant cell reparative granuloma of the base of the skull in a 12-year-old
      female who presented with a parapharyngeal mass. Computerized Tomography (CT)
      showed the intracranial extension and destruction of surrounding bones.

PMID- 14571022
TI  - Simultaneous occurrence of multiple meningiomas in different neuraxial
      compartments.
AB  - The simultaneous occurrence of multiple meningiomas in different neuraxial
      compartments is rare. A 35-year-old female patient had multiple meningiomas
      involving both the supratentorial compartments and in the upper dorsal spine. The
      patient underwent excision of 2 cranial and 2 spinal meningiomas, and has
      remained asymptomatic over a follow-up period of 18 months.

PMID- 14571023
TI  - Post-cardiorespiratory arrest beta-alpha coma: an unusual electroencephalographic
      phenomenon.
AB  - The presence of frontally-dominant alpha pattern in the EEG is common in patients
      with coma due to trauma, toxic-metabolic causes and following cardiorespiratory
      arrest. Diffuse beta activity following resuscitation after a cardiac arrest is
      not well recognized. We report a case of coma in a 3-year-old girl who had a
      cardiac arrest from which she was revived. Initial EEG showed diffuse beta
      activity, which later evolved to predominantly alpha activity. The possible
      mechanisms involved in the generation of such rhythms are discussed. Transition
      of EEG activity from faster to slower frequencies is suggested as an adverse
      prognostic factor in post-cardiorespiratory arrest coma.

PMID- 14571024
TI  - Laparoscopic management of complicated ventriculoperitoneal shunts.
AB  - Intra-abdominal migration of the catheter and formation of a cerebrospinal fluid
      pseudocyst are both rare complications of a ventriculoperitoneal shunt.
      Traditionally, each condition is treated by a formal laparotomy. Laparoscopic
      management of the complications in two patients is described.

PMID- 14571025
TI  - Internuclear ophthalmoplegia and torsional nystagmus: an MRI correlate.
AB  - The association of internuclear ophthalmoplegia (INO) with torsional nystagmus is
      rare. We report a case of a 72-year-old male who developed brainstem stroke and
      was found to have left INO with torsional nystagmus. An MRI correlation in this
      case has been described.

PMID- 14571026
TI  - Rhabdoid tumor of the thalamus.
AB  - Rhabdoid tumors of the central nervous system are uncommon tumors. About 188
      cases have been reported in the literature so far. In this report, we describe a
      case of a rhabdoid tumor of the thalamus in a 35-year-old male patient. Light
      microscopic and immunohistochemical features are discussed and the relevant
      literature reviewed.

PMID- 14571027
TI  - Liponeurocytoma of the cerebellum--a case report.
AB  - We report the characteristic neuropathological features of a rare case of
      cerebellar liponeurocytoma in a 62-year-old female. The tumor has a low
      proliferative potential and carries a favorable prognosis.

PMID- 14571028
TI  - Cytodiagnosis of anaplastic astrocytoma with metastasis to the cerebrospinal
      fluid in a neonate--a case report.
AB  - A case of left cerebral hemispheric anaplastic astrocytoma with metastasis to the
      cerebrospinal fluid in a 50-day-old male child diagnosed on cytology and later
      confirmed by histological examination is reported.

PMID- 14571029
TI  - The significance of corpora amylacea in mesial temporal lobe epilepsy.
AB  - Temporal lobe epilepsy (TLE) associated with mesial temporal sclerosis (MTS),
      mesial TLE (MTLE), is the commonest medically refractory adult epilepsy syndrome.
      Corpora amylacea (CoA) have been shown to be a marker of MTS. We compared 9
      patients with MTS who had dense deposition of CoA in their hippocampi with 25
      patients with MTS who did not have CoA. The patients with CoA were significantly
      older and they showed a trend towards having a significantly longer duration of
      epilepsy. The postoperative seizure outcome at 2 years was not different in the 2
      groups. Our results could indicate the progressive nature of the pathology of
      MTS, probably indicating excitotoxic damage due to recurrent seizures, but they
      need to be verified by clinicopathological correlation among a larger number of
      patients with MTLE.

PMID- 14571031
TI  - Management of ocular myasthenia gravis coexisting with thyroid ophthalmopathy.

PMID- 14571030
TI  - Holoprosencephaly with cyclopia--report of a pathological study.
AB  - A rare case of a lobar holoprosencephaly with cyclopia, associated with non
      nervous system anomalies is being reported.

PMID- 14571032
TI  - Recurrent Miller Fisher syndrome.

PMID- 14571036
TI  - Predicting long-term morbidity in Indian patients with ischemic stroke.

PMID- 14571035
TI  - Pseudotumour cerebri and Guillain-Barre syndrome: cause or effect?

PMID- 14571037
TI  - Germinoma of the pineal gland.

PMID- 14571039
TI  - Osteoma mimicking a partly calcified meningioma.

PMID- 14571040
TI  - Cerebellopontine angle epidermoid tumor presenting with hemifacial spasms.

PMID- 14571041
TI  - Cavernous sinus syndrome due to syphilitic pachymeningitis.

PMID- 14571042
TI  - Unusual neurological complications in a case of organophosphate poisoning.

PMID- 14571043
TI  - Acute epidural hematoma following twist-drill craniostomy for chronic subdural
      hematoma--a rare complication.

PMID- 14571044
TI  - Congenital cholesteatoma.

PMID- 14571045
TI  - A case of acute flaccid paralysis as an unusual presentation of serum sickness.

PMID- 14571046
TI  - Primary cranial vault non-Hodgkin's lymphoma.

PMID- 14571047
TI  - Spontaneous evacuation of cerebellar abscess through the middle ear.

PMID- 14571048
TI  - Surgery for multiple intracranial hydatid cysts.

PMID- 14571049
TI  - Multifocal intracranial rhabdoid tumor.

PMID- 14571050
TI  - Psychopathological symptoms of depression in Parkinson's disease compared to
      major depression.
AB  - Parkinson's disease is frequently associated with depressive symptoms. When
      depression occurs at early stages and before the onset of characteristic motor
      symptoms of the disease, differential diagnosis of major depression may be
      difficult. Differences in psychopathological features of depression in
      Parkinson's disease and major depression have been reported by some authors. This
      study presents data of 49 patients with depression in Parkinson's disease and 38
      patients with major depression. The severity of depressive symptoms was
      equivalent in both groups. Depressive features did not differ between the two
      groups with exception of affective flattening, delusional ideas and suicide
      attempts. In conclusion, this investigation gives support to the assumption of a
      common neurobiological origin of depression in Parkinson's disease and major
      depression.

PMID- 14571051
TI  - The five symptom dimensions and depression in schizophrenia.
AB  - The aim of this study was to investigate the relationship between the five-factor
      model of psychopathology and depression in schizophrenia. Symptoms were rated
      using the Positive and Negative Syndrome Scale (PANSS) and the Montgomery and
      Asberg Depression Rating Scale (MADRS) in 105 chronic patients with
      schizophrenia. Principal-component analysis (PCA) produced a five-factor solution
      for the PANSS (psychomotor poverty, disorganisation, reality distortion,
      excitement, and depression), and a two-factor solution for the MADRS
      (psychological and behavioural depression). The PANSS depression factor was
      highly associated with the MADRS psychological depression factor but not with
      MADRS behavioural depression. By contrast, the PANSS excitement factor showed a
      strong positive correlation with the behavioural depression factor but not with
      psychological depression. These MADRS factors were not associated significantly
      with the core PANSS factors, including psychomotor poverty. It is suggested that
      depression exists as an independent domain, differentiated from negative
      symptoms, in the structure of schizophrenia symptomatology.

PMID- 14571052
TI  - Risk factors associated with childbearing-related episodes in women with bipolar
      disorder.
AB  - OBJECTIVE: For the onset of illness and possible recurrence during the
      childbearing period, women with bipolar disorder (BD) are at a higher risk. The
      aim of this study was to evaluate the impact of clinical and psychosocial factors
      associated with pregnancy and the postpartum period on the course of BD. METHODS:
      The childbearing and illness history of 72 women with BD were assessed to
      determine mood episodes related to the childbearing period. Data was analyzed to
      evaluate the risk factors (clinical, obstetric and psychosocial factors) related
      with mood episodes during pregnancy and the postpartum period. RESULTS: Data of
      252 pregnancies and childbirths of 72 women with BD were included in the
      analysis. Twenty-three (32%) women with BD reported at least one mood episode
      during pregnancy or within 1 month after childbirth (childbearing-related
      episode, CBRE). Subjects with CBREs mean age at onset of illness and mean age at
      the time of assessment were significantly younger than subjects with N-CBRE. A
      lower number of women who experienced a postpartum episode after the birth of the
      first child chose to have the second one. Psychosocial factors during pregnancy
      and the postpartum period and method of delivery did not predict the first
      postpartum episode. Onset of illness at an early age, experiencing episode during
      the first pregnancy and experiencing physical problems during pregnancy predicted
      a mood episode during the first postpartum period. CONCLUSIONS: Interpretation of
      the results of the study is limited with the retrospective nature of data
      collection. Within the limitations, we may suggest that psychosocial factors do
      not play a significant role in the genesis of CBREs in women with BD.

PMID- 14571053
TI  - Body image disturbance, parental bonding and alexithymia in patients with eating
      disorders.
AB  - BACKGROUND: To evaluate if body image disturbance and alexithymia, two major
      clinical features of eating disorders (ED), are predicted by an altered parental
      bonding. SAMPLING AND METHODS: 64 female ED outpatients and 68 female healthy
      controls were assessed by means of the Parental Bonding Instrument (PBI), the
      Body Uneasiness Test (BUT), and the Toronto Alexithymia Scale (TAS-20). Pearson's
      correlations and multiple stepwise regression analysis were applied to explore
      the contribution of PBI factors on BUT and TAS scores. RESULTS: BUT weight
      phobia, body image concerns, avoidance, depersonalization, Global Severity Index
      and positive symptom total were predicted by low parental care, while compulsive
      self-monitoring was predicted by parental overprotection. TAS total score and
      difficulty in describing feelings were predicted by low maternal care.
      CONCLUSIONS: Body image disturbance in ED may be conceptualized as a deficit in
      self-development, resulting from failures in parent-child interactions which
      impaired the ability to distinguish bodily needs from emotional experiences.

PMID- 14571054
TI  - Eating disorders and body image disturbances among ballet dancers, gymnasium
      users and body builders.
AB  - BACKGROUND: Eating disorders are frequent among elite performers of certain
      sports or physical activities; however, little is known about non-professional
      performers. METHOD: 113 female non-elite ballet dancers, 54 female gymnasium
      users, 44 male non-competitive body builders, 105 female controls and 30 male
      controls were evaluated using the Body Uneasiness Test, the State-Trait Anxiety
      Inventory, the Beck Depression Inventory, and the Eating Disorder Examination
      12th edition (EDE-12). RESULTS: Non-elite ballet dancers reported the highest
      prevalence of eating disorders (anorexia nervosa 1.8%; bulimia nervosa 2.7%;
      eating disorders not otherwise specified 22.1%), followed by gymnasium users
      (anorexia nervosa 2.6%; eating disorders not otherwise specified 18%).
      Significant differences (p < 0.01) between athletes and their controls were found
      in the following parameters (median values): Beck Depression Inventory (female
      dancers 5.7, gymnasium users 6.1, female controls 2.8, body builders 1.6, and
      male controls 1.3), Body Uneasiness Test (female dancers 1.08, gymnasium users
      0.62, female controls 0.54, body builders 0.35, and male controls 0.27), EDE
      total scores (female dancers 1.6, gymnasium users 1.7, female controls 1.0, body
      builders 1.0, and male controls 0.4), EDE - restraint subscale scores (female
      dancers 0.8, gymnasium users 1.6, female controls 0.0, body builders 0.8, and
      male controls 0.0), EDE--eating concern subscale scores (female dancers 0.4,
      gymnasium users 0.2, female controls 0.0, body builders 0.0, and male controls
      0.0), EDE--weight concern subscale scores (female dancers 2.1, gymnasium users
      2.1, female controls 1.6, body builders 1.4, and male controls 0.5), and EDE-
      shape concern subscale scores (female dancers 2.7, gymnasium users 2.8, female
      controls 2.0, body builders 2.1, and male controls 0.9). EDE scores were highly
      related to Body Uneasiness Test scores, especially in non-elite ballet dancers
      and in non-competitive body builders (p < 0.01). CONCLUSION: Non-professional
      performers of sports emphasising thinness or muscularity, such as ballet and body
      building, show a high degree of body uneasiness and inappropriate eating
      attitudes and behaviours.

PMID- 14571055
TI  - Quality of life in anxiety disorders: a comparison of obsessive-compulsive
      disorder, social anxiety disorder, and panic disorder.
AB  - BACKGROUND: There is growing recognition that the anxiety disorders are disabling
      disorders associated with substantial morbidity and impaired quality of life
      (QOL). Nevertheless, there have been few studies comparing QOL across these
      conditions. SAMPLING AND METHODS: 337 outpatients with obsessive-compulsive
      disorder (OCD; n = 220), panic disorder (PD; n = 53), or social anxiety disorder
      (SAD; n = 64) were compared using a number of assessment scales to compare
      objective and subjective impairment in QOL. The association of QOL with symptom
      severity and comorbid depression was also assessed. RESULTS: The extent of
      impairment due to OCD, PD or SAD appears to be similar across the QOL scales.
      However, various domains are differentially affected in each of the disorders;
      OCD patients had more impairment in family life and activities of daily living;
      SAD patients had more impairment in social life and leisure activities, and PD
      patients were less able to avoid the use of nonprescribed drugs. QOL was lower in
      patients with increased symptom severity as well as in those with comorbid
      depression. CONCLUSIONS: While the extent of impairment appears similar across a
      number of different anxiety disorders, characteristic symptoms of each disorder
      may be associated with differential impairment of various domains of function,
      and may require specifically tailored interventions.

PMID- 14571056
TI  - Dissociation between inattentiveness during mental status testing and social
      inattentiveness in the Scale for the Assessment of Negative Symptoms attention
      subscale.
AB  - The Scale for the Assessment of Negative Symptoms (SANS) attention subscale has
      been found valid and reliable by some studies; however, there is some evidence to
      the contrary. We hypothesized that social inattentiveness (SANS 22) and
      inattentiveness during mental status testing (SANS 23) might be describing
      discrete constructs, and this dissociation might be a source of controversy.
      Thirty-five patients with DSM-IV schizophrenia were assessed by the Scale for the
      Assessment of Positive Symptoms (SAPS), SANS and a neuropsychological battery.
      The 2 attention items were not significantly interrelated. SANS 22 was correlated
      with bizarre behavior and alogia, and none of the neuropsychological test scores,
      whereas SANS 23 showed strong correlations with the Wechsler Memory Scale mental
      control subscore, total errors on the Benton Revised Visual Retention Test, and
      the information, similarities and the general verbal subscores on the Wechsler
      Adult Intelligence Scale. Regression analyses showed that SANS 23 could be a good
      estimate of general verbal abilities. These findings point to a dissociation
      between the 2 SANS attention items. Similar analyses should be repeated in larger
      and heterogeneous samples and include a factor analysis of the individual items
      rather than the global ratings.

PMID- 14571057
TI  - The quality of interactions between staff and psychiatric inpatients in a
      Nigerian general hospital.
AB  - We examined the quality of the staff's interactions with patients, and its
      relationship with ward structure, patients' satisfaction and outcome. The Quality
      of Interactions Schedule was used to observe interactions with patients in two
      acute admission wards. In 40 h, 101 interactions were observed; 60.4% were of
      negative quality, 35.6% were positive and 3.9% were neutral. The majority (42.6%)
      were of the negative restrictive type, with the patients' freedom being curtailed
      without explanation. Significantly more interactions occurred at the proximal
      sections of the wards, where most ward activities took place. There were no
      significant gender and interward differences. Interactions were not associated
      with clinical outcome. The patients were significantly not satisfied with the
      items that related to the curtailment of their freedom. They are sensitive to the
      quality of staff interactions while appreciating staff contribution to their
      care. Training programs should include staff attitudes for the improvement of the
      overall quality of care.

PMID- 14571058
TI  - Delusion of pregnancy. A case report and review of the literature.
AB  - This case report describes the longstanding course of a delusion of pregnancy in
      a 51-year-old schizophrenic Ghanaian woman suffering from multiple symptoms of
      delusions and hallucinations. In addition to these symptoms, the patient was
      affected by multiple coenesthesias, ego disturbances and bizarre delusions of
      being influenced by external forces. A multi-causal aetiology of delusional
      pregnancy is discussed.

PMID- 14571059
TI  - A parametric approach to the phonetics of postvocalic /r/ in Dutch.
AB  - This paper describes the phonetic exponents of rhoticity in postvocalic position
      in the speech of 4 young adult speakers of Standard Dutch. In addition to
      describing aspects of the segmental realisation of /r/, the paper focusses on
      parametric differences between rhymes with and without postvocalic /r/ in the
      material under consideration, presenting both impressionistic observations and
      instrumental measurements. Results of the investigation suggest that parametric
      analysis is a crucial complement to segmental classification, in providing
      insights into the relation between segmental realisations and 'contextual
      effects' of /r/, the phonetics of /r/ deletion and similarities and differences
      between rhotics cross-linguistically.

PMID- 14571060
TI  - The effect of local speaking rate on the perception of quantity in Estonian.
AB  - The Estonian language with its elaborate system of contrasts in quantity, whose
      essentials are described in the paper, is used to investigate human perception of
      distinctive contrasts in the duration of vowels, consonants and larger units. In
      the experiments reported, the speaking rate of a preceding or following syllable
      was manipulated in addition to that of a target V, C or VC sequence that carried
      a quantity distinction in disyllabic words. The results confirmed that the second
      syllable in such words, in particular the duration of its vowel, serves as a
      reference, but they showed segments of additional syllables to contribute in the
      same direction. The results provided no support for ascribing quantity to any
      larger units than phonetic segments. Speech rate effects of similar magnitude
      have been observed in Japanese, while effects of the same kind were found to be
      smaller in Dutch. These differences may be linked with the functions durational
      contrasts have in the different languages. It appears that listeners have to
      adapt more fully to variations in the local speaking rate when there are no
      additional cues and the functional load of quantity distinctions is high.

PMID- 14571061
TI  - The interplay of speech perception and phonology: experimental evidence from
      Turkish.
AB  - This study supports claims of a relationship between speech perception and
      phonology with evidence from a crosslinguistic perception experiment involving
      /h/ deletion in Turkish. Turkish /h/ is often deleted in fast speech, but only in
      a specific set of segmental contexts which defy traditional explanation. It is
      shown that /h/ deletes in environments where lower perceptibility is predicted.
      The results of the perception experiment verify these predictions and further
      show that language background has a significant impact on speech perception.
      Finally, this perceptual account of Turkish /h/ deletion points to an empirical
      means of testing the conflicting hypotheses that perception is active in the
      synchronic grammar or that its influence is limited to diachrony.

PMID- 14571062
TI  - What is poikiloderma?

PMID- 14571063
TI  - The pigmented and purpuric dermatitis and the many faces of mycosis fungoides.

PMID- 14571064
TI  - Skin weathering: the face at the interface.

PMID- 14571065
TI  - Do human papillomaviruses target epidermal stem cells?
AB  - Little is known about the target cells of human papillomaviruses (HPVs). The
      clinical and histological analyses of very early lesions of palmoplantar warts
      indicate that not only the warts initially developed exclusively in the ridges of
      the skin, but also that the initial histological changes were restricted to the
      deep ridges of the epidermis, where epidermal stem cells are thought to exist in
      the palmoplantar skin. This suggests that HPV infection targets the stem cells.

PMID- 14571066
TI  - Treatment failures and relapses in onychomycosis: a stubborn clinical problem.
AB  - The therapeutic outcome of onychomycoses is uncertain. Comparative short-term
      efficacy studies on antifungals abound and report contradictory findings. Few
      unbiased follow-up studies have scrutinized the long-term outcome. Basically,
      none of the current antifungals can guarantee cure in all instances. In addition,
      relapses are not rare. The causes of therapeutic failure in onychomycoses are
      multiple. The most important are the lack of diagnostic accuracy, inadequate
      antifungal choice or delivery modality, and presence of dormant conidia,
      sequestrated mycelium pockets or resistant fungal species. The concept of
      fungicidal drug derived from selected in vitro studies appears irrelevant in
      clinical practice.

PMID- 14571067
TI  - High iron and low ascorbic acid concentrations in the dermis of atopic dermatitis
      patients.
AB  - BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease in
      which reactive oxygen species (ROS) may be involved. Iron catalyses ROS formation
      and ascorbic acid (AA) scavenges these species. OBJECTIVE: The aim of this work
      was to determine iron and AA levels in AD patients' dermis and to compare their
      concentrations with those of healthy volunteers' dermis. METHODS: Five AD
      patients and 5 healthy subjects (controls) were enrolled in this study. Iron and
      AA were collected from human dermis by microdialysis and assessed by atomic
      absorption spectrometry and gas chromatography-mass spectrometry, respectively.
      RESULTS: The AD dermis demonstrated higher iron concentrations (44.3 +/- 4.6
      microg/l) compared to controls (21.8 +/- 1.2 microg/l) as well as a significantly
      lower concentration of AA (46.7 +/- 0.6 vs. 176.8 +/- 14.5 microg/ml,
      respectively). CONCLUSION: These results suggest that iron and AA dermis levels
      could be indicators of inflammatory tissues and might be implicated in
      dermatological diseases such as AD.

PMID- 14571068
TI  - Estrogen dermatitis: a dendritic-cell-mediated allergic condition.
AB  - BACKGROUND: Most estrogen dermatitides are induced by local or systemic contact
      dermatitis where dendritic cells are central, and tamoxifen has a blocking effect
      on dendritic cells. METHODS: We present 5 cases of estrogen dermatitis in which
      the clinical features were prurigo, urticaria, acneiform eruption and annular
      erythema. RESULTS: Tamoxifen was effective in 3 of 4 cases. Three of 4 biopsy
      specimens showed the formation of Langerhans cell nests in the epidermis and hair
      follicles and perivascular infiltration of CD4+ and CD8+ lymphocytes in the
      dermis. CONCLUSION: These results suggest that a dendritic-cell-mediated allergic
      mechanism is involved in estrogen dermatitis.

PMID- 14571069
TI  - Improvement of mild inflammatory changes of the facial skin induced by winter
      environment with daily applications of a moisturizing cream. A half-side test of
      biophysical skin parameters, cytokine expression pattern and the formation of
      cornified envelope.
AB  - OBJECTIVE: Based on our previous findings that, reflecting mild inflammation, the
      exposed facial skin shows much poorer functional properties of the stratum
      corneum (SC) in the dry and cold winter than those evaluated in the same
      individuals in the warm and humid summer time, we conducted a half-side test on
      the face to determine how the facial skin changes induced by a winter environment
      are improved by daily applications of a moisturizing cream as assessed by non
      invasive biophysical and cytological methods. METHODS: One side of the face of 16
      young females was treated with a moisturizing cream twice daily for 6 weeks, with
      the other side serving as the non-treated control. Before treatment, 3 and 6
      weeks after the start of the treatment, high-frequency conductance as a parameter
      of the skin surface hydration, transepidermal water loss (TEWL), a parameter of
      the water barrier function of the skin, and the skin surface lipid level were
      measured on the cheeks. Obtaining the SC from the skin surface by adhesive tape,
      interleukin (IL) 1alpha and IL-1 receptor antagonist (IL-1ra) in the SC and
      cornified envelope (CE) maturation were determined. RESULTS: At first, baseline
      measurements conducted before treatment showed rather high TEWL values suggestive
      of an impaired skin barrier. During the treatment with the moisturizing cream,
      significantly higher conductance values and lower TEWL values were found on the
      moisturizer-treated side, accompanied by a decreasing IL-1ra/IL-1alpha ratio and
      immature CEs. CONCLUSION: These results suggested that the daily application of a
      moisturizing cream is effective in improving mild subclinical inflammation that
      is induced on the facial skin by the winter environment.

PMID- 14571070
TI  - Jessner's lymphocytic infiltration of the skin: a CD8+ polyclonal reactive skin
      condition.
AB  - BACKGROUND: Jessner's lymphocytic infiltration of the skin (JLIS) is a clinically
      and histologically distinct disease entity. Conflicting results have been
      reported concerning its differentiation from cutaneous lupus erythematosus and
      polymorphous light eruption, its relationship to palpable migratory arciform
      erythema and its classification as a B-cell or a CD4+ T-cell lymphoproliferative
      disease. OBJECTIVE: Our study was performed in order to re-evaluate JLIS
      clinically and by immunohistochemical and molecular analyses. METHODS: Stringent
      inclusion/exclusion criteria were used to collect a cohort of 34 patients with
      JLIS that did not overlap with lupus erythematosus or polymorphous light
      eruption. Clinical data were analysed, and immunohistochemical and molecular
      studies were performed including TCR-gamma PCR GeneScan software analysis of
      tissue and peripheral blood samples. RESULTS: In the majority of the patients,
      the lesions consisted only of papules and plaques while in 12% annular lesions
      were also seen. The lesions were found on the face (38%), on the trunk and arms
      (50%) or at both sites (12%). Immunohistochemical analyses revealed a clear
      predominance of T cells in all patients, and of CD8+ T cells in 77% of the
      patients. As judged by TCR-gamma PCR GeneScan analysis, 98 and 79% of the tissue
      and peripheral blood samples, respectively, showed a polyclonal T-cell
      population; identical T-cell clones were not detected concomitantly in both the
      skin and the peripheral blood of the same patient. CONCLUSIONS: JLIS occurs at 2
      major predilection sites, that is the face and trunk. Therefore introduction of
      palpable migratory arciform erythema as a separate entity is not justified. The
      lymphoid infiltrates are dominated immunohistochemically by CD8+ T cells that do
      not show clonality on molecular analysis. Thus, JLIS represents a characteristic
      CD8+ polyclonal reactive skin condition.

PMID- 14571071
TI  - Poikilodermatous subacute cutaneous lupus erythematosus.
AB  - BACKGROUND: Subacute cutaneous lupus erythematosus (SCLE) is a distinct subset of
      lupus erythematosus with unique clinical, immunological and genetic features.
      Among the unusual variants of SCLE, there is a poikilodermic presentation.
      However, to date, only 1 case of poikilodermatous SCLE has been reported.
      OBJECTIVE: Our goal was to summarize the clinical characteristics and course as
      well as the pathological, laboratory and immunofluorescence findings of 4
      patients with poikilodermatous SCLE. METHODS: A retrospective study was conducted
      including 54 patients diagnosed as having SCLE between 1980 and 2002. RESULTS:
      Four patients (7.4%) had SCLE. All patients were alive, and none developed severe
      systemic involvement in up to 36 years (median, 24 years) after the onset of
      disease. The most noteworthy laboratory finding was the cutaneous deposition of
      amyloid. CONCLUSION: Poikilodermatous SCLE represents an uncommon variant within
      the clinicopathological spectrum of SCLE following a favorable course, in spite
      of extensive cutaneous involvement. Photosensitivity is the pathomechanism
      explaining, theoretically, the development of both poikiloderma and cutaneous
      amyloidosis in such cases.

PMID- 14571072
TI  - Improving sun protection behaviour in children: study design and baseline results
      of a randomized trial in Italian elementary schools. The 'Sole Si Sole No GISED'
      project.
AB  - OBJECTIVE: To evaluate, in the context of a randomized study, the 'Sole Si Sole
      No GISED' project, the effectiveness of an educational intervention to improve
      sun protection behaviour in schoolchildren. METHODS: A large number of primary
      schools (classes II and III) in Italy were randomized to an educational
      intervention or control group: The intervention was conducted by trained teachers
      using ad hoc developed materials. Attitudes toward sun exposure and behaviour
      while in the sun were assessed at baseline and 1 year after concluding the
      educational intervention. In a subgroup of children, melanocytic naevi were
      counted on the upper limbs at the same intervals. The pilot phase of the study
      was started in 2001. RESULTS: During the pilot phase, a total of 4,233 children
      was recruited. Of these, 2,116 were randomized to the active intervention and
      2,117 to the control group. No difference for any of the study variables was
      documented between the 2 groups at baseline. About 20% of the children reported
      intense sun exposure during the year preceding the study. About 88% of the
      children reported adequate modalities of sun protection. Sunscreens were commonly
      used. A total of 508 children (12%) reported a history of sunburns in the year
      preceding the start of the study. Melanocytic naevi were counted in a total of
      1,503 children (852 in the experimental and 651 in the control group). No
      differences in terms of skin, hair and eye colours were documented between the
      experimental and the control groups. The mean naevus count at baseline was 9.6
      (median 7) in the experimental group and 10.1 (median 8) in the control group.
      CONCLUSION: About 50% of the total expected number of children was recruited
      during the pilot phase of the study. Randomization proved to be an excellent
      modality to select 2 samples similar for all the important study variables
      examined. A history of sunburns was reported less frequently than expected. The
      'Sole Si Sole No GISED programme' is one of the few examples of a controlled
      evaluation of the effectiveness of an educational intervention in Italy.

PMID- 14571073
TI  - Evaluation of medium-dose UVA1 phototherapy in localized scleroderma with the
      cutometer and fast Fourier transform method.
AB  - PURPOSE: To evaluate the efficacy of medium-dose UVA1 phototherapy in patients
      with localized scleroderma. METHOD: A controlled pilot study with medium-dose
      UVA1 (48 J/cm2) was performed. The results were evaluated by means of a skin
      score and two objective methods for quantifying sclerosis (cutometer and fast
      Fourier transform method). Patients were treated 4 times a week for 5 weeks. The
      follow-up period was 12 weeks. RESULTS: All patients responded to therapy. Skin
      score and cutometer results showed improvement of skin elasticity of treated skin
      compared to control skin. Fast Fourier transform measurements showed no change in
      bundle orientation ratio and spacing. CONCLUSION: We concluded that treatment for
      12 weeks 4 times a week with medium-dose UVA1 may be a beneficial therapy and a
      well-tolerated treatment modality for localized scleroderma (morphea). After 12
      weeks, improvement of skin sclerosis can be detected by skin score and cutometer
      measurements but not by the fast Fourier transform method.

PMID- 14571074
TI  - Complementary medicine and psoriasis: linking the patient's outlook with evidence
      based medicine.
AB  - BACKGROUND: There is increasing evidence for the extensive use of complementary
      and alternative medicine (CAM) by patients with psoriasis. Clinical research in
      the arena of CAM and psoriasis treatment is evolving and includes some randomized
      controlled trials. OBJECTIVE: To study CAM use among patients with psoriasis
      attending a dermatology clinic in a major university hospital in northern Israel.
      Prevalence, reasons for CAM use and its relevance to doctor-patient communication
      were emphasized. METHODS: Semistructured interviews were conducted with psoriasis
      patients in a dermatology clinic. Consent was obtained for 78 patients. Post
      visit questionnaires were given to 5 physicians. RESULTS: Seventy-eight patients
      with psoriasis were interviewed and 77 were studied. Sixty-two percent used CAM.
      Fifty-eight percent of users had seen a CAM practitioner. The study found a trend
      of CAM use among patients with psoriasis from Arab compared to Jewish descent
      (p=0.087). CAM users reported on average 2 different CAM modalities. Herbal
      medicine and nutritional treatments ranked first, followed by homeopathy,
      traditional Chinese medicine and nutritional supplements. The main reason for CAM
      use was stated to be to do everything to heal the disease, followed by a quest
      for improved quality of life. Others mentioned an interest in a less toxic
      treatment, disappointment with conventional treatment and stress reduction. Well
      over half of the study participants and their dermatologists did not initiate a
      discussion about CAM use. The dermatologists' ability to predict CAM use in their
      patients was relatively low. CONCLUSION: There is growing evidence of extensive
      CAM use among patients with psoriasis. Most patients use CAM as a complementary
      treatment, rather than an alternative to conventional treatment. Teaching CAM
      should be integrated into the dermatology residency curriculum. Dermatologists
      need to increase their awareness of CAM use by their patients in order to improve
      therapeutic communication.

PMID- 14571075
TI  - Male-pattern baldness is common in men with X-linked recessive ichthyosis.
AB  - BACKGROUND: X-linked recessive ichthyosis (XRI) is a relatively common genetic
      disorder of keratinization caused by deficiency in steroid sulfatase (STS)
      activity. STS appears to play an important role in testosterone metabolism.
      Therefore it has been discussed that the presence of normally functioning STS may
      be a presupposition for the development of androgenetic alopecia (AGA). METHODS:
      Patients with the diagnosis of XRI were sent questionnaires. RESULTS AND
      CONCLUSIONS: We reviewed 26 cases with XRI and noticed 11 patients with AGA in an
      advanced stage. The existence of two pathways for the steroid biosynthesis may be
      the explanation for a compensatory mechanism in XRI males. The Delta5 pathway
      depends on steroid sulfate activity, whereas the working Delta4 pathway produces
      AGA in XRI males.

PMID- 14571076
TI  - Predominant telangiectatic erythema in linear atrophoderma of Moulin: novel
      variant or separate entity?
AB  - Linear atrophoderma of Moulin is a distinctive disease originally described in
      1992 and characterized by acquired, mildly atrophic, non-sclerotic, slightly
      hyperpigmented lesions following the lines of Blaschko. Here, we describe a 15
      year-old girl with a 13-year history and a 29-year-old male with a 6-year history
      of prominent linear telangiectatic erythema and mild atrophoderma following the
      lines of Blaschko that involved the right leg and hip, and both legs, the trunk
      and both arms, respectively. As pronounced telangiectatic erythema within lesions
      of atrophoderma of Moulin has not hitherto been described, we propose that the
      disease in our patients represents a novel variant of linear atrophoderma of
      Moulin. Due to considerable overlap, we do not favour the notion that our cases
      constitute an entity entirely separate from linear atrophoderma of Moulin.

PMID- 14571077
TI  - Secondary anetoderma overlying pilomatrixomas.
AB  - Five pilomatrixomas with anetodermic cutaneous changes are presented. Four large
      tumors revealed soft, atrophic, pink translucent skin covering a firm
      subcutaneous mass, and their appearance was similar to that of a keloid or
      hypertrophic scar. One small tumor revealed soft, slightly atrophic, reddened or
      purplish skin covering a firm subcutaneous mass: its clinical appearance was
      similar to that of a hematoma or minor infection. Histopathological examination
      of the skin showed atrophic and edematous changes in the dermis associated with
      diminished fragmented collagen and absent elastic tissue. It is supposed that the
      dermal atrophic appearance bears a relation to the loss of elastic fibers and the
      dermal edema is related to the leakage of lymphatic fluid. Both phenomena may be
      caused by continuous pressure from the outside, as these anetodermic
      pilomatrixomas were located where they were apt to be exposed to mechanical
      irritation.

PMID- 14571078
TI  - Multiple eruptive dermatofibromas with CD34+ cells in a patient with
      hypertriglyceridemia.
AB  - Multiple eruptive dermatofibromas (MEDF) are rare and have been thought to be
      associated with altered immunity. It has been reported that dermatofibromas (DFs)
      are positive for factor X IIIa but not for CD34. In this report, we describe a 34
      year-old Japanese woman with MEDF and persistent hypertriglyceridemia.
      Histopathological examination revealed that several areas in larger nodules,
      showing higher cellularity and storiform growth pattern, had CD34+ cells. Our
      case and the review of previous reports suggest that hyperlipidemia, including
      hypertriglyceridemia, could induce MEDF and that highly cellular areas in DFs are
      sometimes positive for CD34.

PMID- 14571079
TI  - Repigmentation of vitiligo with pimecrolimus cream: a case report.

PMID- 14571080
TI  - Development of multiple paronychia and periungual granulation in patients treated
      with gefitinib, an inhibitor of epidermal growth factor receptor.

PMID- 14571081
TI  - Topical treatment of lentigo maligna melanoma with imiquimod 5% cream.

PMID- 14571082
TI  - Imatinib (STI-571)-induced exfoliative dermatitis in a Saudi patient with deck
      chair sign.

PMID- 14571083
TI  - Pigmented purpuric dermatitis preceding the diagnosis of mycosis fungoides by 24
      years.

PMID- 14571084
TI  - Mycophenolate mofetil in epidermolysis bullosa acquisita.

PMID- 14571085
TI  - Mast cells in atopic dermatitis: resistance against medium-dose UVA1
      phototherapy?

PMID- 14571086
TI  - Coexistence of psoriasis and pemphigus after enalapril intake.

PMID- 14571087
TI  - Two cases of cephalic Becker nevus with asymmetrical growth of beard or scalp
      hair.

PMID- 14571088
TI  - Acute diffuse and total alopecia of the female scalp: a new subtype of diffuse
      alopecia areata that has a favorable prognosis--a reply.

PMID- 14571090
TI  - Erosion and ulceration occurring on oral lichen planus. Comments on the article
      'Erosive lichen planus: what is this?' by A. Rebora.

PMID- 14571091
TI  - Methoxypsoralen-induced sleep disorder.

PMID- 14571092
TI  - Malnutrition--the ignored risk factor.

PMID- 14571094
TI  - Nutritional support in acute pancreatitis.
AB  - Acute pancreatitis (AP), mainly the severe necrotizing type, results in extreme
      energy demands which might lead, if prolonged, to severe malnutrition. Besides
      that, starving during AP contributes to gut barrier dysfunction, the main cause
      of bacterial translocation and sepsis. The aim of nutritional support in AP is to
      prevent malnutrition and protect the gut by maintaining mucosal integrity.
      Traditionally, nutritional support during the acute phase of the disease has been
      provided through total parenteral nutrition (TPN) solutions. However, recent
      animal and human studies have identified new patterns of pancreatic secretion and
      hormonal stimulation during the course of AP, different from those assumed for
      years. Thus it has become feasible to use the natural enteral route for nutrition
      with potential benefits compared with TPN.

PMID- 14571093
TI  - What we have learned about cachexia in gastrointestinal cancer.
AB  - It is appreciated widely by clinicians that significant malnutrition accompanies
      malignant processes in approximately 50% of patients and eventually leads to
      severe wasting which accounts for approximately 30% of cancer-related deaths
      overall, 30-50% of deaths in patients with gastrointestinal tract cancers, and up
      to 80% of deaths in patients with advanced pancreatic cancer. The body wasting
      known as cancer cachexia is a complex syndrome characterized by progressive
      tissue depletion and decreased nutrient intake that is manifested clinically as
      inexplicable, recalcitrant anorexia and inexorable host weight loss. Decreased
      nutritional intake, increased metabolic expenditure and dysfunctional metabolic
      processes, including hormonal and cytokine-related abnormalities, all appear to
      play roles in the development of cancer cachexia. Although this condition of
      advanced protein-calorie malnutrition, sometimes described as the cancer anorexia
      cachexia syndrome, is not entirely understood, it appears to be multifactorial,
      is a major cause of morbidity and mortality in cancer patients, and ultimately
      leads to death. Therapeutic interventions have met with little success, and,
      regardless of tremendous efforts throughout the decades, the exact nature of the
      mediators responsible for cancer cachexia remain elusive. The pathogenesis of
      cancer cachexia appears to be related to proinflammatory cytokines, alterations
      in the neuroendocrine axis and tumor-derived catabolic factors. Despite trials of
      conventional and/or aggressive nutritional support by a myriad of feeding
      techniques, patients with cancer cachexia have failed to gain consistent
      significant benefits in terms of weight gain, functional ability, quality of life
      or survival. Additionally, attempts to ameliorate the abnormal clinical and
      metabolic features of cancer cachexia with a variety of pharmacologic agents have
      met with only limited success. Either until cancer of the gastrointestinal tract
      can be cured or until it is possible to identify the exact causes and mechanisms
      of the cancer cachexia syndrome, the most realistic and practical options
      currently are directed toward minimizing adverse gastrointestinal side effects or
      complications of the malignant process and/or therapy, as well as increasing
      appetite, food intake and nutrient utilization in an effort to enhance quality of
      life and improve survival.

PMID- 14571095
TI  - Nutrition and inflammatory bowel disease: its relation to pathophysiology,
      outcome and therapy.
AB  - Nutritional deficiencies are frequent in patients with ulcerative colitis and
      Crohn's disease, and negatively influence the outcome of the disease. Growth
      retardation, osteopenia and thromboembolic phenomena are some of the inflammatory
      bowel disease complications in which nutritional deficits are involved. Moreover,
      nutrients can play a role in the pathogenesis of the disease and, in some cases,
      can be a primary therapeutic tool. Enteral nutrition has proven to play a
      therapeutic role in Crohn's disease. The nutrient(s) responsible for this effect
      are not well identified but dietary fat appears to be a major factor. In
      ulcerative colitis, unabsorbable carbohydrates can modulate the intestinal
      microbial environment, thus contributing to improve colonic inflammation.

PMID- 14571096
TI  - Factors enhancing intestinal adaptation after bowel compensation.
AB  - Intestinal failure (IF) refers to the condition in which certain causes lead to
      derangements in nutrient absorption capacity. Gut adaptation occurs in response
      to IF and it is both morphologic and physiologic in nature and can be mediated by
      growth factors and nutrients. Our paper reviews certain trophic growth factors
      that have important interactions relevant for intestinal growth, function and
      adaptation. DATA SOURCE: The literature was reviewed (data from both animal and
      human studies) and certain trophic factors that modulate intestinal adaptation
      are summarized. The factors reviewed are: epidermal growth factor, insulin-like
      growth factor I and II, transforming growth factor alpha and beta, neurotensin,
      interleukin-11, glucagon-like peptide-2, keratinocyte growth factor, human growth
      hormone, short-chain fatty acids, and glutamine. CONCLUSIONS: Growth factors
      augment intestinal proliferation, diminish programmed apoptosis, and modulate the
      adaptive process. They also have the potential to improve nutrient absorption in
      some bowel disease. The enhancement of gut adaptation may allow patients to
      transition of parenteral/enteral to normal nutrition, in a shorter period of
      time, which reduce the rate of adverse effects caused by artificial nutrition and
      improve quality of life.

PMID- 14571097
TI  - Helicobacter pylori infection, vitamin B12 and homocysteine. A review.
AB  - It has been suggested that there is an association between Helicobacter pylori
      infection, reduced cobalamin absorption and cobalamin status and, consequently,
      elevated homocysteine levels. This would offer an explanation why H. pylori
      infection is associated with coronary heart disease. To date, more than 25
      studies have been published that either deal with H. pylori infection and
      homocysteine, H. pylori infection and cobalamin status, or both. The design of
      these studies differs widely in terms of definition of H. pylori status,
      measuring cobalamin status, selection of study cohorts and geographical study
      areas. Therefore, results are fairly inconclusive at present and do not suggest a
      major role of H. pylori infection in the development of cobalamin deficiency and
      elevated homocysteine levels.

PMID- 14571098
TI  - Prevalence of malnutrition in hospitalized medical patients: impact of underlying
      disease.
AB  - BACKGROUND/AIMS: Malnutrition is common among hospitalized patients. We
      investigated whether certain diseases predispose more frequently for malnutrition
      than others. METHODS: Nutritional state was assessed by clinical scores,
      anthropometry and bioimpedance analysis in 502 consecutively admitted patients in
      the departments of internal medicine in two hospitals in Berlin (n = 300,
      university hospital; n = 202, district hospital). The prevalence of malnutrition
      was compared in patient groups with a different diagnosis. RESULTS: Malnutrition
      was present in 24.2% of all patients. A clear association between diagnoses and
      malnutrition was found: the prevalence of malnutrition was significantly higher
      in malignant than in non-malignant diseases (50.9 vs. 21.0%, p < 0.0001). High
      prevalence rates >30% were observed in subgroups of patients with inflammatory
      bowel diseases, chronic heart failure and benign lung diseases. Patients with
      gastrointestinal diseases, however, were not more frequently malnourished than
      other medical patients (28.8 vs. 22.0%). Malnourished patients were significantly
      older (70.0 +/- 13.6 vs. 58.3 +/- 15.6 years, p < 0.0001) and had a 40% longer
      hospital stay (13.1 +/- 8.1 vs. 9.3 +/- 6.8 days, p < 0.0001) than well-nourished
      patients. CONCLUSIONS: Patients with malignancies, inflammatory bowel disease,
      chronic heart failure and benign lung diseases need special attention due to the
      high prevalence of malnutrition.

PMID- 14571099
TI  - Sugar intake, taste changes and dental health in Crohn's disease.
AB  - BACKGROUND: An increased intake of sucrose has been reported in patients with
      Crohn's disease (CD). Since subclinical zinc deficiency reduces taste perception
      for sweet, we investigated taste perception, sucrose intake and plasma zinc
      levels as well as dental status in CD patients. METHODS: Carbohydrate intake and
      plasma zinc levels were assessed in 24 CD patients and 24 age-matched controls
      (Con). Taste threshold for sucrose, oral hygiene and caries prevalence were
      evaluated. RESULTS: In CD a higher sucrose intake (CD 107.1 +/- 27.7 vs. Con 71.9
      +/- 13.7 g/day; p < 0.001), a higher taste threshold for sweet (CD 7.31 vs. Con
      2.91 g/l; p < 0.001) and lower plasma zinc levels (CD 11.5 +/- 1.5 vs. Con 13.5
      +/- 2.0 micromol/l; p < 0.001) were found. API was poor (CD 85.4 +/- 23.6, Con
      31.8 +/- 24.1, p < 0.001) and correlated with sucrose intake (p < 0.01). Caries
      prevalence was increased in patients with longer disease (>3 years) (DMFT index:
      >3 years 15.6 +/- 5.7 vs. <3 years 9.5 +/- 4.3; p < 0.05). CONCLUSION: Dental
      status in CD patients is poor. Both increased sugar consumption and insufficient
      oral hygiene seem to cause the higher caries prevalence. Obviously, patients with
      CD belong to a high-risk group, and preventive measures should be taken early in
      the course of the disease.

PMID- 14571100
TI  - Serum mineral levels in children with intestinal parasitic infection.
AB  - Parasitic infections are highly prevalent in the general population. A relation
      between a parasitic infection and absorption of minerals is not an easy task.
      Serum levels of copper, zinc and magnesium were prospectively measured in 64
      children with intestinal parasitic infection. Thirty-nine children with
      Enterobius vermicularis were treated with pyrantel pamoate and 25 children with
      Giardia lamblia with tinidazole and metronidazole. Three months after treatment,
      significant differences in serum copper, zinc and magnesium were seen in patients
      with E. vermicularis infection, and in serum magnesium levels in patients with G.
      lamblia. Although the pathogenic mechanism is not clear, these findings could
      reflect a deficiency related to malabsorption due to mucous affection. Early
      detection and treatment of intestinal parasitosis could avoid these serum mineral
      deficiencies.

PMID- 14571101
TI  - Impact of body mass index on fasting blood glucose concentration among
      Helicobater pylori carriers.
AB  - BACKGROUND/AIMS: Despite the fact that Helicobacter pylori (Hp) is regarded as a
      major gastroduodenal pathogen, it has recently been suggested to be an important
      factor for non-gastroenterologic conditions such as diabetes mellitus.
      Accordingly, it seems that Hp infection may have implications in glycemic control
      and in fasting plasma glucose concentrations. As overnutrition and obesity are
      directly related to impaired glucose tolerance, the aim of the present study was
      to determine whether Hp infection leads to alterations in fasting plasma glucose
      concentrations of Hp carriers and especially in relation to their body mass
      index. METHODS: Serum was obtained from 224 young, male navy recruits. An enzyme
      linked immunosorbent assay to detect Hp-specific IgG serum antibodies as well as
      gastroscopy along with biopsy was used to identify the infected individuals.
      Serum levels of glucose, urea, creatinine and uric acid were also determined. Non
      fasting subjects and persons with abnormal oral glucose tolerance curve test were
      excluded. RESULTS: Among Hp-positive individuals, obese persons presented with a
      significantly lower mean blood glucose level than non-obese persons. Obese Hp
      contaminated participants had significantly lower mean fasting blood glucose
      concentrations as well as a significantly smaller percentage of participants with
      abnormal elevated blood glucose levels than obese participants negative to Hp
      infection. CONCLUSIONS: Our data suggest that obesity in combination with Hp
      infection may induce an enhanced response to insulin leading to reduced fasting
      blood glucose levels, among Hp-positive obese persons in comparison to Hp
      positive lean persons.

PMID- 14571102
TI  - Selenium is depleted in Crohn's disease on enteral nutrition.
AB  - BACKGROUND/AIMS: [corrected] Selenium is an important trace element and its
      deficiency has been reported to be associated with cardiomyopathy or
      gastrointestinal cancer. The aim of this study is to clarify the selenium status
      in Crohn's disease (CD) on enteral nutrition. METHODS: We measured serum selenium
      concentrations in 53 patients with CD and compared them with those in 21 healthy
      controls. Twenty-nine patients were under the treatment by enteral nutrition (EN
      group), and the remaining 24 patients were free from formulated enteral nutrition
      (non-EN group). RESULTS: While the serum selenium concentration in the non-EN
      group was not decreased when compared to controls, the value in the EN group was
      significantly lower than those in the non-EN group and in controls. Clinical
      manifestations of selenium deficiency were found in a patient on exclusive
      enteral nutrition. In the EN group, the serum selenium concentration showed an
      inverse correlation with the duration and the daily dose of enteral nutrition. In
      the non-EN group, the serum selenium concentrations were inversely correlated
      with the Crohn's disease activity index. CONCLUSION: These findings suggest that
      patients with CD on enteral nutrition are at risk for selenium deficiency and
      that even patients without enteral nutrition may develop selenium deficiency at
      the active phase of the disease.

PMID- 14571103
TI  - L-Carnitine in the treatment of mild or moderate hepatic encephalopathy.
AB  - Hepatic encephalopathy (HE) is one of the major complications of cirrhosis.
      Experimental and clinical findings observed in liver, muscle and brain have
      provided new insights into the ammonia mechanism of action. L-Carnitine (LC),
      inducing ureagenesis, may decrease blood and brain ammonia levels. 120 patients
      meeting inclusion criteria were randomized either to a treatment for 60 days with
      LC or placebo (2 g twice a day). Previous studies have reported a significant
      protective effect of LC in mice and rats, which is associated with a significant
      reduction of blood and brain ammonia concentration, suggesting an action of LC
      either at peripheral or central sites. Results of our study show a protective
      effect of LC in ammonia-precipitated encephalopathy in cirrhotic patients. Either
      in subjects with HE 1 or 2 we observed a significant reduction at day 30 and more
      markedly at day 60 of treatment. A significant therapeutic effect of LC was also
      observed in the NCT-A, which is an accepted and reliable psychometric test for
      the assessment of mental function in cirrhotic patients with HE.

PMID- 14571104
TI  - Fructose breath hydrogen test--is it really a harmless diagnostic procedure?
AB  - Usage of hydrogen breath tests has become one of the standard procedures in
      diagnosing chronic unspecific abdominal pain. These tests are said to be of
      sufficient specificity and sensitivity, are easily done, non-invasive and are
      more often practiced in outpatients. A 13-year-old boy is reported with chronic
      unspecific abdominal pain and growth retardation and so far misdiagnosed
      hereditary fructose intolerance (HFI), who developed life-threatening adverse
      effects during the fructose breath hydrogen test. It is concluded that the
      possibility of HFI should be excluded first by a carefully explored dietary
      history before the fructose breath test is performed under medical supervision.
      If there is any suspicion of HFI, a molecular genetic analysis should be
      preferred.

PMID- 14571106
TI  - Inflammatory bowel diseases 2003--from genetics to biological therapy.

PMID- 14571105
TI  - Screening for iron overload in the Turkish population.
AB  - BACKGROUND/AIMS: Hereditary hemochromatosis (HH), the most common autosomal
      recessive disease in the white population, is characterized by excessive
      gastrointestinal absorption of iron and loading of parenchymal organs. HFE
      mutations of C282Y and H63D are largely responsible for HH in populations of
      Celtic ancestry. Although many screening studies related to HH have been done in
      Northern Europe, the USA and Australia, as yet, no such study has been published
      on Turkey. In this study we aimed to screen the Turkish population for iron
      overload. METHODS: Random samples were obtained from 4,633 healthy adults (3,827
      male, 806 female, mean age +/- SD 35 +/- 8 years, range 14-76) for the
      measurement of transferrin saturation (TS). Measurements were repeated after an
      overnight fast in the subjects whose initial TS was > or =50%. Serum ferritin
      levels and C282Y and H63D gene mutations were studied in cases when fasting TS
      was > or =50%. In cases where the serum ferritin level was >200 ng/ml with or
      without HFE mutations, liver biopsy was performed for histological evaluation and
      determination of iron content. RESULTS: In 158 subjects, TS was > or =50% in the
      non-fasting state. A second determination of TS after an overnight fast was
      performed in 135 subjects. In 26 subjects, the TS was > or =50% in the fasting
      state. HFE mutation and serum ferritin levels were measured in these 26 subjects.
      Eleven subject (10 male, 1 female) were heterozygote and 1 male subject was
      homozygote in reference to H63D. C282Y mutation was not found. Four of these 26
      subjects (all males, aged 23, 24, 40, 49) had increased serum ferritin levels and
      liver biopsy was performed. In 1 male (aged 49) who was heterozygote for H63D
      genotype with a serum ferritin level of 645 ng/ml, iron overload in liver tissue
      was shown by histology as well as atomic absorption spectrophotometry.
      CONCLUSION: The prevalence of hemochromatosis in the Turkish population is much
      lower in comparison to populations of Celtic ancestry and C282Y mutation is non
      existent.

PMID- 14571107
TI  - Genetics of inflammatory bowel diseases--past, present, and future.
AB  - In this review, the evidence to support the multifactorial and polygenic nature
      of the disease is briefly described. The past of genetics of inflammatory bowel
      disease (IBD) is characterized by unfulfilled promises and is now closed with a
      new vision and a new promise coming from a genetic epidemiology approach. The
      genome-wide screening has led to the first gene of IBD and has given a new
      insight into the regulation of chronic inflammation. The future of IBD will be
      under scrutiny of the visionaries, but also the skeptics and the enthusiasts.

PMID- 14571108
TI  - Environmental influences on inflammatory bowel disease manifestations. Lessons
      from epidemiology.
AB  - Environmental factors play an important role in the disease manifestation, course
      and prognosis of inflammatory bowel disease. Observations on temporal trends and
      geographical distribution point at risk factors associated with a Western
      lifestyle. A large number of studies have been performed on various factors such
      as diet, smoking, and several infectious agents. Childhood exposures modifying
      immune responses in later life form a particularly interesting field. However, so
      far, only smoking in Crohn's disease, and smoking cessation in ulcerative colitis
      can be considered established as risk factors for the manifestation of the
      disease. Smoking is also associated with a poor prognosis in Crohn's disease. A
      strong negative association of appendectomy with ulcerative colitis has been very
      consistent across many studies; however, the implications of this finding are
      still obscure.

PMID- 14571109
TI  - Rationale for probiotic and antibiotic treatment strategies in inflammatory bowel
      diseases.
AB  - Inflammatory bowel diseases (IBD), commonly referred to as Crohn's disease and
      ulcerative colitis are chronic aggressive disorders which share many similarities
      concerning pathomechanism and clinical course, but have very distinct features.
      Both entities are mainly located in areas with high bacterial concentrations,
      such as the terminal ileum and cecum in Crohn's disease and the rectum in
      ulcerative colitis. In recent years, overwhelming evidence accumulated,
      supporting the hypothesis that IBD are characterized by a genetically determined,
      overly aggressive immune response towards ubiquitous luminal antigens, especially
      commensal bacteria and their products. Trials in both human IBD and experimental
      colitis have demonstrated that broad-spectrum antibiotics may influence the
      course of ulcerative colitis and Crohn's disease and antibiotics with narrow
      activity against the anaerobic fraction of the flora can prevent relapse in
      Crohn's disease after surgically induced remission. Since relevant antibiotic
      strategies can be associated with some side effects, the ongoing research
      recently focused on alternative methods to modify the intestinal flora in
      patients with IBD. Clinical observations including few controlled trials, basic
      research, and animal studies have suggested a potential role for probiotic
      bacteria within the treatment regimens for IBD. However, the mode of action of
      these organisms is still largely unclear and in vitro studies are inconclusive.
      This review summarizes recent in vitro and in vivo data regarding the role of the
      intestinal microflora in the pathogenesis of chronic intestinal inflammation and
      possible therapeutic mechanisms of probiotic bacteria relevant to IBD.
      Furthermore, we will review clinical trials examining the efficacy of antibiotic
      and probiotic treatment strategies in IBD.

PMID- 14571110
TI  - New diagnostic avenues in inflammatory bowel diseases. Capsule endoscopy,
      magnetic resonance imaging and virtual enteroscopy.
AB  - The modalities for diagnostic imaging in patients with inflammatory bowel disease
      (IBD) have dramatically changed in the last decade. Several years ago the only
      methods to assess the small bowel were conventional enteroclysis or a small bowel
      'follow through'. Nowadays, wireless capsule endoscopy as well as magnetic
      resonance imaging (MRI) with virtual endoscopy represent new evolving methods to
      depict and assess the small bowel. This article describes these recently
      introduced methods in the diagnostic assessment of the small bowel and discusses
      the clinical significance based on the current literature.

PMID- 14571111
TI  - Osteoporosis and other extraintestinal symptoms and complications of inflammatory
      bowel diseases.

PMID- 14571112
TI  - Standard therapy of Crohn's disease.
AB  - Therapy of Crohn's disease is either counteracting the underlying mechanisms of
      bowel inflammation or specifically targeting certain complications of disease,
      e.g. strictures, fistulae, bacterial overgrowth, or anemia. The therapeutic
      arsenal is well defined and has been tested for safety and efficacy. There is
      need and opportunity to adapt therapies to individual situations. This is made on
      the basis of scientific facts that have been collected from randomized controlled
      trials and on the basis of reasoned thinking that weighs the potential effect
      against potential side effects in individual cases. In clinical practice, the
      potency of lifestyle changes such as smoking cessation is still underestimated
      and not extensively exploited. As the understanding of genetic mutations, their
      gene function and phenotypic expression grows, we anticipate that future
      treatment can be tailored to certain genotypes or phenotypes of Crohn's disease.

PMID- 14571113
TI  - Standard treatment of ulcerative colitis.
AB  - Ulcerative colitis (UC) is an idiopathic, chronic inflammation of the colon which
      may present with a range of mild to severe symptoms. The disease may be localized
      to the rectum or can be more extensive and involve the left side of the colon or
      the whole colon. Treatment in UC is directed towards inducing and maintaining
      remission of symptoms and mucosal inflammation. The key parameters to be assessed
      for the most appropriate treatment are the severity and extent of the
      inflammation. Meta-analyses of published trials have shown that topical treatment
      with 5-aminosalicylic acid (5-ASA) is the treatment of choice in active distal
      mild-to-moderate UC. Oral aminosalicylates are effective in both distal and
      extensive mild-to-moderate disease, but in distal disease, the rates of remission
      are lower than those obtained with topical 5-ASA. New steroids, such as
      budesonide and beclomethasone dipropionate (BDP), administered as enemas,
      constitute an alternative to 5-ASA therapy. In some studies, these have been
      shown to be as effective as conventional steroids but with significantly lower
      inhibition of plasma cortisol levels. Patients with unresponsive disease or those
      with more severe presentation will require oral corticosteroids and sometimes
      intravenous therapy. Approximately 10% of patients with unresponsive UC have
      severe attacks requiring hospitalization. Patients with severe disease should be
      managed jointly by a medical and surgical team, and intensive intravenous
      treatment should be started with high-dose steroids. Early recognition of failure
      of therapy will allow the introduction of immunosuppressive therapy with
      intravenous cyclosporine. Patients who respond are shifted to oral cyclosporine
      associated with azathioprine/6-mercaptopurine, whereas those who fail will
      require proctocolectomy. Oral aminosalicylates are the first-line therapy in
      maintenance of remission. Topical 5-ASA may play a role in distal disease.
      Patients who are steroid dependent can be started on azathioprine or 6
      mercaptopurine although it may take up to 3 months for the treatment to become
      effective. They may have reversible immediate side effects, such as pancreatitis
      or bone marrow suppression, which disappear upon discontinuation of therapy.
      Close monitoring of these hematologic and biochemical parameters will improve
      safety. The use of biologic therapy with infliximab in more severe disease has
      not been established.

PMID- 14571114
TI  - Surgery for inflammatory bowel diseases.
AB  - Surgery is required in many patients with inflammatory bowel disease at some
      point in their disease. In patients with ulcerative colitis, surgery is
      potentially curative whereas recurrence of Crohn's disease following surgery is a
      common occurrence. As a result, the indications and surgical management of the
      two diseases may be quite different. Surgery is usually reserved for the
      management of complications or failure of medical treatment in Crohn's disease.
      Resection of the diseased segment is the usual procedure performed. While surgery
      usually results in an improvement in quality of life, recurrence of disease
      occurs frequently with reported rates of 5-90% at 1 year, depending on the
      criteria used. To date, there have been no surgical maneuvers which have been
      shown to decrease the risk of recurrence. Over the past few decades, several
      advances have been made in the surgical management of Crohn's disease: use of
      strictureplasty for extensive disease; use of laparoscopic techniques to perform
      surgery and the performance of the ileal pouch procedure in very selected
      patients. Significant advances in the surgical management of ulcerative colitis
      have been made in the past 50 years. Although there are several options available
      to patients, the preferred option now is the ileal pouch procedure. With
      technical modifications and with experience, this procedure can now be performed
      with a low complication rate, with good functional results and quality of life
      and excellent long-term outcome.

PMID- 14571115
TI  - Biological therapy in IBD. Anti-tumor necrosis factor-alpha and others.
AB  - Currently used standard treatment in IBD is effective and sufficient for the
      majority of patients. Published numbers regarding therapy refractoriness are
      probably related to referral centers and not representative. Pharmacological
      optimization of available drugs improves the standard situation further.
      Biological therapies in a larger meaning are studied intensively, but obviously
      hopes are to some extent not real. Biological and for some principles clinical
      effects (i.e. TNF antibodies, CD4 antibodies) are proven, the effects are,
      however, limited and long-term risks and results are not clarified. Numerous
      approaches are not clinically relevantly effective which is, in particular, true
      for those inhibiting single mediators. A number of alternative concepts such as
      hormones and growth factors could be effective and will be studied further. In
      particular probiotics may be a development of the future and they belong to the
      'biologic treatments' in the true sense.

PMID- 14571116
TI  - The acid-tolerant microbiota associated with plaque from initial caries and
      healthy tooth surfaces.
AB  - The intent of this study was to compare the inherent acid tolerance of bacteria
      in samples of dental plaque from tooth sites in subjects with and without initial
      caries. Plaque was collected from approximal surfaces showing early enamel caries
      and from healthy tooth surfaces in the same subjects, as well as from enamel
      surfaces of caries-free individuals. In addition to plating on blood agar, the
      plaque samples were plated directly on non-selective solid agar medium buffered
      to pH 7.0, 6.0, 5.5, 5.0, 4.5 and 4.0 to avoid any loss of adaptation to acid
      during primary isolation of plaque bacteria. The results showed that
      approximately 50% of the total cultivable plaque microbiota from caries, as well
      as healthy tooth sites, was able to grow at pH 5.5 and 1% at pH 5.0, pH values
      regarded as critical for the demineralization of tooth enamel. At pH 5.0, members
      of the genus Streptococcus were the dominant group, but mutans streptococci
      accounted for less than half of the streptococcal viable count. The other acid
      tolerant streptococcal isolates included Streptococcus anginosus, Streptococcus
      constellatus, Streptococcus gordinii, Streptococcus intermedius, Streptococcus
      mitis, Streptococcus oralis, Streptococcus salivarius and SStreptococcus sanguis.
      Analysis of the results indicated that the mutans streptococci in dental plaque
      were highly variable with respect to acid tolerance, and that both caries and
      healthy sites harboured significant numbers of mutans streptococci that were not
      acid-tolerant.

PMID- 14571117
TI  - Xylitol inhibition of acid production and growth of mutans Streptococci in the
      presence of various dietary sugars under strictly anaerobic conditions.
AB  - The aim of this study was to investigate the inhibitory effect of xylitol on the
      growth of and acid production by mutans streptococci in the presence of various
      dietary sugars, and the relationship between the inhibition and the accumulation
      of xylitol 5-phosphate (X5P) under strictly anaerobic conditions like those in
      the deep layers of dental plaque. Xylitol retarded the growth of mutans
      streptococci in the presence of glucose (G), galactose (Gal), maltose (M),
      lactose (L) or sucrose (S) as an energy source, though the inhibition of growth
      on fructose (Fr) was small. Xylitol inhibited acid production by washed cells of
      Streptococci mutans from G, Gal, M, L or S (12-83% inhibition). S. mutans
      accumulated X5P intracellularly through activity of the phosphoenolpyruvate
      xylitol phosphotransferase system (PEP-xylitol PTS) when they fermented these
      sugars in the presence of xylitol. However, in the presence of Fr, no inhibition
      of acid production was observed. In addition, the amounts of X5P during the
      fermentation of Fr were smaller than those of other sugars in spite of the
      presence of PEP-xylitol PTS activity. These results suggest that along with the
      intracellular accumulation of X5P, xylitol decreases the growth and acid
      production of mutans streptococci in the presence of various dietary sugars
      except Fr.

PMID- 14571119
TI  - Ion release from copper phosphate cement and influence on Streptococcus mutans
      growth in vitro: a comparative study.
AB  - The aim of this study was to compare the effects of a black copper cement (BCC),
      an established restorative material (a conventional glass ionomer cement) and two
      temporary restorative materials (a zinc phosphate and a zinc polycarboxylate
      cement) on the growth of Streptococcus mutans in vitro, and to correlate
      bacterial growth with ion release from each material. Test specimens were eluted
      in either 0.1 M lactic acid, pH 4, or 0.1 M sodium chloride, pH 7. At 2 days, 7
      days, 28 days and 6 months, eluates were inoculated with S. mutans and bacterial
      growth was recorded. Metal ion (Cu(2+), Zn(2+ )and Mg(2+)) and fluoride release
      were measured. At most immersion times, the different materials had a
      statistically significant inhibitory effect on bacterial growth compared to the
      respective control, at both pH levels. The inhibitory effect decreased with time
      and in most cases was associated with high levels of ion release at the beginning
      of the experimental period, followed by significantly lower levels. For BCC,
      there were statistically significant relationships between the median rates of
      growth of S. mutans in the presence of BCC eluates and the median values for
      release of copper and zinc, although not magnesium. Of the different materials,
      BCC demonstrated greatest antibacterial activity.

PMID- 14571118
TI  - Fermentation of five sucrose isomers by human dental plaque bacteria.
AB  - Sucrose has five structural isomers: palatinose, trehalulose, turanose, maltulose
      and leucrose. Although these isomers have been reported to be noncariogenic
      disaccharides, which cannot be utilized by mutans streptococci, there is no
      information about their fermentability by other bacteria in dental plaque. The
      purpose of the present study was to examine whether these isomers were fermented
      by predominant bacteria in human dental plaque. Clinical bacterial isolates
      obtained from dental plaque from 3 children aged 22 months to 50 months (146
      strains) were inoculated into 3 ml of peptone-yeast extract (PY medium)
      containing glucose for 1 day, then an aliquot of 20 microl of culture medium was
      inoculated into 1 ml of PY medium containing 1% (w/v) of the respective test
      carbohydrates. After incubation for 1 day, the pH values and the optical density
      at 660 nm of the cultures were measured. Fermentation ability was measured by pH
      <or=5.5, growth by an OD(660) of >or=0.5. Of the clinical isolates, 33% fermented
      palatinose, and 69% of these were Actinomyces species. All of the palatinose
      fermenting bacterial strains fermented trehalulose, 25% fermented turanose, 70%
      fermented maltulose and 23% fermented leucrose. We therefore conclude that, in
      human dental plaque, there are significant numbers of bacteria that are able to
      ferment sucrose isomers.

PMID- 14571120
TI  - Synergistic inhibitory effect of cationic peptides and antimicrobial agents on
      the growth of oral streptococci.
AB  - Although chlorhexidine is one of the most efficacious antimicrobial agents used
      for the prevention of dental caries, side effects limit its application. The
      effects of gaegurin 6 (GGN6), an animal-derived cationic peptide, and its
      derivatives PTP6 and PTP12 on the growth of oral streptococci were investigated
      to assess the potential of these agents for use in the prevention of dental
      caries. The minimal inhibitory concentrations of the peptides for inhibition of
      the growth of oral streptococci (Streptococcus mutans , S. sobrinus, S. sanguis
      and S. gordonii) ranged from 1.2 to 8.2 muM. The peptides also exhibited marked
      synergistic antibacterial effects with chlorhexidine or xylitol. The most
      effective combinations (fractional inhibitory concentration index of 0.5) were
      xylitol with GGN6 against S. gordonii 10558 and chlorhexidine with either GGN6 or
      PTP6 against S. sobrinus OMZ-175. These results indicate that cationic peptides
      alone or in combination with chlorhexidine or xylitol might prove effective for
      the inhibition of the growth of cariogenic oral streptococci in situ.

PMID- 14571122
TI  - In vivo effectiveness of laser fluorescence compared to visual inspection and
      radiography for the detection of occlusal caries in primary teeth.
AB  - The purpose of this study was to evaluate the in vivo effectiveness of laser
      fluorescence compared to visual inspection and radiography for the detection of
      occlusal caries in primary teeth. Fifty sites from 30 molars in 29 patients were
      selected and evaluated under standardized conditions by 2 previously trained
      examiners according to the 3 diagnostic methods. Histological examination served
      as gold standard after exfoliation or extraction. Values obtained for
      sensitivity, specificity and accuracy were 0.60, 0.90 and 0.73 for laser
      fluorescence, 0.82, 0.85 and 0.84 for visual inspection and 0.62, 0.73 and 0.67
      for radiography, respectively. Considering only dentinal caries, values were
      0.73, 0.95 and 0.90 for laser fluorescence, 0.61, 1.00 and 0.90 for visual
      inspection and 0.96, 0.81 and 0.85 for radiography, respectively. We conclude
      that for the detection of occlusal caries in primary molars laser fluorescence
      presents a similar accuracy when compared to visual inspection and radiography,
      although visual inspection showed better values for sensitivities for both enamel
      and dentin lesions.

PMID- 14571121
TI  - Influence of oral detergents and chlorhexidine on soft-layer electrokinetic
      parameters of the acquired enamel pellicle.
AB  - Electron microscopy has described the salivary pellicle as an 'uneven, knotted
      structure'. This study describes a novel soft-layer model of salivary pellicles,
      based on measured electrophoretic mobilities and the influence of dentifrices and
      a chlorhexidine mouthwash on the parameters of the model. The enamel surface was
      found to possess a high number of fixed, negative charges (zN = -62 mM) and to be
      electrophoretically hard (1/lambda = 0.6 nm), i.e. impenetrable to fluid flow.
      Adsorption of a salivary pellicle resulted in a fourfold reduction in the surface
      fixed charge density (zN = -15 mM) along with an increase in electrophoretic
      softness (1/lambda = 2.3 nm). Exposure of pellicles to various dentifrices
      containing sodium fluoride as an active component and sodium lauryl sulfate as a
      detergent had little effect on the surface fixed charge densities (varying
      between -15 and -30 mM, depending on the dentifrice involved) and electrophoretic
      softnesses (varying between 2.3 and 3.4 nm). Exposure of pellicles to a
      dentifrice containing sodium fluoride and hexametaphosphate as an additional
      detergent yielded soft (8.0 nm) pellicles, penetrable to fluid flow, with few
      fixed, negative charges (1 mM). This is opposite to the effects of chlorhexidine,
      which created an electrophoretically hard pellicle (1.7 nm). This soft-layer
      electrokinetic model quantitatively shows that the degree to which pellicles are
      penetrable to fluid flow differs upon exposure to dentifrices, with relevance for
      plaque formation, de- and remineralization and staining processes.

PMID- 14571123
TI  - Evaluation of the effectiveness of laser fluorescence in monitoring in vitro
      remineralization of incipient caries lesions in primary teeth.
AB  - The purpose of this investigation was to examine the effectiveness of laser
      fluorescence for monitoring in vitro remineralization of caries lesions.
      Seventeen natural enamel lesions in primary molars were each cut into two parts.
      One part was exposed, at room temperature, to a remineralizing solution
      (experimental) and the other part to water (control) for 28 days. Laser
      fluorescence readings were taken at the beginning of the experiment and during
      the experiment. At the end of the experiment, lesion depth in the experimental
      halves was significantly less than in the control halves (p < 0.01), suggesting
      that remineralization had occurred. However, the laser fluorescence readings
      showed no statistically significant changes during the experiment, either in the
      experimental or control halves. We conclude that laser fluorescence was not able
      to detect in vitro remineralization of natural incipient caries lesions of
      primary teeth.

PMID- 14571124
TI  - In vitro study of remineralization of dentin: effects of ions on mineral
      induction by decalcified dentin matrix.
AB  - We examined the effects of various ions on the mineralization of dentin matrix in
      vitro. Demineralized dentin matrix was incubated in a metastable calcium
      phosphate solution with or without silicate, fluoride, calcium, phosphate,
      magnesium or silver. Insoluble dentin matrix induced mineral formation after
      incubation for 10.2 h in the metastable solution without added ions. Silicate at
      5 microM and fluoride at 40 microM significantly reduced the mineral induction
      time. At least 200 microM calcium or 100 microM phosphate was required to promote
      mineral induction. Conversely, magnesium and silver concentrations as low as 10
      and 2 microM inhibited mineral induction. The mineral induced by each sample
      after incubation for 24 h was identified by its X-ray diffraction pattern as
      apatite. We concluded that silicate is a stronger inducer of remineralization of
      dentin matrix than fluoride, calcium or phosphate, and that magnesium and silver
      inhibit the induction of remineralization of dentin matrix.

PMID- 14571125
TI  - Comparative study of wear of enamel induced by alternating and simultaneous
      combinations of abrasion and erosion in vitro.
AB  - Two types of interaction of erosive and abrasive forces with human enamel were
      analysed in an in vitro study. To simulate toothbrushing or chewing after an
      acidic challenge, enamel specimens were eroded in 0.3% citric acid (pH 3.2), then
      brushed with or without silica abrasive. To simulate simultaneous erosion and
      abrasion, as would occur during chewing of abrasive acidic food, enamel specimens
      were abraded in a toothbrushing machine, with and without silica abrasive, while
      immersed in citric acid. Enamel wear was measured by profilometry. In both
      experiments the combination of erosion and abrasion resulted in significantly
      greater wear than erosion alone, but no significant differences in wear after
      brushing with or without abrasive were found. Simultaneous erosion and abrasion
      resulted in about 50% more wear than alternating erosion and abrasion. It is
      concluded that softened enamel is highly unstable and potentially easily removed
      by short and relatively gentle physical action. Chewing of acidic foods with some
      abrasive properties might cause enhanced tooth wear.

PMID- 14571126
TI  - Relationship between the presence of demarcated opacities and hypoplasia in
      permanent teeth and caries in their primary predecessors.
AB  - OBJECTIVE: To investigate the relationship between the presence of demarcated
      opacities and hypoplasia on permanent teeth and the caries status of the primary
      predecessor teeth in a cohort of Chinese children. METHODS: The study sample
      consisted of 250 children living in a non-fluoridated area in Southern China
      whose caries status of primary teeth at the age of 3-6 years had been recorded
      annually in a previous study. A follow-up examination of their permanent teeth
      was conducted when they were about 12 years old. The presence of enamel defects
      was determined by consensus of 2 dentists according to the modified DDE index.
      RESULTS: 56.8% of the 250 children examined had demarcated opacities, while 10.8%
      of them had hypoplasia. Demarcated opacities and hypoplasia were found in 5.8 and
      1.3% of the teeth examined, respectively. A higher prevalence of demarcated
      opacities was found in those permanent teeth of which their primary predecessor
      teeth had caries than in those without (7.5 vs. 3.8%, p < 0.001). A similar
      finding was obtained for the prevalence of hypoplasia (1.9 vs. 0.4%, p < 0.001).
      CONCLUSION: There was an association between caries in primary teeth and the
      presence of demarcated opacities and hypoplasia in their permanent successors.

PMID- 14571128
TI  - Learning to karyotype in the university environment: a computer-based virtual
      laboratory class (KaryoLab) designed to rationalize time for the tutor/researcher
      and to encourage more students to engage in cytogenetics.
AB  - The ability to karyotype G-banded chromosome preparations is an essential skill
      for chromosome biologists. For this reason, the teaching of the rudiments of G
      banding analysis forms an integral part of the curriculum in many biology and
      genetics degree courses. The way in which karyotyping is usually taught involves
      providing the students with a photograph of G-banded chromosomes, a pair of
      scissors and some glue from which they can cut out the chromosomes and build the
      karyotype. This has the disadvantage that large amounts of time are taken in
      cutting and pasting and comparatively little in learning pattern recognition of
      individual chromosomes. In this paper we describe the development of a computer
      based student practical class "KaryoLab". To the best of our knowledge, this is
      the first report of a teaching tool that combines instruction in cytogenetic
      analysis with both formative and summative feedback to the student and a virtual
      elimination of marking time for the tutor. Chromosome research and diagnostics
      will only continue while there are sufficiently motivated and trained individuals
      to perform it. We see the software developed here as a significant step towards
      training and motivating students in cytogenetics.

PMID- 14571127
TI  - Ten-year incidence of tooth loss and dental caries in elderly Swedish
      individuals.
AB  - There has been a significant reduction in edentulism and the elderly retain more
      teeth into old age. The 10-year incidence of tooth loss, coronal and root caries
      was studied in a random sample of inhabitants of Goteborg, who were 55, 65 and 75
      years old at baseline. Of the 208 persons examined at baseline, 102 (49%)
      participated in the follow-up examination: 56, 37 and 9, respectively, in the
      different age groups of 65, 75 and 85 years. In addition, for the purpose of time
      trend comparisons, a new random sample of 98 individuals aged 55 years was
      examined. The mean numbers of remaining teeth were 24, 23, 17 and 14,
      respectively, in the age groups of 55, 65, 75 and 85. The corresponding mean
      numbers at baseline were 23, 19 and 17, respectively, in those subjects who were
      then 55, 65 and 75 years old. Forty-eight percent had lost no teeth during the 10
      year period, while 13% had lost more than 2 teeth. The major reason for tooth
      extraction was dental caries and it was found in 60% of all cases. The incidence
      of coronal caries decreased, while that of root caries increased with age (p <
      0.01). Comparing the same age groups, the frequency of root caries had decreased
      during the 10-year period. It could be concluded from this study that elderly
      people were determined to retain their teeth for as long as possible, but dental
      caries may be a problem among the very old.

PMID- 14571129
TI  - Parental origin of the two additional haploid sets of chromosomes in an embryo
      with tetraploidy.
AB  - We report on the molecular investigations performed on an embryo with
      tetraploidy, karyotype 92,XXXY. The embryo was spontaneously aborted after eight
      weeks of gestation. Molecular analyses were performed in order to determine the
      parental origin and mode of formation of the two additional haploid sets of
      chromosomes. Microsatellite markers mapping to pericentromeric chromosome regions
      were used. Our results show a maternal origin of one additional set of
      chromosomes most likely due to the incorporation of the polar body of meiosis I
      and a paternal origin of the second additional set of chromosomes most likely due
      to dispermy. The karyotype 92,XXXY is rather unusual, indeed the vast majority of
      cases with tetraploidy have the karyotypes 92,XXXX or 92,XXYY. To the best of our
      knowledge this is the first case with 92,XXXY for which molecular investigations
      have been performed.

PMID- 14571130
TI  - How common are common fragile sites in humans: interindividual variation in the
      distribution of aphidicolin-induced fragile sites.
AB  - To obtain an estimate of the variation in common fragile sites (CFSs) among
      individuals, aphidicolin (APC)-induced chromosomal breakage data were analyzed
      for 20 karyotypically normal adult humans. As it is specifically designed to meet
      the analytical requirements for considering fragile sites as presence/absence
      characters in single individuals, the FSM methodology (Bohm et al., 1995) was
      used to statistically distinguish fragile from nonfragile sites. These analyses
      indicated that the APC-induced fragile sites are not ubiquitous but vary
      extensively among individuals; the per-individual number of fragile sites ranged
      from as few as seven to as many as 20. Of the 45 different sites identified as
      fragile, 19 (42%) occurred in more than half of the individuals, but only two
      sites (3p14 and 16q23) were fragile in all of the individuals; 12 (27% of the
      total) were fragile in single individuals only. Although these analyses provide
      statistical confirmation (and initial estimates of population variation) for 43
      of the 88 APC-inducible fragile sites currently recognized as occurring among
      humans, they are consistent with the hypothesis that many of the currently
      recognized human CFSs have been erroneously identified. These results indicate
      the need for per-individual statistical identification of CFSs for larger samples
      of individuals and that studies of particular fragile sites should be conducted
      on individuals documented to be fragile at the loci under consideration.

PMID- 14571131
TI  - Cloning and characterization of the human neural cell adhesion molecule, CNTN4
      (alias BIG-2).
AB  - We report the isolation and characterization of human contactin 4 (CNTN4), a
      brain-derived, immunoglobulin superfamily molecule-2 (alias BIG-2) as a candidate
      gene responsible for the differentiation potential of human neuroblastoma cells.
      Northern blot analysis showed highest CNTN4 expression in testes, thyroid, small
      intestine, uterus and brain. Induction of CNTN4 mRNA expression in human
      neuroblastoma tumor cells treated with retinoic acid correlated with a block in
      retinoid-induced neuritogenesis. Our findings suggest a role for human contactin
      4 protein in the response of neuroblastoma cells to differentiating agents.

PMID- 14571132
TI  - Heterochromatin polymorphism associated with 18S rDNA: a differential pathway
      among Hoplias malabaricus fish populations.
AB  - The distribution of constitutive heterochromatin has showed a relevant
      association with karyotypic evolution in several animal groups. In the present
      paper, a polymorphic condition for a heterochromatic segment overlapping a
      nucleolar organizer region in the fish species Hoplias malabaricus from the
      Iguacu river, Southern Brazil, was analyzed. In accordance with previous studies,
      this population belongs to cytotype A, showing 2n = 42 meta-submetacentric
      chromosomes, without differentiation of sex chromosomes. Three phenotypes were
      established with regard to the heterochromatin located near the centromere of
      chromosome pair 16, and named rr for homomorphic reduced bands, dd for
      homomorphic duplicated bands and rd for the heteromorphic condition. The rr
      phenotype was predominant (70.6%), followed by rd (23.5%) and dd (5.9%), showing
      Hardy-Weinberg equilibrium in the population. In addition, the 18S rDNA sites
      also show the polymorphic condition. A possible role for this NOR/heterochromatin
      segment in the evolution of sex chromosomes in other H. malabaricus cytotypes is
      discussed.

PMID- 14571133
TI  - The chromosomal complement of the artedidraconid fish Histiodraco velifer
      (Perciformes: Notothenioidei) from Terra Nova Bay, Ross Sea.
AB  - The karyotype of Histiodraco velifer from the Antartic Ocean was analyzed using
      various banding methods and in situ hybridization with a telomeric probe. A male
      and a female had a diploid set of 46 chromosomes (6 submetacentric + 40
      acrocentric, FN = 52); the nucleolar organizer was CMA3-positive and was located
      on the short arm of a medium-sized submetacentric pair. All chromosomes stained
      uniformly with DAPI, whereas C-banding revealed heterochromatic blocks that were
      mostly located centromerically and telomerically and were resistant to ALUI
      digestion. The substantial identity of the karyotype of H. velifer with that of
      the other artedidraconids investigated so far suggests that chromosome changes
      must have played a less than significant role in the speciation among the
      lineages of this fish family endemic to Antarctica.

PMID- 14571134
TI  - Molecular characterization of the canine HMGB1.
AB  - Due to the close similarities of numerous canine diseases to their human
      counterparts, the dog could join the mouse as the species of choice to unravel
      the genetic background of complex diseases as e.g. cancer and metabolic diseases.
      Accordingly, the role of the dog as a model for therapeutic approaches is
      strongly increasing. However, prerequisite for such studies is the
      characterization of the corresponding canine genes. Recently, the human high
      mobility group protein B1 (HMGB1) has attracted considerable interest of
      oncologists because of what is called its "double life". Besides its function as
      an architectural transcription factor HMGB1 can also be secreted by certain cells
      and then acts as a ligand for the receptor for advanced glycation end products
      (RAGE). The binding of HMGB1 to RAGE can activate key cell signaling pathways,
      such as p38(MAPK), JNK, and p42/p44(MAPK) emphasizing the important role of HMGB1
      in inflammation and tumor metastasis. These results make HMGB1 a very interesting
      target for therapeutic studies done in model organisms like the dog. In this
      study we characterized the molecular structure of the canine HMGB1 gene on
      genomic and cDNA levels, its predicted protein, the gene locus and a basic
      expression pattern.

PMID- 14571135
TI  - Clarifications on breakpoints in HSAX and BTAX by comparative mapping of F9,
      HPRT, and XIST in cattle.
AB  - The coagulation factor IX gene (F9), the hypoxanthine phosphoribosyl transferase
      1 gene (HPRT1), and the X-inactive specific transcript gene (XIST) were
      physically assigned in cattle to analyze chromosomal breakpoints on BTAX recently
      identified by radiation hybrid (RH) mapping experiments. Whereas the FISH
      assignment of XIST indicates a similar location on the q-arm of the human and
      cattle X chromosomes, the locus of HPRT1 supported the assumption of a chromosome
      rearrangement between the distal half of the q-arm of HSAX and the p-arm of BTAX
      identified by RH mapping. F9 previously located on the q-arm of BTAX was assigned
      to the p-arm of BTAX using RH mapping and FISH. The suggested new position of F9
      close to HPRT1 supports the homology between HSAXq and BTAXp. The F9 locus
      corresponds with the gene order found in the homologous human chromosome segment.
      XIST was assigned on BTAXq23, HPRT1 and F9 were mapped to BTAXp22, and the
      verification of the location of F9 in a 5000 rad cattle-hamster whole genome
      radiation hybrid panel linked the gene to markers URB10 and HPRT1.

PMID- 14571136
TI  - Cytogenetics of the razor clam Solen marginatus (Mollusca: Bivalvia: Solenidae).
AB  - The razor clam Solen marginatus has a diploid chromosome number of 38. The
      karyotype consists of one metacentric/submetacentric, three
      submetacentric/metacentric, five submetacentric, one
      submetacentric/subtelocentric, one subtelocentric/submetacentric, six
      subtelocentric and two telocentric chromosome pairs. Staining with chromomycin A3
      revealed bright positive bands subcentromerically in the long arms of one medium
      sized subtelocentric pair, while DAPI staining showed uniform fluorescence in all
      chromosomes of the complement. Fluorescence in situ hybridization using an 18S
      5.8S-28S rDNA probe locates these loci at the subcentromeric region of one
      subtelocentric pair and at the subtelomeric region of another subtelocentric
      pair.

PMID- 14571137
TI  - Cloning and genomic organization of the TTL gene on mouse chromosome 2 and human
      chromosome 2q13.
AB  - Tubulin tyrosine ligase (TTL) is a cytosolic enzyme involved in the
      posttranslational modification of tubulin. In the assembled form microtubules are
      detyrosinated over time at the C-terminus of alpha-tubulin. After microtubular
      disassembly TTL restores tyrosine residues back to the detyrosinated tubulin
      leading to a cycle of detyrosination/tyrosination. Here we report the isolation
      of the human and mouse TTL cDNA. In comparison with other known TTL sequences,
      namely bovine, rat and porcine, we found that only porcine TTL deviates in length
      by having an insertion of two glutamate residues. In mouse and human TTL the
      genomic coding sequence is composed of seven exons with normal intron/exon
      boundaries. Using fluorescence in situ hybridization (FISH), we mapped the murine
      TTL gene to mouse chromosome 2 (MMU2). Human TTL has been located to chromosome
      2q13 (HSA2q13). In addition, we found frequently truncated PCR products of hTTL
      transcripts with aberrant splicing in tumors.

PMID- 14571138
TI  - Chromosome banding in Amphibia. XXVII. DNA replication banding patterns in three
      anuran species with greatly differing genome sizes.
AB  - The mitotic chromosomes of three anuran species, Scaphiopus holbrooki, Litoria
      infrafrenata and Odontophrynus americanus, were analyzed by means of the 5
      bromodeoxyuridine/deoxythymidine (BrdU/dT) replication banding technique. These
      species exhibit large differences in their genome sizes: S. holbrooki possesses
      one of the smallest genomes among vertebrates, L. infrafrenata has a genome size
      near the modal DNA value of most Amphibia, whereas O. americanus is a tetraploid
      species. BrdU/dT labeling induces reproducible and reliable R- and G-replication
      bands along the metaphase chromosomes of all three species. Irrespective of the
      genome size of the species considered, the number of early (R-) and late (G-)
      replicating bands per haploid karyotype is nearly the same. The chromosomes of
      the autotetraploid O. americanus can be arranged into sets of four homologous
      chromosomes (quartets). C-bands and BrdU/dT replication bands reveal
      heterogeneity within the quartets 1, 3 and 4 that are interpreted as the
      initiation of a diploidization process.

PMID- 14571139
TI  - Chromosome banding in Amphibia. XXVIII. Homomorphic XY sex chromosomes and a
      derived Y-autosome translocation in Eleutherodactylus riveroi (Anura,
      Leptodactylidae).
AB  - Extensive cytogenetic analyses on a population of the leptodactylid frog
      Eleutherodactylus riveroi in northern Venezuela revealed the existence of
      multiple XXAA male/XYAA female/XAA(Y) female sex chromosomes. The XAA(Y)
      karyotype originated by a centric (Robertsonian) fusion between the original,
      free Y chromosome and an autosome. 46.2% of the male individuals in this
      population are carriers of this Y-autosome fusion. In male meiosis the XAA(Y) sex
      chromosomes pair in the expected trivalent configuration. In the same population
      53.8% of the male animals still possess the original, free XY sex chromosomes. E.
      riveroi is only the second vertebrate species discovered in which a derived Y
      autosome fusion coexists with the ancestral free XY sex chromosomes. The free XY
      sex chromosomes, as well as the multiple XA(Y) sex chromosomes are still in a
      very primitive (homomorphic) stage of differentiation. With no banding technique
      applied it is possible to distinguish the Y from the X. Various banding
      techniques and in situ hybridizations have been carried out to characterize the
      karyotypes. DNA flow cytometric measurements show that the genome size of E.
      riveroi resembles that of other Eleutherodactylus species. The cytogenetic data
      obtained in E. riveroi are compared with those of the sole other vertebrate known
      to possess the extremely rare, multiple XXAA male/XYAA female/XAA(Y) female sex
      chromosomes. Surprisingly enough, this vertebrate again is a frog belonging to
      the genus Eleutherodactylus [E. ((maussi) biporcatus] which lives exactly in the
      same habitat in northern Venezuela as does E. riveroi.

PMID- 14571140
TI  - Chromosome banding in Amphibia. XXIX. The primitive XY/XX sex chromosomes of Hyla
      femoralis (Anura, Hylidae).
AB  - The karyotype of the pine woods treefrog, Hyla femoralis, is characterized by
      primitive XY female/XX male sex chromosomes. The sole difference between the X
      and the Y is the presence of a nucleolus organizer region (NOR) in the X. Due to
      a deletion of the NOR in the Y, this chromosome is distinctly smaller than the X.
      Since no autosomal NORs exist in the karyotype of this species, the NOR deletion
      in the Y results in a sex-specific difference in the number of ribosomal RNA
      genes, with a female:male ratio of about 2:1. Interphase nuclei of male animals
      contain always one silver-stained nucleolus, whereas most nuclei of female
      specimens exhibit two nucleoli. This is in agreement with the absence of dosage
      compensation for sex-linked genes in amphibian cells. The consequences of the
      loss of about 50% of ribosomal RNA genes for the viability of male individuals
      and spermatogenesis are discussed.

PMID- 14571141
TI  - Replication banding and FISH analysis reveal the origin of the Hyla femoralis
      karyotype and XY/XX sex chromosomes.
AB  - The pine woods treefrog, Hyla femoralis, is unique among North American hylid
      frogs in having a metacentric chromosome 6 and heteromorphic sex chromosomes of
      the XY/XX type. The X chromosome is distinguished by having a nucleolar
      organizing region (NOR) in the short arm. The Y chromosome does not possess an
      NOR. Until the present study, it was not known if the NOR was not present on the
      Y chromosome or inactive and therefore not detectable by conventional cytogenetic
      methods like silver staining. Exclusive of its unique features the karyotype of
      H. femoralis closely resembles those of North American frogs with karyotypes like
      H. chrysoscelis. We used replication banding and fluorescence in situ
      hybridization (FISH) with a DNA probe to the 18S + 28S ribosomal genes, which are
      located at the NOR, to characterize the H. femoralis karyotype. Our analysis
      revealed that the 18S + 28S ribosomal genes are not present on the Y chromosome,
      and that the karyotype of H. femoralis was derived from an H. chrysoscelis-like
      karyotype by relocation of the NOR to the X chromosome from chromosome 6 and
      either a concurrent or subsequent pericentric inversion of chromosome 6.

PMID- 14571142
TI  - Elucidation of correspondence between swine chromosome 4 and human chromosome 1
      by assigning 27 genes to the ImpRH map, and development of microsatellites in the
      proximity of 14 genes.
AB  - Loci affecting swine intramuscular fat content, backfat thickness, carcass
      weight, and daily weight gain were assigned to regions of swine chromosome (SSC)
      4, which were shown to correspond to human chromosome (HSA) 1p22--> q25 by ZOO
      FISH, bidirectional chromosome painting, as well as by the linkage map of genes.
      In order to select candidate genes responsible for the above traits from the
      human genome database, precise correspondence between SSC4 and HSA1 is a
      prerequisite. In the present study, 27 genes, PTGFR, GBP1, GBP2, GFI1, GCLM,
      ABCD3, EXTL2, KCNA3, ADORA3, KCND3, WNT2B, NRAS, SYCP1, PTGFRN, IGSF2, NOTCH2,
      S100A10, SHC1, SSR2, LMNA, CCT3, CD5L, PEA15, FCER1G, EAT2, DDR2, and LAMB3,
      located in the HSA1 region corresponding to SSC4 or possibly SSC4, were assigned
      to the IMpRH map. The alignment of genes from centromere to telomere in the SSC4
      q arm is basically conserved in HSA1p22-->q25 with the direction from the q arm
      to the p arm, which is in good agreement with results from linkage mapping. In
      addition, the present study first demonstrated that WNT2B residing in the middle
      of the HSA1 region was assigned to SSC18 with a high lod score (> 5), and that at
      least three intrachromosomal rearrangements occurred in the region in the process
      of swine and human evolution. PTGFR, and LAMB3 localized at both ends of the HSA1
      region were assigned to SSC6 and SSC9, respectively, which is consistent with
      regional correspondence reported earlier. In the course of the above analysis,
      microsatellite markers were developed in the proximity of eleven genes localized
      on SSC4, and three genes on other swine chromosomes.

PMID- 14571143
TI  - ROC curves are a suitable and flexible tool for the analysis of gene expression
      profiles.

PMID- 14571144
TI  - Assignment of monoglyceride lipase (MGLL) gene to bovine chromosome 22q24 by in
      situ hybridization and confirmation by radiation hybrid mapping.

PMID- 14571145
TI  - Assignment of lymphocyte antigen 64 homolog, radioprotective 105 kDa (LY64) gene
      to porcine chromosome band 16q14 with somatic cell hybrids and linkage mapping.

PMID- 14571146
TI  - Assignment of the canine myosin Va gene (MYO5A) to chromosome 30q14 by
      fluorescence in situ hybridization and radiation hybrid mapping.

PMID- 14571147
TI  - Assignment of the porcine janus kinase 1 gene (JAK1) to chromosome 6q34-->q35 by
      fluorescence in situ hybridization and radiation hybrid mapping.

PMID- 14571148
TI  - Assignment of the RAB27A gene to canine chromosome 30q15.1 by fluorescence in
      situ hybridization and radiation hybrid mapping.

PMID- 14571149
TI  - Assignment of the methylmalonyl-CoA mutase gene (MUT) to porcine chromosome 7q13-
      >q14 by in situ hybridization and analysis of radiation hybrid panels.

PMID- 14571150
TI  - Selective serotonin reuptake inhibitor augmentation in the treatment of negative
      symptoms of schizophrenia.
AB  - The treatment of negative symptoms of schizophrenia presents a major clinical
      challenge. This review examines the evidence pertaining to the efficacy,
      tolerability and safety of adding selective serotonin reuptake inhibitors (SSRIs)
      to antipsychotic agents in the treatment of negative symptoms in schizophrenia.
      Important methodological issues such as differentiating primary and secondary
      negative symptoms are discussed. The balance of available evidence indicates that
      at least some SSRIs, fluvoxamine and fluoxetine, can ameliorate primary negative
      symptoms in chronic schizophrenia patients who are treated with typical
      antipsychotics. The combination is safe and well tolerated although, as
      antipsychotic drug concentrations may be elevated, attention to dose and drug
      monitoring should be considered as appropriate. The effect of SSRI augmentation
      of atypical antipsychotics requires further study. Combination with clozapine may
      require particular caution because of potential toxicity if serum clozapine
      levels rise steeply. SSRI augmentation may be a useful addition to the treatment
      of schizophrenia.

PMID- 14571152
TI  - Reducing the dose of antipsychotic medications for those who had been treated
      with high-dose antipsychotic polypharmacy: an open study of dose reduction for
      chronic schizophrenia.
AB  - Antipsychotic medications are often used at higher than the recommended dose and
      sometimes in a combination regimen to treat schizophrenia. However, in general,
      high-dose therapies have been abandoned in recent clinical studies. In this
      study, dose reduction of antipsychotic medication was implemented for patients
      with chronic schizophrenia, most of whom (81%) had been treated with an
      antipsychotic high-dose polypharmacy regimen consisting of more than 1000 mg/day
      in total amount. The results show that merely reducing the amount of
      antipsychotic led to favourable outcome in 23 out of 41 cases (56%), with another
      13 cases (32%) showing no change. Dose reduction ended in failure in only five
      subjects (12%). Overall, the amount as well as the number of antipsychotic
      medications was significantly reduced from 1984 mg to 812 mg per day (reductions
      of 59% and from 3.6 to 2.2, respectively; both P<0.0001). The Global Assessment
      of Functioning scale improved from 30.6 to 37.2, which reached significance
      (P<0.001). Accordingly, the Severity of Illness improved from 4.7 to 4.2, and was
      also significant (P<0.01). Dose reduction is an encouraging strategy to consider
      for those patients with schizophrenia who have chronically been treated with high
      dose antipsychotic polypharmacy, even if judged unavoidable in the past.

PMID- 14571151
TI  - A score for predicting response to pharmacotherapy in obsessive-compulsive
      disorder.
AB  - Although there have been many attempts to find predictors of therapeutic response
      to antidepressant treatment of obsessive-compulsive disorder (OCD), few reports
      have evaluated the joint predictive value of a number of clinical
      characteristics. This study aimed to identify clinical predictors of outcome in
      OCD, and to develop an easily applicable method to predict response to drug
      treatment. One hundred and fifty patients with primary OCD according to DSM-IV
      criteria were randomly assigned in a 12-week, double-blind, comparison trial with
      a selective serotonin reuptake inhibitor (paroxetine), and a serotonin
      noradrenaline reuptake inhibitor (venlafaxine). The primary efficacy parameter
      was the Yale-Brown obsessive-compulsive scale (Y-BOCS) score, and response to
      treatment was prospectively defined as a >/= 35% decrease from the beginning. A
      stepwise multivariate analysis was used to identify predictors. The absence of
      previous therapies, moderate baseline severity of obsessive-compulsive symptoms
      (Y-BOCS score < 23), and low Hamilton Depressive Rating Scale scores (6-15) were
      found to be prognostic determinants of good response to pharmacotherapy. The
      prognostic ability of the prediction model to discriminate between responders and
      non-responders was quantified as the area under the receiver operating/operator
      characteristic curve (ROC area), which was 0.71 (95% confidence interval 0.63
      0.8), demonstrating a reasonable discriminatory power. This study is the first to
      present a model that can estimate by the use of prediction rules the probability
      of treatment response to antidepressants in patients with OCD.

PMID- 14571153
TI  - Incidence and determinants of antidepressant drug use in migraine patients.
AB  - The purpose of this retrospective, follow-up study was to characterise the use of
      antidepressant medication in a defined migraine population and evaluate the
      determinants thereof. Data was obtained from the PHARMO-RLS prescription
      database. Our migraine population (2,517 people) included patients having
      commenced specific migraine drugs, ergotamine or sumatriptan, for the first time
      from January 1 1992 to December 31 1998. The corresponding date was termed the
      'index date'. Non-migraine patients, those not having used any medication
      specific for migraine, were selected and equally matched (n=2,517). The
      cumulative incidence of initiating antidepressant treatment was estimated during
      two-year observation periods prior to and after the index date. Several
      demographic and comedication characteristics were assessed as potential
      determinants of antidepressant drug use within the migraine population. Other
      determinants included usage patterns ("therapeutic intensity") of ergotamine and
      sumatriptan, defined as the absolute number of Defined Daily Doses (DDDs)
      dispensed per patient during one year prior to initiation of antidepressant
      therapy. A total of 300 migraine patients (11.9%) and 213 non-migraine patients
      (8.5%) had initiated antidepressant treatment in the two-year period prior to or
      in the two-year period after the index date (RR adj 1.4; 95% CI 1.2-1.7). The
      cumulative incidence of initiation of antidepressant treatment for the migraine
      population was 3.0% per year prior to and 3.2% per year after the initiation of
      specific migraine analgesia. The concomitant use of benzodiazepines (RR adj 4.7;
      95% CI 3.5-6.3), migraine prophylactic medication (RR adj 2.1; 95% CI 1.6-2.8)
      and heavy therapeutic intensity use of specific migraine analgesia, defined as
      >/=150 DDDs per year were highly predictive of antidepressant drug use within the
      migraine population. In conclusion, compared to the non-migraine population, the
      initiation of antidepressant treatment was only slightly higher in the migraine
      population. A number of determinants within the latter were found to be strongly
      associated with antidepressant drug use, the nature of which most likely reflects
      an increased severity of migraine whereby therapeutic needs are higher.

PMID- 14571155
TI  - Effects of an educational compliance enhancement programme and therapeutic drug
      monitoring on treatment adherence in depressed patients managed by general
      practitioners.
AB  - Medication non-adherence is a major obstacle in the treatment of affective
      disorders. The primary objective of this study was to evaluate two different
      interventions to improve adherence to antidepressant drugs. Secondary objectives
      included response to treatment, relation between adherence and response, patient
      satisfaction and tolerability. A randomized controlled design was used to assess
      the effect of a patient educational compliance enhancing programme (CP) and
      therapeutic drug monitoring in 1031 major depressed patients treated with
      sertraline for 24 weeks and managed by their general practitioner. Adherence was
      measured by questioning, measurable serum levels of sertraline and
      desmethylsertraline, appointments kept and a composite index including all three
      methods. Treatment adherence was found in 37-70% of patients, depending on the
      method used. Neither of the interventions resulted in a significant increase in
      adherence rate. However, significantly more patients in the CP group had
      responded at week 24 compared to patients in the control group. Overall,
      significantly more adherent patients responded to treatment compared to non
      adherent patients, regardless of method used to determine adherence. This large
      study demonstrates that treatment response increases when using an educational
      compliance programme and that a strong relationship between treatment adherence
      and response exists.

PMID- 14571154
TI  - Symptom response and side-effects of olanzapine and risperidone in young adults
      with recent onset schizophrenia.
AB  - The symptom response and side-effects of olanzapine and risperidone were compared
      in patients with recent onset schizophrenia. Actively symptomatic patients (n=44)
      randomly received olanzapine 15 mg (median dose) or risperidone 4 mg (median
      dose). Symptom response and side-effects were measured during a 6-10-week
      treatment study. No major differences were observed between the two treatment
      groups. Symptoms improved significantly on the Positive and Negative Syndrome
      Scale total score, positive subscale and general psychopathology subscale for
      both treatment groups. Using five symptom dimensions, both drugs were effective
      in treating positive symptoms and agitation/excitement symptoms, and neither
      olanzapine or risperidone influenced disorganization and depression symptoms.
      Results on the negative symptoms subscale and symptom dimension were
      inconclusive. No major differences were found in the frequency of the reported
      side-effects akathisia, parkinsonism and weight gain. These data indicate that
      the differences between olanzapine and risperidone in symptom response are small.
      In spite of the relatively low power of the study, we could exclude the presence
      of substantially different treatment effects between olanzapine and risperidone.

PMID- 14571156
TI  - Reversal of antipsychotic-induced weight gain during quetiapine treatment.
AB  - Weight gain in mentally ill patients is an evident problem, and obesity can be
      two- to three-fold more prevalent in psychiatric patients than in the general
      population. We report two patients who gained weight during previous
      antipsychotic treatment but who lost weight when shifted to quetiapine.

PMID- 14571157
TI  - Quetiapine, clozapine, and olanzapine in the treatment of tardive dyskinesia
      induced by first-generation antipsychotics: a 124-week case report.
AB  - Our report of a patient with severe tardive dyskinesia (TD) who has been exposed
      to both typical antipsychotic and clozapine, olanzapine and quetiapine during a
      124-week follow-up period supports the possible beneficial effect of atypical
      antipsychotics on pre-existing symptoms of TD. Persistently high AIMS scores
      during all the periods of treatment with typical antipsychotics contrast strongly
      with the drop in scores that occurs in strict chronological sequence after
      switching to both clozapine (45%), olanzapine (27.8%) and quetiapine (85%). Since
      the reversal to haloperidol from the three atypical agents was systemically
      associated with a return to high AIMS scores, it seems likely that the
      improvement noted with clozapine, olanzapine and quetiapine represents a
      temporary symptomatic effect rather than a sustained resolution of the disorder.
      The olanzapine-clozapine-quetiapine rank order of increasing effectiveness
      against TD symptoms suggests that this property, although shared by the atypical
      antipsychotics, is to some degree drug-specific. Patient- and/or drug-dependent
      mechanisms may be involved in this gradient of effect.

PMID- 14571159
TI  - B-flow, a non-Doppler technology for flow mapping: early experience in the
      abdomen.
AB  - B-flow imaging is a non-Doppler technology for blood flow imaging that was
      introduced on high-frequency transducers at the end of the last decade. It has
      only recently become available on convex array and sector transducers suitable
      for abdominal examination. B-flow technology is not plagued by some of the
      troublesome pitfalls often encountered during color and power Doppler flow
      imaging, and appears promising as an adjunct to Doppler evaluation of blood flow
      in the abdomen. This article introduces the author's early experience using B
      flow in the abdomen, and illustrates the potential advantages this technique
      offers relative to Doppler flow mapping.

PMID- 14571160
TI  - Imaging in renal transplantation.
AB  - Renal transplantation is the best treatment option for chronic renal failure,
      with marked improvement in social activity, work, and family life. In addition to
      these obvious improvements, it is an extremely cost-effective procedure when
      successful. Ultrasonography plays a major role in the imaging of these patients,
      and ultrasound (including color Doppler) is helpful to the transplant physician
      in detecting graft dysfunction and peritransplant collections, some of which may
      be drained under ultrasound guidance. It is also helpful in the diagnosis of
      chronic vascular complications including transplant artery stenosis and
      arteriovenous fistula. It has no specific application in the diagnosis of chronic
      rejection.

PMID- 14571161
TI  - Doppler ultrasound evaluation of transjugular intrahepatic portosystemic shunt
      function: pitfalls and artifacts.
AB  - The current literature reflects controversy regarding the accuracy of Doppler
      ultrasound for the detection of transjugular intrahepatic portosystemic shunt
      (TIPS) malfunction. Experience has revealed many pitfalls and artifacts that can
      potentially interfere with the proper performance and interpretation of Doppler
      studies in patients with TIPS. In this article the author discusses and
      illustrates the spectrum of pitfalls that may be encountered during Doppler
      evaluation of TIPS function.

PMID- 14571162
TI  - Surgical local resection for early gastric cancer.
AB  - In Japan, endoscopic mucosal resection remains a familiar treatment of early
      gastric cancers even though long-term results of surgical local resection (SLR)
      including a laparoscopic or open approach have been unclear. We reviewed our SLR
      experiences. Laparoscopic wedge resection (LWR), laparoscopic intragastric
      surgery (LIS), and open local resection (OLR) were performed in 11, 7, and 11
      patients, respectively. Four LIS patients were converted to open surgery.
      Histologically, resected specimens demonstrated that larger-sized materials were
      obtained in OLR and LWR. Five patients overall showed submucosal invasion; 1
      patient underwent reoperation (gastrectomy). Long-term results showed no primary
      lesion related death; 2 patients died of other diseases. However, 2 LWR patients
      showed new lesions in the remnant stomach at 29 months and 7 years later. Both
      patients underwent subsequent gastrectomy. In conclusion, SLR is safe and
      curative for properly selected cancer patients. Precise preoperative diagnosis
      and careful remnant stomach survey is important.

PMID- 14571163
TI  - Hand-assisted laparoscopic total gastrectomy for early gastric cancer.
AB  - Laparoscopy-assisted distal gastrectomy has been applied to the treatment of
      early gastric cancer in Japan. However, there have been few reports on the
      laparoscopy-assisted total gastrectomy mainly because of the difficulty of the
      procedure. Here, we report a series of cases where hand-assisted laparoscopic
      total gastrectomies were performed successfully. The mobilization of the greater
      curvature was performed laparoscopically. About 7-cm mini-laparotomy was made at
      the epigastrium and duodenal transection was performed with linear stapler. After
      dissection of suprapyloric and anterosuperior lymph nodes was performed through
      the mini-laparotomy, dissection of lymph nodes along the celiac artery, and the
      left gastric artery was performed by hand-assisted laparoscopic surgery. Roux-en
      Y reconstruction was performed through the mini-laparotomy. We successfully
      performed this procedure in 5 patients. The mean operating time and blood loss
      were 275 minutes and 177.5 mL, respectively. Hand-assisted laparoscopic total
      gastrectomy is suitable and feasible for early gastric cancer.

PMID- 14571164
TI  - Increased gallbladder trypsin in acute cholecystitis indicates functional
      disorder in the sphincter of oddi and could make EPT a logical procedure.
AB  - Clinical and surgical observations confirm that acute cholecystitis (ACh) and
      acute biliary pancreatitis can coexist and that differentiation may be difficult
      even at surgery. Synchronous appearance of ACh and acute biliary pancreatitis
      suggests a similar etiology. Endoscopic sphincterotomy, with relief of the common
      channel outlet obstruction, has become the established therapeutical modality
      that improves the outcome in acute biliary pancreatitis. Patients suffering from
      ACh could be treated in a similar manner to prevent reflux of pancreatic juice
      into the common bile duct and the gallbladder with the intention to improve the
      clinical course. The present study investigated the presence and amount of
      pancreatic trypsin in the gallbladder bile in 73 patients operated on for
      gallstone disease with ACh and in controls. The average gallbladder bile trypsin
      level in the "edematous cholecystitis" group ranged between 0.525 and 4500 ng/mL,
      significantly exceeding that of controls, 0.5-53 ng/mL (P < 0.0001). The average
      gallbladder bile trypsin level in the "gangrenous cholecystitis" group, 0.1-71.5
      ng/mL, was within the range of controls (n.s.), most likely to be explained as a
      consequence of consumption of trypsin due to the fulminant development of the
      disease. Further controlled studies are mandatory before it would be acceptable
      to recommend endoscopic sphincterotomy as a valuable choice in the initial/early
      management of patients suffering from ACh. Such a study is underway to assess the
      possible role of obstruction at, or other disorders of, the sphincter of Oddi
      with consequent pancreatic juice reflux into the gallbladder as a possible
      initial cause of ACh.

PMID- 14571165
TI  - Increased gallbladder trypsin in acute cholecystitis indicates functional
      disorder in the sphincter of oddi and could make EPT a logical procedure.

PMID- 14571166
TI  - Impact of laparoscopy on frequency of surgery for treatment of gallstones.
AB  - Although the indications for laparoscopic cholecystectomy are generally the same
      as those for open cholecystectomy, there has been a suspicion that indications
      for cholecystectomy have broadened and the spectrum of patients undergoing this
      procedure has changed. This study was designed to determine whether surgeons and
      patients have lowered the threshold for proceeding to cholecystectomy with use of
      laparoscopic cholecystectomy. Discharge data were collected for all patients who
      underwent an elective operation in general surgery clinics in Ankara Numune
      Teaching and Research Hospital between 1990 to 2001. The rate of total
      cholecystectomy to all elective operations and rate of laparoscopic technique to
      all cholecystectomies were analyzed. Total number of operations and rate of
      cholecystectomy were relatively stable over 6 years prior to laparoscopy. With
      the introduction of laparoscopic cholecystectomy, although total number of
      elective operations seems stable, the proportion of cholecystectomy to all
      operations showed an increase. Our study could not explain the increase of total
      number of cholecystectomies since the widespread introduction of laparoscopy.
      First, it may be due to changing selection criteria for surgical treatment of
      gallstones. Second, surgery may have been done for asymptomatic gallstones. And
      third, patients with moderate symptoms who refused the (open) operation in the
      past may now be more willing to undergo a laparoscopic cholecystectomy.

PMID- 14571167
TI  - Unique features of laparoscopic cholecystectomy in Beta thalassemia patients.
AB  - Beta Thalassemia patients suffer from a high incidence of gallstones as well as
      systemic complications of iron overload. We performed laparoscopic
      cholecystectomy in 8 beta thalassemia patients and describe their specific
      features. Diagnosis was based on patients' clinical presentation and sonography.
      Trocars were readjusted due to the hepatomegaly. No intraoperative cholangiograms
      were performed. Follow-up included clinical assessment and abdominal sonography.
      All procedures were completed laparoscopically. Pigment cirrhosis and fibrosis
      around the cystic duct were noted in all patients. No biliary injury occurred.
      Post operatively, 4 patients suffered fluid leakage through the trocar site,
      treated conservatively. No major cardiopulmonary complications occurred. During a
      mean follow-up time of 65 months, all patients are symptom free and without
      evidence of biliary lithiasis. Thalassemia patients are difficult and often high
      risk patients. Improvement in anesthesia and monitoring enables better management
      of these patients. Laparoscopic cholecystectomy should be advised in carefully
      selected thalassemia patients.

PMID- 14571168
TI  - Appendix retrieval after laparoscopic appendectomy: a safe and inexpensive
      technique.
AB  - We describe a useful technique for retrieving the dissected appendix in a bag
      after laparoscopic resection. This permits laparoscopic appendectomy to be
      completed with a single 10-mm and two 5-mm (or 3-mm) ports and using only a 10-mm
      telescope. It obviates the need to change the standard 10-mm telescope to 5-mm
      scope or the extension of a smaller port incision to extract the specimen. The
      appendix was removed successfully and without complications using this technique
      in 89 consecutive laparoscopic appendectomies. The technique is safe,
      inexpensive, and uses readily available equipment.

PMID- 14571169
TI  - Recurrence rates at minimum 5-year follow-up: laparoscopic versus open sigmoid
      resection for uncomplicated diverticulitis.
AB  - The aim of the study was to compare the impact of surgical access to sigmoid
      resection on recurrence rates in patients with uncomplicated diverticulitis of
      the sigmoid (UDS) at a minimum follow-up of 5 years. Recurrence after surgery was
      defined as left lower quadrant pain, fever, and leucocytosis with consistent CT
      and enema findings on admission and at 6 weeks, respectively. Outcome measures
      included splenic flexure mobilization, specimen length, inflammation at proximal
      resection margin, and presence of teniae coli at distal resection margin. Seventy
      nine patients undergoing laparoscopic sigmoid resection (LSR) were compared with
      79 matched controls with open sigmoid resection (OSR) operated on at 2
      institutions during the same period. Patients were well matched for age, gender,
      body mass index, ASA grading, and symptoms duration, but not for follow-up length
      (81.9 versus 86.9 months, P = 0.046). Differences in rates of splenic flexure
      mobilization (19 versus 41, P < 0.001), specimen length (16.1 versus 18.3 cm, P =
      0.048), inflammation at proximal resection margin (21 versus 4, P < 0.001), and
      teniae coli at distal resection margin (4 versus 53, P < 0.001) did not show an
      impact on recurrence rates when comparison was made between LSR and OSR. Three
      LSR patients and 7 OSR patients had 1 recurrence (P = 0.19). There were no
      significant differences in rates of flexure mobilization, specimen length, and
      rates of inflammation present at proximal resection margin in 10 recurring and
      145 non-recurring patients. The rate of teniae coli present at distal resection
      margin was significantly increased in recurring patients (7 versus 43, P = 0.03).
      Median time of recurrence after surgery was 29 (range 18-74) months. Two of 11
      recurrences occurred after 5 years. Surgical access to sigmoid resection for UDS
      is unlikely to have an impact on recurrence rates provided that the oral bowel
      end is anastomosed to the proximal rectum rather than to the distal sigmoid.

PMID- 14571170
TI  - Laparoscopic anterior adrenalectomy for the treatment of adrenal metastases.
AB  - Aim of this study was to evaluate the results in 6 patients undergoing
      laparoscopic adrenalectomy for the treatment of solitary adrenal gland
      metastases. One hundred forty-five patients underwent laparoscopic adrenalectomy
      by transperitoneal anterior approach. In 6 patients the indication was the
      presence of a solitary adrenal gland metastasis. Primary tumors were the
      following: truncal melanoma, gastric cancer, renal cancer, lung cancer, and
      breast cancer. Mean age was 57 years (range 44-70 years). Three patients
      underwent right adrenalectomy and 3 patients a left adrenalectomy. No conversion
      to open surgery occurred. No mortality or intraoperative complications were
      observed. Mean operative time was 103 minutes (range 70-150) for right
      adrenalectomy and 170 minutes (range 90-280) for left adrenalectomy. No
      postoperative complications occurred. Mean diameter of the tumor was 3.5 cm
      (range 2-5 cm). Tumor free margins were obtained in every case. Mean hospital
      stay was 2 days (range 2-3 days). At follow-up, 2 patients have died of systemic
      dissemination of the disease, one 15 months and one 24 months after the
      operation. The remaining 4 patients are alive and disease free at a mean follow
      up of 7 months (range 4-11 months). So far, no port site metastases or local
      recurrence have been observed. In our experience adrenal gland metastasis can be
      treated safely and effectively by the laparoscopic transperitoneal anterior
      approach.

PMID- 14571171
TI  - Comparison of task performance of the camera-holder robots EndoAssist and Aesop.
AB  - BACKGROUND: Two robotic laparoscopic camera-holders, Endo Assist and Aesop 3000,
      are compared from a system design viewpoint measuring the time taken to perform
      certain tasks by the operator. METHODS: EndoAssist and Aesop 3000 robots were
      tested in a simulated environment. EndoAssist was controlled via a headset
      mounted motion axis selection sensor, while Aesop was voice activated. A series
      of simple and complex tasks were performed moving the camera to different
      targets. The performance of each task was video taped, and the time from onset to
      the end of the task was taken from the recording. RESULTS: The results showed the
      EndoAssist robot to be significantly quicker for most of the tasks studied. This
      was attributed to increased accuracy of movement in EndoAssist in comparison to
      the voice recognition errors evident while operating Aesop. CONCLUSION: The time
      taken to perform tasks yields significantly more information about the integrated
      human-robot system than simply studying the speed of movement of the robot.

PMID- 14571172
TI  - Thoracoscopic talc pleurodesis for recurrent, symptomatic pleural effusion
      following cardiac operations.
AB  - Seventeen patients who underwent a cardiac operation developed a recurrent,
      symptomatic pleural effusion ultimately requiring video-assisted thoracic surgery
      (VATS) and talc pleurodesis. These patients represented 0.4% of all patients
      undergoing a cardiac operation over the same time period. Compared with an age-
      and sex-matched control group of cardiac surgery patients, patients requiring
      VATS for recurrent pleural effusion were more obese with higher body mass index
      (31.9 +/- 1.2 versus 28.3 +/- 1.4 kg/M2, P = 0.03), were more likely to have
      undergone a complex cardiac operation (8/17 versus 1/17, P =.01) and were more
      frequently on anticoagulation and antiplatelet agents besides aspirin (8/17
      versus 2/17, P =.02). Patients underwent 1.86 +/- 0.34 thoracenteses with
      drainage of 846 +/- 166 mL/thoracentesis prior to referral for VATS. On average,
      patients underwent VATS 4.83 +/- 1.49 months after their cardiac operation. There
      were 3 VATS-related complications (17.6%) and no deaths. VATS talc pleurodesis
      led to symptomatic and radiologic improvement in all patients with a mean follow
      up of 8.2 +/- 1.5 months. VATS talc pleurodesis effectively and safely treats the
      unusual postcardiac surgery patient with refractory pleural effusion.

PMID- 14571173
TI  - Laparoscopic treatment of a bilobed gallbladder: a case report and review of the
      literature.
AB  - A double or bilobed gallbladder is a rare congenital anomaly. Because other
      congenital vascular and biliary duct anomalies may accompany this pathology, open
      cholecystectomy was thought to be the best treatment of symptomatic patients. In
      this paper, we report a patient with a bilobed gallbladder whose symptoms were
      successfully treated with laparoscopic cholecystectomy. We also discuss the
      characteristics and the embryology of this rare anomaly.

PMID- 14571174
TI  - Double gallbladder-a laparoscopic management.
AB  - A rare case of gallbladder duplication, an unusual biliary anomaly is reported in
      a young female patient presenting with acute cholecystitis. After a confirmed
      diagnosis of double gallbladder was made by sonography, endoscopic retrograde
      cholangio-pancreaticography (ERCP), and magnetic retrograde cholangio
      pancreaticography(MRCP), both gallbladders were removed laparoscopically. On
      histology both gallbladders showed cholesterolosis. Detailed preoperative
      investigations are required for an accurate preoperative diagnosis before
      considering laparoscopic cholecystectomy to avoid inadvertent damage to biliary
      ductal system and overlooking of second gallbladder during surgery.

PMID- 14571175
TI  - Hepatic duct confluence injury in blunt abdominal trauma: case report and
      synopsis on management.
AB  - Injuries of the extra hepatic biliary tree following blunt trauma to the abdomen
      are rare. We present here a case of injury to the confluence of the hepatic ducts
      and a brief synopsis on diagnosis and management of blunt injury to the
      extrahepatic biliary system.

PMID- 14571176
TI  - Staple line bleeding following laparoscopic splenectomy: intraoperative
      prevention and postoperative management with splenic artery embolization.
AB  - Laparoscopic splenectomy (LS) has become the procedure of choice for a variety of
      hematologic disorders and non-traumatic splenic pathology. Perioperative
      hemorrhage remains one of the most feared complications. We report 2 cases of
      postoperative splenic artery hemorrhage following vascular division using 2.5-mm
      Endo-GIA stapling cartridges. In this paper we identify and discuss important
      technical aspects of obtaining hilar vascular control during LS and report the
      first use of postoperative splenic artery embolization to control staple line
      bleeding following LS.

PMID- 14571177
TI  - A "clean" technique for managing bleeding duodenal ulcer with a new aortic
      prosthesis: endoscopic-assisted repair of bleeding duodenal ulcer.
AB  - Aortic graft infection is one of the most dreaded surgical complications. In the
      perioperative patient with fresh aortic prosthesis, this is a particularly
      complex problem. Opening the bowel changes an operation to a "clean-contaminated"
      or "contaminated" case. This increases the risk of all infectious complications
      in the patient. Theoretically, our method of repair reduces the risk of infection
      by eliminating the duodenotomy. The direct visualization with the endoscope
      replaces the need to open the potentially contaminated bowel and reduces the risk
      of bacterial translocation and bacteremia. By not opening the bowel, this keeps
      the case "clean," and likely reduces the risk of contamination and subsequent
      infection of the prosthetic graft. As the potential morbidity of aortic graft
      infection is so devastating, and now that we have the available technology and
      operative skill, we propose our technique as a potential alternative to possibly
      reduce the incidence of aortic graft infection.

PMID- 14571178
TI  - "A new instrument, the "Perfore-Aspirator" for laparoscopic treatment of hydatid
      cysts of the liver", by Zengin K, et al.

PMID- 14571179
TI  - Update on chronic hepatitis C in HIV/HCV-coinfected patients: viral interactions
      and therapy.
AB  - With highly active antiretroviral therapy (HAART), HIV-infected patients can now
      live longer and healthier lives, and other comorbid diseases, such as chronic
      hepatitis C, have emerged as a significant health concern. Coinfection with the
      hepatitis C virus (HCV) may limit life expectancy because it can lead to serious
      liver disease including decompensated liver cirrhosis and hepatocellular
      carcinoma. HCV-induced fibrosis progresses faster in HIV/HCV-coinfected persons,
      although HAART may be able to decrease this disease acceleration. Combination
      therapy for HCV with interferon and ribavirin can achieve a sustained viral
      response, although at a lower rate than in HCV-monoinfected patients. Combination
      treatment with pegylated interferon and ribavirin will probably emerge as the
      next HCV therapy of choice for HIV/HCV-coinfected patients. HCV combination
      therapy is generally safe, but serious adverse reactions, like lactic acidosis,
      may occur. Cytopenia may present a problem leading to dose reductions, but the
      role of growth factors is under study. All HIV/HCV-coinfected patients should be
      evaluated for therapy against the hepatitis C virus. A sustained viral load will
      probably lead to regression of liver disease, and even interferon-based treatment
      without viral clearance may slow down progression of liver disease. HIV/HCV
      coinfected patients who have progressed to end-stage liver disease have few
      therapeutic options other than palliative care, since liver transplants are
      generally unavailable. The mortality post-transplant may be higher than in HCV
      monoinfected patients. We are entering an era where safe and effective HCV
      therapy is being defined for HIV/HCV-coinfected patients, and all eligible
      patients should be offered treatment.

PMID- 14571180
TI  - Escape of monocyte-derived dendritic cells of HIV-1 infected individuals from
      natural killer cell-mediated lysis.
AB  - OBJECTIVE: To verify whether the in vitro sensitivity of immature dendritic cells
      (iDC) to lysis by autologous natural killer (NK) cells from HIV-infected
      individuals might be correlated with HIV disease progression. DESIGN: Both
      dendritic cells (DC) and interlekin (IL)-2 activated NK cells were obtained from
      13 HIV-infected individuals early after seroconversion and not receiving highly
      active antiretroviral therapy (HAART) and from 14 individuals with chronic HIV
      infection under HAART. The rate of NK cell-mediated killing of autologous iDC was
      correlated with classical parameters of HIV evolution. METHODS: Peripheral blood
      monocytes obtained from the Ficoll-derived leukocyte fraction after adherence to
      plastic were stimulated with granulocyte-macrophage colony stimulating factor
      plus IL-4 to induce their differentiation into iDC to be used as target cells in
      a standard 4-h cytotoxicity assay. A fraction of autologous leukocytes was
      stimulated with IL-2 to induce activation of NK cells to be used as effector
      cells. RESULTS: During early HIV infection the extent of ex vivo lysis of
      monocyte-derived DC by activated autologous NK cells was inversely and directly
      correlated with the levels of viraemia and with the percentage of circulating CD4
      T cells, respectively. In contrast, the capacity of NK cells to kill iDC was lost
      independently of the levels of plasma viraemia or the concurrence of HAART in
      chronically infected individuals. Addition of exogenous HIV Tat during the
      cytotoxicity assay inhibited NK cell-mediated lysis of DC. CONCLUSIONS: NK cell
      mediated immune surveillance against infected DC may be effective only during
      early HIV infection and may not be restored by HAART.

PMID- 14571181
TI  - Evidence for Gag p24-specific CD4 T cells with reduced susceptibility to R5 HIV-1
      infection in a UK cohort of HIV-exposed-seronegative subjects.
AB  - AIM: To characterize HIV-1 Gag p24-specific CD4 cell responses in HIV-exposed
      seronegative (ES) individuals. METHODOLOGY: Twelve ES individuals, of diverse
      ethnicity and wild type for the CCR5 Delta-32 mutation, were identified. Controls
      were HIV-negative blood donors. Gag p24-specific and total Vbeta+ CD4 cells that
      expressed MIP-1beta, IFN-gamma and IL-2 were enumerated by intracytoplasmic
      cytokine staining. beta-Chemokine expression was correlated with susceptibility
      to R5 HIV-1 infection, as measured by polymerase chain reaction for integrated
      HIV-1 and by p24 enzyme-linked immunosorbent assay. RESULTS: Similar numbers of
      mitogen-stimulated and Vbeta+ MIP-1beta+, IFN-gamma+ and IL-2+ T cells were found
      in ES and HIV-negative control subjects. However, all ES subjects tested had an
      HIV Gag p24-specific MIP-1beta+, IFN-gamma+ and IL-2+ CD4 T-cell response that
      was rare in controls. p24-Specific cells of all ES but no control subjects could
      be expanded by in-vitro Ag/IL-2 stimulation, and when re-stimulated with an
      overlapping peptide series showed evidence of a broad CD4 cell memory response
      directed against multiple regions of Gag p24. Mitogen-stimulated ES CD4 cells
      were as susceptible to HIV infection as those from control subjects, but p24
      specific IFN-gamma+ CD4 cells of six out of seven ES subjects tested were less
      susceptible to R5 HIV-1 infection than the counterpart fraction depleted of p24
      specific IFN-gamma+ cells. The addition of blocking anti-beta-chemokine
      antibodies did not promote R5 HIV-1 infection of p24-specific IFN-gamma+ cells.
      CONCLUSION: Specific CD4 cell immunity, characterized by a broadly directed
      memory Gag-p24 CD4 cell response and reduced susceptibility of specific CD4 cells
      to R5 HIV-1 infection, is a likely correlate of non-transmission.

PMID- 14571183
TI  - Detection of peripheral HIV-1-specific memory B cells in patients untreated or
      receiving highly active antiretroviral therapy.
AB  - OBJECTIVES: To examine whether polyclonal activation of circulating B cells, in a
      process that involves CD40-CD40 ligand and cytokine interactions, could induced
      HIV-1-specific memory B cells to synthesize HIV-1-specific antibodies. METHODS: B
      cells from 26 HIV-1-infected patients were cultured with a CD40L-transfected cell
      line plus interleukins 2 and 10 and tested for their secretion of HIV-1- and
      Toxoplasma gondii-specific antibodies. RESULTS: In vitro activated B lymphocytes
      from HIV-1-infected patients secreted anti-HIV-1-specific antibodies. B cells
      from HIV-1-infected patients as well as those from controls chronically infected
      by T. gondii synthesized T. gondii-specific antibodies. HIV-1-specific IgG-, IgA-
      or IgM-secreting B cells represented approximately 1 x 10(-4) to 1 x 10(-5) of
      total circulating B cells and 1 x 10(-2) to 1 x 10(-3) of immunoglobulin
      secreting cells. HIV-1-specific memory B cells were found in 9/9 untreated
      patients and in 8/17 patients receiving highly active antiretroviral therapy
      (HAART). The other nine patients showed a normal CD40-CD40L B cell response and
      six of them produced T. gondii-specific antibody B cells. The follow-up of seven
      patients indicated that HIV-1-specific memory B cells became undetectable after 8
      to 46 months of HAART, whereas T. gondii-specific memory B cells persisted in
      parasite coinfected patients. CONCLUSIONS: Circulating memory HIV-1-specific B
      cells were detected in untreated patients and in about half of the patients
      taking HAART, suggesting that persistent low-level ongoing viral replication is
      not sufficient to maintain HIV-1-specific memory B cells.

PMID- 14571182
TI  - Discordant expression of perforin and granzyme A in total and HIV-specific CD8 T
      lymphocytes of HIV infected children and adolescents.
AB  - OBJECTIVE: Perforin and granzyme are cytotoxic effector molecules that are
      believed to play essential roles in cytotoxic T cell (CTL) activity. We tested
      the hypothesis that dysregulation of these effector molecules contributes to
      defects of CD8 antiviral immune responses in pediatric subjects in chronic stages
      of perinatal HIV infection. DESIGN/METHOD: Studies of CD8 T cells were conducted
      in 33 treatment experienced HIV+ patients (median age, 10.6 years) and in 14 age
      matched healthy controls. CD8 T cells specific for HIV Gag and Pol peptides were
      identified in HLA-A2+ patients by tetramer binding assays. HIV-specific and total
      CD8 T cells were examined for perforin, granzyme and expression of CD27, a marker
      that is lost in terminally differentiated cells. RESULTS: Three populations of
      CD8 T cells were identified: granzyme+ perforin+; granzyme+ perforin- and cells
      negative for both perforin and granzyme. In HIV infected patients, granzyme+
      cells were increased in total CD8 T cells (39% versus 13% in controls) and were
      highest in HIV Gag-specific CD8 cells (42%). Perforin+ CD8 T cells were
      approximately fivefold fewer than granzyme+ CD8 T cells and were enriched in CD27
      negative cells. Most HIV-specific CD8 cells were CD27+. Granzyme expression in
      CD8 T cells correlated negatively with CD4 percentage and positively with virus
      load. CONCLUSION: A disproportionate and generalized increase in CD27+,
      granzyme+, CD8 T cells is a hallmark of established pediatric HIV infection.
      These findings support the concept of skewed maturation, with failure of CD8 T
      cells to mature into perforin-enriched, CD27-negative, effector cells.

PMID- 14571185
TI  - Lack of persistent drug-resistant mutations evaluated within and between
      treatment interruptions in chronically HIV-1-infected patients.
AB  - OBJECTIVE: To determine the effect of treatment interruptions (TI) on the
      evolution and persistence of drug-resistant viruses in chronically HIV-1-infected
      suppressed patients. METHODS: The emergence of viral resistance to combination
      antiretroviral therapy was monitored in 11 suppressed chronically HIV-1-infected
      patients undergoing from one up to four sequential TI (a total of 25 TI), by
      genotyping of the virus for known mutations in the genes for protease and reverse
      transcriptase. Resistance assays were performed at the first viral rebound > 100
      copies/ml. RESULTS: All subjects achieved resuppression of HIV-1 under the same
      antiretroviral therapy, regardless of the number of TI. Five of eleven patients
      showed no development of resistance. In the remaining six patients, the following
      patterns of mutations associated with viral resistance were found: one mutation
      (K70R), which was observed in one patient during the 1st TI and persisted during
      follow-up; two mutations (L90M, M184V), which were observed in four patients
      during the 1st TI and were intermittently present or lost following extended TI,
      treatment reinitiation and/or during subsequent TI; and evolution of two
      mutations (M184V, K219E) observed in two patients. These two mutations were not
      present during the 1st TI and were subsequently lost following therapy
      reinitiation or during the next TI. CONCLUSIONS: Detection of drug resistance
      during TI by virus genotyping assays does not predict failure to resuppress after
      antiretroviral therapy reinitiation nor persistence of a resistant viral
      population during extended interruptions or subsequent TI.

PMID- 14571184
TI  - A comparison of height and weight velocity as a part of the composite endpoint in
      pediatric HIV.
AB  - BACKGROUND: HIV adversely affects growth in children. Pediatric AIDS Clinical
      Trial Group (PACTG) protocols often use weight velocity [changes in weight z
      score for age (WAZ)] as a part of the composite endpoint for phase II and III
      clinical trials. However, WAZ and height velocity (HAZ) have not been critically
      compared for their utility as part of the composite endpoint. METHODS: HAZ and
      WAZ were compared to predict laboratory and clinical progression of HIV in a
      retrospective cohort study of HIV-infected children with data from PACTG Protocol
      300. RESULTS: In both bivariable and multivariable analyses, changes in HAZ were
      more closely linked to subsequent progression than WAZ. Children with improved
      HAZ were somewhat less likely to exhibit virological failure [odds ratio (OR),
      0.76; 95% confidence interval (CI) 0.51-1.14], than children with improved WAZ
      (OR, 1.45; 95% CI, 0.99,2.11). Children who had improved HAZ were less likely to
      exhibit immunological failure (OR, 0.7; 95% CI, 0.49-1.00), than children with
      improved WAZ (OR, 1.13; 95% CI, 0.82-1.57). Children who had improved HAZ were
      less likely to have other forms of clinical progression of HIV (OR, 0.55; 95% CI,
      0.31-0.99), than children who had improved WAZ (OR, 1.0; 95% CI, 1.58-1.94).
      CONCLUSIONS: Increases in HAZ were associated with reduced risk of subsequent
      clinical progression and subsequent immune reconstitution and weakly associated
      with declines in HIV RNA. Changes in WAZ were not associated with laboratory
      outcomes relevant to pediatric HIV infection. Height velocity should be
      considered as a component of a composite clinical endpoint in future PACTG
      trials.

PMID- 14571186
TI  - Six-year follow-up of HIV-1-infected adults in a clinical trial of antiretroviral
      therapy with indinavir, zidovudine, and lamivudine.
AB  - OBJECTIVE: To assess virological and immunological responses and toxicity in
      subjects receiving combination antiretroviral therapy. DESIGN: Six-year follow-up
      of a single arm of a randomized study of combination antiretroviral therapy.
      METHODS: HIV-infected, zidovudine-experienced patients originally randomized to
      receive indinavir, zidovudine, and lamivudine had HIV RNA levels and CD4 cell
      counts assessed over 6 years. Information was collected by questionnaire from
      subjects who discontinued the study regimen before 6 years. Both on-study and
      post-study responses were assessed. RESULTS: Of 33 subjects, 16 (48%)
      discontinued before 6 years of follow-up. After 6 years, 16 (53%) and 14 (47%) of
      30 contributing subjects had HIV RNA levels < 500 and < 50 copies/ml,
      respectively, and the median increase in CD4 cell count from baseline for 28
      contributing subjects was 268 x 10(6) cells/l. Treatment-limiting nephrolithiasis
      occurred in four subjects. Of the 16 subjects who discontinued the study, 12 had
      post-study questionnaire data available and seven had HIV RNA < 500 copies/ml on
      a post-study regimen. In an exploratory analysis combining both on-study and post
      study data at approximately 6 years, 26 (79%) and 19 (58%) of 33 had HIV RNA
      levels < 500 and < 50 copies/ml, respectively, and the median increase in CD4
      cell count from baseline was 344 x 106 cells/l. CONCLUSIONS: Antiretroviral
      therapy with indinavir, zidovudine, and lamivudine suppressed HIV viremia and
      produced continued CD4 cell increases in a majority of subjects for 6 years. Most
      subjects who discontinued study medications had HIV RNA levels suppressed on post
      study therapy. Though based on a small group, this study demonstrates the durable
      effects of antiretroviral therapy.

PMID- 14571187
TI  - Immunogenicity of an inactivated mycobacterial vaccine for the prevention of HIV
      associated tuberculosis: a randomized, controlled trial.
AB  - OBJECTIVE: Prior to the widespread use of Mycobacterium bovis, Bacille Calmette
      Guerin (BCG), inactivated whole cell mycobacterial vaccines had been shown
      effective in the prevention of tuberculosis. The present study was conducted to
      determine the safety and immunogenicity of an inactivated whole cell
      mycobacterial vaccine in persons with HIV infection.DESIGN Randomized, controlled
      trial. METHODS: A total of 39 HIV-positive patients with prior BCG immunization
      and CD4 cell counts >/= 200 x 10(6) cells/l were randomized to five doses of
      inactivated Mycobacterium vaccae (MV) vaccine or control vaccine (CV). Lymphocyte
      proliferation (LPA) and interferon gamma (IFN-gamma) responses to mycobacterial
      antigens were assayed at baseline, after three and five doses of vaccine and > 1
      year later. Parallel studies were conducted in 10 HIV-negative subjects with
      prior BCG immunization. RESULTS: Among HIV-positive patients, 19 MV recipients
      had higher LPA and IFN-gamma responses to MV sonicate than 20 CV recipients after
      three and five doses of vaccine and > 1 year later. LPA responses to
      Mycobacterium tuberculosis whole cell lysate increased over time in both groups
      consistent with prior BCG immunization and current antiretroviral therapy; after
      three doses, responses were boosted to higher levels in MV subjects than CV
      subjects. LPA responses to WCL were also boosted in HIV-negative MV recipients.
      Immunization was safe and had no adverse effects on HIV viral load or CD4 cell
      count. CONCLUSIONS: In BCG-primed, HIV-positive and HIV-negative subjects, MV
      induces durable cellular immune responses to a new mycobacterial antigen and
      boosts pre-existing responses to WCL. MV is a candidate for clinical trials for
      the prevention of HIV-associated tuberculosis.

PMID- 14571188
TI  - MCP-1-MCP-3-Eotaxin gene cluster influences HIV-1 transmission.
AB  - BACKGROUND: MCP-1 (CCL2), MCP-3 (CCL7), and eotaxin (CCL11) are genes for CC
      chemokines clustered on the long arm of chromosome 17. Previous studies have
      implicated these chemokines in monocyte recruitment, viral replication, and anti
      HIV cytotoxic T cell responses. An epidemiological analysis identified genetic
      variants influencing HIV-1 transmission and disease progression. METHODS: Genomic
      DNA from over 3000 participants enrolled in five natural history cohorts in the
      United States were analyzed. Nine single nucleotide polymorphisms (SNP) covering
      33 kb containing these three genes were genotyped using the polymerase chain
      reaction. Distortions in allele, genotype, and haplotype frequencies were
      assessed with respect to HIV-1 transmission and rates of disease progression
      using categorical and survival analyses. RESULTS: Extensive linkage
      disequilibrium was observed. Three SNP (-2136T located in the MCP-1 promoter
      region, 767G in intron 1 of MCP-1, and -1385A in the Eotaxin promoter) were
      nearly always found together on a 31 kb haplotype (H7) containing the three
      genes. Frequencies of the three variants and the H7 haplotype were significantly
      elevated (odds ratio, 0.6; P = 0.005-0.01) in uninfected European-Americans
      repeatedly exposed to HIV-1 through high-risk sexual behavior or contaminated
      blood products. CONCLUSIONS: Although the extensive linkage disequilibrium
      precludes positive identification of the causal variant, the results suggest that
      genetic variation in the H7 region influences susceptibility to HIV-1 infection.
      Since these chemokines do not bind the primary HIV-1 coreceptors CCR5 or CXCR4,
      the observed influence on transmission may result from activation of the immune
      system in response to infection rather than receptor blockage.

PMID- 14571189
TI  - Psychosocial needs, mental health, and HIV transmission risk behavior among
      people living with HIV/AIDS in St Petersburg, Russia.
AB  - OBJECTIVES: The number of new HIV infections in Russia has doubled annually since
      1996. A total of 232 424 HIV infections have been officially recorded but the
      actual number probably exceeds one million. Very little is known about the
      social, psychological, behavioral, and health care service access of persons
      living with HIV in Russia. DESIGN: A cross-sectional sample of 470 persons with
      HIV/AIDS recruited in 2002 using a representative sampling plan in major St.
      Petersburg HIV care and service agencies. METHODS: Participants completed
      anonymous self-administered questionnaires that elicited detailed information
      about social and psychological characteristics, HIV serostatus disclosure and
      discrimination experiences, and risk practices since learning of their HIV
      positive status. RESULTS: Most participants were young (mean age, 25.3 years),
      knew of their HIV positive status for about 2 years, and had histories of
      injecting drug use as well as sexual risk behavior. A large proportion reported
      encountering discrimination including being forced to sign documents
      acknowledging their HIV status (47.9%), refusal of general health care (29.6%),
      being fired from their jobs (9.9%), and being forced from their family homes
      (9.0%). Over one-third had probable clinical depression. Most remained sexually
      active since learning of their HIV positive serostatus, approximately half
      engaged in unprotected sex with HIV negative partners, and condoms were not used
      one-third of the time with discordant partners. A majority of injecting drug
      users in the sample still shared needles. CONCLUSIONS: HIV-infected persons in
      Russia experience a wide range of social, psychological, and care access
      problems. Improved services are urgently needed for persons living with HIV/AIDS
      in Russia.

PMID- 14571190
TI  - Costs of medical services for patients with HIV/AIDS in Khon Kaen, Thailand.
AB  - OBJECTIVE: To estimate the savings and cost of providing highly active
      antiretroviral therapy (HAART) to adult patients with AIDS under Universal
      Coverage (UC) in Khon Kaen Province, Thailand. DESIGN: Micro-costing of
      outpatient and inpatient services of two referral hospitals, and cost modelling.
      SETTING: Khon Kaen Regional Hospital and Northeast Regional Infectious Hospital.
      PATIENTS: Adult patients who resided in Khon Kaen and made outpatient visits at
      and/or those who were discharged from those hospitals from 1 December 2001 to 28
      February 2002. MAIN OUTCOME MEASURE: The average cost per outpatient visit and
      per inpatient day. Based on these figures, the savings and cost of providing
      HAART to adult patients with AIDS under UC at outpatient settings in this
      province were estimated. RESULTS: The average cost per outpatient visit with and
      without antiretroviral drugs (ARV) was US$294.2 and US$26.1, respectively. The
      average cost per inpatient day with and without ARV drugs was US$368.1 and
      US$43.8, respectively. The net annual cost of HAART was estimated to be US$5 674
      629. This is equivalent to 20.0% of the annual UC budget for adults in this
      province in 2002. Sensitivity analysis and projection to the year 2006 were
      conducted. CONCLUSION: A large increase in the budget would be required to
      provide HAART to all adult patients with AIDS under UC. However, the sensitivity
      analysis showed it would be an affordable policy option if low-cost
      antiretroviral drugs were successfully introduced. This type of analysis would be
      useful to assess the financial implications of providing HAART in public health
      systems worldwide.

PMID- 14571192
TI  - Survival of HIV-1 and HIV-2 perinatally infected children in The Gambia.
AB  - BACKGROUND: The risk of mother-to-child transmission (MTCT) of HIV-2 is much
      lower than that of HIV-1, but the long-term prognosis of perinatally infected HIV
      2 children is unknown. We re-visited children who were part of a large MTCT study
      in The Gambia (conducted during 1993-1997), in order to compare the long-term
      survival of children perinatally infected with HIV-2 with that of seronegative
      and of HIV-1 infected children. METHODS: Five to eight years' follow-up of a
      cohort of children born to HIV-negative, HIV-1 positive, and HIV-2 positive
      mothers. RESULTS: Seven hundred and seventy-four children were followed up for a
      median of 6.6 years. Of 17 perinatally HIV-1 infected children, three were still
      alive on 1 July 2001, two had been lost to follow-up, and 12 had died. The median
      survival was 2.5 years. Of eight HIV-2 infected children five were still alive,
      none were lost to follow-up and three had died. The mortality hazards ratio of
      both HIV-1 [9.9; 95% confidence interval (CI), 5.2-19], and of HIV-2 infected
      children (3.9; CI, 1.2-12) was significantly increased compared with children of
      seronegative mothers. The mortality hazards ratio of HIV uninfected children of
      HIV-1 or HIV-2 infected mothers was not significantly increased compared to that
      of children of seronegative mothers (P = 0.17 and P = 0.5 respectively).
      CONCLUSIONS: Children with perinatally acquired HIV-2 infection have a higher
      mortality than children of seronegative mothers. Guidelines for treatment of HIV
      1 infected children should be used for treatment of HIV-2 infected children.

PMID- 14571191
TI  - Resistance of HIV-1 to multiple antiretroviral drugs in France: a 6-year survey
      (1997-2002) based on an analysis of over 7000 genotypes.
AB  - BACKGROUND: Evaluating the proportion of patients with mutated drug-resistant HIV
      1 strains is a major issue of current AIDS research and therapy. According to a
      recent study in the United States, nearly 80% of HIV-1-infected patients have
      virus strains that are resistant to at least one antiretroviral drug. The aim of
      this study was to assess the extent of multiple drug resistance among individuals
      followed for HIV-1 infection in France. METHODS: We compiled data in a relational
      database for 3884 reverse transcriptase (2248 patients) and 3915 protease (2194
      patients) sequences of plasma samples submitted for testing between January 1997
      and March 2002 at the reference HIV AIDS hospitals located in Marseille (France).
      RESULTS: Genotypic resistance to at least one nucleoside reverse transcriptase
      inhibitor (NRTI) was present in 78.3%, resistance to at least one non-nucleoside
      reverse transcriptase inhibitor (NNRTI) was present in 38.9%, and resistance to
      at least one protease inhibitor (PI) was present in 47.0% of plasma samples. The
      proportion of patients carrying a virus with multiple resistance to three
      categories of drugs (at least one NRTI plus at least one NNRTI plus at least one
      PI) peaked at 25.9% in 2000 and stabilized at 25.5% in March 2002. CONCLUSION:
      This study demonstrates the high prevalence of drug-resistant virus in a European
      cohort of patients currently under treatment for HIV-1 infection. New therapeutic
      strategies based on a more rational use of genotypic data should be worked out to
      prevent the development of resistance.

PMID- 14571194
TI  - Increased bleeding in HIV-positive haemophiliac patients treated with lopinavir
      ritonavir.

PMID- 14571193
TI  - Evaluation of cutpoints for phenotypic hypersusceptibility to efavirenz.

PMID- 14571195
TI  - Sex differences in nevirapine disposition in HIV-infected patients.

PMID- 14571196
TI  - Multiple human papillomavirus types appear to be a feature of anal not cervical
      intra-epithelial neoplasia.

PMID- 14571197
TI  - Two cases of hypocalcemia secondary to vitamin D deficiency in an urban HIV
      positive pediatric population.

PMID- 14571198
TI  - Unusual clinical presentation of hypersensitivity reaction to abacavir.

PMID- 14571199
TI  - Extensive antiretroviral therapy resistance in an HIV-infected Zimbabwean patient
      in the UK.

PMID- 14571200
TI  - Human epithelial beta-defensins 2 and 3 inhibit HIV-1 replication.
AB  - OBJECTIVE: Mechanisms underlying mucosal transmission of HIV-1 are incompletely
      understood. We describe the anti-HIV-1 activity of human beta-defensins (hBD),
      small cationic molecules that provide protection at mucosal surfaces. METHODS AND
      RESULTS: HIV-1 induced expression of hBD-2 and -3 mRNA (but not that of hBD-1) 4-
      to 78-fold, respectively, above baseline in normal human oral epithelial cells.
      HIV-1 failed to infect these cells, even after 5 days of exposure. Recombinant
      hBD-1 had no antiviral activity, while rhBD-2 and rhBD-3 showed concentration
      dependent inhibition of HIV-1 replication without cellular toxicity. Inhibition
      was greater against CXCR4-tropic than against the CCR5-tropic HIV-1 isolates. hBD
      2 and hBD-3 induced an irreversible effect on virion infectivity, with electron
      microscopy confirming binding of hBDs to viral particles. Finally, hBD-2 and -3
      induced downmodulation of the HIV-1 coreceptor CXCR4 (but not CCR5) in peripheral
      blood mononuclear cells and T lymphocytic cells as shown by confocal microscopy
      and flow cytometry. CONCLUSIONS: This study shows for the first time that HIV-1
      induces beta-defensin expression in human oral epithelial cells and that beta
      defensins block HIV-1 replication via a direct interaction with virions and
      through modulation of the CXCR4 coreceptor. These properties may be exploited as
      strategies for mucosal protection against HIV-1 transmission.

PMID- 14571208
TI  - Challenges in evaluating methods to improve physician practice.

PMID- 14571209
TI  - Update of guidelines for the use of growth hormone in children: the Lawson
      Wilkins Pediatric Endocrinology Society Drug and Therapeutics Committee.

PMID- 14571210
TI  - Vitamin D deficiency--it's more than rickets.

PMID- 14571211
TI  - Prevention of invasive pneumococcal infection in sickle cell disease: on the
      threshold of a new era of successes?

PMID- 14571213
TI  - Socioeconomic status, schools, and adolescent depression: progress in the social
      epidemiology of adolescent health.

PMID- 14571212
TI  - Gonadotrophin-dependent [correction of dependant] precocious puberty and occult
      intracranial tumors: which girls should have neuro-imaging?

PMID- 14571214
TI  - Motivating children and adolescents to improve adherence.

PMID- 14571215
TI  - 25-hydroxyvitamin D levels among healthy children in Alaska.
AB  - OBJECTIVE: To determine vitamin D levels among children 6 to 23 months old
      receiving services from Women, Infants, and Children (WIC) programs in Alaska.
      Study design During 2001 and 2002, we recruited 133 children receiving services
      at seven WIC clinics, administered a risk factor questionnaire, and collected
      blood. RESULTS: Fifteen (11%) and 26 (20%) children, respectively, had vitamin D
      levels <15 (considered abnormal) and 15 to <25 ng/mL (low normal). Compared with
      other children, children who still breast-fed were more likely to have a vitamin
      D level <15 ng/mL (relative risk [RR], 12; 95% confidence interval [CI], 3.6-39)
      or 15 to <25 ng/mL (RR, 3.6; 95% CI, 1.9-6.8) than > or =25 ng/mL. Among 41 still
      breast-feeding children, 14 (34%) took supplemental vitamins, and six (18%) were
      reported to have received vitamins every day. CONCLUSIONS: Vitamin D deficiency
      is prevalent in Alaska. Breast-feeding in the absence of adequate vitamin D
      supplementation is the greatest risk factor.

PMID- 14571216
TI  - Invasive pneumococcal infections in children with sickle cell disease in the era
      of penicillin prophylaxis, antibiotic resistance, and 23-valent pneumococcal
      polysaccharide vaccination.
AB  - Rates and severity of pneumococcal infections in children with sickle cell
      disease were examined before licensure of pneumococcal-conjugated vaccine (PVC).
      Rates of peak invasive infection rates in 1-year-old children with hemoglobin SS
      and mortality in those 0 to 10 years of age were 36.5 to 63.4 and 1.4 to 2.8 per
      1000 person-years, respectively (>10 and 100 times as frequent as in the general
      population). Overall, 71% of serotyped isolates (n=80) were PVC serotypes and 71%
      of nonvaccine serotype strains were penicillin-sensitive. Clinical presentation
      in children with hemoglobin SS (n=71; more with hypotension) and hemoglobin SC
      (n=18; more with acute chest syndrome, otitis media) differed. Penicillin
      nonsusceptibility (38% of isolates) varied between geographic study sites.
      Penicillin prophylaxis appeared less effective against intermediate and resistant
      strains. Of all infected children, meningitis developed in 20% and 15% died
      (hemoglobin SS, n=15 and 11; hemoglobin SC, n=1 each). Factors associated with
      death included age >4 years (58%), serotype 19F, and not being followed by a
      hematologist (42% each). The pneumococcal-polysaccharide vaccine was 80.4%
      effective within 3 years after vaccination (95% CI, 39.7, 93.6). Children with
      sickle cell disease of all ages may benefit from PVC boosted with polysaccharide
      vaccination.

PMID- 14571217
TI  - Selecting girls with precocious puberty for brain imaging: validation of European
      evidence-based diagnosis rule.
AB  - OBJECTIVES: To test the sensitivities of recently published American
      recommendations predicting occult intracranial lesion (OICL) in girls with
      central precocious puberty (CPP), and to validate a previously derived diagnosis
      rule predicting OICL based on age at puberty onset and estradiol (E2) level.
      STUDY DESIGN: A retrospective, multicenter, hospital-based, cohort study was
      performed, including all girls with CPP seen in 7 centers in 6 European countries
      during given periods. American recommendations and the previously derived
      diagnosis rule were tested. RESULTS: Girls with CPP (n=443), including 35 with
      OICL, were recruited. American recommendations did not identify all OICL.
      Previously identified independent risk factors for OICL were confirmed: age <6
      years (adjusted odds ratio 20.5; 95% CI, 8.1-52.1) and E2 >45th percentile (3.0;
      95% CI, 1.3-7.1). The previously derived diagnosis rule had 100% sensitivity (95%
      CI, 90-100): all girls with OICL had either an age <6 years or an E2 level >45th
      percentile. The specificity was 39% (95% CI, 34-44). CONCLUSIONS: American
      recommendations do not seem safe to select European girls with CPP who require
      brain imaging. In settings where systematic brain imaging is not possible, the
      proposed diagnosis rule could safely help to avoid more than one third of
      unnecessary brain imaging.

PMID- 14571218
TI  - A multilevel analysis of the relation of socioeconomic status to adolescent
      depressive symptoms: does school context matter?
AB  - OBJECTIVE: To determine whether the socioeconomic context of the school
      environment is associated with adolescent depressive symptoms independent of
      individual household income. Study design Data were drawn from a 1995 nationally
      representative study of 7th to 12th grade students. Multivariable linear
      regression at the school and individual levels assessed the relation between
      income and depressive symptoms. Multilevel modeling techniques were then used to
      understand how these factors are jointly associated with adolescent depressive
      symptoms. PARTICIPANTS: Adolescents (n=13,235) in grades 7 through 12 from 132
      schools whose parent provided income information. RESULTS: Linear regression
      analyses indicated that lower household income, average school income, and
      increasing school-level income inequality were significantly (P<.001) associated
      with depressive symptoms. Further examination of these relations through
      multilevel modeling indicated that both household income (P<.01) and average
      school income (P<.05) were significantly related to depressive symptoms after
      adjusting for covariates, with evidence for an interaction between the two. The
      impact of lower household income on depressive symptoms was approximately 2-fold
      greater for students attending a poor versus a rich school. CONCLUSIONS: School
      context is associated with adolescents' depressive symptoms, even after adjusting
      for individual-level factors. The school environment may partially buffer the
      adverse influence of lower household income on adolescent depressive symptoms.

PMID- 14571219
TI  - Tales of pediatric asthma management: family-based strategies related to medical
      adherence and health care utilization.
AB  - OBJECTIVES: To examine how family management styles, garnered from parent
      interviews about the effect of asthma on family life, are related to medical
      adherence and health care utilization. STUDY DESIGN: Eighty parents with a child
      with asthma were interviewed. Computerized monitoring of medication use was
      collected every 2 months for 1 year. Parents and children completed measures of
      medical adherence and health care utilization at the time of the interview and at
      1-year follow-up. Three categories of disease management were identified:
      reactive, coordinated care, and family partnerships. Group comparisons were made
      by using analysis of variance with medical adherence and health care utilization
      as dependent variables. RESULTS: Management strategies revealed in the interview
      were distinguishable by adherence rates at the time of interview and 1 year
      after. Interview categories were also predictive of emergency department use at 1
      year follow-up. The reactive group received a diagnosis of asthma 1 year after
      noting symptoms, in contrast with the other groups, who received a diagnosis
      within 6 months. CONCLUSIONS: The use of semistructured interviews may reveal
      important information about how families manage asthma. Further work may help
      identify areas amenable to intervention and provide a better understanding of why
      some families delay treatment.

PMID- 14571222
TI  - Pulmonary fluorodeoxyglucose uptake in infants of very low birth weight with and
      without intrauterine inflammation.
AB  - OBJECTIVE: We compared early pulmonary (18)fluorodeoxyglucose ((18)FDG) uptake in
      infants who had very low birth weight with and without exposure to intrauterine
      inflammation by using positron emission tomography (PET). A secondary goal was to
      correlate (18)FDG uptake with later death or bronchopulmonary dysplasia. METHODS:
      Within 72 hours of birth, 22 singleton infants between 25 and 30 weeks of
      gestation had a thoracic PET scan after intravenous (18)FDG. Influx constants
      (K(i)) for (18)FDG were determined. Placental histology assessed exposure to
      intrauterine inflammation. RESULTS: Chorioamnionitis was found in 13 infants.
      Seven of these infants also had evidence of funisitis. No inflammation was
      detected in the remaining nine infants. Median (minimum, maximum) thoracic K(I)
      was 0.008 (0.006, 0.011) mL/min/mL in infants with funisitis, 0.006 (0.002,
      0.008) in infants with chorioamnionitis only, and 0.006 (0.001, 0.015) in infants
      with no evidence of intrauterine inflammation (P=.16). No relation was found
      between K(i) and later death or bronchopulmonary dysplasia. Cord blood
      interleukin-6 was elevated in newborns with placental inflammation (P=.014).
      CONCLUSION: Early thoracic PET scanning for metabolically active inflammatory
      cells does not differ between infants with and without exposure to intrauterine
      inflammation. Evidence of early intrapulmonary sequestration of inflammatory
      cells in some infants without chorioamnionitis points to the complex etiology of
      postnatal inflammation.

PMID- 14571221
TI  - Validation of a new biomarker of fetal exposure to alcohol.
AB  - OBJECTIVE: To test the sensitivity and specificity of fatty acid ethyl esters
      (FAEEs) extracted from meconium to identify alcohol-using pregnant women with a
      sensitive and specific methodology, gas chromatography-tandem mass spectroscopy
      (GC/MS/MS). Study design Twenty-seven samples of meconium were obtained from
      infants from the mixed race community in Cape Town, South Africa, who were
      enrolled in a longitudinal neurobehavioral study. Maternal alcohol use was
      reported prospectively during pregnancy. FAEEs were isolated from meconium and
      quantitated by GC/MS/MS. RESULTS: Ethyl oleate was the FAEE that correlated most
      strongly with maternal self-reported drinking, especially with the average ounces
      of absolute alcohol ingested per drinking day. Ethyl oleate was most strongly
      related to drinking in the second and third trimesters (Pearson r=.55 and.40,
      respectively). At a threshold of 1.5 average ounces of absolute alcohol ingested
      per drinking day, the area under the receiving operator characteristic curve
      was.92 (95% confidence interval, 0.74-0.97). Using a cut-off value of 32 ng/g,
      sensitivity was 84.2% and specificity was 83.3%. CONCLUSIONS: Ethyl oleate
      concentration in meconium assayed by GC/MS/MS provides a highly sensitive and
      specific indicator of maternal alcohol use during pregnancy.

PMID- 14571224
TI  - White matter damage and intraventricular hemorrhage in very preterm infants: the
      EPIPAGE study.
AB  - OBJECTIVE: To evaluate the prevalence of cranial ultrasound abnormalities in very
      preterm infants as a function of gestational age, plurality, intrauterine growth
      restriction, and death before discharge. STUDY DESIGN: A prospective, population
      based cohort of 2667 infants born between 22 and 32 weeks of gestation in 1997 in
      nine regions of France, transferred to a neonatal intensive care unit, for whom
      at least one cranial ultrasound scan was available. RESULTS: The frequencies of
      white matter damage (WMD), major WMD, cystic periventricular leukomalacia (PVL),
      periventricular parenchymal hemorrhagic involvement, and intraventricular
      hemorrhage with ventricular dilatation were 21%, 8%, 5%, 3%, and 3%,
      respectively. The risk of WMD increased with decreasing gestational age. Mean age
      at diagnosis of cystic PVL was older for the most premature infants.
      Intraventricular hemorrhage with ventricular dilatation was associated with a
      higher risk of cystic PVL. Intrauterine growth restriction was not associated
      with a lower prevalence of cystic PVL. CONCLUSION: The frequency of WMD is high
      in very preterm babies and is strongly related to gestational age. The incidence
      of cystic PVL did not differ between babies with intrauterine growth restriction
      and babies who were appropriate for gestational age.

PMID- 14571225
TI  - Early feeding after necrotizing enterocolitis in preterm infants.
AB  - OBJECTIVE: To report our experience with an early initiation of enteral feedings
      after necrotizing enterocolitis (NEC). STUDY DESIGN: Over a 4-year period, all
      inborn infants with NEC Bell stage II or greater received enteral feedings,
      increased by 20 mL/kg/d, once no portal vein gas had been detected on ultrasound
      for 3 consecutive days (group 1). Infants were compared with a historic
      comparison group (group 2). RESULTS: Necrotizing enterocolitis rates were 5%
      (26/523) in the early feeding group and 4% (18/436) in the comparison group. One
      early feeding infant and two comparison group infants died of NEC, whereas two
      and one, respectively, had recurrent NEC. Enteral feedings were restarted at a
      median of 4 days (range, 3-14) versus 10 days (range, 8-22) after onset of NEC.
      Early feeding was associated with shorter time to reach full enteral feedings (10
      days [range, 7-31] vs 19 days [range, 9-76], P<.001), a reduced duration of
      central venous access (13.5 days [range, 8-24] vs 26.0 days [range, 8-39],
      P<.01), less catheter-related septicemia (18% vs 29%, P<.01), and a shorter
      duration of hospital stay (63 days [range, 28-133] vs 69 days [range, 36-150],
      P<.05). CONCLUSION: Early enteral feeding after NEC was associated with
      significant benefits and no apparent adverse effects. This study was
      underpowered, however, to exclude a higher NEC recurrence risk potentially
      associated with this change in practice.

PMID- 14571227
TI  - Pulmonary function and exercise capacity for ELBW survivors in preadolescence:
      effect of neonatal chronic lung disease.
AB  - OBJECTIVE: To assess pulmonary function and exercise capacity of apparently
      asymptomatic children who were born extremely preterm. STUDY DESIGN: Pulmonary
      function and treadmill testing were performed on 50 children 9 to 15 years old
      who had birth weight <801 g (extremely low birth weight [ELBW]) and without
      apparent neurodevelopmental or pulmonary disabilities, compared with 25 children
      born at term with normal birth weight (NBW). Medical history and physical
      activity levels were assessed by parent questionnaire. Group differences were
      determined by two-sample t test. Secondary analysis was performed to assess
      significant influence of neonatal chronic lung disease (CLD) on outcome measures.
      RESULTS: Twenty percent of ELBW subjects but no subjects with NBW had clinically
      abnormal pulmonary function (>2 SD from norms, P=.026). All significant pulmonary
      function differences except peak expiratory flow rate percentages were accounted
      for by ELBW subjects who had CLD. Oxygen consumption measurements were
      significantly lower for subjects with ELBW (30.3+/-6.9 and 38.5+/-5.2 mL/kg/min,
      P=.000), independent of CLD status. CONCLUSION: Pulmonary function abnormalities
      consistent with obstructive lung disease were more frequently detected in ELBW
      children who had neonatal CLD. Low oxygen consumption measurements suggest a
      lower level of fitness for ELBW children compared with children with NBW.

PMID- 14571228
TI  - Retinal hemorrhage asymmetry in inflicted head injury: a clue to pathogenesis?
AB  - OBJECTIVE: To determine whether regional cerebral parenchymal injury patterns
      correlate with the distribution of retinal hemorrhages after inflicted head
      injury. STUDY DESIGN: Retrospective case series of funduscopic photographs and
      serial computerized tomographic imaging of 14 children with confirmed inflicted
      head injury. MAIN OUTCOME MEASURES: Retinal Hemorrhage Score per eye and per
      subject, visual field examination, regional patterns of parenchymal injury on
      computerized tomographic scans and necropsy, and retinal/optic nerve sheath
      hemorrhage distribution at necropsy. RESULTS: Ten of 14 children had retinal
      hemorrhages (71%); 90% were asymmetric (mean retinal score, 4.89 vs 2.56;
      P=.006). Retinal hemorrhages were maximal on the side of greatest cerebral injury
      in seven of 10 children initially. Subsequent imaging asymmetry predicted retinal
      hemorrhage distribution in all eight survivors. Children's Coma Scores, apnea or
      cardiorespiratory arrest, initial hemoglobin, and plasma glucose concentration
      did not predict laterality. Asymmetry was greatest if dilated ophthalmoscopy was
      performed during the first 24 hours (P=.03). Visual outcome was poor; three had
      homonymous hemianopia and four had cortical visual loss, all correlating with
      parenchymal atrophy patterns. CONCLUSION: The distribution of retinal hemorrhages
      after inflicted head injury correlates with acute and evolving regional cerebral
      parenchymal injury patterns.

PMID- 14571229
TI  - Obesity, insulin resistance, and other clinicopathological correlates of
      pediatric nonalcoholic fatty liver disease.
AB  - OBJECTIVE: To describe the clinical characteristics of nonalcoholic fatty liver
      disease (NAFLD) in children, including insulin resistance, and to test for
      correlation with liver pathology. STUDY DESIGN: A retrospective review of
      children with biopsy-proven NAFLD at Children's Hospital San Diego from 1999 to
      2002. Liver biopsy specimens were independently reviewed by two pathologists.
      RESULTS: Children with NAFLD (n=43) were mostly male (70%), Hispanic American
      (53%) and obese (88%). The criteria for insulin resistance were met by 95% of
      subjects. Steatosis was predicted by the combination of quantitative insulin
      sensitivity check index, age, and ethnicity (P<.0001). Portal inflammation was
      predicted by the combination of ALT and fasting insulin (P=.0009). Perisinusoidal
      fibrosis was predicted by the combination of AST, fasting insulin, and BMI Z
      score (P<.0001). Portal fibrosis was predicted by the combination of right upper
      quadrant pain and homeostasis model assessment of insulin resistance (P=.0028).
      CONCLUSIONS: We identified significant predictors of liver pathology in children
      with NAFLD. Children being evaluated for NAFLD should be screened for insulin
      resistance, which is nearly universal and correlates with liver histology.

PMID- 14571230
TI  - Duration of television watching is associated with increased body mass index.
AB  - OBJECTIVE: To assess the effect of television viewing on subsequent change in
      body mass index (BMI=kg/m(2)) percentiles (BMI%) in adolescence. STUDY DESIGN:
      Data were drawn from the California Teen Longitudinal Survey of adolescents 12 to
      17 years old with baseline assessment in 1993 and follow-up in 1996. Self
      reported height and weight were used to calculate BMI and derive age-specific and
      sex-specific BMI%. Hours of television watched per day were obtained at baseline
      (BTV). The relations of BTV and BMI percentiles both at baseline and after 3
      years were assessed with linear regression modeling. RESULTS: Of 2223 adolescents
      (52% male, 68% white), 5.85% (n=130) were overweight (BMI > or =95th percentile)
      at baseline and 5.40% (n=120) at follow-up. Mean BTV was 2.85 (SD, 1.98). In
      adjusted models, with each additional hour of BTV, the baseline BMI% increased
      by.9, and the follow-up BMI% increased by.47. Adolescents who watched more than 2
      hours of television a day were twice as likely to be overweight at follow-up as
      adolescents who watched < or =2 hours. CONCLUSIONS: Television viewing leads to a
      subsequent increase in BMI percentiles and overweight. Efforts to decrease
      overweight should consider interventions to reduce television time.

PMID- 14571231
TI  - Growth hormone improves height in patients with juvenile idiopathic arthritis: 4
      year data of a controlled study.
AB  - OBJECTIVE: To evaluate the efficacy and safety of growth hormone treatment in
      severely growth retarded children with juvenile idiopathic arthritis (JIA)
      receiving glucocorticoids. STUDY DESIGN: Children with systemic and polyarticular
      idiopathic arthritis (22 F, 16 M) with a mean age of 10.1 years were enrolled in
      this controlled study. Eighteen patients (9 F, 9M; mean age, 10.5 years) received
      growth hormone in a dose of 0.20 to 0.33 mg/kg body weight per week for 4 years.
      Twenty patients (13 F, 7 M; mean age, 9.6 years) served as an untreated control
      group. RESULTS: Mean improvement in height in the treated group was 1 SD, whereas
      the patients of the control group lost 0.7 SD. Disease activity markers
      correlated significantly with the mean growth velocity standard deviation score.
      In general, children with mild or moderate disease and lower comedication grew
      and responded better to growth hormone therapy than those with active disease. No
      adverse events were noted. CONCLUSION: Our data suggest that long-term growth
      hormone therapy has a beneficial effect in children with severe forms of JIA.
      Further data are needed to confirm the efficacy and safety of growth hormone and
      its effect on final height.

PMID- 14571233
TI  - Inflammation of the gastric cardia in children with symptoms of acid peptic
      disease.
AB  - OBJECTIVES: To assess the severity and causes of inflammation of the gastric
      cardia in children undergoing endoscopy for symptoms of acid peptic disease.
      STUDY DESIGN: Patients undergoing upper gastrointestinal endoscopy for symptoms
      of acid peptic disease had biopsies from gastric cardia, gastric, and esophageal
      sites, and 24-hour intraesophageal pH monitoring. Gastric cardia was defined at
      endoscopy as the anatomic zone from the squamocolumnar junction to 0.5 cm below
      it. Severity of gastric cardia inflammation was scored 0 to 9 according to
      densities of inflammatory cells and epithelial abnormalities in surface and pit
      epithelium. A score > or =2 was considered positive. RESULTS: Forty-seven
      children (median age, 6.5 years; range, 3-15) had Helicobacter pylori infection,
      gastroesophageal reflux disease (GERD), or both. In 22 patients, H pylori was
      detected in cardiac biopsies by rapid urease test and histology; it was detected
      also in the corpus and antrum in only seven of the 22. No patient had H pylori in
      gastric corpus/antrum without having the organism at the cardia as well. In 12 H
      pylori-positive patients, GERD was also diagnosed. Twenty-five patients had GERD
      and no H. pylori infection. Severity score was 3.8+/-0.8 in the H pylori group
      and 2.08+/-0.9 in the GERD alone group (P<.001); however, there was no difference
      in reflux index (24-hour % of gastroesophageal reflux) between the two groups. In
      neither group was correlation found between reflux index and severity score (H
      pylori, r=0.22; GERD alone, r=0.31; NS) nor between cardia inflammation and
      esophagitis grade (H pylori, r=0.37; GERD alone, r=0.22; NS). CONCLUSIONS: In
      children with symptoms of acid peptic disease, inflammation of the gastric cardia
      does occur. It is more severe when the cardiac zone is infected with H pylori
      than in its absence. Of major practical significance is the finding that the
      gastric cardia is a highly sensitive site for the detection of H pylori
      infection.

PMID- 14571234
TI  - Epidemiologic and clinical characteristics of children with newly diagnosed
      inflammatory bowel disease in Wisconsin: a statewide population-based study.
AB  - OBJECTIVE: To define epidemiologic and clinical characteristics of newly
      diagnosed pediatric inflammatory bowel disease (IBD) in a large population-based
      model. STUDY DESIGN: All pediatric gastroenterologists providing care for
      Wisconsin children voluntarily identified all new cases of IBD during a 2-year
      period. Demographic and clinical data were sent to a central registry
      prospectively for analysis. RESULTS: The incidence of IBD in Wisconsin children
      was 7.05 per 100,000, whereas the incidence for Crohn's disease was 4.56, more
      than twice the rate of ulcerative colitis (2.14). An equal IBD incidence occurred
      among all ethnic groups, and children from sparsely and densely populated
      counties were equally affected. The majority (89%) of new IBD diagnoses were
      nonfamilial. CONCLUSIONS: This study provides novel, prospective, and
      comprehensive information on pediatric IBD incidence within the United States.
      The surprisingly high incidence of pediatric IBD, the predominance of Crohn's
      disease over ulcerative colitis, the low frequency of patients with a family
      history, the equal distribution of IBD among all racial and ethnic groups, and
      the lack of a modulatory effect of urbanization on IBD incidence collectively
      suggest that the clinical spectrum of IBD is still evolving and point to
      environmental factors contributing to the pathogenesis.

PMID- 14571238
TI  - Images in clinical medicine: pneumatosis intestinalis.

PMID- 14571236
TI  - Palivizumab prophylaxis reduces hospitalization due to respiratory syncytial
      virus in young children with hemodynamically significant congenital heart
      disease.
AB  - OBJECTIVES: To evaluate the safety, tolerance, and efficacy of palivizumab in
      children with hemodynamically significant congenital heart disease (CHD). STUDY
      DESIGN: A randomized, double-blind, placebo-controlled trial included 1287
      children with CHD randomly assigned 1:1 to receive 5 monthly intramuscular
      injections of 15 mg/kg palivizumab or placebo. Children were followed for 150
      days. The primary efficacy end point was antigen-confirmed respiratory syncytial
      virus (RSV) hospitalization. RESULTS: Palivizumab recipients had a 45% relative
      reduction in RSV hospitalizations (P=.003), a 56% reduction in total days of RSV
      hospitalization per 100 children (P=.003), and a 73% reduction in total RSV
      hospital days with increased supplemental oxygen per 100 children (P=.014).
      Adverse events were similar in the treatment groups; no child had drug
      discontinued for a related adverse event. Serious adverse events occurred in
      55.4% of palivizumab recipients and 63.1% of placebo recipients (P<.005); none
      were related to palivizumab. Twenty-one children (3.3%) in the palivizumab group
      and 27 (4.2%) in the placebo group died; no deaths were attributed to
      palivizumab. The rates of cardiac surgeries performed earlier than planned were
      similar in the treatment groups. CONCLUSIONS: Monthly palivizumab (15 mg/kg IM)
      was safe, well-tolerated, and effective for prophylaxis of serious RSV disease in
      young children with hemodynamically significant CHD.

PMID- 14571237
TI  - Cardiac failure after initiation of insulin treatment in diabetic patients with
      beta-thalassemia major.
AB  - Diabetes mellitus is a complication of beta-thalassemia major. Two patients are
      described who developed severe cardiac failure after initiation or
      intensification of insulin treatment. We hypothesize that insulin-induced fluid
      retention combined with reduced cardiac reserve was responsible for the cardiac
      failure. Careful initiation of insulin treatment in these patients is important.

PMID- 14571239
TI  - Experiencing SARS: perspectives of the elderly residents and health care
      professionals in a Hong Kong nursing home.
AB  - Severe acute respiratory syndrome (SARS) has affected many areas of the world
      recently and is becoming a global problem. Hong Kong and China have been most
      severely affected by this new infectious disease. The elderly population is
      highly vulnerable, and mortality in those older than 65 years is more than 50%.
      In our study, 27 health care workers and 40 elderly residents in a nursing home
      were interviewed to investigate their level of knowledge of SARS and its
      prevention. Most of the elderly residents knew little regarding SARS and
      prevention strategies, despite access to outside news by TV, radio, and visitors.
      Also, the worry and fear of an outbreak of SARS among staff working in the
      nursing home was considered to be high. Tailored education programs to promote
      awareness and prevention of SARS for the elderly are needed. Also, more in
      service training, support, and counseling are strongly indicated for staff to
      promote disease prevention and improve quality of care.

PMID- 14571240
TI  - Body image disturbance in an octogenarian.

PMID- 14571241
TI  - The experience of being old-old: life after 85.

PMID- 14571242
TI  - The Older Men's Health Program and Screening Inventory: a tool for assessing
      health practices and beliefs.
AB  - Men experience greater health risks, poorer health, and shorter life expectancy
      than women.(1) However, a systematic literature review revealed no measure to
      assess the health practices and beliefs of elderly men. In response, the Older
      Men's Health Program and Screening Inventory (OMHPSI) was developed. Nursing
      practice experience and a review of literature informed instrument development.
      Subsequent to an expert panel survey and pilot-testing, the OMHPSI was completed
      by 135 community-dwelling older men and found to be an informative baseline
      assessment tool congruent with the Healthy People 2010 goal of increasing elders'
      participation in organized health promotion activities.(2) Furthermore, several
      statistically significant correlations were found between items on the OMHPSI and
      demographic variables. Of particular note, the younger participants in this study
      experienced more barriers to health-promoting behaviors (P < or =.01), had less
      healthy lifestyles (P < or =.05), and were less satisfied with their health
      behaviors (P < or =.001) compared with their older counterparts.

PMID- 14571243
TI  - Client participation to enhance socialization for frail elders.
AB  - Socialization is important throughout the life span. It provides a mode for
      enhancing a person's quality of life. This is demonstrated in a case study of a
      frail elder couple who, through use of a self-focused intervention, was able to
      develop and implement change in their socialization pattern. This study examined
      the literature, conceptualized and implemented a nursing intervention to enhance
      client participation, and evaluated outcomes within a case study framework.
      Results suggested a difference in gender socialization patterns, the importance
      of family involvement, and that the use of a focused nursing intervention may be
      effective in enhancing the lives of frail elders.

PMID- 14571244
TI  - The meaning of aging and the celebration of years among rural African-American
      women.
AB  - This study considers the meaning of aging from the perspective of a group of
      frail, rural African-American women living alone in north Florida. They defined
      aging as both an accumulation of years (eg, up-in-years old) and/or the result of
      functional impairment (eg, worn-out old). The former is a cause for celebration
      and the latter often the result of omissions or commissions on the part of the
      individual and society. Geronotologic nurses are encouraged to observe the
      client's cultural perspective and incorporate it into the plan of care and
      consider aging from many perspectives.

PMID- 14571245
TI  - Managing costly Medicare patients in the hospital.
AB  - Cost-effective strategies must be developed to address the rapidly rising number
      of hospitalized older adults. Medicare cost outliers represent substantial
      unrecovered cost to hospitals caused by limited reimbursement based on diagnosis
      related groups. A predictive model is used to identify potential cost outliers
      during admission, and a registered nurse inpatient case manager with geriatric
      expertise is the intervention to tailor the care to the unique needs of older
      adults. Community follow up is provided by social workers to complete the
      continuum. Positive outcomes from this project suggest that nursing can identify
      and successfully intervene with high-cost Medicare patients.

PMID- 14571247
TI  - Relation among stroke knowledge, lifestyle, and stroke-related screening results.
AB  - Stroke is a leading cause of individual and public health burden in the United
      States. A better understanding of the relation among stroke knowledge, lifestyle,
      and stroke-related screening results may be useful for improving prevention
      efforts. This paper assesses the relation among demographics, lifestyle, stroke
      awareness, and the presence of stroke risk factors determined by screening tests
      for a select elderly population. A population of 322 participants in the 1999
      World Senior Games received 1 or more free screening tests and completed a stroke
      awareness questionnaire. Results indicate that stroke education efforts should be
      targeted at the very elderly, those who have less than a college education, and
      those who do not have a history of chronic disease. It also may be effectively
      directed toward those with higher cholesterol.

PMID- 14571248
TI  - Fluid balance in the elderly: assessment and intervention--important role in
      community health and home care nursing.

PMID- 14571250
TI  - Gerontologic nurse practitioner care guideline: COPD in the older adult.

PMID- 14571251
TI  - Putting research into practice: health promotion activities of the old-old. What
      should one do?

PMID- 14571252
TI  - Safe medication practices: nursing assessment of medications in older adults.

PMID- 14571253
TI  - Vitamins and disease prevention.

PMID- 14571255
TI  - Differential involvement of 5-HT(1B/1D) and 5-HT6 receptors in cognitive and non
      cognitive symptoms in Alzheimer's disease.
AB  - Growing evidence suggests that a compromised serotonergic system plays an
      important role in the pathophysiology of Alzheimer's disease (AD). We assessed
      the expression of 5-HT(1B/1D) and 5-HT(6) receptors and cholinacetyltransferase
      (ChAT) activity in post-mortem frontal and temporal cortex from AD patients who
      had been prospectively assessed for cognitive function using the Mini-Mental
      State Examination (MMSE) and behavioral changes using the Present Behavioral
      Examination (PBE). 5-HT(1B/1D) and 5-HT(6) receptor densities were significantly
      reduced in both cortical areas. 5-HT(1B/1D) receptor density was correlated to
      MMSE decline in the frontal cortex, supporting its implication in memory
      impairment. The best predictor for lowered 5-HT(6) receptor density in the
      temporal cortex was the PBE measure of overactivity. The 5-HT(6)/ChAT ratio was
      related to aggression both in the frontal and temporal cortex. Therefore,
      antagonists acting at 5-HT(6) receptors could be useful in the treatment of non
      cognitive symptoms associated to AD.

PMID- 14571256
TI  - The 5-HT(6) receptor antagonist SB-271046 reverses scopolamine-disrupted
      consolidation of a passive avoidance task and ameliorates spatial task deficits
      in aged rats.
AB  - The highly potent and selective 5-HT(6) receptor antagonist SB-271046 [5-chloro-N
      (4-methoxy-3-piperazin-1-yl-phenyl)-3-methyl-2-benzothiophenesulfonamide] has
      previously been demonstrated to improve retention significantly in a spatial
      water maze paradigm in adult rats. However, SB-271046 did not have any effect on
      task acquisition. As these apparently contradictory findings may be reconciled by
      a prime influence of SB-271046 on memory consolidation, the ability of this
      compound to reverse the discrete temporal action of a cholinergic antagonist in
      the 6-h period following passive avoidance training was investigated. SB-271046,
      given orally, by gavage, 30 min prior to training Wistar rats in a step-through,
      light-dark passive avoidance task, was found to reverse significantly the amnesia
      produced by administering scopolamine (0.8 mg/kg, intraperitoneal) in the 6-h
      post-training period. The effect was dose-dependent over a range of 3-20 mg/kg.
      Further, we investigated the cognition-enhancing effects of chronic SB-271046
      administration (10 or 20 mg/kg/day; 40 days) on the acquisition and consolidation
      of a water maze spatial learning task in a population of 20-month-old Wistar rats
      with age-related learning deficits. Drug treatment progressively and
      significantly decreased platform swim angle and escape latencies over the five
      sequential trials on four consecutive daily sessions compared to vehicle-treated
      controls. SB-271046 also improved task recall as measured by significant
      increases in the searching of the target quadrant on post-training days 1 and 3,
      when the animals would have been substantially drug-free. This significant
      improvement of task recall suggests SB-271046, in addition to inducing
      symptomatic cognition-enhancing actions, also attenuates age-related decline in
      neural function.

PMID- 14571258
TI  - HERV-W-related RNA detected in plasma from individuals with recent-onset
      schizophrenia or schizoaffective disorder.

PMID- 14571257
TI  - Amphetamine primes motivation to gamble and gambling-related semantic networks in
      problem gamblers.
AB  - Previous research suggests that gambling can induce effects that closely resemble
      a psychostimulant drug effect. Modest doses of addictive drugs can prime
      motivation for drugs with similar properties. Together, these findings imply that
      a dose of a psychostimulant drug could prime motivation to gamble in problem
      gamblers. This study assessed priming effects of oral D-amphetamine (AMPH) (30
      mg) in a within-subject, counter-balanced, placebo-controlled design in problem
      gamblers (n=10), comorbid gamblerdrinkers (n=6), problem drinkers (n=8), and
      healthy controls (n=12). Modified visual analog scales assessed addictive
      motivation and subjective effects. A modified rapid reading task assessed
      pharmacological activation of words from motivationally relevant and irrelevant
      semantic domains (Gambling, Alcohol, Positive Affect, Negative Affect, Neutral).
      AMPH increased self-reported motivation for gambling in problem gamblers.
      Severity of problem gambling predicted positive subjective effects of AMPH and
      motivation to gamble under the drug. There was little evidence that AMPH directly
      primed motivation for alcohol in problem drinkers. On the reading task, AMPH
      produced undifferentiated improvement in reading speed to all word classes in
      Nongamblers. By contrast, in the two problem gambler groups, AMPH improved
      reading speed to Gambling words while profoundly slowing reading speed to
      motivationally irrelevant Neutral words. The latter finding was interpreted as
      directly congruent with models, which contend that priming of addictive
      motivation involves a linked suppression of motivationally irrelevant stimuli.
      This study provides experimental evidence that psychostimulant-like neurochemical
      activation is an important component of gambling addiction.

PMID- 14571260
TI  - Fast males.

PMID- 14571259
TI  - False discovery or missed discovery?

PMID- 14571261
TI  - Comparative genomics coming of age.

PMID- 14571262
TI  - Novel mutations in the PEX12 gene of patients with a peroxisome biogenesis
      disorder.
AB  - The peroxisome biogenesis disorders (PBDs) form a genetically and clinically
      heterogeneous group of disorders due to defects in at least 11 distinct genes.
      The prototype of this group of disorders is Zellweger syndrome (ZS), with
      neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD) as milder
      variants. Liver disease, variable neurodevelopmental delay, retinopathy and
      perceptive deafness are common to PBDs. PBD patients belonging to complementation
      group 3 (CG3) have mutations in the PEX12 gene, which codes for a protein (PEX12)
      that contains two transmembrane domains, and a zinc-binding domain considered to
      be important for its interaction with other proteins of the peroxisomal protein
      import machinery. We report on the identification of five PBD patients belonging
      to CG3. Sequence analysis of their PEX12 genes revealed five different mutations,
      four of which have not been reported before. Four of the patients have mutations
      that disrupt the translation frame and/or create an early termination codon in
      the PEX12 open reading frame predicted to result in truncated protein products,
      lacking at least the COOH-terminal zinc-binding domain. All these patients
      display the more severe phenotypes (ZS or NALD). The fifth patient expresses two
      PEX12 alleles capable of encoding a protein that does contain the zinc-binding
      domain and displayed a milder phenotype (IRD). The three biochemical markers
      measured in fibroblasts (DHAPAT activity, C26:0 beta-oxidation and pristanic acid
      beta-oxidation) also correlated with the genotypes. Thus, the genotypes of our
      CG3 patients show a good correlation with the biochemical and clinical phenotype
      of the patients.

PMID- 14571264
TI  - Spinocerebellar ataxia type 7 associated with pigmentary retinal dystrophy.
AB  - Spinocerebellar ataxia type 7 (SCA7) is an autosomal-dominant, late-onset, slowly
      progressive disorder, primarily characterized by gradual loss of motor
      coordination, resulting from dysfunction and degeneration of the cerebellum and
      its connecting pathways. The disease is caused by expansion of a CAG
      trinucleotide repeat within the SCA7 gene, which encodes a polyglutamine tract
      within a novel protein, termed ataxin-7. The expansion of polyglutamine-encoding
      CAG repeats in dissimilar genes underlies eight neurodegenerative conditions
      besides SCA7, including a number of dominant ataxias related to SCA7. Although
      elongated polyglutamine itself can initiate neuronal dysfunction and death, its
      toxicity is modulated by the context of the disease proteins, as evidenced by the
      differing clinical and pathological presentation of the various disorders. In
      this respect, it is exciting that SCA7 constitutes the only polyglutamine
      disorder, in which the photoreceptors of the retina are also severely affected,
      leading to retinal degeneration and blindness. Since the discovery of the SCA7
      mutation, numerous studies attempted to pinpoint the molecular mechanisms
      underlying the unique features of SCA7, particularly the retinal involvement.
      Here we summarize the clinical, pathological, and genetic aspects of SCA7, and
      review the current understanding of the pathogenesis of this disorder.

PMID- 14571263
TI  - An unusual arylsulfatase A pseudodeficiency allele carrying a splice site
      mutation in a metachromatic leukodystrophy patient.
AB  - A late infantile metachromatic leukodystrophy patient was found to be
      heterozygous for the arylsulfatase A (ARSA) pseudodeficiency (pd) polyadenylation
      site variant ((*)96A>G) in the absence of the commonly associated N-glycosylation
      site variant (N350S). ARSA alleles were sequenced and the genotype completely
      defined. Six sequence variations were identified, among which two resulted as
      severe disease-causing mutations, both leading to the loss of the reading frame:
      a splice acceptor site mutation in intron 4 (849-1G>A), located on the (*)96A>G
      allele and a mononucleotide deletion (258delC) in exon 2, located on the other
      allele. The altered splicing caused by the 849-1G>A mutation was shown by in
      vitro expression of a recombinant gene containing the genomic region surrounding
      the mutation. Haplotype analysis of the unusual pd allele was performed in order
      to investigate its possible origin.

PMID- 14571265
TI  - Power of QTL detection using association tests with family controls.
AB  - The power of testing for a population-wide association between a biallelic
      quantitative trait locus and a linked biallelic marker locus is predicted both
      empirically and deterministically for several tests. The tests were based on the
      analysis of variance (ANOVA) and on a number of transmission disequilibrium tests
      (TDT). Deterministic power predictions made use of family information, and were
      functions of population parameters including linkage disequilibrium, allele
      frequencies, and recombination rate. Deterministic power predictions were very
      close to the empirical power from simulations in all scenarios considered in this
      study. The different TDTs had very similar power, intermediate between one-way
      and nested ANOVAs. One-way ANOVA was the only test that was not robust against
      spurious disequilibrium. Our general framework for predicting power
      deterministically can be used to predict power in other association tests.
      Deterministic power calculations are a powerful tool for researchers to plan and
      evaluate experiments and obviate the need for elaborate simulation studies.

PMID- 14571266
TI  - Meta and pooled analysis of European coeliac disease data.
AB  - Four full genome scans have been carried out by the partners of the European
      cluster on coeliac disease as well as follow-up studies of candidate regions. No
      region outside HLA showed significant linkage to the disease in any single study.
      We first applied a meta-analysis based on a modification of Genome Screen Meta
      Analysis to take into account the different linkage statistics, the arbitrariness
      of bin cutoff points, as well as the sample size of each study. We then performed
      a pooled linkage analysis of all families and raw genotypes. Besides the HLA
      region, already known to harbour a risk factor for coeliac disease, both
      approaches leave very little doubt on the presence of a genetic risk factor in
      the 5q31-33 region. This region was suggested by several individual studies, but
      did not reach statistical values high enough to be conclusive when data sets were
      analysed separately.

PMID- 14571267
TI  - Evidence for linkage of nonsyndromic cleft lip with or without cleft palate to a
      region on chromosome 2.
AB  - Results from a genome-wide screen of 10 multiplex families ascertained through
      probands with nonsyndromic cleft lip with or without cleft palate (CL/P) in
      Mexico, Argentina, and the United States yielded suggestive evidence of linkage
      to chromosomes 2, 6, 17 and 18. Fine mapping excluded all regions except
      chromosome 2. Subsequent analysis was performed on the original 10 families plus
      an additional 16 families using 31 markers on chromosome 2. This analysis showed
      intriguing evidence of linkage to 2q (Zlr=2.26, empirical P-value=0.028 in a
      chromosome-wide analysis). Transmission disequilibrium tests also revealed
      evidence of linkage and disequilibrium for two markers in this region (D2S168 and
      D2S1400 with P-values=0.022 and 0.006, respectively). A subset of these 26
      families provided additional evidence for a susceptibility gene for CL/P on 2q,
      suggesting that further studies of genes in this region are warranted.

PMID- 14571268
TI  - The deleted in colorectal carcinoma (DCC) gene 201 R --> G polymorphism: no
      evidence for genetic association with autoimmune disease.
AB  - The product of the deleted in colorectal carcinoma (DCC) gene has a role in
      apoptosis and is a positional candidate for IDDM6, the putative chromosome 18q12
      q23 autoimmune disease locus. We hypothesised that a nonconservative substitution
      (DCC 201 R --> G; nucleotide (nt) 601 C --> G), located in an extracellular
      immunoglobulin-like domain of DCC, is an aetiological determinant of
      autoimmunity. We tested this hypothesis by genetically testing the nt 601 C --> G
      polymorphism for association with three autoimmune phenotypes in a large
      population-based case-control study. There was no evidence for association of DCC
      nt 601 C --> G with autoimmune disease in cohorts comprising 2253 subjects with
      rheumatoid arthritis, type I diabetes and Graves' disease, and 2225 control
      subjects, from New Zealand and the United Kingdom. Furthermore, using the
      transmission disequilibrium test, there was no significant evidence for biased
      transmission of the nt 601 C --> G polymorphism to probands within a 382 family
      type I diabetes affected sibpair cohort from the United Kingdom. Thus, the DCC
      201 R --> G polymorphism does not appreciably influence risk of developing the
      autoimmune diseases tested.

PMID- 14571269
TI  - Evidence for a QTL on chromosome 19 influencing LDL cholesterol levels in the
      general population.
AB  - The genetic basis of cardiovascular disease (CVD) with its complex etiology is
      still largely elusive. Plasma levels of lipids and apolipoproteins are among the
      major quantitative risk factors for CVD and are well-established intermediate
      traits that may be more accessible to genetic dissection than clinical CVD end
      points. Chromosome 19 harbors multiple genes that have been suggested to play a
      role in lipid metabolism and previous studies indicated the presence of a
      quantitative trait locus (QTL) for cholesterol levels in genetic isolates. To
      establish the relevance of genetic variation at chromosome 19 for plasma levels
      of lipids and apolipoproteins in the general, out-bred Caucasian population, we
      performed a linkage study in four independent samples, including adolescent Dutch
      twins and adult Dutch, Swedish and Australian twins totaling 493 dizygotic twin
      pairs. The average spacing of short-tandem-repeat markers was 6-8 cM. In the
      three adult twin samples, we found consistent evidence for linkage of chromosome
      19 with LDL cholesterol levels (maximum LOD scores of 4.5, 1.7 and 2.1 in the
      Dutch, Swedish and Australian sample, respectively); no indication for linkage
      was observed in the adolescent Dutch twin sample. The QTL effects in the three
      adult samples were not significantly different and a simultaneous analysis of the
      samples increased the maximum LOD score to 5.7 at 60 cM pter. Bivariate analyses
      indicated that the putative LDL-C QTL also contributed to the variance in ApoB
      levels, consistent with the high genetic correlation between these phenotypes.
      Our study provides strong evidence for the presence of a QTL on chromosome 19
      with a major effect on LDL-C plasma levels in outbred Caucasian populations.

PMID- 14571270
TI  - Is the novel SCKL3 at 14q23 the predominant Seckel locus?
AB  - Seckel syndrome (SCKL) is a rare disease with wide phenotypic heterogeneity. A
      locus (SCKL1) has been identified at 3q and another (SCKL2) at 18p, both in
      single kindreds afflicted with the syndrome. We report here a novel locus (SCKL3)
      at 14q by linkage analysis in 13 Turkish families. In total, 18 affected and 10
      unaffected sibs were included in the study. Of the 10 informative families, nine
      with parental consanguinity and one reportedly nonconsanguineous but with two
      affected sibs, five were indicative of linkage to the novel locus. One of those
      families also linked to the SCKL1 locus. A consanguineous family with one
      affected sib was indicative of linkage to SCKL2. The novel gene locus SCKL3 is
      1.18 cM and harbors menage a trois 1, a gene with a role in DNA repair.

PMID- 14571271
TI  - Mutations in NSD1 are responsible for Sotos syndrome, but are not a frequent
      finding in other overgrowth phenotypes.
AB  - Recently, deletions encompassing the nuclear receptor binding SET-Domain 1 (NSD1)
      gene have been described as the major cause of Japanese patients with the Sotos
      syndrome, whereas point mutations have been identified in the majority of
      European Sotos syndrome patients. In order to investigate a possible phenotype
      genotype correlation and to further define the predictive value of NSD1
      mutations, we performed mutational analysis of the NSD1 gene in 20 patients and
      one familial case with Sotos syndrome, five patients with Weaver syndrome, six
      patients with unclassified overgrowth/mental retardation, and six patients with
      macrocephaly/mental retardation. We were able to identify mutations within the
      NSD1 gene in 18 patients and the familial case with Sotos syndrome (90%). The
      mutations (six nonsense, eight frame shifts, three splice site, one missense, one
      in-frame deletion) are expected to result in an impairment of NSD1 function. The
      best correlation between clinical assessment and molecular results was obtained
      for the Sotos facial gestalt in conjunction with overgrowth, macrocephaly, and
      developmental delay. In contrast to the high mutation detection rate in Sotos
      syndrome, none of the patients with Weaver syndrome, unclassified
      overgrowth/mental retardation and macrocephaly/mental retardation, harbored NSD1
      mutations. We tested for large deletions by FISH analysis but were not able to
      identify any deletion cases. The results indicate that the great majority of
      patients with Sotos syndrome are caused by mutations in NSD1. Deletions covering
      the NSD1 locus were not found in the patients analyzed here.

PMID- 14571272
TI  - A missense mutation in PAX9 in a family with distinct phenotype of oligodontia.
AB  - Mutations in PAX9 have been described for families in which inherited oligodontia
      characteristically involves permanent molars. Our study analysed one large family
      with dominantly inherited oligodontia clinically and genetically. In addition to
      permanent molars, some teeth were congenitally missing in the premolar, canine,
      and incisor regions. Measurements of tooth size revealed the reduced size of the
      proband's and his father's deciduous and permanent teeth. This phenotype is
      distinct from oligodontia phenotypes associated with mutations in PAX9.
      Sequencing of the PAX9 gene revealed a missense mutation in the beginning of the
      paired domain of the molecule, an arginine-to-tryptophan amino-acid change
      occurring in a position absolutely conserved in all sequenced paired box genes. A
      mutation of the homologous arginine of PAX6 has been shown to affect the target
      DNA specificity of PAX6. We suggest that a similar mechanism explains these
      distinct oligodontia phenotypes.

PMID- 14571273
TI  - Molecular diagnosis of Huntington disease in Portugal: implications for genetic
      counselling and clinical practice.
AB  - Huntington disease (HD) is a neurodegenerative, autosomal dominant disorder of
      late-onset, caused by the expansion of a CAG repeat in the coding region of the
      gene. Ours is the reference laboratory for genetic testing in HD, in Portugal,
      since 1998; 90.1% of all 158 families known were identified for the first time,
      including patients with unusual presentation or without family history. A total
      of 338 genetic tests were performed: 234 for diagnosis, 96 for presymptomatic and
      four for prenatal testing (four were done for family studies). Most referring
      physicians were neurologists (90.6%); 82.8% of all clinical diagnosis were
      confirmed, while 83.1% of those sent for exclusion were in fact excluded. In
      presymptomatic testing, an excess of female subjects (59.4%) was again verified;
      37.5% of the consultands were found to be carriers. None of the foetuses, in four
      prenatal tests, were mutation carriers. One juvenile case was inherited from her
      mother. Our patient population is very similar to others described so far, namely
      in terms of mean age at onset and (CAG)(n) distribution, except perhaps for a
      higher frequency of large normal (class 2) alleles (3.7%). We also identify cases
      posing particular problems for genetic counselling, such as, 'homozygosity' that
      can pose a serious ethical dilemma, carriers of large normal alleles, and
      'homoallelism' for a normal gene, which will demand further procedures and may
      delay results in presymptomatic and prenatal testing.

PMID- 14571274
TI  - Karyotyping of human synaptonemal complexes by cenM-FISH.
AB  - The purpose of this work was to adapt the recently described centromere-specific
      multicolour (cenM-) FISH technique to human meiotic cells, and evaluate the
      usefulness of this multiplex fluorescence method for karyotyping human
      synaptonemal complex (SC), previously analysed by immunocytogenetic approaches.
      The results obtained demonstrate that cenM-FISH is a reliable one-single-step
      method, which allows for the identification of all SC present in pachytene
      spreads. Moreover, when cenM-FISH is applied after immunocytogenetic analysis,
      the number and distribution of MLH1 foci per chromosome can be established and
      recombination analysis for each chromosome can be performed easily.

PMID- 14571275
TI  - No evidence for involvement of IL-4R and CD11B from the IBD1 region and STAT6 in
      the IBD2 region in Crohn's disease.
AB  - Linkage studies have identified the inflammatory bowel disease (IBD)1 locus on
      chromosome 16 and the IBD2 locus on chromosome 12 to be involved in Crohn's
      disease. NOD2/CARD15 was identified as the gene of interest within the IBD1
      region. However, linkage to this region could not be explained by NOD2/CARD15
      alone. Here we set out to assess the association of additional candidate genes
      from the IBD1 and IBD2 loci with Crohn's disease using transmission
      disequilibrium testing in patient-parent triads. No significant association was
      observed with genetic variants in the genes coding for interleukin-4 receptor
      gene (IL-4R), CD11B and signal transducer and activator of transcription type 6
      (STAT6). Results for IL-4R were not affected by exclusion of all families
      carrying one of three risk alleles in NOD2. From this we conclude that IL-4R and
      CD11B in the IBD1 region and STAT6 in the IBD2 region are not involved in Crohn's
      disease in this Dutch cohort.

PMID- 14571276
TI  - Molecular genetics of exercise-induced polymorphic ventricular tachycardia:
      identification of three novel cardiac ryanodine receptor mutations and two common
      calsequestrin 2 amino-acid polymorphisms.
AB  - Mutations of two myocardial calcium signaling molecules, ryanodine receptor 2
      (RYR2) and calsequestrin 2 (CASQ2), may cause catecholaminergic polymorphic
      ventricular tachycardia (CPVT), a severe inherited arrhythmic disease manifesting
      with salvoes of exercise-induced bidirectional and polymorphic tachycardias. We
      screened 12 Finnish CPVT probands for mutations in these genes and identified
      three novel RYR2 mutations (V2306I, P4902L, R4959Q), which were absent in
      unaffected and control individuals. Although no obvious disease-causing mutations
      were identified in the CASQ2 gene, the molecular screening revealed two novel
      amino-acid polymorphisms (T66A and V76M). The frequencies of these polymorphisms
      in 185 unrelated probands with long QT syndrome and in 280 healthy blood donors
      were not significantly different. These data, combined with our previous
      findings, show that RYR2 mutations are present in at least 6/16 (38%) of the
      catecholaminergic polymorphic ventricular tachycardia families, while CASQ2
      mutations must be a rare cause of CPVT.

PMID- 14571278
TI  - Mitochondrial A12308G polymorphism affects clinical features in patients with
      single mtDNA macrodeletion.
AB  - Mitochondrial (mt)DNA alterations cause cellular energy failure and respiratory
      chain dysfunction. Single large-scale rearrangements represent the most common
      mtDNA mutations and are responsible for very variable clinical manifestations.
      Here, we show an increased frequency of the A12308G substitution, a common
      polymorphism used to define the European mtDNA haplogroup U, in mitochondrial
      patients carrying mtDNA single macrodeletion. In this group of patients, A12308G
      substitution is associated with a higher relative risk of developing pigmentary
      retinal degeneration, short stature, dysphasia-dysarthria and cardiac conduction
      defects. MtDNA haplotype might modulate the clinical expression of mitochondrial
      encephalomyopathies due to mtDNA macrodeletions.

PMID- 14571277
TI  - Parietal foramina with cleidocranial dysplasia is caused by mutation in MSX2.
AB  - The combination of skull defects in the form of enlarged parietal foramina (PFM)
      and deficient ossification of the clavicles is known as parietal foramina with
      cleidocranial dysplasia (PFMCCD). It is considered to be distinct from classical
      cleidocranial dysplasia (CCD) and is listed as a separate OMIM entry (168550). So
      far, only two families have been reported and the molecular basis of the disorder
      is unknown. We present a third family with PFMCCD, comprising four affected
      individuals in three generations, and demonstrate that a heterozygous
      tetranucleotide duplication in the MSX2 homeobox gene (505_508dupATTG) segregates
      with the phenotype. PFMCCD is indeed aetiologically distinct from CCD, which is
      caused by mutations in the RUNX2 gene, but allelic with isolated PFM, in which
      MSX2 mutations were previously identified. Our observations highlight the role of
      MSX2 in clavicular development and the importance of radiological examination of
      the clavicles in subjects with PFM.

PMID- 14571279
TI  - Propranolol cytotoxicity in rat and human lung in vitro.
AB  - Propranolol is a lipophilic nonselective beta blocker mainly eliminated via the
      liver. The specific architectural arrangement of the mammalian lung favors the
      filtration of so-called pneumophilic drugs out of the blood and retention within
      the tissue, as shown in particular for amphetamine, amiodarone, imipramine,
      chlorpromazine, propranolol and local anesthetics. In the current study we tested
      in vitro the susceptibility of freshly isolated rat type II pneumocytes (RTII),
      rat alveolar macrophages (RAM), human alveolar macrophages (HAM) and A549 human
      lung adenocarcinoma cell line (A549) to propranolol (0.001-1 mM). Cytotoxicity
      was evaluated by changes in membrane integrity (lactate dehydrogenase [LDH]
      assay) and mitochondrial metabolic activity (reduction of 3-(4,5-dimethylthiazol
      2-yl)-2,5-diphenyltetrazolium bromide, MTT) after 3-h and 20-h incubation with
      propranolol. In all tested lung cells, propranolol caused concentration-dependent
      decreases of MTT reduction and LDH retention in the fraction of attached cells,
      which was associated with an increase of LDH activity in the medium and in the
      fraction of non-attached cells. After 3-h incubation, the reduction of MTT was
      significantly decreased compared with control at > or = 1 x 10(-4) M in HAM, at >
      or = 5 x 10(-4) M in A549 and significantly decreased of LDH retention in the
      fraction of attached cells in HAM and in A549 at > or = 5 x 10(-4) M. After 20-h
      incubation the reduction of MTT was significantly decreased compared with control
      at > or = 1 x 10(-6) M in RAM, at > or = 5 x 10(-5) M in RTII and HAM and > or =
      5 x 10(-4) M in A549. Propranolol caused a significant decrease of LDH retention
      in the fraction of attached cells (> or = 5 x 10(-5) M, RAM and RTII; > or = 5 x
      10(-4) M, HAM and A549). The cytotoxic effect of propranolol in HAM and A549 was
      more pronounced after prolongation of incubation time (from 3 h to 20 h). These
      results showed that rat and human lung cells were sensitive to propranolol
      concentration < or = 1 mM in vitro. We suppose that the damaging action of
      propranolol on the lungs might be mediated by physicochemical properties of
      moiety and its pulmonary metabolites.

PMID- 14571281
TI  - Gastric mucosal lesions in influenza virus infected mice: role of gastric lipid
      peroxidation.
AB  - The present study provides direct experimental proof that the combination of
      influenza virus infection A/Aichi/2/68 (H3N3) with different models of oxidative
      stress, such as immobilization, cold and cold-restraint, is associated with
      graduated oxidative disturbances in the stomach of mice, despite the absence of
      virus replication and inflammation in this tissue. It was found that experimental
      influenza virus infection is accompanied with significant changes in gastric
      mucosal integrity, as well as an increase in the products of lipid peroxidation
      in the stomachs of mice. Preliminary exposure of mice to immobilization stress
      and subsequent inoculation of influenza virus did not significantly influence
      gastric ulceration or lipid peroxidation compared with infected mice. Cold stress
      resulted in a significant decrease in the index of stomach ulceration and did not
      influence the fluorescent products of lipid peroxidation and MDA compared with
      infected animals. The simultaneous application of cold-restraint stress and
      influenza virus infection provoked synergism in the activity of all factors on
      the parameters under investigation. Ulceration increased approximately two-fold,
      as did the amount of fluorescent products of lipid peroxidation and MDA, compared
      with influenza virus-infected and non-stressed animals.

PMID- 14571280
TI  - Role of Src in hypersensitization to phosphodiesterase inhibitors in beta2
      adrenoceptor-desensitized eosinophils.
AB  - When guinea pig eosinophils were incubated with fenoterol, a beta2-agonist, for
      120 min, not only desensitization of beta2-adrenoceptors but also
      hyperresponsiveness to phosphodiesterase (PDE) inhibitors, such as theophylline
      and rolipram, was observed. The fenoterol-induced beta2-adrenoceptor
      desensitization was not affected by pretreatment with either genistein, a broad
      spectrum tyrosine kinase inhibitor, or PP2, a specific Src family tyrosine kinase
      inhibitor. On the other hand, both genistein and PP2 abolished the
      hyperresponsiveness to PDE inhibitors in beta2-adrenoceptor-desensitized
      eosinophils. These findings suggested that Src family tyrosine kinases play
      important roles in the hypersensitization of PDE to PDE inhibitors in beta2
      adrenoceptor-desensitized eosinophils.

PMID- 14571282
TI  - Measurement of dopamine receptor-mediated jaw movements by a magnet-sensing
      system in freely moving rats.
AB  - This study tested a system for monitoring jaw movements in freely moving rats. A
      Hall-effect transducer was fixed to the skull in order to sense voltage changes
      induced by variations in the position of a magnet fixed to the mandible. By
      measuring dopamine receptor-mediated jaw movements, this system produces data
      comparable to that obtained using a light-sensitive transducer system in
      anesthetized rats, while also measuring the vertical component of jaw movements
      in freely moving rats. In combination with conventional visual observation, this
      system may provide a useful tool for assessing movements of the orofacial region
      during spontaneous and drug-evoked behavior.

PMID- 14571283
TI  - Bioavailability of two new formulations of paracetamol, compared with three
      marketed formulations, in healthy volunteers.
AB  - The aim of this study was to compare the main pharmacokinetic characteristics of
      two new paracetamol formulations, powder sachet and tablet, with that of three
      commercially available paracetamol formulations: two conventional solid tablets
      and one effervescent tablet. Twelve healthy volunteers participated in an open,
      single dose (paracetamol 1,000 mg), randomized, five-way, crossover study.
      Formulations studied included: formulation A: 2 x 500 mg paracetamol tablets
      (Laboratorios Belmac S.A.); formulation B: 1 x 1,000 mg paracetamol powder
      sachets (Laboratorios Belmac, S.A.); formulation C: 2 x 500 mg paracetamol film
      coated tablets (Panadol, SmithKline Beecham); formulation D: 2 x 500 mg
      paracetamol tablets (Tylenol, McNeil); and formulation E: 1 x 1,000 mg
      effervescent paracetamol tablets (Efferalgan, UPSA). The primary variables were
      area under the plasma concentration time curve extrapolated to infinity (AUC(0
      infinity)), maximum plasma concentration (Cmax), and time to maximum plasma
      concentration (tmax). Mean AUC(0-infinity) ranged from 52.6 (B) to 56.3 microg x
      h/ml (D); mean Cmax varied between 17.98 (C) and 20.73 microg/ml (E); mean tmax
      ranged from 0.40 (E) to 0.88 h (C); and median t(1/2) varied between 2.65 (C) and
      2.81 h (A). Formulations A, B and E showed significantly shorter tmax than
      formulation C. The tmax and Cmax values found for formulations A and B were very
      similar to that found for E, an effervescent tablet formulation. In conclusion,
      the two new formulations of paracetamol tested in this study were absorbed
      rapidly after a single oral dose in healthy volunteers, similar to an
      effervescent paracetamol formulation and significantly faster than two ordinary
      commercialized paracetamol tablets.

PMID- 14571284
TI  - Effect of concomitantly administered honey on the pharmacokinetics of
      carbamazepine in healthy volunteers.
AB  - The current study was designed to investigate the effect of concomitantly
      administered honey on the pharmacokinetics of carbamazepine in volunteers. In a
      two-way cross-over design with a one-week washout period, ten healthy volunteers
      were randomized to receive 200 mg carbamazepine orally with 30 ml of honey or
      water. Blood samples were collected at 0, 0.5, 1, 2, 3, 6, 9, 12, 24, 48 and 72 h
      after drug administration. Carbamazepine levels were estimated by high
      performance liquid chromatography (HPLC). There were no statistically significant
      differences in the various pharmacokinetics parameters when carbamazepine was
      administered with honey, compared with administration with water. In conclusion,
      carbamazepine kinetics are not altered by honey, so epileptic patients on
      carbamazepine may consume honey without the risk of an interaction.

PMID- 14571285
TI  - Role of intracardiac renin-angiotensin-aldosterone system in extracellular matrix
      remodeling.
AB  - Functional angiotensin II receptors have been documented in cardiac fibroblasts
      as well as an intracardiac aldosterone system that responds to short- and long
      term physiological stimuli. In vitro, angiotensin II increased cardiac fibroblast
      mediated collagen synthesis and mRNA levels of collagen type I, type III, pro
      alpha1 (I) collagen, pro-alpha1 (III) collagen and fibronectin, and inhibited
      matrix metalloproteinase I activity. The angiotensin II-stimulated secretion and
      expression of collagen was completely abolished by AT1 receptor antagonism, but
      not affected by AT2 receptor antagonism. In vivo, chronic infusion of angiotensin
      II increased the collagen volume fraction in the ventricles. Angiotensin
      converting enzyme (ACE) inhibition and AT1 receptor antagonism, but not AT2
      receptor antagonism, reduced collagen deposition in the myocardium in
      spontaneously hypertensive rats and in rat myocardium following myocardial
      infarction. During chronic aldosterone infusion in uninephrectomized rats on a
      high-salt diet, a marked accumulation of interstitial and to a lesser extent
      perivascular collagen occurs in the heart in both ventricles. The cardiac
      fibrosis in this aldosterone model is prevented by spironolactone. During the
      continuous infusion of aldosterone in the rat, the appearance of fibrosis was
      delayed and started 4 weeks after the beginning of the infusion, which argues
      against a direct effect of aldosterone. The mechanism of aldosterone-salt-induced
      cardiac fibrosis possibly involves angiotensin II acting through upregulated AT1
      receptors and the cardiac AT1 receptor is the target for aldosterone. An
      accumulation of collagen in the heart has also been found in patients with
      adrenal adenomas and during chronic activation of the renin-angiotensin
      aldosterone system such as in surgically-induced unilateral renal ischemia,
      unilateral renal artery banding or renovascular hypertension. Spironolactone
      prevents aortic collagen accumulation in spontaneously hypertensive rats. In
      patients with stable chronic heart failure, spironolactone treatment in addition
      to diuretics and ACE inhibition reduced circulating levels of procollagen type
      III N-terminal aminopeptide. Also, in the Randomized Aldactone Evaluation Study,
      spironolactone coadministered with conventional therapy of ACE inhibitors, loop
      diuretics and digitalis in patients with symptomatic heart failure defined as
      NYHA classes III-IV, reduced total mortality by 30%.

PMID- 14571286
TI  - Gateways to clinical trials.
AB  - Gateways to Clinical Trials is a guide to the most recent clinical trials in
      current literature and congresses. The data in the following tables has been
      retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity,
      the drug discovery and development portal, http://integrity.prous.com. This issue
      focuses on the following selection of drugs: Abetimus sodium, adefovir dipivoxil,
      AGI-1067, alefacept, alemtuzumab, ALVAC-p53, aminolevulinic acid hydrochloride,
      aminolevulinic acid methyl ester, Anti-CTLA-4 Mab, AOD-9604, apafant,
      aprinocarsen sodium, arsenic trioxide; Balaglitazone, BIM-23190, bimatoprost,
      bortezomib, bosentan, BR-1; Canertinib dihydrochloride, CDP-850, cevimeline
      hydrochloride, cinacalcet hydrochloride, clenoliximab, clevudine, CN-787; D-003,
      darusentan, deferasirox, desloratadine dexanabinol, duloxetine hydrochloride; E
      5564, edaravone, efaproxiral sodium, elvucitabine emfilermin, EN-101,
      enfuvirtide, entecavir, epithalon, eplerenone, erlotinib hydrochloride,
      escitalopram oxalate, esomeprazole magnesium, eszopiclone, etilefrine pivalate
      hydrochloride etoricoxib, everolimus, exenatide; Fidarestat, fondaparinux sodium;
      Ganstigmine hydrochloride; Homoharringtonine, HuMax-IL-15, hyperimmune IVIG;
      Imatinib mesylate, IMC-1C11, Inhaled insulin, irofulven, iseganan hydrochloride,
      ISIS-14803, ISIS-5132, ivabradine hydrochloride; Keratinocyte growth factor;
      Lafutidine, lanthanum carbonate, LAS-34475, levocetirizine, liraglutide, LY
      307161 SR; Magnesium sulfate, maribavir, melatonin, mycobacterium cell wall
      complex; NN-414, NO-aspirin, nociceptin, nolomirole hydrochloride; Olmesartan
      medoxomil oral insulin, ospemifene; PDX, perillyl alcohol, pimecrolimus,
      pitavastatin calcium, pramlintide acetate, prasterone, pregabalin, PRO-542, PV
      701, pyrazoloacridine; R-744, ranelic acid distrontium salt, rasburicase, rDNA
      insulin, resiniferatoxin, reslizumab, ridogrel, riplizumab ropivacaine,
      rosuvastatin calcium, roxifiban acetate, ruboxistaurin mesilate hydrate;
      Satraplatin, Sch-58500, semaxanib, sitaxsentan sodium, SMP-114, SU-6668;
      Teriparatide, tetrathiomolybdate, tipifarnib, tolvaptan, travoprost, treprostinil
      sodium; Valdecoxib, valganciclovir hydrochloride, vardenafil hydrochloride
      hydrate, vatalanib succinate; Ximelagatran; Z-335, ziprasidone hydrochloride,
      zoledronic acid monohydrate, ZYC-00101.

PMID- 14571287
TI  - On illness, convalescence and rehabilitation.

PMID- 14571288
TI  - A comparison of bacteremic pneumococcal pneumonia with nonbacteremic community
      acquired pneumonia of any etiology--results from a Canadian multicentre study.
AB  - BACKGROUND: Bacteremic pneumococcal pneumonia has not been the subject of a
      multicentre Canadian Study. OBJECTIVES: To compare bacteremic community-acquired
      Streptococcus pneumoniae pneumonia with nonbacteremic community-acquired
      pneumonia of any etiology. METHODS: A prospective cohort study was conducted at
      15 centres in eight Canadian provinces from January 1996 to January 1998.
      RESULTS: Fifty-six of the 450 patients (12.4%) had one or more blood cultures
      positive for S pneumoniae. Compared with the 394 blood culture-negative patients,
      the bacteremic patients were younger (55.6 years versus 63.4 years; P=0.002). At
      presentation, bacteremic patients had a higher mean oral temperature (38.1+/-1.2
      degrees C versus 37.7+/-1.2 degrees C; P=0.026), a higher pulse rate (108.4+/
      22.1 beats/min versus 102.1+/-20.6 beats/min; P=0.033), a lower diastolic blood
      pressure reading (66.8+/-12.7 mmHg versus 73.8+/-15.8 mmHg; P=0.001) and a higher
      percentage of white blood cells that were band forms (22.1% versus 14.2%;
      P=0.0007). The time from onset of symptoms until admission to hospital was
      shorter among the bacteremic patients (4.6+/-3.7 days versus 7.0+/-13.9 days;
      P=0.005). Three capsular polysaccharide types accounted for 53.4% of the
      isolates: type 14, 29.2%; type 4, 12.1%; and type 22 F, 12.1%. Two of 44 isolates
      were resistant to penicillin. CONCLUSIONS: While some differences in patient
      characteristics and presentation occur when patients with bacteremic pneumococcal
      pneumonia are compared with nonbacteremic patients with community-acquired
      pneumonia, there is considerable overlap, and clinical presentation does not
      allow one to distinguish the bacteremic patients from the nonbacteremic patients.

PMID- 14571289
TI  - Respiratory symptoms and lung function in poultry confinement workers in Western
      Canada.
AB  - OBJECTIVE: To determine whether poultry production methods impact respiratory
      health, and whether poultry farmers have more respiratory symptoms and lower lung
      function than comparison control groups. DESIGN: Cross-sectional study. SETTING:
      Provinces of Saskatchewan, Alberta and Manitoba during the winters of 1997 to
      1999. POPULATION: Three hundred three poultry workers, 241 grain farmers and 206
      nonfarming control subjects were studied. Poultry workers were further classified
      according to the poultry housing type in which they worked, ie, workers who
      worked with poultry raised on the floor (floor-based operations), which included
      broiler/roaster, broiler/breeder and turkey operations (n=181), and workers who
      worked with poultry raised in a caged setting (cage-based operations), which
      included egg operations (n=122). INTERVENTIONS: Subjects completed a respiratory
      health questionnaire, which included questions on the poultry operation and work
      habits, and participated in lung function testing. MAIN RESULTS: Overall, this
      study indicated that poultry workers report greater prevalences of current and
      chronic respiratory symptoms than control populations, and that the type of
      production method (cage-based versus floor-based) appears to influence the
      prevalence of respiratory symptoms and lung function values. Workers from cage
      based operations report greater prevalences of current cough and wheeze, as well
      as lower mean values for forced expiratory volume in the first second (FEV1),
      forced expiratory flow at 25% to 75% of vital capacity (FEF25-75) and FEV1/FVC
      than workers from floor-based facilities. Workers from cage-based facilities also
      reported greater prevalences of current and chronic cough and phlegm, as well as
      significantly lower FEF25-75 and FEV1/FVC values than nonfarming control
      subjects. Furthermore, grain farmers had lower FVC and FEV1 values than
      nonfarmers. CONCLUSIONS: The results suggest that the type of poultry production
      system (ie, floor- versus cage-based) appears to have an effect on the
      respiratory response of workers from these facilities. Further studies are
      required to understand the physiological mechanisms of respiratory dysfunction
      and the relationships concerning workplace exposure among poultry workers.

PMID- 14571290
TI  - A case for rimantadine to be marketed in Canada for prophylaxis of influenza A
      virus infection.
AB  - PURPOSE: To evaluate the efficacy and safety of amantadine and rimantadine, the
      first generation antivirals, for the prophylaxis of influenza virus. DATA
      SOURCES: A systematic search of the English language literature using MEDLINE,
      EMBASE, Current Contents and the Cochrane database from 1966 to April 2002, as
      well as a manual search of references from retrieved articles, were performed.
      STUDY SELECTION: Prospective, randomized, controlled clinical trials evaluating
      amantadine and rimantadine for prophylaxis of naturally occurring influenza A
      illness were considered. The control arm used either a placebo or an antiviral
      agent. DATA EXTRACTION: Each trial was assessed by two authors to determine the
      adequacy of randomization and description of withdrawals. Efficacy data were
      extracted according to a predefined protocol. Discrepancies in data extraction
      among the investigators were solved by consensus. Nine prophylaxis studies of
      amantadine and rimantadine met the criteria for this systematic review. DATA
      SYNTHESIS: Seven amantadine versus placebo trials (n=1797), three rimantadine
      versus placebo trials (n=688) and two amantadine versus rimantadine studies
      (n=455) were included for the meta-analysis on the prevention of influenza A
      illness. The summary of results for the relative odds of illness indicated a 64%
      reduction in the amantadine group compared with placebo (OR 0.36, 95% CI 0.23 to
      0.55, P< or =0.001), a 75% reduction in illness for the rimantadine group
      compared with placebo (OR 0.25, 95% CI 0.07 to 0.97, P=0.05) and no significant
      differences in the odds of illness for the amantadine versus rimantadine groups
      (OR 1.15, 95% CI 0.57 to 2.32, P=0.32). The summary of results examining adverse
      events showed significantly higher odds of central nervous system adverse
      reactions and premature withdrawal from the clinical trials in the amantadine
      treated group than in the placebo-treated group. Compared with the placebo
      treated group, the rimantadine-treated group did not have a significantly higher
      rate of withdrawal or central nervous system events. However, there was a
      significant increase in the odds of gastrointestinal adverse events for those
      treated with rimantadine compared with those treated with placebo (OR 3.34, 95%
      CI 1.17 to 9.55, P=0.03). In the comparative trials of amantadine to rimantadine,
      rimantadine was associated with an 82% reduction in the odds of central nervous
      system events (OR 0.18, 95% CI 0.03 to 1.00, P=0.05) and a 60% reduction in the
      odds of discontinuing treatment (OR 0.40, 95% CI 0.20 to 0.79, P=0.009).
      CONCLUSION: This meta-analysis demonstrates that amantadine and rimantadine are
      superior to placebo in the prevention of influenza A illness. Both antiviral
      agents have an increased number of adverse events compared with placebo; however,
      the use of amantadine is associated with significantly higher numbers of central
      nervous system events and treatment withdrawals compared with rimantadine. Thus,
      rimantadine should be the preferred agent in this class for the prevention of
      influenza A virus infection and should be made available in Canada.

PMID- 14571291
TI  - Pulmonary sclerosing hemangioma with lymph node metastases.
AB  - Pulmonary sclerosing hemangioma is an unusual benign tumour of uncertain
      histogenesis. In the past 50 years, hundreds of cases have been described. A case
      of sclerosing hemangioma with some unusual features, including a false-positive
      fine needle aspiration biopsy and histological evidence of lymph node metastases,
      is described.

PMID- 14571292
TI  - Mediastinal synovial sarcoma: a case report and literature review.
AB  - Synovial sarcomas are uncommon soft tissue tumours. Immunohistochemistry and
      cytogenetic techniques are essential for proper diagnosis and differentiation
      from other spindle cell neoplasms. A case of mediastinal synovial sarcoma is
      described, of which the unusual location, diagnosis and treatment form the basis
      of this report.

PMID- 14571293
TI  - The enteric nervous system in inflammation and pain: the role of proteinase
      activated receptors.
AB  - The enteric nervous system (ENS) plays a pivotal role in inflammatory and
      nociceptive processes. Drugs that interact with the ENS have recently raised
      considerable interest because of their capacity to regulate numerous aspects of
      the gut physiology and pathophysiology. The present article summarizes recent
      research on proteinases and proteinase-activated receptors (PARs) as signalling
      molecules in the ENS. In particular, experiments in animal models suggest that
      PAR2 is important to neurogenic inflammation in the intestine. Moreover, PAR2
      agonists seem to induce intestinal hypersensitivity and hyperalgesic states,
      suggesting a role for this receptor in visceral pain perception. Thus, PARs,
      together with the proteinases that activate them, represent exciting new targets
      for therapeutic intervention on the ENS.

PMID- 14571294
TI  - Hepatocellular carcinoma presenting as right supraclavicular lymphadenopathy.
AB  - Two patients, one with previously undiagnosed liver disease, presenting with
      right supraclavicular lymphadenopathy were subsequently diagnosed with
      hepatocellular carcinoma. This presentation has only been previously described
      once, and the mechanism of this unusual presentation is discussed.

PMID- 14571295
TI  - Training the gastroenterologist of the future: a different mix of knowledge,
      skills and attitudes is needed.
AB  - In the United States, the declining interest of residents in gastroenterology is
      thought to be the result of the specialty being too procedure driven and not
      intellectually challenging. It is clear that the growth of technology and
      excessive demands for procedures have forced the curtailing of clinic time,
      erosion of clinical skills, distraction from scholarly pursuits and a decrease in
      the intellectual content of our training programs. In order to attract the 'best
      and the brightest' and to better prepare gastroenterologists for the future,
      trainees will require more knowledge and experience in nutrition, genetics and
      the evaluative sciences. Furthermore, they need to realize that the main
      responsibility of clinicians is problem solving. This can be learned only through
      personal clinical experience and teaching by clinicians with good analytical and
      intuitive skills. Quality care requires the integration of the needs, means and
      preferences of patients with evidence-based medical practice. Finally, new
      physicians should be imbued with the concept that an empathic relationship with
      patients is crucial for the accurate collection of information and plays an
      important therapeutic role.

PMID- 14571296
TI  - Perhaps the time has come.

PMID- 14571297
TI  - Viral hepatitis in a Canadian First Nations community.
AB  - Serological markers for hepatitis A (HAV), B (HBV) and C (HCV) were documented in
      315 inhabitants (27%) of a central Manitoba First Nations community. Serologic
      evidence of HAV infection (anti-HAV positive) was almost universal (92%) by the
      age of 20 years. HBV infection (antibody to hepatitis B core antigen positive)
      had occurred in only 2.3% of the study population and no chronic carriers were
      identified. Serological evidence of HCV infection (anti-HCV positive) was
      documented in 2.2% of the population but ongoing viremia (HCV-RNA positive by
      polymerase chain reaction) was absent. The results of this study highlight the
      importance of universal HAV vaccination; likely reflect the efficacy of existing
      prenatal screening and immunoprophylaxis programs for HBV; and raise the
      possibility that First Nations peoples have an enhanced ability to spontaneously
      clear HCV.

PMID- 14571300
TI  - The need for a different cholesterol lowering drug.

PMID- 14571298
TI  - Quality of life assessment after pancreatic enzyme replacement therapy in chronic
      pancreatitis.
AB  - GOALS: To evaluate the quality of life (QoL) of patients with chronic
      pancreatitis before and after pancreatic enzyme replacement therapy in a
      prospective, multicentre, follow-up study. STUDY: Two groups of patients were
      evaluated. Group 1 consisted of 31 patients with newly diagnosed chronic
      pancreatitis who had never been treated with pancreatic enzyme preparations.
      Group 2 consisted of 39 patients whose disease was diagnosed on average 3.4 years
      before the start of the study. The latter group of patients had undergone
      pancreatic enzyme replacement therapy, but during follow-up this treatment proved
      to be insufficient. The dose of pancreatic enzyme replacement therapy was
      tailored in accordance with the degree of pancreatic exocrine insufficiency
      measured by means of exocrine pancreatic function tests. A modified European
      Organizaton for Research and Treatment of Cancer Quality of Life Questionnaire
      Core 30 (EORTC QLQ-C30) was used to assess QoL. RESULTS: The social functioning
      and financial strain were significantly better, while the levels of hope and
      confidence were significantly reduced in group 1 compared with group 2. A
      significant gain in body weight and a significantly reduced defecation rate were
      found in both groups one month after the beginning of the pancreatic enzyme
      replacement therapy when compared with the pretreatment values. The prevalence of
      general and disease-specific symptoms and the intensity of pain were reduced in
      both groups after one month of enzyme substitution therapy. The working ability,
      the financial strain and the overall QoL scores were improved significantly in
      both groups, while the cognitive functioning score was found to be significantly
      improved during the follow-up only in group 1. The overall increase in the QoL
      score correlated significantly with the increase in body weight and the decrease
      in defecation number in both groups. CONCLUSIONS: Pancreatic enzyme replacement
      therapy in patients with chronic pancreatitis not only reduced the extent of
      steatorrhea and pain, but also significantly improved a variety of other symptoms
      and the patient's QoL. Individually tailored enzyme replacement therapy improved
      the QoL not only in the untreated chronic pancreatitis patients, but also in the
      inadequately treated group. This study demonstrated that the EORTC QLQ-C30
      questionnaire, with the addition of two further questions about steatorrhea, is a
      useful tool for the evaluation of QoL in patients with chronic pancreatitis.

PMID- 14571301
TI  - Ezetimibe and cholesterol absorption.
AB  - Cholesterol, an important biological lipid and excessive dietary intake, is
      associated with hypercholesterolemia, a prevalent cardiovascular risk factor.
      Because cholesterol is essentially a water insoluble molecule, its transport
      within and absorption from the aqueous medium of the intestine is rather complex.
      This takes place in a series of orderly and interrelated steps, including
      emulsification, hydrolysis by specific pancreatic esterases, micellar transport,
      mucosal absorption, resynthesis in enterocytes and assembly with apolipoproteins
      to form chylomicrons. Many of these processes are not well characterized at the
      molecular level. Besides being generally inefficient, cholesterol absorption is
      highly variable with a between-subject variability that depends in part on
      genetic factors and an intraindividual variability, which may be modulated by
      physiological and dietary conditions. All of the sequential steps in intestinal
      cholesterol absorption can be interfered with by dietary components or drugs and
      therefore are potential therapeutic targets for rendering cholesterol absorption
      even more inefficient in an attempt to lower cholesterol levels.

PMID- 14571302
TI  - Clinical use of ezetimibe.
AB  - Despite advances in pharmacological therapies to treat and prevent cardiovascular
      disease, it remains the leading cause of death in Canada. There now exists a
      large body of evidence demonstrating that reduction of low-density lipoprotein
      cholesterol (LDL-C) effectively reduces cardiovascular morbidity and mortality.
      Despite this, a large proportion of patients who would benefit from this
      intervention are still not achieving the recommended LDL-C levels. The currently
      available pharmacological agents, especially statins, are very effective but have
      rare, yet potentially significant, side effects. The likelihood of these side
      effects is small but does increase with increasing drug dose. As a result,
      dosages are often not titrated upward because they cannot be tolerated or their
      side effects are feared by either physicians or patients. Ezetimibe is a new
      cholesterol absorption inhibitor that is safe and effective in total cholesterol
      and LDL-C reduction. When used as monotherapy or in combination with a statin,
      ezetimibe has been shown to reduce LDL-C by an additional 15% to 20% and improve
      high-density lipoprotein cholesterol and triglycerides slightly. The addition of
      ezetimibe to a statin produces an LDL-C reduction of similar magnitude to a three
      fold increase in statin dose. The combination of ezetimibe and either
      atorvastatin or simvastatin has also been found to be beneficial in patients with
      homozygous familial hypercholesterolemia. The safety profile is similar to
      placebo and no significant drug interactions have been observed. There is no
      clinical trial outcome evidence associated with the use of ezetimibe at this
      time. Thus, ezetimibe is a safe and effective addition to the current LDL-C
      lowering regimen and is most useful in those patients who cannot achieve
      sufficient LDL-C reduction with an adequate dose of statin alone, cannot tolerate
      a statin or are fearful of a statin.

PMID- 14571303
TI  - Dietary cholesterol, cholesterol absorption, postprandial lipemia and
      atherosclerosis.
AB  - The relationship among dietary cholesterol, cholesterol absorption, the
      metabolism of cholesterol-rich chylomicron remnants and atherosclerosis is
      complex; however, recent advances have provided insight into the mechanisms
      involved. Although dietary cholesterol is an independent risk factor for
      atherosclerosis, the attributable risk is low compared with dietary variables
      such as the amount and type of fat. Clinical studies have demonstrated that in
      humans consuming a typical Western-type diet, decreasing the amount of dietary
      cholesterol intake results in only small changes in low-density lipoprotein (LDL)
      cholesterol and little or no change in the ratio of total cholesterol to high
      density lipoprotein cholesterol. These findings are better appreciated when all
      sources of cholesterol entering the intestinal lumen are considered. Only a third
      of intestinal cholesterol per day is derived from the diet. Cholesterol from
      endogenous sources, including the bile and intestinal epithelial cells,
      represents the majority of cholesterol absorbed and subsequently formed into
      chylomicrons and secreted into the circulation. There is increasing evidence that
      postprandial lipoproteins are atherogenic, in particular, cholesterol-rich
      chylomicron remnants. These lipoproteins have the capacity to enter the arterial
      wall and promote atherogenesis at several stages of development, including the
      induction of smooth muscle cells and macrophage foam cell formation. Furthermore,
      enhanced delivery of chylomicron remnants to the liver decreases hepatic LDL
      receptor expression, resulting in increased plasma LDL concentrations. Therefore,
      the inhibition of cholesterol absorption has become an attractive therapeutic
      target. There is growing genetic and biochemical evidence that intestinal
      cholesterol absorption is carrier-mediated, which has facilitated the development
      and characterization of small molecule inhibitors of this process. Ezetimibe, the
      first of these new compounds, inhibits intestinal absorption of dietary and
      biliary cholesterol and lowers total and LDL-cholesterol concentrations in
      plasma. By inhibiting cholesterol absorption, and possibly by reducing the
      cholesterol content of chylomicrons, ezetimibe may decrease the atherogenic
      potential of chylomicron remnants.

PMID- 14571304
TI  - The pharmacokinetics of ezetimibe.
AB  - Ezetimibe is the first member of a new class of selective cholesterol absorption
      inhibitors. The drug and its active glucuronide metabolite impair the intestinal
      reabsorption of both dietary and hepatically excreted biliary cholesterol through
      inhibition of a membrane transporter yet to be identified. Absorption of
      ezetimibe is rapid and not altered by food content following oral administration.
      The drug is not metabolized by the cytochrome P450 system but extensive
      glucuronidation takes place in the intestine. Consequently, plasma concentrations
      of ezetimibe represent approximately 10% of total ezetimibe in plasma.
      Enterohepatic recirculation observed for ezetimibe and its glucuronimide
      significantly increases the residence time of these compounds in the intestine,
      at their site of action. Elimination of ezetimibe glucuronimide appears impaired
      in elderly patients and patients with renal insufficiency with plasma
      concentrations increased 1.5- to 2-fold. So far, no drug interaction study has
      been associated with major changes in either the pharmokinetics of ezetimibe or
      coadministered drugs.

PMID- 14571305
TI  - The electronic health record.

PMID- 14571307
TI  - The contemporary dinosaur.

PMID- 14571308
TI  - Surveillance at work: zeroing in on cardiovascular diseases in regional health
      units across Canada.

PMID- 14571309
TI  - Regional variations in cardiovascular mortality in Canada.
AB  - BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death in Canada
      with wide, unexplained regional variations in heart disease mortality. However,
      no studies to date have explored the relationship between a number of health
      region characteristics and regional variation in heart disease mortality rates
      across Canada. INTRODUCTION: We studied the contribution of various traditional
      cardiac risk factors, social determinants of health and other community
      characteristics to regional variations in heart disease mortality rates across
      Canada. METHODS: Cardiovascular disease and ischemic heart disease (IHD) age
      standardized mortality rates were obtained from Statistics Canada for three years
      - 1995 to 1997. Health region characteristics were taken from the 2000/2001
      Canadian Community Health Survey, and the 1996 Canadian Census and the Labour
      Force Survey. Linear regression analyses and analyses of variance were employed
      to identify relationships between these health region characteristics and CVD and
      IHD mortality rates. RESULTS: Significant regional variations in CVD mortality
      rates per 100,000 population were observed. Newfoundland and Labrador had the
      highest CVD and IHD mortality rates, while Nunavut and the Northwest Territories
      had the lowest CVD and IHD mortality rates. Health region smoking and
      unemployment rates were identified as the most important factors associated with
      CVD and IHD mortality at the health region level. CONCLUSIONS: Significant
      regional variations in age-standardized CVD and IHD mortality were noted both at
      the provincial/territorial level and the health region level. Efforts to reduce
      CVD and IHD mortality in Canada require attention to both traditional risk
      factors (eg, smoking) and broader determinants of health (eg, unemployment
      rates).

PMID- 14571310
TI  - Risk factors for cardiovascular disease in Canada.
AB  - BACKGROUND: This paper provides an update of the prevalence of important
      cardiovascular disease (CVD) risk factors in subgroups of the Canadian
      population. To improve awareness of the impact of CVD risk factor variations on
      disease burden, smoking-attributable mortality (SAM) has been estimated for the
      first time for each health region in Canada. METHODS: The 2000/01 Canadian
      Community Health Survey (CCHS) was used to estimate the prevalence of current
      smoking, obesity, physical inactivity, low income, diabetes and hypertension.
      Combining smoking prevalence data from the 2000/01 CCHS, mortality data from the
      1995 to 1997 Canadian Mortality Database, and relative risk estimates (relating
      smoking and smoking-associated deaths) from the American Cancer Society's Cancer
      Prevention Study II, SAM values were generated using population-attributable risk
      techniques. RESULTS: Based on self-reported data, the 2000/01 CCHS shows that
      26.0% of Canadians currently smoke, 14.9% are obese, 53.5% are physically
      inactive, 11.3% have low income, 13.0% have hypertension and 4.2% have diabetes.
      Cardiovascular and all-cause SAM were estimated at 18,209 and 44,271 annual
      deaths, and contributed to 23% and 22% of total CVD and all-cause mortality in
      Canada, respectively. There are large variations in the prevalence of CVD risk
      factors and in SAM estimates between sexes and across age groups and geographic
      regions. CONCLUSIONS: The high prevalence of potentially modifiable CVD risk
      factors and the large variation that exists between subgroups of the Canadian
      population suggest that the burden of CVD could be reduced through risk factor
      modification. While prevalence data for risk factors in a population give an
      initial understanding of some of the contributing causes of a disease, the actual
      burden of disease caused by a risk factor is also modified by the magnitude of
      the increased risk to mortality and morbidity, and is best represented by its
      estimated attributable mortality and morbidity.

PMID- 14571311
TI  - Off-pump coronary artery bypass: the Sudbury experience.
AB  - OBJECTIVE: To examine factors relating to outcomes with off-pump coronary artery
      bypass (OPCAB) and to assess methods to improve the effectiveness of this
      approach SETTING: A small northern Ontario community hospital where surgical
      assistance, nursing familiarity with OPCAB and even anesthesiologist comfort
      varied DESIGN: Prospective collection of data with incremental audit of results
      and retrospective analysis of events METHODS: One hundred twenty-four consecutive
      patients, operated on by the same surgeon between April 1996 and June 2002, were
      selected on the basis of coronary anatomy. Progressively more complex multivessel
      revascularization, including that to the posterior wall, was undertaken over the
      course of the study period. Every attempt was made not to compromise use of
      arterial conduits, quality of anastomoses or completeness of revascularization.
      This represents the 'learning curve' of this study. MAIN RESULTS: Approximately
      6% of patients developed a hemodynamic crisis requiring acute on-pump conversion.
      This tended to occur in patients undergoing complex multivessel OPCAB surgery and
      was associated with subsequent increased blood transfusion rate, operative time
      and mortality (2.8%), and poorer angiographic graft patency. This has led to a
      more cautious strategy including making the decision to proceed with OPCAB only
      after intraoperative assessment. CONCLUSION: 'Simple' OPCAB on easily accessible
      coronary arteries resulted in excellent early outcomes. Complex multivessel OPCAB
      for triple vessel disease involving difficult to access arteries was more
      demanding with higher perioperative complications and less effectiveness. Early
      enthusiasm for complex multivessel surgery has been gradually replaced with a
      more conservative use of OPCAB with improved intraoperative procedures, both of
      which have led to more favourable outcomes.

PMID- 14571312
TI  - Clinical review of radiofrequency catheter ablation for cardiac arrhythmias.
AB  - Clinical tachycardias are a major cause of morbidity with detrimental effects on
      quality of life, physical activity and health care costs. Catheter ablation
      delivered by radiofrequency energy (RFA) has gradually expanded as a therapeutic
      modality for cure or palliation and is being adapted to address the most
      difficult to treat tachycardias. The purpose of this paper is to inform decision
      makers about the current evidence base of RFA through a comprehensive literature
      review. Of the 968 citations identified through the literature search strategy,
      111 studies (11%) met the inclusion criteria. Only 10 of these studies (9%) were
      randomized, controlled trials. RFA of paroxysmal supraventricular tachycardia,
      atrial flutter and focal atrial tachycardias are all procedures associated with
      high procedural success rates and sustained clinical improvement within two years
      of follow-up. Limited evidence also demonstrates that elimination of these
      tachycardias improves symptoms and quality of life. RFAs of atrial fibrillation
      and ventricular tachycardia secondary to underlying structural heart disease are
      currently considered experimental procedures because there remains insufficient
      published data to draw conclusions about their clinical efficacy and safety
      profile. For all of the ablation procedures, there is a paucity of high-quality
      outcome studies comparing ablation with alternative therapeutic approaches and
      this provides the opportunity for future research.

PMID- 14571313
TI  - Review of economic evaluations of radiofrequency catheter ablation for cardiac
      arrhythmias.
AB  - A systematic review of current studies on the cost effectiveness of catheter
      ablation for treatment of tachycardia in adults was undertaken. The results are
      summarized based on a predefined framework of principles for economic evaluation.
      Of 192 abstracts identified, only three cost effectiveness studies were
      identified. Each focused on a different and specific patient group with selected
      target disorders, and used decision analysis modelling to estimate cost
      effectiveness. Radiofrequency catheter ablation is likely to be economically
      attractive compared with drug therapy in adult patients with frequently
      symptomatic paroxysmal supraventricular tachycardia (radiofrequency catheter
      ablation dominates drug therapy options) or in ventricular tachycardia patients
      with pre-existing ischemic coronary disease (cost effectiveness ratio of about US
      $21,000 per quality adjusted life year), but not in the treatment of asymptomatic
      Wolff-Parkinson-White syndrome patients. However, these studies evaluated
      different types of tachycardias in differing patient populations and all are
      based on United States data, so decision-makers must be cautious when applying
      these results to a general population with tachycardia in the Canadian context.

PMID- 14571314
TI  - [Prevention, screening and therapy of thyroid diseases and their cost
      effectiveness].
AB  - Cost-effectiveness analyses focused on benign thyroid diseases are under
      represented in the literature. The calculation of costs per additionally gained
      life year is difficult: The benefit of prevention is shifted into the distant
      future. The influence of an untreated subclinical thyroid disease on life
      expectancy can only be demonstrated by a long-term follow-up and by
      epidemiological databases. Iodine supplementation and programs for the prevention
      of tobacco smoking (primary prevention) are very cost-effective. Smoking
      increases the risk both of multinodular goiter and of Graves' disease. Screening
      programs (secondary prevention) are discussed for the laboratory parameters
      thyrotropin (TSH), calcium and calcitonin. TSH testing seems to be very cost
      effective for epidemiological considerations in a certain lifespan (newborn,
      pregnancy, postpartal, older persons, hospitalisation due to acute diseases) and
      in persons with previously elevated TPO-antibodies or TSH-values >2 mU/l, but
      dedicated cost-effectiveness analyses are lacking. On the other hand, the cost
      effectiveness of a routine TSH testing beyond the age of 35 years has been shown
      by a high-quality decision analysis. Therapeutic strategies (tertiary prevention)
      aim at the avoidance of complications (atrial fibrillation, myocardial
      infarction, death for cardiac reasons) and of iatrogenic complications. Examples
      of a tertiary prevention are: firstly the definitive therapy of Graves' disease
      in patients who have an increased risk of relapse after antithyroid drugs (ATD),
      secondly the radioiodine therapy for subclinical hyperthyroidism and the
      radioiodine therapy of large goiters in older patients or in patients suffering
      from a relevant comorbidity. Cost-effectiveness analyses for different
      therapeutic strategies of Graves' disease were published using a lifelong time
      horizon. The ablative radioiodine dose-regime is cost-effective as a first line
      therapy if the risk of relapse after ATD exceeds 60%.

PMID- 14571315
TI  - Use of statistical parametric mapping of (18) F-FDG-PET in frontal lobe epilepsy.
AB  - AIM: Evaluation of the use of statistical parametrical mapping (SPM) of FDG-PET
      for seizure lateralization in frontal lobe epilepsy. PATIENTS: 38 patients with
      suspected frontal lobe epilepsy supported by clinical findings and video-EEG
      monitoring. METHOD: Statistical parametrical maps were generated by subtraction
      of individual scans from a control group, formed by 16 patients with negative
      neurological/psychiatric history and no abnormalities in the MR scan. The scans
      were also analyzed visually as well as semiquantitatively by manually drawn ROIs.
      RESULTS: SPM showed a better accordance to the results of surface EEG monitoring
      compared with visual scan analysis and ROI quantification. In comparison with
      intracranial EEG recordings, the best performance was achieved by combining the
      ROI based quantification with SPM analysis. CONCLUSION: These findings suggest
      that SPM analysis of FDG-PET data could be a useful as complementary tool in the
      evaluation of seizure focus lateralization in patients with supposed frontal lobe
      epilepsy.

PMID- 14571316
TI  - [Neurocognition and PET. Strategies for data analysis in activation studies on
      working memory].
AB  - AIM: In cognitive neuroscience regional cerebral blood flow (rCBF) imaging with
      positron-emission-tomography (PET) is a powerful tool to characterize different
      aspects of cognitive processes by using different data analysis approaches. By
      use of an n-back verbal working memory task (varied from 0- to 3-back) we present
      cognitive subtraction analysis as basic strategy as well as parametric and
      covariance analyses and discuss the results. METHODS: Correlation analyses were
      performed using the individual performance rate as an external covariate,
      computing inter-regional correlations, and as network analysis applying
      structural equation modelling to evaluate the effective connectivity between the
      involved brain regions. RESULTS: Subtraction analyses revealed a fronto-parietal
      neuronal network also including the anterior cingulate cortex and the cerebellum.
      With higher memory load the parametric analysis evidenced linear rCBF increases
      in prefrontal, pre-motor and inferior parietal areas including the precuneus as
      well as in the anterior cingulate cortex. The rCBF correlation with the
      individual performance as external covariate depicted negative correlations in
      bilateral prefrontal and inferior parietal regions, in the precuneus and the
      anterior cingulate cortex. The network analysis demonstrated mainly occipito
      frontally directed interactions which were predominantly left-hemispheric.
      Additionally, strong linkages were found between extrastriate and parietal
      regions as well as within the parietal cortex. CONCLUSION: The data analysis
      approaches presented here contribute to an extended and more elaborated
      understanding of cognitive processes and their different sub-aspects.

PMID- 14571317
TI  - 18F-FDG PET: early postoperative period of oro-maxillo-facial flaps.
AB  - AIM: We addressed the feasibility of FDG-PET to differentiate between viability
      and non-viability in the immediate postoperative assessment of flaps (autologous
      microvascular anastomosed pedicled flaps) in oro-maxillo-facial surgery. METHODS:
      3-7 days after surgery, FDG-PET was done in 38 patients who had received flaps
      for re-construction of the mandible after partial resection. The studies were
      done on a dedicated full ring PET-scanner (ECAT EXACT HR+, Siemens/CTI).
      Acquisition started between 60 and 80 min post injection. The findings of the
      soft tissue component of the flaps were grouped using a three point scale: (I) no
      defect, (II) small defects, (III) one large defect. The results of PET were
      compared with the clinical course for at least 3 months. RESULTS: "No defect" on
      the FDG-PET study identified vi-ability of the flap and predicted normal clinical
      follow-up (22/38 patients). "Small defects" visualized areas of decreased
      perfusion and decreased glucose metabolism indicating risk of non-viability
      (13/38 patients); adapt-ing the postsurgical management led to delayed but
      uncomplicated healing of the flaps in these patients. "One large defect"
      demonstrated early necrosis of the flap (3/38 patients). After removal and
      replacement of this necrotic portion of the flap the second FDG-PET scan of these
      3 patients demonstrated the uncomplicated post-operative healing. CONCLUSION: FDG
      PET facilitated the assessment of viability and non viability of flaps in the
      immediate postsurgical period, and demonstrated the usefulness of FDG-PET for
      postoperative care and prognosis.

PMID- 14571318
TI  - [Time consumption and quality of an automated fusion tool for SPECT and MRI
      images of the brain].
AB  - AIM: Although the fusion of images from different modalities may improve
      diagnostic accuracy, it is rarely used in clinical routine work due to logistic
      problems. Therefore we evaluated performance and time needed for fusing MRI and
      SPECT images using a semiautomated dedicated software. PATIENTS, MATERIAL AND
      METHOD: In 32 patients regional cerebral blood flow was measured using (99m)Tc
      ethylcystein dimer (ECD) and the three-headed SPECT camera MultiSPECT 3. MRI
      scans of the brain were performed using either a 0,2 T Open or a 1,5 T Sonata.
      Twelve of the MRI data sets were acquired using a 3D-T1w MPRAGE sequence, 20 with
      a 2D acquisition technique and different echo sequences. Image fusion was
      performed on a Syngo workstation using an entropy minimizing algorithm by an
      experienced user of the software. The fusion results were classified. We measured
      the time needed for the automated fusion procedure and in case of need that for
      manual realignment after automated, but insufficient fusion. RESULTS: The mean
      time of the automated fusion procedure was 123 s. It was for the 2D significantly
      shorter than for the 3D MRI datasets. For four of the 2D data sets and two of the
      3D data sets an optimal fit was reached using the automated approach. The
      remaining 26 data sets required manual correction. The sum of the time required
      for automated fusion and that needed for manual correction averaged 320 s (50-886
      s). CONCLUSION: The fusion of 3D MRI data sets lasted significantly longer than
      that of the 2D MRI data. The automated fusion tool delivered in 20% an optimal
      fit, in 80% manual correction was necessary. Nevertheless, each of the 32 SPECT
      data sets could be merged in less than 15 min with the corresponding MRI data,
      which seems acceptable for clinical routine use.

PMID- 14571319
TI  - Combined transmission and (99m)Tc-sestamibi emission tomography for localization
      of mediastinal parathyroid glands.
AB  - AIM: Although parathyroid scintigraphy using (99m) Tc-sestamibi is considered the
      best preoperative localization method for hyperfunctioning parathyroid tissue it
      lacks the anatomical details required for successful, minimal invasive surgery of
      ectopic parathyroid lesions. This study presents the role of combined SPECT/X-ray
      CT imaging in a single device for localization of mediastinal parathyroid glands.
      METHODS: (99m) Tc-sestamibi SPECT/X-ray-CT was performed by gamma camera-mounted
      anatomical X-ray tomography (GMAXT; GE Medical systems, Millenium VG with
      Hawkeye) in four patients with ectopic parathyroid glands (two patients with
      primary, two with persistent secondary hyperparathyroidism). The device contains
      an X-ray tube and a set of detectors that rotate around the patient combined with
      a gamma camera. For comparison with GMAXT addition-ally high resolution computed
      tomography images of the neck and mediastinum were performed. RESULTS: Correct
      preoperative localization was achieved. The parathyroid glands were located in
      the anterior mediastinum. High resolution computed tomography could not provide
      further details. Three patients were operated by a minimal invasive open and one
      patient by a transsternal approach because of concomitant aortic valve
      replacement. CONCLUSION: (99m)Tc-sestamibi/X-ray-CT fusion imaging in a single
      device can accurately localise ectopic or supernumerary mediastinal parathyroid
      tumours in primary and secondary hyperparathyroidism. Morbidity,radiation
      exposure, time, and costs are reduced by avoiding multiple diagnostic
      examinations and minimal invasive parathyroid surgery becomes possible.

PMID- 14571321
TI  - Chlamydia pneumoniae accelerates coronary artery disease progression in
      transgenic hyperlipidemia-genetic hypertension rat model.
AB  - Chlamydia pneumoniae (Cpn) has been associated with human coronary artery disease
      but causal relevance as a risk factor has not been shown. Several rabbit and
      mouse model studies demonstrate exacerbation of aortic atherosclerosis by Cpn,
      however impact of Cpn on coronary artery disease (CAD) and survival outcomes has
      not been shown. To study this, we used specific pathogen-free, inbred, transgenic
      CAD Dahl salt-sensitive (S) hypertensive (Tg53) rats and control inbred, non
      transgenic Dahl S (nonTg) rats to analyze the effects of Cpn infection on
      macrophage foam cell formation, coronary artery disease progression, and effect
      on survival. Cpn infection induced acceleration of foam cell formation in
      hyperlipidemic Tg53 recruited peritoneal macrophages. This effect is
      hyperlipidemia-dependent. The transcription profile of Tg53-Cpn macrophage foam
      cells is different from control mock-inoculated (Tg53-spg) and heat-inactivated
      (Tg53-iCpn) macrophages (ANOVA P < 0.0001). Decreased survival was detected in
      Tg53-Cpn compared with control nonTg-Cpn and mock-infected Tg53-mouse pneumonitic
      rats (P = 0.009) and was associated with "culprit" coronary plaques and left
      atrial thrombi. These data demonstrate that in the presence of significant
      hyperlipidemia and hypertension, one-time Cpn infection at 5 mo of age
      (associated with early CAD stage) accelerates progression to overt-CAD in the
      Tg53 rat model. The data support the hypothesis that untreated Cpn infection is a
      causal risk factor for CAD progression most likely mediated by Cpn-induced
      accelerated macrophage foam cell formation.

PMID- 14571320
TI  - The cholinergic anti-inflammatory pathway: a missing link in
      neuroimmunomodulation.
AB  - This review outlines the mechanisms underlying the interaction between the
      nervous and immune systems of the host in response to an immune challenge. The
      main focus is the cholinergic anti-inflammatory pathway, which we recently
      described as a novel function of the efferent vagus nerve. This pathway plays a
      critical role in controlling the inflammatory response through interaction with
      peripheral a7 subunit-containing nicotinic acetylcholine receptors expressed on
      macrophages. We describe the modulation of systemic and local inflammation by the
      cholinergic anti-inflammatory pathway and its function as an interface between
      the brain and the immune system. The clinical implications of this novel
      mechanism also are discussed.

PMID- 14571322
TI  - Absence of poly(ADP-ribose)polymerase-1 alters nuclear factor-kappa B activation
      and gene expression of apoptosis regulators after reperfusion injury.
AB  - Poly(ADP-ribose) polymerase-1 (PARP-1) is activated in response to DNA injury in
      eukaryotic cells and has been implicated in cell dysfunction in reperfusion
      injury. In this study we investigated the role of PARP-1 on apoptosis in early
      myocardial reperfusion injury. Mice genetically deficient of PARP-1 (PARP-1-/-)
      and wild-type littermates were subjected to myocardial ischemia and reperfusion.
      Myocardial injury was assessed by measuring the serum levels of creatine
      phosphokinase and oligonucleosomal DNA fragments in the infarcted area.
      Expression of the anti-apoptotic protein, Bcl-2, and the pro-apoptotic protein,
      Bax, was analyzed by Western blot. Activation of caspases, important executioners
      of apoptosis, and activation of the nuclear factor kappa B (NF-kappa B) pathway
      were evaluated. Gene expression profiles for apoptotic regulators between PARP-1
      /- and wild-type mice also were compared. Myocardial damage in PARP-1-/- mice was
      reduced significantly, as indicated by lower serum creatine phosphokinase levels
      and reduction of apoptosis, as compared with wild-type mice. Western blot
      analyses showed increased expression of Bcl-2, which was associated with
      reduction of caspase-1 and caspase-3 activation. This cardioprotection was
      associated with significant reduction of the activation of I kappa B kinase
      complex and NF-kappa B DNA binding. Microarray analysis demonstrated that the
      expression of 29 known genes of apoptotic regulators was significantly altered in
      PARP-1-/- mice compared with wild-type mice, whereas 6 known genes were similarly
      expressed in both genotypes. The data indicate that during reperfusion absence of
      PARP-1 leads to reduction of myocardial apoptosis, which is associated with
      reduced NF-kappa B activation and altered gene expression profiles.

PMID- 14571323
TI  - Derepression of HMGA2 gene expression in retinoblastoma is associated with cell
      proliferation.
AB  - To assess whether retinoblastoma formation is associated with the expression of
      high mobility group (HMG) A2 protein, a transcription factor that is highly
      expressed during embryogenesis and completely repressed in normal adult tissues,
      we performed Northern and Western blots and RT-PCR analyses, and
      immunohistochemistry to test for HMGA2 expression. We used established
      retinoblastoma cell lines in tumors grown in nude mice and clinical
      retinoblastoma specimens, and contrasted these tumors with normal embryonic and
      adult retina. Adenoviral-mediated antisense experiments were conducted on the
      retinoblastoma cell lines to suppress HMGA2 expression and determine if cell
      proliferation is HMGA2-dependent. We also transfected a retinoblastoma cell line
      to identify cis-regulatory elements and transcription initiation sites on the
      HMGA2 gene promoter. HMGA2 gene expression was silenced in terminally
      differentiated retina of 6-wk-old mice, but it was detected in retina of a 13.5-d
      postcoitum embryo. Reactivation of HMGA2 gene expression was observed in the
      retinoblastoma cell lines Y79, WERI-Rb1, and TOTL-1, in tumors derived from some
      of these cells propagated in nude mice, and in a high frequency of
      retinoblastomas excised from human patients. This suggests that expression of
      HMGA2 gene in retinoblastoma cells involves a derepression process. By using an
      antisense approach to block HMGA2 expression, we observed a decrease in the
      number of proliferating retinoblastoma cells. As a 1st step toward understanding
      HMGA2 gene reactivation in retinoblastoma, we mapped the 2 transcription
      initiation sites and associated positive regulatory elements within the WERI-Rb1
      cells. Our discovery of derepression of HMGA2 gene expression in retinoblastoma
      provides the 1st evidence that this protein might contribute to neoplastic
      transformation of retina cells.

PMID- 14571324
TI  - Diversification of the Ig variable region gene repertoire of synovial B
      lymphocytes by nucleotide insertion and deletion.
AB  - Although the changes that occur in Ig V region genes during a B lymphocyte's
      response to antigen usually result from point mutations, nucleotide insertion and
      deletion also alter gene sequence. We identified nucleotide insertions and
      deletions (3 to 12 bp) at a frequency of 1.34%, in Ig V gene cDNA from B
      lymphocytes residing in the synovial tissues of patients with rheumatoid
      arthritis. Because the added or lost nucleotides occurred in multiples of 3, they
      maintained the original reading frame and coded a potentially intact receptor.
      These V gene modifications were generated somatically, because they were
      identified in the original cDNA by HCDR3-specific polymerase chain reaction and
      were not found in other B cells using the same VH genes. Insertions and deletions
      were detected only in IgG+ and IgA+ transcripts, which exhibited 3 times more
      point mutations than IgM+ transcripts. In addition, they were usually found in
      the complementarity determining region, typical targets of somatic mutation. The
      occurrence of insertion/ deletion in isotype-switched cDNA with higher numbers of
      V gene mutations that localized to hot spots for V gene mutation suggests that
      these diversification events were related to the somatic hypermutation process.
      In support of this, an AGY hot spot motif and a short stretch of DNA similar in
      sequence to the inserted or deleted segments could be found next to the
      insertions/deletions, suggesting that these modifications arose from DNA
      duplication following DNA stand breaks. Thus, nucleotide insertion/deletion can
      lead to B-cell receptor diversification in B lymphocytes that clonally expand in
      synovial tissues of patients with rheumatoid arthritis.

PMID- 14571325
TI  - Zinc protoporphyrin IX binds heme crystals to inhibit the process of
      crystallization in Plasmodium falciparum.
AB  - The intraerythrocytic Plasmodium falciparum parasite converts most of host
      hemoglobin heme into a nontoxic heme crystal. Erythrocyte zinc protoporphyrin IX,
      normally present at 0.5 microM, which is a ratio of 1:40,000 hemes, can elevate
      10-fold in some of the anemias associated with malaria disease protection. This
      work examines a binding mechanism for zinc protoporphyrin IX inhibition of heme
      crystallization similar to the antimalarial quinolines. Zinc protoporphyrin IX
      neither forms crystals alone nor extends on preformed heme crystals. Inhibition
      of both seed heme crystal formation and crystal extension occurs with an
      inhibitory concentration (IC)50 of 5 microM. Field emission in-lens scanning
      electron microscopy depicts the transition and inhibition of heme monomer
      aggregates to heme crystals with and without seeding of preformed hemozoin
      templates. In vitro zinc protoporphyrin IX, like the quinolines, binds to heme
      crystals in a saturable, specific, pH, and time-dependent manner. The ratio at
      saturation is approximately 1 zinc protoporphyrin IX per 250 hemes of the
      crystal. Unlike the quinolines, zinc protoporphyrin IX binds measurably in the
      absence of heme. Isolated ring and trophozoite stage parasites have an elevated
      zinc protoporphyrin IX to heme ratio 6 to 10 times that in the erythrocyte
      cytosol, which also corresponds to elevated ratios found in heme crystals
      purified from Plasmodium parasites. This work implicates protection from malaria
      by a mechanism where elevated zinc protoporphyrin IX in anemic erythrocytes binds
      to heme crystals to inhibit further crystallization. In endemic malaria areas,
      severe iron deficiency anemia should be treated with antimalarials along with
      iron replenishment.

PMID- 14571326
TI  - Effect of citric acid and citric acid-sucrose mixtures on swallowing in
      neurogenic oropharyngeal dysphagia.
AB  - The ability of sour and sweet-sour mixtures to improve swallowing in 11 nursing
      home residents with neurogenic oropharyngeal dysphagia was investigated using
      fiberoptic endoscopic evaluation of swallowing. Citric acid (2.7%) significantly
      reduced aspiration and penetration compared with water. Teaspoon delivery of
      liquids significantly reduced aspiration and penetration compared with natural
      cup drinking. Subjects tended to appropriately self-regulate the cup volume they
      consumed after the first trial. A significant increase in spontaneous dry
      swallows was observed after both taste stimuli. The mechanisms for improved
      swallowing due to citric acid are not understood but may be due to increased
      gustatory and trigeminal stimulation of acid to the brainstem in neurologically
      impaired subjects.

PMID- 14571327
TI  - Pharyngoesophageal manometry with an original balloon sensor probe for the study
      of oropharyngeal dysphagia.
AB  - The goal of our study was to verify the clinical applicability of an original
      balloon sensor probe for the manofluorographic study of oropharyngeal dysphagia.
      A prototype apparatus for manofluorography was developed and a standard perfused
      probe for esophageal manometry was modified by applying fluid-filled floppy
      balloons 0.5-, 1-, and 2.5-cm long. A group of healthy volunteers and a group of
      patients affected by oropharyngeal dysphagia underwent manofluorography.
      Statistically significant differences were calculated between the groups with
      regard to the upper esophageal sphincter (UES) basal and postrelaxation
      contraction pressures (p<0.05, Student's t test, 2.5- vs. 1-cm-long balloon
      sensors). In the group of patients versus the group of healthy volunteers,
      statistically significant differences were calculated with regard to pharyngeal
      intrabolus pressure, UES residual and UES postrelaxation contraction pressures,
      and mean diameter of the UES during maximal opening (p<0.05, Student's t test). A
      strong negative correlation (r=-0.92, p=0.001; r=-0.93, p=0.006 linear regression
      analysis) was observed between intrabolus pressure and UES diameter during
      maximum opening in the group of patients. The balloon probe demonstrated its
      reliability and clinical adequacy for the study of swallowing disorders.

PMID- 14571328
TI  - Balloon sensors for the manometric recording of the pharyngoesophageal tract: an
      experimental study.
AB  - The goal of our study was to investigate manometric balloon sensors of original
      conception in order to overcome the limitations of perfused and solid-state
      sensors in the assessment of the pharyngoesophageal motility abnormalities. A
      standard perfused probe for esophageal manometry was modified by applying fluid
      filled floppy balloons 0.5-, 1-, and 2.5-cm long. The balloon sensor probe was
      tested at the bench with regard to the response to the applied pressures, the
      frequency-response curve, and the behavior during propagation of the peristaltic
      waves in an esophageal model. The physical properties of the balloon sensors
      proved to be adequate for pharyngoesophageal motility studies. The static
      response of the balloon probe to the applied pressures was linear. For the
      frequency-response curve, the upper cutoff frequency (A=1/square root of 2) was
      23 Hz, resonance frequency was 16 Hz, and resonance amplification was 1.6. No
      statistically significant differences were observed between balloon sensors of
      different length with regard to amplitude and duration of recorded peristaltic
      waves (p>0.05). In conclusion, the balloon probe has the physical and technical
      characteristics required for the study of swallowing disorders.

PMID- 14571329
TI  - Morphologic parameters of normal swallowing events using single-shot fast spin
      echo dynamic MRI.
AB  - This study was designed to determine visible and measurable morphological
      parameters in normal swallowing using dynamic MRI with single-shot fast spin echo
      (SSFSE), as a preliminary study in view of noninvasive MRI swallowing evaluation
      in patients with dysphagia. Seven healthy volunteers aged 24-40 underwent dynamic
      MRI with SSFSE, with a 1.5-T unit, using a head and neck antenna. Patients
      repeated dry swallow, water swallow, marshmallow swallow, cake swallow, and
      cookie chewing for a total of five series, with 15 acquisitions per series at a
      rate of 700 ms per acquisition. A checklist of swallowing events and anatomic
      landmarks was used to determine which anatomic landmarks are always visible,
      which phases or swallowing movements are always visible, and which landmarks can
      be used to measure oral and pharyngeal motion in swallowing. The oral
      preparatory, oral, and oropharyngeal phases of deglutition were visible in all
      cases. No aspiration, reflux, or abnormal residue was observed. Spatial
      resolution allowed for anatomical measurements of laryngeal elevation,
      oropharyngeal diameter, and tongue base and velum displacement in all cases.
      SSFSE dynamic MRI is pertinent for evaluation of the anatomical and physiological
      characteristics of swallow. The temporal parameters, however, cannot be studied
      using this technique. Motion artifacts preclude its use in the study of
      mastication. It remains complementary to videofluoroscopy and other techniques in
      swallow evaluation.

PMID- 14571330
TI  - Isolated proximal esophageal injury from blunt trauma: endoscopic stricture
      dilatation.
AB  - Blunt neck trauma can cause isolated esophageal injuries that may be difficult to
      recognize. A high index of suspicion is necessary for optimal identification and
      management of this condition. We report a case of blunt esophageal trauma
      resulting from a motor vehicle accident that was initially unrecognized until the
      patient developed a tight stricture of the cervical esophagus. This was
      successfully dilated endoscopically. Aerodigestive trauma resulting from neck
      injuries is reviewed with emphasis on the pathophysiology of esophageal trauma.

PMID- 14571331
TI  - Problems with eating and drinking in patients with unilateral peripheral facial
      paralysis.
AB  - Patients with facial paralysis not only suffer from asymmetry of the face, but
      also from problems with eating and drinking. To demonstrate that these patients
      have many problems with activities such as eating and drinking, we examined 17
      outpatients with a unilateral peripheral facial paralysis for the presence of
      problems in these functions. To collect data, all patients completed a
      questionnaire concerning the problems they had directly following onset of the
      paralysis and at the moment of this study. In addition, they were examined to
      determine the severity of the paralysis, the problems with eating and drinking,
      their experiences regarding impairments and disabilities, and the compensatory
      behavior. The result of the study is a portrayal of problems and conscious or
      unconscious compensations. Furthermore, we concluded that the Sunnybrook Facial
      Grading System score does not predict the number of problems in eating and
      drinking, the number of compensations, and the emotional impact. Significant
      correlations are found only between various scores on Visual Analog Scales and
      the number of compensatory actions. Patients differ in how they experience the
      extensive problems due to the facial paralysis and in the extent to which they
      are successful in adaptation. Consulting a speech therapist for treatment of
      functional problems is a meaningful adjunct to regular therapy. The treatment of
      deglutition disorders can be best based upon the detailed information of the
      questionnaire and the examination of eating, drinking, and compensatory behavior.

PMID- 14571332
TI  - Dysphagia associated with risperidone therapy.
AB  - Dysphagia is occasionally reported in patients taking neuroleptic agents,
      although the newer, "atypical" neuroleptics are generally believed to be
      associated with fewer neurologic side effects. We report a 76-year-old man who
      developed radiographically confirmed dysphagia when treated with risperidone; the
      dysphagia resolved when risperidone was withdrawn. Clinicians should be aware of
      the potential for this dangerous but highly reversible problem.

PMID- 14571333
TI  - Laryngeal paralysis: distinguishing Xth nerve from recurrent nerve paralysis
      through videoendoscopic swallowing study (VESS).
AB  - Distinction between unilateral recurrent laryngeal nerve paralysis and Xth nerve
      paralysis is a rarely addressed issue in the literature. However, it may be
      crucial to examine the cause of the paralysis and to perform the appropriate
      investigation. The videoendoscopic swallowing study has been demonstrated to be a
      useful tool in assessing pharyngeal function. Since in unilateral Xth nerve
      paralysis the pharynx is impaired on the same side as the vocal fold immobility,
      it may be easily detected by videoendoscopic swallowing study. The rotation of
      the posterolateral pharyngeal wall toward the opposite side during swallowing is
      a sign of impaired motor pharyngeal branches. To demonstrate the usefulness of
      the videoendoscopic swallowing study in distinguishing unilateral Xth nerve from
      isolated recurrent nerve paralysis, a series of six patients were studied
      prospectively. Diagnosis of Xth nerve paralysis focused the investigation toward
      the high neck or the skull base area. Paralysis of the Xth nerve was suspected in
      all cases and diagnosis was achieved in five cases by the workup performed.
      Videoendoscopic swallowing study is a cost-effective and easily available tool
      which should be performed in all cases of vocal fold paralysis.

PMID- 14571334
TI  - Effects of cuff deflation and one-way tracheostomy speaking valve placement on
      swallow physiology.
AB  - This study examined the effects of tracheostomy cuff deflation and one-way
      speaking valve placement on swallow physiology. Fourteen nonventilator-dependent
      patients completed videofluoroscopic swallow studies (VFSS) under three
      conditions: (1) cuff inflated, (2) cuff deflated, and (3) one-way valve in place.
      Four additional patients with cuffless tracheostomy tubes completed VFSS with and
      without the one-way valve in place. All swallows were analyzed for the severity
      of penetration/aspiration using an 8-point penetration-aspiration scale. Seven
      preselected swallow duration measures, extent of hyolaryngeal elevation and
      anterior excursion, and oropharyngeal residue were also determined. Scores on the
      penetration-aspiration scale were not significantly affected by cuff status,
      i.e., inflation or deflation. However, one-way valve placement significantly
      reduced scores on the penetration-aspiration scale for the liquid bolus. Patients
      who are unable to tolerate thin liquids may be able to safely take thin liquids
      when the valve is in place. However, one-way valve placement may not be
      beneficial for all patients. Clinicians who complete VFSS with tracheostomized
      patients should include several bolus presentations with a one-way speaking valve
      in place before making any decisions regarding the use of the valve as a means to
      reduce aspiration.

PMID- 14571335
TI  - Swallowing apnea as a function of airway closure.
AB  - The purpose of this research was to ascertain whether the existence of swallowing
      apnea (SA) was the sole result of glottic closure or the result of its own neural
      mechanism. Forty individuals served as participants. Groups 1 and 2 consisted of
      10 individuals with laryngectomy less than one year and 10 individuals greater
      than one year, respectively. Groups 3 and 4 comprised 20 individuals who were age
      and gender-matched to Groups 1 and 2. SA duration (SAD) was acquired during
      saliva swallows and 10-, 15-, 20-, and 25-ml water boluses. A repeated measures
      ANOVA was performed to determine mean differences in SAD as a function of group
      and bolus volume. Significant main effects of group and bolus volume were found
      and a significant interaction of group x bolus volume was found. In post-hoc
      analyses, both groups with laryngectomy exhibited statistically longer SADs than
      control groups. In single-df comparisons, the laryngectomy group over one year
      exhibited significantly shorter SADs on smaller versus larger bolus volumes. Even
      though SA is theoretically no longer needed in individuals with laryngectomy, the
      presence of SA remained in both groups with laryngectomy. Thus, these results
      support the hypothesis that SA is the result of its own neural command.

PMID- 14571336
TI  - The evaluation of dysphagia after anterior cervical spine surgery: a case report.
AB  - The anterior approach to cervical spine surgery is associated with many possible
      complications. Dysphagia has commonly been reported as one of these
      complications. A closer examination of the reports of dysphagia following
      anterior cervical spine surgery, however, reveals that while new onset transient
      dysphagia is often mentioned, long-term (greater than 48 hours) dysphagia has not
      been well described. In this article, we report the case of a 29-year-old female
      with long-term recurrent dysphagia following cervical spine surgery using the
      anterior approach. The important point about this case is that our patient's
      symptoms suddenly recurred for the first time after nearly a two-month period of
      normal swallowing. Consequently, this patient has required multiple dilations. As
      a result, despite an initial lack of swallowing dysfunction or the return of
      normal swallowing, clinicians should be aware of the importance of reassessing
      swallowing in patients who have undergone cervical spine surgery using the
      anterior approach.

PMID- 14571337
TI  - Arterial revascularization--advantages and pitfalls.
AB  - Arterial revascularization is still subject to debate, even though numerous
      publications have reported presumed advantages of arterial over venous grafts.
      This brief review summarizes current knowledge on arterial revascularization on a
      practical basis.

PMID- 14571338
TI  - Internal thoracic artery vs. vein grafts--postoperative angiographic findings in
      symptomatic patients after 1000 days.
AB  - BACKGROUND: Superior patency-rate of ITA, especially BITA-grafting to saphenous
      vein grafts, is conclusive. This study evaluates angiographic findings
      postoperatively in 663 symptomatic patients receiving one or both ITAs and vein
      grafts. METHODS: 663 patients (553 male, mean age 62) with CABG operated between
      1/94 and 6/02 underwent reangiography due to reappearance of angina or unclear
      cardiac symptoms. Angiographic data were compared for patency rate of single ITA
      (n = 379), bilateral ITA (n = 220) or vein grafts. Recatherization was performed
      after an average of 1000 days (+/- 766 days). Severe bypass stenosis or occlusion
      was related to target vessels for all grafts. RESULTS: 2099 Bypasses were
      performed in 663 patients. Severe stenosis or occlusion was detected in 255 ACB
      (19.9 %) of 1280 and 93 ITAs of 819 (11.4 %, p < 0.001). Patency was 88.8 % (532)
      for LITA, 88.2 % (194) for RITA. Target vessels were as follows: LITA: 60 % (358)
      LAD, 23.5 % (141) CX, RITA: 82 % (180) LAD. Occlusion rate for LITA was as
      follows: to LAD 7 %, to DIA 8.7 %, to CX 8.5 %. Occlusion rate for RITA as
      follows: to LAD 6.7 %, to DIA 16.7 %, to CX 0, to RCA 14.3 %. Occlusion rate for
      ACB was as follows: to LAD 18.7 %, to DIA 12.6 %, to CX 14.1 %, to RCA 16.1 %.
      Despite symptoms, bypass patency was observed in 412 (62.1 %) of 663 patients.
      CONCLUSIONS: Superior patency of ITA, especially BITA grafting could be
      documented angiographically in a negative selected symptomatic population. Graft
      occlusion was nearly two fold higher in vein grafts. Our surgical strategy,
      revascularizising RITA with LAD, LITA with circumflex artery results in
      satisfactory mid-term graft patency.

PMID- 14571339
TI  - Morphology and density of initial lymphatics in human myocardium determined by
      immunohistochemistry.
AB  - BACKGROUND: Myocardial edema is a common finding in congestive heart failure,
      transplant rejection, and cardiomyopathy. Although pathological alterations in
      the lymphatic morphology are part of the underlying disease, knowledge on these
      changes is limited. However, lymphatic morphology may be investigated by
      immunohistochemical staining for fms-like tyrosine 4 kinase (flt-4), which is
      specific for lymphatic endothelium in adult tissue. METHODS: We used myocardial
      tissue of ventricular out flow tract taken from five human semilunar valves
      harvested as allografts but unsuitable for implantation for analysis, performing
      immunohistochemical staining for flt-4 with a commercially available antibody.
      Lymphatic morphometry was completed according Gundersen method. RESULTS:
      Immunohistochemical staining for flt-4 resulted in successful labeling of lymph
      capillaries in adult human myocardium. Lymph capillary density was calculated as
      50.7 +/- 12.5 per mm2 and average diameter was 3.7 +/- 0.7 microm. Conclusions.
      Lymph capillary morphology in human myocardium may be successfully determined by
      immunohistochemical staining for flt-4. Tissue samples as small as myocardial
      biopsies may be used for analysis. Using this method, morphological changes in
      myocardial lymphatics may be investigated in various cardiovascular diseases.

PMID- 14571340
TI  - Leukocyte-depleted secondary blood cardioplegia attenuates reperfusion injury
      after myocardial ischemia.
AB  - BACKGROUND: Activated neutrophils have been implicated in reperfusion injury of
      the myocardium; leukocyte depletion at the time of reperfusion may contribute to
      better myocardial protection after cardiac surgery. In the present study, we
      examined whether leukocyte depletion as an adjunct to terminal blood cardioplegia
      attenuates reperfusion injury. METHODS: Porcine hearts that had undergone 60
      minutes of normothermic ischemia with cardioplegia and 60 minutes of reperfusion
      under cardiopulmonary bypass were divided into four groups according to the
      methods of 15 min of controlled initial reperfusion: whole blood reperfusion (n =
      6), leukocyte-depleted reperfusion (n = 6), secondary blood cardioplegia (n = 6)
      and leukocyte-depleted secondary blood cardioplegia (n = 6). At 60 min of
      reperfusion, hemodynamic recovery, release of malondialdehyde (MDA) as a marker
      for free oxygen radicals, CK-MB-isoenzyme from the coronary sinus, recovery of
      adenosine triphosphate, and myocardial water content were evaluated. RESULTS: The
      group with leukocyte-depleted secondary blood cardioplegia showed the best
      hemodynamic recovery (Emax and total dp/dt), lowest levels of MDA, CK-MB and
      myocardial water content, and highest adenosine triphosphate recovery.
      CONCLUSIONS: These results suggest that controlled reperfusion with leukocyte
      depleted secondary blood cardioplegia attenuated severe damage of the myocardium
      as compared to whole blood reperfusion.

PMID- 14571341
TI  - Microcirculation of the sternum following harvesting of the left internal mammary
      artery.
AB  - BACKGROUND: Internal thoracic arterial grafts (ITA) in coronary artery bypass
      surgery provide excellent long-term patency results. Due to the elevated
      incidence of sternal infections following pedicled ITA harvesting, blood supply
      to the sternum has gained the focus of attention. This study sought to evaluate
      real time parameters of sternal microcirculation prior and immediately after
      harvesting of the ITA by a novel laser Doppler flowmetry and remission
      spectroscopy system (Oxygen-To-See (O2C), LEA Medizintechnik, Giessen). METHODS:
      21 patients (16 males, age 63 + 4 years, mean NYHA 2.3 +/- 0.3) scheduled for
      coronary artery bypass grafting (CABG) were enrolled into the study. After median
      sternotomy, the probe was placed sequentially pre- and retrosternally for
      measurements of tissue oxygen saturation (sO2), hemoglobin concentration (rHb),
      superficial (2 mm) und deep (8 mm) blood flow. Measurements were performed and
      analyzed before and after surgical harvesting of the ITA with a pedicle. RESULTS:
      Baseline pre- and retrosternal tissue oxygen saturation (sO2) were 90 +/- 3 % and
      87 + 4 %, respectively (n. s.). After left ITA harvesting, presternal sO2
      remained unchanged (90 + 4 %, n. s.), whereas retrosternal sO2 decreased
      significantly (54 + 4 %, p < 0.001). Simultaneously, retrosternal post-capillary
      venous filling (rHb) increased significantly after ITA harvesting (86 +/- 2 vs.
      93 + 2, p < 0.05), whereas presternal rHb remained unchanged. Retrosternal
      superficial and deep blood flow also decreased significantly (75 +/- 5 vs. 41 +/-
      4, and 94 +/- 5 vs. 52 +/- 6) in contrast to comparable presternal blood flow
      before and after ITA harvesting. There were neither superficial nor deep sternal
      wound infections occurred in the studied patient population. CONCLUSIONS: The
      pedicled harvesting of ITA leads to a significant decrease of microcirculatory
      blood flow, retrosternal tissue oxygen saturation, and an increase in post
      capillary venous filling. Parameters of microcirculation in the presternal area
      after ITA harvesting remained unchanged compared to baseline values. Hence, the
      incidence of sternal infections after ITA harvesting in coronary surgery may well
      be explained by a significant decrease of sternal blood supply in the
      retrosternal area. Further prospective randomized studies are needed to elucidate
      the potential role of skeletonized ITA preparation in sternal microcirculation.

PMID- 14571342
TI  - Cost and quality of life in thoracic surgery--a health economic analysis in a
      German center.
AB  - BACKGROUND: A critical look at the effectiveness of medical procedures and
      therapies is important with the increasing limitations on resources in health
      care. METHOD: The costs for treatment and the quality of life according to the SF
      36 were analyzed in a retrospective health economic study on 65 patients who had
      undergone surgery for primary non-small-cell lung cancer. RESULTS: The mean cost
      for all patients was 7,169 euro per patient. 38.8 % resulted from surgery, 31.6 %
      were attached to the preoperative phase on the general ward, 11 % postoperatively
      to the general ward. Intensive care costs accounted for 18.7 %. The cost of each
      surgical procedure ranged from 4,634 euro for a pneumonectomy to 8,366 euro for a
      lobectomy with sleeve resection of the bronchus. The most expensive factors were
      staff, disposable materials, pathological investigations, and radiology services.
      There was no difference in these proportions with stage of tumor or the surgical
      procedures undertaken. Quality of life as assessed by the SF-36 questionnaire
      ranged from 31.82 (physical functioning) to 75.0 (social functioning) one year
      after the operation. These scores were lower than for those with other chronic
      diseases. On average, 4.62 quality-adjusted life years were achieved. The cost
      per QALY was 1,970 euro. The extent of resection and the tumor staging correlates
      significantly with the mean cost per QALY. CONCLUSION: Thoracic surgery is cost
      intensive. With increasing staging of the tumor, the cost for treatment increased
      as with increased operation complexity.

PMID- 14571343
TI  - Epicardial treatment of atrial fibrillation using cryoablation in an acute off
      pump sheep model.
AB  - BACKGROUND: The purpose of this study was to test the feasibility and
      effectiveness of cryoablation therapy (SurgiFrost trade mark CryoCath, Endocare
      Inc., Irvine, California, USA) for linear epicardial treatment of atrial
      fibrillation in an acute off-pump sheep model. METHODS: After thoracotomy, we
      performed epicardial cryoablation (2 min intervals at -160 degrees C) with pacing
      electrodes positioned at the left atrial appendage (LAA), the pulmonary veins
      (PVs), the right atrial appendage (RAA), and the vena cava cranialis (VCC) in 8
      sheep. Circular epicardial ablations were performed with online temperature
      measurement in the ascending aorta and in the esophagus. The sheep were
      sacrificed two hours after ablation procedure, and heart, lungs, and esophagus
      were retrieved for histological examination. Out of all 8 sheep, histo
      pathological analysis was performed on the RAA and VCC in 6 sheep and on the CAA
      and PV in all 8 sheep. RESULTS: Thin-walled structures such as PVs and VCC showed
      electrical isolation. No significant changes in temperature in the descending
      aorta and the esophagus were observed. There was evidence of extensive transmural
      alteration including vascular lesions, myocardial degeneration and necrosis as
      well as epi- and endocardial necrosis in the left atria in three of 8 cases, in
      the right atria in 5 of 6 cases, in the VCC in 6 of 6 cases, and in the PV in 5
      of 8 cases. Mild lesions of the muscular layer of the esophagus were found in 7
      of 8 cases. CONCLUSIONS: Epicardial cryoablation is not effective on thicker
      tissues like LAA and RAA due to the rewarming of the current blood flow. However,
      thin tissues like VCC and PV can be isolated. Further chronic studies are
      necessary to evaluate the potential for regeneration of adjacent structures.

PMID- 14571344
TI  - Successful lung transplantation following lung volume reduction surgery.
AB  - BACKGROUND: Lung volume reduction surgery (LVRS) is an accepted treatment
      modality for patients with advanced emphysema. Recently, successful lung
      transplantation (LTX) has been reported following LVRS. We assess the pulmonary
      functions in lung transplant recipients after LVRS. METHODS: 8 patients - 5 males
      and 3 women--aged 53-66 years with advanced emphysema underwent LVRS. Following
      clinical deterioration and decline of pulmonary function, patients underwent
      single LTX. Post transplantation follow-up included pulmonary function, 6 minute
      walk distance (6 MWD) and recording perioperative complications. RESULTS: Median
      forced expiratory in one second (FEV 1) before and after LVRS were 24 % with 31 %
      predicted, respectively. All but one showed improvement in lung function and 6
      MWD following LVRS. Median maximal 6 MWD before and after LVRS was 222 and 316
      meters, respectively. Median time from LVRS to LTX was 46 months (range 10-83).
      All patients survived and were discharged after LTX. Median FEV1 before and after
      LTX was 23 % with 57 % predicted, respectively. Median 6MWD before and after LTX
      was 240 and 462 meters, respectively. NYHA classes improved from 3-4 to 1-2 in 7
      surviving patients. At transplantation, bleeding due to pleural adhesions was
      observed in 4 patients; two required blood transfusions. One patient developed
      acute respiratory distress syndrome and one had unilateral vocal cord paralysis.
      At nine-month follow-up, 7 patients are doing remarkably well, while one patient
      died 6 months after LTX due to bronchiolitis obliterans syndrome (BOS).
      CONCLUSIONS: LVRS is a therapeutic option in patients with end-stage emphysema.
      When emphysema deteriorates, LTX can be successfully performed with significant
      improvement of quality of life without significant additional risk.

PMID- 14571345
TI  - Evaluation of lung volume reduction surgery (LVRS) based on long-term survival
      rate analysis.
AB  - OBJECTIVE: Lung volume reduction surgery (LVRS) is an effective therapy for some
      patients with end-stage emphysema. In most cases, functional improvement is
      maximized during the first 6 months after surgery and decreases steadily
      afterwards. This study was aimed at gaining further understanding of the optimal
      candidates for LVRS and survival rates. METHODS: 62 patients with LVRS were
      selected according to the inclusion criteria. Changes in lung function were
      evaluated by FEV1, VC, RV, TLC, DLCO, PaO2, and PaCO2, and survival rates were
      analyzed at 12, 24, 36, and 48 months. Patients with LVRS were divided into two
      groups--those surviving after 48 months and those not surviving after 48 months-
      and analyzed according to group. RESULTS: The overall survival rate at 2 years
      and 4 years was 81.0 % and 67 %, respectively, with LVRS. VC, FEV1, TLC, DLCO,
      PaO2, and PaCO2 were potential factors leading to mortality according to
      univariate analysis. Multivariate analysis demonstrated that DLCO was the only
      independent factor that could predict the post-LVRS prognosis; the other factors
      failed as independent factors. Preoperatively, the FEV1 percentage predicted gave
      a good index for post-LVRS survival. CONCLUSIONS: Patients with higher
      preoperative FEV1 values had higher survival rates. These favorable long-term
      survival rates might justify LVRS for treating selected patients with severe
      emphysema. Additionally, DLCO turned out to be the only predictive factor for
      high mortality risk 4 years after LVRS. DLCO may thus be a very important marker
      in surgical planning.

PMID- 14571346
TI  - Distant failure after treatment of postoperative locoregional recurrence of non
      small cell lung cancer.
AB  - BACKGROUND: The standard treatment for patients with locoregional recurrence of
      non-small cell lung cancer (NSCLC) after complete resection has not been
      established. The aim of this study was to evaluate clinicopathologic
      characteristics, type of locoregional recurrence, pattern of subsequent failure,
      and survival after the recurrence. METHODS: Of 743 patients undergoing pulmonary
      resection for NSCLC in the National Cancer Center Hospital between 1990 and 1995,
      we retrospectively reviewed the medical charts of the 43 patients (5.8 %) found
      to have locoregional recurrence without distant metastasis or pleural or
      pericardial involvement. RESULTS: The median time to locoregional recurrence was
      13.6 months (range: 1.6 - 85.8 months). The most frequent site of recurrence was
      the mediastinal nodes in 21 of 43 patients (49 %). 33 patients (77 %) received
      further treatment for the recurrence: thoracic irradiation in 26, surgery in two,
      systemic chemotherapy in two, and a combination of the above in 3 patients.
      Subsequent distant failure was detected in 26 (68 %) of the 38 patients
      assessable for the analysis of failure pattern: lung in 11, brain in 6, bone in
      5, and others in 13. The median interval from the recurrence to distant failure
      was 8.4 months (range: 1.7-56.4 months). The median survival time after diagnosis
      of the locoregional recurrence was 10.5 months (range: 0-74.0 months). A
      multivariate analysis showed that local therapy for the locoregional recurrence
      had no significant impact on postrecurrent survival or distant failure-free
      survival. CONCLUSIONS: Many patients with postoperative locoregional recurrence
      developed distant metastases early after the first recurrence. Systemic
      chemotherapy in addition to local therapy may be of benefit in this population.

PMID- 14571347
TI  - Minithoracotomy with simultaneous video-assisted thoracoscopic surgery vs. video
      assisted thoracoscopic surgery for spontaneous hemopneumothorax.
AB  - BACKGROUND: Spontaneous hemopneumothorax, a life-threatening and rare disorder
      and complication of primary spontaneous pneumothorax, is regarded as a surgical
      emergency. We have prospectively investigated the differences in safety and
      utility between minithoracotomy with simultaneous video-assisted thoracoscopic
      surgery (MT + VATS) and the video-assisted thoracoscopic surgery approach (VATS)
      in the treatment of spontaneous hemopneumothorax. METHODS: From Jan 1998 to May
      2002, 248 patients with primary spontaneous pneumothorax were treated in our
      hospital. Among these patients, 12 (4.8 %) spontaneous hemopneumothorax occurred,
      all in the first episode of spontaneous pneumothorax. After tube thoracostomy,
      the amount of blood drainage ranged from 500 to 1,500 ml. 8 patients were treated
      by MT + VATS and 4 by VATS. RESULTS: During surgery, the sources of hemorrhage
      were all from the torn aberrant vessels between the apical blebs and the parietal
      pleura. The duration of main surgical procedure (including removal of blood clot
      in pleural cavity, control of bleeding and blebectomy) was significantly shorter
      in MT + VATS than in VATS (p < 0.01, Mann-Whitney U). There were no differences
      between these two groups in postoperative chest tube drainage duration, average
      postoperative pain score or hospital stay. No relapses occurred in the succeeding
      6 months to 4 years. CONCLUSIONS: Spontaneous hemopneumothorax is usually treated
      as an urgent surgical condition. MT + VATS is an easy accessible and safe
      procedure that could be applied as an initial treatment method in the patient
      with spontaneous hemopneumothorax, especially in the treatment of the patients
      with active hemorrhage and massive blood clot in the thorax.

PMID- 14571348
TI  - Right ventricular dysfunction in patients with acute inferior MI: role of RV
      mechanical support.
AB  - Right ventricular dysfunction after myocardial infarction is associated with high
      morbidity and mortality. If optimal medical management is ineffective, early
      consideration should be given to right-sided temporary mechanical assistance.

PMID- 14571349
TI  - Explantation of the heart for resection of primary cardiac tumors can be avoided
      by partial ex situ heart surgery.

PMID- 14571350
TI  - Efficacy and safety of venlafaxine ER vs. amitriptyline ER in patients with major
      depression of moderate severity.
AB  - INTRODUCTION: A double-blind, randomized phase-III study was conducted with the
      aim to compare the efficacy and safety of venlafaxine ER (extended release) with
      that of amitriptyline ER in moderately depressed outpatients. METHODS: Patients
      with major depression of moderate severity, HAM-D (Hamilton Depression scale, 21
      items) score 20-26, were given a six-week double-blind treatment with venlafaxine
      ER and amitriptyline ER in a dosis of 75 mg each, which could be increased to 150
      mg, if necessary. Efficacy was assessed using HAM-D and CGI (clinical global
      impression) scores. Safety analysis was carried out using the HAM-D item 3 to
      assess suicidality, the d2 test to evaluate attention and drug screening for
      benzodiazepines. Adverse events were recorded at each visit. RESULTS: 160
      patients were randomized. There were 151 patients available for analysis in the
      intent-to-treat (ITT) population. The according-to-protocol (ATP) population
      consisted of 117 patients, with 60 patients in the venlafaxine ER group and 57 in
      the amitriptyline ER (extended release) group. The non-inferiority of venlafaxine
      ER compared to amitriptyline ER with reference to the primary efficacy parameter,
      the change of HAM-D total score, could be proven in both the ITT population and
      the ATP population. There were no significant differences between groups in the
      HAM-D response rates and the CGI scores of items 1 (severity) and 2
      (improvement). Venlafaxine ER showed a more favorable safety profile than
      amitriptyline ER: adverse drug reactions were less frequent under venlafaxine ER
      than under amitriptyline ER. Most of the discontinuations in the amitriptyline ER
      group were due to dry mouth. The d2 test showed greater improvement of
      performance under venlafaxine ER. DISCUSSION: In this study with patients treated
      for major depression of moderate severity, the non-inferiority of venlafaxine ER
      compared to amitriptyline ER with respect to the chosen efficacy parameter could
      be demonstrated. Venlafaxine ER showed a more favorable safety profile than
      amitriptyline ER.

PMID- 14571351
TI  - Effects of treatment with chromium picolinate on peripheral amino acid
      availability and brain monoamine function in the rat.
AB  - Elemental chromium (Cr) is an essential micronutrient. It is required for optimal
      insulin activity and normal carbohydrate and lipid metabolism. Tri-valent
      chromium (Cr3+) is recommended for the treatment of diabetes and obesity. There
      is evidence that Cr3+ may have antidepressant properties, possibly by enhancement
      of monoamine function through its ability to increase amino acid transport to the
      brain. The aim of the present study was to investigate further the possible
      effects of Cr3+ treatment on peripheral amino acid availability and brain
      monoamine function in the rat. We undertook three studies in rats. The first was
      a time-course study in which animals were administered single doses of 50 mg/kg
      of Cr3+ picolinate and the second a dose-response study in which animals were
      given either 20 or 50 mg/kg Cr3+ picolinate versus vehicle alone via the intra
      peritoneal route. In the third, animals were fed a diet containing Cr3+
      picolinate (100 mg/kg) or a similar control diet for two weeks and were then
      sacrificed. Blood was sampled and brains were removed for later analysis. Results
      from the Cr3+ time-course study defined an optimal time for sampling of two hours
      after dosing. Results from the second study showed dose-related responses to Cr3+
      treatment for a number of measured biochemical parameters including serum
      corticosterone. In the sub-chronic treatment study Cr3+ significantly increased
      serum free tryptophan (TRP), non-esterified free fatty acids (NEFFAs),
      corticosterone, together with brain TRP, serotonin (5-hydroxytryptamine, 5-HT),
      noradrenaline (NA) and pineal melatonin. From other studies in our laboratory we
      have shown that Cr3+ treatment can modify brain 5-HT function, perhaps by
      altering the sensitivity of central 5-HT2A receptors. The peripheral effect of
      Cr3+ picolinate treatments and their consequential central effect on increased
      serotonergic and noradrenergic function may suggest that Cr3+ could have some
      antidepressant-like actions. Future studies to confirm this are to be done.

PMID- 14571352
TI  - Acute effects of cholecystokinin tetrapeptide on brain stem auditory evoked
      potentials in healthy volunteers.
AB  - This study investigated the effects of continuous slow intravenous infusion of
      cholecystokinin tetrapeptide (CCK-4) on brain stem auditory evoked potentials
      (BSAEP) in healthy subjects. Twenty-four subjects, 15 females and 9 males, were
      assigned to infusion with either placebo or CCK-4 in a randomized, double-blind,
      parallel group design. BSAEPs, mood, physical symptoms, and vital signs were
      assessed once before infusion and at 10 min and 40 min after the onset of
      infusion. In the 16 subjects (N = 8, CCK-4; N = 8, placebo) CCK-4, compared to
      placebo, delayed peak I latency during early infusion, slowed the latencies of
      peaks III and V, and decreased the amplitude of peak III throughout the infusion.
      No significant treatment differences were observed with respect to symptoms,
      mood, or cardiovascular measures. These preliminary findings suggest that CCK-4
      may interfere with information processing in the brain stem auditory pathways and
      that prolonged intravenous CCK-4 administration may be a useful challenge
      paradigm for investigating CCK's modulatory role on brain stem mechanisms
      mediating anxiety and panic in humans.

PMID- 14571353
TI  - Off-label use of antipsychotics in the community pharmacy: the sex differences.
AB  - Antipsychotic drugs are generally registered for treating schizophrenia,
      psychosis, mania, and conditions of severe (locomotor) agitation. In common
      practice, however, they are prescribed in a wide range of different psychiatric
      disorders. We conducted a retrospective, exploratory study to examine off-label
      use of antipsychotics and possibly sex differences. We defined antipsychotic use
      as quasi-label when used in non-registered disorders that have psychosis as an
      inherent co-morbidity. When antipsychotics were prescribed in disorders that are
      generally not known with psychosis, we defined this as off-label use. In this
      study, we combined pharmacy records with data from general practitioners in order
      to evaluate the range of diagnoses for which antipsychotic drugs are used. We
      focused on sex differences in type of disorder and in prescribed dosages of
      antipsychotic drugs. Among 97 male and 95 female antipsychotic users, we could
      classify women significantly more often as on-label antipsychotic drug users
      compared with men. Most often, this occurred with typical antipsychotic drug
      treatment. While female patients used equal dosages for on-label and quasi-/off
      label indications, we found that male patients used significantly lower dosages
      in quasi-/off-label indications compared with on-label indications. We suggest
      elaborate future research on the characteristics of quasi- and off-label
      antipsychotic drug use in order to define effective and safe use of antipsychotic
      drugs among off-label indications.

PMID- 14571354
TI  - A CYP2D6 phenotype-genotype mismatch in Japanese psychiatric patients.
AB  - The aim of the present study was to seek a CYP2D6 genotypic-phenotypic
      discordance possibility in Japanese patients under psychotropic drug treatment
      where the CYP2D6 status and pharmacodynamic responses differ from those in
      Caucasian psychiatric patients. Ninety drug-free, healthy volunteers and 14
      patients undergoing psychotropic drug treatment were phenotyped for their
      individual CYP2D6 activity using dextromethorphan as a probe, and then the
      metabolic ratio (MR) was calculated. For the genotyping, eight mutant alleles of
      the CYP2D6 genes were identified. Serum concentrations of two frequently co
      medicated psychotropic drugs, biperiden and levomepromazine, were determined by
      GC/MS. Genotyping revealed no poor metabolizers (PMs) enrolled in our study.
      Healthy volunteers exhibited an identical phenotype-genotype concordance, whereas
      7 of the 14 patients had significantly high (p < 0.05) MRs compared with genotype
      matched volunteers. Three of the patients who had the extensive metabolizer (EM)
      genotype had extremely high MRs and were classified as phenotypic PMs. Five
      patients plus all of the seven high MR patients were treated with levomepromazine
      and/or biperiden, respectively. Their mean serum steady-state concentrations were
      27.4 and 7.6 ng/ml, respectively. A CYP2D6 phenotype-genotype mismatch
      (phenocopying) can occur in Japanese psychiatric patients receiving clinical
      doses of some psychotropic drugs where the prevalence of PMs is low and the
      pharmacodynamic responses to those drugs are enhanced compared to Caucasian
      patients.

PMID- 14571355
TI  - Dosage finding and outcome of venlafaxine treatment in psychiatric outpatients
      and inpatients: results of a drug utilization observation study.
AB  - BACKGROUND: Venlafaxine is an antidepressive drug with the special characteristic
      of inhibiting both synaptic serotonin and norepinephrine reuptake. This double
      action is dosage dependent, with the relatively weaker inhibition of
      norepinephrine becoming clinically relevant only at higher dosages. This allows
      treatment to be tailored towards the needs of individual patients through
      differential dosing. It is unknown, however, how physicians use this unique
      feature in prescribing venlafaxine in routine treatment. METHOD: Data from a drug
      utilization observation (DUO) study, including 6706 patients, are used to
      investigate which patient and setting variables predict dosage of venlafaxine as
      prescribed by psychiatrists in inpatient and outpatient settings. Treatment
      outcome and adverse drug reactions (ADR) were analyzed for different dosage
      groups. RESULTS: Treatment setting is the most important factor in predicting
      high (> 75 mg/day) or low (up to 75 mg/day) dosage of venlafaxine, with
      inpatients receiving higher dosages. Severity of illness and a history of
      previous treatment with major antidepressives are also related to higher dosages.
      Although the total rate of ADR did not increase with increased dosage, the
      profile of drug reactions changed. Response to therapy was better in cases of non
      chronic, major depression with no treatment history of antidepressives.
      Additionally, increased dosage increased the likelihood of response in
      outpatients. In both settings, very high dosages predicted better response to
      venlafaxine among severely ill patients. CONCLUSION: Venlafaxine at a dosage of
      75 mg/day is sufficient for the majority of cases. In extremely ill patients,
      higher dosages are associated with additional benefits. Therefore, a stepwise
      dosage regimen is suggested, with an increase of dosage to upper limits in cases
      of non-response before discontinuation of treatment with venlafaxine.

PMID- 14571356
TI  - Risperidone-associated steatohepatitis and excessive weight-gain.
AB  - We report on a 17-year-old girl who developed steatohepatitis and marked weight
      gain during risperidone treatment for paranoid psychosis. Viral, metabolic, and
      other causes of liver disease were excluded. Although the exact mechanism of
      antipsychotic associated weight gain is unclear, the impact of risperidone on the
      serotonergic system and on neuropeptide Y, a stimulator of food intake, might be
      implicated in the development of obesity. Additionally, weight gain-related
      hyperleptinemia could be a link between overweight and hepatotoxicity via
      cytokines. Physicians should routinely monitor body weight, liver function,
      fasting blood glucose, and lipid profiles in children and adolescents at the
      beginning of risperidone therapy. Additionally, patients complaining about weight
      gain should be monitored more carefully during the maintenance phase.

PMID- 14571357
TI  - Fluoxetine in Alzheimer's disease with severe obsessive compulsive symptoms and a
      low density of serotonin transporter sites.
AB  - The treatment of behavioral disturbances is particularly challenging in patients
      suffering from dementia. In an 80-year-old female patient with probable AD and
      severe obsessive and compulsive symptoms, we demonstrated a significant reduction
      in the density of serotonin transporter sites using 1231-beta-CIT SPECT.
      Treatment with fluoxetine for 6 months resulted in significant symptom relief and
      an increasing density of serotonin transporter sites when compared to the
      beginning of treatment. Therefore, this report provides evidence that fluoxetine
      is a treatment option for patients with AD and severe obsessive-compulsive
      symptoms and highlights the importance of the serotoninergic system.

PMID- 14571358
TI  - [What does prevention and rehabilitation research contribute to health policy?].
AB  - Rational health policy calls for a close collaboration between health-related
      political organizations and scientific communities, in particular public health
      sciences and health economics. Based on selected examples, this contribution
      highlights the benefits of primary and secondary prevention measures with re
      spect to two widely distributed chronic diseases, coronary heart disease and
      depressive disorders. These examples refer to (1) lifestyle changes in secondary
      prevention of coronary heart disease, (2) theory-based measures of worksite
      health promotion, and (3)early detection and optimised treatment of depressive
      disorders. The relevance of interdisciplinary research on prevention and
      rehabilitation is emphasized by increasing pressures that arise from the current
      health care system.

PMID- 14571359
TI  - [Individual risk factors, health behaviour and mortality developments in Germany
      from 1984 to 1998].
AB  - The aim of the study is to investigate the contribution by the risk factors
      smoking, overweight, high blood pressure, physical inactivity and regular alcohol
      consumption to the total mortality development of the general population in
      Germany. Data are a mortality follow-up conducted by the Federal Institute for
      Population Research during 1984 - 1998 in West Germany and 1991-1998 in East
      Germany. 8474 persons participated at baseline in West Germany in the age group
      31-69 years, and 1546 persons participated at baseline in East Germany in the age
      group 40-79 years. The vital status in the year 1998 could be determined in West
      Germany for 86.5% and in East Germany for 97.0%. In the observation period 1986
      1998 for West Germany 17.2% of the males died and 8.6% of the females. In East
      Germany between 1991-1998 9.6% of the males died and 6.7% of the females. The
      statistical analysis, based on the Cox regression showed for West Germany except
      for overweight in males throughout a significant contribution of the risk factor
      load on total mortality. The highest relative risks were found for strong smokers
      (males: RR = 3.47, p < 0.001, females: RR = 3.62, p < 0.001). The relative
      mortality risk for persons with three and more risk factors yielded in males 4.88
      (p < 0.001) and in females 5.05 (p < 0.001). These findings clearly demonstrate
      that already a few risk markers of the individual health behaviour have a strong
      impact on the total mortality development in Germany. The mortality risk is about
      five times higher for persons with three and more risk factors. This indicates
      the need for preventive measures targeting high-risk population groups.

PMID- 14571360
TI  - [What kind of information is expected to be provided by medical information
      services?].
AB  - OBJECTIVE: The improvement of health-related information services is one major
      issue in reforming the German health care system to provide more transparency in
      health care services for patients and persons covered by the German statutory
      health insurance system. To meet the general need for specific medical
      information a telephone-based health information service may give individual
      advice and provide a helpful selection of information. The study aims at users
      expectations and preferences with regard to health information services. More
      particularly, users perception concerning the type of health information and the
      ways of choosing the information were to be explored. METHOD: The study included
      160 participants of different ages. Prototypical medical advice conversations
      were presented to the participants consisting of/identifying the consumer's
      inquiry, followed by the expert's answering sequence. The answers were based on
      typical inquiries from medical information providers focussing on treatment
      methods and illnesses. Health information from these conversations with its
      special contents were ranked by preference judgements resulting in Thurstone
      scalings. RESULTS: In terms of different health questions, the participants'
      judgements showed general preference structures for special health information,
      independent from any personal attitude towards medical information services.
      Great emphasis was placed on the medical conversation competence of the service
      provider, which is evident from recognising the specific needs and selection of
      information of a caller. Overall such health information was preferred that
      strengthened the patient's and user's autonomy and ability for decision making.
      CONCLUSION: Patients and persons covered by German statutory health insurance are
      characterised as users of information by special preferences. Identifying these
      preferences permits a reasonable selection of information and individual advice.
      Therefore, these services provide a major advantage over non-interactive health
      information services (print media, internet sites).

PMID- 14571361
TI  - [Unemployment, job insecurity and their consequences for health in a sample of
      young adults].
AB  - BACKGROUND: Negative consequences of unemployment have been known for a long
      time. This study concerns the effect of unemployment and job insecurity in a
      large sample of young adults because little is known about this special age
      group. Methods : 420 persons (46.8% males, 52.2% females, mean age 29 years) were
      polled in the 16(th) wave of the Sachsische Langsschnittstudie in 2002. This
      longitudinal study accompanies an East German sample since 1987 i.e. some time
      before German reunification. We used standardised psychological questionnaires to
      assess the state of health (SCL-9, HADS, GBB, SWE). RESULTS: 120 (29%) persons
      were repeatedly unemployed, 143 (34%) once, and only 157 (37%) have never been
      unemployed. The period of unemployment lasted 1 to 76 months. According to the
      experience with unemployment we found differences in subgroups: persons having
      more experience with unemployment report on higher global distress, more anxiety
      and depression, feel less efficacious and are in a subjectively poorer state of
      health. Nearly one-third of the participants think they have an insecure job.
      Persons who perceive an insecure job feel significantly greater anxiety,
      depression, body complaints, mental distress and feel less efficacious.
      CONCLUSIONS: Unemployment is a big social problem for young and well-qualified
      persons. The experience of unemployment decreases the identification with the
      current social system and has a strong negative influence on the state of health.
      Specific offers of medical and psychosocial support are required. Even the
      feeling of job insecurity has explicitly negative effects on health. Further
      longitudinal research is necessary.

PMID- 14571362
TI  - [Cost of miniplate osteosynthesis for treatment of mandibular fractures: a
      prospective evaluation].
AB  - PURPOSE: Up to now in maxillofacial surgery almost all inpatient treatments were
      reimbursed at the hospital's per diem rate. The real treatment cost is unknown
      and there is a lack of publications in this sphere. This study calculates the
      cost of surgical treatment of mandibular fractures. METHOD: The prospective study
      includes 104 patients whose mandibular fractures were treated using miniplate
      osteosynthesis. For each patient we took into account the time input by
      physicians and specialised nurses and calculated labour cost using the relevant
      wage rates. We added the cost for materials and drugs as well as for laboratory
      and radiographic examinations. Finally, we incorporated charges for the hotel and
      nursing components of inpatient treatment. RESULTS: The cost for the surgical
      treatment of mandibular fractures varied between 642 euro; for single and 1,070
      euro; for triple fractures. The share of labour cost is about 1/3. Treatment cost
      varies with the length of hospital stay: 1,132 euro; for four days and 1,628
      euro; for seven days on average. CONCLUSION: This prospective study can be
      compared with the recently published corresponding G-DRG rates. Moreover, the
      reported cost figures allow comparison with corresponding cost studies from other
      public health systems.

PMID- 14571363
TI  - [Guidelines and their practical application in congenital hearing loss].
AB  - BACKGROUND: Permanent congenital hearing loss in children does not only influence
      speech acquisition but also has a severe impact on the entire intellectual and
      psychological development, and thus social integration is handicapped. However,
      at least partial compensation can be achieved by complex rehabilitative measures.
      One of the first medical therapies in children with congenital hearing loss is to
      equip them with hearing aids. As part of quality management the purpose of this
      study is to discuss pedaudiological aspects and results of hearing - impaired
      children equipped with hearing aids against the background of guidelines from
      Germany and the US. METHODS: Data of 107 children equipped with hearing aids from
      1997 to 1999 were analysed referring to the relevant German and US guideline.
      RESULTS: In 53 girls and 54 boys, 45% were suffering from at least severe, 45%
      from moderate and 10% from mild hearing loss. 93 children presented sensory
      hearing loss, 8 combined and 2 conductive hearing loss. 2 children had unilateral
      hearing loss, one a combined on one ear and a sensory hearing loss on the other
      and one child had a central auditory processing disorder. The age when the
      hearing loss was diagnosed depended on its grade and correlated with adverse
      environmental aspects. 34 children suffered from a syndrome or multiple
      handicaps, in these cases, the hearing loss was diagnosed at a later date than in
      children suffering from hearing loss only. In cases with near deafness
      audiological results with hearing aids were not sufficient; in these cases,
      cochlea implantation had to be discussed as an alternative measure. CONCLUSION:
      The data obtained from this study underline the need for universal hearing
      screening. Discussing the data against the relevant German and US guidelines
      clearly shows that German benchmarks are not as strict as the American ones. This
      has to be taken into account for further guideline development in Germany. As
      permanent hearing loss in children with syndromes and multiple handicaps and
      children with adverse environment is diagnosed at a later date than in other
      children public, measures have to be taken to improve this situation.

PMID- 14571364
TI  - [What students and teaching doctors in Heidelberg think about early patient
      contact and tasks in general practice].
AB  - BACKGROUND: In Heidelberg, the clinical curriculum of medical education was
      fundamentally changed in 2001 due to co-operation with the Harvard Medical
      School. The pre-clinical curriculum has also already been undergoing reform since
      1995: the benefits of two new lectures with early patient contact and special
      tasks in the subject of family medicine were to be assessed. METHODS: In the
      first year, the students therefore had to assess the seminars, tutorials, and the
      internships in GP by means of a standardised questionnaire. In addition, reports
      had to be produced on teaching practice. The teachers were also questioned
      following agreement with and introduction of quality assurance measures. RESULTS:
      66-89% of students assigned good marks to the internships in GP, 40-58% for the
      accompanying seminars, and 70% for the tutors. The results of a general external
      evaluation which was carried out slightly differently were not quite so good. 87
      89% of teachers agreed upon the elaborated criteria for the quality of teaching
      practice. CONCLUSIONS: The results show that GP-based education is already well
      accepted in the first year of training, and that early patient contact in primary
      care is highly appreciated by the students. On their part, the teaching GPs
      assess the quality promotion sessions as instruments towards continuous quality
      support in pre-clinical training as meaningful and necessary, especially with
      regard to licensing for teaching in General practice.

PMID- 14571365
TI  - ["Problem-based learning--inflammation and transplantation": an integrated,
      subject-centred course in the clinical section of the medical curriculum at the
      medical school of the University of Muenster].
AB  - Conventional medical curricula present information pertinent to chronic
      inflammatory diseases, infectious diseases and transplantation, via systematic
      lectures and courses in medical specialties without any integrated approach. The
      authors report on a 3-week model course that attempts to provide students with an
      overview of clinical presentation, diagnostics, and therapy of representative
      disease entities with particular emphasis on the interdisciplinary approach to
      these problems in hospital practice. In addition to problem-based learning in
      small groups, the model course comprises interdisciplinary concept lectures,
      practical demonstrations of specific diagnostic procedures, and bedside teaching.
      In the meantime, the course "Problem-Based Learning--Inflammation and
      Transplantation" has been held twice successfully as a mandatory course in the
      clinical part of the curriculum at the Muenster Medical School.

PMID- 14571366
TI  - [The German Quality Management System for Outpatient Care (Q-M-A) Checklist--an
      instrument for assessing quality management systems in outpatient care].
AB  - Quality management systems had originally been designed for industrial purposes
      and were hardly applicable for small enterprises, there have been adjustments to
      the two main applications EFQM and ISO enabling utilisation also in ambulatory
      care. There are also different approaches like the Dutch Visitatiae concept which
      reflects the needs of GP's and is based on peer exchange. The presented paper
      gives an overview of existing quality management and certification systems and
      presents an instrument for evaluation. This checklist was developed by an
      interdisciplinary expert panel of the Agency for Quality in Medicine and serves
      as an aid for users and graders of quality management systems with regard to the
      feasibility of these systems.

PMID- 14571367
TI  - [Prevention--the local health department as a decentralized center].

PMID- 14571369
TI  - A string pattern regression algorithm and its application to pattern discovery in
      long introns.
AB  - We present a new approach to pattern discovery called string pattern regression,
      where we are given a data set that consists of a string attribute and an
      objective numerical attribute. The problem is to find the best string pattern
      that divides the data set in such a way that the distribution of the numerical
      attribute values of the set for which the pattern matches the string attribute,
      is most distinct, with respect to some appropriate measure, from the distribution
      of the numerical attribute values of the set for which the pattern does not match
      the string attribute. By solving this problem, we are able to discover, at the
      same time, a subset of the data whose objective numerical attributes are
      significantly different from rest of the data, as well as the splitting rule in
      the form of a string pattern that is conserved in the subset. Although the
      problem can be solved in linear time for the substring pattern class, the problem
      is NP-hard in the general case (i.e. more complex patterns), and we present an
      exact but efficient branch-and-bound algorithm which is applicable to various
      pattern classes. We apply our algorithm to intron sequences of human, mouse, fly,
      and zebrafish, and show the practicality of our approach and algorithm. We also
      discuss possible extensions of our algorithm, as well as promising applications,
      such as microarray gene expression data.

PMID- 14571370
TI  - A novel bioinformatic strategy for unveiling hidden genome signatures of
      eukaryotes: self-organizing map of oligonucleotide frequency.
AB  - With the increasing amount of available genome sequences, novel tools are needed
      for comprehensive analysis of species-specific sequence characteristics for a
      wide variety of genomes. We used an unsupervised neural network algorithm,
      Kohonen's self-organizing map (SOM), to analyze di- and trinucleotide frequencies
      in 9 eukaryotic genomes of known sequences (a total of 1.2 Gb); S. cerevisiae, S.
      pombe, C. elegans, A. thaliana, D. melanogaster, Fugu, and rice, as well as P.
      falciparum chromosomes 2 and 3, and human chromosomes 14, 20, 21, and 22, that
      have been almost completely sequenced. Each genomic sequence with different
      window sizes was encoded as a 16- and 64-dimensional vector giving relative
      frequencies of di- and trinucleotides, respectively. From analysis of a total of
      120,000 nonoverlapping 10-kb sequences and overlapping 100-kb sequences with a
      moving step size of 10 kb, derived from a total of the 1.2 Gb genomic sequences,
      clear species-specific separations of most sequences were obtained with the SOMs.
      The unsupervised algorithm could recognize, in most of the 120,000 10-kb
      sequences, the species-specific characteristics (key combinations of
      oligonucleotide frequencies) that are signature representations of each genome.
      Because the classification power is very high, the SOMs can provide fundamental
      bioinformatic strategies for extracting a wide range of genomic information that
      could not otherwise be obtained.

PMID- 14571371
TI  - Detection of periodicity in eukaryotic genomes on the basis of power spectrum
      analysis.
AB  - In the present study, we identified periodic patterns in nucleotide sequence, and
      characterized nucleotide sequences that confer periodicities to Arabidopsis
      thaliana and Drosophila melanogaster on the basis of a power spectrum method and
      frequency of nucleotide sequences. To assign regions that contribute to each
      periodicity we calculated periodic nucleotide distributions by a parameter
      proposed in the paper. In A. thaliana, we obtained three periodicities (248 bp-,
      167 bp-, and 126 bp) in chromosome 3, three peaks (174 bp-, 88 bp-, and 59 bp
      period) in chromosome 4, and four periodicities (356 bp, 174 bp, 88 bp, and 59
      bp) in chromosome 5. These are relation to ORF that consists of Gly-rich amino
      acid sequences including histone protein that consists of Gly-, Ser-, and Ala
      rich amino acids residues. For D. melanogaster genome we found that G or C
      spectral curves have flat region at middle frequency range from f = 10(-4) to 10(
      5) (corresponding to cyclic size 1 kb-5 kb), which may be associated with
      randomness of base sequence composition. This property has not been observed in
      Saccharomyces cerevisiae, Caenorhabditis elegans, and Homo sapiens yet.

PMID- 14571368
TI  - Prevalence and evolutionary origins of the del(GJB6-D13S1830) mutation in the
      DFNB1 locus in hearing-impaired subjects: a multicenter study.
AB  - Mutations in GJB2, the gene encoding connexin-26 at the DFNB1 locus on 13q12, are
      found in as many as 50% of subjects with autosomal recessive, nonsyndromic
      prelingual hearing impairment. However, genetic diagnosis is complicated by the
      fact that 10%-50% of affected subjects with GJB2 mutations carry only one mutant
      allele. Recently, a deletion truncating the GJB6 gene (encoding connexin-30),
      near GJB2 on 13q12, was shown to be the accompanying mutation in approximately
      50% of these deaf GJB2 heterozygotes in a cohort of Spanish patients, thus
      becoming second only to 35delG at GJB2 as the most frequent mutation causing
      prelingual hearing impairment in Spain. Here, we present data from a multicenter
      study in nine countries that shows that the deletion is present in most of the
      screened populations, with higher frequencies in France, Spain, and Israel, where
      the percentages of unexplained GJB2 heterozygotes fell to 16.0%-20.9% after
      screening for the del(GJB6-D13S1830) mutation. Our results also suggest that
      additional mutations remain to be identified, either in DFNB1 or in other
      unlinked genes involved in epistatic interactions with GJB2. Analysis of
      haplotypes associated with the deletion revealed a founder effect in Ashkenazi
      Jews and also suggested a common founder for countries in Western Europe. These
      results have important implications for the diagnosis and counseling of families
      with DFNB1 deafness.

PMID- 14571372
TI  - Analysis of common k-mers for whole genome sequences using SSB-tree.
AB  - As sequenced genomes become larger and sequencing process becomes faster, there
      is a need to develop a tool to analyze sequences in the whole genomic scale.
      However, on-memory algorithms such as suffix tree and suffix array are not
      applicable to the analysis of whole genome sequence set, since the size of
      individual whole genome ranges from several million base pairs to hundreds
      billion base pairs. In order to effectively manipulate the huge sequence data, it
      is necessary to use the indexed data structure for external memory. In this
      paper, we introduce a workbench called SequeX for the analysis and visualization
      of whole genome sequences using SSB-tree (Static SB-tree). It consists of two
      parts: the analysis query subsystem and the visualization subsystem. The query
      subsystem supports various transactions such as pattern matching, k-occurrence,
      and k-mer analysis. The visualization subsystem helps biologists to easily
      understand whole genome structure and feature by sequence viewer, annotation
      viewer, CGR (Chaos Game Representation) viewer, and k-mer viewer. The system also
      supports a user-friendly programming interface based on Java script for batch
      processing and the extension for a specific purpose of a user. SequeX can be used
      to identify conserved genes or sequences by the analysis of the common k-mers and
      annotation. We analyze the common k-mer for 72 microbial genomes announced by
      Entrez, and find an interesting biological fact that the longest common k-mer for
      72 sequences is 11-mer, and only 11 such sequences exist. Finally we note that
      many common k-mers occur in conserved region such as CDS, rRNA, and tRNA.

PMID- 14571373
TI  - Large scale statistical prediction of protein-protein interaction by potentially
      interacting domain (PID) pair.
AB  - Protein-protein interaction plays a critical role in biological processes. The
      identification of interacting proteins by computational methods can provide new
      leads in functional studies of uncharacterized proteins without performing
      extensive experiments. We developed a database for the potentially interacting
      domain pairs (PID) extracted from a dataset of experimentally identified
      interacting protein pairs (DIP: database of interacting proteins) with InterPro,
      an integrated database of protein families, domains and functional sites. In
      developing protein interaction databases and predictive methods, sensitive
      statistical scoring systems is critical to provide a reliability index for
      accurate functional analysis of interaction networks. We present a statistical
      scoring system, named "PID matrix score" as a measure of the interaction
      probability (interactability) between domains. This system provided a valuable
      tool for functional prediction of unknown proteins. For the evaluation of PID
      matrix, cross validation was performed with subsets of DIP data. The prediction
      system gives about 50% sensitivity and more than 98% specificity, which implies
      that the information for interacting proteins pairs could be enriched about 30
      fold with the PID matrix. It is demonstrated that mapping of the genome-wide
      interaction network can be achieved by using the PID matrix.

PMID- 14571374
TI  - A comparative study on feature selection and classification methods using gene
      expression profiles and proteomic patterns.
AB  - Feature selection plays an important role in classification. We present a
      comparative study on six feature selection heuristics by applying them to two
      sets of data. The first set of data are gene expression profiles from Acute
      Lymphoblastic Leukemia (ALL) patients. The second set of data are proteomic
      patterns from ovarian cancer patients. Based on features chosen by these methods,
      error rates of several classification algorithms were obtained for analysis. Our
      results demonstrate the importance of feature selection in accurately classifying
      new samples.

PMID- 14571375
TI  - Extraction of organism groups from phylogenetic profiles using independent
      component analysis.
AB  - In recent years, the analysis of orthologous genes based on phylogenetic profiles
      has received popularity in bioinfomatics. We propose a new method to extract
      organism groups and their hierarchy from phylogenetic profiles using the
      independent component analysis (ICA). The method involves first finding
      independent axes in the projected space from the multivariate data matrix
      representing phylogenetic profiles for a number of orthologous genes. Then the
      extracted axes are correlated with major organism groups, according to the extent
      of affiliation of axes scores for all the genes to specific organisms. The ICA
      was applied to the phylogenetic profiles created for 2,875 orthologs in 77
      organisms by using the KEGG/GENES database. The 9 extracted components out of 18
      predefined components well represented the organism groups as categorized in
      KEGG. Furthermore, we performed the cluster analysis and obtained the hierarchy
      of organism groups.

PMID- 14571376
TI  - Origin of most primitive mRNAs and genetic codes via interactions between
      primitive tRNA ribozymes.
AB  - The origin and early evolution of genetic codon system and early mRNAs were
      analyzed from a viewpoint of primordial gene theory and the poly-tRNA theory. A
      hypothetical 25-amino acid (aa)-primordial peptide was deduced from internal aa
      sequence homology of adenylate kinases. Theoretical models were made which can
      reasonably explain how primitive tRNA(s) could have had converted to be earliest
      mRNAs via interactions between presumptive anticodons and (poly-)tRNA ribozyme.
      Transfer-RNA gene clusters in the trrnD- and rrnB-operons of Bacillus subtilis
      seemed to be relics of early peptide-synthesizing RNA machine. Detailed analyses
      revealed that the poly-tRNA regions in these operons are true relics of RNA
      machine for making a 16-aa trrnD-peptide and a 21-aa rrnB-peptide, whose aa
      sequences are in the order of aa specificities of tRNAs in the tRNA gene clusters
      of the trrnD-operon and rrnB-operon, respectively. The primordial gene-encoded
      peptide deduced from adenylate kinases were found to be a genuine homologue of
      the rrnB-peptide. Various protein superfamilies were found to have evolved from
      either of these two types of primitive peptides. Earliest mRNAs were concluded to
      have evolved from tRNAGly (trrnD-mRNA) or tRNAHis (rrnB-mRNA), where trrnD- and
      rrnB-mRNAs are hypothetical primitive mRNAs complementary to the tandem
      arrangement of 16 or 21 anticodons of tRNAs in the trrnD-operon and rrnB-operon,
      respectively. The poly-tRNA model is considered to be an excellent theory,
      because it can reasonably explain origins of both genetic codes and earliest
      mRNAs, and because the hypothesis can be statistically evaluated by base-identity
      levels in proper alignments. The genetic codon system is a typical mature
      semeiotic system within a cell, and the genesis of the genetic codon system was
      discussed from an aspect of de Saussure's semeiology. Arbitrary correspondence
      between (anti)codon and aa would be most plausibly a result of semeiotic culture
      system of intracellular tRNA-riboorganismic society.

PMID- 14571377
TI  - Very fast algorithms for evaluating the stability of ML and Bayesian phylogenetic
      trees from sequence data.
AB  - Evolutionary trees sit at the core of all realistic models describing a set of
      related sequences, including alignment, homology search, ancestral protein
      reconstruction and 2D/3D structural change. It is important to assess the
      stochastic error when estimating a tree, including models using the most
      realistic likelihood-based optimizations, yet computation times may be many days
      or weeks. If so, the bootstrap is computationally prohibitive. Here we show that
      the extremely fast "resampling of estimated log likelihoods" or RELL method
      behaves well under more general circumstances than previously examined. RELL
      approximates the bootstrap (BP) proportions of trees better that some bootstrap
      methods that rely on fast heuristics to search the tree space. The BIC
      approximation of the Bayesian posterior probability (BPP) of trees is made more
      accurate by including an additional term related to the determinant of the
      information matrix (which may also be obtained as a product of gradient or score
      vectors). Such estimates are shown to be very close to MCMC chain values. Our
      analysis of mammalian mitochondrial amino acid sequences suggest that when model
      breakdown occurs, as it typically does for sequences separated by more than a few
      million years, the BPP values are far too peaked and the real fluctuations in the
      likelihood of the data are many times larger than expected. Accordingly, several
      ways to incorporate the bootstrap and other types of direct resampling with MCMC
      procedures are outlined. Genes evolve by a process which involves some sites
      following a tree close to, but not identical with, the species tree. It is seen
      that under such a likelihood model BP (bootstrap proportions) and BPP estimates
      may still be reasonable estimates of the species tree. Since many of the methods
      studied are very fast computationally, there is no reason to ignore stochastic
      error even with the slowest ML or likelihood based methods.

PMID- 14571378
TI  - An algorithmic analysis of the role of unequal crossover in alpha-satellite DNA
      evolution.
AB  - Human DNA consists of a large number of tandem repeat sequences. Such sequences
      are usually called satellites, with the primary example being the centromeric
      alpha-satellite DNA. The basic repeat unit of the alpha-satellite DNA is a 171 bp
      monomer. However, with the exception of peripheral alpha-satellite DNA, monomers
      can be grouped into blocks of k-monomers (4 < k < 20) between which the
      divergence rate is much smaller (e.g. 5%). Perhaps the simplest and best
      understood mechanism for tandem repeat array evolution is the unequal crossover.
      Although it is possible that the alpha-satellite sequence developed as a result
      of subsequent unequal crossovers only, no formal computational framework seems to
      have been developed to verify this possibility. In this paper we develop such a
      framework and perform experiments which seem to indicate that pericentromeric
      alpha-satellite segments (which are devoid of higher-order structure) are
      evolutionarily distinct from the higher-order repeat segments. It is likely that
      the higher order repeats developed independently in distinct regions of the
      genome and were carried into their current locations through an unknown mechanism
      of transposition.

PMID- 14571379
TI  - Genomic sorting with length-weighted reversals.
AB  - Current algorithmic studies of genome rearrangement ignore the length of
      reversals (or inversions); rather, they only count their number. We introduce a
      new cost model in which the lengths of the reversed sequences play a role,
      allowing more flexibility in accounting for mutation phenomena. Our focus is on
      sorting unsigned (unoriented) permutations by reversals; since this problem
      remains difficult (NP-hard) in our new model, the best we can hope for are
      approximation results. We propose an efficient, novel algorithm that takes (a
      monotonic function f of) length into account as an optimization criterion and
      study its properties. Our results include an upper bound of O(fn lg2n) for any
      additive cost measure f on the cost of sorting any n-element permutation, and a
      guaranteed approximation ratio of O(lg2n) times optimal for sorting a given
      permutation. Our work poses some interesting questions to both biologists and
      computer scientists and suggests some new bioinformatic insights that are
      currently being studied.

PMID- 14571381
TI  - Aligning multiple protein sequences by parallel hybrid genetic algorithm.
AB  - This paper presents a parallel hybrid genetic algorithm (GA) for solving the sum
      of-pairs multiple protein sequence alignment. A new chromosome representation and
      its corresponding genetic operators are proposed. A multi-population GENITOR-type
      GA is combined with local search heuristics. It is then extended to run in
      parallel on a multiprocessor system for speeding up. Experimental results of
      benchmarks from the BAliBASE show that the proposed method is superior to MSA,
      OMA, and SAGA methods with regard to quality of solution and running time. It can
      be used for finding multiple sequence alignment as well as testing cost
      functions.

PMID- 14571380
TI  - Marginalized kernels for RNA sequence data analysis.
AB  - We present novel kernels that measure similarity of two RNA sequences, taking
      account of their secondary structures. Two types of kernels are presented. One is
      for RNA sequences with known secondary structures, the other for those without
      known secondary structures. The latter employs stochastic context-free grammar
      (SCFG) for estimating the secondary structure. We call the latter the
      marginalized count kernel (MCK). We show computational experiments for MCK using
      74 sets of human tRNA sequence data: (i) kernel principal component analysis
      (PCA) for visualizing tRNA similarities, (ii) supervised classification with
      support vector machines (SVMs). Both types of experiment show promising results
      for MCKs.

PMID- 14571382
TI  - Inference of Euler angles for single particle analysis by using Genetic
      Algorithms.
AB  - Single particle analysis is one of the methods for structural studies of protein
      and macromolecules developed in image analysis on electron microscopy.
      Reconstructing 3D structure from microscope images is not an easy analysis
      because of the low resolution of images and lack of the directional information
      of images in 3D structure. To improve the resolution, different projections are
      aligned, classified and averaged. Inferring the orientations of these images is
      so difficult that the task of reconstructing 3D structures depends upon the
      experience of researchers. But recently, a method to reconstruct 3D structures is
      automatically devised. In this paper, we propose a new method for determining
      Euler angles of projections by applying Genetic Algorithms (i.e., GAs). We
      empirically show that the proposed approach has improved the previous one in
      terms of computational time and acquired precision.

PMID- 14571383
TI  - Point matching under non-uniform distortions and protein side chain packing based
      on an efficient maximum clique algorithm.
AB  - We developed maximum clique-based algorithms for spot matching for two
      dimensional gel electrophoresis images, protein structure alignment and protein
      side-chain packing, where these problems are known to be NP-hard. Algorithms
      based on direct reductions to the maximum clique can find optimal solutions for
      instances of size (the number of points or residues) up to 50-150 using a
      standard PC. We also developed pre-processing techniques to reduce the sizes of
      graphs. Combined with some heuristics, many realistic instances can be solved
      approximately.

PMID- 14571384
TI  - The role of DNA deformation energy at individual base steps for the
      identification of DNA-protein binding sites.
AB  - We examine the use of deformation propensity at individual base steps for the
      identification of DNA-protein binding sites. We have previously demonstrated that
      estimates of the total energy to bend DNA to its bound conformation can partially
      explain indirect DNA-protein interactions. We now show that the deformation
      propensities at each base step are not equally informative for classifying a
      sequence as a binding site, and that applying non-uniform weights to the
      contribution of each base step to aggregate deformation propensity can greatly
      improve classification accuracy. We show that a perceptron can be trained to use
      the deformation propensity at each step in a sequence to generate such weights.

PMID- 14571385
TI  - Folding pattern recognition in proteins using spectral analysis methods.
AB  - Divergence in sequence through evolution precludes sequence alignment based
      homology methodologies for protein folding prediction from detecting structural
      and folding similarities for distantly related protein. Homolog coverage of
      actual data bases is also a factor playing a critical role in the performance of
      those methodologies, the factor being conspicuously apparent in what is called
      the twilight zone of sequence homology in which proteins of high degree of
      similarity in both biological function and structure are found but for which the
      amino acid sequence homology ranges from about 20% to less than 30%. In contrast
      to these methodologies a strategy is proposed here based on a different concept
      of sequence homology. This concept is derived from a periodicity analysis of the
      physicochemical properties of the residues constituting proteins primary
      structures. The analysis is performed using a front-end processing technique in
      automatic speech recognition by means of which the cepstrum (measure of the
      periodic wiggliness of a frequency response) is computed that leads to a spectral
      envelope that depicts the subtle periodicity in physicochemical characteristics
      of the sequence. Homology in sequences is then derived by alignment of spectral
      envelopes. Proteins sharing common folding patterns and biological function but
      low sequence homology can then be detected by the similarity in spectral
      dimension. The methodology applied to protein folding recognition underscores in
      many cases other methodologies in the twilight zone.

PMID- 14571386
TI  - Comparative analysis of the genomes of cyanobacteria and plants.
AB  - Chloroplast genome originates from the genome of ancestral cyanobacterial
      endosymbiont. The comparison of the genomes of cyanobacteria and plants has been
      made possible by the advance in genome sequencing. I report here current results
      of our computational efforts to compare the genomes of cyanobacteria and plants
      and to trace the process of evolution of cyanobacteria, chloroplasts and plants.
      Cyanobacteria form a clearly defined monophyletic clade with reasonable level of
      diversity and are ideal for testing various approaches of genome comparison.
      Analysis of short sequence features such as genome signature was found to be
      useful in characterizing cyanobacterial genomes. Comparison of genome contents
      was performed by homology grouping of predicted protein coding sequences, rather
      than orthologue-based comparison, to minimize effects of multi-domain proteins
      and large protein families, both of which are important in cyanobacterial
      genomes. Comparison of the genomes of six species of cyanobacteria suggests that
      there are a number of species-specific additions of protein genes, and this
      information is useful in reconstructing phylogenetic relationship. The homology
      groups in cyanobacteria were used as a reference to compare plants and non
      photosynthetic organisms. The results suggest that 238 groups that are common to
      all organisms analyzed may define a minimal set of gene groups. In addition, only
      80 groups are identified as the gene groups that could not have been acquired by
      plants without cyanobacterial endosymbiosis. Further study is needed to identify
      plant genes of cyanobacterial origin.

PMID- 14571387
TI  - A novel index which precisely derives protein coding regions from cross-species
      genome alignments.
AB  - We introduce here a novel index which precisely derives protein coding regions
      from cross-species genome alignments. The index is deeply related to frame
      recovery observed in coding sequence alignments, that is, if insertions or
      deletions of nucleotides causes frame shifts in coding regions, other in-dels
      which recover the reading frames will be often observed in the vicinity. In
      contrast, such frame recoveries are not observed in other conserved regions. We
      prepared two gene models: a model which finds gene by using sequence similarity
      and intrinsic gene measures (basic model), and the other model which finds gene
      by using frame recovery index in addition to sequence similarity and intrinsic
      gene measures (frame recovery model). We evaluated the prediction accuracies of
      the two models, and our benchmark test revealed that frame recovery model
      significantly improved the prediction accuracy in comparison with basic model.

PMID- 14571388
TI  - Using feature generation and feature selection for accurate prediction of
      translation initiation sites.
AB  - Correct prediction of the translation initiation site (TIS) is an important issue
      in genomic research. We show that feature generation together with correlation
      based feature selection can be used with a variety of machine learning algorithms
      to give highly accurate translation initiation site prediction. Only very few
      features are needed and the results achieve comparable accuracy to the best
      existing approaches. Our approach has the advantage that it does not require one
      to devise a special prediction method; rather standard machine learning
      classifiers are shown to give very good performance on the selected features. The
      raw and generated features which we have found to be important are the following:
      positions -3 and -1 in the sequence; upstream k-grams for k=3, 4, and 5; stop
      codon frequency; downstream in-frame 3-gram; and the distance of ATG to the
      beginning of the sequence. The best result, with an overall accuracy of 90%, is
      obtained by selecting only seven features from this set. The same features
      retrained with the use of a scanning model achieves an overall accuracy of 94% on
      this dataset.

PMID- 14571389
TI  - Automatic ontology construction from the literature.
AB  - Detailed classifications, controlled vocabularies and organised terminology are
      widely used in different areas of science and technology. Their relatively recent
      introduction in molecular biology has been crucial for progress in the analysis
      of genonics and massive proteomics experiments. Unfortunately the construction of
      the ontologies, including terminology, classification and entity relations
      requires considerable effort, including the analysis of massive amounts of
      literature. We propose here a method that automatically generates classifications
      of gene-product functions using bibliographic information. The corresponding
      classification structures mirror the ones constructed by human experts. The
      analysis of a large structure built for yeast gene-products, and the detailed
      inspection of various examples, show encouraging properties. In particular, the
      comparison with the well accepted GO ontology points to different situations in
      which the automatically derived classification can be useful for assisting human
      experts in the annotation of ontologies.

PMID- 14571390
TI  - In silico metabolic pathway analysis and design: succinic acid production by
      metabolically engineered Escherichia coli as an example.
AB  - The intracellular metabolic fluxes can be calculated by metabolic flux analysis,
      which uses a stoichiometric model for the intracellular reactions along with mass
      balances around the intracellular metabolites. In this study, we have constructed
      in silico metabolic pathway network of Escherichia coli consisting of 301
      reactions and 294 metabolites. Metabolic flux analyses were carried out to
      estimate flux distributions to achieve the maximum in silico yield of succinic
      acid in E. coli. The maximum in silico yield of succinic acid was only 83% of its
      theoretical yield. The lower in silico yield of succinic acid was found to be due
      to the insufficient reducing power, which could be increased to its theoretical
      yield by supplying more reducing power. Furthermore, the optimal metabolic
      pathways for the production of succinic acid could be proposed based on the
      results of metabolic flux analyses. In the case of succinic acid production, it
      was found that pyruvate carboxylation pathway should be used rather than
      phosphoenolpyruvate carboxylation pathway for its optimal production in E. coli.
      Then, the in silico optimal succinic acid pathway was compared with conventional
      succinic acid pathway through minimum set of wet experiments. The results of wet
      experiments indicate that the pathway predicted by in silico analysis is more
      efficient than conventional pathway.

PMID- 14571391
TI  - Physical modeling of the cellular arrangement in C. elegans early embryo: effect
      of rounding and stiffening of the cells.
AB  - The ultimate goal of bioinformatics is to reconstruct biological systems in a
      computer. Biological systems have a multi-scale and multi-level biological
      hierarchy. The cellular level of the hierarchy is appropriate and practicable for
      reconstructing biological systems by computer modeling. In our first application
      of computer modeling to development of the nematode C. elegans, we focus on the
      cellular arrangement in early embryos. This plays a very important role in cell
      fate determination by cell-cell interaction, which is largely restricted by
      physical conditions. We have already constructed a computer model of a C. elegans
      embryo, currently up to the 4-cell stage, using deformable and dividable
      geometric graphics. Modeling components of the embryo are based solely on
      cellular-level dynamics. Here, we modeled new physical phenomena of cell
      division, cell rounding and stiffening; we then combined them with already
      modeled phenomena, contractile ring contraction and cell elongation. We
      investigated effectiveness of the new model on cellular arrangement by computer
      simulations. We found that cell rounding and stiffening only during the period of
      cell division were effective to generate almost identical cellular arrangements
      to in real embryos. Since cells could be soft during the period between cell
      divisions, implementation of the new model resulted in cell shapes similar to
      real embryos. The nature of the model and its relationship to real embryos are
      discussed.

PMID- 14571392
TI  - Risks associated with the use of intravenous immunoglobulin.
AB  - Although US immune globulin intravenous (human) (IGIV) products have been
      regarded as safe, it is important to recognize that many of the controlled
      clinical studies of IGIVs have been of modest size and have limited power to
      define the incidence of only the most common adverse events (AEs). A significant
      number of "postmarketing" serious AEs affecting renal, cardiovascular, CNS,
      integumentary, and hematologic organ systems have been reported. Variables
      potentially affecting the risk and intensity of adverse events associated with
      administration of IGIV include patient age, underlying condition, history of
      migraine, cardiovascular or renal disease, dose, concentration, rate of infusion,
      specific brand/formulation/excipients, and lot(s) of the particular IGIV product
      being administered. Each manufacturer's IGIV preparation is a unique product
      carrying its own specific evidence-based indications and safety profile. In view
      of the seriousness of potential adverse effects of IGIV products, and current
      lack of data surrounding their frequency, clinicians are advised to limit their
      prescription of these products for conditions for which efficacy is supported by
      adequate and well-controlled clinical trials. Prescribers should pay close
      attention to patient selection; consider the potential risk/benefit ratio vis-a
      vis alternate therapies; and familiarize themselves with the identification,
      management, and proposed strategies to minimize the risks of IGIV.

PMID- 14571393
TI  - Transfusion-related acute lung injury.
AB  - Transfusion-related acute lung injury (TRALI) is an uncommon complication of
      allogeneic blood transfusion manifested typically by shortness of breath, fever,
      and hypotension. It has been estimated to occur in 0.04% to 0.16% per patient
      transfused. TRALI has been identified as an important cause of transfusion
      related morbidity and mortality. Despite the increasing recognition that TRALI
      represents an important clinical syndrome, much about the pathogenesis,
      treatment, and prevention of TRALI is poorly understood or is controversial. In
      this report, what is known about TRALI is summarized and some of the areas in
      which knowledge and/or consensus are currently lacking are identified.

PMID- 14571394
TI  - Effects of blood product storage protectants on blood coagulation.
AB  - The ever-increasing demand for blood products challenges scientists to develop
      new and more effective techniques for their preservation. The progress of these
      novel preservation technologies uses a wide variety of cryoprotectant,
      lyoprotectant, and other preservatives, which will need to be explored and
      assessed for their biological effects during blood product formulation. The
      leading factor in protectant selection is for their ability to provide superior
      preservation for a particular blood product. We believe that such protectants
      used in blood product development should also be evaluated for their ability to
      preserve normal hemostasic mechanisms. In this review, high-molecular-weight
      cryoprotectants, lyoprotectants, polyols, amino acids, antioxidants, and
      surfactants, used because of their protective properties, were evaluated for
      their possible role in relation to their effect on normal hemostatic mechanisms.

PMID- 14571395
TI  - Gastrointestinal bleeding, angiodysplasia, cardiovascular disease, and acquired
      von Willebrand syndrome.
AB  - Recent evidence points to isolated deficiency of the largest multimers of von
      Willebrand factor (VWF)-known as von Willebrand syndrome type 2A (VWS-2A)-as a
      risk factor for bleeding from gastrointestinal (GI) angiodysplasia. This disorder
      is not widely recognized, perhaps because most patients do not exhibit
      generalized hemostatic impairment (bleeding is generally restricted to GI
      angiodysplasia) and because all but the largest multimers of VWF remain
      detectable in the plasma (thus, routine screening tests for VWS-2A are usually
      normal). The "Rosetta stone" for elucidating this syndrome was the enigma of
      Heyde's syndrome (aortic stenosis plus bleeding GI angiodysplasia), particularly
      the striking observation that aortic valve replacement generally cures GI
      bleeding and that preoperative deficiency of the largest VWF multimers undergoes
      long-term normalization after valve replacement. We critically review the
      evidence implicating VWS-2A as a risk factor for bleeding GI angiodysplasia. We
      hypothesize that VWS-2A secondary to cardiovascular disease other than severe
      aortic stenosis, such as peripheral arterial occlusive disease, could explain why
      elderly patients often develop recurrent GI bleeding or iron deficiency anemia
      from GI angiodysplasia.

PMID- 14571396
TI  - Evolution of fibrin glue applicators.
AB  - Fibrin glue (FG) is used worldwide as a potent surgical tool, which establishes
      hemostasis in wounds and also bonds tissue. The standard FG applicator is based
      on a dual-syringe system. This review, based mainly on the patent literature,
      describes the development of the quasi-standard dual syringe system as well as
      the rise of other FG applicator designs based on mechanical force (ratchet
      systems), Bernoulli gas flow, positive gas pressure, or electro-servo devices.
      The packaging of commercial FG components is reviewed within the context of
      "loading" the FG applicators and the need to minimize the number of needles
      required to access the packaged (vials) components. Parameters such as internal
      clogging, homogeneity of spray, the requirement for gas or vacuum house lines,
      the number of parts that must be handled, and the time required to assemble the
      applicator, load it, and have it ready for use are also discussed. A rating
      system is proposed that permits one to use such parameters to rank the various
      applicator designs, relative to the dual-syringe system. Hopefully, this review
      will stimulate the design of better FG applicators and packaging required for
      elective surgery, emergency treatments, and tissue engineering in the 21st
      century.

PMID- 14571406
TI  - The case for a biologically based classification of prostate cancer.
AB  - It is axiomatic that integrated multidisciplinary therapy based on the
      understanding of malignancy is required for the cure of adult cancer. In
      successful examples, agents (chemotherapy, biologics) and other modalities
      (radiation, surgery) are applied on the basis of clinical biology. The
      understanding of the clinical biology and the development of a classification
      based on relevant clinical and biological features is central to therapy
      development.

PMID- 14571407
TI  - Predicting clinical end points: treatment nomograms in prostate cancer.
AB  - Due to the generally indolent nature of prostate cancer, patients must decide
      among a wide range of treatments, which will significantly affect both quality of
      life and survival. Thus, there is a need for instruments to aid patients and
      their physicians in decision analysis. Nomograms are instruments that predict
      outcomes for the individual patient. Using algorithms that incorporate multiple
      variables, nomograms calculate the predicted probability that a patient will
      reach a clinical end point of interest. Nomograms tend to outperform both expert
      clinicians and predictive instruments based on risk grouping. We outline
      principles for nomogram construction, including considerations for choice of
      clinical end points and appropriate predictive variables, and methods for model
      validation. Currently, nomograms are available to predict progression-free
      probability after several primary treatments for localized prostate cancer. There
      is need for additional models that predict other clinical end points, especially
      survival adjusted for quality of life.

PMID- 14571408
TI  - Conservative versus radical therapy of prostate cancer: how have recent advances
      in molecular markers and imaging enhanced our ability to prognosticate risk?
AB  - Recent results of several prospective phase II and phase III trials have
      reinforced the view that many patients with favorable-risk prostate cancer are
      over treated. The challenge is to identify those patients who require treatment
      at a point at which they are still amenable to cure, and to avoid treating those
      who have indolent disease and those who are incurable. This requires a
      combination of early detection, accurate imaging, and a selective approach to
      therapy. The accuracy of serum and tissue biomarkers and new imaging techniques
      in stratifying patients according to the risk of progression and metastasis is
      reviewed. The outcome of a strategy of selective intervention in good-risk
      patients based on prostate-specific antigen (PSA) doubling time is summarized.

PMID- 14571409
TI  - Technological advances in external-beam radiation therapy for the treatment of
      localized prostate cancer.
AB  - The relative inability of conventional radiotherapy to control localized prostate
      cancer results from resistance of subpopulations of tumor clonogens to dose
      levels of 65 to 70 Gy, the maximum feasible with traditional two-dimensional (2D)
      treatment planning and delivery techniques. Several technological advances have
      enhanced the precision and improved the outcome of external-beam radiotherapy.
      The three-dimensional conformal radiotherapy (3D-CRT) approach has permitted
      significant increases in the tumor dose to levels beyond those feasible with
      conventional techniques. Intensity-modulated radiotherapy (IMRT), an advanced
      form of conformal radiotherapy, has resulted in reduced rectal toxicity,
      permitting tumor dose escalation to previously unattainable levels with a
      concomitant improvement in local tumor control and disease-free survival. The
      combination of androgen deprivation and conventional-dose radiotherapy, tested
      mainly in patients with locally advanced disease, has also produced significant
      outcome improvements. Whether androgen deprivation will preclude the need for
      dose escalation or whether high-dose radiotherapy will obviate the need for
      androgen deprivation remains unknown. In some patients, both approaches may be
      necessary to maximize the probability of cure. In view of the favorable benefit
      risk ratio of high-dose IMRT, the design of clinical trials to resolve these
      critical questions is essential.

PMID- 14571410
TI  - Advances in imaging in the postoperative patient with a rising prostate-specific
      antigen level.
AB  - Imaging prostate cancer continues to represent a clinical challenge for both
      primary and recurrent disease. In the evaluation of the
      persistent/recurrent/metastatic prostate cancer, knowledge of cancer location
      (local v distant), size, and extent are essential in order to design a treatment,
      tailored to each patient's needs. There are evidence-based guidelines for the use
      of imaging in assessing the presence of distant spread of prostate cancer.
      Radionuclide bone scans and computed tomography (CT), magnetic resonance imaging
      (MRI), and/or positron emission tomography (PET) supplement clinical and
      biochemical evaluations (prostate-specific antigen [PSA]) for suspected
      metastatic disease to bones and lymph nodes. There is no consensus about the use
      of imaging in the evaluation of local tumor recurrence. The use of ultrasound has
      been limited to biopsy guidance of the prostatic bed, or percutaneous biopsy of
      enlarged lymph nodes detected on CT or MRI. The use of MRI is evolving. Recent
      studies indicate that the use of MRI provides valuable information in the
      evaluation of local tumor recurrence, and nodal and bony metastases. In a patient
      post-radiation therapy, the method of combining MRI anatomic information with MR
      spectroscopic metabolic information is evolving. Another modality offering
      information about anatomy and metabolism of the local disease is PET/CT. The
      value of PET/CT at present is controversial, but new studies exploring the role
      of PET/CT in aggressive prostate cancer are promising.

PMID- 14571411
TI  - Genome-wide gene expression analysis of prostate carcinoma.
AB  - Advances in our knowledge of the molecular basis of prostate cancer have the
      potential to improve patient care and outcome. The investigative pace has
      recently been dramatically enhanced by the availability of the complete human
      genome sequence and the development of high-throughput technology for
      comprehensive genetic analysis. The application of genomic scale analysis to the
      study of prostate cancer has resulted in significant successes, including methods
      of more precise diagnosis and identification of potential prognostic markers and
      therapeutic targets. It is clear that these novel technologies and approaches
      provide many opportunities for biologists and clinicians; however, there are many
      challenges in moving these discoveries forward.

PMID- 14571412
TI  - Immunotherapy for prostate cancer.
AB  - While androgen deprivation has remained the cornerstone of therapy for advanced
      prostate cancer over the last 60 years, novel therapies are being developed that
      may expand upon currently available treatments. The identification of antigens
      expressed by prostate tissue and/or prostate cancer that are recognized by T
      cells creates opportunities to develop novel immunotherapeutic approaches,
      including tumor vaccines. Improved understanding of immune recognition and
      antigen presentation may lead to effective immunotherapies for prostate cancer.
      Identified proteins expressed in prostate cancer, including prostate-specific
      antigen (PSA), prostatic acid phosphatase (PAP), and prostate-specific membrane
      antigen (PSMA), have been used as immunologic targets for immunotherapy.
      Moreover, innovations in cancer genomics and proteomics will also aid in the
      identification of immunologic targets. Immunotherapy trials have already
      demonstrated evidence of not only immunogenicity, but also clinical efficacy, and
      future studies will be directed at capitalizing on these findings.

PMID- 14571413
TI  - DNA vaccines: an active immunization strategy for prostate cancer.
AB  - Immunotherapy is currently being investigated as a treatment for patients with
      asymptomatic, recurrent prostate cancer manifested only by a rising prostate
      specific antigen (PSA) level. Several different approaches to active immunization
      against antigens found on cancer cells have been explored. Immunization with DNA
      overcomes many of the obstacles noted in previous studies. Injection of plasmid
      DNA encoding a xenogeneic differentiation antigen (prostate-specific membrane
      antigen [PSMA]) is a potent means to induce antibody and T-cell responses to
      these otherwise poorly immunogenic self proteins. Use of the xenogeneic DNA (ie,
      human PSMA DNA injected into mouse) has been shown to be an absolute requirement
      to overcome immunologic tolerance. We are currently conducting a phase I trial of
      human and mouse PSMA DNA vaccines in patients with recurrent prostate cancer,
      based on preclinical experiments described below.

PMID- 14571414
TI  - Targeted systemic therapy of prostate cancer with a monoclonal antibody to
      prostate-specific membrane antigen.
AB  - For the last 60 years, hormonal therapy has been the cornerstone of treatment of
      metastatic prostate cancer. Unfortunately, hormonal therapy is purely palliative
      and improved systemic therapies are necessary. Monoclonal antibodies (mAbs) have
      proven valuable in the treatment of several diseases including cancer. mAbs act
      by focusing an immune response on or by targeting delivery of highly cytotoxic
      agents to the cancer cells without targeting normal cells. Prostate-specific
      membrane antigen (PSMA) has been identified as an ideal antigenic target in
      prostate cancer. PSMA is the most well-established, highly restricted prostate
      cancer cell surface antigen. It is expressed at high density on the cell membrane
      of all prostate cancers, and after antibody binding, the PSMA-antibody complex is
      rapidly internalized along with any payload carried by the antibody. J591 is the
      first IgG mAb developed to target the extracellular domain of PSMA, and it has
      been deimmunized (humanized) to allow repeated dosing in patients. Three phase I
      studies are in progress, two using the beta-emitting radiometals yttrium 90 and
      lutetium 177, and a third using a cytotoxin (DM1) linked to J591. Imaging of
      patients after they have received radiolabeled J591 demonstrates excellent tumor
      targeting.

PMID- 14571415
TI  - Endothelin receptor antagonists in the treatment of prostate cancer.
AB  - The endothelin (ET) axis represents a novel and exciting target in the treatment
      of prostate cancer. ET-1, acting primarily through the endothelin A receptor
      (ET(A)), is integrally involved in multiple facets of prostate cancer
      progression, including cell growth, inhibition of apoptosis, angiogenesis,
      development and progression of bone metastases, and mediation of pain responses.
      Clinical trials with the ET(A) antagonist, atrasentan, have demonstrated good
      tolerability, with the most common adverse events being headache, rhinitis, and
      peripheral edema. These trials have demonstrated statistically significant
      improvements in pain measures, prostate-specific antigen (PSA) kinetics, biologic
      markers of bone changes, and development of bone metastases. There have also been
      consistent improvements in time to progression, although not always statistically
      significant. Ongoing studies in a variety of patient populations will better
      define the role of ET receptor antagonists in the treatment of men with prostate
      cancer. In this article, we review the biology and pathophysiology of the ET axis
      in prostate cancer, critically analyze the major clinical trials reported to
      date, and discuss some emerging data and how it may impact the way we proceed in
      the future with the development of this class of drugs in prostate cancer.

PMID- 14571416
TI  - The development of differentiation agents for the treatment of prostate cancer.
AB  - Given their novel mechanisms of action and relatively favorable toxicity
      profiles, differentiation agents have been the focus of much investigation in the
      field of oncology. Among the most well studied of these agents in prostate cancer
      have been the retinoids, vitamin D, peroxisome-proliferator-activated receptor
      gamma (PPARgamma) ligands, and, most recently, the histone deacetylase (HDAC)
      inhibitors. While the clinical activity of these agents has been limited, several
      obstacles to the development of these novel drugs have become apparent. A lack of
      validated measures of outcome and uncertainty regarding the appropriate disease
      states in which to test these agents have led to difficulty in trial design.
      Furthermore, a better understanding of the biologic targets and genes manipulated
      by these therapies is required such that more potent and selective drugs may be
      developed. By overcoming these obstacles, the full potential of this therapeutic
      class may be realized.

PMID- 14571417
TI  - Differentiating agents and the treatment of prostate cancer: Vitamin D3 and
      peroxisome proliferator-activated receptor gamma ligands.
AB  - Much interest has developed recently in the use of differentiating agents in the
      management of solid tumors, specifically prostate cancer. Two classes of drugs
      that have shown particularly intriguing results are vitamin D(3) and its analogs
      and the peroxisome proliferator-activated receptor gamma (PPARgamma) ligands.
      Both the vitamin D(3) receptor and the PPARs are members of the nuclear receptor
      superfamily of ligand-dependent transcription factors and both are widely
      expressed by prostate cancer cells. This article reviews in detail the
      preclinical and clinical data available supporting the use of these agents in the
      treatment of prostate cancer. The proposed mechanisms of action of these agents
      and potential future therapeutic roles for these drugs are discussed as well.

PMID- 14571418
TI  - Hsp90 as a therapeutic target in prostate cancer.
AB  - Prostate cancers are hormone-dependent malignancies that respond to drugs that
      reduce circulating testosterone levels or prevent binding of this ligand to the
      androgen receptor (AR). While effective, these approaches are not curative and,
      in almost all cases, progression to a castration-resistant state is eventually
      observed. The mechanisms underlying the development of hormone resistance are
      poorly defined but several molecular changes are commonly associated with this
      process. Since a common element of these resistance mechanisms is restoration of
      AR signaling, agents that target AR expression represent an attractive treatment
      option for prostate cancer patients with disease progression following
      castration. Prior to ligand binding, AR exists in a complex with heat shock
      protein 90 (Hsp90) and other co-chaperones. The AR-Hsp90 interaction maintains AR
      in a high-affinity ligand-binding conformation, which is necessary for efficient
      response to hormone. 17-Allyamino-17-demethoxygeldanamycin (17-AAG) is an
      inhibitor of the Hsp90 chaperone protein. Inhibition of Hsp90 function causes the
      proteasomal degradation of proteins that require this chaperone for maturation or
      stability. Hsp90 clients include several proteins of potential importance in
      mediating prostate cancer progression, including wild-type and mutated AR, HER2,
      and Akt. In murine models of prostate cancer, 17-AAG causes the degradation of
      these client proteins at nontoxic doses and inhibits the growth of hormone-naive
      and castration-resistant tumors. These data suggest that inhibitors of Hsp90 may
      represent a novel strategy for the treatment of patients with prostate cancer and
      clinical trials to test this hypothesis are currently ongoing.

PMID- 14571427
TI  - Thread-like bridging strands: a morphologic feature present in all adenomatoid
      tumors.
AB  - Adenomatoid tumor (AT) is a benign, relatively rare neoplasm occurring primarily
      in the genital tract of both genders. Histologically, ATs were composed of
      fibrous tissue, which are separated by numerous slit-like and pseudotubular
      spaces. Peculiar "thread-like bridging strands" (TBS) crossing the pseudotubular
      spaces are typical morphologic feature. In this study, the frequency of
      occurrence of these TBS within a large series of ATs in various organs was
      examined. Sixty-nine cases were included in our study. Twenty-eight cases
      occurred in women, 41 cases in men. Tumors were located in the myometrium,
      fallopian tube, ovary, epididymis, tunica albuginea, and testicular parenchyma.
      Tumor size ranged from 0.8 to 8.2 cm (mean, 2.7 cm). TBS were found in 100% of
      cases. Presence of thin intraluminal TBS within ATs was a constant morphologic
      feature independently on gender and localization of the lesions.
      Ultrastructurally, they were always formed by apposition of attenuated cytoplasm
      of two adjacent mesothelial cells. In our opinion, TBS are morphologically very
      specific for ATs and we are not aware of any other epithelial structure in any
      organ demonstrating as appearance similar to these TBS of ATs.

PMID- 14571419
TI  - Role of bisphosphonates in prostate cancer bone metastases.
AB  - Bisphosphonate inhibitors of bone resorption have a variety of positive actions
      against prostate cancer cells in vitro and in preclinical animal models. In
      patients, they can reduce skeletal-related events and bone pain, as well as
      reduce the adverse effects of androgen deprivation therapy on skeletal integrity.
      The preclinical and clinical data to support this are reviewed here. Further
      clinical trials are required to determine whether bisphosphonates decrease tumor
      burden or increase patient survival or quality of life, and whether such adjuvant
      treatments will be cost-effective.

PMID- 14571428
TI  - Comparative immunoprofile of polymorphous low-grade adenocarcinoma and
      canalicular adenoma.
AB  - Immunohistochemistry is an important tool when dealing with salivary gland
      neoplasms. Canalicular adenoma and polymorphous low-grade adenocarcinoma may
      share some histologic characteristics that can cause difficulties in their
      separation. In the present study, cases of polymorphous low-grade adenocarcinoma
      and canalicular adenoma were submitted to a panel of antibodies to evaluate the
      differences in their immunoprofiles. The results obtained showed that, while
      vimentin is only expressed by polymorphous low-grade adenocarcinoma, CK7 and CK8
      are present in both neoplasms. Therefore, vimentin is the best marker to
      differentiate between these tumors.

PMID- 14571429
TI  - Expression of c-erbB-2 and cytokeratins 7 and 20 in urothelial carcinoma with
      gland-like lumina.
AB  - Urothelial carcinoma with gland-like lumina is an uncommon type of tumor,
      reported only occasionally in literature. Its diagnosis usually does not offer
      any difficulties, and its prognosis is determined by the accompanying classic
      transitional or squamous component. It is important though, not to misdiagnose it
      as a mixed transitional cell adenocarcinoma. In that respect, features such as
      the type of epithelium lining, the gland-like structures, as well as the type of
      luminal mucin have been used to make the diagnosis. Recently, an
      immunohistochemical panel of antibodies has proven helpful in differentiating
      primary and metastatic adenocarcinomas of urothelial tract from urothelial
      carcinoma with gland differentiation. In their series of 16 cases, Tamboli et al
      included only one case of transitional cell carcinoma with gland differentiation.
      We present two additional cases of urothelial carcinoma with gland-like lumina in
      two men, 60 and 79 years old, respectively. Both tumors were grade 2 of Ash
      Bergkvist, and the stage was pT(1) in both cases. Immunohistochemical study with
      cytokeratins 7 and 20, and with c-erbB-2, was performed. Both tumors expressed
      cytokeratins 7 and 20; c-erbB-2 was only expressed in one, in spite of the same
      staging. Although some relation has been found in animals between gland-like
      lumina phenotype and expression of epidermal growth factor (the receptor of which
      is homologous to c-erbB-2), it seems that this relationship might not be constant
      in humans.

PMID- 14571430
TI  - Cystic schwannoma of the pancreas.
AB  - Intrapancreatic schwannoma is a rare neoplasm. We report a case of a 46-year-old
      man with a cystic schwannoma in the head of the pancreas. This tumor, based on
      clinical manifestations and radiologic features, was initially suspected to be a
      cystic mucinous tumor of the pancreas or a pseudocyst. Histologically, the tumor
      was a typical schwannoma with cyst formation caused by degenerative changes.
      Immunostaining showed the tumor cells to be strongly and diffusely positive for S
      100 protein, vimentin, and CD56, and negative for cytokeratin AE1/AE3, desmin,
      smooth muscle myosin specific, CD34, and CD117, which support the diagnosis of
      schwannoma. Cystic schwannoma is a rare neoplasm occurring in the pancreas and
      should be considered in the differential diagnoses for patients presenting with
      pancreatic cystic lesions.

PMID- 14571431
TI  - Basal cell adenoma-an unusual presentation.
AB  - Basal cell adenoma is an uncommon epithelial neoplasm of the salivary gland most
      commonly arising in the parotid glands. We report a case of basal cell adenoma of
      the minor salivary gland presenting as a slowly progressing, large parapharyngeal
      mass. Histopathology revealed a well-encapsulated mass with characteristic
      histomorphology. Immunohistochemistry showed selective positivity for
      pancytokeratin, S-100, and smooth muscle actin in the tumor which highlighted the
      participation of myoepithelial cells in histogenesis. In addition, positivity was
      noted for carcinoembryonic antigen and vimentin. Ultrastructural analysis showed
      characteristic features including reduplicated basal laminae around the tumor
      cells, presence of intermediary filaments, and rough endoplasmic reticulum in the
      cytoplasm. There are no reports of basal cell adenoma presenting as a
      parapharyngeal mass lesion in the available English literature. This case
      highlights the rarity of this tumor with regard to its site of origin, possibly
      from a minor salivary gland.

PMID- 14571432
TI  - Chromophobe renal cell carcinoma with sarcomatoid transformation.
AB  - We present a rare case of a chromophobe renal cell carcinoma that progressed to a
      high-grade spindle cell sarcoma. The tumor affected a 50-year-old man who had
      presented with right upper quadrant discomfort and hematuria and subsequently
      underwent a right radical nephrectomy. Microscopically, the tumor was composed of
      two distinct components, a chromophobe renal cell carcinoma and a sarcomatoid
      component. The sarcomatoid component had exhibited aggressive behavior by
      spreading to a regional lymph node. This case report shows that chromophobe
      carcinoma can develop a sarcomatoid transformation with a high propensity for
      invasive growth and metastasis.

PMID- 14571433
TI  - Ovarian yolk sac tumor associated with endometrioid carcinoma and mucinous
      cystadenoma of the ovary.
AB  - The clinicopathologic and immunohistochemical findings of an unusual case of
      ovarian yolk sac tumor associated with endometrioid carcinoma and mucinous
      cystadenoma of the ovary are reported. The tumor was detected in a 51-year-old
      postmenopausal woman who presented with abdominal swelling and a pelvic mass. The
      patient underwent total abdominal hysterectomy with bilateral salpingo
      oophorectomy and omentectomy. The tumor was confined to the right ovary and
      measured 16.0 cm in greatest dimension. Microscopic examination revealed that the
      tumor had a yolk sac component associated with an endometrioid carcinoma, grade
      I, and a mucinous cystadenoma. A background of atypical endometriosis was noted.
      Immunoperoxidase studies showed that the yolk sac component stained diffusely
      with a cytokeratin cocktail and was focally positive for alpha-fetoprotein. It
      was negative for keratin 7. In contrast, the endometrioid carcinoma stained
      positive for keratin 7 in addition to the cytokeratin cocktail, but was negative
      for alpha-fetoprotein. After surgery, the patient received three cycles of
      chemotherapy. However, the disease progressed and the patient died 10 months
      after the diagnosis of the ovarian tumor.

PMID- 14571434
TI  - Colic metastases of alveolar soft-part sarcoma: a case report and review of the
      literature.
AB  - Alveolar soft-part sarcoma is a rare soft tissue malignant tumor that commonly
      arises in skeletal muscles or musculofascial planes in children and young adults.
      Metastases of lung, brain, and bone are often present at the time of diagnosis or
      appear late in the course of disease. We present the first case, to our
      knowledge, of colic metastases in a 43-year-old woman who had a leg primary tumor
      more than 15 years ago and multiple lung and brain metastases. The treatment of
      these two caecal metastases, revealed by an anemia, consisted in laparoscopic
      right colectomy.

PMID- 14571435
TI  - Emperipolesis in a case of B-cell lymphoma: a rare phenomenon outside of Rosai
      Dorfman disease.
AB  - We describe a case of a diffuse large B-cell lymphoma with extensive
      emperipolesis phenomenon. Light microscopy revealed numerous CD68-positive/S-100
      negative histiocytes containing viable neoplastic hematopoietic cells in their
      cytoplasm. Electron microscopy confirmed these findings. In this case, there was
      no evidence of Rosai-Dorfman disease either clinically or histologically. This
      report emphasizes that emperipolesis is not restricted to Rosai-Dorfman disease
      and can be found in other conditions including non-Hodgkin lymphomas.

PMID- 14571436
TI  - A case of juxtaglomerular cell tumor associated with membranous
      glomerulonephritis.
AB  - The association of membranous glomerulonephritis with benign tumors is rarely
      described. This report represents, to the best of our knowledge, the first
      documented account of the simultaneous occurrence of juxtaglomerular cell tumor
      of the kidney and membranous glomerulonephritis. A young Chinese woman presented
      with hypertension and proteinuria, whereupon investigations disclosed a renal
      tumor. She underwent surgical resection, and histologic examination of the tumor
      revealed CD34-positive uniform polygonal cells with accompanying mast cells,
      disposed in sheets with focal papillary pattern punctuated by cytokeratin
      positive tubular structures. Characteristic rhomboid crystalline granules were
      identified ultrastructurally. The kidney adjacent to the tumor showed features of
      membranous glomerulonephritis and hypertensive arteriopathy. Proteinuria improved
      following tumor resection, but the patient had persistent hypertension
      attributable to renal hypertensive arteriopathy. This report also highlights the
      recently described observation of CD34 positivity in juxtaglomerular cell tumors.

PMID- 14571438
TI  - Thomas Hodgkin.

PMID- 14571437
TI  - Current controversies regarding the role of asbestos exposure in the causation of
      malignant mesothelioma: the need for an evidence-based approach to develop
      medicolegal guidelines.
AB  - Asbestos is a group of fibrous silicate minerals that includes two mineralogic
      groups: amphiboles and serpentines. While the carcinogenic role of amphiboles
      (eg, crocidolite and amosite) is well established, medical "experts" that tend to
      strongly advocate their views currently argue in medicolegal cases multiple
      specific issues regarding the carcinogenicity of asbestos fibers. For example, it
      is controversial whether chrysotile causes malignant mesothelioma (MM); what are
      the specific carcinogenic thresholds for amphiboles and chrysotile; what
      occupations are truly at risk to develop MM as a result of asbestos exposure;
      what is the role of chrysotile in the development of peritoneal MM; how to assign
      causation in individuals exposed to multiple industrial products containing
      variable concentrations of various asbestos fibers; and, what criteria should be
      used to accept causation in household exposure cases and others. The causation
      criteria currently acceptable in U.S. courts are surprisingly flexible and
      subject to variable interpretation by medical "experts." At a time where
      thousands of individuals are claiming causation of MM by asbestos exposure, there
      is a need to develop more specific causation guidelines based on scientific
      evidence. Evidence-based medicine has been proposed as a new approach to the
      study, teaching, and the practice of medicine and has been used as a process of
      systematically reviewing the relevant studies in the literature to assess their
      scientific validity and development of guidelines. This article summarizes some
      of the current controversies regarding the role of asbestos exposure in the
      causation of MM and suggests the need for future evidence-based medicine-type
      studies to develop causation guidelines that could be used consistently during
      litigation.

PMID- 14571439
TI  - Immunoreactivity of ductal cells with putative myoepithelial markers: a potential
      pitfall in breast carcinoma.

PMID- 14571444
TI  - Dosimetry for laser sulcular debridement.

PMID- 14571445
TI  - Imaging tissue response to electrical and photothermal stimulation with nanometer
      sensitivity.
AB  - BACKGROUND AND OBJECTIVES: Tissue response to thermal, electrical, or chemical
      stimuli are important in the health and survival of tissue. We report
      experimental results to assess tissue response to various stimuli using a low
      coherence differential phase interferometer. STUDY DESIGN/MATERIALS AND METHODS:
      The optical system utilized to measure tissue response is a novel fiber-based
      phase sensitive optical low coherence reflectometer (PS-OLCR). Inasmuch as the PS
      OLCR works with back-reflected light, noninvasive sensing of tissue response to
      stimuli is possible. In addition to high lateral (approximately 10 microm) and
      longitudinal (approximately 10 microm) resolution, PS-OLCR can measure sub
      wavelength changes in optical path-length (Angstrom/nanometer range) by
      extracting the phase difference between interference fringes in two channels
      corresponding to orthogonal polarization modes. RESULTS: When light spatially
      splits into two polarization states, precise analysis of surface topography or
      tissue surface response such as swelling or collapse are possible. Time resolved
      measurements of nanometer-scale path length changes in response to electrical and
      thermal stimuli are demonstrated using longitudinally delayed polarization
      channels. CONCLUSIONS: Since PS-OLCR is a useful tool to detect ultra-small path
      length changes, the system has potential to aid scientists in investigating
      important phenomena in biomaterials and developing useful diagnostic and
      therapeutic imaging modalities. Applications include tissue surface profilometry,
      measurement of tissue, and cell response to various stimuli, high-resolution
      intensity and phase imaging.

PMID- 14571446
TI  - Effects of dehydration on the optical properties of in vitro porcine liver.
AB  - BACKGROUND AND OBJECTIVES: It is of crucial importance to determine the effects
      of dehydration on the optical properties of tissue so that optimization of
      therapy and device for laser applications in medicine can be made. STUDY
      DESIGN/MATERIALS AND METHODS: After being incubated directly or indirectly in an
      oven of 37 degrees C for different periods of time, the porcine liver samples
      were weighed with an electronic scale and their optical properties were measured
      by a double integrating sphere system. RESULTS: When samples were incubated
      directly for 20 hours, the average weight loss was 68.5% +/- 1.2%, and the
      absorption coefficient and scattering coefficient increased 146.1% +/- 26.9% and
      10.8% +/- 1.1%, respectively. In comparison, there was only 21.5% +/- 1.0% of
      water loss for the control samples, and the absorption coefficient increased
      30.7% +/- 7.6%, while the reduced scattering coefficient increased 386.5% +/-
      29.7%. The effective attenuation coefficients increased 111% and 103% for
      dehydration group and control group, respectively. CONCLUSIONS: The absorption
      coefficient and effective attenuation coefficient increase with dehydration level
      of tissue. However, there is no direct correlation between dehydration and
      reduced scattering coefficient.

PMID- 14571447
TI  - Multicenter study of noninvasive radiofrequency for periorbital tissue
      tightening.
AB  - BACKGROUND AND OBJECTIVES: This 6-month study evaluated the efficacy and safety
      of treatment with a nonablative radiofrequency (RF) device. STUDY
      DESIGN/MATERIALS AND METHODS: Eighty-six subjects received a single treatment
      with the ThermaCool TC System (Thermage, Inc., Hayward, CA) and were evaluated
      for 6 months after treatment. RESULTS: Independent scoring of blinded photographs
      resulted in Fitzpatrick wrinkle score improvements of at least 1 point in 83.2%
      (99/119) of treated periorbital areas. Treating physicians, without reference to
      pre-treatment photographs, noted improvements in 28.9% (48/166) of treatment
      areas. Fifty percent (41/82) of subjects reported being satisfied or very
      satisfied with periorbital wrinkle reductions. Objective photographic analysis
      showed that 61.5% (40/65) of eyebrows were lifted by at least 0.5 mm. Rates and
      duration of edema/erythema were very low (e.g., vs. ablative procedures). Overall
      2nd-degree burn incidence was 0.36% (21 per 5,858 RF applications). Three
      patients had small areas of residual scarring at 6 months. CONCLUSIONS: A single
      treatment with this RF tissue tightening (RFTT) device produces objective and
      subjective reductions in periorbital wrinkles, measurable changes in brow
      position, and acceptable epidermal safety. These changes were indicative of a
      thermally induced early tissue-tightening effect followed by additional
      tightening over a time course consistent with a thermal wound healing response.

PMID- 14571448
TI  - In vitro effects of pulsed holmium laser energy on canine uroliths and porcine
      cadaveric urethra.
AB  - BACKGROUND AND OBJECTIVES: To assess the effect of holmium laser energy on canine
      uroliths and porcine urethra. STUDY DESIGN/MATERIALS AND METHODS: Uroliths of
      known composition and fresh cadaveric urethra were exposed to holmium laser
      energy. Urolith fragmentation times and depth of urethral lesions were
      determined. RESULTS: Overall mean fragmentation time was 11.8 +/- 8.01 seconds.
      Magnesium ammonium phosphate (MAP) and urate uroliths had significantly shorter
      fragmentation times compared to other uroliths. Fragmentation time of MAP
      uroliths irradiated with 1.2 J/pulse was significantly longer than the
      fragmentation time of MAP uroliths irradiated with 0.3 J/pulse. Overall mean
      lesion depth for urethral specimens treated with 90 degrees contact mode
      irradiation was significantly greater than overall mean lesion depth for
      specimens treated with 30 degrees non-contact mode. CONCLUSIONS: Holmium laser
      energy effectively fragmented canine uroliths and caused minimal urethral damage
      in vitro. Dogs with urolithiasis may represent a useful animal model for
      developing human lithotripsy procedures.

PMID- 14571450
TI  - Effects of Er:YAG and Nd:YAG laser irradiation on radicular dentine permeability
      using different irrigating solutions.
AB  - BACKGROUND AND OBJECTIVES: To evaluate the effect of Er:YAG and Nd:YAG laser on
      radicular dentine permeability when using distilled and deionized water and 1%
      NaClO as irrigating solutions. STUDY DESIGN/MATERIALS AND METHODS: Thirty human
      maxillary canines were divided randomly into six groups. The root canals were
      instrumented with K files and the step-back technique. Group I, irrigation with
      distilled and deionized water; Group II, irrigation with 1% NaClO; Group III,
      irrigation with distilled and deionized water and Er:YAG laser application (140
      mJ input, 61 mJ output 15 Hz, 300 pulses, and 42 J); Group IV, irrigation with 1%
      NaClO and Er:YAG laser application (same parameters as Group III); Group V,
      irrigation with distilled and deionized water and Nd:YAG laser application (150
      mJ, 15 Hz, 2,25 W); Group VI, irrigation with 1% NaClO and Nd:YAG laser
      application (same parameters as Group V). During laser application the teeth were
      always filled with the irrigating solution. The tip was withdrawn gently in
      helicoidal movement from the apex to the cervical portion. The teeth were
      processed for histochemical evaluation. RESULTS: The Tukey test showed that the
      cervical and middle thirds were statistically similar (P > 0.05) and
      significantly greater than the apical third (P < 0.05). The Scheffe test showed
      significantly greater dentine permeability in root canals in which water and
      Er:YAG laser were used and were significantly different from the other treatments
      (P < 0.05). CONCLUSIONS: The use of distilled and deionized water and Er:YAG
      laser showed the greater increase of dentine permeability. The use of 1% NaClO
      with Nd:YAG laser, distilled, and deionized water with Nd:YAG laser and the use
      of water increased dentine permeability less than the other groups. The use of 1%
      NaClO with and without Er:YAG laser application were positioned intermediately
      among the treatments.

PMID- 14571449
TI  - Experimental evaluation of possible side effects of intra-operative photodynamic
      therapy on rabbit blood vessels and nerves.
AB  - BACKGROUND AND OBJECTIVES: Tumours of the head and neck show a high local tumour
      recurrence rate ranging between 7 and 30% despite combined treatment modalities.
      To improve these data, photodynamic therapy (PDT) might be used as an additional
      treatment besides surgery and radio-chemotherapy. Intra-operative PDT has been
      proposed to "sterilise" the tumour bed after surgical tumour resection in order
      to kill any remaining tumour cells which are responsible for local tumour
      recurrences. Often, during head and neck surgery, large blood vessels and
      important nerve structures are exposed and could potentially be harmed by intra
      operative PDT. Despite the fact that mTHPC is the most commonly used
      photosensitiser for head and neck tumours, there are no data on potential
      detrimental side effects of intra-operative PDT onto these vital structures. The
      purpose of this study was to use a maximal treatment protocol in rabbit observing
      possible damage to the blood vessels and nerve structures and thus judge the most
      severe event that could happen in patients. STUDY DESIGN/MATERIALS AND METHODS:
      In rabbits the large blood vessels and nerve structures at the neck and at the
      groin area were surgically exposed and treated by mTHPC-mediated intra-operative
      PDT. Various treatment parameters (drug-light interval, light dosage, follow up
      interval) were modified in order to find the critical treatment parameters which
      might cause maximum tissue effects. The intention was to define the most severe
      clinical complications which could be expected from mTHPC mediated intra
      operative PDT. RESULTS: The most severe tissue reactions were found at a drug
      dosage of 0.3 mg/kg, a drug-light interval of 24 hours and a light dosage of 20
      J/cm(2). Complete necrosis was found for the muscles, fat and connective tissue
      within the entire treatment field. Blood vessels demonstrated severe oedema,
      media-hyperplasia or loosening of the endothelial layer leading to various
      degrees of local thrombosis but no break down of the vessel wall or any rupture
      was noted. Most nerves were altered by a 75% demyelisation but this did not
      result in any clinical symptoms. CONCLUSIONS: Our results have shown that mTHPC
      mediated intra-operative PDT used with a maximal treatment protocol (very high
      doses and very short drug-light intervals) has significant histological impact
      onto all tissue structures, but did not show any clinical symptoms in rabbits.
      mTHPC mediated intra-operative PDT seems to be a promising and a safe treatment
      option which could complement existing treatment modalities in order to improve
      total survival rate of tumour patients.

PMID- 14571451
TI  - Increase of enamel fluoride retention by low fluence argon laser in vivo.
AB  - BACKGROUND AND OBJECTIVES: The aim of this in vivo study was to investigate if
      argon laser irradiation of enamel can increase the retention of fluoride. STUDY
      DESIGN/MATERIALS AND METHODS: Ninety-eight teeth in 12 patients were randomly
      divided into three groups: (1) EF group: 40 teeth were only treated by fluoride
      gel (application for 5 minutes followed by 1 minute rinsing with distilled
      water). (2) EFL group: 40 teeth were treated the same way as in the EF group but
      they were lased after fluoridation. (3) E group of 18 teeth were kept without any
      treatment and considered as reference. In order to quantify the fluoride content
      in the enamel samples, the teeth were analyzed by proton beam delivered by a
      tandem accelerator (PIgammaE, particle induced gamma-ray emission). The fluoride
      content of enamel surface is not homogeneous. Therefore, it is necessary to
      analyze the same enamel area after each treatment. Each tooth was maintained in a
      fixed tooth holder which was designed to analyze the tooth enamel surface at the
      same place (1 mm(2) and around 20 mum in depth) after various treatments. A low
      energy density of argon laser beam was used: 10.74 J/cm(2), 30 seconds of
      irradiation time and 340 m W of output power. RESULTS: The results after 7 days
      showed that the lased enamel still retained 157.4 +/- 23.371 ppm or 42.29% of
      fluoride after fluoridation process whereas the unlased enamel retained 45.59 +/-
      9.377 ppm or 12.25% of fluoride. CONCLUSIONS: We concluded that the use of argon
      laser at low energy density (10.74 J/cm(2)) significantly increases the fluoride
      retention in lased enamel which had approximately three times more fluoride than
      the unlased enamel.

PMID- 14571452
TI  - Influence of an optically thick water layer on the bond-strength of composite
      resin to dental enamel after IR laser ablation.
AB  - BACKGROUND AND OBJECTIVES: Several studies of hard tissue ablation with Er:YAG
      lasers have shown that the addition of an optically thick water layer (
      approximately 1 mm) added to the surface of dental enamel before each incident
      laser pulse, profoundly influences the rate and efficiency of ablation and the
      resulting surface morphology. The objective of this study was the determination
      of laser parameters which result in clinically useful bond strengths without the
      need for phosphoric acid etching. The hypothesis to be tested was that laser
      irradiation through a relatively thick layer of water would result in a surface
      to which composite could be bonded with bond strength similar to surfaces etched
      with phosphoric acid. This hypothesis is predicated on the assumption that the
      water prevents the formation of non-apatite calcium phosphate phases on the
      enamel surface. MATERIALS AND METHODS: In this study, a calibrated syringe pump
      and a motion control system were used to uniformly treat flat enamel surfaces
      using free-running Er:YAG laser pulses with and without water, and 9.6 mum CO(2)
      laser pulses on a dry surface for comparison. The rate of water delivery that
      resulted in the most efficient ablation was determined by profiling the resulting
      laser incisions using optical coherence tomography. In addition, enamel surfaces
      of 5 x 5 mm(2) were uniformly treated and the resulting surface morphology was
      examined using synchrotron radiation-fourier transform infrared spectroscopy (SR
      FTIR), and optical and electron microscopy. The influence of the modified surface
      morphology on the adhesion of composite resin was investigated. RESULTS: The
      shear-bond strength of composite bonded to enamel surfaces irradiated at
      intensities clinically relevant for caries removal approached values measured for
      conventional acid etching when the water delivery rate was optimized.
      CONCLUSIONS: This study demonstrates that composite restorative materials can be
      directly bonded to laser prepared surfaces without the necessity of further
      surface preparation and acid etching and that the addition of a thick water layer
      ( approximately 1 mm) prevents the formation of undesirable CaP phases that
      compromise adhesion to restorative materials. 2003.

PMID- 14571453
TI  - Edward H. Lambert.

PMID- 14571454
TI  - Peripheral nerve fascicles: anatomy and clinical relevance.
AB  - Within a peripheral nerve, the individual nerve fibers are grouped together in
      fascicles. Whether there is somatotopic organization within these fascicles has
      long been of interest, the subject of many investigations, and somewhat
      controversial. Evidence from diverse sources now points to important somatotopic
      clustering of nerve fibers within most of the length of the nerve. Information is
      lacking regarding proximal segments, particularly the plexus and spinal nerve
      root levels. As a result of this somatotopic arrangement, partial focal nerve
      lesions can produce restricted clinical deficits that defy the classic rules of
      localization. Examples of such restricted nerve lesions are provided in this
      review. Recognition of fascicle somatotopy is also important in the surgical
      approach to disorders of peripheral nerves.

PMID- 14571455
TI  - The peripheral nerve complications of human immunodeficiency virus (HIV)
      infection.
AB  - Peripheral nerve complications occurring in patients with human immunodeficiency
      virus (HIV) infection are frequent and challenging. This review discusses these
      various complications according to the degree of advancement of HIV disease.
      Particular emphasis is placed upon emerging causes of neuropathy found in the
      context of HIV disease, such as infection with hepatitis C and human T
      lymphotropic virus type I, as well as neuropathies related to antiretroviral
      medications.

PMID- 14571456
TI  - Positive salivary gland biopsy, Sjogren syndrome, and neuropathy: clinical
      implications.
AB  - The relationship between neuropathy and Sjogren syndrome has been predicated
      largely on sicca symptoms or serological abnormalities rather than salivary gland
      pathology. We reviewed consecutive neuropathy patients who had had a lip biopsy
      to identify features of the neuropathy that were associated with a positive lip
      biopsy suggesting Sjogren syndrome. Twenty of 54 neuropathy patients were biopsy
      positive; 13 had a painful or nonspecific sensory neuropathy and only 4 were
      ataxic. Sicca symptoms were not associated with a positive biopsy (P = 0.14).
      Serological abnormalities were found more often in the biopsy-positive group (P =
      0.008), but anti-Sjogren syndrome A or B (anti-SSA or SSB) antibodies were
      detected in only 30%. There were no other clinical or electromyographic (EMG)
      features associated with a positive biopsy. From this experience, we conclude
      that: (1). most patients with neuropathy and a positive lip biopsy for Sjogren
      syndrome have a painful, distal, sensory axonal neuropathy; (2). there are no
      clinical or EMG features that are predictive of a positive lip biopsy; (3).
      ataxic neuropathy is uncommon; and (4). the lack of sicca symptoms or anti-SSA or
      SSB antibodies in patients with neuropathy does not exclude Sjogren syndrome
      based upon salivary gland pathology.

PMID- 14571457
TI  - Acetylcholine receptor distribution and synapse elimination at the developing
      neuromuscular junction of mdx mice.
AB  - The pattern of innervation of the vertebrate neuromuscular junction is
      established during early development, when junctions go from multiple to single
      innervation in the phenomenon of synapse elimination, suggesting that changes at
      the molecular level in the postsynaptic cell lead to the removal of nerve
      terminals. The mdx mouse is deficient in dystrophin and associated proteins that
      are part of the postsynaptic cytoskeleton. We used rhodamine-alpha-bungarotoxin
      and anti-neurofilament IgG-FITC to stain acetylcholine receptors and nerve
      terminals of the sternomastoid muscle during postnatal development in mdx and
      control C57BL/10 mice. Using fluorescence confocal microscopy, we observed that,
      7 days after birth, 86.7% of the endplates of mdx mice were monoinnervated (n =
      200) compared with 41.4% in control mice (n = 200). By the end of the second
      postnatal week, all endplates were innervated singly (100% mdx and 94.7%
      controls, n = 200 per group). These results show that dystrophic fibers achieve
      single innervation earlier, perhaps because dystrophin or a normal cytoskeletal
      complex is implicated in this phenomenon.

PMID- 14571458
TI  - Clinical study of FK506 in patients with myasthenia gravis.
AB  - To investigate the usefulness of low-dose FK506 for the treatment of myasthenia
      gravis (MG), we treated 19 patients with generalized MG in a 16-week open
      clinical trial of FK506 (3-5 mg/day). At the end of the trial, total MG scores
      (range: 0-27 points) improved by 3 points or more in 7 of 19 patients (37%), and
      activities of daily living (ADL) scores (range: 0-6 points) also improved by 1
      point or more in 8 of 19 patients (42%). Nine of 19 patients (47%) showed
      improvement in either MG or ADL scores. Significant reduction of anti
      acetylcholine receptor antibody titers and interleukin 2 production were observed
      at the end of this study. Minor but commonly observed side effects were an
      increase in neutrophil count and a decrease in lymphocyte count. No serious
      adverse events such as renal toxicity or diabetes mellitus were observed during
      the 16-week treatment period. FK506 could safely serve as an adjunct to steroid
      therapy for MG at low dosage.

PMID- 14571459
TI  - Melas with point mutations involving tRNALeu (A3243G) and tRNAGlu(A14693g).
AB  - The syndrome of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like
      episode (MELAS) is typically associated with a single point mutation in the
      mitochondrial genome (mtDNA). Because mtDNA is known to have a higher mutation
      rate than nuclear DNA, we speculate that some patients with MELAS syndrome may
      harbor more than one mutation in mtDNA. For this purpose, mtDNA extracted from
      muscle containing dysmorphic mitochondria from a 32-year-old man with MELAS was
      sequenced in its entirety to identify all possible mutations. The result showed a
      homoplasmic A14693G and a heteroplasmic A3243G. The A14693G transition was not
      present in 205 unrelated control individuals, was not seen in 76 species randomly
      selected from GenBank, and appears to disrupt the base pairing within the T-loop
      of mtDNA tRNA(Glu). His asymptomatic siblings' blood showed wild-type at these
      positions, whereas the blood of the patient's oligosymptomatic diabetic mother
      had a heteroplasmic A14693G and an apparent homoplasmic wild-type A3243,
      suggesting an association of A14693G with diabetes mellitus. This case
      demonstrates the importance of sequencing the mtDNA in its entirety to evaluate
      the molecular basis of mitochondriopathy.

PMID- 14571460
TI  - Vasomotor dysfunction in carpal tunnel syndrome.
AB  - Little attention has been paid to small-fiber dysfunction in carpal tunnel
      syndrome (CTS) although its symptoms are common. This study investigates
      vasomotor dysfunction, which is controlled by small nerve fibers, in patients
      with CTS compared with control subjects. Vasomotor function was quantified by
      measuring, with laser Doppler velocimetry, skin vasoconstriction induced by a
      eutectic mixture of local anesthetic (EMLA) cream over digit tips 3, 4, and 5.
      Hands with CTS (n = 32) compared with controls (n = 19) demonstrated
      significantly reduced vasoconstriction in digits 3 and 4, but not digit 5. A
      blood flow ratio (digit 3/5) of less than 0.73 identified CTS in 69% with 68%
      specificity. Testing for vasomotor dysfunction in CTS allows for more
      comprehensive neurophysiological testing, which is heavily biased towards large
      nerve fibers.

PMID- 14571461
TI  - Differential responses of HSPs to heat stress in slow and fast regions of rat
      gastrocnemius muscle.
AB  - In a recent study, we showed that the rat slow soleus and fast plantaris muscles
      exhibited different time courses for the response of specific heat shock proteins
      (HSPs) after 1 h of heat stress. We hypothesized that these differential
      responses were related, in part, to the varying fiber type composition of these
      muscles. To further test this hypothesis, we now have determined the responses of
      Hsp60, Hsp72, and Hsc73 during the 60 h following exposure to a single bout of
      heat stress in the deep (relatively high percentage of slow fibers) and
      superficial regions (only fast fibers) of the adult rat gastrocnemius muscle. The
      temperature of the musculature in the left hindlimb was elevated to approximately
      42 degrees C for 1 h, while the right hindlimb served as a control. Two hours
      after the heat stress, the Hsp60 levels were increased by 1.3- and 2.0-fold in
      the deep and superficial regions, respectively. The Hsp72 levels were increased
      (1.8-fold) in the deep region at 8 h after heat stress, whereas in the
      superficial region these levels were increased between 4 and 48 h (peak at 36 h
      by 10-fold) after the heat stress. No changes were observed for Hsc73 in either
      region of the muscle. Combined with our previous data, the results indicate that
      the responses of HSPs in the rat hindlimb muscles after a single exposure to heat
      stress are related to fiber type composition of the muscle or muscle region or to
      the inherent properties of each HSP. From a clinical viewpoint, these data
      indicate that specific regions (most likely based on fiber type composition)
      within a muscle may be affected differentially by any intervention inducing HSPs.

PMID- 14571462
TI  - Autonomic and peripheral neuropathy in endstage liver disease and following liver
      transplantation.
AB  - Severe chronic liver disease may be associated with a peripheral somatic and an
      autonomic neuropathy. There are only a limited number of reports on the incidence
      and features of these neuropathies. In addition the effects of liver
      transplantation on these neuropathies have not been well studied. We examined
      peripheral somatic and autonomic nerve function in 42 patients with endstage
      liver disease prior to transplantation and also examined the effect of liver
      transplantation on these neuropathies in 14 patients. Peripheral somatic
      neuropathy (93%) and autonomic neuropathy (50%) were common in patients with
      endstage liver disease and were more frequent than previously reported.
      Abnormalities improved in some patients after liver transplantation, particularly
      if there was return of normal hepatic function.

PMID- 14571463
TI  - Strength training in older women: early and late changes in whole muscle and
      single cells.
AB  - In order to examine the relative contribution of neural- and muscle-based
      adaptation to strength training, we studied early (2 weeks) and later (12 weeks)
      effects of strength training on muscle size and strength and type I single-fiber
      size and contractility in 14 elderly women (aged 68-79 years) and seven young
      controls. Older subjects were randomized to training (n = 7) or control (n = 7)
      groups. Strength did not change, but whole muscle size increased significantly
      after 2 weeks. After 12 weeks, strength, whole muscle size, and specific force
      all increased. No changes occurred in the control group. In single fibers, no
      changes in size and contractility were noted after 2 weeks, but specific force
      was higher in the training group after 12 weeks. Early adaptations to strength
      training in elderly women cannot be attributed to changes at the cellular level
      and therefore occur primarily in the central nervous system. Later, cellular
      adaptations in specific force track closely whole muscle changes.

PMID- 14571464
TI  - Acute leg-cycling exercise attenuates the H-reflex recorded in soleus but not
      flexor carpi radialis.
AB  - The amplitude of the Hoffman reflex (H-reflex) in the soleus muscle is attenuated
      after acute bouts of leg-cycling exercise. The attenuation has been interpreted
      as a "tranquilizing" effect of exercise controlled by the central nervous system
      and generalized beyond a single spinal segmental level. If so, the postexercise
      depression of the H-reflex should occur in both the soleus and the flexor carpi
      radialis (FCR) muscle, which is not actively involved during leg cycling. This
      experiment examined the effect of moderate-intensity cycling exercise on the H
      reflex recorded in soleus and FCR among 16 men. The H-reflex was measured
      immediately before and 10 min after 30 min of either moderate-intensity leg
      cycling (60% VO(2peak)) or quiet rest. The acute bout of cycling exercise reduced
      the H-reflex in the soleus but not in the FCR. Thus, the attenuation of the H
      reflex after leg cycling does not generalize beyond the spinal segmental level
      that modulates the involved locomotory muscles; it is likely the result of
      segmental processes associated with the repetitive stretching or activation of
      the soleus muscle.

PMID- 14571465
TI  - Role of intertendinous connections in distribution of force in the human extensor
      digitorum muscle.
AB  - The human extensor digitorum (ED) muscle gives rise distally to multiple tendons
      that insert onto and extend digits 2-5. It has been shown previously that the
      spike-triggered average forces of motor units in ED are broadly distributed
      across many tendons. Such force dispersion may result from linkages between the
      distal tendons of ED and may limit the ability to move the fingers independently.
      The purpose of this study, therefore, was to determine the extent to which the
      connections between tendons of ED distribute force across the fingers.
      Stimulation of ED muscle fibers was performed at 107 different sites in four
      subjects. The isometric force exerted on digits 2-5 resulting from the
      stimulation was measured separately. Stimulus-triggered averaging of each of the
      four force channels yielded the force contribution to each of the digits due to
      the stimulation at each site. A selectivity index from 0 (a site that distributes
      force equally across the fingers) to 1.0 (a site that produces force on a single
      finger) was computed to describe the distribution of force across the four
      fingers. The selectivity index resulting from electrical stimulation of ED
      averaged 0.70 +/- 0.21. These selectivity index values were significantly greater
      (P < 0.001) than those obtained for single motor units using spike-triggered
      averaging. These findings suggest that linkages between the distal tendons of ED
      probably play only a minor role in distributing force across the fingers and,
      therefore, other factors must be primarily responsible for the inability to move
      the fingers independently.

PMID- 14571467
TI  - Occurrence of A-waves in F-wave studies of healthy nerves.
AB  - A-waves are compound muscle action potentials that follow the M-wave with a
      constant shape and latency; usually they are detected during F-wave studies. A
      large reference value database for F-wave parameters from the median, ulnar,
      peroneal, and tibial nerves was collected from 121-196 subjects aged 14 to 95
      years without known pathology involving the studied nerves. From this material,
      we studied retrospectively the occurrence of A-waves. To be included, an A-wave
      had to be clearly discriminated from the baseline in at least 8 of 20 traces with
      a jitter of less than 0.5 ms. A-waves occurred in 25% of the tibial nerves
      studied and 14% of the peroneal nerves but in only 2% of median and ulnar nerves.
      In the peroneal and tibial nerves, the frequency of A-waves increased with age,
      suggesting that A-waves may be related to normal age-related mild neuropathic
      changes of alpha motor neurons. Thus, A-waves are frequently found in lower
      extremity nerves in healthy subjects and less commonly in upper-extremity nerves.
      Their presence must therefore be interpreted with caution and cannot be taken as
      necessarily indicative of abnormality.

PMID- 14571466
TI  - X-linked motor and sensory neuropathy with pyramidal signs and cerebral white
      matter lesions.
AB  - We report two brothers with hereditary motor and sensory neuropathies and
      pyramidal signs. Electrophysiological evaluation revealed polyneuropathy and
      involvement of the central motor, somatosensory, and auditory pathways. Brain
      magnetic resonance imaging studies showed diffuse white matter lesions, and sural
      nerve biopsy identified a reduction in the large myelinated nerve fibers. The
      patients' mother and sister exhibited similar, but milder neurologic findings
      suggesting that the genetic defect may be X-linked; however, a point mutation in
      the connexin 32 gene was negative.

PMID- 14571468
TI  - Clinical and neurophysiological evaluation of progression in amyotrophic lateral
      sclerosis.
AB  - There is a need for a sensitive neurophysiological measure of disease progression
      in following the course of patients with amyotrophic lateral sclerosis (ALS). We
      studied two groups of nine ALS patients, one with slow progression (Group A) and
      the other with rapid progression (Group B). We evaluated muscle strength scores
      using the Medical Research Council (MRC) scale in limb and trunk muscles, forced
      vital capacity (FVC), and ALS functional rating scale (ALS-FRS) scores. Maximal
      voluntary isometric contraction (MVIC) of the abductor digiti minimi muscle (ADM)
      was measured, using a digital device. We also measured M-wave amplitude and area
      in the ADM, and the distal motor latency and F-wave frequency in the ulnar nerve;
      from these data, the neurophysiological index (NI) was calculated, as described
      previously. In both groups, the NI was the most sensitive measure of change, with
      the smallest coefficient of variation. We conclude that the NI, which requires no
      special technology and no new clinical or technical skills to use, is sensitive
      to change, and therefore may be useful in clinical trials, as well as in a
      clinical setting.

PMID- 14571469
TI  - Mononeuropathy multiplex in association with livedoid vasculitis.
AB  - Livedoid vasculitis is a chronic dermatological disorder associated with
      petechiae and recurrent, unusually shaped ulcers that heal to form
      hyperpigmentated areas and atrophie blanche. This condition is more correctly
      termed a vasculopathy, rather than a vascultis, and is often associated with an
      underlying hypercoagulable disorder. We report a patient with livedoid vasculitis
      and mononeuropathy multiplex. We propose that peripheral nervous system
      involvement arises from multifocal areas of ischemia due to fibrin and thrombin
      deposition within both the wall and lumen of vasa nervorum.

PMID- 14571470
TI  - McArdle's disease presenting as recurrent cryptogenic renal failure due to occult
      seizures.
AB  - Myophosphorylase deficiency (McArdle's disease) may present with episodic renal
      failure following exertion. We present a case of adult-onset myophosphorylase
      deficiency in which recurrent bouts of renal failure could not be associated with
      any exertional events until a tonic seizure was witnessed after the fourth
      episode of renal failure. In the absence of a clear exertional cause for
      myoglobinuria, an occult seizure disorder should be suspected.

PMID- 14571471
TI  - The piriformis syndrome is overdiagnosed.

PMID- 14571472
TI  - The piriformis syndrome is underdiagnosed.

PMID- 14571473
TI  - Accessory neuropathy after high-dose radiation therapy for tongue-base carcinoma.

PMID- 14571474
TI  - Low back pain.

PMID- 14571477
TI  - Renal angioplasty and stenting under protection: the way for the future?
AB  - The purpose of this study was to evaluate the feasibility and safety of renal
      artery angioplasty and stenting utilizing a distal protection device to reduce
      the risk of intraprocedural artery embolism and avoid deterioration of the renal
      function. Fifty-six hypertensive patients (32 men; mean age, 66 +/- 11.8 years;
      range, 22-87) with atherosclerotic renal artery stenosis (8 bilateral) underwent
      angioplasty and stenting with distal protection in 65 renal arteries (58 ostial
      lesions). Five patients had a solitary kidney, 18 a renal insufficiency. The
      lesion was crossed either with a GuardWire temporary occlusion balloon (n = 38),
      which was inflated to provide parenchyma protection or with a filter (EPI Filter;
      n = 26), or with Angioguard (n = 1), which allows a continuous flow. Generated
      debris was aspirated and analyzed. Blood pressure and serum creatinine levels
      were followed. Immediate technical success was 100%. All lesions except one were
      stented, either directly (43 ostial lesions) or after predilatation (22 ostial
      lesions). Visible debris were aspirated with the PercuSurge in all patients or
      removed with filters in 80% of the patients. Mean particle number and diameter
      were 98.1 +/- 60.0 per procedure (range, 13-208) and 201.0 +/- 76.0 microm
      (range, 38-6,206), respectively. Mean renal artery occlusion time was 6.55 +/-
      2.46 min (range, 2.29-13.21) with the PercuSurge device. Mean time in situ
      (filters) was 4.25 +/- 1.12 min. Mean follow-up was 22.6 +/- 17.6 months (range,
      1-47). Systolic and diastolic blood pressure declined from 169.0 +/- 15.2 and
      104.0 +/- 13.0 mm Hg, respectively, to 149.7 +/- 12.4 and 92.7 +/- 6.7 mm Hg
      after the procedure. The mean creatinine level remains constant during the follow
      up. At 6-month follow-up (45 patients), renal function did not deteriorate in any
      patient, whereas 8 patients with baseline renal insufficiency improved after the
      procedure. At 3 years (19 patients), renal function deteriorated only in 1
      patient with renal insufficiency and in 1 patient treated for bilateral renal
      stenosis, one side without protection. These preliminary results suggest the
      feasibility and safety of distal protection during renal interventions to protect
      against atheroembolism and to avoid renal function deterioration. This
      technique's beneficial effects should be evaluated by randomized studies.

PMID- 14571478
TI  - Safe angioplasty and the pregnant kidney?

PMID- 14571479
TI  - Simultaneous stenting of the carotid artery and other coronary or extracoronary
      arteries: does a combined procedure increase the risk of interventional therapy?
AB  - Simultaneous interventions in carotid and other extracarotid arteries are not
      performed on a routine basis up to now. In 67 out of 295 consecutive patients
      (23%) undergoing elective stenting of the internal carotid artery, additional
      interventions in the coronary arteries (n = 65), the iliac artery (n = 3), renal
      artery (n = 1), left subclavian artery (n = 3), vertebral artery (n = 4), or a
      combination thereof were performed. Primary stenting was done in 51 (74%) out of
      69 carotid arteries, in 48 (74%) of 65 coronary arteries, and in 10 (91%) of 11
      other targeted vessels. Neurological complications consisted of two (2.9%)
      transient ischemic attacks and one (1.5%) minor stroke. In addition, one (1.5%)
      myocardial infarction occurred during coronary artery intervention. In
      comparison, 16 (6.6%) transient ischemic attacks, 1 minor stroke (0.4%), 5 (2.2%)
      major strokes, and 3 (1.2%) deaths were observed in 228 patients without combined
      procedures. Simultaneous percutaneous interventions including carotid arteries
      and other extracarotid arteries are feasible, relatively safe, and cost
      effective.

PMID- 14571480
TI  - Endovascular intervention of aortoiliac occlusive disease in high-risk patients
      using the kissing stents technique: long-term results.
AB  - Endovascular intervention deploying a kissing stents (KS) technique has been used
      as an alternative to surgical intervention in treating symptomatic aortoiliac
      occlusive disease. However, the long-term results on high-risk patients are
      unknown. We retrospectively analyzed data on high-risk patients who underwent
      endovascular intervention using the KS technique at our institution. Fifty high
      risk patients aged 62 +/- 6.4 years with severe aortoiliac stenosis underwent
      stent-supported angioplasty using the KS technique. Thirty percent of the
      patients had total occlusion of the distal aorta and/or the iliac arteries.
      Twelve patients received thrombolytics prior to stenting. The procedure was
      successful in all 50 patients. There was a 4% acute complication rate (distal
      embolization). However, there were no vascular complications, myocardial
      infarction, or perioperative death. Primary patency during follow-up of 20 +/-
      12.3 months was 92%, while secondary patency rate was 100%. Amputation-free
      survival was 100%. Ninety-two percent remained free of lifestyle-limiting
      claudication.

PMID- 14571481
TI  - Aortoiliac stenting: "kiss of death?".

PMID- 14571482
TI  - Percutaneous intervention for the treatment of hypoplastic aortoiliac syndrome.
AB  - Hypoplastic aortoiliac syndrome (HAIS) occurs in young women and is characterized
      by a small infrarenal aorta with a hypoplastic iliofemoral arterial system and
      advanced atherosclerotic disease. Of 304 aortoiliac interventions (AoI), 30
      female patients (mean age, 50 +/- 5 years) had HAIS. HAIS patients were less
      likely to have coronary disease (33% vs. 88%; P < 0.0001) or diabetes (10% vs.
      42%; P < 0.001) compared to their AoI counterparts. Twenty-three patients (73%)
      had hyperlipidemia with mean cholesterol of 287 +/- 42 mg/dl. Twenty-eight
      patients (93%) were successfully treated with AoI. The ankle/brachial indices
      improved from pre-AoI ABI of 0.55 +/- 0.1 to post-AoI ABI of 0.99 +/- 0.1.
      Complications included one groin hematoma and one case of thrombosis. Follow-up
      averaged 31 months (range, 3-91 months) with an early (less than 12 months)
      restenosis rate of 7% and late (greater than 12 months) restenosis of 21%. One
      patient (3%) required surgical revascularization for persistent symptoms.
      Percutaneous treatment of HAIS is an alternative to surgical revascularization
      with satisfactory long-term results.

PMID- 14571483
TI  - Percutaneous intervention of spontaneous renal artery dissection complicated with
      renal infarction: a case report and literature review.
AB  - Spontaneous renal artery dissection (SRAD) is a rare condition that occurs before
      renal infarction. Using percutaneous intervention to treat SRAD remains
      controversial because it is not clear whether it is feasible or effective. We
      describe a 48-year-old male patient with SRAD complicated with renal infarction
      who was successfully treated with percutnaeous angioplasty and renal artery
      stenting.

PMID- 14571484
TI  - Clinical impact of abciximab on long-term outcome after complex coronary
      angioplasty.
AB  - Glycoprotein IIb/IIIa receptor antagonists, such as abciximab, are used to reduce
      major adverse cardiac events (MACEs) in patients undergoing percutaneous
      transluminal coronary angioplasty. The goal of this study was to evaluate the
      administration of abciximab in relation to lesion complexity and periprocedural
      complications. A total of 357 patients with 435 de novo lesions were included in
      this study. Lesions were divided into simple (type A and type B1) and complex
      (type B2 and type C) lesions according to the American College of
      Cardiology/American Heart Association Task Force lesion complexity system.
      Abciximab was given to unstable complex lesions and simple lesions with a
      periprocedural unstable complicated course. The overall incidence of MACE during
      the 9-month follow-up period was 17.0%. Patients treated with abciximab had a
      higher lesion complexity (P < 0.001), dissections (P = 0.014), stents (P <
      0.001), and vessels involved (P < 0.001). in addition, the abciximab group was
      characterized by a higher angina NYHA class (P = 0.005), lower TIMI flow prior to
      stenting (P = 0.01), and a longer total inflation time (P = 0.006). Despite these
      clinical differences, the occurrence of MACE within the abciximab group was
      slightly less than in the group without abciximab (16.2% and 17.3%,
      respectively). Lesion complexity was directly related to MACE in the group that
      did not receive abciximab (simple and stable complex lesions; P = 0.04). On the
      other hand, in subjects treated with abciximab, lesion complexity was not related
      to a higher incidence of MACE (P = 0.76). The use of abciximab equalizes the
      difference in outcome between simple and complex lesions. Therefore, abciximab
      should be advocated especially in unstable and complex percutaneous coronary
      interventions.

PMID- 14571486
TI  - How did we get here from there?

PMID- 14571485
TI  - Incidence and predictors of late total occlusion following coronary stenting.
AB  - To determine the incidence and predictors of total occlusion in-stent restenosis,
      we reviewed three randomized stent vs. stent trials and one stent registry, which
      provided 955 coronary artery lesions with 6-month angiographic follow-up. Fifteen
      (1.6%) of the 955 stented lesions were totally occluded at 6-month follow-up.
      Most patients with total occlusion presented with recurrent angina at the time of
      repeat angiography (60.0%) while no patient presented with an acute ST segment
      elevation myocardial infarction. The univariate predictors of total occlusion
      following elective coronary stenting included stenting for restenosis after a
      previous percutaneous intervention (P = 0.001), longer stent length (P < 0.001),
      longer lesion length (P < 0.001), smaller reference vessel diameter (P = 0.022),
      smaller preprocedure minimum lumen diameter (MLD; P = 0.004), and smaller
      postprocedure MLD (P = 0.036). Stepwise multiple logistic regression analysis
      demonstrated that stenting for restenotic lesions (P = 0.004), longer stent
      length (P < 0.001), and smaller preprocedure MLD (P = 0.012) were independent
      predictors of total occlusion following coronary stenting.

PMID- 14571487
TI  - Direct stent implantation without predilatation through 5 French guiding catheter
      following transfemoral coronary angiogram: a feasibility study.
AB  - Direct stenting (DS) is accepted as reducing procedural cost and duration and 5
      Fr guiding catheters as lowering peripheral vascular complications. We aimed to
      evaluate the feasibility and safety of both strategies. We retrospectively
      studied 150 consecutive patients treated with DS strategy using a 5 Fr femoral
      approach. A need for 6 Fr devices or balloon predilatation defined 5 Fr DS
      failure. Procedural success was defined as good angiographic result (residual
      stenosis < 30% and TIMI flow 3) without ischemic complications. A total of 161
      out of 174 lesions were elected as suitable for DS. The success rate of 5 Fr DS
      was 87.6% (141/161 lesions). The procedural success rate was 92% (138/150
      patients). The angiographic success rate was 96.3% (155/161 lesions). Other
      complications were six non-Q-wave MI and one repeat angioplasty for acute in
      stent thrombosis. Only one major peripheral vascular complication occurred.
      Direct stenting through 5 Fr guiding catheters in selected lesions is safe and
      effective with a low incidence of peripheral arterial complications.

PMID- 14571489
TI  - Effect of recanalization of chronic total occlusions on global and regional left
      ventricular function in patients with or without previous myocardial infarction.
AB  - Previous studies have demonstrated improvement of regional wall motion and global
      left ventricular function after successful recanalization of chronic total
      occlusion in coronary artery. However, the difference of benefits of
      recanalization between infarct site and noninfarct site is unknown. This study
      assessed the changes in left ventricular ejection fraction, regional wall motion
      after successful angioplasty of chronic total occlusions with or without previous
      myocardial infarction. This study also evaluated the factors that influenced the
      outcome of left ventricular function. We retrospectively studied 75 patients with
      a successfully recanalized chronic total occlusion in native coronary artery.
      Left ventriculograms were obtained at baseline and after 6 months. Global and
      regional left ventricular function were determined. The patients were divided
      into two groups. Group 1 comprised patients without previous myocardial
      infarction in the territories of total occlusion vessel that was recanalized.
      Group 2 comprised patients with previous myocardial infarction in the territories
      of total occlusion vessel that was recanalized. Left ventricular ejection
      fraction increased from 53.2% +/- 16.3% at baseline to 57.3% +/- 20.1% at 6-month
      follow-up in the whole group (P = 0.001). In group 1 patients, the evolution of
      left ventricular (LV) ejection fraction increased from 59.5% +/- 13.7% to 67.3%
      +/- 14.6% (P < 0.001). In group 2 patients, the evolution of LV ejection fraction
      increased, but not significantly, from 48.9% +/- 16.2% to 50.5% +/- 16.9% (P =
      NS). The evolution of LV ejection fraction increased from 47.6% +/- 17.4% to
      50.8% +/- 17.5% (P < 0.05) in the subgroup of recanalization in infarct-related
      vessel that had rich collateral circulation and had long-term patency. The
      regional wall motion all significantly improved in group 1 patients (P < 0.05).
      The regional wall motion did not change in group 2 patients (P = NS). The
      influence of recanalization of chronic coronary occlusions on the improvement of
      left ventricular global function was different between myocardial infarction and
      nonmyocardial infarction patients. The left ventricular function did not improve
      in myocardial infarction patient. Regional wall motion improved in patients
      without previous myocardial infarction. For reliable improvement of left
      ventricular function after recanalization of chronic total occlusions, evidence
      (not only by symptom or treadmill test) of viable myocardium in recanalized
      vessel is important. It is also important to keep patency of infarct-related
      vessel that has good collateral circulation for improving the left ventricular
      function.

PMID- 14571488
TI  - Stenting and glycoprotein IIb/IIIa inhibition in patients with acute myocardial
      infarction undergoing percutaneous coronary intervention: findings from the
      global registry of acute coronary events (GRACE).
AB  - Stenting and GP IIb/IIIa inhibition are promising adjunctive therapies in PCI.
      The Global Registry of Acute Coronary Events (GRACE) is a registry of unselected
      patients with acute coronary syndromes, allowing for the study of treatments in a
      real-world environment. Data from GRACE patients with AMI who underwent PCI were
      analyzed. After adjusting for demographics, baseline characteristics, and
      previous medications, treatment with GP IIb/IIIa inhibitors and a stent and
      treatment with a stent alone were significant predictors of survival at 6 months.
      Stents were used in 90.9% of patients. GP IIb/IIIa inhibitors were used in 59.7%;
      in most cases they were started after the beginning of the procedure. The in
      hospital death rate (7.6%) was highest in patients undergoing urgent PCI.
      Mortality at 6 months following PCI was 14.4% among patients who received neither
      GP IIb/IIIa inhibitors nor a stent, compared to patients who received both GP
      IIb/IIIa inhibitors and a stent (7.3%), GP IIb/IIIa inhibitors alone (12.8%), or
      a stent alone (6.7%).

PMID- 14571491
TI  - New catheter design for cannulation of the anomalous right coronary artery
      arising from the left sinus of valsalva.
AB  - Cannulation of an anomalous right coronary artery during coronary angiography and
      percutaneous intervention poses significant technical difficulties using
      currently available catheter shapes. We describe a new catheter design and the
      cannulation technique for application of this catheter. The initial experience
      with this catheter in cases is reported.

PMID- 14571490
TI  - Silicon carbide-coated stents in patients with acute coronary syndrome.
AB  - Silicon carbide (aSIC-C) is a stent coating with antithrombogenic as well as anti
      inflammatory properties as compared with uncoated stainless steal based on in
      vitro and in vivo studies. This study investigated the potential of this coating
      in patients with unstable angina. At 38 study sites, 485 patients were randomized
      to an aSIC-C (n = 238) or a conventional stainless steal stent (n = 247). Patient
      were classified according to angina at rest within last 48 hr to Braunwald in
      class IIB (= 314) and IIIB (n = 171). The primary endpoint was a combination of
      death, myocardial infarction, or ischemia-driven target vessel revascularization
      at 6 months. Complications of procedures performed at 0.4 +/- 1.1 days after
      admission occurred at lower rates than previously reported in this high-risk
      population, but the primary endpoint was not different between the study groups.
      Only in Braunwald class IIIB patients did the primary endpoint occur less
      frequently in patients with an aSIC-C stent as compared to patients with a
      conventional stent (5.8% vs. 15.3%; P = 0.049). At 9-month follow-up, the level
      of difference was maintained, but statistical significance was lost. Quantitative
      angiography revealed no significant difference between the stents in the
      subgroups. This study suggests that aSIC-C stents exert clinically measurable
      effects in patients with unstable angina with recent symptoms at rest. This
      coating deserves further clinical investigation and may serve as platform for
      antiproliferative drugs.

PMID- 14571492
TI  - Stenting for spontaneous left internal mammary artery dissection: a case report.
AB  - We present a case of a spontaneously occurring mid LIMA dissection found on
      routine cardiac catheterization. We report our evaluation and intervention for
      this exceedingly rare phenomenon.

PMID- 14571493
TI  - Myocardial perfusion during transient slow-flow in the patient with old vein
      graft intervention: assessment by serial measurement of pressure-derived
      fractional flow reserve and thermodilution-derived coronary flow reserve.
AB  - A patient with distal slow-flow after stenting in the old vein graft intervention
      was reported. This case is a first in whom guidewire-based serial measurement of
      pressure-derived fractional flow reserve (FFR(myo)) and thermodilution-based
      coronary flow reserve (CFR(thermo)) clearly demonstrated the serial change of
      microvascular circulation. During slow-flow, CFR(thermo) remained in low value
      despite significant improvement of FFR(myo) from 0.61 to 0.90. After thrombus
      aspiration and nicorandil injection, coronary flow reestablished immediately.
      CFR(thermo) improved significantly from 1.3 during slow-flow to 3.6 after
      restoration of flow.

PMID- 14571495
TI  - Beauty's only skin deep: surface technologies emerge in stenting.

PMID- 14571494
TI  - Synergistic effects of a novel nanoporous stent coating and tacrolimus on intima
      proliferation in rabbits.
AB  - To overcome the problem of in-stent restenosis, the concept of local delivery of
      antiproliferative or immunosuppressive drugs has been introduced into
      interventional cardiology. Local drug delivery can be achieved by drug-eluting
      stents coated with polymer surfaces used for controlled drug release. However,
      several polymer coatings have shown an induction of inflammatory response and
      increased neointima formation. In the present study, the effect of a new
      inorganic ceramic nanoporous aluminum oxide (Al(2)O(3)) coating on neointima
      proliferation and its suitability as a carrier for the immunosuppressive drug
      tacrolimus have been investigated. 316 L stainless steel coronary stents were
      coated with a 500 nm thin nanoporous aluminum oxide layer. This ceramic nanolayer
      was used as a carrier for tacrolimus. Bare stents (n = 6), ceramic coated stents
      (n = 6), and ceramic coated stents loaded with 60 (n = 7) and 120 mug (n = 6)
      tacrolimus were implanted in the common carotid artery of New Zealand rabbits.
      The ceramic coating caused no significant reduction of neointimal thickness after
      28 days. Loading the ceramic stents with tacrolimus led to a significant
      reduction of neointima thickness by 52% for 60 mug (P = 0.047) and 56% for 120
      mug (P = 0.036) as compared to the bare stents. The ceramic coating alone as well
      as in combination with tacrolimus led to a reduced infiltration of lymphocytes
      and macrophages in the intima in response to stent implantation. Ceramic coating
      of coronary stents with a nanoporous layer of aluminum oxide in combination with
      tacrolimus resulted in a significant reduction in neointima formation and
      inflammatory response. The synergistic effects of the ceramic coating and
      tacrolimus suggest that this new approach may have a high potential to translate
      into clinical benefit.

PMID- 14571496
TI  - Percutaneous mitral valve repair: a feasibility study in an ovine model of acute
      ischemic mitral regurgitation.
AB  - Annuloplasty is the cornerstone of surgical mitral valve repair. A percutaneous
      transvenous catheter-based approach for mitral valve repair was tested by placing
      a novel annuloplasty device in the coronary sinus of sheep with acute ischemic
      mitral regurgitation. Mitral regurgitation was reduced from 3-4+ to 0-1+ in all
      animals (P < 0.03). The annuloplasty functioned by reducing septal-lateral mitral
      annular diameter (30 +/- 2.1 mm preinsertion vs. 24 +/- 1.7 mm postinsertion; P <
      0.03). These preliminary experiments demonstrate that percutaneous mitral
      annuloplasty is feasible. Further study is necessary to demonstrate long-term
      safety and efficacy of this novel approach.

PMID- 14571497
TI  - Transcatheter left atrial appendage occlusion with Amplatzer devices to obviate
      anticoagulation in patients with atrial fibrillation.
AB  - It is assumed that over 90% of clinically apparent embolisms in atrial
      fibrillation originate from the left atrial appendage. Recently, a percutaneous
      method (PLAATO technique) to occlude the left atrial appendage to the end of
      preventing thromboembolic complications of atrial fibrillation has been
      introduced into clinical practice. This technique is quite intricate and requires
      general anesthesia. The Amplatzer atrial septal occluder lends itself for a more
      simple approach to this intervention. The first 16 patients treated at four
      centers are described. Their age varied from 58 to 83 years. All suffered from
      atrial fibrillation but eight of them were in sinus rhythm at the time of
      implantation. All but two procedures were done under local anesthesia of the
      groin only. There was one technical failure (device embolization) requiring
      surgery. All other patients left the hospital a day after the procedure without
      complications. There were no problems or embolic events during an overall follow
      up of 5 patient-years and all left atrial appendages were completely occluded
      without evidence of thrombosis at the atrial side of the device at the latest
      follow-up echocardiography. With the Amplatzer technique, the left atrial
      appendage can be percutaneously occluded with a venous puncture under local
      anesthesia, without echocardiographic guidance, and at a reasonable risk. It
      remains to be evaluated in larger series or randomized trials how the simpler
      Amplatzer technique compares with the complex PLAATO technique, and whether left
      atrial appendage closure is competitive with oral anticoagulation with warfarin
      or the novel ximelagatran to prevent thromboembolism in atrial fibrillation.

PMID- 14571498
TI  - Using eptifibatide in patients undergoing coronary angioplasty with acute
      myocardial infarction.

PMID- 14571499
TI  - Please let every acronym be defined (PLEAD).

PMID- 14571501
TI  - Intracoronary fracture and embolization of a coronary angioplasty balloon
      catheter: retrieval by a simple technique.

PMID- 14571502
TI  - The complication.

PMID- 14571504
TI  - Novel diterpenoids and hydrocarbons in the Dufour gland of the ectoparasitoid
      Habrobracon hebetor (Say) (Hymenoptera: Braconidae).
AB  - Chemical constituents contained in the Dufour gland of the ectoparasitoid
      Habrobracon hebetor (Say) (Hymenoptera: Braconidae) were characterized. Three
      terpenes, beta-springene, a homo-beta-springene, and a homo-geranyllinalool
      constitute approximately 37% of the gland components, with the remaining 63% all
      being hydrocarbons. The hydrocarbons consist of a homologous series of n-alkanes
      (n-C21 to n-C31), a trace amount of 3-methyl C23, a homologous series of
      internally methyl-branched alkanes (11-methyl C23 to 13-methyl C35), one
      dimethylalkane (13,17-dimethyl C33), a homologous series of monoenes (C(25:1) to
      C(37:1)) with the double bonds located at Delta9, Delta13 and Delta15 for alkenes
      of carbon number 25 to 31 and at Delta13 and Delta15 for carbon numbers 33 to 37
      and three homologous dienes in very low amounts with carbon numbers of 31, 32,
      and 33. The terpenoid and hydrocarbon composition of the Dufour gland was similar
      in virgin and mated females. However, in contrast to the hydrocarbons, the amount
      of beta-springene and homo-geranyllinalool increased significantly with time
      after adult emergence from the cocoon. Although many hydrocarbons in the Dufour
      gland are the same as those on the cuticle of this species [Howard and Baker,
      Arch. Insect Biochem. Physiol. 53:1-18 (2003)], substantial differences also
      occur. Of particular note is the chain length of alkenes and location of the
      double bonds: cuticular alkenes have a chain length of C23 to C29 and double bond
      locations at Delta5, Delta7, and Delta9, whereas the Dufour gland alkenes
      contains a greater range of carbon numbers and have no Delta5 or Delta7 alkenes.
      The Dufour gland contains only one of the long-chain dimethylalkanes found on the
      cuticle. Also, no terpenoids are found on the cuticle, and the Dufour gland
      contains none of the secondary wax esters that are major components on the
      cuticle. GC-MS analysis of lipids carried in the hemolymph of H. hebetor
      indicated that all hydrocarbons found on both the cuticle and in the Dufour gland
      are present, as are some of the wax esters. However, none of the terpenoids were
      detected in the hemolymph. This suggests that the hydrocarbons are synthesized in
      other tissues or cells, probably by oenocytes, and differentially partitioned
      between the cuticle and the Dufour gland. The terpenoids are most likely
      synthesized within the Dufour gland. Analysis of surface lipids from eggs laid
      within 18 h indicated that no diterpenoids were present. Rather, the lipids
      present on the eggs were n-alkanes, monomethylalkanes, alkenes, and secondary
      alcohol wax esters. This composition did not reflect that of the Dufour gland,
      hence eggs are not being coated with Dufour gland components during oviposition.

PMID- 14571505
TI  - Cloning and expression of male-specific protein (MSP) from the hemolymph of
      greater wax moth, Galleria mellonella L.
AB  - Male-specific protein (MSP) is a soluble protein that accumulates in high amounts
      in the hemolymph and other organs of adult male wax moth. The MSP was purified
      from adult male wax moth by gel filtration and reversed phase column
      chromatography, and its amino acid sequence was determined. Because of blocked N
      terminus, several internal amino acid sequences of MSP were obtained by the in
      gel digestion method using trypsin. RT-PCR was conducted using degenerate primers
      designed from the internal amino acid sequences. 5'-RACE PCR was used to obtain
      the complete coding region and 5'-UTR sequence. The full length MSP cDNA sequence
      encodes a 239 amino acid polypeptide with an 18 amino acid signal peptide. The
      putative mature MSP has a molecular mass of 24,317 Da and an isoelectric point
      (pI) of 6.00, but shows a molecular mass of 27 kDa on SDS-PAGE. Sequence
      alignment showed a significant similarity between MSP and juvenile hormone
      binding proteins (JHBPs) of several lepidopteran species, including G.
      mellonella.

PMID- 14571506
TI  - Regulation of juvenile hormone biosynthesis in Heliothis virescens by Manduca
      sexta allatotropin.
AB  - In Heliothis virescens, reproduction is strictly dependent on juvenile hormone
      (JH). In females, mating induces a sharp increase in JH titers, which stimulates
      increased vitellogenin biosynthesis and higher rates of egg production. JH
      biosynthesis is presumably stimulated by production and/or release of stimulatory
      neuropeptides such as allatotropins. There is evidence that allatotropin of H.
      virescens may be structurally related to Manduca sexta allatotropin (Manse-AT).
      In a radiochemical in vitro assay, synthetic Manse-AT stimulated JH biosynthesis
      by corpora allata (CA) of virgin H. virescens females in a dose-dependent manner,
      but had no effect on CA activity in H. virescens males. In females, the CA showed
      a transient increase in sensitivity to Manse-AT shortly after mating. Several
      structurally related peptides stimulated CA activity to a similar extent as Manse
      AT. Corpora allata activity was stimulated by a Ca2+ ionophore, A23187. A
      membrane-permeable Ca2+ chelator, BAPTA/AM, antagonized the stimulatory effects
      of Manse-AT, suggesting that Manse-AT may enhance CA activity by increasing
      intracellular Ca2+ concentration.

PMID- 14571507
TI  - Xenorhabdus nematophilus inhibits p-bromophenacyl bromide (BPB)-sensitive PLA2 of
      Spodoptera exigua.
AB  - Xenorhabdus nematophilus is a Gram-negative symbiotic bacterium of the
      entomopathogenic nematode, Steinernema carpocapsae. The bacteria delivered into
      the insect hemocoel by the nematodes cause immunodepression of the target insects
      to protect host nematodes and themselves from the cellular immune reaction.
      Previous reports suggest that the immunodepression is caused by inhibition of the
      eicosanoid pathway that is known to be critically important to mediate cellular
      immunity. This study focused on the inhibitory effect of X. nematophilus on PLA2
      activity of Spodoptera exigua. The PLA2 activity was functionally associated with
      the activation cascade of prophenoloxidase (pPO). Dexamethasone (DEX), a specific
      PLA2 inhibitor, inhibited pPO activation completely at the higher doses of
      approximately 2.4 muM in vitro condition. The inhibitory effect of DEX was
      reversed by the addition of arachidonic acid, the catalytic product of PLA2. By
      means of this in vitro PLA2 inhibitor assay system, two different PLA2 inhibitors
      were used to compare their inhibitory effects on the hemolymph PLA2 of S. exigua.
      p-Bromophenacyl bromide (BPB), a specific inhibitor of secretory PLA2 (sPLA2),
      significantly inhibited pPO activation, but methylarachidonyl fluorophosphates
      (MAFP), a specific inhibitor of cytosolic PLA2 (cPLA2), did not show any
      inhibitory effect. BPB also inhibited pPO activation of the plasma, though much
      higher PO activation and its inhibition by BPB was found in the hemocytes. Growth
      medium of X. nematophilus at the stationary phase had a PLA2 inhibitory effect.
      Via the in vitro PLA2 inhibitor assay, it was shown that the ethyl ether extract
      of the medium contained significant PLA2 inhibitor activity. These results
      indicate that X. nematophilus produces and secretes PLA2 inhibitor, which acts on
      BPB-susceptible PLA2 of S. exigua.

PMID- 14571508
TI  - Reduction in injury rates in nursing personnel through introduction of mechanical
      lifts in the workplace.
AB  - BACKGROUND: Health care workers incur frequent injuries resulting from patient
      transfer and handling tasks. Few studies have evaluated the effectiveness of
      mechanical lifts in preventing injuries and time loss due to these injuries.
      METHODS: We examined injury and lost workday rates before and after the
      introduction of mechanical lifts in acute care hospitals and long-term care (LTC)
      facilities, and surveyed workers regarding lift use. RESULTS: The post
      intervention period showed decreased rates of musculoskeletal injuries (RR =
      0.82, 95% CI: 0.68-1.00), lost workday injuries (RR = 0.56, 95% CI: 0.41-0.78),
      and total lost days due to injury (RR = 0.42). Larger reductions were seen in LTC
      facilities than in hospitals. Self-reported frequency of lift use by registered
      nurses and by nursing aides were higher in the LTC facilities than in acute care
      hospitals. Observed reductions in injury and lost day injury rates were greater
      on nursing units that reported greater use of the lifts. CONCLUSIONS:
      Implementation of patient lifts can be effective in reducing occupational
      musculoskeletal injuries to nursing personnel in both LTC and acute care
      settings. Strategies to facilitate greater use of mechanical lifting devices
      should be explored, as further reductions in injuries may be possible with
      increased use.

PMID- 14571509
TI  - Association of expired nitric oxide with urinary metal concentrations in
      boilermakers exposed to residual oil fly ash.
AB  - BACKGROUND: Exposure to metal-containing particulate matter has been associated
      with adverse pulmonary responses. Metals in particulate matter are soluble, hence
      are readily recovered in urine of exposed individuals. This study investigated
      the association between urinary metal concentrations and the fractional
      concentration of expired nitric oxide (F(E)NO) in boilermakers (N = 32) exposed
      to residual oil fly ash (ROFA). METHODS: Subjects were monitored at a boiler
      overhaul site located in the New England area, USA. F(E)NO and urine samples were
      collected pre- and post-workshift for 5 consecutive workdays. Metals investigated
      included vanadium (V), chromium (Cr), manganese (Mn), nickel (Ni), copper (Cu),
      and lead (Pb). RESULTS: The median F(E)NO was 7.5 ppb (95% CI: 7.4-8.0), and the
      median creatinine-adjusted urinary metal concentrations (mug/g creatinine) were:
      vanadium, 1.37; chromium, 0.48; manganese, 0.30; nickel, 1.52; copper, 3.70; and
      lead, 2.32. Linear mixed-effects models indicated significant inverse exposure
      response relationships between log F(E)NO and the log-transformed urinary
      concentrations of vanadium, manganese, nickel, copper, and lead at several lag
      times, after adjusting for smoking status. CONCLUSIONS: Urine samples may be
      utilized as a biomarker of occupational metal exposure. The inverse association
      between F(E)NO and urinary metal concentrations suggests that exposure to metals
      in particulate matter may have an adverse effect on respiratory health.

PMID- 14571510
TI  - Utility of a routine medical surveillance program with benzene exposed workers.
AB  - BACKGROUND: A medical surveillance program of benzene-exposed workers has to be
      established in such a way as to observe early signs of benzene-induced cytopenia,
      pancytopenia, or leukemia. This study evaluates the utility of routine medical
      survey applied to benzene-exposed workers by analyzing the hematological,
      immunological, and cytogenetic assay results. METHODS: The results of a previous
      study of hematological, immunological, and cytogenetic assays in benzene-exposed
      workers (up to 15 ppm) are used to discuss medical surveillance program by
      defining the relationship between various benzene exposure concentrations and
      toxic endpoints. RESULTS: Exposure to benzene concentration lower than 5 ppm does
      not produce any abnormal hematological measurements. For benzene cumulative
      exposure above 100 (ppm-years), some blood indices [mean corpuscular volume
      (MCV), mean corpuscular hemoglobin concentration (MCHC), band neutrophils] show
      significant differences in comparison to the control group. The incidence of
      dicentric chromosomes was higher and the level of B-lymphocytes was lower even
      with workers exposed to 5 ppm of benzene; correlation with exposure indicators
      was not found. CONCLUSIONS: The results suggest that peripheral blood indices,
      although not sensitive enough, are still the most suitable parameters in a health
      surveillance program applied to benzene-exposed workers. B-lymphocytes could be a
      promising indicator of the benzene-induced damage. Cytogenetic tests did not
      prove to be suitable. Further investigation of useful screening tests for health
      surveillance program of benzene-exposed workers is still required.

PMID- 14571511
TI  - Biological indices of kidney involvement in personnel exposed to sevoflurane in
      surgical areas.
AB  - BACKGROUND: Fluoride, a main metabolite, and one degradation product of
      sevoflurane (SEV), called Compound A, are known to cause kidney effects in
      experimental animals. Other than in volunteers and patients, no research is
      available on exposed workers. The possible effects on the kidney in workers
      exposed in surgical areas were studied. METHODS: Subjects exposed to SEV and
      nitrous oxide (N(2)O) in surgical areas (N = 61) using open (N = 25) or semi
      closed (N = 36) circuits were submitted to biological monitoring. The same
      biological indices were determined in 43 controls also. Sevoflurane (SEVU),
      nitrous oxide (N(2)OU), total urinary proteins (TUP), N-acetyl-beta-D
      glucosaminidase (NAGU), and glutamine synthetase (GSU) were measured in urine.
      RESULTS: The mean values of environmental exposure were 31.3 ppm (range 0.9-111.6
      ppm) for N(2)O and 0.28 ppm (range 0-1.88 ppm) for SEV. Exposed subjects had
      significantly higher excretion of TUP; a higher, not significant, excretion of
      GSU was also observed in subjects using open circuits. A significant correlation
      was found in all exposed subjects between NAGU and SEVU (r = 0.303, P < 0.05),
      GSU and N(2)OU (r = 0.382, P < 0.01) and, especially, GSU and SEVU (r = 0.650, P
      < 0.001). These correlations appeared to be influenced by the use of open
      circuits; infact, NAGU was well correlated to N(2)OU (r = 0.770, P < 0.001) and
      SEVU (r = 0.863, P < 0.001); GSU to N(2)OU (r = 0.468, P < 0.05) and SEVU (r =
      0.735, P < 0.001). CONCLUSIONS: Results show that no relevant effect on the
      kidney is present for the levels of exposure studied. Nevertheless, correlation
      between dose and response urinary indices supports that SEV, other than N(2)O,
      may influence kidney function, especially when open circuits are used.

PMID- 14571512
TI  - Downsizing and health at the United States Department of Energy.
AB  - BACKGROUND: Downsizing and reorganization not only affect workers who lose their
      jobs, but even workers who retain their jobs are affected in negative ways. The
      present study measured how downsizing was accomplished at five Department of
      Energy facilities by evaluating communication with workers, perceived fairness of
      the process, and job characteristics, and how each of these were associated with
      worker health and well-being. METHODS: The researchers collected quantitative
      data using structured surveys, and captured qualitative data using interviews,
      focus groups, and open-ended survey responses. RESULTS: Employees, who felt that
      the downsizing process was fair, and that communication was open and honest,
      reported fewer medical symptoms, lower survivor syndrome, and more job security
      than their counterparts. Employees who were less immediately impacted by
      downsizing reported fewer medical symptoms than those who were more directly
      involved (e.g., delivered layoff notices, changed jobs, etc.) Thus, downsizing
      appears to affect the health of survivors, through the effects of the downsizing
      process. CONCLUSION: This examination of the effect of downsizing on the physical
      and mental health of surviving employees supports the conclusion that the impact
      of downsizing is not limited to those who lose their jobs and highlights the
      potential repercussions of downsizing on the emotional health of employees.

PMID- 14571513
TI  - Risk factors in health, work environment, smoking status, and organizational
      context for work disability.
AB  - BACKGROUND: This study examines the associations between health, work environment
      exposures, smoking status, and organizational context and work disability.
      METHODS: In a sample of 3,318 Danish employees, respondents were interviewed by
      telephone in 1995 about health, work environment, smoking status and
      organizational context of the workplace. In 1997, a follow-up to assess
      employment status was conducted using The Statistical Register of Transfer
      Payments, Statistics Denmark. RESULTS: Work disability is predicted by work
      environment, smoking status of the individual employee, and by organizational
      level factors at the workplace. Although poor mental health, chronic bronchitis
      or musculoskeletal symptoms in neck or shoulders were equally distributed at
      baseline among type of company, the 2-year incidence of work disability was
      higher in traditionally organized workplaces than in flexibly organized
      workplaces. CONCLUSION: The study suggests a potential for reducing health
      related work disability from work through flexible organization of the workplace.

PMID- 14571514
TI  - Non-fatal injuries in the West Virginia logging industry: using workers'
      compensation claims to assess risk from 1995 through 2001.
AB  - BACKGROUND: The logging industry has a high rate of both fatal and non-fatal
      injuries in comparison to other industries, and plays a vital role in WV's
      economy. METHODS: Workers' compensation (WC) injury claims and employment data
      were summarized to examine patterns and rates of non-fatal logging injuries in WV
      from 1995 through 2001. RESULTS: The average annual rate of injury claims was
      16.0 per 100 workers per year with rates remaining relatively steady over the 7
      year study period. The highest rates of injury were a result of being struck by
      an object, typically trees, snags, or logs. CONCLUSIONS: WV loggers most often
      file injury claims as a result of being struck by trees and tree parts, snags,
      and logs. Assessment of risk is a critical component in helping regulators,
      researchers, and the logging industry develop viable prevention strategies to
      reduce the incidence and severity of logging-related injuries.

PMID- 14571515
TI  - Fatal injuries to teenage construction workers in the US.
AB  - BACKGROUND: The construction industry is second only to agriculture in the annual
      number of fatal injuries in workers less than 18 years of age. We examined fatal
      injury reports for youth and adult workers to determine risk factors for injury
      and applicability of existing child labor regulations. METHODS: The US
      Occupational Safety & Health Administration (OSHA) investigation data for fatal
      work injuries from 1984 through 1998 were reviewed with respect to type of event,
      employer characteristics, and apparent violations of existing child labor laws
      under the Fair Labor Standards Act (FLSA). We also examined whether the employer
      met exemption criteria for federal enforcement of child labor or OSHA
      regulations. RESULTS: The fatality rate for teenage construction workers age 19
      and younger was 12.1 per 100,000 per year, slightly less than for adult workers.
      Teenage workers who were fatally injured were more likely than adults to have
      been employed at non-union construction firms (odds ratio (OR) = 4.96, P < 0.05),
      firms with fewer than 11 employees (OR = 1.72, P < 0.05), and their employers
      were more likely to have been cited by OSHA for safety violations (OR = 1.66, P <
      0.05) than for firms which were investigated because of a fatality in an adult
      worker. Fatalities in teenagers were more likely to occur in special construction
      trades such as roofing. Among fatalities in workers less than 18 years of age,
      approximately one-half (49%) of the 76 fatal injuries were in apparent violation
      of existing child labor regulations. We estimated that in 41 of the 76 cases
      (54%) the employer's gross annual income exceeded the $500,000 threshold for
      federal enforcement of child labor laws. Only 28 of 76 cases (37%) were at
      construction firms with 11 or more employees, which are subject to routine OSHA
      inspections. CONCLUSIONS: Fatal injuries in teenage construction workers differed
      from those in adults in that they were more likely to be at small, non-union
      firms of which a substantial proportion were exempt from federal enforcement of
      child labor laws and from routine OSHA inspections. Safety programs for young
      construction workers should include small, non-union construction firms and those
      in special construction trades such as roofing. We did not identify specific
      areas for new regulation but the number of fatalities reviewed was small.

PMID- 14571516
TI  - Information dissemination and use: critical components in occupational safety and
      health.
AB  - BACKGROUND: Information dissemination is a mandated, but understudied,
      requirement of occupational and environmental health laws and voluntary
      initiatives. Research is needed on the factors that enhance and limit the
      development, transfer, and use of occupational safety and health information
      (OSH). Contemporary changes in the workforce, workplaces, and the nature of work
      will require new emphasis on the dissemination of information to foster
      prevention. METHODS: Legislative and regulatory requirements and voluntary
      initiatives for dissemination of OSH information were identified and assessed.
      Literature on information dissemination was reviewed to identify important issues
      and useful approaches. RESULTS: More than 20 sections of laws and regulations
      were identified that mandated dissemination of occupational and environmental
      safety and health information. A four-stage approach for tracking dissemination
      and considering the flow of information was delineated. Special areas of
      dissemination were identified: the information needs of the changing workforce,
      new and young workers; small businesses; and workers with difficulty in
      understanding or reading English. CONCLUSIONS: We offer a framework for
      dissemination of OSH information and underscore the need to focus on the extent
      to which decision-makers and others receive and use such information. More solid
      data are also needed on current investments in disseminating, diffusing and
      applying OSH information and on the utility of that information. Am. J. Ind. Med.
      44:515-531, 2003. Published 2003 Wiley-Liss, Inc.

PMID- 14571517
TI  - Power calculations for survival analyses via Monte Carlo estimation.
AB  - BACKGROUND: Power calculations can be a useful step in the design of
      epidemiologic studies. For occupational and environmental cohort studies,
      however, the calculation of statistical power has been difficult because
      researchers are often interested in situations where exposure assignment is time
      dependent, and in research questions that pertain to cumulative exposure
      mortality trends evaluated with statistical methods for survival analysis. These
      conditions are not easily accommodated by available software or published
      formulas for power calculation. METHODS: Monte Carlo methods can be used to
      estimate statistical power for survival analyses. Simple computer programs are
      presented to illustrate this approach. RESULTS: We show that, for the simple case
      of a randomized clinical trial involving a dichotomous exposure, the results of
      power calculations derived via this Monte Carlo approach conform to values
      derived using a previously published formula. We then illustrate how the Monte
      Carlo approach may be extended to obtain estimates of statistical power for
      analyses of cumulative exposure-mortality trends under conditions more typical of
      occupational cohort studies. CONCLUSIONS: The Monte Carlo approach provides a way
      to perform power calculations for a wide range of study conditions. The approach
      illustrated in this study should simplify the task of calculating power for
      survival analyses, particularly in epidemiologic research on occupational
      cohorts.

PMID- 14571518
TI  - Exposing the "myth" of ABC, "anything but chrysotile": a critique of the Canadian
      asbestos mining industry and McGill University chrysotile studies.
AB  - BACKGROUND: Beginning in the 1930s, the Canadian asbestos industry created and
      advanced the idea that chrysotile asbestos is safer than asbestos of other fiber
      types. METHODS: We critically evaluate published and unpublished studies funded
      by the Quebec Asbestos Mining Association (QAMA) and performed by researchers at
      McGill University. RESULTS: QAMA-funded researchers put forth several myths
      purporting that Quebec-mined chrysotile was harmless, and contended that the
      contamination of chrysotile with oils, tremolite, or crocidolite was the source
      of occupational health risk. In addition, QAMA-funded researchers manipulated
      data and used unsound sampling and analysis techniques to back up their
      contention that chrysotile was "essentially innocuous." CONCLUSIONS: These
      studies were used to promote the marketing and sales of asbestos, and have had a
      substantial effect on policy and occupational health litigation. Asbestos
      manufacturing companies and the Canadian government continue to use them to
      promote the use of asbestos in Europe and in developing countries. Am. J. Ind.
      Med. 44:540-557, 2003.

PMID- 14571519
TI  - RE: Scrutinizing ACGIH risk assessments: the trichloroethylene case-Ruden C.,
      2003. Am J Ind Med 44:207-213.

PMID- 14571520
TI  - It's an inside job. Tenet moves Fetter to CEO: now he has to convince critics it
      doesn't take an outsider to solve the company's problems.
AB  - Tenet Healthcare Corp. has made it official-naming Trevor Fetter, left, the
      company's chief executive officer. He had served as acting CEO since Jeffrey
      Barbakow resigned last spring. Fetter had a lot going for him in the race for the
      post--he worked at Tenet and its spinoff Broadlane since 1995, but he faces many
      challenges at the troubled company.

PMID- 14571521
TI  - More, not better care. NCQA faults payment system for 'quality gaps'.

PMID- 14571522
TI  - Detailing performance. Report on K. C. area examines care differences.

PMID- 14571523
TI  - Eye of the storm. Medicare tempest hits over hospitals' priorities.

PMID- 14571524
TI  - Out of there. Up to eight partners terminated at Cap Gemini Ernst & Young,
      sources say.

PMID- 14571525
TI  - Secondary payer predicament. U.S. Justice Department probes insurers that billed
      Medicare as primary payer.

PMID- 14571526
TI  - Next stop: court. Challenges to California bills loom.

PMID- 14571527
TI  - A real alternative to cost-cutting. Managing the revenue cycle is an often
      ignored way to stay in the black.

PMID- 14571528
TI  - Balance past due. Hospitals use technology to get a handle on the thorny and
      complex issue of bad-debt collection.

PMID- 14571529
TI  - Employing IT for help wanted. Intermountain uses Internet to streamline the job
      application process--saving money, eliminating piles of paper and reducing
      turnover.

PMID- 14571530
TI  - Crossover sexual offenses.
AB  - Crossover sexual offenses are defined as those in which victims are from multiple
      age, gender, and relationship categories. This study investigates admissions of
      crossover sexual offending from sex offenders participating in treatment who
      received polygraph testing. For 223 incarcerated and 266 paroled sexual
      offenders, sexual offenses were recorded from criminal history records and
      admissions during treatment coupled with polygraph testing. The majority of
      incarcerated offenders admitted to sexually assaulting both children and adults
      from multiple relationship types. In addition, there was a substantial increase
      in offenders admitting to sexually assaulting victims from both genders. In a
      group of incarcerated offenders who sexually assaulted children, the majority of
      offenders admitted to sexually assaulting both relatives and nonrelatives, and
      there was a substantial increase in the offenders admitting to assaulting both
      male and female children. Although similar trends were observed for the sample of
      parolees, the rates were far less dramatic. Parolees appeared to have greater
      levels of denial, had participated in fewer treatment sessions, and perceived
      greater supervision restrictions as a result of admitting additional offenses.
      These findings support previous research indicating that many sexual offenders do
      not exclusively offend against a preferred victim type.

PMID- 14571531
TI  - An evaluation of the Bumby RAPE and MOLEST scales as measures of cognitive
      distortions with civilly committed sexual offenders.
AB  - Cognitive distortions are commonly viewed as an important factor in the
      assessment and treatment of sexual offenders. However, consensus about the
      operational definition of cognitive distortions and the best instrument to
      measure such distortions is lacking. This paper evaluates the Bumby MOLEST and
      RAPE scales as measures of cognitive distortions with patients civilly committed
      under California's Sexually Violent Predator law. Rapists and child molesters in
      the current sample endorsed markedly fewer cognitive distortions than the sexual
      offenders in Bumby's original study (K. M. Bumby, 1996). It is suggested that
      current self-report measures such as the MOLEST and RAPE scales are too
      susceptible to a socially desirable response set to provide useful data with
      sexual offenders who are involuntarily committed for treatment.

PMID- 14571532
TI  - Principles and techniques for maximizing the effectiveness of group therapy with
      sex offenders.
AB  - Group-based interventions are widely used as the preferred method for the
      treatment of sexual offenders. However, little attention has been given to the
      vital interpersonal processes within groups, which contribute to their
      therapeutic effect. This paper describes specific principles and techniques of
      group therapy that will help sex offender treatment practitioners take full
      advantage of this unique modality and thereby maximize the positive impact of
      treatment. In contrast to an individual-focused style that characterizes many sex
      offender treatment groups, group-focused interventions involve all group members
      and use the social/relational energy that is essential to the group modality.

PMID- 14571533
TI  - Measuring motivation to change in sexual offenders from institutional intake to
      community treatment.
AB  - Changes in motivational levels occurring during various stages of treatment
      (institutional and community) were measured among 101 federally sentenced sexual
      offenders in the Ontario region. Motivation was conceptualized as a dynamic
      process that can be construed from behavioral referents and more global
      evaluations of internal features/readiness/psychological stance. Five
      motivational indices were examined: acceptance of guilt for the offense;
      acceptance of personal responsibility for the offense; disclosure of personal
      information; motivation to change behavior; and participation in treatment.
      Offender scores on these indices were evaluated using the Goal Attainment Scaling
      protocol (T. Hogue, 1994), at four stages of the treatment process: (1) at
      institutional assessment, (2) following institutional treatment, (3) upon
      conditional release to the community, and (4) following a 12-week period of
      community treatment. Results showed that motivation to change sexually deviant
      behavior was higher at the end of institutional treatment relative to the initial
      assessment. However, levels of motivation decreased upon conditional release to
      the community, with few offenders making significant rebounds following 12 weeks
      of community treatment. Admission of guilt and acceptance of personal
      responsibility (measured at community treatment) were both significantly
      associated with treatment outcome.

PMID- 14571534
TI  - Emotional loneliness in sexual murderers: a qualitative analysis.
AB  - This study compared levels of emotional loneliness between sexual murderers and
      rapists who had not gone on to kill their victim/s. All participants were life
      sentenced prisoners in the United Kingdom. Assessment consisted of a
      semistructured interview and was subjected to grounded theory analysis. This
      approach is defined as the breaking down, naming, comparing, and categorizing of
      data. As such, it is distinguished from other qualitative methods by the process
      of constant comparison. This continual sifting and comparing elements assists in
      promoting conceptual and theoretical development. The results of this process
      found that sexual murderers, compared to rapists, reported significantly higher
      levels of grievance towards females in childhood, significantly higher levels of
      peer group loneliness in adolescence, and significantly higher levels of self as
      victim in adulthood.

PMID- 14571535
TI  - Considerations on fantasy use by child molesters and exhibitionists.
AB  - In many sex offender treatment programs, the examination and replacement of
      deviant fantasy use with appropriate fantasy use is a well-established practice.
      This practice is based on the assumption that sexual offenders use deviant
      masturbatory fantasies prior and after committing sexual offenses, but the data
      available to support this assumption is fairly limited. This study attempted to
      test the validity of this assumption by finding out whether a majority of
      exhibitionistic offenders and child molesters used deviant masturbatory fantasies
      prior and/or after their first offense. Data analysis from 57 child molesters and
      25 exhibitionistic offenders indicate that a majority of these offenders used
      masturbatory deviant fantasies before and after their first offenses, but they
      tended to use significantly more deviant fantasies after they engage in their
      first actual offense. Content of deviant fantasies was examined in relation to
      victim specificity. There were no significant differences between the number of
      deviant fantasies reported about a specific victim versus the number of fantasies
      reported about a nonspecific victim. We found a significant positive correlation
      between the number of deviant fantasies reported and the number of months spent
      in treatment by child molesters, but not by exhibitionistic offenders. Some
      tentative explanations for these findings are offered, but further elucidation is
      necessary.

PMID- 14571536
TI  - Hypersexual desire in males: are males with paraphilias different from males with
      paraphilia-related disorders?
AB  - The assessment of current sexual behavior (fantasies, urges, and activities) and
      sexual preoccupation (measured in min/day) associated with both conventional
      (i.e., adult relationship-associated) or unconventional (paraphilia and
      paraphilia-related) sexual behavior were ascertained from a sample of 120
      consecutively evaluated males with paraphilias (PA; n = 88, including sex
      offender paraphiliacs; n = 60) and paraphilia-related disorders (PRD; n = 32). In
      addition, an assessment of hypersexual desire, defined as the highest sustained
      period (at least 6 months minimum duration) of persistently enacted sexual
      behavior (total sexual outlet/week [TSO] after age 15) was assessed. In almost
      all measures, the PA and PRD groups were not statistically significantly
      different. The average PA or PRD reported a mean hypersexual TSO of 11.7 +/- 7.3,
      a mean age of 21.6 +/- 7.1 years at onset of peak hypersexual behavior, and a
      mean duration of 6.2 +/- 7.6 years of hypersexual TSO. When the sample was
      stratified into three subgroups on the basis of the lifetime number of PAs + PRDs
      as a proxy measure of the severity of sexual impulsivity, the "high" group, with
      at least 5 lifetime PAs and PRDs, consisted of all paraphilic males,
      predominantly sex offenders, who self-reported the highest hypersexual desire
      (14.3 +/- 7.9), the highest current TSO/week (9.9 +/- 8.1), the most current
      sexual preoccupation (2-4 hr/day), and the highest likelihood of incarceration
      secondary to paraphilic sex-offending behavior. Although hypersexual desire, a
      quantitative measure of enacted sexual behaviours, may be a meaningful construct
      for clinically derived samples, the incidence and prevalence of hypersexual
      desire in community samples of males with paraphilias and paraphilia-related
      disorders is unknown.

PMID- 14571537
TI  - Who cares? The views of sexual offenders about the group treatment they receive.
AB  - This paper describes one of the first systematic focused attempts to elicit the
      views of sexual offenders about the treatment that they have received. The
      paucity of previous research in this area is suggested to be the result of
      negative societal attitudes towards sexual offenders, as exemplified by recent
      tabloid newspaper coverage of this population. It is suggested that these
      attitudes may have a negative impact upon the attitudes of clinicians and
      researchers, and thus upon the treatment offered to this client group. Therefore,
      it is argued that seeking the views of the clients is essential in order to
      ensure that treatment is relevant and reflexive, and promotes relapse prevention.
      A questionnaire was distributed to participants who had completed treatment
      groups run by the Psychology Service at a Regional Secure Unit and at a Probation
      Service Sexual Offender Unit. The questionnaire aimed to elicit their views of
      the group experience, including issues to do with programme structure and
      content, group process, and therapeutic style of group facilitators. The results
      (including a pilot study) indicated that, on the whole, participants' experiences
      of the group were positive, for example aspects of the group process,
      understanding and preventing reoffending. Some suggestions for the modification
      and development of future sexual offender treatment are outlined, based on the
      feedback from subjects, for example, consideration of alternative treatment
      modalities, enhancing the content of group sessions, improving the organization
      of groups and modifying the training of groups leaders.

PMID- 14571538
TI  - A comparison of anxiety and depression in sex offenders with intellectual
      disability and a control group with intellectual disability.
AB  - The aims of this study were to employ modified versions of the 21-item Beck
      Anxiety and Depression Inventories with a group of 16 sex offenders with mild
      intellectual disability and borderline intelligence and 16 control participants
      with similar levels of intellectual disability. Test-retest correlations found
      high reliability for both assessments across all participants. There was a
      significant differences between the scores of the 2 groups with the sex offenders
      reporting significantly lower levels of anxiety and depression than the control
      participants. The results are discussed by presenting hypotheses on the emotional
      stability in each group.

PMID- 14571539
TI  - The importance of offense characteristics, victimization history, hostility, and
      social desirability in assessing empathy of male adolescent sex offenders.
AB  - Empathy has been a focus of work with sex offenders; however, there are a limited
      number of studies supporting this as a deficit. The study investigated the
      reliability and validity of 3 scales of the Interpersonal Reactivity Index (IRI)-
      Empathic Concern [EC], Perspective-Taking [PT], and Personal Distress [PD]-
      within a clinical sample. These scales were also used to examine the differences
      in empathy among groups of sex offenders. One hundred and twenty-three male
      adolescent sex offenders (ages 12-19) completed a battery of psychometric
      measures that included the IRI during a sex-offender-specific assessment.
      Moderate internal consistency and convergent validity was established for IRI
      scales. Age and social desirability were related to IRI scores. Victim empathy
      was not related to IRI scores. Justifications and acceptance of sexual and
      interpersonal violence were negatively correlated to EC and positively correlated
      to PD. Those who committed violent offenses reported more EC and PT; however, a
      generally hostile temperament was negatively related to these scales. Group
      differences were not found when contrasted with respect to a history of sexual or
      physical victimization or denial. Researchers using the IRI with male adolescent
      sex offenders should be cautious of the influence of age and socially desirable
      responding.

PMID- 14571540
TI  - Circumferential change scores in phallometric assessment: normative data.
AB  - Phallometric testing is a procedure that has enjoyed considerable popularity as
      an objective component in the assessment of sexual offenders. The value of this
      procedure may be most notably compromised in the realm of interpretation, and
      problems in interpretation are particularly acute for those participants where
      full arousal is not obtained during testing. The calculation of Percent Full
      Erection (PFE) scores has of necessity involved a speculative component in such
      cases. Eliminating this speculation through empirical investigation was the
      purpose of the current research. Circumferential change scores (from flaccidity
      to full erection) were obtained for 724 respondents at nine North American
      correctional facilities, allowing for the calculation of descriptive statistics
      and a determination of the distribution characteristics of these scores. The
      results provide an empirical basis for calculating PFE scores and interpreting
      phallometric data in those cases where full arousal is not obtained, and specific
      confidence levels associated with interpretation are offered. It is suggested
      that only through a more rigorous application of the principles of science will
      the procedure of phallometric assessment fulfill its true potential.

PMID- 14571541
TI  - The use of actuarials at civil commitment hearings to predict the likelihood of
      future sexual violence.
AB  - Some have argued that acturarial methods such as the RRASOR, the MNSOSTR, and the
      Static-99, can outperform clinical judgments when utilized at a civil commitment
      hearing to make a prediction. Although actuarial data can be used to identify a
      group of persons to be considered for possible civil commitment, at present it
      cannot be used to accurately predict the likelihood of future acts of sexual
      violence with respect to any specific individual within such a group. For that
      reason, it might be best to restrict the use of acturial data to the initial
      screening process, rather than introducing it at the commitment hearing itself.

PMID- 14571542
TI  - Actuarial risk assessment: commentary on Berlin et al.
AB  - F. S. Berlin, N. W. Galbreath, B. Geary, and G. McGlone (this issue) have raised
      some important questions regarding the use of acturial risk assessment
      instruments in sex offender civil commitment proceedings, also known as sexually
      violent predator or SVP proceedings. Their primary point is that interpreting the
      findings of existing actuarial risk assessment instruments is a tricky business
      because it is not certain whether the extent to which probability estimates
      derived from group data can be applied to individual cases. I agree completely
      with Berlin et al. on this point, but disagree with them concerning the extent to
      which probability estimates--and, therefore, actuarial instruments--are legally
      relevant in SVP proceedings. I outline some potential problems with respect to
      the legal admissibility of actuarial instruments, including their legal
      relevance.

PMID- 14571543
TI  - Men in his category have a 50% likelihood, but which half is he in? Comments on
      Berlin, Galbreath, Geary, and McGlone.

PMID- 14571544
TI  - The Abel test.

PMID- 14571545
TI  - HIPAA reins in shadow charts, independent databases.

PMID- 14571546
TI  - From standards to schools: how advocacy affects the way we work.

PMID- 14571547
TI  - A nontraditional day in the life. Clinical resource management: driven by data.

PMID- 14571548
TI  - A nontraditional day in the life. Long-term acute care: the effect of PPS.

PMID- 14571549
TI  - A nontraditional day in the life. Software development: from conception to
      implementation.

PMID- 14571550
TI  - The life cycle of a project. How to plan for performance improvements.

PMID- 14571551
TI  - Working smart. Risk assessment: doing more with less.

PMID- 14571552
TI  - Working smart. The new accreditation survey: one health system's transition.

PMID- 14571553
TI  - Practice brief. Security risk analysis and management: an overview.

PMID- 14571554
TI  - Working smart. Cut, copy, paste: EHR guidelines.

PMID- 14571555
TI  - CPT category III codes cover new, emerging technologies. New codes developed to
      address issues in light of HIPAA.

PMID- 14571556
TI  - Choosing modalities for carotid stenosis.

PMID- 14571557
TI  - Another challenge: HCV infection.

PMID- 14571558
TI  - Hepatitis C virus/HIV coinfection: a new challenge for nurses in AIDS care.
AB  - HIV-infected patients are living longer owing to effective treatment with highly
      active antiretroviral therapy (HAART). As a result, the extent and impact of
      hepatitis C virus (HCV) infection in this patient population are now becoming
      apparent. HIV infection accelerates the progression of HCV to cirrhosis, endstage
      liver disease, and death. The presence of each disease also influences treatment
      of the other, and appropriate management of side effects (e.g., anemia,
      neutropenia, depression) is crucial for treatment success. The HIV nurse is well
      positioned to treat, counsel, and support the HIV/HCV-coinfected patient by
      encouraging screening and providing education on the side effects of treatment,
      the means of managing side effects, and the resources available to assist in
      problems of substance abuse and depression.

PMID- 14571559
TI  - Natural history and epidemiology of hepatitis C.
AB  - The high incidence of hepatitis C virus (HCV) makes it one of the greatest health
      threats facing the world today. Hepatitis C is the most common blood-borne
      infectious disease in the United States, and evidence demonstrates that if the
      disease is not contained it will continue to spread and the death rate from
      hepatitis C will rise to a level far greater than that of AIDS. The
      epidemiological patterns of hepatitis C transmission will be reviewed.

PMID- 14571560
TI  - Pathophysiology of hepatitis C and HIV coinfection.
AB  - Hepatitis C infection is the most common cause of chronic hepatitis that can lead
      to cirrhosis and hepatocellular cancer. Hepatitis C virus infects approximately
      70 million people worldwide. Hepatitis C is usually transmitted by injection drug
      use and blood transfusion. Hepatitis C is prevalent in HIV-infected individuals.
      Coinfection complicates the treatment of these two distinct viral infections.
      Understanding the normal functions of the liver and the pathophysiological
      effects of coinfection enables health care professionals to provide the highest
      level of care for these individuals.

PMID- 14571561
TI  - Treatment of hepatitis C virus in the coinfected patient.
AB  - Since hepatitis C virus (HCV) was first identified in 1989, the impact of HCV
      infection on the HIV-infected population has been steadily increasing. It is now
      known that HCV affects the course and treatment of HIV disease in coinfected
      individuals (those infected with both HCV and HIV). Although there are
      significant data regarding the treatment of HCV in non-coinfected individuals,
      there are numerous questions that still remain regarding how to monitor and treat
      HCV infection in the coinfected population. This article reviews the available
      data regarding treatment of HCV in the coinfected population as well as how these
      individuals should be monitored, before and during HCV therapy, as well as how to
      address the numerous side effects associated with HCV treatment. To meet the
      demands of the coinfected population. HIV nurses must be willing to expand their
      knowledge to support, educate, assess, and advocate for coinfected individuals.

PMID- 14571562
TI  - Neuropsychiatric changes in HIV/hepatitis C coinfected patients undergoing
      interferon therapy.
AB  - A large percentage of HIV-infected patients are coinfected with hepatitis C virus
      (HCV). Current treatment available for HCV combines interferon and ribavirin
      therapy for 6 months or longer. Interferon is associated with numerous
      neuropsychiatric side effects including depression, cognitive impairment,
      anxiety, and irritability. The potential for developing depression is
      particularly concerning with coinfection because the incidence of depression is
      higher in the HIV-seropositive population than in the general population. This
      article discusses the mechanism and prevalence of interferon-induced depression
      and the debate regarding appropriateness of treatment in certain segments of the
      HIV population. The role of antidepressants as both treatment and a prophylaxis
      against interferon-related depression is reviewed. Nurses have a critical role in
      the care of HIV/HCV coinfected patients who are undergoing treatment with
      interferon and ribavirin. They both assess for treatment readiness prior to
      initiation and provide close monitoring for the development of neuropsychiatric
      disturbances while on therapy.

PMID- 14571563
TI  - Sexual transmission of hepatitis C and early intervention.
AB  - The major risk factors for the transmission of hepatitis C virus (HCV) have been
      sharing needles for intravenous drug use (IDU) and receiving blood and blood
      products; however, recent findings suggest that HCV is being increasingly
      sexually transmitted, particularly among HIV-positive men who engage in high
      risk, unprotected sexual behaviors with other men. Sixteen HIV-positive patients
      were diagnosed with sexually acquired HCV infection at a leading London HIV
      outpatient treatment center during 2002. All 16 patients were homosexual males
      with no history of IDU who had been involved in high-risk, unprotected sexual
      behaviors, which included active and passive anal intercourse, fisting, rimming,
      and oral sex. Six patients (37.5%) in the cohort spontaneously cleared HCV
      infection and consequently tested negative for HCV RNA. The remaining 10 patients
      were all started on HCV treatment, which consisted of pegylated interferon alpha
      2b in combination with ribavirin. Three patients (43%) have achieved a
      significant reduction in HCV RNA after 12 to 24 weeks of HCV treatment. The
      earlier HCV seroconversion is detected and treated, the better the chance of
      achieving viral eradication.

PMID- 14571564
TI  - A model for integrating hepatitis C services into an HIV/AIDS program.
AB  - Service provision to persons with or at risk for hepatitis C (HCV) has become an
      important goal for local health departments across the nation. The shared routes
      of HIV and HCV, the high coinfection rate of HIV/HCV, and the lack of federal or
      state funding to support HCV programs are reasons for integrating hepatitis C
      screening and treatment services into existing HIV/AIDS programs. Such an
      integration of health services conserves resources. This article reviews the
      development and progress of a county public health department program's
      integration of HIV/AIDS and HCV services and provides recommendations for other
      HIV/AIDS programs that might be considering integration of HIV/AIDS and HCV
      services.

PMID- 14571565
TI  - Hepatitis C and HIV in incarcerated populations: fights, bites, searches, and
      syringes!
AB  - Implications of hepatitis C (HCV) infection in corrections settings and learning
      needs of nurses whose primary expertise is care of HIV-infected individuals will
      be presented. This target group of nurses who provide care for HCV-infected
      patients includes nurses working in corrections settings, and community settings,
      whose clients have been or will be incarcerated, and advanced practice nurses
      working in a variety of settings. For nurses who work in the community setting,
      background information is presented on characteristics of the incarcerated and
      the environments of some different settings where incarceration occurs, such as
      county, state, juvenile, and federal institutions. Barriers to HCV prevention,
      testing, and treatment for incarcerated people are unique and different than for
      those living in the community. These distinctions are an important area of
      knowledge for nurses caring for patients who are HCV positive or at risk, whether
      they are practicing in a community or correctional setting.

PMID- 14571566
TI  - It was 20 years ago today ... some say it's complex and vulnerable to political
      whims, but Medicare's PPS has helped impose order on hospital finances.
AB  - In October 1983, Medicare launched a new payment system that would no longer
      write hospitals a blank check. It was called the prospective payment system and
      became known simply as the PPS. With its 20-year anniversary looming, the
      program's fundamental strengths and weaknesses have become apparent. Although
      some say it's vulnerable to politics, most agree it has imposed order on hospital
      finances.

PMID- 14571567
TI  - Army of one. Most prominent insurance trade groups to merge.

PMID- 14571568
TI  - Lobbying offensive. Congress asked to limit physician investments.

PMID- 14571569
TI  - Claiming victory. Officials deem claims-sharing program a success.

PMID- 14571570
TI  - Stopping the clock. The CMS eases HIPAA compliance deadline.

PMID- 14571571
TI  - Final push. Experts testify new medical coding system in crucial.

PMID- 14571572
TI  - Reviewing restrictions. GAO report calls for easing of critical-access rules in
      rural areas.

PMID- 14571573
TI  - Another try. West Suburban set to merge with Chicago system.

PMID- 14571574
TI  - Premier's portfolio. Investments more extensive than revealed earlier.

PMID- 14571575
TI  - Aboard the insurance titanic. If you think employer coverage is worsening, try
      the individual market.

PMID- 14571576
TI  - It's a whole new ER. Forget the crowded waiting room. In fact, forget the waiting
      room altogether.

PMID- 14571578
TI  - Repeat performance. Sixty-eight facilities have frequented the 100 Top Hospitals
      list four times or more since 1993. Data obsession is a common trait.

PMID- 14571577
TI  - 100 top hospitals. They 'just do it better'. Elite group of hospitals making
      Solucient's annual list--including 31 newcomers this year--outperform their peers
      across the board.

PMID- 14571579
TI  - 10 questions for Lance Armstrong.

PMID- 14571580
TI  - Why Bush gets a bad rap on dirty air. But he still needs to tackle the real
      problem: greenhouse gases.

PMID- 14571581
TI  - Not using Physcape? Then you're probably losing money.

PMID- 14571582
TI  - Playing the insurance card game. A case for uniform health insurance ID cards.

PMID- 14571583
TI  - Lead on. Administrator leadership is pivotal in group practice.

PMID- 14571584
TI  - Overcoding? Use bell curve as guide only.

PMID- 14571585
TI  - How Medicare physician fee schedule would affect practices.

PMID- 14571586
TI  - The next big thing. How do your patients view the services they receive?

PMID- 14571587
TI  - Time and money. A look at message automation via a computerized patient record.

PMID- 14571588
TI  - Making waves. Stages and process of organizational change.

PMID- 14571589
TI  - Where did the money go? Administrators, physicians should read their explanations
      of medical benefits.

PMID- 14571590
TI  - A healthy benefits experience for your group.

PMID- 14571591
TI  - Fixing past mistakes. Answers to questions about reviews, refunds, disclosures.
AB  - A medical group must address practical and legal issues when it discovers
      improper payments, billing mistakes or alleged misconduct. Its response has a
      significant impact on how the charges are resolved. A group and its providers can
      come under fraud and abuse investigations, whistle-blower allegations and
      Medicare payment reviews. Many questions arise in response to billing errors or
      allegations of misconduct.

PMID- 14571592
TI  - For love of the profession. Award winners take leadership to new heights.

PMID- 14571593
TI  - From the ground up. Guidelines for the development of a group practice.

PMID- 14571594
TI  - Addressing an illness of the mind. Case study: employee mental health leave.
AB  - Medical practice managers know how to deal with employees who get physical
      illnesses. But they rarely face issues of impaired mental health, which can also
      affect an individual's performance. This article describes the circumstances,
      options and steps taken when such a crisis affected a valuable employee in a
      private surgical practice.

PMID- 14571596
TI  - How to get your message across simply and forcefully. Why your fund-raising mail
      should be ugly.

PMID- 14571597
TI  - Stay focused and on course--no matter what!

PMID- 14571595
TI  - Pharmacologic management of heart failure and left ventricular systolic
      dysfunction: effect in female, black, and diabetic patients, and cost
      effectiveness.

PMID- 14571598
TI  - Nonprofits without audit committees risk financial disaster.

PMID- 14571600
TI  - Taking charge of your daily routine, your calendar, your life.

PMID- 14571599
TI  - Using the principles of brand management to advance the goals of health care
      organizations.

PMID- 14571601
TI  - When the boss wants high performance, build your fund raising on time-tested
      principles.

PMID- 14571602
TI  - Tribal culture.

PMID- 14571603
TI  - Nursing kids on prozac.

PMID- 14571604
TI  - A seismic shift in sex-case law.

PMID- 14571605
TI  - In Iraq, in uniform, and in turmoil.

PMID- 14571606
TI  - The habits of highly creative people.

PMID- 14571607
TI  - [Clinical study on treatment of severe acute pancreatitis by integrative Chinese
      and Western medicine combined with somatostatin].
AB  - OBJECTIVE: To study whether the therapeutic effect could be enhanced by combined
      use of somatostatin and conventional integrative Chinese and western medicine
      (TCM-WM) in treating severe acute pancreatitis (SAP). METHODS: Sixty patients of
      SAP were randomly divided equally into the somatostatin group (Group A) and the
      baseline treated group (Group B), they were all treated with non-surgical TCM-WM
      treatment, but to Group A, the intravenous injection of somatostatin 250
      micrograms/h for 72 hrs continuously was given additionally. Laboratory
      parameters, condition of disease and therapeutic effect indexes, including
      occurrence of organic dysfunction, local complication and mortality, between the
      two groups were compared. RESULTS: The recovery of serum levels of amylase,
      lipase, C reaction protein, lactate dehydrogenase, aspartate aminotransferase, as
      well as the scores of APACHE II in Group A were quicker than those in Group B (P
      < 0.05). The occurrence of organic dysfunction and local complication in Group A
      were lower to those in Group B, but without statistic significance. Comparison of
      the mortality in the two groups showed insignificant difference (P > 0.05).
      CONCLUSION: The early stage short course of combined TCM-WM and somatostatin
      treatment could improve the condition of SAP, but its effect on mortality should
      be further verified by enlarging the sample size.

PMID- 14571608
TI  - [Preventive and treatment effect of composite Rhodiolae on acute lung injury in
      patients with severe pulmonary hypertension during extracorporeal circulation].
AB  - OBJECTIVE: To investigate the possibility of early prevention and treatment of
      acute lung injury by using composite Rhodiolae (CR) in patients with severe
      pulmonary hypertension during extracorporeal circulation. METHODS: Seventy-six
      patients with severe pulmonary hypertension screened out by color 2D-Doppler
      ultrasonography were randomly divided into the treated group (n = 40) and the
      control group (n = 36). The general treatment for the two groups, including
      preoperational preparation, operational procedure and conventional drug therapy,
      was the same. To the treated group, CR was administered 4 g every day (half the
      dose in children) at 7-10 day before and 5-7 day after the operation. The life
      signs, pulmonary ventilation parameters, arterial blood gas analysis were
      monitored and blood levels of TXB2, 6-keto-PGF1 alpha in both groups were
      determined in the fixed time points. RESULTS: The various parameters in the
      treated group were all better than those in the control group (P < 0.05 or P <
      0.01), the occurrence rate of acute lung injury and its mortality in the treated
      group were 7.5% (3/40) and 0% (0/3) respectively, while in the control group were
      19.4% (7/36) and 43% (3/7) respectively. CONCLUSION: CR has good preventive and
      treatment effect in treating complicated acute lung injury during extracorporeal
      circulation (cardiopulmonary bypass) in patients with pulmonary hypertension.

PMID- 14571609
TI  - [Exploration on the effect and mechanism of shenfu injection on resuscitation
      from general anesthesia].
AB  - OBJECTIVE: To investigate the effect and the mechanism of Shenfu injection (SFI)
      on the resuscitation from general anesthesia. METHODS: Forty patients who
      received selective abdominal surgery with general anesthesia for 3-4 hrs and ASA
      grade I-II were divided into two groups, the trial group and the control group,
      20 patients in each group. After being sent into the postanesthesia care unit
      (PACU), the trial group was treated with intravenous dripping of SFI 1.0 ml/kg
      and the control group was treated with intravenous dripping of equal volume of
      normal saline. All patients were observed in double blindly manner, the self
      ventilation recovery time, extubation time, the time of leaving PACU and their
      Glasgow coma scale (GCS) were recorded and compared. 2 ml of peripheral venous
      blood were taken to determine the plasma beta-endorphin (beta-EP) content at the
      time points of before (T1), 5 min (T2), 15 min (T3) and 30 min (T4) after
      dripping. RESULTS: The self ventilation recovery time, extubation time and time
      of leaving PACU in the trial group were all shorter than those in the control
      group (P < 0.01), the GCS in the trial group was better than that in the control
      group (P < 0.01). The plasma content of beta-EP raised gradually along the
      recovering of patients consciousness, as compared with the content before
      dripping (T1), it showed insignificant difference at time point T2 but
      significant difference at T3 and T4 comparison at the corresponding time point
      showed that the content at T1 and T2 were similar in the two groups (P > 0.05),
      but at T3 and T4, the content was higher in the trial group than that in the
      control group respectively (P < 0.01). CONCLUSION: SFI could accelerate the
      resuscitation after general anesthesia, the mechanism may be related with its
      action in raising plasma beta-EP level.

PMID- 14571610
TI  - [Controlled clinical study on 49 patients of SARS treated by integrative Chinese
      and Western medicine].
AB  - OBJECTIVE: To evaluate the efficacy of Integrative Chinese and western medicine
      (ICWM) in treating SARS. METHODS: By controlled paralled design, 49 patients of
      SARS were studied, they were divided into the control group (n = 29) and the ICWM
      group (n = 20). The former was treated according to the "Recommended Program for
      Treatment of SARS" provided by Health Ministry, by administering of such drugs as
      Ribavirin, Levofloxacin, Thymopentin, Azithromycin, etc, the latter was treated
      with the ICWM protocol for SARS of "Special Technological Action to Prevent and
      Treat SARS" provided by Science and Technology Ministry. RESULTS: (1) The time
      for improving symptom in the ICWM group was 5.10 days and that in the control
      group was 7.62 days, the difference between them was significant (P < 0.05); (2)
      The days and amount for use hormone before subtract in the two group were
      similar, with insignificant difference (P > 0.05); (3) The days and amount for
      use hormone after subtract in the two groups were significantly different (P <
      0.05); (4) The time for improving peripheral WBC count and absolute value of
      lymphocyte, as well as for absorption time of shadow in chest film were not
      different significantly between the two groups (P > 0.05). CONCLUSION: In
      treating SARS, ICWM was superior to the treatment with western medicine alone in
      aspects of improving clinical symptom, promoting recovery of immune function and
      absorption of lung inflammation, decreasing the dosage of hormone used and
      shortening the therapeutic course.

PMID- 14571611
TI  - [Evaluation on effect of integrative medical treatment on quality of life of
      rehabilitation stage in 85 patients with SARS].
AB  - OBJECTIVE: To evaluate the effect of integrative medical treatment (IMT) with
      serial Chinese recipes on quality of life (QOF) of rehabilitation stage in SARS
      patients. METHODS: Eighty-five SARS patients of rehabilitation stage were
      enrolled in the clinical study. They were divided into the IMT group (62 patients
      received serial Chinese recipes and western medicine) and the control group (23
      patients received western medicine alone). The serial Chinese recipes were given
      according to patients' syndrome, one dose per day for oral intake for 3 weeks.
      QOF scoring in patients was observed. RESULTS: QOF scoring in the IMT group
      before treatment was not significantly different from that in the control group.
      After 3 weeks treatment, it improved to some extent in both groups, but the
      improvement in the IMT group was superior to that in the control group in respect
      of total score and score of psychologic emotional factors. CONCLUSION: Serial
      Chinese recipe could improve QOF of rehabilitation stage in SARS patients.

PMID- 14571612
TI  - [Study on prevention and treatment of radiotherapy caused post-visual pathway
      injury in nasopharyngeal carcinoma patients by traditional Chinese medicine].
AB  - OBJECTIVE: To study the effect of TCM in preventing and treating post-visual
      pathway injury caused by radiotherapy (RT) for nasopharyngeal carcinoma (NPC).
      METHODS: Thirty-five patients of NPC were randomly divided into the RT group (n =
      17) and the RT + TCM group (n = 18), they were all received RT, but the latter
      was treated additionally with Jingming recipe, a Chinese recipe. The latent
      period and amplitude of evoked potential (EP) were measured before and after
      ending of RT, using multi-focusing visual evoked potential inspector. RESULTS:
      The latent time of EP, both upper and lower visual field, was prolonged
      significantly after RT in the RT group (P < 0.05), but not in the RT + TCM group
      (P > 0.05); the amplitude of EP of upper visual field lowered significantly (P <
      0.05) in the RT group but insignificantly in the RT + TCM group (P > 0.05); as
      for the EP amplitude of lower visual field, it was unaltered in RT group after RT
      (P > 0.05), but increased in the RT + TCM group (P < 0.05). CONCLUSION: The
      Chinese medicine Jingming recipe was effective in preventing and treating RT
      induced post-visual pathway injury.

PMID- 14571613
TI  - [Effect of kangxin capsule on homocysteine and beta-amyloid protein in vascular
      dementia patients].
AB  - OBJECTIVE: To observe the effect of Kangxin capsule (KXC) on homocysteine (HCY)
      and beta-amyloid protein (beta-Ap) in patients with vascular dementia. METHODS:
      Sixty-three patients with vascular dementia were randomly divided into two
      groups, the 33 patients in the treated group and the 30 in the control group.
      Basal treatment were given to both groups, besides, KXC was given to the treated
      group and Hydergine was given to the control group. The levels of plasma HCY,
      beta-Ap as well as the changes of mini mental state examination (MMSE), activity
      of daily living (ADL) and TCM Syndrome scoring were observed before and after
      treatment. RESULTS: KXC could significantly decrease the levels of HCY and beta
      Ap (P < 0.01), rise the MMSE scores, reduce ADL scores and ameliorate TCM
      Syndrome. CONCLUSION: KXC can effectively regulate the levels of HCY, beta-Ap in
      vascular dementia patients.

PMID- 14571614
TI  - [Hypotensive action of luohuo capsule and its effect on plasma adrenal medullin
      and tissue factor pathway inhibitor].
AB  - OBJECTIVE: To study the therapeutic effect of Luohuo Capsule (LHC) clinically.
      METHODS: Clinical trial on 90 patients were carried out adopting randomized,
      stratified, single-blinded and positive drug controlled method, by divided
      patients into the treated group (n = 60) and the control group (n = 30). The
      treated group was treated with LHC, which was mainly consisted of Leech, Radish
      seed, Water-plantain Tuber, Chuanxiong, etc. The control group was treated with
      Beijing Hypotensive. No. 0. The therapeutic course was 4 weeks. The diagnosis and
      efficacy evaluation were in accord with corresponding national standards, using
      the indexes including safety, clinical symptoms, blood pressure, hemorrheologic
      parameters, blood lipid, adrenal medullin (AdM) and plasma tissue factor pathway
      inhibitor (TFPI). RESULTS: The total effective rate of LHC in lowering blood
      pressure in the treated group and the control group was 85.00% and 86.67%
      respectively, comparison of them showed no significant difference (P = 0.915).
      Most of the improvement of clinical symptoms in the treated group were better
      than those in the control group (P < 0.05 or P < 0.01). LHC could also improve
      the hemorrheologic status (P < 0.01), alleviate the blood lipids disorder (P <
      0.05), and adjust AdM and TFPI (P < 0.05). CONCLUSION: LHC is safe in treating
      hypertension grade I and II with no adverse reaction.

PMID- 14571615
TI  - [Clinical study on effect of zhifeng huatan pingxiao recipe in treating attack
      stage of child asthma].
AB  - OBJECTIVE: To observe the therapeutic effect of Zhifeng Huatan Pingxiao recipe
      (ZHPR) in treating attack stage of child asthma. METHODS: Sixty child asthma
      patients with attack of mild and moderate degree were randomly divided into the
      treated group (40 patients treated with ZHPR) and the control group (20 patients
      treated with western medicine). The therapeutic effect and laboratory indexes,
      including peripheral eosinophil count (EOS), serum immunoglobulin E (IgE) and
      plasma endothelin (ET), before and after treatment were observed. RESULTS: The
      total effective rate in the treated group was 72.5%, which was not different to
      that in the control group (P > 0.05). The therapeutic effect between different
      TCM types (heat and cold types) in the treated group was not different
      significantly (P > 0.05). ET, IgE and EOS levels all lowered after treatment in
      the treated group, but as compared with those in the control group, the
      difference was insignificant (P > 0.05). CONCLUSION: The therapeutic effect of
      ZHPR in treating child asthma attack stage is equivalent to that of western
      medicine, it shows actions in improving laboratory indexes.

PMID- 14571616
TI  - [Effect of dihydro-qinghaosu on auto-antibody production, TNF alpha secretion and
      pathologic change of lupus nephritis in BXSB mice].
AB  - OBJECTIVE: To investigate the effect of dihydro-qinghaosu (DQHS) on auto-antibody
      production, TNF alpha secretion and pathologic change of lupus nephritis in BXSB
      mice and the possible mechanism of DQHS in treating systemic lupus erythematosus
      (SLE). METHODS: Anti ds-DNA antibody and TNF alpha in serum of the BXSB mice were
      detected by enzyme linked immunosorbent assay (ELISA). Renal tissue was stained
      by HE and Masson. RESULTS: In the height and moderate dose DQHS groups, as
      compared with the model group, levels of anti-ds-DNA antibody and serum TNF alpha
      were significantly lower (P < 0.05); and renal pathological change was milder.
      CONCLUSION: DQHS could inhibit the production of anti-ds-DNA antibody and
      secretion of TNF alpha and improve the pathologic lesion of lupus nephritis in
      BXSB mice.

PMID- 14571617
TI  - [Effect of Panax notoginsenosides on the proliferation of hematopoietic
      progenitor cells in mice with immune-mediated aplastic anemia].
AB  - OBJECTIVE: To study the effect of panax notoginsenosides (PNS) on the
      proliferation of hematopoietic progenitor cells (HPC) in mice with immune
      mediated aplastic anemia. METHODS: Balb/c mice model of immune-mediated aplastic
      anemia was established by radiation with sublethal dose of 60Co following the
      intravenously infusing lymphocytes of DBA/2 mice. Model mice in the treated
      groups were treated separately with high, middle and low dose of PNS, 3.2 mg, 1.6
      mg and 0.8 mg per day respectively by intraperitoneal injection. Model mice in
      the control group and normal mice in the normal control group were treated with
      normal saline. The peripheral white blood cell (WBC) count and pathological
      examination of bone marrow were carried out 12 days later, the bone marrow was
      taken to be incubated in semi-solid culture system for observing proliferation of
      HPC. RESULTS: PNS could (1) increase peripheral WBC count: as compared with that
      in the model control, WBC in the high, middle and low dose PNS groups was raised
      by (34.3 +/- 2.9)%, (29.2 +/- 1.7)% and (14.5 +/- 1.6)% respectively, P < 0.01
      and P < 0.05; (2) improve the bone marrow inhibition: pathological examination
      showed in the model group, the hematopoietic structure was destroyed and replaced
      by fatty tissue, while in the PNS treated groups, the structure of marrow was
      rather complete and filled with abundant hematopoietic cells; (3) promote the
      proliferation of HPC: as compared with the model group, the colony formation of
      CFU-GM were increased by (64.4 +/- 2.8)%, (67.3 +/- 2.4)% and (21.9 +/- 1.8)%
      respectively and that of CFU-E increased by (31.9 +/- 3.6)%, (20.7 +/- 2.4)% and
      (12.8 +/- 2.6)% respectively in the three PNS treated group (P < 0.01 and P <
      0.05). CONCLUSION: PNS could enhance hematopoiesis by promoting proliferation of
      CFU-GM and CFU-E progenitors so as to improve the hematopoietic function in mice
      of immune-mediated aplastic anemia.

PMID- 14571618
TI  - [Effects of bushen tongmai recipe on insulin signaling in insulin resistant
      rats].
AB  - OBJECTIVE: To investigate the effect of Bushen Tongmai recipe (BSTMR) on the
      tyrosine phosphorylation of insulin receptor (InsR) and insulin receptor
      substrate-1 (IRS-1) after insulin stimulation in muscle and fat tissues of
      insulin resistant (IR) rats induced by high-fat forage. METHODS: Male Wistar rats
      were randomly divided into normal group (normal forage), model group (high fat
      forage, in which 61% calories were supplied by fat) and treated group (same
      forage as model group and treated with BSTMR). All animals were fed for 8 weeks,
      fasting blood glucose (FBG), blood glucose (BG) levels 1- and 2-hrs after glucose
      loading were determined routinely, serum fasting insulin (Ins) was determined
      with radioimmunoassay (RIA) and tyrosine phosphorylation level of InsR and IRS-1
      in fatty and muscular tissues was measured by immunoprecipitation and Western
      blot. RESULTS: Compared with the model group, FBG in the treated group changed
      insignificantly, but level of Fins decreased markedly (P < 0.01), so the insulin
      sensitivity index was significantly elevated in the treated group (P < 0.01),
      levels of BG 1- and 2-hrs after glucose loading in the treated group were greatly
      improved in comparison with those in the model group (P < 0.05 and P < 0.01
      respectively). Meanwhile, the density of electrophoresis bands of tyrosine
      phosphorylated InsR and IRS-1 proteins in muscular and fatty tissues in the
      treated group increased obviously. CONCLUSION: BSTMR could attenuate the insulin
      resistance in rats, its pharmaceutical mechanisms might be closely related with
      the elevation of the tyrosine phosphorylation levels of InsR and IRS-1 in
      muscular and fatty tissues after insulin stimulation, and improvement of insulin
      signal transduction in target tissues.

PMID- 14571619
TI  - [Study on establishment of Alzheimer's disease animal model and intervening
      effect of zhinao capsule on it].
AB  - OBJECTIVE: To establish an experimental animal model of Alzheimer's disease (AD)
      with clinical and pathological specificity conformed to AD in human, and to
      observe the effect of Zhinao Capsule (ZNC) on learning, memory and patho
      morphological parameters in the model. METHODS: The experimental AD model of rats
      was improved and established by combined injection of beta-amyloid protein (beta
      AP) to lateral ventricle and transforming growth factor beta 1 (TGF beta 1) to
      brain. The learning and memory function of the model rats were tested by step
      through test and water-maze test, and the number and cross area of beta-AP
      deposited macula in cerebral cortex and CA1 region of hippocampus were estimated
      quantitatively using immunohistochemical method and image pattern analysis.
      RESULTS: The improved AD animal model showed both the specificity of behavior
      (learning and memory impairments) and the typical pathological specificity (beta
      AP deposited macula). ZNC could effectively improve the impairment of learning
      and memory and reduce the number and cross area of beta-AP deposited macula in
      cerebral cortex and hippocampus CA1 region in the AD model rats. CONCLUSION: The
      AD rat model induced by the combined injection of beta-AP and TGF beta 1 is a
      good animal model simulated to the clinical reality, which could be used to
      screen and evaluate the anti-dementia agents. ZNC could display anti-dementia
      effect of the AD model rats.

PMID- 14571620
TI  - [Effects of langchuangjing granule on apoptotic of CD4+ T and CD19+ B in spleen
      of BXSB mice with systemic lupus erythematosus].
AB  - OBJECTIVE: To study the effect on apoptotic of CD4+ T, CD19+ B in spleen of BXSB
      mice with systemic lupus erythematosus treated with Langchuangjing Granule and to
      probe into the mechanism of treatment. METHODS: The apoptosis was examined by the
      flow cytometric analysis and immunofluorescence double-staining method. RESULTS:
      Apoptosis of male BXSB mice speeds up. Langchuangjing Granule can restrain the
      excessive apoptosis of CD4+ T and CD19+ B cells in spleen. CONCLUSION:
      Langchuangjing Granule treated systemic lupus erythematosus by restraining the
      excessive apoptotic of T, B lymphocytes, probably restraining the release of
      excessive amount of apoptotic DNA fragments, so decreasing abnormal proliferation
      of B cells and the produce of autoantibodies.

PMID- 14571621
TI  - [Effect of Chinese herbal medicine for nourishing yin and purging fire on mRNA
      expressions of gonadotropin-releasing hormone and its receptor in precocious
      puberty model rats].
AB  - OBJECTIVE: To probe the mechanism of Chinese herbal medicine (CHM) for nourishing
      Yin and purging Fire on the expressions of gonadotropin-release hormone (GnRH)
      and its mRNA expression in hypothalamus and GnRH receptor mRNA in pituitary in
      danazol induced precocious puberty model rats. METHODS: Rats were divided into
      the normal group, the model group, the blank control group and the CHM group.
      Rats, except that in the normal group, were subcutaneously administered danazol
      300 micrograms at 5 days of age individually and CHM was fed to rats in the CHM
      group from 15 days of age, in the meantime, normal saline was fed to rats in the
      blank control group. Expression of GnRH in hypothalamus was observed by
      immunohistochemical method and expressions of GnRH mRNA in hypothalamus and GnRH
      receptor mRNA in pituitary were determined by RT-PCR. RESULTS: Compared with rats
      in the normal groups, the vaginal opening and the onset of first estrus were
      ahead of time, the number of GnRH immunoreactive positive cells decreased and the
      expressions of GnRH mRNA in hypothalamus and GnRH receptor mRNA in pituitary up
      regulated in the model rats and blank control rats. Compared with the model and
      the blank control groups, in CHM group, all the above-mentioned abnormally
      changed parameters improved significantly after treatment. CONCLUSION: CHM for
      nourishing Yin and purging Fire may inhibit the abnormal hyperfunction of
      hypothalamus-pituitary-ovary axis in precocious puberty rat induced by danazol
      via reducing the synthesis and release of GnRH, and lowering the responsibility
      of pituitary cells to GnRH. This may be the primary mechanism of CHM in
      effectively treating the true precocious puberty.

PMID- 14571622
TI  - [Clinical observation on treatment of linguopapillitis with xinhuang tablet,
      resina dracaenae and xuekang capsule].

PMID- 14571623
TI  - [Observation on effect of integrative Chinese and Western medicine in treating
      acute attack of bronchial asthma].

PMID- 14571624
TI  - [Drug induced suffering for the aged and rational usage on Chinese drugs].

PMID- 14571625
TI  - [Some thoughts on treatment of hypertension by traditional Chinese medicine].

PMID- 14571626
TI  - [Current state and prospects of sero-pharmacological study on extracorporeal anti
      tumor effects of Chinese herbal medicines].

PMID- 14571627
TI  - Attending to the spiritual side of cardiac patients.

PMID- 14571628
TI  - Palliative psychiatric nursing care. An emerging role?

PMID- 14571629
TI  - Do atypical antipsychotic agents have a role in the treatment of depression?

PMID- 14571630
TI  - Group therapy for male batterers. Comparison of cognitive-behavioral & object
      relations approaches.
AB  - Domestic violence is the silent epidemic in America's households, and batterers'
      recidivism rates are staggering, despite court-mandated treatment found in every
      state. This article compares and explores cognitive-behavioral and object
      relations theories, beginning with an overview of the conceptualization of
      intimate rage from each approach. In addition, the espoused treatment approaches
      for each theory are examined.

PMID- 14571631
TI  - The professionalization of psychiatric nursing. From doctors' handmaidens to
      empowered professionals.
AB  - The professionalization of psychiatric nursing in the United States has been
      subject to political, economic, and theoretical influences, and prominent
      individuals such as Florence Nightingale and Hildegard Peplau have caused changes
      over time. Throughout history, professional and societal beliefs about mental
      illness have affected the nature of psychiatric nursing. In colonial times,
      people with mental illnesses were considered to be either possessed by demons or
      inferior and treated as animals. Today, psychobiological causes of mental illness
      are better understood, and treatment is aimed at adjusting disordered physiology
      and implementing psychosocial interventions. Care of people with mental illnesses
      has echoed this shift with increasing professionalization of psychiatric nurses.
      Attention to the lessons of history can help psychiatric nurses identify current
      societal influences, act on them according to their own vision, and further
      increase their professionalism.

PMID- 14571632
TI  - Early psychosocial and pharmacological interventions after traumatic events.
AB  - 1. There is no evidence to suggest that routine provision of single-session
      psychological interventions after traumatic events prevents the development of
      psychological sequelae. Some such evidence exists regarding multiple-session,
      cognitive-behavioral interventions. 2. There is no evidence to suggest that
      routine use of pharmacological agents prevents development of psychological
      sequelae in traumatized individuals. 3. Given the current evidence base,
      development of stepped-care programs focusing on education, screening, and
      treatment is warranted. 4. Currently, the main role of mental health
      professionals early on is to ensure emotionally supportive systems of care are in
      place, which will help identify individuals who appear most distressed so
      evidence-based interventions can be offered.

PMID- 14571633
TI  - [Difficult hypertension control with treatment].

PMID- 14571634
TI  - [Causes of uncontrolled hypertension. DUO-HTA survey].
AB  - OBJECTIVES: To identify the socio-demographic, clinical, psycho-behavioural and
      therapeutic factors explaining uncontrolled blood pressure in a population of
      hypertensives in ambulatory practice. METHODS: The DUO-HTA survey is a national,
      cross-sectional, mirrored, observational study, from a representative sample of
      347 general practitioners (MG) and 210 cardiologists, and a population of 2022
      hypertensive patients followed by these doctors. The data were collected by means
      of questionnaires completed by the hypertensives and their doctors. RESULTS: The
      factors significantly discriminating patients for whom BP was controlled (C) from
      those patients whose BP was not controlled (NC) were an age less than 65 years,
      smoking, obesity, alcohol consumption, sedentary lifestyle and multiple anti
      hypertensive treatment. On the psycho-behavioural front, the NC patients were
      more often anxious and irritable, claiming to lead a stressful life and for whom
      hypertension was often perceived as a "foreign entity" and a source of
      frustration and multiple deprivations. The factors discriminating the NC doctors
      from the C doctors were essentially psycho-behavioural, with the NC doctors
      considering the management of hypertension as being less gratifying, and
      hypertension as a condition with fluctuating progression, poorly understood and
      dramatized by patients. CONCLUSION: The DUO-HTA survey underlines the weight of
      reciprocal representation systems in hypertension for patients and their doctors,
      as well as the quality of the doctor-patient relationship in blood pressure
      control. It prompts the development of sensitisation actions for practitioners
      centered on improving the doctor-patient relationship.

PMID- 14571635
TI  - [Prevalence and management of patients with a prior history of atherothrombotic
      disease in primary care in France. Results of the ECLAT1 survey].
AB  - This cross-sectional study assessed the prevalence of subjects with a previous
      history of atherothrombotic disease (myocardial infarction, ischemic stroke
      and/or lower limb arterial disease) among patients treated in general medicine. A
      random sample of 3,009 French general practitioners was recruited. Patients who
      consulted one of these general practitioners on December 7th 2000 were included.
      Those with a previous history of atherothrombotic disease were identified and
      further data on their cardiovascular risk factors and drug use were collected.
      The prevalence of patients with a previous history of atherothrombotic disease
      was 2% [95% confidence interval: 1.9-2-1] in subjects younger than 65, 13.4%
      [12.7-14.2] between 65 and 74 and 17.0% [16.2-17.8] in subjects older than 74.
      Arterial hypertension was found in 62.2% of the patients with a previous history
      of atherothrombotic disease, overweight or obesity in 59.4%,
      hypercholesterolaemia in 55%, current or past smoking in 48.3%, and diabetes
      mellitus in 20.1%. The last blood pressure and LDL-cholesterol measurements were
      respectively higher than or equal to 140/90 mmHg and 3 mmol/l in 70.6% of the
      patients suffering from arterial hypertension (missing data in 2.2%) and in 48.2%
      of the patients suffering from hypercholesterolaemia (missing data in 31.4%).
      Atherothrombosis represents a significant part of the primary care activity in
      France. Despite a widespread antihypertensive and hypocholesterolaemic drug
      prescription, the control of cardiovascular risk factors is insufficient. The
      high prevalence of overweight may contribute to this poor control.

PMID- 14571636
TI  - [Application of risk stratification scores in acute myocardial infarction.
      Results of RICO (observation of infarction in the Ivory Coast)].
AB  - Several risk stratification scores for myocardial infarction have been developed
      in recent years, based on clinical trials. The object of this study was to assess
      the application of these scores in an unselected population of myocardial in
      farction in a French department. One thousand and fifty-four patients with acute
      myocardial infarction were included in the RICO observatory in the Cote d'Or.
      Those with ST elevation (SST), N = 746, had 30 day-mortality rates which
      increased with the TIMI and GUSTO scores (khi2 tendency, p < 0.001). There was a
      good discriminatory power of both these scores (correlations of 0.71 and 0.69
      respectively). Similarly, logistic regression analysis showed a significant
      relationship between TIMI and GUSTO scores and 30 day mortality (p < 0.001). No
      correlation was observed between mortality and increased TIMI score in cases of
      infarction without ST elevation, N = 308, p = 0.344. Moreover, this score had a
      low discriminatory value in the study population with a correlation of 0.54. On
      the other hand, regression analysis showed a strong predictive value of the
      PURSUIT score in infarction without ST elevation for mortality. In addition,
      there was a correlation between death and the value of this score (p < 0.05).
      This score also showed a good discriminatory power with a correlation of 0.71.
      This study shows that, in an unselected population, risk stratification scores
      may be used as a routine in myocardial infarction, especially in cases with ST
      elevation.

PMID- 14571637
TI  - [Value of Doppler indices of diastolic left ventricular dysfunction in acute
      cardiac insufficiency].
AB  - OBJECTIVE: To examine the prevalence of diastolic dysfunction by Doppler study in
      acute cardiac failure. CONTEXT: A recent study showed that diastolic dysfunction
      is constant in stable cardiac failure with preserved systolic function and
      suggested that its measurement was not necessary for the diagnosis of diastolic
      cardiac failure, but the prevalence of diastolic dysfunction in acute cardiac
      failure is not known. METHOD: The mitral and pulmonary venous profiles, the
      propagation velocity Vp of colour filling flow, and the lateral velocity Ea of
      the mitral ring in DTI were studied at the time of treatment initiation in 28
      patients in sinus rhythm and in acute cardiac failure (11 NYHA IV and 17 with
      pulmonary oedema), of whom 18 had an ejection fraction greater than 50%. RESULTS:
      Diastolic dysfunction was present in the combined study of mitral and pulmonary
      profiles in 95% and 100% respectively of patients in cardiac failure with
      preserved systolic function and altered systolic function, and Vp < 45 and/or Ea
      < 8 cm/s was observed in 55% and 100% respectively of these patients. At
      respective pathological threshold values of 1.5 and 10, the combined indices E/Vp
      and E/Ea were concordant with the evaluation of filling pressures in 83% of
      patients with preserved systolic function and 100% of the systolic cardiac
      failure cases. CONCLUSION: Diastolic dysfunction is almost constant in acute
      cardiac failure independently of the ejection fraction value. However, normal
      values of Ea and Vp do not exclude the diagnosis of diastolic cardiac
      insufficiency in the acute situation.

PMID- 14571638
TI  - [Silent ischemia and acute cardiac insufficiency with normal systolic function:
      diagnostic value of troponin I measurement].
AB  - The physiopathological mechanisms resulting in increased left ventricular
      pressures in acute cardiac failure with normal systolic function are not well
      understood. Although coronary artery disease is commonly associated with acute
      episodes, the diagnostic value of troponin I measurement and the prevalence of
      ischaemia as the predisposing factor are not known. Twenty coronary patients
      (mean age 77 +/- 9 years) in acute cardiac failure with left ventricular ejection
      fractions of 50% or over and without angina, were studied retrospectively. The
      diagnostic value of troponin I (cTnI, AxSYM, method) was assessed by comparing
      with a control group of 16 acute cardiac failure patients without coronary
      disease. The frequency of hypertension and diabetes in the coronary group was 50
      and 45% respectively. At the time of investigation, the pulmonary capillary and
      systemic arterial pressures were comparable in the coronary patients irrespective
      of the cTnl value. At threshold levels of 0.5 microgram/l, cTnl had a specificity
      of 100% and confirmed ischaemia in 60% of the coronary patients. Ischaemia was
      the commonest predisposing factor for increased cardiac pressures. Over a 268 +/-
      101 days follow-up period, half the coronary patients were readmitted for acute
      cardiac failure and a third of them died. The authors conclude that silent
      ischaemia is a common predisposing factor for acute cardiac failure in coronary
      patients with normal systolic function and troponin I measurement is a useful
      diagnostic help.

PMID- 14571639
TI  - [Impact of advances in transthoracic imaging on the indications for
      transesophageal echocardiography].
AB  - Technical advances have considerably improved the quality of imaging by
      transthoracic echocardiography in recent years. This has allowed access to
      information formerly reserved for transoesophageal investigation. As a result,
      certain changes in the indications of transoesophageal echocardiography have come
      about in clinical practice. The best example is probably in the evaluation of
      mitral regurgitation. The possibilities of accurate description of mitral valve
      anatomy and of reliable quantification of the lesion have reduced the indications
      of transoesophageal echocardiography in this pathology. In other indications,
      such as suspected endocarditis, the investigation of systemic embolism or
      dissection of the aorta, transoesophageal echocardiography is irreplaceable but
      the additional information obtained compared with transthoracic echocardiography
      is less.

PMID- 14571640
TI  - [Calcified aortic stenosis with left ventricular dysfunction and low
      transvalvular gradients. Must one reject surgery in certain cases?].
AB  - The natural history of severe aortic stenosis (aortic valve area < 1 cm2 or < 0.6
      cm2/m2) with left ventricular systolic dysfunction and low transvalvular
      gradients (mean gradient < 40 mmHg) is mediocre in the short term and the
      operative risk is high. Dobutamine echocardiography provides a reliable
      evaluation of the aortic obstacle by diagnosing the rare cases of relative aortic
      stenosis in which the valve surface area has been underestimated because of a low
      cardiac output (aortic surface area > 1.2 cm2 with a mean gradient < 30 mmHg with
      dobutamine): in this case, the limited available data suggests that medical
      therapy with strict follow-up of its efficacy is the best management. The other
      use of dobutamine echocardiography is to assess left ventricular contractile
      reserve, defined as a increase > or = 20% in stroke volume under dobutamine.
      Cases with a contractile reserve have an operative risk of 5 to 10% and the
      medium-term benefits of valve replacement have been demonstrated. In the absence
      of contractile reserve, the operative risk is much grater, 30 to 60%, and also
      depends on other parameters such as the mean basal transaortic pressure gradient
      (risk five times greater in cases with a mean gradient < 20 mmHg), the need for
      coronary bypass surgery and associated co-morbid conditions. The surgical
      contraindications are in fact relatively few and concern patients with several
      risk factors: absence of contractile reserve itself is not a definitive surgical
      contraindication.

PMID- 14571641
TI  - [Value and indications of transesophageal echocardiography before cardioversion
      of atrial fibrillation].
AB  - Transoesophageal echocardiography is essential for the diagnosis of left atrial
      thrombosis and its precursors (dense spontaneous contrast--reduced auricular
      emptying velocities) and for the diagnosis of complex aortic atheroma. The
      sensitivity and specificity of transoesophageal echocardiography for the
      diagnosis of left atrial thrombus are about 100% and about 90% for that of aortic
      atheroma. The formal indications for transoesophageal echocardiography before
      cardioversion are: atrial fibrillation complicated by stroke or a recent systemic
      embolism: atrial fibrillation complicated by mitral valve disease as the thrombo
      embolic risk is major in this context: atrial fibrillation with a high
      thromboembolic risk: a history of stroke, presence of cardiac failure, diabetes,
      permanent hypertension, a very dilated left atrium (> or = 50 mm): apparently
      isolated atrial fibrillation for which long term anticoagulant therapy is hoped
      to be avoided. On the other hand, in recent, uncomplicated, non-valvular atrial
      fibrillation, a common fallacy should be corrected: transoesophageal
      echocardiography does not improve the safety of electrical cardioversion. With
      similar durations of prior anticoagulant therapy. Over a 3 week period, the
      frequency of thromboembolic complications is the same whether or not
      transoesophageal echocardiography is performed before cardioversion (0.8% in both
      groups of the SEIDL study). With short periods of anticoagulant therapy before
      cardioversion, there is a higher thromboembolic complication and mortality rate
      (ACUTE study). The safety of cardioversion is not related to the practice of
      prior transoesophageal echocardiography but to strict and efficacious
      anticoagulation for a period of 3 weeks before cardioversion.

PMID- 14571643
TI  - Diastolic heart failure: old story, new concepts.
AB  - Diastolic heart failure refers to a clinical syndrome characterised by symptoms
      and signs of congestive heart failure, with a normal or subnormal left
      ventricular (LV) systolic function associated with alterations in LV diastolic
      function. Diastolic dysfunction is a pathological condition during which the LV
      is unable to accept a volume of blood coming back from the lungs appropriate to
      maintain its stroke volume under normal filling pressure. Three eventually
      associated mechanisms are responsible for such dysfunction: impaired LV
      relaxation, increased LV stiffness and loss of normal atrial function. Prevention
      of LV hypertrophic remodelling should decrease the incidence of diastolic heart
      failure.

PMID- 14571642
TI  - [Cardiac surgery in the octogenarian: what risks for what benefits?].
AB  - About 1 to 8% of patients referred for cardiac surgery in industrialised
      countries are octogenarians. Hospital mortality is high and depends on age, type
      of surgery and other predictors of death which are female gender, left congestive
      heart failure, history of myocardial infarction, chronic obstructive lung
      disease, renal insufficiency, carotid and others vascular diseases. Morbidity is
      also very high. Besides supraventricular arrhythmias, respiratory failure is the
      main cause (20 to 30%) of morbidity, followed by cerebrovascular accident and
      renal failure. Due to this high rate of postoperative events, the length of stay
      is significantly increased. At follow-up however, excellent functional status and
      survival rate is afforded by the operative procedure. The main problem remains
      the selection of patients in order to improve results.

PMID- 14571644
TI  - Hypertension and the microcirculation.
AB  - A large part of the changes in peripheral resistances associated with
      hypertension involves changes in the microvascular network. From the brief review
      presented here, it appears that arterioles' functional characteristics are
      largely modified in hypertension. Sensitivity to numerous vasoconstrictive
      substances is increased. Local angiotensin-converting enzyme activity is
      considerably higher. Endothelium-dependent dilation is reduced. Myogenic
      responses are also amplified by mechanisms dependent on both prostanoids and
      endothelin. Oxidative stress has been recently demonstrated to be an important
      pathophysiological mechanism of these alterations. Changes also affect the
      structure of the microvascular network. Morphological alterations in the
      arteriolar wall are not observed for all types of hypertension. Conversely,
      arteriolar and capillary rarefaction appears to be the changes affecting the
      structure of the microvascular network which are most often found. This led us to
      consider that the microvascular network should not only be considered as one of
      the putative mechanisms responsible for increased blood pressure but also as a
      key target for hypertension. Consequently, hypotensive drugs should also be
      tested and differentiated as regards their efficiency to prevent or to reverse
      the microcirculatory damage associated with hypertension.

PMID- 14571645
TI  - Place of beta 3-adrenoceptors among other beta-adrenoceptor subtypes in the
      regulation of the cardiovascular system.
AB  - Knowledge of the sympathetic system is a basic element in the understanding of
      numerous physiological and physiopathological phenomena. In the two last decades,
      new pharmacological, biochemical and molecular tools have changed our approach to
      the roles of beta-adrenoceptors in the cardiovascular system. In the heart, the
      positive inotropic effect of predominant beta 1-adrenoceptor stimulation is
      classically recognised. Several studies reveal a significant physiological
      relevance of the beta 2-adrenoceptor which could activate different signalling
      pathways in addition to that of cAMP. Moreover, the detection of a third beta
      adrenoceptor subtype, beta 3, in human heart, responsible for a negative
      inotropic effect through a NO signalling pathway, has changed the classically
      admitted paradigm on the regulation of heart function by the beta-adrenergic
      system. The identification of atypical beta-adrenoceptors, based on
      pharmacological tools, led to the discovery of "putative" beta 4-adrenoceptors,
      which constituted a low affinity state of the beta 1-adrenoceptors. In vessels,
      all beta-adrenoceptors subtypes, beta 1, beta 2 and beta 3, mediated a
      vasodilation, but the signalling pathway involved in this effect was variable
      according to their localization (endothelial or smooth muscle cells), the species
      and the vascular bed. beta-adrenoceptors are involved in several cardiovascular
      disease and could constitute a determinant therapeutic target. The efficiency of
      some beta-blockers used in the treatment of heart failure could result from
      action on beta 3-adrenoceptors. Moreover, a mutation of the beta-adrenoceptor
      subtype suggested a role in hypertension and diabetes mellitus.

PMID- 14571646
TI  - [Dyspnea of effort with an unusual cause: diagnostic significance of stress
      echocardiography].
AB  - Left intra ventricular obstruction occurring during doubutamine stress echography
      is not exceptional but its clinical significance is controversial, notably due to
      the non-reproducibility of such a phenomenon during physical exercise in a
      certain number of patients. Moreover, in the studies which demonstrate a link
      between symptoms of effort and left intra ventricular obstruction during
      dobutamine echography, an echography with effort was not systematically performed
      in order to confirm this relationship. We describe the case of two patients, aged
      50 and 62 years respectively, with no notable cardiovascular past history except
      hypertension, who had dyspnoea of effort in the absence of underlying cardiopathy
      in resting conditions. Dobutamine stress echography provoked a systolic anterior
      movement of the mitral valve (SAM) responsible for mitral insufficiency and
      significant left intra ventricular obstruction (maximum gradient of 77 mmHg for
      one, 130 mmHg for the other), with reproduction of spontaneous symptoms, in the
      absence of myocardial ischaemia. An effort echography performed several weeks
      later confirmed these data, even though a sublingual trinitrate (0.3 mg) test was
      without effect. In the absence of underlying hypertrophic cardiomyopathy the SAM
      (with left intra ventricular obstruction and mitral insufficiency) occurring
      during dobutamine stress echography could have clinical significance in selected
      cases, notably in hypertensive patients with effort intolerance who have normal
      systolic and diastolic function in the resting state, and absence of myocardial
      ischaemia during stress, as illustrated in our two observations. The therapeutic
      implications are clear, with patients like this successfully treated with beta
      blockers.

PMID- 14571647
TI  - [Cardiac effects of dermatomyositis. A case report].
AB  - The cardiac effects of dermatomyositis and polymyositis are found frequently at
      autopsy, even though the clinical manifestations are rare. We report the
      observation of a patient with dermatomyositis, in whom ventricular tachycardia,
      and dilated hypokinetic cardiomyopathy were in the foreground of the cardiac
      anomalies. This rhythm disturbance responds to treatment, as opposed to the
      associated dilated cardiomyopathy. Electrocardiographic anomalies are frequent,
      notably conduction disturbances. Ventricular rhythm disturbances are of poorly
      defined frequency. Cardiac insufficiency is often stabilised with treatment. The
      other effects are much rare.

PMID- 14571648
TI  - [Cardiobacterium hominis endocarditis. A case report].
AB  - We report the case of a Cardiobacterium hominis endocarditis causing an acute
      mitral insufficiency complicated of left heart failure. The patient has been
      treated after a few days by surgical valvuloplasty. Cardiobacterium hominis is a
      bacteria of the HACCEK group, bacille gram-negative, sometimes anaerobic,
      difficult to isolate. Recently, Polymerase Chain Reaction analysis appears to be
      effective for the the diagnosis in the identification of fastidious micro
      organisms like Cardiobacterium hominis. We have reviewed in the literature 71
      cases of Cardiobacterium hominis endocarditis; clinical presentation is often sub
      acute, the bacteriological diagnosis is based on hemocultures for which the
      culture is slow and require enriched environments. Hemodynamic and thrombo
      embolic complications are frequent because of the high pathogenicity of the
      bacteria which provides big and friable vegetations. Despite a high sensibility
      to antibiotherapy, surgical intervention is often required.

PMID- 14571649
TI  - Speech recognition tests in sensorineural hearing loss.
AB  - The ability to understand speech must be considered the most important measurable
      aspect of human auditory function. Due to the innovative developments in hearing
      aids and cochlear implants, there has been a renewed interest in speech
      recognition testing. During recent years, the start of several multi-centre
      studies have increased the urge to come to some consensus on the use of different
      speech materials. In this article a global overview of existing types of speech
      material in Dutch will be given. For each type, there is a reference to similar
      speech audiometric tests in French, English and German.

PMID- 14571650
TI  - Airbags and permanent auditory deficits. A real correlation?
AB  - OBJECTIVES: To evaluate the relationship between airbag-induced noise and
      individual metabolic risk factors in determining persistent hypoacusia in drivers
      after road accidents. METHODOLOGY: We selected 22 patients previously involved in
      a car accident with deployment of airbags. Patients underwent general and
      audiological clinical history, tonal audiometric examination, vocal audiometric
      examination, impedance meter examination and blood tests. RESULTS: We divided
      patients, according to audiometric data, into 2 groups: group A with no residual
      otological disturbances (6 subjects) and group B with persistent hypoacusia (16
      subjects). Blood parameters were into physiological levels in all group A
      patients; on the contrary 12 (subgroup B1) out of 16 group B patients had altered
      blood levels of glucose, urea and cholesterol, with mean values of 155.8 +/- 38.6
      mg/dl, 48.2 +/- 8.3 mg/dl and 250.8 +/- 28.1 mg/dl, respectively, revealing
      statistically significant differences in these parameters when compared with the
      other 4 hypoacusic cases (Sub-group B2) and with the normal subjects (Group A) (p
      < 0.01 for glucose, p < 0.05 for urea and p < 0.001 for cholesterol).
      CONCLUSIONS: Our findings confirm the transitory otological damage due to airbag
      deployment: the intensity of the acoustic wave hitting the ear after airbag
      deployment is responsible for a temporary rise in the acoustic threshold but the
      persistence of an auditory deficit can be due to co-factors able to interfere
      with the acute acoustic trauma recovery processes through a metabolic,
      angiopathic, neuropathic or unknown mechanism. Moreover, also the age of the
      patients could affect in a significant way the recovery from the acoustic trauma.

PMID- 14571651
TI  - Tympanoplasty without skin incision of the external auditory canal: preliminary
      results.
AB  - INTRODUCTION: Most tympanoplasty techniques require skin incision of the external
      auditory canal. This step is not without morbidity and postoperative
      complications such as delayed healing, granulation tissue, lateralization,
      blunting and iatrogenic cholesteatoma. For small or midsize non-marginalized
      tympanic membrane perforations of the posterior or inferior quadrants, a
      transmeatal approach without incision of the cutaneous epidermis of the external
      auditory canal can theoretically offer advantages such as rapid healing and
      reduced postoperative complications. In this paper we present the preliminary
      results of a tympanoplasty technique with a retroauricular approach without skin
      incision of the canal and an overlay graft. MATERIALS AND METHODS: We performed
      10 tympanoplasties without skin incisions for small or midsize non-marginalized
      perforations, which do not exceed one third of the tympanic membrane surface,
      located in the inferior or posterior quadrants. RESULTS: With a minimum follow up
      of 3 months all patients showed excellent anatomical results without
      complications. Nine of them closed their average air bone gap at less than 10 dB.
      CONCLUSION: When anatomically feasible, our technique combines a post auricular
      approach and the absence of skin incision. It ensures rapid healing, preserves
      the anatomy of the eardrum and external auditory canal and reduces the risk of
      blunting and lateralization phenomena. The main difficulty concerns the cleavage
      of the epidermal and fibrous layer.

PMID- 14571652
TI  - Tympanoplasty using conchal cartilage graft.
AB  - Cartilage has been used successfully as a graft in middle ear surgery. It used to
      be reserved for advanced pathology because of its possible detrimental effect on
      postoperative hearing. Recent papers however failed to prove this effect. The
      present study describes the authors' experience in 161 cases of conchal cartilage
      tympanoplasty. In tympanoplasty type I postoperative pure tone average air-bone
      gap was within 20 dB in 88.4% of the cases. If combined with ossiculoplasty when
      the stapes was intact, 72% was within 20 dB and when the stapes was absent, 54.5%
      was within 20 dB. Taking rate of the graft was 95.6% (154/161) with 22% (36/161)
      representing revision surgery. At present the author uses cartilage graft as a
      first choice in tympanoplastic procedures.

PMID- 14571653
TI  - Petrous bone fractures in children: risk of meningitis, and indication for early
      Cochlear implant?
AB  - The case of a 5 year old boy who had a right petrous bone fracture with right CSF
      otorrhea and deafness is reported. This child presented, three years after the
      trauma, a right side otitis media, complicated by meningitis and pneumococcal
      sepsis, which might have as consequence a left side deafness. The bilateral
      deafness and the early possibility for cochlear ossification made us decide
      rapidly on a cochlear implant. Benjamin was then operated for a left side
      cochlear implant 40 days after contracting meningitis. Two months later, this boy
      was able to understand a speech without lip reading. Current concepts in the
      management of petrous bone fractures with CSF otorrhea are reviewed in this
      report. We also discussed prophylactic attitudes to adopt to reduce the risk of
      post temporal bone fracture meningitis.

PMID- 14571656
TI  - Macrolides: more than just antibiotics?!
AB  - Macrolides are used primarily as antibiotics, but they may have other effects.
      This was first suggested after clinical experience showed that macrolides have an
      important therapeutic role some inflammatory airway diseases in which infection
      is not considered as an important etiologic factor. In vitro, ex vivo and in vivo
      experiments revealed that macrolides reinforce local defense mechanisms in the
      upper respiratory tract such as mucociliary clearance and epithelial
      impermeability. In addition, macrolides influence acute inflammation, by altering
      concentrations of cytokines and changing leucocyte functions. This paper aims to
      review the current knowledge on the non-antibiotic effects of macrolides on local
      defense mechanisms and acute inflammation in the upper respiratory tract.

PMID- 14571659
TI  - [Autonomy and decision making in medicine].

PMID- 14571654
TI  - Preservation of hearing in vestibular schwannomas treated by radiosurgery using
      Leksell Gamma Knife: preliminary report of a prospective Belgian clinical study.
AB  - INTRODUCTION: Radiosurgery is an alternative to the microsurgical resection of
      vestibular schwannoma (VS). Since its introduction, radiosurgery has been used in
      more than 8000 patients with VS worldwide and the long term tumor control rates
      are reported to be 86 to 100%. The aim of this study is to report our experience
      with Leksell Gamma Knife (LGK) radiosurgery in the management of VS and to
      evaluate the serviceable hearing preservation rate after one-year follow-up.
      MATERIAL AND METHODS: Between January 2000 and October 2002, 95 patients with
      unilateral VS underwent LGK radiosurgery at the University Erasmus Hospital of
      Brussels with the first worldwide installed LGK C. All patients in our series
      underwent evaluation with high resolution neurodiagnostic imaging including
      computed tomography and MRI, and clinical evaluation as well as audiological
      tests that included tonal and vocal audiometries. The Gardner Robertson (GR)
      classification is used to report the results of this study. We identified 48
      patients treated for VS with LGK, tested and retested with vocal and tonal
      audiometries by the same team, and followed for a minimum of one year. There were
      38 patients with previously untreated VS (9 grade I, 9 grade II, 20 grade III
      according to Koos) and 10 patients with postoperative evolutive residual tumor.
      RESULTS: Before LGK, 24 patients had serviceable (17 GR class I and 7 GR class
      II) hearing; 16 (67%) of these patients had preservation of serviceable hearing
      (Pure tone average < 50 db and Speech discrimination > 50%) at the one-year
      audiological follow-up. It was observed that 9 of the 17 GR class I patients
      (52.9%) maintained their level of audition and 14 of these (82.3%) preserved
      serviceable hearing. No deterioration of hearing occurred in the 7 patients with
      preradiosurgery radiosurgery nonserviceable hearing (GR class III) at the one
      year follow-up. One patient improved from GR class V to III after LGK. No patient
      developed trigeminal neuropathy and only one patient who had preradiosurgery
      facial nerve dysfunction experienced deterioration at one-year follow-up.
      CONCLUSIONS: In view of the high tumor control rate and excellent long-term
      cranial nerve preservation rates, LGK radiosurgery should now be considered as an
      excellent alternative strategy to microsurgery for the management of VS grade I
      to III as well as in cases of residual tumor after microsurgery. Compared to
      results obtained in centers with long-term experience, our data suggest that LGK
      radiosurgery is an efficient reproducible therapeutic approach that offers high
      rate of hearing preservation. This justifies the choice of radiosurgery as the
      first treatment option in VS.

PMID- 14571661
TI  - [Patient autonomy--legal status in Austria].
AB  - The so-called living will is also an object of controversy in the Austrian legal
      literature. Especially the question to what extent this kind of advance directing
      is binding for the physician, the patient's legal guardian and the court is not
      yet resolved. Whereas a majority of Austrian legal scholars is of the opinion
      that an advance refusal of treatment made with capacity simply survives any
      supervening incapacity, the author proposes that the irreversibly incompetent
      patient should basically be treated according to what is called an "objective
      standard".

PMID- 14571658
TI  - The yellow nail syndrome.
AB  - The yellow nail syndrome is a rare clinical entity which combines three main
      features: yellow discolouration of the nails, chronic lymphedema, and pleural
      effusion. Since 1994, chronic rhinosinusitis is associated in this syndrome. A
      lot of other pathologic conditions are often present. The most frequent are:
      bronchiectasis, recurrent pneumonia, pericardic effusion, humoral immunity
      deficiencies. Among the etiopathogeneses advocated, the more credible ones deal
      with changes of the lymphatic network with hypoplastic vessels leading to
      inadequate adaptation, after local damage of the tissues. When this syndrome is
      suspected on the basis of the examination of the nails, an extensive
      investigation (dermatologic, pneumologic, lymphographic, biologic) has to be
      launched to exclude underlying neoplasma, or autoimmune disease, frequently
      associated with this syndrome. The treatment is controversial and poorly
      effective. Vitamin A and E, Zn sulfate and itraconazole are drugs the most often
      advised. Spontaneous healing is reported in 30% of the cases. Endoscopic
      endonasal surgery in such cases, when the sinusal mucosa is involved, is
      controversial and its outcome is not yet documented.

PMID- 14571660
TI  - [Paternalism in medicine: illustrated by the example of fiber optic
      bronchoscopy].
AB  - The question of when and how it is permissible for a physician to take a
      paternalistic approach to a patient is discussed. In the introduction, the
      physician-patient relationship is presented based on the empirical example of
      fiberbronchoscopy. An attempt to define the term paternalism more precisely leads
      to the result that not only are patients who are very limited in their autonomy
      (e.g. psychiatric and intensive-care patients) treated paternalistically, but
      that the patient status as such leads to a certain degree of paternalism. The
      example given is interpreted in detail and the pragmatic attitude of the
      physician to the patient "object" is criticized. Finally, a demand is made that
      the physician-patient relationship be a partnership, in which the physician
      appeals to the patient's autonomic components, addresses and encourages them.
      This latter approach is seen as an alternative to paternalism.

PMID- 14571657
TI  - Solitary extramedullary plasmacytoma of the maxillary sinus. Case report.
AB  - Solitary extramedullary plasmacytomas are rare tumors that often affect head and
      neck region. Because of the non-specific associated symptomatology, they
      frequently are misdiagnosed. We briefly describe a 69-year-old woman who
      developed solitary plasmacytoma in the left maxillary sinus and was initially
      treated as having sinusitis. We also report the diagnostic work-up that is
      necessary to establish a correct diagnosis in such cases. This case highlights
      that an appropriate investigation for neoplastic disease should be performed in
      patients presenting with persistent symptoms that resemble those of sinusitis,
      especially if these do not resolve after conservative medical treatment.

PMID- 14571662
TI  - Advance directives for psychiatric patients? Balancing paternalism and autonomy.
AB  - Advance directives contain wishes and values, fears and refusals of competent lay
      people regarding medical interventions in future situations when they might lack
      communicative and decision-making capacities. However, these advance directives
      for medical, psychiatric and care interventions can very well be used to improve
      the care for patients in psychiatry and gerontopsychiatry and to provide
      individualized care and treatment. The development and use of advance-care
      documents in psychiatry, and the clinical and ethical appreciation and
      recognition of the wishes and values of those patients, represent a particularly
      difficult challenge to medical paternalism.

PMID- 14571655
TI  - Bacteriology of chronic suppurative otitis media in congolese children.
AB  - AIM: The study intended to identify bacteria active in the chronic suppurative
      otitis media and to determine their sensitivity to current antibiotics. METHODS:
      After clinical evaluation, middle-ear secretions were taken for bacteriological
      examination from 78 children meeting the inclusion criteria. All children with
      cholesteatoma and those with tumors occluding the ear canal were excluded.
      RESULTS: The most frequent isolated germs, in descending order frequency, were as
      follows: Proteus mirabilis (23%), Pseudomonas aeruginosa (22%), Citrobacter (20%)
      and Salmonella (5%). There were no cases of mixed flora. Ofloxacin was
      susceptible on all isolates. Neomycin, gentamicin and polymyxin B were
      susceptible on 96%, 83% and 67% of the isolates respectively. All isolates were
      resistant to amoxycillin. CONCLUSION: Peudomonas, Proteus and Citrobacter are the
      most common causes of chronic otitis media among children in our community of
      congolese children. Ofloxacin and neomycin are the most highly effective against
      most of the isolated germs, and are therefore recommended as the first line local
      treatment. Amoxycillin and chloramphenicol should be avoided.

PMID- 14571664
TI  - Euthanasia: killing as due care?
AB  - On 10 April 2001, the Netherlands was the first country to pass a law on the
      killing of patients at their request (euthanasia), which took effect on 1 April
      2002. Belgium followed and passed a euthanasia law on 16 May 2002, which took
      effect on 23 September 2002 and is even more liberal than the Dutch one.
      Physicians will be exempted from criminal liability provided they satisfy the so
      called 'due care criteria'. However, in medical history euthanasia has never been
      part of the medical duty of care. Instead, the goals of medicine have always been
      the relief of pain and suffering. The current article provides insights into the
      Dutch, Belgian and Oregon euthanasia and physician-assisted suicide practices and
      reflects upon some central medical and legal documents on the regulation of
      euthanasia and the provision of palliative care. Modern palliative care includes
      both the delivery of competent palliative skills and a virtuous attitude of
      compassionate caring about the terminally ill patient as an autonomous person.
      Here, the author rejects killing as due care and proposes a novel concept of
      'RAHME' (Aramaic: compassion, love, mercy), which calls for a holistically
      oriented concept where physicians act as companions to the terminally ill and
      dying patients.

PMID- 14571663
TI  - [Patient autonomy: from the clinical routine of an oncologic department].
AB  - Advance directives are an important help for physicians, patients and relatives
      when it comes to evaluating the patients wishes and preferences in the terminal
      phase of life. They also help to safeguard the patients right of self
      determination. When the directives are clearly expressed and of recent date, they
      should be accepted without question. At present, only a few patients make use of
      this right, and we doctors should be in future inform patients more often about
      it.

PMID- 14571666
TI  - [Fecal incontinence in elderly diabeteic patients].
AB  - Faecal incontinence is a challenging clinical condition in the elderly diabetic
      patient and has a significant impact on the overall quality of life, but is often
      neglected by the care giving professionals. Up to 22% of diabetic patients have
      faecal incontinence depending on the definition applied. Multiple factors are
      almost always involved in the pathophysiology of faecal incontinence, including
      physiological age-related changes, diabetic neuropathy, multimorbidity and
      polymedication. As for constipation, the use of a stepwise approach for the
      diagnosis of faecal incontinence is highly recommended. The verification of the
      diagnosis and underlying causes of faecal incontinence are important for
      improving the quality of life, as well as the employment of the appropriate
      therapy particularly in the case of the elderly diabetic patient. Treatment
      options include, in addition to an optimised blood sugar control, the use of
      conservative measures, bio-feedback therapy and surgical interventions.

PMID- 14571665
TI  - Honouring the age-old commitment to "the patient's good": the promise--and peril-
      of hospice.
AB  - In this article, the rise of hospice in the United States is examined and some of
      its important strengths and weaknesses are described. It is suggested that,
      despite the tendency to believe otherwise, hospice is not immune to a kind of
      alienation between patients and clinicians based on the absorption of doctors
      with biomedical conditions and their possible technological remedies, thus
      overlooking or ignoring the patient's good. To protect the age-old fiduciary or
      "trust" relationship between patients and clinicians requires a re-adjustment of
      current attitudes and practices--not just in the current cure-oriented health
      care of conventional medicine, but in the palliation-oriented health care of
      hospice as well. That is, it requires the development of attitudes and practices
      that foster a democratic, multidisciplinary process of shared decision-making and
      the adoption of a genuinely bio/psycho/social understanding and articulation of
      "the patient's good"--irrespective of where along the continuum of care patients
      and clinicians find themselves (5, 13).

PMID- 14571667
TI  - [Effectiveness and safety of rectal analgesic sedation in ambulatory pediatric
      surgery].
AB  - Purpose of the study was to evaluate efficacy and safety of conscious sedation in
      ambulatory pediatric surgery. During 50 settings 38 patients were administered
      0.75 mg/kg Ketamine and 0.4 mg/kg Midazolam rectally prior to the diagnostic or
      therapeutic procedure. Effects on vital signs, anxiolysis and pain reduction were
      documented. Side effects and complications were assessed. Satisfaction of
      patients and their parents were evaluated separately. Conscious Sedation can been
      administered safely by the physician, even in the absence of anesthesiological
      colleagues, as long as the correct indication is taken account of and only well
      established analgetics in standardised doses are given. Furthermore the
      intervention needs to take place in a well-organised setting. Advantages of the
      procedure are a cooperative patient with stable vital signs with the patients
      themselves and their parents profiting from stress-reduction through amnesia and
      effective pain management.

PMID- 14571668
TI  - [Epilepsy and the brain's morphological-functional organization].
AB  - The article summarized the results of long-term studies of the author with using
      experimental methods--creation of penicillin and aluminium epileptogenic foci,
      orbito-frontal cortex stimulation and elimination, and clinical investigation of
      epileptic status, prefrontal epilepsy, absence EEG activity, symptomatic rolandic
      epilepsy, childhood epilepsy. Based on the results obtained, the author
      formulates the conceptions on (1) the key role of prefrontal cortex in the
      antiepileptic defense system and motor activity control, (2) the role of slow
      activity in antiepileptogenesis, (3) the age-dependent rhythmic possibilities of
      children's brain, which determined age-dependent epilepsy types, (4) the
      complexity of between-hemispheric interactions in this disease.

PMID- 14571669
TI  - [Pathogenesis and therapy of posttraumatic epilepsy].
AB  - Considerations on prevalence, conditions and development mechanisms of epilepsy
      after cranio cerebral injuries as well as peculiarities of its diagnosis using
      clinical, neurophysiologic and computed tomography methods are presented.
      Implications and limitations of the latter, frequency and features of
      neurological and mental disorders in relation to main appearances of the disease,
      i.e. types of epileptic seizures, etc., are regarded. Principles of treatment of
      posttraumatic epilepsy, the data on biochemical, neurochemical and
      neuropathological symptoms of epileptogenesis are summarized. The authors
      highlighted the advantages of monotherapy, importance of taking into account the
      patient's personality, contacting with a patients family and ensuring his or her
      rights and quality of life. Also, the bases and stages of patient's
      rehabilitation are discussed.

PMID- 14571671
TI  - [Subjective body experience and therapy of somatoform disorders].
AB  - The article addresses the problem of subjective body experience in patients with
      somatoform mental disorders. Perspectives of multi-axial model of subjective body
      experience and methodical approaches to its descriptions are discussed. Different
      variants of body experience organization are described. Clinical peculiarities of
      somatoform mental disorders were closely connected with the complicated structure
      of body experience. Main processes involving body experience are those of self
      identification structuring: determination of the borders of subjectivity,
      relations with objects, representation of self-ego. An analysis of structure of
      subjective body experience enabled to work out differentiated psychotherapeutic
      approaches to complex rehabilitation of patients with somatoform mental
      disorders.

PMID- 14571670
TI  - [Electroclinical characteristics of Landau-Kleffner syndrome].
AB  - The study aimed at investigating epileptic attack's semiology and other
      electroclinical characteristics in Landau-Kleffner syndrome as well as
      therapeutic efficacy. Six patients with Landau--Kleffner syndrome, 5 boys, 1
      girl, aged 6-10 years, mean age 7.5 years, have been analyzed. Epileptic attacks
      were observed only in 3 patients with debut at the age of 2.5-6 years (mean 4
      years). In 50% of the cases, the attacks were not detected. The types of
      epileptic attacks were specified as follows: atypical absences--3 patients;
      pharyngo-oral--2; secondary generalized--2; atonic falls--1; hemiconvulsive--1.
      In routine EEG study, regional epileptiform activity was observed in all the
      patients, being localized in central temporal (3 cases), posterior temporal (1)
      and fronto-temporal (1) leads. In 3 cases (50%), diffusive epiactivity was also
      detected. During sleep, emergence of prolonged diffuse epiactivity was revealed
      for all the patients, with appearance of electrical status epilepticus during
      slow sleep in 50%. Valproates in dosage 30-60 mg/kg daily were highly effective
      for stopping epileptic seizures. Significant improvement of speech functions was
      observed only if antiepileptics sulthiame (ospolot) or clobasam (frizium) were
      used in addition to basic therapy. Clobasam in dosage 0.5-0.75 mg/kg daily was
      the most efficient in blockade of EEG diffuse epileptiform activity, reduction of
      aphasia symptoms and behavior improvement.

PMID- 14571672
TI  - [Results of surgical treatment of epilepsy with bilateral temporal lesions].
AB  - Nineteen patients with recurrence of paroxysmal syndrome after temporal focus
      resection and 37--after stereotaxic destruction of amygdala nuclei from both
      sides operated in the periods of 1967-1984 and 1989-1999, respectively, were
      studied. Duration of follow up study was from 1 to 35 years. The results of the
      study were compared to a level of patient's "real work-status" at the moment of
      examination. Dynamic postoperative EEG investigation revealed a number of focal
      activity features. Specifically, there were lost of leading focus signs, moving
      of intensive epileptogenesis focus to the opposite side or primary revealing of
      contralateral focus in different postoperative periods. Such patients are in need
      of anticonvulsive medicine because of possibility of a relapse within 2 or 6
      years after surgery. According to the results obtained, open surgical
      intervention in the leading epileptic focus (anterotemporal lobectomy) in
      patients with bilateral temporal foci seems to be inexpedient. One of the
      treatment methods is stereotaxic bilateral amygdalotomy.

PMID- 14571673
TI  - [The use of depakene and depakene-chrono in idiopathic generalized epilepsy].
AB  - During 5 years, 104 patients with different types of idiopathic generalized
      epilepsy were treated with depakine and depakine-chrono in monotherapy and
      polytherapy schedule. Thirty-three patients had childhood absence epilepsy, 34-
      juvenile absence epilepsy, 33--juvenile myoclonic epilepsy and 3--generalized
      convulsive seizures in wake up periods. Mean medication dose was 1200 mg daily.
      Significant improvement of the patient's state was revealed in 50% of the cases,
      being most efficient in patients with juvenile myoclonic epilepsy (60.6%) and in
      children absence epilepsy (57.5%). Indices of remission formation and quality
      changed in the same direction--complete remissions were more frequent in juvenile
      absence epilepsy. Depakine is concluded to be an effective medication for the
      treatment of idiopathic generalized epilepsy.

PMID- 14571674
TI  - [Topamax in the treatment resistance partial epilepsy].
AB  - Twenty-five epileptic patients, mean age 25.7 years, have been studied. Twenty
      two of them were diagnosed with symptomatic partial epilepsy, 1--with criptogenic
      partial epilepsy and 2--with idiopathic partial epilepsy. Illness duration was
      estimated as follows: above 5 years--5 patients, above 10 years--10, above 20
      years--4 and less than 5 years--6. Polymorphic seizures were detected in 56% of
      the cases and monomorphic ones, resistant to the previous traditional
      anticonvulsant therapy,--in 44%. Topamax was used as an add-on therapy to the
      previously prescribed anticonvulsants in initial dose of 25 mg daily, with a
      following continuous dose increase. The mean therapeutic dosage was 100 mg daily.
      Therapeutic efficacy was assessed during 3 months. Since 1 month of topamax
      adjunction to a treatment schedule, a mean frequency of all types of seizures was
      reduced. The best effect was found in the case of combination of simple partial
      and secondary generalized seizures. The medication was effective in 60-80% of the
      patients with strong resistance to traditional anticonvulsants. Topamax is
      concluded to be a highly effective antiepileptic medication, which gives new
      possibilities for a treatment of patients with partial epilepsy resistant to
      traditional drugs.

PMID- 14571675
TI  - [Dopamine receptor agonists in treatment of outpatient patients with Parkinson's
      disease].
AB  - The paper summarized an experience of pronoran (piribedil) treatment of 516
      patients with Parkinson's disease (primary parkinsonism) conducted in the
      district outpatient clinics of 7 Moscow administrative areas. In 84 cases, the
      medication was used as a monotherapy and in 432--in combination with levodopa
      contained drug madopar. An improvement of patient's state, with reducing of
      bradikinesia, tremor and rigidity, was achieved in 73.0 +/- 20.4% of the
      patients. Combined therapy allowed decreasing of madopar dosage in 58.5 +/- 16.7%
      of the patients. Pronoran (piribedil) is well tolerated. The authors recommend it
      for the treatment of outpatients with Parkinson's disease.

PMID- 14571676
TI  - [Behavioral therapy of ticks with negative reinforcement in children].
AB  - Thirty-two children suffering from motor and vocal ticks exhibited weakness and
      distonia of ticks-prone muscles were examined. Based on the results obtained
      earlier, a complex of physical exercises has been worked out and conducted for 20
      days. The patients were divided into 3 groups: 1st (n = 10) group did the
      exercises daily for training the ticks-prone muscles; the 2nd one (n = 10)
      exercised only after tick's appearance--negative reinforcement; 3rd group (n =
      12) did exercises after tick's appearance as well but on irregular basis-
      probable negative reinforcement. In the 1st group, the exercising resulted in
      muscle strengthening and decrease of tick's number. The patients of the 2nd group
      got rid of ticks for 20 days. The probable tick's reinforcement in children of
      the 3rd group did not change pathological muscle activity. The central mechanisms
      of cortical plasticity in behavioral therapy of ticks are discussed.

PMID- 14571677
TI  - [Epidemiology of epilepsy in the Novosibirsk region].

PMID- 14571678
TI  - [Modern forms of psychiatric care].

PMID- 14571679
TI  - [Use of lamictal monotherapy in epilepsy].

PMID- 14571680
TI  - [The use of pronoran (piribedil) in Parkinson's disease].

PMID- 14571681
TI  - [Sleep and epilepsy].

PMID- 14571682
TI  - [Preclinical epileptogenesis (compensation and prognosis)].

PMID- 14571683
TI  - Revised HIV prevention strategy: new hope or smoke screen?

PMID- 14571684
TI  - From neglect to care: a theory to guide HIV-positive incarcerated women in self
      care.
AB  - Self-care was investigated in this grounded theory study of 22 HIV-positive women
      incarcerated in a medium security prison in the southeastern United States.
      Findings revealed four phases in a social-psychological process of movement from
      neglect of health to self-care. Phases I and II revealed five social
      psychological cofactors that constrained self-care and promoted vulnerability to
      poor physical and emotional health over time. Phase I, "Recurring Memories of
      Abuse," focused on the damage of abuse histories; Phase II, "Repeating Harmful
      Coping Behaviors," described maladaptive coping behaviors that put women at risk
      for HIV infection and incarceration; Phase III, "Searching for Self-Care,"
      exposed the shock of incarceration and the HIV-positive diagnosis and symbolized
      a turning point in thinking about health and self-care. During Phase III, women
      discovered the possibility for better health through self-care. In Phase IV,
      "Connecting in Caring Relationships," women described their need for
      relationships that would help them promote and sustain self-care.

PMID- 14571685
TI  - Stigma and HIV: does the social response affect the natural course of the
      epidemic?
AB  - This article will review the theory of stigma and discuss its historical
      background. It will examine social responses to previously stigmatized veneral
      diseases and compare these responses with social responses to HIV. An analysis
      will be done using McGrath's (1992) theoretical measures to determine the affects
      of the social response of stigma on the infectious disease of HIV.

PMID- 14571686
TI  - Integrating health care for women diagnosed with HIV infection, substance abuse,
      and mental illness in Detroit, Michigan.
AB  - This article describes the evolution of Personalized Nursing, a comprehensive
      nursing practice model of care. Findings from several nursing research studies
      contributed to the development of Personalized Nursing. The model includes a
      practice model of the art of nursing care based on nursing theory and a specific
      nursing process that directs nursing care delivery. The process of care delivery
      includes location of hard-to-reach clients; linkage to health care providers;
      integration of care among providers for clients diagnosed with HIV, mental
      illness, and substance abuse; and strategies to promote retention in health care.
      Use of Personalized Nursing is designed to assist clients to improve their well
      being and increase positive health-related behaviors. Personalized Nursing has
      been used in urban landscapes to serve multiply diagnosed clients at risk for HIV
      infection. The model is currently being used in a study targeting multiply
      diagnosed women who are lost to follow-up from medical care.

PMID- 14571688
TI  - Not yet ready for prime time? Safe injection facilities in the overall prevention
      scheme.

PMID- 14571687
TI  - Participation in physical activity by persons living with HIV disease.
AB  - Physical activity (PA) may offer substantial health benefits for persons with HIV
      disease. The purpose of this study is to describe and explore physical activity
      behaviors in a sample of persons living with HIV disease. This descriptive
      correlational study surveyed 78 persons (n = 70 men; n = 8 women) from two
      outpatient settings. Results showed somewhat fewer of the participants met
      Healthy People 2010 PA recommendations than persons in the general population.
      Walking was the preferred PA. Average functional social support was significantly
      correlated with (a) weekly frequency of performing moderate 30-minute PA (r =
      .38, p < .01) and (b) HIV-RNA (viral load) values (r = -.37, p < .05).
      Significant correlations were also found between scores on general health status
      self-reported CD4+ cell counts (.33, p < .05) and HIV-RNA (.39, p < .05) values.
      Total friend functional social support was significantly (.32, p < .01)
      correlated with weekly frequency of moderate or vigorous PA.

PMID- 14571689
TI  - Reflections on faith and healing.

PMID- 14571690
TI  - Evaluation of mixture modeling with count data using NONMEM.
AB  - Mixture modeling within the context of pharmacokinetic (PK)/pharmacodynamic (PD)
      mixed effects modeling is a useful tool to explore a population for the presence
      of two or more subpopulations, not explained by evaluated covariates. At present,
      statistical tests for the existence of mixed populations have not been developed.
      Therefore, a simulation study was undertaken to evaluate mixture modeling with
      NONMEM and explore the following questions. First, what is the probability of
      concluding that a mixed population exists when there truly is not a mixture
      (false positive significance level)? Second, what is the probability of
      concluding that a mixed population (two subpopulations) exists when there is
      truly a mixed population (power), and how well can the mixture be estimated, both
      in terms of the population parameters and the individual subjects classification.
      Seizure count data were simulated using a Poisson distribution such that each
      subject's count could decrease from its baseline value, as a function of dose via
      an Emax model. The dosing design for the simulation was based on a trial with the
      investigational anti-epileptic drug pregabalin. Four hundred and forty seven
      subjects received pregabalin as add on therapy for partial seizures, each with a
      baseline seizure count and up to three subsequent seizure counts. For the
      mixtures, the two subpopulations were simulated to differ in their Emax values
      and relative proportions. One subpopulation always had its Emax set to unity
      (Emax hi), allowing the count to approach zero with increasing dose. The other
      subpopulation was allowed to vary in its Emax value (Emax lo = 0.75, 0.5, 0.25,
      and 0) and in its relative proportion (pr) of the population (pr = 0.05, 0.10,
      0.25, and 0.50) giving a total of 4.4 = 16 different mixtures explored. Three
      hundred data sets were simulated for each scenario and estimations performed
      using NONMEM. Metrics used information about the parameter estimates, their
      standard errors (SE), the difference between minimum objective function (MOF)
      values for mixture and non-mixture models (MOF (delta)), the proportion of
      subjects classified correctly, and the estimated conditional probabilities of a
      subject being simulated as having Emax lo (Emax hi) given that they were
      estimated as having Emax lo (Emax hi) and being estimated as having Emax lo (Emax
      hi) given that they were simulated as having Emax lo (Emax hi). The false
      positive significance level was approximately 0.04 (using all 300 runs) or 0.078
      (using only those runs with a successful covariance step), when there was no
      mixture. When simulating mixed data and for those characterizations with
      successful estimation and covariance steps, the median (range) percentage of 95%
      confidence intervals containing the true values for the parameters defining the
      mixture were 94% (89-96%), 89.5% (58-96%), and 95% (92-97%) for pr, Emax lo, and
      Emax hi, respectively. The median value of the estimated parameters pr, Emax lo
      (excluding the case when Emax lo was simulated to equal 0) and Emax hi within a
      scenario were within +/- 28% of the true values. The median proportion of
      subjects classified correctly ranged from 0.59 to 0.96. In conclusion, when no
      mixture was present the false positive probability was less than 0.078 and when
      mixtures were present they were characterized with varying degrees of success,
      depending on the nature of the mixture. When the difference between
      subpopulations was greater (as Emax lo approached zero or pr approached 0.5) the
      mixtures became easier to characterize.

PMID- 14571693
TI  - The rebalancing act.

PMID- 14571692
TI  - Pharmacokinetic and pharmacodynamic properties of insulin aspart and human
      insulin.
AB  - The preferred approach to determine the pharmacokinetic (PK) and pharmacodynamic
      (PD) properties of insulin analogues is the euglycemic glucose clamp. Currently
      non-compartmental data analytical approaches are used to analyze data. The
      purpose of the present study is to propose a novel compartmental-model for
      analysis of data from glucose clamp studies. Data used in this trial only
      involved 18 of the 20 originally treated subjects. Data was obtained from a
      crossover trial where 18 healthy subjects each received a single subcutaneous
      (s.c.) dose of 1.2 nmol/kg (body weight) insulin aspart (IAsp) or 1.2 nmol/kg
      human insulin (HI) during a euglycemic glucose clamp after overnight fast. Serum
      insulin and glucose concentrations were measured and the glucose infusion rate
      (GIR) was adjusted after dosing, to maintain blood glucose near basal levels.
      Individual model parameters were estimated for IAsp, HI, and the corresponding
      glucose and GIR data. We found statistically significant differences between most
      of the HI and IAsp pharmacokinetic parameters, including the sigmoidicity of the
      time course of absorption (1.5 for HI vs. 2.1 for IAsp (unit less), P = 0.0005,
      Wilcoxon Signed-rank test), elimination rate constant (0.010 min-1 for HI vs.
      0.016 min-1 for IAsp (P = 0.002)). The PD model parameters were mostly not
      different, except for the rate of insulin action (0.012 min-1 for HI vs. 0.017
      min-1 for IAsp (P = 0.03)). The model may provide a framework to account for
      different PK properties when estimating the PD properties of insulin and insulin
      analogues in glucose clamp experiments.

PMID- 14571691
TI  - Physiologically-based pharmacokinetics and molecular pharmacodynamics of 17
      (allylamino)-17-demethoxygeldanamycin and its active metabolite in tumor-bearing
      mice.
AB  - A whole-body physiologically-based model was developed to describe the
      pharmacokinetics of the ansamycin benzoquinone antibiotic 17-(allylamino)-17
      demethoxygeldanamycin (17AAG) and its active metabolite 17-(amino-)-17
      demethoxygeldanamycin (17AG) in blood, normal organs (lung, brain, heart, spleen,
      liver, kidney, skeletal muscle) and implanted human tumor xenograft in nude mice.
      The distribution of 17 AAG in all organs was described by diffusion-limited
      exchange models, while that of 17 AG was described by perfusion-limited models.
      The intrinsic clearances of 17AAG and 17AG in the liver were uniquely identified
      using local models and were estimated to be 4.93 ml/hr and 3.34 ml/hr. It was
      also estimated that the formation of 17AG in liver accounted for 40% of the 17AAG
      intrinsic clearance. The model for the distribution of both 17AAG and 17AG in the
      human breast cancer tumor xenograft included vascular, interstitial and
      intracellular compartments, which yielded the predicted cellular concentrations
      of 17AAG and 17AG two to three times higher than the corresponding whole tissue
      measurements at steady state. Estimates of the vascular-interstitial permeability
      surface-area product were similar for 17AAG and 17AG (0.23 ml/hr and 0.26 ml/hr).
      However, the interstitial to cellular transport rate of 17AG was three-fold
      greater than that of 17AAG, which resulted in the preferential uptake of 17AG
      over 17AAG in tumor. Indirect response models were developed to describe the
      combined action of 17AAG and 17AG on the onco-proteins Raf-1 and p185erbB2 in
      tumor. The half-life of endogenous protein turnover was estimated to be 22.6 hr
      for Raf-1 and 8.6 hr for p185erbB2, and both were comparable to corresponding
      values measured in vitro. A model for the molecular chaperon heat shock proteins
      HSP70 and HSP90 was developed based on the molecular mechanism of heat shock auto
      regulation and the action of 17AAG and 17AG on these proteins. The model provided
      in vivo estimates of endogenous HSP70 and HSP90 turnover. In modeling
      pharmacokmetics and pharmacodynamics, Bayesian inference was employed to estimate
      the kinetic, physiological and molecular parameters when prior information was
      available.

PMID- 14571694
TI  - The brain an owner's manual.

PMID- 14571695
TI  - How to heal a hypochondriac.

PMID- 14571696
TI  - Inside the foodlabs. A tantalizing tour of the secretive kitchens where culinary
      scientists fine-tune the flavors, architecture and, yes, "mouth feel" of
      tomorrow's hit foods.

PMID- 14571697
TI  - Postoperative changes on pulmonary function after laparoscopic and open
      cholecystectomy.
AB  - BACKGROUND/AIMS: We examined 28 patients who underwent cholecystectomy for acute
      or chronic cholecystitis and/or cholelithiasis in order to evaluate the effect of
      surgical technique on respiratory functional parameters. METHODOLOGY: We compared
      lung volume, flow parameters and blood gas indices in two groups of patients,
      eighteen of which underwent laparoscopic and ten of which open cholecystectomy,
      specifically on the 2nd and 8th postoperative day lung function indices were
      compared to preoperative values. The same anesthetic protocol was administered
      for all patients. No underlying illness other than the cholecystitis and/or
      cholelithiasis was present. RESULTS: From the results of lung volume parameters,
      ERV (%pred) data indicate a better expiratory ability for the Open
      Cholecystectomy [preop.: 93.10 (38.80), 8th day: 116.90 (63.69) compared to the
      Laparoscopic Cholecystectomy group (preop.: 105.39 (31.51), 8th day: 98.72
      (35.80). For IC (%pred.) parameter, in the Open Cholecystectomy group a marked
      but not statistically significant decrease remained into the 8th day (preop.:
      86.70 (16.40). 8th day: 68.40 (16.98)] whereas for the Laparoscopic
      Cholecystectomy group, IC %pred value reflected a better respiratory performance
      [preop.: 92.83 (17.87), 8th day: 82.50 (18.82)]. For RV and RV/TLC parameter
      measurements a marked increase in the %pred value was observed for the
      Laparoscopic Cholecystectomy group on the 8th postoperative day as compared to
      preoperative data [RV: 122.94 (42.80), 109.22 (33.23) respectively, RV/TLC:
      122.68 (31.10), 109.14 (21.56) respectively]. From the analysis of the flow
      parameters, a distinct difference was evident for PEF between the preoperative
      and 8th postoperative day data with the Laparoscopic Cholecystectomy group
      showing statistically significant better flow rates [preop.: 93.72 (15.91), 8th
      day: 84.33 (20.67)] as compared to the Open Cholecystectomy group [preop.: 82.30
      (22.98), 8th day: 59.10 (15.23)]. CONCLUSIONS: Having compared the 8th
      postoperative day with preoperative data for the two surgical methods, open
      cholecystectomy presented a better expiratory performance as compared to the
      laparoscopic method. However, laparoscopic cholecystectomy resulted in an overall
      better postoperative respiratory function.

PMID- 14571698
TI  - Radiosurgery for recurring liver metastases after hepatectomy.
AB  - BACKGROUND/AIMS: Most resected liver metastases from colorectal cancer recur. A
      minority of liver recurrences have been re-resected, but most re-resections fail
      and they decrease the postoperative performance status for a longer time than the
      initial resections, so that less demanding potentially curative treatments need
      evaluation. METHODOLOGY: Four out of 5 liver-only recurrences after 18
      consecutive liver resections were limited and suitable for radiosurgery. The
      patients were fixed in a frame and stereotactic irradiation with 20 Gy twice or
      15 Gy three times was delivered to the tumors. RESULTS: Limited side effects were
      seen, without medical need for hospital admission. Thirteen--101 months later,
      all treated tumors were locally controlled with complete radiologic remission of
      two of them. Only one patient recurred in the liver, with bilobar lesions
      preceded by extrahepatic spread. Neither recurrence would have been prevented by
      a rehepatectomy instead of irradiation. One patient died later tumor-free from
      stroke, two died from generalized tumors, and one remains in remission 101 months
      after radiosurgery. CONCLUSIONS: Radiosurgery of liver tumors merits further
      study, and may offer a less demanding alternative to resection for selected liver
      tumors with the prospect of long-term survival.

PMID- 14571699
TI  - Expression of receptor for advanced glycation end products (RAGE) in human
      biliary cancer cells.
AB  - BACKGROUND/AIMS: Amphoterin is considered as a regulator for the ability of
      invasion and migration in tumor cells and embryonic neurons through binding to
      RAGE (receptor for advanced glycation end products), a mult-iligand cell surface
      molecule of the immunoglobulin superfamily. METHODOLOGY: To see the involvement
      of RAGE in biliary cancer, three representative human biliary cancer cells (SK
      ChA-1, TGBC-1 and NOZC-1) were rendered for the study. Cell invasion ability was
      determined using Matrigel invasion assay. The expression of RAGE protein was
      studied by Western blotting. RESULTS: Cell invasion assay through Matrigel showed
      high invasion potential in SK-ChA-1 and NOZC-1 (40.3 +/- 3.27, 48.7 +/- 4.8); low
      invasion potential in TGBC-1 (25.7 +/- 2.8). RAGE was strongly expressed in SK
      ChA-1 and NOZC-1 that have high invasion ability. On the contrary, RAGE was
      faintly expressed in TGBC-1 that has low ability. CONCLUSIONS: RAGE is expressed
      in concordance to the invasion ability of the human biliary cancer cells. Control
      of this molecule could be a key to regulate the invasion ability of biliary
      cancers.

PMID- 14571700
TI  - The clinical utility of string-PCR test in diagnosing Helicobacter pylori
      infection.
AB  - BACKGROUND/AIMS: Non-invasive string test has been reported as being convenient
      and capable of yielding bacteria by means of gastric juice sampling in the
      diagnosis of Helicobacter pylori infection. Molecular methods, such as polymerase
      chain reaction for the amplification of DNA, are desirable for the detection of
      minute quantities of H. pylori. We planned to evaluate the diagnostic efficiency
      of the combination of the string test and polymerase chain reaction and determine
      whether the string polymerase chain reaction test could obtain more information
      in conditions where the bacterial load is so low that other diagnostic tests fail
      to confirm the presence of H. pylori. METHODOLOGY: We enrolled 48 dyspeptic
      patients, including 29 males and 19 females, with a mean age of 52.5 years. Each
      patient received endoscopy and biopsy-based tests, including RUT (rapid urease
      test), cultures, and histology, followed by 13C-UBT (13Carbon urea breath test).
      We used the string test, (Entero-Test H. pylori, HDC Corporation, CA, US), for
      gastric juice sampling. The specimen was further analyzed by polymerase chain
      reaction for the presence of H. pylori with the primer for cagA gene, which is
      highly prevalent in Taiwan. H. pylori infection was considered as positive when
      either culture yield was positive, or when two of the other three tests,
      including RUT, histology, and 13C-UBT, were positive. RESULTS: Of the total 48
      patients, 34 patients were H. pylori-positive, and 14 were H. pylori-negative. A
      fragment of 349 bp of polymerase chain reaction products was detected by agarose
      gel electrophoresis in 32 out of 34 patients who was classified as H. pylori
      positive. The sensitivity, specificity, positive predictive value, and negative
      predictive value of the string polymerase chain reaction test were 94.12%,
      96.97%, 92.86%, and 86.67%, respectively. These results are comparable to 13C-UBT
      and RUT, and better than histology and culture. One subject, who tested as H.
      pylori-negative according to the diagnostic criteria, had positive 13C-UBT and
      string polymerase chain reaction test results. Further sequencing of the DNA
      obtained from the results of polymerase chain reaction product was performed and
      it showed 98% identities with the known sequence of cagA strain H. pylori
      (GenBank accession number: AF249275). CONCLUSIONS: The string polymerase chain
      reaction test is non-invasive and provides direct bacterial yields. Its
      diagnostic efficiency is comparable with 13C-UBT and RUT in detecting H. pylori
      infection. Also, with the assistance of polymerase chain reaction and DNA
      sequencing, we can diagnose H. pylori infection even when the bacterial load is
      low. Further application of string polymerase chain reaction test in the genetic
      analysis of virulent and resistant strains seems promising.

PMID- 14571702
TI  - A case of hepatic artery embolization and partial arterialization of the portal
      vein for intraperitoneal, hemorrhage after a pancreaticoduodenectomy.
AB  - We report a case of hepatic artery embolization and partial portal vein
      arterialization for the treatment of a delayed massive hemorrhage after a
      pancreaticoduodenectomy. A 70-year-old male underwent a pancreaticoduodenectomy
      for the treatment of lower bile duct cancer. A slight discharge of pancreatic
      juice was recognized early during the postoperative period. A delayed massive
      hemorrhage occurred on postoperative day 34, resulting in hypotensive shock.
      Angiography and computed tomography examinations revealed bleeding from a
      pseudoaneurysm at the stump of the gastroduodenal artery and portal vein
      compression by the hematoma. Embolization of the stump of the gastroduodenal
      artery resulted in the total occlusion of the hepatic artery. We performed a
      partial portal vein arterialization via side-to-side anastomosis of a branch of
      the ileal artery and vein. The partial portal oxygen pressure increased from 70
      mmHg to 90 mmHg. A liver abscess was recognized two weeks after the
      arterialization, but was successfully treated by percutaneous transhepatic
      drainage. The patient was discharged from hospital in good condition on
      postoperative day 69. Whether the partial portal vein arterialization was
      effective is unclear, but partial portal vein arterialization should be
      considered as an option in cases of total hepatic artery occlusion with
      impairment of portal blood flow.

PMID- 14571701
TI  - Regression of hepatocellular cancer in a patient treated with arginine deiminase.
AB  - We report the first pharmacokinetic and clinical response data from a patient
      with unresectable hepatocellular cancer treated with a new drug, ADI PEG20,000 mw
      (arginine deiminase-polyethylene glycol 20,000 molecular weight). A single
      patient with idiopathic cirrhosis and unresectable hepatocellular cancer was
      treated with escalating dosages of ADI-PEG20,000 mw. Human hepatocellular cancer
      has been found to be arginine-dependent for growth because of loss of expression
      or arginosuccinate synthetase, the rate-limiting enzyme in the conversion of
      citrulline to arginine. Thus, an arginine-degrading enzyme like ADI-PEG20,000 mw
      should produce cell death in hepatocellular cancer cells without significantly
      affecting normal cells. There was a dose-dependent reduction of plasma arginine
      levels after weekly intramuscular administration of ADI-PEG20,000 mw. Successive
      treatment cycles at the optimal biologic dose of 160 IU/m2 led to reduction in
      tumor size and serum alpha-fetoprotein levels. Sufficient tumor cytoreduction was
      achieved with ADI-PEG20,000 mw treatment to permit surgical treatment. The
      patient developed no toxicities or side effects related to ADI-PEG20,000 mw
      treatment. The results in a single patient with unresectable hepatocellular
      cancer treated with ADI-PEG20,000 mw suggests this may be a promising, low
      toxicity treatment. Full-scale clinical trials have been initiated.

PMID- 14571703
TI  - Living related heterotopic auxiliary partial liver transplantation for extremely
      small-for-size graft in fulminant liver failure.
AB  - Adult living related liver transplantation seeks a balance between donor safety
      and the need to save the recipient's life. A small-for-size graft is a major
      obstacle for high-risk patients. We experienced a case of heterotopic auxiliary
      partial liver transplantation with extremely small-for-size graft for fulminant
      liver failure. The other reasons why we chose to perform heterotopic auxiliary
      partial liver transplantation were acute renal failure, subshock state, and a
      left lobe volume of 24% in the standard liver volume of the donor. Hepatic vein
      reconstruction was made using an inferior meserteric vein patch graft. Portal
      vein reconstruction was made using end-to-side anastomosis employing an
      interposed left external iliac vein. The left hepatic artery of the graft was
      connected to the distal gastroduodenal artery. The patient was discharged 3
      months after transplantation. We would recommend heterotopic auxiliary partial
      liver transplantation as an optional procedure for patients with severe
      preoperative conditions or extremely small-for-size graft donors.

PMID- 14571704
TI  - Alternative treatment for gallbladder stones in portal venous thrombosis.
AB  - BACKGROUND/AIMS: Cholecystectomy for treatment of gallbladder stones in patients
      with portal vein thrombosis can be a hazardous procedure. Dissection into an area
      of thin-walled collateral vessels can trigger troublesome bleeding and consequent
      blood coagulation disorders. METHODOLOGY: In order to avoid dissection,
      cholecysto-jejunostomy was used as the treatment of choice in three patients with
      symptomatic gallbladder stones and portal vein thrombosis. RESULTS: Surgical
      procedure was uneventful, blood or plasma transfusions were not required either
      at surgery or afterwards. Pre- and postoperative hematocrit evaluations showed no
      difference, as well as liver function tests. The procedure was well tolerated and
      patients were discharged from day 5 to 7. Follow-up ranged from 2 to 3 years, no
      biliary complications were found during this period. CONCLUSIONS: Choleysto
      jejunostomy is a safe procedure and can be used as an effective treatment of
      symptomatic gallbladder stones in patients with portal vein thrombosis.

PMID- 14571705
TI  - Endoscopic sphincterotomy in 100 patients scheduled for laparoscopic
      cholecystectomy: ultrasound evaluation.
AB  - BACKGROUND/AIMS: The aim of the study was to determine to what extent
      ultrasonography may monitor the process of sphincterotomy and its effectiveness.
      The study also aimed at determining the sensitivity and specificity of
      ultrasonography in detecting choledocholithiasis, in comparison with the results
      of endoscopic retrograde cholangiopancreatography. METHODOLOGY: Between January
      1995 and June 2001, endoscopic sphincterotomy was performed on 100 patients with
      suspected synchronous choledocholithiasis in preparation for laparoscopic
      cholecystectomy. The main parameters evaluated in the ultrasonography image
      included the breadth of the common bile duct and absence or presence of
      concrements in bile ducts before and after sphincterotomy. RESULTS: Applied
      before the endoscopic operation, ultrasonography revealed choledocholithiasis in
      58 patients and dilatation of the common bile duct in 95 patients. Endoscopic
      retrograde cholangiopancreatography confirmed choledocholithiasis in 74 patients,
      after sphincterotomy concrements were removed in 63 persons. In 26 patients
      sphincterotomy was performed for stenosis of Vater's papilla. Patients with the
      breadth of the duct > 10 mm, were referred to a check-up examination.
      CONCLUSIONS: Compared with endoscopic retrograde cholangiopancreatography,
      ultrasonography correctly specifies the breadth of the bile duct and properly
      monitors the process of endoscopic sphincterotomy, but is less accurate in
      determining the occurrence of choledocholithiasis, and sensitivity in the test
      amounted to 73%, and specificity of the examination--84.5%.

PMID- 14571706
TI  - Long-term follow-up after endoscopic biliary stent placement for bile duct
      strictures from laparoscopic cholecystectomy.
AB  - BACKGROUND/AIMS: The outcome of endoscopic biliary stent insertion for
      postoperative bile duct stenosis was retrospectively evaluated. METHODOLOGY:
      Fifty-seven patients with biliary stenosis from laparoscopic cholecystectomy were
      included from February 1992 to January 2000. One to three stents were inserted
      for an average of 12.4 months, with stent exchange every 3 months to avoid
      cholangitis caused by clogging. RESULTS: Successful stent insertion was achieved
      in 43/57 (75.4%) patients. Stent insertion failed in 10 patients with complete
      and in 4 patients with incomplete biliary obstruction. Early complications
      occurred in 4 patients. Late complications occurred in 5/43 patients. Five
      patients experienced recurrence of stenosis. CONCLUSIONS: Endoscopic treatment
      should be the initial management of choice for postoperative bile duct stenosis.

PMID- 14571707
TI  - Gallbladder motility in healthy volunteers: effects of age, gender, body mass
      index, and hair color.
AB  - BACKGROUND/AIMS: Ultrasonographic determination of gallbladder motility is
      sparsely performed in clinical practice as the examination is considered to be
      time consuming and there is uncertainty about a number of parameters possibly
      influencing the results. The aims of this study were a) to establish normal
      values for a simple ultrasonographic test and b) to evaluate the influence of
      different parameters on gallbladder motility. METHODOLOGY: In 62 systematically
      age- and sex-matched healthy volunteers, ultrasonographic measurements of
      gallbladder volume (ellipsoid method, planimetry and sum-of-cylinders method)
      were performed fasting and 5, 10, 20, 30, 40, 50, 60, 70 and up to 75 min after
      stimulation with a standardized high-caloric liquid meal. RESULTS: Using the
      ellipsoid method, gallbladder fasting volume (V0) reached a mean value (+/- SD)
      of 24.6 +/- 10.0 mL with an ejection fraction of 65.9 +/- 19.1%. Age, gender and
      hair color did not influence parameters of gallbladder contraction. Body mass
      index showed a weak correlation with V0 but not with ejection fraction. There was
      a highly significant correlation between the ellipsoid method and longitudinal
      planimetry and the sum-of-cylinders method, respectively. CONCLUSIONS:
      Ultrasonographic measurement of gallbladder motility in healthy volunteers shows
      a very wide scattering of normal values. In the interpretation of gallbladder
      emptying, age, gender and body mass index do not have to be considered.
      Determination of gallbladder motility may be performed by a rather simple
      approach with oral stimulation and ellipsoid method or longitudinal planimetry as
      easily applicable ultrasonographic measurements.

PMID- 14571708
TI  - Magnetic resonance cholangiopancreatography in patients with upper abdominal
      pain: a prospective study.
AB  - BACKGROUND/AIMS: To determine the role of magnetic resonance
      cholangiopancreatogram with conventional abdominal magnetic resonance examination
      in patients presenting clinically with upper abdominal pain and abnormal liver
      function tests and to compare the findings with endoscopic retrograde
      cholangiopancreatogram results. METHODOLOGY: Magnetic resonance
      cholangiopancreatogram and endoscopic retrograde cholangiopancreatogram were done
      in 77 patients. Conventional magnetic resonance examination of the liver and
      upper abdomen was done first followed by magnetic resonance
      cholangiopancreatogram using a half fourrier single shot turbo spin echo
      sequence. Conventional endoscopic retrograde cholangiopancreatogram was done by
      direct intraductal injection of radiographic contrast material through a
      duodenoscope under fluoroscopy control. RESULTS: Endoscopic retrograde
      cholangiopancreatogram failed in 7 patients (9%) and Magnetic resonance
      cholangiopancreatogram images were inadequate in 3 patients (4%). The findings of
      adequate magnetic resonance exams in 74 patients were: choledocholithiasis in 24
      patients (32%), bile duct stricture in 19 patients (26%), normal biliary ducts in
      29 patients (39%) and dilated biliary ducts with no definite cause in 2 patients
      (3%). The findings of successful endoscopic retrograde cholangiopancreatograms in
      67 patients after exclusion of inadequate magnetic resonance
      cholangiopancreatograms were: choledocholithiasis in 25 patients (37%), bile duct
      stricture in 18 patients (27%), normal biliary ducts in 21 patients (31%) and
      dilated biliary ducts with no evident cause in 2 patients (3%) and hemobilia in 1
      patient (2%). CONCLUSIONS: Magnetic resonance cholangiopancreatogram is a non
      invasive technique, its accuracy is increased if it is combined with conventional
      abdominal magnetic resonance exam and it can replace the endoscopic retrograde
      cholangiopancreatogram.

PMID- 14571710
TI  - Diagnostic dilemmas in biliary strictures mimicking cholangiocarcinoma.
AB  - BACKGROUND/AIMS: Bile duct strictures may be malignant or benign. In the absence
      of previous biliary surgery a precise preoperative diagnosis is often difficult,
      in particular when a tumor mass is absent in the preoperative radiologic
      findings. METHODOLOGY: A review of 179 patients observed between 1982 and 2001 by
      the same surgical team with a preoperative diagnosis of malignant stricture of
      the biliary tree. A surgical procedure was performed in 153 of these cases.
      RESULTS: The presence of a malignant stricture was confirmed by final pathologic
      examination in 32 of 38 cases (96%) in which a curative resection was performed.
      A final diagnosis of inflammatory stricture secondary to choledocholithiasis was
      made in 3 of the remaining 6 cases (4%), along with one case each of sclerosing
      cholangitis, granular cell tumor and Mirizzi's syndrome, respectively.
      CONCLUSIONS: Precise preoperative evaluation of biliary structures can be very
      difficult when a tumor mass is absent. Despite the use of invasive procedures and
      new techniques such as magnetic resonance cholangiopancreatography, a false
      positive rate of 4% may be expected. However, whenever a malignancy is not
      definitely excluded, biliary strictures should be treated as a
      cholangiocarcinoma.

PMID- 14571709
TI  - Sphincterotomy in patients with gallstones, elevated LFTs and a normal CBD on
      ERCP.
AB  - BACKGROUND/AIMS: To determine whether an endoscopic sphincterotomy affects
      outcome in patients with symptomatic gallstones, elevated liver function tests
      and a normal common bile duct on endoscopic retrograde cholangiopancreatogram.
      METHODOLOGY: A total of 163 patients with symptomatic gallstones and elevated
      liver function tests, and found to have a normal common bile duct on endoscopic
      retrograde cholangiopancreatogram were included in the study. Endoscopic
      sphincterotomy was performed in 78 (47.8%) patients, while 85 (52.1%) patients
      did not have an endoscopic sphincterotomy. The two groups were compared for
      detection of small unseen common bile duct stones/debris, endoscopic retrograde
      cholangiopancreatogram related complications, and biliary complications after
      cholecystectomy. RESULTS: Small common bile duct stones/debris were recovered in
      11/43 (25.5%) patients who had instrumentation of the common bile duct performed
      after endoscopic sphincterotomy. Common bile duct instrumentation was not
      performed in any of the patients without endoscopic sphincterotomy. No patient
      had any biliary complication after cholecystectomy, both in the immediate
      postoperative period and on a follow-up of 37.5 +/- 13.6 months (range 17-66).
      Endoscopic retrograde cholangiopancreatogram related complications occurred in 8
      patients who had an endoscopic sphincterotomy and in 2 without endoscopic
      sphincterotomy (p < 0.05). CONCLUSIONS: Performing an endoscopic sphincterotomy
      in these patients increases the detection of small unseen common bile duct
      stones/debris without changing the clinical outcome after cholecystectomy. It
      also increases the endoscopic retrograde cholangiopancreatogram related
      complication rate, and therefore may not be necessary.

PMID- 14571711
TI  - Mucin-producing carcinoma of the cystic duct that caused obstructive jaundice.
AB  - We report a very rare case of what appeared to be mucin-producing carcinoma of
      the cystic duct, and this is the forth case recorded in the English-language and
      Japanese literature. The patient was a 67-year-old man with a chief complaint of
      dark urine and jaundice. Cholangiography via an endoscopic nasobiliary drain
      showed dilatation of the common hepatic duct to 14 mm, with no visualization of
      the cystic duct or gallbladder, and an approximately 15-mm filling defect was
      observed at the junction of the common bile duct and the cystic duct. Based on
      these findings a diagnosis of cancer of the middle portion of the bile duct was
      made. Cholecystectomy and resection of the bile duct with dissection of regional
      lymph Nodes and choledochoduodenostomy were performed. About a 1-cm mass was
      palpable in the region of the cystic duct, and the gallbladder contained mucin
      some of which reached the common bile duct. Histological examination revealed
      well-differentiated ductal adenocarcinoma infiltrating the serosa, in which mucus
      production was observed. The patient was discharged on postoperative day 50. At
      the present time, 38 months postoperatively, there are no signs of recurrence,
      and he is attending the outpatient clinical in good health.

PMID- 14571712
TI  - Xanthogranulomatous cholecystitis mimicking stage IV gallbladder cancer.
AB  - Patients with xanthogranulomatous cholecystitis often undergo excessive surgical
      resections because of difficulty in distinguishing their condition from
      gallbladder cancer. Herein we present a patient with xanthogranulomatous
      cholecystitis mimicking stage IVA gallbladder cancer who underwent a
      hepatopancreatoduodenectomy. The 64-year-old man was admitted to the local
      hospital with a chief complaint of high fever, hypochondrolgia and jaundice. One
      month later, he transferred to Tsukuba University Hospital with a hard palpable
      fixed large tumor in the right hypochondrium. Computed tomography and
      ultrasonography showed a tumor originating from the gallbladder extending to the
      adjacent liver parenchyma, as well as nodes in the hepatoduodenal ligaments
      approaching the head of the pancreas. Endoscopic retrograde
      cholangiopancreatography failed to exhibit the gallbladder despite the
      visualization of irregular narrowing of the common hepatic duct. Angiography
      demonstrated encasement of the right hepatic artery and narrowing of the right
      portal vein. On the other hand, the level of serum carbohydrate antigen 19-9 was
      within normal range. Based on those findings, a right hepatic lobectomy with
      pancreaticoduodenectomy was conducted under the preoperative and intraoperative
      diagnosis of gallbladder cancer; stage IVA. The gross findings of the surgical
      specimen showed an ill-defined yellowish hard mass, but microscopic examination
      demonstrated xanthogranulomatous cholecystitis. The presented case shows that
      xanthogranulomatous cholecystitis can mimic an advanced gallbladder carcinoma
      when the severe chronic inflammatory changes have extended to the liver hilum
      down to the head of the pancreas. However, the normal level of tumor markers in
      all clinical courses might be a reason to consider xanthogranulomatous
      cholecystitis instead of gallbladder cancer. Even when the correct diagnosis is
      made, the possibility that the adjacent organs should be resected is not remote.

PMID- 14571713
TI  - Mirizzi syndrome with cholecysto-choledocal fistula with a high CA19-9 level
      mimicking biliary malignancies: a case report.
AB  - Mirizzi syndrome type II is a form of obstructive jaundice caused by a stone
      impacted in the gallbladder neck or the cystic duct that impinges on the common
      hepatic duct with a cholecysto-choledochal fistula. Preoperative recognition is
      necessary to prevent injury to the common duct during surgery. We present a
      patient with an operative diagnosis of type II Mirizzi syndrome, which was not
      originally indicated in the preoperative work-up; in particular endoscopic
      retrograde cholangiopancreatography showed stenosis of the middle third of the
      hepatic duct along with markedly elevated serum CA19-9 levels (up to 35,000
      U/mL). Surgical specimen examination did not reveal the presence of neoplasia. We
      performed cholecystectomy and a jejunal loop was brought up and anastomosed to
      the common duct at the hilar level in a Roux-en-Y fashion. In cases such as ours
      with extensive fibrosis and inflamed tissue mimicking cholangiocarcinoma or
      gallbladder carcinoma, a wide hepaticojejunostomy is required to establish
      adequate biliary drainage.

PMID- 14571714
TI  - Extrahepatic course of the subsegmental biliary branch of the anteroinferior area
      of the liver.
AB  - Two cases in whom the subsegmental biliary branch of the anterio-inferior area
      (B5) coursed to the right laterally and inferiorly, forming a caudally convex
      arc, and running near the neck of the gallbladder are reported. In these two
      patients, the B5 branches were not aberrant, however, these branches were running
      near the gallbladder bed extrahepatically, which alerted us to the risk of their
      inadvertent division. The relationship between the cystic duct and the B5 branch
      is clinically important during cholecystectomy, especially laparoscopic
      cholecystectomy.

PMID- 14571715
TI  - Hepatectomy for proximal bile duct carcinoma in a patient with situs inversus; a
      case report.
AB  - Situs inversus is a rare condition which mandates a full understanding of all
      anatomic relationships prior to invasive procedures. A 76-year-old woman with
      situs inversus presented with fever and rigors. She had previously undergone
      endoscopic sphincterotomy and lithotomy for choledocholithiasis, and laparoscopic
      cholecystectomy for cholecystolithiasis. Laboratory examination revealed
      hyperbilirubinemia and transaminasimia. Percutaneous transhepatic biliary
      drainage, percutaneous transhepatic cholangioscopy, percutaneous transhepatic
      portography, percutaneous transhepatic portal embolization, and visceral
      angiography were performed without complications. She underwent right hepatic
      lobectomy, caudate lobectomy and extrahepatic bile duct resection for papillary
      adenocarcinoma of the proximal bile duct. Full investigation of the anatomical
      relationships between the biliary tree and the vascular system in the hepatic
      hilus enabled safe hepatectomy in a patient with situs inversus.

PMID- 14571716
TI  - Plasma amino acid levels in patients with colorectal cancers and liver cirrhosis
      with hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: A variety of cancer-bearing patients have been shown to have
      disturbances in carbohydrate, lipid and protein metabolism. The complex of
      metabolic derangements of protein in cancer patients may be reflected by
      alteration in the plasma free amino acid profile. In this study, we try to
      investigate the plasma free amino acid profile in patients with colorectal cancer
      and liver cirrhosis with hepatocellular carcinoma, which are the most common
      cancers in Taiwan. METHODOLOGY: Fasting venous blood samples were drawn from
      sixteen control volunteers and 42 cancer-bearing patients including 14 early
      stage colorectal cancer patients (Duke A and B), 18 late stage ones (Duke C and
      D) and 10 liver cirrhotic patients with hepatocellular carcinoma. Seventeen amino
      acid levels were measured using a Beckman amino acid analyzer. RESULTS: About one
      third of early or late colorectal cancer patients had body weight loss more than
      10% in half a year and were defined as malnourished. For individual amino acids,
      in early colorectal cancer patients, the plasma level of most essential amino
      acids and non-essential amino acids decreased (significantly in Tyr, Ala, Met,
      Phe and Thr). In late stage colorectal cancer patients and patients with liver
      cirrhosis with hepatocellular carcinoma, plasma levels of most essential amino
      acids and non-essential amino acids decreased more obviously. For group amino
      acids, the plasma levels of essential amino acids, non-essential amino acids,
      gluconeogenic amino acids and branched-chain amino acids were also lower in the
      cancer patients than those in control volunteers. The difference was also
      noticeably significant in patients with late stage colorectal cancer and liver
      cirrhosis with hepatocellular carcinoma. The plasma free amino acid patterns in
      colorectal cancer patients are quite different from those in patients with non
      gastrointestinal cancer and weight loss. The plasma level of essential amino
      acids and branched-chain amino acids was not kept within normal range in
      colorectal cancer patients. Elevation of plasma aromatic amino acids and
      methionine levels usually observed in liver cirrhotic patients without
      hepatocellular carcinoma was not apparent in our cirrhotic patients with
      hepatocellular carcinoma. CONCLUSIONS: The plasma free amino acid patterns in our
      colorectal cancer patients and cirrhotic patients with hepatocellular carcinoma
      were rather characteristic. The results will offer useful tools for improving
      diagnosis and therapy.

PMID- 14571717
TI  - Immunohistochemical detection of Fas and apoptosis in type-1 autoimmune
      hepatitis.
AB  - BACKGROUND/AIMS: Although Fas expression has been reported in liver with chronic
      viral hepatitis and primary biliary cirrhosis, little is known about Fas
      expression and apoptosis in type-1 autoimmune hepatitis. The aim of this study
      was to investigate whether the expression of Fas and apoptosis are found in liver
      with autoimmune hepatitis. The relationship between Fas expression and
      clinicopathological findings including the occurrence of apoptosis was also
      investigated. METHODOLOGY: Fas expression and apoptosis were
      immunohistochemically examined in liver tissues from 20 patients with autoimmune
      hepatitis and five control subjects using specific antibodies against Fas and
      single-stranded DNA. The grade of expression of Fas and apoptosis was evaluated
      and compared with histological findings and the results of liver function tests
      in each patient. RESULTS: Fas expression in hepatocytes was detected in all
      patients with autoimmune hepatitis, while Fas expression was not detected in
      control livers. The Fas-positive hepatocytes were particularly abundant in those
      areas facing piecemeal and confluent necrosis. In 30% of autoimmune hepatitis
      cases, bile-duct cells were faintly stained for Fas. A few hepatocytes positive
      for single-stranded DNA were found in the areas facing piecemeal necrosis and
      confluent necrosis. In 95% cases, many bile-duct cells were positive for single
      stranded DNA. No relationship between the expression of Fas and single-stranded
      DNA was found in hepatocytes or bile-duct cells. However, the degree of Fas
      expression in hepatocytes significantly correlated with serum transaminase
      concentrations and was increased in parallel with the grade of activity but not
      with the stage of fibrosis. CONCLUSIONS: We have demonstrated that Fas expression
      is detected in hepatocytes of the liver with autoimmune hepatitis and that the
      level of Fas expression reflects the severity of inflammation in autoimmune
      hepatitis.

PMID- 14571718
TI  - PGP9.5 overexpression in esophageal squamous cell carcinoma.
AB  - BACKGROUND/AIMS: PGP9.5 is a ubiquitin hydrolase widely expressed in neuronal
      tissue at all stages of neuronal differentiation and has been used as a
      neuroendocrine marker. Recently, it has been proved that PGP9.5 expression was
      highly observed in squamous cell carcinoma of lung cancer, suggesting that it
      might be a tumor marker for squamous cell carcinoma. To better characterize its
      role in digestive tract cancers, we examined PGP9.5 expression retrospectively in
      esophageal cancers. METHODOLOGY: We examined PGP9.5 expression retrospectively in
      40 resected esophageal cancers (squamous cell carcinoma) and 10 gastric cancers
      (adenocarcinoma) using immunohistochemistry. RESULTS: Of 40 esophageal cancer
      specimens, 19 (48%) exhibited positive staining with PGP9.5 in most tumor cells,
      while no PGP9.5 expression was observed in any of the 10 gastric cancers.
      CONCLUSIONS: Although the precise mechanism underlying the effect of PGP9.5 on
      oncogenicity remains to be proven, it was confirmed that it may be a potential
      marker for esophageal squamous cell carcinoma.

PMID- 14571719
TI  - Prognostic significances of tumor-infiltrating S-100 positive dendritic cells and
      lymphocytes in patients with hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: To investigate the prognostic significances of dendritic cells
      and lymphocytes infiltration in hepatocellular carcinoma. METHODOLOGY: The
      clinicopathological and follow-up data of 44 patients with hepatocellular
      carcinoma, who underwent curative resection of tumor in our hospital from January
      1995 to July 1996, were collected. Immunohistochemical staining was employed to
      detect the S-100 positive dendritic cells in the tumor tissue, and lymphocytes
      infiltration was evaluated simultaneously. The relationship of the tumor
      infiltrating dendritic cells and lymphocytes to the postoperative recurrence-free
      time and survival rate was analyzed. RESULTS: Either the tumor-infiltrating
      dendritic cells or the tumor-infiltrating lymphocytes alone had no significant
      relationship to the postoperative recurrence-free time and survival rate. By
      taking into consideration both tumor-infiltrating dendritic cells and lymphocytes
      simultaneously, the patients were classified into two groups. Group A included
      patients having dendritic cell counts > or = 20 cells/10 high power fields
      together with positive lymphocytes infiltration (n = 17), and group B consisted
      of patients having dendritic cell count > or = 20 cells/10 high power fields but
      with negative lymphocytes infiltration or dendritic cell count < 20 cells/10 high
      power fields with either positive or negative lymphocytes infiltration (n = 27).
      There were no significant differences in clinicopathological features between two
      groups. The recurrence-free time was markedly longer in group A as compared with
      group B, with a median time of 21.6 months for group A and 4.1 months for group B
      (P < 0.05). The 1-, 3-, 4-year survival rates were significantly greater in group
      A than those in group B, being 83.5% vs. 42.2%, 61.8% vs. 28.4% and 48.7% vs.
      23.0%, respectively (P < 0.01). CONCLUSIONS: Marked infiltration of dendritic
      cells together with lymphocytes in tumor tissue was closely related to the
      improved clinical prognosis in patients with hepatocellular carcinoma, and
      represented as an independent prognostic factor.

PMID- 14571720
TI  - Differentiation of benign and malignant lymph nodes with contrast-enhanced
      echolymphography using endoscopic ultrasound-guided puncture.
AB  - BACKGROUND/AIMS: Although endoscopic ultrasonography is considered the most
      useful diagnostic modality for the regional staging, the capability of diagnosing
      lymph node metastasis based on endoscopic ultrasonography images alone is not
      sufficient. To improve the capability of differential diagnosis of lymph node
      enlargement, contrast-enhanced echolymphography was performed using endoscopic
      ultrasonography-guided puncture. METHODOLOGY: Contrast-enhanced echolymphography
      was performed in 8 metastatic lymph nodes surgically resected from patients with
      gastrointestinal cancers (in vitro study) and also in 55 patients in whom
      abdominal lymph node swelling was indicated by endoscopic ultrasonography (in
      vivo study). Lymph nodes were punctured under real-time endoscopic
      ultrasonography guidance, and carbon dioxide microbubbles were injected to
      evaluate echo features before and after microbubbles injection. RESULTS: Contrast
      enhanced echolymphography of freshly resected metastatic lymph nodes showed
      nonhomogeneous echo patterns. In regions demonstrating filling defects detected
      by contrast-enhanced echolymphography, neoplastic infiltration was pathologically
      observed. In almost all of the malignant lymph nodes studied in vivo, filling
      defects and heterogeneous enhancements were observed by contrast-enhanced
      echolymphography. However, contrast-enhanced echolymphography demonstrated
      uniform patterns in most of the benign group. The sensitivity, specificity,
      positive and negative predictive value, and accuracy of differential diagnosis by
      contrast-enhanced echolymphography were 95.8%, 90.3%, 88.5%, 96.6%, and 92.7%,
      respectively. CONCLUSIONS: Contrast-enhanced echolymphography is a useful method
      for help in the differentiation between reactive and malignant alterations of
      lymph nodes.

PMID- 14571721
TI  - p53 and p21WAF1/CIP1 in hepatitis B virus related hepatocarcinogenesis.
AB  - BACKGROUND/AIMS: This study was undertaken to determine the expression
      p21WAF1/CIP1 and p53, the main regulator of G1 restriction point, in hepatitis B
      virus related hepatocarcinogenesis and their role in regulation of cell dynamics.
      METHODOLOGY: Immunohistochemistry for p21WAF1/CIP1, p53 and Ki-67 and terminal
      deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling were
      preformed in 8 low grade dysplastic nodules, 7 high grade dysplastic nodules, 58
      hepatocellular carcinomas, and 62 chronic hepatitis/cirrhosis. In 33
      hepatocellular carcinomas with fresh frozen tissue, p21WAF1/CIP1 mRNA was studied
      by reverse transcriptase polymerase chain reaction. RESULTS: Immunostaining for
      p21WAF1/CIP1 and p53 was positive in 28% and 38% of hepatocellular carcinomas and
      higher in poorly differentiated hepatocellular carcinomas, whereas it was
      negative in all of chronic hepatitis/cirrhosis and dysplastic nodules. In
      hepatocellular carcinomas with p21WAF1/CIP1 mRNA amplified, 31% showed the
      protein expression indicating post-transcriptional regulation. The rate of
      apoptosis and proliferation showed significant correlation with p53 status,
      however not with p21WAF1/CIP1 in hepatocellular carcinomas. Induction of
      p21WAF1/CIP1 was regulated by both p53 dependent and independent pathway.
      CONCLUSIONS: In hepatitis B virus related hepatocarcinogenesis, p21WAF1/CIP1 and
      p53 are suggested to be involved in late stage of tumor progression rather than
      in early stage of dysplastic nodules and p53 is considered to be the main
      regulator of the cell dynamics.

PMID- 14571722
TI  - Therapeutic effect of oral recombinant human granulocyte macrophage-colony
      stimulating factor in radiotherapy-induced esophagitis.
AB  - BACKGROUND/AIMS: Radiation-induced esophagitis is one of the most important early
      side effects of irradiation of chest, and head and neck malignancies. This
      condition often leads to interruption of radiotherapy for several days. An
      effective treatment for reducing the incidence and severity of this complication
      has not yet been found. We aimed to investigate the therapeutic effect of rhGM
      CSF on radiation-induced esophagitis in the patients with chest or head and neck
      malignancies. METHODOLOGY: Ninety-seven patients with chest or head and neck
      malignancies who had not previously received radiation therapy, were treated with
      radiotherapy, concurrent or sequential chemoradiotherapy. Forty-eight patients
      who had grade 1, 2 or 3 esophagitis symptoms according to Radiation Therapy
      Oncology Group radiation morbidity score, underwent upper gastrointestinal
      endoscopy. In the patients with grade 3 esophagitis (according to Kuwahata's
      scoring system) rhGM-CSF was administered for 5-10 consecutive days as an oral
      solution. RESULTS: Endoscopic examinations showed grade 3 esophagitis in 26 of
      these patients according to Kuwahata's score. Twenty-five patients with grade 3
      esophagitis were given rhGM-CSF therapy. Radiotherapy was continued in 23
      patients. After the rhGM-CSF therapy, esophagitis had regressed from grade 3 to
      grade 0 in 10 (43%), from grade 3 to grade 1 in 8 (35%), and from grade 3 to
      grade 2 in 3 patients (12%). Two patients (9%) did not respond to rhGM-CSF
      therapy. Twenty-one patients (91%) completed planned radiotherapy without
      interruption. CONCLUSIONS: In patients with radiation-induced esophagitis,
      ulcerated esophageal mucosa healed with local granulocyte macrophage-colony
      stimulating factor administration in median 8 days without radiotherapy
      interruption.

PMID- 14571723
TI  - Peripheral blood mononuclear cells are possible extrahepatic replication sites
      for hepatitis C virus.
AB  - BACKGROUND/AIMS: Hepatitis C virus is a major causative agent of chronic liver
      disease and hepatocellular carcinoma and is considered to be a hepatotropic
      virus. It remains controversial whether hepatitis C virus exists in peripheral
      blood mononuclear cells and replicates there. In order to resolve this issue, we
      performed nested RT-PCR (reverse transcription polymerase chain reaction) and RT
      PCR in situ hybridization in peripheral blood mononuclear cells of patients with
      chronic hepatitis C. METHODOLOGY: We collected peripheral blood mononuclear cells
      from patients with chronic hepatitis C, extracted total RNA from the samples, and
      performed nested RT-PCR to detect hepatitis C virus RNA in the peripheral blood
      mononuclear cells lysates. We also fixed peripheral blood mononuclear cells of
      the patients in 4% paraformaldehyde and performed RT-PCR in situ hybridization
      with a digoxigenin-labeled RNA probe to detect hepatitis C virus RNA in the
      cells. RESULTS: Using these methods, we detected both positive- and negative
      stranded hepatitis C virus RNA in peripheral blood mononuclear cells of hepatitis
      C patients. To determine in which cell population of peripheral blood mononuclear
      cells hepatitis C virus is present, we performed PCR in situ hybridization after
      incubation with fluorescent latex microbeads which could be phagocytozed by
      monocytes. We obtained positive signals of the replicative hepatitis C virus
      genome not only in lymphocytes but also in monocytes. CONCLUSIONS: RT-PCR in situ
      hybridization with a nonradioactive probe was found to be useful for in situ
      detection of hepatitis C virus RNA. Our findings suggest that peripheral blood
      mononuclear cells may be extrahepatic replication sites for hepatitis C virus.

PMID- 14571724
TI  - Expression of transforming growth factor-alpha and epidermal growth factor
      receptor mRNA in the gastric mucosa of portal hypertensive rats.
AB  - BACKGROUND/AIMS: TGF-alpha (transforming growth factor-alpha) is a polypeptide
      that binds to the epidermal growth factor receptor and may play a role in gastric
      epithelial proliferation as well as the repair of injured gastric mucosa. Our
      previous studies have demonstrated that gastric mucosa TGF-alpha and epidermal
      growth factor receptor were significantly increased in rats with portal
      hypertension using the immunohistochemical analysis. Thus, the present study
      aimed to confirm the effect of portal hypertension on the expression of gastric
      TGF-alpha and epidermal growth factor receptor mRNA and to localize gastric TGF
      alpha and epidermal growth factor receptor mRNA production sites in rats.
      METHODOLOGY: Portal hypertension was induced experimentally by partial ligation
      of the portal vein in 12 male Wistar rats (PVL group), and in another group of 12
      rats (control) that received sham operations. The severity of gastric mucosal
      lesions was evaluated macroscopically by a gross ulcer index. We simultaneously
      detected the expression of TGF-alpha and epidermal growth factor receptor mRNA in
      the gastric tissues of control and portal hypertensive rats by the reverse
      transcription-polymerase chain reaction and in situ hybridization. RESULTS: The
      portal pressure and gross gastric mucosal damage differed significantly between
      the PVL group and the control group (p < 0.001 and p = 0.001, respectively). The
      expression of TGF-alpha and epidermal growth factor receptor mRNA was
      significantly increased in portal hypertensive rats compared to the control using
      the reverse transcription-polymerase chain reaction (both p < 0.01).
      Additionally, in situ hybridization showed the TGF-alpha and epidermal growth
      factor receptor mRNA were more intense in the PVL group compared to the control.
      TGF-alpha mRNA was located primarily in the parietal cells of the gastric fundic
      glands and in the surface epithelial cells, whereas epidermal growth factor
      receptor mRNA was mainly in the mucous neck cells of the proliferative zone and
      some parietal cells. CONCLUSIONS: From these findings, we suggest that the
      enhanced TGF-alpha and epidermal growth factor receptor production may play an
      important role in the gastric mucosal regeneration of portal hypertensive rats
      through the increased mRNA expression.

PMID- 14571725
TI  - Localization of T and B lymphocytes in histologically normal adult human donor
      liver.
AB  - BACKGROUND/AIMS: Donor liver suitable for successful transplantation often has
      one or more of a range of mild abnormalities including inflammation. Passenger
      leukocytes documented in donor liver are thought to result from inflammatory
      stimuli in response to ischemic, drug or alcohol related damage. The aim was to
      identify donor livers, which were free of any evidence of damage, and to
      determine if, and where, leukocytes were present in these pristine livers.
      METHODOLOGY: Eight of eighteen donor livers, examined by hematoxylin and eosin
      staining, were found to be free of any evidence of pathological damage. Sections
      from these livers were stained with antibodies against CD3 (T cell marker), CD20
      (B cell marker) and CD45 (common leukocyte antigen). RESULTS: Each of these
      livers were found to have significant numbers of T lymphocytes, located mainly in
      the portal tracts but also scattered throughout the parenchyma. A similar
      distribution of B cells was detected but at much lower levels. CONCLUSIONS: The
      presence of lymphocytes in the human liver is usually considered a hallmark of
      pathology. The demonstration of significant lymphocyte populations in pristine
      liver, particularly in the parenchyma, supports the hypothesis that the human
      liver harbors tissue-resident lymphocytes.

PMID- 14571726
TI  - Immunohistochemical microvessel count is not a reliable prognostic predictor in
      colorectal carcinoma.
AB  - BACKGROUND/AIMS: Immunohistochemical microvessel count for angiogenesis is
      associated with the growth and metastasis of various solid tumors, but its role
      in colorectal carcinoma remains controversial. This study aimed to determine its
      role in predicting the relapse and survival of colorectal carcinomas after
      curative surgery. METHODOLOGY: Representative paraffin-embedded sections of
      invasive colorectal cancers from 104 patients were studied by immunohistochemical
      staining using polyclonal anti-factor VIII antibody. Two investigators examined
      the microvessel count in the hot spot area of tumor using a 400x field in a blind
      fashion. RESULTS: There was no correlation between microvessel count and tumor
      size, location of carcinoma, tumor cell differentiation and nodal status. The
      microvessel count appeared to be lower among advanced-stage cancers as compared
      with early-stage cancers (pN0 vs. pN1+ pN2: 56 +/- 25. vs. 50 +/- 20; Dukes A + B
      vs. C + D: 56 +/- 25 vs. 49 +/- 18). In node-negative patients, the value of
      microvessel count greater than or equal to 75 seemed to correlate with longer
      disease-free survival and overall survival. CONCLUSIONS: Based on these results,
      immunohistochemical microvessel count seemed to decrease as colorectal cancer
      progressed and was not a reliable prognostic predictor in colorectal carcinoma.

PMID- 14571727
TI  - Concomitant analysis of p16/INK4, cyclin D1, and retinoblastoma protein
      expression in esophageal squamous cell carcinoma.
AB  - BACKGROUND/AIMS: Cyclin D1 expression is one of the important biologic factors
      and its close association with p16/INK4 and retinoblastoma protein expression has
      been proven in patients with esophageal squamous cell carcinoma, however, the
      clinical implication of these associations is still unknown. The objective of
      this study is to clarify its clinical significance. METHODOLOGY: We studied p16,
      cyclin D1, and pRB expression using immunohistochemistry in the resected
      specimens of 156 patients who underwent curative esophagectomy. RESULTS:
      Alteration of p16 expression, positive cyclin D1 expression and loss of pRB
      expression were demonstrated in 108 (69%) patients, 47 (30%) patients, and 48
      (31%) patients, respectively. An inverse correlation was found between p16
      expression and pRB expression (P < 0.0001). Of 47 cyclin D1-positive tumors, 39
      (83%) tumor exhibited alteration of p16 and 43 (92%) tumors were positive for
      pRB. Based on p16, cyclin D1, and pRB expression, 138 (88%) patients were divided
      into the following three groups: p16-/cyclin D1+/pRB+ (n = 44), p16+/cyclin D1
      /pRB- (n = 38), p16-/cyclin D1-/pRB+ (n = 56). The three groups were the most
      influential prognostic factors in a Cox's proportional regression model. The p16
      /cyclin D1+/pRB+ group had frequent hematogenous recurrence, while the other
      groups had frequent lymph node recurrence. CONCLUSIONS: Assessment of p16, cyclin
      D1, and pRB expression may be helpful for determining postoperative therapeutic
      strategies in patients with esophageal squamous cell carcinoma.

PMID- 14571728
TI  - Mesohepatectomy, caudate lobectomy and resection of hilar bifurcation with
      biliary reconstruction by 6 hepaticojejunostomies for Klatskin tumor.
AB  - We describe the technique of mesohepatectomy including caudate lobectomy and
      resection of hilar bifurcation with biliary reconstruction by 6
      hepaticoejunostomies for a Klatskin tumor type IV. This technically demanding
      approach does not only require careful vascular dissection to maintain blood
      supply and venous drainage of the two remaining liver parts but it also bears the
      risks of bilateral biliary reconstruction and of two resection surfaces. The
      major advantage of mesohepatectomy in comparison to extended hepatectomy is the
      preservation of functioning liver tissue. Therefore, despite its technical
      challenges, mesohepatectomy may be an attractive alternative in selected cases of
      advanced hilar cholangiocarcinoma in which an extended liver resection is
      contraindicated due to the small amount of remaining liver tissue. In these cases
      mesohepatectomy reduces the risk for postoperative liver insufficiency but still
      allows oncologic tumor resection.

PMID- 14571729
TI  - Esophageal cancer associated with the right aortic arch: a case study.
AB  - A case of esophageal cancer associated with the right aortic arch in a 62-year
      old Japanese male is described herein. Endoscopy performed after an initial
      complaint of dysphagia revealed cancer at the upper third of the esophagus. The
      right aortic arch was located by routine chest X-ray and an irregularly-shaped
      tumor defect and a shadow defect due to right aortic arch were detected on the
      right side of the thoracic esophagus by barium study. Computed tomography and
      magnetic resonance imaging offered useful information for surgical procedure. The
      patient underwent a subtotal esophagectomy and regional lymphadenectomy though a
      left thoracotomy. The clinical features of cases previously reported in Japan are
      reviewed following the presentation of this case.

PMID- 14571730
TI  - Malignant metastatic melanoma of common bile duct: virtual CT cholangioscopy
      findings.
AB  - Metastases from melanoma to biliary ducts are little known but not so rare,
      although only a few cases have been previously described. A case of metastasis
      from amelanotic melanoma to the common bile duct, appearing as a vegetating
      lesion and diagnosed by spiral computed tomography, using also computed
      tomography virtual cholangioscopy, is described. The clinical role of computed
      tomography virtual cholangioscopy is discussed. Metastases from melanoma are
      recommended to be considered in differential diagnosis of endoluminal soft masses
      in the biliary ducts.

PMID- 14571731
TI  - Solitary splenic metastasis derived from esophageal cancer.
AB  - Solitary splenic metastasis from esophageal cancer is so rare that such an
      occurrence in our Japanese patient should be reported. In a 58-year-old Japanese
      man we detected a solitary splenic tumor by abdominal computed tomography done 6
      months after he had undergone an esophagectomy. Transarterial embolization of the
      splenic artery was without effect. A splenectomy was then done and histological
      examination of the resected specimen revealed squamous cell carcinoma derived
      from the esophageal carcinoma.

PMID- 14571732
TI  - Prochlorperazine-induced cholestasis in a patient with alpha-1 antitrypsin
      deficiency.
AB  - A case of a 58-year-old woman with history of bilateral lung transplant secondary
      to alpha-1 antitrypsin deficiency (PIZZ), who presented with a severe drug
      induced cholestasis secondary to prochlorperazine is reported. After 27 months of
      prochlorperazine use, she developed liver failure consisting of jaundice with
      ascites. Computed tomography of the abdomen, abdominal ultrasonography as well as
      an endoscopic retrograde cholangiopancreatography showed no evidence for biliary
      obstruction. Liver biopsy demonstrated diffuse ongoing advanced chronic
      cholestasis, moderate portal and periportal inflammation as well as bridging
      fibrosis. During her hospitalization, her total bilirubin increased to 38.6
      mg/dL; alkaline phosphatase to 362 IU/L, alanine aminotransferase to 71 IU/L and
      aspartate aminotransferase to 88 IU/L. After several weeks of ursodiol therapy
      without clinical improvement the prochlorperazine was discontinued and was
      followed by a rapid improvement in her measures of liver injury. An immediate
      decline of her serum total bilirubin and alkaline phosphatase to 21.4 mg/dL and
      258 IU/L, respectively, occurred strongly suggesting the idea of a
      prochlorperazine-induced injury.

PMID- 14571733
TI  - Smallest cystic tumor, measuring 5 mm, was identified as an invasive
      adenocarcinoma among multiple intraductal papillary-mucinous tumors.
AB  - We encountered a case of four cysts of intraductal papillary-mucinous tumor in
      the pancreas, a 25-mm diameter tumor, a 20-mm tumor, and a 10-mm tumor in the
      pancreatic body and tail, and a 5-mm diameter tumor in the uncinatus process, and
      the smallest diameter intraductal papillary-mucinous tumor (5 mm) was regarded as
      an invasive papillary adenocarcinoma, while the other three intraductal papillary
      mucinous tumors were adenomas. A 63-year-old asymptomatic male was indicated of
      the presence of multiple pancreatic tumors by computed tomography during a
      physical examination. Endoscopic retrograde cholangiopancreatography revealed
      three cysts (25 mm, 20 mm, 10 mm diameter tumor) in the pancreatic body and tail,
      and one cyst 5 mm) in the uncinatus process. Cytologic examination of the
      pancreatic juice determined them as Class V. Based on a diagnosis of malignant
      intraductal papillary-mucinous tumors, he underwent distal pancreatectomy with
      removal of the uncinatus process. Pathologically, three cysts in the body and
      tail of the pancreas were found to be adenomas, but the 5-mm cyst in the
      uncinatus process was found to be an invasive intraductal papillary-mucinous
      tumor. The interstitium had been invaded by cancer, and the uncinatus process was
      the cancer positive surgical margin, and cystological examination of the
      pancreatic juice through repeated endoscopic retrograde cholangiopancreatography
      resulted in a class V, so the patient underwent a total pancreatectomy. When
      diagnosing intraductal papillary-mucinous tumor(s), there is the possibility of
      incorrectly differentiating between benignancy and malignancy when the diagnosis
      is based on cyst diameter, as is conventional.

PMID- 14571734
TI  - Ultrasonographic diagnosis of inflammatory pseudotumor of the ileum complicating
      with intussusception: a case report.
AB  - Inflammatory pseudotumor is one of the etiologies that may cause small bowel
      intussusception. Because of its emergency, early diagnosis plays a pivotal role
      in successful management. Ultrasonography is a safe and handy diagnostic tool
      without invasiveness and it is advantageous for early preoperative diagnosis. We
      present a case of ileal intussusception caused by inflammatory pseudotumor, which
      was diagnosed preoperatively with ultrasonography and was proven by operation.
      The ultrasonographic feature of the inflammatory pseudotumor was heterogeneously
      hyperechoic and it should be included in the differential diagnosis of
      hyperechoic leading lesions of small bowel intussusception in adults.

PMID- 14571735
TI  - Quality of life after laparoscopic or open colonic resection for cancer.
AB  - BACKGROUND/AIMS: Although laparoscopic colectomy has been widely accepted, little
      is known about the subjective clinical results of this less invasive surgery. The
      aim of this study was to evaluate the quality of life of patients who had
      undergone laparoscopic or open colonic resection for cancer. METHODOLOGY: The
      study included 26 patients with laparoscopic colectomy and 87 with conventional
      open colectomy for cure of colon cancer. Body temperature, serum C-reactive
      protein and albumin levels, lymphocyte count, and weight loss during hospital
      stay were compared between the two groups. Quality of life was estimated by the 9
      item questionnaire with scoring system of 1 (high), 2 (fair), and 3 (low).
      RESULTS: Laparoscopic colectomy was significantly different from open colectomy
      with regard to the body temperature (37.8 degrees C vs. 38.0 degrees C, p < 0.01)
      and C-reactive protein level (6.34 mg/dL vs. 11.15 mg/dL, p < 0.01) on
      postoperative day 1, albumin level (3.54 g/dL vs. 3.36 g/dL, p < 0.05) and
      lymphocyte count (1354/mm3 vs. 995/mm3, p < 0.01) on postoperative day 7, and
      weight loss on postoperative day 14 (3.95% vs. 5.45%, p < 0.01). Although all
      patients with laparoscopic colectomy were satisfied with their surgical results,
      total score of the quality-of-life questionnaire was not significantly different
      between the two groups (10.95 vs. 11.81). Both laparoscopic and open colonic
      resections were similarly accepted by the patients as a good operation that they
      would recommend to others (1.105 vs. 1.206). CONCLUSIONS: These results indicate
      that although laparoscopic colonic resection for cancer was less invasive than
      conventional open colectomy, both laparoscopic and open colonic resections were
      favorably accepted by the patients, and quality of life after operation was not
      significantly different between the two procedures.

PMID- 14571736
TI  - Effects of octreotide and propranolol on colonic mucosa in rats with portal
      hypertensive colopathy.
AB  - BACKGROUND/AIMS: The aim of the study is to clarify the effects of octreotide and
      propranolol, agents used in the treatment of portal hypertension, on mucosal
      changes in portal hypertensive colopathy. METHODOLOGY: Portal hypertension was
      induced in all rats by partial portal vein ligation, and after the operation all
      rats were caged for a 10-week period. Then, animals were divided into three
      groups and for two weeks medical treatment were administered to the individual
      groups as follows: Control group, saline 0.5 mL/day, intraperitoneally.
      Octreotide group, octreotide 100 micrograms/kg/12 hours, subcutaneously.
      Propranolol group, propranolol 20 mg/kg/day, intraperitoneally. In order to
      assess the portal hypertensive colopathy, criteria such as mean diameters of
      dilated vessels in colonic mucosa, and the existence of mucosal edema, capillary
      ectasia, hyperemia and hemorrhage, inflammation were used. RESULTS: When
      parameters were compared for the control versus propranolol groups, mucosal edema
      and hyperemia and hemorrhage criteria were found to be significant for the
      propranolol group; control versus octreotide groups, mucosal edema, capillary
      ectasia, and hyperemia and hemorrhage criteria were found to be significant for
      the octreotide group; octreotide versus propranolol groups, capillary ectasia and
      mucosal edema criteria were found to be significant for the octreotide group.
      CONCLUSIONS: The mucosal changes in portal hypertensive colopathy could be
      corrected by drugs modifying portal blood flow, octreotide may find a place in
      the treatment of portal hypertensive colopathy.

PMID- 14571737
TI  - A prognostic score for colorectal cancer.
AB  - BACKGROUND/AIMS: Scoring systems are generally used for predicting prognosis in
      critically ill patients, but not frequently for predicting prognosis in cancer.
      Our aim was to develop a prognostic score for colorectal cancer. METHODOLOGY:
      Demographic, clinical, laboratory, radiologic, histopathologic and operative data
      of 112 patients who had resection for colorectal cancer, were analyzed for their
      effect on survival. Eight variables (invasion depth of tumor, nodal status,
      presence of metastasis, CEA level, differentiation, resectability, tumor
      location, presence of blood transfusion), which have the most significant effect
      on survival in univariate analysis and multivariate analysis, were chosen.
      Coefficients were calculated and the Prognostic Score for Colorectal Cancer
      (PSCRC) was designed. All patients were scored using this system and staged
      according to TNM, Dukes and Astler-Coller systems. RESULTS: The score range is
      between -49 and 80. Patients were grouped as Group 1 (score < -30), Group 2
      (score -30 to -6), Group 3 (score -5 to 19), Group 4 (score > 19). Survival rates
      decreased and recurrence rates increased significantly with increasing scores.
      The associations of PSCRC and staging systems with survival and recurrence rates
      were determined by logistic and Cox regression analyses. PSCRC was proved to have
      the most significant association with survival and recurrence rates. Furthermore,
      PSCRC had better correlation with survival and recurrence rates when compared
      with staging systems according to Pearson correlation analysis. CONCLUSIONS:
      Inclusion of more variables in PSCRC seems to make it superior to the staging
      systems. PSCRC may be a practical and useful scoring system in clinical practice
      and is easily adapted to different patient populations.

PMID- 14571738
TI  - Recurrence patterns after curative resection of colorectal cancer in patients
      followed for a minimum of ten years.
AB  - BACKGROUND/AIMS: To investigate the recurrence patterns and interval from initial
      surgery in patients with curatively resected colorectal cancer followed for a
      minimum of 10 years. METHODOLOGY: We retrospectively reviewed 418 patients who
      had undergone curative resection for colon cancer (n = 246) or rectal cancer (n =
      169). Follow-up periods ranged from 10 to 23 years. Main outcome measures were
      interval until recurrence, site of first recurrence, and influence of adjuvant
      chemotherapy. RESULTS: 26 (6%) had been lost to follow-up by 10 years and 143
      (34%) had died. The most common site of recurrence was liver in colon cancer and
      locoregional in rectal cancer. The cumulative recurrence rate in colon cancer was
      100% at 4 years. In rectal cancer, it was 89% at 5 years, 98% at 7 years and 100%
      at 10 years. The interval until recurrence was longer in rectal cancer (26.0 +/-
      24.2 months) than in colon cancer (17.1 +/- 11.0 months) (p = 0.03). It was also
      longer in patients receiving than in those not receiving adjuvant chemotherapy (p
      < 0.01). The interval until lung metastasis was longer than that until liver
      metastasis in colon cancer (p = 0.04), and longer than that until locoregional
      recurrence in rectal cancer (p = 0.03). The interval until recurrence in the
      colon cancer was shorter for stage III than for stage II (p = 0.02). CONCLUSIONS:
      Surveillance for recurrences, particularly for relapses in the liver and lung,
      should be performed for at least 4 years in colon cancer patients. Patients with
      rectal cancer should be followed for a longer period than those with colon
      cancer, focusing on locoregional, liver and lung recurrence. It is particularly
      noteworthy that adjuvant chemotherapy may prolong the interval until recurrence
      and the interval until lung metastasis is relatively longer.

PMID- 14571739
TI  - Sandostatin as a "hormonal" temporary protective ileostomy in patients with total
      or subtotal colectomy.
AB  - BACKGROUND/AIMS: We describe our experience with the use of a new method of so
      called "hormonal" ileostomy by using Octreotide, a long-acting analog of the
      inhibitory peptide Somatostatin (Sandostatin Novartis), aiming to advocate
      protective ileostomy or colostomy, in patients who underwent total or subtotal
      colectomy for ulcerative colitis or obstruction of left colon, due to carcinoma
      or diverticulitis. METHODOLOGY: "Hormonal" protective ileostomy by using
      Sandostatin (Novartis) was performed in 10 patients after subtotal colectomy for
      ulcerative or left colon obstruction without a protective ileostomy or colostomy.
      Sandostatin 0.5 mg/mL was given from the day of operation to the 10th
      postoperative day, in a dose of 2 x 3 per day subcutaneously. The time of return
      of peristalsis, number of bouts of diarrhea and postoperative complications were
      evaluated. RESULTS: The patients were classified in two groups: First group (40%
      of all patients) with bowel obstruction and second group (60% of all patients)
      with ulcerative colitis. In the first group the mean time of return of
      peristalsis was 4.5 days and the mean number of bouts of diarrhea was 4.2 per
      day. One patient was reoperated for intraabdominal abscess and the morbidity was
      50% with minor postoperative complications. In the second group the mean time of
      peristalsis return was 5 days and the mean number of bouts of diarrhea was 5.4
      per day. One patient was reoperated for intestinal bleeding and the morbidity was
      60% with minor postoperative complications. CONCLUSIONS: The use of Octreotide
      appears to serve as a useful adjunctive and important role in controlling
      intestinal output, so that it is an available method of "hormonal" protective
      ileostomy in very low rectal or anal anastomosis, by avoiding a second operation
      for ileostomy or colostomy closure and reducing the median hospital stay and
      total socioeconomic cost.

PMID- 14571740
TI  - Evolution of the changes of the ileal pouch mucosa over a long follow-up period.
AB  - BACKGROUND/AIMS: The mucosa of the ileal pouch after restorative proctocolectomy
      develops relevant adaptative changes but the real mechanisms and the evolution
      over time of these alterations are still unclear. The aims of the present work
      were to study the distribution of the mucosal changes at different levels in the
      reservoir and to evaluate the evolution of these alterations over a long follow
      up period. METHODOLOGY: The severity of chronic and acute inflammation, villous
      atrophy, colonic-type mucins production and proliferative index were evaluated in
      the bioptical specimens from 46 patients (30 males, 16 females, mean age 38
      years) with functioning pouch. We compared the histology of the upper pouch
      mucosa with the lower one. Then we divided the 46 patients into Group A-24
      patients with a median follow-up of 11 years (range 9-16); Group B-22 patients
      with a median follow-up of 4 years (range 2-8), comparing the results from the
      two groups. Finally we performed a prospective evaluation in the 24 patients who
      were controlled in 3 subsequent follow-ups (1993-1994, 1996-97, 1999-2000).
      RESULTS: At the topographic evaluation only the acute inflammation was
      significantly more pronounced in the lower pouch area (p = 0.031). All the
      morphological changes showed a trend of greater severity in the group A patients,
      in particular villous atrophy (p = 0.005) and colonic-like mucins secretion (p =
      0.006). At the prospective evaluation, the chronic inflammation showed a
      significant progressive worsening over time (p = 0.011). CONCLUSIONS: Our
      experience showed that the transformation of the mucosa represents an "organ"
      response to the luminal environment and may progress over time.

PMID- 14571741
TI  - Prospective study of the functional results of transanal endoscopic microsurgery.
AB  - BACKGROUND/AIMS: Most clinical research addresses the technological advances and
      oncological outcomes of transanal endoscopic microsurgery. Our aim was to examine
      the functional results. METHODOLOGY: From August 1999 to November 2000, 22
      Taiwanese patients (14 men, 8 women; median age, 68 years) undergoing transanal
      endoscopic microsurgery were prospectively examined. Functional questionnaires
      and anorectal manometry were assessed before surgery and at 2 weeks, 6 weeks, 3
      months, and 1 year. RESULTS: The median distance from the anal verge to the tumor
      was 10 cm. The median tumor diameter was 2.0 cm. The median duration of surgery
      was 120 minutes. No surgical mortality or morbidity and no local recurrence
      occurred during a median follow-up of 23 months. The mean stool frequency and
      consistency were significantly better at 3 months after surgery than before
      surgery. The maximal resting pressure significantly decreased after surgery. The
      maximal contraction pressure and maximal tolerated volume were significantly
      lower at 2 and 6 weeks than before surgery; these values recovered at 1 year.
      CONCLUSIONS: Transanal endoscopic microsurgery is safe for the cure of benign
      tumors and the palliative excision of malignant tumors in middle and upper
      rectum. Anorectal function was preserved and improved, though some anorectal
      manometric parameters changed over time.

PMID- 14571742
TI  - Surgical technique influences bowel function after low anterior resection and
      sigmoid colectomy.
AB  - BACKGROUND/AIMS: Since June 1996, we have changed surgical strategies to preserve
      the pelvic autonomic nerve and abandon high ligation of the inferior mesenteric
      artery. The aim of this study was to clarify the influence of this surgical
      technique on subjective bowel function of patients with low anterior resection
      and sigmoid colectomy for cancer. METHODOLOGY: Forty-eight patients who underwent
      low anterior resection or sigmoid colectomy for cancer during June 1996 and
      February 2000 replied to the questionnaire which consisted of eight categories of
      bowel symptoms. Subjective bowel function and operative data of these patients
      were compared with those obtained from 84 patients with low anterior resection or
      sigmoid colectomy during April 1984 and May 1996. RESULTS: When recent series
      were compared with previous series, the frequency of bowel movement at night (21%
      vs. 60%, p < 0.01) and patient's own judgment as fair or poor (0% vs. 29%, p <
      0.01) was decreased in patients with low anterior resection; whereas the
      frequency of defecation > 2 per day (5% vs. 34%, p < 0.01), difficulty in
      emptying (32% vs. 71%, p < 0.01), and incomplete evacuation (32% vs. 66%, p <
      0.05) was decreased in patients with sigmoid colectomy. Patient judged as poor
      bowel function was less frequent in the recent group after low anterior resection
      (25% vs. 71%, p < 0.01) and sigmoid colectomy (18% vs. 42%, p < 0.05) compared
      with the previous group. Operative data including volume of blood loss, frequency
      of transfusion, and length of resected specimen were also different between the
      two groups. CONCLUSIONS: Surgical technique had a significant impact on bowel
      function following low anterior resection and sigmoid colectomy for cancer. When
      high ligation of the inferior mesenteric artery is abandoned and the pelvic
      autonomic nerve is preserved by careful technique, postoperative bowel
      dysfunction in patients with rectosigmoid colon cancer can be minimized.

PMID- 14571743
TI  - Effects of propionyl-L-carnitine topical irrigation in distal ulcerative colitis:
      a preliminary report.
AB  - BACKGROUND/AIMS: To study the tolerability of propionyl-L-carnitine administered
      as rectal irrigation and its efficacy in improving the clinical picture of distal
      ulcerative colitis. METHODOLOGY: Ten male subjects (aged 18 to 55 years, with a
      body mass index ranging from 21 to 25 Kg/m2) with distal ulcerative colitis were
      treated with propionyl-L-carnitine enemas (6 g in 200 mL physiological solution)
      twice a day over 120 minutes each. All subjects had a disease activity index from
      0 to 1. A clinical, laboratory, endoscopy and biopsy evaluation was performed at
      baseline and 14 days after treatment. Serum tumor necrosis factor-alpha and
      interleukin-2 concentration was measured. RESULTS: No side effects were reported
      by the entire patient population and the clinical conditions remained constant
      throughout the study period. The disease activity index improved significantly
      between the beginning and the end of the study in 80% of the patients. Histologic
      features (mucosal erosion, distortion of crypt architecture, inflammation and
      lamina propria gap) significantly improved in all treated patients. Serum
      interleukin-2 levels did not change significantly after propionyl-L-carnitine
      treatment (respectively: 14.7 +/- 15.8 before vs. 9.9 +/- 13.2 pg/mL), while
      tumor necrosis factor-alpha levels were undetectable both before and after
      propionyl-L-carnitine administration. CONCLUSIONS: The topical treatment with a
      new formulation containing propionyl-L-carnitine seems to be safe and effective
      in improving the histologic features in patients with inactive or mild ulcerative
      colitis, as an alternative to conventional therapy.

PMID- 14571744
TI  - Clinicopathologic significance of immunohistochemical fecal occult blood test in
      subjects receiving bidirectional endoscopy.
AB  - BACKGROUND/AIMS: Fecal occult blood test has been utilized to screen for lower
      gastrointestinal pathologies, such as colorectal cancer and polyps that bleed.
      Recent studies have revealed a relatively high frequency of upper
      gastrointestinal abnormalities in subjects with positive fecal occult blood by
      guaiac-based method. Although immunohistochemical tests of fecal occult blood
      were assumed to have greater diagnostic validity, the distribution of
      gastrointestinal pathology using such examinations is not well established. This
      study aims to investigate the efficacy of immunohistochemical analysis of fecal
      occult blood in detecting upper and lower gastrointestinal lesions in
      asymptomatic individuals. METHODOLOGY: Subjects who underwent regular health
      checkups were enrolled if they received both esophagogastroscopic and
      colonoscopic examinations. Each subject was tested by an immunohistochemical
      fecal occult blood test. The fecal occult blood results were evaluated and
      correlated with lesions identified in endoscopic examinations. RESULTS: In total
      655 males and 722 females with age 46.2 +/- 12.1 years were enrolled, 287 cases
      (20.7%) had polypoid lesions of colon, including 6 colon cancers, 37 with polyps
      > or = 1 cm, 104 with polyp 5-9 mm, and 140 with polyp < 5 mm. FOB was positive
      in 31 cases, of which 15 (15/31, 48.4%) were polypoid lesions of colon, 1 was
      colonic ulcer, 9 (29.0%) were active gastroduodenal ulcers but 6 (19.4%) had no
      significant lesions. The positive and negative predictive value for colon polyps
      was 48.4% and 80%, respectively. The sensitivity was 50% (3/6) for colon cancer
      and varied among polyps with different sizes: 16.2% (6/37) for polyps > or = 1
      cm; 5.8% (6/104) for polyps 5-9 mm and 0% (0/140) for polyps < 5 mm. CONCLUSIONS:
      A substantial portion of subjects (29%) with positive fecal occult blood reaction
      of immunohistochemical analysis but negative colonoscopy still needs
      esophagogastroscopic examination to disclose upper gastrointestinal lesions.
      Immunohistochemical determination of fecal occult blood remains imperfect for
      polypoid lesions of colon in view of its sensitivity and specificity.

PMID- 14571745
TI  - Successful resection of locally advanced rectal carcinoma combined with
      preoperative chemoradiation.
AB  - Chemoradiation increases the local control and colostomy-free survival in
      patients with advanced anal canal carcinomas. We recently experienced a 50-year
      old female patient with locally advanced carcinoma of the rectum invading to the
      sacrum, which could not be surgically resected. Therefore, we performed a
      colostomy and transarterial infusion of anti-tumor drugs including 50 mg
      cisplatin and 10 mg mitomycin C via the inferior mesentery artery in September
      1999. She then underwent radiotherapy with a total dose of 64 Gy for the primary
      tumor. After the radiotherapy the patient received 125 mg/body of 1-leucovorin by
      2-hour infusion and, one hour after starting the 1-leucovorin infusion, she
      received an intravenous bolus of 250 mg/body of 5-fluorouracil. This regimen was
      conducted biweekly for 13 courses followed by oral administration of 400 mg 5'
      deoxyfluorouridine for one year. Since the chemoradiation resulted in a
      successful response, the patient underwent curative resection of the primary
      tumor in June 2001. The resected tumor (32 x 35 mm) had clean margins. Although
      the carcinoma cells had disappeared, fibrous lesions were observed over a broad
      area. Based on these pathologic findings, the treatment effect was judged as
      grade Ib.

PMID- 14571746
TI  - Simple closure of chronic duodenal ulcer perforation in the era of Helicobacter
      pylori: an old procedure, today's solution.
AB  - BACKGROUND/AIMS: To evaluate the risk of recurrence in our patients with chronic
      duodenal ulcer perforation, who underwent a simple closure and postoperative
      Helicobacter pylori eradication therapy. METHODOLOGY: Within 4.5 years (3/1996 to
      7/2000), 21 patients with chronic duodenal ulcer perforation, were operated in
      our hospital. All of them underwent simple closure with omental patch repair plus
      Helicobacter pylori eradication with omeprazole, clarithromycin and amoxycillin
      for two weeks. On December 2000, in 14 (66.6%) of these patients, urea breath
      test for Helicobacter pylori was performed, followed by endoscopy. RESULTS: The
      mean age of our 14 patients is 55 years. The urea breath test was positive for
      Helicobacter pylori in 3 (21.4%) patients. Two of them had endoscopically
      gastritis, confirmed by pathological examination. None of our patients had ulcer
      relapse. The three patients with positive urea breath test received another
      course of the same eradication therapy. CONCLUSIONS: Simple closure of perforated
      chronic duodenal ulcer in combination with postoperative Helicobacter pylori
      eradication, seems to be an accepted treatment, so the immediate acid-reduction
      surgery (vagotomy) in the contaminated environment caused by perforation, is
      probably unnecessary.

PMID- 14571747
TI  - "Duodenal intussusception" due to adenoma of the papilla of Vater.
AB  - The case of a 55-year-old woman with a pedunculate adenoma of the papilla of
      Vater is presented. Diagnostic imaging modalities including ultrasonography, CT
      scan, magnetic resonance of cholangiopancreatography, simultaneous duodenography
      and cholangiography, and angiography showed a giant tumor protruding
      intraluminally and moving forward in the duodenum by peristalsis. It had a
      duodenal intussusception-like appearance, with remarkable left-lower deviation of
      the common bile duct and major pancreatic duct in the papilla of Vater as far as
      the left side of the aorta. Episodes of jaundice or ileus were absent, probably
      because the tumor was mobile in the duodenum. As biopsy specimens showed no
      malignancy and intraductal ultrasonography in the common bile duct revealed no
      intraductal invasion of the tumor in the papilla of Vater, the patient underwent
      transduodenal papillectomy with papilloplasty with pancreatic ductoplasty.
      Pathological diagnosis of consecutive specimens was a papillary adenoma with
      moderate atypia and occasional tubular structure. There seems to be an
      exceptional subtype of the tumor in the papilla of Vater, like this case,
      demonstrating the duodenal intussusception-like appearance without prominent
      clinical symptoms.

PMID- 14571748
TI  - Clinical presentation of pulmonary edema following esophagectomy on chest
      radiograph.
AB  - BACKGROUND/AIMS: To determine whether the clinical presentation of pulmonary
      edema following esophagectomy can be objectively determined by changes in X-ray
      density in the lung field on chest radiography. METHODOLOGY: Sixteen patients who
      underwent esophagectomy for thoracic esophageal cancer and five patients who
      underwent less radical surgery at Akita University Hospital between July 2000 and
      March 2001 were recruited to the thoracic esophageal cancer and control groups,
      respectively. Chest radiography was carried out using five aluminum disks (15,
      20, 25, 30 and 35 mm thickness) placed in upper right corner of the film and X
      ray density for the disks and chest lung field was measured using a densitometer
      until POD 7. RESULTS: In the thoracic esophageal cancer group, X-ray density in
      the lung field, body weight, and respiratory index increased significantly in the
      immediate postoperative period. The X-ray density in the lung field peaked on POD
      2, and remained constant to POD 6. Correlations were found among changes in X-ray
      density in the lung field, body weight, and respiratory index. CONCLUSIONS: The
      measurement of X-ray density on a chest radiograph is useful for prediction as
      well as early management of patients with pulmonary edema following esophagectomy
      for thoracic esophageal cancer.

PMID- 14571750
TI  - Prophylactic transileocolic obliteration of esophageal varices after balloon
      occluded retrograde transvenous obliteration of gastric varices with a
      gastrorenal shunt.
AB  - Several non-surgical techniques have been developed to treat esophagogastric
      varices that occur secondary to portal hypertension, including those performed
      endoscopically or with interventional radiologic therapies. In patients with
      large gastric fundal varices and associated gastrorenal shunting, controversy
      still remains in defining the most appropriate non-surgical intervention. Balloon
      occluded retrograde transvenous obliteration has been shown to be one effective
      treatment for gastric varices in these instances. However, in the population
      treated in this manner, the inhibition of subsequent esophageal varices is
      essential. We report a patient with gastric fundal varices that were successfully
      treated using balloon-occluded retrograde transvenous obliteration and in whom
      prophylactic transileocolic obliteration of esophageal varices was additionally
      performed. This 46-year-old man was diagnosed with severe gastric varices and
      gastrorenal shunting with only mild esophageal varices. Five years after therapy,
      the patient demonstrates no evidence of recurrence of either gastric or
      esophageal varices and has remained otherwise healthy.

PMID- 14571749
TI  - Detection of lymph node micrometastasis in esophageal carcinoma.
AB  - BACKGROUND/AIMS: The presence of lymph node metastasis is the most important
      prognostic factor in esophageal squamous cell carcinoma. Molecular biology
      techniques have improved the ability to recognize micrometastasis in lymph nodes,
      bone marrow, and peripheral blood. Previous studies have demonstrated that
      cytokeratin 19 reverse transcriptasepolymerase chain reaction can detect tumor
      cells even when lymph nodes appear normal histologically. However, the presence
      of pseudogenes for cytokeratin 19 have reduced the specificity of reverse
      transcriptase-polymerase chain reaction, thereby reducing its clinical worth as a
      sensitive diagnostic technique. METHODOLOGY: We examined the expression of mRNA
      for cytokeratin 19 using a newly designed set of primers, and compared the
      results with data from histologic examinations. Samples were obtained from
      tumors, intact tissues, resected lymph nodes and in 10 patients who underwent
      esophagectomy via right thoracotomy with lymph node dissection in the neck,
      mediastinum and abdomen. RESULTS: All tumors, non-cancerous tissues were positive
      for cytokeratin 19 by reverse transcriptasepolymerase chain reaction. However, 2
      of the 6 lymph nodes that appeared normal on histologic examination were positive
      for cytokeratin 19; sensitivity and specificity were 100% and 67%, respectively.
      CONCLUSIONS: Reverse transcriptase-polymerase chain reaction using new primers
      for cytokeratin 19 detected micrometastasis in specimens of lymph nodes from
      patients with squamous cell carcinoma. This method may increase the accuracy of
      tumor staging and provide clinicians with valuable information that will help
      individualize treatment options.

PMID- 14571752
TI  - Open versus laparoscopic appendectomy.
AB  - BACKGROUND/AIMS: To asses the role of laparoscopic appendectomy in the treatment
      of acute as well as chronic appendicitis on the basis of our own experiences.
      METHODOLOGY: From the set of 849 patients treated with appendectomy (from January
      1993 to December 2000) 331 were singled out, i.e.; those unable to work for some
      time and thus being on sickness benefit who asked for a medical certificate. They
      were operated on for either acute or chronic appendicitis. RESULTS: In our set of
      331 patients (158 males, 173 females, the average age 29.4) open appendectomy was
      performed on 179 patients and laparoscopic appendectomy on 152. Laparoscopic
      appendectomy was performed in 43 males (28%) and 109 females (72%); open
      appendectomy in 115 males (64%) and 64 females (36%). Laparoscopic appendectomy
      took 53.7 +/- 18.1 minutes, open appendectomy took 43.6 +/- 8.99 minutes. The
      time of work disablement is longer in open appendectomy (open appendectomy: 41.2
      +/- 9.91 days; laparoscopic appendectomy; 29.1 +/- 15.11 days). A significant
      difference (p < 0.00001) can be seen in the length of hospitalization
      (laparoscopic appendectomy: 5.0 +/- 2.75 days, open appendectomy: 8.3 +/- 2.83
      days). CONCLUSIONS: Patients who undergo laparoscopic appendectomy spent less
      time in hospital, and they can return to work rather earlier. On the other hand
      the time of surgery is longer. Higher cost is compensated for with shorter
      hospitalization and early return to work.

PMID- 14571751
TI  - Bone mineral density in patients with small intestinal bacterial overgrowth.
AB  - BACKGROUND/AIMS: Malabsorption has long been recognized as a cause of osteopenia,
      and mild forms of osteopenia are present in many gastrointestinal disorders. The
      aim of this study was to determine if osteopenia is common in patients with small
      intestinal bacterial overgrowth. METHODOLOGY: Bone mineral density was measured
      in fourteen patients with small intestinal bacterial overgrowth. Patients with
      obvious structural predisposing conditions such as previous gastric operations,
      small bowel strictures and small bowel diverticula, were excluded. Measurements
      were made in the distal right radius and ulna, in the hip and in the spine. The
      results were compared to those of a reference population. Radiographs of the
      spine were assessed for evidence of vertebral fractures. Blood samples were
      analyzed for serum concentrations of 25-hydroxyvitamin-D3 and 1,25
      dihydroxyvitamin-D3, alkaline phosphatase activity, ionized calcium, intact
      parathyroid hormone and osteocalcin. All patients completed a questionnaire
      concerning, inter alia, previous fractures, past and current diseases, tobacco
      smoking and medication. RESULTS: Patients with small intestinal bacterial
      overgrowth had significantly low bone density in the femoral neck (p < 0.01) and
      in the lumbar spine (p < 0.05), compared to a reference population. Six of 14
      (43%) patients had had fractures. CONCLUSIONS: Patients with small intestinal
      bacterial overgrowth have low bone mineral density. In patients with osteopenia
      of unknown origin, small intestinal bacterial overgrowth should be considered.

PMID- 14571753
TI  - Does stapled functional end-to-end anastomosis affect recurrence of Crohn's
      disease after ileocolonic resection?
AB  - BACKGROUND/AIMS: Crohn's disease is characterized by a high incidence of
      perianastomotic recurrence after ileocolonic resection. The influence of
      anastomotic configuration on the incidence of reoperation was evaluated in
      patients undergoing resection for Crohn's disease. METHODOLOGY: 106 patients
      affected by ileocolonic Crohn's disease were divided in two groups: group I with
      a hand-sewn end-to-side or side-to-side isoperistaltic anastomosis (30 patients)
      and group II with functional end-to-end anastomosis made with linear staplers (76
      patients). RESULTS: The morbidity was 4.7%: 3 complications and a postoperative
      death occurred in group I and two complications occurred in group II. There were
      5 recurrences (16.7%) in the hand-sewn group and 2 recurrences (2.6%) in the
      stapled group, with a recurrence rate of 3.54 and 0.92, respectively.
      CONCLUSIONS: Our non-randomized study suggests a better trend toward the
      functional stapled technique, in terms of recurrence rate. These observations
      need further investigation with randomized controlled trials, to compare the two
      different anastomotic procedures.

PMID- 14571755
TI  - Immunohistochemistry and c-kit gene analysis in determining malignancy in
      gastrointestinal stromal tumors.
AB  - BACKGROUND/AIMS: Usefulness of immunohistochemistry and c-kit proto-oncogene
      mutation was examined for determining malignancy in 24 cases of gastrointestinal
      stromal tumors. METHODOLOGY: Cases were histologically diagnosed and subjected to
      immunohistochemical staining and c-kit gene analysis. All parameters were
      compared to prognosis. RESULTS: There were significant differences in tumor size,
      central necrosis, mitotic activity and histological diagnosis between recurrent
      and non-recurrent cases. Positivity to KIT staining was 100% in recurrent and
      87.5% in non-recurrent cases. Positivity to Ki-67 and p53 staining were
      significantly higher in recurrent cases than in non-recurrent cases. Mutations in
      exon 11 of the c-kit gene were significantly more frequent in recurrent cases
      than in non-recurrent cases. CONCLUSIONS: Histological diagnosis, tumor size,
      central necrosis, and mitotic activity were reconfirmed to be indicators for
      recurrence of gastrointestinal stromal tumors. Furthermore, it is suggested that
      positivity of Ki-67 and p53 immunostaining and c-kit gene mutation also need to
      be done for prediction of recurrence.

PMID- 14571754
TI  - Oral ciprofloxacin versus intravenous cefotaxime and ceftriaxone in the treatment
      of spontaneous bacterial peritonitis.
AB  - BACKGROUND/AIMS: Cefotaxime or ceftriaxone were considered the first-choice
      antibiotic for empirical treatment in cirrhotic patients developing spontaneous
      bacterial peritonitis. It has been suggested that ciprofloxacin could be an
      alternative to cefotaxime or ceftriaxone in cirrhotic patients developing
      spontaneous bacterial peritonitis. The aim of the present study was to compare
      oral ciprofloxacin with cefotaxime and ceftriaxone in the treatment of
      spontaneous bacterial peritonitis in cirrhotic patients. METHODOLOGY: Fifty-three
      hospitalized cirrhotic patients with spontaneous bacterial peritonitis were
      prospectively included and randomized into three groups: group A (n = 16);
      received orally 500 mg ciprofloxacin every 12 h, group B (n = 18); received
      intravenous cefotaxime 2 g every 8 h and group C (n = 19) received intravenous
      ceftriaxone 2 g every 24 h. RESULTS: 15 patients from the ciprofloxacin group, 17
      from the cefotaxime group and 17 patients from the ceftriaxone group were finally
      analyzed. Spontaneous bacterial peritonitis resolution in three groups was found
      to be 80%, 76%, and 83%, respectively (p = NS). Incidence of complications and
      hospital mortality was similar in the three groups. No adverse events were
      observed in any of the three groups. The cost of the treatment was statistically
      lower in the ciprofloxacin group than in the cefotaxime group and ceftriaxone
      group (p < 0.001). CONCLUSIONS: These results suggest that orally ciprofloxacin
      is as effective as cefotaxime and ceftriaxone in the empirical treatment of
      spontaneous bacterial peritonitis in cirrhotic patients, and is also less
      expensive and can be administered orally.

PMID- 14571756
TI  - The incidence of HLA DRB1*0103 in ulcerative colitis patients in north-eastern
      Poland.
AB  - BACKGROUND/AIMS: Susceptibility to inflammatory bowel disease is partially
      genetically determined and the HLA (human leukocyte antigen) alloantigens and
      genes located in the HLA region have been studied over the course of many years
      as the candidate genes responsible for ulcerative colitis. Improvements in
      molecular genotyping have allowed disease association with HLA to be narrowed
      down to specific subtypes. For class II antigens, increasing phenotype frequency
      of DRB1*0103, DRB1*1502 is observed and positive correlation to disease
      susceptibility is proposed. We investigated the incidence of HLA DRB1*0103 in
      ulcerative colitis patients in North-Eastern Poland and possible association with
      overall disease susceptibility and clinical course of the disease. METHODOLOGY:
      41 patients and 45 healthy control blood donors were included in this study. All
      subjects were Polish. RESULTS: The incidence of HLA DRB1*0103 was low (2.44%),
      but was associated with fulminant course of the disease (pancolitis with
      megacolon toxicum). None of the ethnically matched healthy control blood donors
      possessed the HLA DRB1*0103 allele (0.00%). CONCLUSIONS: The results gained in
      the presented study confirm, that in the Polish population HLA DRB1*0103 allele
      is uncommon and it would not be a useful marker of disease susceptibility.

PMID- 14571757
TI  - Radiolabeled leukocyte imaging in inflammatory bowel disease: a prospective
      blinded evaluation.
AB  - BACKGROUND/AIMS: Nuclear medicine scintigraphies have been reported to assist in
      making the diagnosis of inflammatory bowel disease. This work aimed to assess the
      role of radiolabeled leukocyte scintigraphy for the diagnosis of suspected
      inflammatory bowel disease. METHODOLOGY: Forty-six adult patients were referred
      for labeled leukocyte scintigraphy for the evaluation of active abdominal pain.
      The patient population included inpatients and outpatients, with known or
      suspected inflammatory bowel disease. The nuclear medicine staff was blinded to
      the patient's specific complaints. RESULTS: The labeled leukocyte scintigraphy
      was positive in 11 of the 15 patients eventually determined to have Crohn's
      disease. Four of the 15 were false negatives. All four of the ulcerative colitis
      patients had normal scans. There were no false-positive scans. The positive
      predictive value was thus 100%, the negative predictive value was 77%, and the
      sensitivity and specificity were 58% and 100% respectively for Crohn's disease.
      CONCLUSIONS: We found radiolabeled leukocyte scintigraphy helpful in prospective,
      blinded assessments of patients with non-stricturizing or non-fistulizing forms
      of Crohn's disease. Scintigraphy may be more justified for reassessments rather
      than in making an initial diagnosis. The scans were of value in Crohn's disease
      but not for ulcerative colitis.

PMID- 14571758
TI  - Gastrointestinal hormones and short-term nutritional schedules in critically ill
      patients.
AB  - BACKGROUND/AIMS: The purpose of the study is to evaluate the gastrointestinal
      hormone response in critically ill patients under different nutritional schedule
      (enteral vs. total parenteral) of short duration. METHODOLOGY: Twenty-one sedated
      and mechanically ventilated patients were nourished with continuous nasogastric
      schedule (Group A, 11 patients), or with total parenteral nutrition (Group B, 10
      patients). Serum concentrations of gastrin, cholecystokinin, vasoactive
      intestinal peptide, neurotensin, and bombesin, were measured on the 2nd, 3rd and
      the 5th day of patients' admission, with radioimmunoassay methods. RESULTS:
      Changes of hormones concentrations were not significant either between the three
      measurements in each group or between the two groups at the same hospitalization
      day. CONCLUSIONS: The short-term parenteral nutrition in critically ill patients
      does not exert a different influence on the serum concentrations of gastrin,
      cholecystokinin, vasoactive intestinal peptide, neurotensin, and bombesin,
      compared to enteral nutrition. This conclusion is of clinical interest since the
      short-term administration of total parenteral nutrition is very often necessary
      during hospitalization in the intensive care unit.

PMID- 14571759
TI  - Novel use of a plastic overtube facilitates intraoperative enteroscopy in Crohn's
      disease.
AB  - Patients with Crohn's disease often need multiple operations. Intraoperative
      endoscopy may obviate the need for repeated operations. A novel use of a plastic
      overtube was applied to facilitate intraoperative endoscopy. The overtube was an
      inexpensive way to prevent contamination; it was applied easily and was found to
      be very helpful. Use of the overtube is suggested for all such endoscopically
      assisted operations.

PMID- 14571760
TI  - Unusual Bochdalek hernia in puerperium.
AB  - The authors present an unusual case of a true left-sided posterolateral
      (Bochdalek) hernia containing stomach, transverse colon and spleen within a
      hernial sac in a 25-year-old female patient. They presume this voluminous
      herniation took place due to a rupture of congenitally preformed hernial ostium
      on account of increased intraabdominal pressure during repeated pregnancy. They
      describe an effective surgical transabdominal laparoscopic treatment.

PMID- 14571762
TI  - Giant hepatic metastasis from gastrointestinal stromal tumor of the rectum 12
      years after surgery.
AB  - Gastrointestinal stromal tumors are non-epithelial neoplasms that arise from the
      gastrointestinal tract. Their variable cytologic atypia makes it difficult to
      predict their prognosis. We report a case of right hepatectomy for a giant
      metastasis detected 12 years after the surgical treatment of a rectal neoplasm,
      histologically demonstrated as a low-grade leiomyosarcoma initially, having
      morphological and immunohistochemical features of low malignancy. Histological
      examination of the hepatic metastases demonstrated that the tumors were composed
      of spindle cells similar to those in the rectal neoplasm. Immunohistochemical
      staining of the hepatic metastases with Ki-67 revealed stronger than the primary
      tumor. In conclusion, although histological and immunohistochemical analyses
      provide useful prognostic information, the prognosis of gastrointestinal stromal
      tumors is difficult to predict. Therefore, a patient with gastrointestinal
      stromal tumor diagnosed as low-grade malignancy requires carefully long-term
      follow-up.

PMID- 14571761
TI  - The importance of follow-up examinations in patients with carcinoid tumor.
AB  - Carcinoid tumors are rare forms of gastrointestinal tumors, although lately they
      have been found with increasing frequency. We report here the combined diagnosis
      of an intestinal metastasized carcinoid tumor. A 67-year-old patient was followed
      up during a nine-year period. In 1990 the patient was diagnosed with carcinoid
      tumor of intestinal origin with multiple liver metastases. Initial treatment
      consisted of partial resection of the intestine and resection of the liver. Since
      multiple liver metastases were found, chemoembolization was also performed. After
      this therapy the patient was free of complaints until 1996. That year the patient
      reported upper abdominal pain with occasional diarrhea. Given his past medical
      history and multiple hepatic metastases proven by three-dimensional
      ultrasonography, combined octreotide and interferon therapy was started following
      octreoscan scintigraphy. During a three-year period the patient was without
      complaints and the tumor marker value decreased to almost normal. In 1998 the
      patient at a regular follow-up visit complained about colic abdominal pain around
      the umbilical region. Abdominal ultrasonography showed a local wall thickening in
      the intestinal region. The computed tomography and selective enterography were
      positive as well. The surgical treatment and histology demonstrated intestinal
      recurrence of the tumor in the ileal region. After the operation we started a
      long-acting sandostatin and interferon treatment. We conclude that an ultrasound
      with a high index of clinical suspicion is a useful test for the diagnosis of
      carcinoid tumor in detection and in follow-up examinations.

PMID- 14571763
TI  - Changes in hepatic parenchymal blood flow with colorectal metastases: increase in
      arterial and decrease in portal blood flow.
AB  - BACKGROUND/AIMS: We investigated the changes in arterial and portal blood flow in
      the non-tumorous liver parenchyma in the presence of colorectal hepatic
      metastases using the H(2)15O dynamic positron emission tomography method.
      METHODOLOGY: Thirty-eight patients were classified into colorectal hepatic
      metastases (MET), hemangioma (HEM), and no liver tumor (NR) groups. We
      quantitatively measured arterial blood flow and portal blood flow in each
      anatomical segment of the non-tumorous liver parenchyma. RESULTS: In the MET, HEM
      and NR groups, the non-tumorous arterial blood flow was 39.89, 32.77 and 28.85
      mL/100 g/minute. Each non-tumorous portal blood flow was 71.61, 100.39 and 94
      mL/100 g/minute. We observed a significant difference in arterial blood flow
      between MET and NR (p = 0.0296), although there was no significant difference in
      total blood flow among three groups. In MET, we discovered a significant
      correlation between tumor and non-tumorous arterial blood flow in the liver
      parenchyma (r = 0.7120, p = 0.0209). Non-tumorous arterial blood flow and PBF
      were 39.07 and 62.74 mL/100 g/minute in the segment with metastases, and 41.95
      and 66.23 mL/100 g/minute without metastases. There were no significant
      differences in any blood flow between those with and without metastasis.
      CONCLUSIONS: The presence of hepatic metastases increased arterial blood flow
      with a compensatory decrease in portal blood flow within the non-tumorous liver
      parenchyma, irrespective of the number, location and size of the metastatic
      lesions.

PMID- 14571765
TI  - Iron depletion and response to interferon in chronic hepatitis C.
AB  - BACKGROUND/AIMS: Chronic viral hepatitis is associated with elevated serum iron
      indexes, and iron accumulation in the liver may contribute to liver injury and
      fibrosis due to hepatitis as well as increased risk of developing hepatocellular
      carcinoma. We studied the effect of iron depletion on the response to subsequent
      interferon therapy in chronic hepatitis C. METHODOLOGY: A population of 83
      patients affected by chronic hepatitis C who had not previously undergone any
      specific therapy and who had laboratory confirmation of iron overload (serum
      ferritin > 400 ng/mL in the males and > 300 ng/mL in the females) was divided
      into two homogeneous groups. The 43 patients in Group A underwent phlebotomy (300
      mL every 10-15 days for an average total of 8 sessions) until their serum
      ferritin levels were < 100 ng/mL. The 40 patients in Group B were treated with
      interferon without prior iron depletion. RESULTS: In Group A, iron depletion
      alone induced a highly significant (p < 0.01) reduction of alanine
      aminotransferase serum values: from 165 U/L (range: 60-370 U/L). Seventy-six
      patients completed therapy and follow-up: a complete and sustained response was
      obtained in 12/39 cases in Group A and in 6/37 cases in group B (p < 0.05).
      CONCLUSIONS: Iron depletion carried out in patients with chronic hepatitis C who
      have elevated serum ferritin values induces a significant reduction in necro
      inflammatory activity (notable decrease in average alanine aminotransferase
      values) and improves their response to subsequent treatment with interferon,
      although it does not modify the viral load.

PMID- 14571764
TI  - Portal thrombosis: late postoperative prevalence in Mansoni's schistosomiasis.
AB  - BACKGROUND/AIMS: Splenectomy with esophagogastric devascularization and distal
      splenorenal anastomosis are used for the treatment of bleeding esophageal varices
      in Mansoni's hepatosplenic schistosomiasis. Portal thrombosis followed by ascitis
      has been observed in the early postoperative phase, but there are no studies
      about the spontaneous and late postoperative prevalence of this vascular
      complication. The aim was to evaluate the spontaneous and late postoperative
      prevalence of total portal vein thrombosis and of ascitis in these patients.
      METHODOLOGY: US-Doppler examination was performed on 168 patients divided in
      three groups: 1) 92 non-operated (preoperative); 2) 62 after splenectomy with
      esophageal devascularization, 3) 14 after distal splenorenal anastomosis. The
      presence of ascitis was sought in all. RESULTS: Group 1 had 5.43% (5/92) of
      spontaneous total portal vein thrombosis, groups 2 and 3, presented 19.35%
      (12/62) and 50.00% (7/14) in the late postoperative follow-up, respectively. The
      Fisher's test showed that group 3 had higher incidence of this vascular occlusive
      complication (p = 0.038). No ascites were found. CONCLUSIONS: Surgical treatment
      of portal hypertension boosts the natural tendency to total portal vein
      thrombosis in this disease. The difference in the occurrence of this vascular
      complication during the late postoperative phase suggests the existence of a
      hemodynamic factor determined by the surgical technique.

PMID- 14571766
TI  - Hyperamylasemia after hepatic resection.
AB  - BACKGROUND/AIMS: Hyperamylasemia often occurs after hepatectomy, but the detailed
      mechanism of this phenomenon remains unclear. The aim of this study was to
      analyze factors that may be associated with the development of hyperamylasemia
      following hepatic resection. METHODOLOGY: The Pringle maneuver was performed in
      12 patients (Pringle group), the hemihepatic vascular occlusion technique in 11
      patients (Hemihepatic group). RESULTS: In the Pringle group, postoperative serum
      amylase levels were elevated significantly in comparison with the preoperative
      levels, but were not elevated in the hemihepatic group. CONCLUSIONS: It is
      suggested that portal congestion by portal triad interruption carries a potential
      risk of serum amylase elevation and pancreatitis after hepatectomy.

PMID- 14571767
TI  - Immune response to hepatitis B vaccine of subjects with isolated antibody to
      hepatitis B core antigen.
AB  - BACKGROUND/AIMS: For subjects with isolated antibody to hepatitis B core antigen,
      vaccination can help discriminate various diagnostic possibilities. The aim of
      this study was to evaluate the clinical significance of isolated antibody to
      hepatitis B core antigen. METHODOLOGY: A total of 1403 hospital personnel were
      screened for hepatitis B surface antigen, antibody to hepatitis B surface antigen
      and antibody to hepatitis B core antigen by radioimmunoassay. Thirty subjects
      were confirmed to have isolated antibody to hepatitis B core antigen, and 278
      subjects lacked all hepatitis B virus markers. Twenty-five of the 30 subjects
      (group I) and 136 of the 278 subjects (group II) were vaccinated by hepatitis B
      vaccine at months 0, 1, 6; followed by checking antibody to hepatitis B surface
      antigen in geometric mean titres at months 1, 2, and 7. RESULTS: The geometric
      mean titres of antibody to hepatitis B surface antigen were higher in group I
      than in group II at month 1 (9.1 +/- 8.6 vs. 3.2 +/- 6.0, p < 0.05), and were
      lower in group I than group II at month 7 (267.2 +/- 17.2 vs. 2315.3 +/- 5.1, p <
      0.05). Furthermore, primary response was higher in group II than group I (73.3%
      vs. 35.7%, p < 0.05), but anamnestic response and non-response were higher in
      group I than group II (50% vs 26.7%, p = 0.116 with a trend; 14.3% vs. 0%, p <
      0.01, respectively). CONCLUSIONS: For subjects with isolated antibody to
      hepatitis B core antigen, a strategy concerning sequential vaccination followed
      by checking antibody to hepatitis B surface antigen might be adopted to avoid two
      extra vaccine dosages and ineffective vaccination.

PMID- 14571768
TI  - Radical surgical treatment of recurrent hepatic hydatidosis.
AB  - BACKGROUND/AIMS: The treatment of relapsing hydatidosis must aim at the reduction
      of both morbidity and mortality rates and the risk of new recurrences.
      METHODOLOGY: Thirty-three patients with recurrence of hepatic ecchinococcosis
      were observed between January 1975 and May 2001. All selected patients received a
      first conservative surgical treatment, and recurrences developed in a period
      ranging from 1 to 46 years from the therapy. All patients with secondary
      hydatidosis were then submitted to radical surgical treatment. Ultrasound
      examinations, the first after 3 months from surgery, were performed to evaluate
      disease recurrence. Intraoperative morbidity and mortality were also evaluated.
      RESULTS: No intraoperative mortality was encountered. Intraoperative and
      postoperative morbidity were 6% and 12% respectively. During follow-up, (mean
      duration 53 months) no recurrences were recorded. CONCLUSIONS: Radical surgical
      approach is the best treatment of recurrent hydatid cysts as it represents a
      valid compromise between the need of a surgical radicality and a low
      intraoperative and postoperative morbidity.

PMID- 14571769
TI  - Intestinal permeability is increased in patients with advanced cirrhosis.
AB  - BACKGROUND/AIMS: The dysfunction of the intestinal barrier is a factor that has
      been related to bacterial translocation from lumen to extra-intestinal sites and
      consequently to the development of spontaneous bacterial peritonitis. The aim of
      this study was to investigate if the alterations of the intestinal barrier in
      cirrhosis are related with the degree of liver failure and associated with other
      clinical complications. METHODOLOGY: Intestinal permeability was assessed by
      means of the lactulose/mannitol test in 79 cirrhotic and 25 controls subjects.
      They received 10 g of lactulose and 5 g of mannitol. Lactulose and mannitol were
      measured in a five-hour urinary volume. RESULTS: Lactulose/mannitol ratio was
      significantly higher in cirrhotic patients than in controls (p = 0.03). This was
      more evident in end-stage cirrhosis. Patients with ascites, or encephalopathy
      showed a statistically significant increase in lactulose/mannitol ratio when
      compared to patients without these complications. CONCLUSIONS: The increased
      intestinal permeability is related to the progression of the liver disease and is
      more relevant with overt clinical complications. This is due to an increased
      absorption of lactulose. However, as liver disease progresses, mannitol
      absorption is progressively reduced, probably due to a reduced surface of
      absorption, and these events are more relevant in patients with overt clinical
      complications.

PMID- 14571770
TI  - The significance of cryoglobulinemia in patients with chronic hepatitis B and C
      virus infection.
AB  - BACKGROUND/AIMS: Mixed cryoglobulinemia is frequently seen in liver disease and
      chronic viral hepatitis. The aim of this study is to determine the prevalence and
      clinical findings of cryoglobulins in patients with chronic hepatitis B and
      chronic hepatitis C. METHODOLOGY: Cryoglobulins were precipitated from serum
      stored for up to 7 days. The precipitates were washed five times at 4 degrees C
      with 0.15 mol/L NaCl and total protein concentration was measured by reading
      absorbance at 280 nm. RESULTS: The prevalence of cryoglobulinemia was higher in
      patients with hepatitis C than in patients with hepatitis B (16.6% and 4.6%
      respectively). Patients with cryoglobulinemia had several symptoms such as
      arthralgia and weakness. CONCLUSIONS: Cryoglobulin-positive chronic hepatitis B
      and C patients should be investigated in terms of cryoglobulinemia symptoms and
      complications.

PMID- 14571771
TI  - Prevalence study of metastases in cirrhotic livers.
AB  - BACKGROUND/AIMS: Metastatic carcinoma is rarely seen in cirrhotic livers. The aim
      of this study is to verify the prevalence of metastases in cirrhotic liver
      comparing cirrhotic patients with a control group. METHODOLOGY: This study is
      based on 7,092 necropsies performed in two big Hospitals of Porto Alegre, Brazil.
      Two thousand seven hundred and three consecutive autopsies were analyzed to study
      the frequency of liver metastases in cirrhotic patients. This material included
      111 cases of liver cirrhosis. A control group was obtained by matching selection
      to compare the prevalence of extrahepatic cancer and hepatic metastases between
      the two groups. RESULTS: Our analysis showed that hepatitis metastases, as well
      as extrahepatic cancer, are less frequently seen in the cirrhotic liver (no cases
      of hepatic metastases and 6 of extrahepatic cancer) compared to the control group
      (10 cases of hepatic metastases and 21 of extrahepatic cancer), this difference
      being statistical significant (p < 0.05). CONCLUSIONS: Our results show that, in
      our sample, hepatic metastases are less common in cirrhosis of the liver than in
      liver without cirrhosis, this result may be due to the fact that patients with
      cirrhosis present less extrahepatic cancers and cirrhotic livers may represent an
      unfavorable site for metastatic growth.

PMID- 14571772
TI  - Gene expression profiles of hepatoma cell line BEL-7402.
AB  - BACKGROUND/AIMS: To investigate the gene expression of cancer related genes in
      hepatoma cell line BEL-7402 through the usage of Atlas Human Cancer Array with
      588 well-characterized human genes related with cancer biology. METHODOLOGY:
      Hybridization of cDNA membrane was performed with 32P-labeled cDNA probes
      synthesized from RNA isolated from Human hepatoma cell line BEL-7402 and non
      cirrhotic normal liver which was liver transplantation donor. Bioinformatics was
      used to analyze the result. The reverse transcription polymerase chain reaction
      of 24 pairs of specimens and northern blot of 4 pairs of specimens were used to
      confirm the expression pattern of some genes identified by Atlas arrays
      hybridization. RESULTS: The differential expression cell cycle/growth regulator
      in hepatoma cell line BEL-7402 showed a stronger tendency toward cell
      proliferation with up-regulation of E2F-3 and TFDP-2. The anti-apoptotic factors
      such as Akt-1 were up-regulated. Whereas the promotive genes of apoptosis were
      down-regulated, such as BAK and caspase-3. Besides this, some genes were up
      regulated, such as Integrin beta 8, DNA-PK, CSPCP, cyclin C etc. A number of
      genes were down-regulated, which included LAR, ABL2, SKY, TDGF1 etc. In general,
      expression of the cancer progression genes were up-regulated, while expression of
      anti-cancer progression genes were down-regulated. The results of reverse
      transcription polymerase chain reaction of 24 pairs of specimens and Northern
      Blot of 4 pairs of specimens were consistent with the expression pattern of some
      genes identified by Atals arrays hybridization. CONCLUSIONS: Investigation of
      gene expression profile of hepatoma cell line BEL-7402 should help to disclose
      the molecular mechanism of the onset, progression and prognosis of hepatocellular
      carcinoma. The quick and high-throughout method of profiling gene expression by
      cDNA array provides us with an overview of key factors that may be involved in
      hepatocellular carcinoma, and may find the clue to the study of hepatocellular
      carcinoma carcinogenesis and molecular targets of diagnosis and therapy.

PMID- 14571773
TI  - Evaluation of interleukin-12-induced interferon-y production in vitro by
      peripheral blood mononuclear cells in patients with chronic liver disease.
AB  - BACKGROUND/AIMS: Interleukin-12 plays an important role in anti-tumor immune
      response by induction of interferon-gamma production by T cells and NK cells, and
      by activation of cytotoxic T cells and NK cells. We evaluated interleukin-12
      induced interferon-gamma production as one of the immunological markers of
      patients with chronic liver diseases. METHODOLOGY: Interleukin-12-induced
      interferon-gamma production was measured in vitro in peripheral blood mononuclear
      cells from 28 hepatocellular carcinoma patients, 10 liver cirrhosis patients, 14
      chronic hepatitis patients and 16 healthy individuals. RESULTS: The
      hepatocellular carcinoma patients exhibited a reduced interleukin-12
      responsiveness for interferon-gamma production compared to the liver cirrhosis
      patients, the chronic hepatitis patients and the healthy individuals. The reduced
      interferon-gamma production seemed to roughly reflect clinical stage in the
      hepatocellular carcinoma patients. The interferon-gamma production correlated
      with neither alpha-fetoprotein nor protein induced by vitamin K absence II.
      CONCLUSIONS: The level of interleukin-12-induced interferon-gamma production by
      peripheral blood mononuclear cells in the patients with hepatocellular carcinoma
      was significantly lower than that in the patients with liver cirrhosis which is
      thought to be a premalignant state. The measurement of interferon-gamma
      production may be useful in evaluating severity of chronic liver disease from an
      immunological point of view.

PMID- 14571774
TI  - Locoregional immunochemotherapy in primary and metastatic liver disease: meta
      analysis and review of literature.
AB  - BACKGROUND/AIMS: Primary and metastatic liver tumors are the most common
      malignancies that resist conventional chemotherapy and radiotherapy. Several
      immunotherapies have been attempted for cancer treatment on the basis of
      stimulating host immune response to tumors and recent development of combined
      targeting locoregional immunochemotherapy reported with promising results.
      However, the efficacy of this therapeutic modality is not yet widely established.
      METHODOLOGY: We reviewed the medical literature for publications dealing with the
      value of locoregional immunochemotherapy in patients with primary or metastatic
      liver tumors. RESULTS: We found that 5 and 7 studies have been controlled and
      inadequately controlled, respectively. Among 131 patients with primary liver
      cancer, 40 were treated with combined locoregional immunochemotherapy, and 20
      with systemic immunochemotherapy, and 71 with systemic chemotherapy served as two
      control groups. Complete or partial response was observed in 32 out of 40 (80%)
      patients who received combined locoregional therapy, and in 10 out of 20 (50%)
      systemic immunochemotherapy controls (P = 0.03). Survival was three times higher
      in the patients who received combined locoregional therapy compared with systemic
      chemotherapy controls (18 vs. 5.6 months). Recurrence of tumor was higher in
      systemic immunochemotherapy controls (P = 0.003). Among 286 patients with
      metastatic liver disease, 180 patients were treated with combined locoregional
      immunochemotherapy and 106 patients with systemic immunochemotherapy. Response
      (complete or partial) was observed in 65 out of 98 (66.3%) patients who received
      combined therapy, and in 4 out of 26 (15.4%) controls (P < = 0.001). Survival was
      two-fold higher in the patients treated with combined therapy (21 vs. 10.5
      months). Tumor recurrence was higher in the systemic immunochemotherapy controls
      (P < = 0.001). CONCLUSIONS: The observational studies indicate a plausible
      therapeutic rationale for the introduction of locoregional immunotherapy in
      patients with primary and metastatic liver disease.

PMID- 14571775
TI  - Evaluation of postoperative nutritional state after hepatectomy for
      hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: In spite of many technical advances in liver surgery, optimal
      nutritional support after hepatectomy has not been established. METHODOLOGY: We
      clarified the actual nutritional state in 16 patients with total parenteral
      nutrition (TPN group), and 16 patients without total parenteral nutrition (PPN
      group), after hepatectomy for hepatocellular carcinoma without biliary tract
      reconstruction, in terms of preoperative clinical data, intraoperative indexes,
      postoperative management and complications, liver function data, nutritional
      state, and changes in metabolic parameters. RESULTS: There were no significant
      differences in any occurrences of postoperative complications, liver function
      data, or nutritional parameters between the two groups. On the other hand, the
      TPN group needed more doses of insulin than the PPN group. The beginning of each
      water and food intake was earlier in the PPN group than in the TPN group. The
      blood glucose level was higher in the TPN group than in the PPN group. The serum
      sodium and chloride levels were lower, but the serum potassium level was higher,
      in the TPN group compared to the PPN group. Thus, problems such as hyperglycemia
      and serum electrolyte abnormalities were more conspicuous in the TPN group than
      in the PPN group. CONCLUSIONS: In the actual clinical care after hepatectomy for
      hepatocellular carcinoma without biliary tract reconstruction, in which oral
      feeding is started early, total parenteral nutrition is considered unnecessary.

PMID- 14571776
TI  - Incidence of bile leakage after three types of hepatic parenchymal transection.
AB  - BACKGROUND/AIMS: Bile leakage is a major morbidity associated with hepatectomies.
      No study has been performed correlating various methods of liver transection to
      incidences of bile leakage. METHODOLOGY: The 89 patients with hepatocellular
      carcinoma who received hepatectomy were classified into 3 groups according to the
      specific method of liver resection: cavitron ultrasonic surgical aspirator
      (CUSA), microwave tissue coagulation (MTC), and clamp crushing (CC). Comparisons
      in the incidences of bile leakage and length of hospital stay were made among
      these groups. RESULTS: The CC group showed a significantly lower incidence of
      bile leakage than the MTC group (3% vs. 27%, P = 0.03). In the median
      postoperative hospitalization length, the CC group demonstrated a significantly
      shorter period than that in the MTC group (25 vs. 35 days, P = 0.03). No
      significant differences were found for operation time, amount of blood loss or
      resected tumor size in the 3 groups. CONCLUSIONS: In view of the incidence of
      bile leakage, CC is a favorable technique for hepatectomy.

PMID- 14571777
TI  - Platelet-derived endothelial cell growth factor (PD-ECGF) is up-regulated in
      human hepatocellular carcinoma (HCC) and the corresponding hepatitis liver.
AB  - BACKGROUND/AIMS: Platelet-derived endothelial cell growth factor (PD-ECGF) is one
      of the angiogenic factors. The aim of this study was to examine the PD-ECGF
      concentrations in hepatocellular carcinoma, background liver, and normal liver
      tissues, and to elucidate their significance on clinicopathological outcomes.
      METHODOLOGY: The concentration of PD-ECGF in the tissue extract was determined by
      enzyme-linked immunosorbent assay. RESULTS: PD-ECGF concentrations were
      significantly higher in hepatocellular carcinoma and background liver tissues
      compared with normal control liver (p = 0.003, p = 0.001, respectively). PD-ECGF
      concentrations in hepatocellular carcinoma tissues were positively correlated
      with intratumoral arteriole densities (r = 0.667, p = 0.009), and were higher in
      less differentiated carcinomas (p = 0.039). However, tumor PD-ECGF concentration
      did not affect the patients' disease-free survival rates. Those in the background
      liver tissues were positively correlated with histological activity index scores
      (r = 0.650, p = 0.001) and serum alanine aminotransferase levels (r = 0.0452, p =
      0.035). CONCLUSIONS: PD-ECGF is up-regulated in hepatocellular carcinoma and the
      corresponding hepatitis liver. The PD-ECGF concentrations in hepatocellular
      carcinoma correlated positively with microvessel density, lower differentiation,
      yet not with patients' prognosis. The concentrations of PD-ECGF in the
      corresponding hepatitis liver correlated positively with the degree of active
      hepatitis.

PMID- 14571778
TI  - Portal vein thrombosis in cirrhotics: related with anticardiolipin antibodies?
AB  - BACKGROUND/AIMS: To evaluate the relationship of antiphospholipid antibodies and
      portal vein thrombosis in cirrhotics. METHODOLOGY: 22 cirrhotics without portal
      vein thrombosis (Group I), 18 with portal vein thrombosis (Group II) and 20
      healthy controls (Group III) were enrolled. Anticardiolipin IgG and IgM antibody
      concentrations were measured by ELISA and lupus anticoagulant by clotting. Groups
      were compared according to sex, age, etiology of cirrhosis, prior intraabdominal
      surgery, Child groups, anticardiolipin IgG, IgM and lupus anticoagulant. Then for
      all the 40 cirrhotics (Group IV) correlation was tested between anticardiolipin
      IgM, IgG, lupus anticoagulant and Child groups, etiology of cirrhosis, sex and
      prior surgery. RESULTS: In Group I, anticardiolipin IgG concentration was 15.3
      (15.9) GPL)/mL and IgM was 8.6 (6.5) MPL/mL. In 6 (27.27%) anticardiolipin IgG,
      in 6 (27.27%) IgM and in 2 (9.09%) both were high. Lupus anticoagulant was
      positive in 7 (31.81%). In Group II anticardiolipin IgG concentration was 26.3
      (14.7) GPL/mL and IgM was 15.1 (7.2) MPL/mL. In 10 (55.55%) anticardiolipin IgG,
      in 13 (72.22%) IgM and in 9 (50%) both were high. Lupus anticoagulant was
      positive in 5 (27.77%). In Group III lupus anticoagulant was positive in 1
      (0.5%). Anticardiolipin IgG was 10.3 (5.9) GPL/mL, IgM 5 (3.6) MPL/mL
      anticardiolipin IgM level was high in 1 (0.5%). Group I and II were similar with
      respect to lupus anticoagulant, Child groups, prior intraabdominal surgery and
      etiology of cirrhosis. For anticardiolipin IgG and IgM there was a significant
      difference between Group I and II, I and III and II and III. In Group IV there
      was no correlation between prior abdominal surgery, Child groups, sex, etiology
      and anticardiolipin IgG, IgM or lupus anticoagulant. CONCLUSIONS: Anticardiolipin
      antibody concentrations were significantly higher in cirrhotics with portal vein
      thrombosis. Thus anticardiolipin antibodies may play a role in the development of
      portal vein thrombosis in cirrhosis.

PMID- 14571779
TI  - Clinical characteristics and prognostic indicators of drug-induced fulminant
      hepatic failure.
AB  - BACKGROUND/AIMS: In most cases of drug-induced liver injury, it is difficult to
      diagnose whether these cases would progress to fulminant hepatic failure. We
      investigated the characteristics of non-viral and suspiciously drug-induced
      fulminant hepatic failure by comparing clinical data between cases that
      progressed and those that did not progress to fulminant hepatic failure.
      METHODOLOGY: Ninety-five cases of suspicious drug-induced liver injury including
      22 cases that had been treated at our hospital, and subsequently progressed to
      fulminant hepatic failure were involved in this study. We investigated the
      characteristics of drug-induced fulminant hepatic failure by a comparison of non
      fulminant and fulminant cases, and simultaneously of survivors and fatal cases in
      the group of fulminant cases. RESULTS: Many of the clinical variables were
      significantly deteriorated in fulminant cases. The latent period, which means the
      duration of drug administration, correlated with the severity of drug-induced
      liver injury including fulminant hepatic failure. Suspicious cases of drug
      induced liver injury where the bilirubin level at the time of definite diagnosis
      stayed over 13 mg/dL for more than one month were likely to progress to fulminant
      hepatic failure. CONCLUSIONS: Our results suggest that the latent period and the
      peak level of total bilirubin would be prognostic factors for the severity of
      drug-induced fulminant hepatic failure. Early preparation of liver
      transplantation should be recommended by referring these characteristics.

PMID- 14571780
TI  - Portal hemodynamics in primary biliary cirrhosis as evaluated by per-rectal
      portal scintigraphy with Tc-99m pertechnetate.
AB  - BACKGROUND/AIMS: Portal circulation can be evaluated in a relatively noninvasive
      manner by per-rectal portal scintigraphy. We used this method to evaluate portal
      hemodynamics in patients with primary biliary cirrhosis and idiopathic portal
      hypertension. We did the procedures simultaneously in some patients to examine
      the relation between portal circulation and hepatic functional reserve in these
      diseases. METHODOLOGY: Per-rectal portal scintigraphy with Tc-99m pertechnetate
      was done in 17 healthy subjects, 154 patients with chronic hepatitis, 447
      patients with cirrhosis, 40 patients with primary biliary cirrhosis, and 20
      patients with idiopathic portal hypertension. Eighty-three patients (14 with
      hepatitis, 48 with cirrhosis, 16 with primary biliary cirrhosis, and 5 with
      idiopathic portal hypertension) also underwent scintigraphy with Tc-99m
      galactosyl human serum albumin with 2 weeks. A solution containing Tc-99m
      pertechnetate was instilled into the rectum, and serial scintigrams were taken
      while radioactivity curves for the liver and heart were recorded sequentially.
      The per-rectal portal shunt index was calculated from the curves. A receptor
      index was calculated by dividing the radioactivity of the liver region of
      interest by that of the liver-plus-heart region of interest 15 min after the
      injection of Tc-99m galactosyl human serum albumin. The index of blood clearance
      was calculated by dividing the radioactivity of the heart region of interest at
      15 min by that of the heart region of interest at 3 min. RESULTS: The shunt index
      was higher for more severe disorders, increasing in the order of chronic
      hepatitis, cirrhosis without varices, and cirrhosis with varices. The shunt
      indices in patients with primary biliary cirrhosis and idiopathic portal
      hypertension were higher than that in patients with chronic hepatitis. In terms
      of receptor index, the standard residuals were more than 0 in 10 of 16 patients
      with primary biliary cirrhosis and 4 of 5 patients with idiopathic portal
      hypertension. In terms of index of blood clearance, the standard residuals were
      more than 0 in 10 of 16 patients with primary biliary cirrhosis and 4 of 5
      patients with idiopathic portal hypertension CONCLUSIONS: Abnormalities of portal
      hemodynamics in patients with primary biliary cirrhosis or idiopathic portal
      hypertension occur while hepatic functional reserve is still satisfactory as
      compared with patients who have chronic hepatitis or cirrhosis.

PMID- 14571781
TI  - Is intraoperative ultrasonography during partial hepatectomy still necessary in
      the age of magnetic resonance imaging?
AB  - BACKGROUND/AIMS: The aim of our study was to determine if intraoperative
      ultrasonography is still necessary in the time of magnetic resonance imaging.
      METHODOLOGY: Our prospective study comprised 122 patients (82% with malignant
      tumors) undergoing partial hepatectomy with preoperative magnetic resonance
      imaging, done at the same institution using a standardized liver protocol as well
      as intraoperative ultrasonography performed in a systematic fashion. RESULTS:
      Seventeen additional malignant lesions in 16/122 patients (13.1%) were found
      intraoperatively [7 visible, 2 palpable, 8 (6.6%) diagnosed by intraoperative
      ultrasonography only; mean size: 1.5 cm; left:right lobe = 11:6]. This caused a
      change in surgical strategy in 14 patients (11.5%), including 6 patients (4.9%)
      with lesions seen on intraoperative ultrasonography only. The average total
      number of lesions in those patients was 3.4. Ten lesions (7 benign, 3 malignant)
      described on magnetic resonance imaging were not found on intraoperative
      ultrasonography, but no unnecessary operations resulted from this. In one patient
      additional micrometastases seen neither on magnetic resonance imaging nor on
      intraoperative ultrasonography were found histologically. CONCLUSIONS:
      Intraoperative ultrasonography is still worthwhile as it remains unsurpassed in
      the ultimate determination of the number of lesions, tumor extension and
      anatomical resolution. However, in the course of time its benefits may decrease
      further due to ongoing improvement of preoperative imaging.

PMID- 14571782
TI  - Short and long-term effects of bacterial translocation due to obstructive
      jaundice on liver damage.
AB  - BACKGROUND/AIMS: The present study was conducted to determine if obstructive
      jaundice promotes bacterial translocation and to evaluate the changes in hepatic
      histopathology in patients with benign biliary obstruction. METHODOLOGY: Between
      January 1996 and January 1998, 19 patients treated for benign biliary obstruction
      were studied. Fourteen patients with symptomatic cholelithiasis were taken as the
      control group. Patient characteristics, preoperative and post-operative
      laboratory tests with an interval of 7 days were recorded. In all patients, bile
      and mesenteric lymph nodes samples were taken for bacterial growth and
      histopathologic changes were studied on the liver excised during surgery.
      RESULTS: In the control group, bacterial growth was observed in the bile and
      mesenteric lymph nodes cultures in one (7.1%) and two patients (14.3%),
      respectively. In the study group, 8 patients (42%) had positive bile cultures and
      12 patients (63.2%) had positive mesenteric lymph nodes cultures, respectively.
      Histopathologic examination of the liver revealed significant increase in the
      rate of periductal and portal fibrosis in the jaundiced patients, compared with
      control group (p < 0.001). Postoperative complications in the study group were
      wound infection (3 cases), renal failure (2 cases), ARDS (1 cases) and
      intraabdominal abscess (1 cases). In the control group, one patient had wound
      infection and one had atelectasis. Two patients with jaundice died of multiple
      organ failure and respiratory failure. In long-term follow-up (mean 17 months),
      when sclerosing cholangitis and secondary biliary cirrhosis developed in one
      patient each in the study group, no long-term complication occurred in the
      control group. CONCLUSIONS: Our clinical results demonstrate that extrahepatic
      biliary obstruction promotes bacterial translocation and this process is an
      important cause of morbidity and mortality in patients with jaundice. Also,
      obstructive jaundice subsequently leads to significant functional and
      morphological damage in the liver.

PMID- 14571783
TI  - Percutaneous microwave coagulation therapy for superficial hepatocellular
      carcinoma on the surface of the liver.
AB  - BACKGROUND/AIMS: This study was performed to evaluate the efficacy and safety of
      percutaneous microwave coagulation therapy for superficial hepatocellular
      carcinoma located on the surface of the liver. METHODOLOGY: Among 58 cirrhosis
      patients with 71 hepatocellular carcinomas measuring < or = 20 mm in greatest
      dimension, 18 patients had a solitary superficial lesion located on the liver
      surface (superficial hepatocellular carcinoma group) and the other 40 patients
      had 53 lesions that were not in contact with the liver surface (non-superficial
      hepatocellular carcinoma group). All patients were treated by percutaneous
      microwave coagulation therapy alone and the response was assessed by using
      contrast-enhanced CT. The survival, tumor recurrence, and adverse effects were
      compared between the superficial and non-superficial hepatocellular carcinoma
      groups. RESULTS: The 4-year survival rates of the superficial hepatocellular
      carcinoma group (64.2%) and the non-superficial hepatocellular carcinoma group
      (58.9%) were not significantly different, and neither were the 4-year local
      recurrence rates (27.1% vs. 29.8%). Although there was a significantly higher
      incidence of severe pain during microwave irradiation in the superficial
      hepatocellular carcinoma group (23/47) when compared with the non-superficial
      hepatocellular carcinoma group (25/148), there were no differences between them
      in the incidence of fever or the changes in liver function after treatment. There
      were no serious adverse effects, such as hemorrhage or tumor cell seeding, in
      either group. CONCLUSIONS: Percutaneous microwave coagulation therapy can be
      performed safely, even in patients with superficial hepatocellular carcinoma and
      cirrhosis, so this method is effective for treating hepatic neoplasms regardless
      of the tumor location.

PMID- 14571784
TI  - Operative risk by the lidocaine test (MEGX) in resected patients for HCC on
      cirrhosis.
AB  - BACKGROUND/AIMS: The purpose of this study was to evaluate the clinical
      usefulness of the preoperative lidocaine test (MEGX) in cirrhotic patients who
      were candidates for curative liver resection for hepatocellular carcinoma.
      METHODOLOGY: To evaluate whether MEGX was related to postoperative complications,
      a retrospective analysis was carried out on 51 patients, in whom a preoperative
      lidocaine test was available. They were divided into two groups according to a
      MEGX value less (22 patients, group A) or more (29 patients, group B) than 25
      ng/mL. RESULTS: The two groups of patients were comparable for the preoperative
      clinical parameters and the surgical procedures. Patients in group A had a
      significantly higher rate of postoperative complications (73% vs. 28%, p < 0.005)
      and a tendency to a longer hospital stay, compared to patients in group B.
      CONCLUSIONS: The lidocaine value is an effective index of hepatic function. A
      preoperative MEGX value lower than 25 ng/dL in cirrhotic patients was related to
      a significantly higher risk of liver insufficiency and postoperative
      complications after hepatic resection.

PMID- 14571786
TI  - Analysis of the prognostic factors for liver metastasis of gastric cancer after
      hepatic resection: a multi-institutional study of the indications for resection.
AB  - BACKGROUND/AIMS: The number of reports of hepatic resection for metastatic
      gastric cancer is very small. The outcome and indications of hepatic resection
      for metastatic gastric cancer remains unknown. METHODOLOGY: A multi-institutional
      study was made. Thirty-six patients who underwent a hepatic resection for liver
      metastasis of gastric cancer with no residual tumor were included in this study.
      The clinicopathological factors were examined as prognostic factors by
      multivariate analyses. Thirty patients had recurrence and the recurrence pattern
      and risk factors for extrahepatic recurrence was examined. RESULTS: The overall
      survival rate was 64% at 1 year, 43% at 2 years, 26% at 3 years 26% at 5 years,
      and 26% at 10 years after hepatectomy. Multivariate analysis showed that
      lymphatic invasion, venous invasion of cancer cells of primary gastric cancer and
      the number of the liver metastasis (> 3) were independent poor prognostic factors
      after hepatic resection. The most common recurrence pattern was intrahepatic
      recurrence in 22 patients (73%). The risk factors for extrahepatic recurrence was
      serosal invasion, lymph node metastasis of primary gastric cancer, stage, and
      curability of operation. CONCLUSIONS: Hepatic resection for liver metastasis
      should be attempted in case primary gastric cancer has neither lymphatic invasion
      nor venous invasion. The most common recurrent site was the liver. In patients
      with advanced gastric cancer, having neither serosal invasion nor lymph node
      metastasis, who underwent a less curative operation, the intra-hepatic recurrence
      would be expected. Thus, aggressive adjuvant chemotherapy through the hepatic
      artery may improve the survival after hepatectomy in these patients.

PMID- 14571785
TI  - Long-term follow-up of patients with liver cirrhosis after endoscopic ethanol
      injection sclerotherapy for esophageal varices.
AB  - BACKGROUND/AIMS: Esophageal variceal hemorrhage is a severe complication of liver
      cirrhosis, and therapy for acute bleeding and prevention of hemorrhage are
      important. In this study, we evaluated the long-term cumulative survival rate of
      patients with esophageal varices after treatment with endoscopic ethanol
      injection sclerotherapy (EIS group) or pharmacological therapy (non-EIS group).
      METHODOLOGY: All 110 patients were treated for their esophageal varices and their
      prognosis and complications were analyzed during the follow-up period. RESULTS:
      The cumulative survival rate in the primary preventive EIS group was superior to
      that in the non-EIS group. The preventive EIS group had greater long-term
      survival rate than those treated on an emergency group. With respect to emergency
      therapy, the EIS group had better survival rates than the non-EIS group during
      the two-year follow-up period after esophageal variceal therapy. CONCLUSIONS: We
      conclude that primary preventive EIS is an effective therapy for survival of
      patients with esophageal varices over a long-term period.

PMID- 14571787
TI  - Characteristics of hepatocellular carcinoma in hemodialysis patients in hepatitis
      B endemic area.
AB  - BACKGROUND/AIMS: Hepatocellular carcinoma is one of the most common malignancies
      in Taiwan, a hepatitis B endemic area. In this study, we aimed to evaluate the
      characteristics of hepatocellular carcinoma in patients receiving hemodialysis,
      as this patient group is at high risk for malignancy. METHODOLOGY: From October
      1991 to September 1997, thirteen patients receiving hemodialysis and diagnosed
      with hepatocellular carcinoma were enrolled in this retrospective study.
      Patients' clinical course, laboratory data, image study and treatment were
      evaluated. RESULTS: Among these 13 patients, hepatitis B virus related in 6 and
      hepatitis C virus related in 7. There was no statistical significance in serum
      levels of asparate aminotransferase, alanine aminotransferase, bilirubin and
      alpha-fetoprotein between hepatitis B virus and hepatitis C virus related
      hepatocellular carcinoma. Hepatitis B virus related hepatocellular carcinoma had
      a shorter mean dialysis period (29.67 +/- 22.18 vs. 87.86 +/- 79.90 months, P =
      0.25) and mean duration from beginning hemodialysis to diagnosis of
      hepatocellular carcinoma (17.16 +/- 26.94 vs. 76.08 +/- 65.69 months, P = 0.05),
      but there was no statistical significance. In the area of treatment, the survival
      curves of the treatment (hepatic resection and/or transcatheter arterial
      chemoembolization) group and supportive group were compared by log-rank test and
      there was no statistical significance for these two groups (P = 0.69).
      CONCLUSIONS: Both hepatitis B virus and hepatitis C virus are equally important
      for hepatocellular carcinoma in hemodialysis patients in hepatitis B endemic
      Taiwan. The acquisition of hepatitis B virus or hepatitis C virus might be not
      related to hemodialysis. Periodic screening with ultrasonography and serum alpha
      fetoprotein is necessary among hemodialysis patients with evidence of hepatitis B
      virus or hepatitis C virus infection.

PMID- 14571788
TI  - Serum levels of interleukin-10, interleukin-12 and soluble interleukin-2 receptor
      in chronic liver disease type C.
AB  - BACKGROUND/AIMS: It is still unclear whether and how Th1/Th2 type cytokines are
      involved in the progression of chronic liver disease type C. We therefore
      examined serum levels of IL-10, IL-12 and sIL-2R (soluble IL-2 receptor) in
      association with clinical parameters in chronic liver disease type C, whereas IL
      12 and sIL-2R represent Th1 cytokine and IL-10 does Th2 cytokine, respectively.
      METHODOLOGY: Serum levels of IL-10, IL-12 and sIL-2R were measured in 110
      patients, including 36 with chronic hepatitis, 24 with liver cirrhosis and 50
      with hepatocellular carcinoma in comparison with 19 normal individuals, by an
      enzyme-linked immunosorbent assay. In 9 chronic hepatitis patients, serum levels
      of these cytokines were measured before and after interferon therapy. In 28 with
      hepatocellular carcinoma, they were also measured before and after transcatheter
      arterial embolization. RESULTS: Serum levels of IL-10 in chronic hepatitis, liver
      cirrhosis and hepatocellular carcinoma were 3.9 +/- 1.8 pg/mL, 5.7 +/- 6.4 pg/mL
      and 5.6 +/- 8.9 pg/mL, respectively. IL-10 level was significantly correlated
      with level of y-globulin. Serum levels of IL-12 in chronic hepatitis, liver
      cirrhosis and hepatocellular carcinoma were 347.4 +/- 150.3 pg/mL, 365.2 +/-
      130.7 pg/mL and 399.4 +/- 258.2 pg/mL. sIL-2R levels in chronic hepatitis, liver
      cirrhosis and hepatocellular carcinoma were 614.6 +/- 223.5 U/mL, 878.7 +/- 330.5
      U/mL and 1037.9 +/- 412.0 U/mL. Serum levels of IL-12 and sIL-2R were
      significantly elevated on day 7 after interferon therapy compared to day 0 (p <
      0.05 and p < 0.001, respectively), while no significant difference was seen in IL
      10. Serum level of IL-10 was significantly elevated on day 3, and that of sIL-2R
      was elevated on day 3 and 7 after transcatheter arterial embolization, while that
      of IL-12 was decreased on day 3 and 7. CONCLUSIONS: The results of the present
      study suggest that Th1/Th2 type cytokines are changed in association with
      progression of chronic liver disease type C and in response to therapy.

PMID- 14571789
TI  - Combination of interferon alfa-2a and amantadine does not improve the efficacy of
      interferon therapy in patients with chronic hepatitis C.
AB  - BACKGROUND/AIMS: A recent pilot study suggested that 18% of patients with
      hepatitis C viral infection achieved a sustained response to a 6-month course of
      200 mg of oral amantadine alone with disappearance of serum hepatitis C virus
      ribonucleic acid. We prospectively studied 30 naive patients with chronic
      hepatitis C viral infection for the possible role of amantadine in improving the
      efficiency of interferon for the treatment of chronic hepatitis C. METHODOLOGY:
      Patients were assigned into two groups on a double-blind and randomized
      controlled basis. Placebo group received 4.5 MU of interferon alfa-2a thrice
      weekly and oral placebo daily for 24 weeks. Amantadine group received a
      combination of the interferon and 200 mg of oral amantadine daily for 24 weeks.
      Patients were observed and tested for blood chemistry every week for the initial
      4 weeks and every 2 weeks thereafter during the treatment until 24 weeks. After
      the end of treatment, patients were followed up at 4-week intervals for an
      additional 12 months. RESULTS: At the end of treatment, 5 (33.3%) patients
      responded to the combination therapy, and 7 (46.7%) patients responded to
      interferon therapy alone. Twelve months after cessation of the treatment, 3
      (21.4%) patients had a sustained complete response to the combination therapy,
      and 3 (20.0%) patients had a sustained complete response to interferon alone (P =
      0.64). CONCLUSION: Amantadine does not increase the efficacy of interferon in the
      treatment of chronic hepatitis C.

PMID- 14571790
TI  - Loss of heterozygosity at D14S62 and D14S51 detected by a simple and non
      radioactive method in plasma DNA is a potential marker of metastasis and
      recurrence after curative hepatic resection in hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: Recurrence and metastasis in hepatocellular carcinoma remains a
      major challenge to further improve survival. High frequency of loss of
      heterozygosity at D14S62 and D14S51 in tumor tissue has been shown to be closely
      related to metastasis and recurrence in breast cancer. But, loss of
      heterozygosity on 14q in plasma and tumor tissue DNA of hepatocellular carcinoma
      patients has not been investigated. To establish a way to predict metastasis and
      recurrence after curative hepatic resection, we analyzed loss of heterozygosity
      on 14 q in plasma and tumor tissue DNA of hepatocellular carcinoma patients with
      curative resection. METHODOLOGY: We used a simple, rapid and non-radioactive
      method to analyze loss of heterozygosity at D14S62 and D14S51 in paired plasma,
      lymphocyte and tumor tissue DNA of 85 hepatocellular carcinoma patients with
      curative resection. RESULTS: From 79 cases informative for D14S62 and 78 cases
      informative for D14S51 of 85 hepatocellular carcinoma tissue DNA, loss of
      heterozygosity at D14S62 and D14S51 was present in 45 (57.0%) and 41 (52.6%)
      cases respectively. And in 96.0% of the tissues which showed loss of
      heterozygosity we were able to detect loss of heterozygosity in their matched
      plasma. In matched 85 cases of hepatocellular carcinoma plasma DNA, we detected
      loss of heterozygosity at D14S62 in 55.7% and at D14S51 in 50.0% of the
      respective informative DNA samples. The loss of heterozygosity patterns of plasma
      DNA were almost identical to their corresponding tumor tissues. A comparison of
      these genetic changes with clinicopathological data of these checked
      hepatocellular carcinoma patients showed that loss of heterozygosity at D14S62
      and D14S51 was adversely correlated significantly with the presence of tumor
      size, with 35.4% at both the D14S62 and D14S51 locus in the HTMR (high-tendency
      to metastasis and recurrence) group compared with 72.9% and 59.4% in the LTMR
      (low-tendency to metastasis and recurrence) group at D14S62 and D14S51,
      respectively (P = 0.001 and P = 0.027, respectively). CONCLUSION: Our results
      suggest that loss of heterozygosity at D14S62 and D14S51 plays an important role
      in the metastasis and recurrence of hepatocellular carcinoma patients following
      curative resection. Loss of heterozygosity at D14S62 and D14S51 in the plasma DNA
      of hepatocellular carcinoma patients detected by a simple and non-radioactive
      method has great potentials to be clinically used to predicate metastasis and
      recurrence after curative hepatic resection.

PMID- 14571791
TI  - Low-dose cisplatin plus oral tegafur and uracil for the treatment of lung
      metastases of hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: An effective treatment for unresectable multiple lung metastases
      of hepatocellular carcinoma have never been established. METHODOLOGY: Six
      patients received the chemotherapy described herein as an initial treatment for
      lung metastases of hepatocellular carcinoma. Low-dose cisplatin infusion plus
      oral tegafur and uracil administration combination therapy essentially consisted
      of cisplatin (10 mg/day over 1 hour) infused on days 1-5 every week and oral
      tegafur and uracil (300 mg/day) administrated every day. This treatment was
      repeated weekly for essentially 4 consecutive weeks. RESULTS: Complete response
      was observed in no cases and partial response in 3 cases, while no change was
      observed in 4 cases and progressive disease in one case. An overall response rate
      was 50%. The serum alpha-fetoprotein and des-Y-carboxyprothrombin were reduced in
      most of the patients. Leukopenia of grade 2 was observed in only 1 (17%) patient.
      Thrombocytopenia of grade 2 was observed in 2 (33%) patients. Nausea (up to Grade
      2) was occurring in 4 (67%) patients. Three patients with no other distant
      metastasis survive more than two years after lung metastasis, and the quality of
      life of these patients are well preserved. CONCLUSIONS: Low-dose cisplatin
      infusion combined with oral tegafur and uracil administration for the treatment
      of lung metastases of hepatocellular carcinoma may be an effective regimen with a
      high response rate and acceptable toxicities, although a larger study will be
      necessary to confirm the efficacy.

PMID- 14571792
TI  - Blockade of Kupffer cells by gadolinium chloride reduces lipid peroxidation and
      protects liver from ischemia/reperfusion injury.
AB  - BACKGROUND/AIMS: The implication of lipid peroxidation in the inhibitory effect
      of GdCl3 (gadolinium chloride) on Kupffer cells activation has not been
      extensively investigated. The aim of this study was to examine the effect of
      GdCl3 inhibition of Kupffer cells activation on lipid peroxidation after severe
      total hepatic ischemia/reperfusion. METHODOLOGY: Male Wistar rats (n = 40) were
      randomly divided into a sham-operation group, a control ischemia/reperfusion
      group, and two ischemia/reperfusion groups pretreated with GdCl3 (10 mg and 20
      mg/kg bw intravenously, 48 and 24 h prior to operation). Following 60 min of
      total hepatic ischemia and 120 min of reperfusion, the rats were sacrificed, and
      liver samples were taken for determination of malondialdehyde and light
      microscopy examination. Blood samples were also taken for assay of aspartate and
      alanine transaminase. Additional animals (n = 60) were followed up for a 7-day
      survival rate determination. RESULTS: Ischemia/reperfusion decreased the survival
      rate to 13.3%, increased (p < 0.001) the levels of aspartate and alanine
      transaminase in serum to 2387 +/- 75 and 2157 +/- 87 IU/L, respectively, and
      increased (p < 0.001) malondialdehyde levels in liver to 1.609 +/- 0.096 nmoles/g
      compared with 1.164 +/- 0.060 in the sham operation group. Pretreatment with
      GdCl3 increased the survival rate to 60%, and decreased (p < 0.001) the levels of
      aspartate transaminase in serum to 1549 +/- 66 and 1496 +/- 55 IU/L, the levels
      of alanine transaminase in serum to 1302 +/- 48 and 1305 +/- 63 IU/L, and the
      levels of malondialdehyde in liver to 1.132 +/- 0.034 and 1.149 +/- 0.57 nmoles/g
      for the lower and the higher doses of GdCl3, respectively. Histological
      examination showed protection of liver parenchyma in the animals treated with
      GdCl3. CONCLUSIONS: Experimental data suggest that GdCl3 inhibition of Kupffer
      cells activation protects liver from ischemia/reperfusion injury by a mechanism
      that reduces lipid peroxidation.

PMID- 14571793
TI  - Serum 7alpha-hydroxycholesterol levels during liver regeneration after
      hepatectomy in humans.
AB  - BACKGROUND/AIMS: Changes in bile acid synthesis during liver regeneration after
      hepatectomy is little known in humans. Since it has been reported that the serum
      7 alpha-hydroxycholesterol levels reflect the hepatic bile acid synthesis and
      that the determination of bile acid synthesis is useful to assess the liver
      regeneration rate, we determined the serum 7 alpha-hydroxycholesterol level
      during liver regeneration after hepatectomy in clinical patients. METHODOLOGY:
      The serum 7 alpha-hydroxycholesterol levels were determined by gas-liquid
      chromatography-mass spectrometry-selected ion monitoring method before and on
      days 1, 3, 5, 7, 14 and 21 after hepatectomy in twenty consecutive patients.
      RESULTS: The 7 alpha-hydroxycholesterol levels became lower between days 1 and 7,
      were increased on day 14, and then decreased on day 21 after hepatectomy. The
      patients with preoperative external biliary drainage showed a higher serum 7
      alpha-hydroxycholesterol level than those without biliary drainage before
      hepatectomy. The former showed lower serum 7 alpha-hydroxycholesterol levels than
      the latter throughout the 21 days after hepatectomy. In patients whose liver
      resection rate was more than 50%, the serum 7 alpha-hydroxycholesterol levels
      were kept lower until 21 days after hepatectomy compared with those whose liver
      was excised less than 50%. CONCLUSIONS: It is concluded that the patients who had
      preoperative biliary drainage or major hepatic resection seem to have less
      hepatic reserve capacity for bile acid synthesis after hepatectomy.

PMID- 14571794
TI  - A new chemotherapeutic regimen for advanced unresectable hepatocellular
      carcinoma.
AB  - BACKGROUND/AIMS: The aim of this study was to evaluate the efficacy and toxicity
      of a novel chemotherapeutic regimen for advanced unresectable hepatocellular
      carcinoma. METHODOLOGY: Seventeen patients with unresectable hepatocellular
      carcinoma were treated by arterial infusion once a week of low-dose cisplatin (12
      mg/m2) and doxorubicin (6 mg/m2) via a subcutaneously implanted injection port
      and by daily oral administration of 300 mg/day of UFT comprising 5-fluorouracil
      prodrug tegafur (FT) and uracil (U) at a ratio of 1:4. RESULTS: The median number
      of chemotherapy courses was 13 (range, 5-33). All patients were evaluated for
      response, toxicity, and survival. As assessed by conventional imaging criteria,
      there were 3 (17.6%) complete responses with disappearance of the primary tumor,
      tumor thrombosis of the portal vein and metastatic para-aortic lymph node
      swelling. In addition, there were 4 (23.5%) partial responses. Among 11 patients
      who had initially high alpha-fetoprotein levels (> 200 ng/mL), 5 (45%) had a >
      50% drop after therapy. The overall tumor response rate (complete response +
      partial response) was 41% and the median survival was 7.1 (range; 4.2-25.1)
      months. As for toxicity, there was 1 treatment-related death due to septicemia
      caused by catheter-related infection. Myelosuppression and renal toxicity was
      relatively mild and transient. CONCLUSIONS: These results suggest that our low
      dose chemotherapeutic regimen may be useful for the treatment of advanced
      unresectable hepatocellular carcinoma without worsening the quality of life of
      the patient.

PMID- 14571795
TI  - Clinical significance and prediction factors of gastric varices in patients with
      hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: Hepatocellular carcinoma is part of the natural history of liver
      cirrhosis. Gastrointestinal bleeding and hepatic failure are the leading causes
      of death in hepatocellular carcinoma patients. With gastrointestinal bleeding,
      variceal bleeding is the most prominent, and most variceal bleeding is of
      esophageal origin. Gastric varices bleeding is often a massive and severe
      bleeding episode. The role of gastric varices among patients with hepatocellular
      carcinoma remains to be clarified. In this study, we aimed to evaluate the
      prevalence, clinical significance and prediction of gastric varices in patients
      with hepatocellular carcinoma. METHODOLOGY: From 1998 to 2000, we reviewed 304
      patients with hepatocellular carcinoma receiving upper gastrointestinal
      endoscopic examinations. Patients' clinical characteristics, physical findings,
      laboratory data, image studies, endoscopic examinations and treatment were
      reviewed. RESULTS: Among 304 patients with HCC, twenty-one (6.9%) had gastric
      varices among 304 patients with hepatocellular carcinoma. The location of gastric
      varices were the posterior wall in 12 (57%), the lesser curvature in 1 (5%), the
      greater curvature in 4 (19%) and the fundus in 4 (19%). Three (14%) of these 21
      patients with hepatocellular carcinoma and gastric varices had clinical evidence
      of bleeding. One of them died due to uncontrollable bleeding. Child-Pugh
      classification, hepatic encephalopathy, portal vein or splenic vein dilatation,
      ascites, splenomegaly, albumin level, prothrombin time and platelet count were
      significantly different between hepatocellular carcinoma patients with gastric
      varices and without gastric varices under the univariate analysis. Ascites (Odds
      ratio: 5.45; 95% confidence interval: 2.12-14.01) and portal vein or splenic vein
      dilatation (Odds ratio: 4.38; 95% confidence interval: 1.77-10.86) were the two
      most important predictors under the stepwise logistic regression analysis.
      CONCLUSIONS: The prevalence of gastric varices in patients with hepatocellular
      carcinoma is 6.9% and the risk of bleeding is low in this study. The Predictors
      of gastric varices among hepatocellular carcinoma are related to liver cirrhosis,
      Child-Pugh classification, hepatic encephalopathy, portal vein or splenic vein
      dilatation, ascites, splenomegaly, albumin level, prothrombin time and platelet
      count.

PMID- 14571796
TI  - Antioxidant and anti-inflammatory effects of a diet supplemented with sesamin on
      hepatic ischemia-reperfusion injury in rats.
AB  - BACKGROUND/AIMS: The antioxidant and anti-inflammatory properties of sesamin (a
      non-fat constituent of sesame oil) have been attributed to an increased
      accumulation of dihomo-y-linolenic acid, a precursor of 1-series prostaglandins,
      and the decreasing production of proinflammatory 2-series prostaglandins and 4
      series leukotrienes by inhibiting the delta-5 desaturase activity. We
      investigated the effects of a diet containing sesamin on hepatic ischemia
      reperfusion injury in rats. METHODOLOGY: After feeding rats either a basal diet
      (control group) or a diet supplemented with sesamin (sesamin group) for 14 days,
      the rats underwent 60 minutes of partial hepatic ischemia and 3 hours of
      reperfusion. The phospholipid fatty acid composition of both liver and lung
      tissue specimens were then analyzed. The plasma levels of leukotriene B4 and
      PCOOH (phosphatidylcholine hydroperoxide) were also determined. RESULTS: The
      consumption of the dietary sesamin resulted in a significant increase in the
      dihomo-y-linolenic acid content in the tissue phospholipids of the liver and lung
      specimens. The amounts of polyunsaturated fatty acids in the lungs subjected to
      the ischemia-reperfusion injury were well preserved in the animals from the
      sesamin group. Despite a lack of differences in the levels of arachidonic acid,
      the plasma levels of leukotriene B4 in the rats fed dietary sesamin (88 +/- 15
      pg) tended to be lower (P = 0.07) than those fed the control diet (110 +/- 20
      pg). Furthermore, the plasma concentrations of PCOOH in the sesamin group (130 +/
      62 pmol) were also significantly lower (P < 0.05) than those in the control
      group (223 +/- 33 pmol). CONCLUSIONS: These findings indicate that a diet
      containing sesamin may thus reduce hepatic ischemia-reperfusion injury by
      inducing both antioxidant and anti-inflammatory activities.

PMID- 14571798
TI  - Multifocal hepatocellular carcinoma in patients undergoing living-related liver
      transplantation.
AB  - Many institutions apply the indications for living-related liver transplantation
      in patients with hepatocellular carcinoma based on the Milan criteria, which
      state that transplantation is not indicated when more than three foci of disease
      are present. However, the relationship between the number of foci identified
      preoperatively and the number detected on pathologic examination of the surgical
      specimen is unknown. The case of a 66-year-old Japanese woman with cirrhosis
      secondary to type C viral hepatitis who developed hepatic failure secondary to
      multifocal hepatocellular carcinoma is presented. Three foci of hepatocellular
      carcinoma were identified radiologically preoperatively. Following successful
      living-related liver transplantation, pathologic examination of the surgical
      specimen revealed that six foci of hepatocellular carcinoma and one dysplastic
      nodule were present. Although the number of foci of hepatocellular carcinoma is a
      predictor of recurrence and > 3 is a relative contraindication to
      transplantation, lesions undetected radiologically (such as dynamic computed
      tomography) are unlikely to have metastatic or invasive potential because they
      have yet to evolve a capillary blood supply and still receive their nutrition via
      hepatic sinusoids on immunohistochemical and radiological findings. Foci of
      hepatocellular carcinoma undetected preoperatively are unlikely to effect
      prognosis when total hepatectomy is performed in the context of living-related
      liver transplantation.

PMID- 14571797
TI  - Splenic embolization in treatment of portal vein occlusion deferring liver
      transplantation.
AB  - The number of liver transplantations performed in this country is limited to the
      availability of cadaver liver donors, which are always short of demand.
      Deterioration of patient's clinical condition during the long wait for a
      compatible donor usually casts a poor prognosis on the patient. We report a 6
      year-old girl who underwent splenic artery embolization as an alternative
      procedure due to a life-threatening clinical condition while liver graft was not
      immediately available. She was a case of idiopathic portal hypertension with
      portal vein occlusion that had resulted in splenomegaly, pancytopenia, gastric
      and esophageal varices. Living graft transplantation was contraindicated due to
      portal vein lesion. She was listed as high-urgency for liver transplantation as
      she developed repeated esophageal variceal bleeding requiring frequent
      sclerotherapy and admission to the intensive care unit. Prevention of the ongoing
      worsening clinical complications, improvement of hematological disorders and
      correction of hypersplenism was achieved right after splenic artery embolization.
      The patient resumed normal daily life and has been successfully eliminated from
      the waiting list of liver transplantation. We conclude that this is a safe and
      effective alternative to splenectomy that might call of further liver
      transplantation.

PMID- 14571799
TI  - Hepatobiliary cystadenocarcinoma connected to the hepatic duct: a case report and
      review of the literature.
AB  - We present a rare case of hepatobiliary cystadenocarcinoma with biliary
      communication. A 74-year-old woman had a liver cyst that had enlarged from 5 cm
      to 8 cm in diameter over the last 2 years. A mural nodule, 1 cm in diameter, was
      first demonstrated by computed tomography in a multilocular cyst in segment IV.
      The nodule showed hypervascularity at angiography and computed tomography during
      arteriography. Percutaneous transhepatic cystography demonstrated a communication
      between the cyst and the biliary tract. The cyst was filled with mucinous and
      gelatinous fluid and was revealed to contain cancer cells. The patient underwent
      total tumor extirpation with the surrounding hepatic parenchyma. We confirmed and
      closed the biliary fistula connected to the right hepatic duct. Histologically,
      the cyst wall was composed of cystadenoma and the mural nodule showed in situ
      papillary adenocarcinoma. The patient is doing well 9 months after surgery.
      Complete tumor extirpation and closing of the biliary fistula is the treatment of
      choice.

PMID- 14571800
TI  - Liver metastasis of rectal cancer with intraluminal growth in the extrahepatic
      bile duct.
AB  - Metastatic liver tumors are considered to have a tendency for expansive growth
      and rarely invade the bile duct. We recently encountered a resected case of liver
      metastasis from rectal cancer with intraluminal growth in the extrahepatic bile
      duct with a successful left trisegmentectomy of the liver. A 54-year-old woman
      underwent a posterior total pelvic exenteration for advanced rectal cancer.
      Ultrasonography and computed tomography four months after the first operation
      demonstrated a solitary occupied lesion in the liver with dilation of the left
      hepatic duct. Endoscopic retrograde cholangiopancreatography disclosed a filling
      defect in the intra- to extrahepatic bile duct. Liver metastasis from rectal
      cancer with intraluminal growth in the bile duct was suspected despite a
      consideration of primary bile duct cancer. A left trisegmentectomy of the liver
      and resection of the extrahepatic bile duct with a right hepatojejunostomy were
      performed. The tumor had invaded the intrahepatic bile duct and had developed
      intraluminally in the extrahepatic bile duct. Tumor thrombi were microscopically
      found in the bile duct of the left caudal lobe. Liver metastasis arising from
      colorectal cancer with intraluminal growth in the bile duct is rare, however we
      encountered such a case with a successful resection involving a left
      trisegmentectomy of the liver.

PMID- 14571801
TI  - Spontaneous complete regression of hepatocellular carcinoma with portal vein
      tumor thrombus.
AB  - We report herein a case of spontaneous complete regression of hepatocellular
      carcinoma with portal vein tumor thrombus. A 69-year-old Japanese man with
      chronic hepatitis C was admitted to our hospital, because of a large mass in the
      right hepatic lobe. He was diagnosed with hepatocellular carcinoma based on
      computed tomography and the elevated serum levels of alpha-fetoprotein. Abdominal
      angiography revealed portal vein tumor thrombus. Approximately 2 months after the
      initial diagnosis, alpha-fetoprotein had decreased to a normal range. Under a
      diagnosis of hepatocellular carcinoma, a right hepatic lobectomy was performed,
      and histological examination of the resected specimen revealed no viable tumor
      cells. The patient is alive 1 year after the surgery without evidence of
      recurrence.

PMID- 14571802
TI  - A crescent-shaped sparing proximal to a liver tumor may indicate underlying
      portal tumor thrombus.
AB  - A primary or metastatic liver tumor sometimes blocks portal venous flow and
      causes a focal sparing in the fatty liver. We herein report a case of segmental
      sparing due to the portal tumor thrombus extending from the metastatic liver
      tumor. The present case demonstrates characteristic computer-associated
      tomographic findings, a distal oval hypodense tumor with proximal "crescent
      shaped sparing", which may indicate underlying portal tumor thrombus at the apex
      of the sparing.

PMID- 14571803
TI  - Successful diagnosis and resection of icteric type hepatocellular carcinoma.
AB  - We report a rare case of icteric type hepatocellular carcinoma with successful
      preoperative diagnosis and curative resection. A 50-year-old man was admitted to
      our hospital with fever elevation and jaundice. Endoscopic retrograde
      cholangiography revealed a tumor at the hepatic hilum, which caused obstruction
      of the right and left hepatic duct. The tumor was suspected of being a hilar
      cholangiocarcinoma, but it was diagnosed as being a hepatocellular carcinoma by
      endoscopic retrograde bile duct biopsy. After percutaneous transhepatic biliary
      drainage a right hemihepatectomy was performed. Subsequent pathological finding
      showed the tumor to be moderately-differentiated hepatocellular carcinoma
      (Edmondson III) which invaded into the right hepatic duct. The patient survived
      for three years without recurrence. Although patients with icteric type
      hepatocellular carcinoma have been reported to have a poor prognosis, earlier
      diagnosis and curative resection may occasionally bring them an improved
      prognosis.

PMID- 14571805
TI  - Radiofrequency ablation as a salvage procedure for ruptured hepatocellular
      carcinoma.
AB  - Spontaneous rupture of hepatocellular carcinoma is a distinct presentation
      causing acute abdomen. Different treatment approaches have been advocated
      including emergency hepatectomy, initial hemostasis by hepatic artery ligation or
      transarterial embolization and second-stage hepatectomy. Unrecognized ruptured
      hepatocellular carcinoma during laparotomy is often encountered in countries
      where the incidence of hepatocellular carcinoma is low. Radiofrequency ablation
      is a new localized thermal ablative technique for the treatment of unresectable
      hepatic tumors including hepatocellular carcinoma. We report a case where
      radiofrequency ablation was used as a salvage procedure for ruptured
      hepatocellular carcinoma during emergency laparotomy.

PMID- 14571804
TI  - Fibrolamellar hepatocellular carcinoma with a recurrence of classic
      hepatocellular carcinoma: a case report and review of Oriental cases.
AB  - A 72-year-old Chinese male, hepatitis B carrier, received a right hepatic
      trisegmentectomy in 1997 for fibrolamellar hepatocellular carcinoma. Serum alpha
      fetoprotein was in the normal range until two years after the operation, a rapid
      increase to 241 ng/mL occurred and computed tomography showed a 2-cm-sized
      recurrent nodule in the caudate lobe. Because computed tomography
      arterioportography showed additional multifocal nodules in the residual liver,
      transarterial embolization was performed. Four months after the first
      transarterial embolization, the caudate tumor grew to 6 cm and serum alpha
      fetoprotein increased to 6090 ng/mL. Prior to the second transarterial
      embolization, this new hepatic lesion received a biopsy and showed a
      characteristic feature of classic hepatocellular carcinoma, which was different
      from the previous one. Four months after the second transarterial embolization,
      computed tomography showed no recurrent tumor and serum alpha-fetoprotein
      subsequently normalized. Twenty-two months after the first transarterial
      embolization, a 2.5-cm-sized tumor recurred again at the lateral segment. At this
      time, serum alpha-fetoprotein (3.6 ng/mL) was not elevated. He received the third
      transarterial embolization and is still alive. Recurrence of fibrolamellar
      hepatocellular carcinoma after hepatic resection has been reported to be high,
      but a case report with a character of muticentric, multifocal, and metachronous
      recurrences of fibrolamellar and classic type hepatocellular carcinoma is very
      rare. This is the second case report in the literature.

PMID- 14571806
TI  - Hepatocellular carcinoma fed by an aberrant posterior right hepatic artery.
AB  - An aberrant hepatic artery arising from the dorsal pancreatic artery is extremely
      rare, although the arterial blood supply to the liver is variable. A 56-year-old
      Japanese man was admitted to our hospital with a lesion in the right hepatic
      lobe. Serum concentrations of alpha-fetoprotein, carcinoembryonic antigen, and
      carbohydrate antigen 19-9 were within the reference range. Abdominal
      arteriography showed a hypervascular lesion measuring 3.0 cm in diameter in the
      right hepatic lobe. The left hepatic artery, the middle hepatic artery, and the
      anterior branch of the right hepatic artery were derived from the common hepatic
      artery, while the posterior branch originated from the dorsal pancreatic artery.
      Computed tomography performed during arteriography via the common hepatic artery
      showed an arterial perfusion defect in the posterior segment of the right hepatic
      lobe and enhancement of the ventral portion of the tumor, while the dorsal
      portion was not enhanced. However, the dorsal portion of the tumor was enhanced
      when arteriography was performed via the dorsal pancreatic artery. A limited
      hepatic resection was performed. Histologically, the tumor was a moderately
      differentiated hepatocellular carcinoma with a thick trabecular pattern.

PMID- 14571807
TI  - A case of hepatocellular carcinoma (HCC): treatment with local application of
      alcohol and interleukin 2 (IL-2).
AB  - A case of an inoperable hepatocellular carcinoma due to liver cirrhosis is
      presented. Surgical treatment was not clinically warranted. So we decided to
      induce tumor necrosis by intratumoral injections of 10 mL of ethanol followed by
      two treatments with 9 x 10(6) U Chiron interleukin-2 with an interval of 1 month.
      This ethanol-interleukin-2 cycle was repeated three times with intervals of 6
      months. Interleukin-2 injections were given by a fine needle, under ultrasound
      control in the periphery and in the center of the tumor. The initial size of the
      tumor was 55-60 mm. During the follow-up period of 2 years the tumor size
      remained relatively unchanged. The patient died due to gastric hemorrhage. The
      treatment elicited no adverse clinical effects. The clinical status improved
      greatly after this treatment. Local interleukin-2 application after alcohol
      induced tumor ablation might be an alternative if surgical treatment is not
      warranted.

PMID- 14571808
TI  - Experience with end-to-loop pancreaticoenteroanastomosis in
      pancreaticoduodenectomy.
AB  - BACKGROUND/AIMS: Early results of 151 pancreaticoduodenectomies were
      retrospectively studied. METHODOLOGY: Pancreaticoduodenectomy was performed in
      129 (85.5%) patients with periampullary carcinoma, in 18 (11.9%) with chronic
      pancreatitis and in 4 (2.7%) patients with other pathologies.
      Pancreaticoenteroanastomosis was placed in 125 (82.8%) patients, end-to-loop
      virsungoenteroanastomosis according to V. Onopriev and A. Manuilov was applied in
      79 (52.3%) patients (group I). A routine end-to-side anastomosis (group II) was
      used in 46 (30.5%) cases; other techniques of the pancreatic stump management
      were performed in 26 patients. RESULTS: The lethality rate was 11.3%. It varied
      depending on the type of pancreaticoduodenectomy completion. Three patients with
      the end-to-loop virsungoenteroanastomosis died in the early postoperative period,
      compared with 7 (15.2%) deaths in the group with the end-to-side anastomosis. The
      incidence of postoperative complications was 32.9% in group I, 52.2% in group II.
      In group I there were no cases of failure of pancreatoenteroanastomosis, in group
      II this complication was present in 2 (4.4%) patients. Leakage of the pancreatic
      secretions into the abdominal cavity was revealed in 4 (5.1%) patients of group
      I, and in 10 (21.7%) of group II. CONCLUSIONS: The technique of the end-to-loop
      virsungoenteroanastomosis allows the improvement of early results of
      pancreaticoduodenectomy due to reduction in infectious and inflammatory
      complications.

PMID- 14571809
TI  - Etiology of acute pancreatitis--a multi-center study in Taiwan.
AB  - BACKGROUND/AIMS: Little is known about the etiology of acute pancreatitis in
      Taiwan. The aim of this study was to evaluate the current etiology of acute
      pancreatitis in Taiwan by a multi-center cooperative study. METHODOLOGY: Patients
      with acute pancreatitis were collected from 8 major leading hospitals located at
      northern, southern, middle and eastern Taiwan from July 1, 1998 to June 30, 2000.
      The diagnosis of acute pancreatitis was based on characteristic clinical signs
      and symptoms and three-fold elevation of serum amylase/lipase level or positive
      evidence in imaging studies. The etiology was attributed to alcohol, gallstones,
      hypertriglyceridemia, miscellaneous causes, and idiopathic causes. RESULTS: In
      total 1,193 patients with acute pancreatitis were identified. There were 852
      (71.4%) men and 341 (28.6%) women with a mean age of 52.5 years, ranging from 9
      to 100 years. Etiology was identified as alcohol in 423 (33.6%), gallstones in
      407 (34.1%), hypertriglyceridemia in 147 (12.3%), miscellaneous causes in 109
      (9.1%), and idiopathic causes in 107 (9.0%). Patients with alcohol-related acute
      pancreatitis were the youngest (mean age: 41.5 years), while those with gallstone
      pancreatitis were the eldest (mean age: 64.1 years) (p < 0.001). The predominant
      cause of acute pancreatitis in women is gallstones, while alcohol is the leading
      cause of acute pancreatitis in Taiwanese males. In northern Taiwan, gallstone is
      the major cause of acute pancreatitis, while alcohol is the predominant etiology
      in middle, southern, and eastern Taiwan. CONCLUSIONS: Alcohol has become the
      predominant cause of acute pancreatitis in Taiwan recently. Ecological and gender
      differences play important roles in the etiology of acute pancreatitis in Taiwan.

PMID- 14571810
TI  - Pancreatic fistula after pancreatic head resection; incidence, significance and
      management.
AB  - BACKGROUND/AIMS: Anastomotic leak at the pancreatojejunostomy remains a common
      and dreaded complication after pancreaticoduodenectomy. Our aim was to determine
      the incidence, presentation, methods of management, and preoperative and
      postoperative factors that influence the clinical outcome. METHODOLOGY: We
      reviewed our collective experience with 70 consecutive patients from 1985 to 2000
      for a variety of pathologic indications. Clinical, biochemical, intraoperative
      and postoperative factors were reviewed in an attempt to determine prognostic
      factors. RESULTS: Nine patients (12%) developed a pancreatic anastomotic leak as
      determined by increased amylase in drainage fluid (70%), were clinically
      insignificant and were managed by simple maintenance of intraoperatively placed
      drains. Although octreotide was used therapeutically in 4 patients (44%),
      significant, objective response was noted in all patients. Of the clinical,
      biochemical, intraoperative and postoperative factors reviewed to determine
      prognostic factors, a large amount of postoperative pancreatic juice output (P =
      0.02) was a significant risk factor for pancreatic fistula formation.
      CONCLUSIONS: We conclude that most anastomotic leak at pancreaticoenterostomy
      after pancreaticoduodenectomy can be managed conservatively. Use of octreotide to
      aid in closure of the pancreatic leak was satisfactory.

PMID- 14571811
TI  - Is pancreaticoduodenectomy justified for septuagenarians and octogenarians?
AB  - BACKGROUND/AIMS: Almost all of the studies described elderly as beginning at the
      age 70 and very few focused on the group of patients over 80 years of age. This
      study was undertaken to compare the surgical risk and prognosis between
      septuagenarians and octogenarians undergoing pancreaticoduodenectomy and to
      clarify whether or not pancreaticoduodenectomy is justified in octogenarians.
      METHODOLOGY: Among 276 patients with periampullary lesions undergoing
      pancreaticoduodenectomy between 1982 and 2000, octogenarians and septuagenarians
      were identified. The study concentrated on the surgical risks and outcomes.
      RESULTS: There were 16 (6%) octogenarians and 82 (30%) septuagenarians among our
      276 patients undergoing pancreaticoduodenectomy. Surgical mortality did not
      significantly increase in octogenarians (13%), as compared to septuagenarians
      (12%). Surgical morbidity was also similar in both groups (51% in octogenarians
      vs. 56% in septuagenarians). Octogenarians needed more frequent care in the
      intensive care unit (69%) postoperatively than septuagenarians (27%), p = 0.001.
      There was no significant difference in survival, (median survival = 16 months for
      septuagenarians and 17.6 months for octogenarians), p = 0.137. About half of each
      group (44.2% septuagenarians and 54.5% octogenarians) still died of the
      underlying periampullary lesions, p = 0.771. CONCLUSIONS: Surgical risk did not
      significantly increase and prognosis was similar in octogenarians after
      pancreaticoduodenectomy, as compared to septuagenarians. Therefore,
      pancreaticoduodenectomy is justified not only in septuagenarians but also in
      octogenarians if carefully selected.

PMID- 14571812
TI  - Pancreatitis associated with pancreaticobiliary maljunction.
AB  - BACKGROUND/AIMS: Pancreaticobiliary maljunction is a rare anomaly, but causes
      various pathological conditions in the biliary tract and the pancreas. This study
      aims at clarifying the features of pancreatitis associated with
      pancreaticobiliary maljunction. METHODOLOGY: A total of 100 patients with
      pancreaticobiliary maljunction were reviewed. Clinical findings and
      cholangiopancreatographic results in patients with acute or chronic pancreatitis
      associated with pancreaticobiliary maljunction were analyzed. RESULTS: Of 100
      patients, 14 had pancreatic disorders: acute pancreatitis (n = 3), chronic
      pancreatitis (n = 5), hyperamylasemia (n = 4), and pancreatic carcinoma (n = 2).
      The acute pancreatitis was mild (n = 3) and relapsing (n = 2). In patients with
      chronic pancreatitis, pancreatic stones (n = 2) and radiolucent protein plugs (n
      = 2) were detected only in the dilated common channel or in the main pancreatic
      duct near the common channel. Two patients received cyst-duodenostomy in the
      infant developed chronic pancreatitis 11 and 27 years later. CONCLUSIONS: Acute
      or chronic pancreatitis was sometimes associated with pancreaticobiliary
      maljunction. These pancreatitis cases showed different clinical and
      pancreatographic findings from others. These differences might be due to the
      peculiar mechanism that they were induced by bile reflux into the pancreatic duct
      via the anomalous connection.

PMID- 14571813
TI  - Comparison of tumor marker CA 242 with CA 19-9 and carcinoembryonic antigen (CEA)
      in pancreatic cancer.
AB  - BACKGROUND/AIMS: Although there are a variety of tumor markers used for diagnosis
      of pancreatic carcinoma, the sensitivity and specificity of those markers have
      not yet reached an ideal level. The aim of this study was to compare the
      diagnostic value of CA 242 with CA 19-9 and CEA in the patients with pancreatic
      cancer. METHODOLOGY: Serum CA 242, CA 19-9 and CEA levels were determined in 135
      subjects in the following groups: Pancreatic cancer (n = 40), cholangiocellular
      carcinoma (n = 15), hepatocellular carcinoma (n = 10), cirrhosis (n = 7), chronic
      active hepatitis (n = 7), choledochal stone (n = 12), chronic pancreatitis (n =
      9), acute pancreatitis (n = 6), and healthy controls (n = 29). RESULTS: An
      elevated serum CA 242 concentration (> 20 U/mL) was found in 30 out of 40 (70%)
      (mean; 2163 +/- 838 U/mL) patients with pancreas cancer, in 11 out of 15 patients
      with cholangiocellular carcinoma (93.3%) (mean 916 +/- 529 U/mL), in none of
      patients with hepatocellular carcinoma and healthy controls. Slightly elevated CA
      242 concentration was found in 6 out of 41 patients with benign hepatobiliary and
      pancreatic disease (range 0.4-97.8 U/mL) (1 acute pancreatitis, 2 chronic
      pancreatitis, 1 cirrhosis, 2 choledochal stone). Mean serum CA 242, CA 19-9 and
      CEA levels of the pancreas cancer group were significantly higher than those of
      the other groups except the cholangiocellular carcinoma group. There was no
      significant difference between the stage of pancreas cancer regarding mean serum
      CA 242, CA 19-9 and CEA level. There was positive correlation between serum CA
      242 and CA 19-9 level. In the pancreas cancer, the sensitivity of CA 242, CA 19-9
      and CEA was 75%, 80%, 40%, respectively and the specificity of those markers was
      85.5%, 67.5% and 73%, respectively. CONCLUSIONS: In conclusion, the advantage of
      CA 242 compared to CA 19-9 is that its specificity is higher than that of CA 19-9
      in the diagnosis of pancreas cancer.

PMID- 14571814
TI  - Pancreatic metastasis from leiomyosarcoma in the back.
AB  - A tumor in the head of the pancreas was detected in a 39-year-old man who had an
      excision of leiomyosarcoma in the back 2 years before. The patient underwent
      pancreatoduodenectomy. The surgical specimen revealed leiomyosarcoma metastatic
      to the pancreas. The patient is still alive following two resections in the lung
      and the abdominal wall. To the best of our knowledge, this is the first report of
      a successfully resected case of pancreatic metastasis from a leiomyosarcoma.

PMID- 14571815
TI  - Surgical treatment for right pleural effusions caused by pancreaticopleural
      fistula.
AB  - A 56-year-old man with a history of alcohol abuse presented with exertional
      dyspnea. A chest radiography showed a massive right pleural effusion with
      sanguineous pleural fluid and an amylase level of 97,188 IU/L. Despite
      conservative treatment with no oral intake, total parenteral nutrition and
      repeated thoracentesis, the pleural effusion was persistent and intrathoracic
      infection was suspected. Surgical intervention was proposed and a preoperative
      endoscopic retrograde cholangiopancreatography revealed disruption of the mid
      pancreatic duct and a fistulous tract. A middle segment pancreatectomy was
      performed for removal of the disrupted portion of the main pancreatic duct and
      reconstruction of the distal pancreas was completed by end-to-side Rouxen-Y
      pancreatojejunostomy. The patient had a good postoperative course and was
      discharged on the 29th postoperative day. He has remained well during the 9
      months of follow-up.

PMID- 14571816
TI  - Cystic lymphangioma of the pancreas: anatomoclinical, diagnostic and therapeutic
      considerations regarding three personal observations and review of the
      literature.
AB  - Cystic lymphangioma is a very rare pathology and the pancreatic ones represent an
      exceptional report that must be considered in the differential diagnosis with
      others and more frequent cystic lesions of the pancreas. In this paper we
      describe three cases of cystic lymphangiomas of the pancreas observed in our
      Institute and we report on the literature review. Anatomopathological, clinical
      and therapeutics aspects of pancreatic cystic lymphangioma were analyzed for a
      better knowledge of this cystic lesion and to recognize some specific findings
      that could allow a preoperative diagnosis and, subsequently, a proper treatment.

PMID- 14571817
TI  - Long-term survivor without recurrence after resection of simultaneous solitary
      pancreatic metastasis from thyroid medullary carcinoma.
AB  - A 43-year-old Japanese man had an increasing level of serum CEA pointed out by
      annual physical check-ups. No abnormal findings were detected in the lungs or
      gastrointestinal tract. The only pathological lesions were a 1.5-cm-sized nodule
      in the pancreatic tail and a 5-cm-sized thyroid tumor. The thyroid tumor was
      shown to be medullary carcinoma by aspiration cytology. He underwent total
      thyroidectomy with extensive lymph node dissection. After thyroid surgery, the
      patient received distal pancreatectomy 2 weeks later. Pathological examination
      revealed the pancreatic tumor to be a metastasis of thyroid medullary carcinoma.
      The patient is alive and well without recurrence 5 years after thyroidectomy and
      pancreatectomy. The serum levels of CEA and calcitonin remain within normal
      limits. Thus, the patient seems to have had a solitary metastatic tumor from
      thyroid medullary cancer.

PMID- 14571818
TI  - A pancreatic-induced intramural duodenal hematoma: a case report and literature
      review.
AB  - Spontaneous intramural duodenal hematomas are not frequent and generally are
      related with an anticoagulant treatment. Pancreatic origin has seldom been
      described and the treatment is always controversial. We report a new case of a
      pancreatitis-induced intramural duodenal hematoma that was conservatively managed
      and we review the literature.

PMID- 14571819
TI  - Tumor thrombus in the splenic vein originated from gastric carcinoma that
      produced alpha-fetoprotein.
AB  - A 72-year-old man was referred with an endoscopic diagnosis of Borrmann 2 type
      advanced gastric cancer. Further examination revealed tumor thrombus in the
      splenic vein and high serum level of alpha-fetoprotein without liver disease.
      Intraoperative ultrasonography revealed that tumor thrombus originated from
      gastric cancer extended to the splenic vein through the left gastric vein. Total
      gastrectomy combined with distal pancreatectomy and splenectomy was done to
      obtain complete resection of cancer and tumor thrombus. Tumor and its thrombus in
      the splenic vein were diagnosed as a poorly differentiated adenocarcinoma that
      produced alpha-fetoprotein. We report the case, and discuss about the gastric
      cancer with portal tumor thrombus and high serum levels of alpha-fetoprotein.

PMID- 14571820
TI  - Splenic embolization in a Jehovah's Witness: role of recombinant human factor
      VIIa.
AB  - A case of a 50-year-old Jehovah's Witness with cryptogenic cirrhosis, severe
      portal hypertension and a coagulopathy, who underwent splenic embolization to
      improve the platelet count after receiving recombinant human Factor VIIa, is
      reported. Following the infusion of recombinant human Factor VIIa, the
      coagulopathy was rapidly corrected and it became possible to safely embolize her
      spleen. The changes in prothrombin time, international normalized ratio and
      activated partial thromboplastin time as well as thrombomodulin, tissue factor
      and plasminogen activator inhibitor after the infusion are presented. As a result
      of the splenic embolization, her platelet count normalized and she has been
      listed for liver transplantation.

PMID- 14571821
TI  - Outcome of patients with inconsistent results from 13C-urea breath test and
      bacterial culture at the time of assessment of Helicobacter pylori eradication
      therapy in Japan.
AB  - BACKGROUND/AIMS: At the assessment of eradication therapy of Helicobacter pylori,
      the results of 13C-urea breath test and other methods such as bacterial culture
      are occasionally inconsistent. In this study, we examined the outcomes of
      inconsistent results. METHODOLOGY: Four hundred and four patients with peptic
      ulcer who were H. pylori-positive and who had completed eradication therapy were
      studied. Bacterial culture, rapid urease tests and 13C-urea breath test were
      performed between one and three months after the end of the therapy. The cut-off
      value for the 13C-urea breath test used originally in this study was 2.5 per mil.
      We investigated the outcome of inconsistent results by following up the patients
      every 6 to 12 months. RESULTS: At the initial assessment of eradication therapy,
      we observed inconsistent results with bacterial culture and 13C-urea breath test
      in 43 of 404 patients. Most of them (40 of 43) were culture-negative but urea
      breath test-positive, and the majority became negative for both tests. Based on
      the follow-up results, the optimum value for 13C-urea breath test at the
      assessment of eradication therapy was found to be 3.5 per mil. CONCLUSIONS: We
      found that outcomes of inconsistent results were variable, indicating the
      importance of the follow-up of patients after eradication therapy of H. pylori.

PMID- 14571822
TI  - Efficacy of endoscopic surveillance of the upper gastrointestinal tract following
      distal gastrectomy for early gastric cancer.
AB  - BACKGROUND/AIMS: How endoscopy can be used in the follow-up of the upper
      gastrointestinal tract in patients who underwent gastrectomy for early gastric
      cancer remains unclear. METHODOLOGY: Two-hundred and ten patients (137 males and
      73 females, aged at initial gastrectomy 27-86, average age 56.5) were followed in
      the present study. Results of follow-up endoscopy of all patients, pathologic
      diagnoses of secondary tumors and interval between gastrectomy and detection of
      secondary tumor were reviewed. Cumulative incidence rate of second tumors in the
      upper gastrointestinal tract was then analyzed. RESULTS: Secondary tumor was
      observed by follow-up endoscopy in 7 patients including two gastric, one
      esophageal, one duodenal carcinoma and 3 gastric adenomas. The interval between
      initial gastrectomy and diagnosis of secondary tumor ranged from 20 to 71 months
      (average 51.7 months). All carcinomas were early stage and localized within the
      mucosa. Three patients with secondary cancer were successfully treated by
      endoscopic mucosal resection. The cumulative incidence rate of secondary cancer
      in the gastric remnant, esophagus and duodenum at six years after initial
      gastrectomy was 1.0, 0.8 and 0.5%, respectively. The overall incidence rate of
      secondary tumors of the upper gastrointestinal tract at six years after distal
      gastrectomy was 4.1%. CONCLUSIONS: The present findings indicate that annual
      follow-up endoscopy of the upper gastrointestinal tract after gastrectomy for
      early gastric cancer can be introduced to detect carcinoma at an early stage,
      thus improving the survival rate of gastrectomy patients.

PMID- 14571823
TI  - Predictive value of uric acid in gastric mucosal damage in hemodialysis patients.
AB  - BACKGROUND/AIMS: Uric acid, which has an antioxidant effect, is present at very
      high serum levels in hemodialysis patients, but its effect has not yet been
      clarified. In this study we investigated whether or not serum uric acid levels
      could be associated with gastric mucosal damage in hemodialysis patients.
      METHODOLOGY: We performed endoscopy in 53 patients who were on dialysis for more
      than two months and determined the relationship between serum uric acid levels,
      clinical features and gastric mucosal damage. RESULTS: Of 53 patients,
      gastroduodenal ulcer was found in 13 patients (Ulcer group), gastritis lesions in
      25 patients (Gastritis group) and no pathological findings in 15 patients (Normal
      group). Serum uric acid levels before the dialytic session were remarkably higher
      in the Ulcer group than in the Normal (P < 0.01) or Gastritis group (P < 0.05).
      There was also a significant difference between the Gastritis and Normal groups
      in the serum uric acid levels (P < 0.05). Alcohol intake and noncompliance
      resulted in a significant increase in both gastric mucosal damage (P = 0.009 and
      P = 0.010) and serum uric acid levels (P < 0.05 and P < 0.01). Serum uric acid
      levels were markedly decreased after treatment with a proton pump inhibitor or H2
      blocker. CONCLUSIONS: In hemodialysis patients alcohol intake and noncompliance
      contribute to the increase in serum uric acid levels and gastric mucosal damage,
      and serum uric acid levels have predictive values in gastric mucosal damage.

PMID- 14571824
TI  - Should gastric cancer with peritoneal metastasis be treated surgically?
AB  - BACKGROUND/AIMS: This study was attempted to elucidate the role of surgery in
      patients with gastric carcinoma and peritoneal dissemination. METHODOLOGY: A
      database of 128 patients was retrospectively examined with univariate and
      multivariate analyses after selecting 4 treatment factors, 7 tumor factors
      evaluated preoperatively, 2 tumor factors evaluated intraoperatively, and 2
      patient factors. RESULTS: The overall median survival time was 188 days. Median
      survival time was 259 days for patients who underwent resection, 173 days for
      those who underwent bypass operation, and 108 days for those who underwent
      laparotomy alone. Multivariate analysis revealed only four significant factors
      for prognosis including computed tomography findings of metastases to the lymph
      nodes of groups 2 and 3, distant metastasis, ascites, and postoperative status of
      the patients. Among these factors, the patient status was the most important
      factor for survival. In 70 patients with a preoperative bad status, the clinical
      factors affecting survival were analyzed by multivariate analysis exclusive of
      the postoperative patient status; ascites, resection, bypass operation, and
      postoperative chemotherapy were significant independent factors. There was no
      significant difference in safety, efficacy, or prognosis, between the procedures
      of resection and bypass. CONCLUSIONS: Surgical treatment is not recommended for
      patients with gastric cancer and peritoneal dissemination when their preoperative
      status is good. Palliative surgery should be selected when their status is bad.
      The primary tumor should be resected only when the patient has anemia due to
      bleeding from the primary tumor.

PMID- 14571825
TI  - 5-Fluorouracil, methotrexate, leucovorin, CDDP and epirubicin (FEPMTX): a wide
      spectrum regimen of salvage chemotherapy for high-grade advanced gastric cancer.
AB  - BACKGROUND/AIMS: Twenty-one patients with primary stage IV gastric cancer were
      treated with a wide-spectrum regimen, designated as FEPMTX therapy to establish
      an effective salvage chemotherapy. METHODOLOGY: FEPMTX therapy consisted of 5
      fluorouracil and the triple biochemical modulators in addition to epirubicin. The
      schedule comprised 3 days continuous administration of 5-fluorouracil (350
      mg/m2/day) and; methotrexate (MTX; 35 mg/m2) on day 1, calcium leucovorin (LV; 30
      mg/m2) on day 2 and 3, cisplatin (CDDP; 30 mg/m2) and epirubicin (20 mg/m2) on
      day 3 every 2 weeks in principle. RESULTS: Eleven partial responses, five no
      changes and five progressive diseases were obtained, and the response rate was
      52%. Ten patients (partial response 7, no change 2, progressive disease 1)
      received gastrectomy (resectability rate 48%). The survival of responders was
      significantly longer than that of non-responders (median survival time, 356 days
      vs. 152 days) while there was no significant prolongation by resection of the
      primary lesion. Adverse effects such as myelosuppression, anorexia and fatigue
      sometimes occurred, but were mild and the regimen was well tolerated by all the
      patients. CONCLUSIONS: FEPMTX is thought to be an effective regimen for
      neoadjuvant chemotherapy with longer survival and little toxicity for patients
      with high-grade advanced gastric cancer.

PMID- 14571826
TI  - Peritoneal recurrence of gastric adenocarcinoma after curative resection.
AB  - BACKGROUND/AIMS: Death from gastric carcinoma after curative resection is mostly
      due to recurrence. The most common recurrence is peritoneal dissemination, which
      represents 33 to 50% of total recurrence after curative gastrectomy. Since
      survival after peritoneal dissemination is very poor, selection of high-risk
      patients for further management after resection may contribute to better
      survival. METHODOLOGY: Based on a prospective database, a total of 1,092 patients
      with gastric carcinoma who underwent curative resection were included in this
      study. The incidence of peritoneal recurrence, disease-free interval and survival
      after peritoneal recurrence were determined. The clinicopathological factors
      including sex, age, tumor location, size, gross appearance, histological
      findings, depth of tumor invasion, lymph node status, tumor cell infiltration
      pattern were analyzed to see if there is any relationship with peritoneal
      dissemination. RESULTS: The incidence of peritoneal recurrence after curative
      resection was 13.46%. The mean disease-free interval was 14.2 months and the
      survival after peritoneal recurrence was 4.9 months in average. Almost all the
      clinicopathological factors were related with peritoneal recurrence, but only
      depth of tumor invasion, gross appearance and tumor infiltration pattern are
      closely associated with peritoneal tumor dissemination after multivariate
      analyses. CONCLUSIONS: Since the prognosis after peritoneal recurrence is so
      poor, selection of high-risk patients for further management after gastrectomy
      may be based on these three factors.

PMID- 14571827
TI  - Factors associated with pN3 stage tumors according to the TNM classification in
      advanced gastric cancer.
AB  - BACKGROUND/AIMS: The aim of the present study was to analyze factors associated
      with pN3-stage tumors, as classified according to the TNM Classification of
      Malignant Tumors, in patients who undergo curative resection for advanced gastric
      cancer. METHODOLOGY: A total of 391 patients with advanced gastric cancer (247
      males and 144 females; average age, 59.2 years) were enrolled in the present
      study. The numbers of dissected regional lymph nodes and positive nodes were
      assessed, and node stage was determined according to TNM. Patient survival and
      factors associated with pN3-stage tumors were then analyzed. RESULTS: The 5-year
      survival rate was 82.9% for the 132 N0 patients, 66.4% for the 154 N1 patients,
      41.1% for the 64 N2 patients and 21.1% for the 41 N3 patients. A significant
      difference was found between some of the curves (N0 and N1, p = 0.0012; N1 and
      N2, p = 0.0007; N2 and N3, p = 0.0055). In logistic regression analysis,
      independent factors associated with advanced gastric cancers with a pN3-stage
      tumor were tumor diameter (> 6 cm vs. < or = 6 cm, p = 0.0037), number of
      dissected nodes (> 30 vs. < or = 30, p = 0.0143), depth of invasion (T3 or T4 vs.
      T2, p = 0.0028) and microscopic type (undifferentiated vs. differentiated, p =
      0.0147). CONCLUSIONS: The results of the present study suggest that tumor
      diameter (> 6 cm), depth of invasion (T3 or T4) and microscopic type
      (undifferentiated type) are the most reliable indicators of pN3-stage tumors in
      patients who undergo curative resection for advanced gastric cancer.

PMID- 14571828
TI  - Indications of limited surgery for gastric cancer with submucosal invasion-
      analysis of 715 cases with special reference to site of the tumor and level 2
      lymph nodes.
AB  - BACKGROUND/AIMS: There is controversy as to whether limited or extended lymph
      node dissection should be performed for gastric cancer with submucosal invasion.
      METHODOLOGY: To clarify the indications of limited surgery for gastric cancer
      invading the submucosa, we retrospectively examined the incidence of lymph node
      metastases with regard to the location of the tumor and distant lymph node
      station in 715 patients who underwent curative gastrectomy with D2
      lymphadenectomy for gastric cancer with submucosal invasion. We classified the
      level 2 lymph nodes into four groups as follows: group 1 was defined as
      perigastric lymph nodes far from the primary tumors, group 2 as nodes around the
      left gastric and the common hepatic arteries, group 3 as nodes around the celiac
      axis, and group 4 as nodes along the splenic artery. RESULTS: The occurrence of
      the metastases to level 1 nodes was 14.5% (104 of 715) and that to level 2 nodes
      was 4.5% (32 of 715). Among the latter, metastases to group 1 lymph nodes were
      detected in 6 only in the lower third (2.1%) and that to group 2 in 5 in the
      upper third (6.2%), 9 in the middle third (2.6%), and 12 in the lower third of
      the stomach (4.1%). Metastases to groups 3 and 4 were only recognized in 2 in the
      middle third of the stomach (0.3%). Tumors less than 8 mm did not metastasize to
      lymph nodes and those less than 12 mm did not metastasize to distant ones.
      CONCLUSIONS: These results suggested that in gastric cancer invading the
      submucosa, it would be sufficient to dissect group 2 lymph nodes for tumors
      located at the upper third or the middle third of the stomach, and for tumors
      located in the lower third of the stomach nodes of groups 1 and 2 should be
      dissected. For tumors less than 8 mm in the diameter partial resection alone
      could do and for those less than 12 mm D1 dissection is recommended.

PMID- 14571829
TI  - One-week low-dose triple therapy without anti-acid treatment has sufficient
      efficacy on Helicobacter pylori eradication and ulcer healing.
AB  - BACKGROUND/AIMS: The aim of this study was to determine the efficacy of a 1-week
      low-dose proton pump inhibitor-based triple therapy without further acid
      suppression for cure of Helicobacter pylori infection and the ulcer healing in
      peptic ulcer disease. METHODOLOGY: Patients with endoscopically proven peptic
      ulcers who were H. pylori positive participated in this study. All patients were
      treated for 1 week with omeprazole 20 mg b.d., clarithromycin 250 mg b.d. and
      tinidazole 500 mg b.d., then patients were treated randomly for another 4 weeks
      with either omeprazole 20 mg once daily (OCM-O group; n = 40) or without acid
      suppressing agents (OCM group; n = 39). Patients were investigated endoscopically
      for H. pylori and ulcer status before treatment, four weeks (week 5) and 8 weeks
      later (week 9) after anti-H. pylori treatment. H. pylori infection was assessed
      by rapid urease test and histology. RESULTS: The eradication rates of H. pylori
      were 72.5% (95% CI: 59-86%) and 76.3% (95% CI: 63-90%) by intention-to-treat
      analysis and by per protocol analysis respectively in the OCM-O group and were
      87.2% (95% CI: 77-98%) and 97.1% (95% CI: 92-100%) by intention-to-treat analysis
      and by per protocol analysis respectively in the OCM group (p < 0.05 in per
      protocol analysis). In respect to ulcer healing status at week 5, 89.5% (34/38)
      of patients in the OCM-O group and 80% (28/35) of patients in the OCM group had
      healed ulcers; at week 9, 86.8% (33/38) of patients in the OCM-O group and 88.6%
      (31/35) of patients in the OCM group had healed ulcers (p = NS). When the ulcer
      status was analyzed in relation to the H. pylori status, at week 5 ulcer had
      healed in 84.4% (54/64) of patients with clearance of H. pylori infection and in
      88.9% (8/9) of those with persistent infection. At week 9, ulcer healing
      increased up to 93.8% (60/64) of patients with clearance of H. pylori infection
      and decreased to 44.4% (4/9) of patients with persistent infection. The adverse
      events (20%) were mild in these two treatment groups and no patients required
      discontinuation of the study medications. CONCLUSIONS: Continuation of
      antisecretory drug therapy beyond a one-week low-dose triple therapy consisting
      of omeprazole, clarithromycin and tinidazole is actually excessive regarding
      eradication efficacy and peptic ulcer healing.

PMID- 14571830
TI  - Docetaxel plus 5-fluorouracil for terminal gastric cancer patients with
      peritoneal dissemination.
AB  - BACKGROUND/AIMS: There are few reports on chemotherapy for poor prognosis
      terminal patients with peritoneal dissemination of gastric cancer, especially in
      those with renal dysfunction, because of the possibility of severe toxicity. We
      conducted a study of the combination of docetaxel and 5-fluorouracil for the
      treatment of these patients to improve quality of life because of its low
      toxicity. METHODOLOGY: Five patients were treated in this study. All patients had
      a large volume of carcinomatous fluid in the abdomen, without liver or distant
      metastasis. The respective doses of docetaxel and 5-fluorouracil were 60 mg/m2 on
      day 1 and 370 mg/m2 on days 1 to 5 by intravenous infusion. Patients received
      this treatment 2-7 times every 2-3 weeks. RESULTS: Grade III/IV toxicity
      occurred, consisting of neutropenia (100%) and diarrhea (40%). No patients
      developed renal dysfunction. Carcinomatous fluid volume diminished for 15-96
      days. Quality of life questionnaire score and performance status scale was
      significantly improved from 75-86 to 51-61 (p = 0.041) and 3-4 to 0-1 (p =
      0.039), respectively. All patients were able to leave hospital after this
      treatment. Four of five patients died and median survival time was 223 days. Two
      of five patients achieved partial response and three patients showed no response
      (response rate 40%). CONCLUSIONS: This new combination therapy had benefit for
      terminal patients with peritoneal dissemination of gastric cancer.

PMID- 14571832
TI  - New method for Billroth I reconstruction after distal gastrectomy.
AB  - Authors report a new technique for Billroth I reconstruction after distal
      gastrectomy using linear stapling devices, which is easier than conventional
      methods. The duodenum is divided 0.5 cm distal to the pyrolus ring, with a 55-mm
      linear stapler. The anterior wall of the duodenum is cut along the planned line
      of anastomosis with the gastric remnant. The anterior wall of the stomach is cut
      along the planned suture line having a length similar to that of the duodenum.
      The posterior walls of the stomach and the duodenum are placed back to back on
      the planned anastomotic line. End-to-end posterior anastomosis between the
      gastric remnant and the duodenum is simultaneously performed with gastrectomy
      using a 100-mm linear stapler. End-to-end anterior anastomosis is performed by
      hand. This technique has been used in 7 patients, and there have been no
      complications related to this procedure. Operative time was 152 +/- 16 min (range
      130 to 180 min) on average. It is an economical and easy procedure for Billroth I
      reconstruction.

PMID- 14571831
TI  - H. pylori decreases gastric mucin synthesis via inhibition of
      galactosyltransferase.
AB  - BACKGROUND/AIMS: Alterations of gastric mucin have been postulated as important
      pathogenic properties of Helicobacter pylori. In this study, we investigated
      gastric mucin synthesis in H. pylori-infected gastric mucosa by measuring UDP
      galactosyltransferase activity, a key enzyme for the synthesis of mucin, and the
      amount of intracellular mucin in the gastric mucosa. METHODOLOGY: Gastric biopsy
      specimens were obtained from thirty-seven patients (20 H. pylori-positive and 17
      H. pylori-negative). UDP-galactosyltransferase activity of the biopsy specimens
      was measured by an assay system we had developed, using a peanut agglutinin
      lectin. The amount of intracellular mucin in the gastric epithelial cells was
      analyzed by measuring the cells' periodic acid-Schiff-alcian blue staining
      positive substances. RESULTS: UDP-galactosyltransferase activities in the antral
      mucosa, but not in the body mucosa, of H. pylori-positive patients were
      significantly lower than those of H. pylori-negative patients (p < 0.05). The
      amount of intracellular mucin in antral epithelial cells of H. pylori-positive
      patients was significantly lower than that of H. pylori-negative patients (p <
      0.01). CONCLUSIONS: These findings suggest that H. pylori infection decreases
      gastric mucin synthesis via inhibition of UDP-galactosyltransferase. This effect
      may impair the gastric mucosal barrier and contribute to the mucosal injury
      induced by H. pylori infection.

PMID- 14571834
TI  - [Decomposition from the soil science viewpoint. Soil science principles and
      evaluation. 2].

PMID- 14571833
TI  - [Decomposition from the public health viewpoint with special reference to
      interference with natural biological disintegration processes in burial
      underground. 1].

PMID- 14571835
TI  - [Classification of hereditary spastic paraplegia (HSP)].

PMID- 14571836
TI  - [Pathology of hereditary spastic paraplegia: SPG 11 and related disorders].

PMID- 14571837
TI  - [Recent progress in genetic study of hereditary spastic paraplegia].

PMID- 14571838
TI  - [Hereditary spastic paraplegia associated with thin corpus callosum].

PMID- 14571839
TI  - [Dendritic cell therapy for malignant glioma].
AB  - Despite advances in radiation and chemotherapy along with surgical resectioning,
      the prognosis of patients with malignant glioma is poor. Among the new treatments
      currently being investigated for malignant glioma, immunotherapy is theoretically
      very attractive, since it offers the potential for high tumor-specific
      cytotoxicity. There are increasing reports demonstrating that systemic
      immunotherapy using dendritic cells is capable of inducing an antiglioma
      response. Therefore, dendritic cell-based immunotherapy could be a new treatment
      modality for patients with glioma. Dendritic cell-based immunotherapy strategies
      appear promising as an approach to successfully induce an antitumor immune
      response and increase survival in patients with glioma. The development of
      methods for manipulating dendritic cells for the purpose of vaccination will
      enhance the clinical usefulness of these cells for biotherapy for malignant
      glioma.

PMID- 14571840
TI  - [A case of probable dementia with Lewy bodies presenting with geographic
      mislocation and nurturing syndrome].
AB  - A 83-year-old right handed man developed nurturing syndrome and geographical
      mislocation (misidentification of places) as a result of dementia with Lewy
      bodies. He showed parkinsonism, fluctuating cognition, repeated falls, systematic
      delusions (delusional jealousy with vivid feeling of witness), rapid eye movement
      sleep behavior disorder, and mild dementia. His brain MRI showed atrophy of
      bilateral temporal tips and amygdala. A FDG-PET showed decrease of glucose
      metabolism in right frontal lobe and left temporo-parietal areas. He showed
      constructional disability, frontal lobe dysfunction, mild deterioration of
      immediate memory, mild anterograde amnesia, and retrograde amnesia for recent
      events. Aphasia, apraxia, agnosia, confabulation, or deterioration of facial
      perception was not noted. He could state the genealogy, ages and recent
      whereabouts of his relatives, and could state the locations and geographical
      relationships of his neighboring buildings. He insisted that his father's
      existence, who had died 52 years ago, although he talked about the episode of his
      death just before. One month after having a dream that his sick-room was in a
      fictitious branch of our hospital which located in his neighboring temple, he
      developed a delusion that his ward was actually in the temple. The former
      disorder seems to correspond to the nurturing syndrome described by Venneri et
      al. (2000), and the latter one suggested us that his dream was causally involved
      in the formation of geographical mis-localization. After Ramachandran's
      explanation for Capgras' syndrome, we hypothesized that mis-arousal of
      familiarity evoked by visual perception or memory was attributable to the
      dysfunction of amygdala, and failure of consistency-checking was caused by the
      dysfunction of the right frontal lobe.

PMID- 14571841
TI  - [Systemic lupus erythematosus manifesting as subarachnoid hemorrhage induced by
      cortical venous thrombosis and followed by medial medullary infarction].
AB  - A 43-year-old female, who had been treated for systemic lupus erythematosus
      (SLE), presented with a subarachnoid hemorrhage (SAH) induced by rupture of
      cortical venous thrombosis, and be followed by medial medullary infarction during
      the acute stage of the SAH. The patient initially manifested a SAH. Angiography
      demonstrated no evidence of any aneurysms or arteriovenous malformations, but
      revealed cortical venous thrombosis. She suddenly developed left hemiplegia
      caused by medial medullary infarction on the 6th day. An active anticoagulant
      therapy was thought to be inappropriate because of initial symptoms as a
      hemorrhage. Since she had been accompanied by the medullary infarction, then,
      initially started by antiplatelet therapy. After the confirmation of no saccular
      or dissecting aneurysms with 2nd angiography, her treatment could be changed to
      anticoagulant therapy. Because of the sustained negative reactions of anti
      cardiolipin beta 2 glycoprotein I antibody and lupus anticoagulant during the
      course of SLE, the definite diagnosis of antiphospholipid syndrome (APS) could
      not be made. However, this case is pathogenically thought to be cerebrovascular
      disease based upon APS, considering that this syndrome may be related to various
      antigen/antibody systems.

PMID- 14571842
TI  - [Shrinkage of carotid plaque in a patient with transient ischemic attack].
AB  - A 65-year-old man visited to our hospital, because he felt dull pain on the right
      side of the neck and had transient weakness of the left hand repeatedly. Carotid
      ultrasonography revealed a large plaque with severe stenosis and ulceration at
      the bifurcation of right common carotid artery. The plaque was mostly hypoechoic
      and only the basal part was hyperechoic. Magnetic resonance (MR) study showed
      multiple high-intensity spots in superficial borderzone area of the right
      cerebral hemisphere on fluid attenuated inversion recovery images, although
      diffusion-weighted images revealed no abnormality. Intracranial stenotic lesion
      was not detected by MR angiography. We diagnosed transient ischemic attacks due
      to right carotid artery stenosis. Nine days after the symptom onset, he showed no
      signs of cerebral ischemic attacks and seven days later he began taking aspirin
      and remained stable. Three months later, carotid ultrasonography showed marked
      shrinkage of the carotid plaque, of which hypoechoic part virtually disappeared.
      Release of the atheroma gruel and/or intraplaque hemorrhage due to plaque rupture
      might lead to dramatic change of the carotid plaque.

PMID- 14571843
TI  - [Spontaneous intracranial hypotension manifesting as sudden deafness followed by
      chronic subdural hematoma].
AB  - We report a case of spontaneous intracranial hypotension (SIH) manifesting as
      sudden deafness followed by chronic subdural hematoma in the course of the
      disease. The patient was a 31-year-old female presenting with an orthostatic
      headache. Judging from her characteristic symptoms, SIH was strongly suggested.
      MR images with gadolinium were consistent with the diagnosis of SIH with a
      diffuse dural enhancement. Her symptoms improved gradually by conservative
      therapies with bed rest and oral steroid, but she developed poor hearing at 3
      weeks after the onset of the symptoms. She was diagnosed as having sudden
      deafness. After altering the therapeutic modality to intravenous steroid
      administration, her perceptive deafness resolved earlier, and her symptoms of
      headache disappeared. However, she was readmitted to our hospital at 4 months
      after the onset, complaining of the aggravation of headache with a different
      type, which was worse in the recumbent posture. Follow-up MR images revealed a
      development of subdural hematoma with mass effect, and the hematoma had to be
      treated by burr hole drainage. In this case, the site of CSF leakage along the
      spinal axis was not identified by spinal MR images. This case is considered to be
      a rare one, complicating sudden deafness followed by chronic subdural hematoma
      during the clinical course of the SIH.

PMID- 14571844
TI  - [Diffusion-weighted MRI changes in early stage of Creutzfeldt-Jakob disease].

PMID- 14571845
TI  - [Microhemorrhage of Wernicke encephalopathy detected by T2*-weighted MR image].

PMID- 14571846
TI  - [An autopsy case of degenerative disease characterized by parkinsonism, dementia,
      and pathology with difficulty to be categorized].

PMID- 14571847
TI  - The ruthless malady: metabolic syndrome.

PMID- 14571848
TI  - Take pride in SAFEty: a comprehensive lab-safety program.

PMID- 14571849
TI  - Dealing with a difficult supervisor.

PMID- 14571850
TI  - Develop a useful donor-screening process.

PMID- 14571851
TI  - Testing, 1, 2, 3, testing ... with Quest Diagnostics' Dr. Surya N. Mohapatra.
      Interview by Dottie Durham.

PMID- 14571853
TI  - Where have all the lab workers gone?

PMID- 14571852
TI  - Remote diagnostics monitors vital signs in the lab.

PMID- 14571854
TI  - Power: do women really want it.

PMID- 14571855
TI  - Family ties.

PMID- 14571856
TI  - If you're losing patients to specialists....

PMID- 14571857
TI  - Frivolous suits. These doctors bite back.

PMID- 14571858
TI  - Your rights if the feds come knocking.

PMID- 14571859
TI  - Physicians' earnings. Our exclusive survey.

PMID- 14571860
TI  - Enlist patients in error prevention.

PMID- 14571861
TI  - Liability when a doc is part-time.

PMID- 14571862
TI  - We're at the breaking point.

PMID- 14571863
TI  - The usefulness of F-18 deoxyglucose whole-body positron emission tomography (PET)
      for re-staging of renal cell cancer.

PMID- 14571864
TI  - Home care nurses urged to champion prevention.

PMID- 14571875
TI  - Identification and characterization of trypsin, chymotrypsin and elastase
      inhibitors in the hedgehog, Erinaceus europaeus, and their immunological
      relationships to those of other mammals (rat, pig and human).
AB  - 1. Hedgehog plasma was separated by gel filtration on Sephacryl S-200, the
      fractions resolved by electrophoresis and the electrophoregrams characterized for
      trypsin, chymotrypsin and elastase inhibiting activities with both low and high
      molecular weight substrates. Approximate molecular weights were also determined.
      2. At least ten protease inhibitors were characterized in hedgehog plasma
      including three macroglobulins. 3. The hedgehog protease inhibitors were
      identified by immunoelectrophoresis. Four protease inhibitors showed homologies
      with specific human, rat or swine antisera. These were alpha 2-and beta
      macroglobulins, alpha 1-protease inhibitor, and alpha 2-antithrombin.

PMID- 14571876
TI  - Following the guideline for pain control in the elderly.

PMID- 14571877
TI  - Removing sutures and staples.

PMID- 14571878
TI  - Reducing the risk of rabies.

PMID- 14571879
TI  - How dental status affects healing in older adults.

PMID- 14571880
TI  - Urea tolerance and osmoregulation in Bufo viridis and Rana ridibunda.
AB  - 1. The tolerance and adaptation to urea solutions by terrestrial green toads
      (Bufo viridis) and semi-aquatic frogs (Rana Ridibunda) were studied. 2. the green
      toad showed tolerance to urea solution of 800 mM and the frogs showed tolerance
      only to about 400 mM urea solution. 3. The plasma concentrations of both species
      was hyperosmotic to the external medium in all the different urea solutions. 4.
      Blood osmolality, urea, Na+ and Cl- concentrations of B. viridis were always
      higher than in R. ridibunda. 5. The urea concentration in muscle of R. ridibunda
      was higher than the urea concentration in muscle of B. viridis. 6. The muscle
      tissue weight loss of B. viridis was significantly lower than R. ridibunda.

PMID- 14571884
TI  - Revival of biochemistry in Poland in the first years after World War II.

PMID- 14571885
TI  - Reducing risks from combative patients.

PMID- 14571886
TI  - The birth of biochemistry in Lodz.

PMID- 14571887
TI  - Post-war biochemistry in Wroclaw.

PMID- 14571888
TI  - Why is this patient lethargic?

PMID- 14571889
TI  - The initial period of biochemistry in Lublin.

PMID- 14571890
TI  - The beginning of scientific research in biochemistry in Gdansk after the end of
      World War II.

PMID- 14571894
TI  - Reminiscences.

PMID- 14571897
TI  - Recollections of 1939-1949: from Politechnika Lwowska to Politechnika Gdanska.

PMID- 14571899
TI  - Respiratory metabolism of D[U-14C]glucose in hens and cocks during prolonged
      treadmill exercise.
AB  - 1. The specific activity of expired 14CO2 was measured at rest and during 90 min
      treadmill exercise following an initial intravenous injection of D[U-14C]glucose.
      2. The rate of CO2 production rose 4.5-fold during exercise in cocks but only 2.5
      fold in females. The mean respiratory quotient was close to unity at rest and
      during exercise. 3. Estimated glucose turnover rate rose approximately 3.5-fold
      during exercise in cocks. Turnover rate did not increase in hens but the fraction
      of the glucose turnover oxidized to provide energy for the working muscles was
      increased. 4. It is concluded that carbohydrate sources account for the major
      fraction of energy expenditure during exercise of this magnitude and duration.

PMID- 14571900
TI  - [Postoperative radiologic evaluation in uroradiology. Part 2: Bladder, prostate,
      and testis].
AB  - Radiologists, especially uroradiologists, must retain abreast of rapid
      developments in urologic therapy and operative techniques in order to critically
      assess postoperative changes. Part 2 of this review will cover therapy and
      postoperative evaluation in bladder surgery, surgery in prostate cancer, and
      retroperitoneal disease associated with testicular tumors. Using the appropriate
      modality at the appropriate time during the postoperative course is discussed. A
      variety of alternatives are available to perform urinary diversion after radical
      cystectomy. Knowledge of operative techniques and postoperative anatomy are
      mandatory for interpretation of postoperative radiologic findings.

PMID- 14571903
TI  - Handling documentation errors.

PMID- 14571906
TI  - [Cardiac pacemaker registry. German Central Cardiac Pacemaker Registry. Annual
      report, 2000/2001].

PMID- 14571907
TI  - [DRG exercises: vacuum sealing, tibial fracture with compartment syndrome].

PMID- 14571908
TI  - [GOA--Settlement on hip joint surgery. Principle of payment limit. Decision of
      the Karlsruhe District Court of 3/28/2003-1 S 106.02].

PMID- 14571909
TI  - [Corruption and indirect means].

PMID- 14571910
TI  - [Is medical ethos generally still expected?].

PMID- 14571911
TI  - [Protocol of the Main Annual Conference, 2003, of the LV Brandenburg in BDC].

PMID- 14571912
TI  - [Finally, peace has to rule in the operating room. Economic pressures encourage
      the partnership between anesthetists and surgeons].

PMID- 14571913
TI  - [Lung biopsy: indication and choice of procedure. Synopsis from Chirurg, Issue
      8/2003].

PMID- 14571914
TI  - An antegrade endopyelotomy in a 77-year-old man for a strictured ureteropelvic
      junction secondary to stone disease.

PMID- 14571915
TI  - Comment on "Four analgesic techniques for shockwave lithotripsy: eutectic mixture
      local anesthetic is a good alternative".

PMID- 14571916
TI  - Dual X-ray absorptiometry of hip, heel ultrasound, and densitometry of fingers
      can discriminate male patients with hip fracture from control subjects: a
      comparison of four different methods.

PMID- 14571917
TI  - 'Benign convulsions with mild gastroenteritis'--a worldwide clinical entity.

PMID- 14571918
TI  - A medical menu.

PMID- 14571919
TI  - [Comment on the article "The harmonic scalpel and surgery of the thyroid gland"
      by B. Vach, J. Fanta and Z. Velenska].

PMID- 14571920
TI  - [The doctor and medical officer of health, Friedrich Wilhelm von Hoven (1759
      1838): his life, work, and friendship with Friedrich Schiller].

PMID- 14571921
TI  - [References and aids in parenchyma preserving surgery of kidney tumors].

PMID- 14571922
TI  - [Child abuse in France: how much, how reliable are the numbers?].

PMID- 14571923
TI  - [Legal permission for satellite and distant medical offices].

PMID- 14571924
TI  - Periapical actinomycosis.

PMID- 14571925
TI  - The lighthouse at Coxsackie, New York.

PMID- 14571926
TI  - Hormone replacement therapy and bias.

PMID- 14571927
TI  - Palatal implants and parental response.

PMID- 14571928
TI  - Space closure for a missing central incisor.

PMID- 14571929
TI  - Space closure for a second premolar.

PMID- 14571930
TI  - Crown dimensions and the alignment or crowding of mandibular incisors.

PMID- 14571931
TI  - Raising the public profile of lung cancer--report of a National Lung Cancer
      Awareness campaign in the UK.

PMID- 14571932
TI  - Pseudotumour cerebri as an unusual manifestation of typhoid.

PMID- 14571933
TI  - Cancrum oris and acute necrotising gingivitis complicating HIV infection in
      children.

PMID- 14571934
TI  - Necrotising fasciitis of the perineum complicating ischiorectal abscess in
      childhood.

PMID- 14571935
TI  - Bacterial isolates and antimicrobial sensitivity patterns in a tertiary level
      neonatal unit environment in a developing country.

PMID- 14571936
TI  - Trauma care systems in New Zealand.
AB  - Trauma in New Zealand is modest in extent in relation to many other areas of the
      world. Trauma care is delivered in the context of an ad hoc trauma system which
      nevertheless seems to function reasonably well. Current funding strictures in the
      short term seem likely to prevent formal adoption of a trauma system which would
      have the prospect of providing information determining the real quality of trauma
      care in New Zealand.

PMID- 14571937
TI  - Evaluation of a new desktop spirometer: problem with statistical methods used.

PMID- 14571938
TI  - Alignment of trans-tibial prostheses based on roll-over shape principles.
AB  - The authors examined the roll-over shape alignment hypothesis, which states that
      prosthetic feet are aligned by matching their roll-over shapes with an "ideal"
      shape. The "ideal" shape was considered to be the roll-over shape of the able
      bodied foot-ankle system. An alignment algorithm and computational alignment
      system were developed to set trans-tibial alignments based on this hypothesis.
      Three prosthetic feet with considerably different roll-over shapes were either
      aligned using the alignment system or not aligned (i.e. used previous foot's
      alignment), and then were aligned by a team of prosthetists. No significant
      differences were found between roll-over shapes aligned by the computational
      alignment system and those based on standard clinical techniques (p = 0.944).
      Significant differences were found between the "no alignment" shapes and the
      prosthetist alignment shapes (p = 0.006), and between the "no alignment" shapes
      and the computational alignment system shapes (p = 0.024). The results of the
      experiment support the hypothesis that the goal of alignment is to match the
      prosthetic foot's roll-over shape, as closely as possible, with an "ideal" shape.
      The hypothesis is also supported by its ability to explain the results of
      previous studies. Using an "ideal" roll-over shape or surface as a goal for
      prosthetic alignment could lead to a priori alignment, eliminating the need for
      alignment hardware in some cases. Being able to build the alignment into a
      prosthesis without special hardware could be beneficial in low-income countries
      and in the fabrication of lightweight prostheses for the elderly.

PMID- 14571939
TI  - Pilot study: data-capturing consistency of two trans-tibial casting concepts,
      using a manikin stump model: a comparison between the hands-on PTB and hands-off
      ICECAST compact concepts.
AB  - The quality of fit of a trans-tibial patellar tendon bearing (PTB) socket may be
      influenced by consistency in casting, rectification or alignment. For this study
      two distinctive different data-capturing concepts were tested in relation to
      prosthetist performance. The hands-on PTB and hands-off ICECAST compact concept
      were studied and compared for inter- and intra-prosthetist consistency using a
      specially designed manikin stump model. A purpose designed digitiser was used to
      scan a selected surface area of the produced models, 5 for each concept, 10 in
      total. The extent of casting consistency at each of 936 locations per plaster
      model was calculated and the level of consistency was quantified. This study has
      shown that by using the manikin model there is a clear indication that the
      investigated hands-off concept produces more consistent results than the hands-on
      concept.

PMID- 14571940
TI  - Walking in a vacuum-assisted socket shifts the stump fluid balance.
AB  - Gains in stump volume have been documented in trans-tibial amputees while walking
      in custom made under-sized, total surface-bearing, vacuum-assisted sockets (Board
      et al., 2001). These gains raised doubts as to whether the sockets were truly
      under-sized and concerns that using an over-sized socket with vacuum-assist could
      lead to swelling, resulting, in discomfort or pain. The purposes of the present
      study were to determine if: (a) walking in a vacuum-assisted socket causes the
      stump to retain or gain volume in excess of the available socket volume and (b)
      the resulting increase in stump volume with an over-sized socket causes
      discomfort, pain, and/or the skin to redden. The results of this study showed the
      stump retained or gained volume in excess of the available socket volume while
      walking in vacuum-assisted sockets of various sizes. The stump lost less volume
      than predicted, or gained volume, in under-sized sockets. It also gained more
      volume than predicted in over-sized sockets. No discomfort, pain, or skin
      reddening, resulting from the volume gain was reported by any of the subjects
      after walking in an over-sized socket. This change in fluid balance towards a net
      gain supports the findings by Board et al. (2001) that vacuum-assist ensures a
      good fit during the day in ambulatory trans-tibial traumatic amputees with mature
      stumps.

PMID- 14571941
TI  - Rehabilitation of the trans-femoral amputee with an osseointegrated prosthesis:
      the United Kingdom experience.
AB  - Osseointegration for the trans-femoral amputee has been used in the United
      Kingdom since 1997. To date, 11 candidates have undergone the procedure. The
      rehabilitation programme for the osseointegration candidate is a long and
      intensive programme following two surgical operations. This paper outlines the
      importance of a pre-osseointegration assessment to explore candidates'
      suitability and expectations for the procedure. The physical and prosthetic
      advantages of direct skeletal attachment have led to improvements in candidates'
      comfort, function and quality of life. However, some aspects of this promising
      developmental procedure for the management of the trans-femoral amputee need to
      be critically evaluated before it becomes a routine clinical procedure in the
      United Kingdom.

PMID- 14571942
TI  - Effect of different casting methods on adolescent idiopathic scoliosis.
AB  - Scoliosis is a three-dimensional spinal deformity. Although orthotic treatment
      for moderate adolescent idiopathic scoliosis (AIS) has been well recognized,
      there are few studies documenting the effectiveness of different casting methods
      in the fabrication of thoracolumbo-sacral orthoses (TLSO). The current study was
      a retrospective clinical evaluation of the effectiveness of two commonly used
      casting methods namely, the frame casting method and the supine with traction
      casting method in the treatment of AIS. Eighty (80) female patients with AIS were
      recruited and they were all treated by TLSOs. The frame casting method was used
      in 37 patients while the remaining 43 patients were under the supine with
      traction casting method. The responses of spinal deformities under the two
      different casting methods were analyzed for the period from pre-brace to 2 years
      after bracing. The studied parameters included the AP Cobb's angle, the apical
      vertebral rotation and the trunk listing (cervico-sacral lateral offset). The
      results of the current study showed that the orthoses manufactured from the two
      casting methods could provide an effective control of AIS (change of Cobb's angle
      within (+/- 5 degrees). For the frame casting, the Cobb's angles at pre-brace and
      2 years after off-brace were 36.0 degrees and 33.8 degrees respectively while for
      the supine with traction casting, the corresponding Cobb's angles were 32.7
      degrees and 34.0 degrees. The frame casting method could give a better control of
      the apical vertebral rotation at the early stage of treatment (pre-brace = 18.2
      degrees and the 4th month = 13.8 degrees while the supine with traction casting
      method was more effective in the long-term control of the trunk listing (pre
      brace = 10mm and 2 years after off-brace = 3.3mm).

PMID- 14571943
TI  - New technical advances in swivel walkers.
AB  - Swivel walkers were commonly prescribed for children with complete thoracic
      lesion myelomeningocele in the 1970s and 80s, when the incidence of spina bifida
      in the UK was of the order of 3 per 100,000 live births. The advent of reciprocal
      walking orthoses provided a more suitable alternative for those with good upper
      limb and trunk function, and swivel walkers were then used primarily for very
      young or more severely disabled patients. Pre-natal screening has dramatically
      reduced the incidence of spina bifida in the UK and subsequently swivel walkers
      have been used in a wider range of pathology, including spinal muscular atrophy,
      multiple sclerosis, muscular dystrophy and other neurological conditions that
      lead to lower limb dysfunction. The detail design of these devices has been
      adapted to accommodate the specific problems encountered in these conditions. In
      particular the designs have been updated to: enable very young patients to be
      more readily fitted at the age of 1 year; allow the walking mechanisms to be
      conveniently adjusted for easier ambulation when weakness or lack of confidence
      inhibits performance; permit simple adjustment to a standing frame mode to
      enhance stability in situations of increased risk; promote manual handling
      practice that is compatible with the National Health Service (NHS) policy of
      compliance with relevant regulations. To underpin appropriate prescription and
      safe supply the NHS Procurement Agency have encouraged the development of a
      common course for all types of swivel walker.

PMID- 14571944
TI  - Splint satisfaction in the treatment of traumatic radial nerve injuries.
AB  - Between the years 1986-2001, 135 patients who have had traumatic radial nerve
      injury, were supplied with dynamic wrist-hand orthoses (WHOs). The aim of this
      study is to examine the applied splints, considering aspects such as apperance,
      practicality of use, function, comfort and endurance. The author's assessments
      show that the biggest problem was due to the unaesthetic appearance of the finger
      extensor spring of the splints. For this reason, modification of these finger
      extensor outriggers has been attempted. Also, aspects of the splints such as the
      problems faced and regeneration of the nerve, have been considered and
      modifications made in order to eliminate any disfunction. This study reflects the
      reactions and satisfaction of 83 patients concerning the splints they have used.
      Conventional wire springs have been used in the splints of 71 patients, and 12
      had modifications done on their outriggers. In terms of appearance, there were
      significant differences between modified outriggers and conventional outrigger (p
      < 0.05). Also, when the modified outriggers were compared in terms of appearance
      and durability, there was a statistically significant opinion in favour of them
      (p < 0.01).

PMID- 14571945
TI  - CIR sand casting system for trans-tibial socket.
AB  - The authors have developed a trans-tibial socket fabrication system based on the
      "dilatancy" principle, a process that has been commonly used in forming
      wheelchair Seating. The CIR Sand Casting System replaces plaster of Paris with
      sand for forming both a negative sand mould and a positive sand model, which can
      be modified for either thermoplastic socket formation or resin lamination.
      Initial clinical trials suggest that fabrication times are approximately 90
      minutes from patient evaluation and casting to dynamic alignment. Compatibility
      with all existing prosthetic components is retained. It is believed the CIR
      socket fabrication system may be a competitive alternative for prosthetic service
      providers in developing countries.

PMID- 14571946
TI  - Lengthening of short stumps for functional use of prostheses.
AB  - The length of a stump plays an important role when using a prosthesis. It is
      essential to have an adequate length in the stump in order to apply the
      prosthesis. Therefore, it is necessary to attempt to lengthen short stumps. The
      authors have reviewed the results in 2 patients who had such lengthening of
      stumps one due to traumatic amputation of the forearm at 6.25 cm distally from
      the elbow and the other due to congenital deficiency of the radius and ulna
      treated by the Ilizarov techinque to improve the fitting of prostheses. Sixty
      percent (60%) and 40% lengthening was achieved respectively. At the end of the
      lengthening process, sufficient stump length for the prosthesis was achieved.
      There were no major complications. As a result, it is believed stump lengthening
      is a valuable method for cosmetic and functional use of the prosthesis. The
      Ilizarov Technique is an effective method of lengthening of a stump and it does
      not require a tissue expander in selected patients. Patients have been able to
      use their prosthesis 6 months after surgery.

PMID- 14571947
TI  - CAREN (computer assisted rehabilitation environment): a novel way to improve shoe
      efficacy.
AB  - A new technical system, CAREN (computer assisted rehabilitation environment), is
      described, which makes it possible to do a total body movement analysis in a
      virtual environment. The virtual environment is reproducible and as close to
      natural environment as possible. In a case study it proved possible with this
      system to test different shoes and get insight in the movement problems. The
      importance of whole body analysis is demonstrated in this case study. The
      adjustments made in the shoes could be tested for their efficacy.

PMID- 14571948
TI  - TNT biotransformation and detoxification by a Pseudomonas aeruginosa strain.
AB  - Successful microbial-mediated remediation requires transformation pathways that
      maximize metabolism and minimize the accumulation of toxic products. Pseudomonas
      aeruginosa strain MX, isolated from munitions-contaminated soil, degraded 100 mg
      TNT L(-1) in culture medium within 10 h under aerobic conditions. The major TNT
      products were 2-amino-4,6-dinitrotoluene (2ADNT, primarily in the supernatant)
      and 2,2'-azoxytoluene (2,2'AZT, primarily in the cell fraction), which
      accumulated as major products via the intermediate 2-hydroxylamino-4,6
      dinitrotoluene (2HADNT). The 2HADNT and 2,2'AZT were relatively less toxic to the
      strain than TNT and 2ADNT. Aminodinitrotoluene (ADNT) production increased when
      yeast extract was added to the medium. While TNT transformation rate was not
      affected by pH, more HADNTs accumulated at pH 5.0 than at pH 8.0 and AZTs did not
      accumulate at the lower pH. The appearance of 2,6-diamino-4-nitrotoluene
      (2,6DANT) and 2,4-diamino-6-nitrotoluene (2,4DANT); dinitrotoluene (DNT) and
      nitrotoluene (NT); and 3,5-dinitroaniline (3,5DNA) indicated various routes of
      TNT metabolism and detoxification by P. aeruginosa strain MX.

PMID- 14571949
TI  - Naphthalene and anthracene mineralization linked to oxygen, nitrate, Fe(III) and
      sulphate reduction in a mixed microbial population.
AB  - A microbial consortium from a mixture of garden soil and an enrichment of a coal
      tar contaminated sediment mineralized naphthalene and anthracene when oxygen,
      nitrate, Fe(III) (soluble and insoluble) or sulphate were provided as terminal
      electron acceptors (TEAs). Rates of polyaromatic hydrocarbon disappearance and
      mineralization were similar in the presence of oxygen and nitrate, and slower
      with the other TEAs. A maximum mineralization of 37.5% naphthalene and 8.5%
      anthracene occurred in 30 and 160 days respectively when oxygen was provided as
      the TEA. On the other hand, only 9.5% naphthalene and 3.2% anthracene were
      mineralized in 42 and 160 days respectively with FeOOH. Mineralization occurred
      only when a TEA was provided and ceased when the naphthalene concentration
      decreased to non-detectable levels (less than 0.008 micromoles/L), as measured by
      fluorescence spectroscopy. CH4 was not detected in the headspace of any
      microcosm. These results showed that mineralization of polyaromatic hydrocarbons
      such as naphthalene and anthracene can be linked to wide range of TEAs
      demonstrating that intrinsic polyaromatic hydrocarbon bioremediation is possible
      if any of these TEAs were available.

PMID- 14571950
TI  - Predicting biogeochemical calcium precipitation in landfill leachate collection
      systems.
AB  - Clogging of leachate collection systems within municipal solid waste landfills
      can result in greater potential for contaminants to breach the landfill barrier
      system. The primary cause of clogging is calcium carbonate (CaCO3(s))
      precipitation from leachate and its accumulation within the pore space of the
      drainage medium. CaCO3(s) precipitation is caused by the anaerobic fermentation
      of volatile fatty acids (VFAs), which adds carbonate to and raises the pH of the
      leachate. An important relationship in modeling clogging in leachate collections
      systems is a yield coefficient that relates microbial fermentation of VFAs to
      precipitation of calcium carbonate. This paper develops a new, mechanistically
      based yield coefficient, called the carbonic acid yield coefficient (Y(H)), which
      relates the carbonic acid (H2CO3) produced from microbial fermentation of
      acetate, propionate, and butyrate to calcium precipitation. The empirical values
      of Y(H) were computed from the changes in acetate, propionate, butyrate, and
      calcium concentrations in leachate as it permeated through gravel-size material.
      The theoretical and empirical results show that the primary driver of CaCO3(s)
      precipitation is acetate fermentation. Additionally, other non-calcium cations
      (e.g., iron and magnesium) precipitated with carbonate (CO3(2-)) when present in
      the leachate. A common yield between total cations bound to CO3(2-) and H2CO3
      produced, called the calcium carbonate yield coefficient (Yc), can reconcile the
      empirical yield coefficient for synthetic and actual leachates.

PMID- 14571952
TI  - Biodegradation of 2-chlorobenzoate by recombinant Burkholderia cepacia expressing
      Vitreoscilla hemoglobin under variable levels of oxygen availability.
AB  - The influence of bacterial hemoglobin, VHb, on dechlorination and degradation of
      2-chlorobenzoate (2-CBA) by recombinant Burkholderia sp. under variable oxygen
      availability with an initial dissolved oxygen concentration of 0.27 mM-0.72 mM
      was investigated in batch and continuous culture. Ability to express VHb was
      provided to recombinant Burkholderia by transformation with the VHb gene, vgb, on
      plasmid pSC160. 100% of 0.5 mM CBA was degraded in cultures with 85% and 70% of
      total volume as headspace air in closed reactors by both wild type and
      recombinant Burkholderia. The recombinant cultures were able to dechlorinate and
      degrade 100% of the 2-CBA in less than 48 hours at 30 degrees C compared to more
      than 120 hours for wild type cultures. The rate and extent of CBA degradation by
      recombinant cultures with 40% of total volume as headspace air was higher than
      those achieved by wild type cells at the end of the 168 hours of incubation
      period, 98 and 73%, respectively. The chloride released: CBA degraded molar ratio
      for cultures with 40% of total volume headspace air was nearly stoichiometric
      (molar ratio = 1.0) for recombinant strains, whereas it was non-stoichiometric
      (molar ratio = 0.24) for wild type cells. The results suggest a suicidal meta
      pathway for wild type cells and a complete dechlorination and degradation pathway
      for recombinant cells under hypoxic conditions. The degradation and
      dechlorination ability of both types of cells was also investigated in continuous
      reactor studies by varying the dilution rate under hypoxic conditions. Regarding
      potential of the recombinant strain for 2-CBA degradation in either open
      ecosystems or closed bioreactor bioremediation systems, the stability of the
      plasmid containing vgb in the recombinant cells was also studied; the plasmid was
      100% stable at 0.025 h(-1) dilution rate (approximately 1.7 d hydraulic retention
      time), even after one month.

PMID- 14571951
TI  - Effective bead preparation of coimmobilized methanogenic and methanotrophic
      bacteria for tetrachloroethene degradation.
AB  - Three types of coimmobilized methanogenic and methanotrophic bacterial beads--Ca
      alginate, Ba-alginate, and Ca-alginate chitosan--were used for tetrachloroethene
      (PCE) degradation. For the purpose of effective preparation of coimmobilized
      bacterial beads, the diameter and broken-loading of beads were measured. The
      activity tests to find the optimal bacteria concentration in the bead were
      performed. It was found that Ba-alginate beads had superiority in bacterial
      growth and the degree of strength of beads from the diameter and broken-loading
      tests. Also, it was shown that it is most effective to add 200 mL of methanogens
      into 500 mL of 2% alginate solution and 20 mL of methanotrophs into 500 mL to 2%
      alginate solution. When methanogens and methanotrophs were applied with the Ba
      alginate bead in the actual dechlorination of PCE, the biological PCE
      dechlorination rate was 92%, and there was highly effective degradation of PCE
      based on the coimmobilized bead. Additionally, relation to the diameter (X) and
      broken-loading (Y) of the Ba-alginate bead was derived following equation, Y =
      438.02 exp(-1.4815 X).

PMID- 14571953
TI  - Applied exercise physiology: a personal perspective of the past, present, and
      future.

PMID- 14571954
TI  - Growth hormone molecular heterogeneity and exercise.
AB  - There are more than 100 molecular isoforms of circulating growth hormone (GH),
      but the traditional measurement approach in the exercise literature has only
      focused on the main isoform (i.e., 22 kDa). New assay methodologies now can
      assess various GH isoforms. The current data suggest that exercise results in the
      preferential release of GH isoforms with extended half-lives, thereby sustaining
      biological actions.

PMID- 14571955
TI  - Muscular force transmission necessitates a multilevel integrative approach to the
      analysis of function of skeletal muscle.
AB  - Muscular force is transmitted not only to tendon but also to other structures.
      Connections to extramuscular connective tissue of a compartment and to other
      muscles are stiff enough to transmit force. The concept of myofascial force
      transmission is reviewed and some functional consequences considered. An approach
      for analysis is suggested.

PMID- 14571956
TI  - Physical activity and cardiovascular disease prevention in women: how much is
      good enough?
AB  - Epidemiologic data suggest that 30 min x d(-1) of brisk walking can reduce
      cardiovascular disease incidence in women and men. In a sedentary society, public
      health initiatives that promote moderate increases in physical activity may
      represent the optimal balance between efficacy, feasibility, and safety to
      achieve the desired cardioprotective effect.

PMID- 14571957
TI  - Lateral stability and falls in older people.
AB  - Aging changes in specific neuromusculoskeletal factors affecting protective
      stepping and other balance functions may precipitate lateral instability and
      falls. Identification of these factors provides directives for novel therapeutic
      interventions to reduce fall risk in older people.

PMID- 14571958
TI  - Experimental animal models of muscle pain and analgesia.
AB  - Muscle pain is a prevalent clinical problem but can be difficult to treat because
      relatively little is known about nervous system mechanisms that mediate and
      modulate it. This review profiles four new animal models of muscle and deep
      tissue pain currently being used to elucidate mechanisms of muscle pain and
      analgesia.

PMID- 14571959
TI  - Dynamic knee stability after anterior cruciate ligament rupture.
AB  - A functional classification scheme has been devised to study knee stabilization
      strategies after anterior cruciate ligament rupture. A screening examination can
      determine which patients may be candidates for nonsurgical treatment (potential
      copers). A rehabilitation program that includes support surface perturbations can
      improve the potential coper's ability to stabilize the knee. Biomechanical,
      electromyographic, and clinical data support the classification scheme and
      perturbation training for improving dynamic knee stability.

PMID- 14571960
TI  - Uncertainty and the scientist.

PMID- 14571961
TI  - Coping with uncertainty: a call for a new science-policy forum.
AB  - The scientific and policy worlds have different goals, which can lead to
      different standards for what constitutes "proof" of a change or phenomena, and
      different approaches for characterizing and conveying uncertainty and risk. These
      differences can compromise effective communication among scientists,
      policymakers, and the public, and constrain the types of socially compelling
      questions scientists are willing to address. In this paper, we review a set of
      approaches for dealing with uncertainty, and illustrate some of the errors that
      arise when science and policy fail to coordinate correctly. We offer a set of
      recommendations, including restructuring of science curricula and establishment
      of science-policy forums populated by leaders in both arenas, and specifically
      constituted to address problems of uncertainty.

PMID- 14571962
TI  - Biogeochemistry of mercury in the Amazonian environment.
AB  - In this paper, the processes that affect mercury (Hg) cycling in the Amazonian
      environment were reviewed, criticized and new directions of research are
      proposed. The discussion of the origin of the mercury contamination, whether
      natural or anthropogenic is marked by a lack of fundamented arguments from both
      sides. Undoubtedly mercury inputs from gold mining have locally increased
      environmental concentrations, but in the whole Amazon, these loads would be
      insignificant, considering the high concentrations observed by some authors in
      remote soils. A reasonable process that should explain these elevated
      concentrations in soil is that B horizons function as a mercury "sponge" that
      have been accumulating mercury over a geological time scale, releasing it back to
      cycling during erosion and forest fires. The environmental degradation of the
      Amazonian forest due to human activities is probably enhancing the release of
      that mercury to the cycle. Mercury transformations in reduced, anoxic
      environments--sediments and waters--are also a key problem for the understanding
      of the environmental methylation. The studies that have been carried out in the
      Amazonian environment are too restricted and results permit only circumstantial
      conclusions. Large efforts must be directed to monitoring programs considering
      time and space variability.

PMID- 14571963
TI  - Deforestation control in Mato Grosso: a new model for slowing the loss of
      Brazil's Amazon forest.
AB  - Controlling deforestation in Brazil's Amazon region has long been illusive
      despite repeated efforts of government authorities to slow the process. From 1997
      to 2000, deforestation rates in Brazil's 9-state "Legal Amazon" region
      continually crept upward. Now, a licensing and enforcement program for clearing
      by large farmers and ranchers in the state of Mato Grosso appears to be having an
      effect. The deforestation rate in Mato Grosso was already beginning to slacken
      before initiation of the program in 1999, but examination of county-level data
      suggests that deforestation in already heavily cleared areas was falling due to
      lack of suitable uncleared land, while little-cleared areas were experiencing
      rapid deforestation. Following initiation of the program, the clearing rates
      declined in the recent frontiers. Areas with greater enforcement effort also
      appear to have experienced greater declines. Demonstration of government ability
      to enforce regulations and influence trends is important to domestic and
      international debates regarding use of avoided deforestation to mitigate global
      warming.

PMID- 14571964
TI  - Rainforest composition and histories of human disturbance in Solomon Islands.
AB  - On the basis of a Solomon Islands case study, we report that tropical rainforests
      hitherto perceived as untouched, pristine, virgin, etc., are actually sites of
      former settlement, extensive forest clearance, and irrigated/swidden agriculture.
      An unusually wide range of sources--rainforest ecology, forest classification and
      mapping, ethnobotany, land-use history, oral traditions, ethnographic and
      archaeological observations--supports our conclusions. These observations have
      bearings for contemporary perspectives on scenarios for rainforest regeneration
      after logging. They also force a revision of certain assumptions concerning
      Melanesian prehistory and historical demography, and indicate that
      interdisciplinary links between botany, archaeology and social anthropology are
      needed to achieve a better appreciation of rainforest dynamics.

PMID- 14571965
TI  - Valuing coral reefs: a travel cost analysis of the Great Barrier Reef.
AB  - This study examines domestic and international travel to the Great Barrier Reef
      in order to estimate the benefits the reef provides to the 2 million visitors
      each year. The study explores the problems of functional form and of measuring
      travel cost for international visits: comparing actual costs, distance, and
      lowest price fares. The best estimates of the annual recreational benefits of the
      Great Barrier Reef range between USD 700 million to 1.6 billion. The domestic
      value to Australia is about USD 400 million, but the estimated value to more
      distant countries depends on the definition of travel cost and the functional
      form. The study conclusively demonstrates that there are very high benefits
      associated with protecting high quality coral reefs.

PMID- 14571966
TI  - Disinfection of septic tank and cesspool wastewater with peracetic acid.
AB  - Wastewaters of private household septic tanks and cesspools have been treated
      with peracetic acid (1-2 g L(-1)). Adding 1 g L(-1) peracetic acid to wastewaters
      was easy and has been found to be effective in destroying enteric indicator
      microorganisms. The careful mixing of peracetic acid and wastewater was found to
      be important. Winter periods with frozen soil, ice and snow did not constitute
      extra problems. The bad smell of these wastewaters almost totally disappeared
      during the treatment. When wastewaters treated with peracetic acid were emptied
      into animal slurry tanks, hygienization still continued in the mixture of animal
      slurry and the wastewaters. These wastewaters could thus be released into
      agricultural soil without risk of microbiological pollution to groundwaters.

PMID- 14571967
TI  - Controlling residential water demand in Qatar: an assessment.
AB  - Qatar has serious water resource problems, following rapid socioeconomic
      development and massive population increase. Municipal water provision depends on
      costly and unsustainable desalination. There is little regulation. Native Qataris
      do not pay a water tariff and migrants pay a subsidized price--approximately one
      third of the cost of production--so there is little awareness of the true cost of
      water and use is profligate. This paper discusses trends in water use and
      identifies issues underlying sustainable water use in Qatar. A questionnaire of
      respondents chosen to represent Qatari social groups measured awareness and
      attitudes to water. The results show that previous efforts to control water
      demand in Qatar, using awareness campaigns, legal restrictions and tariffs, have
      been ineffectual. The questionnaire evaluated reactions to possible measures to
      limit uses by raising awareness, using legal restrictions and raising tariffs.
      From this, a number of policy changes can be suggested, to bring Qatar's water
      industry towards sustainability.

PMID- 14571968
TI  - African land ecology: opportunities and constraints for agricultural development.
AB  - Compared to other continents, the economic growth performance of Sub-Saharan
      Africa has been poor over the last four decades. Likewise, progress in
      agricultural development has been limited and the Green Revolution left Africa
      almost untouched. The question raised in the literature is whether the poor
      performance is a question of poor policies or of an unfavorable biophysical
      environment (policy versus destiny). This paper, with a broad perspective,
      analyzes adaptation of current land use to environmental conditions in Africa and
      compares the physical resource base of Africa with Asia. In doing so, we search
      for unifying principles that can have operational consequences for agricultural
      development. We argue that some specificities of the natural resource base,
      namely local homogeneity and spatial diversity of the predominant Basement
      Complex soils, imply that simple fertilizer strategies may not produce the yield
      increases obtained elsewhere.

PMID- 14571969
TI  - Vanishing seagrass (Zostera marina, L.) in Swedish coastal waters.
AB  - Along the Swedish Skagerrak coast eelgrass (Zostera marina) is a dominant
      phanerogam on shallow soft bottoms. Eelgrass meadows are important biotopes for
      many crustacean and fish species being either migratory or stationary. During the
      1980s, inventories of the shallow coastal areas with eelgrass have been carried
      out along the Swedish west coast as a basis for coastal zone management. In the
      present study we revisited 2000 ha of eelgrass meadows in 5 coastal regions along
      200 km of the Skagerrak coast. The inventory was made with the same methods
      (aquascope) as during the 1980s, but increasing the mapping accuracy by using a
      Global Positioning System (GPS). The results from this study show that the areal
      extension of Zostera marina has decreased 58% in 10-15 years with great regional
      variations. The decline was mainly restricted to the shallow parts of the meadow.
      The causes and ecological consequences are discussed.

PMID- 14571970
TI  - Genetically modified soybeans: false-positive detection in fermented natural
      soybean (tempe).
AB  - Tempe was prepared using mixtures of natural soybean and genetically modified
      Roundup Ready (RUR) soybean fermented with natural Rhizopus sp. The amount of RUR
      soybean was quantified using an ELISA plate test. The RUR signal decreased during
      fermentation. In the control experiments on fermentation of non-RUR soybean, the
      tempe gave a false-positive RUR signal. The cross-reacting substance was
      generated only in non-RUR soybean during fermentation by Rhizopus sp., Rhizopus
      oligosporus, R. oryzae, Mucor rouxii and Aspergillus awamori.

PMID- 14571971
TI  - Disruption of sabR affects nikkomycin biosynthesis and morphogenesis in
      Streptomyces ansochromogenes.
AB  - The gene, sabR, encoding a receptor for gamma-butyrolactone, was cloned from the
      genomic DNA of Streptomyces ansochromogenes 7100. Its deduced protein shows
      strong homology to several gamma-butyrolactone-binding proteins in Streptomyces.
      Disruption of sabR retarded nikkomycin production in liquid media containing
      glucose or glycerol as carbon source. Sporulation of sabR disruption mutants was
      earlier than the parent strain on solid media with glucose or glycerol as carbon
      source. However, disruption of sabR had no effect on either nikkomycin production
      or sporulation on media containing mannitol as carbon source, suggesting that
      sabR is a pleiotropic regulatory gene that controls the onset of nikkomycin
      production and sporulation in S. ansochromogenes and is related to the
      utilization of carbon source.

PMID- 14571972
TI  - Enhanced ribosome and tRNA contents in Escherichia coli expressing a truncated
      Vitreoscilla hemoglobin mutant analyzed by flow field-flow fractionation.
AB  - The ribosome and tRNA levels of Escherichia coli cells, transformed with a native
      or mutated Vitreoscilla hemoglobin genes (vhb), were investigated using
      asymmetrical flow field-flow fractionation (AFFFF). Mutagenesis of rhb by error
      prone PCR was carried out to alter the growth behavior of microaerobically
      cultivated native VHb-expressing E. coli. A VHb mutant, pVMT1, was identified,
      which was able to reach a remarkably high final A600 of 15, the value of which
      being 160% higher than that of a VHb control carrying pVHb8 (A600 5.8). AFFFF
      revealed that cells expressing mutant vhbs showed up to a doubling in the number
      of active 70S ribosomes cell(-1), an almost 3-fold increase in the number of
      tRNAs cell(-1), and up to a 26% increase in the mass fraction of active 70S
      ribosomes.

PMID- 14571973
TI  - Renal tissue reconstitution by the implantation of renal segments on
      biodegradable polymer scaffolds.
AB  - Renal units were created in vivo by transplanting isolated renal segments on
      three-dimensional, biodegradable polymer scaffolds. Renal segments, freshly
      isolated from rat kidneys, were seeded on polymer scaffolds and subcutaneously
      implanted in athymic mice for two and four weeks. Three-dimensional renal
      reconstructs were formed with glomeruli and tubules, showing a possibility of
      reconstituting renal structures by transplanting renal segments.

PMID- 14571974
TI  - Genetic transformation of Monascus purpureus DSM1379.
AB  - Monascus purpureus was transformed into hygromycin B resistance with hygromycin B
      phosphotransferase (hph) fused to Aspergillus nidulans trpC or a putative
      Monascus purpureus gpd1 promoter by electroporation. Among five strains, only M.
      purpureus DSM1397 was a competent recipient. Normal growth and sporulation on
      media containing up to 500 mg hygromycin B l(-1) occurred up to five generations.
      Upon transformation of the strain with the green fluorescent protein gene (sgfp)
      as a model gene and hph as a selection marker, characteristic green fluorescence
      was observed under fluoromicroscopy indicating successful transformation.

PMID- 14571975
TI  - Exopolysaccharide and extracellular metabolite production by Lactobacillus
      delbrueckii subsp. bulgaricus, grown on lactose in continuous culture.
AB  - Lactobacillus delbrueckii subsp. bulgaricus NCFB 2483, when grown on lactose in
      continuous culture, showed increasing specific yields and volumetric
      productivities of exopolysaccharide (EPS) with increasing dilution rate. Specific
      and volumetric productivities of lactate and galactose, as extracellular
      metabolites, increased in response to the incremental changes in the dilution
      rate up to 0.4 h(-1). Elevated Y(p/s) values determined for EPS (0.025 g EPS x g
      lactose(-1)) at the dilution rates of 0.3 h(-1)-0.4 h(-1), relative to those
      determined at lower dilution rates, suggest a diversion of carbon flux towards
      EPS being associated with the higher rates of growth.

PMID- 14571976
TI  - Polymerization of cardanol using soybean peroxidase and its potential application
      as anti-biofilm coating material.
AB  - Soybean peroxidase (20 mg) catalyzed the oxidative polymerization of cardanol in
      2-propanol/phospate buffer solution (25 ml, 1:1 v/v) and yielded 62% polycardanol
      over 6 h. Cobalt naphthenate (0.5% w/w) catalyzed the crosslinking of
      polycardanol and the final hardness of crosslinked polycardanol film exceeded 9 H
      scale as pencil scratch hardness, which shows a high potential as a commercial
      coating material. In addition, it showed an excellent anti-biofouling activity to
      Pseudomonas fluorescens compared to other polymeric materials such as
      polypropylene.

PMID- 14571977
TI  - A cDNA encoding vacuolar type beta-D-fructofuranosidase (Os beta fruct3) of rice
      and its expression in Pichia pastoris.
AB  - A vacuolar type beta-D-fructofuranosidase (Os beta fruct3) was cloned from
      etiolated rice seedlings cDNA library. It encodes an open reading frame of 688
      residues. The deduced amino acid sequence had 58% identity to the vacuolar type
      beta-D-fructofuranosidase of maize (Ivr1). Os beta fruct3 exists as a single copy
      per genome. Northern analyses showed that Os beta fruct3 undergoes organ-specific
      expression and is involved in the adjustment of plant responses to environmental
      signals and metabolizable sugars. Os beta fruct3 was also heterologously
      expressed in Pichia pastoris. The recombinant proteins were confirmed to be a
      vacuolar type beta-D-fructofuranosidase.

PMID- 14571978
TI  - A microbial fuel cell capable of converting glucose to electricity at high rate
      and efficiency.
AB  - A microbial fuel cell containing a mixed bacterial culture utilizing glucose as
      carbon source was enriched to investigate power output in relation to glucose
      dosage. Electron recovery in terms of electricity up to 89% occurred for glucose
      feeding rates in the range 0.5-3 g l(-1) d(-1), at powers up to 3.6 W m(-2) of
      electrode surface, a five fold higher power output than reported thus far. This
      research indicates that microbial electricity generation offers perspectives for
      optimization.

PMID- 14571979
TI  - Integrated immobilized cell reactor-adsorption system for beta-cyclodextrin
      production: a model study using PVA-cryogel entrapped Bacillus agaradhaerens
      cells.
AB  - Production of cyclodextrins (CDs) by immobilized cells of the alkaliphilic
      Bacillus agaradhaerens LS-3C with integrated product recovery was studied. The
      microorganism was entrapped in polyvinyl alcohol-cryogel beads and used as a
      convenient source of immobilized cyclodextrin glycosyltransferase (CGTase). On
      activation by incubation in the cultivation medium containing 1% (w/v) starch,
      the entrapped cells multiplied and secreted CGTase with an activity of 2-3 mg
      beta-cyclodextrin h(-1) g(-1) beads. The immobilized biocatalyst exhibited
      maximum activity at pH 9 and 50 degrees C, and formed cyclodextrins comprising 92
      94% beta-CD and remaining alpha-CD. The cyclodextrin product from the immobilized
      cell bioreactor was continuously recovered by adsorption to Amberlite XAD-4 in a
      recycle batch mode. The product adsorption was facilitated at low temperature
      while hot water was used for elution.

PMID- 14571982
TI  - Sequence analysis of cyclodextrin glycosyltransferase from the alkaliphilic
      Bacillus agaradhaerens.
AB  - The gene encoding an alkaline active cyclodextrin glycosyltransferase (CGTase)
      from the alkaliphilic B. agaradhaerens LS-3C was cloned and sequenced. It encodes
      a mature polypeptide of 679 amino acids with a molecular mass of 76,488 Da. The
      deduced amino acid sequence of the mature CGTase revealed 99 and 95% identity to
      the CGTase sequences from the other B. agaradhaerens strains, DSM 8721T and 9948,
      respectively. The next closest identity was of 59% with B. clarkii enzyme.
      CGTases from B. agaradhaerens, B. clarkii, and B. firmus/lentus formed a
      phylogenetically separated cluster from the other CGTases of Bacillus spp.
      origin. A number of usually conserved residues in the CGTases were found to be
      replaced in the sequence of B. agaradhaerens enzyme. The sequence analysis
      indicated the enzyme to be close to the so-called 'intermediary enzymes' in the
      alpha-amylase family.

PMID- 14571981
TI  - An oligosaccharide fraction from Korean mugwort herb suppresses death of the
      mouse thymocytes in culture by down-regulating the Fas death receptor gene.
AB  - Korean mugwort herb is a preparation of dried leaves from Artemisia species and
      has been used as a traditional medicine in Asia. An oligosaccharide fraction,
      AVF3, purified from the preparation promoted survival of the mouse thymocytes in
      culture. A mouse gene array study suggests that the AVF3 may modulate Fas/FasL
      dependent apoptotic cell death and thus has influence on the survival of the
      thymocytes in culture. RT-PCR analysis confirmed the down-regulation of the Fas
      gene by the AVF3 treatment, supporting that the AVF3 modulated thymocyte death by
      suppressing the Fas gene expression.

PMID- 14571980
TI  - Monoclonal antibody purification by affinity chromatography with ligands derived
      from the screening of peptide combinatory libraries.
AB  - The peptide, Ala-Pro-Ala-Arg (APAR), was selected from the screening of a
      tetrapeptide combinatorial synthetic library as the ligand for affinity
      purification of an anti-Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF)
      monoclonal antibody (Mab) developed in mouse ascitis. The affinity
      chromatographic matrix obtained by attachment of APAR to agarose, having a
      peptide density of 0.5 micromol ml(-1), showed a maximum capacity of 9.1 mg Mab
      ml(-1) and a dynamic capacity of 3.9 mg Mab ml(-1). A 95% yield of
      electrophoretically pure anti-GM-CSF was obtained in a single step.

PMID- 14571983
TI  - Molecular detection and direct enumeration of methanogenic Archaea and
      methanotrophic Bacteria in domestic solid waste landfill soils.
AB  - Methane oxidizing and producing activities of cover soil (10, 30 cm depth) and
      burial waste (1, 3 m depth) were evaluated: top cover soil (10 cm) had the
      highest methane oxidizing activity, while 1 m depth buried waste showed the
      highest methane producing potential. All the sequences of the 1 m sample were
      found to be closely related to 16S rDNAs of mainly hydrogenotrophic methanogens
      known, such as genera Methanosarcina, Methanoculleus, and Methanobacterium. We
      developed a modified fluorescence in situ hybridization (FISH) direct counting
      method for landfill samples, resulting in the detection of approx. 1% of total
      cells as archaeal cells (presumably methanogens). However, probe-positive cells
      could not be found with probes for methanotrophs by the methods.

PMID- 14571984
TI  - Production and secretion of biologically active human granulocyte-macrophage
      colony stimulating factor in transgenic tomato suspension cultures.
AB  - A complementary DNA encoding human granulocyte-macrophage colony stimulating
      factor (hGM-CSF) was cloned and introduced into tomato (Lycopersicon esculentum
      cv. Seokwang) using Agrobacterium-mediated transformation. Genomic PCR and
      Northern blot analysis demonstrated the integration of the construction into the
      plant nuclear genome and expression of the hGM-CSF in transgenic tomato. The cell
      suspension culture was established from leaf-derived calli of the transgenic
      tomato plants transformed with the hGM-CSF gene. Recombinant hGM-CSF was
      synthesized by the transgenic cell culture and secreted into the growth medium at
      45 microg l(-1) after 10 d' cultivation.

PMID- 14571985
TI  - Supercritical CO2 as a reaction medium for synthesis of capsaicin analogues by
      lipase-catalyzed transacylation of capsaicin.
AB  - Capsaicin analogues having different acyl moiety were synthesized by lipase
      catalyzed transacylation of capsaicin with a corresponding acyl donor in
      supercritical CO2 as a reaction medium. Transacylation with methyl tetradecanoate
      using Novozym 435 as a catalyst gave vanillyl tetradecanamide in a 54% yield at
      80 degrees C and 19 MPa over 72 h. Vanillyl (Z)-9-octadecenamide, olvanil, was
      synthesized from triolein in a 21% yield over 7 d.

PMID- 14571986
TI  - A biochemical-based model for the dosimetry of dietary organically bound tritium-
      Part 1: Physiological criteria.
AB  - In this paper the physiological criteria for a novel form of model are described
      whose biokinetics are governed by the overall metabolic reactions of the
      principal nutrients: carbohydrates, fats, and proteins. The biokinetics of a
      particular element are based primarily on the oxidation of glucose, fatty acids,
      and amino acids and the formation of water, carbon dioxide, and urea. The
      compartmental models proposed follow the pathways of the major elements including
      hydrogen and, hence, tritium. The parameters for two models of differing
      complexity--called the HCNO-S and HCNO-C models--were evaluated here on the basis
      of biochemical reactions; the results of compartmental analysis are reported in
      an accompanying paper. The simpler form of the HCNO model has single compartments
      representing the principal nutrients. The more complex model includes
      compartments representing the longer-term retention of carbohydrates as glycogen,
      fats as adipose tissue, and proteins in bone and soft tissues. The pool sizes and
      hydrogen transfer rates are estimated. The incorporation of biochemical reactions
      and important metabolic parameters serve to give the models a greater semblance
      of physiological merit than those currently available. For example, ingestion of
      carbohydrates results in a respiratory quotient of 1.0 and 100% of the hydrogen
      content oxidized to water, which are the same as values published in the
      literature. This form of metabolic model enables development of models for other
      isotopes, besides 3H, of the major elements of the body, e.g., 14C, 15N, 18O.

PMID- 14571987
TI  - A biochemical-based model for the dosimetry of dietary organically bound tritium-
      Part 2: Dosimetric evaluation.
AB  - In this paper the dosimetry for a novel form of physiological model, whose
      biokinetics are governed by the overall metabolic reactions of the principal
      nutrients carbohydrates, fats and proteins, is evaluated by compartmental
      analysis. Two models of differing complexity, called the HCNO-S and HCNO-C
      models, were developed from parameters evaluated in an accompanying paper. The
      simpler form has single compartments representing the principal nutrients. The
      more complex model includes compartments representing the longer-term retention
      of carbohydrates as glycogen, fats as adipose tissue, and proteins in bone and
      soft tissues. The effective doses for various tritiated intakes are the same, or
      similar, as calculated by the two HCNO models, except for tritiated protein. The
      dose coefficient for an intake of tritiated water is approximately 8% greater
      than that recommended by the ICRP when the tritium body burden is considered as a
      homogenous pool. However, when the composition of individual organs is taken into
      account, the dose coefficient for an HTO intake is approximately 22% greater than
      the ICRP value. The HCNO-C dose coefficient for OBT in a normal diet is 5.0 x 10(
      11) Sv Bq(-1), which is 1.2-fold greater than the ICRP dose coefficient for an
      OBT intake. The HCNO-C composition model gave organ and tissue doses with the
      largest range for a tritiated Reference Man dietary intake, the highest dose (red
      marrow, then breast) being around three-fold the lowest. A property of the HCNO
      models, important for bioassay analyses, is that a major part (> 90%) of an OBT
      intake is oxidized and excreted as HTO, which is physiologically more accurate
      than the current ICRP OBT model. The effective dose of specific tritiated foods,
      e.g., rice and wheat, was evaluated on the basis of their constituents.

PMID- 14571989
TI  - Effect of source intensity on ability to fixate: implications for laser safety.
AB  - During long-term viewing of a continuous light source, head and eye movements
      affect the distribution of energy deposited in the retina. Previous studies of
      eye movements during a fixation task provided data used for revising the safety
      limits for long-term viewing of such sources. These studies have been continued
      to determine the effect of source brightness on the nature of fixational eye
      movements. Volunteers fixated for 50 s on a HeNe laser (lambda = 632.8 nm) masked
      by a small aperture to produce a target subtending approximately 0.03 mrad in the
      visual field. The source was attenuated to yield corneal irradiance values in the
      range 0.6 pW cm(-2) to 6 microW cm(-2). Eye movements were recorded using a Dual
      Purkinje Image Eyetracker. The data were characterized by fixation ellipses that
      represent areas of the retina in which the image of the spot was located 68% of
      the time of each trial. Significant variation across subjects in the tightness of
      fixation was observed. Over the eight orders of magnitude of source brightness
      used in this experiment (10(-13) to 10(-6) W cm(-2)), no subject showed more than
      roughly a factor of two variation in the area of the fixation ellipse. No
      statistically significant trend in tightness of fixation as a function of source
      brightness was observed. There was no loss of ability to fixate, nor any drive to
      aversion, at the higher source intensities.

PMID- 14571988
TI  - Influences of parameter uncertainties within the ICRP-66 respiratory tract model:
      a parameter sensitivity analysis.
AB  - An important aspect in model uncertainty analysis is the evaluation of input
      parameter sensitivities with respect to model outcomes. In previous publications,
      parameter uncertainties were examined for the ICRP-66 respiratory tract model.
      The studies were aided by the development and use of a computer code LUDUC (Lung
      Dose Uncertainty Code) which allows probabilities density functions to be
      specified for all ICRP-66 model input parameters. These density functions are
      sampled using Latin hypercube techniques with values subsequently propagated
      through the ICRP-66 model. In the present study, LUDUC has been used to perform a
      detailed parameter sensitivity analysis of the ICRP-66 model using input
      parameter density functions specified in previously published articles. The
      results suggest that most of the variability in the dose to a given target region
      is explained by only a few input parameters. For example, for particle diameters
      between 0.1 and 50 microm, about 50% of the variability in the total lung dose
      (weighted sum of target tissue doses) for 239PuO2 is due to variability in the
      dose to the alveolar-interstitial (AI) region. In turn, almost 90% of the
      variability in the dose to the AI region is attributable to uncertainties in only
      four parameters in the model: the ventilation rate, the AI deposition fraction,
      the clearance rate constant for slow-phase absorption of deposited material to
      the blood, and the clearance rate constant for particle transport from the AI2 to
      bb1 compartment. A general conclusion is that many input parameters do not
      significantly influence variability in final doses. As a result, future research
      can focus on improving density functions for those input variables that
      contribute the most to variability in final dose values.

PMID- 14571990
TI  - Long-term stewardship of the environmental legacy at restored sites within the
      Department of Energy nuclear weapons complex.
AB  - It is readily apparent, as the Department of Energy Office of Environmental
      Management proceeds in remediating its vast network of contaminated nuclear
      weapons facilities, that final cleanup at many facilities will not be performed
      to a level allowing unrestricted use of the facility. Instead, these facilities
      must rely on engineering, administrative, and institutional controls to ensure
      the level of cleanup performed at the site remains adequately protective of
      public health and the environment. In order for these controls to remain
      effective, however, a plan for long-term stewardship of these sites must be
      developed that is approved by the U.S. Congress. Although this sounds simple
      enough for the present, serious questions remain regarding how best to implement
      a program of stewardship to ensure its effectiveness over time, particularly for
      sites with residual contamination of radionuclides with half-lives on the order
      of thousands of years. Individual facilities have attempted to answer these
      questions at the site-specific level. However, the complexities of the issues
      require federal support and oversight to ensure the programs implemented at each
      of the facilities are consistent and effective. The Department of Energy recently
      submitted a report to Congress outlining the extent of long-term stewardship
      needs at each of its facilities. As a result, the time is ripe for forward
      thinking Congressional action to address the relevant issues and ensure the
      remedy of long-term stewardship successfully carries out its intended purpose and
      remains protective of public health and the environment. The regulatory elements
      necessary for the stewardship program to succeed can only be implemented through
      the plenary powers of the U.S. Congress.

PMID- 14571991
TI  - Comparative bias associated with various estimates of dose to maximally exposed
      individuals.
AB  - Protection of the environment from anthropogenic radiation is a resurging
      international interest. The paradigm currently in use argues that the population
      is adequately protected if dose rates to the maximally exposed individuals are
      below a certain limit. Based on data sampled from natural populations, resource
      managers need to be able to test the hypothesis that dose rates to the maximally
      exposed individuals are acceptable. Recognizing the difficulty of sampling the
      maximally exposed individual within a contaminated environment, risk assessors
      have used various alternative approaches that vary from changing the paradigm and
      applying recommended dose rate limits to representatively, rather than maximally,
      exposed individuals, to using the 95th percentile of the sample mean as an
      estimator of the population maximum. To determine the effectiveness of numerous
      proposed alternatives, we used computer simulation techniques to generate a
      "population" of doses with known distributional qualities and then mathematically
      "sampled" the population to compare the ability of the various statistics at
      estimating the known population maximum. The simulation procedure was repeated
      1000 times using Monte Carlo techniques, each time producing a measure of the
      distance between the estimate and the true value. We were thus able to quantify
      the bias associated with several approaches used to determine compliance with
      dose rate criteria established by the Department of Energy for protecting biota.
      The 95th quantile of the sample mean, and the sample maximum underestimated the
      population maximum by as much as 72 and 44%, respectively. The maximum likelihood
      estimate (MLE) of the 99.99th percentile was found to be the best predictor of
      the population maximum, even for small sample sizes of 20 and for both normally
      and lognormally distributed populations. However, bias associated with the MLE
      increased significantly if the population's distribution was incorrectly
      identified. We suggest shifting the regulatory criterion appropriately to argue
      that if the top 1% (as opposed to the maximum) of the population has a dose rate
      less than or equal to the regulatory limit then the population is adequately
      protected, and then using the MLE of the 99th percentile as the least biased
      sample statistic. Results of this study are also relevant when estimating dose to
      critical sub-groups of humans whose lifestyles are such that their doses are
      among the maximum for the population.

PMID- 14571992
TI  - Natural radiation exposure in the vicinity of Spanish nuclear power stations.
AB  - Nationwide and regional surveys have been conducted to evaluate natural radiation
      exposure of people in the vicinity of the Spanish nuclear power stations. In
      these surveys, indoor radon, external gamma dose rates outdoors and indoors and
      radioactivity in soils were measured. Measurements of indoor radon concentrations
      were performed in 214 dwellings by using nuclear track-etched detectors. External
      exposure from terrestrial gamma rays outdoors and indoors were measured in a
      total of 596 points. Radioactivity in soil samples collected at 293 sampling
      sites are also reported in this paper. By taking into account all sources of
      natural radiation exposure, mean annual effective doses to the population in the
      surroundings of the six Spanish nuclear power stations have been estimated and
      compared with those coming from their normal operation.

PMID- 14571993
TI  - A quantitative method for optimized placement of continuous air monitors.
AB  - Alarming continuous air monitors (CAMs) are a critical component for worker
      protection in facilities that handle large amounts of hazardous materials. In
      nuclear facilities, continuous air monitors alarm when levels of airborne
      radioactive materials exceed alarm thresholds, thus prompting workers to exit the
      room to reduce inhalation exposures. To maintain a high level of worker
      protection, continuous air monitors are required to detect radioactive aerosol
      clouds quickly and with good sensitivity. This requires that there are sufficient
      numbers of continuous air monitors in a room and that they are well positioned.
      Yet there are no published methodologies to quantitatively determine the optimal
      number and placement of continuous air monitors in a room. The goal of this study
      was to develop and test an approach to quantitatively determine optimal number
      and placement of continuous air monitors in a room. The method we have developed
      uses tracer aerosol releases (to simulate accidental releases) and the
      measurement of the temporal and spatial aspects of the dispersion of the tracer
      aerosol through the room. The aerosol dispersion data is then analyzed to
      optimize continuous air monitor utilization based on simulated worker exposure.
      This method was tested in a room within a Department of Energy operated plutonium
      facility at the Savannah River Site in South Carolina, U.S. Results from this
      study show that the value of quantitative airflow and aerosol dispersion studies
      is significant and that worker protection can be significantly improved while
      balancing the costs associated with CAM programs.

PMID- 14571994
TI  - Increased radon detection sensitivity: extraction from 200 ml of water and liquid
      scintillation counting.
AB  - To increase detection sensitivity in a radon ground-water monitoring program,
      radon is extracted and transferred from 200 mL of water to a liquid scintillator
      by bubbling and circulating air through the two liquids in a closed system using
      a peristaltic pump. This results in a count rate that is 11 times higher than for
      samples prepared by the most widely used method, where 10 mL of water are added
      to 10 mL of scintillator. Preparation of counting samples is simple and takes 4
      min. Standard deviation in radon concentration is 5% and minimum detectable
      activity is 5 mBq L(-1), using a counter with a background of 3 counts per hour
      and a counting time of 3 h. This method is also suitable for the measurement of
      radium in water.

PMID- 14571995
TI  - Non-destructive determination of 224Ra, 226Ra and 228Ra concentrations in
      drinking water by gamma spectroscopy.
AB  - The U.S. Environmental Protection Agency mandates that drinking water showing
      gross alpha-activity greater than 0.19 Bq L(-1) should be analyzed for radium, a
      known human carcinogen. The recommended testing methods are intricate and
      laborious. The method reported in this paper is a direct, non-destructive gamma
      spectroscopic method for the determination of 224Ra, 226Ra, and 228Ra, the three
      radium isotopes of environmental concern in drinking water. Large-volume
      Marinelli beakers (4.1-L capacity), especially designed for measuring radioactive
      gases, in conjunction with a low-background, high-efficiency (131%) germanium
      detector were used in this work. It was first established that radon, the gaseous
      decay product of radium, and its progeny are quantitatively retained in this
      Marinelli beaker. The 224Ra, 226Ra, and 228Ra activity concentrations are
      determined from the equilibrium activities of their progeny: 212Pb, 214Pb
      (214Bi), and 228Ac; and the gamma-lines used in the analysis are 238.6, 351.9
      (and 609.2), and 911.2 keV, respectively. The 224Ra activity is determined from
      the first 1,000-min measurement performed after expulsion of radon from the
      sample. The 226Ra activity is determined from the second, 2,400-min measurement,
      made 3 to 5 d later, and the 228Ra activity is determined from either the first
      or the second measurement, depending on its concentration level. The method's
      minimum detectable activities are 0.017 Bq L(-1), 0.020 Bq L(-1), and 0.027 Bq L(
      1) for 224Ra, 226Ra, and 228Ra, respectively, when measured under radioactive
      equilibrium. These limits are well within the National Primary Drinking Water
      Regulations required limit of 0.037 Bq L(-1) for 226Ra and for 228Ra. The
      precision and accuracy of the method, evaluated using the U.S. Environmental
      Protection Agency and the Environmental Resource Associates' quality control
      samples, were found to be within acceptable limits.

PMID- 14571996
TI  - Comment on: the interference of medical radionuclides with occupational in vivo
      gamma spectroscopy.

PMID- 14571997
TI  - Comment on paper by Hayes, Haskell, and Kenner.

PMID- 14571998
TI  - Using motion analysis data for foot-floor contact detection.
AB  - A simple, fast and straightforward method was developed for automatically
      deriving foot-floor contact information from tracking motion analysis system
      markers attached to the shoes of the subjects. The method was based on an
      accurate calibration of the motion analysis system prior to the experiments and a
      trivial off-line threshold-based algorithm using dedicated foot-attached marker
      positions and velocities as inputs. The main purpose of the method was to obtain
      the results almost instantaneously. The accuracy was poorer when compared with
      the classic, man-assisted and time-consuming methods, but the average error was
      less than 0.1 s compared with the force plate or pressure insole/foot switch
      based methods. The method eliminates the need for foot switches when a motion
      analysis system is already being used. As encumbrance is reduced for the
      subjects, the method is also applicable to pathological gait patterns.

PMID- 14571999
TI  - New instrumental set for the assessment of the hand functionality.
AB  - Hand motor deficits have been widely investigated, and several devices have been
      proposed for the selective and accurate study of specific hand motor tasks. Most
      studies have focused on the four, long fingers. The thumb function, although
      extremely important for the performance of most daily activities involving the
      hand, has scarcely been documented. A set of general-purpose, instrumental
      measuring devices has been designed and constructed at the authors' laboratory to
      measure and monitor the force each finger exerts separately, under isometric
      conditions, during pressing tasks. More generally, it is meant for the functional
      evaluation of the normal hand in different postures, but it also provides
      reliable measurements of the injured or deformed hand. The instrumental set is
      suitable for both biomechanical research and clinical applications. Effectively
      integrated with a visual feedback tool, it could be exploited in delivering and
      monitoring custom-designed rehabilitation programmes. The characteristics of the
      force transducers (range 0-100 N) were: inter-axis crosstalk < 4%; non-linearity
      < +/- 0.4% f.s.; hysteresis < 0.3% f.s.; overall accuracy +/- 1% f.s. The overall
      measurement system resolution was better than 0.1 N, and the keys response to the
      mechanical shock (acquired at 10 kHz) showed a resonance frequency of about 1
      kHz. It was observed that the thumb contributed more than 30% of the overall
      pressing force.

PMID- 14572000
TI  - Some technical aspects of magnetic stimulation coil design with the ferromagnetic
      effect.
AB  - The performance of the stimulation coil in a magnetic nerve stimulator can be
      improved by attaching a ferromagnetic structure to the coil. This reduces heat
      generation at the coil and increases magnetic field strength for a given unit of
      current. Some technical aspects of the design of a stimulation coil with a
      ferromagnetic structure have been studied. Finite element method analysis results
      are presented for the effect of size, depth and magnetic saturation of the
      ferromagnetic structure on the stimulation coil performance. The experimental
      results show that the stimulation coil performance is improved by up to 40% by
      the attaching of a ferromagnetic structure on the coil.

PMID- 14572001
TI  - Improvement of patient return electrodes in electrosurgery by experimental
      investigations and numerical field calculations.
AB  - Numerical field calculations and experimental investigations were performed to
      examine the heating of the surface of human skin during the application of a new
      electrode design for the patient return electrode. The new electrode is
      characterised by an equipotential ring around the central electrode pads. A multi
      layer thigh model was used, to which the patient return electrode and the active
      electrode were connected. The simulation geometry and the dielectric tissue
      parameters were set according to the frequency of the current. The temperature
      rise at the skin surface due to the flow of current was evaluated using a two
      step numerical solving procedure. The results were compared with experimental
      thermographical measurements that yielded a mean value of maximum temperature
      increase of 3.4 degrees C and a maximum of 4.5 degrees C in one test case. The
      calculated heating patterns agreed closely with the experimental results.
      However, the calculated mean value in ten different numerical models of the
      maximum temperature increase of 12.5 K (using a thermodynamic solver) exceeded
      the experimental value owing to neglect of heat transport by blood flow and also
      because of the injection of a higher test current, as in the clinical tests. The
      implementation of a simple worst-case formula that could significantly simplify
      the numerical process led to a substantial overestimation of the mean value of
      the maximum skin temperature of 22.4 K and showed only restricted applicability.
      The application of numerical methods confirmed the experimental assertions and
      led to a general understanding of the observed heating effects and hotspots.
      Furthermore, it was possible to demonstrate the beneficial effects of the new
      electrode design with an equipotential ring. These include a balanced heating
      pattern and the absence of hotspots.

PMID- 14572002
TI  - Haemodynamic considerations in the design of a skeletal muscle ventricle.
AB  - Skeletal muscle ventricles (SMVs) configured to operate as diastolic
      counterpulsators show promise as cardiac assist devices. In four pigs, SMVs were
      connected to the aorta by a single-limbed conduit and activated during every
      third cardiac diastole. During the assisted beats, mean diastolic aortic pressure
      increased by 30.3 +/- 2.2%, peak diastolic aortic pressure increased by 38.5 +/-
      2.7%, the endocardial viability ratio increased by 42.3 +/- 3.4%, and mean left
      anterior descending coronary artery flow increased by 61.6 +/- 4.5%. Although
      there are major advantages to making the connection to the aorta by a single-limb
      conduit, the lack of separation between inlet and outlet means that such devices
      must be designed carefully to avoid thrombogenesis under chronic conditions.
      Design rules were developed for this configuration, based on earlier in vitro
      studies. They addressed the problem of stasis by promoting the development of a
      propagating vortex that travels the length of the ventricle and ensured proper
      exchange of blood with the circulation by limiting the volume of the connecting
      conduit. An SMV compatible with these rules was connected in a pig. At elective
      termination 1 week later, activation of the SMV increased peak diastolic pressure
      by 20.1% and reduced left-ventricular stroke work in the post-assisted beat by
      10.1%. The SMV was free from thrombus.

PMID- 14572003
TI  - Gender differences in stability of the instantaneous patterns of body surface
      potentials during ventricular repolarisation.
AB  - Women have a higher risk of developing torsade de pointes under OT-prolonging
      conditions. The electrophysiological differences between the sexes that could
      account for this are largely unknown. The objective of the work was to evaluate
      gender differences in repolarisation potentials using a method that is
      independent of the specific electrical properties of the thorax. 1410 normal
      recordings from the Glasgow 12-lead ECG database and 52 normal ECG maps obtained
      separately in Milan were analysed. The average difference between 1 and the
      correlation coefficient of the instantaneous pattern at the peak of T with that
      at every other instant is called the early repolarisation deviation index (ERDI)
      for J-T peak and the late repolarisation deviation index (LRDI) for T peak-T end.
      In standard ECG recordings, the ERDI was 0.42 +/- 0.22 in females compared with
      0.19 +/- 0.16 in males (p < 10(-6)). The LRDI was higher in males under the age
      of 50. In body surface maps, the ERDI was 0.32 +/- 0.21 in females against 0.16
      +/- 0.17 in males (p < 0.01), and the LRDI was non-significantly higher in males.
      The pattern of instantaneous body surface potentials showed gender differences
      during repolarisation with a method that is independent of the electrical
      properties of the thorax.

PMID- 14572004
TI  - Multi- and monofractal indices of short-term heart rate variability.
AB  - Indices of heart rate variability (HRV) based on fractal signal models have
      recently been shown to possess value as predictors of mortality in specific
      patient populations. To develop more powerful clinical indices of HRV based on a
      fractal signal model, the study investigated two HRV indices based on a
      monofractal signal model called fractional Brownian motion and an index based on
      a multifractal signal model called multifractional Brownian motion. The
      performance of the indices was compared with an HRV index in common clinical use.
      To compare the indices, 18 normal subjects were subjected to postural changes,
      and the indices were compared on their ability to respond to the resulting
      autonomic events in HRV recordings. The magnitude of the response to postural
      change (normalised by the measurement variability) was assessed by analysis of
      variance and multiple comparison testing. Four HRV indices were investigated for
      this study: the standard deviation of all normal R-R intervals; an HRV index
      commonly used in the clinic; detrended fluctuation analysis, an HRV index found
      to be the most powerful predictor of mortality in a study of patients with
      depressed left ventricular function; an HRV index developed using the maximum
      likelihood estimation (MLE) technique for a monofractal signal model; and an HRV
      index developed for the analysis of multifractional Brownian motion signals. The
      HRV index based on the MLE technique was found to respond most strongly to the
      induced postural changes (95% CI). The magnitude of its response (normalised by
      the measurement variability) was at least 25% greater than any of the other
      indices tested.

PMID- 14572005
TI  - A novel heart/trunk simulator for the study of electromagnetic interference with
      active implantable devices.
AB  - This paper describes a portable heart simulator for the study of electromagnetic
      interference with active implantable devices. The simulator consists of plexiglas
      box divided into three chambers simulating the left atrium and the ventricles,
      plus a lateral compartment for the implantable device. The box is linked to a
      laptop computer by an analogue-to-digital convertor board, and the three chambers
      are monitored and driven by dedicated hardware and software interfaces. Synthetic
      endocardial atrial and ventricle signals for 13 cardiac rhythms are stored in the
      computer. They are applied to the cardiac chambers by AgCl plates. Sensing
      electrodes are in the form of AgCl needles inserted in saline. The simulator was
      able to demonstrate the behaviour of three pacemakers tested in the absence and
      presence of electromagnetic interference, generated by mobile phones (European
      GSM 900 and 1800 MHz) that emitted up to 2W (1 W at 1800 MHz). Pacemakers can be
      programmed with sensitivity from 0.1 mV to 5 mV, pulse width from 0.1 ms to 1.5
      ms and pulse amplitude from 0.5 V to 5 V. The structural separation in three
      cardiac chambers (plus the one for the device) allowed a fast analysis procedure
      for dual- and tri-chamber implantable devices.

PMID- 14572006
TI  - Beat-to-beat repolarisation variability in body surface electrocardiograms.
AB  - The repolarisation variability in body surface electrocardiograms has been
      evaluated by beat-to-beat QT interval variability. Interpolated R-peak time and
      template T-wave matching algorithms were used to determine the characteristic
      time points of the R-wave and T-wave, respectively. The T-wave time can be
      determined accurately and robustly by searching for the best match between a
      template T-wave and measured T-waves. The authors studied 5 min multichannel ECG
      recordings (35 channels) measured in 20 healthy subjects. A QT variability of
      2.24 +/- 0.79 ms was obtained (1.15 +/- 0.30 ms, if linear detrend was used),
      which is significantly lower than that reported in several other studies. To
      explore this discrepancy, the sensitivity of the template matching algorithm to
      periodic and random noise on the ECG was estimated by a simulation study. The
      results showed that the repolarisation variability depended on selection of the
      appropriate lead, the signal-to-noise ratio and the effectiveness of baseline
      correction. Lead II of a standard 12-lead ECG is a reasonable choice for QT
      variability analysis; however, precordial leads V3-V6 could be better with regard
      to the amplitude of the T-wave. Poor signal-to-noise ratios can lead to
      unrealistic values for repolarisation variability.

PMID- 14572008
TI  - Chamber for indirect calorimetry with accurate measurement and time
      discrimination of metabolic plateaus of over 20 min.
AB  - A robust algorithm for pull-calorimeters that provides a rapid response to
      changes in respiratory gas exchange has been implemented. Metabolic plateaus
      (over 20 min), such as that generated by steady treadmill exercise, can be
      measured accurately (< 2.0% error for an energy expenditure level of 16.7 kJ min(
      1)). The time resolution for changes between plateaus can be accurately found
      with 1 min discrimination. Implementation required only software changes but no
      structural or instrumentation changes to the chamber. The algorithm was based on
      the one developed for the push-calorimeter at the Sahlgrenska Hospital in Sweden.
      The method utilises published equations for the rate of O2 consumption and CO2
      production in the chamber, along with techniques for suppressing noise and
      identifying trends. Using the exact solution of the equations for steady state,
      the O2 concentrations from the preceding 30 min period are fitted to two
      connected exponential segments, of variable length, using the least-squares
      method. The smoothed O2 concentration and associated time derivative are then
      determined for the time point 15 min earlier and substituted into the respiration
      equations. The CO2 concentrations are subjected to the same analysis. The process
      is repeated every minute, and the newly computed rates of O2 consumption and CO2
      production, as well as metabolic rate, are then presented. Gas injection tests
      proved that the chamber can respond instantaneously to a change from one steady
      state of respiration to another and correctly averages repeated changes in
      respiration with periods less than 15min (< 1.4% error for simulated, alternating
      O2 consumption levels of 0.81 min (-1) and 0.01 min). The successful integration
      of the algorithm into the Pennington chambers allows for traditional 24 h energy
      expenditure measurements and various metabolic experiments requiring rapid
      responses.

PMID- 14572007
TI  - Coronary artery disease diagnosis based on exercise electrocardiogram indexes
      from repolarisation, depolarisation and heart rate variability.
AB  - Several indexes have been reported to improve the accuracy of exercise test
      electrocardiogram (ECG) analysis in the diagnosis of coronary artery disease
      (CAD), compared with the classical ST depression criterion. Some of them combine
      repolarisation measurements with heart rate (HR) information (such as the so
      called ST/HR hysteresis); others are obtained from the depolarisation period
      (such as the Athens QRS score); finally, there are heart rate variability (HRV)
      indexes that account for the nervous system activity. The aim of this study was
      to identify the best exercise ECG indexes for CAD diagnosis. First, a method to
      automatically estimate repolarisation and depolarisation indexes in the presence
      of noise during a stress test was developed. The method is divided into three
      stages: first, a preprocessing step, where QRS detection, filtering and baseline
      beat rejection are applied to the raw ECG, prior to a weighted averaging;
      secondly, a post-processing step in which potentially noisy averaged beats are
      identified and discarded based on their noise variance; finally, the measurement
      step, in which ECG indexes are computed from the averaged beats. Then, a
      multivariate discriminant analysis was applied to classify patients referred for
      the exercise test into two groups: ischaemic (positive coronary angiography) and
      low-risk (Framingham risk index < 5%). HR-corrected repolarisation indexes
      improved the sensitivity (SE) and specificity (SP) of the classical exercise test
      (SE = 90%, SP = 79% against SE = 65%, SP = 66%). Depolarisation indexes also
      achieved an improvement over ST depression measurements (SE = 78%, SP = 81%). HRV
      indexes obtained the best classification results in our study population (SE =
      94%, SP = 92%) by means of the very high-frequency power (VHF) (0.4-1 Hz) at
      stress peak.

PMID- 14572009
TI  - Mathematical study of the role of non-linear venous compliance in the cranial
      volume-pressure test.
AB  - The role of the cerebral venous bed in the cranial volume-pressure test was
      examined by means of a mathematical model. The cerebral vascular bed was
      represented by a single arterial compartment and two venous compartments in
      series. The lumped-parameter formulation for the vascular compartments was
      derived from a one-dimensional theory of flow in collapsible tubes. It was
      assumed in the model that the cranial volume is constant. The results show that
      most of the additional volume of cerebrospinal fluid (deltaV(CSF)) was
      accommodated by collapse of the cerebral venous bed. This profoundly altered the
      venous haemodynamics and was reflected in the cranial pressure P(CSF). The
      cranial volume-pressure curve obtained from the model was consistent with
      experimental data; the curve was flat for 0 < or = deltaV(CSF) < or = 20 ml and
      35 < or = deltaV(CSF) < or = 40 ml, and steep for 20 < or = deltaV(CSF) < or = 35
      ml and deltaV(CSF) > or = 40 ml. For deltaV(CSF) > 25 ml and P(CSF) > 5.3 kPa (40
      mmHg), cerebral blood flow dropped. When P(CSF) was greater than the mean
      arterial pressure, all the veins collapsed. The conclusion of the study was that
      the shape of the cranial volume-pressure curve can be explained by changes in the
      venous bed caused by various degrees of collapse and/or distension.

PMID- 14572010
TI  - Simulation framework for electrophysiological networks: effect of syncytial
      properties on smooth-muscle synaptic potentials.
AB  - A building block-based software framework was developed to simulate
      electrophysiological networks. The synaptic potentials generated during
      neurotransmission were simulated in an existing discrete bidomain model of smooth
      muscle, using cubic, three-dimensional grids of varying sizes. The model is
      automatically derived and numerically solved, and the results of the simulation
      agree with previous results obtained analytically. An enhanced model was also
      proposed, incorporating an additional (junctional) capacitance in the network.
      The correctness of the model was verified, and the effect of the extra
      capacitance on the synaptic potentials was explored. It was found that, with a
      junctional capacitance C(i) of 1.4 x 10(-10) F incorporated, the peak amplitude
      of the spontaneous excitatory junction potential V(peak) declined by
      approximately 13% at node 0 and by approximately 37% at node 3x for a system size
      of 9(3). Similar results were obtained for different system sizes. V(peak) also
      declined as the junctional capacitance Ci was increased. In a system of size
      11(30, a 200-fold increase in C(i) induced a 55% reduction at node 0. It is
      suggested that the type of modular simulation framework developed here may find
      general applicability for simulations of other physiological systems.

PMID- 14572011
TI  - Artificial neural network detects changes in electro-encephalogram power spectrum
      of different sleep-wake states in an animal model of heat stress.
AB  - An effective application is presented of a back-propagation artificial neural
      network (ANN) in differentiating electro-encephalogram (EEG) power spectra of
      stressed and normal rats in three sleep-wakefulness stages. The rats were divided
      into three groups, one subjected to acute heat stress, one subjected to chronic
      heat stress and one a handling control group. The polygraphic sleep recordings
      were performed by simultaneous recording of cortical EEG, electro-oculogram (EOG)
      and electromyogram (EMG) on paper and in digital form on a computer hard disk.
      The preprocessed EEG signals (after removal of DC components and reduction of
      baseline movement) were fragmented into 2 s artifact-free epochs for the
      calculation of power spectra. The slow-wave sleep (SWS), rapid eye movement (REM)
      sleep and awake (AWA) states were analysed separately. The power spectrum data
      for all three sleep-wake states in the three groups of rats were tested by a back
      propagation ANN. The network contained 60 nodes in the input layer, weighted from
      power spectrum data from 0 to 30 Hz, 18 nodes in the hidden layer and an output
      node. The ANN was found effective in differentiating the EEG power spectra from
      stressed to normal spectral patterns following acute (92% in SWS, 85.5% in REM
      sleep, 91% in AWA state) as well as chronic heat exposure (95.5% in SWS, 93.8% in
      REM sleep, 98.5% in AWA state).

PMID- 14572012
TI  - Adaptive approximation of the boundary surface of a neuron in confocal microscopy
      volumetric images.
AB  - In biomedical visualisation, the isosurface is usually used to represent
      (approximate) the boundary surface of the structure within biomedical volumetric
      images. However, in many confocal microscopy volumetric images of neurons, the
      grey values of the object and/or background are usually uneven. Therefore a fixed
      isosurface is not suitable for use in approximating the boundary surface of the
      neuron. A method is proposed to construct the adaptively approximating surface of
      the boundary surface of the neuron. In this method, the boundary surface of the
      neuron could be locally and adaptively approximated with different surface
      patches in different local regions. Consequently, the approximation accuracy has
      been considerably improved.

PMID- 14572013
TI  - Predictors of long-term adherence to pelvic floor muscle exercise therapy among
      women with urinary incontinence.
AB  - This study assessed predictors of long-term adherence to pelvic floor muscle
      exercise (PFME) therapy including a health education programme among women with
      urinary incontinence. Sequential multiple regression analyses revealed several
      significant predictors that predicted 50% of variance in long-term adherence
      behavior. Short-term adherence significantly predicted long-term adherence.
      Further, women with frequent weekly wet episodes before and 1 year after therapy
      were more likely to have high adherence levels 1 year after therapy than women
      with fewer weekly losses. Thus, women seemed to adapt long-term adherence
      behavior to their symptoms. Adherence to PFME therapy was very high. The protocol
      checklist for the PFME therapy developed to standardize treatment among
      physiotherapists had structured therapy content, which may have optimized
      adherence behavior in this study. Implementation of this protocol checklist in
      clinical guidelines is suggested.

PMID- 14572014
TI  - When more is better: number of motives and reasons for quitting as correlates of
      physical activity in women.
AB  - Understanding the mechanisms by which physical activity is influenced is
      particularly relevant for health promotion efforts aimed at women, who display
      lower levels of physical activity and may experience more barriers to exercise
      than men. This study examined the number of motives for exercise and the number
      of reasons for previous quitting as predictors of exercise behavior.
      Specifically, the cognitive complexity of motives for exercise and reasons for
      quitting, as indicators of exercise-related memory associations that reflect
      cognitive structure, were evaluated. In a sample of 394 women aged 17-54, number
      of reasons for quitting did not predict current exercise level. However, more
      elaborated memory networks for motives were highly related to current exercise
      behavior, except among women with high Center for Epidemiologic Studies
      Depression Scale scores. These results support the predictive superiority of
      positive over negative memory associations found in studies on attitude
      accessibility in other behaviors, such as substance use, among women of normal
      mood and suggest a moderating effect of depression.

PMID- 14572015
TI  - Health care practitioners' motivation for tobacco-dependence counseling.
AB  - Smoking cessation counseling by practitioners occurs at low rates in spite of
      strong evidence that counseling increases quit rates and reduces patient
      mortality. In a preliminary study, 1060 New York State physicians completed a
      survey concerning use of the Agency for Health Care Policy and Research (AHCPR)
      Guidelines, perceived autonomy and perceived competence for counseling, perceived
      autonomy support from insurers, and barriers to counseling. Considered together,
      perceived autonomy, perceived competence and perceived autonomy support predicted
      time devoted to counseling and use of the AHCPR guidelines. The primary,
      longitudinal study of 220 health care practitioners who attended a smoking
      cessation workshop predicted change in the practitioners' perceived autonomy and
      perceived competence for counseling as a function of the degree to which they
      experienced the workshop instructor as autonomy-supportive. In turn, change in
      perceived autonomy predicted change in time spent counseling and change in use of
      the AHCPR guidelines.

PMID- 14572016
TI  - Filthy or fashionable? Young people's perceptions of smoking in the media.
AB  - Research has shown that the media over-estimates smoking rates and often
      associates smoking with favorable attributes or situations. Given that the media
      plays a large role in influencing youth culture, portrayal of smoking in the
      media is of concern. In order to explore young people's perceptions of smoking
      imagery in the media, 16 focus groups were conducted with 117 school students.
      Participants were asked to rate smoking images selected from audio-visual and
      print media, and to discuss their perceptions of these images. The results showed
      that young people perceived smoking in these media selections to be normal and
      acceptable. They identified with the stress-relieving and social aspects of
      smoking, despite being well aware of the harmful health effects. Its
      acceptability as part of a 'cool' image was also noted. Positive images of
      smoking in the media have the potential to down-play the serious health
      consequences of smoking by portraying it in a way that young people interpret as
      a normal part of everyday life. They may also encourage a more neutral or
      tolerant attitude towards smoking among young people and therefore act to
      counteract other health promotion efforts to reduce teenage smoking.

PMID- 14572017
TI  - Practising what we preach? A practical approach to bringing research, policy and
      practice together in relation to children and health inequalities.
AB  - This paper explores the need for better links between research and practice in
      relation to work with children and health inequalities. Despite continuing
      discussion about the need to improve dissemination of research activity in
      general, study of this area remains largely neglected. As a result, despite the
      rhetoric, the research and practice gap continues to exist. An attempt to remedy
      this was undertaken through the support of a user fellowship as part of the UK
      Economic and Social Research Council Health Variations Programme. The paper
      describes a number of activities that were undertaken during the fellowship, and
      discusses the implications of these for improving connections and minimizing the
      research and practice 'gap'. It argues that a need exists for researchers to
      develop innovative dissemination strategies and suggests that potential exists
      for an interactive model of dissemination. Such a model implies a more active
      role for users of research in the shaping of research agendas.

PMID- 14572018
TI  - School differences in pupil smoking: a consequence of a trade-off between health
      and education agendas?
AB  - Current policy documents stress that raising standards in education and health
      are inextricably linked, with schools identified as well placed to advance both
      agendas. This paper considers these assumptions in the light of data derived from
      27 staff interviews conducted in two secondary schools. These schools served
      relatively disadvantaged communities, but differed in their pupil smoking rates
      with one school being 'high-smoking', the other 'low-smoking'. It explores
      whether this difference reflects the differential emphasis placed by each school
      on education or health. Analysis reveals that the 'low-smoking' school subscribes
      to holistic values and operates according to a child-centred bottom-up philosophy
      offering a differentiated programme of pupil support contingent on needs. In
      contrast, the 'high-smoking' school maintains a narrow focus on educational
      outcomes, and its high expectations are viewed as running counter to those held
      by pupils and parents. The contrasting school philosophies bring different
      unintended consequences. The holistic focus of the low-smoking school is
      associated with tempered educational expectations, thus conflicting with
      recommendations in education policies. The singular education focus of the high
      smoking school leaves little room for a health agenda, and can overlook and
      disenfranchise the educationally disinclined. The school systems' impact on pupil
      engagement may explain their different smoking rates.

PMID- 14572019
TI  - The effects of clean indoor air laws: what do we know and what do we need to
      know?
AB  - Our objective was to review the research on the effects of public clean air laws
      on smoking rates, compare these effects to those found in studies on the impact
      of private worksite restrictions and derive estimates of the potential reductions
      in smoking rates that might be expected from the implementation of the two types
      of policies. Data sources were computerized databases, references identified from
      pertinent peer-reviewed journal articles and books, and suggestions by experts on
      tobacco control policy. Comprehensive public clean air laws have the potential to
      reduce prevalence and consumption rates of the entire population (including non
      working and non-indoor working smokers) by about 10%. Studies on private worksite
      regulations also suggest that strong worksite restrictions have the potential to
      reduce the prevalence rate of the entire population by about 6% over the long
      term and the quantity smoked by continuing smokers by 28%, depending on the
      length of time after the ban. Further research is needed on the effects of the
      different types of public clean air policies on the entire smoking population and
      on different sociodemographic groups, how the effects of public clean indoor air
      laws depend on private restrictions already in place, and how the effect of
      private restrictions depend on whether or not they are supported by public clean
      air laws.

PMID- 14572020
TI  - The European Smoking Prevention Framework Approach (EFSA): an example of integral
      prevention.
AB  - A smoking prevention project in six European countries (European Smoking
      prevention Framework Approach) was developed, featuring activities for
      adolescents, schools and parents, including out-of-school activities. Consensus
      meetings resulted in agreement between the countries on goals, objectives and
      theoretical methods. Countries' specific objectives were also included. National
      diversities required country-specific methods to realize the goals and
      objectives. The community intervention trial was used as the research design.
      Since interventions took place at the community level, communities or regions
      were allocated at random to the experimental or control conditions. Complete
      randomization was achieved in four countries. At baseline, smoking prevalence
      among 23 125 adolescents at the start of the project was 5.6% for regular smoking
      and 4.0% for daily smoking. Smoking prevalence rates were higher among girls than
      boys in all countries as far as weekly smoking was concerned. Process evaluations
      revealed that the project's ambitions were high, but were limited by various
      constraints including time and delays in receiving funds. Future smoking
      prevention projects should aim to identify the effective components within the
      social influence approach as well as within broader approaches and on reaching
      sustained effects.

PMID- 14572022
TI  - From global effectiveness to joint strategy development in England.

PMID- 14572021
TI  - Parents' and friends' smoking status as predictors of smoking onset: findings
      from six European countries.
AB  - This study assessed the relationship between the smoking behavior of adolescents
      and the smoking status of their parents and friends among adolescents from six
      European countries. A longitudinal study collected data from 15 705 adolescents
      on their own smoking status, and that of their parents, best friend and friends
      in general. Cross-sectional regression analysis showed that adolescent smoking
      was most strongly associated with friends' smoking and best friend's smoking,
      explaining 38% of the variance in the total sample. Longitudinal regression
      analysis, however, showed that the beta coefficients of the smoking status of the
      best friend and friends in general were comparable to that of parental smoking.
      Parental smoking behavior was found to be as predictive of smoking onset after 1
      year as friends' smoking status.

PMID- 14572023
TI  - Vibrations in situ.

PMID- 14572024
TI  - LC-ESI-MS/MS draws the line on doping.

PMID- 14572025
TI  - Laser ablation-ICPMS.

PMID- 14572026
TI  - Lectins: proteins that interpret the sugar code.

PMID- 14572027
TI  - Seeing SAW potential.

PMID- 14572028
TI  - Infrared multiphoton dissociation with a hollow fiber waveguide.
AB  - A novel scheme for performing infrared multiphoton dissociation (IRMPD) is
      presented in which a hollow fiber waveguide (HFWG) is used to transmit IR
      radiation into the ion storage region of a mass spectrometer. Efficient
      dissociation of oligonucleotide and protein ions is demonstrated on an ESI-FTICR
      instrument in which IRMPD is performed in the external ion reservoir and on a
      quadrupole ion trap. Using a simple optical scheme consisting of a single
      focusing lens and an x, y translator, the 10.6-microm IR laser beam, initially
      3.5 mm in diameter, is focused into the vacuum-sealed HFWG. The small internal
      diameter and the high transfer efficiency of the waveguide allow IR radiation of
      high power density to be employed for IRMPD. In studies performed on a quadrupole
      ion trap, a 500-microm-i.d. waveguide was used as a medium to transmit IR
      radiation directly through a 700-microm orifice in the ring electrode. Efficient
      IRMPD of both a 12-mer oligonucleotide and the protein melittin were performed at
      laser powers of 0.5 and 3.2 W, respectively.

PMID- 14572029
TI  - Mechanism for the separation of large molecules based on radial migration in
      capillary electrophoresis.
AB  - We demonstrate a novel separation mechanism for large molecules based on their
      radial migration in capillary electrophoresis with applied hydrodynamic flow
      (HDF). The direction of radial migration depends on the direction of the applied
      HDF relative to the electric field. The radial migration velocities are size
      dependent, which could be attributed to the different degree of deformation under
      shear flow. Analytical separation was demonstrated on a sample plug containing
      lambda DNA (48 502 bp) and phiX174 RF DNA (5386 bp) with baseline separation.
      Alternatively, this separation mode can be performed continuously and is thus
      applicable to preparative separations. Without the need for gel/polymer or
      complex instrumentation, this separation technique is complementary to capillary
      gel electrophoresis and field-flow fractionation. Although large DNA molecules
      were used to demonstrate the separation mechanism here, these protocols could
      also be applied to the separation of proteins, cells, or particles based on size,
      shape, or deformability.

PMID- 14572030
TI  - A continuous-flow system for high-precision kinetics using small volumes.
AB  - A generally applicable continuous-flow kinetic analysis system that gives data of
      a precision high enough to measure small kinetic isotope effects for enzymatic
      and nonenzymatic reactions is described. It employs commercially available
      components that are readily assembled into an apparatus that is easy to use. It
      operates under laminar flow conditions, which requires that the time between the
      initiation of the reaction in the mixer and the observation be long enough that
      molecular diffusion can effect a symmetrization of the concentration profile that
      results from a thin plug of reagents introduced at the mixer. The analysis of a
      second-order irreversible reaction under pseudo-first-order conditions is
      presented. The Yersinia pestis protein tyrosine phosphatase catalyzed hydrolysis
      of p-nitrophenyl phosphate is characterized with the system, and a proton
      inventory on kcat is presented.

PMID- 14572031
TI  - Fast electrical lysis of cells for capillary electrophoresis.
AB  - In the past decade, capillary electrophoresis has demonstrated increasing utility
      for the quantitative analysis of single cells. New applications for the analysis
      of dynamic cellular properties demand sampling methods with sufficient temporal
      resolution to accurately measure these processes. In particular, intracellular
      signaling pathways involving many enzymes can be modulated on subsecond time
      scales. We have developed a technique to rapidly lyse an adherent mammalian cell
      using a single electrical pulse followed by efficient loading of the cellular
      contents into a capillary. Microfabricated electrodes were designed to create a
      maximum voltage drop across the flattened cell's plasma membrane at a minimum
      interelectrode voltage. The influence of the interelectrode distance, pulse
      duration, and pulse strength on the rate of cell lysis was determined. The
      ability to rapidly lyse a cell and collect and separate the cellular contents was
      demonstrated by loading cells with Oregon Green and two isomers of
      carboxyfluorescein. All three fluorophores were detected with a separation
      efficiency comparable to that of standards. Parallel comparison of electrical
      lysis to that produced by a laser-based lysis system revealed that the sampling
      efficiencies of the two techniques were comparable. Rapid cell lysis by an
      electrical pulse may increase the application of capillary electrophoresis to the
      study of cellular dynamics requiring fast sampling times.

PMID- 14572032
TI  - Spectroscopic features of dual fluorescence/luminescence resonance energy
      transfer molecular beacons.
AB  - Molecular beacons have the potential to become a powerful tool in gene detection
      and quantification in living cells. Here we report a novel dual molecular beacons
      approach to reduce false-positive signals in detecting target nucleic acids in
      homogeneous assays. A pair of molecular beacons, each containing a fluorescence
      quencher and a reporter fluorophore, one with a donor and a second with an
      acceptor fluorophore, hybridize to adjacent regions on the same target resulting
      in fluorescence resonance energy transfer (FRET). The detection of a FRET signal
      leads to a substantially increased signal-to-background ratio compared with that
      seen in single molecular beacon assays and enables discrimination between
      fluorescence due to specific probe/target hybridization and a variety of possible
      false-positive events. Further, when a lanthanide chelate is used as a donor in a
      dual-probe assay, extremely high signal-to-background ratios can be achieved
      owing to the long lifetime and sharp emission peaks of the donor and the time
      gated detection of acceptor fluorescence emission. These new approaches allow for
      the ultrasensitive detection of target molecules in a way that could be readily
      applied to real-time imaging of gene expression in living cells.

PMID- 14572033
TI  - Continuous monitoring of a restriction enzyme digest of DNA on a microchip with
      automated capillary sample introduction.
AB  - Continuous analysis of a DNA restriction enzyme digest on a microfabricated
      device is demonstrated with minimal intervention and enhanced time resolution. A
      62-base-pair fragment of dsDNA containing a KpnI site was used to demonstrate
      this process. A capillary was used to transfer sample from a single reaction mix
      to a microfabricated chip with parallel separation lanes. The 6
      carboxyfluorescein-labeled DNA fragments were detected with a CCD camera as they
      separated in the lanes, which were filled with linear polyacrylamide. The
      products of the restriction enzyme digest were monitored for up to 60 min at an
      average sampling rate of 1 injection/46 s, with consecutive injections as short
      as 1 injection/14 s. The digest was injected directly into the chip, eliminating
      the need for any sample-handling steps after addition of the enzyme to the
      reaction mix. The effects of temperature and restriction enzyme concentration
      were briefly examined, as well. This work shows the potential of this method to
      provide valuable information about the process of restriction enzyme cleavage.

PMID- 14572034
TI  - Characterization of the acid/base and redox chemistry of phytochelatin analogue
      peptides.
AB  - The phytochelatins are a family of polydisperse, thiol-rich peptides that are
      synthesized by plants in response to exposure to heavy metals. The amino acid
      sequence of the phytochelatin peptides is (gamma-glutamyl-cysteinyl)n-glycine,
      where n typically ranges from 2 to 5. In the first phase of a program to
      characterize the coordination chemistry of the phytochelatins with heavy metals,
      the phytochelatin analogue peptides acetyl(gamma-glutamyl-cysteinyl)n-glycine
      amide (Ac-(gamma-Glu-Cys)n-NH2, n = 2-6) have been synthesized by solid-phase
      peptide synthesis methods and characterized by 1H NMR spectroscopy. The 1H NMR
      spectra of the analogue peptides were completely assigned by using band-selective
      homonuclear-decoupled (BASHD) two-dimensional NMR experiments to achieve spectral
      resolution. The acid dissociation constant of each cysteine residue in each
      peptide was determined from chemical shift-pH titration data for the CalphaH
      protons of the cysteine residues. The resonances for the CalphaH protons were
      resolved in BASHD-total correlation spectroscopy spectra that were measured as a
      function of pH. The pKA values for a given thiol group depend on the position of
      the cysteine residue in the sequence, with the thiol group of the cysteine
      residue attached to the C-terminal glycine being the most acidic. The pKA values
      also depend on the size of the peptide, increasing as the size, and thus the
      negative charge, of the peptide increases. The redox potential for oxidation of
      the two thiol groups of Ac(gamma-Glu-Cys)2-NH2 to form an intramolecular
      disulfide bond was also determined by measuring the equilibrium constant for its
      thiol/disulfide exchange reaction with glutathione.

PMID- 14572035
TI  - Use of capillary electrophoresis and endogenous fluorescent substrate to monitor
      intracellular activation of protein kinase A.
AB  - Here we demonstrate for the first time the use of an endogenous
      multiphosphorylatable substrate for monitoring the intracellular activation of
      kinase with capillary electrophoresis. First, we devised a novel PCR-based
      strategy for controlled generation of short multirepeat DNA sequences and applied
      this method to generate a green fluorescence protein (GFP)-tagged protein
      substrate containing eight phosphorylation sites for protein kinase A (PKA). The
      protein substrate was transiently expressed in C2C12 rat myoblast cells, and
      intracellular PKA was then activated by adding [8]-bromo-cyclic AMP to the cell
      culture medium. Phosphorylated product and nonphosphorylated substrate present in
      the crude cell extract were separated by capillary zone electrophoresis and
      detected with laser-induced fluorescence of the GFP tag. The identities of two
      electrophoretic peaks were confirmed by both phosphorylation of the substrate and
      dephosphorylation of the product in vitro. The proposed method was applied to
      monitoring the activation of PKA in single myoblast cells. It advantageously
      allowed us to avoid microinjection of the substrate, the procedure that is both
      hard to perform and excessively invasive when applied to small mammalian cells.

PMID- 14572036
TI  - An identification method for altered proteins in tissues utilizing fluorescence
      derivatization, liquid chromatography, tandem mass spectrometry, and a database
      searching algorithm.
AB  - Two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) is now widely used
      as a tool for proteomic studies. For the sensitive determination of proteins in
      2D-PAGE, fluorescence derivatization of primary amino moieties of proteins with
      cyanine dyes was recently developed. However, precipitation of the proteins could
      occur if completely derivatized because of the lower solubility of the resultant
      derivatives owing to the hydrophobicity of the reagents and the loss of the
      hydrophilic primary amino moieties. Thus, in this paper, a water-soluble and
      thiol-specific fluorogenic reagent, ammonium 7-fluoro-2,1,3-benzoxadiazole-4
      sulfonate, was adopted for the derivatization of proteins in tissues either with
      and without stimulation. Then, the method follows a separation of the derivatives
      by liquid chromatography with fluorescence detection, an isolation of only the
      altered proteins, an enzymatic digestion of the isolated proteins, and an
      identification of the proteins by liquid chromatography/MS/MS with the database
      searching algorithm. By using this method, we identified the altered expressions
      of five increased proteins (e.g., pancreatic polypeptide) as well as three
      decreased proteins (e.g., insulin 2) in the islets of Langerhans in Wistar rats 2
      days after they were subcutaneously administered with dexamethasone.

PMID- 14572037
TI  - Determination of carbamazepine and its metabolites in aqueous samples using
      liquid chromatography-electrospray tandem mass spectrometry.
AB  - A quantitative method is described for solid-phase extraction (SPE) followed by
      liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the simultaneous
      analysis of carbamazepine and its five metabolites, 10,11-dihydro-10,11
      epoxycarbamazepine, 10,11-dihydro-10,11-dihydroxycarbamazepine, 2
      hydroxycarbamazepine, 3-hydroxycarbamazepine, and 10,11-dihydro-10
      hydroxycarbamazepine. An SPE procedure was used to concentrate target compounds
      from aqueous samples collected from sewage treatment plant (STP) wastewater and
      surface water. Extracts were analyzed using electrospray LC-MS/MS with time
      scheduled selected reaction monitoring. The recoveries of the analytes were 83.6
      102.2% from untreated sewage (influent), 90.6-103.5% from treated sewage
      (effluent), and 95.7-102.9% from surface water samples. The instrumental
      detection limits were 0.8-4.8 pg for the analytes. Matrix effects were
      investigated for the analytes in HPLC-grade water, surface water, and STP
      influent and effluent. Ion suppression increased for analytes in order of surface
      water to STP effluent to STP influent, but no ion suppression was observed for
      analytes in HPLC-grade water. The developed method was validated by analysis of
      environmental aqueous samples: STP influent and effluent and surface water.
      Carbamazepine and all five metabolites were detected in STP influent and effluent
      samples. Only carbamazepine and 10,11-dihydro-10,11-dihydroxycarbamazepine were
      detected in the surface water sample. Notably, 10,11-dihydro-10,11
      dihydroxycarbamazepine was detected at approximately 3 times higher
      concentrations than the parent drug, carbamazepine, in all of the aqueous
      samples. To our knowledge, this is the first report on the simultaneous
      determination of carbamazepine and its metabolites in environmental samples.

PMID- 14572038
TI  - Analysis of volatile organic compounds in air with a micro ion trap mass
      analyzer.
AB  - Analysis of several volatile organic compounds in air has been demonstrated with
      a micro ion trap mass analyzer equipped with a semipermeable membrane sampling
      inlet. MS/MS of selected compounds was also shown to be feasible with the
      miniature ion trap and could be used to improve sensitivity by reducing
      background noise.

PMID- 14572039
TI  - Quantitative characterization of a polystyrene/poly(alpha-methylstyrene) blend by
      MALDI mass spectrometry and size-exclusion chromatography.
AB  - The use of coupled size-exclusion chromatography and MALDI mass spectrometry for
      quantitative measurement of the composition of technical polymer blends at the
      molecular level is described. The method is illustrated with a model binary blend
      consisting of polystyrene and poly(alpha-methylstyrene), both polymers having
      similar molecular weights and polydispersities. The proposed MALDI data treatment
      allows determination of the chemical composition of the blend, the molecular
      weights of the constituents, and the distributions of the homopolymers.

PMID- 14572040
TI  - Capillary high-performance liquid chromatography/mass spectrometric analysis of
      proteins from affinity-purified plasma membrane.
AB  - Proteomics analysis of plasma membranes is a potentially powerful strategy for
      the discovery of proteins involved in membrane remodeling under diverse cellular
      environments and identification of disease-specific membrane markers. A key
      factor for successful analysis is the preparation of plasma membrane fractions
      with low contamination from subcellular organelles. Here we report the
      characterization of plasma membrane prepared by an affinity-purification method,
      which involves biotinylation of cell-surface proteins and subsequent affinity
      enrichment with strepavidin beads. Western blotting analysis showed this method
      was able to achieve a 1600-fold relative enrichment of plasma membrane versus
      mitochondria and a 400-fold relative enrichment versus endoplasmic reticulum, two
      major contaminants in plasma membrane fractions prepared by conventional
      ultracentrifugation methods. Capillary-HPLC/MS analysis of 30 microg of affinity
      purified plasma membrane proteins led to the identification of 918 unique
      proteins, which include 16.4% integral plasma membrane proteins and 45.5% cytosol
      proteins (including 8.6% membrane-associated proteins). Notable among the
      identified membrane proteins include 30 members of ras superfamily, receptors
      (e.g., EGF receptor, integrins), and signaling molecules. The low number of
      endoplasmic reticulum and mitochondria proteins (approximately 3.3% of the total)
      suggests the plasma membrane preparation has minimum contamination from these
      organelles. Given the importance of integral membrane proteins for drug design
      and membrane-associated proteins in the regulation cellular behaviors, the
      described approach will help expedite the characterization of plasma membrane
      subproteomes, identify signaling molecules, and discover therapeutic membrane
      protein targets in diseases.

PMID- 14572041
TI  - High-efficiency, two-dimensional separations of protein digests on microfluidic
      devices.
AB  - High-efficiency, two-dimensional separations of tryptic digests were achieved
      using glass microfluidic devices. Following micellar electrokinetic
      chromatography (MEKC) separations in a 19.6-cm-long serpentine channel, the
      peptides were rapidly sampled into a 1.3-cm-long second-dimension channel, where
      they were separated by capillary electrophoresis (CE). The turns in the
      serpentine channel were asymmetrically tapered to minimize geometrical
      contributions to band broadening and to provide ample channel length for high
      efficiency chromatographic separations. Analysis of rhodamine B injections
      routinely produced plate numbers of 230000 and 40000 in the first (MEKC) and
      second (CE) dimensions, respectively, corresponding to plate heights of 0.9 and
      0.3 microm. The electric field strengths were 200 V/cm for MEKC and 2400 V/cm for
      CE. In analysis times less than 15 min, two-dimensional separation of bovine
      serum albumin tryptic digest produced a peak capacity of 4200 (110 in the first
      dimension and 38 in the second dimension). The system was used to identify a
      peptide from a tryptic digest of ovalbumin using standard addition and to
      distinguish between tryptic digests of human and bovine hemoglobin.

PMID- 14572042
TI  - Identification of water-soluble selenium-containing proteins in selenized yeast
      by size-exclusion-reversed-phase HPLC/ICPMS followed by MALDI-TOF and
      electrospray Q-TOF mass spectrometry.
AB  - An approach to speciation of selenium incorporated in yeast proteins was
      developed. The tryptic digest of a water-soluble protein fraction isolated by
      size-exclusion chromatography was analyzed by reversed-phase HPLC/ICPMS. The
      selenopeptides selected owing to the detector's elemental specificity were then
      analyzed by MALDI-TOFMS in order to select target ions for collision-induced
      dissociation MS. The latter, carried out with an electrospray Q-TOF spectrometer,
      enabled the sequencing of the selenopeptides detected by HPLC/ICPMS. The approach
      allowed for the first time the identification of a family of Se-containing
      proteins resulting from the replacement by selenomethionine of 2-9 methionine
      residues in a salt-stress-induced protein SIP18 (Mr 8874). The presence of these
      proteins was confirmed by MALDI-TOFMS of the original (nondigested) protein
      fraction. Another selenium protein identified was a heat-shock protein HSP12 (Mr
      11693) in which the only methionine residue was replaced by selenomethionine.
      These two Se-containing proteins accounted for more than 95% of selenium in the
      water-soluble protein fraction.

PMID- 14572043
TI  - Imaging of L-glutamate fluxes in mouse brain slices based on an enzyme-based
      membrane combined with a difference-image analysis.
AB  - A time-resolved imaging method for visualizing L-glutamate release in mammalian
      brain slices is proposed by using an enzyme membrane combined with a difference
      image analysis. The enzyme membrane is composed of L-glutamate oxidase and
      horseradish peroxidase incorporated into a bovine serum albumin matrix. L
      Glutamate triggers an enzyme-coupling reaction to convert a redox substrate (DA
      64) to Bindschedler's Green, which gives a green color signal. The difference
      image analysis is based on calculating slopes of a signal versus time (t) plot in
      the time range from (t - 40 s) to (t + 40 s) for visualizing L-glutamate release
      in terms of its flux (in mol min(-1) cm(-2)). The method was applied to a time
      resolved imaging of hippocampal distribution of ischemia-induced L-glutamate
      release in mouse brain slices. The image of L-glutamate distribution showed that
      the level and time courses of L-glutamate fluxes were neuronal region-dependent.
      The maximum flux of L-glutamate at CA1 was observed at 7.7 min after ischemia.
      The flux at 7.7 min increased in the order of CA1 approximately CA3 > DG. The
      time course of the L-glutamate flux in the CA1 region was biphasic and that in
      the DG region was modestly biphasic. In the CA3 region, such biphasic release of
      L-glutamate was not seen. The ischemia-induced L-glutamate flux was accelerated
      when Mg2+ was omitted from an extracellular solution. The present enzyme membrane
      based approach provides a useful method for visualizing distribution of L
      glutamate release in the brain slices during ischemia.

PMID- 14572044
TI  - Ratiometric optical PEBBLE nanosensors for real-time magnesium ion concentrations
      inside viable cells.
AB  - This paper presents the development and characterization of a highly selective
      magnesium fluorescent optical nanosensor, made possible by PEBBLE (probe
      encapsulated by biologically localized embedding) technology. A ratiometric
      sensor has been developed by co-immobilizing a dye that is sensitive to and
      highly selective for magnesium, with a reference dye in a matrix. The sensors are
      prepared via a microemulsion polymerization process, which entraps the sensing
      components inside a polymer matrix. The resultant spherical sensors are
      approximately 40 nm in diameter. The Coumarin 343 (C343) dye, which by itself
      does not enter the cell, when immobilized in a PEBBLE is used as the magnesium
      selective agent that provides the high and necessary selectivity over other
      intracellular ions, such as Ca2+, Na+, and K+. The dynamic range of these sensors
      was 1-30 mM, with a linear range from 1 to 10 mM, with a response time of <4 s.
      In contrast to free dye, these nano-optodes are not perturbed by proteins. They
      are fully reversible and exhibit minimal leaching and photobleaching over
      extended periods of time. In vitro intracellular changes in Mg2+ concentration
      were monitored in C6 glioma cells, which remained viable after PEBBLE delivery
      via gene gun injection. The selectivity for Mg2+ along with the biocompatibility
      of the matrix provides a new and reliable tool for intracellular magnesium
      measurements.

PMID- 14572045
TI  - A hypergeometric probability model for protein identification and validation
      using tandem mass spectral data and protein sequence databases.
AB  - We present a new probability-based method for protein identification using tandem
      mass spectra and protein databases. The method employs a hypergeometric
      distribution to model frequencies of matches between fragment ions predicted for
      peptide sequences with a specific (M + H)+ value (at some mass tolerance) in a
      protein sequence database and an experimental tandem mass spectrum. The
      hypergeometric distribution constitutes null hypothesis-all peptide matches to a
      tandem mass spectrum are random. It is used to generate a score characterizing
      the randomness of a database sequence match to an experimental tandem mass
      spectrum and to determine the level of significance of the null hypothesis. For
      each tandem mass spectrum and database search, a peptide is identified that has
      the least probability of being a random match to the spectrum and the
      corresponding level of significance of the null hypothesis is determined. To
      check the validity of the hypergeometric model in describing fragment ion
      matches, we used chi2 test. The distribution of frequencies and corresponding
      hypergeometric probabilities are generated for each tandem mass spectrum. No
      proteolytic cleavage specificity is used to create the peptide sequences from the
      database. We do not use any empirical probabilities in this method. The scores
      generated by the hypergeometric model do not have a significant molecular weight
      bias and are reasonably independent of database size. The approach has been
      implemented in a database search algorithm, PEP_PROBE. By using a large set of
      tandem mass spectra derived from a set of peptides created by digestion of a
      collection of known proteins using four different proteases, a false positive
      rate of 5% is demonstrated.

PMID- 14572046
TI  - A 15-s protein separation employing hydrodynamic force on a microchip.
AB  - We report here a novel pressurization technique for microchip electrophoresis
      that enables 15-s separation of protein mixtures extracted from biological
      samples. Although pressure-driven flow is usually parabolic flow, pressurization
      prior to electrophoresis separation produced a plug flow and achieved a dramatic
      migration time reduction without compromising resolution. Sample plugs were
      pushed forward by pressurization after loading the sample but before
      electrophoresis separation, in the absence of an electric potential. Higher
      pressures enabled higher speed separation; furthermore, the resolution could be
      easily controlled using an optimal pressure. In addition, the slow medium
      pressurization technique enabled 2-D separation in only a single channel on a
      microchip. Utilizing this technique, 12 samples of complex protein mixture
      extracted from a human T lymphoblastic cell line, Jurkat cells, were separated
      within 15 s in a single run using a 12-microchannel array. In addition, target
      proteins from Jurkat cells were detected within this time. This novel
      pressurization technique on a microchip will offer enormous advantages for
      proteome analysis over commonly used 2-D electrophoresis.

PMID- 14572047
TI  - Quantifying trace elements in individual aquatic protist cells with a synchrotron
      X-ray fluorescence microprobe.
AB  - The study of trace metal cycling by aquatic protists is limited by current
      analytical techniques. Standard "bulk" element analysis techniques that rely on
      physical separations to concentrate cells for analysis cannot separate cells from
      co-occurring detrital material or other cells of differing taxonomy or trophic
      function. Here we demonstrate the ability of a synchrotron-based X-ray
      fluorescence (SXRF) microprobe to quantify the elements Si, Mn, Fe, Ni, and Zn in
      individual aquatic protist cells. This technique distinguishes between different
      types of cells in an assemblage and between cells and other particulate matter.
      Under typical operating conditions, the minimum detection limits are 7.0 x 10(
      16) mol microm(-2) for Si and between 5.0 x 10(-20) and 3.9 x 10(-19) mol microm(
      2) for Mn, Fe, Ni, and Zn; this sensitivity is sufficient to detect these
      elements in cells from even the most pristine waters as demonstrated in
      phytoplankton cells collected from remote areas of the Southern Ocean. Replicate
      analyses of single cells produced variations of <5% for Si, Mn, Fe, and Zn and
      <10% for Ni. Comparative analyses of cultured phytoplankton cells generally show
      no significant differences in cellular metal concentrations measured with SXRF
      and standard bulk techniques (spectrophotometry and graphite furnace atomic
      absorption spectrometry). SXRF also produces two-dimensional maps of element
      distributions in cells, thereby providing information not available with other
      analytical approaches. This technique enables the accurate and precise
      measurement of trace metals in individual aquatic protists collected from natural
      environments.

PMID- 14572048
TI  - Microorganism identification by matrix-assisted laser/desorption ionization mass
      spectrometry and model-derived ribosomal protein biomarkers.
AB  - An improved data analysis method is described for rapid identification of intact
      microorganisms from MALDI-TOF-MS data. The method makes no use of mass spectral
      fingerprints. Instead, a microorganism database is automatically generated that
      contains biomarker masses derived from ribosomal protein sequences and a model of
      N-terminal Met loss. We quantitatively validate the method via a blind study that
      seeks to identify microorganisms with known ribosomal protein sequences. We also
      include in the database microorganisms with incompletely known sets of ribosomal
      proteins to test the specificity of the method. With an optimal MALDI protocol,
      and at the 95% confidence level, microorganisms represented in the database with
      20 or more biomarkers (i.e., those with complete or nearly completely sequenced
      genomes) are correctly identified from their spectra 100% of the time, with no
      incorrect identifications. Microorganisms with seven or less biomarkers (i.e.,
      incompletely sequenced genomes) are either not identified or misidentified.
      Robustness with respect to variations in sample preparation protocol and mass
      analysis protocol is demonstrated by collecting data with two different matrixes
      and under two different ion-mode configurations. Statistical analysis suggests
      that, even without further improvement, the method described here would
      successfully scale up to microorganism databases with roughly 1000
      microorganisms. The results demonstrate that microorganism identification based
      on proteome data and modeling can perform as well as methods based on mass
      spectral fingerprinting.

PMID- 14572049
TI  - Analysis of high-density lipoprotein apolipoproteins recovered from specific
      immobilized pH gradient gel pI domains by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry.
AB  - The proteins associated with the circulating lipoproteins in the blood function
      not only for mediating lipid metabolism but also for maintaining structural
      stability of the micellelike structure. Any modifications of these proteins, by
      mutation or posttranslational modification, could compromise the function of
      these proteins and contribute to the development of cardiovascular disease.
      Because of the presence of extensive lipophilic domains, these proteins, when
      recovered from the lipoprotein particle (apolipoproteins) present an analytical
      challenge because of low solubility and proclivity toward aggregate formation.
      Our goal is to characterize these proteins by a combination of high-accuracy pI
      measurement coupled with MALDI analysis. In this report, we demonstrate the high
      resolution of immobilized pH gradient isoelectric focusing (IPG-IEF) for the
      analysis of these apolipoproteins isolated from serum HDL collected from a
      density gradient ultracentrifugation-based separation. The IPG separation of the
      HDL apolipoproteins was imaged and combined with digital analysis to produce a
      detailed pI profile of the apolipoproteins in the high-density lipoprotein (HDL)
      fraction. This is the first time that a high-resolution pI profile has been
      obtained for the HDL apolipoproteins. The feasibility of linking the pI profile
      to a MALDI-based molecular weight determination was achieved by incorporating
      passive elution of the intact proteins from the IPG gel with a four-component
      solvent mixture that solved the problem of recovery of the apolipoproteins from
      the IPG matrix. Twenty-five bands were observed in the pI profile. A survey
      analysis of 12 of these bands by MALDI indicated that they were associated with
      the known HDL apolipoproteins. While there is considerable overlap in the pI
      profiles of the apolipoproteins, linking the analysis with a MALDI-based second
      dimension in m/z is shown to be an efficient method to characterize this complex
      mixture of apolipoproteins.

PMID- 14572050
TI  - Grazing exit electron probe microanalysis of submicrometer inclusions in metallic
      materials.
AB  - Grazing exit electron probe microanalysis (GE-EPMA) is a new method of EPMA in
      which characteristic X-rays emitted from only near-surface regions of a specimen
      are detected at extremely low exit angles near 0 degrees (the grazing exit
      condition). This technique requires the analytical objects exist on a flat
      surface. Therefore, the GE-EPMA analysis has been used only for the analysis of
      particles or a thin film on a flat substrate so that there were only few
      applications for practical analysis. As a new application, we have carried out GE
      EPMA analysis of approximately 0.2-microm inclusions on stainless steel, which
      appeared to be a projection on the specimen surface with chemical etching. The GE
      EPMA quantitative results were in excellent agreement with those of inclusions
      that were extracted from the stainless steel and analyzed by EPMA with
      conventional exit condition (30 degrees). This method could be, therefore,
      applied to the analysis of the submicrometer inclusion in a wide variety of
      metallic materials if the inclusion appears to be a projection with chemical
      etching treatment.

PMID- 14572051
TI  - Mono- and multilayer formation by diazonium reduction on carbon surfaces
      monitored with atomic force microscopy "scratching".
AB  - Contact mode atomic force microscopy (AFM) was used to intentionally scratch a
      monolayer deposited on a pyrolyzed photoresist film (PPF). The force was set to
      completely remove the monolayer but not to damage the underlying PPF surface. A
      line profile determined across the scratch with tapping mode AFM permitted
      determination of the monolayer thickness from the depth of the scratch. A
      statistical process was devised to avoid user bias in determining the monolayer
      thickness and was used to determine the thickness as a function of derivatization
      parameters. PPF surfaces modified by reduction of diazonium ions of stilbene,
      biphenyl, nitrobiphenyl, terphenyl, and nitroazobenzene (NAB) were scratched and
      their modification layer thicknesses determined. For single-scan derivatizations
      of 1 mM diazonium ions to -0.6 V versus Ag+/Ag, the biphenyl and stilbene
      monolayers exhibited thicknesses close to those expected for true monolayers.
      However, more extensive derivatization resulted in multilayers up to 6.3 nm thick
      for the case of NAB. Such multilayers imply that electrons are transmitted
      through the growing film during diazonium reduction, despite the fact that
      electron tunneling would not be expected to be operative over such long
      distances. The results are consistent with a conductance increase in the growing
      film, which yields a partially conductive layer that can support further
      diazonium ion reduction and additional layer growth.

PMID- 14572052
TI  - Electronic detection of target nucleic acids by a 2,6-disulfonic acid
      anthraquinone intercalator.
AB  - A DNA hybridization biosensor based on long-range electron transfer that is
      capable of detecting DNA single-base mismatch is presented. A mixed self
      assembled monolayer of single-stranded DNA (ss-DNA), thiolated at the 3' end, and
      6-mercapto-1-hexanol was formed on a gold surface. This probe ss-DNA-modified
      gold surface was incubated in 2,6-disulfonic acid anthraquinone (AQDS)
      intercalator solution, rinsed, and placed in an AQDS-free buffer solution,
      whereupon voltammetric experiments were performed. No voltammetric peaks were
      observed for probe ss-DNA-modified gold electrodes. Upon DNA hybridization and
      incubation in AQDS, clear voltammetric peaks, consistent with the oxidation and
      reduction of AQDS, were observed. The absence of AQDS electrochemistry for ss-DNA
      modified surfaces clearly shows the electrochemistry is due to long-range
      electron transfer through the DNA duplex. No peak currents were observed when the
      probe ss-DNA-modified surface was exposed to noncomplementary target DNA, but
      there was a diminution in current signal upon hybridization with C-A mismatched
      and a G-A mismatched targets.

PMID- 14572053
TI  - A dry process for production of microfluidic devices based on the lamination of
      laser-printed polyester films.
AB  - A new microfabrication process based on a xerographic process is described. A
      laser printer is used to selectively deposit toner on a polyester film, which is
      subsequently laminated against another polyester film. The toner layer binds the
      two polyester films and allows the blank regions to become channels for
      microfluidics. These software-outlined channels are approximately 6 microm deep.
      Approximately twice this depth is obtained by laminating two printed films. The
      resulting devices were not significantly damaged after 24 h of exposure to
      aqueous solutions of H3PO4, NaOH, methanol, acetonitrile, or sodium dodecyl
      sulfate. Electric tests with an impedance analyzer and microchannels filled with
      KCl solution demonstrated that (1) wide channels suffer from deformation of the
      top and bottom walls due to the lamination of the polyester films and (2) the
      toner walls are somewhat porous. Although these drawbacks limit the maximum width
      of a channel and the minimum distance between two channels, the process is an
      attractive option to other expensive, laborious, and time-consuming methods for
      microchannels fabrication. The process has been used to implement devices for
      electrospray tip and capillary electrophoresis with contactless conductivity
      detection.

PMID- 14572054
TI  - Simultaneous determination of tryptophan and glutathione in individual rat
      hepatocytes by capillary zone electrophoresis with electrochemical detection at a
      carbon fiber bundle--Au/Hg dual electrode.
AB  - A method for single-cell analysis was developed by combining capillary zone
      electrophoresis (CZE) with electrochemical detection (ECD) using a dual electrode
      consisting of two different types of electrode material (carbon fiber and Au/Hg).
      In this method, the parallel mode was used. Different potentials were applied to
      both electrodes of the dual electrode. Tryptophan and glutathione, which could
      not be simultaneously detected by normal CZE-ECD, could be simultaneously and
      selectively detected by CZE-ECD at the dual electrode in one run, respectively.
      The CZE-ECD system with the dual electrode was applied to determine them in
      individual rat hepatocytes.

PMID- 14572055
TI  - Improving the detection limit of anion-selective electrodes: an iodide-selective
      membrane with a nanomolar detection limit.
AB  - The lower detection limit and the selectivity behavior of anion-selective
      electrodes (ISEs) are improved by using optimized inner solutions and membrane
      compositions. With a membrane based on the recently described ionophore
      [9]mercuracarborand-3, a detection limit of 2 x 10(-9) M has been achieved for
      iodide. Nevertheless, the improvements are less pronounced than in the case of
      cation ISEs. This is mainly due to the fact that so far no anion ISE is known
      with the extremely high selectivities of cation ISEs. If the membrane does not
      contain an ionophore, leaching of the ion exchanger from the membrane into the
      sample is also a relevant limiting factor except for ion exchangers of very high
      lipophilicity.

PMID- 14572056
TI  - Layered double hydroxides: an attractive material for electrochemical biosensor
      design.
AB  - Electrochemical biosensors for phenol determination were developed based on the
      immobilization of polyphenol oxidase (PPO) within two different clay matrixes,
      one anionic (layered double hydroxide, LDH) and the other cationic (Laponite).
      The biosensor based on the enzyme immobilized in [Zn-Al-Cl] LDH shows greater
      sensitivity (7807 mA M(-1) cm(-2)) and maximum current (492 microA cm(-2)).
      Biosensor characteristics, such as Michaelis-Menten constant, recycling constant,
      activation energy, and permeability highlight the advantages of LDH matrixes to
      immobilize PPO. It appears that LDH provides a favorable environment to PPO
      activity. The best PPO/[Zn-Al-Cl] configuration was used to determine five
      different phenol derivatives reaching extremely sensitive detection limits (< or
      = 1 nM).

PMID- 14572057
TI  - Scanning electrochemical microscopy. 48. Hg/Pt hemispherical
      ultramicroelectrodes: fabrication and characterization.
AB  - Hg/Pt hemispherical ultramicroelectrodes (UMEs) (25-microm diameter) were
      prepared either by electrodeposition from a mercuric ion solution or by simple
      contact of the Pt disk to a hanging mercury drop electrode. The two methods
      produced equivalent tips. Optical inspection and electrochemical characterization
      of these Hg tips with methyl viologen, cobalt sepulchrate trichloride, and
      hexamineruthenium(III) chloride confirm the hemispherical nature of the UME. The
      scanning electrochemical microscopy approach curves for all three redox couples
      over a conductive substrate fit theoretical plots for hemispherical electrodes.
      The numerical solution of the diffusion equations for substrate generation-tip
      collection (SG-TC) transients for a finite Pt disk and Hg/Pt hemispherical UME
      are reported and compared to experimental results. A diffusion layer
      approximation is presented, and diffusion coefficients are extracted from the
      simulation. The SG-TC results reveal the enhanced sensitivity of hemispherical
      UME to radial diffusion.

PMID- 14572058
TI  - Immobilized enzyme-linked DNA-hybridization assay with electrochemical detection
      for Cryptosporidium parvum hsp70 mRNA.
AB  - An electrochemical enzyme-linked immobilized DNA-hybridization assay for the
      detection of Cryptosporidium parvum in water has been developed. The target
      molecule was a 121-nucleotide sequence from the C. parvum heat shock protein 70
      (hsp70 mRNA from U71181 gene). This analyte offers the possibility of
      distinguishing dead from live oocysts. The assay involves covalent attachment of
      a primary DNA probe via its 5'-amine-terminus to self-assembled monolayers of
      mercaptoundecanoic acid to a gold surface. The primary DNA probe was used to
      capture the target (sequence 1039-1082 of U71181 gene for the mRNA), by
      hybridization to a 20-base complementary sequence on the target (at sequence 1063
      1082). A secondary DNA probe labeled with alkaline phosphatase (AP) was then
      hybridized to base sequence 1039-1062 on the target. p-Aminophenol, which is
      enzymatically generated by the immobilized AP from p-aminophenyl phosphate
      (PAPP), is detected using electrochemistry. The peak current of cyclic
      voltammograms from a PAPP solution, in which gold-coated silicon wafer modified
      with the complete assembly of the assay components was incubated, is linear with
      concentration of the target (5-50 microg/mL, where P1 and P2-AP concentrations
      are 50 microg/mL). A detection limit of 2 microg/mL (or 146 nM) of the DNA target
      was obtained. Cross-reactivity tests showed high selectivity for heat-shocked C.
      parvum. No signal was obtained for either the synthetic DNA for hsp70 of
      Campylobacter lari, Escherichia coli, Giardia lamblia, Salmonella typhimurium,
      and Listeria monocytogenes or for the products of heat-shocked whole organisms of
      E. coli, G. lamblia, Staphylococcus aureus, and Cryptosporidium muris.

PMID- 14572059
TI  - Amperometric sensing at high temperature with a "wired" thermostable glucose-6
      phosphate dehydrogenase from Aquifex aeolicus.
AB  - An amperometric enzyme sensor capable of operating at high temperatures was
      developed by utilizing a "wired" thermostable glucose-6-phosphate dehydrogenase
      (tG6PDH) from the hyperthermophilic bacterium Aquifex aeolicus. The response of
      the system was monitored through detection of the product of the enzymatic
      reaction, NADH, which was electrocatalytically reoxidized to NAD by a
      thermostable redox mediator, osmium (1,10-phenanthroline-5,6-dione)2-poly(4
      vinylpyridine), at Eapp = +150 mVvs Ag/AgCl/KClsat. The enzyme was "wired" onto
      the surface of graphite electrodes by using an epoxy-based poly(ethylene glycol)
      diglycidyl ether cross-linker. The stability of the sensor at higher temperatures
      clearly surpassed the conventional system utilizing a mesophilic G6PDH (mG6PDH)
      from Leuconostoc mesenteroides. The mG6PDH-based system lost 26% of its response
      after 20 min at 50 degrees C. The response of the tG6PDH-based system remained
      unchanged under the same conditions. The tG6PDH-based system demonstrated
      excellent stability up to a temperature of 83 degrees C.

PMID- 14572060
TI  - Voltammetric procedure for examining DNA-modified surfaces: quantitation,
      cationic binding activity, and electron-transfer kinetics.
AB  - To examine DNA-modified surfaces, we have developed a simple, convenient, and
      reliable procedure based on the voltammetric response of multiply charged
      transition metal cations (such as [Ru(NH3)6]3+) bound electrostatically to the
      DNA probes. At micromolar concentrations of the redox molecules in the
      electrolyte, the reduction and oxidation waves resulting from the immobilized
      cations on DNA-modified electrodes are well defined, stable, and reproducible.
      The surface densities of both single- and double-stranded oligonucleotides were
      accurately determined by integration of the peak for reduction of [Ru(NH3)6]3+ to
      [Ru(NH3)6]2+. In addition, the binding constant and electron-transfer rate
      constant of [Ru(NH3)6]3+ on DNA-modified electrodes were evaluated with the help
      of classical models. The present research provides not only an applicable and
      simple protocol for the quantitation of DNA probes on chips but also a versatile
      and powerful tool for the investigation of the binding activity and electron
      transfer kinetics of cationic analytes on DNA-modified surfaces.

PMID- 14572061
TI  - 3,3',5,5'-tetramethyl-N-(9-anthrylmethyl)benzidine: a dual-signaling fluorescent
      reagent for optical sensing of aliphatic aldehydes.
AB  - A new optical chemical sensor for continuous monitoring of aliphatic aldehydes
      has been proposed based on the reversible chemical reaction between a new sensing
      reagent, 3,3',5,5'-tetramethyl-N-(9-anthrylmethyl)benzidine (TMAB), and the
      analytes. TMAB, containing two receptors and two fluorescent reporters, can
      perform dual fluorescence responses corresponding to the reactions of hydrogen
      ion and carbonyl compound. When immobilized in a plasticized poly(vinyl chloride)
      membrane, TMAB extracts aliphatic aldehydes from aqueous solution into the bulk
      membrane phase and reacts with the analyte by forming a Schiff base. Since the
      extraction equilibrium and chemical reaction are accompanied by fluorescence
      increase of the sensing membrane, the chemical recognition process could be
      directly translated into an optical signal. At pH 3.20, the sensor exhibits a
      dynamic detection range from 0.017 to 4.2 mM n-butyraldehyde with a limit of
      detection of 0.003 mM. The forward response time (t95) of the sensor is 3-5 min,
      and the reverse response time is 5-7 min. The responses of the sensor toward
      different kinds of aldehydes and ketones depend on the lipophilicity and the
      reactivity of the analytes. Since the fluorescence enhancement of the sensing
      membrane at 296 nm/410 nm is only related to the formation of Schiff base, the
      measurement of aldehydes is independent of pH.

PMID- 14572062
TI  - Photonic crystal optrode sensor for detection of Pb2+ in high ionic strength
      environments.
AB  - We developed an optrode sensing device that utilizes a polymerized colloidal
      array (PCCA) photonic crystal material. This array diffracts light in the visible
      spectral region due to the periodic spacing of colloidal particles. The PCCA
      changes diffraction wavelength due to binding of Pb2+ to an 18-crown-6 ether
      molecular recognition agent. This optrode consists of a probe assembly that
      contains the PCCA Pb2+ sensing film. An inexpensive, commercial diode array
      spectrometer and a fiber-optic reflectance probe monitors the wavelength of light
      back diffracted by the PCCA. Liquid inlet and outlet connections are provided to
      introduce the sample solution and to exchange out nonbinding ions. In low ionic
      strength solutions, diffraction wavelength shifts are actuated by the binding of
      the Pb2+ to the crown ether to immobilize the Pb2+ counterions. In these low
      ionic strength solutions, a Donnan potential forms to cause an osmotic pressure,
      which swells the PCCA in proportion to the number density of bound Pb2+. This
      Donnan potential disappears at high ionic strengths. Thus, no response of the
      PCCA occurs. Our optrode design allows for the fast removal of nonbound ions from
      the PCCA by washing with pure water. Since the bound Pb2+ ions have a slow off
      rate from the crown ether, the bound Pb2+ PCCA diffraction transiently red shifts
      during washing, directly in proportion to the sample Pb2+ concentration. This
      transient diffraction red-shift can be used to quantitatively determine Pb2+
      concentrations in high ionic strength solutions such as bodily fluids.

PMID- 14572063
TI  - A nanoinjector for microanalysis.
AB  - We describe a simple miniature injection device that can be used for introduction
      of nanoliter sample volumes in microfluidic systems. The hybrid microstructure
      consists of two hydraulically connected parts, a pulse micropump, and a
      multilevel cross-flow injector. Sample injection is accomplished by creating a
      transient pressure pulse in the sample line by means of the solenoid-based
      micropump. The sample line is aligned at right angles to the main carrier flow
      line. The two flow channels are located in two different parallel planes. The
      cross section of the two channels is defined by a self-sealing aperture in an
      elastomer. During the pressure pulse, the sample is introduced through this
      aperture directly into the main flow stream. Fast impulse-based injection causes
      rapid mixing of the injected sample with the main flow stream. This permits
      simple single-line manifold micro flow injection (MFI) systems. The
      deformation/relaxation of the elastomer is fast and repeatable; as such, rapid
      serial actuations essentially result in a larger injected sample volume without
      significantly affecting the peak shape. In the present form, 2-40-nL samples are
      easily injected by single injection, and the injected volume can be chosen by
      system parameters. The injection repeatability as observed by a photometric
      detector is better than 1.2% (n = 100).

PMID- 14572064
TI  - An energy-efficient self-regulating heater for flow-through applications.
AB  - In many experiments, a flow-through heating arrangement is needed to reduce
      reaction time. Often the reaction conditions require inertness of the wetted
      material. Heated reactors based on polymeric tubing, notably PTFE, are the most
      common, and such reactors are typically used in a manner in which they are put in
      a heated bath or an otherwise thermally conductive potting in which a heater and
      a temperature sensor are embedded for heating and temperature control. Polymeric
      tubes are poor conductors of heat; as such, most reactors of this type have very
      poor energy utilization. We describe here heated flow-through reactors where a
      wire runs through the entire length of the tubular reactor and where the wire is
      directly electrically heated. The wire may or may not be electrically insulated.
      If the exterior of the tube is well insulated, the energy efficiency of such a
      reactor in heating the fluid of interest is nearly unity. This makes it most
      suitable for battery-powered applications. If an appropriate wire with a
      significant temperature coefficient of resistance is chosen, monitoring the
      current through the device at constant applied voltage indicates the effective
      mean temperature of the device and thus allows effective temperature control
      without an additional sensor/controller with essentially instantaneous response.
      Temperature control within +/- 0.4 degrees C at a mean temperature of 65 degrees
      C and within +/- 0.9 degrees C at 87 degrees C have been achieved.

PMID- 14572065
TI  - Nanoinjector for capillary electrophoresis and capillary electrochromatography.
AB  - A rotary valve nanoinjector was devised for use in capillary electrophoresis (CE)
      and capillary electrochromatography (CEC). A fused-silica capillary tip was
      inserted in a small through-hole in the rotor. The narrow and short capillary
      tip, with an inner volume of 6-24 nL, was embedded in the hole using epoxy resin.
      The injection volume was confirmed chromatographically by comparing the peak
      areas obtained with the nanoinjector to those of a conventional injector. In
      addition, both the rotor and stator of the injector were made of a nonconducting
      material, polyimide resin, to be utilized for CE and CEC. The application of the
      nanoinjector for CE was demonstrated.

PMID- 14572066
TI  - Sheathless electrospray from polymer microchips.
AB  - In this study, sheathless electrospray from polymer microchips with conducting
      layer on the emitter tip is described for the first time. The electrospray
      emitter tips were fabricated directly from the end of the microchips that were
      made of polycarbonate or poly(methyl methacrylate) with injection molding. A
      variety of tip shapes and conducting coatings were evaluated using an
      electrospray time-of-flight mass spectrometer run in the sheathless mode. Stable
      electrospray was obtained both from hand-polished and machine-milled three
      dimensional tips coated with either polymer-embedded gold particles or graphite
      particles as the conducting layer. Sputtered gold, on the other hand, suffered
      from poor stability mainly due to bad adhesion to the polymer tip. The durability
      of the different coatings was confirmed with electrochemical experiments under
      simulated electrospray conditions. The relative standard deviations of the
      response received from the ion current of the MS analysis were in the range of
      3.5-12%. The detection limit for a standard mixture containing five neuropeptides
      was lower than 0.5 fmol. The low detection limit makes the emitter tips highly
      attractive for the analysis of low-abundance biological species.

PMID- 14572068
TI  - Comments on "Helical sorbent for fast sorption and desorption in solid-phase
      microextraction-gas chromatographic analysis".

PMID- 14572067
TI  - Amplified voltammetric detection of DNA hybridization via oxidation of ferrocene
      caps on gold nanoparticle/streptavidin conjugates.
AB  - Gold nanoparticle/streptavidin conjugates covered with 6-ferrocenylhexanethiol
      were attached onto a biotinylated DNA detection probe of a sandwich DNA complex.
      Due to the elasticity of the DNA strands, the ferrocene caps on gold
      nanoparticle/streptavidin conjugates are positioned in close proximity to the
      underlying electrode modified with a mixed DNA capture probe/hexanethiol self
      assembled monolayer and can undergo reversible electron-transfer reactions. A
      detection level, down to 2.0 pM (10 amol for the 5 microL of sample needed) for
      oligodeoxynucleotide samples was obtained. The amplification of the voltammetric
      signals was attributed to the attachment of a large number of redox (ferrocene)
      markers per DNA duplex formed. The ferrocene oxidation current increased with the
      target concentration and began to level off at a target concentration of 10 nM.
      An Excellent linearity was found within the range between 6.9 and 150.0 pM and
      reasonable relative standard deviations (between 3.0 and 13.0%) were obtained.
      The amenability of this method to the analyses of polynucleotides (i.e., PCR
      products of the pre-S gene of hepatitis B virus in serum samples) was also
      demonstrated. The method is shown to be simple, selective, reproducible, and cost
      effective and does not require labeling of the DNA targets.

PMID- 14572069
TI  - Results misinterpreted.

PMID- 14572070
TI  - GM products: at least a label.

PMID- 14572071
TI  - Staphylococcus not found in sludge, but controversy continues.

PMID- 14572073
TI  - Climate change undermines recovering lakes.

PMID- 14572072
TI  - Endocrine disrupter found in aircraft deicer.

PMID- 14572074
TI  - EPA perchlorate decision takes many by surprise.

PMID- 14572075
TI  - EPA strengthens some drinking water protections.

PMID- 14572076
TI  - Demonstrating carbon sequestration.

PMID- 14572078
TI  - Gauging the price of good health.

PMID- 14572077
TI  - Genomics tools in environmental impact assessment.

PMID- 14572079
TI  - Time trends of selected persistent organic pollutants in lake sediments from
      Greenland.
AB  - Sediments from seven lakes in West Greenland were used as natural archives to
      study past and present levels of PCBs (polychlorinated biphenyls, tri- to
      decachlorinated), tetra-BDE #47 (2,2',4,4'-bromodiphenyl ether), chlordane (cis-
      and trans-octachlordane) and HxCBz (hexachlorobenzene). The concentrations found
      are lower than or comparable to concentrations found in sediments from other
      Arctic regions and one to 2 orders of magnitude lower than concentrations
      typically found in sediments at lower latitudes. The observed temporal trends
      (direct and indirect dating) show a decreasing total PCB concentration. Even
      though local contamination sources exist, the POP deposition in the studied area
      is most likely a result from long-range transport. The hypothesis about "cold
      condensation" suggests a latitudinal fractionation to occur between different
      volatile compounds during the transport toward the pole. In this study a time
      delay in the deposition for the low-chlorinated PCBs (tri- and tetrachlorinated),
      compared to their emission histories and compared to higher chlorinated PCBs, was
      indicated. Although very low tetra-BDE #47 concentrations are observed in this
      study, there are indications for an increasing concentration in recent sediment
      layers that may reflect increasing environmental concentrations at lower
      latitudes. The investigated pesticides are still in use at lower latitudes,
      however neither chlordane nor HxCBz show any distinct temporal trend of
      increasing or decreasing concentration toward the sediment surface.

PMID- 14572080
TI  - Assessing forest fire as a potential PCDD/F source in Queensland, Australia.
AB  - Forest fires are suggested as a potential and significant source of
      polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs),
      even though no studies to date provide sufficient evidence to confirm forest
      fires as a source of PCDD/Fs. Recent investigations in Queensland, Australia have
      identified a widespread contamination of PCDDs (in particular OCDD) in soils and
      sediments in the coastal region from an unknown source of PCDD/Fs. Queensland is
      predominately rural; it has few known anthropogenic sources of PCDD/Fs, whereas
      forest fires are a frequent occurrence. This study was conducted to assess forest
      fires as a potential source of the unknown PCDD/F contamination in Queensland. A
      combustion experiment was designed to assess the overall mass of PCDD/Fs before
      and after a simulated forest fire. The results from this study did not identify
      an increase in sigmaPCDD/Fs or OCDD after the combustion process. However,
      specific non-2,3,7,8 substituted lower chlorinated PCDD/Fs were elevated after
      the combustion process, suggesting formation from a precursor. The results from
      this study indicate that forest fires are unlikely to be the source of the
      unknown PCDD contamination in Queensland, rather they are a key mechanism for the
      redistribution of PCDD/Fs from existing sources and precursors.

PMID- 14572081
TI  - Reconstructing tritium exposure using tree rings at Lawrence Berkeley National
      Laboratory, California.
AB  - Annual tritium exposures were reconstructed using tree cores from Pinus jeffreyi
      and Eucalyptus globulus near a tritiated water vapor release stack. Both tritium
      (3H) and carbon-14 (14C) from the wood were measured from milligram samples using
      accelerator mass spectrometry. Because the annual nature of the eucalyptus tree
      rings was in doubt, 14C measurements provided growth rates used to estimate the
      age for 3H determinations. A 30-yr comparison of organically bound tritium (OBT)
      levels to reported 3H release data is achieved using OBT measurements from three
      trees nearthe stack. The annual average 3H, determined from atmospheric water
      vapor monitoring stations, is comparable to the OBT in proximal trees. For
      situations without adequate historical monitoring data, this measurement-based
      historical assessment provides the only independent means of assessing exposure
      as compared to fate and transport models that require prior knowledge of
      environmental conditions and 3H discharge patterns.

PMID- 14572082
TI  - Variability of apparent particle density of an urban aerosol.
AB  - The day to day and diurnal variation of apparent particle density was studied
      using highly time-resolved measurements of particle number distribution and fine
      particle mass concentration. The study was conducted in Erfurt, Germany, from
      January 1, 1999, to November 22, 2000. A setup consisting of a differential
      mobility particle spectrometer and a laser aerosol spectrometer was used for
      particle number distribution measurements. PM2.5 particle mass was measured in
      parallel on an hourly basis using a tapered element oscillating microbalance
      (TEOM) and on daily base by using a Harvard marple impactor (HI). For the
      estimation of the mean apparent density of particles, number size distributions
      were converted into volume size distributions, assuming that the particles were
      spherically shaped. The volume size distributions were integrated over the range
      of 10 nm to 2.03 microm Stokes equivalent diameter to obtain volume
      concentrations. Mean apparent particle density was calculated as ratio of mass
      concentration and volume concentration. The mean apparent particle density,
      determined from HI and number size distribution on a daily basis was 1.6 +/- 0.5
      g cm(-3). We found a strong day-to-day variation of apparent density ranging from
      1.0 to 2.5 g cm(-3) (5th and 95th percentile). Furthermore, the apparent density
      showed pronounced diurnal pattern both in summer and in winter and also on
      weekdays and weekends. The apparent density was lowest in the morning and highest
      in the afternoon. The mean apparent density on an hourly basis was 1.4 +/- 0.5
      and 1.5 +/- 0.5 g cm(-3) for PM2.5TEOM and corrected PM2.5TEOM using regression
      equation between daily mass concentration of HI and TEOM, respectively. The
      strong diurnal variation of apparent particle density was associated
      predominantly with the vertical temperature inversion and with traffic intensity.
      Thus, the apparent particle density depends on the physical particle properties
      and might be related to chemical composition of the sampled particle.

PMID- 14572083
TI  - Emission and long-range transport of gaseous mercury from a large-scale Canadian
      boreal forest fire.
AB  - Field observations made at Harvard Forest [Petersham, MA, U.S.A. (42 degrees 54'
      N, 72 degrees 18' W)] during early July 2002 show clear evidence of long-range
      transport of gaseous mercury (Hg) in a smoke plume from a series of boreal forest
      fires in northern Quebec. These measurements indicated significant and highly
      correlated increases in Hg and CO during the plume event. The Hg:CO emissions
      ratio determined from the data (8.61 x 10(-8) mol mol(-1)) was combined with
      previously published information on CO emissions and biomass burned to determine
      a mean area-based Hg emission flux density for boreal forest fires (1.5 g Hg ha(
      1)), annual Hg emissions from Canadian forest fires (3.5 tonnes), and annual
      global Hg emissions from boreal forest fires (22.5 tonnes). Annual Hg emissions
      from boreal fires in Canada may equal 30% of annual Canadian anthropogenic
      emissions in an average fire year and could be as high as 100% during years of
      intense burning. The Hg:CO emissions ratio of this study was much lower than
      those reported for a temperate forest in Ontario and a pine/shrub vegetation in
      South Africa, suggesting that fire emission is dependent on biome/species and
      that any extrapolation from a single fire event to determine the global fire
      emission is speculative.

PMID- 14572084
TI  - Polybrominated diphenyl ethers in marine species from the Belgian North Sea and
      the Western Scheldt Estuary: levels, profiles, and distribution.
AB  - The Western Scheldt Estuary (SE) is subjected to a variety of suspected PBDE
      sources, such as a brominated flame retardant manufacturing plant, the Antwerp
      harbor, and the textile industry located further upstream the river. The Belgian
      North Sea (BNS) was included in this study to analyze the influence of the SE on
      the levels found in biota from the BNS locations. Benthic invertebrates, such as
      shrimp, crab, and starfish, benthic fish, such as goby, dab, plaice, and sole,
      and gadoid fish, such as bib and whiting, were sampled in the BNS (nonpolluted
      area) and the SE (polluted area) and analyzed to determine the concentrations and
      spatial variation of eight polybrominated diphenyl ethers (PBDEs 28, 47, 99, 100,
      153, 154, 183, and 209). Levels found in the SE samples were up to 30 times
      higher than those found in BNS samples, with a gradient increasing toward
      Antwerp. Levels in BNS ranged from 0.02 to 1.5 ng/g ww in benthic invertebrates
      and goby, from 0.06 to 0.94 ng/g ww in fish muscle, and from 0.84 to 128 ng/g ww
      in fish liver. For the SE samples, levels ranged from 0.20 to 29.9 ng/g ww in
      benthic invertebrates and goby, from 0.08 to 6.9 ng/g ww in fish muscle, and from
      15.0 to 984 ng/g ww in fish liver. BDE 209 could only be detected in eight liver
      samples from the SE and levels ranged between 3.4 and 37.2 ng/g ww. PBDE profiles
      of the various species at the different locations were compared. Differences in
      profile were attributed to different exposure and to differences in metabolism
      among species. Ratios between BDE 99 and 100 were found to be highly location and
      species dependent, which could be related to differences in metabolism. Some
      species, such as dab, plaice bib, and whiting, showed preferential accumulation
      of PBDEs in the liver. Higher brominated congeners in general showed higher
      affinity for liver than for muscle tissue.

PMID- 14572085
TI  - Atmospheric perfluorocarbons.
AB  - Collectively, man-made emissions of a few greenhouse gases may cause about the
      same amount of global warming as increasing carbon dioxide. Among the most potent
      of these non-CO2 greenhouse gases are the perfluorocarbons that have
      extraordinarily long atmospheric lifetimes of 10,000 to more than 50,000 yr. We
      report atmospheric concentrations over two decades, between 1978 and 1997, of the
      three most abundant perfluorocarbons--CF4, C2F6, and C3F8--and delineate the
      sources that account for the present abundances and trends. We show that C2F6 and
      C3F8 are present at only 2.9 and 0.2 pptv, respectively. CF4 is the most abundant
      perfluorocarbon at 74 pptv (in 1997) of which about 40 pptv are from natural
      emissions, 33 pptv from aluminum manufacturing, and 1 pptv from the semiconductor
      industry. The increasing trend of CF4 has slowed in recent years due to the major
      reductions in the emission rate per ton of aluminum produced. The effect of the
      falling emission factor is partially offset by increased production and
      increasing use by the semiconductor industry.

PMID- 14572086
TI  - Cooperative biosorption of copper on calcium alginate enclosing iminodiacetic
      type resin.
AB  - Composite gels of calcium alginate containing iminodiacetic type resin were
      prepared as a chemical analogue of biological tissues and membrane such as the
      cell wall. This chemical model was applied in copper biosorption from synthetic
      aqueous solutions. Experimental data on the composite were compared to those
      obtained for the biopolymer and the iminodiacetic-type resin separately and
      fitted into the ion exchange equilibrium model proposed in this work, which
      basically assumes that metal retention is the sum of the metal loaded onto the
      biopolymer and onto the resin. This model is tested with experimental data on
      copper biosorption on composite gels, including the equilibrium expressions of
      all the ionic species that are present in the system, the fraction of metal
      enclosed in the gel fluid, the gel volume variation, and the Donnan equilibrium
      theory. Another simplified model that only requires one equilibrium constant for
      each metal in the resin is shown to fit the results of the experiment fairly
      well, but it proves necessary to include an empirical parameter n into the
      equilibrium equation of copper in the resin to obtain the best fit of
      experimental data.

PMID- 14572087
TI  - Subspecies-level variation in the phytoextraction of weathered p,p'-DDE by
      Cucurbita pepo.
AB  - Previous studies indicate that Cucurbita pepo can phytoextract highly weathered
      persistent organic pollutants (POPs) from soil and translocate large quantities
      to aerial tissues. To investigate intraspecific variability in uptake potential,
      a field study was conducted to quantify the phytoextraction of weathered p,p'-DDE
      by 21 cultivar varieties of summer squash from two distinct subspecies, C. pepo
      ssp texana and C. pepo ssp pepo. Significant differences exist between the two
      subspecies, with average root and stem to soil bioconcentration factors (BCF, dry
      weight ratio of contaminant concentration in the vegetation to that in the soil)
      of 7.22 and 5.40 for ssp pepo and of 2.37 and 0.454 for spp texana, respectively.
      The amounts of weathered p,p-DDE extracted from the soil by ssp pepo and ssp
      texana were 0.301 and 0.065%, respectively, with maximum values within each
      subspecies of 0.780 and 0.182%, respectively. The quantities of 14 inorganic
      elements were determined in both the soil and tissues (roots, stems, leaves, and
      fruit) of all 21 cultivar varieties. Phosphorus concentrations in the tissues of
      ssp pepo were 14 (fruit)-73% (stems) greater than those of ssp texana. These data
      support our hypothesis that the unique ability of certain cultivars of C. pepo to
      phytoextract highly weathered POPs from soil is the result of low molecular
      weight organic acid exudation as a unique phosphorus acquisition mechanism.

PMID- 14572088
TI  - Simultaneous release of metals and sulfide in lacustrine sediment.
AB  - A single DGT (diffusive gradient in thin films) probe that could measure metals
      and sulfide simultaneously and at the same location was deployed in the surface
      sediment of a productive lake (Esthwaite Water). It contained a layer of AgI that
      binds sulfide overlying a layer of chelating resin that binds metals. Analysis
      for sulfide in two dimensions showed local sources of sulfide, 1-5 mm in
      diameter, at 8-11 cm depth within the sediment. A transect of trace metals
      measured at 100-microm intervals through the largest sulfide "hot spot"
      demonstrated concomitant release of Fe, Mn, Cu, Ni, and Co. Substantial
      supersaturation with respect to metal sulfides was observed for Fe and Co at the
      site of metal generation, but at a distance of less than 1 mm, solution
      concentrations were consistent with equilibration with amorphous FeS and CoS
      phases. Simple mass balance calculations were consistent with Fe being supplied
      from reductive dissolution of its oxides and with sulfide being supplied from
      reduction of sulfate. The observed concentrations of Cu, Ni, Co, and Mn could be
      accounted for by their release from iron oxides without invoking Mn reduction.
      The metals are removed rapidly (approximately 1 min) at the edge of the hot spot.
      These first observations of the simultaneous release of trace metals and sulfide
      are consistent with the known removal of metals by formation of their insoluble
      sulfides if the in situ kinetics of metal sulfide formation is on this time
      scale. The coproduction of reduced Fe and S suggests that iron- and sulfate
      reducing bacteria may exist together in the same localized zone of actively
      decomposing organic matter.

PMID- 14572089
TI  - Mechanisms of acute and chronic waterborne nickel toxicity in the freshwater
      cladoceran, Daphnia magna.
AB  - We present evidence that Mg2+ antagonism is one mechanism for acute toxicity of
      waterborne Ni to Daphnia magna. Acutely, adult D. magna were exposed to either
      control or 694 microg Ni L(-1) as NiSO4 in moderately soft water (45 mg L(-1) as
      CaCO3; background Ni approximately 1 microg Ni L(-1)) for 48 h without feeding.
      Chronically, adults were exposed to either control or 131 microg Ni L(-1) for 14
      days (fed exposure). These concentrations were approximately 65% and 12%,
      respectively, of the measured 48-h LC50 (1068 microg Ni L(-1)) for daphnid
      neonates in this water quality. The clearest effect of Ni exposure was on Mg2+
      homeostasis, as whole-body [Mg2+] was significantly decreased both acutely and
      chronically by 18%. Additionally, unidirectional Mg2+ uptake rate (measured with
      the stable isotope 26Mg) was significantly decreased both acutely and chronically
      by 49 and 47%, respectively, strongly suggesting that Ni is toxic to D. magna due
      at least in part to Mg2+ antagonism. No impact was observed on the whole-body
      concentrations or unidirectional uptake rates of Ca2+ during either acute or
      chronic Ni exposure, while only minor effects were seen on Na+ and Cl- balance.
      No acute toxic effect was seen on respiratory parameters, as both oxygen
      consumption rate (MO2) and whole-body hemoglobin concentration ([Hb]) were
      conserved. Chronically, however, Ni impaired respiratory function, as both MO2
      and [Hb] were significantly reduced by 31 and 68%, respectively. Acutely, Ni
      accumulation was substantial, rising to a plateau between 24 and 48 h of
      approximately 15 microg g(-1) wet weight--an increase of approximately 25-fold
      over control concentrations. Mechanisms of acute toxicity of Ni in D. magna
      differ from those in fish; it is likely that such mechanistic differences also
      exist for other metals.

PMID- 14572090
TI  - Effects of dietary methylmercury on reproductive endocrinology of fathead
      minnows.
AB  - Recent laboratory studies have demonstrated that environmentally realistic
      concentrations of dietary methylmercury can impair reproduction of fish. To
      evaluate relations between reproductive success and biomarkers of methylmercury
      exposure, we fed juvenile fathead minnows (Pimephales promelas) one of three
      diets contaminated with methylmercury: 0.06 (control), 0.87 (low), and 3.93
      (medium) microg of Hg g(-1) dry weight. At sexual maturity, fish were paired,
      allowed to reproduce, and then analyzed for total mercury, plasma testosterone
      (T), and 17beta-estradiol (E2). Diets did not affect survival or growth of
      fathead minnows. Methylmercury suppressed levels of T in males and E2 in females.
      Male fathead minnows fed the control diet had mean T concentrations 20% and 106%
      greater than those fed the low and medium diets; control females had mean E2
      concentrations 149% and 402% greater than those fed the low and medium diets.
      Methylmercury also inhibited gonadal development of females; the gonadosomatic
      index (GSI) of females fed the medium diet was 40% less than that of females fed
      control or low diets. Plasma levels of T in males and E2 in females were
      positively related to GSI. Methylmercury reduced the reproductive success of
      fathead minnows. Spawning success was 32% for pairs fed the control diet, 12% for
      pairs fed the low diet, and 0% for pairs fed the medium diet. Pairs fed the low
      diet required, on average, 5 d longer to spawn a clutch of eggs than the
      controls. Concentrations of methylmercury fed to fathead minnows in this study
      are also encountered by invertivorous and piscivorous fish in some methylmercury
      contaminated aquatic ecosystems. This suggests that reproduction of wild fishes
      may be adversely affected by methylmercury and that suppressed hormone levels may
      be used to indicate diminished reproduction of fish.

PMID- 14572091
TI  - Phenol and catechol biodegradation by the haloalkaliphile Halomonas campisalis:
      influence of pH and salinity.
AB  - Removal of aromatic compounds from alkaline and/or saline industrial wastewater
      is an environmental concern for industry. In addition, aromatics may be
      accumulating in soda lakes, unique natural systems, where the fate and toxicity
      of these contaminants is unknown. To determine the feasibility of aromatic
      compound biodegradation in saline and alkaline conditions, the effect of pH and
      salinity on the biodegradation of phenol as a model aromatic waste compound by
      the haloalkaliphilic bacterium Halomonas campisalis was examined. Phenol was
      degraded as a source of carbon and energy at pH 8-11 and 0-150 g/L NaCl.
      Metabolic intermediates catechol, cis,cis-muconate, and (+)-muconolactone were
      identified, thus indicating that phenol was degraded via the beta-ketoadipate
      metabolic pathway. Although phenol and catechol were completely degraded in all
      cases, small amounts of cis,cis-muconate accumulated proportionally to increases
      in pH. There was no noticeable influence of salinity on cis,cis-muconate
      accumulation except at 0 g/L NaCl where it was completely degraded. These results
      indicate that it may be feasible to use haloalkaliphiles forthe treatment of
      aromatics present in saline and/or alkaline systems. This is the first report of
      phenol and catechol biodegradation under combined saline and alkaline conditions.

PMID- 14572092
TI  - Role of dissolved organic matter composition on the photoreduction of Cr(VI) to
      Cr(III) in the presence of iron.
AB  - The photochemical reduction of Cr(VI) by iron and aquatic dissolved organic
      matter (DOM) was investigated. DOM sampled from a number of surface waters (a
      eutrophic wetland, a blackwater stream, and river water from a mix-use watershed)
      was used in this study. Moreover, a fulvic acid from Lake Fryxell, Antarctica,
      was also used to represent a DOM derived from a strictly autochthonous source.
      Cr(VI) reduction to Cr(III) at pH 5.5 was observed for all target DOMs used in
      this study, but rates varied widely. In general, photoreduction rates increased
      with increasing iron concentrations, but the type of DOM appeared to influence
      the kinetics to a larger degree. The rate of reduction was significantly greater
      for DOM derived from terrestrial systems than from predominantly autochthonous
      materials even if additional iron was added to the later. A positive correlation
      was observed between rates of Cr(VI) photoreduction and properties of the
      isolated DOM samples whereby faster reduction was observed for larger more
      aromatic substrates. On the basis of the fast rates reported for the dark
      reduction of Cr(VI) to Cr(III) by Fe(II)-organic ligands, we hypothesize that the
      rate-limiting step in these reactions is the photoreduction of Fe(III) to Fe(II)
      by a ligand-to-metal charge-transfer pathway after absorption of light by Fe(III)
      DOM complexes or by reduction of Fe(III) by superoxide or other intermediates
      formed after light absorption by DOM. Thus, the rate of Cr(VI) photoreduction to
      Cr(III) in natural sunlit waters is dependent upon both the amount of iron
      present and the nature of the dissolved organic matter substrate.

PMID- 14572093
TI  - Vinyl bromide as a surrogate for determining vinyl chloride reductive
      dechlorination potential.
AB  - Site evaluation for bioremediation of chlorinated ethenes may need treatability
      studies to assess the reductive dechlorination potential of vinyl chloride (VC).
      Dehalogenation of vinyl bromide (VB) was investigated as a surrogate measurement
      for the dechlorination potential of VC. VB dehalogenation rates and kinetics were
      studied and compared with those of VC by a methanogenic reductive dechlorinating
      enrichment culture that was dominated by Dehalococcoides species and by
      microcosms from two chloroethene-contaminated sites. The enrichment culture
      dehalogenated VB to ethene at higher rates than VC at similar concentrations. VB
      was dehalogenated with a higher enzyme affinity than was VC, as indicated by
      their half-velocity constants, 240 +/- 150 and 21 +/- 8 microM, for VC and VB,
      respectively. Cross-inhibition study exhibited some evidence for competitive
      inhibition between VC and VB, suggesting that their degradation might be
      catalyzed by the same enzyme in the culture. Laboratory microcosm studies using
      subsurface soil and groundwater from two contaminated sites demonstrated that the
      production of the reductive dehalogenation product (ethene) could be detected
      faster with VB as a substrate than with VC. As a result, a substantially shorter
      (up to 5-10 times) incubation time would be required to detect the same level of
      reductive dehalogenation activity using VB as a surrogate for VC in treatability
      assessments.

PMID- 14572094
TI  - Magnetic response of soils and vegetation to heavy metal pollution--a case study.
AB  - Fast and cost-effective detection of industrial pollution can significantly
      promote its ecological, economic, and social assessment. A magnetometric method,
      used for qualitative determination of anthropogenic contamination, meets these
      requirements but needs further development in more quantitative terms. It could
      be used successfully in numerous cases when the heavy metals coexist with
      strongly magnetic iron oxide particles in the source dust. We present an
      integrated magnetic and geochemical study that examines the utility of
      magnetometric techniques for rapid, qualitative detection of metallic pollutants
      in soils and vegetation. The new aspect of our approach, in comparison with
      previously published articles on this subject, is the combined investigation
      (magnetic and geochemical) of both soils and vegetation, thus using an additional
      medium for employing the magnetometry as a pollution proxy at a site. The study
      area is a small (approximately 3 km2) region in the suburbs of Sofia (Bulgaria),
      with the main pollution source being a metallurgical factory. Soil samples have
      been taken from the topmost 20 cm from private gardens, located at different
      distances from the factory. Vegetation samples were taken from ryegrass (both
      leaves and roots) and leaves from two kinds of deciduous trees (maple and
      acacia). The results show that both vegetation and soils are characterized by
      enhanced magnetic properties, compared to background material, which is due to
      the presence of magnetite particles of anthropogenic origin accompanying heavy
      metal emissions. SEM images and microprobe analyses reveal the presence of a
      significant amount of particles, containing heavy metals (including iron) in
      vegetation samples taken close to the main pollution source. Correlation analyses
      show a statistically significant link (correlation coefficients ranging from 0.6
      to 0.7) between magnetic susceptibility and the main heavy metals (Cu, Zn, Pb) in
      soil samples, indicating that the magnetic susceptibility can provide a proxy
      method for identifying the relative contribution of industrial pollution in soils
      and vegetation, that is reliable, inexpensive, and less time-consuming than
      standard chemical analyses.

PMID- 14572095
TI  - Membrane introduction mass spectrometry of nonpolar hydrocarbons using nitric
      oxide chemical ionization.
AB  - Selectivity enhancement of membrane introduction mass spectrometry of nonpolar
      alkanes, alkenes, and aromatic hydrocarbons in air samples by application of
      nitric oxide chemical ionization (NOCI/MIMS) is demonstrated. Membrane methods
      are useful for separating compounds (usually nonpolar organics) from air and
      water samples without costly and time-consuming sample preparation, and coupled
      with mass spectrometry, they provide good sensitivity. But they often suffer from
      lack of specificity in mixture analysis, particularly for saturated organics.
      Nitric oxide chemical ionization is able to produce strong unique ion signals for
      many hydrocarbon test compounds that can be used to identify and quantify the
      parent neutrals. Our observed detection limits for a number of test compounds
      were relatively high; however, the method could potentially be useful for
      environmental analytical applications (e.g., plume tracking) if the monitored
      compound was at elevated levels or if NOCI/MIMS is coupled with a trapping
      method.

PMID- 14572096
TI  - Partitioning of crude oil polycyclic aromatic hydrocarbons in aquatic systems.
AB  - This paper investigates the hypothesis that observed polycyclic aromatic
      hydrocarbon (PAH) concentrations in an aqueous system are equal to the sum of the
      organic phase and soluble phase molar concentrations. While the organic phase
      concentrations are proportional to the PAH mole fraction in the oil, the soluble
      phase molar concentrations are estimated using Raoult's law. A batch laboratory
      mixing vessel with a scalable mixing energy was loaded initially at various oil
      layer thicknesses (0.4-3.2 mm) which correspond to oil surface loadings (40-310
      mg/cm2). The vessel was agitated at constant mean shear rates (Gm = 5, 20 s(-1)).
      Total petroleum hydrocarbon (TPH) samples were taken periodically to estimate the
      entrainment rate as a function of initial oil layer thickness. TPH concentrations
      were measured in-situ using a laser scattering instrument (LISST-100) and ex-situ
      using gravimetric analysis. At a steady-state TPH concentration (>72 h),
      additional samples were analyzed for PAH concentration using GC/MS analysis. TPH
      concentrations increased over time according to a first-order kinetic model.
      Generally, the first-order rate constant and steady-state concentration both
      increased with increased oil loading and with increased Gm. In addition, measured
      PAH concentrations correlated well (r2 > 0.96) with those predicted by a
      partitioning model. These results are useful for assessing the effects of mixing
      and oil loading conditions on crude oil entrainment and PAH partitioning.

PMID- 14572097
TI  - Rejection efficiency of water quality parameters by reverse osmosis and
      nanofiltration membranes.
AB  - The objective of this study was to evaluate the effectiveness of reserve osmosis
      (RO) and nanofiltration (NF) membranes, under various solution chemistries, on
      water quality. The effects of organic carbon, divalent and monovalent cations,
      bacteria, and permeate drag on the rejection efficiencies of three different
      membranes were investigated through a series of laboratory bench-scale
      experiments. Quantitative models were successfully developed to predict the
      rejection of turbidity, divalent and monovalent cations, ultraviolet absorbance
      at 253.7 nm (UV254), and dissolved organic carbon (DOC) by membrane filtration.
      It was found that mechanical sieving (measured as molecular weight cutoff, MWCO)
      and electrostatic interactions were the most significant parameters since they
      were found to be important in nearly all models developed. For negatively charged
      membranes, under high ionic strength solution environments that repress
      electrostatic interaction between charged compounds and membranes, passage of
      compounds was mainly a function of size exclusion (i.e. MWCO). Further, of the
      feedwater parameters tested, bacteria concentration was observed to be the most
      significant influence on UV254, divalent cation and monovalent cation rejections.
      The developed models revealed that interactions between feedwater composition and
      membrane properties impacted the rejection efficiency of membranes as
      significantly as water composition and membrane properties individually.

PMID- 14572098
TI  - Occurrence and removal of estrogenic short-chain ethoxy nonylphenolic compounds
      and their halogenated derivatives during drinking water production.
AB  - The elimination of nonylphenol (NP), nonylphenol mono- and diethoxylates (NP1EO
      and NP2EO), nonylphenol carboxylates (NP1EC and NP2EC) and their brominated and
      chlorinated derivatives during drinking water treatment process in Sant Joan
      Despf waterworks in Barcelona was investigated utilizing a recently developed,
      highly sensitive LC-MS-MS method. The concentration of these potentially
      estrogenic compounds in raw water entering waterworks (taken from the Llobregat
      River, NE Spain) ranged from 8.3 to 22 microg/L, with NP2EC being the most
      abundant compound. Prechlorination reduced the concentration of short-chain
      ethoxy NPECs and NPEOs by about 25-35% and of NP by almost 90%. However, this
      reduction of concentrations was partially due to their transformation to
      halogenated derivatives. After prechlorination, halogenated nonylphenolic
      compounds represented approximately 13% of the total metabolite pool, of which
      97% were in the form of brominated acidic metabolites. The efficiency of further
      treatment steps to eliminate nonylphenolic compounds (calculated for the sum of
      all short-chain ethoxy metabolites including halogenated derivatives) was as
      follows: settling and flocculation followed by rapid sand filtration (7%),
      ozonation (87%), GAC filtration (73%), and final disinfection with chlorine
      (43%), resulting in overall elimination ranging from 96 to 99% (mean 98% for four
      sampling dates). A few of the nonylphenolic compounds (NP, NP1EC, and NP2EC) were
      also identified in drinking water; however, the residues detected were generally
      below 100 ng/L, with one exception for NP2EC in November 2001 when a
      concentration of 215 ng/L was detected.

PMID- 14572099
TI  - Removal of hexavalent chromium from wastewater using a new composite chitosan
      biosorbent.
AB  - A new composite chitosan biosorbent was prepared by coating chitosan, a
      glucosamine biopolymer, onto ceramic alumina. The composite bioadsorbent was
      characterized by high-temperature pyrolysis, porosimetry, scanning electron
      microscopy, and X-ray photoelectron spectroscopy. Batch isothermal equilibrium
      and continuous column adsorption experiments were conducted at 25 degrees C to
      evaluate the biosorbent for the removal of hexavalent chromium from synthetic as
      well as field samples obtained from chrome plating facilities. The effect of pH,
      sulfate, and chloride ion on adsorption was also investigated. The biosorbent
      loaded with Cr(VI) was regenerated using 0.1 M sodium hydroxide solution. A
      comparison of the results of the present investigation with those reported in the
      literature showed that chitosan coated on alumina exhibits greater adsorption
      capacity for chromium(VI). Further, experimental equilibrium data were fitted to
      Langmuir and Freundlich adsorption isotherms, and values of the parameters of the
      isotherms are reported. The ultimate capacity obtained from the Langmuir model is
      153.85 mg/g chitosan.

PMID- 14572100
TI  - A temperature responsive biopolymer for mercury remediation.
AB  - Tunable biopolymers based on elastin-like polypeptides (ELP) were engineered for
      the selective removal of mercury. ELP undergoes a reversible thermal
      precipitation within a wide range of temperatures and was exploited to enable
      easy recovery of the sequestered mercury. A bacterial metalloregulatory protein,
      MerR, which binds mercury with an unusually high affinity and selectivity, was
      fused to the ELP to provide the highly selective nature of the biopolymers.
      Selective binding of mercury was demonstrated at an expected ratio of 0.5
      mercury/biopolymer, and minimal binding of competing heavy metals (cadmium,
      nickel, and zinc), even at 100-fold excess, was observed. The sequestered mercury
      was extracted easily, enabling continuous reuse of the biopolymers. In repeating
      cycles, mercury concentration was reduced to ppb levels, satisfying even drinking
      water limits. Utility of the biopolymers with mercury-contaminated Lake Elsinore
      water was demonstrated with no decrease in efficiency. The nanoscale biopolymers
      reported here using metalloregulatory proteins represent a "green" technology for
      environmentally benign mercury removal. As nature offers a wide selection of
      specific metalloregulatory proteins, this technology offers promising solutions
      to remediation of other important pollutants such as arsenic or chromium.

PMID- 14572101
TI  - Characterization of gaseous and solid product from thermal plasma pyrolysis of
      waste rubber.
AB  - Pyrolysis of waste rubber in thermal plasma is studied for the purpose of
      producing gaseous fuel and recovering carbon black filler. The plasma reactor has
      a dc arc nitrogen plasma generator with a maximum electric power input of 62.5
      kVA and a reaction chamber of 50 mm inner diameter and 1000 mm height. The
      results of a series of experiments have shown that the main components of the
      gaseous product are H2, CO, C2H2, CH4, and C2H4; the heat value of the gas is
      about 5-9 MJ/Nm3. The solid product contains more than 80 wt % elemental carbon,
      has a surface area of about 65 m2/g, and is referred to as pyrolytic carbon black
      (CBp). X-ray photoelectron spectroscopy (XPS) analysis has revealed that the CBp
      has mainly graphitic carbon structure similar to those of commercial carbon
      black. The CBp may be used as semireinforcing carbon black in nontire rubber
      applications, or, after upgrading, as carbon black filler for tire. Thus thermal
      plasma pyrolysis is potentially a useful way of treating waste rubber for
      resource recovery.

PMID- 14572102
TI  - Selective coagulant recovery from water treatment plant residuals using Donnan
      membrane process.
AB  - Fouling of membrane surfaces by particulate matter and large organic molecules is
      relatively common for pressure-driven membrane processes, namely, reverse osmosis
      (RO), nanofiltration (NF), and ultrafiltration (UF). Donnan membrane process
      (DMP) or Donnan Dialysis is driven by electrochemical potential gradient across a
      semipermeable ion exchange membrane. Theoretically, DMP is not susceptible to
      fouling by fine particulates and/or large organic molecules. According to
      information available in the open literature, however, DMP has not been tried to
      treat slurry or sludge with relatively high concentration of suspended solids or
      large organic molecules. This study presents the salient results of an extensive
      investigation pertaining to selective alum recovery from water treatment
      residuals (WTR) using DMP. Water treatment plants use alum, Al2(SO4)3 x 14H2O, as
      a coagulant, alum being finally converted and discharged as insoluble aluminum
      hydroxide along with natural organic matters (NOM), suspended solids, and other
      trace impurities. One commercial cation exchange membrane, namely Nafion 117 from
      DuPont Chemical Co., was used in the study for treating WTR obtained from two
      different water treatment plants in Pennsylvania. A series of laboratory tests
      confirmed that over 70% of alum is easily recoverable, and recovered alum is
      essentially free of particulate matter, NOM, and other trace metals. Most
      importantly, after repeated usage in the presence of high concentration of NOM
      and suspended solids, there was no noticeable decline in aluminum flux through
      the membrane, i.e., membrane surface fouling was practically absent. The DMP
      process involves coupled transport of Al3+ and H+ across the cation exchange
      membrane, and intramembrane transport was the rate-limiting step. Experimentally
      determined aluminum-hydrogen interdiffusion coefficient (D(Al-H)) values within
      the membrane were quite high (approximately 10(-6) cm2/s) under representative
      conditions, thus confirming high alum recovery rate. DMP was also found equally
      effective in recovering Fe(III) based coagulants from WTR.

PMID- 14572103
TI  - A novel system for reducing leaching from formulations of anionic herbicides:
      clay-liposomes.
AB  - A new approach was developed for reducing leaching of herbicides and
      contamination of groundwater. Liposome-clay formulations of the anionic
      herbicides sulfometuron and sulfosulfuron were designed for slow release by
      incorporating the herbicide in positively charged vesicles of
      didodecyldimethylammonium (DDAB), which were adsorbed on the negatively charged
      clay, montmorillonite. Freeze fracture electron microscopy demonstrated the
      existence of DDAB vesicles and aggregated structures on external clay surfaces. X
      ray diffraction results for DDAB with montmorillonite imply the existence of DDAB
      bilayers with an oblique orientation to the basal plane within the clay
      interlayer space at adsorbed amounts beyond the cation exchange capacity of the
      clay. Adding DDAB with sulfometuron or sulfosulfuron to montmorillonite yielded
      95% or 83% adsorption of the herbicide at optimal ratios. Liposome-clay
      formulations exhibited slow release of the herbicides in water. Analytical
      measurements in soil columns demonstrated 2-10-fold reduction in leaching of the
      herbicides from liposome-clay formulations in comparison with commercial
      formulations. Percents of root growth inhibition of a test plant in the upper
      soil depths were severalfold higher for the liposome-clay formulations than for
      the commercial ones. Consequently, liposome-clay formulations of anionic
      herbicides can solve environmental and economical problems by reducing their
      leaching.

PMID- 14572104
TI  - Application of waves for remediation of contaminated aquifers.
AB  - A theory developed suggested that significant displacement of solute in saturated
      porous media results from the propagation of compression waves. Four independent
      one-dimensional experimental setups and a variety of laboratory methods were used
      to confirm the predictions of the theory, specifically aimed at developing a
      novel method of inducing compression waves for use in remediation of contaminated
      aquifers. Compaction and shock waves were emitted through granular porous media
      saturated with saline water. The changes in solute concentration at observation
      points along the propagating wave were used to verify the validity of theory. The
      first setup was designed mainly to provide a qualitative assessment (i.e.,
      changes in pressure due to the propagating wave were not recorded). In situ
      quantitative measurements of the pressure and electrical conductivity profiles
      along a sand column were done with the second and third experimental setups,
      respectively, to short and long shock waves. In the fourth setup, solute
      displacement was visualized by X-ray absorption. The findings were consistent
      with the theory in all experimental setups.

PMID- 14572105
TI  - In-situ control of DNAPL density using polyaphrons.
AB  - Once spilled into soils, dense nonaqueous phase liquids (DNAPLs) such as
      chlorinated solvents migrate deep into the subsurface because of their high
      density. Their downward migration typically continues until capillary forces
      balance gravitational forces or until essentially impermeable strata are reached.
      Efforts to mobilize the DNAPL for remediation purposes risks driving the
      contaminants deeper, which has spurred research for modifying buoyancy forces in
      situ. In this paper, a novel means of controlling the density of a DNAPL phase
      using polyaphrons is presented. Polyaphrons are a class of high internal phase
      ratio emulsions (HIPREs) that have unusual properties such as indefinite
      stability and flow properties through porous media. They provide a means of
      selectively delivering a light organic phase liquid to the vicinity of the DNAPL
      phase. Upon destabilization of the polyaphron by a polyvalent cation, the light
      internal phase mixes with the DNAPL to produce a nonaqueous phase of lower
      density than the original contaminant. The negative buoyancy of the DNAPL can
      thus be reversed. This approach holds great promise for manipulating DNAPL
      densities prior to or during remediation treatments.

PMID- 14572106
TI  - Photocatalytic degradation of polystyrene plastic under fluorescent light.
AB  - Plastic is used widely all over the world, due to the fact that it is low cost,
      is easily processable, and has lightweight properties. However, the hazard of
      discarding waste plastic, so-called "white pollution", is becoming more and more
      severe. In this paper, solid-phase photocatalytic degradation of polystyrene (PS)
      plastic, one of the most common commercial plastics, over copper phthalocyanine
      (CuPc) sensitized TiO2 photocatalyst (TiO2/CuPc) has been investigated under
      fluorescent light irradiation in the air. UV-vis spectra show that TiO2/CuPc
      extends its photoresponse range to visible light, contrasting to only UV light
      absorption of pure TiO2. The PS photodegradation experiments exhibit that higher
      PS weight loss rate, lower PS average molecular weight, less amount of volatile
      organic compounds, and more CO2 can be obtained in the system of PS-(TiO2/CuPc),
      in comparison with the PS-TiO2 system. Therefore, PS photodegradation over TiO2
      CuPc composite is more complete and efficient than over pure TiO2, suggesting the
      potential application of dye-sensitized TiO2 catalyst in the thorough
      photodegradation of PS plastic under fluorescent light. During the
      photodegradation of PS plastic, the reactive oxygen species generated on TiO2 or
      TiO2/CuPc particle surfaces play important roles in chain scission. The present
      study demonstrates that the combination of polymer plastic with dye-sensitized
      TiO2 catalyst in the form of thin film is a practical and useful way to
      photodegrade plastic contaminants in the sunlight.

PMID- 14572107
TI  - Removal of arsenic from synthetic acid mine drainage by electrochemical pH
      adjustment and coprecipitation with iron hydroxide.
AB  - Acid mine drainage (AMD), which is caused by the biological oxidation of sulfidic
      materials, frequently contains arsenic in the form of arsenite, As(III), and/or
      arsenate, As(V), along with much higher concentrations of dissolved iron. The
      present work is directed toward the removal of arsenic from synthetic AMD by
      raising the pH of the solution by electrochemical reduction of H+ to elemental
      hydrogen and coprecipitation of arsenic with iron(III) hydroxide, following
      aeration of the catholyte. Electrolysis was carried out at constant current using
      two-compartment cells separated with a cation exchange membrane. Four different
      AMD model systems were studied: Fe(III)/As(V), Fe(III)/As(III), Fe(II)/As(V), and
      Fe(II)/As(III) with the initial concentrations for Fe(III) 260 mg/L, Fe(II) 300
      mg/L, As(V), and As(III) 8 mg/L. Essentially quantitative removal of arsenic and
      iron was achieved in all four systems, and the results were independent of
      whether the pH was adjusted electrochemically or by the addition of NaOH. Current
      efficiencies were approximately 85% when the pH of the effluent was 4-7. Residual
      concentrations of arsenic were close to the drinking water standard proposed by
      the World Health Organization (10 microg/L), far below the mine waste effluent
      standard (500 microg/L).

PMID- 14572108
TI  - Relative solubility of cations in Class F fly ash.
AB  - Coal utilization byproducts (CUB), such as fly ash, contain cations that may be
      released during exposure to fluids such as acid rain or acid mine drainage.
      Researchers at the Department of Energy's National Energy Technology Laboratory
      (DOE/NETL) have conducted a long-term column leaching study of 32 Class F fly ash
      samples from pulverized coal (PC) combustion, and quantified the release of 19
      cations in four leachants with a pH between 1.2 and 12. The relative solubility
      (M(L/T)) of each cation was defined as the total mass leached (M(L)) relative to
      the concentration (M(T)) of that element in the fly ash sample. A frequency
      distribution of relative solubility values was computed with ranges defined as
      insoluble, slightly soluble, moderately soluble, and very soluble. On the basis
      of this sample set, Ba, Cd, Fe, Pb, Sb, and Se in PC fly ash are insoluble. The
      elements Al, Be, Ca, Co, Cr, Cu, K, Mg, Mn, Na, Ni, and Zn are slightly to
      moderately acid soluble. Only Ca and Na are water soluble; As and Ca are soluble
      in the basic solution, The results of this study indicate that the extent to
      which cations in Class F PC fly ash can be leached by naturally occurring fluids
      is very limited.

PMID- 14572109
TI  - Formation and destruction of CH2O in the exhaust system of a gas engine.
AB  - A computational study of chemical reactions occurring in the exhaust system of
      natural gas engines has been conducted, emphasizing the formation and destruction
      of formaldehyde. The modeling was based on a detailed reaction mechanism,
      developed for describing oxidation of C1-C2 hydrocarbons and formaldehyde. The
      mechanism was validated against data from laboratory flow reactors and from the
      exhaust system of a full-scale gas engine. A parametric study of the exhaust
      system chemistry was performed, investigating the effect of temperature,
      stoichiometry, pressure, and exhaust gas composition. The results indicate a
      complex interaction between unburned hydrocarbons (UHC), formaldehyde, and
      nitrogen oxides. Above 850 K, partial oxidation of unburned hydrocarbons may
      occur, resulting in net formation or net destruction of CH2O depending on the
      unburned hydrocarbons/CH2O ratio and the reaction conditions. At the typical
      unburned hydrocarbons/CH2O ratio of 1.0-1.5% for gas engines, net formaldehyde
      formation may occur in the exhaust system if temperatures above 850 K are
      reached.

PMID- 14572110
TI  - Recycling of meat and bone meal animal feed by vacuum pyrolysis.
AB  - Due to the recent bovine spongiform encephalopathy (BSE) crisis in the European
      beef industry, the use of animal-derived products to feed cattle is now severely
      restricted. Large quantities of waste animal meat and bone meal (MBM), also known
      as animal flour, have to be safely disposed of or transformed. One disposal
      option is pyrolysis. Vacuum pyrolysis of an animal flour sample has been
      performed in a laboratory reactor. The results obtained revealed that vacuum
      pyrolysis can be an attractive alternative to incineration and cement kilns. The
      process generated a combustible gas (15.1 wt %), a high calorific value oil (35.1
      wt %), a solid residue rich in minerals (39.1 wt %), and an aqueous phase rich in
      organics (10.7 wt %). The gas and the aqueous phase can be used to provide heat
      to the vacuum pyrolysis reactor and the MBM drying unit. The oil can be used
      alone or mixed with petroleum products as a fuel in boilers or gas turbines.
      Conversion of animal waste by pyrolysis into fuels can contribute to the
      reduction of greenhouse gases. It is suggested to use the solid residue for
      agricultural soil enrichment in minerals and as a soil moisturizer.

PMID- 14572111
TI  - Comment on "Effect of methyl tert-butyl ether on the bioconcentration and
      photoinduced toxicity of fluoranthene in fathead minnow larvae (Pimephales
      promelas)".

PMID- 14572112
TI  - Arousal from sleep--perspectives relating to autonomic function.

PMID- 14572113
TI  - On the value of measuring CSF hypocretin-1 in diagnosing narcolepsy.

PMID- 14572114
TI  - Novel measures of daytime central nervous system function following sleep
      disruption.

PMID- 14572115
TI  - Sleep in postmenopausal women: better sleep for less satisfaction.

PMID- 14572116
TI  - Sleep and circadian rhythm disturbances in patients with delayed sleep phase
      syndrome.
AB  - STUDY OBJECTIVES: The objective of this study was to clarify sleep
      characteristics and pathophysiology in patients with delayed sleep phase syndrome
      (DSPS), which is a major circadian rhythm sleep disorder subtype. DESIGN:
      Polysomnography was performed for 2 consecutive nights and core body temperature
      was sampled for 7 consecutive days, including the polysomnography study period,
      in all subjects. Findings were compared and statistically analyzed between
      patients with DSPS and matched controls. SETTING: Sleep disorders unit in
      National Center Hospital. PARTICIPANTS: 11 DSPS patients and 11 age-matched
      healthy volunteers. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Sleep latency,
      total sleep time, wakefulness after sleep-onset, and the amount and percentage of
      Stage 1 sleep were greater in DSPS patients than in volunteers. Sleep efficiency
      and the amount and percentage of slow wave sleep were lower in DSPS patients than
      in volunteers. Compared with the healthy volunteers, DSPS patients showed a
      decreased number and different temporal distribution of high-voltage and low
      frequency delta waves. The time of minimum body temperature appeared earlier in
      the sleep phase for the patients than for the volunteers. Significant correlation
      was found between the amount of slow wave sleep and the time from sleep onset to
      minimum body temperature and between the amount and percentage of slow wave sleep
      and time from minimum body temperature to sleep offset. CONCLUSIONS: Disturbances
      were found in the sleep structure of patients with DSPS, and these disturbances
      were related to the discrepancy between patients and controls in the phase
      relationship difference between sleep and core body temperature rhythms.

PMID- 14572118
TI  - Objective and subjective sleep quality in premenopausal, perimenopausal, and
      postmenopausal women in the Wisconsin Sleep Cohort Study.
AB  - STUDY OBJECTIVE: Assess objectively measured sleep quality in premenopausal,
      perimenopausal, and postmenopausal women. DESIGN: Observational epidemiology
      study. SETTING: Community-based. PARTICIPANTS: Probability sample of 589
      premenopausal, perimenopausal, and postmenopausal women recruited from state
      employee records. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Menopausal
      status was determined by menstrual history, surgical history, and use of hormone
      replacement therapy. Sleep quality was objectively measured by full in-laboratory
      polysomnography and by self-reported sleep problems. Linear and logistic
      regression were used to estimate associations adjusted for potential confounding
      factors. OBJECTIVE: Sleep quality was not worse in perimenopausal or
      postmenopausal women, compared with premenopausal women. To the contrary,
      postmenopausal woman had more deep sleep (16% vs 13% stages 3/4, P < 0.001) and
      significantly longer total sleep time (388 minutes vs 374 minutes, P = 0.05).
      Menopausal status was moderately related to self-reported dissatisfaction with
      sleep but was not consistently associated with symptoms of insomnia or
      sleepiness. CONCLUSIONS: Menopause is not associated with diminished sleep
      quality measured by polysomnography. Although perimenopausal and postmenopausal
      women, relative to premenopausal women, were less satisfied with their sleep,
      menopause was not a strong predictor of specific sleep-disorder symptoms.
      Symptoms and signs of sleep abnormalities in midlife women should not be
      attributed primarily to menopause before ruling out underlying sleep disorders.

PMID- 14572117
TI  - Month of birth as a risk factor for narcolepsy.
AB  - STUDY OBJECTIVES: A loss of hypocretin neurons has been observed in human
      narcolepsy; however, the cause of this disorder is still unknown. While family
      history and genetic factors are important individual risk factors for narcolepsy,
      environmental factors also contribute to the pathogenesis of the disease. The aim
      of the study was to find out whether there is a seasonality of month of birth in
      narcoleptic patients. DESIGN: Diagnosis of narcolepsy with cataplexy was based on
      International Classification of Sleep Disorders criteria with clinical, standard
      polysomnographic, and Multiple Sleep Latency Test features. PATIENTS AND SETTING:
      The birth dates of 886 patients with a clear-cut diagnosis of narcolepsy with
      cataplexy from 3 large narcolepsy databases (352 from Montpellier-France, 157
      from Montreal-Canada, and 377 from Stanford-United States of America) were
      compared with those of 35,160,522 subjects from the general population.
      MEASUREMENTS AND RESULTS: Patients with narcolepsy had a significantly different
      seasonality of month of birth compared to that of the general population. The
      monthly distribution of birth yielded a peak in March with a maximal odds ratio
      at 1.45 and a trough in September with a minimal odds ratio at 0.63. No gender or
      country of origin differences were observed. CONCLUSIONS: A birth seasonality in
      the development of narcolepsy suggests the presence of environmental factors
      acting in combination with genetic factors during the fetal or perinatal period,
      in terms of an autoimmune process targeting the hypocretin system.

PMID- 14572119
TI  - The prevalence of restless legs syndrome among pregnant women in Japan and the
      relationship between restless legs syndrome and sleep problems.
AB  - STUDY OBJECTIVES: To clarify the prevalence of restless legs syndrome (RLS) in
      pregnant women living in Japan and to analyze the relationship between sleep
      problems and RLS, in order to discuss ways for pregnant women to obtain
      comfortable sleep and to improve the health of both the mother and child. DESIGN:
      A cross-sectional questionnaire survey. SETTING: 500 clinical institutions with
      maternity services were randomly sampled from a list of organizations identified
      in a survey by the Japan Association of Obstetricians and Gynecologists. Of these
      500 institutions, 260 participated in the survey. PARTICIPANTS: 16,528 pregnant
      women living in Japan. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: In this
      survey of pregnant women, the prevalence of RLS was found to be 19.9%. An
      analysis was conducted on the relationship between RLS and other factors such as
      subjective evaluation of sleep, difficulty initiating sleep, difficulty
      maintaining sleep, early morning awaking, and excessive daytime sleepiness. The
      result of this analysis suggested that women with these sleep-related problems
      were more likely to have RLS than those without. In addition, RLS was more
      prevalent in the later stages of pregnancy. CONCLUSION: In the pregnant women in
      our survey, the prevalence of RLS was found to be 19.9%, which is higher than the
      prevalence of RLS that has been found in the general public in a previous study.
      This suggests that RLS-related sleep problems may be an important public health
      issue among pregnant women in Japan. This finding may have implications for
      attempts to improve sleep hygiene in this group.

PMID- 14572120
TI  - Predictors of objective sleep tendency in the general population.
AB  - STUDY OBJECTIVES: Daytime sleepiness is a pervasive problem that is associated
      with a significant public-health burden. Although self-reported measures of
      daytime sleepiness may be useful in identifying at-risk individuals, there is
      significant controversy because there are no population-based data relating
      subjective and objective measures of daytime sleep tendency. The aims of this
      study were to examine the associations between the Multiple Sleep Latency Test
      (MSLT), an objective measure of daytime sleep tendency, and self-reported
      information on the Epworth Sleepiness Scale (ESS) and nighttime sleep duration in
      the general population. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS:
      Population-based sample of 261 women and 371 men, mean age of 50.8 years,
      enrolled in the Wisconsin Sleep Cohort Study. MEASUREMENTS: MSLT, ESS, and self
      reported sleep duration prior to the MSLT. RESULTS: Using survival analysis to
      model the time to sleep onset during the MSLT, we found that individuals with an
      intermediate (6-11) and high (> or = 12) ESS score had a 30% and 69% increase in
      risk for sleep onset during the MSLT, respectively, compared to individuals with
      a low ESS score (< or = 5). A dose-response relationship between self-reported
      duration of nighttime sleep and objective sleep tendency was also observed.
      Compared to individuals reporting more than 7.50 hours of sleep (highest
      tertile), individuals reporting 6.75 to 7.50 hours and less than 6.75 hours
      (lowest tertile) had a 27% and 73% increase in risk for sleep onset during the
      MSLT, respectively. CONCLUSIONS: Subjective reports of daytime sleep tendency on
      the ESS and the duration of nighttime sleep are associated with the results of
      the MSLT in the general population.

PMID- 14572121
TI  - Waking quantitative electroencephalogram and auditory event-related potentials
      following experimentally induced sleep fragmentation.
AB  - STUDY OBJECTIVES: Experimental sleep fragmentation involves inducing arousals by
      administering intrusive auditory stimuli throughout the night. It is intended to
      model the frequent and periodic disruption experienced in common sleep disorders.
      Sleep fragmentation leads to daytime sleepiness, although evidence of performance
      impairment has been inconsistent. The purpose of this study was to investigate
      brain physiology associated with this level of sleep disruption. Specifically,
      quantitative analysis of electroencephalography was carried out, and auditory
      event-related potentials were recorded during daytime performance assessment
      following sleep fragmentation in good sleepers. DESIGN: Participants spent 4
      consecutive 24-hour periods in the laboratory. On nights 2 and 3, sleep was
      fragmented using auditory stimuli that were delivered with increasing intensity
      until an arousal was noted. This design aimed to investigate the cumulative
      effects of sleep fragmentation on daytime functioning. SETTING: Data were
      collected in a sleep research laboratory during a 96-hour protocol. PARTICIPANTS:
      Eight healthy adults (mean age = 33.25) with no sleep complaints. MEASUREMENTS
      AND RESULTS: During the day, participants performed a 40-minute computerized test
      battery at 2-hour intervals (9:00 am -7:00 pm). The battery was presented in a
      fixed order and included measures of mood, sleepiness, reaction time, and serial
      addition or subtraction. Results indicated that subjective sleepiness and mood
      were impaired following sleep-fragmentation nights, compared to both baseline and
      recovery conditions. No performance deficits were apparent. The alpha:theta
      ratio, reflecting relative slowing of the electroencephalogram, was dramatically
      reduced following the second night of sleep fragmentation. Reductions in N1
      amplitude of the event-related potentials indicated that attention was impaired
      with respect to early encoding processes following sleep fragmentation.
      CONCLUSIONS: Electroencephalographic and event-related potentials data illustrate
      impairment in information-processing capabilities associated with reduced arousal
      elicited by experimental sleep fragmentation. This subtle degree of sleep
      disruption, where total sleep time is not reduced, leads to sustained impairment
      in alertness and attention.

PMID- 14572122
TI  - Daytime exposure to bright light, as compared to dim light, decreases sleepiness
      and improves psychomotor vigilance performance.
AB  - STUDY OBJECTIVES: This study examined the effects of bright light exposure, as
      compared to dim light, on daytime subjective sleepiness, incidences of slow eye
      movements (SEMs), and psychomotor vigilance task (PVT) performance following 2
      nights of sleep restriction. DESIGN: The study had a mixed factorial design with
      2 independent variables: light condition (bright light, 1,000 lux; dim light, < 5
      lux) and time of day. The dependent variables were subjective sleepiness, PVT
      performance, incidences of SEMs, and salivary melatonin levels. SETTING: Sleep
      research laboratory at Monash University. PARTICIPANTS: Sixteen healthy adults
      (10 women and 6 men) aged 18 to 35 years (mean age 25 years, 3 months).
      INTERVENTIONS: Following 2 nights of sleep restriction (5 hours each night),
      participants were exposed to modified constant routine conditions. Eight
      participants were exposed to bright light from noon until 5:00 pm. Outside the
      bright light exposure period (9:00 am to noon, 5:00 pm to 9:00 pm) light levels
      were maintained at less than 5 lux. A second group of 8 participants served as
      controls for the bright light exposure and were exposed to dim light throughout
      the entire protocol. MEASUREMENTS AND RESULTS: Bright light exposure reduced
      subjective sleepiness, decreased SEMs, and improved PVT performance compared to
      dim light. Bright lights had no effect on salivary melatonin. A significant
      positive correlation between PVT reaction times and subjective sleepiness was
      observed for both groups. Changes in SEMs did not correlate significantly with
      either subjective sleepiness or PVT performance. CONCLUSIONS: Daytime bright
      light exposure can reduce the impact of sleep loss on sleepiness levels and
      performance, as compared to dim light. These effects appear to be mediated by
      mechanisms that are separate from melatonin suppression. The results may assist
      in the development of treatments for daytime sleepiness.

PMID- 14572123
TI  - Predictors of longitudinal change in sleep-disordered breathing in a nonclinic
      population.
AB  - STUDY OBJECTIVES: To quantify and identify the determinants of the 5-year change
      in the respiratory disturbance index (RDI). DESIGN: Longitudinal cohort study
      (Cleveland Family Study). Multivariate analyses were used to quantify baseline
      RDI and RDI change. SETTING: Community-based study. PARTICIPANTS: 486 cohort
      members (62% from families of probands with sleep-disordered breathing [SDB])-
      mean age 31.6 +/- 17.9 (SD) years, 60% female, 21% Black ethnicity--who underwent
      2 assessments over 5.3 +/- 0.9 (SD) years. INTERVENTIONS: NA. MEASUREMENTS: The
      RDI was measured twice over approximately 5 years with in-home monitoring.
      Symptoms and medical histories were obtained from standardized questionnaires,
      and weight, height, and blood pressure were measured. RESULTS: The prevalence of
      SDB (defined by a RDI > or = 15), increased from 13.7% to 23.4% (P < 0.01) in men
      and from 8.3% to 11.4% (P = 0.13) in females. Baseline and follow-up mean RDIs
      were 6.0 +/- 10.0 and 8.6 +/- 14.3; both were higher in older individuals, in
      men, and in those with a higher body mass index. Median 5-year change in RDI
      varied nonlinearly with age (-0.1, 1.1, 2.3, and 0.9, for those < 18, 19-40, 41
      54, and > or = 55 years, respectively) and obesity (2.8 vs -0.1, for the top
      versus lowest body mass index quartile). The effects of changing weight and aging
      varied in population subgroups. At any given age and weight, the RDI increased
      less in women. CONCLUSIONS: Longitudinal change in the RDI varies nonuniformly
      with age, sex, and weight. Older heavier men may experience the highest rate of
      increase in RDI over time and, thus, may benefit most from prospective
      monitoring.

PMID- 14572124
TI  - Measurement of changes in cytochrome oxidase redox state during obstructive sleep
      apnea using near-infrared spectroscopy.
AB  - STUDY OBJECTIVES: To use near-infrared spectroscopy to investigate the effect of
      obstructive sleep apnea on cytochrome oxidase, the terminal enzyme of the
      mitochondrial respiratory chain. DESIGN: Observational study. SETTING: Teaching
      hospital sleep unit. PATIENTS: Subjects with diagnosed moderate to severe
      obstructive sleep apnea were recruited from the sleep clinic. INTERVENTIONS:
      Subjects were invited to attend 2 daytime sleep-study sessions, which included
      near-infrared monitoring of cerebral oxygenation and cytochrome-oxidase oxidation
      state. In addition, in study session 1, full polysomnography was performed (8
      subjects, 303 apneas), and in study session 2, arterial oxygen saturation,
      cerebral blood flow velocity, and blood pressure were monitored (7 subjects, 287
      apneas). MEASUREMENTS AND RESULTS: In study session 1, mean (+/- SD) cytochrome
      oxidase changes ranged from 0.48 +/- 0.08 microM to 0.13 +/- 0.05 microM. The
      magnitude of cytochrome-oxidase change correlated significantly with the
      magnitude of change in the cerebral tissue oxygenation index (P < .001). In study
      session 2, there were significant correlations between arterial oxygen-saturation
      changes and cytochrome-oxidase redox changes and between Doppler cerebral blood
      flow velocity changes and cytochrome-oxidase redox changes (P < .001 and P =
      .001, respectively). CONCLUSIONS: Changes in directly measured cerebral tissue
      saturation and changes in arterial saturation and cerebral blood flow velocity
      (the 2 main factors affecting cerebral oxygenation) are associated with changes
      in cytochrome-oxidase oxidation state. The reduced cerebral oxygenation that
      occurs during obstructive sleep apnea is associated with changes in the
      intracellular redox state.

PMID- 14572125
TI  - Change in periodic limb movement index during treatment of obstructive sleep
      apnea with continuous positive airway pressure.
AB  - STUDY OBJECTIVES: The following hypotheses were investigated: 1) severe
      obstructive sleep apnea (OSA) can mask concurrent periodic limb movement (PLM)
      disorder (PLMD), which becomes evident or worsens after treatment with continuous
      positive airway pressure (CPAP); 2) in patients with mild OSA, PLMs are not
      masked but may be triggered by subclinical hypopneas or respiratory effort
      related arousals and improve after CPAP. DESIGN: Retrospective analysis was
      performed on 2 polysomnographic studies per patient--1 baseline, the second with
      CPAP titration. The apnea-hypopnea index (AHI) and PLM index (PLMI) under the 2
      conditions were statistically analyzed. SETTING: University hospital sleep
      disorders center. PATIENTS: Patients were selected if they had a baseline AHI of
      5 or greater and CPAP titration resulted in reduced AHI. Also, each needed to
      have either a PLMI of 5 or greater on baseline PSG or during CPAP titration.
      Patients who started or discontinued a medication that could affect PLMs after
      the baseline PSG were excluded. INTERVENTIONS: As clinically indicated, CPAP for
      OSA. MEASUREMENTS AND RESULTS: Eighty-six patients qualified and were divided
      into 3 groups based on OSA severity. Significant correlations (P < 0.05) were
      found between AHI and PLMI on the baseline PSG (-0.50), between AHI on baseline
      PSG and PLMI on CPAP titration (0.49), and between PLMI on baseline PSG and on
      CPAP titration (-0.21). The increase in PLMI during CPAP titration in patients
      with severe OSA was statistically significant (P < 0.001). The PLMI decreased
      with CPAP in 20 of 86 patients, mostly in the mild OSA subgroup. Regression of
      post-CPAP reduction of AHI and change in PLMI yielded a significant logarithmic
      relationship (R2 = 0.3042). CONCLUSIONS: Severity of OSA may determine the effect
      of CPAP on PLMs. The PLMs may increase in moderate to severe OSA due mainly to
      "unmasking" of underlying PLMD. The PLMs may decrease in mild OSA post-CPAP due
      to resolution of PLMs associated with respiratory effort-related arousals. This
      suggests that PLMs may have more than 1 etiology and may be categorized as
      spontaneous (as in PLMD) and induced (when secondary to respiratory effort
      related arousals).

PMID- 14572126
TI  - A randomized crossover efficacy trial of oral CPAP (Oracle) compared with nasal
      CPAP in the management of obstructive sleep apnea.
AB  - STUDY OBJECTIVES: To determine the therapeutic efficacy and viability of a novel
      oral interface for continuous positive airway pressure (CPAP) compared with
      conventional nasal interfaces. DESIGN: A randomized single-blind crossover study.
      SETTING: Hospital-based sleep laboratory. PATIENTS OR PARTICIPANTS: 21 CPAP-naive
      patients with obstructive sleep apnea (baseline apnea-hypopnea index, 85 +/- 36)
      INTERVENTIONS: Nasal CPAP and oral CPAP MEASUREMENTS AND RESULTS: Patients were
      each treated for two 4-week periods using nasal CPAP and oral CPAP. The CPAP
      titrations were undertaken at the start of each treatment arm. Outcome measures
      were recorded at baseline and at the end of each treatment arm. These included
      polysomnography variables, CPAP compliance, subjective sleepiness, obstructive
      sleep apnea symptom ratings, and adverse effects. There were no significant
      differences between oral and nasal interfaces for the on-CPAP frequency of apneas
      and hypopneas (mean difference, nasal-oral [95%CI] = -4.6[-10.1-1.0]/h; P = 0.06)
      or arousals (-3.0 [-7.8-1.8]/h; P = 0.23). There were also no statistically
      significant differences between interfaces for scores on the Epworth Sleepiness
      Scale (-0.7 [-3.1-1.7]; P = 0.20), obstructive sleep apnea symptoms (-7.7 [-17.7
      2.4]; P = 0.052), CPAP compliance (0.3 [-0.5-1.1] h/night; P = 0.50), CPAP
      pressure (0.05 [-0.66-0.76] cmH20; P = 0.73), CPAP side effects scores (-2.0 [
      5.3-1.4]; P = 0.23), or mask preference (P = 0.407). In addition, both nasal and
      oral interfaces significantly improved polysomnographic variables, Epworth
      Sleepiness Scale scores, obstructive sleep apnea symptoms, and CPAP compliance
      from baseline (all P < 0.05). CONCLUSIONS: This preliminary study indicates that
      oral CPAP has similar efficacy to traditionally applied nasal CPAP in treating
      obstructive sleep apnea. Additional large studies are required to determine the
      range of clinical situations where oral CPAP is indicated.

PMID- 14572127
TI  - Self-efficacy in sleep apnea: instrument development and patient perceptions of
      obstructive sleep apnea risk, treatment benefit, and volition to use continuous
      positive airway pressure.
AB  - STUDY OBJECTIVES: The purpose of this study was to evaluate the Self-Efficacy
      Measure for Sleep Apnea (SEMSA) designed to assess adherence-related cognitions.
      DESIGN: Subjects completed the questionnaire prior to the initiation of
      continuous positive airway pressure (CPAP) treatment. Test-retest reliability of
      the instrument was evaluated by having a subset of subjects complete the SEMSA a
      second time at home, 1 week later, returning the questionnaire by mail. PATIENTS:
      213 subjects with newly diagnosed obstructive sleep apnea were recruited from the
      clinic populations of 2 sleep disorders centers. MEASUREMENTS AND RESULTS:
      Content validity was confirmed by a panel of expert judges. Confirmatory factor
      analysis validated the 3 a priori sub-scales: risk perception, outcome
      expectancies, and treatment self-efficacy. The internal consistency of the total
      instrument was 0.92. Test-retest reliability coefficients (N = 20) were estimated
      to be 0.68, P = 0.001, for Perceived Risk; 0.77, P more more than 0.0001, for
      Outcome Expectancies; and 0.71, P = 0.0005, for the Treatment Self-Efficacy
      subscale. Subject responses indicated that approximately half of the subjects did
      not perceive problems with concentration, sexual performance, sleepy driving, or
      an accident as related to sleep apnea. More than 60% of the subjects acknowledged
      most of the benefits of CPAP presented to them, but only 53% associated CPAP use
      with enhanced sexual performance. Frequently identified barriers to treatment use
      were nasal stuffiness, claustrophobia, and disturbing bed partner sleep.
      CONCLUSION: These findings indicate that the SEMSA has strong psychometric
      properties and has the potential for identifying patient perceptions that may
      indicate those most likely to not adhere to treatment.

PMID- 14572129
TI  - Arousal responses to somatosensory and mild hypoxic stimuli are depressed during
      quiet sleep in healthy term infants.
AB  - STUDY OBJECTIVES: To compare arousal responses to somatosensory and hypoxic
      stimuli in sleeping human infants and to determine whether sleep state and
      postnatal age exerted similar changes in these arousal responses. DESIGN: We
      delivered somatosensory (nasal air-jet) stimulation and mild hypoxia (15% oxygen)
      to 10 healthy term infants aged 2 to 4 weeks, 2 to 3 months, and 5 to 6 months
      during identified sleep states. Hypoxic challenges were terminated at arousal,
      when the oxygen saturation fell below 85%, or at 5 minutes (failure to arouse).
      RESULTS: Infants failed to arouse to a greater percentage of hypoxia tests during
      quiet sleep (QS) than during active sleep (AS) at 2 to 3 months and 5 to 6 months
      of age (P < 0.01). Infants failed to arouse to a greater percentage of hypoxic
      challenges during QS at 2 to 3 months and 5 to 6 months than at 2 to 4 weeks of
      age. Arousal latency to hypoxia was significantly longer in QS than in AS at each
      study age; however, arousal latency was not affected by postnatal age. Arousal
      thresholds to somatosensory stimulation were significantly greater in QS than in
      AS, except at 2 to 4 weeks of age. In AS, arousability to the air-jet was greater
      at 2 to 3 months compared to 2 to 4 weeks of age (P < 0.05); in QS it was lower
      at 5 to 6 months compared to 2 to 4 weeks of age (P < 0.05). Arousal latency to
      hypoxia and arousal thresholds to air-jet stimulation were not correlated within
      infants. CONCLUSION: We conclude that arousal responses of infants to
      somatosensory and respiratory stimuli are similarly affected by sleep state and
      postnatal age. Infants are less arousable to both stimulus modalities in QS than
      in AS, and less arousable at 5 to 6 months of age than at 2 to 4 weeks in QS.

PMID- 14572128
TI  - Periodic limb movements in sleep and iron status in children.
AB  - STUDY OBJECTIVES: To assess potential relationships between serum iron and
      ferritin levels and the severity of periodic limb movement in sleep (PLMS) in a
      pediatric population, and to evaluate the response to supplemental iron therapy.
      DESIGN: A prospective study of all consecutively diagnosed children with PLMS
      (periodic limb movement index [periodic limb movements per hour of total sleep
      time, [PLMI] > 5) who underwent overnight polysomnographic evaluation. In all
      patients, complete blood count and serum iron and ferritin levels were obtained.
      Patients with serum ferritin concentrations less than 50 microg/L were prescribed
      iron sulfate at 3 mg/kg of elemental iron per day for 3 months. At the end of
      treatment, serum iron and ferritin levels and sleep studies were repeated.
      SETTING: Comprehensive Sleep Medicine Center, Tulane University Health Sciences
      Center, and Kosair Children's Hospital Sleep Medicine and Apnea Center. PATIENTS:
      Twenty boys and 19 girls with PLMS with a mean age of 7.5 +/- 3.1 years.
      INTERVENTION: Iron therapy. RESULTS: Twenty-eight (71.8%) patients had ferritin
      levels less than 50 microg/L. There was no significant correlation between serum
      ferritin concentration and PLMS severity as indicated by the PLMI (r = -0.19).
      The PLMI in patients with serum ferritin levels less than 50 microg/L (29.9 +/-
      15.5 PLM/h) was higher than in patients with serum ferritin levels greater than
      50 microg/L (21.9 +/- 11.8 PLM/h); however, the difference did not achieve
      statistical significance (P = 0.09). In contrast, serum iron was significantly
      correlated with PLMI (r = -0.43, P < 0.01). Indeed, patients with serum iron
      concentrations less than 50 microg/dL had a higher PLMI compared to patients with
      serum iron concentrations greater than 50 microg/dL (42.8 +/- 18.3 PLM/h and 23.1
      +/- 10.1 PLM/h, respectively; P = 0.02). Twenty-five out of the 28 PLMS patients
      with serum ferritin levels less than 50 microg/L received treatment with iron
      sulfate, and 19 (76%) responded favorably. Among the responders to iron therapy,
      PLMI decreased from 27.6 +/- 14.9 PLM per hour to 12.6 +/- 5.3 PLM per hour after
      3 months of iron supplements (P < 0.001) and coincided with increases in serum
      ferritin levels (pre: 40.8 +/- 27.4 microg/L vs post: 74.1 +/- 13.0 microg/L; P <
      0.001). CONCLUSIONS: In children, the presence of PLMS is frequently associated
      with low serum iron and a tendency toward low serum ferritin levels. In addition,
      iron therapy is associated with clinical improvement in most of these patients.

PMID- 14572130
TI  - Polysomnographic and actigraphic evidence of sleep fragmentation in patients with
      irritable bowel syndrome.
AB  - STUDY OBJECTIVE: To characterize the function and quality of sleep in patients
      with irritable bowel syndrome (IBS). DESIGN: A prospective study with a historic
      comparison group. SETTING: A regional hospital that also serves as a tertiary
      referral center. PATIENTS: Eighteen patients with IBS and a comparison group of
      20 matched adults with mild benign snoring. INTERVENTIONS: A polysomnography
      study and a wrist actigraphy study. MEASUREMENTS: All subjects underwent sleep
      studies and completed self-report questionnaires (IBS severity, psychosocial
      variables, sleep function, and Epworth Sleepiness Scale). Fourteen IBS and 11
      comparison patients underwent actigraphy. RESULTS: The IBS patients had more than
      70% less slow-wave stage sleep (4.5 +/- 7.3% vs 19.3 +/- 12.9%; P = 0.006),
      compensated by increased stage 2 sleep (72.2 +/- 6.6% vs 60.1 +/- 16.8%; P =
      0.01). The IBS group had significant sleep fragmentation with a significantly
      higher arousal and awakening index (P < 0.001), a longer wake period after sleep
      onset (P = 0.02), and more downward shifts to lighter sleep stages (P = 0.01).
      The 4-night actigraphy study supported the polysomnography findings. The sleep
      fragmentation index was significantly higher (P = 0.008) in the IBS group. The
      IBS patients reported greater daytime sleepiness (9.0 +/- 4.8 vs 6.4 +/- 4.8,
      Epworth Sleepiness Scale score, P < 0.01) and greater impairment in quality of
      life, which correlated significantly with the sleep fragmentation indexes. The
      difference between the groups was not due to differences in baseline
      anxiety/depression levels. CONCLUSIONS: Patients with IBS have impaired sleep
      quality, reduced slow-wave sleep activity, and significant sleep fragmentation.
      The cause-and-effect relationship of these findings with patients' daytime
      symptoms should be studied further.

PMID- 14572131
TI  - Practice parameters for using polysomnography to evaluate insomnia: an update.
AB  - Insomnia is a common and clinically important problem. It may arise directly from
      a sleep-wake regulatory dysfunction and/or indirectly result from comorbid
      psychiatric, behavioral, medical, or neurological conditions. As an important
      public-health problem, insomnia requires accurate diagnosis and effective
      treatment. Insomnia is primarily diagnosed clinically with a detailed medical,
      psychiatric, and sleep history. Polysomnography is indicated when a sleep-related
      breathing disorder or periodic limb movement disorder is suspected, initial
      diagnosis is uncertain, treatment fails, or precipitous arousals occur with
      violent or injurious behavior. However, polysomnography is not indicated for the
      routine evaluation of transient insomnia, chronic insomnia, or insomnia
      associated with psychiatric disorders.

PMID- 14572132
TI  - Re: Kaneko Y, Hajek VE, Zivanovic V et al. Relationship of sleep apnea to
      functional capacity and length of hospitalization following stroke. SLEEP
      2003;26(3):293-7.

PMID- 14572133
TI  - The semantics of sleepiness.

PMID- 14572134
TI  - Neurobiology of disease in children: leukodystrophies.

PMID- 14572136
TI  - Metachromatic leukodystrophy: recent research developments.
AB  - Metachromatic leukodystrophy is a lysosomal storage disorder caused by the
      deficiency of arylsulfatase A, causing the storage of the sphingolipid sulfatide.
      The disease is characterized by a progressive demyelination, which results in
      severe, finally lethal, neurologic symptoms. Genetically, the disease is
      heterogeneous, most mutant alleles are private, and only three have a frequency
      worth mentioning. An arylsulfatase A-deficient knockout mouse displays some of
      the disease features seen in patients but does not show the widespread
      demyelination characteristic of the disease. Nevertheless, this animal model was
      used to investigate the therapeutic potential of bone marrow stem cell-based gene
      therapy. Although treated animals show considerable arylsulfatase A activity in
      many tissues, including the brain, the effect on sulfatide storage was
      disappointing. Only in the kidney and liver of animals with very high enzyme
      levels was lipid storage positively affected. In particular, no effect was seen
      in the brain. These results suggest that bone marrow stem cell-based gene therapy
      could be of limited value in the treatment of this disease. The pathogenesis of
      the disease is poorly understood. It is not yet known how sulfatide storage
      negatively affects the metabolism of the oligodendrocyte. The amount and
      distribution of various proteins in the myelin of arylsulfatase A-deficient mice
      were investigated. It was shown that the myelin protein, myelin and lymphocyte
      protein (MAL), is reduced in deficient animals and that the myelin protein
      proteolipid displays an altered distribution within the myelin membranes.
      Possibly, these alterations contribute to the development of demyelination in
      this disease.

PMID- 14572137
TI  - Globoid cell leukodystrophy (Krabbe's disease): update.
AB  - The classic globoid cell leukodystrophy (Krabbe's disease) is caused by genetic
      defects in a lysosomal enzyme, galactosylceramidase. It is one of the two classic
      genetic leukodystrophies, together with metachromatic leukodystrophy. The mode of
      inheritance is autosomal recessive. Typically, the disease occurs among infants
      and takes a rapidly fatal course, but rarer late-onset forms also exist. Clinical
      manifestations are exclusively neurologic with prominent white-matter signs. The
      pathology is unique, consisting of a rapid and nearly complete disappearance of
      myelin and myelin-forming cells--the oligodendrocytes in the central nervous
      system and the Schwann cells in the peripheral nervous system, reactive astroytic
      gliosis, and infiltration of the unique and often multinucleated macrophages
      ("globoid cells") that contain strongly periodic acid-Schiff (PAS)-positive
      materials. A normally insignificant but highly cytotoxic metabolite,
      galactosylsphingosine (psychosine), is also a substrate of galactosylceramidase
      and is considered to play a critical role in the pathogenesis. The
      galactosylceramidase gene has been cloned, and a large number of disease-causing
      mutations have been identified. Equivalent genetic galactosylceramidase
      deficiency occurs in several mammalian species, such as mouse, dog, and monkey.
      Recently, deficiency of one of the sphingolipid activator proteins, saposin A,
      was demonstrated to cause a late-onset, slowly progressive globoid cell
      leukodystrophy at least in the mouse, with all of the phenotypic consequences of
      impaired degradation of galactosylceramidase substrates. Human globoid cell
      leukodystrophy owing to saposin A deficiency might be anticipated and should be
      suspected in human patients with a late-onset leukodystrophy with normal
      galactosylceramidase activity when other possibilities are also excluded. The
      only serious attempt at treating human patients is bone marrow transplantation,
      which can provide significant alleviation of symptoms, particularly in those
      patients with later-onset, more slowly progressive globoid cell leukodystrophy.

PMID- 14572135
TI  - Leukodystrophies: pathogenesis, diagnosis, strategies, therapies, and future
      research directions.

PMID- 14572139
TI  - Metabolic changes in the knockout mouse for Canavan's disease: implications for
      patients with Canavan's disease.
AB  - Canavan's disease is an autosomal recessive disorder caused by aspartoacylase
      deficiency, which leads to accumulation of N-acetylaspartic acid in the brain and
      blood and an elevated level of N-acetylaspartic acid in the urine. The brain of
      patients with Canavan's disease shows spongy degeneration. How the enzyme
      deficiency and elevated N-acetylaspartic acid cause the pathophysiology observed
      in Canavan's disease is not obvious. The creation of a knockout mouse for
      Canavan's disease is being used as a tool to investigate metabolic pathways in
      the mouse and correlate them with the patients with Canavan's disease. The level
      of glutamate is lower in the knockout mouse brain than in the wild-type mouse
      brain, similar to what we have found in children with Canavan's disease, and so
      are the levels of gamma-aminobutyric acid (GABA). The level of aspartate is
      higher in the Canavan's disease mouse brain. The activity of aspartate
      aminotransferase, an enzyme involved in the malate-aspartate shuttle, is lower in
      the Canavan's disease mouse brain. The lower weight of the Canavan's disease
      mouse was in direct proportion to low total-body fat and bone mineral density.
      These changes might be similar to what is seen in patients with Canavan's disease
      and could have therapeutic implications.

PMID- 14572138
TI  - Molecular basis of Canavan's disease: from human to mouse.
AB  - Canavan's disease is an autosomal recessive disorder caused by aspartoacylase
      deficiency. The deficiency of aspartoacylase leads to increased concentration of
      N-acetylaspartic acid in brain and body fluids. The failure to hydrolyze N
      acetylaspartic acid causes disruption of myelin, resulting in spongy degeneration
      of the white matter of the brain. The clinical features of the disease are
      hypotonia in early life, which changes to spasticity, macrocephaly, head lag, and
      progressive severe mental retardation. Although Canavan's disease is panethnic,
      it is most prevalent in the Ashkenazi Jewish population. Research at the
      molecular level led to the cloning of the gene for aspartoacylase and development
      of a knockout mouse for Canavan's disease. These developments have afforded new
      tools for research in the attempts to understand the pathophysiology of Canavan's
      disease, design new therapies, and explore methods for gene transfer to the
      central nervous system.

PMID- 14572140
TI  - Pelizaeus-Merzbacher disease and spastic paraplegia type 2: two faces of myelin
      loss from mutations in the same gene.
AB  - Pelizaeus-Merzbacher disease and X-linked spastic paraplegia type 2 are two sides
      of the same coin. Both arise from mutations in the gene encoding myelin
      proteolipid protein. The disease spectrum for Pelizaeus-Merzbacher disease and
      spastic paraplegia type 2 is extraordinarily broad, ranging from a spastic gait
      in the pure form of spastic paraplegia type 2 to a severely disabling form of
      Pelizaeus-Merzbacher disease featuring hypotonia, respiratory distress, stridor,
      nystagmus, and profound myelin loss. The diverse disease spectrum is mirrored by
      the underlying pathogenesis, in which a blockade at any stage of myelin
      proteolipid protein synthesis and assembly into myelin spawns a unique phenotype.
      The continuing definition of pathogenetic mechanisms operative in Pelizaeus
      Merzbacher disease and spastic paraplegia type 2, together with advances in
      neural cell transplant therapy, augurs well for future treatment of the severe
      forms of Pelizaeus-Merzbacher disease.

PMID- 14572141
TI  - Alexander's disease: clinical, pathologic, and genetic features.
AB  - Alexander's disease, a rare and fatal disorder of the central nervous system,
      most commonly affects infants and young children but can also occur in older
      children and sometimes adults. In infants and young children, it causes
      developmental delay, psychomotor retardation, paraparesis, feeding problems,
      usually megalencephaly, often seizures, and sometimes hydrocephalus. Juvenile
      cases often do not have megalencephaly and tend to have predominant pseudobulbar
      and bulbar signs. In both groups, characteristic magnetic resonance imaging
      findings have been described. In adult cases, the signs are variable, can
      resemble multiple sclerosis, and might include palatal myoclonus. In all cases,
      the examination of brain tissue shows the presence of widely distributed
      Rosenthal fibers. Almost all cases have recently been found to have a
      heterozygous, missense, point mutation in the gene for glial fibrillary acidic
      protein, which provides a new diagnostic tool. In most cases, the mutation
      appears to occur de novo, not being present in either parent, but some adult
      cases are familial.

PMID- 14572142
TI  - Cerebrotendinous xanthomatosis: clinical manifestations, diagnostic criteria,
      pathogenesis, and therapy.
AB  - In this report, we review the clinical, biochemical, pathophysiologic, and
      therapeutic aspects of cerebrotendinous xanthomatosis. We stress the importance
      of early diagnosis and treatment. In addition, we describe our experience in
      treating patients with chenodeoxycholic acid, an essential drug for this disorder
      that is no longer available.

PMID- 14572143
TI  - Leukoencephalopathy with vanishing white matter: from magnetic resonance imaging
      pattern to five genes.
AB  - Leukoencephalopathy with vanishing white matter can be diagnosed on the basis of
      distinct clinical and magnetic resonance imaging (MRI) findings. It is a
      recessively inherited disorder, most often presenting in young children. The
      clinical symptoms include a slowly progressive cerebellar ataxia, spasticity,
      variable optic atrophy, and relatively preserved mental capacities. In addition,
      there are episodes of rapid and major deterioration following infections with
      fever and minor head trauma. These episodes can end in unexplained coma. MRI
      findings suggest that over time there is a progressive vanishing of the abnormal
      white matter, which is replaced by cerebrospinal fluid. We performed a genome
      wide search and localized a gene for vanishing white matter on chromosome 3q27.
      We demonstrated that mutations in the gene EIF2B5 cause the disease. This gene
      encodes one of the five subunits of the translation factor eIF2B. Patients
      without mutations in the EIF2B5 gene were found to be mutated in one of the other
      genes that encode eIF2B subunits: EIF2B1 to EIF2B4.

PMID- 14572144
TI  - Megalencephalic leukoencephalopathy with subcortical cysts.
AB  - Megalencephalic leukoencephalopathy with subcortical cysts is one of the newly
      described white-matter disorders for which recognition has been brought about by
      advances in imaging technology. The essential diagnostic features include
      megalencephaly noted in infancy, motor disability in the form of spasticity,
      ataxia, occasional seizures, mild cognitive decline, and slow progression.
      Magnetic resonance imaging (MRI) shows bilateral extensive white-matter changes
      with cysts in the temporal regions. Based on the clinical and MRI features,
      megalencephalic leukoencephalopathy with subcortical cysts can be distinguished
      from other conditions (ie, Alexander's disease, Canavan's disease,
      glutaricaciduria type I) that present in infancy with megalencephaly.
      Megalencephalic leukoencephalopathy with subcortical cysts is an autosomal
      recessive disorder, and mutations in the MLC1 gene have now been shown to cause
      this condition. Several genotypic and phenotypic variations have been described.
      In India, megalencephalic leukoencephalopathy with subcortical cysts occurs
      predominantly in the Agarwal community. A common mutation in the MLC1 gene has
      been seen in 31 Agarwal patients, which suggests a founder effect.

PMID- 14572145
TI  - The attention-deficit hyperactivity disorder paradox: 2. Phenotypic variability
      in prevalence and cost of comorbidity.
AB  - The objective of this study was to use population-based data to estimate the cost
      and phenotypic variation of conditions comorbid with attention-deficit
      hyperactivity disorder (ADHD). The North Dakota Department of Health's Claims
      Database was used to estimate the administrative prevalence, rates of
      comorbidity, and cost of care for subjects with ADHD. The case population was
      7745 children. We then examined the 10 most frequent comorbidities for a defined
      condition in the International Classification of Diseases-9th edition (ICD-9).
      The observed prevalence of general health conditions was 12 to 70% less than
      expected. The presence of a comorbid condition resulted in increases in costs of
      care of dollar 381 to dollar 731 per case per year. The observed prevalence of
      comorbid mental health conditions was 97 to 5286% higher than expected. The
      prevalence of conditions comorbid with ADHD varies widely, with rates of general
      medical conditions decreased and rates of most mental disorders increased. The
      costs for comorbidity with general health conditions were offset by large
      decreases in prevalence rates compared with controls. We identified an ADHD
      paradox: decreased rates of comorbid general health conditions and increased
      rates of comorbid mental disorders. Further research on comorbidity in ADHD is
      required.

PMID- 14572146
TI  - Introduction for pediatric neurorehabilitation seminars in pediatric neurology.

PMID- 14572147
TI  - Shaking-impact syndrome of infancy.
AB  - Shaking-impact syndrome (SIS) is a leading cause of traumatic brain injury in
      infants and young children. Evaluation of these children requires a detailed
      history and physical examination as well as documentation of intracranial injury
      with neuroimaging, a dilated fundoscopic examination, a skeletal survey and other
      laboratory studies. Debate still exists as to the exact mechanisms of brain
      injury in these patients. The various contributions of shaking alone, shaking
      with impact, and apnea are discussed. Differences of injury type and severity
      between accidental traumatic brain injury and SIS are delineated. The long-term
      neurodevelopmental outcome for survivors of SIS is generally poor. Because few
      treatment options are successful in reducing the morbidity and mortality of this
      syndrome, prevention may be the only reasonable solution.

PMID- 14572148
TI  - Survival rates of children with severe neurologic disabilities: a review.
AB  - Knowledge of accurate survival rates of children with neurologic disabilities is
      important for third-party insurance payers planning future medical expenses. This
      is of particular importance to pediatric skilled nursing facilities (SNFs) that
      depend on financial support from governmental sources. Eyman published survival
      rate results from California that were extremely pessimistic and not in keeping
      with our clinical impressions. This led us to conduct a thorough review of our
      survival rates, which were much better than those reported by Eyman. Since the
      publication of our study, a large number of reports have appeared from many
      different countries, as well as further information from California using an
      expanded database. The survival rate data that we obtained remain consistently
      better than that in most recent reports. In the California results, 10-year
      survival rates for the most-disabled group (group 1) were reported to be 32% in
      1993 and 45% in 1998, compared with 73% in our study. Eight-year survival rates
      for group 1 from California were reported to be 38% in 1993 and 63% in 2000,
      compared with our finding of 73%. The reasons for our better survival rates
      include the fact that all of our patients were in SNFs, where prompt medical care
      for acute illnesses was always provided, whereas only 3.5% of the study group was
      in SNFs in California. Also, the California data contained many methodologic and
      statistical errors, which are reviewed here.

PMID- 14572149
TI  - Recovery from mild head injury in pediatric populations.
AB  - This article provides an overview of the diagnosis, classification, and
      pathophysiology of mild head injury (MHI) in children. The difficulties
      associated with determination of MHI severity are outlined. Also, recently
      published research pertaining to pediatric MHI is reviewed. The recent research
      pertaining to MHI in children is generally consistent with the conclusions
      reached by the authors of the most recent comprehensive review, which reported
      that children who have suffered MHI often experience a symptomatic phase that
      could extend up to a few months, but these symptoms usually resolve. Numerous
      preinjury variables have been identified, including premorbid learning and
      behavior problems, disadvantaged socioeconomic status, premorbid
      neurodevelopmental abnormalities, and adverse family conditions, that appear to
      explain the persistence of some symptoms experienced by a subset of children with
      MHI. Directions for future research are provided.

PMID- 14572150
TI  - Rehabilitation of a child with a spinal cord injury.
AB  - The incidence and sex distribution of spinal cord injury (SCI) changes with age.
      Motor vehicle accidents, bicycle accidents, sports accidents, and violence are
      major causes in the pediatric population. Pulmonary complications may be severe
      and life-threatening in the acute phase. Chronically, the degree of ventilatory
      support needed depends on the level of the injury, with high cervical injuries
      typically requiring life-long ventilatory support. Deep venous thrombosis,
      autonomic dysreflexia, hypercalcemia, heterotopic ossification, spasticity,
      neurogenic bowel and bladder, scoliosis, and pain all may be secondary to SCI.
      Numerous orthotic aids are available for rehabilitation. An integrated
      rehabilitation program may also include spasticity management, a bowel and
      bladder program, and other features geared to the individual patient.

PMID- 14572151
TI  - Epilepsy: habilitation and rehabilitation.
AB  - Rehabilitation represents not only a distinct field of medicine, but also a
      philosophical and practical treatment approach that can be applied to a variety
      of chronic disorders. Neurology encompasses many chronic disorders, making it
      ideal for the application of rehabilitation principles in daily practice.
      Epilepsy offers a unique opportunity to incorporate rehabilitation principles
      into the management of a complex medical disorder. Epilepsy is an evolving
      disease process that changes with the maturation of the central nervous system.
      The rehabilitative model provides the framework for a dynamic treatment plan to
      meet the changing needs of the child with epilepsy through the social and
      developmental changes of childhood, adolescence, and adulthood. The development
      of epilepsy may complicate the recovery from many acute and chronic conditions
      that affect the central nervous system. The rehabilitation process must address
      these many aspects of the disease process and its sequelae. This makes
      neurologists uniquely qualified to manage the rehabilitation team. The impact of
      the therapeutic milieu on the recovery process may be as important as any
      specific medical or surgical intervention.

PMID- 14572152
TI  - Defect of tumour necrosis factor-alpha (TNF-alpha) production and TNF-alpha
      induced ICAM-1-expression in BRCA1 mutations carriers.
AB  - BACKGROUND: Tumour necrosis factor-alpha (TNF-alpha) is a potent cytokine
      secreted primarily by activated cells from the monocyte/macrophage lineage which
      exhibits various antitumoral effects including the induction of apoptosis,
      necrosis, activation of lytic effector cells as well as upregulation of the
      expression of intercellular adhesion molecule-1 (ICAM-1) which is of decisive
      importance in the interaction with lymphokine activated killer cells. Previous
      studies from our laboratory have indicated impaired production of TNF-alpha by
      monocytes as well as decreased expression of ICAM-1 on monocytes derived from
      patients with various stages of breast cancer. METHODS: In the present
      experiments, we have assessed spontaneous as well as lipopolysaccharide (LPS)
      induced production of TNF-alpha by as well as expression of ICAM-1 on monocytes
      derived from healthy females with germline mutations of BRCA1 and from healthy
      age-matched control females. RESULTS: We report that monocytes derived from
      healthy women with various germline mutations of BRCA1 had significantly
      decreased spontaneous (p = 0.03) and LPS-induced (p < 0.001) production of TNF
      alpha, as compared to monocytes derived from healthy age-matched control females.
      In contrast, no difference in LPS- or TNF-alpha-induced production of interleukin
      6 was found. Whereas unstimulated monocytes derived from healthy women with
      germline mutations of BRCA1 and from healthy control women had similar expression
      of ICAM-1, stimulation with cytokines TNF-alpha and/or interleukin-1 led to a
      significant increase of ICAM-1 expression on monocytes derived from control
      females only, but not from BRCA1 germline mutation carriers (p < 0.001).
      CONCLUSION: We conclude that the presence of germline mutations of BRCA1 was
      associated with a selective deficiency in spontaneous and LPS-induced production
      of TNF-alpha and of TNF-alpha-induced ICAM-1 expression on peripheral blood
      monocytes.

PMID- 14572153
TI  - Mammography surveillance following breast cancer.
AB  - BACKGROUND: To describe when women diagnosed with breast cancer return for their
      first mammography, and to identify factors predictive of women returning for
      mammographic surveillance. METHODS: Women who underwent mammography at facilities
      participating in the National Cancer Institute's Breast Cancer Surveillance
      Consortium (BCSC) during 1996 and who were subsequently diagnosed with ductal
      carcinoma in situ or invasive breast cancer were included in this study. Data
      from seven mammography registries were linked to population-based cancer and
      pathology registries. Kaplan-Meier curves were used to depict the number of
      months from the breast cancer diagnosis to the first mammogram within the defined
      follow-up period. Demographic, disease and treatment variables were included in
      univariate and multivariate analyses to identify factors predictive of women
      returning for mammography. RESULTS: Of the 2503 women diagnosed with breast
      cancer, 78.1% returned for mammography examination between 7 and 30 months
      following the diagnosis. Mammography facilities indicated that 66.8% of
      mammography examinations were classified as screening. Multivariate analyses
      found that women were most likely to undergo surveillance mammography if they
      were diagnosed at ages 60-69 with Stage 0, I or II breast cancer and had received
      radiation therapy in addition to surgery. CONCLUSIONS: While the majority of
      women return for mammographic surveillance following breast cancer, some
      important subgroups of women at higher risk for recurrence are less likely to
      return. Research is needed to determine why some women are not undergoing
      mammography surveillance after a breast cancer diagnosis and whether surveillance
      increases the chance of detecting tumors with a good prognosis.

PMID- 14572154
TI  - Autocrine signalling through erbB receptors promotes constitutive activation of
      protein kinase B/Akt in breast cancer cell lines.
AB  - The protein kinase PKB/Akt plays a pivotal role in promoting cell survival and
      proliferation. This study investigated the regulation of PKB/Akt activity in
      breast cancer cells. In primary invasive breast cancers PKB/Akt exhibited
      elevated phosphorylation at regulatory site Ser473 in 80% of cases, using
      immunohistochemistry. The degree of phospho-PKB/Akt immunoreactivity was
      positively correlated with the extent of its nuclear accumulation.
      Moderate/strong staining was seen in 31% of the samples but was absent in tumour
      associated normal breast epithelia. To examine the mechanisms of PKB/Akt
      activation, we studied its phosphorylation in a panel of breast cancer cell
      lines. PKB/Akt was constitutively phosphorylated on both regulatory sites (Thr308
      and Ser473) in the absence of serum growth factors in 7 of 8 lines but not in two
      cell lines derived from normal breast epithelia. Further analysis revealed that
      constitutive PKB/Akt phosphorylation was associated with loss of PTEN phosphatase
      expression (CAL51, MDA-MB-468, BT549 cells) and constitutive activation of erbB2
      (SKBR3, BT474 cells). In two further breast cancer lines (T47D and HS578T)
      PKB/Akt phosphorylation was dependent upon autocrine factors acting primary
      through the epidermal growth factor receptor (EGFR) and erbB2. Conditioned medium
      from HS578T cells stimulated EGFR-dependent PKB/Akt phosphorylation in normal
      breast cells. These results demonstrate that PKB/Akt is frequently activated in
      breast cancer through diverse mechanisms, including autocrine signalling via erbB
      receptors.

PMID- 14572155
TI  - Oral contraceptives and the risk of ductal breast carcinoma in situ.
AB  - Recent evidence suggests that oral contraceptive use is associated with little to
      no increased risk of invasive breast carcinoma. No study has examined the
      relationship between oral contraceptive use and the risk of non-invasive breast
      carcinoma, that is, breast carcinoma in situ. OBJECTIVE: To define the role of
      oral contraceptive use in the development of breast carcinoma in situ. METHODS:
      The data are 875 ductal carcinoma in situ (DCIS) cases diagnosed among residents
      of the state of Connecticut from September 15, 1994 to March 14, 1998 and between
      the age of 20 and 79 years as well as 999 control subjects. Controls are female
      Connecticut residents collected via random-digit-dial and frequency matched to
      the cases by 5-year age intervals. Telephone interviews were used to collect
      information on risk factors and cancer screening history. Logistic regression was
      used to provide maximum likelihood estimates of the odds ratios (OR) with 95%
      confidence intervals (95% CI). RESULTS: The risk of being diagnosed with DCIS for
      women who had ever used oral contraceptives was not increased relative to women
      who had never used them (OR: 1.0, 95% CI: 0.8, 1.2). The risk did not
      significantly increase with duration of oral contraceptive use, nor with duration
      of high estrogen use, time since last use, progestin or estrogen type, or age at
      first use. Furthermore, the association between oral contraceptive use and DCIS
      risk did not vary by the presence of a family history of breast cancer or by
      menopausal status. CONCLUSIONS: In these data, no evidence was found for an
      increased risk of ductal carcinoma in situ associated with the use of oral
      contraceptives.

PMID- 14572156
TI  - The presence of a fibrotic focus in invasive breast carcinoma correlates with the
      expression of carbonic anhydrase IX and is a marker of hypoxia and poor
      prognosis.
AB  - The value of the fibrotic focus (FF) as a marker of intra-tumoral hypoxia in
      invasive breast carcinoma was assessed by studying its relationship with the
      expression of the hypoxia-induced carbonic anhydrase IX (CA IX), angiogenesis
      indices and prognosis. CA IX expression was immunohistochemically detected in 2
      independent study groups, totaling 184 patients, and correlated with tumor
      characteristics, angiogenesis related parameters and patient outcome by
      univariate analysis. CA IX immunostaining scores in carcinoma cells and in
      tumoral fibroblasts were significantly higher in expansively growing tumors (p =
      0.0001 and p < 10(-4), respectively), containing an FF (p = 0.0004 and p < 10(
      4)) and showing high histological grade (p = 0.016 and p = 0.0006). Microvessel
      density, quantified by Chalkley counting, was correlated with CA IX expression
      both in the carcinoma cells and in the fibroblasts (p = 0.0076 and p = 0.0025)
      and with the presence and relative size of an FF (p = 0.006). The fraction of
      proliferating endothelial cells was positively correlated with CA IX scores in
      the fibroblasts (r = 0.4, p = 0.02) and with the presence of an FF (p = 0.02). CA
      IX scores in the fibroblasts--and to a lesser extent in the carcinoma cells--were
      associated with a higher relapse rate (p = 0.006) and a worse overall survival (p
      = 0.003). The highest CA IX immunostaining scores were found in the fibroblasts
      of large FF occupying more than one-third of the tumor. A large FF was associated
      with worse overall survival in a consecutive patient group (p = 0.01) and with
      shorter disease-free (p = 0.02) and overall survival (p = 0.0005) in T1-2N0
      breast cancer patients. The strong association of CA IX expression with the
      presence of an FF shows that the latter is a marker of intra-tumoral hypoxia. FF
      is useful as a surrogate marker of hypoxia-driven ongoing angiogenesis and is
      associated with a higher relapse rate and a worse overall survival.

PMID- 14572157
TI  - Expression of MRP1, LRP and Pgp in breast carcinoma patients treated with
      preoperative chemotherapy.
AB  - Our purpose was to determine the expression of the drug resistance factors
      multidrug resistance protein (MRP1), lung resistance protein (LRP) and P
      glycoprotein (Pgp) in breast carcinoma patients treated with preoperative
      chemotherapy. We have studied the expression of these proteins in breast
      carcinomas by immunohistochemistry both prior (n = 80) and after (n = 68)
      preoperative chemotherapy and compared their expression with response to
      preoperative chemotherapy. In paired samples prior and after chemotherapy
      expression of drug resistance factors was significantly lower in prechemotherapy
      samples as compared with postchemotherapy specimens. This was observed for MRP1
      (62% vs. 88%, P < 0.001), LRP (65% vs. 97%, P < 0.001) and Pgp (55% vs. 100%, P <
      0.001). Prechemotherapy expression of MRP1 was more frequently observed in
      patients with distant metastases than in those without (50% vs. 8%, P = 0.02). No
      associations were observed between LRP expression and clinical parameters. Pgp
      expression was more frequently detected in lobular carcinomas than in ductal
      carcinomas (93% vs. 46%, P = 0.001) and in patients with positive lymph nodes
      than in patients with negative lymph nodes (65% vs. 31%, P = 0.008) but was
      independent of other clinical parameters. No significant associations were found
      between the prechemotherapy or postchemotherapy expression of either of these
      three proteins and response to preoperative chemotherapy. However,
      prechemotherapy MRP1 expression was significantly associated with shorter
      progression-free survival of the patients (P = 0.02), whereas no such
      associations were observed for either LRP or Pgp. In conclusion, preoperative
      chemotherapy increases the expression of MRP1, LRP and Pgp. Response to
      chemotherapy is not associated with pre- or postchemotherapy expression levels of
      these drug resistance proteins but time to progression may be influenced by
      prechemotherapy MRP1 expression.

PMID- 14572158
TI  - Evaluation of the prognostic role of vascular endothelial growth factor and
      microvessel density in stages I and II breast cancer patients.
AB  - In this study, we retrospectively evaluated the expression of vascular
      endothelial growth factor (VEGF) and microvessel density (MVD) in 228 and 213
      specimens, respectively, from stages I and II breast cancer patients (pts)
      enrolled in a randomized phase III adjuvant chemotherapy trial comparing
      epirubicin to CMF, while tamoxifen was given to all postmenopausal pts. The
      expression of VEGF and MVD was assessed on tissue sections formalin-fixed and
      paraffin-embedded by immunohistochemical staining using anti-VEGF antibody of
      human origin and anti-CD34 monoclonal antibody. Univariate and multivariate
      analysis were performed using chi squared test, log-rank test and Cox's
      regression model. Sixty four of 228 pts were classified as VEGF positive (28%)
      with no significant difference in the two treatment arms. In 213 pts evaluated
      for CD34, 103 pts (48%) were classified as MVD high. No significant association
      between VEGF and MVD was found, and neither were they correlated with many known
      prognostic factors such as age, tumor size, nodal status, and histological grade.
      The only significant correlations observed were between VEGF and estrogen
      receptor (ER) status (p = 0.013) and between MVD and HER2 overexpression (p =
      0.023). At a median follow up of 96 months VEGF and MVD were not correlated with
      relapse-free survival (RFS) and overall survival (OS) in all pts and in pts
      assigned to one of the two treatment arms. In conclusion, VEGF and MVD
      retrospectively evaluated, cannot be considered prognostic factors in node
      negative (N-) high risk and node positive (N+) breast cancer pts treated with two
      different regimens of adjuvant chemotherapy.

PMID- 14572159
TI  - The common 677C>T gene polymorphism of methylenetetrahydrofolate reductase gene
      is not associated with breast cancer risk.
AB  - Methylenetetrahydrofolate reductase (MTHFR) is involved in folate metabolism and
      plays a role in DNA biosynthesis, methylation, and repair in actively dividing
      cells. A common 677C>T polymorphism in the gene for MTHFR, leading to a
      thermolabile enzyme with decreased activity, has been associated with reduced
      plasma folate levels and elevated homocysteine levels and could be a risk factor
      for breast cancer. In the present case-control study, MTHFR genotype was
      determined in 500 women with clinically verified breast cancer and 500 female age
      matched healthy control subjects. The homozygous TT genotype was found in 13.0%
      patients and 13.1% controls (P = n.s.). The odds ratio of TT homozygotes for
      breast cancer was 0.99 (95% confidence interval 0.68-1.43). The MTHFR genotype
      was furthermore not associated with tumor size, histological grading, estrogen or
      progesterone receptor status and age at diagnosis. In a subgroup of 116
      premenopausal patients, no increased frequency of the homozygous 677T genotype
      was found (13.8%). Therefore, we conclude that the MTHFR 677C>T polymorphism is
      not associated with individual susceptibility to breast cancer.

PMID- 14572160
TI  - Functional genomics and radioisotope-based imaging procedures.
AB  - After the sequencing of the human genome has been completed, non-invasive imaging
      studies are needed to assess the function of new genes in living organisms. The
      evaluation of genetically manipulated animals or new designed biomolecules will
      require a thorough understanding of physiology, biochemistry and pharmacology,
      and the experimental approaches will involve many new technologies including in
      vivo imaging with single photon emission computed tomography (SPECT) and positron
      emission tomography (PET). Nuclear medicine procedures may be applied for the
      determination of gene function and regulation using established and new tracers
      or using in vivo reporter genes such as enzymes, receptors, antigens or
      transporters. Pharmacogenomics will identify new surrogate markers for therapy
      monitoring which may represent potential new tracers for imaging. Also, drug
      distribution studies for new therapeutic biomolecules are needed at least during
      preclinical stages of drug development. Clinical gene therapy needs non-invasive
      tools to evaluate the efficiency of gene transfer. These informations can be used
      for therapy planning, follow-up studies in treated tumors and as an indicator of
      prognosis. Therapy planning is performed by the assessment of gene expression for
      example using radio-labeled specific substrates to determine the activity of
      suicide enzymes such as the Herpes Simplex Virus thymidine kinase. Follow-up
      studies with single photon emission tomography or positron emission tomography
      may be done to evaluate early or late effects of gene therapy on tumor metabolism
      or proliferation. Finally, new biomolecules will be developed by bioengineering
      methods which may be used for isotope-based diagnosis and treatment of disease.

PMID- 14572161
TI  - Oxygen sensing in cancer.
AB  - Hypoxia is prevalent in many tumours and is prognostically important. A
      transcriptional pathway controlled by hypoxia-inducible factor-1 (HIF) is also
      commonly up-regulated in cancer, resulting in the induction of genes with both
      pro- and anti-tumourigenic properties. High HIF levels may arise as a response to
      the tumour micro-environment or because of genetic events, including mutations
      affecting the von Hippel-Lindau tumour suppressor protein. Recent elucidation of
      mechanisms underlying the regulation of HIF, via amino acid hydroxylases,
      suggests a role in balancing energy production, iron metabolism and oxygen
      supply. Co-selection of properties linked by the HIF pathway may explain the
      glycolytic phenotype of tumours and underlie tumour angiogenesis, which though
      benefiting the tumour as a whole is unlikely to be directly selected at the
      clonal level because it will not give one cell specific advantage over its
      neighbours.

PMID- 14572162
TI  - Cell cycle control, DNA damage checkpoints and cancer.
AB  - DNA damage checkpoints are essential control points in the cell cycle ensuring
      effective damage repair. The loss of checkpoint functions leads to loss of
      genomic integrity and allows accumulation of genetic damage in the daughter
      cells. Checkpoint deficiency is one of the main causes of DNA aberrations in
      cancer.

PMID- 14572164
TI  - Leukemia-lymphoma cell lines as model systems for hematopoietic research.
AB  - Continuous human leukemia-lymphoma (LL) cell lines comprise a rich self-renewing
      resource of accessible and manipulable living cells which has illuminated the
      pathophysiology of hematopoietic tumors as well as basic cell biology. The major
      key advantages of continuous cell lines are the unlimited supply and worldwide
      availability of identical cell material and their cryopreservation. LL cell lines
      are characterized generally by monoclonal origin and differentiation arrest,
      sustained proliferation in vitro with preservation of most cellular features, and
      specific genetic alterations. The most practical classification of LL cell lines
      assigns them to one of the physiologically occurring cell lineages, based on
      their immunophenotype, genotype and functional features. Truly malignant cell
      lines may be distinguished from Epstein-Barr virus (EBV)-immortalized normal
      cells, using various operational and conceptual parameters. The characterization
      and publication of new LL cell lines provides important and informative core data
      which, by opening new avenues for investigation, have become ubiquitous powerful
      research tools that are available to every investigator by reference cell
      repositories. There is a need in the scientific community for clean and
      authenticated LL cell lines to which every scientist has access as offered by
      these institutionalized public cell line banks. A list of the most useful, robust
      and freely available reference cell lines is proposed in this review. Clearly,
      studies of LL cell lines have provided seminal insights into the biology of
      hematopoietic neoplasia.

PMID- 14572165
TI  - Combined oral contraceptives and the risk of myocardial infarction.
AB  - The studies on the combined oral contraceptive (COC) pill and myocardial
      infarction are reviewed. A reasonable conclusion is that the COC pill causes a
      two-fold increase in the risk of myocardial infarction. There is a marked
      interaction with smoking. The pill causes coagulation changes and affects
      lipoprotein and carbohydrate metabolism and these changes provide a plausible
      explanation for its effect. However, there are dangers in using these surrogate
      end-points to predict which pills carry the greatest risk. This must depend on an
      assessment of the epidemiology, and at present third generation pills have not
      convincingly been shown to be safer in this regard. The risk of causing
      myocardial infarction in non-smokers is small but we should be wary of
      prescribing the pill to smokers over 34 years old and especially to smokers over
      39 years old.

PMID- 14572163
TI  - A novel pleiotropic effect of statins: prevention of cardiac hypertrophy by
      cholesterol-independent mechanisms.
AB  - Cardiac hypertrophy is an initial physiological adaptive response by the heart to
      pressure overload. However, if pressure overload persists, frequently, the heart
      decompensates and develops 'pathophysiological' hypertrophy. This leads to
      increased mortality and morbidity and is an independent risk factor for heart
      failure. Because cardiac myocytes convert this pressure overload into
      intracellular biochemical signals, blocking this critical signaling pathway may
      be an important therapeutic target to prevent cardiac hypertrophy. Small GTP
      binding proteins, in particular Rac1, have been suggested to play a key role in
      the development of cardiac hypertrophy. Recently, 3-hydroxyl-3-methylglutaryl
      coenzyme A (HMG-CoA) reductase inhibitors, also called statins, have been shown
      to inhibit cardiac hypertrophy independent of their cholesterol lowering
      property. Statins block the isoprenylation and activation of members of the Rho
      family, such as RhoA and Rac1. Rac1 also regulates NADPH oxidase, which is a
      major source of reactive oxygen species (ROS) in cardiovascular cells. Growing
      evidence suggests that ROS may be involved in the process of cardiac hypertrophy
      and recent research has shown that statins attenuate oxidative stress through
      inhibition of Rac1. Overall, these pleiotropic effects of statins will give new
      insights into the process of cardiac hypertrophy.

PMID- 14572166
TI  - Do all adults with growth hormone deficiency require growth hormone treatment?
AB  - Adult growth hormone (GH) deficiency results mainly from pituitary or peri
      pituitary disease and/or its treatment and is frequently accompanied by other
      anterior pituitary hormone deficiencies. GH deficiency (GHD) results in a number
      of psychological and physical symptoms and signs which in combination constitute
      the adult 'GHD syndrome'. The psychological symptoms include decreased energy
      levels, social isolation, and lack of positive well being, depressed mood and
      increase in anxiety. The physical symptoms and signs include abnormal body
      composition with reduced lean body mass, increased central adiposity, and
      decreased extracellular fluid volume, decreased bone mineral density with an
      increased risk of fracture, reduced muscle strength, reduced exercise capacity,
      increased LDL cholesterol and reduced insulin sensitivity. Hypopituitarism and
      GHD are associated with an increased standardised mortality ratio. The diagnosis
      of GHD is confirmed by the insulin tolerance test or alternative stimulation test
      in the presence of structural pituitary disease and/or additional pituitary
      hormone deficiencies. Replacement with synthetic growth hormone by once daily
      subcutaneous injection can reverse many of the symptoms and signs of growth
      hormone deficiency, but the long-term effects are yet to be established. Whether
      or not all patients with GHD should receive GH replacement remains a matter for
      debate: a selective approach to therapy based on psychological well being and
      quality of life has been adopted in many centres.

PMID- 14572167
TI  - The physiological function of the agouti-related peptide gene: the control of
      weight and metabolic rate.
AB  - The central melanocortin system plays an important role in the regulation of
      energy homeostasis both in rodents and humans, and melanocortin receptors appear
      to be the core of this system. Alpha-melanocyte-stimulating hormone (alpha-MSH)
      inhibits feeding through melanocrtin 3 and 4 receptors (MC3-R and MC4-R) as an
      endogenous agonist. Although mutations in the agouti gene cause an over
      expression of agouti peptide which antagonizes effects of alpha-MSH at MC4-R in
      the brain and causes obese phenotypes, there was no evidence for the presence of
      an endogenous antagonist for MC3-R and MC4-R until agouti related protein (AGRP)
      was identified. AGRP is expressed primarily in the hypothalamic arcuate nucleus
      and central administration of AGRP stimulates feeding and weight gain, and
      decreases metabolic rate. Although a complete deletion of the AGRP gene does not
      produce any significant metabolic phenotypes, reduction in AGRP expression by RNA
      interference is associated with increased metabolic rate along with reduced
      weight gain. The currently available data suggest that elevated AGRP mRNA along
      with reduced proopiomelanocortin (POMC) mRNA is associated with many types of
      obesity and agents antagonizing the effect of AGRP may be a potential therapeutic
      target in treating obesity and obesity-associated disorders in which endogenous
      hypothalamic AGRP is elevated.

PMID- 14572168
TI  - The role of titin in muscular disorders.
AB  - Titin, the biggest single (poly) peptide found in humans, and throughout nature
      so far, was long considered as a good candidate for inherited muscle diseases.
      However, disease-causing defects were not known until recently, when this central
      sarcomeric protein was associated with human skeletal tibial muscular dystrophy
      (TMD/LGMD2J), dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM).
      Several mutations in different parts of titin have now been identified and more
      are expected. Spontaneous mouse and zebrafish mutants have also been reported.
      Experimental knock-outs are not viable, even in cases where just a c-terminal
      part of the gene was silenced, telling something of the basic importance of titin
      for life. In this article we review the current known structure and functions of
      this elementary molecule with some emphasis on the only defects so far known to
      cause human skeletal muscle disease, mutations in the c-terminal M-line part of
      titin.

PMID- 14572169
TI  - Contribution of apo CIII reduction to the greater effect of 12-week micronized
      fenofibrate than atorvastatin therapy on triglyceride levels and LDL size in
      dyslipidemic patients.
AB  - BACKGROUND: Apolipoprotein (apo) CIII plays an important role in the catabolism
      of triglyceride-rich lipoproteins as it is a potent inhibitor of lipoprotein
      lipase (LPL). A low LPL activity has been simultaneously associated with
      hypertriglyceridemia, low HDL cholesterol and with small LDL particles. AIM: To
      compare the effects of a 12-week treatment with micronized fenofibrate (200 mg)
      versus atorvastatin (10 mg) on apo CIII and lipoprotein-lipid levels including
      LDL size. METHOD: After a 4-week washout period, dyslipidemic patients were
      randomized to either micronized fenofibrate (n = 64) or atorvastatin (n = 72).
      RESULTS: Both fenofibrate and atorvastatin significantly decreased apo CIII
      levels by -0.03 +/- 0.03 versus -0.01 +/- 0.03 g/l respectively, and increased
      LDL size by 4.9 +/- 3.3 versus 1.8 +/- 2.9 A. Improvements in these parameters
      were significantly greater with fenofibrate (P < 0.0001). Significant
      relationships were found between changes in triglycerides and changes in apo CIII
      (r = 0.81 and r = 0.59, P < 0.0001) as well as between changes in LDL size and
      changes in apo CIII (r = -0.41 and r = -0.45, P < 0.001), in both fenofibrate and
      atorvastatin groups. respectively. CONCLUSION: The substantial reduction in apo
      CIII induced by micronized fenofibrate plays an important role in the greater
      effect of micronized fenofibrate than atorvastatin on plasma triglycerides and
      LDL size.

PMID- 14572170
TI  - Effects of chloroquine on smooth muscle contracted with noradrenaline or high
      potassium solutions in the rat thoracic aorta.
AB  - The effects of chloroquine on the smooth muscle of isolated rat aortic segments
      were investigated in preparations contracted with either noradrenaline or high
      potassium. At rest, chloroquine (up to 10(-4) M) produced no mechanical response,
      while noradrenaline (10(-6) M) produced a sustained contraction. In the presence
      of 10(-4) M chloroquine, however, the amplitude of contractions produced by
      noradrenaline was attenuated by about 70%, with no alteration of the resting
      tension. In preparations contracted either with noradrenaline or with high-K
      solutions, chloroquine produced a concentration-dependent relaxation. The tension
      decreased below resting level as a result of the co-application of these
      stimulants. The relaxing actions of chloroquine were not altered by methylene
      blue (an inhibitor of guanylate cyclase), suggesting that the cyclic GMP-related
      mechanism was not involved. The ratio of the amplitude of chloroquine-induced
      relaxation was similar in contractions produced by different concentrations of
      potassium ions, suggesting that chloroquine did not cause relaxation as a result
      of membrane hyperpolarization. These results suggest that the inhibition of
      aortic smooth muscle contraction caused by chloroquine is different to that
      produced by endothelium-derived vasodilating factors. It is possible that the
      inhibition of aortic smooth muscle contraction by chloroquine involves modulation
      of the contractile systems and of their regulatory proteins.

PMID- 14572171
TI  - The beta3-adrenoceptor-mediated relaxation induced by dopamine in guinea pig
      taenia caecum.
AB  - The mechanisms of the beta-adrenoceptor-mediated relaxation induced by dopamine
      in guinea pig taenia caecum were examined. The relaxant response to dopamine was
      unaffected by propranolol (10(-8)-10(-5) M) or phentolamine (10(-8)-10(-5) M).
      Atenolol (3 x 10(-7)-3 x 10(-4) M), butoxamine (10(-7)-10(-4) M), prazosin (10(
      8)-10(-5) M), yohimbine (10(-8)-10(-5) M), SCH 23390 (10(-8)-10(-5) M) and
      haloperidol (10(-8)-10(-5) M) had no effect on the potency of dopamine. The
      response to dopamine was antagonized in a concentration-dependent manner by
      bupranolol (3 x 10(-6)-3 x 10(-5) M), and Schild plot of the data revealed the
      pA2 value of 5.55 and the slope of the regression line was 1.13. These results
      suggest that the relaxant response to dopamine in the guinea pig taenia caecum is
      mainly mediated by the beta3-adrenoceptors.

PMID- 14572172
TI  - Lack of cyclic nucleotide regulation of MBCQ-induced relaxation of rat ileal
      smooth muscle.
AB  - The effects of the type V phosphodiesterase (PDE V) inhibitors, MBCQ, zaprinast
      and dipyridamole, on the relationship between relaxation and cyclic nucleotide
      content were investigated in rat ileal smooth muscle. Each of MBCQ (0.01-10
      microM), zaprinast (0.1-100 microM) and dipyridamole (0.1-100 microM) inhibited
      carbachol (CCh; 10 microM)-induced contractions in a concentration-dependent
      manner. When compared with the concentrations of these agents producing 50%
      relaxation (IC50) of CCh-induced contraction, MBCQ was 14-20 fold more potent
      than the other agents. The inhibitory potency of these agents against high K+ (65
      mM KCl)-induced contractions were similar to that for CCh. MBCQ (1, 10 microM)
      did not significantly increase the cGMP content above control levels in the
      presence of CCh (10 microM). Both Zaprinast (1-100 microM) and dipyridamole (1
      100 microM) increased the cGMP content of smooth muscle preparations in a
      concentration-dependent manner. There was a positive correlation between the
      inhibition of the CCh-induced contraction and the increase in cGMP content
      elicited by zaprinast and dipyridamole (zaprinast; r=0.72, P<0.05, dipyridamole;
      r=0.92, P<0.05). However, MBCQ at a concentration which induced a medium-sized
      relaxation did not significantly increase the cGMP content. Neither MBCQ,
      zaprinast nor dipyridamole significantly increased the cAMP content of the
      preparations above control. In summary, it is suggested that the inhibition of
      CCh-induced contractions by zaprinast and dipyridamole involves increases in cGMP
      content via inhibition of PDE V. However the inhibition of CCh-induced
      contraction by MBCQ may not involve cyclic nucleotides in rat ileal smooth
      muscle.

PMID- 14572173
TI  - Effects of nifedipine and nickel on plateau potentials generated in submucosal
      interstitial cells distributed in the mouse proximal colon.
AB  - The effects of nifedipine and nickel ions (Ni2+), known inhibitors of L- and T
      type voltage-gated Ca-channels respectively, were investigated on plateau
      potentials recorded from submucosal interstitial cells distributed in the mouse
      proximal colon. Plateau potentials were generated at a frequency of about 15
      times min(-1) and were formed of two components. The primary component had an
      initial fast rate of rise with a transient potential (rate of rise, 130 mV/s;
      peak amplitude, 35 mV) and was followed by a secondary plateau component with a
      sustained potential (amplitude, 25 mV; duration, 2.6 s). Each cell from which
      recordings were made was injected with neurobiotin. Subsequent morphological
      examination with a confocal microscope indicated successful visualization of
      injected cells only in the presence of 18beta-glycylrhetinic acid (an inhibitor
      of gap junctional connections), suggesting that these cells were dye-coupled with
      surrounding cells. The cells injected with neurobiotin exhibited an oval-shaped
      cell body with bipolar processes and were distributed in the submucosal layer,
      suggesting that they were submucosal interstitial cells of Cajal (ICC-SM). The
      plateau potentials were not altered by 0.01 microM nifedipine, but were reduced
      in duration by 0.1 microM nifedipine, and abolished by 1 microM nifedipine. The
      rate of rise of plateau potentials, but not their amplitude, was reduced by Ni2+
      (> 10 microM), with no significant alteration of the membrane potential. In the
      presence of 100 microM Ni2+, the plateau potentials were changed to a triangular
      form. Thus, the plateau potentials were formed by two types of voltage-gated
      channel current: the initial component was produced by a Ni2+-sensitive channel
      current and the plateau component by a nifedipine-sensitive current. The possible
      involvement of two different types of voltage-gated Ca2+-channels in the
      generation of submucosal pacemaker potentials was discussed.

PMID- 14572174
TI  - The ripple effects of a restrictive Medicaid formulary.

PMID- 14572176
TI  - Better bone density reporting: T-score report versus fracture risk report with
      outcome analysis.
AB  - OBJECTIVE: To determine whether different classification systems for bone
      fracture risk result in different diagnoses and treatments. STUDY DESIGN:
      Assessment of 2 diagnostic classification systems by physicians who routinely
      read bone density scans, using a survey administered by an audience response
      system. METHODS: At a professional meeting, 103 rheumatologists were asked to
      read bone density results from 9 case studies in 2 formats: a standard format
      using T-scores and a format using absolute fracture risk. As physicians were
      shown each of the 18 scans, they diagnosed each patient with (1) normal bone, (2)
      osteopenia, (3) osteoporosis, or (4) unknown, and provided a treatment
      recommendation. Test scans included hip dual-energy x-ray absorptiometry (DEXA)
      (60%), spine DEXA (10%), phalangeal DEXA (10%), and calcaneal ultrasound (20%).
      RESULTS: Approximately 1850 anonymous responses were recorded. For women,
      diagnostic agreement between physicians was 17% for the T-score report and 89%
      for the absolute risk report (P < .001). For men, diagnostic agreement also was
      better with the absolute risk report (66% vs 10%; P < .001). With DEXA, overall
      diagnostic agreement improved from 30% to 68% with the absolute risk report (P <
      .001). With ultrasound, diagnostic agreement improved from 4% to 63% with the
      absolute risk report (P < .001). Bisphosphonates were more likely to be
      prescribed in cases of increasing age and risk if scans were reported in terms of
      absolute fracture risk. CONCLUSION: A direct, risk-based bone density assessment
      may improve consistency and efficiency of diagnosis and treatment of
      osteoporosis.

PMID- 14572175
TI  - A clinical decision and economic analysis model of cancer pain management.
AB  - OBJECTIVE: To design a model that educates clinical decision makers and
      healthcare professionals about the burden of cancer pain in their individual
      populations, and that assists them in weighing the effectiveness and cost of
      different cancer pain management strategies. STUDY DESIGN: Tailored cost
      effectiveness analysis using an evidence-based decision analytic model. METHODS:
      The spreadsheet-based model compares 3 strategies: (1) guideline-based care
      (GBC), (2) oncology-based care (OBC), and (3) usual care (UC). The model
      calculates the likelihood of cancer pain in a healthcare population, how
      effectively that pain is managed, and the average monthly cost of medications
      plus procedural interventions. Model inputs were derived from published US
      population demographics, cancer registry data, high-quality studies of cancer
      pain management, standard reimbursement schedules, and expert opinion. The model
      permits users to tailor population demographics, strategy effectiveness, and
      resource costs. RESULTS: Of 100 000 patients with typical US demographics,
      approximately 508 (0.51%) will have cancer and 205 (0.20%) will suffer from
      cancer pain. After 1 month, the percentage of cancer pain patients with effective
      pain management and the cost of each strategy were estimated as follows: (1) GBC,
      80% and dollar 579; (2) OBC, 55% and dollar 466; and (3) UC, 30% and dollar 315.
      Compared with OBC, GBC had an incremental cost-effectiveness ratio of dollar 452
      per additional patient relieved of cancer pain. Compared with UC, OBC had an
      incremental cost-effectiveness ratio of dollar 601 per additional patient
      relieved of cancer pain. CONCLUSION: Guideline-based cancer pain management leads
      to improved pain control with modest increases in resource use.

PMID- 14572177
TI  - Smoking status identification: two managed care organizations' experiences with a
      pilot project to implement identification systems in independent practice
      associations.
AB  - OBJECTIVE: To determine whether managed care organizations (MCOs) can effectively
      promote the sustained use of smoking status identification systems among
      independent practice associations. STUDY DESIGN: Quasi-experimental design
      measuring smoking status documentation before and after an intervention. METHODS:
      A chart review of the MCOs' patients at 4 participating primary care clinics
      determined the baseline for smoking status documentation before intervention.
      Baseline data were unavailable from a fifth participating clinic. Two quality
      improvement personnel were sent by the MCOs to help the clinics chose and
      implement a system for identifying smoking status. All of the clinics chose a
      sticker system. The change in smoking status documentation was assessed by chart
      reviews of patients enrolled in the MCOs who were seen during the period between
      3 and 16 months after implementation of the system. RESULTS: Following the
      intervention, a significant increase in smoking status documentation was noted
      among participating clinics. The proportion of patients whose smoking status was
      identified and documented by any method increased from 50% to 87% (P < .01) at
      the 4 clinics with baseline data. By clinic, the increase varied from 6% to 60%.
      The sticker system was the method by which most patients' smoking status was
      documented (77%). There were no controls, so the influence of outside factors,
      including a regional smoking cessation campaign that coincided with this study,
      cannot be quantified. CONCLUSIONS: Managed care organizations may be an effective
      change agent for implementing the guidelines for tobacco use and dependence
      treatment.

PMID- 14572178
TI  - Barriers to mental health referral from pediatric primary care settings.
AB  - OBJECTIVE: To examine the frequency of barriers to mental health referral
      according to pediatric primary care physician (PCP) report and to identify
      factors related to perceptions of referral barriers for patients with managed
      care coverage. DESIGN AND METHODS: Data from a national sample of 319 PCPs were
      examined. Comparisons were made concerning the frequency of PCP-reported barriers
      to mental health referrals for patients with fee-for-service versus managed care
      coverage. The relationship between relevant factors (eg, practice structure,
      interdisciplinary office staff, availability of community mental health
      resources) and perceived barriers was examined for managed care coverage.
      RESULTS: Barriers to mental heath referrals were more commonly reported for those
      with managed care versus fee-for-service coverage for 11 of the 12 barriers
      assessed (P < .0001). For patients with managed care coverage a high availability
      of community mental health resources was associated with fewer perceived barriers
      among physicians (P < .0001). CONCLUSIONS: Our findings suggest that PCPs
      perceive barriers to mental health referrals as common challenges when addressing
      psychosocial concerns. Referral barriers were more commonly reported for patients
      with managed care coverage. Increasing the availability of community mental
      health resources was identified as an important variable in facilitating
      appropriate referrals.

PMID- 14572179
TI  - Impact of Maine's Medicaid drug formulary change on non-Medicaid markets:
      spillover effects of a restrictive drug formulary.
AB  - BACKGROUND: Market penetration of HMOs affect physician practice styles for non
      HMO patients. OBJECTIVE: To study the impact of a restrictive Medicaid drug
      formulary on prescribing patterns for other patients, ie, so-called spillover
      effects. DESIGN: A before-and-after, 3-state comparison study. EVENT: On January
      1, 2001, Maine's Medicaid program implemented a restrictive drug formulary for
      the proton pump inhibitor class, with pantoprazole as the only preferred drug.
      MAIN OUTCOME MEASURE: The Medicaid and non-Medicaid market shares of pantoprazole
      in Maine (vs New Hampshire and Vermont and among Maine physicians with different
      Medicaid share of practice. RESULTS: After 3 months, the market share of
      pantoprazole in Maine (vs 2 control states) increased 79% among Medicaid
      prescriptions (vs 1%-2%), 10% among cash prescriptions (vs 3%), and 7% among
      other third-party payer prescriptions (vs 1%). The market shares increased more
      among Maine physicians with a higher Medicaid share of practice (high vs middle
      vs low [market]: 16% vs 8% vs 5% [cash]; 11% vs 5% vs 4% [other third-party
      payers]). Linear regression results indicate that practicing medicine in Maine
      leads to a 72% increase in pantoprazole share among Medicaid prescriptions (P <
      .001). In addition, for each 10% Medicaid share of practice in Maine, the share
      of pantoprazole increases 1.8% among cash prescriptions (P = .01) and 1.4% among
      other third-party payer prescriptions (P < .001). CONCLUSIONS: Maine's Medicaid
      drug formulary generated spillover effects in cash and other third-party payer
      markets, with somewhat stronger effects in the cash market.

PMID- 14572180
TI  - Rates and symptoms of PTSD among cocaine-dependent patients.
AB  - OBJECTIVE: This study evaluated lifetime traumatic events and current
      posttraumatic stress disorder (PTSD) symptoms in a substance abuse sample.
      METHOD: Participants in the study consisted of 558 (75.1% male) cocaine-dependent
      individuals who completed self-report measures of trauma and PTSD symptoms prior
      to entry into treatment. RESULTS: Results showed a high number of lifetime
      traumatic events, even among those without PTSD. General disaster was the most
      prevalent. Current PTSD was found in 10.9% of the participants, with a
      significantly higher rate among women (21.6%) than among men (7.2%). For those
      with PTSD, the most prominent PTSD symptom cluster was arousal, and the most
      common symptoms were restricted affect, detachment and irritability. Participants
      with PTSD endorsed a large number of symptoms, almost double that needed to meet
      diagnostic criteria; however, neither number of traumas nor type of trauma was
      associated with their level of PTSD symptoms. Even among those not meeting PTSD
      criteria, subthreshold symptoms were found, with avoidance the most prominent
      cluster. Sociodemographic and recent cocaine use variables did not differentiate
      the PTSD from non-PTSD groups. CONCLUSIONS: PTSD is present in a sizeable
      percentage of cocaine-dependent treatment-seeking patients, particularly women.
      Clinicians might address arousal symptoms in particular, which were the most
      prominent symptom cluster, and which may be exacerbated by cocaine use. Even
      among those without PTSD, lifetime trauma is substantial and subthreshold PTSD
      symptoms are common. Vulnerability to PTSD needs further study, as
      sociodemographic and cocaine use variables did not distinguish between PTSD and
      non-PTSD groups.

PMID- 14572181
TI  - Patient depressive symptoms and therapist focus on emotional material: a new look
      at Project MATCH.
AB  - OBJECTIVE: Matching treatment modality to patient attribute generally did not
      improve outcomes in Project MATCH. Untested was whether actual therapist
      behaviors, irrespective of treatment modality, interacted with patient attributes
      to improve outcomes. The present study examined whether patient depressive
      symptoms interacted with therapist focus on painful emotional material to predict
      the effectiveness of alcohol treatment. Two competing theoretical approaches to
      treatment effectiveness were considered in light of the results. METHOD: A self
      report measure of pretreatment depressive symptoms was completed by 141
      participants from the Providence Clinical Research Unit of Project MATCH.
      Therapist focus on emotional material was then judged by independent observer
      ratings of videotaped treatment sessions. The interaction between these patient
      and therapy variables was tested as a predictor of percentage of days abstinent
      (PDA) and percentage of heavy drinking days (PHDD) during treatment and over the
      first year following treatment. RESULTS: The interaction between patient
      depressive symptoms and therapist emotion focus consistently predicted PDA and
      PHDD both during treatment and over the first year posttreatment. For patients
      with clinically elevated depressive symptoms, improved drinking outcomes occurred
      with a low therapist focus on painful emotional material. Conversely, depressed
      patients had worse drinking outcomes when the therapist had a high focus on
      emotional material. Therapist behavior did not affect drinking outcomes for
      patients with subclinical depressive symptoms. CONCLUSIONS: The interaction
      between depressive symptoms and therapist focus on emotional material was an
      important predictor of alcohol treatment effectiveness. The results appear to
      support a theory in which the reduction of patient arousal is a potential
      mediator of treatment effectiveness. The consistency and robustness of these
      findings suggest that matching actual therapist behaviors to patient attributes
      may improve drinking outcomes more than matching based solely on treatment
      modality.

PMID- 14572182
TI  - Psychiatric disorders among older adolescents treated in emergency departments on
      weekends: a comparison with a matched community sample.
AB  - OBJECTIVE: This study was undertaken to explore the characteristics of young
      patients treated in emergency departments (EDs) who follow through with an
      evaluation for psychiatric disorders as defined in the Diagnostic and Statistical
      Manual of Mental Disorders, Fourth Edition (DSM-IV) and to investigate
      differences in rates of psychiatric disorders between ED-treated adolescents and
      demographically similar adolescents recruited from the community. METHOD: Sixty
      three older adolescents (40 males) who were treated at two urban university
      hospital EDs were matched one-to-one on age, gender and race with 63 adolescents
      recruited from the community for participation in studies at an alcohol research
      center. Comprehensive psychiatric interviews were conducted with both groups.
      RESULTS: ED-treated adolescents were diagnosed with higher rates of current
      alcohol use disorders (AUDs), current drug use disorders and current major
      depression than were community controls. The ED sample had a particularly high
      rate of the DSM-IV "hazardous use" of alcohol symptom. ED-treated adolescents
      also had a higher rate of lifetime comorbid alcohol use disorders and drug use
      disorders, as well as a higher rate of lifetime comorbid alcohol use disorders
      and major depression, compared with the community controls. CONCLUSIONS:
      Adolescents who are treated in EDs should be routinely assessed for the presence
      of AUD, drug involvement and depressive disorders.

PMID- 14572183
TI  - Changes in alcohol consumption and in sexually transmitted disease incidence
      rates in the United States: 1983-1998.
AB  - OBJECTIVE: A substantial research literature has documented an association
      between alcohol consumption and risky sexual behavior at the level of the
      individual. We explored the association between changes in alcohol consumption
      and sexually transmitted disease (STD) incidence rates at the level of the 50
      U.S. states and the District of Columbia. METHOD: We used multivariate analyses
      to examine state-level changes in STD rates (gonorrhea and syphilis) and state
      level changes in alcohol consumption, controlling for changes in state-level
      characteristics (e.g.. poverty, age distribution of population) and for national
      trends in factors that affect STD rates. RESULTS: From 1983 to 1998, changes in
      alcohol consumption were significantly associated with changes in gonorrhea and
      syphilis rates. Each 1% increase in per capita alcohol consumption was associated
      with increases of about 0.4% to 0.7% in reported gonorrhea incidence rates and
      1.8% to 3.6% in reported syphilis incidence rates. CONCLUSIONS: The association
      between alcohol and risky sex, well documented at the level of the individual,
      might hold at the population level as well.

PMID- 14572184
TI  - Treatment nonseeking in alcohol users: a community-based study from North India.
AB  - OBJECTIVE: This study examined the reasons given for not seeking treatment by
      problem alcohol users who live close to a community outreach de-addiction center.
      METHOD: Consecutive households in the community were contacted, and inquiry
      identified 495 male family members who were using alcohol, 163 of whom reported
      use of alcohol in the previous year. Of these 163 subjects, the 79 who scored
      above the cut-off of > or = 8 on the Alcohol Use Disorders Identification Test
      were further evaluated using a semistructured interview schedule to determine
      their reasons for not seeking treatment. RESULTS: The majority (n = 40)
      considered alcohol use a "social" problem. Among the reasons for not seeking
      treatment, the two most commonly cited were "ashamed to admit problems" and
      "treatment does not help" in 26.5% (n = 21) and 22.8% (n = 18), respectively.
      CONCLUSIONS: The reasons for not seeking treatment for alcohol problems in this
      sample of Indian men resemble those cited in the literature. The data highlight
      the need for action to improve outreach to problem alcohol users.

PMID- 14572185
TI  - Personality differences between users of wine, beer and spirits in a community
      sample: the Winnipeg Health and Drinking Survey.
AB  - OBJECTIVE: To date there are many studies describing the protective and risk
      factors associated with alcohol consumption and cardiovascular health (the U- or
      J-shaped curve). These studies have only accounted for part of the effects. One
      hypothesis is that personality differences may account for some of the
      unexplained variance. It is also unclear if wine, beer and distilled spirits have
      equivalent effects on health. The purpose of this study is to describe the
      differences in personality among users of wine, beer and spirits. METHOD: Data
      were from a community sample of 1,257 men and women in Winnipeg, Manitoba,
      Canada, that was first enrolled in 1989-90. We examined and compared the
      demographic and personality characteristics of wine, beer and spirits drinkers in
      this sample. RESULTS: The groups differed significantly on the dimensions of
      extraversion, psychoticism and reducer-augmenter in univariate tests. In
      multivariate models, for the total sample and for females, predominant drinking
      of wine was associated with low scores on the Vando scale (augmenters). Higher
      consumption of beer among males was associated with higher levels of neuroticism.
      CONCLUSIONS: In these instances, personality does contribute to the
      characterization of groups.

PMID- 14572186
TI  - Alcohol-related injury in the ER: a cross-national meta-analysis from the
      Emergency Room Collaborative Alcohol Analysis Project (ERCAAP).
AB  - OBJECTIVE: To examine the impact of usual drinking patterns and related problems
      on the acute use of alcohol in injury. METHOD: The impact of quantity and
      frequency of drinking, alcohol problems and dependence symptoms on admission to
      the emergency room (ER) for an alcohol-related injury (based, separately, on a
      positive blood alcohol concentration [BAC] and self-reported drinking within 6
      hours prior to injury), compared with a nonalcohol related injury, was examined
      using meta-analysis, across 15 ER studies covering seven countries. RESULTS:
      Pooled effect size for consuming five or more drinks on an occasion at least
      monthly was significant but not homogeneous, with odds ratios (ORs) of 4.16 for
      BAC and 3.92 for self-report. Frequency of drinking among nonheavy drinkers was
      found to have the largest effect size (5.93 for BAC and 4.93 for self-report).
      Heavy drinking, controlling for frequency, was also significant (ORs of 2.08 for
      BAC and 1.86 for self-report), but effect size was homogeneous only for self
      report. Effect sizes for consequences of drinking and dependence symptoms were
      also significant and homogeneous, with ORs of 4.29 and 3.55, respectively, for
      BAC, and 3.84 and 3.94, respectively, for self-report. In meta-regression
      analysis, among contextual variables the level to which alcohol use is
      stigmatized in the culture was most consistently predictive of heavy-drinking
      effect size on an alcohol-related injury, with larger effect sizes found in those
      studies reporting a lower level of stigmatization. CONCLUSIONS: Whereas quantity
      and frequency of drinking were both found to be highly predictive of an alcohol
      related injury, sociocultural variables may affect observed associations of heavy
      drinking with an alcohol-related injury.

PMID- 14572187
TI  - Drunkenness among young people: a cross-national comparison.
AB  - OBJECTIVE: International studies show a rise in drunkenness among young people in
      recent years. In this study the number of drunkenness occasions among 15-year old
      students in 22 countries is reported. The cross-national association between
      drunkenness, on the one hand, and the frequency of alcohol intake and the
      preference for distilled spirits, on the other, is described. Variation between
      countries is examined on the basis of national characteristics, including
      national prevention policies. METHOD: Data on alcohol use were taken from the
      1998 World Health Organization (WHO) collaborative, cross-national survey on
      Health Behaviour of School-Aged Children. The multinational representative sample
      consisted of 10,951 male and 11,451 female (drinking) students. County
      characteristics were derived from the WHO Global Alcohol Database. Hierarchical
      Generalized Linear Model was used to analyze the effects of country
      characteristics on individual drunkenness. RESULTS: The lifetime prevalence of
      drunkenness was 57.1% for males and 50.4% for females. The number of drunkenness
      occasions showed a significant variation in the 22 countries. The correlation
      between drunkenness and preference for distilled spirits was positive in 21
      countries and strong (Spearman's p > 0.40) in some eastern countries. Geographic
      location turned out to be an important country-level association with drunkenness
      and its predictors. Southern European countries showed moderate associations,
      whereas strong associations were found in Scandinavia, the Baltic countries and
      Russia. CONCLUSIONS: Cultural differences in alcohol use exist, and frequency of
      alcohol intake and use of spirits influence drunkenness. Despite the potential
      influence of preventive policy measures on drunkenness, no preventive effect of
      the measures included in this study was found.

PMID- 14572188
TI  - Effects of acute administration of ethanol on the rat adrenal cortex.
AB  - OBJECTIVE: The purpose of this study was to investigate the effect of a single
      dose of ethanol on rat adrenal cortex and to determine whether the estrous cycle
      can influence this effect of ethanol. METHOD: Adult female Wistar rats showing
      proestrus or diestrus Day 1 (n = 12) were treated intraperitoneally with ethanol
      (4 g/kg body weight). Untreated (n = 15) and saline-injected (n = 14) rats were
      used as controls. The animals were sacrificed by decapitation 0.5 hour after
      ethanol administration. Stereological analysis was performed on paraffin sections
      of adrenal glands stained with AZAN, and the following parameters were
      determined: absolute volume of the zona glomerulosa, the zona fasciculata and the
      zona reticularis, numerical density, volume and the mean diameter of
      adrenocortical cells and of their nuclei, and diameter and length of capillaries.
      RESULTS: The diameter and volume of adrenocortical cells in the zona fasciculata
      and the zona reticularis were significantly increased by acute ethanol treatment
      at proestrus. In the same group of animals, a single dose of ethanol induced
      significant decrease in numerical density of adrenocortical cells and of their
      nuclei in all three zones. Increased length of capillaries of the zona
      fasciculata as well as enhanced level of serum corticosterone was found in
      ethanol-treated rats at both phases of the estrous cycle, proestrus and diestrus
      Day 1. CONCLUSIONS: The obtained results indicate that a single dose of ethanol
      activates adrenal cortex in female rats and that the effect is more pronounced on
      morphometric parameters at proestrus.

PMID- 14572190
TI  - Examining delinquency in adolescents differentially prenatally exposed to
      alcohol: the role of proximal and distal risk factors.
AB  - OBJECTIVE: An association has been reported between prenatal alcohol exposure and
      delinquent behavior in adolescents. Problems are believed to be particularly
      significant for those who were exposed prenatally but do not have full fetal
      alcohol syndrome (FAS). The goals of this study were (1) to examine the relation
      between a range oflevels of prenatal exposure and delinquent behavior in a
      community sample and (2) to examine the effect of other current risk factors, in
      addition to prenatal exposure, on delinquent behavior. METHOD: In this study, 250
      low income, predominantly black youths (mean age = 15.1 years) and their primary
      caregivers participated in an evaluation that included measures of delinquency,
      life stress, substance use, behavior problems, parenting practices, negative peer
      influence, caregiver substance use and the dysmorphia characteristic of FAS.
      Three groups were drawn from a sample initially seen at birth: Alcohol-exposed
      and dysmorphic (n = 39), alcohol-exposed, nondysmorphic (n = 77) and nonexposed
      controls (n = 48). A special education contrast group (n = 84) was recruited at
      adolescence to control for disability status. RESULTS: The exposure groups did
      not differ from controls on measures of variety and frequency of delinquent
      behavior; boys engaged in a wider range of delinquent acts than girls did.
      Regression analysis for the full sample revealed that higher adolescent life
      stress, higher self-reported drug use and lower parental supervision were
      significantly related to a wider range of delinquent acts. CONCLUSIONS: Other
      current influences should be considered in addition to prenatal alcohol exposure
      in interpreting the development of delinquency in alcohol-exposed adolescents.
      These results demonstrate the importance of examining risk factors and
      controlling effects of sociocultural influences and disability status when
      working with clinical samples.

PMID- 14572189
TI  - Alcohol's effects on perceptions of a potential date rape.
AB  - OBJECTIVE: The effects of alcohol consumption, alcohol expectancy set and self
      reported alcohol expectancies on college students' perceptions of a potential
      date rape situation were examined. It was hypothesized that the effects of
      alcohol consumption on perceptions of the likelihood of forced sex would be
      mediated by cognitive factors and perceived sexual arousal. METHOD: 90 female and
      90 male college students were randomly assigned to drink alcohol, a placebo
      beverage, or a nonalcoholic beverage. Participants read a story about a couple
      that had been drinking together at a party. The story ended with the woman saying
      "no" to sexual intercourse and the man exerting verbal pressure. RESULTS:
      Participants' alcohol consumption during the study, self-reported alcohol
      expectancies, attitudes about casual sex and usual drinking on dates had
      significant effects on their perceptions of the story. Participants' alcohol
      expectancy set and gender did not have significant effects on perceptions of the
      likelihood that the male character would force the female character to have sex.
      CONCLUSIONS: Intoxicated participants perceived the woman in the vignette as
      being more sexually arousedand the man in the vignette as behaving more
      appropriately, and both of these variables were negatively related to ratings of
      how likely it was that forced sex would occur. These findings highlight the
      importance of mediating cues in intoxicated decision making.

PMID- 14572191
TI  - Alcohol-induced impairment of behavioral control: effects on the alteration and
      suppression of prepotent responses.
AB  - OBJECTIVE: Alcohol use in humans is associated with aggression and other socially
      inappropriate behaviors. These adverse effects have been attributed to an acute
      impairment of behavioral control, and research findings indicate that inhibitory
      aspects of behavioral control might be particularly vulnerable to the effects of
      alcohol. The present study tested the degree to which alcohol-induced impairment
      of behavioral control is due to a specific impairment of inhibitory mechanisms or
      due to a general information processing deficit. METHOD: Forty subjects (29 men)
      performed a cued reaction time task before and after receiving 0.65 g/kg alcohol
      or a placebo. Subjects performed the task under conditions that differed in the
      type of response needed to maintain behavioral control: response-suppression and
      response-alteration. RESULTS: Alcohol impairment was observed when behavioral
      controlwas dependent on response-suppression, but no impairment was observed when
      control relied on response-alteration. CONCLUSIONS: The findings point to the
      susceptibility of inhibitory processes by showing that alcohol can be
      particularly detrimental to behavioral control in situations where prepotent
      responses must be completely suppressed. Evidence for alcohol-induced impairment
      of inhibitory functions could provide important clues about basic behavioral
      mechanisms by which alcohol disrupts such higher order cognitive processes as
      working memory, learning and decision making.

PMID- 14572192
TI  - Heavy drinking and alcohol policy enforcement in a statewide public college
      system.
AB  - OBJECTIVE: To assess the association between heavy drinking and alcohol policy
      enforcement following the institution of a new system-wide alcohol policy at
      Massachusetts public colleges and universities. METHOD: Students (N = 1,252: 59%
      women) at 11 study schools completed a questionnaire that assessed drinking
      behaviors and alcohol-associated problems. College deans and campus security
      officers completed questionnaires assessing policy implementation and
      enforcement. We compared heavy drinking rates among the 11 schools and measured
      the association between schools' heavy episodic drinking rates and enforcement
      index scores based on deans' and security officers' reports of policy
      enforcement. RESULTS: Rates of heavy episodic drinking varied widely among the 11
      schools (range: 36%-71%). The percentage of students reporting strict/very strict
      policy enforcement also varied widely (35%-90%). In this small sample of
      colleges, heavy drinking rates among students living on campus tended to be
      negatively associated with stricter alcohol policy enforcement reports by
      security officers (Pearson's r = -0.64. p < .05) and the association appeared to
      be linear. Heavy drinking was not associated with enforcement reports by deans
      (Pearson's r = 0.17, p = NS). CONCLUSIONS: Within this single state system,
      stricter enforcement by campus security officers of policies that limit underage
      drinking tends to be associated with lower rates of heavy drinking by students.

PMID- 14572193
TI  - Alcohol-related aggression and drinking at off-campus parties and bars: a
      national study of current drinkers in college.
AB  - OBJECTIVE: This study examines relationships between alcohol-related aggression
      and drinking at off-campus parties and bars. Other background variables include
      gender, year in school, residence and heavy drinking in college. METHOD: The
      study participants were respondents in the 1997 and 1999 Harvard School of Public
      Health College Alcohol Study, national surveys of students attending 119 4-year
      U.S. colleges. Based on responses from 8,426 students, 18-24 years of age, who
      were never married and who reported attendance at off-campus parties and bars in
      the past month, an exploratory factor analysis of the alcohol problem items was
      specified in a confirmatory factor analysis framework based on a two-factor
      solution (disruptive behavior and victims of altercations). In addition, the two
      factors were related to study variables. RESULT: Among students attending both
      off-campus parties and bars, level of drinking was related to higher levels of
      Factor 1 (disruptive behaviors) at off-campus parties and bars. Level of drinking
      was related to higher levels of Factor 2 (victims of altercations) at off-campus
      bars but not off-campus parties. Factor 1 was higher among men, freshmen and
      residents in coed dorms and lower among students living off-campus with parents.
      Factor 2 was higher among women, freshmen compared with seniors and residents of
      Greek houses and lower among students living off-campus residence with parents.
      CONCLUSIONS: Findings from this study highlight environmental factors in
      collegiate drinking practices and support targeted and diverse strategies for
      prevention activities.

PMID- 14572194
TI  - Drinking course in alcohol-dependent men from adolescence to midlife.
AB  - OBJECTIVE: Most studies of alcoholism course are based on clinical populations
      (characterized by severe and chronic alcohol-related problems) or community
      samples generally covering a short period of time. The current study assessed
      variations in drinking behaviors from adolescence to midlife in a community
      sample, describing age of "drinking firsts" (e.g., first alcoholic drink) as well
      as frequency and duration of periods of abstinence, alcohol dependence (AD) and
      nonproblem drinking. METHOD: Participants were 354 males with lifetime diagnoses
      of AD (mean age 50.35) from the Vietnam Era Twin Registry who were assessed
      regarding alcohol use, abuse and dependence histories (DSM-IV). Using a modified
      version of Skinner's Lifetime Drinking History, drinking history was reported in
      terms of distinct drinking periods (phases). RESULTS: Participants reported, on
      average, 4.18 phases, each lasting 8.22 years, and 12.78 years of AD. More than
      60% experienced increases in AD symptoms at least once in successive phases, but
      only a third of those increases were extreme. In contrast, extreme decreases in
      AD symptoms were reported by more than 50% of participants. Further, half
      indicated that they had transitioned from both fewer to greater and from greater
      to fewer AD symptoms during their drinking years; 8.2% reported no changes in AD
      symptoms. CONCLUSIONS: Results reflect a wide variation in drinking behaviors
      among AD men as well as frequent fluctuations in course within individuals'
      drinking histories. Findings do not support a universal developmental model of
      alcoholism; notably, they provide counterevidence to the disease model concept of
      alcoholism course as progressive and chronic.

PMID- 14572195
TI  - Effects of communities, neighborhoods and stores on retail pricing and promotion
      of beer.
AB  - OBJECTIVE: This study examines how communities, neighborhoods and stores
      influence retail pricing and promotion of beer. METHOD: In the year 2000, trained
      field staff conducted observations in 2,024 retail alcohol stores in 160
      communities throughout the contiguous United States. Based on a nationally
      representative sample of schools, we selected communities defined by the school's
      catchment area, or the vicinity from which the majority of students are drawn. We
      randomly selected off-sale alcohol retail establishments from a complete list of
      stores likely to sell tobacco or alcohol in the selected communities. Beer price
      and promotions are based on observations of Miller and Budweiser beer brands in
      the stores. Neighborhoods are defined by the store's census block. We used cross
      sectional, hierarchical regression models and mixed methods procedures to analyze
      data. RESULTS: Community, neighborhood and store characteristics were related to
      beer price; however, only community and store characteristics were predictive of
      beer promotions. CONCLUSIONS: Overall, the pricing and promotion of beer vary
      systematically by some characteristics of communities, neighborhoods and stores,
      but not significantly by the number of young people populating a neighborhood. In
      addition, pricing and promotion of Budweiser and Miller beers, in particular, do
      not appear to target racial minority populations. Because of the significant
      effect of store characteristics, public health agencies and advocates might focus
      prevention efforts on collaborations with liquor control agencies to reduce
      variations in pricing and promotion of beer, which ultimately encourage risky
      drinking behaviors. Further studies are needed to examine the effects of pricing
      and promotion on alcohol-related social problems.

PMID- 14572196
TI  - Validity of the CRAFFT in American-Indian and Alaska-Native adolescents:
      screening for drug and alcohol risk.
AB  - OBJECTIVE: Native-American adolescents are reported to be at high risk for drug
      and alcohol use and related negative consequences. A brief screening instrument
      that is culturally and developmentally appropriate can aid clinicians who work
      with Native youth in determining whether more extensive assessment of substance
      use is necessary. The CRAFFT has been shown to be a valid and reliable screen
      among general adolescent outpatient clinic samples. METHOD: Data were collected
      as part of the Journeys of the Circle project, a collaborative effort between the
      Seattle Indian Health Board (SIHB) and the University of Washington's Addictive
      Behaviors Research Center. Psychometric properties of the CRAFFT were examined in
      70 American-Indian and Alaska-Native youths ages 13 to 19 recruited from public
      schools and SIHBs outpatient clinics. RESULTS: The CRAFFT demonstrated good
      internal consistency (alpha = 0.81). A score of 2 or higher on the CRAFFT was
      found to be optimal for capturing youths with high alcohol-related problems
      (sensitivity, 0.95; specificity, 0.86), frequent alcohol use (sensitivity, 1.00;
      specificity, 0.72) and frequent marijuana use (sensitivity, 1.00; specificity,
      0.75). A cut-point of 3 was appropriate for identifying adolescents with frequent
      other drug use (sensitivity, 0.86; specificity, 0.76). CONCLUSIONS: The CRAFFT
      may be a valid instrument for identifying Native youths at risk for alcohol and
      other drug problems. This brief screen can be effective in helping providers
      determine the need for further assessment and treatment or prevention services
      for Native-American adolescents.

PMID- 14572198
TI  - Current and future applications of bone turnover markers.

PMID- 14572197
TI  - Factors affecting the validity of a Timeline Follow-Back interview.
AB  - OBJECTIVE: The Timeline Follow-Back (TLFB) interview is a calendar-prompted,
      retrospective measure of alcohol consumption. This report examines limitations of
      the TLFB's validity by examining change in reported consumption going back in
      time. METHOD: This report analyzes data from a case-control study. Cases (N =
      2,517; 56.9% men) were patients presenting for care of an acute injury to one of
      three emergency departments in Boone County, MO. Two control groups were
      recruited. Community controls (N = 1,856; 51.1% men) were recruited by random
      digit dialing and interviewed by telephone (response rate, 46.5%); medical
      patients (N = 2,103; 50.9% men) presenting for care of a noninjury illness were
      interviewed in person and, a few months later, by telephone (complete data
      obtained on 2,082). A 28-day TLFB interview was conducted with cases and
      community controls and an 8-day TLFB was done twice with medical controls.
      RESULTS: A linear regression analysis was done on each individual's drinking over
      the 28 or 8 days. Averaging participants' regression slopes, cases as a group
      showed a significant decay in self-reported consumption (0.011 drink per day for
      each day going back in time). Among community controls, the decay was
      significantly greater (0.018 drink per day). Analyzing only the 8 days prior to
      the day of interview, medical controls showed more evidence of bias than either
      cases or community controls. CONCLUSIONS: The smaller decay in cases' reporting
      is consistent with an effect of motivation (e.g., engagement in the interview
      process). Whether the interview is conducted in person (cases and first
      interviews with medical controls) or by telephone (community controls and second
      interviews with medical controls) may be relatively less important.

PMID- 14572199
TI  - A compilation of bone marker tests as found in the Internet.

PMID- 14572200
TI  - Two sensitive and rapid chromogenic assays of fondaparinux sodium (Arixtra) in
      human plasma and other biological matrices.
AB  - Fondaparinux is a synthetic selective inhibitor of factor Xa recently approved
      for thromboprophylaxis after major orthopedic surgery. Determination of its
      concentration gives valuable insight into specific pharmacokinetics or safety
      studies. The aim of the study was to develop direct, sensitive, precise and
      accurate assays of fondaparinux sodium in different biological matrices.
      Consistency with the recommended chromogenic assay for low molecular weight
      heparin required a similar method. However, recent data indicated some
      variability in the determination of anti-Xa level between commercial chromogenic
      assays. Consequently, we developed and validated two chromogenic methods (A and
      B) for assaying fondaparinux in plasma and other biological matrices. The assays
      are calibrated with fondaparinux, a pure chemical entity, and the result is
      expressed as amount (microg) of the fondaparinux calibrator. Results showed that
      precision was lower than 5.2% in plasma or plasma water and 13% in placental
      medium. The accuracy was lower than 7.6% in plasma or plasma water and 10.2% in
      placental medium. The lower limit of quantification in plasma was 0.042 microg/mL
      with automated Method A and 0.019 microg/mL with Method B. The assay was not
      affected by the source of the samples, the presence of blood cells, EDTA, citrate
      or repeated cycles of freezing and thawing. The two chromogenic assays calibrated
      with fondaparinux sodium reach the equivalence criteria for plasma samples and
      provide reliable and reproducible results.

PMID- 14572201
TI  - Immunoassay for soluble RANKL (receptor activator of NF-kappaB ligand) in serum.
AB  - This paper describes a method for the direct measurement of human sRANKL
      (receptor activator of NF-kappaB ligand), a cytokine of the tumor necrosis factor
      superfamily, which is a key player in bone metabolism. Its role in the regulation
      of osteogenic disorders such as osteoporosis, Paget's disease and rheumatoid
      arthritis is being extensively discussed in the literature at present. We
      developed a highly specific, simple and reliable ELISA which allows the direct
      measurement of uncomplexed sRANKL in human serum. Assay characteristics such as
      analytical precision, sensitivity, interfering factors, sample stability and
      dilution linearity are shown. Reference values from healthy volunteers (n=57)
      were found to be between 0 and 2.7 pmol/l (10th-90th percentile) with a mean
      serum value of 1.3 pmol/l (median 0.9 pmol/l).

PMID- 14572202
TI  - Determination of the components in erythrocytes using an automated analyzer.
AB  - Determination of the biochemical components in erythrocytes should provide unique
      pathophysiological information. We optimized a simple alcohol binding method for
      the selective removal of hemoglobins from hemolysates, and enabled simultaneous
      determination of several components in erythrocytes using commercially available
      assay kits in an automated analyzer. Venous blood was collected in a vacutainer
      containing lithium heparin. The washed cells were hemolyzed with distilled water,
      frozen, and then thawed. Nine volumes of the hemolysates were mixed with one
      volume of Tris-HCl buffer. One volume of n-butanol was then added to nine volumes
      of the buffered hemolysates. After vigorous mixing, the mixture of n-butanol and
      hemolysates was left to stand. The butanol-bound hemoglobins were precipitated by
      centrifugation, and the clear supernatant below the butanol layer was applied
      directly to an automated analyzer. Using sera, we determined the effects of the
      hemoglobin removal procedures on the chemical analytes. Sufficient recovery was
      noted in most analytes, except for several enzyme activities and lipids.
      Accordingly, we determined five components present in erythrocytes: creatine,
      potassium, magnesium, and aspartate aminotransferase as well as superoxide
      dismutase activities in healthy subjects. We suggest that our simple method is
      applicable to the simultaneous determination of erythrocyte components in routine
      laboratory tests.

PMID- 14572203
TI  - More on the reliability of the microparticle enzyme immunoassay (MEIA) for
      therapeutic tacrolimus monitoring.
AB  - Recently, the validity of determining tacrolimus concentrations in blood samples
      using Abbott's microparticle enzyme immunoassay (MEIA) has been seriously
      questioned. This communication presents the results obtained in our laboratory
      using the MEIA for 31 pooled blood samples from kidney and liver transplant
      patients (Tacrolimus International Proficiency Testing Scheme). A good
      correlation was found with regard to the average of the MEIA method (r=0.950)
      without reaching clinical significance for the difference between the means (9.54
      ng/ml vs 9.74 ng/ml), although the standard error of the estimate (Syx=0.66
      ng/ml) was clinically significant. With regard to the average values for HPLC
      methods, a lower correlation coefficient was found (r=0.819), with a difference
      between the means (9.54 ng/ml vs 8.91 ng/ml) slightly greater than the clinically
      acceptable value, and a clinically significant standard error of the estimate
      (Syx=1.22 ng/ml). In the case of the correlation between the average values for
      the MEIA and HPLC methods, a higher correlation coefficient was found (r=0.918),
      with a difference between the means (9.74 ng/ml vs 8.91 ng/ml) and a standard
      error of the estimate (Syx=0.75 ng/ml) being clinically significant. However,
      these differences were lesser than 15% of HPLC results in accordance with the
      American Association of Pharmaceutical Scientists acceptance criteria for
      analytical methods employed for quantification of drugs and their metabolites.

PMID- 14572204
TI  - Thrombin activatable fibrinolysis inhibitor (TAFI). A link between coagulation
      and fibrinolysis.

PMID- 14572205
TI  - Laboratory-based diagnosis of brucellosis--a review of the literature. Part I:
      Techniques for direct detection and identification of Brucella spp.
AB  - Brucellosis is a world-wide re-emerging zoonosis and the most frequent laboratory
      acquired bacterial infection, causing severe disease in humans with unspecific
      clinical signs affecting numerous organs. Contact with infected animals,
      ingestion of contaminated animal products and handling of Brucella isolates in
      laboratories are risk factors. Various other febrile illnesses, e.g. malaria,
      tuberculosis, typhoid fever and tularemia may present with the same symptoms.
      Therefore, clinical diagnosis is difficult to establish but effective therapy
      requires an early diagnosis. Vaccines for humans are still not commercially
      available. Blood culturing of Brucella is time-consuming and not reliable. Thus
      diagnosis is usually based on indirect serological tests, i.e. serum
      agglutination test, complement fixation or the Coombs test. However, these
      'conventional' serological tests lack sensitivity and specificity. Hence, a
      combination of various tests is mandatory for a definite diagnosis. Enzyme-linked
      immunosorbent assays can be used for screening and confirmation of brucellosis in
      one step. Molecular techniques like the polymerase chain reaction and restriction
      fragment length polymorphism are needed to differentiate species and strains
      within the genus Brucella. This review will summarize advantages and
      disadvantages of the techniques used in clinical laboratories for direct
      detection and identification of Brucella spp.

PMID- 14572206
TI  - DRG Watchdog highlights new financial dimensions of laboratory diagnostics.
AB  - As nebulous as the details of the German diagnosis-oriented case reimbursement
      rate (G-DRGs) might be, one thing is obvious: rapid and accurate diagnostics will
      be vital in future to the reimbursement of standard cases that reflect the actual
      outlay. The laboratory that up to now has always been categorized as a potential
      for savings, now becomes a source of revenue for hospitals. A study initiated by
      the VDGH provides evidence for this (Clinical Laboratory 2002, 48, 327).

PMID- 14572207
TI  - Renal diseases: modern expert systems improve diagnostics and therapy.
AB  - In the field of medicine, ever greater use is being made of modern data
      processing developments. The paramount targets are quality assurance and/or
      improvement of patient care. For the diagnosis of renal diseases and their
      courses of therapy, interesting knowledge-based expert systems are now available
      that make an important contribution to optimizing urine findings and detecting
      proteinuria while the course of disease is being controlled.

PMID- 14572208
TI  - Development of a selective broth medium for the detection of injured
      Campylobacter jejuni by capacitance monitoring.
AB  - The purpose of these studies was to develop a conductimetric method for the rapid
      detection of Campylobacter jejuni. Numerous basal medium components were analyzed
      to develop a growth-enhancing broth medium for detection of freeze-injured
      Campylobacter cells using a conductimetric system. The final medium was composed
      of a modified Campy-Line agar from which the agar and triphenyltetrazolium
      chloride were removed and the amino acid, L-arginine was added. Pure isolates of
      C. jejuni. (frozen and thawed to produce stressed cells) were utilized to test
      the detection methodology. Monitoring of significant changes in the capacitance
      signal was found suitable for detection of Campylobacter proliferation. Using
      stressed pure cultures, Campylobacter growth was repeatedly detected at very low
      inoculum levels (about one cell per well). There was a direct linear relationship
      between detection times (DTs) and the initial inoculum level. For example, using
      a single strain, the mean DT (n = 20) at the 10 CFU/ml inoculum level was 28.6 h,
      with 100% of the inoculated wells detecting. The mean DTs at the 100, 1,000, and
      10,000 CFU/ml inoculum levels were 24.9, 21.4, and 17.0 h, respectively. This
      study demonstrates that conductimetric methods can be utilized for the rapid
      detection of C. jejuni.

PMID- 14572209
TI  - Effect of inoculum size, relative humidity, storage temperature, and ripening
      stage on the attachment of Salmonella Montevideo to tomatoes and tomatillos.
AB  - The influence of inoculum populations and environmental factors on attachment of
      Salmonella Montevideo to the surface of tomatoes and tomatillos was evaluated. To
      study the effect of inoculum size, red, ripe tomatoes were spot-inoculated with
      bacterial suspensions (10(5) and 10(8) CFU/fruit) and stored at 22 degrees C
      under 100% relative humidity. The effects of temperature (12, 22, and 30 degrees
      C) and relative humidity (75, 85, and 97%) on attachment of the pathogen (10(7)
      CFU/fruit) to tomatoes (red and green) and ripe tomatillos were also evaluated.
      Inoculated fruits were stored for 90 min at all combinations of temperature and
      relative humidity, and after rinsing with water, the number of cells attached to
      the surface was determined. Salmonella Montevideo attached to the surface of
      tomatoes within 90 min. A direct correlation between the number of attached cells
      and the population in the inoculum was observed. The percentage of cells that
      attached immediately after inoculation was approximately 0.3% for the three test
      products. After storage for 90 min at various temperature and relative humidity
      conditions, the number of adhering cells ranged from 4.0 to 5.4 log CFU/fruit
      (1.2% of inoculum). Both the type of product and the temperature/relative
      humidity combination had a significant (P < 0.05) effect on attachment of
      Salmonella Montevideo to the surfaces of tomatoes and tomatillos. Scanning
      electron micrographs of the cuticles of inoculated washed tomatoes and tomatillos
      revealed typical skin cell patterns, and only a few randomly dispersed Salmonella
      Montevideo were observed. Deposition of Salmonella Montevideo on the surface of
      tomatoes and tomatillos could result in attachment and subsequent colonization
      under suitable conditions.

PMID- 14572210
TI  - Using a portable real-time PCR assay to detect Salmonella in raw milk.
AB  - The purpose of this study was to determine the efficacy of a portable real-time
      PCR system in detecting Salmonella spp. in raw milk. The 200 bulk milk samples
      chosen for this study constituted a subset of the samples for a larger study;
      this subset contained 24 samples that were culture positive for Salmonella and
      176 that were culture negative. Milk was both plated directly on selective agar
      and plated after enrichment in selective media. Presumptive Salmonella colonies
      were isolated by direct culturing of five samples, while Salmonella was isolated
      from the remaining 19 positive samples only after enrichment. Presumptive
      Salmonella isolates were serotyped, and isolates from 22 samples were confirmed
      to be Salmonella isolates. PCR assays of culture-positive milk prior to
      enrichment yielded no evidence of Salmonella. DNA extracts of bacterial pellets
      from the enriched samples were analyzed for Salmonella by real-time PCR with the
      Ruggedized Advanced Pathogen Identification Device (RAPID). Fifty-four samples
      from the enrichment pellets tested positive for Salmonella by real-time PCR. Two
      samples that tested positive for Salmonella by culture and serotyping tested
      Salmonella negative by real-time PCR. Serotyping identified isolates from these
      samples as Salmonella Montevideo. All DNA extracts of Salmonella Montevideo
      isolates tested positive for Salmonella by real-time PCR. Thirty-three samples
      tested negative by culture and positive by real-time PCR. These results indicate
      that the portable real-time PCR system appears to be a useful tool for detecting
      Salmonella in raw milk. Additionally, the combination of enrichment and real-time
      PCR techniques used in this study can yield results in 24 h, compared with the 48
      to 72 h required for traditional culture.

PMID- 14572211
TI  - Comparison of sampling methods for the detection of Salmonella on whole broiler
      carcasses purchased from retail outlets.
AB  - An experiment was conducted to compare the effectiveness levels of two methods in
      recovering Salmonella from the same carcass. One hundred fresh whole broiler
      chickens were purchased from retail outlets over a 5-week period (20 carcasses
      per week). After carcasses had been aseptically removed from the packages and
      giblets had been removed, the carcasses were placed in sterile bags containing
      400 ml of 1% buffered peptone water, the bags were shaken for 60 s, and a 30-ml
      aliquot was removed and incubated for 24 h at 37 degrees C (aliquot sample).
      Then, an additional 130 ml of 1% buffered peptone water was immediately added to
      the bag with the carcass (bringing the volume to 500 ml), the bag was reshaken,
      and the carcass and rinse were incubated for 24 h at 37 degrees C (whole-carcass
      enrichment sample). Following incubation, 0.5-ml samples for the two methods were
      placed into 10 ml of Rappaport-Vassiliadis broth and into 10 ml of tetrathionate
      (Hajna) broth and incubated at 42 degrees C for 24 h. Each broth was then
      streaked onto BG Sulfa agar and modified lysine iron agar and incubated for 24 h
      at 35 degrees C. Suspected Salmonella colonies were inoculated onto triple sugar
      iron and lysine iron agar slants and incubated at 35 degrees C for 24 h.
      Presumptive positive results were confirmed by Poly O and Poly H agglutination
      tests. Over the 5-week period, 13% of the aliquot samples tested positive for
      Salmonella, compared with 38% of the whole-carcass enrichment samples from the
      same carcasses. Recovery rates ranged from 0 of 20 samples to 4 of 20 samples for
      aliquot method and from 4 of 20 samples to 10 of 20 samples for the whole-carcass
      enrichment method over the 5-week period. These results indicate that when small
      numbers of Salmonella are expected, the sampling method has a major influence on
      the identification of Salmonella-positive carcasses.

PMID- 14572212
TI  - Thermal inactivation of Escherichia coli O157:H7 in cow manure compost.
AB  - Rates of inactivation of a five-strain mixture of green fluorescent protein
      labeled Escherichia coli O157:H7 in autoclaved and unautoclaved commercial cow
      manure compost with a moisture content of ca. 38% were determined at temperatures
      of 50, 55, 60, 65, and 70 degrees C. Trypticase soy agar with ampicillin was
      determined to be the best medium for the enumeration of heat-injured and
      uninjured cells of green fluorescent protein-labeled E. coli O157:H7. The results
      obtained in this study revealed that in autoclaved compost, E. coli O157:H7
      reductions of ca. 4 log CFU/g occurred within 8 h, 3 h, 15 min, 2 min, and < 1
      min at 50, 55, 60, 65, and 70 degrees C, respectively. At 65 and 70 degrees C,
      considerably less time was required to kill the pathogen in unautoclaved compost
      than in autoclaved compost. Decimal reduction times (D-values) for autoclaved
      compost at 50, 55, 60, 65, and 70 degrees C were 137, 50.3, 4.1, 1.8, and 0.93
      min, respectively, and D-values for unautoclaved compost at 50, 55, and 60
      degrees C were 135, 35.4, and 3.9 min, respectively. Considerable tailing was
      observed for inactivation curves, especially at 60, 65, and 70 degrees C. These
      results are useful for identifying composting conditions that will reduce the
      risk of the transmission of E. coli O157:H7 to foods produced in the presence of
      animal fecal waste.

PMID- 14572213
TI  - Escherichia coli O157:H7 prevalence in fecal samples of cattle from a
      southeastern beef cow-calf herd.
AB  - The proportion of fecal samples culture-positive for Escherichia coli O157:H7 was
      determined for samples collected from 296 beef cows on pasture in a single
      Florida herd in October, November, and December 2001. The overall proportion of
      samples that cultured positive was 0.03. The proportion of cows that were culture
      positive on at least one occasion was 0.091. No effect of pregnancy status or
      nutritional regimen on the proportion of culture-positive samples for E. coli
      O157:H7 was detected. We detected a breed effect on the shedding of E. coli O157,
      with Romosinuano cows having a lower (P < 0.01) proportion of samples culture
      positive than Angus or Brahman cows. This difference might have resulted from the
      presence of confounding variables; however, it also might represent evidence of
      breed-to-breed genetic variation in E. coli O157 shedding. Further research is
      warranted to evaluate breed as a possible risk factor for shedding of this
      important foodborne pathogen. Further substantiated findings could indicate that
      breed is a cow-calf-level critical control point of E. coli O157:H7.

PMID- 14572214
TI  - Enhanced inhibition of Escherichia coli O157:H7 by lysozyme and chelators.
AB  - This study examined the effects of three chelating agents (EDTA, disodium
      pyrophosphate [DSPP], and pentasodium tripolyphosphate [PSTPP]) on the inhibition
      of the growth of Escherichia coli O157:H7 by lysozyme. The objective of this
      study was to identify replacement chelators that exhibit synergistic properties
      similar to those of EDTA. The inhibitory effects of EDTA at 300 to 1,500
      microg/ml and of DSPP and PSTPP at 3,000 to 15,000 microg/ml in combination with
      lysozyme at 200 to 600 microg/ml for up to 48 h at pHs of 6.0, 7.0, and 8.0 on
      four strains of E. coli O157:H7 was studied with the use of a microbroth dilution
      assay. The addition of EDTA enhanced lysozyme's inhibitory effect on strains of
      E. coli O157:H7. EDTA at > or = 300 microg/ml combined with lysozyme at 200 to
      600 microg/ml was sufficient to inhibit the growth of the strains at pHs of 6.0
      and 8.0. At pH 7.0, lysozyme at 200 to 600 microg/ml and EDTA concentrations of >
      or = 1,000 microg/ml were effective in inhibiting three of the four strains. DSPP
      at pH 6.0 was inhibitory at > or = 10,000 microg/ml when combined with lysozyme
      at 200 to 300 microg/ml. In contrast, PSTPP increased the inhibitory activity of
      lysozyme more effectively at pH 8.0. Lysozyme at 200 to 600 microg/ml was
      effective against two strains of E. coli O157:H7 when used in conjunction with
      PSTPP at > or = 5,000 microg/ml. The remaining strains were inhibited by PSTPP at
      > or = 10,000 microg/ml. Our results indicate that inhibition occurred with each
      lysozyme-chelator combination, but the concentrations of phosphates required to
      increase the antimicrobial spectrum of lysozyme against E. coli O157:H7 were
      higher than the EDTA concentrations required to achieve the same effect.

PMID- 14572215
TI  - Interaction of Escherichia coli with growing salad spinach plants.
AB  - In this study, the interaction of a bioluminescence-labeled Escherichia coli
      strain with growing spinach plants was assessed. Through bioluminescence
      profiles, the direct visualization of E. coli growing around the roots of
      developing seedlings was accomplished. Subsequent in situ glucuronidase (GUS)
      staining of seedlings confirmed that E. coli had become internalized within root
      tissue and, to a limited extent, within hypocotyls. When inoculated seeds were
      sown in soil microcosms and cultivated for 42 days, E. coli was recovered from
      the external surfaces of spinach roots and leaves as well as from surface
      sterilized roots. When 20-day-old spinach seedlings (from uninoculated seeds)
      were transferred to soil inoculated with E. coli, the bacterium became
      established on the plant surface, but internalization into the inner root tissue
      was restricted. However, for seedlings transferred to a hydroponic system
      containing 10(2) or 10(3) CFU of E. coli per ml of the circulating nutrient
      solution, the bacterium was recovered from surface-sterilized roots, indicating
      that it had been internalized. Differences between E. coli interactions in the
      soil and those in the hydroponic system may be attributed to greater
      accessibility of the roots in the latter model. Alternatively, the presence of a
      competitive microflora in soil may have restricted root colonization by E. coli.
      The implications of this study's findings with regard to the microbiological
      safety of minimally processed vegetables are discussed.

PMID- 14572216
TI  - Development of a PCR assay for detection of Enterobacteriaceae in foods.
AB  - A broad-range PCR assay for the detection of bacteria belonging to the
      Enterobacteriaceae family was developed in this study. Primers targeting the
      bacterial 16S rRNA gene were newly designed and used in this PCR assay. To
      determine the specificity of the assay, 72 different bacterial species (of 49
      genera), 2 fungi, 3 animals, and 4 plants were tested. Results were positive for
      every tested Vibrioaceae or Enterobacteriaceae strain except Proteus mirabilis.
      For all other bacterial strains and eukaryotes tested, results were negative.
      Bacterial DNA for PCR was prepared by a simple procedure with the use of Chelex
      100 resin from culture after growth in brain heart infusion medium. To test this
      PCR assay for the monitoring of the Enterobacteriaceae family, either Escherichia
      coli or Salmonella Enteritidis was inoculated into various foods as an indicator.
      Prior to the PCR, the inoculation of 10 to 40 CFU of bacteria per g of food was
      followed by a 5-h enrichment culture step, and the PCR assay allowed the
      detection of bacterial cells. When actual examinations of the contamination of 15
      noodle foods with Enterobacteriaceae by this PCR assay were conducted, 33% (5 of
      15) of the samples tested positive. These results agreed with those of the
      Petrifilm Enterobacteriaceae Count Plate assay. Including the enrichment culture
      step, the entire PCR detection process can be completed within 7 h.

PMID- 14572217
TI  - Recovery of surface bacteria from and surface sanitization of cantaloupes.
AB  - Practical, effective methods that could be implemented in a food service
      establishment (restaurant or delicatessen) for the surface sanitization of
      cantaloupes were microbiologically evaluated. Cantaloupes (Cucumis melo L. var.
      reticulates) were immersed in an inoculum containing Salmonella enterica serovar
      Poona or Pantoea agglomerans at ca. 10(4) to 10(5) CFU/ml. An efficient method
      for the recovery of bacteria from the cantaloupe surface was developed and
      validated. The method consisted of washing the entire melon with Butterfield's
      buffer containing 1% Tween 80 in a plastic bag placed inside a plastic pail
      affixed to an orbital shaker. Levels of S. enterica Poona recovered by washing
      the entire melon were significantly higher than those recovered by the more
      common laboratory method of blending the rind. P. agglomerans can be used as a
      non-pathogenic proxy for S. enterica Poona. A three-compartment surface
      sanitization method consisting of washing with an antimicrobial soap solution,
      scrubbing with a brush in tap water, and immersion in 150 ppm of sodium
      hypochlorite reduced the initial level of recoverable viable bacteria by 99.8%.
      When examined separately, scrubbing with a vegetable brush in tap water, washing
      with soap, and dipping in chlorine were found to reduce the bacterial load by 70,
      80, and 90%, respectively.

PMID- 14572218
TI  - Antibacterial activities of phenolic benzaldehydes and benzoic acids against
      Campylobacter jejuni, Escherichia coli, Listeria monocytogenes, and Salmonella
      enterica.
AB  - We evaluated the bactericidal activities of 35 benzaldehydes, 34 benzoic acids,
      and 1 benzoic acid methyl ester against Campylobacter jejuni, Escherichia coli
      O157:H7, Listeria monocytogenes, and Salmonella enterica when these compounds
      were substituted on the benzene ring with 0, 1, 2, or 3 hydroxy (OH) and/or
      methoxy (OCH3) groups in a pH 7.0 buffer. Dose-response plots were used to
      determine the percentage of the sample that induced a 50% decrease in CFU after
      60 min (BA50). Of the 70 compounds tested, 24 were found to be active against all
      four pathogens, and additional 4, 10, and 12 were found to be active against
      three, two, and one of the pathogens, respectively. C. jejuni was approximately
      100 times as sensitive as the other three pathogens. The 10 compounds that were
      most active against the four pathogens (with average BA50 values ranging from
      0.026 to 0.166) and are candidates for studies of activity in foods or for
      disinfections were 2,4,6-trihydroxybenzaldehyde, 2,5-dihydroxybenzaldehyde, 2,3,4
      trihydroxybenzaldehyde, 2-hydroxy-5-methoxybenzaldehyde, 2,3
      dihydroxybenzaldehyde, 2-hydroxy-3-methoxybenzaldehyde, 4-hydroxy-2,6
      dimethoxybenzaldehyde, 2,5-dihydroxybenzaldehyde, 2,4-dihydroxybenzaldehyde. and
      2-hydroxybenzaldehyde. Comparison of the chemical structures of the test
      compounds and their activities revealed that (i) the aldehyde (CHO) group was
      more active than the carboxyl (COOH) group whether or not OH groups were present;
      (ii) compounds were most active with trisubstituted OH > disubstituted OH >
      monosubstituted OH; (iii) for disubstituted derivatives, 2-OH enhanced activities
      were exhibited by benzaldehyde but not by benzoic acid; (iv) compounds were more
      active with OH than with OCH3, irrespective of the position of substitution on
      the benzene ring; (v) compounds with mixed OH and OCH3 groups exhibited variable
      results, i.e., in some cases OCH3 groups enhanced activity and in other cases
      they did not; (vi) methoxybenzoic acids were largely inactive; and (vii) gallic
      acid was 20 times as active against S. enterica at pH 7.0 as it was at pH 3.7,
      suggesting that the ionization of its OH groups may enhance bactericidal
      activity.

PMID- 14572219
TI  - Bactericidal effects of konjac fluid on several food-poisoning bacteria.
AB  - In this study, the bactericidal effects of Japanese alkaline foods on food
      poisoning bacteria were evaluated. Konjac is an alkaline food soaked in
      calcinated calcium (the pH of konjac fluid ranges from 11.42 to 12.53). Konjac
      fluids completely inactivated Escherichia coli, enterohemorrhagic E. coli O157:H7
      and E. coil O26:H9, Salmonella Enteritidis, Vibrio parahemolyticus. and
      Staphylococcus aureus. The initial level of 6 log CFU/ml dramatically decreased
      after incubation with konjac fluid, and no viable gram-negative bacterium cells
      could be detected within 1 to 2 days and no viable S. aureus cells could be
      detected within 3 to 5 days. On the other hand, treatment with konjac fluid was
      also effective in reducing levels of spore-forming bacteria (Bacillus subtilis,
      Bacillus cereus, Clostridium perfringens, and Clostridium botulinum type E and
      type A). At least a 4-log reduction of spore-forming bacteria was obtained in
      konjac fluid within 7 to 14 days. Vegetative cells were more susceptible to
      konjac fluid than spores were. When the initial cell count was 6 log CFU/ml, a
      few surviving spores remained for 60 to 90 days, but no spores could be detected
      after 120 days. When the initial count of spore-forming bacteria was 3 to 4 log
      CFU/ml, the cells considered vegetative were completely inactivated within I to 3
      days. Repeated treatment with konjac fluid caused complete inactivation of spores
      in less than 1 to 3 days. Our studies indicate that konjac fluid, which has a
      long history of use in food, will control food-poisoning bacterial contamination
      during the production or preservation of konjac and other foods and has a
      preventive effect on bacteria that can cause severe disease at uniquely low
      levels.

PMID- 14572220
TI  - Prevalence of Listeria monocytogenes in, and microbiological and sensory quality
      of, rainbow trout, whitefish, and vendace roes from Finnish retail markets.
AB  - The prevalence of Listeria monocytogenes in retail roe, as well as the
      microbiological and sensory qualities of the roe, were studied for three fish
      species under three different storage conditions. A total of 147 Finnish rainbow
      trout (Oncorhynchus mykiss), whitefish (Coregonus lavaretus), vendace (Coregonus
      albula), and burbot (Lota lota) roe samples were bought fresh, frozen, or frozen
      thawed from Finnish retail markets. The overall prevalence of L. monocytogenes
      was 5%; however, the prevalence of the pathogen in fresh roe was 18%. Fresh
      bought roe tested positive for Listeria spp. and for L. monocytogenes,
      respectively, 5 and 20 times as often as did frozen and frozen-thawed roe
      products combined. The microbiological quality (analyzed as total aerobic
      heterotrophic bacteria and coliform bacteria) of 78% of the roe samples was
      unacceptable. Frozen roe samples were found to have the best microbiological
      quality. According to the results of a sensory evaluation, at least one sensory
      attribute (appearance, odor freshness, texture, and freshness of taste) was
      unacceptable for 29% of the roe samples studied. The sensory quality of roe
      samples bought fresh was better than that of roe samples bought frozen or frozen
      thawed. From the results of this study, it is concluded that both the
      microbiological and the sensory qualities of roe at the retail level need to be
      improved.

PMID- 14572221
TI  - Survival of Listeria monocytogenes in a simulated recirculating brine chiller
      system.
AB  - Contamination by Listeria monocytogenes of processed meats after cooking presents
      a significant food safety risk. The purpose of this study was to determine the
      survival of L. monocytogenes in a simulated recirculating brine chiller system
      using pH values of 5, 6, and 7 with free chlorine concentrations of 0, 3, 5, and
      10 ppm in 20% salt brine at -12 degrees C. At pH values of 5, 6, and 7 with
      chlorine concentrations of 2 and 3 ppm, using 10(8) CFU in a test tube system, an
      immediate drop of 0.28 log CFU/ml with no significance between treatments (P >
      0.05), followed by a steady survival phase with a slope close to 0, was observed.
      In brine at a pH of 5 with 5 and 10 ppm of chlorine, an initial drop of 0.8 log
      CFU/ml was observed, which was followed by a steady survival phase with a
      destruction slope close to zero. At an inoculation concentration of 10(2) CFU in
      a test tube system (pH values of 5 and 7 with 0 and 10 ppm of chlorine), the
      average initial drop for all treatments was 0.1 log CFU/ml, which was followed by
      a steady survival phase. In a recirculating system, very few cells were destroyed
      during the brine chilling process, but only low numbers of L. monocytogenes were
      recovered from the brine and uninoculated hot dogs. Although little destruction
      of L. monocytogenes was noted, the dilution effect observed during the study
      indicates that environmental contamination of a brine chiller system poses little
      danger of postcooking contamination for processed meats if the system is
      regularly cleaned and sanitized.

PMID- 14572222
TI  - Hemolytic and nonhemolytic vancomycin-resistant Enterococcus faecalis isolated
      from beef imported to Malaysia.
AB  - Twenty-two strains of vancomycin-resistant Enterococcus faecalis were isolated
      from 9 (6%) of 150 samples of frozen beef and beef products imported to Malaysia.
      The isolates were obtained from eight samples of beef and one sample of minced
      beef patty. No E. faecalis was isolated from frankfurters. Twelve of the 22
      isolates (54.5%) were beta-hemolytic, and all isolates harbored the vanA gene.
      All vancomycin-resistant isolates were also resistant to streptomycin,
      erythromycin, kanamycin, bacitracin, ceftazimide, gentamycin, tetracycline,
      nalidixic acid, and teicoplanin; 95.4% were resistant to
      trimethoprimsulfamethoxazole; 68.8% were resistant to chloramphenicol; and 41%
      were resistant to ampicillin and penicillin. Small plasmids ranging in size from
      1.5 to 5.8 kb were detected in 8 (36.4%) of 22 strains. The 22 isolates were
      classified into 20 random amplified polymorphic DNA types. Isolates were divided
      into two groups, each containing subclusters, that may reflect their clonal
      lineages. It is concluded that several clones of vancomycin-resistant E. faecalis
      are represented in the isolates obtained from beef imported to Malaysia.

PMID- 14572224
TI  - Infectivity of Trichinella nativa in traditional northern (country) foods
      prepared with meat from experimentally infected seals.
AB  - The infectivity of Trichinella nativa larvae in three traditional northern
      (country) foods was assessed. Foods were prepared with meat from seals
      experimentally infected with Trichinella nativa and evaluated over a 317-day
      period during which this food was fed directly to cats while mice were orally
      inoculated with larvae recovered following the digestion of the food in a
      solution containing 1% pepsin and 1% HCl at 37 degrees C. Foods examined were
      igunaq (meat and blubber placed in a seal skin bag and allowed to ferment), nikku
      (air-dried meat), and sausage (meat, fillers, salt, and spices). Sausage was
      examined both in a raw state and after partial cooking. Infective T. nativa
      larvae survived in igunaq, nikku, raw frozen sausage, and poorly cooked sausage
      for at least 5 months under controlled laboratory conditions. Core temperatures
      of partially cooked sausage never exceeded 50 degrees C. Caution should be
      exercised in using these data to establish guidelines for the consumption of raw
      products, since the survival of infective larvae could be unpredictably extended
      under field conditions. These data indicate significant food safety risks
      associated with igunaq, nikku, and sausage prepared with Trichinella-infected
      meat and provide information for use in risk management and in directing future
      research.

PMID- 14572223
TI  - Detection of staphylococcal enterotoxin B in spiked food samples.
AB  - Contamination of food with infectious agents, intentional or not, is a global
      concern with far-reaching economic and social impact. Staphylococcal enterotoxins
      are a major cause of food poisoning, but most methods for the identification of
      these agents in food require extensive pretreatment or concentration of the
      sample prior to analysis. The array biosensor was developed as a portable device
      for the simultaneous analysis of multiple complex samples for multiple targets
      with minimal sample preparation. In this study, we use an array biosensor to
      expand and improve on a staphylococcal enterotoxin B (SEB) assay with the
      ultimate intent of incorporating testing for SEB into a battery of sensitive and
      convenient assays for food safety validation. In addition to buffer studies, six
      different types of food samples, including beverages, homogenates of fruit and
      meat, and carcass washings, were spiked with SEB, incubated for at least 2 h to
      permit antigen sequestration, and assayed. For all samples, there were
      differences in fluorescence intensity, but 0.5 ng of SEB per ml could be detected
      in <20 min with little if any pretreatment and no sample preconcentration.

PMID- 14572225
TI  - Modified atmosphere packaging for prevention of mold spoilage of bakery products
      with different pH and water activity levels.
AB  - A sponge cake analog was used to study the influence of pH, water activity (aw),
      and carbon dioxide (CO2) levels on the growth of seven fungal species commonly
      causing bakery product spoilage (Eurotium amstelodami, Eurotium herbariorum,
      Eurotium repens, Eurotium rubrum, Aspergillus niger, Aspergillus flavus, and
      Penicillium corylophilum). A full factorial design was used. Water activity, CO2,
      and their interaction were the main factors significantly affecting fungal
      growth. Water activity at levels of 0.80 to 0.90 had a significant influence on
      fungal growth and determined the concentration of CO2 needed to prevent cake
      analog spoilage. At an aw level of 0.85, lag phases increased twofold when the
      level of CO2 in the headspace increased from 0 to 70%. In general, no fungal
      growth was observed for up to 28 days of incubation at 25 degrees C when samples
      were packaged with 100% CO2, regardless of the aw level. Partial least squares
      projection to latent structures regression was used to build a polynomial model
      to predict sponge cake shelf life on the basis of the lag phases of all seven
      species tested. The model developed explained quite well (R2 = 79%) the growth of
      almost all species, which responded similarly to changes in tested factors. The
      results of this study emphasize the importance of combining several hurdles, such
      as modified atmosphere packaging, aw, and pH, that have synergistic or additive
      effects on the inhibition of mold growth.

PMID- 14572227
TI  - Manual sorting to eliminate aflatoxin from peanuts.
AB  - A manual sorting procedure was developed to eliminate aflatoxin contamination
      from peanuts. The efficiency of the sorting process in eliminating aflatoxin
      contaminated kernels from lots of raw peanuts was verified. The blanching of 20
      kg of peanuts at 140 degrees C for 25 min in preheated roasters facilitated the
      manual sorting of aflatoxin-contaminated kernels after deskinning. The manual
      sorting of raw materials with initially high aflatoxin contents (300 ppb)
      resulted in aflatoxin-free peanuts (i.e., peanuts in which no aflatoxin was
      detected). Verification procedures showed that the sorted sound peanuts contained
      no aflatoxin or contained low levels (<15 ppb) of aflatoxin. The results obtained
      confirmed that the sorting process was effective in separating contaminated
      peanuts whether or nor contamination was extensive. At the commercial level, when
      roasters were not preheated, the dry blanching of 50 kg of peanuts for 45 to 55
      min facilitated the proper deskinning and subsequent manual sorting of aflatoxin
      contaminated peanut kernels from sound kernels.

PMID- 14572226
TI  - Effects of muffin processing on fumonisins from 14C-labeled toxins produced in
      cultured corn kernels.
AB  - The persistence of fumonisins during cooking is known to be affected by several
      factors, including thermal degradation and the presence of various ingredients in
      corn-based food recipes that can react with the toxin. A method for the
      production of corn kernels containing 14C-fumonisins was developed. The corn
      kernels were colonized by Fusarium verticillioides MRC 826 and supplemented with
      1,2-14C-sodium acetate. The specific activity of 14C-FB1 produced made the study
      of its fate in cornmeal muffins possible. The double-extraction acetonitrile
      water-methanol/immunoaffinity column/o-phthaldialdehyde high-performance liquid
      chromatography (HPLC) method was used to determine FB1 levels in cornmeal
      muffins. Reductions in FB1 levels in muffins spiked with 14C-labeled and
      unlabeled FB1 (43 and 48%, respectively) were similar, indicating that the
      extraction method was efficient and consistent with previous reports. However,
      with the labeled corn kernel material, recovery levels based on the 14C counts
      for the eluate from an immunoaffinity column were much higher (90%). This finding
      indicates that some fumonisin-related compounds other than FB1 that were present
      in the cornmeal were recognized by the antibodies but not by the HPLC method.

PMID- 14572228
TI  - Aflatoxin M1 in pasteurized and ultrapasteurized milk with different fat content
      in Mexico.
AB  - High per capita milk consumption in Mexico indicated a strong need for
      documentation of aflatoxin M1 (AFM1) levels in milk. A survey of 580, 2-liter
      samples (n = 290), was conducted to quantify AFM1 using high-performance liquid
      chromatography, considering two maximum tolerance levels (0.05 and 0.5
      microg/liter). We relate aflatoxin levels in the seven most consumed brands from
      different regions, with two processes (pasteurized and ultrapasteurized),
      different expiration dates, and different fat content: whole fat (28, 30, and 33
      g), half-skimmed (10, 16, and 20 g), light (1, 2, and 4 g), and with vegetable
      oil. Pasteurization and ultrapasteurization did not diminish AFM1 contamination
      present at levels of 0 to 8.35 microg/liter in 40% of the milk samples at
      concentrations > or = 0.05 microg/liter and in 10% of the samples at > or = 0.5
      microg/liter. Statistically significant relationships were AFM1 contamination
      with brand (P = 0.002 at the > or = 0.05 microg/liter level and P = 0.034 at the
      > or = 0.5 microg/ liter level) and higher AFM1 levels with mild or warm seasons
      of the year (P = 0.0003). Samples with greater fat content had slightly more
      probability (P = 0.067) of being contaminated by AFM1 at the > or = 0.5
      microg/liter level. The milk with the lowest contamination of AFM1 was a brand
      imported as powder and rehydrated in Mexico.

PMID- 14572229
TI  - Consumer food-handling behaviors associated with prevention of 13 foodborne
      illnesses.
AB  - To be effective in reducing the incidence of foodborne illness, consumers and
      food safety educators need information about behaviors that will decrease
      exposure to foodborne pathogens. A four-round Delphi technique was used to survey
      nationally recognized experts in food microbiology, epidemiology, food safety
      education, and food safety policy with the aim of identifying and ranking food
      handling and consumption behaviors associated with 13 major foodborne pathogens.
      The food safety experts ranked behaviors related to keeping foods at safe
      temperatures as of primary importance in preventing illness caused by Bacillus
      cereus and Clostridium perfringens and of secondary importance in preventing
      illness caused by Staphylococcus aureus. The use of a thermometer to cook foods
      adequately was ranked as of primary importance for the prevention of illness
      caused by Campylobacter jejuni, Salmonella species, Escherichia coli O157:H7,
      Toxoplasma gondii, and Yersinia enterocolitica, with the avoidance of cross
      contamination being ranked as of secondary importance for most of these
      pathogens. Hand washing was the top-ranked behavior for the prevention of
      shigellosis. The avoidance of certain foods that are likely to be contaminated
      was the top-ranked behavior for the prevention of illnesses caused by Listeria
      monocytogenes, Noroviruses, and Vibrio species. The expert panel's ranking of
      behaviors for the reduction of the risk of illness caused by major foodborne
      pathogens can enable consumers to make informed choices about food consumption
      and handling behaviors and can guide food safety educators in prioritizing their
      educational efforts.

PMID- 14572231
TI  - Efficacy of enrichment broths in the recovery of freeze-injured Escherichia coli
      O157:H7 in inoculated ground beef by PCR.
AB  - Escherichia coli O157:H7 strains ATCC 35150 and ATCC 43894 and five pooled
      isolates from beef and pork freeze injured at -25 degrees C in beef infusion were
      used to inoculate ground beef. Samples (25 g each) were added to 225 ml of
      buffered peptone water with vancomycin, cefsulodin, and cefixime (BPW-VCC), 225
      ml of modified EC broth plus novobiocin (mEC+n), and 225 ml of R&F enrichment
      broth (R&F-EB) and aerobically incubated at 41 to 42 degrees C. After 6, 7, 8,
      and 24 h of incubation, levels of E. coli O157:H7 recovered from each broth by a
      PCR assay with the BAX automated system as well as by conventional enrichment
      with the use of nonaerated mEC+n incubated at 35 degrees C for 24 h were compared
      with levels recovered by cultural isolation with immunomagnetic separation and
      plating on BCM E. coli O157:H7 chromogenic agar. For ground beef inoculated with
      a mean of 4.23 +/- 1.00 total cells (74% freeze injured) per 25 g, after 6 h the
      PCR assay identified 72.7, 57.6, and 66% of the samples for R&F-EB, BPW-VCC, and
      mEC+n, respectively, as presumptive positive, whereas the recovery rates after 7
      and 8 h exceeded 90%, with the rate for R&F-EB being 100%. For ground beef
      inoculated with a mean of 1.50 +/- 0.56 total cells (80% freeze injured) per 25
      g, after 6 h the PCR assay identified 47.6, 19.1, and 9.5% of the samples for R&F
      EB, BPW-VCC, and mEC+n, respectively, as presumptive positive. These values
      increased to 81.0, 61.9, and 52.4% after 7 h and to 95.2, 61.9, and 71.4% after 8
      h. After 24 h, only 55 to 60% of the samples at both inoculum levels tested
      positive by PCR with conventional enrichment and incubation, whereas >95% of the
      samples tested positive with R&F-EB aerated at 41 to 42 degrees C. Culture
      results for R&F-EB and mEC+n after 7 and 8 h of incubation were closely
      correlated with presumptive positive PCR results.

PMID- 14572230
TI  - Comparison of Monte Carlo and fuzzy math simulation methods for quantitative
      microbial risk assessment.
AB  - The objective of food safety risk assessment is to quantify levels of risk for
      consumers as well as to design improved processing, distribution, and preparation
      systems that reduce exposure to acceptable limits. Monte Carlo simulation tools
      have been used to deal with the inherent variability in food systems, but these
      tools require substantial data for estimates of probability distributions. The
      objective of this study was to evaluate the use of fuzzy values to represent
      uncertainty. Fuzzy mathematics and Monte Carlo simulations were compared to
      analyze the propagation of uncertainty through a number of sequential
      calculations in two different applications: estimation of biological impacts and
      economic cost in a general framework and survival of Campylobacter jejuni in a
      sequence of five poultry processing operations. Estimates of the proportion of a
      population requiring hospitalization were comparable, but using fuzzy values and
      interval arithmetic resulted in more conservative estimates of mortality and
      cost, in terms of the intervals of possible values and mean values, compared to
      Monte Carlo calculations. In the second application, the two approaches predicted
      the same reduction in mean concentration (-4 log CFU/ ml of rinse), but the
      limits of the final concentration distribution were wider for the fuzzy estimate
      (-3.3 to 5.6 log CFU/ml of rinse) compared to the probability estimate (-2.2 to
      4.3 log CFU/ml of rinse). Interval arithmetic with fuzzy values considered all
      possible combinations in calculations and maximum membership grade for each
      possible result. Consequently, fuzzy results fully included distributions
      estimated by Monte Carlo simulations but extended to broader limits. When limited
      data defines probability distributions for all inputs, fuzzy mathematics is a
      more conservative approach for risk assessment than Monte Carlo simulations.

PMID- 14572232
TI  - Effect of freezing, irradiation, and frozen storage on survival of Salmonella in
      concentrated orange juice.
AB  - Six strains of Salmonella (Anatum F4317, Dublin 15480, Enteritidis 13076,
      Enteritidis WY15159, Stanley H0588, and Typhimurium 14028) were individually
      inoculated into orange juice concentrate (OJC) and frozen to -20 degrees C. The
      frozen samples were treated with 0 (nonirradiated), 0.5, 1.0, or 2.0 kGy of gamma
      radiation and held frozen for 1 h, and the surviving bacterial population was
      assessed. The strains showed significant variability in their response to
      freezing and to freezing in combination with irradiation. The response was dose
      dependent. Relative to the nonfrozen, nonirradiated control, the reduction
      following the highest dose (2.0 kGy) ranged from 1.29 log CFU/ml (Salmonella
      Typhimurium) to 2.17 log CFU/ml (Salmonella Stanley). Samples of OJC inoculated
      with Salmonella Enteritidis WY15159 and irradiated were stored at -20 degrees C
      for 1, 2, 7, or 14 days, and the surviving population was determined. Relative to
      the nonfrozen, nonirradiated control, after 14 days, the population was reduced
      by 1.2 log CFU/ml in the nonirradiated samples and by 3.3 log CFU/ml following
      treatment with 2.0 kGy. The combination of frozen storage plus irradiation
      resulted in greater overall reductions than either process alone.

PMID- 14572233
TI  - Validation of the USDA/ARS package rinse method for recovery of Listeria
      monocytogenes from naturally contaminated, commercially prepared frankfurters.
AB  - The utility of the U.S. Department of Agriculture/Agricultural Research Service
      (USDA/ARS) package rinse method for recovering Listeria monocytogenes from the
      surface of contaminated foods was validated in comparison to the standard
      USDA/Food Safety and Inspection Service (FSIS) product composite enrichment
      method and two other methods using frankfurters from a lot with a known package
      prevalence rate of approximately 16% for this pathogen. One hundred packages from
      this batch of naturally contaminated, commercially prepared frankfurters were
      examined as follows: (i) the package exudative fluid was removed and tested using
      the standard USDA/FSIS product composite enrichment method; (ii) approximately 5
      to 7 portions of frankfurters were removed to obtain a 25-g composite of meat
      that was then processed using the standard USDA/FSIS product composite enrichment
      method: (iii) 50 ml of 0.1% peptone water was added to each package, and the
      USDA/ARS package rinse method was performed on the remaining contents; and (iv)
      after removing the rinse fluid, the solid contents remaining in each package were
      directly enriched using the USDA/FSIS product composite enrichment method. These
      four methods identified that 7, 6, 15, and 9 of the 100 packages tested positive
      for the pathogen, respectively. Although no single approach yielded a positive
      result for every package that tested positive for L. monocytogenes by any one of
      the four sampling strategies, the USDA/ARS package rinse method was appreciably
      (P < 0.05) better than either the package exudate enrichment method or the
      standard USDA/FSIS product composite enrichment method at recovering the
      bacterium. These findings validate the sensitivity and ease of use of the
      USDA/ARS package rinse method using naturally contaminated frankfurters and argue
      strongly for its adoption for routine screening of ready-to-eat products that are
      prone to surface contamination with undesirable microbes such as L.
      monocytogenes.

PMID- 14572234
TI  - High hydrostatic pressure treatment of finfish to inactivate Anisakis simplex.
AB  - High hydrostatic pressure has been demonstrated to be a useful technique for
      treating food to reduce the number of pathogenic organisms and to extend shelf
      life. Most research in this area has focused on bacteria. However, a concern in
      the sashimi (raw fish) industry is that nematode worms such as Anisakis simplex
      occur naturally in cold-water marine fish. The objectives of this research were
      to perform a pilot study to determine the effect of high hydrostatic pressure on
      the viability of Anisakis simplex larvae, commonly found in king salmon and
      arrowtooth flounder, and to evaluate the effects of high hydrostatic pressure on
      the color and texture of the fish fillets. Pieces of fish (ca. 100 g per bag)
      containing 13 to 118 larvae were exposed to pressures of up to 80,000 lb/in2 (552
      MPa) for up to 180 s. The times and pressures required to kill 100% of the larvae
      were as follows: 30 to 60 s at 60,000 lb/in2 (414 MPa), 90 to 180 s at 40,000
      lb/in2 (276 MPa), and 180 s at 30,000 lb/in2 (207 MPa). For all salmon treatments
      that killed 100% of the larvae, a significant increase in the whiteness of the
      flesh was observed. Although high hydrostatic pressure was effective in killing
      A. simplex larvae in raw fish fillets, its significant effect on the color and
      overall appearance of the fillet may limit its application to the processing of
      fish for raw-fish markets.

PMID- 14572235
TI  - Construction and preliminary evaluation of an Aspergillus flavus reporter gene
      construct as a potential tool for screening aflatoxin resistance.
AB  - Effective preharvest strategies to eliminate aflatoxin accumulation in crops are
      not presently available. The molecular biology of aflatoxin biosynthesis has been
      extensively studied, and genetic and molecular tools such as reporter gene
      systems for the measurement of fungal growth have been developed. A reporter
      construct containing the Aspergillus flavus beta-tubulin gene promoter fused to
      Escherichia coli beta-glucuronidase (GUS) has been shown to be a reliable tool
      for the indirect measurement of fungal growth in maize kernels. Since cost-saving
      alternative methods for the direct measurement of aflatoxin levels are needed to
      facilitate more widespread field and laboratory screening of maize lines, a new
      reporter gene construct involving the promoter region of the omtA gene of the
      aflatoxin biosynthetic pathway was constructed and tested. Expression of GUS
      activity by this construct (omtA::GUS) was correlated with aflatoxin accumulation
      in culture. In the fungal transformant GAP26-1, which harbors this construct,
      aflatoxin production and GUS expression on sucrose-containing medium showed the
      same temporal pattern of toxin induction. Furthermore, GUS expression by GAP26-1
      was shown to be associated with aflatoxin accumulation in maize kernels
      inoculated with this strain. Our results suggest that this and other reporter
      gene pathway promoter constructs may provide superior alternatives to direct
      aflatoxin quantification with respect to time, labor, and materials for the
      screening of maize lines for resistance to aflatoxin accumulation.

PMID- 14572236
TI  - Presence of undeclared peanut protein in chocolate bars imported from Europe.
AB  - Peanut allergens are both stable and potent and are capable of inducing
      anaphylactic reactions at low concentrations. Consequently, the consumption of
      peanuts remains the most common cause of food-induced anaphylactic death. Since
      accidental exposure to peanuts is a common cause of potentially fatal anaphylaxis
      in peanut-allergic individuals, we tested for the presence of peanut protein in
      chocolate bars produced in Europe and North America that did not list peanuts as
      an ingredient. Ninety-two chocolate bars, of which 32 were manufactured in North
      America and 60 were imported from Europe, were tested by the Veratox assay. None
      of the 32 North American chocolate products, including 19 with precautionary
      labeling, contained detectable peanut protein. In contrast, 30.8% of products
      from western Europe without precautionary labeling contained detectable levels of
      peanut protein. Sixty-two percent of products from eastern Europe without
      precautionary labeling contained detectable peanut protein at levels of up to 245
      ppm. The absence of precautionary labeling and the absence of the declaration of
      "peanut" as an ingredient in chocolate bars made in eastern and central Europe
      were not found to guarantee that these products were actually free of
      contaminating peanut protein. In contrast, North American manufacturers have
      attained a consistent level of safety and reliability for peanut-allergic
      consumers.

PMID- 14572237
TI  - Methods for rapid separation and concentration of bacteria in food that bypass
      time-consuming cultural enrichment.
AB  - The rapid detection of pathogenic organisms that cause foodborne illnesses is
      needed to insure food safety. Conventional methods for the detection of pathogens
      in foods are time-consuming and labor-intensive. New advanced rapid methods
      (i.e., polymerase chain reaction, DNA probes) are more sensitive and selective
      than conventional techniques, but many of these tests are inhibited by food
      components, rendering them dependent on slow cultural enrichment. The need for
      alternative methods that will rapidly separate and concentrate bacteria directly
      from food samples, thereby reducing the time required for these new rapid
      detection techniques, is evident. Separation and concentration methods extract
      target bacteria from interfering food components and/or concentrate bacteria to
      detectable levels. This review describes several methods used to separate and/or
      concentrate bacteria in food samples. Several methods discussed here, including
      centrifugation and immunomagnetic separation, have been successfully used,
      individually and in combination, to rapidly separate and/or concentrate bacteria
      from food samples in less time than is required for cultural enrichment.

PMID- 14572238
TI  - A new method for the stereoselective synthesis of alpha-substituted serine amino
      acid analogues.
AB  - [reaction: see text]. A new method was developed for the stereoselective
      synthesis of alpha-substituted serine amino acids. The strategy utilizes a common
      enantiomerically enriched intermediate obtained through an enzymatic
      desymmetrization. A variety of amino acids were synthesized in good ee's through
      nucleophilic acetylide addition reactions and palladium-catalyzed Sonogashira
      couplings.

PMID- 14572239
TI  - Massive parallel catalyst screening: toward asymmetric MCRs.
AB  - [reaction: see text]. Hundreds of Lewis acid/ligand combinations have been
      screened for stereochemical induction in the Passerini multicomponent reaction.
      The combination of titan tetraisopropylate and (4S,5S)-4,5
      bis(diphenylhydroxymethyl)-2,2-dimethyldioxolane was found to give enantiomeric
      excesses between 32% and 42% in several examples. The absolute stereo induction
      of one example was determined chemically and by means of X-ray crystallography.
      This comprises the first asymmetric Passerini reaction and the first example of a
      stereochemical induction in an isocyanide based multicomponent reaction by a
      chiral Lewis acid.

PMID- 14572240
TI  - Inclusion networks of a calix[5]arene-based exoditopic receptor and long-chain
      alkyldiammonium ions.
AB  - [structure: see text]. Tail-to-tail connection of two cone calix[5]arene moieties
      by a rigid p-xylyl spacer affords the new exoditopic receptor 3 featuring two pi
      rich cavities (assembling cores) in a centrosymmetric divergent arrangement, as
      established by a single-crystal X-ray analysis. 1H NMR complexation studies of 3
      with alkyldiammonium ions support the formation of discrete bis-endo-cavity
      complexes and/or capsular assemblies along a polymer chain (polycaps), according
      to the length of the connector.

PMID- 14572241
TI  - Ionic liquid as a suitable phase for multistep parallel synthesis of an array of
      isoxazolines.
AB  - [reaction: see text]. A parallel array of isoxazoline diamides was prepared using
      an ionic liquid [bmim][BF4] as the phase where a three-step procedure (Schotten
      Baumann, 1,3-dipolar cycloaddition, ester amidation with Me3Al) was carried out.
      At the end, selective extraction of the final products with diethyl ether allowed
      simple isolation of the 16 components of the array (Syncore technology).

PMID- 14572242
TI  - The first locked side-chain analogues of calcitriol (1alpha,25-dihydroxyvitamin
      D3) induce vitamin D receptor transcriptional activity.
AB  - [structure: see text]. We describe the synthesis of the first locked side-chain
      analogues of the natural hormone 1alpha,25-(OH)2-D3 and their effects on gene
      transcription in human colon cancer cells. Analogue 2 was more potent than
      1alpha,25-(OH)2-D3 at inducing vitamin D receptor (VDR) transcriptional activity.
      Analogues 3a and 3b show potency similar to that of 1alpha,25-(OH)2-D3, whereas
      3c was less active. The novel analogues efficiently bind VDR in vivo to induce
      transcription from a consensus vitamin D responsive element (VDRE).

PMID- 14572243
TI  - Total synthesis of zincophorin methyl ester.
AB  - [reaction: see text]. A convergent total synthesis of the methyl ester of
      zincophorin, an ionophore antibiotic, has been realized relying on a
      diastereoselective titanium-mediated aldol coupling between the C1-C12 and C13
      C25 subunits. The latter fragment was prepared by using a Carroll-Claisen
      rearrangement.

PMID- 14572244
TI  - Sugar/steroid/sugar conjugates: sensitivity of lipid binding to sugar structure.
AB  - [structure: see text]. Three steroids, each bearing a sugar on rings A and D,
      have been synthesized. Their effect on the "melting" behavior of a lipid bilayer
      depends on whether the sugar is glucose, galactose, or mannose. Packing
      constraints dictate how the lipid bilayer responds to the sugars.

PMID- 14572245
TI  - Acid-catalyzed cyclization of epoxyallylsilanes. An unusual rearrangement
      cyclization process.
AB  - [reaction: see text]. A new route for the synthesis of epoxyallylsilanes bearing
      the phenyldimethylsilyl group is reported that involves silylcupration of allene,
      conjugate addition to enones, and sulfur-ylide-mediated epoxidation. The Lewis
      acid-catalyzed cyclization of these substrates is presented. The expected normal
      products derived from 5-exo and/or 6-endo attack are not observed; instead,
      methylenecyclohexanols resulting from a tandem rearrangement-cyclization process
      are formed.

PMID- 14572247
TI  - Concise synthesis of the chemopreventitive agent (+/-)-deguelin via a key 6-endo
      hydroarylation.
AB  - [reaction: see text]. A concise total synthesis of (+/-)-deguelin was achieved
      with a longest linear sequence of six steps in 68% yield. A key step was the
      platinum-catalyzed 6-endo hydroarylation of an alkynone intermediate.

PMID- 14572246
TI  - Total synthesis and conformational analysis of the antifungal agent (-)-PF1163B.
AB  - [reaction: see text]. (-)-PF1163B, a new macrocyclic antifungal antibiotic
      isolated from Streptomyces sp., has been prepared in eight steps from (S)
      citronellene. The key step is a ring-closing metathesis reaction of an ester and
      amide derivative obtained from a substituted N-methyl-l-tyrosine.

PMID- 14572248
TI  - Westphal reaction in solid-phase.
AB  - [reaction: see text]. A library of cycloimonium salts has been prepared through
      Westphal reaction in solid-phase. By reaction of solid-support-bound azolium or
      azinium acetates 2, 1,2-diketones 4, and base, cycloimonium salts 5 were
      synthesized in good to high yield and purities.

PMID- 14572249
TI  - Polyphosphoric acid trimethylsilyl ester promoted intramolecular acylation of an
      olefin by a carboxylic acid: convenient construction of C-18-functionalized
      delta14-hecogenin acetate.
AB  - [reaction: see text]. Polyphosphoric acid trimethylsilyl ester (PPSE)-promoted
      intramolecular Friedel-Crafts reactions on a nonaromatic carboxylic acid system
      have been investigated. Studies led to the synthesis of C-18 functionalized
      steroidal compounds 5 and 9a-d with strict retention of the spiroketals.
      Isomerization of spiroketal 9e was studied.

PMID- 14572250
TI  - Cd(II) sensing in water using novel aromatic iminodiacetate based fluorescent
      chemosensors.
AB  - [structure: see text]. Compounds 1 and 2 were designed as fluorescent
      chemosensors for Cd(II). For both, a selective determination of Cd(II) over
      Zn(II) was achieved. The fluorescence emission of both was pH-independent and
      switched off between pH 3-11 in 100% water. Whereas the recognition of Cd(II) at
      pH 7.4 gave rise to the formation of charge-transfer complexes (exciplexes) for
      both (lambdamax ca. 500 and 506 nm, respectively), the recognition of Zn(II) only
      switched on the (monomeric) anthracene emission of 2, while for 1 it was red
      shifted (lambdamax = 468 nm).

PMID- 14572251
TI  - Isomerization-cyclization approach to the synthesis of 2-hydroxy-5-alkylidene
      cyclopent-2-enones.
AB  - [reaction: see text]. Propargyl vinyl ketones that are derived from the addition
      of 1-lithio-1-methoxymethoxy-2-ynes to morpholino enamides undergo isomerization
      followed by cyclization to alpha-methylene cyclopentenones upon exposure to
      silica gel.

PMID- 14572252
TI  - On early events in the Pauson-Khand reaction.
AB  - [reaction: see text]. The Magnus Pauson-Khand (PK) mechanism has been studied for
      the first time by electrospray ionization coupled to tandem mass spectrometry. It
      has been found that loss of CO from the PK complex precedes olefin coordination
      and insertion.

PMID- 14572253
TI  - Nitrosative adenine deamination: facile pyrimidine ring-opening in the
      dediazoniation of adeninediazonium ion.
AB  - [reaction: see text]. Dediazoniation of adeninediazonium ion, 1, forms the
      heteroaromatic cation, 2. Ab initio studies at the CCSD(fc)/6-31G**//MP2(full)/6
      31G** level now reveal that the cyclic cation 2 is kinetically and
      thermodynamically unstable with respect to the pyrimidine ring-opened cation, 3.
      The results suggest that 4-cyano-5-isocyano-imidazole, 4, and 4,5
      dicyanoimidazole, 5, might be formed to some extent in nitrosative deaminations
      of adenine.

PMID- 14572254
TI  - Asymmetric total synthesis and stereochemical elucidation of the antitumor agent
      PM-94128.
AB  - [reaction: see text]. PM-94128, a novel depsipeptide antitumor agent, has been
      synthesized for the first time through a highly stereocontrolled route. The key
      steps for the synthesis of the dihydroxyamino acid moiety involve a
      diastereoselective addition of tert-butyl lithiopropiolate to a chiral nitrone
      and a 2,3-dihydro[1,2]oxazin-6-one dihydroxylation. The synthesis serves to
      define the relative as well as the absolute configuration of the natural product
      (bearing five stereogenic centers).

PMID- 14572255
TI  - SmI2/water/amine mediates cleavage of allyl ether protected alcohols: application
      in carbohydrate synthesis and mechanistic considerations.
AB  - [reaction: see text]. SmI2/H2O/amine provides selective cleavage of unsubstituted
      allyl ethers in good to excellent yields. This method is therefore useful in
      deprotection of alcohols and carbohydrates.

PMID- 14572256
TI  - Synthesis of stable seleno[3,4-b]quinoxaline derivatives.
AB  - [reaction: see text]. The unstable seleno[2,3-b]quinoxoline was generated and
      functionalized in situ to give the stable dialdehyde and diester derivatives. The
      dicyano compound was made in several steps from biscyanomethyl selenide and was
      found to be very stable.

PMID- 14572257
TI  - Synthesis of 15N-enriched pseudouridine derivatives.
AB  - [reaction: see text]. A procedure for the chemical synthesis of [3-15N]-labeled
      pseudouridine and a methylated derivative was developed. A suitably protected
      pseudouridine precursor was nitrated at N3 followed by treatment with 15NH4Cl to
      afford the 15N-labeled product in six steps with a 20% yield. This methodology
      will allow for the production of RNAs with [3-15N]pseudouridine and [3-15N
      methyl]pseudouridine at specific locations.

PMID- 14572258
TI  - Aldol reactions of dioxanes derived from tartaric acid. A total synthesis of (+)
      nephrosteranic acid.
AB  - [reaction: see text]. A general enantioselective synthesis of the paraconic acids
      was developed. The key step was a highly stereoselective aldol reaction between a
      dioxane dithioester derived from l-tartaric acid and a suitable aldehyde.

PMID- 14572259
TI  - Synthesis of 4-trifluoromethylated 2-alkyl- and 2,3-dialkyl-substituted
      azetidines.
AB  - [reaction: see text]. A diastereoselective approach to the synthesis of 4
      trifluoromethylated 2-alkyl- and 2,3-dialkylazetidines, including BOC-protected 4
      trifluoromethylazetidin-2-ylcarboxylic acid, was developed via Wittig reaction of
      4-trifluomethylated beta-lactam followed by alkylation and hydrogenation.

PMID- 14572260
TI  - O-nucleophilic amino alcohol acyl-transfer catalysts: the effect of acidity of
      the hydroxyl group on the activity of the catalyst.
AB  - [reaction: see text]. Amino alcohol-derived acyl-transfer catalysts are shown to
      operate by an O-nucleophilic mechanism, and catalysts bearing electron
      withdrawing groups in proximity to the hydroxyl group are found to be more
      active. This is attributed to an increase in the acidity of the hydroxyl group of
      the catalyst.

PMID- 14572261
TI  - Studies on the synthesis of gymnodimine. Stereocontrolled construction of the
      tetrahydrofuran subunit.
AB  - [reaction: see text]. A bis-(2,6-dichlorobenzyl) ether is shown to undergo
      efficient and highly stereoselective intramolecular iodoetherification to yield a
      cis-2,5-disubstituted tetrahydrofuran, thus providing a powerful illustration of
      a stereodirecting effect first noted by Rychnovsky and Bartlett. The
      tetrahydrofuran was transformed into a subunit suitable for incorporation into
      the shellfish toxin gymnodimine.

PMID- 14572262
TI  - Synthetic studies toward the guanacastepenes.
AB  - [reaction: see text]. An asymmetric approach toward the [6-7] ring system of the
      guanacastepenes is described.

PMID- 14572263
TI  - Lewis acid-catalyzed [4 + 3] cycloaddition of 2-(trimethyl silyloxy)acrolein with
      furan. Insight on the nature of the mechanism from a DFT analysis.
AB  - [reaction: see text]. The mechanism for the Lewis acid-catalyzed [4 + 3]
      cycloaddition of 2-(trimethylsilyloxy)acrolein 1 with furan 2 has been studied at
      the B3LYP/6-31G level. This reaction is a three-step process that is initialized
      by the nucleophilic attack of 2 to the beta-conjugated position of 1 to give a
      zwitterionic intermediate IN1. The key step on the formation of the seven
      membered ring is the electrophilic attack of the furan residue to the
      electrophilically activated carbonyl carbon at this intermediate.

PMID- 14572264
TI  - Regioselective synthesis of substituted naphthalenes: a novel de novo approach
      based on a metal-free protocol for stepwise cycloaddition of o
      alkynylbenzaldehyde derivatives with either alkynes or alkenes.
AB  - [reaction: see text]. Iodonium ions, o-alkynyl-substituted carbonyl compounds,
      and alkynes react to give 1-iodonaphthalene derivatives featuring interesting
      substitution patterns. The reaction with alkenes instead of acetylenes affords
      related naphthyl ketone derivatives. These two metal-free processes are conducted
      at room temperature and furnish products in a regioselective manner.

PMID- 14572265
TI  - Stereochemical control of skeletal diversity.
AB  - [reaction: see text]. Substrates having appendages that pre-encode skeletal
      information (sigma-elements) can be converted into products having distinct
      skeletons using a common set of reaction conditions. The sequential use of the
      Ugi 4CC-IMDA reaction, followed by allylation, hydrolysis, and acylation of a
      chiral amino alcohol appendage (sigma-element), leads to substrates for a ROM/RCM
      or RCM reaction. The stereochemistry of the sigma-element and not its
      constitution controls the outcome of the pathway selected. This work illustrates
      the potential of linking stereochemical control to the challenging problem of
      skeletal diversity.

PMID- 14572266
TI  - Synthesis of diprotected monosubstituted hydrazine derivatives from tert-butyl
      carbazates and boronic acids.
AB  - [reaction: see text]. Diprotected monosubstituted hydrazine derivatives have been
      prepared via the reaction of tert-butyl carbazates with boronic acids catalyzed
      by cuprous chloride at room temperature.

PMID- 14572267
TI  - "One-pot" two-step synthesis of aryl sulfur compounds by photoinduced reactions
      of thiourea anion with aryl halides.
AB  - [reaction: see text]. The photoinduced reactions of aryl halides with the
      thiourea anion afford arene thiolate ions in DMSO. These species without
      isolation, and by a subsequent aliphatic nucleophilic substitution, S(RN)1
      reaction, oxidation, or protonation, yield aryl methyl sulfides, diaryl sulfides,
      diaryl disulfides, and aryl thiols with good yields (50-80%). This is a simple
      and convenient approach which involves the use of the commercially available and
      inexpensive thiourea in a "one-pot" two-step process for the synthesis of
      aromatic sulfur compounds.

PMID- 14572268
TI  - Chiral monophosphites derived from carbohydrate: conformational effect in
      catalytic asymmetric hydrogenation.
AB  - [reaction: see text]. The carbohydrate-derived chiral monophosphites with
      additional groups have been synthesized and used for asymmetric hydrogenation of
      dimethyl itaconate and enamides. Up to 99.6% ee and 98.5% ee have been obtained,
      respectively.

PMID- 14572269
TI  - Pyrazine analogues of dipyrrolylquinoxalines.
AB  - [structure: see text]. The synthesis of novel pyrazine derivatives bearing
      pyrrolic substituents is reported; the ability of these systems to bind certain
      biologically relevant anions in dichloromethane is also detailed.

PMID- 14572270
TI  - A new method to study antioxidant capability: hydrogen transfer from phenols to a
      prefluorescent nitroxide.
AB  - [reaction: see text]. Rate constants for hydrogen abstraction from phenols by a
      prefluorescent-TEMPO probe are reported. The nitroxide is employed as a potential
      model of peroxyl radicals. The probe works by nitroxide suppression of the
      fluorescence of the chromophore. The fluorescence is restored when the nitroxide
      abstracts a hydrogen atom to produce the diamagnetic hydroxylamine. The phenols
      studied in this project exhibited rate constants between 0.003 and 0.2 M(-1) s(
      1). A deuterium isotope effect of 10 for TROLOX confirms that the mechanism is
      dominated by hydrogen transfer.

PMID- 14572271
TI  - On the diastereoselectivity of ru-catalyzed [5 + 2] cycloadditions.
AB  - [reaction: see text]. Ru-catalyzed cycloisomerization of cyclopropylenynes
      proceeds with good to high diastereoselectivities to form hexahydroazulenes.

PMID- 14572272
TI  - Facile one-pot synthesis of photochromic pyrans.
AB  - [reaction: see text]. Photochromic pyrans, including [3H]naphtho[2,1-b]pyrans,
      [2H]naphtho[1,2-b]pyrans, indeno-fused naphtho[1,2-b]pyrans, and heteroannulated
      pyrans, were synthesized in excellent yields through a facile one-pot procedure
      by reaction of propargyl alcohol and naphthol or phenol derivatives in the
      presence of 5 mol % PPTS and 2 equiv of (MeO)3CH. Symmetrical and nonsymmetrical
      bispyrans can also be prepared using the protocol.

PMID- 14572273
TI  - Synthesis of highly enantioenriched all-carbon quaternary centers: conjugate
      additions of chiral organolithium nucleophiles to alpha,alpha-dinitrile beta,beta
      disubstituted olefins.
AB  - [reaction: see text]. Highly enantioenriched quaternary centers are obtained by
      the reaction of chiral lithiated intermediates complexed to (-)-sparteine with
      tetrasubstituted, alpha,alpha-dinitrile activated olefins. Lithiated N-Boc-N-Aryl
      benzylamine furnishes products with drs from 78:22 to 95:5, with ers exceeding
      94:6. Lithiated N-Boc-N-Aryl allylamine reactants provide enecarbamate products
      with drs from 55:45 to 99:1, with ers ranging from 87:13 to 97:3.

PMID- 14572274
TI  - Facile synthesis of polyamide dendrimers from unprotected AB2 building blocks.
AB  - [structure: see text]. A fast, inexpensive, and highly efficient synthesis of
      aromatic polyamide dendrimers without the need for protection and deprotection
      steps has been developed. Dendrons and third-generation polyamide dendrimers were
      easily prepared by a convergent approach involving activation of a focal point
      with thionyl chloride, followed by condensation with unprotected AB2 building
      blocks.

PMID- 14572275
TI  - Total synthesis of (+)-cystothiazole A.
AB  - [structure: see text]. The total synthesis of cystothiazole A is described. Key
      steps of the synthesis include an Evans asymmetric catalytic aldol reaction,
      which established the required C4-C5 stereochemistry. The [2,4']-bis(thiazole)
      was obtained applying our methodology of electrophilic activation of amide.
      Semistabilized Wittig reaction between the phosphonium salt 3 and the aldehyde 2
      afforded 1 in nine linear steps and 38% overall yield.

PMID- 14572276
TI  - Novel iodinated diterpenes from a marine cyanobacterium and red alga assemblage.
AB  - [structure: see text]. Tasihalides A and B have been isolated from an assemblage
      of a marine cyanobacterium, belonging to the genus Symploca, and an unidentified
      red alga. The gross structures and relative stereochemistries of these diterpenes
      were elucidated by spectroscopic means. In addition to possessing a novel cage
      structure, the tasihalides represent the only examples of iodinated diterpenes in
      nature.

PMID- 14572277
TI  - Fragmentation of carbohydrate anomeric alkoxyl radicals: a new synthesis of 1,1
      difluoro-1-iodo alditols.
AB  - [reaction: see text]. The beta-fragmentation of 2,2-difluoro-saccharide anomeric
      alkoxyl radicals, generated under oxidative condition by treatment of the
      respective alcohols with (diacetoxyiodo)benzene (DIB) and iodine, afforded 1,1
      difluoro-1-iodo alditols in high yield. The reactivity of the fluorinated radical
      generated by rupture of the C-I bond has been preliminarily assessed by reductive
      deiodination with tributyltin hydride/AIBN and intermolecular allylation using
      the Keck reaction.

PMID- 14572278
TI  - Practical synthesis of sultams via sulfonamide dianion alkylation: application to
      the synthesis of chiral sultams.
AB  - [reaction: see text]. A practical synthesis of sultams was developed via
      intramolecular sulfonamide dianion alkylation. This method has been applied
      toward the synthesis of chiral sultams, which are synthetically valuable as
      chiral auxiliaries.

PMID- 14572280
TI  - Solid-phase polyamine synthesis using piperazine and piperidine building blocks.
AB  - [reaction: see text]. Polyamines containing piperidine and piperazine moieties
      have been synthesized on solid support using SN2 alkylation of resin-bound
      secondary amines with 2-nitrobenzenesulfonates (nosylates). The effect of solvent
      on this alkylation was investigated. The methodology was employed for the total
      synthesis of novel analogues of wasp polyamine toxins (philanthotoxins).

PMID- 14572279
TI  - Use of cerny epoxides for the accelerated synthesis of glycosaminoglycans.
AB  - [reaction: see text]. 1,6:2,3-Dianhydrohexopyranoses (Cerny epoxides) are
      versatile intermediates for the synthesis of glycosaminoglycans. Complex heparan
      and chondroitin sulfate disaccharide synthons can be assembled from a single
      common precursor in a short sequence of steps.

PMID- 14572281
TI  - Improved reagent for electrophilic amination of stabilized carbanions.
AB  - [reaction: see text]. Enolate amination using O-di(p
      methoxyphenyl)phosphinylhydroxylamine 2 is reported. Reagent 2 reacts efficiently
      with stabilized sodium or potassium enolates derived from malonates,
      phenylacetates, and phenylacetonitriles and is sufficiently soluble for use in
      solution at -78 degrees C.

PMID- 14572282
TI  - Efficient and general protocol for the copper-free sonogashira coupling of aryl
      bromides at room temperature.
AB  - [reaction: see text]. A mild and general protocol for the copper-free Sonogashira
      coupling of aryl bromides with acetylenes has been developed. The use of
      (AllylPdCl)2 and P(t-Bu)3 provides the active Pd(0) catalyst that allows
      subsequent coupling of various alkynes at room temperature with good to excellent
      yields.

PMID- 14572283
TI  - A new beta-carbolinone synthesis using a Rh(II)-promoted [3 + 2]-cycloaddition
      and Pd(0) cross-coupling/Heck cyclization chemistry.
AB  - [reaction: see text]. A short and efficient synthesis of the beta-carbolinone
      ring system was achieved using a rhodium(II)-catalyzed [3 + 2]-cycloaddition, a
      Pd(0)-catalyzed C-N amination reaction, and a subsequent intramolecular Heck
      reaction as the key synthetic steps.

PMID- 14572285
TI  - Fullerene-acene chemistry: diastereoselective synthesis of a cis,cis
      tris[60]fullerene adduct of 6,8,15,17-tetraphenylheptacene.
AB  - [structure: see text]. A one-pot, diastereoselective synthesis of a cis,cis
      tris[60]fullerene adduct of 6,8,15,17-tetraphenylheptacene has been demonstrated
      starting from [60]fullerene and 5,7,9,14,16,18-hexahydro-6,8,15,17
      tetraphenylheptacene.

PMID- 14572284
TI  - Fullerene-acene chemistry: single-crystal X-ray structures for a [60]fullerene
      pentacene monoadduct and a cis-bis[60]fullerene adduct of 6,13-diphenylpentacene.
AB  - [structure: see text]. Crystal structures of the cis-bis[60]fullerene adduct of
      6,13-diphenylpentacene (with the closest carbon atoms on adjacent fullerenes only
      3.065(8) angstroms apart) and the [60]fullerene-pentacene monoadduct are in
      remarkably close agreement with the MM2 calculated structures.

PMID- 14572286
TI  - Infinite three-dimensional polymeric metalloporphyrin network via six-coordinate
      Zn(II) and two axial oxygen donors.
AB  - [structure: see text]. An X-ray crystallographic study of zinc(II) 5,15-di-(2
      methoxymethylphenyl)-porphyrin indicates that it forms a coordination polymer
      through ligation of the ether oxygen atoms on the porphyrin peripheries to the
      metal centers of two identical adjacent porphyrins. This gives a novel
      extensively linked, three-dimensional polymeric structure in which the zinc(II)
      metal forms a six-coordination center. The uniquely structured network has
      cavities between 4.81 and 9.27 angstroms, which makes it resemble molecular sieve
      materials.

PMID- 14572287
TI  - A novel and highly efficient two-carbon ring expansion.
AB  - [reaction: see text]. Dynamic gas-phase thermoisomerization (DGPTI) of medium-
      and large-ring 3-vinylcycloalkanones at 600-630 degrees C produces isomeric
      gamma,delta-unsaturated cycloalkanones expanded by two carbon atoms. A reaction
      mechanism involving an open-chain diradical intermediate, followed by
      intramolecular recombination under insertion of the vinyl group is proposed.
      Substituents on the vinyl moiety are transferred locospecifically to the ring
      expanded ketones as corresponding beta- and gamma-substituents, respectively. The
      preparation of extraordinary cyclic allenes can be accomplished by DGPTI (540
      degrees C) of 3-ethinylcyclododecanone.

PMID- 14572288
TI  - Addition of Bu3SnLi to tert-butanesulfinimines as an efficient route to chiral,
      nonracemic alpha-aminoorganostannanes.
AB  - [reaction: see text]. Addition of Bu3SnLi to tert-butanesulfinimines proceeds
      with high diastereoselectivities to provide the expected adducts in excellent
      yields and typically with dr = >99:1. These adducts are readily converted to
      enantiomerically enriched N-Boc-protected alpha-aminoorganostannanes with
      complete retention of configuration.

PMID- 14572290
TI  - Synthetic studies toward FR182877. Remarkable solvent effect in the vinylogous
      morita-baylis-hillman cyclization.
AB  - [reaction: see text]. The intramolecular vinylogous Morita-Baylis-Hillman
      reaction was explored to access the central cyclopentane ring of FR182877. The
      reaction manifold and product distribution is strikingly solvent and substrate
      dependent.

PMID- 14572289
TI  - Efficient route to 2-deoxy beta-O-aryl-d-glycosides via direct displacement of
      glycosyl iodides.
AB  - [reaction: see text]. The conversion of glycals to 2-deoxy glycosyl acetates
      followed by reaction with trimethylsilyl iodide affords the corresponding
      glycosyl iodides, which readily undergo substitution with aryl alkoxy anions to
      provide 2-deoxy-beta-O-aryl glycosides. Direct displacement of the anomeric
      iodide alleviates the need to introduce temporary C-2 stereodirecting groups that
      require subsequent removal. The only observable byproducts from the
      glycosylations result from elimination of HI giving the starting glycals, which
      can be recycled through the reaction sequence.

PMID- 14572291
TI  - A one-pot process for the enantioselective synthesis of amines via reductive
      amination under transfer hydrogenation conditions.
AB  - [reaction: see text]. Cyclic amines may be prepared via a sequence of
      deprotection followed by intramolecular reductive amination of t-Boc-protected
      amino ketones under asymmetric transfer hydrogenation conditions. In cases where
      the corresponding imine reaction proceeds with high enantioselectivity, this is
      reflected in the one-step process.

PMID- 14572292
TI  - Using a temporary silicon connection in stereoselective allylation with
      allylsilanes: application to the synthesis of stereodefined 1,2,4-triols.
AB  - [reaction: see text]. Treatment of aldehyde 6 with TMSOTf, in the presence of a
      Bronsted acid scavenger, effects an intramolecular allylation to provide the
      oxasilacycle 7 as the major diastereoisomer. Tamao oxidation of the C-Si bond in
      7 affords the corresponding 1,2,4-triol 9.

PMID- 14572293
TI  - Iterative organometallic addition to chiral hydroxylated cyclic nitrones: highly
      stereoselective syntheses of alpha,alpha'- and alpha,alpha-substituted
      hydroxypyrrolidines.
AB  - [reaction: see text]. Iteration of organometallic addition to chiral hydroxylated
      pyrroline N-oxides through an addition-oxidation-addition synthetic sequence
      allowed highly stereoselective double alkylation of pyrrolidine at C-2 or at C-2
      and C-5 depending on the regioselectivity of the oxidation step. Application of
      this methodology has been exemplified by the synthesis of the all-substituted
      pyrrolidine alkaloid (-)-codonopsinine and of proline-type amino acid precursors
      possessing a quaternary stereogenic center, whose configuration can be
      controlled.

PMID- 14572295
TI  - The dermatologist's academic portfolio: a template for documenting scholarship
      and service.
AB  - The clinician-teacher of dermatology often seeks recognition for academic
      efforts, the most visible of which is a university appointment with the potential
      for promotion. Success in achieving this goal requires careful planning to ensure
      effective involvement in academic pursuits that serve the mission of the
      university, and there must be concomitant documentation of this involvement. The
      template in this article provides one format for organizing an academic portfolio
      that stimulates prospective documentation and enhances the possibility of
      academic advancement.

PMID- 14572296
TI  - Potential role of estrogens in wound healing.
AB  - Estrogens play a vital role in the development of sexually dimorphic
      characteristics essential for reproduction. In recent years, insight has been
      gained into the role of estrogens in non-reproductive pathophysiological
      processes, including neoplasia, vascular disease and osteoporosis. Intriguingly,
      the skin appears to act as an end-organ target for estrogenic action; marked
      structural and functional skin changes occurring after the menopause can be
      related to altered hormonal profiles. One of the most important consequences of
      such hormonal changes is the age-related delay in cutaneous wound healing,
      leading to substantial morbidity and mortality, and increased costs to health
      services. Reduced estrogen levels have major downstream effects on cellular and
      tissue responses to injury; such downstream effects include impaired cytokine
      signal transduction, unchecked inflammation, and altered protein balance, and
      have a major impact on the rate of wound healing. Further understanding of the
      complex interaction between aging cells and the hormonal micro-environment is
      essential to develop focused therapeutic strategies to improve cutaneous wound
      healing in hypogonadal individuals, including the elderly.

PMID- 14572297
TI  - Optimal treatment of vascular birthmarks.
AB  - Optimal functional and cosmetic outcomes for vascular lesions require a thorough
      preoperative diagnosis of vascular anomalies, since correct classification of
      each vascular lesion has a direct influence on the treatment of choice. Many
      different classification systems have been discussed controversially. Based on
      clinical practicality and significant accuracy of forecast with regard to the
      clinical course of a lesion, Mulliken and Glowacki's biologic classification
      gained most clinical relevance and has become accepted as the official
      classification scheme by the International Society for the Study of Vascular
      Anomalies (ISSVA). Based on comprehensive description of relevant literature
      results, the current communication shall give an overview of differing,
      internationally accepted treatments. Although conservative management can be
      proposed for uncomplicated hemangiomas occurring in infancy, the proliferative
      progression of these lesions provides an adequate indication for treatment, while
      vascular malformations, which usually persist throughout life, always require
      therapeutic intervention if they start to cause clinical symptoms. Based on
      individual parameters (such as diameter, location and growth dynamics), different
      treatments, including cryotherapy, corticosteroids, laser therapy, sclerotherapy,
      surgery, and/or embolization, can be performed successfully. Currently, however,
      none of these treatments represents the solitary treatment of choice.

PMID- 14572298
TI  - Optimal management of hair loss (alopecia) in children.
AB  - Hair loss in children encompasses a wide range of conditions that can be
      congenital or acquired. A congenital hair abnormality may be an isolated finding
      in an otherwise healthy child or may exist as a feature of a clinical syndrome. A
      thorough understanding of basic hair biology and normal hair development enables
      accurate assessment of the child with hair loss. Knowledge of the normal range
      and variation observed in children's hair additionally enhances this assessment.
      Social and cultural factors also influence these norms. The psychological and
      cosmetic importance of hair is immense in our society. The clinical presentation
      of pediatric hair disorders ranges from subtle to disfiguring. Management of hair
      disorders requires a holistic approach to the child and family. Young children
      usually lack self-awareness and it may be the parent who, projecting their own
      concerns onto the child, most acutely feels any associated anxiety. In addition,
      parents of a child with an inherited hair condition often feel guilt, and
      siblings can develop unsupported fears that they may be affected. Hair loss for
      the older child can lead to low self-esteem, depression and humiliation.
      Congenital and hereditary hypotrichosis and hair shaft abnormalities often have
      no effective treatment. There is a variety of treatment options for alopecia
      areata and telogen effluvium, but no single treatment is 100% effective. Tinea
      capitis is an infective condition of the hair that responds readily to the
      appropriate medical therapy. If no effective treatment for the hair loss exists,
      cosmetic camouflage with wigs is the best option.

PMID- 14572299
TI  - Role of topical emollients and moisturizers in the treatment of dry skin barrier
      disorders.
AB  - Emollients and moisturizing creams are used to break the dry skin cycle and to
      maintain the smoothness of the skin. The term 'moisturizer' is often used
      synonymously with emollient, but moisturizers often contain humectants in order
      to hydrate the stratum corneum. Dryness is frequently linked to an impaired
      barrier function observed, for example, in atopic skin, psoriasis, ichthyosis,
      and contact dermatitis. Dryness and skin barrier disorders are not a single
      entity, but are characterized by differences in chemistry and morphology in the
      epidermis. Large differences also exist between moisturizing creams. Moisturizers
      have multiple functions apart from moistening the skin. Similar to other actives,
      the efficacy is likely to depend on the dosage, where compliance is a great
      challenge faced in the management of skin diseases. Strong odor from ingredients
      and greasy compositions may be disagreeable to the patients. Furthermore, low pH
      and sensory reactions, from lactic acid and urea for example, may reduce patient
      acceptance. Once applied to the skin, the ingredients can stay on the surface, be
      absorbed into the skin, be metabolized, or disappear from the surface by
      evaporation, sloughing off, or by contact with other materials. In addition to
      substances considered as actives, e.g. fats and humectants, moisturizers contain
      substances conventionally considered as excipients (e.g. emulsifiers,
      antioxidants, preservatives). Recent findings indicate that actives and
      excipients may have more pronounced effects in the skin than previously
      considered. Some formulations may deteriorate the skin condition, whereas others
      improve the clinical appearance and skin barrier function. For example,
      emulsifiers may weaken the barrier. On the other hand, petrolatum has an
      immediate barrier-repairing effect in delipidized stratum corneum. Moreover, one
      ceramide-dominant lipid mixture improved atopic dermatitis and decreased
      transepidermal water loss (TEWL) in an open-label study in children. In double
      blind studies moisturizers with urea have been shown to reduce TEWL in atopic and
      ichthyotic patients. Urea also makes normal and atopic skin less susceptible
      against irritation to sodium laurilsulfate. Treatments improving the barrier
      function may reduce the likelihood of further aggravation of the disease. In
      order to have optimum effect it is conceivable that moisturizers should be
      tailored with respect to the epidermal abnormality. New biochemical approaches
      and non-invasive instruments will increase our understanding of skin barrier
      disorders and facilitate optimum treatments. The chemistry and function of dry
      skin and moisturizers is a challenging subject for the practicing dermatologist,
      as well as for the chemist developing these agents in the pharmaceutical/cosmetic
      industry.

PMID- 14572300
TI  - Fragrance contact allergy: a clinical review.
AB  - Most people in modern society are exposed daily to fragrance ingredients from one
      or more sources. Fragrance ingredients are also one of the most frequent causes
      of contact allergic reactions. The diagnosis is made by patch testing with a
      mixture of fragrance ingredients, the fragrance mix. This gives a positive patch
      test reaction in about 10% of tested patients with eczema, and the most recent
      estimates show that 1.7-4.1% of the general population are sensitized to
      ingredients of the fragrance mix. Fragrance allergy occurs predominantly in women
      with facial or hand eczema. These women typically have a history of rash to a
      fine fragrance or scented deodorants. Chemical analysis has revealed that well
      known allergens from the fragrance mix are present in 15-100% of cosmetic
      products, including deodorants and fine fragrances, and most often in
      combinations of three to four allergens in the same products. This means that it
      is difficult to avoid exposure, as products labelled as 'fragrance free' have
      also been shown to contain fragrance ingredients, either because of the use of
      fragrance ingredients as preservatives or masking perfumes, or the use of
      botanicals. About 2500 different fragrance ingredients are currently used in the
      composition of perfumes and at least 100 of these are known contact allergens.
      Therefore, it is advisable to supplement standard patch testing with the
      patient's own stay-on cosmetic products, as well as the fragrance chemical
      hydroxyisohexyl-3-cyclohexane carboxaldehyde, which on its own gives responses in
      1-3% of tested patients. The focus in recent years on the ingredients of the
      fragrance mix will probably result in the fragrance industry changing the
      composition of perfumes, and thus make the current diagnostic test less useful.
      New diagnostic tests are under development to identify contact allergy to new
      allergens, reflecting the continuous developments and trends in exposure.

PMID- 14572301
TI  - Cutaneous psammomatous melanotic schwannoma: non-recurrence with surgical
      excision.
AB  - BACKGROUND: Melanotic schwannoma is a pigmented nerve tumor that may be located
      in the skin and express local aggressivity. This tumor may occur singly. It may
      also be part of the Carney complex which consists of various, but specific,
      tumors. OBJECTIVE: We report two cases of subcutaneous melanotic schwannoma
      localized on the trunk in two men aged 37 and 45 years. METHODS: Conventional
      histology and immunohistochemistry were performed. RESULTS: One melanotic
      schwannoma was associated with a cutaneous atypical myxoma and multiple
      melanocytic lesions, all being part of the Carney complex. The other case had no
      associated signs. In both cases, the melanotic schwannoma was completely excised
      and did not recur. CONCLUSION: Melanotic schwannoma is rare and curable by
      surgery. It must not be confused with malignant melanoma and other pigmented
      neoplasms. The Carney complex should be carefully ruled out.

PMID- 14572302
TI  - Cutaneous drug reaction case reports: from the world literature.
AB  - Skin disorders are the most common adverse reactions attributed to drugs. Any
      skin disorder can be imitated, induced or aggravated by drugs. To help you keep
      up-to-date with the very latest skin reactions occurring with both new and
      established drugs, this section of the journal brings you information selected
      from the adverse drug reaction alerting service Reactions Weekly. The following
      case reports are selected from the very latest to be published in the world
      dermatology literature. Any claim of a first report has been verified by a search
      of AdisBase (a proprietary database of Adis International) and Medline. In
      addition, the World Health Organization (WHO) Adverse Drug Reactions database is
      also searched. This database, maintained by the Uppsala Monitoring Centre in
      Sweden, is the largest and most comprehensive adverse drug reaction source in the
      world, with information obtained from National Centers of around 70 affiliate
      countries. Each case report is assessed for seriousness using the FDA MedWatch
      definition of serious (patient outcome is: death; life-threatening;
      hospitalization; disability; congenital anomaly; or requires intervention to
      prevent permanent impairment or damage).

PMID- 14572303
TI  - The effect of hydroxyurea on the phosphorylation of zidovudine and lamivudine in
      human umbilical vein endothelial cells.
AB  - The purpose of this study was to characterize the activation of zidovudine (ZDV)
      and lamivudine (3TC) in human umbilical vein endothelial cells (HUVEC) with and
      without hydroxyurea (HU) pretreatment. HUVEC were pretreated with HU or control
      media for 24 h and then incubated for an additional 3 h with ZDV or 3TC.
      Intracellular concentrations of parent drugs and the phosphorylated forms were
      determined by high-performance liquid chromatography. Pretreatment with HU
      resulted in more than a threefold increase in intracellular concentrations of
      total ZDV, with the major intracellular form being the monophosphate (>80%). The
      relative percentage of each ZDV form was similar between control and HU-treated
      cells. On the other hand, intracellular concentrations of total 3TC increased
      only slightly (14%) with HU pretreatment. Although the parent drug remained the
      major intracellular form of 3TC, there was nearly a 400% increase in the 3TC
      triphosphate after HU pretreatment. These data demonstrate that HU causes a large
      increase in the intracellular accumulation of total ZDV, whereas it increases
      total 3TC only slightly but improves its triphosphorylation. Given the increase
      in intracellular concentrations of ZDV monophosphate after HU pretreatment and
      that the monophosphate has no antiviral activity but is associated with toxicity,
      the use of HU is not a good strategy to improve ZDV activation in human
      endothelium. There is improved production of the active antiviral 3TC
      triphosphate with HU pretreatment. The combination may be beneficial in treating
      potential sanctuary sites such as endothelium.

PMID- 14572304
TI  - Effect of magnesium, high altitude and acute mountain sickness on blood flow
      velocity in the middle cerebral artery.
AB  - Cerebral blood flow is thought to increase at high altitude and in subjects
      suffering from acute mountain sickness (AMS); however, data from the literature
      are contentious. Blood flow velocity in the middle cerebral artery (MCAv) may be
      used as a proxy measure of cerebral blood flow. Using transcranial Doppler
      sonography, MCAv was measured during normo- and hyper-ventilation in subjects who
      participated in a trial that tested the effect of magnesium supplementation on
      the prevention of AMS. First, MCAv was recorded at 353 m (baseline). Subjects
      were then randomized to receive oral magnesium citrate and matching placebo. A
      second measurement was taken after a 24 +/- 2 h ascent from 1130 m to 4559 m
      (altitude I), and a third after a 20-24 h stay at 4559 m (altitude II). Using
      multivariate linear regression, an association was sought between MCAv and
      magnesium supplementation, subjects' age and gender, altitude itself, a temporary
      stay at altitude, and the presence of AMS (Lake Louise Score >6 with ataxia,
      nausea and/or headache). Subjects with AMS had additional Doppler recordings
      immediately before and after rescue medication (oxygen, dexamethasone and
      acetazolamide). Forty-seven subjects had measurements at baseline, 39 (21
      receiving magnesium and 18 placebo) at altitude I and 26 (13 receiving magnesium
      and 13 placebo) at altitude II. During hyperventilation, MCAv decreased
      consistently (for each measurement, P<0.001). Magnesium significantly increased
      MCAv by 8.4 cm.s(-1) (95% confidence interval, 1.8-15), but did not prevent AMS.
      No other factors were associated with MCAv. Eleven subjects had severe AMS
      [median score (range), 11 (8-16)] and, after rescue medication, the median score
      decreased to 3 (range, 0-5; P=0.001), but MCAv remained unchanged (65 +/- 18
      cm.s(-1) before compared with 67 +/- 16 cm.s(-1) after rescue medication;
      P=0.79). MCAv was increased in subjects who received magnesium, but was not
      affected by exposure to high altitude or by severe AMS.

PMID- 14572305
TI  - Magnesium for the prevention and treatment of acute mountain sickness.
AB  - Magnesium is a physiological N-methyl-D-aspartate (NMDA) antagonist. The NMDA
      receptor may be involved in the pathogenesis of acute mountain sickness (AMS). In
      the present study, healthy subjects were randomized to receive either 400 mg of
      oral magnesium citrate (16 mmol) or matching placebo every 8 h for 5 days
      (prevention trial). Subjects then climbed to 4559 m in approx. 24 h and stayed
      there for 48 h. A Lake Louise Score <3 at any time was defined as the absence of
      AMS, whereas a score >6 (with ataxia, headache and nausea) was defined as a
      prevention failure. In a subsequent trial (treatment trial), subjects with a Lake
      Louise Score >6 (with ataxia, headache and/or nausea) were randomized to receive
      either 4 g of intravenous magnesium sulphate (16 mmol) or matching placebo. A
      decrease in the score >50% within 60 min was regarded as a treatment success.
      Dichotomous data were analysed using relative risk (RR) or odds ratio (OR), and
      continuous data using Student's t test or Wilcoxon's rank-sum test. In the
      prevention trial, data from 61 subjects (30 receiving magnesium and 31 placebo)
      were analysed. With oral magnesium, 20% of subjects had no AMS compared with
      16.1% in the placebo group [RR (95% CI), 1.2 (0.4-3.6); where CI is confidence
      interval]. With magnesium, 40% were prevention failures compared with 35.5% in
      the placebo group [RR (95% CI), 1.13 (0.59-2.15)]. The mean time to failure and
      severity of AMS was similar between the two groups. With magnesium, 38.2% had
      loose stools compared with 11.8% in placebo group [RR (95% CI), 3.25 (1.18
      8.97)]. In the treatment trial, 12 subjects received magnesium and 13 received
      the placebo. With intravenous magnesium, 25% were regarded as treatment successes
      compared with none in the placebo group [OR (95% CI), 9.71 (0.91-103.4)]. With
      magnesium, mean (+/- S.D.) scores decreased from 11.6 +/- 1.7 before treatment to
      9.0 +/- 3.5 after treatment (P=0.009); scores remained unchanged in the placebo
      group. With magnesium, 75% of subjects experienced a transient flushing compared
      with 7.7% in the placebo group [RR (95% CI), 0.05 (0.01-0.25)]. In conclusion,
      oral magnesium does not prevent AMS. In subjects with established AMS,
      intravenous magnesium reduces the severity of symptoms to some extent, but this
      effect is of no clinical importance.

PMID- 14572306
TI  - A single-fibre study of the relationship between MHC and TnC isoform composition
      in rat skeletal muscle.
AB  - In the present study, we investigated the possibility that MHC (myosin heavy
      chain) and TnC (troponin C) isoforms exist in specific combinations in rat
      skeletal-muscle fibres. Single fibres (numbering 245) from soleus (predominantly
      slow-twitch) and sternomastoid (predominantly fast-twitch) muscles of adult rats
      were analysed for MHC and TnC isoform composition, using alanine-SDS/PAGE for
      separating MHC isoforms, and a novel method (based on the previously reported
      influence of Ca2+ on the mobility of Ca2+-binding proteins in SDS gels) for
      unequivocal identification of TnC isoforms in single-fibre segments. In this
      study, all fibres that contained only one MHC isoform (slow or fast) contained
      only the matching TnC isoform and all fibres that contained multiple fast MHC
      isoforms contained only the fast TnC isoform. Fibres expressing both slow and
      fast MHC isoforms displayed either both TnC isoforms or only one TnC isoform of a
      type depending on the relative proportion of fast/slow MHC present. Our results
      suggest a close relationship between MHC and TnC isoform composition in non
      transforming skeletal muscles of adult rat.

PMID- 14572307
TI  - Adenosine transport in peripheral blood lymphocytes from Lesch-Nyhan patients.
AB  - We postulated that adenosine function could be related to some of the
      neurological features of Lesch-Nyhan syndrome and therefore characterized
      adenosine transport in PBLs (peripheral blood lymphocytes) obtained from Lesch
      Nyhan patients (PBL(LN)) and from controls (PBL(C)). Adenosine transport was
      significantly lower in PBL(LN) when compared with that in PBL(C) and a
      significantly lower number of high affinity sites for
      [(3)H]nitrobenzylthioinosine binding were quantified per cell ( B (max)) in
      PBL(LN) when compared with that in PBL(C). After incubation with 25 microM
      hypoxanthine, adenosine transport was significantly decreased in PBL(LN) with
      respect to PBL(C). Hypoxanthine incubation lowers [(3)H]nitrobenzylthioinosine
      binding in PBL(C), with respect to basal conditions, but does not affect it in
      PBL(LN). This indicates that hypoxanthine affects adenosine transport in control
      and hypoxanthine-guanine phosphoribosyltransferase-deficient cells by different
      mechanisms.

PMID- 14572308
TI  - Evidence for a second peptide cleavage in the C-terminal domain of rodent
      intestinal mucin Muc3.
AB  - Rat intestinal mucin Muc3 (rMuc3), like its human homologue (MUC3) and several
      other membrane mucins, contains a C-terminally located SEA (sea urchin sperm
      protein, enterokinase and agrin) module, with an intrinsic proteolytic site
      sequence G downward arrow SIVV (where G downward arrow S is the glycine serine
      cleavage site). As shown previously [Wang, Khatri and Forstner (2002) Biochem. J.
      366, 623-631], expression of the C-terminal domain of rMuc3 in COS-1 cells yields
      a V5 epitope-tagged N-terminal glycopeptide of 30 kDa and a Myc- and His epitope
      tagged C-terminal glycopeptide of 49 kDa. The present study shows that the 49 kDa
      membrane-anchored fragment undergoes a further cleavage reaction which decreases
      its size to 30 kDa. Western blotting, pulse-chase metabolic incubations,
      immunoprecipitation and deglycosylation with N-glycosidase F were used to detect
      and identify the proteolytic products. Both the first and second cleavages are
      presumed to facilitate solubilization of Muc3 at the apical surface of
      enterocytes and/or enhance the potential for Muc3 to participate in ligand
      receptor and signal transduction events for enterocyte function in vivo.

PMID- 14572309
TI  - Expression patterns and different subcellular localization of the growth factors
      HDGF (hepatoma-derived growth factor) and HRP-3 (HDGF-related protein-3) suggest
      functions in addition to their mitogenic activity.
AB  - HDGF (hepatoma-derived growth factor) and the HRPs (HDGF-related proteins)
      comprise a family of six proteins which display high identity in their N
      terminus, but differ at the C-terminus. Here we investigate the patterns of
      expression of HDGF and HRP-3, by generating antisera specifically recognizing
      each growth factor. Whereas HRP-3 protein is expressed only in brain, HDGF can be
      found in a broad range of tissues, with highest levels in brain, testis, lung and
      spleen. The expression of HDGF and HRP-3 was found to be regulated during brain
      development, with highest levels around birth, followed by a decline until
      postnatal day 9. Interestingly, expression of HRP-3 increases again in adult
      brain. In situ hybridization and immunohistochemistry of cerebellar, cerebral and
      hippocampal brain slices showed that expression of both growth factors is not
      limited to areas of high proliferative activity. Both mRNAs and proteins are
      expressed in neuronal as well as glial cells. Immunocytochemistry of cultured
      neocortical neurons revealed that HDGF and HRP-3 can be found in the nucleus as
      well as the cytoplasm. HDGF is restricted to the neuronal soma, whereas HRP-3 can
      also be found in neurites. Thus the expression of HDGF and HRP-3 in
      differentiated cells, post-mitotic neurons and primary cultures of rat neocortex
      points to functions in brain that might not be limited to proliferation. In
      addition, their simultaneous expression in the same cell and their different
      subcellular localization in cultured neurons suggest different functions of HDGF
      and HRP-3 within single cells.

PMID- 14572310
TI  - Structure and regulation of the mDot1 gene, a mouse histone H3 methyltransferase.
AB  - The nucleotide sequence data reported have been deposited in the DDBJ, EMBL,
      GenBank(R) and GSDB Nucleotide Sequence Databases under accession numbers
      AY196089, AY196090, AY376663, AY377920 and AY376664. Recently, a new class of
      histone methyltransferases that plays an indirect role in chromatin silencing by
      targeting a conserved lysine residue in the nucleosome core was described, namely
      the Dot1 (disruptor of telomeric silencing) family [Feng, Wang, Ng, Erdjument
      Bromage, Tempst, Struhl and Zhang (2002) Curr. Biol. 12, 1052-1058; van Leeuwen,
      Gafken and Gottschling (2002) Cell (Cambridge, Mass.) 109, 745-756; Ng, Feng,
      Wang, Erdjument-Bromage, Tempst, Zhang and Struhl (2002) Genes Dev. 16, 1518
      1527]. In the present study, we report the isolation, genomic organization and in
      vivo expression of a mouse Dot1 homologue (mDot1). Expressed sequence tag
      analysis identified five mDot1 mRNAs (mDot1a-mDot1e) derived from alternative
      splicing. mDot1a and mDot1b encode 1540 and 1114 amino acids respectively,
      whereas mDot1c-mDot1e are incomplete at the 5'-end. mDot1a is closest to its
      human counterpart (hDot1L), sharing 84% amino acid identity. mDot1b is truncated
      at its N- and C-termini and contains an internal deletion. The five mDot1
      isoforms are encoded by 28 exons on chromosome 10qC1, with exons 24 and 28
      further divided into two and four sections respectively. Alternative splicing
      occurs in exons 3, 4, 12, 24, 27 and 28. Northern-blot analysis with probes
      corresponding to the methyltransferase domain or the mDot1a-coding region
      detected 7.6 and 9.5 kb transcripts in multiple tissues, but only the 7.6 kb
      transcript was evident in mIMCD3-collecting duct cells. Transfection of mDot1a
      EGFP constructs (where EGFP stands for enhanced green fluorescent protein) into
      human embryonic kidney (HEK)-293T or mIMCD3 cells increased the methylation of H3
      K79 but not H3-K4, -K9 or -K36. Furthermore, DMSO induced mDot1 gene expression
      and methylation specifically at H3-K79 in mIMCD3 cells in a time- and dose
      dependent manner. Collectively, these results add new members to the Dot1 family
      and show that mDot1 is involved in a DMSO-mediated signal-transduction pathway in
      collecting duct cells.

PMID- 14572311
TI  - Residue 182 influences the second step of protein-tyrosine phosphatase-mediated
      catalysis.
AB  - Previous enzyme kinetic and structural studies have revealed a critical role for
      Asp181 (PTP1B numbering) in PTP (protein-tyrosine phosphatase)-mediated
      catalysis. In the E-P (phosphoenzyme) formation step, Asp181 functions as a
      general acid, while in the E-P hydrolysis step it acts as a general base. Most of
      our understanding of the role of Asp181 is derived from studies with the Yersinia
      PTP and the mammalian PTP1B, and to some extent also TC (T-cell)-PTP and the
      related PTPa and PTPe. The neighbouring residue 182 is a phenylalanine in these
      four mammalian enzymes and a glutamine in Yersinia PTP. Surprisingly, little
      attention has been paid to the fact that this residue is a histidine in most
      other mammalian PTPs. Using a reciprocal single-point mutational approach with
      introduction of His182 in PTP1B and Phe182 in PTPH1, we demonstrate here that
      His182-PTPs, in comparison with Phe182-PTPs, have significantly decreased kcat
      values, and to a lesser degree, decreased kcat/Km values. Combined enzyme
      kinetic, X-ray crystallographic and molecular dynamics studies indicate that the
      effect of His182 is due to interactions with Asp181 and with Gln262. We conclude
      that residue 182 can modulate the functionality of both Asp181 and Gln262 and
      therefore affect the E-P hydrolysis step of PTP-mediated catalysis.

PMID- 14572312
TI  - rIFN-gamma-mediated growth suppression of platinum-sensitive and -resistant
      ovarian tumor cell lines not dependent upon arginase inhibition.
AB  - BACKGROUND: Arginine metabolism in tumor cell lines can be influenced by various
      cytokines, including recombinant human interferon-gamma (rIFN-gamma), a cytokine
      that shows promising clinical activity in epithelial ovarian cancer (EOC).
      METHODS: We examined EOC cell lines for the expression of arginase in an
      enzymatic assay and for transcripts of arginase I and II, inducible nitric oxide
      synthase (iNOS), and indoleamine 2,3-dioxygenase (IDO) by reverse transcription
      polymerase chain reaction. The effects of rIFN-gamma on arginase activity and on
      tumor cell growth inhibition were determined by measuring [3H]thymidine uptake.
      RESULTS: Elevated arginase activity was detected in 5 of 8 tumor cell lines, and
      analysis at the transcriptional level showed that arginase II was involved but
      arginase I was not. rIFN-gamma reduced arginase activity in 3 EOC cell lines but
      increased activity in the 2008 cell line and its platinum-resistant subline,
      2008.C13. iNOS transcripts were not detected in rIFN-gamma-treated or untreated
      cell lines. In contrast, IDO activity was induced or increased by rIFN-gamma.
      Suppression of arginase activity by rIFN-gamma in certain cell lines suggested
      that such inhibition might contribute to its antiproliferative effects. However,
      supplementation of the medium with polyamine pathway products did not interfere
      with the growth-inhibitory effects of rIFN-gamma EOC cells. CONCLUSIONS:
      Increased arginase activity, specifically identified with arginase II, is present
      in most of the tested EOC cell lines. rIFN-gamma inhibits or stimulates arginase
      activity in certain EOC cell lines, though the decrease in arginase activity does
      not appear to be associated with the in vitro antiproliferative activity of rIFN
      gamma. Since cells within the stroma of EOC tissues could also contribute to
      arginine metabolism following treatment with rIFN-gamma or rIFN-gamma-inducers,
      it would be helpful to examine these effects in vivo.

PMID- 14572313
TI  - TGFbeta1 activates c-Jun and Erk1 via alphaVbeta6 integrin.
AB  - Transforming growth factor beta (TGFbeta) plays an important role in animal
      development and many cellular processes. A variety of cellular functions that are
      required for tumor metastasis are controlled by integrins, a family of cell
      adhesion receptors. Overexpression of alphaVbeta6 integrin is associated with
      lymph node metastasis of gastric carcinomas. It has been demonstrated that a full
      TGFbeta1 signal requires both alphaVbeta6 integrin and SMAD pathway. TGFbeta1
      binds to alphaVbeta6 via the DLXXL motif, a freely accessible amino acid sequence
      in the mature form of TGFbeta1. Binding of mature TGFbeta1 to alphaVbeta6 leads
      to immobilization and tyrosine phosphorylation of proteins, which are associated
      with focal adhesions, a hallmark of integrin-mediated signal transduction. Here,
      we show that binding of mature TGFbeta1 recruits the mitogen-activated protein
      kinase kinase kinase 1 (MEKK1), a mediator of c-Jun activation, and the
      extracellular signaling-regulated kinase-1 (Erk1) to focal adhesions. In
      addition, the p21-activated kinase 1 (PAK1) is associated with focal adhesions
      and differentially phosphorylated upon TGFbeta1 stimulation. We conclude that
      TGFbeta1 activates c-Jun via the MEKK1/p38 MAP kinase pathway and influences
      cytoskeletal organization. These finding may provide a link between TGFbeta1 and
      the metastatic behavior of cancers.

PMID- 14572314
TI  - The development and implementation of a curriculum to improve clinicians' self
      directed learning skills: a pilot project.
AB  - BACKGROUND: Clinicians need self-directed learning skills to maintain competency.
      The objective of this study was to develop and implement a curriculum to teach
      physicians self-directed learning skills during inpatient ward rotations.
      METHODS: Residents and attendings from an internal medicine residency were
      assigned to intervention or control groups; intervention physicians completed
      self-directed learning curricular exercises. RESULTS: Among the 43 intervention
      physicians, 21 (49%) completed pre- and post-curriculum tests; and 10 (23%)
      completed the one-year test. Immediately after exposure to the curriculum, the
      proportion of physicians defining short- and long-term learning goals increased
      [short-term: 1/21 (5%) to 11/21 (52%), p = 0.001; long-term: 2/21 (10%) to 15/21
      (71%), p = 0.001]. There were no significant changes post-curriculum in the
      quantity or quality of clinical question asking. The physicians' mean self
      efficacy (on a 100-point scale) improved for their abilities to develop a plan to
      keep up with the medical literature (59 vs. 72, p = 0.04). The effects of the
      curriculum on self-reported learning behaviors was maintained from the immediate
      post-curriculum test to the one-year post curriculum test: [short-term learning
      goals: 1/21 (5%) pre-, 11/21 (52%) immediately post-, and 5/10 (50%) one-year
      after the curriculum (p = 0.0075 for the pre- vs one-year comparison); long-term
      learning goals: 2/21 (10%) pre-, 15/21 (71%) immediately post-, and 7/10 (70%)
      one-year (p = 0.0013 for the pre- vs one-year comparison). At one-year, half of
      the participants reported changed learning behaviors. CONCLUSIONS: A four-week
      curriculum may improve self-directed learning skills.

PMID- 14572315
TI  - Regulation of amylin release from cultured rabbit gastric fundic mucosal cells.
AB  - BACKGROUND: Amylin (islet amyloid polypeptide) is a hormone with suggested roles
      in the regulation of glucose homeostasis, gastric motor and secretory function
      and gastroprotection. In the gastric mucosa amylin is found co-localised with
      somatostatin in D-cells. The factors regulating gastric amylin release are
      unknown. In this study we have investigated the regulation of amylin release from
      gastric mucosal cells in primary culture. Rabbit fundic mucosal cells enriched
      for D-cells by counterflow elutriation were cultured for 40 hours. Amylin and
      somatostatin release over 2 hours in response to agonists were assessed. RESULTS:
      Amylin release was significantly enhanced by activation of protein kinase C with
      phorbol-12-myristate-13-acetate, adenylate cyclase with forskolin and elevation
      of intracellular calcium with A23187. Cholecystokinin (CCK), epinephrine and
      glucagon-like peptide-1 (GLP-1) each stimulated amylin release in a dose
      dependent manner. Maximal CCK-stimulated release was greater than either
      epinephrine or GLP-1, even when the effects of the latter two were enhanced by
      isobutylmethylxanthine. Stimulated amylin release was significantly inhibited by
      carbachol (by 51-59%) and octreotide (by 33-42%). Somatostatin release paralleled
      that of amylin. CONCLUSIONS: The cultured D-cell model provides a means of
      studying amylin release. Amylin secretion is stimulated by receptor-dependent and
      -independent activation of Ca2+/protein kinase C and adenylate cyclase pathways.
      Inhibition involves activation of muscarinic receptors and auto-regulation by
      somatostatin.

PMID- 14572317
TI  - Current HIV/AIDS end-of-life care in sub-Saharan Africa: a survey of models,
      services, challenges and priorities.
AB  - BACKGROUND: In response to increased global public health funding initiatives to
      HIV/AIDS care in Africa, this study aimed to describe practice models, strategies
      and challenges to delivering end-of-life care in sub-Saharan Africa. METHODS: A
      survey end-of-life care programs was conducted, addressing the domains of service
      aims and configuration, barriers to pain control, governmental endorsement and
      strategies, funding, monitoring and evaluation, and research. Both closed and
      qualitative responses were sought. RESULTS: Despite great structural challenges,
      data from 48 programs in 14 countries with a mean annual funding of US 374,884
      dollars demonstrated integrated care delivery across diverse settings. Care was
      commonly integrated with all advanced disease care (67%) and disease stages (65%
      offering care from diagnosis). The majority (98%) provided home-based care for a
      mean of 301 patients. Ninety-four percent reported challenges in pain control
      (including availability, lack of trained providers, stigma and legal
      restrictions), and 77% addressed the effects of poverty on disease progression
      and management. Although 85% of programs reported Government endorsement, end-of
      life and palliative care National strategies were largely absent. CONCLUSIONS:
      The interdependent tasks of expanding pain control, balancing quality and
      coverage of care, providing technical assistance in monitoring and evaluation,
      collaborating between donor agencies and governments, and educating policy makers
      and program directors of end-of-life care are all necessary if resources are to
      reach their goals.

PMID- 14572316
TI  - Feeding behaviour of free-ranging walruses with notes on apparent dextrality of
      flipper use.
AB  - BACKGROUND: Direct observations of underwater behaviour of free-living marine
      mammals are rare. This is particularly true for large and potentially dangerous
      species such as the walrus (Odobenus rosmarus). Walruses are highly specialised
      predators on benthic invertebrates - especially bivalves. The unique feeding
      niche of walruses has led to speculations as to their underwater foraging
      behaviour. Based on observations of walruses in captivity and signs of predation
      left on the sea floor by free-living walruses, various types of feeding behaviour
      have been suggested in the literature. In this study, however, the underwater
      feeding behaviour of wild adult male Atlantic walruses (O. r. rosmarus) is
      documented for the first time in their natural habitat by scuba-divers. The video
      recordings indicated a predisposition for use of the right front flipper during
      feeding. This tendency towards dextrality was explored further by examining a
      museum collection of extremities of walrus skeletons. RESULTS: During July and
      August 2001, twelve video-recordings of foraging adult male walruses were made in
      Young Sound (74 degrees 18 N; 20 degrees 15 V), Northeast Greenland. The
      recordings did not allow for differentiation among animals, however based on
      notes by the photographer at least five different individuals were involved. The
      walruses showed four different foraging behaviours; removing sediment by beating
      the right flipper, removing sediment by beating the left flipper, removing
      sediment by use of a water-jet from the mouth and rooting through sediment with
      the muzzle. There was a significant preference for using right flipper over left
      flipper during foraging. Measurements of the dimensions of forelimbs from 23
      walrus skeletons revealed that the length of the right scapula, humerus, and ulna
      was significantly greater than that of the left, supporting our field
      observations of walruses showing a tendency of dextrality in flipper use.
      CONCLUSION: We suggest that the four feeding behaviours observed are typical of
      walruses in general, although walruses in other parts of their range may have
      evolved other types of feeding behaviour. While based on small sample sizes both
      the underwater observations and skeletal measurements suggest lateralized limb
      use, which is the first time this has been reported in a pinniped.

PMID- 14572318
TI  - Cystadenocarcinoma of the appendix: an incidental imaging finding in a patient
      with adenocarcinomas of the ascending and the sigmoid colon.
AB  - BACKGROUND: Primary adenocarcinomas of the appendix are uncommon. Mucoceles that
      result from mucinous adenocarcinomas of the appendix may be incidentally detected
      on imaging. CASE PRESENTATION: A case of a mucocele of the appendix, due to
      cystadenocarcinoma, is presented as an incidental imaging finding in a female, 86
      year-old patient. The patient was admitted due to rectal hemorrhage and underwent
      colonoscopy, x-ray, US and CT. Adenocarcinoma of the ascending colon, adenomatous
      polyp of the sigmoid colon and a cystic lesion in the right iliac fossa were
      diagnosed. The cystic lesion was characterized as mucocele. The patient underwent
      right hemicolectomy, excision of the mucocele and sigmoidectomy. She recovered
      well and in two-year follow-up is free from cancer. CONCLUSIONS: Preoperative
      diagnosis of an underlying malignancy in a mucocele is important for patient
      management, but it is difficult on imaging studies. Small lymph nodes or soft
      tissue stranding in the surrounding fat on computed tomography examination may
      suggest the possibility of malignancy.

PMID- 14572319
TI  - Directed neuronal differentiation of human embryonic stem cells.
AB  - BACKGROUND: We have developed a culture system for the efficient and directed
      differentiation of human embryonic stem cells (HESCs) to neural precursors and
      neurons.HESC were maintained by manual passaging and were differentiated to a
      morphologically distinct OCT-4+/SSEA-4- monolayer cell type prior to the
      derivation of embryoid bodies. Embryoid bodies were grown in suspension in serum
      free conditions, in the presence of 50% conditioned medium from the human
      hepatocarcinoma cell line HepG2 (MedII). RESULTS: A neural precursor population
      was observed within HESC derived serum free embryoid bodies cultured in MedII
      conditioned medium, around 7-10 days after derivation. The neural precursors were
      organized into rosettes comprised of a central cavity surrounded by ring of
      cells, 4 to 8 cells in width. The central cells within rosettes were
      proliferating, as indicated by the presence of condensed mitotic chromosomes and
      by phosphoHistone H3 immunostaining. When plated and maintained in adherent
      culture, the rosettes of neural precursors were surrounded by large interwoven
      networks of neurites. Immunostaining demonstrated the expression of nestin in
      rosettes and associated non-neuronal cell types, and a radial expression of Map-2
      in rosettes. Differentiated neurons expressed the markers Map-2 and Neurofilament
      H, and a subpopulation of the neurons expressed tyrosine hydroxylase, a marker
      for dopaminergic neurons. CONCLUSION: This novel directed differentiation
      approach led to the efficient derivation of neuronal cultures from HESCs,
      including the differentiation of tyrosine hydroxylase expressing neurons. HESC
      were morphologically differentiated to a monolayer OCT-4+ cell type, which was
      used to derive embryoid bodies directly into serum free conditions. Exposure to
      the MedII conditioned medium enhanced the derivation of neural precursors, the
      first example of the effect of this conditioned medium on HESC.

PMID- 14572321
TI  - Considerations for the development and practice of cascade impaction testing,
      including a mass balance failure investigation tree.

PMID- 14572322
TI  - Assessment of handling of inhaler devices in real life: an observational study in
      3811 patients in primary care.
AB  - The correct use of inhalation devices is an inclusion criterion for all studies
      comparing inhaled treatments. In real life, however, patients may make many
      errors with their usual inhalation device, which may negate the benefits observed
      in clinical trials. Our study was undertaken to compare inhalation device
      handling in real life. A total of 3811 patients treated for at least 1 month with
      an inhalation device (Aerolizer, Autohaler, Diskus, pressurized metered dose
      inhaler (pMDI), or Turbuhaler) were included in this observational study
      performed in primary care in France between February 1st and July 14th, 2002.
      General practitioners had to assess patient handling of their usual inhaler
      device with the help of a checklist established for each inhaler model, from the
      package leaflet. Seventy-six percent of patients made at least one error with
      pMDI compared to 49-55% with breath-actuated inhalers. Errors compromising
      treatment efficacy were made by 11-12% of patients treated with Aerolizer,
      Autohaler, or Diskus compared to 28% and 32% of patients treated with pMDI and
      Turbuhaler, respectively. Overestimation of good inhalation by general
      practitioners was maximal for Turbuhaler (24%), and lowest for Autohaler and pMDI
      (6%). Ninety percent of general practitioners felt that participation in the
      study would improve error detection. These results suggest that there are
      differences in the handling of inhaler devices in real life in primary care that
      are not taken into account in controlled studies. There is a need for continued
      education of prescribers and users in the proper use of these devices to improve
      treatment efficacy.

PMID- 14572323
TI  - Lung volume is a determinant of aerosol bolus dispersion.
AB  - The technique of inhaling a small volume element labeled with particles ("aerosol
      bolus") can be used to assess convective gas mixing in the lung. While a bolus
      undergoes mixing in the lung, particles are dispersed in an increasing volume of
      the respired air. However, determining factors of bolus dispersion are not yet
      completely understood. The present study tested the hypothesis that bolus
      dispersion is related, among others, to the total volume in which the bolus is
      allowed to mix--i.e., to the individual lung size. Bolus dispersion was measured
      in 32 anesthetized, mechanically ventilated dogs with total lung capacities
      (TLCs) of 1.1-2.5 L. Six-milliliter aerosol boluses were introduced at various
      preselected time-points during inspiration to probe different volumetric lung
      depths. Dispersion (SD) was determined by moment analysis of particle
      concentrations in the expired air. We found linear correlations between SD at a
      given lung depth and the individual end-inspiratory lung volume (V(L)). The
      relationship was tightest for boluses inhaled deepest into the lungs: SD(40) =
      0.068 V(L) - 1.77, r(2) = 0.59. Normalizing SD to V(L) abolished this dependency
      and resulted in a considerable reduction of inter-individual variability as
      compared to the uncorrected measurements. These data indicate that lung size
      influences measurements of bolus dispersion. It therefore appears reasonable to
      apply a normalization procedure before interpreting the data. Apart from a
      reduction in measurement variability, this should help to separate the effects on
      bolus dispersion of altered lung volumes and altered mixing processes in diseased
      lungs.

PMID- 14572324
TI  - Aerosol drug delivery using heliox and nebulizer reservoirs: results from an MRI
      based pediatric model.
AB  - An MRI-based model of the mouth, throat, and upper airways of a 5-year-old boy is
      used to evaluate methods for increasing the nebulized drug dose delivered to the
      lungs. Four methods are considered: (1) standard nebulizer delivery with air, (2)
      delivery with 70/30 helium-oxygen (heliox), (3) delivery with air and an aerosol
      conserving reservoir, and (4) delivery with heliox and a reservoir. When
      comparing air and heliox, delivery flowrates were adjusted so that the aerosols
      produced were of similar size. The reservoir utilized was the Medicator Aerosol
      Maximizer (Healthline Medical, Baldwin Park, CA). It conserves the aerosol
      generated by the nebulizer during exhalation and makes it available for the next
      inhalation. Technetium-DTPA was utilized. The standard nebulizer driven by air
      delivered 2.2% of the dose loaded into the nebulizer to the lungs as fine
      droplets, versus 3.3% for the nebulizer with heliox (50% increase; p = 0.002 vs.
      air), 2.9% for the nebulizer plus reservoir driven by air (32% increase; p = 0.02
      vs. no reservoir), and 4.0% for the nebulizer plus reservoir driven by heliox
      (82% increase; p = 0.002 vs. air without reservoir). The increased pulmonary dose
      when heliox was utilized occurred because of decreased deposition within the
      nebulizer and other delivery equipment. The increased pulmonary dose when the
      reservoirs were utilized occurred due to a decrease in the dose expelled from the
      nebulizer by exhalation.

PMID- 14572325
TI  - Parents' adherence with nebulizer treatment of their children when using an
      adaptive aerosol delivery (AAD) system.
AB  - The objective of this study was to analyze data on parents' adherence to their
      child's prescribed nebulizer treatment regimen and compliance with the demands of
      the nebulizer and the face mask. Data on adherence and compliance were recorded
      in a 24-week double-blind, randomized, parallel-group study with budesonide
      inhalation suspension in 125 young children with mild to moderate asthma.
      Budesonide was administered with an Adaptive Aerosol Delivery (AAD) system, which
      recorded adherence to treatment and compliance with the AAD system. A total of
      35,481 treatments were recorded and analyzed. A study questionnaire regarding the
      parents' and children's acceptance of the AAD system has also been analyzed. The
      adherence to the treatment regimen was 91.3%, and the compliance with the AAD
      system was 90.4%. True adherence, the product of adherence and compliance, was
      82.5%. Approximately 90% of the parents found the face mask easy to seal and the
      AAD equipment easy to use, and over 90% of the children accepted it within 1
      week. In conclusion, the results indicate that the AAD system could be of real
      clinical advantage for treatment of asthma in young children.

PMID- 14572326
TI  - Next generation pharmaceutical impactor (a new impactor for pharmaceutical
      inhaler testing). Part I: Design.
AB  - A new cascade impactor has been designed specifically for pharmaceutical inhaler
      testing. This impactor, called the Next Generation Pharmaceutical Impactor (NGI),
      has seven stages and is intended to operate at any inlet flow rate between 30 and
      100 L/min. It spans a cut size (D50) range from 0.54-microm to 11.7-microm
      aerodynamic diameter at 30 L/min and 0.24 microm to 6.12 microm at 100 L/min. The
      aerodynamics of the impactor follow established scientific principles, giving
      confident particle size fractionation behavior over the design flow range. The
      NGI has several features to enhance its utility for inhaler testing. One such
      feature is that particles are deposited on collection cups that are held in a
      tray. This tray is removed from the impactor as a single unit, facilitating quick
      sample turn-around times if multiple trays are used. For accomplishing drug
      recovery, the user can add up to approximately 40 mL of an appropriate solvent
      directly to the cups. Another unique feature is a micro-orifice collector (MOC)
      that captures in a collection cup extremely small particles normally collected on
      the final filter in other impactors. The particles captured in the MOC cup can be
      analyzed in the same manner as the particles collected in the other impactor
      stage cups. The user-friendly features and the aerodynamic design principles
      together provide an impactor well suited to the needs of the inhaler testing
      community.

PMID- 14572327
TI  - Next generation pharmaceutical impactor (a new impactor for pharmaceutical
      inhaler testing). Part II: Archival calibration.
AB  - A new seven-stage cascade impactor, the Next Generation Pharmaceutical Impactor
      (NGI), has been developed for the pharmaceutical industry. A calibration
      following "good laboratory practice (GLP)" procedures has been performed on a
      specific archival NGI, deemed to be representative of all NGIs. Thus, this
      impactor had nozzle dimensions for each stage manufactured close to the middle of
      the tolerance band for the design specification, and therefore the average nozzle
      diameter was equal to the nominal value for that stage. An essential feature of
      the NGI is that it is designed to operate at any flow rate between 30 and 100
      L/min. Thus, the calibration was made at inlet flow rates of 30, 60 and 100 L/min
      representing the lower bound, mid-region and upper bound of the specified range
      of operation for the impactor. The calibration data were then used to develop
      equations that predict the particle cut size for all components of the impactor
      at any flow rate from 30 to 100 L/min.

PMID- 14572328
TI  - The effect of breathing pattern on nebulizer drug delivery.
AB  - The significance of using breathing patterns with simplified functional shapes in
      vented jet nebulizer research is examined. This study is comprised of three
      parts: (1) The measurement and analysis of human breathing patterns, (2) the
      subsequent in vitro testing of the effects of breathing pattern differences using
      a consistent bench test method, and (3) a computer modeling of these effects on
      the estimated regional drug deposition in the human lung. Breathing through a
      Pari LC-Star nebulizer caused statistically significant changes (p < or = 0.05)
      in measured human breathing patterns when compared to normal breathing. Observed
      changes included an increase in the tidal volume (34%) and period (39%).
      Additionally, the average duty cycle shifted 12% towards a more symmetrical
      breath due to the unequal increase in the inhalation and exhalation times (55%
      and 28%, respectively). The position of the point of maximum flow in each breath
      phase shifted towards the beginning and end of the breath for the inhale and
      exhale by 28% and 48%, respectively. The bench testing revealed that breathing
      pattern shape variation caused statistically significant differences in nebulizer
      output only in two cases. Decreasing duty cycles and shifting the point of
      maximum flow towards the beginning of the breath both result in a decrease in
      output efficiency. Square flow patterns produced slight but consistently higher
      output efficiencies (average 2.1% higher) and a constant output particle size
      over the course of each breath, different from the other non-square patterns.
      Numerical simulations revealed no significant dosage differences resulting from
      breathing pattern shape variations. However, square wave patterns consistently
      produced slight overpredictions in comparison with real nebulizer patterns. In
      contrast, sine wave patterns were found to produce essentially the same results
      as nebulizer patterns in both the bench tests and in the deposition simulations.
      This suggests that sine wave shapes are preferable for simulating breathing when
      bench testing drug delivery using vented jet nebulizers.

PMID- 14572329
TI  - [Diagnosis and treatment of hepatorenal syndrome].

PMID- 14572330
TI  - [Tumor necrosis factor-alpha enhances the effect of endothelin on renal
      vasoconstriction in isolated perfused rat kidney].
AB  - OBJECTIVE: To explore the role of tumor necrosis factor-alpha (TNF-alpha) in the
      pathogenesis of hepatorenal syndrome. METHODS: By isolated perfused kidney
      technique, rat kidneys were perfused at a constant flow. Changes in perfusion
      pressure (mmHg) were consecutively measured with multi-functional physiology
      recorder. After TNF-alpha or heparin treated 90 minutes, the perfusion pressure
      stimulated by endothelin-1 (ET-1) was detected. RESULTS: TNF-alpha and heparin
      didn't modify the baseline perfusion pressure. When ET-1 was added at 2 nmol/L,
      the perfusion pressures increased to (47+/-9) mmHg, (97+/-36) mm Hg and (11+/-6)
      mm Hg in control, TNF-alpha and heparin (10mg/L) treated group, respectively,
      which were different among the three groups (t>or=3.811, P<0.01). No pathological
      damages were found in kidney tissues from all the groups after being stained with
      hematoxylin/eosin. CONCLUSION: TNF-alpha plays an important role in the
      pathogenesis of hepatorenal syndrome by promoting renal vasoconstriction.

PMID- 14572331
TI  - [Cox regression analysis of predictive factors of hepatorenal syndrome].
AB  - OBJECTIVE: To investigate the predictive factors and the best prognostic
      parameter of hepatorenal syndrome (HRS). METHODS: 71 patients with cirrhosis who
      underwent HRS were included for multivariate Cox regression analysis. 35 possible
      predictive factors that included clinical and biochemical features contributing
      to the survival of these patients were analyzed. RESULTS: Only Child-Pugh's score
      at the time of diagnosis was the only dependent risk factor of HRS, RR=1.333, 95%
      CI (1.026, 1.731). CONCLUSION: Child-Pugh's score at the time of diagnosis of HRS
      is the best parameter for predicting the clinical outcome of HRS.

PMID- 14572332
TI  - [Dendritic cells originated from the peripheral blood in chronic hepatitis B
      patients can induce specific T cell immune response].
AB  - OBJECTIVE: To study whether dendritic cells (DCs) derived from the peripheral
      blood in chronic hepatitis B patients can induce specific T cell immune response.
      METHODS: (1)The subjects were divided into 3 groups: chronic hepatitis B group
      (CHB), acute hepatitis B group (AHB), and normal donor group (ND). The peripheral
      blood mononuclear cells (PBMCs) isolated from those subjects were stimulated with
      HBcAg 18 to 27 CTL epitope peptide, and intracellular cytokine staining (ICCS)
      was used for detecting IFN-gamma, IL-2 and TNF-alpha produced by CD8+ T cell. (2)
      DCs generated from PBMCs were pulsed with HBcAg 18 to 27 CTL epitope peptide,
      then were cocultured with autologous lymphocytes for 10 days to induce antigen
      specific T cell, which was assessed by ICCS and cytotoxic assay. RESULTS: (1) The
      memory effect of the PBMCs from AHB group to HBcAg 18 to 27 CTL epitope peptide
      was stronger than that from CHB or ND group (t=2.508-3.305, P<0.05). (2)After
      lymphocytes were cocultured with DC treated with HBcAg 18 to 27 CTL epitope
      peptide, antigen-specific T cell effect was induced. And the killing rates were
      (57.0+/-23.0)%, (49.5+/-20.2)%, (21.8+/-12.9)% at the effector/target of 30:1,
      10:1, 3:1, which were higher than that in control group. CONCLUSIONS: The memory
      T cells against HBV antigen lacks in CHB patients. DCs from CHB patients pulsed
      with HBcAg 18 to 27 epitope peptide can induce HBV antigen-specific T cell, which
      can kill specific target cells and produce cytokines involved in virus clearance.

PMID- 14572334
TI  - [Influence of curative effect on severe hepatitis patients with different plasma
      exchange volume].

PMID- 14572333
TI  - [A new method for amplification and sequence analysis of the full-length of HBV
      genome].
AB  - OBJECTIVES: To develop a new method for amplifying and sequencing the full-length
      of HBV genome. METHODS: A pair of primers located at the nick region of HBV
      molecule and a thermostable polymerase with high fidelity and sensitivity were
      used. After cloning the PCR products into a plasmid, the sequences of HBV genome
      were analyzed. RESULTS: The full-length of HBV genome were acquired using this
      method. The sensitivity and fidelity of the new method were also analyzed. The
      least quantity of initial templates was 10(2) and the artificial mutation rate
      was 1.2 bp/kb. CONCLUSION: This method can be used in amplification and sequence
      analysis of the full-length of HBV genome on a large scale.

PMID- 14572335
TI  - [The role of hepatic sinusoid capillarization during the formation of portal
      hypertension in fibrotic rats induced by dimethylnitrosamine].
AB  - OBJECTIVES: To study the role of hepatic sinusoid capillarization during the
      formation of portal hypertension in fibrotic rats induced by dimethylnitrosamine
      (DMN). METHODS: Hepatic fibrotic rats were induced by administration of DMN
      intraperitoneally three times a week for 4 weeks. The rats were harvested on day
      2 and weeks 1, 2, 3, 4, 5, 6, 8, 12 and 24. The formation of liver fibrosis and
      hepatic sinusoid capillarization were observed by morphologic methods. Pressure
      of portal vein (Ppv) was directed measured with intubation tube method by
      mesentry anterior vein. RESULTS: The Ppv was getting higher and higher with the
      administration of DMN. After four weeks, the Ppv was higher than that of control
      [(1.10+/-0.18)kPa vs (0.52+/-0.04)kPa, t=6.41, P<0.01]. The dynamic change of
      hepatic sinusoid capillarization was in accordance with that of Ppv, which
      normalized gradually after the DMN was stopped. Significant positive correlation
      existed between the dynamic change of Ppv and the expression of vWF, laminin and
      alpha-SMA in sinus (r=0.833, P<0.01; r=0.953, P<0.01; r=0.919, P<0.01).
      CONCLUSION: Hepatic sinusoid capillarization is the vital cause for portal
      hypertension in fibrotic rats induced by DMN.

PMID- 14572336
TI  - [Expression and location of heme oxygenase in the lung of experimental cirrhotic
      rats].
AB  - OBJECTIVES: To observe the function of heme oxygenase (HO) in the lung damage in
      hepatic cirrhosis rats. METHODS: Liver cirrhosis model rats were made by CCl4.
      Lung samples taken from normal and cirrhotic rats were examined for HO-1 and HO-2
      protein and expression distribution with immunohistochemical staining and western
      blot. RESULTS: Liver cirrhosis model rats were successfully constructed. There
      was a notable increase of HO-1 staining (0.062+/-0.021 vs 0.185+/-0.044, t=11.24,
      P<0.01) and protein expression (0 vs 5294.92+/-46.02, t=11.45, P<0.01) in both
      vascular and bronchial smooth muscle cells and endothelium in cirrhotic rats,
      however, no statistical difference of HO-2 between cirrhotic and normal rats was
      observed. CONCLUSION: The HO-CO pathway is probably involved in the pathogenesis
      of lung damage in hepatic cirrhosis rats.

PMID- 14572337
TI  - [Cloning and expressing the E2 subunit of pyruvate dehydrogenase complex].
AB  - OBJECTIVES: To construct the expression vector of the pyruvate dehydrogenase
      complex E2 subunit gene (PDC-E2). METHODS: The PDC-E2 gene was amplified from
      human lymphocytes with RT-PCR, and was cloned into pExSecI vector to induce the
      PDC-E2 expression. The products were identified with western blot and ELISA.
      RESULTS: The expression vector pExSecI/PDC-E2 was successfully constructed. The
      products could be identified by the specific self-antibodies in the sera from the
      primary biliary cirrhosis patients. CONCLUSION: High efficient expression vector
      of PDC-E2 lays the foundation for serum assay of primary biliary cirrhosis
      patients with prokaryotic expressing PDC-E2.

PMID- 14572338
TI  - [Integrin beta1 mediates hepatocellular carcinoma cells chemotaxis to laminin].
AB  - OBJECTIVE: To study the effects of integrin beta1 on the chemotaxis of
      hepatocellular carcinoma (HCC) cells to laminin (LN). METHODS: A micropipette
      technique was adopted to investigate the effect of integrin beta1 blockade on
      pseudopod protrusion of HCC cells in response to LN stimulation. Chemotactic
      pseudopod protrusion of a HCC cell was evaluated using a dual-pipette set-up, in
      which two pipettes filled with LN solution were positional in close contact with
      the same cell, and pseudopod protrusion into each pipette was viewed dynamically
      and recorded with a tape recorder. The lengths of pseudopods were measured, then
      plotted against time to obtain a pseudopod growth curve. The integrin beta1
      subunit on the surfaces of HCC cells was analyzed by flow cytometry. RESULTS: In
      dual pipette chemotaxis experiment, when the two pipettes were filled with LN
      (50microg/ml, 200microg/ml), pseudopods extended from the HCC cells into each of
      the pipettes nearly symmetrically. Upon addition of anti-CD29 (20microg/ml) to
      one of the pipettes, the pseudopod protrusion was blocked almost completely,
      while the pseudopod protrusion into the opposite pipette became more evidently,
      with larger maximum length. The expression rate of integrin beta1 on the cells
      was up to 95.78%. CONCLUSION: Integrin beta1 subunit is the important receptor
      for mediating HCC cells chemotaxis to laminin.

PMID- 14572339
TI  - [Expression and implication of multidrug resistance associated -protein gene in
      primary hepatocellular carcinoma].
AB  - OBJECTIVES: To investigate the relationship between the expression of mrp and
      both the responses to chemotherapy and the level of alpha-fetoprotein (AFP).
      METHODS: S-P immunohistochemical staining and in situ PCR were adopted to detect
      MRP and mRNA mrp in 54 cancer tissues taken from untreated HCC patients whose
      tumor could not be removed during the operation, 24 para-cancer tissues, and 12
      posthepatitis cirrhosis paraffin-embedded tissues. The relationship between the
      expression of mrp and their curative effect to chemotherapy in all the patients
      was analyzed, so was the relationship between the expression of mrp and the level
      of AFP in 38 patients whose AFP was positive after operation. RESULTS: The
      positive rates of expressing MRP and mRNA mrp in the three kinds of tissues were
      61.1%, 25.0%, 33.3% and 77.8%, 37.5%, 41.7%, respectively, with higher rates in
      HCC tissues than those in other tissues (chi2=9.842, P< 0.01; chi2=13.956,
      P<0.01). The rates of curative effect to chemotherapy in groups of negative and
      positive MRP and mRNA mrp expression were 61.9%, 30.3% and 75.0%, 33.3%,
      respectively, with significant difference between the negative and positive
      groups (chi2=5.242, P<0.05; chi2=6.627, P< 0.05). As the same as the percentage
      of curative effect to chemotherapy, the rates of AFP level decreased evidently
      were 62.5%, 27.3% and 87.5%, 30.0%, with remarkable difference between the two
      groups (chi2=4.710, P<0.05; chi2=8.566, P<0.05). CONCLUSIONS: The multidrug
      resistance (MDR) of HCC is related to mrp expression, which initiates the
      intrinsic MDR. There is an important significance by detecting mrp expression in
      selecting chemotherapeutic method, and the expression of mrp can act as an
      indicator for chemotherapeutic sensitivity in HCC patients.

PMID- 14572340
TI  - [Inhibitory effects of antisense focal adhesion kinase oligodeoxynucleotides on
      the invasion of Bel 7402 hepatocellular carcinoma cells].
AB  - OBJECTIVE: To study the inhibitory effects of antisense focal adhesion kinase
      (FAK) oligodeoxynucleotides (ODN) on the invasion of Bel 7402 cells, and
      investigate the mechanisms. METHODS: LipofecTAMINE-mediated antisense FAK ODN was
      transfected into Bel 7402 cells. Cell number and viability were evaluated every
      24 hours by trypan blue dye exclusion. Cell attachment assay was carried out at
      intended time points in a microculture well pre-coated with fibronectin (FN). The
      invasive activity of tumor cells was assayed in a transwell cell culture chamber.
      Cell cycle and cell apoptosis analysis were performed with flow cytometry (FCM).
      RESULTS: The expression of p125FAK in the group treated with antisense FAK ODN
      (6.49%+/-0.10%) significantly decreased, compared with those in the group treated
      with sense FAK ODN (14.33%+/-1.88%) and control group (16.68%+/-1.62%), F=7.66,
      P<0.01. Antisense FAK ODN significantly inhibited the growth of Bel 7402 cells by
      30%-60%, the attachment by 25%-55%, and the invasion, 15%-25%. The decreased
      expression of FAK in Bel 7402 cells caused a G2/M cell cycle arrest, and the
      cells at S phase decreased significantly. The occurrence of apoptosis detected by
      FCM increased significantly in the group treated with antisense FAK ODN.
      CONCLUSIONS: Inhibition of FAK expression significantly decreases the attachment
      between ECM and Bel 7402 cells, and the ability of Bel 7402 cells to invade the
      reconstituted basement membrane. In addition, FAK suppression significantly
      inhibits the proliferation of Bel 7402 cells in vitro, and increases their
      apoptosis.

PMID- 14572341
TI  - [Detection and analysis of the new kind of G743C and G743A point mutation of HBV
      P gene in hepatitis B virus infected patients resistant to lamivudine].
AB  - OBJECTIVE: To explore the point mutation in hepatitis B virus polymerase (HBV P)
      gene in HBV-infected patients resistant to lamivudine. METHODS: HBV P gene was
      amplified by PCR and the products was sequenced to analyze the YMDD mutation.
      Then the variants were detected by polymerase chain reaction-restriction fragment
      length polymorphism (PCR-RFLP) with the following restriction enzymes: Fok I, Ssp
      I, Alw441 and were separated by 8.0% polyacrylamide gel electrophoresis. RESULTS:
      Comparing with the sequences of standard HBV genome, there were 16 patients with
      G743C mutation and 1 patient with G743A mutation, and the codon ATG turned to ATC
      and ATA, YMDD motif changed into YIDD. But this kind of YIDD mutation was not
      proved by PCR-RFLP assay in the 17 patients. CONCLUSIONS: The G743C and G743A
      mutations in HBV P gene, resulting in YMDD motif changed into YIDD, are detected
      only by direct sequencing, not by PCR-RFLP. The new kind of G743C and G743A point
      mutations in HBV P gene is important for the detection of HBV P gene YMDD
      mutation.

PMID- 14572342
TI  - [Changes of IL-12 in the sera of chronic hepatitis B patients before and after
      lamivudine treatment].

PMID- 14572344
TI  - [Influence of interferon alpha on the serum fibrosis markers of chronic hepatitis
      C patients].

PMID- 14572343
TI  - [Effects of HCV genotypes and HLA-DRB alleles on the response of chronic
      hepatitis C patients to interferon alpha and libavilin].
AB  - OBJECTIVES: To study the effects of HCV genotypes and HLA-DRB alleles on the
      response of chronic hepatitis C patients to interferon alpha and libavilin.
      METHODS: Genotypes of HCV in 113 patients with HCV infection treated with
      interferon alpha and libavilin were investigated. Gene chips were used to analyze
      the frequency of HLA-DRB alleles in 25 patients of them. The response to
      interferon alpha and libavilin therapy were discussed. RESULTS: The response
      rates in the four HCV types were different, HCV-IV/2b the highest (57.78%), HCV
      I/1a and -III/2a lower (46.15% and 47.62%), and HCV-II/1b the lowest (11.76%).
      The response rate to IFN and libavilin therapy in patients with DRB1*07 positive
      was higher, while in patients with DRB1*04 positive was lower. Sex, HCV genotypes
      and HLA-DRB alleles were all related to the response. Female, patients with HCV
      IV/2b and HLA-DRB1*07 presented almost complete response, but male, patients with
      HCV-II/1b and HLA-DRB1*04 usually appeared non-response. DRB1*07 allele and HCV
      IV/2b were the closest factors related to the response. CONCLUSIONS: Not only
      virus but also host playes an important role in the curative effect of anti-virus
      therapy. It is necessary to view from the angle of host, adjusting the host's
      immune status to accelerate the clearance of HCV.

PMID- 14572346
TI  - [Acute severe hepatitis and hemolytic anemia appeared firstly in a Wilson's
      disease patient].

PMID- 14572347
TI  - [Pathogenesis of hepatorenal syndrome].

PMID- 14572345
TI  - [Investigation on the influence of alcohol on chronic hepatitis C patients].

PMID- 14572348
TI  - [Therapy for hepatorenal syndrome].

PMID- 14572349
TI  - [Clinical analysis of 38 patients with hepatorenal syndrome].

PMID- 14572350
TI  - [Improvement of molecular adsorbent recirculating system on chronic severe
      hepatitis patients with multiple organ failure].

PMID- 14572351
TI  - [Detecting the gamma-glutamyltransferase mRNA-H in the peripheral blood of
      primary hepatocellular carcinoma patients].

PMID- 14572352
TI  - [Value of detecting HBV DNA with nested-PCR in the sera from patients with anti
      HBs positive].

PMID- 14572353
TI  - [Effects of interferon-alpha on the apoptosis and gene expression of hepatic
      stellate cells].

PMID- 14572354
TI  - [Effects of the tyrosine protein kinase inhibitor, genistein on the filamentous
      actin and cytosolic calcium in rat hepatic stellate cells].

PMID- 14572356
TI  - [Effects of Interleukin-10 on the proliferation and Fas/Fas ligand expression of
      hepatic stellate cells].

PMID- 14572355
TI  - [Relationship among Ki-67, bcl-2 and the expression of survivin in hepatocellular
      carcinoma].

PMID- 14572357
TI  - [Current treatments for hepatorenal syndrome].

PMID- 14572358
TI  - Endothelin converting enzyme (ECE) activity in normal pregnancy and preeclampsia.
AB  - OBJECTIVE: Enhanced production of endothelin-1, due to endothelial cell
      dysfunction has been considered to be the cause of increased plasma levels of
      endothelin-1 in preeclampsia. The present study was aimed at analyzing endothelin
      converting-enzyme activity, (which reflect the production rate of endothelin-1
      (ET-1) from big endothelin-1 (big ET-1)), big endothelin-1, and endothelin-1
      concentrations from women with preeclampsia compared to normal pregnant women.
      Moreover, we analyzed plasma levels of these substances longitudinally throughout
      normal pregnancy. STUDY DESIGN: Twenty-nine pregnant healthy women were recruited
      to the study. Blood samples were obtained at 18, 28, and 38 weeks gestation and
      six weeks postpartum. Twenty-seven women with preeclampsia were included. Blood
      samples were taken at diagnosis (average 35 weeks gestation; range 27-39 weeks)
      and six weeks postpartum. Endothelin-1 was analyzed by enzyme linked immunoassay
      (ELISA) and big-ET-1 by radioimmunoassay (RIA). Endothelin-converting-enzyme
      activity was measured using big endothelin-1 as a substrate and thiorphan as an
      inhibitor of serum neutral endopeptidase. The amount of endothelin-1 generated
      during one hour was measured by RIA. Mean +/- SEM is given. RESULTS: In normal
      pregnancy endothelin-1 concentrations at 38 weeks and postpartum were increased
      by 30% (p < 0.01) and 50% (p < 0.001), respectively compared with the second
      trimester values. Endothelin-converting-enzyme activity did not change. At
      diagnosis endothelin-1 was higher in women with preeclampsia than in the controls
      at 38 weeks (0.96 +/- 0.07 vs. 0.64 +/- 0.06 pmol/L; p < 0.001). Likewise,
      endothelin-converting-enzyme activity was higher in the preeclampsia group (222
      +/- 15 vs. 172 +/- 8 pmol ET/ml/h; p < 0.01). This difference remained at six
      weeks postpartum. CONCLUSION: Our findings imply enhanced ET-1 production in
      preeclampsia. The elevated endothelin-converting-enzyme activity postpartum may
      indicate an inherent endothelial dysfunction predisposing to preeclampsia or that
      preeclampsia may cause irreversible changes in endothelial function.

PMID- 14572360
TI  - Pathological uterine perfusion in the second trimester is not associated with
      neutrophil activation.
AB  - OBJECTIVE: Preeclampsia and intrauterine growth retardation (IUGR) are associated
      with elevated concentrations of myeloperoxidase (MPO) and polymorphonuclear (PMN)
      elastase, which indicate maternal neutrophil activation. The aim of the study was
      to measure maternal MPO and PMN elastase plasma concentrations in second
      trimester pregnancies with pathological uterine perfusion that are a high risk
      group for preeclampsia and IUGR, and compare them to normal controls. METHODS:
      The study includes 25 pregnancies with normal and 25 pregnancies with
      pathological uterine perfusion. In both groups, doppler-sonographic measurement
      of uterine perfusion was performed in the twenty-first week of gestation.
      Maternal plasma concentrations of MPO and PMN elastase were measured using a
      specific ELISA for both enzymes. RESULTS: The plasma MPO concentration of
      pregnant women with normal perfusion did not differ significantly from that of
      the group with pathological perfusion (27.4 +/- 3.3 vs. 23.7 +/- 2.0 ng/mL).
      Likewise, the plasma PMN elastase-concentration also did not show a significant
      difference between the groups (5.7 +/- 0.5 ng/mL normal vs. 8.0 +/- 1.0 ng/mL
      pathological). Patients with pathological perfusion that later developed
      preeclampsia or IUGR (9/25) showed unchanged MPO and PMN elastase values in the
      second trimenon compared to those with pathological perfusion and normal outcome.
      CONCLUSIONS: Pathological uterine perfusion in the second trimester was not
      associated with maternal neutrophil activation. The measurement of the MPO and
      PMN elastase concentration suggested that neutrophil activation in preeclampsia
      or IUGR is a secondary effect of the disease rather than a primary
      pathophysiological factor.

PMID- 14572359
TI  - Are gestational and essential hypertension similar? Left ventricular geometry and
      diastolic function.
AB  - OBJECTIVE: To evaluate the differences and similarities in diastolic function and
      left ventricular geometry in gestational and essential hypertension. METHODS:
      Thirty-nine consecutive gestational hypertensive pregnant women in the third
      trimester of gestation (GH), 40 nonpregnant essential hypertensive women (EH),
      and 38 normotensive nonpregnant women (N) matched for age were enrolled into the
      study and underwent echocardiographic and Doppler evaluations. The GH and EH
      patients were evaluated prior to the administration of any drug treatment.
      RESULTS: Left atrial function was similar in GH and N subjects and lower than
      that in EH patients. Both GH and EH patients had early left ventricular diastolic
      filling pattern significantly different as compared to N subjects (longer
      isovolumetric relaxation time, deceleration time of the E wave, and lower E wave
      velocity in GH and EH vs. N), whereas the late filling properties were similar in
      GH and N subjects with a lower A velocity, and velocity-time integral vs. EH (p <
      0.05). Systolic fraction of the pulmonary vein flow was similar in GH and EH
      patients and lower in N subjects. Altered left ventricular geometry was more
      common in GH than in EH, whereas normotensive subjects did not show any
      alteration of the geometric pattern. CONCLUSIONS: Gestational and essential
      hypertension induce similar early altered diastolic filling of the left
      ventricle. Essential hypertension is characterized by a compensatory late filling
      mechanism due to an enhancement of left atrial function. Gestational hypertension
      is characterized by altered left ventricular geometry, which is far less common
      during essential hypertension.

PMID- 14572361
TI  - Calcium-ATPase activity of red blood cell ghosts from preeclamptic women,
      antepartum and postpartum.
AB  - OBJECTIVE: We determined the calcium activated adenosine triphosphatase (Ca
      ATPase) activity and level of lipid peroxidation thiobarbituric acid-reactive
      substances (TBARS) of red blood cell ghosts in the antepartum and postpartum of
      normotensive and preeclamptic pregnant women. METHODS: Samples of venous blood
      were obtained by venipuncture of nulliparous normotensive and preeclamptic
      pregnant women antepartum and two, four, six, and 20 weeks postpartum. The red
      blood cell ghosts were prepared and assayed for Ca-ATPase activity and TBARS.
      MAIN OUTCOME MEASURE(S): We expected to find a return to normal values of both Ca
      ATPase activity and TBARS level of the red blood cell ghosts, modified in the
      preeclamptic pregnant women, during their puerperium. RESULTS: The Ca-ATPase
      activity of red cell ghosts from preeclamptic women, antepartum, is lower than
      that of normotensive pregnant women. The ATPase activity returns to normal values
      during the first six weeks of postpartum. The level of TBARS of red cell ghosts
      from preeclamptic women follows a pattern that is inversely proportional to the
      one of the Ca-ATPase activity. CONCLUSIONS: Preeclampsia produces a significant
      diminution of the Ca-ATPase activity and an increase in the levels of TBARS in
      the erythrocytes. As soon as all the symptoms of preeclampsia disappear in the
      postpartum, both Ca-ATPase activity and TBARS return to normal values.

PMID- 14572362
TI  - The use of standard dose of magnesium sulphate in prophylaxis of eclamptic
      seizures: do body mass index alterations have any effect on success?
AB  - OBJECTIVE: We anticipated that the universal use of a standard magnesium sulfate
      infusion to prevent eclamptic convulsions in preeclamptic patients would result
      in alterations in circulating magnesium levels that were negatively correlated
      with the patient's body mass index. We postulated that the highest failure rate
      with seizure prophylaxis would occur in patients with the highest body mass
      index. MATERIALS AND METHODS: After discarding 6 patients, this study was
      performed in 194 of 200 preeclamptic patients admitted to our high risk pregnancy
      unit between February 2000 and August 2000, who were divided into four groups
      determined by body mass indices. A standard magnesium sulfate infusion protocol
      (loading dose 4.5 g/15 minutes followed by 1.8 g/hour) was administered to 194
      preeclamptic patients. One hundred and thirty-eight severe preeclamptic patients
      received magnesium sulfate during both antepartum and postpartum periods. The
      remaining 56 patients only received the therapy during the postpartum period.
      Serial serum magnesium levels of each groups were recorded and compared. RESULTS:
      The 1.8 g infusion rate produced acceptable magnesium levels in the majority of
      patients but most were in the lower 50% of the therapeutic range. Levels were
      lowest in patients with high body mass indices (this group recorded most of the
      subtherapeutic levels, particularly when patient were infused antepartum). Apart
      from 13 referred patients who had convulsed prior to admission no eclampsia
      occurred during the antepartum period while seizures occurred in nine women
      during the postpartum period. Two hours after the initiation of the therapy,
      magnesium levels were inversely related to the body mass index (BMI) both during
      the ante- and postpartum periods (Prepartum; group I: 5.97 mg/dl, group II: 4.90
      mg/dl, group III: 4.35 mg/dl, group IV: 3.88 mg/dl; Postpartum; group I: 5.89
      mg/dl, group II: 5.71 mg/dl, group III: 4.82 mg/dl and group IV: 4.61 mg/dl,
      Table 4). Although the lowest levels were detected in patients with high body
      mass indices, in contrast to our hypothesis, eclamptic seizures occurred in four
      patients with low body mass indices. Furthermore therapeutic serum magnesium
      levels were detected in three of these patients. There was no association between
      treatment failures and body mass or with magnesium levels. CONCLUSION: The
      infusion regimen described herein resulted in therapeutic levels in the majority
      of patients that correlated inversely with body mass index. However most levels
      fell within the lower range of what many studies consider "therapeutic"
      suggesting that maintenance infusion rates of at least 2-2.5 g/hour would be more
      appropriate. This would be particularly true in patients with body mass indices
      exceeding 30, where subtherapeutic levels occurred most frequently. The study's
      limited power prevents conclusions on outcomes but what is of interest is that
      eclamptic convulsions did not correlate with either body mass index or
      circulating plasma magnesium levels.

PMID- 14572363
TI  - Insulin-induced hypertension, L-arginine, and endothelial nitric oxide synthase
      in pregnant rats.
AB  - Pregnancy-induced hypertension in rats with chronic exogenous hyperinsulinemia is
      associated with reduced urinary excretion of nitric oxide metabolites. We tested
      the hypothesis that there are perturbations of endothelial nitric oxide synthase
      in their kidneys. We studied three groups of rats: control pregnant rats (n = 6);
      pregnant rats with hyperinsulinemia by subcutaneous sustained-release insulin
      pellet (n = 5); and hyperinsulinemic pregnant rats treated with l-arginine 2 gL
      in drinking water (n = 5). By the end of pregnancy blood pressure was 78 +/- 12
      mm Hg in controls, 119 +/- 15 mm Hg in hyperinsulinemic rats, and 77 +/- 8 mm Hg
      in l-arginine-treated hyperinsulinemic rats, p < 0.007. Serum creatinine was 0.4
      mg/dl in controls, 0.6 mg/dl in hyperinsulinemic rats, and 0.5 mg/dl in l
      arginine-treated rats, p < 0.05. Corresponding urinary excretion of nitric oxide
      metabolites was 2.1 +/- 0.5, 1.2 +/- 0.2, and 1.5 +/- 0.2 micromols/mg
      creatinine, p < 0.01. Expression of endothelial nitric oxide synthase protein in
      kidneys by Western blot was not different between controls and hyperinsulinemic
      rats, 5.6 +/- 2.4 and 5.8 +/- 3.4 OD x mm2, but was nearly doubled in l-arginine
      treated rats, 10.8 +/- 2.3, p < 0.03. Thus, the salutary effect of l-arginine on
      hyperinsulinemic pregnancy-induced hypertension (PIH) may be mediated, in part,
      by endothelial nitric oxide synthase in their kidneys.

PMID- 14572364
TI  - Increase in systolic blood pressure of > or = 30 mm Hg and/or diastolic blood
      pressure of > or = 15 mm Hg during pregnancy: is it pathologic?
AB  - OBJECTIVE: To determine whether a rise in systolic blood pressure (SBP) > or = 30
      mm Hg and/or diastolic blood pressure (DBP) > or = 15 mm Hg in the absence of
      hypertension during pregnancy is associated with adverse pregnancy outcomes.
      METHOD: We conducted a retrospective, longitudinal study of 1,498 pregnant women
      without hypertension or proteinuria in the first trimester. The blood pressure
      levels measured during the first (7.8 +/- 2.3 weeks), second (20.7 +/- 1.2
      weeks), and third trimesters (38.6 +/- 1.5 weeks) were analyzed. The perinatal
      outcome was compared between women who exhibited a rise in SBP > or = 30 mm Hg
      and/or DBP > or = 15 mm Hg during pregnancy (large Delta BP group) and women who
      did not (small Delta BP group) using one way analysis of variance, chi-square
      test, or Fisher's exact test. The contribution of gestational hypertension and a
      large Delta BP to the development of adverse pregnancy outcomes was evaluated
      using multivariate logistic regression analysis. RESULTS: Of 1441 women who
      remained normotensive (SBP < 140 mm Hg and DBP < 90 mm Hg) during pregnancy, 238
      (16.5%) and 1,203 (83.5%) belonged to the large Delta BP and small Delta BP
      groups, respectively. There were no significant differences between the two
      groups in the occurrence rate of gestational proteinuria, preterm deliveries, low
      birth-weight infants, or small-for-gestational age infants. A large Delta BP was
      not a risk factor in itself for the occurrence of gestational proteinuria or
      small-for-gestational age infants after controlling for the effect of gestational
      hypertension. CONCLUSION: A rise in SBP > or = 30 mm Hg and/or DBP > or = 15 mm
      Hg is not a risk factor of adverse outcome among women who remain normotensive
      during pregnancy.

PMID- 14572365
TI  - The importance of parity to major maternal morbidity in the eclamptic mother with
      HELLP syndrome.
AB  - OBJECTIVE: To determine if the rate of major morbidity from severe preeclampsia
      with/without hemolysis, elevated liver enzymes, and low platelets (HELLP)
      syndrome differs by parity. METHODS: Retrospective investigation of 970 gravidas
      with severe preeclampsia with and without HELLP syndrome analyzed according to
      parity. RESULTS: Altogether 609 (63%) patients were nulliparous and 361 (37%)
      parous. Between groups there was no significant difference in the incidence of
      overall major morbidity (21% vs. 19%, p=0.467), or specific morbidities including
      hematologic/coagulopathic (13.6% vs. 11.9%, p=0.442), cardiopulmonary (8.9% vs.
      7.2%, p=0.362), CNS/visual (1.8% vs. 2.8%, p=0.319), or hepatorenal (0.8% vs.
      2.2%, p=0.068). Although eclampsia was significantly more common in nulliparous
      (10.2%) than in parous patients (5.5%, p=0.012), the later significantly more
      often demonstrated major maternal morbidity associated with eclampsia (50%) than
      did nulliparous patients (25%, p=0.043). CONCLUSIONS: Unless parous patients with
      severe preeclampsia with or without HELLP syndrome develop eclampsia, their
      disease acuity does not differ significantly from their nulliparous counterparts.

PMID- 14572366
TI  - Preeclampsia and calcium-ATPase activity of plasma membranes from human
      myometrium and placental trophoblast.
AB  - OBJECTIVE: We determined calcium-activated adenosine triphosphatase (Ca-ATPase)
      activity and thiobarbituric acid-reactive substances (TBARS) of plasma membranes
      from myometrium and placental trophoblast of normotensive and preeclamptic
      pregnant women. METHODS: Samples of myometrium were obtained by uterine biopsies
      taken upon delivery by cesarean section from nulliparous normotensive and
      preeclamptic pregnant women. Placentas were obtained after full term vaginal
      delivery from either normotensive or preeclamptic women. Plasma membrane
      fractions were prepared from both myometrium and placenta and assayed for Ca
      ATPase activity and TBARS. MAIN OUTCOME MEASURE(S): We expected to find a higher
      level of TBARS and, consequently, a lower activity of Ca-ATPase of the plasma
      membrane fractions obtained from both myometrium and placenta of preeclamptic
      women. RESULTS: The Ca-ATPase activity of myometrium and placental trophoblast
      from preeclamptic women was about 50% lower than that from normotensive women,
      while the TBARS were higher. CONCLUSIONS: A reduced Ca-ATPase activity, caused by
      an increased level of TBARS, may result in an increase in the cytosolic calcium
      concentration in the vascular smooth muscle cells of preeclamptic women and thus
      partially explain the high blood pressure developed by these patients.

PMID- 14572367
TI  - [Contribution of high risk human papillomavirus testing to the management of
      premalignant and malignant lesions of the uterine cervix].
AB  - BACKGROUND AND OBJECTIVE: High risk human papillomaviruses (HR-HPV) are
      consistently associated with premalignant and malignant lesions of the uterine
      cervix. Thus, the use of molecular techniques to detect HPV has been proposed to
      improve the results of conventional diagnostic strategies. In the present study,
      we evaluated the usefulness of the detection of HR-HPV in a cervical pathology
      unit. PATIENTS AND METHOD: 1005 women (mean age [SD], 38.4 [12.3]; range, 16-83)
      were referred for a cytology of atypical cells of unknown origin (ASCUS),
      squamous intraepithelial lesion (SIL) or carcinoma in the six months previous to
      the admission. All patients underwent a colposcopy, Pap test and/or histological
      study as well as HR-HPV detection using the Hybrid Capture II test. RESULTS: HR
      HPV was detected in 96% high grade-SIL, 86% carcinomas of the uterine cervix and
      86% low grade-SIL, but only in 25% women with no cervical lesions and 0% women
      with metastatic carcinomas to the cervix (p<0.001). The sensitivity of this test
      for high grade-SIL or higher was 90.2% and the negative predictive value was
      96.5% (odds ratio=18.9; 95% confidence interval, 10.9-33.1). In patients with
      ASCUS, a negative result for HR-HPV nearly excluded the presence of a cervical
      lesion (negative predictive value, 98.52%). CONCLUSIONS: HR-HPV detection using
      Hybrid Capture II is useful in the study of lesions of the uterine cervix. It
      displays a high sensitivity for the diagnosis of squamous intraepithelial lesions
      and invasive carcinomas and a high usefulness in the management of ASCUS cases.

PMID- 14572368
TI  - [Non mydriatic retinal camera: cost-effectiveness study for early detection of
      diabetic retinopathy].
AB  - BACKGROUND AND OBJECTIVE: Cost-effectiveness analysis (ACE) for application of
      fundoscopic photograph with non mydriatic retinal camera (Ffo-CNM) in early
      diagnostic of diabetic retinopathy (RD) compared with ophthalmoscopic view by
      pupillary dilation. PATIENTS AND METHOD: diabetic patients, older than 14 years,
      attended on three Health Primary Care Areas (n=1495). Effectiveness measurement:
      predictive value of a positive test (VPD) and correctly diagnosed cases. Cost
      measurement: total cost by patient. ACE: defined as expected cost by VPD case and
      as expected cost by correctly diagnosed case. The results were submitted to an
      analysis of sensitivity for the study main variables. RESULTS: Ffo-CNM presented
      90.91% of sensitivity [95% CI, 69.4-98.4%], 78.21% of specificity [95% CI, 67.1
      86.4%], 54.05% positive predictive value [95% CI, 37.1-70.2%] and 96.83% of
      negative predictive value [95% CI, 88-99.4%]. Effectiveness, defined as VPD case,
      was 15.4% for ophthalmoscopic view and 19.5% for Ffo-CNM, and defined as
      correctly diagnosed case, was 70% and 79.8%, respectively. Cost-effectiveness
      ratio: a) for health care system, the cost by VPD case was 52.62 euros for
      ophthalmoscopic view and 28.44 euros for Ffo-CNM and cost by correctly diagnosed
      case was 11.58 euros and 6.95 euros, respectively, and b) for the society, cost
      by VPD case was 100.13 euros for ophtalmoscopic view and 34.54 for Ffo-CNM and
      the cost by correctly diagnosed case was 22.03 euros and 8.44 euros respectively.
      CONCLUSIONS: If an introduction of a early detection of RD program for the entire
      diabetic population was decided the option to make it using Ffo-CNM would be the
      most efficient.

PMID- 14572369
TI  - [Sentinel node biopsy in patients with oral cancer: a pilot study].
AB  - BACKGROUND AND OBJECTIVE: Sentinel node (SN) biopsy represents an alternative to
      full lymph node dissection in the surgical treatment of several malignant tumors.
      PATIENTS AND METHOD: Prospective study of 32 consecutive patients with clinically
      node-negative oral cancer comparing SN biopsy results with standard neck
      dissection. RESULTS: An effective SN localization was achieved in 31 patients
      (97%) and a complete agreement with neck dissection was observed: 16 were true
      negative and 15 were true positive. In 11 out of the 15 positive cases, the SN
      was the only node containing metastasis (73%). CONCLUSION: SN biopsy predicts the
      subclinical lymph node status in oral cancer patients.

PMID- 14572370
TI  - [Value of human papilloma virus testing in the diagnosis and screening of
      cervical neoplasia].

PMID- 14572371
TI  - [Cancer drug prevention].

PMID- 14572372
TI  - [Antiphospholipid syndrome updating].
AB  - The antiphospholipid syndrome (APS) was defined 20 years ago by Hughes as a
      thrombosis (arterial and/or venous) state and/or recurrent pregnancy loss in the
      presence of antiphospholipid antibodies like lupic anticoagulant and/or
      anticardiolipin, which sometimes coexist with thrombocytopenia. Although the
      prevalence of APS is estimated to be 3 to 200 cases per 100,000 inhabitants, many
      cases remain without a proper diagnosis. Recurrent thrombosis events can happen
      at any site in the vascular tree, yet most common affected sites are deep veins
      and cerebral arteries. As a result of its vast and protean manifestations, APS is
      currently being dealt with by most medical specialties. But despite research
      advances and improvements in its knowledge, many features of this syndrome such
      as its etiology and pathophysiology are not well understood yet. Standard therapy
      for vascular and obstetric problems is difficult because of the absence of
      evidence-based guidance and continues to be based on antiplatelet and
      anticoagulation drugs. Yet some authors claim individual treatments according to
      the risk of thrombosis or fetal loss. In this review we offer, through an
      extensive bibliographical search of the subject over the last 2 years, a view of
      the state-of-the-art of APS including current criteria for diagnosis, molecular
      basis, main associated clinical manifestations, management and treatment.

PMID- 14572373
TI  - [A physician in the tropics].

PMID- 14572374
TI  - [Myocarditis as an onset form of varicella].

PMID- 14572375
TI  - [Transfusion in elderly patients with hip fracture: can it be avoided?].

PMID- 14572377
TI  - [Are molecular techniques useful in aspergillosis surveillance and control?].

PMID- 14572378
TI  - Combined used of RAPD and touchdown PCR for epidemiological studies of
      Aspergillus fumigatus.
AB  - INTRODUCTION: Aspergillus fumigatus is a filamentous fungus that acts as an
      opportunistic pathogen and has emerged as a major problem in immunosuppressed
      patients. Nosocomial outbreaks of aspergillosis are becoming more frequent, but
      their identification and epidemiological characterization is slow and difficult.
      OBJECTIVE: Description of a fast, sensitive, specific method to identify and
      fingerprint A. fumigatus using methodology available in clinical laboratories.
      METHODS: We studied several strains of A. fumigatus isolated from patients with
      invasive aspergillosis (n = 4), the hospital environment (n = 5) and reference
      cultures (n = 1), as well as other close phylogenetic fungal species from
      patients (n = 1), hospital environment (n = 6) and reference cultures (n = 1). A.
      fumigatus was identified by both touchdown PCR and conventional phenotyping
      methods. Genotyping was performed with random amplification of polymorphic DNA
      (RAPD) analysis, comparing the results from two primers (OPZ-19 and R-108) and
      different amplification protocols with regard to band resolution and
      reproducibility. RESULTS: Touchdown PCR and phenotype results were identical.
      Best RAPD results were obtained with the R-108 primer and considerably longer
      ramp times between annealing and extension. CONCLUSION: RAPD analysis is a fast,
      reliable tool for DNA fingerprinting. Patterns may be easier to repeat and
      interpret when longer ramp times are used. Touchdown PCR combined with RAPD
      analysis is a sensitive, accurate method for managing clinical outbreaks of
      Aspergillus fumigatus.

PMID- 14572379
TI  - [Epidemiological survey of dermatophytosis in Spain (April-June 2001)].
AB  - INTRODUCTION: A three-month (April-June 2001) cross-sectional study was designed
      to assess the epidemiological profile of dermatophytosis in Spain. METHODS: Sixty
      two medical centers belonging to 14 different autonomous regions of Spain took
      part in the survey. A total of 491 strains were sent the Mycology Unit of the
      National Microbiology Center together with a form containing information on each
      patient. Isolates were identified by routine methods. RESULTS: The average age of
      the patients was 38.7 years and 55.6% were men. The most frequent dermatophytoses
      were tinea unguium (39.1%), tinea corporis (25.1%), tinea pedis (12.6%), and
      tinea capitis (11.2%). Trichophyton rubrum (43%) was the most prevalent species.
      T. mentagrophytes (21.2%) and Microsporum canis (9.8%) were the second and third
      most common species, respectively. Tinea unguium was significantly associated
      with urban residence, and tinea corporis with rural residence and contact with
      animals. T. rubrum was related with urban dermatophytosis and T. mentagrophytes
      with rural cases. Tinea capitis due to T. tonsurans and T. violaceum was related
      with patients of North African origin. Tinea unguium was the most prevalent
      infection by autonomous region, except in Castilla-Leon, Asturias, Andalucia and
      Aragon, where tinea corporis was the most common dermatophytosis. Tinea capitis
      was the most frequent infection in Castilla-La Mancha and Extremadura. T.
      mentagrophytes was more prevalent than T. rubrum in Valencia, Castilla-La Mancha,
      Aragon and Murcia. CONCLUSION: This cross-sectional study shows regional
      differences in the clinical and microbiological features of dermatophytosis in
      Spain. Epidemiological surveys are an essential tool for developing strategies
      for infection control.

PMID- 14572380
TI  - [In vitro activity of voriconazole and three other antifungal agents against
      dermatophytes].
AB  - INTRODUCTION: The increase in infections due to dermatophytes in recent years led
      us to study the effectiveness of new antifungal formulations against these
      microorganisms. METHODS: The in vitro activity of a new antifungal agent,
      voriconazole, was compared with three other antifungal agents, itraconazole,
      fluconazole and terbinafine, against 120 dermatophytes belonging to four species
      (61 Trichophyton mentagrophytes, 34 Microsporum canis, 13 M. gypseum and 12 T.
      rubrum). A broth microdilution method was used following the recommendations of
      the NCCLS document M38-P with some modifications. RESULTS: Terbinafine was the
      most active agent against the dermatophytes studied (MIC90 < or = 0.03 mg/ml),
      followed by voriconazole (MIC90, 0.25 micro g/ml) and itraconazole (MIC90, 0.5
      micro g/ml). Fluconazole was the least active antifungal agent. The most
      susceptible species was M. canis. CONCLUSIONS: Voriconazole was found to have
      effective activity against dermatophytes.

PMID- 14572381
TI  - [Antifungal susceptibility of Candida spp. isolates from blood cultures in a five
      year period (1997-2001)].
AB  - INTRODUCTION: This retrospective study investigates the incidence of candidemia
      and antifungal susceptibility of Candida spp. isolates from blood cultures
      performed in the period from January 1997 to December 2001. METHODS: Amphotericin
      B, fluconazole, itraconazole and flucytosine minimal inhibitory concentrations
      (MICs) were determined using the Sensititre YeastOne broth microdilution assay
      for the 53 isolates detected in the study period: C. parapsilosis (22), C.
      albicans (19), C. glabrata (5), C. krusei (3), C. tropicalis (2) and C.
      guilliermondii (2). RESULTS: The incidence of candidemia was 0.25 episodes per
      1000 admissions in the period studied. C. parapsilosis was present in 41.5% of
      cases, followed by C. albicans (35.8%), C. glabrata (9.4%), C. krusei (5.5%), C.
      tropicalis (3.7%) and C. guilliermondii (3.7%). Isolation of C. parapsilosis was
      significantly associated with the neonatal and pediatric ICU. None of the
      isolates presented an amphotericin B MIC > 1 micro g/ml. All the C. krusei
      isolates were resistant to fluconazole. Itraconazole resistance and dose
      dependent fluconazole susceptibility was found in 80% of C. glabrata isolates.
      Only one C. parapsilosis isolate was resistant to flucytosine. CONCLUSIONS: The
      incidence of candidemia in our hospital was low. C. parapsilosis was the most
      common species and was associated with neonatal and pediatric ICUs. Fluconazole
      and itraconazole resistance was only found among C. krusei and C. glabrata
      isolates, which accounted for 15% of the total Candida spp. isolated from blood
      cultures in our hospital.

PMID- 14572382
TI  - [CHROMAgar Candida with fluconazole: comparison with microdilution techniques].
AB  - INTRODUCTION: The increasing incidence of fungal infections and the reported
      emergence of resistance to antifungal agents call for the development of
      techniques for in vitro measurement of antifungal susceptibility that will enable
      prediction of clinical outcome in patients suffering from these infections.
      METHODS. Susceptibility to fluconazole was tested in 156 clinical yeast isolates
      (109, Candida albicans; 19, C. parapsilosis; 12, C. glabrata; 11, C. tropicalis;
      2, C. krusei; 1, C. pelliculosa; 1, C. lambica, and 1, Saccharomyces cerevisiae)
      and two control strains (C. krusei ATCC 6258 and C. parapsilosis ATCC 22019)
      using a simple screening method, CHROMAgar Candida with fluconazole (8 micro
      g/ml). This method was compared with two broth microdilution techniques: the
      reference method (NCCLS, document M27-A) and Sensititre(TM) YeastOne. RESULTS:
      Sensititre(TM) YeastOne showed close agreement with NCCLS M27-A results for all
      species (C. albicans and non albicans). CHROMAgar Candida with fluconazole (8
      micro g/ml) yielded results matching those of the two broth microdilution methods
      for sensitive strains and strains highly resistant to fluconazole (C. krusei and
      C. glabrata), but performed less well with strains displaying dose-dependent
      susceptibility. CONCLUSION: These data suggest that CHROMAgar Candida with
      fluconazole (8 micro g/ml), appears to be a rapid, simple and sensitive screening
      method for detection and identification of fluconazole-susceptible and -highly
      resistant yeasts. However, additional methods should be used to determine whether
      positive growth in this medium is due to resistant strains (MIC > or = 64 micro
      g/ml) or to strains displaying dose-dependent susceptibility (MIC 16-32 micro
      g/ml). The usefulness of CHROMAgar Candida with fluconazole depends on the sample
      source and the species under study.

PMID- 14572383
TI  - [Guidelines for the treatment of invasive fungal infection. Invasive fungal
      infection by Candida spp. Invasive Fungal Infection Study Group (MICOMED) and
      Infection in Transplantation Study Group (GESITRA) of the Spanish Society for
      Infectious Diseases and Clinical Microbiology (SEIMC)].
AB  - These guidelines resume different issues related to the clinical management of
      invasive candidosis in the immunossuppressed patients. They are based on the
      recommendations of the different Drug's Agencies.

PMID- 14572384
TI  - [Furunculoid lesions on the back and leg].

PMID- 14572385
TI  - [Nosocomial fever of unknown origin in a patient with polytrauma].

PMID- 14572386
TI  - [Active immunization against serogroup B Neisseria meningitidis].
AB  - Serogroup B Neisseria meningitidis causes high morbidity and mortality rates over
      the world. This article reviews the current vaccination strategies against this
      microorganism, including vaccines already tested on a large scale, particularly
      those based on class 1 outer membrane proteins, and vaccines in different stages
      of development. The latter involve several approaches, such as modification of
      the polysaccharide capsule composition or conjugation with proteins, and the use
      of recombinant DNA techniques to obtain vaccines that express the prevalent sero
      subtypes in a particular geographical area. The challenges that have emerged with
      the sequencing of the meningococcus B genome are also addressed.

PMID- 14572387
TI  - [Tetracyclines, sulfonamides and metronidazole].
AB  - Tetracyclines form a group of natural and semisynthetic products that acts
      inhibiting the bacterial protein synthesis. They are bacteriostatic agents,
      exhibiting activity against a wide range of organisms, but they are at the
      present of limited use because of their acquired resistance. Doxycycline is
      currently the most frequently used tetracycline in human medicine and it is
      included in the List of Essential Medicines of the World Health Organization.
      Sulfonamides are synthetic, broad-spectrum bacteriostatic antibiotics. They were
      the first effective systemic antimicrobial agents. Their mode of action is based
      on the inhibition of DNA synthesis. Due to their toxicity and high adquired
      resistance their use is currently very low. Metronidazole is the main compound of
      5-nitroimidazole family. It is a very active bactericidal antibiotic against
      anaerobic and some microaerophilic bacteria and it is still very useful in the
      treatment of bacterian and parasitic infections.

PMID- 14572388
TI  - [Mycotic aneurysm of the superior mesenteric artery and intestinal infarction due
      to Aspergillus].

PMID- 14572389
TI  - [Pneumonia associated with bacteremia due to group A streptococcus].

PMID- 14572390
TI  - [Temporal development of pulmonary aspergillosis over a four-year period in a
      teaching hospital].

PMID- 14572391
TI  - [Cerebral infarction due to varicella-zoster virus in a patient with HIV
      infection].

PMID- 14572392
TI  - [Primary care: recommendations of the World Assembly of the WHO, May 2003].

PMID- 14572393
TI  - [Differential health and toxicological features of drug-dependents in treatment
      and in active consumption].
AB  - OBJECTIVES: To describe and compare the demographic and health characteristics
      and drug use patterns in a group of drug dependent individuals who were actively
      using drugs versus those in different types of treatment. To analyze the
      interventions used with the different groups. DESIGN: Descriptive study. SETTING:
      Users at the Association for Aid to Drug Dependent Persons (Asociacion de Ayuda
      al Drogodependiente, ACLAD) in the city of Valladolid in northwestern Spain.
      PATIENTS: 1224 drug dependent persons. MEASURES: We reviewed the medical records
      for a 30-month period for users who were seen at a treatment center and who were
      participating in a damage reduction program. We recorded demographic, drug use
      and clinical variables and compared changes. RESULTS: We studied 1224 patients in
      all. One-third had human immunodeficiency virus infection, 63% had markers for
      previous hepatitis A infection, 48% had markers for hepatitis B, and 68.5% for
      hepatitis C. The Mantoux test was positive in 39.1%. We found differences in the
      prevalence of infections between active drug users and users in treatment,
      between drug dependent persons receiving different types of treatment, and
      between different periods of study. CONCLUSIONS: There were clear differences in
      demographic and health characteristics and drug use patterns between users. Those
      who were not in rehabilitation were in worse health, and were studied in less
      detail that other groups of drug users. During follow-up we noted a slight
      improvement in their health conditions, along with a tendency toward improved
      primary care interventions.

PMID- 14572394
TI  - [Commentary: adapting resources to the needs of drug dependent persons: how much
      longer will standardization take?].

PMID- 14572395
TI  - [Travelling immigrants].
AB  - OBJECTIVES: To characterise travelling immigrants and the international movements
      they undertake. To identify the risk journeys that this population makes and to
      assess the international preventive activities for them compared with those for
      autochthonous travellers. DESIGN: Retrospective, observational study. SETTING:
      Unit of International Health (UIH) Santa Coloma de Gramenet (Barcelona), in the
      Barcelones Nord i Maresme Health Area, Primary Care Division of the Catalan
      Institute of Health. PARTICIPANTS: Patients seen between June 1999 and June 2002
      (n=1163) at the UIH. They were divided into two groups, depending on their
      origins: those born inside (autochthonous group; no=1019) or outside (immigrant
      group; n1=144) the European Union. MAIN MEASUREMENTS: Age, country of origin,
      length of residence in Spain, interval between consultation and journey, reason
      for journey, destination, duration of the journey, kind of journey, stay in rural
      or isolated area, exposure to malaria, vaccinations and anti-malaria
      chemoprophylaxis prescribed, and overall risk of journey. RESULTS: Immigrants
      spent more time abroad than autochthonous people (mean 43.5 days; 95% CI, 37.9
      49.1; and 15.8 days, 95% CI, 14.9-16.7, respectively; P<.0001). Periods between
      the journey and the consultation at the UIH were generally similar in the two
      groups (mean of 26.8 days for immigrants and 30.41 days for autochthonous people;
      ns), although the immigrants consulted more often in periods of less than 15 and
      7 days (P<.005). 31.9% of immigrants stayed in areas of high malaria transmission
      (95% CI, 24.4%-39.6%) vs 21.3% (95% CI, 18.8%-23.8%) of autochthonous people
      (P=.04). Overall, immigrants made more risk journeys than autochthonous people
      (54.8% vs 43.1%; P<.01). No significant differences between the two groups were
      found in terms of quality in the administration of the international vaccinations
      prescribed. Compliance with the guidelines for anti-malaria chemoprophylaxis was
      less in the immigrant group than in the autochthonous one (36% vs 84%; P<.005).
      CONCLUSIONS: The immigrant group in our environment needs to be thought of as a
      risk group for catching and importing tropical diseases during their
      international movements. They form a population for whom international preventive
      measures should be prioritized.

PMID- 14572396
TI  - [Prevalence of urinary incontinence and linked factors in men and women over 65].
AB  - OBJECTIVES: To calculate the prevalence of urinary incontinence and to identify
      linked factors in a population of elderly people living in their homes. DESIGN:
      Population survey. SETTING: Leganes (Madrid). PARTICIPANTS: Representative sample
      of people over 65 registered in Leganes (n=1560). Two interviews at home were
      conducted. The second interview included a medical examination. The reply rate
      was 75% (n=1150). MAIN MEASUREMENTS: Frequency of involuntary losses of urine and
      use of medication and absorbents, health status, use of diuretics and oxybutinin,
      and demographic and social variables. RESULTS: The prevalence of urinary
      incontinence was 14% (95% CI, 11%-17%) in men and 30% (95% CI, 26%-34%) in women.
      Advanced age was associated with greater prevalence in men but not in women. In
      the multivariate analysis, factors associated with urinary incontinence were
      comorbidity and cognitive deficit. In addition, in women, high Body Mass Index
      and seriously limited movement were added factors. 20% of women and 5% of men
      over 65 used absorbents. The use of diuretics and the low number of patients
      receiving specific treatment for urinary incontinence suggested that there was
      low detection of this problem. CONCLUSIONS: Urinary incontinence is common and
      could be better detected and treated in primary care. Prevention of urinary
      incontinence in women should begin before old age.

PMID- 14572397
TI  - [Study of the prevalence of burnout in doctors in the Health Area of Talavera de
      la Reina].
AB  - OBJECTIVE: To determine the degree of burnout or professional wear-and-tear in
      doctors from the Talavera de la Reina Health Area and linked factors. DESIGN:
      Transversal, descriptive study. PARTICIPANTS: Doctors in primary care (PC)
      (n=106) and specialist care (SC) (n=129). MEASUREMENTS AND RESULTS: Maslach
      Burnout Inventory (MBI) questionnaire and a survey with social and demographic
      variables and suggestions. Both were anonymous and self-administered. RESULTS:
      144 (61.27%) answered, 63 from PC and 81 SC. 72.2% were male, with a mean age of
      45 (with little variability between PC and SC). Average years worked were 18.65.
      102 (70.83%) worked cover. 85 (59.02%) had an indefinite contract, 49 (34.02%) a
      temporary one, and 10 (6.94%) other kinds. 76.4% of the professionals suffered
      burnout (moderate in 38.9% and high in 37.5%). The difference between PC and SC
      burnout (85.7% vs 69.1%) was statistically significant. In the remaining
      variables studied (age, sex, marital status, working of cover shifts.) we found
      no significant differences. Among suggestions to mitigate burnout were demands to
      support improvements in working conditions, greater personal and professional
      recognition, involvement of the government and management, economic remuneration,
      providing more training and research, etc. CONCLUSIONS: Professional wear-and
      tear or burnout is very high in our area, and is higher in PC than in SC.

PMID- 14572398
TI  - [Usefulness of physical examination at a primary health centre to diagnose infant
      pneumonia caught in the community].
AB  - OBJECTIVE: To determine the diagnostic usefulness of three clinical signs
      (temperature, cough, crepitant stertor) for diagnosing pneumonia in children. To
      evaluate the agreement of two radiologists in evaluating thoracic x-rays (TXR).
      DESIGN: Study of diagnostic tests. SETTING: Primary care. PARTICIPANTS: 350
      clinical histories of children who had an urgent TXR to diagnosis pneumonia
      between 1st January 1996 and 30th June 1999. MAIN MEASUREMENTS: a) Prevalence of
      pneumonia in the entire sample and two age-based sub-groups: aged 5 years and
      under, and over 5; b) positive probability quotients (PQ+) and negative ones (PQ
      ) and 95% confidence intervals (95% CI). The TXR was seen as the reference
      standard, and c) kappa index (kappa) for inter-radiologist concordance. RESULTS:
      Prevalence: the entire sample, 22.9% (95% CI, 18.5-27.3); children aged 5 or
      less, 20.4% (95% CI, 15.6-25.2); aged over 5, 31.3% (95% CI, 21.1-41.4). The
      signs studied were only of any use in confirming the diagnosis in children over
      5: PQ+ was 3.52 (1.28-9.69). Radiologists coincided in their diagnosis in 93.1%
      of the TXR (kappa=0.8; 95% CI, 0.77-0.83). CONCLUSIONS: This study did not prove
      that there was a sub-grouping of clinical signs which confirmed unmistakably the
      diagnosis of pneumonia in children.

PMID- 14572400
TI  - [Research and teaching units supporting primary care management].

PMID- 14572399
TI  - [Sexual behaviour among school adolescents in Cordoba].
AB  - OBJECTIVE: To know sexual behaviour among school teenagers and to determine
      different risk behaviors and groups with specific needs of health education.
      DESIGN: Cross-sectional study. SETTING: High-schools from Cordoba. PARTICIPANTS:
      893 teenagers students selected by random sample. MAIN MEASUREMENTS: Anonymous
      self-rated survey about sexual behaviour and uses of contraceptives methods. MAIN
      RESULTS: The average age was 17.16 years (95% CI, 17.05-17.26), 48% males. 22.9%
      have had completed sexual relations; there were mainly girls (P=.001). The
      average age for the first relation was 16.64 years (95% CI, 16.45-16.82), with no
      difference between gender. Among girls, first sexual intercourse use to be with
      their regular partners (P<.001). 48% of the girls have had one or more sexual
      intercourse per week, that was only a 19.5% among boys (P<.001). 82% had used a
      contraceptive method at the first time, and the condom was the method more
      frequently used. CONCLUSIONS: 20% of school teenagers have had complete sexual
      intercourse, most of them before 18 years. Girls have more frequently sexual
      relations, usually with their regular partners. Condom is the contraceptive
      method more frequently used.

PMID- 14572401
TI  - [Effectiveness of non-pharmacological primary care methods for giving up tobacco
      dependency].
AB  - OBJECTIVE: To determine the effectiveness of a systematic and intensive programme
      of tobacco counselling, as against brief anti-tobacco counselling. DESIGN:
      Controlled and randomised clinical trial. SETTING: Primary care medical and
      nursing clinics at an urban Health Centre in Getafe. PARTICIPANTS: Smokers who
      request health care at the medical clinics for any reason during the recruitment
      period, who satisfy the inclusion criteria and who want to take part in the
      study. The inclusion criteria are: 18 years old or more, people who have smoked
      daily during the previous month any amount of cigarettes, and high motivation
      (score over 7 on the Richmond test). INTERVENTION: The 110 patients recruited by
      each doctor will be included, depending on the clinic they come from, in the
      control group (brief counselling) or the intervention group (intensive
      counselling). For the patients in the intervention group, monitoring visits will
      be programmed for 6 months after giving up. Both groups will be called by phone
      after a year to see if they are still smoking. MAIN MEASUREMENTS: Abstinence at
      12 months. SECONDARY MEASUREMENTS: a) Recorded at the start: personal details,
      medical history and smoking history; b) recorded at the consultations:
      abstinence, date of first giving up and symptoms of withdrawal syndrome.
      DISCUSSION: The study will define the role of nursing professionals in taking
      patients off tobacco and will help define the effectiveness of non-medical
      methods to achieve this.

PMID- 14572402
TI  - [Programme to introduce and develop minor out-patient surgery in primary care].
AB  - INTRODUCTION: Despite the priority placed on it, minor surgery is not performed
      enough in primary care (PC). OBJECTIVE: To create and evaluate a programme to
      introduce and develop minor out-patient surgery in primary care in a way that
      matches our health areas needs. DESIGN: Prospective, longitudinal and descriptive
      study. SETTING: Health Area 19 (Valencian Health Service): Surgery Department of
      Elche Hospital and 3 health centres (HC) (Altabix, Crevillente and Santa Pola).
      PARTICIPANTS: PC doctors and specialist surgeons. STAGES: a) Selection of HC.
      Working out protocol of kind of patient, pathology, paper-work and establishment
      of work circuits; b) surgical sessions at the HC, performed by two surgeons
      assisted by PC doctors (surgical leaders) and with surgical instruments from the
      hospital; c) surgery performed by PC doctors supervised by a surgeon, with
      instruments and the sterilisation circuit in the HC. The programme ends up with
      the PC doctors surgical autonomy and with use of the HCs own resources. RESULTS:
      41 surgical sessions took place (14 in Altabix, 14 in Crevillente and 13 in Santa
      Pola). 335 patients were operated on in 398 surgical procedures (55.5% excisions,
      34.9% electrocoagulation, 9.6% others). There were no immediate complications.
      The monthly evolution in the number of patients was constant, with a mean of
      10.22 interventions per session. 36 doctors referred patients and 24 of them
      performed a surgical procedure. CONCLUSIONS: A practical and safe programme to
      introduce and develop minor surgery in PC, to the satisfaction of doctors and
      patients.

PMID- 14572403
TI  - [Dilemmas and alternatives in the evaluation of family doctor training].

PMID- 14572404
TI  - [B12 vitamin deficiency and oral treatment. An option as efficient as (still)
      infrequently used].

PMID- 14572405
TI  - [Local infiltration in joint and soft-part pathology at a health centre].

PMID- 14572406
TI  - [Differences in the likelihood of caesareans, associated with dependency on
      hospitals, the volume of cases and the obstetric risk].

PMID- 14572407
TI  - [Evolution of opiate consumption in a Madrid area between 1997 and 2001].

PMID- 14572408
TI  - [Monitoring of hypertransaminasaemia in primary care clinics].

PMID- 14572411
TI  - [Medical research in small populations].

PMID- 14572409
TI  - [Interactions or potentially dangerous associations?].

PMID- 14572412
TI  - [Anti-flu vaccination in health staff: problem of consciousness-raising or of
      conscience?].

PMID- 14572413
TI  - Helicobacter pylori and allergic disease.

PMID- 14572414
TI  - Mite antigens enhance ICAM-1 and induce VCAM-1 expression on human umbilical vein
      endothelium.
AB  - Although sublingual allergen-specific immunotherapy has been proved to be
      effective in the treatment of allergic diseases, controversy surrounds the means
      by which such a local therapy can induce systemic immunological changes. Adhesion
      molecules are critical in the regulation of leukocyte traffic. It has been
      hypothesized that allergenic extract, administered locally, may induce an up
      regulation of the mucosal vessel vascular adhesion molecules (CAMs) resulting in
      local recruitment of circulating inflammatory cells. In the present study we
      investigated whether the mite antigens, Der p1 and Der p2, can modulate CAM
      expression of human endothelial cells (HEC). To do this, slices of whole human
      umbilical cord vein underwent short-term (8 hours) cultures in the presence or
      absence of mite antigen (baseline, unstimulated controls). Cryostatic sections of
      the specimens were then evaluated immunohistochemically for expression of
      intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule
      (VCAM-1) molecules. The results revealed that while Der p1 is capable of
      significantly up-regulating ICAM-1 and VCAM-1 on HEC, Der p2 antigen moderately
      up-regulates ICAM-1 expression but is ineffective in modulating VCAM-1. Although
      preliminary, these results clearly support the hypothesis that at least some of
      the effects of sublingual immunotherapy may derive from inflammatory cell
      recruitment at the site of allergen release.

PMID- 14572415
TI  - Allergy to asticot maggots. Identification of allergens.
AB  - There are some written reports of allergic reactions after contact with Asticot
      larvae in anglers and occupationally exposed workers. Clinical and immunological
      studies were performed to confirm the allergens involved in the case of a 12-year
      old male who developed respiratory symptoms shortly after contact with Asticot
      maggots used as fish bait. METHODS AND RESULTS: Aqueous extracts of Asticot
      maggots were taken for in vivo and in vitro tests. The protein concentration as
      determined by turbidimetric assay was 1.4 mg/ml. Skin prick test with Asticot
      extract was positive with an immediate response. Ten atopic and ten nonatopic
      control subjects did not react to the extract. Specific serum IgE antibodies
      against Asticot were found in the patient's serum (ELISA). Coomasie staining
      after SDS-PAGE separation of Asticot extract showed three protein bands of 30, 40
      and 60 kDa. IgE immunoblot showed one antigenic band of 60 kDa specifically
      recognized by the patient's IgE. Specific nasal challenge test with Asticot
      extract using a Rhinospir 164 rhinomanometer showed immediate response (1/10
      w/v), with a 200% increase in nasal resistances from baseline. CONCLUSIONS: One
      main allergen of MW 60 kDa was specifically recognized by our patient's IgE.
      There are no previous reports in the literature that characterize the allergens
      involved in Asticot hypersensitivity. Asticot maggots should be taken into
      account as a possible causative agent of respiratory symptoms due to a type I
      hypersensitivity mechanism in anglers who are exposed to emanations of these live
      fish baits.

PMID- 14572416
TI  - Efficacy and tolerability of short-term specific immunotherapy with pollen
      allergoids adjuvanted by monophosphoryl lipid A (MPL) for children and
      adolescents.
AB  - BACKGROUND: Specific immunotherapy (SIT) with pollen allergoids formulated with
      the Th1-inducing adjuvant 3-deacylated monophosphoryl lipid A (MPL adjuvant,
      Corixa) has shown good efficacy and tolerability in the treatment of pollen
      allergies in adults. The aim of this study was to evaluate this treatment in
      children and adolescents aged 6-17 years old who were sensitive to grass/rye or
      tree pollens. METHODS: An open, multicenter study was performed using 90 children
      and adolescents. The patients received four subcutaneous injections of grass/rye
      (n = 64) or tree pollen allergoids (n = 26) adsorbed to L-tyrosine and containing
      MPL adjuvant. Efficacy was measured by symptom and medication scoring, skin prick
      test reactivity and IgG/IgE antibody responses. Tolerability was monitored by
      recording adverse events. RESULTS: Both grass/rye and tree pollen treatment
      groups showed significant reductions in symptom scores and anti-allergic
      medication use compared with the previous pollen seasons (p < 0.01 in all cases).
      After therapy, skin prick test reactivity was significantly reduced in both
      groups and pollen-specific IgG was significantly increased in both groups whereas
      little change was apparent in pollen-specific IgE. Overall tolerability was
      similar to results obtained in previous studies in adults. CONCLUSION: Short-term
      SIT using four injections of grass/rye or tree pollen allergoids adsorbed to L
      tyrosine and with MPL adjuvant was shown to be effective with good tolerability.
      The treatment compared favorably with previous studies in adults.

PMID- 14572417
TI  - Proteinase and gelatinolytic properties of a bat feces extract.
AB  - It was previously demonstrated that a bat feces extract (BAT) was able to produce
      a specific IgG in animals, a specific IgE in respiratory atopic humans and a
      hypersensitivity pneumonitis in guinea pigs. As numerous allergens (such as house
      dust mite, cockroaches and pollens) revealed a enzymatic activity measured by
      different assays we decided to study the proteinase and the gelatinolytic
      activities of the BAT. Several protease inhibitors such as E-64, TLCK, TPCK,
      PMSF, leupeptin, o-phenantroline and pepstatin-A were applied to establish the
      chemical properties of the enzymatic activity. These assays revealed a serine
      trypsin-like proteolytic and gelatinolytic activities specially at pH 8,5. On the
      other hand, two bands of 21 and 40 kDa reacted with the human atopic sera
      suggesting a possible correlation between allergenicity and proteinase activity.
      Their role in the etiology of perennial rhinitis and asthma requires further
      investigations.

PMID- 14572418
TI  - Psychological problems in Turkish asthmatic children and their families.
AB  - BACKGROUND: Asthma is a chronic respiratory disorder characterized by recurrent
      episodes of impaired breathing. The disease causes psychological problems due to
      hospitalization, long-term medication use, and restricted social life. OBJECTIVE:
      The aim of this study was to investigate the relationship between the severity
      and duration of asthma and psychological problems in asthmatic children, as well
      as the probability of maternal anxiety. METHODS: Thirty-seven children with mild
      asthma, 55 with moderate asthma and eight with severe asthma were compared with
      50 healthy children. The severity of asthma was evaluated using the Pearlman
      Bierman classification. Psychological adjustment was measured using the Achenback
      child Behavior checklist and Spielberger's scale. RESULTS: Emotional factors and
      family dynamics were found to be triggering factors for disease attacks in 16% of
      children with mild asthma, 38% of those with moderate asthma and 63% of those
      with severe asthma (p < 0.05). There was no significant difference in the mean
      maternal anxiety score between the disease severity groups (p > 0.05). The mean
      depression score was significantly higher in children with moderate and severe
      asthma than in those with mild asthma (p < 0.05). Disease duration showed no
      effect on depression and anxiety. CONCLUSION: Both asthmatic children and their
      mothers are negatively affected by the disease.

PMID- 14572419
TI  - Auriculotemporal nerve syndrome.
AB  - INTRODUCTION: Auriculotemporal nerve syndrome is characterized by erythema,
      perspiration, heat and pain localized in the area supplied by the
      auriculotemporal nerve in response to gustatory stimuli after the ingestion of
      different types of food. This syndrome may be confused with food allergy. CASE
      REPORT: A 21-year-old woman complained of erythema, sweat and heat in the right
      cheek after intake of several foods such as chocolate, fruits, and nuts for the
      previous 8 months. She had fractured her jaw two years previously. METHODS: Skin
      prick tests were performed with a standard battery of common inhalant allergens
      and with an extensive panel of food allergens. Prick-by-prick tests were also
      performed with fruits, nuts, and cacao. Total and specific IgE were measured.
      Open oral food challenge test was performed. RESULTS: Skin prick tests were
      positive for grass and olive pollen. Prick-by-prick tests and specific IgE
      antibodies to the different foods were all negative. Open oral challenge test
      with apple reproduced the symptoms. CONCLUSIONS: This benign syndrome is often
      misdiagnosed as a food allergy.

PMID- 14572420
TI  - Fixed drug eruption due to loratadine.
AB  - We present the clinical case of a 8-years-old boy suffering a fixed drug reaction
      attributed to the oral intake of loratadine. He is an atopic child with perennial
      rhinitis and asthma and marked hypersensitivity to the house-dust mite
      Dermatophagoides pteronyssinus who is receiving inhaled corticosteroids and b2
      agonists ad libitum plus specific immunotherapy with the mite. When the boy
      received loratadine to alleviate his nasal symptoms he suffered a well-defined
      erythematous and oedematous plaque in his right elbow that disappeared without
      treatment in one week. Several methods such as the patch-tests, the UBCT or ultra
      brief-challenge test (our version of the peroral provocation one) and the skin
      biopsy were applied. The UBCT and the skin histopathology were the most important
      techniques to assure the suspected diagnosis. Other antihistamines such as
      ebastine and cetirizine as well as some excipients used as controls were all
      negative. Conventional prick or intradermal skin tests with the drug were not
      performed because we considered that they were useless in this case.

PMID- 14572421
TI  - Familial presentation of occupational hypersensitivity pneumonitis caused by
      aspergillus-contaminated esparto dust.
AB  - Esparto grass (Stipa tenacissima), which is commonly found in the Mediterranean
      area, has a wide variety of uses. Five plaster workers from the same family
      developed cough, dyspnea, malaise, and fever after exposure to the esparto fiber
      used in their work for the previous few years. They showed a significant decrease
      in symptoms when away from work. Precipitating antibodies against an esparto
      extract were found in the sera of all patients. Specific IgG antibodies against
      Aspergillus fumigatus were detected. A. fumigatus was identified after
      microbiologic evaluation of esparto fiber samples. The dust derived from fungi
      contaminated esparto fibers can cause hypersensitivity pneumonitis in exposed
      subjects. The causative antigen is A. fumigatus. When esparto fibers were
      strongly contaminated by fungi, all the workers developed a clinical picture
      compatible with hypersensitivity pneumonitis. The coincidental finding of an
      occupational and a familiar condition is unusual.

PMID- 14572422
TI  - The epidemiology of cigarette smoking in Hong Kong Chinese women.
AB  - BACKGROUND: Smoking in women is a well-recognized public health problem. In many
      developed countries, cigarette smoking is now the single most important
      preventable cause of premature death in women. There are relatively few data on
      the epidemiology of cigarette smoking in Asian women, and this study examined the
      prevalence of and factors predisposing Chinese women to smoke cigarettes in Hong
      Kong. METHOD: A territory-wide random telephone survey of 26,716 households in
      Hong Kong was conducted. A total of 1064 current smokers and 291 ex-smokers were
      identified in these household, and in-depth interviews of 791 current smokers,
      221 ex-smokers, and 1012 controls were conducted. RESULTS: The prevalence of
      cigarette smoking was 4.5% in women who were 25 years or younger, 2.6% in women
      aged 46-65 years, and 2.2% in women aged 65 years or older. Sixty-four percent of
      current smokers started when they were 19 years or younger. The main reasons for
      the initiation of cigarette smoking were the influence of friends, curiosity,
      feeling bored, or being idle. Current smokers and ex-smokers tended to have
      positive images of women who smoked. The following risk factors were found to be
      significant for cigarette smoking: less than university education, unemployment,
      being divorced, having a husband who smoked, and a low score on the perceived
      harms of cigarette smoking. CONCLUSION: Cigarette smoking is more prevalent in
      younger women in Hong Kong; and psychosocial issues should be addressed to
      prevent future epidemics.

PMID- 14572423
TI  - Is absolute amount or change in exercise more associated with quality of life in
      adult cancer survivors?
AB  - BACKGROUND: The present study examined the association between quality of life
      (QOL) in adult cancer survivors and the (a) absolute current amount of exercise
      and (b) change in exercise since cancer diagnosis. METHODS: Three hundred fifty
      two (mean age = 59.6) adult cancer survivors recruited from outpatient clinics in
      four states (Iowa, Wisconsin, Minnesota, and Georgia) and a minority support
      groups completed a survey including demographic, medical, exercise behavior, and
      QOL questions. RESULTS: Hierarchical multiple regression analyses controlling for
      important demographic and medical variables showed that adult cancer survivors
      who currently exercised three times per week had significantly higher QOL than
      those who did not (beta = 0.13, P < 0.05). Furthermore, compared to adult cancer
      survivors who exercised less since their cancer diagnosis, those who maintained
      (beta = 0.28, P < 0.08) or increased (beta = 0.24, P < 0.01) the amount of
      exercise they performed since their cancer diagnosis had significantly higher
      QOL. Finally, examination of the DeltaR(2)(adjusted) between the two exercise
      models showed that the absolute current amount of exercise explained an
      additional 1% (DeltaR(2)(adjusted) = 0.01 P < 0.05) of the variance in QOL
      whereas the change in exercise explained an additional 7% (DeltaR(2)(adjusted) =
      0.07, P < 0.01). CONCLUSION: Change in exercise since cancer diagnosis may be a
      more important correlate of QOL in adult cancer survivors than the absolute
      current amount of exercise.

PMID- 14572424
TI  - Social class, family, and life-style factors associated with overweight and
      obesity among adults in Peruvian cities.
AB  - BACKGROUND: Overweight and obesity have reached epidemic proportions in Latin
      America. OBJECTIVE: The purpose of this study was to explore social and
      behavioral factors associated with obesity in Peruvian cities. DESIGN: Between
      1998 and 2000 health examination surveys were conducted among adults in 1176
      families identified in six cities. Stratified by social class, multistaged random
      sampling was used. Using body mass index (weight (kg)/height (m)(2)), men and
      women were classified into normal weight (BMI <25), overweight (BMI 25-29), or
      obese (BMI > or =30); abdominal circumference (> or =94 cm in men and > or =84 cm
      in women) further identified morbidity risk. Several demographic, social, and
      behavioral variables were collected following standardized procedures. RESULTS:
      Adjusting for age, 37% of women were categorized as normal weight, 40%
      overweight, and 23% obese; corresponding figures for men were 40, 44, and 16%.
      More developed cities, e.g., Lima, Arequipa, and Ica, had the largest prevalence
      of overweight and obesity for both men and women. Adjusted logistic models showed
      that BMI > or =25 was positively correlated with age; whereas, education was
      negatively associated, only among women. Other significant associated factors of
      overweight included city of residence, television viewing > or =4 h daily in
      women, and underestimation of body weight status. CONCLUSIONS: The study showed
      elevated rates of overweight across the income level spectrum. Factors such as
      urban development stage, income, education, and gender posed differential
      relationships with the risk of overweight and must be considered in designing
      future public health interventions. Underestimation of body weight status and
      sedentary behavior may also constitute specific areas of intervention.

PMID- 14572425
TI  - Final results of the Maryland WIC Food for Life Program.
AB  - BACKGROUND: The few randomized community trials in middle-income populations that
      tried to modify multiple dietary risk factors for cancer only demonstrated small
      changes. This trial sought to decrease the percent of calories derived from fat
      and to increase fruit, vegetable, and fiber intake among low-income women served
      by the Special Supplemental Nutrition Program for Women, Infants, and Children
      (WIC) in Maryland. METHODS: We conducted six-month intervention programs for 1055
      women at ten WIC sites; 1011 women served as controls. Intervention participants
      were invited to five interactive nutrition sessions and were sent written
      materials. Controls received usual care. Women were surveyed at baseline, two
      months post intervention, and one year later. All analyses conducted used an
      intention-to-treat paradigm. RESULTS: Mean differences (intervention-control) in
      change from baseline were for percent calories from fat -1.62 +/- 0.33% (P <
      0.0001), for consumption of fruits and vegetables 0.40 +/- 0.11 servings (P =
      0.0003), and for fiber intake 1.01 +/- 0.31 grams (P = 0.001). These differences
      in change were related in a dose-response relationship to the number of sessions
      women attended and remained significant one year post-intervention for the first
      two outcomes. CONCLUSIONS: Multiple dietary improvements can be achieved in a low
      income population with an effective, multi-faceted intervention program. The
      changes in this trial exceeded those in previous community trials conducted in
      higher SES populations.

PMID- 14572426
TI  - Effects of the year 2000 influenza vaccine delay on elderly patients' attitudes
      and behaviors.
AB  - BACKGROUND: A substantial delay in distribution of influenza vaccine occurred in
      the 2000-2001 influenza season. Our objective was to quantify the impact of this
      delay on immunization rates, location of receipt of immunization, and patient
      attitudes and beliefs about the influenza vaccine. METHODS: Inner-city and
      suburban medical practices that received influenza vaccine supply on-time or late
      in the season (late-receipt) were selected. A random sample of elderly patients
      from each practice completed telephone interviews. RESULTS: Of 775 eligible
      patients, we interviewed 72%. The odds of receiving influenza vaccine in late
      receipt practices compared to on-time practices did not significantly differ in
      either the suburban stratum (adjusted OR = 0.9, 95% CI 0.5-1.6) or the inner-city
      stratum (adjusted OR = 1.5, 95% CI 0.8-2.8). Very few respondents (4%-11%)
      reported changes in their beliefs about the vaccine, its safety or efficacy, from
      previous years. More patients in late-receipt practices reported receiving
      influenza vaccine at locations other than their regular doctor's offices in the
      shortage year compared with the previous year. CONCLUSIONS: The 2000-2001
      influenza vaccine delay changed vaccination location, but did not change
      influenza vaccination rates.

PMID- 14572427
TI  - Psychosocial correlates of intention to undergo prophylactic oophorectomy among
      women with a family history of ovarian cancer.
AB  - BACKGROUND: The purpose of this study was to examine sociodemographic and
      psychosocial correlates of intention to undergo prophylactic oophorectomy among
      women with a family history of ovarian cancer. METHODS: Participants were 76
      women enrolled in a familial cancer risk assessment program. Psychosocial
      assessments were collected upon entry into the program and included measures of
      perceived risk of developing ovarian cancer, perceived benefits and limitations
      of prophylactic oophorectomy, and psychological distress. In addition,
      respondents were asked whether they intended to undergo prophylactic oophorectomy
      in the following 12 months. RESULTS: Thirty-four percent reported intention to
      have surgery within 12 months. Logistic regression analyses indicated that
      intention to undergo surgery was associated with several psychosocial factors
      including greater perceived risk of developing ovarian cancer and greater
      perceived benefits of surgery. CONCLUSIONS: Women who have heightened risk
      perceptions and who perceive there to be many benefits of surgery may be more
      inclined to undergo the procedure, possibly without fully considering the
      potential limitations and consequences of surgery. These findings suggest the
      need for education and risk counseling designed to facilitate informed decision
      making among not only high-risk women, but also women who perceive themselves to
      be at increased risk.

PMID- 14572428
TI  - A population-based dietary intervention trial in a high-risk area for stomach
      cancer and stroke: changes in intakes and related biomarkers.
AB  - BACKGROUND: Dietary intervention is one of the important fields in cancer and
      cardiovascular disease prevention. The Hiraka Dietary Intervention Study is a
      community-based randomized cross-over trial designed to develop an effective
      dietary modification tool and system in an area with high mortality of stomach
      cancer and stroke. METHODS: The subjects were 550 healthy volunteers and were
      randomized into two groups with tailored dietary education to decrease sodium
      intake and to increase vitamin C and carotene intakes either in the first year
      (intervention group) or in the second year (control group). Dietary changes were
      assessed using a validated self-administered diet history questionnaire, fasting
      blood samples, and 48-hour urine samples, which were obtained before and after
      the one year period. RESULTS: During the first year, changes differed
      significantly between the intervention and control group for both dietary sodium
      intake (-384 and +255 mg/day, intervention and control respectively, p < 0.001)
      and urinary sodium excretion (-1003 and -84 mg/day, p < 0.001). Although
      favorable net changes were also observed in dietary carotene (+418 and +220
      mug/day, p < 0.05) and vitamin C (+13 and +2 mg/day, p < 0.05), the serum level
      differences were modest (+13 and -25 mg/L, p = 0.09 for carotene, +0.1 and -0.5
      mg/L, p = 0.07 for ascorbic acid). CONCLUSION: The present dietary intervention
      strategy effectively decreased sodium and increased carotene and vitamin C
      intakes, although the former was more distinct.

PMID- 14572429
TI  - Screening rarely screened women: time-to-service and 24-month outcomes of
      tailored interventions.
AB  - BACKGROUND: Managed care organizations and others reaching out to underscreened
      women seek strategies to encourage mammogram and Pap screening. METHODS: Female
      HMO members aged 50-69 years and overdue for a mammogram and a Pap test (n = 501)
      were followed for 24 months after interventions began. An Outreach intervention
      (tailored letters and motivational telephone interviews), an Inreach intervention
      (motivational interview delivered in clinics), and a Combined Inreach/Outreach
      intervention were compared to Usual Care at 24 months. Logistic regression and
      Cox hazard models examined predictors of obtaining screening services and time-to
      service, respectively. RESULTS: Compared with Usual Care, the odds of Outreach
      women aged 50-64 obtaining a mammogram (OR = 2.06; 95% CI = 1.59-5.29), a Pap
      test (OR = 1.97; 95% CI = 1.12-3.53), or both (OR = 2.53; 95% CI = 1.40-4.63)
      remained significantly increased at 24 months. The average time-to-service for
      Outreach women was reduced by 4 months. Outreach effects persisted despite
      intensive, ongoing health plan efforts to improve screening of all women.
      CONCLUSIONS: This brief, tailored outreach intervention was an effective strategy
      for encouraging cervical and breast cancer screening among women overdue for both
      screening services. It also shortened time-to-service, an important benefit for
      early detection and treatment. Alternative strategies are needed for women who
      remain unscreened.

PMID- 14572431
TI  - Racial, ethnic, socioeconomic, and access disparities in the use of preventive
      services among women.
AB  - BACKGROUND: In this article we estimate the variations in receipt of age
      appropriate preventive services among adult women between 21 and 64 years of age,
      by race and ethnic group, socioeconomic status, and access to health care. We
      also assess whether differences in access to care and socioeconomic status may
      explain racial and ethnic differences in the use of preventive services. METHOD:
      Nationally representative data on adult women from the Medical Expenditure Panel
      Survey were used to estimate the effect of socioeconomic characteristics on the
      receipt of each preventive service. Receipt of each of four preventive services
      cholesterol test, blood pressure reading, and two cancer screening tests
      (Papanicolaou smear, mammogram)-according to the 1996 recommendations of the U.S.
      Preventive Services Task Force were examined. RESULTS: An overwhelming majority
      of adult women (93%) had had a blood pressure reading within the last 2 years.
      Eighty-four percent of women had had their cholesterol checked within the last 5
      years. Seventy-five percent of women had received a mammogram and 80% received
      Pap tests. College education, high income, usual source of care, and health
      insurance consistently predicted use of preventive services. These factors also
      explained ethnic disparities in the receipt of preventive services between
      Latinas and white women. CONCLUSIONS: The results from our study are encouraging
      because only a minority of women do not receive age-appropriate preventive
      services. However, low socioeconomic status, lack of insurance, and lack of a
      usual source of care represent significant barriers to preventive care for adult
      women.

PMID- 14572430
TI  - A review of 25 long-term adolescent tobacco and other drug use prevention program
      evaluations.
AB  - BACKGROUND: Although the initial effectiveness of psychosocial strategies
      programming in preventing smoking and other drug abuse among adolescents has been
      well established through literature reviews and meta-analyses, much less evidence
      exists for the long-term follow-up success of these interventions. The primary
      goal of this paper, therefore, is to summarize the effectiveness of published
      program evaluation studies that have followed adolescents across the transitional
      period between junior high and high school for a period of at least 2 years.
      METHODS: Studies for inclusion in this review were accessed primarily through a
      computerized search of Medline, Healthstar, and PsychINFO databases. Intervention
      studies that met five core criteria were retained for review. Two authors
      independently abstracted data on study characteristics, methodology, and program
      outcomes. RESULTS: Search results yielded 25 studies suitable for examination.
      The majority of these studies reported significant program effects for long-term
      smoking, alcohol, and marijuana outcomes, while indicating a fairly consistent
      magnitude of program effects. CONCLUSIONS: This review provides long-term
      empirical evidence of the effectiveness of social influences programs in
      preventing or reducing substance use for up to 15 years after completion of
      programming. However, this conclusion is still somewhat tenuous given the lack of
      significant program effects reported in several studies and the great variability
      that existed in the level of internal and external validity across all studies.

PMID- 14572432
TI  - Anger types and the use of cigarettes and smokeless tobacco among Native American
      adolescents.
AB  - BACKGROUND: Although tobacco use appears common among Native Americans, the study
      of dual use of cigarettes and smokeless tobacco has been neglected. The current
      study examines tobacco use among a sample of Native American adolescents. Also,
      it considers how the psychological factor of anger may relate to tobacco use.
      METHODS: The participants were 513 Native American students from a national
      sample in grades 6, 8, and 10 in the United States. Cluster analysis was used to
      identify anger types, and these types were compared on their tobacco use.
      RESULTS: Cluster analysis identified four anger types. One type was the
      Externalizing Type, characterized by the tendency to show externalizing behaviors
      such as fighting and yelling. This type had an elevated rate of tobacco use. In
      terms of an odds ratio, the Externalizing Type was about 10 times more likely to
      smoke, about 6 times more likely to use smokeless tobacco, and about 8 times more
      likely to show dual use. The majority of dual users were the Externalizing Type.
      CONCLUSIONS: The results suggest that externalizing anger types are more likely
      to use tobacco, and that smoking cessation programs for teens could be more
      effective when they address anger issues.

PMID- 14572433
TI  - Arab-American adolescent tobacco use: four pilot studies.
AB  - OBJECTIVES: Four pilot studies were conducted to determine the (1) current
      tobacco use patterns and predictors among 14- to 18-year-old Arab-American
      youths; (2) psychometric properties of study measures (English and Arabic); (3)
      cultural appropriateness of Project Toward No Tobacco (TNT) for intervention; (4)
      accessible population for a longitudinal study. METHODS: Three studies were
      descriptive and one used a pretest-posttest design. From four Pilot Focus groups
      (N = 28 smokers) key tobacco use themes emerged along with information on study
      measures and the Project TNT intervention; Pilot Intervention tested the tailored
      Project TNT intervention with 9 Arab-American teens; Pilot Clinic (N = 44)
      determined the characteristics of the accessible teen health clinic population;
      and Pilot School (N = 119) obtained tobacco use data only. RESULTS: From Pilot
      Focus seven themes (being cool, "nshar ma'a al shabab" [hanging out with the
      guys], present [time] orientation, smoking feels and tastes good, keeps your mind
      off trouble, easy to get, and (many) "barriers to quitting") emerged from the
      data. In the Pilot Intervention a 37.5% cessation rate was found. In the Pilot
      Clinic study, 24% males and 17% females smoked. The current smoking rate in the
      Pilot School (N = 119) sample was 17%; 34% admitted to having ever smoked (even a
      puff). Significant predictors for current tobacco use included poor grades,
      stress, having many family members and peers who smoke, being exposed to many
      hours of smoking each day, receiving offers of tobacco products, advertising and
      mail, and believing that tobacco can help one to make friends. CONCLUSIONS: The
      four pilots contributed unique and essential knowledge for designing a
      longitudinal clinical trial on tobacco use by Arab-American adolescents.

PMID- 14572434
TI  - Opportunities for oral cancer screening among older African-American women.
AB  - BACKGROUND: Older persons with smoking histories are important targets for oral
      cancer screening. Although older persons in low-income communities often lack
      regular dental care, little is known about the characteristics of groups at
      greatest risk for poor screening. METHODS: Survey data from 576 African-American
      women aged 45-93 were used to identify predictors of smoking and recency and type
      of dental care. RESULTS: Fifty-nine percent of respondents were current or former
      smokers, and 62% reported dental care within the past 3 years. Among smokers, no
      recent dental care was associated with older age, worse health, not working, no
      regular medical provider, and no recent mammography. CONCLUSIONS: These results
      suggest that episodic visits to non dentist providers offer opportunities for
      oral screening in high-risk populations.

PMID- 14572435
TI  - Breast cancer and the uptake of mammography screening services by women with
      intellectual disabilities.
AB  - BACKGROUND: It is estimated that approximately 50% of women in Australia with
      intellectual disability will live to 70 years of age and as a result many will
      fall within the age group at highest risk for breast cancer (50-69 years).
      METHODS: Subjects were identified through the Western Australia Disability
      Services database. To determine the number of women diagnosed with breast cancer
      during the period 1982-2000, individual records (n = 2,370) were linked to the
      Western Australia Cancer Registry and the Mammography Screening Registry.
      RESULTS: The incidence of breast cancer among women with intellectual disability
      was 64.0 per 100,000 person-years, by comparison with 146.7 per 100,000 person
      years in the general population. The uptake of breast cancer screening was
      examined in a subgroup of 380 women, 34.7% of whom had used mammographic
      screening, as opposed to 54.6% screening uptake in the general population.
      Failure to use screening services was highest in women who were unmarried, and
      was positively associated with severity of intellectual disability, presence of
      physical disabilities, and urban residence. CONCLUSIONS: The lower incidence of
      breast cancer in women with intellectual disability may in part be attributable
      to decreased life expectancy, but it also appears to reflect significant under
      utilization of the readily available screening services.

PMID- 14572436
TI  - Accuracy of self-reports of fecal occult blood tests and test results among
      individuals in the carpentry trade.
AB  - BACKGROUND: Inaccuracy in self-reports of colorectal cancer (CRC) screening
      procedures (e.g., over- or underreporting) may interfere with individuals
      adhering to appropriate screening intervals, and can blur the true effects of
      physician recommendations to screen and the effects of interventions designed to
      promote screening. We assessed accuracy of self-report of having a fecal occult
      blood test (FOBT) within a 1-year window based on receipt of FOBT kits among
      individuals aged 50 and older in the carpentry trade (N = 658) who were off
      schedule for having had a FOBT. METHOD: Indices of evaluating accuracy of self
      reports (concordance, specificity, false-positive and false-negative rates) were
      calculated relative to receipt of a mailed FOBT. Among those who mailed a
      completed FOBT, we assessed accuracy of reporting the test result. RESULTS:
      Participants underestimated having performed a FOBT (false-negative rate of 44%).
      Accuracy was unrelated to perceptions of getting or worrying about CRC or family
      history. Self-reports of having a negative FOBT result more consistently matched
      the laboratory result (specificity 98%) than having a positive test result
      (sensitivity 63%). CONCLUSIONS: Contrary to other findings, participants under-
      rather than over reported FOBT screening. Results suggest greater efforts are
      needed to enhance accurate recall of FOBT screening.

PMID- 14572437
TI  - Associations between recommended levels of physical activity and health-related
      quality of life. Findings from the 2001 Behavioral Risk Factor Surveillance
      System (BRFSS) survey.
AB  - BACKGROUND: Although the benefits of regular physical activity on morbidity and
      mortality are established, relationships between recommended levels of physical
      activity and health-related quality of life (HRQOL) have not been described. The
      authors examined whether recommended levels of physical activity were associated
      with better HRQOL and perceived health status. METHODS: Using data from 175,850
      adults who participated in the 2001 Behavioral Risk Factor Surveillance System
      survey, the authors examined the independent relationship between recommended
      levels of moderate or vigorous physical activity and four measures of HRQOL
      developed by the U.S. Centers for Disease Control and Prevention. Multivariate
      logistic regression was used to obtain odds ratios (ORs) and 95% confidence
      intervals (CIs) adjusted for age, race/ethnicity, sex, education, smoking status,
      and body mass index. RESULTS: The proportion of adults reporting 14 or more
      unhealthy days (physical or mental) was significantly lower among those who
      attained recommended levels of physical activity than physically inactive adults
      for all age, racial/ethnic, and sex groups. After multivariate adjustment, the
      relative odds of 14 or more unhealthy days (physical or mental) in those with the
      recommended level of activity compared to physically inactive adults was 0.67
      (95% CI: 0.60, 0.74) for adults aged 18-44 years, 0.40 (95% CI: 0.36, 0.45) for
      adults aged 45-64 years, and 0.41 (95% CI: 0.36, 0.46) for adults aged 65 years
      or older. The results persist even among adults with a chronic condition such as
      arthritis. CONCLUSIONS: These results highlight the need for health programs to
      increase participation in regular physical activity.

PMID- 14572438
TI  - Is restricting tobacco sales the answer to adolescent smoking?
AB  - Enforcement of legislation restricting retail access to tobacco is increasingly
      relied on to reduce adolescent smoking rates. In 1996, health authorities in the
      Northern Sydney Health Area began monitoring tobacco retailer compliance (PROOF
      program) with staged purchase attempts by adolescents below the legal age (18
      years). Repeat cross-sectional surveys before (1995) and after (2000) the
      introduction of PROOF monitored changes in adolescent smoking behaviour. Students
      aged 12 to 17 years from 11 Northern Sydney metropolitan public secondary schools
      were surveyed for self-reported smoking and tobacco purchasing behavior in 1995
      (n = 5,206) and 2000 (n = 4,120). Between 1996 and 2000, 545 retailer compliance
      checks found 34% unlawfully sold cigarettes to minors and 28% of these repeated
      the offence. Nine prosecutions resulted. Modelling revealed a significant
      association between the intervention and never having smoked (adjusted OR = 1.16,
      95% CI = 1.01-1.33) although there was no significant association with being a
      current smoker. The odds of being a smoker were greater for students from
      coeducational schools, with this effect being modified by gender. There was no
      reduction in adolescent smoking with active enforcement of tobacco access laws
      despite an apparent increase in students who reported never to have smoked.

PMID- 14572439
TI  - Insulin-like growth factor-I improves cerebellar dysfunction but does not prevent
      cerebellar neurodegeneration in the calcium channel mutant mouse, leaner.
AB  - The effects of insulin-like growth factor-I (IGF-I) on cerebellar dysfunction and
      neurodegeneration were investigated in leaner mice, which exhibit cerebellar
      ataxia and neurodegeneration related to P/Q-type calcium channel mutations.
      Leaner mice showed significantly reduced serum and cerebellar IGF-I
      concentrations compared to wild-type mice at postnatal day 30. Behavioral
      assessment of leaner mice injected with IGF-I subcutaneously for 4 weeks showed
      partially improved cerebellar function. Histological analysis of IGF-I treated
      leaner cerebella showed no difference in the number of dying Purkinje cells
      compared to control leaner cerebella. These results further support potential use
      of IGF-I as a therapeutic aid for cerebellar ataxia related to calcium channel
      mutations. Nonetheless, IGF-I administration does not rescue dying cerebellar
      neurons, which suggests that the beneficial effects of IGF-I may have been
      achieved through surviving cerebellar neurons.

PMID- 14572440
TI  - Identification of novel genes and altered signaling pathways in the retinal
      pigment epithelium during the Royal College of Surgeons rat retinal degeneration.
AB  - Shed photoreceptor outer segments (POS) are phagocytosed by RPE cells in a
      circadian manner. The homozygous deletion of the c-mer gene abolishes the
      ingestion phase of this phagocytosis in the Royal College of Surgeons (RCS) rat
      strain, which in turn leads to the death of photoreceptor cells. We identified
      RPE transcripts for which the expression is modulated by the abrogation of POS
      phagocytosis. A microarray approach and the differential display (DDRT-PCR)
      technique revealed 116 modulated known genes, 4 modulated unknown genes, and 15
      expressed sequenced tags (ESTs) corresponding to unknown genes. The microarray
      and DDRT-PCR analyses detected alterations in signaling pathways such as the
      phosphatidylinositol 3-kinase-Akt-mTOR pathway and the DLK/JNK/SAPK pathway. The
      abrogation of POS phagocytosis caused a decrease in endomembrane biogenesis and
      altered endocytosis, exocytosis, transcytosis, and several metabolic and
      signaling pathways in RCS RPE cells. We also found differential levels of
      transcripts encoding proteins involved in phagocytosis, vesicle trafficking, the
      cytoskeleton, retinoic acid, and general metabolism.

PMID- 14572441
TI  - Thrombin induces nigral dopaminergic neurodegeneration in vivo by altering
      expression of death-related proteins.
AB  - One week after intranigral injection of thrombin resulted in a dose-dependent
      loss of dopaminergic neurons (20-78%) in the rat substantia nigra (SN), as
      evidenced by tyrosine hydroxylase (TH) immunohistochemistry. This cell death was
      accompanied by localization of terminal deoxynucleotidyl transferase-mediated
      fluorecein UTP nick end labeling (TUNEL) staining within dopaminergic neurons,
      activation of caspase-3 and attenuation of dopaminergic neuronal cell death in
      the SN by the caspase inhibitor (zVAD-fmk), indicative of apoptosis. Furthermore,
      Western blot analyses and double-immunofluorescent staining showed activation of
      c-Jun N-terminal kinase (JNK) and p53, and a localization of p53 in the
      dopaminergic neurons in the SN after thrombin, respectively. Intriguingly,
      Western blot analyses demonstrated significant down-regulation of Bcl-2 protein,
      but no alteration in Bax protein expression in the SN after thrombin. Consistent
      with in vivo data, degeneration of dopaminergic neurons and colocalization of
      TUNEL and TH were observed in mesencephalic cultures, following treatment with
      thrombin. Cell death was almost completely abolished by the thrombin-specific
      inhibitor, hirudin. Thrombin receptor-activating peptides (TRAP-6 and-14) did not
      mimic the effects of thrombin, even at much higher (1,000 to 2,000-fold)
      concentrations, although expression of protease-activated receptor-1 (PAR-1) mRNA
      was detected using RT-PCR. Morphological evidence and molecular events in vivo
      and in vitro collectively suggest that thrombin induces apoptosis in dopaminergic
      neurons via non-PAR-1 receptors.

PMID- 14572442
TI  - Functional gamma-secretase complex assembly in Golgi/trans-Golgi network:
      interactions among presenilin, nicastrin, Aph1, Pen-2, and gamma-secretase
      substrates.
AB  - Gamma-secretase is a proteolytic complex whose substrates include Notch, beta
      amyloid precursor protein (APP), and several other type I transmembrane proteins.
      Presenilin (PS) and nicastrin are known components of this high-molecular-weight
      complex, and recent genetic screens in invertebrates have identified two
      additional gene products, Aph1 and Pen-2, as key factors in gamma-secretase
      activity. Here, we examined the interaction of the components of the gamma
      secretase complex in Chinese hamster ovary cells stably expressing human forms of
      APP, PS1, Aph1, and Pen-2. Subcellular fractionation of membrane vesicles and
      subsequent coimmunoprecipitation of individual gamma-secretase components
      revealed that interactions among all proteins occurred in the Golgi/trans-Golgi
      network (TGN) compartments. Furthermore, incubation of the Golgi/TGN-enriched
      vesicles resulted in de novo generation of amyloid beta-protein and APP
      intracellular domain. Immunofluorescent staining of the individual gamma
      secretase components supported our biochemical evidence that the gamma-secretase
      components assemble into the proteolytically active gamma-secretase complex in
      the Golgi/TGN compartment.

PMID- 14572443
TI  - TCH346 prevents motor symptoms and loss of striatal FDOPA uptake in bilaterally
      MPTP-treated primates.
AB  - The neuroprotective efficacy of the propargylamine TCH346 was studied in the
      primate model of Parkinson's disease, the bilaterally MPTP-treated monkey. Male
      rhesus monkeys received 2.5 mg MPTP into the left carotid artery and, 8 weeks
      later, 1.25 mg MPTP into the right carotid artery. Starting 2 h after the second
      MPTP infusion, either 0.014 mg/kg TCH346 or its solvent was subcutaneously
      injected twice per day for 14 days. The first MPTP treatment induced mild
      Parkinson symptoms, reduced right limb movements, and reduced FDOPA uptake in the
      left striatum. The second MPTP treatment made Parkinson symptoms worse, reduced
      left limb movements, and reduced FDOPA uptake in the right striatum of solvent
      treated monkeys. In contrast, the second MPTP treatment did not further worsen
      motor symptoms and did not decrease FDOPA uptake in the right striatum of TCH346
      treated monkeys. Although the effects of the second MPTP treatment were largely
      prevented, the effects of the first MPTP treatment were not reversed by TCH346.
      Immunohistochemical examination confirmed the dramatic loss of dopamine cells in
      vehicle-treated monkeys and the preservation of these neurons in the right brain
      side of the TCH346-treated animals. In conclusion, systemic administration of
      TCH346 prevented motor symptoms and nigrostriatal degeneration induced by MPTP in
      primates.

PMID- 14572444
TI  - Behavioral changes are not directly related to striatal monoamine levels, number
      of nigral neurons, or dose of parkinsonian toxin MPTP in mice.
AB  - Behavioral analyses of mice intoxicated by the parkinsonian toxin 1-methyl-4
      phenyl-1,2,3,6,-tetrahydropyridine (MPTP) have generated conflicting results. We
      therefore analyzed the relationship between behavioral changes, loss of monoamine
      levels, and loss of dopaminergic cell bodies in groups of mice intoxicated with
      acute or subchronic MPTP protocols. Despite a higher degree of neuronal loss in
      the mice intoxicated using subchronic protocols, dopamine loss was severe and
      homogeneous in the striatum in all groups. Dopamine levels were less severely
      reduced in the frontal cortex in the three groups of MPTP-intoxicated mice.
      Norepinephrine and serotonin levels in the striatum were decreased only in the
      mice intoxicated with the acute protocol. The most surprising result was that the
      mice intoxicated with the subchronic protocols were more active than the saline
      treated mice. As reported in rats with dopamine depletion in the prefrontal
      cortex, the hyperactivity observed in our mice could be due to the reduced
      dopamine levels detected in this structure.

PMID- 14572445
TI  - Extrajunctional resting Ca2+ influx is not increased in a severely dystrophic
      expiratory muscle (triangularis sterni) of the mdx mouse.
AB  - Freshly isolated adult mdx and nondystrophic (C57B110SnJ) muscle fibers were used
      to examine the potential role of resting Ca2+ influx in the pathogenesis of
      Duchenne and related dystrophies. Microfluorimetric determinations of resting
      divalent cation influx were obtained from undissociated intact muscle fibers in
      the triangularis sterni (TS), a thin expiratory muscle. Morphological evidence
      indicated severe dystrophic alterations in the mdx TS at 5 months, and a
      pronounced loss of fibers with connective tissue infiltration in older animals.
      To examine resting Ca2+ influx, fibers were loaded with FURA PE3 and the rate of
      quenching of intracellular signal following the extracellular addition of Mn2+
      was determined from extrajunctional regions. There was no significant difference
      in quench rate between nondystrophic and mdx TS fibers. These results indicate
      that severe dystrophic pathology in the absence of dystrophin is not due to
      generalized increases in resting Ca2+ influx.

PMID- 14572447
TI  - Pin1 colocalization with phosphorylated tau in Alzheimer's disease and other
      tauopathies.
AB  - Pin1, a peptidyl-prolyl isomerase binds to mitotic serine or threonine
      phosphoproteins. In Alzheimer's disease (AD) evidence points to the reactivation
      of mitosis in vulnerable neurons. Tangles composed of hyperphosphorylated tau
      contain phosphorylated Thr231 (pThr231 tau), which occurs to a greater extent in
      the AD brain than in the normal brain, and Pin1 has been shown to bind pThr231
      tau. Here, Pin1 distribution in AD, and its colocalization with pThr231 tau in
      AD, FTDP-17 (P301L), Pick's disease (PiD), and PSP was investigated using TG-3, a
      monoclonal antibody to conformationally altered pThr231 tau. The Pin1 antibody A
      20 detected granular Pin1 staining in AD brains, but not in normal brains. A-20
      immunoreactive granules colocalized with TG-3-stained granules but not with TG-3
      stained pretangles, tangles, or Pick bodies in AD, PiD, and FTDP-17 (P301L). Pin1
      granules were sparse in PSP, and rarely did A-20 colocalize with TG-3. The
      appearance of Pin1 granules in the early stages of AD, PiD, and FTDP-17 (P301L)
      implicates Pin1 in their pathogenesis but not in PSP.

PMID- 14572446
TI  - DNA microarray analysis of functionally discrete human brain regions reveals
      divergent transcriptional profiles.
AB  - Transcriptional profiles within discrete human brain regions are likely to
      reflect structural and functional specialization. Using DNA microarray
      technology, this study investigates differences in transcriptional profiles of
      highly divergent brain regions (the cerebellar cortex and the cerebral cortex) as
      well as differences between two closely related brain structures (the anterior
      cingulate cortex and the dorsolateral prefrontal cortex). Replication of this
      study across three independent laboratories, to address false-positive and false
      negative results using microarray technology, is also discussed. We find greater
      than a thousand transcripts to be differentially expressed between cerebellum and
      cerebral cortex and very few transcripts to be differentially expressed between
      the two neocortical regions. We further characterized transcripts that were found
      to be specifically expressed within brain regions being compared and found that
      ontological classes representing signal transduction machinery, neurogenesis,
      synaptic transmission, and transcription factors were most highly represented.

PMID- 14572448
TI  - Histopathological alterations and functional brain deficits after transient
      hypoxia in the newborn rat pup: a long term follow-up.
AB  - To assess temporal brain deficits consecutive to severe birth hypoxia, newborn
      rats were exposed for 20 min to 100% N2. This treatment induced a long-term
      growth retardation and a delayed, but only transient, neuronal loss
      (approximately 25%) in the CA1 hippocampus and parietal cortex, starting from 3
      days and peaking at 6 days post-hypoxia. The expression profiles of various
      apoptosis-regulating proteins (including Bcl-2, Bax, p53 and caspase-3) were well
      correlated to the alterations of nuclear morphology depicted by 4,6-diamidino-2
      phenylindole (DAPI). Whereas they confirmed a gradual histological recovery,
      specific DNA fragmentation patterns suggested that birth hypoxia may transiently
      reactivate the developmental programme of neuronal elimination. Although they
      successfully achieved various behavioral tests such as the righting reflex,
      negative geotaxis, locomotor coordination, and the eight-arm maze tasks, both
      developing and adult hypoxic rats were repeatedly slower than controls,
      suggesting that birth hypoxia is associated to moderate but persistent
      impairments of functional capacities.

PMID- 14572449
TI  - Expression of ICAM-1, TNF-alpha, NF kappa B, and MAP kinase in tubers of the
      tuberous sclerosis complex.
AB  - Individuals affected with tuberous sclerosis complex (TSC) develop cortical
      tubers characterized by disorganized cytoarchitecture and morphologically
      abnormal cell types, such as dysplastic neurons (DNs) and giant cells (GCs). As
      part of ongoing cDNA array analysis to study the molecular pathogenesis of tuber
      formation, we detected increased expression of intercellular adhesion molecule-1
      (ICAM-1) mRNA, a cell adhesion molecule (CAM) that functions in cytokine
      signaling, in tubers. Western and immunohistochemical analyses revealed that ICAM
      1 protein was selectively expressed in tubers, but was only minimally expressed
      in control cortex, adjacent nontuberal cortex, or in non-TSC focal cortical
      dysplasia. Increased expression of ICAM-1 was found in mice in which the Tsc1
      gene was conditionally inactivated in astrocytes. Expression of molecules
      involved in ICAM-1 activation and cytokine signaling were increased in tubers,
      including tumor necrosis factor alpha (TNF-alpha), mitogen activated protein
      kinase (MAPK), and nuclear factor kappa B (NF-kappaB). Numerous CD68
      immunoreactive macrophages were observed clustered around GCs further supporting
      an inflammatory response in tubers. Expression of caspase 8 and Fas support
      cytokine activation and detection of TUNEL reactivity suggests ongoing cell death
      in tubers. Specific alterations in ICAM-1, TNF-alpha, NF-kappaB1, and MAPK
      expression coupled with the detection of numerous CD68-immunoreactive macrophages
      suggests activation of proinflammatory cytokine signaling pathways in tubers that
      may culminate in cell death.

PMID- 14572451
TI  - The signaling components of sensory fiber transmission involved in the activation
      of ERK MAP kinase in the mouse dorsal horn.
AB  - The stimulation of C-fiber sensory neurons is known to induce activation of the
      ERK MAP kinase signaling pathway in the spinal cord dorsal horn. In this study we
      have elucidated some of the signaling components of C-fiber transmission
      responsible for ERK activation. Using an in vitro slice preparation of the mouse
      spinal cord dorsal horn, we compared the release of substance P (SP) and BDNF
      with the activation of ERK in postsynaptic neurons. We observed that primary
      afferent stimulation recruiting C-fibers was required for both SP and BDNF
      release and ERK activation in post-synaptic dorsal horn neurons. Glutamate
      transmission via NMDA and mGluR1 but not AMPA receptors was critical to this ERK
      activation. BDNF signaling via TrkB receptors but not SP signaling via NK(1) were
      also involved in ERK recruitment. In conclusion, glutamate and BDNF are the
      important C-fiber signaling components for ERK activation in dorsal horn neurons.

PMID- 14572450
TI  - Dehydroepiandrosterone reduces expression and activity of BACE in NT2 neurons
      exposed to oxidative stress.
AB  - Recently, we showed that oxidative stress activates the expression and activity
      of the beta-site AbetaPP-cleaving enzyme (BACE), an aspartyl protease responsible
      for the beta-secretase cleavage of AbetaPP. The identification of compounds able
      to prevent the induction of this event is an important goal of therapeutic
      strategies for Alzheimer's disease (AD). Dehydroepiandrosterone (DHEA) is an
      adrenal steroid that improves a variety of functions in the central nervous
      system. Moreover, a series of evidence suggests that DHEA displays antioxidant
      properties in different experimental models. In the present paper we show that
      pretreatment with DHEA is able to rescue the increase of mRNA expression, protein
      levels, and activity of BACE, produced by oxidative stress in NT2 neurons. BACE,
      being the enzyme that initiates the production of Abeta, is a drug target for AD.
      Our results imply that DHEA administration may slow down the AD pathological
      process, lowering Abeta accumulation.

PMID- 14572452
TI  - Recognition molecule associated carbohydrate inhibits postsynaptic GABA(B)
      receptors: a mechanism for homeostatic regulation of GABA release in perisomatic
      synapses.
AB  - Extracellular matrix molecules are important cues in the shaping of nervous
      system structure and function. Here, we describe a novel mechanism by which the
      HNK-1 carbohydrate carried by recognition molecules regulates perisomatic
      inhibition in the hippocampus. Neutralization of HNK-1 activity by an HNK-1
      antibody results in GABA(B) receptor-mediated activation of K(+) currents in CA1
      pyramidal cells, which elevates extracellular K(+) concentration and reduces
      evoked GABA release in perisomatic inhibitory synapses. This mechanism is
      supported by pharmacological analysis in hippocampal slices and data showing that
      the HNK-1 carbohydrate binds to GABA(B) receptors and inhibits GABA(B) receptor
      activated K(+) currents in a heterologous expression system. We suggest that the
      HNK-1 carbohydrate is involved in homeostatic regulation of GABA(A) receptor
      mediated perisomatic inhibition by suppression of postsynaptic GABA(B) receptor
      activity.

PMID- 14572453
TI  - Adaptor protein complex-4 (AP-4) is expressed in the central nervous system
      neurons and interacts with glutamate receptor delta2.
AB  - Ion channels and receptors are targeted and localized at specific postsynaptic
      sites to mediate neurotransmission. Receptors clustering at postsynaptic sites
      has been extensively studied; however, the molecular mechanisms underlying
      intracellular trafficking of receptors to their specific destinations remain
      unclear. In the present study, we found that glutamate receptor delta2 interacted
      directly with AP-4, a newly identified adaptor protein complex-4 that mediates
      protein sorting in mammalian cells. The interaction between mu4 subunit of AP-4
      and the delta2 C-terminal involved multiple amino acid sequence motifs other than
      the classical tyrosine-based signals. AP-4 complex is expressed ubiquitously in
      many regions of brain, with localization on the Golgi-like structures in the cell
      bodies and dendrites of neurons. In addition, overexpression of mu4 substantially
      altered the distribution pattern of delta2 in heterologous cells. These results
      suggest a potential involvement of AP-4 in the trafficking of delta2 in the
      brain.

PMID- 14572454
TI  - No barrier to diffusion between cell soma and neurite membranes in sympathetic
      neurons for a GPI-anchored glycoprotein.
AB  - As neurons extend their axons, it is thought that newly synthesised membrane
      components travel in vesicles along the axon, fuse with the growth cone membrane,
      and diffuse back along the axonal membrane. However, it is difficult to explain
      how axons continue to be populated with membrane proteins as they extend in
      length. To investigate this problem, we have used a CEPU-green fluorescent
      protein (GFP) chimeric protein to study the site of insertion of new glycosyl
      phosphatidyl inositol (GPI)-anchored glycoproteins and their subsequent behaviour
      in chick dorsal root ganglia (DRG) neurons. Infection of cultures grown for 24 h
      revealed rapid expression of CEPU-GFP over the whole surface of the neuron, more
      rapidly than could be accounted for by diffusion from the growth cone, and
      fluorescence intensity was uniform along the length of the neurite.
      Photobleaching experiments of neurite membrane revealed that recovery of
      fluorescence was due to diffusion from adjacent membranes and there was no
      evidence for membrane flow in either direction. Photobleaching of membrane
      adjacent to the cell body also showed rapid recovery, with chimera diffusing both
      from cell body membrane and the distal neurite membrane into the bleached area.
      These results suggest there is no barrier to diffusion between the cell body and
      neurite membrane in DRG and sympathetic neurons cultured for 1 or 2 days in
      vitro. We propose that the neurite is populated by newly synthesised chimera by
      diffusion from both regions. This situation may also occur in neurons in the
      early stages of extending axons in vivo prior to polarisation and the development
      of the dendritic field.

PMID- 14572455
TI  - Regulation, cellular localization, and function of the p75 neurotrophin receptor
      (p75NTR) during the regeneration of facial motoneurons.
AB  - The common neurotrophin receptor (p75NTR) is a member of the tumor necrosis
      factor receptor superfamily and binds the neurotrophins nerve growth factor,
      brain derived neurotrophic factor, neurotrophin-3, and neurotrophin-4. P75NTR is
      expressed on developing motoneurons and is reexpressed on adult motoneurons under
      pathological conditions such as nerve trauma or neurodegeneration. Here we
      examined the regulation and function of p75NTR during regeneration after
      peripheral transection of the facial nerve of adult mice. Axotomy led to a strong
      increase in p75NTR immunoreactivity on the injured and regenerating facial
      motoneurons and on denervated Schwann cells. Cellular colocalization also
      revealed p75NTR immunoreactivity on neighboring blood vessels and cells in the
      injured nerve, but not on activated GFAP+ astrocytes or alphaMbeta2+ microglia
      and macrophages. To determine the function of this receptor we examined the
      effects of p75NTR deficiency on neuroglial activation, on the speed of axonal
      regeneration, and on neuronal survival after facial axotomy in two different
      transgenic mouse lines carrying targeted insertions exon 4 (p75e4-/-) or exon 3
      (p75e3-/-) of the p75NTR gene. In both animal models absence of p75NTR led to a
      twofold, early increase in the number of CD3+. T-cells and in the microglial
      immunoreactivity for the alpha5beta1, alpha6beta1, and alphaMbeta2 integrins at
      day 4 in the facial nucleus and in the crushed facial motor nerve. No changes
      were observed in the number of reactive GFAP+ astrocytes or on late microglial
      and lymphocyte responses. The rate of axonal elongation in the crushed facial
      nerve, as well as neuronal survival, was found to be unaffected. Overall, the
      current study shows that the p75NTR receptor plays an important regulatory role
      in early neuroglial and immune activation.

PMID- 14572456
TI  - Cell cycle events distinguish sensory neuronal death from motoneuron death as a
      result of trophic factor deprivation.
AB  - The clarification of mechanisms of developmental cell death may provide hints in
      the prevention of pathological neuronal death. The execution phase of cell death
      has been extensively characterized; however, events that occur prior to this
      phase are less well understood. Previous studies have suggested that terminally
      differentiated neurons induced to die in various experimental paradigms may be
      making an abortive attempt to reenter the cell cycle. We have examined this
      process in postmitotic motoneurons and dorsal root ganglia sensory neurons in the
      developing chick embryo in vitro and in vivo. An examination of the programmed
      cell death of postmitotic motoneurons does not implicate a role for cell cycle
      related proteins. We did, however, observe a decrease in the amount of cell death
      in dorsal root ganglion cells of embryos treated with cell cycle inhibitors.
      These results indicate that upstream initiators of the neuronal cell death
      pathway vary between phenotypes.

PMID- 14572457
TI  - Brain-derived neurotrophic factor upregulates and maintains AMPA receptor
      currents in neocortical GABAergic neurons.
AB  - The regulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)
      type glutamate receptors is implicated in synaptic plasticity. Although we have
      found that brain-derived neurotrophic factor (BDNF) triggers surface
      translocation of AMPA receptor proteins, the physiological significance of the
      BDNF effect remained to be determined. The present immunohistochemical studies
      revealed that cortical GABAergic neurons exhibited the most striking response to
      BDNF. Accordingly, we monitored AMPA-triggered currents through GABAergic
      neurons: Chronic BDNF treatment increased the AMPA-triggered currents but not
      NMDA-triggered currents in culture. In parallel, the amplitude, but not
      frequency, of spontaneous miniature excitatory postsynaptic currents (mEPSCs) was
      elevated in GABAergic neurons. In agreement, BDNF enhanced GABA release triggered
      by AMPA compared to the amount triggered by high potassium. Conversely, there was
      a significant decrease in the mEPSC amplitude of GABAergic neurons in
      heterozygous BDNF-knockout mice. These findings indicate that the neurotrophin
      enhances the input sensitivity of GABAergic neurons to facilitate their
      inhibitory function in the neocortex.

PMID- 14572458
TI  - Differential modulation of Kv4 kinetics by KCHIP1 splice variants.
AB  - The beta-subunits of the KChIP family modulate properties and expression level of
      Kv4 channels. We report the cloning of the first splice variant of KChIP1
      (KChIP1b) which contains an extra exon, rich in aromatic residues, in the amino
      terminus. Both splice variants interacted equally well with Kv4.2 subunits based
      on confocal imaging and upregulation of current density (more than five-fold). No
      effects on the voltage dependence of activation or inactivation were noted.
      However, the effects on the kinetics of recovery from inactivation were opposite:
      KChIP1b induced a slow component in the recovery (tau approximately 1.2 s), in
      contrast to the increased recovery rate (tau = 125 ms) with KChIP1a. Accordingly,
      frequency-dependent accumulation of inactivation was enhanced by KChIP1b but
      reduced by KChIP1a. Since Kv4.2 channels are involved in protection against back
      propagating action potentials in dendritic spines, a differential expression of
      either splice variant could shape the dendritic function.

PMID- 14572459
TI  - A role of P301L tau mutant in anti-apoptotic gene expression, cell cycle and
      apoptosis.
AB  - In exploring the causative role of the most common Pro(301)-to-Leu (TauP301L) tau
      missense mutation associated with neurodegenerative tauopathies, we examined
      TauP301L-mediated apoptotic cell death and the expression of a cluster of genes
      involved in the inhibition of apoptosis (IAPs) in human neuroblastoma SH-SY5Y
      cells. Our research found that the expression of TauP301L, but not wild-type tau,
      down regulated the expression of IAPs, including survivin, which plays a role in
      the mitotic spindle checkpoint. The inhibition of IAPs coincided with the
      activation of the pro-apoptotic caspase 3, but preceded apoptotic cell death by
      TUNEL. Furthermore, TauP301L altered the expression of the cell cycle regulatory
      proteins and induced the cell cycle arrest at G(2)/M phase. Our studies
      demonstrate that TauP301L downregulates the expression of genes that protect
      against apoptosis and regulate cell cycle progression. These results suggest a
      novel mechanism of apoptotic cell death in TauP301L-expressing cells that
      involves survivin-mediated activation of cell cycle checkpoint.

PMID- 14572460
TI  - Insert-containing neurotrophins in teleost fish and their relationship to nerve
      growth factor.
AB  - Some teleost species express neurotrophins not known in other vertebrates, namely
      neurotrophin-6 (NT-6) and neurotrophin-7 (NT-7). Mature proteins of both genes
      are closely related to nerve growth factor (NGF). We have cloned zebrafish NGF
      (zNGF) and show that genomic organization and transcript structure of zNGF, zNT
      7, and mouse NGF are highly similar. This suggests the vital importance of
      hitherto unrecognized untranslated regions and principal features of gene
      structure, retained in species separated 410 mya. Aiming to clarify the relation
      between NT-6 and NT-7, we have identified partial NGF and NT-6/7 sequences of
      additional teleost species and a complete set of neurotrophins in two pufferfish
      genomes (fugu and tetraodon). Interestingly, this includes neurotrophin-4/5,
      hitherto not described in any fish species. Identification of only one NT-6/7
      like gene in pufferfish and salmon, phylogenetic analysis and a strikingly high
      identity of an untranslated sequence of zNT-7 and the pufferfish NT-6/7 genes
      strongly suggest that these genes have evolved from a common ancestor after a
      single "fish specific" duplication of NGF. Evidence for sub- and
      neofunctionalization is provided.

PMID- 14572461
TI  - MMP-9 deficiency affects axonal outgrowth, migration, and apoptosis in the
      developing cerebellum.
AB  - Matrix metalloproteinases (MMPs) are responsible for the extensive extracellular
      proteolysis that plays a central role in regulating the pericellular environment,
      contributing to morphogenesis and developmental remodeling. In the CNS, there is
      increasing in vitro evidence for the involvement of MMPs in neurite elongation
      and axonal guidance. Here, we show that expression of MMP-9 is spatiotemporally
      related to cerebellar granule cell migration during postnatal development. Using
      cerebellar explant cultures, we demonstrated that a specific MMP-9-blocking
      antibody affects granular cell axonal outgrowth and migration in a dose-dependent
      manner. In addition, the in vivo analysis of MMP-9-deficient mice revealed
      abnormal accumulation of granular precursors (GPs) in the external granular layer
      (EGL) at a time when migration is normally extensive. Furthermore, GP migration
      was delayed and their programmed cell death was reduced in MMP-9-deficient mice,
      suggesting that MMP-9 is involved in the control of granule cell migration and
      apoptosis. These results provide direct evidence for a physiological role of MMP
      9 in neuronal precursor migration and apoptosis in the developing cerebellum, and
      emphasize the importance of MMP-9 in the temporal regulation of the cerebellar
      microenvironment.

PMID- 14572462
TI  - Redundant functions but temporal and regional regulation of two alternatively
      spliced isoforms of semaphorin 3F in the nervous system.
AB  - SEMA3F is a secreted semaphorin that affects axon and cell guidance in the
      developing nervous system, and is also thought to have anti-tumor activity. Two
      spliced forms of SEMA3F have been identified that differ by the insertion of 31
      amino acids in the sema domain. Here, we investigated the bioactivity of these
      isoforms and show, using coculture and binding assays, that they share common
      axonal chemorepulsive properties and binding to neuropilin receptors. SEMA3F
      isoforms were also found to regulate endothelial cell morphology by remodeling
      lamellipodial protrusions. Although Sema3F expression globally decreased during
      mouse development, we noted an enrichment of the longest isoform at postnatal
      stages in some territories such as the brainstem and spinal cord. These results
      indicate that although functionally redundant in cell culture assays, Sema3F
      spliced forms are characterized in vivo by a temporal and regional specific
      regulation during maturation of the nervous system.

PMID- 14572463
TI  - Transgenic mice expressing mutant A53T human alpha-synuclein show neuronal
      dysfunction in the absence of aggregate formation.
AB  - Alpha-synuclein was implicated in Parkinson's disease when missense mutations in
      the alpha-synuclein gene were found in autosomal dominant Parkinson's disease and
      alpha-synuclein was shown to be a major constituent of protein aggregates in
      sporadic Parkinson's disease and other synucleinopathies. We have generated
      transgenic mice expressing A53T mutant and wild-type human alpha-synuclein. The
      mutant transgenic protein was distributed abnormally to the axons, perikarya, and
      dendrites of neurons in many brain areas. In electron microscopic immunogold
      studies, no aggregation of alpha-synuclein was found in these mice. However,
      behavior analysis showed a progressive reduction of spontaneous vertical motor
      activity in both mutant lines correlating with the dosage of overexpression. In
      addition, deficits of grip strength, rotarod performance, and gait were observed
      in homozygous PrPmtB mice. Transgenic animals expressing mutant alpha-synuclein
      may be a valuable model to assess specific aspects of the pathogenesis of
      synucleinopathies.

PMID- 14572464
TI  - Lack of p53 delays apoptosis, but increases ubiquitinated inclusions, in
      proteasomal inhibitor-treated cultured cortical neurons.
AB  - Proteasomal dysfunction may contribute to neurodegenerative diseases; however,
      its effects on primary neurons are largely unknown. We have previously reported
      that pharmacological proteasomal inhibition leads to apoptosis and cytoplasmic
      ubiquitinated inclusions in primary rat cortical neurons. In cell lines the
      transcription factor p53 is regulated by the proteasome and in some cases it
      mediates death following proteasomal inhibition. It is unclear, however, if this
      is the case in primary neurons. Here we show in proteasome inhibitor-treated
      cortical neurons an early increase of p53 levels, accompanied by nuclear
      translocation. At later time points p53 is found sequestered within ubiquitinated
      inclusions. Compared to controls, p53-deficient mouse neurons show delayed
      apoptosis, but increased numbers of inclusions, likely secondary to enhanced
      survival. We conclude that p53 plays a role in cortical neuron apoptosis induced
      by proteasomal inhibition and, despite the fact that it localizes to inclusions,
      it is not necessary for their formation.

PMID- 14572465
TI  - The gamma 2 subunit of GABA(A) receptors is required for maintenance of receptors
      at mature synapses.
AB  - The gamma2 subunit of GABA(A) receptor chloride channels is required for normal
      channel function and for postsynaptic clustering of these receptors during
      synaptogenesis. In addition, GABA(A) receptor function is thought to contribute
      to normal postnatal maturation of neurons. Loss of postsynaptic GABA(A) receptors
      in gamma2-deficient neurons might therefore reflect a deficit in maturation of
      neurons due to the reduced channel function. Here, we have used the Cre-loxP
      strategy to examine the clustering function of the gamma2 subunit at mature
      synapses. Deletion of the gamma2 subunit in the third postnatal week resulted in
      loss of benzodiazepine-binding sites and parallel loss of punctate
      immunoreactivity for postsynaptic GABA(A) receptors and gephyrin. Thus, the
      gamma2 subunit contributes to postsynaptic localization of GABA(A) receptors and
      gephyrin by a mechanism that is operant in mature neurons and not limited to
      immature neurons, most likely through interaction with proteins involved in
      trafficking of synaptic GABA(A) receptors.

PMID- 14572466
TI  - Regulation of Bax translocation through phosphorylation at Ser-70 of Bcl-2 by MAP
      kinase in NO-induced neuronal apoptosis.
AB  - The molecular mechanism of Bcl-2 phosphorylation and its relationship to Bax is
      largely unknown. Here we show that the phosphorylation of Bcl-2 is involved in
      the intracellular translocation of Bax from cytosol to mitochondria in NO-induced
      neuronal apoptosis. We examined how the phosphorylation of Bcl-2 is regulated
      during the apoptosis and found it to be mediated by the activation of p38 and
      ERK, members of the MAPK superfamily. Furthermore, we investigated whether Bcl-2
      phosphorylation affected Bax translocation, using mutant Bcl-2 expression
      vectors. Cortical neuronal cells overexpressing the Bcl-2 mutant S70A (which
      cannot be phosphorylated) prevented the translocation of Bax. In contrast,
      transfection with Bcl-2 (S70D), a constitutively active Bcl-2 mutant, enhanced
      the translocation. Our results suggested that Bcl-2 phosphorylated at Ser-70
      plays a critial role in the translocation of Bax from the cytosol to the
      mitochondria, and this may regulate NO-induced neuronal apoptosis.

PMID- 14572467
TI  - Cloning and characterization of the mouse AP-2 epsilon gene: a novel family
      member expressed in the developing olfactory bulb.
AB  - Members of the mammalian AP-2 transcription factor family have critical
      regulatory roles in many aspects of development and are also implicated in cancer
      progression. Four AP-2 genes have been previously characterized in mouse and
      human, encoding the AP-2alpha, AP-2beta, AP-2gamma, and AP-2delta proteins. Here
      we report the cloning and characterization of the fifth member of the vertebrate
      AP-2 family, AP-2epsilon. The AP-2epsilon protein is very similar to the other
      family members in its DNA binding and dimerization domain and also contains
      conserved proline and aromatic amino acid residues in the activation domain.
      Consistent with these observations, AP-2epsilon can bind to the GC-rich AP-2
      consensus sequence and can dimerize either with itself or with any of the other
      AP-2 proteins. The AP-2epsilon protein is also able to activate transcription in
      a binding site-dependent manner. However, the mouse AP-2epsilon gene is
      distinctive from the other AP-2 genes in its pattern of expression during
      embryogenesis. Unlike AP-2alpha, AP-2beta, and AP-2gamma, transcripts
      corresponding to AP-2epsilon are not found in the neural crest and its
      derivatives. Instead, AP-2epsilon is expressed most prominently in the mitral
      cell layer of the developing olfactory bulb. A comparison of AP-2 gene family
      expression in the olfactory system suggests both distinct and overlapping
      functions for these transcription factors in forebrain development.

PMID- 14572468
TI  - NG2-expressing glial progenitor cells: an abundant and widespread population of
      cycling cells in the adult rat CNS.
AB  - Glial progenitor cells of the developing CNS committed to the oligodendrocyte
      lineage (OPCs) express the chondroitin sulfate proteoglycan, NG2. A proportion of
      OPCs fail to differentiate past the stage at which they express NG2 and the lipid
      antigen O4 and persist in the adult CNS in a phenotypically immature form.
      However, the physiological function of NG2(+) cells in the adult CNS is unknown.
      Using antibodies against NG2 we show that NG2 is expressed by a distinct cell
      population in the mature CNS with the homogeneous antigenic phenotype of
      oligodendrocyte progenitors. The morphology of NG2(+) OPCs varies from region to
      region, reflecting the different structural environments, but they appear to
      represent a homogeneous population within any one gray or white matter region. A
      study of nine CNS regions showed that NG2(+) OPCs are numerous throughout the CNS
      and numbers in the white matter are only 1.5 times that in the gray. Whereas the
      ratio of OPCs to myelinating oligodendrocytes in the spinal cord gray and white
      matter approximates 1:4, gray matter regions of the forebrain have a 1:1 ratio, a
      phenomenon that will have consequences for oligodendrocyte replacement following
      demyelination. BrdU incorporation experiments showed that NG2(+) cells are the
      major dividing cell population of the adult rat CNS. Since very little apoptosis
      was detected and BrdU became increasingly present in oligodendrocytes after a 10
      day pulse chase, with a concomitant decrease in NG2(+) BrdU incorporating cells,
      we suggest that the size of the oligodendrocyte population may actually increase
      during adult life.

PMID- 14572470
TI  - Estrogen-induced changes in the microtubular system correlate with a decreased
      susceptibility of aging neurons to beta amyloid neurotoxicity.
AB  - A growing body of evidence suggests that estrogen has beneficial effects on
      Alzheimer's disease. However, the mechanisms underlying estrogen's
      neuroprotective effects are not completely understood. In the present study, we
      analyzed first whether estrogen protects mature hippocampal neurons against
      fibrillar Abeta-induced neurotoxicity. 17alpha-Estradiol and 17beta-estradiol
      partially prevented neuronal death induced by fibrillar Abeta. Estrogen-induced
      neuroprotection correlated with the formation of a more dynamic microtubular
      system, including an increase in the pool of unstable microtubules and the
      expression of juvenile microtubule-associated proteins MAP2c and MAP1b. These
      results provide further evidence that experimental conditions capable of
      increasing the pool of unstable microtubules might render mature hippocampal
      neurons resistant to the degeneration caused by fibrillar Abeta deposits.

PMID- 14572469
TI  - Inhibition of CDK5 is protective in necrotic and apoptotic paradigms of neuronal
      cell death and prevents mitochondrial dysfunction.
AB  - Previous studies suggested that pro-apoptotic stimuli may trigger a fatal
      reactivation of cell cycle elements in postmitotic neurons. Supporting this
      hypothesis, small molecule inhibitors of cyclin-dependent kinases (CDKs), which
      are known primarily as cell cycle regulators, are neuroprotective. However,
      available CDK inhibitors cannot discriminate between the different members of the
      CDK family and inhibit also CDK5, which is not involved in cell cycle control.
      Testing a new class of CDK inhibitors, we find that inhibitory activity against
      CDK5, but not cell cycle-relevant CDKs, confers neuroprotection. Moreover, we
      demonstrate that cleavage of the CDK5 activator protein p35 to p25 is associated
      with CDK5 overactivation after focal cerebral ischemia, but not in other models
      used in this study. We find that blocking CDK5 activity, but not caspase
      inhibition, protects mitochondrial integrity of lesioned neurons. Thus, in our
      models, CDK5, rather than cell cycle-relevant CDKs, activates neuronal cell death
      pathways upstream of mitochondrial dysfunction, and inhibition of CDK5 may
      promote functional long-term rescue of injured neurons. Moreover, we present the
      first CDK5-selective small molecule inhibitor, lacking unwanted cytostatic
      effects due to cross-inhibition of mitotic CDKs.

PMID- 14572471
TI  - Two distinct forms of desensitization of G-protein coupled inwardly rectifying
      potassium currents evoked by alkaloid and peptide mu-opioid receptor agonists.
AB  - Mu-opioid receptors (MORs) activate G-protein coupled inwardly rectifying
      potassium (GIRK) channels. The peptide agonist [D-Ala(2), NMe-Phe(4), Gly(5)
      ol]enkephalin (DAMGO), but not the alkaloid morphine (MS), leads to acute
      desensitization of this response. Furthermore, DAMGO, as opposed to MS, triggers
      rapid internalization of MORs. Given this dichotomy, we probed the relationship
      between receptor internalization and GIRK current desensitization in neurons of
      the locus coeruleus (LC) using acute rat brain slices. Interfering with MOR
      recycling by selective impairment of dynamin-dependent endocytosis left GIRK
      current desensitization unchanged. Conversely, coapplication of MS with a low
      concentration of DAMGO, a cocktail reported to enhance MOR internalization,
      revealed competition between the two agonists and normal desensitization. We also
      examined the case of methadone (MD), an alkaloid that has been reported to
      strongly trigger endocytosis. Interestingly, MD and other alkaloids agonists did
      induce GIRK current desensitization, but only at suprasaturating concentrations.
      Furthermore, responses to alkaloids were blunted in LC neurons and the same
      agonists inhibited GIRK currents in cells that do not express MORs. Our results
      indicate that two distinct forms of MOR-evoked GIRK current desensitization
      exist. Peptide agonists induce receptor-mediated desensitization while alkaloid
      agonists lead to apparent desensitization by receptor-independent inhibition of
      GIRK channels.

PMID- 14572472
TI  - Localization of osteopontin in oviduct tissue and eggshell during different
      stages of the avian egg laying cycle.
AB  - The avian eggshell is an acellular bioceramic containing organic and inorganic
      phases that are sequentially assembled during the time the egg moves along the
      oviduct. As it has been demonstrated in other mineralized tissues, mineralization
      of the eggshell is regulated by extracellular matrix proteins especially the
      anionic side chains of proteoglycans. Among them, osteopontin has been found in
      the avian eggshell and oviduct. However, its precise localization in the eggshell
      or in different oviduct regions during eggshell formation, nor its function have
      been established. By using anti-osteopontin antibody (OPN 1), we studied its
      immunolocalization in the isthmus, red isthmus and shell gland of the oviduct,
      and in the eggshell during formation. In the eggshell, osteopontin was localized
      in the core of the non-mineralized shell membrane fibers, in the base of the
      mammillae and in the outermost part of the palisade. In the oviduct, OPN 1 was
      localized in the ciliated epithelial but not in the tubular gland cells of the
      isthmus, in the ciliated epithelial cells of the red isthmus, and in the non
      ciliated epithelial cells of the shell gland. The occurrence of osteopontin in
      each of the oviduct regions, coincided with the concomitant presence of the egg
      in such region. Considering the reported inhibitory function of osteopontin in
      other mineralized systems, together with its main occurrence in the non
      mineralized parts of the eggshell and at the outermost part of the shell,
      suggests that this molecule could be part of the mechanism regulating the
      eggshell calcification.

PMID- 14572473
TI  - Side-chain conformation angles of amino acids: effect of temperature factor cut
      off.
AB  - The paper presents the analysis of the side-chain conformation angles of amino
      acids in 90% non-identical protein structures. The analysis has been carried out
      using 113,699 residues, which is higher compared to the previous studies. In the
      present study, one more quality check, namely, temperature factor cut-off, has
      been introduced in addition to resolution and R-factor cut-offs. Due to this, the
      present calculation reveals the approximate values for the minimum and the
      maximum of the three-rotameric states of chi1. In addition, the conformation
      angles chi2 and chi3 have been addressed with the improved data set. The results
      reported here could be of use in protein modeling.

PMID- 14572474
TI  - Topology representing network enables highly accurate classification of protein
      images taken by cryo electron-microscope without masking.
AB  - In single-particle analysis, a three-dimensional (3-D) structure of a protein is
      constructed using electron microscopy (EM). As these images are very noisy in
      general, the primary process of this 3-D reconstruction is the classification of
      images according to their Euler angles, the images in each classified group then
      being averaged to reduce the noise level. In our newly developed strategy of
      classification, we introduce a topology representing network (TRN) method. It is
      a modified method of a growing neural gas network (GNG). In this system, a
      network structure is automatically determined in response to the images input
      through a growing process. After learning without a masking procedure, the GNG
      creates clear averages of the inputs as unit coordinates in multi-dimensional
      space, which are then utilized for classification. In the process, connections
      are automatically created between highly related units and their positions are
      shifted where the inputs are distributed in multi-dimensional space.
      Consequently, several separated groups of connected units are formed. Although
      the interrelationship of units in this space are not easily understood, we
      succeeded in solving this problem by converting the unit positions into two
      dimensional (2-D) space, and by further optimizing the unit positions with the
      simulated annealing (SA) method. In the optimized 2-D map, visualization of the
      connections of units provided rich information about clustering. As demonstrated
      here, this method is clearly superior to both the multi-variate statistical
      analysis (MSA) and the self-organizing map (SOM) as a classification method and
      provides a first reliable classification method which can be used without masking
      for very noisy images.

PMID- 14572475
TI  - Impact of decellularization of xenogeneic tissue on extracellular matrix
      integrity for tissue engineering of heart valves.
AB  - The multidisciplinary research of tissue engineering utilizes biodegradable or
      decellularized scaffolds with autologous cell seeding. Objective of this study
      was to investigate the impact of different decellularization protocols on
      extracellular matrix integrity of xenogeneic tissue by means of multiphoton
      femtosecond laser scanning microscopy, biochemical and histological analysis.
      Pulmonary valves were dissected from porcine hearts and placed in a solution of
      trypsin-EDTA and incubated at 37 degrees C for either 5, 8, or 24 h, followed by
      a 24 h PBS washing. Native and decellularized valves were processed for
      histology, DNA, cell proliferation, matrix proteins and biomechanical testing.
      Multiphoton NIR laser microscopy has been applied for high-resolution 3D imaging
      of collagen and elastin. Distinct differences in several ECM components following
      decellularization time were observed. Total GAG contents decreased in a time
      dependent manner, with o-sulfated GAGs being more susceptible to degradation than
      n-sulfated GAGs. Efficiency of insoluble collagen extraction increased
      proportionally with decellularization time, suggesting ECM-integrity may be
      compromised with prolonged incubation. Biomechanical testing revealed a gradual
      weakening of mechanical strength with increased decellularization time. The
      enzymatic decellularization process of heart valves revealed a time-dependent
      loss of cells, ECM components and biomechanical strength. In order to avoid any
      immune response a thorough decellularization of 24 h remains mandatory.

PMID- 14572476
TI  - Structure and metal binding studies of the second copper binding domain of the
      Menkes ATPase.
AB  - Biological utilisation of copper requires that the metal, in its ionic forms, be
      meticulously transported, inserted into enzymes and regulatory proteins, and
      excess be excreted. To understand the trafficking process, it is crucial that the
      structures of the proteins involved in the varied processes be resolved. To
      investigate copper binding to a family of structurally related copper-binding
      proteins, we have characterised the second Menkes N-terminal domain (MNKr2). The
      structure, determined using 1H and 15N heteronuclear NMR, of the reduced form of
      MNKr2 has revealed two alpha-helices lying over a single beta-sheet and shows
      that the binding site, a Cys(X)2Cys pair, is located on an exposed loop. 1H-15N
      HSQC experiments demonstrate that binding of Cu(I) causes changes that are
      localised to conserved residues adjacent to the metal binding site. Residues in
      this area are important to the delivery of copper by the structurally related
      Cu(I) chaperones. Complementary site-directed mutagenesis of the adjacent
      residues has been used to probe the structural roles of conserved residues.

PMID- 14572477
TI  - Corrim-based alignment for improved speed in single-particle image processing.
AB  - The technique of single-particle electron cryomicroscopy is currently making
      possible the 3D structure determination of large macromolecular complexes at
      constantly increasing levels of resolution. Work at resolution now attainable
      requires many thousands of individual images to be processed computationally. The
      most time-consuming step of the image-processing procedure is usually the
      iterative alignment of individual particle images against a set of reference
      images derived from a preliminary 3-D structure. We have developed an improved
      multireference alignment procedure based on interpolated cross-correlation images
      (corrims) that results in an approximately 8-fold acceleration of the iterative
      alignment steps. These corrims can be used to restrict the number of image
      alignment calculations by narrowing down the set of reference images. Another
      improvement in alignment speed has been achieved by optimising the software and
      its implementation on many parallel processors. This new corrim-based refinement
      has been found to work well with two different alignment algorithms, the commonly
      used "fast alignment by separate translational/rotational searches" and
      "exhaustive alignment by polar coordinates."

PMID- 14572478
TI  - The molecular deposition of transgenically modified starch in the starch granule
      as imaged by functional microscopy.
AB  - The molecular deposition of starch extracted from normal plants and
      transgenically modified potato lines was investigated using a combination of
      light microscopy, environmental scanning electron microscopy (ESEM) and confocal
      laser scanning microscopy (CLSM). ESEM permitted the detailed (10 nm)
      topographical analysis of starch granules in their hydrated state. CLSM could
      reveal internal molar deposition patterns of starch molecules. This was achieved
      by equimolar labelling of each starch molecule using the aminofluorophore 8-amino
      1,3,6-pyrenetrisulfonic acid (APTS). Starch extracted from tubers with low
      amylose contents (suppressed granule bound starch synthase, GBSS) showed very
      little APTS fluorescence and starch granules with low molecular weight
      amylopectin and/or high amylose contents showed high fluorescence. Growth ring
      structures were sharper in granules with normal or high amylose contents. High
      amylose granules showed a relatively even distribution in fluorescence while
      normal and low amylose granules had an intense fluorescence in the hilum
      indicating a high concentration of amylose in the centre of the granule.
      Antisense of the starch phosphorylating enzyme (GWD) resulted in low molecular
      weight amylopectin and small fissures in the granules. Starch granules with
      suppressed starch branching enzyme (SBE) had severe cracks and rough surfaces.
      Relationships between starch molecular structure, nano-scale crystalline
      arrangements and topographical-morphological features were estimated and
      discussed.

PMID- 14572479
TI  - Individual cartilage aggrecan macromolecules and their constituent
      glycosaminoglycans visualized via atomic force microscopy.
AB  - Atomic force microscopy was used in ambient conditions to directly image dense
      and sparse monolayers of bovine fetal epiphyseal and mature nasal cartilage
      aggrecan macromolecules adsorbed on mica substrates. Distinct resolution of the
      non-glycosylated N-terminal region from the glycosaminoglycan (GAG) brush of
      individual aggrecan monomers was achieved, as well as nanometer-scale resolution
      of individual GAG chain conformation and spacing. Fetal aggrecan core protein
      trace length (398+/-57 nm) and end-to-end length (257+/-87 nm) were both larger
      than that of mature aggrecan (352+/-88 and 226+/-81 nm, respectively). Similarly,
      fetal aggrecan GAG chain trace length (41+/-7 nm) and end-to-end (32+/-8 nm)
      length were both larger than that of mature aggrecan GAG (32+/-5 and 26+/-7 nm,
      respectively). GAG-GAG spacing along the core protein was significantly smaller
      in fetal compared to mature aggrecan (3.2+/-0.8 and 4.4+/-1.2nm, respectively).
      Together, these differences between the two aggrecan types were likely
      responsible for the greater persistence length of the fetal aggrecan (110 nm)
      compared to mature aggrecan (82 nm) calculated using the worm-like chain model.
      Measured dimensions and polymer statistical analyses were used in conjunction
      with the results of Western analyses, chromatographic, and carbohydrate
      electrophoresis measurements to better understand the dependence of aggrecan
      structure and properties on its constituent GAG chains.

PMID- 14572480
TI  - Repetitive versus monomeric antigen presentation: direct visualization of
      antibody affinity and specificity.
AB  - The concept of presenting antigens in a repetitive array to obtain high titers of
      specific antibodies is increasingly applied by using surface-engineered viruses
      or bacterial envelopes as novel vaccines. A case for this concept was made 25
      years ago, when producing high-titer antisera against ordered arrays of gp23, the
      major capsid protein of bacteriophage T4 (Aebi et al., Proc. Natl. Acad. Sci.
      USA, 74 (1977) 5514-5518). In view of the current interest in this concept we
      thought it useful to employ this system to directly visualize the dependence of
      antibody affinity and specificity on antigen presentation. We compared antibodies
      raised against T4 polyheads, a tubular variant of the bacteriophage T4 capsid,
      which have gp23 hexamers arranged in a crystalline lattice (gp23(repetitive)),
      with those raised against the hexameric gp23 subunits (gp23(monomeric)). The
      labeling patterns of Fab-fragments prepared from these antibodies when bound to
      polyheads were determined by electron microscopy and image enhancement. Anti
      gp23(repetitive) bound in a monospecific, stoichiometric fashion to the gp23
      units constituting the polyhead surface. In contrast, anti-gp23(monomeric)
      decorated the polyhead surface randomly and with a 40-fold lower occupancy. These
      results concur with the difference in titers established by ELISA for the
      antisera against the repetitively displayed form of antigen (anti
      gp23(repetitive)) and the randomly presented antigen (gp23(monomeric)), and they
      constitute a compelling visual documentation of the concept of repetitive antigen
      presentation to elicite a serotype-like immune response.

PMID- 14572481
TI  - The global epidemiology of invasive Candida infections--is the tide turning?
AB  - Invasive candidiasis is a condition of major medical importance. Its incidence
      has increased dramatically over the last 50 years, reflecting increasingly
      interventional standards of medical care. Candida spp. are regularly reported to
      be the fourth commonest cause of bloodstream infection, and it is perceived that
      the incidence of invasive Candida spp. infections continues to increase. The
      global disease burden of invasive Candida spp. infections is difficult to
      quantify because of wide geographic variation. Data originating from the United
      States indicate that mortality from candidiasis has been falling since 1989. Data
      from several locations have shown that the dramatic increases in Candida spp.
      bloodstream infections seen during the 1980s were not sustained through the
      1990s. Some authors have reported a decreasing incidence. The contribution of non
      albicans Candida spp. to invasive infection is rising. Invasive infections with
      Candida spp. continue to represent a major economic burden, increasing both
      mortality and morbidity in an already expensive group of hospital patients. There
      remains much scope for ongoing and future research into the epidemiology and
      basic disease processes underlying these infections.

PMID- 14572482
TI  - Long-term epidemiological survey of Candida species: comparison of isolates found
      in an intensive care unit and in conventional wards.
AB  - The aim of this study was to compare the distribution of Candida species in
      patients hospitalized in an intensive care unit (ICU) and in conventional wards.
      A retrospective analysis was performed covering an 18-year period in a 700-bed
      teaching hospital. Various body sites were investigated in all patients admitted
      during the study and isolates were identified by microscopic and macroscopic
      morphology, and by commercially available kits. The susceptibility of strains to
      amphotericin B and flucytosine was assessed by the ATB-fungus system,
      itraconazole and fluconazole by Etest. No difference was observed between the
      distribution of Candida species in ICU and in conventional wards. Candida
      albicans represented about 70% of isolates and Candida glabrata was the second
      most common species involved in infection or colonization. The small number of C.
      glabrata resistant to fluconazole suggested this antifungal agent as suitable
      empirical treatment for non-immunocompromized patients in whom a fungal infection
      was suspected.

PMID- 14572483
TI  - National surveillance of methicillin-sensitive and methicillin-resistant
      Staphylococcus aureus in Austrian hospitals: 1994-1998.
AB  - In 1994, the Austrian Federal Ministry for Labour, Health and Social Affairs
      initiated a nationwide survey of the prevalence of methicillin-sensitive (MSSA)
      and methicillin-resistant Staphylococcus aureus (MRSA) in Austrian hospitals. A
      questionnaire had to be filled out by the medical directors of participating
      hospitals. During the five years of surveillance (1994-1998), a total of 9385
      MRSA and 71510 MSSA episodes of infection/colonization were reported. The rate of
      MRSA decreased from 15.8% in 1994 to 8.2% in 1998. However, the frequency per
      1000 hospital admissions increased from 0.85 to 1.29 with a maximum of 2.42 MRSA
      episodes per 1000 admissions in 1997. Overall, in 53.6% of 5020 S. aureus
      episodes, signs and symptoms of an infection were reported, of these 9.3%
      (251/2692) were due to MRSA. For large hospitals with more than 1000 beds, 20.9%
      of reported MRSA episodes were associated with infection, 54.9% of MRSA episodes
      from hospitals with 301-1000 beds, 60.1% from hospitals with 101-300 beds, and
      80.0% from small hospitals with less than 100 beds. Our data do not support the
      hypothesis of higher virulence of MRSA compared with MSSA. Indeed, in this
      survey, MSSA episodes were more frequently associated with signs and symptoms of
      infection (OR=1.35, 95% CI: 1.12-1.62, P<0.001).

PMID- 14572484
TI  - Stenotrophomonas maltophilia contamination of nebulizers used to deliver
      aerosolized therapy to inpatients with cystic fibrosis.
AB  - There is circumstantial evidence that nebulizer equipment may be a source of
      Stenotrophomonas maltophilia for patients with cystic fibrosis. Eighty-nine
      inpatient nebulizers were examined for evidence of S. maltophilia contamination
      of which nine (10%) yielded 14 strains of the bacterium. Environmental samples
      were obtained from 73 different sites on the ward, of which 17 (23%) yielded a
      further 21 strains. Positive sites included taps, sink drains, and potable water.
      Genotyping using ERIC-PCR and pulsed-field gel electrophoresis revealed that two
      pairs of patients' nebulizers were contaminated with closely related strains.
      None of the S. maltophilia isolates obtained from the ward environment shared
      genotypes with those obtained from the nebulizers. The frequency of isolation of
      S. maltophilia from potable water sources on the ward suggests that contamination
      may result from using it to clean reusable nebulizer equipment, particularly if
      this is followed by inadequate drying. Although the actual source of S.
      maltophilia contamination of hospital-use nebulizer equipment in this study
      remained elusive, these results have important infection control implications.

PMID- 14572485
TI  - Staphylococcal species in the oral cavity from patients in a regional burns unit.
AB  - The aim of this study was to perform a quantitative and qualitative analysis of
      oral carriage of staphylococci in a range of oral specimens from patients
      admitted to a regional burns unit. The study recruited 28 patients and reasons
      for admittance were: burns (46%), skin grafting (39%), lacerations (7%), scalding
      (4%) and necrotizing fasciitis (4%). No patient had smoke inhalation injuries or
      trauma to the oro-pharynx. There were five patients from whom methicillin
      sensitive S. aureus (MRSA) could be detected in oral specimens. For three
      patients only the wound and oral specimens were positive for MRSA. In one patient
      only the oral specimens were positive for MRSA. There were five patients from
      whom methicillin-sensitive S. aureus (MRSA) could be detected in the oral
      specimens. In one patient only the oral specimens were positive for MSSA.
      Staphylococci could be recovered from the dental plaque, denture and toothbrush
      specimens with a mean count of 1.1 x 10(4)cfu/mL (range 20-5.3 x 10(4)), 5.4 x
      10(3) (range 40-2.1 x 10(4)) and 264 cfu/mL (range 20-500), respectively. Both
      MSSA and MRSA could be recovered from these specimen types. In one patient only
      the toothbrush was positive for MRSA and all other oral specimens were negative.
      This study suggests that staphylococci are not infrequent colonizers of the oral
      cavity, and that this site may serve as a potential reservoir for transmission to
      other body sites.

PMID- 14572486
TI  - Economic impact of healthcare-associated rotavirus infection in a paediatric
      hospital.
AB  - The aim of this prospective study was to determine the extra-length of stay and
      the average cost for rotavirus healthcare-associated infection (HAI). Children
      admitted to the paediatric ward of the Reims University Hospital between the 1
      December 2001 and 31 March 2002, were included in a pairwise matched (1:1) case
      control study. Cases were defined as patients with rotavirus HAI. Controls were
      selected according to matching variables in a stepwise fashion. The costs
      measured in this study included all expenses sustained by the hospital.
      Information on costs was obtained from medical records and the hospital economic
      department. The attack rate and the incidence of healthcare-associated acquired
      rotavirus infection were 6.6% and 15.8 per 1000 hospital days, respectively,
      during a winter outbreak. Fifteen percent of HAI were identified after discharge.
      The average cost per case was 1930 and the mean excess length of stay was 4.9
      days. Our findings clearly demonstrate the substantial expense incurred as a
      result of HAI caused by rotavirus in children. To prevent these costly
      infections, several cost-effective measures such as standard precautions should
      be reinforced in the education of the healthcare workers.

PMID- 14572487
TI  - Susceptibility trends in bacteraemias: analyses of 7544 patient-unique
      bacteraemic episodes spanning 11 years (1990-2000).
AB  - The aim of the present study was to design more accurate tools for the selection
      of appropriate antimicrobial therapy for hospitalized patients with suspected
      sepsis. We created a large database comprising data on all patient-unique blood
      cultures obtained over an 11 year period (1 January, 1990 through 31 December,
      2000). Improved statistical tools were applied to assess the trends in in vitro
      activity of individual antibiotic agents against various bacteria over time, and
      to calculate susceptibility rates of subsets of organisms. During the 11 year
      study period, 173571 blood cultures were obtained, of which 17703 (10.2%) were
      positive, with 7544 patient-unique blood cultures (4.3%). The mean annual number
      of positive, patient-unique cultures was 686 (standard deviation=79). The 10 most
      frequently isolated organisms were: Escherichia coli (1494), Staphylococcus
      aureus (1240), Klebsiella pneumoniae (779), Enterococcus spp. (631), Pseudomonas
      aeruginosa (488), Streptococcus pneumoniae (447), Enterobacter spp. (338),
      Acinetobacter spp. (298), Proteus mirabilis (260) and Candida spp. (254). No
      significant change was detected in the annual rates (means, standard deviations)
      per 1000 admissions of these organisms: the highest was E. coli (5.5, 1), the
      lowest was Candida (1, 0.3). Forty percent of organisms (N=2943) were obtained
      from patients in the emergency department (ED), 23% (1744) in medical
      departments, 15% (1134) in paediatric units, 13% (998) on surgical wards and 9%
      (709) in intensive care units (ICUs). Trend statistical analysis revealed a
      significant decrease in susceptibility in ED Enterobacteriaceae to eight of 15
      (53%) tested antimicrobials, with a mean annual decrease of 1.6%+/-0.6%, in the
      ICU isolates, a significant decrease was detected in only five (33%) of the
      tested antimicrobials, with a mean annual decrease of 2.5%+/-1.3%. The difference
      in susceptibility between ED and ICU isolates was significant for all
      antimicrobials (P<0.001). A significant decrease in the susceptibility of E coli
      to nine of 15 drugs (60%) was detected, ranging from 0.7% to 2.7% annually. In K.
      pneumoniae a significant decrease in susceptibility of K. pneumoniae was detected
      with only two agents. Pseudomonas spp. isolates remained highly sensitive to all
      traditional anti-pseudomonal agents, without significant decay in sensitivity
      rates over time. Susceptibility of S. aureus to methicillin decreased
      significantly for several subsets of patients (P<0.001). Marked differences in
      susceptibility rates between the departments were detected. Trend statistical
      analyses, when appropriately applied to multi-year databases of microbial
      susceptibilities, may yield susceptibility tables that are significantly more
      accurate than traditional semi-annual or annual tables.

PMID- 14572488
TI  - Antimicrobial efficacy and potential application of a newly developed plasma
      based ultraviolet irradiation facility.
AB  - A low-pressure mercury vapour discharge tube generating high-intensity
      ultraviolet (UV) resonance radiation at 254 nm was designed to achieve a nearly
      simultaneous all-round UV irradiation of products. Testing this 'universal
      homogeneous ultraviolet (UHUV) irradiation facility' with suspended Bacillus
      subtilis spores, resulted in a 10(6)-fold reduction in viable count within 30 s
      applying irradiation energy of 0.3 mW/cm(2). Moreover, this irradiation dose
      reduced the number of immobilized B. subtilis spores on several material surfaces
      (wood-free paper, aluminium foil, polystyrol, polypropylene, and polyethylene
      foil) 10(2)-10(4)-fold. To evaluate potential applications of this UHUV
      irradiation technique under more realistic conditions, dental hand pieces and
      orthodontic forceps were contaminated by a blood-saliva mix containing
      Staphylococcus aureus. Under these conditions, a reduction in viable count of
      10(5)-10(6)-fold was achieved within 5-15 min, but higher irradiation energy
      levels up to 13 mW/cm(2) were necessary. Because of its construction, the shape
      of the newly developed UHUV irradiation device can be adapted to various shapes
      to achieve a fast and effective antimicrobial treatment.

PMID- 14572489
TI  - A prospective, randomized study in critically ill patients using the Oligon
      Vantex catheter.
AB  - Microbial colonization and the incidence of catheter-related bloodstream
      infections (CR-BSI) associated with Oligon Vantex silver central venous catheters
      (CVC) in critically ill patients were determined. A prospective, randomized,
      controlled 17-month trial was carried out in an intensive care unit (ICU). All
      patients requiring a triple-lumen CVC for four days or longer were enrolled.
      Patients were randomized to receive a standard polyurethane CVC or an Oligon
      Vantex silver CVC. Before removal of the catheter either due to discharge from
      the ICU or suspected infection, blood for cultures was taken via the CVC and a
      peripheral site. Skin and hub swabs and catheter-tips were also cultured. Two
      hundred and six catheters, 103 in both groups, were evaluated. In the control
      group (CG) 45/103 (44%) and in the silver group (SG) 30/103 (29%) were colonized
      or had a CR-BSI (P=0.04). The SG was less likely to be colonized than the CG when
      the catheter remained in situ for eight days or less (P=0.03) or over 15 days
      (P=0.01); a second or subsequent catheter was present in the same patient
      (P=0.002), or if the CVC was placed in the internal jugular vein (P=0.05).
      Multivariate logistic-regression showed predisposing factors for catheter
      colonization were jugular and femoral sites, second or subsequent catheter, and
      being a member of the CG. CR-BSI occurred in five cases (four in CG). Rates of CR
      BSI per 1000 catheter-days in the CG were 2.8 and in the SG, 0.8 (P<0.001). The
      Oligon Vantex silver catheter reduced the incidence of catheter-colonization and
      may decrease the risk of CR-BSI.

PMID- 14572490
TI  - Comparison of two test methods for the determination of sufficient antimicrobial
      activity of three commonly used alcohol-based hand rubs for hygienic hand
      disinfection.
AB  - In Europe, the antimicrobial efficacy of alcohol-based hand rubs is determined
      with a quantitative suspension test (prEN 12054) and a test under practical
      conditions (EN 1500). Another test method has recently been published by the
      German Society for Hygiene and Microbiology (DGHM) with four differences to the
      European system in the in vitro tests: additional qualitative suspension tests
      with product dilutions to the ineffective range; a selection of the most
      resistant Gram-negative test strains in the qualitative suspension test, which
      should be used adjacent to Pseudomonas aeruginosa in the quantitative suspension
      test; a high organic load in the quantitative suspension tests (0.3% albumin and
      0.3% sheep erythrocytes); and an aqueous control in the quantitative suspension
      test. According to DGHM, the in vitro tests should be followed by EN 1500. We
      have determined the antimicrobial efficacy of three commonly used alcohol-based
      hand rubs according to both methods. prEN 12054 was carried out without organic
      load. The qualitative suspension tests (DGHM) were carried out with P.
      aeruginosa, Escherichia coli, Proteus mirabilis, Staphylococcus aureus,
      Enterococcus hirae and Candida albicans. The quantitative suspension test (DGHM)
      was carried out with product dilutions of 75%, 50% and 25%, and a high organic
      load using the following test organisms: P. aeruginosa, P. mirabilis (one product
      only), S. aureus, E. hirae and C. albicans. All these suspension tests were
      carried out in quadruplicate with each product and exposure time. EN 1500 was
      carried out with 3 mL of each product and an application time of 30 s. All three
      products achieved the required bactericidal activity of prEN 12054 and the new
      DGHM method within 30 s, and were equally effective with the reference hand
      disinfection of EN 1500 within 30 s. In our study, the DGHM test method did not
      provide additional information for hand rubs which exhibit their bactericidal
      efficacy with 3 mL within 30 s (EN 1500).

PMID- 14572491
TI  - Validity of the four European test strains of prEN 12054 for the determination of
      comprehensive bactericidal activity of an alcohol-based hand rub.
AB  - A comprehensive bactericidal activity of an alcohol-based hand rub is essential
      for prevention of cross-transmission by the hands of healthcare workers. In
      Europe, however, only four test organisms are used to determine bactericidal
      activity according to prEN 12054. The susceptibility of the various bacterial
      species against the commonly used alcohols is thought to be similar, but so far
      this has never been studied. We therefore evaluated the bactericidal activity of
      an alcohol-based hand rub (Sterillium) within 30 s in compliance with prEN 12054
      and in a time kill test against 13 Gram-positive, 18 Gram-negative bacteria and
      14 antibiotic-resistant bacterial pathogens. Each strain was evaluated in
      quadruplicate. Counts of the four test bacteria of prEN 12054 were reduced by
      factors exceeding 10(5) within 30 s. In the time kill test, all 13 Gram-positive
      and all 18 Gram-negative bacteria were reduced more than 10(5)-fold within 30 s,
      not only against the ATCC test strains but also against corresponding clinical
      isolates. Comparable reductions were also observed against all 14 emerging
      bacterial pathogens. The four European test bacteria were found to be sufficient
      to determine a comprehensive bactericidal activity of a propanol-based hand rub.

PMID- 14572492
TI  - Management of a patient with Lassa fever to prevent transmission.

PMID- 14572493
TI  - Potential transmission of Creutzfeldt-Jakob disease after low-risk surgery.

PMID- 14572494
TI  - Bacterial colonization of stethoscopes and the effect of cleaning.

PMID- 14572495
TI  - Re: Evaluation of the bactericidal effect of five products for surgical hand
      disinfection according to prEN 12054 and prEN 12791. Marchetti MG et al. J Hosp
      Infect 2003;54:63-67.

PMID- 14572496
TI  - Discussion on the reverberatory model of short-term memory: a computational
      approach.
AB  - Up to now a number of models have been proposed to underlie memory formation in
      the central nervous system. Two of these models are the reverberatory circuit
      model and the other one the self-feedback loop model. This paper considers these
      two models regarding their ability to preserve neural activity and to hold
      information. In the self-feedback loop model, the activity level of the loop
      output is computed regarding the short lasting initial input. In the
      reverberatory circuit model, the activity levels of the proposed two-layer
      network outputs were computed regarding the short lasting initial inputs of the
      network. In the self-feedback loop model, the activity level of the loop output
      changes with each reverberation until it reaches a specific limit and then
      remains at that level. In the reverberatory circuit model, the activity levels of
      the proposed two-layer network outputs display an oscillatory behavior. These
      models can preserve the input activity, but they change its level with each
      reverberation. Information carried by a single neuron is related to its activity
      level. Therefore these models change the information during the reverberation.
      Short-term memory must hold the information for a certain period of time, so
      these models cannot be proposed to underlie short-term memory formation.

PMID- 14572497
TI  - A second Leonardo da Vinci?
AB  - We describe a young woman who suddenly began mirror writing with her right hand
      and has not reverted to normal writing for more than 6 years, although she writes
      normally with her left hand. She is ambidextrous, although she had previously
      used only her right hand for writing and drawing. Since it is much easier for her
      to use right-handed mirror writing, she uses her left hand only for writing meant
      to be read by others and her right hand for all other writing. Her hobbies are
      sculpture and painting, and her chief complaint is migraine accompanied by
      sensory and perceptive disturbances.

PMID- 14572498
TI  - Do separate processes identify objects as exemplars versus members of basic-level
      categories? Evidence from hemispheric specialization.
AB  - When an object is identified as a specific exemplar, is it analyzed differently
      than when it is identified at the basic level? On the basis of a previous theory,
      we predicted that the left hemisphere (LH) is specialized for classifying objects
      at the basic level and the right hemisphere (RH) is specialized for classifying
      objects as specific exemplars. To test this prediction, participants were asked
      to view lateralized pictures of animals, artifacts, and faces of famous people;
      immediately after each picture was presented, a label was read aloud by the
      computer, and the participants decided whether the label was correct for that
      picture. A label could name the object at either the basic level (e.g., bird) or
      as an exemplar (e.g., robin). As predicted, we found that basic-level labels were
      matched faster when pictures were presented in the right visual field (and hence
      encoded initially in the LH), whereas exemplar labels were matched faster when
      pictures were presented in the left visual field (and hence encoded initially in
      the RH).

PMID- 14572499
TI  - Brain potentials elicited by matching global and occluded 3-dimensional contours.
AB  - Subjects were instructed to match 3-dimensional forms while event-related
      potentials (ERPs) were recorded to explore the relationship between visual
      completion and conflict processing. Sequentially presented paired stimuli (S1 and
      S2) were identical in condition I, while in condition II the images were of the
      same contour, but S2 contained an invisible portion, and in condition III S1 and
      S2 were of different contours. Subjects indicated if stimuli were physically
      identical or contour similar in two separate sessions. Following the onset of S2,
      ERP components P100, N150, and LPC were recorded in all conditions. N150 was
      enhanced in condition II in both sessions, and N270 was elicited in conditions II
      and III. N150 is related to visual completion, while N270 is related to the
      evaluation of information discrepancy, belonging to independent systems.

PMID- 14572500
TI  - Hemispheric asymmetries for selective attention apparent only with increased task
      demands in healthy participants.
AB  - This study examined the possibility that lack of behavioral evidence indicating
      hemispheric specialization for selective attention in healthy individuals is due
      to the use of tasks that are not sufficiently demanding to require selective
      attention. In a group of 43 participants (ages 17-23), we compared selective
      attention on a cued-response time task when the target was presented alone and
      when a distractor was simultaneously presented. The costs of invalid cueing were
      minimal when the right hemisphere (RH) processed the target relative to when the
      left hemisphere (LH) processed the target, but only for the high load condition.
      These results are interpreted as RH specialization in light of evidence
      suggesting that the RH can direct attention to a larger portion of the visual
      field.

PMID- 14572502
TI  - Alcoholism risk and the P300 event-related brain potential: modality, task, and
      gender effects.
AB  - The P300 event related potential (ERP) was elicited from young adults at low-
      (LR) and high-risk (HR) for alcoholism (n = 24/risk group), with equal numbers of
      male and female subjects employed. The effects of stimulus modality, task
      difficulty, and gender were assessed with analogous auditory and visual paradigms
      (tone location/head rotation and tone matching/shape matching). Although task
      performance was generally comparable across risk groups, LR subjects produced
      smaller P300 amplitudes than HR subjects for the visual matching tasks. No
      consistent risk group P300 latency effects were obtained. Gender, task
      difficulty, and scalp topography differentially modulated the risk group outcomes
      across paradigms. These findings suggest that P300 amplitude reflects risk-for
      alcoholism in male and female young adults, but the specific task conditions and
      electrode location affect the strength of risk group differences.

PMID- 14572503
TI  - The interactive effects of alcohol and temazepam on P300 and reaction time.
AB  - The present research investigated the separate and interactive effects of the
      minor tranquilizer, temazepam, and a low dose of alcohol on the amplitude and
      latency of P300 and on reaction time. Twenty-four participants completed four
      drug treatments in a repeated measures design. The four drug treatments,
      organised as a fully repeated 2 x 2 design, included a placebo condition, an
      alcohol only condition, a temazepam only condition, and an alcohol and temazepam
      combined condition. Event-related potentials were recorded from midline sites Fz,
      Cz, and Pz within an oddball paradigm. The results indicated that temazepam, with
      or without the presence of alcohol, reduced P300 amplitude. Alcohol, on the other
      hand, with or without the presence of temazepam, affected processing speed and
      stimulus evaluation as indexed by reaction time and P300 latency. At the low dose
      levels used in this experiment alcohol and temazepam appear not to interact,
      which suggests that they affect different aspects of processing in the central
      nervous system.

PMID- 14572504
TI  - Effects of tobacco smoking on electroencephalographic, auditory evoked and event
      related potentials.
AB  - After overnight abstinence, tobacco smokers smoked an average nicotine yield
      cigarette and nonsmokers sham smoked an unlit placebo cigarette. EEG alpha(1),
      delta, and theta frequency amplitudes decreased, whereas alpha(2) and beta
      frequency amplitude increased. Short, middle (EP) and long latency ERP were also
      studied in nonsmokers and smokers just after smoking, and after overnight
      abstinence from tobacco. Short latency potentials were unaffected by tobacco
      smoking or abstinence. Middle and long-latency potentials were reduced during
      abstinence and enhanced immediately after tobacco smoking. These findings
      indicate that compared to nonsmokers smokers have a higher arousal level after
      smoking than when partially abstinent. Evidence for both normalization from
      tobacco abstinence as well as stimulation was obtained.

PMID- 14572505
TI  - EEG effects of conventional and denicotinized cigarettes in a spaced smoking
      paradigm.
AB  - Although there is a documented association between plasma nicotine levels and
      smoking behavior, recent studies indicate that denicotinized cigarettes reduced
      craving and symptoms of tobacco withdrawal. Denicotinized cigarettes (that
      deliver tar but insignificant amounts of nicotine) and conventional cigarettes
      were compared in a within-subject spaced smoking study. In six sessions, subjects
      (n=10) smoked denicotinized cigarettes or conventional cigarettes every 30, 60 or
      240 min (8, 4 or 1 cigarette(s)). EEG effects of the last cigarette of each
      session were deduced by comparisons with EEG recordings collected before smoking.
      Conventional cigarettes increased spectral edge EEG frequency, decreased theta
      power and increased beta1 power. Denicotinized cigarettes decreased spectral
      frequency. The EEG effects of both cigarettes depended upon the recentness of
      smoking. The results indicate that nicotine delivery, recentness and the process
      of smoking importantly influence the EEG; other, non-nicotine components of
      tobacco smoke may also exert EEG effects.

PMID- 14572506
TI  - Caffeine, fatigue, and cognition.
AB  - Effects of caffeine and fatigue are discussed with special attention to adenosine
      dopamine interactions. Effects of caffeine on human cognition are diverse.
      Behavioural measurements indicate a general improvement in the efficiency of
      information processing after caffeine, while the EEG data support the general
      belief that caffeine acts as a stimulant. Studies using ERP measures indicate
      that caffeine has an effect on attention, which is independent of specific
      stimulus characteristics. Behavioural effects on response related processes
      turned out to be mainly related to more peripheral motor processes. Recent
      insights in adenosine and dopamine physiology and functionality and their
      relationships with fatigue point to a possible modulation by caffeine of
      mechanisms involved in the regulation of behavioural energy expenditure.

PMID- 14572507
TI  - Redescription of Hammondia hammondi and its differentiation from Toxoplasma
      gondii.
AB  - Hammondia hammondi is a protozoan parasite that, until 1975, was misidentified as
      Toxoplasma gondii. Recently, the validity of H. hammondi has been questioned. In
      this article, the authors redescribe the parasite and its life cycle, provide
      accession numbers to its specimens deposited in a museum, and distinguish it
      structurally and biologically from T. gondii. Hammondia hammondi was found to be
      structurally, biologically, and molecularly different from T. gondii.

PMID- 14572508
TI  - Expression profiles of peroxiredoxin proteins of the rodent malaria parasite
      Plasmodium yoelii.
AB  - Patterns of expression of the 2-Cys and 1-Cys peroxiredoxin (Prx) proteins of the
      rodent malaria parasite Plasmodium yoelii during its life cycle were observed by
      immunofluorescent antibody staining and confocal laser scanning microscopy. 2-Cys
      Prx was expressed in the parasite cytoplasm throughout the life cycle, and the
      thioredoxin (Trx)-peroxidase activity of 2-Cys Prx revealed with the recombinant
      protein suggested that the Prx is constitutively expressed and, thus, likely
      plays a housekeeping role in the parasite's intracellular redox control. In
      contrast, 1-Cys Prx showed stage-specific expression in blood-stage parasites.
      The limited expression of 1-Cys Prx in the trophozoite cytoplasm suggests that 1
      Cys Prx may be involved in haemoglobin metabolism by the parasite, which
      generates a prooxidative haem iron and increases intracellular oxidative stress.
      The antioxidant activity of 1-Cys Prx was tested for its ability to protect yeast
      enolase against inactivation of the mixed-function oxidation system. Differential
      expression of the two Prx proteins during the erythrocytic and insect stages
      suggests the importance of these proteins in protecting parasites against
      oxidative stress, which is generated by the parasite's metabolism and also from
      the environment.

PMID- 14572509
TI  - Experimental Trichinella infection in seals.
AB  - The susceptibility of seals to infection with Trichinella nativa and the cold
      tolerant characteristics of muscle larvae in seal meat were evaluated. Two grey
      seals, Halichoerus grypus, were inoculated with 5000 (100 larvae/kg) T. nativa
      larvae and two grey seals with 50000 (1000 larvae/kg). One seal from each dose
      group and two control seals were killed at 5 and 10 weeks post-inoculation
      (p.i.). At 5 weeks p.i., infection was established in both low and high dose
      seals with mean larval densities of 68 and 472 larvae per gram (lpg),
      respectively, using eight different muscles for analyses. At 10 weeks p.i., mean
      larval densities were 531 and 2649 lpg, respectively, suggesting an extended
      persistence of intestinal worms. In seals with high larval density infections,
      the distribution of larvae in various muscles was uniform, but in one seal with a
      low larval density infection, predilection sites of larvae included muscle groups
      with a relative high blood flow, i.e. diaphragm, intercostal and rear flipper
      muscles. Trichinella-specific antibody levels, as measured by ELISA, increased
      during the 10 week experimental period. Infected seal muscle was stored at 5, -5
      and -18 degrees C for 1, 4 and 8 weeks. Muscle larvae released from stored seal
      muscle by artificial digestion were inoculated into mice to assess viability and
      infectivity. Larvae from seal muscle 10 weeks p.i. tolerated -18 degrees C for 8
      weeks but larvae from seal muscle 5 weeks p.i. tolerated only 1 week at -18
      degrees C, supporting the hypothesis that freeze tolerance increases with the age
      of the host-parasite tissue complex. The expressed susceptibility to infection,
      extended production of larvae, antibody response and freeze tolerance of T.
      nativa in seals are new findings from the first experimental Trichinella
      infection in any marine mammal and suggest that pinnipeds (phocids, otariiids or
      walrus) may acquire Trichinella infection by scavenging even small amounts of
      infected tissue left by hunters or predators.

PMID- 14572510
TI  - Mitochondrial DNA variation of Gyrodactylus spp (Monogenea, Gyrodactylidae)
      populations infecting Atlantic salmon, grayling, and rainbow trout in Norway and
      Sweden.
AB  - Approximately 800 bp of the mitochondrial cytochrome oxidase I (COI) gene were
      sequenced from 76 Gyrodactylus specimens of 32 salmonid host populations, i.e.
      from Salmo salar, Thymallus thymallus, and Oncorhynchus mykiss in Norway, Sweden
      and Latvia. The COI sequences indicated a substantial intraspecific
      differentiation of Gyrodactylus salaris and Gyrodactylus thymalli. In total, 12
      haplotypes were identified which group into five well supported clades, three
      clades with parasites from Atlantic salmon and two clades with parasites from
      grayling. The basal nodes linking the five clades together are only weakly
      supported. Thus, there is no support for the monophyly of all G. salaris
      haplotypes and the monophyly of all G. thymalli haplotypes. The lack of monophyly
      of the mitochondrial haplotypes of G. salaris and G. thymalli may indicate that
      G. salaris and G. thymalli represent (i). two polytypic species or (ii). one
      polytypic species, or (iii). refer to a complex of more than two sibling species.
      The mtDNA data indicate multiple introductions of G. salaris and G. thymalli into
      Norway. A minimum of three independent introductions of G. salaris and two
      independent introductions of G. thymalli are supported. This is congruent with
      earlier hypotheses on the introduction of G. salaris and G. thymalli into Norway.

PMID- 14572511
TI  - Population genetic structure of Taenia solium from Madagascar and Mexico:
      implications for clinical profile diversity and immunological technology.
AB  - Taenia solium is a cestode parasitic of humans and pigs that strongly impacts on
      public health in developing countries. Its larvae (cysticercus) lodge in the
      brain, causing neurocysticercosis, and in other tissues, like skeletal muscle and
      subcutaneous space, causing extraneuronal cysticercosis. Prevalences of these two
      clinical manifestations vary greatly among continents. Also, neurocysticercosis
      may be clinically heterogeneous, ranging from asymptomatic forms to severely
      incapacitating and even fatal presentation. Further, vaccine design and diagnosis
      technology have met with difficulties in sensitivity, specificity and
      reproducibility. Parasite diversity underlying clinical heterogeneity and
      technological difficulties is little explored. Here, T. solium genetic population
      structure and diversity was studied by way of random amplified polymorphic DNA in
      individual cysticerci collected from pigs in Madagascar and two regions in
      Mexico. The amplification profiles of T. solium were also compared with those of
      the murine cysticercus Taenia crassiceps (ORF strain). We show significant
      genetic differentiation between Madagascar and Mexico and between regions in
      Mexico, but less so between cysticerci from different localities in Mexico and
      none between cysticerci from different tissues from the same pig. We also found
      restricted genetic variability within populations and gene flow was estimated to
      be low between populations. Thus, genetic differentiation of T. solium suggests
      that different evolutionary paths have been taken and provides support for its
      involvement in the differential tissue distribution of cysticerci and varying
      degrees of severity of the disease. It may also explain difficulties in the
      development of vaccines and tools for immunodiagnosis.

PMID- 14572512
TI  - B cells and antibody response in calves primary-infected or re-infected with
      Cooperia oncophora: influence of priming dose and host responder types.
AB  - We investigated whether the generation of protective memory humoral immunity in
      Cooperia oncophora infected calves occurs in a dose-dependent way and whether it
      depends on the animal responder types. To this end, serum and mucus antibody
      responses were measured in animals primary-infected with 30000 or 100000 L3,
      treated with anthelmintics and subsequently challenged with 100000 L3. A detailed
      phenotypic and functional analysis of B cells was done in animals infected once
      or twice with 100,000 L3. Based on the similarity in parasitological variables of
      animals primed with 30000 or 100000 L3, we concluded that with these doses
      priming conferred protection in a dose-independent way. Upon challenge
      significant increases in Cooperia-specific serum and mucus IgG1 and IgA and total
      serum IgE titres were induced in primed animals in a dose-independent way. In
      contrast, intermediate and low responders differed in the onset of the production
      of Cooperia-specific serum IgG1. Furthermore, not only the onset but also the
      level of total serum IgE significantly differed between intermediate and low
      responders. Phenotypic and functional analysis of B lymphocytes revealed that
      (i). priming induced the generation of memory B cells which upon challenge
      readily differentiated into antibody secreting cells; (ii). sensitised B cells
      were more efficiently recruited to the intestinal effector sites; (iii). based on
      the expression of CD62L and CD86 two distinct B cell subpopulation could be
      differentiated. CD62L(+)CD86(-) B cells that were likely lymphocytes not yet
      activated and with an enhanced recirculation capacity, and CD62L(-)CD86(+) B
      cells that were activated B cells with a reduced recirculation ability; and
      finally (iv). the increased expression of CD86 and subsequent correlations with
      parameters of the T helper 2 immune response induced by C. oncophora, suggested
      that CD86- interactions are involved in the generation of protective immunity
      against Cooperia.

PMID- 14572513
TI  - T-cell mediated immune responses in calves primary-infected or re-infected with
      Cooperia oncophora: similar effector cells but different timing.
AB  - Cooperia oncophora is the most prevalent intestinal nematode of cattle occurring
      in Western Europe. Primary infection with 100000 third stage infective larvae
      (L3) induces acquired immunity in a high proportion of the animals but there is
      little information on immunity against re-infection. In the current experiment,
      the contribution of the T-cell mediated immunity in protection against re
      infection with C. oncophora was investigated in detail. Priming elicited long
      lasting protective immunity that was evidenced by a significantly decreased worm
      burden and egg excretion in primed animals compared to challenge control animals.
      Lymphocyte proliferation tests with excretory/secretory products (ESP) of C.
      oncophora and with three distinct ESP fractions indicated an enhanced reactivity
      in primed animals and suggested that by fractionating of ESP we selected for
      proteins involved in protective immunity against re-infection with C. oncophora.
      Phenotypic analysis of T cell subsets at diverse anatomical locations revealed
      that the enhanced reactivity of lymphocytes from peripheral blood and lymph nodes
      of the infected animals coincided with a significantly increased frequency of
      CD4(+) cells at these locations but a deceased frequency of CD4(+) cells in the
      lamina propria. These findings were independent of the immune status of the
      animals but more pronounced in the primed animals than in the challenge control
      animals. In addition we demonstrated that primary and secondary infections with
      C. oncophora were associated with two waves of eosinophils and that the kinetics
      of this cell population differed as a result of priming. Based on the observed
      correlations we propose that the early increase of eosinophils is T cell
      independent and merely a consequence of inflammation in the parasitised gut. In
      contrast, the second wave of eosinophils depends upon CD4(+) cells and
      correlations with parasitological parameters at this time point support a role of
      eosinophils as effector cells against adult stages of C. oncophora.

PMID- 14572514
TI  - Expression of mRNA for interleukin-1beta, interleukin-6, tumor necrosis factor
      alpha and macrophage migration inhibitory factor in HPA-axis tissues in
      Schistosoma mansoni-infected baboons (Papio cynocephalus).
AB  - Cytokines may regulate the function of the hypothalamic-pituitary-adrenal axis
      during schistosomiasis. This possibility was investigated in baboons
      experimentally infected with Schistosoma mansoni. Serum levels of corticotrophin
      releasing hormone, adrenocorticotrophin, cortisol and dehydroepiandrosterone were
      confirmed to be decreased in infected baboons as previously shown. To explore if
      this effect is associated with specific expression of cytokines with endocrine
      activity, and are also associated with the pathology of the disease, Northern
      blots for interleukin-1beta, interleukin-6, tumor necrosis factor-alpha and
      macrophage migration inhibitory factor in hypothalamic-pituitary-adrenal axis
      tissues were performed. Infection induced interleukin-1beta gene expression in
      the hypothalamus, while interleukin-6 and migration inhibitory factor mRNAs were
      induced only in the pituitary and adrenal glands. Tumor necrosis factor-alpha
      gene expression was induced in the hypothalamus and the pituitary gland.
      Histopathological analysis of the hypothalamic-pituitary-adrenal axis tissues in
      infected and control baboons revealed no morphological differences between them.
      These results suggest that specific cytokines expressed in hypothalamic-pituitary
      adrenal axis tissues could regulate hormone secretion during schistosomiasis.

PMID- 14572515
TI  - Characterisation of Toxoplasma gondii engineered to express mouse interferon
      gamma.
AB  - Recent studies have shown the feasibility of using Toxoplasma gondii as an
      expression system for heterologous protein. For better understanding of the
      mechanism of interferon-gamma (IFN-gamma) dependent immunity to T. gondii, the
      parasites were stably transfected with IFN-gamma gene, under control of the GRA1
      promoter. Immunofluorescence analyses showed that recombinant mouse IFN-gamma
      localised to discrete punctuate structures consistent with dense granules and
      secreted into the vacuolar space. The production of IFN-gamma was detectable in
      both extracellular parasites and the parasite-infected cells. Growth of the
      recombinant parasites was inhibited in the mouse macrophage cell line (J774A.1
      cells), but not in monkey kidney adherent fibroblasts (Vero cells), demonstrating
      the species-specificity of IFN-gamma. Addition of anti-mouse IFN-gamma antibody
      resulted in growth recovery of the recombinant parasites, suggesting that IFN
      gamma, secreted from the parasitised host cells across the parasitophorous
      vacuole membrane, acted in a paracrine manner. Reverse transcription (RT)-PCR
      analysis revealed significant expression of inducible nitric oxide synthase mRNA
      and high levels of nitric oxide production in recombinant parasite-infected
      J774A.1 cells. A competitive inhibitor of the L-arginine-dependent effector
      pathway, N(G)-monomethyl-L-arginine, inhibited the reduction of recombinant
      parasite growth in J774A.1 cells. Taken together, our data suggest that the T.
      gondii expression system may provide a new tool for cytokine gene expression and
      that parasites engineered to express a cytokine gene may be rationally designed
      for use in studies on immune responses to T. gondii.

PMID- 14572517
TI  - Application of a multi-faceted approach for the assessment of treatment response
      in falciparum malaria: a study from Malaysian Borneo.
AB  - Thirty-two patients reporting to the Lundu District Hospital, Sarawak, Malaysian
      Borneo, with uncomplicated falciparum malaria were recruited into a multifaceted
      study to assess treatment response. Following combined chloroquine and
      sulphadoxine/pyrimethamine treatment the patients were followed for 28 days
      according to the World Health Organisation in vivo drug response protocol. The in
      vivo study revealed that 13 (41%) of the patients had a sensitive response to
      treatment, five (16%) cleared asexual stage parasites but had persistent
      gametocytes, 11 (34%) had RI type resistance and three (9%) had RII type
      resistance requiring quinine intervention before day 7 for parasite clearance.
      Although clinically insignificant, patients with persistent gametocytes,
      surviving chloroquine and sulphadoxine/pyrimethamine treatment during maturation,
      were placed in the reduced response to treatment group for analysis. Allelic
      typing detected 100% prevalence of the pfcrt K76T marker associated with
      chloroquine resistance and 78% prevalence of the pfdhfr NRNL haplotype associated
      with sulphadoxine/pyrimethamine treatment failure. High serum chloroquine levels
      and pfdhfr haplotypes with <or=2 point mutations were independently associated
      with a sensitive response to treatment. However four patients in the sensitive
      response group had both low serum chloroquine levels and the pfdhfr NRNL
      haplotype. A degree of immunity, consistent with malaria endemicity, may account
      for the apparently paradoxical presence of markers of drug resistance in the
      sensitive group.

PMID- 14572516
TI  - Structure and developmental expression of Strongyloides stercoralis fktf-1, a
      proposed ortholog of daf-16 in Caenorhabditis elegans.
AB  - A forkhead transcription factor gene, fktf-1, which we propose to be orthologous
      to the Caenorhabditis elegans dauer-regulatory gene daf-16 has been discovered in
      the parasitic nematode Strongyloides stercoralis. Genomic and cDNA sequences from
      both species predict alternately spliced a and b message isoforms. In contrast to
      C. elegans, where two a isoforms, daf-16a1 and daf-16a2, are found, a single fktf
      1a isoform is found in S. stercoralis. Five of the 10 introns found in the C.
      elegans gene are found in the proposed S. stercoralis ortholog. Functional motifs
      common to DAF-16 and several mammalian forkhead transcription factors are
      conserved in FKTF-1. These include the forkhead DNA binding domain, four
      Akt/protein kinase B phosphorylation sites and a C-terminal domain that may
      associate with factors such as the steroid receptor coactivator and other factors
      necessary for transcriptional regulation. An N-terminal serine-rich domain found
      in DAF-16A is greatly expanded in FKTF-1A. This domain is missing in DAF-16B,
      FKTF-1B and all mammalian orthologs. FKTF-1 shows the closest phylogenetic
      relationship to DAF-16 among all known mammalian and nematode forkhead
      transcription factors. Like its proposed Caenorhabditis ortholog, the fktf-1
      message is expressed at all stages of the life cycle examined thus far. Discovery
      of fktf-1 indicates the presence of an insulin-like signalling pathway in S.
      stercoralis similar to that known to regulate dauer development in C. elegans.
      This pathway is a likely candidate to control infective larval arrest and
      reactivation as well as regulation of the switch between parasitic and free
      living development in the parasite.

PMID- 14572518
TI  - Partial characterisation of carbohydrate-rich Echinococcus granulosus
      coproantigens.
AB  - Coproantigen ELISA based tests for diagnosis of canine echinococcosis provide
      high specificity and sensitivity. However, the antigenic molecules present in
      faeces from infected dogs have not yet been characterised. While initial attempts
      to determine the molecular weights of Echinococcus granulosus coproantigens by
      SDS-PAGE and Western blotting with coproantigen reactive capture antibodies were
      equivocal, they suggested presence of a significant carbohydrate component.
      Periodate treatment of coproantigen positive faecal supernatants resulted in a
      significant reduction (53%) in ELISA activity, suggesting that carbohydrates are
      involved in the antigenic structure of E. granulosus coproantigens. Protease
      treatment of antigenic molecules resulted in an 11% reduction in absorbance in
      ELISA, indicating that protein components were also present which affected by
      enzyme activity. Lectin-binding ELISA assays indicated strong affinity of E.
      granulosus coproantigens to concanavalin agglutinin and Lens culinaris
      agglutinin, and moderate binding to wheat-germ agglutinin and peanut agglutinin.
      No binding was detectable to Ulex europaensis agglutinin-I, Bandeiraea
      simplicifolia or Dolichos biflorus agglutinin. These data indicate that E.
      granulosus coproantigens from infected dog faeces possibly contained alpha-D
      mannose and/or alpha-D-glucose, beta-galactose and N-acetyl-beta-glucosamine
      residues. To verify the role of carbohydrate moieties in coproantigens, faecal
      samples were treated with exoglycosidase and tested in the coproantigen ELISA.
      Treatment with beta-galactosidase or N-acetyl-beta-glucosamine reduced ELISA
      activity by 44 and 30%, respectively. Incubation with a panel of other specific
      exoglycosidases including alpha-galactosidase as well as alpha-L-fucosidase,
      alpha-mannosidase, beta-mannosidase, alpha-glucosidase, beta-glucosidase, beta-
      fructosidase, or neuraminidase, did not alter coproantigen detection in ELISA.
      The results indicate that coproantigens present in faeces from E. granulosus
      naturally infected dogs were highly glycosylated and contain beta- galactose and
      N-acetyl-beta-glucosamine. The putative relationship of antigenic molecules with
      the tapeworm glycocalyx is discussed.

PMID- 14572519
TI  - Neural correlates of thought suppression.
AB  - The present report used functional magnetic resonance imaging (fMRI) to examine
      the neural correlates of thought suppression. Subjects were imaged while
      alternately (i) attempting to suppress a particular thought, (ii) attempting to
      suppress all thoughts, or (iii) thinking freely about any thought. Suppression of
      a particular thought, when compared to the free-thought control condition,
      revealed greater activation in the anterior cingulate. When the task of
      suppressing all conscious thoughts was compared to free-thought, a more
      distributed network of brain regions, including the anterior cingulate and the
      insula, was activated. These findings are consistent with previous research on
      cognitive control and may provide potential insights into psychological disorders
      involving recurring, intrusive thoughts.

PMID- 14572520
TI  - Activation of Broca's area during the production of spoken and signed language: a
      combined cytoarchitectonic mapping and PET analysis.
AB  - Broca's area in the inferior frontal gyrus consists of two cytoarchitectonically
      defined regions-Brodmann areas (BA) 44 and 45. Combining probabilistic maps of
      these two areas with functional neuroimaging data obtained using PET, it is shown
      that BA45, not BA44, is activated by both speech and signing during the
      production of language narratives in bilingual subjects fluent from early
      childhood in both American Sign Language (ASL) and English when the generation of
      complex movements and sounds is taken into account. It is BA44, not BA45, that is
      activated by the generation of complex articulatory movements of oral/laryngeal
      or limb musculature. The same patterns of activation are found for oral language
      production in a group of English speaking monolingual subjects. These findings
      implicate BA45 as the part of Broca's area that is fundamental to the modality
      independent aspects of language generation.

PMID- 14572521
TI  - Effects of repetitive transcranial magnetic stimulation on memory subtypes: a
      controlled study.
AB  - Repetitive transcranial magnetic stimulation (rTMS) of human cortex may disrupt
      or facilitate cortical activity. The aim of the present study was to investigate
      the consequences of rTMS applied over different cortical areas during various
      memory tasks, measuring immediate, working and episodic verbal memory. The study
      was performed in 16 right-handed healthy men. A double-blind, cross-over, within
      subject repeated measures design was used. There were five rTMS conditions:
      baseline without stimulation, high frequency (HF) rTMS over right and left
      dorsolateral prefrontal cortex (DLPFC) and over right cerebellum, and low
      frequency (LF) parameters over left DLPFC. Digits forwards and backwards and
      letter-number sequencing of the Wechsler Adults Intelligence Scale (WAIS) were
      used to assess immediate and working verbal memory, and logical memory of the
      Rivermead Behavioural Memory Test was used to assess episodic memory encoding. An
      analysis of variance (ANOVA) for repeated measures in the scores of each memory
      task according to rTMS conditions was used. Significantly lower scores in the
      number of memory units of the episodic memory task were observed when rTMS high
      frequency parameters were applied over left DLPFC (P=0.009). No significant
      differences were found in the other memory subtype tasks analysed during the
      different rTMS conditions. These findings provide evidence for the significant
      role of the left DLPFC in episodic verbal memory processes.

PMID- 14572522
TI  - Evidence for interacting cortical control of vestibular function and spatial
      representation in man.
AB  - The objective of this research was to determine the possible relation between
      deficits in spatial representation capability and vestibular function following
      cortical lesions. We thus investigated vestibulo-ocular behaviour in a group of
      14 patients with unilateral cortical damage involving the occipito-temporo
      parietal junction. Patients were divided in three sub-groups: (1) Group R+: five
      patients with right sided cortical lesions associated with a left hemi-neglect,
      (2) Group R-: four patients with right sided cortical lesions with no hemi
      neglect and (3) Group L: five patients with left-sided cortical lesions. The
      patient groups were compared to a group of eight healthy age-matched subjects.
      The vestibulo-ocular reflex (VOR) was tested in complete darkness by rotating the
      subject around the vertical axis by sinusoidal rotation at different frequencies,
      and by steps of acceleration or deceleration. The nystagmus slow phase velocity
      was measured and plotted as a function of the head velocity and the VOR
      parameters including gain, bias, time constant and phase were calculated. The
      cortical lesions induced a significant VOR asymmetry in terms of: a directional
      preponderance of the VOR gain to the contralesion side, only during sinusoidal
      rotation, and, in contrast, a VOR bias and a directional preponderance of the VOR
      time constant and of the nystagmus frequency to the side of the cortical lesion.
      These latter VOR deficits were the most significant in the R+ group, i.e. in
      right cortical lesions with hemi-neglect syndrome. These results demonstrate in
      man, the existence of a cortical influence on vestibular function related to the
      mechanisms of spatial representation.

PMID- 14572523
TI  - The irrelevant speech effect: a PET study.
AB  - Positron emission tomography (PET) was performed in normal volunteers during a
      serial recall task under the influence of irrelevant speech comprising both
      single item repetition and multi-item sequences. An interaction approach was used
      to identify brain areas specifically related to the irrelevant speech effect. We
      interpreted activations as compensatory recruitment of complementary working
      memory processing, and decreased activity in terms of suppression of task
      relevant areas invoked by the irrelevant speech. The interaction between the
      distractors and working memory revealed a significant effect in the left, and to
      a lesser extent in the right, superior temporal region, indicating that initial
      phonological processing was relatively suppressed. Additional areas of decreased
      activity were observed in an a priori defined cortical network related to verbal
      working memory, incorporating the bilateral superior temporal and inferior/middle
      frontal cortices extending into Broca's area on the left. We also observed a weak
      activation in the left inferior parietal cortex, a region suggested to reflect
      the phonological store, the subcomponent where the interference is assumed to
      take place. The results suggest that the irrelevant speech effect is correlated
      with and thus tentatively may be explained in terms of a suppression of
      components of the verbal working memory network as outlined. The results can be
      interpreted in terms of inhibitory top-down attentional mechanisms attenuating
      the influence of the irrelevant speech, although additional studies are clearly
      necessary to more fully characterize the nature of this phenomenon and its
      theoretical implications for existing short-term memory models.

PMID- 14572524
TI  - Independent digit movements and precision grip patterns in 1-5-month-old human
      infants: hand-babbling, including vacuous then self-directed hand and digit
      movements, precedes targeted reaching.
AB  - Previous work has described human reflexive grasp patterns in early infancy and
      visually guided reaching and grasping in late infancy. There has been no
      examination of hand movements in the intervening period. This was the purpose of
      the present study. We video recorded the spontaneous hand and digit movements
      made by alert infants over their first 5 months of age. Over this period,
      spontaneous hand and digit movements developed from fists to almost continuous,
      vacuous movements and then to self-directed grasping movements. Amongst the many
      hand and digit movements observed, four grasping patterns emerged during this
      period: fists, pre-precision grips associated with numerous digit postures,
      precision grips including the pincer grasp, and self-directed grasps. The finding
      that a wide range of independent digit movements and grasp patterns are displayed
      spontaneously by infants within their first 5 months of age is discussed in
      relation to the development of the motor system, including the suggestion that
      direct connections of the pyramidal tract are functional relatively early in
      infancy. It is also suggested that hand babbling, consisting of first vacuous and
      then self-directed movements, is preparatory to targeted reaching.

PMID- 14572525
TI  - Dissociating medial temporal and basal ganglia memory systems with a latent
      learning task.
AB  - The medial temporal (MT) lobes and basal ganglia have both been implicated as
      brain substrates of associative learning. Here, we show a dissociation between
      medial temporal and basal ganglia damage using a latent learning task, in which
      prior exposure to cues, uncorrelated with each other, slows subsequent learning
      of an association between them. Consistent with prior work, we found a robust
      exposure effect in healthy controls, with exposed controls learning more slowly
      than non-exposed controls. This effect was abolished in medial temporal amnesia:
      both exposed and non-exposed amnesic patients learned at the same speed. A group
      of patients with basal ganglia damage due to Parkinson's disease showed a
      reversal of the effect: exposed subjects learned faster than non-exposed
      subjects. Our findings point to distinct and dissociable contributions of medial
      temporal lobe and basal ganglia structures to learning and memory.

PMID- 14572526
TI  - Neuroanatomical correlates of selected executive functions in middle-aged and
      older adults: a prospective MRI study.
AB  - Neuroanatomical substrates of age-related differences in working memory and
      perseverative behavior were examined in a sample of healthy adults (50-81 years
      old). The participants, who were screened for history of neurological,
      psychiatric, and medical conditions known to be linked to poor cognitive
      performance, underwent magnetic resonance imaging (MRI) and were administered
      tests of working memory and perseveration. Regional brain volumes and the volume
      of white matter hyperintensities (WMH) were measured on magnetic resonance
      images. The analyses indicate that the volume of the prefrontal cortex (PFC) and
      the volume of white matter hyperintensities in the prefrontal region are
      independently associated with age-related increases in perseverative errors on
      the Wisconsin Card Sorting Test (WCST). When participants taking antihypertensive
      medication were excluded from the analysis, both the volume of the prefrontal
      cortex and the frontal white matter hyperintensities (FWMH) still predicted
      increases in perseveration. Neither reduced volume of the prefrontal cortex nor
      the FWMH volume was linked to age-associated declines in working memory. The
      volumes of the fusiform gyrus (FG) and the temporal white matter hyperintensities
      (TWMH) were unrelated to cognitive performance.

PMID- 14572527
TI  - Approximate quantities and exact number words: dissociable systems.
AB  - Numerical abilities are thought to rest on the integration of two distinct
      systems, a verbal system of number words and a non-symbolic representation of
      approximate quantities. This view has lead to the classification of acalculias
      into two broad categories depending on whether the deficit affects the verbal or
      the quantity system. Here, we test the association of deficits predicted by this
      theory, and particularly the presence or absence of impairments in non-symbolic
      quantity processing. We describe two acalculic patients, one with a focal lesion
      of the left parietal lobe and Gerstmann's syndrome and another with semantic
      dementia with predominantly left temporal hypometabolism. As predicted by a
      quantity deficit, the first patient was more impaired in subtraction than in
      multiplication, showed a severe slowness in approximation, and exhibited
      associated impairments in subitizing and numerical comparison tasks, both with
      Arabic digits and with arrays of dots. As predicted by a verbal deficit, the
      second patient was more impaired in multiplication than in subtraction, had
      intact approximation abilities, and showed preserved processing of non-symbolic
      numerosities.

PMID- 14572528
TI  - Response inhibition and impulsivity: an fMRI study.
AB  - Aggressive, suicidal and violent behaviour have been associated with impulsive
      personality and difficulty in inhibiting responses. We used functional magnetic
      resonance imaging (fMRI) of the whole brain to examine the neural correlates of
      response inhibition in 19 normal subjects as they performed a Go/NoGo task.
      Subjects completed Eysenck's Impulsivity Scale, Barratt's Impulsivity Scale (BIS)
      and behavioural impulsivity tasks. Associations between blood oxygen level
      dependent (BOLD) response, trait impulsivity, task performance and National Adult
      Reading Test (NART) IQ were investigated. Neural response during response
      inhibition was most prominent in the right lateral orbitofrontal cortex.
      Responses were also seen in superior temporal gyrus, medial orbitofrontal cortex,
      cingulate gyrus, and inferior parietal lobule, predominantly on the right side.
      Subjects with greater scores on impulsivity scales and who made more errors had
      greater activation of paralimbic areas during response inhibition, while less
      impulsive individuals and those with least errors activated higher order
      association areas. Exploratory factor analysis of orbital activations,
      personality measures and errors of commission did not reveal a unitary dimension
      of impulsivity. However, the strong association between posterior orbital
      activation and Eysenck's impulsivity score on a single factor suggests that
      greater engagement of right orbitofrontal cortex was needed to maintain
      behavioural inhibition in impulsive individuals. Lower IQ was more important than
      impulsivity scores in determining errors of commission during the task.
      Neuroimaging of brain activity during the Go/NoGo task may be useful in
      understanding the functional neuroanatomy and associated neurochemistry of
      response inhibition. It may also allow study of the effects of physical and
      psychological interventions on response inhibition in clinical conditions such as
      antisocial personality disorder.

PMID- 14572529
TI  - Factors associated with atypical speech representation in children with
      intractable epilepsy.
AB  - The purpose of this study was to investigate the relationship between hemispheric
      speech dominance and several demographic and seizure variables in a large sample
      of children (N=75) who underwent the intracarotid amobarbital procedure (IAP)
      prior to surgery. The findings were similar to results previously reported in
      adults and children, suggesting that variables, such as age at seizure onset,
      laterality of seizure focus, location of seizure focus and handedness are related
      to the presentation of atypical speech representation in children with epilepsy.
      The impact of multiple variables in determining the risk for atypical speech
      dominance was also assessed. The results demonstrated an increased probability of
      atypical speech representation in children with a greater number of risk
      variables, suggesting the need for further investigations in this area.

PMID- 14572530
TI  - Are planum temporale and sylvian fissure asymmetries directly related? A MRI
      study in great apes.
AB  - In humans and great apes, both the planum temporale (PT-part of Wernicke's area)
      and the sylvian fissure (SF) in the left cerebral hemisphere have been
      consistently shown to be larger than the corresponding structures in the right
      hemisphere. The greater length of the SF in the left hemisphere is commonly
      thought to be a direct consequence of the larger expansion of the PT in the same
      hemisphere. However, there is a lack of studies that have attempted to directly
      assess the tenability of this hypothesis. To address this lack of data, we
      collected magnetic resonance images (MRI) of the brain in 28 apes. The surface
      area of the PT and the length of the pre- and post-central SF were measured in
      each hemisphere using image acquisition and analysis software. In accordance with
      previous findings, the PT was markedly larger in the left hemisphere than in the
      right, and there was also a leftward asymmetry of the SF, particularly of its
      post-central section. However, we found no statistically significant correlation
      between asymmetry of the PT and of the post-central SF, whereas we did find
      evidence of a positive association between asymmetry of the post-central SF and
      of the inferior parietal lobe. These results are congruent with those of a recent
      study with human subjects [Neuropsychiatry, Neuropsychology and Behavioral
      Neurology 12 (1999) 1]. Overall, this converging evidence leads us to question
      the widely accepted notion of a direct relationship between PT and SF asymmetries
      and to consider possible implications of this finding for the study of the
      evolutionary origin of PT asymmetry in primates.

PMID- 14572532
TI  - Why is big Pharma getting out of antibacterial drug discovery?
AB  - Since the advent of the antibiotic era in the late 1940s drug discovery and
      development has evolved into an expensive, time consuming, cumbersome and
      bureaucratic process involving multiple interest groups such as pharmaceutical
      manufacturers, governmental regulatory authorities, patent officers, academic and
      clinical researchers and trial lawyers. It would seem that the least involved
      among the interest groups are the consumers of health care themselves.
      Politicians and the public alike complain loudly about drug prices although fewer
      and fewer new therapies are being developed. The cost and complexities of drug
      discovery and development have shifted the investment equation away from the
      development of drugs targeting short course therapies for acute diseases and
      towards long-term treatment of chronic conditions. Coupled with the failure of
      large investments into target-based approaches to produce novel antibacterial
      agents, companies large and small have exited from this field despite a growing
      clinical need.

PMID- 14572533
TI  - Novel inhibitors of bacterial cell wall synthesis.
AB  - Over the past forty years, efforts to discover antibacterials have yielded a wide
      variety of chemical structures, almost exclusively natural products, which
      inhibit many steps in cell wall synthesis. Although screening for new cell wall
      inhibitors has been continuous during that period, there have been few reports of
      new drugs. With the advent of genomics, high resolution X-ray crystallography and
      the recognition of the need for new antibiotics to combat resistant organisms,
      there has been a resurgence in interest in this validated target area.

PMID- 14572534
TI  - Antibiotics in animal feed and their role in resistance development.
AB  - Animals and humans constitute overlapping reservoirs of resistance, and
      consequently use of antimicrobials in animals can impact on public health. For
      example, the occurrence of vancomycin-resistant enterococci in food-animals is
      associated with the use of avoparcin, a glycopeptide antibiotic used as a feed
      additive for the growth promotion of animals. Vancomycin-resistant enterococci
      and vancomycin resistance determinants can therefore spread from animals to
      humans. The bans on avoparcin and other antibiotics as growth promoters in the EU
      have provided scientists with a unique opportunity to investigate the effects of
      the withdrawal of a major antimicrobial selective pressure on the occurrence and
      spread of antimicrobial resistance. The data shows that although the levels of
      resistance in animals and food, and consequently in humans, has been markedly
      reduced after the termination of use, the effects on animal health and
      productivity have been very minor.

PMID- 14572535
TI  - Multidrug efflux pumps and resistance: regulation and evolution.
AB  - Multidrug transporters have long puzzled researchers because of their ability to
      extrude multiple structurally dissimilar toxic chemotherapeutic agents. They
      appear to be essentially ubiquitous with many microorganisms possessing large
      arsenals of predicted multidrug efflux transporters. Recent reports on the
      structures of multidrug efflux transporters and their cognate regulators have
      suggested that the basis of multidrug recognition is the presence of large
      flexible hydrophobic cavities capable of accommodating different compounds that
      are bound via hydrogen bonding and/or electrostatic interactions. This structural
      data provides the context for understanding other questions about the evolution
      of multidrug transporters and their natural physiological roles.

PMID- 14572536
TI  - Persistence of antibiotic resistant bacteria.
AB  - Bacterial adaptation to antibiotics has been very successful and over the past
      decade the increase in antibiotic resistance has generated considerable medical
      problems. Even though many drug resistances confer a fitness cost, suggesting
      that they might disappear by reducing the volume of antibiotic use, increasing
      evidence obtained from laboratory and epidemiological studies indicate that
      several processes will act to cause long-term persistence of resistant bacteria.
      Compensatory evolution that ameliorates the costs of resistance, the occurrence
      of cost-free resistances and genetic linkage between non-selected and selected
      resistances will confer a stabilization of the resistant bacteria. Thus, it is of
      importance that we forcefully implement strategies to reduce the rate of
      appearance and spread of resistant bacteria to allow new drug discovery to catch
      up with bacterial resistance development.

PMID- 14572537
TI  - Antibiotics and anaerobes of gut origin.
AB  - Hundreds of bacterial species make up human gut flora. Of these, 99% are
      anaerobic bacteria. Although anaerobes are part of the normal commensal flora,
      they can become opportunistic pathogens, causing serious, sometimes fatal
      infections if they escape from the colonic milieu. Most often, this escape occurs
      as a result of perforation, surgery, diverticulitis or cancer. Infections
      involving anaerobic bacteria are often difficult to treat because antibiotic
      resistance is increasing among the genera, mediated primarily through horizontal
      transfer of a plethora of mobile DNA transfer factors. Some of these transfer
      factors can also be transmitted to aerobic bacteria. It is becoming increasingly
      clear that antibiotic resistance trends have to be carefully monitored, and the
      transfer factors and mechanisms of transfer understood at a molecular level to
      avoid negative clinical outcomes when infections involve anaerobic bacteria.

PMID- 14572538
TI  - Therapeutic vaccines against infectious diseases.
AB  - Therapeutic vaccines against chronic infectious diseases aim at eliciting broad
      humoral and cellular immune responses against multiple target antigens.
      Importantly, the development of such vaccines will help to establish surrogate
      markers of protection in humans and thus will augment the subsequent development
      of efficient prophylactic vaccines. A combination of synthetic small-molecule
      drugs and immunotherapeutics is likely to represent a powerful means of
      controlling chronic infections in the future. Challenges faced in developing
      therapeutic vaccines include the following: first, overcoming the potential
      impairment of immune responses due to established infection; second, optimizing
      schedules of vaccine administration in combination with standard of care
      chemotherapy; and third, defining what biological and immunological read-outs
      should be used to infer vaccine efficacy.

PMID- 14572539
TI  - Treatment of infectious diseases with immunostimulatory oligodeoxynucleotides
      containing CpG motifs.
AB  - Bacterial DNA with CpG motifs can efficiently stimulate the vertebrate immune
      system. Thus, synthetic oligodeoxynucleotides that contain such CpG motifs (CpG
      ODN) are currently used in preclinical and clinical studies to develop new
      allergy or cancer therapies and vaccine adjuvants. Recent animal studies indicate
      that CpG-ODN therapies can also be used for successful treatment of infections
      caused by bacteria, parasites or viruses. In these experiments, innate and
      adaptive immune responses against pathogens were augmented by CpG-ODN and
      subsequently induced resistance against infectious diseases. The stimulation of
      dendritic cells played a central role for the therapeutic effect of CpG-ODN.
      However, CpG-ODN can also have negative side effects, which accelerate disease
      progression in some viral infections. Clinical studies with CpG-ODN will
      determine their potential for the therapy of infectious diseases in humans.

PMID- 14572540
TI  - Genomics. A global view of gene gain, loss, regulation and function.

PMID- 14572541
TI  - Identifying global regulators in transcriptional regulatory networks in bacteria.
AB  - The machinery for cells to take decisions, when environmental conditions change,
      includes protein-DNA interactions defined by transcriptional factors and their
      targets around promoters. Properties of global regulators are revised attempting
      to reach diagnostic explicit criteria for their definition and eventual future
      computational identification. These include among others, the number of regulated
      genes, the number and type of co-regulators, the different sigma-classes of
      promoters and the number of transcriptional factors they regulate, the size of
      the evolutionary family they belong to, and the variety of conditions where they
      exert their control. As a consequence, global versus local regulation can be
      identified, as shown for Escherichia coli and eventually in other genomes.

PMID- 14572542
TI  - Evolutionary connections between bacterial and eukaryotic signaling systems: a
      genomic perspective.
AB  - Recent advances in microbial genomics suggest that several protein domains are
      common to bacterial and eukaryotic regulatory proteins. In particular,
      developmentally and morphologically complex prokaryotes appear to share several
      signaling modules with eukaryotes. New experimental studies and information from
      domain architectures point to several similar mechanistic themes in bacterial and
      eukaryotic signaling proteins. Laterally transferred protein domains, originally
      of bacterial provenance, appear to have contributed to the evolution of sensory
      pathways related to light, redox and nitric oxide signaling, and developmental
      pathways, such as Notch, cytokine and cytokinin signaling in eukaryotes.

PMID- 14572543
TI  - Horizontal gene transfer and phylogenetics.
AB  - The initial analysis of complete genomes has suggested that horizontal gene
      transfer events are very frequent between microorganisms. This could potentially
      render the inference, and even the concept itself, of the organismal phylogeny
      impossible. However, a coherent phylogenetic pattern has recently emerged from an
      analysis of about a hundred genes, the so-called 'core', strongly suggesting that
      it is possible to infer the phylogeny of prokaryotes. Also, estimation of the
      frequency of horizontal gene transfers at the genome level in a phylogenetic
      context seems to indicate that it is rather low, although of significant
      biological impact. Nevertheless, it should be emphasized that the history of
      microorganisms cannot be properly represented by the phylogeny of the core, which
      represents only a tiny fraction of the genome. This history, even if horizontal
      gene transfers are rare, should be represented by a network surrounding the core
      phylogeny.

PMID- 14572544
TI  - Bacteriophage genomics.
AB  - Comparative genomic studies of bacteriophages, especially the tailed phages,
      together with environmental studies, give a dramatic new picture of the size,
      genetic structure and dynamics of this population. Sequence comparisons reveal
      some of the detailed mechanisms by which these viruses evolve and influence the
      evolution of their bacterial and archaeal hosts. We see rampant horizontal
      exchange of sequences among genomes, mediated by both homologous and
      nonhomologous recombination. High frequency exchange among phages occupying
      similar ecological niches leads to a high degree of mosaic diversity in local
      populations. Horizontal exchange also takes place at lower frequency across the
      entire span of phage sequence space.

PMID- 14572545
TI  - Tracing the evolution of gene loss in obligate bacterial symbionts.
AB  - The gamma-proteobacterial symbionts of insects are a model group for comparative
      studies of genome reduction. The phylogenetic proximity of these reduced genomes
      to the larger genomes of well-studied free-living bacteria has enabled
      reconstructions of the process by which genes and DNA are lost. Three genome
      sequences are now available for Buchnera aphidicola. Analyses of Buchnera genomes
      in comparison with those of related enteric bacteria suggest that extensive
      changes including large deletions, repetitive element proliferation and
      chromosomal rearrangements occurred initially, followed by extreme stasis in gene
      order and slow decay of additional genes. This pattern appears to be
      characteristic of symbiont evolution.

PMID- 14572546
TI  - Genomic analysis of secretion systems.
AB  - Secretion of proteins into the extracellular environment is important to almost
      all bacteria, and in particular mediates interactions between pathogenic or
      symbiotic bacteria with their eukaryotic hosts. The accumulation of bacterial
      genome sequence data in the past few years has provided great insights into the
      distribution and function of these secretion systems. Three systems are
      responsible for secretion of proteins across the bacterial cytoplasmic membrane:
      Sec, SRP and Tat. Many novel examples of systems for transport across the Gram
      negative bacterial cell envelope have been discovered through genome sequencing
      and surveys, including many novel type III secretion systems and
      autotransporters. Similarly, genomic data mining has revealed many new potential
      secretion substrates and identified unsuspected domains in secretion-associated
      proteins. Interestingly, genomic analyses have also hinted at the existence of a
      dedicated protein secretion system in Gram-positive bacteria, targeting members
      of the WXG100/ESAT-6 family of proteins, and have revealed an unexpectedly wide
      distribution of sortase-driven protein-targeting systems.

PMID- 14572547
TI  - Serological studies of monoclonal RH antibodies with RH1 (D), RH2 (C), RH3 (E)
      and RH5 (e) variant RBCs.
AB  - One hundred and forty five Mabs against RH antigens were tested. In this paper,
      we chose to detail reactivity of MoAbs directed against variant RBCs of the CNRGS
      collection for which we studied the molecular background. Because we developed
      procedures to identify variants of the RhD, RhC, RhE and Rhe antigens, we were
      especially interested in finding new monoclonal antibodies that could help us to
      characterize more accurately these variants. Therefore, we drew parallels between
      our procedures and results obtained with the 2001 workshop antibodies.

PMID- 14572548
TI  - [Evaluation of adherence to the regulations for declaration of notification of
      transfusion reactions with fever and chills. A study of the Association Inter
      Regionale du Sud-Est d'Hemovigilance (AIRSEH)].
AB  - Febrile non-hemolytic transfusion reactions (FNHTR) are the most frequently
      reported acute adverse effects of blood products, and should be notified within
      48 h according to the hemovigilance regulation. In order to study the conformity
      of these notifications and to search for factors associated with non-conformity,
      we retrospectively studied all FNHTR notified by voluntary centers of the AIRSEH
      group from 1st September 1994 to 31st December 1999. Seven hundred and sixty-one
      FNHTR were registered by 10 centers, most of them were benign (grade 1); 67.8%
      were non-conform. The non-conformity was associated with the number of biological
      investigations performed (median number, respectively, 4.24 and 2.94--P = 0.038-
      in non-conform and conform notifications--P = 0.038) in univariate analysis.
      Using a logistic regression model, center and severity were the only two factors
      significantly associated with non-conformity. Different center practices, and in
      particular the interface between the hospital and the blood bank, may be
      responsible for the effect center. Moreover, the non-conformity concerns first of
      all benign FNHTR. A stronger separation between alert and epidemiological
      surveillance is proposed in order to improve the notifications' conformity.

PMID- 14572549
TI  - [The ABO system polymorphism in Tunisian blood donors].
AB  - The present survey was carried out in the Military Center of Blood Transfusion
      from January 1998 to December 2001. 63,375 blood donors were concerned coming
      from different regions of Tunisia. Gene frequencies were found as follows: O =
      0.686, A = 0.196 and B = 0.120. Important variations are observed between
      different regions of the country. The comparison with other countries' results
      traces the history of the Tunisian population, Tunisia being a strategic point in
      the Mediterranean region.

PMID- 14572550
TI  - [Application of molecular biology techniques to malignant haematology].
AB  - Malignant hemopathies, although heterogeneous in their prognosis and oncogenesis,
      represent an interesting model for studying cancer genesis mechanisms in man
      through the recurrent presence of genetic abnormalities involved in oncogenesis
      and the availability of tumour material. Nowadays, molecular biology techniques
      are very much used for the diagnosis, the treatment and the follow-up of these
      diseases. Firstly used for research, the new techniques have completely changed
      our ability to characterise malignant hemopathies and to understand the cancer
      inducing processes, permitting us to perform the biological assessment of
      patients with malignant hemopathies, the diagnosis, and to estimate and follow
      the outcome of patients after treatment. At a more fundamental level, the
      structural and functional analysis of the deregulated genes implied in leukaemia
      and lymphoma has improved our knowledge and understanding of oncogenic and
      physiologic mechanisms significantly.

PMID- 14572551
TI  - [Haemovigilance in the health care establishment: its role in pediatric
      transfusion].
AB  - Haemovigilance, an important step in transfusion safety, had been set up by a
      French law in January 1993. Application of haemovigilance in public hospitals is
      based on three conditions: reporting of adverse transfusion events, traceability
      of blood products and prevention of adverse transfusion events. The
      implementation of haemovigilance follows the rules given in a Ministry order
      dated January 1994, the first of a series including regulations about patient
      information, virological follow-up of transfused patients, blood product
      distribution. Haemovigilance rules are the same for adults as for children,
      concerning blood product traceability and adverse event reporting. It is much
      more difficult in other fields such as autologous transfusion and "child-patient"
      information that depend on their parent advice and should be particularly adapted
      to the familial context, the type of disease and the treatment. Difficulties
      arise for completing pre- and post-transfusion, immuno-haematologic and virologic
      controls. Compliance to protocols, in agreement with blood banks, is necessary.

PMID- 14572552
TI  - AIDS cholangiopathy: "an endangered disease".

PMID- 14572553
TI  - Stress and ulcerative colitis: convincing the doubting Thomases.

PMID- 14572554
TI  - Chronic HBV without e antigen: using HBV DNA to guide management.

PMID- 14572555
TI  - A systematic review of surgical therapy for gastroparesis.
AB  - Gastroparesis is characterized by delayed gastric emptying in the absence of
      obstruction. Common symptoms include nausea, vomiting, and abdominal pain. Severe
      gastroparesis might result in recurrent hospitalizations, malnutrition, and
      significant mortality. Patients failing medical therapy are often considered for
      a variety of surgical interventions, the efficacy of which is not well studied.
      This review summarizes available literature on surgical interventions in
      gastroparesis. A MEDLINE search for the period from 1966 to 2002 was performed to
      identify all English language literature regarding surgical interventions in
      gastroparesis. Therapies reviewed were gastrostomy, jejunostomy, gastric
      pacing/stimulation, and gastrectomy or surgical drainage procedures. Candidate
      studies involved human subjects and included surgical series or trials. The
      search was conducted independently by two authors and discrepancies resolved by
      consensus opinion. Seventeen articles met inclusion criteria. These included
      series reporting on gastrostomy (2), jejunostomy (3), gastric stimulation (2),
      and gastrectomy for postsurgical (6), diabetic (3), and idiopathic (1)
      gastroparesis. All trials were unblinded, uncontrolled case series or
      retrospective reviews. Methodologic differences did not allow for pooled
      analysis. Completion gastrectomy seems to provide symptom relief in postsurgical
      gastroparesis. Benefits of gastric surgery for other forms of gastroparesis are
      not adequately studied. Gastrostomy might provide symptom improvement, but only
      26 subjects in two trials were evaluable. Jejunostomy improved symptoms and
      nutrition in 32 evaluable subjects in three trials but had significant
      complications. Gastric neurostimulation improves symptoms of nausea and vomiting,
      but therapeutic gain beyond placebo has not been demonstrated. Limited data exist
      concerning surgical therapies of gastroparesis. Completion gastrectomy seems
      effective for postsurgical gastroparesis, but a cautious approach is warranted
      before surgical therapies in diabetic or idiopathic gastroparesis are used.

PMID- 14572556
TI  - Triple infection with human immunodeficiency virus, hepatitis C virus, and
      hepatitis B virus: a clinical challenge.

PMID- 14572557
TI  - The caring physician: a journey in self-exploration and self-care.
AB  - Caring for patients involves empathic listening and awareness of the needs and
      feelings of the patient as well as our own; the acceptance of the fallibilities
      of medicine and ourselves. Too often we lead unbalanced lives in terms of work,
      relationships, play and personal time. We frequently strive for perfection, deny
      our needs and feelings, assume total responsibility for the patient, and are
      altruistic to the point of self-denial. Caring for patients without adequately
      caring for ourselves is frequently associated with subconscious needs for
      external validation. The hidden agenda may be harmful to the patient and the
      physician. Change requires self-awareness and recognition of the overt and covert
      benefits and risk of our current work patterns. Often there is a need to
      reexamine our life priorities, set limits at work, admit vulnerability, share our
      emotional lives, and appreciate the small things in our daily life that give us
      meaning and purpose.

PMID- 14572558
TI  - Belching: dyspepsia or gastroesophageal reflux disease?
AB  - OBJECTIVES: Eructation (belching) is a common symptom seen in clinical practice.
      Because either belching or heartburn may result from transient lower esophageal
      sphincter relaxations, it has been proposed that belching may be a manifestation
      of gastroesophageal reflux disease (GERD). In this retrospective study we
      evaluated the prevalence of belching in dyspepsia and GERD and the relation of
      belching to acid reflux events documented by pH monitoring. METHODS: We examined
      the prevalence, frequency, and severity of belching and other GERD symptoms by
      use of standardized questionnaires in 180 GERD patients (group A) and 78
      dyspeptic controls (group B) referred for evaluation at our institution. GERD was
      defined as either endoscopic esophagitis (or Barrett's esophagus) or positive
      DeMeester score (>14.2) on pH monitoring or both. Dyspeptic patients had normal
      endoscopy and pH studies. We also analyzed the relationship of belching to acid
      reflux events during the 24-h period of pH studies. RESULTS: Of 180 GERD
      patients, 132 (70%) reported belching during pH monitoring, versus 63 of 78
      dyspeptic patients (80%) (p = ns). Similarly, 163 of 180 GERD patients (90%)
      reported heartburn versus 64 of 78 of dyspeptic patients (82%) (p = ns). Review
      of symptom questionnaires revealed no significant difference in belching severity
      between groups. However, heartburn and acid regurgitation were significantly more
      severe among GERD patients. There was a significantly higher correlation of both
      heartburn and belching with acid events in patients with GERD compared with
      patients with dyspepsia. In addition, although both belching and heartburn were
      significantly improved in patients with GERD, belching scores remained unchanged
      after proton pump inhibitor (PPI) therapy in patients with dyspepsia.
      CONCLUSIONS: Belching is as common and as severe in patients with dyspepsia as it
      is in patients with GERD. Belching and heartburn in GERD patients are more likely
      correlated with episodes of pathological acid reflux. Because belching cannot be
      clinically used as a discriminatory symptom, ambulatory pH monitoring should be
      considered to elucidate the relationship of belching to acid reflux in patients
      with dyspepsia or GERD.

PMID- 14572559
TI  - Prevalence of esophageal candidiasis among patients treated with inhaled
      fluticasone propionate.
AB  - OBJECTIVES: Development of oropharyngeal candidiasis is a frequently reported
      adverse effect of inhaled corticosteroid use, but the prevalence of esophageal
      candidiasis is unknown. The aim of this study was to estimate the prevalence of
      esophageal candidiasis among patients treated with an inhaled corticosteroid,
      fluticasone propionate. METHODS: Upper GI endoscopy was performed on 49 patients
      treated with inhaled fluticasone propionate to examine the prevalence of
      esophageal candidiasis. Of the patients, 36 had bronchial asthma and 13 had
      chronic obstructive pulmonary disease. To compare the prevalence with control
      patients, upper GI endoscopy was performed on 700 consecutive patients without
      malignancy or immunosuppression. RESULTS: The prevalence of esophageal
      candidiasis was 37% among patients treated with inhaled fluticasone propionate,
      whereas only 0.3% of the control patients had the infection. The prevalence was
      especially high among patients with diabetes mellitus or those who were treated
      with a high dose of inhaled fluticasone propionate. Moreover, a reduction in the
      daily dose of inhaled fluticasone propionate eliminated the infection in four of
      five patients. CONCLUSIONS: Esophageal candidiasis is a common complication of
      inhaled corticosteroid use.

PMID- 14572560
TI  - Eradication of Helicobacter pylori improves the healing rate and reduces the
      relapse rate of nonbleeding ulcers in patients with bleeding peptic ulcer.
AB  - OBJECTIVE: A causal relationship between Helicobacter pylori (H. pylori) and
      peptic ulcer complications remains obscure. The aim of this study was to
      determine the importance of H. pylori and other risk factors for healing rate,
      ulcer recurrence, and rebleeding in patients with bleeding peptic ulcer. METHOD:
      A total of 223 patients with H. pylori positive bleeding peptic ulcer were
      randomly allocated to three treatment groups: 1) quadruple therapy (QT) (88
      patients); 2) dual therapy (DT) (88 patients); and 3) omeprazole and placebo
      therapy (OPl) (47 patients). Endoscopic assessment was performed initially and at
      8 and 52 wk. Ulcer healing and eradication rates were assessed; endpoints were
      ulcer relapse and ulcer rebleeding during 52 wk. RESULTS: Results after 8 and 52
      wk were available for 211 and 179 patients, respectively. Eradication rate was
      100% (95% CI = 96-100%) in the QT, 84% (95% CI = 74-91%) in the DT, and 4% (95%
      CI = 1-15%) in the OPl group. Ulcer healing rate was 95% (95% CI = 91-98%) in H.
      pylori negative and 8% (95% CI = 70-91%) in H. pylori positive patients. Ulcer
      relapses occurred in 2% (95% CI = 0.5-6%) of H. pylori negative and in 38% (95%
      CI = 24-54%) of H. pylori positive patients, and rebleeding occurred in five
      patients (three H. pylori positive and two negative). CONCLUSIONS: Eradication of
      H. pylori infection enhances healing of bleeding peptic ulcers after endoscopic
      therapy. H. pylori infection is an important independent risk factor for
      relapsing of nonbleeding ulcers in patients with bleeding peptic ulcer.

PMID- 14572561
TI  - Susceptibility of Helicobacter pylori to metronidazole.
AB  - OBJECTIVES: The reliability of the Epsilometer-test (E-Test) and the disk
      diffusion (DD) method in the assessment of susceptibility of Helicobacter pylori
      (H. pylori) to metronidazole has recently been questioned, with possible clinical
      implications for the management of patients undergoing H. pylori eradication. The
      aims of this study were: 1) to compare the E-Test and disk diffusion methods to
      the agar dilution method for determining the susceptibility of H. pylori to
      metronidazole; and 2) to investigate whether potential discrepancies could be
      caused by the simultaneous presence of metronidazole susceptible and
      metronidazole resistant bacterial subpopulations. METHODS: A total of 109 H.
      pylori strains from 121 consecutive patients were examined. All tests were
      carried out at the same time starting from primary plates. Agar dilution was
      performed according to National Committee for Clinical Laboratory Standard
      (NCCLS) standards, the E-Test according to the manufacturer's guidelines, and
      disk diffusion according to standard procedure using 5-mug metronidazole disks.
      Isolates were considered to be metronidazole resistant if the minimal inhibitory
      concentration was >8 mug/ml for the agar dilution and the E-Test, or if the
      inhibition zone around the disk was <20 mm for disk diffusion. Of 109 isolates,
      43 were also investigated to detect mixed infection. Quantities of 100 mul of
      bacterial suspensions of each strain were seeded onto plain agar plates and
      plates containing 8 mug/ml of metronidazole. Cultures were considered to be mixed
      if the number of colonies on agar plates exceeded by at least 30% those on the
      metronidazole plates. RESULTS: According to agar dilution, 57 strains (52.3%, 95%
      CI = 43-61.4) were metronidazole resistant. E-Test misdiagnosed two strains that
      were considered sensitive to metronidazole, but according to the agar dilution
      test they were resistant. Disk diffusion misdiagnosed three strains. Two of these
      strains (the same as the E-Test) were sensitive, but according to agar dilution
      they were metronidazole resistant; the third strain was resistant, but according
      to agar dilution it was sensitive. The percentages of discordance were 1.9 (95%
      CI = 0.5-6.6) and 2.8 (95% CI = 0.9-7.8), respectively, when the E-Test and disk
      diffusion were compared to agar dilution. Intertest variability among agar
      dilution and the E-Test showed that 39.4% (95% CI = 30.8-48.8) of minimal
      inhibitory concentrations were equivalent (within +/-1 log(2)), 60.6% (95% CI =
      51.2-69.2) were major errors (more than +/-1 log(2)), and 3% (95% CI = 0.8-10.4)
      were very major errors (change in susceptibility pattern). Mixed infection was
      found in six of the 43 cases examined (13.9%). In four cases, metronidazole
      resistant strains were 1 log(10) less numerous than those that were metronidazole
      susceptible. In the remaining two cases, the metronidazole resistant strains were
      2-3 log(10) less numerous, which caused the two misdiagnoses. CONCLUSIONS: The E
      Test and disk diffusion method are very good alternatives to agar dilution. Mixed
      infections are a possible cause of the discrepancies between these tests and the
      reference method.

PMID- 14572562
TI  - The seroprevalence of Helicobacter pylori in a referral population of children in
      the United States.
AB  - OBJECTIVES: The purpose of this study was to determine the prevalence of serum
      antibodies directed against Helicobacter pylori (H. pylori) in children referred
      to children's hospitals or medical centers throughout the United States. METHODS:
      This multisite cross-sectional prospective study involved 992 children from 12
      states using a validated anti-H. pylori IgG enzyme immunoassay. The children were
      recruited into two groups: those without any GI complaints (non-GI referral, n =
      619) and those who were referred for endoscopy because of abdominal pain (GI
      referral, n = 373). RESULTS: GI referral children had a higher rate of
      seropositivity (22.5%) than non-GI referral children (14.1%) from the same
      geographic regions. In both groups, older children were more likely to be
      seropositive for H. pylori, as were nonwhite children and those with lower
      socioeconomic status. H. pylori seropositivity rates were higher in GI referral
      children with four or more household members (relative risk [RR] = 1.47; CI 1.01
      2.14). Multivariate analysis controlling for age, ethnicity, and household
      income, showed that presence of GI symptoms were associated with a nearly 2-fold
      risk for H. pylori seropositivity (odds ratio = 1.77, CI 1.27-2.47). Epigastric
      pain (RR = 2.21; CI = 1.33-3.66) and having three or more episodes of abdominal
      pain in the last 3 months (RR = 0.59, CI = 0.35-0.99) were the only specific
      symptoms significantly associated with H. pylori seropositivity. CONCLUSIONS: The
      H. pylori seropositivity rate of GI referral children with symptoms of abdominal
      pain was significantly higher. H. pylori infection in early childhood was found
      to be associated primarily with the child's household size and socioeconomic
      status.

PMID- 14572563
TI  - Unsuppressed postprandial phasic contractility in the proximal stomach in
      functional dyspepsia: relevance to symptoms.
AB  - OBJECTIVES: Phasic fundic contractions induce transient increases in gastric wall
      tension and can be perceived in patients with functional dyspepsia. It is unclear
      whether phasic contractile activity contributes to postprandial symptoms. The aim
      of the study was to examine postprandial phasic contractility in functional
      dyspepsia in relation to pathophysiological, clinical, and demographic variables.
      METHODS: A gastric barostat study was performed in 180 patients with functional
      dyspepsia and in 53 healthy control subjects. Sensitivity to distensions and the
      motor response to a standardized liquid meal were assessed. Phasic contractility
      in the proximal stomach was quantified using a motility index during three 30-min
      periods, namely, the preprandial period and the first and second postprandial
      periods. Unsuppressed phasic contractility after the meal was defined as motility
      index greater than mean + 2 SD in control subjects in at least one of the two
      postprandial periods. Relationships between unsuppressed phasic contractility and
      impaired accommodation, hypersensitivity, delayed gastric emptying, Helicobacter
      pylori (H. pylori) infection, symptom severity, and demographic factors were
      assessed. RESULTS: Patients demonstrated a higher motility index than did control
      subjects during the first (22.8 +/- 10.1 vs 20.3 +/- 6.8 ml/s; p = 0.04) but not
      the second (19.9 +/- 9.1 vs 18.7 +/- 6.9 ml/s; ns) postprandial 30-min period.
      The motility index before the meal was similar in patients and controls.
      Unsuppressed phasic contractility postprandially was observed in 15% of the
      patients. H. pylori infection (p = 0.01), relevant or severe bloating (p =
      0.004), and absence of nausea (p = 0.004) were found to be independently
      associated with unsuppressed phasic contractility after a meal. CONCLUSIONS:
      Unsuppressed postprandial phasic contractility in the proximal stomach is present
      in a small subset of patients with functional dyspepsia. It is associated with
      relevant and severe bloating and H. pylori infection but also with the absence of
      nausea.

PMID- 14572564
TI  - Prognostic factors for the survival of patients with AIDS cholangiopathy.
AB  - OBJECTIVES: AIDS cholangiopathy, once considered to have extremely poor
      prognosis, is now rarely fatal. This study was designed to assess the survival of
      patients with AIDS cholangiopathy and investigate prognostic variables,
      especially in the era of highly active antiretroviral therapy (HAART). METHODS:
      Ninety-four patients with AIDS cholangiopathy were diagnosed at the San Francisco
      General Hospital from 1983 to 2001. The mortality status, demographic and
      clinical variables, and ERCP results were collected through death certificates,
      chart review, and endoscopic reports. RESULTS: The median survival time from the
      diagnosis of AIDS and AIDS cholangiopathy was 23 and 9 months, respectively.
      HAART significantly improved the mortality of patients with AIDS cholangiopathy
      (hazard ratio [HR] = 0.08, 95% confidence interval [CI] = 0.02-0.35). The
      presence or history of any opportunistic infection involving the digestive tract,
      lung, eye, nervous system, skin, or systemic involvement at the time when AIDS
      cholangiopathy was diagnosed was an indicator of poor prognosis (HR = 3.24, 95%
      CI = 1.45-7.26); this was especially true for cryptosporidial infection (HR =
      2.05, 95% CI = 1.24-3.38). Patients with high serum ALP levels, especially
      greater than 1000 IU/L or eight times the normal value (HR = 2.69, 95% CI = 1.10
      6.60), tended to have a shorter life expectancy than those with normal or
      slightly elevated serum ALP levels. CD4 lymphocyte counts, type of
      cholangiopathy, and the performance of sphincterotomy were not correlated with
      the survival of patients with AIDS cholangiopathy. CONCLUSIONS: HAART
      administration most likely accounts for the recent dramatic improvement in
      survival of patients with AIDS cholangiopathy. Underlying immunosuppressive
      status, reflected by the presence or history of any opportunistic infections, is
      associated with a worse outcome. Serum ALP levels might be a good clinical
      indicator for the prognosis of patients with AIDS cholangiopathy.

PMID- 14572565
TI  - Comparison of two dosing regimens of gabexate in the prophylaxis of post-ERCP
      pancreatitis.
AB  - OBJECTIVES: A continuous 13-h infusion of gabexate starting 30-90 min before
      endoscopic cholangiopancreatography (ERCP) can reduce postprocedural
      pancreatitis, the onset of which is generally observed within the first 6 h after
      ERCP. This study was designed to verify whether a 6.5-h infusion of gabexate was
      as effective as a 13-h infusion, at the same concentration, for reducing the
      incidence of post-ERCP pancreatitis (primary endpoint) and pancreatic
      hyperenzymemia and pain (secondary endpoints). METHODS: A total of 434 patients
      (201 male and 233 female; mean age 63.9 yr, range 18-96 yr) scheduled for ERCP
      were prospectively recruited in 25 Italian centers. Patients were randomized
      double-blind to two treatment groups. All subjects enrolled were first treated
      with a 500-mg continuous intravenous infusion of gabexate, starting 30 min before
      the endoscopic maneuvers and continuing up to 6.5 h after it. Over the next 6.5
      h, 214 patients (group I) continued the infusion of gabexate (for a total of 1 g
      over 13 h) and 220 patients (group II) were given placebo (saline solution).
      RESULTS: The overall incidence of acute pancreatitis was 1.8% (eight patients),
      which included 1.4% in group I (three of 214 patients) and 2.2% in group II (five
      of 220 patients). Serum amylase and lipase values over time, peak levels of the
      two enzymes, pancreatic pain, and need for analgesics did not significantly
      differ in the two groups. CONCLUSIONS: These results suggest that a 6.5-h
      infusion of gabexate (for a total of 500 mg) is not less effective than a 13 h
      infusion, with evident savings.

PMID- 14572566
TI  - Comparison of reduced volume versus four liters sulfate-free electrolyte lavage
      solutions for colonoscopy colon cleansing.
AB  - OBJECTIVE: In an attempt to improve patient tolerance for colonoscopy cleansing,
      a reduced volume lavage regimen with 2 L sulfate-free electrolyte lavage solution
      (SF-ELS, NuLYTELY, Braintree Laboratories, Braintree, MA) plus 20 mg p.o.
      bisacodyl (Half Lytely, Braintree Laboratories) was compared with standard 4 L SF
      ELS lavage for safety and efficacy. METHODS: At two centers, 200 patients
      undergoing colonoscopy for routine indications were randomized to receive the
      reduced volume or standard 4 L method. The day before scheduled colonoscopy,
      study subjects were allowed a normal breakfast and clear liquids for lunch and
      dinner. Those randomized to receive the reduced volume method received four 5-mg
      bisacodyl tablets p.o. at noon. Six hours later, they received 2 L SF-ELS given
      as 10 oz every 10 min. Subjects randomized to receive 4 L SF-ELS also drank their
      solution at 6:00 PM in a similar fashion. Colonoscopists, unaware as to the
      randomized preparation received, rated efficacy of cleansing. Patient tolerance
      and various hematological and biochemical parameters were assessed. RESULTS:
      Physician assessment of colon cleansing showed no differences between those
      patients randomized to receive reduced volume (n = 93) or 4 L (n = 93) SF-ELS
      cleansing (p = 0.16). There was a profound reduction in preparation side effects.
      The reduced volume preparation had less fullness (p < 0.01), nausea (p < 0.01),
      vomiting (p = 0.01), and overall discomfort (p < 0.01). There were no clinically
      significant changes in hematology or blood chemistry associated with either
      preparation. CONCLUSIONS: Reduced volume preparation with 2 L SF-ELS and
      bisacodyl is safe and effective. Clinical symptoms from the reduced volume
      preparation are significantly reduced compared with traditional 4 L gut lavage.

PMID- 14572567
TI  - A prospective, randomized comparison of 10-Fr versus 7-Fr bipolar
      electrocoagulation catheter in combination with adrenaline injection in the
      endoscopic treatment of bleeding peptic ulcers.
AB  - OBJECTIVES: Our study compared the efficacy of bipolar electrocoagulation (gold
      probe) with 10-Fr (group A) versus 7-Fr (group B) catheter after adrenaline
      injection in the treatment of bleeding peptic ulcers. METHODS: A total of 77
      consecutive patients with endoscopic evidence of peptic ulcer with active
      bleeding or a nonbleeding visible vessel were randomly assigned to one of the
      above protocols. Thirty-nine patients (31 male, eight female, mean age 62 yr)
      were included in group A and 38 (28 male, 10 female, mean age 61 yr) in group B.
      RESULTS: The initial hemostasis rate, rebleeding rate, duration of hospital stay,
      volume of blood transfused, number of operations needed, and number of deaths
      were not significantly different between the two groups. The mean number of
      electrocoagulations and the subsequent mean duration of electrocoagulations were
      significantly higher in group B patients (7.0 +/- 3.8 and 14.1 +/- 7.6 s,
      respectively) compared with those of group A (4.6 +/- 2.6 and 9.3 +/- 5.3 s,
      respectively) (p < 0.01). Multivariate stepwise logistic regression analysis
      revealed that among sex, age, location of bleeding, ulcer size, endoscopic
      severity of bleeding, and the size of the gold probes, lesser endoscopic severity
      of bleeding (chi(2) = 31.1, p < 0.01), large size of the gold probe (chi(2) =
      23.9, p < 0.01), and small ulcer size (chi(2) = 13.4, p < 0.01) were the only
      factors significantly associated with a smaller number of electrocoagulations.
      CONCLUSIONS: In this study, the use of large-size gold probes was significantly
      associated with a lower number of electrocoagulations, resulting in the reduction
      of electrocoagulation duration. However, the clinical relevance of these findings
      is questionable because the efficacy of both sizes of gold probe after adrenaline
      injection in the treatment of bleeding peptic ulcers was similar.

PMID- 14572568
TI  - Evaluation of endoscopic hemostasis with metallic hemoclips for bleeding gastric
      ulcer: comparison with endoscopic injection of absolute ethanol in a prospective,
      randomized study.
AB  - OBJECTIVE: Although metallic hemoclips have been used for hemostasis of bleeding
      ulcer, there have been few prospective trials to evaluate their efficacy. In this
      study, a prospective, randomized trial was performed to evaluate endoscopic
      hemoclipping for bleeding gastric ulcer in comparison with endoscopic injection
      of absolute ethanol. METHODS: During the period 1995-1998, 126 gastric ulcer
      patients with bleeding or nonbleeding visible vessel were considered for entry.
      They were randomly assigned to one of three groups: endoscopic hemostasis
      performed with injection of absolute ethanol (group I, n = 42), hemoclipping
      (group II, n = 42), and a combination of the two methods (group III, n = 42).
      RESULTS: The permanent hemostatic rate was 85.7% in group I, 90.5% in group II,
      and 92.9% in group III. The mean volume of blood transfusion was 313 +/- 77 ml in
      group I, 274 +/- 54 ml in group II, and 163 +/- 42 ml in group III, which was
      significantly less than in groups I or II (p < 0.05). No patients required
      emergency surgery. Five patients died within a month after initial hemostasis as
      a result of unrelated conditions. CONCLUSIONS: Endoscopic hemostasis with
      hemoclips for bleeding gastric ulcer was as effective and safe as that with
      injection of absolute ethanol, and a combination of ethanol injection and
      hemoclips did not result in a great advantage over the two individual procedures.

PMID- 14572569
TI  - Psychosocial determinants of relapse in ulcerative colitis: a longitudinal study.
AB  - OBJECTIVES: To determine the association between psychosocial characteristics and
      time to relapse in patients with inactive ulcerative colitis. METHODS: Sixty
      patients with clinically and endoscopically inactive ulcerative colitis were
      followed for 1 yr, or less if they relapsed. Demographic, psychosocial, and
      clinical data were obtained. Stressful life events (Psychiatric Epidemiology
      Research Interview Life Events Scale), psychological distress (Symptom Checklist
      90R), and perceived stress (Perceived Stress Scale) were recorded monthly by self
      report. Multivariate time-dependent Cox regression was used to identify the
      independent determinants of earlier time to clinical relapse. RESULTS: The
      patients' mean age was 39 yr (SD = 9.4), 37 (62%) were female, and 22 (37%)
      relapsed during the 1-yr follow-up. Univariate Cox regression indicated a weak
      association between number of stressful events in the preceding month and time to
      relapse (p = 0.09). This association strengthened in multivariate analysis (p =
      0.02, hazard ratio = 1.26 per event, 95% CI = 1.04-1.53) after adjustment for
      significant covariates. CONCLUSIONS: After controlling for demographic and
      clinical variables, more recent stressful events were associated with earlier
      time to relapse. These findings, which support a biopsychosocial model of
      disease, might help clinicians identify patients who might benefit from more
      intensive maintenance medical therapy and behavioral medicine interventions to
      reduce stress and improve coping.

PMID- 14572570
TI  - A randomized controlled trial of cognitive behavior therapy, relaxation training,
      and routine clinical care for the irritable bowel syndrome.
AB  - OBJECTIVES: Psychological treatments are considered to be useful in the irritable
      bowel syndrome (IBS), although the evidence is based on small, often flawed
      trials. Although cognitive behavior therapy (CBT) and relaxation therapy have
      both been promising, we hypothesized that CBT would be superior to relaxation and
      standard care alone in IBS patients. The objective of this study was to test this
      assumption by comparing the effects of cognitive behavior therapy with relaxation
      therapy and routine clinical care alone in individuals with IBS. METHODS:
      Patients (n = 105) with Rome I criteria for IBS were recruited from advertisement
      (n = 51) and outpatient clinics (n = 54); those patients with resistant IBS were
      not included. A randomized controlled trial with three arms (standard care for
      all groups plus either CBT or relaxation) for 8 wk was conducted, which applied
      blinded outcome assessments using validated measures with 1 yr of follow-up. The
      primary outcome for this study was bowel symptom severity. RESULTS: Of 105
      patients at the commencement of treatment, the mean bowel symptom frequency score
      for the whole sample was 21.1 and at the end of treatment had fallen to 18.1;
      this persisted at the 52-wk follow-up, with a significant linear trend for scores
      to change over time (F = 39.57 p < 0.001). However, there were no significant
      differences among the three treatment conditions. Significant changes over time
      were found for physical functioning (F = 4.37, p < 0.001), pain (F = 3.12, p <
      0.05), general health (F = 2.71, p < 0.05), vitality (F = 2.94, p < 0.05), and
      the social functioning scales on the Medical Outcomes Study Short Form 36 (F =
      4.08, p < 0.05); however, all three arms showed similar improvement. There were
      significant reductions in anxiety, depression, and locus of control scales, but
      no significant differences among the treatment groups were detected. CONCLUSION:
      Cognitive behavior and relaxation therapy seem not to be superior to standard
      care alone in IBS.

PMID- 14572571
TI  - Rapid intestinal transit as a primary cause of severe chronic diarrhea in
      patients with amyloidosis.
AB  - OBJECTIVE: The cause of severe diarrhea in patients with systemic amyloidosis is
      obscure. We therefore performed pathophysiological studies in three such patients
      in an effort to determine the mechanism of amyloid diarrhea. METHODS: Epithelial
      cell absorption rate of electrolytes was measured during steady state GI
      perfusion of a saline-mannitol solution. GI transit time of PEG and absorption of
      radiolabeled bile acid were measured simultaneously while subjects ingested three
      meals per day. To obtain a diarrhea control group for transit time and bile acid
      absorption, normal subjects were studied when they had diarrhea caused by
      ingestion of Milk of Magnesia (MOM). RESULTS: Diarrhea could not be explained by
      malabsorption of ingested nutrients, bacterial overgrowth, bile acid
      malabsorption, or epithelial cell malabsorption of electrolytes. However, 25% of
      polyethylene glycol (PEG) ingested with a standard meal was recovered in stool in
      45 min, which is 10 times faster than in normal subjects with equally severe
      diarrhea caused by ingestion of MOM. All of the patients had autonomic neuropathy
      that remained unrecognized for 15-36 months after onset of chronic diarrhea; it
      seems likely that this was the cause of rapid transit. CONCLUSIONS: Severe
      chronic diarrhea in three patients with systemic amyloidosis was mediated by
      extremely rapid transit of chyme and digestive secretions through the intestine.

PMID- 14572572
TI  - Anti-Saccharomyces cerevisiae antibodies: a stable marker for Crohn's disease
      during steroid and 5-aminosalicylic acid treatment.
AB  - OBJECTIVES: An increased prevalence of elevated serum anti-Saccharomyces
      cerevisiae antibody (ASCA) levels in patients with Crohn's disease (CD) has been
      described. The aim of the present work was to investigate serum ASCA levels
      during the courses of prednisolone and mesalamine therapy in CD patients.
      METHODS: Serum samples of 25 patients with active CD were studied for ASCA levels
      before as well as 2 and 9 wk after initiation of a prednisolone tapering regimen.
      The influence of mesalamine (4 g o.d.) on serum ASCA levels compared to that of
      placebo was tested over 1 yr in 38 patients (20 mesalamine and 18 placebo)
      participating in a postoperative prophylaxis study. Serum IgG and IgA ASCA levels
      were measured by ELISA. Sera of 91 CD and 40 ulcerative colitis (UC) patients as
      well as 334 healthy donors were tested for ASCA to recalculate new cut-off
      values. RESULTS: For IgG ASCA cut-off values were determined to be 17.0 U and
      25.0 U, and for IgA ASCA 9.3 U and 14.0 U. At baseline visit, 73.0% (46/63) of
      patients displayed serum ASCA positivity. During prednisolone therapy, a decrease
      in serum IgG and IgA ASCA levels from baseline to wk 2 (p < 0.0001 and p < 0.001,
      respectively) as well as to wk 9 (p < 0.001 and p = 0.01, respectively) was
      observed. A trend toward an association of ASCA positivity and steroid
      responsiveness was calculated (p = 0.07). During mesalamine treatment, no
      differences in changes of ASCA levels were observed compared to placebo at any
      time point. CONCLUSIONS: ASCA are stable markers during steroid and mesalamine
      treatment, highlighting their reliability for use in diagnosis of CD.

PMID- 14572573
TI  - The effects of infliximab maintenance therapy on health-related quality of life.
AB  - OBJECTIVES: The ACCENT I study evaluated the long term effects of infliximab as
      maintenance therapy for patients with Crohn's disease. Health-related quality of
      life (HRQL) was also assessed in the trial. METHODS: In ACCENT I, a total of 573
      patients received a single infusion of 5 mg/kg infliximab at baseline. After
      assessment of response at wk 2, patients were randomly assigned repeat infusions
      of placebo at wk 2 and 6 and then every 8 wk thereafter until wk 46 (single
      dose), repeat infusions of 5 mg/kg of infliximab at the same time points (5 mg/kg
      maintenance), or 5 mg/kg of infliximab at wk 2 and 6 followed by 10 mg/kg (10
      mg/kg maintenance). HRQL analyses presented include the 335 patients classified
      as wk-2 responders. The treatment regimens were compared with regard to their
      change from baseline in the IBDQ and Short Form-36 (SF-36) scores. RESULTS:
      Baseline scores indicated substantial impairment in HRQL. Throughout the study,
      all IBDQ and SF-36 scores were improved at all time points compared to baseline.
      After wk 10 and through wk 54, these improvements were greater in the two
      infliximab maintenance groups than in the single-dose group. The mean change from
      baseline to wk 54 in total IBDQ was greater in the 5-mg/kg maintenance group
      (22.1, p < 0.05) and 10-mg/kg maintenance group (30.2, p < 0.001) than in the
      single-dose group (8.9). Similarly, the mean change from baseline to wk 54 in the
      PCS of the SF-36 was greater in the 5-mg/kg maintenance group (6.1, p < 0.05) and
      10-mg/kg maintenance group (7.2, p < 0.01) than in the single-dose group (2.5).
      CONCLUSIONS: Infliximab therapy provides substantially improved HRQL as measured
      by both the disease-specific IBDQ and the generic SF-36. A maintenance regimen of
      either 5 mg/kg or 10 mg/kg of infliximab is more effective than a single 5-mg/kg
      infliximab infusion in sustaining this benefit.

PMID- 14572574
TI  - Management of Crohn's disease of the ileoanal pouch with infliximab.
AB  - OBJECTIVES: The occurrence of Crohn's disease (CD) in a patient with an ileal
      pouch anastomosis (IPAA) often results in severe morbidity and significant chance
      of reservoir loss. We report our experience of the use of infliximab in these
      patients. METHODS: Medical records of 26 patients with an IPAA and CD-related
      complications were reviewed. The median time between the IPAA and the diagnosis
      of CD was 4.5 yr (range 0.1-16 yr). The main reasons for changing the original
      ulcerative colitis diagnosis to CD were complex perianal or pouch fistulizing
      disease in 14 patients (54%), prepouch ileitis in five (19%), and both prepouch
      ileitis and complex fistula in seven (27%). Patients received one to three doses
      of infliximab over 8 wk as induction therapy. Subsequently the patients received
      a variable number of maintenance infusions. RESULTS: At a short term follow-up,
      16/26 patients (62%) had a complete response, six of 26 (23%) had a partial
      response, and four of 26 (15%) had no response. Information regarding long term
      follow-up was available in 24 patients. After a median follow-up of 21.5 months
      (range 3-44 months), eight patients (33%) either had their pouch resected or had
      a persistent diverting ileostomy. The pouch was functional in 16/24 (67%)
      patients, with either good (n = 7) or acceptable (n = 7) clinical results in
      14/24 (58%). Of those 14 patients, 11 were under long term, on demand, or
      systematic maintenance treatment with infliximab. CONCLUSIONS: Infliximab is
      beneficial in both the short and long term treatment of patients with an IPAA
      performed for a presumed diagnosis of ulcerative colitis who subsequently develop
      CD-related complications. Good pouch function requires long term treatment with
      infliximab in most patients.

PMID- 14572575
TI  - Lactulose/mannitol test has high efficacy for excluding organic causes of chronic
      diarrhea.
AB  - OBJECTIVES: Diagnosis in chronic diarrhea in the absence of a distinctive
      clinical pattern is often challenging, as biochemical tests prescribed at the
      first evaluation do not show enough sensitivity and specificity to tailor further
      investigation. Intestinal permeability to sugars is an accurate test for
      detecting intestinal damage. The aim of this study was to evaluate the diagnostic
      value of the lactulose/mannitol (L/M) test in patients with chronic diarrhea.
      METHODS: We conducted a prospective cohort study to evaluate the diagnostic value
      of the L/M test in chronic diarrhea. The test was administered to 261 consecutive
      patients presenting with three or more bowel movements daily for at least 3 wk.
      Biochemical tests including complete blood cell count, acute phase reactive
      proteins, serum albumin and iron, and stool cultures for bacteria, ova, and
      parasites were assessed at the same time. Additional diagnostic investigations
      were directed by clinical features as well as first-line test results. RESULTS:
      Over 3 yr, 120 (46%) of our patients were found to have an organic cause for
      chronic diarrhea, whereas in 141 (54%) a functional condition was diagnosed.
      Multivariate logistic regression analysis revealed that the L/M test and C
      reactive protein were independent predictors for the final diagnosis of organic
      cause of chronic diarrhea, with odds ratios of 1.5 (95% CI = 1.29-1.78) and 5.2
      (95% CI = 1.90-14.12), respectively. The area under the receiver operating
      characteristic (ROC) curve of the adjusted model was 0.82, with positive
      predictive value of 80.4% and negative predictive value of 77.7%. CONCLUSIONS:
      The L/M test is a powerful tool for workup in patients with chronic diarrhea.
      Introducing the L/M test as first-level test effectively improves the selection
      of patients who need further evaluation.

PMID- 14572576
TI  - Stimulation of the nitric oxide-guanosine 3', 5'-cyclic monophosphate pathway by
      sildenafil: effect on rectal muscle tone, distensibility, and perception in
      health and in irritable bowel syndrome.
AB  - OBJECTIVES: Nitric oxide, a neurotransmitter in the noncholinergic, nonadrenergic
      nervous system, is a mediator of relaxation of GI smooth muscle and of visceral
      nociception mainly studied in vitro. Sildenafil stimulates the nitric oxide
      guanosine 3', 5'-cyclic monophosphate (NO-cGMP) pathway through inhibition of
      phosphodiesterase 5. The aims of this study were to evaluate in vivo the effect
      of stimulation of the NO-cGMP pathway on rectal tone, distensibility, and
      perception in healthy individuals and in patients with irritable bowel syndrome
      (IBS). METHODS: In eight healthy subjects and four patients with IBS rectal tone,
      distensibility and perception thresholds were measured with an electronic
      barostat both before and 60 min after administration of sildenafil (50 mg p.o.).
      Perception was scored on a graded scale of 0-6. At the end of a distension series
      an anatomic questionnaire was filled out by the subjects. RESULTS: Sildenafil
      significantly reduced rectal tone in healthy subjects (intrabag volume predrug:
      145.5 +/- 18.7 ml vs postdrug: 164.4 +/- 16.9 ml, p = 0.01) and IBS (111.3 +/-
      25.2 ml vs 136.5 +/- 33.3 ml; p = 0.01) but did not alter rectal compliance
      (healthy subjects: 5.8 +/- 0.4 vs 6.3 +/- 0.6 ml/mm Hg, p > 0.05; IBS subjects:
      6.1 +/- 0.6 vs 7.1 +/- 1.0 ml/mm Hg, p > 0.05). Intrabag pressure and rectal wall
      tension to reach perception thresholds for initial sensation, sensation of stool,
      and urgency were not altered by sildenafil. However, intrabag volumes to reach
      these thresholds were significantly increased by sildenafil both in healthy
      subjects and in patients with IBS. Viscerosomatic referral was unchanged.
      CONCLUSIONS: Stimulation of the NO-cGMP pathway decreases rectal tone but does
      not influence rectal distensibility. Relaxation of the rectum is accompanied by
      an increase in rectal volumes to reach perception thresholds in healthy subjects
      and in patients with IBS, but no direct effect on rectal perception can be
      demonstrated.

PMID- 14572577
TI  - Significance of hepatitis B viremia levels determined by a quantitative
      polymerase chain reaction assay in patients with hepatitis B e antigen-negative
      chronic hepatitis B virus infection.
AB  - OBJECTIVES: In hepatitis B e antigen (HBeAg)-negative chronic hepatitis B virus
      (HBV) infection, the clinical relevance of low viremia levels remains unclear. We
      evaluated the clinical significance of a single baseline serum HBV DNA
      measurement by a quantitative polymerase chain reaction (PCR) assay in this
      setting. METHODS: In total, 196 patients with HBeAg-negative chronic HBV
      infection (62 inactive carriers, 134 with chronic hepatitis B) were studied. ALT
      activity was normal at baseline in 25/134 HBeAg-negative chronic hepatitis B
      patients (18.7%), whereas it remained normal throughout follow-up in all inactive
      carriers. RESULTS: HBV DNA was <30,000 copies/ml in 14 (10.5%) and <100,000
      copies/ml in 17 (12.9%) HBeAg-negative chronic hepatitis B patients, whereas it
      was <30,000 copies/ml in all inactive carriers (undetectable in 14). In
      particular, HBV DNA levels were <100,000 copies/ml in eight (32%) and <30,000
      copies/ml in five (20%) of the 25 patients with HBeAg-negative chronic hepatitis
      B and normal baseline ALT values. HBV DNA levels with a cut-off at 30,000 or
      100,000 copies/ml could correctly classify 92.9% or 91.3% of patients with HBeAg
      negative chronic HBV infection, whereas ALT or IgM anti-HBc (IgM class antibody
      to HBV core antigen) index > 0.200 could correctly classify only 87.2% and 82.1%
      of patients, respectively. A combined HBV DNA and IgM anti-HBc index performed
      better by correctly classifying 94.4% of cases. CONCLUSIONS: Serum HBV DNA levels
      evaluated by sensitive quantitative PCR assays can be used for differentiation
      between HBeAg-negative chronic hepatitis B and inactive hepatitis B surface
      antigen carrier state, but the cut-off level should be set at approximately
      30,000 copies/ml and certainly lower than the recently suggested level of 100,000
      copies/ml.

PMID- 14572578
TI  - Alendronate is more effective than etidronate for increasing bone mass in
      osteopenic patients with primary biliary cirrhosis.
AB  - OBJECTIVES: Osteopenia increases the morbidity of primary biliary cirrhosis
      (PBC). In this study, we have compared two bisphosphonates, alendronate and
      cyclical etidronate, that inhibit osteoclast-mediated bone resorption and have
      examined their effects on bone mass in patients with this disease. METHODS: A
      total of 32 women with PBC were randomly assigned to receive alendronate (10
      mg/day) or etidronate (400 mg/day) for 14 days every 3 months. Bone mineral
      density of the lumbar spine and proximal femur were measured initially and every
      6 months. Bone fractures and markers of bone mineral metabolism were also
      evaluated. RESULTS: Sixteen patients were allocated to each group, which were
      comparable with respect to the severity of PBC and osteopenia. Thirteen patients
      in each group completed the 2-yr trial. Both treatments increased bone mineral
      density after 2 yr, although the increase at the lumbar spine and at the proximal
      femur was significantly higher in patients receiving alendronate than in patients
      on etidronate. This higher effect of alendronate paralleled with changes in the
      biochemical markers of bone turnover. No patient developed new vertebral
      fractures, but new peripheral fractures were detected in two patients on
      alendronate and in one on etidronate. There were no serious adverse effects.
      Neither treatment impaired liver function or cholestasis. CONCLUSIONS:
      Alendronate effectively increases bone mass and has greater antiresorptive power
      than etidronate in patients with primary biliary cirrhosis, and is associated
      with minor or no side effects.

PMID- 14572579
TI  - Origin of oxysterols in hepatic bile of patients with biliary infection.
AB  - OBJECTIVES: Oxysterols are ubiquitous in the body and are potential cytotoxic
      agents in addition to being metabolic regulators. Although bile contains high
      concentrations of cholesterol, oxysterol concentrations in bile and the effect of
      infection on oxysterol levels have not been measured, nor has their origin been
      studied. The purpose of this study was to determine if infection of the biliary
      tract was associated with increased concentrations of oxysterols in the bile and,
      if so, which oxysterols showed a significant change. METHODS: Hepatic bile was
      obtained from eight patients with biliary tract disease by means of a naso
      biliary catheter. Oxysterols were extracted and purified by solid-phase
      extraction, derivatized and measured by gas chromatography-mass spectrometry.
      RESULTS: The following were quantified in hepatic bile: 7-alpha
      hydroxycholesterol, 7-beta-hydroxycholesterol, cholestan-3-beta,5-alpha,6-beta
      triol, 25-hydroxycholesterol, 26-hydroxycholesterol, 7-ketocholesterol, and 7
      alpha-hydroxy-4-cholesten-3-one. Total oxysterols in hepatic bile ranged from
      0.133 mumol/L to 7.748 mumol/L (1.47 +/- 2.55 mumol/L). Levels of 7-alpha
      hydroxycholesterol and 7-beta-hydroxycholesterol were increased in infected bile
      (14.2 +/- 15.1 x 10(-3)% of cholesterol vs 1.9 +/- 0.5 x 10(-3)% of cholesterol,
      p < 0.05, and 22.0 +/- 25.0 x 10(-3)% of cholesterol vs 1.6 +/- 1.2 x 10(-3)% of
      cholesterol, p < 0.05, respectively). Serum C-reactive protein levels correlated
      positively with biliary levels of 7-alpha-hydroxycholesterol (R = 0.948), 7-beta
      hydroxycholesterol (R = 0.976), cholestan-3-beta,5-alpha,6-beta-triol (R =
      0.823), 7-alpha-hydroxy-4-cholesten-3-one (R = 0.846,) and 7-ketocholesterol (R =
      0.973). Different oxysterols were found in gallstones, chiefly 3-keto-cholest-4
      ene (624 +/- 316 parts per million [ppm] of dry weight), 3-keto-cholesta-4,6
      diene (240 +/- 329 ppm) and 7-keto-cholesterol (77 +/- 81 ppm). Incubation of
      human leukocytes with model bile in the presence of bacterial lipopolysaccharide
      resulted in changes in sterol composition, including increases in oxysterols. We
      have identified and quantified oxysterols from uninfected and infected human
      hepatic bile and from gallstones and gallbladder bile. Biliary infection may be
      involved in the biogenesis of oxysterols in bile through the production of
      reactive oxygen species from activated leukocytes.

PMID- 14572580
TI  - Response to treatment of hepatitis C in individuals with a recent history of
      intravenous drug abuse.
AB  - OBJECTIVE: The aim of this study was to determine the rate of sustained response
      (SR) to high-dose daily interferon (IFN) therapy in prior drug abusers with
      chronic hepatitis C. This was a retrospective matched cohort study conducted at a
      tertiary care university hospital in a large urban area. METHODS: The 120
      individuals in each cohort were treated by the same physicians at the same
      facility, using the same treatment protocol and management procedures. Each
      patient received 5 million units of IFN daily for at least 1 yr and usually
      longer. RESULTS: Both groups achieved a similar rate of SR (no i.v. drug abuse,
      37% vs i.v. drug abuse, 33%). The end of treatment (ET) response rate was
      unexpectedly higher in the drug-abusing population as compared to that non-drug
      abusing control subjects but fell during the follow-up period to achieve an SR
      similar to that of the non-drug-abusing controls. The side effects of IFN therapy
      were no greater in the prior drug abusing population than in the controls,
      although many in the drug-abusing group increased their dose of methadone to
      counteract IFN side effects. CONCLUSIONS: The SR rate achieved by intravenous
      drug abusers to high-dose, daily IFN is similar to that in a non-drug-abusing HCV
      positive population. Recent use of illicit drugs within a 6-month period of
      starting IFN therapy or continued methadone use during treatment does not seem to
      impair the response to IFN when the results are compared with those of a matched
      cohort of non-drug-abusing controls.

PMID- 14572581
TI  - Hepatitis B vaccine nonresponse and celiac disease.
AB  - OBJECTIVES: There is a genetic predisposition to hepatitis B vaccine nonresponse.
      The link between human leukocyte antigen (HLA) genotype and ineffective
      development of immunity to the hepatitis B vaccine has been characterized in
      multiple studies. Celiac disease has a strong association with a particular HLA
      genotype of DQ2; interestingly, this HLA genotype is seen in association with
      nonresponders to the hepatitis B vaccine. We report a disproportionate number of
      patients with celiac disease who are nonresponders to the hepatitis B vaccine
      series. METHODS: We reviewed the hepatitis B vaccine records, serological tests
      for anti-hepatitis B surface antigen antibody (anti-HBs), and HLA genotypes of
      celiac disease patients identified as nonresponders to hepatitis B vaccine.
      Subjects were identified from a database of patients diagnosed with celiac
      disease at our institution or referred to our center for evaluation and
      management of celiac disease between November, 2000, and October, 2002. RESULTS:
      A total of 23 subjects were reviewed. All had a clinical and pathological
      diagnosis of celiac disease. All subjects reported receiving the full series of
      hepatitis B vaccinations. Of the subjects, 19 had testing for hepatitis B vaccine
      response. Of these 19 subjects, 13 did not achieve long-term immunity as seen by
      the negative qualitative or quantitative anti-HBs antibody titer. All tested
      subjects were either homozygous or heterozygous for DQ2. CONCLUSIONS: We
      postulate that celiac disease patients may have a significant predisposition to
      hepatitis B vaccine nonresponse. Both celiac disease and hepatitis B vaccine
      nonresponse is genetically mediated. Celiac disease patients may have a failure
      of induction of humoral immune response needed for development of long term
      immunity; the mechanism for this is unclear.

PMID- 14572582
TI  - Diabetes mellitus is a risk factor for hepatic decompensation in patients with
      hepatocellular carcinoma undergoing resection: a longitudinal study.
AB  - OBJECTIVES: Patients with hepatocellular carcinoma (HCC) frequently have diabetes
      mellitus (DM) due to coexisting liver cirrhosis. The aim of this study was to
      assess the long-term impact of DM on the hepatic regenerative ability of HCC
      patients undergoing surgical resection. METHODS: We retrospectively studied 245
      HCC patients (210 male; age, 61 +/- 13 yr) with well-preserved liver functions
      undergoing resection. Forty (16%) of them were diabetic and were controlled with
      hypoglycemic agents. The Child-Pugh scoring system was used to evaluate the
      postoperative liver regeneration ability. The endpoint was the occurrence of
      hepatic decompensation, defined as a sustained increase in the Child-Pugh score
      of 2 or more points or the development of tumor recurrence. RESULTS: Seventy-five
      patients (31%) developed hepatic decompensation during a follow-up period of 27
      +/- 18 months (range, 3-75). DM (p = 0.001), large (>3 cm) tumor size (p =
      0.044), and age > 65 yr (p = 0.058) were the factors associated with hepatic
      decompensation in univariate analysis. Multivariate Cox regression model analysis
      confirmed that DM (relative risk [RR] = 2.3, 95% CI = 1.4-3.7, p = 0.001) and
      tumor size > 3 cm (RR = 1.7, 95% CI = 1.1-2.7, p = 0.046) were independent
      prognostic predictors associated with the occurrence of hepatic decompensation;
      the respective 3- and 5-yr cumulative rates were 53% and 64% versus 27% and 50%
      for diabetic and nondiabetic patients, and 24% and 41% versus 38% and 60% for
      patients with small (< or =3 cm) versus large (>3 cm) tumors. CONCLUSION: HCC
      patients with DM or large tumor size are at a cumulative increased risk for
      postoperative hepatic decompensation.

PMID- 14572584
TI  - Hyperplastic polyps in hereditary nonpolyposis colorectal cancer.
AB  - OBJECTIVES: Hereditary nonpolyposis colorectal cancer (HNPCC) is a genetic
      syndrome caused by germline mutations in DNA mismatch repair (MMR) genes, in
      particular hMLH1, hMSH2, and hMSH6. Dysfunction of MMR genes leads to loss of MMR
      protein expression and to microsatellite instability (MSI). MSI is also detected
      in 10-20% of sporadic colorectal cancers. Hyperplastic polyps (HP) may serve as
      precursor for these MSI+ sporadic colorectal cancers. The aim of this study was
      to examine whether hyperplastic polyps are also possible premalignant lesions in
      HNPCC. METHODS: All HPs resected from (suspected) mismatch repair gene mutation
      carriers were retrieved from a screening program database. Clinical information
      on patient age at colonoscopy and location of the HP was collected. MLH1, MSH2,
      and MLH6 protein expression was evaluated using immunohistochemistry. RESULTS: A
      total of 90 HPs were resected from 21 men and 19 women. The mean patient age at
      resection was 45.7 yr (44.7 yr in men and 46.6 yr in women). In all patients, 19
      (21%) HPs were resected from the proximal colon, 23 (26%) from the distal colon,
      and 48 (53%) from the rectum. None of the HPs demonstrated loss of MMR protein
      expression. CONCLUSIONS: Mismatch repair dysfunction in HPs of HNPCC patients is
      apparently very rare. It seems unlikely that HPs in HNPCC patients are precursors
      for (MSI+) cancers in these patients.

PMID- 14572583
TI  - Prospective evaluation of fecal calprotectin as a screening biomarker for
      colorectal neoplasia.
AB  - OBJECTIVES: Stool testing is a well established method of screening for
      colorectal neoplasia. Emerging data suggest that novel biomarkers may offer
      performance advantages over fecal occult blood. In this large, prospective study,
      we assessed fecal calprotectin (a leukocyte-derived protein) as a screening
      biomarker for colorectal neoplasia. Fecal calprotectin was directly compared to
      fecal hemoglobin (Hb) and colonoscopy as the existing criterion standards for
      stool screening and structural evaluation, respectively. METHODS: Subjects
      included colonoscopy patients with a personal history of colorectal neoplasia,
      family history of colorectal cancer, or iron deficiency anemia. Stool specimens
      were collected before purgation, processed appropriately, and quantitatively
      analyzed for calprotectin (Nycomed Pharma, Oslo, Norway) and for Hb (Mayo Medical
      Laboratories, Rochester, MN) by masked technicians. Colonoscopies were performed
      by experienced endoscopists without prior knowledge of the fecal assay results.
      RESULTS: Among 412 subjects, 97 (24%) subjects had one or more colorectal
      neoplasms (including three with adenocarcinomas). Fecal calprotectin levels did
      not differ significantly between subjects with versus subjects without colorectal
      neoplasms (p = 0.33). Neither tumor number (p = 0.85) nor tumor size (p = 0.86)
      significantly influenced the observed fecal calprotectin concentrations.
      Estimates of the sensitivity, specificity, and positive and negative predictive
      values of fecal calprotectin for any colorectal neoplasms were 37%, 63%, 23%, and
      76%, respectively. Comparable performance estimates for fecal Hb were 3%, 97%,
      27%, and 77%, respectively. CONCLUSIONS: In this cohort of colonoscopy patients
      at above average risk, fecal calprotectin was a poor screening biomarker for
      colorectal neoplasia. Further investigation of tumor-derived, rather than blood
      based, biomarkers may be a more rewarding approach to stool screening for
      colorectal neoplasia.

PMID- 14572586
TI  - A prospective study of the clinical, genetic, screening, and pathologic features
      of a family with hereditary mixed polyposis syndrome.
AB  - In 1997, hereditary mixed polyposis syndrome (HMPS) was described in an Ashkenazi
      pedigree having colorectal polyps with mixed histology and risk for colorectal
      cancer (CRC). The mutation is now localized to 15q13-14. Since 1980, compliant
      relatives of an HMPS family were seen annually, tested genetically, and had
      colonoscopy offered every 1 to 2 yr from age 20 yr. The Israeli pedigree has 37
      members (17 clinically affected by CRC or polyps), and seven of 13 available
      relatives entered our screening program. The others, followed-up elsewhere,
      provided clinical information. Half of our screened group had rectal bleeding;
      others were asymptomatic. Colonoscopy, performed a mean of four times, identified
      polyps in all seven patients (mean age 28 yr). Polyps were removed and included
      juvenile adenomas, mixed juvenile adenomas, hyperplastic polyps, mixed
      hyperplastic adenomas, serrated adenomas, and tubular adenomas. None of our
      screened patients developed CRC or extracolonic neoplasia. Linkage analysis
      localized their mutation to 15q13-14. This high-penetrance founder mutation so
      far is described only in Ashkenazim. The CRC pathway seems to be through juvenile
      and hyperplastic polyps. Mutation identification will aid screening for and
      evaluation of HMPS prevalence in Jewish and non-Jewish populations. Meanwhile, a
      cancer pedigree and correct classification of polyps will identify HMPS families.
      They require early and frequent colonoscopy, polypectomy, and elective extensive
      colectomy when indicated.

PMID- 14572585
TI  - Prevalence of advanced neoplasia at screening colonoscopy in men in private
      practice versus academic and Veterans Affairs medical centers.
AB  - OBJECTIVES: Several large population studies assessing the yield of average risk
      screening colonoscopy have evaluated Veterans Affairs (VA) populations. It
      remains uncertain how generalizable these findings are to men in the general
      population. The aim of this study was to define the prevalence of advanced
      neoplasia in male patients undergoing screening colonoscopy in diverse practice
      settings. METHODS: The Clinical Outcomes Research Initiative (CORI) national
      endoscopic database was analyzed to compare the findings in men undergoing
      average risk screening colonoscopy in community, academic, and VA endoscopy
      settings. RESULTS: Between January, 1998, and May, 2002, a total of 9109 men
      underwent screening colonoscopy in community (5625), academic (2269), and VA
      (1215) settings. Overall yield of colonic lesions (mass or polyp >9 mm) on
      average risk colonoscopy was 5.1%; 5.7% (community), 3.4% (academic), and 5.9%
      (VA) in each site, respectively. Among patients with lesions identified, multiple
      lesions >9 mm were less common in academic settings (6.4%) compared to community
      (12.0%) or VA (8.9%) sites. When adjusting for age and ethnicity on multivariate
      analysis, colonic lesion detection at VA sites was similar to community settings.
      However, lesion identification was more likely in both settings (VA: OR = 1.72;
      community: OR = 1.56) compared to academic centers. CONCLUSIONS: Age- and race
      adjusted prevalence of polyps >9 mm in men who receive screening colonoscopy was
      significantly lower in academic sites compared to VA and community practice
      sites. One must be cautious in generalizing the findings of male patient studies
      from academic centers to the entire population.

PMID- 14572587
TI  - Fibrin glue for anal fistulas.

PMID- 14572588
TI  - Endoscopic GERD therapy: is enteryx the answer?

PMID- 14572589
TI  - What does sigmoidoscopy really miss?

PMID- 14572590
TI  - Re: Balaban et al.--Low volume bowel preparation for colonoscopy: randomized
      endoscopist-blinded trial of liquid sodium phosphate versus tablet sodium
      phosphate.

PMID- 14572592
TI  - Nonalcoholic steatohepatitis: role of leptin in pathogenesis and benefits of
      metformin in treatment.

PMID- 14572594
TI  - Re: Tham et al.--Safety of ERCP during pregnancy.

PMID- 14572596
TI  - Re: Gomez-Cerezo et al.--Pancreatic ascites: study of therapeutic options by
      analysis of case reports and case series between the years 1975 and 2000.

PMID- 14572598
TI  - Avoiding infliximab in the treatment of Crohn's disease in patients with multiple
      sclerosis.

PMID- 14572600
TI  - Hepatic mitochondrial beta-oxidation in patients with nonalcoholic
      steatohepatitis assessed by 13C-octanoate breath test.

PMID- 14572599
TI  - "Green juice"-associated granulomatous hepatitis.

PMID- 14572601
TI  - Chronic viral hepatitis, interferon, diabetes mellitus, and celiac disease.

PMID- 14572603
TI  - Arachidonic acid cascade inhibitors modulate phorbol ester-induced oxidative
      stress in female ICR mouse skin: differential roles of 5-lipoxygenase and
      cyclooxygenase-2 in leukocyte infiltration and activation.
AB  - We recently developed a short-term assay for skin H2O2 generation induced by
      double 12-O-tetradecanoylphorbol-13-acetate (TPA) applications for mechanistic
      study on skin epidermal carcinogenesis. In the present study, we investigated the
      individual roles of arachidonic acid metabolism in H2O2 generation in mouse skin
      inflammation. The experiments using inhibitors of arachidonic acid (AA)
      metabolism showed that corticosteroid and a lipoxygenase (LO) inhibitor
      expectedly suppressed double TPA application-induced H2O2 generation through the
      interference of chemotactic action but not by direct decomposition or scavenging.
      We also demonstrated that the treatment of AA (1 mumol) and 5-LO metabolites
      including leukotriene B4 (LTB4) partly mimicked, though soybean LO-derived lipid
      hydroperoxide and prostaglandins did not, the priming effect evaluated by edema
      formation and leukocyte infiltration. We also confirmed that inflammatory
      leukocytes accumulated by LTB4 generated a significant amount of H2O2 by TPA
      stimulation. These results suggested that 5-LO metabolites of AA are the
      potential key molecules in the TPA-induced priming event. Interestingly, the
      cyclooxygenase (COX-) 2-selective inhibitor nimesulide (NS) and celecoxib (CXB)
      showed different responses than those of other inhibitors. These agents showed no
      specific potential to inhibit the priming event but significantly suppressed H2O2
      generation, lipid peroxidation, and hyperplasia in mouse skin. From the results
      based on an in vitro leukocyte differentiation model, we speculated that the
      antioxidant effect of the COX-2 inhibitors might be partly associated with both
      counteraction of proinflammatory cytokine-enhanced ROS generation and inhibition
      of CD11b, an important molecule for cell adhesion, expression. Indeed, the
      topical application of NS attenuated the number of infiltrated leukocytes induced
      by TPA in mouse skin. Thus, these gathered data indicated the differential roles
      of 5-LO and COX-2 in leukocyte adhesion, infiltration, and H2O2 generation.

PMID- 14572604
TI  - The metabolism of sulindac enhances its scavenging activity against reactive
      oxygen and nitrogen species.
AB  - Sulindac is a sulfoxide prodrug that, in vivo, is converted to the metabolites
      sulindac sulfide and sulindac sulfone. It is therapeutically used as an anti
      inflammatory and analgesic in the symptomatic treatment of acute and chronic
      rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis. In addition to
      its anti-inflammatory properties, sulindac and its metabolites have been shown to
      have an important role in the prevention of colonic carcinogenesis. Although the
      inhibition of prostaglandin synthesis constitutes the primary mechanism of action
      of sulindac, it is well known that reactive oxygen species (ROS) and reactive
      nitrogen species (RNS) are implicated in the pathophysiology of inflammation and
      cancer. Thus, the aim of this study was to evaluate the scavenging activity of
      sulindac and its sulfone and sulfide metabolites for an array of ROS (HO*, O2(*
      ), and HOCl) and RNS (*NO and ONOO-) using in vitro systems. The results we
      obtained demonstrate that the metabolism of sulindac increases its scavenging
      activity for all RNS and ROS studied, notably with regard to the scavenging of
      HOCl. These effects may strongly contribute to the anti-inflammatory and
      anticarcinogenic efficacy that has been shown for sulindac.

PMID- 14572605
TI  - Selenium-containing compounds attenuate peroxynitrite-mediated NF-kappaB and AP-1
      activation and interleukin-8 gene and protein expression in human leukocytes.
AB  - A growing body of evidence indicates that the powerful oxidant peroxynitrite
      (ONOO(-)) may function as an intracellular signal for production of
      proinflammatory cytokines, such as interleukin-8 (IL-8) in human leukocytes. In
      this study, we investigated whether selenomethionine, selenocysteine, and the
      synthetic organoselenium compound ebselen (2-phenyl-1,2-benzisoselenazol-3(2h)
      one) could inhibit ONOO(-)-mediated IL-8 gene expression in human leukocytes in
      whole blood. At micromolar concentrations, ebselen, selenomethionine, and
      selenocysteine effectively prevented nuclear accumulation of activator protein-1
      (AP-1) and nuclear factor kappaB (NF-kappaB) evoked by exogenous ONOO(-), in both
      polymorphonuclear and mononuclear leukocytes, and inhibited IL-8 gene and protein
      expression. The inhibitory actions of selenium-containing molecules were
      concentration-dependent (EC(50) values: 8.0-13.2 muM) and were not shared by
      their sulphur analogs methionine and cystine. Furthermore, ebselen,
      selenomethionine, and selenocysteine markedly reduced LPS-evoked intracellular
      ONOO(-) formation in leukocytes, resulting in 36-66% decreases in nuclear
      accumulation of AP-1 and NF-kappaB in both polymorphonuclear and mononuclear
      leukocytes and inhibition of IL-8 mRNA expression and IL-8 release. These
      findings indicate that selenium-containing compounds can effectively oppose ONOO(
      ) signaling in leukocytes and suggest a role for selenium-containing molecules as
      potential modifiers of inappropriate leukocyte trafficking under pathological
      conditions associated with enhanced ONOO(-) formation.

PMID- 14572606
TI  - The role of antioxidant enzymes in TCDD-induced oxidative stress in various brain
      regions of rats after subchronic exposure.
AB  - The induction of oxidative stress by TCDD in various brain regions of rats has
      been investigated after subchronic exposure. TCDD was administered by gavage to
      female Sprague-Dawley rats at daily doses of 0, 10, 22, and 46 ng/kg for 13
      weeks. The brains were dissected to cerebral cortex (Cc), hippocampus (H),
      cerebellum (C), and brain stem (Bs); the production of superoxide anion (SA) and
      lipid peroxides and the activities of the antioxidant enzymes superoxide
      dismutase (SOD), catalase, and glutathione peroxidase (GSH-Px) were determined in
      those regions. TCDD caused dose-dependent increases in the production of SA and
      lipid peroxidation in Cc and H and those were associated with dose-dependent
      suppressions of SOD. While a TCDD dose of 10 ng/kg/d resulted in significant
      increases in catalase and GSH-Px activities in Cc and H, doses of 22 and 46
      ng/kg/d resulted in dose-dependent suppressions of these two enzymes in the same
      regions. In the C and Bs, TCDD treatment did not result in significant production
      of SA and lipid peroxidation but it resulted in dose-dependent increases in the
      activities of various antioxidant enzymes. These results suggest that Cc and H
      are vulnerable to TCDD-induced oxidative stress after subchronic exposure, and
      that C and Bs are protected against that effect.

PMID- 14572607
TI  - Rho A negatively regulates cytokine-mediated inducible nitric oxide synthase
      expression in brain-derived transformed cell lines: negative regulation of
      IKKalpha.
AB  - The present study describes the role of RhoA as a negative regulator of iNOS
      expression via the inactivation of NF-kappaB in transformed brain cell lines
      [C(6) glioma, human astrocytoma (T98G, A172), neuroblastoma (NEB), and immortal
      rat astrocytes]. Treatment with lovastatin resulted in the induction of LPS/IFN
      gamma-mediated iNOS mRNA and increased nitric oxide (NO) production. The addition
      of mevalonate and geranylgeranylpyrophosphate (GGPP) reversed the lovastatin
      mediated effect, whereas FPP had no effect. An inhibitor of
      geranylgeranyltransferase inhibitor (GGTI 298) further induced the cytokine and
      lovastatin-mediated iNOS expression, suggesting the involvement of
      geranylgeranylated proteins in the regulation of iNOS. Bacterial toxin B
      (inactivates RhoA, B, and C; CDC42; Rac proteins), C3 ADP-ribosyltransferase (C3)
      toxin from C. botulinum (inactivates RhoA, B, and C proteins), and Y-27632
      (selective inhibitor of Rho-associated kinases) increased the LPS/IFN-gamma
      mediated iNOS expression. Lovastatin treatment induced NO by increasing NF-kappaB
      translocation and its association with the CREB-binding protein (CBP/p300) via
      the downregulation of RhoA. Inhibition of RhoA resulted in increased activation
      of IKKalpha. Cotransfection studies with dominant-negative form of RhoA and iNOS
      luciferase or NF-kappaB-luciferase reporter constructs further support these
      observations. Taken together, these studies show that downregulation of RhoA by
      lovastatin resulted in increased iNOS expression via the activation of NF-kappaB
      CBP/p300 pathway in transformed brain cells.

PMID- 14572608
TI  - Akt activation induced by an antioxidant compound during ischemia-reperfusion.
AB  - Molecular mechanisms of cardioprotection afforded by modified mexiletine
      compounds were investigated during ischemia-reperfusion (IR) in Langendorff
      perfused hearts. Rat hearts were subjected to a global 25 min ischemia followed
      by reperfusion, either untreated or treated with mexiletine, or three substituted
      mexiletine derivates (5 muM). A modified mexiletine derivative (H-2693) promoted
      best the recovery of myocardial energy metabolism (assessed by (31)P NMR
      spectroscopy) compared to untreated and mexiletine-treated hearts. H-2693 also
      preserved cardiac contractile function and attenuated the IR-induced lipid
      peroxidation (TBARS formation) and protein oxidation (carbonyl content). Western
      blot revealed that H-2693 propagated the phosphorylation of Akt (activation) and
      its downstream substrate glycogen synthase kinase-3beta (GSK-3beta, inactivation)
      compared to untreated IR. Parallel treatment with the phosphatidylinositol-3
      kinase (upstream activator of Akt) inhibitor wortmannin (100 nM) abolished the
      beneficial effects of H-2693 on energetics and function, and reduced Akt and GSK
      3beta phosphorylation. As a result of the antiapoptotic impacts of Akt
      activation, H-2693 decreased caspase-3 activity, which was neutralized by
      wortmannin. Here we first demonstrated that a free radical-entrapping compound
      could activate the prosurvival Akt pathway beyond its proven ability to scavenge
      reactive oxygen species. In conclusion, the favorable influence of H-2693 on
      signaling events during IR may have considerably contributed to its
      cardioprotective effect.

PMID- 14572609
TI  - Two subpopulations of mitochondria in the aging rat heart display heterogenous
      levels of oxidative stress.
AB  - Cardiac mitochondria are composed of two distinct subpopulations: one beneath the
      sarcolemma (subsarcolemmal mitochondria: SSM), and another along the myofilaments
      (interfibrillary mitochondria: IFM). Previous studies suggest a preferential loss
      of IFM function with age; however, the age-related changes in oxidative stress in
      these mitochondrial subpopulations have not been examined. To this end, the
      changes in mitochondrial antioxidant capacity, oxidant output, and oxidative
      damage to Complex IV in IFM and SSM from young and old rats were studied. Results
      show no apparent differences in any parameters examined between IFM and SSM from
      young rats. However, relative to young, only IFM from old rats had a
      significantly higher rate of oxidant production and a decline in mitochondrial
      ascorbate levels and GSH redox status. The age-related decline in mitochondrial
      antioxidant capacity in IFM was accompanied by a marked loss in glutaredoxin and
      GSSG reductase activities, suggesting a diminished reductive capacity in IFM with
      age. Moreover, the loss in Complex IV activity was limited to the IFM of old
      rats, which was accompanied by a 4-fold increase in 4-hydroxynonenal-modified
      Complex IV. Thus, mitochondrial decay is not uniform and further indicates that
      myofibrils may be uniquely under oxidative stress in the aging heart.

PMID- 14572610
TI  - Effect of olive oil minor components on oxidative stress and arachidonic acid
      mobilization and metabolism by macrophages RAW 264.7.
AB  - Minor components of virgin olive oil may explain the healthy effects of the
      Mediterranean diet on the cardiovascular system and cancer development. The
      uncontrolled production of reactive oxygen species (ROS) and arachidonic acid
      (AA) metabolites contributes to the pathogenesis of cardiovascular disease and
      cancer, and inflammatory cells infiltrated in the atheroma plaque or tumor are a
      major source of ROS and eicosanoids. We aimed to determine the effects of
      squalene, beta-sitosterol, and tyrosol, which are representative of the
      hydrocarbons, sterols, and polyphenols of olive oil, respectively, on superoxide
      anion (O2(-)), hydrogen peroxide (H2O2), and nitric oxide (*NO) levels. We also
      studied AA release and eicosanoid production by phorbol esters (PMA)-stimulated
      macrophages RAW 264.7. beta-Sitosterol and tyrosol decreased the O2(-) and H2O2
      production induced by PMA, and tyrosol scavenged the O2(-) released by a ROS
      generating system. These effects were correlated with the impairment of [3H]AA
      release, cyclooxygenase-2 (COX-2) expression, and prostaglandin E(2)/leukotriene
      B(4) synthesis in RAW 264.7 cultures stimulated by PMA. beta-Sitosterol exerted
      its effects after 3-6 h of preincubation. Tyrosol inhibited the [3H]AA release
      induced by exogenous ROS. beta-Sitosterol and tyrosol also reduced the *NO
      release induced by PMA, which was correlated with the impairment of inducible
      nitric oxide synthase (iNOS) levels. This may be correlated with the modulation
      of NF-kappaB activation. Further studies are required to gain more insight into
      the potential healthy effects of minor components of extra virgin olive oil.

PMID- 14572611
TI  - Apoptosis of lymphocytes induced by chromium(VI/V) is through ROS-mediated
      activation of Src-family kinases and caspase-3.
AB  - Mechanistic insights into Cr(VI)-induced carcinogenicity and possible implication
      of Cr(V) species formed by the redox reactions of chromium-bearing species have
      attracted interest. We have previously demonstrated that when human peripheral
      blood lymphocytes are exposed to the Cr(V) complexes, viz., sodium bis(2-ethyl-2
      hydroxybutyrato)oxochromate(V), Na[Cr(V)O(ehba)(2)] and sodium bis(2-hydroxy-2
      methylbutyrato)oxochromate(V), Na[Cr(V)O(hmba)(2)], apoptosis and formation of
      reactive oxygen species (ROS) are observed. The molecular mechanisms involving
      cellular signaling pathways leading to apoptosis are addressed in the present
      study. Treatment of lymphocytes with Na[Cr(V)O(ehba)(2)] and K(2)Cr(2)O(7) leads
      to the activation of the Src-family protein tyrosine kinases namely, p56(lck),
      p59(fyn), and p56/53(lyn), which then activates caspase-3, both of which are
      under the partial influence of ROS. Inhibition of the Src-family tyrosine kinases
      activity by PP2 and of caspase-3 by Z-DEVD-FMK reverses apoptosis, thereby
      suggesting their importance. Antioxidants only partially reverse the apoptosis
      induced by Cr(VI/V), suggesting that pathways other than those induced by ROS
      cannot be ruled out. Although the complex, Na[Cr(V)O(ehba)(2)] is known to be
      relatively stable in aqueous solutions, previous studies have shown that the
      Cr(V) complex, Na[Cr(V)O(ehba)(2)] disproportionates to Cr(VI) and Cr(III) forms
      at pH 7.4 through complex mechanistic processes. Dynamics studies employing EPR
      data show that the Cr(V) state in Na[Cr(V)O(ehba)(2)] is relatively more stable
      in RPMI-1640 medium containing plasma. Formation of ROS during the reaction of
      redox partners with Na[Cr(V)O(ehba)(2)] is an early event and compares favorably
      in kinetic terms with the reported rate processes for disproportionation. This
      investigation presents evidence for the direct implication of Cr(V) in Cr(VI)
      induced apoptosis of lymphocytes.

PMID- 14572612
TI  - Embryonic fibroblasts from Gpx4+/- mice: a novel model for studying the role of
      membrane peroxidation in biological processes.
AB  - A previous study using mice null for Gpx4 indicates that PHGPx plays a critical
      role in antioxidant defense and is essential for the survival of the mouse. In
      the present study, we further analyzed the stress response of MEFs (murine
      embryonic fibroblasts) derived from mice heterozygous for the Gpx4 gene (Gpx4(+/
      ) mice). MEFs from Gpx4(+/-) mice have a 50% reduction in PHGPx expression
      without any changes in the activities of other major antioxidant defense enzymes.
      Compared to MEFs from Gpx4(+/+) mice, MEFs from Gpx4(+/-) mice were more
      sensitive to exposure to the oxidizing agent t-butyl hydroperoxide (t-BuOOH), and
      t-BuOOH exposure induced increased apoptosis in MEFs from Gpx4(+/-) mice. When
      cultured at low cell density, MEFs from Gpx4(+/-) mice also showed retarded
      growth under normal culture conditions (20% oxygen) that was reversed by
      culturing under low oxygen (2% oxygen). In addition, oxidative damage was
      increased in the MEFs from the Gpx4(+/-) mice, as indicated by increased levels
      of F(2)-isoprostanes and 8-oxo-2-deoxyguanosine in these cells. Our data
      demonstrate that MEFs from Gpx4(+/-) mice are more sensitive to oxidative stress
      because of reduced expression of PHGPx.

PMID- 14572613
TI  - Overexpression of Prdx6 reduces H2O2 but does not prevent diet-induced
      atherosclerosis in the aortic root.
AB  - The mammalian 1-Cys peroxiredoxin (Prdx6) is a unique member of the peroxiredoxin
      family of proteins capable of protecting cells from metal-catalyzed oxidative
      damage. We recently identified Prdx6 as a candidate for the quantitative trait
      locus Ath1, a gene responsible for a difference in diet-induced atherosclerosis
      susceptibility in mice. To investigate the role of Prdx6 in atherosclerosis, we
      generated transgenic mice that overexpress the Prdx6 allele from the Ath1
      resistant 129/SvJ strain on an Ath1-susceptible C57BL/6J background. These mice
      expressed significantly elevated levels of Prdx6 mRNA and protein in multiple
      tissues including liver, aorta, and peritoneal macrophages, which accumulated
      significantly lower levels of hydrogen peroxide, revealing an enhanced
      antioxidant activity in these mice. However, overexpression of Prdx6 had no
      protective effect on LDL oxidation in vitro, and transgenic mice fed an
      atherogenic diet for 10 weeks did not possess an increased resistance to
      atherosclerosis nor did they maintain the high prediet plasma HDL levels
      consistent with the Ath1-resistant phenotype. In addition, the Prdx6 allele from
      the susceptible strain was shown to have a higher antioxidant activity than that
      of the resistant strains. These data suggest that the increased peroxidase
      activity attributable to Prdx6 overexpression in transgenic mice is not
      sufficient to protect mice from atherosclerosis, and that Prdx6 is not likely to
      be the gene underlying Ath1.

PMID- 14572614
TI  - Protective effects of green tea polyphenols on human HepG2 cells against
      oxidative damage of fenofibrate.
AB  - The aim of this work was to investigate the protective effects of green tea
      polyphenols on the cytotoxic effects of hypolipidemic agent fenofibrate (FF), a
      peroxisome proliferator (PP), in human HepG2 cells. The results showed that high
      concentrations of FF induced human HepG2 cell death through a mechanism involving
      an increase of reactive oxygen species (ROS) and intracellular reduced
      glutathione (GSH) depletion. These effects were partially prevented by
      antioxidant green tea polyphenols. The elevated expression of PP-activated
      receptors alpha (PPARalpha) in HepG2 cells induced by FF was also decreased by
      treatment with green tea polyphenols. In conclusion, this result demonstrates
      that oxidative stress and PPARalpha are involved in FF cytotoxicity and green tea
      polyphenols have a protective effect against FF-induced cellular injury. It may
      be beneficial for the hyperlipidemic patients who were administered the
      hypolipidemic drug fenofibrate to drink tea or use green tea polyphenols
      synchronously during their treatment.

PMID- 14572615
TI  - Antioxidant capacity of silica hydride: a combinational photosensitization and
      fluorescence detection assay.
AB  - Utilizing a novel combinational technique incorporating spectrafluorometry and
      photosensitization, this analysis determined cell viability and cytotoxicity
      through the introduction of reactive oxygen species and measurement of plasma
      membrane integrity. Chinese hamster ovary and mouse hybridoma cells were treated
      with silica hydride after being photosensitized with singlet oxygen,
      hydroxyl/superoxide, and hydroxyl reactive oxygen species through the use of rose
      Bengal diacetate, malachite green, and N,N'-bis(2-hydroperoxy-2-methoxyethyl)
      1,4,5,8-naphthaldiimide, respectively. The analysis resulted in an easy and
      effective method for quantifying reactive oxygen species reduction and
      characterized the radical reduction efficacy of silica hydride at 97% (+/- 0.68%,
      sigma = 0.84) against singlet oxygen species and over 87% (+/- 0.56%, sigma =
      0.70) for the combination of hydroxyl and superoxide reactive species, and 98%
      (+/- 0.37%, sigma = 0.47) effective for hydroxyl radical species. Nontreated
      photosensitized controls showed less than 1% viability under the same conditions.

PMID- 14572616
TI  - Novel particulate spin probe for targeted determination of oxygen in cells and
      tissues.
AB  - The synthesis and characterization of a new lithium octa-n-butoxy-substituted
      naphthalocyanine radical probe (LiNc-BuO) and its use in the determination of
      concentration of oxygen (oximetry) by electron paramagnetic resonance (EPR)
      spectroscopy are reported. The probe is synthesized as a needle-shaped
      microcrystalline particulate. The particulate shows a single-line EPR spectrum
      that is highly exchange-narrowed with a line-width of 210 mG. The EPR line-width
      is sensitive to molecular oxygen showing a linear relationship between the line
      width and concentration of oxygen (pO(2)) with a sensitivity of 8.5 mG/mmHg. We
      studied a variety of physicochemical and biological properties of LiNc-BuO
      particulates to evaluate the suitability of the probe for in vivo oximetry. The
      probe is unaffected by biological oxidoreductants, stable in tissues for several
      months, and can be successfully internalized in cells. We used this probe to
      monitor changes in concentration of oxygen in the normal muscle and RIF-1 tumor
      tissue of mice as a function of tumor growth. The data showed a rapid decrease in
      the tumor pO(2) with increase of tumor volume. Human arterial smooth muscle
      cells, upon internalization of the LiNc-BuO probe, showed a marked oxygen
      gradient across the cell membrane. In summary, the newly synthesized octa-n
      butoxy derivative of lithium naphthalocyanine has unique properties that are
      useful for determining oxygen concentration in chemical and biological systems by
      EPR spectroscopy and also for magnetic tagging of cells.

PMID- 14572617
TI  - Comparative investigation of superoxide trapping by cyclic nitrone spin traps:
      the use of singular value decomposition and multiple linear regression analysis.
AB  - The kinetics of the reaction between superoxide and the spin trapping agents 5,5
      dimethyl-1-pyrroline N-oxide (DMPO), 5-(diethoxyphosphoryl)-5-methyl-1-pyrroline
      N-oxide (DEPMPO), and 5-tert-butoxycarbonyl-5-methyl-1-pyrroline N-oxide (BMPO)
      were re-examined in the superoxide-generating xanthine/xanthine oxidase system,
      by competition with spontaneous dismutation. The approach used singular value
      decomposition (SVD), multiple linear regression, and spectral simulation. The
      experiments were carried out using a two-syringe mixing arrangement with fast
      scan acquisition of 100 consecutive EPR spectra. Using SVD analysis, the
      extraction of both temporal and spectral information could be obtained from in a
      single run. The superoxide spin adduct was the exclusive EPR active species in
      the case of DEPMPO and BMPO, and the major component when DMPO was used. In the
      latter case a very low concentration of hydroxyl adduct was also observed, which
      did not change during the decay of the DMPO-superoxide adduct. This indicates
      that the hydroxyl radical adduct is not formed from the spontaneous decay of the
      superoxide radical adduct, as has been previously suggested [correction]. It was
      established that in short-term studies (up to 100 s) DMPO was the superior spin
      trapping agent, but for reaction times longer than 100 s the other two spin traps
      were more advantageous. The second order rate constants for the spin trapping
      reaction were found to be DMPO (2.4 M(-1)s(-1)), DEPMPO (0.53 M(-1)s(-1)), and
      BMPO (0.24 M(-1)s(-1)) determined through competition with spontaneous
      dismutation of superoxide, at pH 7.4 and 20 degrees C.

PMID- 14572618
TI  - Effects of TNFalpha on expression of ICAM-1 in human airway epithelial cells in
      vitro: oxidant-mediated pathways and transcription factors.
AB  - We demonstrate that two different cell-permeable antioxidants, pyrrolidine
      dithiocarbamate (PDTC) and dimethylthiourea (DMTU), inhibit TNFalpha-induced ICAM
      1 surface and gene expression in primary cultures of differentiated normal human
      bronchial epithelial (NHBE) cells. In addition, TNFalpha stimulates binding of
      nuclear proteins to the nuclear factor kappa beta (NFkappaB) and the
      CAAT/enhancer binding protein (C/EBP) consensus sites in the ICAM-1 promoter in
      these cells. Because these transcription factors have been suggested to be
      oxidant-sensitive and important in ICAM-1 expression, the potential involvement
      of reactive oxygen species (ROS) in the response to TNFalpha was investigated.
      Interestingly, neither PDTC nor DMTU altered binding of NFkappaB complexes. In
      contrast, either the proteasome inhibitor carbobenzoxy-L-leucy-L-leucy-L-leucinal
      (MG 132) or the IkappaBalpha inhibitor BAY 11-7082 ablated TNFalpha-induced ICAM
      1 gene expression and MG132 inhibited TNFalpha-induced NFkappaB complexes.
      Surprisingly, either PDTC or DMTU inhibited the binding of TNFalpha-enhanced
      C/EBP complexes to the consensus site directly adjacent to the NFkappaB site.
      These results suggest that although TNFalpha enhances binding of C/EBP and
      NFkappaB complexes in NHBE cells, C/EBP binding seems to involve an oxidant
      dependent mechanism, whereas activation of NFkappaB complexes utilizes the
      ubiquitin-proteasome pathway, a mechanism that seems to be unaltered by the
      presence of antioxidants. Because interference with either signaling pathway
      abrogates TNFalpha-induced ICAM-1 expression, activation of both complexes seems
      to be involved in this response to TNFalpha, but this activation occurs via
      different intracellular pathways.

PMID- 14572619
TI  - Homocysteine metabolism and B-vitamins in schizophrenic patients: low plasma
      folate as a possible independent risk factor for schizophrenia.
AB  - Two apparently unrelated disorders, neural tube defects (NTD) and schizophrenia
      showed increased risks in birth cohorts exposed to famine during early gestation.
      NTD is associated with impaired folate metabolism. We investigated whether
      schizophrenia is also linked with a dysfunctional folate metabolism. In addition
      to the prevalence of the 677C-->T mutation in the 5,10-methylenetetrahydrofolate
      reductase (MTHFR) gene, we compared plasma and red blood cell (RBC) folate,
      vitamin B6, vitamin B12, and homocysteine (Hcy) concentrations of 35
      schizophrenic patients with those of 104 unrelated controls. Schizophrenic
      patients had significantly lower plasma folate concentrations after adjustment
      for Hcy levels, and elevated RBC folate levels compared to controls. Vitamin B6,
      vitamin B12, and Hcy levels did not differ from control values. Plasma folate
      levels below the 10th percentile of controls were associated with an approximate
      4-7-fold (before and after adjustment of folate levels for Hcy, respectively)
      risk of having schizophrenia. In addition, a significant dose-response relation
      between plasma folate concentrations and risk for schizophrenia suggested a
      protective effect by high plasma folate concentrations. Elevated Hcy levels and,
      in line with this finding, homozygosity for the 677C-->T mutation in the MTHFR
      gene were not associated with an increased risk for schizophrenia. Evidence is
      presented suggesting that folate metabolism is disturbed in schizophrenic
      patients, independently of Hcy.

PMID- 14572620
TI  - Exploration of dimensions of psychopathology in neuroleptic-naive patients with
      recent-onset schizophrenia/schizophreniform disorder.
AB  - Previous studies have suggested that schizophrenic psychopathology segregates
      into three orthogonal dimensions, viz., psychosis, negative and disorganization.
      Most of these reports were based on studies on medicated patients with varying
      degrees of chronicity. The present study aimed at exploring the dimensionality of
      psychopathology rated on the Scale for the Assessment of Negative Symptoms (SANS)
      and the Scale for the Assessment of Positive Symptoms (SAPS) in a sample of 43
      neuroleptic-naive patients with recent-onset schizophrenia/schizophreniform
      disorder. Principal Components Analysis (PCA) of SANS and SAPS global ratings,
      excluding inattention but including inappropriate affect as a separate global
      rating, revealed that the symptoms segregated into three dimensions, viz.,
      negative (affective flattening, alogia, avolition anhedonia and inappropriate
      affect), psychosis (delusions and hallucinations) and disorganization (positive
      formal thought disorder and bizarre behavior). Cumulatively these three
      dimensions explained 74.07% of the variance. The results suggest that the three
      dimensions of schizophrenic psychopathology are valid even in neuroleptic-naive,
      recent-onset patients with schizophrenia/schizophreniform disorder. PCA of the
      SANS and SAPS individual items revealed similar findings, but psychotic symptoms
      loaded under two components, thus yielding a four-factor solution; however, this
      observation needs to be confirmed in a larger sample of neuroleptic-naive
      schizophrenic patients.

PMID- 14572621
TI  - Neurological soft signs and neuropsychological performance in patients with first
      episode schizophrenia.
AB  - Neurological soft signs and neuropsychological (NP) impairments are prevalent in
      schizophrenic patients. However, the relationship of these deficits is rarely
      studied, and it remains controversial in what way soft signs influence NP
      performance. The Neurological Evaluation Scale (NES) and a comprehensive
      neuropsychological test battery were used to assess soft signs and cognitive
      functions in 61 first-episode schizophrenic patients. The NP test battery
      included tests such as the California Verbal Learning Test, the Continuous
      Performance Test, the Span of Apprehension Test, the Stroop Color-Word Test, the
      Trail-Making Test and the Wisconsin Card Sorting Test. The NP tests were also
      administered to 87 healthy controls. The first-episode schizophrenic patients
      were split along the median of their NES total score (SS- vs. SS+). The level of
      NP performance and the differences in relative performance (shape of the NP
      profile) on NP functions between the two groups were assessed. The two groups (SS
      vs. SS+) did not differ in any demographic or clinical variable. However, they
      differed in the level of their NP performance (profile mean) but did not show
      differential deficits in NP performance (profile shape). Neurologic soft signs
      influence NP performance and are correlated to a generalized NP deficit rather
      than to any specific NP functions.

PMID- 14572622
TI  - Internalized stigma of mental illness: psychometric properties of a new measure.
AB  - The study evaluated the Internalized Stigma of Mental Illness (ISMI) scale,
      designed to measure the subjective experience of stigma, with subscales measuring
      Alienation, Stereotype Endorsement, Perceived Discrimination, Social Withdrawal
      and Stigma Resistance. The ISMI was developed in collaboration with people with
      mental illnesses and contains 29 Likert items. The validation sample included 127
      mental health outpatients. Results showed that the ISMI had high internal
      consistency and test-retest reliability. Construct validity was supported by
      comparisons against scales measuring related constructs with the same
      methodology. As expected, the ISMI had positive correlations with measures of
      stigma beliefs and depressive symptoms, and it had negative correlations with
      measures of self-esteem, empowerment and recovery orientation. Factor analyses of
      the joint set of items from the ISMI and each scale supported the distinction
      between constructs. Having a validated measure of internalized stigma may
      encourage clinicians to include stigma reduction as a verifiable treatment goal
      in addition to symptom reduction.

PMID- 14572623
TI  - Autoantibodies to serotonin in serum of patients with psychiatric disorders.
AB  - Antibodies to serotonin in serum were investigated by ELISA in patients with
      paranoid schizophrenia (N=27), schizoaffective psychosis (N=38), depression
      (N=67), Alzheimer's disease (N=21), chronic alcoholism (N=43), rheumatoid
      arthritis (N=25), and multiple sclerosis (N=16), and in healthy volunteers
      (N=60). Increased antibody reactivity to serotonin was found in schizoaffective
      psychosis, chronic alcoholism, and rheumatoid arthritis. Decreased antibody
      reactivity to serotonin was found in multiple sclerosis and depression. These
      anti-serotonin antibodies belong to the class of so-called natural
      autoantibodies. Alterations of these natural autoantibodies could indicate a
      disturbance to the immune system. It is possible that these antibodies could also
      influence receptor function. Autoantibodies to neurotransmitters in a wide
      spectrum of psychiatric disorders have not previously been reported.

PMID- 14572624
TI  - Mineralization of the basal ganglia: implications for neuropsychiatry, pathology
      and neuroimaging.
AB  - This article examines the evidence for and against the existence of basal ganglia
      mineralization as a defined clinico-pathological entity. In reviewing the
      literature on basal ganglia mineralization, this article emphasizes evidence
      derived from different neuroimaging modalities, genetics, metabolic studies,
      postmortem series and their possible neuropsychiatric correlates. Relevant
      articles were collected through Medline and Index Medicus searches. Researchers
      have encountered multiple difficulties in accepting basal ganglia mineralization
      as a distinct entity. This syndrome lacks set clinical criteria or a unique
      etiology; not surprisingly, numerous articles have applied varied definitions.
      Because many of the reported cases have not been examined postmortem, both the
      extent and nature of their mineralization remains uncertain. Furthermore,
      researchers have considered small foci of basal ganglia mineralization a normal
      phenomenon of aging. However, when brain deposits are extensive, they are
      associated with a set of age-dependent, progressive clinical symptoms. They
      include cognitive impairment, extrapyramidal symptoms and psychosis. Most cases
      are related to abnormalities of calcium metabolism, but rare familial cases of
      idiopathic origin have been reported. Overabundant mineralization of the brain is
      judged pathological based on its amount, distribution and accompanying clinical
      symptoms. Although its relation with calcium dysregulation is well known, modern
      studies have emphasized abnormalities of iron and dopamine metabolism. The
      authors suggest that these metabolic abnormalities may link basal ganglia
      mineralization to psychotic symptomatology.

PMID- 14572625
TI  - Dopamine receptor D2 -141C Insertion/Deletion polymorphism in a Finnish
      population with schizophrenia.
AB  - We examined the occurrence of the -141C Ins/Del polymorphism in 93 Finnish
      patients with schizophrenia. In comparison with previous studies with Japanese
      and Caucasian populations, the incidence of this polymorphism was unexpectedly
      low. The findings suggest that the frequency of the -141C Ins/Del polymorphism is
      lower in Northern Europe compared to other Caucasian and Japanese populations.

PMID- 14572626
TI  - Basal norepinephrine in depersonalization disorder.
AB  - In contrast to the noradrenergic dysregulation described in PTSD, little is known
      regarding noradrenergic function in dissociative disorders. The purpose of this
      preliminary study was to investigate basal norepinephrine in depersonalization
      disorder (DPD). Nine subjects with DSM-IV DPD, without lifetime PTSD, were
      compared to nine healthy comparison (HC) subjects. Norepinephrine was measured
      via 24-h urine collection and three serial plasma determinations. Groups did not
      differ significantly in plasma norepinephrine levels. Compared to the HC group,
      the DPD group demonstrated significantly higher urinary norepinephrine, only
      prior to covarying for anxiety. The DPD group also demonstrated a highly
      significant inverse correlation between urinary norepinephrine and
      depersonalization severity (r=-0.88). Norepinephrine and cortisol levels
      (reported in a prior study) were not intercorrelated. We concluded that although
      dissociation accompanied by anxiety was associated with heightened noradrenergic
      tone, there was a marked basal norepinephrine decline with increasing severity of
      dissociation. The findings are in concordance with the few reports on autonomic
      blunting in dissociation and merit further investigation.

PMID- 14572627
TI  - Characteristics of drug addicts who attempt suicide.
AB  - The aim of the study was to further describe the characteristics of drug
      dependent patients who attempt suicide. Thus, 449 drug-dependent patients were
      interviewed about whether or not they had ever attempted suicide and about their
      family history of suicidal behavior. Patients completed the Childhood Trauma
      Questionnaire and the Eysenck Personality Questionnaire, and were interviewed
      with the Addiction Severity Index (ASI). It was found that patients who had
      attempted suicide (N=175) were significantly younger than patients who had never
      attempted suicide (N=274). Significantly more of the patients who had attempted
      suicide were female; had a family history of suicide; and had a lifetime history
      of major depression, of having received antidepressant medication, and of
      alcoholism. Also, patients who had attempted suicide had significantly higher
      scores for childhood trauma, psychoticism, neuroticism and introversion, as well
      as higher ASI psychiatric composite scores. These results suggest that social,
      personality, family, developmental and psychiatric risk factors may predispose to
      suicidal behavior in drug-dependent individuals.

PMID- 14572628
TI  - Photoelectric studies of the transmembrane charge transfer reactions in
      photosystem I pigment-protein complexes.
AB  - The results of studies of charge transfer in cyanobacterial photosystem I (PS I)
      using the photoelectric method are reviewed. The electrogenicity in the PS I
      complex and its interaction with natural donors (plastocyanin, cytochrome c(6)),
      natural acceptors (ferredoxin, flavodoxin), or artificial acceptors and donors
      (methyl viologen and other redox dyes) were studied. The operating dielectric
      constant values in the vicinity of the charge transfer carriers in situ were
      calculated. The profile of distribution of the dielectric constant along the PS I
      pigment-protein complex (from plastocyanin or cytochrome c(6) through the
      chlorophyll dimer P700 to the acceptor complex) was estimated, and possible
      mechanisms of correlation between the local dielectric constant and electron
      transfer rate constant were discussed.

PMID- 14572629
TI  - Differential interaction of the two cholesterol-dependent, membrane-damaging
      toxins, streptolysin O and Vibrio cholerae cytolysin, with enantiomeric
      cholesterol.
AB  - Membrane cholesterol is essential to the activity of at least two structurally
      unrelated families of bacterial pore-forming toxins, represented by streptolysin
      O (SLO) and Vibrio cholerae cytolysin (VCC), respectively. Here, we report that
      SLO and VCC differ sharply in their interaction with liposome membranes
      containing enantiomeric cholesterol (ent-cholesterol). VCC had very low activity
      with ent-cholesterol, which is in line with a stereospecific mode of interaction
      of this toxin with cholesterol. In contrast, SLO was only slightly less active
      with ent-cholesterol than with cholesterol, suggesting a rather limited degree of
      structural specificity in the toxin-cholesterol interaction.

PMID- 14572630
TI  - Solution structure of epiregulin and the effect of its C-terminal domain for
      receptor binding affinity.
AB  - Epiregulin (EPR), a novel member of epidermal growth factor (EGF) family, is a
      ligand for ErbB-1 and ErbB-4 receptors. The binding affinity of EPR for the
      receptors is lower than those of other EGF-family ligands. The solution structure
      of EPR was determined using two-dimensional nuclear magnetic resonance
      spectroscopy. The secondary structure in the C-terminal domain of EPR is
      different from other EGF-family ligands because of the lack of hydrogen bonds.
      The structural difference in the C-terminal domain may provide an explanation for
      the reduced binding affinity of EPR to the ErbB receptors.

PMID- 14572631
TI  - Novel types of two-domain multi-copper oxidases: possible missing links in the
      evolution.
AB  - An analysis of the genome sequence database revealed novel types of two-domain
      multi-copper oxidases. The two-domain proteins have the conspicuous combination
      of blue-copper and inter-domain trinuclear copper binding residues, which is
      common in ceruloplasmin and ascorbate oxidase but not in nitrite reductase, and
      therefore are considered to retain the characteristics of the plausible ancestral
      form of ceruloplasmin and ascorbate oxidase. A possible evolutionary relationship
      of these proteins is proposed.

PMID- 14572632
TI  - Subcellular localization and mechanisms of nucleocytoplasmic distribution of
      p202, an interferon-inducible candidate for lupus susceptibility.
AB  - Increased expression of p202 (52 kDa), an interferon (IFN)-inducible murine
      protein, in splenic cells (B- and T-cells) derived from female mice of the lupus
      prone strains is correlated with increased susceptibility to develop systemic
      lupus erythematosus. However, the molecular mechanisms remain unclear. Our
      previous studies have indicated that, in IFN-treated fibroblasts, p202 is
      detected both in the cytoplasm and in the nucleus. Moreover, in the cytoplasm, a
      fraction of p202 associates with a membranous organelle. Here we report that, in
      the cytoplasm, a fraction of p202 associated with mitochondria. Additionally, we
      found that the constitutive p202 is primarily detected in the cytoplasm.
      Remarkably, the IFN treatment of cells potentiated nuclear accumulation of p202.
      Our observations are consistent with the possibility that IFN signaling regulates
      p202 levels as well as its nucleocytoplasmic distribution. These observations
      will serve as a basis to elucidate the molecular mechanisms by which p202
      contributes to lupus susceptibility.

PMID- 14572633
TI  - Conditional expression of exogenous Bcl-X(S) triggers apoptosis in human melanoma
      cells in vitro and delays growth of melanoma xenografts.
AB  - The Bcl-2-related proteins Bcl-X(L) and Bcl-X(S) represent alternative splice
      products and exert opposite activities in the control of apoptosis, but their
      significance for melanoma is not yet clear. Applying the tetracycline-inducible
      expression system Tet-On, we found overexpression of Bcl-X(S) by itself
      sufficient to induce apoptosis in vitro in stably transfected human melanoma cell
      lines. Combination with proapoptotic agents such as etoposide, pamidronate, and
      ceramide resulted in additive proapoptotic effects, whereas Bcl-X(L) protected
      from apoptosis caused via CD95/Fas stimulation. In nude mice growth of melanoma
      xenotransplants derived from stably transfected cells was significantly reduced
      after induction of Bcl-X(S) by doxycycline. Our results indicate that Bcl-X
      proteins are of major importance for control of apoptosis in malignant melanoma.

PMID- 14572634
TI  - An assessment of ADAMs in bone cells: absence of TACE activity prevents
      osteoclast recruitment and the formation of the marrow cavity in developing long
      bones.
AB  - ADAMs (A Disintegrin And Metalloprotease domain) are metalloprotease-disintegrin
      proteins that have been implicated in cell adhesion, protein ectodomain shedding,
      matrix protein degradation and cell fusion. Since such events are critical for
      bone resorption and osteoclast recruitment, we investigated whether they require
      ADAMs. We report here which ADAMs we have identified in bone cells, as well as
      our analysis of the generation, migration and resorptive activity of osteoclasts
      in developing metatarsals of mouse embryos lacking catalytically active ADAM 17
      [TNFalpha converting enzyme (TACE)]. The absence of TACE activity still allowed
      the generation of cells showing an osteoclastic phenotype, but prevented their
      migration into the core of the diaphysis and the subsequent formation of marrow
      cavity. This suggests a role of TACE in the recruitment of osteoclasts to future
      resorption sites.

PMID- 14572635
TI  - Ligand-induced clathrin-mediated endocytosis of the keratinocyte growth factor
      receptor occurs independently of either phosphorylation or recruitment of eps15.
AB  - Keratinocyte growth factor receptor (KGFR) is a receptor tyrosine kinase
      expressed on epithelial cells. Following ligand binding, KGFR is rapidly
      activated and internalized by clathrin-mediated endocytosis. Among the possible
      receptor substrates which could be involved in the regulation of KGFR endocytosis
      and down-modulation, we analyzed here the eps15 protein in view of the proposed
      general role of eps15 in regulating clathrin-mediated endocytosis as well as that
      of eps15 tyrosine phosphorylation in the control of regulated endocytosis.
      Immunoprecipitation and Western blot analysis showed that activated KGFR was not
      able to phosphorylate eps15, suggesting that eps15 is not a receptor substrate.
      Double immunofluorescence and confocal microscopy revealed that activated KGFR,
      differently from epidermal growth factor receptor (EGFR), did not induce
      recruitment of eps15 to the cell plasma membrane. Microinjection of a monoclonal
      antibody directed against the C-terminal DPF domain which contains the AP2
      binding region of eps15 led to inhibition of both pathways of receptor-mediated
      endocytosis, the EGFR ligand-induced endocytosis and the transferrin constitutive
      endocytosis, but did not appear to block the KGFR ligand-induced internalization.
      Taken together our results indicate that the clathrin-mediated uptake of KGFR is
      not mediated by eps15.

PMID- 14572636
TI  - Protein refolding assisted by self-assembled nanogels as novel artificial
      molecular chaperone.
AB  - Molecular chaperone-like activity for protein refolding was investigated using
      nanogels of self-assembly of cholesterol-bearing pullulan. Nanogels effectively
      prevented protein aggregation (i.e. carbonic anhydrase and citrate synthase)
      during protein refolding from GdmCl denaturation. Enzyme activity recovered in
      high yields upon dissociation of the gel structure in which the proteins were
      trapped, by the addition of cyclodextrins. The nanogels assisted protein
      refolding in a manner similar to the mechanism of molecular chaperones, namely by
      catching and releasing proteins. The nanogels acted as a host for the trapping of
      refolded intermediate proteins. Cyclodextrin is an effector molecule that
      controls the binding ability of these host nanogels to proteins. The present
      nanogel system was also effective at the renaturation of inclusion body of a
      recombinant protein of the serine protease family.

PMID- 14572637
TI  - ING1b decreases cell proliferation through p53-dependent and -independent
      mechanisms.
AB  - ING1b can stimulate cell cycle arrest, repair, senescence, and apoptosis. The
      actions of ING1b are attributed to its activation of the tumor suppressor p53.
      Here we investigate the more subtle effects of ING1b on the cell cycle and DNA
      damage responses in the absence of p53. To this end, we have generated isogenic
      cell lines that expressed ING1b and p53 either individually or in combination
      under the control of inducible promoters. A five- to 10-fold induction of ING1b
      over the endogenous protein in a p53-null H1299 background slightly impairs
      proliferation by increasing the doubling time by approximately 10%.
      Significantly, ectopic expression of ING1b enhanced the G(2)/M DNA damage
      checkpoint induced by adriamycin. We demonstrated that the DNA damage-induced
      cell death mediated by the cooperation between ING1b and p53 was more prominent
      than by the individual proteins alone. In adriamycin-treated cells, p53 was
      stabilized and induced the expression of p21(CIP1/WAF1), but the expression of
      ING1b was not affected. The exact targets of ING1b in the p53-null background are
      not known, but we demonstrated that the transcriptional activities of other
      members of the p53 family, p63alpha and p73alpha, could be activated by ING1b.
      These data indicate that ING1 has a subtle antiproliferative effect even in the
      absence of p53, and ING1b enhances the DNA damage responses through p53-dependent
      and -independent mechanisms.

PMID- 14572638
TI  - alpha-Melanocyte-stimulating hormone inhibits lipopolysaccharide-induced
      biological responses by downregulating CD14 from macrophages.
AB  - Monocytes/macrophages are the first cells involved in inflammation. alpha
      Melanocyte-stimulating hormone (alpha-MSH) is known to possess an anti
      inflammatory role induced by a variety of stimuli; however, the molecular
      mechanisms underlying these effects are not clearly defined. In this report we
      provide evidence that alpha-MSH inhibited serum-activated lipopolysaccharide (SA
      LPS)-induced proteolytic enzyme release, oxidative burst response, reactive
      oxygen intermediate generation, nitric oxide production, and adhesion molecule
      expression in monocyte-derived macrophages. alpha-MSH also inhibited SA-LPS
      induced nuclear transcription factor kappaB activation not only in macrophages,
      but also in a T-cell line and human neutrophils isolated from fresh blood. alpha
      MSH downregulated CD14, but not interleukin-1 receptor, tumor necrosis factor
      receptor 1 or 2 from the surface of macrophages. Anti-CD14 antibody was unable to
      protect alpha-MSH-mediated downregulation of CD14. Overall, our results suggest
      that alpha-MSH exerts its anti-inflammatory effect by a novel mechanism in
      macrophages through downregulating of the endotoxin receptor CD14.

PMID- 14572639
TI  - Lipid diffusion in the thylakoid membranes of the cyanobacterium Synechococcus
      sp.: effect of fatty acid desaturation.
AB  - Thylakoid membranes are crucial to photosynthesis in cyanobacteria and plants. In
      cyanobacteria, genetic modification of membrane lipid composition strongly
      influences cold tolerance and susceptibility to photoinhibition. We have used
      fluorescence recovery after photobleaching to measure the diffusion of a lipid
      soluble fluorescent marker in cells of the cyanobacterium Synechococcus sp. PCC
      7942. We have compared the wild-type strain with a transformant with an increased
      level of fatty acid unsaturation. The transformant showed a six-fold increase in
      the diffusion coefficient for the fluorescent marker at growth temperature. This
      is the first direct measurement of lipid diffusion in a photosynthetic membrane.

PMID- 14572640
TI  - FXRE can function as an LXRE in the promoter of human ileal bile acid-binding
      protein (I-BABP) gene.
AB  - Ileal bile acid-binding protein (I-BABP) is a 14 kDa cytosolic protein which
      binds bile acids with a high affinity. It is thought to be implicated in the
      enterohepatic circulation of bile acids and, hence, in cholesterol homeostasis.
      Using a combination of in vivo and in vitro experiments, we have recently shown
      that I-BABP gene expression can be indirectly up-regulated by cholesterol through
      the activation of sterol-responsive element-binding protein 1c (SREBP1c) by liver
      X-receptor (LXR). We report here that I-BABP can be also a direct target for LXR.
      I-BABP regulation by LXR is maintained when the SREBP binding site is deleted in
      the I-BABP promoter and occurs, in the absence of conventional LXRE sequences,
      through an IR1 sequence previously identified as a farnesoid X-receptor
      responsive element (FXRE). Electrophoretic mobility shift assays demonstrated
      that the LXR/RXR heterodimer specifically recognizes the FXRE. Collectively,
      these data strongly suggest that LXR can regulate the I-BABP gene by both direct
      and indirect mechanisms.

PMID- 14572641
TI  - Interferon alpha inhibits the nuclear factor kappa B activation triggered by X
      gene product of hepatitis B virus in human hepatoma cells.
AB  - X gene product of hepatitis B virus (HBV) (HBx) regulates many transcription
      factors including nuclear factor kappa B (NF-kappaB) and plays a key role in
      hepatocarcinogenesis. In this study, we demonstrated that the expression of full
      HBV genome and HBx gene similarly stimulated the transcriptional activity of NF
      kappaB in HuH-7 human hepatoma cells, and that interferon (IFN)-alpha as well as
      dominant negative mutant of IkappaB kinase-alpha effectively inhibited the HBx
      mediated NF-kappaB activation, but IFN-gamma did not. These results suggest that
      IFN-alpha may have a function to block the NF-kappaB activating pathway triggered
      by HBx in HBV hepatocytes.

PMID- 14572642
TI  - R25 is an intracellular membrane receptor for a snake venom secretory
      phospholipase A(2).
AB  - Ammodytoxin is a presynaptically neurotoxic (beta-neurotoxic) snake venom
      secretory phospholipase A(2) (sPLA(2)). We detected a 25 kDa protein which binds
      the toxin with very high affinity (R25) in porcine cerebral cortex. Here we show
      that R25 is an integral membrane protein with intracellular localisation. It is
      the first sPLA(2) receptor known to date that localises to intracellular
      membranes. Centrifugation on sucrose gradients was used to fractionate porcine
      cerebral cortex. The subcellular composition of the fractions was determined by
      following the distribution of organelle-specific markers. The distribution of R25
      in the fractions matched the distribution of the mitochondrial marker succinate
      dehydrogenase, but not the markers for plasma membrane, lysosomes, endoplasmic
      reticulum, synaptic and secretory vesicles. R25 most likely resides in
      mitochondria, which are known to be targets for sPLA(2) neurotoxins in the nerve
      ending and are potentially implicated in the process of beta-neurotoxicity.

PMID- 14572643
TI  - Structural requirements for nuclear localization of GCMa/Gcm-1.
AB  - GCM proteins constitute a small transcription factor family. Nuclear localization
      of Drosophila GCM is mediated by a typical bipartite nuclear localization
      sequence (NLS) close to the DNA-binding GCM domain. Here, we have analyzed
      nuclear localization of the mammalian GCM proteins. Whereas GCMb/Gcm-2 contained
      a classical bipartite NLS, nuclear localization of GCMa/Gcm-1 was mediated by two
      regions without resemblance to known NLS, one corresponding to the amino-terminal
      part of the GCM domain, the second defined as a tyrosine-and-proline-rich carboxy
      terminal region. Nuclear import was counteracted by an amino-terminal nuclear
      export activity. This complex regulation of subcellular localization has
      important implications for GCMa/Gcm-1 function.

PMID- 14572644
TI  - A prokaryotic glutamate receptor: homology modelling and molecular dynamics
      simulations of GluR0.
AB  - GluR0 is a prokaryotic homologue of mammalian glutamate receptors that forms
      glutamate-activated, potassium-selective ion channels. The topology of its
      transmembrane (TM) domain is similar to that of simple potassium channels such as
      KcsA. Two plausible alignments of the sequence of the TM domain of GluR0 with
      KcsA are possible, differing in the region of the P helix. We have constructed
      homology models based on both alignments and evaluated them using 6 ns duration
      molecular dynamics simulations in a membrane-mimetic environment. One model, in
      which an insertion in GluR0 relative to KcsA is located in the loop between the
      M1 and P helices, is preferred on the basis of lower structural drift and
      maintenance of the P helix conformation during simulation. This model also
      exhibits inter-subunit salt bridges that help to stabilise the TM domain
      tetramer. During the simulation, concerted K(+) ion-water movement along the
      selectivity filter is observed, as is the case in simulations of KcsA. K(+) ion
      exit from the central cavity is associated with opening of the hydrophobic gate
      formed by the C-termini of the M2 helices. In the intact receptor the opening of
      this gate will be controlled by interactions with the extramembranous ligand
      binding domains.

PMID- 14572645
TI  - A binding event converted into a folding event.
AB  - We have designed a chimeric protein by connecting a circular permutant of the
      alpha-spectrin SH3 domain to the proline-rich decapeptide APSYSPPPPP with a three
      residue link. Our aim was to obtain a single-chain protein with a tertiary fold
      that would mimic the binding between SH3 domains and proline-rich peptides. A
      comparison of the circular-dichroism and fluorescence spectra of the purified
      chimera and the SH3 circular permutant showed that the proline-rich sequence
      occupies the putative SH3 binding site in a similar conformation and with
      comparable interactions to those found in complexes between SH3 and proline-rich
      peptides. Differential scanning calorimetry indicated that the interactions in
      the binding motif interface are highly cooperative with the rest of the structure
      and thus the protein unfolds in a two-state process. The chimera is more stable
      than the circular permutant SH3 by 6-8 kJ mol(-1) at 25 degrees C and the
      difference in their unfolding enthalpy is approximately 32 kJ mol(-1), which
      coincides with the values found for the binding of proline-rich peptides to SH3
      domains. This type of chimeric protein may be useful in designing SH3 peptide
      ligands with improved affinity and specificity.

PMID- 14572646
TI  - Structurally conserved alpha-neurotoxin genes encode functionally diverse
      proteins in the venom of Naja sputatrix.
AB  - The structure and organization of the genes encoding the long-chain neurotoxins
      and four other isoforms of weak neurotoxins in the venom of Naja sputatrix are
      reported. The genes contained three exons interrupted by two introns, a structure
      similar to other members of the three-finger toxin family. The proteins encoded
      by these genes, however, show varied affinity towards nicotinic acetylcholine
      receptors. Phylogenetic analysis of these genes showed that the weak neurotoxin
      gene is confined to a distinct group. We also observe that specific mutations of
      the gene provide the diversity in function in these toxins while maintaining a
      common structural scaffold. This forms the first report where the molecular basis
      of evolution of postsynaptic neurotoxins from an ancestral gene can be
      demonstrated using the same species of snake.

PMID- 14572647
TI  - The positive charge at Lys-288 of the glucagon-like peptide-1 (GLP-1) receptor is
      important for binding the N-terminus of peptide agonists.
AB  - Lysine-288 in the glucagon-like peptide-1 receptor was predicted to be ideally
      positioned to play a role in hormone binding. Subsequent mutation of Lys-288 to
      Ala or Leu greatly reduced hormone affinity, while substitution with Arg had
      minimal effect. Compared to wild type, the Lys288-Ala receptor had a reduced
      affinity for three peptide ligands with complete N-terminal sequences but not for
      their N-truncated analogues. Hence, the role of this positively charged residue,
      which is conserved at the equivalent position in all other Family B receptors,
      was determined to be important for receptor interaction with the N-terminal eight
      residues of peptide agonists.

PMID- 14572648
TI  - FRAT1 peptide decreases Abeta production in swAPP(751) cells.
AB  - Recently, LiCl has been shown to inhibit amyloid beta peptide secretion in
      association with diminished glycogen synthase kinase beta (GSK3beta) activity.
      However, it remains unclear if direct inhibition of GSK3beta activity will result
      in decreased Abeta production. Frequently rearranged in advanced T-cell lymphomas
      1 (FRAT1) protein is a negative regulator of GSK3alpha/beta kinase activity. To
      examine whether direct inhibition of GSK3alpha/beta kinase activity can lower
      Abeta production, a FRAT1 peptide was expressed in swAPP(751) cells that produce
      high levels of Abeta. Our data demonstrate that cellular expression of FRAT1
      peptide in swAPP(751) cells increases both GSK3alpha and beta phosphorylation on
      Ser21 and Ser9, respectively, while inhibiting kinase activity of both isoforms.
      Moreover, as a result of FRAT1 expression, the production of both total Abeta and
      Abeta(1-42) was significantly decreased. Thus, we provide evidence that direct
      regulation of GSK3alpha/beta by FRAT1 peptide significantly decreases Abeta
      production in swAPP(751) cells.

PMID- 14572649
TI  - Determination of the cleavage sites in SulA, a cell division inhibitor, by the
      ATP-dependent HslVU protease from Escherichia coli.
AB  - HslVU is an ATP-dependent protease from Escherichia coli and known to degrade
      SulA, a cell division inhibitor, both in vivo and in vitro, like the ATP
      dependent protease Lon. In this study, the cleavage specificity of HslVU toward
      SulA was investigated. The enzyme was shown to produce 58 peptides with various
      sizes (3-31 residues), not following the 'molecular ruler' model. Cleavage
      occurred at 39 peptide bonds preferentially after Leu in an ATP-dependent manner
      and in a processive fashion. Interestingly, the central and C-terminal regions of
      SulA, which are known to be important for the function of SulA, such as
      inhibition of cell division and molecular interaction with certain other
      proteins, were shown to be preferentially cleaved by HslVU, as well as by Lon,
      despite the fact that the peptide bond specificities of the two enzymes were
      distinct from each other.

PMID- 14572650
TI  - Inhibition of influenza A virus sialidase activity by sulfatide.
AB  - Sulfatide, which binds to influenza A viruses and prevents the viral infection,
      was found to inhibit the sialidase activities of influenza A viruses in a pH
      dependent manner. The kinetic parameters of the effect of sulfatide on the
      sialidase activities of human influenza A viruses using fluorometric assay
      indicated that sulfatide was a powerful and non-competitive type inhibitor in low
      pH conditions.

PMID- 14572651
TI  - Evidence that elastase is the TNF-R75 shedding enzyme in resting human
      polymorphonuclear leukocytes.
AB  - We previously showed that a metalloprotease and a serine protease mediate
      shedding of the TNF-R75 (75-kDa tumor necrosis factor receptor) in neutrophils.
      Here we show that elastase is the TNF-R75 solubilizing serine protease. Release
      of the TNF-R75 by resting cells was almost totally inhibited by the serine
      protease inhibitor diisopropylfluorophosphate (DFP), by two synthetic, chemically
      unrelated, elastase-specific inhibitors and by alpha1-protease inhibitor. Release
      after TNF or FMLP (N-formyl-L-methionyl-L-leucyl-L-phenylalanine) stimulation was
      blocked by DFP and a metalloprotease inhibitor used in combination. Supernatants
      from resting neutrophils contained a 28-kDa fragment of the receptor, compatible
      with that generated by elastase, whose appearance was inhibited by DFP. Upon FMLP
      stimulation, the release of 28-kDa and 40-kDa fragments was observed, which was
      inhibited by DFP and a metalloprotease inhibitor, respectively. We conclude that
      elastase is the TNF-R75 sheddase of resting neutrophils and that it contributes
      to shedding of this receptor in stimulated cells.

PMID- 14572652
TI  - Formation of glucosylceramide and sterol glucoside by a UDP-glucose-dependent
      glucosylceramide synthase from cotton expressed in Pichia pastoris.
AB  - In plants, glucosylceramide (GlcCer) biosynthesis is poorly understood. Previous
      investigations suggested that sterol glucoside (SG) acts as the actual glucose
      donor for the plant GlcCer synthase (GCS). We addressed this question by
      generating a Pichia pastoris double mutant devoid of GlcCer and SG. This mutant
      was used for heterologous expression of the plant GCS. The activity of the GCS
      resulted in the accumulation of GlcCer and, surprisingly, a small proportion of
      SG. The synthesis of GlcCer in the transformed double mutant shows that the GCS
      is SG-independent, while the detection of SG suggests that in addition to the
      sterol glucosyltransferase, also the GCS may contribute in planta to SG
      biosynthesis.

PMID- 14572653
TI  - Ospdr9, which encodes a PDR-type ABC transporter, is induced by heavy metals,
      hypoxic stress and redox perturbations in rice roots.
AB  - Little is known about the role of pleiotropic drug resistance (PDR)-type ATP
      binding (ABC) proteins in plant responses to environmental stresses. We
      characterised ospdr9, which encodes a rice ABC protein with a reverse (ABC
      TMS(6))(2) configuration. Polyethylene glycol and the heavy metals Cd (20 microM)
      and Zn (30 microM) rapidly and markedly induced ospdr9 in roots of rice
      seedlings. Hypoxic stress also induced ospdr9 in rice roots, salt stress induced
      ospdr9 at low levels but cold and heat shock had no effect. The plant growth
      regulator jasmonic acid, the auxin alpha-naphthalene acetic acid and the
      cytokinin 6-benzylaminopurine triggered ospdr9 expression. The antioxidants
      dithiothreitol and ascorbic acid rapidly and markedly induced ospdr9 in rice
      roots; the strong oxidant hydrogen peroxide also induced ospdr9 but at three
      times lower levels. The results suggested that redox changes may be involved in
      the abiotic stress response regulation of ospdr9 in rice roots.

PMID- 14572655
TI  - Investigation of the functional relevance of the catalytically important Glu(28)
      in family 51 arabinosidases.
AB  - The alpha-L-arabinofuranosidase (AbfD3) from Thermobacillus xylanilyticus is a
      family 51 glycosyl hydrolase. According to classification hierarchy, family 51
      belongs to clan GH-A. While the major GH-A motifs, the catalytic acid-base and
      nucleophile, are conserved in AbfD3, a third catalytically important residue
      (Glu(28)) does not appear to be analogous to any known GH-A motif. To evaluate
      the importance of Glu(28), bioinformatics analyses and site-saturation
      mutagenesis were performed. The results indicate that Glu(28) forms part of a
      family 51 arabinosidase motif which might be functionally homologous to a
      conserved N-terminal motif found in exo-acting enzymes from families 1 and 5.
      Importantly, the data reveal that Glu(28) is a key determinant of substrate
      recognition in the -1 subsite, where it may also play an important role in water
      mediated deglycosylation of the glycosyl-enzyme covalent intermediate.

PMID- 14572654
TI  - Enzymatic nitration of phytophenolics: evidence for peroxynitrite-independent
      nitration of plant secondary metabolites.
AB  - Peroxynitrite (ONOO(-)), a reactive nitrogen species, is capable of nitrating
      tyrosine residue of proteins. Here we show in vitro evidence that plant phenolic
      compounds can also be nitrated by an ONOO(-)-independent mechanism. In the
      presence of NaNO(2), H(2)O(2), and horseradish peroxidase (HRP), monophenolic p
      coumaric acid (p-CA, 4-hydroxycinnamic acid) was nitrated to form 4-hydroxy-3
      nitrocinnamic acid. The reaction was completely inhibited by KCN, an inhibitor
      for HRP. The antioxidant ascorbate suppressed p-CA nitration and its suppression
      time depended strongly on ascorbate concentration. We conclude that nitrogen
      dioxide radical (NO(2)(radical)), but not ONOO(-), produced by a guaiacol
      peroxidase is the intermediate for phytophenolic nitration.

PMID- 14572656
TI  - Anhydrobiosis without trehalose in bdelloid rotifers.
AB  - Eukaryotes able to withstand desiccation enter a state of suspended animation
      known as anhydrobiosis, which is thought to require accumulation of the non
      reducing disaccharides trehalose (animals, fungi) and sucrose (plants), acting as
      water replacement molecules and vitrifying agents. We now show that clonal
      populations of bdelloid rotifers Philodina roseola and Adineta vaga exhibit
      excellent desiccation tolerance, but that trehalose and other disaccharides are
      absent from carbohydrate extracts of dried animals. Furthermore, trehalose
      synthase genes (tps) were not found in rotifer genomes. This first observation of
      animal anhydrobiosis without trehalose challenges our current understanding of
      the phenomenon and calls for a re-evaluation of existing models.

PMID- 14572657
TI  - Motif CXCC in nitrile hydratase activator is critical for NHase biogenesis in
      vivo.
AB  - Nitrile hydratase (NHase) activator from Rhodococcus sp. N-771 is required for
      NHase functional expression. The motif 73CXCC76 in the NHase activator sequence
      was here revealed to be vital for its function by site-directed mutagenesis. All
      three substitutions of the cysteines by serines resulted in a much lower level of
      expression of active NHase. Furthermore, interaction between NHase activator and
      NHase was detected and the critical role of NHase activator was not exhibited in
      the cysteine oxidization process of NHase. These findings suggest NHase activator
      mainly participates in iron trafficking in NHase biogenesis as an iron type
      metallochaperone.

PMID- 14572658
TI  - Growth rate regulation of lac operon expression in Escherichia coli is cyclic AMP
      dependent.
AB  - In contrast to the ribosomal RNA gene expression increasing with growth rate,
      transcription of the lac operon is downregulated by cell growth rate. In
      continuous culture, growth rate regulation of lac promoter was independent of
      carbon substrate used and its location on the chromosome. Since the lac operon is
      activated by cyclic adenosine monophosphate (cAMP), which decreases with
      increasing cell growth rate, expression of plac-lacZ reporter fusion was analyzed
      in cya mutant under various growth conditions. The results demonstrated that
      expression of plac-lacZ in cya mutant was both lower and growth rate independent.
      In addition, ppGpp (guanosine tetraphosphate) was not involved in the mechanism
      of growth rate regulation of the lac promoter. Thus, the results of this study
      indicate that cAMP mediates the growth rate-dependent regulation of lac operon
      expression in Escherichia coli.

PMID- 14572659
TI  - T3JAM, a novel protein that specifically interacts with TRAF3 and promotes the
      activation of JNK(1).
AB  - Previous studies suggest that localization of tumor necrosis factor receptor
      (TNFR)-associated factor (TRAF) family members is important for regulating their
      signal transduction. During a screen for TRAF3-associated proteins that
      potentially alter TRAF3 subcellular localization and enable signal transduction,
      we identified a novel protein, T3JAM (TRAF3-interacting Jun N-terminal kinase
      (JNK)-activating modulator). This protein associates specifically with TRAF3 but
      not other TRAF family members. Coexpression of T3JAM with TRAF3 recruits TRAF3 to
      the detergent-insoluble fraction. More importantly, T3JAM and TRAF3
      synergistically activate JNK but not nuclear factor (NF)-kappaB. Our studies
      indicate that T3JAM may function as an adapter molecule that specifically
      regulates TRAF3-mediated JNK activation.

PMID- 14572660
TI  - The oxidant-responsive diaphorase of Rhodobacter capsulatus is a ferredoxin
      (flavodoxin)-NADP(H) reductase.
AB  - Challenge of Rhodobacter capsulatus cells with the superoxide propagator methyl
      viologen resulted in the induction of a diaphorase activity identified as a
      member of the ferredoxin (flavodoxin)-(reduced) nicotinamide adenine dinucleotide
      phosphate (NADP(H)) reductase (FPR) family by N-terminal sequencing. The gene
      coding for Rhodobacter FPR was cloned and expressed in Escherichia coli. Both
      native and recombinant forms of the enzyme were purified to homogeneity rendering
      monomeric products of approximately 30 kDa with essentially the same
      spectroscopic and kinetic properties. They were able to bind and reduce
      Rhodobacter flavodoxin (NifF) and to mediate typical FPR activities such as the
      NADPH-driven diaphorase and cytochrome c reductase.

PMID- 14572661
TI  - Expression and regulation of NDRG2 (N-myc downstream regulated gene 2) during the
      differentiation of dendritic cells.
AB  - We searched for genes with expressions specific to human monocyte-derived
      dendritic cells (DCs) using differential display reverse transcription-polymerase
      chain reaction, and found that N-myc downstream regulated gene 2 (NDRG2), a
      member of a new family of differentiation-related genes, was expressed in DCs.
      While DCs derived from CD34(+) progenitor cells also showed strong NDRG2
      expression, the corresponding mRNA expression was absent in other cell lines
      including monocytes, B cells, and NK cells. The inhibition of DC differentiation
      by dexamethasone or vitamin D(3) treatment down-regulated the expression of the
      NDRG2 gene in DCs. In addition, gene expression was induced in a myelomonocytic
      leukemia cell line, which is capable of differentiating into DCs in cytokine
      conditioned culture. The level of NDRG2 gene expression in DCs was significantly
      higher than that of other members of the NDRG gene family. Finally, in contrast
      to the stable NDRG2 expression in CD40-stimulated DCs, the induction of DC
      maturation by lipopolysaccharide (LPS) resulted in the down-regulation of NDRG2
      gene expression. This down-regulation is likely to be due to a modification and
      subsequent destabilization of NDRG2 mRNA, because co-treating with actinomycin D
      and LPS significantly blocked this LPS effect. Taken together, our results
      indicate that NDRG2 is expressed during the differentiation of DCs, and that
      NDRG2 gene expression is differentially regulated by maturation-inducing stimuli.

PMID- 14572662
TI  - Pioglitazone reduces monocyte adhesion to vascular endothelium under flow by
      modulating RhoA GTPase and focal adhesion kinase.
AB  - Thiazolidinediones (TZDs), potent peroxisome proliferator-activated receptor
      gamma ligands, have been shown to improve endothelial function in vascular
      diseases. We investigated the effects of pioglitazone, a TZD, on monocyte
      endothelial interaction under flow and found that pretreatment (20 mumol/l, 48 h)
      significantly reduced U937 adhesion to human umbilical vein endothelial cells.
      Integrin expression was not altered, however, the activation of RhoA GTPase was
      significantly reduced after treatment. Further, pioglitazone treatment
      significantly reduced phosphorylation of focal adhesion kinase (FAK) at 925Y, but
      not at 397Y, suggesting a specific role in FAK-dependent signaling. These results
      indicate a novel anti-inflammatory role for this compound.

PMID- 14572663
TI  - Electrostatic interactions across the dimer-dimer interface contribute to the pH
      dependent stability of a tetrameric malate dehydrogenase.
AB  - Malate dehydrogenase (MDH) from the moderately thermophilic bacterium
      Chloroflexus aurantiacus (CaMDH) is a tetrameric enzyme, while MDHs from
      mesophilic bacteria usually are dimers. Using site-directed mutagenesis, we show
      here that a network of electrostatic interactions across the extra dimer-dimer
      interface in CaMDH is important for thermal stability and oligomeric integrity.
      Stability effects of single point mutations (E25Q, E25K, D56N, D56K) varied from 
      1.2 degrees C to -26.8 degrees C, and depended strongly on pH. Gel-filtration
      experiments indicated that the 26.8 degrees C loss in stability observed for the
      D56K mutant at low pH was accompanied by a shift towards a lower oligomerization
      state.

PMID- 14572664
TI  - Osgstu3 and osgtu4, encoding tau class glutathione S-transferases, are heavy
      metal- and hypoxic stress-induced and differentially salt stress-responsive in
      rice roots.
AB  - Glutathione S-transferases (GSTs) have poorly understood roles in plant responses
      to environmental stresses. A polyethylene glycol (PEG)-induced tau class GST was
      identified in rice roots by protein microsequencing. PEG and the heavy metals Cd
      (20 microM), Zn (30 microM), Co and Ni rapidly and markedly induced osgstu4 and
      osgstu3 in rice seedling roots. Osgstu4 and osgstu3 were also induced in roots by
      hypoxic stress but not by cold nor heat shock. Salt stress and abscisic acid
      (ABA) rapidly induced osgstu3 in rice roots, whereas osgstu4 exhibited a late
      salt stress and no ABA response. Salicylic acid, jasmonic acid and the auxin
      alpha-naphthalene acetic acid triggered osgstu4 and osgstu3 expression. Osgstu4
      and osgstu3 were rapidly and markedly induced by the antioxidant dithiothreitol
      and the strong oxidant hydrogen peroxide, which suggested that redox
      perturbations and reactive oxygen species are involved in their stress response
      regulations.

PMID- 14572665
TI  - Regulation of cell adhesion signaling by synthetic glycopolymer matrix in primary
      cultured hepatocyte.
AB  - Control of cell-matrix interactions is a central principle for the design of
      biomaterial in tissue engineering. In this study, we evaluated a synthetic
      glycopolymer, which is recognized by the asialoglycoprotein receptor (ASGPR)
      expressed on the surface of hepatocytes, as an artificial matrix to regulate
      integrin-mediated signaling. The phosphorylation of focal adhesion kinase was
      restricted in hepatocytes cultured on the glycopolymer compared with fibronectin.
      In addition, there was no reorganization of cytoskeleton-related proteins such as
      actin filaments, microtubules, and vinculin in hepatocytes cultured on the
      glycopolymer. DNA synthesis and cyclin D1 expression were suppressed in
      hepatocytes grown on the glycopolymer as compared with those grown on fibronectin
      and collagen. The data suggest that the glycopolymer will be a good artificial
      matrix to regulate integrin-mediated signaling and cell growth through the unique
      ASGPR-carbohydrate interaction.

PMID- 14572666
TI  - Identification of a very long chain polyunsaturated fatty acid Delta4-desaturase
      from the microalga Pavlova lutheri.
AB  - Pavlova lutheri, a marine microalga, is rich in the very long chain
      polyunsaturated fatty acids (VLCPUFAs) eicosapentaenoic (20:5n-3) and
      docosahexaenoic (22:6n-3) acids. Using an expressed sequence tag approach, we
      isolated a cDNA designated Pldes1, and encoding an amino acid sequence showing
      high similarity with polyunsaturated fatty acid front-end desaturases.
      Heterologous expression in yeast demonstrated that PlDES1 desaturated 22:5n-3 and
      22:4n-6 into 22:6n-3 and 22:5n-6 respectively, and was equally active on both
      substrates. Thus, PlDES1 is a novel VLCPUFA Delta4-desaturase. Pldes1 expression
      is four-fold higher during the mid-exponential phase of growth compared to late
      exponential and stationary phases.

PMID- 14572667
TI  - Identification of genes involved in growth inhibition of breast cancer cells
      transduced with estrogen receptor.
AB  - Estrogen receptor alpha (ERalpha)-negative breast cancer cells display an
      aggressive phenotype. We previously showed that adenoviral expression of ERalpha
      in ER-negative breast cancer cells leads to an estrogen-dependent down-regulation
      of the proliferation, which could be of interest to control the growth of such
      cells. In this study, we observed an increase in protein levels of p21 and p27
      cyclin-dependent kinase inhibitors, whereas pRb phosphorylation is strongly
      decreased. Flow cytometry experiments showed a slower transit of cells in G1
      (hormone-independent), a hormone-induced accelerated transit through S phase and
      a possible arrest in G2/M phase. In addition, ERalpha-expressing cells were
      undergoing apoptosis. By using cDNA macroarrays, we identified a novel collection
      of genes regulated by liganded ERalpha potentially regulating cell cycle,
      apoptosis, cell signalling, stress response and DNA repair.

PMID- 14572668
TI  - Prediction of proteinase cleavage sites in polyproteins of coronaviruses and its
      applications in analyzing SARS-CoV genomes.
AB  - Recently, we have developed a coronavirus-specific gene-finding system,
      ZCURVE_CoV 1.0. In this paper, the system is further improved by taking the
      prediction of cleavage sites of viral proteinases in polyproteins into account.
      The cleavage sites of the 3C-like proteinase and papain-like proteinase are
      highly conserved. Based on the method of traditional positional weight matrix
      trained by the peptides around cleavage sites, the present method also
      sufficiently considers the length conservation of non-structural proteins cleaved
      by the 3C-like proteinase and papain-like proteinase to reduce the false positive
      prediction rate. The improved system, ZCURVE_CoV 2.0, has been run for each of
      the 24 completely sequenced coronavirus genomes in GenBank. Consequently, all the
      non-structural proteins in the 24 genomes are accurately predicted. Compared with
      known annotations, the performance of the present method is satisfactory. The
      software ZCURVE_CoV 2.0 is freely available at http://tubic.tju.edu.cn/sars/.

PMID- 14572669
TI  - Selective involvement of TIMP-2 in the second activational cleavage of pro-MMP-2:
      refinement of the pro-MMP-2 activation mechanism.
AB  - A tissue inhibitor of metalloproteinases-2 (TIMP-2)-independent mechanism for
      generating the first activational cleavage of pro-matrix metalloproteinase-2 (MMP
      2) was identified in membrane type-1 MMP (MT1-MMP)-transfected MCF-7 cells and
      confirmed in TIMP-2-deficient fibroblasts. In contrast, the second MMP-2
      activational step was found to be TIMP-2 dependent in both systems. MMP-2
      hemopexin C-terminal domain was found to be critical for the first step
      processing, confirming a need for membrane tethering. We propose that the
      intermediate species of MMP-2 forms the well-established trimolecular complex
      (MT1-MMP/TIMP-2/MMP-2) for further TIMP-2-dependent autocatalytic cleavage to the
      fully active species. This alternate mechanism may supplement the traditional
      TIMP-2-mediated first step mechanism.

PMID- 14572670
TI  - Reg protein in gastric cancer tumour cells.

PMID- 14572672
TI  - What human being cannot see can exist: a message from recent studies of solar
      terrestrial relationships.
AB  - Without the Sun, there would be no life on the Earth. Life was created on this
      planet in such a way that it "matches" with the natural environment and was
      further evolved through the physical/chemical processes, which reflect the state
      of the planet. This paper demonstrates that because of the existence of two
      barriers the Earth possesses, i.e. the atmosphere and the magnetic field, we are
      peacefully sitting on this planet and are not aware everyday of a number of
      potentially dangerous episodes that are taking place only 100 km above the
      Earth's surface. The aurora in the polar sky is one of the visible manifestations
      of the variability of the solar-terrestrial environment. It is imperative to
      realize, however, that what we cannot see by human eyes does not mean that they
      do not exist in reality. For example, during the solar declining phase in terms
      of visible indicators, such as sunspots on the Sun, geomagnetic activity
      resulting from invisible activity in the solar corona reaches a peak.

PMID- 14572671
TI  - Chronomics for chronoastrobiology with immediate spin-offs for life quality and
      longevity.
AB  - Effects of geomagnetic disturbance on heart rate variability (HRV), the 1/f
      fractal scaling in particular, are being assessed in adults living at high
      latitude, where magnetic storms are more frequent and more intense than at lower
      latitudes. The latter may constitute a signal or a proxy, and possibly a
      mechanism underlying both undesirable and desirable effects, depending upon
      circumstances yet to be elucidated. Any circadecadal stage-dependence of
      morbidity and/or mortality from certain conditions such as myocardial infarctions
      remains to be studied in both adult and pediatric populations. Further work could
      thus examine whether any associations of geomagnetic disturbances may account, at
      least in part, through effects upon the circulation, for long-term infra-annual
      changes, possibly anchored in the population's gene pool, observed in a number of
      anthropologic measurements at birth as well as in other population statistics. In
      order to assess the development of several chronome components of the
      electrocardiogram (ECG), around-the-clock ambulatory ECG were recorded from 19
      infants (25 days-3 months of age), 22 children (3-9 years of age), 18 boys and
      girls (10-14 years of age), pubertal boys (15-20 years of age), and 10 young men
      (21-29 years of age). Time- and frequency-domain measures of HRV were obtained by
      spectral analysis, using the maximal entropy method (MEM). The frequency of
      detection of the circadian, circasemidian and circaoctohoran components, with
      periods of about 24, 12 and 8 h, respectively, was compared among the five groups
      for several HRV endpoints, notably 1/f fractal scaling, total spectral power
      within a 5-min span, and its distribution into several frequency regions. A
      circadian component is already detectable in a sizeable proportion of infants and
      children for most of the HRV indices considered. The incidence of detection of
      the circadian component increases with age for the spectral power in different
      frequency regions, notably around 10.5 s ("LF") and around 3.6 s ("HF"); it peaks
      around puberty for 1/f in our data; and it did not detectably change with age for
      the total spectral power. Similar changes with age are not observed for the
      circasemidian or circaoctohoran components. The latter characterizes primarily
      1/f and less so the about 3.6 s power ("HF"). Several aspects of the HRV chronome
      may thus develop differently as a function of age. In 2000, we began a community
      based study named "Longitudinal Investigation of Longevity and Aging in Hokkaido
      County (LILAC study)". The ambulatory blood pressure (BP) of middle-aged
      subjects, aged 40-74 years, was monitored 7-day/24-h, and the cardiovascular and
      neurobehavioral functions of elderly people above 75 years were evaluated. Our
      goal was the prevention of stroke and myocardial infarction and the decline in
      cognitive function of the elderly in a community. Of 115 elderly people recruited
      in a longitudinal community-based study in 2000, 72 completed yearly follow-ups
      in 2002. A cardiovascular score based on BP, pulse wave velocity, and 1-h ECG
      based HRV endpoints served to distinguish between normal, mildly disordered, or
      disordered participants. A comparison of cognitive function in 2002 vs. 2000,
      assessed with the MMSE, HDSR, the Up & Go and Functional Reach tests, gauged any
      effect of social intervention. Cognitive function was maintained or improved,
      especially for people suffering from hypertension, tachycardia, or a decreased
      HRV, suggesting that cardiovascular function is a major factor affecting
      cognitive function.

PMID- 14572673
TI  - Chronomics of tree rings for chronoastrobiology and beyond.
AB  - Gliding spectral windows illustrate the changes as a function of time in the
      relative prominence of signals in a given frequency range, viewed in 3D or as
      surface charts. As an example, the method is applied to a 2,189-year series of
      averages of ring measurements on 11 sequoia trees published by Douglass. Analyses
      of the original data and after filtering reveal, among others, components with
      periods of about 10.5 and 21 years similar to the Schwabe and Hale solar activity
      cycles. An alignment of gliding spectra with a global spectrum serves to define,
      by minima, the ranges of variability around the anticipated Schwabe and Hale
      cycles. This procedure may have more general applicability when dealing with
      ranges of only transiently synchronized, wobbly, and perhaps sometimes free
      running periodicities. Solar activity is known to affect climate and changes in
      climate are reflected to some extent in tree growth. The spectral structure in
      tree rings could serve not only to check any relations of climate with sunspots,
      auroras and more modern measures of solar activity, but also to check any purely
      mathematical extrapolations from the much shorter available actual data on solar
      activity. With such extrapolated series and the data analyzed herein, the task
      remains to align physical and physiological variables to further study the
      influence of natural environmental factors near and far on biota, including
      international battles, which cover an even longer span of 2,556 years.

PMID- 14572674
TI  - Point and interval estimations of circadian melatonin ecphasia in Smith-Magenis
      syndrome.
AB  - An inferential statistical quantification of chronomes (time structures) in the
      range of everyday physiology has earlier revealed changes affecting the circadian
      amplitude of melatonin in the absence of changes in the chronome-adjusted mean
      value (MESOR) or in the acrophase. A chrono-meta-analysis of published data on
      patients with the Smith-Magenis syndrome herein quantifies the average extent of
      shift in the acrophase of the circadian melatonin rhythm, reported earlier by
      others time-macroscopically as an antiphase. Time-microscopically, the phase
      shift averages 9.6 +/- 0.9 h. Circadian melatonin ecphasia complements blood
      pressure ecphasia in non-insulin-dependent diabetes mellitus, associated with
      autonomic dysfunction. The shift in phase of the peak melatonin secretion from
      the night into the day, associated with specific genetic findings, raises basic
      questions concerning the designation of melatonin as a hormone associated with
      darkness. Whether a resetting of the circadian acrophase beyond providing
      melatonin for sleep improvement can provide benefit remains to be investigated.

PMID- 14572675
TI  - Blood pressure variability during 120-day head-down bed rest in humans.
AB  - Influence of physical inactivity and microgravity to periodic structure of blood
      pressure was studied. Six healthy males were kept under head-down bed rest (HDBR)
      for 120 days. Blood pressure and heart rate (HR) were recorded by a portable
      sphygmomanometer and a Holter electrocardiogram, respectively. The results were
      analyzed by spectrum analysis. Phase, amplitude and acrophase of systolic blood
      pressure (SBP) by approximately 24, 12 and 8 h were measured before, 60, 120 day
      and after HDBR. The phase at 24, 12 and 8 h did not show significant changes
      during HDBR, and acrophase showed a tendency to shift to 14:00 after HDBR.
      Amplitude for 24 h tended to attenuate during bed rest (BR), and significantly
      increased after BR. The results of this study suggest that the circadian rhythm
      of SBP and HR were maintained by strict control of sleep, awakening and food
      intake in microgravity model of a long-term BR state. However, the tendency to
      decrease 24-h cyclic amplitude of SBP appeared to be the rhythmic modulation
      related to cardiovascular deconditioning.

PMID- 14572676
TI  - About 7-day (circaseptan) and circadian changes in cold pressor test (CPT).
AB  - We assess circadian (CD) and circaseptan (CS) changes in the blood pressure (BP)
      response to a 1-min immersion of the hand into ice water, the cold pressor test
      (CPT). An about 8 mmHg BP increase in the CPT reported by others for health and
      an elevation >25 mmHg for patients with "hypertension" have been viewed as
      predisease, but variables related to the vascular system exhibit prominent CD, CS
      and circannuals, among other components of their genetically anchored time
      structure or chronome, and may also have to be considered. Hence, a 16-year-old
      adolescent (ML) immersed her hand into ice water every 2-4 h for 2 days and once
      daily in the morning thereafter for 1 week (N = 25), as did, only for <2 days (>
      or =24 h), four adults 20-66 years of age. BP and heart rate (HR) were monitored
      automatically around the clock at 15-min intervals and at 1-min intervals before
      and immediately after the CPT. Data were analyzed by cosinor. The difference
      between the first post-CPT BP value and the mean of the last seven values prior
      to the CPT was a measure of CPT response (at 1-min). Overall, ML's systolic (S)
      BP increased by 8.2 +/- 1.4 mmHg and her diastolic (D) BP by 6.2 +/- 0.9 mmHg (P
      < 0.001). Increases were found in 96% of the tests for SBP, 92% for DBP and 20%
      for HR. There was only one tie for HR (4%), resulting in a HR decrease in 76% of
      CPTs. The BP response to CPT at 1 min was CS-dependent. The CS double amplitudes
      are 12.5 +/- 4.1 for SBP (P = 0.019) and 7.8 +/- 2.8 mmHg for DBP (P = 0.030),
      with acrophases occurring on late Sunday, early Monday (at -50 degrees and -67
      degrees from 00:00 h from Saturday to Sunday for SBP and DBP, respectively, with
      360 degrees identical with 1 week). The response of HR did not allow the
      detection of a CS rhythm (P = 0.969). The CD response peaked in the early morning
      hours; with 24 h identical with 360 degrees and 0 degrees = local midnight, the
      acrophase (phi) for SBP is at -80 degrees and for DBP at -113 degrees, in keeping
      with earlier results from four adult subjects (SBP: -37 degrees; DBP: -42 degrees
      ), individual differences notwithstanding. The average timing of the largest
      overall response of BP to CPT coincides with the timing of the response to other
      stimuli. The CS acrophases coincide with the times of increased
      morbidity/mortality from vascular diseases. Chronomes, time structures broader
      than circadian, notably their about-weekly components, should be considered, not
      only at the extremes of life when the CS and about-half-weekly rhythms are
      particularly prominent in BP and HR but also in interpreting BP responses as a
      gauge of vascular disease status in adolescents.

PMID- 14572677
TI  - Circasemiannual chronomics: half-yearly biospheric changes in their own right and
      as a circannual waveform.
AB  - Geomagnetic activity has a strong half-yearly but no precise yearly component in
      its spectrum, as Armin Grafe suggested nearly half a century ago. We have
      postulated elsewhere that non-photic cycles such as those in geomagnetics may
      have signatures in the biosphere and vice versa that biological rhythms have
      likely counterparts in the physical environment. Accordingly, we document
      phenomena characterized by a prominent about half-yearly variation, re-analyzed
      to constitute the start of a transdisciplinary chronomic (time structural) map,
      aligning these conditions with a half-yearly cycle in the geomagnetic index Kp.
      At least some biospheric phenomena fitted concomitantly with 1- and 0.5-year
      cosine curves exhibit an amplitude (A) ratio of A(0.5-year)/A(1-year) larger than
      unity. Methodologically, it is pertinent that even if data were read off
      published graphs, the resulting analyses were practically the same as those in
      the original data received subsequently. The main point is a circasemiannual
      pattern in status epilepticus, in several morbid oral conditions, in the cell
      density of vasopressin-containing neurons in the human suprachiasmatic nuclei
      (SCN), in circulating melatonin at middle latitudes at night during years of
      minimal solar activity or around noon at high latitudes, and in an unusual
      circasemiannual aspect of a birth-month-dependence of human longevity. Others
      have asked whether annual rhythms in human reproduction are biological,
      sociological or both. We show some other possibilities herein, involving the
      physical environment, hardly to be neglected in the case of open systems. As to
      almost certainly multifactorial circasemiannual rhythms, geomagnetics may also be
      a signal, a proxy or a putative, at least partial mechanism. Geomagnetic activity
      is related in its turn to solar and galactic activity, and may be a marker for
      other cyclic events that affect the biosphere. The similarity of cycle lengths in
      itself can only be a hint prompting the search for causal relations.

PMID- 14572678
TI  - Non-photic, non-thermic circadecadal solar cycle interaction with cardiovascular
      circannual and circasemiannual variation in heated air-conditioned habitat.
AB  - In order to re-examine the extent to which secular circulatory variation can be
      resolved into possibly accountable, if not yet predictable behavior, the 15-year
      record of blood pressure and heart rate of an adult male cardiologist (Y.W.) is
      reanalyzed. Gliding spectral windows with an interval of 4 years progressively
      displaced throughout the data series examine monthly means from August 1987 to
      August 2002. A circannual variation is only intermittent and appears to drift for
      years. A circasemiannual variation is consistent and prominent, yet only for a
      fraction of the record examined. By contrast to the circadian rhythm in blood
      pressure and heart rate, which is reliably detectable in most subjects in
      clinical health, the circannual variation in the human circulation is
      inconsistent and hence should be monitored, as in this case for its assessment as
      one goes, a conclusion that also applies to the circasemiannual variation,
      prominent for years but not detected thereafter. The results prompt the search
      for interactions between the photic, thermic and societal effects of the seasons
      that, if solely pertinent, should yield a consistent 1-year spectral component.
      That non-photic effects may also play an important role may point to modulation
      by solar cycle stage and solar cycle number, perhaps mediated by the solar wind.
      This conclusion is extended in proof to the role played by the most recently
      discovered transannual component in human blood pressure and heart rate, which is
      a probable further signature of the solar wind. The beating of the transannual
      and circannual components documented on another data series may contribute to the
      lack of a consistent 1-year synchronized circannual variation in this case and
      many others.

PMID- 14572679
TI  - Blood pressure self-surveillance for health also reflects 1.3-year Richardson
      solar wind variation: spin-off from chronomics.
AB  - Self-experimentation concerns not only scientists, but also each individual for
      the sake of his/her chronobiologic health and science literacy, eventually to be
      acquired in primary and secondary education. Public education ensures that
      everybody who knows how to read or write can dispense with the service of a
      costly scribe. At all ages, public education can teach equally well how to find
      out whether one's blood pressure (BP) and heart rate (HR) responds to an increase
      in sodium intake with a rise, with no change or with a decrease in BP. This task
      and many others could become a matter of informed self-surveillance. Whenever
      there are inter-individual, sometimes opposite differences in response,
      government-sponsored trials on groups that do not consider such differences
      cannot solve what only the individual can do, at first by help from schools.
      Eventually special institutions may be designed for chronomics, the monitoring,
      interpretation and archivization of chronomes (time structures; from chronos =
      time and nomos = rule) of biological variables, also charged with a demographic
      analyzing and reporting system. Each individual's properly coded record, to guard
      confidentiality, becomes part of a promptly accessible database for one's own
      needs and for society's requirements. What individuals and small groups started
      as chronobiology, what is immediately available on back burners, as a service by
      an international project on the biosphere and the cosmos (BIOCOS)
      (corne001@umn.edu) could become a public system of planned surveillance
      archivization of one's rhythms from womb to tomb. Alterations of a rhythm's
      amplitude or acrophase or of a deterministic or other chaotic endpoint, such as a
      correlation dimension and approximate entropy, or of a standard deviation, among
      a multitude of other endpoints, can signal (in the otherwise neglected normal
      range) reversible risk elevations. If these elevated risks are detected and
      prompt the institution of countermeasures, such prehabilitation can save the cost
      of rehabilitation or of long-term care after morbid events; suffering also can be
      prevented such as that by those who are unlucky enough to helplessly survive a
      massive brain, heart or societal "stroke". As an equally important dividend,
      science gains in basic and applied terms, as illustrated herein by the
      demonstration of a trans-year, an approximately 1.3 to 1.6-year, heretofore
      unknown component of the human BP and HR spectrum, beating with the circannual
      component and characterizing the same data. Chronomically interpreted self
      monitoring is a civic duty for both one's health and everybody's science.

PMID- 14572680
TI  - Altered fractal behavior and heart rate variability in daily life in neurally
      mediated syncope.
AB  - Autonomic imbalance is thought to play an important role in the pathogenesis of
      neurally mediated syncope (NMS). Heart rate variability (HRV) indices and fractal
      dimension derived from 24 h ambulatory electrocardiogram (AECG) reflects the
      cardiac autonomic activity and provides useful information for understanding the
      pathogenesis of NMS. In this study, we sought the cardiac autonomic activity and
      the status of fractal dimension in daily life in patients with NMS. The 24 h
      ambulatory ECG recordings were performed in 36 NMS patients (NMS group) and in 11
      healthy volunteers (CTRL group). Six time domain and frequency domain HRV indices
      were calculated. The regression of log (power) on log (frequency) was also
      calculated and the slope of the regression line (beta) was analyzed in three
      different periods such as total 24 h, awake and sleep phases. The values of mean
      RR, SDNN and SDANN were not significantly different, but the values of S.D.
      index, rMSSD, pNN50 and all the frequency domain HRV indices were significantly
      higher in NMS group than in CTRL group. For 24-h period, there was no significant
      difference in the values of beta. For awake phase, the value of beta was
      significantly higher in NMS group than in CTRL group. For sleep phase, the value
      of beta was significantly lower in NMS group than in CTRL group. Augmented
      autonomic activity and the deterioration of fractal dimension in daily life might
      contribute to the pathogenesis of NMS.

PMID- 14572681
TI  - Can personality traits predict pathological responses to audiovisual stimulation?
AB  - The "Pockemon shock" is the most famous accident in the history of the
      broadcasting industry in Japan. Based on the experiences of this unfortunate
      accident from famous animation program "Pocket Monster", this study focused on
      the psychology and psychosomatics of the patients. A head-mounted display was
      used as the three-dimensional image presentation device and "Descent", a free
      software shooting game, was used as the software. Ten healthy adult male
      volunteers were used in this experiment after obtaining their informed consent.
      The oxygen metabolic change in the anterior lobe of the brain was measured by
      near infrared spectroscopy and recorded on an electrocardiogram. The mental
      scaling tendency of the object was analyzed using the type A behavior pattern and
      the hostility scaling. The Cook and Medley hostility (HO) scale from the
      Minnesota multiphasic personality inventory (MMPI) was also used in this
      experiment. From this scaling methodology, the paranoid scale, cynicism scale,
      lie scale, social support quality and social support quantity were calculated.
      All measured time series data were kept in the normal range, and no fatal
      arrhythmia or epilepsy were observed during experiments. In some cases, the brain
      oxygen metabolism may completely differ for the objects of Type A and Type B
      behavior patterns. On the whole, correlation did not become significant in type A
      scaling and hostility scaling. In a comparison of the percent changes of the HF
      in HRV with lie scaling, significant negative correlation was observed. The
      social support quantity was calculated from Cook and Medley, and significant
      negative correlations were observed with percent changes of LF/HF in HRV. The lie
      scale and social support quantity are opposite scaling. The sympathetic nervous
      system and parasympathetic nervous system have an opposite function also.
      Therefore, our results showed an interesting phenomenon, when considering the
      relationship between the autonomic function and the pathophysiological reaction
      to the audiovisual stimulations. As for the photo sensitive epilepsy, it was
      reported to be only 5-10% for all patients. Therefore, 90% or more of the cause
      could not be determined in patients who started a morbid response. The results in
      this study suggest that the autonomic function was connected to the mental
      tendency of the objects. By examining such directivity, it is expected that
      subjects, which show morbid reaction to an audiovisual stimulation, can be
      screened beforehand.

PMID- 14572682
TI  - Effects of diaphragmatic breathing on ambulatory blood pressure and heart rate.
AB  - Psychological procedures, such as self-hypnosis in the form of autogenic
      training, have been proposed for correcting a deviant, e.g., high blood pressure
      (BP). In view of the overwhelming evidence for the circadian (CD) stage
      dependence of any treatment effects, the CD stage dependence of the effects of
      diaphragmatic breathing (DB) on BP and heart rate (HR) was explored in data from
      a clinically healthy normotensive subject who, following 3 weeks of ambulatory
      monitoring as a reference standard, measured BP and HR with a manual monitor at 1
      min intervals for 5 min before and after DB (three deep diaphragmatic breaths)
      and who performed DB for about 2 weeks at about 2-h intervals while awake. The 3
      week data series were analyzed by cosinor, involving the least-squares fit of
      cosine curves with periods of 24, 12 and 168 h. A CD rhythm was detected for BP
      and HR (P < 0.001 in each case), peaking in the afternoon. Some about-weekly
      (circaseptan; CS) BP rhythms and 12-h (circasemidian) components were also
      statistically significant. DB was found to reduce systolic (S) BP. Overall, SBP
      decreased by 5.9 +/- 0.8 mmHg (P < 0.001) and diastolic (D) BP by 1.4 +/- 0.8
      mmHg (P < 0.005), while HR remained at about the same average. The effect of DB
      on BP was CD-dependent, the largest response occurring in the afternoon, 2-3 h
      before the peaks in SBP and DBP found in the reference data of the same subject.
      There was also a 5-10% decrease in SBP around the weekend (Friday, Saturday and
      Sunday). The results on a single subject suggest the need to collect similar data
      on others for optimizing by clock-hour, day of the week, and eventually by the
      marker rhythms BP and/or HR the best times for DB and other procedures. The
      personalized best time for people on different work/rest schedules for relaxation
      may be several hours before their BP has reached its highest point in the 24-h
      span. HR may serve as a marker for DB timing, but the effect on HR of DB was only
      of borderline statistical significance in the subject investigated.

PMID- 14572683
TI  - Chronotherapy for cancer.
AB  - Cancer chronotherapy is attracting attention as a novel and logical therapy in
      which anti-cancer drugs are administered with optimal timing according to
      circadian rhythms of anti-cancer action and those of adverse effects on normal
      cells. Advances in chronobiology have identified the suprachiasmatic nucleus
      (SCN) as the center of biological rhythms and the area in which clock genes such
      as PER1, PER2, PER3, CLOCK, BMAL1, TIM, CRY1, CRY2, tau act to generate and
      coordinate biological rhythms. These findings have led to the development of
      chronotherapy. Clinically, patients with advanced gastrointestinal cancer have
      been treated by chronomodulated chemotherapy with good response. For colorectal
      cancer patients with unresectable liver metastases, chronotherapy with l-OHP + 5
      FU + FA (folinic acid) has been reported to allow complete surgical resection of
      liver metastases, resulting in 39-50% 5-year survival. Many believe that
      chronotherapy will become accepted as a refined and advantageous therapeutic
      option for not only cancer but also for other diseases, due to its universally
      applicable principles.

PMID- 14572684
TI  - Does the timing of surgery for breast cancer in relation to the menstrual cycle
      or geomagnetic activity affect prognoses of premenopausal patients?
AB  - We examined the records in 36 breast cancer patients treated between 1990 and
      2001, and compared them for relapse-free survival with reference to the phases of
      menstrual cycle defined by Hrushesky et al. and Senie et al. During the follow-up
      period, seven patients suffered a relapse and one died of another disease without
      relapsed breast cancer. The recurrence rate and relapse-free survival were not
      significantly different with the menstrual timing of surgery. However, patients
      with early breast cancer operated during the follicular phase and those with
      advanced breast cancer resected during the luteal phase appeared to show better
      prognosis than corresponding controls operated during the other phases. On the
      other hand, the correlation between geomagnetic activity and prognosis of breast
      cancer was also investigated. High geomagnetic activity during operation
      significantly affected the prognosis of the disease in an adverse fashion. This
      adverse influence was more marked in the patients operated during the luteal
      period. Since the menstrual cycle has no clear relation to the prognosis of
      breast cancer, the geomagnetic activity might affect them via other pathways than
      the menstrual cycle.

PMID- 14572685
TI  - Transient circadian hyper-amplitude-tension (CHAT) may be intermittent: case
      reports illustrating gliding spectral windows.
AB  - Taking the heart rate (HR) for one cycle, whether to examine behavior in the
      region of periods of 1 s, 1 day, 1 week, 1.3 or 10.5 years, etc., is hazardous.
      Replications, when possible are mandatory for examining altered variability,
      whatever the period(s) involved may be. This replication in the individual, and
      across individuals when the periods are long, measured in decades, may serve for
      diagnosis and treatment. This rule applies in particular to a seemingly transient
      circadian hyper-amplitude-tension (CHAT), an over peer-threshold variability in
      blood pressure (BP), based on the fit of a 24-h cosine curve to time series of
      appropriate length, rather than to a mere snapshot covering just a single day or
      week. Transient CHAT may turn into intermittent CHAT, as determined in two cases
      presented herein. One case of transient CHAT could be so named after a successful
      treatment (Rx) change eliminated CHAT as an effect validated by monitoring at 30
      min intervals for a 7-day span on a new treatment. CHAT disappeared for over 300
      consecutive half-hourly measurements, but thereafter it reappeared. During the
      ensuing nearly continuously monitored 5 years, CHAT continued to appear and
      disappear sometimes without a treatment change. In another case, which was
      responsive to a change in the timing of medication, CHAT also disappeared and
      thereafter reappeared. In a short-term perspective of weeks or months of
      monitoring, CHAT seemed to be transient, but further monitoring again revealed it
      to be intermittent. Cases of intermittent CHAT require follow-up for outcomes by
      comparison with the population at large. Miniaturized instrumentation for their
      detection should be a high priority, but it must be realized that the automatic
      ambulatorily functioning monitors, available at 10% of the regular price through
      a BIOCOS project (corne001@umn.edu), already signify great progress, as compared
      to previously used manual measurements made around the clock by hypertensive
      opinion leaders in medicine from diagnosis to death. On automatically collected
      time series of BP and HR, gliding pergressive spectral windows as such, or such
      pergressive windows aligned further with global spectral windows, visualize the
      changing dynamics involved in health and disease, in the steps of Werner Menzel
      and Paolo Scarpelli.

PMID- 14572686
TI  - Toward chronocardiologic and chronomic insights: dynamics of heart rate
      associated with head-up tilting.
AB  - As a step towards investigating the chronome (i.e. the inferential endpoints of
      chaos, trends and rhythms) of heart rate (HR) variability (HRV), we investigated
      whether the fractality or complexity of HRV is affected by a head-up tilting
      (HUT) test in the morning after an overnight fast. Spectral and non-linear
      analyses of HR were performed on data gathered during an 80 degrees passive HUT
      test in 15 men and 28 women 32.8 +/- 11.5 years of age. The non-linear endpoints
      included the scaling exponents alpha1 (<11 beats) and alpha2 (>11 beats), which
      indicate fractal properties, calculated with detrended fluctuation analysis, and
      the approximate entropy (ApEn), a measure of overall complexity. Passive HUT
      increased alpha1 (from 0.986 +/- 0.217 to 1.370 +/- 0.185; P = 0.0001), but did
      not alter alpha2 (from 0.925 +/- 0.110 to 0.958 +/- 0.130; P = 0.19). A slight
      but statistically significant decrease in ApEn was seen during HUT (from 1.114 +/
      0.131 to 1.013 +/- 0.197; P = 0.002). In the tilt-up position, there was a
      statistically significant negative correlation between alpha1 and ApEn (r = 
      0.490; P < 0.05). In both the supine and the tilt-up position, alpha1 was
      correlated weakly with HF (r = -0.343 and r = -0.322, respectively), and strongly
      with LF/HF (r = 0.557 and r = 0.795), respectively. There was also a negative
      correlation between ApEn and LF/HF (r = -0.406 and r = -0.357, respectively).
      alpha2 did not correlate with any spectral or non-linear measures of HRV. Short
      term fractal properties and complexity of HR were lowered with orthostatic
      stress. Alterations of the autonomic activities could be partly responsible for
      these changes and await extension of such studies to assess the broad spectral
      element of HRV, that includes, with components of approximately 3.6 and
      approximately 10.5 s, cycles with very much lower frequencies, along the scales
      of hours and even years, that critically modulate the mislabeled (only relatively
      high- and low-frequency) components in the range of seconds or minutes.

PMID- 14572687
TI  - Reduction of correlation dimension in human respiration by inhaling a mixture gas
      of 5% carbon dioxide and 95% oxygen.
AB  - In order to investigate the effect of the respiratory control system on
      deterministic behavior in respiration, we used nonlinear analysis in subjects
      breathing a mixture gas of 5% carbon dioxide (CO2) and 95% oxygen (O2) (CO2-mixed
      gas). The respiratory movements during breathing air or CO2-mixed gas in eight
      healthy volunteers were measured. We estimated the values of the correlation
      dimension (D2) in respiratory movement using Grassberger-Procaccia algorithm. The
      respiratory movements during inhaling either air or CO2-mixed gas showed a
      nonlinear behavior using surrogate data method. The values of D2 in respiratory
      movement during inhaling CO2-mixed gas (1.77 +/- 0.17) were significantly smaller
      than those during inhaling air (2.52 +/- 0.60) (P < 0.05). This might be related
      to a prompt change in the nonlinear signal from the central respiratory chemical
      system.

PMID- 14572688
TI  - Artificial myocardium with an artificial baroreflex system using nano technology.
AB  - Where is the place which should be helped in a patient with congestive heart
      failure? The answer may be contraction of the heart. At Tohoku University,
      development research of "the artificial myocardium" has been conducted, using a
      ball screw type electromagnetic motor. Furthermore, super-miniaturization is
      being attempted at present. Thus, a system with shape memory alloy is being
      developed. The cooling speed problem was solved by the application of the Peltier
      element. A drive at a speed equal to that of a heartbeat was realized by the
      application of this system. At present, a ventricular assist device is used for
      patients waiting for a heart transplant in Japan. An air driven type system
      disturbs a patient's QOL remarkably because it is connected to the drive device.
      With our concept, energy is provided by using the electromagnetic force from
      outside of the body by the use of transcutaneous energy transmission system.
      Magnetic shielding by amorphous fibers was used at Tohoku University to improve
      the total efficiency. A natural heart can alter the cardiac output corresponding
      to the demand. Artificial internal organs must participate in the system of the
      living body, too. Tohoku University has developed a resistance based artificial
      heart control algorithm, which simulated a baroreflex system to cope with every
      demand. Nano level sensing equipment is now under development at Tohoku
      University. At present, development is being conducted aiming at an "intelligent
      artificial myocardium".

PMID- 14572689
TI  - Chronoecoepidemiology of "strain": infradian chronomics of urinary cortisol and
      catecholamines during nightly exposure to noise.
AB  - This meta-analysis of published data (Noise Health 5 (2002) 35 and 47)
      summarizing a survey for 40 days of the nightly excretion of urinary free
      cortisol, epinephrine and norepinephrine validates a circaseptan cortisol pattern
      anticipated and reported earlier for cortisol, here not detected for the
      catecholamines. We also quantify a circadecan (about 10-day) variation in nightly
      norepinephrine excretion, but not in the excretion of the other two hormones
      examined. About 4.2-day variations, common to norepinephrine and epinephrine, and
      an about 4.7-day variation in cortisol await further scrutiny, since these
      components were not anticipated. Infradian characteristics are quantified time
      microscopically and differences among infradian aspects of the spectral element
      of endocrine chronomes (time structures; from chronos, time and nomos, rule) are
      demonstrated. Chronomics, the cartography of chronomes, reveals that "stress
      hormones" need to be examined separately in a budding chronoepidemiology seeking
      to detect how humans interact, mostly for better, sometimes for worse, with the
      undesirable features of the technology they create and of its consequences, such
      as aircraft noise.

PMID- 14572690
TI  - Stress/strain/life revisited. Quantification by blood pressure chronomics:
      benetensive, transtensive or maletensive chrono-vasculo-neuro-immuno-modulation.
AB  - We propose to initiate the automatic self-assessment of wear and tear as "stress
      and strain" by the time structures of blood pressure (BP) and heart rate (HR), in
      order to arrive eventually at an individualized timely and timed routine of life
      and to early preventive intervention as soon as needed. The routine may involve
      physiological scheduling of physical and mental activities and meals, and if need
      be of non-drug or drug treatment for stress amplification, e.g., by exercise,
      and/or strain (not stress) relief by relaxation. In so doing, we recognize the
      circulation as a pillar and marker of preventive and active neuroimmunomodulation
      (NIM), suggesting that some concerns of a vasculo- and broader NIM can be
      quantified by transdisciplinary chronobiology using its cartography--chronomics-
      of time structures, i.e., chronomes, from chronos = time and nomos = rule. Thus,
      we are introducing the chronomics of BP, HR and of other variables in the
      historical context of pioneers who were indispensable to experimental medicine.
      We build upon their contributions, but we must point out when, in the past, by
      necessity rather than choice, the giants provided rationalizing truisms that are
      no substitute for systematic serial data collection and appropriate computer
      analysis. A time-unspecified spotcheck as a baseline is much better than no
      measurement, but very often it is not enough, and it is always insufficient when
      an estimate of variability constitutes the information needed. For dynamic
      cycles, there are only reference cycles as a routine, although when maps are
      available, single timed spotchecks can be invaluable. With reference to their
      historical context, here we rely only upon data which necessity, rather than
      philosophy, compels us to collect.

PMID- 14572691
TI  - Clinical chronobiology and chronome-geriatrics at variance with recommendations
      of subsequent guidelines, yet focusing indeed on pre-hypertension in the
      physiological range.

PMID- 14572693
TI  - Background, problems, and perspectives of management of common pediatric skin
      problems in developing countries.

PMID- 14572694
TI  - Nutritional skin problems in children.

PMID- 14572695
TI  - Diagnosis of common, benign neonatal dermatoses.

PMID- 14572696
TI  - Enlightened therapy of the disorders of cornification.

PMID- 14572697
TI  - Management of mastocytosis.

PMID- 14572698
TI  - Management of epidermolysis bullosa in infants and children.

PMID- 14572699
TI  - Vitiligo and leukoderma in children.

PMID- 14572700
TI  - The treatment of hypopigmentation in children.

PMID- 14572701
TI  - Sun protection for children and adolescents.

PMID- 14572702
TI  - Pediatric cosmetic dermatology.

PMID- 14572703
TI  - Antihistamines and steroids in pediatric dermatology.

PMID- 14572704
TI  - Management of ichthyosis in infants and children.

PMID- 14572705
TI  - Environmental aspects of skin diseases in children: management of common
      problems.

PMID- 14572706
TI  - Who's the boss?

PMID- 14572712
TI  - Synthesis of mono- and di-hydroxylated prolines and 2-hydroxymethylpyrrolidines
      from non-carbohydrate precursors.
AB  - Natural and synthetic imino sugars are biologically important as glycosidase
      inhibitors. This review includes selected syntheses of 3-hydroxyproline, 4
      hydroxyproline, 3,4-dihydroxyproline, 2-hydroxymethyl-3-hydroxypyrrolidine and 2
      hydroxymethyl-pyrrolidine-3,4-diol, which exhibit glycosidase inhibitory and
      various other biological activities.

PMID- 14572713
TI  - Synthesis and structural characterization of 1-(D-glycosyloxy)phthalazines.
AB  - Coupling of the trimethylsilyl derivative of (2H)phthalazin-1-one with 1,2,3,4,6
      penta-O-acetyl-alpha-D-glucopyranose and 1,2,3,4,6-penta-O-acetyl-alpha-D
      galactopyranose in the presence of stannic chloride gave the respective
      glycosides, 2-(per-O-acetyl-D-glycosyloxy)phthalazines, which upon deacetylation
      gave the respective unprotected analogues. Under the same conditions 1,2,3,5
      tetra-O-acetyl-beta-D-ribofuranose gave 1-(2,3,5-tri-O-acetyl-alpha-D
      ribofuranosyloxy)phthalazine. Electrospray mass spectrometry aided the structural
      characterization of this series of 1-(D-glycosylyloxy)phthalazines. Low energy
      collisionally-induced dissociation tandem mass spectrometry of the protonated
      molecules confirmed the MS fragmentation routes and the structural identities of
      this novel series of glycosides.

PMID- 14572714
TI  - A novel synthesis of acyclonucleosides via allylation of 3-[1-(phenylhydrazono)-L
      threo-2,3,4-trihydroxybut-1-yl]quinoxalin-2(1H)one.
AB  - The allylation of 3-[1-(phenylhydrazono)-L-threo-2,3,4-trihydroxybut-1
      yl]quinoxalin-2(1H)one (1) gave, in addition to the anticipated 1-N-allyl
      derivative (2), a dehydrative cyclized product, 1-N-allyl-3-[5-(hydroxymethyl)-1
      phenylpyrazol-3-yl]quinoxalin-2-one (4) and its isomeric O-allyl derivative 3.
      The O-allyl group in 3 underwent acetolysis under acetylation conditions, in
      addition to the acetylation of the hydroxyl group, to afford 2-acetoxy-3-[5
      (acetoxymethyl)-1-phenylpyrazol-3-yl]quinoxaline (8) instead of the O-acetyl
      derivative of 3. Allylation of the tri-O-acetyl derivative of 1 caused the
      elimination of a molecule of acetic acid in addition to N-allylation to give 1-N
      allyl-3-[3,4-di-O-acetyl-2-deoxy-1-(phenylhydrazono)but-2-en-1-yl]quinoxalin-2
      one (11). Hydroxylation of the allyl group gave a glycerol-1-yl acyclonucleoside
      which can be alternatively obtained by a displacement reaction of the tosyloxy
      group in 2,3-O-isopropylidene-1-O-(p-tolylsulfonyl)glycerol (14), followed by
      deisopropylidenation. 1-N-(2,3-Dibromopropyl)-3-[5-(hydroxymethyl)-1-(4
      bromophenyl)pyrazol-3-yl]quinoxalin-2-one (15) underwent azidolysis to give a 2,3
      diazido derivative. The assigned structures were based on spectral analysis. The
      activity of compounds 2, 4, 6, and 15 against hepatitis B virus was studied.

PMID- 14572715
TI  - Electrospray tandem mass-spectrometric analysis of diastereo- and stereoisomeric
      pyrimidine nucleoside analogues based on the 1,3-dihydrobenzo[c]furan core.
AB  - Electrospray mass spectrometry and tandem mass spectrometry have aided the
      structural characterization of the diastereoisomeric cis- and trans-1-(3
      benzoyloxymethyl-1,3-dihydrobenzo[c]furan-1-yl)thymines and the four
      enantiomerically pure stereoisomers of uracil analogues. Low-energy collision
      induced dissociation MS/MS analysis of the various precursor molecular and
      cluster ions confirmed the characteristic fingerprint pattern obtained in the
      conventional electrospray spectra and allowed a convenient method for the
      characterization of novel 1,3-dihydrobenzo[c]furan nucleosides.

PMID- 14572716
TI  - Characterization of the alginates from algae harvested at the Egyptian Red Sea
      coast.
AB  - The alginates from five species of brown algae from the Egyptian Red Sea coast,
      namely: Cystoseira trinode, Cystoseira myrica, Sargassum dentifolium, Sargassum
      asperifolium, and Sargassum latifolium, were isolated and their compositions and
      structures studied by 1H NMR spectroscopy. All the alginates studied contain more
      guluronic acid (G) than mannuronic acid (M) and have a homopolymeric block-type
      structure (eta<1). The intrinsic viscosity of the alginate samples range from 8.6
      to 15.2 and the gel strength ranges from 10.97 to 15.51. The constitutional G-
      and M-blocks of alginates from two different species (C. trinode and S.
      latifolium) were separated after partial acid hydrolysis. The 1H NMR spectral
      data of the blocks GG and MM obtained by chemical fractionation were compared
      with those of polymeric alginates. The monomeric uronic acids were separated by
      complete acid hydrolysis of S. asperifolium alginate and the G and M monomers
      were characterized by 1H, 13C NMR spectroscopy as well as by paper
      electrophoresis.

PMID- 14572717
TI  - Acetylated methyl glucopyranuronate trichloroacetimidate as a glycosyl donor for
      efficient synthesis of disaccharides.
AB  - Allyl (methyl 2,3,4-tri-O-acetyl-beta-D-glucopyranosyl uronate)-(1-->3)-4,6-O
      benzylidene-2-deoxy-2-phthalimido-beta-D-glucopyranoside (4) and benzyl (methyl
      2,3,4-tri-O-acetyl-beta-D-glucopyranosyl uronate)-(1-->3)-4,6-O-benzylidene-2
      deoxy-2-phthalimido-beta-D-glucopyranoside (5) have been efficiently synthesized
      by coupling allyl 4,6-O-benzylidene-2-deoxy-2-phthalimido-beta-D-glucopyranoside
      (2) or benzyl 4,6-O-benzylidene-2-deoxy-2-phthalimido-beta-D-glucopyranoside (3)
      with methyl (2,3,4-tri-O-acetyl-1-O-trichloroacetimidoyl)-alpha-D
      glucopyranuronate (1), respectively, using trimethylsilyl triflate as promoter.

PMID- 14572718
TI  - Sugar hydrazone-metal complexes: transition- and non-transition metal complexes
      of monosaccharide S-alkylhydrazonecarbodithioates and dehydro-L-ascorbic acid
      bis(S-alkylhydrazonecarbodithioates).
AB  - Copper(II), nickel(II) and palladium(II) complexes with aldehydo-D-arabinose-, L
      arabinose-, D-galactose-, D-glucose- and D-mannose- S-methyl- and S
      benzylhydrazonecarbodithioates were synthesized and characterized by elemental
      analyses, infrared and UV-Vis. In these complexes the aldehydo sugar hydrazone
      acts as a mononegative NS bidentate ligand. The reaction of Cu(II) chloride,
      however, proceeded with reduction, and copper(I) complexes were isolated. The
      hydrazone molecule in these Cu(I) complexes acts as neutral NS bidentate ligand.
      Dehydro-L-ascorbic acid bis(S-methylhydrazinecarbodithioate) and
      bis(hydrazinecarbothioamide), as well as their corresponding Cu(II), Ni(II),
      zinc(II) and Pd(II) complexes were prepared and characterized. Electrospray (ES)
      and field desorption (FD) mass spectra suggest that the Cu(II), Ni(II), and
      Pd(II) complexes are monomeric (square planar), whereas the Zn(II) are dimeric
      and pentacoordinate.

PMID- 14572719
TI  - Convenient preparation of L-arabino-hexos-5-ulose derivatives from lactose.
AB  - 2,6-di-O-benzyl- (9), 2-O-benzyl-3,4-O-isopropylidene- (19), and 2-O-benzyl-6-O-m
      chlorobenzoyl-L-arabino-hexos-5-ulose (20) have been prepared using 4'-deoxy-4'
      eno- and 6'-deoxy-5'-eno lactose dimethyl acetal derivatives 7 and 14 as key
      intermediates. The synthesis of enol ethers 7 and 14 has been performed with good
      yields by base-promoted elimination of acetone or p-toluenesulfonic acid from
      2',6'-di-O-benzyl-, and 6'-O-p-toluenesulfonyl-2,3:5,6:3',4'-tri-O
      isopropylidenelactose dimethyl acetal, respectively. The epoxidation with MCPBA
      of 7 and 14 in methanol or dichloromethane furnishes C-5'-methoxy and C-5'-m
      chlorobenzoyloxy derivatives, easily transformed with good yields into L-arabino
      5-ketoaldohexoses 9, 19 and 20.

PMID- 14572720
TI  - Synthesis of beta-D-glucose oligosaccharides from Phytophthora parasitica.
AB  - The glucohexaose, beta-D-Glcp-(1-->3)-[beta-D-Glcp-(1-->3)-beta-D-Glcp-(1-->3)
      beta-D-Glcp-(1-->6)]-beta-D-Glcp-(1-->3)-D-Glcp, was synthesized as its allyl
      glycoside via 3+3 strategy. The trisaccharide donor, 2,3,4,6-tetra-O-benzoyl-beta
      D-glucopyranosyl-(1-->3)-2,4,6-tri-O-acetyl-beta-D-glucopyranosyl-(1-->3)-2,4,6
      tri-O-acetyl-alpha-D-glucopyranosyl trichloroacetimidate (11), was obtained by 3
      selective coupling of isopropyl 4,6-O-benzylidene-1-thio-beta-D-glucopyranoside
      (2) with 2,3,4,6-tetra-O-benzoyl-beta-D-glucopyranosyl-(1-->3)-2-O-acetyl-4,6-O
      benzylidene-alpha-D-glucopyranosyl trichloroacetimidate (6), followed by
      hydrolysis, acetylation, dethiolation, and trichloroacetimidation. Meanwhile, the
      trisaccharide acceptor, allyl 2,3,4,6-tetra-O-benzoyl-beta-D-glucopyranosyl-(1-
      >3)-2-O-acetyl-beta-D-glucopyranosyl-(1-->3)-4,6-di-O-acetyl-2-O-benzoyl-alpha-D
      glucopyranoside (14), was prepared by coupling of allyl 4,6-di-O-acetyl-2-O
      benzoyl-alpha-D-glucopyranoside (12) with 6, followed by debenzylidenation.
      Condensation of 14 with 11, followed by deacylation, gave the target hexaoside. A
      beta-(1-->3)-linked tetrasaccharide 29 was also synthesized with methyl 2-O
      benzoyl-4,6-O-benzylidene-beta-D-glucopyranosyl-(1-->3)-2,4,6-tri-O-acetyl-beta-D
      glucopyranoside (25) as the acceptor and acylated beta-(1-->3)-linked
      disaccharide 21 as the donor.

PMID- 14572721
TI  - Oxidation and metal-ion affinities of a novel cyclic tetrasaccharide.
AB  - The cyclic tetrasaccharide, cyclo-(-->6)-alpha-D-Glcp-(1-->3)-alpha-D-Glcp-(1-
      >6)-alpha-D-Glcp-(1-->3)-alpha-D-Glcp-(1-->), was oxidized in high yield to a
      dicarboxylic acid, cyclo-(-->6)-alpha-D-Glcp-(1-->3)-alpha-D-GlcpA-(1-->6)-alpha
      D-Glcp-(1-->3)-alpha-D-GlcpA-(1-->). The parent and oxidized compound were then
      screened for the ability to form stable complexes with 20 metal cations. Ion
      exchange thin-layer chromatography was utilized to survey binding in aqueous and
      50% methanolic solutions. The screening identified Pb2+, Fe2+ and Fe3+ as forming
      strong metal chelates with the oxidized cyclic tetrasaccharide. The stoichiometry
      of the oxidized cyclic tetrasaccharide and Pb2+ complex was determined to be 1:1
      using aqueous gel-permeation chromatography. Perturbations between the free and
      complexed structure were examined using NMR spectroscopy. Molecular simulations
      were used to identify a probable structure of oxidized cyclic tetrasaccharide
      complexed with Pb2+.

PMID- 14572722
TI  - Synthesis of amino-substituted hexo- and heptopyranoses from D-galactose.
AB  - After condensation of D-galactose with two equivalents of acetone, the last free
      hydroxy group was transformed into an acylated amino group by Swern oxidation,
      oxime formation, LiAlH4 reduction and acylation. The intermediate aldehyde was
      homologated with the Wittig reagent, (methoxymethyl)triphenylphosphonium
      chloride, to afford, after careful hydrolysis, a homologous heptodialdo-1,5
      pyranose. Condensation of the aldehyde with hydroxylamine and subsequent LiAlH4
      reduction provided a bis-O,O-isopropylidene-protected 7-amino-6,7
      dideoxygalactoheptopyranose, which was acylated with various carboxylic acid
      derivatives. The isopropylidene protective groups were cleaved by careful
      hydrolysis or alcoholysis to yield 6-acylamino-6-deoxy-galactopyranoses and 7
      acylamino-6,7-dideoxy-galactohepto-pyranoses.

PMID- 14572723
TI  - Structure of the O-polysaccharide of Proteus mirabilis O38 containing 2
      acetamidoethyl phosphate and N-linked D-aspartic acid.
AB  - The O-antigen of Proteus mirabilis O38 was found to be unique among bacterial
      polysaccharides and to have the following structure: [carbohydrate structure in
      text] where D-Qui4N(Ac-D-Asp) is 4-(N-acetyl-D-aspart-4-ylamino)-4,6-dideoxy-D
      glucose and AcEtnP is 2-acetamidoethyl phosphate. Neither of these entities have
      been hitherto found in natural polysaccharides. Structural studies were performed
      using 1D and 2D NMR spectroscopy, including experiments run in an H2O/D2O mixture
      to reveal correlations for NH protons. In addition, dephosphorylation, carboxyl
      reduction and selective cleavages were applied. Solvolysis of the polysaccharide
      with anhydrous HF gave an alpha-D-GlcNAc-(1-->3)-D-Qui4N(Ac-D-Asp) disaccharide.
      Solvolysis with trifluoromethanesulfonic (triflic) acid afforded D
      GlcNAc6(AcEtnP), thus showing the suitability of this reagent for the preparation
      of phosphorylated sugar derivatives.

PMID- 14572724
TI  - Structure and potential immunological activity of a pectin from Centella asiatica
      (L.) Urban.
AB  - S3A was a RG-I pectin isolated from Centella asiatica that contained Rha, Ara,
      Gal, Glc and GalA in molar ratio of 1.0:0.6:1.5:0.2:1.1 and had been found to
      have a backbone composed mainly of the disaccharide repeat unit, -->4)-alpha-D
      GalpA-(1-->2)-alpha-L-Rhap-(1-->. Based on methylation analysis, NaIO4 oxidation,
      partial acid hydrolysis and lithium-treatment, the structural features were
      elucidated. Side chains of S3A were predominantly linked to O-4 of 1,2,4-linked
      alpha-L-Rhap. The side chains are comprised of arabinosyl chains, galactosyl
      chains, arabinogalactosyl chains and short glucosyl chains. A total of 45% Rhap
      in the backbone was substituted by side chains. The arabinosyl residues were
      mostly distributed in the arabinosyl side chains. According to the immunological
      results of S3A and its degraded derivatives, S3A had no immunological activity,
      but its derivatives had immuno-stimulating activities to some extent.

PMID- 14572725
TI  - Physical investigations of surface membrane-water relationship of intact and
      gelatinized wheat-starch systems.
AB  - Water mobility in intact and dried gelatinized starch was investigated by
      gravimetric water sorption, scanning electron microscopy (SEM), and solid-state
      nuclear magnetic resonance (NMR). A multi-component exponential model
      quantitatively measured different spin-spin relaxation times of two water
      components, namely bound water (Tsi) at 3.16 ms and mobile or free water (Tsii)
      at 3.23 ms, as a function of water activity (aw). The starch samples were
      moistened to 30% moisture content. SEM confirmed the disrupted, absorbent
      microstructure in dried, gelatinized starch powder and revealed starch granules
      in an incomplete gelatinized state, as compared to the complete membrane surface
      of the intact starch granule. Starch granules sorbed significantly differently at
      low aw, but after aw=0.44, sorption leveled similarly with increasing aw. The
      presence and role of a surface membrane was concluded, in support of the
      hypothetical "water sink" properties of intact granules, and was considered to
      influence in part the sorption behavior of incompletely gelatinized starch
      granules.

PMID- 14572726
TI  - High yield regioselective monobenzyloxycarbonylation of secondary alcohols in
      glycopyranoside series.
AB  - The regioselective monobenzyloxycarbonylation of secondary alcohols in methyl 6-O
      (4-methoxytrityl)-alpha-D-manno-, gluco- and galactopyranoside has been achieved
      in high yields (74-85%) by using benzyl chloroformate in the presence of 4
      dimethylaminopyridine and/or 1,4-diazabicyclo[2.2.2]octane.

PMID- 14572727
TI  - Crystal structure and chirality of natural floridoside.
AB  - The crystal structure and absolute configuration of natural floridoside (2-O
      alpha-D-galactopyranosylglycerol) were determined by single-crystal X-ray
      diffraction analysis. The space group is orthorhombic P2(1)2(1)2(1) with Z=4,
      a=4.885(1), b=9.734(1), c=23.886(2) A at 296 +/- 2 K. The structure was solved by
      a direct method and refined to R=0.0351 from 1914 reflections of Cu Kalpha
      radiation.

PMID- 14572728
TI  - An efficient preparation of 6(I,IV) dihydroxy permethylated beta-cyclodextrin.
AB  - We report on a straightforward synthesis of 2(I-VII),3(I-VII),6(II,III,V-VII)
      nonadeca-O-methylcyclomaltoheptaose, a methylated beta-cyclodextrin derivative
      bearing two 6(I,IV) hydroxyl groups, from its easily available benzylated
      counterpart.

PMID- 14572729
TI  - Celebrities needed to promote brain research in Europe?

PMID- 14572730
TI  - The sinister side of Italian soccer.

PMID- 14572731
TI  - HBPP and the pursuit of standardisation.

PMID- 14572732
TI  - Cholinesterase inhibitors for vascular dementia?

PMID- 14572734
TI  - Hemiballism: revisiting a classic disorder.
AB  - Hemiballism is a rare movement disorder that presents with unilateral flinging
      movements of the limbs. In traditional teaching, it has been characterised as
      almost pathognomonic of a lesion in the subthalamic nucleus (STN). The prognosis
      was described as grave, with severe disability and death in many cases. However,
      review of more recent reports shows that the STN is directly involved in only a
      minority of cases. The prognosis is benign in most cases, with almost all
      patients responding well to treatment and many having spontaneous remission,
      although long-term prognosis of cerebrovascular disease may not be so good. There
      have also been recent insights into the pathophysiology of hemiballism, which
      have emphasised the importance of altered firing patterns in basal-ganglia
      structures. Recent studies have pointed to previously unrecognised causes,
      particularly non-ketotic hyperosmolar hyperglycaemia and complications of HIV
      infection, that may account for a substantial proportion of cases of hemiballism.

PMID- 14572735
TI  - Dysautonomia in Parkinson's disease: neurocardiological abnormalities.
AB  - Symptoms of abnormal autonomic-nervous-system function occur commonly in
      Parkinson's disease (PD). Orthostatic hypotension in patients with parkinsonism
      has been thought to be a side-effect of treatment with levodopa, a late stage in
      the disease progression, or, if prominent and early with respect to disordered
      movement, an indication of a different disease, such as multiple system atrophy.
      Instead, patients with PD and orthostatic hypotension have clear evidence for
      baroreflex failure and loss of sympathetic innervation, most noticeably in the
      heart. By contrast, patients with multiple system atrophy, which is difficult to
      distinguish clinically from PD, have intact cardiac sympathetic innervation. Post
      mortem studies confirm this distinction. Because PD involves postganglionic
      sympathetic noradrenergic lesions, the disease seems to be not only a movement
      disorder with dopamine loss in the nigrostriatal system of the brain, but also a
      dysautonomia, with norepinephrine loss in the sympathetic nervous system of the
      heart.

PMID- 14572736
TI  - Pain processing in dementia and its relation to neuropathology.
AB  - Most clinical studies of pain in dementia have focused on assessment procedures
      that are sensitive to pain in "demented" or "cognitively impaired" elderly
      patients. The neuropathology of dementia has not played a major part in pain
      assessment. In this review, the neuropathological effects of dementia on the
      medial and the lateral pain systems are discussed. We focus on Alzheimer's
      disease (AD), vascular dementia, and frontotemporal dementia. Lewy-body disease
      and Creutzfeldt-Jakob disease are briefly reviewed. The results of the studies
      reviewed show that, although the subtypes of dementia show common
      neuropathological features (such as atrophy and white-matter lesions), the degree
      by which they occur and affect pain-related areas determine the pattern of
      changes in pain experience. More specifically, in AD and even more so in
      frontotemporal dementia, a decrease in the motivational and affective components
      of pain is generally present whereas vascular dementia might be characterised by
      an increase in affective pain experience. Future studies should combine data from
      experimental pain studies and neuropathological information for pain assessment
      in dementia.

PMID- 14572737
TI  - Complex regional pain syndrome: mystery explained?
AB  - Complex regional pain syndrome (CRPS) is the result of changes to the
      somatosensory systems that process noxious, tactile, and thermal information; to
      the sympathetic systems that innervate skin (blood vessels, sweat glands); and to
      the somatomotor systems. The changes suggest that the CNS representations of the
      systems have been altered. Patients with CRPS also have peripheral changes (eg,
      oedema, signs of inflammation, sympathetic-afferent coupling [the basis for
      sympathetically maintained pain], and trophic changes) that cannot be explained
      by central changes. On the basis of clinical observation and research in human
      beings and animals, we hypothesise that CRPS is a systemic disease involving the
      CNS and peripheral nervous system. The most important question for future
      research is what causes CRPS? In this article, we suggest a change to the focus
      of research efforts and treatment. We also suggest there be diagnostic
      reclassification and redefinition of CRPS.

PMID- 14572738
TI  - Management of acute ischaemic stroke: new guidelines from the American Stroke
      Association and European Stroke Initiative.
AB  - BACKGROUND: Ischaemic stroke is an important cause of death and dependency in
      industrialised countries; it has a high incidence (affecting up to 0.2% of the
      population each year) and is commonly lethal or disabling. One in six patients
      die in the first month after ischaemic stroke, and half of survivors are
      permanently disabled despite best efforts to rehabilitate them and to prevent
      complications, recurrent stroke, and other serious vascular events. Optimisation
      of the early, and ongoing, management of patients with acute ischaemic stroke is
      pivotal to the reduction of both case fatality and long-term disability. RECENT
      DEVELOPMENTS: Guidelines for the early management of patients with ischaemic
      stroke have recently been published by the Stroke Council of the American Stroke
      Association (ASA; Adams and co-workers, Stroke 2003; 34: 1056-83) and the
      European Stroke Initiative (EUSI; European Stroke Initiative Executive Committee
      and Writing Committee, Cerebrovasc Dis 2003; 16: 311-38). Although transatlantic
      differences might create different interpretations, priorities, and views, the
      guidelines are remarkably similar, even regarding controversial issues. We
      believe this is not only because both groups have had the opportunity to discuss
      many of the controversial issues at international meetings, but also because both
      groups have endorsed the concept of evidence-based medicine and have based their
      recommendations on similar classifications of the levels of evidence for the
      effectiveness of interventions. This is a triumph for evidence-based medicine and
      a major step towards unification of acute stroke management worldwide. WHERE
      NEXT?: There are three main challenges in stroke management. To increase the body
      of reliable evidence from large randomised controlled trials (RCTs) of the
      safety, effectiveness, and cost of promising treatments (eg, thrombolysis,
      antithrombotic therapy, neuroprotection, and interventional recanalisation, alone
      and in combination) in a wide range of patients around the world. To facilitate
      the widespread development of stroke units, delivery of organised stroke care,
      and emergency transport of patients with stroke to appropriate stroke centres.
      And finally, to improve the uptake of effective therapies into clinical practice
      (eg, by widely disseminating the ASA and EUSI guidelines).

PMID- 14572739
TI  - Research in the European Union.

PMID- 14572745
TI  - Bug's life.

PMID- 14572746
TI  - Intermittent maximal androgen blockade in patients with metastatic prostate
      cancer: an EORTC feasibility study.
AB  - OBJECTIVES: In preparation of an intercontinental Phase III trial comparing
      continuous maximal androgen blockade (MAB) to intermittent androgen suppression
      (IAS) in untreated metastatic prostate cancer, a feasibility study on IAS was
      accomplished. METHODS: 107 patients (median follow-up 92 weeks) were treated with
      MAB until a PSA nadir was reached. Nadir was defined as PSA below 20 ng/ml
      corresponding to PSA reduction by at least 80% of baseline value. Criteria for
      restarting treatment was PSA >20 ng/ml and PSA > nadir + 50%. Trials aim was to
      assess the likelihood that 80% of patients would reach a first nadir and that 80%
      of these would also reach a second nadir. RESULTS: 51.4% of patients had some
      degree of pain at entry, 27.1% had >15 hot spots, 23.7% demonstrated obstruction.
      Only 17.8% had normal potency, 56.1% were totally impotent. One to seven cycles
      of treatment were given. 76.6% of patients reached a 1st nadir after a median of
      19 weeks of treatment, 84.1% of these started the 2nd cycle and 71% of them
      reached a 2nd nadir after a median of 13.6 weeks. Median time off-treatment was
      14.3 and 16.0 weeks corresponding to 38.4% and 48.5% of the duration of each
      cycle. A similar proportion of patients was reported to be potent during follow
      up compared to baseline. 32.7% of patients died during follow-up, 82.9% of
      prostate cancer. CONCLUSION: Around 75% of the patients achieved a nadir at each
      cycle. The concept of IAS seems to be feasible and warrants further
      investigation.

PMID- 14572747
TI  - Immediate treatment with bicalutamide 150mg as adjuvant therapy significantly
      reduces the risk of PSA progression in early prostate cancer.
AB  - OBJECTIVE: To evaluate the effect of bicalutamide ('Casodex') 150mg (in addition
      to standard care), on the risk of prostate-specific antigen (PSA) progression, in
      patients with early prostate cancer. METHODS: The bicalutamide 150mg Early
      Prostate Cancer (EPC) programme is the largest clinical trial programme in the
      treatment of prostate cancer to date. This paper reports the PSA progression data
      from the EPC programme at a median of 3years' follow-up, for the overall study
      population, and across the radical prostatectomy and radiotherapy primary therapy
      strategies. PSA progression was predefined as the earliest occurrence of PSA
      doubling from baseline, objective progression, or death from any cause. RESULT:
      Overall, bicalutamide 150 mg in addition to standard care significantly reduced
      the risk of PSA progression by 59% compared with standard care alone (HR 0.41;
      95% CI 0.38, 0.45; p<<0.0001). Significant reductions were observed following
      radical prostatectomy (51%; HR 0.49; 95% CI 0.43, 0.56; p<<0.0001) and
      radiotherapy (58%; HR 0.42; 95% CI 0.33, 0.53; p<<0.0001). Further exploration of
      the data by disease stage, nodal status, Gleason score and pre-treatment PSA
      level revealed significant reductions in the risk of PSA progression across most
      prognostic risk factor subgroups. CONCLUSIONS: Bicalutamide 150mg significantly
      reduces the risk of PSA progression, irrespective of whether patients received
      radical prostatectomy or radiotherapy as standard care. The EPC programme is
      ongoing and further progression and survival data are awaited.

PMID- 14572748
TI  - Strontium(89) chloride versus palliative local field radiotherapy in patients
      with hormonal escaped prostate cancer: a phase III study of the European
      Organisation for Research and Treatment of Cancer, Genitourinary Group.
AB  - OBJECTIVES: To compare toxicity, subjective response rate, time to subjective
      progression and overall survival in patients with painful bone metastases of
      hormone-resistant prostate cancer (HRPC) treated with a single intravenous
      injection of 150MBq (4mCi) Strontium(89) Chloride (S) or palliative local field
      radiotherapy (R) with the usual radiotherapy regimen used at each centre. The
      costs of both treatments were also assessed. PATIENTS AND METHODS: 101 patients
      were randomized to S and 102 to R. Time to event endpoints were compared with the
      Logrank test and Kaplan-Meier curves, in the intent-to-treat population (2-sided
      alpha=0.05). RESULTS: Baseline characteristics of both groups were comparable.
      There was a borderline statistically significant difference in overall survival
      in favour of the local field radiotherapy (R: 11 months; S: 7.2 months;
      p=0.0457). There was no difference in progression-free survival or time to
      progression. Subjective response was seen in 34.7% in the S-arm and in 33.3% in
      the R-arm. A biochemical response was observed in 10% and 13% of the R- and S
      groups, respectively. There was no difference in treatment toxicity between the
      two groups. CONCLUSION: In symptomatic HRPC, pain treatment with local field
      radiotherapy is associated with a better overall survival compared to
      Strontium(89). The lower costs of local field radiotherapy also favour the use of
      this treatment in patients with HRPC. The reason for the apparent survival
      benefit of localised radiation treatment is not clear.

PMID- 14572749
TI  - Spinal cord compression in metastatic prostate cancer.
AB  - INTRODUCTION: Spinal cord compression (SCC) in metastatic prostate cancer is not
      rare occurring in 1 to 12% of patients. We have analysed patients treated for
      this condition in our institution assessing outcome and prognostic factors.
      MATERIAL AND METHODS: Retrospective analysis of the notes of 24 patients
      hospitalised with SCC due to metastatic prostate cancer from 1987 to 2001.
      RESULTS: At presentation 3 patients were ambulant with mild neurological deficit,
      12 patients were paraparetic and 9 patients were paraplegic. Diagnosis was
      established by emergency myelogram, CT-scan or MRI of the spine. 8 patients had
      received no hormone treatment prior to diagnosis of SCC. 19 patients presented
      dorsal or lumbar pain requiring opioid treatment on average 60 days before onset
      of neurological symptoms (range 10-840). All patients underwent steroid
      treatment; the 8 patients without prior hormone therapy were treated with
      bilateral orchidectomy, 1 out of these 8 patients had castration without other
      treatments; 12 patients underwent radiotherapy alone and 9 radiotherapy and
      laminectomy; 2 patients were in terminal conditions and receive only steroid
      treatment. Overall 15/24 patients were ambulant after treatment. 8 out of 9
      patients treated by laminectomy and radiotherapy were ambulant after treatment
      versus 7 out of 12 patients treated by radiotherapy alone.17 patients died during
      follow-up with a median survival of 4 months (2 weeks to 49 months). 7 patients
      were alive at the last control with a mean follow-up of 10 months (range 4-40).
      CONCLUSION: Outlook in patients with spinal cord compression from metastatic
      prostate cancer is poor. Efforts must be concentrated on prevention of spinal
      cord compression. Patients with hormone resistant prostate cancer who develop
      persistent back pain should undergo imaging studies (bone scan, spine CT-scan or
      MNR) and prophylactic local radiotherapy to the spine if bony metastases are
      identified.

PMID- 14572750
TI  - Methylation-specific PCR for DNA-based detection of occult tumor cells in lymph
      nodes of prostate cancer patients.
AB  - OBJECTIVES: To assess the feasibility of methylation-specific PCR (MSP) for the
      detection of promoter hypermethylation of the detoxifying glutathione-S
      transferase P1 gene (GSTP1) to detect occult prostate cancer cells in lymph nodes
      (LNs). METHODS: Paraffin-embedded pelvic LNs from 20 patients with pT2pN0M0R0
      prostate cancer who developed PSA relapse were assessed by MSP. In 18 of the
      patients, samples of the primary tumor were obtained for MSP. In 19 patients,
      bone marrow (BM) aspirates were analyzed preoperatively for disseminated tumor
      cells by immunocytochemistry (mAb A45-B/B3). In 16 patients, biopsies of the
      anastomotic region were performed following PSA relapse. As a negative control
      GSTP1 methylation status was also assessed in LNs from 9 patients for whom an
      autopsy was performed for non-cancer-related causes. RESULTS: All primary tumors
      displayed GSTP1 hypermethylation (HM). Preoperative BM assessment showed
      disseminated tumor cells in 8/20 cases (40%). In 4 patients, biopsies of the
      vesico-urethral anastomosis showed local tumor recurrence. The LNs in the cancer
      patients showed GSTP1 HM in 18/20 cases (90%) versus 1/9 patients (11.1%) in the
      non-cancer cohort (p<0.0001). CONCLUSION: GSTP1 HM appears to be well suited for
      molecular staging of prostate cancer and accurately detects disseminated tumor
      cells in LNs, which was seen in 90% of the patients with PSA relapse. However,
      the limited number of patients and the finding of benign and malignant prostatic
      tissue at the vesico-urethral anastomosis as a putative local source of PSA
      recurrence does not allow us to draw conclusions on the prognostic significance
      of our findings, yet.

PMID- 14572751
TI  - Treatment strategies, patterns of drug use and treatment discontinuation in men
      with LUTS suggestive of benign prostatic hyperplasia: the Triumph project.
AB  - OBJECTIVES: We aimed to describe treatment strategies for lower urinary tract
      symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH), adherence to and
      persistence with pharmacological treatment and the association between the type
      of LUTS/BPH complaints and early treatment discontinuation. METHODS: Within a
      large GP database (IPCI) in the Netherlands we identified all males > or =45
      years newly diagnosed with LUTS/BPH during 1995-2000. Details on treatment were
      assessed from the electronic patient records. Logistic regression analysis was
      used to estimate the association between the type of main urinary complaints and
      early treatment discontinuation. RESULTS: Of the 2214 men with incident LUTS/BPH,
      1075 received pharmacological treatment and 238 underwent prostate surgery. The
      average adherence differed slightly between drugs: 67% for alpha-blockers, 73%
      for 5alpha-reductase inhibitors and 71% for combination therapy. 26% of the
      treated patients discontinued treatment early. The probability of early
      discontinuation was higher if patients mainly expressed one type of complaint:
      voiding (OR(adj) 3.38; 95%CI: 1.89-6.04), post micturition (OR(adj) 2.37; 95%CI:
      1.15-4.87) or storage symptoms (OR(adj) 1.85; 95%CI: 1.16-2.95) as compared to
      patients expressing a combination of symptoms. The risk of early discontinuation
      was higher if patients had a normal PSA measurement. Older age and a higher
      chronic disease score protected against early treatment discontinuation.
      CONCLUSIONS: Almost half of newly diagnosed LUTS/BPH patients are
      pharmacologically treated, and a quarter discontinues very rapidly. Stopping
      early is more frequent among younger persons, persons with only one type of main
      urinary complaint, no other co-morbidity and a normal PSA.

PMID- 14572752
TI  - Impact of prostatitis NIH IIIB (prostatodynia) on ejaculate parameters.
AB  - OBJECTIVES: Prostatitis NIH IIIB is defined by chronic pelvic pain without
      evidence of inflammation in prostate secretions or ejaculate. The relations
      between chronic prostatitis and fertility are discussed controversially. In this
      context, we analysed fertility data of a well defined collective of patients with
      prostatitis NIH IIIB. METHODS: We analysed prospective fertility data of a group
      of 30 patients with chronic prostatitis NIH IIIB and compared these data with the
      duration of symptoms as well as with an age-matched control group. RESULTS: The
      prostatitis group and the control group differed significantly in terms of
      ejaculate volume, motility and fructose concentration. The remaining parameters
      did not differ significantly. An azoospermia was present in 3 patients of the
      prostatitis group versus none of the control group. The duration of symptoms did
      not correlate with the sperm parameters (sperm density, motility and morphology).
      CONCLUSIONS: Patients with prostatitis NIH IIIB have changes in their ejaculate
      with a reduction of motility and a reduced fructose concentration. This supports
      a somatic aetiology of the chronic pelvic pain syndrome.

PMID- 14572753
TI  - BPH and inflammation: pharmacological effects of Permixon on histological and
      molecular inflammatory markers. Results of a double blind pilot clinical assay.
AB  - INTRODUCTION: The role of infiltrating cells (I.C.), commonly observed in the
      adenoma interstitial tissue, is unknown. We tested the hypothesis that I.C. are
      related with BPH progression by: phenotypically characterising these cells;
      quantifying the expression of lymphokines and growth factors; investigating the
      response to Permixon (P) in a clinical study. Permixon is a lipido sterolic
      extract of Serenoa repens possessing pharmacological activities and widely used
      in the treatment of men with BPH. MATERIAL AND METHODS: A multicenter open pilot
      study of two parallel groups on BPH patients was carried out. They were
      randomized to receive either oral Permixon (P) 160 mg bid for three months or to
      be followed for 3 weeks without any treatment before surgery (control group C).
      Strict inclusion and exclusion criteria were applied to conform homogeneous
      groups, avoiding interferences of inflammatory drugs or others. Baseline clinical
      profile was almost identical in both groups in terms of age (65.7+/-5.1 vs.
      67.1+/-5.8 years), IPSS (19.8+/-6.1 vs. 19.0+/-5.8), prostate volume (64.8+/-18.9
      vs. 71.5+/-29.3cc), Q(max) (9.6+/-3.2 vs. 10.6+/-2.6 ml/s), and Q(L) (4.0+/-1.1
      vs. 3.5+/-0.7). Surgery was ultimately performed on 29 patients (17C, 12P) by
      TURP or retropubic adenomectomy. Adenoma samples were routinely stained with HE
      and later prepared for immunohistochemical studies using CD3, CD20 and CD68
      antibodies. Counting of positives cells, lymphoid aggregates and foci were done
      using EnVision technique and the Tech Mate processor. Cytokines, growth factors
      and eicosanoids were determined by Elisa kits following the manufactured
      recommendation. RESULTS: HISTOLOGICAL: A difference was observed in the number of
      lymphocytes B between C (91.4+/-44.1) and P treated (58.2+/-53.7) groups
      (p=0.097). BIOLOGICAL MARKERS: TNFalpha and IL-1beta were dramatically lower in
      the Permixon treated group. Other parameters did not show significant changes.
      CLINICAL: IPSS in the Permixon treated group was significantly reduced (p<0.006)
      from 20.0+5.9 to 14.9+3.8 after three months of treatment. COMMENTS: The BPH
      inflammatory hypothesis was tested in humans. Our pilot study shows a significant
      reduction of some inflammatory parameters in prostatic tissues of patients
      treated with Permixon. These biological findings justify a pharmacological effect
      of this drug on the inflammatory status of the adenoma. A correlation with
      clinical improvement was observed.

PMID- 14572754
TI  - Localization of avidin in superficial bladder cancer: a potentially new approach
      for radionuclide therapy.
AB  - OBJECTIVE: To verify whether native avidin, made radioactive through the binding
      with technetium-99m labeled biotin (99mTc-biotin), selectively accumulated in
      superficial tumor tissues following intravesical administration. METHODOLOGY: A
      total of fifteen patients with transitional cell bladder cancer were instilled
      intravesically with radiolabeled avidin. Cold biopsies were obtained from
      macroscopically normal and tumor tissues before transurethral resection (TUR) and
      the radioactivity in the samples was measured. RESULTS: Increased accumulation of
      radiolabeled avidin was observed in tumor tissue compared to normal bladder
      tissue and in some cases, remarkably high quotients of uptake (q) in tumor versus
      normal tissues were determined (86 and 44). The three patients instilled with a
      deglycosylated avidin at neutral pI, who served as a control, showed no
      significant uptake in either tumor or normal urothelium and no difference in
      relative uptake (q=1.0). CONCLUSION: This pilot study indicated that intravesical
      administration of radiolabeled avidin resulted in a preferential accumulation in
      tumor tissue compared to normal urothelium. The instillation of radiolabeled
      avidin warrant further investigations in order to explore the possibility to
      treat superficial bladder neoplasms locally by replacing 99mTc with high energy
      beta emitting radionuclides associated with biotin.

PMID- 14572755
TI  - Increased expression of matrix metalloproteinase 9 correlates with poor
      prognostic variables in renal cell carcinoma.
AB  - BACKGROUND: MMP2 and MMP9 are two gelatinolytic enzymes, which are key regulators
      of tumor invasion and metastasis. This study aimed to clarify the prognostic
      significance of MMP2 and MMP9 with particular regard to their transcript levels,
      enzymatic activities in renal cell carcinomas (RCCs). MATERIALS AND METHODS:
      Through cDNA array, the differential expression of the MMP superfamily was
      evaluated in RCC. Various properties of MMP2 and MMP9 were quantified, in 178
      patients with RCC, based on the Heidelberg classification. Of these, 145 cases
      including 16 fresh-frozen cases were available for MMP2 and MMP9 transcript level
      evaluation. In addition, gelatinolytic activity was assessed by zymography in 16
      other fresh-frozen samples from new RCC cases. RESULTS: MMP2, 9, 11, 14, and 16
      were upregulated in the conventional RCC in comparison with the chromophobe RCC,
      whereas MMP1, 11 and 16 were pronounced in papillary RCC. MMP9 transcript levels
      were strongly associated with the MMP9 enzymatic activity (p=0.001), and
      therefore, with disease-free survival (p=0.001) and metastasis (p=0.011).
      Gelatinolytic activity of MMP9 by zymography was strongly associated with MMP9
      mRNA expression, which was more intense in 'conventional' RCC than in
      'chromophobe' RCC (p=0.001), irrespective of tumor grade or stage. MMP9 was
      proven to be a significant prognostic predictor by multi-variate survival
      analysis (p=0.0054). MMP2 enzymatic activity disappeared in spite of its constant
      transcript expression in RCC. CONCLUSIONS: MMP9 appears to be regulated at the
      transcript level, whereas MMP2 is regulated at the posttranscriptional level.
      Poor survival with a high frequency of metastases in 'conventional' RCC is
      associated with MMP9, which exhibits a high transcriptional level, and a high
      gelatinolytic activity. As a result, MMP9 may be a candidate of predictors of
      disease-free survival in RCC.

PMID- 14572756
TI  - Laparoscopic nerve- and seminal-sparing cystectomy with orthotopic ileal
      neobladder: the first three cases.
AB  - INTRODUCTION AND OBJECTIVES: Seminal and prostate sparing cystectomy represents
      an alternative in young patients where preservation of urinary continence and
      sexual potency are fundamental. We present our preliminary experience with this
      procedure performed laparoscopically. METHODS: Three men-53, 58 and 49 years old
      suffering from recurrent superficial transitional cell carcinoma of the bladder,
      resistant to intravesical therapy, underwent laparoscopic nerve, prostate and
      seminal vesical sparing cystectomy. One week before surgery, TURP was performed
      to create an adequate prostate capsule. After pneumoperitoneum induction and the
      positioning of five/six trocars, the ureters were clipped and transected, the vas
      deferens and seminal vescicles were identified and prepared for the conservative
      procedure. Cystectomy was performed with vascular pedicles transection by
      EndoGia. The reconstruction of the bladder was obtained through a 7 cm
      longitudinal periumbilical incision using 60 cm of ileus and an orthotopic
      neobladder realized outside the abdomen. The ileocapsular anastomosis was
      performed laparoscopically after the re-induction of pneumoperitoneum. RESULTS:
      No major complications were recorded. The surgical time was respectively 480, 450
      and 410 min. Blood loss was 150, 220 and 300 ml respectively. Drains were removed
      after 4 days (two patients) and 6 days (one patient) and the patients were
      discharged after 8 days (two patients) and 9 days. The patients were fully
      continent after catheter removal with normal uroflowmetry. At the three month
      follow-up they had a normal sexual function, equivalent to the preoperative
      assessment. The patients reported adequate erections for intercourse.
      CONCLUSIONS: Laparoscopic prostate and seminal cystectomy with orthotopic ileal
      neobladder is a safe, feasible, reproducible surgical technique. In patients who
      desire to preserve sexual functioning and obtain complete continence it
      represents a valid alternative to classic radical cystectomy.

PMID- 14572757
TI  - Systematic review: efficacy of silicone microimplants (Macroplastique) therapy
      for stress urinary incontinence in adult women.
AB  - OBJECTIVE: To assess the efficacy of silicone microimplants (Macroplastique;
      polydimethylsiloxane) therapy for stress urinary incontinence in adult women,
      using a systematic review of identified studies. MATERIALS AND METHODS: A
      computer-aided and manual search for published studies investigating silicone
      microimplants therapy for stress urinary incontinence in adult women. The
      methodological quality of the included studies was assessed using criteria based
      on generally accepted principles of interventional research. RESULTS: Only two
      RCTs, only published as an abstract, were found. Eleven pre-experimental or
      observational studies were identified. Overall, the methodological quality was
      low. The main methodological shortcomings of the studies were: no random
      allocation procedure, lack of prestratification on prognostic determinants, no
      blinding, small sample sizes, and lack of proper analysis and presentation of
      results. There was variability in the indication for implantation, implantation
      procedure, rate and volume of silicone microimplants. The use of different
      outcome measures in most of the trials made comparison between studies difficult.
      CONCLUSIONS: Because of the low methodological quality of included studies,
      results should be interpreted with caution and no firm conclusions about the
      efficacy of silicone microimplants were possible. Randomized clinical trials,
      using valid and reliable subjective and objective measurements, are necessary to
      establish the efficacy of silicone microimplants therapy in treating stress
      urinary incontinence in adult women.

PMID- 14572758
TI  - Sweating attacks: key symptom in menopausal transition only for women?
AB  - OBJECTIVES: Aging men are not as much aware of the fact as women that they, too,
      undergo some kind of menopausal transition and they notice the symptoms rarely.
      The key symptom of "hot flushes/sweating" is undisputed among women. The
      objective of this paper is to compare the frequency of episodes of sweating
      across gender and age groups. METHODS: A sample of 500 German males and a control
      sample of 153 women were asked to report about the frequency of types/causes of
      "sweating" in the course of aging. RESULTS: Overall, the various types of
      sweating do not show any differences in frequency between males and females. A
      precipitous rise in frequency can be found in the 6th decade of life for both
      sexes. This applies in particular to sudden, unexpected episodes of sweating or
      constriction/anxiety with or without sweaty skin that occur at night (less
      frequently during the day), i.e. occurring without any obvious physical or mental
      stress. This seems to be an important symptom for the changes occurring at an age
      of over 50 years for both sexes. CONCLUSION: Sensations of sweating occurring
      suddenly and unexpectedly, especially at night, but also during the day, seem to
      be similarly common and men and women.

PMID- 14572759
TI  - Lower urinary tract symptoms and erectile dysfunction: co-morbidity or typical
      "Aging Male" symptoms? Results of the "Cologne Male Survey".
AB  - OBJECTIVES: Due to demographic developments in industrial nations, age-correlated
      diseases are becoming more important. From many epidemiological studies we know
      that the prevalence of benign prostatic hyperplasia (BPH) and the loss of
      erectile function (= erectile dysfunction or ED) increase with advancing age. Are
      these two illnesses related or/and independent? METHODS: We mailed our newly
      developed and validated questionnaire on male erectile dysfunction (KEED), as
      well as a set of questions pertaining to voiding problems (IPSS), to a
      representative population sample of 8000 men from 30 to 80 years of age residing
      in the city of Cologne. RESULTS: The responses included 4489 evaluable replies
      (56.1%). The response rates in the different age groups ranged from 41 to 61%.
      The mean age of the men who answered was 51.8 years. The overall prevalence of ED
      was 19.2% (n=862), with a steep age-related increase from 2 to 53%. Furthermore,
      31.2% (n=1957) of all men complained of lower urinary tract symptoms (LUTS), the
      prevalence and the intensity of which increased with age. Interestingly, a high
      co-morbidity was found between ED and voiding problems. Prevalence of LUTS in men
      suffering from ED was about 72.2% (n=621) vs. 37.7% (1367) in men with normal
      erections. The odds ratio was evaluated with 2.11. The trivariate analysis showed
      that the occurrence of LUTS can be considered as an age-independent risk factor
      for the development of ED (p<0.001). CONCLUSIONS: Even though the pathogenetic
      relationship between LUTS and ED is not yet completely understood, one has to
      postulate a direct association between these two typical symptom complexes in the
      aging male.

PMID- 14572760
TI  - The alteration of urine composition due to stone material present in the urinary
      tract.
AB  - OBJECTIVES: Based on a recently introduced mathematical model approach we show
      that uroliths located in the urinary tract (UT) can substantially deplete the
      urinary concentrations of lithogenic constituents by continuous growth. METHODS:
      To illustrate the influence of the urinary depletion effect on urinalysis, a
      "typical" calcium oxalate (CaOx) stone former, presently not stone-free, was
      investigated. Serum and urine samples were analyzed. Several metabolic tests were
      performed. Crystallization risk according to the BONN-Risk-Index (BRI) and the
      relative supersaturation in respect to CaOx (RS(CaOx)) were determined. X-ray
      films taken before and after a period of six months were evaluated in order to
      estimate stone size and average stone growth rate taken place within that period.
      RESULTS: Regarding CaOx urolithiasis the urine samples show a pathologically
      altered pH, a low 24h-citric acid excretion, and a low 24h-urine volume. Neither
      calcium nor oxalate excretion data reflect values indicating these substances as
      risk factors. However, BRI and RS(CaOx) reflect a high crystallization risk. The
      patient's intestinal oxalate absorption is high. Applying the depletion model,
      the patient's 24h-urine composition shifts from normooxaluric to hyperoxaluric.
      CONCLUSION: In the patient, a hitherto undetected hyperoxaluria is diagnosed when
      in-vivo stone growth is taken into account. This is a clear indication that the
      metabolic status can only be evaluated correctly in "stone-free" patients. Any
      stone material present in the UT must be considered in urinalysis interpretation
      as the stone-related urinary depletion effect is of high clinical relevance. A
      helpful nomogram is presented, allowing the estimation of the extent of urinary
      depletion caused by CaOx uroliths.

PMID- 14572761
TI  - Reconstructive urethroplasty using porcine acellular matrix.
AB  - Long tract urethral reconstruction nowadays still has no other resolution than
      two-stage techniques or graft and flap procedures that are neither simple nor
      trouble-free both for the patient and the surgeon. Tissue engineering simplifies
      this surgery using "porcine acellular matrix", obtained from small intestine
      submucosa. It is thin but strong, just ready for grafting, without rejection,
      because it is not immunogenic, being deprivated of cells. It serves as biological
      bridging of the reconstruction, promoting the generation of surrounding tissue in
      which it is completely transformed. We report the first use of porcine intestine
      submucosa in urethroplastic surgery. The up to date follow up is sixteen months
      with satisfactory urodynamic and subjective outcome.

PMID- 14572762
TI  - Comparison of partial urethral replacement with acellular matrix versus
      spontaneous urethral regeneration in a canine model.
AB  - OBJECTIVE: To determine whether acellular matrix could be used for partial
      urethral replacement and to compare regeneration over acellular matrix versus
      normal spontaneous urethral regeneration. MATERIALS AND METHODS: The study
      included 21 male mongrel dogs in which a 3-cm segment including half of the
      urethral circumference was excised. In 13 dogs (study group), the defect was
      covered by acellular matrix of the same length and width obtained from female
      mongrel dogs and prepared to have complete cell lysis with keeping of the fiber
      framework. In 8 dogs (control group), the urethral defect was not covered by any
      urethral tissue. In both groups, an 8F feeding tube was kept inside the urethra
      for a mean duration of 2 weeks. In the study group, dogs were sacrificed at 1
      week, 2 weeks, 3 weeks and then one dog every month for 10 months. In the control
      group, one dog was sacrificed every month for 8 months. RESULTS: All dogs
      survived the procedure. In the study group, 10 dogs underwent urethrogram; 8 were
      normal, 1 had diverticulum and 1 had relative narrowing. In the control group, 6
      dogs underwent urethrogram; 5 were normal and 1 showed relative narrowing.
      Histopathological examination of the study group showed gradual regeneration over
      the acellular matrix with normal appearance at 20 weeks. In the control group,
      normal healing was observed at 2 months and thereafter. CONCLUSION: Regeneration
      of all components of the urethra can occur gradually over acellular matrix and is
      complete at 20 weeks. Regeneration of a urethral defect 3-cm long including half
      of the urethral lumen is possible with or without acellular matrix.

PMID- 14572763
TI  - Urethral reconstruction: new materials but old problems?

PMID- 14572764
TI  - Urethroplasty in female-to-male transsexuals.
AB  - OBJECTIVE: Female-to-male transformation includes total phallic reconstruction.
      Construction of a neourethra is necessary to achieve the goal of voiding while
      standing; however urethral fistula and stricture formation occur in a significant
      percentage of patients. METHODS: 25 patients with primary female transsexualism
      underwent phalloplasty with a free radial forearm flap, vaginectomy and
      urethroplasty in a one-stage procedure. In 16 of these patients the fixed part of
      the neourethra ("bulbar urethra") was constructed from a vaginal flap. In 9
      patients flaps of the labia minora (5 patients) or the "urethral plate" (4
      patients) were used. RESULTS: In 14 (58%) patients fistulas and/or strictures in
      the newly constructed urethra occurred. 11 (69%) of 16 patients in whom the
      "bulbar urethra" was constructed from a vaginal flap experienced fistulas and/or
      stricture formation. Fistulas and/or strictures occurred in 3 of 5 patients with
      labia minora flaps and none of 4 patients with the urethral plate procedure.
      Repair of fistula and strictures was performed by primary closure of fistulas,
      staged urethroplasty with local pedicle flaps or distant tissue grafts using
      buccal mucosa (2-6 procedures). CONCLUSION: One-stage total phalloplasty and
      urethroplasty is associated with a significant rate of fistulas and strictures.
      However, these complications can be corrected by the techniques used in modern
      urethral surgery.

PMID- 14572765
TI  - Pharmacokinetics of intravesical gemcitabine: a preclinical study in pigs.
AB  - INTRODUCTION: Gemcitabine is a deoxycytidine analogue, used intravenously in the
      treatment of several tumours, including transitional cell carcinoma of the
      bladder. It has been shown to be effective and well tolerated when given
      systemically. We investigated the use of this agent administered intravesically
      in pigs for histological studies of the bladder and pharmacokinetic research.
      MATERIAL AND METHODS: Two groups of 5 female pigs each received once 175mg and
      350mg gemcitabine intravesically for 2 hours. A third group of 5 pigs received
      350mg gemcitabine weekly for 6 weeks. Animals were observed for clinical signs of
      toxicity. Blood was withdrawn for gemcitabine pharmacokinetics and in group 3
      also for peripheral blood counts. The animals were euthanized 24 hours after (the
      last) instillation. Histological examination of the bladder wall was performed.
      RESULTS: Doses of 175 and 350mg gemcitabine were well tolerated. The animals
      showed no signs of deterioration of their well-being. Peripheral blood counts
      showed no signs of immunosuppression in the third group. In none of the pigs
      systemic absorption was seen, up to 4 hours after the beginning of instillation.
      Histology showed in all cases normal bladder wall histology, except for some
      cases with mild signs of infection (mainly group 3). CONCLUSION: The use of
      gemcitabine as an intravesical agent in pigs is well tolerated, has no bladder
      toxicity and is not absorbed systemically.

PMID- 14572766
TI  - Intragraft gene and protein expression in rat liver allografts treated with
      costimulatory blockade alone or in combination with CyA.
AB  - BACKGROUND: Costimulatory blockade has been shown to prevent acute rejection (AR)
      and promote long-term graft survival in a number of animal models including
      nonhuman primates. The effect of concomitant administration of conventional
      immunosuppressives on long-term liver allograft survival and intragraft
      expression of immune mediators has not previously been examined. MATERIALS AND
      METHODS: A high-responding Dark Agouti to Lewis orthotopic liver transplant (LEW
      OLT) model was used to compare anti-CD154 alone, or in combination with
      cyclosporin (CyA) on allograft survival. Donor-specific reactivity was assessed
      by mixed lymphocyte reaction (MLR) and allogeneic skin grafts. Surviving rats
      were euthanized on day 150 and intragraft gene (CD80, 86, 152, 154, IFN-gamma, IL
      2, IL-6, IL-10, IL-13, TNF-alpha, TGF-beta, IL-7, Fas-ligand, Granzyme B, bax,
      and bcl(2)) and protein (CD4, CD8, ED1, CD154, CD80, CD86) expression was
      measured. RESULTS: Untreated control recipients had a median survival time of 5
      days. Recipients treated with anti-CD154 survived to beyond 150 days with no
      evidence of AR. Concomitant administration of CyA did not alter the long-term
      survival. There was no difference in the serum aspartate aminotransferase between
      treatment groups or a change over time. All treated recipients showed a reduction
      in donor-specific MLR at day 40 and 60 but had persistence of donor reactivity to
      skin grafts at day 100. Histologically, liver architecture was well preserved
      despite the presence of a nondestructive mononuclear cell infiltrate. Analysis of
      intragraft gene expression revealed an inverse relationship between the duration
      of anti-CD154 therapy and the gene expression of costimulatory molecules and Th1
      cytokine transcripts. The pro-apoptotic gene, bax, was increased in recipients
      treated with anti-CD154, but not CyA, compared with normal liver. CONCLUSIONS:
      These data demonstrate that anti-CD154 therapy either alone or in combination
      with CyA allows for the long-term survival of liver allografts in the rat despite
      there being a difference in the intragraft gene and protein profile.

PMID- 14572767
TI  - High expression of the CD14 gene and interleukin-1beta gene in the liver and
      lungs of cirrhotic rats after partial hepatectomy.
AB  - BACKGROUND: A hepatic resection is invasive for cirrhotic patients because
      postoperative complications, such as hepatic disturbance sometimes resulting in
      hepatic failure and pulmonary disturbances, are frequent and serious. We
      investigated here the alteration of the CD14 and inflammatory cytokine genes
      expressed in the liver and lungs after partial hepatectomy (PH) of a cirrhotic
      rat model to help elucidate the pathophysiological change occurring during the
      postoperative course of hepatectomized cirrhotic patients. MATERIALS AND METHODS:
      Wistar rats were orally administrated carbon tetrachloride once a week for 14
      weeks to induce liver cirrhosis. In comparison with cirrhotic and normal rats, we
      analyzed the expression of the CD14, tumor necrosis factor-alpha, and interleukin
      (IL)-1beta genes in remnant liver and whole lung tissue during 48 h after 30%
      partial hepatectomy with Northern blottings and measured asparatate
      aminotransferase (AST) in serum for evaluation of postoperative hepatic injury.
      Gadolinium chloride (GdCl3; 7 mg/kg body weight) was intravenously injected 24 h
      before partial hepatectomy to suppress Kupffer cells (KC) activation. RESULTS:
      The expression of the CD14 and IL-1beta genes moderately increased at 6 h and
      peaked at 12 h in parallel with the time course of AST values after PH only in
      cirrhotic rats. GdCl(3) significantly inhibited the elevation of AST similar to
      the inhibition of the expression of the CD14 and IL-1beta genes after PH. In
      addition, the expression of these genes showed marked enhancement in the lungs of
      the cirrhotic hepatectomy model. CONCLUSIONS: KC activation was responsible for
      hepatic injury after PH, and the CD14 system appeared to be an early trigger for
      KC activation followed by induction of inflammatory cytokine IL-1beta synthesis
      leading to hepatic injury. Furthermore, the CD14 system was suggested to
      participate in respiratory disturbances after hepatectomy in cirrhosis.

PMID- 14572768
TI  - Role of bile in intestinal barrier function and its inhibitory effect on
      bacterial translocation in obstructive jaundice in rats.
AB  - BACKGROUND: Our previous study using genetically labeled Escherichia coli strain
      JNW14 revealed that obstructive jaundice promotes bacterial translocation in rats
      and that the absence of bile in the intestinal tract is considered to be a factor
      inducing bacterial translocation. The aim of this study was to investigate the
      role of bile and bile acids in intestinal barrier function against bacterial
      translocation. MATERIALS AND METHODS: Eight-week-old male specific-pathogen-free
      Wistar rats were subjected to ligation of their common bile ducts (CBDL). The
      CBDL rats were treated with bacitracin, neomycin sulfate, and streptomycin
      sulfate, and the intestinal tract was colonized with E. coli strain JNW14, which
      was genetically labeled with resistant markers against the above three
      antibiotics, to monitor the bacterial translocation. The rats were then
      administered saline, cholic acid (20 mg/100 g BW), taurocholic acid (TCA: 5-50
      mg/100 BW), or bile (1.5-6 mL/day) via a duodenal catheter. The degree of
      bacterial translocation of E. coli strain JNW14 to the mesenteric lymph nodes was
      compared. Histopathological examination of the terminal ileum and intestinal
      permeability test using phenolsulfonphthalein was also performed. RESULTS: Both
      cholic acid and TCA showed no inhibitory effect on bacterial translocation at any
      of the doses tested in CBDL rats, although TCA significantly decreased the
      numbers of E. coli strain JNW14 in the cecum. However, bile administration
      reduced the numbers of E. coli strain JNW14 in the cecum and mesenteric lymph
      nodes in CBDL rats although the inhibitory effect was weak. The integrity and
      permeability of the intestinal mucosa were kept at normal levels by bile
      administration in CBDL rats whereas the morphological changes, such as villous
      atrophy, villous edema, and lacteal canal dilatation, were observed in other CBDL
      rats. CONCLUSION: Bile plays an important role in maintaining the intestinal
      barrier function to prevent the invasion of enteric bacteria to the underlying
      tissues, suggesting that the intestinal administration of bile to patients with
      obstructive jaundice is a useful way to reduce infectious complications by
      inhibiting bacterial translocation from the intestine to other organs.

PMID- 14572769
TI  - Overexpression of inducible nitric oxide synthase in gastric mucosa of rats with
      portal hypertension: correlation with gastric mucosal damage.
AB  - BACKGROUND: An increased biosynthesis of nitric oxide (NO) has been implicated in
      the hyperdynamic circulation and development of collaterals of portal
      hypertension (PHT) because of its potent vasodilatory effects. NO is synthesized
      from L-arginine by three different isozymes of nitric oxide synthase (nNOS, iNOS
      and eNOS). Thus, the expression of inducible NOS (iNOS) might account for NO
      overproduction in PHT. However, in previous investigations, the role of iNOS in
      the pathogenesis of PHT gastropathy remained controversial. Our current study was
      in both molecular and protein levels to determine whether the expression of iNOS
      is responsible for PHT gastropathy. MATERIALS AND METHODS: PHT was induced
      experimentally by partial ligation of the portal vein. Fourteen days after
      partial ligation of the portal vein, the rats were randomly assigned to receive
      either vehicle or L-NAME (NOS inhibitor) at doses of 5 mg/kg/day, 10 mg/kg/day,
      or 25 mg/kg/day by gastric lavage twice a day for 1 week. Sham operated rats
      served as controls. Northern hybridization and in situ hybridization are used to
      compare the expression of gastric mucosa iNOS mRNA in the PHT rats and the
      controls. NO was measured by the Griess method after reduction of nitrate to
      nitrite with nitrate reductase. Immunohistochemical staining was carried out to
      detect the iNOS protein. In addition, the severity of gross gastric mucosal
      lesions was evaluated macroscopically by a gross ulcer index. RESULTS: The iNOS
      expression at both mRNA and protein was prominently increased in PHT rats,
      accompanied with the enhanced NO production. The gastric mucosa iNOS mRNA and
      serum NO levels were significantly decreased after L-NAME administration (P <
      0.05). However, the markedly reduced gastric mucosal damage in PHT rats was
      observed only at high does of L-NAME (25 mg/kg/day) administration. CONCLUSION:
      PHT triggers overexpression of iNOS mRNA and proteins in rat gastric mucosa, but
      that this alone does not account for PHT gastropathy.

PMID- 14572770
TI  - Effects of the endothelin-1 receptor antagonist tezosentan on renal blood flow
      and diuresis during prolonged increased intra-abdominal pressure.
AB  - BACKGROUND: It has earlier been shown that increased intra-abdominal pressure
      (IAP) reduces renal blood circulation and urine output both clinically and
      experimentally. The aim of this study was to investigate the effect of endothelin
      1 inhibition by the endothelin-1 receptor antagonist tezosentan on renal blood
      circulation and diuresis in pigs subjected to prolonged increased intra-abdominal
      pressure. MATERIAL AND METHODS: The IAP in domestic pigs was maintained at 30
      mmHg for 3 h. One group of 10 animals was pre-treated with the endothelin-1
      receptor antagonist tezosentan, and then received continuous infusion of
      tezosentan throughout the experiment. Another group of 10 animals served as
      control. We measured renal cortex blood flow, plasma renin activity, blood
      concentrations of endothelin-1 and aldosterone, and diuresis. RESULTS: The
      administration of tezosentan to pigs with an IAP of 30 mmHg was followed by
      reduced arterial pressure, reduced renal cortex blood flow, and reduced diuresis.
      The plasma renin activity increased markedly, but neither renal vascular
      resistance nor blood concentration of aldosterone did change significantly.
      CONCLUSION: Tezosentan reduced the arterial blood pressure, which resulted in
      decreased renal cortex blood flow, and aggravation of the oliguria usually
      observed under increased IAP. The plasma renin activity increased, but this was
      not followed by changes in renal vascular resistance, or blood concentration of
      aldosterone. The results indicate that drugs, which reduce the arterial pressure,
      may be harmful to the kidneys under increased IAP.

PMID- 14572771
TI  - Somatostatin receptor gene transfer inhibits established pancreatic cancer
      xenografts.
AB  - BACKGROUND: Most human pancreatic adenocarcinoma cells do not express
      somatostatin receptors, and somatostatin does not inhibit the growth of these
      cancers. We have demonstrated previously that somatostatin inhibits the growth of
      pancreatic cancers expressing somatostatin receptor subtype-2 (SSTR2), but not
      receptor-negative cancers. SSTR2 expression may be an important tumor-suppressor
      pathway that is lost in human pancreatic cancer. We hypothesized that SSTR2 gene
      transfer would restore the growth-inhibitory response of human pancreatic cancer
      to somatostatin. MATERIALS AND METHODS: Palpable human pancreatic adenocarcinoma
      tumors were established on the backs of nude mice by subcutaneous injection of
      cultured cells (Panc-1). The animals were divided into 5 groups (n = 10/group).
      Group I served as an untreated control. Group II received an intramuscular
      injection of the long-acting somatostatin analogue Sandostatin LAR. Group III
      received Lac-Z expressing adenovirus via intraperitoneal injection. Group IV
      received SSTR2 expressing adenovirus via intraperitoneal injection. Group V
      received SSTR2 expressing adenovirus via intraperitoneal injection and an
      intramuscular injection of Sandostatin LAR. The rate of tumor growth was assessed
      with calipers. After 28 days, the animals were anesthetized and exsanguanated,
      and the tumors were excised and weighed. Plasma somatostatin and octreotide
      levels were measured by radioimmunoassay. Expression of cell-surface somatostatin
      receptor protein and known tumor-suppressor proteins was determined by reverse
      transcriptase-polymerase chain reaction, Western blot, and immunohistochemistry.
      RESULTS: Systemic delivery of SSTR2-expressing adenovirus by intraperitoneal
      injection resulted in expression of SSTR2 protein in the subcutaneous human
      pancreatic cancers. Final tumor weight was significantly decreased in the groups
      expressing SSTR2 receptors compared to the other 3 groups. Treatment with
      Sandostatin LAR increased plasma octreotide levels as determined by
      radioimmunoassay, but had no significant effect on tumor growth. Western blot
      analysis revealed an up-regulation of the cyclin-dependent kinase inhibitors p27
      and p16 in the SSTR2 transfected tumors. CONCLUSIONS: Expression of SSTR2 by
      human pancreatic cancer causes significant slowing of tumor growth by a mechanism
      independent of exogenous somatostatin. The mechanism may involve up-regulation of
      known tumor-suppressor proteins. Restoration of SSTR2 gene expression deserves
      further study as a potential gene-therapy strategy in human pancreatic cancer.

PMID- 14572773
TI  - Activation of pulmonary mitogen-activated protein kinases during cardiopulmonary
      bypass.
AB  - PURPOSE: Cardiopulmonary bypass (CPB) produces an inflammatory response
      associated with pulmonary dysfunction. Mitogen-activated protein kinases (MAPK)
      have been shown to mediate pulmonary injury. We hypothesized that MAPK are
      activated during CPB and potentially contribute to lung injury. METHODS: Pigs
      were placed on CPB (n = 6) for 90 min, which included 80 min of cardioplegic
      arrest, followed by 180 min of post-CPB reperfusion. Control animals (n = 6)
      underwent sternotomy and heparinization only. Lung samples were collected at
      baseline, during CPB, and during post-CPB reperfusion. Activated forms of
      extracellular signal-regulated kinases 1/2 (ERK1/2) and p38 were measured by
      Western blot. Immunohistochemistry was used for tissue localization of activated
      MAPK. Pulmonary inflammation was determined by histology. Pulmonary edema was
      estimated by tissue water percentage. RESULTS: Activated ERK1/2 and p38 were
      increased after 90 min of CPB compared with controls (3.94 +/- 0.61- and 2.49 +/-
      0.15-fold increase, respectively; both P < 0.01). At 180 min of post-CPB
      reperfusion, ERK1/2 activity was increased by nearly 5-fold compared with
      controls (P < 0.01), whereas p38 activity returned to baseline levels. By
      immunohistochemistry, activated ERK1/2 and p38 in the CPB group were localized to
      alveolar epithelial cells, vascular endothelial cells, and bronchial smooth
      muscle. Histologic signs of lung injury included leukocyte infiltration in the
      CPB group. Tissue water percentage was increased with CPB (89.9 +/- 1.5% versus
      82.5 +/- 1.0%, CPB versus control, P < 0.05). CONCLUSIONS: The results of our
      study demonstrate that CPB increases pulmonary p38 activity and causes sustained
      activation of ERK1/2. MAPK activation thus may in part mediate the pulmonary
      inflammatory response and provide a potential site of intervention to prevent
      pulmonary dysfunction due to CPB.

PMID- 14572772
TI  - Hypothermia protects against gut ischemia/reperfusion-induced impaired intestinal
      transit by inducing heme oxygenase-1.
AB  - PURPOSE: Gut ischemia/reperfusion (I/R) elicits an inflammatory response that
      impairs intestinal transit. We have previously shown that regional intraischemic
      hypothermia (IH) protects against moderate gut I/R-induced mucosal injury, is
      associated with decreased NF-kappaB activity and inducible nitric oxide synthase
      induction and preserves heme oxygenase-1 (HO-1) expression. HO-1 provides
      cytoprotection in various models of oxidant stress. We, therefore, tested the
      hypothesis that IH protects against gut I/R-induced impaired intestinal transit
      via HO-1 induction. MATERIALS AND METHODS: At laparotomy (lap), Sprague-Dawley
      rats had duodenal catheters placed followed by sham or gut I/R (superior
      mesenteric artery occlusion for 75 min) with or without regional IH (15 degrees
      C). Each animal was placed on a heating blanket maintaining systemic normothermia
      (37 degrees C). At 12 or 24 h of reperfusion, small intestinal transit was
      determined by quantitating the distribution of a tracer (FITC dextran) in the
      intestine 30 min after instillation (expressed as geometric center of
      distribution). Ileal samples were obtained for histology and HO-1 expression,
      assessed by Western immunoblot at 12 and 24 h of reperfusion. In separate
      experiments, rats were pretreated with an HO-1 inhibitor Sn protoporphyrin IX (25
      mumol/kg, ip), 1 h before superior mesenteric artery occlusion and transit
      measured as above. RESULTS: Rats treated with I/R had increased histological
      injury and impaired intestinal transit at both 12 and 24 h compared with sham.
      Rats treated with I/R+IH exhibited histological injury and transit comparable
      with sham controls. I/R induced HO-1 expression at 12 and 24 h of reperfusion and
      IH augmented this I/R-induced HO-1 expression. Sn protoporphyrin IX abrogated IH
      protection against histological injury and impaired transit. CONCLUSION: We
      conclude that intraischemic regional hypothermia protects against histological
      injury and impaired intestinal transit caused by severe gut I/R injury.
      Hypothermic protection under these conditions is in part due to HO-1 expression.

PMID- 14572774
TI  - Initial angiogenic response in reduced renal mass after transplantation.
AB  - INTRODUCTION: Shortage of organs is a major problem in kidney transplantation and
      requires novel strategies to increase the number of kidney transplants. To reduce
      the shortage of kidneys, we have proposed transplantation of two halves of one
      kidney into two recipients (hemirenal transplantation, HRT) and have shown its
      feasibility in pig and human kidneys. However, reduced renal mass can lead to
      progressive renal failure in rodents and can reduce the longevity of kidney
      transplants in humans. Recent studies suggest that derangement of angiogenesis
      plays a role in the progressive renal failure after reduction in renal mass in
      rodents. However, since the renal physiology of rats is different from that of
      large animals, we studied angiogenesis in reduced renal mass transplants in pigs
      and determined if the reduction in renal mass has the same effect in large
      animals as that in rodents. MATERIALS AND METHODS: Kidney autotransplantation was
      performed in domestic outbred swine. Heminephrectomy of the autotransplanted
      kidney and nephrectomy of the contralateral kidney were performed 1 week after
      transplantation to reduce the renal mass. Four weeks after transplantation, the
      pigs were sacrificed and the hemirenal and control nephrectomy specimens were
      processed for morphometric analysis of glomerular capillary density and
      immunohistochemical analysis of VEGF expression. Soluble extracts from the
      kidneys were tested in an in vitro angiogenesis assay to determine their activity
      to influence angiogenesis. Statistical analysis with ANOVA was performed on the
      glomerular capillary density in kidney specimens. RESULTS: All these parameters
      of angiogenesis were increased in the reduced renal mass autotransplants as
      compared to normal kidneys or whole kidney autotransplants. Glomerular capillary
      density was increased significantly after reduction in renal mass. VEGF
      expression also was increased progressively by the third week after reduction in
      renal mass. Soluble extract from the reduced renal mass transplants significantly
      increased the in vitro angiogenesis. CONCLUSION: This is the first study to
      demonstrate that angiogenesis is increased in the initial stages of reduction in
      renal mass after transplantation in a large animal model. Increased angiogenesis
      was found in this model earlier than reported in small animal models (2 weeks in
      pigs versus 6 weeks in rats). Taken together with other studies, our data suggest
      that derangement in angiogenesis could play an important role in long-term graft
      function after hemirenal transplantation.

PMID- 14572775
TI  - Do the best students go into general surgery?
AB  - BACKGROUND: Recent match trends by medical graduates have revealed a declining
      interest in general surgery. Our study evaluates the academic strength of recent
      graduates to determine the quality of those matching to general surgery
      residencies. METHODS: All third-year students rotating through the 8-week
      surgical clerkship from July 1998-June 2000 (n = 291) were followed at the
      University of Wisconsin Medical School. Each student completed 4 weeks of general
      surgery and 4 weeks of surgical subspecialties. Match data provided residency
      choices and students were divided into general surgery (GS), surgical
      subspecialty (SS), and nonsurgical (NS) residencies. Student performance was
      based upon National Board of Medical Experiences (NBME) surgery exam, class rank
      and Alpha Omega Alpha (AOA) status. RESULTS: Students at our institution scored
      at the national mean on the NBME exam. GS team, session, and timing of GS
      rotation had no relationship to exam score. Total number of operative cases
      observed was inversely related to exam performance (P = 0.02). Of students
      entering a GS career, most scored below the mean on the NBME exam, 46% graduated
      in the bottom two thirds of the class, and only 6% of AOA members entered a GS
      residency. CONCLUSION: Although many of the strongest medical students select
      surgical residencies, they choose to enter SS careers and not GS careers.

PMID- 14572776
TI  - Inhibition of CD1d activation suppresses septic mortality: a role for NK-T cells
      in septic immune dysfunction.
AB  - BACKGROUND: Studies indicate that following septic insult there is development of
      generalized immune dysfunction in T cells, B cells and phagocytes, which is
      thought to contribute to morbidity and mortality. Specifically, there is a shift
      in the lymphocytes of septic animals toward an increased release of Th2
      cytokines. NK-T cells have been shown to contribute to propagation of the Th2
      response. The influence of NK-T cells on the immune response to septic challenge
      is poorly understood. In this study, we examine whether NK-T cells contribute to
      the immune dysfunction seen following the onset of polymicrobial sepsis, as
      produced by cecal ligation and puncture (CLP). MATERIALS AND METHODS: Male
      129S1/SvImJ mice were pretreated with either rat IgG (isotypic control) or
      monoclonal antibody to CD1d (clone 1B1) (0.5 mg), which blocks signaling/antigen
      presentation via the CD1d cell surface receptor, thereby, ablating the activation
      and differentiation of the NK-T cells. Septic survival with and without anti-CD1d
      (CLP/CD1d) pretreatment was assessed. Mice sacrificed 24 h after CLP were
      assessed for change in splenic %NK-T cell (via flourescense activated cell
      sector) and for splenic, hepatic, and lymphoid/macrophage production of pro
      inflammatory or anti-inflammatory cytokines (via enzyme-linked immunosorbent
      assay). RESULTS: Administration of anti-CD1d reduced septic mortality 35% at 6-10
      d (n = 23 mice/group) (P <.05). There was a consistent increase in the %CD3(+)
      NK1.1(+) cell population (NK-T cells) in septic mice (1.706%), which was markedly
      suppressed by pretreatment with anti-CD1d (0.592%). IL-6 and IL-10 levels were
      suppressed by anti-CD1d in the spleen and blood. CONCLUSIONS: Together these
      findings imply not only that NK-T cells may play a role in mediating the immune
      suppression seen in bacterial sepsis, but that inhibition of their activation
      promotes survival to septic challenge.

PMID- 14572777
TI  - Red wine prevents homocysteine-induced endothelial dysfunction in porcine
      coronary arteries.
AB  - BACKGROUND: Hyperhomocysteinemia is an independent risk factor of coronary artery
      disease. Clinical studies have indicated that moderate red wine consumption is
      associated with a reduction of incidence of coronary artery disease. In this
      study, we determined the effect of red wine on homocysteine- induced endothelial
      dysfunction in porcine coronary arteries. MATERIALS AND METHODS: Porcine coronary
      arteries were dissected from 6 pig hearts and cut into 5-mm ring segments, which
      were assigned into 4 groups (9 rings/group): blank control, homocysteine treated
      (50 muM), red wine treated (0.08% alcohol), and homocysteine plus red wine
      treated. The rings were cultured in cell culture medium with or without treatment
      for 24 h. Myograph analysis was performed with U46619 (10(-7) M) for contraction
      and cumulative bradykinin (10(-9) to 10(-5) M) for endothelium-dependent
      relaxation. The endothelial nitric oxide synthase (eNOS) levels were analyzed by
      RT-PCR, Western blot, and immunohistochemistry. RESULTS: In response to 10(-5) M
      bradykinin, porcine coronary artery rings treated with homocysteine (50 muM)
      showed a significant reduction of endothelium-dependent vasorelaxation by 43% as
      compared to controls (P < 0.05). However, rings treated with red wine (0.08%
      alcohol) plus homocysteine showed no significant difference as compared to
      controls. Endothelium-dependent vasorelaxation was not different between control
      and red wine treated groups. Furthermore, eNOS mRNA density levels were
      significantly reduced by 36% in homocysteine treated group as compared to
      controls (P < 0.05). eNOS protein levels were also substantially reduced in the
      homocysteine-treated group. However, red wine treatment reversed the effect of
      homocysteine-induced eNOS downregulation. CONCLUSIONS: Homocysteine significantly
      impaired endothelial functions including endothelium-dependent vasorelaxation and
      eNOS mRNA and protein levels in porcine coronary arteries; and red wine
      effectively prevented homocysteine-induced endothelial dysfunction. This study
      suggests that protecting coronary endothelial cells from homocysteine damage may
      be an important mechanism of red wine for preventing coronary artery disease.

PMID- 14572778
TI  - Pentoxifylline reduces acute lung injury in chronic endotoxemia.
AB  - BACKGROUND: Pentoxifylline (PTX) attenuates end-organ injury in models of sepsis
      and hemorrhage. PTX is thought to act by inhibiting phosphodiesterase, thus
      increasing cAMP and decreasing tumor necrosis factor-alpha (TNF-alpha) synthesis.
      The effects of PTX on neutrophil and endothelial cell adhesion molecules and,
      ultimately, organ injury in a chronic endotoxemia model have not been studied. We
      hypothesized that continuous infusion of PTX reduces acute lung injury (ALI)
      caused by chronic lipopolysaccharide (LPS) exposure. MATERIALS AND METHODS: Male
      Sprague-Dawley rats were given continuous infusion of LPS, PTX + LPS combined, or
      saline (sham) by implantable pumps. Neutrophil CD11b expression, lung
      histopathology, lung intercellular adhesion molecule-1 (ICAM-1) expression
      assessed by immune staining, serum TNF-alpha, serum interleukin-6 (IL-6), and
      bronchoalveolar lavage (BAL) IL-8 were evaluated at different time points. Lung
      injury was graded in a blinded fashion from 0 (normal) to 4 (severe) for
      interstitial inflammation, neutrophil infiltration, congestion, and edema. Total
      lung injury score (TLIS) was calculated by adding listed categories. White cell
      count in the peripheral blood and in the BAL was also performed. RESULTS: Animals
      treated with PTX + LPS showed a significant reduction in lung injury score, a
      marked decrease in ICAM-1 expression, and a significant decrease in IL-8 levels
      in the BAL and serum IL-6 levels when compared with LPS-treated animals.
      CONCLUSIONS: Continuous infusion of PTX reduces ALI caused by chronic
      endotoxemia. The effect seems to be a result of decreased expression of
      endothelial and epithelial ICAM-1 and modulation of proinflammatory cytokine
      synthesis.

PMID- 14572779
TI  - Influence of endovascular training on fellowship and general surgical training.
AB  - PURPOSE: As endovascular procedures develop, there is a risk of diminished
      training of residents and fellows in traditional open surgery. We evaluated the
      effect of our endovascular program, initiated in 1999 coincident with the Federal
      Drug Administration's approval of endoluminal vascular aortic grafts, on the
      number of endovascular procedures and open abdominal aortic aneurysm (AAA)
      repairs performed in comparison to national trends. METHODS: The experience of
      vascular fellows and chief residents at completion of training (1996-2002) was
      reviewed and compared with the national mean case numbers before and after
      initiation of our endovascular program. RESULTS: The development of an
      endovascular program increased the total number of aneurysms repaired at the
      Robert Wood Johnson (RWJ) Medical School from 49 +/- 15 to 92 +/- 8 per year (P <
      0.01). The number of vascular operations performed by the RWJ fellow increased
      from 320 +/- 48 to 553 +/- 155 per year (P < 0.05). The number of operations
      performed nationally by vascular fellows also increased during the same period,
      but did not reach statistical significance. There was no change in the number of
      open AAA repairs performed by the RWJ fellow or nationally. There was also no
      change in the average number of vascular operations completed by RWJ chief
      residents or nationally (160 +/- 17 versus 157 +/- 1 and 192 +/- 4 versus 189 +/-
      4, respectively; P > 0.05). However, the average number of open AAA repairs
      performed nationally by general surgical chief residents decreased from 10 +/-
      0.3 to 9 +/- 0.4 (P < 0.05). CONCLUSION: An endovascular program can increase the
      total number of AAA repairs performed without influencing the total number of
      vascular operations performed by general surgical chief residents. There was a
      decrease in open AAA repairs performed nationally by general surgical chief
      residents. The advancement of endovascular therapies may decrease the number of
      open procedures available for trainees in both general and vascular surgery.
      Perhaps those that will specialize in the field of vascular surgery should have
      the benefit of those open procedures.

PMID- 14572780
TI  - Behavior of male-specific minor histocompatibility antigen in skin and limb
      transplantation.
AB  - BACKGROUND: Although the role of male-specific minor histocompatibility antigen H
      Y has been increasingly understood in both experimental and clinical organ
      transplantation, little has been investigated on musculoskeletal tissue
      transplantation. This study was performed to describe the behavior of male
      specific minor histocompatibility H-Y antigen in rat skin and whole limb
      transplantation. MATERIALS AND METHODS: Using three different strains of inbred
      rats (Lewis, F344, and Dark Agouti), 75 donor hindlimbs and eighteen skin grafts
      were isogenically transplanted to the sex-mismatched recipients. Recipients were
      observed up to 48 weeks postoperatively. Rejection was monitored by the
      appearance of the skin of the grafted limb and histology. Systemic microchimerism
      was assessed by polymerase chain reaction using Y-chromosome specific primers.
      RESULTS: Skin rejection didn't occur in all limb transplant recipients and
      histology did not show any rejection findings in all components of the limb graft
      through 48 weeks. Successful functional recovery was expected. Stable and high
      level of chimerism (>1%) was detected in the lymphoid tissues in nontreated
      female recipients. Male skin grafts were rejected by Lewis and F344 female
      recipients within 6 weeks postoperatively. All female skin grafts survived in
      male recipients. CONCLUSION: Our results suggest that H-Y antigen can induce
      graft rejection in rat skin graft but causes no rejection reaction in whole limb
      transplantation. Systemic chimerism may play an important role for acceptance of
      sex-mismatched limb graft.

PMID- 14572781
TI  - Vascular endothelial growth factor synthesis by human omental mesothelial cells
      is augmented by fibroblast growth factor-2: possible role of mesothelial cell on
      the development of peritoneal metastasis.
AB  - Although peritoneal metastasis is an important factor determining the prognosis
      of patients with gastrointestinal cancer, the mechanisms have not yet been
      clearly defined. Human peritoneal mesothelial cells (HPMC) are the first line
      against disseminated tumor cells. Recent reports have shown that mesothelial
      cells are capable of secreting various cytokines and growth factors. In this
      study, we isolated human mesothelial cells from surgically resected omental
      tissue and examined the production and interaction of two major angiogenic
      factors, vascular endothelial growth factor (VEGF) and basic fibroblast growth
      factor (FGF-2). Quiescent HPMC produced a considerable amount of VEGF at almost
      the same level as tumor cells. Interestingly, addition of FGF-2 to the culture
      significantly increased the mRNA synthesis and protein secretion of VEGF in a
      dose-dependent manner, as determined by Northern blot and ELISA. The addition of
      0.5 ng/mL FGF-2 was enough to stimulate VEGF production, and the effect reached a
      plateau at 5 ng/mL. Reverse-transcribed polymerase chain reaction (RT-PCR) method
      clarified that the HPMC-derived VEGF consisted mostly of VEGF(121) and VEGF(165),
      which are both predominantly soluble forms. These data suggest that HPMC
      contribute to the development of metastases and the accumulation of malignant
      ascites due to the production of VEGF, especially in cancers that do not express
      enough amount of VEGF.

PMID- 14572782
TI  - Regional hypothermia reduces mucosal NF-kappaB and PMN priming via gut lymph
      during canine mesenteric ischemia/reperfusion.
AB  - BACKGROUND: Mesenteric ischemia/reperfusion (I/R) activates pro-inflammatory
      mediators that exacerbate gut reperfusion injury and prime circulating
      neutrophils that cause remote organ injury. We have shown that regional
      intraischemic hypothermia protects the intestinal mucosa during I/R in rats. In
      this study, we examined the effects of regional hypothermia on I/R-induced
      transvascular protein clearance, NF-kappaB DNA binding activity, and
      polymorphonuclear neutrophil (PMN) priming via gut lymph in a canine mesenteric
      lymphatic fistula model. MATERIALS AND METHODS: Conditioned dogs underwent 60 min
      of mesenteric ischemia, with or without regional intraischemic hypothermia, and 3
      h reperfusion. A mesenteric lymphatic fistula model was used to measure
      transvascular protein clearance and harvest lymph. Biopsies of distal ileum were
      obtained at baseline and 0, 180 min of reperfusion for NF-kappaB DNA binding
      activity using electrophoretic mobility shift assay (EMSA). A kinetic
      spectrophotometric assay was used to determine fMLP stimulated PMN superoxide
      production after priming by gut lymph obtained at baseline and 180 min
      reperfusion. RESULTS: Transvascular protein clearance increased during
      reperfusion compared to baseline, and hypothermia had no significant effect on
      this I/R-induced protein clearance. NF-kappaB activity increased three-fold at
      the end of ischemia and hypothermia prevented this early activation. PMN
      superoxide production increased 19-fold during I/R (0.06 +/- 0.04 versus 1.14 +/-
      0.50 nmol O(2), P < 0.05), but only 2.5-fold during I/R + hypothermia (0.28 +/-
      0.09 versus 0.70 +/- 0.32 nmol O(2), P = 0.2). CONCLUSIONS: Regional
      intraischemic hypothermia prevented early intestinal NF-kappaB activation,
      partially abrogated PMN priming via gut lymph, but had no significant effect on
      increased transvascular protein clearance during mesenteric I/R in dogs.

PMID- 14572783
TI  - CorLink sutureless aortic anastomotic device: results of an animal study.
AB  - BACKGROUND: The CorLink Automated Anastomotic Device (AD) was developed to create
      a sutureless vein-to-aorta anastomosis without the need to clamp the aorta. This
      study examined the effectiveness and safety of this device in an animal model.
      MATERIALS AND METHODS: Forty-seven vein-to-aorta anastomoses using the AD and 27
      control hand-sutured anastomoses were constructed in 28 sheep. The distal part of
      these grafts were connected either to the main pulmonary artery (40 AD, 20
      control), or to the sheep's brachiocephalic trunk (7 AD, 7 control). Procedural
      details focusing on deployment, leakage, and early patency rates were examined.
      Sheep were sacrificed after periods ranging from 1 to 180 days. Specimens were
      examined grossly and histologically. RESULTS: All but three attempts to construct
      an anastomosis were successful (2 AD, 1 control). All anastomoses were patent
      immediately after their construction. There was no difference between control and
      AD anastomoses in respect to flow rates at the end of operation and before
      sacrifice. No metal breaks were detected. Fourteen of the 47 AD anastomoses and 6
      of the control anastomoses (29.8% versus 22.2% P = ns) were occluded at autopsy.
      Histological findings characteristic of the healing process, were evenly
      distributed between AD and control anastomoses in both models. Intimal thickening
      was found in a notable number of anastomoses, but without any significant
      difference between the AD and control sutured (44.7% versus 40.7% P = ns).
      CONCLUSIONS: The AD proved safe and effective for the construction of proximal
      vein-to-aorta anastomoses as compared to control hand-sutured anastomoses.

PMID- 14572784
TI  - The influence of continuous seven-day elevated intra-abdominal pressure in the
      renal perfusion in cirrhotic rats.
AB  - Since hepatorenal syndrome is a functional renal failure due to renal ischemia in
      cirrhotics with refractory ascites, we investigated whether increased intra
      abdominal pressure (IAP) impairs the renal function and perfusion in cirrhotic
      portal hypertensive rats. Eight groups of 32 rats each were studied, including 4
      control and 4 CCl(4) cirrhotic groups. These were subdivided into two groups
      each, with and without an increased IAP, and further subdivided into groups of
      rats with and without NO inhibition. IAP was increased to 20 mm Hg for 7
      consecutive days by means of an intraperitoneally placed balloon filled with
      water. The animals were studied in normal conditions and after inhibition of NO
      synthesis. Changes in mean arterial pressure and renal microcirculation by means
      of femoral artery catheterization and laser-Doppler technique, respectively, were
      recorded. Venous samples for determination of plasma renin-aldosterone activity,
      biochemical parameters of liver and renal function, and plasma nitrite/nitrate
      levels as an index of NO synthesis were drawn. Cirrhotic rats showed decreased
      renal microcirculation (P = 0.05), while elevated IAP produced a further decrease
      (P = 0.01). Renin-aldosterone levels found increased (P = 0.001) in cirrhotics,
      and elevated IAP produced a further increase (P = 0.01] in both groups.
      Inhibition of NO synthesis resulted in a nonsignificant decrease in both renal
      microcirculation and renin-aldosterone levels in all experimental groups. Liver
      and renal function was found to be impaired in cirrhotics, but increased IAP had
      a nonsignificant further functional impairment in both organs. In conclusion,
      chronically elevated IAP in cirrhotic rats is associated with an increase in
      renin-aldosterone levels and significant impairment of renal perfusion.

PMID- 14572785
TI  - Sepsis-induced failure of hepatic energy metabolism.
AB  - HYPOTHESIS: Recent evidence suggests that sepsis may induce an uncoupling of
      oxidative phosphorylation. The purpose of this study was to quantify temporal
      changes in hepatic oxygen consumption and cellular energy state with increasing
      severity of sepsis and thus assess the interrelationship of these parameters as
      either primary defect or compensatory response. MAIN OUTCOME MEASURES:
      Pseudomonas aeruginosa was infused intravenously in eight instrumented
      anesthetized swine inducing a progressive severity of sepsis to shock. Eight
      other animals served as instrumented controls. Hepatic blood flow, oxygen use,
      and concentrations of ATP, ADP, AMP, NAD(+), and NADH were measured at baseline
      and then sequentially during the study. RESULTS: Except for an increase in heart
      rate, there were no temporal changes in measured values for the control animals.
      For swine receiving P. aeruginosa, hepatic oxygen delivery and consumption
      increased with early sepsis whereas there were no alterations in the
      concentrations of adenine nucleotides or NAD(+)/NADH within liver. Septic shock
      was notable for a decrease in oxygen delivery yet oxygen consumption remained
      elevated because of an increase in percent oxygen extraction. The hepatic
      concentrations of ATP and NADH decreased during septic shock. CONCLUSIONS: These
      findings suggest that any sepsis-induced limitation in phosphorylation may be
      initially compensated by an increase in oxygen use. This study also suggests that
      decreases in NADH availability may be a principal factor in the decompensation of
      sepsis to shock.

PMID- 14572786
TI  - Oral glutamine attenuates surgical manipulation-induced alterations in the
      intestinal brush border membrane.
AB  - BACKGROUND: Our earlier work has shown that surgical manipulation of the
      intestine results in oxidative stress and mucosal damage along with alterations
      in the brush border membrane (BBM). Glutamine feeding is known to offer
      protection against damage to mucosa under various conditions and this study
      looked at the effect of oral supplementation of glutamine or glutamic acid in the
      intestinal BBM alterations after surgical manipulation. MATERIALS AND METHODS:
      Control and rats pretreated for 7 days with 2% glutamine or glutamic acid or
      isonitrogenous amino acids, glycine, or alanine were subjected to surgical
      manipulation of the intestine. BBMs were isolated from the intestine and
      functional and structural alterations to these membranes were assessed and
      compared. RESULTS: Surgical manipulation resulted in oxidative stress in the
      enterocyte BBM and these changes included a decrease in alkaline phosphatase
      activity and alpha-tocopherol content along with an increase in lipid
      peroxidation parameters. A decrease in glucose transport by the isolated BBM
      vesicles suggested functional impairment. Surgical manipulation also resulted in
      phospholipid degradation possibly mediated by PLA(2) and membrane protease
      activation. Glutamine or glutamic acid supplementation prevented these changes
      but not by glycine or alanine. CONCLUSION: This study suggests that oral
      glutamine or glutamic acid supplementation prior to surgery can offer protection
      to the intestine and this might prevent postsurgical complications.

PMID- 14572787
TI  - A murine model of thoracic aortic aneurysms.
AB  - BACKGROUND: The mechanisms of thoracic aortic aneurysm (TAA) formation are poorly
      understood, mainly due to the lack of a useful and reproducible model.
      Accordingly, the goal of this study was to test the hypothesis that abluminal
      calcium chloride (CaCl(2)) application could create TAAs in the mouse. MATERIALS
      AND METHODS: Adult 129/SvE mice (n = 8) were anesthetized and their thoracic
      aortas exposed via left thoracotomy. CaCl(2) (0.5M) was applied to the distal
      descending thoracic aorta for 15 min followed by chest closure. At 4 weeks, the
      perfusion-fixed aorta was harvested from the root to the renal arteries. Diameter
      measurements were made using confocal microscopy, and wall thickness was measured
      from hematoxylin and eosin-stained sections. RESULTS: The control (n = 15) distal
      descending thoracic aortic diameter was 0.60 +/- 0.04 mm and increased by 25%
      (0.76 +/- 0.06 mm, P < 0.05) following CaCl(2) treatment. Control aortic wall
      thickness was 48 +/- 9 mum and decreased by 47% in corresponding CaCl(2)-exposed
      segments (25 +/- 8 mum, P < 0.05). The diameter and wall thickness of the
      ascending aorta (used as an internal control) were not significantly different
      between groups. Picrosirius red staining of the TAA showed adventitial collagen
      breakdown and disruption of lamellar organization. CONCLUSIONS: We conclude that
      abluminal application of CaCl(2) to the thoracic aorta reliably produces
      dilation, wall-thinning, and disruption of mural architecture, the hallmark signs
      of aneurysm formation. To our knowledge, these findings describe for the first
      time the generation of a reproducible model of isolated TAA formation in a murine
      system.

PMID- 14572788
TI  - Growth hormone and epidermal growth factor together enhance amino acid transport
      systems B0,+ and A in remnant small intestine after massive enterectomy.
AB  - BACKGROUND: Sodium-dependent brush-border nutrient transport is decreased 2 weeks
      after massive enterectomy. This down-regulation is ameliorated by a 1-week
      infusion of parenteral growth hormone (GH) and epidermal growth factor (EGF)
      started 1 week after resection. We hypothesize that glutamine (GLN) transport
      will be enhanced by earlier and longer growth factor infusion, with differential
      effects on the Na(+)-dependent GLN transport systems A, B(0,+), and B(0)/ASCT2.
      MATERIALS AND METHODS: New Zealand White rabbits underwent 70% small bowel
      resection then immediately received parenteral EGF, GH, both EGF and GH, or
      neither for 2 weeks. Na(+)-dependent 3H-GLN uptake by jejunal and ileal brush
      border membrane vesicles was measured and the contribution of systems A, B(0,+),
      and B(0) was then determined by competitive inhibition. Data were analyzed using
      one-way analysis of variance. RESULTS: In nonresected animals, the relative
      contribution of the systems was similar in jejunum (A 9%, B(0,+) 20%, and B(0)
      71%) and ileum (A 13%, B(0,+) 27%, and B(0) 60%). Na(+)-dependent GLN uptake was
      reduced by one half in resected untreated controls, primarily because of
      decreased B(0) activity. EGF or GH alone did not affect Na(+)-dependent GLN
      transport, but, as a combination, there was increased uptake in the residual
      ileum and jejunum by 144% and 150%, respectively, over resected controls (P <
      0.05). This was twice that achieved by delayed and shorter-duration combination
      treatment. This augmentation was a result of a 6.1-8.2-fold increase in system A
      as well as a 3.8-3.9-fold enhancement of system B(0,+) activity in remnant ileum
      and jejunum (P < 0.01). CONCLUSIONS: Parenteral EGF and GH, given in combination
      for 2 weeks immediately after massive enterectomy, synergistically enhance GLN
      uptake by systems A and B(0,+).

PMID- 14572790
TI  - TGF-beta1 increases microbial clearance but worsens lung injury during
      Escherichia coli pneumonia in rats.
AB  - We investigated the effects of either intravenous (IV) or intrabronchial (IB)
      treatment with transforming growth factor beta1 (TGF-beta1) during bacterial
      pneumonia in rats. Immediately following IB Escherichia coli inoculation (T0),
      animals (n=270) were randomized to receive a single treatment with human
      recombinant TGF-beta1 either via IV or IB, or via both IV and IB routes, or to
      receive placebo (human serum albumin, HSA) only. Blood and lung analysis was done
      at 6 and 168 h after E. coli inoculation. Other animals (n=40) were administered
      IV TGF-beta1 or HSA at T0 and 6, 12 and 24 h after E. coli inoculation to
      investigate the effects of multiple treatments also on survival rates alone. All
      animals received ceftriaxone daily. Route of administration did not influence TGF
      beta1 (p=ns for the effect of TGF-beta1 comparing IV vs IB routes) and we
      averaged over this variable in analysis. The relative risk of death (mean +/-
      sem) was not altered by either single treatments administered at T0 (-0.18 +/-
      0.25, p=0.47) or multiple treatments (0.40 +/- 0.50, p=0.66) of TGF-beta1. Single
      treatment with TGF-beta1 first decreased and then increased vascular leukocytes
      at 6 and 168 h, respectively, but increased alveolar leukocytes at both time
      points (p=0.02 comparing the differing effects of TGF-beta1 on vascular and
      alveolar leukocytes at 6 and 168 h). Although TGF-beta1 decreased blood and lung
      bacteria counts at 6 and 168 h, it also increased serum tumor necrosis factor
      levels and lung injury scores at these time points (p<0.05 for the effects of TGF
      beta1 on each parameter at 6 and 168 h together). Thus, while increases in lung
      leukocyte recruitment with TGF-beta1 were associated with improved microbial
      clearance in this rat model of pneumonia, worsened lung injury may have negated
      these beneficial host defense effects, and overall survival was not significantly
      improved. Despite these harmful effects, additional studies may be warranted to
      better define the influence of exogenous TGF-beta1 on host defense during acute
      bacterial infections.

PMID- 14572791
TI  - Enhanced expression of lymphotactin by CD8+ T cells is selectively induced by
      enhancer agonist peptides of tumor-associated antigens.
AB  - Human tumor-associated antigens (TAAs) are weak immunogens. One strategy for
      increasing the immunogenicity of TAAs is to generate altered peptide ligands. In
      the studies reported here, microarray technology has been used to compare gene
      expression profiles of a human T cell line that was derived from the peripheral
      blood of a cancer patient vaccinated with a carcinoembryonic antigen (CEA)-based
      vaccine. We compared the gene expression profiles of this CEA-specific CD8 T cell
      line when (a) stimulated with the native peptide used to derive this line vs. no
      peptide, and (b) stimulated with its TCR enhancer agonist epitope vs. no peptide.
      The results demonstrate that the effect on the T cell line, when stimulated with
      the agonist peptide, is not an enhanced quantitative expression of the same genes
      or gene sets induced by the native peptide, but is rather a nearly reciprocal
      upregulation of different gene sets. The gene for the chemokine lymphotactin,
      which was overexpressed only in T cells stimulated with the agonist peptide,
      stood out above all others. This finding was extended using other T cell lines,
      and another set of agonist and native peptides from another TAA. ELISPOT and
      ELISA assays for lymphotactin confirmed and extended these findings. These
      studies suggest a potential role for lymphotactin in the T-cell activation
      processes and subsequent anti-tumor events.

PMID- 14572792
TI  - Balance of tumor necrosis factor alpha and interleukin-10 in a buccal infection
      in a streptozotocin-induced diabetic rat model.
AB  - This study evaluates the local levels of proinflammatory cytokine, tumor necrosis
      factor alpha (TNF-alpha), and anti-inflammatory cytokine, interleukin-10 (IL-10),
      in an experimental buccal abscess of a diabetic rat model. We prepared a buccal
      cavity induced by injection of carrageenin in a diabetic rat (blood glucose,
      460.6 +/- 54.7 mg/dl, mean +/- SE) induced by streptozotocin (STZ). The buccal
      abscess was formed by the direct inoculation of Streptococcus pyogenes S-8 (2 x
      10(7) cfu) into the buccal cavity at day 5 after carrageenin injection. Cytokine
      levels in the exudate of the buccal abscess were measured by enzyme-linked
      immunosorbent assay for 48 h after infection. Bacterial counts, weighing of
      exudate, and histological analysis were also performed. The mean TNF-alpha levels
      in the buccal abscess exudate of the diabetic group, which were generally higher
      than those of the control group, tended to increase over time until 48 h after
      infection, while the TNF-alpha levels in the control group peaked at 24 h after
      infection and then decreased. The IL-10 levels in the diabetic group remained
      almost unchanged until 48 h after infection, while the IL-10 levels in the
      control group were significantly higher than in the diabetic group at 12-24 h
      after infection. The mean ratio of TNF-alpha to IL-10 levels was 1.17-1.67 in the
      diabetic group, which was higher than the 0.26-0.69 of the control group. The
      bacterial counts in the buccal abscess and the weight of exudate were
      significantly higher in the diabetic group compared to the control group at 36-48
      h. Histological findings showed that inflammatory cell infiltration was
      remarkable in the diabetic group compared to that of the control group. These
      results suggest that the elevated proinflammatory TNF-alpha levels and decreased
      anti-inflammatory IL-10 levels, which are produced at local infection sites, may
      at least in part be related to the severity of inflammation in this rat model
      with diabetes induced by STZ.

PMID- 14572793
TI  - Murine abortion is associated with enhanced interleukin-6 levels at the feto
      maternal interface.
AB  - CBA/JXDBA/2J murine abortion is known to be associated with increased local and
      peripheral Th1-cytokines levels. The role of the pro-inflammatory interleukin-6
      (IL-6) in murine abortion remains unclear. In humans, IL-6 was reported to be
      elevated at the onset of spontaneous abortion. The aim of our study was to
      evaluate the levels of IL-6 during murine pregnancy in (1) the normal murine
      pregnancy combination CBA/JXBALB/c and in (2) the CBA/JXDBA/2J abortion prone
      mating combination. We measured IL-6 serum levels by ELISA and local (placental
      and decidual) IL-6 levels by flow cytometry and immunohistochemistry. The
      expression of the IL-6 receptor gp80 was further analyzed. We additionally
      evaluated the number of mast cells and macrophages at the feto-maternal interface
      as a putative IL-6 source in reproductive tissues. IL-6 and gp80 were expressed
      in decidual cells as well as in different trophoblast types. Flow cytometry
      analysis showed increased numbers of IL-6+ cells in abortion placentas and
      deciduas compared to control pregnant mice. We observed an elevated number of
      mast cells and macrophages at the feto-maternal interface from abortion mice in
      comparison to control mice. Interestingly, we found very high numbers of mast
      cells, macrophages and IL-6+ cells in resorption tissue compared to control
      tissues. Flow cytometry studies confirmed that macrophages are being an important
      source of IL-6 at the feto-maternal interface. The mRNA IL-6 levels were also
      enhanced in placenta and decidua from mice with high abortion rate compared to
      normal pregnant mice, as analyzed by RT-PCR. Our results suggest that IL-6
      produced not only by immunocompetent cells such as macrophages and mast cells,
      but also by trophoblasts and decidua cells, is directly involved in the pathology
      of abortion.

PMID- 14572794
TI  - Tumor necrosis factor-alpha, lymphotoxin-alpha, and interleukin-10 gene
      polymorphisms and restenosis after coronary artery stenting.
AB  - Inflammation is the primary response to vessel wall injury caused by stent
      placement in coronary arteries. The cytokines tumor necrosis factor (TNF)-alpha,
      lymphotoxin (LT)-alpha, and interleukin (IL)-10 are critically involved in
      inflammatory reactions. The intensity of the inflammatory process and the
      angiographic or clinical outcome after stenting are influenced by genetic
      factors. We investigated the possibility that single nucleotide polymorphisms of
      the genes encoding TNF-alpha (-863C/A, -308G/A), LT-alpha (252G/A), and IL-10 (
      1082G/A, -819C/T, and -592C/A) are associated with the incidence of restenosis,
      death, or myocardial infarction (MI) after coronary stenting. The gene variations
      are known to be correlated with transcriptional activity and/or protein
      production. Our study included 1,850 consecutive patients with symptomatic
      coronary artery disease who underwent stent implantation. Follow-up angiography
      was performed in 1,556 patients (84.1%) at six months after the intervention. We
      found that the polymorphisms are not associated with restenosis, death, or MI. In
      addition, we did not observe a relationship between polymorphism-specific
      haplotypes and adverse angiographic and clinical outcomes. In conclusion,
      functionally relevant polymorphisms of the genes for TNF-alpha, LT-alpha, and IL
      10 do not represent genetic markers indicating the risk of restenosis, death, or
      MI after coronary stenting.

PMID- 14572795
TI  - Alterations in the phenotype of CMV-specific and total CD8+ T-cell populations in
      Wegener's granulomatosis.
AB  - Wegener's granulomatosis (WG) is an autoimmune disease of as yet unknown
      etiology. To date it has remained obscure what causes WG or determines disease
      progression. Case reports suggest that viral infections such as cytomegalovirus
      (CMV) reactivation may contribute to disease flares. In this study we found a
      skewing of the phenotype of CMV-specific CD8+tet(ramer)+ T-cells in WG. A marked
      proportion of these cells displayed a late differentiated "effector memory" T
      cell phenotype with decreased expression of CD28 and CD62L, and heterogeneous
      CD27 expression, features which were also seen in CD8+tet- T-cells in WG, but not
      in controls. Our results might reflect profound generalized changes in the CD8+ T
      cell compartment also affecting virus-specific T-cell responses in WG.

PMID- 14572796
TI  - Peptidoglycan recognition protein expression in mouse Peyer's Patch follicle
      associated epithelium suggests functional specialization.
AB  - Mammalian Peyer's Patches possess specialized epithelium, the follicle associated
      epithelium (FAE), and specialized cells called M cells which mediate transcytosis
      of antigens to underlying lymphoid tissue. To identify FAE specific genes, we
      used TOGA gene expression profiling of microdissected mouse Peyer's Patch tissue.
      We found expression of laminin beta3 across the FAE, and scattered expression of
      peptidoglycan recognition protein (PGRP)-S. Using the M cell specific lectin Ulex
      europaeus agglutinin 1 (UEA-1), PGRP-S expression was nearly exclusively co
      localized with UEA-1+ M cells. By contrast, the related gene PGRP-L was expressed
      among a subset of UEA-1 negative FAE cells. Expression of these proteins in
      transfected cells demonstrated distinct subcellular localization. PGRP-S showed a
      vesicular pattern and extracellular secretion, while PGRP-L showed localization
      to both the cytoplasm and the cell surface. The potential function of these PGRP
      proteins as pattern recognition receptors and their distinctive cellular
      distribution suggests a complex coordination among specialized cells of the FAE
      in triggering mucosal immunity and innate immune responses.

PMID- 14572797
TI  - Red blood cells promote survival and cell cycle progression of human peripheral
      blood T cells independently of CD58/LFA-3 and heme compounds.
AB  - Red blood cells (RBC) are known to modulate T cell proliferation and function
      possibly through downregulation of oxidative stress. By examining parameters of
      activation, division, and cell death in vitro, we show evidence that the increase
      in survival afforded by RBC is due to the maintenance of the proliferative
      capacity of the activated T cells. We also show that the CD3+CD8+ T cell subset
      was preferentially expanded and rescued from apoptosis both in bulk peripheral
      blood lymphocyte cultures and with highly purified CD8+ T cells. The ability of
      RBC to induce survival of dividing T cells was not affected by blocking the
      CD58/CD2 interaction. Moreover, addition of hemoglobin, heme or protoporphyrin IX
      to cultures of activated T cells did not reproduce the effect of intact RBC.
      Considering that RBC circulate throughout the body, they could play a biological
      role in the modulation of T cell differentiation and survival in places of active
      cell division. Neither CD58 nor the heme compounds studied seem to play a direct
      relevant role in the modulation of T cell survival.

PMID- 14572798
TI  - An orally active Th1/Th2 balance modulator, M50367, suppresses Th2
      differentiation of naive Th cell in vitro.
AB  - We previously reported an orally active anti-allergic agent, M50367, modulated
      Th1/Th2 balance to down-regulate Th2 response in a murine model of atopic asthma.
      In this study, we examined the effect of M50354, the active metabolite of M50367,
      on the differentiation of naive Th cells into Th1/Th2 cells. M50354 at 3 microM
      decreased the generation of Th2 cells by 0.2-fold and increased that of Th1 cells
      by 1.6-fold from naive Th cells primed with antigenic peptide and antigen
      presenting cells. Its effect was also seen when naive Th cells were primed with
      anti-T cell receptor and anti-CD28 agonistic antibodies instead of antigen and
      antigen-presenting cells. M50354 decreased early endogenous IL-4 production in
      the nai;ve Th cell priming culture without affecting interferon-gamma production
      and proliferation. In contrast, M50354 had no effect on interferon-gamma and IL-4
      production from mature Th1 and Th2 cells. These results suggest that M50354
      directly acts on naive Th cells to suppress their differentiation into Th2 cells.

PMID- 14572799
TI  - Differential requirements for proliferation of CD4+ and gammadelta+ T cells to
      spirochetal antigens.
AB  - Alphabeta+ and gammadelta+ T cells have different mechanisms of epitope
      recognition and are stimulated by antigens of different chemical nature. An
      immunization model with antigens from the spirochete Brachyspira hyodysenteriae
      was used to examine the requirements for proliferation of circulating porcine
      CD4+ and gammadelta+ T cells in mixed lymphocyte cultures. CD4+ T cells only
      responded to stimulation with B. hyodysenteriae antigens, whereas gammadelta+ T
      cells proliferated when cultures were stimulated with either spirochetal antigens
      or interleukin-2 (IL-2). T cells that had proliferated expressed high levels of
      IL-2-receptor-alpha (IL-2Ralpha). Furthermore, neutralization of IL-2 at the
      beginning of the culture period was more efficient in blocking gammadelta+ than
      CD4+ T cell proliferation. Immunization induced interferon-gamma (IFN-gamma)
      production by CD4+ T cells, whereas only a small fraction of the antigen
      stimulated gammadelta+ T cells produced this cytokine. Our results indicate that,
      under the same environmental conditions, CD4+ T cell functions are more tightly
      regulated when compared to gammadelta+ T cells. We conclude that these
      differences are due, in part, to the enhanced gammadelta+ T cell responsiveness
      to IL-2.

PMID- 14572800
TI  - Anti-allergic drug olopatadine suppresses murine contact hypersensitivity and
      downmodulates antigen-presenting ability of epidermal Langerhans cells.
AB  - Olopatadine hydrochloride is an H1-receptor-blocker but has other anti-allergic
      pharmacological potencies. We investigated whether olopatadine inhibits murine
      contact hypersensitivity, focussing on its modulatory action on epidermal
      Langerhans cells serving as antigen-presenting cells. While BALB/c mice were
      sensitized and challenged epicutaneously with hapten, they were administered
      intraperitoneally with olopatadine. Olopatadine at 1 or 0.2 mg/kg of weight
      significantly suppressed the sensitivity when injected at least once before
      sensitization or challenge. In olopatadine-injected mice, the ability of
      Langerhans cells to present hapten to primed T cells was reduced with decreased
      expression of MHC class II and co-stimulatory molecules. Langerhans cells exposed
      in vitro to 10(-5) or 10(-6) M olopatadine had less antigen-presenting activity
      than control, whereas neither T cell proliferation nor keratinocyte production of
      IL-1alpha and IP-10 was affected at these doses. These findings suggest that
      olopatadine downmodulates contact hypersensitivity at least partly by interfering
      with the antigen-presenting ability of Langerhans cells.

PMID- 14572801
TI  - Gene expression profile of CD4+ T cells reveals an interferon signaling
      suppression associated with progression of experimental Schistosoma japonicum
      infection.
AB  - To understand the natural history of immune responses centering CD4+ T cells at
      genetic level during experimental infection with Schistosoma japonicum (S.
      japonicum), the mRNA profiles of CD4+ T cells from spleens of mice at 0, 3, 6,
      and 13 weeks after the onset of the infection, were compared using mouse
      oliogonucleotide microarrays (Affymetrix GeneChip U74A). Of about 12,000 mouse
      probe sets in a microarray, nearly 10% encoded a variety of immune regulators,
      including many cytokine and chemokine genes, immunoglobulin-related genes, and
      genes related to apoptosis and the stress response. These changed in transcript
      representation as the schistosome infection progressed, and a key finding, which
      was validated by semi-quantitative PCR, was that a significant portion of the
      genes which were down-regulated as infection progressed coded for interferon
      (IFN)-inducible molecules, including GTPases, transcription factors and
      chemokines. The results thus showed that there is a characteristic change in IFN
      inducible gene expression over the course of the schistosome infection, and it is
      suggested that the IFN-gamma-regulated GTPase family may be involved in IFN
      mediated resistance against S. japonicum.

PMID- 14572802
TI  - Crosstalk between cAMP and Ca2+ signaling in non-excitable cells.
AB  - An impressive array of cytosolic calcium ([Ca2+](i)) signals exert control over a
      broad range of physiological processes. The specificity and fidelity of these
      [Ca2+](i) signals is encoded by the frequency, amplitude, and sub-cellular
      localization of the response. It is believed that the distinct characteristics of
      [Ca2+](i) signals underlies the differential activation of effectors and
      ultimately cellular events. This "shaping" of [Ca2+](i) signals can be achieved
      by the influence of additional signaling pathways modulating the molecular
      machinery responsible for generating [Ca2+](i) signals. There is a particularly
      rich source of potential sites of crosstalk between the cAMP and the [Ca2+](i)
      signaling pathways. This review will focus on the predominant molecular loci at
      which these classical signaling systems interact to impact the spatio-temporal
      pattern of [Ca2+](i) signaling in non-excitable cells.

PMID- 14572803
TI  - Formyl-Met-Leu-Phe induces calcium-dependent tyrosine phosphorylation of Rel-1 in
      neutrophils.
AB  - Chemoattractant priming and activation of PMNs results in changes in cytosolic
      Ca2+ concentration, tyrosine kinase activity, and gene expression. We hypothesize
      that the initial signaling for the activation of a 105kDa protein (Rel-1)
      requires Ca2+-dependent tyrosine phosphorylation. A rapid and time-dependent
      tyrosine phosphorylation of Rel-1 occurred following formyl-Met-Leu-Phe (fMLP)
      stimulation of human PMNs at concentrations that primed or activated the NADPH
      oxidase (10(-9) to 10(-6)M), becoming maximal after 30s. Pretreatment with
      pertussis toxin (Ptx) or tyrosine kinase inhibitors abrogated this
      phosphorylation and inhibited fMLP activation of the oxidase. The fMLP
      concentrations employed also caused a rapid increase in cytosolic Ca2+ but
      chelation negated the effects, including the cytosolic Ca2+ flux, oxidase
      activation, and the tyrosine phosphorylation of Rel-1. Conversely, chelation of
      extracellular Ca2+ decreased the fMLP-mediated Ca2+ flux, had no affect on the
      oxidase, and augmented tyrosine phosphorylation of Rel-1. Phosphorylation of Rel
      1 was inhibited when PMNs were preincubated with a p38 MAP kinase (MAPK)
      inhibitor (SB203580). In addition, fMLP elicited rapid activation of p38 MAPK
      which was abrogated by chelation of cytosolic Ca2+. Thus, fMLP concentrations
      that prime or activate the oxidase cause a rapid Ca2+-dependent tyrosine
      phosphorylation of Rel-1 involving p38 MAPK activation.

PMID- 14572804
TI  - Ca2+ transport ATPase isoforms SERCA2a and SERCA2b are targeted to the same sites
      in the murine heart.
AB  - Adult SERCA2(b/b) mice expressing the non-muscle Ca2+ transport ATPase isoform
      SERCA2b in the heart instead of the normally predominant sarcomeric SERCA2a
      isoform, develop mild concentric ventricular hypertrophy with impaired cardiac
      contractility and relaxation [Circ. Res. 89 (2001) 838]. Results from a separate
      study on transgenic mice overexpressing SERCA2b in the normal SERCA2a context
      were interpreted to show that SERCA2b and SERCA2a are differentially targeted
      within the cardiac sarcoplasmic reticulum (SR) [J. Biol. Chem. 275 (2000) 24722].
      Since a different subcellular distribution of SERCA2b could underlie alterations
      in Ca2+ handling observed in SERCA2(b/b), we wanted to compare SERCA2b
      distribution in SERCA2(b/b) with that of SERCA2a in wild-type (WT). Using
      confocal microscopy on immunostained fixed myocytes and BODIPY-thapsigargin
      stained living cells, we found that in SERCA2(b/b) mice SERCA2b is correctly
      targeted to cardiac SR and is present in the same SR regions as SERCA2a and
      SERCA2b in WT. We conclude that there is no differential targeting of SERCA2a and
      SERCA2b since both are found in the longitudinal SR and in the SR proximal to the
      Z-bands. Therefore, alterations in Ca2+ handling and the development of
      hypertrophy in adult SERCA2(b/b) mice do not result from different SERCA2b
      targeting.

PMID- 14572805
TI  - Regulation by clozapine of calcium handling by rat submandibular acinar cells.
AB  - The effect of clozapine on the intracellular concentration of calcium ([Ca2+](i))
      in rat submandibular acinar cells was tested. By itself clozapine had no effect
      on the mobilization of intracellular pools of calcium or on the uptake of
      extracellular calcium. It inhibited the increase of the [Ca2+](i) in response to
      carbachol (half-maximal inhibitory concentrations, IC(50)=100nM) and to
      norepinephrine and epinephrine (IC(50)=10nM) without affecting the response to
      substance P, extracellular ATP or thapsigargin. Clozapine inhibited the uptake of
      extracellular calcium in response to epinephrine but not to substance P, ATP or
      thapsigargin. It also decreased the production of inositol phosphates elicited by
      epinephrine but not by substance P or fluoride. It is concluded that, by itself,
      clozapine has no effect on the [Ca2+](i) in rat salivary acinar cells. It
      selectively inhibits muscarinic and adrenergic receptors in the acinar plasma
      membrane.

PMID- 14572806
TI  - Intracellular alkalinization induces Ca2+ influx via non-voltage-operated Ca2+
      channels in rat aortic smooth muscle cells.
AB  - In smooth muscle, the cytosolic Ca2+ concentration ([Ca2+](i)) is the primary
      determinant of contraction, and the intracellular pH (pH(i)) modulates
      contractility. Using fura-2 and 2',7'-biscarboxyethyl-5(6) carboxyfluorescein
      (BCECF) fluorometry and rat aortic smooth muscle cells in primary culture, we
      investigated the effect of the increase in pH(i) on [Ca2+](i). The application of
      the NH(4)Cl induced concentration-dependent increases in both pH(i) and
      [Ca2+](i). The extent of [Ca2+](i) elevation induced by 20mM NH(4)Cl was
      approximately 50% of that obtained with 100mM K(+)-depolarization. The NH(4)Cl
      induced elevation of [Ca2+](i) was completely abolished by the removal of
      extracellular Ca2+ or the addition of extracellular Ni2+. The 100mM K(+)-induced
      [Ca2+](i) elevation was markedly inhibited by a voltage-operated Ca2+ channel
      blocker, diltiazem, and partly inhibited by a non-voltage-operated Ca2+ channel
      blocker, SKF96365. On the other hand, the NH(4)Cl-induced [Ca2+](i) elevation was
      resistant to diltiazem, but was markedly inhibited by SKF96365. It is thus
      concluded that intracellular alkalinization activates the Ca2+ influx via non
      voltage-operated Ca2+ channels and thereby increases [Ca2+](i) in the vascular
      smooth muscle cells. The alkalinization-induced Ca2+ influx may therefore
      contribute to the enhancement of contraction.

PMID- 14572807
TI  - Sensitivity of CaM kinase II to the frequency of Ca2+ oscillations: a simple
      model.
AB  - The rules that govern the activation and autophosphorylation of the
      multifunctional Ca2+-calmodulin kinase II (CaMKII) by Ca2+ and calmodulin (CaM)
      are thought to underlie its ability to decode Ca2+ oscillations and to control
      multiple cellular functions. We propose a simple biophysical model for the
      activation of CaMKII by Ca2+ and calmodulin. The model describes the transition
      of the subunits of the kinase between their different possible states (inactive,
      bound to Ca2+-CaM, phosphorylated at Thr(286), trapped and autonomous). All
      transitions are described by classical kinetic equations except for the
      autophosphorylation step, which is modeled in an empirical manner. The model
      quantitatively reproduces the experimentally demonstrated frequency sensitivity
      of CaMKII [Science 279 (1998) 227]. We further use the model to investigate the
      role of several characterized features of the kinase--as well as some that are
      not easily attainable by experiments--in its frequency-dependent responses. In
      cellular microdomains, CaMKII is expected to sense very brief Ca2+ spikes; our
      simulations under such conditions reveal that the enzyme response is tuned to
      optimal frequencies. This prediction is then confirmed by experimental data. This
      novel and simple model should help in understanding the rules that govern CaMKII
      regulation, as well as those involved in decoding intracellular Ca2+ signals.

PMID- 14572808
TI  - Optical single-channel recording: imaging Ca2+ flux through individual N-type
      voltage-gated channels expressed in Xenopus oocytes.
AB  - Functional studies of single membrane ion channels were made possible by the
      introduction of the patch-clamp technique, which allows single-channel currents
      to be measured with unprecedented resolution. Nevertheless, patch clamping has
      some limitations: including the need for physical access of the patch pipette,
      possible disruption of local cellular architecture, inability to monitor multiple
      channels, and lack of spatial information. Here, we demonstrate the use of
      confocal fluorescence microscopy as a non-invasive technique to optically monitor
      the gating of individual Ca2+ channels. Near-membrane fluorescence signals track
      the gating of N-type Ca2+ channels with a kinetic resolution of about 10ms,
      provide a simultaneous and independent readout from several channels, and allow
      their locations to be mapped with sub-micrometer spatial resolution. Optical
      single-channel recording should be applicable to diverse voltage- and ligand
      gated Ca2+-permeable channels, and has the potential for high-throughput
      functional analysis of single channels.

PMID- 14572809
TI  - Do we know the absolute values of intracellular free calcium concentration?
AB  - More than 20 years ago, it was shown that the addition of EGTA increases the
      affinity of the plasma membrane Ca2+ pump for Ca2+ by an order of magnitude. The
      left-hand shift of Ca2+-dependencies in the presence of EGTA has been also
      documented in studies of the sarcoplasmic reticulum Ca2+ pump, mitochondrial Ca2+
      transporter as well as Ca2+-binding by calmodulin and troponin C. These data
      allow us to hypothesise that this effect is caused by an admixture of di- and
      trivalent cations possessing high affinity for EGTA and interacting with Ca2+
      transporting and binding proteins. Here, we propose that polyvalent cations
      affect the estimation of absolute values of free intracellular Ca2+
      concentration. Indeed, EGTA sharply increases the apparent affinity of the
      fluorescent Ca2+ indicators quin-2 and fluo-3 for Ca2+. The impact of polyvalent
      cations on Ca2+ measurement was further confirmed by the study showing the high
      sensitivity of Ca2+-induced fluo-3 fluorescence to Mn2+, Fe2+, Cu2+, and Co2+
      seen in the absence of EGTA.

PMID- 14572811
TI  - Management of hereditary angioedema: a Canadian approach.
AB  - C1 esterase inhibitor (C1-INH) deficiency is a rare disorder that lacks consensus
      for diagnosis therapy and management. Recognizing that Canada is behind the
      European approach to this disorder, we have formed the Canadian Hereditary
      Angioedema Society (CHAES)/Societe d'angioedeme hereditaire du Canada (SAHC) to
      foster knowledge of this disorder in Canada and to advance care of patients with
      this disorder in Canada. We here present a review of treatment of this disorder
      in Canada including prevention of angioedema events and use of replacement
      therapy and present an algorithm for diagnosis therapy and management of C1-INH
      deficiency in Canada for discussion at our International Conference on Hereditary
      Angioedema to be held in Toronto, Canada, October 24th to 26th, 2003.

PMID- 14572810
TI  - The pathogenesis of hereditary angioedema.
AB  - Hereditary angioedema (HAE), which is characterized by episodic localized
      angioedema of the skin or mucosa, results from heterozygous deficiency of the
      plasma protease inhibitor, C1 inhibitor (C1INH). The most obvious biologic role
      of C1INH, therefore, is prevention of excessive vascular permeability. A variety
      of data indicate that this role is primarily a product of regulation of the
      contact system proteases, factor XIIa and plasma kallikrein. The C1INH deficient
      mouse, although it does not have episodes of cutaneous angioedema, does have
      increased vascular permeability which is reversed by treatment with C1INH, with
      the plasma kallikrein inhibitor, DX88, and with the bradykinin 2 receptor (Bk2R)
      antagonist, Hoe140. In addition, mice deficient in both C1INH and the Bk2R do not
      have increased vascular permeability. These analyses strengthen the argument that
      angioedema is mediated by bradykinin. This mouse also provides a system to test
      new potential therapeutic approaches. In addition to its role in the regulation
      of vascular permeability, C1INH also is an important modulator of inflammatory
      responses via regulation of activation of both the contact and the complement
      systems, and very likely via activities unrelated to protease inhibition.

PMID- 14572812
TI  - Estrogen-dependent inherited angioedema.
AB  - Classic forms of hereditary angioedema are characterized clinically by recurrent
      episodes of angioedema, biochemically by reduced C1 inhibitor level and/or
      function, and genetically by a heterogeneous group of mutations in the C1
      inhibitor gene that have an autosomal dominant mode of transmission. Androgens
      and estrogens have significant clinical effects in patients with hereditary
      angioedema, and tend to have antagonist effects of the levels of C1 inhibitor
      protein. Androgens increase the levels of C1 inhibitor protein, reduce attacks of
      angioedema, and thus are an important therapy for patients. The mechanisms by
      which the sex steroid hormones achieve these effects are not understood. The
      recent recognition of a novel estrogen-dependent form of angioedema may offer
      important insights into the mechanisms by which the sex hormones exert their
      effects, and the pathogenesis and treatment of both estrogen-dependent and
      classic forms of hereditary angioedema.

PMID- 14572813
TI  - How do we treat patients with hereditary angioedema.
AB  - Hereditary angioedema (HAE) is due to the inherited deficiency of C1-Inhibitor
      (C1-Inh). When specific treatment was not available, the mortality rate for this
      disease was as high as 50% and the disability up to 100-150 days per year
      (Agostoni and Cicardi, Hereditary and acquired C1-inhibitor deficiency:
      biological and clinical characteristics in 235 patients). Such a worrying
      scenario dramatically improves upon appropriate treatment. Nevertheless, the
      disease still frequently goes undiagnosed or misdiagnosed as an allergic
      condition. Both circumstances prevent patients from receiving drugs that could
      save and/or improve the quality of their life. The interest of our group for
      patients with HAE goes back to the early seventies. Since that time, 441 such
      patients have been examined and treated at our department; 403 are still actively
      followed. Here we present our experience on the treatment of HAE.

PMID- 14572814
TI  - The Hungarian HAE experience.
AB  - The Hungarian HAE Center was established in 1994, in Budapest. Assignments of the
      Center include diagnostic work-up of patients with angioedema; developing
      national guidelines for the recognition, treatment of patients with HAE;
      maintaining the registry, patient education, supply patients with info-card and
      C1-INH concentrate, follow-up of patients, telephone 'hot-line' service, under-
      and postgraduate education as well as pursues scientific activities. Established
      in 1996, the Hungarian HAE Patients' Association a foundation to support HAE
      patients; and a Hungarian HAE website. Hungarian HAE Working Group is the main
      organizer of the European C1-INH Deficiency Workshops to be held at two-year
      intervals from 1999.

PMID- 14572815
TI  - Sudden upper airway obstruction in patients with hereditary angioedema.
AB  - Hereditary angioedema (HAE) is clinically characterized by recurrent and self
      limiting skin, intestinal, and life-threatening laryngeal edema. This study
      describes the age at which laryngeal edema first occurred, the time between onset
      and full development, and the effectiveness of therapy and prophylaxis in 123 HAE
      patients. 61 (49.7%) patients experienced a total of 596 laryngeal edema
      episodes. The ratio of laryngeal edema episodes to skin swellings and abdominal
      pain attacks was approximately 1:70:54 in patients who had laryngeal edema. The
      mean (SD) age at the first laryngeal edema was 26.2 (15.3) years. Nearly 80% of
      the laryngeal edemas occurred between age 11 and 45. The mean interval between
      onset and maximum development of laryngeal edema was 8.3 hours. A total of 354
      laryngeal edemas cleared spontaneously without treatment and 208 laryngeal edemas
      were successfully treated with C1 inhibitor concentrate. Despite long-term
      prophylactic treatment with danazol, 6 patients developed subsequent laryngeal
      edemas. Laryngeal edema may occur at any age, although young adults are at
      greatest risk. In adults, the interval between onset of symptoms and acute risk
      of asphyxiation is usually long enough to allow for use of appropriate emergency
      procedures. It is essential to instruct patients and their relatives about the
      first signs of laryngeal edemas and the necessary procedures to follow.

PMID- 14572816
TI  - Diagnosis and management of hereditary angioedema: an American approach.
AB  - Hereditary angioedema (HAE) is an autosomal dominant disease characterized by
      recurrent episodes of angioedema, and caused by a deficiency of the plasma
      protein C1 inhibitor. HAE attacks carry a substantial risk of morbidity or even
      mortality, making it imperative that the correct diagnosis be established and an
      appropriate management plan be in place. This report reviews the current
      diagnostic and therapeutic approaches available in the United States. Areas in
      which the diagnostic or therapeutic tools are deficient are discussed, and the
      prospects for improved therapeutic modalities highlighted.

PMID- 14572817
TI  - Safety and efficacy of pasteurized C1 inhibitor concentrate (Berinert P) in
      hereditary angioedema: a review. jean.de.serres@aventis.com.
AB  - BACKGROUND: Hereditary angioedema caused by C1 inhibitor deficiency can be life
      threatening. Acute exacerbations are treated with intravenous purified,
      pasteurized C1 esterase inhibitor concentrate at doses of 500-1000 IU. METHODS:
      We reviewed the literature about safety and efficacy of the C1 inhibitor
      concentrate used in Canada (Berinert P) or relevant to it. RESULTS: Post
      marketing experience since 1985 is reassuring. There were few adverse events and
      no transmission of infection with the pasteurized product. A number of case
      reports, retrospective studies and few randomized or non-randomized prospective
      studies have shown good efficacy measured as clinical resolution of symptoms or
      in time to resolution, time to relief or time to improvement. CONCLUSIONS: There
      are numerous observational studies showing good efficacy and safety and a long
      post-marketing experience although few randomized placebo-controlled trials.

PMID- 14572818
TI  - DX-88 and HAE: a developmental perspective.
AB  - An example of an approach to the developmental philosophy of novel recombinant
      products is explored by using the exemplar of Hereditary Angioedema (HAE). Plasma
      kallikrein is believed to be an important mediator of angioedema in patients with
      genetic deficiency of C1 esterase inhibitor (HAE patients). DX-88, a novel Kunitz
      domain produced by phage display (a powerful method of generating novel binders
      to potentially therapeutic targets), is a potent and selective inhibitor of
      plasma kallikrein which in early clinical studies demonstrates a useful
      efficacy/safety ratio in the treatment of acute attacks of HAE.

PMID- 14572819
TI  - Protease inhibitors in the treatment of hereditary angioedema.
AB  - Deficiency of C1 Inhibitor leads to unopposed activation of complement, with
      localized, unpredictable, and sometimes life-threatening attacks of angioedema.
      Treatment with plasma-derived C1 Inhibitor rapidly aborts attacks, and may be
      lifesaving, but is expensive, requires use of a pooled blood product, may need to
      be repeated and may not be effective in autoantibody mediated angioedema. The
      antifibrinolytic agents aprotinin, tranexamic acid, and epsilon-aminocaproic acid
      are useful for prophylaxis and treatment of angioedema, likely by inhibiting
      plasmin. Specific drugs to replace the deficient C1 Inh have not been reported.
      The kallikrein inhibitor DX-88 (Dyax) has received orphan drug status in Europe
      and is undergoing clinical trial in Europe and the USA.

PMID- 14572820
TI  - Tissue archives to track blood borne pathogens in people receiving blood
      products.
AB  - Tissue banks for surveillance of pathogens, research and transplantation have
      been established in a variety of settings, and following a variety of guidelines.
      There are significant and changing ethical, moral, and legal issues in the
      development and use of such archives. The Association of Hemophilia Clinic
      Directors of Canada has established an archive of blood samples to test for known
      and emerging blood borne pathogens, and known and emerging blood clotting genes.
      Key to the development of the tissue bank was the consent process for sample
      collection and handling, the establishment of standard operating procedures for
      the handling of samples and data, and the establishment of an oversight board.

PMID- 14572821
TI  - Safety as perceived by wheelchair-seated passengers in special transportation
      services.
AB  - The aim of this study was to gain a better understanding of, and to help form a
      more complete picture of, the perceived safety of wheelchair-seated passengers
      using special transportation services (STS). A questionnaire was sent out and
      completed by 801 respondents in five Swedish regions. Additional information was
      acquired by means of 15 subsequent in-depth interviews. It was found that 5%
      reported personal incident-related injuries during the period that they had been
      eligible for STS. Injuries were most likely to occur during normal driving, but
      the passengers were also exposed to risks during boarding and alighting
      procedures. Nevertheless, 80% of the passengers were basically satisfied with the
      degree of safety. A large majority (97%) reported that they always use tie-down
      systems, and 78% always use safety belts. These results indicate that, despite
      general satisfaction with the STS system as such, malfunction of the existing
      safety equipment is a problem, since safety is especially critical for STS
      passengers-a vulnerable road-user group with few alternative travel modes.
      Therefore, there is a need for wheelchair tie-down and occupant restraint systems
      (WTORS) that are easier to handle by the operators and more suitable for the
      passengers and their wheelchairs. A low-floor vehicle concept might also reduce
      injury risks related to boarding and alighting procedures.

PMID- 14572822
TI  - Measuring transport injuries in a developing country: an application of the
      capture-recapture method.
AB  - The purposes of this study are to provide an estimation of the incidence of
      transport injuries in a defined local community in Nicaragua by using the capture
      recapture method, and to compare results using this method when data at different
      levels of severity are utilized. Two sources of injury data were used to monitor
      injuries: hospital data (inpatient and outpatient) and traffic police records.
      Characteristics available for matching included name, age, sex, and date of
      occurrence. The methodology of capture-recapture was used to estimate the
      ascertainment degree of both sources of data and the estimate mortality and
      incidence rates. Estimates were calculated both when all hospital data were taken
      into account (inpatient and outpatient combined) and when only inpatient records
      were matched against police records.First, including police records and all
      hospital data, the mortality and morbidity estimates were 35.5/100000 and
      43.7/1000 per year, respectively. Second, when outpatients were excluded from the
      analysis, the corresponding estimates were 28.6/100000 and 7.5/1000,
      respectively. In non-fatal cases, the ascertainment-corrected coverage through
      police records was 2.6% and through hospital surveillance 19.0% when both
      inpatients and outpatients were included. In fatal cases, the corresponding rates
      were 56.1 and 22.8%, respectively. The combined data set pointed out pedestrians
      and cyclists as the main risk groups. Most fatalities were due to head injuries.
      Our results show that neither police records nor hospital records nor the
      aggregate database provided acceptable coverage of transport-related injuries.
      Combining police and hospital data by means of capture-recapture analysis
      produces more valid estimates, but caution must be given to the issue of severity
      heterogeneity between the two sources.

PMID- 14572823
TI  - Neck strains and sprains among motor vehicle occupants-United States, 2000.
AB  - CONTEXT: Motor vehicle (MV)-related injury is a leading cause of death and
      emergency department visits in the US. Information has been limited regarding the
      magnitude and types of injuries suffered by the survivors of MV crashes.
      OBJECTIVE: To estimate the incidence and patterns of neck strain/sprain injury
      among MV occupants treated in US hospital emergency departments. DESIGN AND
      PARTICIPANTS: Descriptive epidemiologic analysis of persons treated at a
      stratified, probability sample of US hospital emergency departments from 1 July
      to 31 December 2000. SETTING: US. MAIN OUTCOME MEASURES: Annualized national
      estimates of number and rate of neck strain/sprain injury among MV occupants
      overall and by patient's age and sex. Rates were calculated per 100,000
      population as well as per billion person miles traveled. RESULTS: In 2000, an
      estimated 901,442 (95% CI 699,283-1,103,601) persons with neck strain/sprain
      injury were treated in US hospital emergency departments. For MV occupants, neck
      strain/sprain was the most frequent type of injury, comprising 27.8% of all
      injuries to MV occupants treated in emergency departments that year. The
      incidence (per 100,000 population) of neck strain/sprain was significantly lower
      in younger children and peaked in the 20-24-year age group. The incidence (per
      billion person miles traveled) peaked in the 15-19-year age group. Females tended
      to have a higher incidence of emergency department-treated neck strain/sprain
      than males. CONCLUSIONS: Neck strain/sprain is the most common type of injury to
      MV occupants treated in US hospital emergency departments. Based on emergency
      department visits, these estimates suggest that the problem of neck injury may be
      larger than has been previously demonstrated using other surveillance tools.
      Further research is needed to determine contributory factors and prevention
      measures to reduce the risk of neck injury among MV occupants especially among
      those at higher risk such as females, older teenagers and young adults.

PMID- 14572824
TI  - Effectiveness of customized Victim Impact Panels on first-time DWI offender
      inmates.
AB  - This study investigates the effectiveness of a customized Victim Impact Panel
      (VIP) on reducing 'driving while impaired' recidivism, alcohol consumption and
      drinking and driving behavior. The study was conducted at a 28-day
      Detention/Treatment Program in a largely rural county in northwestern New Mexico.
      Study participants were randomly assigned to attend or not attend a VIP while
      participating in the program for court-defined first-time driving while
      intoxicated (DWI) offenders. There were no significant differences between the
      two groups on alcohol consumption, drinking and driving behavior, or recidivism
      within 2 years. These findings support the findings of other studies that VIPs do
      not produce a differential benefit with regards to recidivism of those convicted
      as a first-time DWI offenders.

PMID- 14572825
TI  - Road traffic injuries in an urban area in Mexico. An epidemiological and cost
      analysis.
AB  - The objective of this study was to do an epidemiological and costs analysis of
      the impact of road traffic injuries on the demand for emergency room services at
      hospitals located in the city of Cuernavaca, Mexico. The studied population
      included injured people who demanded medical attention at the emergency room for
      injuries due to events in public places, occurring between February and April
      2001. Trained interviewers collected the data at the emergency room, 24h a day.
      The statistical analysis included simple and bivariate analysis using chi(2) odds
      ratio (OR), and a confidence interval of 95%. The costs analysis included the
      expenses during the process of searching for and finding care for injuries. There
      were 433 injured people, 233 (54%) were victims of road traffic accidents, 72% of
      crashes, and 28% were injured pedestrian and cyclists. Variables associated with
      the demand of emergency care due to road traffic injuries in comparison with
      other accidents, were: severity of injuries (OR 2.60, CI 1.44-4.71), and thorax
      injury (OR 4.64, CI 1.03-20.89). Pedestrians had higher costs for health care and
      80% of them had to pay out-of-pocket (P<0.05). Differences between patients
      injured by crashes or as a pedestrian, were: age under 14 years (OR 5.9, CI 2.5
      13.9), being unemployed (OR 2.1, CI 1.20-3.96), and being an elementary school
      student (OR 13.9, CI 3.08-63.13). The present study is, so far, the only one in
      Mexico to include an epidemiological and costs analysis in approaching the
      problem of road traffic injuries. Similar methods must be used, especially in
      developing countries, to reduce this important public health problem.

PMID- 14572826
TI  - Motor ability: protective or risk for school injuries?
AB  - The study aims were to assess the independent contribution of motor ability to
      the incidence of school injuries. The study included 2057 pupils in grades 3-6 of
      primary schools in a city in the north of Israel. A surveillance system gathered
      information about injuries that occurred on school premises or during school
      related activities and required medical treatment or caused limitation of usual
      activities. Children provided information on sensation seeking, self-appraisal of
      health, academic performance, physical activity, and dominant hand;
      anthropometric measurements and motor ability tests were performed. The incidence
      of injury events was 4% (95% CI=3.2-5.0). Injuries increased with increased
      balance and agility, but there were no differences according to reaction time. No
      other study variables were associated with the incidence of injuries. Our
      findings of an increase in the incidence of injuries with better motor ability
      may express differences in exposure to risk situations between children with
      better and poorer motor abilities.

PMID- 14572827
TI  - The influence of alcohol, age and number of passengers on the night-time risk of
      driver fatal injury in New Zealand.
AB  - Breath alcohol measurements and other data collected at randomly selected
      roadside sites were combined with data on fatally injured drivers in crashes
      occurring on the same weekdays and times (Friday and Saturday nights) at
      locations matched by the size of the nearest town. A logistic model was fitted to
      these data for the years 1995-2000 to estimate the effects of alcohol, driver's
      age and the influence of passengers carried on the risk of driver fatal injury in
      New Zealand. The estimated risks increased steeply with increasing blood alcohol
      concentration (BAC), closely following an exponential curve at levels below about
      200mg/dl (i.e. 0.2%) and increasing less than exponentially thereon. The model
      fitted to data for drivers under 200mg/dl showed that risks at all BAC levels
      were statistically significantly higher for drivers aged under 20 (over five
      times) and for drivers aged 20-29 (three times) than for drivers aged 30 and
      over. Further, controlling for age and BAC level, driving with a single passenger
      was associated with approximately half the night-time risk of driver fatal injury
      relative to driving either solo or with two or more passengers. According to a
      recent travel survey, the types of passengers carried at the times of night and
      days of week studied appear to differ significantly from the types of passengers
      carried generally, which may lead to different passenger effects on driver
      behaviour. The high relative risk of teenage drivers means that they reach high
      risk levels commonly regarded as unacceptable in the field of road safety even at
      their current legal limit of 30mg/dl, particularly when more than one passenger
      is carried in the car.

PMID- 14572828
TI  - Characteristics of low speed accidents with buses in public transport: part II.
AB  - A number of accident characteristics of bus crashes are analyzed in relation to
      each other using data from 2237 accident involvements in the city of Uppsala
      (Sweden) during the years 1986-2000. The breakdown of accidents into sub
      categories show, for example, that injury was common in intersection accidents,
      that bus stops present large risk for shunts and side contacts, while single
      vehicle accidents were seldom preceded by the loss of control or a skid. The
      treatment of accident data is discussed in terms of methodology, statistics and
      data reduction strategies.

PMID- 14572829
TI  - Pedestrian injuries and vehicle type in Maryland, 1995-1999.
AB  - Pedestrian deaths constitute the second largest category of motor vehicle deaths
      in the US. The present study examined how pedestrian injury is associated with
      vehicle type, while controlling for vehicle weight and speed.Police, trauma
      registry, and autopsy data were linked for injured pedestrians. Logistic
      regression analyses were performed to control for vehicle weight and speed.
      Outcomes included pedestrian mortality, injury severity score, and injuries to
      specific body regions. Compared to conventional cars, pedestrians hit by sport
      utility vehicles and pick-up trucks were more likely to have higher injury
      severity scores (odds ratio=1.48; 95% confidence interval: 1.18-1.87) and to die
      (odds ratio=1.72; 95% confidence interval: 1.31-2.28). These relationships
      diminished when vehicle weight and speed were controlled for. At lower speeds,
      pedestrians struck by sport utility vehicles, pick-up trucks, and vans were
      approximately two times as likely to have traumatic brain, thoracic, and
      abdominal injuries; at higher speeds, there was no such association. The overall
      increased danger sport utility vehicles and pick-up trucks present to pedestrians
      may be explained by larger vehicle masses and faster speeds. At slower speeds
      being hit by sport utility vehicles, and pick-up trucks, and vans resulted in
      specific injuries, indicating that vehicle design may contribute to different
      injury patterns.

PMID- 14572830
TI  - The stability of driver acceleration behavior, and a replication of its relation
      to bus accidents.
AB  - The reliability over time of a method for measuring driver acceleration behavior
      was tested on bus drivers in regular traffic. Also, a replication of an earlier
      finding of a correlation between driver acceleration behavior and accident
      frequency for the individual drivers was made. It was found that the split-half
      correlation is probably around 0.50 for the mean (of accelerations) of a 30-min
      drive, and similar for the test-retest of 2.5h measured about a month apart. With
      such reliability, the sample was probably too small to reliably determine any
      association with accidents, but some significant correlations were found. Some
      ways of holding constant the differences in exposure and driving environment were
      tried with mixed success. Alternate ways of analyzing the data and several
      methodological problems were briefly discussed. It was concluded that the
      measurements of acceleration behavior, for bus drivers, are fairly reliable over
      at least a few months. However, some strange discrepancies between samples make
      all interpretations concerning the link to accidents tentative.

PMID- 14572831
TI  - Injury and risk-taking behavior-a systematic review.
AB  - There is a substantial body of work in the scientific literature discussing the
      role of risk-taking behavior in the causation of injury. Despite the quantity of
      diverse writings on the subject most is in the form of theoretical commentaries.
      This review was conducted to critically assess the empirical evidence supporting
      the association between injury and risk-taking behavior. The review found six
      case-control studies and one retrospective cohort study, which met all the
      inclusion criteria. Meta-analysis was not possible due to the diversity of the
      independent and outcome variables in each of the studies reviewed. Overall the
      review found that risk-taking behavior, however it is measured, is associated
      with an increased chance of sustaining an injury except in the case of high
      skilled, risk-taking sports where the effect may be in the other direction.
      Drawing specific conclusions from the research presented in this review is
      difficult without an agreed conceptual framework for examining risk-taking
      behavior and injury. Considerable work needs to be done to provide a convincing
      evidence base on which to build public health interventions around risk behavior.
      However, sufficient evidence exists to suggest that effort in this area may be
      beneficial for the health of the community.

PMID- 14572832
TI  - Improvements in medical care and technology and reductions in traffic-related
      fatalities in Great Britain.
AB  - Great Britain has one of the lowest levels of traffic-related fatalities in the
      industrialized world with a current total of about 3500 fatalities per year.
      Large reductions have occurred over the last 20-30 years and the government has
      targets of achieving another 40% reduction by 2010. This paper analyzes some of
      the factors that have been statistically significant in helping to achieve those
      reductions with a focus on improvements in medical care and technology. Using a
      cross-sectional time-series of regional data a fixed effects negative binomial
      (NB) model is estimated which includes three proxies of medical care and
      technology changes. These are the average length of inpatient stay in the
      hospital, the per-capita level of National Health Service (NHS) staff, and number
      of people per-capita waiting for hospital treatment. All are statistically
      significant with the expected sign showing that improvements in medical
      technology have reduced total fatalities with less of an impact from changes in
      medical care. Other variables are also found to be significant, including the
      percent of elderly people in the population, per-capita expenditure on alcohol,
      motorway capacity, and average vehicle age. The latter shows a surprisingly
      unexpected effect, with more older vehicles in a region leading to fewer
      fatalities. Models evaluating effects on serious and slight injuries are also
      estimated and serve to confirm the expected effects of medical care and
      technology.

PMID- 14572833
TI  - Effects on road safety of new urban arterial roads.
AB  - This paper presents an evaluation of the effects on road safety of new urban
      arterial roads in Oslo, Norway, and a synthesis of evidence from similar studies
      that have evaluated the safety effects of new urban arterial roads in other
      cities. A before-and-after study was made of four urban arterial road projects in
      Oslo. The study controlled for general accident trends in Oslo and for regression
      to-the-mean. A statistically non-significant reduction of 9% in the number of
      injury accidents was found for all four projects combined. The effects on safety
      of new urban arterial roads were found to vary, depending on whether a new
      arterial road was built, or an existing arterial road upgraded by means of lane
      additions and reconstruction of junctions to interchanges. New arterial roads
      tend to induce more traffic, which tends to offset the benefits of a lower
      accident rate on the new roads. The results for other cities are very consistent
      with those for Oslo. For a total of seven cases in which new arterial roads were
      built, a statistically non-significant reduction of 1% in the number of injury
      accidents was found. Two cases that involved lane additions and converting at
      grade junctions to interchanges resulted in a mean accident reduction of 51%,
      which was highly significant. On the average, the nine arterial road projects
      from which evidence was summarised resulted in a net induced traffic of 16%, and
      a net reduction in accident rate (accidents per million vehicle kilometres) of
      18%. These effects almost cancel each other, leading to a very small net change
      in the expected number of accidents.

PMID- 14572834
TI  - The alcohol-related accident risk in Germany: procedure, methods and results.
AB  - This paper presents the first reliable estimation of the alcohol-related accident
      risk in Germany by comparing a representative sample of accidents to a
      representative sample of trips not leading to a crash. The information about the
      trips was taken from the German Roadside Survey 1992-1994 (n=9087) conducted in
      Unterfranken, part of Bavaria. These data were weighted according to a
      representative study of driving in Germany (KONTIV 89). The accident study
      comprises a representative sample of accidents in Unterfranken in 1993 (n=1968).
      Relating accident risk to BAC, the global risk function indicates an exponential
      increase of accident risk for BACs above 0.05%. Controlling for correlating
      factors leads to an overall lower estimation with, however, the same structure,
      indicating that alcohol is consumed by drivers in circumstances which further
      increase the risk introduced by alcohol. Analyzing the attributable risk (AR)
      shows that about 12% of all accidents are attributable to alcohol. Over 96% of
      these happen with BACs of 0.05% and above. Thus, measures aimed at reducing the
      alcohol-related accident risk must focus on larger BACs, especially of 0.08% and
      above.

PMID- 14572835
TI  - Inequalities in child mortality in Mozambique: differentials by parental socio
      economic position.
AB  - This study investigates the relation between socio-economic parental position
      (education and occupation) and child death in Mozambique using data from the
      Mozambican Demographic and Health Survey carried out between March and July 1997.
      The analysis included 9142 children born within 10 years before the survey. In
      spite of the Western system of classification used in the study, the results
      partly showed a parental socio-economic gradient of infant and child mortality in
      Mozambique. Father's education seemed to reflect the family's social standing in
      the Mozambique context, showing a strong statistical association with
      postneonatal and child mortality. However, maternal education as a measure of
      socio-economic position was not statistically significantly associated with child
      mortality. This finding may partly be explained by the extreme hardships
      experienced by the country (civil war and natural disasters) and the
      implementation of the Economic Structural Adjustment Programme that have also
      affected the health of women and their children during the years covered by this
      study. Other measures of socio-economic position applicable to the rural African
      setting should be investigated.

PMID- 14572836
TI  - Does stage at diagnosis influence the observed relationship between socioeconomic
      status and breast cancer incidence, case-fatality, and mortality?
AB  - Historically, lower socioeconomic status (SES) has been reported to be associated
      with decreased breast cancer incidence and mortality and increased case-fatality,
      although recent trends in breast cancer screening and treatment may alter these
      relationships. This study assessed the associations between SES and breast cancer
      incidence, case-fatality, and mortality by stage of disease at diagnosis using
      recent data in the United States. Breast cancer incidence and survival data from
      the Surveillance, Epidemiology, and End Results (SEER) tumor registry for black
      and white women aged 55 and above were linked to county level SES and population
      data based on place of residence. Poisson regression was used to calculate age
      adjusted relative rates associated with SES levels and breast cancer incidence,
      case-fatality, and mortality. As SES decreased, localized breast cancer incidence
      rates decreased, while incidence rates of distant disease increased. Five-year
      localized and regional breast cancer case-fatality rates increased as SES
      decreased. Localized breast cancer mortality rates decreased as SES declined,
      whereas regional breast cancer mortality rates tended to increase. These results
      confirm some previously reported findings and suggest that associations between
      lower SES and lower localized breast cancer mortality rates are influenced mainly
      by underlying associations between SES and localized breast cancer incidence,
      whereas regional breast cancer mortality rates appear to reflect the underlying
      association between SES and regional case-fatality rates.

PMID- 14572837
TI  - Occupational class and physical activity among Japanese employees.
AB  - We examined the distribution of physical activity among different occupations in
      Japan. A questionnaire was sent to full-time employees at nine companies in Japan
      between 1996 and 1998, with an average response rate of 85.2%. Data from 20,654
      respondents (17,637 male and 3017 female) were analyzed. We classified the
      occupations into eight groups according to the International Standard
      Classification of Occupations (1988). Daily energy expenditure, weekly physical
      activity, and monthly leisure-time physical activity (LTPA) were measured using a
      physical activity questionnaire and some additional questions. In males, LTPA was
      significantly different among occupations, with clerks having greater physical
      activity than managers and blue-collar workers (P<0.001). The pattern was similar
      even after adjusting for education, age, and working hours. In females, the
      difference among occupations was not clear. The distribution of LTPA among
      occupations exhibits a "barrel-shape" in Japan. It was higher for intermediate
      class occupations such as clerks, which was in agreement with a lower coronary
      heart disease mortality observed in intermediate class occupations among Japanese
      male employees.

PMID- 14572838
TI  - Is position in the occupational hierarchy a determinant of decline in perceived
      health status?
AB  - This study examines the extent to which position in the occupational hierarchy is
      predictive of declines in perceived health status over a 48 month period in a
      representative sample of the Canadian labor force. We hypothesized that the
      proportion of workers reporting a decline in health status would be greater among
      persons in lower position in the occupational hierarchy, and that these
      differences in risk would primarily be explained by characteristics of the
      psychosocial work environment and secondarily by the baseline prevalence of
      adverse health behaviors. The study cohort was defined as labor force
      participants aged 18-64 who reported good, very good or excellent health in the
      1994 baseline wave of Canada's National Population Health Survey and who
      participated in the 1998 follow-up survey. Between 1994 and 1998, 16.6% of labor
      force participants reporting excellent, very good or good health status at
      baseline reported a decline in perceived health status. For men, the age-adjusted
      odds of decline in perceived health status were 1.80 (95% CI: 1.24-2.63) and 1.74
      (95% CI: 1.19-2.54) for the two lowest occupational classes relative to the
      highest occupational class. There was no association between position in the
      occupational hierarchy and the prospective risk of health status decline for
      women. For men, the association between position in the occupational hierarchy
      and decline in perceived health status was moderately reduced but remained
      statistically significant following adjustment for baseline health, health
      behaviors and psychosocial work exposures. Adjustment for household income did
      not alter these findings. When stratified by gender, position in the occupational
      hierarchy was associated with the prospective risk of health status decline for
      men but not for women. Among men, the collective influence of health behaviors
      and psychosocial work exposures explained a moderate component of the decline in
      perceived health status. A more robust measurement of the characteristics of
      labor market experiences would be expected to improve understanding of the
      relationship between work and health in this sample.

PMID- 14572839
TI  - Socioeconomic gradients in health status over 29 years of follow-up after
      midlife: the Alameda county study.
AB  - Socioeconomic status is well known to be associated with inverse gradients in a
      wide range of health outcomes. Very little is known about the precise shape of
      these relationships and how they evolve through the life-course, although recent
      work has suggested steep non-linearities for mortality in samples of the entire
      population that include the very poor. We investigate the shape of gradients,
      against baseline family income, in gender-specific prevalence rates for seven
      self-reported health outcomes commonly used on surveys, in a cohort of 1190 men
      and 1302 women representative of Alameda County, California, aged 40-59 in 1965.
      Over 29 years of follow-up, four different prevalence-income gradients among
      surviving subjects are examined as this cohort has aged, in 1965, 1974, 1983 and
      1994. Virtually all the gradients are inverse, although there is no simple
      pattern of shape, or evolution of shape over time, across health outcomes.
      However, there is a consistent trend for male gradients to be distinctly more non
      linear than female gradients, such that the poorest men show disproportionately
      higher rates of ill health, based on generalized linear piecewise regression
      models, comparing the low versus high-income slopes of the gradients. However,
      sub-analyses of only those long-lived cohort members, who survived through all
      follow-ups, largely abolished the non-linearities in the male prevalence curves
      (except for "self-assessed health status" and "depression"), making them much
      more like female curves. This suggests that for all of these common forms of
      morbidity, the excess prevalence among very low income males was associated with
      elevated mortality. Confirmation of this observation must await richer data on
      other aspects of socioeconomic status in comparable cohorts, analyzed with
      similar methods.

PMID- 14572840
TI  - A review of psychosocial interventions in infertility.
AB  - Counselling has been strongly recommended by numerous governmental, medical and
      community associations to help infertile people. The purpose of this review was
      to determine whether psychosocial interventions improved well-being and pregnancy
      rates, and to identify the kinds of interventions that were most effective. A
      systematic search identified all published and unpublished papers in any language
      and any source that (1) described a psychosocial intervention and (2) evaluated
      its effect on at least one outcome measure in an infertile population. A total of
      380 studies met the first criteria but only 6.6% (n=25) of these were independent
      evaluation studies. Analysis of these studies showed that psychosocial
      interventions were more effective in reducing negative affect than in changing
      interpersonal functioning (e.g., marital and social functioning). Pregnancy rates
      were unlikely to be affected by psychosocial interventions. It was also found
      that group interventions which had emphasised education and skills training
      (e.g., relaxation training) were significantly more effective in producing
      positive change across a range of outcomes than counselling interventions which
      emphasised emotional expression and support and/or discussion about thoughts and
      feelings related to infertility. Men and women were found to benefit equally from
      psychosocial interventions. Directions for future research on the evaluation of
      psychosocial interventions are discussed.

PMID- 14572841
TI  - A symptom perception approach to common physical symptoms.
AB  - This study investigated variables assumed to influence the symptom perception
      process, as well as the sociodemographic variables of age, gender and
      socioeconomic status, regarding their relation to common physical symptoms. In
      addition, it ascertained the predictors of two symptom measurement methods
      (prospective and retrospective). A group of 152 men and women completed a
      standardized interview as well as several questionnaires and kept a diary for 4
      weeks. Path analyses showed an adequate data fit irrespective of symptom measure.
      Two main routes to both prospectively and retrospectively measured physical
      symptoms were found: one from more negative affectivity via a stronger tendency
      to selective attention and the other from unemployment or a higher number of
      chronic diseases via a lower quantity of external information. The effect of age
      on physical symptoms was mediated by the number of chronic diseases and the
      tendency to selectively attend to bodily sensations. The effects on physical
      symptoms proved to depend partly on the method of symptom measurement and varied
      according to the mediating role of negative mood and the tendency to make
      psychological attributions. Overall, this study highlights the importance of
      estimating the independent contribution of variables to the experience of common
      physical symptoms in a comprehensive model while taking into account the method
      of symptom measurement. In addition, it demonstrates the usefulness of a symptom
      perception approach for further study.

PMID- 14572842
TI  - Toward understanding youth suicide in an Australian rural community.
AB  - Australia has one of the highest rates of youth suicide in the western world,
      especially among rural men. This paper discusses the social construction of this
      issue in Australia and explores the issue through interviews with 30 young people
      and 12 key informants from a rural town in NSW. Findings suggest that young
      people struggle to deal with conflict in social relationships, that community
      discourses shape young people's understandings and that suicide is talked about
      in reference to depression. Implications for youth suicide prevention in
      Australian rural communities are discussed.

PMID- 14572843
TI  - Supplying emergency contraception via community pharmacies in the UK: reflections
      on the experiences of users and providers.
AB  - This paper discusses findings from an evaluation of a scheme to provide free
      emergency hormonal contraception (EHC) via community pharmacies in the North-West
      of England. Drawing on interview data with pharmacists taking part in the scheme
      and focus groups with users, we tentatively suggest that the scheme was largely
      well received. The benefits of the service, cited by both pharmacists and users,
      included enhanced access to EHC, at times when it was needed, and at no cost to
      the user. In particular, users noted a welcome absence of judgmental attitudes
      when accessing the service. Pharmacists too were positive about the service, not
      least because they believed that it conferred enhanced professional status.
      However, both users and pharmacists had a number of major concerns about the
      schemes, centring on the potential for misuse, changes in contraceptive behaviour
      and the impact on sexually transmitted infections. We conclude that more research
      is needed to explore these issues.

PMID- 14572844
TI  - Family caregiver perspective-taking and accuracy in estimating cancer patient
      symptom experiences.
AB  - As family caregivers assume more prominent roles in the provision of home care to
      persons with serious illness, investigators must test the effectiveness of novel
      interventions to facilitate family caring for cancer patients. This article is
      based on results derived from a larger study carried out in Canada that was
      designed to compare 98 advanced cancer patient and family caregiver perceptions
      of 32 patient symptom experiences as captured by the Memorial Symptom Assessment
      Scale. We examined two main questions: (1) whether "natural" family caregivers'
      perceptions of patient lack of energy and worrying are more closely related to a
      self- or patient-oriented viewpoint and (2) whether induced "imagine-patient"
      perspective-taking can assist caregivers to achieve better perceptual accuracy.
      The caregiver's natural responses to neutral instructions that neither encouraged
      nor discouraged perspective-taking served as the baseline comparison with three
      other instructional sets, in which caregivers were prompted to: (1) provide a
      self-report on their own symptom experiences, (2) imagine how they would feel in
      the patient's situation (imagine-self), or (3) imagine how the patient would
      respond to his or her symptom situation (imagine-patient). Findings suggested
      that the family caregivers' natural judgments correspond most closely to what
      they do under an imagine-patient set than to what they do under any other set.
      Findings with respect to accuracy indicated that instructions to imagine the
      patient's perspective helped to prompt adjustments down from a self-oriented
      viewpoint, although definitive conclusions were precluded by difficulties with
      order effects.

PMID- 14572845
TI  - The quality of life of spouse dementia caregivers: changes associated with
      yielding to formal care and widowhood.
AB  - The focus of the study was the effect on spouse dementia caregivers of
      relinquishing care. The study used a longitudinal design, in which a group of 150
      dementia caregivers were interviewed 2 years apart (designated Time 1 and Time
      2), with data collected from both continuing caregivers and those who had
      relinquished care. The aims were to determine the extent to which changes over
      time in quality of life differed between continuing caregivers, those who had
      yielded to formal care, and those who had been widowed; and to examine whether
      change in quality of life variables was associated with time since yielding to
      formal care and time since death of the spouse. Quality of life was defined in
      terms of health status, psychological well-being, and activity participation. All
      participants were interviewed in their own homes. Three groups of participants
      were identified at Time 2: those who continued to provide care for their spouses
      (n=60); those who had yielded their caregiver role by admitting their spouses to
      permanent residential care (n=53); and those who had admitted their spouses to
      permanent institutional care, but whose spouse had then died (n=37). Different
      patterns of quality of life changes were observed between the three groups, with
      both positives and negatives associated with disengagement from the caregiving
      role. Positive changes were particularly evident in psychological well-being and
      activity participation. These findings were discussed in terms of their relevance
      for a life transitions approach to the relinquishment of caregiving.

PMID- 14572846
TI  - Causal inference from randomized trials in social epidemiology.
AB  - Social epidemiology is the study of relations between social factors and health
      status in populations. Although recent decades have witnessed a rapid development
      of this research program in scope and sophistication, causal inference has proven
      to be a persistent dilemma due to the natural assignment of exposure level based
      on unmeasured attributes of individuals, which may lead to substantial
      confounding. Some optimism has been expressed about randomized social
      interventions as a solution to this long-standing inferential problem. We review
      the causal inference problem in social epidemiology, and the potential for causal
      inference in randomized social interventions. Using the example of a currently on
      going intervention that randomly assigns families to non-poverty housing, we
      review the limitations to causal inference even under experimental conditions and
      explain which causal effects become identifiable. We note the benefit of using
      the randomized trial as a conceptual model, even for design and interpretation of
      observational studies in social epidemiology.

PMID- 14572847
TI  - Mobility limitations 1974-1991: period changes explaining improvement in the
      population.
AB  - The proportion of people with mobility limitations (difficulties with running,
      walking and stairs) decreased between 1968 and 1991 in the Swedish population
      aged 18-75. The distribution of predictors of late life morbidity, e.g., social
      class, health behaviour and childhood conditions, also changed during this
      period. This study explored whether the changes in these predictors over time
      were related to the decrease in the proportion of the population with mobility
      limitations. In two nationally representative interview samples (n=4468) from
      1974 and 1991 of persons aged 45-71 the odds for limitations were cross
      sectionally compared in ordered logistic regression models. In addition,
      predictors for the mobility outcome in 1974 were collected from an earlier 1968
      survey and predictors for the 1991 outcome were collected from 1981. In 1974 the
      odds for limitations in the population was 50% higher than in 1991. Had the
      population composition regarding social class and housewives in 1991 been
      identical to 1974, the odds for limitations would have been similar in 1974 and
      1991. Period improvement in social classes with poorer mobility also contributed
      to the overall period improvement. Health behaviours were examined as possible
      mediating factors. The increase of physically active people between 1968 and 1974
      was related to the period improvement in mobility between 1974 and 1991. Smoking
      showed an increased association with mobility limitations during the period,
      indicating that mobility improvement would have been greater if everyone had been
      a non-smoker. Results indicate how sensitive disability rates may be for cohort
      or period effects.

PMID- 14572848
TI  - Networked for change? Identifying obstetric opinion leaders and assessing their
      opinions on caesarean delivery.
AB  - The objective was to determine whether obstetric opinion leaders can be
      identified and to characterize them in terms of their demographic and
      professional characteristics and their attitudes toward caesarean delivery. In
      late 1998, we surveyed 527 obstetricians, 138 family physicians, and 80 certified
      nurse midwives (overall response rate, 57.8%) practicing in a stratified random
      sample of California hospitals with at least 1000 annual deliveries (n=52).
      Participants reported on demographic and professional characteristics and
      attitudes towards caesarean delivery; they also checked off those hospital
      colleagues from whom they had sought or would seek advice on labour and delivery.
      A composite measure of nomination frequency was used to characterize each
      respondent's degree of "opinion leadership". All analyses were corrected for the
      complex survey design. Using a nomination cutoff of 0.4 (0-1 scale), opinion
      leaders were identified in 31% of California hospitals; they were identified in
      81% of hospitals using a cutoff of 0.2. Compared with their peers in the lowest
      fifth of the nomination distribution, clinicians in the top fifth were younger
      and more likely to be male, to speak English as a first language, to practice
      obstetrics, to have a maternal-foetal medicine subspecialty, and to practice in
      higher volume hospitals (p<0.05). Regardless of discipline, opinion leaders held
      attitudes concordant with reducing the caesarean delivery rate more often than
      non-opinion leaders. However, only 48% of obstetrical opinion leaders would
      support reducing the caesarean delivery rate to levels targeted by Healthy People
      2000. In conclusion, obstetric opinion leaders could be identified in many
      California hospitals. However, they did not consistently support policies
      designed to reduce the caesarean delivery rate. The results have implications for
      the generalizability of opinion leader strategies.

PMID- 14572849
TI  - Stigma as a barrier to treatment of sexually transmitted infection in the
      American deep south: issues of race, gender and poverty.
AB  - Sexually transmitted infections (STI) occur at high rates in the US compared to
      other Western nations. Sociocultural indicators such as race and ethnicity, lower
      socioeconomic status and historically higher rates of certain diseases, such as
      syphilis, are correlated factors but do not explain fully why STI rates are
      particularly high in the American Deep South. One salient factor is the stigma
      associated with STI and its effect on screening and treatment. This paper
      presents the results of six focus group interviews that were conducted among
      mainly African-American health workers, patients and students in Alabama, USA.
      The results showed that STI-related stigma directly and indirectly affected
      willingness to be treated for STI at public health clinics. Four dimensions of
      stigma emerged: (1) Religious ideation affected how health workers felt about
      'promiscuous' patients (especially women), (2) privacy fears discouraged male
      patients from seeking treatment at local clinics, (3) racial attitudes affected
      willingness to be treated for STI and (4) Stigma transference (being "scarlet
      lettered") emerged as a potent disincentive to treatment. Partner notification
      was more likely if patients felt betrayed by a sexual partner. Further research
      is needed to clarify these stigma-related dimensions and the impact on screening,
      treatment and partner services.

PMID- 14572850
TI  - Utilization of care during pregnancy in rural Guatemala: does obstetrical need
      matter?
AB  - This study examines factors associated with the use of biomedical care during
      pregnancy in Guatemala, focusing on the extent to which complications in an
      ongoing or previous pregnancy affect a woman's decisions to seek care. The
      findings, based on multilevel models, suggest that obstetrical need, as well as
      demographic, social, and cultural factors, are important predictors of pregnancy
      care. In contrast, measures of availability and access to health services have
      modest effects. The results also suggest the importance of unobserved variables-
      such as quality of care--in explaining women's decisions about pregnancy care.
      These results imply that improving proximity to biomedical services is unlikely
      to have a dramatic impact on utilization in the absence of additional changes
      that improve the quality of care or reduce barriers to access. Moreover, current
      efforts aimed at incorporating midwives into the formal health-care system may
      need to extend their focus beyond the modification of midwife practices to
      consider the provision of culturally appropriate, high-quality services by
      traditional and biomedical providers alike.

PMID- 14572851
TI  - The continuum of patient satisfaction--from satisfied to very satisfied.
AB  - In a move towards a more informed understanding of the concept of satisfaction,
      this paper aims to explore how 30 dermatology patients describe what it meant to
      them to be either satisfied or very satisfied with their healthcare. This was
      undertaken using in-depth interviews and the findings suggest that participants
      clearly differentiated between being satisfied or very satisfied with healthcare.
      While for some participants, being satisfied with healthcare was described in
      terms of care being adequate or average, for others it meant that there were
      aspects of healthcare that could be improved, or that something was missing and
      that optimal care was not achieved. Care and management had been 'acceptable' or
      'sufficient' but not 'outstanding.' In contrast, being very satisfied with
      particular aspects of healthcare was described in ways that suggested that the
      service was not only more than adequate, but ranged from 'better than average' to
      'outstanding', i.e. optimal care had been provided. This observation of a
      'continuum of satisfaction' has specific and important implications for the
      future analysis and presentation of patient satisfaction surveys. It is suggested
      that attention to the differences between the two constructs provides a useful
      means to highlighting areas of patient concern and that researchers reporting the
      results of patient satisfaction surveys should cease to collapse them.

PMID- 14572852
TI  - Letter response to Margaret Everett (2003) "The social life of genes: privacy,
      property and the new genetics" Social Science & Medicine, 56:1.

PMID- 14572856
TI  - 4-Amino-3(2H)-pyridazinones bearing arylpiperazinylalkyl groups and related
      compounds: synthesis and antinociceptive activity.
AB  - A series of 4-amino-3(2H)-pyridazinones substituted at position 2 with
      arylpiperazinylalkyl groups and analogues were synthesized and their
      antinociceptive effect was evaluated in the mouse abdominal constriction model.
      Preliminary SARs studies were performed. Several of the novel compounds dosed at
      100 mg/kg s.c. significantly reduced the number of writhes induced by the noxious
      stimulus. Compound 12e showed 100% inhibition of writhes and was able to protect
      all the treated animals from the effect of the chemical stimulus. Subsequent dose
      response studies revealed 12e to be almost 40-fold more potent than the
      structurally related Emorfazone.

PMID- 14572857
TI  - Antituberculosis agents VIII. Synthesis and in vitro antimycobacterial activity
      of alkyl alpha-[5-(5-nitro-2-thienyl)-1,3,4-thiadiazole-2-ylthio]acetates.
AB  - A series of alkyl alpha-[5-(5-nitro-2-thienyl)-1,3,4-thiadiazole-2-ylthio]acetic
      acid esters 6a-e were synthesized and evaluated for in vitro antituberculosis
      activity against Mycobacterium tuberculosis strain H(37)Rv using the BACTEC 460
      radiometric system and BACTEC 12B medium. The antituberculosis data indicated
      that methyl, propyl, buthyl and benzyl esters showed a significant in vitro
      antimycobacterium tuberculosis activity (MIC=0.39-0.78 microg/ml) and the ethyl
      analogue did not show a good activity (MIC>6.25 microg/ml, %inhibition=58). The
      most active compound of the series was n-propyl alpha-[5-(5-nitro-2-thienyl)
      1,3,4-thiadiazole-2-ylthio]acetate (6c) with MIC value of 0.39 microg/ml.

PMID- 14572858
TI  - Synthesis and calcium antagonist activity of 1,4-dihydropyridines containing
      phenylaminoimidazolyl substituents.
AB  - Alkyl ester analogues of nifedipine, in which the ortho-nitrophenyl group at
      position 4 is replaced by 2-methylthio-1-phenylamino-5-imidazolyl substituent,
      were synthesized and evaluated as calcium-channel antagonists using the high K(+)
      contraction of guinea-pig ileal longitudinal smooth muscle. The results for the
      symmetrical esters showed that in the series of alkyl esters increasing the
      length of methylene chain in C-3 and C-5 ester substituents for more than two
      methylene units decreases activity. In the phenylalkyl ester series increasing
      the length of methylene chain also decreases activity. The results demonstrate
      that most of the compounds had similar activity to the reference drug nifedipine.
      In addition, two compounds, 5b and 5f were more active than the nifedipine.

PMID- 14572859
TI  - Pyran derivatives. Part XXI. Antiproliferative and cytotoxic properties of novel
      N-substituted 4-aminocoumarins, their benzo-fused derivatives, and some related 2
      aminochromones.
AB  - The N-substituted tricyclic 2-aminochromone derivatives 1a, 2a, and 2b were
      obtained by treating the corresponding (methylthio) or (methylsulfinyl)
      derivatives 10, 11, or 12, respectively, with an excess of the proper amines.
      Compound 2c was synthesized through the reaction of 2-naphthol with the ethyl N,N
      diphenylmalonamate/POCl(3) reagent 14. The N-substituted 4-aminocoumarin bicyclic
      and tricyclic derivatives 5-8 were prepared by treating the corresponding chloro
      derivatives with the excess suitable amines. Compounds 1, 2, 5-8 were tested in
      vitro for their antiproliferative activity (DNA synthesis inhibition in Ehrlich
      cells) and cytotoxicity (MTT test in HeLa cells). The inhibitory properties of
      three selected compounds (5c, 5e, 7c) on protein and RNA syntheses in Ehrlich
      cells were also evaluated. Among the 27 compounds tested, 10 4-aminocoumarin
      derivatives (5-8) and two 2-aminochromone derivatives (1a and 2a) showed an
      appreciable antiproliferative activity (IC(50) range: 1.74-13.8 microM), whereas
      only four compounds 5-8 exhibited a comparable cytotoxic activity (IC(50) range:
      4.95-12.9 microM).

PMID- 14572860
TI  - In vitro evaluation of food effect on the bioavailability of rifampicin from
      antituberculosis fixed dose combination formulations.
AB  - Rifampicin is one of the major first line anti-tuberculosis drugs used in the
      therapy of tuberculosis. In literature, there are conflicting reports regarding
      effect of food on the bioavailability of rifampicin. In vitro, effect of food on
      the bioavailability can be studied by simulating in vivo conditions in
      dissolution fluid hence, to understand the variable effect of food on rifampicin
      release, dissolution studies were done by simulating in vivo conditions after
      meal intake. In this study, we assessed the effect of hydrodynamic stress in
      presence of food and meal composition on two rifampicin containing fixed dose
      combination formulations by carrying out dissolution at different agitation rates
      (simulation of fasted and fed state) as well as in the presence of different
      percentage of oil (fatty food). Agitation intensity as well as presence of oil
      did not had any influence on rifampicin release from formulation A. This
      formulation had shown excellent release characteristics at all the conditions
      studied. Whereas, formulation B showed agitation rate dependent release and also
      release was affected in presence of oil. Hence, it is concluded that food may not
      have any effect on the release of rifampicin from the formulation and
      subsequently on its bioavailability if the formulation has excellent release
      profile (>85% release in 10 min). Further, effect of food on the rifampicin
      release was a function of dosage form characteristics such as disintegration time
      and dissolution rate, which will subsequently affect the release behavior of a
      formulation in presence of food.

PMID- 14572861
TI  - Substituted 5-aroylpyrazine-2-carboxylic acid derivatives: synthesis and
      biological activity.
AB  - Homolytic aroylation of pyrazine nucleus with various substituted aromatic
      carbaldehydes afforded a series of 5-aroylpyrazine-2-carboxylic acid derivatives.
      The synthetic approach, analytical and spectroscopic data of all compounds
      synthesized, their preliminary in vitro evaluation of antituberculotic and
      antifungal activities, cytotoxicity data and subsequent SAR studies are
      presented. Among all derivatives prepared, only 5-(4-chlorobenzoyl)-pyrazine-2
      carbothioamide (3d) showed promising activity (90% inhibition) against
      Mycobacterium tuberculosis. The highest antifungal effect (MIC<1.95 microM ml(
      1)) against Trichophyton mentagrophytes, the most susceptible fungal strain
      tested, was found for 5-benzoylpyrazine-2-carbothioamide (3a). Thioamides
      exhibited higher in vitro antimicrobial activity than the corresponding amides.

PMID- 14572862
TI  - Proline analogue of melphalan as a prodrug susceptible to the action of prolidase
      in breast cancer MDA-MB 231 cells.
AB  - Proline analogue of melphalan (Mel-pro) was synthesized as a prodrug susceptible
      to the action of ubiquitously distributed, cytosolic imidodipeptidase-prolidase
      [E.C.3.4.13.9]. Conjugation of melphalan (Mel) with proline (Pro) through imido
      bond resulted in formation of a good substrate for prolidase. Cytosolic location
      of prolidase in neoplastic cell suggests that proline analogue of melphalan (Mel
      pro) may serve as a prolidase convertible prodrug. We have compared several
      aspects of pharmacologic actions of Mel and Mel-pro in estrogen-independent
      breast cancer MDA-MB 231 cells. It has been found that Mel-pro is more
      effectively transported into the MDA-MB 231 cells, evokes higher cytotoxicity,
      similar inhibitory effect on DNA synthesis, lower inhibitory effect on collagen
      biosynthesis and reduces IGF-I receptor and MAPkinase expression in MDA-MB 231
      cells, compared to Mel. The results suggest that targeting of prolidase as a Mel
      pro-converting enzyme may serve as a potential strategy in pharmacotherapy of
      breast cancer.

PMID- 14572863
TI  - Synthesis and activity of HCO-Met-Leu-Phe-OMe analogues containing beta-alanine
      or taurine at the central position.
AB  - New synthetic analogues of the chemotactic N-formyltripeptide HCO-Met-Leu-Phe-OMe
      have been synthesized. The reported new models, namely Boc-Met-beta-Ala-Phe-OMe
      (1), HCO-Met-beta-Ala-Phe-OMe (2), Boc-Met-Tau-Phe-OMe (3), HCO-Met-Tau-Phe-OMe
      (4) and HCl.Met-Tau-Phe-OMe (5), are characterized by the presence at the central
      position of a residue of beta-alanine or 2-aminoethanesulfonic acid (taurine)
      replacing the native L-leucine. Whereas tripeptides 1 and 2 have been found quite
      inactive as chemoattractants, all the three models containing the Tau residue
      exhibit a remarkable activity. Superoxide anion production and lysozyme release
      have been also evaluated and the biological results are discussed together with
      the conformational preferences of the examined models.

PMID- 14572864
TI  - Preparation and properties of selected Zn(II)-peptide complexes in suspension.
AB  - The preparation and properties of low soluble, suspended Zn(II) complexes
      containing the selected peptides: tyroliberin (TRH), gonadorelin (GnRH),
      dalarelin and corticothropin (ACTH) were studied. The amount of Zn(II) bound by 1
      muM of the selected peptide (n) was defined, as well as affinity of Zn(II) to the
      peptide (Ka) and the durability of the created complex Zn(II)-peptide (Kd). ACTH
      associated the highest amount of Zn(II), and GnRH the lowest one: 1 microM of
      ACTH complexed 0.81 microM +/- 0.03 Zn(II), the same quantity of GnRH-0.52 microM
      +/- 0.07 and TRH and dalarelin associated 0.75+/-0.03 and 0.79+/-0.02 microM of
      Zn(II), respectively. The closest affinity was stated between Zn(II) and GnRH
      (Ka=157.692+/-21.300 microM(-1)), the smallest-towards ACTH (Ka=1.136+/-0.042
      microM(-1)). The lower amount of Zn(II) associated by the studied peptide, the
      higher was its affinity versus this metal (r=-0.942). The analysis of the
      kinetics of the Zn(II)-peptide linkage revealed that the most stable complexes
      with this metal were formed by GnRH (Kd=0.006+/-0.001 microM(-1)) and by
      dalarelin (Kd=0.020+/-0.001 microM(-1)). Zn(II) with GnRH complexes are about 147
      times more durable than ACTH (Kd=0.880+/-0.033 microM(-1)) ones. It was
      established that the Zn(II)-peptide complexes were more stable in the case of
      lower molecular weight of the peptide (r=0.963), and the inferior number of the
      amino acid residues accessible in the peptide (r=0.967).

PMID- 14572865
TI  - 3-Benzyl-2H-1,3-benzoxazine-2,4(3H)-diones, a new group of antimycobacterial
      compounds against potentially pathogenic strains.
AB  - A series of derivatives of 3-benzyl-2H-benzoxazine-2,4(3H)-dione substituted in
      positions 6, 7 or 8 on the benzoxazine, and in positions 3 or 4 on the benzyl
      moiety was synthesized. The compounds were evaluated for in vitro
      antimycobacterial activity against Mycobacterium avium and two strains of
      Mycobacterium kansasii. The disadvantage of the compounds is in their low
      solubility in water. The antimycobacterial activity of N-benzylsalicylamides
      correlates with that of 3-benzyl-2H-1,3-benzoxazin-2,4(3H)-diones and depends on
      the partition coefficients and electronic indexes.

PMID- 14572866
TI  - Spectophotometric quantitative resolution of hydrochlorothiazide and
      spironolactone in tablets by chemometric analysis methods.
AB  - Spectrophotometric simultaneous determination of hydrochlorothiazide and
      spironolactone in tablets was performed by classical least-squares (CLS), inverse
      least-squares (ILS), principal component regression (PCR) and partial least
      squares (PLS). The methods of the chemometric analysis do not require sample
      pretreatment procedure. A training set of 25 standard mixture containing both
      drugs was prepared in the concentration range of 2-20 mug/ml according to mixture
      design. The multivarate calibrations were obtained by measuring the zero-order
      and first-derivative absorbances at 15 points from 220 to 290 nm using the
      training set. The validation of the multivariate methods was realised by
      analysing the synthetic mixtures of hydrochlorothiazide and spironolactone. The
      result obtained on the synthetic mixture and tablets were statistically compared
      by the one-way ANOVA test. The chemometrics analysis methods were satisfactorily
      applied to the simultaneous determination of hydrochlorothiazide and
      spironolactone in the pharmaceutical tablet formulation.

PMID- 14572867
TI  - A novel sunscreen agent having antimelanoma activity.
AB  - A novel series of eight dibenzoylmethane derivatives having both sunscreen and
      cytotoxic activity has been obtained by derivatizing commercial dibenzoyl
      methanes. Four human cancer cell lines (MCF 7 (breast), NCI ADR (breast
      expressing the multidrug resistance phenotype), NCI 460 (lung) and UACC 62
      (melanoma)) were used for the cytotoxic assay. Eight among the 19
      dibenzoylmethane derivatives showed cytotoxicity against these four cell lines.
      Absorption spectroscopies revealed that these compounds can be used as sunscreens
      against UV radiation.

PMID- 14572868
TI  - Synthesis and structure of novel 2,3, 5,6-tetrahydro-1H-imidazo[2,1
      b][1,3,5]benzotriazepines with vasocontractile activity in rabbit aortic rings.
AB  - A series of novel 2,3,5,6-tetrahydro-1H-imidazo[2,1-b][1,3,5]benzotriazepines (3a
      n) and hydrochlorides (4a-b) were prepared and their structure was determined by
      IR and NMR spectroscopic data as well as by X-ray analysis of the hydrochloride
      4a. The newly synthesized benzotriazepine 4b exhibited concentration-dependent
      vasocontractile activity in isolated rabbit aortic rings. Rimalkalim was found to
      induce a relaxation in rabbit aortic rings precontracted by 4b (3x10(-5) mol).
      Present results indicate that K(ATP)-dependant channels may contribute in the
      contractile activity of benzotriazepine 4b.

PMID- 14572869
TI  - Spectrophotometric determination of propranolol in formulations via oxidative
      coupling with 3-methylbenzothiazoline-2-one hydrazone.
AB  - A simple spectrophotometric method has been developed for the determination of
      propranolol hydrochloride in pure as well as in dosage forms. The method is based
      on the oxidative coupling reaction with 3-methylbenzothiazoline-2-one hydrazone.
      A mixture of an acidic solution of the chromogenic agent and the drug upon
      treatment with ceric ammonium sulfate produces an orange color peaking at 496 nm.
      The absorbance-calibration plot was linear over the range 1-10 microg/ml with
      minimum detectability (S/N=2) of 0.1 microg/ml (3.38x10(-7) M). The molar
      absorbitivity was 3.195x10(3) l/M/cm with correlation coefficient (n=10) of
      0.9999. The different experimental parameters affecting the development and
      stability of the color were carefully studied and optimized. The proposed method
      was applied successfully to the determination of propranolol in its dosage forms.
      A proposal of the reaction pathway was presented.

PMID- 14572870
TI  - Sustained release of bupivacaine from devices based on chitosan.
AB  - Chitosan beads loaded with bupivacaine (16+/-3 microg of drug per milligram of
      beads) were prepared by cross-linking with glutaraldehyde. In vitro drug release
      at pH and temperature conditions similar to those of the biological systems were
      studied. Maximum release of bupivacaine was obtained between 100 and 120 h,
      depending on the presence of lysozyme in the release medium, since the enzyme
      facilitates the release process. A constant release rate of the drug, between 11
      and 15 microg/h, was observed for 30 h. In order to prolong bupivacaine release,
      the drug-loaded chitosan beads were coated with a poly(DL-lactide-co-glycolide)
      film. The resulting device allows the drug to be released in a sustained form; a
      constant release rate between 28.5 and 29.5 microg/h was obtained for 3 days, and
      the maximum release of bupivacaine took place at day 9. The in vitro results
      indicate a possible application of these bupivacaine loaded chitosan systems as
      drug release devices with an analgesic action. Thus, they could be used in the
      treatment of dental pain in the buccal cavity, where drug release would be made
      easier by lysozyme of the saliva.

PMID- 14572871
TI  - Synthesis and antagonistic activity of four new 2-alkyl-N-biphenyl fused
      imidazoles on angiotensin II receptors.
AB  - In the current study, four new 2-alkyl-N-biphenyl fused imidazoles were
      synthesized and the pharmacological properties of these compounds as angiotensin
      II antagonists were studied. First, the potency of the synthesized compounds on
      guinea-pig ileum was evaluated and the vasopressor effect of the most potent
      compound 6a was compared with losartan on isolated perfused rat kidney. The
      antagonistic activity of compound 6a (sodium 2-propyl-5-carbomethoxy-1-[(biphenyl
      4-yl)methyl]pyrrolo[3,2-d]imidazole-2'-carboxylate) on angiotensin II receptors
      was greater than the other synthesized compounds and in isolated perfused rat
      kidney was similar to losartan.

PMID- 14572872
TI  - Synthesis and relative binding affinity to human steroid receptors of substituted
      3-aryloxycoumarins.
AB  - The synthesis of a set of substituted 3-aryloxycoumarins was performed. The study
      of the relations between their structure and their relative binding affinity to
      human androgen, progesterone, alpha and beta estrogen receptors was achieved.

PMID- 14572873
TI  - Plasmon-waveguide resonance spectroscopy: a new tool for investigating signal
      transduction by G-protein coupled receptors.
AB  - Plasmon-waveguide resonance (PWR) spectroscopy provides a highly sensitive method
      for characterizing the kinetics, affinities and conformational changes involved
      in ligand binding to G-protein coupled receptors, without the need for
      radioactive or other labeling strategies. In the case of the cloned delta-opioid
      receptor from human brain incorporated into a lipid bilayer, we have shown that
      affinities determined in this way are consistent with those measured by standard
      binding procedures using membranes or whole cells containing the receptors, and
      that the spectral and kinetic properties of the binding processes allow facile
      distinction between agonist, inverse agonist, and antagonist ligands. We have
      also shown by direct measurements that G-protein binding affinities and the
      ability to undergo GTP/GDP exchange are dependent upon the type of ligand pre
      bound to the receptor. PWR spectroscopy thus provides a powerful new approach to
      investigating signal transduction in biological membrane systems.

PMID- 14572874
TI  - Vitamin D receptor gene polymorphism is associated with chronic periodontitis.
AB  - Chronic periodontitis (CP) is caused by enhanced resorption of the alveolar bone
      supporting the teeth and is associated with intraoral inflammation after
      infection with certain bacteria. The VDR gene polymorphism was reported recently
      to be deeply related to the occurrence of tuberculosis and infection of chronic
      hepatitis B virus. This may be interpreted to indicate a close relationship
      between VDR gene polymorphism and the immunological action, because vitamin D
      activates monocytes, stimulates cell-mediated immunity, and suppresses lymphocyte
      proliferation. The purpose of the present study was to clarify whether
      polymorphisms in VDR gene exons are associated with the incidence of CP. A case
      controlled study was performed on a group of 168 unrelated Japanese subjects
      whose ages ranged from 35 to 65 years. The Taq I polymorphism in the VDR gene was
      found to be associated significantly with CP (X2=4.48, P=0.034). We performed
      multiple logistic regression analyses on the TT genotype, which was found to be
      associated with CP, and on well-recognized risk factors, smoking and diabetes.
      The odds ratio (OR) for the genotype (TT/Tt) was 2.73 (95% CI 1.11-6.68,
      P=0.028), being larger than the unadjusted value. This indicates that the VDR
      gene polymorphism (TT genotype) is a risk factor for CP, independently of smoking
      and diabetes.

PMID- 14572875
TI  - Antihyperalgesic effect of simultaneously released hydromorphone and bupivacaine
      from polymer fibers in the rat chronic constriction injury model.
AB  - We aimed to evaluate the antihyperalgesic efficacy of a combination of
      hydromorphone (HM) and bupivacaine (BP) delivered via controlled release from a
      biodegradable cylindrical rod. In vivo studies were performed using a rat model
      of thermal hyperalgesia induced by chronic constriction injury (CCI) of the
      sciatic nerve with loose ligatures. Poly(lactic-co-glycolic acid) (PLGA) rods (10
      mm length, 1 mm diameter) loaded with HM (5 mg per rod), BP (5 mg per rod) or no
      drug (placebo) were implanted subcutaneously, in single or dual pairs, adjacent
      to the constriction injury, immediately after nerve ligation. We evaluated the
      efficacy of two dose levels for each drug, alone or in combination, in
      attenuating thermal hyperesthesia over a period of 12 days according to a
      prevention protocol. Plasma levels of drugs released from the rods and also
      released in an in vitro simulation were evaluated. In vitro studies demonstrated
      that drug release is maintained for at least 10 days. HM (5 mg) alone and BP (5
      mg) alone did not attenuate hyperalgesia. Their combination provided a
      significant increase in the paw withdrawal latency as compared to single agents
      or placebo. When the dose in each group was doubled, implanting four rods,
      significant attenuation of hyperalgesia was observed. Analyses of rods retrieved
      after termination of experiments (after 12 days) revealed 30% residual HM and 70%
      residual BP content. Prolonged delivery of HM and BP alone or in combination via
      locally applied PLGA rods may offer a feasible alternative to provide long
      lasting analgesia.

PMID- 14572876
TI  - Reproducibility of the circadian rhythms of serum cortisol and melatonin in
      healthy subjects: a study of three different 24-h cycles over six weeks.
AB  - Plasma melatonin and cortisol are characterized by a marked circadian rhythm, but
      little information is available about the reproducibility and stability of these
      rhythms over several weeks in the same subjects. This study examined the
      characteristics of these rhythms in 31 healthy human subjects 20 to 30 years of
      age. They were synchronized with a diurnal activity from 0800 to 2300 and
      nocturnal rest. They participated in three 24-hour sessions (S1, S2, and S3): S2
      took place two weeks after S1 and S3 4 weeks after S2. Blood samples were taken
      during each session at 3-hour intervals from 1100 to 2000 and hourly from 2200 to
      0800. Comparison of the circadian rhythms between groups used repeated measures 2
      way ANOVA, the cosinor method, and Bingham's test. Intraindividual variations
      were compared by the cosinor method and Bingham's test. The groups did not
      differ, but a slight difference in the amplitude or acrophase of individual
      circadian rhythms was observed in 5 of 31 subjects for melatonin and 1 of 31 for
      cortisol. The circadian means did not differ over the three sessions. These
      results show that the circadian profile of cortisol and melatonin are highly
      reproducible over a six-week period, in both individuals and groups. Our study
      clearly shows that these hormones can be considered to be stable markers of the
      circadian time structure and therefore useful tools to validate rhythms'
      synchronisation of human subjects.

PMID- 14572877
TI  - Effects of ethanol on deep pain evoked by formalin injected in TMJ of rat.
AB  - It has been reported that ethanol can alter nociceptive sensitivity from
      superficial tissues, such as skin and subcutaneous region. However, the influence
      of ethanol on deep pain conditions is not understood. The aim of this study was
      to demonstrate the acute, chronic and ethanol withdrawal effects on nociceptive
      behavioral responses induced by the injection of formalin into the
      temporomandibular joint (TMJ) region of rats. In experiment 1, rats were injected
      with ethanol (2,5 g/Kg, i.p.) or an equal volume of saline 15 min before the
      administration of formalin (1.5%) into the TMJ. Rats pretreated with ethanol
      showed a decrease in nociceptive behavioral responses. In experiment 2, rats were
      given an ethanol solution (6.5%) or tap water to drink for 4 and 10 days. On day
      4, the animals (ethanol group) showed amounts of analgesia when submitted to the
      TMJ formalin test. Tolerance to the antinociceptive effects was observed on day
      10. Behavioral hyperalgesia was verified 12 hr after withdrawal in another group
      that drank ethanol for 10 days. These results show that ethanol can affect the
      nociceptive responses related to deep pain evoked by the TMJ formalin test.

PMID- 14572878
TI  - Lentin, a novel and potent antifungal protein from shitake mushroom with
      inhibitory effects on activity of human immunodeficiency virus-1 reverse
      transcriptase and proliferation of leukemia cells.
AB  - From the fruiting bodies of the edible mushroom Lentinus edodes, a novel protein
      designated lentin with potent antifungal activity was isolated. Lentin was
      unadsorbed on DEAE-cellulose, and adsorbed on Affi-gel blue gel and Mono S. The N
      terminal sequence of lentin manifested similarity to endoglucanase. Lentin, which
      had a molecular mass of 27.5 kDa, inhibited mycelial growth in a variety of
      fungal species including Physalospora piricola, Botrytis cinerea and
      Mycosphaerella arachidicola. Lentin also exerted an inhibitory activity on HIV-1
      reverse transcriptase and proliferation of leukemia cells.

PMID- 14572879
TI  - GH responses to GHRH and GHRP-6 in Streptozotocin (STZ)-diabetic rats.
AB  - GH responses to GHRH, the physiologic hypothalamic stimulus, and GHRP-6, a
      synthetic hexapeptide that binds the Ghrelin receptor, were studied in rats
      treated with streptozotocin (STZ), an experimental model of diabetes. Sprague
      Dawley male rats received a single injection either of STZ (70 mg/Kg in 0.01 M
      SSC, i.p.) or of the vehicle (0.01 M SSC). GH responses were challenged with two
      different doses of GHRH (1 and 10 microg/kg) or GHRP-6 (3 and 30 microg/kg) and
      with a combination of both at low (1 + 3 microg/kg) or high (10 + 30 microg/kg)
      doses, respectively. We observed a dose-dependent effect for GH responses to GHRH
      both in STZ-treated rats and in controls. However, we could not find significant
      differences between STZ-rats and controls. GH responses to GHRP-6 occurred in a
      dose-dependent manner in STZ-rats, but not in controls. GH responses to GHRP-6 in
      both groups were clearly lower than those elicited by GHRH. GH responses to 30
      microg/Kg of GHRP-6 were significantly greater in STZ-rats than in controls (AUC:
      3549.9 +/- 1001.4 vs. 2046.4 +/- 711.7; p<0.05). The combined administration of
      GHRH plus GHRP-6 was the most potent stimuli for GH in both groups. The
      administration of doses in the lower range (1 + 3 microg/Kg, GHRH + GHRP-6
      respectively) induced a great peak of GH in STZ-rats and in control rats,
      revealing a synergistic effect of GHRH and GHRP-6 in both groups. When the higher
      doses were administered (10 + 30 microg/kg), GH levels in time 5, and AUC were
      significantly higher in control rats. In addition, a negative correlation between
      WT (weight tendency) values and GH responses, represented as AUC, could be
      established in STZ-rats (r2=-0.566, p=0.004 for GHRH; r2=-0.412, p=0.028 for GHRP
      6). Thus, the more negative the values of WT were, the more severe the metabolic
      alteration and, therefore, the higher the GH response to GHRH and GHRHP-6. In
      conclusion, our results do not support the existence of a functional hypothalamic
      hypertone of SS in diabetic rats, as GH responses were not usually reduced in STZ
      rats, except when both secretagogues were administered together at the higher
      doses. Besides, GH responses to GHRH and GHRP-6 were inversely correlated with
      the severity of the metabolic alteration in STZ-rats, meaning that worse
      glycaemic control promoted higher GH secretion. These results resemble those
      found in humans, where GH responses to secretagogues are increased in type-1
      diabetes and depend on hyperglycaemia, and are representative of not well
      controlled insulin-dependent diabetic status.

PMID- 14572880
TI  - Effects of aging and cyclosporin treatment on the hepatobiliary efflux of
      glutathione.
AB  - The aim of this study was to investigate the effects of cyclosporin (CyA)
      treatment on biliary glutathione efflux in rats of different ages (1, 2, 4, and
      24 months). CyA treatment reduced the liver content of total glutathione in 1-, 2
      and 24 month old rats (-30%, -43% and -30%, respectively). By contrast, oxidized
      glutathione (GSSG) concentration in liver tended to increase, although non
      significantly, in the rats aged 4 and 24 month (+36% and +28%, respectively). The
      oxidized-to-reduced glutathione ratio was significantly increased in 2-, 4- and
      24 month old animals (+23%, +36% and >100%, respectively). Regarding biliary
      glutathione, our data indicate that efflux rates of total glutathione in control
      (untreated) rats increased to a maximum at 4 months, and decreased (-56%) in 24
      month old rats, although values were still higher than those from young animals.
      CyA treatment significantly reduced biliary glutathione secretion except in 24
      month old rats (-98%, -66% and -32%, at 1, 2 and 4 month, respectively). In
      addition, following inhibition of the intrabiliary catabolism of the tripeptide
      by acivicin, glutathione efflux rates into bile were significantly reduced by the
      drug only in 1- and 2 month old rats (-29% and -55%, respectively) and even
      tended to increase, although non significantly, in oldest animals. Our data
      indicate that inhibition of biliary glutathione efflux by CyA was greater in
      younger rats and support the view that increased intrabiliary catabolism of the
      tripeptide and inhibition of its canalicular transport could contribute to the
      decline in biliary glutathione secretion induced by the drug.

PMID- 14572881
TI  - Versican G3 domain enhances cellular adhesion and proliferation of bovine
      intervertebral disc cells cultured in vitro.
AB  - The functional role of versican in influencing intervertebral disc cell adhesion
      and proliferation was analyzed in bovine intervertebral disc. We have previously
      demonstrated the C-terminal globular G3 (or selectin-like) domain of versican to
      influence mesenchymal chondrogenesis and fibroblast proliferation in vitro. For
      this study, a versican G3 expression construct was generated to examine the role
      of the G3 domain of versican. Nucleus pulposus and annulus fibrosus cells were
      isolated from adult bovine caudal discs using sequential enzymatic digestion and
      versican expression characterized by RT-PCR. In cell proliferation assays, we
      observed that there was greater cellular proliferation in the presence of
      versican G3 for both disc cell types. The higher proliferation rate of annulus
      fibrosus cells when compared to nucleus pulposus cells seeded in monolayer
      supports heterogeneity of intervertebral disc cell populations. The presence of
      versican G3 construct enhanced the adhesion of isolated nucleus pulposus and
      annulus fibrosus cells approximately 4 to 6 fold, respectively. Cellular adhesion
      was greater in the presence of versican G3 in a dose dependent manner. G3 product
      was purified using affinity columns, and the purified G3 also enhanced cell
      adhesion.

PMID- 14572882
TI  - Impaired nitric oxide synthase-dependent dilatation of cerebral arterioles in
      type II diabetic rats.
AB  - The goals of this study were to determine the effects of type II diabetes
      mellitus on nitric oxide synthase-dependent responses of cerebral arterioles and
      on endothelial nitric oxide synthase (eNOS) protein in cerebral arterioles. We
      examined dilatation of cerebral (pial) arterioles in 13-15 week old male lean and
      diabetic obese Zucker rats in response to nitric oxide synthase-dependent
      agonists (acetylcholine and adenosine diphosphate (ADP)) and a nitric oxide
      synthase-independent agonist (nitroglycerin). We found that acetylcholine (10
      microM) increased cerebral arteriolar diameter by 10 +/- 3% (mean +/- SE) in lean
      Zucker rats, but by only 2 +/- 2% in diabetic obese Zucker rats (p<0.05). In
      addition, ADP (100 microM) increased cerebral arteriolar diameter by 20 +/- 2% in
      lean Zucker rats, but by only 8 +/- 2% in diabetic obese Zucker rats (p<0.05). In
      contrast, nitroglycerin produced similar vasodilatation in lean and diabetic
      obese Zucker rats. Thus, impaired dilatation of cerebral arterioles in diabetic
      obese Zucker rats is not related to non-specific impairment of vasodilatation.
      Following these functional studies, we harvested cerebral microvessels for
      Western blot analysis of eNOS protein. We found that eNOS protein was
      significantly higher in diabetic obese Zucker rats than in lean Zucker rats
      (p<0.05). Thus, type II diabetes mellitus impairs nitric oxide synthase-dependent
      responses of cerebral arterioles. In addition, eNOS protein from cerebral blood
      vessels is increased in diabetic obese Zucker rats.

PMID- 14572883
TI  - [6]-Gingerol inhibits nitric oxide synthesis in activated J774.1 mouse
      macrophages and prevents peroxynitrite-induced oxidation and nitration reactions.
AB  - Reactive nitrogen species (RNS), such as nitric oxide (NO) and its derivatives,
      e.g. peroxynitrite (ONOO-), have been proposed as being able to influence signal
      transduction and cause DNA damage, contributing to carcinogenic processes. In
      this study, the effect of [6]-gingerol, a pungent phenolic compound present in
      ginger (Zingiber officinale Roscoe), on NO synthesis in lipopolysaccharide (LPS)
      activated J774.1 macrophages was tested, and the protective ability of this
      compound against peroxynitrite-mediated oxidation and nitration reactions were
      evaluated. [6]-Gingerol exhibited dose-dependent inhibition of NO production and
      significant reduction of inducible NO synthase (iNOS) in LPS-stimulated J774.1
      cells. Moreover, [6]-gingerol effectively suppressed peroxynitrite-induced
      oxidation of dichlorodihydrofluorescein, oxidative single strand breaks in
      supercoiled pTZ 18U plasmid DNA, and formation of 3-nitrotyrosine in bovine serum
      albumin (BSA) and J774.1 cells. Our results indicate that [6]-gingerol is a
      potent inhibitor of NO synthesis and also an effective protector against
      peroxynitrite-mediated damage.

PMID- 14572884
TI  - Why we should "just say no" to exclusive "abstinence-only" funding.

PMID- 14572885
TI  - Hormonal contraception during lactation. systematic review of randomized
      controlled trials.
AB  - Contraception choices may be limited for lactating women due to concerns about
      hormonal effects on quality and quantity of milk, passage of hormones to the
      infant and infant growth. We conducted a systematic review of randomized
      controlled trials to determine the effect of hormonal contraception on lactation.
      We sought all randomized controlled trials, reported in any language, that
      included any form of hormonal contraception compared with another form of
      hormonal contraception, nonhormonal contraception or placebo during lactation.
      Seven reports from five randomized controlled trials met the inclusion criteria.
      Most of the five trials did not specify their method used to generate a random
      sequence, method of allocation concealment, blinding of treatments or use of an
      intention-to-treat analysis. Additionally, high loss-to-follow-up rates
      invalidated at least two trials. The findings from two trials comparing oral
      contraceptives to placebo during lactation were conflicting. Another trial found
      no inhibitory effects on lactation from progestin-only contraceptives. Finally,
      the World Health Organization trial found a statistically significant decline in
      breast milk volume in women using combined oral contraceptives compared to women
      using progestin-only pills. However, infant growth for the two groups did not
      differ. The limited evidence from randomized controlled trials on the effect of
      hormonal contraceptives during lactation is of poor quality and insufficient to
      establish an effect of hormonal contraception, if any, on milk quality and
      quantity. At least one properly conducted randomized controlled trial of adequate
      size is urgently needed to make recommendations regarding hormonal contraceptive
      use for lactating women.

PMID- 14572886
TI  - Effects of a phasic oral contraceptive containing desogestrel on facial seborrhea
      and acne.
AB  - BACKGROUND: The combined oral contraceptive containing ethinylestradiol and the
      selective progestogen, desogestrel, in a phasic regimen (DSG-OC, Tri-merci) has
      been shown to reduce facial oiliness. OBJECTIVE: This study was designed to
      evaluate further the effects of this OC on the skin of women with facial
      seborrhea and mild or moderate acne. DESIGN AND METHODS: This was an open,
      noncomparative, bicenter study in 60 healthy Russian women, aged 18-30 years,
      with facial seborrhea and mild or moderate facial acne, who wished to use oral
      contraception. All women received the OC containing desogestrel (50/100/150
      microg) and ethinylestradiol (35/30/30 microg) for three phases of 7 days
      followed by a 7-day pill-free interval, for six cycles. Seborrhea was assessed
      using the Sebutape technique, in which strips of adhesive microporous polymeric
      film pressed onto facial sites are used to assess sebaceous activity. Acne was
      assessed by counting facial lesions. Subjective evaluations of skin and hair
      condition, patients' feelings to them and satisfaction with the OC were made
      using a visual analogue scale (VAS). Assessments were made at baseline, and after
      one, three and six treatment cycles. RESULTS: Sebutape assessments of seborrhea
      were significantly improved, on the right and left cheeks, after one treatment
      cycle, and on the forehead after three treatment cycles. These improvements
      increased steadily and were much larger at the end of Cycle 6. Acne grades were
      significantly improved after three and six treatment cycles. VAS scores in
      response to questions dealing with self-esteem and self-confidence were
      significantly improved after three cycles and in some cases after just one cycle.
      The women's views of their skin and hair (greasiness) were correspondingly
      significantly improved. Subjective assessments indicated that after one, three
      and six cycles, 69%, 93% and 98%, respectively, of women were satisfied or very
      satisfied with the DSG-OC. CONCLUSION: In women with facial seborrhea and mild or
      moderate acne, the use of DSG-OC appears to improve seborrhea after just one
      cycle and acne grades after three cycles. These improvements are accompanied by
      increases in self-esteem and confidence.

PMID- 14572887
TI  - Medical abortion. defining success and categorizing failures.
AB  - Medical abortion was performed in 461 consecutive women with gestational age </=
      63 days using a regimen of mifepristone 600 mg followed 2 days later by gemeprost
      1 mg vaginally. Success, defined as no surgical intervention, declined from 98.7%
      after 2 weeks to 94.6% after 15 weeks. The difference in short- and long-term
      success rates increased with increasing gestational age. The majority of failures
      (76%) were diagnosed more than 2 weeks after initiation of the abortion. At a 2
      week follow-up visit, the women who turned out to be failures had a larger
      endometrial width, higher beta-hCG values and smaller reductions of beta-hCG than
      those treated successfully. To optimize comparison of success rates after
      different medical abortion regimens, we suggest that the criteria for success are
      stated clearly, that the success rates are stratified according to gestational
      age and that the indications for secondary intervention are categorized.

PMID- 14572888
TI  - Providing emergency contraceptive pills "behind-the-counter": opinions among
      Minnesota healthcare providers.
AB  - We assessed strategies to increase access to emergency contraceptive pills (ECPs)
      among healthcare providers in Minnesota. We hypothesized that physicians, mid
      level practitioners (nurse practitioners, certified nurse midwives and physician
      assistants) and pharmacists would support collaborative drug therapy agreements
      to enable pharmacist provision of ECPs without a prescription ("behind-the
      counter"). We assessed these and other strategies to improve access to ECPs among
      a random sample of 1000 healthcare providers using mailed surveys. Obtaining a
      50% response rate (n = 495), we discovered that the majority of total respondents
      (and a significant proportion of physicians) favored improving ECP availability
      "behind-the-counter", over-the-counter or both. Support among mid-level
      practitioners was more guarded: 39% of respondents supported pharmacist provision
      of ECPs and more than 20% wanted more information. Among pharmacists, 46% said
      they would participate in a collaborative protocol for provision of ECPs. Results
      demonstrate the degree of support and illuminate potential obstacles to
      pharmacist-provided ECPs. While there is general support among Minnesota
      providers regarding ECPs, a campaign to educate providers about recent scientific
      data on ECPs and collaborative drug therapy agreements should be initiated.

PMID- 14572889
TI  - Pharmacists' knowledge and the difficulty of obtaining emergency contraception.
AB  - This cross-sectional study was performed to examine knowledge and attitudes among
      pharmacists about emergency contraception (EC) and determine the factors
      associated with their provision of EC. A random systematic sampling method was
      used to obtain a sample (N = 320) of pharmacies in Pennsylvania. A "mystery
      shopper" telephone survey method was utilized. Only 35% of pharmacists stated
      that they would be able to fill a prescription for EC that day. Also, many
      community pharmacists do not have sufficient or accurate information about EC. In
      a logistic regression model, pharmacists' lack of information relates to the low
      proportion of pharmacists able to dispense it. In conclusion, access to EC from
      community pharmacists in Pennsylvania is severely limited. Interventions to
      improve timely access to EC involve increased education for pharmacists, as well
      as increased community request for these products as an incentive for pharmacists
      to stock them.

PMID- 14572890
TI  - A study of the efficacy of cervical ripening with nitric oxide donor versus
      placebo for cervical priming before second-trimester termination of pregnancy.
AB  - This was a double-blind randomized control study to evaluate the efficacy of
      cervical priming by nitric oxide donor before second-trimester induced abortion.
      One-hundred healthy women with a singleton pregnancy between 14 and 20 weeks of
      gestation were randomized into either 40 mg isosorbide mononitrate or placebo,
      given intravaginally 12 h before induction. This was followed by intravaginal
      misoprostol induction. The induction-abortion interval, abortion rate, side
      effects and the woman's acceptability of the priming agent were recorded. All
      women completed the study and there was no severe complication recorded. There
      was no significant difference in the induction-abortion interval and abortion
      rate between the two groups. Isosorbide mononitrate group reported significantly
      more side effects of headache. More than 90% of the women in both groups found
      the priming agent acceptable. The application of intravaginal nitric oxide donors
      prior to the prostaglandins induction did not significantly improve the second
      trimester induced-abortion process.

PMID- 14572891
TI  - Disruption of the upper female reproductive tract epithelium by nonoxynol-9.
AB  - Spermicides containing nonoxynol-9 (N-9) may increase HIV transmission. In women,
      intravaginal N-9 is found in the uterus shortly after its insertion. Exposure of
      the female upper reproductive tract to N-9 may alter epithelial integrity,
      thereby increasing HIV transmission risk. Our goal was to characterize the
      histological effects of N-9 on uterine epithelium in an animal model. Female mice
      were exposed to intravaginal or intrauterine Advantage-S (N-9), Replens, K-Y(R)
      jelly or water. After various exposure times, mice were sacrificed and stained
      uterine tissue sections were analyzed by a pathologist blinded to
      treatment.Intravaginal and intrauterine N-9 administration resulted in disruption
      of uterine epithelium compared to Replens, K-Y jelly or water. N-9 caused rapid
      (within 10 min), focal, uterine epithelial sloughing and complete epithelial loss
      within 24 h. Epithelial regeneration began 48 h after exposure N-9 and was
      completely restored within 72 h; the new epithelial layer, however, was composed
      of cuboidal cells instead of normally present columnar cells. In addition,
      hemorrhage and necrosis were present are all time points examined. Our results
      demonstrate for the first time that N-9 has a deleterious effect on uterine
      epithelium. Although these results were observed in a mouse model, similar
      disruption of the upper reproductive tract epithelium in women by N-9 may
      facilitate HIV infection and serve as an unrecognized portal of human HIV
      transmission.

PMID- 14572892
TI  - Cross-border procurement of contraception. estimates from a postpartum survey in
      El Paso, Texas.
AB  - Along the US-Mexico border, US residents have the option of crossing to Mexico in
      order to purchase hormonal contraception sold over-the-counter at very low prices
      in pharmacies. We investigated the prevalence of cross-border contraceptive
      procurement by way of a survey of 3134 women who delivered in a large public
      hospital in El Paso, Texas, between 1996 and 1997. Pills, injectables, condoms
      and IUDs were the most commonly used methods by women in the birth interval
      preceding delivery. Among multiparous women, 41% of pills and 54% of injectables
      were obtained in Mexico. However, almost all condoms were obtained in the United
      States. In this largely Hispanic population, the prevalence of cross-border
      procurement was highest among women who were born and educated in Mexico.
      Discontinuation of pills and injectables was lower when obtained across the
      border than in the United States. These findings support the proposition that
      reducing the medical requirements to acquire pills and injectables and making
      them available at low cost would augment their use in low-income populations.

PMID- 14572893
TI  - Synergistic effects of DL111-IT in combination with mifepristone and misoprostol
      on termination of early pregnancy in preclinical studies.
AB  - This study evaluated the effectiveness and acute toxicity of DL111-IT combined
      with mifepristone (RU486) and misoprostol (MISO) on early pregnancy termination.
      In the pregnant rats experiments, the ED(50) values of RU486 in two-drug
      combinations were 0.16 (combined with DL111-IT) and 0.40 (combined with MISO) mg
      x kg(-1) x d(-1), while in three-drug combination treatment group (DL111-IT 9.0
      mg x kg(-1) (<ED(5)) + MISO 0.30 mg x kg(-1) + RU486 0.012-0.5 mg x kg(-1) x d(
      1)), the ED(50) of RU486 was decreased to 0.07 (0.04-0.10) mg x kg(-1) x d(-1).
      In guinea pigs, significant enhancement of early pregnancy termination was only
      observed in three-drug combination treatment with MISO 0.10 mg x kg(-1) + RU486
      0.05 mg x kg(-1) (<minimum effective doses) + high dosages of DL111-IT (0.05-0.10
      mg x kg(-1)). DL111-IT induced pregnant rat uterine contraction in vitro, and the
      contractive efficacy was 60% of that induced by MISO. Multiple intramuscular
      injections of DL111-IT in vivo could significantly enhance the MISO-stimulated
      uterine contractions of pregnant rats in vitro. DL111-IT 600 mg x kg(-1) or RU486
      1000 mg x kg(-1) induced pigeon vomiting, with latent periods of 32.3 +/- 12.0
      min and 50.4 +/- 16.0 min, respectively. In three-drug combination group, the
      latent period of vomiting was significantly extended to 86.3 +/- 36.2 min. MISO
      also significantly decreased the frequency of vomiting within 4 h after
      administration of DL111-IT and RU486. In the experiment of mice acute toxicity,
      the LD(50) values and 95% confidence limit of DL111-IT (i.p.) alone and in
      combination with RU486 and MISO were 1379.4 (1278.2-1514.7) mg x kg(-1) and
      1574.1 (1407.8-1762.7) mg x kg(-1), respectively. There was no significant
      difference. All data suggested that DL111-IT in combination with RU486 and MISO
      significantly increased the effect on early pregnancy termination without
      increasing acute toxicity compared to the treatment of DL111-IT alone, and this
      combination may be a promising regimen for early pregnancy termination.

PMID- 14572894
TI  - Bcl-2 and Bax are involved in experimental cryptorchidism-induced testicular germ
      cell apoptosis in rhesus monkey.
AB  - Apoptosis occurs spontaneously during spermatogenesis. However, little is known
      about its regulation in primate. Using an experimental cryptorchidism model in
      rhesus monkey, we have investigated the relationship between apoptosis and the
      Bcl-2 family members, Bcl-2 and Bax. Apoptotic cells were identified by in situ
      end labeling of fragmented DNA. The expressions of Bcl-2 and Bax in the testes
      during the heat stress-induced testicular germ cell apoptosis were detected by
      immunohistochemistry and Western blot techniques. The results showed that the
      apoptotic signals increased after heat treatment and the most susceptible cell
      types were spermatocytes and spermatids. A redistribution of Bax from the
      cytoplasmic to nuclear localization in some germ cells was observed. However, its
      total expression levels in the cells remained unchanged in the cryptorchid testes
      as determined by Western blot analysis; on the other hand, Bcl-2 levels increased
      significantly in response to heat stress. The subcellular redistribution of Bax
      and the increase in Bcl-2 expression in the cryptorchid testis suggest an
      involvement of Bcl-2 family members in heat stress-induced germ-cell apoptosis.

PMID- 14572895
TI  - Pregnancy interceptive activity of Melia azedarach Linn. in adult female Sprague
      Dawley rats.
AB  - Ethanolic extract of the root of Melia azedarach Linn. (family: Meliaceae)
      collected from the Institute campus intercepted pregnancy in 60% and 75% adult
      female rats when administered at 250 and 500 mg/kg daily doses, respectively, on
      Days 1-10 post-coitum by the oral route. On fractionation, the activity was
      localized in the chloroform fraction of the ethanolic extract, which showed 80
      100% activity at 250 mg/kg daily dose in repeat tests. In animals that became
      pregnant, there was also a significant reduction in mean number of implantations
      and all the implantations exhibited signs of resorption. Of the four major
      compounds isolated in sufficient quantity and characterized from the active
      chloroform fraction, two compounds showed only marginal (50%) contragestational
      effect. Further exploration of the active chloroform fraction, which is also
      devoid of estrogen agonistic activity at the contraceptive dose in immature rat
      bioassay, is being undertaken to identify and characterize the active
      principle(s).

PMID- 14572896
TI  - Group V and X secretory phospholipase A(2)s-induced modification of high-density
      lipoprotein linked to the reduction of its antiatherogenic functions.
AB  - The quantitative or qualitative decline of high-density lipoprotein (HDL) is
      linked to the pathogenesis of atherosclerosis because of its antiatherogenic
      functions, including the mediation of reverse cholesterol transport from the
      peripheral cells to the liver. We have recently shown that group X secretory
      phospholipase A(2) (sPLA(2)-X) is involved in the pathogenesis of atherosclerosis
      via potent lipolysis of low-density lipoprotein (LDL) leading to macrophage foam
      cell formation. We demonstrate here that sPLA(2)-X as well as group V secretory
      PLA(2) (sPLA(2)-V), another group of sPLA(2) that can potently hydrolyze
      phosphatidylcholine (PC), also possess potent hydrolytic potency for PC in HDL
      linked to the production of a large amount of unsaturated fatty acids and
      lysophosphatidylcholine (lysoPC). In contrast, the classical types of group IB
      and IIA secretory PLA(2)s evoked little, if any, lypolytic modification of HDL.
      Treatment with sPLA(2)-X or -V also caused an increase in the negative charge of
      HDL with no oxidation and little modification of apolipoprotein AI (apoAI).
      Modification with sPLA(2)-X or -V resulted in significant decrease in the
      capacity of HDL to cause cellular cholesterol efflux from lipid-loaded
      macrophages. Immunohistochemical analysis revealed significant expression of
      sPLA(2)-X in foam cell lesions in the arterial intima of Watanabe heritable
      hyperlipidemic (WHHL) rabbit. These findings suggest that lipolytic modification
      of HDL by sPLA(2)-X or -V causes drastic change of HDL in terms of the production
      of a large amount of unsaturated fatty acids and lysoPC linked to the reduction
      of its antiatherogenic functions. These sPLA(2)-mediated modifications of plasma
      lipoproteins might be relevant to the pathogenesis of atherosclerosis.

PMID- 14572897
TI  - Identification of Taxreb107 as a lactogenic hormone responsive gene in mammary
      epithelial cells.
AB  - Mammary gland development and differentiation is regulated by a number of growth
      factors and hormones. Milk protein gene expression represents a hallmark of
      functional mammary epithelial differentiation and is coordinated by the
      lactogenic hormone prolactin and glucocorticoids. To date, few 'early-response'
      genes transcriptionally activated by lactogenic hormones have been described. We
      have used representational difference analysis (RDA) to search for lactogenic
      responsive genes in SCp2 mouse mammary epithelial cells. One of the cDNAs
      identified encoded the DNA-binding protein Taxreb107, originally identified as a
      HTLV-I Tax responsive element binding protein. Increased Taxreb107 expression was
      confirmed following prolactin and dexamethasone-induced differentiation of SCp2
      and HC11 mammary epithelial cells. Taxreb107 RNA levels were developmentally
      regulated in the mouse mammary gland, where levels increased substantially during
      mid- and late pregnancy and persisted during lactation. Overexpression of an
      antisense Taxreb107 cDNA construct or antisense oligonucleotide in HC11 mammary
      epithelial cells attenuated milk protein gene expression following prolactin and
      dexamethasone treatment. These findings indicate a role for Taxreb107 as a
      lactogenic hormone-responsive gene during differentiation of the mammary gland.

PMID- 14572898
TI  - Overexpression of catalase or Bcl-2 delays or prevents alterations in
      phospholipid metabolism during glucocorticoid-induced apoptosis in WEHI7.2 cells.
AB  - Dexamethasone-treated WEHI7.2 mouse thymoma cells readily undergo apoptosis.
      WEHI7.2 variants that overexpress catalase (CAT38) or Bcl-2 (Hb12) show a delay
      or lack of apoptosis, respectively, when treated with dexamethasone. This is
      accompanied by a delay or lack of cytochrome c release from the mitochondria
      suggesting that alterations in the signaling phase of apoptosis are responsible
      for the observed resistance. Because membranes are a rich source of signaling
      molecules, we have used 31P NMR spectroscopy to compare phospholipids and their
      metabolites in WEHI7.2, CAT38 and Hb12 cells after dexamethasone treatment.
      Increased lysophosphatidylcholine (lysoPtdC) content accompanied
      phosphatidylserine (PtdS) externalization in the WEHI7.2 cells. Both changes were
      delayed in CAT38 cells suggesting phosphatidylcholine (PtdC) metabolites may play
      a role in steroid-induced apoptotic signaling. The steroid-resistant Hb12 cells
      showed a dramatic increase in glycerophosphocholine (GPC) content, suggesting
      increased phospholipid turnover may contribute to the anti-apoptotic mechanism of
      Bcl-2.

PMID- 14572899
TI  - The association of cyclin A and cyclin kinase inhibitor p21 in response to gamma
      irradiation requires the CDK2 binding region, but not the Cy motif.
AB  - The cyclin kinase inhibitor p21 associates with and inhibits cyclin-CDKs to
      retard the progress of the cell cycle in response to DNA damage. The recognition
      sites for cyclin binding on the various cell cycle-related molecules have been
      identified as RXL motifs. In the case of p21, the dependence of the Cy1 (18CRRL)
      or Cy2 (154KRRL) motifs on cyclin E, but not on cyclin A has been demonstrated by
      in vitro experiments. In this study, to clarify the mechanism of p21 association
      with cyclin A, we constructed a p21 expression system in mammalian cells. After
      transfection with an expression vector containing cDNA of various p21-mutants,
      cells were irradiated with 10 Gy of gamma-rays to introduce DNA damage, followed
      by quantification of the p21-cyclin A association. The p21-mutant constructs were
      single or multiple deletions in Cy1, Cy2, and the CDK2 binding region, and a
      nonphosphorylatable alanine mutant of the C-terminal phosphorylation site. We
      demonstrated that the association of p21 and cyclin A in response to gamma
      irradiation requires the CDK binding region, 49-71 aa, but not the Cy motifs. We
      believe the mechanism by which p21 inhibits cyclin-CDKs is distinct in each phase
      of the cell cycle. Furthermore, the increase in the association of p21 and cyclin
      A was not correlated with the levels of p21. This suggests that DNA damage
      triggers a signal to the p21 region between 21 and 96 aa to allow cyclin A
      association.

PMID- 14572900
TI  - Endothelial stress by gravitational unloading: effects on cell growth and
      cytoskeletal organization.
AB  - All organisms on Earth have evolved to survive within the pull of gravity.
      Orbital space flights have clearly demonstrated that the absence or the reduction
      of gravity profoundly affects eukaryotic organisms, including man. Because (i).
      endothelial cells are crucial in the maintenance of the functional integrity of
      the vascular wall, and (ii). cardiovascular deconditioning has been described in
      astronauts, we evaluated whether microgravity affected endothelial functions. We
      show that microgravity reversibly stimulated endothelial cell growth. This effect
      correlated with an overexpression of heat shock protein 70 (hsp70) and a down
      regulation of interleukin 1 alpha (IL-1alpha), a potent inhibitor of endothelial
      cell growth, also implicated in promoting senescence. In addition,
      gravitationally unloaded endothelial cells rapidly remodelled their cytoskeleton
      and, after a few days, markedly down-regulated actin through a transcriptional
      mechanism. We hypothesize that the reduction in the amounts of actin in response
      to microgravity represents an adaptative mechanism to avoid the accumulation of
      redundant actin fibers.

PMID- 14572901
TI  - Combination of 3' and 5' IgH regulatory elements mimics the B-specific endogenous
      expression pattern of IgH genes from pro-B cells to mature B cells in a
      transgenic mouse model.
AB  - To ensure the B cell differentiation stage specificity of the intronic Emu
      element and of the locus control region (LCR) that lies downstream of the IgH
      chain locus, we generated transgenic mice harboring a V(H) promoter-GFP reporter
      gene linked to the 3'LCR region and the Emu element. By flow cytometry, GFP(+)
      lymphocytes were observed amongst pro-B cells (B220(+)CD43(+)CD117(+)) and at all
      stages of differentiation up to mature B cells (B220(+)IgM(+)IgD(+)). Expression
      was strictly confined to cells committed to the B lymphocyte lineage as judged by
      the lack of GFP(+)Thy1,2(+) cells (T lymphocytes) and GFP(+)B220(
      )CD117(+)CD43(+) cells (uncommitted lymphohematopoietic progenitors). Therefore,
      the Emu-GFP-3'LCR transgene is not expressed by hematopoietic stem cells, begins
      its expression in pro-B cells and is specifically active at all stages of B cell
      maturation. The combination of 3' and 5' IgH regulatory elements thus appears as
      a potentially useful cassette in transgenes that require a stringent and early B
      lineage-specific expression.

PMID- 14572902
TI  - Role of sialic acid and sulfate groups in cervical mucus physiological functions:
      study of Macaca radiata glycoproteins.
AB  - The influence of charged groups in glycoproteins was investigated to assess their
      effect on the physiological functions of bonnet monkey cervical mucus. The
      macromolecular glycoproteins from peri-ovulatory, midcycle phase cervical mucus
      were treated with Pronase, trypsin and chymotrypsin and the enzyme-resistant
      glycoproteins purified by gel filtration on Sepharose 4B and a high molecular
      weight component containing carbohydrates, proteins and sulfate groups was
      recovered in high yield. This material still reacted with an antiserum directed
      against purified midcycle glycoprotein but not against another antiserum directed
      against luteal phase purified glycoproteins. Upon treatment with Pronase, trypsin
      and chymotrypsin, asialoglycoproteins and desulfated asialoglycoproteins released
      fragments of low molecular sizes, none of which reacted with the anti-midcycle
      glycoprotein antiserum. Cervical mucus collected from the estrogenic phase
      displayed a morphology supporting sperm migration, and this mucus retains the
      same morphology and reacts with the anti-midcycle glycoprotein antiserum
      following mild treatment with sialidase and subsequently with Pronase. These
      results imply that charged carbohydrate groups help maintain the structural and
      functional integrity of the mucus glycoprotein in its biological environment.

PMID- 14572903
TI  - Transacetylations to carbohydrates catalyzed by acetylxylan esterase in the
      presence of organic solvent.
AB  - Various conditions were applied to test the ability of acetylxylan esterase
      (AcXE) from Schizophyllum commune to catalyze acetyl group transfer to methyl
      beta-D-xylopyranoside (Me-beta-Xylp) and other carbohydrates. The best
      performance of the enzyme was observed in an n-hexane-vinyl acetate-sodium
      dioctylsulfosuccinate (DOSS)-water microemulsion at a molar water-detergent ratio
      (w(0)) of about 4-5. Although the enzyme was found to have a half-life of about 1
      h in the system, more than 60% conversion of Me-beta-Xylp to acetylated
      derivatives was achieved. Under identical reaction conditions, the enzyme
      acetylated other carbohydrates such as methyl beta-D-cellobioside (Me-beta-Cel),
      cellotetraose, methyl beta-D-glucopyranoside (Me-beta-Glcp), 2-deoxy-D-glucose, D
      mannose, beta-1,4-mannobiose, -mannopentaose, -mannohexaose, beta-1,4-xylobiose
      and -xylopentaose. This work is the first example of reverse reactions by an
      acetylxylan esterase and a carbohydrate esterase belonging to family 1.

PMID- 14572905
TI  - 1,5-Anhydroglucitol stimulates insulin release in insulinoma cell lines.
AB  - Concentrations of 1,5-anhydroglucitol (1,5-AG), which is a major circulating
      polyol, decrease in patients with diabetes mellitus. In both insulinoma-derived
      RINr and MIN6 cells, 1,5-AG stimulated insulin release within the range of 0.03
      0.61 mM in a dose-dependent manner. Insulin release was maximally stimulated by
      1,5-AG to levels that reached 25% and 100% greater than that of control (1,5-AG
      free group) in RINr and MIN6 cells, respectively. A physiological concentration
      of 1,5-AG stimulated insulin release after a 5-min incubation and this action was
      maintained for 60 min. In addition, at approximately 1/200 the concentration of
      glucose, 1,5-AG had additive action with 20 mM glucose. The action of 1,5-AG on
      insulin secretion with other types of saccharides and polyol was similarly
      additive. Mannnoheptulose and diazoxide suppressed the stimulative action of 1,5
      AG on insulin release. The secretagogue action of 1,5-AG seemed to be independent
      on an increase in the intracellular content of cAMP and ATP. These results
      suggest that 1,5-AG can stimulate insulin secretion through a mechanism that
      completely differs from that of glucose.

PMID- 14572904
TI  - Characterization of the major allergens purified from the venom of the paper wasp
      Polistes gallicus.
AB  - Allergic reactions to vespid stings are one of the major causes of IgE-mediated
      anaphylaxis. Vespa and Vespula venoms are closely related; Polistes venom is more
      distantly related and its allergens are less well studied. There is limited cross
      reactivity between Polistes and the other vespid venoms because of differences in
      the epitopes on the allergen molecules. In this study, the major allergens of
      Polistes gallicus are isolated and characterized. P. gallicus venom contains four
      major allergens: phospholipase, antigen 5 (Ag5), hyaluronidase and protease that
      were characterized by mass spectrometry and specific binding to IgE. The complete
      amino acid sequence of Ag5 and the sequence of the N-terminal region of
      phospholipase were also determined. The alignment of Ag5 from P. gallicus
      (European species) and Polistes annularis (American species) shows an 85%
      identity that increases to 98% within the same subgenus. This could suggest the
      presence of specific epitopes on Ag5 molecule being the variations on the
      superficial loops. The features of the P. gallicus allergens could explain the
      partial cross-reactivity found between the American and European Polistes venoms,
      and suggest that the use of European Polistes venoms would improve the diagnostic
      specificity and the therapy of European patients and of North American patients
      sensitized by European Polistes.

PMID- 14572906
TI  - The effect of glycation on the structure, function and biological fate of human
      serum albumin as revealed by recombinant mutants.
AB  - Recombinant wild-type human serum albumin (rHSA), the single-residue mutants
      K199A, K439A and K525A and the triple-residue mutant K199A/K439A/K525A were
      produced using a yeast expression system. Portions of the rHSA were glycated to
      different degrees (2.5-250 mM D-glucose). As detected by far-UV and near-UV CD,
      intrinsic tryptophan-fluorescence and probed by 1,1'-bis(4-anilino)naphthalene
      5,5-disulfonic acid, the single-residue mutations had no effect on albumin
      conformation, whereas the triple-residue mutation and glycation caused
      conformational changes. The triple-residue mutation and glycation had comparable
      increased effects on high-affinity binding of warfarin (site I), but decreased
      effects on high-affinity binding of dansylsarcosine (site II) and the esterase
      like activity of albumin. The relation between plasma half-lives in rats were
      found to be glycated rHSA (50 mM glucose)<triple-residue mutated rHSA<rHSA. The
      opposite trend was found for liver and kidney uptakes in mice. Even though the
      functional and the in vivo properties of rHSA could be effected differently by
      the minor conformational changes caused by the triple-residue mutation and
      glycation, the present findings indicate that the effect of glycation can be
      partly explained by blockage of the positive charges of lysine at positions 199,
      439 and 525.

PMID- 14572907
TI  - Nitroglycerin, a nitric oxide generator attenuates ferric nitrilotriacetate
      induced renal oxidative stress, hyperproliferative response and necrosis in ddY
      mice.
AB  - Nitric oxide (NO) is a short lived, readily diffusible intracellular messenger
      molecule associated with multiple organ-specific regulatory functions. In this
      communication, we elucidate the effect of exogenous NO administration, using
      nitroglycerin (GTN), on ferric nitrilotriacetate (Fe-NTA)-induced renal oxidative
      stress, hyperproliferative response and necrosis in ddY mice. Fe-NTA is a known
      complete renal carcinogen as well as renal and hepatic tumor promoter, which act
      by generating oxidative stress in the tissues. GTN treatment to ddY mice prior to
      Fe-NTA administration resulted in a highly significant protection against Fe-NTA
      induced renal oxidative stress, hyperproliferative response and necrosis. In
      oxidative stress protection studies, the decrease in the level of renal
      glutathione and antioxidant enzyme activities induced by Fe-NTA were
      significantly reversed by GTN pretreatment in a dose-dependent manner (12-46%
      recovery, P<0.05-0.001). GTN pretreatment also resulted in a dose-dependent
      inhibition (24-39% inhibition, P<0.05-0.001) of Fe-NTA-induced lipid peroxidation
      as measured by TBARS formation in renal tissues. Similarly, in hyperproliferation
      protection studies, GTN pretreatment showed a strong inhibition of Fe-NTA-induced
      renal ornithine decarboxylase (ODC) activity (51-57% inhibition, P<0.001) and
      [3H]thymidine incorporation (43-58% inhibition, P<0.001) into renal DNA. GTN
      pretreatment almost completely prevented kidney biomolecules from oxidative
      damage and protected the tissue against the observed histopathological
      alterations. From this data, it can be concluded that exogenously produced NO
      from GTN might scavenge reactive oxygen species (ROS) and decreases toxic
      metabolites of Fe-NTA and thereby inhibiting renal oxidative stress. In addition,
      exogenously produced NO can also inhibit Fe-NTA-induced hyperproliferative
      response by down-regulating the activity of ODC and the rate of [3H]thymidine
      incorporation into renal DNA and could be suggested as another possible clinical
      application for this NO-donor (GTN, traditionally used as a vasodilator) in
      oncological medicine.

PMID- 14572908
TI  - Alternative pathway for the formation of 4,5-dihydroxy-2,3-pentanedione, the
      proposed precursor of 4-hydroxy-5-methyl-3(2H)-furanone as well as autoinducer-2,
      and its detection as natural constituent of tomato fruit.
AB  - The formation of 4-hydroxy-5-methyl-3(2H)-furanone (HMF, norfuraneol) by spinach
      ribosephosphate isomerase was reinvestigated. Incubation experiments using D
      ribose-5-phosphate and D-ribulose-5-phosphate clearly revealed a spontaneous
      nonenzymatic formation of the hydroxy-furanone from the ketose-phosphate under
      physiological conditions at 35 degrees C and pH 7.5, whereupon up to 1.3% of D
      ribulose-5-phosphate was transformed to HMF within 15 h. 4,5-Dihydroxy-2,3
      pentanedione was deduced as ultimate precursor of HMF, since addition of o
      phenylenediamine to the incubation mixture led to lower amounts of HMF and to the
      formation of 3-(1,2-dihydroxyethyl)-2-methylquinoxaline, which was identified by
      means of high pressure liquid chromatography with diode array detection (HPLC
      DAD), HPLC-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) and
      NMR spectroscopy. Additionally, the spontaneous formation of 4,5-dihydroxy-2,3
      pentanedione was demontrated by its conversion to the respective alditol acetate
      using either NaBH(4) or NaBD(4) for the reduction. Comparative gas chromatography
      mass spectrometry (GC-MS) analysis revealed the incorporation of two deuterium
      atoms and confirmed the dicarbonyl structure. Application of 1-13C-D-ribulose-5
      phosphate as well as 5-13C-D-ribulose-5-phosphate and analysis of the derived
      quinoxaline derivatives by HPLC-ESI-MS/MS demonstrated the formation of the
      methyl-group at C-5 of the carbohydrate phosphate in consequence of a
      nonenzymatic phosphate elimination. Application of o-phenylenediamine into ripe
      tomatoes led to the detection of 3-(1,2-dihydroxyethyl)-2-methylquinoxaline by
      means of HPLC-MS/MS analysis implying the genuine occurrence of 4,5-dihydroxy-2,3
      pentanedione in this fruit.

PMID- 14572909
TI  - Suppression of apolipoprotein AI gene expression in HepG2 cells by TNF alpha and
      IL-1beta.
AB  - Plasma inflammatory cytokines are elevated in obese subjects as well as in those
      with type 2 diabetes. This presumably results in systemic insulin resistance,
      characterized by a pro-atherogenic plasma lipid profile and reduced
      apolipoprotein AI (apoAI) protein levels. To determine how cytokine-mediated
      insulin resistance suppresses apoAI gene expression, we investigated the effect
      of tumor necrosis factor alpha (TNF alpha) and interleukin-1beta (IL-1beta) on
      apoAI protein, mRNA, and transcriptional activity in the human hepatoma cell line
      HepG2. ApoAI secretion was suppressed in a dose-dependent manner in HepG2 cells
      treated with both cytokines. ApoAI protein levels were 2892+/-22.0, 2263+/-117,
      2458+/-25.0, 3401+/-152, 2333+/-248, 1520+/-41.5 and 956.0+/-11.0 arbitrary units
      (AU) in cells treated with 0, 0.3, 1.0, 3.0, 10, 30, and 100 ng/ml TNF alpha,
      achieving statistical significance in the 30 and 100 ng/ml range (P<0.0009).
      ApoAI protein levels were 4055+/-360, 3697+/-101, 3347+/-327, 1561+/-33.0, 1581+/
      182, 810.0+/-59.5, and 1766+/-717 AU in cells treated with similar doses of IL
      1beta, achieving statistical significance within the range of 3-100 ng/ml
      (P<0.02). ApoAI mRNA levels were suppressed 50.8% in HepG2 cells treated with 30
      ng/ml TNF alpha for 24 h (P<0.05), and remained suppressed for up to 96 h.
      Similarly, treatment of cells with 30 ng/ml IL-1beta for 24 h, resulted in 42.9%
      reduction in apoAI mRNA levels (P<0.05) and remained suppressed for up to 96 h.
      In order to determine if the effect of TNF alpha and IL-1beta occurs at the
      transcriptional level, HepG2 cells were transfected with a chloramphenicol
      acetyltransferase (CAT) reporter gene plasmid containing the full-length apoAI
      promoter, and after 24 h, treated with TNF alpha (30 ng/ml), IL-1beta (30 ng/ml),
      or both cytokines. CAT activity was suppressed by both cytokines (24.0+/-1.9%
      acetylation in control cells vs. 5.6+/-1.2% (P<0.0004), 10.2+/-1.5% (P<0.0006),
      and 3.9+/-0.9% acetylation (P<0.0002) in cells treated with TNF alpha, IL-1beta,
      and the combination of both cytokines, respectively) suggesting that cytokine
      mediated suppression occurs at the transcriptional level. Using a series of apoAI
      deletion constructs, the cytokine response element was mapped between nucleotides
      -325 and -186 (relative to the transcriptional start site). This region contains
      a previously identified and characterized cis-element, site A, which binds
      several different transcription factors. Finally, electrophoretic mobility shift
      assays (EMSA) showed that TNF alpha treatment of HepG2 cells is associated with
      reduced nuclear factor binding to site A. These studies suggest that inflammatory
      cytokines down-regulate apoAI expression at least partly through inhibition of
      binding of the nuclear factors to site A of the apoAI promoter.

PMID- 14572910
TI  - Chemoattractant-stimulated calcium influx in Dictyostelium discoideum does not
      depend on cGMP.
AB  - Chemoattractant stimulation of Dictyostelium cells leads to the opening of
      calcium channels in the plasma membrane, causing extracellular calcium to flux
      into the cell. The genetically uncharacterised mutants stmF and KI8 show strongly
      altered chemoattractant-stimulated cGMP responses. The aberrant calcium influx in
      these strains has provided evidence that the chemoattractant-stimulated calcium
      influx is potentiated by cGMP. We have tested this hypothesis in genetically
      defined mutants by measuring the calcium influx in a strain that lacks
      intracellular cGMP due to the disruption of two guanylyl cyclases, and in a
      strain with increased cGMP levels caused by the disruption of two cGMP-degrading
      phosphodiesterases. The results reveal that the calcium influx stimulated by cAMP
      or folic acid is essentially identical in these strains. We conclude that cGMP is
      not involved in chemoattractant-stimulated calcium influx.

PMID- 14572911
TI  - Expression changes in mRNAs and mitochondrial damage in lens epithelial cells
      with selenite.
AB  - An overdose of sodium selenite induces cataracts in young rats. The mid-stage
      events producing the cataract include calpain-induced hydrolysis and
      precipitation of lens proteins. Apoptosis in lens epithelial cells has been
      suggested as an initial event in selenite cataracts. Expression levels of two
      genes associated with apoptosis were altered in lens epithelial cells from
      selenite-injected rats. The purpose of the present experiment was to perform a
      more comprehensive search for changes in expression of mRNAs in lens epithelial
      cells in order to more fully delineate the early events in selenite-induced
      cataracts. Lens epithelial cells were harvested at 1 and 2 days after a single
      subcutaneous injection of sodium selenite (30 mumol/kg body weight) into 12-day
      old rats. Gene expression was analyzed using a commercial DNA array (Rat Genome
      U34A GeneChip array, Affymetrix). Of approximately 8000 genes assayed by
      hybridization, 13 genes were decreased and 27 genes were increased in the rat
      lens epithelial cells after injection of selenite. Some of the up-regulated genes
      included apoptosis-related genes, and a majority of the down-regulated genes were
      mitochondrial genes. Previously observed changes in expression of EGR-1 mRNA were
      also confirmed. Changes in the expression patterns of mRNAs were also confirmed
      by RT-PCR. To determine the mechanism for damage of lens epithelial cells (alpha
      TN4 cell) by culture in selenite, leakage of cytochrome c from mitochondria was
      measured. Selenite caused significant leakage of cytochrome c into the cytosol of
      alpha TN4 cells. Our data suggested that the loss of integrity of lens epithelial
      cells by selenite might be caused by preferential down-regulation of
      mitochondrial RNAs, release of cytochrome c, and impaired mitochondrial function.
      Up-regulation of mRNAs involved in maintenance of DNA, regulation of metabolism,
      and induction of apoptosis may also play roles.

PMID- 14572912
TI  - Characterization of the N-terminal domain of NrtC, the ATP-binding subunit of ABC
      type nitrate transporter of the cyanobacterium Phormidium laminosum.
AB  - The N-terminal domain of NrtC, the ATP-binding subunit of nitrate/nitrite ABC
      transporter in the cyanobacterium Phormidium laminosum, has been expressed in
      Escherichia coli as a histidine-tagged fusion protein (His(6)NrtC1). Binding of
      ATP to the pure His(6)NrtC1 was characterized using the nucleotide analogue TNP
      ATP [2'(3')-O-(2,4,6-trinitrophenyl) adenosine 5'-triphosphate]. Fluorescence
      assays showed that His(6)NrtC1 specifically binds Mg(2+) TNP-ATP with high
      affinity, binding being dependent on protein concentration. The presence of ATP
      prevents the covalent modification of His(6)NrtC1 by fluorescein 5'
      isothiocyanate (FITC), suggesting that this probe reacts at the nucleotide
      binding site of NrtC. The active form of the truncated NrtC is a dimer that shows
      high affinity for TNP-ATP (K(d)=0.76+/-0.1 microM). Evidence for the presence of
      two nucleotide-binding sites per dimer protein is given. Our results indicate
      that nucleotide binding is strongly dependent on the dimerization of NrtC and
      that the N-terminal domain of the protein contains the binding site for ATP. No
      ATPase activity catalyzed in vitro by the truncated subunit was detected.

PMID- 14572913
TI  - Neuroepithelial secondary organizers and cell fate specification in the
      developing brain.
AB  - In vertebrates, elaborate cellular interactions regulate the establishment of the
      complex structural pattern of the developing central nervous system. Distinct
      neural and glial identities are acquired by neuroepithelial cells, through
      progressive restriction of histogenetic potential under the influence of local
      environmental signals. The localization of the sources of such morphogenetic
      signals in discrete domains of the developing neural primordium has led to the
      concept of secondary organizers which refine the identity and polarity of
      neighboring neuroepithelial regions. Thus, these organizers, secondary to those
      that operate throughout the embryo during gastrulation, act to pattern the
      anterior neural plate and tube giving rise to the forebrain, midbrain and
      hindbrain vesicles. Important progress has recently been made in understanding
      their genesis and function.

PMID- 14572914
TI  - Steroid hormone modulation of olfactory processing in the context of socio-sexual
      behaviors in rodents and humans.
AB  - Primer pheromones and other chemosensory cues are important factors governing
      social interactions and reproductive physiology in many species of mammals.
      Responses to these chemosignals can vary substantially within and between
      individuals. This variability can stem, at least in part, from the modulating
      effects steroid and non-steroid hormones exert on olfactory processing. Such
      modulation frequently augments or facilitates the effects that prevailing social
      and environmental conditions have on the reproductive axis. The mechanisms
      underlying the hormonal regulation of responses to chemosensory cues are diverse.
      They are in part behavioral, achieved through the modulation of
      chemoinvestigative behaviors, and in part a product of the modulation of the
      intrinsic responsiveness of the main and accessory olfactory systems to
      conspecific, as well as other classes, of chemosignals. The behavioral and non
      behavioral effects complement one another to ensure that mating and other
      reproductive processes are confined to reproductively favorable conditions.

PMID- 14572915
TI  - Pathogenesis of cerebral amyloid angiopathy.
AB  - Cerebral amyloid angiopathy (CAA) is the result of the deposition of an
      amyloidogenic protein in cortical and leptomeningeal vessels. The most common
      type of CAA is caused by amyloid beta-protein (Abeta), which is particularly
      associated with Alzheimer's disease (AD). Excessive Abeta-CAA formation can be
      caused by several mutations in the Abeta precursor protein and presenilin genes.
      The origin of Abeta in CAA is likely to be neuronal, although cerebrovascular
      cells or the circulation cannot be excluded as a source. Despite the apparent
      similarity, the pathogenesis of CAA appears to differ from that of senile plaques
      in several aspects, including the mechanism of Abeta-induced cellular toxicity,
      the extent of inflammatory reaction and the role of oxidative stress. Therefore,
      therapeutic strategies for AD should, at least in part, also target CAA.
      Moreover, CAA and cerebrovascular disease (CVD) may set a lower threshold for AD
      like changes to cause dementia and may even cause dementia on its own, since
      patients with AD and CAA and/or CVD appear to be more cognitively impaired than
      patients with only AD. In conclusion, the precise impact of CAA on AD or dementia
      remains unclear, however, its role may have been underestimated in the past, and
      more extensive studies of in vitro and in vivo models for CAA will be needed to
      elucidate the importance of CAA-specific approaches in designing intervention
      strategies for AD.

PMID- 14572916
TI  - A relation between rest and the self in the brain?
AB  - Neuroimaging techniques such as positron emission tomography (PET) and functional
      magnetic resonance imaging (fMRI) are widely used to identify the cerebral
      correlates of cognitive tasks. The resting state presents the advantage to serve
      as a reference in all experiments but is also an ill-defined mental state because
      it may vary both from one subject to another and within the same subject. The
      most challenging question concerns the areas whose activity (revealed by PET or
      fMRI imaging) is greater in rest state than in an active condition. The present
      work reports the result of a meta-analysis including five previously published
      studies. The five different tasks involved are the following: attribution of
      intention, judgement of stimulus pleasantness, discrimination of spatial
      attributes, judgement of other peoples' belief and perception of gaze. For each
      study, the general linear model was used to assess statistical difference and a
      contrast resting state minus other conditions was calculated. The intersection of
      the five contrasts was used to search for the variation jointly observed across
      the different experiments. This lead to a reduced number of clusters: one cluster
      in the lower/anterior part of the cingulate gyrus and four clusters located in
      the medial/superior frontal gyrus, along the superior frontal sulcus. We discuss
      the location of these areas with respect to the location of activations induced
      by different tasks: externally focused attention, memory, general reasoning,
      theory of mind and self-referential tasks. We observed that medial prefrontal
      cortex exhibits a lower activity when the subject's attention is focused towards
      the external world than when the subject has to additionally refer to some
      internal states. By contrast, this activity is greater during resting state than
      during both externally directed and internally directed attention. Thus, we
      hypothesize that during rest, the subject is in a state where he refers only to
      his own self.

PMID- 14572917
TI  - Gender and the social context of smoking behaviour.
AB  - This paper examines the relative effect of both individual and societal factors
      that impinge directly on smoking behaviour of women and men. The societal factors
      are cigarettes price, tobacco control legislation, newspaper coverage of tobacco
      issues, overall economic factors, and social milieu characteristics. Three
      Canadian provinces are studied, from 1978 to 1995. A repeated cross-section
      design is used. Data are derived from national surveys and official documents.
      Results show that smoking occurs in social contexts within which the price of
      cigarettes appears to have a significant negative impact on the prevalence of
      smoking and the quantity of cigarettes smoked by men, but no effect on either the
      prevalence of smoking or the amount smoked by women. More comprehensive and
      restrictive no-smoking legislation and legislation on youth access to tobacco
      influence negatively the prevalence of smoking both for men and women. However,
      these laws do not have the same effects on the number of cigarettes smoked by
      women and men. Newspaper articles on the other hand, negatively influence smoking
      prevalence for women and men. As differences are observed in the responsiveness
      of men and women to tobacco control policies, policymakers and practitioners need
      to keep in mind that tobacco control policies have to be tailored to the broader
      context of the lives of women and men. Future work needs also to be done to
      clarify the interrelationships between social influences on smoking such as
      price, laws and media, and the relationships between these and intrapersonal and
      interpersonal factors, as well as other social and cultural factors.

PMID- 14572918
TI  - Public place restrictions on smoking in Canada: assessing the role of the state,
      media, science and public health advocacy.
AB  - While much is known about the impact of law and public policy, we know
      considerably less about their antecedents. Theories of policy adoption suggest
      that a variety of policy inputs help to shape legislative change. This research
      considers the enactment of municipal smoking bylaws in Canada between 1970 and
      1995. The emergence of second-hand smoke (SHS) has been offered as a viable
      explanation for the increased enactment of local smoking restrictions. A number
      of indicators confirm the rising public health concern around SHS. Using Health
      Canada data on municipal smoking bylaw enactment in Canada, this paper employs an
      event history analysis to trace the role of four indicators of the increased
      recognition of SHS as a public health concern-scientific research, parliamentary
      debate, print media, and health advocacy. Findings indicate that the print media
      and health advocacy play the strongest role in explaining the increase in the
      adoption of municipal smoking bylaws in Canada. Results lend support to the
      quantitative study of the policy adoption process and to theories of policy
      making that consider multiple influences on policy adoption.

PMID- 14572919
TI  - Putting policy into practice? Poverty and people with serious mental illness.
AB  - This paper addresses the effects of chronic poverty on people with serious mental
      illness. More specifically, we are concerned with the extent to which welfare
      restructuring, by deepening the poverty facing people with serious mental
      illness, undermines the expressed intent of mental health policy to improve the
      quality of life (QOL) of this population. The province of Ontario in Canada forms
      the setting for the study. The paper first examines recent trends in mental
      health care and social assistance policy in Ontario. While income support is
      consistently recognized as a core element of mental health care, welfare
      restructuring has led to a significant decline in the real value of income
      supports received by people with serious mental illness. The paper then examines
      the implications of this trend for the QOL of residential care facility tenants
      in Hamilton, Ontario. Here, the case study is explicitly connected to QOL
      scholarship. In addition, the study is grounded in an analysis of the broader
      transformation of the welfare state in Ontario. Interview data suggest that
      tenants experience chronic poverty that has a deleterious impact on multiple life
      domains including basic needs, family, social relations, leisure and self-esteem.
      Implications for research and policy are discussed.

PMID- 14572920
TI  - Beyond the income inequality hypothesis: class, neo-liberalism, and health
      inequalities.
AB  - This paper describes and critiques the income inequality approach to health
      inequalities. It then presents an alternative class-based model through a focus
      on the causes and not only the consequences of income inequalities. In this
      model, the relationship between income inequality and health appears as a special
      case within a broader causal chain. It is argued that global and national socio
      political-economic trends have increased the power of business classes and
      lowered that of working classes. The neo-liberal policies accompanying these
      trends led to increased income inequality but also poverty and unequal access to
      many other health-relevant resources. But international pressures towards neo
      liberal doctrines and policies are differentially resisted by various nations
      because of historically embedded variation in class and institutional structures.
      Data presented indicates that neo-liberalism is associated with greater poverty
      and income inequalities, and greater health inequalities within nations.
      Furthermore, countries with Social Democratic forms of welfare regimes (i.e.,
      those that are less neo-liberal) have better health than do those that are more
      neo-liberal. The paper concludes with discussion of what further steps are needed
      to "go beyond" the income inequality hypothesis towards consideration of a
      broader set of the social determinants of health.

PMID- 14572921
TI  - Area effects on health variation over the life-course: analysis of the
      longitudinal study sample in England using new data on area of residence in
      childhood.
AB  - There is a growing literature which demonstrates that (a) conditions throughout
      the life-course are important for health outcomes in older people and (b)
      "contextual" conditions in the place of residence, as well as individual
      characteristics influence health variations. This paper contributes to this
      debate by presenting results of an analysis of data from the Office for National
      Statistics Longitudinal Study (LS) for England and Wales. The analysis makes use
      of a new set of variables, which have been added to the LS, describing the social
      and economic conditions in the 1930s in residential areas where members of the LS
      sample were registered as living in 1939. The analysis focuses on people who were
      aged 0-16 in 1939. The health outcomes considered are death between 1981 and
      1991, and for those still living, whether long-term illness was reported in the
      1991 census. Regression analysis is used to examine the effects of residence in
      1981, and data on the registered place of residence in 1939. The analysis shows
      that individual characteristics and type of area of residence in 1981 were
      associated with health outcomes. In addition, some variables describing socio
      economic conditions in the 1930s contribute independently to the regression
      models (notably measures of economic deprivation and unemployment). The results
      suggest that conditions in residential area in early life may help to explain
      relatively poor health experience of populations in some parts of Britain today.

PMID- 14572922
TI  - Health, place and childhood asthma in southwest Alaska.
AB  - Social science theories of health and place posit that individuals perceive a
      relationship between characteristics of the geographic location in which they
      reside and their health, well-being, and self-identity. A number of ethnographies
      of health and place have studied how urban and suburban populations impacted by
      industrial pollution or waste have come to perceive a link between rates of
      cancer and their unhealthy environment. There has been little study of the
      applicability of the health and place framework to community perceptions of long
      term chronic illness. This paper examines the asthma perceptions of Yup'ik
      parents of asthmatic children using data from semi-structured ethnographic
      interviews conducted in five villages and one town of the Yukon-Kuskokwim delta
      of southwest Alaska. Informants cited local climatic features, large-scale
      changes of the last 30 years to the village built landscape, and ongoing
      conditions of substandard housing and sanitation as etiological factors
      associated with childhood asthma. Our study suggests the need for further
      research concerning lay perceptions of one aspect of the epidemilogic transition
      the association between chronic illness and place, especially in rural
      communities undergoing dramatic developmental change.

PMID- 14572924
TI  - Sickness absence and early retirement at two workplaces--effects of
      organisational intervention in Sweden.
AB  - This study sought to compare sickness absence and early retirement at two
      workplaces in Sweden before and after they had received financial support from
      the Working Life Fund and implemented vocational rehabilitation activities. Two
      paper and pulp manufacturing plants were compared and a cohort study was set up.
      The cohort included everyone born in 1934 or later who was employed in December
      1988 (918 employees at Plant A and 1543 at Plant B). For 10 years (1989-98), sick
      leave and disability pensions were monitored. The periods before and after the
      intervention (1989-93 and 1994-98, respectively) were compared. Cumulative
      incidence was calculated for short-, long-term and very long-term sick leave,
      company pension and early retirement. There was no difference between the plants
      in terms of the three different outcomes when sick leave was measured before and
      after the intervention. Sick leave in Period 1 was strongly correlated with an
      elevated risk of sick leave in Period 2. The cumulative incidence of short-term
      sick leave decreased from 0.92 (95% CI, 0.91-0.93) in Period 1 to 0.79 (95% CI,
      0.77-0.80) in Period 2. For employees in the upper age groups, relative risk for
      long-term and very long-term sick leave was elevated in both periods. The
      incidence of early retirement and company pension differed between the companies.
      We conclude that the size of financial investments in rehabilitation programmes
      has no significant impact on sickness absence or disability pension, based on a
      comparison between two paper and pulp manufacturing plants in Sweden during the
      early 1990s.

PMID- 14572923
TI  - The drug industry and medical practice--the case of menopausal hormone therapy in
      Estonia.
AB  - After the dissolution of the Soviet Union, Estonia quickly adopted a market
      economy. In medicine this has included the uptake of western-style health care
      and drug promotion aimed at practising physicians. Using post-menopausal hormone
      therapy (HT) as an example, we studied the consequences of this natural
      experiment on prescribing and on physicians' opinions of HT and drug promotion.
      Data were obtained from a cross-sectional questionnaire survey sent to
      gynaecologists and family practitioners (FPs) in 2000 compared to an earlier
      Finnish survey, and from drug sales figures (based on defined daily doses), local
      medical journals and observations. The survey focussed on physicians' opinions of
      HT, HT information and HT education, and was sent to a random sample of 500
      physicians, of whom 68% responded. The sales of HT drugs in the 1990s in Estonia
      were much lower than in Finland, but rapidly rose during that decade. Physicians
      considered drug advertising to be a factor contributing to the increased HT use.
      Most gynaecologists but fewer FPs reported that they had had enough continuing
      education on menopause and HT. For 39% of the gynaecologists and 20% of the FPs,
      (part of) the costs to attend their last education activity was paid by a drug
      firm. Respondents who wished for further education considered drug firms to be
      potential organisers. Gynaecologists had had more communication on HT with the
      drug industry, and their attitudes towards HT were more positive than those of
      FPs. Fears about cancer in the 1980s were not found in 2000. The study suggests
      that the drug industry contributed to the change in physicians' views of HT.

PMID- 14572925
TI  - Religion and preventative health care utilization among the elderly.
AB  - Evidence supporting a relationship between religion and physical health has
      increased substantially in the recent past. One possible explanation for this
      relationship that has not received much attention in the literature is that
      health care utilization may differ by religious involvement or religious
      denomination. A nationally representative sample of older adults was used to
      estimate the effects of religious salience and denomination on six different
      types of preventative health care (i.e. flu shots, cholesterol screening, breast
      self-exams, mammograms, pap smears, and prostate screening). Findings show that
      both men and women who report high levels of religiosity are more likely to use
      preventative services. Denominational differences show that affiliated
      individuals, especially those who are Jewish, are significantly more likely to
      use each type of preventative care than non-affiliated individuals. The results
      of this study open the door to further exploration of this potentially important,
      but relatively neglected, link between religion and health.

PMID- 14572926
TI  - Changing health inequalities in east and west Germany since unification.
AB  - The unification of Germany in 1990 brought about substantial social and economic
      changes in its eastern part, with new uncertainties and, despite increasing
      overall income, rising inequality. This paper explores the potential impact on
      health of these changes during the 1990s, looking specifically at income-related
      health inequalities in east and west Germany and its modulation by psychosocial
      factors. We used data from the German Socio-Economic Panel (GSOEP) for the years
      1992 and 1997, including individuals aged 25+. We investigated changes in self
      perceived health in the two parts of Germany and its socio-economic and
      psychosocial determinants. Analyses estimated odds ratios of less than good
      health using logistic regression. In 1992, 47% of east Germans rated their health
      worse than good compared with 54% in the west. By 1997, the east-west gap in self
      rated health had disappeared, with the prevalence of poor health increasing to
      56% in both parts. Income and education were important determinants of health in
      east and west, with, in the age-sex-adjusted model, those having available less
      than 60% of median equivalent income being at increased risk of poor health in
      1992 (OR(east) 2.39, 1.45-3.94; OR(west) 2.04, 1.65-2.52). Addition of education
      reduced the strength of this relationship only slightly. In the west, income
      related health inequalities widened between 1992 and 1997 yet the initially
      stronger gradient declined in the east, despite an overall increase in income
      inequality (OR(east) 1.63, 1.04-2.56; OR(west) 2.65, 2.19-3.21). The impact of
      education remained stable. Psychosocial variables were important determinants,
      mediating the effects of income, with leisure-cultural social involvement
      exerting the strongest effect in both east and west.The results show that, unlike
      in the west, the overall increase in income inequality in east Germany between
      1992 and 1997 was not accompanied by a simultaneous increase in income-related
      health inequalities. This suggests that mechanisms involved in the association of
      socio-economic factors and health possibly behave differently in east and west.

PMID- 14572927
TI  - Predictive genetic test decisions for Huntington's disease: context, appraisal
      and new moral imperatives.
AB  - Predictive testing is one of the new genetic technologies which, in conjunction
      with developing fields such as pharmacogenomics, promises many benefits for
      preventive and population health. Understanding how individuals appraise and make
      genetic test decisions is increasingly relevant as the technology expands. "Lay"
      understandings of genetic risk and test decision-making, located within holistic
      life frameworks including family or kin relationships, may vary considerably from
      clinical representations of these phenomena. The predictive test for Huntington's
      disease (HD), whilst specific to a single-gene, serious, mature-onset but
      currently untreatable disorder, is regarded as a model in this context. This
      paper reports upon a qualitative Australian study which investigated predictive
      test decision-making by individuals at risk for HD, the contexts of their
      decisions and the appraisals which underpinned them. In-depth interviews were
      conducted in Australia with 16 individuals at 50% risk for HD, with variation
      across testing decisions, gender, age and selected characteristics. Findings
      suggested predictive testing was regarded as a significant life decision with
      important implications for self and others, while the right "not to know" genetic
      status was staunchly and unanimously defended. Multiple contexts of reference
      were identified within which test decisions were located, including intra- and
      inter-personal frameworks, family history and experience of HD, and temporality.
      Participants used two main criteria in appraising test options: perceived value
      of, or need for the test information, for self and/or significant others, and
      degree to which such information could be tolerated and managed, short and long
      term, by self and/or others. Selected moral and ethical considerations involved
      in decision-making are examined, as well as the clinical and socio-political
      contexts in which predictive testing is located. The paper argues that
      psychosocial vulnerabilities generated by the availability of testing
      technologies and exacerbated by policy imperatives towards individual
      responsibility and self-governance should be addressed at broader societal
      levels.

PMID- 14572928
TI  - Screening for breast cancer: candidacy and compliance.
AB  - This paper is concerned with understanding why some women accept their invitation
      for free screening mammography and others do not. Free screening mammography is
      offered to women aged 50-64 in Britain. Uptake of invitations is about twice as
      high in leafy suburbs than in inner-city areas. Low uptake in inner-city areas
      has been attributed to "problems" of black and minority ethnic women. The
      research reported here was carried out in Hackney, an inner city London borough
      with an ethnically diverse and socially deprived population. Hackney also has the
      lowest uptake of screening mammography in the country. Twenty focus groups were
      held. Participants included white, black and minority ethnic women. Eight focus
      groups were conducted in English; 12 in other languages. Some methodological
      issues raised by undertaking qualitative research in several languages are
      considered. The research demonstrates how the inclusion of white women in
      research which operationalises ethnicity minimizes the risk of developing an
      analysis focusing on "problems" of black and minority ethnic women and encourages
      the development of general themes which may apply to all women. The analysis
      focuses on candidacy, that is, women's assessment of risk of their disease, and
      compliance, that is, the explanations respondents volunteered for accepting or
      refusing an invitation to attend for mammography. Candidacy and ethnicity emerge
      as similar constructs, manipulated by women to make claims about their risk of
      breast cancer. Other, non-medical reasons were given for compliance which serve
      as a warning about assuming that, when women accept their invitation, they do so
      for same the reasons the architects of the National Health Service Breast
      Screening Programme had in mind.

PMID- 14572929
TI  - Patient activism and the struggle for diagnosis: Gulf War illnesses and other
      medically unexplained physical symptoms in the US.
AB  - We examine Gulf War illnesses--which include the fatigue, joint pain, dermatitis,
      headaches, memory loss, blurred vision, diarrhea, and other symptoms reported by
      Gulf War veterans--in relation to other medically unexplained physical symptoms
      such as multiple chemical sensitivity, chronic fatigue syndrome, and
      fibromyalgia. Our intent is to examine the diagnosis negotiations involved in
      these mysterious diseases, by showing the different forms of legitimacy involved
      in such interactions. Factors involved in diagnostic legitimacy are: diagnostic
      legitimacy in the medical community, lay acceptance of the diagnosis, uncertainty
      in looking for causes, and social mobilization. We conclude by noting that
      research may not be able to find any cause for these diseases/conditions; hence,
      it may be necessary to embrace medical uncertainty, and also to accept patient
      experience in order to facilitate diagnosis, treatment, and recovery process.
      Such a change can alter patients' expectations and taken-for-granted assumptions
      about medicine, and perhaps in turn reduce the frequency with which dissatisfied
      individuals form illness groups that mobilize to challenge what they see as an
      unresponsive medical system.

PMID- 14572930
TI  - What is important to continuity in home care?. Perspectives of key stakeholders.
AB  - In Canada, home care is growing rapidly. Each province takes a somewhat different
      approach to its delivery. Ontario uses a competitive bidding model to award
      contracts to community agencies that bid for service delivery rights. Contracts
      are to be awarded based on quality and price. However, the attributes thought to
      contribute to high quality, such as continuity of care, are not clearly defined
      and are not measured. We sought to identify factors that were important to
      experiencing continuity of care in home care. We interviewed home care clients
      and their caregivers, workers in the home care system (nursing and homemaking
      service providers, case managers) and physicians whose patients use home care.
      During in-depth interviews with these key stakeholders, they described the
      conditions that led to continuity of care in home care. Service providers and
      case managers were also asked about the types of clients who need a high level of
      care continuity. Care that is experienced as running smoothly, that responds to
      clients' needs and requires no special effort for clients to maintain, was seen
      as having continuity. The attributes of care experienced as facilitating
      continuity could be grouped under two dimensions of care-managing care (care
      planning, monitoring and review; and care coordination) and direct service
      provision (uninterrupted service delivery; consistent, appropriate knowledge and
      skills; ongoing accurate observation; trusting relationship between service
      provider and client/caregiver; rapport among team members; and consistent
      timing). Different stakeholders emphasized different attributes of care as most
      important to continuity. Clients included consistency of timing of service
      delivery while rarely mentioning care management issues. They emphasized the
      importance of consistent knowledge and skills in the workers and trusting
      relationships as important to experiencing care continuity. The description of
      attributes of continuity of home care that emerged from this study is compared to
      definitions found in the nursing, mental health and primary care literature.

PMID- 14572931
TI  - Can a brief video intervention improve breast cancer clinical trial knowledge and
      beliefs?
AB  - A total of 262 women in the USA (161 breast cancer survivors and 101 controls)
      were exposed to a video vignette using modeling in which a physician discussed
      the concept of a clinical trial (CT) with a woman who was in the process of
      making a treatment decision. A pretest-post-test design was used and improvements
      in clinical trial knowledge and beliefs were assessed. Results indicate that
      video modeling is a powerful tool for increasing CT knowledge (pretest mean=41.5%
      correct, post-test mean=77.5% correct) but not for improving CT beliefs.
      Increased clinical trial knowledge, as measured by change scores, was associated
      with white race, lower levels of education and pretest breast cancer knowledge,
      more negative pretest CT beliefs, and a higher estimate of the lifetime
      probability that a woman will have breast cancer. When pretest CT knowledge was
      added to the analysis using hierarchical multiple regression, all variables
      except white race became nonsignificant; an increase in CT knowledge was
      associated with having lower pretest CT knowledge. Results indicate that the
      effects of low education, low breast cancer knowledge, and biased probability
      assessment were mediated through the pretest score. An increase in post-test
      positive CT beliefs was associated with older age, thinking about breast cancer
      less often, and having lower pretest CT knowledge in the total sample. When
      pretest CT beliefs was added to the analysis using hierarchical multiple
      regression, all other variables became nonsignificant; an increase in CT beliefs
      was associated with having lower pretest CT beliefs, again indicating mediation
      of the effects of other variables.

PMID- 14572932
TI  - Evidence-based health policy: context and utilisation.
AB  - Evidence-based decision-making is centred on the justification of decisions. In
      the shift from an individual-clinical to a population-policy level, the decision
      making context becomes more uncertain, variable and complex. To address this we
      have developed a conceptual framework for evidence-based decision-making,
      focusing on how context impacts on what constitutes evidence and how that
      evidence is utilised. We present two distinct orientations towards what
      constitutes evidence, representing different relationships between evidence and
      context. We also categorise the decision-making context based on the ways in
      which context impacts on evidence-based decision-making. Furthermore, we invoke
      the concept of axes of evidence-based decision-making to describe the
      relationship between evidence and context as we move from evidence-based medicine
      to evidence-based health policy. From this, we suggest that it may be more
      important how evidence is utilised than how it is defined. Based on the research
      and knowledge utilisation literature, we present a process model of evidence
      utilisation, which forms the basis for the conceptual framework for context-based
      evidence-based decision-making. The conceptual framework attempts to capture the
      role that context plays in the introduction, interpretation and application of
      evidence. We illustrate this framework with examples from policy development for
      colorectal cancer screening.

PMID- 14572937
TI  - Health promotion in a multicultural society.

PMID- 14572938
TI  - When cultures meet in general practice: intercultural differences between GPs and
      parents of child patients.
AB  - Although health care professionals in The Netherlands are increasingly confronted
      with diverse immigrant groups, medical counselling and treatment of these groups
      has not been the subject of extensive research yet. From other studies it is well
      known that intercultural differences can have serious consequences for health
      care, e.g. in terms of risk of incorrect diagnoses or non-compliance. Eighty
      seven autochthonous Dutch and immigrant (mainly from Turkey and Surinam) parents
      of child patients and their general practitioners (GPs) were recruited to
      investigate the influence of cultural differences on mutual understanding and
      patient compliance. Analyses of questionnaires and home interviews revealed that
      there is a relation between the cultural background of the patient and
      effectiveness of communication. Communication in consultations between GPs and
      persons from ethnic minorities is less effective than in consultations with Dutch
      persons: there is more misunderstanding, and also more non-compliance. In
      general, mutual understanding between GP and patient proves to be a strong
      predictor for patient compliance. These findings hold especially true for
      patients living in two worlds, i.e. a mixture of traditional and western
      cultures. The results are discussed in terms of methodological issues and
      practical implications for the health care providers.

PMID- 14572939
TI  - Sociocultural influences on participation in genetic risk assessment and testing
      among African American women.
AB  - The objectives of this observational study were to describe the associations
      between cultural beliefs and values and participation in genetic risk assessment
      and testing among African American women at high risk for having a BRCA1 or BRCA2
      (BRCA1/2) gene alteration. Subjects were 28 high-risk women who self-referred to
      a genetic counseling and testing research program. Overall, 61% subjects received
      BRCA1/2 test results and 39% declined. Mean levels of fatalistic beliefs about
      cancer and future temporal orientation were higher among test acceptors relative
      to decliners. Sociodemographic factors were not associated with test acceptance;
      however, rates of test acceptance were lower among women with greater perceptions
      of familial interdependence (41% versus 91%, P=0.02). The results of this study
      suggest that cultural beliefs and values may influence genetic testing decisions
      among African American women.

PMID- 14572940
TI  - The same but different: clinician-patient communication with gay and lesbian
      patients.
AB  - Surveys estimate that 3-6% of the patients seen by physicians are gay or lesbian.
      There are unique health risks of gays and lesbians that are important to the
      clinician in determining an accurate diagnosis, providing patient education, and
      arriving at an appropriate treatment plan. One of the most significant medical
      risks of these populations includes avoidance of routine health care and
      dissatisfaction with healthcare. Many of these healthcare risks are not addressed
      because of lack of communication based on a number of common assumptions
      including the assumption that the patient is heterosexual. This article includes
      a summary of the medical literature through computerized searches to March 2002
      in MEDLINE, PsychInfo, HEALTHSTAR, and bibliographies in articles on health care
      with gay and lesbian patients. The search strategy included health care of gays
      and lesbians and clinician-patient communication, partner and family issues.
      Secondly, it will examine common communication barriers and provide strategies
      for enhancing communication with patients in a gender-neutral, non-judgmental
      manner including suggestions for enlisting the inclusion of patients' families.

PMID- 14572941
TI  - The illness experiences of patients after a first time myocardial infarction.
AB  - The purpose of this study was to investigate illness experiences of patients
      after a first myocardial infarction (MI), focusing on life situation and the
      recovery process over time. Thirty patients were interviewed within the first 3
      days of hospitalisation, and again 17 weeks after discharge. The interviews were
      tape-recorded verbatim and the transcriptions were analysed and categorised using
      qualitative content analysis. The main category was Uncertainty of the life
      situation that was combined with and articulated the superior theme in both
      interviews. Analyses revealed uncertainty focused on problems related to:
      treatment-seeking behaviour; existential threat; preventing another coronary and
      need for knowledge and support, which the patients considered important for their
      case and future life. The findings are fundamental for the health care when
      education and counselling are planned and challenge health care personnel to
      listen to MI-patients' own experiences.

PMID- 14572942
TI  - Development, content, and process evaluation of a short self-management
      intervention in patients with chronic diseases requiring self-care behaviours.
AB  - Many patients with asthma, diabetes, and heart failure do not succeed in
      integrating the required self-management behaviours into their lives, and fail to
      attain optimal disease control. The purpose of this study was to describe the
      development of a theory-driven intervention to enhance self-management that would
      be appreciated and accepted by participants and providers. Based on self
      regulation theory and proactive coping, the program emphasised goal-setting and
      the planning of behaviour. In five 2h group sessions, participants first decided
      upon their own goal and behaviours they wanted to change. Next, they wrote an
      action-plan to implement these behavioural intentions. Behavioural rehearsal and
      self-monitoring took place between the sessions. Participants and nurse providers
      evaluated the intervention positively. Evaluations were unrelated to patients'
      health at baseline, or to feelings of self-efficacy regarding self-management.
      But patients of older age, lower education, or no current employment responded
      best to the intervention.

PMID- 14572943
TI  - The use of videos to inform smokers about different nicotine replacement
      products.
AB  - This study examined the feasibility of using video presentations to inform
      smokers about nicotine replacement treatment (NRT). The study was part of a
      larger trial comparing four different NRTs. Five hundred and four smokers
      attended a clinic on the day they stopped smoking. They were presented with a
      brief video overview of the four treatments. They were then randomly allocated to
      a treatment and shown another brief video describing that treatment in more
      detail. After 1 week of NRT use, participants rated how clearly the video
      described how the treatments work, how to use them and their possible side
      effects. They also rated how their experience of the product compared to
      expectation in terms of helpfulness, convenience and side effects. The smokers
      reported overwhelmingly that the videos had accurately described the product to
      which they had been allocated. Video presentations can be an effective way to
      convey information to smokers about NRT.

PMID- 14572944
TI  - Feedback based on patient evaluations: a tool for quality improvement?
AB  - Feedback regarding patient evaluations of health care is expected to be a tool
      for quality improvement. This study examined the response of general
      practitioners to such feedback in a randomised trial. Practitioners in the
      intervention group read and discussed the feedback report and then reported on a
      range of actions that can be undertaken to improve the quality of care. Their
      communication behaviour was not found to change. All of the practitioners were
      highly motivated to learn from patient views, both at baseline and after the
      intervention period. Compared to the control group, the practitioners in the
      intervention group had less favourable views of the relevance of patient feedback
      for their practice after the receipt of such feedback. Furthermore, these
      practitioners felt that a patient survey required considerable time and energy
      and saw little reason for change. Although patient feedback can help identify
      areas for improvement, specific barriers must be addressed before such feedback
      can be put to more widespread use.

PMID- 14572945
TI  - Analgesic medication--communication at pharmacies.
AB  - Treatment conducted in co-operation with the client is decisive for a successful
      result i.e. adherence to medication, satisfaction and improved health outcome.
      The aim of this study was to capture the communication between clients and
      pharmacists when dispensing prescriptions of analgesics in community pharmacies.
      The study was based on 42 authentic audio-recordings of clients' communication
      with pharmacists. Most clients had a passive role and the analysis testify to a
      short and asymmetric communication between the interlocutors. On average, the
      clients asked three questions. One-third of these questions were related to
      medication, i.e. dose, effect, written information, symptoms or disease. Of the
      questions asked by pharmacists, 2% were open in character. The study confirms
      previous research in other settings on caregiver dominance in consultations.
      Concordance in pharmaceutical care assumes a much more active client. Therefore
      facilitating a more active role for the clients at pharmacies is of the outmost
      importance.

PMID- 14572946
TI  - AIDS knowledge and educational needs of technical university students in Turkey.
AB  - AIDS is a main health problem of the recent century and is now considered a very
      important cause for mortality and morbidity among young people. The aim of this
      research is to determine the Turkish university students knowledge, sexual risk
      behavior, attitude towards AIDS and educational needs concerning AIDS. A cross
      sectional exploratory design is utilized in this study. One thousand four hundred
      and twenty-seven university new registrants from the Middle East Technical
      University participated and answered a 32-item self-administered questionnaire.
      The questionnaire addressed sociodemographics, sexual risk behavior, self
      assessed knowledge on HIV transmission and AIDS, attitudes towards AIDS infection
      and AIDS patient, source of information and need for AIDS course. The response
      rate was 84%. Two hundred and seventy-one (19%) participants had sexual
      intercourse. Eighty-one (30%) participants reported condom use during the last
      encounter. Seven hundred and twenty-four (51%) stated they knew "very much" about
      AIDS. Students of faculty of engineering (n=384, 69%), economic and
      administrative sciences (n=115, 55%), and architecture (n=42, 52%) declared they
      knew "very much" on AIDS and had a higher frequency as the students from the
      faculty of arts and sciences (n=119, 43%) and education (n=64, 40%). Television
      was reported as the major source of information about AIDS (n=871, 61%). Students
      in faculty of education had lower scores than others (P=0.01). Almost all
      students stated that there should be a course on AIDS in their curriculum.
      Educational and medical institutions are the minor information sources for
      students at universities. Therefore, schools have to integrate new courses on
      AIDS and sexual health in their curricula, physicians caring for these students
      have to take more time for health education.

PMID- 14572947
TI  - The impact of preoperative information on state anxiety, postoperative pain and
      satisfaction with pain management.
AB  - The primary objective of this study was to test whether specific information
      given prior to surgery can help patients obtain better pain relief after total
      knee arthroplasty (TKA). Secondary objectives were to study the impact of
      preoperative information on state and trait anxiety, satisfaction with pain
      management and satisfaction with nursing care. The study was an intervention
      study with two groups of equal size (n=30). The intervention group was given
      specific information while the control group received routine information. Pain
      assessments were made preoperatively and every 3h for the first three
      postoperative days, using the visual analogue scale (VAS). The results of this
      study suggest that information does influence the experience of pain after
      surgery and related psychological factors. The postoperative pain declined more
      rapidly for patients in the treatment group, the degree of preoperative state
      anxiety was lower and they were more satisfied with the postoperative pain
      management.

PMID- 14572948
TI  - Children hospitalized for accidental injuries: Israeli experiences.
AB  - Of the total 411 cases of accidents occurring in the State of Israel during 1999,
      the 314 which were hospitalized at the Edith Wolfson Medical Center, constituting
      7.2% of the total pediatric hospitalizations in that regional hospital, were
      analyzed and summarized. Mean age of the children was 6.6+/-4.4, and ratio of
      boys to girls was 65:35. Accidents were classified by location of occurrence:
      home (52.3%); road (19.3%); sports (17.4%); and school (11.6%). Grades of
      severity were as follows: light (children were discharged without handicaps)
      (13.2%); moderate (children had undergone surgical intervention with prolonged or
      permanent disability) (74%); severe (children were treated in intensive care
      units and had permanent irreversible handicaps) (12.9%). Loss of
      conscientiousness occurred in 13.3% of cases. Affected body parts included: limbs
      (52.7%); head and face (32.7%); spine (7%); and multisystem injury (14.6%). Mean
      duration of hospitalization was 3.1 (+/-2.6 days). Accidental injuries most often
      occurred in the afternoon and in the absence of parental supervision. These
      findings generate conclusions for preventive interventions.

PMID- 14572949
TI  - Characteristics of adolescent attempts to manage overweight.
AB  - This study evaluates the actions taken by obese adolescents in an attempt to lose
      weight in relation to changes in weight. Particular emphasis is put on the
      context surrounding the management process. Thirty one obese adolescents aged 14
      18 participated in this study. The adolescents answered a written questionnaire,
      took a body-size dissatisfaction test and were interviewed. Their family
      physicians were interviewed by telephone. Quantitative data concerned changes in
      weight and body-size dissatisfaction scores. Qualitative analysis included cases
      analyses and building up of synthesis variables. Loss of weight is linked with
      continuity of management attempts as well as with medical follow-up. The most
      frequent management attempt is diet. Self-image is correlated with weight. The
      exclusive emphasis put on diet is discussed in relation to the importance of more
      psychosocial factors such as self-image, denial and attraction to discontinuity.
      Some recommendations for the management of overweight adolescents are then
      outlined.

PMID- 14572952
TI  - Thoughts of a senior neurosurgeon: a message to younger colleagues.

PMID- 14572954
TI  - Intraoperative three-dimensional visualization of the pyramidal tract in a
      neuronavigation system (PTV) reliably predicts true position of principal motor
      pathways.
AB  - BACKGROUND: This prospective study employs anisotropic diffusion-weighted (ADW)
      magnetic resonance imaging for the integration of individual spatial information
      concerning the principal motor pathways into the operating room during
      microneurosurgery in the central region. We hypothesize that the three
      dimensional (3-D) visualization of the pyramidal tract position (PTV) in a
      neuronavigation system based on ADW provides valid information concerning the
      position and extension of the principal motor pathways. METHODS: A total of 13
      consecutive patients with lesions adjacent to the pyramidal tracts and the
      central region underwent microneurosurgery with the help of pyramidal tract
      visualization (PTV). An ADW sequence obtained preoperatively was fused to an
      anatomic navigation sequence. The 3-D reconstructions of the precentral gyrus
      (PG), the pyramidal tract, and the tumor were available in a customized
      neuronavigation system during surgery. Intraoperatively the PG was identified on
      the basis of the aforementioned data. Electric motorcortex stimulation (CS) was
      used to directly verify the PG location and indirectly the fiber tract position.
      RESULTS: In 11 cases (92%) the prediction of the principal motor pathways'
      position was correct. In one case of a meningioma, according to PTV, the tumor
      was falsely localized postcentrally. In the case of a precentral cavernoma, no
      motor response could be elicited by cortical stimulation. CONCLUSION:
      Intraoperative PTV on the basis of ADW provides the neurosurgeon with reliable
      information concerning the position of the principal motor pathways during
      intracranial procedures as proved with intraoperative electrophysiological
      testing. The technique has the potential to reduce operative morbidity. PTV is
      straightforward and can be adapted to other customized neuronavigation devices.

PMID- 14572957
TI  - Apolipoprotein E epsilon4 and the risk of unfavorable outcome after aneurysmal
      subarachnoid hemorrhage.
AB  - BACKGROUND: The APOE-E4 allele has been identified as a risk factor for
      Alzheimer's disease and unfavorable outcomes after brain injuries. The purpose of
      this study was to confirm that APOE allele polymorphism also represents a risk
      factor for unfavorable outcomes following aneurysmal subarachnoid hemorrhage
      (SAH). METHODS: A total of 104 patients with aneurysmal SAH were studied.
      Computed tomography (CT) scan findings of SAH were assessed by Fisher's grade and
      clinical neurologic assessment was performed using the Hunt and Hess (H&H)grading
      system. Serum lipids were also analyzed. Outcomes at 3 months after SAH were
      determined using the Glasgow Outcome Scale. RESULTS: The distributions of APOE
      genotypes and alleles of patients were matched with those of control subjects.
      That 5 of 18 patients with APOE-E4 allele (28%) had an unfavorable outcome was
      significantly different from those without APOE-E4 (8%, chi2, p = 0.032; OR =
      4.34, 95% CI 1.20-15.75). However, the presence or absence of E2 or E3 alleles
      had no significant difference. The relative hazard of APOE-E4 for unfavorable
      outcome exited after adjustment for clinical assessment (OR = 6.95, 95% CI 1.21
      39.75). Total serum cholesterol, low-density lipoprotein and apolipoprotein B
      were elevated in patients with unfavorable rather than favorable outcomes.
      CONCLUSION: Our findings confirmed that the patients with APOE-E4 allele were
      predisposed to unfavorable outcomes after aneurysmal SAH even though an
      association between APOE and incidence of the SAH may not exist. The effect of
      APOE on neurobiology and lipoprotein metabolism seems to partially explain the
      difference in outcomes and deserves further study.

PMID- 14572959
TI  - Roller coaster headaches revisited.
AB  - BACKGROUND: Roller coasters are probably one of the more popular rides at
      amusement parks around the world. Despite their relative safety, nontraumatic
      intracranial injuries have been reported following roller coaster rides. The
      presence of an intracranial arachnoid cyst may increase the risk of nontraumatic
      injury in this setting. CASE DESCRIPTION: We describe a 33-year-old female with a
      left middle fossa arachnoid cyst who presented with increasing headaches from
      bilateral subdural hygromas after a roller coaster ride. The patient underwent
      bilateral burr hole drainage of her subdural hygromas with resolution of her
      symptoms. CONCLUSION: This case demonstrates the potential risks of intracranial
      injury in patients with an underlying arachnoid cyst who engage in certain types
      of recreational activity.

PMID- 14572960
TI  - The conditional probabilities of survival in patients with anaplastic astrocytoma
      or glioblastoma multiforme.
AB  - BACKGROUND: By the use of conditional probabilities of survival, we studied the
      yearly survival rates for individual tumor survivors. METHODS: Conditional
      survival rate was estimated in 114 consecutive patients with anaplastic
      astrocytoma or glioblastoma multiforme. Conditional probabilities of surviving
      some years given survival to a specific period of time after craniotomy and 95%
      confidence intervals were calculated in the individual tumor survivors. RESULTS:
      The estimated median survival was 30 months for 45 patients with anaplastic
      astrocytoma and 12 months for 69 patients with glioblastoma multiforme. The
      conditional probabilities of surviving next one year given survival to 1 year, 2
      years, 3 years, 4 years, or 5 years after craniotomy for anaplastic astrocytoma
      were 86.2%, 75.0%, 85.9%, 77.8%, or 85.7%, respectively; for glioblastoma
      multiforme 64.8%, 58.7%, 85.7%, 80.0%, or 75.0%, respectively. The conditional
      probability of surviving to 5 years given survival to 2 years after craniotomy
      for anaplastic astrocytoma, i.e., surviving an additional 3 years, was 50.1%,
      which was better than observed 5-year survival rate (28.6%); for glioblastoma
      multiforme it was 40.2%, which also was better than observed 5-year survival rate
      (12.4%). CONCLUSIONS: The conditional probability of survival was a good method
      to clinically predict yearly survival rate for individual tumor survivors. In
      addition, the method can estimate the probabilities of surviving next some years
      given survival to a specific period of time after craniotomy. It also showed a
      more encouraging result than observed survival rate in patients with
      supratentorial malignant astrocytomas.

PMID- 14572962
TI  - Removal of ethmoidal malignant tumors by the isolated paralateronasal approach
      with resection of the cribriform plate and the dura mater.
AB  - OBJECTIVE: A series of ethmoidal tumors was resected by an entirely extracranial
      approach through a lateral rhinotomy incision, with partial maxillectomy and
      removal of the cribriform plate and dura mater from below. METHODS: Thirty-four
      consecutive patients (32 male, 2 female; mean age 64 years, range 45-78) with
      malignant tumors of the ethmoid sinus were operated by this technique between
      July 1998 and February 2002. All had complete tumor resection, including the
      cribriform plate and the dura mater. Excision was performed en bloc 23 times
      (68%). Although cerebral involvement was encountered in four cases (T4 IC), this
      technique was adequate for tumor resection, together with corticectomy when
      necessary. The method used for tumor resection and rebuilding of the anterior
      skull base is described in detail. RESULTS: There were no immediate postoperative
      deaths. One patient developed pneumococcal meningitis with cerebrospinal fluid
      leakage as a result of a technical error and required further surgery. Four
      patients presented a confusion syndrome that regressed during the hospital stay,
      2 complained of transient diplopia, and 4 had hematoma of the abdominal wall.
      Mean follow-up of 10.4 months (1-41 months) is still too short to reach
      definitive conclusions about oncologic results. CONCLUSIONS: This approach is
      particularly suitable for removal of tumors in contact with or invading the
      cribriform plate. Tumor resection is as extensive as with the traditional mixed
      approach, but does not require the frontal lobes to be drawn aside.

PMID- 14572964
TI  - Retrospective analysis of neurological outcome after intra-arterial thrombolysis
      in basilar artery occlusion.
AB  - BACKGROUND: Basilar artery occlusion usually has a very poor outcome and is
      associated with a high mortality rate. Local intra-arterial thrombolysis may
      improve the clinical outcome and reduce mortality in the treatment of acute
      basilar artery occlusion. We evaluated the possible variables affecting
      recanalization and clinical outcome in patients with basilar artery occlusions
      undergoing thrombolytic therapy. METHODS: We analyzed retrospectively the
      clinical course and outcome of a series of 26 patients between 1998 and 2001. All
      patients who were examined within 24 hours after onset of symptoms underwent
      emergency cerebral angiography and subsequent intra-arterial thrombolysis. Three
      patients additionally received percutaneous transluminal angioplasty of
      underlying stenosis at the site of thrombosis. RESULTS: Outcome was good in 9
      patients (34.6%) and poor in 17 (65.4%). Recanalization could be achieved in 24
      patients (92.3%) and was not affected by age, sex, site of occlusion, etiology,
      thrombolytic drugs, or time interval. Good outcome was associated with younger
      age, good initial clinical condition, and no evidence of brain stem infarction.
      There was no association between the interval (greater or less than 6 hours) from
      the onset of symptoms until the end of thrombolysis and survival. CONCLUSIONS: We
      confirm that intra-arterial thrombolysis reduces mortality in basilar artery
      occlusion. Young patients (<75 years) without any infarct in brain stem before
      the start of treatment seem to be the ideal candidates for thrombolysis. Basilar
      artery thrombosis could and should be reopened, even late (after 6 hours) after
      symptom onset.

PMID- 14572966
TI  - Dissecting aneurysm of the intracranial vertebral artery associated with proximal
      focal degeneration of the elastica: a comparative pathological study of the
      vertebral artery in patients with and without aneurysms.
AB  - BACKGROUND: The pathogenesis underlying intracranial dissecting aneurysms remains
      unclear. We performed a detailed study using vertebral artery specimens obtained
      at autopsy from patients with and without aneurysms to identify the primary
      abnormality resulting in weakness of the elastica. We compared our observations
      with those made in specimens manifesting the normal atherosclerotic process.
      METHODS: Using histologic methods, we examined intracranial vertebral artery
      specimens from two autopsied aneurysm patients and 13 autopsied control cases to
      compare the state of atherosclerosis and the weakness of the elastica at this
      aneurysm predilection site. RESULTS: Case 1: A 54-year-old woman with 2
      dissecting aneurysms of the bilateral vertebral arteries (VA) who died from
      recurrent subarachnoid hemorrhage (SAH). Case 2: A 53-year-old woman who died
      from SAH. Microscopically, all 3 vertebral aneurysms were typical transmural
      dissecting aneurysms. They manifested areas of focal, severe degeneration of the
      elastic lamina and calcification at VA sites proximal to the aneurysms. These
      lesions could be differentiated from secondary changes attributable to the
      aneurysms because of their separate location only proximal to the site of
      aneurysmal rupture. Atherosclerotic changes were minimal in both cases. In the
      controls, the degenerative state of the elastic lamina of the VA reflected an
      atherosclerotic process. CONCLUSIONS: We postulate that focal degeneration of
      elastic tissue not involved in the atherosclerotic process was the vasculopathy
      resulting in aneurysm formation in our SAH cases.

PMID- 14572969
TI  - Correlation of cephalic anthropometric parameters and microsurgical anatomy of
      the optic nerves: a cadaveric morphometric study.
AB  - BACKGROUND: This study was designed to elucidate the possible correlation of
      cranial anthropometric measurements with the chiasm to limbus sphenoidale
      distance to facilitate preoperative estimation of this distance and to choose a
      better surgical approach. METHODS: Thirty-three fresh adult cadaver heads (22
      males and 11 females) were evaluated for cranial anthropometric measurements. The
      precraniotomy anthropometric measurements included (A) inion to nasion distance
      and (B) the longest intermeatal meridian. Subsequently, with a standard
      craniotomy, the following intervals were measured: (C) optic chiasm to falciform
      ligament, (D) anterior aspect of optic chiasm to limbus sphenoidale, and (E)
      limbus sphenoidale to inner nasion. A combined ratio parameter, labeled as (F),
      was calculated from the following equation: F = B/E x 10. RESULTS: The mean
      values and standard errors of the mean of parameters A to F were 195.8 +/- 14.53
      mm, 374.7 +/- 25.29 mm, 10.47 +/- 1.89 mm, 9.93 +/- 2.01 mm, 38.46 +/- 3.17 mm,
      and 9.81 +/- 1.11, respectively. The parameter D had significant correlation to
      the parameters B, C, E, and F. The most significant correlation was seen between
      parameters D and F (p < 0.001). According to linear regression assessment between
      parameters D and F, the following regression equation was obtained: D = 4.24 +
      0.58F. CONCLUSIONS: Optic nerve topography and dimensions show inter-personal
      variations that may be anticipated to some extent with cranial anthropometric
      data. Calculating of F ratio gives us an acceptable estimation of the actual
      distance of chiasm to limbus sphenoidale, which in turn can help the surgeon to
      select the approach to tumors of intrasellar region. However, the role of
      meticulous imaging studies cannot be overemphasized to confirm the anticipated
      estimations.

PMID- 14572971
TI  - Oligodendroglioma and anaplastic oligodendroglioma: clinical features, treatment,
      and prognosis.
AB  - BACKGROUND: Recent advances that have been made in diagnostic imaging, surgical
      technique, chemotherapy, molecular biology, and prediction of therapeutic
      response could have potential impact on the optimal diagnosis and treatment of
      patients with brain tumors, especially those with oligodendrogliomas. In this
      article, the topic of oligodendroglioma and anaplastic oligodendroglioma is
      reviewed, highlighting the new clinical developments. METHODS: Information for
      this review was obtained by performing a Medline search for recent references
      using the term "oligodendroglioma." The bibliographies of papers obtained also
      were checked for articles that could provide additional understanding of this
      disease and its current treatment. RESULTS: The incidence of oligodendroglioma is
      increasing, most likely due to its improved recognition. Seizures and/or
      headaches are still common presenting features, and surgery continues to be the
      primary treatment. Positron emission tomography (PET) and molecular analysis of
      the surgical specimen are emerging as important diagnostic tools. Patients having
      either oligodendroglioma or anaplastic oligodendroglioma are likely to respond to
      chemotherapy. This has had an impact upon the timing of radiation therapy.
      Survival times are increasing, and patients can now be divided into prognostic
      subgroups based on the molecular features of their tumors. While procarbazine
      CCNU-vincristine (PCV) chemotherapy has been the standard, other agents, notably
      temozolomide, are currently being tested. CONCLUSIONS: The algorithm for
      diagnosing and treating patients with oligodendrogliomas has changed.
      Neurosurgeons need to be aware of the new developments so they can offer sound
      advice to their patients.

PMID- 14572972
TI  - Pterional craniotomy without keyhole to supratentorial cerebral aneurysms:
      technical note.
AB  - BACKGROUND: Patients who have pterional craniotomy occasionally complain of scalp
      deformity at the frontotemporal area because of craniotomy site. Especially, this
      occurs as a result of inappropriate repair of the bony defect at the keyhole with
      the complex curvature of the surrounding bone, although burr holes buttons are
      used. The author presents results of pterional craniotomy that is performed
      without keyhole to supratentorial cerebral aneurysms. METHODS: The temporal
      muscle was incised a few millimeters before its insertion at the superior
      temporal line, leaving a small fascial cuff for anatomic reattachment during
      closure. Only one burr hole was placed on the superior temporal line 3 to 4 cm
      posteriorly from the frontal base. After clipping of aneurysm, the bone flap was
      fixed using a titanium clamp (CranioFix) for a burr hole and 2 miniplates.
      RESULTS: Postoperative three-dimensional computerized tomography scans and
      photographs reveal excellent cosmetic results with the smooth cranial surface
      without scalp deformity at 6-month follow-up. Dural laceration developed in two
      cases, but there was no cerebral spinal fluid leakage after repair. CONCLUSION:
      Our technique offers good cosmetic results and less risk of disaster by
      intraoperative rupture of aneurysm than the keyhole surgery.

PMID- 14572975
TI  - Socialized medicine is the problem.

PMID- 14572974
TI  - Microsuture-tying forceps with attached scissors for bypass surgery.
AB  - BACKGROUND: Bypass surgery requires the shortest temporary occlusion time of a
      recipient artery during anastomosis. For this purpose, we have devised a
      microforceps with attached scissors that makes it possible to perform the
      multiple steps involved in anastomosis without exchanging instruments. This
      microforceps avoids having to exchange instruments twice in one suturing, such as
      that between a microsuture-tying forceps or a microneedle holder and
      microscissors in conventional methods. METHODS: The instrument is made of
      stainless steel and is 15.5 cm long. Using this microforceps with scissors, we
      can suture, tie, and cut a ligature fluently for consecutive sutures without
      exchanging instruments. The mean time during one suturing was compared between
      two patient groups treated by conventional method and with use of this
      instrument. RESULTS: This instrument was used for 34 patients with ischemic
      cerebrovascular disease (including three who needed deep-site anastomoses) and
      allowed us to perform superficial temporal artery-middle cerebral artery (STA
      MCA) anastomoses uneventfully. This instrument saved 15.2 s in the mean time
      during one suturing. CONCLUSIONS: Although it is of paramount importance to
      practice tying sutures well, this new instrument removes the need to exchange
      conventional instruments, and we believe it will save time and, therefore,
      decrease complications during bypass surgery.

PMID- 14572976
TI  - The death of spine surgery as we know it today.

PMID- 14572977
TI  - Percutaneous trigeminal ganglion balloon compression for treatment of trigeminal
      neuralgia--part I: pressure recordings.

PMID- 14573312
TI  - The corticotropin-releasing hormone binding protein is associated with major
      depression in a population from Northern Sweden.
AB  - BACKGROUND: Recent research suggests that central corticotropin releasing hormone
      hyperdrive is an important neurobiological risk factor for developing major
      depression. The availability of free corticotropin releasing hormone in the
      central nervous system is tightly regulated by the expression of corticotropin
      releasing hormone binding protein. Therefore, the gene encoding for corticotropin
      releasing hormone binding protein is a functional candidate gene for major
      depression. METHODS: We present a systematic study of single nucleotide
      polymorphisms in the corticotropin releasing hormone binding protein gene and
      their role in the liability for major depression. Seven single nucleotide
      polymorphisms were genotyped in a well-diagnosed sample of 89 patients with
      recurrent major depressions and matched controls. RESULTS: Two single nucleotide
      polymorphisms within the corticotropin releasing hormone binding protein gene
      were significantly associated with the disease (p <.05). An expectation
      maximization algorithm estimated a specific haplotype to have a frequency of 53%
      in patients and 35% in controls (p <.001). CONCLUSIONS: The corticotropin
      releasing hormone binding protein gene is likely to be involved in the genetic
      vulnerability for major depression.

PMID- 14573313
TI  - Stress hormone responses to corticotropin-releasing hormone in substance abusers
      without severe comorbid psychiatric disease.
AB  - BACKGROUND: Preclinical data indicate a crucial role of stress in the acute
      effects of drugs of abuse, maintenance of self-administration, and susceptibility
      to relapse. Stress system activation may serve as a marker for a neurochemical
      dysfunction with prognostic significance in patients with addiction. METHODS: We
      tested pituitary adrenocorticotrophin (ACTH) and adrenal cortisol response to
      ovine corticotropin-releasing hormone (oCRH) to assess the reactivity of the
      hypothalamic-pituitary-adrenal (HPA) axis in seven nonsubstance-abusing subjects,
      31 polysubstance-abusing subjects without depressive symptoms, and seven subjects
      with substance abuse and depressive symptoms. No subject met diagnostic criteria
      for depression or other severe psychiatric disease. RESULTS: Compared with normal
      control subjects, substance abusers showed significantly lower ACTH and cortisol
      responses over the course of oCRH stimulation (p <.0001). Substance abusers with
      depressive symptoms showed similarly blunted responses. CONCLUSIONS:
      Polysubstance abusers with no past or current diagnosis of other Axis I disorders
      show blunted ACTH and cortisol responses to oCRH administration. The finding of
      an activated HPA axis in this population suggests an overlapping role of central
      CRH and HPA axis activation in affective disorders and substance abuse, which is
      likely to constitute an endocrine milieu necessary for the maintenance of
      addictive behavior. These data support the role of future therapeutic trials with
      nonpeptide CRH receptor 1 antagonists in these patients.

PMID- 14573314
TI  - Serotonin transporter polymorphisms and adverse effects with fluoxetine
      treatment.
AB  - BACKGROUND: The short (S) allele of the serotonin transporter gene-linked
      polymorphic region (5HTTLPR) has been associated with poorer antidepressant
      response in major depressive disorder (MDD) and with antidepressant-induced
      mania. This study investigated a possible association with treatment-emergent
      insomnia or agitation. METHODS: Thirty-six outpatients with MDD were genotyped at
      5HTTLPR and treated with open-label fluoxetine up to 60 mg/day. Treatment
      emergent adverse effects were assessed at each study visit. RESULTS: Of nine
      subjects homozygous for the "S" allele, seven (78%) developed new or worsening
      insomnia, versus 6 of 27 (22%) non-"S"-homozygous subjects (Fisher's exact p
      =.005). Similarly, six of nine subjects homozygous for the "S" allele (67%)
      developed agitation, versus 2 of 27 (7%) of non-"S"-homozygous subjects (Fisher's
      exact p =.001). CONCLUSIONS: The "S" allele of the 5HTTLPR may identify patients
      at risk for developing insomnia or agitation with fluoxetine treatment. This
      preliminary result requires confirmation in larger samples.

PMID- 14573315
TI  - Serotonin transporter gene promoter (5-HTTLPR) and intron 2 (VNTR) polymorphisms
      in Croatian suicide victims.
AB  - BACKGROUND: Disturbances in serotonin (5HT) transmission are the most frequently
      reported neurobiological substrates of suicidal behavior. Because 5HT transporter
      plays a central role in the regulation of 5HT synaptic function and its gene
      contains two functional polymorphisms (5-HTTLPR in the promoter region and VNTR
      in the second intron), it represents an interesting candidate for association
      studies in suicidal behavior. METHODS: In this study, a possible association of 5
      HTTLPR and intron 2-VNTR polymorphisms of the 5HT transporter gene with suicidal
      behavior was investigated in a sample of 135 suicide victims and 299 healthy
      control subjects of Croatian/southern Slavic origin. RESULTS: There were no
      significant differences in 5-HTTLPR and intron 2-VNTR genotype- and allele-
      frequency distributions between suicide victims and healthy control subjects;
      however, a tendency toward an increase of 5-HTTLPR allele L and VNTR-allele 10
      were observed in suicide group. Analysis of distribution of estimated haplotype
      frequencies revealed differences between suicide victims and control subjects,
      with an excess of haplotype L10 among suicide victims (p =.0112). CONCLUSIONS:
      Our results provide modest evidence for a possible association of the 5HT
      transporter gene with a completed suicide. Further studies are needed to
      determine whether alterations in 5HTt gene expression are involved in suicidal
      behavior.

PMID- 14573316
TI  - Lack of effect of a single dose of hydrocortisone on serotonin(1A) receptors in
      recovered depressed patients measured by positron emission tomography with
      [11C]WAY-100635.
AB  - BACKGROUND: Elevated cortisol levels might account for the reduction in central
      serotonin 1A (5-hydroxytryptamine [5-HT](1A)) receptor binding and function
      observed in patients with major depression. We tested this hypothesis by studying
      the effect of acute administration of hydrocortisone on 5-HT(1A) receptor binding
      potential (BP) in subjects recovered from depression. METHODS: We studied 14
      subjects (8 male, 6 female) who had recovered from at least two episodes of major
      depression and had been euthymic and drug free for at least 6 months. Serotonin
      1A receptor BP was measured by [(11)C]WAY-100635 in conjunction with positron
      emission tomography. Subjects were tested on two occasions in a double-blind,
      random-order, crossover design after administration of either hydrocortisone (100
      mg orally) or placebo 12 hours previously. Positron emission tomography scans
      were analyzed with a region of interest analysis. RESULTS: Hydrocortisone
      treatment did not decrease 5-HT(1A) receptor BP either in the hippocampus, which
      was our a priori hypothesis, or in other cortical 5-HT(1A) regions; however,
      female subjects had a higher 5-HT(1A) receptor BP in certain brain areas compared
      with male subjects. CONCLUSIONS: These data are consistent with an earlier study
      in healthy volunteers and do not support the proposal that decreased 5-HT(1A)
      receptor BP in patients with acute major depression is a consequence of cortisol
      hypersecretion.

PMID- 14573317
TI  - Reduced left hemispheric white matter volume in twins with bipolar I disorder.
AB  - BACKGROUND: Although the heritability of bipolar I disorder (BPI) is high, few
      magnetic resonance imaging (MRI) studies of siblings of bipolar patients exist.
      We performed MRI brain scans on a nationwide sample of twins with BPI, as well as
      on their co-twins and a demographically balanced sample of control twin subjects,
      to detect any structural alterations related to the disorder and to the increased
      genetic risk. METHODS: The National Hospital Discharge Register, National
      Population Register, and Finnish Twin Cohorts were used to identify bipolar
      twins. Structured diagnostic interviews and MRI scans were obtained for 24 twins
      with BPI, 15 healthy co-twins, and 27 control twin subjects. RESULTS: Patients
      and co-twins showed a significant decrease in left hemispheric white matter
      volume. The disparity in patients was -16.1 cm(3) (95% confidence interval [CI] 
      26.6, -5.6) and in co-twins -11.3 cm(3) (95% CI -22.1, -0.4) compared with
      control twin subjects. No gray matter decrease was seen in patients or co-twins.
      CONCLUSIONS: The results of this first large-scale MRI study of twins with BPI,
      their co-twins, and appropriate control twin subjects, suggest that alterations
      of the left hemisphere white matter in BPI may reflect genetic factors
      predisposing to the disorder.

PMID- 14573318
TI  - Interferon-alpha-induced changes in tryptophan metabolism. relationship to
      depression and paroxetine treatment.
AB  - BACKGROUND: Tryptophan (TRP) degradation into kynurenine (KYN) by the enzyme,
      indoleamine-2,3-dioxygenase, during immune activation may contribute to
      development of depressive symptoms during interferon (IFN)-alpha therapy.
      METHODS: Twenty-six patients with malignant melanoma were randomly assigned in
      double-blind fashion to receive either placebo or paroxetine, beginning 2 weeks
      before IFN-alpha treatment and continuing for the first 12 weeks of IFN-alpha
      therapy. At treatment initiation and at 2, 4, and 12 weeks of IFN-alpha
      treatment, measurements of TRP, KYN, and neopterin (a marker of immune
      activation), were obtained, along with structured assessments of depression,
      anxiety, and neurotoxicity. RESULTS: Regardless of antidepressant treatment
      status, all patients exhibited significant increases in KYN, neopterin, and the
      KYN/TRP ratio during IFN-alpha therapy. Among antidepressant-free patients,
      patients who developed major depression exhibited significantly greater increases
      in KYN and neopterin concentrations and more prolonged decreases in TRP
      concentrations than did nondepressed, antidepressant-free patients. Moreover, in
      antidepressant-free patients, decreases in TRP correlated with depressive,
      anxious, and cognitive symptoms, but not neurovegetative or somatic symptoms. No
      correlations were found between clinical and biological variables in
      antidepressant-treated patients. CONCLUSIONS: The results suggest that reduced
      TRP availability plays a role in IFN-alpha-induced depressive symptoms, and
      paroxetine, although not altering the KYN or neopterin response to IFN-alpha,
      attenuates the behavioral consequences of IFN-alpha-mediated TRP depletion.

PMID- 14573319
TI  - Disulfiram facilitates the development and expression of locomotor sensitization
      to cocaine in rats.
AB  - BACKGROUND: Disulfiram (DS; Antabuse) inhibits dopamine-beta-hydroxylase leading
      to increased brain dopamine levels and shows treatment efficacy for cocaine
      addiction. Yet few preclinical studies have been performed. This study
      establishes the effects of DS on locomotor sensitization to cocaine in rats.
      METHODS: Rats were administered vehicle, cocaine (10 mg/kg; intraperitoneally
      [IP]), or DS (50 or 100 mg/kg; IP) alone or in combination for 5 days
      (development phase). Locomotor activity was measured for 60-min each day. After a
      10-day drug washout, rats were administered cocaine, and locomotor activity was
      measured (expression phase). Plasma cocaine levels were assessed in separate
      groups of rats administered one of two cocaine doses (0 or 10 mg/kg) and one of
      two DS doses (0 or 100 mg/kg) for 5 days. Ten days later, blood was collected 60
      min postcocaine injection. RESULTS: The development of cocaine locomotor
      sensitization was facilitated by DS even though DS alone had minimal effect on
      activity levels. Furthermore, expression of sensitization was greatest in rats
      previously administered DS, an effect that cannot be attributed to altered plasma
      cocaine levels. CONCLUSIONS: Because DS shows treatment efficacy for cocaine
      addiction, results from this study suggest potential treatment agents should
      enhance, not attenuate, locomotor sensitization in rats.

PMID- 14573320
TI  - Polymorphisms in the N-methyl-D-aspartate receptor 1 and 2B subunits are
      associated with alcoholism-related traits.
AB  - BACKGROUND: This study examined the hypothesis that allelic variants of the
      ionotropic glutamatergic N-methyl-D-aspartate receptor (NMDAR) are associated
      with vulnerability to alcoholism and some related traits. METHODS: We
      investigated the silent G2108A and C2664T polymorphisms of the NMDAR1 and the
      NMDAR2B genes, respectively. The case control study included 367 alcoholic and
      335 control subjects of German origin. The family-based study comprised 81 Polish
      alcoholic patients and their parents using the transmission disequilibrium test.
      RESULTS: The genotype frequencies of the NMDAR1 polymorphism differed
      significantly between control and alcoholic subjects. This difference was also
      observed in more homogenous subgroups of alcoholic subjects with vegetative
      withdrawal syndrome and Cloninger type 1. Patients with a history of delirium
      tremens or seizures during withdrawal showed a significantly increased prevalence
      of the A allele. Genotyping of the NMDAR2B polymorphism revealed a significantly
      reduced T allele in Cloninger type 2 alcoholics and in patients reporting an
      early onset compared with control subjects. Our family-based study for NMDAR2B,
      revealed a trend to a preferred transmission of the C allele by the fathers, and
      families with early-onset patients contributed most to this trend. CONCLUSIONS:
      These results suggest that variants in NMDAR genes are associated with alcoholism
      and related traits.

PMID- 14573321
TI  - A disturbance of gastric function in bulimia nervosa.
AB  - BACKGROUND: Because the stomach plays an important role in the development of
      satiety, gastric function was examined in bulimia nervosa (BN). METHODS: Sixteen
      patients with BN and 16 controls swallowed an inflatable bag, which was
      positioned in the proximal stomach. Minimal distending pressure (MDP), the
      pressure needed to overcome intraabdominal pressure, was determined. Gastric
      volume was recorded after subjects drank a liquid meal. RESULTS: MDP was similar
      in patient and control groups (7.56 +/- 2.13 vs. 7.13 +/- 2.06 mmHg; t =.57, df =
      30, p =.58). Average postmeal gastric relaxation was significantly lower in the
      patient group (29.7 +/- 97.8 vs. 105.1 +/- 103.3 mL; t = 2.13, df = 30, p =.042).
      CONCLUSIONS: Stomach relaxation following food consumption is significantly
      diminished in patients with BN. Physiologic abnormalities of stomach function in
      BN may contribute to the perpetuation of disturbances in behavior in this
      disorder.

PMID- 14573322
TI  - Recovery and chronicity in anorexia nervosa: brain activity associated with
      differential outcomes.
AB  - BACKGROUND: The course of anorexia nervosa varies from rapid recovery to a
      chronic debilitating illness. This study aimed to identify functional neural
      correlates associated with differential outcomes. METHODS: Brain reactions to
      food and emotional visual stimuli were measured with functional magnetic
      resonance imaging in nine women who had long-term recovery from restricting
      anorexia nervosa. These were compared with age- and education-matched groups of
      eight women chronically ill with restricting anorexia nervosa and nine healthy
      control women. RESULTS: In response to food stimuli, increased medial prefrontal
      and anterior cingulate activation, as well as a lack of activity in the inferior
      parietal lobule, differentiated the recovered group from the healthy control
      subjects. Increased activation of the right lateral prefrontal, apical
      prefrontal, and dorsal anterior cingulate cortices differentiated these recovered
      subjects from chronically ill patients. Group differences were specific to food
      stimuli, whereas processing of emotional stimuli did not differ between groups.
      CONCLUSIONS: Separate neural correlates underlie trait and state characteristics
      of anorexia nervosa. The medial prefrontal response to disease-specific stimuli
      may be related to trait vulnerability. Lateral and apical prefrontal involvement
      is associated with a good outcome.

PMID- 14573323
TI  - Androgen receptor CAG repeat polymorphism is associated with cognitive function
      in older men.
AB  - BACKGROUND: Androgen receptors are located throughout the brain, especially in
      regions involved with learning and memory. Different lengths of a CAG (glutamine)
      repeat polymorphism in exon 1 of the androgen receptor gene may influence
      androgen action, with longer repeat lengths conferring decreased androgen
      sensitivity. METHODS: We sought to determine if this CAG polymorphism was
      associated with cognition in older men. RESULTS: Among 301 community-dwelling
      white men (mean age, 73.0 +/- 7.1), greater CAG repeat length was associated with
      lower scores on three cognitive tests (p <.05 for all). In addition, 12
      participants (9.8%) had cognitive impairment in the low tertile of CAG repeat
      length whereas 29 (16.3%) had cognitive impairment in the two higher tertiles
      (odds ratio = 1.8; 95% confidence interval =.9-3.7). CONCLUSIONS: Research should
      be directed at identifying the mechanism for this association and to determine if
      treatment with testosterone prevents cognitive decline.

PMID- 14573324
TI  - Immediate treatment with propranolol decreases posttraumatic stress disorder two
      months after trauma.
AB  - BACKGROUND: This study investigated the efficacy of propranolol prescribed
      shortly after trauma exposure in the prevention of posttraumatic stress disorder
      (PTSD) symptoms and diagnosis. METHODS: Eleven patients received 40 mg of
      propranolol 3 times daily for 7 days, followed by a taper period of 8-12 days.
      They were compared with eight patients who refused propranolol but agreed to
      participate in the study. Though nonrandomized, the two groups did not differ on
      demographics, exposure characteristics, physical injury severity, or
      peritraumatic emotional responses. RESULTS: Posttraumatic stress disorder rates
      were higher in the group who refused propranolol (3/8) compared with those who
      received the medication (1/11), as were the levels of PTSD symptoms (U = 85, p
      =.037). CONCLUSIONS: Our results are consistent with earlier findings and suggest
      that propranolol may be useful for mitigating PTSD symptoms or perhaps even
      preventing the development of PTSD.

PMID- 14573325
TI  - Changes in cardiovascular risk by reduction of left ventricular mass in
      hypertension: a meta-analysis.
AB  - BACKGROUND: Some studies have suggested that serial changes in left ventricular
      (LV) mass in hypertensive subjects predict the subsequent risk of cardiovascular
      disease. The aim of this meta-analysis was to evaluate the prognostic impact of
      LV hypertrophy regression in hypertension. METHODS: We undertook a meta-analysis
      of studies that reported echocardiographic LV mass before and during
      antihypertensive therapy, with subsequent assessment of cardiovascular events.
      The aims of this meta-analysis were: 1) to compare subjects with LV hypertrophy
      (LVH) during treatment (persistence or new development of LVH) with those with
      LVH at baseline, but not during treatment (regression of LVH); and 2) to compare
      subjects with LVH at baseline, but not during treatment with those without LVH
      both before and during treatment (regression of LVH versus persistently normal LV
      mass). RESULTS: The four eligible studies included 1064 hypertensive subjects
      (41% women) aged 45 to 51 years who repeated the echocardiographic study 3 to 10
      years after the initial examination. The definition of LVH was based on a LV mass
      corrected by body surface area >125 g/m(2) in two studies and >110 g/m(2) (for
      women) and 124 g/m(2) (for men) in two studies. Compared with subjects with lack
      of regression or new development of LVH, those with LVH regression showed a
      reduced risk of subsequent cardiovascular disease (odds ratio 0.41, 95% CI 0.21
      to 0.78, P =.007). Compared with subjects with regression of LVH, those with
      persistently normal LV mass showed a similar risk of subsequent events (odds
      ratio 0.64, 95% CI = 0.31 to 1.30, P =.21). CONCLUSION: Compared with persistence
      or new development of LV hypertrophy, regression of LV hypertrophy during
      antihypertensive treatment is associated with a marked reduction in risk for
      subsequent cardiovascular disease.

PMID- 14573326
TI  - Blunted nocturnal fall in blood pressure and left ventricular mass in elderly
      individuals with recently diagnosed isolated systolic hypertension.
AB  - BACKGROUND: Few studies have investigated the relationship between the lack of or
      reduction of nocturnal blood pressure (BP) fall and left ventricular mass (LVM)
      in elderly individuals with isolated systolic hypertension (ISH), notwithstanding
      the fact that ISH is the most frequent subtype of uncontrolled hypertension and a
      powerful risk factor for organ damage. The aim of this study was to identify the
      relationship between blunted nocturnal BP fall and LVM in elderly individuals
      with ISH that was recently diagnosed (within 2 years) and had never been treated.
      METHODS: A total of 64 elderly patients with recent ISH were recruited among the
      outpatients of the Hypertension Unit at 1st Institute of Medicine of "La
      Sapienza" University in Rome, and they underwent 24-h ambulatory BP monitoring
      (ABPM). According to exclusion criteria, 37 patients were selected for the study.
      Based on the presence or absence of an almost 10% reduction in systolic BP (SBP)
      and diastolic BP (DBP) from day to night, 21 so-called dippers and 16 nondippers,
      respectively, were identified. All of these 37 patients underwent
      echocardiography. Relationships between BP recordings and echocardiographic
      parameters were assessed by univariate analysis. Dippers and nondippers were
      compared with respect to LVM. RESULTS: Nighttime SBP was closely associated with
      indexed LVM (LVM/h(2.7)) (r = 0.564; P=.001). Nondippers showed significantly
      higher LVM/h(2.7) compared with dippers (62.43 +/- 15.39 g/m(2.7) v 51.33 +/-
      12.68 g/m(2.7) respectively; P=.021). CONCLUSIONS: An association between blunted
      nocturnal SBP fall and increased LVM was observed in the early phases of ISH in
      the elderly. This finding may have important prognostic implications.

PMID- 14573327
TI  - Hypertension care and control in underserved urban African American men:
      behavioral and physiologic outcomes at 36 months.
AB  - BACKGROUND: African American men with hypertension in low socioeconomic urban
      populations achieve poor rates of hypertension control and suffer early from its
      complications. METHODS: In a randomized clinical trial with 309 hypertensive
      urban African American men aged 21 to 54 years, we evaluated the effectiveness of
      a more intensive comprehensive educational-behavioral-pharmacologic intervention
      by a nurse practitioner-community health worker-physician (NP/CHW/MD) team and a
      less intensive education and referral intervention in controlling blood pressure
      (BP) and minimizing progression of left ventricular hypertrophy (LVH) and renal
      insufficiency. Changes in BP, left ventricular mass (LVM), and serum creatinine
      from baseline to 36 months were compared between groups. RESULTS: At 36 months,
      the mean systolic BP/diastolic BP change from baseline was -7.5/-10.1 mm Hg for
      the more intensive group and +3.4/-3.7 mm Hg for the less intensive group (P
      =.001 and.005 for between-group differences in systolic BP and diastolic BP,
      respectively). The proportion of men with controlled BP (<140/90 mm Hg) was 44%
      in the more intensive group and 31% in the less intensive group (P =.045). The
      LVM was significantly lower in the more intensive group than in the less
      intensive group (more intensive, 274 g; less intensive, 311 g; P =.004). There
      was a trend toward slowing of the progression of renal insufficiency (incidence
      of 50% increase in serum creatinine) in the more intensive group compared to the
      less intensive group (more intensive, 5.2%; less intensive, 8.0%; P =.08).
      CONCLUSIONS: During 36 months, the more intensive intervention led to a lower BP
      and decreased progression of LVH in a sample of hypertensive young African
      American men.

PMID- 14573328
TI  - Carotid sinus stimulation responses are related with arterial elastic properties
      in hypertensive subjects.
AB  - BACKGROUND: Exaggerated carotid sinus stimulation (CSStim) responses are
      associated with advancing age, hypertension, and atherosclerotic disease.
      However, there is little information regarding the contribution of the functional
      arterial status in the degree of CSStim responses at the very early stages of the
      hypertensive disease. METHODS: Carotid sinus stimulation (with simultaneous
      recordings of the electrocardiogram (ECG) and the blood pressure [BP] at the
      brachial artery) was performed in 90 newly diagnosed patients with stage I to II
      essential hypertension (aged 54 +/- 10 years; office BP, 154/97 mm Hg) and in 75
      normotensive controls matched for age and sex. The cardioinhibitory type of
      CSStim responses was evaluated by calculating an index defined as the ratio of
      the longest R-R interval on the ECG recording during stimulation to R-R interval
      at rest. Common carotid artery (CCA) distensibility was calculated as a function
      of changes in diameter (determined by echocardiography) and pulse pressure
      (determined sphygmomanometrically at the brachial artery). RESULTS: The two
      groups did not differ regarding the demographic and laboratory data. Hypertensive
      subjects compared to controls had decreased CCA distensibility (1.18 v 1.64 dyne(
      1) cm(2) 10(-6), P <.005) and increased CSStim responses index (1.74 +/- 1.03 v
      1.37 +/- 0.99, P <.001). By using a multivariate model including age, office
      pulse pressure, left ventricular mass index, and CCA distensibility, it was
      revealed that only CCA distensibility was a significant determinant of CSStim
      responses index (P <.005). CONCLUSIONS: Hypertension-induced alterations in CCA
      elastic properties accompany changes in CSStim responses. These findings may
      contribute to the understanding of the mechanisms between atherosclerotic disease
      and CSStim responses.

PMID- 14573329
TI  - Acute caffeine intake influences central more than peripheral blood pressure in
      young adults.
AB  - BACKGROUND: The aim of this study was to characterize the acute effects of
      caffeine on peripheral and central blood pressure (BP) in healthy individuals,
      using validated noninvasive techniques. METHODS: In a randomized double-blind
      study, 300 mg caffeine or matching placebo was administered orally to 20 healthy
      adults and hemodynamic responses were observed. Central BP and augmentation index
      (AIx) were determined by pulse wave analysis; cardiac index (CI) was estimated by
      transthoracic bioimpedance; and heart rate variability (HRV) given by power
      spectral analysis of pulse interval. Pressure amplification (peripheral to
      central pulse pressure ratio) and systemic vascular resistance index were also
      calculated. RESULTS: Caffeine administration increased central systolic and
      diastolic BP by 7 +/- 3 (P <.01) and 3 +/- 2 mm Hg (P <.05), respectively (mean
      +/- SEM) at 45 min, but had no effect on peripheral BP. Caffeine caused AIx to
      increase by 7 +/- 2 and 0 +/- 1%, respectively (P <.05), and pressure
      amplification to decrease by 1.0 +/- 0.1 v 0.2 +/- 0.2 (P <.001) placebo at 45
      min. CONCLUSIONS: Acute caffeine intake significantly increases central BP and
      large artery waveform transmission and diminishes pressure amplification in
      healthy adults. Therefore, the effects of caffeine on BP may be significantly
      underestimated by measurement of BP at the brachial artery.

PMID- 14573330
TI  - Efficacy of low-dose spironolactone in subjects with resistant hypertension.
AB  - BACKGROUND: Previous reports have demonstrated the antihypertensive efficacy of
      high doses of spironolactone in subjects with primary aldosteronism and, to a
      lesser degree, subjects with resistant hypertension. METHODS: In current
      analysis, we examined the antihypertensive benefit of adding low-dose
      spironolactone to multidrug regimens that included a diuretic and an angiotensin
      converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) in
      subjects with resistant hypertension with and without primary aldosteronism.
      Subjects referred for resistant hypertension were evaluated with an early morning
      plasma renin activity, 24-h urinary aldosterone and sodium during a high dietary
      salt ingestion. The diagnosis of primary aldosteronism was confirmed with a renin
      activity <1.0 ng/mL/h, urinary aldosterone >12 mug/24 h and urinary sodium >200
      mEq/24 h. After biochemical evaluation, spironolactone (12.5 to 25 mg/d) was
      added to each subject's antihypertensive regimen. If blood pressure (BP) remained
      uncontrolled, the dose of spironolactone was titrated up to 50 mg/d. Follow-up BP
      was determined at 6 weeks, 3 months, and 6 months. RESULTS: A total number of 76
      subjects were included in the analysis, 34 of whom had biochemical primary
      aldosteronism. Low-dose spironolactone was associated with an additional mean
      decrease in BP of 21 +/- 21/10 +/- 14 mm Hg at 6 weeks and 25 +/- 20/12 +/- 12 mm
      Hg at 6-month follow-up. The BP reduction was similar in subjects with and
      without primary aldosteronism and was additive to the use of ACE inhibitors,
      ARBs, and diuretics. CONCLUSIONS: We conclude that low-dose spironolactone
      provides significant additive BP reduction in African American and white subjects
      with resistant hypertension with and without primary aldosteronism.

PMID- 14573331
TI  - Effect of dual angiotensin converting enzyme/neutral endopeptidase inhibition,
      angiotensin converting enzyme inhibition, or AT1 antagonism on coronary
      microvasculature in spontaneously hypertensive rats.
AB  - Microvascular remodeling contributes to increased cardiovascular risk in
      hypertension. The dual angiotensin converting enzyme (ACE) and neutral
      endopeptidase (NEP) inhibitor omapatrilat improves small artery remodeling in
      hypertension. The aim of the present study was to compare effects of omapatrilat
      to the ACE inhibitor fosinopril and the AT(1) antagonist irbesartan on the
      coronary microvasculature in spontaneously hypertensive rats (SHR). Ten-week-old
      SHR were treated for 10 weeks with omapatrilat (20 or 40 mg/kg/d), irbesartan (50
      mg/kg/d), or fosinopril (20 mg/kg/d). Arterioles and capillaries were identified
      in the myocardium by immunolabeling. After 10 weeks, systolic blood pressure (BP)
      was significantly reduced in treated versus untreated SHR (P <.01). Myocardial
      arteriolar density/mm(2) was higher (P <.05) in untreated SHR versus Wistar-Kyoto
      (WKY), and was reduced by omapatrilat (at both high and low doses) and by
      fosinopril (P <.01). Irbesartan decreased only subepicardial arteriolar density
      (P <.05). Myocardial capillary density/mm(2) was decreased in untreated SHR
      versus WKY (P <.01), associated with increase in cardiomyocyte cross-sectional
      area and cardiomyocyte-to-capillary ratio, and a decrease in myocyte density.
      Omapatrilat (at both high and low doses) resulted in increased capillary density,
      decreased myocyte hypertrophy and cardiomyocyte to capillary ratio, and increased
      myocyte density (P <.01). Fosinopril and irbesartan reduced myocyte hypertrophy
      of SHR, but had no effect on capillary density. Dual ACE/NEP inhibition was more
      effective than ACE inhibition or AT(1) antagonism in improving microvascular and
      cardiomyocyte remodeling in the hypertensive heart. This suggests a role for NEP
      inhibition added to blockade of the renin-angiotensin system that may explain the
      greater efficacy of omapatrilat.

PMID- 14573332
TI  - Influence of low high-density lipoprotein cholesterol on left ventricular
      hypertrophy and diastolic function in essential hypertension.
AB  - BACKGROUND: Left ventricular (LV) hypertrophy and LV diastolic dysfunction, which
      are common cardiac changes in hypertensive patients, are modified by several
      nonhemodynamic (eg, genetic, neurohumoral, and metabolic) factors. However, the
      influence of serum lipids on these LV changes has not been sufficiently studied.
      Although low high-density lipoprotein (HDL) cholesterol is well known to be a
      major risk factor for coronary heart disease, it is unclear whether HDL
      cholesterol plays a role in hypertensive heart disease. METHODS: In 274 patients
      with treated essential hypertension, two-dimensional and Doppler echocardiography
      were performed, and LV mass, ratio of peak velocity of atrial filling to early
      diastolic filling (A to E ratio [A/E]), and deceleration time of the E-wave were
      evaluated. The relationship of dyslipidemia, especially low HDL cholesterol, to
      LV hypertrophy and diastolic function was investigated in these patients.
      RESULTS: In a univariate regression analysis, HDL cholesterol was inversely
      associated with LV mass, A/E, and deceleration time. The association of HDL
      cholesterol with LV diastolic function was observed in both men and women. Its
      association with LV mass was gender-dependent, being significant only in women.
      Triglycerides were weakly correlated with LV mass and A/E, but total and low
      density lipoprotein cholesterol had no correlations with these indices. In a
      multiple regression analysis, only low HDL cholesterol among several lipid levels
      was an independent predictor of both LV mass and LV diastolic dysfunction.
      CONCLUSIONS: Our findings suggest that low HDL cholesterol may unfavorably modify
      LV structure and diastolic function in patients with treated essential
      hypertension.

PMID- 14573333
TI  - The Arg16Gly polymorphism of the beta2-adrenergic receptor and left ventricular
      systolic function.
AB  - BACKGROUND: beta-Adrenergic receptors (ARs), including beta1- and beta2-AR, are
      involved in modulation of cardiac contractility and heart rate. Arg16Gly, a
      functional polymorphism in the beta2-AR gene, has been reported to influence
      exercise capacity in heart failure patients. This study examined the association
      of the beta2-AR Arg16Gly polymorphism with left ventricular (LV) systolic
      function in a biethnic population-based sample. METHODS: Echocardiograms and the
      beta2-AR Arg16Gly polymorphism were analyzed in 267 normotensive (54% African
      Americans) and 252 severe hypertensive (53% African Americans) adults without
      coronary heart disease or diabetes. RESULTS: The frequencies of Gly16Gly16,
      Arg16Gly16, and Arg16Arg16 were 28.1%, 54.3%, and 17.6%, respectively, in
      normotensives, and 31.4%, 47.6%, and 21.0%, respectively, in hypertensives. In
      normotensives, the Gly16Gly16 homozygotes displayed greater fractional shortening
      (35.9% +/- 4.3% v 34.1% +/- 4.7% v 34.0% +/- 3.9%, P =.01), ejection fraction
      (65.0% +/- 5.8% v 62.5% +/- 6.4% v 62.6% +/- 5.4%, P =.01), midwall shortening
      (18.6% +/- 1.6% v 17.9% +/- 1.9% v 18.0% +/- 1.6%, P =.02), and stress-corrected
      midwall shortening (110.1% +/- 9.3% v 106.1% +/- 10.6% v 108.1% +/- 10.8%, P
      =.03) compared to the Arg16Gly16 and Arg16Arg16 groups. These associations were
      independent of age, sex, ethnicity, heart rate, body mass index, systolic blood
      pressure, LV end-diastolic dimension, and field center. No significant
      associations between the beta2-AR Arg16Gly polymorphism and echocardiographic
      measures were found in hypertensives. CONCLUSIONS: The Arg16Gly polymorphism of
      beta2-AR may be a marker for LV chamber function and contractility in
      normotensive adults.

PMID- 14573334
TI  - Association between microalbuminuria and the metabolic syndrome: NHANES III.
AB  - We investigated whether microalbuminuria was associated with the metabolic
      syndrome by comparing the strength of the association between microalbuminuria
      and the syndrome as a whole and its individual components. This investigation
      included 5659 women and men aged 20 to 80 years from the cross-sectional,
      nationally representative, Third National Health and Nutrition Examination Survey
      (NHANES III: 1988-1994). Metabolic syndrome was defined as any three of the
      following: increased waist circumference, increased triglycerides, decreased HDL
      cholesterol, increased blood pressure, or high fasting glucose. Microalbuminuria
      was defined as urinary albumin/creatinine ratio of 30 to 300 mg/g.
      Microalbuminuria was present in 7.8% of women and 5.0% of men. Log linear
      analysis revealed a significant association between the metabolic syndrome and
      microalbuminuria in both genders (women chi(2) = 44.1; men chi(2) = 59.6; P
      <.0001 for both). Microalbuminuria was more common in both women (odds ratio [OR]
      = 2.2; 95% confidence interval [CI] 1.44, 3.34) and men (OR = 4.1; 95% CI 2.45,
      6.74) with metabolic syndrome compared to those without it; 34% of women and 42%
      of men with microalbuminuria also had metabolic syndrome. After adjusting for
      other components of the metabolic syndrome, hypertension demonstrated the
      strongest association with microalbuminuria in both women (OR = 3.34; 95% CI
      2.45, 4.55) and men (OR = 2.51; 95% CI 1.63, 3.86). Microalbuminuria and
      metabolic syndrome are associated in a large, nationally representative cohort,
      possibly due to early renal effects of hypertension, and it may be useful to
      consider microalbuminuria as a component of the metabolic syndrome.

PMID- 14573335
TI  - Long-term effects of intensive blood-pressure lowering on arterial wall stiffness
      in hypertensive patients.
AB  - BACKGROUND: Aortic stiffness is assessed by pulse wave velocity (PWV) and
      predicts the cardiovascular morbidity and mortality of hypertensive patients. To
      determine the long-term effects of intensive blood pressure (BP) lowering by
      antihypertensive drug therapy on aortic stiffness assessed by PWV, a single-blind
      randomized prospective study was performed. METHODS: One hundred forty
      nondiabetic hypertensive patients (67.6 +/- 0.9 years old; systolic/diastolic BP:
      177 +/- 1/101 +/- 1 mm Hg) were assigned to an intensive control group (IC) with
      a target BP of <130/85 mm Hg (n = 71) or a moderate control group (MC) with a
      target BP of <140/90 mm Hg (n = 69), and aortic stiffness was assessed every 3
      months by measuring aortic PWV with a pulse pressure analyzer. RESULTS: During
      the 12-month treatment period, BP significantly decreased to 129 +/- 1/78 +/- 1
      mm Hg and 152 +/- 2/87 +/- 1 mm Hg in the IC and MC, respectively. At the
      beginning of the study, PWV in the IC and MC was similar, averaging 1779 +/- 41
      and 1885 +/- 50 cm/sec, respectively. By the end of the treatment period,
      however, PWV had decreased to 1621 +/- 34 cm/sec in the IC, but had not changed
      significantly in the MC. In the IC, the ratio of the change in PWV to the change
      in BP increased with the duration of BP lowering. Clinical and biological
      parameters were similar in both groups, except that higher doses of amlodipine
      were used in the IC. CONCLUSIONS: Long-term intensive BP lowering in the
      hypertensive patients was associated with a significant reduction in aortic
      stiffness distinct from its acute depressor effect.

PMID- 14573336
TI  - Effects of exercise and beta-blocker on blood pressure and baroreflexes in
      spontaneously hypertensive rats.
AB  - BACKGROUND: Exercise training or beta-blocker decreases high blood pressure (BP)
      and improves abnormal baroreflex function associated with hypertension. This
      study was undertaken to examine whether the effects of exercise training are
      additive to beta-blocker in spontaneously hypertensive rats (SHR). METHODS: At 5
      weeks of age, SHR were allocated to four groups: sedentary control, exercise
      training, treatment with moderate dose of bisoprolol, and their combination.
      Systolic BP was monitored by the tail-cuff method under restrained conditions.
      Sigmoidal mean arterial pressure (MAP)-heart rate (HR) reflex curves were
      obtained in rats at 17 weeks of age under quiet conditions before and after
      atenolol to ensure sympathetic blockade and to determine the vagal component of
      gain. After studying baroreflex function, intrinsic HR was obtained by additional
      administration of atropine. RESULTS: Before atenolol, both exercise training
      alone and bisoprolol alone lowered resting MAP and HR, and decreased upper
      plateau (maximal tachycardia) and lower plateau (maximal bradycardia), resulting
      in decreased sympathetic component of HR range (upper plateau - intrinsic HR) and
      increased vagal component of HR range (intrinsic HR - lower plateau). After
      atenolol, both exercise training alone and bisoprolol alone increased the gain of
      vagal component. Exercise training had no additive effect on any parameters to
      bisoprolol except for systolic BP and HR measured by the tail-cuff method.
      CONCLUSIONS: Exercise training and bisoprolol have similar effects concerning
      resting hemodynamics and baroreflex function in SHR. Although additive effects of
      exercise training to bisoprolol are not evident under quiet, nonstressful
      conditions, some additive effects may be obtained under stress such as restrain.

PMID- 14573337
TI  - Cellular mechanisms of insulin resistance in rats with fructose-induced
      hypertension.
AB  - BACKGROUND: Feeding a high-fructose diet induces hypertension and insulin
      resistance in Sprague-Dawley rats. METHODS: To investigate whether insulin
      receptors contribute to abnormal glucose metabolism and whether their regulation
      is differentially regulated in different tissues, we evaluated the glycemic and
      insulinemic response to an oral glucose load, insulin receptor binding, and
      insulin receptor messengerRNA (mRNA) levels in tissues of rats that were fed
      either standard rat chow or a diet containing 66% fructose for 2 weeks. RESULTS:
      Blood pressure and plasma triglycerides increased significantly in the fructose
      fed rats, whereas body weight, fasting plasma glucose, and plasma insulin did not
      differ significantly from controls. Plasma glucose and insulin responses to oral
      glucose were significantly greater in fructose-fed than in control rats. Insulin
      receptor-binding characteristics were determined by an in situ autoradiographic
      technique associated with computerized microdensitometry. The insulin receptor
      number was significantly lower in both skeletal muscle and liver of fructose-fed
      rats as compared to controls, whereas no difference was observed in the kidney.
      No significant differences were found in binding affinity. Insulin receptor mRNA
      levels were determined by slot-blot hybridization with a cRNA probe encoding the
      5' end of the rat insulin receptor cDNA. Consistent with binding data, mRNA
      levels were significantly lower in skeletal muscle and liver of fructose-fed rats
      as compared to controls, but not in the kidney. CONCLUSIONS: Decreased number of
      insulin receptors occurring at the level of gene expression is present in
      skeletal muscle and liver of fructose-fed rats and might contribute to insulin
      resistance in this model.

PMID- 14573338
TI  - Role of systolic blood pressureon the progression of kidney damage in an
      experimental model of type 2 diabetes mellitus, obesity, and hypertension (Zucker
      rats).
AB  - BACKGROUND: Hypertension is the main risk factor for the progression of kidney
      damage in diabetes mellitus. The aim of the present work is to compare the effect
      of the treatment with irbesartan (IRBE) and omapatrilat (OMA), in obese Zucker
      rats (OZR). METHODS: A group of 45 OZR were uninephrectomized to accelerate renal
      damage, and divided into three groups: two experimental groups (IRBE and OMA)
      treated with 50 and 40 mg/kg/d, respectively; and the control group (CG). At the
      end of the 8-month follow-up period, animals were killed and the remnant kidney
      was removed for histologic study and to evaluate the transforming growth factor
      beta1 (TGF-beta1) expression. RESULTS: Both therapies reduced blood pressure (BP)
      versus CG (P <.001). Moreover, systolic BP was significantly lower in the OMA
      group than in the IRBE group (P <.001). Also, both treatments significantly
      lowered the urinary albumin excretion (P <.001). The OMA treatment exhibited
      lower values than the IRBE treatment (P <.05). The kidney TGF-beta1 expression
      was reduced by both treatments to a similar level. The correlation between
      systolic BP and glomerulosclerosis (GS) is very high (r = 0.90; P <.0001). Also,
      a high correlation was observed between GS and proteinuria (r = 0.79, P <.0001).
      The correlation between systolic BP and proteinuria was weaker (r = 0.69; P
      <.01). CONCLUSIONS: These data suggest that both therapies are effective in
      ameliorating the progression of renal damage in this experimental model.
      Omapatrilat affords greater long-term renoprotection than irbesartan, mainly due
      to its potent effect in reducing systolic BP.

PMID- 14573339
TI  - Risk terminology--a platform for common understanding and better communication.
AB  - The sciences analyzing and describing risks are relatively new and developing,
      and the associated terminologies are developing as well. This has led to
      ambiguity in the use of terms, both between different risk sciences and between
      the different parties involved in risk debates. Only recently, major vocabularies
      have been compiled by authoritative agencies. Some of these vocabularies are
      examined and explained based on a division into fundamental and action oriented
      risk terms. Fundamental terms are associated with description and
      characterization of the chemical, biological and physical processes leading from
      risk source(s) to possible consequences/effects. The approach to these terms is
      based on a cause-effect skeleton. The action oriented terms cover administrative,
      scientific, sociological, etc. processes associated with the work of identifying,
      characterizing, regulating and communicating risks in the society, and their
      internal connection and iterative character have been illustrated. Focus is laid
      on engineering and toxicological risks, but to some extent, the thoughts
      presented may be extrapolated to other areas. Differences in applied terminology
      probably cannot be eliminated, but they can be identified and clarified for
      better understanding. With the present paper, the authors hope to contribute to
      reducing the probability of derailing risk discussions from the risk issue
      itself.

PMID- 14573340
TI  - Shallow layer simulation of heavy gas released on a slope in a calm ambient. Part
      I. Continuous releases.
AB  - Although much research considers heavy gas dispersion over flat ground, less is
      known about the physics of dense gas dispersion on a slope. Here, the
      appropriateness of shallow layer models for the simple case of releases over a
      slope in a calm ambient is assessed. This two-part paper assesses the value of
      shallow layer modelling using the established shallow layer model TWODEE [J.
      Hazard. Mater. 66 (3) (1999) 211; J. Hazard. Mater. 66 (3) (1999) 227; J. Hazard.
      Mater. 66 (3) (1999) 239] and the experimental results of Schatzmann et al. [M.
      Schatzmann, K. Marotzke, J. Donat, Research on continuous and instantaneous heavy
      gas clouds, contribution of sub-project EV 4T-0021-D to the final report of the
      joint CEC project, Technical Report, Meteorological Institute, University of
      Hamburg, February 1991]. Part I considers continuous releases, and part II
      considers instantaneous releases; both use the same model with the same
      entrainment coefficients. For continuous releases, cloud arrival times are
      generally well predicted, and cloud concentrations are generally correct to
      within a factor of two. Shallow layer models thus appear to be capable of
      physically accurate simulation of continuous releases over a slope in a calm
      ambient.

PMID- 14573341
TI  - Shallow layer simulation of heavy gas released on a slope in a calm ambient. Part
      II. Instantaneous releases.
AB  - This paper assesses the value of shallow layer modelling for instantaneous
      releases of heavy gas over a slope using the established computer model TWODEE
      [R.K.S. Hankin, Heavy gas dispersion over complex terrain, Ph.D. thesis,
      Cambridge University, 1997; J. Hazard. Mater. 66 (1999) 211; J. Hazard. Mater. 66
      (1999) 227; J. Hazard. Mater. 66 (1999) 239] and the experimental results of
      Schatzmann et al. [M. Schatzmann, K. Marotzke, J. Donat, Research on continuous
      and instantaneous heavy gas clouds, Contribution of sub-project EV 4T-0021-D to
      the final report of the joint CEC project, Technical report, Meteorological
      Institute, University of Hamburg, February 1991]. This is the second of a two
      part paper; part I considered continuous releases using the same model, using the
      same entrainment parameters. Schatzmann et al. carried out instantaneous releases
      of heavy gas over three slopes; each experiment was repeated five times under
      nominally identical conditions. The goodness-of-fit measures (GFMs) of Hanna et
      al. [Atmos. Environ. 27A (15) (1993) 2265] are generalized to account for the
      multiple releases carried out by Schatzmann et al. Using these statistical GFMs,
      predicted peak concentrations are generally correct to within a factor of two;
      and cloud arrival times are generally late.

PMID- 14573342
TI  - Ozonation and H2O2/UV treatment of clofibric acid in water: a kinetic
      investigation.
AB  - The presence of pharmaceuticals or their active metabolites in surface and ground
      waters has been recently reported as mainly due to an incomplete removal of these
      pollutants in sewage treatment plants (STP). Advanced oxidation processes may
      represent a suitable tool to reduce environmental release of these species by
      enhancing the global efficiency of reduction of pharmaceuticals in the municipal
      sewage plant effluents. The present work aims at assessing the kinetics of
      abatement from aqueous solutions of clofibric acid (a metabolite of the blood
      lipid regulator clofibrate) which has been found in surface, ground and drinking
      waters. Ozonation and hydrogen peroxide photolysis are capable of fast removal of
      this species in aqueous solution, with an almost complete conversion of the
      organic chlorine content into chloride ions for the investigated reaction
      conditions. A validation of assessed kinetics at clofibric acid concentrations as
      low as those found in STP effluents is presented for both systems.

PMID- 14573343
TI  - Anodic oxidation with doped diamond electrodes: a new advanced oxidation process.
AB  - Boron-doped diamond anodes allow to directly produce OH* radicals from water
      electrolysis with very high current efficiencies. This has been explained by the
      very high overvoltage for oxygen production and many other anodic electrode
      processes on diamond anodes. Additionally, the boron-doped diamond electrodes
      exhibit a high mechanical and chemical stability. Anodic oxidation with diamond
      anodes is a new advanced oxidation process (AOP) with many advantages compared to
      other known chemical and photochemical AOPs. The present work reports on the use
      of diamond anodes for the chemical oxygen demand (COD) removal from several
      industrial wastewaters and from two synthetic wastewaters with malic acid and
      ethylenediaminetetraacetic (EDTA) acid. Current efficiencies for the COD removal
      between 85 and 100% have been found. The formation and subsequent removal of by
      products of the COD oxidation has been investigated for the first time.
      Economical considerations of this new AOP are included.

PMID- 14573344
TI  - Effects of adsorbents and copper(II) on activated sludge microorganisms and
      sequencing batch reactor treatment process.
AB  - Wastewater treatment systems employing simultaneous adsorption and biodegradation
      processes have proven to be effective in treating toxic pollutants present in
      industrial wastewater. The objective of this study is to evaluate the effect of
      Cu(II) and the efficacy of the powdered activated carbon (PAC) and activated rice
      husk (ARH) in reducing the toxic effect of Cu(II) on the activated sludge
      microorganisms. The ARH was prepared by treatment with concentrated nitric acid
      for 15 h at 60-65 degrees C. The sequencing batch reactor (SBR) systems were
      operated with FILL, REACT, SETTLE, DRAW and IDLE modes in the ratio of
      0.5:3.5:1:0.75:0.25 for a cycle time of 6 h. The Cu(II) and COD removal
      efficiency were 90 and 85%, respectively, in the SBR system containing 10 mg/l
      Cu(II) with the addition of 143 mg/l PAC or 1.0 g PAC per cycle. In the case of
      715 mg/l ARH or 5.0 g ARH per cycle addition, the Cu(II) and COD removal
      efficiency were 85 and 92%, respectively. ARH can be used as an alternate
      adsorbent to PAC in the simultaneous adsorption and biodegradation wastewater
      treatment process for the removal of Cu(II). The specific oxygen uptake rate
      (SOUR) and kinetic studies show that the addition of PAC and ARH reduce the toxic
      effect of Cu(II) on the activated sludge microorganisms.

PMID- 14573345
TI  - Stu2p and XMAP215: turncoat microtubule-associated proteins?
AB  - The dynamics of microtubule-based (MT) cytoskeletons are controlled by a variety
      of accessory proteins: microtubule-associated proteins (MAPs), which usually
      stabilize MTs, and microtubule-destabilizers. Two related MAPs, XMAP215 and
      Stu2p, are known to stabilize MTs. However, recent studies report that these
      proteins have a MT-destabilizing function as well. Here we discuss the
      implications of these reports.

PMID- 14573346
TI  - Proteasome degradation: enter the substrate.
AB  - Cells depend upon the regulated destruction of their various proteins to maintain
      homeostasis and change their metabolic state. A key component of this process is
      the proteasome - a large multisubunit protease whose catalytic sites are
      sequestered within a central chamber. Entry of substrates into proteasomes is
      regulated by activators and is generally thought to proceed sequentially,
      starting from one end of the substrate polypeptide. This conventional view is
      expanded by a recent paper, which indicates that some unfolded substrates can
      open the entrance to the proteolytic chamber in the absence of an activator and
      can enter the proteasome in a hairpin conformation to allow limited proteolysis
      of internal segments.

PMID- 14573347
TI  - Ran in the spindle checkpoint: a new function for a versatile GTPase.
AB  - The small GTPase Ran has a well-established role in nucleocytoplasmic
      trafficking. In recent years, the repertoire of Ran has expanded to include
      regulation of spindle assembly, formation of the nuclear envelope and DNA
      replication. Now, new studies further extend the role of Ran to regulating the
      spindle checkpoint during mitosis.

PMID- 14573348
TI  - Septate and paranodal junctions: kissing cousins.
AB  - A series of recent publications significantly advances our knowledge about the
      evolution and composition of septate junctions in arthropod and chordate species.
      These papers indicate that insect septate junctions share several structural and
      functional components with paranodal junctions, which join myelinating glial
      cells to axons in the vertebrate nervous system, and that both probably evolved
      from a common ancestral precursor.

PMID- 14573349
TI  - Spindle asymmetry: a compass for the cell.
AB  - Spatial coordination of the cell-division axis with cellular polarity and/or with
      the position of neighboring cells is crucial for embryonic development,
      organogenesis and tissue homeostasis. In most cell types, the position of the
      mitotic spindle at the onset of anaphase dictates the orientation of the division
      axis; in unicellular organisms, it plays an important role in chromosome
      segregation. Cortical factors play a key role in the orientation of the spindle.
      Recent data from yeast reveal that the spindle does not passively react to
      cortical signals but actively interprets them to find its correct position. We
      review the data leading to a "compass model" for spindle positioning and discuss
      its potential generality.

PMID- 14573350
TI  - Quantitative cell biology with the Virtual Cell.
AB  - Cell biological processes are controlled by an interacting set of biochemical and
      electrophysiological events that are distributed within complex cellular
      structures. Computational models, comprising quantitative data on the interacting
      molecular participants in these events, provide a means for applying the
      scientific method to these complex systems. The Virtual Cell is a computational
      environment designed for cell biologists, to facilitate the construction of
      models and the generation of predictive simulations from them. This review
      summarizes how a Virtual Cell model is assembled and describes the physical
      principles underlying the calculations that are performed. Applications to
      problems in nucleocytoplasmic transport and intracellular calcium dynamics will
      illustrate the power of this paradigm for elucidating cell biology.

PMID- 14573351
TI  - A dynamic bacterial cytoskeleton.
AB  - Actin and tubulin are the major components of the cytoskeleton that pervades the
      cytoplasm of all eukaryotic cells. These proteins were traditionally thought not
      to be present in prokaryotes, but structural and functional homologues of tubulin
      (FtsZ) and actin (MreB) are now known to be present virtually throughout the
      eubacteria and in some archae. FtsZ protein is a key player in cell division of
      bacteria and some eukaryotic organelles. MreB proteins are involved in the
      regulation of cell shape and the segregation of some bacterial plasmids, and
      might have a range of other functions. Recent data demonstrate that the bacterial
      proteins are, like their eukaryotic counterparts, highly dynamic. Here, we review
      the general properties and functions of actin and tubulin homologues in bacteria,
      their dynamic behaviour and the implications for understanding cell division and
      morphogenesis in bacteria.

PMID- 14573353
TI  - Tropomodulins: life at the slow end.
AB  - Dynamic exchange of actin monomers at filament ends is crucial for the functional
      architecture of many cytoskeletal-dependent processes. Recent evidence indicates
      that tropomodulins (Tmods), a conserved family of actin-capping proteins that
      bind to the pointed (slow-growing) end of actin filaments, regulate a variety of
      actin structures, including dynamic actin networks found in some motile cells.
      Actin structures that are more stable, such as sarcomeric thin filaments, require
      capping by Tmods to specify filament lengths and to provide filament stability.
      Here, we discuss the functional differences between the capping of pointed and
      barbed ends within the context of these actin-filament systems, and how Tmods
      uniquely contribute to their regulation and organization.

PMID- 14573352
TI  - Functional architecture of the nucleus: organizing the regulatory machinery for
      gene expression, replication and repair.
AB  - The organization and sorting of regulatory information for transcription,
      replication and repair depends on components of nuclear architecture. It is
      necessary, therefore, to understand cellular processes within the context of
      intranuclear microenvironments that mediate the focal assembly of the machinery
      for transcription, replication and repair and which facilitate the orchestration
      of these essential processes. Here, we discuss how nuclear anatomy supports the
      temporal and spatial coordination of regulatory protein recruitment for
      combinatorial control.

PMID- 14573354
TI  - Genetic engineering of Pichia pastoris to humanize N-glycosylation of proteins.
AB  - The yeast Pichia pastoris is used extensively as the host cell for large-scale
      production of secreted recombinant proteins. Many proteins of pharmaceutical
      importance are N-glycosylated, and therefore require an expression host that
      yields N-linked oligosaccharides that are structurally and functionally identical
      to the human counterpart. The recent report by Choi et al. describes the use of
      combinatorial genetic libraries to alter the N-glycosylation pathway in P.
      pastoris to yield N-linked oligosaccharides with hybrid structures that are the
      same as the intermediates of mammalian-protein N-glycosylation. In view of recent
      progress in this area, the production of complex human glycans in yeasts is
      anticipated.

PMID- 14573356
TI  - Delivering the vaccination mail.
AB  - The impact of preventative and therapeutic vaccines continues to expand in the
      fields of infectious disease and cancer, but their full potential is currently
      limited by drug-delivery challenges. Synthetic delivery systems that incorporate
      principles of biological design could improve vaccine efficacy significantly. A
      recent paper by Murthy et al. demonstrates that microgels engineered on the nano
      scale and designed to degrade at the mildly acidic pH of the phagosomal
      compartment can enhance protein-antigen entry into the cytoplasmic major
      histocompatibility complex (MHC) class 1 processing pathway.

PMID- 14573355
TI  - Sugar coating extends half-lives and improves effectiveness of cytokine hormones.
AB  - Recombinant human erythropoietin (rhEPO) is an effective and widely used
      therapeutic agent that is produced by bioengineering. Modification of the rhEPO
      protein by glycoengineering increased its already abundant N-glycosylation, which
      enhances its erythropoietic activity in vivo by decreasing its metabolic
      clearance. Elliott et al. recently reported increased in vivo activities of
      thrombopoietin (Mpl ligand) and leptin following carbohydrate addition to both,
      which suggests that such glycoengineering could be applied to a variety of
      hormones, cytokines and growth factors.

PMID- 14573357
TI  - Absolute systems biology--measuring dynamics of protein modifications.
AB  - Mass spectrometry is already established as the method of choice for protein
      identification. Hitherto, a major limitation of mass spectrometry was the
      inability to quantitate protein levels. With the development of novel methods,
      such as the AQUA method by Gerber et al., this hurdle has finally been overcome,
      unleashing the power of mass spectrometry to study protein dynamics in cells.

PMID- 14573358
TI  - Amphibian and mammal somatic-cell cloning: different species, common results?
AB  - Since the production of Dolly the sheep cloning methods for somatic cells have
      been thoroughly described and are becoming routine. However, the rate at which
      live clones are produced remains low in all mammalian species tested so far.
      Remarkably, irrespective of the cloning protocol or the donor-cell type, all
      clones display common abnormalities, particularly in the placenta. The process is
      also complicated by early mortality of somatic-cell clones and the founder
      mammalian clone, Dolly the sheep, died in February 2003 aged six years. Based on
      published data and on our own experience, our view is that mammalian somatic-cell
      cloning and the pioneer nuclear-transfer data from amphibians have much in
      common. We suggest that the only way to improve nuclear reprogramming is to
      modify the chromatin structure of somatic cells before nuclear transfer, to
      provide the oocyte with a chromosomal structure that is more compatible with the
      natural reprogramming machinery of the oocyte.

PMID- 14573359
TI  - Directed evolution of enzymes for applied biocatalysis.
AB  - Directed evolution has rapidly emerged as a powerful new strategy for improving
      the characteristics of enzymes in a targeted manner. By coupling various
      protocols for generating large variant libraries of genes, together with high
      throughput screens that select for specific properties of an enzyme, such as
      thermostability, catalytic activity and substrate specificity, it is now possible
      to optimize biocatalysts for specific applications. However, further work is
      required to broaden the range of screens that can be used, particularly in terms
      of reaction type, such as hydroxylation and carbon-carbon bond formation, and
      functional characteristics, such as enantioselectivity and regioselectivity, so
      that directed evolution can be used in a routine manner for biocatalyst
      development.

PMID- 14573360
TI  - Apoptosis: target for novel drugs.
AB  - Targeting apoptotic cell death pathways provides wide-ranging opportunities for
      the discovery and development of novel drugs. Some targeted therapies that
      selectively induce apoptosis in cancer cells are already marketed, and numerous
      pro-apoptotic drugs for treating cancer are currently being developed. The anti
      apoptotic drugs that are most advanced in development are targeting acute disease
      indications such as stroke, myocardial infarction and sepsis, in which the role
      of apoptosis has been best defined and inhibitors of the apoptotic pathway have
      shown activity in various animal models. In the future, novel drugs might also
      result from an understanding of apoptotic pathways in chronic disorders.

PMID- 14573362
TI  - Genetically modified probiotics in foods.
AB  - Probiotics have many potential therapeutic uses, but have not been universally
      accepted because of a lack of understanding of their action. Lactic acid bacteria
      (LAB) have been modified by traditional and genetic engineering methods to
      produce new varieties. Modern techniques of molecular biology have facilitated
      the identification of probiotic LAB strains, but only a few LAB have been
      modified by recombinant-DNA technology because of consumer resistance to their
      introduction to markets, especially in Europe.

PMID- 14573361
TI  - Domain antibodies: proteins for therapy.
AB  - Occurring naturally in "heavy chain" immunoglobulins from camels, and now
      produced in fully human form, domain antibodies (dAbs) are the smallest known
      antigen-binding fragments of antibodies, ranging from 11 kDa to 15 kDa. dAbs are
      the robust variable regions of the heavy and light chains of immunoglobulins (VH
      and VL respectively). They are highly expressed in microbial cell culture, show
      favourable biophysical properties including solubility and temperature stability,
      and are well suited to selection and affinity maturation by in vitro selection
      systems such as phage display. dAbs are bioactive as monomers and, owing to their
      small size and inherent stability, can be formatted into larger molecules to
      create drugs with prolonged serum half-lives or other pharmacological activities.

PMID- 14573364
TI  - Cyanobacterial postgenomic research and systems biology.
AB  - The genomic era brought with it the capacity to unlock complex interactions in
      organisms and biological systems. Currently, by exploiting genomic and associated
      protein information through in silico analyses, postgenomic research is
      developing rapidly. This field, which encompasses functional genomics, structural
      genomics, transcriptomics, pharmacogenomics, proteomics and metabolomics, allows
      for a systems-wide approach to biological studies. To date, bacterial postgenomic
      research has focused mainly on a few representative pathogenic species, leaving
      the vast majority of the microbial community relatively overlooked. Amongst the
      under-represented microorganisms are the cyanobacteria, which are important for
      their beneficial natural product production, bioremediation and energy
      applications. Here, we highlight the current status of cyanobacterial postgenomic
      research and assess the potential for future metabolic engineering and "cell
      factory" or "microbial cell" development.

PMID- 14573365
TI  - Muscle fiber conduction velocity estimation by using normalized peak-averaging
      technique.
AB  - In order to compute the muscle fiber conduction velocity (MFCV) and to clarify
      how action potentials are conducted, the normalized peak-averaging technique
      (NPAT) was newly employed together with computer softwares. Twelve pairs of
      surface electromyograms were selected from biceps brachii muscles during
      contraction at a level of 50% of the maximum voluntary isometric contraction in
      seven healthy volunteers. The techniques to compute MFCV from the time delay of
      the peaks (P-NPAT) and from the cross correlation (CC-NPAT) of averaged pulses
      were compared to the cross-correlation technique (CCT). The spread rate of
      averaged pulses was computed to estimate the spread of MFCVs in different motor
      units. Tri-phasic averaged pulses were obtained clearly by averaging more than
      500 detected pulses. The P-NPAT and CC-NPAT highly correlated with the CCT in the
      computed MFCVs. The MFCVs obtained by P-NPAT were generally larger than those
      obtained by CCT, and the spread rates had in the definite values. These results
      suggest that the MFCV could be computed and the spread of MFCVs would be
      estimated from averaged pulses. The MFCV of a patient with myotonic dystrophy was
      also studied, and it was suggested that the NPAT would be clinically useful.

PMID- 14573366
TI  - Influences of illusionary position perception on anticipatory postural control
      associated with arm flexion.
AB  - We examined the effect of illusionary perception on anticipatory postural control
      associated with arm flexion with subjects in a standing position, using vibration
      stimulation of the Achilles' tendon. Arm flexion was performed five times under
      each of the following conditions: (1) quiet standing, (2) vibration of the
      Achilles' tendon at 100 Hz frequency and 1.5 mm amplitude with the trunk fixed by
      a stopper during quiet standing, and (3) a perceived standing position during
      vibration. The reproduced positions were located forward by about 20% of the foot
      length compared with the quiet standing position; these positions showed no
      significant differences among the five trials. In the first trial of arm flexion
      during vibration, the biceps femoris began activating approximately 40 ms before
      the anterior deltoid. The same time difference between activation of the two
      muscles was observed in the reproduced condition. As the vibration trials were
      repeated, this activation timing approached the value in the quiet standing
      condition. In both the biceps femoris and erector spinae, the mean amplitude of
      electromyogram for the first 50 ms after the start of activation did not differ
      significantly among the three conditions.

PMID- 14573363
TI  - Biological applications of protein transduction technology.
AB  - The impermeable nature of the cell membrane to peptides, proteins, DNA and
      oligonucleotides limits the therapeutic potential of these biological agents.
      However, the recent discovery of short cationic peptides that cross the plasma
      membrane efficiently is opening up new possibilities for the intracellular
      delivery of such agents. These peptides are commonly referred to as protein
      transduction domains (PTDs) and are successfully used to transport heterologous
      proteins, peptides and other types of cargo into cells. Several recent reports
      have used the membrane transducing technology in vivo to deliver biologically
      active cargo into various tissues. This review discusses the structure of the
      most commonly used PTDs and how their ability to transduce membranes is used to
      regulate biological functions. It also considers future directions and the
      potential of this technology to move from the laboratory into the clinic.

PMID- 14573367
TI  - Normalisation of gait EMGs: a re-examination.
AB  - The purpose of this study was to compare four different methods of normalising
      electromyograms (EMGs) recorded during normal gait. Comparisons were made between
      the amplitude, intra-individual variability and inter-individual variability of
      EMGs. Surface EMGs were recorded from the biceps femoris, semitendinosus, vastus
      lateralis and vastus medialis of ten males and two females while they walked on a
      treadmill at a self-selected speed. EMGs from the same muscles were subsequently
      recorded during isometric maximal voluntary contractions (MVCs) and concentric,
      isokinetic MVCs that were performed between 0.52 and 7.85 rad x s(-1) on a BIODEX
      dynamometer. EMGs were also recorded during eccentric, isokinetic MVCs between
      0.52 and 2.62 rad x s(-1). Gait EMGs were then normalised at 2% intervals of the
      gait cycle by expressing them as a percentage of the following reference values:
      the mean (mean dynamic method) and the peak (peak dynamic method) EMG from the
      intra-individual ensemble average; the EMG from an isometric MVC (isometric MVC
      method); and the EMG from an isokinetic MVC that occurred with the same muscle
      action, length and velocity of musculotendinous unit as the gait EMGs (isokinetic
      MVC method). The isokinetic MVC method produced significantly greater (P<0.05)
      intra-individual variability compared to the other methods when it was measured
      using the variance ratio. Inter-individual variability of gait EMGs, again
      measured using the variance ratio, was also greatest when they were normalised
      using the isokinetic MVC method. The pattern and amplitude of EMGs normalised
      using the isometric MVC method and the isokinetic MVC method were very similar
      (root mean square difference and absolute difference both less than 3%). It was
      concluded that the isokinetic MVC method should not be adopted by gait
      researchers or clinicians as it does not reduce intra- or inter-individual
      variability anymore than existing normalisation methods, nor does it provide a
      more representative measure of muscle activation during gait than the isometric
      MVC method.

PMID- 14573368
TI  - The effect of falling height on muscle activity and foot motion during landings.
AB  - The aims of this study were: (a) to examine the effect of falling height on the
      kinematics of the tibiotalar, talonavicular and calcaneocuboid joints and (b) to
      study the influence of falling height on the muscle activity of the leg during
      landings. Six female gymnasts (height: 1.63 +/- 0.04 m, weight: 58.21 +/- 3.46
      kg) participated in this study. All six gymnasts carried out barefoot landings,
      falling from 1.0, 1.5 and 2.0 m height onto a mat. Three genlocked digital high
      speed video cameras (250 Hz) captured the motion of the left shank and foot.
      Surface electromyography (EMG) was used to measure muscle activity (1000 Hz) from
      five muscles (gastrocnemius medialis, tibialis anterior, peroneus longus, vastus
      lateralis and hamstrings) of the left leg. The kinematics of the tibiotalar,
      talonavicular and calcaneocuboid joints were studied. The lower-leg and the foot
      were modelled by means of a multi-body system, comprising seven rigid bodies. The
      falling height does not show any influence on the kinematics neither of the
      tibiotalar nor of the talonavicular joints during landing. The eversion at the
      calcaneocuboid joint increases with increasing falling height. When augmenting
      falling height, the myoelectric activity of the muscles of the lower limb
      increases as well during the pre-activation phase as during the landing itself.
      The muscles of the lower extremities are capable of stabilizing the tibiotalar
      and the talonavicular joints actively, restricting their maximal motion by means
      of a higher activation before and after touchdown. Maximal eversion at the
      calcaneocuboid joint increases about 52% when landing from 2.0 m.

PMID- 14573369
TI  - Muscle activation patterns of selected lower extremity muscles during stepping
      and cutting tasks.
AB  - Lower extremity muscle activations during crossover and side step cut tasks are
      hypothesized to play an important role in controlling knee motion, and therefore,
      impact the design of knee injury prevention and rehabilitation programs. However,
      the contribution of lower extremity muscles to frontal and transverse plane
      moments during cutting tasks is unclear. The purpose of this study was to compare
      the muscle activation patterns of selected lower extremity muscles (vastus
      lateralis, medial/lateral hamstrings and medial/lateral gastrocnemius) of
      subjects performing a stepping down and side step cut, a stepping down and
      crossover cut and an equivalent straight ahead task. Ground reaction force was
      used to determine the cut angle, stance time and compare the lower limb loading
      during each task. Electromyography data during all tasks were normalized to the
      average activation during the straight ahead tasks to determine relative changes
      in muscle activation between the straight ahead and different cut styles
      (crossover and side step). There were no differences in the pattern of muscle
      activation of the vastus lateralis, or lateral hamstring muscles when comparing
      the cutting tasks to the equivalent straight ahead task. However, the crossover
      cut task resulted in significantly higher muscle activation of the medial
      hamstrings and lateral gastrocnemius muscles relative to both the side step cut
      and straight ahead tasks. These results suggest the medial/lateral hamstrings and
      medial/lateral gastrocnemius play a role in transverse and frontal plane control
      during cut tasks.

PMID- 14573370
TI  - Fatigue compensation during FES using surface EMG.
AB  - Muscle fatigue limits the effectiveness of FES when applied to regain functional
      movements in spinal cord injured (SCI) individuals. The stimulation intensity
      must be manually increased to provide more force output to compensate for the
      decreasing muscle force due to fatigue. An artificial neural network (ANN) system
      was designed to compensate for muscle fatigue during functional electrical
      stimulation (FES) by maintaining a constant joint angle. Surface electromyography
      signals (EMG) from electrically stimulated muscles were used to determine when to
      increase the stimulation intensity when the muscle's output started to drop. In
      two separate experiments on able-bodied subjects seated in hard back chairs,
      electrical stimulation was continuously applied to fatigue either the biceps
      (during elbow flexion) or the quadriceps muscle (during leg extension) while
      recording the surface EMG. An ANN system was created using processed surface EMG
      as the input, and a discrete fatigue compensation control signal, indicating when
      to increase the stimulation current, as the output. In order to provide training
      examples and test the systems' performance, the stimulation current amplitude was
      manually increased to maintain constant joint angles. Manual stimulation
      amplitude increases were required upon observing a significant decrease in the
      joint angle. The goal of the ANN system was to generate fatigue compensation
      control signals in an attempt to maintain a constant joint angle. On average, the
      systems could correctly predict 78.5% of the instances at which a stimulation
      increase was required to maintain the joint angle. The performance of these ANN
      systems demonstrates the feasibility of using surface EMG feedback in an FES
      control system.

PMID- 14573371
TI  - Design and responses of Butterworth and critically damped digital filters.
AB  - For many years the Butterworth lowpass filter has been used to smooth many kinds
      of biomechanical data, despite the fact that it is underdamped and therefore
      overshoots and/or undershoots data during rapid transitions. A comparison of the
      conventional Butterworth filter with a critically damped filter shows that the
      critically damped filter not only removes the undershooting and overshooting, but
      has a superior rise time during rapid transitions. While analog filters always
      create phase distortion, both the critically damped and Butterworth filters can
      be modified to become zero-lag filters when the data are processed in both the
      forward and reverse directions. In such cases little improvement is realized by
      applying multiple passes. The Butterworth filter has superior 'roll-off'
      (attenuation of noise above the cutoff frequency) than the critically damped
      filter, but by increasing the number of passes of the critically damped filter
      the same 'roll-off' can be achieved. In summary, the critically damped filter was
      shown to have superior performance in the time domain than the Butterworth
      filter, but for data that need to be double differentiated (e.g. displacement
      data) the Butterworth filter may still be the better choice.

PMID- 14573372
TI  - Mathematical models for fatigue minimization during functional electrical
      stimulation.
AB  - We previously reported the development of a force- and fatigue-model system that
      predicted accurately forces during repetitive fatiguing activation of human
      skeletal muscles using brief duration (six-pulse) stimulation trains. The model
      system was tested in the present study using force responses produced by longer
      duration stimulation trains, containing up to 50 pulses. Our results showed that
      our model successfully predicted the peak forces produced when the muscle was
      repetitively activated with stimulation trains of frequencies ranging from 20 to
      40 Hz, train durations ranging from 0.5 to 1 s, and varied pulse patterns. The
      predicted peak forces throughout each protocol matched the experimental peak
      forces with r2 values above 0.9 and predicted successfully the forces at the end
      of each protocol with <15% error for all protocols tested. The success of our
      model system further supports its potential use for the design of optimal
      stimulation patterns for individual users during functional electrical
      stimulation.

PMID- 14573373
TI  - Sleep apnea: sex, money and consequences.

PMID- 14573374
TI  - Gender differences in sleep apnea: epidemiology, clinical presentation and
      pathogenic mechanisms.
AB  - Sleep apnea syndromes are a common cause of sleepiness and neurocognitive
      impairment and have been implicated as an independent risk factor for
      cardiovascular disease. While both epidemiological and sleep clinic-based studies
      indicate that sleep apnea syndromes are more common in men than in women, the
      gender difference in prevalence is more marked within the sleep clinic. Reasons
      for the relative failure of women to attend sleep clinics and the
      pathophysiologic differences that give rise to the male predominance of sleep
      apnea syndromes are unknown. The purpose of this review was to examine the
      literature with regard to these aspects, to provide clinical guidance to improve
      the reduced attendance of women to sleep laboratories and to stimulate research
      interest into the causes of these differences.

PMID- 14573375
TI  - The efficacy of split-night sleep studies.
AB  - Positive airway pressure (PAP) therapy is the most commonly used medical modality
      to reverse the apneas, hypopneas and inspiratory flow-limited breaths which
      result in the oxyhemoglobin desaturation, altered sleep architecture, and daytime
      sleepiness representing the cardinal features of obstructive sleep apnea/hypopnea
      (OSA/H). Identifying optimal strategies to develop the initial positive airway
      prescription is of paramount importance to clinicians who evaluate patients with
      suspected OSA/H. In addition, with the growing appreciation of the clinical and
      physiologic importance of sleep-disordered breathing, there have been increasing
      demands on clinical resources to diagnose and treat these patients. The time,
      hardware, and personnel-intensive nature of in-laboratory polysomnography (PSG)
      are significant in light of the traditional paradigm that utilizes a full night
      PSG for a diagnostic evaluation and when indicated, another full night for PAP
      titration. Efforts to identify time and resource-conserving alternatives to this
      paradigm have focused on in-laboratory split-night studies, in which the
      diagnosis of OSA/H can be made, and a positive pressure prescription defined
      during a single overnight PSG. Case-control studies indicate that, when certain
      guidelines are applied, split-night PSGs result in prescription efficacy and
      patient adherence, which are comparable to the traditional two-night strategy.
      However, prospective, randomized trials designed with adequate power are required
      to further define the impact of a split-night strategy on clinical outcome. As
      more information becomes available regarding the factors that determine long-term
      adherence to positive pressure therapy, the potential for efficient, expeditious
      treatment, and cost savings with split-night sleep studies will likely receive
      greater attention.

PMID- 14573376
TI  - Sleep disordered breathing and nocturnal polyuria: nocturia and enuresis.
AB  - Although nocturnal voiding is frequently attributed to urologic disorders,
      nocturia and enuresis are also important symptoms of sleep-disordered breathing.
      However, polyuria can be elicited by obstructive sleep apnea as well as bedrest,
      microgravity and other experimental conditions where the blood volume is shifted
      centrally to the upper body. The nocturnal polyuria of sleep apnea is an evoked
      response to conditions of negative intrathoracic pressure due to inspiratory
      effort posed against a closed airway. The mechanism for this natriuretic response
      is the release of atrial natriuretic peptide due to cardiac distension caused by
      the negative pressure environment. This cardiac hormone increases sodium and
      water excretion and also inhibits other hormone systems that regulate fluid
      volume, vasopressin and the rennin-angiotensin-aldosterone complex. Treatment of
      sleep apnea and airway compromise has been shown to reverse nocturnal polyuria
      and thereby reduce or eliminate nocturia and enuresis. Thus, careful evaluation
      of nocturia and enuresis for evidence of nocturnal polyuria can increase the
      diagnostic certainty of referring primary care providers and sleep specialists.
      In addition, the resolution of these bothersome symptoms after treatment can
      contribute to patient satisfaction as well as reinforce treatment compliance.

PMID- 14573377
TI  - Genetic aspects and genetic epidemiology of parasomnias.
AB  - Parasomnias are undesirable phenomena associated with sleep. Many of them run in
      families, and genetic factors have been long suggested to be involved in their
      occurrence. This article reviews the present knowledge of the genetics of the
      major classical behavioral parasomnias as well as present results from genetic
      epidemiological studies. The level and type of evidence for genetic effects
      varies much from parasomnia to parasomnia. The genetic factors are best
      established in enuresis, with several linkages to chromosomal loci, but their
      functions are not so far known. Environmental causes and gene-environment
      interactions are most probably also of great importance in the origin of complex
      traits or disorders such as parasomnias.

PMID- 14573378
TI  - Sleep spindles: an overview.
AB  - Sleep spindles are a distinctive EEG phasic feature of NREM sleep and are
      prevalent during stage 2 as compared to slow wave sleep. While the
      neurophysiological mechanisms of spindle generation, that involves thalamic and
      corticothalamic networks, have been recently delineated and are briefly reviewed,
      their definitive functional meaning still remains to be elucidated. This review
      summarizes the present knowledge on visually scored and automatically detected
      spindles, as well as the literature on EEG power in the sigma band. Among the
      factors known to affect sleep spindles and sigma activity, their intra-cycle
      temporal dynamics, their time-course across sleep cycles, the reciprocal
      relationship with delta activity, the effects of sleep deprivation, of circadian
      factors and of ageing, and their role in information processing have been
      discussed. Moreover, specific attention has been paid to the existence of
      functionally and topographically distinct slow- and fast-spindles, also taking
      into account the presence of large inter-individual differences. Nevertheless,
      several fundamental issues remain to be elucidated: the physiological mechanisms
      controlling age-related changes in spindle parameters; the role of melatonin as a
      spindle-promoting agent; the relationships between plastic mechanisms (after
      stroke, or as a consequence of learning) and modifications in spindle activity;
      the possibility of using some spindle parameters as an index of the severity of
      developmental disorders in abnormal maturational processes.

PMID- 14573379
TI  - Integrating psychosocial and biomedical CPAP adherence models. A commentary on:
      "Improving CPAP use by patients with the sleep apnea/hypopnea syndrome (SAHS)"
      (HM Engleman & MR Wild).

PMID- 14573380
TI  - Improving CPAP use by patients with the sleep apnoea/hypopnoea syndrome (SAHS).

PMID- 14573381
TI  - Blockade of excitatory amino acid transporters in the rat hippocampus results in
      enhanced activation of group I and group III metabotropic glutamate receptors.
AB  - The idea that excitatory amino acid transporters (EAATs) can control the
      activation of specific metabotropic glutamate receptors (mGluRs) was investigated
      in rat hippocampal slices. Using the accumulation of inositol phosphates as a
      measure of group I mGluR activity, we have shown that the broad spectrum, non
      transportable EAAT blocker, TBOA, produces a significant shift to the left of
      agonist concentration-response curves. Moreover, this increase in potency did not
      occur if endogenous glutamate was enzymatically removed, suggesting a glutamate
      dependent mechanism. This shift in potency was shown to be NMDA and group II mGlu
      receptor independent. Additionally, experiments with selective antagonists
      indicated that the group I receptor responsible for the stimulation of inositol
      phosphate production in this preparation is likely to be mGluR5. Inhibition of
      forskolin-stimulated cyclic AMP (cAMP) production was used as an index of group
      II/III mGluR activity. TBOA produced a rightward shift of the forskolin
      concentration-response curve. A group III, but not a group II, mGluR agonist also
      produced this effect, suggesting that the TBOA-mediated increase in glutamate
      activates a receptor, which appears to be a member of the group III mGluR subset.
      This was confirmed by the observation that an antagonist of group III mGluRs,
      prevented the TBOA-induced rightward shift in forskolin potency. These results
      provide evidence of a role for EAATs in the regulation of mGluR5 and group III
      mGluRs in the rat hippocampus, which may have therapeutic implications.

PMID- 14573383
TI  - Valproate modifies spontaneous excitation and inhibition at cortical synapses in
      vitro.
AB  - The anticonvulsant, valproic acid (VPA), has a very wide spectrum of clinical
      activity and has conventionally been considered to act by enhancing inhibitory
      GABAergic activity, either by increasing GABA levels and its subsequent release
      or by enhancing postsynaptic GABA responses. However, the pharmacology of VPA is
      complex and other mechanisms may well contribute. In the present study, we
      examined the effect of the drug on the release of GABA and glutamate at synapses
      in the rat entorhinal cortex, using the whole-cell patch clamp technique to
      record spontaneous excitatory (sEPSCs) and inhibitory postsynaptic currents
      (sIPSCs). VPA reduced the frequency but not the amplitude of both spontaneous
      sEPSCs and sIPSCs, with a more pronounced effect on the former. However, VPA had
      no effect on miniature, monoquantal events recorded in the presence of TTX,
      suggesting that the reduction in release occurred via blockade of Na(+)-channels
      in the presynaptic neurones. In addition, VPA also prolonged the decay time of
      sIPSCs, and this effect was occluded by a benzodiazepine agonist, zolpidem. These
      data suggest that in addition to presynaptic effects on release, VPA can
      potentiate postsynaptic responses, possibly by interaction with the
      benzodiazepine regulatory site of the GABA(A) receptor.

PMID- 14573382
TI  - (-)-PHCCC, a positive allosteric modulator of mGluR4: characterization, mechanism
      of action, and neuroprotection.
AB  - Group-III metabotropic glutamate receptors (mGluR4, -6, -7, and -8) modulate
      neurotoxicity of excitatory amino acids and beta-amyloid-peptide (betaAP), as
      well as epileptic convulsions, most likely via presynaptic inhibition of
      glutamatergic neurotransmission. Due to the lack of subtype-selective ligands for
      group-III receptors, we previously utilized knock-out mice to identify mGluR4 as
      the primary receptor mediating neuroprotection of unselective group-III agonists
      such as L-AP(4) or (+)-PPG, whereas mGluR7 is critical for anticonvulsive
      effects. In a recent effort to find group-III subtype-selective drugs we
      identified (+/-)-PHCCC as a positive allosteric modulator for mGluR4. This
      compound increases agonist potency and markedly enhances maximum efficacy and, at
      higher concentrations, directly activates mGluR4 with low efficacy. All the
      activity of (+/-)-PHCCC resides in the (-)-enantiomer, which is inactive at
      mGluR2, -3, -5a, -6, -7b and -8a, but shows partial antagonist activity at
      mGluR1b (30% maximum antagonist efficacy). Chimeric receptor studies showed that
      the binding site of (-)-PHCCC is localized in the transmembrane region.Finally, (
      )-PHCCC showed neuroprotection against betaAP- and NMDA-toxicity in mixed
      cultures of mouse cortical neurons. This neuroprotection was additive to that
      induced by the highly efficacious mGluR1 antagonist CPCCOEt and was blocked by
      MSOP, a group-III mGluR antagonist. Our data provide evidence for a novel
      pharmacological site on mGluR4, which may be used as a target-site for
      therapeutics.

PMID- 14573384
TI  - Differential sensitivity of genetically Fast vs. Slow kindling rats strains to
      GABAergic convulsive agents.
AB  - Following selective breeding for seizure-proneness vs. seizure-resistance to
      amygdala kindling, two strains of rats were developed with non-overlapping
      kindling rates, i.e. the number of stimulations required to develop fully
      generalized convulsive seizures (Epilepsy Res. 35 (1999) 183). In the temporal
      cortices of these two strains, the local seizure thresholds to electrical
      stimulation have been reported to be approximately two times lower in the seizure
      prone (Fast kindling) compared to the seizure-resistant (Slow kindling) strain
      (McIntyre et al., 1999). In the present experiment, the pharmacological
      sensitivities of the two strains to three GABAergic antagonists,
      pentylenetetrazol, bicuculline and picrotoxin, were determined, and compared to
      the glycine antagonist, strychnine. Paralleling kindling epileptogenesis, naive
      rats of the Fast kindling strain developed convulsive seizures to doses of the
      GABAergic antagonists that were significantly (approximately 30%) lower than the
      naive Slow kindling strain. In contrast, there were no strain differences in
      their response to strychnine. These data indicate substantial GABAergic
      sensitivity differences between the two strains with an emphasis on forebrain
      mechanisms, which is consistent with other physiological and molecular data
      related to their differential profiles of epileptogenesis.

PMID- 14573385
TI  - Acute and chronic effects of corticosterone on 5-HT1A receptor-mediated
      autoinhibition in the rat dorsal raphe nucleus.
AB  - Corticosteroid modulation of 5-HT(1A) receptor function may contribute to the
      aetiology of affective disorders. To examine this modulation, the effects of
      acute and chronic corticosterone administration on 5-HT(1A) autoreceptor function
      were investigated using in vitro electrophysiology in the rat dorsal raphe
      nucleus (DRN). The magnitude and time course of the inhibitory response to a
      submaximal dose of 5-HT was not affected by acute application of either
      corticosterone (30-200 nM) or dexamethasone (100 nM) in vitro, when tested either
      in slices from control rats or rats adrenalectomised two weeks prior to
      recording. For chronic treatment, rats were supplied with drinking water
      containing corticosterone (50 microg/ml) or ethanol vehicle (0.5%) for 25-31
      days. The autoinhibitory response to 5-HT was significantly attenuated in the
      corticosterone-treated group; vehicle EC(50)=48+/-8 microM vs. corticosterone
      EC(50)=121+/-20 microM. Furthermore a subpopulation of 5-HT neurones from
      corticosterone-treated animals exhibited marked insensitivity to 5-HT. In situ
      hybridisation histochemistry showed that corticosterone did not affect the
      expression of mRNA encoding the 5-HT(1A) receptor or either the type 1 and type 3
      subunits of the G-protein linked inwardly rectifying K+ (GIRK) channel. However,
      GIRK2 subunit mRNA expression was significantly reduced. Thus, 5-HT(1A)
      autoreceptor function in the DRN is attenuated following chronic, but not acute,
      exposure to elevated corticosterone levels, and this effect may involve changes
      to the receptor-effector coupling mechanism.

PMID- 14573386
TI  - Comparison of effects of dual transporter inhibitors on monoamine transporters
      and extracellular levels in rats.
AB  - Compounds that block both serotonin (5-HT) and norepinephrine (NE) transporters
      have been proposed to have improved antidepressant efficacy. We compared the
      ability of four dual transporter inhibitors-chlorimipramine, duloxetine,
      milnacipran and venlafaxine-to block monoamine transporters in vitro and in vivo
      and increase extracellular monoamines in rat brain. Inhibition of radioligand
      binding to clonal human monoamine transporters in vitro and in vivo in rats was
      determined. Extracellular concentrations of 5-HT and NE in rat prefrontal cortex
      (PFC) were quantified using the microdialysis technique. All compounds blocked
      binding to human 5-HT and NE transporters, although chlorimipramine and
      venlafaxine had markedly greater affinity for 5-HT than NE transporters. In vivo,
      chlorimipramine and duloxetine potently blocked both transporters, milnacipran
      blocked both with lower potency and venlafaxine only blocked the 5-HT
      transporter. Chlorimipramine and duloxetine increased robustly and approximately
      equally monoamine extracellular concentrations. Milnacipran produced only small
      increases in NE, whereas venlafaxine increased 5-HT markedly at the lower doses
      and both monoamines at high doses. Thus, the dual transporter inhibitors blocked
      5-HT and NE transporters in vitro and in vivo with varying potency.
      Chlorimipramine, duloxetine, and high dose venlafaxine acted as dual transporter
      inhibitors in rat PFC and increased extracellular concentrations of the
      monoamines, indicating functional dual transporter inhibition.

PMID- 14573387
TI  - Intrastriatal administration of sigma ligands inhibits basal dopamine release in
      vivo.
AB  - In this study, using the new sigma(1/2) (sigma(1/2)) compound MR200, its parent
      drug haloperidol and the sigma ligand 1,3-di-o-tolylguanidine (DTG), we have
      investigated the role of striatal sigma receptors in the control of basal
      dopamine (DA) outflow, by coupling in vitro binding experiments and in vivo
      microdialysis in the striatum of halothane-anesthetized rats. MR200 with respect
      to haloperidol, exhibits high affinity for sigma(1) (1.5 nM) and sigma(2) (21.9
      nM) receptors, but only negligible affinity for DA receptors. Compared to DTG,
      MR200 has similar selectivity across neurotransmitter systems, and 46 times
      higher affinity for sigma(1) receptors. Intrastriatal application of MR200 at 10,
      but not 0.1 or 1 microM, elicited a pronounced decrease in striatal DA release (
      45% of control values). This inhibitory effect was preceded by a transient
      increase in DA release (+50% over baseline) after 100 microM MR200
      administration. DTG at 100, but not 10 microM, significantly reduced DA release (
      40%). Haloperidol, whilst increasing DA release at 1 microM, induced a delayed
      decrease in DA release after 10 microM application. Finally, haloperidol (10
      microM) did not modify the inhibitory effect of 10 microM MR200. These results
      show that striatal sigma receptors control striatal DA release in resting
      conditions.

PMID- 14573388
TI  - Opioid antagonists increase the dyskinetic response to dopaminergic agents in
      parkinsonian monkeys: interaction between dopamine and opioid systems.
AB  - The pathogenesis of levodopa-induced dyskinesias (LID) still remains obscure. It
      has been suggested that enhanced opioidergic transmission in striatal output
      pathways may play a role in the induction of LID. To test this hypothesis, we
      have investigated the effect of different doses of the opioid receptor
      antagonists, naloxone and naltrexone on the dyskinetic response to a D1 agonist
      SKF 82958, a D2 agonist quinpirole and L-3,4-dihydroxyphenylalanine (L-Dopa). We
      have used six female cynomolgus monkeys rendered parkinsonian by the toxin MPTP
      and presenting a stable parkinsonian syndrome. All responded to L-Dopa and had
      developed dyskinesias which were manifested with each dose. The parkinsonian
      syndrome and dyskinesias were evaluated for each animal and scored after the
      treatments. Locomotor activity was measured by an electronic motility monitoring
      system. Our results show that coadministration of naloxone or naltrexone with
      dopaminergic agents leads to a significant increase in the severity of
      dyskinesias without noticeable effect on the antiparkinsonian efficacy of the
      treatment. These results suggest that increased opioidergic transmission in the
      two major striatal output pathways in monkeys or humans with LID might be an
      attempt to dampen the effect of abnormal dopaminergic stimulation rather than the
      cause of dyskinesias.

PMID- 14573389
TI  - Molecular mechanisms of inhibition of nicotinic acetylcholine receptors by
      tricyclic antidepressants.
AB  - In addition to their well known actions on monoamine reuptake, tricyclic
      antidepressants have been shown to modulate ligand-gated ion channels (LGICs).
      Since the muscle nicotinic acetylcholine receptor (AChR) has been the model for
      studying structure-function relationships of LGICs, we analyzed the action of
      tricyclic antidepressants on this type of AChR at both single-channel and
      macroscopic current levels. We also determined their effects on ACh equilibrium
      binding and their interactions with the different conformational states of the
      AChR. Antidepressants produce a significant concentration-dependent decrease in
      the duration of clusters of single-channels (eight fold at 20 muM). They also
      decrease the peak amplitude and increase the decay rate of currents elicited by
      rapid perfusion of ACh to outside-out patches. In equilibrium binding assays,
      antidepressants promote the typical high-affinity desensitized state and inhibit
      binding of [piperidyl-3,4-(3)H (N)]-(N-(1-(2-thienyl)cyclohexyl)-3,4-piperidine
      ([(3)H]TCP) to its locus in resting and desensitized AChRs. The results indicate
      that tricyclic antidepressants: (i) interact with resting (closed), open, and
      desensitized channels; (ii) do not affect significantly channel opening and
      closing rates; (iii) do not act as fast open-channel blockers; (iv) inhibit
      activation of resting channels; and (v) may increase the rate of long-lived
      desensitization from the open state.

PMID- 14573390
TI  - Caffeine reduces hypnotic effects of alcohol through adenosine A2A receptor
      blockade.
AB  - The role of the adenosine A(2A) receptor in the hypnotic effects of ethanol was
      assessed in mice. The duration of the loss of righting reflex following acute
      ethanol administration was shorter for A(2A) receptor-deficient mice (A(2A)R KO)
      than for wild-type mice (A(2A)R WT), whereas the fall in body temperature was not
      different between the two phenotypes. In contrast, the duration of the loss of
      righting reflex was increased in A(2A)R KO mice versus controls after
      administration of pentobarbital. Dipyridamole, an inhibitor of adenosine uptake,
      increased the sleep time observed following administration of ethanol in CD1 mice
      and in A(2A)R WT but not in A(2A)R KO mice. SCH 58261, a selective A(2A) receptor
      antagonist, unlike DPCPX, a selective A(1) receptor antagonist, shortened the
      duration of the loss of righting reflex induced by ethanol, thus mimicking the
      lack of receptor in deficient mice. Finally, the non-selective adenosine receptor
      antagonist caffeine (25 mg/kg) reduced ethanol-induced hypnotic effects. These
      results indicate that the activation of A(2A) receptors that follows an increase
      in extracellular adenosine levels caused by the administration of high doses of
      ethanol plays a role in its hypnotic effects. Thus, A(2A) receptor antagonists
      may be useful therapeutic agents for alleviating ethylic coma.

PMID- 14573391
TI  - Elevated neuronal nitric oxide synthase expression in chronic haloperidol-treated
      rats.
AB  - Long-term administration of neuroleptic drugs, such as haloperidol, in the
      management of psychiatric disorders may adversely cause an irreversible
      neurological syndrome of tardive dyskinesia, which is associated with dopamine
      (DA(2)) receptor supersensitivity in the basal ganglia. Recent studies also
      indirectly suggest an involvement of nitric oxide synthase (NOS) in dopaminergic
      supersensitivity; however, chronic neuroleptic effects on neuronal NOS (nNOS)
      expression in the basal ganglia have not been reported. In this investigation, we
      treated rats with saline or haloperidol (1 mg/kg, s.c.) daily for 21 days. Five
      days later, we detected a significant increase of NOS activity in the striatum of
      haloperidol-treated rats when compared to saline controls. This effect was
      associated with elevated levels of nNOS mRNA and protein expression in the
      striatum, but not in the nucleus accumbens, as evidenced by the use of in situ
      hybridization, Western blot and immunohistochemical techniques. The involvement
      of the nNOS system after chronic haloperidol treatment coincides with increases
      of striatal DA(2) receptor sites, calmodulin kinase II activity, animal locomotor
      and stereotypy behaviors. This study suggests an integral role between nNOS,
      DA(2) receptor and calmodulin system in the development of dopaminergic
      behavioral supersensitivity resulting from chronic neuroleptic drug treatment.
      Furthermore, the toxic effect of chronic haloperidol on NOS system selectivity
      takes place in the neostriatum.

PMID- 14573392
TI  - Spatial requirements for TrkA kinase activity in the support of neuronal survival
      and axon growth in rat sympathetic neurons.
AB  - Nerve growth factor (NGF) interacts with its receptor tyrosine kinase, TrkA, at
      axon terminals to produce local signals within axon terminals and retrograde
      signals to the neuronal cell body. According to prevalent theory, retrograde
      signaling requires the retrograde transport to the cell bodies of signaling
      endosomes containing activated TrkA complexed with NGF. Alternative mechanisms in
      which retrograde signals reach the cell bodies unaccompanied by NGF may or may
      not require activated TrkA in the cell body. To help distinguish this
      possibility, we investigated the spatial requirements of TrkA kinase activity for
      neuronal survival and axon growth in rat sympathetic neurons supported by NGF
      provided only to distal axons. Inhibition of local TrkA kinase activity in the
      distal axons by K252a blocked local axon growth and induced apoptosis. Although
      local application of K252a to cell bodies/proximal axons resulted in a sustained
      loss of phosphorylated TrkA from the cell bodies/proximal axons, the neurons
      survived, and growth of the distal axons was not inhibited. These results suggest
      that TrkA kinase activity in distal axons, but not in the cell bodies, is
      required for both local growth and retrograde survival signaling. These results
      support the hypothesis that retrograde signals can be carried by mechanisms
      downstream of TrkA activity.

PMID- 14573393
TI  - Human catechol-O-methyltransferase down-regulation by estradiol.
AB  - Catechol-O-methyltransferase (COMT) is a crucial enzyme in dopamine and levodopa
      metabolism. Previously we reported that physiological concentrations of 17beta
      estradiol (E2) down-regulated steady-state 1.3-kb COMT mRNA levels in MCF-7
      cells. In this study, we investigated whether similar reductions occurred in a
      glial cell line (U138MG) and whether COMT protein and activity levels paralleled
      the reduction in COMT mRNA levels in MCF-7 cells. In addition, we explored the
      mechanism of E2 action. E2 had no effect on COMT mRNA levels in U138MG cells, but
      significantly reduced COMT protein and activity in MCF-7 cells (activity by 53%
      at 10(-7) M of E2, by 45% at 10(-8) M, and by 28% at 10(-9) M relative to non-E2
      treated cells). A specific estrogen receptor antagonist (ICI 182780) blocked
      these estrogenic effects. Estrogen receptor in nuclear extracts of MCF-7 cells,
      which were pretreated with E2 (10(-9) M) for 48 h, bound to the whole proximal
      and distal promoter regions, as determined by electrophoretic mobility shift
      analysis (EMSA). We propose that E2 decreased COMT activity through down
      regulation of its gene and protein expression mediated via ER interaction with
      response elements in the promoter region of the gene. Our findings may explain
      the lower of COMT activity in women compared to that in men, and, in part, the
      beneficial effects of E2 therapy in post-menopausal Parkinson's disease patients.

PMID- 14573397
TI  - What price, abdominal radiology?

PMID- 14573394
TI  - Contraction of isolated guinea-pig ileum by urotensin II via activation of
      ganglionic cholinergic neurons and acetylcholine release.
AB  - Urotensin II and its receptor are expressed in the gastrointestinal tract of
      mice, but the effects of urotensin II on the gastrointestinal functions have not
      been established. In the present study, we investigated the effects of human
      urotensin II on a segment of the guinea-pig ileum. The addition of urotensin II
      induced contraction of the ileum in concentration-manner (-log EC(50) value was
      8.13+/-0.21). The response by urotensin II was extracellular CaCl(2)-dependent
      and easily desensitized. Like nicotine, the contraction induced by 100 nM
      urotensin II was inhibited by treatment with atropine, hexamethonium, D
      tubocurarine, tetrodotoxin or hemicholinium-3, and enhanced by physostigmine.
      Treatment with omega-conotoxin GVIA (an inhibitor of N-type Ca(2+) channels, 300
      nM) inhibited 100 nM urotensin II- and 4 microM nicotine-, but not 3 microM
      acetylcholine-, induced contraction. Both urotensin II and nicotine stimulated
      [(3)H]choline release in a tetrodotoxin-sensitive manner from the prelabeled
      slices of the ileum. These findings suggest that urotensin II stimulated
      acetylcholine release from the ganglionic cholinergic neurons and thus stimulated
      contraction via muscarinic acetylcholine receptors in the guinea-pig ileum.
      Urotensin II receptor system in the myenteric neurons may regulate the
      gastrointestinal functions.

PMID- 14573399
TI  - Wrongful life.

PMID- 14573401
TI  - Point: Screening CT and modern economics.

PMID- 14573402
TI  - Counterpoint: Screening CT and modern economics.

PMID- 14573403
TI  - Pulsed tunable monochromatic X-ray beams from a compact source: new
      opportunities.

PMID- 14573405
TI  - Comparison of high-field-strength versus low-field-strength MRI of the shoulder.
AB  - OBJECTIVE: Previous studies have reported similar results of shoulder MRI versus
      arthroscopy for high-field-strength (1.5-T) and low-field-strength (0.2-T) units.
      We report our experience with the accuracy of high- versus low-field-strength
      units versus arthroscopy for detection of supraspinatus tendon tears and labral
      tears in the same patients. SUBJECTS AND METHODS. Three musculoskeletal
      radiologists prospectively interpreted shoulder MRIs from 40 patients who had a
      complete shoulder MRI examination on a 0.2-T system and limited imaging on a 1.5
      T unit. Proton-density axial and fat-saturated T2-weighted coronal and sagittal
      sequences were performed. Each radiologist interpreted the open unit images first
      and the high-field-strength images second. Results from 28 patients who also
      underwent arthroscopy were also compared with the MRI interpretations. All scans
      were then retrospectively reinterpreted by consensus of the three reviewers, who
      were unaware of the patient's name, results of previous MRI, or arthroscopy
      report (if any). RESULTS: High-field-strength images altered reviewers'
      interpretations of low-field-strength scans for nine of 40 patients. In four
      patients, full-thickness supraspinatus tendon tears could be diagnosed
      definitively on the high-field-strength unit but not on the open unit. Three
      labral tears and two superior labral anteroposterior lesions could be depicted
      definitively on the high-field-strength unit but not on the open unit. All tears
      were confirmed at arthroscopy. CONCLUSION: High-field-strength MRI units provide
      better spatial and contrast resolution and allow more accurate interpretations
      than low-field-strength units; these findings may affect clinical treatment.

PMID- 14573404
TI  - Quantitative assessment of diffusion abnormalities in benign and malignant
      vertebral compression fractures by line scan diffusion-weighted imaging.
AB  - OBJECTIVE: Acute vertebral collapse is common, and it is sometimes difficult to
      determine whether the cause is benign or malignant. Recently, diffusion-weighted
      imaging has been reported to be useful for differentiating the two types. The
      purpose of this study was to evaluate diffusion abnormalities quantitatively in
      benign and malignant compression fractures using line scan diffusion-weighted
      imaging. SUBJECTS AND METHODS. Line scan diffusion-weighted imaging was
      prospectively performed in 17 patients with 20 acute vertebral compression
      fractures caused by osteoporosis or trauma, in 12 patients with 16 vertebral
      compression fractures caused by malignant tumors, and in 35 patients with 47
      metastatic vertebrae without collapse. Images were obtained at b values of 5 and
      1,000 sec/mm(2). The apparent diffusion coefficient (ADC) was measured in
      vertebral compression fractures and metastatic vertebrae without collapse.
      RESULTS: The ADC (mean +/- SD) was 1.21 +/- 0.17 x 10(-3) mm(2)/sec in benign
      compression fractures, 0.92 +/- 0.20 x 10(-3) mm(2)/sec in malignant compression
      fractures, and 0.83 +/- 0.17 x 10(-3) mm(2)/sec in metastatic vertebral lesions
      without collapse. The ADC was significantly higher in benign compression
      fractures than in malignant compression fractures (p < 0.01), although the two
      types showed considerable overlap. CONCLUSION: Although the quantitative
      assessment of vertebral diffusion provides additional information concerning
      compressed vertebrae, the benign and malignant compression fracture ADC values
      overlap considerably. Therefore, even a quantitative vertebral diffusion
      assessment may not always permit a clear distinction between benign and malignant
      compression fractures.

PMID- 14573406
TI  - Diabetic muscle infarction.

PMID- 14573407
TI  - MR arthrography of anterior cruciate ligament reconstruction grafts.
AB  - OBJECTIVE: Our objective was to determine the accuracy of MR arthrography for
      identification of tears of anterior cruciate ligament reconstruction grafts and
      for detection of localized anterior arthrofibrosis and impingement. MATERIALS AND
      METHODS: We retrospectively identified 27 patients (mean age, 31 years; range, 18
      45 years) with anterior cruciate ligament reconstruction who had undergone MR
      arthrography followed by arthroscopy within 1 year. Three radiologists
      independently reviewed the MR arthrograms for the presence or absence of graft
      tear, localized anterior arthrofibrosis, and impingement. RESULTS: Graft tears
      were identified with 100% sensitivity by all three reviewers with specificities
      of 100%, 89%, and 94%. Localized anterior arthrofibrosis was identified with 100%
      sensitivity by all reviewers, with specificities of 79%, 71%, and 38%.
      Impingement was detected with sensitivities and specificities of 83% and 100%,
      83% and 52%, and 33% and 90% by the three reviewers, respectively. Interobserver
      agreement was almost perfect for detection of graft tear (kappa = 0.83, 0.92, and
      0.83), was fair to moderate for detection of localized anterior arthrofibrosis
      (kappa = 0.50, 0.32, and 0.22), and was slight to fair for detection of
      impingement (kappa = 0.40, 0.08, and 0.35). CONCLUSION: MR arthrography can
      accurately depict the presence of anterior cruciate ligament graft tears.
      Localized anterior arthrofibrosis and graft impingement were less accurately
      detected and showed greater observer variability.

PMID- 14573408
TI  - Using dynamic sonography to diagnose extensor digitorum brevis manus.

PMID- 14573409
TI  - Complications of rotator cuff surgery in which bioabsorbable anchors are used.
AB  - OBJECTIVE: This study assessed the utility of MRI in patients with new or
      persistent pain after surgery with bioabsorbable rotator cuff anchors. SUBJECTS
      AND METHODS. Three musculoskeletal radiologists prospectively reviewed MRIs of 30
      patients with pain after rotator cuff repair with fixation by rotator cuff
      anchors. Each radiologist described the location of the rotator cuff anchors and
      whether the supraspinatus tendon was intact or not. MRI findings were correlated
      with second-look arthroscopy. Consensus MRI interpretations by the three
      radiologists were obtained retrospectively. RESULTS: Of the 30 patients, nine had
      dislodgement of the rotator cuff anchors from the humeral head along with a full
      thickness supraspinatus tendon retear. The dislodged rotator cuff anchor position
      could be determined on coronal and sagittal MRIs, providing the orthopedic
      surgeon a preoperative map for tendon reattachment and retrieval of the dislodged
      rotator cuff anchor. Four patients had loose rotator cuff anchors but intact
      supraspinatus tendons. Three patients had supraspinatus tendon retears, but the
      rotator cuff anchors were intact. In all 16 patients, arthroscopic findings
      confirmed MRI findings. Fourteen patients had intact rotator cuff anchors and
      intact supraspinatus tendons on MRI. Of these 14 patients, five had second-look
      arthroscopy confirming MRI findings. CONCLUSION: MRI is useful in the assessment
      of patients with persistent or new-onset pain after supraspinatus tendon repair
      with rotator cuff anchors. MRI provides a presurgical map for second-look
      arthroscopy to assess retear of the supraspinatus tendon and also aids in
      retrieval of dislodged rotator cuff anchors.

PMID- 14573410
TI  - Fluoroscopically guided scapulothoracic injections.

PMID- 14573411
TI  - Should the routine wrist examination for trauma be a four-view study, including a
      semisupinated oblique view?

PMID- 14573412
TI  - Sacral fractures: a potential pitfall of FDG positron emission tomography.
AB  - OBJECTIVE: Positron emission tomography (PET) with FDG is useful for tumor
      imaging, but false-positive results can occur. The purpose of this study is to
      describe three oncology patients with sacral fractures in whom FDG uptake in the
      sacrum increased on PET. CONCLUSION: Sacral fractures can show increased uptake
      of FDG on PET. Therefore, correlative cross-sectional imaging is necessary to
      avoid the erroneous diagnosis of sacral metastases on PET and prevent
      inappropriate treatment of patients.

PMID- 14573413
TI  - MRI features of intersection syndrome of the forearm.
AB  - OBJECTIVE: The purpose of this original report is to describe the MRI findings in
      patients with intersection syndrome of the forearm. CONCLUSION: Intersection
      syndrome is an overuse disorder of the dorsal distal forearm, presenting with
      particular symptoms and signs that may be clinically misdiagnosed. MRI can
      perform an important role in establishing the diagnosis. Peritendinous edema
      (peritendinitis) around the first and second extensor compartment tendons,
      extending proximally from the crossover point, is the most characteristic finding
      that should suggest a diagnosis of intersection syndrome. Chronic cases may be
      subtle and not show substantial MRI findings likely reflecting the development of
      a stenosing tenosynovitis.

PMID- 14573414
TI  - Imaging characteristics of spindle cell lipoma.
AB  - OBJECTIVE: The objective of this article is to define the imaging characteristics
      of spindle cell lipoma on MRI and CT. CONCLUSION: The diagnosis of spindle cell
      lipoma should be suggested when a well-defined complex fatty mass is found in the
      subcutis of a middle-aged man, especially if the mass is localized to the
      posterior neck. Intense enhancement of the nonadipose component further supports
      this diagnosis.

PMID- 14573415
TI  - Efficacy of epidural injections of Kenalog and Celestone in the treatment of
      lower back pain.
AB  - OBJECTIVE: Epidural corticosteroid injections have been used extensively to treat
      lower back pain, but the relative effectiveness of one corticosteroid versus
      another has never been reported in a large patient series. We retrospectively
      reviewed 597 patients who had epidural corticosteroid injections to determine any
      difference in Kenalog or Celestone efficacy. MATERIALS AND METHODS: We reviewed
      charts and self-reported pain score evaluations of 597 patients who received
      either Kenalog or Celestone Soluspan as an epidural injection for the treatment
      of lower back pain from 1997 to 2002 at our university hospital and affiliated
      Veterans Affairs hospital. Kenalog was used for the initial 2 years and Celestone
      was used for the next 3 years. Fluoroscopic guidance was used to confirm epidural
      location, and each patient was injected with a mixture of 5 mL of 0.5%
      preservative-free lidocaine and 2 mL of either Kenalog 40 mg/mL (triamcinolone
      acetonide injectable suspension) or Celestone Soluspan 6 mg/mL (betamethasone
      sodium phosphate and betamethasone acetate injectable suspension). Each patient
      was given a standardized pain evaluation sheet that used an 11-point scale for
      initial pain severity. Scoring of pain compared with baseline during the
      following 14 days was based on a 5-point scale of pain improvement or worsening.
      RESULTS: On days 0-3 after the procedure, no statistical significance in
      improvement of lower back and buttock pain was seen between groups. On day 7, 59%
      of Celestone recipients and 73% of Kenalog recipients showed improvement in lower
      back pain (p = 0.002, Pearson's chi-square test), and 58% of Celestone recipients
      and 75% of Kenalog recipients had improvement in leg or buttock pain (p < 0.001).
      On day 14, 54% of Celestone recipients and 71% of Kenalog recipients showed
      improvement in lower back pain (p < 0.001), and 54% of Celestone recipients and
      71% of Kenalog recipients had improvement in leg or buttock pain (p < 0.001).
      CONCLUSION: The epidural injection of Celestone Soluspan and Kenalog reduced
      lower back and radicular pain in more than half the patients, although Kenalog
      reduced pain in a significantly larger number of patients than Celestone Soluspan
      at 1 and 2 weeks after injection.

PMID- 14573416
TI  - Popliteal artery entrapment syndrome: role of imaging in the diagnosis.

PMID- 14573418
TI  - Characterization of lesions of the breast with proton MR spectroscopy: comparison
      of carcinomas, benign lesions, and phyllodes tumors.
AB  - OBJECTIVE: Proton MR spectroscopy is a recently described technique with high
      sensitivity and specificity for differentiating breast carcinoma from benign
      lesions. We evaluated the possible relationship between spectroscopy results and
      the tumor proliferative index, angiogenesis, and HER2/neu oncogene
      overexpression. SUBJECTS AND METHODS. We prospectively evaluated 19 breast
      carcinomas, 21 benign breast lesions (including 18 fibroadenomas, one fibrocystic
      change, one hamartoma, and one papilloma), and six phyllodes tumors (four benign,
      two of borderline malignancy) using proton MR spectroscopy. All lesions were
      larger than 1.5 cm. Tumor Ki-67 proliferative index, tumor angiogenesis, and
      HER2/neu oncogene overexpression were evaluated by immunohistochemistry of the
      histologic material. RESULTS: Spectroscopy findings were positive in 17 (89%) of
      19 carcinomas but negative for all benign lesions and phyllodes tumors
      (sensitivity, 89%; specificity, 100%). Significantly higher levels were obtained
      for all biologic parameters in carcinomas compared with benign lesions and
      phyllodes tumors. HER2/neu oncogene overexpression was present in 37% of
      carcinomas but not in other lesions. The two false-negative findings of breast
      carcinoma showed similar Ki-67 proliferative index and microvessel density
      compared with the remaining carcinomas, but both cases were negative for HER2/neu
      overexpression. CONCLUSION: Proton MR spectroscopy is useful in the in vivo
      characterization of breast masses when the lesion exceeds 1.5 cm in maximal
      dimension. Spectroscopy is unable to reveal benign breast lesions and phyllodes
      tumors of benign and borderline malignancy. We suggest that a false-negative
      spectroscopic result may be related to an absence of HER2/neu overexpression in
      carcinoma of the breast.

PMID- 14573419
TI  - Characterization of breast lesions with proton MR spectroscopy.

PMID- 14573420
TI  - Accuracy of MRI in the detection of residual breast cancer after neoadjuvant
      chemotherapy.
AB  - OBJECTIVE: This study was undertaken to evaluate the ability of MRI to accurately
      show residual primary breast malignancy in women treated with neoadjuvant
      chemotherapy. MATERIALS AND METHODS: Twenty-one patients with locally advanced
      primary breast carcinoma underwent contrast-enhanced MRI before and after
      treatment with neoadjuvant anthracycline-based chemotherapy. For each patient,
      the maximum extent of the MRI abnormality was measured both before and after
      treatment. These measurements were subsequently compared with physical
      examination findings and histologic results to determine the ability of MRI to
      accurately reveal tumor extent after neoadjuvant chemotherapy. RESULTS: MRI after
      chemotherapy showed a correlation coefficient of 0.75 with histology, which was
      better than physical examination (r = 0.61). MRI underestimated the extent of
      residual tumor in two patients by more than 1 cm (including one false-negative
      examination), was within 1 cm in 12 of 21 patients, and overestimated tumor
      extent by more than 1 cm in seven of 21 patients. CONCLUSION: MRI can show
      residual malignancy after neoadjuvant chemotherapy better than physical
      examination, particularly in patients who have not had a complete clinical
      response to therapy.

PMID- 14573421
TI  - Fast MRI-guided vacuum-assisted breast biopsy: initial experience.
AB  - OBJECTIVE: The purpose of this study was to evaluate a new method for performing
      MRI-guided vacuum-assisted breast biopsy in a study of lesions that had
      subsequent surgical excision. SUBJECTS AND METHODS. Twenty women scheduled for
      MRI-guided needle localization and surgical biopsy were prospectively entered in
      the study. MRI-guided biopsy was performed with a vacuum-assisted probe, followed
      by placement of a localizing clip, and then needle localization for surgical
      excision. Vacuum-assisted biopsy and surgical histology were correlated. RESULTS:
      Vacuum-assisted biopsy was successfully performed in 19 (95%) of the 20 women.
      The median size of 27 MRI-detected lesions that had biopsy was 1.0 cm (range, 0.4
      6.4 cm). Cancer was present in eight (30%) of 27 lesions and in six (32%) of 19
      women; among these eight cancers, five were infiltrating and three were ductal
      carcinoma in situ (DCIS). Among these 27 lesions, histology was benign at vacuum
      assisted biopsy and at surgery in 19 (70%), cancer at vacuum-assisted biopsy in
      six (22%), atypical ductal hyperplasia at vacuum-assisted biopsy and DCIS at
      surgery in one (4%), and benign at vacuum-assisted biopsy with surgery showing
      microscopic DCIS that was occult at MRI in one (4%). The median time to perform
      vacuum-assisted biopsy of a single lesion was 35 min (mean, 35 min; range, 24-48
      min). Placement of a localizing clip, attempted in 26 lesions, was successful in
      25 (96%) of 26, and the clip was retrieved on specimen radiography in 22 (96%) of
      23. One complication occurred: a hematoma that resolved with compression.
      CONCLUSION: MRI-guided vacuum-assisted biopsy is a fast, safe, and accurate
      alternative to surgical biopsy for breast lesions detected on MRI.

PMID- 14573422
TI  - Accuracy of a collagen-plug biopsy site marking device deployed after
      stereotactic core needle breast biopsy.
AB  - OBJECTIVE: The goal of this study was to compare the accuracy of clip placement
      of a collagen-plug biopsy marking device with that of the more conventional,
      previously evaluated metallic tissue-marking clips. SUBJECTS AND METHODS. The
      placement accuracy of 31 collagen-plug marking devices was compared with the
      placement accuracy of 43 metallic marker clips deployed at biopsies performed
      between August 1, 2002, and November 20, 2002. The precision of marker placement
      was assessed by determining the position of the clip relative to the targeted
      mammographic lesion. Statistical analysis comparing the distance from the clip to
      the targeted lesion was performed. RESULTS: Using a two-group Wilcoxon's rank sum
      test, we found the clip-to-target distances for the collagen-plug central
      titanium marker were significantly different from the clip-to-target distances of
      the conventional metallic marker clips (p = 0.04). There were significantly fewer
      cases in which the clip-to-target distance was 1 cm or greater on at least one
      mammographic projection with the collagen-plug marker (5/31) than with the
      conventional metallic marker clip (19/43) (chi-square test, p = 0.02).
      CONCLUSION: The collagen-plug marking device is an effective alternative to
      existing marker clips, and use of this device may result in fewer cases in which
      the marker clip is substantially displaced (> or = 1 cm) away from the actual
      biopsy site.

PMID- 14573423
TI  - Iatrogenic femoral pseudoaneurysms that are unresponsive to percutaneous thrombin
      injection: potential causes.
AB  - OBJECTIVE: We sought to determine whether any quantitative selection criteria can
      be established to predict which pseudoaneurysms of the common femoral artery will
      fail to respond to thrombin. SUBJECTS AND METHODS. Under sonographic guidance, we
      injected thrombin into 54 consecutive iatrogenic pseudoaneurysms of the common
      femoral artery. We statistically compared the volume, maximum dimension, and neck
      diameter of the pseudoaneurysms and thrombin doses injected into the successfully
      treated (persistent thrombosis on a follow-up duplex sonogram obtained 7-10 days
      after thrombin injection) and unresponsive (sonographically documented recurrence
      within 24 hr) pseudoaneuryms to determine whether any of these factors could help
      to predict a failure to respond to thrombin. For all patients in whom treatment
      failed, findings at surgical repair were noted and sonograms were reviewed to
      confirm the dimensions and appearance of the pseudoaneurysm and the absence of an
      associated arteriovenous fistula. RESULTS: Complete and persistent thrombosis was
      achieved in 49 (91%) of the 54 common femoral artery pseudoaneurysms. In
      comparing the 49 successfully treated patients and the five patients in whom
      treatment failed, we identified no significant differences in the volume, maximum
      dimension, or neck diameter of the pseudoaneurysm (two-sample t test) or in the
      thrombin dose (Wilcoxon's rank sum test). In all five patients with failed
      treatment, an arteriotomy site laceration measuring at least 8.0 mm (n = 4) or
      infection (n = 1) was identified at surgical repair, none of which were
      identifiable even in retrospect on duplex and color Doppler sonography.
      CONCLUSION: Failure of an iatrogenic pseudoaneurysm of the common femoral artery
      to respond to thrombin may indicate an occult vascular injury. In these patients,
      surgical repair, rather than reinjection of thrombin, should be considered.

PMID- 14573424
TI  - Treatment of acute superior mesenteric vein thrombosis with percutaneous
      techniques.

PMID- 14573425
TI  - Is a large fibroid a high-risk factor for uterine artery embolization?
AB  - OBJECTIVE: The objective of our study was to determine whether tumor size,
      specifically uterine fibroids of 10 cm or larger, predisposes a patient to an
      unacceptably high risk at uterine artery embolization. MATERIALS AND METHODS: One
      hundred fifty-two consecutive women underwent embolization for uterine fibroids.
      Complications and outcomes were analyzed using questionnaires and serial MRI
      between women with one or more uterine fibroids of 10 cm or larger diameter
      (mean, 12.4 cm; range, 10-19 cm) (n = 47, group 1) and women with each uterine
      fibroid of less than 10 cm diameter (mean, 6.8 cm; range, 2-9.5 cm) (n = 105,
      group 2). RESULTS: Thirty complications (19.7%, 30/152), which occurred in 27
      women (17.8%, 27/152), were noted. However, 25 of 30 complications were minor,
      requiring no or nominal therapy. They occurred in 19.1% (9/47) of group 1 and in
      15.2% (16/105) of group 2 women (p = 0.637). Major complications requiring major
      therapy, unplanned increased level of care, or unanticipated prolonged
      hospitalization (> 48 hr) or including permanent adverse sequelae were noted in
      6.4% (3/47) of group 1 and in 1.9% (2/105) of group 2 women (p = 0.172). Of these
      five women, four underwent surgery because of sloughing fibroids. Permanent
      adverse sequelae were observed in one woman of group 1, who has had sexual
      dysfunction after embolization. No deaths occurred in either group. There was no
      significant difference in most outcomes or in intervals until the complete
      disappearance of postprocedural pain and full recovery between the two groups.
      CONCLUSION: We found no increased risk to patients undergoing uterine artery
      embolization for fibroids on the basis of tumor size. Successful outcomes can be
      obtained for such lesions.

PMID- 14573426
TI  - Paranephric water instillation: a technique to prevent bowel injury during
      percutaneous renal radiofrequency ablation.

PMID- 14573427
TI  - Prognostic factors for percutaneous microwave coagulation therapy of hepatic
      metastases.
AB  - OBJECTIVE: Microwave-induced tissue coagulation is a new approach for the local
      ablation of hepatic metastases. The purposes of the study were to analyze
      therapeutic results and those influencing factors that might be used to predict
      survival after percutaneous microwave coagulation therapy. SUBJECTS AND METHODS.
      From July 1995 to March 2002, 74 patients with 149 hepatic metastases were
      treated with percutaneous microwave coagulation therapy under sonographic
      guidance. The largest metastasis in each patient ranged from 0.7 to 6.8 cm (mean,
      3.12 cm; SD, 1.81 cm). Survival rates and influencing factors were analyzed.
      RESULTS: The cumulative survival rates of all 74 patients were 91.4% at 1 year,
      59.5% at 2 years, 46.4% at 3 years, 29% at 4 years, and 29% at 5 years. Patient
      age (p = 0.46) and sex (p = 0.12) and site of primary malignancies (p = 0.58)
      were not related to prognosis, whereas tumor grade (p = 0.01), number of
      metastases (p = 0.00), tumor size (p = 0.03), and local recurrence or new
      metastasis (p = 0.00) significantly affected survival as single independent
      factors. Multivariate analysis revealed that tumor grade (p = 0.03), number of
      metastases (p = 0.025), and local recurrence or new metastasis (p = 0.04) each
      had a significant effect on survival. No severe complications occurred.
      CONCLUSION: The probability of long-term survival for patients with one or two
      metastases, well-differentiated tumors, and without recurrence or new metastasis
      may be significantly higher than for other patients.

PMID- 14573430
TI  - Using superparamagnetic iron oxide-enhanced MRI to differentiate metastatic
      hepatic tumors and nonsolid benign lesions.
AB  - OBJECTIVE: We evaluated the ability of superparamagnetic iron oxide (SPIO)
      enhanced MRI to differentiate solid metastatic tumors and nonsolid benign lesions
      by clarifying the characteristic signal-intensity pattern of each lesion on SPIO
      enhanced T2-weighted and heavily T1-weighted gradient-echo images. MATERIALS AND
      METHODS: SPIO-enhanced MRI was performed using a 1.5-T system in 33 consecutive
      patients without cirrhosis who had 81 focal hepatic lesions (42 cysts, 13
      hemangiomas, 26 metastatic tumors). The relative signal intensity of lesions on
      SPIO-enhanced heavily T1- and T2-weighted gradient-echo images was classified
      into one of the following three categories: high intensity, isointensity, or low
      intensity relative to the surrounding liver parenchyma. The diagnostic accuracy
      for differentiating solid metastatic tumors from nonsolid benign lesions (cysts
      or hemangiomas) was determined. RESULTS: A combination of the relative signal
      intensity of the lesion on T2- and heavily T1-weighted gradient-echo images could
      be classified into the following five categories: high intensity and high
      intensity (category 1), high intensity and isointensity (category 2), high
      intensity and low intensity (category 3), isointensity and isointensity (category
      4), and isointensity and low intensity (category 5). According to these
      categories, category 1 contained two hemangiomas, category 2 had 11 hemangiomas,
      category 3 had 25 metastatic tumors and two cysts, category 4 had three cysts,
      and category 5 had 37 cysts and one metastatic tumor. When a tumor with a
      relative signal intensity of categories 1 or 2 was considered to be a hemangioma
      (category 3 metastatic tumors and categories 4 and 5 cysts), diagnostic accuracy
      for characterizing such hepatic lesions was 96% (78/81). CONCLUSION: When
      evaluating metastatic liver tumors on SPIO-enhanced MRI, we recommend that
      heavily T1- and T2-weighted gradient-echo images be obtained with our parameters
      to exclude hemangiomas or cysts.

PMID- 14573429
TI  - Interventional radiology for advanced hepatocellular carcinoma: comparison of
      hepatic artery infusion chemotherapy and transcatheter arterial lipiodol
      chemoembolization.
AB  - OBJECTIVE: The prognosis of advanced hepatocellular carcinoma remains poor. The
      aim of this study was to compare the efficacy of hepatic artery infusion
      chemotherapy and transcatheter arterial Lipiodol chemoembolization for treatment
      of advanced tumor. SUBJECTS AND METHODS. Thirty-seven patients with
      hepatocellular carcinoma and unresectable tumors were enrolled. In the hepatic
      artery infusion chemotherapy group (n = 16), cisplatin (10 mg/person, on days 1
      5) and subsequent 5-fluorouracil (250 mg/person, on days 1-5) were administered
      for four serial courses. In the transcatheter arterial Lipiodol chemoembolization
      group (n = 21), an emulsion of Epirubicin (20-30 mg/person) and Lipiodol was
      administered every 3-4 weeks. RESULTS: The tumor response rates (complete
      response plus partial response for all cases) of the hepatic artery infusion
      chemotherapy and transcatheter arterial Lipiodol chemoembolization groups were
      56.3% and 23.8%, respectively, showing the significantly higher rate in the
      former than in the latter group. The cumulative survival rates between the two
      groups were not significantly different; whereas in those patients whose tumors
      were classified as TNM stage IV or as having the maximal tumor size of greater
      than 5 cm, patients tended to have higher survival rates in the hepatic artery
      infusion chemotherapy group than in the transcatheter arterial Lipiodol
      chemoembolization group. Univariate analysis identified the serum aspartate
      aminotransferase value as solely significant. Patients' adverse reactions were
      successfully managed by treatment of symptoms. Adverse events, such as
      obstructions of the catheter or hepatic artery or infection around the catheter,
      rarely occurred. CONCLUSION: Hepatic artery infusion chemotherapy had a better
      antitumor effect than transcatheter arterial Lipiodol chemoembolization and may
      be a useful therapeutic option for more advanced hepatocellular carcinoma.

PMID- 14573431
TI  - Comparison of conventional sonography, real-time compound sonography, tissue
      harmonic sonography, and tissue harmonic compound sonography of abdominal and
      pelvic lesions.
AB  - OBJECTIVE: The purpose of this study was to compare conventional sonography, real
      time spatial compound sonography, tissue harmonic sonography, and tissue harmonic
      sonography merged with compound sonography for overall image quality, lesion
      conspicuity, and elimination of artifacts. SUBJECTS AND METHODS. In this study,
      150 lesions in 122 randomly selected patients with various abdominal and pelvic
      lesions were evaluated. For each lesion, sonograms were obtained with four
      techniques: conventional sonography, real-time spatial compound sonography,
      tissue harmonic sonography, and tissue harmonic compound sonography. All images
      were reviewed and graded independently by two observers for overall image
      quality, lesion conspicuity, and elimination of artifacts. RESULTS: Statistical
      analysis showed that for overall image quality, lesion conspicuity, and
      elimination of artifacts, tissue harmonic compound sonography was significantly
      superior to all of the other techniques; real-time spatial compound sonography
      was better than tissue harmonic sonography; and conventional sonography was the
      least valuable of all (p < 0.001). When data were analyzed separately according
      to lesion types, tissue harmonic compound sonography was significantly superior
      for revealing stone diseases, liver cysts, gallbladder polyps, and uterine
      myomas. For the remainder of lesion groups, spatial compounding was superior to
      tissue harmonic sonography for all aspects of evaluation, and conventional
      sonography was the least valuable (p < 0.05). CONCLUSION: In abdominal and pelvic
      scanning, tissue harmonic compound sonography provides the best overall image
      quality, best lesion conspicuity, and least artifacts of all the evaluated
      imaging modes. Spatial compound sonography is better than tissue harmonic
      sonography for the evaluation of lesions in general, despite some differences
      among lesion groups.

PMID- 14573432
TI  - Gastrointestinal and genitourinary smooth-muscle tumors.

PMID- 14573434
TI  - Contrast enema before bypass surgery for small-bowel obstruction in the oncologic
      patient: is it necessary?
AB  - OBJECTIVE: We performed a retrospective study to determine the usefulness of
      contrast enema examinations in patients with small-bowel obstruction and known
      intraabdominal malignancy. MATERIALS AND METHODS: Thirty-two patients with known
      or suspected intraabdominal malignancy and small-bowel obstruction who underwent
      both CT and subsequent contrast enema were identified. CT and contrast enema
      reports were reviewed for patients with tumor involvement of the colon to
      determine whether the contrast enema findings had provided additional information
      to the data that had been acquired with CT. In cases in which the contrast enema
      had provided additional information, the patients' medical records were reviewed
      to determine whether treatment had been modified as a result of the additional
      information. RESULTS: In 14 (44%) of 32 patients, the contrast enema provided
      evidence of synchronous colonic disease not previously detected. The colonic
      involvement could be classified into two categories: implants (n = 1) and
      narrowing or complete obstruction (n = 13). Findings of the contrast enema
      resulted in a change in treatment in 10 (32%) of 32 of our patient population.
      CONCLUSION: Patients with known intraabdominal malignancy who present with small
      bowel obstruction may have synchronous large-bowel disease that is undetectable
      on standard CT scans. In these patients, the additional information provided by
      the contrast enema altered subsequent treatment.

PMID- 14573433
TI  - Comparison of CT and sonography in the diagnosis of acute appendicitis: a blinded
      prospective study.
AB  - OBJECTIVE: Our objective was to compare the accuracy of CT and sonography in a
      general community teaching hospital for the diagnosis of acute appendicitis in
      patients with suspected acute appendicitis. SUBJECTS AND METHODS. In this
      prospective study, 199 consecutive patients with clinical signs and symptoms of
      acute appendicitis were examined with sonography (graded compression technique)
      and CT (focused unenhanced single-detector helical CT [5-mm section thickness].
      CT was performed from the L2 vertebral body to the pubic symphysis, and no
      patients were given oral, rectal, or IV contrast medium. The primary sonographic
      criterion for diagnosing acute appendicitis was an incompressible appendix with a
      transverse outer diameter of 6 mm or larger with incompressible periappendicular
      inflamed fat with or without an appendicolith. The primary CT criterion for
      diagnosing acute appendicitis was the identification of an appendix with a
      transverse outer diameter of 6 mm or larger with associated periappendiceal
      inflammatory changes. The results, independently reported, were correlated with
      surgical and histopathologic findings. RESULTS: One hundred thirty-two patients
      had acute appendicitis at surgery, and 67 patients did not. The sensitivity of CT
      and sonography was 76% and 79%, respectively; the specificity was 83% and 78%;
      the accuracy was 78% and 78%; the positive predictive value was 90% and 87%; and
      the negative predictive value was 64% and 65%. CONCLUSION: Unenhanced focused
      single-detector helical CT and graded compression sonography performed in a
      general community teaching hospital by both body imaging radiologists and general
      radiology staff members have a similar accuracy for the diagnosis of acute
      appendicitis.

PMID- 14573435
TI  - Using radiography to reveal chronic jejunal ischemia as a complication of gastric
      bypass surgery.

PMID- 14573436
TI  - CT and MRI of uterine sarcomas and their mimickers.

PMID- 14573437
TI  - CT of a ruptured pyomyoma.

PMID- 14573439
TI  - Imaging of traumatic bladder perforation that spontaneously sealed after omental
      herniation.

PMID- 14573440
TI  - MRI of fetal genitourinary anomalies.
AB  - OBJECTIVE: The objective of our study was to show examples of fetal MRI
      evaluations of congenital genitourinary anomalies and to review the embryology in
      relation to the MRI findings. CONCLUSION: MRI was performed on 35 pregnant women
      with sonographic findings that suggested that their fetuses had genitourinary
      anomalies. Oligohydramnios or anhydramnios was identified in 22 of 35 women and
      did not hinder visualization of anomalies. MRI allowed the amniotic fluid and the
      presence, location, and morphology of kidneys and bladder to be assessed in all
      fetuses at any stage of gestation and depicted sufficient anatomic detail for us
      to evaluate the perineum in 27 of 35 pregnancies. Therefore, we found MRI to be
      an excellent technique for revealing the anatomy of genitourinary anomalies in
      the fetus.

PMID- 14573442
TI  - Sonographic diagnosis of biliary atresia in pediatric patients using the
      "triangular cord" sign versus gallbladder length and contraction.
AB  - OBJECTIVE: A retrospective review was performed to evaluate the importance of the
      "triangular cord" sign in comparison with gallbladder length and contraction for
      the diagnosis of biliary atresia in pediatric patients. MATERIALS AND METHODS:
      Fifty-five fasting infants with cholestatic jaundice were examined on sonography.
      The examinations focused on the visualization of the triangular cord sign and
      assessment of gallbladder length and contraction. The diagnosis of neonatal
      hepatitis or of other causes of infantile cholestasis was made if symptom
      resolution occurred during follow-up. RESULTS: A triangular cord sign was found
      in 27 of 29 infants with biliary atresia and in one of 26 infants with neonatal
      hepatitis or other causes of infantile cholestasis. The diagnostic accuracy was
      95%, sensitivity was 93%, and specificity was 96%. The gallbladder was thought to
      be abnormal if it was less than 1.5 cm long, was not detectable, or was
      detectable but had no lumen. The gallbladder was abnormal in 21 of 29 infants
      with biliary atresia, whereas it was abnormal in eight of 26 infants with
      neonatal hepatitis or other causes of infantile cholestasis. The diagnostic
      accuracy was 71%, sensitivity was 72%, and specificity was 69%. The gallbladder
      was detectable on sonography in 13 infants with biliary atresia and 26 infants
      with neonatal hepatitis or other causes of infantile cholestasis. Gallbladder
      contraction was not confirmed in 11 of 13 infants with biliary atresia and seven
      of 26 infants with neonatal hepatitis or other causes of infantile cholestasis.
      The diagnostic accuracy was 77%, sensitivity was 85%, and specificity was 73%.
      CONCLUSION: The triangular cord sign was a more useful sonographic finding for
      diagnosing biliary atresia than gallbladder length and contraction.

PMID- 14573443
TI  - CT of the pediatric esophagus.

PMID- 14573444
TI  - MRI of trapped periosteum in a proximal tibial physeal injury of a pediatric
      patient.

PMID- 14573446
TI  - MR angiography of anomalous branches of the internal carotid artery.

PMID- 14573445
TI  - Cerebral fractional anisotropy score in trauma patients: a new indicator of white
      matter injury after trauma.
AB  - OBJECTIVE: Previous studies evaluating quantitative cerebral white matter
      diffusion anisotropy indexes have shown alteration in patients after trauma. To
      date, no clinically applicable scale exists by which to gauge and test the
      relevance of these findings. We propose the cerebral fractional anisotropy score
      in trauma (C-FAST) as an index of white matter injury, and we correlate C-FAST
      with several predictor and outcome variables. MATERIALS AND METHODS: Fifteen
      patients were randomly selected from the trauma surgery service. Thirty control
      patients were randomly selected from the emergency department. All patients were
      subjected to MRI evaluation, including a diffusion-weighted sequence. Data
      extracted from the record of each subject included Glasgow Coma Scale, revised
      trauma score, Abbreviated Injury Scale, initial head CT results, patient
      disposition, length of hospital stay, and length of stay in intensive care unit.
      Region of interest measurements were made in fractional anisotropy maps in each
      of 12 white matter regions. Univariate statistics and a two-tailed t test were
      performed on the raw fractional anisotropy data. Data were then dichotomized
      using thresholds from univariate statistics. A C-FAST score was devised from the
      dichotomized data. Logistic regression analyses were performed among the C-FAST,
      outcome, and predictor data. RESULTS: Good correlation was noted between the C
      FAST and death, hospital stay greater than 10 days, and intensive care unit stay
      greater than 5 days. Correlation with discharge to rehabilitation facility was
      good when adjusted for age and sex. Glasgow Coma Scale, revised trauma score, and
      Abbreviated Injury Scale show good correlation as predictors of a critical C
      FAST. CONCLUSION: The C-FAST is a promising index derived from MRI diffusion
      fractional anisotropy measurements that shows successful correlation with outcome
      and predictor variables. A larger investigation is needed to verify the validity
      and stability of the correlations.

PMID- 14573447
TI  - Impact of ambient light and window settings on the detectability of catheters on
      soft-copy display of chest radiographs at bedside.
AB  - OBJECTIVE: The aim of this study was to evaluate how ambient light and
      interactive adjustment of density and contrast affect the detection of catheter
      fragments when interpreting bedside chest radiographs on soft-copy displays.
      MATERIALS AND METHODS: A total of 131 catheter fragments were superimposed over
      10 bedside chest radiographs obtained with storage phosphor technology. Images
      were displayed on a clinical intensive care unit viewing station (color cathode
      ray tube monitor, 21 inch [53 cm], 1280 x 1024 matrix) and were independently
      evaluated by five radiologists. The number of catheter fragments per image varied
      between 12 and 14, with an approximately equal distribution in high- and low
      absorption areas. Detectability of catheter fragments was assessed under subdued
      and bright ambient light conditions with and without interactive adjustment of
      window width and level. RESULTS: Under subdued light, the detection rate of
      catheter fragments was significantly higher than under bright light (51.8% vs
      56.6%, p < 0.05). Interactive window setting adjustment significantly increased
      the detection rate from 52.5% to 60.8% (p < 0.05) under subdued light and from
      47.9% to 55.6% (p < 0.05) under bright light. With adjustment of window settings,
      the difference between the detection rates under subdued light (60.8%) and under
      bright light (55.6%) did not reach statistical significance. CONCLUSION:
      Detection of catheters on soft-copy display is significantly decreased by bright
      ambient light, an effect that can be largely compensated for by means of
      interactive adjustment of window settings.

PMID- 14573448
TI  - The fallacy of double-blinded peer review.

PMID- 14573449
TI  - Not impressed.

PMID- 14573450
TI  - Breast imaging and the symptomatic patient: enough with the "diagnostic"
      mammography.

PMID- 14573451
TI  - Mammography and sonography in young symptomatic women.

PMID- 14573452
TI  - Should we biopsy complex cystic renal masses (Bosniak category III)?

PMID- 14573453
TI  - Breast sonographic screening is not ready for prime time.

PMID- 14573454
TI  - The vital role of radiology in the medical school curriculum.

PMID- 14573456
TI  - Detection of pulmonary emboli resulting from ovarian vein thrombosis.

PMID- 14573455
TI  - What is wrong with this picture? Screening mammography.

PMID- 14573457
TI  - A unique case of foreign-body appendicitis.

PMID- 14573458
TI  - MRI of angiosarcoma of the calvaria.

PMID- 14573459
TI  - Unique adrenal gland imaging features in Addison's disease caused by
      paracoccidioidomycosis.

PMID- 14573460
TI  - Why are suppressors of amber mutations so frequent among Escherichia coli K12
      strains?. A plausible explanation for a long-lasting puzzle.

PMID- 14573461
TI  - Recombinogenic effects of DNA-damaging agents are synergistically increased by
      transcription in Saccharomyces cerevisiae. New insights into transcription
      associated recombination.
AB  - Homologous recombination of a particular DNA sequence is strongly stimulated by
      transcription, a phenomenon observed from bacteria to mammals, which we refer to
      as transcription-associated recombination (TAR). TAR might be an accidental
      feature of DNA chemistry with important consequences for genetic stability.
      However, it is also essential for developmentally regulated processes such as
      class switching of immunoglobulin genes. Consequently, it is likely that TAR
      embraces more than one mechanism. In this study we tested the possibility that
      transcription induces recombination by making DNA more susceptible to
      recombinogenic DNA damage. Using different plasmid-chromosome and direct-repeat
      recombination constructs in which transcription is driven from either the P(GAL1)
      or the P(tet)-regulated promoters, we have shown that either 4-nitroquinoline-N
      oxide (4-NQO) or methyl methanesulfonate (MMS) produces a synergistic increase of
      recombination when combined with transcription. 4-NQO and MMS stimulated
      recombination of a transcriptionally active DNA sequence up to 12,800- and 130
      fold above the spontaneous levels observed in the absence of transcription,
      whereas 4-NQO and MMS alone increased recombination 193- and 4.5-fold,
      respectively. Our results provide evidence that TAR is due, at least in part, to
      the ability of transcription to enhance the accessibility of DNA to exogenous
      chemicals and internal metabolites responsible for recombinogenic lesions. We
      discuss possible parallelisms between the mechanisms of induction of
      recombination and mutation by transcription.

PMID- 14573462
TI  - The G1 cyclin Cln3p controls vacuolar biogenesis in Saccharomyces cerevisiae.
AB  - How organelle biogenesis and inheritance is linked to cell division is poorly
      understood. In the budding yeast Saccharomyces cerevisiae the G(1) cyclins
      Cln1,2,3p control initiation of cell division. Here we show that Cln3p controls
      vacuolar (lysosomal) biogenesis and segregation. First, loss of Cln3p, but not
      Cln1p or Cln2p, resulted in vacuolar fragmentation. Although the vacuoles of
      cln3delta cells were fragmented, together they occupied a large space, which
      accounted for a significant fraction of the overall cell size increase in
      cln3delta cells. Second, cytosol prepared from cells lacking Cln3p had reduced
      vacuolar homotypic fusion activity in cell-free assays. Third, vacuolar
      segregation was perturbed in cln3delta cells. Our findings reveal a novel role
      for a eukaryotic G(1) cyclin in cytoplasmic organelle biogenesis and segregation.

PMID- 14573463
TI  - Schizosaccharomyces pombe Ras1 effector, Scd1, interacts with Klp5 and Klp6
      kinesins to mediate cytokinesis.
AB  - Fission yeast Scd1 is an exchange factor for Cdc42 and an effector of Ras1. In a
      screen for scd1 interacting genes, we isolated klp5 and klp6, which encode
      presumptive kinesins. Klp5 and Klp6 form a complex to control the same processes,
      which so far include microtubule dynamics and chromosome segregation. We showed
      that klp5 or klp6 inactivation in combination with the scd1 deletion (scd1delta)
      created a synthetic temperature-dependent growth defect. Further genetic analysis
      demonstrated that Klp5 and Klp6 interacted specifically with the Ras1-Scd1
      pathway, but not with the Ras1-Byr2 pathway. In addition, Klp5 and Klp6 can
      stably associate with Scd1 and Cdc42. A deletion in the Scd1 C terminus, which
      contains the PB1 domain, prevented Scd1 binding to Klp5/6 and caused a growth
      defect in Klp5/6 mutant cells that is indistinguishable from that induced by
      scd1delta. Analysis of the double-mutant phenotype indicated that at the
      nonpermissive temperature, cells failed to undergo cytokinesis efficiently. These
      cells contained abnormal contractile rings in which F-actin and Mid1, a key
      regulator of F-actin ring formation and positioning, are mispositioned and
      fragmented. These data suggest that Klp5/6 cooperate with the Ras1-Scd1 pathway
      to influence proper formation of the contractile ring for cytokinesis.

PMID- 14573464
TI  - The role of Cdh1p in maintaining genomic stability in budding yeast.
AB  - Cdh1p, a substrate specificity factor for the cell cycle-regulated ubiquitin
      ligase, the anaphase-promoting complex/cyclosome (APC/C), promotes exit from
      mitosis by directing the degradation of a number of proteins, including the
      mitotic cyclins. Here we present evidence that Cdh1p activity at the M/G(1)
      transition is important not only for mitotic exit but also for high-fidelity
      chromosome segregation in the subsequent cell cycle. CDH1 showed genetic
      interactions with MAD2 and PDS1, genes encoding components of the mitotic spindle
      assembly checkpoint that acts at metaphase to prevent premature chromosome
      segregation. Unlike cdh1delta and mad2delta single mutants, the mad2delta
      cdh1delta double mutant grew slowly and exhibited high rates of chromosome and
      plasmid loss. Simultaneous deletion of PDS1 and CDH1 caused extensive chromosome
      missegregation and cell death. Our data suggest that at least part of the
      chromosome loss can be attributed to kinetochore/spindle problems. Our data
      further suggest that Cdh1p and Sic1p, a Cdc28p/Clb inhibitor, have overlapping as
      well as nonoverlapping roles in ensuring proper chromosome segregation. The
      severe growth defects of both mad2delta cdh1delta and pds1delta cdh1dDelta
      strains were rescued by overexpressing Swe1p, a G(2)/M inhibitor of the cyclin
      dependent kinase, Cdc28p/Clb. We propose that the failure to degrade cyclins at
      the end of mitosis leaves cdh1delta mutant strains with abnormal Cdc28p/Clb
      activity that interferes with proper chromosome segregation.

PMID- 14573465
TI  - Fission yeast Tup1-like repressors repress chromatin remodeling at the fbp1+
      promoter and the ade6-M26 recombination hotspot.
AB  - Chromatin remodeling plays crucial roles in the regulation of gene expression and
      recombination. Transcription of the fission yeast fbp1(+) gene and recombination
      at the meiotic recombination hotspot ade6-M26 (M26) are both regulated by cAMP
      responsive element (CRE)-like sequences and the CREB/ATF-type transcription
      factor Atf1*Pcr1. The Tup11 and Tup12 proteins, the fission yeast counterparts of
      the Saccharomyces cerevisiae Tup1 corepressor, are involved in glucose repression
      of the fbp1(+) transcription. We have analyzed roles of the Tup1-like
      corepressors in chromatin regulation around the fbp1(+) promoter and the M26
      hotspot. We found that the chromatin structure around two regulatory elements for
      fbp1(+) was remodeled under derepressed conditions in concert with the robust
      activation of fbp1(+) transcription. Strains with tup11delta tup12delta double
      deletions grown in repressed conditions exhibited the chromatin state associated
      with wild-type cells grown in derepressed conditions. Interestingly, deletion of
      rst2(+), encoding a transcription factor controlled by the cAMP-dependent kinase,
      alleviated the tup11delta tup12delta defects in chromatin regulation but not in
      transcription repression. The chromatin at the M26 site in mitotic cultures of a
      tup11delta tup12delta mutant resembled that of wild-type meiotic cells. These
      observations suggest that these fission yeast Tup1-like corepressors repress
      chromatin remodeling at CRE-related sequences and that Rst2 antagonizes this
      function.

PMID- 14573466
TI  - Yeast Nap1-binding protein Nbp2p is required for mitotic growth at high
      temperatures and for cell wall integrity.
AB  - Nbp2p is a Nap1-binding protein in Saccharomyces cerevisiae identified by its
      interaction with Nap1 by a two-hybrid system. NBP2 encodes a novel protein
      consisting of 236 amino acids with a Src homology 3 (SH3) domain. We showed that
      NBP2 functions to promote mitotic cell growth at high temperatures and cell wall
      integrity. Loss of Nbp2 results in cell death at high temperatures and in
      sensitivity to calcofluor white. Cell death at high temperature is thought not to
      be due to a weakened cell wall. Additionally, we have isolated several type-2C
      serine threonine protein phosphatases (PTCs) as multicopy suppressors and MAP
      kinase-kinase (MAPKK), related to the yeast PKC MAPK pathway, as deletion
      suppressors of the nbp2Delta mutant. Screening for deletion suppressors is a new
      genetic approach to identify and characterize additional proteins in the Nbp2
      dependent pathway. Genetic analyses suggested that Ptc1, which interacts with
      Nbp2 by the two-hybrid system, acts downstream of Nbp2 and that cells lacking the
      function of Nbp2 prefer to lose Mkk1, but the PKC MAPK pathway itself is
      indispensable when Nbp2 is deleted at high temperature.

PMID- 14573467
TI  - A novel step in beta-tubulin folding is important for heterodimer formation in
      Saccharomyces cerevisiae.
AB  - Undimerized beta-tubulin is toxic in the yeast S. cerevisiae. It can arise if
      levels of beta-tubulin and alpha-tubulin are unbalanced or if the tubulin
      heterodimer dissociates. We are using the toxicity of beta-tubulin to understand
      early steps in microtubule morphogenesis. We find that deletion of PLP1
      suppresses toxic beta-tubulin formed by disparate levels of alpha- and beta
      tubulin. That suppression occurs either when alpha-tubulin is modestly
      underexpressed relative to beta-tubulin or when beta-tubulin is inducibly and
      strongly overexpressed. Plp1p does not affect tubulin expression. Instead, a
      significant proportion of the undimerized beta-tubulin in plp1Delta cells is less
      toxic than that in wild-type cells. It is also less able to combine with alpha
      tubulin to form a heterodimer. As a result, plp1Delta cells have lower levels of
      heterodimer. Importantly, plp1Delta cells that also lack Pac10, a component of
      the GimC/PFD complex, are even less affected by free beta-tubulin. Our results
      suggest that Plp1p defines a novel early step in beta-tubulin folding.

PMID- 14573468
TI  - The Aspergillus nidulans swoC1 mutant shows defects in growth and development.
AB  - Previous work identified swoC1 as a single-gene mutant with defects in polarity
      establishment. In this study swoC1 was shown to have defects in endocytosis,
      compartmentation, nuclear distribution, and conidiation. Temperature-shift
      experiments showed that the swoC1 mutant establishes multiple random sites of
      germ tube emergence. Surprisingly, these experiments also showed that even a
      slight delay in polarity establishment causes defects in later vegetative growth
      and asexual reproduction. The swoC gene was mapped to the centromere of
      chromosome III and cloned by complementation of the temperature-sensitive
      phenotype. The predicted SwoCp is homologous to rRNA pseudouridine synthases of
      yeast (Cbf5p) and humans (Dkc1p). However, neither rRNA pseudouridine synthesis
      nor rRNA processing appears to be affected in the swoC1 mutant. The swoC1
      mutation occurs in the putative RNA-binding domain upstream of the C terminus,
      leaving the N-terminal TRUB catalytic domain intact. Interestingly, while
      deletion of the swoC gene was lethal in A. nidulans, the C terminus, including
      NLS, microtubule-binding, and coiled-coil domains, was dispensable for growth.
      SwoCp likely plays an important role in polar growth and nuclear distribution in
      A. nidulans, functions not yet described for its homologs.

PMID- 14573470
TI  - The promotion of gonadal cell divisions by the Caenorhabditis elegans TRPM cation
      channel GON-2 is antagonized by GEM-4 copine.
AB  - The initiation of postembryonic cell divisions by the gonadal precursors of C.
      elegans requires the activity of gon-2. gon-2 encodes a predicted cation channel
      (GON-2) of the TRPM subfamily of TRP proteins and is likely to mediate the influx
      of Ca(2+) and/or Mg(2+). We report here that mutations in gem-4 (gon-2 extragenic
      modifier) are capable of suppressing loss-of-function alleles of gon-2. gem-4
      encodes a member of the copine family of Ca(2+)-dependent phosphatidylserine
      binding proteins. Overall, our data indicate that GEM-4 antagonizes GON-2. This
      antagonism could be mediated by a direct inhibition of GON-2 by GEM-4, since both
      proteins are predicted to be localized to the plasma membrane. Alternatively, GEM
      4 could affect GON-2 activity levels by either promoting endocytosis or
      inhibiting exocytosis of vesicles that carry GON-2. It is also possible that GEM
      4 and GON-2 act in parallel to each other. Mutation of gem-4 does not suppress
      the gonadal defects produced by inactivation of gon-4, suggesting that gon-4
      either acts downstream of gem-4 and gon-2 or acts in a parallel regulatory
      pathway.

PMID- 14573469
TI  - Allele frequency-based analyses robustly map sequence sites under balancing
      selection in a malaria vaccine candidate antigen.
AB  - The Plasmodium falciparum apical membrane antigen 1 (AMA1) is a leading candidate
      for a malaria vaccine. Here, within-population analyses of alleles from 50 Thai
      P. falciparum isolates yield significant evidence for balancing selection on
      polymorphisms within the disulfide-bonded domains I and III of the surface
      accessible ectodomain of AMA1, a result very similar to that seen previously in a
      Nigerian population. Studying the frequency of nucleotide polymorphisms in both
      populations shows that the between-population component of variance (F(ST)) is
      significantly lower in domains I and III compared to the intervening domain II
      and compared to 11 unlinked microsatellite loci. A nucleotide site-by-site
      analysis shows that sites with exceptionally high or low F(ST) values cluster
      significantly into serial runs, with four runs of low values in domain I and one
      in domain III. These runs may map the sequences that are consistently under the
      strongest balancing selection from naturally acquired immune responses.

PMID- 14573471
TI  - The evolutionary duplication and probable demise of an endodermal GATA factor in
      Caenorhabditis elegans.
AB  - We describe the elt-4 gene from the nematode Caenorhabditis elegans. elt-4 is
      predicted to encode a very small (72 residues, 8.1 kD) GATA-type zinc finger
      transcription factor. The elt-4 gene is located approximately 5 kb upstream of
      the C. elegans elt-2 gene, which also encodes a GATA-type transcription factor;
      the zinc finger DNA-binding domains are highly conserved (24/25 residues) between
      the two proteins. The elt-2 gene is expressed only in the intestine and is
      essential for normal intestinal development. This article explores whether elt-4
      also has a role in intestinal development. Reporter fusions to the elt-4 promoter
      or reporter insertions into the elt-4 coding regions show that elt-4 is indeed
      expressed in the intestine, beginning at the 1.5-fold stage of embryogenesis and
      continuing into adulthood. elt-4 reporter fusions are also expressed in nine
      cells of the posterior pharynx. Ectopic expression of elt-4 cDNA within the
      embryo does not cause detectable ectopic expression of biochemical markers of gut
      differentiation; furthermore, ectopic elt-4 expression neither inhibits nor
      enhances the ectopic marker expression caused by ectopic elt-2 expression. A
      deletion allele of elt-4 was isolated but no obvious phenotype could be detected,
      either in the gut or elsewhere; brood sizes, hatching efficiencies, and growth
      rates were indistinguishable from wild type. We found no evidence that elt-4
      provided backup functions for elt-2. We used microarray analysis to search for
      genes that might be differentially expressed between L1 larvae of the elt-4
      deletion strain and wild-type worms. Paired hybridizations were repeated seven
      times, allowing us to conclude, with some confidence, that no candidate target
      transcript could be identified as significantly up- or downregulated by loss of
      elt-4 function. In vitro binding experiments could not detect specific binding of
      ELT-4 protein to candidate binding sites (double-stranded oligonucleotides
      containing single or multiple WGATAR sequences); ELT-4 protein neither enhanced
      nor inhibited the strong sequence-specific binding of the ELT-2 protein. Whereas
      ELT-2 protein is a strong transcriptional activator in yeast, ELT-4 protein has
      no such activity under similar conditions, nor does it influence the
      transcriptional activity of coexpressed ELT-2 protein. Although an elt-2 homolog
      was easily identified in the genomic sequence of the related nematode C.
      briggsae, no elt-4 homolog could be identified. Analysis of the changes in silent
      third codon positions within the DNA-binding domains indicates that elt-4 arose
      as a duplication of elt-2, some 25-55 MYA. Thus, elt-4 has survived far longer
      than the average duplicated gene in C. elegans, even though no obvious biological
      function could be detected. elt-4 provides an interesting example of a tandemly
      duplicated gene that may originally have been the same size as elt-2 but has
      gradually been whittled down to its present size of little more than a zinc
      finger. Although elt-4 must confer (or must have conferred) some selective
      advantage to C. elegans, we suggest that its ultimate evolutionary fate will be
      disappearance from the C. elegans genome.

PMID- 14573472
TI  - Dominance and overdominance of mildly deleterious induced mutations for fitness
      traits in Caenorhabditis elegans.
AB  - We estimated the average dominance coefficient of mildly deleterious mutations
      (h, the proportion by which mutations in the heterozygous state reduce fitness
      components relative to those in the homozygous state) in the nematode
      Caenorhabditis elegans. From 56 worm lines that carry mutations induced by the
      point mutagen ethyl methanesulfonate (EMS), we selected 19 lines that are
      relatively high in fitness and estimated the viabilities, productivities, and
      relative fitnesses of heterozygotes and homozygotes compared to the ancestral
      wild type. There was very little effect of homozygous or heterozygous mutations
      on egg-to-adult viability. For productivity and relative fitness, we found that
      the average dominance coefficient, h, was approximately 0.1, suggesting that
      mildly deleterious mutations are on average partially recessive. These estimates
      were not significantly different from zero (complete recessivity) but were
      significantly different from 0.5 (additivity). In addition, there was a
      significant amount of variation in h among lines, and analysis of average
      dominance coefficients of individual lines suggested that several lines showed
      overdominance for fitness. Further investigation of two of these lines partially
      confirmed this finding.

PMID- 14573473
TI  - Mutations in eukaryotic release factors 1 and 3 act as general nonsense
      suppressors in Drosophila.
AB  - In a screen for suppressors of the Drosophila wingless(PE4) nonsense allele, we
      isolated mutations in the two components that form eukaryotic release factor.
      eRF1 and eRF3 comprise the translation termination complex that recognizes stop
      codons and catalyzes the release of nascent polypeptide chains from ribosomes.
      Mutations disrupting the Drosophila eRF1 and eRF3 show a strong maternal-effect
      nonsense suppression due to readthrough of stop codons and are zygotically lethal
      during larval stages. We tested nonsense mutations in wg and in other
      embryonically acting genes and found that different stop codons can be suppressed
      but only a subset of nonsense alleles are subject to suppression. We suspect that
      the context of the stop codon is significant: nonsense alleles sensitive to
      suppression by eRF1 and eRF3 encode stop codons that are immediately followed by
      a cytidine. Such suppressible alleles appear to be intrinsically weak, with a low
      level of readthrough that is enhanced when translation termination is disrupted.
      Thus the eRF1 and eRF3 mutations provide a tool for identifying nonsense alleles
      that are leaky. Our findings have important implications for assigning null
      mutant phenotypes and for selecting appropriate alleles to use in suppressor
      screens.

PMID- 14573474
TI  - A family of genes clustered at the Triplo-lethal locus of Drosophila melanogaster
      has an unusual evolutionary history and significant synteny with Anopheles
      gambiae.
AB  - Within the unique Triplo-lethal region (Tpl) of the Drosophila melanogaster
      genome we have found a cluster of 20 genes encoding a novel family of proteins.
      This family is also present in the Anopheles gambiae genome and displays
      remarkable synteny and sequence conservation with the Drosophila cluster. The
      family is also present in the sequenced genome of D. pseudoobscura, and homologs
      have been found in Aedes aegypti mosquitoes and in four other insect orders, but
      it is not present in the sequenced genome of any noninsect species. Phylogenetic
      analysis suggests that the cluster evolved prior to the divergence of Drosophila
      and Anopheles (250 MYA) and has been highly conserved since. The ratio of
      synonymous to nonsynonymous substitutions and the high codon bias suggest that
      there has been selection on this family both for expression level and function.
      We hypothesize that this gene family is Tpl, name it the Osiris family, and
      consider possible functions. We also predict that this family of proteins, due to
      the unique dosage sensitivity and the lack of homologs in noninsect species,
      would be a good target for genetic engineering or novel insecticides.

PMID- 14573475
TI  - Mapping determinants of variation in energy metabolism, respiration and flight in
      Drosophila.
AB  - We employed quantitative trait locus (QTL) mapping to dissect the genetic
      architecture of a hierarchy of functionally related physiological traits,
      including metabolic enzyme activity, metabolite storage, metabolic rate, and free
      flight performance in recombinant inbred lines of Drosophila melanogaster. We
      identified QTL underlying variation in glycogen synthase, hexokinase,
      phosphoglucomutase, and trehalase activity. In each case variation mapped away
      from the enzyme-encoding loci, indicating that trans-acting regions of the genome
      are important sources of variation within the metabolic network. Individual QTL
      associated with variation in metabolic rate and flight performance explained
      between 9 and 35% of the phenotypic variance. Bayesian QTL analysis identified
      epistatic effects underlying variation in flight velocity, metabolic rate,
      glycogen content, and several metabolic enzyme activities. A region on the third
      chromosome was associated with expression of the glucose-6-phosphate branchpoint
      enzymes and with metabolic rate and flight performance. These genomic regions are
      of special interest as they may coordinately regulate components of energy
      metabolism with effects on whole-organism physiological performance. The complex
      biochemical network is encoded by an equally complex network of interacting
      genetic elements with potentially pleiotropic effects. This has important
      consequences for the evolution of performance traits that depend upon these
      metabolic networks.

PMID- 14573476
TI  - A deficiency screen of the major autosomes identifies a gene (matrimony) that is
      haplo-insufficient for achiasmate segregation in Drosophila oocytes.
AB  - In Drosophila oocytes, euchromatic homolog-homolog associations are released at
      the end of pachytene, while heterochromatic pairings persist until metaphase I. A
      screen of 123 autosomal deficiencies for dominant effects on achiasmate
      chromosome segregation has identified a single gene that is haplo-insufficient
      for homologous achiasmate segregation and whose product may be required for the
      maintenance of such heterochromatic pairings. Of the deficiencies tested, only
      one exhibited a strong dominant effect on achiasmate segregation, inducing both X
      and fourth chromosome nondisjunction in FM7/X females. Five overlapping
      deficiencies showed a similar dominant effect on achiasmate chromosome
      disjunction and mapped the haplo-insufficient meiotic gene to a small interval
      within 66C7-12. A P-element insertion mutation in this interval exhibits a
      similar dominant effect on achiasmate segregation, inducing both high levels of X
      and fourth chromosome nondisjunction in FM7/X females and high levels of fourth
      chromosome nondisjunction in X/X females. The insertion site for this P element
      lies immediately upstream of CG18543, and germline expression of a UAS-CG18543
      cDNA construct driven by nanos-GAL4 fully rescues the dominant meiotic defect. We
      conclude that CG18543 is the haplo-insufficient gene and have renamed this gene
      matrimony (mtrm). Cytological studies of prometaphase and metaphase I in mtrm
      hemizygotes demonstrate that achiasmate chromosomes are not properly positioned
      with respect to their homolog on the meiotic spindle. One possible, albeit
      speculative, interpretation of these data is that the presence of only a single
      copy of mtrm disrupts the function of whatever "glue" holds heterochromatically
      paired homologs together from the end of pachytene until metaphase I.

PMID- 14573477
TI  - Genetic analysis of the ADGF multigene family by homologous recombination and
      gene conversion in Drosophila.
AB  - Many Drosophila genes exist as members of multigene families and within each
      family the members can be functionally redundant, making it difficult to identify
      them by classical mutagenesis techniques based on phenotypic screening. We have
      addressed this problem in a genetic analysis of a novel family of six adenosine
      deaminase-related growth factors (ADGFs). We used ends-in targeting to introduce
      mutations into five of the six ADGF genes, taking advantage of the fact that five
      of the family members are encoded by a three-gene cluster and a two-gene cluster.
      We used two targeting constructs to introduce loss-of-function mutations into all
      five genes, as well as to isolate different combinations of multiple mutations,
      independent of phenotypic consequences. The results show that (1) it is possible
      to use ends-in targeting to disrupt gene clusters; (2) gene conversion, which is
      usually considered a complication in gene targeting, can be used to help recover
      different mutant combinations in a single screening procedure; (3) the reduction
      of duplication to a single copy by induction of a double-strand break is better
      explained by the single-strand annealing mechanism than by simple crossing over
      between repeats; and (4) loss of function of the most abundantly expressed family
      member (ADGF-A) leads to disintegration of the fat body and the development of
      melanotic tumors in mutant larvae.

PMID- 14573478
TI  - Testing for asymmetrical gene flow in a Drosophila melanogaster body-size cline.
AB  - Asymmetrical gene flow is an important, but rarely examined genetic parameter.
      Here, we develop a new method for detecting departures from symmetrical migration
      between two populations using microsatellite data that are based on the
      difference in the proportion of private alleles. Application of this approach to
      data collected from wild-caught Drosophila melanogaster along a latitudinal body
      size cline in eastern Australia revealed that asymmetrical gene flow could be
      detected, but was uncommon, nonlocalized, and occurred in both directions. We
      also show that, in contrast to the findings of a previous study, there is good
      evidence to suggest that the cline experiences significant levels of gene flow
      between populations.

PMID- 14573479
TI  - R1 and R2 retrotransposition and deletion in the rDNA loci on the X and Y
      chromosomes of Drosophila melanogaster.
AB  - The non-LTR retrotransposons R1 and R2 insert into the 28S rRNA genes of
      arthropods. Comparisons among Drosophila lineages have shown that these elements
      are vertically inherited, while studies within species have indicated a rapid
      turnover of individual copies (elimination of old copies and the insertion of new
      copies). To better understand the turnover of R1 and R2, 200 retrotranspositions
      and nearly 100 eliminations have been scored in the Harwich mutation-accumulation
      lines of Drosophila melanogaster. Because the rDNA arrays in D. melanogaster are
      present on the X and Y chromosomes and no exchanges were detected in these lines,
      it was possible to show that R1 retrotranspositions occur predominantly in the
      male germ line, while R2 retrotranspositions were more evenly divided between the
      germ lines of both sexes. The rate of elimination of elements from the Y rDNA
      array was twice that of the X rDNA array with both chromosomal loci containing
      regions where the rate of elimination was on average eight times higher. Most R1
      and R2 eliminations appear to occur by large intrachromosomal events (i.e., loop
      out events) that involve multiple rDNA units. These findings are interpreted in
      light of the known abundance of R1 and R2 elements in the X and Y rDNA loci of D.
      melanogaster.

PMID- 14573480
TI  - An AFLP-based genetic linkage map of channel catfish (Ictalurus punctatus)
      constructed by using an interspecific hybrid resource family.
AB  - Catfish is the major aquaculture species in the United States. The hybrid catfish
      produced by crossing channel catfish females with blue catfish males exhibit a
      number of desirable production traits, but their mass production has been
      difficult. To introduce desirable genes from blue catfish into channel catfish
      through introgression, a genetic linkage map is helpful. In this project, a
      genetic linkage map was constructed using amplified fragment length polymorphism
      (AFLP). A total of 607 AFLP markers were analyzed using 65 primer combinations
      and an interspecific backcross resource family. A total of 418 AFLP markers were
      assigned to 44 linkage groups. Among the remaining 189 markers, 101 were not used
      because of significant segregation distortion, 29 were unlinked, and 59 were
      eliminated because they span very large distances. The 418 AFLP markers covered
      1593 cM Kosambi. The AFLP markers showed a high level of clustering that appears
      to be related to certain primer combinations. This linkage map will serve as the
      basis for mapping a greater number of markers to provide a map with high enough
      resolution for it to be useful for selective breeding programs using
      introgression.

PMID- 14573482
TI  - Limitations of allotopic expression of mitochondrial genes in mammalian cells.
AB  - The possibility of expressing mitochondrial DNA-coded genes in the nuclear
      cytoplasmic compartment provides an attractive system for genetic treatment of
      mitochondrial disorders associated with mitochondrial DNA mutations. In theory,
      by recoding mitochondrial genes to adapt them to the universal genetic code and
      by adding a DNA sequence coding for a mitochondrial-targeting sequence, one could
      achieve correct localization of the gene product. Such transfer has occurred in
      nature, and certain species of algae and plants express a number of polypeptides
      that are commonly coded by mtDNA in the nuclear-cytoplasmic compartment. In the
      present study, allotopic expression of three different mtDNA-coded polypeptides
      (ATPase8, apocytochrome b, and ND4) into COS-7 and HeLa cells was analyzed. Among
      these, only ATPase8 was correctly expressed and localized to mitochondria. The
      full-length, as well as truncated forms, of apocytochrome b and ND4 decorated the
      periphery of mitochondria, but also aggregated in fiber-like structures
      containing tubulin and in some cases also vimentin. The addition of a hydrophilic
      tail (EGFP) to the C terminus of these polypeptides did not change their
      localization. Overexpression of molecular chaperones also did not have a
      significant effect in preventing aggregations. Allotopic expression of
      apocytochrome b and ND4 induced a loss of mitochondrial membrane potential in
      transfected cells, which can lead to cell death. Our observations suggest that
      only a subset of mitochondrial genes can be replaced allotopically. Analyses of
      the hydrophobic patterns of different polypeptides suggest that hydrophobicity of
      the N-terminal segment is the main determinant for the importability of peptides
      into mammalian mitochondria.

PMID- 14573481
TI  - Likelihood models of somatic mutation and codon substitution in cancer genes.
AB  - The role of somatic mutation in cancer is well established and several genes have
      been identified that are frequent targets. This has enabled large-scale screening
      studies of the spectrum of somatic mutations in cancers of particular organs.
      Cancer gene mutation databases compile the results of many studies and can
      provide insight into the importance of specific amino acid sequences and
      functional domains in cancer, as well as elucidate aspects of the mutation
      process. Past studies of the spectrum of cancer mutations (in particular genes)
      have examined overall frequencies of mutation (at specific nucleotides) and of
      missense, nonsense, and silent substitution (at specific codons) both in the
      sequence as a whole and in a specific functional domain. Existing methods ignore
      features of the genetic code that allow some codons to mutate to missense, or
      stop, codons more readily than others (i.e., by one nucleotide change, vs. two or
      three). A new codon-based method to estimate the relative rate of substitution
      (fixation of a somatic mutation in a cancer cell lineage) of nonsense vs.
      missense mutations in different functional domains and in different tumor tissues
      is presented. Models that account for several potential influences on rates of
      somatic mutation and substitution in cancer progenitor cells and allow biases of
      mutation rates for particular dinucleotide sequences (CGs and dipyrimidines),
      transition vs. transversion bias, and variable rates of silent substitution
      across functional domains (useful in detecting investigator sampling bias) are
      considered. Likelihood-ratio tests are used to choose among models, using cancer
      gene mutation data. The method is applied to analyze published data on the
      spectrum of p53 mutations in cancers. A novel finding is that the ratio of the
      probability of nonsense to missense substitution is much lower in the DNA-binding
      and transactivation domains (ratios near 1) than in structural domains such as
      the linker, tetramerization (oligomerization), and proline-rich domains (ratios
      exceeding 100 in some tissues), implying that the specific amino acid sequence
      may be less critical in structural domains (e.g., amino acid changes less often
      lead to cancer). The transition vs. transversion bias and effect of CpG
      dinucleotides on mutation rates in p53 varied greatly across cancers of different
      organs, likely reflecting effects of different endogenous and exogenous factors
      influencing mutation in specific organs.

PMID- 14573483
TI  - A small deletion hotspot in the type II keratin gene mK6irs1/Krt2-6g on mouse
      chromosome 15, a candidate for causing the wavy hair of the caracul (Ca)
      mutation.
AB  - A new mutation has arisen in a colony of mice transgenic for human alpha
      galactosidase. The mutation is independent of the transgenic insertion, autosomal
      dominant, and morphologically very similar to the classical wavy coat mutation,
      caracul (Ca), on chromosome 15. Therefore, we designated this locus the caracul
      Rinshoken (Ca(Rin)). Applying a positional cloning approach, we identified the
      mK6irs1/Krt2-6g gene as a strong candidate for Ca(Rin) because among five Ca
      alleles examined mutations always occurred in the highly conserved positions of
      the alpha-helical rod domain (1A and 2B subdomain) of this putative gene product.
      The most striking finding is that four independently discovered alleles, the
      three preexistent alleles Ca(J), Ca(9J), Ca(10J), and our allele Ca(Rin), all
      share one identical amino acid deletion (N 140 del) and the fifth, Ca(medJ), has
      an amino acid substitution (A 431 D). These findings indicate that a mutation
      hotspot exists in the Ca locus. Additionally, we describe a Ca mutant allele
      induced by ENU mutagenesis, which also possesses an amino acid substitution (L
      424 W) in the mK6irs1/Krt2-6g gene. The identification of the Ca candidate gene
      enables us to further define the nature of the genetic pathway required for hair
      formation and provides an important new candidate that may be implicated in human
      hair and skin diseases.

PMID- 14573484
TI  - Likelihood analysis of asymmetrical mutation bias gradients in vertebrate
      mitochondrial genomes.
AB  - Protein-coding genes in mitochondrial genomes have varying degrees of asymmetric
      skew in base frequencies at the third codon position. The variation in skew among
      genes appears to be caused by varying durations of time that the heavy strand
      spends in the mutagenic single-strand state during replication (D(ssH)). The
      primary data used to study skew have been the gene-by-gene base frequencies in
      individual taxa, which provide little information on exactly what kinds of
      mutations are responsible for the base frequency skew. To assess the contribution
      of individual mutation components to the ancestral vertebrate substitution
      pattern, here we analyze a large data set of complete vertebrate mitochondrial
      genomes in a phylogeny-based likelihood context. This also allows us to evaluate
      the change in skew continuously along the mitochondrial genome and to directly
      estimate relative substitution rates. Our results indicate that different types
      of mutation respond differently to the D(ssH) gradient. A primary role for
      hydrolytic deamination of cytosines in creating variance in skew among genes was
      not supported, but rather linearly increasing rates of mutation from adenine to
      hypoxanthine with D(ssH) appear to drive regional differences in skew.
      Substitutions due to hydrolytic deamination of cytosines, although common, appear
      to quickly saturate, possibly due to stabilization by the mitochondrial DNA
      single-strand-binding protein. These results should form the basis of more
      realistic models of DNA and protein evolution in mitochondria.

PMID- 14573485
TI  - Mixed-model reanalysis of primate data suggests tissue and species biases in
      oligonucleotide-based gene expression profiles.
AB  - An emerging issue in evolutionary genetics is whether it is possible to use gene
      expression profiling to identify genes that are associated with morphological,
      physiological, or behavioral divergence between species and whether these genes
      have undergone positive selection. Some of these questions were addressed in a
      recent study (Enard et al. 2002) of the difference in gene expression among
      human, chimp, and orangutan, which suggested an accelerated rate of divergence in
      gene expression in the human brain relative to liver. Reanalysis of the
      Affymetrix data set using analysis of variance methods to quantify the
      contributions of individuals and species to variation in expression of 12,600
      genes indicates that as much as one-quarter of the genome shows divergent
      expression between primate species at the 5% level. The magnitude of fold change
      ranges from 1.2-fold up to 8-fold. Similar conclusions apply to reanalysis of
      Enard et al. 2002 parallel murine data set. However, biases inherent to short
      oligonucleotide microarray technology may account for some of the tissue and
      species effects. At high significance levels, more differences were observed in
      the liver than in the brain in each of the pairwise species comparisons, so it is
      not clear that expression divergence is accelerated in the human brain. Further,
      there is an apparent bias toward upregulation of gene expression in the brain in
      both primates and mice, whereas genes are equally likely to be up- or
      downregulated in the liver when these species diverge. A small subset of genes
      that are candidates for adaptive divergence may be identified on the basis of a
      high ratio of interspecific to intraspecific divergence.

PMID- 14573486
TI  - Population structure and its effect on haplotype diversity and linkage
      disequilibrium surrounding the xa5 locus of rice (Oryza sativa L.).
AB  - To assess the usefulness of linkage disequilibrium mapping in an autogamous,
      domesticated species, we have characterized linkage disequilibrium in the
      candidate region for xa5, a recessive gene conferring race-specific resistance to
      bacterial blight in rice. This trait and locus have good mapping information, a
      tractable phenotype, and available sequence data, but no cloned gene. We sampled
      13 short segments from the 70-kb candidate region in 114 accessions of Oryza
      sativa. Five additional segments were sequenced from the adjacent 45-kb region in
      resistant accessions to estimate the distance at which linkage disequilibrium
      decays. The data show significant linkage disequilibrium between sites 100 kb
      apart. The presence of the xa5 resistant reaction in two ecotypes and in
      accessions with different haplotypes in the candidate region may indicate
      multiple origins or genetic heterogeneity for resistance. In addition, genetic
      differentiation between ecotypes emphasizes the need for controlling for
      population structure in the design of linkage disequilibrium studies in rice.

PMID- 14573487
TI  - A nuclear restorer-of-fertility mutation disrupts accumulation of mitochondrial
      ATP synthase subunit alpha in developing pollen of S male-sterile maize.
AB  - Mitochondrial biogenesis and function depend upon the interaction of
      mitochondrial and nuclear genomes. Forward genetic analysis of mitochondrial
      function presents a challenge in organisms that are obligated to respire. In the
      S-cytoplasmic male sterility (CMS-S) system of maize, expression of mitochondrial
      open reading frames (orf355-orf77) conditions collapse of developing haploid
      pollen. Nuclear restorer-of-fertility mutations that circumvent pollen collapse
      are often homozygous lethal. These spontaneous mutations potentially result from
      disruption of nuclear genes required for mitochondrial gene expression, in
      contrast to homozygous-viable restorer-of-fertility alleles that function to
      block or compensate for the expression of mitochondrial CMS genes. Consistent
      with this hypothesis, the homozygous-lethal restoring allele historically
      designated RfIII was shown to be recessive in diploid pollen produced by
      tetraploid CMS-S plants. Accordingly, the symbol for this allele has been changed
      to restorer-of-fertility lethal 1 (rfl1). In haploid rfl1 pollen, orf355-orf77
      transcripts and mitochondrial transcripts encoding the alpha-subunit of the ATP
      synthase (ATPA) were decreased in abundance. Haploid rfl1 pollen failed to
      accumulate wild-type levels of ATPA protein, indicating that functional
      requirements for mitochondrial protein accumulation are relaxed in maize pollen.
      The CMS-S system and rfl mutations therefore allow for the selection of nuclear
      mutations disrupting mitochondrial biogenesis in a multicellular eukaryote.

PMID- 14573488
TI  - Mu killer causes the heritable inactivation of the Mutator family of transposable
      elements in Zea mays.
AB  - Mutations in a number of genes responsible for the maintenance of transposon
      silencing have been reported. However, the initiation of epigenetic silencing of
      transposable elements is poorly characterized. Here, we report the identification
      of a single dominant locus, Mu killer (Muk), that acts to silence MuDR, the
      autonomous regulatory transposon of the Mutator family of transposable elements
      in maize. Muk results in the methylation of MuDR TIRs and is competent to silence
      one or several active MuDR elements. Silencing by Muk is not dependent on the
      position of the MuDR element and occurs gradually during plant development.
      Transcript levels of the MuDR transposase, mudrA, decrease substantially when Muk
      is present. The other transcript encoded by MuDR, mudrB, also fails to accumulate
      in the poly(A) RNA fraction when MuDR and Muk are combined. Additionally, plants
      undergoing MuDR silencing produce small, mudrA-homologous approximately 26-nt
      RNAs, suggesting a role for RNA-directed DNA methylation in MuDR silencing. MuDR
      elements silenced by Muk remain silenced even in plants that do not inherit Muk,
      suggesting that Muk is required for the initiation of MuDR silencing but not for
      its maintenance.

PMID- 14573489
TI  - An Ac-like transposable element family with transcriptionally active Y-linked
      copies in the white campion, Silene latifolia.
AB  - An RFLP genomic subtraction was used to isolate male-specific sequences in the
      species Silene latifolia. One isolated fragment, SLP2, shares similarity to a
      portion of the Activator (Ac) transposase from Zea mays and to related proteins
      from other plant species. Southern blot analysis of male and female S. latifolia
      genomic DNA shows that SLP2 belongs to a low-copy-number repeat family with two Y
      linked copies. Screening of a S. latifolia male genomic library using SLP2 as a
      probe led to the isolation of five clones, which were partially sequenced. One
      clone contains two large open reading frames that can be joined into a sequence
      encoding a putative protein of 682 amino acids by removing a short intron.
      Database searches and phylogenetic analysis show that this protein belongs to the
      hAT superfamily of transposases, closest to Tag2 (Arabidopsis thaliana), and
      contains all of the defined domains critical for the activity of these
      transposases. PCR with genomic and cDNA templates from S. latifolia male, female,
      and hermaphrodite individuals revealed that one of the Y-linked copies is
      transcriptionally active and alternatively spliced. This is the first report of a
      transcriptionally active transposable element (TE) family in S. latifolia and the
      first DNA transposon residing on a plant Y chromosome. The potential activity and
      regulation of this TE family and its use for Y chromosome gene discovery is
      discussed.

PMID- 14573490
TI  - Distribution of retroelements in centromeres and neocentromeres of maize.
AB  - Fluorescent in situ hybridization was used to examine the distribution of six
      abundant long terminal repeat (LTR) retroelements, Opie, Huck, Cinful-1, Prem
      2/Ji, Grande, and Tekay/Prem-1 on maize pachytene chromosomes. Retroelement
      staining in euchromatin was remarkably uniform, even when we included the
      structurally polymorphic abnormal chromosome 10 (Ab10) in our analysis. This
      uniformity made it possible to use euchromatin as a control for quantitative
      staining intensity measurements in other regions of the genome. The data show
      that knobs, known to function as facultative neocentromeres when Ab10 is present,
      tend to exclude retroelements. A notable exception is Cinful-1, which accumulates
      in TR-1 knob arrays. Staining for each of the six retroelements was also
      substantially reduced in centromeric satellite arrays to an average of 30% of the
      staining in euchromatin. This contrasted with two previously described centromere
      specific retrotransposable (CR) elements that were readily detected in
      centromeres. We suggest that retroelements are relatively rare in centromeres
      because they interrupt the long satellite arrays thought to be required for
      efficient centromere function. CR elements may have evolved mutualistic
      relationships with their plant hosts: they are known to interact with the
      kinetochore protein CENH3 and appear to accumulate in clusters, leaving long
      satellite arrays intact.

PMID- 14573491
TI  - Duplication and diversification in the APETALA1/FRUITFULL floral homeotic gene
      lineage: implications for the evolution of floral development.
AB  - Phylogenetic analyses of angiosperm MADS-box genes suggest that this gene family
      has undergone multiple duplication events followed by sequence divergence. To
      determine when such events have taken place and to understand the relationships
      of particular MADS-box gene lineages, we have identified APETALA1/FRUITFULL-like
      MADS-box genes from a variety of angiosperm species. Our phylogenetic analyses
      show two gene clades within the core eudicots, euAP1 (including Arabidopsis
      APETALA1 and Antirrhinum SQUAMOSA) and euFUL (including Arabidopsis FRUITFULL).
      Non-core eudicot species have only sequences similar to euFUL genes (FUL-like).
      The predicted protein products of euFUL and FUL-like genes share a conserved C
      terminal motif. In contrast, predicted products of members of the euAP1 gene
      clade contain a different C terminus that includes an acidic transcription
      activation domain and a farnesylation signal. Sequence analyses indicate that the
      euAP1 amino acid motifs may have arisen via a translational frameshift from the
      euFUL/FUL-like motif. The euAP1 gene clade includes key regulators of floral
      development that have been implicated in the specification of perianth identity.
      However, the presence of euAP1 genes only in core eudicots suggests that there
      may have been changes in mechanisms of floral development that are correlated
      with the fixation of floral structure seen in this clade.

PMID- 14573492
TI  - Duplication-dependent CG suppression of the seed storage protein genes of maize.
AB  - This study investigates the prevalence of CG and CNG suppression in single- vs.
      multicopy DNA regions of the maize genome. The analysis includes the single- and
      multicopy seed storage proteins (zeins), the miniature inverted-repeat
      transposable elements (MITEs), and long terminal repeat (LTR) retrotransposons.
      Zein genes are clustered on specific chromosomal regions, whereas MITEs and LTRs
      are dispersed in the genome. The multicopy zein genes are CG suppressed and
      exhibit large variations in CG suppression. The variation observed correlates
      with the extent of duplication each zein gene has undergone, indicating that gene
      duplication results in an increased turnover of cytosine residues. Alignment of
      individual zein genes confirms this observation and demonstrates that CG
      depletion results primarily from polarized C:T and G:A transition mutations from
      a less to a more extensively duplicated gene. In addition, transition mutations
      occur primarily in a CG or CNG context suggesting that CG suppression may result
      from deamination of methylated cytosine residues. Duplication-dependent CG
      depletion is likely to occur at other loci as duplicated MITEs and LTR elements,
      or elements inserted into duplicated gene regions, also exhibit CG depletion.

PMID- 14573495
TI  - Fixed contributions designs vs. minimization of global coancestry to control
      inbreeding in small populations.
AB  - Populations with small census sizes are at risk because of the loss of genetic
      variability and the increase of inbreeding and its harmful consequences. For
      situations with different numbers of males and females, several hierarchical
      designs have been proposed to control inbreeding through the fixation of
      individuals' contributions. An alternative method, based on the minimization of
      global coancestry, has been proposed to determine contributions as to yield of
      the lowest levels of inbreeding in the population. We use computer simulations to
      assess the relative efficiency of the different methods. The results show that
      minimizing the global coancestry leads to equal or lower levels of inbreeding in
      the short and medium term, although one of the hierarchical designs provides
      lower asymptotic inbreeding rates and, thus, less net inbreeding in the long
      term. We also investigate the performance of the alternative methods against
      departures from the ideal conditions, such as inbred or differentially related
      base individuals and random failures in the expected contributions. The method of
      minimization of global coancestry turns out to be more flexible and robust under
      these realistic situations.

PMID- 14573494
TI  - Bayesian model choice and search strategies for mapping interacting quantitative
      trait Loci.
AB  - Most complex traits of animals, plants, and humans are influenced by multiple
      genetic and environmental factors. Interactions among multiple genes play
      fundamental roles in the genetic control and evolution of complex traits.
      Statistical modeling of interaction effects in quantitative trait loci (QTL)
      analysis must accommodate a very large number of potential genetic effects, which
      presents a major challenge to determining the genetic model with respect to the
      number of QTL, their positions, and their genetic effects. In this study, we use
      the methodology of Bayesian model and variable selection to develop strategies
      for identifying multiple QTL with complex epistatic patterns in experimental
      designs with two segregating genotypes. Specifically, we develop a reversible
      jump Markov chain Monte Carlo algorithm to determine the number of QTL and to
      select main and epistatic effects. With the proposed method, we can jointly infer
      the genetic model of a complex trait and the associated genetic parameters,
      including the number, positions, and main and epistatic effects of the identified
      QTL. Our method can map a large number of QTL with any combination of main and
      epistatic effects. Utility and flexibility of the method are demonstrated using
      both simulated data and a real data set. Sensitivity of posterior inference to
      prior specifications of the number and genetic effects of QTL is investigated.

PMID- 14573493
TI  - High-resolution crossover maps for each bivalent of Zea mays using recombination
      nodules.
AB  - Recombination nodules (RNs) are closely correlated with crossing over, and,
      because they are observed by electron microscopy of synaptonemal complexes (SCs)
      in extended pachytene chromosomes, RNs provide the highest-resolution cytological
      marker currently available for defining the frequency and distribution of
      crossovers along the length of chromosomes. Using the maize inbred line KYS, we
      prepared an SC karyotype in which each SC was identified by relative length and
      arm ratio and related to the proper linkage group using inversion heterozygotes.
      We mapped 4267 RNs on 2080 identified SCs to produce high-resolution maps of RN
      frequency and distribution on each bivalent. RN frequencies are closely
      correlated with both chiasma frequencies and SC length. The total length of the
      RN recombination map is about twofold shorter than that of most maize linkage
      maps, but there is good correspondence between the relative lengths of the
      different maps when individual bivalents are considered. Each bivalent has a
      unique distribution of crossing over, but all bivalents share a high frequency of
      distal RNs and a severe reduction of RNs at and near kinetochores. The frequency
      of RNs at knobs is either similar to or higher than the average frequency of RNs
      along the SCs. These RN maps represent an independent measure of crossing over
      along maize bivalents.

PMID- 14573496
TI  - Large-scale adaptive hitchhiking upon high recombination in Drosophila simulans.
AB  - Natural selection is expected to leave a characteristic footprint on neighboring
      nucleotide variation through the effects of genetic linkage. The size of the
      region affected is proportional to the strength of selection and greatly reduced
      with the recombinational distance from the selected site. Thus, the genomic
      footprint of selection is generally believed to be restricted to a small DNA
      stretch in normal and highly recombining regions. Here, we study the effect of
      selection on linked polymorphism (hitchhiking effect) by surveying nucleotide
      variation across a highly recombining approximately 88-kb genomic fragment in an
      African population of Drosophila simulans. We find a core region of up to 38 kb
      with a major haplotype at intermediate frequency. The extended haplotype
      structure that gradually vanishes until disappearing is unusual for a highly
      recombining region. Both the presence in the structured genomic domain of a
      single major haplotype depleted of variability and the detected spatial pattern
      of variation along the approximately 88-kb fragment are incompatible with neutral
      predictions in a panmictic population. A major role of demographic effects could
      also be discarded. The observed pattern of variation clearly provides evidence
      that directional selection has acted recently on this region, sweeping out
      variation around a strongly adaptive mutation. Our findings suggest a major role
      of positive selection in shaping DNA variability even in highly recombining
      regions.

PMID- 14573497
TI  - A general statistical framework for mapping quantitative trait loci in nonmodel
      systems: issue for characterizing linkage phases.
AB  - Because of uncertainty about linkage phases of founders, linkage mapping in
      nonmodel, outcrossing systems using molecular markers presents one of the major
      statistical challenges in genetic research. In this article, we devise a
      statistical method for mapping QTL affecting a complex trait by incorporating all
      possible QTL-marker linkage phases within a mapping framework. The advantage of
      this model is the simultaneous estimation of linkage phases and QTL location and
      effect parameters. These estimates are obtained through maximum-likelihood
      methods implemented with the EM algorithm. Extensive simulation studies are
      performed to investigate the statistical properties of our model. In a case study
      from a forest tree, this model has successfully identified a significant QTL
      affecting wood density. Also, the probability of the linkage phase between this
      QTL and its flanking markers is estimated. The implications of our model and its
      extension to more general circumstances are discussed.

PMID- 14573498
TI  - Analysis and exploration of the use of rule-based algorithms and consensus
      methods for the inferral of haplotypes.
AB  - The difficulty of experimental determination of haplotypes from phase-unknown
      genotypes has stimulated the development of nonexperimental inferral methods. One
      well-known approach for a group of unrelated individuals involves using the
      trivially deducible haplotypes (those found in individuals with zero or one
      heterozygous sites) and a set of rules to infer the haplotypes underlying
      ambiguous genotypes (those with two or more heterozygous sites). Neither the
      manner in which this "rule-based" approach should be implemented nor the accuracy
      of this approach has been adequately assessed. We implemented eight variations of
      this approach that differed in how a reference list of haplotypes was derived and
      in the rules for the analysis of ambiguous genotypes. We assessed the accuracy of
      these variations by comparing predicted and experimentally determined haplotypes
      involving nine polymorphic sites in the human apolipoprotein E (APOE) locus. The
      eight variations resulted in substantial differences in the average number of
      correctly inferred haplotype pairs. More than one set of inferred haplotype pairs
      was found for each of the variations we analyzed, implying that the rule-based
      approach is not sufficient by itself for haplotype inferral, despite its
      appealing simplicity. Accordingly, we explored consensus methods in which
      multiple inferrals for a given ambiguous genotype are combined to generate a
      single inferral; we show that the set of these "consensus" inferrals for all
      ambiguous genotypes is more accurate than the typical single set of inferrals
      chosen at random. We also use a consensus prediction to divide ambiguous
      genotypes into those whose algorithmic inferral is certain or almost certain and
      those whose less certain inferral makes molecular inferral preferable.

PMID- 14573499
TI  - A function for subtelomeric DNA in Saccharomyces cerevisiae.
AB  - The subtelomeric DNA sequences from chromosome I of Saccharomyces cerevisiae are
      shown to be inherently poor substrates for meiotic recombination. On the basis of
      these results and prior observations that crossovers near telomeres do not
      promote efficient meiosis I segregation, we suggest that subtelomeric sequences
      evolved to prevent recombination from occurring where it cannot promote efficient
      segregation.

PMID- 14573500
TI  - The sex chromosomes of Silene latifolia revisited and revised.
AB  - Classical studies have established that, during meiosis, the X and Y chromosomes
      of the model dioecious plant Silene latifolia pair over a region at the ends of
      their q arms. We used fluorescence in situ hybridization of two molecular markers
      to demonstrate that this widely accepted model is incorrect. From these data we
      conclude that the homologous arm of the X chromosome is the p arm and that of the
      Y chromosome is the q arm. The establishment of the proper orientation of the
      pseudoautosomal region is essential for mapping and evolutionary studies.

PMID- 14573511
TI  - Accelerated dendritic development of rat cortical pyramidal cells and
      interneurons after biolistic transfection with BDNF and NT4/5.
AB  - Neurotrophins are candidate molecules for regulating dendritogenesis. We report
      here on dendritic growth of rat visual cortex pyramidal and interneurons
      overexpressing 'brain-derived neurotrophic factor' BDNF and 'neurotrophin 4/5'
      NT4/5. Neurons in organotypic cultures were transfected with plasmids encoding
      either 'enhanced green fluorescent protein' EGFP, BDNF/EGFP or NT4/5/EGFP either
      at the day of birth with analysis at 5 days in vitro, or at 5 days in vitro with
      analysis at 10 days in vitro. In pyramidal neurons, both TrkB ligands increased
      dendritic length and number of segments without affecting maximum branch order
      and number of primary dendrites. In the early time window, only infragranular
      neurons were responsive. Neurons in layers II/III became responsive to NT4/5, but
      not BDNF, during the later time window. BDNF and NT4/5 transfectants at 10 days
      in vitro had still significantly shorter dendrites than adult pyramidal neurons,
      suggesting a massive growth spurt after 10 days in vitro. However, segment
      numbers were already in the range of adult neurons. Although this suggested a
      role for BDNF, long-term activity-deprived, and thus BDNF-deprived, pyramidal
      cells developed a dendritic complexity not different from neurons in active
      cultures except for higher spine densities on neurons of layers II/III and VI.
      Neutralization of endogenous NT4/5 causes shorter and less branched dendrites at
      10 days in vitro suggesting an essential role for NT4/5. Neutralization of BDNF
      had no effect. Transfected multipolar interneurons became identifiable during the
      second time window. Both TrkB ligands significantly increased number of segments
      and branch order towards the adult state with little effects on dendritic length.
      The results suggested that early in development BDNF and NT4/5 probably
      accelerate dendritogenesis in an autocrine fashion. In particular, branch
      formation was advanced towards the adult pattern in pyramidal cells and
      interneurons.

PMID- 14573512
TI  - Maternal mRNAs of PEM and macho 1, the ascidian muscle determinant, associate and
      move with a rough endoplasmic reticulum network in the egg cortex.
AB  - Localization of maternal mRNAs in the egg cortex is an essential feature of
      polarity in embryos of Drosophila, Xenopus and ascidians. In ascidians, maternal
      mRNAs such as macho 1, a determinant of primary muscle-cell fate, belong to a
      class of postplasmic RNAs that are located along the animal-vegetal gradient in
      the egg cortex. Between fertilization and cleavage, these postplasmic RNAs
      relocate in two main phases. They further concentrate and segregate in small
      posterior blastomeres into a cortical structure, the centrosome-attracting body
      (CAB), which is responsible for unequal cleavages. By using high-resolution,
      fluorescent, in situ hybridization in eggs, zygotes and embryos of Halocynthia
      roretzi, we showed that macho 1 and HrPEM are localized on a reticulated
      structure situated within 2 mum of the surface of the unfertilized egg, and
      within 8 mum of the surface the vegetal region and then posterior region of the
      zygote. By isolating cortices from eggs and zygotes we demonstrated that this
      reticulated structure is a network of cortical rough endoplasmic reticulum (cER)
      that is tethered to the plasma membrane. The postplasmic RNAs macho 1 and HrPEM
      were located on the cER network and could be detached from it. We also show that
      macho 1 and HrPEM accumulated in the CAB and the cER network. We propose that
      these postplasmic RNAs relocalized after fertilization by following the
      microfilament- and microtubule-driven translocations of the cER network to the
      poles of the zygote. We also suggest that the RNAs segregate and concentrate in
      posterior blastomeres through compaction of the cER to form the CAB. A multimedia
      BioClip 'Polarity inside the egg cortex' tells the story and can be downloaded at
      www.bioclips.com/bioclip.html

PMID- 14573513
TI  - Dystrophin is required for the formation of stable muscle attachments in the
      zebrafish embryo.
AB  - A class of recessive lethal zebrafish mutations has been identified in which
      normal skeletal muscle differentiation is followed by a tissue-specific
      degeneration that is reminiscent of the human muscular dystrophies. Here, we show
      that one of these mutations, sapje, disrupts the zebrafish orthologue of the X
      linked human Duchenne muscular dystrophy (DMD) gene. Mutations in this locus
      cause Duchenne or Becker muscular dystrophies in human patients and are thought
      to result in a dystrophic pathology through disconnecting the cytoskeleton from
      the extracellular matrix in skeletal muscle by reducing the level of dystrophin
      protein at the sarcolemma. This is thought to allow tearing of this membrane,
      which in turn leads to cell death. Surprisingly, we have found that the
      progressive muscle degeneration phenotype of sapje mutant zebrafish embryos is
      caused by the failure of embryonic muscle end attachments. Although a role for
      dystrophin in maintaining vertebrate myotendinous junctions (MTJs) has been
      postulated previously and MTJ structural abnormalities have been identified in
      the Dystrophin-deficient mdx mouse model, in vivo evidence of pathology based on
      muscle attachment failure has thus far been lacking. This zebrafish mutation may
      therefore provide a model for a novel pathological mechanism of Duchenne muscular
      dystrophy and other muscle diseases.

PMID- 14573514
TI  - Tbx5 specifies the left/right ventricles and ventricular septum position during
      cardiogenesis.
AB  - Extensive misexpression studies were carried out to explore the roles played by
      Tbx5, the expression of which is excluded from the right ventricle (RV) during
      cardiogenesis. When Tbx5 was misexpressed ubiquitously, ventricular septum was
      not formed, resulting in a single ventricle. In such heart, left ventricle (LV)
      specific ANF gene was induced. In search of the putative RV factor(s), we have
      found that chick Tbx20 is expressed in the RV, showing a complementary fashion to
      Tbx5. In the Tbx5-misexpressed heart, this gene was repressed. When misexpression
      was spatially partial, leaving small Tbx5-negative area in the right ventricle,
      ventricular septum was shifted rightwards, resulting in a small RV with an
      enlarged LV. Focal expression induced an ectopic boundary of Tbx5-positive and 
      negative regions in the right ventricle, at which an additional septum was
      formed. Similar results were obtained from the transient transgenic mice. In such
      hearts, expression patterns of dHAND and eHAND were changed with definitive
      cardiac abnormalities. Furthermore, we report that human ANF promoter is
      synergistically activated by Tbx5, Nkx2.5 and GATA4. This activation was
      abrogated by Tbx20, implicating the pivotal roles of interactions among these
      heart-specific factors. Taken together, our data indicate that Tbx5 specifies the
      identity of LV through tight interactions among several heart-specific factors,
      and highlight the essential roles of Tbx5 in cardiac development.

PMID- 14573515
TI  - Bar homeodomain proteins are anti-proneural in the Drosophila eye:
      transcriptional repression of atonal by Bar prevents ectopic retinal
      neurogenesis.
AB  - Atonal (Ato)/Math (Mammalian atonal homolog) family proneural proteins are key
      regulators of neurogenesis in both vertebrates and invertebrates. In the
      Drosophila eye, Ato is essential for the generation of photoreceptor neurons. Ato
      expression is initiated at the anterior ridge of the morphogenetic furrow but is
      repressed in the retinal precursor cells behind the furrow to prevent ectopic
      neurogenesis. We show that Ato repression is mediated by the conserved homeobox
      proteins BarH1 and BarH2. Loss of Bar causes cell-autonomous ectopic Ato
      expression, resulting in excess photoreceptor clusters. The initial ommatidial
      spacing at the furrow occurs normally in the absence of Bar, suggesting that the
      ectopic neurogenesis within Bar mutant clones is not due to the lack of Notch (N)
      dependent lateral inhibition. Targeted misexpression of Bar is sufficient to
      repress ato expression. Furthermore, we provide evidence that Bar represses ato
      expression at the level of transcription without affecting the expression of an
      ato activator, Cubitus interruptus (Ci). Thus, we propose that Bar is essential
      for transcriptional repression of ato and the prevention of ectopic neurogenesis
      behind the furrow.

PMID- 14573516
TI  - The potential to induce glial differentiation is conserved between Drosophila and
      mammalian glial cells missing genes.
AB  - Drosophila glial cells missing (gcm) is a key gene that determines the fate of
      stem cells within the nervous system. Two mouse gcm homologs have been
      identified, but their function in the nervous system remains to be elucidated. To
      investigate their function, we constructed retroviral vectors harboring
      Drosophila gcm and two mouse Gcm genes. Expression of these genes appeared to
      influence fibroblast features. In particular, mouse Gcm1 induced the expression
      of astrocyte-specific Ca(2+)-binding protein, S100beta, in those cells.
      Introduction of the mouse Gcm1 gene in cultured cells from embryonic brains
      resulted in the induction of an astrocyte lineage. This effect was also observed
      by in utero injection of retrovirus harboring mouse Gcm1 into the embryonic
      brain. However, cultures from mouse Gcm1-deficient mouse brains did not exhibit
      significant reductions in the number of astrocytes. Furthermore, in situ
      hybridization analysis of mouse Gcm1 mRNA revealed distinct patterns of
      expression in comparison with other well-known glial markers. The mammalian
      homolog of Drosophila gcm, mouse Gcm1, exhibits the potential to induce
      gliogenesis, but may function in the generation of a minor subpopulation of glial
      cells.

PMID- 14573517
TI  - The DUET gene is necessary for chromosome organization and progression during
      male meiosis in Arabidopsis and encodes a PHD finger protein.
AB  - Progression through the meiotic cell cycle is an essential part of the
      developmental program of sporogenesis in plants. The duet mutant of Arabidopsis
      was identified as a male sterile mutant that lacked pollen and underwent an
      aberrant male meiosis. Male meiocyte division resulted in the formation of two
      cells instead of a normal tetrad. In wild type, male meiosis extends across two
      successive bud positions in an inflorescence whereas in duet, meiotic stages
      covered three to five bud positions indicating defective progression. Normal
      microspores were absent in the mutant and the products of the aberrant meiosis
      were uni- to tri-nucleate cells that later degenerated, resulting in anthers
      containing largely empty locules. Defects in male meiotic chromosome organization
      were observed starting from diplotene and extending to subsequent stages of
      meiosis. There was an accumulation of meiotic structures at metaphase 1,
      suggesting an arrest in cell cycle progression. Double mutant analysis revealed
      interaction with dyad, a mutation causing chromosome cohesion during female
      meiosis. Cloning and molecular analysis of DUET indicated that it potentially
      encodes a PHD-finger protein and shows specific expression in male meiocytes.
      Taken together these data suggest that DUET is required for male meiotic
      chromosome organization and progression.

PMID- 14573518
TI  - Embryonic atrial function is essential for mouse embryogenesis, cardiac
      morphogenesis and angiogenesis.
AB  - The requirement for atrial function in developing heart is unknown. To address
      this question, we have generated mice deficient in atrial myosin light chain 2
      (MLC2a), a major structural component of the atrial myofibrillar apparatus.
      Inactivation of the Mlc2a gene resulted in severely diminished atrial contraction
      and consequent embryonic lethality at ED10.5-11.5, demonstrating that atrial
      function is essential for embryogenesis. Our data also address two longstanding
      questions in cardiovascular development: the connection between function and form
      during cardiac morphogenesis, and the requirement for cardiac function during
      vascular development. Diminished atrial function in MLC2a-null embryos resulted
      in a number of consistent secondary abnormalities in both cardiac morphogenesis
      and angiogenesis. Our results unequivocally demonstrate that normal cardiac
      function is directly linked to normal morphogenic development of heart and
      vasculature. These data have important implications for the etiology of
      congenital heart disease.

PMID- 14573519
TI  - Bowl is required downstream of Notch for elaboration of distal limb patterning.
AB  - In the Drosophila leg, activation of Notch leads to the establishment of the
      joints that subdivide the appendage into segments. We find that mutations in bowl
      result in similar phenotypes to Notch, causing fusion and truncations of tarsal
      segments (tarsomeres) and, like its close relative Odd-skipped, Bowl is produced
      in response to Notch signalling at a subset of segment boundaries. However,
      despite the fact that bowl mutant clones result in fusion of tarsomeres, Bowl
      protein is only found at the t1/tibial and t5/pretarsal boundaries, not at
      tarsomere joints. One hypothesis to reconcile these data is that bowl has a role
      at an earlier stage in tarsal development. We therefore investigated the effects
      of bowl mutations on the expression of leg 'gap' genes that confer regional
      identity on the developing leg. Several of these genes have altered expression in
      bowl mutant cells. For example, bric-a-brac2 is normally expressed in the central
      part of the tarsus domain but expands into distal and proximal regions in bowl
      clones. Conversely, ectopic bowl leads to a reduction in bric-a-brac2, with a
      concomitant expansion of proximal (t1) and distal (t5) tarsomere fates. The bowl
      gene is therefore required for the elaboration of pattern in the tarsus and its
      effects suggest a progressive model for the determination of P/D identities. This
      mechanism might be important in the diversification of arthropod limbs, because
      it explains how segmented tarsomeres could have arisen from an ancestral limb
      with an unsegmented tarsus.

PMID- 14573520
TI  - Role of melanoma chondroitin sulphate proteoglycan in patterning stem cells in
      human interfollicular epidermis.
AB  - Human interfollicular epidermis is renewed by stem cells that are clustered in
      the basal layer in a patterned, non-random distribution. Stem cells can be
      distinguished from other keratinocytes by high expression of beta1 integrins and
      lack of expression of terminal differentiation markers; they divide infrequently
      in vivo but form actively growing colonies in culture. In a search for additional
      stem cell markers, we observed heterogeneous epidermal expression of melanoma
      chondroitin sulphate proteoglycan (MCSP). MCSP was expressed by those
      keratinocytes with the highest beta1 integrin levels. In interfollicular
      epidermis, expression was confined to non-cycling cells and, in culture, to self
      renewing clones. However, fluorescence-activated cell sorting on the basis of
      MCSP and beta1 integrin expression gave no more enrichment for clonogenic
      keratinocytes than sorting for beta1 integrins alone. To interfere with
      endogenous MCSP, we retrovirally infected keratinocytes with a chimera of the CD8
      extracellular domain and the MCSP cytoplasmic domain. CD8/MCSP did not affect
      keratinocyte proliferation or differentiation but the cohesiveness of
      keratinocytes in isolated clones or reconstituted epidermal sheets was greatly
      reduced. CD8/MCSP caused stem cell progeny to scatter without differentiating.
      CD8/MCSP did not alter keratinocyte motility but disturbed cadherin-mediated cell
      cell adhesion and the cortical actin cytoskeleton, effects that could be mimicked
      by inhibiting Rho. We conclude that MCSP is a novel marker for epidermal stem
      cells that contributes to their patterned distribution by promoting stem cell
      clustering.

PMID- 14573521
TI  - Mutation of weak atrium/atrial myosin heavy chain disrupts atrial function and
      influences ventricular morphogenesis in zebrafish.
AB  - The embryonic vertebrate heart is composed of two major chambers, a ventricle and
      an atrium, each of which has a characteristic size, shape and functional capacity
      that contributes to efficient circulation. Chamber-specific gene expression
      programs are likely to regulate key aspects of chamber formation. Here, we
      demonstrate that epigenetic factors also have a significant influence on chamber
      morphogenesis. Specifically, we show that an atrium-specific contractility defect
      has a profound impact on ventricular development. We find that the zebrafish
      locus weak atrium encodes an atrium-specific myosin heavy chain that is required
      for atrial myofibrillar organization and contraction. Despite their atrial
      defects, weak atrium mutants can maintain circulation through ventricular
      contraction. However, the weak atrium mutant ventricle becomes unusually compact,
      exhibiting a thickened myocardial wall, a narrow lumen and changes in myocardial
      gene expression. As weak atrium/atrial myosin heavy chain is expressed only in
      the atrium, the ventricular phenotypes in weak atrium mutants represent a
      secondary response to atrial dysfunction. Thus, not only is cardiac form
      essential for cardiac function, but there also exists a reciprocal relationship
      in which function can influence form. These findings are relevant to our
      understanding of congenital defects in cardiac chamber morphogenesis.

PMID- 14573523
TI  - Dissection of floral induction pathways using global expression analysis.
AB  - Flowering of the reference plant Arabidopsis thaliana is controlled by several
      signaling pathways, which converge on a small set of genes that function as
      pathway integrators. We have analyzed the genomic response to one type of floral
      inductive signal, photoperiod, to dissect the function of several genes
      transducing this stimulus, including CONSTANS, thought to be the major output of
      the photoperiod pathway. Comparing the effects of CONSTANS with those of
      FLOWERING LOCUS T, which integrates inputs from CONSTANS and other floral
      inductive pathways, we find that expression profiles of shoot apices from plants
      with mutations in either gene are very similar. In contrast, a mutation in LEAFY,
      which also acts downstream of CONSTANS, has much more limited effects. Another
      pathway integrator, SUPPRESSOR OF OVEREXPRESSION OF CO 1, is responsive to acute
      induction by photoperiod even in the presence of the floral repressor encoded by
      FLOWERING LOCUS C. We have discovered a large group of potential floral
      repressors that are down-regulated upon photoperiodic induction. These include
      two AP2 domain-encoding genes that can repress flowering. The two paralogous
      genes, SCHLAFMUTZE and SCHNARCHZAPFEN, share a signature with partial
      complementarity to the miR172 microRNA, whose precursor we show to be induced
      upon flowering. These and related findings on SPL genes suggest that microRNAs
      play an important role in the regulation of flowering.

PMID- 14573522
TI  - Ebf gene function is required for coupling neuronal differentiation and cell
      cycle exit.
AB  - Helix-loop-helix transcription factors of the Ebf/Olf1 family have previously
      been implicated in the control of neurogenesis in the central nervous system in
      both Xenopus laevis and the mouse, but their precise roles have remained unclear.
      We have characterised two family members in the chick, and have performed a
      functional analysis by gain- and loss-of-function experiments. This study
      revealed several specific roles for Ebf genes in the spinal cord and hindbrain
      regions of higher vertebrates, and enabled their precise positioning along the
      neurogenic cascade. During neurogenesis, cell cycle exit appears to be tightly
      coupled to migration to the mantle layer and to neuronal differentiation. We show
      that antagonizing Ebf gene activity allows the uncoupling of these processes. Ebf
      gene function is necessary to initiate neuronal differentiation and migration
      toward the mantle layer in neuroepithelial progenitors, but it is not required
      for cell cycle exit. Ebf genes therefore appear to be master controllers of
      neuronal differentiation and migration, coupling them to cell cycle exit and
      earlier steps of neurogenesis. Mutual activation between proneural and Ebf genes
      suggests that besides their involvement in the engagement of differentiation, Ebf
      genes may also participate in the stabilisation of the committed state. Finally,
      gain-of-function data raise the possibility that, in addition to these general
      roles, Ebf genes may be involved in neuronal subtype specification in particular
      regions of the CNS.

PMID- 14573524
TI  - Genome size variations in diploid African Coffea species.
AB  - Flow cytometry was conducted to evaluate genome size diversity among African
      diploid species of the Coffea genus. The study included 15 species and six new
      taxa from Congolese and Cameroonian forest regions which have yet to be
      botanically characterized. Between-population differences were also recorded in
      some cases. These evaluations using an internal standard were highly correlated
      with previous results obtained with an external standard, but differences of up
      to 18 % existed for some species, involving stoichiometric errors. Consequently,
      genome size variation between species and within species are discussed as true
      genome size differences or stoichiometric errors. Environmental and phenotypic
      correlations with genome size are also discussed.

PMID- 14573525
TI  - Aechmea pectinata: a hummingbird-dependent bromeliad with inconspicuous flowers
      from the rainforest in south-eastern Brazil.
AB  - The pollination biology of Aechmea pectinata (Bromeliaceae) was studied in a
      submontane rainforest in south-eastern Brazil. This species has a mainly clumped
      distribution and its aggregated individuals are likely to be clones. From October
      to January, during the flowering period, the distal third of its leaves becomes
      red. The inflorescence produces 1-15 flowers per day over a period of 20-25 d.
      The flowers are inconspicuous, greenish-white coloured, tubular shaped with a
      narrow opening, and the stigma is situated just above the anthers. Anthesis
      begins at 0400 h and flowers last for about 13 h. The highest nectar volume and
      sugar concentration occur between 0600 and 1000 h, and decrease throughout the
      day. Aechmea pectinata is self-incompatible and therefore pollinator-dependent.
      Hummingbirds are its main pollinators (about 90 % of the visits), visiting
      flowers mainly in the morning. There is a positive correlation between the number
      of hummingbird visits per inflorescence and the production of nectar, suggesting
      that the availability of this resource is important in attracting and maintaining
      visitors. The arrangement of the floral structures favours pollen deposition on
      the bill of the hummingbirds. Flowers in clumps promote hummingbird
      territoriality, and a consequence is self-pollination in a broader sense
      (geitonogamy) as individuals in assemblages are genetically close. However, trap
      lining and intruding hummingbirds promote cross-pollination. These observations
      suggest that successful fruit set of A. pectinata depends on both the spatial
      distribution of its individuals and the interactions among hummingbirds.

PMID- 14573526
TI  - Expression profiling of lymphocyte plasma membrane proteins.
AB  - The physicochemical properties of plasma membrane proteins of mammalian cells
      render them refractory to systematic analysis by two-dimensional electrophoresis.
      We have therefore used in vivo cell surface labeling with a water-soluble
      biotinylation reagent, followed by cell lysis and membrane purification, prior to
      affinity capture of biotinylated proteins. Purified membrane proteins were then
      separated by solution-phase isoelectric focusing and SDS-PAGE and identified by
      high-pressure liquid chromatography electrospray/tandem mass spectrometry. Using
      this approach, we identified 42 plasma membrane proteins from a murine T cell
      hybridoma and 46 from unfractionated primary murine splenocytes. These included
      three unexpected proteins; nicastrin, osteoclast inhibitory lectin, and a
      transmembrane domain-containing hypothetical protein of 11.4 kDa. Following
      stimulation of murine splenocytes with phorbol ester and calcium ionophore, we
      observed differences in expression of CD69, major histocompatibility complex
      class II molecules, the glucocorticoid-induced TNF receptor family-related gene
      product, and surface immunoglobulin M and D that were subsequently confirmed by
      Western blot or flow cytometric analysis. This approach offers a generic and
      powerful strategy for investigating differential expression of surface proteins
      in many cell types under varying environmental and pathophysiological conditions.

PMID- 14573527
TI  - The role of microtubule-associated protein 2c in the reorganization of
      microtubules and lamellipodia during neurite initiation.
AB  - During neurite initiation, cells surrounded by a flattened, actin-rich
      lamellipodium transform to produce thin, microtubule-filled neurite shafts tipped
      by actin-rich growth cones, but little is known about this transformation. Our
      detailed time-lapse analyses of cultured hippocampal neurons, a widely used model
      system for neuronal development, revealed that neurites emerge from segmented
      lamellipodia, which then gradually extend from the cell body to become nascent
      growth cones. This suggests that actin- and microtubule-rich structures are
      reorganized in a coordinated manner. We hypothesized that proteins such as
      microtubule-associated protein 2 (MAP2), which can interact with both
      cytoskeletal components, might be critically involved in neurite initiation. Live
      cell video and fluorescence microscopy in Neuro-2a cells showed that expression
      of MAP2c triggers neurite formation via rapid accumulation and bundling of
      stable, MAP2c-bound microtubules, concurrent with a gradual transformation of
      lamellipodia into nascent growth cones. The microtubule-stabilizing agent Taxol
      did not mimic this effect, suggesting that the ability of MAP2c to stabilize
      microtubules is not sufficient for neurite initiation. However, combination of
      Taxol treatment with actin disruption induced robust process formation,
      suggesting that inhibitory effects of F-actin need to be overcome as well.
      Neurite initiation by MAP2c required its microtubule-binding domain and was
      enhanced by its binding domain for cAMP-dependent protein kinase (PKA). MAP2c
      mutants defective in both PKA and microtubule binding acted as dominant negative
      inhibitors of neurite initiation in neuroblastoma cells and primary hippocampal
      neurons. Together, these data suggest that MAP2c bears functions that both
      stabilize microtubules and directly or indirectly alter actin organization during
      neurite initiation.

PMID- 14573528
TI  - Lack of evidence for sprouting of Abeta afferents into the superficial laminas of
      the spinal cord dorsal horn after nerve section.
AB  - The central arborizations of large myelinated cutaneous afferents normally extend
      as far dorsally as the ventral part of lamina II in rat spinal cord. Woolf et al.
      (1992) reported that after nerve injury some of these afferents sprouted into
      lamina I and the dorsal part of lamina II, and it has been suggested that this
      could contribute to allodynia associated with neuropathic pain. Part of the
      evidence for sprouting was on the basis of the use of cholera toxin B subunit as
      a selective tracer for A-fibers, and the validity of this approach has recently
      been questioned; however, sprouting was also reported in experiments involving
      intra-axonal labeling of chronically axotomized afferents. We have used intra
      axonal labeling in the rat to examine central terminals of 58 intact sciatic
      afferents of presumed cutaneous origin and 38 such afferents axotomized 7-10
      weeks previously. Both normal and axotomized populations included axons with hair
      follicle afferent-like morphology and arbors that entered the ventral half of
      lamina II; however, none of these extended farther dorsally. We also performed
      bulk labeling of myelinated afferents by injecting biotinylated dextran into the
      lumbar dorsal columns bilaterally 8-11 weeks after unilateral sciatic nerve
      section. We observed that both ipsilateral and contralateral to the sectioned
      nerve, arbors of axons with hair follicle afferent-like morphology in the sciatic
      territory extended only as far as the ventral half of lamina II. Therefore these
      results do not support the hypothesis that Abeta afferents sprout into the
      superficial laminas after nerve section.

PMID- 14573529
TI  - Involvement of AMPA receptor GluR2 subunits in stimulus-reward learning: evidence
      from glutamate receptor gria2 knock-out mice.
AB  - Presence of the glutamate receptor 2 (GluR2) subunit prevents calcium influx
      through AMPA-receptor complexes; deletion of this subunit results in enhanced
      hippocampal long-term potentiation. We investigated whether mice lacking the
      GluR2 subunit [gria2 knock-out (KO) mice] displayed impairments in learning
      stimulus-reward associations, and the subsequent ability of reward-paired cues to
      control motivated behavior. Both gria2 KO and wild-type (WT) mice learned to
      associate a light/tone stimulus with food delivery, as evidenced by approach
      toward the food magazine after the presentation of the cues (pavlovian
      conditioning). Subsequently, the cues also served to reinforce an operant
      response in both KO and WT mice (conditioned reinforcement), although response
      rates were greater in gria2 KOs. Responding for conditioned reinforcement was
      enhanced after 0.5 mg/kg amphetamine administration in WT mice, but not in KO
      mice. The ability of the cues to elicit approach behavior (conditioned approach)
      and to enhance responding for the reward (pavlovian-to-instrumental transfer;
      PIT) were also impaired in gria2 KO mice. This pattern of behavior resembles that
      seen after lesions of the central nucleus of the amygdala (CeA), an area rich in
      GluR2-containing AMPA receptors. Immunostaining revealed reduced GluR1 expression
      within both the basolateral amygdala and the CeA, suggesting that the behavioral
      deficits observed were unlikely to be caused by compensatory changes in GluR1.
      These results suggest that GluR2-containing AMPA receptors, possibly within the
      CeA, are critical for the formation of stimulus-reward associations necessary for
      PIT and conditioned approach, but are not involved in the plastic processes
      underlying the attribution of motivational value to the conditioned stimulus
      (CS).

PMID- 14573530
TI  - Synchronization of a nonlinear oscillator: processing the cf component of the
      echo-response signal in the cochlea of the mustached bat.
AB  - Cochlear microphonic potential (CM) was recorded from the CF2 region and the
      sparsely innervated zone (the mustached bat's cochlea fovea) that is specialized
      for analyzing the Doppler-shifted echoes of the first-harmonic (approximately 61
      kHz) of the constant-frequency component of the echolocation call. Temporal
      analysis of the CM, which is tuned sharply to the 61 kHz cochlear resonance,
      revealed that at the resonance frequency, and within 1 msec of tone onset, CM is
      broadly tuned with linear magnitude level functions. CM measured during the
      ongoing tone and in the ringing after tone offset is 50 dB more sensitive, is
      sharply tuned, has compressive level functions, and the phase leads onset CM by
      90 degrees: an indication that cochlear responses are amplified during maximum
      basilar membrane velocity. For high-level tones above the resonance frequency, CM
      appears at tone onset and after tone offset. Measurements indicate that the two
      oscillators responsible for the cochlear resonance, presumably the basilar and
      tectorial membranes, move together in phase during the ongoing tone, thereby
      minimizing net shear between them and hair cell excitation. For tones within 2
      kHz of the cochlear resonance the frequency of CM measured within 2 msec of tone
      onset is not that of the stimulus but is proportional to it. For tones just below
      the cochlear resonance region CM frequency is a constant amount below that of the
      stimulus depending on CM measurement delay from tone onset. The frequency
      responses of the CM recorded from the cochlear fovea can be accounted for through
      synchronization between the nonlinear oscillators responsible for the cochlear
      resonance and the stimulus tone.

PMID- 14573531
TI  - Caspase-dependent and caspase-independent oligodendrocyte death mediated by AMPA
      and kainate receptors.
AB  - Oligodendrocytes are vulnerable to excitotoxic signals mediated by AMPA receptors
      and by high- and low-affinity kainate receptors. Here we investigated the nature
      of the cell death triggered by activation of these receptors in primary cultures
      of oligodendrocytes from the rat optic nerve. Activation of AMPA receptors at
      both submaximal and maximal concentrations of the agonist induced massive calcium
      entry, mitochondrial depolarization, and a rise in the level of reactive oxygen
      species that correlated with a decrease in the levels of reduced glutathione. In
      addition, excitotoxicity initiated by submaximal, but not maximal, activation of
      AMPA receptors was prevented by caspase-3 blockade and by the concomitant
      blockade of caspases 8 and 9. In turn, maximal activation of high- or low
      affinity kainate receptors induced mitochondrial events and toxicity levels
      similar to those observed with submaximal activation of AMPA receptors. In
      contrast to AMPA receptor-mediated insults, calcineurin inhibition or caspase-9
      blockade was sufficient to prevent cell death triggered by both types of kainate
      receptors. Consistent with these results, prolonged glutamate receptor activation
      in freshly isolated optic nerves caused selective activation of caspase-3 and
      chromatin condensation in oligodendrocytes. Overall, the evidence presented here
      indicates that oligodendrocyte death by excitotoxicity is mediated by caspase
      dependent and -independent mechanisms.

PMID- 14573533
TI  - Phonological grammar shapes the auditory cortex: a functional magnetic resonance
      imaging study.
AB  - Languages differ depending on the set of basic sounds they use (the inventory of
      consonants and vowels) and on the way in which these sounds can be combined to
      make up words and phrases (phonological grammar). Previous research has shown
      that our inventory of consonants and vowels affects the way in which our brains
      decode foreign sounds (Goto, 1971; Naatanen et al., 1997; Kuhl, 2000). Here, we
      show that phonological grammar has an equally potent effect. We build on previous
      research, which shows that stimuli that are phonologically ungrammatical are
      assimilated to the closest grammatical form in the language (Dupoux et al.,
      1999). In a cross-linguistic design using French and Japanese participants and a
      fast event-related functional magnetic resonance imaging (fMRI) paradigm, we show
      that phonological grammar involves the left superior temporal and the left
      anterior supramarginal gyri, two regions previously associated with the
      processing of human vocal sounds.

PMID- 14573532
TI  - Rapid signaling of estrogen in hypothalamic neurons involves a novel G-protein
      coupled estrogen receptor that activates protein kinase C.
AB  - Classically, 17beta-estradiol (E2) is thought to control homeostatic functions
      such as reproduction, stress responses, feeding, sleep cycles, temperature
      regulation, and motivated behaviors through transcriptional events. Although it
      is increasingly evident that E2 can also rapidly activate kinase pathways to have
      multiple downstream actions in CNS neurons, the receptor(s) and the signal
      transduction pathways involved have not been identified. We discovered that E2
      can alter mu-opioid and GABA neurotransmission rapidly through nontranscriptional
      events in hypothalamic GABA, proopiomelanocortin (POMC), and dopamine neurons.
      Therefore, we examined the effects of E2 in these neurons using whole-cell
      recording techniques in ovariectomized female guinea pigs. E2 reduced rapidly the
      potency of the GABAB receptor agonist baclofen to activate G-protein-coupled,
      inwardly rectifying K+ channels in hypothalamic neurons. These effects were
      mimicked by the membrane impermeant E2-BSA and selective estrogen receptor
      modulators, including a new diphenylacrylamide compound, STX, that does not bind
      to intracellular estrogen receptors alpha or beta, suggesting that E2 acts
      through a unique membrane receptor. We characterized the coupling of this
      estrogen receptor to a Galpha(q)-mediated activation of phospholipase C, leading
      to the upregulation of protein kinase Cdelta and protein kinase A activity in
      these neurons. Moreover, using single-cell reverse transcription-PCR, we
      identified the critical transcripts, PKCdelta and its downstream target adenylyl
      cyclase VII, for rapid, novel signaling of E2 in GABA, POMC, and dopamine
      neurons. Therefore, this unique Gq-coupled estrogen receptor may be involved in
      rapid signaling in hypothalamic neurons that are critical for normal homeostatic
      functions.

PMID- 14573534
TI  - Cross-repressive interaction of the Olig2 and Nkx2.2 transcription factors in
      developing neural tube associated with formation of a specific physical complex.
AB  - In developing neural tube, the basic helix-loop-helix (bHLH) transcription factor
      Olig2 interacts with the homeodomain transcription factor Nkx2.2 at two distinct
      stages. During neuronogenesis, a cross-repressive interaction appears to
      establish the precise boundary between the p3 and pMN domains. At later times, a
      cooperative interaction is noted because Nkx2.2 promotes maturation of
      oligodendrocyte progenitor cells specified by expression of Olig2. We show here
      that the Olig2 protein can form a physical complex with Nkx2.2 protein in
      mammalian cells and yeast two-hybrid trap assay. This interaction is specific
      because Olig2 does not bind to a biologically irrelevant homeodomain
      transcription factor (Nkx6.1), and Nkx2.2 does not interact with a biologically
      irrelevant bHLH protein (NeuroD). Deletion mapping analysis suggests that
      formation of an Olig2-Nkx2.2 physical complex is insufficient for the induction
      of oligodendrocyte progenitors in developing spine; however, the protein-protein
      interaction observed might be important for the cross-repressive interaction
      between Olig2 and Nkx2.2 that helps to establish the pMN-p3 boundary in the
      developing spinal cord.

PMID- 14573535
TI  - Short-term dynamics of a mixed chemical and electrical synapse in a rhythmic
      network.
AB  - In the rhythmically active pyloric circuit of the spiny lobster, the synapse
      between the lateral pyloric (LP) neuron and pyloric constrictor (PY) neuron has
      an inhibitory depressing chemical and an electrical component. To understand how
      the dynamics of the LP-->PY synapse affect the relative firing times between
      these two neurons in an ongoing rhythm, we characterized the dynamics of the LP-
      >PY synapse after a pharmacological block of ongoing activity. When a train of
      voltage pulses was applied to the voltage-clamped LP neuron, the inhibitory
      chemical component of the postsynaptic potential (PSP) in the PY neuron rapidly
      depressed. Thus, after the first few pulses, the PSP was either hyperpolarizing
      or depolarizing, depending on the interpulse duration, with shorter interpulse
      durations producing depolarizing PSPs. To characterize the synaptic response
      during rhythmic activity, we played back prerecorded realistic waveforms in the
      voltage-clamped LP neuron. After an initial transient, the resulting PSP in PY
      was always depolarizing, suggesting that in an ongoing rhythm, the electrical
      component of the synapse is dominant. However, our results indicate that the
      chemical component of the synapse acts to delay the peak time of the PSP and to
      reduce its amplitude, and that these effects become more important at slower
      cycle periods.

PMID- 14573536
TI  - Thalamocortical angular tuning domains within individual barrels of rat
      somatosensory cortex.
AB  - In the rodent somatosensory cortex, whisker-related barrels in layer IV are
      morphological counterparts of functional cortical columns that extend throughout
      the cortical depth. We used microelectrode recordings and spike-triggered
      averaging of field potentials evoked by single thalamic barreloid neurons to
      investigate functional thalamocortical microcircuits. The function of such
      circuits was probed by deflecting the principal whisker of a barrel in different
      angular directions. We found that individual barrels contain minicolumns of
      neurons preferring the same deflection angle. Angular tuning domains are
      established by convergent inputs from thalamocortical cells with corresponding
      angular preferences. Processing within such domains may depend on local
      connectivity among vertically aligned barrel neurons.

PMID- 14573537
TI  - Ontogeny of the pre-Botzinger complex in perinatal rats.
AB  - The aim of this study was to provide a systematic examination of the ontogenesis
      of the mammalian respiratory rhythm generating center, the pre-Botzinger complex
      (pre-BotC). A combination of immunohistochemical markers and electrophysiological
      recordings was used to determine the time of inception of the pre-BotC and the
      developmental changes during the perinatal period in rats spanning from embryonic
      day 15 (E15) to postnatal day 7. The first clear indication of neurons
      immunopositive for neurokinin-1 receptors (NK1Rs) and somatostatin expression,
      two proposed markers for pre-BotC neurons, was at approximately E17. Birth dating
      of neurons in the ventrolateral medulla using 5-bromo-2'-deoxyuridine
      demonstrated that NK1R-positive neurons populating the area of the pre-BotC
      during late E16-E18 are born at E12.5-E13.5, approximately 2 d later than
      adjacent NK1R-positive neurons in the ventrolateral medulla. Extracellular
      recordings of neuronal populations within the pre-BotC of perinatal medullary
      slice preparations demonstrated that the onset of rhythmical respiratory
      discharge commences at approximately E17. Application of substance P, a ligand
      for NK1R receptors, to the media bathing E17 medullary slice and brainstem-spinal
      cord preparations resulted in a marked increase in respiratory frequency. These
      data provide insights into the ontogeny of the pre-BotC, giving fundamental
      information on the genesis, settlement, and inception of rhythmic activity within
      the group of neurons proposed to be responsible for the respiratory rhythm
      generation. Furthermore, this provides the foundation for further analyses of
      cell lineage, the transcriptional control of respiratory neuronal development,
      and electrophysiological and pharmacological properties of the pre-BotC during
      the prenatal period.

PMID- 14573539
TI  - GLR-1, a non-NMDA glutamate receptor homolog, is critical for long-term memory in
      Caenorhabditis elegans.
AB  - Long-term memory for habituation to tap in Caenorhabditis elegans depends on glr
      1, a homolog of mammalian non-NMDA glutamate receptors; mutations in glr-1
      blocked long-term memory formation. Green fluorescent protein (GFP) constructs
      were used to visualize glr-1 expression in the interneurons of the mechanosensory
      circuit and synaptobrevin in the tap sensory neurons of trained and untrained
      worms. Trained animals had less GLR-1::GFP expression than untrained animals;
      there was no difference in the vesicle marker synaptobrevin. Heat shock during
      training blocked both the behavioral expression of long-term memory and the
      change in GLR-1::GFP expression. Thus, long-term memory in C. elegans is
      dependent on glr-1 and likely involves changes in the expression or localization
      of glutamate receptors.

PMID- 14573538
TI  - Prolonged habituation of the gill-withdrawal reflex in Aplysia depends on protein
      synthesis, protein phosphatase activity, and postsynaptic glutamate receptors.
AB  - Despite representing perhaps the simplest form of memory, habituation is not yet
      well understood mechanistically. We used a reduced preparation to analyze the
      neurobiological mechanisms of persistent habituation of a simple behavior, the
      defensive withdrawal reflex of the marine snail Aplysia californica. This
      preparation permits direct infusion of drugs into the abdominal ganglion during
      training via a cannula in the abdominal artery. Using siphon-elicited gill
      withdrawal, we demonstrate habituation of withdrawal that persists for 1-6 hr
      after repeated, spaced blocks of habituating stimulation. This form of
      habituation exhibits site specificity and requires protein synthesis because it
      is blocked by the presence of anisomycin, a protein synthesis inhibitor. We also
      find that habituation of gill withdrawal requires protein phosphatase activity,
      because it is blocked by okadaic acid, an inhibitor of protein phosphatase.
      Finally, habituation of gill withdrawal requires activation of NMDA-type and AMPA
      type postsynaptic receptors within the abdominal ganglion, because it is blocked
      by infusion of dl-2-amino-5-phosphonovaleric acid or 6,7-dinitroquinoxaline-2,3
      dione. The requirement for activation of postsynaptic glutamatergic receptors
      indicates that homosynaptic depression, an exclusively presynaptic mechanism that
      has been implicated previously in habituation in Aplysia, does not play a
      significant role in persistent habituation of the withdrawal reflex. Our results
      indicate that postsynaptic mechanisms, possibly including modulation of glutamate
      receptor function, play a major, heretofore unsuspected, role in habituation in
      Aplysia.

PMID- 14573540
TI  - Firing properties of spinal interneurons during voluntary movement. I. State
      dependent regularity of firing.
AB  - The firing properties of single spinal interneurons (INs) were studied in five
      awake, behaving monkeys performing isometric or auxotonic flexion-extension
      torques at the wrist. INs tended to fire tonically at rest (mean rate, 14 spikes
      (sp)/sec) and during generation of static torque (mean rate, 19 sp/sec in
      flexion, 24 sp/sec in extension). INs exhibited regular firing, with
      autocorrelation functions showing clear periodic features and a mean coefficient
      of variation of interspike intervals (CV) of 0.55 during production of static
      torque. For the population, there was an inverse correlation between CV and mean
      rate. However, 46% of the INs had task-dependent changes in regularity that were
      not predicted by changes in firing rate, suggesting that their firing pattern is
      determined not only by the intrinsic properties of the neurons but also by the
      properties of its synaptic inputs. INs showed two main response types to passive
      wrist displacement: biphasic and coactivation. Cells with these sensory responses
      had different, stereotypical temporal activity profiles and firing regularity
      during active movement. However, INs having correlational linkages with forearm
      muscles, identified as features in spike-triggered averages of electromyographic
      activity, did not exhibit unique responses or firing properties, although they
      tended to fire more regularly than other INs. This suggests the lack of a precise
      mapping of inputs to outputs for the spinal premotor network.

PMID- 14573541
TI  - Firing properties of spinal interneurons during voluntary movement. II.
      Interactions between spinal neurons.
AB  - The relationship between the activity of pairs of simultaneously recorded spinal
      interneurons (INs) in the cervical enlargement was studied in five monkeys
      performing voluntary wrist movements. The tendency for INs to exhibit similar
      response properties and synchronized firing was tested as a function of physical
      distance between the cells and their correlational linkages with forearm muscles.
      Nearby INs tended to have more similar torque and direction turning (signal
      correlation) and more similar response profiles (e.g., tonic vs phasic firing)
      than INs that were far apart. This suggests that nearby cells receive common
      synaptic input. In contrast, the trial-to-trial covariation of rate around the
      mean rate for all trials (noise correlation) was independent of the distance
      between the neurons. Furthermore, signal and noise correlation were independent,
      suggesting different underlying mechanisms. Surprisingly, spike-to-spike
      correlation between INs was relatively infrequent and weak, as measured by cross
      correlation histograms. In contrast, single motor units (SMUs) in forearm muscles
      fired more synchronously, particularly for SMUs in single extensor muscles.
      Either common drive to INs is too weak to induce synchronized firing, or there is
      an active decorrelation mechanism within IN networks.

PMID- 14573542
TI  - Receptive field plasticity profoundly alters the cutaneous parallel fiber
      synaptic input to cerebellar interneurons in vivo.
AB  - The cutaneous parallel fiber (PF) receptive fields of cerebellar stellate and
      basket cells in the cerebellar C3 zone in vivo are normally very small but can be
      dramatically enlarged by climbing fiber (CF)-dependent plasticity. To analyze the
      effects of this receptive field plasticity, we present for the first time whole
      cell patch-clamp recordings from these interneurons during natural and electrical
      activation of cutaneously driven synaptic input. In "naive" interneurons,
      peripheral input nearly exclusively activated a few (two to eight) large PF EPSPs
      from a specific small skin area that overlapped the receptive field of the local
      CF input. After conjunctive PF and CF stimulation, numerous small and large EPSPs
      and ramp-like depolarizations could be activated from the entire forelimb skin.
      These findings therefore confirm previous suggestions that conjunctive PF and CF
      activation leads to a long-lasting potentiation of PF synaptic input to
      interneurons. The CF response, which is crucial for the induction of the PF
      synaptic potentiation, was strong but variable and very different from the
      conventional EPSPs evoked by PFs.

PMID- 14573543
TI  - Dissociable contributions of the human amygdala and orbitofrontal cortex to
      incentive motivation and goal selection.
AB  - Theories of incentive motivation attempt to capture the way in which objects and
      events in the world can acquire high motivational value and drive behavior, even
      in the absence of a clear biological need. In addition, for an individual to
      select the most appropriate goal, the incentive values of competing desirable
      objects need to be defined and compared. The present study examined the neural
      substrates by which appetitive incentive value influences prospective goal
      selection, using positron emission tomographic neuroimaging in humans. Sated
      subjects were shown a series of restaurant menus that varied in incentive value,
      specifically tailored for each individual, and in half the trials, were asked to
      make a selection from the menu. The amygdala was activated by high-incentive
      menus regardless of whether a choice was required. Indeed, activity in this
      region varied as a function of individual subjective ratings of incentive value.
      In contrast, distinct regions of the orbitofrontal cortex were recruited both
      during incentive judgments and goal selection. Activity in the medial orbital
      cortex showed a greater response to high-incentive menus and when making a
      choice, with the latter activity also correlating with subjective ratings of
      difficulty. Lateral orbitofrontal activity was observed selectively when
      participants had to suppress responses to alternative desirable items to select
      their most preferred. Taken together, these data highlight the differential
      contribution of the amygdala and regions within the orbitofrontal cortex in a
      neural system underlying the selection of goals based on the prospective
      incentive value of stimuli, over and above homeostatic influences.

PMID- 14573544
TI  - Target-specific neuropeptide Y-ergic synaptic inhibition and its network
      consequences within the mammalian thalamus.
AB  - Neuropeptides are commonly colocalized with classical neurotransmitters, yet
      there is little evidence for peptidergic neurotransmission in the mammalian CNS.
      We performed whole-cell patch-clamp recording from rodent thalamic brain slices
      and repetitively stimulated corticothalamic fibers to strongly activate NPY
      containing GABAergic reticular thalamic (RT) neurons. This resulted in long
      lasting (approximately 10 sec) feedforward slow IPSPs (sIPSPs) in RT cells, which
      were mimicked and blocked by NPY1 (Y1) receptor agonists and antagonists,
      respectively, and were present in wild-type mice but absent in NPY-/- mice.
      NPYergic sIPSPs were mediated via G-proteins and G-protein-activated, inwardly
      rectifying potassium channels, as evidenced by sensitivity to GDP-beta-S and 0.1
      mm Ba2+. In rat RT neurons, NPYergic sIPSPs were also present but were
      surprisingly absent in the major synaptic targets of RT, thalamic relay neurons,
      where instead robust GABA(B) IPSPs occurred. In vitro oscillatory network
      responses in rat thalamus were suppressed and augmented by Y1 agonists and
      antagonists, respectively. These findings provide evidence for segregation of
      postsynaptic actions between two targets of RT cells and support a role for
      endogenously released NPY within RT in the regulation of oscillatory thalamic
      responses relevant to sleep and epilepsy.

PMID- 14573545
TI  - Ionic mechanisms of burst firing in dissociated Purkinje neurons.
AB  - Cerebellar Purkinje neurons have intrinsic membrane properties that favor burst
      firing, seen not only during complex spikes elicited by climbing fiber input but
      also with direct electrical stimulation of cell bodies. We examined the ionic
      conductances that underlie all-or-none burst firing elicited in acutely
      dissociated mouse Purkinje neurons by short depolarizing current injections.
      Blocking voltage-dependent calcium entry by cadmium or replacement of external
      calcium by magnesium enhanced burst firing, but it was blocked by cobalt
      replacement of calcium, probably reflecting block of sodium channels. In voltage
      clamp experiments, we used the burst waveform of each cell as a voltage command
      and used ionic substitutions and pharmacological manipulations to isolate
      tetrodotoxin (TTX)-sensitive sodium current, P-type and T-type calcium current,
      hyperpolarization-activated cation current (Ih), voltage-activated potassium
      current, large-conductance calcium-activated potassium current, and small
      conductance calcium-activated potassium (SK) current. Measured near the middle of
      the first interspike interval, TTX-sensitive sodium current carried the largest
      inward current, and T-type calcium current was also substantial. Current through
      P-type channels was large immediately after a spike but decayed rapidly. These
      inward currents were opposed by substantial components of voltage-dependent and
      calcium-dependent potassium current. Termination of the burst is caused partly by
      decay of sodium current, together with a progressive buildup of SK current after
      the first interspike interval. Although burst firing depends on the net balance
      between multiple large currents flowing after a spike, it is surprisingly robust,
      probably reflecting complex interactions between the exact voltage waveform and
      voltage and calcium dependence of the various currents.

PMID- 14573546
TI  - Major differences in inhibitory synaptic transmission onto two neocortical
      interneuron subclasses.
AB  - Locally projecting GABAergic interneurons are the major providers of inhibition
      in the neocortex and play a crucial role in several brain functions. Neocortical
      interneurons are connected via electrical and chemical synapses that may be
      crucial in modulating complex network oscillations. We investigated the
      properties of spontaneous and evoked IPSCs in two morphologically and
      physiologically identified interneuron subtypes, the fast-spiking (FS) and low
      threshold-spiking (LTS) cells in layer V of rodent sensorimotor cortex. We found
      that IPSCs recorded in FS cells were several orders of magnitude more frequent,
      larger in amplitude, and had faster kinetics than IPSCs recorded in LTS cells.
      GABA(A) receptor alpha- and beta-subunit selective modulators, zolpidem and
      loreclezole, had different effects on IPSCs in FS and LTS interneurons,
      suggesting differential expression of GABA(A) receptor subunit subtypes. These
      pharmacological data indicated that the alpha1 subunit subtype is poorly
      expressed by LTS cells but makes a large contribution to GABA(A) receptors on FS
      cells. This was confirmed by experiments performed in genetically modified mice
      in which the alpha1 subunit had been made insensitive to benzodiazepine-like
      agonists. These results suggest that differences in IPSC waveform are likely
      attributable to distinctive expression of GABA(A) receptor subunits in FS and LTS
      cells. The particular properties of GABAergic input on different interneuronal
      subtypes might have important consequences for generation and pacing of cortical
      rhythms underlying several brain functions. Moreover, selective pharmacological
      manipulation of distinct inhibitory circuits might allow regulation of pyramidal
      cell activities under specific physiological and pathophysiological conditions.

PMID- 14573548
TI  - Sleep deprivation causes behavioral, synaptic, and membrane excitability
      alterations in hippocampal neurons.
AB  - Although the function of sleep remains elusive, several lines of evidence suggest
      that sleep has an important role in learning and memory. In light of the
      available data and with the prevalence of sleep deprivation (SD), we sought to
      determine the effect of SD on neuronal functioning. We found that the exposure of
      rats to 72 hr of primarily rapid eye movement SD impaired their subsequent
      performance on a hippocampus-dependent spatial learning task but had no effect on
      an amygdala-dependent learning task. To determine the underlying cellular level
      mechanisms of this hippocampal deficit, we examined the impact of SD on several
      fundamental aspects of membrane excitability and synaptic physiology in
      hippocampal CA1 pyramidal neurons and dentate gyrus granule cells. We found that
      neuronal excitability was severely reduced in CA1 neurons but not in granule
      cells and that the production of long-term potentiation of synaptic strength was
      inhibited in both areas. Using multiple SD methods we further attempted to
      differentiate the effects of sleep deprivation from those associated with the
      nonspecific stress induced by the sleep deprivation methods. Together these data
      suggest that failure to acquire adequate sleep produces several molecular and
      cellular level alterations that profoundly inhibit hippocampal functioning.

PMID- 14573547
TI  - Fibroblast growth factor-inducible-14 is induced in axotomized neurons and
      promotes neurite outgrowth.
AB  - For successful nerve regeneration, a coordinated shift in gene expression pattern
      must occur in axotomized neurons. To identify genes participating in axonal
      regeneration, we characterized mRNA expression profiles in dorsal root ganglia
      (DRG) before and after sciatic nerve transection. Dozens of genes are
      differentially expressed after sciatic nerve injury by microarray analysis.
      Induction of SOX11, FLRT3, myosin-X, and fibroblast growth factor-inducible-14
      (Fn14) mRNA in axotomized DRG neurons was verified by Northern analysis and in
      situ hybridization. The Fn14 gene encodes a tumor necrosis-like weak inducer of
      apoptosis (TWEAK) receptor and is dramatically induced in DRG neurons after nerve
      damage, despite low expression in developing DRG neurons. Fn14 expression in PC12
      cells is also upregulated by nerve growth factor treatment. Overexpression of
      Fn14 promotes growth cone lamelipodial formation and increases neurite outgrowth
      in PC12 cells. These Fn14 effects are independent of the ligand, TWEAK. Fn14
      colocalizes with the Rho family GTPases, Cdc42 and Rac1. Furthermore, Fn14
      physically associates with Rac1 GTPase in immunoprecipitation studies. The
      neurite outgrowth-promoting effect of Fn14 is enhanced by Rac1 activation and
      suppressed by Rac1 inactivation. These findings suggest that Fn14 contributes to
      nerve regeneration via a Rac1 GTPase-dependent mechanism.

PMID- 14573549
TI  - Temperature-induced reciprocal activation of hippocampal field activity.
AB  - Hippocampal network activity oscillates between sustained rhythms (e.g., theta)
      and aperiodic population spikes (e.g., sharp waves, dentate spikes). Although
      temperature is known to modulate various aspects of rhythmic hippocampal
      activity, little is known regarding the influence of temperature on the incidence
      of population spikes. We recorded spontaneous hippocampal activity along the CA1
      dentate gyrus axis using multisite silicon electrodes in urethanized infant rats
      (P2-P16) at brain temperatures of 37 and 27 degrees C. Theta and gamma activity,
      as well as sharp waves, were detected at 37 degrees C but not at 27 degrees C. In
      contrast, dentate spikes were rare at 37 degrees C but their incidence increased
      several-fold at 27 degrees C (epileptiform activity also emerged at 27 degrees C
      in the oldest pups). This surprising increase in the incidence of dentate spike
      activity in a cold brain represents the first such demonstration for a neuronal
      field pattern. In addition, these findings indicate that changes in brain
      temperature produce systems-level shifts in the balance among reciprocally
      interacting hippocampal components.

PMID- 14573550
TI  - Direct physiological evidence for synaptic connectivity between medium-sized
      spiny neurons in rat nucleus accumbens in situ.
AB  - Dual whole cell patch-clamp recordings in rat nucleus accumbens, the main
      component of the ventral striatum, were made to assess the presence of synaptic
      interconnections between medium-sized spiny neurons, a group of GABAergic and
      peptidergic neurons that constitute the principal cells of the striatum. Neurons
      were stained with biocytin for subsequent morphological analysis. Electrical
      activity of cells was recorded in current- and voltage-clamp mode; the
      characteristics of medium-sized spiny neurons were confirmed by
      electrophysiological and morphological properties. Thirteen of 38 medium-sized
      spiny neuron pairs (34%) showed a synaptic connection. In these pairs,
      suprathreshold stimulation with current injection evoked a train of action
      potentials in the presynaptic cell, which in turn elicited depolarizing
      postsynaptic potentials (dPSPs) in the postsynaptic cell. Twelve of these 13
      pairs were connected unilaterally. The onset latency of the postsynaptic response
      was 1.7 +/- 0.7 ms. dPSPs were blocked by 12.5 microM bicuculline, suggesting
      they were mediated by GABA(A) receptors. A linear fit of the current-voltage
      relationship of GABAergic currents crossed the voltage axis near the value of -20
      mV, in agreement with the Cl(-) equilibrium potential predicted from the
      composition of the artificial cerebrospinal fluid and pipette medium. No evidence
      for electrotonic coupling was found. Paired-pulse facilitation and depression
      were induced when the amplitude of the first IPSC of a pair was relatively small
      and large, respectively. No clear dependence of paired-pulse facilitation or
      depression was found on the width of the spike interval, which ranged between 100
      and 380 ms. Conversely, 1- to 2-s trains of dPSPs showed marked frequency
      facilitation at low presynaptic frequencies, but frequency depression at high
      firing rates. These data show that intra-accumbens synaptic communication between
      medium-sized spiny neurons exists, is mediated by GABA(A) receptors, and exhibits
      spike train-dependent short-term dynamics.

PMID- 14573551
TI  - GABA neurotransmission in the cerebellar interposed nuclei: involvement in
      classically conditioned eyeblinks and neuronal activity.
AB  - The cerebellar interposed nuclei (IN) are an essential part of circuits that
      control classically conditioned eyeblinks in the rabbit. The function of the IN
      is under the control of GABAergic projections from Purkinje cells of the
      cerebellar cortex. The exact involvement of cerebellar cortical input into the IN
      during eyeblink expression is not clear. While it is known that the application
      of gamma-aminobutyric acid-A (GABA(A)) agonists and antagonists affects the
      performance of classically conditioned eyeblinks, the effects of these drugs on
      IN neurons in vivo are not known. The purpose of the present study was to measure
      the effects of muscimol and picrotoxin on the expression of conditioned eyeblinks
      and the activity of IN cells simultaneously. Injections of muscimol abolished
      conditioned responses and either silenced or diminished the activity of IN cells.
      Two injections were administered in each picrotoxin experiment. The first
      injection of picrotoxin slightly modified the timing and amplitude of the
      eyeblink, produced mild tonic eyelid closure, increased tonic activity of IN
      cells, and reduced the amplitude of the neural responses. The second injection of
      picrotoxin abolished conditioned responses, further increased tonic eyelid
      closure, dramatically elevated the tonic activity of IN cells, and in most cases,
      abolished neuronal responses. These results demonstrate that both GABA(A)
      mediated inactivation and tonic up-regulation of IN cells can interrupt the
      expression of conditioned eyeblinks and that this behavioral effect is
      accompanied by the suppression of the neuronal activity correlates of the
      conditioned stimulus and response.

PMID- 14573552
TI  - Involvement of human thalamic neurons in internally and externally generated
      movements.
AB  - Several anatomical studies support the existence of recurrent neural pathways
      from cortical motor areas to the thalamus via basal ganglia and back to the
      cortex. Neuronal responses to internally and externally generated sequential
      movements have been studied in the motor and premotor cortex of monkeys, but the
      involvement of subcortical motor structures such as the thalamus have not been
      studied in monkeys or humans. We examined the activity of neurons during a
      sequential button press task in motor thalamus of parkinsonian as well as chronic
      pain patients undergoing implantation of deep brain stimulating electrodes.
      Single and dual microelectrode recordings were carried out during an internally
      generated task with a memorized sequence (MEM) and an externally driven task with
      the sequence given during task performance (follow). Average histograms of
      neuronal firing were constructed for each task and aligned with respect to visual
      cues (ready, go) or button presses (P1, P2, P3). Sequential movements were
      monitored with surface electromyography and hand accelerometry, and cell
      responses were divided into movement-defined epochs for ANOVA and post hoc means
      testing. Of 52 neurons tested, 31 were found to have task-related responses and
      10 were task-selective with 4 responding preferentially to MEM and 7 responding
      preferentially to follow (1 was both). Complex responses were found including
      preparatory, delay period, and phase- and task-specific activity. These kinds of
      responses suggest a role of the thalamus in both internally and externally cued
      arms movement and provide some evidence for a role in sequential movements.

PMID- 14573553
TI  - Short duty cycle destabilizes a half-center oscillator, but gap junctions can
      restabilize the anti-phase pattern.
AB  - Mutually inhibitory pacemaker neurons with duty cycle close to 50% operate as a
      half-center oscillator (anti-phase coordination, i.e., 180 degrees out of phase),
      even in the presence of weak to modest gap junctional coupling. For electrical
      coupling strength above a critical value synchronization occurs. But, as shown
      here with modeling studies, the effects of electrical coupling depend critically
      on a cell's duty cycle. Instead of oscillating either in-phase or anti-phase,
      model cells with short duty cycle express additional rhythmic patterns, and
      different transitions between them, depending on electrical coupling strength.
      For weak or no electrical coupling, cells do not oscillate in anti-phase but
      instead exhibit almost in-phase activity. Strengthening this weak coupling leads
      to stable anti-phase activity. With yet stronger electrical coupling stable
      inphase (synchrony) emerges but it coexists with the anti-phase pattern. Thus the
      network shows bistability for an intermediate range of coupling strength. For
      sufficiently strong electrical coupling synchrony is the network's only
      attracting rhythmic state. Our results, numerical and analytical (phase plane
      analysis), are based on a minimal but biophysically motivated pacemaker model for
      the slowly oscillating envelope of bursting neurons. However, illustrations for
      an Hodgkin-Huxley model suggest that some of our results for short duty cycle may
      extend to patterning of repetitive spikes. In particular, electrical coupling of
      intermediate strength may promote anti-phase activity and provide bistability of
      anti-phase and in-phase spiking.

PMID- 14573554
TI  - Riluzole-sensitive slowly inactivating sodium current in rat suprachiasmatic
      nucleus neurons.
AB  - The persistent (i.e., slowly inactivating) fraction of the Na current (I(Na,P))
      regulates excitability of CNS neurons. In isolated rat suprachiasmatic nucleus
      (SCN) neurons with a ramp-type voltage-clamp protocol, we have studied the
      properties of a robust current that has the general properties of I(Na,P) but
      exhibits a slow inactivation (I(Na,S)). The time dependence of the development of
      the inactivation was also studied by clamping of the membrane potential at
      different levels: time constants ranging from approximately 50 to approximately
      700 ms, depending on the voltage level, were revealed. The I(Na,S) (50-150 pA)
      was present in both spontaneously active and silent neurons. The neurons
      exhibited I(Na,S) without visible rundown during approximately 1-h recordings.
      I(Na,S) had a threshold between -65 and -60 mV and was maximal at about -45 mV.
      Tetrodotoxin (TTX; 1 microM) completely and reversibly blocked I(Na,S). Riluzole,
      an effective blocker of I(Na,P), inhibited reversibly I(Na,S) with an EC(50) of 1
      2 microM. Microapplication of 10 microM riluzole during either extracellular or
      intracellular recording suppressed spontaneous activity in isolated SCN neurons.
      In the slice preparation, bath application of 20 microM riluzole resulted in
      decreased firing rate or complete suppression of spontaneous activity in some
      neurons (9/14) but had no effect on other neurons (5/14). In riluzole-resistant
      neurons in cell-attached experiments, low-amplitude current spikes were present
      in 1 microM TTX. We concluded that I(Na,S) is ubiquitously expressed by all SCN
      neurons and that this current is a necessary but not sufficient depolarizing
      component of the mechanism for spontaneous firing.

PMID- 14573555
TI  - Median and dorsal raphe neurons are not electrophysiologically identical.
AB  - The dorsal (DR) and median raphe (MR) nuclei contain 5-hydroxytryptamine
      (serotonin, 5-HT) cell bodies that give rise to the majority of the ascending 5
      HT projections to the forebrain limbic areas that control emotional behavior. In
      the past, the electrophysiological identification of neurochemically identified 5
      HT neurons has been limited. Recent technical developments have made it possible
      to re-examine the electrophysiological characteristics of identified 5-HT- and
      non-5-HT-containing neurons. Visualized whole cell electrophysiological
      techniques in combination with fluorescence immunohistochemistry for 5-HT were
      used. In the DR, both 5-HT- and non-5-HT-containing neurons exhibited similar
      characteristics that have historically been attributed to putative 5-HT neurons.
      In contrast, in the MR, the 5-HT-and non-5-HT-containing neurons had very
      different characteristics. Interestingly, the MR 5-HT-containing neurons had a
      shorter time constant and larger afterhyperpolarization (AHP) amplitude than DR 5
      HT-containing neurons. The 5-HT(1A) receptor-mediated response was also measured.
      The efficacy of the response elicited by 5-HT(1A) receptor activation was greater
      in 5-HT-containing neurons in the DR than the MR, whereas the potency was
      similar, implicating greater autoinhibition in the DR. Non-5-HT-containing
      neurons in the DR were responsive to 5-HT(1A) receptor activation, whereas the
      non-5-HT-containing neurons in the MR were not. These differences in the cellular
      characteristics and 5-HT(1A) receptor-mediated responses between the MR and DR
      neurons may be extremely important in understanding the role of these two 5-HT
      circuits in normal physiological processes and in the etiology and treatment of
      pathophysiological states.

PMID- 14573557
TI  - What the brain stem tells the frontal cortex. II. Role of the SC-MD-FEF pathway
      in corollary discharge.
AB  - One way we keep track of our movements is by monitoring corollary discharges or
      internal copies of movement commands. This study tested a hypothesis that the
      pathway from superior colliculus (SC) to mediodorsal thalamus (MD) to frontal eye
      field (FEF) carries a corollary discharge about saccades made into the
      contralateral visual field. We inactivated the MD relay node with muscimol in
      monkeys and measured corollary discharge deficits using a double-step task: two
      sequential saccades were made to the locations of briefly flashed targets. To
      make second saccades correctly, monkeys had to internally monitor their first
      saccades; therefore deficits in the corollary discharge representation of first
      saccades should disrupt second saccades. We found, first, that monkeys seemed to
      misjudge the amplitudes of their first saccades; this was revealed by systematic
      shifts in second saccade end points. Thus corollary discharge accuracy was
      impaired. Second, monkeys were less able to detect trial-by-trial variations in
      their first saccades; this was revealed by reduced compensatory changes in second
      saccade angles. Thus corollary discharge precision also was impaired. Both
      deficits occurred only when first saccades went into the contralateral visual
      field. Single-saccade generation was unaffected. Additional deficits occurred in
      reaction time and overall performance, but these were bilateral. We conclude that
      the SC-MD-FEF pathway conveys a corollary discharge used for coordinating
      sequential saccades and possibly for stabilizing vision across saccades. This
      pathway is the first elucidated in what may be a multilevel chain of corollary
      discharge circuits extending from the extraocular motoneurons up into cerebral
      cortex.

PMID- 14573556
TI  - Two distinct types of noisy oscillators in electroreceptors of paddlefish.
AB  - Our computational analyses and experiments demonstrate that ampullary
      electroreceptors in paddlefish (Polyodon spathula) contain 2 distinct types of
      continuously active noisy oscillators. The spontaneous firing of afferents
      reflects both rhythms, and as a result is stochastically biperiodic
      (quasiperiodic). The first type of oscillator resides in the sensory epithelia,
      is recorded as approximately 26 Hz and +/-70 microV voltage fluctuations at the
      canal skin pores, and gives rise to a noisy peak at f(e) approximately 26 Hz in
      power spectra of spontaneous afferent firing. The second type of oscillator
      resides in afferent terminals, is seen as a noisy peak at f(a) approximately 30
      70 Hz that dominates the power spectra of spontaneous afferent firing, and
      corresponds to the mean spontaneous firing rate. Sideband peaks at frequencies of
      f(a) +/- f(e) are consistent with epithelia-to-afferent unidirectional synaptic
      coupling or, alternatively, nonlinear mixing of the 2 oscillatory processes.
      External stimulation affects the frequency of only the afferent oscillator, not
      the epithelial oscillators. Application of temperature gradients localized the
      f(e) and f(a) oscillators to different depths below the skin. Having 2 distinct
      types of internal oscillators is a novel form of organization for peripheral
      sensory receptors, of relevance for other hair cell sensory receptors.

PMID- 14573558
TI  - What the brain stem tells the frontal cortex. I. Oculomotor signals sent from
      superior colliculus to frontal eye field via mediodorsal thalamus.
AB  - Neuronal processing in cerebral cortex and signal transmission from cortex to
      brain stem have been studied extensively, but little is known about the numerous
      feedback pathways that ascend from brain stem to cortex. In this study, we
      characterized the signals conveyed through an ascending pathway coursing from the
      superior colliculus (SC) to the frontal eye field (FEF) via mediodorsal thalamus
      (MD). Using antidromic and orthodromic stimulation, we identified SC source
      neurons, MD relay neurons, and FEF recipient neurons of the pathway in Macaca
      mulatta. The monkeys performed oculomotor tasks, including delayed-saccade tasks,
      that permitted analysis of signals such as visual activity, delay activity, and
      presaccadic activity. We found that the SC sends all of these signals into the
      pathway with no output selectivity, i.e., the signals leaving the SC resembled
      those found generally within the SC. Visual activity arrived in FEF too late to
      contribute to short-latency visual responses there, and delay activity was
      largely filtered out in MD. Presaccadic activity, however, seemed critical
      because it traveled essentially unchanged from SC to FEF. Signal transmission in
      the pathway was fast ( approximately 2 ms from SC to FEF) and topographically
      organized (SC neurons drove MD and FEF neurons having similarly eccentric visual
      and movement fields). Our analysis of identified neurons in one pathway from
      brain stem to frontal cortex thus demonstrates that multiple signals are sent
      from SC to FEF with presaccadic activity being prominent. We hypothesize that a
      major signal conveyed by the pathway is corollary discharge information about the
      vector of impending saccades.

PMID- 14573559
TI  - Detailed model of intersegmental coordination in the timing network of the leech
      heartbeat central pattern generator.
AB  - To address the general problem of intersegmental coordination of oscillatory
      neuronal networks, we have studied the leech heartbeat central pattern generator.
      The core of this pattern generator is a timing network that consists of two
      segmental oscillators, each of which comprises two identified, reciprocally
      inhibitory oscillator interneurons. Intersegmental coordination between the
      segmental oscillators is mediated by synaptic interactions between the oscillator
      interneurons and identified coordinating interneurons. The small number of
      neurons (8) and the distributed structure of the timing network have made the
      experimental analysis of the segmental oscillators as discrete, independent units
      possible. On the basis of this experimental work, we have made conductance-based
      models to explore how intersegmental phase and cycle period are determined. We
      show that although a previous simple model, which ignored many details of the
      living system, replicated some essential features of the living system, the
      incorporation of specific cellular and network properties is necessary to capture
      the behavior of the system seen under different experimental conditions. For
      example, spike frequency adaptation in the coordinating interneurons and details
      of asymmetries in intersegmental connectivity are necessary for replicating
      driving experiments in which one segmental oscillator was injected with periodic
      current pulses to entrain the activity of the entire network. Nevertheless, the
      basic mechanisms of phase and period control demonstrated here appear to be very
      general and could be used by other networks that produce coordinated segmental
      motor outflow.

PMID- 14573560
TI  - Organization of action sequences and the role of the pre-SMA.
AB  - To understand the contribution of the human presupplementary motor area (pre-SMA)
      in sequential motor behavior, we performed a series of finger key-press
      experiments. Experiment 1 revealed that each subject had a spontaneous tendency
      to organize or "chunk" a long sequence into shorter components. We hypothesized
      that the pre-SMA might have a special role in initiating each chunk but not at
      other points during the sequence. Experiment 2 therefore examined the effect of
      0.5-s, 10-Hz repetitive transcranial magnetic stimulation (rTMS) directed over
      the pre-SMA. As hypothesized, performance was disrupted when rTMS was delivered
      over the pre-SMA at the beginning of the second chunk but not when it was
      delivered in the middle of a chunk. Contrary to the hypothesis, TMS did not
      disrupt sequence initiation. Experiments 3 and 4 examined whether the very first
      movement of a sequence could be disrupted under any circumstances. Pre-SMA TMS
      did disrupt the initiation of sequences but only when subjects had to switch
      between sequences and when the first movement of each sequence was not covertly
      instructed by a learned visuomotor association. In conjunction, the results
      suggest that for overlearned sequences the pre-SMA is primarily concerned with
      the initiation of a sequence or sequence chunk and the role of the pre-SMA in
      sequence initiation is only discerned when subjects must retrieve the sequence
      from memory as a superordinate set of movements without the aid of a visuomotor
      association. Control experiments revealed such effects were not present when rTMS
      was applied over the left dorsal premotor cortex.

PMID- 14573561
TI  - Microstimulation in the region of the human thalamic principal somatic sensory
      nucleus evokes sensations like those of mechanical stimulation and movement.
AB  - We explored the region of human thalamic somatic sensory nucleus (ventral caudal,
      Vc), corresponding to monkey ventral posterior (VP), with threshold
      microstimulation (TMIS) during stereotactic procedures for the treatment of
      tremor. Of 122 sites in 116 patients (124 thalami) where mechanical (touch,
      pressure, and sharp) or movement [movement through the body (movement) and
      vibration] sensations were evoked, 72 sites were found in the core or in adjacent
      regions, posterior-inferior (33), inferior (4), and posterior to the core (13).
      Sites where TMIS evoked touch were less frequently found in the core than those
      where movement or pressure sensations were evoked. Pressure was more commonly (P
      < 0.05) evoked than vibration at sites where cells had intraoral receptive fields
      (RFs). Touch and vibration were more commonly (P < 0.05) evoked than pressure at
      sites where cells had facial RFs, consistent with the relative density of rapidly
      adapting (RA) receptors in the mouth and face. Sites described as deep and
      movement were found superior and anterior in the core, consistent with the
      location of cells responding to stimulation of muscle afferents. At 72 of 122
      sites, TMIS evoked the same sensation at two or more sites in the same plane. Of
      these sites, 58 are adjacent to each other, in a cluster, consistent with studies
      of the localization of cells responding to different modalities. These results
      demonstrate that mechanical and movement sensations can be evoked by stimulation
      in the region of Vc. The characteristics of these sites suggest that the
      sensations are evoked by stimulation of pathways specific to cutaneous and deep
      mechanoreceptors.

PMID- 14573562
TI  - Neurons synthesizing melanin-concentrating hormone identified by selective
      reporter gene expression after transfection in vitro: transmitter responses.
AB  - Neurons from the lateral hypothalamus that synthesize melanin-concentrating
      hormone (MCH) play an important role in the regulation of energy homeostasis.
      Relatively little is known of the cellular physiology and transmitter responses
      of these neurons, in part because of the difficulty in identifying live MCH
      cells. Here we use a novel approach of transfection of specific gene constructs
      with the MCH promoter driving green fluorescent protein (GFP) or red fluorescent
      protein (dsRed2) in CNS cultures to identify live rat MCH neurons; all neurons
      expressing the reporter gene showed MCH immunoreactivity, indicating selective
      expression. MCH neurons had a resting membrane potential of -57.5 +/- 0.6 mV, a
      linear current-voltage relation and a mean input resistance of 1,013 MOmega. Long
      depolarizing pulses revealed significant spike frequency adaptation. Functional
      glutamate and GABA receptors were expressed by MCH neurons. MCH neurons were
      hyperpolarized by norepinephrine in the presence or absence of tetrodotoxin,
      suggesting direct inhibition. Orexigenic peptides neuropeptide Y (NPY) and MCH
      showed no direct effect on membrane potential, input resistance, action potential
      width, or afterhyperpolarization potential, but inhibited voltage-dependent
      calcium channels, indicating that MCH neurons expressed both MCH and NPY
      receptors.

PMID- 14573564
TI  - Sydney's school photos.

PMID- 14573563
TI  - Novel form of long-term synaptic depression in rat hippocampus induced by
      activation of alpha 1 adrenergic receptors.
AB  - Neurons located in the locus coeruleus project to hippocampus and provide
      noradrenergic innervation necessary for hippocampal-dependent learning and
      memory. The mechanisms underlying the function of norepinephrine (NE) in memory
      processing are unknown but likely reside in the ability of NE to modulate the
      efficacy of glutamate synaptic transmission via activation of G-protein-coupled
      adrenergic receptors. Here we show that application of NE to rat hippocampal
      slices in vitro induces a long-term depression (LTD) of synaptic transmission at
      excitatory CA3-CA1 synapses that persists for >/=40 min after agonist washout.
      This LTD, which we refer to as NE LTD, is mediated by activation of alpha1
      adrenergic receptors because the alpha1 agonist methoxamine can induce LTD at the
      same magnitude as that induced with the nonselective adrenergic agonist NE.
      Furthermore, NE LTD induced by either NE or methoxamine is blocked with the
      alpha1 receptor antagonist, prazosin, but is unaffected by antagonists of alpha2
      and beta receptors. This plasticity persists in the presence of the GABA(A)
      receptor antagonist bicuculline, indicating that adrenergic modulation of GABA(A)
      receptor-mediated transmission does not underlie NE LTD. Induction of NE LTD
      requires presynaptic activity during agonist application and postsynaptic
      activation of N-methyl-d-aspartate receptors, fulfilling Hebbian criteria of
      coincident pre- and postsynaptic activity. The expression of NE LTD is likely to
      be postsynaptic because paired-pulse facilitation ratios during NE LTD expression
      are not different from baseline, similar to LTD induced by low-frequency
      stimulation. Thus we report the identification and characterization of a novel
      Hebbian form of LTD in hippocampus that is induced after activation of alpha1
      adrenergic receptors. This plasticity may be a mechanism by which the adrenergic
      system participates in normal cognitive function.

PMID- 14573565
TI  - Weather, climate, and public health.

PMID- 14573566
TI  - Iraqi reconstruction: for an empowerment process.

PMID- 14573567
TI  - Whose health is it anyway?: enabling participation.

PMID- 14573568
TI  - Shoes and lower limb osteoarthritis.

PMID- 14573569
TI  - Monitoring the severe acute respiratory syndrome epidemic and assessing
      effectiveness of interventions in Hong Kong Special Administrative Region.
AB  - OBJECTIVE: To estimate the infection curve of severe acute respiratory syndrome
      (SARS) using the back projection method and to assess the effectiveness of
      interventions. DESIGN: Statistical method. DATA: The daily reported number of
      SARS and interventions taken by Hong Kong Special Administrative Region (HKSAR)
      up to 24 June 2003 are used. METHOD: To use a back projection technique to
      construct the infection curve of SARS in Hong Kong. The estimated epidemic curve
      is studied to identify the major events and to assess the effectiveness of
      interventions over the course of the epidemic. RESULTS: The SARS infection curve
      in Hong Kong is constructed for the period 1 March 2003 to 24 June 2003. Some
      interventions seem to be effective while others apparently have little or no
      effect. The infections among the medical and health workers are high.
      CONCLUSIONS: Quarantine of the close contacts of confirmed and suspected SARS
      cases seems to be the most effective intervention against spread of SARS in the
      community. Thorough disinfection of the infected area against environmental
      hazards is helpful. Infections within hospitals can be reduced by better
      isolation measures and protective equipments.

PMID- 14573570
TI  - Host and environment are key factors.

PMID- 14573571
TI  - Virus pathogens suggest an autumn return.

PMID- 14573572
TI  - Sporadic contact with unfamiliar source makes epidemic unlikely.

PMID- 14573573
TI  - Identification and control are the priority.

PMID- 14573574
TI  - Future outbreaks will be less dramatic.

PMID- 14573575
TI  - Vigorous controls minimise risk.

PMID- 14573576
TI  - Avoid complacency--prepare for the worst.

PMID- 14573577
TI  - Out of the woods or in the eye of the storm?

PMID- 14573578
TI  - Learn from influenza epidemiology.

PMID- 14573579
TI  - Life course epidemiology.

PMID- 14573580
TI  - Understanding the functional components of public health surveillance.

PMID- 14573582
TI  - Cold related mortality in England and Wales; influence of social class in working
      and retired age groups.

PMID- 14573581
TI  - Excess winter mortality in Europe: a cross country analysis identifying key risk
      factors.
AB  - OBJECTIVE: Much debate remains regarding why certain countries experience
      dramatically higher winter mortality. Potential causative factors other than cold
      exposure have rarely been analysed. Comparatively less research exists on excess
      winter deaths in southern Europe. Multiple time series data on a variety of risk
      factors are analysed against seasonal-mortality patterns in 14 European countries
      to identify key relations Subjects and setting: Excess winter deaths (all
      causes), 1988-97, EU-14. DESIGN: Coefficients of seasonal variation in mortality
      are calculated for EU-14 using monthly mortality data. Comparable, longitudinal
      datasets on risk factors pertaining to climate, macroeconomy, health care,
      lifestyle, socioeconomics, and housing were also obtained. Poisson regression
      identifies seasonality relations over time. RESULTS: Portugal suffers from the
      highest rates of excess winter mortality (28%, CI=25% to 31%) followed jointly by
      Spain (21%, CI=19% to 23%), and Ireland (21%, CI=18% to 24%). Cross country
      variations in mean winter environmental temperature (regression coefficient
      (beta)=0.27), mean winter relative humidity (beta=0.54), parity adjusted per
      capita national income (beta=1.08), per capita health expenditure (beta=-1.19),
      rates of income poverty (beta=-0.47), inequality (beta=0.97), deprivation
      (beta=0.11), and fuel poverty (beta=0.44), and several indicators of residential
      thermal standards are found to be significantly related to variations in relative
      excess winter mortality at the 5% level. The strong, positive relation with
      environmental temperature and strong negative relation with thermal efficiency
      indicate that housing standards in southern and western Europe play strong parts
      in such seasonality. CONCLUSIONS: High seasonal mortality in southern and western
      Europe could be reduced through improved protection from the cold indoors,
      increased public spending on health care, and improved socioeconomic
      circumstances resulting in more equitable income distribution.

PMID- 14573583
TI  - Alice Hamilton, MD: gaining visibility for industrial medicine.

PMID- 14573584
TI  - Labour market income inequality and mortality in North American metropolitan
      areas.
AB  - OBJECTIVE: To investigate relations between labour market income inequality and
      mortality in North American metropolitan areas. METHODS: An ecological cross
      sectional study of relations between income inequality and working age (25-64
      years) mortality in 53 Canadian (1991) and 282 US (1990) metropolitan areas using
      four measures of income inequality. Two labour market income concepts were used:
      labour market income for households with non-trivial attachment to the labour
      market and labour market income for all households, including those with zero and
      negative incomes. Relations were assessed with weighted and unweighted bivariate
      and multiple regression analyses. RESULTS: US metropolitan areas were more
      unequal than their Canadian counterparts, across inequality measures and income
      concepts. The association between labour market income inequality and working age
      mortality was robust in the US to both the inequality measure and income concept,
      but the association was inconsistent in Canada. Three of four inequality measures
      were significantly related to mortality in Canada when households with zero and
      negative incomes were included. In North American models, increases in earnings
      inequality were associated with hypothetical increases in working age mortality
      rates of between 23 and 33 deaths per 100 000, even after adjustment for median
      metropolitan incomes. CONCLUSIONS: This analysis of labour market inequality
      provides more evidence regarding the robust nature of the relation between income
      inequality and mortality in the US. It also provides a more refined understanding
      of the nature of the relation in Canada, pointing to the role of unemployment in
      generating Canadian metropolitan level health inequalities.

PMID- 14573585
TI  - Socioeconomic status and tobacco expenditure among Australian households: results
      from the 1998-99 Household Expenditure Survey.
AB  - OBJECTIVE: To investigate the relation between socioeconomic status (SES) and
      tobacco expenditure among Australian households. DESIGN AND SETTING: Cross
      sectional study (The Household Expenditure Survey 1998-99) by the Australian
      Bureau of Statistics, based on a multi-stage national sample of 9682 households.
      PARTICIPANTS: From selected households, all members aged 15 and over were
      interviewed. MAIN RESULTS: Lower SES was associated with higher odds of reporting
      tobacco expenditure. Among smoking households, those from lower SES spent more of
      their funds on tobacco. For example, households headed by a person with no
      educational qualification spent 34% more on tobacco than those headed by a person
      with a university degree. Blue collar households spent 23% more than professional
      households. Percentage of total household expenditure on tobacco in the first
      income quintile was 62% more than that of households in the fifth quintile.
      CONCLUSION: Antismoking interventions and policies that are specifically aimed at
      lower SES groups can potentially improve social equality. They can also
      ameliorate social inequalities in health, given that much of the SES
      differentials in morbidity and mortality are attributed to the pronounced SES
      gradient in smoking.

PMID- 14573586
TI  - Socioeconomic status over the life course and stages of cigarette use:
      initiation, regular use, and cessation.
AB  - STUDY OBJECTIVE: To investigate the association between multiple indicators of
      socioeconomic status (SES) over the life course and three stages of cigarette
      use: initiation, regular use, and cessation. DESIGN: Prospective birth cohort
      study. SETTING: Providence, Rhode Island. PARTICIPANTS: Subjects (n=657) aged 30
      to 39 were offspring of participants in the Brown University cohort of the United
      States National Collaborative Perinatal Project started in 1959. MAIN RESULTS: A
      significantly increased risk of smoking initiation was observed among people from
      lower socioeconomic backgrounds. Low SES in childhood also increased the risk for
      progression to regular smoking, and was associated with a reduced likelihood of
      smoking cessation. Progression to regular smoking and smoking persistence were
      also associated with lower adult SES. CONCLUSIONS: Socioeconomic conditions over
      the life course accumulate to produce increased rates of smoking uptake and
      reduced rates of cessation among lower SES people. Addressing SES gradients in
      smoking will require persistent and extended intervention over multiple life
      stages.

PMID- 14573588
TI  - Women brothel workers and occupational health risks.
AB  - STUDY OBJECTIVES: This study examined working conditions, reported morbidity,
      symptoms of post-traumatic stress disorder (PTSD) and depression and their
      relation to an index of occupational health risk among women working in brothels
      in Israel. DESIGN: Personal structured interviews with a scale of occupational
      risk that included seven self report items reflecting past and present morbidity
      and symptoms. PARTICIPANTS AND SETTING: A purposive sample of 55 women in three
      cities in Israel, between the ages of 18-38. MAIN RESULTS: Most (82%) women were
      trafficked into Israel to work illegally in prostitution, effectively deriving
      them of access to discretionary health care. A third of the sample (32%) had a
      high score (between 3 to 6) on the index of occupational risk factors. A high
      score was not related to recent physician or gynaecological visits and was more
      common among illegal workers than those with residence status. A set of
      regression analyses showed that the most significant predictors of reporting a
      high level of occupational risk symptoms were starting sex work at an early age,
      the number of hours worked in a day, a history of suicide attempts and PTSD
      symptoms. CONCLUSIONS: High occupational risk was found to be unrelated to recent
      physician or gynaecological visits, indicating that these visits were most
      probably controlled by the brothel owners and not by medical need as perceived by
      the women themselves. Furthermore, occupational risk factors were associated with
      some of the working and background conditions reported by women brothel workers.
      There is an urgent need for medical care for this high risk group.

PMID- 14573589
TI  - Central and total obesity in middle aged men and women in relation to lifetime
      socioeconomic status: evidence from a national birth cohort.
AB  - STUDY OBJECTIVE: To investigate the influence of social class in childhood, young
      adulthood and middle age, and intergenerational mobility, on adult central and
      total obesity. DESIGN: Prospective, population based, birth cohort study.
      PARTICIPANTS AND SETTING: 1472 men and 1563 women born in 1946 in England,
      Scotland, and Wales. OUTCOME MEASURES: Waist-hip ratio, waist-height ratio, waist
      circumference, and body mass index at age 53 years. MAIN RESULTS: Father's social
      class at participant's age 4 years was inversely associated with adult central
      and total obesity at age 53 years in men and women. For example, the mean
      difference of waist-hip ratio (95% confidence intervals) between father's
      professional social class I and unskilled manual social class V was 2.6% (0.7 to
      4.6) for men and 2.5% (0.5 to 4.4) for women. The effect of father's social class
      remained after adjustment for participant's own social class in young adulthood
      and middle age. Both adult social classes were inversely related to obesity among
      women, but not men, after adjustment for childhood circumstances. Upwardly mobile
      men and women were less obese than participants remaining in their father's
      social class and their levels of obesity tended to be between the class they left
      and the class they joined. CONCLUSIONS: The effect of social class on adult
      obesity differed according to the stage in the life course at which social class
      was measured, and gender. Childhood circumstances had enduring influences on
      adult obesity, although our results on intergenerational mobility indicate
      potential reversibility of early life disadvantage.

PMID- 14573590
TI  - An investigation of risk factors for symptomatic osteoarthritis of the knee in
      women using a life course approach.
AB  - STUDY OBJECTIVE: To explore risk factors for symptomatic knee osteoarthritis
      (OAK) in women, which included wearing high heeled shoes. DESIGN: Matched case
      control study. Exposure information obtained by interview, included details about
      past footwear. Self reported weight and height data obtained representing when
      women left school, were aged 36-40 and were aged 51-55. Regular work activities
      (including periods when homemaker or carer), smoking, and hormone related data
      gathered using a life-grid. SETTING: Interviews in participants' homes. Cases
      identified from orthopaedic hospital surgical waiting list, controls identified
      by general practitioners (GPs) PARTICIPANTS: Women aged 50 to 70 years. Cases
      awaiting knee replacement surgery. Controls, who had no past knee surgery and no
      knee pain in the past three years, were matched for age and GP. Altogether 111
      eligible women were interviewed (29 cases, 82 controls). MAIN RESULTS: Univariate
      analyses identified several significant associations with OAK including past knee
      injury, arthritis of the feet, heavy smoking, being overweight (BMI 25 or above)
      and various occupational activities. Virtually all measures of high heeled shoes
      use were associated with reduced risk of OAK, although none of these findings
      were statistically significant. In multivariate analysis only BMI 25 or above at
      age 36-40 remained significantly associated with OAK (OR 36.4, 95% CI 3.07 to
      432, p=0.004), although weak evidence suggested certain occupational activities
      might increase risk. Weight gain in early adult life was particularly pronounced
      among cases. CONCLUSIONS: Being overweight before the age of 40 considerably
      increased the risk of subsequent symptomatic OAK in women. Wearing high heeled
      shoes did not.

PMID- 14573591
TI  - A simple approximate mathematical model to predict the number of severe acute
      respiratory syndrome cases and deaths.
AB  - BACKGROUND: Severe acute respiratory syndrome (SARS) is currently spreading in
      many countries. This paper proposes a simple approximate mathematical model for
      public health practitioners to predict the number of SARS cases and deaths.
      METHODS: The model is based on four parameters: R(o) (basic reproductive number),
      F (case-fatality rate), i (incubation period), and d (duration of disease). The
      calculations can be done by hand or by using a computer spreadsheet. RESULTS: The
      best parameters to fit Canadian data as of 6 April 2003 (before infection
      controls took effect) are R(o) = 1.5, F = 30%, i = 5 days, d = 14 days. On 6
      April (day 40) there were 74 cases and 7 deaths. If this trend continues, SARS
      numbers in Canada are predicted to be as follows: 387 cases and 34 deaths by 26
      April (day 60), 4432 cases and 394 deaths by 26 May (day 90), and 50 500 cases
      and 4489 deaths by 25 June (day 120). By comparison, the best parameters to fit
      Hong Kong data as of 10 April 2003 are R(o) = 2.0, F = 20%, i = 5 days, d = 14
      days. CONCLUSIONS: Using the proposed mathematical model, it was estimated that
      about 1.5 to 2 new infectious cases were produced per infectious case every five
      days. Also, about 20% to 30% of the cases die within 14 days. The case-fatality
      may therefore be considerably higher than initially thought. The model indicates
      that SARS can spread very fast when there are no interventions.

PMID- 14573592
TI  - Small-angle X-ray scattering-based three-dimensional reconstruction of the
      immunogen KLH1 reveals different oxygen-dependent conformations.
AB  - For decades the respiratory protein keyhole limpet hemocyanin (KLH1) from the
      marine gastropod Megathura crenulata has been used widely as a potent
      immunostimulant, useful hapten carrier, and valuable agent in the treatment of
      bladder carcinoma. Although much information on the immunological properties of
      KLH1 is available, biochemical and structural data are still incomplete. Small
      angle x-ray scattering revealed the existence of two conformations, an oxy state
      being slightly more compact than the deoxy state. Based on small-angle scattering
      curves, a newly developed Monte Carlo algorithm delivered a surface
      representation of proteins. The massive changes of the surfaces of reconstructed
      didecameric KLH1 molecules are explained as a twist of the two non-covalently
      associated decameric half-molecules. Upon oxygenation, the KLH1 molecule becomes
      longer and skinnier. This study provides the first real evidence how a molluscan
      hemocyanin changes conformation during an allosteric transition.

PMID- 14573593
TI  - Neuropeptide-induced transactivation of a neuronal epidermal growth factor
      receptor is mediated by metalloprotease-dependent formation of heparin-binding
      epidermal growth factor.
AB  - Numerous external stimuli, including G protein-coupled receptor agonists,
      cytokines, growth factors, and steroids activate mitogen-activated protein
      kinases (MAPKs) through phosphorylation of the epidermal growth factor receptor
      (EGF-R). In immortalized hypothalamic neurons (GT1-7 cells), agonist binding to
      the gonadotropin-releasing hormone receptor (GnRH-R) causes phosphorylation of
      MAPKs that is mediated by protein kinase C (PKC)-dependent transactivation of the
      EGF-R. An analysis of the mechanisms involved in this process showed that GnRH
      stimulation of GT1-7 cells causes release/shedding of the soluble ligand, heparin
      binding epidermal growth factor (HB-EGF), as a consequence of metalloprotease
      activation. GnRH-induced phosphorylation of the EGF-R and, subsequently, of Shc,
      ERK1/2, and its dependent protein, p90RSK-1 (p90 ribosomal S6 kinase 1 or RSK-1),
      was abolished by metalloprotease inhibition. Similarly, blockade of the effect of
      HB-EGF with the selective inhibitor CRM197 or a neutralizing antibody attenuated
      signals generated by GnRH and phorbol 12-myristate 13-acetate, but not those
      stimulated by EGF. In contrast, phosphorylation of the EGF-R, Shc, and ERK1/2 by
      EGF and HB-EGF was independent of PKC and metalloprotease activity. The signaling
      characteristics of HB-EGF closely resembled those of GnRH and EGF in terms of the
      phosphorylation of EGF-R, Shc, ERK1/2, and RSK-1 as well as the nuclear
      translocation of RSK-1. However, neither the selective Src kinase inhibitor PP2
      nor the overexpression of negative regulatory Src kinase and dominant negative
      Pyk2 had any effect on HB-EGF-induced responses. In contrast to GT1-7 cells,
      human embryonic kidney 293 cells expressing the GnRH-R did not exhibit
      metalloprotease induction and EGF-R transactivation during GnRH stimulation.
      These data indicate that the GnRH-induced transactivation of the EGF-R and the
      subsequent ERK1/2 phosphorylation result from ectodomain shedding of HBEGF
      through PKC-dependent activation of metalloprotease(s) in neuronal GT1-7 cells.

PMID- 14573594
TI  - Probing the functional importance of the hexameric ring structure of RNase PH.
AB  - RNase PH is a phosphate-dependent exoribonuclease that catalyzes the removal of
      nucleotides at the 3' end of the tRNA precursor, leading to the release of
      nucleoside diphosphate, and generates the CCA end during the maturation process.
      The 1.9-A crystal structures of the apo and the phosphate-bound forms of RNase PH
      from Pseudomonas aeruginosa reveal a monomeric RNase PH with an alpha/beta-fold
      tightly associated into a hexameric ring structure in the form of a trimer of
      dimers. A five ion pair network, Glu-63-Arg-74-Asp-116-Arg-77-Asp-118 and an ion
      pair Glu-26-Arg-69 that are positioned symmetrically in the trimerization
      interface play critical roles in the formation of a hexameric ring. Single or
      double mutations of Arg-69, Arg-74, or Arg-77 in these ion pairs leads to the
      dissociation of the RNase PH hexamer into dimers without perturbing the overall
      monomeric structure. The dissociated RNase PH dimer completely lost its binding
      affinity and catalytic activity against a precursor tRNA. Our structural and
      mutational analyses of RNase PH demonstrate that the hexameric ring formation is
      a critical feature for the function of members of the RNase PH family.

PMID- 14573595
TI  - Metal binding Asp-120 in metallo-beta-lactamase L1 from Stenotrophomonas
      maltophilia plays a crucial role in catalysis.
AB  - Metallo-beta-lactamase L1 from Stenotrophomonas maltophilia is a dinuclear Zn(II)
      enzyme that contains a metal-binding aspartic acid in a position to potentially
      play an important role in catalysis. The presence of this metal-binding aspartic
      acid appears to be common to most dinuclear, metal-containing, hydrolytic
      enzymes; particularly those with a beta-lactamase fold. In an effort to probe the
      catalytic and metal-binding role of Asp-120 in L1, three site-directed mutants
      (D120C, D120N, and D120S) were prepared and characterized using metal analyses,
      circular dichroism spectroscopy, and presteady-state and steady-state kinetics.
      The D120C, D120N, and D120S mutants were shown to bind 1.6 +/- 0.2, 1.8 +/- 0.2,
      and 1.1 +/- 0.2 mol of Zn(II) per monomer, respectively. The mutants exhibited 10
      to 1000-fold drops in kcat values as compared with wild-type L1, and a general
      trend of activity, wild-type > D120N > D120C and D120S, was observed for all
      substrates tested. Solvent isotope and pH dependence studies indicate one or more
      protons in flight, with pKa values outside the range of pH 5-10 (except D120N),
      during a rate-limiting step for all the enzymes. These data demonstrate that Asp
      120 is crucial for L1 to bind its full complement of Zn(II) and subsequently for
      proper substrate binding to the enzyme. This work also confirms that Asp-120
      plays a significant role in catalysis, presumably via hydrogen bonding with
      water, assisting in formation of the bridging hydroxide/water, and a rate
      limiting proton transfer in the hydrolysis reaction.

PMID- 14573596
TI  - Crystal structure of human pirin: an iron-binding nuclear protein and
      transcription cofactor.
AB  - Pirin is a newly identified nuclear protein that interacts with the oncoprotein B
      cell lymphoma 3-encoded (Bcl-3) and nuclear factor I (NFI). The crystal structure
      of human Pirin at 2.1-A resolution shows it to be a member of the functionally
      diverse cupin superfamily. The structure comprises two beta-barrel domains, with
      an Fe(II) cofactor bound within the cavity of the N-terminal domain. These
      findings suggest an enzymatic role for Pirin, most likely in biological redox
      reactions involving oxygen, and provide compelling evidence that Pirin requires
      the participation of the metal ion for its interaction with Bcl-3 to co-regulate
      the NF-kappaB transcription pathway and the interaction with NFI in DNA
      replication. Substitution of iron by heavy metals thus provides a novel pathway
      for these metals to directly influence gene transcription. The structure suggests
      an interesting new role of iron in biology and that Pirin may be involved in
      novel mechanisms of gene regulation.

PMID- 14573597
TI  - Crystal structures of Geobacillus stearothermophilus alpha-glucuronidase
      complexed with its substrate and products: mechanistic implications.
AB  - Alpha-glucuronidases cleave the alpha-1,2-glycosidic bond between 4-O-methyl-d
      glucuronic acid and short xylooligomers as part of the hemicellulose degradation
      system. To date, all of the alpha-glucuronidases are classified as family 67
      glycosidases, which catalyze the hydrolysis via the investing mechanism. Here we
      describe several high resolution crystal structures of the alpha-glucuronidase
      (AguA) from Geobacillus stearothermophilus, in complex with its substrate and
      products. In the complex of AguA with the intact substrate, the 4-O-methyl-d
      glucuronic acid sugar ring is distorted into a half-chair conformation, which is
      closer to the planar conformation required for the oxocarbenium ion-like
      transition state structure. In the active site, a water molecule is coordinated
      between two carboxylic acids, in an appropriate position to act as a nucleophile.
      From the structural data it is likely that two carboxylic acids, Asp(364) and
      Glu(392), activate together the nucleophilic water molecule. The loop carrying
      the catalytic general acid Glu(285) cannot be resolved in some of the structures
      but could be visualized in its "open" and "closed" (catalytic) conformations in
      other structures. The protonated state of Glu(285) is presumably stabilized by
      its proximity to the negative charge of the substrate, representing a new
      variation of substrate-assisted catalysis mechanism.

PMID- 14573598
TI  - Escherichia coli DNA polymerase V subunit exchange: a post-SOS mechanism to
      curtail error-prone DNA synthesis.
AB  - DNA polymerase V consisting of a heterotrimer composed of one molecule of UmuC
      and two molecules of UmuD' (UmuD'2C) is responsible for SOS damage-induced
      mutagenesis in Escherichia coli. Here we show that although the UmuD'2C complex
      remains intact through multiple chromatographic steps, excess UmuD, the precursor
      to UmuD', displaces UmuD' from UmuD'2C by forming a UmuDD' heterodimer, while
      UmuC concomitantly aggregates as an insoluble precipitate. Although soluble
      UmuD'2C is readily detected when the two genes are co-transcribed and translated
      in vitro, soluble UmuD2C or UmuDD'C are not detected. The subunit exchange
      between UmuD'2C and UmuD offers a biological means to inactivate error-prone
      polymerase V following translesion synthesis, thus preventing mutations from
      occurring on undamaged DNA.

PMID- 14573599
TI  - The crystal structure of gankyrin, an oncoprotein found in complexes with cyclin
      dependent kinase 4, a 19 S proteasomal ATPase regulator, and the tumor
      suppressors Rb and p53.
AB  - Gankyrin is a 25-kDa hepatocellular carcinoma-associated protein that mediates
      protein-protein interactions in cell cycle control and protein degradation. It
      has been reported to form complexes with cyclin-dependent kinase 4,
      retinoblastoma protein, the S6b ATPase subunit of the 19 S regulator of the 26 S
      proteasome, and Mdm2, an E3 ubiquitin ligase involved in p53 degradation. It is
      the first protein described to bind both to the 26 S proteasome and to proteins
      in other complexes containing cyclin-dependent kinase(s) and p53 ubiquitylating
      activities, thus providing a mechanism for delivering cell cycle regulating
      machinery and ubiquitylated substrates to the proteasome for degradation.
      Gankyrin contains a 33-residue motif known as the ankyrin repeat that occurs five
      and a half to six times in the sequence. As a step toward understanding gankyrin
      interactions with its protein partners we have determined its three-dimensional
      crystal structure to 2.0-A resolution. It reveals that the entire 226-residue
      gankyrin polypeptide folds into seven ankyrin repeat elements. The ankyrin
      repeats, consisting of an antiparallel beta-hairpin followed by a perpendicularly
      oriented helix-loop-helix, pack side-by-side, creating an extended curved
      structure with a groove running across the long concave surface. Comparison with
      the structures of other ankyrin repeat proteins suggests that interactions with
      partner proteins are mediated by residues situated on this concave surface.

PMID- 14573600
TI  - Plant MAPK phosphatase interacts with calmodulins.
AB  - A mitogen-activated protein kinase (MAPK) phosphatase gene, designated NtMKP1,
      was isolated as a candidate gene for a calmodulin (CaM)-binding protein from
      tobacco. NtMKP1 protein has four characteristic domains conserved among plant
      MAPK phosphatases reported so far, namely a dual specificity protein phosphatase
      catalytic domain, gelsolin-like domain, putative CaM-binding domain (CaMBD), and
      serine-rich region, indicating that NtMKP1 is the ortholog of Arabidopsis MKP1.
      The bacterially expressed NtMKP1 protein physically interacted with three plant
      specific types of CaM in an overlay assay with labeled CaMs, showing high
      affinity to NtCaM1 and NtCaM3 but lower affinity to NtCaM13. The peptide for the
      putative CaMBD bound both NtCaM1 and NtCaM3 significantly but bound NtCaM13 only
      slightly. Moreover, CaM overlay assays with mutated CaMBDs revealed that Trp440
      and Leu443 in the middle of the basic amphiphilic alpha-helix motif (amino acids
      436-453) are critical for binding CaM. In comparison with the transient
      accumulation of a wound-induced MAPK, WIPK transcript, a prolonged activation of
      NtMKP1 expression was found in response to wounding and tobacco mosaic virus
      induced hypersensitive reaction. In transgenic tobacco plants overexpressing
      NtMKP1, wound-induced activation of SIPK, salicylic acid-induced MAPK, and WIPK
      was inhibited. These results suggest that plant CaMs are involved in these stress
      activated MAPK cascades via NtMKP1.

PMID- 14573601
TI  - Crystal structure of the bifunctional chorismate synthase from Saccharomyces
      cerevisiae.
AB  - Chorismate synthase (EC 4.2.3.5), the seventh enzyme in the shikimate pathway,
      catalyzes the transformation of 5-enolpyruvylshikimate 3-phosphate (EPSP) to
      chorismate, which is the last common precursor in the biosynthesis of numerous
      aromatic compounds in bacteria, fungi, and plants. The chorismate synthase
      reaction involves a 1,4-trans-elimination of phosphoric acid from EPSP and has an
      absolute requirement for reduced FMN as a cofactor. We have determined the three
      dimensional x-ray structure of the yeast chorismate synthase from
      selenomethionine-labeled crystals at 2.2-A resolution. The structure shows a
      novel betaalphabetaalpha fold consisting of an alternate tight packing of two
      alpha-helical and two beta-sheet layers, showing no resemblance to any documented
      protein structure. The molecule is arranged as a tight tetramer with D2 symmetry,
      in accordance with its quaternary structure in solution. Electron density is
      missing for 23% of the amino acids, spread over sequence regions that in the
      three-dimensional structure converge on the surface of the protein. Many totally
      conserved residues are contained within these regions, and they probably form a
      structured but mobile domain that closes over a cleft upon substrate binding and
      catalysis. This hypothesis is supported by previously published spectroscopic
      measurements implying that the enzyme undergoes considerable structural changes
      upon binding of both FMN and EPSP.

PMID- 14573602
TI  - Low force decelerates L-selectin dissociation from P-selectin glycoprotein ligand
      1 and endoglycan.
AB  - Selectin-ligand interactions mediate the tethering and rolling of circulating
      leukocytes on vascular surfaces during inflammation and immune surveillance. To
      support rolling, these interactions are thought to have rapid off-rates that
      increase slowly as wall shear stress increases. However, the increase of off-rate
      with force, an intuitive characteristic named slip bonds, is at odds with a shear
      threshold requirement for selectin-mediated cell rolling. As shear drops below
      the threshold, fewer cells roll and those that do roll less stably and with
      higher velocity. We recently demonstrated a low force regime where the off-rate
      of P-selectin interacting with P-selectin glycoprotein ligand-1 (PSGL-1)
      decreased with increasing force. This counter-intuitive characteristic, named
      catch bonds, might partially explain the shear threshold phenomenon. Because L
      selectin-mediated cell rolling exhibits a much more pronounced shear threshold,
      we used atomic force microscopy and flow chamber experiments to determine off
      rates of L-selectin interacting with their physiological ligands and with an
      antibody. Catch bonds were observed at low forces for L-selectin-PSGL-1
      interactions coinciding with the shear threshold range, whereas slip bonds were
      observed at higher forces. These catch-slip transitional bonds were also observed
      for L-selectin interacting with endoglycan, a newly identified PSGL-1-like
      ligand. By contrast, only slip bonds were observed for L-selectin-antibody
      interactions. These findings suggest that catch bonds contribute to the shear
      threshold for rolling and are a common characteristic of selectin-ligand
      interactions.

PMID- 14573603
TI  - Identifying androsterone (ADT) as a cognate substrate for human
      dehydroepiandrosterone sulfotransferase (DHEA-ST) important for steroid
      homeostasis: structure of the enzyme-ADT complex.
AB  - In steroid biosynthesis, human dehydroepiandrosterone sulfotransferase (DHEA-ST)
      in the adrenals has been reported to catalyze the transfer of the sulfonate group
      from 3'-phosphoadenosine-5'-phosphosulfate to dehydroepiandrosterone (DHEA). DHEA
      and its sulfate play roles as steroid precursors; however, the role of the enzyme
      in the catabolism of androgens is poorly understood. Androsterone sulfate is
      clinically recognized as one of the major androgen metabolites found in urine.
      Here it is demonstrated that this enzyme recognizes androsterone (ADT) as a
      cognate substrate with similar kinetics but a 2-fold specificity and stronger
      substrate inhibition than DHEA. The structure of human DHEA-ST in complex with
      ADT has been solved at 2.7 A resolution, confirming ADT recognition. Structural
      analysis has revealed the binding mode of ADT differs from that of DHEA, despite
      the similarity of the overall structure between the ADT and the DHEA binary
      complexes. Our results identify that this human enzyme is an ADT sulfotransferase
      as well as a DHEA sulfotransferase, implying an important role in steroid
      homeostasis for the adrenals and liver.

PMID- 14573604
TI  - VDAC1 is a transplasma membrane NADH-ferricyanide reductase.
AB  - Porin isoform 1 or VDAC (voltage-dependent anion-selective channel) 1 is the
      predominant protein in the outer mitochondrial membrane. We demonstrated
      previously that a plasma membrane NADH-ferricyanide reductase activity becomes up
      regulated upon mitochondrial perturbation, and therefore suggested that it
      functions as a cellular redox sensor. VDAC1 is known to be expressed in the
      plasma membrane; however, its function there remained a mystery. Here we show
      that VDAC1, when expressed in the plasma membrane, functions as a NADH
      ferricyanide reductase. VDAC1 preparations purified from both plasma membrane and
      mitochondria fractions exhibit NADH-ferricyanide reductase activity, which can be
      immunoprecipitated with poly- and monoclonal antibodies directed against VDAC(1).
      Transfecting cells with pl-VDAC1-GFP, which carries an N-terminal signal peptide,
      directs VDAC1 to the plasma membrane, as shown by confocal microscopy and FACS
      analysis, and significantly increases the plasma membrane NADH-ferricyanide
      reductase activity of the transfected cells. This novel enzymatic activity of the
      well known VDAC1 molecule may provide an explanation for its role in the plasma
      membrane. Our data suggest that a major function of VDAC1 in the plasma membrane
      is that of a NADH(-ferricyanide) reductase that may be involved in the
      maintenance of cellular redox homeostasis.

PMID- 14573605
TI  - Interactions between small heat shock protein subunits and substrate in small
      heat shock protein-substrate complexes.
AB  - Small heat shock proteins (sHSPs) are dynamic oligomeric proteins that bind
      unfolding proteins and protect them from irreversible aggregation. This binding
      results in the formation of sHSP-substrate complexes from which substrate can
      later be refolded. Interactions between sHSP and substrate in sHSP-substrate
      complexes and the mechanism by which substrate is transferred to ATP-dependent
      chaperones for refolding are poorly defined. We have established C-terminal
      affinity-tagged sHSPs from a eukaryote (pea HSP18.1) and a prokaryote
      (Synechocystis HSP16.6) as tools to investigate these issues. We demonstrate that
      sHSP subunit exchange for HSP18.1 and HSP16.6 is temperature-dependent and rapid
      at the optimal growth temperature for the organism of origin. Increasing the
      ratio of sHSP to substrate during substrate denaturation decreased sHSP-substrate
      complex size, and accordingly, addition of substrate to pre-formed sHSP-substrate
      complexes increased complex size. However, the size of pre-formed sHSP-substrate
      complexes could not be reduced by addition of more sHSP, and substrate could not
      be observed to transfer to added sHSP, although added sHSP subunits continued to
      exchange with subunits in sHSP-substrate complexes. Thus, although some number of
      sHSP subunits within complexes remain dynamic and may be important for complex
      structure/solubility, association of substrate with the sHSP does not appear to
      be similarly dynamic. These observations are consistent with a model in which ATP
      dependent chaperones associate directly with sHSP-bound substrate to initiate
      refolding.

PMID- 14573607
TI  - Catalytic properties of the archaeal S-adenosylmethionine decarboxylase from
      Methanococcus jannaschii.
AB  - S-Adenosylmethionine decarboxylase (AdoMetDC) is a pyruvoyl cofactor-dependent
      enzyme that participates in polyamine biosynthesis. AdoMetDC from the Archaea
      Methanococcus jannaschii is a prototype for a recently discovered class that is
      not homologous to the eucaryotic enzymes or to a distinct group of microbial
      enzymes. M. jannaschii AdoMetDC has a Km of 95 microm and the turnover number
      (kcat) of 0.0075 s(-1) at pH 7.5 and 22 degrees C. The turnover number increased
      approximately 38-fold at a more physiological temperature of 80 degrees C.
      AdoMetDC was inactivated by treatment with the imine reductant NaCNBH3 only in
      the presence of substrate. Mass spectrometry of the inactivated protein showed
      modification solely of the pyruvoyl-containing subunit, with a mass increase
      corresponding to reduction of a Schiff base adduct with decarboxylated AdoMet.
      The presteady state time course of the AdoMetDC reaction revealed a burst of
      product formation; thus, a step after CO2 formation is rate-limiting in turnover.
      Comparable D2O kinetic isotope effects of were seen on the first turnover (1.9)
      and on kcat/Km (1.6); there was not a significant D2O isotope effect on kcat,
      suggesting that product release is rate-limiting in turnover. The pH dependence
      of the steady state rate showed participation of acid and basic groups with pK
      values of 5.3 and 8.2 for kcat and 6.5 and 8.3 for kcat/Km, respectively. The
      competitive inhibitor methylglyoxal bis(guanylhydrazone) binds at a single site
      per (alphabeta) heterodimer. UV spectroscopic studies show that methylglyoxal
      bis(guanylhydrazone) binds as the dication with a 23 microm dissociation
      constant. Studies with substrate analogs show a high specificity for AdoMet.

PMID- 14573606
TI  - Mechanism of p21-activated kinase 6-mediated inhibition of androgen receptor
      signaling.
AB  - PAK6 was first identified as an androgen receptor (AR)-interacting protein able
      to inhibit AR-mediated transcriptional responses. PAK6 is a serine/threonine
      kinase belonging to the p21-activated kinase (PAK) family implicated in actin
      reorganization and cell motility, gene transcription, apoptosis, and cell
      transformation. We investigated the biochemical basis for inhibition of AR
      signaling by PAK6. We compared the kinase activity of PAK6 with two other well
      characterized members of the PAK family, PAK1 and PAK4. Like PAK4, PAK6 possesses
      a constitutive basal kinase activity that, unlike PAK1, is not modulated by the
      binding of active Rac or Cdc42 GTPases. In order to test the involvement of PAK6
      kinase activity in suppression of AR-mediated transcription, we generated kinase
      dead (K436A) and kinase-active (S531N) mutants of PAK6. We show that PAK6 kinase
      activity is required for effective PAK6-induced repression of AR signaling.
      Suppression does not depend upon GTPase binding to PAK6 and is not mimicked by
      the closely related PAK1 and PAK4 isoforms. Kinase-dependent inhibition by PAK6
      extended to the enhanced AR-mediated transcription seen in the presence of
      coactivating molecules and to the action of AR coinhibitors. Active PAK6
      inhibited nuclear translocation of the stimulated AR, suggesting a possible
      mechanism for inhibition of AR responsiveness. Finally, we observe that
      autophosphorylated, active PAK6 protein is differently expressed among prostate
      cancer cell lines. Modulation of PAK6 activity may be responsible for regulation
      of AR signaling in various forms of prostate cancer.

PMID- 14573608
TI  - Rapamycin-resistant proliferation of CD8+ T cells correlates with p27kip1 down
      regulation and bcl-xL induction, and is prevented by an inhibitor of
      phosphoinositide 3-kinase activity.
AB  - Rapamycin inhibits the proliferation of many mammalian cell types, including
      lymphocytes, making the compound useful as an immunosuppressant. Rapamycin has
      also been a useful tool for studying signaling mechanisms regulating cellular
      proliferation. However, the effects of rapamycin remain poorly understood, and
      the precise mechanisms of clinical action remain elusive. Previously, we found
      that, depending on the strength of the signal delivered to the T cell via both
      the T cell receptor and the costimulatory molecule CD28, CD8+ T cells are capable
      of rapamycin-resistant proliferation. Here, we have further elucidated the
      mechanism of rapamycin-resistant proliferation of human CD8+ T cells. Under
      conditions where rapamycin inhibited proliferation, p27kip1 down-regulation was
      prevented, whereas under conditions resulting in rapamycin-resistant
      proliferation, p27kip1 was down-regulated. Further, T cell receptor/CD28
      dependent induction of bcl-xL expression was not inhibited by rapamycin, which
      correlated with both rapamycin-resistant proliferation and increased cell
      survival. Moreover, an inhibitor of phosphoinositide 3-kinase activity was able
      to eliminate rapamycin-resistant proliferation of freshly isolated CD8+ human
      cells, strongly suggesting that phosphoinositide 3-kinase activity was required
      for the rapamycin-resistant proliferation of CD8+ T cells. The selective
      immunosuppressive effect of rapamycin in human CD8+ T cell populations could be
      predictive of a selective effect allowing cytotoxic responses during microbial
      infections where there are strong strengths of signals associated with high
      affinity T cell receptors and strong costimulatory second signals. In contrast,
      the weaker autoimmune and perhaps allogeneic responses can be selectively
      inhibited by the actions of rapamycin.

PMID- 14573609
TI  - Secretion of heparanase protein is regulated by glycosylation in human tumor cell
      lines.
AB  - The endo-beta-d-glucuronidase, heparanase, is capable of specifically degrading
      heparan sulfate, and this activity is associated with the metastatic potential of
      tumor cells. The predicted amino acid sequence of heparanase includes six
      putative N-glycosylation sites; however, the precise biochemical role of
      glycosylated heparanase remains unknown. In this study, we examined the link
      between glycosylation and the function of heparanase in human tumor cell lines.
      Heparanase protein was glycosylated at six Asn residues in human tumor cell
      lines. Treatment with a glycosylation inhibitor demonstrated that glycosylation
      was not required for the activity of heparanase. However, glycosylation affected
      the kinetics of endoplasmic reticulum-to-Golgi transport and of secretion of the
      enzyme.

PMID- 14573610
TI  - Hydroxyurea arrests DNA replication by a mechanism that preserves basal dNTP
      pools.
AB  - The relationship between dNTP levels and DNA synthesis was investigated using
      alpha factor-synchronized yeast treated with the ribonucleotide reductase
      inhibitor hydroxyurea (HU). Although HU blocked DNA synthesis and prevented the
      dNTP pool expansion that normally occurs at G1/S, it did not exhaust the levels
      of any of the four dNTPs, which dropped to about 80% of G1 levels. When dbf4
      yeast that are ts for replication initiation were allowed to preaccumulate dNTPs
      at 37 degrees C before being released to 25 degrees C in the presence of HU, they
      synthesized 0.3 genome equivalents of DNA and then arrested as dNTPs approached
      sub-G1 levels. Accumulation of dNTPs at G1/S was not a prerequisite for
      replication initiation, since dbf4 cells incubated in HU at 25 degrees C were
      able to replicate when subsequently switched to 37 degrees C in the absence of
      HU. The replication arrest mechanism was not dependent on the Mec1/Rad53 pathway,
      since checkpoint-deficient rad53 cells also failed to exhaust basal dNTPs when
      incubated in HU. The persistence of basal dNTP levels in HU-arrested cells and
      partial bypass of the arrest in cells that had preaccumulated dNTPs suggest that
      cells have a mechanism for arresting DNA chain elongation when dNTP levels are
      not maintained above a critical threshold.

PMID- 14573611
TI  - Ultraviolet-C overexposure induces programmed cell death in Arabidopsis, which is
      mediated by caspase-like activities and which can be suppressed by caspase
      inhibitors, p35 and Defender against Apoptotic Death.
AB  - Plants, animals, and several branches of unicellular eukaryotes use programmed
      cell death (PCD) for defense or developmental mechanisms. This argues for a
      common ancestral apoptotic system in eukaryotes. However, at the molecular level,
      very few regulatory proteins or protein domains have been identified as conserved
      across all eukaryotic PCD forms. A very important goal is to determine which
      molecular components may be used in the execution of PCD in plants, which have
      been conserved during evolution, and which are plant-specific. Using Arabidopsis
      thaliana, we have shown that UV radiation can induce apoptosis-like changes at
      the cellular level and that a UV experimental system is relevant to the study of
      PCD in plants. We report here that UV induction of PCD required light and that a
      protease cleaving the caspase substrate Asp-Glu-Val-Asp (DEVDase activity) was
      induced within 30 min and peaked at 1 h. This DEVDase appears to be related to
      animal caspases at the biochemical level, being insensitive to broad-range
      cysteine protease inhibitors. In addition, caspase-1 and caspase-3 inhibitors and
      the pan-caspase inhibitor p35 were able to suppress DNA fragmentation and cell
      death. These results suggest that a YVADase activity and an inducible DEVDase
      activity possibly mediate DNA fragmentation during plant PCD induced by UV
      overexposure. We also report that At-DAD1 and At-DAD2, the two A. thaliana
      homologs of Defender against Apoptotic Death-1, could suppress the onset of DNA
      fragmentation in A. thaliana, supporting an involvement of the endoplasmic
      reticulum in this form of the plant PCD pathway.

PMID- 14573612
TI  - Identification of an expanded binding surface on the FADD death domain
      responsible for interaction with CD95/Fas.
AB  - The initiation of programmed cell death at CD95 (Fas, Apo-1) is achieved by
      forming a death-inducing signaling complex (DISC) at the cytoplasmic membrane
      surface. Assembly of the DISC has been proposed to occur via homotypic
      interactions between the death domain (DD) of FADD and the cytoplasmic domain of
      CD95. Previous analysis of the FADD/CD95 interaction led to the identification of
      a putative CD95 binding surface within FADD DD formed by alpha helices 2 and 3.
      More detailed analysis of the CD95/FADD DD interaction now demonstrates that a
      bimodal surface exists in the FADD DD for interaction with CD95. An expansive
      surface on one side of the domain is composed of elements in alpha helices 1, 2,
      3, 5, and 6. This major surface is common to many proteins harboring this motif,
      whether or not they are associated with programmed cell death. A secondary
      surface resides on the opposite face of the domain and involves residues in
      helices 3 and 4. The major surface is topologically similar to the protein
      interaction surface identified in Drosophila Tube DD and the death effector
      domain of hamster PEA-15, two physiologically unrelated proteins which interact
      with structurally unrelated binding partners. These results demonstrate the
      presence of a structurally conserved surface within the DD which can mediate
      protein recognition with homo- and heterotypic binding partners, whereas a second
      surface may be responsible for stabilizing the higher order complex in the DISC.

PMID- 14573613
TI  - Artificial modules for enhancing rate constants of a Group I intron ribozyme
      without a P4-P6 core element.
AB  - In this paper we report newly selected artificial modules that enhance the kcat
      values comparable with or higher than those of the wild-type ribozyme with broad
      substrate specificity. The elements required for the catalysis of Group I intron
      ribozymes are concentrated in the P3-P7 domain of their core region, which
      consists of two conserved helical domains, P4-P6 and P3-P7. Previously, we
      reported the in vitro selection of artificial modules residing at the peripheral
      region of a mutant Group I ribozyme lacking P4-P6. We found that derivatives of
      the ribozyme containing the modules performed the reversal of the first step of
      the self-splicing reaction efficiently by using their affinity to the substrate
      RNA, although their kcat values and substrate specificity were uninfluenced and
      limited, respectively. The results show that it is possible to add a variety of
      new domains at the peripheral region that play a role comparable with that of the
      conserved P4-P6 domain.

PMID- 14573614
TI  - The carboxyl terminus controls ligand-dependent activation of VEGFR-2 and its
      signaling.
AB  - Vascular endothelial growth factor receptor-2 (VEGFR-2/FLK-1) is a receptor
      tyrosine kinase whose activation stimulates angiogenesis. We recently generated a
      chimeric VEGFR-2 in which the extracellular domain of VEGFR-2 was replaced with
      the extracellular domain of human colony stimulating factor-1 receptor and
      expressed in endothelial cells. To study the contribution of the carboxyl
      terminus to activation of VEGFR-2, we created a panel of truncated receptors in
      which the carboxyl terminus of VEGFR-2 was progressively deleted. Removal of the
      entire carboxyl terminus eliminated activation of VEGFR-2, its ability to
      activate signaling proteins, and its ability to stimulate cell proliferation. The
      carboxyl terminus-deleted VEGFR-2 exhibited impaired ligand-dependent down
      regulation and inhibited the activation of wild-type receptor in a dominant
      negative fashion. Furthermore, introducing the carboxyl terminus of another
      receptor, i.e., VEGFR-1, restored the ligand-dependent activation of the carboxyl
      terminus-deleted VEGFR-2 and its ability to stimulate cell proliferation. Our
      findings suggest that the carboxyl terminus of VEGFR-2 plays a critical role in
      VEGFR-2 activation, its ability to activate signaling proteins, and its ability
      to induce biological responses. The presence of at least 57 amino acids at the
      carboxyl terminus of VEGFR-2 are required for VEGFR-2 activation. Thus, we
      propose that the carboxyl terminus is required for activation of VEGFR-2, and
      absence of the carboxyl terminus renders VEGFR-2 inactive.

PMID- 14573615
TI  - Structure of the sterile alpha motif (SAM) domain of the Saccharomyces cerevisiae
      mitogen-activated protein kinase pathway-modulating protein STE50 and analysis of
      its interaction with the STE11 SAM.
AB  - The sterile alpha motif (SAM) is a 65-70-amino acid domain found in over 300
      proteins that are involved in either signal transduction or transcriptional
      activation and repression. SAM domains have been shown to mediate both
      homodimerization and heterodimerization and in some cases oligomerization. Here,
      we present the solution structure of the SAM domain of the Saccharomyces
      cerevisiae protein, Ste50p. Ste50p functions as a modulator of the mitogen
      activated protein kinase (MAPK) cascades in S. cerevisiae, which control mating,
      pseudohyphal growth, and osmo-tolerance. This is the first example of the
      structure of a SAM domain from a MAPK module protein. We have studied the
      associative behavior of Ste50p SAM in solution and shown that it is monomeric. We
      have examined the SAM domain from Ste11p, the MAPK kinase kinase that associates
      with Ste50p in vivo, and shown that it forms dimers with a self-association K(d)
      of approximately 0.5 mm. We have also analyzed the interaction of Ste50p SAM with
      Ste11p SAM and the effects of mutations at Val-37, Asp-38, Pro-71, Leu-73, Leu
      75, and Met-99 of STE50 on the heterodimerization properties of Ste50p SAM. We
      have found that L73A and L75A abrogate the Ste50p interaction with Ste11p, and we
      compare these data with the known interaction sites defined for other SAM domain
      interactions.

PMID- 14573617
TI  - Regulation of platelet-derived growth factor-A chain by Kruppel-like factor 5:
      new pathway of cooperative activation with nuclear factor-kappaB.
AB  - The transcription factor Kruppel-like factor 5 (KLF5) and its genetically
      downstream target gene platelet-derived growth factor-A (PDGF-A) chain are key
      factors in regulation of cardiovascular remodeling in response to stress. We show
      that KLF5 mediates a novel distinct delayed persistent induction of PDGF-A chain
      in response to the model agonist, phorbol ester, through a cis-element previously
      shown to mediate phorbol ester induction on to PDGF-A chain through the early
      growth response factor (Egr-1). Interestingly, the nuclear factor-kappaB (NF
      kappaB) p50 subunit further cooperatively activates PDGF-A chain through protein
      protein interaction with KLF5 but not Egr-1. RNA interference analysis confirmed
      that KLF5 and p50 are important for induction of PDGF-A chain. Collectively, we
      identify a novel regulatory pathway in which PDGF-A chain gene expression, under
      the control of KLF5, is cooperatively activated by the NF-kappaB p50 subunit and
      a pathophysiological stimulus.

PMID- 14573616
TI  - Knockout of the alpha2 but not alpha1 5'-AMP-activated protein kinase isoform
      abolishes 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranosidebut not
      contraction-induced glucose uptake in skeletal muscle.
AB  - We investigated the importance of the two catalytic alpha-isoforms of the 5'-AMP
      activated protein kinase (AMPK) in 5-aminoimidazole-4-carboxamide-1-beta-4
      ribofuranoside (AICAR) and contraction-induced glucose uptake in skeletal muscle.
      Incubated soleus and EDL muscle from whole-body alpha2- or alpha1-AMPK knockout
      (KO) and wild type (WT) mice were incubated with 2.0 mm AICAR or electrically
      stimulated to contraction. Both AICAR and contraction increased 2DG uptake in WT
      muscles. KO of alpha2, but not alpha1, abolished AICAR-induced glucose uptake,
      whereas neither KO affected contraction-induced glucose uptake. AICAR and
      contraction increased alpha2- and alpha1-AMPK activity in wild type (WT) muscles.
      During AICAR stimulation, the remaining AMPK activity in KO muscles increased to
      the same level as in WT. During contraction, the remaining AMPK activity in
      alpha2-KO muscles was elevated by 100% probably explained by a 2-3-fold increase
      in alpha1-protein. In alpha1-KO muscles, alpha2-AMPK activity increased to
      similar levels as in WT. Both interventions increased total AMPK activity, as
      expressed by AMPK-P and ACCbeta-P, in WT muscles. During AICAR stimulation, this
      was dramatically reduced in alpha2-KO but not in alpha1-KO, whereas during
      contraction, both measurements were essentially similar to WT in both KO-muscles.
      The results show that alpha2-AMPK is the main donor of basal and AICAR-stimulated
      AMPK activity and is responsible for AICAR-induced glucose uptake. In contrast,
      during contraction, the two alpha-isoforms seem to substitute for each other in
      terms of activity, which may explain the normal glucose uptake despite the lack
      of either alpha2- or alpha1-AMPK. Alternatively, neither alpha-isoform of AMPK is
      involved in contraction-induced muscle glucose uptake.

PMID- 14573618
TI  - Insertion of an N7-methylguanine mRNA cap between two coplanar aromatic residues
      of a cap-binding protein is fast and selective for a positively charged cap.
AB  - The N7-methylated guanosine (m7G) cap structure, which is found at the 5' ends of
      mature eukaryotic mRNAs, is critical to a myriad of biological processes. The
      twenty structures of complexes of cap nucleosides and nucleotides and methylated
      bases with the vaccinia virus VP39, a cap-specific RNA 2'-O-methyltransferase,
      which we have determined previously, have revealed the atomic basis of cap
      binding. The precise insertion and tight fitting of the m7Gua moiety of the cap
      between two parallel aromatic residues that are spaced only 6.8 A apart governs
      the high specificity of binding. Here we report the investigation of the reaction
      mechanism of VP39 with three capped ligands (m7G, m7GpppG, and m7GpppGA3) by
      fluorescence stopped-flow technique. Cap binding is a simple one-step mechanism
      with very fast association rate constant (approximately 10(7) M-1 s-1). Moreover,
      the pH dependence on the association rate constant of m7G binding indicates that
      only the positively charged keto tautomer of the cap is recognized and bound. The
      association and dissociation rate constants and affinity constants of the three
      ligands do not vary greatly, demonstrating that binding is achieved almost
      entirely by the interactions of m7Gua with two aromatic residues in a cation-pi
      sandwich.

PMID- 14573619
TI  - A cryptic targeting signal induces isoform-specific localization of p46Shc to
      mitochondria.
AB  - The human Src homology and collagen (Shc) gene encodes three protein isoforms of
      46, 52, and 66 kDa that belong to a family of molecular adapters involved in
      several signal transduction pathways. Recently, the 66-kDa isoform has been shown
      to play a central role in controlling reactive oxygen species metabolism and life
      span in mammals. Despite the large amount of information available on the biology
      and biochemistry of Shc proteins, very little is known regarding the regulation
      of their subcellular localization. Here we demonstrate the specific and selective
      localization of p46Shc to the mitochondrial matrix. Through deletion mapping
      experiments, we show that targeting of p46Shc to mitochondria is mediated by its
      first 32 amino acids, which behave as a bona fide mitochondrial targeting
      sequence. We further demonstrate that the N-terminal location of the signal
      peptide is critical for its function. This accounts for the observation that
      p52Shc and p66Shc, containing the same sequence but more internally located,
      display a remarkably different subcellular localization. These findings indicate
      that p46Shc may exert a non-redundant biological function in signal transduction
      pathways involving mitochondria.

PMID- 14573620
TI  - Strain-specific kinetics of prion protein formation in vitro and in vivo.
AB  - The molecular basis of prion strain diversity is proposed to be encoded by
      distinct conformations of the abnormal scrapie isoform of the prion protein
      (PrP(Sc)). PrP(Sc) formation for the hyper (HY) and drowsy (DY) strains of the
      transmissible mink encephalopathy (TME) agent was investigated using the cell
      free PrP conversion reaction to determine the role of distinct PrP(Sc)
      conformations in the rate of in vitro conversion of cellular PrP into protease
      resistant PrP. PrP conversion increased at an exponential rate for both TME
      strains until peak levels were reached at 72-96 h of reaction time. The amount
      and rate of PrP conversion for HY TME was greater than those for DY TME between
      48 h and the peak level of PrP conversion. Between 96 and 120 h, there was a
      negative rate of PrP conversion; and between 120 and 168 h, the net rate of HY
      and DY PrP conversion approached zero. These findings suggest that PrP conversion
      can occur in three distinct stages: an elongation phase, a depolymerization
      phase, and a steady-state phase. Strain-specific properties between the TME
      strains were identified only during the elongation phase. The steady-state phase
      could be disrupted by the addition of PrP(Sc) to, or by sonication of, the cell
      free PrP conversion reaction. These treatments resulted in an increase in the
      amount of PrP conversion that was equal to or greater than that found during the
      peak level of PrP conversion for both TME strains, indicating that the steady
      state phase was in dynamic equilibrium. In a related study, the rate of
      accumulation of HY and DY PrP(Sc) in hamster brain exhibited a strain-specific
      pattern that had similarities to the strain-specific PrP conversion reaction
      during the elongation phase. These results suggest that strain-specific
      conformations of PrP(Sc) have the ability to influence the rate of additional
      PrP(Sc) formation from cellular PrP both in vitro and in vivo.

PMID- 14573621
TI  - Helicobacter pylori heat shock protein 60 mediates interleukin-6 production by
      macrophages via a toll-like receptor (TLR)-2-, TLR-4-, and myeloid
      differentiation factor 88-independent mechanism.
AB  - Helicobacter pylori has been reported to induce interleukin-6 (IL-6) production
      in monocytes/macrophages and in chronically inflamed gastric tissues. The
      mechanism by which H. pylori induces IL-6 production in macrophages, however, has
      not been investigated. To identify the H. pylori factor responsible for this
      activity, we fractionated soluble proteins from H. pylori strain 26695 by ion
      exchange and size exclusion chromatography and screened the fractions for IL-6
      inducing activity on RAW 264.7 macrophages. A single protein was purified and
      identified by mass spectrometry as H. pylori heat shock protein 60 (HSP60).
      Consistent with the observed IL-6-inducing activity of H. pylori HSP60, soluble
      protein extracts of H. pylori 26695 and SS1 strains that were depleted of this
      protein by affinity chromatography had dramatically reduced IL-6-inducing
      activities. The immunopurified HSP60 stimulated IL-6 production in macrophages.
      When stimulated with H. pylori HSP60 or intact bacteria, peritoneal macrophages
      from mice deficient in Toll-like receptor (TLR)-2, TLR-4, TLR-2/TLR-4, and
      myeloid differentiation factor 88 produced the same amount of IL-6 than
      macrophages from wild-type mice, demonstrating the independence of H. pylori
      HSP60 responses from these signaling molecules. H. pylori HSP60-induced IL-6 mRNA
      expression, and NF-kappaB activation in RAW 264.7 cells was abrogated in the
      presence of MG-132, a proteasome inhibitor. In contrast, inhibitors of protein
      kinase A or C, mitogen-activated protein kinase kinase, and phosphoinositide 3
      kinase had no effect on IL-6 mRNA levels. This study demonstrates the induction
      of innate immune responses by H. pylori HSP60, thereby implicating this highly
      conserved protein in the pathophysiology of chronic gastritis.

PMID- 14573622
TI  - CLMP, a novel member of the CTX family and a new component of epithelial tight
      junctions.
AB  - The CTX family is a growing group of type I transmembrane proteins within the
      immunoglobulin superfamily (IgSF). They localize to junctional complexes between
      endothelial and epithelial cells and seem to participate in cell-cell adhesion
      and transmigration of leukocytes. Here, we report the identification of a new
      member of the CTX family. This protein, which was designated CLMP (coxsackie- and
      adenovirus receptor-like membrane protein), is composed of 373 amino acids
      including an extracellular part containing a V- and a C2-type domain, a
      transmembrane region and a cytoplasmic tail. CLMP mRNA was detected in a variety
      of both human and mouse tissues and cell lines. The protein migrated with an Mr
      of around 48 on SDS-PAGE and was predominantly expressed in epithelial cells
      within different tissues. In cultured epithelial cells, CLMP was detected in
      areas of cell-cell contacts. When exogenously expressed in polarized MDCK cells,
      CLMP was restricted to the subapical area of the lateral cell surface, where it
      co-localized with the tight junction markers ZO-1 and occludin. Also endogenous
      CLMP showed association with tight junctions, as analyzed in polarized human CACO
      2 cells. This suggested a role for CLMP in cell-cell adhesion and indeed,
      overexpressed CLMP induced aggregation of non-polarized CHO cells. Furthermore,
      CLMP-expressing MDCK cells showed significantly increased transepithelial
      resistance, indicating a role for CLMP in junctional barrier function. Thus, we
      conclude that CLMP is a novel cell-cell adhesion molecule and a new component of
      epithelial tight junctions. We also suggest, based on phylogenetic studies, that
      CLMP, CAR, ESAM, and BT-IgSF form a new group of proteins within the CTX family.

PMID- 14573623
TI  - Activation of syndecan-1 ectodomain shedding by Staphylococcus aureus alpha-toxin
      and beta-toxin.
AB  - Exploitation of host components by microbes to promote their survival in the
      hostile host environment has been a recurring theme in recent years. Available
      data indicate that bacterial pathogens activate ectodomain shedding of host cell
      surface molecules to enhance their virulence. We reported previously that several
      major bacterial pathogens activate ectodomain shedding of syndecan-1, the major
      heparan sulfate proteoglycan of epithelial cells. Here we define the molecular
      basis of how Staphylococcus aureus activates syndecan-1 shedding. We screened
      mutant S. aureus strains devoid of various toxin and protease genes and found
      that only strains lacking both alpha-toxin and beta-toxin genes do not stimulate
      shedding. Mutations in the agr global regulatory locus, which positively
      regulates expression of alpha- and beta-toxins and other exoproteins, also
      abrogated the capacity to stimulate syndecan-1 shedding. Furthermore, purified S.
      aureus alpha- and beta-toxins, but not enterotoxin A and toxic shock syndrome
      toxin-1, rapidly potentiated shedding in a concentration-dependent manner. These
      results establish that S. aureus activates syndecan-1 ectodomain shedding via its
      two virulence factors, alpha- and beta-toxins. Toxin-activated shedding was also
      selectively inhibited by antagonists of the host cell shedding mechanism,
      indicating that alpha- and beta-toxins shed syndecan-1 ectodomains through
      stimulation of the host cell's shedding machinery. Interestingly, beta-toxin, but
      not alpha-toxin, also enhanced ectodomain shedding of syndecan-4 and heparin
      binding epidermal growth factor. Because shedding of these ectodomains has been
      implicated in promoting bacterial pathogenesis, activation of ectodomain shedding
      by alpha-toxin and beta-toxin may be a previously unknown virulence mechanism of
      S. aureus.

PMID- 14573624
TI  - Protein kinase C-independent activation of protein kinase D is involved in BMP-2
      induced activation of stress mitogen-activated protein kinases JNK and p38 and
      osteoblastic cell differentiation.
AB  - An important role for JNK* and p38 has recently been discovered in the
      differentiating effect of bone morphogenetic protein 2 (BMP-2) on osteoblastic
      cells. In this study, we investigated the molecular mechanism by which BMP-2
      activates JNK and p38 in MC3T3-E1 osteoblastic cells. Activation of JNK and p38
      induced by BMP-2 was blocked by the protein kinase C/protein kinase D (PKC/PKD)
      inhibitor Go6976 but not by the related compound, Go6983, a selective inhibitor
      of conventional PKCs. Associated with this inhibitory effect of Go6976, BMP-2
      induced a selective and a dose-dependent Ser916 phosphorylation/activation of
      PKD, which was also blocked by Go6976. In contrast to the recently described PKC
      dependent molecular mechanism involved in activation of PKD by G protein-coupled
      receptor agonists, BMP-2 did not induce a phosphorylation of PKD on Ser744/748.
      To further document an implication of PKD in activation of JNK and p38 induced by
      BMP-2, we constructed MC3T3-E1 cells stably expressing PKD antisense
      oligonucleotide (AS-PKD). In AS-PKD clones having low PKD levels, activation of
      JNK and p38 by BMP-2, but not of Smad1/5, was markedly impaired compared with
      empty vector transfected (V-PKD) cells. Analysis of osteoblastic cell
      differentiation in AS-PKD compared with V-PKD cells showed that mRNA and protein
      expressions of alkaline phosphatase and osteocalcin induced by BMP-2 were
      markedly reduced in AS-PKD. In conclusion, results presented in this study
      indicate that BMP-2 can induce activation of PKD in osteoblastic cells by a PKC
      independent mechanism and that this kinase is involved in activation of JNK and
      p38 induced by BMP-2. Thus, this pathway, in addition to Smads, appears to be
      essential for the effect of BMP-2 on osteoblastic cell differentiation.

PMID- 14573625
TI  - Apoptosis and the balance of homeostatic and pathologic responses to protozoan
      infection.

PMID- 14573626
TI  - PPE protein (Rv3873) from DNA segment RD1 of Mycobacterium tuberculosis: strong
      recognition of both specific T-cell epitopes and epitopes conserved within the
      PPE family.
AB  - Proteins encoded by DNA segment RD1 of Mycobacterium tuberculosis have recently
      been demonstrated to play important roles in bacterial virulence, vaccine
      development, and diagnostic reagent design. Previously, we characterized two
      immunodominant T-cell antigens, the early secreted antigen target (ESAT-6) and
      the 10-kDa culture filtrate protein (CFP10), which are encoded by the esx-lhp
      operon in this region. In the present study we characterized a third putative
      open reading frame in this region, rv3873, which encodes a PPE protein. We found
      that the rv3873 gene is expressed in M. tuberculosis H37Rv and that the native
      protein, Rv3873, is predominantly associated with the mycobacterial cell or wall.
      When tested as a His-tagged recombinant protein, Rv3873 stimulated high levels of
      gamma interferon secretion in peripheral blood mononuclear cells isolated from
      tuberculosis (TB) patients, as well as from healthy tuberculin purified protein
      derivative-positive donors. In contrast to other RD1-encoded antigens, Rv3873 was
      also found to be recognized by a significant proportion of Mycobacterium bovis
      BCG-vaccinated donors. Epitope mapping performed with overlapping peptides
      revealed a broad pattern of T-cell recognition comprising both TB-specific
      epitopes and epitopes also recognized by BCG-vaccinated donors. The
      immunodominant epitope (residues 118 to 135) for both TB patients and BCG
      vaccinated individuals was found to be highly conserved among a large number of
      PPE family members.

PMID- 14573627
TI  - Ribonucleotide reduction in Mycobacterium tuberculosis: function and expression
      of genes encoding class Ib and class II ribonucleotide reductases.
AB  - Mycobacterium tuberculosis, the causative agent of tuberculosis, possesses a
      class Ib ribonucleotide reductase (RNR), encoded by the nrdE and nrdF2 genes, in
      addition to a putative class II RNR, encoded by nrdZ. In this study we probed the
      relative contributions of these RNRs to the growth and persistence of M.
      tuberculosis. We found that targeted knockout of the nrdF2 gene could be achieved
      only in the presence of a complementing allele, confirming that this gene is
      essential under normal, in vitro growth conditions. This observation also implied
      that the alternate class Ib small subunit encoded by the nrdF1 gene is unable to
      substitute for nrdF2 and that the class II RNR, NrdZ, cannot substitute for the
      class Ib enzyme, NrdEF2. Conversely, a DeltanrdZ null mutant of M. tuberculosis
      was readily obtained by allelic exchange mutagenesis. Quantification of levels of
      nrdE, nrdF2, nrdF1, and nrdZ gene expression by real-time, quantitative reverse
      transcription-PCR with molecular beacons by using mRNA from aerobic and O(2)
      limited cultures showed that nrdZ was significantly induced under microaerophilic
      conditions, in contrast to the other genes, whose expression was reduced by O(2)
      restriction. However, survival of the DeltanrdZ mutant strain was not impaired
      under hypoxic conditions in vitro. Moreover, the lungs of B6D2/F(1) mice infected
      with the DeltanrdZ mutant had bacterial loads comparable to those of lungs
      infected with the parental wild-type strain, which argues against the hypothesis
      that nrdZ plays a significant role in the virulence of M. tuberculosis in this
      mouse model.

PMID- 14573628
TI  - Salmonella enterica serovar Typhimurium expressing mutant lipid A with decreased
      endotoxicity causes maturation of murine dendritic cells.
AB  - A major Salmonella component involved in cellular activation is the
      lipopolysaccharide (LPS) molecule which can act as a dendritic cell (DC)
      stimulator. The structure of the lipid A domain of the LPS molecule dictates its
      immunostimulatory capacity with various cell types. In this study, the role of
      lipid A as an integral component of Salmonella in stimulating murine DCs was
      studied by using a Salmonella enterica serovar Typhimurium lpxM mutant with
      defective lipid A. This study revealed that a mutation in lpxM did not
      significantly affect the ability of bacteria to activate DCs. Although the lpxM
      mutant less tumor necrosis factor alpha, interleukin-1beta, and inducible nitric
      oxide synthase than the parental strain, this was only seen at lower
      multiplicities of infection (MOIs). Both strains upregulated surface molecule
      expression on DCs and augmented the T-cell-stimulating capacity of these cells in
      an MOI-independent manner. Thus, the lpxM mutation did not appear to affect the
      stimulatory capacity of the Salmonella mutant.

PMID- 14573629
TI  - One of two human lactoferrin variants exhibits increased antibacterial and
      transcriptional activation activities and is associated with localized juvenile
      periodontitis.
AB  - The iron-binding protein lactoferrin is a ubiquitous and abundant constituent of
      human exocrine secretions. Lactoferrin inhibits bacterial growth by sequestering
      essential iron and also exhibits non-iron-dependent antibacterial, antifungal,
      antiviral, antitumor, anti-inflammatory, and immunoregulatory activities. All of
      these non-iron-dependent activities are mediated by the highly charged N terminus
      of lactoferrin. In this study we characterized a Lys/Arg polymorphism at position
      29 in the N-terminal region of human lactoferrin that results from a single
      nucleotide polymorphism in exon 1 of the human lactoferrin gene. We expressed
      cDNAs encoding both lactoferrin variants in insect cells and purified the two
      proteins by ion exchange chromatography. The two lactoferrin variants exhibited
      nearly identical iron-binding and iron-releasing activities and equivalent
      bactericidal activities against a strain of the gram-negative bacterium
      Actinobacillus actinomycetemcomitans. When tested against the gram-positive
      species Streptococcus mutans and Streptococcus mitis, however, lactoferrin
      containing Lys at position 29 exhibited significantly greater bactericidal
      activity than did lactoferrin containing Arg. In addition, the Lys-containing
      lactoferrin stimulated bovine tracheal epithelial cells to synthesize much higher
      levels of tracheal antimicrobial peptide mRNA than did the Arg-containing
      variant. A genotyping assay that distinguished between the two alleles based on a
      polymorphic EarI restriction site showed that the Lys and Arg alleles had
      frequencies of 24% and 76%, respectively, among 17 healthy human subjects, and
      72% and 28%, respectively, among nine patients with localized juvenile
      periodontitis. Our findings suggest that these two lactoferrin variants are
      functionally different and that these differences may contribute to the
      pathogenesis of localized juvenile periodontitis.

PMID- 14573630
TI  - Characterization of chlamydial genital infection resulting from sexual
      transmission from male to female guinea pigs and determination of infectious
      dose.
AB  - A major problem in the study of chlamydial genital infections in animal models
      has been the use of varied doses of chlamydiae for infection in different
      laboratories. It is clearly desirable to use a dose which approximates that of
      natural sexual infection, but that dose to date has not been determined because
      of the inability of researchers to quantify chlamydiae in semen. Fortunately,
      sexual transmission of chlamydiae has been described for the guinea pig model of
      infection with the chlamydial agent of guinea pig inclusion conjunctivitis
      (GPIC). In this study, we undertook to determine the approximate infection dose
      in actual sexual transmission by comparing the kinetics of infection in female
      guinea pigs acquired via sexual contact to those of genital infections induced
      artificially with known quantities of chlamydiae. Groups of guinea pigs were
      infected intravaginally with 10(4), 10(3), 10(2), and 10(1) inclusion-forming
      units (IFU) of GPIC, and the kinetics of the infection were determined. Infection
      with 10(2) IFU produced infections with lower peak levels than those in animals
      receiving 10(4) or 10(3) IFU. Seventy percent of animals receiving 10(2) IFU
      became infected, while 100 and 79% of animals receiving 10(4) and 10(3) IFU,
      respectively, became infected. Animals receiving 10(2) IFU also had a longer
      incubation period. Of 19 animals that mated with infected males, 63.2% became
      infected, with an infection course which was not significantly different than
      that of the 10(2)-IFU-infected group. The data suggest that female guinea pigs
      received approximately 10(2) IFU by sexual transmission. Of interest was the
      observation that the guinea pigs infected by sexual transmission shed organisms
      for a significantly shorter time period than that of any group that was
      artificially infected. This result suggests that there may be factors associated
      with semen which passively transfer antimicrobial activity to the female or
      enhance the innate host response in the female. Immunization of females with an
      inactivated vaccine was also found to elicit a protective immune response against
      sexual challenge, demonstrating that the model can be used in the evaluation of
      possible vaccine candidates and/or methodologies. There is currently no other
      animal model available for any sexually transmitted disease in which the disease
      or the ability to prevent the disease may be studied in animals infected by the
      natural means.

PMID- 14573632
TI  - Differential expression of genes in uninfected and rickettsia-infected
      Dermacentor variabilis ticks as assessed by differential-display PCR.
AB  - Ticks serve as both the vector and the reservoir for members of the spotted fever
      group rickettsiae. The molecular interaction(s) that results from this close
      relationship is largely unknown. To identify genetic factors associated with the
      tick response to rickettsial infection, we utilized differential-display PCR. The
      majority of upregulation appeared in the infected tissue. We cloned and sequenced
      54 differentially expressed transcripts and compared the sequences to those in
      the GenBank database. Nine of the 54 clones were assigned putative identities and
      included a clathrin-coated vesicle ATPase, peroxisomal farnesylated protein,
      Ena/vasodilator-stimulated phosphoprotein-like protein, alpha-catenin, tubulin
      alpha-chain, copper-transporting ATPase, salivary gland protein SGS-3 precursor,
      glycine-rich protein, and Dreg-2 protein. Confirmation of the rickettsial
      influence on the differential expression in the ovaries for a number of these
      clones was demonstrated by semiquantitative reverse transcription-PCR and
      Northern blot analyses, resulting in confirmation of six out of nine and three
      out of four assessed clones, respectively. Further characterization of the clones
      identified tissue-dependent expression in the midguts and salivary glands. The
      potential roles of these molecules in the maintenance and transmission of
      rickettsiae are discussed.

PMID- 14573631
TI  - Induction of capsule growth in Cryptococcus neoformans by mammalian serum and
      CO(2).
AB  - The pathogenic fungus Cryptococcus neoformans has a polysaccharide capsule that
      is essential for virulence in vivo. Capsule size is known to increase during
      animal infection, and this phenomenon was recently associated with virulence.
      Although various conditions have been implicated in promoting capsule growth,
      including CO(2) concentration, osmolarity, and phenotypic switching, it is
      difficult to reproduce the capsule enlargement effect in the laboratory. In this
      study, we report that serum can induce capsule growth, and we describe the
      conditions that induce this effect, not only by serum but also by CO(2). Capsule
      enlargement was dependent on the medium used, and this determined whether the
      strain responded to serum or CO(2) efficiently. Serum was most effective in
      inducing capsule growth under nutrient-limited conditions. There was considerable
      variability between strains in their response to either serum or CO(2), with some
      strains requiring both stimuli. Sera from several animal sources were each highly
      efficient in inducing capsule growth. The cyclic AMP (cAMP) pathway and Ras1 were
      both necessary for serum-induced capsule growth. The lack of induction in the
      ras1 mutant was not complemented by exogenous cAMP, indicating that these
      pathways act in parallel. However, both cAMP and Ras1 were dispensable for
      inducing a partial capsule growth by CO(2), suggesting that multiple pathways
      participate in this process. The ability of serum to induce capsule growth
      suggests a mechanism for the capsular enlargement observed during animal
      infection.

PMID- 14573633
TI  - The streptococcal exotoxin streptolysin O activates mast cells to produce tumor
      necrosis factor alpha by p38 mitogen-activated protein kinase- and protein kinase
      C-dependent pathways.
AB  - Streptolysin O (SLO), a major virulence factor of pyogenic streptococci, binds to
      cholesterol in the membranes of eukaryotic cells and oligomerizes to form large
      transmembrane pores. While high toxin doses are rapidly cytocidal, low doses are
      tolerated because a limited number of lesions can be resealed. Here, we report
      that at sublethal doses, SLO activates primary murine bone marrow-derived mast
      cells to degranulate and to rapidly induce or enhance the production of several
      cytokine mRNAs, including tumor necrosis factor alpha (TNF-alpha). Mast cell
      derived TNF-alpha plays an important protective role in murine models of acute
      inflammation, and the production of this cytokine was analyzed in more detail.
      Release of biologically active TNF-alpha peaked approximately 4 h after
      stimulation with SLO. Production of TNF-alpha was blunted upon depletion of
      protein kinase C by pretreatment of the cells with phorbol-12 myristate-13
      acetate. Transient permeabilization of mast cells with SLO also led to the
      activation of the stress-activated protein kinases p38 mitogen-activated protein
      (MAP) kinase and c-jun N-terminal kinase (JNK), and inhibition of p38 MAP kinase
      markedly reduced production of TNF-alpha. In contrast, secretion of preformed
      granule constituents triggered by membrane permeabilization was not dependent on
      p38 MAP kinase or on protein kinase C. Thus, transcriptional activation of mast
      cells following transient permeabilization might contribute to host defense
      against infections via the beneficial effects of TNF-alpha. However,
      hyperstimulation of mast cells might also lead to overproduction of TNF-alpha,
      which would then promote the development of toxic streptococcal syndromes.

PMID- 14573634
TI  - Differential production of macrophage inflammatory protein 1gamma (MIP-1gamma),
      lymphotactin, and MIP-2 by CD4(+) Th subsets polarized in vitro and in vivo.
AB  - Due to differential expression of chemokine receptors, the Th1 and Th2 subsets of
      CD4(+) T cells differ in their migratory responses to chemokines. These
      differences in the migration patterns are likely to play a role in the initiation
      and regulation of Th1 and Th2 immune responses, inflammatory processes, and T
      cell-mediated pathology. In the present study we evaluated the role of activated
      Th cells as producers of chemokines. Three different sources of murine Th cells
      were used, i.e., long-term-cultured Th1 and Th2 cell clones, Th1 and Th2 cells
      differentiated from naive CD4(+) spleen and lymph node cells in vitro, and Th1
      and Th2 subsets polarized in vivo using a murine experimental Leishmania major
      infection model. Following stimulation with anti-CD3, macrophage inflammatory
      protein 1gamma (MIP-1gamma) and lymphotactin were produced selectively by Th1
      cells but not by Th2 cells. In contrast, only Th2 cells produced MIP-2. The
      possible biological relevance of these data was substantiated by the finding that
      in vivo-polarized Th1 cells, but not Th2 cells, produced MIP-1gamma and
      lymphotactin while in vivo-polarized Th2 cells secreted MIP-2. The above data
      demonstrate that Th1 and Th2 cells differ in their ability to produce chemokines,
      suggesting that Th1 and Th2 subsets differentially contribute to recruitment of
      cells into inflammatory foci.

PMID- 14573635
TI  - Infection by Trypanosoma cruzi metacyclic forms deficient in gp82 but expressing
      a related surface molecule, gp30.
AB  - Trypanosoma cruzi metacyclic trypomastigotes invade and replicate in the gastric
      mucosal epithelium after oral infection. In this study we analyzed the process of
      infection by T. cruzi isolates deficient in the expression of gp82, the
      metacyclic stage-specific surface glycoprotein implicated in target cell entry in
      vitro and in promoting mucosal infection in mice after oral challenge. Mice
      infected by the oral route with metacyclic forms of gp82-deficient isolate 569 or
      588 developed patent parasitemia but at greatly reduced levels compared to those
      infected with the gp82-expressing isolate CL. Metacyclic forms of both isolates
      expressed gp30, a surface glycoprotein detectable by monoclonal antibody (MAb)
      3F6 directed to gp82. Otherwise, the gp82-deficient isolates displayed a surface
      profile similar to that of the CL isolate and also entered epithelial HeLa cells
      in a manner inhibitable by MAb 3F6 and dependent on the parasite signal
      transduction that involved the activation of protein tyrosine kinase and Ca(2+)
      mobilization from thapsigargin-sensitive stores. Like gp82, gp30 triggered the
      host cell Ca(2+) response required for parasite internalization. Purified gp30
      and the recombinant gp82 inhibited HeLa cell invasion of metacyclic forms of
      isolates 569 and 588 by approximately 90 and approximately 70%, respectively. A
      cell invasion assay performed in the presence of gastric mucin, mimicking the in
      vivo infection, showed an inhibition of 70 to 75% in the internalization of gp82
      deficient isolates but not of the CL isolate. The recombinant gp82 exhibited an
      adhesive capacity toward gastric mucin much higher than that of gp30. Taken
      together, our findings indicate that target cell entry of metacyclic
      trypomastigotes can be mediated either by gp82 or gp30 but that efficient mucosal
      infection depends on the expression of gp82.

PMID- 14573636
TI  - Genetic basis for the structural difference between Streptococcus pneumoniae
      serotype 15B and 15C capsular polysaccharides.
AB  - In a search for the genetic basis for the structural difference between the
      related Streptococcus pneumoniae capsular serotypes 15B and 15C and for the
      reported reversible switching between these serotypes, the corresponding capsular
      polysaccharide synthesis (cps) loci were investigated by keeping in mind that at
      the structural level, the capsules differ only in O acetylation. The cps locus of
      a serotype 15B strain was identified, partially PCR amplified with primers based
      on the related serotype 14 sequence, and sequenced. Sequence analysis revealed,
      among other open reading frames, an intact open reading frame (designated
      cps15bM) whose product, at the protein level, exhibited characteristics of
      previously identified acetyltransferases. Genetic analysis of the corresponding
      region in a serotype15C strain indicated that the same gene was present but had a
      premature stop in translation. Closer analysis indicated that the serotype 15B
      gene contained a short tandem TA repeat consisting of eight TA units. In serotype
      15C, this gene contained nine TA units that resulted in a frameshift and a
      truncated product. Genetic analysis of 17 serotype 15B and 15C clinical isolates
      revealed a perfect correlation between the serotype and the length of the short
      tandem repeat in the putative O-acetyltransferase gene. The number of TA
      repeating units varied between seven and nine in the various isolates. Together,
      the data strongly suggest that the structural difference between serotypes 15B
      and 15C is based on variation in the short tandem TA repeat in the O
      acetyltransferase gene and that the transition between serotypes is due to
      slipped-strand mispairing with deletion or insertion of TA units in the cps15bM
      gene.

PMID- 14573637
TI  - Phage lytic enzyme Cpl-1 as a novel antimicrobial for pneumococcal bacteremia.
AB  - Streptococcus pneumoniae is becoming increasingly antibiotic resistant worldwide,
      and thus new antimicrobials are badly needed. We report the use of Cpl-1, the
      lytic enzyme of a pneumococcal bacteriophage, as an intravenous therapy for
      pneumococcal bacteremia in a mouse model. A 2000- microg dose of Cpl-1 reduced
      pneumococcal titers from a median of log(10) 4.70 CFU/ml to undetectable levels
      (<log(10) 2.00 CFU/ml) within 15 min. This dose given 1 h after intravenous
      infection led to 100% survival at 48 h, compared to the 20% survival of buffer
      treated controls. In advanced bacteremia, treatment with two doses at 5 and 10 h
      still resulted in significantly longer survival (P < 0.0001) and a hazard ratio
      of 0.29 (95% confidence interval, 0.04 to 0.35). The enzyme is immunogenic, but
      the treatment efficacy was not significantly diminished after previous
      intravenous exposure of mice and hyperimmune rabbit serum did not neutralize the
      activity. Cpl-1 is also very effective as a topical nasal treatment against
      colonization by S. pneumoniae. In vitro, the enzyme is active against many
      serotypes of S. pneumoniae, independent of their penicillin resistance, and it is
      very specific for this species. Bacteriophage enzymes are unusual but extremely
      effective antimicrobials and represent a new weapon against infections with
      resistant bacteria.

PMID- 14573638
TI  - Therapeutic activity of an engineered synthetic killer antiidiotypic antibody
      fragment against experimental mucosal and systemic candidiasis.
AB  - Peptides derived from the sequence of a single-chain, recombinant, antiidiotypic
      antibody (IdAb; KT-scFv) acting as a functional internal image of a microbicidal,
      wide-spectrum yeast killer toxin (KT) were synthesized and studied for their
      antimicrobial activity by using the KT-susceptible Candida albicans as model
      organism. A decapeptide containing the first three amino acids (SAS) of the light
      chain CDR1 was selected and optimized by alanine replacement of a single residue.
      This peptide exerted a strong candidacidal activity in vitro, with a 50%
      inhibitory concentration of 0.056 microM, and was therefore designated killer
      peptide (KP). Its activity was neutralized by laminarin, a beta1-3 glucan
      molecule, but not by pustulan, a beta1-6 glucan molecule. KP also competed with
      the binding of a KT-like monoclonal IdAb to germinating cells of the fungus. In a
      rat model of vaginal candidiasis, local, postchallenge administration of KP was
      efficacious in rapidly abating infections caused by fluconazole-susceptible or 
      resistant C. albicans strains. In systemic infection of BALB/c or SCID mice
      preinfected intravenously with a lethal fungal load, KP caused a highly
      significant prolongation of the median survival time, with >80% of the animals
      still surviving after >60 days, whereas >90% of control mice died within 3 to 5
      days. KP is therefore the first engineered peptide derived from a recombinant
      IdAb retaining KT microbicidal activity, probably through the interaction with
      the beta-glucan KT receptor on target microbial cells.

PMID- 14573639
TI  - Absence of the macrophage mannose receptor in mice does not increase
      susceptibility to Pneumocystis carinii infection in vivo.
AB  - Host defense against the opportunistic pathogen Pneumocystis carinii requires
      functional interactions of many cell types. Alveolar macrophages are presumed to
      be a vital host cell in the clearance of P. carinii, and the mechanisms of this
      interaction have come under scrutiny. The macrophage mannose receptor is believed
      to play an important role as a receptor involved in the binding and phagocytosis
      of P. carinii. Although there is in vitro evidence for this interaction, the in
      vivo role of this receptor in P. carinii clearance in unclear. Using a mouse
      model in which the mannose receptor has been deleted, we found that the absence
      of this receptor is not sufficient to allow infection by P. carinii in otherwise
      immunocompetent mice. Furthermore, when mice were rendered susceptible to P.
      carinii by CD4(+) depletion, mannose receptor knockout mice (MR-KO) had pathogen
      loads equal to those of wild-type mice. However, the MR-KO mice exhibited a
      greater influx of phagocytes into the alveoli during infection. This was
      accompanied by increased pulmonary pathology in the MR-KO mice, as well as
      greater accumulation of glycoproteins in the alveoli (glycoproteins, including
      harmful hydrolytic enzymes, are normally cleared by the mannose receptor). We
      also found that the surface expression of the mannose receptor is not
      downregulated during P. carinii infection in wild-type mice. Our findings suggest
      that while the macrophage mannose receptor may be important in the recognition of
      P. carinii, in vivo, this mechanism may be redundant, and the absence of this
      receptor may be compensated for.

PMID- 14573640
TI  - The MIC3 gene of Toxoplasma gondii is a novel potent vaccine candidate against
      toxoplasmosis.
AB  - Infection with the intracellular protozoan parasite Toxoplasma gondii causes
      serious public health problems and is of great economic importance worldwide. The
      micronemal protein MIC3, which is a potent adhesin of T. gondii, could be a
      significant candidate vaccine against toxoplasmosis. In this study, all CBA/J
      mice intramuscularly vaccinated with a plasmid encoding the immature form of the
      MIC3 protein (pMIC3i) produced specific anti-MIC3 immunoglobulin G (IgG)
      antibodies, and their sera displayed high antibody titers. This response was
      increased by the coadministration of a plasmid encoding the granulocyte
      macrophage colony-stimulating factor (pGM-CSF). Similarly, a specific and
      significant cellular immune response was obtained in mice immunized with pMIC3i,
      and this response was markedly enhanced by pGM-CSF coadministration. The cellular
      immune response was associated with the production of gamma interferon IFN-gamma
      and interleukin-2 (IL-2), indicating that this was a Th1-type response. This was
      confirmed by the production of large amounts of IgG2a. Mice immunized with pMIC3i
      displayed significant protection against an oral challenge with T. gondii 76K
      cysts, exhibiting fewer brain cysts than did the control mice. Coadministration
      of pGM-CSF enhanced this protection. In conclusion, this study describes the
      design of a potent DNA vaccine encoding the novel T. gondii target antigen, MIC3
      protein, that elicits a strong specific immune response as well as providing
      effective protection against T. gondii infection. In the attempt to achieve
      complete protection against toxoplasmosis, MIC3 is a good candidate vaccine which
      could be combined with other relevant and previously described candidates, such
      as SAG1 and GRA4.

PMID- 14573641
TI  - Antibodies to Plasmodium falciparum rifin proteins are associated with rapid
      parasite clearance and asymptomatic infections.
AB  - Plasmodium falciparum rifin proteins, belonging to the largest known family of
      variable infected-erythrocyte surface-expressed proteins encoded by rif genes,
      were recently shown to be capable of inducing a strong immune response in P.
      falciparum-infected adults living in an area in Gabon where malaria is endemic.
      In the present study, the levels of antirifin antibodies were analyzed in serum
      obtained from 60 children from the same area who were admitted to hospital and
      diagnosed with severe malaria. High antirifin antibody concentrations in these
      individuals correlated significantly with their capacity to rapidly clear their
      parasites from the circulation after the start of chemotherapy. A doubling of
      antirifin antibody concentrations reduced the clearance time by 5 h (95%
      confidence interval, 4.1 to 6.9 h). In the same group of children, who were
      followed up for 2 years, antirifin antibody levels did not correlate with a
      reduced rate of reinfection or with a delay in the time to the first reinfection.
      However, the initial antirifin antibody levels were sustained over the study
      period. The likelihood that these antibodies could confer a certain degree of
      protection against malaria is supported by our findings of statistically higher
      levels of antirifin antibodies to all four rifin proteins in a group of 42
      asymptomatic parasitemic children.

PMID- 14573642
TI  - Role of cyclooxygenase enzymes in a murine model of experimental cholera.
AB  - Nonsteroidal anti-inflammatory drugs (e.g., indomethacin) inhibit and reduce the
      fluid secretion responses elicited by cholera toxin (CT), but it has not been
      conclusively determined which cyclooxygenase (COX) isoform is involved in CT's
      action. This study evaluated the role of the COX enzymes and their arachidonic
      acid metabolites in experimental cholera. Swiss-Webster mice were dosed with
      celecoxib and rofecoxib and challenged with CT in ligated small intestinal loops,
      and intestinal segments from mice deficient in COX-1 and COX-2 were challenged
      with CT. The effects of CT on fluid accumulation, prostaglandin E(2) production,
      mucosal tissue injury, and markers of oxidative stress were measured. Celecoxib
      and rofecoxib given at 160 micro g per mouse inhibited CT-induced fluid
      accumulation by 48% and 31%, respectively, but there was no significant
      difference among cox-1(-/-) and cox-2(-/-) mice in response to CT compared to
      wild-type controls. CT elevated tissue levels of oxidized glutathione and lipid
      peroxides and elicited small intestinal tissue injury in two of five cox-1(-/-)
      and four of five cox-2(-/-) mice. A role for COX-2 in CT's mechanism of action
      has previously been suggested by the effectiveness of COX-2 inhibitors in
      reducing CT-induced fluid secretion, but CT challenge of COX-1 and COX-2 knockout
      mice did not corroborate the pharmacological data. The results of this study show
      that CT induced oxidative stress in COX-deficient mice and suggest a tissue
      protective role for arachidonic acid metabolites in the small intestine against
      oxidative stress.

PMID- 14573643
TI  - Pathogenic Acanthamoeba spp secrete a mannose-induced cytolytic protein that
      correlates with the ability to cause disease.
AB  - The pathogenesis of Acanthamoeba keratitis begins when Acanthamoeba trophozoites
      bind specifically to mannosylated glycoproteins upregulated on the surfaces of
      traumatized corneal epithelial cells. When Acanthamoeba castellanii trophozoites
      are grown in methyl-alpha-D-mannopyranoside, they are induced to secrete a novel
      133-kDa protein that is cytolytic to corneal epithelial cells. Clinical isolates
      of Acanthamoeba spp., and not the soil isolates, were proficient at producing a
      mannose-induced protein (MIP-133) and generating disease in Chinese hamsters. The
      purified protein was efficient at killing corneal epithelial cells, the first
      mechanistic barrier, by inducing apoptosis in a caspase 3-dependent pathway.
      Subsequent steps in pathogenesis require the amoebae to penetrate and degrade
      collagen. Only the clinical isolates tested were efficient at migrating through a
      collagenous matrix in vitro, presumably by MIP-133 degradation of both human type
      I and human type IV collagen. A chicken anti-MIP-133 antiserum effectively bound
      to the protein and blocked collagenolytic activity, migration, and cytopathic
      effects (CPE) against corneal cells in vitro. Chinese hamsters orally immunized
      with MIP-133 displayed a >30% reduction in disease. Immunoglobulin A isolated
      from immunized animals bound MIP-133 and blocked CPE on corneal cells in vitro.
      Animals induced to generate severe chronic infections displayed significant
      reductions in disease symptoms upon oral immunization postinfection. These data
      suggest that MIP-133 production might be necessary to initiate corneal disease
      and that it may play an important role in the subsequent steps of the pathogenic
      cascade of Acanthamoeba keratitis. Furthermore, as antibodies produced both prior
      to and after infection reduced clinical symptoms of disease, the protein may
      represent an important immunotherapeutic target for Acanthamoeba keratitis.

PMID- 14573644
TI  - Identification of a gene that affects the efficiency of host cell infection by
      Legionella pneumophila in a temperature-dependent fashion.
AB  - The ability to infect host cells is critical for the survival and replication of
      intracellular pathogens in humans. We previously found that many genes involved
      in the ability of Legionella pneumophila to infect macrophages are not expressed
      efficiently under standard laboratory growth conditions. We have developed an
      approach using expression of L. pneumophila genes from an exogenous constitutive
      promoter on a low-copy-number vector that allows identification of genes involved
      in host cell infection. Through the use of this strategy, we found that
      expression of a gene, lvhB2, enhances the efficiency of L. pneumophila infection
      of mammalian cells. The putative protein encoded by lvhB2 has similarity to
      structural pilin subunits of type IV secretion systems. We confirmed that this
      gene plays a role in host cell infection by the construction of an in-frame
      deletion in the L. pneumophila lvhB2 gene and complementation of this mutant with
      the wild-type gene. The lvhB2 mutant does not display a very obvious defect in
      interactions with host cells when the bacteria are grown at 37 degrees C, but it
      has an approximately 100-fold effect on entry and intracellular replication when
      grown at 30 degrees C. These data suggest that lvhB2 plays an important role in
      the efficiency of host cell infection by L. pneumophila grown at lower
      temperatures.

PMID- 14573645
TI  - Evaluation of Brucella abortus phosphoglucomutase (pgm) mutant as a new live
      rough-phenotype vaccine.
AB  - Brucella abortus S19 is the vaccine most frequently used against bovine
      brucellosis. Although it induces good protection levels, it cannot be
      administered to pregnant cattle, revaccination is not advised due to interference
      in the discrimination between infected and vaccinated animals during immune
      screening procedures, and the vaccine is virulent for humans. Due to these
      reasons, there is a continuous search for new bovine vaccine candidates that may
      confer protection levels comparable to those conferred by S19 but without its
      disadvantages. A previous study characterized the phenotype associated with the
      phosphoglucomutase (pgm) gene disruption in Brucella abortus S2308, as well as
      the possible role for the smooth lipopolysaccharide (LPS) in virulence and
      intracellular multiplication in HeLa cells (J. E. Ugalde, C. Czibener, M. F.
      Feldman, and R. A. Ugalde, Infect. Immun. 68:5716-5723, 2000). In this report, we
      analyze the protection, proliferative response, and cytokine production induced
      in BALB/c mice by a deltapgm deletion strain. We show that this strain
      synthesizes O antigen with a size of approximately 45 kDa but is rough. This is
      due to the fact that the deltapgm strain is unable to assemble the O side chain
      in the complete LPS. Vaccination with the deltapgm strain induced protection
      levels comparable to those induced by S19 and generated a proliferative
      splenocyte response and a cytokine profile typical of a Th1 response. On the
      other hand, we were unable to detect a specific anti-O-antigen antibody response
      by using the fluorescence polarization assay. In view of these results, the
      possibility that the deltapgm mutant could be used as a vaccination strain is
      discussed.

PMID- 14573646
TI  - DNA immunization with the gene encoding P4 nuclease of Leishmania amazonensis
      protects mice against cutaneous Leishmaniasis.
AB  - Infection with the protozoan parasite Leishmania amazonensis can cause diverse
      clinical forms of leishmaniasis. Immunization with purified P4 nuclease protein
      has been shown to elicit a protective response in mice challenged with L.
      amazonensis and L. pifanoi. To explore the potential of a DNA-based vaccine, we
      tested the L. amazonensis gene encoding P4 nuclease as well as adjuvant
      constructs encoding murine interleukin-12 (IL-12) and L. amazonensis HSP70.
      Susceptible BALB/c mice were immunized with the DNA encoding P4 alone, P4/IL-12,
      or P4/HSP70 prior to challenge with L. amazonensis promastigotes. Mice given
      P4/IL-12 exhibited no lesion development and had a 3- to 4-log reduction in
      tissue parasite burdens compared to controls. This protection corresponded to
      significant increases in gamma interferon and tumor necrosis factor alpha
      production and a reduction in parasite-specific immunoglobulin G1, suggesting an
      enhancement in Th1 responses. Moreover, we immunized mice with the L. amazonensis
      vaccines to determine if this vaccine regimen could provide cross-protection
      against a genetically diverse species, L. major. While the P4/HSP70 vaccine led
      to self-healing lesions, the P4/IL-12 vaccine provided negligible protection
      against L. major infection. This is the first report of successful use of a DNA
      vaccine to induce protection against L. amazonensis infection. Additionally, our
      results indicate that different vaccine combinations, including DNA encoding P4,
      HSP70, or IL-12, can provide significant protection against both Old World and
      New World cutaneous leishmaniasis.

PMID- 14573647
TI  - Low-level pilin expression allows for substantial DNA transformation competence
      in Neisseria gonorrhoeae.
AB  - The gonococcal pilus is a major virulence factor that has well-established roles
      in mediating epithelial cell adherence and DNA transformation. Gonococci
      expressing four gonococcal pilin variants with distinct piliation properties
      under control of the lac regulatory system were grown in different levels of the
      inducer isopropyl-beta-D-thiogalactopyranoside (IPTG). These pilin variants
      expressed various levels of pilin message and pilin protein in response to the
      level of IPTG in the growth medium. Moreover, posttranslational modifications of
      the variant pilin proteins were detected, including S-pilin production and
      glycosylation. The ratio of the modified and unmodified pilin forms did not
      substantially change with different levels of pilin expression, showing that
      these modifications are not linked to pilin expression levels. DNA transformation
      competence was also influenced by IPTG levels in the growth medium. Substantial
      increases in transformation competence over an isogenic, nonpiliated mutant were
      observed when limited amounts of three of the pilin variants were expressed.
      Immunoelectron microscopy showed that when limited amounts of pilin are
      expressed, pili are rare and do not explain the pilin-dependent transformation
      competence. This pilin-dependent transformation competence required prepilin
      processing, the outer membrane secretin PilQ, and the twitching-motility
      regulating protein PilT. These requirements show that a fully functional pilus
      assembly apparatus is required for DNA uptake when limited pilin is produced. We
      conclude that the pilus assembly apparatus functions to import DNA into the
      bacterial cell in a pilin-dependent manner but that extended pili are not
      required for transformation competence.

PMID- 14573648
TI  - New rat model of Pneumocystis pneumonia induced by anti-CD4(+) T-lymphocyte
      antibodies.
AB  - The CD4(+) T lymphocyte plays a central role in host defense against Pneumocystis
      pneumonia but has received only limited attention in rats. CD4(+) T-cell
      depleting (OX-38) and nondepleting (W3/25) monoclonal antibodies, which recognize
      an identical or adjacent epitope, were administered for up to 14 weeks to Lewis
      rats that had been exposed to PNEUMOCYSTIS: While OX-38 produced a greater
      decrease in circulating CD4(+) cells than W3/25, both antibody treatments
      resulted in similar effects on the health of the rats and the levels of
      Pneumocystis pneumonia, which were milder than those found with corticosteroids.
      W3/25 also did not enhance the severity of Pneumocystis pneumonia achieved with
      corticosteroids alone. We conclude that CD4(+) cell function is more important
      than CD4(+) cell number in host defense against Pneumocystis in the rat and that
      this new model permits study of opportunistic infections in the rat without the
      confounding effects of corticosteroids.

PMID- 14573650
TI  - Transfer region of pO113 from enterohemorrhagic Escherichia coli: similarity with
      R64 and identification of a novel plasmid-encoded autotransporter, EpeA.
AB  - Enterohemorrhagic Escherichia coli (EHEC) is a prominent, food-borne cause of
      diarrhea, bloody diarrhea, and the hemolytic uremic syndrome in industrialized
      countries. Most strains of EHEC carry the locus for enterocyte effacement (LEE)
      pathogenicity island, but a proportion of isolates from patients with severe
      disease do not carry LEE and very little is known about virulence factors in
      these organisms. LEE-negative strains of EHEC typically express Shiga toxin 2 and
      carry a large plasmid that encodes the production of EHEC hemolysin. In this
      study, we determined the nucleotide sequence of the transfer region of pO113, the
      large hemolysin plasmid from LEE-negative EHEC O113:H21 (EH41). This 63.9-kb
      region showed a high degree of similarity with the transfer region of R64, and
      pO113 was capable of self-transmission at low frequencies. Unlike R64 and the
      related dot/icm system of Legionella pneumophila, however, pO113 was unable to
      mobilize RSF1010. In addition, the pO113 transfer region encoded a novel high
      molecular-weight serine protease autotransporter of Enterobacteriaceae (SPATE)
      protein, termed EpeA. Like other SPATEs, EpeA exhibited protease activity and
      mucinase activity, but expression was not associated with a cytopathic effect on
      epithelial cells. Analysis of a second high-molecular-weight secreted protein
      revealed that pO113 also encodes EspP, a cytopathic SPATE identified previously
      in EHEC O157:H7. The nucleotide sequences encoding the predicted beta-domains of
      espP and epeA were identical and also shared significant homology with a third
      SPATE protein, EspI. Both espP and epeA were detected in several LEE-negative
      clinical isolates of EHEC and thus may contribute to the pathogenesis of this
      subset of EHEC.

PMID- 14573649
TI  - Comparison of two major forms of the Shigella virulence plasmid pINV: positive
      selection is a major force driving the divergence.
AB  - All Shigella and enteroinvasive Escherichia coli (EIEC) strains carry a 230-kb
      virulence plasmid (pINV) which is essential for their invasiveness. There are two
      sequence forms, pINV A and pINV B, of the plasmid (R. Lan, B. Lumb, D. Ryan, and
      P. R. Reeves, Infect. Immun. 69:6303-6309, 2001), and the recently sequenced pINV
      plasmid from Shigella flexneri serotype 5 is a pINV B form. In this study we
      sequenced the majority of the coding region of the pINV A form from S. flexneri
      serotype 6 other than insertion sequence or related sequences and compared it
      with the pINV B form. More than half of the genes sequenced appear to be under
      positive selection based on their low ratio of synonymous to nonsynonymous
      substitutions. This high proportion of selected differences indicates that the
      two pINV forms have functional differences, and comparative studies of
      pathogenicity in different Shigella-EIEC strains could be informative. There are
      also genes absent in the S. flexneri serotype 6 plasmid, including the sepA gene
      encoding serine protease, the major secreted protein of S. flexneri serotype 2a,
      and the stbAB genes, which encode one of the two partition systems found in S.
      flexneri serotype 5. The incompatibility of the two pINV forms appears to be due
      to either small differences in the mvpAT postsegregational killing system or the
      presence of an unknown system in pINVA.

PMID- 14573651
TI  - Autodisplay: efficacious surface exposure of antigenic UreA fragments from
      Helicobacter pylori in Salmonella vaccine strains.
AB  - Live attenuated Salmonella strains expressing antigens of pathogens are promising
      oral vaccine candidates. There is growing evidence that the topology of
      expression of the foreign antigens can have a dramatic impact on the
      immunogenicity. We examined the potential of the AIDA-I (Escherichia coli adhesin
      involved in diffuse adherence) autotransporter domain to display antigenic
      fragments of the urease A subunit of Helicobacter pylori for the induction of a
      protective immune response. In the murine H. pylori model, protection is mainly
      mediated by CD4(+) T cells, and we therefore used the AIDA-I expression system to
      successfully express both nearly full-length UreA and defined T-helper-cell
      epitopes on the surface of an attenuated Salmonella enterica serovar Typhimurium
      vaccine strain. Surface exposure of the large UreA fragment or of one UreA T-cell
      epitope mediated a significant reduction in the level of H. pylori in immunized
      mice after challenge infection, whereas conventional cytoplasmic expression of
      UreA in Salmonella had no effect. These results support the concept that surface
      display increases the immunogenicity of recombinant antigens expressed on oral
      live vaccine carriers and further demonstrate the feasibility of immunizing
      against H. pylori with Salmonella vaccine strains expressing CD4(+) T-cell
      epitopes.

PMID- 14573652
TI  - Rhodococcus equi secreted antigens are immunogenic and stimulate a type 1 recall
      response in the lungs of horses immune to R. equi infection.
AB  - Rhodococcus equi is an opportunistic pathogen in immunocompromised humans and an
      important primary pathogen in young horses. Although R. equi infection can
      produce life-threatening pyogranulomatous pneumonia, most foals develop a
      protective immune response that lasts throughout life. The antigen targets of
      this protective response are currently unknown; however, Mycobacterium
      tuberculosis is a closely related intracellular pathogen and provides a model
      system. Based on previous studies of M. tuberculosis protective antigens released
      into culture filtrate supernatant (CFS), a bacterial growth system was developed
      for obtaining R. equi CFS antigens. Potential immunogens for prevention of equine
      rhodococcal pneumonia were identified by using immunoblots. The 48-h CFS
      contained five virulence-associated protein bands that migrated between 12 and 24
      kDa and were recognized by sera from R. equi-infected foals and immune adult
      horses. Notably, the CFS contained the previously characterized proteins VapC,
      VapD, and VapE, which are encoded by genes on the R. equi virulence plasmid. R.
      equi CFS was also examined for the ability to stimulate a type 1-like memory
      response in immune horses. Three adult horses were challenged with virulent R.
      equi, and cells from the bronchoalveolar lavage fluid were recovered before and 1
      week after challenge. In vitro stimulation of pulmonary T-lymphocytes with R.
      equi CFS resulted in significant proliferation and a significant increase in
      gamma interferon mRNA expression 1 week after challenge. These results were
      consistent with a memory effector response in immune adult horses and provide
      evidence that R. equi CFS proteins are antigen targets in the immunoprotective
      response against R. equi infection.

PMID- 14573653
TI  - PPE antigen Rv2430c of Mycobacterium tuberculosis induces a strong B-cell
      response.
AB  - The variation in sequence and length in the C-terminal region among members of
      the unique PE (Pro-Glu) and PPE (Pro-Pro-Glu) protein families of Mycobacterium
      tuberculosis is a likely source of antigenic variation, giving rise to the
      speculation that these protein families could be immunologically important. Based
      on in silico analysis, we selected a hypothetical open reading frame (ORF)
      encoding a protein belonging to the PPE family and having epitopes with
      predictably higher antigenic indexes. Reverse transcriptase PCR using total RNA
      extracted from in vitro-cultured M. tuberculosis H37Rv generated an mRNA product
      corresponding to this gene, indicating the expression of this ORF (Rv2430c) at
      the mRNA level. Recombinant protein expressed in Escherichia coli was used to
      screen the sera of M. tuberculosis-infected patients, as well as those of
      clinically healthy controls (n = 10), by enzyme-linked immunosorbent assay. The
      panel of patient sera comprised sera from fresh infection cases (category 1; n =
      32), patients with relapsed tuberculosis (category 2; n = 30), and extrapulmonary
      cases (category 3; n = 30). Category 2 and 3 sera had strong antibody responses
      to the PPE antigen, equal to or higher than those to other well-known antigens,
      such as Hsp10 or purified protein derivative (PPD). However, a higher percentage
      of patients belonging to category 1, as opposed to clinically healthy controls,
      showed stronger antibody response against the PPE protein when probed with anti
      immunoglobulin M (IgM) (71 versus 37.5%) or anti-IgG (62.5 versus 28.12%). Our
      results reveal that this PPE ORF induces a strong B-cell response compared to
      that generated by M. tuberculosis Hsp10 or PPD, pointing to the immunodominant
      nature of the protein.

PMID- 14573655
TI  - Plasma interleukin-12 in malaria-tolerant papua new guineans: inverse correlation
      with Plasmodium falciparum parasitemia and peripheral blood mononuclear cell
      nitric oxide synthase activity.
AB  - Interleukin-12 (IL-12) has been inversely associated with disease severity in
      human and murine malaria, and a polymorphism in the IL-12 p40 subunit gene
      (IL12B) has been associated with susceptibility to human cerebral malaria and
      reduced nitric oxide (NO) production. To better define the relationships between
      IL-12, NO, malaria parasitemia, and IL12B polymorphisms during malarial
      tolerance, plasma IL-12 levels and peripheral blood mononuclear cell NO synthase
      (NOS) activity were measured in asymptomatic Papua New Guineans exposed to
      intense malaria transmission. The IL-12 level was strongly inversely correlated
      with the density of Plasmodium falciparum parasitemia (rho = -0.45; P < 0.001)
      and was predicted to decrease by 19% (95% confidence interval [CI], 10 to 27%)
      for each twofold increase in P. falciparum parasitemia. This is consistent with a
      suppressive effect of parasitemia on IL-12 production, an effect previously shown
      in vitro and in rodent models of disease. The IL-12 level was inversely
      correlated with NOS activity (r = -0.22; P = 0.007), with each twofold increase
      in NOS activity being predictive of a 25% (95% CI, 7 to 38%) decrease in plasma
      IL-12 levels. This probably reflects additional down-regulation of IL-12 by the
      high basal NO production and monocyte NOS expression found in the malaria
      tolerant state. Neither the IL-12 level nor NOS activity was associated with
      either of two IL12B polymorphisms, reflecting the diversity of genetic control
      over immune responses in different populations.

PMID- 14573654
TI  - Critical role of the complement system in group B streptococcus-induced tumor
      necrosis factor alpha release.
AB  - Group B Streptococcus (GBS) is a major cause of newborn sepsis and meningitis and
      induces systemic release of tumor necrosis factor alpha (TNF-alpha), believed to
      play a role in morbidity and mortality. While previous studies have shown that
      GBS can induce TNF-alpha release from monocytes and macrophages, little is known
      about the potential modulating effect of plasma or serum on GBS-induced TNF-alpha
      release, and there are conflicting reports as to the host receptors involved. In
      a human whole-blood assay system, GBS type III COH-1 potently induced substantial
      monocyte TNF-alpha release in adult peripheral blood and, due to a higher
      concentration of monocytes, 10-fold-greater TNF-alpha release in newborn cord
      blood. Remarkably, GBS-induced TNF-alpha release from human monocytes was
      enhanced approximately 1000-fold by heat-labile serum components. Experiments
      employing C2-, C3-, or C7-depleted serum demonstrated that C3 activation via the
      alternative pathway is crucial for potent GBS-induced TNF-alpha release.
      Accordingly, whole blood from C3-deficient mice demonstrated significantly
      reduced GBS-induced TNF-alpha release. Preincubation with human serum enhanced
      the TNF-alpha-inducing activity of GBS in a C3- and factor B-dependent manner,
      implying deposition of complement components via the alternative pathway. GBS
      induced TNF-alpha release was inhibited by monoclonal antibodies directed against
      each of the components of CR3 and CR4: the common integrin beta subunit CD18 and
      the alpha subunits CD11b (of CR3) and CD11c (of CR4). Blood derived from CR3
      (CD11b/CD18)-deficient mice demonstrated a markedly diminished TNF-alpha response
      to GBS. We conclude that the ability of plasma and serum to greatly amplify GBS
      induced TNF-alpha release reflects the activity of the alternative complement
      pathway that deposits fragments on GBS and thereby enhances CR3- and CR4-mediated
      monocyte activation.

PMID- 14573656
TI  - Pertussis toxin plays an early role in respiratory tract colonization by
      Bordetella pertussis.
AB  - In this study, we sought to determine whether pertussis toxin (PT), an exotoxin
      virulence factor produced exclusively by Bordetella pertussis, is important for
      colonization of the respiratory tract by this pathogen by using a mouse
      intranasal infection model. By comparing a wild-type Tohama I strain to a mutant
      strain with an in-frame deletion of the ptx genes encoding PT (deltaPT), we found
      that the lack of PT confers a significant peak (day 7) colonization defect (1 to
      2 log(10) units) over a range of bacterial inoculum doses and that this defect
      was apparent within 1 to 2 days postinoculation. In mixed-strain infection
      experiments, the deltaPT strain showed no competitive disadvantage versus the
      wild-type strain and colonized at higher levels than in the single-strain
      infection experiments. To test the hypothesis that soluble PT produced by the
      wild-type strain in mixed infections enhanced respiratory tract colonization by
      deltaPT, we coadministered purified PT with the deltaPT inoculum and found that
      colonization was increased to wild-type levels. This effect was not observed when
      PT was coadministered via a systemic route. Intranasal administration of purified
      PT up to 14 days prior to inoculation with deltaPT significantly increased
      bacterial colonization, but PT administration 1 day after bacterial inoculation
      did not enhance colonization versus a phosphate-buffered saline control. Analysis
      of bronchoalveolar lavage fluid samples from mice infected with either wild-type
      or deltaPT strains at early times after infection revealed that neutrophil influx
      to the lungs 48 h postinfection was significantly greater in response to deltaPT
      infection, implicating neutrophil chemotaxis as a possible target of PT activity
      promoting B. pertussis colonization of the respiratory tract.

PMID- 14573657
TI  - Relative immunogenicity of PorA subtypes in a multivalent Neisseria meningitidis
      vaccine is not dependent on presentation form.
AB  - The hexavalent meningococcal vaccine HexaMen, containing six PorAs on two
      vesicles, was tested in clinical studies. Although fourfold increases in serum
      bactericidal activity (SBA) titers against all of the PorAs were observed, there
      were significant differences between PorA-specific SBA titers. SBA titers were
      mainly directed against one PorA from each vesicle, P1.5-2,10 and P1.5-1,2-2, and
      were lower against the other PorAs, especially P1.7-2,4 and P1.19,15-1. We
      investigated whether these differences were due to immunological interference
      that resulted in competition between the three PorAs on the same vesicle or
      whether they were caused by a difference in the immunogenicities of the separate
      PorAs. Therefore, mice were immunized either with HexaMen, with six monovalent
      outer membrane vesicles (OMVs) representing the same six PorAs simultaneously
      (HexaMix), or with only one of the monovalent OMVs. The immunoglobulin G and SBA
      titers after HexaMen immunization in mice resembled the results obtained in
      clinical studies. Although immunization with HexaMix gave higher titers than
      immunization with HexaMen for some PorAs, the pattern of high and low titers was
      the same. Similar differences in immunogenicity between subtypes were seen after
      monovalent immunization when interference was eliminated as a cause of the
      differences. Monovalent immunization resulted in higher titers for P1.5-1,2-2 and
      P1.7,16 than immunization with HexaMen. However, no significant differences were
      found for the weakly immunogenic PorAs, P1.7-2,4 and P1.19,15-1. Since
      immunization with the six PorAs in the trivalent presentation form (HexaMen) and
      in the mixture of monovalent vesicles (HexaMix) resulted in the same pattern of
      high and low titers, we concluded that the differences between the PorA-specific
      responses are due to differences in the immunogenicities of the various PorAs and
      not due to interference that results in competition between different PorAs.

PMID- 14573658
TI  - DNA vaccination protects mice against challenge with Listeria monocytogenes
      expressing the hepatitis C virus NS3 protein.
AB  - The goal of this study was to develop a new surrogate challenge model for use in
      evaluating protective cell-mediated immune responses against hepatitis C virus
      (HCV) antigens. The use of recombinant Listeria monocytogenes organisms which
      express HCV antigens provides novel tools with which to assay such in vivo
      protection, as expression of immunity against this hepatotropic bacterial
      pathogen is dependent on antigen-specific CD8(+) T lymphocytes. A plasmid DNA
      vaccine encoding a ubiquitin-NS3 fusion protein was generated, and its efficacy
      was confirmed by in vivo induction of NS3-specific, gamma interferon-secreting T
      cells following vaccination of BALB/c mice. These immunized mice also exhibited
      specific in vivo protection against subsequent challenge with a recombinant L.
      monocytogenes strain (TC-LNS3) expressing the NS3 protein. Notably, sublethal
      infection of naive mice with strain TC-LNS3 induced similar NS3-specific T-cell
      responses. These findings suggest that recombinant strains of L. monocytogenes
      expressing HCV antigens should prove useful for evaluating, or even inducing,
      protective immune responses against HCV antigens.

PMID- 14573659
TI  - Gonococcal phospholipase d modulates the expression and function of complement
      receptor 3 in primary cervical epithelial cells.
AB  - CR3-mediated endocytosis is a primary mechanism by which Neisseria gonorrhoeae
      elicits membrane ruffling and cellular invasion of the cervical epithelia. Our
      data indicate that, upon infection of cervical epithelia, N. gonorrhoeae
      specifically releases proteins, including a phospholipase D (PLD) homolog, which
      facilitate membrane ruffling. To elucidate the function of gonococcal PLD in
      infection of the cervical epithelia, we constructed an N. gonorrhoeae PLD mutant.
      By comparative association and/or invasion assays, we demonstrated that PLD
      mutant gonococci are impaired in their ability to adhere to and to invade primary
      cervical cells. This defect can be rescued by the addition of supernatants
      obtained from wild-type-infected cell monolayers but not by exogenously added
      Streptomyces PLD. The decreased level of total cell association (i.e., adherence
      and invasion) observed for mutant gonococci is, in part, attributed to the
      inability of these bacteria to recruit CR3 to the cervical cell surface with
      extended infection. Using electron microscopy, we demonstrate that gonococcal PLD
      may be necessary to potentiate membrane ruffling and clustering of gonococci on
      the cervical cell surface. These data may be indicative of the inability of PLD
      mutant gonococci to recruit CR3 to the cervical cell surface. Alternatively, in
      the absence of gonococcal PLD, signal transduction events required for CR3
      clustering may not be activated. Collectively, our data indicate that PLD
      augments CR3-mediated gonococcus invasion of and survival within cervical
      epithelia.

PMID- 14573661
TI  - Inhibition of the complement membrane attack complex by Schistosoma mansoni
      paramyosin.
AB  - Larvae and adults of the parasitic blood fluke Schistosoma mansoni are resistant
      to killing by human complement. An earlier search by Parizade et al. for a
      schistosome complement inhibitor identified a 94-kDa surface protein which was
      named SCIP-1 (M. Parizade, R. Arnon, P. J. Lachmann, and Z. Fishelson, J. Exp.
      Med. 179:1625-1636, 1994). Following partial purification and analysis by mass
      spectrometry, we have determined SCIP-1 to be a surface-exposed form of the
      muscle protein paramyosin. As shown by immunofluorescence, anti-paramyosin
      antibodies label the surface of live schistosomula and adult worms. Like SCIP-1,
      purified native paramyosin reacts with a polyclonal rabbit anti-human CD59
      antiserum, as shown by Western blot analysis. Also, the human complement
      components C8 and C9 bind to recombinant and native paramyosin. Analysis of
      paramyosin binding to fragments of C9 generated by thrombin or trypsin has
      demonstrated that paramyosin binds to C9 at a position located between Gly245 and
      Arg391. Paramyosin inhibited Zn(2+)-induced C9 polymerization and poly-C9
      deposition onto rabbit erythrocytes (E(R)). In addition, paramyosin inhibited
      lysis of E(R) and of sensitized sheep erythrocytes by human complement. Finally,
      anti-paramyosin antibodies enhanced in vitro killing of schistosomula by normal
      and C4-depleted human complement. Taken together, these findings suggest that an
      exogenous form of S. mansoni paramyosin inhibits activation of the terminal
      pathway of complement and thus has an important immunomodulatory role in
      schistosomiasis.

PMID- 14573660
TI  - Role of cytokines and major histocompatibility complex restriction in mouse
      resistance to infection with a natural recombinant strain (type I-III) of
      Toxoplasma gondii.
AB  - Herein we characterized various genetic markers and the biological behavior of a
      natural recombinant strain of Toxoplasma gondii (P-Br). From nine genetic markers
      analyzed, three (B1, ROP1, and SAG1) and three (cS10-A6, GRA6, and SAG3) markers
      belong to parasites from the type I and type III lineages, respectively. The SAG2
      and L363 loci were shown to be type I-III chimera alleles. The cB2l-4
      microsatellite marker showed a unique haplotype. The P-Br strain presented low
      virulence in the acute phase of infection and was cystogenic during the chronic
      infection. The interleukin 12/gamma interferon axis and inducible nitric oxide
      synthase were main determinants of resistance during the acute infection with the
      P-Br strain. As opposed to infection with the type II strain of T. gondii (ME
      49), peroral infection with the P-Br strain led only to a light inflammatory
      infiltrate and no major lesions in the intestine of the C57BL/6 mice. In
      addition, the BALB/c (resistant to ME-49) and C57BL/6 (susceptible to ME-49) mice
      were shown, respectively, to be more susceptible and more resistant to cyst
      formation and toxoplasmic encephalitis when infected with the P-Br strain.
      Further, the C57BL/KsJ and DBA2/J congenic strains containing major
      histocompatibility complex (MHC) haplotype "d" were more resistant than the
      parental strains (C57BL/6 and DBA1/J), when infected with the ME-49 but not with
      the P-Br strain. Together, our results indicate that resistance to cyst formation
      and toxoplasmic encephalitis induced during infection with P-Br is not primarily
      controlled by the MHC haplotype d, as previously reported for type II strains of
      T. gondii.

PMID- 14573662
TI  - Revaccination of neonatal calves with Mycobacterium bovis BCG reduces the level
      of protection against bovine tuberculosis induced by a single vaccination.
AB  - Cattle may provide a suitable model for testing ways of improving tuberculosis
      vaccine efficacy in human infants. A vaccination and challenge study was
      undertaken in calves to determine the optimal time to vaccinate neonatal animals
      with Mycobacterium bovis bacillus Calmette-Guerin (BCG) for protection against
      tuberculosis and to determine whether revaccination with BCG was beneficial.
      Calves (10 per group) were vaccinated with BCG within 8 h of birth or at 6 weeks
      of age, when immune responses to antigens of environmental mycobacteria were
      detectable, or vaccinated at birth and revaccinated at 6 weeks. A control group
      was not vaccinated. BCG vaccination at birth induced strong antigen-specific
      gamma interferon (IFN-gamma) and interleukin-2 (IL-2) responses and antigen
      specific activation in CD4(+), CD8(+), and WC1(+) gammadelta T-cell subsets from
      blood. The proportions of animals per group with macroscopic tuberculous lesions
      after challenge were 0/10 for BCG at birth, 1/9 for BCG at 6 weeks, 4/10 for the
      revaccinated group, and 10/10 for the nonvaccinated group. There was no
      significant difference in the levels of protection between groups vaccinated at
      birth or at 6 weeks, while animals vaccinated both at birth and at 6 weeks had
      significantly less protection than those vaccinated only at birth. The
      revaccinated calves that subsequently developed tuberculous lesions had
      significantly stronger IFN-gamma and IL-2 responses to bovine purified protein
      derivative after the BCG booster than those in the same group that did not
      develop lesions. The results indicated that BCG vaccination at birth induced a
      high level of immunity and that the sensitization of very young animals to
      antigens of environmental mycobacteria by 6 weeks of age did not affect the
      effectiveness of BCG. However, BCG revaccination of these young animals was
      contraindicated.

PMID- 14573663
TI  - Modulation of the bovine delayed-type hypersensitivity responses to defined
      mycobacterial antigens by a synthetic bacterial lipopeptide.
AB  - The use of defined protein and peptide antigens can overcome specificity
      limitations of purified protein derivatives in the detection of bovine
      tuberculosis when the antigens are used in blood-based tests. Since the use of
      these specific antigens as skin test reagents could have practical advantages, we
      investigated the potential of Mycobacterium bovis-specific antigens to stimulate
      delayed-type hypersensitivity (DTH) responses in cattle experimentally infected
      with M. bovis. A cocktail of the recombinant antigens ESAT-6, MPB83, and MPB64
      failed to stimulate in vivo DTH in cattle that had been experimentally infected
      with M. bovis despite the fact that the antigens were recognized in vitro by the
      same animals. However, it was possible to stimulate antigen-specific bovine DTH
      responses by using ESAT-6 in combination with a synthetic bacterial lipopeptide.
      This lipopeptide stimulated the release of the proinflammatory cytokine tumor
      necrosis factor alpha from monocyte-derived bovine dendritic cells in vitro,
      thereby providing a possible mechanism for its DTH-enhancing properties.

PMID- 14573664
TI  - Identification of a 3-deoxy-D-manno-octulosonic acid biosynthetic operon in
      Moraxella catarrhalis and analysis of a KdsA-deficient isogenic mutant.
AB  - Lipooligosaccharide (LOS), a predominant surface-exposed component of the outer
      membrane, has been implicated as a virulence factor in the pathogenesis of
      Moraxella catarrhalis infections. However, the critical steps involved in the
      biosynthesis and assembly of M. catarrhalis LOS currently remain undefined. In
      this study, we used random transposon mutagenesis to identify a 3-deoxy-D-manno
      octulosonic acid (KDO) biosynthetic operon in M. catarrhalis with the gene order
      pyrG-kdsA-eno. The lipid A-KDO molecule serves as the acceptor onto which a
      variety of glycosyl transferases sequentially add the core and branch
      oligosaccharide extensions for the LOS molecule. KdsA, the KDO-8-phosphate
      synthase, catalyzes the first step of KDO biosynthesis and is an essential enzyme
      in gram-negative enteric bacteria for maintenance of bacterial viability. We
      report the construction of an isogenic M. catarrhalis kdsA mutant in strain 7169
      by allelic exchange. Our data indicate that an LOS molecule consisting only of
      lipid A and lacking KDO glycosylation is sufficient to sustain M. catarrhalis
      survival in vitro. In addition, comparative growth and susceptibility assays were
      performed to assess the sensitivity of 7169kdsA11 compared to that of the
      parental strain. The results of these studies demonstrate that the native LOS
      molecule is an important factor in maintaining the integrity of the outer
      membrane and suggest that LOS is a critical component involved in the ability of
      M. catarrhalis to resist the bactericidal activity of human sera.

PMID- 14573665
TI  - Human neutrophil chemotaxis is modulated by capsule and O antigen from an
      extraintestinal pathogenic Escherichia coli strain.
AB  - Gram-negative enteric bacilli, such as Escherichia coli, are common causes of
      nosocomial pneumonia. The interaction between pulmonary neutrophils and the
      infecting pathogen is a critical step in determining the outcome. Previous
      studies from our laboratory, for which a rat model of pneumonia was used,
      established that pulmonary neutrophil recruitment was modulated by the E. coli
      virulence factors capsule and O-specific antigen. To begin to understand the
      mechanism by which this recruitment occurs, we conducted in vitro and ex vivo
      chemotaxis assays, for which we used a clinically relevant E. coli isolate (CP9)
      and isogenic derivatives that were deficient in only the O antigen (CP921) or
      capsule (CP9.137) as chemoattractants with or without the high-affinity N
      formylmethionyl-leucyl-phenylalanine receptor antagonist N-tert-butoxycarbonyl
      methionine-leucine-phenylalanine (N-t-BOC). Given that only live E. coli was used
      for the initial in vitro chemotaxis assays, it was predicted that only N-t-BOC
      sensitive chemotaxis would occur. However, both N-t-BOC-sensitive and 
      insensitive chemotaxis was observed. N-t-BOC-insensitive chemotaxis was mediated
      in part by interleukin 8, which was produced by neutrophils that had migrated
      toward E. coli. N-t-BOC-insensitive chemotaxis was only observed when live E.
      coli bacteria, not cell-free E. coli culture supernatants, were used as
      chemoattractants, suggesting that a direct E. coli-neutrophil interaction was
      necessary. The presence of both capsule and O antigen diminished total, N-t-BOC
      sensitive, and N-t-BOC-insensitive neutrophil chemotaxis in vitro. The presence
      of capsule significantly decreased total, N-t-BOC-sensitive, and N-t-BOC
      insensitive neutrophil chemotaxis ex vivo when cell-free bronchoalveolar lavage
      fluid from infected rats was used as the source of chemotactic factors. These
      effects of E. coli capsule and O antigen on neutrophil chemotaxis are novel, and
      they expand our understanding of the mechanisms by which these virulence traits
      contribute to the pathogenesis of gram-negative pneumonia and other
      extraintestinal infections.

PMID- 14573666
TI  - Type 1 fimbriae of Salmonella enterica serovar Typhimurium bind to enterocytes
      and contribute to colonization of swine in vivo.
AB  - Salmonella enterica serovar Typhimurium strain 798 is a clinical isolate from a
      pig and is known to be able to cause persistent, asymptomatic infections. This
      strain also is known to exist in two phenotypes (adhesive and nonadhesive to
      enterocytes) and can switch between the two phenotypes at a rate consistent with
      phase variation. Cells in the adhesive phenotype are more readily phagocytosed by
      leukocytes than nonadhesive cells. Once in a leukocyte, adhesive-phase cells
      survive while nonadhesive-phase cells die. In the present study, nonadhesive
      mutants were obtained with the transposon TnphoA. A nonadhesive mutant was
      selected for study and was shown by electron microscopy not to produce fimbriae.
      The gene encoding the adhesin was cloned and sequenced. Based on its sequence,
      the adhesin was shown to be FimA, the major subunit of type 1 fimbriae. The
      nonadhesive mutant was attenuated in its ability to colonize both mouse and pig
      intestines, but remained capable of systemic spread in mice. The nonadhesive
      mutant was phagocytosed to the same extent as parental cells in the adhesive
      phase and then survived intracellularly. These results demonstrated that type 1
      fimbriae were important for attachment to enterocytes and promoted intestinal
      colonization. However, they were not important in promoting phagocytosis or
      intracellular survival.

PMID- 14573667
TI  - Modulation of T-cell costimulation as immunotherapy or immunochemotherapy in
      experimental visceral leishmaniasis.
AB  - CD40 ligand (CD40L)-deficient C57BL/6 mice failed to control intracellular
      Leishmania donovani visceral infection, indicating that acquired resistance
      involves CD40-CD40L signaling and costimulation. Conversely, in wild-type C57BL/6
      and BALB/c mice with established visceral infection, injection of agonist anti
      CD40 monoclonal antibody (MAb) induced killing of approximately 60% of parasites
      within liver macrophages, stimulated gamma interferon (IFN-gamma) secretion, and
      enhanced mononuclear cell recruitment and tissue granuloma formation. Comparable
      parasite killing was also induced by MAb blockade (inhibition) of cytotoxic T
      lymphocyte antigen-4 (CTLA-4) which downregulates separate CD28-B7 T-cell
      costimulation. Optimal killing triggered by both anti-CD40 and anti-CTLA-4
      required endogenous IFN-gamma and involved interleukin 12. CD40L(-/-) mice also
      failed to respond to antileishmanial chemotherapy (antimony), while in normal
      animals, anti-CD40 and anti-CTLA-4 synergistically enhanced antimony-associated
      killing. CD40L-CD40 signaling regulates outcome and response to treatment of
      experimental visceral leishmaniasis, and MAb targeting of T-cell costimulatory
      pathways (CD40L-CD40 and CD28-B7) yields macrophage activation and
      immunotherapeutic and immunochemotherapeutic activity.

PMID- 14573668
TI  - Lung epithelial cells and extracellular matrix components induce expression of
      Pneumocystis carinii STE20, a gene complementing the mating and pseudohyphal
      growth defects of STE20 mutant yeast.
AB  - Pneumocystis carinii causes severe pneumonia in immunocompromised hosts. The
      binding of P. carinii to alveolar epithelial cells and extracellular matrix
      constituents such as fibronectin and vitronectin is a central feature of
      infection, which initiates proliferation of the organism. Herein, we demonstrate
      that P. carinii binding to lung cells specifically alters the gene expression of
      the organism, regulating fungal growth. Subtractive hybridization was performed
      to isolate P. carinii genes expressed following binding to mammalian
      extracellular matrix constituents. P. carinii STE20 (PCSTE20), a gene
      participating in mating and pseudohyphal growth of other fungi, was identified
      following adherence to the extracellular matrix constituents fibronectin,
      vitronectin, collagen, and lung epithelial cells. The expression of PCSTE20 and a
      related P. carinii mitogen-activated protein kinase (MAPK) kinase gene, also
      implicated in signaling of mating, were both specifically upregulated by binding
      to matrix protein. The expression of general cyclin-dependent kinases and other
      MAPKs not involved in mating pathways were not altered by organism binding.
      PCSTE20 expression was also strongly enhanced following organism attachment to
      A549 lung epithelial cells. When expressed in a Saccharomyces cerevisiae
      ste20Delta mutant, PCSTE20 suppressed defects in both mating and pseudohyphal
      growth. These findings are consistent with the observed proliferation and
      filopodial extension of Pneumocystis organisms adherent to the epithelium in the
      lungs of immunocompromised hosts. PCSTE20 expression appears to represent a
      significant component in the regulation of the life cycle of this intractable
      opportunistic pathogen.

PMID- 14573669
TI  - Human phagocytic cell responses to Scedosporium apiospermum (Pseudallescheria
      boydii): variable susceptibility to oxidative injury.
AB  - Scedosporium apiospermum (Pseudallescheria boydii) is an emerging opportunistic
      filamentous fungus that causes serious infections in both immunocompetent and
      immunocompromised patients. To gain insight into the immunopathogenesis of
      infections due to S. apiospermum, the antifungal activities of human
      polymorphonuclear leukocytes (PMNs), mononuclear leukocytes (MNCs), and monocyte
      derived macrophages (MDMs) against two clinical isolates of S. apiospermum were
      evaluated. Isolate SA54A was amphotericin B resistant and was the cause of a
      fatal disseminated infection. Isolate SA1216 (cultured from a successfully
      treated localized subcutaneous infection) was susceptible to amphotericin B. MDMs
      exhibited similar phagocytic activities against conidia of both isolates.
      However, PMNs and MNCs responded differently to the hyphae of these two isolates.
      Serum opsonization of hyphae resulted in a higher level of superoxide anion
      (O(2)(-)) release by PMNs in response to SA54A (amphotericin B resistant) than
      that seen in response to SA1216 (amphotericin B susceptible; P < 0.001). Despite
      this increased O(2)(-) production, PMNs and MNCs induced less hyphal damage to
      SA54A than to SA1216 (P < 0.001). To investigate the potential mechanisms
      responsible for these differences, hyphal damage was evaluated in the presence of
      antifungal oxidative metabolites as well as in the presence of a series of
      inhibitors and scavengers of antifungal PMN function. Mannose, catalase,
      superoxide dismutase, dimethyl sulfoxide, and heparin had no effect on PMN
      induced hyphal damage to either of the two isolates. However, azide, which
      inhibits PMN myeloperoxidase activity, significantly reduced hyphal damage to
      SA1216 (P < 0.01) but not to SA54A. Hyphae of SA1216 were slightly more
      susceptible to oxidative pathway products, particularly HOCl, than those of
      SA54A. Thus, S. apiospermum is susceptible to antifungal phagocytic function to
      various degrees. The selective inhibitory pattern of azide with respect to hyphal
      damage and the parallel susceptibility to HOCl suggests an important difference
      in susceptibilities to myeloperoxidase products that may be related to the
      various levels of pathogenicity and amphotericin B resistance of S. apiospermum.

PMID- 14573670
TI  - Enhanced expression of interleukin-1alpha and tumor necrosis factor receptor
      associated protein 1 in ileal tissues of cattle infected with Mycobacterium avium
      subsp. paratuberculosis.
AB  - Infection with Mycobacterium avium subsp. paratuberculosis is associated with
      high levels of morbidity, decreased production, and early culling in dairy
      cattle. Clinical symptoms of Johne's disease include persistent diarrhea,
      inappetence, and resultant weight loss due to chronic inflammation of the small
      intestine. Although the presence or absence of intestinal lesions cannot be used
      as a definitive indicator of M. avium subsp. paratuberculosis infection, most
      infected cattle exhibit significant changes to intestinal mucosa, with the focus
      of pathology surrounding the ileal cecal junction. Typical pathology of M. avium
      subsp. paratuberculosis infection includes inflammation, thickening of the
      lumenal wall, and hyperplasia in draining lymph nodes. To further understand the
      pathology of Johne's disease, we compared the gene expression profiles of ileal
      tissues from Johne's disease-positive (n = 6), and Johne's disease-negative (n =
      5) Holstein cattle. Gene expression profiles were compared with a bovine total
      leukocyte (BOTL-3) cDNA microarray. Genes that were expressed at significantly
      higher levels (>1.5-fold; P < 0.05) in tissues from Johne's disease-infected
      animals relative to noninfected animals included those encoding tumor necrosis
      factor receptor-associated protein 1 (TRAF1), interleukin-1alpha (IL-1alpha), MCP
      2, N-cadherin, and beta1 integrin (CD29). Dramatic upregulation of IL-1alpha
      (21.5-fold) and TRAF1 (27.5-fold) gene expression in tissues of Johne's disease
      positive cows relative to tissues from control cows was confirmed by quantitative
      real-time PCR. Western blot analysis confirmed that IL-1alpha and TRAF1 mRNA
      levels resulted in increased protein expression in tissues of Johne's disease
      positive cattle relative to tissues from control cattle. High levels of IL-1alpha
      can produce symptoms similar to those found in clinical Johne's disease. Taken
      together, the data presented in this report suggest that many outward symptoms of
      Johne's disease may be due to IL-1alpha toxicity. In addition, enhanced levels of
      TRAF1 could result in cells within the lesions of Johne's disease-positive cattle
      that are highly resistant to TNF-alpha-induced signaling.

PMID- 14573671
TI  - Evidence for a novel gene expression program in peripheral blood mononuclear
      cells from Mycobacterium avium subsp. paratuberculosis-infected cattle.
AB  - A bovine-specific cDNA microarray system was used to compare gene expression
      profiles of peripheral blood mononuclear cells (PBMCs) from control uninfected (n
      = 4) and Johne's disease-positive (n = 6) Holstein cows. Microarray experiments
      were designed so that for each animal, a direct comparison was made between PBMCs
      stimulated in vitro with Mycobacterium avium subsp. paratuberculosis and PBMCs
      stimulated with phosphate-buffered saline (nil-stimulated PBMCs). As expected, M.
      avium subsp. paratuberculosis stimulation of infected cow PBMCs enhanced
      expression of gamma interferon transcripts. In addition, expression of 15 other
      genes was significantly affected (>1.25-fold change; P < 0.05) by in vitro
      stimulation with M. avium subsp. paratuberculosis. Similar treatment of control
      cow PBMCs with M. avium subsp. paratuberculosis resulted in significant changes
      in expression of 13 genes, only 2 of which were also affected in PBMCs from the
      infected cow PBMCs. To compare gene expression patterns in the two cow infection
      groups (infected cows and uninfected cows), a mixed-model analysis was performed
      with the microarray data. This analysis indicated that there were major
      differences in the gene expression patterns between cells isolated from the two
      groups of cows, regardless of in vitro stimulation. A total of 86 genes were
      significantly differentially expressed (P < 0.01) in M. avium subsp.
      paratuberculosis-stimulated PBMCs from infected cows compared to expression in
      similarly treated PBMCs from control cows. Surprisingly, a larger number of genes
      (110 genes) were also found to be significantly differentially expressed (P <
      0.01) in nil-stimulated cells from the two infection groups. The expression
      patterns of selected genes were substantiated by quantitative real-time reverse
      transcriptase PCR. Flow cytometric analysis indicated that there were no gross
      differences in the relative populations of major immune cell types in PBMCs from
      infected and control cows. Thus, data presented in this report indicate that the
      gene expression program of PBMCs from M. avium subsp. paratuberculosis-infected
      cows is inherently different from that of cells from control uninfected cows.

PMID- 14573672
TI  - Recombinant Leishmania major secreting biologically active granulocyte-macrophage
      colony-stimulating factor survives poorly in macrophages in vitro and delays
      disease development in mice.
AB  - Leishmania is an intracellular pathogen that replicates inside macrophages.
      Activated macrophages produce a specific subset of cytokines that play an
      important role in the control of Leishmania infections. As part of our interest
      in developing suicide parasites that produce abortive infections for the purposes
      of vaccination, we engineered recombinant Leishmania major strains producing
      biologically active granulocyte-macrophage colony-stimulating factor (GM-CSF). We
      showed that GM-CSF is being produced in the phagosomes of infected macrophages
      and that it can be detected in the culture supernatants of both infected
      macrophages and extracellular parasites. Our data support the notion that GM-CSF
      secreted by both developmental forms of recombinant L. major can activate
      macrophages to produce high levels of proinflammatory cytokines such as
      interleukin-1beta (IL-1beta), IL-6, and IL-18 and various chemokines including
      RANTES/CCL5, MIP-1alpha/CCL3, MIP-1beta/CCL4, MIP-2/CXCL2, and MCP-1/CCL2, which
      enhance parasite killing. Indeed, GM-CSF-expressing parasites survive poorly in
      macrophages in vitro and produce delayed lesion development in susceptible BALB/c
      mice in vivo. Selective killing of intracellular Leishmania expressing cytokine
      genes capable of activating cellular responses may constitute a promising
      strategy to control and/or prevent parasitic infections.

PMID- 14573673
TI  - Growth phase-dependent response of Helicobacter pylori to iron starvation.
AB  - Iron is an essential nutrient that is often found in extremely limited available
      quantities within eukaryotic hosts. Because of this, many pathogenic bacteria
      have developed regulated networks of genes important for iron uptake and storage.
      In addition, it has been shown that many bacteria use available iron
      concentrations as a signal to regulate virulence gene expression. We have
      utilized DNA microarray technology to identify genes of the human pathogen
      Helicobacter pylori that are differentially regulated on a growth-inhibiting
      shift to iron starvation conditions. In addition, the growth phase-dependent
      expression of these genes was investigated by examining both exponential and
      stationary growth phase cultures. We identified known iron-regulated genes, as
      well as a number of genes whose regulation by iron concentration was not
      previously appreciated. Included in the list of regulated factors were the known
      virulence genes cagA, vacA, and napA. We examined the effect of iron starvation
      on the motility of H. pylori and found that exponential- and stationary-phase
      cultures responded differently to the stress. We further found that while growing
      cells are rapidly killed by iron starvation, stationary-phase cells show a
      remarkable ability to survive iron depletion. Finally, bioinformatic analysis of
      the predicted promoter regions of the differentially regulated genes led to
      identification of several putative Fur boxes, suggesting a direct role for Fur in
      iron-dependent regulation of these genes.

PMID- 14573674
TI  - Comparative pathogenicity of Escherichia coli O157 and intimin-negative non-O157
      Shiga toxin-producing E coli strains in neonatal pigs.
AB  - We compared the pathogenicity of intimin-negative non-O157:H7 Shiga toxin (Stx)
      producing Escherichia coli (STEC) O91:H21 and O104:H21 strains with the
      pathogenicity of intimin-positive O157:H7 and O157:H(-) strains in neonatal pigs.
      We also examined the role of Stx2d-activatable genes and the large hemolysin
      encoding plasmid of O91:H21 strain B2F1 in the pathogenesis of STEC disease in
      pigs. We found that all E. coli strains that made wild-type levels of Stx caused
      systemic illness and histological lesions in the brain and intestinal crypts,
      whereas none of the control Stx-negative E. coli strains evoked comparable
      central nervous system signs or intestinal lesions. By contrast, the absence of
      intimin, hemolysin, or motility had little impact on the overall pathogenesis of
      systemic disease during STEC infection. The most striking differences between
      pigs inoculated with non-O157 STEC strains and pigs inoculated with O157 STEC
      strains were the absence of attaching and effacing intestinal lesions in pigs
      inoculated with non-O157:H7 strains and the apparent association between the
      level of Stx2d-activatable toxin produced by an STEC strain and the severity of
      lesions.

PMID- 14573676
TI  - Forssman synthetase expression results in diminished shiga toxin susceptibility:
      a role for glycolipids in determining host-microbe interactions.
AB  - Forssman glycolipid (FG), the product of Forssman synthetase (FS), is widely
      expressed among nonprimate mammalian species. Here, we describe a molecular and
      genetic relationship between FG expression and Shiga toxin (Stx) susceptibility.
      We have isolated the FS cDNA from human, canine, and murine cells. Whereas the
      murine and canine FS genes express a functional enzyme, the human FS cDNA was
      found to express a protein that lacks FS activity, despite a high degree of
      sequence identity with the enzymatically active murine and canine FS genes. In
      order to examine the relationship between FG expression and Stx susceptibility,
      Vero cells were transfected with the three FS orthologues or a vector control.
      Complementation with the human FS cDNA had no effect on Stx susceptibility,
      whereas stable expression of the canine and murine FS resulted in markedly
      decreased susceptibility to toxin. Among individual cells, an inverse correlation
      between FG expression and Stx binding was demonstrated. Moreover, only strongly
      FG-reactive cells were capable of growing in the presence of Stx. These cells
      were found to have high levels of FG expression and a correspondingly diminished
      GbO(3) content. We conclude that expression of a functionally active FS modifies
      Stx receptor glycolipids to FG and results in markedly decreased susceptibility
      to toxin. We speculate that inactivation of the FS gene during primate evolution
      may account, at least in part, for the marked susceptibility of human cells to
      Stx.

PMID- 14573675
TI  - Characterization of gp70 and anti-gp70 monoclonal antibodies in Paracoccidioides
      brasiliensis pathogenesis.
AB  - Paracoccidioidomycosis (PCM) is a systemic granulomatous mycosis whose agent is
      Paracoccidioides brasiliensis. In the culture supernatant, the fungus expresses
      glycoproteins of from 13 to 148 kDa. A cell surface glycoprotein of 43 kDa is the
      major antigenic component of P. brasiliensis. Another expressed glycoprotein,
      gp70, is recognized by 96% of sera from PCM patients and is able to induce
      lymphoproliferation. Since, little is known about this glycoprotein, we produced
      monoclonal antibodies (MAbs) against gp70 to isolate the molecule from total
      fungus extracts and to investigate its possible role in the pathogenesis of PCM.
      Using these MAbs, it was observed by confocal microscopy that gp70 is located
      mainly in the intracellular compartment of the fungus, although it was also
      detected in the culture supernatant. Based on observations showing that gp43 has
      a down-regulatory effect on mouse peritoneal macrophages, we tested the effects
      of gp70 on their phagocytic ability. Purified gp70 was able to inhibit the
      activity of macrophages through the mannose receptors and also through the Fc
      receptors; the latter effect was not observed with gp43. gp70 inhibits NO and
      H(2)O(2) liberation by peritoneal macrophages in vitro, as does gp43. Results
      obtained with gp43 led us to hypothesize that gp70 could act as an escape
      mechanism for fungal establishment in primary infections. To corroborate this
      hypothesis, we analyzed the effect of passive immunization of mice during
      infection with P. brasiliensis using anti-gp70 MAbs. This treatment almost
      completely abolished granuloma formation in the lungs, suggesting that the
      protein facilitates fungal establishment and progression of lesions in primary
      infection.

PMID- 14573677
TI  - Inhibition of platelet adherence to brain microvasculature protects against
      severe Plasmodium berghei malaria.
AB  - Some patients with Plasmodium falciparum infections develop cerebral malaria,
      acute respiratory distress, and shock and ultimately die even though drug therapy
      has eliminated the parasite from the blood, suggesting that a systemic
      inflammatory response contributes to malarial pathogenesis. Plasmodium berghei
      infected mice are a well-recognized model of severe malaria (experimental severe
      malaria [ESM]), and infected mice exhibit a systemic inflammatory response.
      Because platelets are proposed to contribute to ESM and other systemic
      inflammatory responses, we determined whether platelet adherence contributes to
      experimental malarial pathogenesis. Indeed, a significant (P < 0.005) increase in
      the number of rolling and adherent platelets was observed by intravital
      microscopy in brain venules of P. berghei-infected mice compared with the number
      in uninfected controls. P-selectin- or ICAM-1-deficient mice exhibit increased
      survival after P. berghei infection. We observed a significant (P < 0.0001)
      reduction in the morbidity of mice injected with anti-CD41 (alpha(IIb) or gpIIb)
      monoclonal antibody on day 1 of P. berghei infection compared with the morbidity
      of infected controls injected with rat immunoglobulin G. Additionally, platelet
      rolling and adhesion in brain venules were reduced in P. berghei mice lacking
      either P-selectin or ICAM-1 or when the platelets were coated with anti-CD41
      monoclonal antibody. Unlike other inflammatory conditions, we did not detect
      platelet-leukocyte interactions during P. berghei malaria. Because (i). leukocyte
      adhesion is not markedly altered in the absence of P-selectin or ICAM-1 and (ii).
      CD41 is not an adhesion molecule for parasitized erythrocytes, these findings
      support the hypothesis that inhibition of platelet adhesion to the brain
      microvasculature protects against development of malarial pathogenesis.

PMID- 14573678
TI  - The Leishmania infantum acidic ribosomal protein P0 administered as a DNA vaccine
      confers protective immunity to Leishmania major infection in BALB/c mice.
AB  - In this study, we examined the immunogenic properties of the Leishmania infantum
      acidic ribosomal protein P0 (LiP0) in the BALB/c mouse model. The humoral and
      cellular responses induced by the administration of the LiP0 antigen, either as
      soluble recombinant LiP0 (rLiP0) or as a plasmid DNA formulation (pcDNA3-LiP0),
      were determined. Also, the immunological response associated with a prime-boost
      strategy, consisting of immunization with pcDNA3-LiP0 followed by a boost with
      rLiP0, was assayed. Immunization with rLiP0 induced a predominant Th2-like
      humoral response, but no anti-LiP0 antibodies were induced after immunization
      with pcDNA3-LiP0, whereas a strong humoral response consisting of a mixed
      immunoglobulin G2a (IgG2a)-IgG1 isotype profile was induced in mice immunized
      with the prime-boost regime. For all three immunization protocols, rLiP0
      stimulated production of gamma interferon (IFN-gamma) in both splenocytes and
      lymph node cells from immunized mice was observed. However, it was only when mice
      were immunized with pcDNA3-LiP0 that noticeable protection against L. major
      infection was achieved, as determined by both lesion development and parasite
      burden. Immunization of mice with LiP0-DNA primes both CD4(+) and CD8(+) T cells,
      which, with the L. major challenge, were boosted to produce significant levels of
      IL-12-dependent, antigen-specific IFN-gamma. Taken together, these data indicate
      that genetic vaccination with LiP0 induces protective immunological effector
      mechanisms, yet the immunological response elicited by LiP0 is not sufficient to
      keep the infection from progressing.

PMID- 14573679
TI  - Correlation between cag pathogenicity island composition and Helicobacter pylori
      associated gastroduodenal disease.
AB  - Helicobacter pylori infection is associated with a variety of outcomes ranging
      from seemingly asymptomatic coexistence to peptic ulcer disease and gastric
      cancer. The cag pathogenicity island (PAI) contains genes associated with a more
      aggressive phenotype and has been suggested to be a determinant of severe disease
      outcome. The cagA gene has served as a marker for the cag PAI. However, the
      presence of this single gene does not necessarily indicate the presence of a
      complete set of cag PAI genes. We have analyzed the composition of the cag PAI in
      66 clinical isolates obtained from patients with duodenal ulcer, gastric cancer,
      and nonulcer dyspepsia. Hybridization of DNA to microarrays containing all the
      genes of the cag PAI showed that 76 and 9% of the strains contained all or none
      of the cag PAI genes, respectively. Partial deletions of the cag PAI were found
      in 10 isolates (15%), of which 3 were cagA negative. The ability to induce
      interleukin-8 (IL-8) production in AGS cells was correlated to the presence of a
      complete cag PAI. Strains carrying only parts of the island induced IL-8 at
      levels significantly lower than those induced by cag PAI-positive isolates. The
      presence of an intact cag PAI correlates with development of more severe
      pathology, and such strains were found more frequently in patients with severe
      gastroduodenal disease (odds ratio, 5.13; 95% confidence interval, 1.5 to 17.4).
      Partial deletions of the cag PAI appear to be sufficient to render the organism
      less pathogenic.

PMID- 14573680
TI  - CapG(-/-) mice have specific host defense defects that render them more
      susceptible than CapG(+/+) mice to Listeria monocytogenes infection but not to
      Salmonella enterica serovar Typhimurium infection.
AB  - Loss of the actin filament capping protein CapG has no apparent effect on the
      phenotype of mice maintained under sterile conditions; however, bone marrow
      derived macrophages from CapG(-/-) mice exhibited distinct motility defects. We
      examined the ability of CapG(-/-) mice to clear two intracellular bacteria,
      Listeria monocytogenes and Salmonella enterica serovar Typhimurium. The 50%
      lethal dose of Listeria was 10-fold lower for CapG(-/-) mice than for CapG(+/+)
      mice (6 x 10(3) CFU for CapG(-/-) mice and 6 x 10(4) CFU for CapG(+/+) mice),
      while no difference was observed for Salmonella: The numbers of Listeria cells in
      the spleens and livers were significantly higher in CapG(-/-) mice than in
      CapG(+/+) mice at days 5 to 9, while the bacterial counts were identical on day 5
      for Salmonella-infected mice. Microscopic analysis revealed qualitatively similar
      inflammatory responses in the spleens and livers of the two types of mice.
      Specific immunofluorescence staining analyzed by fluorescence-activated cell
      sorting revealed similar numbers of macrophages and dendritic cells in infected
      CapG(-/-) and CapG(+/+) spleens. However, analysis of bone marrow-derived
      macrophages revealed a 50% reduction in the rate of phagocytosis of Listeria in
      CapG(-/-) cells but a normal rate of phagocytosis of Salmonella: Stimulation of
      bone marrow-derived dendritic cells with granulocyte-macrophage colony
      stimulating factor resulted in a reduction in the ruffling response of CapG(-/-)
      cells compared to the response of CapG(+/+) cells, and CapG(-/-) bone-marrowed
      derived neutrophils migrated at a mean speed that was nearly 50% lower than the
      mean speed of CapG(+/+) neutrophils. Our findings suggest that specific motility
      deficits in macrophages, dendritic cells, and neutrophils render CapG(-/-) mice
      more susceptible than CapG(+/+) mice to Listeria infection.

PMID- 14573681
TI  - Phosphatidylcholine-specific phospholipase C and sphingomyelinase activities in
      bacteria of the Bacillus cereus group.
AB  - Bacillus anthracis is nonhemolytic, even though it is closely related to the
      highly hemolytic Bacillus cereus. Hemolysis by B. cereus results largely from the
      action of phosphatidylcholine-specific phospholipase C (PC-PLC) and
      sphingomyelinase (SPH), encoded by the plc and sph genes, respectively. In B.
      cereus, these genes are organized in an operon regulated by the global regulator
      PlcR. B. anthracis contains a highly similar cereolysin operon, but it is
      transcriptionally silent because the B. anthracis PlcR is truncated at the C
      terminus. Here we report the cloning, expression, purification, and enzymatic
      characterization of PC-PLC and SPH from B. cereus and B. anthracis. We also
      investigated the effects of expressing PlcR on the expression of plc and sph. In
      B. cereus, PlcR was found to be a positive regulator of plc but a negative
      regulator of sph. Replacement of the B. cereus plcR gene by its truncated
      orthologue from B. anthracis eliminated the activities of both PC-PLC and SPH,
      whereas introduction into B. anthracis of the B. cereus plcR gene with its own
      promoter did not activate cereolysin expression. Hemolytic activity was detected
      in B. anthracis strains containing the B. cereus plcR gene on a multicopy plasmid
      under control of the strong B. anthracis protective antigen gene promoter or in a
      strain carrying a multicopy plasmid containing the entire B. cereus plc-sph
      operon. Slight hemolysis and PC-PLC activation were found when PlcR-producing B.
      anthracis strains were grown under anaerobic-plus-CO(2) or especially under
      aerobic-plus-CO(2) conditions. Unmodified parental B. anthracis strains did not
      demonstrate obvious hemolysis under the same conditions.

PMID- 14573682
TI  - Role of actin filament network in Burkholderia multivorans invasion in well
      differentiated human airway epithelia.
AB  - The role of the actin-based cytoskeleton in the internalization process of
      Burkholderia multivorans by well-differentiated human airway epithelia was
      investigated by immunohistology and confocal microscopy. Our data suggest that an
      intact actin cytoskeleton is required for biofilm formation but not single cell
      entry or paracytosis.

PMID- 14573683
TI  - Commensal bacteria increase invasion of intestinal epithelium by Salmonella
      enterica serovar Typhi.
AB  - The intestinal microflora consists of a heterogeneous population of
      microorganisms and has many effects on the health status of its human host. Here,
      it is shown that the products of certain strains of bacteria normally present in
      the intestinal microflora are able to trigger redistribution of the cystic
      fibrosis transmembrane conductance regulator (CFTR) protein in epithelial cells.
      CFTR is used by Salmonella enterica serovar Typhi as a receptor on epithelial
      cells which mediate the translocation of this microorganism to the gastric
      submucosa. Serovar Typhi-epithelial cell adhesion and CFTR-dependent invasion by
      serovar Typhi of epithelial cells were increased following commensal-mediated
      CFTR redistribution. These data suggest that commensal microorganisms present in
      the intestinal lumen can affect the efficiency of serovar Typhi invasion of the
      intestinal submucosa. This could be a key factor influencing host susceptibility
      to typhoid fever.

PMID- 14573684
TI  - Vaccination with Toxoplasma gondii SAG-1 protein is protective against congenital
      toxoplasmosis in BALB/c mice but not in CBA/J mice.
AB  - We evaluated the effect of vaccination with the SAG1 protein of Toxoplasma gondii
      against congenital toxoplasmosis in mice with different genetic backgrounds. In
      BALB/c mice (H-2(d)), vaccination reduced the number of infected fetuses by 50%
      and was associated with a mixed type 1 and type 2 immunity. In CBA/J mice (H
      2(k)), vaccination increased the number of infected fetuses by 50% and was
      associated with a predominant type 2 response. Our results indicate that the
      effect of vaccination with SAG1 is controlled by the genetic background of the
      mouse.

PMID- 14573685
TI  - Antibodies that inhibit Plasmodium falciparum adhesion to chondroitin sulfate A
      are associated with increased birth weight and the gestational age of newborns.
AB  - Antibodies that inhibit Plasmodium falciparum adhesion to the placental receptor
      chondroitin sulfate A are associated with a reduced risk of placental malaria,
      but whether these antibodies lead to improved pregnancy outcomes is unknown. We
      measured antiadhesion antibody levels in parturient women in western Kenya, where
      malaria transmission is intense. Secundigravid women with antiadhesion activity
      in their plasma delivered babies that were on average 398 g heavier (P = 0.019)
      and 2 weeks more mature (P = 0.002) than babies delivered to secundigravidas
      without antiadhesion activity. Our findings support the development of
      antiadhesion vaccines to prevent poor fetal outcomes due to pregnancy malaria.

PMID- 14573686
TI  - Detection of N-(3-oxohexanoyl)-L-homoserine lactone in mice infected with
      Yersinia enterocolitica serotype O8.
AB  - Yersinia enterocolitica synthesizes N-acyl-L-homoserine lactone (AHL) signal
      molecules via the LuxR-LuxI homologues YenR-YenI. In this study we checked two
      prototypes of mouse-virulent Y. enterocolitica serotype O8 strains WA-314 and
      8081 for AHL production in vitro and in vivo (mouse infection model). We used
      thin-layer chromatography in combination with the Escherichia coli AHL biosensor
      to identify the AHL species produced. We detected only OHHL [N-(3-oxohexanoyl)-L
      homoserine lactone] and not HHL (N-hexanoyl-L-homoserine lactone) produced by Y.
      enterocolitica O8 in culture supernatant or infected mouse tissue. This is the
      first report demonstrating AHL production by yersiniae during infection.

PMID- 14573687
TI  - Simultaneous variation of the immunodominant outer membrane proteins, MSP2 and
      MSP3, during anaplasma marginale persistence in vivo.
AB  - Vector-borne bacterial pathogens persist in the mammalian host by varying surface
      antigens to evade the existing immune response. To test whether the model of
      surface coat switching and immune evasion can be extended to a vector-borne
      bacterial pathogen with multiple immunodominant surface proteins, we examined
      Anaplasma marginale, a rickettsia with two highly immunogenic outer membrane
      proteins, major surface protein 2 (MSP2) and MSP3. The simultaneous clearance of
      variants of the two most immunodominant surface proteins of A. marginale followed
      by emergence of unique variants indicates that the switch rates and immune
      selection for MSP2 and MSP3 are sufficiently similar to explain the cyclic
      bacteremia observed during infection in the immunocompetent host.

PMID- 14573688
TI  - A CdtA-CdtC complex can block killing of HeLa cells by Haemophilus ducreyi
      cytolethal distending toxin.
AB  - The cytolethal distending toxin (CDT) of Haemophilus ducreyi is comprised of the
      CdtA, CdtB, and CdtC proteins, with the CdtB protein having demonstrated
      enzymatic (i.e., DNase) activity. Using a single recombinant Escherichia coli
      strain with two plasmids individually containing the H. ducreyi cdtA and cdtC
      genes, we purified a noncovalent CdtA-CdtC complex. Incubation of this CdtA-CdtC
      complex with HeLa cells blocked killing of these cells by CDT holotoxin.
      Furthermore, the addition of purified recombinant CdtB to HeLa cells preincubated
      with the CdtA-CdtC complex resulted in the killing of these human epithelial
      cells.

PMID- 14573689
TI  - Mice deficient in nuclear factor of activated T-cell transcription factor c2
      mount increased Th2 responses after infection with Nippostrongylus brasiliensis
      and decreased Th1 responses after mycobacterial infection.
AB  - Infection of nuclear factor of activated T-cell transcription factor c2 (NFATc2)
      deficient mice with the helminth Nippostrongylus brasiliensis led to a distinct
      increase in interleukin-4 (IL-4) and IL-5 protein synthesis by lymph node and
      spleen cells and to elevated serum immunoglobulin E (IgE) levels in comparison to
      those seen with infected control mice. While IL-4, IL-5, and IL-13 mRNA
      expression was also enhanced in lymph node cells from the lungs of infected
      NFATc2(-/-) mice, the number of T cells secreting Th2-type lymphokines remained
      the same in mice infected with N. brasiliensis. In contrast, lymphocytes from
      NFATc2-deficient mice infected with Mycobacterium bovis BCG secreted less gamma
      interferon than lymphocytes from infected control mice. These findings indicate
      that NFATc2 is an activator of Th1 responses and a suppressor of Th2 responses in
      vivo.

PMID- 14573690
TI  - Novel role for albumin in innate immunity: serum albumin inhibits the growth of
      Blastomyces dermatitidis yeast form in vitro.
AB  - In this study we found that serum inhibitory activity against Blastomyces
      dermatitidis was principally mediated by albumin. This was confirmed in
      experiments using albumin from several mammalian species. Analbuminemic rat serum
      did not inhibit B. dermatitidis growth in vivo; however, the addition of albumin
      restored inhibitory activity. Inhibitory activity does not require albumin domain
      III and appears to involve binding of a low-molecular-weight yeast-derived growth
      factor.

PMID- 14573691
TI  - Toll-like receptor expression in C3H/HeN and C3H/HeJ mice during Salmonella
      enterica serovar Typhimurium infection.
AB  - Here, we have investigated the mRNA expression of Toll-like receptor 2 (TLR-2),
      TLR-4, and MD-2 in spleens and livers of C3H/HeN mice (carrying wild-type TLR-4)
      and C3H/HeJ mice (carrying mutated TLR-4) in response to Salmonella infection.
      During Salmonella infections, TLR-4 is activated, leading to increased TLR-2 and
      decreased TLR-4 expression.

PMID- 14573692
TI  - Differences in host susceptibility to disease progression in the human challenge
      model of Haemophilus ducreyi infection.
AB  - With human volunteers inoculated at two sites with Haemophilus ducreyi, outcomes
      for a subject were not independent. In a reinfection trial, 2 of 11 previous
      pustule formers and 6 of 10 previous resolvers resolved all sites of infection.
      There was no correlation between serum bactericidal or phagocytic activity and
      outcome in the trial. These data indicate that different hosts are differentially
      susceptible to disease progression versus resolution in the model.

PMID- 14573693
TI  - Helicobacter pylori cag pathogenicity island is associated with reduced
      expression of interleukin-4 (IL-4) mRNA and modulation of the IL-4delta2 mRNA
      isoform in human gastric mucosa.
AB  - Interleukin-4 (IL-4) and IL-4delta2 mRNA gastric expression was evaluated in
      healthy subjects and patients who did not have ulcers but were infected with
      Helicobacter pylori with or without the cag pathogenicity island (cag PAI). IL-4
      mRNA was physiologically expressed by gastric epithelium and negatively
      influenced by H. pylori. Also, nonepithelial cells in the lamina propria of H.
      pylori-infected patients expressed IL-4 mRNA, whereas IL-4delta2 mRNA was found
      only in cag PAI-negative patients. Thus, gastric IL-4 takes part in the local
      immune response to H. pylori.

PMID- 14573694
TI  - Increased density of human immunodeficiency virus type 1 coreceptors CCR5 and
      CXCR4 on the surfaces of CD4(+) T cells and monocytes of patients with
      Schistosoma mansoni infection.
AB  - Distribution of chemokine receptors CCR5 and CXCR4, which are also coreceptors
      for human immunodeficiency virus type 1 invasion of cells, was measured on the
      surfaces of CD4(+) T cells and monocytes in peripheral blood samples from a group
      of Kenyan car washers. Patients with active schistosomiasis displayed higher cell
      surface densities of these receptors than did cured schistosomiasis patients.

PMID- 14573695
TI  - Legionella pneumophila suppresses macrophage interleukin-12 production by
      activating the p42/44 mitogen-activated protein kinase cascade.
AB  - A possible involvement of the mitogen-activated protein (MAP) kinase cascade in
      the inhibition of macrophage interleukin-12 (IL-12) production by Legionella
      pneumophila infection was examined. The results of MAP kinase inhibition by
      p42/44 and p38 MAP kinase inhibitors and of p42/44 MAP kinase activity assays
      indicate that L. pneumophila infection of macrophages causes a selective
      inhibition of lipopolysaccharide-induced IL-12 production by activating the
      p42/44 MAP kinase cascade. In addition, it was also revealed that the p38 MAP
      kinase may be important for the production of IL-12 but not for the inhibition
      caused by L. pneumophila infection.

PMID- 14573696
TI  - The MicAB two-component signaling system is involved in virulence of
      Streptococcus pneumoniae.
AB  - In Streptococcus pneumoniae, the two-component signaling system MicAB was
      previously shown to contribute to repression of competence when oxygen is
      limited. In virulent strains expressing the serotype 2 and 6 capsule, mutation of
      the MicB kinase reduced the lag period of growth when cultures were switched from
      an aerobic to anaerobic atmosphere. After intranasal challenge of mice, the
      micB::km mutation decreased virulence, as shown by the absence of symptoms and by
      a lower level of recovery of CFU from lungs and blood. It is proposed that MicAB
      is involved in the adaptive response of the bacteria to changes in oxygen level
      during the course of infection.

PMID- 14573698
TI  - Humoral immunity against Bordetella pertussis: antibodies or B cells?

PMID- 14573697
TI  - Secretion of the orgC gene product by Salmonella enterica serovar Typhimurium.
AB  - HilA activates the transcription of genes on Salmonella pathogenicity island 1
      (SPI1), which encodes a type III secretion system (TTSS). Previous studies showed
      that transposon insertions in orgC, a gene located on SPI1, increase hilA
      expression. We characterize the orgC gene product and show that it is secreted
      via the SPI1 TTSS. We propose a model whereby OrgC functions as a secreted
      repressor of the SPI1 virulence genes.

PMID- 14573699
TI  - Dynamics of the interaction between a fibronectin molecule and a living bacterium
      under mechanical force.
AB  - Fibronectin (Fn) is an important mediator of bacterial invasions and of
      persistent infections like that of Staphylococcus epidermis. Similar to many
      other types of cell-protein adhesion, the binding between Fn and S. epidermidis
      takes place under physiological shear rates. We investigated the dynamics of the
      interaction between individual living S. epidermidis cells and single Fn
      molecules under mechanical force by using the scanning force microscope. The
      mechanical strength of this interaction and the binding site in the Fn molecule
      were determined. The energy landscape of the binding/unbinding process was
      mapped, and the force spectrum and the association and dissociation rate
      constants of the binding pair were measured. The interaction between S.
      epidermidis cells and Fn molecules is compared with those of two other
      protein/ligand pairs known to mediate different dynamic states of adhesion of
      cells under a hydrodynamic flow: the firm adhesion mediated by biotin/avidin
      interactions, and the rolling adhesion, mediated by L-selectin/P-selectin
      glycoprotein ligand-1 interactions. The inner barrier in the energy landscape of
      the Fn case characterizes a high-energy binding mode that can sustain larger
      deformations and for significantly longer times than the correspondent high
      strength L-selectin/P-selectin glycoprotein ligand-1 binding mode. The
      association kinetics of the former interaction is much slower to settle than the
      latter. On this basis, the observations made at the macroscopic scale by other
      authors of a strong lability of the bacterial adhesions mediated by Fn under high
      turbulent flow are rationalized at the molecular level.

PMID- 14573700
TI  - Identification of functional similarities between proteins using directed
      evolution.
AB  - Protein sequences are often highly redundant and evolution can change them beyond
      recognition. It can therefore be difficult to identify proteins with functional
      or structural similarities by inspection of their sequences. Here we have used an
      experimental evolutionary approach to detect hidden similarities between the
      antisense RNA-binding protein Rop and other proteins. We created an envelope of
      functional Rop mutants by combinatorial mutagenesis, used the compilation of
      mutant sequences to search a database of protein structures, and thereby
      identified a segment of the enzyme valyl-tRNA-synthetase (ValRS). Further
      inspection revealed that the structures of the RNA-binding sites of both proteins
      are highly related, as indeed are the RNA ligands. From the known 3D structure of
      the ValRS in complex with tRNA, we were able to build a model of an RNA hairpin
      pair in complex with Rop that has proved to be consistent with the biochemical
      and NMR data for the interaction between Rop and RNA hairpins. We suggest that
      this approach (mutational envelope scanning), by generating sequence information
      de novo, can help uncover hidden similarities between proteins.

PMID- 14573701
TI  - Differential effects on bone of estrogen receptor alpha and androgen receptor
      activation in orchidectomized adult male mice.
AB  - Androgens may regulate the male skeleton either directly by stimulation of the
      androgen receptor (AR) or indirectly by aromatization of androgens into estrogens
      and, thereafter, by stimulation of the estrogen receptors (ERs). To directly
      compare the effect of ER activation on bone in vivo with the effect of AR
      activation, 9-month-old orchidectomized wild-type and ER-inactivated mice were
      treated with the nonaromatizable androgen 5alpha-dihydrotestosterone, 17beta
      estradiol, or vehicle. Both ERalpha and AR but not ERbeta activation preserved
      the amount of trabecular bone. ERalpha activation resulted both in a preserved
      thickness and number of trabeculae. In contrast, AR activation exclusively
      preserved the number of trabeculae, whereas the thickness of the trabeculae was
      unaffected. Furthermore, the effects of 17beta-estradiol could not be mediated by
      the AR, and the effects of 5alpha-dihydrotestosterone were increased rather than
      decreased in ER-inactivated mice. ERalpha, but not AR or ERbeta, activation
      resulted in preserved thickness, volumetric density, and mechanical strength of
      the cortical bone. ERalpha activation increased serum levels of insulin-like
      growth factor I, which were positively correlated with all the cortical and
      trabecular bone parameters that were specifically preserved by ERalpha activation
      but not by AR activation, suggesting that insulin-like growth factor I might
      mediate these effects of ERalpha activation. Thus, the in vivo bone-sparing
      effect of ERalpha activation is distinct from the bone-sparing effect of AR
      activation in adult male mice. Because these two pathways are clearly distinct
      from each other, one may speculate that a combined treatment of selective ER
      modulators and selective AR modulators might be beneficial in the treatment of
      osteoporosis.

PMID- 14573702
TI  - Botulinum toxin type B micromechanosensor.
AB  - Botulinum neurotoxin (BoNT) types A, B, E, and F are toxic to humans; early and
      rapid detection is essential for adequate medical treatment. Presently available
      tests for detection of BoNTs, although sensitive, require hours to days. We
      report a BoNT-B sensor whose properties allow detection of BoNT-B within minutes.
      The technique relies on the detection of an agarose bead detachment from the tip
      of a micromachined cantilever resulting from BoNT-B action on its substratum, the
      synaptic protein synaptobrevin 2, attached to the beads. The mechanical resonance
      frequency of the cantilever is monitored for the detection. To suspend the bead
      off the cantilever we use synaptobrevin's molecular interaction with another
      synaptic protein, syntaxin 1A, that was deposited onto the cantilever tip.
      Additionally, this bead detachment technique is general and can be used in any
      displacement reaction, such as in receptor-ligand pairs, where the introduction
      of one chemical leads to the displacement of another. The technique is of broad
      interest and will find uses outside toxicology.

PMID- 14573703
TI  - Protein profiles associated with survival in lung adenocarcinoma.
AB  - Morphologic assessment of lung tumors is informative but insufficient to
      adequately predict patient outcome. We previously identified transcriptional
      profiles that predict patient survival, and here we identify proteins associated
      with patient survival in lung adenocarcinoma. A total of 682 individual protein
      spots were quantified in 90 lung adenocarcinomas by using quantitative two
      dimensional polyacrylamide gel electrophoresis analysis. A leave-one-out cross
      validation procedure using the top 20 survival-associated proteins identified by
      Cox modeling indicated that protein profiles as a whole can predict survival in
      stage I tumor patients (P = 0.01). Thirty-three of 46 survival-associated
      proteins were identified by using mass spectrometry. Expression of 12 candidate
      proteins was confirmed as tumor-derived with immunohistochemical analysis and
      tissue microarrays. Oligonucleotide microarray results from both the same tumors
      and from an independent study showed mRNAs associated with survival for 11 of 27
      encoded genes. Combined analysis of protein and mRNA data revealed 11 components
      of the glycolysis pathway as associated with poor survival. Among these
      candidates, phosphoglycerate kinase 1 was associated with survival in the protein
      study, in both mRNA studies and in an independent validation set of 117
      adenocarcinomas and squamous lung tumors using tissue microarrays. Elevated
      levels of phosphoglycerate kinase 1 in the serum were also significantly
      correlated with poor outcome in a validation set of 107 patients with lung
      adenocarcinomas using ELISA analysis. These studies identify new prognostic
      biomarkers and indicate that protein expression profiles can predict the outcome
      of patients with early-stage lung cancer.

PMID- 14573704
TI  - PA-457: a potent HIV inhibitor that disrupts core condensation by targeting a
      late step in Gag processing.
AB  - New HIV therapies are urgently needed to address the growing problem of drug
      resistance. In this article, we characterize the anti-HIV drug candidate 3-O
      (3',3'-dimethylsuccinyl) betulinic acid (PA-457). We show that PA-457 potently
      inhibits replication of both WT and drug-resistant HIV-1 isolates and demonstrate
      that the compound acts by disrupting a late step in Gag processing involving
      conversion of the capsid precursor (p25) to mature capsid protein (p24). We find
      that virions from PA-457-treated cultures are noninfectious and exhibit an
      aberrant particle morphology characterized by a spherical, acentric core and a
      crescent-shaped, electron-dense shell lying just inside the viral membrane. To
      identify the determinants of compound activity we selected for PA-457-resistant
      virus in vitro. Consistent with the effect on Gag processing, we found that
      mutations conferring resistance to PA-457 map to the p25 to p24 cleavage site. PA
      457 represents a unique class of anti-HIV compounds termed maturation inhibitors
      that exploit a previously unidentified viral target, providing additional
      opportunities for HIV drug discovery.

PMID- 14573705
TI  - An experimental platform for studying growth and invasiveness of tumor cells
      within teratomas derived from human embryonic stem cells.
AB  - There is currently no available experimental system wherein human cancer cells
      can be grown in the context of a mixed population of normal differentiated human
      cells for testing biological aspects of cancer cell growth (e.g., tumor cell
      invasion and angiogenesis) or response to anti-cancer therapies. When implanted
      into immunocompromised mice, human embryonic stem cells develop teratomas
      containing complex structures comprising differentiated cell types representing
      the major germ line-derived lineages. We sought to determine whether human cancer
      cells would grow within such teratomas and display properties associated with
      malignancy, such as invasiveness and recruitment of blood vessels. HEY ovarian
      cancer cells stably expressing an H2A-GFP fusion protein (HEY-GFP) injected into
      mature teratomas developed into tumors, which allowed tracking of tumor cell
      invasion and recruitment of human teratoma-derived blood vessels. This provides a
      straightforward and powerful approach to studying the biological properties of
      cancer cells within the microenvironment of normal differentiated human cells.

PMID- 14573706
TI  - Efficient oxidative folding of conotoxins and the radiation of venomous cone
      snails.
AB  - The 500 different species of venomous cone snails (genus Conus) use small, highly
      structured peptides (conotoxins) for interacting with prey, predators, and
      competitors. These peptides are produced by translating mRNA from many genes
      belonging to only a few gene superfamilies. Each translation product is processed
      to yield a great diversity of different mature toxin peptides (approximately
      50,000-100,000), most of which are 12-30 aa in length with two to three disulfide
      crosslinks. In vitro, forming the biologically relevant disulfide configuration
      is often problematic, suggesting that in vivo mechanisms for efficiently folding
      the diversity of conotoxins have been evolved by the cone snails. We demonstrate
      here that the correct folding of a Conus peptide is facilitated by a
      posttranslationally modified amino acid, gamma-carboxyglutamate. In addition, we
      show that multiple isoforms of protein disulfide isomerase are major soluble
      proteins in Conus venom duct extracts. The results provide evidence for the type
      of adaptations required before cone snails could systematically explore the
      specialized biochemical world of "microproteins" that other organisms have not
      been able to systematically access. Almost certainly, additional specialized
      adaptations for efficient microprotein folding are required.

PMID- 14573707
TI  - Pheromone-mediated gene expression in the honey bee brain.
AB  - We tested the hypothesis that queen mandibular pheromone (QMP) causes changes in
      gene expression in the brain of the adult worker honey bee, and that these
      changes can be correlated to the downstream behavioral responses induced by QMP.
      In support of the first hypothesis, cage experiments revealed that QMP
      transiently regulated expression of several hundred genes and chronically
      regulated the expression of 19 genes. Several of these genes were also affected
      by QMP in experiments with bee colonies in the field, demonstrating robust gene
      regulation by pheromone. To evaluate the second hypothesis, we focused on one
      function of QMP: delaying the transition from working in the hive (e.g., brood
      care, or "nursing") to foraging. We compared the list of QMP-regulated genes with
      the lists of genes differentially regulated in nurse and forager brains generated
      in a separate study. QMP consistently activated "nursing genes" and repressed
      "foraging genes," suggesting that QMP may delay behavioral maturation by
      regulating genes in the brain that produce these behavioral states. We also
      report here on an ortholog of the Drosophila transcription factor kruppel homolog
      1 that was strongly regulated by QMP, especially in the mushroom bodies of the
      bee brain. These results demonstrate chronic gene regulation by a primer
      pheromone and illustrate the potential of genomics to trace the actions of a
      pheromone from perception to action, and thereby provide insights into how
      pheromones regulate social life.

PMID- 14573708
TI  - Cancer incidence in airline cabin crew.

PMID- 14573709
TI  - Breast cancer risk in airline cabin attendants: a nested case-control study in
      Iceland.
AB  - AIMS: To investigate whether length of employment as a cabin attendant was
      related to breast cancer risk, when adjusted for reproductive factors. METHODS:
      Age matched case-control study nested in a cohort of cabin attendants. The cases
      were found from a nationwide cancer registry (followed up to end of year 2000)
      and the reproductive factors (age at first childbirth and number of children)
      from a registry of childbirth, in both instances by record linkage with the cabin
      attendants' identification numbers. The employment time of the cabin attendants
      at the airline companies and the reproductive factors had been systematically
      recorded prior to the diagnosis of breast cancer in the cohort. A total of 35
      breast cancer cases and 140 age matched controls selected from a cohort of 1532
      female cabin attendants were included in the study. RESULTS: The matched odds
      ratio from conditional logistic regression of breast cancer risk among cases and
      controls of cabin attendants was 5.24 (95% CI 1.58 to 17.38) for those who had
      five or more years of employment before 1971 compared with those with less than
      five years of employment before 1971, adjusted for age at first childbirth and
      length of employment from 1971 or later. CONCLUSIONS: The association between
      length of employment and risk of breast cancer, adjusted for reproductive
      factors, indicates that occupational factors may be an important cause of breast
      cancer among cabin attendants; the association is compatible with a long
      induction period.

PMID- 14573710
TI  - Cancer incidence in airline cabin crew: experience from Sweden.
AB  - AIMS: To determine the cancer incidence in Swedish cabin crew. METHODS: Cancer
      incidence of cabin crew at the Swedish Scandinavian Airline System (SAS) (2324
      women and 632 men) employed from 1957 to 1994 was determined during 1961-96 from
      the Swedish National Cancer Register. The cancer incidence in cabin crew was
      compared with that of the general Swedish population by comparing observed and
      expected number of cases through standardised incidence ratios (SIR). A nested
      case-control study was performed, including cancer cases diagnosed after 1979 and
      four controls per case matched by gender, age, and calendar year. RESULTS: The
      SIR for cancer overall was 1.01 (95% CI 0.78 to 1.24) for women and 1.16 (95% CI
      0.76 to 1.55) for men. Both men and women had an increased incidence of malignant
      melanoma of the skin (SIR 2.18 and 3.66 respectively) and men of non-melanoma
      skin cancer (SIR 4.42). Female cabin attendants had a non-significant increase of
      breast cancer (SIR 1.30; 95% CI 0.85 to 1.74). No clear associations were found
      between length of employment or cumulative block hours and cancer incidence.
      CONCLUSIONS: Swedish cabin crew had an overall cancer incidence similar to that
      of the general population. An increased incidence of malignant melanoma and non
      melanoma skin cancer may be associated with exposure to UV radiation, either at
      work or outside work. An increased risk of breast cancer in female cabin crew is
      consistent with our results and may in part be due to differences in reproductive
      history.

PMID- 14573711
TI  - Risk factors for cutaneous malignant melanoma among aircrews and a random sample
      of the population.
AB  - AIMS: To evaluate whether a difference in the prevalence of risk factors for
      malignant melanoma in a random sample of the population and among pilots and
      cabin attendants could explain the increased incidence of malignant melanoma
      which had been found in previous studies of aircrews. METHODS: A questionnaire
      was used to collect information on hair colour, eye colour, freckles, number of
      naevi, family history of skin cancer and naevi, skin type, history of sunburn,
      sunbed, all sunscreen use, and number of sunny vacations. RESULTS: The 239 pilots
      were all males and there were 856 female cabin attendants, which were compared
      with 454 males and 1464 females of the same age drawn randomly from the general
      population. The difference in constitutional and behavioural risk factors for
      malignant melanoma between the aircrews and the population sample was not
      substantial. The aircrews had more often used sunscreen and had taken more sunny
      vacations than the other men and women. The predictive values for use of
      sunscreen were 0.88 for pilots and 0.85 for cabin attendants and the predictive
      values for sunny vacation were 1.36 and 1.34 respectively. CONCLUSION: There was
      no substantial difference between the aircrew and the random sample of the
      population with respect to prevalence of risk factors for malignant melanoma.
      Thus it is unlikely that the increased incidence of malignant melanoma found in
      previous studies of pilots and cabin attendants can be solely explained by
      excessive sun exposure.

PMID- 14573712
TI  - Occupational risk factors for symptomatic lumbar disc herniation; a case-control
      study.
AB  - BACKGROUND: Previous studies mostly did not separate between symptomatic disc
      herniation combined with osteochondrosis/spondylosis of the lumbar spine and
      symptomatic disc herniation in radiographically normal intervertebral spaces.
      This may at least in part explain the differences in the observed risk patterns.
      AIMS: To investigate the possible aetiological relevance of physical and
      psychosocial workload to lumbar disc herniation with and without concomitant
      osteochondrosis/spondylosis. METHODS: A total of 267 cases with acute lumbar disc
      herniation (in two practices and four clinics) and 197 control subjects were
      studied. Data were gathered in a structured personal interview and analysed using
      logistic regression to control for age, region, nationality, and diseases
      affecting the lumbar spine. Cases without knowledge about
      osteochondrosis/spondylosis (n=42) were excluded from analysis. Risk factors were
      examined separately for those cases with (n=131) and without (n=94)
      radiographically diagnosed concomitant osteochondrosis or spondylosis. RESULTS:
      There was a statistically significant positive association between extreme
      forward bending and lumbar disc herniation with, as well as without concomitant
      osteochondrosis/spondylosis. There was a statistically significant relation
      between cumulative exposure to weight lifting or carrying and lumbar disc
      herniation with, but not without, concomitant osteochondrosis/spondylosis. Cases
      with disc herniation reported time pressure at work as well as psychic strain
      through contact with clients more frequently than control subjects. CONCLUSIONS:
      Further larger studies are needed to verify the concept of distinct aetiologies
      of lumbar disc herniation in relatively younger persons with otherwise normal
      discs and of disc herniation in relatively older persons with structurally
      damaged discs.

PMID- 14573713
TI  - Healthy worker effect and changes in respiratory symptoms and lung function in
      hairdressing apprentices.
AB  - AIMS: To compare the prevalence and incidence of respiratory symptoms and lung
      function values between hairdressing apprentices and office apprentices. METHODS:
      A total of 322 hairdressing apprentices and 277 office apprentices (controls)
      were studied. Two cross sectional surveys were conducted in 1994 and 1996/97 with
      longitudinal follow up for a subgroup of apprentices (191 hairdressing
      apprentices and 189 office apprentices). RESULTS: In the initial phase, the
      prevalence of respiratory symptoms was significantly lower among hairdressing
      apprentices than among office apprentices. Lung function test results showed
      significantly higher values for hairdressing apprentices. Non-specific bronchial
      reactivity was similar in the two groups. In the final phase, results for
      respiratory symptoms were similar. The incidence of respiratory symptoms was not
      significantly different between hairdressing apprentices and office apprentices.
      Subjects who dropped out had lower values for FVC and FEV1 in the initial phase
      than those who completed the final phase. There was a significant deterioration
      of FEV1 and FEF25-75% in hairdressing apprentices compared to office apprentices.
      There was a link between atopy and the incidence of most of the respiratory
      symptoms (day/night cough, wheezing, dyspnoea, mucosal hyperresponsiveness) and
      between smoking and the incidence of bronchial hyperreactivity. There was no
      significant correlation between change in lung function tests and specific
      hairdressing activities reported at the end of the apprenticeship or with
      environmental working conditions in hairdressing salons. CONCLUSIONS: Although a
      healthy worker effect can be suspected, results showed a significant
      deterioration of baseline values of lung function tests in the hairdressing
      apprentice group. However, no clear link was shown between change in lung
      function tests and specific parameters of occupational activities.

PMID- 14573714
TI  - Effects of a home exercise programme on shoulder pain and functional status in
      construction workers.
AB  - BACKGROUND: Repetitive or sustained elevated shoulder postures have been
      identified as a significant risk factor for occupationally related shoulder
      musculoskeletal disorders. Construction workers exposed to routine overhead work
      have high rates of shoulder pain that frequently progresses to functional loss
      and disability. Exercise interventions have potential for slowing this
      progression. AIMS: To evaluate a therapeutic exercise programme intended to
      reduce pain and improve shoulder function. METHODS: Construction worker
      volunteers were screened by history and clinical examination to test for
      inclusion/exclusion criteria consistent with shoulder pain and impingement
      syndrome. Sixty seven male symptomatic workers (mean age 49) were randomised into
      a treatment intervention group (n = 34) and a control group (n = 33);
      asymptomatic subjects (n = 25) participated as an additional control group.
      Subjects in the intervention group were instructed in a standardised eight week
      home exercise programme of five shoulder stretching and strengthening exercises.
      Subjects in the control groups received no intervention. Subjects returned after
      8-12 weeks for follow up testing. RESULTS: The intervention group showed
      significantly greater improvements in the Shoulder Rating Questionnaire (SRQ)
      score and shoulder satisfaction score than the control groups. Average post-test
      SRQ scores for the exercise group remained below levels for asymptomatic workers.
      Intervention subjects also reported significantly greater reductions in pain and
      disability than controls. CONCLUSIONS: Results suggest a home exercise programme
      can be effective in reducing symptoms and improving function in construction
      workers with shoulder pain.

PMID- 14573715
TI  - Mechanical and psychosocial factors predict new onset shoulder pain: a
      prospective cohort study of newly employed workers.
AB  - AIM: To test the hypothesis that work related mechanical and psychosocial factors
      predict new onset shoulder pain in newly employed workers. METHODS: Two year
      prospective study of newly employed workers from 12 diverse occupational
      settings. At baseline, 1081 subjects provided information on work related
      mechanical and psychosocial risk factors, and current pain status. RESULTS: In
      all, 803 (74%) subjects were free from shoulder pain at baseline. Of those, 638
      (79%) responded at 12 months and 476 (88%) at 24 months. New onset shoulder pain
      was reported by 93 (15%) and 73 (15%) subjects respectively. An increased risk of
      symptom onset was found in subjects reporting mechanical exposures involving
      heavy weights including lifting with one or two hands, carrying on one shoulder,
      lifting at or above shoulder level, and pushing or pulling. Working with hands
      above shoulder level was also predictive of new onset shoulder pain. Of the
      psychosocial factors examined, the strongest predictor was monotonous work. Those
      individuals with any other previous pain also had an increased risk of new onset
      shoulder pain at follow up. In multivariate analysis, lifting heavy weights with
      one or two hands, pushing or pulling heavy weights, working with hands above
      shoulder level, and monotonous work were independently associated with new onset
      shoulder pain. CONCLUSIONS: This study supports the hypothesised relation between
      mechanical risk factors and shoulder pain. In general, work related psychosocial
      factors were modestly associated with new onset shoulder pain. However,
      monotonous work was a strong risk factor for new onset shoulder pain.

PMID- 14573716
TI  - Respiratory status in dairy farmers in France; cross sectional and longitudinal
      analyses.
AB  - AIMS: To compare respiratory status in dairy farmers with that of non-farming
      controls. METHODS: Longitudinal study in the Doubs (France). From a cohort
      constituted in 1994 (T1), 215 (81.1%) dairy farmers and 110 (73.8%) controls were
      reevaluated in 1999 (T2). The protocol comprised a medical and occupational
      questionnaire, spirometric tests at both evaluations, allergological tests at T1,
      and a non-invasive measure of blood oxygen saturation (SpO2) at T2. RESULTS: In
      1999 analyses, the prevalence of chronic bronchitis was higher (p = 0.013), and
      FEV1/VC (p < 0.025) and SpO2 (-0.7%, p < 0.01) lower in dairy farmers than in
      controls. In a multiple linear regression model, farming, age, and smoking were
      significantly and inversely correlated with SpO2. In the whole population, the
      mean annual decline in FEV1 and FEV1/VC was -13.4 ml and -0.30%, respectively.
      Farming was associated with an accelerated decline in FEV1/VC (p < 0.025) after
      adjustment for covariates. No relation between allergy and respiratory function
      changes was observed, except for FEF25-75. CONCLUSIONS: This prospective study
      shows that dairy farming is associated with an excess of chronic bronchitis, with
      a moderate degree of bronchial obstruction and a mild decrease in SpO2.

PMID- 14573717
TI  - Risk factors for incident neck and shoulder pain in hospital nurses.
AB  - AIM: To assess the incidence and risk factors for neck and shoulder pain in
      nurses. METHODS: A longitudinal study of neck and shoulder pain was carried out
      in female nurses at two hospitals in England. Personal and occupational risk
      factors were assessed at baseline. The self reported incidence of symptoms in the
      neck and shoulder region was ascertained at three-monthly intervals over two
      years. A Cox regression model was used to estimate hazard ratios (HRs) for
      incident neck/shoulder pain during follow up in nurses who had been pain free for
      at least one month at baseline. RESULTS: The baseline response rate was 56%. Of
      903 women who were pain free at baseline, 587 (65%) completed at least one follow
      up while still in the same job. During an average of 13 months, 34% of these (202
      women) reported at least one episode of neck/shoulder pain. The strongest
      predictor of pain in the neck/shoulder was previous history of the symptom (HRs
      up to 3.3). For physical exposures at work, the highest risks (HRs up to 1.7)
      were associated with specific patient handling tasks that involved reaching,
      pushing, and pulling. Nurses who reported low mood or stress at baseline were
      more likely to develop neck/shoulder pain later (HR 1.5). Workplace psychosocial
      factors (including job demands, satisfaction, and control) were not associated
      with incident neck/shoulder symptoms. CONCLUSIONS: Neck/shoulder pain is common
      among hospital nurses, and patient handling tasks that involve reaching and
      pulling are the most important target for risk reduction strategies.

PMID- 14573718
TI  - Lung function decline in laboratory animal workers: the role of sensitisation and
      exposure.
AB  - BACKGROUND: Little is known about the relation between allergic sensitisation and
      subsequent long term lung function changes in working populations exposed to
      sensitising agents. AIMS: To investigate whether exposure and work related
      sensitisation to laboratory animals are associated with lung function decline.
      METHODS: The relation between exposure and sensitisation to laboratory animal
      allergens and changes in lung function was investigated in a longitudinal study
      (median follow up 2.0 years) among 319 laboratory animal workers. Subjects who
      had been working with laboratory animals for less than 4 years (n = 102) were
      analysed separately, since an earlier cross sectional analysis had suggested a
      strong healthy worker effect in more experienced workers. RESULTS: In multiple
      regression analyses both sensitisation and exposure appeared to contribute
      independently to lung function decline in subjects who had been working with
      laboratory animals for less than 4 years, adjusting for gender, age, smoking, and
      atopy. Lung function decline was most pronounced in sensitised subjects who
      continued to be in contact with the animals to which they were sensitised, with
      estimated average excess declines in FEV1, FVC, and MMEF of 83 ml/y (p < 0.05),
      148 ml/y (p < 0.01), and 7 ml/s/y (p = 0.9). CONCLUSIONS: We conclude that
      exposure to laboratory animals is a significant risk factor for accelerated lung
      function decline, and that sensitised workers are especially at risk.

PMID- 14573719
TI  - NO2, as a marker of air pollution, and recurrent wheezing in children: a nested
      case-control study within the BAMSE birth cohort.
AB  - AIMS: To investigate the association between air pollution, including with NO2,
      and recurrent wheezing during the first two years of life. METHODS: A birth
      cohort (BAMSE) comprised 4089 children, for whom information on exposures,
      symptoms, and diseases was available from parental questionnaires at ages 2
      months, and 1 and 2 years. NO2 was measured during four weeks in and outside the
      dwellings of children with recurrent wheezing and two age matched controls, in a
      nested case-control study (540 children). RESULTS: Conditional logistic
      regression showed an OR of 1.60 (95% CI 0.78 to 3.26) among children in the
      highest quartile of outdoor NO2 exposure in relation to those in the lowest
      quartile, adjusted for potential confounders. The corresponding OR for indoor NO2
      was 1.51 (95% CI 0.81 to 2.82). An interaction with environmental tobacco smoke
      (ETS) was indicated with an OR of 3.10 (95% CI 1.32 to 7.30) among children
      exposed to the highest quartile of indoor NO2 and ETS. The association between
      NO2 and recurrent wheezing appeared stronger in children who did not fulfil the
      criteria for recurrent wheezing until their second year. CONCLUSIONS: Although
      the odds of increased recurrent wheezing are not statistically significantly
      different from one, results suggest that exposure to air pollution including NO2,
      particularly in combination with exposure to ETS, increases the risk of recurrent
      wheezing in children.

PMID- 14573720
TI  - Primary osteoarthritis and occupations: a national cross sectional survey of 10
      412 symptomatic patients.
AB  - AIMS: To describe the age standardised prevalence of symptomatic osteoarthritis
      (OA) in a nationwide cross sectional survey of 10 412 patients in France, and
      their functional and work limitations. METHODS: Cases in the survey were compared
      with their expected counterpart by age, gender, and occupational groupings using
      data from the 1998 French National Survey on Health Impairment and Disability.
      RESULTS: Women represented 66.2% of the sample; mean age was 66.2 years. One
      third of patients had OA of the knee, 16% of the hip, and 12% of the hand; a
      third had multiple joint OA. Peak prevalence of symptomatic OA was in the 60-69
      year category in women and in the 70-79 year category in men. Agricultural
      workers showed a significant excess prevalence of OA, with an observed to
      expected (O/E) ratio of 1.7 in women and 2.3 in men. Linear trends in prevalences
      between white collar, "mixed" collar, and blue collar workers were also
      significant, with odds ratios respectively of 1.0, 2.9, and 2.6 in women and 1.0,
      1.2, and 1.7 in men. Specific excess prevalence was found in women among
      housekeepers (O/E 4.4), and in men among unskilled labour workers (O/E 10.3) and
      truck drivers (O/E 6.7). Total work disability was highest among blue collar
      workers and partial disability among agricultural workers. CONCLUSION: Results
      contribute to the mounting evidence that OA is potentially aetiologically linked
      to occupation in a sizeable segment of the population and that OA can no longer
      be considered an inevitable disease of ageing.

PMID- 14573721
TI  - Does psychological distress influence reporting of demands and control at work?
AB  - AIMS: To investigate whether self reporting of psychological demands and control
      at work is as valid for psychologically distressed subjects as for subjects with
      psychological wellbeing. METHOD: Self reported demands and control (according to
      the model of Karasek) were compared to expert assessments through direct
      observations of each subject's work conditions concerning time pressure,
      hindrances, qualification for work tasks, and possibility of having influence.
      The comparison was made between respondents reporting and not reporting
      psychological distress as measured by the general health questionnaire with 12
      questions (GHQ-12). The sample consisted of 203 men and women in 85 occupations.
      RESULT: No systematic differences between self reported and externally assessed
      working conditions for respondents reporting different levels of psychological
      distress were found. CONCLUSION: Over-reporting of work demands or under
      reporting of work control is unlikely at the levels of psychological distress
      studied.

PMID- 14573723
TI  - The silica carcinogenicity issue in Japan.

PMID- 14573722
TI  - Repeated daily exposure to 2 ppm nitrogen dioxide upregulates the expression of
      IL-5, IL-10, IL-13, and ICAM-1 in the bronchial epithelium of healthy human
      airways.
AB  - BACKGROUND: Repeated daily exposure of healthy human subjects to NO2 induces an
      acute airway inflammatory response characterised by neutrophil influx in the
      bronchial mucosa AIMS: To assess the expression of NF-kappaB, cytokines, and ICAM
      1 in the bronchial epithelium. METHODS: Twelve healthy, young non-smoking
      volunteers were exposed to 2 ppm of NO2/filtered air (four hours/day) for four
      successive days on separate occasions. Fibreoptic bronchoscopy was performed one
      hour after air and final NO2 exposures. Bronchial biopsy specimens were
      immunostained for NF-kappaB, TNF-alpha, eotaxin, Gro-alpha, GM-CSF, IL-5, -6, -8,
      -10, -13, and ICAM-1 and their expression was quantified using computerised image
      analysis. RESULTS: Expression of IL-5, IL-10, IL-13, and ICAM-1 increased
      following NO2 exposure. CONCLUSION: Upregulation of the Th2 cytokines suggests
      that repeated exposure to NO2 has the potential to exert a "pro-allergic" effect
      on the bronchial epithelium. Upregulation of ICAM-1 highlights an underlying
      mechanism for leucocyte influx, and could also explain the predisposition to
      respiratory tract viral infections following NO2 exposure since ICAM-1 is a major
      receptor for rhino and respiratory syncytial viruses.

PMID- 14573724
TI  - The impact of a week of simulated night work on sleep, circadian phase, and
      performance.
AB  - AIMS: To investigate factors that may contribute to performance adaptation during
      permanent night work. METHODS: Fifteen healthy subjects participated in an
      adaptation and baseline night sleep, directly followed by seven simulated eight
      hour night shifts (2300 to 0700 hours). At the end of each shift they were taken
      outside and exposed to natural light for 20 minutes. They then slept from
      approximately 0800 hours until they naturally awoke. RESULTS: There was a
      significant increase in mean performance on a visual psychomotor vigilance task
      across the week. Daytime sleep quality and quantity were not negatively affected.
      Total sleep time (TST) for each of the daytime sleeps was reduced, resulting in
      an average cumulative sleep debt of 3.53 hours prior to the final night shift.
      TST for each of the daytime sleep periods did not significantly differ from the
      baseline night, nor did TST significantly vary across the week. There was a
      significant decrease in wake time after sleep onset and sleep onset latency
      across the week; sleep efficiency showed a trend towards greater efficiency
      across the consecutive daytime sleeps. Hours of wakefulness prior to each
      simulated night shift significantly varied across the week. The melatonin profile
      significantly shifted across the week. CONCLUSIONS: Results suggest that under
      optimal conditions, the sleep debt that accumulates during consecutive night
      shifts is relatively small and does not exacerbate decrements in night-time
      performance resulting from other factors. When sleep loss is minimised,
      adaptation of performance during consecutive night shifts can occur in
      conjunction with circadian adaptation.

PMID- 14573725
TI  - Does computer use pose an occupational hazard for forearm pain; from the NUDATA
      study.
AB  - AIMS: To determine the occurrence of pain conditions and disorders in the forearm
      and to evaluate risk factors for forearm pain in a cohort of computer workers.
      METHODS: A total of 6943 participants with a wide range of computer use and work
      tasks were studied. At baseline and at one year follow up participants completed
      a questionnaire. Participants with relevant forearm symptoms were offered a
      clinical examination. Symptom cases and clinical cases were defined on the basis
      of self reported pain score and palpation tenderness in the muscles of the
      forearm. RESULTS: The seven days prevalence of moderate to severe forearm pain
      was 4.3%. Sixteen of 296 symptom cases met criteria for being a clinical forearm
      case, and 12 had signs of potential nerve entrapment. One year incidence of
      reported symptom cases was 1.3%; no subjects developed new signs of nerve
      entrapment. Increased risk of new forearm pain was associated with use of a mouse
      device for more than 30 hours per week, and with keyboard use more than 15 hours
      per week. High job demands and time pressure at baseline were risk factors for
      onset of forearm pain; women had a twofold increased risk of developing forearm
      pain. Self reported ergonomic workplace factors at baseline did not predict
      future forearm pain. CONCLUSION: Intensive use of a mouse device, and to a lesser
      extent keyboard usage, were the main risk factors for forearm pain. The
      occurrence of clinical disorders was low, suggesting that computer use is not
      commonly associated with any severe occupational hazard to the forearm.

PMID- 14573726
TI  - The effect of sulphurous air pollutant exposures on symptoms, lung function,
      exhaled nitric oxide, and nasal epithelial lining fluid antioxidant
      concentrations in normal and asthmatic adults.
AB  - AIMS: To explore the effects in normal and asthmatic adults of exposure to 200
      ppb sulphur dioxide (SO2) and 200 microg/m3 and 2000 microg/m3 aerosols of
      ammonium bisulphate (AB) and sulphuric acid (SA) (MMD 0.3 microm). METHODS:
      Exposures were placebo controlled, for one hour at rest, double blind in random
      order. DeltaFEV1 was the primary outcome; secondary outcomes included symptoms,
      ventilation, exhaled nitric oxide (NO) concentrations, and nasal lavage fluid
      ascorbic (AA) and uric acid (UA) concentrations. RESULTS: There were no
      significant changes in spirometry or symptoms with any exposure in either group.
      SO2 exposure was associated with an increased respiratory rate relative to air
      exposure in the asthmatic group (SO2: 958.9 breaths/hour; air: 906.8
      breaths/hour) but the mean volume breathed did not differ significantly (SO2:
      318.8 litres; air: 311.4 litres). AB exposures were associated with a significant
      rise in [NO] in the asthmatic (+1.51 ppb, and +1.39 ppb), but not in the normal
      group. Mean pre- and post-exposure [AA] tended to be higher in the normal than in
      the asthmatic group. Within each group, [AA] did not change significantly with
      any exposure. Post-exposure [UA] were greater than pre-exposure concentrations
      for all exposures, significantly so in the normal group for all exposures except
      SO2. There were no significant differences in the mean change in [UA] for any
      exposure relative to air. CONCLUSIONS: The pollutant exposure concentrations
      employed in this study were generally much greater than ambient. It is unlikely
      that short lived exposures at lower concentrations would show significant
      effects, but effects of longer term lower concentration exposures cannot be ruled
      out.

PMID- 14573727
TI  - High local unemployment and increased mortality in Danish adults; results from a
      prospective multilevel study.
AB  - AIMS: To examine the relation between unemployment rates in area of residence and
      all-cause mortality, taking the individuals' unemployment experience and a number
      of social and behavioural factors into account. METHODS: Prospective cohort study
      with record linkage to mortality and unemployment registers. Data were pooled
      data from two population studies conducted in Copenhagen, Denmark. The
      association between unemployment at parish level and mortality was examined in
      Cox proportional hazard analysis. A total of 15 980 men and women, aged 20-67
      years and employed at 1 January 1980, were studied. All-cause mortality was
      followed from January 1981 to December 1998. RESULTS: The unemployment rate in
      the area of residence was associated with increased mortality (hazard
      ratio(highest v lowest quartile) 1.35:0.14-1.60) even after adjustment for
      individuals' unemployment experience in 1980, which was also a risk factor
      (hazard ratio(yes/no) 1.38:1.16-1.64). These estimates attenuated somewhat when
      other social and behavioural covariates were taken into account. The effects were
      similar in men and women, but the influence of individuals' unemployment
      experience during one and five years decreased gradually with increasing age.
      CONCLUSION: This prospective study suggests that high local unemployment and
      individuals' experience of unemployment increase mortality risk, even after
      adjustment for other social and behavioural factors.

PMID- 14573728
TI  - Novel risk markers and clinical practice.

PMID- 14573729
TI  - Bench and bedside--the G protein-coupled receptor GPR54 and puberty.

PMID- 14573730
TI  - Population-based studies of adverse drug effects.

PMID- 14573731
TI  - Prognostic value of myeloperoxidase in patients with chest pain.
AB  - BACKGROUND: Inflammation is linked to adverse outcomes in acute coronary
      syndromes. Myeloperoxidase, an abundant leukocyte enzyme, is elevated in culprit
      lesions that have fissured or ruptured in patients with sudden death from cardiac
      causes. Numerous lines of evidence suggest mechanistic links between
      myeloperoxidase and both inflammation and cardiovascular disease. METHODS: We
      assessed the value of plasma levels of myeloperoxidase as a predictor of the risk
      of cardiovascular events in 604 sequential patients presenting to the emergency
      department with chest pain. RESULTS: Initial plasma myeloperoxidase levels
      predicted the risk of myocardial infarction, even in patients who are negative
      for troponin T (<0.1 ng per milliliter) at base line (P<0.001). Myeloperoxidase
      levels at presentation also predicted the risk of major adverse cardiac events
      (myocardial infarction, the need for revascularization, or death) within 30 days
      and 6 months after presentation (P<0.001). In patients without evidence of
      myocardial necrosis (defined as those who were negative for troponin T), the base
      line myeloperoxidase levels independently predicted the risk of major adverse
      coronary events at 30 days (unadjusted 2nd, 3rd, and 4th quartile odds ratios,
      2.2 [95 percent confidence interval, 1.1 to 4.6], 4.2 [95 percent confidence
      interval, 2.1 to 8.4], and 4.1 [95 percent confidence interval, 2.0 to 8.4],
      respectively) and at 6 months. CONCLUSIONS: A single initial measurement of
      plasma myeloperoxidase independently predicts the early risk of myocardial
      infarction, as well as the risk of major adverse cardiac events in the ensuing 30
      day and 6-month periods. Myeloperoxidase levels, in contrast to troponin T,
      creatine kinase MB isoform, and C-reactive protein levels, identified patients at
      risk for cardiac events in the absence of myocardial necrosis, highlighting its
      potential usefulness for risk stratification among patients who present with
      chest pain.

PMID- 14573732
TI  - Glutathione peroxidase 1 activity and cardiovascular events in patients with
      coronary artery disease.
AB  - BACKGROUND: Cellular antioxidant enzymes such as glutathione peroxidase 1 and
      superoxide dismutase have a central role in the control of reactive oxygen
      species. In vitro data and studies in animal models suggest that these enzymes
      may protect against atherosclerosis, but little is known about their relevance to
      human disease. METHODS: We conducted a prospective study among 636 patients with
      suspected coronary artery disease, with a median follow-up period of 4.7 years
      (maximum, 5.4) to assess the risk of cardiovascular events associated with base
      line erythrocyte glutathione peroxidase 1 and superoxide dismutase activity.
      RESULTS: Glutathione peroxidase 1 activity was among the strongest univariate
      predictors of the risk of cardiovascular events, whereas superoxide dismutase
      activity had no association with risk. The risk of cardiovascular events was
      inversely associated with increasing quartiles of glutathione peroxidase 1
      activity (P for trend <0.001); patients in the highest quartile of glutathione
      peroxidase 1 activity had a hazard ratio of 0.29 (95 percent confidence interval,
      0.15 to 0.58; P<0.001), as compared with those in the lowest quartile.
      Glutathione peroxidase 1 activity was affected by sex and smoking status but
      retained its predictive power in these subgroups. After adjustment for these and
      other cardiovascular risk factors, the inverse association between glutathione
      peroxidase 1 activity and cardiovascular events remained nearly unchanged.
      CONCLUSIONS: In patients with coronary artery disease, a low level of activity of
      red-cell glutathione peroxidase 1 is independently associated with an increased
      risk of cardiovascular events. Glutathione peroxidase 1 activity may have
      prognostic value in addition to that of traditional risk factors. Furthermore,
      increasing glutathione peroxidase 1 activity might lower the risk of
      cardiovascular events.

PMID- 14573733
TI  - The GPR54 gene as a regulator of puberty.
AB  - BACKGROUND: Puberty, a complex biologic process involving sexual development,
      accelerated linear growth, and adrenal maturation, is initiated when gonadotropin
      releasing hormone begins to be secreted by the hypothalamus. We conducted studies
      in humans and mice to identify the genetic factors that determine the onset of
      puberty. METHODS: We used complementary genetic approaches in humans and in mice.
      A consanguineous family with members who lacked pubertal development (idiopathic
      hypogonadotropic hypogonadism) was examined for mutations in a candidate gene,
      GPR54, which encodes a G protein-coupled receptor. Functional differences between
      wild-type and mutant GPR54 were examined in vitro. In parallel, a Gpr54-deficient
      mouse model was created and phenotyped. Responsiveness to exogenous gonadotropin
      releasing hormone was assessed in both the humans and the mice. RESULTS: Affected
      patients in the index pedigree were homozygous for an L148S mutation in GPR54,
      and an unrelated proband with idiopathic hypogonadotropic hypogonadism was
      determined to have two separate mutations, R331X and X399R. The in vitro
      transfection of COS-7 cells with mutant constructs demonstrated a significantly
      decreased accumulation of inositol phosphate. The patient carrying the compound
      heterozygous mutations (R331X and X399R) had attenuated secretion of endogenous
      gonadotropin-releasing hormone and a left-shifted dose-response curve for
      gonadotropin-releasing hormone as compared with six patients who had idiopathic
      hypogonadotropic hypogonadism without GPR54 mutations. The Gpr54-deficient mice
      had isolated hypogonadotropic hypogonadism (small testes in male mice and a delay
      in vaginal opening and an absence of follicular maturation in female mice), but
      they showed responsiveness to both exogenous gonadotropins and gonadotropin
      releasing hormone and had normal levels of gonadotropin-releasing hormone in the
      hypothalamus. CONCLUSIONS: Mutations in GPR54, a G protein-coupled receptor gene,
      cause autosomal recessive idiopathic hypogonadotropic hypogonadism in humans and
      mice, suggesting that this receptor is essential for normal gonadotropin
      releasing hormone physiology and for puberty.

PMID- 14573734
TI  - Absence of cross-reactivity between sulfonamide antibiotics and sulfonamide
      nonantibiotics.
AB  - BACKGROUND: The safety of sulfonamide nonantibiotics is unclear in patients with
      prior allergic reactions to sulfonamide antibiotics. METHODS: We conducted a
      retrospective cohort study using the General Practice Research Database in the
      United Kingdom, examining the risk of allergic reactions within 30 days after the
      receipt of a sulfonamide nonantibiotic. Patients with evidence of prior
      hypersensitivity after the receipt of a sulfonamide antibiotic were compared with
      those without such evidence. Similar analyses were also performed with the use of
      penicillins instead of sulfonamides, to determine whether any risk was specific
      to sulfonamide cross-reactivity. RESULTS: Of 969 patients with an allergic
      reaction after a sulfonamide antibiotic, 96 (9.9 percent) had an allergic
      reaction after subsequently receiving a sulfonamide nonantibiotic. Of 19,257 who
      had no allergic reaction after a sulfonamide antibiotic, 315 (1.6 percent) had an
      allergic reaction after receiving a sulfonamide nonantibiotic (adjusted odds
      ratio, 2.8; 95 percent confidence interval, 2.1 to 3.7). However, the risk of
      allergic reactions was even greater after the receipt of a penicillin among
      patients with a prior hypersensitivity reaction to a sulfonamide antibiotic, as
      compared with patients with no such history (adjusted odds ratio, 3.9; 95 percent
      confidence interval, 3.5 to 4.3). Furthermore, among those with a prior
      hypersensitivity reaction after the receipt of a sulfonamide antibiotic, the risk
      of an allergic reaction after the subsequent receipt of a sulfonamide
      nonantibiotic was lower than the risk of an allergic reaction after the
      subsequent receipt of a penicillin (adjusted odds ratio, 0.7; 95 percent
      confidence interval, 0.5 to 0.9). Finally, the risk of an allergic reaction after
      the receipt of a sulfonamide nonantibiotic was lower among patients with a
      history of hypersensitivity to sulfonamide antibiotics than among patients with a
      history of hypersensitivity to penicillins (adjusted odds ratio, 0.6; 95 percent
      confidence interval, 0.5 to 0.8). CONCLUSIONS: There is an association between
      hypersensitivity after the receipt of sulfonamide antibiotics and a subsequent
      allergic reaction after the receipt of a sulfonamide nonantibiotic, but this
      association appears to be due to a predisposition to allergic reactions rather
      than to cross-reactivity with sulfonamide-based drugs.

PMID- 14573735
TI  - Images in clinical medicine. Isolated right ventricular infarction.

PMID- 14573736
TI  - Hospital use and survival among Veterans Affairs beneficiaries.
AB  - BACKGROUND: Initiatives to reduce hospital care were part of the reorganization
      of the Department of Veterans Affairs (VA) medical care system undertaken in the
      mid-1990s. We examined changes in the use of VA health services and survival from
      1994 through 1998 among VA beneficiaries with serious chronic diseases. We
      postulated that if access to hospital care was reduced too much, or if decreased
      hospital use was not offset by improvements in ambulatory care, urgent care
      visits would increase or survival rates would fall. METHODS: We tracked changes
      in risk-adjusted VA bed-day rates, rates of medical visits, rates of visits for
      testing and consultation, and rates of urgent care visits per patient-year among
      VA beneficiaries in nine disease cohorts (a total of 342,300 beneficiaries).
      Trends in non-VA hospital use by VA beneficiaries 65 years of age or older who
      were enrolled in fee-for-service Medicare were also studied. VA and Medicare
      vital-status data were used to calculate one-year survival rates. RESULTS: From
      1994 through 1998, VA bed-day rates fell by 50 percent, rates of medical-clinic
      visits and visits for testing and consultation increased moderately, and rates of
      urgent care visits fell by 35 percent. The sharp decline in the use of VA
      hospitals was not compensated for by increases in the use of Medicare-reimbursed
      non-VA hospital care by veterans eligible for both VA care and Medicare, and the
      use of non-VA hospitals actually declined in four cohorts. The survival rates
      were essentially unchanged over the study period. CONCLUSIONS: The marked decline
      in VA hospital use from 1994 through 1998 did not curtail access to needed
      services and was not associated with serious consequences for chronically ill VA
      beneficiaries.

PMID- 14573737
TI  - Clinical practice. Gout.

PMID- 14573739
TI  - Medical care--is more always better?

PMID- 14573738
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 33-2003. A 37-year-old man with a history of alcohol and drug
      abuse and sudden onset of leg weakness.

PMID- 14573740
TI  - Bed covers and dust mites.

PMID- 14573741
TI  - Bone loss and bone size after menopause.

PMID- 14573742
TI  - Verification bias in screening for prostate cancer.

PMID- 14573743
TI  - Screening for celiac disease.

PMID- 14573744
TI  - Urinary tract infection.

PMID- 14573745
TI  - Bevacizumab in renal-cell cancer.

PMID- 14573746
TI  - Renal failure with the use of zoledronic acid.

PMID- 14573747
TI  - Images in clinical medicine. Splenic sarcoidosis.

PMID- 14573748
TI  - Pharmacological modulation of Poly(ADP-ribose) polymerase-mediated cell death:
      exploitation in cancer chemotherapy.

PMID- 14573749
TI  - Probing the roles of protein kinases in g-protein-coupled receptor
      desensitization.

PMID- 14573750
TI  - Expression of the aflatoxin B1-8,9-epoxide-metabolizing murine glutathione S
      transferase A3 subunit is regulated by the Nrf2 transcription factor through an
      antioxidant response element.
AB  - High expression of the aflatoxin B1 (AFB1)-8,9-epoxide-conjugating glutathione S
      transferase A3 (mGSTA3) subunit in mouse liver confers intrinsic resistance to
      AFB1 hepatocarcinogenesis. It is not known how the gene encoding this protein is
      regulated. The murine mGSTA3 gene has been identified using bioinformatics. It
      localizes to mouse chromosome 1 (A3-4), spans approximately 24.6 kilobases (kb)
      of DNA, and comprises seven exons. High levels of mGSTA3 mRNA are present in
      organs associated with detoxification. Expression of mGSTA3 in Hepa1c1c7 mouse
      hepatoma cells was found to be inducible by sulforaphane, an organic
      isothiocyanate that can transcriptionally activate genes through the antioxidant
      response element (ARE). Sulforaphane also induced transcription of a luciferase
      reporter containing a 1.5 kb fragment of the mGSTA3 5'-upstream region. A
      putative ARE, with sequence 5'-TGACATTGC-3', was identified within this fragment,
      approximately 150 base pairs upstream of exon 1. Mutation of this sequence
      abrogated both basal and sulforaphane-inducible reporter activity. Overexpression
      of the basic-region leucine zipper Nrf2 transcription factor augmented activity
      of the mGSTA3-luciferase reporter through this ARE. Electrophoretic mobility
      shift assays demonstrated that Nrf2 binds the mGSTA3 ARE. Measurement of mGSTA3
      mRNA levels in tissues isolated from both wild-type and nrf2-null mice revealed
      that loss of the Nrf2 transcription factor is associated with a reduction in
      basal expression of mGSTA3. Collectively, these data demonstrate a role for Nrf2
      and the ARE in regulating transcription of mGSTA3.

PMID- 14573751
TI  - Inhibition of vascular endothelial growth factor-induced angiogenesis by
      resveratrol through interruption of Src-dependent vascular endothelial cadherin
      tyrosine phosphorylation.
AB  - Resveratrol, a polyphenolic compound found in grapes and other fruits, has been
      reported to inhibit angiogenesis with an as yet elusive mechanism. Here, we
      investigate the detailed mechanism by which resveratrol inhibits vascular
      endothelial growth factor (VEGF)-induced angiogenic effects in human umbilical
      endothelial cells (HUVECs). Exposure of HUVECs to 1 to 2.5 muM resveratrol
      significantly blocked VEGF-mediated migration and tube formation but not cell
      proliferation. Under the same concentrations, resveratrol failed to affect VEGF
      stimulated activation of VEGF receptor, extracellular signal-regulated protein
      kinase 1/2, p38 mitogen-activated protein kinase, and Akt. Of interest,
      resveratrol, at the dose of 1 or 2.5 muM, effectively abrogated VEGF-mediated
      tyrosine phosphorylation of vascular endothelial (VE)-cadherin and its complex
      partner, beta-catenin. This inhibitory effect of resveratrol reflected on the
      retention of VE-cadherin at cell-cell contacts as demonstrated by
      immunofluorescence. Src kinase assay showed that VEGF-induced endogenous Src
      kinase activation was strongly inhibited by 1 and 2.5 muM resveratrol.
      Supportively, inhibition of Src activity by overexpression of Csk resulted in
      attenuation of the tyrosine phosphorylation of VE-cadherin and endothelial cell
      (EC) tube formation. Again, transfection with v-Src, an active form of Src, could
      reverse resveratrol inhibition of VE-cadherin tyrosine phosphorylation and EC
      tube formation. Reactive oxygen species (ROS) has been shown to be involved in VE
      cadherin phosphorylation and its related functions. Flow cytometric analysis
      showed that VEGF stimulated an evident increase of peroxide, which was strongly
      attenuated by resveratrol. In addition, antioxidant N-acetyl-cysteine was
      demonstrated to strongly inhibit VEGF-mediated Src activation, VE-cadherin
      tyrosine phosphorylation, and HUVEC tube formation. Together, our data suggest
      that resveratrol inhibition of VEGF-induced angiogenesis was mediated by
      disruption of ROS-dependent Src kinase activation and the subsequent VE-cadherin
      tyrosine phosphorylation.

PMID- 14573752
TI  - Different affinities of inhibitors to the outwardly and inwardly directed
      substrate binding site of organic cation transporter 2.
AB  - The rat organic cation transporter 2 (rOCT2) was expressed in Xenopus laevis
      oocytes and cation-induced outward and inward currents were measured in whole
      cells and giant patches using voltage clamp techniques. Tetrabutylammonium (TBuA)
      and corticosterone were identified as nontransported inhibitors that bind to the
      substrate binding site of rOCT2. They inhibited cation-induced currents from both
      membrane sides. Increased substrate concentrations could partially overcome the
      inhibition. At 0 mV, the affinity of TBuA from the extracellular side compared
      with the intracellular side of the membrane was 4-fold higher, whereas the
      affinity of corticosterone was 20-fold lower. The data suggest that the substrate
      binding site of rOCT2 is like a pocket containing overlapping binding domains for
      ligands. These binding domains may undergo separate structural changes. From the
      extracellular surface, the affinity for uncharged corticosterone was increased by
      making membrane potential more negative. This implies potential-dependent
      structural changes in the extracellular binding pocket and existence of a voltage
      sensor. Interestingly, at 0 mV, an 18-fold higher affinity was determined for
      trans-inhibition of choline efflux by corticosterone compared with cis-inhibition
      of choline uptake. This suggests an additional high affinity-conformation of the
      empty outwardly oriented substrate binding pocket. A model is proposed that
      describes how substrates and inhibitors might interact with rOCT2. The data
      provide a theoretical basis to understand drug-drug interactions at polyspecific
      transporters for organic cations.

PMID- 14573753
TI  - The third intracellular loop and the carboxyl terminus of beta2-adrenergic
      receptor confer spontaneous activity of the receptor.
AB  - It is well established that the beta2-adrenergic receptor (beta2-AR) exhibits a
      robust ligand-independent activity, whereas this property is considerably weaker
      in the closely related beta1-AR subtype. To identify the potential domain(s) of
      beta2-AR responsible for the spontaneous receptor activation, we created three
      chimeras in which the third intracellular loop (beta1/beta2-Li3) or the carboxyl
      terminus (beta1/beta2-CT) or both domains (beta1/beta2-Li3CT) of beta1-AR are
      replaced by the corresponding parts of the beta2-AR. Using adenoviral gene
      transfer, we individually expressed these beta1/beta2-AR chimeras in mouse
      cardiomyocytes lacking both native beta1-AR and beta2-AR (beta1/beta2 double
      knockout), and examined their possible spontaneous activities. Overexpression of
      these beta1/beta2-AR chimeras markedly elevated basal cAMP accumulation and
      myocyte contractility in the absence of agonist stimulation compared with those
      infected by a control adenovirus expressing beta-galactosidase or an adenovirus
      expressing wild type beta1-AR. These effects were fully reversed by a beta2-AR
      inverse agonist, (+/-)-1-[2,3-(dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1
      methylethyl)amino]-2-butanol (ICI 118,551; 5 x 10-7 M), regardless of inhibition
      of Gi with pertussis toxin, but not by a panel of beta1-AR antagonists, including
      [2-(3-carbamoyl-4-hydroxyphenoxy)-ethylamino]-3-[4-(1-methyl-4-trifluormethyl-2
      imidazolyl)-phenoxy]-2-propanolmethanesulfonate (CGP20712A), betaxolol,
      bisoprolol, and metoprolol. Furthermore, we have shown that the C-terminal
      postsynaptic density 95/disc-large/ZO-1 (PDZ) motif of beta1-AR is not
      responsible for the lack of beta1-AR spontaneous activation, although it has been
      known that the beta1-AR PDZ motif prevents the receptor from undergoing agonist
      induced trafficking and Gi coupling in cardiomyocytes. Taken together, the
      present results indicate that both the third intracellular loop and the C
      terminus are involved in beta2-AR spontaneous activation and that either domain
      seems to be sufficient to confer the receptor spontaneous activity.

PMID- 14573754
TI  - Specificity of g protein-coupled receptor kinase 6-mediated phosphorylation and
      regulation of single-cell m3 muscarinic acetylcholine receptor signaling.
AB  - Previously we have shown that G protein-coupled receptor kinase (GRK) 6 plays a
      major role in the regulation of the human M3 muscarinic acetylcholine receptor
      (M3 mAChR) in the human neuroblastoma SH-SY5Y. However, 30-fold overexpression of
      the catalytically inactive, dominant-negative K215RGRK6 produced only a 50%
      suppression of M3 mAChR phosphorylation and desensitization. Here, we have
      attempted to determine whether other endogenous kinases play a role in the
      regulation of M3 mAChR signaling. In contrast to the clear attenuating effect of
      K215RGRK6 expression on M3 mAChR regulation, dominant-negative forms of GRKs
      (K220RGRK2, K220RGRK3, K215RGRK5) and casein kinase 1alpha (K46RCK1alpha) were
      without effect. In addition, inhibition of a variety of second-messenger
      regulated kinases and the tyrosine kinase Src also had no effect upon agonist
      stimulated M3 mAChR regulation. To investigate further the desensitization
      process we have followed changes in inositol 1,4,5-trisphosphate in single SHSY5Y
      cells using the pleckstrin homology domain of PLCdelta1 tagged with green
      fluorescent protein (eGFP-PHPLCdelta1). Stimulation of cells with approximate
      EC50 concentrations of agonist before and after a desensitizing period of agonist
      exposure resulted in a marked attenuation of the latter response. Altered GRK6
      activity, through overexpression of wild-type GRK6 or K215RGRK6, enhanced or
      reduced the degree of M3 mAChR desensitization, respectively. Taken together, our
      data indicate that M3 mAChR desensitization is mediated by GRK6 in human SH-SY5Y
      cells, and we show that receptor desensitization of phospholipase C signaling can
      be monitored in 'real-time' in single, living cells.

PMID- 14573755
TI  - Cytoplasmic accumulation of the nuclear receptor CAR by a tetratricopeptide
      repeat protein in HepG2 cells.
AB  - The nuclear constitutive active receptor (CAR) is a key transcription factor
      regulating phenobarbital (PB)-inducible transcription of various hepatic genes
      that encode xenobiotic/steroid-metabolizing enzymes. CAR is retained in the
      cytoplasm of noninduced livers and translocates into the nucleus after PB
      induction. HepG2 cells lack the capability of retaining CAR in the cytoplasm;
      thus, the receptor spontaneously accumulates in the nucleus. We have now cloned
      and characterized a tetratricopeptide repeat (TPR) protein, designated
      cytoplasmic CAR retention protein (CCRP), for its ability to accumulate the
      receptor in the cytoplasm of cotransfected HepG2 cells. CCRP directly interacts
      with the ligand-binding domain of CAR and mediates the formation of a cytoplasmic
      CAR-CCRP-90-kDa heat shock protein (hsp90) ternary complex. Simultaneous
      expression of fluorescent protein-tagged CAR and CCRP reveals their
      colocalization with tubulin in mouse liver in vivo. Thus, these results indicate
      that CCRP may be a component of the CAR-hsp90 complex and involved in retaining
      the receptor in the cytoplasm of both HepG2 cells and probably in vivo liver
      cells.

PMID- 14573756
TI  - Inhibition of invasion and angiogenesis by zinc-chelating agent disulfiram.
AB  - Cell invasion and angiogenesis are crucial processes in cancer metastasis that
      require extracellular matrix (ECM) degradation. Proteolytic degradation of the
      ECM components is a central event of invasion and angiogenesis processes. During
      these processes, matrix metalloproteinases (MMPs) seem to be primarily
      responsible for much of the ECM degradation. Disulfiram is frequently used in the
      treatment of alcoholism and has been reported to possess antiretroviral activity
      and can eject intrinsic zinc out of human immunodeficiency virus (HIV)
      nucleocapsid protein. In this report, we show that disulfiram inhibited invasion
      and angiogenesis in both tumor and endothelial cells at nontoxic concentrations.
      The 3H-labeled type IV collagen degradation assay suggested that disulfiram has
      type IV collagenase inhibitory activity, and this inhibition was responsible for
      blocking invasion and angiogenesis through cell-mediated and non-cell-mediated
      pathways. However, the mechanisms underlying cell-mediated signal pathways are
      not fully characterized. Our data demonstrate that the non-cell-mediated pathway
      is dominant. Thus, disulfiram could directly interact with MMP-2 and MMP-9 and
      inhibit their proteolytic activity through a zincchelating mechanism. Addition of
      zinc could reverse the inhibition of invasiveness and collagenase inhibition
      through disulfiram treatment. This finding implies that MMP-2 and MMP-9 may be
      the inhibitory targets for a potential disulfiram treatment. These observations
      raise the possibility clinical therapeutic applications for disulfiram used as a
      potential inhibitor of metastatic cell invasion and angiogenesis.

PMID- 14573757
TI  - Interaction of G protein beta subunit with inward rectifier K(+) channel Kir3.
AB  - G protein betagamma subunits bind and activate G protein-coupled inward rectifier
      K+ (GIRK) channels. This protein-protein interaction is crucial for slow
      hyperpolarizations of cardiac myocytes and neurons. The crystal structure of
      Gbeta shows a seven-bladed propeller with four beta strands in each blade. The
      Gbeta/Galpha interacting surface contains sites for activating GIRK channels.
      Furthermore, our recent investigation using chimeras between Gbeta1 and yeast
      beta (STE4) suggested that the outer strands of blades 1 and 2 of Gbeta1 could be
      an interaction area between Gbeta1 and GIRK. In this study, we made point
      mutations on suspected residues on these outer strands and investigated their
      ability to activate GIRK1/GIRK2 channels. Mutations at Thr-86, Thr-87, and Gly
      131, all located on the loops between beta-strands, substantially reduced GIRK
      channel activation, suggesting that these residues are Gbeta/GIRK interaction
      sites. These mutations did not affect the expression of Gbeta1 or its ability to
      stimulate PLCbeta2. These residues are surface-accessible and located outside
      Gbeta/Galpha interaction sites. These results suggest that the residues on the
      outer surface of blades 1 and 2 are involved in the interaction of Gbetagamma
      with GIRK channels. Our study suggests a mechanism by which different effectors
      use different blades to achieve divergence of signaling. We also observed that
      substitution of alanine for Trp-332 of Gbeta1 impaired the functional interaction
      of Gbeta1 with GIRK, in agreement with the data on native neuronal GIRK channels.
      Trp-332 plays a critical role in the interaction of Gbeta1 with Galpha as well as
      all effectors so far tested.

PMID- 14573758
TI  - Interaction between the mu opioid receptor and filamin A is involved in receptor
      regulation and trafficking.
AB  - The carboxyl tail of the human mu opioid receptor was shown to bind the carboxyl
      terminal region of human filamin A, a protein known to couple membrane proteins
      to actin. Results from yeast two-hybrid screening were confirmed by direct
      protein-protein binding and by coimmunoprecipitation of filamin and mu opioid
      receptor from cell lysates. To investigate the role of filamin A in opioid
      receptor function and regulation, we used the melanoma cell line M2, which does
      not express filamin A, and its subclone A7, transfected with human filamin A
      cDNA. Both cell lines were stably transfected with cDNA encoding myc-tagged human
      mu opioid receptor. Fluorescent studies, using confocal microscopy, provided
      evidence that filamin and mu opioid receptors were extensively colocalized on the
      membranes of filamin-expressing melanoma cells. The immunostaining of mu opioid
      receptors indicated that the lack of filamin had no detectable effect on membrane
      localization of the receptors. Moreover, mu opioid receptors function normally in
      the absence of filamin A, as evidenced by studies of opioid binding and DAMGO
      inhibition of forskolin-stimulated adenylyl cyclase. However, agonist-induced
      receptor down-regulation and functional desensitization were virtually abolished
      in cells lacking filamin A. The level of internalized mu-opioid receptors, after
      30-min exposure to agonist, was greatly reduced, suggesting a role for filamin in
      mu opioid receptor trafficking. During these studies, we observed that forskolin
      activation of adenylyl cyclase was greatly reduced in filamin-lacking cells. An
      even more unexpected finding was the ability of long-term treatment with [d
      Ala2,N-Me-Phe4,Gly5-ol]-enkephalin of M2 cells, containing mu opioid receptors,
      to restore normal forskolin activation. The mechanism of this effect is currently
      unknown. It is postulated that the observed effects on mu opioid receptor
      regulation by filamin A and, by implication, of the actin cytoskeleton may be the
      result of its role in mu opioid receptor trafficking.

PMID- 14573759
TI  - Acquired cellular resistance to flavopiridol in a human colon carcinoma cell line
      involves up-regulation of the telomerase catalytic subunit and telomere
      elongation. Sensitivity of resistant cells to combination treatment with a
      telomerase inhibitor.
AB  - Flavopiridol is a broad-spectrum inhibitor of cyclin-dependent kinases and of
      global transcription via the inhibition of positive transcription elongation
      factor b (P-TEFb). Although flavopiridol is currently undergoing phase II
      clinical trials, acquired cellular resistance to the compound during treatment is
      a potential problem, as it is with almost all current anticancer agents. A HCT116
      human colon carcinoma cell line with an acquired 8-fold resistance to
      flavopiridol has been established. We report here that there are changes in these
      resistant cells in terms of telomere length and telomerase activity, whereas no
      change in the expression of the P-TEFb subunits CDK9, cyclin T1, cyclin T2a, or
      cyclin T2b was observed. The level of mRNA expression for the telomerase
      catalytic subunit hTERT was increased over 2-fold in the resistant cells, and
      mean telomere length was found to be 2 kb longer than the parental length,
      although telomerase activity was unchanged. The level of mRNA expression for the
      telomeric binding protein Pot1 was also increased. We also report that treatment
      of HCT116 cells with a combination of the G-quadruplex interacting telomerase
      inhibitor BRACO-19 and flavopiridol results in a 3-fold decrease in population
      doubling and prevents recovery from treatment with either compound alone.
      Treatment of flavopiridol-resistant cells with BRACO-19 alone also led to rapid
      inhibition of cell growth, which is not observed in the parental line. The
      finding that only the resistant line, with up-regulated telomerase, responds to
      this G-quadruplex inhibitor is consistent with the hypothesis that the mechanism
      of BRACO-19 down-regulation of cell growth directly involves the targeting of
      telomeres and telomerase.

PMID- 14573760
TI  - Role of mitochondrial aldehyde dehydrogenase in nitrate tolerance.
AB  - Glyceryl trinitrate (GTN) is used in the treatment of angina pectoris and cardiac
      failure, but the rapid onset of GTN tolerance limits its clinical utility.
      Research suggests that a principal cause of tolerance is inhibition of an enzyme
      responsible for the production of physiologically active concentrations of NO
      from GTN. This enzyme has not conclusively been identified. However, the
      mitochondrial aldehyde dehydrogenase (ALDH2) is inhibited in GTN-tolerant tissues
      and produces NO2- from GTN, which is proposed to be converted to NO within
      mitochondria. To investigate the role of this enzyme in GTN tolerance, cumulative
      GTN concentration-response curves were obtained for both GTN-tolerant and 
      nontolerant rat aortic rings treated with the ALDH inhibitor cyanamide or the
      ALDH substrate propionaldehyde. Tolerance to GTN was induced using both in vivo
      and in vitro protocols. The in vivo protocol resulted in almost complete
      inhibition of ALDH2 activity and GTN biotransformation in hepatic mitochondria,
      indicating that long-term GTN exposure results in inactivation of the enzyme.
      Treatment with cyanamide or propionaldehyde caused a dose-dependent increase in
      the EC50 value for GTN-induced relaxation of similar magnitude in both tolerant
      and nontolerant aorta, suggesting that although cyanamide and propionaldehyde
      inhibit GTN-induced vasodilation, these inhibitors do not affect the enzyme or
      system involved in tolerance development to GTN. Treatment with cyanamide or
      propionaldehyde did not significantly inhibit 1,1-diethyl-2-hydroxy-2
      nitrosohydrazine-mediated vasodilation in tolerant or nontolerant aorta,
      indicating that these ALDH inhibitors do not affect the downstream effectors of
      NO-induced vasodilation. Immunoblot analysis indicated that the majority of
      vascular ALDH2 is present in the cytoplasm, suggesting that mitochondrial
      biotransformation of GTN by ALDH2 plays a minor role in the overall vascular
      biotransformation of GTN by this enzyme.

PMID- 14573761
TI  - beta2-Adrenergic signaling in human heart: shift from the cyclic AMP to the
      arachidonic acid pathway.
AB  - We have recently established that enhancement of intracellular calcium cycling
      and contraction in response to beta2-adrenergic receptor (beta2-AR) stimulation
      exclusively relies on the activation of the cytosolic phospholipase A2 (cPLA2)
      and arachidonic acid production, via a pertussis toxin-sensitive G protein
      (possibly Gi), in embryonic chick cardiomyocytes. We aimed to investigate the
      relevance of the beta2-AR/Gi/cPLA2 pathway in the human myocardium. In left
      ventricular biopsies obtained from explanted hearts, beta2-AR stimulation exerted
      either an inhibition of cPLA2 that was insensitive to pertussis toxin (PTX)
      treatment, or an activation of cPLA2, sensitive to PTX treatment. In right atrial
      appendages from patients who were undergoing open heart surgery, we demonstrated
      that beta2-AR-induced activation of cPLA2 was favored in situations of altered
      beta1-AR and/or beta2-AR/adenylyl cyclase (AC) stimulations. Alterations were
      characterized by an increase in EC50value of norepinephrine and a decrease in the
      maximal AC activation in response to zinterol, respectively. Quantitative reverse
      transcription-polymerase chain reaction analyses highlighted a positive
      correlation between the expression of AC5 and AC6 mRNAs in human cardiac atria,
      which suggested that functional alterations in AC responses were unlikely to be
      related to changes in the AC5/AC6 mRNA ratio. In addition, the shift from the
      cyclic AMP to the arachidonic acid pathway was not supported at the
      transcriptional level by opposite regulation of AC and cPLA2mRNAs expression.
      This study gives the first evidence of the recruitment of cPLA2by beta2-ARs in
      the human heart and suggests that the Gi/cPLA2pathway could substitute for a
      deficient Gs/AC pathway in mediating beta2-AR responses.

PMID- 14573762
TI  - Up-regulation of alpha1B-adrenergic receptors with defects in G protein coupling:
      ligand-induced protection from receptor instability.
AB  - The biochemical basis for the unexpected agonist-induced up-regulation of the
      number of radioligand binding sites for two mutated alpha1B-adrenergic receptors
      reported previously was investigated. Up-regulation was independent of the
      expression vector used and was not prevented by cycloheximide or actinomycin D,
      eliminating several potential transcriptional mechanisms and new receptor protein
      synthesis. Antagonists were also able to induce up-regulation, suggesting that
      ligand occupancy without signal generation was sufficient to induce the increase
      in binding sites. Accordingly, we hypothesized that up-regulation results from
      ligand-induced protection from inherent instability of these mutated receptors.
      Studies with receptors in isolated membranes revealed that the two mutated
      receptors that exhibited up-regulation in intact cells also exhibited an inherent
      instability of their ligand binding capacity, and binding of either agonists or
      antagonists to these receptors could protect against the loss of binding. In
      contrast, the wild-type receptor and other mutated receptors that did not exhibit
      up-regulation in intact cells did not exhibit instability or ligand-induced
      protection in isolated membranes. The occurrence of instability and protection in
      isolated membranes for only those mutated receptors and ligands that exhibit up
      regulation in intact cells provides compelling evidence that the apparent up
      regulation of binding sites in intact cells results from ligand-induced
      protection from an inherent instability of these G protein coupling-defective
      receptors. Inclusion of protease inhibitors markedly reduced the loss of binding
      in isolated membranes, implicating membrane-localized proteolysis as the likely
      mechanism for the instability.

PMID- 14573763
TI  - Effect of glutathione depletion on sites and topology of superoxide and hydrogen
      peroxide production in mitochondria.
AB  - In this work, the topology of mitochondrial O2(-)(radical) and H2O2 generation
      and their interplay with matrix GSH in isolated heart mitochondria were examined.
      We observed that complex I releases O2(-)(radical) into the matrix (where it is
      converted to H2O2 by Mn-SOD) but not into the intermembrane space. No free
      radical generation was observed from complex II, but succinate treatment caused
      H2O2 generation from the matrix through a reverse electron flow to complex I.
      Complex III was found to release O2(-)(radical) into the matrix and into the
      intermembrane space. Antimycin, which increases steady-state levels of UQO>-
      (ubisemiquinone at the Qo site) in complex III, enhanced both H2O2 generation
      from the matrix and O2(-)(radical) production from the intermembrane space. On
      the other hand, myxothiazol, which inhibits UQO>- formation, completely inhibited
      antimycin induced O2(-)(radical) toward the intermembrane space and inhibited
      H2O2 generation from the matrix by 70%. However, myxothiazol alone enhanced H2O2
      production from complex III, suggesting that other components of complex III
      besides the UQO- can cause O2(-)(radical) generation toward the matrix. As
      expected, mitochondrial GSH was found to modulate H2O2 production from the matrix
      but not O2- generation from the intermembrane space. Low levels of GSH depletion
      (from 0-40%, depending on the rate of H2O2 production) had no effect on H2O2
      diffusion from mitochondria. Once this GSH depletion threshold was reached, GSH
      loss corresponded to a linear increase in H2O2 production by mitochondria. The
      impact of 50% mitochondrial GSH depletion, as seen in certain pathological
      conditions in vivo, on H2O2 production by mitochondria depends on the metabolic
      state of mitochondria, which governs its rate of H2O2 production. The greater the
      rate of H2O2 generation the greater the effect 50% GSH depletion had on enhancing
      H2O2 production.

PMID- 14573764
TI  - An N-terminal histidine is the primary determinant of alpha subunit-dependent
      Cu2+ sensitivity of alphabeta3gamma2L GABA(A) receptors.
AB  - Copper (Cu2+) is a physiologically important cation and is released from nerve
      terminals. Cu2+ modulates GABAA receptor currents in an alpha subunit subtype
      dependent manner; alpha1beta3gamma2L receptors are more sensitive to Cu2+ than
      alpha6beta3gamma2L receptors. We compared the effect of Cu2+ on alphabeta3gamma2L
      receptors containing each of the six alpha subtypes and generated alpha1/alpha6
      chimeras and mutants to determine the functional domain(s) and specific residues
      responsible for alpha subtype-dependent differences in Cu2+ sensitivity. Whole
      cell GABAA receptor currents were obtained from L929 fibroblasts coexpressing
      wild-type, chimeric and mutant alpha subunits with beta3 and gamma2L subunits.
      Maximal Cu2+ inhibition of alpha1beta3gamma2L and alpha2beta3gamma2L receptor
      currents was larger (52.2 +/- 3.0 and 59.0 +/- 2.5%, respectively) than maximal
      inhibition of alpha3beta3gamma2L, alpha4beta3gamma2L, alpha5beta3gamma2L, and
      alpha6beta3gamma2L receptor currents (22.6 +/- 3.1, 19.2 +/- 3.4, 20.2 +/- 4.8,
      and 21.2 +/- 3.6%, respectively). Receptors containing chimeric constructs with
      alpha1 subtype N-terminal sequence between residues 127 and 232 were inhibited by
      Cu2+ to an extent similar to those with alpha1 subtypes, suggesting that this N
      terminal region (127-232) contains a major determinant for high Cu2+ sensitivity.
      alpha1 subtype residues V134, R135, and H141 in a VRAECPMH motif (VQAECPMH in the
      alpha2 subtype) conferred higher Cu2+ sensitivity, and the H141 residue was the
      major determinant in the motif. The beta3 subtype M2 domain residue H267, which
      is a major determinant of Zn2+ inhibition, and alpha6 subtype M2-M3 loop residue
      H273, which is responsible for the increased Zn2+ sensitivity of the alpha6
      subtype, also seemed to contribute to Cu2+ inhibition. These data suggest that
      the N-terminal VR(Q)AECPMH motif in alpha1 and alpha2 subtypes is the major
      determinant of increased subtype-dependent inhibition by Cu2+, that residue H141
      is the major determinant in that motif, and that Cu2+ may also interact with
      GABAA receptors at sites similar to or overlapping Zn2+ sites.

PMID- 14573765
TI  - Small interfering RNA suppression of polyamine analog-induced spermidine/spermine
      n1-acetyltransferase.
AB  - N1,N11-diethylnorspermine (DENSPM) is a polyamine analog that down-regulates
      polyamine biosynthesis and potently upregulates the polyamine catabolic enzyme
      spermidine/spermine N1-acetyltransferase (SSAT). In certain cells, such as SKMEL
      28 human melanoma cells, induction of SSAT is associated with rapid apoptosis. In
      this study, we used small interfering RNA (siRNA) to examine the role of SSAT
      induction in mediating polyamine pool depletion and apoptosis. siRNA duplexes
      were designed to target three independent sites in the SSAT mRNA coding region
      (siSSAT). When transfected under nontoxic conditions, two of the duplexes
      selectively reduced basal SSAT mRNA in HEK-293 cells by >80% and prevented DENSPM
      induced SSAT mRNA by 95% in SK-MEL-28 cells. Treatment of SK-MEL-28 cells with 10
      muM DENSPM in the presence of 83 nM siSSAT selectively prevented the 1400-fold
      induction of SSAT activity by approximately 90% and, in turn, prevented analog
      depletion of spermine (Spm) pools by approximately 35%. siSSAT also prevented
      DENSPM-induced cytochrome c release and caspase-3 cleavage at 36 h and apoptosis
      at 48 h as measured by annexin V staining. Overall, the data directly link analog
      induction of SSAT to Spm pool depletion and to caspase-dependent apoptosis in
      DENSPM-treated SK-MEL-28 cells. This represents the first use of siRNA technology
      directed toward a polyamine gene and the first unequivocal demonstration that
      SSAT induction initiates events leading to polyamine analog-induced apoptosis.

PMID- 14573766
TI  - The peptide KLVFF-K(6) promotes beta-amyloid(1-40) protofibril growth by
      association but does not alter protofibril effects on cellular reduction of 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT).
AB  - The peptide KLVFF-K6 was observed by Lowe et al. to simultaneously enhance
      amyloid beta-protein (Abeta) fibrillogenesis and decrease cellular toxicity, as
      measured in a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)
      reduction assay. It was postulated that accelerated Abeta aggregation and
      precipitation induced by KLVFF-K6 may lead to an increase in less toxic insoluble
      fibrils at the expense of more toxic soluble protofibrils. In a previous study,
      we distinguished between two modes of protofibril growth: elongation by monomer
      deposition and direct protofibril-protofibril association. These growth
      mechanisms could be resolved by varying Abeta monomer and NaCl concentrations.
      Using assays designed to isolate these distinct modes of protofibril growth, we
      report here that larger Abeta aggregates formed in the presence of KLVFF-K6
      resulted from enhanced protofibril association. 3H-Radiomethylated KLVFF-K6 bound
      to associated protofibrils with an apparent Kd of 180 nM, and concentrations of
      free [3H]KLVFF-K6 in this range were sufficient to convert soluble protofibrils
      to sedimentable fibrils. However, promotion of Abeta protofibril association by
      KLVFF-K6 had no effect on Abeta-induced decreases in cellular MTT reduction.
      Therefore, our data do not support the proposal that insoluble fibrils formed
      with KLVFF-K6 are less toxic than soluble protofibrils. KLVFF-K6 did not alter
      rates of protofibril elongation by monomer deposition. In contrast, when added to
      Abeta monomers isolated with the use of size-exclusion chromatography, KLVFF-K6
      inhibited fibrillogenesis, as measured by thioflavin T fluorescence, and this
      inhibition was paralleled by a failure to alter cellular MTT reduction.

PMID- 14573767
TI  - Inhibition of interleukin-4 production in CD4+ T cells by peroxisome proliferator
      activated receptor-gamma (PPAR-gamma) ligands: involvement of physical
      association between PPAR-gamma and the nuclear factor of activated T cells
      transcription factor.
AB  - Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) has been implicated
      in the regulation of multiple inflammatory processes. However, little is known of
      PPAR-gamma in the regulation of interleukin (IL)-4 expression in T cells. In this
      study, the effects of PPAR-gamma ligands on production of IL-4, a pro
      inflammatory cytokine associated with the pathophysiology of allergic diseases,
      were investigated. 15-Deoxy-Delta12,14 prostaglandin J2 (15d-PGJ2) and
      ciglitazone, two representative PPAR-gamma ligands, significantly inhibited IL-4
      production in both antigen-stimulated primary CD4+ T cells and the phorbol 12
      myristate 13-acetate (PMA)/ionomycin-activated EL-4 T cell line. 15d-PGJ2 and
      ciglitazone inhibited the activation of IL-4 gene promoter in EL-4 T cells
      transiently transfected with IL-4 promoter/reporter constructs, and the
      repressive effect mapped to a region in the IL-4 promoter containing binding
      sites for nuclear factor of activated T cells (NF-AT). The activation of T cells
      by PMA/ionomycin resulted in a marked enhancement of the binding activities to
      the NF-AT site that was significantly inhibited by the addition of PPAR-gamma
      ligands. In cotransfected EL-4 T cells, PPAR-gamma also inhibited the activation
      of the IL-4 promoter at multiple NF-AT sites in a ligand-dependent manner. NF
      ATc1 bound PPAR-gamma both in vivo and in vitro, and the interaction interfaces
      involved the Rel similarity domain of NF-ATc1. In cotransfections of HeLa cells,
      PPAR-gamma inhibited the NF-ATc1 transactivation in a ligand-dependent manner.
      Coexpression of p300 or AP-1 relieved the PPAR-gamma ligand-mediated inhibition
      of the NF-AT transactivation. From these results, we propose that PPAR-gamma
      ligand-mediated suppression of IL-4 production in CD4+ T cells may involve both
      inhibition of the NFAT-DNA interactions and competitive recruitment of
      transcription integrators between NF-AT and PPAR-gamma.

PMID- 14573768
TI  - Regulation of the rat phenylethanolamine N-methyltransferase gene by
      transcription factors Sp1 and MAZ.
AB  - The rat phenylethanolamine N-methyltransferase (PNMT) gene promoter contains 1
      base pair (bp) overlapping consensus sequences for Sp1 and MAZ transcription
      factors at -48 and -38 bp, respectively. Gel mobility assays using PC-12-derived
      RS1 cell nuclear extracts or in vitro translated proteins showed that Sp1 and MAZ
      specifically bind to these elements, that MAZ displaces/prevents Sp1 binding, and
      that Sp1 and MAZ binding is mutually exclusive, with occupancy dependent on each
      factor's concentration and affinity for its consensus element. In transfection
      assays, PNMT promoter activation by Sp1 and MAZ depends on promoter length, with 
      893 bp of sequence yielding greatest activation. Although MAZ has higher affinity
      for its binding element, it is a less effective activator. Changes in PNMT
      promoter activity for the constructs pGL3RP60 or pGL3RP893 using a fixed amount
      of MAZ expression construct and a variable amount of Sp1 expression construct or
      vice versa confirmed the latter. Mutation of the MAZ or Sp1 sites in pGL3RP60
      attenuated but did not eliminate PNMT promoter activity, even though the proteins
      no longer bind to their consensus elements. Phosphatase treatment of RS1 cell
      nuclear extracts prevented MAZ- and Sp1-DNA binding complex formation. Although
      MAZ and Sp1 elevate endogenous PNMT mRNA in RS1 cells, MAZ preferentially
      increases intron-retaining whereas Sp1 preferentially increases intronless mRNA.
      Thus, expression of the PNMT gene seems to be modulated through competitive
      binding of phosphorylated Sp1 and MAZ to their consensus elements in the
      promoter. In addition, post-transcriptional regulation seems to be another
      important mechanism controlling PNMT expression.

PMID- 14573769
TI  - Ceramide is involved in r(+)-methanandamide-induced cyclooxygenase-2 expression
      in human neuroglioma cells.
AB  - Cannabinoids have recently been shown to induce the expression of the
      cyclooxygenase-2 (COX-2) isoenzyme in H4 human neuroglioma cells. Using this cell
      line, the present study investigates the contribution of the second messenger
      ceramide to this signaling pathway. Incubation of cells with the endocannabinoid
      analog R(+)-methanandamide (R(+)-MA) was associated with an increase of
      intracellular ceramide levels. Enhancement of ceramide formation by R(+)-MA was
      abolished by fumonisin B1, a ceramide synthase inhibitor, whereas inhibitors of
      neutral sphingomyelinase (spiroepoxide, glutathione) and serine
      palmitoyltransferase (l-cycloserine, ISP-1) were inactive in this respect. R(+)
      MA caused a biphasic activation of the p38 and p42/44 mitogen-activated protein
      kinases (MAPKs), with phosphorylation peaks occurring after 15-min and 4- to 8-h
      treatments, respectively. Inhibition of ceramide synthesis with fumonisin B1 was
      associated with a suppression of R(+)-MA-induced delayed phosphorylations of p38
      and p42/44 MAPKs and subsequent COX-2 expression. The involvement of ceramide in
      COX-2 expression was corroborated by findings showing that C2-ceramide and
      neutral sphingomyelinase from Bacillus cereus caused concentration-dependent
      increases of COX-2 expression that were suppressed in the presence of 4-(4
      fluorophenyl)-2-(4-methylsulfonylphenyl)-5-(4-pyridyl)imidazol (SB203580, a p38
      MAPK inhibitor) or 2'-amino-3'-methoxyflavone (PD98059, a p42/44 MAPK activation
      inhibitor). In contrast, dihydro-C2-ceramide being used as a negative control did
      not induce MAPK phosphorylation and COX-2 expression. Collectively, our results
      demonstrate that R(+)-MA induces COX-2 expression in human neuroglioma cells via
      synthesis of ceramide and subsequent activation of p38 and p42/44 MAPK pathways.
      Induction of COX-2 expression via ceramide represents a hitherto unknown
      mechanism by which cannabinoids mediate biological effects within the central
      nervous system.

PMID- 14573770
TI  - Common signaling pathways link activation of murine PAR-1, LPA, and S1P receptors
      to proliferation of astrocytes.
AB  - Receptors for the serine protease thrombin and for lysophospholipids are coupled
      to G proteins and control a wide range of cellular functions, including
      mitogenesis. Activators of these receptors are present in blood, and can enter
      the brain during central nervous system (CNS) injury. Reactive astrogliosis, a
      prominent component of CNS injury with potentially harmful consequences, may
      involve proliferation of astrocytes. In this study, we have examined the
      expression and activation of protease activated receptors (PARs),
      lysophosphatidic acid (LPA) receptors, and sphingosine-1-phosphate (S1P)
      receptors on murine astrocytes. We show that activation of these three receptor
      classes can lead to astrogliosis in vivo and proliferation of astrocytes in
      vitro. Cultured murine cortical astrocytes express mRNA for multiple receptor
      subtypes of PAR (PAR-1-4), LPA (LPA-1-3) and S1P (S1P-1, -3, -4, and -5)
      receptors. Comparison of the intracellular signaling pathways of glial PAR-1,
      LPA, and S1P receptors indicates that each receptor class activates multiple
      downstream signaling pathways, including Gq/11-directed inositol lipid/Ca2+
      signaling, Gi/o activation of mitogen-activated protein kinases (MAPK)
      (extracellular signal-regulated kinase 1/2 and stress activated protein kinase/c
      jun N-terminal kinase, but not p38), and activation of Rho pathways. Furthermore,
      activation of these different receptor classes can differentially regulate two
      transcription factor pathways, serum response element and nuclear factor of
      activated T cells. Blockade of Gi/o signaling with pertussis toxin, MAPK
      activation with 1,4-diamino-2,3-dicyano-1,4-bis(2-aminophynyltio)butadiene
      (U0126), or Rho kinase signaling with R-(+)-trans-N-(4-pyridyl)-4-(1-aminoethyl)
      cyclohexane carboxamide (Y27632) can markedly reduce the proliferative response
      of glial cells to PAR-1, LPA, or S1P receptor activation, suggesting that each of
      these pathways is important in coupling of receptor activation to glial
      proliferation.

PMID- 14573771
TI  - Purification and functional reconstitution of the human P2Y12 receptor.
AB  - The human P2Y12 receptor (P2Y12-R) is a member of the G protein coupled P2Y
      receptor family, which is intimately involved in platelet physiology. We describe
      here the purification and functional characterization of recombinant P2Y12-R
      after high-level expression from a baculovirus in Sf9 insect cells. Purified
      P2Y12-R, Gbeta1gamma2, and various Galpha-subunits were reconstituted in lipid
      vesicles, and steady-state GTPase activity was quantified. GTP hydrolysis in
      proteoliposomes formed with purified P2Y12-R and Galphai2beta1gamma2 was
      stimulated by addition of either 2-methylthio-ADP (2MeSADP) or RGS4 and was
      markedly enhanced by their combined presence. 2MeSADP was the most potent agonist
      (EC50 = 80 nM) examined, whereas ADP, the cognate agonist of the P2Y12-R, was 3
      orders of magnitude less potent. ATP had no effect alone but inhibited the action
      of 2MeSADP; therefore, ATP is a relatively low-affinity antagonist of the P2Y12
      R. The G protein selectivity of the P2Y12-R was examined by reconstitution with
      various G protein alpha-subunits in heterotrimeric form with Gbeta1gamma2. The
      most robust coupling of the P2Y12-R was to Galphai2, but effective coupling also
      occurred to Galphai1 and Galphai3. In contrast, little or no coupling occurred to
      Galphao or Galphaq. These results illustrate that the signaling properties of the
      P2Y12-R can be studied as a purified protein under conditions that circumvent the
      complications that occur in vivo because of nucleotide metabolism and
      interconversion as well as nucleotide release.

PMID- 14573772
TI  - The allosteric potentiation of nicotinic acetylcholine receptors by galantamine
      is transduced into cellular responses in neurons: Ca2+ signals and
      neurotransmitter release.
AB  - Neuronal nicotinic acetylcholine receptors (nAChR) modulate a variety of cellular
      responses, including Ca2+ signals and neurotransmitter release, which can
      influence neuronal processes such as synaptic efficacy and neuroprotection. In
      addition to receptor activation through the agonist binding site, an allosteric
      modulation of nAChR has also been described for a novel class of allosteric
      ligands. Of these, the acetylcholinesterase inhibitor and Alzheimer drug
      galantamine represents the prototypical allosteric ligand, based on its
      potentiation of nAChR-evoked single-channel and whole-cell currents. The aim of
      this study was to establish whether the allosteric potentiation of nAChR currents
      is transduced in downstream cellular responses to nAChR activation, namely
      increases in intracellular Ca2+ and [3H]noradrenaline release. In SH-SY5Y cells,
      galantamine potentiated nicotine-evoked increases in intracellular Ca2+ and
      [3H]noradrenaline release with a bell-shaped concentration-response profile;
      maximum enhancement of nicotine-evoked responses occurred at 1 muM galantamine.
      This potentiation was blocked by mecamylamine, whereas galantamine had no effect
      on these measures in the absence of nicotine. Galantamine did not compete for
      radioligand binding to the agonist binding sites of several nAChR subtypes,
      consistent with an allosteric mode of action. Unlike galantamine, the
      acetylcholinesterase inhibitors rivastigmine and donepezil did not potentiate
      nAChR-mediated responses, whereas donepezil was a reasonably potent inhibitor of
      nicotine- and KCl-evoked increases in Ca2+. nAChR-mediated [3H]noradrenaline
      release from hippocampal slices was also potentiated by galantamine, with an
      additional component attributable to acetylcholinesterase inhibition and
      subsequent increase in acetylcholine. These results indicate that the allosteric
      regulation of nAChR results in the potentiation of receptor-dependent cellular
      processes relevant to many of the physiological consequences of nAChR activation.

PMID- 14573773
TI  - Ligand-receptor-G-protein molecular assemblies on beads for mechanistic studies
      and screening by flow cytometry.
AB  - G protein-coupled receptors form a ternary complex of ligand, receptor, and G
      protein heterotrimer (LRG) during signal transduction from the outside to the
      inside of a cell. Our goal was to develop a homogeneous, small-volume, bead-based
      approach compatible with high-throughput flow cytometry that would allow
      evaluation of G protein coupled receptor molecular assemblies. Dextran beads were
      derivatized to carry chelated nickel to bind hexahistidine-tagged green
      fluorescent protein (GFP) and hexahistidine-tagged G proteins. Ternary complexes
      were assembled on these beads using fluorescent ligand with wild-type receptor or
      a receptor-Gialpha2 fusion protein, and with a nonfluorescent ligand and receptor
      GFP fusion protein. Streptavidin-coated polystyrene beads used biotinylated anti
      FLAG antibodies to bind FLAG-tagged G proteins for ternary complex assembly.
      Validation was achieved by showing time and concentration dependence of ternary
      complex formation. Affinity measurements of ligand for receptor on particles, of
      the ligand-receptor complex for G protein on the particles, and receptor-Gialpha2
      fusion protein for Gbetagamma, were consistent with comparable assemblies in
      detergent suspension. Performance was assessed in applications representing the
      potential of these assemblies for ternary complex mechanisms. We showed the
      relationship for a family of ligands between LR and LRG affinity and
      characterized the affinity of both the wild-type and GFP fusion receptors with G
      protein. We also showed the potential of kinetic measurements to allow
      observation of individual steps of GTP-induced ternary complex disassembly and
      discriminated a fast step caused by RG disassembly compared with the slower step
      of Galphabetagamma disassembly.

PMID- 14573774
TI  - Selective interaction of ARF1 with the carboxy-terminal tail domain of the 5-HT2A
      receptor.
AB  - The 5-hydroxytryptamine 2A receptor (5-HT2AR) is a member of the class I family
      of rhodopsin-related G protein-coupled receptors. The receptor is known to
      activate phospholipase C via the heterotrimeric G proteins Gq/11, but we showed
      previously that it can also signal through the phospholipase D (PLD) pathway in
      an ADP-ribosylation factor (ARF)-dependent manner that seems to be independent of
      Gq/11 (Mitchell et al., 1998). Both coimmunoprecipitation experiments and the
      effects of negative mutant ARF constructs on 5-HT2AR-induced PLD activation here
      suggested that ARF1 may play a greater role than ARF6 in the function of this
      receptor. Furthermore, we demonstrated using glutathione S-transferase (GST)
      fusion proteins of receptor domains that ARF1 and ARF6 bind to the third
      intracellular loop (i3) and the carboxy terminal tail (ct) of the 5-HT2AR. The
      association of ARF1 with the ct domain of the receptor was stronger than its
      interaction with i3, or the interactions of ARF6 with either construct.
      Experiments using ARF mutants that are deficient in GTP loading, and the in vitro
      addition of GTPgammaS suggested that GTP loading enhances ARF1 binding to the
      receptor. The N376PxxY motif in the transmembrane 7 domain of the receptor
      (rather than a N376DPxxY mutant form) was shown to be essential for ARF-dependent
      PLD signaling and ARF1 coimmunoprecipitation. In GST-fusion proteins of the 5
      HT2AR ct domain, mutation of Asn376 to Asp also markedly reduced ARF1-HA binding,
      although additional motifs in the Asn376-Asn384 sequence and to a lesser extent
      elsewhere, seem also to contribute to the interaction.

PMID- 14573775
TI  - Expression of the angiogenic factor thymidine phosphorylase in THP-1 monocytes:
      induction by autocrine tumor necrosis factor-alpha and inhibition by aspirin.
AB  - The angiogenic factor thymidine phosphorylase (TP) is highly expressed in human
      monocytes and macrophages, and its expression has been linked to the pathology
      and progression of solid tumors, rheumatoid arthritis, and gastric ulcers. In
      this study, TP mRNA and enzyme activity were found to be up-regulated upon the
      induction of differentiation of the human monocyte cell line THP-1 by phorbol 12
      myristate 13-acetate (PMA). TP expression in THP-1 cells was similarly increased
      by tumor necrosis factor-alpha (TNFalpha). Because monocytes and macrophages are
      a predominant source of TNFalpha, the up-regulation of TP upon THP-1
      differentiation could have been caused by the autocrine production of TNFalpha.
      In support of this hypothesis, PMA increased TNFalpha mRNA levels; furthermore,
      the increase in TP expression with PMA treatment was partially blocked by a
      neutralizing antibody to TNFalpha, particularly at the earlier time points. This
      data also suggested there may be additional mechanisms regulating TP expression
      upon PMA treatment of the cells. The induction of TP by TNFalpha was mimicked by
      an antibody to the TNFalpha receptor R2 (TNF-R2; p75), but not by an antibody to
      TNF-R1 (p55), suggesting that the TNF-R2 plays a role in the regulation of TP
      expression. The PMA-induced increase in TP expression was blocked by aspirin but
      not by the related agent indomethacin, suggesting that aspirin's effect was not
      caused by the inhibition of cellular cyclooxygenases. An alternative mechanism by
      which aspirin inhibits gene expression is the modulation of the transcription
      factor NFkappaB, and the TNFalpha-induced increase in TP mRNA was blocked by a
      cell-permeable NFkappaB inhibitory peptide. Furthermore, TNFalpha increased and
      aspirin (but not indomethacin) decreased NFkappaB DNA-binding activity in THP-1
      cells. In conclusion, the modulation of TP expression in monocytes by pro- and
      anti-inflammatory agents suggests that its angiogenic-related actions could
      contribute to the inflammatory response associated with a number of
      pathophysiological conditions.

PMID- 14573776
TI  - Cloning and Characterization of the Murine and Rat mrp1 Promoter Regions.
AB  - The ATP-binding cassette transporter multidrug resistance protein 1 (MRP1)
      confers resistance to a number of clinically important chemotherapeutic agents.
      The proximal promoter region of MRP1 is GC-rich and contains binding sites for
      members of the Sp1 family of trans-acting factors that seem to be important for
      basal expression. As an approach to searching for other elements that may
      contribute to expression, we have sequenced and functionally compared the
      promoters of the murine and rat mrp1 genes with that of the human gene. All three
      promoters are GC-rich, TATA-less, and CAAT-less. Conservation of sequence between
      rodent and human promoters is limited to a proximal region of 100 nucleotides
      containing binding sites for members of the Sp1 family and a putative activator
      protein-1 element. The 5'-untranslated region (UTR) of human MRP1 contains an
      insertion of approximately 160 nucleotides comprising a GCC-triplet repeat and a
      GC-rich tandem repeat that is absent from the rodent sequences. Transient
      transfection analyses demonstrated that the conserved GC-boxes of all three genes
      are the major determinants of basal activity. Based on electrophoretic mobility
      shift assays, each GC-box can be bound by Sp1 or Sp3. Unlike the rodent genes,
      the human MRP1 5'UTR also binds Sp1 but not Sp3, and the human promoter retains
      substantial activity even in the absence of the conserved GC-boxes. Finally, we
      show that the tumor suppressor protein p53 can repress the human and rodent
      promoters by a mechanism that is independent of the Sp1 elements.

PMID- 14573778
TI  - Quest for controls in molecular genetics.

PMID- 14573777
TI  - Techniques and pitfalls in the detection of pathogenic mitochondrial DNA
      mutations.
AB  - Mutations in the mitochondrial DNA (mtDNA) are now recognized as major
      contributors to human pathologies and possibly to normal aging. A large number of
      rearrangements and point mutations in protein coding and tRNA genes have been
      identified in patients with mitochondrial disorders. In this review, we discuss
      genotype-phenotype correlations in mitochondrial diseases and common techniques
      used to identify pathogenic mtDNA mutations in human tissues. Although most of
      these approaches employ standard molecular biology tools, the co-existence of
      wild-type and mutated mtDNA (mtDNA heteroplasmy) in diseased tissues complicates
      both the detection and accurate determination of the size of the mutated
      fractions. To address these problems, novel approaches were developed and are
      discussed in this review.

PMID- 14573779
TI  - Gene expression profiling during all-trans retinoic acid-induced cell
      differentiation of acute promyelocytic leukemia cells.
AB  - Using cDNA microarrays we determined the gene expression patterns in the human
      acute promyelocytic leukemia (APL) cell line NB4 during all-trans retinoic acid
      (ATRA)-induced differentiation. We analyzed the expression of 12,288 genes in the
      NB4 cells after 12 hours, 24 hours, 48 hours, 72 hours, and 96 hours of ATRA
      exposure. During this time course, we found 168 up-regulated and more than 179
      down-regulated genes, most of which have not been reported before. Many of the
      altered genes encode products that participate in signaling pathways, cell
      differentiation, programmed cell death, transcription regulation, and production
      of cytokines and chemokines. Of interest, the CD52 and protein kinase A
      regulatory subunit alpha (PKA-Rlalpha) genes, whose products are being used as
      therapeutic targets for certain human neoplasias in currently ongoing clinical
      trials, were among the genes observed to be markedly up-regulated after ATRA
      treatment. The present study provides valuable data to further understand the
      mechanism of ATRA-induced APL cell differentiation and suggests potential
      therapeutic alternatives for this leukemia.

PMID- 14573780
TI  - A single nucleotide primer extension assay to detect the APC I1307K gene variant.
AB  - Adenomatous polyposis coli (APC) is a tumor suppressor gene important in
      colorectal tumorigenesis. A genetic variant of APC, I1307K, results from a T-to-A
      transversion at nucleotide 3920 which converts the wild-type sequence to a
      homopolymer tract (A(8)). The I1307K alteration is not itself oncogenic, but
      creates a hypermutable region (A(8)) that is prone to frame-shift mutations. The
      APC I1307K variant occurs in approximately 6% of the Ashkenazi Jewish population
      and is reported to approximately double an individual's risk for colorectal
      cancer. Here we describe a single nucleotide primer extension assay for the
      detection of the APC I1307K mutation. Following PCR amplification, nucleotide
      3920 of the APC gene is directly sequenced using single nucleotide primer
      extension technology. The assay is in a multiplex format allowing simultaneous
      forward and reverse sequencing of the I1307K variant, which provides an internal,
      independent confirmation of each testing result. The assay was validated against
      60 samples previously characterized by an allele-specific oligonucleotide (ASO)
      hybridization assay, with 100% concordance of results. Compared to the ASO assay,
      this single nucleotide primer extension assay requires significantly less
      technical time to perform, and has a greatly increased throughput capacity. The
      single nucleotide extension assay provides a highly sensitive and specific assay
      to identify individuals with the APC I1307K gene variant who may benefit from
      increased colorectal screening.

PMID- 14573781
TI  - Establishment of stably EBV-transformed cell lines from residual clinical blood
      samples for use in performance evaluation and quality assurance in molecular
      genetic testing.
AB  - Positive control materials for clinical molecular genetic testing applications
      are currently in critically short supply or non-existent for many genetically
      based diseases of public health importance. Here we demonstrate that anonymous,
      residual, clinical blood samples are potential sources of viable lymphocytes for
      establishing Epstein-Barr virus (EBV)-transformed blood lymphocyte cell lines. We
      attempted to transform 34 residual blood samples, and analyzed transformation
      success with respect to sample age, anticoagulant, storage temperature, volume,
      hemolysis, and patient age and sex. In univariate analysis, sample age was
      significantly associated with transformation success (P = 0.002). The success
      rate was 67% (6 of 9) for samples 1 to 7 days old, 38% (3 of 8) for samples 8 to
      14 days old and 0% for samples 15 to 21 (0 of 11) days old. When we controlled
      for sample age in multivariate logistic regression, anticoagulant and storage
      temperature approached significance (P = 0.070 and 0.087, respectively; samples
      in acid citrate dextrose (ACD) and refrigerated samples were more likely to
      transform). Based on these findings, we suggest that samples collected in either
      ACD or ethylene diamine tetraacetic acid, and up to 14 days old (refrigerated) or
      7 days old (stored ambient), are reasonable candidates for EBV transformation.
      The transformation rate for samples that met these criteria was 63% (10 of 16).
      Implementation of this process could help alleviate the shortage of positive
      control materials for clinical molecular genetic testing.

PMID- 14573782
TI  - Multiplex RT-PCR for the detection of leukemia-associated translocations:
      validation and application to routine molecular diagnostic practice.
AB  - The aim of this study was to validate the application of a commercially available
      multiplex reverse transcription polymerase chain reaction (RT-PCR) assay
      [Hemavision-7 System] for the seven most common leukemia translocations for
      routine molecular diagnostic hematopathology practice. A total of 98 samples,
      comprising four groups, were evaluated: Group 1, 16 diagnostic samples
      molecularly positive by our existing laboratory-developed assays for PML
      RARalpha/t (15;17) or BCR-ABL/t (9;22); Group 2, 51 diagnostic samples negative
      by our laboratory-developed assays for PML-RARalpha/t (15;17) or BCR-ABL/t
      (9;22); Group 3, 21 prospectively analyzed diagnostic cases, without prior
      molecular studies; and Group 4, 10 minimal residual disease (MRD) samples.
      Analysis of the two previously studied cohorts (Groups 1 and 2) confirmed the
      diagnostic sensitivity and specificity of the multiplex assay with regard to
      these two translocations. Additionally, however, in the "negative" Group (Group
      2) the assay revealed three unanticipated translocations (CBFbeta-MYH11, BCR-ABL,
      and MLL-AF4), two of which were confirmed on cytogenetics. Analysis of the
      prospective cohort demonstrated that the assay was cost-effective and amenable to
      standard laboratory practice, with an identically sensitive MRD detection rate to
      that of our laboratory-developed tests. Virtually all of the results obtained
      were consistent with the phenotype and karyotype by conventional methods. This
      study illustrates the utility of a kit-based multiplex RT-PCR assay for the
      molecular diagnosis and monitoring of leukemias and reinforces the complementary
      roles of molecular testing and cytogenetics in diagnostic hematopathology.

PMID- 14573784
TI  - Comparison of GenFlex Tag array and Pyrosequencing in SNP genotyping.
AB  - With the completion of the Human Genome Project, over 2 million sequence-verified
      single nucleotide polymorphisms (SNPs) have been deposited in public databases.
      The challenge has shifted from SNP identification to high-throughput SNP
      genotyping. Although this has had little impact on molecular diagnostics, it
      provides the potential for future molecular diagnostics of complex traits to
      include SNP profiling. Accordingly, efficient, accurate, and flexible SNP
      genotyping are needed. In addition, the drive for low cost has pushed genotyping
      reactions toward multiplexing capability. We compared two SNP genotyping
      techniques: Affymetrix GenFlex Tag array and Pyrosequencing. The reference method
      was a well-established, solid-phase, single nucleotide extension reaction
      technique based on tritium detection. Fourteen SNPs were selected from the fine
      mapping project of a multiple sclerosis locus on chromosome 17q. Using all three
      techniques and the reference method, the SNPs were analyzed in 96 related
      individuals. Without extensive optimization, we successfully genotyped 11 of 14
      SNPs with both GenFlex and Pyrosequencing. Our study suggests that the
      Pyrosequencing technique provides higher accuracy between the two systems which
      is most likely due to the single-stranded template in the extension reaction.
      Thus, Pyrosequencing has potential for diagnostic applications. Pyrosequencing,
      however, is not optimal for large SNP profiling analyses wherein multiplexing
      potential is an advantage.

PMID- 14573783
TI  - Lunx is a superior molecular marker for detection of non-small cell lung cancer
      in peripheral blood [corrected].
AB  - The clinical management of non-small cell lung cancer (NSCLC) would benefit
      greatly by a test that was able to detect small amounts of NSCLC in the
      peripheral blood. In this report, we used a novel strategy to enrich tumor cells
      from the peripheral blood of 24 stage I to IV NSCLC patients and determined
      expression levels for six cancer-associated genes (lunx, muc1, KS1/4, CEA, CK19,
      and PSE). Using thresholds established at three standard deviations above the
      mean observed in 15 normal controls, we observed that lunx (10 of 24, 42%), muc1
      (5 of 24, 21%), and CK19 (5 of 24, 21%) were overexpressed in 14 of 24 (58%)
      peripheral blood samples obtained from NSCLC patients. Patients who overexpressed
      either KS1/4 (n = 2) or PSE (n = 1) also overexpressed either lunx or muc1. Of
      patients with presumed curable and resectable stage I to II disease (n = 7), at
      least one marker was overexpressed in three (43%) patients. In advanced stage III
      to IV patients (n = 17), at least one marker was overexpressed in 11 patients
      (65%). These results provide evidence that circulating tumor cells can be
      detected in NSCLC patients by a high throughput molecular technique. Further
      studies are needed to determine the clinical relevance of gene overexpression.

PMID- 14573785
TI  - Prothrombin gene variants in non-Caucasians with fetal loss and intrauterine
      growth retardation.
AB  - Thrombotic predisposition may affect pregnancy outcome, but in non-Caucasians the
      contributing genetic factors are poorly characterized. Two recently identified
      prothrombin gene mutations (20209C>T and 20221C>T) have been observed in non
      Caucasian patients with thrombosis. The mutations are located near the commonly
      identified variant 20210G>A and have not been reported in Caucasian patients. The
      authors report a novel connection with pregnancy complications. The
      identification of sequence variants other than 20210G>A in the 3'-untranslated
      region of the prothrombin gene suggests that additional nucleotide substitutions
      may contribute to the development of thrombotic events and adverse pregnancy
      outcomes, especially in less well-characterized populations.

PMID- 14573787
TI  - Antiangiogenic effects of the novel camptothecin ST1481 (gimatecan) in human
      tumor xenografts.
AB  - ST1481 (gimatecan) is a novel lipophilic camptothecin with a promising
      preclinical pharmacological profile. On the basis of its high antitumor efficacy
      when delivered by the oral route, the compound is suitable for prolonged
      administration. This schedule of treatment has been reported as the most
      appropriate to exploit the antiangiogenic effects of cytotoxic drugs. The aim of
      the study was to investigate the antiangiogenic and antitumor effects of oral
      ST1481 in human tumor xenografts. In spite of a marginal drug effect against the
      s.c. growing A549 lung carcinoma following administration with an intermittent
      schedule (q4dx4 times, maximum tolerated dose: 2 mg/kg), tumor growth was
      strongly inhibited by a daily low-dose (0.5 mg/kg) prolonged administration.
      Immunohistochemical analysis showed a reduced number of microvessels in tumors of
      both treated groups versus controls and a significantly higher reduction in the
      daily versus the q4dx4-treated tumors (P < 0.0001, by Student's t test). In our
      experimental model, the relation between microvessel density and tumor size (r =
      0.738, by the Spearman rank test) suggests a role of inhibition of tumor
      vasculature in tumor response. Significant inhibition of tumor angiogenesis (P <
      0.0001 versus control tumors) was observed even with a very low drug dose (0.06
      mg/kg) in the orthotopically implanted (i.d.) MeWo melanoma, under conditions
      causing minimal tumor growth inhibition. Additional evidences of the
      antiangiogenic activity of ST1481 were provided by antimotility effects on
      endothelial cells, in vivo inhibition of vascularization in the Matrigel assay,
      and down-regulation of the expression of the proangiogenic basic fibroblast
      growth factor in A549 tumor cells associated with inhibition of the pathway
      involving Akt. In conclusion, the available results support the possibility that
      the antiangiogenic properties of ST1481 contribute to its antitumor potential and
      that this effect might be enhanced by the continuous low-dose treatment.

PMID- 14573788
TI  - Secretion of extracellular superoxide dismutase from muscle transduced with
      recombinant adenovirus inhibits the growth of B16 melanomas in mice.
AB  - A number of reports have described the effects of oxidative stress on tumor
      growth. Therefore, these experiments were designed to test the hypothesis that
      overexpression of extracellular superoxide dismutase (ecSOD) would inhibit the
      growth of tumors arising from s.c. implantation of syngenic B16-F1 melanoma
      cells. C57BL/6 mice were infected i.m. with adenovirus containing either beta
      galactosidase (Ad.lacZ) as control or the secreted extracellular isoform of SOD
      (Ad.ecSOD) 3 days before s.c. implantation of B16-F1 tumor cells. Serum SOD
      activity was elevated nearly approximately 5-fold over control animals. Two weeks
      after implantation, B16-F1 tumor size was 65% smaller in mice infected with
      Ad.ecSOD in comparison with mice infected with Ad.lacZ. However, the presence of
      SOD did not affect growth rates of B16-F1 cells in vitro. Consistent with smaller
      tumor volume, tumors from Ad.ecSOD-infected mice also expressed less vascular
      endothelial growth factor (VEGF). Moreover, in vitro studies using B16-F1 cells
      confirm that SOD blunts oxidant-dependent VEGF expression. Importantly, CD31
      expression and vessel density were markedly reduced in tumors from Ad.ecSOD
      infected mice compared with controls. These data suggest that tumor oxidative
      stress may facilitate tumor vascularization and thus promote tumor growth.

PMID- 14573789
TI  - Reduced accumulation of specific microRNAs in colorectal neoplasia.
AB  - Short non-coding RNAs are known to regulate cellular processes including
      development, heterochromatin formation, and genomic stability in eukaryotes.
      Given the impact of these processes on cellular identity, a study was undertaken
      to investigate possible changes in microRNA (miRNA) levels during tumorigenesis.
      A total of 28 different miRNA sequences was identified in a colonic
      adenocarcinoma and normal mucosa, including 3 novel sequences and a further 7
      that had previously been cloned only from mice. Human homologues of murine miRNA
      sequences, miR-143 and miR-145, consistently display reduced steady-state levels
      of the mature miRNA at the adenomatous and cancer stages of colorectal neoplasia.

PMID- 14573790
TI  - Phospholipid scramblase 3 controls mitochondrial structure, function, and
      apoptotic response.
AB  - Phospholipid scramblase 3 (PLS3) is a newly recognized member of a family of
      proteins responsible for phospholipid translocation between two lipid
      compartments. To study PLS3 function in mitochondria, we disrupted its conserved
      calcium-binding motif yielding an inactive mutant PLS3(F258V). Cells transfected
      with PLS3(F258V) exhibited reduced proliferative capacity. Mitochondrial analysis
      revealed that PLS3(F258V)-expressing cells have decreased mitochondrial mass
      shown by lower cytochrome c and cardiolipin (CL) content, poor mitochondrial
      respiration, and reduced oxygen consumption and intracellular ATP; whereas wild
      type PLS3-transfected cells exhibit increased mitochondrial mass and enhanced
      respiration. Electron microscopic examination revealed that the mitochondria in
      PLS3(F258V)-expressing cells have densely packed cristae and are fewer in number
      and larger than those in control cells. The abnormal mitochondrial metabolism and
      structure in PLS3(F258V)-expressing cells were associated with decreased
      sensitivity to UV- and tBid-induced apoptosis and diminished translocation of CL
      to the mitochondrial outer membrane. In contrast, wild-type PLS3-transfected
      cells displayed increased sensitivity to apoptosis and enhanced CL translocation.
      These studies identify PLS3 as a critical regulator of mitochondrial structure
      and respiration, and CL transport in apoptosis.

PMID- 14573791
TI  - A retinoid/butyric acid prodrug overcomes retinoic acid resistance in leukemias
      by induction of apoptosis.
AB  - Some success in overcoming retinoic acid (RA)-resistance has been reported for
      acute promyelocytic leukemia in cell lines and the clinic by combining histone
      deacetylase inhibitors, like sodium butyrate (NaB), with RA. This epigenetic
      therapy counteracts the effects of nuclear corepressors, causing a DNA
      conformation that facilitates RA-induced gene transcription and cell
      differentiation. In an effort to improve delivery of each drug, we have
      synthesized retinoyloxymethyl butyrate (RN1), a mutual prodrug of both RA and
      butyric acid. RN1 targets both drugs to the same cells or cellular compartments
      to achieve differentiation at lower concentrations than using RA and NaB alone.
      In an RA-resistant cell line, which is not responsive to RA and NaB given
      together at the same concentration, RN1 inhibited growth substantially. This
      growth inhibition is caused by an increase in apoptosis and a minimal induction
      of differentiation, rather than the more complete granulocytic differentiation as
      seen in the RA-sensitive cell line. The different phenotypes induced by RN1 in RA
      sensitive versus RA-resistant cells are reflected by altered patterns of gene
      expression. In addition to acute promyelocytic leukemia cells, RN1 induces
      apoptosis of other RA-resistant leukemic cell lines with blocked transcriptional
      pathways, but not normal human peripheral blood mononuclear cells. RN1,
      therefore, is a novel retinoid that may be more widely active in hematologic
      malignancies than RA alone.

PMID- 14573792
TI  - Interactive competition between homologous recombination and non-homologous end
      joining.
AB  - DNA-dependent protein kinase (DNA-PK), composed of Ku70, Ku80, and the catalytic
      subunit (DNA-PKcs), is involved in double-strand break (DSB) repair by non
      homologous end joining (NHEJ). DNA-PKcs defects confer ionizing radiation
      sensitivity and increase homologous recombination (HR). Increased HR is
      consistent with passive shunting of DSBs from NHEJ to HR. We therefore predicted
      that inhibiting the DNA-PKcs kinase would increase HR. A novel DNA-PKcs inhibitor
      (1-(2-hydroxy-4-morpholin-4-yl-phenyl)-ethanone; designated IC86621) increased
      ionizing radiation sensitivity but surprisingly decreased spontaneous and DSB
      induced HR. Wortmannin also inhibits DNA-PKcs and reduces DSB-induced HR. IC86621
      did not affect HR product outcome, indicating that it affects HR initiation.
      Thus, HR is increased in the absence of DNA-PKcs, but decreased when DNA-PKcs is
      catalytically inactive, suggesting interactive competition between HR and NHEJ.
      The effects of IC86621 and wortmannin were proportional to the level of DNA-PKcs,
      consistent with inhibited DNA-PKcs acting in a dominant negative manner. We
      propose that inhibition of DNA-PKcs blocks its autophosphorylation, prevents
      dissociation of DNA-PKcs from DNA ends, and thereby blocks both HR and NHEJ. By
      blocking the two major DSB repair pathways, DNA-PKcs inhibitors should
      radiosensitize at all cell-cycle stages and are therefore excellent candidates
      for augmenting cancer radiotherapy.

PMID- 14573793
TI  - Transcription factor AP-2gamma stimulates proliferation and apoptosis and impairs
      differentiation in a transgenic model.
AB  - AP-2 transcription factors play pivotal roles in orchestrating embryonic
      development by influencing the differentiation, proliferation, and survival of
      cells. Furthermore, AP-2 transcription factors have been implicated in
      carcinogenesis, a process where the normal growth and differentiation program of
      cells is disturbed. To experimentally address the potential involvement of AP-2
      in mammary gland tumorigenesis, we generated mice overexpressing AP-2gamma by
      transgenesis using the mouse mammary tumor virus-long terminal repeat as the
      transgene-driving promoter unit. In the mammary gland, transgene expression
      elicited a hyperproliferation that, however, was counterbalanced by the enhanced
      apoptosis of epithelial cells leading to a hypoplasia of the alveolar epithelium
      during late pregnancy. In addition, secretory differentiation was impaired,
      resulting in a lactation failure. In male transgenic mice, the seminal vesicles
      were sites of strong transgene expression. There the effects of AP-2gamma on
      proliferation and apoptosis were even more pronounced, and differentiation was
      impaired, too, as revealed by the absence of androgen receptor immunoreactivity.
      In both tissues, the mammary gland and the seminal vesicles, enhanced steady
      state transcript levels of the AP-2 target gene IGFBP-5 were detected, revealing
      a potential mechanism of AP-2-induced apoptosis. Our results suggest a role of AP
      2 transcription factors in the maintenance of a proliferative and
      undifferentiated state of cells, characteristics not only important during
      embryonic development but also in tumorigenesis.

PMID- 14573794
TI  - Genetic content and evolution of adenoviruses.
AB  - This review provides an update of the genetic content, phylogeny and evolution of
      the family Adenoviridae. An appraisal of the condition of adenovirus genomics
      highlights the need to ensure that public sequence information is interpreted
      accurately. To this end, all complete genome sequences available have been
      reannotated. Adenoviruses fall into four recognized genera, plus possibly a
      fifth, which have apparently evolved with their vertebrate hosts, but have also
      engaged in a number of interspecies transmission events. Genes inherited by all
      modern adenoviruses from their common ancestor are located centrally in the
      genome and are involved in replication and packaging of viral DNA and formation
      and structure of the virion. Additional niche-specific genes have accumulated in
      each lineage, mostly near the genome termini. Capture and duplication of genes in
      the setting of a 'leader-exon structure', which results from widespread use of
      splicing, appear to have been central to adenovirus evolution. The antiquity of
      the pre-vertebrate lineages that ultimately gave rise to the Adenoviridae is
      illustrated by morphological similarities between adenoviruses and
      bacteriophages, and by use of a protein-primed DNA replication strategy by
      adenoviruses, certain bacteria and bacteriophages, and linear plasmids of fungi
      and plants.

PMID- 14573795
TI  - Identification and characterization of a cluster of transcription start sites
      located in the E6 ORF of human papillomavirus type 16.
AB  - Human papillomavirus type 16 (HPV-16) is the prototype strain among the malignant
      types of HPV in the western world. The main promoter, P97, located in front of
      the E6 ORF, has been shown to control expression of the oncogenes E6 and E7.
      These oncogenes are expressed continuously in HPV-16-transformed cells. In
      contrast to malignant HPV types, non-malignant HPV types have separate promoters
      driving the expression of E6 and E7. Experiments have shown that the translation
      of E7 is more efficient from monocistronic than bicistronic transcripts encoding
      both E6 and E7. Here, identification of a cluster of transcription start sites
      located in the E6 ORF of HPV-16 is presented. Transcripts from this region
      contain the E7 ORF as the first reading frame. The cluster consists of multiple
      transcription start sites located around nt 441. Additional transcription start
      sites were identified in a cluster around nt 480. A transcription start site has
      been identified previously at nt 480 but has never been characterized further.
      The region responsible for transcription activity was mapped to nt 272-448.
      Mutational analysis showed that initiation of transcription is independent of a
      TATA-box element, which is consistent with the finding of multiple transcription
      start sites. Furthermore, it is shown that proteins from HeLa and SiHa nuclear
      cell extracts bind to the two regions at nt 291-314 and 388-411, and that these
      two regions influence transcription activity in a cell type-dependent manner.

PMID- 14573796
TI  - Presence of bovine papillomavirus type 2 DNA and expression of the viral
      oncoprotein E5 in naturally occurring urinary bladder tumours in cows.
AB  - Samples of neoplastic and normal urothelium were obtained from cows originating
      from areas of southern Italy, a region in which chronic enzootic haematuria is
      endemic and bracken fern infestation is widespread. Specimens were analysed for
      bovine papillomavirus type 2 (BPV-2) DNA, BPV-2 E5 expression and telomerase
      activity. A total of 46 of 60 tumours and 17 of 34 normal bladder mucosa samples
      harboured BPV-2 DNA. Analysis of a subset of samples showed E5 protein expression
      and telomerase activity in tumour tissue only. No normal samples positive for BPV
      DNA showed E5 protein expression or telomerase activity, suggesting the presence
      of DNA in a latent state. Taken together, these data on naturally occurring
      bovine bladder tumours corroborate the hypothesis of their virus origin.

PMID- 14573797
TI  - Role of sialic acid-containing molecules and the alpha4beta1 integrin receptor in
      the early steps of polyomavirus infection.
AB  - Murine polyomavirus (MPyV) infection occurs through recognition of sialic acid
      (SA) residues present on the host cell membrane, but the nature of the molecules
      involved and the exact role of this interaction in virus cell entry still need to
      be clarified. In this work, mutations at residues R(77) or H(298) of the MPyV VP1
      protein were shown to lead to a complete loss of virus infectivity, which,
      however, could be restored by lipofection of virus particles into the cytoplasm
      of the host cells. Using virus-like particles (VLPs), it was demonstrated that
      the non-infectivity of these mutants was due to impaired cell entry caused by
      total abrogation of SA-dependent cell binding. This indicates that SA residues
      are essential primary cell receptors for MPyV. As the alpha4beta1 integrin has
      been identified recently as a cell receptor for MPyV, the relationship, if any,
      was investigated between SA-containing and alpha4beta1 integrin receptors. The
      ability of mutants R(77)Q and H(298)Q and wt VLPs to bind to cells overexpressing
      the alpha4beta1 integrin was studied in SA-positive (BALB/c 3T3 cells and Pro-5
      cells) and SA-deficient (Pro5-derived Lec-2 cells) backgrounds. Overexpression of
      alpha4beta1 integrin did not restore binding of mutant VLPs in any of these cell
      lines or, indeed, that of wt VLPs in a SA-deficient background. Moreover,
      evidence is provided that overexpression of the sialylated alpha4beta1 integrin
      enhances wt VLP cell binding, suggesting that, in addition to its function at a
      post-attachment level, alpha4beta1 integrin acts also as one of the SA-containing
      receptors for initial cell binding.

PMID- 14573798
TI  - Identification of a sequence from the genome of porcine circovirus type 2 with an
      inhibitory effect on IFN-alpha production by porcine PBMCs.
AB  - Porcine circovirus type 2 (PCV-2) has been identified as the causal agent of
      postweaning multisystemic wasting syndrome and has been associated with several
      other disease syndromes in pigs. To date, however, little is known regarding the
      mechanism(s) underlying the pathogenesis of PCV-2-induced diseases and the
      interaction of the virus with the host immune system. In the present study,
      oligodeoxynucleotides (ODNs), with central CpG motifs selected from the genome of
      PCV-2, were demonstrated to modulate the immune response of porcine PBMCs. Four
      of the five ODNs tested were demonstrated to act in a stimulatory manner via
      induction of IFN-alpha production, whereas only one of the five ODNs showed
      inhibitory activity. Also, this inhibitory ODN was demonstrated to completely
      inhibit IFN-alpha production induced by the other stimulatory ODNs and showed a
      variable degree of inhibitory action on other known inducers of IFN-alpha.
      Although no single common characteristic among resistant or susceptible inducers
      could be identified, the presence of immune modulatory sequences in the genome of
      PCV-2 may represent an underlying mechanism of the pathogenesis of PCV-2
      associated diseases.

PMID- 14573799
TI  - Identification of cis-acting sequences required for selective packaging of bovine
      adenovirus type 3 DNA.
AB  - The assembly of adenovirus particles is a multistep process, in which viral
      genomic DNA is selected and subsequently inserted into preformed empty capsids.
      The selective encapsidation of the adenovirus genome is directed by cis-acting
      packaging motifs, termed A repeats due to their AT-rich character in DNA
      sequence. A repeats are usually located at the left end of the viral genome. In
      this report, the construction and analysis of bovine adenovirus type 3 (BAdV-3)
      mutants containing deletion mutations introduced into the AT-rich regions are
      described. The main cis-acting packaging domains of BAdV-3 were localized between
      nt 224 and 540 relative to the left end of the viral genome. They displayed a
      functional redundancy and followed a hierarchy of importance. In addition, the
      results demonstrated that not all of the AT-rich units functioned as cis-acting
      packaging motifs.

PMID- 14573800
TI  - Transcription factor USF, expressed during the entire phase of varicella-zoster
      virus infection, interacts physically with the major viral transactivator IE62
      and plays a significant role in virus replication.
AB  - The expression of the genes of varicella-zoster virus (VZV) is regulated by self
      encoded viral as well as cellular transcription factors. A potential candidate
      with an ability to influence the transcription of VZV genes is USF (upstream
      stimulatory factor), which recognizes the consensus E-box motif. Quantitative RT
      PCR and immunoblot assays indicate stable expression of both USF1 and USF2
      throughout infection. It was also found that USF binds to a variety of E-boxes
      (consensus and closely related motifs) within the promoters of ORF 8/9 (two
      elements), ORF 22 and ORF 67. Co-immunoprecipitation experiments and His-tag
      protein affinity pull-down assays indicate that a direct physical interaction
      occurs between USF and the major virus transactivator IE62. To study the general
      effects of USF in the replication of VZV, a cell line expressing a dominant
      negative form of USF (A-USF), which inhibits binding of USF to its recognition
      sites, was created. A significant decrease in virus replication was detected when
      this cell line was infected with cell-free virus, indicating that USF is an
      important cellular factor that regulates the transcription of VZV genes.

PMID- 14573801
TI  - Pseudorabies virus (PRV)-specific antibodies suppress intracellular viral protein
      levels in PRV-infected monocytes.
AB  - Blood monocytes infected with pseudorabies virus (PRV), a swine alphaherpesvirus,
      are not eliminated efficiently by antibody-dependent immunity and may
      occasionally transport PRV to the pregnant uterus of vaccinated animals. This
      study examines in vitro the long-term fate of PRV-infected monocytes cultivated
      in the presence of porcine PRV-specific antibodies. All monocytes were infected
      and expressed viral late proteins, and 30 % of PRV-infected monocytes cultivated
      with PRV-specific antibodies survived up to 194 h post-infection (p.i.), the end
      of the experiment (compared to 0 % for cells cultivated with PRV-negative
      antibodies). Of these surviving cells, +/-75 % no longer expressed
      microscopically detectable viral late proteins from 144 h p.i. onwards.
      Remarkably, monocytes infected with a PRV gB-null virus did not survive in the
      presence of PRV-specific antibodies. These data suggest that PRV-specific
      antibodies suppress viral protein levels in infected monocytes, perhaps helping
      the virus to persist and reach internal organs in vaccinated animals.

PMID- 14573802
TI  - The bovine herpesvirus-1 LR ORF2 is critical for this gene's ability to restore
      the high wild-type reactivation phenotype to a herpes simplex virus-1 LAT null
      mutant.
AB  - During neuronal latency of herpes simplex virus (HSV)-1, the latency-associated
      transcript (LAT) is the only viral gene readily detectable. LAT is required for
      the high-level reactivation phenotype in animal models. LAT's anti-apoptotic
      activity was recently demonstrated by our group and it was proposed that LAT's
      anti-apoptotic function is involved in enhancing the reactivation phenotype.
      Recently, using chimeric virus CJLAT, it was shown that the reactivation
      phenotype of LAT(-) mutant dLAT2903 can be restored to wild-type levels by
      inserting the bovine herpes virus (BHV)-1 latency-related (LR) gene into the LAT
      locus of this HSV-1 LAT deletion mutant. Although transcription of the LR gene,
      like LAT, inhibits apoptosis, LR appears to be multifunctional. To investigate
      whether the LR gene's anti-apoptotic function was responsible for restoring the
      high-reactivation phenotype, a mutated BHV-1 LR gene was inserted into the LAT
      locus of HSV-1 generating the chimeric virus CJLATmut. This mutation consists of
      three stop codons inserted just after the ATG of the first LR open reading frame
      (ORF2). In plasmids and in a BHV-1 mutant, this mutation eliminated the LR gene's
      anti-apoptotic activity, strongly suggesting that ORF2 encodes a protein
      responsible for LR's anti-apoptotic activity. Reactivation of the CJLATmut virus,
      in both rabbits and mice, was significantly lower than in wild-type McKrae virus
      (P=0.0001 and P=0.0003, respectively) and CJLAT virus, containing wild-type LR in
      place of LAT (P<0.0001) and was similar to LAT(-) dLAT2903 (P=0.8 and P=0.7,
      respectively). Thus, disruption of BHV-1 LR ORF2 eliminated the high-reactivation
      phenotype.

PMID- 14573803
TI  - Cholesterol-dependent infection of Burkitt's lymphoma cell lines by Epstein-Barr
      virus.
AB  - Epstein-Barr virus (EBV) infection is a multi-step process, first requiring virus
      binding to the host cell, followed by fusion of the viral envelope with the host
      cell plasma membrane. Efficient EBV entry into B cells requires, at the minimum,
      the interaction of the EBV-encoded glycoproteins gp350 with cellular CD21 and
      gp42 with MHC class II proteins. In this study, use of the cholesterol-binding
      drugs methyl-beta-cyclodextrin and nystatin efficiently inhibited EBV infection
      of target Burkitt's lymphoma B-cell lines, indicating an important role for
      cholesterol and suggesting the involvement of lipid rafts in EBV infection.

PMID- 14573804
TI  - Transcript mapping of the 'early' genes of Orf virus.
AB  - The full complement of genes encoded by Orf virus (ORFV) is not yet known. A cDNA
      library was constructed using mRNA isolated 5 h post-infection from cells
      infected with ORFV in vitro and grown in the presence of cytosine arabinoside.
      Using 12 non-overlapping probes representing the entire genome of the Orf-11
      strain of the virus, cDNA clones representing individual genes expressed early in
      infection were isolated. Thirty-eight early genes were identified, either via
      isolation of their cDNA from the library or via Northern blotting. Twenty-nine of
      the isolated cDNAs represented orthologues of other poxvirus genes or had been
      identified previously as genes of ORFV, whilst seven appeared unrelated to any
      known poxvirus gene or indeed to any known gene in the DNA databases. The
      sequences described in this paper constitute approximately 30 kb of the ORFV
      genome and contain the complete or partial sequence of 47 genes.

PMID- 14573806
TI  - Baculovirus P35 interacts with a subunit of human RNA polymerase II and can
      enhance promoter activity in human cells.
AB  - The early protein P35 from the baculovirus Autographa californica
      nucleopolyhedrovirus is a direct inhibitor of caspases and can block apoptosis in
      a wide variety of systems. In addition, it has been linked to the regulation of
      viral gene expression, shut-down of protein synthesis in infected insect cells
      and malignant transformation of mouse fibroblasts. By yeast-two-hybrid screening
      we identified the RPB11a subunit of human RNA polymerase II as an interaction
      partner of P35. Specificity of the interaction was confirmed by affinity
      blotting. By immunocytology, P35 was in part found in the nucleus of transfected
      cells. Homology searches further revealed that P35 has structural similarity with
      RPB3, the subunit of RNA polymerase II that has been demonstrated to interact
      directly with RPB11a. When transfected into human colon carcinoma cells, P35 was
      able to enhance the activity of E-cadherin and beta-actin promoters by about a
      factor of two as measured by luciferase reporter assay. P35 and hRPB11a together
      enhanced the E-cadherin activity about three- to fourfold. These data suggest an
      additional role for P35 in the regulation of cellular transcription.

PMID- 14573805
TI  - Evidence for the evolution of ascoviruses from iridoviruses.
AB  - Ascoviruses (family Ascoviridae) are large, enveloped, double-stranded (ds)DNA
      viruses that attack lepidopteran larvae and pupae, and are unusual in that they
      are transmitted by parasitic wasps during oviposition. Previous comparisons of
      DNA polymerase sequences from vertebrate and invertebrate viruses suggested that
      ascoviruses are closely related to iridoviruses. This relationship was unexpected
      because these viruses differ markedly in virion symmetry, genome configuration
      and cellular pathology. Here we present evidence based on sequence comparisons
      and phylogenetic analyses of a greater range of ascovirus proteins and their
      homologues in other large dsDNA viruses that ascoviruses evolved from
      iridoviruses. Consensus trees for the major capsid protein, DNA polymerase,
      thymidine kinase and ATPase III from representative ascoviruses, algal viruses
      (family Phycodnaviridae), vertebrate and invertebrate iridoviruses (family
      Iridoviridae) and African swine fever virus (ASFV; family Asfarviridae) showed
      that ascovirus proteins clustered most closely with those of the lepidopteran
      iridovirus Chilo iridescent virus (CIV) (Invertebrate iridescent virus 6).
      Moreover, analysis of the presence or absence of homologues of an additional 50
      proteins encoded in the genome of Spodoptera frugiperda ascovirus (SfAV-1a)
      showed that about 40 % occurred in CIV, with lower percentages encoded by the
      genomes of, respectively, vertebrate iridoviruses, phycodnaviruses and ASFV. The
      occurrence of three of these genes in SfAV-1a but not CIV was indicative of the
      evolutionary differentiation of ascoviruses from invertebrate iridoviruses.

PMID- 14573807
TI  - Open reading frame 94 of Helicoverpa armigera single nucleocapsid
      nucleopolyhedrovirus encodes a novel conserved occlusion-derived virion protein,
      ODV-EC43.
AB  - Open reading frame 94 (Ha94) of Helicoverpa armigera single nucleocapsid
      nucleopolyhedrovirus (HaSNPV) is 1086 bp long and a homologue of Autographa
      californica multiple NPV ORF109. The gene is conserved among all baculoviruses
      whose genomes have been completely sequenced so far and is thus considered a
      baculovirus core gene. Ha94 transcripts were detected from 24 to 96 h post
      infection (p.i.) of HzAM1 cells with HaSNPV. Polyclonal antiserum raised to a GST
      HA94 fusion protein recognized a 43 kDa protein, HA94, in infected cell lysates
      from 36 to 96 h p.i., suggesting that Ha94 is a late gene. Western blot analysis
      of proteins present in budded virus and occlusion-derived virus (ODV) showed that
      Ha94 encodes a structural component of ODV. When ODVs were fractionated further
      into nucleocapsid and envelope components, Western blot analysis indicated that
      the encoded protein was associated with both the nucleocapsid and the envelope.
      In summary, data available indicated that Ha94 encodes a novel ODV-specific
      protein of HaSNPV, designated ODV-EC43.

PMID- 14573808
TI  - Autographa californica nucleopolyhedrovirus infection of Spodoptera frugiperda
      cells: a global analysis of host gene regulation during infection, using a
      differential display approach.
AB  - Autographa californica nucleopolyhedrovirus (AcMNPV), the type member of the
      virus family Baculoviridae, infects pest insects and has been the subject of many
      studies for its development as a biopesticide. It is also the virus upon which
      most of the commercial baculovirus protein expression systems are based. AcMNPV
      infection of cultured host Spodoptera frugiperda (Sf9) cells can induce a number
      of alterations of host cell properties including altering the cellular
      cytoskeleton, an arrest of the cell cycle in G(2)/M, and the global shutoff of
      host protein translation. Additionally, several cellular transcripts have been
      shown to be down-regulated following AcMNPV infection. In this study, we take a
      differential display approach to address whether a global down-regulation of Sf9
      host transcripts occurs at late times of infection. Additionally, we also use
      this approach to search for host mRNAs which are up-regulated at early times of
      infection, and may be important for facilitating baculovirus infection. From
      these experiments we can confirm a global down-regulation of Sf9 mRNA levels at
      late times of infection. We also found that up-regulation of individual host gene
      RNA levels at early times of infection did not occur frequently. One host
      transcript which was found to be transiently up-regulated as a result of AcMNPV
      infection was an Sf9 Hsc70 gene. Hsc70 proteins have been shown to play a vital
      role in the life-cycle of other large DNA viruses, which suggests that this
      protein is also important for baculovirus infection.

PMID- 14573809
TI  - Cellular receptor interactions of C-cluster human group A coxsackieviruses.
AB  - The cellular receptor complex of coxsackievirus A21 (CVA21), a C-cluster human
      enterovirus, is formed by the subtle interaction of individual cellular
      receptors, decay accelerating factor (DAF) and intercellular adhesion molecule-1
      (ICAM-1). In this receptor complex, DAF functions in the membrane sequestration
      of the virus, while the role of ICAM-1 is as the functional cellular
      internalization receptor. However, despite the elucidation of the CVA21-cell
      receptor interactions, there have been few definite investigations into cellular
      receptor usage of other coxsackie A viruses (CVAs) belonging to the C-cluster. In
      the present study, radiolabelled virus-binding assays demonstrated that CVA13, 
      15, -18 and -20, a subset of the human enterovirus C-cluster, bind directly to
      surface-expressed ICAM-1, but not to surface-expressed DAF. Furthermore, lytic
      infection of ICAM-1-expressing rhabdomyosarcoma (RD) cells by this C-cluster
      subset of viruses was inhibited by specific ICAM-1 monoclonal antibody blockade,
      except for that of CVA20. Despite possessing ICAM-1-binding capabilities, CVA20
      employed an as yet unidentified internalization receptor for cell entry and
      subsequent productive lytic infection of ICAM-1-negative RD cells. In a further
      example of C-cluster cellular receptor heterogeneity, CVA13 exhibited significant
      binding to the surface of CHO cells expressing neither DAF nor ICAM-1. Despite a
      common receptor usage of ICAM-1 by this subset of C-cluster CVAs, the amino acid
      residues postulated to represent the ICAM-1-receptor footprint were not
      conserved.

PMID- 14573810
TI  - Lack of islet neogenesis plays a key role in beta-cell depletion in mice infected
      with a diabetogenic variant of coxsackievirus B4.
AB  - Group B coxsackieviruses (CVBs) have a well-established association with type 1
      diabetes but the mechanism of depletion of beta-cell mass following infection has
      not yet been defined. In this report we show that the major difference in
      pathogenesis between the E2 diabetogenic strain of CVB4 and the prototypic JVB
      strain in SJL mice is not in tropism for islet cells but in the degree of damage
      inflicted on the exocrine pancreas and the resulting capacity for regeneration of
      both acinar and islet tissue by the host. Both strains replicated to a high titre
      in acinar tissue up to day 3 post-infection (p.i.), while the islets of
      Langerhans were largely spared. However, the pancreas in the JVB-infected animals
      then regenerated and many small islets were seen throughout the tissue by day 10
      p.i. In contrast, the acinar tissue in E2-infected mice became increasingly
      necrotic until all that remained by day 21 p.i. were large islets containing
      varying numbers of dead cells, caught up in strands of connective tissue.
      Surviving beta cells were found to synthesize little insulin, although islet
      amyloid polypeptide was detected and glucagon synthesis in alpha cells appeared
      normal or enhanced. Our results suggest that the key to CVB-E2-induced damage
      lies in the exocrine tissue and prevention of islet neogenesis rather than from
      direct effects on existing islets.

PMID- 14573811
TI  - Isolation and characterization of a new species of kobuvirus associated with
      cattle.
AB  - A cytopathic agent was isolated using Vero cells from the culture medium of HeLa
      cells that had been used for more than 30 years in our laboratory. This agent,
      termed U-1 strain, was serially passed in Vero cells with distinct CPE. Particles
      of U-1 strain negatively stained with phosphotungstic acid exhibited a distinct
      surface that resembled Aichi virus. The RNA genome of U-1 strain comprises 8374
      nt, with a genome organization analogous to that of picornaviruses. Possible
      cleavage sites of the large ORF, which encoded a leader protein prior to the
      capsid protein region, were assigned following amino acid alignment with Aichi
      virus. The virus sequence had 33 and 75 % amino acid identity with the Aichi
      virus VP1 and 3D regions, respectively, but no more than 23 and 36 % with those
      of the prototype strains of other PICORNAVIRIDAE: The dendrogram based on the P1,
      P2 and P3 proteins indicated that U-1 strain is genetically included in the genus
      Kobuvirus but is distinct from Aichi virus. Of 72 cattle sera, 43 (59.7 %) were
      positive for neutralizing antibody against U-1 strain at a titre of 1 : 8 or
      more. However, sera from 190 humans, 242 monkeys, 139 pigs, 5 horses, 22 dogs and
      9 cats did not neutralize U-1 strain at a 1 : 4 dilution. RNA corresponding to U
      1 strain was detected in 12 (16.7 %) of 72 faecal samples from cattle by RT-PCR.
      These results indicated that U-1 strain, suspected to be a contaminant from calf
      sera, is a new species of the genus Kobuvirus, now termed bovine kobuvirus.

PMID- 14573812
TI  - Long-term survival of New Zealand rabbit haemorrhagic disease virus RNA in wild
      rabbits, revealed by RT-PCR and phylogenetic analysis.
AB  - Because Rabbit haemorrhagic disease virus (RHDV) is highly pathogenic for
      rabbits, farmers illegally introduced it as a bio-control agent onto New Zealand
      farms in 1997. The virus was dispersed rapidly, initially causing high fatality
      rates in rabbits. Nevertheless, many survived and these surviving rabbits have
      been investigated for evidence of infection by RHDV. Livers from healthy rabbits
      contained RHDV-specific RNA, as shown by nested RT-PCR sequencing. The sequences
      of the viral capsids were related closely to the released Czech strain of RHDV,
      although the sequence from one rabbit was related most closely to a Spanish
      strain of RHDV. Phylogenetic analysis of the capsid sequences of 38 samples
      implied that there have been at least two introductions of the Czech virus into
      New Zealand, probably corresponding firstly to the original illegal introduction
      by farmers and secondly to the introduction of the same virus under governmental
      control. Genomic length sequence of two samples was obtained, suggesting that
      they may have retained the potential to be infectious, although this has not yet
      been demonstrated. The detection of genomic-length RNA in the liver of healthy
      rabbits suggests that even though a highly virulent virus was introduced into New
      Zealand, it rapidly established persistent or latent infections in a proportion
      of rabbits. This might account for their ability to survive in the face of
      virulent released virus. Moreover, the co-circulation of other strains of RHDV in
      the same rabbit population, such as the Spanish strain, might also impact on
      their susceptibility to the bio-control agent.

PMID- 14573813
TI  - Molecular characterization of a novel astrovirus associated with disease in mink.
AB  - Pre-weaning diarrhoea is a well-known problem in mink farming in Europe, causing
      morbidity that varies between farms, regions and season. Different causalities
      for the disease have been proposed, but only most recently has a novel astrovirus
      been identified as an important risk factor. In this report, the molecular
      characterization, origin and evolution of this novel astrovirus of mink are
      discussed. The polyadenylated, positive-stranded RNA genome was sequenced and
      found to contain 6610 nt, organized into three ORFs and two short UTRs. A
      ribosomal frameshift sequence links the 5' two ORFs, containing sequence motifs
      for a serine protease (ORF1a) and an RNA-dependent RNA polymerase (ORF1b). The
      structural proteins are encoded by ORF2 and, presumably, are expressed as a
      polyprotein precursor to be cleaved into the mature capsid proteins. These
      results indicate that mink astrovirus (MiAstV) has all of the features typical of
      members of the Astroviridae. Phylogenetic analyses revealed that MiAstV is
      distantly related to established astroviruses, showing less than 67 % similarity
      at the nucleotide level with its closest relative, ovine astrovirus, and even
      lower identities at the predicted amino acid level. Nevertheless, sequence
      analysis of MiAstV isolates from geographically distinct Swedish and Danish farms
      showed much less diversity. This suggests either the spread in the mink
      population of a virus that has evolved a long time ago or the recent introduction
      of an ancient virus into a new host species.

PMID- 14573814
TI  - Dengue virus type 2 infects human endothelial cells through binding of the viral
      envelope glycoprotein to cell surface polypeptides.
AB  - The endothelial cell line ECV304, derived from human umbilical cord and
      identified to be susceptible to dengue virus type 2 (DEN-2) infection, was used
      to study the molecular mechanism of DEN-2 binding to endothelial cells. DEN-2 was
      found by virus overlay protein-binding assays (VOPBAs) to bind to three ECV304
      cell membrane proteins with molecular masses of 29, 34 and 43 kDa. Only a single
      protein of 29 kDa was observed when VOPBAs were carried out using preparations of
      trypsin-treated ECV304 cells. Pre-incubation of live ECV304 cells in culture or
      cell membrane proteins in modified VOPBAs with the recombinant DEN-2 envelope
      glycoprotein (rEgp) inhibited DEN-2 infection and blocked virus binding to the
      three proteins identified. These results indicate that DEN-2 rEgp could bind to
      three proteins on the surface of ECV304 cells. This virus-cell interaction may be
      associated with the receptor complex specific for DEN-2 infection of endothelial
      cells.

PMID- 14573815
TI  - A reverse genetics system for Borna disease virus.
AB  - Borna disease virus (BDV) is an enveloped virus. Its non-segmented, negative
      stranded RNA genome has the coding capability for six main polypeptides and has
      an organization characteristic of members of the order Mononegavirales. However,
      based on its unique genetics and biological features, BDV is considered to be the
      prototypic member of a new virus family, Bornaviridae. Here, the establishment of
      a reverse genetics system for BDV is described. Intracellular synthesis of a BDV
      RNA analogue or minigenome (MG) from a plasmid was driven by RNA polymerase I. Co
      transfection with plasmids expressing the BDV polymerase (L), nucleoprotein (N)
      and phosphoprotein (P) under the control of RNA polymerase II allowed for BDV MG
      replication and expression. This process depended on a delicate N:P ratio,
      whereas the L:P ratio was less critical. Two isoforms of N, Np40 and Np38, are
      present in BDV-infected cells but only Np40 was strictly required for virus
      polymerase activity. BDV p10 polypeptide encoded by the P gene exhibited a strong
      inhibitory effect on BDV MG expression.

PMID- 14573816
TI  - Conserved cysteine and histidine residues in the putative zinc finger motif of
      the influenza A virus M1 protein are not critical for influenza virus
      replication.
AB  - The influenza virus matrix protein (M1) possesses a cysteine and histidine (CCHH)
      motif in the helix 9 (H9) and adjacent region ((148)CATCEQIADSQHRSH(162)). The
      CCHH motif has been proposed as a putative zinc finger motif and zinc-binding
      activity has been implicated in virus uncoating as well as transcription
      inhibition and mRNA regulation. The function of the CCHH motif in the influenza
      virus life cycle was investigated by site-directed mutagenesis (alanine
      replacement) and by rescuing mutant viruses by reverse genetics. Mutant viruses
      containing an alanine replacement of the cysteine and histidine residues, either
      individually or in combination, were seen to exhibit wt phenotype in multiple
      virus growth cycles and plaque morphology. In addition, synthetic peptides
      containing the putative zinc finger motif did not inhibit virus replication in
      MDCK cells. However, mutation of Ala(155) in H9 was lethal for rescuing
      infectious virus. These data show that the CCHH motif does not provide a critical
      function in the influenza virus life cycle in cell culture and that the zinc
      binding function may not be involved in virus biology. However, the lethal
      phenotype of the Ala(155) mutation shows that the H9 region of M1 provides some
      other critical function(s) in virus replication.

PMID- 14573817
TI  - Major changes in the G protein of human respiratory syncytial virus isolates
      introduced by a duplication of 60 nucleotides.
AB  - The entire nucleotide sequence of the G gene of three human respiratory syncytial
      virus (HRSV) isolates (antigenic group B) has been determined. These three
      viruses (named BA viruses) were isolated in Buenos Aires in 1999 from specimens
      collected in different hospitals and at different dates. BA viruses have an exact
      duplication of 60 nucleotides in the G gene, starting after residue 791. This
      duplication is flanked by a repeat of four nucleotides (GUGU) and can fold into a
      relatively stable secondary structure. These features suggest a possible
      mechanism for the generation of a duplicated G segment. The predicted polypeptide
      is lengthened by 20 amino acids (residues 260-279) and this is reflected in the
      slower electrophoretic mobility of the G protein precursor of BA viruses compared
      with related viruses. The changes reported here expand the examples of drastic
      genetic alterations that can be introduced into the G protein sequence of HRSV
      while it replicates in its natural host.

PMID- 14573818
TI  - Contribution of the length of the HN protein and the sequence of the F protein
      cleavage site to Newcastle disease virus pathogenicity.
AB  - Newcastle disease virus (NDV) possesses two envelope spike glycoproteins: the
      haemagglutinin-neuraminidase (HN) protein and the fusion (F) protein. The HN
      protein, which is responsible for virus attachment to sialic acid-containing
      receptors, varies in length due to differences in the sizes of the ORFs. An HN
      protein precursor of 616 aa has been found in avirulent but not in virulent NDV
      strains, whereas an HN protein of 571 aa can be detected in highly virulent
      strains only. An HN protein of 577 aa is present in virulent and avirulent
      strains. The F protein, which mediates virus-cell fusion, requires proteolytic
      activation at an internal cleavage site, whose amino acid composition determines
      cleavability by various proteases. Here, the functional significance of the
      length of the HN protein in combination with F protein cleavage sites typical for
      virulent (velogenic and mesogenic) or avirulent (lentogenic) strains was
      investigated. To this end, site-directed mutagenesis was used to construct
      recombinant NDV on the basis of an infectious clone of the lentogenic vaccine
      virus Clone-30. Only recombinant NDV expressing an F protein with a multibasic
      cleavage site typical of virulent strains was able to spread efficiently in cell
      culture, irrespective of the size of the HN protein. Moreover, as determined by
      the intracerebral pathogenicity index (ICPI) in 1-day-old, specific-pathogen-free
      chickens, pathogenicity was influenced by the cleavability of the F protein and
      not by the length of the HN protein. The maximum ICPI value obtained for these
      recombinants was 1.3, as compared to a possible maximum of 2. This demonstrates
      that the modifications introduced did not result in the conversion of the
      lentogenic Clone-30 to a velogenic strain with an ICPI value of >1.5 and suggests
      the involvement of additional virulence determinants that contribute to the
      pathogenicity of NDV.

PMID- 14573819
TI  - Retrovirus vector production and transduction: modulation by the cell cycle.
AB  - In this study, the cell cycle modulation of retrovirus vector production and
      transduction was analysed. Retrovirus vector expression was found to be similar
      in all phases of the cell cycle and, in contrast to some other virus promoters
      shown previously to be upregulated by G(2)/M arrest, Moloney murine leukaemia
      virus LTR-driven expression was upregulated neither by G(2)/M growth arrest nor
      by G(1)/S growth arrest. In contrast, cultures enriched for S phase cells
      produced more infectious virions, apparently by modulation of stages consequent
      to provirus expression. In terms of retrovirus transduction, limitations appear
      to be slow progression through the cell cycle and short half-life of the virus.
      Synchronization of cells prior to mitosis can increase transduction efficiency.
      Cell cycle modulation can be used to modify retrovirus vector production and
      transduction and can allow short transduction periods.

PMID- 14573820
TI  - Complete nucleotide sequence of Pelargonium zonate spot virus and its
      relationship with the family Bromoviridae.
AB  - The complete sequence of the Pelargonium zonate spot virus (PZSV) genome was
      determined. It comprises 8477 nt, distributed in three positive-strand RNA
      species encoding four proteins. RNA-1 is 3383 nt long, with an ORF that encodes a
      polypeptide with a molecular mass of 108 419 Da (denoted protein 1a). This
      protein contains the conserved sequence motifs I-III of type I methyltransferases
      and the seven consensus motifs of the helicases of superfamily 1. RNA-2 is 2435
      nt long and encodes a major polypeptide with a molecular mass of 78 944 Da
      (denoted protein 2a), which shows identity to the RNA-dependent RNA polymerases
      of positive-strand RNA viruses. RNA-3 is 2659 nt long and contains two major
      ORFs. The first ORF is located in the 5' portion of the genome and sequence
      comparison of the putative translation product revealed similarities with the 30K
      superfamily of virus movement proteins. The second ORF is located in the 3' half
      and encodes the viral coat protein, which is expressed via a subgenomic RNA, RNA
      4. The transcription initiation site of RNA-4 maps to the intergenic region of
      RNA-3. The organization of the PZSV genome, including the primary structure of
      terminal non-coding regions, strongly suggests that this virus belongs to the
      family Bromoviridae. The overall biological and genomic characteristics of PZSV
      indicate affinities in diverging directions with one or other of the virus
      species in this family, thus enabling it to be considered as a possible
      representative of a new genus within the family Bromoviridae.

PMID- 14573821
TI  - Evidence that the 37 kDa protein of Soil-borne wheat mosaic virus is a virus
      movement protein.
AB  - Experiments were conducted to determine if the 37 kDa protein (37K) of Soil-borne
      wheat mosaic virus (SBWMV) is a virus movement protein. First, evidence was
      obtained that indicated that 37K has the ability to move from cell to cell,
      similar to other virus movement proteins (MPs). Plasmids containing the GFP gene
      fused to the SBWMV 37K, the coat protein (CP) or the CP readthrough domain (RT)
      ORFs were delivered by biolistic bombardment to wheat and tobacco leaves. In
      wheat leaves, cell-to-cell movement of GFP-37K was observed, while GFP, GFP-CP
      and GFP-RT accumulated primarily in single cells. All fusion proteins accumulated
      in single cells in tobacco leaves. Thus, cell-to-cell movement is a specific
      property of 37K that occurs in SBWMV host plants. Subcellular accumulation of 37K
      was studied using SBWMV-infected and 37K-expressing transgenic wheat. In infected
      and transgenic wheat leaves, 37K accumulated in the cell wall, similar to other
      virus MPs, and in aggregates in the cytoplasm. Phylogenetic studies were
      conducted to compare the furovirus 37K proteins with members of the 30K
      superfamily of virus MPs. Amino acid sequences of the furovirus 37K proteins were
      aligned with the MPs from 43 representative viruses. The furovirus 37K proteins
      were found to reside in a clade that also contained the dianthovirus MPs.
      Combined, these data suggest that SBWMV 37K is probably a virus MP.

PMID- 14573822
TI  - Transmission of murine scrapie to P101L transgenic mice.
AB  - The PrP protein is central to the transmissible spongiform encephalopathies
      (TSEs), and the amino acid sequence of this protein in the host can influence
      both incubation time of disease and targeting of disease pathology. The N
      terminus of murine PrP has been proposed to be important in the replication of
      TSE agents, as mutations or deletions in that region can alter the efficiency of
      agent replication. To address this hypothesis and to investigate the mechanisms
      by which host PrP sequence controls the outcome of disease, we have assessed the
      influence of a single amino acid alteration in the N-terminal region of murine
      PrP (P101L) on the transmission of TSE agents between mice. Mice homozygous for
      the mutation (101LL) were inoculated with TSE strains 139A and 79A derived from
      mice carrying a Prnp(a) allele, and 79V and 301V derived from mice carrying a
      Prnp(b) allele. Incubation times in 101LL mice were extended with all four
      strains of agent when compared with those in the corresponding mouse genotype
      from which the infectivity was derived. However, the degree to which the
      incubation period was increased showed considerable variation between each strain
      of agent. Moreover, the presence of this single amino acid alteration resulted in
      a 70 day reduction in incubation time of the 301V strain in Prnp(a) mice. The
      effect of the 101L mutation on murine scrapie incubation time appears therefore
      to be strain specific.

PMID- 14573823
TI  - Sodium hydroxide renders the prion protein PrPSc sensitive to proteinase K.
AB  - Sodium hydroxide (NaOH) solutions are widely used for the purification of
      contaminated equipment, as they are known to inactivate a variety of pathogens.
      However, information about their effect on agents causing transmissible
      spongiform encephalopathy (TSE) is sparse and contradictory. Scrapie hamster
      brain homogenate, containing the disease-associated form of the prion protein
      (PrP(Sc)), was exposed to NaOH. Kinetics studies showed that treatment of brain
      homogenate with millimolar concentrations of NaOH rapidly abolished the
      proteinase K-resistant form of the prion protein (PrP(res)). NaOH treatment
      converted PrP(Sc) into a protease-sensitive form, either in solution or when
      adsorbed to a metallic surface. If infectivity of TSEs is linked with PrP(res),
      the results imply that inactivation of TSE occurs more efficiently than currently
      assumed.

PMID- 14573825
TI  - Staff training in integrated sexual health services.

PMID- 14573826
TI  - Validity and utility of screening tests for STIs.

PMID- 14573827
TI  - Managing partners of people diagnosed with Chlamydia trachomatis: a comparison of
      two partner testing methods.
AB  - OBJECTIVE: To compare the effectiveness of "home sampling" with that of "office
      sampling" for testing partners to men and women infected with Chlamydia
      trachomatis. METHOD: A randomised controlled effectiveness trial took place in
      the general community in Denmark. 1300 index women and 526 index men (>/=18
      years) with a positive test result for C trachomatis were identified. Of these,
      414 index women and 148 index men gave implied consent. Index patients were
      randomly assigned to provide their partner(s) through the past 12 months with
      either (1) a kit by which partner(s) could be tested by home sampling, or (2) a
      kit by which partner(s) could only be tested by seeing a healthcare professional
      (office sampling). The mainoutcome measure was the proportion of index patients
      who had at least one partner tested for C trachomatis. RESULTS: The proportion of
      index women with at least one partner tested was higher in the home sampling
      group (0.26) than in the office group (0.12) (difference 0.14; 95% CI 0.10 to
      0.19; p<0.0001) and so it was for index men (0.15 v 0.03; difference 0.12; 95% CI
      0.07 to 0.16; p<0.0001). Also the proportion of index women for whom at least one
      partner was identified as infected was higher in the home sampling group compared
      with the office group (0.11 v 0.07, p=0.01). The corresponding figures for index
      men were 0.06 v 0.01, p=0.02. CONCLUSION: The effectiveness of partner testing is
      higher when partners of C trachomatis infected patients are offered home sampling
      than when they are offered office sampling.

PMID- 14573829
TI  - Sensitivity requirements for the point of care diagnosis of Chlamydia trachomatis
      and Neisseria gonorrhoeae in women.
AB  - BACKGROUND/OBJECTIVES: Most current tests for Neisseria gonorrhoeae and Chlmydia
      trachomatis require the support of a laboratory, and results are not usually
      available before the patient has left the clinic. This delay can lead to patients
      not returning for treatment and may allow further STI transmission to occur.
      Current rapid point of care (POC) STI tests and the syndromic approach are less
      sensitive than gold standard tests, but allow treatment at the initial visit.
      This study estimates the required sensitivity of POC tests that ensures as many
      STIs are averted as with current gold standard tests. METHODS: A mathematical
      model is developed to compare the STIs averted using different STI diagnostic
      methods. Data from Benin, South Africa, Tanzania, and England are used to explore
      how the required sensitivity differs between settings. RESULTS: The required
      sensitivity of a POC test is low if there is significant STI transmission during
      the delay in treatment for the gold standard test and/or few women return for
      treatment. For example, the required sensitivity of a POC test for C trachomatis
      is 50% (gold standard test sensitivity is 90%) if either 55% return for treatment
      and there is no STI transmission, or 80% return for treatment and 50% of infected
      women infect their partner during the delay in treatment. Furthermore, in these
      settings a POC test of moderate sensitivity can lead to significantly more STI
      averted than the gold standard test. CONCLUSIONS: These results support the use
      of moderate sensitivity POC tests in scenarios where many women will not return
      for treatment, and in populations where the delay in treatment would result in
      significant STI transmission.

PMID- 14573830
TI  - Shared care in the management of genital Chlamydia trachomatis infection in
      primary care.
AB  - OBJECTIVES: To investigate the impact of a health adviser in genitourinary
      medicine as a training and support resource on the management of Chlamydia
      trachomatis in a large inner city health centre. METHODS: A large, inner city
      health centre was selected at random for the intervention, with another selected
      as control. The health adviser offered support and training in the management of
      C trachomatis to clinical staff in the intervention health centre for 6 months.
      Data on testing activity were collected over the period of the intervention and
      during the equivalent period in the previous year. Data on partner notification
      activities were collected from case notes. RESULTS: The research intervention was
      effective in increasing C trachomatis testing activity. However, the majority of
      tests were offered to women over 20 years of age and no increase in the
      proportion of positive results was observed. CONCLUSIONS: The intervention was
      effective in increasing C trachomatis testing activity, but did not improve the
      overall detection rate. Health centre staff accommodated opportunistic testing
      for C trachomatis into existing healthcare practices, as opposed to introducing
      new screening systems designed to reach the target population.

PMID- 14573831
TI  - Sex differences in the experience of testing positive for genital chlamydia
      infection: a qualitative study with implications for public health and for a
      national screening programme.
AB  - OBJECTIVES: To explore men's and women's accounts of chlamydia testing, with a
      view to understanding sex differences in attitudes and in behaviours of public
      health importance. METHODS: Semistructured interviews with 24 heterosexual
      patients (12 men; 12 women) diagnosed with genital chlamydia infection, at a
      large sexual health clinic in central London were transcribed and analysed using
      qualitative thematic analysis. RESULTS: Participants' expressions revealed
      important sex differences. Women felt anxious about their future reproductive
      health, feared stigmatisation, and blamed themselves for contracting chlamydia;
      whereas men generally reported less concern, were unwilling to disclose their
      condition to sexual partners, and some men projected attributions of blame onto
      their partners. Delays in seeking care appeared to be related to perceptions of
      chlamydia as a relatively minor infection, particularly in men. CONCLUSIONS:
      Health promotion needs to reflect sex and age differences, emphasising the
      negative consequences of delayed clinic attendance and exposure to repeat
      infections. For health professionals to respond appropriately and effectively to
      increasing numbers of chlamydia infections, there is a need to understand men's
      avoidant attitudes and behaviours in relation to sexual and reproductive health.

PMID- 14573832
TI  - Is antenatal syphilis screening still cost effective in sub-Saharan Africa.
AB  - OBJECTIVES: To estimate the cost effectiveness of on-site antenatal syphilis
      screening and treatment in Mwanza, Tanzania. To compare this intervention with
      other antenatal and child health interventions, specifically the prevention of
      mother to child transmission of HIV (PMTCT). METHODS: The economic costs of
      adding the intervention to routine antenatal care were assessed. Cost
      effectiveness (CE) ratios of the intervention were obtained for low birth weight
      (LBW) live births and stillbirths averted and cost per DALY saved. Cost per DALY
      saved was also estimated for previous CE studies of syphilis screening. The CE of
      the intervention at different syphilis prevalence rates was modelled. RESULTS:
      The economic cost of the intervention is $1.44 per woman screened, $20 per woman
      treated, and $187 per adverse birth outcome averted. The cost per DALY saved is
      $110 with LBW as the only adverse outcome. When including stillbirth, this
      estimate improves 10-fold to $10.56 per DALY saved. The cost per DALY saved from
      all syphilis screening studies ranged from $3.97 to $18.73. CONCLUSIONS: Syphilis
      screening is shown to be at least as cost effective as PMTCT and more cost
      effective than many widely implemented interventions. There is urgent need for
      scaling up syphilis screening and treatment in high prevalence areas. The CE of
      screening interventions is highly dependent on disease prevalence. In
      combination, PMTCT and syphilis screening and treatment interventions may achieve
      economies of scope and thus improved efficiency.

PMID- 14573833
TI  - Baseline survey of sexually transmitted infections in a cohort of female bar
      workers in Mbeya Region, Tanzania.
AB  - OBJECTIVES: To determine baseline prevalence of sexually transmitted infections
      (STI) and other reproductive tract infections (RTI) and their association with
      HIV as well as sociodemographic and behavioural characteristics in a newly
      recruited cohort of female bar workers in Mbeya Region, Tanzania. METHODS: 600
      female bar workers were recruited from 17 different communities during September
      to November 2000 and underwent gynaecological examination, laboratory testing for
      HIV/STI, and interviews using structured questionnaires. RESULTS: HIV-1
      seroprevalence was 68%. Prevalences of STI/RTI were high titre syphilis (TPPA/RPR
      >/=1/8), 9%; herpes simplex virus 2 antibodies, 87%; chlamydia, 12%; gonorrhoea,
      22%; trichomoniasis, 24%; and bacterial vaginosis, 40%. HIV infection was
      associated with TPPA and HSV-2 seropositivity, bacterial vaginosis and clinically
      diagnosed genital ulcers, blisters, and warts. Reported high risk sexual
      behaviour during the past year (having multiple casual partners) was associated
      with prevalent STI. CONCLUSION: Female bar workers in Mbeya are at high risk of
      STI and HIV infection. Targeted STI/HIV prevention interventions for these women
      and their sexual partners need to be reinforced. Methods should be sought to
      improve healthcare seeking and to provide easily accessible and affordable STI
      care services.

PMID- 14573834
TI  - Sexually transmitted infections in male clients of female sex workers in Benin:
      risk factors and reassessment of the leucocyte esterase dipstick for screening of
      urethral infections.
AB  - OBJECTIVES: (1) To assess risk factors for urethral infections with Chlamydia
      trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis among male clients
      of female sex workers (FSWs) in Benin; (2) to study the validity of LED testing
      of male urine samples compared to a highly sensitive gold standard (PCR) for the
      diagnosis of urethral infections with the organisms cited above. METHODS: Male
      clients of FSWs (n=404) were recruited on site at prostitution venues in Cotonou,
      Benin, between 28 May and 18 August 1998. A urine sample was obtained from each
      participant just before he visited the FSW, and tested immediately using a
      leucocyte esterase dipstick (LED) test. It was then tested for HIV using the
      Calypte EIA with western blot confirmation, and for C. trachomatis, N.
      gonorrhoeae, and T. vaginalis by PCR. After leaving the FSW's room, participants
      were interviewed about demographics, sexual behaviour, STI history and current
      symptoms and signs, and were examined for urethral discharge, genital ulcers, and
      inguinal lymphadenopathies. RESULTS: STI prevalences were: C. trachomatis, 2.7%;
      N. gonorrhoeae, 5.4%; either chlamydia or gonorrhoea 7.7%; T. vaginalis 2.7%;
      HIV, 8.4%. Lack of condom use with FSWs and a history of STI were independently
      associated with C. trachomatis and/or N. gonorrhoeae infection. Over 80% of these
      infections were in asymptomatic subjects. The overall sensitivity, specificity,
      positive and negative predictive values of the LED test for detection of either
      C. trachomatis or N. gonorrhoeae were 48.4%, 94.9%, 44.1%, and 95.7%,
      respectively. In symptomatic participants (n=22), all these parameters were 100%
      while they were 47.4%, 94.7%, 37.5%, and 96.4% in asymptomatic men (n=304).
      CONCLUSIONS: Since most STIs are asymptomatic in this population, case finding
      programmes for gonorrhoea and chlamydia could be useful. The performance
      characteristics of the LED test in this study suggest that it could be useful to
      detect asymptomatic infection by either C. trachomatis or N. gonorrhoeae in high
      risk men.

PMID- 14573835
TI  - Comparison of culture and different PCR assays for detection of Trichomonas
      vaginalis in self collected vaginal swab specimens.
AB  - OBJECTIVES: DNA amplification techniques have become widely used for the
      diagnosis of sexually transmitted infections. For the detection of Trichomonas
      vaginalis, PCR techniques are not yet widely used despite the publication of
      several assays. The sensitivity and specificity of five independent primer sets
      were determined on self collected vaginal specimens obtained from female
      commercial sex workers. METHODS: Self collected specimens were obtained from
      symptomatic and asymptomatic women attending a female sex workers clinic in
      Abidjan, Cote d'Ivoire. Two vaginal specimens were collected, the first one was
      processed for culture and the second was processed for PCR analysis. PCR
      techniques for trichomonads were performed, using the primers as reported by
      Riley (TVA5/TVA6), Kengne (TVK3/TVK7), Madico (BTUB 9/BTUB 2), Shiao (IP1/IP2),
      and Mayta (TV1/TV2). An EIA amplicon detection method was designed for each of
      the primer sets. RESULTS: True positive specimens were defined as culture
      positive and/or two positive PCR results with EIA amplicon detection in any
      combination. According to this definition a prevalence of 20% was obtained
      compared to 7% obtained by culture. The PCR primer set TVK3/TVK7 gave the highest
      sensitivity (89.2%). Poor sensitivities were obtained with the primer sets
      TV1/TV2 (60.2%) and TVA5/TVA6 (63.9%). PCR showed a sensitivity improvement of
      2.4% up to 12% when EIA was used for amplicon detection. CONCLUSIONS: Overall,
      the sensitivities of the different PCR assays resulting from this study were
      lower than those previously described. These findings could be the result of the
      nature of the specimen population and suggests a strain variability.

PMID- 14573836
TI  - Antimicrobial susceptibility of Neisseria gonorrhoeae strains isolated in
      Guangzhou, China, 1996-2001.
AB  - OBJECTIVE: To investigate the in vitro antimicrobial susceptibility and resistant
      trends of Neisseria gonorrhoeae strains isolated in Guangzhou, from 1996 to 2001.
      METHODS: The agar dilution method was used to determine the minimum inhibitory
      concentrations (MICs) to four antimicrobials, penicillin G, ciprofloxacin,
      ceftriaxone, and spectinomycin. The resistance of all strains to four antibiotics
      was interpreted according to criteria used in the project of surveillance of
      gonococcal antibiotic susceptibility in the WHO Western Pacific Region.
      Penicillinase producing N gonorrhoeae (PPNG) was analysed by the paper
      acidometric method. RESULTS: 793 consecutive N gonorrhoeae isolates collected in
      Guangzhou were studied from 1996 to 2001. A total of 55 strains of PPNG were
      identified and the prevalence rapidly spread from 2% to 21.8%. Of the four
      antibiotics examined, ceftriaxone and spectinomycin appeared to be the most
      effective agents although two spectinomycin resistant strains were isolated in
      1996. Their MIC(50), MIC(90), and geometric mean MIC (MICmean) were all between
      the sensitive ranges of the interpretative criteria and remained stable over the
      years. However, resistance increased continuously to penicillin G and
      dramatically to ciprofloxacin. In 1996-2001, MIC(50), MIC(90), and MICmean of
      penicillin G increased from 1 micro g/ml to 2 micro g/ml, 4 micro g/ml to 32
      micro g/ml, and 0.68 micro g/ml to 2.35 micro g/ml, respectively; those of
      ciprofloxacin steeply increased from 0.12 micro g/ml to 4 micro g/ml, 2 micro
      g/ml to 32 micro g/ml, and 0.14 micro g/ml to 2.62 micro g/ml in 1996-9,
      respectively, and then declined slightly in 2000-1. The prevalence of resistant
      isolates spread from 57.2% to 81.8% for penicillin G and from 17.6% to 72.7% for
      ciprofloxacin over the 6 years. CONCLUSION: Resistance to penicillin and
      ciprofloxacin increased greatly during 1996-2001. Ceftriaxone and spectinomycin
      should be used as the first line agents in treating gonorrhoea. It is of great
      importance to continuously survey the susceptibilities of N gonorrhoeae to
      antibiotics in controlling the spread of gonococcal infections.

PMID- 14573837
TI  - STD trends and patterns of treatment for STD by physicians in private practice in
      Peru.
AB  - OBJECTIVES: To describe trends in STD visits to physicians in private practice in
      Peru over a 15 year period and in the patterns of treatments used for STD.
      METHODS: IMS Health conducts for pharmaceutical marketing purposes surveys of a
      random cluster sample of 1.63% of practising physicians in Peru, stratified by
      region and specialty. Physicians record details of diagnoses and treatments for
      all patients seen during a 7 day period every 6 months. Data collected on
      selected STD syndromes were retrospectively reviewed over a 15 year period.
      RESULTS: The number of first visits for pelvic inflammatory disease (PID) and
      trichomoniasis, and total visits for genital herpes increased from 1983-5 to 1996
      7; while first visits for gonorrhoea and total visits for syphilis have changed
      little in recent years. Treatment for gonorrhoea usually involved the use of
      spectinomycin or an aminoglycoside only. Treatments offered for PID were
      remarkably inadequate and for trichomoniasis often involved products not known to
      be effective for trichomoniasis or other causes of vaginal discharge.
      CONCLUSIONS: This form of active surveillance provides information potentially
      useful to guide policies for prevention and management of STDs and HIV infections
      in developing countries.

PMID- 14573838
TI  - Adolescent women underestimate their susceptibility to sexually transmitted
      infections.
AB  - OBJECTIVES: Adolescent females are at significant risk for sexually transmitted
      infections (STI) and may not accurately incorporate indicators of risk into their
      perceptions of susceptibility. The objectives of the current analyses were to:
      (1) examine the relation between perceived susceptibility and indicators of risk;
      and (2) investigate the relation between perceived susceptibility and actual STI
      diagnosis. METHODS: Participants were 209 sexually active adolescent females.
      Indicators of STI risk included STI history, recent symptoms, and sexual risk
      behaviour (that is, recent unprotected sex and numbers of sexual partners).
      Chlamydia and gonorrhoea infection were assessed at baseline, 6, and 12 months
      post-baseline using urine based ligase chain reaction testing. RESULTS: Most
      participants perceived little or no chance that they would be diagnosed with an
      STI in the following year. There was no relation between almost all STI
      indicators and perceptions of susceptibility. Among those receiving a positive
      chlamydia or gonorrhoea test (n=49) at baseline or in the year following, almost
      all (81.3%) had perceived themselves to be at little or no risk. CONCLUSION: The
      adolescent females in this sample did not accurately perceive their
      susceptibility to STI. They must be enabled to more effectively assess and modify
      their risk.

PMID- 14573839
TI  - Risk factors leading to Cryptosporidium infection in men who have sex with men.
AB  - OBJECTIVES: Cryptosporidiosis is a devastating illness in people with HIV/AIDS
      yet there have been no analytical epidemiological studies measuring risk factors
      leading to cryptosporidiosis in men who have sex with men (MSM). The objective of
      this study was to measure the risk factors for exposure to Cryptosporidium among
      MSM. METHODS: The study was a case-control design. It recruited MSM who had
      laboratory confirmed Cryptosporidium infection between 1997 and 2000.
      Participants answered a questionnaire about potential risk factors leading to
      exposure to Cryptosporidium. RESULTS: 10 cases and 24 controls were recruited.
      Men having more than one sexual partner in the past month were more likely to
      have had Cryptosporidium diarrhoea p=0.034 (OR 6.67, CI (1.15 to 38.60).
      Insertive anal sex (p=0.059) and attending a sex venue one or more times
      (p=0.059) also increased the odds of having cryptosporidiosis. CONCLUSION: The
      study results suggest that sexual behaviour is a significant risk factor for
      cryptosporidial diarrhoea in MSM. The results will be used to inform risk groups
      about behaviours that may put them at increased risk of cryptosporidial
      diarrhoea.

PMID- 14573840
TI  - Treatment of neurosyphilis with ceftriaxone.
AB  - The first choice treatment for late syphilis is penicillin. Other than
      doxycycline, which penetrates the CNS, there are few alternatives for the
      treatment of neurosyphilis. We report a case of successful treatment of
      symptomatic neurosyphilis with parenteral ceftriaxone.

PMID- 14573841
TI  - Polymyositis masquerading as mitochondrial toxicity.
AB  - A 66 year old HIV infected male heavy smoker presented with arthralgia, myalgia,
      and weight loss which was originally ascribed to nucleoside induced mitochondrial
      toxicity. Despite withdrawal of antiretroviral therapy a proximal myopathy
      developed. Further investigation excluded malignancy. Polymyositis was diagnosed
      on muscle biopsy. The patient recovered completely with oral prednisolone. This
      case highlights the importance of muscle biopsy in HIV infected patients whose
      myopathy persists despite withdrawal of antiretroviral therapy and the need for
      thorough investigation of non-specific symptoms in HIV infected patients who are
      receiving antiretroviral therapy.

PMID- 14573842
TI  - Selective transmission of multidrug resistant HIV to a newborn related to poor
      maternal adherence.
AB  - OBJECTIVES: To report perinatal transmission of multidrug resistant (MDR) HIV
      related to variable maternal adherence antenatally. METHODS: Case study including
      review of clinic records, adherence information, laboratory data, and HIV
      genotyping results in mother and infant. RESULTS: Poor maternal adherence to
      clinic visits and antiretroviral therapy contributed to detectable viraemia
      antenatally. When tested for the first time at age 6 months, the infant was found
      to have virus with resistance to multiple drugs. In this case, prophylaxis with
      zidovudine (AZT) failed to prevent the transmission of the MDR strain.
      CONCLUSIONS: Perinatal transmission of MDR HIV can occur despite standard
      peripartum prophylaxis with AZT. Perinatal prophylaxis should be tailored to the
      mother's treatment history and resistance profile. Paediatric HIV specialists
      should be prepared to deal with a small, but slowly increasing number of babies
      with a "nightmare" multidrug resistant virus with limited treatment options.

PMID- 14573843
TI  - Chaperoning in genitourinary medicine clinics.

PMID- 14573844
TI  - Investigating the microbial aetiology of pelvic inflammatory disease.

PMID- 14573845
TI  - Perianal verrucous epidermal naevus mimicking perianal warts.

PMID- 14573846
TI  - Monosymptomatic hypochondriacal psychosis.

PMID- 14573847
TI  - Lack of evidence for sexual transmission of hepatitis C virus in patients
      attending STD clinics in Pune, India.

PMID- 14573848
TI  - Contamination of environmental surfaces by genital human papillomaviruses (HPV):
      a follow up study.

PMID- 14573849
TI  - A population based dynamic approach for estimating the cost effectiveness of
      screening for Chlamydia trachomatis.

PMID- 14573850
TI  - Issues associated with the introduction of circumcision into a non-circumcising
      society.

PMID- 14573851
TI  - Eyes wide open.

PMID- 14573852
TI  - Research on the brain.
AB  - Sponsored by the Movement Disorder Society, the 3rd International Workshop on
      Dementia with Lewy Bodies and Parkinson's Disease Dementia was held on 17 to 20
      September 2003 in Newcastle upon Tyne, United Kingdom. This meeting report
      summarizes findings presented at this meeting. The presentations focused on
      clinicopathological correlations, therapy, genetics, and basic science research.

PMID- 14573853
TI  - Organization and dynamics of tryptophan residues in erythroid spectrin: novel
      structural features of denatured spectrin revealed by the wavelength-selective
      fluorescence approach.
AB  - We have investigated the organization and dynamics of the functionally important
      tryptophan residues of erythroid spectrin in native and denatured conditions
      utilizing the wavelength-selective fluorescence approach. We observed a red edge
      excitation shift (REES) of 4 nm for the tryptophans in the case of spectrin in
      its native state. This indicates that tryptophans in spectrin are localized in a
      microenvironment of restricted mobility, and that the regions surrounding the
      spectrin tryptophans offer considerable restriction to the reorientational motion
      of the water dipoles around the excited state tryptophans. Interestingly,
      spectrin exhibits a REES of 3 nm even when denatured in 8 M urea. This represents
      the first report of a denatured protein displaying REES. Observation of REES in
      the denatured state implies that some of the structural and dynamic features of
      this microenvironment around the spectrin tryptophans are retained even when the
      protein is denatured. Fluorescence quenching data of denatured spectrin support
      this conclusion. In addition, we have deduced the organization and dynamics of
      the hydrophobic binding site of the polarity-sensitive fluorescent probe PRODAN
      that binds erythroid spectrin with high affinity. When bound to spectrin, PRODAN
      exhibits a REES of 9 nm. Because PRODAN binds to a hydrophobic site in spectrin,
      such a result would directly imply that this region of spectrin offers
      considerable restriction to the reorientational motion of the solvent dipoles
      around the excited state fluorophore. The results of our study could provide
      vital insight into the role of tryptophans in the stability and folding of
      spectrin.

PMID- 14573854
TI  - Protein self-association in solution: the bovine beta -lactoglobulin dimer and
      octamer.
AB  - We have used proton magnetic relaxation dispersion (MRD) to study the self
      association of bovine beta-lactoglobulin variant A (BLG-A) as a function of
      temperature at pH 4.7 (dimer-octamer equilibrium) and as a function of NaCl
      concentration at pH 2.5 (monomer-dimer equilibrium). The MRD method identifies
      coexisting oligomers from their rotational correlation times and determines their
      relative populations from the associated dispersion amplitudes. From MRD-derived
      correlation times and hydrodynamic model calculations, we confirm that BLG-A
      dimers associate to octamers below room temperature. The tendency for BLG-A
      dimers to assemble into octamers is found to be considerably weaker than in
      previous light scattering studies in the presence of buffer salt. At pH 2.5, the
      MRD data are consistent with an essentially complete transition from monomers in
      the absence of salt to dimers in 1 M NaCl. Because of an interfering relaxation
      dispersion from nanosecond water exchange, we cannot determine the oligomer
      populations at intermediate salt concentrations. This nanosecond dispersion may
      reflect intersite exchange of water molecules trapped inside the large binding
      cavity of BLG-A.

PMID- 14573855
TI  - Peptide models of four possible insulin folding intermediates with two
      disulfides.
AB  - The single-chain insulin (PIP) can spontaneously fold into native structure
      through preferred kinetic intermediates. During refolding, pairing of the first
      disulfide A20-B19 is highly specific, whereas pairing of the second disulfide is
      likely random because two two-disulfide intermediates have been trapped. To get
      more details of pairing property of the second disulfide, four model peptides of
      possible folding intermediates with two disulfides were prepared by protein
      engineering, and their properties were analyzed. The four model peptides were
      named [A20-B19, A7-B7]PIP, [A20-B19, A6-B7]PIP, [A20-B19, A6-A11]PIP, and [A20
      B19, A7-A11]PIP according to their remaining disulfides. The four model peptides
      all adopt partially folded structure with moderate conformational differences. In
      redox buffer, the disulfides of the model peptides are more easily reduced than
      those of the wild-type PIP. During in vitro refolding, the reduced model peptides
      share similar relative folding rates but different folding yields: The refolding
      efficiency of the reduced [A20-B19, A7-A11]PIP is about threefold lower than that
      of the other three peptides. The present results indicate that the folding
      intermediates corresponding to the present model peptides all adopt partially
      folded conformation, and can be formed during PIP refolding, but the chance of
      forming the intermediate with disulfide [A20-B19, A7-A11] is much lower than that
      of forming the other three intermediates.

PMID- 14573856
TI  - On the properties and sequence context of structurally ambivalent fragments in
      proteins.
AB  - The goal of this work is to characterize structurally ambivalent fragments in
      proteins. We have searched the Protein Data Bank and identified all structurally
      ambivalent peptides (SAPs) of length five or greater that exist in two different
      backbone conformations. The SAPs were classified in five distinct categories
      based on their structure. We propose a novel index that provides a quantitative
      measure of conformational variability of a sequence fragment. It measures the
      context-dependent width of the distribution of (phi,xi) dihedral angles
      associated with each amino acid type. This index was used to analyze the local
      structural propensity of both SAPs and the sequence fragments contiguous to them.
      We also analyzed type-specific amino acid composition, solvent accessibility, and
      overall structural properties of SAPs and their sequence context. We show that
      each type of SAP has an unusual, type-specific amino acid composition and, as a
      result, simultaneous intrinsic preferences for two distinct types of backbone
      conformation. All types of SAPs have lower sequence complexity than average.
      Fragments that adopt helical conformation in one protein and sheet conformation
      in another have the lowest sequence complexity and are sampled from a relatively
      limited repertoire of possible residue combinations. A statistically significant
      difference between two distinct conformations of the same SAP is observed not
      only in the overall structural properties of proteins harboring the SAP but also
      in the properties of its flanking regions and in the pattern of solvent
      accessibility. These results have implications for protein design and structure
      prediction.

PMID- 14573857
TI  - Identification of transglutaminase-mediated deamidation sites in a recombinant
      alpha-gliadin by advanced mass-spectrometric methodologies.
AB  - Celiac disease is a permanent immune-mediated food intolerance triggered by
      ingestion of wheat gliadins in genetically susceptible individuals. It has been
      reported that tissue transglutaminase plays an important role in the onset of
      celiac disease by converting specific glutamine residues within gliadin fragments
      into glutamic acid residues. This process increases binding affinity of gliadin
      peptides to HLA-DQ2/DQ8 molecules, thus enhancing the immune response. The aim of
      the present study was to achieve a detailed structural characterization of
      modifications induced by transglutaminase on gliadin peptides. Therefore,
      structural analyses were carried out on a recombinant alpha-gliadin and on a
      panel of 26 synthetic peptides, overlapping the complete protein sequence.
      Modified glutamine residues were identified by means of advanced mass
      spectrometric methodologies on the basis of MALDI-TOF-MS and tandem mass
      spectrometry. Results led to the identification of 19 of 94 glutamine residues
      present in the recombinant alpha-gliadin, which were converted into glutamic acid
      residues by a transglutaminase-mediated reaction. This allowed us to achieve a
      global view of the modifications induced by the enzyme on this protein.
      Furthermore, results gathered could likely be utilized as relevant information
      for a better understanding of processes leading to T-cell recognition of gliadin
      peptides involved in celiac disease.

PMID- 14573858
TI  - The geometry and efficacy of cation-pi interactions in a diagonal position of a
      designed beta-hairpin.
AB  - Cation-pi interactions are common in proteins, but their contribution to the
      stability and specificity of protein structure has not been well established. In
      this study, we examined the impact of cation-pi interactions in a diagonal
      position of a beta-hairpin peptide through comparison of the interaction of Phe
      or Trp with Lys or Arg. The diagonal interactions ranged from -0.20 to -0.48
      kcal/mole. Our experimental values for the diagonal cation-pi interactions are
      similar to those found in alpha-helical studies. Upfield shifting of the Lys and
      Arg side chains indicates that the geometries of cation-pi interactions adopted
      in the 12-residue beta-hairpin are comparable to those found in protein
      structures. The Lys was found to interact through the polarized Cepsilon, and the
      Arg is stacked against the aromatic ring of Phe or Trp. Folding of these peptides
      was found to be enthalpically favorable (DeltaH degrees equals approximately -3
      kcal/mole) and entropically unfavorable (DeltaS degrees equals approximately -8
      cal mole(-1) K(-1)).

PMID- 14573860
TI  - Self-assembly of single integral membrane proteins into soluble nanoscale
      phospholipid bilayers.
AB  - One of the biggest challenges in pharmaceutical research is obtaining integral
      membrane proteins in a functional, solubilized, and monodisperse state that
      provides a native-like environment that maintains the spectrum of in vivo
      activities. Many of these integral membrane proteins are receptors, enzymes, or
      other macromolecular assemblies that are important drug targets. An example is
      the general class of proteins composed of seven-transmembrane segments (7-TM) as
      exemplified by the G-protein-coupled receptors. In this article, we describe a
      simple system for self-assembling bacteriorhodopsin, as a model protein
      containing 7-TM helices, with phospholipids to form a nanometer-scale soluble
      bilayer structure encircled by a 200 amino acid scaffold protein. The result is
      the single molecule incorporation of an integral membrane protein target into a
      soluble and monodisperse structure that allows the structural and functional
      tools of solution biochemistry to be applied.

PMID- 14573859
TI  - Constraints on the conformation of the cytoplasmic face of dark-adapted and light
      excited rhodopsin inferred from antirhodopsin antibody imprints.
AB  - Rhodopsin is the best-understood member of the large G protein-coupled receptor
      (GPCR) superfamily. The G-protein amplification cascade is triggered by poorly
      understood light-induced conformational changes in rhodopsin that are homologous
      to changes caused by agonists in other GPCRs. We have applied the "antibody
      imprint" method to light-activated rhodopsin in native membranes by using nine
      monoclonal antibodies (mAbs) against aqueous faces of rhodopsin. Epitopes
      recognized by these mAbs were found by selection from random peptide libraries
      displayed on phage. A new computer algorithm, FINDMAP, was used to map the
      epitopes to discontinuous segments of rhodopsin that are distant in the primary
      sequence but are in close spatial proximity in the structure. The proximity of a
      segment of the N-terminal and the loop between helices VI and VIII found by
      FINDMAP is consistent with the X-ray structure of the dark-adapted rhodopsin.
      Epitopes to the cytoplasmic face segregated into two classes with different
      predicted spatial proximities of protein segments that correlate with different
      preferences of the antibodies for stabilizing the metarhodopsin I or
      metarhodopsin II conformations of light-excited rhodopsin. Epitopes of antibodies
      that stabilize metarhodopsin II indicate conformational changes from dark-adapted
      rhodopsin, including rearrangements of the C-terminal tail and altered exposure
      of the cytoplasmic end of helix VI, a portion of the C-3 loop, and helix VIII. As
      additional antibodies are subjected to antibody imprinting, this approach should
      provide increasingly detailed information on the conformation of light-excited
      rhodopsin and be applicable to structural studies of other challenging protein
      targets.

PMID- 14573861
TI  - Soluble mimics of a chemokine receptor: chemokine binding by receptor elements
      juxtaposed on a soluble scaffold.
AB  - Despite the broad biological importance of G protein-coupled receptors (GPCRs),
      ligand recognition by GPCRs remains poorly understood. To explore the roles of
      GPCR extracellular elements in ligand binding and to provide a tractable system
      for structural analyses of GPCR/ligand interactions, we have developed a soluble
      protein that mimics ligand recognition by a GPCR. This receptor analog, dubbed
      CROSS5, consists of the N-terminal and third extracellular loop regions of CC
      chemokine receptor 3 (CCR3) displayed on the surface of a small soluble protein,
      the B1 domain of Streptococcal protein G. CROSS5 binds to the CCR3 ligand eotaxin
      with a dissociation equilibrium constant of 2.9 +/- 0.8 microM and competes with
      CCR3 for eotaxin binding. Control proteins indicate that juxtaposition of both
      CCR3 elements is required for optimal binding to eotaxin. Moreover, the
      affinities of CROSS5 for a series of eotaxin mutants are highly correlated with
      the apparent affinities of CCR3 for the same mutants, demonstrating that CROSS5
      uses many of the same interactions as does the native receptor. The strategy used
      to develop CROSS5 could be applied to many other GPCRs, with a variety of
      potential applications.

PMID- 14573862
TI  - Multiple structural alignment by secondary structures: algorithm and
      applications.
AB  - We present MASS (Multiple Alignment by Secondary Structures), a novel highly
      efficient method for structural alignment of multiple protein molecules and
      detection of common structural motifs. MASS is based on a two-level alignment,
      using both secondary structure and atomic representation. Utilizing secondary
      structure information aids in filtering out noisy solutions and achieves
      efficiency and robustness. Currently, only a few methods are available for
      addressing the multiple structural alignment task. In addition to using secondary
      structure information, the advantage of MASS as compared to these methods is that
      it is a combination of several important characteristics: (1) While most existing
      methods are based on series of pairwise comparisons, and thus might miss optimal
      global solutions, MASS is truly multiple, considering all the molecules
      simultaneously; (2) MASS is sequence order-independent and thus capable of
      detecting nontopological structural motifs; (3) MASS is able to detect not only
      structural motifs, shared by all input molecules, but also motifs shared only by
      subsets of the molecules. Here, we show the application of MASS to various
      protein ensembles. We demonstrate its ability to handle a large number (order of
      tens) of molecules, to detect nontopological motifs and to find biologically
      meaningful alignments within nonpredefined subsets of the input. In particular,
      we show how by using conserved structural motifs, one can guide protein-protein
      docking, which is a notoriously difficult problem. MASS is freely available at
      http://bioinfo3d.cs.tau.ac.il/MASS/.

PMID- 14573863
TI  - Revisiting the Ramachandran plot: hard-sphere repulsion, electrostatics, and H
      bonding in the alpha-helix.
AB  - What determines the shape of the allowed regions in the Ramachandran plot?
      Although Ramachandran explained these regions in terms of 1-4 hard-sphere
      repulsions, there are discrepancies with the data where, in particular, the
      alphaR, alphaL, and beta-strand regions are diagonal. The alphaR-region also
      varies along the alpha-helix where it is constrained at the center and the amino
      terminus but diffuse at the carboxyl terminus. By analyzing a high-resolution
      database of protein structures, we find that certain 1-4 hard-sphere repulsions
      in the standard steric map of Ramachandran do not affect the statistical
      distributions. By ignoring these steric clashes (NH(i+1) and O(i-1)C), we
      identify a revised set of steric clashes (CbetaO, O(i-1)N(i+1), CbetaN(i+1), O(i
      1)Cbeta, and O(i-1)O) that produce a better match with the data. We also find
      that the strictly forbidden region in the Ramachandran plot is excluded by
      multiple steric clashes, whereas the outlier region is excluded by only one
      significant steric clash. However, steric clashes alone do not account for the
      diagonal regions. Using electrostatics to analyze the conformational dependence
      of specific interatomic interactions, we find that the diagonal shape of the
      alphaR and alphaL-regions also depends on the optimization of the NH(i+1) and O(i
      1)C interactions, and the diagonal beta-strand region is due to the alignment of
      the CO and NH dipoles. Finally, we reproduce the variation of the Ramachandran
      plot along the alpha-helix in a simple model that uses only H-bonding
      constraints. This allows us to rationalize the difference between the amino
      terminus and the carboxyl terminus of the alpha-helix in terms of backbone
      entropy.

PMID- 14573864
TI  - Allosteric transition pathways in the lactose repressor protein core domains:
      asymmetric motions in a homodimer.
AB  - The crystal structures of lactose repressor protein (LacI) provide static
      endpoint views of the allosteric transition between DNA- and IPTG-bound states.
      To obtain an atom-by-atom description of the pathway between these two
      conformations, motions were simulated with targeted molecular dynamics (TMD).
      Strikingly, this homodimer exhibited asymmetric dynamics. All asymmetries
      observed in this simulation are reproducible and can begin on either of the two
      monomers. Asymmetry in the simulation originates around D149 and was traced back
      to the pre-TMD equilibrations of both conformations. In particular, hydrogen
      bonds between D149 and S193 adopt a variety of configurations during repetitions
      of this process. Changes in this region propagate through the structure via
      noncovalent interactions of three interconnected pathways. The changes of pathway
      1 occur first on one monomer. Alterations move from the inducer-binding pocket,
      through the N-subdomain beta-sheet, to a hydrophobic cluster at the top of this
      region and then to the same cluster on the second monomer. These motions result
      in changes at (1) side chains that form an interface with the DNA-binding domains
      and (2) K84 and K84', which participate in the monomer-monomer interface. Pathway
      2 reflects consequent reorganization across this subunit interface, most notably
      formation of a H74-H74rsquo; pi-stacking intermediate. Pathway 3 extends from the
      rear of the inducer-binding pocket, across a hydrogen-bond network at the bottom
      of the pocket, and transverses the monomer-monomer interface via changes in H74
      and H74rsquo;. In general, intermediates detected in this study are not apparent
      in the crystal structures. Observations from the simulations are in good
      agreement with biochemical data and provide a spatial and sequential framework
      for interpreting existing genetic data.

PMID- 14573865
TI  - Free-energy landscape of a chameleon sequence in explicit water and its inherent
      alpha/beta bifacial property.
AB  - A sequence in yeast MATalpha2/MCM1/DNA complex that folds into alpha-helix or
      beta-hairpin depending on the surroundings has been known as "chameleon"
      sequence. We obtained the free-energy landscape of this sequence by using a
      generalized-ensemble method, multicanonical molecular dynamics simulation, to
      sample the conformational space. The system was expressed with an all-atom model
      in explicit water, and the initial conformation for the simulation was a random
      one. The free-energy landscape demonstrated that this sequence inherently has an
      ability to form either alpha or beta structure: The conformational distribution
      in the landscape consisted of two alpha-helical clusters with different packing
      patterns of hydrophobic residues, and four beta-hairpin clusters with different
      strand-strand interaction patterns. Narrow pathways connecting the clusters were
      found, and analysis on the pathways showed that a compact structure formed at the
      N-terminal root of the chameleon sequence controls the cluster-cluster
      transitions. The free-energy landscape indicates that a small conditional change
      induces alpha-beta transitions. Additional unfolding simulations done with
      replacing amino acids showed that the chameleon sequence has an advantage to form
      an alpha-helix. Current study may be useful to understand the mechanism of
      diseases resulting from abnormal chain folding, such as amyloid disease.

PMID- 14573866
TI  - Modulating the binding properties of an anti-17beta-estradiol antibody by
      systematic mutation combinations.
AB  - The anti-17beta-estradiol antibody 57-2 has been a subject for several protein
      engineering studies that have produced a number of mutants with improved binding
      properties. Here, we generated a set of 16 antibody 57-2 variants by
      systematically combining mutations previously identified from phage display
      derived improved antibody mutants. These mutations included three point mutations
      in the variable domain of the light-chain and a heavy-chain variant containing a
      four-residue random insertion in complementarity determining region CDR-H2. The
      antibody variants were expressed as Fab fragments, and they were characterized
      for affinity toward estradiol, for cross-reactivity toward three related
      steroids, and for dissociation rate of the Fab/estradiol complex by using time
      resolved fluorescence based immunoassays. The double-mutant cycle method was used
      to address the cooperativity effects between the mutations. The experimental data
      were correlated with structural information by using molecular modeling and
      visual analysis of the previously solved antibody 57-2 crystal structures. These
      analyses provided information about the steroid-binding mode of the antibody, the
      potential mechanisms of individual mutations, and their mutual interactions.
      Furthermore, several combinatorial mutants with improved affinity and specificity
      were obtained. The capacity of one of these mutants to detect estradiol
      concentrations at a clinically relevant range was proved by establishing a time
      resolved fluorescence based immunoassay.

PMID- 14573867
TI  - High-resolution crystal structures of ribonuclease A complexed with adenylic and
      uridylic nucleotide inhibitors. Implications for structure-based design of
      ribonucleolytic inhibitors.
AB  - The crystal structures of bovine pancreatic ribonuclease A (RNase A) in complex
      with 3',5'-ADP, 2',5'-ADP, 5'-ADP, U-2'-p and U-3'-p have been determined at high
      resolution. The structures reveal that each inhibitor binds differently in the
      RNase A active site by anchoring a phosphate group in subsite P1. The most potent
      inhibitor of all five, 5'-ADP (Ki = 1.2 microM), adopts a syn conformation (in
      contrast to 3',5'-ADP and 2',5'-ADP, which adopt an anti), and it is the beta-
      rather than the alpha-phosphate group that binds to P1. 3',5'-ADP binds with the
      5'-phosphate group in P1 and the adenosine in the B2 pocket. Two different
      binding modes are observed in the two RNase A molecules of the asymmetric unit
      for 2',5'-ADP. This inhibitor binds with either the 3' or the 5' phosphate groups
      in subsite P1, and in each case, the adenosine binds in two different positions
      within the B2 subsite. The two uridilyl inhibitors bind similarly with the
      uridine moiety in the B1 subsite but the placement of a different phosphate group
      in P1 (2' versus 3') has significant implications on their potency against RNase
      A. Comparative structural analysis of the RNase A, eosinophil-derived neurotoxin
      (EDN), eosinophil cationic protein (ECP), and human angiogenin (Ang) complexes
      with these and other phosphonucleotide inhibitors provides a wealth of
      information for structure-based design of inhibitors specific for each RNase.
      These inhibitors could be developed to therapeutic agents that could control the
      biological activities of EDN, ECP, and ANG, which play key roles in human
      pathologies.

PMID- 14573868
TI  - Monobromobimane occupies a distinct xenobiotic substrate site in glutathione S
      transferase pi.
AB  - Monobromobimane (mBBr), functions as a substrate of porcine glutathione S
      transferase pi (GST pi): The enzyme catalyzes the reaction of mBBr with
      glutathione. S-(Hydroxyethyl)bimane, a nonreactive analog of monobromobimane,
      acts as a competitive inhibitor with respect to mBBr as substrate but does not
      affect the reaction of GST pi with another substrate, 1-chloro-2,4-dinitrobenzene
      (CDNB). In the absence of glutathione, monobromobimane inactivates GST pi at pH
      7.0 and 25 degrees C as assayed using mBBr as substrate, with a lesser effect on
      the enzyme's use of CDNB as substrate. These results indicate that the sites
      occupied by CDNB and mBBr are not identical. Inactivation is proportional to the
      incorporation of 2 moles of bimane/mole of subunit. Modification of GST pi with
      mBBr does not interfere with its binding of 8-anilino-1-naphthalene sulfonate,
      indicating that this hydrophobic site is not the target of monobromobimane. S
      Methylglutathione and S-(hydroxyethyl)bimane each yield partial protection
      against inactivation and decrease reagent incorporation, while glutathionyl
      bimane protects completely against inactivation. Peptide analysis after trypsin
      digestion indicates that mBBr modifies Cys45 and Cys99 equally. Modification of
      Cys45 is reduced in the presence of S-methylglutathione, indicating that this
      residue is at or near the glutathione binding region. In contrast, modification
      of Cys99 is reduced in the presence of S-(hydroxyethyl)bimane, suggesting that
      this residue is at or near the mBBr xenobiotic substrate binding site.
      Modification of Cys99 can best be understood by reaction with monobromobimane
      while it is bound to its xenobiotic substrate site in an alternate orientation.
      These results support the concept that glutathione S-transferase accomplishes its
      ability to react with a diversity of substrates in part by harboring distinct
      xenobiotic substrate sites.

PMID- 14573869
TI  - The solution structure of the bacterial HSP70 chaperone protein domain DnaK(393
      507) in complex with the peptide NRLLLTG.
AB  - The Hsp70 family of molecular chaperones participates in a number of cellular
      processes, including binding to nascent polypeptide chains and assistance in
      protein (re)folding and degradation. We present the solution structure of the
      substrate binding domain (residues 393-507) of the Escherichia coli Hsp70, DnaK,
      that is bound to the peptide NRLLLTG and compare it to the crystal structure of
      DnaK(389-607) bound to the same peptide. The construct discussed here does not
      contain the alpha-helical domain that characterizes earlier published peptide
      bound structures of the Hsp70s. It is established that removing the alpha-helical
      domain in its entirety does not affect the primary interactions or structure of
      the DnaK(393-507) in complex with the peptide NRLLLTG. In particular, the arch
      that protects the substrate-binding cleft is also formed in the absence of the
      helical lid. 15N-relaxation measurements show that the peptide-bound form of
      DnaK(393-507) is relatively rigid. As compared to the peptide-free state, the
      peptide-bound state of the domain shows distinct, widespread, and contiguous
      differences in structure extending toward areas previously defined as important
      to the allosteric regulation of the Hsp70 chaperones.

PMID- 14573870
TI  - Initial structural and dynamic characterization of the M2 protein transmembrane
      and amphipathic helices in lipid bilayers.
AB  - Amphipathic helices in membrane proteins that interact with the
      hydrophobic/hydrophilic interface of the lipid bilayer have been difficult to
      structurally characterize. Here, the backbone structure and orientation of an
      amphipathic helix in the full-length M2 protein from influenza A virus has been
      characterized. The protein has been studied in hydrated DMPC/DMPG lipid bilayers
      above the gel to liquid-crystalline phase transition temperature by solid-state
      NMR spectroscopy. Characteristic PISA (Polar Index Slant Angle) wheels reflecting
      helical wheels have been observed in uniformly aligned bilayer preparations of
      both uniformly 15N labeled and amino acid specific labeled M2 samples.
      Hydrogen/deuterium exchange studies have shown the very slow exchange of some
      residues in the amphipathic helix and more rapid exchange for the transmembrane
      helix. These latter results clearly suggest the presence of an aqueous pore. A
      variation in exchange rate about the transmembrane helical axis provides
      additional support for this claim and suggests that motions occur about the
      helical axes in this tetramer to expose the entire backbone to the pore.

PMID- 14573871
TI  - Crystal structure of truncated human betaB1-crystallin.
AB  - Crystallins are long-lived proteins packed inside eye lens fiber cells that are
      essential in maintaining the transparency and refractive power of the eye lens.
      Members of the two-domain betagamma-crystallin family assemble into an array of
      oligomer sizes, forming intricate higher-order networks in the lens cell. Here we
      describe the 1.4 angstroms resolution crystal structure of a truncated version of
      human betaB1 that resembles an in vivo age-related truncation. The structure
      shows that unlike its close homolog, betaB2-crystallin, the homodimer is not
      domain swapped, but its domains are paired intramolecularly, as in more distantly
      related monomeric gamma-crystallins. However, the four-domain dimer resembles one
      half of the crystallographic bovine betaB2 tetramer and is similar to the
      engineered circular permuted rat betaB2. The crystal structure shows that the
      truncated betaB1 dimer is extremely well suited to form higher-order lattice
      interactions using its hydrophobic surface patches, linker regions, and sequence
      extensions.

PMID- 14573872
TI  - Solution structure and function of an essential CMP kinase of Streptococcus
      pneumoniae.
AB  - Streptococcus pneumoniae is a major human pathogen that causes high mortality and
      morbidity and has developed resistance to many antibiotics. We show that the gene
      product from SP1603, identified from S. pneumoniae TIGR4, is a CMP kinase that is
      essential for bacterial growth. It represents an attractive drug target for the
      development of a novel antibiotic to overcome the problems of drug resistance
      development for this organism. Here we describe the three-dimensional solution
      structure of the S. pneumoniae CMP kinase as determined by NMR spectroscopy. The
      structure consists of eight alpha-helices and two beta-sheets that fold into the
      classical core domain, the substrate-binding domain, and the LID domain. The
      three domains of the protein pack together to form a central cavity for substrate
      binding and enzymatic catalysis. The S. pneumoniae CMP kinase resembles the fold
      of the Escherichia coli homolog. An insertion of one residue is observed at the
      beta-turn in the substrate-binding domain of the S. pneumoniae CMP kinase when
      compared with the E. coli homolog. Chemical shift perturbations caused by the
      binding of CMP, CDP, and ATP revealed that CMP or CDP binds to the junction
      between the core and substrate-binding domains, whereas ATP binds to the junction
      between the core and LID domains. From NMR relaxation studies, we determined that
      the loops in the LID domain are highly mobile. These mobile loops could aid in
      the closing/opening of the LID domain during enzyme catalysis.

PMID- 14573874
TI  - H-bonding mediates polarization of peptide groups in folded proteins.
AB  - The carbon-nitrogen J-couplings in the hydrogen bonding chains of proteins show
      that H-bonding mediates peptide-group polarization, which results in the general
      reduction of peptide-group polarity of folded proteins in solution. The net
      effect is to make large regions of protein secondary structure, especially beta
      sheets, intrinsically more hydrophobic, contributing thereby to overall stability
      of the tertiary structure.

PMID- 14573875
TI  - Chemical modification of insulin in amyloid fibrils.
AB  - We have investigated the chemical modification of insulin under conditions that
      promote the conversion of the soluble protein into amyloid fibrils. The
      modifications that are incorporated into the fibrils include deamidation of Asn
      A21, Asn B3, and Gln B4. In order to prepare fibrils with minimal deamidation of
      these residues, the kinetics of aggregation were accelerated by seeding with
      aliquots of a solution containing preformed fibrils. The resulting fibrils were
      then reincubated to determine the extent to which chemical modification occurs in
      the fibril itself. The deamidation of Asn A21 in particular could be followed in
      detail. Deamidation of this residue in the fibrillar form of insulin was found to
      occur in only 52 +/- 5% of molecules. This result indicates that there are at
      least two different packing environments of insulin molecules in the fibrils and
      suggests that the characterization of chemical modifications may be a useful
      probe of the environment of polypeptide chains within amyloid fibrils.

PMID- 14573873
TI  - Structure and stability of the ankyrin domain of the Drosophila Notch receptor.
AB  - The Notch receptor contains a conserved ankyrin repeat domain that is required
      for Notch-mediated signal transduction. The ankyrin domain of Drosophila Notch
      contains six ankyrin sequence repeats previously identified as closely matching
      the ankyrin repeat consensus sequence, and a putative seventh C-terminal sequence
      repeat that exhibits lower similarity to the consensus sequence. To better
      understand the role of the Notch ankyrin domain in Notch-mediated signaling and
      to examine how structure is distributed among the seven ankyrin sequence repeats,
      we have determined the crystal structure of this domain to 2.0 angstroms
      resolution. The seventh, C-terminal, ankyrin sequence repeat adopts a regular
      ankyrin fold, but the first, N-terminal ankyrin repeat, which contains a 15
      residue insertion, appears to be largely disordered. The structure reveals a
      substantial interface between ankyrin polypeptides, showing a high degree of
      shape and charge complementarity, which may be related to homotypic interactions
      suggested from indirect studies. However, the Notch ankyrin domain remains
      largely monomeric in solution, demonstrating that this interface alone is not
      sufficient to promote tight association. Using the structure, we have classified
      reported mutations within the Notch ankyrin domain that are known to disrupt
      signaling into those that affect buried residues and those restricted to surface
      residues. We show that the buried substitutions greatly decrease protein
      stability, whereas the surface substitutions have only a marginal affect on
      stability. The surface substitutions are thus likely to interfere with Notch
      signaling by disrupting specific Notch-effector interactions and map the sites of
      these interactions.

PMID- 14573876
TI  - Recombinant extracellular domain of the three major subunits of GABAA receptor
      show comparable secondary structure and benzodiazepine binding properties.
AB  - The three most widely expressed subunits of the GABAA receptor are alpha(1),
      beta(2), and gamma(2) subunits, and the major isoform in the human brain is a
      pentameric receptor composed of 2alpha(1)2beta(2)1gamma(2). Previously, we
      overexpressed the extracellular domain Q28-R248 of GABAA receptor alpha(1)
      subunit. In the present study, the homologous extracellular domains Q25-G243 of
      GABAA receptor beta(2) subunit and Q40-G273 of gamma(2) subunit were also
      obtained through overexpression in Escherichia coli. Successful production of
      recombinant beta(2) and gamma(2) subunit receptor protein domains facilitates the
      comparison of structural and functional properties of the three subunits. To this
      end, the secondary structures of the three fragments were measured using CD
      spectroscopy and the beta-strand contents calculated to be >30%, indicating a
      beta-rich structure for all three fragments. In addition, the benzodiazepine (BZ)
      binding affinity of the recombinant fragments were measured using fluorescence
      polarization to be 2.16 microM, 3.63 microM, and 1.34 microM for the alpha(1),
      beta(2), and gamma(2) subunit fragments, respectively, indicating that all three
      homomeric assemblies, including that of the beta(2) subunit, generally not
      associated with BZ binding, can bind BZ in the micromolar range. The finding that
      the BZ binding affinity of these recombinant domains was highest for the gamma(2)
      subunit and lowest for the beta(2) subunit is consistent with results from
      previous binding studies using hetero-oligomeric receptors. The present results
      exemplify the effective approach to characterize and compare the three major
      subunits of the GABAA receptor, for two of which the overexpression in E. coli is
      reported for the first time.

PMID- 14573877
TI  - Modern analytical ultracentrifugation in protein science: look forward, not back.
AB  - The reasons for replacing the classical strictly two-component velocity and
      equilibrium analytical ultracentrifugation Svedberg equations by multicomponent
      equations, applicable in the study of biological macromolecular systems, are
      given.

PMID- 14573880
TI  - Obstructive sarcoidosis.
AB  - Sarcoidosis is a systemic granulomatous disease that frequently involves the
      lung. Although classically thought of as a restrictive lung disease, airway
      obstruction has become a recognized feature of the disease in the past years.
      Sarcoidosis can affect the airway at any level and when the involvement includes
      small airways, it can resemble more common obstructive airway diseases, such as
      asthma and chronic bronchitis. Pulmonary function testing and high-resolution
      computerized tomography of the chest are two important tools to evaluate the
      presence and extent of airway obstruction in sarcoidosis. Pharmacologic options
      for the treatment of obstructive sarcoidosis are, in large part, not supported by
      large, randomized clinical trials. In severe cases of bronchostenosis owing to
      sarcoidosis granuloma or extrinsic compression from intrathoracic
      lymphadenopathy, interventional bronchoscopy has successfully been performed,
      although repeated procedures are usually required. Lung transplantation is an
      ultimate option in selected patients with late-stage fibrotic disease.

PMID- 14573883
TI  - Surgery for severe rhinosinusitis.
AB  - Sinusitis is one of the most common reasons patients visit their primary care
      physician. The etiology of sinusitis is multifactorial in most cases. However,
      the final common pathway of disruption is usually made with a thorough history.
      The physical examination is often unremarkable. Complaints of nasal obstruction,
      mucopuluent nasal drainage, and facial pain/pressure are most diagnostic chronic
      sinusitis. Isolated headache is an uncommon presenting symptom. Computed
      tomography scans are the gold standard for diagnostic imaging. They can be used
      both for diagnosis and surgical treatment. All chronic sinusitis patients, being
      considered for endoscopic sinus surgery, should have failed a trial of maximal
      medical therapy. This includes a 4-6 wk course of oral antibiotics, nasal
      steroids, topical nasal decongestants, and oral prednisone if possible. Patients
      who fail maximal medical therapy have persistent symptoms that significantly
      effect their daily activities, have chronic abnormalities on computed tomography
      scan, and are candidates for endoscopic sinus surgery. Appropriate patient
      selection and preoperative counseling are key factors in patient satisfaction.
      Most patients with symptoms that significantly impact their daily activities will
      receive marked improvement in symptoms after sinus surgery. Endoscopic sinus
      surgery has undergone radical changes in the last 15 yr. Minimally invasive
      techniques, combined with advances in instrumentation and computers have reduced
      postoperative discomfort and improved patient satisfaction.

PMID- 14573881
TI  - Severe asthma.
AB  - Severe asthma is a term that is commonly used to describe patients with
      refractory, brittle, near fatal, and difficult-to-control asthma. Patients with
      severe asthma typically experience persistent symptoms despite medical therapy,
      report decreased quality of life and suffer an accelerated loss of lung function.
      The role of genetics, environmental exposure, and infection in the development of
      more severe asthma is the focus of ongoing research. While pathologic changes in
      these patients are now believed to involve lung parenchyma, in addition to large
      and small airways, the independent contribution of each of these compartments to
      the severe asthma phenotype is not well defined. The clinical evaluation of
      severe asthma patients should include investigating conditions commonly
      associated with severe asthma, such as gastroesophageal reflux disease, vocal
      cord dysfunction, and rhinosinusitis. In addition, advanced imaging techniques,
      measurement of exhaled gas or sputum indices, and airway biopsy are tools that
      may aid in evaluating severe asthma patients in the near future. Management of
      patients with severe asthma requires a comprehensive approach that includes non
      pharmacological and pharmacological measures. Combination antiinflammatory and
      long-acting bronchodilator therapy remains the mainstay of management.

PMID- 14573882
TI  - Severe chronic obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) exacts a heavy toll on society, yet
      its prevention, diagnosis and treatment receives inadequate attention from both
      the medical community and from society at large. Guidelines released in 2001 from
      the Global Initiative for Chronic Obstructive Lung Disease (GOLD) are aimed at
      redressing this inequity. In this review, we integrate information from the GOLD
      guidelines with recent updates on the prevention, treatment and management as
      related specifically to the most severe form of this disease. In order to help
      distinguish COPD from other disorders that may mimic or confound its treatment,
      we place particular emphasis on the definition, underlying pathophysiology and
      diagnosis of COPD. In addition, we discuss future directions in pharmacotherapy.

PMID- 14573884
TI  - Severe rhinosinusitis.
AB  - Rhinosinusitis is diagnosed frequently in clinical practice, but the term may in
      fact encompass a wide spectrum of diseases. Inflammation of the nasal and sinus
      mucosa can arise from various causes and lead to different sequelae. Moreover,
      the term rhinosinusitis is more accurate than sinusitis. Causes range from a
      viral infection leading to the common cold to an invasive, fungal infection. An
      accurate diagnosis is important because effective therapy is available if
      recognized early and if specific therapy is used. Importantly, there is a close
      relationship between upper and lower airway disease and each have unique
      structural and functional differences that make an understanding of
      rhinosinusitis important not only for upper airway disease, but also for the
      management of asthma. All too often, rhinosinusitis becomes chronic and this
      becomes a challenge because medical therapy may not be sufficient to control
      disease. Finally, we should note that the differential diagnosis of
      rhinosinusitis is extensive and physicians should place heavy emphasis not only
      on the history, but also on appropriate imaging studies. A normal exam does not
      rule out the possibility of rhinosinusitis. Finally, we should emphasize that
      effective treatment is dependent on the etiology of the symptoms but also
      dependent on whether it is acute or chronic.

PMID- 14573886
TI  - Large-scale generation of plasmids that express type I interferon.

PMID- 14573887
TI  - Identification of trans-acting factors by electrophoretic mobility shift assay.

PMID- 14573888
TI  - Modulation of the interferon-gamma signal by transfection of cells with an
      antisense-RNA expressing vector.

PMID- 14573885
TI  - Severe upper airway obstruction during sleep.
AB  - Few disorders may manifest with predominantly sleep-related obstructive
      breathing. Obstructive sleep apnea (OSA) is a common disorder, varies in severity
      and is associated with significant cardiovascular and neurocognitive morbidity.
      It is estimated that between 8 and 18 million people in the United States have at
      least mild OSA. Although the exact mechanism of OSA is not well-delineated,
      multiple factors contribute to the development of upper airway obstruction and
      include anatomic, mechanical, neurologic, and inflammatory changes in the
      pharynx. OSA may occur concomitantly with asthma. Approximately 74% of asthmatics
      experience nocturnal symptoms of airflow obstruction secondary to reactive
      airways disease. Similar cytokine, chemokine, and histologic changes are seen in
      both disorders. Sleep deprivation, chronic upper airway edema, and inflammation
      associated with OSA may further exacerbate nocturnal asthma symptoms. Allergic
      rhinitis may contribute to both OSA and asthma. Continuous positive airway
      pressure (CPAP) is the gold standard treatment for OSA. Treatment with CPAP
      therapy has also been shown to improve both daytime and nighttime peak expiratory
      flow rates in patients with concomitant OSA and asthma. It is important for
      allergists to be aware of how OSA may complicate diagnosis and treatment of
      asthma and allergic rhinitis. A thorough sleep history and high clinical
      suspicion for OSA is indicated, particularly in asthma patients who are
      refractory to standard medication treatments.

PMID- 14573889
TI  - Competitive RT-PCR to quantify small amounts of mRNA.

PMID- 14573890
TI  - In situ hybridization for cytokines in human tissue biopsies.

PMID- 14573891
TI  - Purification, identification, and synthesis of chemokines.

PMID- 14573892
TI  - Receptor isolation and characterization: from protein to gene.

PMID- 14573893
TI  - Crystallization of cytokine-receptor complexes.

PMID- 14573894
TI  - Biosensor analysis of receptor-ligand interactions.

PMID- 14573895
TI  - Analysis of SH2 ligands and identification of sites of interaction.

PMID- 14573896
TI  - Assays for antiviral activity.

PMID- 14573897
TI  - Assays for cytotoxicity.

PMID- 14573898
TI  - Assays for chemotaxis.

PMID- 14573899
TI  - In vitro and in vivo assays for high-molecular-weight pegylated muteins of
      granulocyte colony-stimulating factor.

PMID- 14573900
TI  - Development of a mammalian Tet-on expression cell line: glucosylceramide synthase
      regulates TNF-alpha-induced apoptosis.

PMID- 14573901
TI  - Immunohistochemical detection of cytokines in human tissue sections.

PMID- 14573902
TI  - Detection of cytokine- and chemokine-expressing cells at the single cell level.

PMID- 14573903
TI  - Detection of cytokine signal transduction "cross-talk" in leukocyte activation.

PMID- 14573904
TI  - Assay system for the effect of prostaglandin E(2) in the determination of
      polarized cytokine production.

PMID- 14573905
TI  - Chemotaxis and interaction with vascular or lymphatic endothelium.

PMID- 14573906
TI  - Analysis of integrin-dependent rapid adhesion under laminar-flow conditions.

PMID- 14573907
TI  - Posttranslational processing of chemokines.

PMID- 14573908
TI  - Chemotactic profiling of lymphocyte subpopulations.

PMID- 14573910
TI  - Evaluation of Rho family small G-protein activity induced by integrin ligation on
      human leukocytes.

PMID- 14573909
TI  - Measurement of the levels of polymerized actin (F-actin) in chemokine-stimulated
      lymphocytes and GFP-coupled cDNA transfected lymphoid cells by flow cytometry.

PMID- 14573911
TI  - Reconstructing leukocyte migration in 3D extracellular matrix by time-lapse
      videomicroscopy and computer-assisted tracking.

PMID- 14573912
TI  - Analyzing chemotaxis using Dictyostelium discoideum as a model system.

PMID- 14573913
TI  - Conditional transgenic models to study chemokine biology.

PMID- 14573914
TI  - Intravital microscopy as a tool for studying recruitment and chemotaxis.

PMID- 14573915
TI  - Tracking antigen-specific lymphocytes in vivo.

PMID- 14573916
TI  - Analysis of homing-receptor expression on infiltrating leukocytes in disease
      states.

PMID- 14573917
TI  - Interaction of viral chemokine inhibitors with chemokines.

PMID- 14573918
TI  - Discovery of small-molecule antagonists of chemokine receptors: screening
      strategy and assays.

PMID- 14573919
TI  - Visualization and analysis of adhesive events in brain microvessels by using
      intravital microscopy.

PMID- 14573920
TI  - Animal models to study chemokine receptor function: in vivo mouse models of
      allergic airway inflammation.

PMID- 14573921
TI  - Assessing the role of multiple phosphoinositide 3-kinases in chemokine signaling:
      use of dominant negative mutants controlled by a tetracycline-regulated gene
      expression system.

PMID- 14573922
TI  - In vitro and in vivo models to study chemokine regulation of angiogenesis.

PMID- 14573923
TI  - Real-time in vitro assay for studying chemoattractant-triggered leukocyte
      transendothelial migration under physiological flow conditions.

PMID- 14573924
TI  - Generation of monoclonal antibodies against chemokine receptors.

PMID- 14573925
TI  - Detection of high-affinity alpha4-integrin upon leukocyte stimulation by
      chemoattractants or chemokines.

PMID- 14573926
TI  - Molecular diagnosis of Fanconi anemia and dyskeratosis congenita.

PMID- 14573927
TI  - Molecular diagnosis of Diamond-Blackfan anemia.

PMID- 14573928
TI  - Antenatal diagnosis of hemoglobinopathies.

PMID- 14573929
TI  - Prenatal diagnosis of hemophilia.

PMID- 14573930
TI  - Human platelet antigen genotyping by PCR-SSP in neonatal/fetal alloimmune
      thrombocytopenia.

PMID- 14573931
TI  - Multiplex PCR for the detection of the factor V Leiden and prothrombin 20210A
      mutations.

PMID- 14573932
TI  - Molecular diagnosis of congenital immunodeficiency.

PMID- 14573933
TI  - Molecular techniques to improve outcome in childhood ALL.

PMID- 14573934
TI  - Molecular cytogenetics in childhood leukemia.

PMID- 14573935
TI  - Fluorescent IgH fingerprinting to assess minimal residual disease in childhood B
      lineage ALL.

PMID- 14573936
TI  - Real-time quantitative RT-PCR to detect fusion gene transcripts associated with
      AML.

PMID- 14573937
TI  - Real-time PCR to detect minimal residual disease in childhood ALL.

PMID- 14573938
TI  - Oligonucleotide microarray analysis of gene expression in leukemia.

PMID- 14573939
TI  - HLA low-resolution genotyping for hematopoietic stem cell transplantation.

PMID- 14573940
TI  - DNA sequencing as a tissue-typing tool.

PMID- 14573941
TI  - Analysis of chimerism after stem cell transplantation.

PMID- 14573942
TI  - The phase problem.
AB  - Given recent advances in phasing methods, those new to protein crystallography
      may be forgiven for asking 'what problem?'. As many of those attending the CCP4
      meeting come from a biological background, struggling with expression and
      crystallization, this introductory paper aims to introduce some of the basics
      that will hopefully make the subsequent papers penetrable. What is the 'phase' in
      crystallography? What is 'the problem'? How can we overcome the problem? The
      paper will emphasize that the phase values can only be discovered through some
      prior knowledge of the structure. The paper will canter through direct methods,
      isomorphous replacement, anomalous scattering and molecular replacement. As
      phasing is the most acronymic realm of crystallography, MR, SIR, SIRAS, MIR,
      MIRAS, MAD and SAD will be expanded and explained in part. Along the way, we will
      meet some of the heroes of protein crystallography such as Perutz, Kendrew,
      Crick, Rossmann and Blow who established many of the phasing methods in the UK.
      It is inevitable that some basic mathematics is encountered, but this will be
      done as gently as possible.

PMID- 14573943
TI  - New ways of looking at experimental phasing.
AB  - In the original work by Blow and Crick, experimental phasing was formulated as a
      least-squares problem. For good data on good derivatives this approach works
      reasonably well, but we now attempt to extract more information from poorer data
      than in the past. As in many other crystallographic problems, the assumptions
      underlying the use of least squares for phasing are not satisfied, particularly
      for poor derivatives. The introduction of maximum likelihood (and more powerful
      computers) has led to substantial improvements. For computational convenience,
      these new methods still make many assumptions about the independence of different
      measurements and sources of error. A more general formulation for the probability
      distributions underlying likelihood-based methods for both experimental phasing
      and molecular-replacement phasing is reviewed. In the new formulation, all the
      structure factors associated with a particular hkl are considered to be related
      by a complex multivariate normal distribution. When it is assumed that certain
      errors are independent, the general formulation reduces to current likelihood
      targets. However, the new formulation makes the necessary assumptions more
      explicit and points the way to improving phasing using both isomorphous and
      anomalous differences.

PMID- 14573944
TI  - Heavy-atom derivatization.
AB  - Most of the standard methods of solving macromolecular structures involve
      producing a protein crystal that is derivatized by an anomalous scatterer or
      heavy atom (MIR, SIRAS, MAD, SAD etc.). The theoretical methodology which
      underpins the extraction of phase information from such derivatives is widely
      available in the literature. In addition, there are comprehensive sources of
      information on the chemistry of heavy-atom compounds and the ligands with which
      they are known to interact, as well as the Heavy Atom Databank accessible on the
      World Wide Web. This contribution therefore aims to provide some information on
      the less well documented practical problems of firstly deciding on an overall
      strategy for derivatization and secondly performing the physical manipulations
      involved in producing heavy-atom derivatives from native protein crystals and
      then cryocooling them. Ways to optimize the chances of isomorphous unit cells are
      suggested. Methods of determining whether or not the heavy atom is bound are
      outlined, including the powerful technique of PIXE (particle-induced X-ray
      emission).

PMID- 14573945
TI  - A new class of lanthanide complexes to obtain high-phasing-power heavy-atom
      derivatives for macromolecular crystallography.
AB  - Because of their intense white lines and large f" values, lanthanide atoms are of
      great interest for solving structures of biological macromolecules using single
      wavelength anomalous diffraction (SAD) or multiple-wavelength anomalous
      diffraction (MAD) methods. In this work, a series of seven gadolinium complexes
      are described which provide excellent derivatives for anomalous diffraction
      experiments in biological systems. These highly soluble lanthanide complexes can
      easily be introduced into protein crystals either by soaking or by co
      crystallization, without significantly affecting the crystallization conditions,
      by employing highly concentrated complex solutions ( approximately 100 mM). De
      novo phasing by the SAD method was carried out with several proteins of known as
      well as previously unknown structures by employing this new class of heavy-atom
      compounds. Diffraction data were collected either with a laboratory source,
      making use of the high anomalous signal (f" = 12 e(-)) of gadolinium with Cu
      Kalpha radiation, or with synchrotron radiation at the peak of the gadolinium
      L(III) absorption edge, which exhibits a strong white line (lambda = 1.711 A, f"
      = 28 e(-)). Using one of these gadolinium complexes, Gd-HPDO3A, the structure of
      a bacterial chimeric ornithine carbamoyl transferase, OTCase3630, a dodecameric
      protein of 450 kDa, was determined. Employed with the SAD method, these seven
      complexes could be of particular interest for high-throughput macromolecular
      crystallography.

PMID- 14573946
TI  - Triiodide derivatization in protein crystallography.
AB  - Methods for producing protein derivatives using cryosoak techniques with
      triiodide solutions are described. The methods have been tested using six
      different proteins. SAD/SIRAS phasing was attempted for each protein using data
      measured with conventional Cu Kalpha X-ray equipment and synchrotron radiation.
      Refinement of all six derivative structures showed that iodine is able to bind as
      I(-) (as observed with standard halide soaks) and also as the polyiodide anions
      I(3)(-) and I(5)(-). The various species are able to bind through hydrogen-bond
      interactions and to more hydrophobic regions of the protein at surface pockets
      and in intermolecular and intramolecular cavities. On the whole, the derivative
      agent behaves promiscuously in terms of its binding to proteins and is capable of
      generating sufficient phasing power from in-house Cu Kalpha data to permit
      structure solution by SAD. The results of the phasing experiments and structure
      refinements are presented.

PMID- 14573947
TI  - Selling candles in a post-Edison world: phasing with noble gases bound within
      engineered sites.
AB  - The utility of noble gases for phase determination has been limited by the lack
      of naturally occurring binding sites in proteins. Wild-type T4 lysozyme contains
      one such binding site. By mutating large hydrophobic residues to alanine,
      additional noble-gas binding sites have been successfully introduced into this
      protein. Using data from xenon derivatives of the wild type, two single mutants
      and the corresponding double mutant, experimental phases for T4 lysozyme have
      been determined using standard multiple isomorphous replacement (MIR) techniques.
      These phases, which were obtained from room-temperature data collected on a
      rotating-anode source, are comparable in quality with phases calculated using
      selenomethionine-based multiwavelength anomalous dispersion (MAD) methods on
      frozen crystals at a synchrotron. In addition, this method of introducing noble
      gas binding sites near specific residues should provide useful information for
      determining the register of amino acids within electron-density maps and the
      positions of molecules within the unit cell.

PMID- 14573948
TI  - Optimizing data collection for structure determination.
AB  - The ultimate purpose of diffraction data collection is to produce a data set
      which will result in the required structural information about the molecule of
      interest. This usually entails collecting a complete and accurate set of
      reflection intensities to as high a resolution as possible. In practice, the
      characteristics of the crystal and properties of the X-ray source can be limiting
      factors to the data-set quality that can be achieved and a careful strategy has
      to be used to extract the maximum amount of information from the data within the
      experimental constraints. In the particular case of data intended for phasing
      using anomalous dispersion, the synchrotron beamline properties are relevant to
      determine how many wavelengths (one or more) should be used for the experiment
      and what the wavelength values should be. This will in turn affect the detailed
      strategy for data collection, including decisions about the data-collection
      sequence and how much data to collect at each wavelength. Collection of
      multiwavelength anomalous dispersion (MAD) data at three different wavelengths
      can provide very accurate experimental phases. Two-wavelength MAD experiments may
      offer the best compromise between phase quality and minimizing the effects of
      radiation damage to the sample. However, MAD experiments are demanding in terms
      of beamline wavelength range, easy tunability, stability and reproducibility.
      When the beamline cannot fulfill these demands, single-wavelength experiments may
      be a better option.

PMID- 14573949
TI  - Away from the edge: SAD phasing from the sulfur anomalous signal measured in
      house with chromium radiation.
AB  - Anomalous scattering with soft X-ray radiation opens new possibilities in phasing
      for macromolecular crystallography. Anomalous scattering from S atoms collected
      on an in-house chromium radiation source (lambda = 2.29 A) was used to phase the
      X-ray diffraction data of thaumatin (22 kDa) and trypsin (24 kDa) crystals. The
      contribution to the anomalous term, Deltaf" = 1.14 e(-), from sulfur for Cr
      Kalpha radiation is doubled compared with that for Cu Kalpha radiation, Deltaf" =
      0.56 e(-). The direct-methods programs RANTAN or SHELXD successfully found sulfur
      positions using data sets with resolution limited to 3.5 A. The statistical
      phasing program SHARP was used to produce the electron-density maps using the
      sulfur anomalous signal alone at low resolution ( approximately 3.5 A). An
      interpretable electron-density map for each structure was obtained solely from
      the phases derived from single-wavelength anomalous dispersion (SAD) data
      obtained using Cr Kalpha radiation. Much fewer data (that is, lower redundancy)
      are required for this sulfur SAD phasing procedure compared with the highly
      redundant data reported in the sulfur SAD phasing procedure with Cu Kalpha
      radiation. Cr Kalpha radiation can also improve the strength of anomalous
      scattering of many other intrinsic elements in macromolecules, such as calcium,
      zinc and phosphorus, because of the increased Deltaf". Furthermore, the anomalous
      scattering of selenium is increased substantially from 1.14 e(-) with Cu Kalpha
      radiation to 2.28 e(-) with Cr Kalpha radiation. In order to measure the small
      Bijvoet differences accurately, several devices were developed for the
      experiment, including an Osmic Confocal MaxFlux optic optimized for Cr Kalpha
      radiation, a helium path and a beam stop. In the cases studied here, radiation
      damage to the samples and reduction of anomalous signal were observed in some
      long exposure time data sets. Therefore, an adequate data-collection strategy to
      maximize the completeness in a short scan range was used in subsequent data
      collections. The results show that the anomalous signal of S atoms can be
      collected quickly. Since the absorption of solvent and the loop may no longer be
      negligible with Cr Kalpha radiation, the orientation of the crystal and exposure
      time were taken into account in order to minimize the effects of radiation damage
      and absorption. This experimental study shows that using Cr Kalpha radiation from
      an in-house rotating-anode X-ray generator can provide sufficient phasing power
      from sulfur anomalous signals to routinely phase protein diffraction data.

PMID- 14573950
TI  - Is it jolly SAD?
AB  - Examples of phasing macromolecular crystal structures based on single-wavelength
      anomalous dispersion (SAD) have demonstrated that this approach may have general
      applications in structural biology. With better data-collection facilities and
      cryogenic techniques, combined with powerful data-processing, phasing and density
      modification programs, the SAD approach may prove simpler than phasing from multi
      wavelength (MAD) measurements. It can be performed at any wavelength where
      anomalous scattering can be observed, in many cases using laboratory X-ray
      sources. However, there is still a need for accurate data, successful phase
      improvement and a certain amount of luck. This paper extends the discussion of
      Jolly SAD in Dauter et al. [Dauter, Z., Dauter, M. & Dodson, E. (2002), Acta
      Cryst. D58, 494-506].

PMID- 14573951
TI  - Substructure search procedures for macromolecular structures.
AB  - This paper accompanies a lecture given at the 2003 CCP4 Study Weekend on
      experimental phasing. The first part is an overview of the fundamentals of
      Patterson methods and direct methods with the audience of the CCP4 Study Weekend
      in mind. In the second part, a new hybrid substructure search is outlined.

PMID- 14573952
TI  - On symmetries of substructures.
AB  - This paper accompanies a lecture given at the 2003 CCP4 Study Weekend on
      experimental phasing. With the audience of the CCP4 Study Weekend in mind, an
      overview is given of symmetries of substructures and the implications for single
      isomorphous replacement and single anomalous diffraction phasing procedures, as
      well as difference Fourier analyses. Pointers are also provided to practical
      tools for working with substructure symmetries.

PMID- 14573953
TI  - 'MAD'ly phasing the extracellular domain of the LDL receptor: a medium-sized
      protein, large tungsten clusters and multiple non-isomorphous crystals.
AB  - The crystal structure of the extracellular domain of the LDL receptor (LDL-R) was
      determined in a MAD experiment using 12-tungstophosphate clusters as anomalous
      scatterers. While useful for phasing, the tungsten clusters rendered the crystals
      radiation-sensitive and non-isomorphous and profoundly altered the diffraction
      data, causing complications. The work is presented as a case study for phasing a
      medium-sized protein (700 residues) at low resolution (4 A) with multiple non
      isomorphous crystals containing 31 W atoms in the asymmetric unit.

PMID- 14573954
TI  - Optimization of selenium substructures as obtained from SHELXD.
AB  - Using the signal of naturally inbuilt or artificially introduced anomalous
      scatterers to derive initial phases in a macromolecular crystal structure
      determination has become routine in recent years. In the context of high
      throughput crystallography in particular, MAD and SAD (multiple- and single
      wavelength anomalous dispersion) methods are central tools. For both techniques,
      a crucial step is the determination of the substructure of anomalous scatterers;
      subsequent phasing procedures will profit from a substructure model that is as
      accurate as possible. The choice of the subset of the diffraction data to be used
      for the substructure determination has a strong influence on the quality of the
      substructure and can make the difference between success and failure. The
      accuracy of selenium substructures obtained using F(A) values or various
      anomalous differences truncated to different resolutions has been investigated by
      comparing the sites determined by SHELXD with the selenium positions in the
      refined models. Based on the analysis, some recommendations for obtaining
      accurate and precise substructures are derived.

PMID- 14573955
TI  - Introduction to twinning.
AB  - A twinned crystal is an aggregate in which different domains are joined together
      according to a specific symmetry operation: the twin law. The diffraction
      patterns derived from different domains are rotated, reflected or inverted with
      respect to each other, depending on the nature of the relationship between the
      different domains, and weighted according to the quantity of a particular domain
      present in the crystal. The diffraction pattern measured during data collection
      is a superposition of all of these. Reflections from different domains may
      overlap and twinned crystals fall broadly into two categories in which either all
      reflections or only certain zones of reflections are affected by overlap. The
      former occurs when a crystal lattice belongs to a higher point group than the
      crystal structure itself; the latter frequently occurs when the twin law is a
      symmetry operation belonging to a higher symmetry supercell.

PMID- 14573956
TI  - Twinned crystals and anomalous phasing.
AB  - Merohedral or pseudomerohedral twinning of crystals cannot be identified from
      inspection of the diffraction patterns. Several methods for the identification of
      twinning and the estimation of the twin fraction are suitable for macromolecular
      crystals and all are based on the statistical properties of the measured
      diffraction intensities. If the crystal twin fraction is estimated and is not too
      close to 0.5, the diffraction data can be detwinned; that is, related to the
      individual crystal specimen. However, the detwinning procedure invariably
      introduces additional inaccuracies to the estimated intensities, which
      substantially increase when the twin fraction approaches 0.5. In some cases, a
      crystal structure can be solved with the original twinned data by standard
      techniques such as molecular replacement, multiple isomorphous replacement or
      multiwavelength anomalous diffraction. Test calculations on data collected from a
      twinned crystal of gpD, the bacteriophage lambda capsid protein, show that the
      single-wavelength anomalous diffraction (SAD) method can be used to solve its
      structure even if the data set corresponds to a perfectly twinned crystal with a
      twin fraction of 0.5.

PMID- 14573957
TI  - MIR phasing using merohedrally twinned crystals.
AB  - Merohedral twinning is a crystal-growth disorder that seriously hinders the
      determination of macromolecular crystal structures by isomorphous replacement.
      The strategies used in the structures solved so far are discussed. Several
      methods can be used to determine the extent of twinning, the twin fraction and to
      detwin the data. Accurate determination of the twin fraction by analysing heavy
      atom refinement statistics is possible, but only influences the resulting phases
      slightly. It seems more crucial to restrict the variation in twin fractions
      between data sets, either by making the twin fractions of some data sets
      artificially higher or by screening crystals to obtain data with a low twin
      fraction.

PMID- 14573958
TI  - Generation, representation and flow of phase information in structure
      determination: recent developments in and around SHARP 2.0.
AB  - The methods for treating experimental data in the isomorphous replacement and
      anomalous scattering methods of macromolecular phase determination have undergone
      considerable evolution since their inception 50 years ago. The successive
      formulations used are reviewed, from the most simplistic viewpoint to the most
      advanced, including the exploration of some blind alleys. A new treatment is
      proposed and demonstrated for the improved encoding and subsequent exploitation
      of phase information in the complex plane. It is concluded that there is still
      considerable scope for further improvements in the statistical analysis of phase
      information, which touch upon numerous fundamental issues related to data
      processing and experimental design.

PMID- 14573959
TI  - Measurement errors and their consequences in protein crystallography.
AB  - This article analyzes the relative impact of various types of measurement
      uncertainties on different stages of structure determination. The treatment of
      errors is an important part of the experimental process and becomes critical when
      data quality is barely sufficient to solve and/or answer detailed questions about
      the structure. The sources and types of experimental errors are described and
      methods of minimizing their impact are discussed. Practical calculations of sigma
      estimates in DENZO and SCALEPACK are presented.

PMID- 14573960
TI  - Phasing the AP2 core complex with Xe, Hg and Se.
AB  - The 200 kDa core of the heterotetrameric AP2 clathrin adaptor complex was phased
      with xenon, mercury and selenomethionine derivatives. The phasing has been
      analysed in retrospect to determine how many of the derivative data sets were
      necessary for optimum phasing and what features were most useful in deciding
      which derivatives would make a positive contribution. The relative contributions
      of the different derivatives indicate that the most important phasing came from
      the two Xe data sets collected at long wavelengths (1.74 and 1.98 A) to enhance
      the anomalous signal. The mercury derivatives were less powerful but made a
      useful contribution, although inclusion of a poor second wavelength set was
      detrimental, probably because of radiation damage. The SeMet data were less
      useful for phasing because of incomplete incorporation of selenium owing to the
      expression conditions needed, but they were useful in chain-tracing.

PMID- 14573961
TI  - Phasing the 30S ribosomal subunit structure.
AB  - The methods involved in determining the 850 kDa structure of the 30S ribosomal
      subunit from Thermus thermophilus were in many ways identical to those that are
      generally used in standard protein crystallography. This paper reviews and
      analyses the methods that can be used in phasing such large structures and shows
      that the anomalous signal collected from heavy-atom compounds bound to the RNA is
      both necessary and sufficient for ab initio structure determination at high
      resolution. In addition, measures to counter problems with non-isomorphism and
      radiation decay are described.

PMID- 14573962
TI  - Comparison of temperament and character profiles of anesthesiologists and
      surgeons: a preliminary study.
AB  - BACKGROUND: Given the high levels of stress in anesthesiologists and also their
      close working liaison with surgeons, it may be worthwhile to compare the
      personality profiles of these two groups of professionals. AIM: To compare the
      personality profiles of surgeons and anesthesiologists, using a well-standardized
      and validated instrument. SETTINGS AND DESIGN: Survey (cross-sectional) on
      surgeons and anesthesiologists working in several medical institutes in India.
      MATERIAL & METHODS: The self-report Temperament and Character Inventory, 125-item
      version (TCI-125) was mailed out to an incidental sample of surgeons and
      anesthesiologists working in medical institutes in India. Of the 200
      questionnaires sent (100 to anesthesiologists and surgeons each), 93 completed
      responses were returned (46 anesthesiologists, 47 surgeons; return rate 46.5%).
      STATISTICAL ANALYSIS: Student's unpaired 't' test; P<0.05 was considered
      statistically significant. RESULTS: The mean scores of anesthesiologists vis-a
      vis surgeons on the various temperament dimensions were Novelty seeking: 8.6 vs.
      9.2; Harm avoidance: 7.3 vs. 8.1; Reward dependence: 8.1 vs. 8.0; and
      Persistence: 3.0 vs. 3.1, respectively. Similar scores for the character
      dimensions were Self-directedness: 16.9 vs. 15.9; Cooperativeness: 17.5 vs. 16.5;
      and Self-transcendence: 7.0 vs. 6.7, respectively. There was no significant
      difference between the surgeons and anesthesiologists on any of the temperament
      and character variables of personality chosen for the study. CONCLUSION:
      Personality measures did not differ significantly between surgeons and
      anesthesiologists in this preliminary investigation. If replicated on a larger
      and more representative sample, the findings have clinical relevance to improve
      the working relationship between these two groups of closely working
      professionals.

PMID- 14573963
TI  - Dermatoglyphics in rheumatoid arthritis.
AB  - Patients with rheumatoid arthritis have been referred to Division of Human
      Genetics for counselling. Qualitative dermatoglyphics comprising of finger print
      pattern, interdigital pattern, hypothenar pattern and palmar crease were studied
      on 26 female and 11 male rheumatoid arthritis patients. Comparison between
      patient male and control male; and patient female and control female has been
      done. 'Chi' square test was performed. In male patients, with hands together,
      arches were increased, loops/ whorls were decreased. Partial Simian crease was
      significantly increased. In the right hand, patterns were increased in the 3rd
      interdigital area. On the other hand, in female patients there was a significant
      increase in whorls and decrease in loops on the first finger on both the hands,
      increase in arches on the 3rd finger; both arches and whorls on the 4th finger of
      left hand. Present study has emphasized that dermatoglyphics could be applied as
      a diagnostic tool to patients with rheumatoid arthritis.

PMID- 14573964
TI  - Coronary artery disease incidence between type II diabetic and non-diabetic
      patients with Leriche syndrome.
AB  - BACKGROUND: Coronary artery disease (CAD) is the major determinant of
      preoperative morbidity and mortality for patients requiring major vascular
      surgery. The management of CAD in these patients is controversial. AIMS: The
      incidence and severity of CAD in diabetic and non-diabetic patients with Leriche
      syndrome was explored. SETTINGS AND DESIGN: 107 patients with Leriche syndrome
      were selected as major vascular occlusion and grouped according to their diabetic
      Status. Sex, age, dyslipidemia, obesity, hypertension, clinic cardiac status,
      coronary angiographic lesions and coronary revascularisation procedures were
      noted. MATERIAL & METHODS: Patients' demographics, intra-operative and per
      operative data were recorded and compared. In every patient with Leriche syndrome
      scheduled for elective vascular reconstruction coronary angiography was
      performed. Lesions were evaluated for the percentages of stenosis. Preliminary
      coronary bypass or percutaneous coronary intervention was recommended for those
      found to have advanced or severe CAD. Results of revascularisation procedures
      were compared. STATISTICAL ANALYSIS USED: Chi-square or Fisher exact chi-square
      test is used for conditional variables. Independent samples was analysed by using
      t-test. Kruskal-Wallis variance test was used if the variances are not
      homogeneous according to the Levene test. RESULTS: No difference was found in
      both groups except family history and obesity. Coronary angiographic
      investigation indicates that 59% of DIAB group and 38% of NONDIAB group patients
      have advanced or severe CAD which has a high probability for myocardial
      revascularization. Overall revascularisation rate is 37.8% in DIAB group and
      45.7% in NONDIAB group (p=0,641). Preoperative mortality was found 2.7% in
      diabetics and 4.2% in non-diabetics (p=0.342). CONCLUSIONS: Leriche syndrome with
      diabetes mellitus is more likely to have advanced coronary disease than those
      without diabetes mellitus. Coronary angiography and subsequent revascularisation
      should be performed only in those patients who require major vascular surgery.

PMID- 14573965
TI  - Socioeconomic burden of nosocomial infections.
AB  - Nosocomial infection represents an important public health problem in developing
      countries as in developed ones. Economic concerns have taken on increasing
      importance in infection control since the mid 1970s in the USA, however there are
      few papers on the economics of NI in other countries. Studies on the costs of NI
      have used different methods, definitions and degrees of stringency when
      calculating indirect costs and there is therefore still uncertainty over their
      true economic impact on the community and on the workplace economy. Drug and
      especially antibiotic acquisition in addition to increased length of stay are the
      widely and well described parameters. Extra cost of NI include; bed, intensive
      care unit stay, hematological, biochemical, microbiological and radiological
      tests, antibiotics, other drugs, extra surgical procedures and working hours. In
      addition to high morbidity and mortality one of the well described parameters is
      the extra length of stay in the hospital. High mortality rates and economic
      expense which NI represents emphasizes the justification for measures of control
      of this entity. To estimate better the current personnel and financial resources
      necessary to support infection control activities and to prevent NI, it is
      imperative that those conducting studies of hospital epidemiology and healthcare
      outcomes research determine these current costs.

PMID- 14573966
TI  - Smoking behavior and initiation of smoking among adolescent - a threat to public
      health.

PMID- 14573967
TI  - Does the right of a doctor to prescribe a branded drug without informed consent
      of the patient constitute a violation of patient's rights?

PMID- 14573968
TI  - Viral hepatitis (Part - III).

PMID- 14573969
TI  - Visual evoked potentials in konzo, a spastic paraparesis of acute onset in
      Africa.
AB  - AIM: To assess whether or not visual evoked potentials (VEPs) are abnormal in
      konzo, a para/tetraparesis of sudden onset, and to correlate the findings to the
      clinical picture of the disorder. METHODS: VEPs were recorded in 23 patients (9
      men and 14 women, mean age: 23 +/- 10 years) suffering from konzo, and 38 healthy
      subjects (20 men and 18 women, mean age: 27 +/- 15 years). The mean P100
      latencies and peak-to-peak N75-P100 amplitudes of each eye were measured and
      compared in the two groups. The mean interocular P100 latency and amplitude
      differences were calculated and also compared. RESULTS: VEPs were abnormal in
      11/23 patients (48%) consisting of P100 prolongation (7 subjects), absence of
      P100 wave (2 subjects) or an atypical waveform (2 subjects). The mean P100
      latency value of the konzo group was significantly increased as compared with the
      mean (+ 2.5 SD) of the reference values from healthy subjects (p < 0.05). There
      was a statistically significant decrease of amplitude in konzo patients compared
      to normal subjects (p < 0.05) with, however, only 2 patients outside the 95%
      confidence limits. Six patients (27%) had abnormal VEPs despite normal visual
      acuity. These abnormalities were symmetric and a relation could be found between
      neither the duration nor the severity of the disease and the VEP perturbation.
      CONCLUSION: The main features of these abnormalities are delayed P100 latency and
      decreased amplitude. These findings indicate involvement of visual pathways and
      seem to suggest the presence of axonal loss in the prechiasmal visual pathways in
      konzo. This study provides evidence that the neurodamage in konzo extends to the
      visual pathways.

PMID- 14573970
TI  - Primary vitrectomy in complicated rhegmatogenous retinal detachment--a survey of
      205 eyes.
AB  - INTRODUCTION: In a few types of rhegmatogenous retinal detachment (RRD), scleral
      buckling (SB) has a lower success, and, here, pars plana vitrectomy (PPV) is a
      good alternative option. This survey reviews the indications and the surgical
      outcome of primary PPV with internal tamponade. PATIENTS AND METHODS: We reviewed
      205 eyes operated by primary PPV for RRD at the Department of Ophthalmology of
      the Philipps University Marburg between the years 1990 and 1997. The indications
      of PPV were: holes greater than 90 degrees; holes posterior to the equator;
      proliferative vitreoretinopathy grade C; pseudophakic status. RESULTS: A complete
      reattachment of the retina after absorption of the gas or after silicone oil
      removal was achieved by 1 operation in 146 eyes (71.2%) and in 195 eyes (95.2%)
      by a second intervention. CONCLUSION: Although SB is the standard procedure for
      the treatment of RRD, complicated cases can be treated successfully with primary
      PPV.

PMID- 14573971
TI  - Long-term results of transscleral cyclophotocoagulation in refractory pediatric
      glaucoma patients.
AB  - We evaluated efficacy and complications of diode laser cyclophotocoagulation in
      pediatric patients with refractory glaucomas. The retrospective study comprised
      69 eyes of 53 pediatric patients with uncontrolled refractory glaucoma treated by
      transscleral diode laser cyclophotocoagulation. The mean age was 6.1 +/- 4.29
      (range 0.9-15) years. The main parameters evaluated were: intraocular pressure
      (IOP), visual acuity, and complications. The mean follow-up period was 5.6 +/-
      2.8 (range 2.2-9.5) years. Treatment success was defined as a postoperative IOP
      of </=21 mm Hg, with or without adjunctive glaucoma medications. The baseline
      mean pretreatment IOP was 34.08 +/- 7.13 (range 24-47) mm Hg. The final mean
      postoperative IOP was 20.81 +/- 6.38 (range 12-33) mm Hg after a mean of 2.13 +/-
      1.47 (range 1-6) laser procedures. After one treatment session, 66% of the eyes
      had a successful reduction in IOP (</=21 mm Hg), but this had fallen to 41% by 1
      year. With repeat cyclophotocoagulation, 79% of the eyes had a clinically
      effective reduction in IOP(</=21 mm Hg) for 1 year (mean 7.1-month interval
      between treatments). Postoperative complications included choroidal detachment in
      4 eyes and retinal detachment in 2 eyes with progression of vision loss. All
      these complications occurred in aphakic patients. Cyclophotocoagulation by diode
      laser is a useful therapy for the treatment of refractory pediatric glaucomas
      with uncontrolled IOP. Cyclodiode repeated treatment can provide effective
      control of IOP with a low risk of severe complications. Aphakic patients may have
      an increased risk of postoperative complications.

PMID- 14573972
TI  - Is membrane extraction in cases of exudative age-related macular degeneration
      still up-to-date? A 4-year resume.
AB  - BACKGROUND: Age-related macular degeneration (AMD) is a frequent cause of an
      irreversible loss of the ability to read. The non-exudative form of AMD has not
      been therapeutically approached in the past in contrast to the exudative form
      with choroidal neovascularizations (CNVs). Parafoveal laser coagulation can be
      applied, and in cases of subfoveal location a pars plana vitrectomy with
      subretinal resection of the CNV is possible. MATERIAL AND METHODS: Since 1995, we
      have operated 46 eyes of 45 patients with CNV developing from AMD. Patient ages
      ranged from 63 to 85 years (mean 71.8 years). Pre- and postoperatively we
      performed vision tests, fluorescence angiographies with sodium fluorescein and
      indocyanine green. Follow-up times ranged from 3 to 28 months (mean 12.3 months).
      RESULTS: Pre-operative vision was 0.10 (range: hand movements to 0.4).
      Postoperative vision at the end of the follow-up period was 0.12 (range: hand
      movements to 0.4). Vision at the end of the follow-up was lower in 41%, unchanged
      in 20% and improved in 39%. In 43 eyes, a non-exudative form of AMD developed.
      Two eyes had a recurrent CNV, which was removed successfully with a second pars
      plana vitrectomy. Three patients developed a retinal detachment, which was
      successfully treated by pars plana vitrectomy, encircling buckle and gas
      tamponade. CONCLUSIONS: We still have to wait for the results of the photodynamic
      study trials and a randomized study of macular dislocation. Subretinal removal of
      the CNV by pars plana vitrectomy allows a stabilization of the visual function in
      most of our cases of AMD. This method inhibits the development of large
      pseudotumour-like scars. Postoperatively remaining pigment epithelial defects
      with choroidal atrophies however limit a visual rehabilitation so that reading
      vision can only be achieved in cases with good pre-operative vision. Long-term
      results of photodynamic therapy are still lacking and have to show its
      effectiveness over greater time spans.

PMID- 14573973
TI  - Incidence of cystoid macular edema after uncomplicated phacoemulsification.
AB  - We determined the incidence and causes of clinical and angiographic cystoid
      macular edema (CME) after uncomplicated phacoemulsification and intraocular lens
      implantation in otherwise normal eyes. This study comprised 252 eyes of 252
      patients who had uncomplicated phacoemulsification with continuous curvilinear
      capsulorhexis and in-the-bag acrylic intraocular lens implantation. The presence
      of clinical and angiographic CME was evaluated 45 days after surgery, using
      fundus fluorescein angiography. Age, sex, cataract type, iris color, and real
      phacoemulsification time of the patients were also recorded. The mean age of the
      patients was 69.86 (range 60-82) years). Clinical CME was not detected in any eye
      at any postoperative visit. There were 23 cases with angiographic CME (9.1%).
      There were no significant differences between the groups who were later found to
      be angiographically CME-positive or CME-negative in any variable recorded (p
      >0.05). The incidences of clinical and angiographic CME after uncomplicated
      phacoemulsification were 0 and 9.1%, respectively. These results indicate that
      the occurrence of clinical CME has greatly reduced after uncomplicated
      phacoemulsification operations, but the incidence of angiographic CME is still
      nearly equal to the incidence of the extracapsular technique.

PMID- 14573974
TI  - Subjective visual experience and pain level during phacoemulsification and
      intraocular lens implantation under topical anesthesia.
AB  - PURPOSE: To investigate the subjective visual experiences and pain during the
      phacoemulsification and intraocular lens (IOL) implantation under topical
      anesthesia, and whether these parameters change according to the stage of
      phacoemulsification cataract surgery. METHODS: Forty eyes of 40 patients with
      cataract undergoing phacoemulsification and IOL implantation under topical
      anesthesia were included in this study. The patients were told that they would be
      asked about their visual experiences and pain level, if any, during every stage
      of the surgery. As for degree of the pain, a 5-grade scale was used. The surgery
      was divided into 9 stages, i.e., clear corneal incision, continuous curvilinear
      capsulorhexis, side-port incisions at 3 and 9 o'clock positions, hydrodissection,
      nuclear rotation, phacoemulsification, bimanual irrigation and aspiration, IOL
      implantation, apposition of corneal incisions with stromal hydration. RESULTS:
      All subjects (100%) reported that they had seen some kind of light during the
      operation. Thirty-eight patients (95%) said that they had seen one or more
      colors. In 32 patients (80%), the light intensity decreased, and colors blurred
      significantly following the hydrodissection. As for the pain level during
      surgery, the overall pain score was found to be 0.40. The highest mean pain score
      was noted during IOL implantation stage followed by phacoemulsification and
      bimanual irrigation-aspiration. CONCLUSION: Topical anesthesia is both a safe and
      effective method for small-incision clear corneal phacoemulsification cataract
      surgery. Patients may experience visual sensations, and the pain felt during the
      operation is low and tolerable. Visual experiences and pain level may change
      according to the stage of phacoemulsification cataract surgery.

PMID- 14573975
TI  - Visual outcome in macular retinoblastoma treated with primary chemotherapy.
AB  - In this prospective clinical study, we treated 8 patients (8 eyes, 11 tumors) of
      macular retinoblastoma with chemotherapy alone, with the aim of avoiding visual
      loss because of retinal damage by radiation or adjuvant therapy and to assess
      their final visual outcome. The mean basal dimension of the tumor was 5.0 +/- 2.6
      mm and the mean height was 2.9 +/- 1.3 mm. The fovea was involved in 4 patients
      (50%) and foveal detachment was present in 3 patients (37.5%). All the patients
      required less than 6 cycles for tumor control. Four patients (50%) obtained
      visual acuities ranging from 20/25 to 20/200. Two patients (25%) could gain
      visual acuity of 20/20. The mean follow-up of patients was 3.24 +/- 0.9 years
      (range 2-5). No patient developed recurrence or metastatic disease. In
      conclusion, recent trends for ocular salvage have favored chemoreduction followed
      by focal therapy for the treatment of retinoblastoma. This study supports the
      consideration of chemotherapy alone as the primary treatment in eyes with macular
      retinoblastomas, under close supervision, with satisfactory visual outcome.

PMID- 14573976
TI  - Tenascin-C levels in the vitreous of patients with proliferative
      vitreoretinopathy.
AB  - PURPOSE: To determine whether tenascin-C levels are elevated in the vitreous of
      patients with proliferative vitreoretinopathy (PVR). METHODS: We assayed tenascin
      C levels in vitreous samples of 110 consecutive patients with PVR (30 eyes),
      rhegmatogenous retinal detachment (RRD; 32 eyes), and macular hole or idiopathic
      epiretinal membrane (controls, 48 eyes) using an enzyme-linked immunosorbent
      assay. RESULTS: Vitreous levels of tenascin-C (median [range]) were significantly
      greater in PVR (845.0 ng/ml [411.0-1,050.0]) than in RRD (21.9 ng/ml [13.2
      127.0]) and in the controls (18.0 ng/ml [9.9-199.0]) (p < 0.0001). CONCLUSION:
      The results indicate the possibility that tenascin-C is involved in the
      pathogenesis of PVR.

PMID- 14573977
TI  - Antibacterial activity of intraocularly used liquids against two strains of
      Pseudomonas aeruginosa.
AB  - The antibacterial effectiveness of liquids used as intraocular tamponading agents
      in vitrectomy was tested in this study. Two strains of Pseudomonas aeruginosa
      were used as challenge organisms: the ATCC 9027 strain and a randomly selected
      resistant strain. The liquid intraocular tamponading agents tested were
      perfluorocarbons, balanced salt solutions, and silicone oils. Perfluorocarbons
      demonstrated a significant decrease in growth of the ATCC 9027 strain and
      sufficient protection against the resistant strain of P. aeruginosa. The balanced
      salt solutions as well as the silicone oils demonstrated insufficient protection
      against both strains used. There is a correspondence of results in the pairs of
      chemically similar substances.

PMID- 14573978
TI  - Prognostic factors in open globe injuries.
AB  - PURPOSES: To evaluate the main factors related to visual outcome after open globe
      injuries (excluding intraocular foreign bodies). METHODS: Retrospective study
      analyzing consecutive ocular lacerations, primarily repaired in this institution,
      between January 1993 and January 2000. Of the 364 cases, 283 (77.75%) lacerations
      were statistically analyzed, correlating the preoperative variables with the
      postoperative visual acuity (VA). Excluded from this study were all patients with
      less than 6 months of follow-up, previous ocular surgery, unreliable information
      on VA, intraocular foreign bodies and endophthalmitis. When a bilateral injury
      was detected, only 1 eye was randomly chosen. RESULTS: It was observed, after
      statistical analysis (multivariate analysis), that the most important factors
      related to postoperative poor VA (less than 20/100) were: the length of the
      laceration, the elapsed time between the injury and the surgery and the presence
      or absence of vitreous loss, cataract (lens damage), hyphema, laceration
      posterior to rectus muscle insertion and retinal detachment. CONCLUSION: With
      this study, it was possible to point out the most important factors related to
      visual prognosis in open globe injuries. The results found are similar to results
      previously reported.

PMID- 14573979
TI  - Pigmented paravenous retinochoroidal atrophy. A literature review supported by
      seven cases.
AB  - Seven patients (4 men and 3 women, ranging in age from 27 to 64 years) with
      pigmented paravenous retinochoroidal atrophy, a rare disorder of unknown origin,
      were studied. The mean follow-up time was 18.5 months. Fundus examinations were
      performed, and color fundus photographs were taken. In addition to fluorescein
      angiography, visual field examinations, color vision and electroretinographic
      tests were performed. All 7 patients were asymptomatic, with visual acuities
      ranging from 3/10 to 10/10. Both fundi showed patches of retinochoroidal atrophy
      and pigmentation along the retinal veins in all patients. Fluorescein angiography
      showed hyperfluorescence due to the pigment epithelial atrophy together with
      hypofluorescence corresponding to bone spicule pigment clumping. Visual field
      tests showed scotomas corresponding with areas of atrophy along the retinal
      veins. The electroretinography showed reduced responses in 2 cases. Color vision
      was normal in all cases. The patients had no history of trauma or a previous
      inflammatory process. Serology for syphilis, Toxoplasma and cytomegalovirus as
      well as a skin test for tuberculosis were negative. When the patients were seen
      at the end of the follow-up period, no variation of the findings was noted.
      Although the fundus abnormalities can be mild or severe, retinal function tests
      indicated that this is a geographic and not a generalized disorder.

PMID- 14573980
TI  - Ocular involvement in leukemia--a study of 288 cases.
AB  - Two hundred and eighty-eight newly diagnosed cases of leukemia (164 males and 124
      females, 167 adults and 121 children, 245 acute and 43 chronic, 151 myeloid and
      137 lymphoid), aged between 6 weeks and 78 years, were examined for eye changes
      in the oncology wards within 2 days of diagnosis before starting chemotherapy.
      Ocular lesions were present in 102 patients (35.4%)--retinal vascular changes in
      91 (31.6%); infiltration of ocular tissues in 5 (1.7%), and neuro-ophthalmic
      signs in 6 (2.1%) cases. Some of the patients had more than one ocular lesion in
      one or both eyes. The eye changes were seen more often in adults (49.1%) than in
      children (16.5%), and in myeloid leukemia (41.0%) than in lymphoid leukemia
      (29.2%). Eye symptoms were present in 29 patients (10%) at initial diagnosis.
      Since ocular lesions were detected in many asymptomatic leukemia patients, eye
      examination should be included as a part of routine evaluation at initial
      diagnosis in these patients.

PMID- 14573981
TI  - Asymptomatic cytomegalovirus retinitis after cardiac transplantation.
AB  - PURPOSE: To determine the prevalence and the risk factors of cytomegalovirus
      (CMV) retinitis after cardiac transplantation in visually asymptomatic patients.
      METHODS: Ophthalmoscopic examinations including fundus fluorescein angiography
      were performed in asymptomatic patients who had cardiac transplantation at Ege
      University Hospital between April 1998 and June 2002 to screen for evidence of
      diagnostic CMV retinitis lesions to determine the prevalence in this population.
      RESULTS: Thirteen patients (aged 40 +/- 12.6) who had cardiac transplantation
      underwent ophthalmoscopic examination 2-50 months (23.5 +/- 16.2 months; mean +/-
      SD) after transplantation. All recipients had positive serology to CMV before
      transplantation. During the study period, 3 patients developed asymptomatic CMV
      reactivation. One patient developed CMV disease (pneumonia). All of the patients
      were visually asymptomatic during the study period. Two patients (15%) had a
      history of diabetes mellitus and chronic severe arterial hypertension. Seven
      recipients (53%) had been heavy cigarette smokers and 3 patients (23%) had
      hyperlipidemia. Two (15%) of 13 patients with arterial hypertension and diabetes
      had evidence of asymptomatic active CMV retinitis. These patients were treated
      with intravenous ganciclovir. CONCLUSIONS: Active cytomegalovirus retinitis
      lesions were found in 2 (15%) of 13 cardiac transplantation patients who had no
      visual symptoms. We think that the patients with systemic microvascular risk
      factors such as diabetes, hypertension and smoking should be screened closely for
      the development of CMV retinitis after cardiac transplantation even if the
      patients have no visual symptoms.

PMID- 14573982
TI  - Transient raise of endothelin-1 plasma level and reduction of ocular blood flow
      in a patient with optic neuritis.
AB  - PURPOSE: To analyze how far an ischemic component might have been involved in
      optic neuritis. METHODS:  CASE REPORT: a 32-year-old man with symptoms
      characteristic for optic neuritis underwent extensive clinical,
      laboratory/serological and vascular examination for systemic associations and
      vascular involvement. RESULTS: The patient was found to have a temporary ocular
      blood flow dysregulation and increased plasma endothelin-1 levels which decreased
      after the acute phase of the optic nerve. CONCLUSIONS: We conclude that there
      might be an ischemic component in this patient with optic neuritis and
      hypothesize that this ischemic component is at least in part due to a temporarily
      increased endothelin-1 level.

PMID- 14573983
TI  - Conjunctival rotation autograft.

PMID- 14573984
TI  - Shared territories: an element of culturally sensitive practice.
AB  - Culturally sensitive practice is expected of all professionals whether working
      domestically or internationally. This essay explores concepts relative to such
      practice, specifically discussing 'shared territories', multidimensionality,
      partnership, and ethnocentrism, and arguing for a view that places all of
      humanity in the diversity mix. The author writes out of her role as an
      academician with responsibilities for preparing students for future practice.

PMID- 14573985
TI  - Cross-cultural practice: what is it really about?
AB  - The idea of cross-cultural practice, as it occurs between practitioners and their
      clients, is problematical. The notion of culture is analysed relative to our
      professions' theories of knowledge production. Practitioners use 'culture' to
      refer to 'linguistic', 'racial', and 'ethnic' factors. An alternative, wider
      definition of what constitutes culture is offered in this paper. Furthermore,
      cross-cultural practice is evaluated against our dominant use of an empirical
      science to understand people and their lives. An analysis of the processes we use
      within our clinical relationship is provided. Empirical processes (disothering,
      reductionism, and essentialism) are discussed and evaluated for their
      coincidental relationship to colonial thinking about culture. A theoretical
      framework referred to as the Relationship of Labouring Affinities is introduced
      as a conceptual alternative to re-position how practitioners work with their
      clients.

PMID- 14573987
TI  - Use of a consensus building approach to plan speech services for children with
      cleft palate in India.
AB  - Cleft lip and palate (CLP) is a common birth defect worldwide. While surgical
      repair can normalize appearance, debilitating speech disorders frequently
      persist. Speech-language pathology (SLP) services are needed to address these
      disorders. However in many regions of the world, there is no discipline of SLP or
      inadequate numbers of trained clinicians. New models for service delivery must be
      explored to address the needs of children with CLP. Community-based
      rehabilitation (CBR) programs represent one model that has been successful in the
      delivery of other rehabilitation services. This paper presents the outcome of a
      consensus workshop held in India that explored the application of the CBR model
      to address the need for SLP services for children with CLP when traditional SLP
      services are limited or not available.

PMID- 14573986
TI  - Considerations in participatory action research when working cross-culturally.
AB  - Professionals from minority world nations are increasingly consulting with
      majority world nations to develop intervention and educational training programs,
      yet minority world programs cannot be simply transferred to majority world
      countries. Participatory action research (PAR) provides a methodology that can be
      used to facilitate the development of programs that are useful for and
      sustainable by the majority world communities. This article describes the
      principles of PAR and gives examples of the ways that cultural values and
      behaviors may influence interactions between minority and majority world persons.
      An understanding of these cultural variations in values is essential for the
      successful implementation of PAR and will reduce miscommunication and incorrect
      interpretations of behaviors.

PMID- 14573988
TI  - Teaching speech and language therapists in Sri Lanka: issues in curriculum,
      culture and language.
AB  - This paper draws on the experiences of the authors in designing and teaching a
      new course to educate speech and language therapists in Sri Lanka. This was the
      first speech and language therapist course in the country and was the result of
      collaboration between two universities, one in the UK and one in Sri Lanka.
      Rather than replicating established programmes elsewhere it was more appropriate
      to design a new course, suited to providing a comprehensive model of service,
      encompassing both social and medical approaches to rehabilitation. Issues about
      developing teaching and learning approaches to match pre-existing knowledge and
      experience of both staff and students are addressed. The particular ways of
      designing the programme to take account of cultural and language aspects of the
      Sri Lankan context are discussed.

PMID- 14573989
TI  - Preliminary planning for training speech and language therapists in Uganda.
AB  - Country-specific issues affect both the implementation of services for people
      with communication disabilities and the training of specialists who provide these
      services. Uganda is a majority world country with an extremely limited specialist
      service, but is looking to expand it by developing training for specialist
      workers. This paper reports on the initial processes adopted in Uganda to develop
      such training. A workshop that brought together all the stakeholders identified
      key issues. The paper relates these issues to the International Association of
      Logopedics and Phoniatrics guidelines for education and training and makes
      suggestions for the way forward.

PMID- 14573990
TI  - International and cross-cultural issues: six key challenges for our professions.
AB  - This paper discusses a number of key challenges facing professionals who work
      with people who have communication disabilities. The challenges are related to
      working internationally and in a cross-culturally competent way. Each challenge
      is discussed, drawing on material from a range of sources, including the papers
      in the final 2003 edition of FOLIA PHONIATRICA ET LOGOPAEDICA ('International and
      Cross-Cultural Issues'). The challenges discussed cover how experiences from
      majority world countries can be used to benefit services elsewhere,
      'mainstreaming' commitment to cross-cultural competence, learning from
      relationships with other professionals, influencing research practice, responding
      to requests to work internationally and finally, dealing with cultural
      differences that challenge working practices. Some solutions are suggested and
      additional questions posed.

PMID- 14573991
TI  - Firing properties and dye coupling of neurons in the pigeon nucleus semilunaris.
AB  - Our previous study indicated that the nucleus semilunaris in birds is a visual
      center. The present study using pigeon brain slices shows that 84 semilunar cells
      examined could be grouped into five types according to responses to depolarizing
      current injections. Type I cells (early bursting, 44%) fire a single burst
      followed by regular spiking. Type II cells (regular spiking, 13%) regularly
      produce spikes, the rates of which are enhanced as currents are increased. Type
      III cells (bursting, 17%) discharge a series of bursts each consisting of 2-4
      spikes. Type IV cells (dual spiking, 15%) evoke both spikes and spikelets. Type V
      cells (inhibition-following, 11%) are characterized by regular spiking followed
      by an inhibitory period after current cessation. Morphologically, semilunar
      neurons have piriform, round, or fusiform somata of 12-23 mum in diameter, which
      give rise to 2-4 primary dendrites with sparse branches. Dual spiking activity is
      invariably correlated with dye coupling, and bursting cells have a tendency to be
      fusiform in shape. Other types of semilunar cells do not show a correlation
      between their firing patterns and morphological features.

PMID- 14573992
TI  - Topography of photoreceptors and retinal ganglion cells in the spotted hyena
      (Crocuta crocuta).
AB  - The spatial distributions of photoreceptors and retinal ganglion cells were
      examined in the spotted hyena (Crocuta crocuta). Two populations of cones were
      identified by immunocytochemical labeling. The hyena retina contains
      approximately 2.3 million middle- to long-wavelength sensitive (M/L) cones that
      reach peak densities of about 7,500/mm(2) in the vicinity of the optic nerve
      head. A sparser population of short-wavelength sensitive (S) cones, totaling
      about 0.3 million, was also detected. There is a striking disparity in the
      spatial distributions of the two cone types with S cones achieving peak density
      in a region located well below the optic nerve head. The differences in the
      spatial distributions of the two cone types have implications both for visual
      sensitivity and for color vision. Hyena rods outnumber cones by about 100:1 with
      rod density falling off modestly along a central-peripheral gradient. Ganglion
      cells were identified in retinal wholemounts by Nissl staining patterns. Their
      distribution defines a prominent visual streak with highest spatial packing
      (approx. 4,200/mm(2)) in an area centralis that is located in the temporal
      retina. The total number of ganglion cells is estimated at about 260,000. Using
      standard assumptions the maximum spatial resolution of the spotted hyena is
      calculated to be about 8.4 cycles/degree, a value similar to estimates obtained
      for other terrestrial carnivores.

PMID- 14573993
TI  - Cell proliferation during early hindbrain development in Alligator.
AB  - Cell proliferation, as determined by immunoreactivity to proliferating cell
      nuclear antigen (PCNA) was investigated during early hindbrain development in
      Alligator. At the earliest stage examined, stage 3, when five rhombomeres are
      present, PCNA immunoreactivity is more robust laterally towards the pial margin
      and interrhombomeric boundaries are clearly seen. Subsequently, PCNA
      immunoreactivity fills each respective rhombomere and increases in intensity but
      respects the boundaries between segments until stage 7. At this time, borders
      between rhombomeres become less distinct. At stage 8, when the full compliment of
      rhombomeres is present, two longitudinal columns of PCNA immunoreactivity are
      seen rostrally which coalesce into a single column caudally. Interrhombomeric
      borders are indistinct. Later, at stage 9/10, two longitudinal columns span the
      entire length of the hindbrain and interrhombomeric boundaries remain less clear.
      The more lateral column fades whereas the medial stripe persists through stage
      12. Thereafter, immunoreactivity fades. These observations confirm the findings
      in other species that rhombomeres are centers of cell proliferation. This feature
      is most likely common to hindbrain development in all gnathostomes. It is
      hypothesized that these two longitudinal columns of cell proliferation might be
      important for future patterning of the hindbrain.

PMID- 14573994
TI  - Input and output characteristics of collision avoidance behavior in the frog Rana
      catesbeiana.
AB  - Input and output characteristics of collision avoidance behavior in the bullfrog
      were examined using computer graphics to model a looming stimulus. The means of
      time-to-collision of avoidance behavior in response to looming visual stimuli
      approaching at a velocity of either 2 or 4 m/s were significantly different
      (t141) = 7.93, p < 0.05). On the other hand, mean threshold sizes of visual
      stimuli triggering avoidance behavior were not significantly different in either
      case (t201) = 0.54, p > 0.05). Furthermore, we showed that the mean threshold
      sizes changed in a predictable manner depending on the distance between the
      displayed stimulus and the animal. These results strongly suggest that the frog
      displays collision avoidance behavior when the visual angle of a looming object
      reaches a constant value (about 20 degrees ). The mean maximum velocities of the
      avoidance behavior in response to the two visual stimuli were not significantly
      different (t198) = 1.44, p > 0.05). However, we found that the frog could control
      the velocity depending on the location of an approaching object in its dorsal
      visual field. Finally, we demonstrated that habituation significantly affected
      the mean probability of avoidance behavior occurrence (ANOVA, at 2 m/s, F(2,15) =
      14.25; at 4 m/s, F(2,15) = 13.35, p < 0.05), but not those of time-to-collision,
      threshold size and maximum velocity (ANOVA, at 2 m/s, F(2,13) = 0.07, F(2,14) =
      0.46 and F(2,14) = 0.70, respectively; at 4 m/s, F(2,15) = 0.50, F(2,14) = 0.68
      and F(2,14) = 0.41, respectively, p > 0.05). Thus, frog collision avoidance
      behavior seems to have an all or none-like property.

PMID- 14573995
TI  - Retinal topography of the harp seal Pagophilus groenlandicus.
AB  - The total number, size, topographic distribution, and cell density of ganglion
      cells were studied in retinal wholemounts of the harp seal Pagophilus
      groenlandicus. Ganglion cell size varied from 10 to 60 mum. A distinct group were
      large ganglion cells more than 30-35 mum in diameter which were similar to alpha
      cells known in terrestrial mammals. The number of alpha-cells constituted 5.3
      5.9% of the total ganglion cell population. The cell size distribution was
      bimodal, with the second mode composed of alpha-cells. The topographic
      distribution of ganglion cells showed a definite area of high cell density
      similar to area centralis of terrestrial carnivores. This area was located in the
      temporal retinal quadrant, 7-8 mm (16-18 degrees ) from the optic disk. In this
      area, the peak cell densities in two wholemounts were 2,500 and 1,650 (mean
      2,075) cells/mm(2). With a posterior nodal distance of 25.5 mm (underwater), this
      density corresponded to 495 and 327 (mean 411) cells/deg(2). These values predict
      a retinal resolution of 2.7-3.3' (11.1-9.0 cycles/deg) in water and 3.6-4.4' (8.3
      6.8 cycles/deg) in air. Topographic distributions of alpha-cells was
      qualitatively similar to that of the total ganglion cell population, but the
      density of alpha-cells constituted only a few percent (mostly 3-7.5%) of the
      total ganglion cell density.

PMID- 14573996
TI  - Spatial distribution and morphological characteristics of the trunk lateral line
      neuromasts of the sea bass (Dicentrarchus labrax, L.; Teleostei, Serranidae).
AB  - The morphology and spatial distribution of the different types of neuromasts
      encountered on the trunk lateral line of the sea bass (Dicentrarchus labrax) were
      examined using scanning electron microscopy. The sea bass trunk lateral line
      exhibits a complete straight pattern. In their basic features, the two types of
      neuromasts present, canal and superficial, resemble what has been described in
      other fishes. They are similar in their general cellular organization but differ
      in sizes, and shapes, as well as in the densities and lengths of their hair
      bundles. However, the sea bass trunk lateral line distinguishes itself in several
      ways. For instance, the pores of the canal segments are partially obstructed due
      to the overlap of scales throughout the trunk. Moreover, based on the density and
      length of the hair bundles, two distinct areas, central and peripheral, could be
      distinguished within the maculae of canal neuromasts. Their cupulae are also
      peculiar as they possess two wing-like extensions and that their central core
      appears to be organized in layers instead of columns. In addition, the
      superficial neuromasts, up to 6 per scale, are either round or elliptical and
      seem to be distributed serendipitously. Finally, within the maculae of both types
      of neuromasts, a significant number of hair bundles do not follow the two
      directional polarity pattern usually described. Although some hypotheses are
      proposed, the influence of these characteristics in terms of signal encoding and
      fish behavior is yet to be understood.

PMID- 14573997
TI  - Carvedilol, an antihypertensive drug with antioxidant properties, protects
      against glycerol-induced acute renal failure.
AB  - BACKGROUND/AIMS: The pathogenesis of glycerol-induced myoglobinuric acute renal
      failure involves, among other causes, ischaemia, vascular congestion and reactive
      oxygen metabolites. The aim of this study was to investigate the role of
      carvedilol, an antihypertensive drug with antioxidative potential, in glycerol
      induced acute renal failure in rats. METHODS: Three groups of rats were employed
      in this study. Group 1 served as control, group 2 was given 50% glycerol (8
      ml/kg, i.m.) and group 3 was given glycerol plus carvedilol (3 mg/kg, i.p.).
      Renal injury was assessed by measuring plasma creatinine, blood urea nitrogen,
      creatinine and urea clearance. The oxidative stress was measured by renal
      malondialdehyde levels, reduced glutathione levels and enzymatic activity of
      catalase, glutathione reductase and superoxide dismutase. RESULTS: Glycerol
      treatment resulted in marked renal oxidative stress and significantly deranged
      renal functions. Both of these factors were significantly improved by carvedilol
      treatment. Carvedilol, by its interaction with Fenton reaction chemistry and
      radical scavenging activity, protected the kidney against the oxidative stress
      and resultant renal dysfunction produced by glycerol. CONCLUSION: Based on these
      results, this study indicates the protective effect of carvedilol in this
      rhabdomyolysis-mimicking model.

PMID- 14573998
TI  - Prevention of hypertension attenuates albuminuria and renal expression of
      fibronectin in diabetic spontaneously hypertensive rats.
AB  - BACKGROUND/AIM: The aim of this study was to evaluate the effect of preventing
      hypertension on renal disease in a model of genetic hypertension and diabetes.
      METHODS: Four-week-old spontaneously hypertensive rats (SHR) with streptozotocin
      induced diabetes were randomized for no treatment, or for treatment with
      captopril, losartan or triple therapy (hydrochlorothiazide, reserpine and
      hydralazine) for 16 weeks. RESULTS: Increase in systolic blood pressure was
      equally prevented by captopril (128 +/- 3 mm Hg), losartan (128 +/- 2) and triple
      therapy (129 +/- 2, p < 0.0001). Albuminuria was similarly reduced by captopril
      (499 (404-659)), losartan (622 (470-976)) and triple therapy (479 (362-600)
      microg/24 h (p < 0.0001)). Renal fibronectin expression increased in diabetic SHR
      (125 +/- 13 densitometric unit) as compared to the controls (51 +/- 9, p <
      0.0001), and decreased (p < 0.0001 vs. diabetic SHR) with captopril (32 +/- 8),
      losartan (27 +/- 4) and triple therapy (35 +/- 6). CONCLUSION: The prevention of
      hypertension in diabetic SHR by captopril, losartan or triple therapy was equally
      efficacious in impeding increase of albuminuria and the expression of renal
      fibronectin. Under these conditions, tight blood pressure control was the main
      determinant in attenuating nephropathy.

PMID- 14573999
TI  - Familial breast cancer: an investigation into the outcome of treatment for early
      stage disease.
AB  - The purpose of this study was to retrospectively compare the outcomes of
      treatment in 304 women with familial and sporadic breast cancer to clarify the
      options for the primary management of familial breast cancer. The majority of
      women were consecutively ascertained on the basis of either breast cancer
      diagnosed at age < 40 years or bilateral breast cancer. In addition, known BRCA1
      mutation carriers were identified through the genetics services in participating
      centres. These patients were subdivided into those with a significant family
      history of breast cancer or known BRCA1 mutation (FH+) and those with no
      significant family history (FH-). There were no significant differences in age,
      surgical treatment or adjuvant treatment between the two groups, but there were
      significantly more women whose nodal status was unknown in the FH+ group.
      Ipsilateral recurrence occurred in 22.2% of FH+ patients compared with 24.1% of
      FH- patients (p = 0.774) who underwent breast conserving surgery. There was a
      striking excess of contralateral breast cancers in the FH+ group (35.9% v 16%, p
      = 0.0007), with a cumulative risk of contralateral cancer of 36% at 10 years.
      This was reflected in a non-significant trend toward worse relapse free survival
      in the FH+ group (p = 0.0563), but no difference was observed in overall survival
      between the two patient groups (p = 0.142). Similarly, for patients with known
      BRCA1 mutations, contralateral recurrence occurred more frequently, but other
      outcomes were not significantly different from the FH- group. Breast conserving
      treatment is not associated with an increased risk of local recurrence in women
      with familial breast cancer and the prognosis of these women appears to be
      similar to that of young women with apparently sporadic breast cancer. However,
      the risk of contralateral breast cancer is significant in the FH+ group and
      should be considered in planning primary treatment and follow up.

PMID- 14574000
TI  - Commentary on Eccles et al.: familial breast cancer: an investigation into the
      outcome of treatment for early stage disease.

PMID- 14574001
TI  - Familial adenomatous polyposis at the Tel Aviv Medical Center: demographic and
      clinical features.
AB  - Familial adenomatous polyposis (FAP) is an uncommon, but widespread genetic
      disorder that develops multiple colonic adenomatous polyps and, if untreated, can
      lead to large bowel cancer. Little is known about its occurrence and
      characteristics in the Israeli population. AIMS: To evaluate FAP prevalence,
      phenotypic manifestations and compliance for diagnosis and follow-up in our
      registry. METHODS: Since 1993 approximately one-half of FAP patients in Israel
      have been seen and followed-up by us before and/or after colectomy. They and
      their families were encouraged to have mutation analysis, genetic and/or
      endoscopic screening. RESULTS: 37 pedigrees were identified, including 2 non
      Jewish. The Jewish ethnic distribution was similar to that of the general
      population and the point prevalence rate estimated as 28.4/one million Jewish
      inhabitants. There were 461 first-degree relatives at-risk for FAP. Genetic
      screening was completed and successful in 28 pedigrees (87.5%), and 73 FAP
      patients entered the registry. Marked intra- familial phenotypic variations with
      minimal disease manifestation were noted in 11 patients belonging to 4 pedigrees.
      Cancer occurred in 15.1% (11 patients), in 10 before FAP diagnosis or during
      follow- up elsewhere, but one non-compliant patient developed duodenal cancer.
      One other patient died from a massive, neglected, intra- abdominal desmoid.
      Compliance for evaluation and follow-up of pedigree members and individual FAP
      patients was inadequate in 29% and 27%, respectively. CONCLUSIONS: FAP occurs in
      the Israeli Jewish population at the expected rate, but is inadequately
      recognized in non-Jews. The inadequate compliance for screening and post-surgical
      follow-up needs to be addressed by educating the public, health care workers and
      Health Insurers.

PMID- 14574002
TI  - FAP associated thyroid carcinoma in mother and her daughter.
AB  - A 21 year-old Japanese female was referred to the hospital for evaluation of a
      mass in her neck. Cytologic samples obtained through fine needle aspiration (FNA)
      material from the mass showed pseudopapillary or sheet-like clusters. The cells
      had oval nuclei and columnar cytoplasms. Nuclear groove and intranuclear
      inclusions were scarcely seen. The cells had a cribriform or solid pattern,
      unlike cells in papillary thyroid carcinoma. This distinct cytological appearance
      is thought to belong to FAP (familial adenomatous polyposis)-associated thyroid
      cancer. The patient was diagnosed with FAP associated papillary thyroid
      carcinoma. FAP was confirmed by colonoscopy. Her mother, 48 years old, also
      detected an anterior neck swelling at the time of her daughter's admission. At
      the age of ten, the mother had undergone total colectomy because of FAP. FNA of
      the mass demonstrated the same cytological appearance as from her daughter's
      tumor. Total thyroidectomy was performed. Gross and microscopic appearances of
      the tumor was similar in mother and daughter. We believe it is possible to detect
      FAP through FNA cytology of thyroid tumors if pathologists are aware of the
      unique cytohistological features of thyroid tumor cells in FAP.

PMID- 14574004
TI  - Mutations of the 'minor' mismatch repair gene MSH6 in typical and atypical
      hereditary nonpolyposis colorectal cancer.
AB  - Mutations of the mismatch repair (MMR) genes MLH1 and MSH2 are associated with
      hereditary nonpolyposis colorectal cancer (HNPCC), a highly penetrant autosomal
      dominant condition characterized by hypermutability of short tandemly repeated
      sequences in tumor DNA. Mutations of another MMR gene, MSH6, seem to be less
      common than MLH1 and MSH2 defects, and have been mostly observed in atypical
      HNPCC families, characterized by a weaker tumor family history, higher age at
      disease onset, and low degrees of microsatellite instability (MSI), predominantly
      involving mononucleotide runs. We have investigated the MSH6 gene sequence in the
      peripheral blood of 4 HNPCC and 20 atypical HNPCC probands. Two frameshift
      mutations within exon 4 were detected in 2 patients. One mutation was found in a
      proband from a typical HNPCC family, who had developed a colorectal cancer (CRC),
      a gastric cancer and a rectal adenoma. The CRC and the adenoma showed mild MSI
      limited to mononucleotide tracts, while the gastric carcinoma was microsatellite
      stable. The other mutation was detected in an atypical HNPCC proband, whose CRC
      showed widespread MSI involving both mono- and dinucleotide repeats. The
      phenotypic variability associated with MSH6 constitutional mutations represents a
      complicating factor for the optimization of strategies aimed at identifying
      candidates to MSH6 genetic testing.

PMID- 14574005
TI  - Cafe-au-lait spots and early onset colorectal neoplasia: a variant of HNPCC?
AB  - BACKGROUND: Cafe-au-lait spots (CALS) are classically found in neurocutaneous
      syndromes such as neurofibromatosis, but have not been associated with hereditary
      colorectal cancer. However, review of hereditary colorectal cancer case reports
      reveals occasional description of CALS on physical exam. METHODS: We describe the
      colonic and extracolonic phenotype in a family with CALS and early onset
      colorectal neoplasia (adenomas and/or cancer) and review 23 additional families
      reported in the literature. RESULTS: Among the 24 families, 32/59 (54.2%)
      individuals had colorectal adenomas diagnosed at a mean age of 15.7 +/- 1.1 (SE)
      years (range 5-38 years). The majority (24/32, 75.0%) of persons at first
      colorectal examination had oligopolyposis (< 100 polyps) versus polyposis (> or =
      100 polyps). Forty-two of 59 (71.2%) individuals were affected with colorectal
      cancer, diagnosed at a mean age of 31.9 +/- 2.7 years (range 5-70 years). A brain
      tumor was found in 28/59 (47.5%) affected individuals (4 families with 2 or more
      cases) with an overall mean age of diagnosis of 16.5 +/- 1.2. Lymphoma and/or
      leukemia was found in 8/24 (33.3%) families (one family with 3 cases). Two
      families had mutation of the mismatch repair gene, hPMS2 (1 with homozygous
      germline mutation), while two carried homozygous germline mutations of another
      mismatch repair gene, hMLH1. CONCLUSIONS: Cafe-au-lait spots with early onset
      colorectal neoplasia may identify families with a variant of HNPCC characterized
      by oligopolyposis, glioblastoma at young age, and lymphoma. This variant may be
      caused by homozygous mutation of the mismatch repair genes, such as hPMS2 or
      hMLH1.

PMID- 14574003
TI  - The reliability of immunohistochemistry as a prescreening method for the
      diagnosis of hereditary nonpolyposis colorectal cancer (HNPCC)--results of an
      international collaborative study.
AB  - Hereditary nonpolyposis colorectal cancer syndrome (HNPCC) is an autosomal
      dominant condition accounting for 2-5% of all colorectal carcinomas as well as a
      small subset of endometrial, upper urinary tract and other gastrointestinal
      cancers. An assay to detect the underlying defect in HNPCC, inactivation of a DNA
      mismatch repair enzyme, would be useful in identifying HNPCC probands. Monoclonal
      antibodies against hMLH1 and hMSH2, two DNA mismatch repair proteins which
      account for most HNPCC cancers, are commercially available. This study sought to
      investigate the potential utility of these antibodies in determining the
      expression status of these proteins in paraffin-embedded formalin-fixed tissue
      and to identify key technical protocol components associated with successful
      staining. A set of 20 colorectal carcinoma cases of known hMLH1 and hMSH2
      mutation and expression status underwent immunoperoxidase staining at multiple
      institutions, each of which used their own technical protocol. Staining for hMSH2
      was successful in most laboratories while staining for hMLH1 proved problematic
      in multiple labs. However, a significant minority of laboratories demonstrated
      excellent results including high discriminatory power with both monoclonal
      antibodies. These laboratories appropriately identified hMLH1 or hMSH2
      inactivation with high sensitivity and specificity. The key protocol point
      associated with successful staining was an antigen retrieval step involving heat
      treatment and either EDTA or citrate buffer. This study demonstrates the
      potential utility of immunohistochemistry in detecting HNPCC probands and
      identifies key technical components for successful staining.

PMID- 14574006
TI  - Chemotherapy resistant ovarian cancer in carriers of an hMSH2 mutation?
AB  - Hereditary Non-Polyposis Colorectal Cancer (HNPCC, Lynch syndrome) is an
      autosomal dominant condition of cancer susceptibility with high penetrance,
      characterised by early onset of colon tumours as well as a variety of
      extracolonic tumours including ovarian cancer and, in particular, cancer of the
      endometrium. Germline mutations in one of five DNA-mismatch repair (MMR) genes
      (hMLH1, hMSH2, hMSH6, PMS1, PMS2) are known to cause HNPCC. To date, mutations in
      two of these genes (hMSH2 and hMLH1) are found in the majority of mutation
      positive families. Recent literature suggests that especially hMSH2 mutations are
      associated with extracolonic tumours. We describe two women from an HNPCC family
      carrying an hMSH2 mutation (deletion of exon 6 of this gene) who developed
      ovarian cancer. In these patients (full cousins) the ovarian cancers were noted
      for their aggressive development and rapid recurrence after surgical debulking
      and during regular multichemotherapy including Cisplatin. This report strengthens
      recent in vitro studies suggesting an involvement of MMR-gene mutations in
      ovarian cancer cell biology with decreased susceptibility to Cisplatin therapy.
      The possible implications for the therapy of ovarian cancer, the screening and
      genetic counselling of family members are discussed.

PMID- 14574007
TI  - Desmoid tumour in familial adenomatous polyposis. A review of literature.
AB  - Desmoid tumours (DT) are rare benign tumours that do not metastasise, but tend to
      invade locally. DT are frequently seen in patients with familial adenomatous
      polyposis (FAP), and diagnosis and treatment are often difficult. Surgical
      trauma, genetic predisposition and hormonal factors are considered to be
      correlated with the development and growth of DT. In patients with FAP, 50% of
      the tumours are localised intra-abdominally, and 85-100% of these are mesenteric.
      DT frequently present as non- tender, slowly growing masses. The symptoms are
      abdominal pain, vomiting, diarrhoea or haematochezia. Mesenteric DT can cause
      small bowel obstruction or ischaemia, hydronephrosis or form fistulas. Diagnosis
      is obtained through biopsy and the extension is determined by a CT-scan. Surgical
      excision is recommended in patients with DT in the abdominal wall. First line
      treatment of mesenteric DT is a NSAID in combination with tamoxifen. Surgery may
      be considered in case of a small and well-defined DT with no signs of invasion of
      vital structures, and in cases of imminent bowel ischaemia or obstruction. The
      prognosis in mesenteric DT is serious, and improvement of the therapeutic
      strategy awaits current international studies.

PMID- 14574008
TI  - Preventive measures in Peutz-Jeghers syndrome.
AB  - Peutz-Jeghers syndrome is a rare genetic disorder characterized by mucocutaneous
      melanin deposition, intestinal polyposis and an increased risk of cancer, both
      intestinal and extra-intestinal. We describe the current status of diagnosis and
      the methods by which the consequences of this condition can be minimized. A
      surveillance program for those diagnosed is also included.

PMID- 14574009
TI  - Profuse familial adenomatous polyposis with an adenomatous polyposis coli exon 3
      mutation.
AB  - The attenuated form of familial adenomatous polyposis coli (AAPC) is associated
      with mutations in the adenomatous polyposis coli (APC) gene which cluster in the
      5' region of the gene. It has been proposed that a 'genotype-phenotype boundary'
      exists at codons 159-163, and mutations that are 5' of this boundary will produce
      AAPC. Herein we document a three-generation family with an exon 3 mutation well
      to the 5' side of the proposed boundary, in which two affected individuals have
      had, in their 40s, a profuse form of familial adenomatous polyposis coli. We
      conclude that the codon 159-163 'boundary' is indicative rather than definitive.
      These two patients also had postoperative intra-abdominal adhesions, severely so
      in one.

PMID- 14574010
TI  - Genotype and phenotype in hereditary nonpolyposis colon cancer: a study of
      families with different vs. shared predisposing mutations.
AB  - Hereditary nonpolyposis colorectal cancer (HNPCC) is a multi-organ cancer
      syndrome associated with heritable mutations in DNA mismatch repair genes,
      particularly MLH1 (MutL Homologue 1) and MSH2 (MutS Homologue 2). We took
      advantage of the unique characteristics of the Finnish HNPCC families to assess
      genotype- phenotype correlations in this disorder. We studied 295 mutation
      carriers (10 mutations in MLH1 and 3 in MSH2) segregating in 55 families. In
      addition to the comparison of families with different mutations, the enrichment
      of two MLH1 mutations, one affecting exon 16 (29 families, 186 individuals) and
      another one affecting exon 6 (10 families, 45 individuals) allowed the comparison
      of kindreds with identical predisposing mutations. Extracolonic cancers were more
      common in MSH2 than MLH1 mutation carriers, with the ratios of 0.48 and 0.64,
      respectively, of colorectal cancer to all cancers (P = 0.076). Within MLH1, two
      mutations affecting only the amino terminal portion showed a significant
      association with late onset of cancer as compared to the remaining mutations.
      Importantly, families with the MLH1 exon 16 mutation displayed significant
      variation (P = 0.012) in the age at onset of colon cancer, despite shared
      predisposition. We conclude that even though characteristics of the inherited
      mutations may explain part of the observed clinical variation, other factors have
      a significant impact on HNPCC phenotype determination.

PMID- 14574011
TI  - Double primary cancers of the breast and thyroid in women: molecular analysis and
      genetic implications.
AB  - Multiple primary cancers are characteristic of hereditary cancer syndromes. A
      familial association between breast and thyroid cancer has been suggested, but a
      genetic basis for this association has not yet been established. To determine the
      extent to which double primary cancers of the breast and thyroid are due to
      common hereditary factors, we conducted a registry- and hospital-based study in
      Ontario and Quebec. We obtained family histories of 74 women diagnosed with both
      cancer of the breast and thyroid before 70 years of age. Cancer histories were
      obtained for the 533 first- degree relatives of these women. The observed cancer
      rate in the relatives was compared with the expected number, based on age-
      standardized Canadian cancer incidence rates, and relative risks were estimated.
      A total of 87 cancers were observed in the relatives, compared to 93.7 expected
      cancers, giving a relative risk of 0.9 (95% confidence interval (CI): 0.7-1.1).
      The risk for breast cancer was 1.1 (95% CI: 0.6-1.7) and the risk for thyroid
      cancer was 0.7 (95% CI: 0-3.8). Blood samples were collected on 53 patients for
      mutational analysis of the BRCA1, BRCA2, and PTEN genes. One woman was found to
      be a carrier of a BRCA1 mutation (exon 11 3227delT). Our findings do not support
      the hypothesis that a significant proportion of double primary cancers of the
      breast and thyroid are due to hereditary factors.

PMID- 14574012
TI  - A paradox: urgent BRCA genetic testing.
AB  - Diagnostic or predictive testing for germline mutations in cancer predisposition
      genes is inherently slow as result of both genetic counselling and mutation
      analysis. The overall time taken for mutation testing is not generally perceived
      as harmful to the individual and may be positively beneficial in order to permit
      full reflection on the implication of the genetic test results. However, we
      present three cases where we considered urgent genetic testing for the presence
      of mutations in th BRCA 1 and 2 genes to be necessary as the test result would
      have altered the subsequent clinical management of these individuals or their
      families.

PMID- 14574013
TI  - Women at risk of ovarian cancer: attitudes towards and expectations of the
      familial ovarian cancer clinic.
AB  - Familial ovarian cancer clinics are a recent development and little is known
      about the characteristics of women who attend. One hundred and ninety-seven women
      with a family history of ovarian cancer completed a questionnaire prior to their
      initial attendance at the Familial Ovarian Cancer Clinic in Edinburgh. Issues
      relating to screening procedures were the most commonly cited barriers to
      attendance, with a proportion finding gynaecological examination embarrassing
      (17.0%) or uncomfortable (18.0%). Expectations of the clinic were high in terms
      of access to resources and information. The vast majority of women would prefer
      to have regular screening (94.7%) and genetic testing (93.2%) if it were
      available. Attitudes to prophylactic surgery and chemoprevention were more
      diverse, but would be considered by 54.3% and 43.9% of respondents respectively.
      Although the current screening procedure for ovarian cancer is of unproven
      efficacy, a high proportion of women believed in its ability to reduce mortality
      (77.9%) and to detect tumours at an early stage (65.8%). There was a trend for
      women to believe this more strongly at follow-up. This study highlights the need
      to make women more aware of the limitations of current ovarian cancer screening
      techniques, particularly where the alternative management strategy of
      prophylactic surgery might otherwise be dismissed.

PMID- 14574014
TI  - Cytogenetic characteristics of oral squamous cell carcinomas in Fanconi anemia.
AB  - Fanconi anemia (FA) is an autosomal recessive syndrome with a marked
      predisposition to malignancies, in particular acute myeloid leukemia and squamous
      cell carcinoma of the oral cavity. We examined oral squamous cell carcinoma
      tissue from two FA patients (FA-A and FA-C) by comparative genomic hybridization.
      Both tumors, which were negative for human papilloma as well as Epstein-Barr
      viral sequences, showed multiple alterations with a high proportion of whole-arm
      chromosomal gains and losses. This combination of features as well as the sites
      involved in chromosomal breakage are very similar to what is typically observed
      in non-FA oral tumors. These results suggest that the process leading to early
      occurrence of oral cancer in FA patients follows a similar pathway as in non-FA
      cancer patients, which would support a caretaker function for FA genes in the
      protection against oral carcinogenesis. Since FA patients are uniquely
      hypersensitive to DNA cross-linking agents, while oral cancer in the general
      population is thought to be environmentally induced, these results also suggest
      that environmental DNA cross-linkers may be causally involved in oral
      carcinogenesis.

PMID- 14574015
TI  - Population-based study of familial medullary thyroid cancer.
AB  - BACKGROUND: We wanted to carry out a population-based study on medullary thyroid
      cancer (MTC) in order to quantify familial risks. METHODS: MTC was studied in the
      Swedish Family-Cancer Database, updated in 1999 to cover individuals and
      offspring, born after 1934 with their biological parents, totaling 9.6 million
      persons. Cancer data were obtained from the Swedish Cancer Registry from year
      1958 to 1996 and included 2,435 thyroid cancers among offspring. RESULTS: 65
      offspring were identified with MTC, which was coded as a separate entity since
      1985. 62% had neither affected parent nor sib. Most familial cases were diagnosed
      at ages 15 to 24 and sporadic cases 25 years later. The familial SIRs of MTC were
      3,080 and 3,650 when either a parent or a sib had MTC; when both had MTC the SIR
      was 35,800. All the familial risks were highest in young age groups, 0-9 years.
      MEN 2 or MEN 2-like families were considered when one family member had a TC and
      an adrenal pheochromocytoma. SIR of MTC in offspring was 61,000 when a parent had
      a MEN 2-like cancer and a sib had MTC. CONCLUSIONS: We described familial and
      sporadic MTC in a population-based database. The familial risks of MTC may be the
      highest ever reported in population based studies.

PMID- 14574016
TI  - Familial cancer database: a clinical aide-memoire.
AB  - Cancer is associated with a wide range of hereditary disorders. Recognizing these
      disorders in cancer patients may be of great importance for the medical
      management of both patients and their relatives. Conversely, recognizing the fact
      that cancer may develop in patients already diagnosed with a particular
      hereditary disorder may be important for the same reason. We have developed a
      stand-alone interactive computer program, Familial Cancer Database (FaCD), to
      assist the clinician in making a genetic differential diagnosis in cancer
      patients as well as in becoming aware of the tumour spectrum associated with a
      particular hereditary disorder. The program tries to match tumour and non-tumour
      features observed in patients and their families with any of the more than 300
      disorders presently contained in its database and provides a clinical synopsis
      with literature references for each of these disorders. FaCD is offered free of
      charge in support of the Familial Cancer and Prevention project of the UICC
      Cancer Epidemiology and Prevention program. The software is primarily aimed at
      health care professionals with at least a basic knowledge of clinical cancer
      genetics, and can be downloaded from the internet at http://facd.uicc.org.

PMID- 14574017
TI  - Cancer risk in mismatch repair gene mutation carriers.
AB  - Optimally accurate and valid estimates of cancer risk in genetically- defined
      subgroups requires population-based research. For rare genetic traits, very large
      studies are needed. Such is the case in hereditary nonpolyposis colorectal cancer
      syndrome (HNPCC), caused by mutations in mismatch repair (MMR) genes. A
      potentially more efficient approach is genotyped-proband design (GPD), in which
      probands are genotyped and the phenotypes of their relatives are investigated.
      However, to date most information comes from registry-based studies, where
      ascertainment bias makes interpretation difficult. Development in testing
      technology will lead to more identified mutation carriers, producing a clinical
      imperative to estimate risk, despite these problems. We reviewed the available
      results, and concluded that male mutation carriers have a lifetime colorectal
      cancer risk of 74% or more; female mutation carriers have a lower risk which is
      still many times higher than the risk in the general population. Risk is highest
      between the ages of 40 and 60, but considerable even before age 40. Lifetime
      endometrial cancer risk is 42% or more; the highest incidence is between age 40
      and 60, and diagnosis before the age of 35 is rare. MMR mutation carriers are at
      elevated risk for ovarian, gastric, urologic tract, small bowel, hepatobiliary
      tract cancer, and for brain tumors. The risk of these cancer types is much lower
      than the risk for colorectal and endometrial cancer, but accurate, especially age
      related estimates of risk are not available. Prevention strategies depend on
      estimates of age-specific risk. Clearly, multicenter studies to obtain such
      estimates are needed.

PMID- 14574018
TI  - Historical perspectives on interventional electrophysiology.
AB  - The history of interventional electrophysiology is long and fascinating. In the
      beginning, there is not simply the anatomy and physiology of the heart, but also
      analysis of the pulse, which indicates the activity of the heart. The analysis of
      the (peripheral) pulse as a mechanical expression of heart activity goes back
      several millennia. In China, in 280 B.C., Wang Chu Ho wrote ten books about the
      pulse. The Greeks called the pulse "sphygmos", and the sphygmology thus deals
      with a theory of this natural occurrence. In Roman times, Galen interpreted the
      various types of pulse according to the widespread presumption of the time, that
      each organ in every disease has its own form of pulse. The basic tool for
      arrhythmia diagnosis became the electrocardiography introduced by Willem
      Einthoven who obtained the first human electrogram 1902 in Leiden, The
      Netherlands. The growing clinical importance of electrical cardiac stimulation
      has been recognized and renewed as Zoll (1911-1999) in 1952 reported a successful
      resuscitation in cardiac standstill by external stimulation. Meanwhile all over
      the world, millions of patients with cardiac arrhythmias have been treated with
      pacemakers in the last 45 years. The concept of a fully automatic implantable
      cardioverter-defibrillator system (ICD) for recognition and treatment of
      ventricular tachyarrhythmias was first suggested in 1970. The first implantation
      of the device in a human being was performed in February 1980. Further
      developments concern atrial and atrioventricular defibrillators, radiofrequency
      ablation, laser therapy and advanced antiarrhythmic surgery, new antiarrhythmic
      drugs and sophisticated devices for preventive pacing. The advances in the field
      of diagnostic and therapeutic application of pharmacologic and electrical tools
      as well as alternative methods will continue as rapidly as before in order to
      give us further significant aid in taking care of the patient.

PMID- 14574019
TI  - Experimental and clinical AF mechanisms: bridging the divide.
AB  - There is general agreement that AF is most likely a reentrant rhythm disturbance.
      However, the precise pathophysiological bases for its initiation and maintenance
      have not been fully resolved. In the original description of the multiple wavelet
      hypothesis of atrial fibrillation, as put forward by Moe et al. and later
      substantiated by Allessie et al., the wavelets were thought to move randomly
      throughout the atria. However, more recent studies that have applied high
      resolution mapping of wave propagation and rigorous analyses in the time and
      frequency domains to long episodes of AF, have provided evidence that atrial
      fibrillation is not random, but is accompanied by a high degree of spatiotemporal
      periodicity. This has led to the hypothesis that maintenance of AF may depend on
      the uninterrupted periodic activity of a small number of discrete reentrant
      sites, established by the interaction of propagating waves with anatomical
      heterogeneities in the atria. It has been proposed also that the rapidly
      successive wave fronts emanating from these sources propagate through both atria
      and interact with anatomical and/or functional obstacles, leading to
      fragmentation and wavelet formation. In support of this idea, observations made
      during radiofrequency ablation of AF in humans suggest that, in some patients, a
      single, repetitive focal source of activity propagate impulses from an individual
      pulmonary vein to the remainder of the atrium as fibrillatory waves. These
      studies underscore the need for identification of continuing AF sources at
      localized sites, and of transient AF "triggers", which may involve normal or
      abnormal pacemaker mechanisms or even reentrant activity, and of the manner in
      which electrical activity initiated by such triggers interacts with the normally
      propagating electrical waves to initiate fibrillatory activity in the atria.

PMID- 14574020
TI  - Inherited arrhythmia syndromes: applying the molecular biology and genetic to the
      clinical management.
AB  - Thanks to the contribution of molecular genetics, the genetic bases, the
      pathogenesis and genotype-phenotype correlation of diseases such as the Long QT
      syndrome, the Brugada Syndrome, the Progressive cardiac conduction defect
      (Lenegre disease), the Catecholaminergic Polymorphic Ventricular Tachycardia and
      Andersen Syndrome have been progressively unveiled and show an extremely high
      degree of genetic heterogeneity. The evidences supporting this concept are
      outlined with a particular emphasis on the growing complexity of the molecular
      pathways that may lead to arrhythmias and sudden death, in term of the
      relationships between genetic defect(s) and genotype(s) as well as gene-to gene
      interactions. The current knowledge is reviewed, focusing on the evidence that a
      single clinical phenotype may be caused by different genetic substrates and,
      conversely, a single gene may cause very different phenotypes acting through
      different pathways.

PMID- 14574021
TI  - Detection of the fingerprint of the electrophysiological abnormalities that
      increase vulnerability to life-threatening ventricular arrhythmias.
AB  - Reduction of sudden death requires accurate identification of patients at risk
      for ventricular tachycardia (VT) and effective therapies. The Multicenter
      Unsustained Tachycardia Trial and Multicenter Automatic Defibrillator
      Implantation Trials demonstrate that the implantable cardioverter defibrillator
      impacts favorably on the incidence of VT in patients with myocardial infarction,
      underscoring the need to detect the electrophysiologic abnormalities required for
      the development of VT. Methods used for this purpose include: Holter monitoring,
      ejection fraction, signal-averaged ECG, heart rate variability, T-wave alternans,
      baroreflex sensitivity, and programmed stimulation. Performance of each method
      alone has demonstrated high-negative but low-positive predictive values. Recent
      studies confirm that their use in combination augments performance.A second
      approach for improving performance has been to reexamine how well each method
      detects the electrophysiological derangements that lead to VT. Our recent work
      has focused on the signal-averaged ECG. Judging from transmural maps of
      ventricular activation during VT and sinus rhythm obtained from patients, late
      potentials fail to detect completely signals from myocardium responsible for VT.
      To obviate this limitation we developed an approach based on inferred epicardial
      potentials in the frequency domain from 190-surface ECGs using individualized
      heart-torso models. Torso geometry and electrode positions are measured with a 3
      armed digitizer. The location of cardiac structures is determined using
      echocardiography. The pericardial surface is approximated by a sphere that
      encloses the heart. Epicardial potentials are inferred using the boundary element
      method with zero-order Tikhonov regularization and the Composite Residual
      Smoothing Operator over the QRS complex. Studies are underway to determine if
      analysis of bioelectrical signals enveloping arrhythmogenic tissue improves
      identification of patients vulnerable to VT.

PMID- 14574022
TI  - Toward an understanding of the molecular mechanisms of ventricular fibrillation.
AB  - A major goal of basic research in cardiac electrophysiology is to understand the
      mechanisms responsible for ventricular fibrillation (VF). Here we review recent
      experimental and numerical results, from the ion channel to the organ level,
      which might lead to a better understanding of the cellular and molecular
      mechanisms of VF. The discussion centers on data derived from a model of stable
      VF in the Langendorff-perfused guinea pig heart that demonstrate distinct
      patterns of organization in the left (LV) and right (RV) ventricles. Analysis of
      optical mapping data reveals that VF excitation frequencies are distributed
      throughout the ventricles in clearly demarcated domains. The highest frequency
      domains are usually found on the anterior wall of the LV, demonstrating that a
      high frequency reentrant source (a rotor) that remains stationary in the LV is
      the mechanism that sustains VF in this model. Computer simulations predict that
      the inward rectifying potassium current (IK1) is an essential determinant of
      rotor stability and rotation frequency, and patch-clamp results strongly suggest
      that the outward component of the background current (presumably IK1) of cells in
      the LV is significantly larger in the LV than in the RV. These data have opened a
      new and potentially exciting avenue of research on the possible role played by
      inward rectifier channels in the mechanism of VF and may lead us toward an
      understanding of its molecular basis and hopefully lead to new preventative
      approaches.

PMID- 14574023
TI  - Genetic polymorphisms, drugs, and proarrhythmia.
AB  - Humans vary widely in their response to drug therapy. This may reflect
      variability in the relationship between a drug dose and the concentrations of
      drug and metabolite(s) at relevant target sites; this is termed pharmacokinetic
      variability. Another mechanism is that individuals vary in their response to
      identical exposures to drug (pharmacodynamic variability). In this case, there
      may be variability in the target molecule(s) with which a drug interacts, or more
      generally in the broad biologic context in which the drug-target interaction
      occurs; for example, ischemia, electrolyte disturbances, or hypertrophy can all
      modulate drug effects. Variants in the genes encoding proteins important for
      pharmacokinetics or for pharmacodynamics have now been described as important
      contributors to variable drug actions, including proarrhythmia, and are described
      here. These increasingly well-recognized examples have two important
      implications; first, it may be possible to develop drugs devoid of heretofore
      unexplained adverse effects and, second, it may become possible to preselect drug
      for individual patients based on specific genetic factors.

PMID- 14574024
TI  - Implantable diagnostic monitoring devices for evaluation of syncope, and tachy-
      and brady-arrhythmias.
AB  - Symptoms arising from cardiac arrhythmias are often transient. Consequently,
      defining the responsible rhythm disturbance remains a challenge. However, absent
      a confident diagnosis of the arrhythmic basis for the symptoms, it is not
      possible to develop an effective treatment strategy. The implantable loop
      recorder (ILR) has become a valuable element in the evaluation of patients with
      suspected intermittent arrhythmia related symptoms. In this regard, clinical
      studies have not only demonstrated its superior effectiveness compared to other
      monitoring modalities, but even suggest that it may be cost-effective for the ILR
      to be used at an earlier stage of the evaluation strategy.

PMID- 14574025
TI  - Has cardiac pacing a role in vasovagal syncope?

PMID- 14574026
TI  - Clinical trials in pacing for bradyarrhythmias.

PMID- 14574027
TI  - Cardiac resynchronization: a brief synopsis part I: patient selection and results
      from clinical trials.
AB  - Heart failure continues to affect large populations within the industrialized
      nations. Previous therapies have been directed at increasing myocardial
      contractility or decreasing vascular resistance but have not addressed the
      mechanical dysfunction within certain subpopulations with heart failure.
      Biventricular pacing has been shown to improve both acute hemodynamic parameters
      and long-term functional capacity in patients with ventricular dysynchrony and
      suffering from severe heart failure. From this data, the therapy is indicated for
      use in patients with depressed ejection fraction, bundle branch block, and either
      NYHA class III or class IV heart failure, regardless of whether or not there is a
      separate indication for ICD placement. Recent studies suggest that biventricular
      pacing may remodel the failing heart. Future studies could expand the previously
      mentioned indications to patients suffering from mild symptoms of heart failure.
      This article reviews the current demographics involved within this population,
      the acute hemodynamic benefits experienced from biventricular pacing, the long
      term function benefits experienced from the therapy, and other possible benefits
      from the therapy.

PMID- 14574028
TI  - Cardiac resynchronization: a brief synopsis part II: implant and followup
      methodology.
AB  - The following sections detail the medical approach of the three implanters within
      our group from 75 resynchronization implants as well as the technical field
      support experience from over 300 resynchronization implants.

PMID- 14574030
TI  - Pacing follow up techniques and trouble shooting during biventricular pacing.
AB  - Cardiac resynchronization has proven to be a useful adjunct therapy for heart
      failure patients with ventricular conduction disturbances. However, new issues
      have emerged including the follow-up and trouble-shooting of the biventricular
      devices. Peri-implant and immediate post-implant follow-up is necessary if
      procedure-related complications are to be revealed and proper system functioning
      ensured. Additionally, during the long-term follow-up the optimum device
      functioning should be evaluated, as should the patient's clinical and functional
      improvement. Finally, trouble-shooting resulting from the use of biventricular
      devices is another matter that needs to be addressed and physicians active in the
      field should continually upgrade their knowledge in the constantly evolving
      technologies of cardiac resynchronizers.

PMID- 14574029
TI  - Advances in devices for cardiac resynchronization in heart failure.
AB  - Patients with advanced heart failure have a high mortality and morbidity despite
      medical therapy. Depending on the underlying heart disease and severity of heart
      failure, 3.7 to 52.8% of patients have a QRS complex > or =120 ms who may have
      interventricular and intraventricular dyssynchrony correctible by cardiac
      resynchronization therapy (CRT). The latter is usually achieved with
      biventricular pacing, with the left ventricular lead placed in a tributary of the
      coronary sinus (CS), with a reported success rate between 88-92%. The technical
      advances for implantation include preformed guide sheaths to cannulate the CS,
      over the wire leads with passive fixation mechanism, and surgical placement
      methods. Device-specific CRT features include optimizing heart failure through
      insurance of a high percentage of pacing, heart failure monitoring,
      atrioventricular and interventricular timing, and avoiding double ventricular
      sensing. Furthermore, arrhythmic co-morbidities of heart failure such as atrial
      fibrillation and ventricular tachyarrhythmias can also be managed. Recent
      prospective trials suggest that there is a 30% reduction in heart failure
      hospitalization with CRT, and preliminary results suggest a survival benefit with
      CRT and implantable cardioverter defibrillator over optimal medical therapy.

PMID- 14574031
TI  - Community-based responses to impending or actual cardiac arrest and advances in
      post-cardiac arrest care.
AB  - Out-of-hospital cardiac arrest remains a major epidemiologic, clinical,
      scientific, and public health challenge. Emergency rescue systems (EMS) based in
      fire departments initially demonstrated encouraging outcomes as new strategies
      were developed in communities led by people committed to such programs, but the
      overall impact on survival has been modest. With improvement in automated
      external defibrillator (AED) technology in recent years, there has been
      increasing interest in their use by non-conventional responders in recent years.
      In parallel with the AED strategies, adjunctive strategies and therapies have
      been developed. These include the demonstration that interventions targeted to
      reperfusion of the ischemic myocardium, such as thrombolytic therapy given by EMS
      responders, clarification of the role of intravenous amiodarone for
      electrophysiologically-resistant cardiac arrest victims, and demonstration of a
      role for hypothermia in post-cardiac arrest. Thus, the range of pre-hospital and
      in-hospital strategies for improving cardiac arrest survival continues to
      broaden. The major lesson learned during the past two decades is that no single
      strategy can be relied upon to yield a major impact on the mortality from out-of
      hospital cardiac arrest. The cumulative effect of multiple strategies, working
      together toward the same goal, will ultimately provide additive effects on
      outcomes. Carefully thought out strategic approaches can maximize the effect on
      total mortality.

PMID- 14574032
TI  - Primary prevention of sudden cardiac death: trials in patients with coronary
      artery disease.
AB  - Over the past decade, four randomized, controlled trials have evaluated therapies
      for prevention of sudden cardiac death in patients with coronary disease. Three
      of the four trials have shown significant reductions in mortality with implanted
      defibrillators. Two studies failed to demonstrate any benefit from pharmacologic
      antiarrhythmic therapy. The results of these studies in similar patient
      populations have erased any doubt regarding the ability of implanted
      defibrillators to reduce the risk of sudden death in patients with coronary
      disease. Our major challenge at this time is understanding how best to utilize
      this therapy in order to bring the benefit to the maximum number of patients
      while minimizing expense.

PMID- 14574033
TI  - Rationale and patient selection for "hybrid" drug and device therapy in atrial
      and ventricular arrhythmias.
AB  - Three quite different forms of direct antiarrhythmic therapy are available for
      the treatment of cardiac arrhythmias: antiarrhythmic drugs, cardiac ablation and
      implantable devices (pacemakers and defibrillators). None of these therapies is
      fully effective and consequently they are increasingly combined. This combination
      therapy is often described as "hybrid" a term that implies fundamental different
      qualities of treatment which together provide some form of synergism. The
      mechanisms for the initiation and perpetuation of most cardiac arrhythmias are
      complex and multiple. It is therefore not surprising that single therapies are
      not completely effective. Theoretically the use of multiple different therapies
      allows more specific mechanisms of arrhythmia to be directly addressed. However,
      this is largely a theoretical concept that has only been strictly evaluated in a
      small number of studies. Studies of multiple therapies are difficult to perform
      unless the combination therapy is regarded as a strategy which can be compared to
      baseline, conventional treatment or one or more single constituent therapies from
      the combination. Despite the lack of formal studies there is a very substantial
      clinical experience which testifies to the value of hybrid therapy for the
      management of both atrial fibrillation and ventricular tachycardia/fibrillation.

PMID- 14574034
TI  - A review of clinical trials assessing the efficacy and safety of newer
      antiarrhythmic drugs in atrial fibrillation.
AB  - Clinical trials assessing the efficacy of anti- arrhythmic drugs for terminating
      atrial fibrillation have demonstrated that rate control drugs have little to no
      added efficacy compared to placebo; however, spontaneous conversion of recent
      onset atrial fibrillation is common. Antiarrhythmic drugs such as oral
      dofetilide, oral bolus-flecainide and propafenone and intravenous ibutilide all
      have a role in terminating atrial fibrillation. Active comparator trials have
      demonstrated that amiodarone is more efficacious in maintaining sinus rhythm than
      propafenone and sotalol. Multiple trials have demonstrated the safety of
      amiodarone, sotalol, dofetilide and azimilide in a post-myocardial infarction
      population and amiodarone and dofetilide in a congestive heart failure
      population. Newer antiarrhythmic agents, some with novel mechanisms of action,
      will add to the pharmacologic armamentarium in treating atrial fibrillation.

PMID- 14574035
TI  - Some recent randomized clinical trials in the management of atrial fibrillation.
AB  - It is not possible to review all the recent randomized clinical trials in
      management of atrial fibrillation. The author has chosen to select a few that
      illustrate key points. "Immediate" or "early" recurrence of atrial fibrillation
      after electrical cardioversion is an important part of inefficacy of drug therapy
      and more insight into the mechanisms of this phenomenon is needed. Two recent
      trials in which verapamil, a calcium channel blocker, and irbesartan, an
      angiotensin receptor blocking agent, added to a standard antiarrhythmic
      attenuated early recurrences of atrial fibrillation are of particular interest.
      Trials of drugs and pacing for maintenance of sinus rhythm continue to
      demonstrate only modest efficacy. Amiodarone, the most effective agent, is not
      markedly better and there are concerns about its adverse effect profile during
      long-term use. Other nonpharmacologic therapies have not yet been, but will need
      to be, evaluated in properly designed randomized clinical trials with clinically
      important end-points. The absence of a simple, highly effective treatment for the
      maintenance of sinus rhythm with few adverse effects has been part of the
      foundation for recent trials comparing the rate control strategy to the rhythm
      control strategy, particularly in the elderly patient. Six such trials have been
      completed and one is in progress. The data from these trials is quite consistent
      for the elderly patient with stroke risk factors and predominantly persistent
      atrial fibrillation: (1) any advantage for the rhythm control strategy remains
      unproven; (2) the rate control strategy has some clear advantages and should be
      considered more often as a primary approach in such patients; and (3)
      anticoagulation should not be discontinued in such high risk patients, even when
      it is felt that sinus rhythm has been maintained. Anticoagulation is under
      utilized in this setting and alternatives to warfarin are badly needed. Trials in
      progress may be helpful in this regard. Finally, primary prevention of atrial
      fibrillation needs more attention. Recent randomized trials with trandolapril
      after myocardial infarction and physiologic pacing have given some insight into
      how this might be accomplished.

PMID- 14574036
TI  - Atrial fibrillation: the role of atrial defibrillation.
AB  - Dual defibrillator implantation represents an emerging option to treat patients
      with drug refractory atrial fibrillation. Atrial antitachycardia pacing and
      cardioversion have been demonstrated to be highly effective in treating
      spontaneous tachyarrhythmias and may reduce atrial fibrillation burden by
      preventing atrial remodeling. Device implantation has been associated to improved
      quality of life and reduced hospitalization rate. Patient selection and tailored
      device programming are critical as regard to clinical outcome. Individual
      psychological profile analysis as well as underlying heart disease and atrial
      fibrillation clinical patterns represent the main drivers for the right strategy.
      Controlled studies are needed in order to define the subset of patients who can
      benefit more from device implantation.

PMID- 14574037
TI  - Hybrid therapy of atrial fibrillation: algorithms and outcome.
AB  - Rhythm control methods have not shown superior outcomes to rate control
      strategies in atrial fibrillation. Newer approaches to rhythm control employ
      "hybrid" therapies combining pharmacologic and non pharmacologic interventions.
      Pathophysiologic insights into mechanisms of atrial fibrillation (AF) suggest
      that arrhythmogenesis is due to interactions of multiple triggering rhythms and a
      complex electrophysiologic substrate resulting in the emergence of multiple
      tachyarrhythmias, often in disparate locations that may coexist in time. Thus, an
      "hybrid" therapy prescription is more likely to address several of the etiologic
      factors culminating in clinical AF. Results of pilot clinical studies of hybrid
      therapy are encouraging and involve drugs, devices and ablation techniques in
      varying permutations. Hybrid therapy algorithms using right heart procedures can
      improve efficacy with potentially lower risk. Considerations in implementation of
      these algorithms include staged or simultaneous interventions and a right versus
      left heart strategy. The parallel with the current coronary disease management
      paradigm is obvious and relevant.

PMID- 14574038
TI  - Atrial fibrillation: what are the targets for intervention?
AB  - Atrial fibrillation (AF) is a difficult and growing problem in the population.
      While medical therapy controls symptoms in many patients, a proportion of
      individuals with this common arrhythmia cannot be optimally managed with drugs
      alone. However, truly curative therapy for AF has always been one of the "holy
      grails" of electrophysiology. The surgical maze procedure was the first to offer
      permanent maintenance of sinus rhythm in patients with AF but subjected the
      patient to open heart surgery; a catheter-based translation of the maze procedure
      served as proof of concept that a catheterization technique could be used to
      treat AF. Subsequent experience has narrowed the electrophysiologist's attention
      to ablation of triggers of AF, most often residing in the pulmonary veins, rather
      than requiring more extensive ablation lines to control the arrhythmia. The
      following discussion deals with the development and current status of techniques
      for catheter ablation of atrial fibrillation, focusing on determination of
      appropriate target sites for ablation.

PMID- 14574039
TI  - A model for in vivo validation of linear lesions in the right atrium.
AB  - Linear lesions have been proposed for treatment of complex atrial arrhythmias
      including atrial macroreentry tachycardia and compartmentalization in atrial
      fibrillation. AIM: To judge the effectiveness of a given lesion design, definite
      endpoints are necessary to ascertain the completeness of the line of block
      produced. METHODS AND RESULTS: We report validation criteria for long linear
      lesions in the right atrium in 42 pts, that combine both conventional and 3D
      mapping information (CARTO). Transferring from the validation of bi-directional
      block of the cavotricuspid isthmus line for atrial flutter, we validated 2
      additional long linear lesions in the right atrium (anterior line and intercaval
      line). In addition to a complete isthmus line in all 42 pts, in 28 pts a complete
      anterior line was achieved and validated by both conventional and CARTO criteria.
      A complete intercaval line was deployed in 11 pts with complete anterior and
      isthmus lines (with a characteristic shift for the intercaval line) and in 5 pts
      without a complete anterior line (without characteristic shift). CONCLUSIONS:
      Conventional catheters placed at strategic locations on opposite sides of the
      intended ablation line, can depict a sudden characteristic change in the
      activation sequence. Using a combination of both techniques, deployment and
      validation of long linear lesion can be facilitated.

PMID- 14574040
TI  - Decremental pulmonary venous pulse propagation: impact for catheter ablation in
      focal atrial fibrillation.
AB  - BACKGROUND: Electrical isolation of pulmonary veins (PV's) is crucial to achieve
      success in catheter ablation for trigger elimination in focal atrial fibrillation
      (AF). To guide ostial PV radiofrequency (RF) delivery, it is necessary to
      identify the electrical breakthrough (EBT) between PV and left atrium. For this
      purpose, coronary sinus (CS) fixed rate pacing is commonly used. This study
      evaluated, whether CS extrastimulus pacing is superior in identifying the EBT
      area as compared to fixed rate pacing. METHODS: In 9 patients (51 +/- 10 years)
      undergoing a left sided electrophysiological study for AF ablation, 25 PV's (10
      right and 15 left-sided PV's) were mapped using a 4 French fixed-wire catheter
      with eight 6 mm coiled Platinum electrodes in a distal looped configuration
      (Revelation Helix, Cardima Inc.). For mapping and ablation the electrode loop was
      positioned in the PV ostium rectangular to the longitudinal PV axis. EBT area was
      identified as those electrodes indicating the earliest PV signals during CS
      pacing. We measured number of EBT electrodes and time between EBT and the latest
      activated bipoles at the electrode loop during fixed rate and extrastimulus
      pacing. The reduction of two or more EBT electrodes was defined as a significant
      benefit in EBT identification. RESULTS: In 22 of 25 PV's mapped PV potentials
      could be observed. Performing fixed rate pacing the EBT area was identified in a
      mean of 4.2 +/- 1 electrodes, whereas using extrastimulus pacing, EBT area could
      be significantly reduced to 2.3 +/- 0.8 electrodes. The time between EBT and
      latest electrode activated increased from 14 +/- 7 ms to 22 +/- 10 ms indicating
      an intrapulmonary conduction delay during extrastimulus pacing. In 13 of 22 PV's
      mapped (59%), extrastimulus pacing was beneficial in the identification of the
      EBT, as the primary target for RF delivery. CONCLUSIONS: CS extrastimulus pacing
      induces intra-PV decremental conduction properties allowing one to identify a
      more localised and smaller EBT area as the primary target for RF delivery.
      Performing PV ablation to treat focal AF, extrastimulus maneuvers allow to unmask
      the "true" EBT and thus may help to limit intrapulmonary RF delivery.

PMID- 14574042
TI  - Hybrid approach for minimally-invasive operative therapy of arrhythmias.
AB  - The failure of linear radiofrequency lesions to effectively replace operative
      therapy for atrial fibrillation (AF) is largely related to the inability to
      produce complete lines of conduction block. While pulmonary vein ablation enjoys
      success in patients with paroxysmal AF, patients with persistent AF and permanent
      AF fair less well. As such, a minimally-invasive, preferably "off pump"
      robotically-assisted procedure for complex arrhythmias like AF remains highly
      desirable. The shift to access from a mini-thoracotomy or port access will limit
      visualization and direct access to the ablation target. For the most part, the
      tools to overcome these limitations are not yet developed. As these develop, it
      is critical for the electrophysiologic effects of the delivered lesions to be
      assessed. With the development of non-fluoroscopic mapping systems and advances
      in imaging, a hybrid operative, electrophysiology (EP) suite can be equipped to
      provide full support for the surgeon and electrophysiologist. This will provide
      the opportunity to assess the efficacy and safety of ablation lesions, ideally
      with direct feedback to the surgeon. A hybrid approach will provide the
      opportunity to gain insights into the success and failure of specific ablation
      tools, approaches and lesions. This step will be crucial in understanding why
      specific procedures ultimately fail to cure AF and other complex arrhythmias.

PMID- 14574044
TI  - Clinical skills as demonstrated by a comprehensive clinical performance
      examination: who performs better - men or women?
AB  - PURPOSE: Determine whether gender predicted student performance on a clinical
      performance examination (CPX) when controlling for pre-matriculation and medical
      school performance. METHOD: A sixteen-station CPX, utilizing standardized
      patients (SPs), was administered to the fourth-year students three successive
      years at one United States medical school. Scores for each student by discipline
      and skills across stations were generated. Bivariate correlation and multiple
      regression analyses were performed to determine relationships between students'
      scores and pre-matriculation information (age, gender, MCAT, and undergraduate
      GPA) and medical school performance (first-, second- and third-year GPA, and
      USMLE Step 1). RESULTS: The CPX mean score for all students was 65.1% (SD 6.2).
      The mean total score for men (n = 182) and women (n = 93) was 64.0% and 67.0%,
      respectively. Being a woman, positively affected a student's score in two models
      controlling for pre-matriculation and medical school performance by 2.8% or 0.47
      standard deviations (SD) and 2.3% or 0.39 SD, respectively. Women scored
      numerically higher than men in all seven disciplines (internal medicine,
      obstetrics/gynecology, pediatrics and psychiatry, p < 0.05) and for nine skills
      across all stations (introduction, history, physical examination, counseling and
      interpersonal, p < 0.05). CONCLUSION: Women performed better than men on the
      University of Kentucky CPX. Being a woman was a positive and independent
      predictor of performance.

PMID- 14574041
TI  - Clinical results with catheter ablation: AV junction, atrial fibrillation and
      ventricular tachycardia.
AB  - With the limitations of pharmacologic and device therapies for atrial
      fibrillation and ventricular tachycardia, catheter ablation is assuming a larger
      role in the management of patients with these common arrhythmias. Multiple case
      series and clinical trials have helped to define the evolving role of these
      techniques for ablation of the atrioventricular node, atrial fibrillation, and
      ischemic ventricular tachycardia. Based on very low complication rates, excellent
      efficacy and proven outcomes with radiofrequency ablation of the atrioventricular
      node, this approach with permanent pacing should play a larger role in the
      treatment of symptomatic patients with permanent atrial fibrillation. While
      linear ablation of atrial fibrillation has limited clinical utility for the
      treatment of this common arrhythmia, the results of multiple case series of focal
      atrial fibrillation ablation indicate the potential for an expanding role of this
      curative technique. Catheter ablation techniques for ventricular tachycardia in
      the setting of coronary artery disease have a role as supplemental therapy to the
      implantable cardioverter defibrillator in patients with recurrent
      pharmacologically refractory ventricular arrhythmias requiring frequent device
      interventions.

PMID- 14574043
TI  - Catheter ablation to suppress atrial fibrillation: evolution of technique at a
      single center.
AB  - BACKGROUND: Catheter ablation of atrial fibrillation is a rapidly evolving art.
      There is currently no consensus as to optimal methodology. We report a sequential
      experience, during which three distinct ablation techniques were utilized.
      METHODS: A cohort of 112 patients in whom atrial fibrillation onset was
      precipitated by ectopy arising solely from myocardium investing the pulmonary
      veins underwent catheter ablation using one of three techniques: focal (Group A);
      individual vein encircling (Group B); vestibule encircling (Group C). In each
      group, non-fluoroscopic guidance of the mapping and ablation process was provided
      by the tandem use of CARTO and intracardiac echocardiography. RESULTS: In all
      groups, endocardial topography was complex, and ablation electrode-endocardial
      contact was often unstable. Maximal electrode temperatures were low, despite
      frequent echocardiographic evidence of myocardial boiling. A significant
      progression in the number of radiofrequency energy applications between groups A
      and C was observed. Although acute suppression of atrial fibrillation
      inducibility was observed uniformly, chronic suppression rates were significantly
      different: Group A = 47%; Group B; 69%; Group C = 87%. CONCLUSIONS: In this non
      concurrent cohort, the rate of chronic suppression of atrial fibrillation
      correlated with the amount of myocardium ablated or electrically isolated.
      Prospective data will be required to further evaluate whether "more is better."

PMID- 14574045
TI  - The importance of active involvement in learning: a qualitative study on learning
      results and learning processes in different traineeships.
AB  - INTRODUCTION: In order to gain more insight into learning in different
      traineeships we sought students' opinions on their experiences. METHOD: 24
      students of Maastricht University, the Netherlands, were interviewed: 8 medical
      students, and 16 students in the mental health science programme of the Faculty
      of Health Sciences (8 research trainees (MHS-res.) and 8 trainees in mental
      health care practice (MHS-prac.). Students' perceptions about instructive,
      difficult and less instructive learning experiences were recorded on audiotape.
      The literal transcripts of the interviews were analysed and categorised. RESULTS:
      The most frequently mentioned learning process was "learning by doing" followed
      by "actively overcoming gaps in knowledge and skills". These processes occurred
      with instructive and difficult experiences. Other processes were "learning by
      seeing things in practice" and "preparation and evaluation". Learning outcomes
      were categorised as learning about: working, professional competences and
      personal growth. Most frequently mentioned - in most cases with difficult
      experiences - were "professional knowledge and skills", "learning about personal
      growth" and "learning about working". The latter was mentioned most often by MHS
      res. students. Medical students' responses suggested that they occasionally
      perceived the clerkship environment as stressful. DISCUSSION AND CONCLUSIONS:
      Although the small sample size precludes any firm conclusions, the overwhelming
      impression is that students prefer being actively involved in their learning
      process. In addition, traineeships appear to introduce students to professional
      working life the hard way. Investigating how teachers and supervisors can
      stimulate active learning and facilitate the introduction to professional
      practice might be subjects for fruitful further investigation.

PMID- 14574046
TI  - A strategy to standardize the learning of core clerkship objectives.
AB  - BACKGROUND: Consistent and effective implementation of clinical clerkship
      objectives remains elusive. Using the behavioral principles of self assessment,
      active learning and learner differences, we designed an objectives checklist to
      ensure that all students mastered a core body of internal medicine (IM) knowledge
      and to facilitate self-directed learning. METHODS: We developed a 54-item
      learning objectives checklist card in the IM clerkship. In a randomized
      controlled trial by clerkship site and block, students in the intervention group
      received the checklist card and were instructed to obtain sign off on objectives
      by faculty and housestaff and to seek teaching, literature, and clinical
      experiences to satisfy objectives unmet through routine activities. Intervention
      group faculty and housestaff were oriented to the use of the checklist. Both
      intervention and control groups received the course syllabus. We assessed
      learning with faculty and housestaff evaluations, student knowledge self
      assessment, and a written examination. Satisfaction with the cards was assessed
      with written evaluations. RESULTS: There were no significant differences in ward
      evaluations, examination scores or self-assessed knowledge between students using
      the learning objectives cards and control groups. Faculty were more likely than
      students to agree that objectives cards improved education. CONCLUSIONS: An
      intervention designed to guide students in the use of a learning objectives card
      did not enhance learning as assessed by ward evaluations, a written examination,
      and satisfaction surveys. It is possible that more sensitive outcome measures
      could detect differences in knowledge for students using learning objectives
      checklist cards.

PMID- 14574047
TI  - A sequenced OSCE for licensure: administrative issues, results and myths.
AB  - In response to stakeholder demands for a more cost-effective clinical
      examination, the Medical Council of Canada adopted a sequenced format for the
      OSCE component of its licensure examination. The sequenced OSCE was administered
      in 1997 at 14 sites and assessed 1,796 test takers. The 10-station screening test
      had an alpha = 0.66 (M = 61.3%, SD = 4.7%). The fail rate of 1.7% for Canadian
      first-time takers was the lowest since 1992. Significant savings were realized
      despite costs incurred by the new format. The logistical problems that were
      encountered were largely due to the constraints of administering a multi-site
      OSCE. Although the sequenced format was cost effective and psychometrically
      acceptable, the response of many test takers and faculty members was negative.
      Consequently, it is the logistical and political lessons that may be the most
      generalizable.

PMID- 14574048
TI  - The use of standardized patients to teach and test interpersonal and
      communication skills with students in speech-language pathology.
AB  - The purpose of this study was to investigate the use of standardized patients
      (SPs) with aphasia to teach interpersonal and communication skills to new
      graduate student-clinicians in Speech-Language Pathology, and to test those
      skills via serial Objective Structured Clinical Examinations (OSCEs). This study
      had three phases: (1) clinical teaching using SPs, (2) mid-term evaluation via a
      single case OSCE, and (3) end-of-term evaluation via a multi-case OSCE. These
      phases were integrated with classroom teaching and testing components over a 16
      week academic semester. Eighteen students participated while concurrently
      enrolled in a course on diagnosis and management of aphasia taught by the first
      author. One half of the class received initial instruction via a combination of
      didactic lecture and standardized patient interaction, while the other half of
      the class was taught initially via didactic lecture only. On OSCE I, there was no
      statistically significant difference between the two groups in their
      interpersonal and communication skills, with the class as a whole demonstrating
      less than acceptable competency. After targeting these skills in all students via
      additional class lectures, there was a statistically and clinically significant
      improvement in their competency in this area on OSCE II. Student feedback was
      positive.

PMID- 14574049
TI  - Effects of problem-based learning curricula on faculty learning: new lenses, new
      questions.
AB  - Literature on the impact of problem-based learning (PBL) in medical education has
      short-changed important questions about the effect of PBL curricula on faculty
      learning and on faculty knowledge of their subject matter. This paper opens up
      new questions about the impact of PBL in medical colleges and other health
      sciences by focusing attention on its effects on faculty learning, on collegial
      networks in medical colleges, and, consequently, on other scholarly work by
      faculty. A brief review of research on the effects of PBL on faculty and faculty
      development is followed by a synthesis of relevant research findings from
      research on teaching and faculty learning in other disciplines. A new conceptual
      framework, drawn from the educational paradigms, methods and empirical findings
      from those other areas of higher education research and research on secondary
      school teaching, is applied to designing, examining, and evaluating problem-based
      learning. Viewing faculty as learners prompts a new research agenda including
      questions such as: What do faculty members learn by participating in integrative,
      interdisciplinary problem-based learning courses? How? How is that learning
      related to or integrated with other aspects of their scholarly work?

PMID- 14574050
TI  - B-type natriuretic peptide: physiologic role and assay characteristics.
AB  - The discovery of cardiac natriuretic peptides two decades ago has lead to
      considerable research to investigate their biochemical and physiological
      properties. Clearly the heart is not just a pump but is also an endocrine organ
      that together with the kidneys control volume overload. The natriuretic peptides
      are a group of structurally similar but genetically distinct peptides that
      exhibit diverse actions in cardiovascular, renal, and endocrine homeostasis.
      Atrial natriuretic peptide (ANP) and brain (or B-type) natriuretic peptide (BNP)
      are of myocardial cell origin. BNP is released mainly from the left ventricle in
      response to volume overload and has become the first biochemical marker for the
      identification of individuals with congestive heart failure (CHF). The
      development of assays, including rapid point-of-care tests, has made BNP
      measurement a clinical reality.

PMID- 14574051
TI  - B-type natriuretic peptide: spectrum of application. Nesiritide (recombinant BNP)
      for heart failure.
AB  - The therapeutic goals for patients hospitalized with acutely decompensated heart
      failure are to reverse acute hemodynamic abnormalities, relieve symptoms, and to
      initiate heart failure therapies which will decrease disease progression and
      improve long-term survival. Nesiritide (recombinant B-type natriuretic peptide)
      is the first in a new class of therapeutic agents for the treatment of heart
      failure and has been demonstrated to offer a unique combination of safety and
      efficacy. The use of nesiritide on top of standard care including diuretic
      therapy, has been proven to lead to meaningful clinical benefits in a broad range
      of acutely decompensated heart failure patients. Nesiritide is an attractive
      therapeutic option because of its more rapid and sustained hemodynamic profile,
      more favorable effects on neurohormonal suppression, with less adverse effects
      than alternative intravenous heart failure treatments such as nitroglycerine,
      nitroprusside, dobutamine, or milrinone. The use of nesiritide is the most
      effective initial treatment approach among currently available strategies to
      reverse acutely decompensated heart failure and to facilitate optimization of the
      heart failure medical regimen.

PMID- 14574052
TI  - The diagnosis of acute congestive heart failure: role of BNP measurements.
AB  - For the acutely ill patient presenting to the emergency department with dyspnea,
      an incorrect diagnosis could place the patient at risk for both morbidity and
      mortality. The stimulus for BNP release is a change in left-ventricular wall
      stretch and volume overload. A rapid whole blood BNP assay has recently approved
      by the FDA (Triage BNP Test, Biosite Inc, San Diego CA) that allows one to
      quickly evaluate the dyspneic patient, and set the stage for the recently
      completed multinational Breathing Not Properly (BNP) study. The Breathing Not
      Properly Multinational Study was a seven center, prospective study of 1586
      patients who presented to the emergency department with acute dyspnea and had BNP
      measured with a point-of-care assay upon arrival. BNP was accurate in making the
      diagnosis of CHF and correlated to severity of disease. It could have reduced
      clinical indecision by 74%. Algorithms are being developed for use in the
      emergency room which takes into account other illnesses that might raise BNP
      levels. BNP levels should be extremely important in ruling out and diagnosing
      decompensated CHF, as long as baseline "euvolemic" BNP values are known. Finally,
      it is possible that use of BNP levels might not only be helpful in assessing
      whether or not a dyspneic patient has heart failure, but it my turn out to be
      useful in making both triage and management decisions.

PMID- 14574053
TI  - Acute Emergency Department management of heart failure.
AB  - The Emergency Department (ED) is a common location for acutely decompensated
      Heart Failure (HF) patients to seek care. Consequently, there is the opportunity
      for significant clinical benefits when care is managed appropriately. This
      article reviews the importance of an accurate diagnosis, the necessity to search
      for underlying precipitants of the HF decompensation, and the impact of early
      treatment on the subsequent length of hospitalization. It also discusses the
      value of the ED observation unit for short intensive management of HF, the
      potential financial benefits of this strategy, and the ability of nesiritide to
      decrease future revisits when used in this environment.

PMID- 14574054
TI  - Use of BNP levels in monitoring hospitalized heart failure patients with heart
      failure.

PMID- 14574055
TI  - Outpatient management of heart failure.
AB  - With the increasing prevalence of heart failure, the greater spectrum of proven
      therapies, the broader spectrum of cardiac dysfunction qualifying for treatment
      and the recognition that heart failure is difficult to diagnose, the need for an
      indicator of both the diagnosis and the efficacy of treatment in this condition
      is clear. Plasma concentrations of the B-type natriuretic peptides are related to
      cardiac function and cardiovascular prognosis. They parallel hemodynamic
      indicators of cardiac dysfunction and may therefore act as indicators of the
      adequacy of therapy. In the one published trial of outpatient treatment of heart
      failure guided by plasma BNP, 69 patients (LVEF < 40%, NYHA II-IV) were
      randomised to treatment according to plasma peptide levels or a clinical score.
      The primary end point of total cardiovascular events was reduced in BNP-guided
      patients (19 versus 54 events) with p < 0.001 in a multivariate analysis. The
      natriuretic peptides and particularly plasma BNP and aminoterminal proBNP
      promised to provide an objective guide for optimising treatment in heart failure.

PMID- 14574057
TI  - B-type natriuretic peptide and renal disease.
AB  - B-type natriuretic peptide (BNP) is a cardiac neurohormone which has a principal
      effect on the kidney to signal both natriuresis and diuresis. Both BNP and renal
      function are prognostic indicators of survival in patients with congestive heart
      failure (CHF). However, the relationships between BNP, renal function, and CHF as
      an emergency diagnosis, are not completely understood. The correlation between
      BNP and estimated glomerular filtration rate (eGFR) is approximately r = -0.20.
      At an eGFR < 60 ml/min/1.73 m2, the optimum cutpoint for BNP to diagnose CHF
      rises to approximately 200 pg/ml. At this cutpoint the area under the receiver
      operating characteristic curve is 0.81, indicating that BNP is of diagnostic
      value in this group. Importantly, the precursor molecule N-terminal proBNP has a
      stronger correlation with eGFR of approximately -0.60, and is influenced by the
      age-related decline in renal function above the lower bounds of normal of < 60
      ml/min/1.73 m2. Because BNP is a principal messenger from the heart to the
      kidneys, and because it is influenced by renal filtering function, parenchymal
      mass, and tubular function, BNP can be leveraged in assisting in the diagnosis
      and management of combined heart and renal failure.

PMID- 14574056
TI  - The role of brain natriuretic peptide in population screening.
AB  - While measurement of plasma BNP concentration has been shown to be useful in the
      diagnosis of heart failure, its role as a screening test for detection of pre
      clinical ventricular remodeling or dysfunction in the general population has not
      been established. Here we review available population-based studies assessing the
      predictive characteristics of BNP for the detection of pre-clinical structural
      heart disease (Stage B Heart Failure).

PMID- 14574058
TI  - B-type natriuretic peptide in heart transplantation: an important marker of
      allograft performance.
AB  - The successful management of a cardiac allograft recipient centers around
      detection of allograft dysfunction early and preferably in a noninvasive manner.
      Up to this point, echocardiography or right heart catherization with
      endomyocardial biopsy are the only definitive methods available to diagnose
      allograft dysfunction. However, these methods do not reflect early structural
      changes and neurohormonal aberrations involved in allograft dysfunction. B-type
      natriuretic peptide (BNP) reflects ventricular wall stress and pressure and early
      studies have intimated potential usefulness of this marker in heart
      transplantation. Recent studies utilizing point-of-care BNP assay in heart
      transplant recipients have demonstrated elevated BNP levels at baseline compared
      with controls. Furthermore, the two most significant correlates of BNP levels are
      central hemodynamic perturbations despite preserved systolic function and
      presence of right sided cardiac dysfunction. Initial investigations have
      demonstrated BNP levels to serve as prognostic marker for cardiac related events
      and to track responses to therapeutic interventions. Further studies are needed
      to further assess the utility of BNP as surrogate marker for cardiac function and
      adaptation.

PMID- 14574059
TI  - Natriuretic peptide hormone measurement in acute coronary syndromes.
AB  - Cardiac Ischemia is an important trigger for the release of B-type natriuretic
      peptide (BNP). BNP and N-terminal pro-BNP (N-proBNP) are emerging as important
      biomarkers for risk stratification in patients with acute coronary syndromes.
      Higher levels of BNP and pro-BNP are associated with a greater risk for death and
      heart failure, independent of traditional clinical variables and levels of other
      biomarkers such as troponins and C-reactive protein. The therapeutic implications
      of these findings are not yet known.

PMID- 14574061
TI  - Fas-beyond death: a regenerative role for Fas in the nervous system.
AB  - Fas (CD95, APO-1), a member of the TNF superfamily, is a prototypical "death
      receptor" which transduces apoptotic signals in a variety of cell types. However,
      cell death is not the only possible outcome of Fas signalling. Fas engagement by
      Fas Ligand can also trigger proliferation or differentiation, promote tumour
      progression and angiogenesis, and induce cytokine secretion and integrin
      expression. Recently, we have reported that Fas engagement induces a potent
      regenerative response in sensory neurons in vitro, and enhances peripheral nerve
      regeneration in vivo. In contrast, other types of neurons, notably motoneurons,
      are acutely sensitive to Fas-induced apoptosis. Here, we review the literature on
      non-apoptotic Fas signalling pathways, and discuss the potential roles, molecular
      mechanisms, and regulators of Fas signalling in the nervous system.

PMID- 14574060
TI  - Practical considerations for BNP use.
AB  - The evolving paradigm of heart failure has now been expanded to include the
      favorable neurohormonal, structural and hemodynamic profile of B-type natriuretic
      peptide [BNP]. As a marker of left ventricular dysfunction, BNP is a practical
      tool that facilitates diagnosis, contributes to prognostic evaluations and tracks
      disease severity. BNP elevations vary according to gender, disease states and
      perhaps obesity but in general elevated levels are consistent not only with left
      ventricular stress but likely represent the best surrogate for ongoing left
      ventricular remodeling. The full utility of BNP surveys has not yet been realized
      but emerging areas of use include clinical assessment by physician extenders,
      post-MI assessment, and a target of tailored therapy for heart failure. New
      biomarkers for heart failure similar to BNP are on the horizon but their clinical
      niche has yet to be determined.

PMID- 14574062
TI  - Measurement of CTL-induced cytotoxicity: the caspase 3 assay.
AB  - Cytotoxic T lymphocytes (CTL) are critical effector cells of the immune system.
      Measurement of target cell damage has historically been an important measure of
      CTL function. CTL kill their target cells predominantly by inducing programmed
      cell death, or apoptosis. The gold standard for CTL-mediated cytotoxicity has
      been the (51)Cr release assay. However, measurement of target cell lysis by
      (51)Cr release does not provide mechanistic information on the fate of target
      cells, especially at the single cell level. Given the recent advances in our
      understanding of programmed cell death, newer assays are required which evaluate
      the status of the apoptotic pathways in target cells. We have developed a flow
      cytometry-based assay for CTL-mediated cytotoxicity based on specific binding of
      antibody to activated caspase 3 in target cells. Our assay is convenient and more
      sensitive than the (51)Cr release assay. The use of this assay should allow
      mechanistic studies of the intracellular events resulting from CTL attack.

PMID- 14574063
TI  - Satellite cell depletion in degenerative skeletal muscle.
AB  - Adult skeletal muscle has the striking ability to repair and regenerate itself
      after injury. This would not be possible without satellite cells, a subpopulation
      of cells existing at the margin of the myofiber. Under most conditions, satellite
      cells are quiescent, but they are activated in response to trauma, enabling them
      to guide skeletal muscle regeneration. In degenerative skeletal muscle states,
      including motor nerve denervation, advanced age, atrophy secondary to
      deconditioning or immobilization, and Duchenne muscular dystrophy, satellite cell
      numbers and proliferative potential significantly decrease, contributing to a
      diminution of skeletal muscle's regenerative capacity and contractility. This
      review will highlight the fate of satellite cells in several degenerative
      conditions involving skeletal muscle, and will attempt to gauge the relative
      contributions of apoptosis, senescence, impaired proliferative potential, and
      host factors to satellite cell dysfunction.

PMID- 14574064
TI  - Defects in cAMP-pathway may initiate carcinogenesis in dividing nerve cells: a
      review.
AB  - The mechanisms of carcinogenesis in nervous tissues are not well understood. It
      is now established that adenosine 3,',5'-cyclic monophosphate (cAMP)-pathway
      plays a crucial role in initiating differentiation in transformed and embryonic
      cells of neuronal and glial origin. Therefore, we propose that defects in the
      cAMP-pathway may initiate the first phase of carcinogenesis (immortalization).
      Subsequent genetic abnormalities in oncogenes, anti-oncogenes or other cellular
      genes individually or in combination may lead to transformation (cancer
      phenotype). This hypothesis is derived from the fact that an elevation of the
      cAMP level in murine NB cells induces terminal differentiation in many of these
      cells in spite of the fact that they are highly aneuploid. Additional changes in
      cAMP-regulated genes responsible for initiating differentiation may make these
      cells resistant to cAMP or may make the cAMP-effect on differentiation
      reversible. Indeed, cAMP-resistant cells exist in NB cell populations, and the
      cAMP-effect on differentiation is reversible in glioma cells. Identification of
      genes that initiate, promote and maintain terminal differentiation and those
      which prevent differentiation following elevation of cAMP in NB cells may
      increase our understanding of the mechanisms of carcinogenesis. This review
      illustrates the following: (a) historical background leading to the discovery of
      cAMP as an inducer of differentiation in nerve cells; (b) identification of
      potential sites in cAMP-pathway that may play a crucial role in initiating the
      first phase of carcinogenesis (immortalization) and potential gene targets in
      immortalized cells whose alterations may cause neoplastic transformation of nerve
      cells. It is interesting to note that the cAMP pathway remains responsive to an
      elevated cAMP level in inducing differentiation in NB cells in spite of
      chromosomal anomalies and genetic changes associated with the maintenance of a
      cancer phenotype.

PMID- 14574065
TI  - Health care services and Pap testing behavior for Chinese women in British
      Columbia.
AB  - The health care services and sociodemographic profiles of Chinese women residing
      in each of five neighborhoods of Vancouver and Richmond, British Columbia, were
      examined and compared to Pap testing rates. Information was collected from the
      provincial medical directory, the cervical cancer screening program, and a
      community-based survey. A total of 159 Chinese primary care physicians, 3 Chinese
      gynecologists, and 9 health clinics were identified within these neighborhoods
      and 769 Chinese women responded to the survey. Significant differences were found
      between neighborhoods in Pap testing rates, with Chinatown having the lowest
      rates. Differences between neighborhoods were also found in the availability of
      Chinese language health care services, sociodemographic profiles of the Chinese
      population, individual preferences and experiences with health care services,
      which were also related to Pap testing rates. The implications of these findings
      upon the planning of effective health care services within local neighborhoods
      are discussed.

PMID- 14574066
TI  - "I have no time for potential troubles": Russian immigrant women and breast
      cancer screening in Israel.
AB  - The author's earlier study of Russian immigrant women's attitudes and practices
      related to the early detection of cancer has shown their low participation in
      breast screening activities, from BSE to mammography. Most respondents were
      educated women who acknowledged their personal risk, understood the role of
      screening, but still avoided preventive action. In this qualitative research, the
      gap between cognitions and behavior is explored further by means of in-depth
      interviews and focus groups with 34 women aged 50-74 who moved to Israel after
      1990. All Israeli women of this age are entitled for screening mammography free
      of charge once every 2 years. The findings point to a low place of preventive
      health concerns in the personal agenda of female immigrants, loaded by the more
      immediate survival needs (income, housing, support of other family members,
      etc.). Other barriers include the lack of referral from primary care providers,
      fear of cancer diagnosis, apprehensions of irradiation and pain involved in
      mammography, fatalist general attitude towards health and illness, and mistrust
      of current cancer therapy. Many older women (60+), whose risks are actually
      higher, shared a false belief that breast cancer strikes younger women and they
      are already past the age of concern. Older informants avoided gynecological
      clinics because of male gender of most gynecologists, their poor command of
      Hebrew, and a belief that gynecological checkups are irrelevant and even shameful
      in their age. It is concluded that female immigrants, especially older ones, must
      be a special target group for preventive health interventions.

PMID- 14574067
TI  - Identifying best practices of community participation in providing services to
      refugee survivors of torture: a case description.
AB  - There is an increased interest in best practices in the design and implementation
      of specialized programs for refugee survivors of torture. The processes taking
      place in the development of such a program also warrant assessment. In
      particular, this paper addresses the importance of community participation. Using
      the Host Support Program for Survivors of Torture as a case study, we identify
      the community participation practices that emerged during stages of program
      development and describe how these practices have made possible a collaborative
      service delivery model and facilitated community capacity building that addresses
      the complex needs of refugee survivors of torture. The process of community
      collaboration is discussed as central to the process of effective community
      participation and organizing. The illustrated benefits of community participation
      position this model as a best practice.

PMID- 14574068
TI  - Iranian migrants' discourses of health and the implications for using
      standardized health measures with minority groups.
AB  - This paper explores the concept of health implied in the SF-36 within a group of
      Iranians in Australia. Qualitative data were collected from a sample of 21 people
      -10 females and 11 males. For the first time, the NUD*IST program was used to
      organize and manage the data in Persian (also known as Farsi), the language
      spoken by Iranians. Health was defined in terms of holistic, spiritual, social,
      physical/emotional aspects, and absence-of-disorder dimensions. Among these,
      physical, absence of disorder, holistic, and spiritual aspects of health were
      mentioned more frequently than other themes. The findings of the study raise
      concerns about the extent to which the SF-36 captures the diversity of the
      concept of health as expressed by the sample of Iranian migrants.

PMID- 14574069
TI  - Employment frustration and alcohol abuse/dependence among labor migrants in
      California.
AB  - We test whether or not labor market frustration is associated with clinical
      alcohol abuse/dependence diagnoses among labor migrants living in California. Our
      sample consists of 1576 Mexican labor migrants in Fresno, CA, who migrated for
      the purpose of seeking employment. Using clinical criterion (DSM-III-R), we find
      that frustrating experiences resulting from labor market exclusion and
      discrimination are significantly related to past-year alcohol abuse/dependence.
      Similarly, although high levels of social support are salutary, they are not
      protective among those who experience moderate/high levels of employment
      frustration. Since Mexican-origin immigrants have low rates of health insurance
      coverage and lower propensities for formal help-seeking, community outreach
      programs that target labor migrants are essential to this population's mental
      health maintenance.

PMID- 14574070
TI  - Factor Xa-A pleuripotential protease.

PMID- 14574071
TI  - The impact of heparin compounds on cellular inflammatory responses: a construct
      for future investigation and pharmaceutical development.
AB  - Atherosclerotic disease is recognized as a chronic inflammatory disorder with
      intermittent and widely variable phases of cellular proliferation and heightened
      thrombotic activity. The multi-tiered links between inflammation, atherogenesis
      and thrombogenesis provide a unique opportunity for research and development of
      pharmaceuticals which target one or more critical pathobiologic steps (Fig. 1).
      The purpose of the following review on heparin compounds is to comprehensively
      examine the multi-cellular, pleuripotential effects of a commonly used
      anticoagulant drug in the context of normal and disease-altered vascular
      responses and illustrate possible constructs for avenues of subsequent
      investigation in the field of atherothrombosis. The overview is divided into five
      integrated parts; antiinflammatory properties of the normal vessel wall, the
      relationship between glycosaminoglycans and inflammation, heparin-mediated
      effects on cellular inflammatory responses, association between molecular weight
      and antiinflammatory capabilities, and oral heparin compounds for achieving
      prolonged cell-based inhibition.

PMID- 14574072
TI  - Plasmin-mediated proteolysis of vascular endothelial cell heparin releasable
      tissue factor pathway inhibitor.
AB  - BACKGROUND: Fibrinolytic therapy represents a widely available and effective
      treatment modality for ST segment elevation myocardial infarction (MI). Its
      overall benefit is attenuated by a high incidence of coronary arterial
      reocclusion. METHODS/RESULTS: Human umbilical vein endothelial cells (HUVEC) were
      incubated with unfractionated heparin (1.5 U/ml) (to provoke tissue factor
      pathway inhibitor [TFPI] release) followed by the addition of varying
      concentrations of alteplase (recombinant tissue plasminogen activator),
      plasminogen, their combination or plasmin alone. In the presence of 20% TFPI
      depleted human plasma, there was a concentration-dependent decrease in TFPI
      levels following incubation with alteplase (28% reduction at 200 ng/ml; P <
      0.01); 37% reduction at 1000 ng/ml (P < 0.001). Similar effects were observed for
      alteplase combined with plasminogen (P < 0.001), plasmin alone (P < 0.001) and
      with HUVEC incubated with low concentrations of plasmin (10 ng/ml) prior to
      heparin exposure. CONCLUSIONS: Plasmin, a non-specific protease, degrades
      vascular endothelial cell (constitutive) TFPI and heparin-releasable TFPI,
      attenuating an important pathway of vascular surface thromboresistance and
      potentially contributing to coronary arterial reocclusion after fibrinolytic
      therapy.

PMID- 14574073
TI  - Increase in interleukin-6 in the first hour after coronary stenting: an early
      marker of the inflammatory response.
AB  - BACKGROUND: Inflammation after coronary stenting presages adverse outcomes after
      percutaneous coronary intervention (PCI). While changes in inflammatory markers
      have been defined 24-72 hours after PCI, potential changes during the first few
      hours have not. This study was designed to determine if a systemic inflammatory
      response could be measured within the first hour after stenting. METHODS:
      Patients (n = 25) undergoing coronary stenting, with predominantly (n = 23) acute
      coronary syndromes were enrolled prospectively in this registry. Blood samples
      were collected before PCI, and 10 minutes, 1 hour and 18-24 hours later. No
      patient received a glycoprotein IIb-IIIa inhibitor. Concentrations of C-reactive
      protein (CRP), interleukin-6 (IL-6), and interleukin-1 receptor antagonist (IL
      1Ra) and soluble CD40 ligand (sCD40L) were measured using ELISA. RESULTS: CRP and
      sCD40L did not change in the first hour after stenting. By contrast, IL-6
      increased in the first hour (before = 7.6 +/- 7.7 pg/ml, 1 hour = 12 +/- 12
      pg/ml; p < 0.001). The concentration of IL-1Ra tended to be greater after 1 hour
      (before = 426 +/- 261 pg/ml, 1 hour = 511 +/- 406 pg/ml; p = 0.11). Increase in
      IL-1Ra was apparent only in female subjects (p = 0.004 for the difference in
      trend between the two genders). A correlation was not observed between the
      increase in IL-6 at 1 hour and the increase in CRP at 24 hours (r = -0.21).
      CONCLUSIONS: In patients undergoing coronary stenting, increase in IL-6 can be
      detected 1 hour after PCI, and thus IL-6 may be an early initiator of the
      systemic inflammatory response to stenting.

PMID- 14574074
TI  - Relationship between minor myocardial damage and inflammatory acute-phase
      reaction in acute coronary syndromes.
AB  - BACKGROUND: In severe acute coronary syndromes (ACS) elevation of markers of
      inflammation and acute phase reaction (APR) like C-reactive protein (CRP) as well
      as a release of troponin have been reported. Using a high sensitivity troponin T
      (TnT) test we investigated whether an APR occurs in ACS only in the presence of
      ischemic myocardial damage. METHODS: In 85 patients with ACS C-reactive protein
      (CRP), serum amyloid A (SAA), fibrinogen, thrombin antithrombin III complexes
      (TAT) and kallikrein were determined vs. high sensitive TnT (> or =0.02 ng/ml)
      initially and 2 d later vs. 45 patients with stable angina pectoris and 42
      controls. RESULTS: In stable angina pectoris, markers of inflammation and
      coagulation were slightly elevated (p < 0.05). Initially in ACS elevations of CRP
      to 1.2 +/- 0.3 mg/dl, SAA to 4.8 +/- 2.6 mg/dl and fibrinogen to 448 +/- 21 mg/dl
      (all p < 0.01 vs. controls) were found followed by a significant APR (p < 0.01).
      In the subgroup of TnT positive ACS patients, an APR with increased CRP (4.1 +/-
      1.3 mg/dl), SAA (20.4 +/- 8.3 mg/dl), and fibrinogen (641 +/- 45 mg/dl) was
      detectable (all p < 0.05 vs. TnT negative patients). In contrast, patients
      without TnT release showed APR markers comparable to patients with stable angina
      pectoris. CONCLUSION: Our findings demonstrate an association between myocardial
      injury in ACS and acute phase reaction as evidenced by several molecular markers.
      A highly sensitive TnT-test identified myocardial injury in about all patients
      with APR while a standard TnT cut-off (0.1 ng/ml) missed 32% of these patients.
      Thus, the APR in patients with ACS is strongly associated with at least minor
      ischemic myocardial damage and prior findings of an APR independent from
      myocardial injury are probably based on less sensitive troponin tests.

PMID- 14574075
TI  - Factor V Leiden and risk of ischemic stroke in nonvalvular atrial fibrillation:
      the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study.
AB  - BACKGROUND: Atrial fibrillation is a major cause of cardioembolic stroke. Since
      atrial and venous pressures are similar, genetic variants that promote venous
      thromboembolism may increase the risk of atrial thrombi and subsequent stroke in
      atrial fibrillation. METHODS: We conducted a nested case-control study of the
      association between the presence of factor V Leiden polymorphism and incident
      ischemic stroke within a prospective cohort of 13,559 adult patients with
      diagnosed nonvalvular atrial fibrillation between July 1, 1996 and December 31,
      1997. Incident cases with ischemic strokes were identified through August 31,
      1999 and matching stroke-free controls were enrolled. RESULTS: One hundred thirty
      seven case patients with incident stroke and 214 controls were enrolled. Cases
      were older, more likely to be women, and more likely to have a prior stroke,
      heart failure, hypertension, diabetes, and coronary disease. The factor V Leiden
      polymorphism was present in 5.8% of cases and 3.7% of controls (P = 0.36). Among
      non-anticoagulated patients, 7/96 (7.3%) case patients and 3/81 (3.6%) control
      subjects were heterozygous for factor V Leiden (Odds Ratio 2.1 [95% CI: 0.5
      8.4]). Adjustment for known stroke risk factors did not significantly change the
      observed association in non-anticoagulated patients (adjusted OR 1.9 [0.5-8.0]).
      CONCLUSIONS: Within a large nested case-control sample of patients with atrial
      fibrillation, factor V Leiden was not significantly associated with risk of
      stroke. However, given the suggestive nature of our findings, further study in
      even larger numbers of patients is needed to clarify the impact of factor V
      Leiden on stroke risk in atrial fibrillation.

PMID- 14574076
TI  - Clinician update: direct thrombin inhibitors in acute coronary syndromes.
AB  - Antithrombotic therapy has become the cornerstone of the treatment for
      atherosclerotic cardiovascular disease. Unfractionated heparin (UFH) has been the
      thrombin inhibitor of choice for decades. UFH, however, has its deficiencies. To
      overcome these problems several direct thrombin inhibitors (DTIs) have been
      developed. These agents are capable of inactivating clot-bound thrombin more
      efficiently, and provide more predictable and safer anticoagulation in patients
      with of acute coronary syndromes (ACS). The initial studies of hirudin and
      bivalirudin in the clinical settings of acute myocardial infarction (AMI),
      unstable angina (UA) and percutaneous coronary interventions (PCI) conducted in
      the early 1990s proved to be disappointing. As the knowledge of more appropriate
      use of these drugs progressed, there is a renewed interest in DTIs. Herein we
      will review the clinical studies assessing hirudin, bivalirudin and argatroban in
      the settings of AMI, UA and PCI.

PMID- 14574077
TI  - Complete lysis of left ventricular giant thrombus with fibrinolytic therapy in
      clopidogrel resistant patient.
AB  - Sixty-year-old woman admitted with dyspnea and cough. Three weeks ago she
      underwent primary stenting for acute anterior myocardial infarction and received
      antiplatelet therapy (clopidogrel). Echocardiography and left ventriculography
      revealed left ventricular segmental dysfunction at anterolateral-apical region
      but no thrombus. On last admission, despite the clopidogrel therapy,
      echocardiography showed giant-partly mobil thrombus obliterated half of the left
      ventricle. Slow infusion of thrombolytic therapy was given and complete lysis
      occurred with uneventful course. Disclosure of such a rapidly evolving giant left
      ventricular thrombus in the clopidogrel non-responder is a rare clinical problem
      with potentially catastrophic consequences. Slow infusion of thrombolytic therapy
      may be effective and life saving.

PMID- 14574078
TI  - In vivo cardioprotection by N-acetylcysteine and isosorbide 5-mononitrate in a
      rat model of ischemia-reperfusion.
AB  - AIMS: We evaluated the effect of N-acetylcysteine (NAC, infused i.v.), isosorbide
      5-mononitrate (IS5MN, by gavage), or their combination on cardiac injury in an in
      vivo rat model of 30-min ischemia followed by 24 hours or 7 days of reperfusion.
      RESULTS: When administered immediately prior to reperfusion with continuous
      infusion for 24 h, the combination of NAC + IS5MN reduced infarct size (29 +/- 6
      vs. 59 +/- 4% area-at-risk, p < 0.01) and the infiltration of polymorphonuclear
      leukocytes (226 +/- 15 vs. 315 +/- 18 cells mm(-2) of area-at-risk, p = 0.002)
      and monocytes/macrophages (118 +/- 8 vs. 194 +/- 22 cells mm(-2), p = 0.012),
      compared to vehicle. NAC or IS5MN alone did not reduce infarct size at 24 hours
      of reperfusion. The same dose regimen of NAC and IS5MN did not reduce infarct
      size with permanent ischemia for 24 hours not followed by reperfusion. After 7
      days of reperfusion (3 days of treatment with NAC + IS5MN or vehicle and 4 days
      of wash-out), infarct size was similar in the vehicle and NAC + IS5MN groups, but
      LV end-diastolic pressure and diastolic LV chamber wall stress were significantly
      lower in the animals treated with NAC + IS5MN (5 +/- 1 mmHg and 62 +/- 7 dyne mm(
      2), respectively) compared to vehicle (9 +/- 1 mmHg and 123 +/- 18 dyne mm(-2), p
      < 0.05). CONCLUSIONS: We demonstrate in a rat model of cardiac ischemia
      reperfusion treated with NAC and IS5MN, according to a regimen that mimicked a
      clinical situation (drugs started at time of reperfusion), that the short-term
      benefit seen after 24 h of reperfusion (51% reduction of infarct size) is
      maintained after one week, possibly through modulation of the inflammatory
      response to cardiac injury.

PMID- 14574079
TI  - Post-ischemic treatment with dipyruvyl-acetyl-glycerol decreases myocardial
      infarct size in the pig.
AB  - The beneficial effects of pyruvate in organ reperfusion injury have been
      documented, however the therapeutic use of pyruvate has been hindered by the lack
      of an appropriate delivery method. Pyruvic acid is unstable and high rates of
      sodium pyruvate infusion are toxic. Dipyruvyl-acetyl-glycerol (DPAG) ester was
      developed as a novel method for intravenous pyruvate delivery at a high rate
      without sodium overload. We tested the ability of DPAG to reduce myocardial
      infarct size when administered after severe myocardial ischemia in an
      anesthetized open-chest pig model of ischemia-reperfusion injury. Ischemia was
      induced by total occlusion of the distal 2/3 of the left anterior descending
      coronary artery for one hour, followed by two hours of reperfusion. Animals were
      either untreated (n = 7), or treated with intravenous DPAG (8.0 mg/kg(-1). min(
      1), n = 8) during the two hours of reperfusion. Infarct size was measured on
      blinded samples using tetrazolium staining. The DPAG treated group had elevated
      pyruvate levels (0.82 +/- 0.07 mM) and reduced infarct size (20.1 +/- 4.2% of the
      volume at risk, compared to 30.8 +/- 4.6% in the untreated animals (p < 0.05)),
      with no difference in blood pressure or heart rate between groups. In conclusion,
      an intravenous infusion of DPAG safely increases arterial pyruvate concentration
      and reduces myocardial infarct size following myocardial ischemia.

PMID- 14574081
TI  - Effects of olmesartan, an angiotensin II receptor blocker, on mechanically
      modulated genes in cardiac myocytes.
AB  - BACKGROUND: Angiotensin II plays an important role in cardiac hypertrophy or
      remodeling. Angiotensin II receptor blockers (ARB) are clinically useful for the
      treatment of hypertension and heart failure. However, the molecular effects of
      ARB in the mechanically-stressed myocardium have not been completely defined. We
      investigated the effects of ARB on mechanically-modulated genes in cardiac
      myocytes. METHODS: We used powerful DNA microarray technology to study the
      effects of the ARB, CS-886 (olmesartan), on genes modulated in neonatal rat
      cardiac myocytes using mechanical stimuli. Mechanical deformation was applied to
      a thin and transparent membrane on which neonatal rat cardiac myocytes were
      cultured in the presence or absence of RNH-6270, an active metabolite of CS-886.
      Expression profiles of 8000 rat genes using the Affymetrix GeneChip (Rat Genome
      U34A) were investigated with mRNA obtained from the samples above. RESULTS: Nine
      genes induced under 4% mechanical strain were significantly suppressed by RNH
      6270 in rat cardiac myocytes: monoamine oxidase B, neuromedine B receptor,
      olfactory receptor, synaptotagmin XI, retinol-binding protein, and 4 expressed
      sequence tags (ESTs). In contrast, 21 genes suppressed under mechanical strain
      were significantly restored by RNH-6270: major acute phase alpha 1-protein, Sp-1,
      Bcl-Xalpha, JAK2, 2 genes encoding detoxification, few genes for receptor,
      structure, metabolism or ion channel, and 10 ESTs. CONCLUSIONS: As some of these
      genes may be involved in promoting or modulating cardiac remodeling, these
      findings suggest that ARB may affect cardiovascular morbidity and mortality
      partially via these molecular alterations.

PMID- 14574080
TI  - Comparison between ischaemic and anisomycin-induced preconditioning: role of p38
      MAPK.
AB  - To further evaluate the significance of p38 MAPK as trigger or mediator in
      ischaemic preconditioning, anisomycin and SB 203580 were used to manipulate its
      activation status. Special attention was given to the concentration of the drugs
      and protocols used. The isolated perfused rat heart, subjected to either 25 min
      global ischaemia or 35 min regional ischaemia, was used as experimental model.
      This was preceded by anisomycin (2 or 5 muM: 3 x 5 min; 5 muM: 5 min or 10 min; 5
      muM: 10 min + 10 min washout or 20 muM: 20 min) or SB 203580 (2 muM: 3 x 5 min;
      before and during 3 x 5 min or 1 x 5 min ischaemic preconditioning; 10 min).
      Endpoints were functional recovery during reperfusion and infarct
      size.Anisomycin, regardless of the protocol, reduced infarct size, but did not
      improve functional recovery. In a number of experiments activation of JNK by
      anisomycin was blocked by SP 600125 (10 muM). SP 600125 had no effect on the
      anisomycin-induced reduction in infarct size. SB 203580 when administered for 10
      min before sustained ischaemia, improved functional recovery and reduced infarct
      size. SB 203580 could not abolish the beneficial effects of a multi-cycle
      preconditioning protocol, but it significantly reduced the outcome of 1 x 5 min
      preconditioning. In all hearts improved functional recovery and reduction in
      infarct size were associated with attenuation of p38 MAPK activation during
      sustained ischaemia-reperfusion. The results indicate that activation of p38 MAPK
      acts as a trigger of preconditioning, while attenuation of its activation is a
      prerequisite for improved recovery and a reduction in infarct size.

PMID- 14574082
TI  - Refractoriness and conduction interaction during modulation of non-ischemic
      ventricular fibrillation by flecainide.
AB  - PURPOSE: To study refractoriness and conduction interaction during modulation of
      non-ischemic ventricular fibrillation (VF) by flecainide. METHODS: Isolated
      feline and rabbit hearts were used. (a) In the feline hearts (n = 8),
      electrophysiological parameters were measured before and after flecainide
      administration (0.6, 1.2 x 10(-6) M). During pacing the parameters were:
      epicardial conduction time, refractoriness and 1:1 pacing/response capture.
      During 8 min of electrically-induced tachyarrhythmias they included heart rate
      and normalized entropy reflecting the degree of organization. (b) In rabbit
      hearts (n = 4), three-dimensional mapping was performed before and after
      flecainide administration (2 x 10(-6) M). To follow changes in organization,
      local RR-intervals and differences in activation time between adjacent epicardial
      electrodes were measured immediately and 80 sec after VF induction. RESULTS: In
      feline hearts with flecainide, fibrillation was more difficult to induce, more
      frequently terminated spontaneously and was slower and more organized; conduction
      time was markedly lengthened, and refractoriness less than 1:1 capture, was
      moderately prolonged. An inverse correlation was observed between arrhythmia
      properties, rate and organization, and changes in refractoriness and conduction
      time. In rabbit, the number of wave fronts was reduced, RR-intervals were
      prolonged but at the same time activation time differences between adjacent
      electrodes were smaller following flecainide administration. CONCLUSIONS: It is
      suggested that flecainide modulation of VF properties is associated with
      conduction suppression and refractoriness prolongation, which act in a
      synergistic, additive way.

PMID- 14574083
TI  - Serum MCP-1 and VEGF levels are not affected by inhibition of the renin
      angiotensin system in patients with acute myocardial infarction.
AB  - Monocyte chemoattractant protein-1 (MCP-1) and vascular endothelial growth factor
      (VEGF) stimulate angiogenesis in ischemic tissues, and both of their expression
      are stimulated by angiotensin II. We measured the serum concentrations of MCP-1
      and VEGF in patients with acute myocardial infarction (AMI) and investigated the
      effects of an early administration of angiotensin-converting enzyme inhibitor
      (ACEI) and angiotensin II type 1 receptor blocker (ARB) on their levels. Thirty
      six patients with AMI were divided randomly into 3 therapeutic groups; the ACEI
      perindopril, the ARB candesartan and control (without perindopril and
      candesartan), and the drugs were administered within 36 hours after the onset of
      AMI. Peripheral blood mononuclear cells (PBMC) obtained from the patients were
      incubated for 24 hours. The levels of MCP-1 and VEGF in the serum and the
      supernatant of PBMC were measured by ELISA. The serum MCP-1 and VEGF levels in
      AMI patients at the time of admission were not significantly different from those
      in healthy control subjects, but both MCP-1 and VEGF levels in the patients were
      increased significantly after 7 days. There was no significant difference in the
      serum MCP-1 and VEGF levels among the 3 therapeutic groups. The production of MCP
      1 and VEGF by PBMC was also increased in AMI patients compared with healthy
      control subjects, and there was also no difference in their production among the
      3 therapeutic groups. In conclusion, circulating MCP-1 and VEGF levels and their
      production by PBMC are elevated during the course of AMI, and early
      administration of ACEI and ARB does not affect their levels.

PMID- 14574084
TI  - Comparison of the new cardioselective beta-blocker nebivolol with bisoprolol in
      hypertension: the Nebivolol, Bisoprolol Multicenter Study (NEBIS).
AB  - OBJECTIVES: The aim of the present study was to evaluate the antihypertensive
      efficacy of the highly beta(1)-selective adrenergic antagonist nebivolol in
      comparison with bisoprolol in the treatment of mild to moderate essential
      hypertension. METHODS: This multicenter, single-blind, randomized, parallel-group
      16-week study involved a 4-week placebo run-in, followed by a 12-week treatment
      period (5 mg nebivolol or 5 mg bisoprolol). Patients (n = 273) eligible for the
      study had a sitting diastolic blood pressure (DBP) between 95 and 110 mm Hg and a
      systolic blood pressure (SBP) </=180 mm Hg at the end of the placebo run-in
      period. The primary endpoint of the study was the percentage of responders
      achieving DBP normalization (</=90 mm Hg) or a DBP reduction of at least 10 mm
      Hg. RESULTS: The baseline SBP and DBP were similar in the two groups. Both SBP
      and DBP decreased gradually and significantly upon treatment. The two treatments
      had similar effects on the mean change from the baseline for both DBP (nebivolol 
      15.7 +/- 6.4 mm Hg vs. bisoprolol -16.0 +/- 6.8 mm Hg) and SBP. A high proportion
      of responders was noted in both groups (nebivolol 92.0% vs. bisoprolol 89.6%) and
      there was no significant difference between the treatments. The overall number
      and incidence of spontaneously reported adverse events were slightly, but not
      significantly lower for nebivolol (8 events; 5.8%) than for bisoprolol (12
      events; 8.9%). CONCLUSIONS: The findings of the present trial indicate that 5 mg
      nebivolol once daily is an effective antihypertensive agent. It can therefore be
      recommended as a useful alternative first-line treatment option for the
      management of patients with mild to moderate essential hypertension.

PMID- 14574085
TI  - The safety of HMG-CoA reductase inhibitors in special populations at high
      cardiovascular risk.
AB  - Controlled clinical studies and clinical experience over many years have proven
      that virtually all patients benefit from lipid-lowering therapy with statins,
      even those with normal LDL cholesterol levels. Several recent large outcome
      trials have further demonstrated the clinical benefits and safety of statins in
      patients with a wide-range of high risks for cardiovascular disease. Those
      patients at highest absolute cardiovascular risk generally have the most to gain
      from statin therapy. A variety of statins are available to lower plasma lipids to
      guideline levels, but all differ in their pharmacokinetic properties, drug
      interaction profiles, and risk of myotoxicity. This has been highlighted by the
      withdrawal of cerivastatin from the market as a result of serious safety
      concerns. This review examines the safety and effectiveness of statins in special
      populations at high risk of cardiovascular disease-patients with coronary heart
      disease, dyslipidaemia, diabetes, hypertension, nephrotic disease, HIV, organ
      transplant patients and the elderly-with a focus on clinically relevant
      differences in the properties of individual statins that may influence the risk
      of drug interactions and side effects.

PMID- 14574086
TI  - Independent clinical correlates of severe alcohol withdrawal.
AB  - This retrospective cohort study sought to identify clinical variables that
      independently correlate with severe alcohol withdrawal and to quantify risk in a
      clinically useful manner. The records of 284 inpatients admitted to an acute
      detoxification unit at a Veterans Affairs teaching hospital were reviewed.
      Clinical data were recorded on standardized forms at the time of admission and
      abstracted by a physician reviewer. Alcohol withdrawal severity was prospectively
      measured with the revised Clinical Institute Withdrawal Assessment for Alcohol
      (CIWA-Ar) scale. Seventy-one patients (25% of cohort) had severe withdrawal. We
      identified six independent correlates of severe withdrawal: use of a morning eye
      opener (adjusted odds ratio [OR], 5.6; 95% confidence interval [CI], 1.2-25.9),
      an initial CIWA-Ar score > or =10 (OR, 5.1; 95% CI, 2.4-10.6), a serum aspartate
      aminotransferase > or =80 U/L (OR, 4.2; 95% CI, 2.0-8.8), past benzodiazepine use
      (OR, 3.6; 95% CI, 1.3-9.9), self-reported history of "delirium tremens" (OR, 2.9;
      95% CI, 1.3-6.2), and prior participation in two or more alcohol treatment
      programs (OR, 2.6; 95% CI, 1.3-5.6). Significantly higher risk was observed in
      subjects with three or more independent correlates. In conclusion, several
      readily available clinical variables correlate with the occurrence of severe
      alcohol withdrawal. Ascertainment of these variables early in the course of
      alcohol withdrawal has the potential to improve triage and treatment decisions.

PMID- 14574088
TI  - A modified version of the CAGE as an indicator of alcohol abuse and its
      consequences among undergraduate drinkers.
AB  - In March of 1999, we conducted a cross-sectional, web-based survey using a random
      sample of 2041 undergraduate students attending a large, public university in the
      Midwest. The sample was recruited via e-mail and students completed the Web
      survey from their computer terminals. Toward the goal of establishing the
      usefulness of the CAGE when screening undergraduates for alcohol misuse, we first
      examined the proportion of undergraduates with a positive score on a modified
      version of the CAGE and then determined the correlates of a positive CAGE score
      (e.g. alcohol consumption, fear of addiction, etc.). We found preliminary
      evidence that the question "Have you been afraid you might be alcoholic" may be
      the best identifier, when compared to the modified CAGE, of at-risk students.

PMID- 14574087
TI  - Condom use behaviors in HIV-infected African American crack cocaine users.
AB  - The purpose of this study was to investigate sexual risk behaviors and factors
      associated with consistent condom use of HIV+ African Americans receiving HAART
      who smoke crack. Participants were African Americans in Houston, Texas and over
      18, being treated for HIV, and reported currently using crack. Measures included
      demographic variables, sexual behaviors, drug use, and nine psychosocial scales
      and seven escape scales. One hundred thirty seven participated in the study.
      Condom use was low across all partner types. Regression analyses revealed two
      demographic variables, and two psychosocial and one escape scale were
      significantly associated with intention to use condoms. One of the more alarming
      findings of this study concerns the large number of individuals who know they are
      HIV positive yet continue to have unprotected sex. The inconsistent condom use by
      these HIV+ individuals threatens the progress that has been made to stem the
      epidemic.

PMID- 14574089
TI  - Physicians' attitudes regarding reporting alcohol-impaired drivers.
AB  - Our objective was to examine attitudes on reporting alcohol-impaired drivers by
      physicians of different specialties who are most likely to treat motor vehicle
      crash (MVC) patients. Specific objectives included examining 1) degree of comfort
      with reporting to police or Department of Motor Vehicles (DMV), 2) variability in
      attitudes across specialties surveyed, 3) perceived barriers to reporting, and 4)
      general attitudes on treating alcoholism. Physicians reported that they felt more
      comfortable with reporting to a medical review board of DMV than to police in all
      three of the case examples, which included treating a patient who is a clinically
      diagnosed alcohol-impaired MVC driver (66% DMV report, 36% police report), MVC
      driver at legal limit of blood alcohol concentration (63% DMV report, 32% police
      report), and an MVC driver with a very high blood alcohol concentration (81% DMV
      report, 53% police report). There was no difference between specialties in
      comfort with reporting, though emergency medicine physicians were less likely to
      screen and refer patients for counseling. The primary reasons given for not
      reporting an alcohol-impaired driver were physician-patient confidentiality and
      perceived threat of civil action by patients.

PMID- 14574090
TI  - A revision of Platybothrium Linton, 1890 (Tetraphyllidea: Onchobothriidae), with
      a phylogenetic analysis and comments on host-parasite associations.
AB  - A revision of Platybothrium Linton, 1890 is presented, based on available type
      and voucher material, as well as extensive new collections from elasmobranchs
      belonging to the Carcharhinidae (requiem sharks) and Sphyrnidae (hammerhead
      sharks). All 10 nominal Platybothrium species are treated or redescribed herein.
      Four of these 10 nominal species, in addition to one former member of
      Dicranobothrium Euzet, 1953, are considered valid members of Platybothrium. Five
      new Platybothrium species are described: P. angelbahiense n. sp. ex Carcharhinus
      leucas, P. coshtaprum n. sp. ex C. plumbeus, P. jondoeorum n. sp. ex Negaprion
      acutidens and C. melanopterus, P. kirstenae n. sp. ex C. obscurus, and P.
      tantulum n. sp. ex Sphyrna lewini and S. zygaena. Sixty-three morphological
      characters were employed in cladistic analyses of nine Platybothrium species and
      five outgroup species. Coding and analysis strategies were varied to assess the
      effects of coding inapplicable characters as missing or as a separate character
      state, and of excluding characters for which data are missing in more than 10% of
      the taxa. The analysis in which inapplicable characters were coded as a separate
      character state and no characters were excluded produced the best-supported and
      most conservative estimate of the interrelationships of Platybothrium spp.
      Platybothrium appears to be a monophyletic assemblage, with the most basal
      species being P. spinulifera Southwell, 1912. The group of species possessing an
      accessory piece between the hooks forms a clade within the genus. Species lacking
      an accessory piece, which had previously been placed in Dicranobothrium Euzet,
      1953, do not appear to be each other's closest relatives; thus, Dicranobothrium
      is considered a synonym of Platybothrium. An examination of host associations
      indicated that Platybothrium species are broadly distributed among, and entirely
      restricted to, carcharhinid and sphyrnid shark species. Most Platybothrium
      species exhibit oioxenous host-specificity, with all but two species each
      parasitising only a single host species. In several host species, multiple
      Platybothrium congeners parasitise the same host individual, a phenomenon not
      previously reported for Platybothrium.

PMID- 14574091
TI  - ITS rDNA sequences of Pomphorhynchus laevis (Zoega in Muller, 1776) and P. lucyi
      Williams and Rogers, 1984 (Acanthocephala: Palaeacanthocephala).
AB  - The internal transcribed spacers (ITS-1 and ITS-2) of the ribosomal RNA gene of
      Pomphorhynchus laevis (Zoega in Muller, 1776) (Acanthocephala) isolated from
      various fish species across Central and Southern Europe were compared with those
      of P. lucyi Williams and Rogers, 1984 collected from the largemouth bass
      Micropterus salmonoides Boulenger from the USA. The nucleotide sequences of ITS
      regions of P. laevis from minnows Phoxinus phoxinus (L.) and chub Leuciscus
      cephalus (L.) from two distant localities in the Slovak Republic were found to be
      100% identical. The ITS-1 and ITS-2 of P. laevis from chub from the Czech
      Republic and Italy were also mutually identical, but significantly different from
      Slovak worms (88.7% identity for ITS-1, 91.3% identity for ITS-2). A fifth sample
      collected from Barbus tyberinus Bonaparte from Italy was very similar to the
      sympatric Italian isolate from chub, possessing four nucleotide substitutions in
      ITS-1 (98.4% identity). The ITS rDNA sequences of P. lucyi differed significantly
      from those of P. laevis; the values of identity were 51.8-56.1% for ITS-1 and
      63.1-65.3% for ITS-2, and were significantly higher than the range of P. laevis
      within-species variability. The results based on the ITS sequences confirmed the
      occurrence of strains in P. laevis from Continental Europe which are well defined
      by molecules but reveal only slight differences in their morphology.

PMID- 14574092
TI  - First report of a species of Folliculovarium Gu and Shen, 1983 (Bucephalidae:
      Prosorhynchinae) from European marine waters, with the description of F.
      mediterraneum n. sp.
AB  - Folliculovarium mediterraneum n. sp. is described and figured in detail from the
      intestine of the Mediterranean moray eel Muraena helena (Muraenidae) in the
      Scandola Nature Reserve, off Corsica in the Western Mediterranean. This new
      species closely resembles F. gymnothoracis Gu and Shen, 1983 and F. xishaense Gu
      and Shen, 1983 from marine fishes off China, but it may differ from both in not
      having specialised circum-rynchal spines. It differs from the former by having
      slightly larger eggs and a longer oesophagus, and from F. xishaense by having
      tegumental spines, a longer oesophagus and a non-related host (an eel rather than
      a serranid). The status of Folliculovarium, which was recently treated as a genus
      inquirendum by Overstreet and Curran (2002), is clarified by its multilobed
      rather than follicular ovary and other features, and remains in the
      Prosorhynchinae (Bucephalidae).

PMID- 14574093
TI  - Raillietiella trachea n. sp., a pentastomid from the trachea of an oriental white
      backed vulture Gyps bengalensis taken in Pakistan, with speculation about its
      life-cycle.
AB  - A cephalobaenid pentastomid, Raillietiella trachea n. sp., from the trachea of a
      fledgling oriental white-backed vulture Gyps bengalensis taken in Punjab
      Province, Pakistan, is described. This is the first record of a pentastomid from
      a fully terrestrial bird. Overall, gross morphology was typical of Raillietiella
      Sambon, 1910 in most respects. However, the hooks of R. trachea were of equal
      size, whereas in other members of the genus anterior hooks are smaller than the
      posterior hooks. The diagnosis of R. trachea was made on the basis of four near
      patent females, all of which contained relatively few eggs (c.570), all at the
      same stage of maturity. Comparison with the only other genus known to infect
      birds (two species of Reighardia Ward, 1899 from the air-sacs of marine birds)
      revealed striking parallels in this aspect of the functional anatomy of the
      female reproductive tract. As far as we know, this mode of egg-production is not
      found in other raillietiellids. Extrapolating primarily from the experimental
      life-cycle studies of Reighardia sternae (Diesing, 1864) Ward, 1899, we surmise
      that the life-cycle of R. trachea has to be direct and that parasite behaviour is
      an integral part of parasite transmission. The evidence suggests that
      transmission is from vulture-to-vulture, per os.

PMID- 14574094
TI  - Intimate partner violence and safer sex negotiation: effects of a gender-specific
      intervention.
AB  - This study examined the effects of a gender-specific HIV/STD prevention
      intervention with two dosage levels (four-session, eight-session) among women
      reporting physical abuse by a current or recent (past year) intimate partner.
      From 360 women included in the full randomized trial, we conducted subgroup
      analyses among 152 women who experienced partner physical abuse within the past
      year. Unprotected vaginal and anal sex occasions and negotiation skills were
      examined as outcomes. We also assessed whether the intervention increased
      previously abused women's subsequent risk of physical abuse. Among abused women,
      those in the eight-session, but not the four-session, intervention decreased
      their unprotected sex occasions or maintained consistent safer sex at both 1
      month (OR = 3.63, 95% CI = 1.50-8.80) and 1-year (OR = 2.88, 95% CI = 1.17-7.10)
      postintervention. In the short-term, abused women in both the four- and eight
      session groups had a greater odds of using an alternative strategy (e.g.,
      refusal, "outercourse," or mutual testing) and of having a safer sex discussion
      with their partners relative to their controls, and they scored higher on
      intention to negotiate safer sex. The intervention did not increase or decrease
      the incidence of subsequent abuse during the 1-year follow-up period. A gender
      specific intervention that focuses on negotiation skills in the context of
      potentially abusive partners benefits, and does not appear to harm, recently
      abused women.

PMID- 14574095
TI  - Assessing reliability of early adolescent girls' reports of romantic and sexual
      behavior.
AB  - Increasing rates of HIV among urban adolescents have raised concerns about their
      participation in sexual risk behaviors. The accuracy of adolescents' sexual
      reports is critical to the assessment of risk, which may later guide the
      development of public policy, interventions, and education efforts. The data
      presented here are part of a larger study on a range of sexual behaviors and
      cognitions believed to be important regarding adolescent girls' sexual choices
      and decision-making. Our goal here was to assess the test-retest reliability of
      early adolescent girls' reports of their romantic and sexual experiences. This
      information will contribute to our limited information base regarding sexuality
      research with early adolescents. Fifty urban African American and Latina girls
      between the ages of 12 and 14 years were recruited from community settings around
      New York City. A battery of sexual behavior and sexual cognition measures was
      administered by interviewers at two time points separated by a 3-week interval.
      Results indicated that the girls were highly reliable in reporting their sexual
      experiences, especially those experiences related to age of first romantic and
      sexual milestone experiences.

PMID- 14574096
TI  - Zoophilia in men: a study of sexual interest in animals.
AB  - This article presents a study of 114 self-defined zoophile men who were
      researched primarily through the use of an on-line questionnaire. We describe how
      the participants acquired the identity label of zoophile, what it meant to them,
      and their relationships among themselves. Also examined are how they eroticized
      animals and how human and feral characteristics combined to form this object
      choice. Finally, participants' sexual profiles with animals and humans, and how
      the balance of animal and human desires creates different forms of zoophilia, are
      described.

PMID- 14574097
TI  - Love at first fright: partner salience moderates roller-coaster-induced
      excitation transfer.
AB  - This study examined the effects of residual nervous system arousal on perceptions
      of sexual attraction. Researchers approached individuals (males, n = 165;
      females, n = 135) at amusement parks as they were either waiting to begin or as
      they had just gotten off a roller-coaster ride. Participants were shown a
      photograph of an average attractive, opposite-gendered individual and asked to
      rate the individual on attractiveness and dating desirability. Participants were
      also asked to rate their seatmates' levels of attractiveness. Consistent with the
      predictions of excitation transfer theory, for males and females riding with a
      nonromantic partner, ratings of attractiveness and dating desirability toward the
      photographed individual were higher among persons exiting than entering the ride.
      Among persons riding with a romantic partner, there were no significant
      differences in attractiveness or dating desirability ratings between persons
      entering and exiting the ride. The findings are discussed in terms of the
      potential moderator effects of a salient romantic partner on excitation transfer.

PMID- 14574098
TI  - Sexual media use by young adults in Hong Kong: prevalence and associated factors.
AB  - The prevalence of sexual media use, and factors associated with it, among Chinese
      young adults were studied in Hong Kong. Questions on use of sexual media were
      asked as part of a youth sexuality study conducted by the Family Planning
      Association in 1996. In a population-based cross-sectional study, 517 men and 447
      women aged 18-27 years completed an anonymous structured self-administered
      questionnaire. The overall prevalence [95% confidence interval (CI)] of ever
      purchased or rented any type of sexual media was 57.8% (54.7-60.9). More men
      (70.2%; 95% CI: 66.3-74.2) than women (43.4%; 95% CI: 38.8-48.0) used sexual
      media. Of 31 independent variables tested by stepwise logistic regression, seven
      variables significantly predicted sexual media use: age (adjusted odds ratio OR =
      1.5 for 21-24 and 1.8 for 25-28, versus 20 or below), male gender (OR = 3.0),
      number of sexual partner (OR = 2.2 for one and 2.8 for two or more partners),
      masturbation in the past week (OR = 3.2), being out of school (OR = 1.5), quarrel
      with family member in past 6 months (OR = 1.8), and religion (OR = 1.6 for no
      religion and 3.4 for traditional Chinese religion, versus Christians) (all
      adjusted OR:p < 0.05).

PMID- 14574099
TI  - Sexual risk-taking in gay men: the relevance of sexual arousability, mood, and
      sensation seeking.
AB  - This paper examined the relationship of three aspects of personality to sexual
      risk-taking in gay men: (1). sexual arousability, as propensity for sexual
      excitation, and propensity for inhibition of sexual arousal in the face of threat
      (measured by the Sexual Excitation, SES, and Sexual Inhibition, SIS1, SIS2,
      scales); (2). the relation between negative mood and sexuality; and (3).
      sensation seeking. Risk-taking was assessed for the past 6 months in relation to
      unprotected anal intercourse (UAI), oral sex, number of casual partners, and
      patterns of cruising behavior. A combination of number of partners and use of
      condoms was used to derive a "longer-term risk" grouping. Two patterns of
      association were identified. UAI and high risk oral sex were more likely in those
      with low inhibition of sexual response due to "threat of performance
      consequences" (i.e., low SIS2) and low trait anxiety (low STAI). High numbers of
      casual partners and frequent cruising were associated with increased sexual
      interest in states of depression and high propensity for sexual excitation (SES).
      Higher "long-term risk" was also associated with low SIS2. Unexpectedly, high
      SIS1, which is strongly related to vulnerability to erectile failure, was also
      predictive of higher long-term risk. Possible reasons for this are discussed.
      Disinhibition from the Sensation Seeking Scales was a positive predictor of all
      types of sexual risk assessed. All three aspects of personality are of potential
      relevance to designing better interventions to reduce high risk sexual behavior
      and in evaluating their effectiveness.

PMID- 14574100
TI  - Self-reported head injuries before and after age 13 in pedophilic and
      nonpedophilic men referred for clinical assessment.
AB  - Previous research has found that pedophilic men referred for clinical assessment
      of their sexual behavior are more likely to report that they suffered head
      injuries before their 13th birthday than are nonpedophilic men referred for the
      same purpose. This study investigated whether pedophilic patients are also more
      likely to report head injuries after their 13th birthday. The 685 participants
      represented all patients with usable data from a consecutive series of men
      referred to a clinical laboratory specializing in phallometric assessment of
      erotic preferences. In addition to phallometric testing, participants were
      administered a brief neuropsychological test battery and a companion interview,
      which included questions on head injury, drug abuse, and childhood diagnosis of
      attention-deficit/hyperactivity disorder. The results showed that the pedophilic
      patients reported more head injuries before age 13 than did the nonpedophilic
      patients, but they did not report more head injuries after age 13. The
      association between pedophilia and childhood head injuries could mean either that
      subtle brain damage after birth increases a boy's risk of pedophilia, or that
      neurodevelopmental problems before birth increase a boy's accident-proneness
      along with his risk of pedophilia. Additional analyses showed that self-reported
      head injuries before age 13 were associated with attentional problems and with
      left-handedness; in contrast, head injuries after age 13 were associated with
      drug abuse and promiscuity. These analyses suggest that, among patients with
      primary presenting complaints of sexual rather than cognitive problems, childhood
      head injuries cluster with neuropsychological phenomena, whereas later head
      injuries cluster with lifestyle variables.

PMID- 14574101
TI  - Novel Leuconostoc citreum starter culture system for the fermentation of kimchi,
      a fermented cabbage product.
AB  - To determine the dominant microorganisms involved in kimchi fermentation and to
      examine their effect on kimchi fermentation, we randomly isolated and
      characterized 120 lactic acid bacteria from kimchi during a 5-day fermentation at
      15 degrees C. Leuconostoc citreum was dominant during the early and mid-phases of
      kimchi fermentation whereas Lactobacillus sake/Lactobacillus curvatus or
      Lactobacillus brevis were found during later stages. Eighty-two out of 120
      isolates (68%) were identified as Leuconostoc citreum by means of a polyphasic
      method, including 16S rDNA sequencing and DNA/DNA hybridization. A few Weissella
      confusa-like strains were also isolated during the mid-phase of the fermentation.
      Strain IH22, one of the Leuconostoc citreum isolates from kimchi, was used as an
      additive to evaluate growth and acid production in kimchi fermentation. This
      strain was consistently over 95% of the population in IH22-treated kimchi over a
      5-day fermentation, while heterogeneous lactic acid bacteria were observed in the
      control kimchi. The pH in IH22-treated kimchi dropped rapidly but was stably
      maintained for 5 days, compared to its slow and prolonged decrease in the control
      kimchi. These results indicate that Leuconostoc citreum IH22 dominates over and
      retards the growth of other lactic acid bacteria in kimchi, suggesting it can be
      used as a bacterial starter culture to maintain the quality of kimchi for
      prolonged periods.

PMID- 14574102
TI  - Nature and mode of action of NAD and ATP dephosphorylating enzyme from
      Aspergillus terreus DSM 826.
AB  - NAD and ATP were dephosphorylated by Aspergillus terreus extracts optimally at pH
      8 and 40 degrees C. The data obtained indicate that one phosphohydrolase was
      involved in the cleavage of all the phosphate linkages of these two energy
      carrying molecules, and also indicate that this enzyme can be classified as a non
      specific alkaline phosphatase. This is based on the following criteria: during
      fractionation of the enzymes of the extracts, using Sephadex G-200 column
      chromatography, the recorded elution diagram showed only one phosphohydrolase
      activity peak and this peak was the same with NAD, ATP, inorganic pyrophosphate
      and phenyl phosphate as substrates; the activity profiles with these four
      substrates were similar; and these four substrates were hydrolyzed at almost
      constant relative rates. Moreover, the activities of the pooled fractions with
      these different substrates responded similarly on changing some experimental
      conditions, such as addition of fluoride to the reaction mixtures or exposing the
      enzyme preparation to temperatures above 40 degrees C. Chromatographic detection
      of the intermediates and the products formed during the progression of NAD and
      ATP dephosphorylation by the most purified fraction of this enzyme was found to
      be consistent with the following mode of its action:

PMID- 14574103
TI  - Cis-2', 3'-dihydrodiol production on flavone B-ring by biphenyl dioxygenase from
      Pseudomonas pseudoalcaligenes KF707 expressed in Escherichia coli.
AB  - Escherichia coli JM109 strains expressing either toluene dioxygenase from
      Pseudomonas putida F1 or biphenyl dioxygenase from Pseudomonas pseudoalcaligenes
      KF707 were examined for their ability to catalyze flavones. Biphenyl dioxygenase
      produced metabolites from flavone and 5,7-dihydroxyflavone which were not found
      in the control experiments. The absorption maxima of UV-visible spectra for the
      metabolites from flavone and 5,7-dihydroxyflavone were found at 337 and 348 nm
      respectively by using a photodiode array detector in the HPLC. Liquid
      chromatography/mass spectroscopy (LC/MS) showed molecular weights 256 and 288 for
      the metabolites, respectively. The metabolite of flavone, which was isolated and
      purified from the bacterial culture, was further subjected to analysis by 1H and
      13C nuclear magnetic resonance (NMR) spectroscopy. Based on the LC/MS and NMR
      results, biphenyl dioxygenase inserted oxygen at C2' and C3' on the B-ring of
      flavone, resulting in the formation of flavone cis-2', 3'-dihydrodiol (2-[3,4
      dihydroxy-1.5-cyclohexadienyl]-4H-chromen-4-one). Since this product is not found
      in Chemical Abstracts, this compound is considered a novel one. In addition,
      biotransformation of flavones by biphenyl dioxygenase suggested a potential role
      of bacterial dioxygenase to synthesize novel compounds from plant secondary
      metabolites.

PMID- 14574105
TI  - Genetic determination of ploidy level in Xanthophyllomyces dendrorhous.
AB  - Xanthophyllomyces dendrorhous (formely Phaffia rhodozyma) is a basidiomycetous
      yeast-like fungus that produces carotenoids useful for the food industry.
      Recently, its sexual cycle was reported but little is known about its genetic
      constitution. To inquire into the ploidy state of X. dendrorhous, biased mutant
      spectrum, genetic complementation and mitotic recombination analysis were used. A
      wild-type strain was subjected to N-methyl-N'-nitro-N-nitrosoguanidine mutagenic
      treatment. Auxotrophic and carotene mutants were forced to revert to the wild
      type phenotype. Pigment producing and prototroph revertants behaved as diploid
      except for adenine less mutants. These results are in agreement with the limited
      spectrum of auxotrophs obtained in this strain for the ADE1 locus. To analyze the
      genetic characteristic of the adenine genetic marker of X. dendrorhous,
      protoplast fusion experiments with several adenine less mutants were performed.
      The experiments presented in this work suggest that the ATCC 2430 (UDC 67-385)
      strain of X. dendrorhous is diploid and a heterozygous constitution is proposed
      for the ADE1 locus.

PMID- 14574104
TI  - Distribution of virulence genes in clinical and environmental isolates of
      Aeromonas spp.
AB  - The distribution and phenotypic activity of the genes encoding for serine
      protease, glycerophospholipid-cholesterol acyltransferase, lipases,
      aerolysin/hemolysin and DNases were investigated in 234 isolates identified by
      16S rDNA-RFLP representing all the species of Aeromonas. The former three genes
      were found to be highly conserved among the genus. Aerolysin/hemolysin and DNase
      genes and beta-hemolytic activity were significantly more frequent in clinical
      than in environmental isolates. Aerolysin/hemolysin and serine protease genes
      were present in all beta-hemolytic strains supporting serine protease as possibly
      important for the activation of the former gene. The high prevalence of virulence
      factors in clinical isolates indicates that they may play a role in the
      mechanisms of pathogenesis of these microorganisms.

PMID- 14574106
TI  - Evolutionary and structural diversity of fungal laccases.
AB  - Fungal laccases have been extensively exploited for industrial purposes and there
      is a wealth of information available regarding their reaction mechanism,
      biological role and several molecular aspects, including cloning, heterologous
      expression and transcriptional analyses. Here we present the reconstruction of
      the fungal laccase loci evolution inferred from the comparative analysis of 48
      different sequences. The topology of the phylogenetic trees indicate that a
      single monophyletic branch exists for fungal laccases and that laccase isozyme
      genes may have evolved independently, possibly through duplication-divergence
      events. Laccases are copper-containing enzymes generally identified by the
      utilization of substituted p-diphenol substrates. Interestingly, our approach
      permitted the assignment of two copper-containing oxidases, preliminarily
      catalogued as laccases, to a different evolutionary group, distantly related to
      the main branch of bona fide laccases.

PMID- 14574107
TI  - A study on volatile organic compounds (VOCs) produced by tropical ascomycetous
      yeasts.
AB  - As a part of a program aiming at the selection of strains which might be of
      interest as sources of natural flavouring molecules, the production of volatile
      organic compounds (VOCs) by 98 ascomycetous yeast strains (representative of 40
      species belonging to 12 genera) isolated from tropical environments was
      investigated. Volatiles produced were sampled by means of headspace solid-phase
      microextraction (SPME) and the compounds were analysed and identified by gas
      chromatography-mass spectroscopy (GC-MS). The VOCs produced were found to be
      alcohols (amyl alcohol and isoamyl alcohol), aldehydes (2-methyl-2-hexenal and 2
      isopropyl-5-methyl-2-hexenal) and esters (ethyl isobutyrate, isobutyl acetate,
      isoamyl acetate, 2-methylbutyl acetate, ethyl isovalerate, isoamyl propionate and
      phenylmethyl acetate). Differences in VOC profiles were used to cluster the yeast
      strains into 25 VOC phenotypes. The different frequency of VOC phenotypes in
      three specific habitats was correlated to the divergent environmental conditions,
      possibly affecting the selection of specific yeasts. From a biotechnological
      viewpoint, this study reveals the potentiality of ascomycetous yeasts isolated
      from tropical environments as a promising source of VOCs relevant in food and
      fragrance industry.

PMID- 14574108
TI  - Molecular characterization of carotenogenic yeasts from aquatic environments in
      Patagonia, Argentina.
AB  - Fifteen aquatic environments (lakes, lagoons and rivers) of glacial origin in the
      northern Andean Patagonia (Argentina) were surveyed for the occurrence of red
      yeasts. Subsurface water samples were filtered and used for colony counting and
      yeast isolation. A preliminary quantitative analysis indicated that total yeast
      counts ranged between 0 and 250 cells l(-1). A polyphasic approach including
      physiological and molecular methods was used for the identification of 64
      carotenogenic yeast strains. The molecular characterisation of the isolates was
      based on the mini/microsatellite-primed PCR technique (MSP-PCR) employing the
      (GTG)5 and the M13 primers. Comparison of representative fingerprints of each
      group with those of the type strains of pigmented yeasts allowed the expeditious
      identification of 87.5% isolates. The sequence analysis of the D1/D2 domains of
      the 26S rDNA was employed to confirm identifications and in the characterization
      of the unidentified MSP-PCR groups. Teleomorphic yeast species were detected by
      performing sexual compatibility assays. The isolates corresponded to 6 genera and
      15 yeast species, including four new yeast species of the genera Cryptococcus
      (1), Rhodotorula (1) and Sporobolomyces (2). Rhodotorula mucilaginosa was found
      in the majority of the samples and represented ca. 50% of the total number of
      isolates. However, this yeast was not detected in aquatic environments with very
      low anthropic influence. Other frequent yeast isolates were teleomorphic yeast
      species of Rhodosporidium babjevae, R. kratochvilovae and Sporidiobolus
      salmonicolor. This study represents the first report on red yeast occurrence and
      biodiversity in northwestern Patagonia.

PMID- 14574111
TI  - Purification and biochemical characterization of a soluble alpha-glucosidase from
      the parasite Entamoeba histolytica.
AB  - A soluble alpha-glucosidase presumably involved in the general carbohydrate
      metabolism was purified from E. histolytica trophozoites by a three-step
      procedure consisting of ion exchange, size exclusion and adsorption
      chromatographies in columns of Mono Q, Sepharose CL-6B and hydroxyapatite,
      respectively. After the last step, the enzyme was enriched about 673-fold over
      the starting material with a yield of 18%. SDS-PAGE revealed the presence in the
      purified preparations of two polypeptides of comparable intensity exhibiting
      molecular weights of 43 and 68 kDa. These results and the molecular weight of 243
      kDa determined by gel filtration, suggest that the native enzyme is a
      heterotetramer consisting of two copies of each subunit. Some properties were
      investigated to determine the role of this activity in glycoprotein processing.
      Analysis of linkage specificity using a number of substrates indicated a
      preferential hydrolysis of isomaltose (alpha1,6) with much less activity on
      nigerose (alpha1,3) and maltose (alpha1,4). Trehalose (alpha1,1), kojibiose
      (alpha1,2) and cellobiose (beta1,4) were not cleaved at all. As expected,
      isomaltose competed away hydrolysis of 4-methylumbelliferyl-alpha-D-glucoside
      with a higher efficiency than nigerose and maltose. Hydrolysis of the fluorogenic
      substrate was competitively inhibited by glucose and 6-deoxy-D-glucose with
      comparable K(i) values of 0.23 and 0.22 mM, respectively. Sensitivity of the
      enzyme to the alpha-glucosidase inhibitors 1-deoxynojirimycin, castanospermine
      and australine largely depended on the substrate utilized to determine activity.
      1-Deoxynojirimycin and castanospermine inhibited isomaltose hydrolysis in a
      competitive manner with K(i) values of 1.2 and 1.5 muM, respectively. The
      properties of the purified enzyme are consistent with a general glycosidase
      probably involved in glycogen metabolism.

PMID- 14574112
TI  - Deletion of BGL2 results in an increased chitin level in the cell wall of
      Saccharomyces cerevisiae.
AB  - It is shown that the deletion of BGL2 gene leads to increase in chitin content in
      the cell wall of Saccharomyces cerevisiae. A part of the additional chitin can be
      removed from the bgl2Delta cell wall by alkali or trypsin treatment. Chitin
      synthase 1 (Chs1) activity was increased by 60 % in bgl2Delta mutant. No increase
      in chitin synthase 3 (Chs3) activity in bgl2Delta cells was observed, while they
      became more sensitive to Nikkomycin Z. The chitin level in the cell walls of a
      strain lacking both BGL2 and CHS3 genes was higher than that in chs3Delta and
      lower than that in bgl2Delta strains. Together these data indicate that the
      deletion of BGL2 results in the accumulation and abnormal incorporation of chitin
      into the cell wall of S. cerevisiae, and both Chs1 and Chs3 take part in a
      response to BGL2 deletion in S. cerevisiae cells.

PMID- 14574114
TI  - Functional characterization of genes involved in alkane oxidation by Pseudomonas
      aeruginosa.
AB  - Most clinical isolates identified as Pseudomonas aeruginosa grow on long-chain n
      alkanes, while environmental P. aeruginosa isolates often grow on medium- as well
      as long-chain n-alkanes. Heterologous expression showed that the two alkane
      hydroxylase homologs of P. aeruginosa PAO1 (AlkB1 and AlkB2) oxidize C(12)-C(16)n
      alkanes, while two rubredoxin (RubA1 and RubA2) and a rubredoxin reductase (RubB)
      homologs can replace their P. putida GPo1 counterparts in n-octane oxidation. The
      two long-chain alkane hydroxylase genes are present in all environmental and
      clinical isolates of P. aeruginosa strains tested in this study.

PMID- 14574113
TI  - Pityrialactone- a new fluorochrome from the tryptophan metabolism of Malassezia
      furfur.
AB  - As the main nitrogen source in Malassezia (M.) furfur, tryptophan induces the
      formation of fluorochromes and pigments, which makes the yeast less sensitive
      towards UV light. For the investigation of the fluorochromes, M. furfur (CBS1878)
      was incubated at 32 degrees C for 14 days on a pigment-inducing medium, and the
      agar extract was purified by column chromatography, preparative TLC and HPLC. The
      structures of the pure metabolites were determined by mass spectrometry and NMR
      spectroscopy. A pale yellow compound eluting from the column with 22%
      acetonitrile was found to exhibit a strong green-yellow fluorescence. The
      fluorochrome is a new bisindolyl compound (C(20)H(12)N(2)O(3), MW 328.33) named
      pityrialactone because of its furan-2,3-dione structure. The UV protective
      properties (lambda(max) 352, 292, 276, 224 nm) of this metabolite were confirmed
      in a yeast model. As shown by the fluorescence spectrum, pityrialactone appears
      to be responsible for the green-yellow fluorescence of pityriasis versicolor
      lesions under Wood light. Pityrialactone is accompanied by the isomeric
      bisindolylmaleic anhydride (pityriaanhydride), which has not yet been described
      as a natural product but is a known intermediate in the total synthesis of
      bisindolylmaleimides.

PMID- 14574115
TI  - Solubility enhancement of a hydrophobic flavonoid, luteolin by the complexation
      with cyclosophoraoses isolated from Rhizobium meliloti.
AB  - A plant flavone, luteolin is a well-known inducer of nod genes in the Rhizobium
      meliloti. Its poor aqueous solubility was greatly enhanced by the complexation
      with a family of cyclosophoraoses synthesized in R.meliloti. Nuclear magnetic
      resonance (NMR) spectroscopic analysis showed that the chemical shifts of the
      aromatic ring moieties of the luteolin were changed greatly by the complexation
      with cyclosophoraoses. Fourier transform infrared (FTIR) spectroscopic analysis
      also showed a restricted vibrational pattern in carbonyl stretching region of the
      luteolin due to the complexation. This effective complex formation of
      cyclosophoraoses with a plant flavone, luteolin, suggests that rhizobial
      cyclosophoraoses play an important role as a solubility enhancer of the
      hydrophobic legume-derived flavonoids.

PMID- 14574116
TI  - A new species and three new combinations in Cyphellophora, with a note on the
      taxonomic affinities of the genus, and its relation to Kumbhamaya and
      Pseudomicrodochium.
AB  - Cyphellophora guyanensis sp. nov., isolated from leaf litter in French Guyana, is
      described and illustrated. This fungus is characterized by ampulliform to flask
      shaped phialides, with a conspicuous, funnel-shaped collarette, and nearly
      straight to falcate or slightly sigmoid, (2-)3-6 septate conidia. Cyphellophora
      guyanensis is compared to the other Cyphellophora species, and the latter genus
      is compared to Kumbhamaya and Pseudomicrodochium. Kumbhamaya indica, P.
      fusarioides, and P. suttonii are transferred to Cyphellophora. The phylogenetic
      relationships of Cyphellophora with other genera of ascomycetes and related
      mitosporic fungi were inferred from the analysis of the partial nuclear ribosomal
      DNA SSU sequences data. The analysis supports a placement of Cyphellophora in
      Chaetothyriales, and probably in the Herpotrichiellaceae

PMID- 14574117
TI  - Assessment of yeast diversity in a marine environment in the south of Portugal by
      microsatellite-primed PCR.
AB  - The occurrence and diversity of yeasts in seawater was investigated in a study
      site located 20 Km off Faro, Portugal, above the Alvares Cabral Trench. A total
      of 43 water samples from different layers (above the permanent thermocline, under
      the thermocline and near the bottom) and directly from the surface, originated
      234 isolates. All the isolates were identified using a molecular approach that
      included, in a first stage, MSP-PCR fingerprinting. A total of 31 MSP-PCR classes
      were formed, 8 for the pigmented yeasts and 23 for the non-pigmented yeasts. The
      pink coloured isolates were identified by direct comparison of the new
      fingerprints with those obtained for representative strains of the various
      species. For identification of the non-pigmented yeasts, a representative isolate
      of each MSP-PCR class was selected for sequence analysis and compared with
      reference sequences. The five most abundant yeast species were Sakaguchia
      dacryoidea, Pseudozyma aphidis, Rhodosporidium babjevae, R. diobovatum and
      Debaryomyces hansenii. The distribution of isolates and species in the major
      taxonomic groups indicated that the number of basidiomycetous yeasts and their
      diversity are prevalent in relation to their ascomycetous counterpart. Diversity
      indices were determined and superficial water and water near the bottom had the
      highest diversity. The sampling effort effectiveness was estimated, and found to
      correspond to approximately 60% of the species present. MSP-PCR identification
      proved suitable for pigmented basidiomycetous yeasts and, when used in
      conjunction with sequence analysis, was effective for the characterization of non
      pigmented populations. Our results indicate that the MSP-PCR fingerprinting
      method is appropriate for the characterization of large groups of isolates due to
      its simplicity and good reproducibility.

PMID- 14574118
TI  - Cell wall composition and structure of Yarrowia lipolytica transposon mutants
      affected in calcofluor sensitivity.
AB  - A collection of transposon-mutagenized strains of Yarrowia lipolytica was
      screened for wall defects by determination of their sensitivity to calcofluor
      white. A number of strains were hypersensitive, whereas others were resistant.
      Different non-allelic mutants displayed increased sensitivity to autolysis and
      lytic enzymes, independently of whether they were sensitive or resistant to
      calcofluor white. A thorough analysis of their cell walls revealed minor
      quantitative alterations, and no significant changes in chitin content.
      Electrophoretic analysis of wall-bound and excreted proteins proved to be a
      sensitive method that revealed defects in the cell wall structure of the mutants.
      Important alterations in the patterns of the wall proteins extracted by SDS or by
      enzymatic treatments were noticed for the mutants, as compared to the parental
      strain. Mutants released to the growth medium a larger number of protein species
      than the parental strain, suggesting impairment in wall assembly of certain
      polypeptides. Patterns of wall-bound and excreted proteins, as well as
      alterations in wall chemical composition were not diagnostic of calcofluor white
      sensitivity or resistance, but were specific for each mutant. Our data show that
      an increase in either sensitivity or resistance of Y. lipolytica to certain
      levels of calcofluor is equally indicative of alterations in cell wall structure,
      independent of chitin levels.

PMID- 14574119
TI  - Influence of Al on growth, cell size and content of intracellular water of
      Arthrobacter sp. PI/1-95.
AB  - A distinct inhibition of the growth of a typical soil-born bacterium,
      Arthrobacter sp. PI/1-95, by aluminium was established. The content of
      intracellular water and (consequently) the cell size of the bacterium
      significantly increased when cells came into contact with aluminium. Both
      parameters were also increased when applying HCl, but Al caused the greater
      change, so that a distinct discrimination between the effects of aluminium on the
      one hand and a sole pH-effect on the other hand was possible. The presented
      results point to an osmo-regulative disorder connected with a malfunction of cell
      membrane and cell wall, which seems to be a probable mechanism for an Al-toxicity
      in connection with Arthrobacter sp. PI/1-95.

PMID- 14574121
TI  - Genetic selection of two new rat lines displaying different levels of anxiety
      related behaviors.
AB  - We have recently identified, using two inbred rat strains (Lewis and SHR), the
      first two loci for an emotionality-related behavior in rats (locomotion in the
      central area of the open field test). Aiming to develop an alternative genetic
      model that will help to corroborate the existence of these loci and that could
      serve as a tool in the study of anxiety, we have started breeding two new rat
      lines. From a highly heterogeneous population, we have selectively bred rats for
      four generations with high and low scores for central locomotion in the open
      field. At the fourth generation, the new outbred lines differed from each other
      for the selected trait by as much as threefold. At each generation, all rats were
      also tested in the elevated plus maze and the black and white box, with the two
      lines differing significantly also in these two models of anxiety. These results
      suggest that behavioral measures from different tests of emotionality/anxiety
      are, at least in part, genetically related. They also indicate that this newly
      developed genetic model (herein named Floripa H and L rat lines) may be useful in
      the study of anxiety, as well as serving as a tool to test the
      existence/significance of the two aforementioned loci putatively associated with
      emotionality.

PMID- 14574120
TI  - Genetic animal models for absence epilepsy: a review of the WAG/Rij strain of
      rats.
AB  - Based on the reviewed literature and the data presented in this paper,
      conclusions can be drawn with respect to the validity of the WAG/Rij strain of
      rats as a model for absence epilepsy in humans. The view that the WAG/Rij model
      has "face validity" is supported by the simultaneous presence of clinical and
      electroencephalographic signs characterizing absences in rat and humans, by the
      decrease in responsiveness during the presence of spike-wave discharges in both
      species, by the agreement between model and patient with respect to the
      preferential occurrences of spike-wave discharges at transitions in states of
      vigilance, by the corresponding modulation of spike-wave discharges by physical
      and mental activities in both and, finally, by the fact that in both humans and
      rats absence epilepsy is inherited. Against this view, however, argue two points.
      In rats, absences appear after puberty and are maintained during life, while in
      humans the seizures occur before puberty and then disappear or convert to more
      serious forms of epilepsy. The second point is the frequency difference of the
      spikes and waves in the discharge train: 8-10 Hz in the rat and 3 Hz in the human
      (though there are no a priori reasons why the frequency of spike waves in the
      burst must be the same in all species). The absence model also has predictive
      validity, based on pharmacological data that demonstrate the specificity of
      certain drugs as being effective in convulsive epilepsies and not in absence
      epilepsy. So far, all drugs affect spike-wave activity the same way in rats and
      humans, with lamotrigine being, perhaps, the only exception. Furthermore, sleep
      deprivation is a powerful provocation for the initiation of spike-wave discharges
      in both rats and humans. Potential explanations for the presence of absence
      seizures in rats have been found at the levels of activities in networks and
      nuclei; of neurons, membrane properties, and ion channels; of proteins and
      enzymes; and, finally, of genes and chromosomes. Further descriptions of the
      cellular processes can be found extensively in the literature (e.g., McCormick
      and Contreras, 2001) and those of the thalamo-cortico-thalamic network in this
      review as well as in others (Avanzini et al., 1999). Considering the extensive
      involvement of the phenomena under study with theoretical issues such as the
      relationship between sleep spindles and spike-wave discharges, and the origin of
      seizure activity, it can be concluded that the model also has construct validity
      as far as the present neurobiological theories holding for absence epilepsy in
      humans are concerned. The WAG/Rij model can therefore be recommended for
      continued use in evaluating antiepileptic drugs for monotherapy and polytherapy,
      as well as for the toxicological side effects of putative new antiabsence drugs.

PMID- 14574122
TI  - Two early studies on learning theory and genetics.
AB  - The debate between Iowa and California, Spencians and Tolmanians, over the nature
      of learning was one of the most protracted and all-involving controversies in the
      history of psychology. Spencians argued that learning consisted of stimulus
      response connections and grew incrementally; Tolmanians that it was perceptual or
      cognitive and saltatory in nature. The debate was conducted largely on the basis
      of experiments with rats, with each side finding evidence in its own laboratories
      to support its views. As the debate was winding down, two studies were carried
      out that called attention to a possible genetic basis of the great debate. The
      two schools used different strains of rat and characteristically different
      experimental situations. The two studies, however, were difficult to access at
      the time and even more so since. The present paper recalls these two studies in
      condensed form and discusses their relevance to the great debate and to selected
      current concerns.

PMID- 14574123
TI  - Selection for differences in avoidance learning: the Syracuse strains differ in
      anxiety, not learning ability.
AB  - In this review the derivation of the Syracuse (SHA/Bru and SLA/Bru) strains of
      hooded rats that were selectively bred for differences in active two-way shuttle
      box avoidance learning is described, together with a summary of the behavioral,
      hormonal, anatomical, physiological, and pharmacological characteristics that
      covary with the realized phenotypes. A selective genetic analysis is also
      described, which indicates that all of the five assessed covariates cosegregate
      with the avoidance phenotypes and are, therefore, closely linked to the high- and
      low-avoidance genotypes, which also suggests that a relatively few closely linked
      genes underlie the realized phenotypes. The low-avoidance phenotype seems best
      characterized in terms of high levels of state/trait anxiety, whereas the reverse
      is true of the high-avoidance phenotype. Anomalous endocrine data seem not to be
      consistent with the behavioral interpretation and remain to be resolved. However,
      it also seems clear that having selected for a difference in avoidance learning,
      the realized phenotypes do not involve the fundamental neurobiological substrates
      of associative or instrumental learning. Rather, differences in factors in the
      affective domain (state and/or trait anxiety) that influence performance, rather
      than learning, per se, appear to have been selected genetically.

PMID- 14574124
TI  - Zebra fish: an uncharted behavior genetic model.
AB  - The zebra fish has been a preferred subject of genetic analysis. It produces a
      large number of offspring that can be kept in small aquaria, it can be easily
      mutagenized using chemical mutagens (e.g., ethyl nitrosourea [ENU]), and high
      resolution genetic maps exist that aid identification of novel genes. Libraries
      containing large numbers of mutant fish have been generated, and the genetic
      mechanisms of the development of zebra fish, whose embryo is transparent, have
      been extensively studied. Given the extensive homology of its genome with that of
      other vertebrate species including our own and given the available genetic tools,
      zebra fish has become a popular model organism. Despite this popularity, however,
      surprisingly little is known about its behavior. It is argued that behavioral
      analysis is a powerful tool with which the function of the brain may be studied,
      and the zebra fish will represent an excellent subject of such analysis. The
      present paper is a proof of concept study that uses pharmacological manipulation
      (exposure to alcohol) to show that the zebra fish is amenable to the behavioral
      genetic analysis of aggression and thus may allow us to reveal molecular
      mechanisms of this behavioral phenomenon relevant to vertebrates.

PMID- 14574125
TI  - Behavior genetics of canine aggression: behavioral phenotyping of golden
      retrievers by means of an aggression test.
AB  - Molecular genetic analysis of complex traits such as aggression strongly depends
      on careful phenotyping of individuals. When studying canine aggression, the
      information provided by the owners of the dogs is often not detailed and reliable
      enough for this purpose. Therefore we subjected 83 golden retrievers, both
      aggressive and nonaggressive individuals, to a behavioral test. These tests were
      analyzed with help of an ethogram, resulting in a behavioral profile for each of
      the dogs. In this article three methods are described of converting these
      profiles into a measure of behavioral phenotype. The usefulness of the methods is
      evaluated by comparing the test results with information provided by owners.
      Moreover, the hypothesis underlying all these methods, that a lowered threshold
      for aggressive behavior in general is present in the dogs, is also evaluated.
      Future research will need to reveal whether the methods meet the high standards
      that are necessary for studying complex traits.

PMID- 14574126
TI  - Individual variation in aggression of feral rodent strains: a standard for the
      genetics of aggression and violence?
AB  - This article summarizes the broad individual differences in aggressiveness and
      its relationship with several other behavioral, physiological, and
      neurobiological characteristics that exist in an outbred laboratory strain of
      male feral rats. Based on the observations that the individual level of offensive
      aggressive behavior (i.e., the tendency to defend the home territory) is strongly
      related to the way they react to various other environmental challenges, it is
      argued that the individual's level of offensiveness is an important indicator and
      component of a more traitlike behavioral physiological response pattern (coping
      strategy) to environmental demands. The coping style of aggressive animals is
      principally aimed at a (pro)active prevention or manipulation of a stressor,
      whereas the nonaggressive individuals tend to passively accept or react to it.
      The (pro)active and reactive/passive behavioral coping styles are clearly
      associated with distinct patterns of autonomic/endocrine (re)activity and
      underlying neurobiological correlates and determinants. Consequently, these
      individual differences in aggression/coping style may not only determine the
      individual vulnerability to stress-related disease, and hence be an important
      factor in the population dynamics of the species, but may also determine
      responsivity to pharmacotherapeutic treatments. From an animal modeling point of
      view, it is argued that the aggressive extremes of this variation may, under the
      proper testing conditions, have an enhanced propensity to develop pathological
      forms of aggression and/or coping, for example, antisocial traits, violence, or
      impulsivity disorders. Finally, it is proposed that the use of these feral
      animals as base "material" for genetic association (i.e., QTL search, mRNA
      differential expression, nucleic acid microarray analysis) and manipulation
      (i.e., gene silencing or amplification by antisense ODN, siRNA, and/or viral gene
      transfer methodologies) studies would most likely be the best option for
      dissecting successfully the genetic basis of both normal and pathological forms
      of aggression and/or coping.

PMID- 14574127
TI  - Anxiety profiles of mice selectively bred for intermale aggression.
AB  - In the present study we compared genetically selected aggressive (TA) and
      nonaggressive (TNA) male mice, as well as males from an unselected control line
      (SW), in three tests of anxiety: the elevated plus-maze, the light-dark box, and
      the staircase test. Males were tested repeatedly for 3 days. In all three tests
      TA males were found to be more active and less anxious than TNA males, with SW
      males showing more or less intermediate scores. Furthermore, repeated plus-maze
      testing induced anxiety-like behavior in both TA and TNA mice, whereas repeated
      testing in the light-dark and staircase paradigms resulted in different
      responses. Whereas TNA animals were found to be stable, TA animals showed
      habituation on the second and third day of testing. The obtained data support the
      conclusion that a higher-level offensive aggression entails lower level of
      anxiety.

PMID- 14574128
TI  - Agonistic behavior and unpredictable chronic mild stress in mice.
AB  - A significant proportion of patients suffering from major clinical depression
      exhibit sudden bursts of anger often described as "panic attacks without anxiety
      or fear" or "irritability." We investigated aggressive behavior in mice from four
      different inbred strains subjected to unpredictable chronic mild stress (UCMS).
      Our results show that UCMS affects self-grooming behavior, as evaluated by the
      state of an animal's fur, with severity of symptoms differing according to
      genetic background. Furthermore, UCMS increased aggression both in a resident
      intruder test and between cage-mates. UCMS is therefore a valuable model of the
      problematic aggressive behavior seen in depressive patients.

PMID- 14574129
TI  - Sexual aggression in mice: effects of male strain and of female estrous state.
AB  - We have observed that 50% of FVB/NtacfBR ("FVB") males were aggressive toward
      females in tests of mating behavior. We decided to gather basic evidence for an
      effect of genotype on this behavior by testing for strain differences between FVB
      and C57BL/6J ("B6") male mice. Also, hypotheses developed from theoretical work
      on sexually coercive behavior suggest there should be a cycling effect on
      sexually aggressive behavior (Smuts and Smuts, 1993). We tested for an estrous
      cycling effect by using stimulus females in a state of either estrus or diestrus.
      Both strains modulated mating behavior to female cycling state. Cycling state did
      not modulate B6 aggression. FVB males were more aggressive than B6 males, and
      cycling state modulated their behavior. We conclude that sexually aggressive male
      mice modulate aggressive behavior to female social signals and indicate how this
      data can be used to study the genetics of sexual aggression.

PMID- 14574130
TI  - Aggression and the three opioid families (endorphins, enkephalins, and
      dynorphins) in mice.
AB  - Previous studies suggest that brain opioid activity decreases aggression in
      animal models. The main objective of the current study was to examine the
      possible genetic relationship between intermale aggression and brain levels of
      enkephalins, endorphins, and dynorphins in 11 inbred strains of mice. Pursuit,
      rattling, and attack behaviors were observed in a dyadic encounter with a
      standard opponent. It appeared that, as expected, enkephalins and endorphins were
      always negatively correlated with aggression scores. The findings indicate that
      brain Met5-enkephalin levels were significantly and highly positively correlated
      with attack latency. Brain adrenocorticotrophic hormone (ACTH) and beta-endorphin
      levels were significantly and negatively correlated with the number of rattlings,
      which is consistent with the hypothesis that rattling is a stress-related
      behavior. In contrast with Met5-enkephalin, ACTH and beta-endorphin, the
      correlations between dynorphin A and aggression scores were nonsignificant and
      very low. These preliminary results suggest that common genetic sources of
      variation contribute to differences between the 11 inbred strains in both
      endogenous opioidergic systems and intermale aggression. Further studies are
      required to confirm the genetic relationship between offensive aggression and
      brain enkephalins and endorphins and to better understand the mechanisms
      underlying the role of endogenous opioids in offensive aggression with regard to
      opioid receptor activity.

PMID- 14574131
TI  - Large-scale gene expression profiling of discrete brain regions: potential,
      limitations, and application in genetics of aggressive behavior.
AB  - Many behavioral geneticists are interested in unraveling the molecular mechanisms
      underlying aggressive behavior. So far, most scientists have based their search
      for aggression-related genes on a preliminary functional hypothesis. Large-scale
      gene expression profiling techniques, such as serial analysis of gene expression
      (SAGE) and DNA microarrays, now enable the screening of expression levels of
      thousands of genes simultaneously, allowing the identification of new candidate
      aggression-related genes expressed in brain and thus the generation of new
      hypotheses. However, expression profiling in the brain is challenging, as brain
      is a complex heterogeneous tissue where large numbers of genes are expressed and
      relatively small changes in gene expression occur. In this special issue, we
      focus on the principles of SAGE and DNA microarrays, as well as their advantages
      and disadvantages and application to analysis in brain tissue in order to
      identify aggression-related genes.

PMID- 14574132
TI  - From transcriptional regulation to aggressive behavior.
AB  - Gene expression in higher organisms, is, to a large degree, controlled at the
      level of transcription, where DNA-binding proteins (transcription factors) play
      an influential role in gene regulation. This is achieved through various
      mechanisms, including those that involve silencer and enhancer regions. Variation
      in those regulatory regions, as well as in the genes encoding the transcription
      factors, has been shown to generate functional effects at the molecular,
      cellular, and neurobehavioral levels. The aim of the present paper is two-fold.
      First, for the sake of clarity and to reintroduce the terminology to Behavior
      Genetics readers, we review the concepts of gene structure, gene expression, and
      gene regulation. Second, using distinct bioinformatic tools, we set out to
      identify transcription factors that could be involved in the transcriptional
      regulation of genes known to be associated with aggressive behavior in mice. The
      results of this in silico study reveal common putative transcription factor
      binding sites among the set of genes investigated (especially for SRY),
      suggesting similar molecular transcriptional mechanisms.

PMID- 14574133
TI  - Toward an animal model for antisocial behavior: parallels between mice and
      humans.
AB  - The goal of this article is to examine whether mouse lines genetically selected
      for short and long attack latencies are good animal models for antisocial
      behavior in humans. To this end, we compared male Short and Long Attack Latency
      mice (SAL and LAL, respectively) with the extremes of the Dunedin
      Multidisciplinary Health and Development Study (men who persistently displayed
      antisocial behavior [Persisters] and men who never manifested antisocial behavior
      [Abstainers]). Groups were compared on the basis of five distinct domains:
      aggression/violence, reproduction, cognition, behavioral disorders, and
      endophenotypes. Our observations point to considerable parallels between, on one
      side, SAL and Persisters, and, on the other side, between LAL and Abstainers (but
      to a lesser extent). We believe that SAL and LAL are good mouse models to study
      the development of antisocial behavior and will yield valuable and testable
      hypotheses with regard to the neurobiological and genetical architecture of
      antisocial behavior.

PMID- 14574134
TI  - Individual differences in aggression: genetic analyses by age, gender, and
      informant in 3-, 7-, and 10-year-old Dutch twins.
AB  - Aggression in humans is associated with substantial morbidity and mortality. In
      this study we report on the aggressive behavior syndrome (AGG) in young children
      as defined by the Child Behavior Checklist (CBCL) and the Teacher Report Form
      (TRF). We assessed aggression in a large sample of Dutch twins at ages 3, 7, and
      10 years. The purpose of this study was three-fold. First, we determined the
      number of children who are "clinically deviant" on the AGG scale. Second, we
      assessed the genetic and environmental contributions to AGG for the maternal,
      paternal, and teacher ratings at each age, for boys and girls. Third, we explored
      issues of rater bias by analyzing parental and teacher data simultaneously. CBCL
      data were available from mothers on 6436 three-year-old, 5451 seven-year-old, and
      2972 ten-year-old twin pairs and CBCL data from fathers on 4207 three-year-old,
      4269 seven-year-old, and 2295 ten-year-old twin pairs. Teacher report data from
      the TRF were collected for 1036 seven-year-old and 903 ten-year-old twin pairs
      from the Netherlands Twin Registry. Structural equation modeling was employed to
      obtain genetic and environmental estimates at each age. Analyses were conducted
      separately by age and informant, as well as simultaneously, for all informants.
      Differences in raw scores across gender were found, with boys being rated as more
      aggressive than girls by all informants. Mothers reported more symptoms than
      fathers, who reported more symptoms than teachers. Evidence for moderate to high
      genetic influence (51%-72%) was seen for AGG by all three informants at all ages
      with only small sex differences in heritability estimates. Best fitting models
      for AGG by parent reports also included a small contribution of common
      environment. The largest sex differences in heritabilities were seen at age 10.
      Contributions of common (13%-27%) and unique (16%-31%) environment were small to
      moderate. There was some evidence of genetic dominance by teacher report for 10
      year-old girls.

PMID- 14574135
TI  - Causes of stability of aggression from early childhood to adolescence: a
      longitudinal genetic analysis in Dutch twins.
AB  - This study investigated the contribution of genetic and environmental influences
      on the stability of aggressive behavior from early childhood to adolescence. Two
      developmental models, the simplex model and the common factor model, were tested
      to study the underlying processes of stability and change. Measures of aggressive
      behavior (AGG) were obtained from maternal CBCL data as part of a large ongoing
      longitudinal study of the Netherlands Twin Registers (NTR) and included data from
      6488 three-year-old twin pairs, 5475 seven-year-old twin pairs, 2983 ten-year-old
      twin pairs, and 1509 twelve-year-old twin pairs. AGG showed moderate to high
      stability during childhood. The stability coefficients ranged from 0.41 to 0.77
      across varying intervals. Averaged across boys and girls, genetic factors
      accounted for approximately 65% of the total stability. Longitudinal genetic
      analysis indicated a simplex model for genetic effects, which suggests a dynamic
      development process consisting of transmission of existing genetic effects
      interacting with new genetic influences. This is especially true at age 7, when
      the influence of new genetic factors was large. Shared environmental factors
      accounted for approximately 25% of phenotypic stability, and it seemed that a
      stable set of the same shared environmental factors underlay the development of
      AGG. Nonshared environmental factors, when important, are age specific. Sex
      specific differences for stability were identified. For boys, genetic influences
      were greater, whereas for girls shared environmental factors were more important.
      These data support the idea that both genetic and environmental influences play a
      role in the stability of AGG from age 3 to 12.

PMID- 14574136
TI  - Co-occurrence of aggressive behavior and rule-breaking behavior at age 12: multi
      rater analyses.
AB  - Aggressive Behavior (AGG) and Rule-Breaking Behavior (RB) are two of the eight
      CBCL syndromes. The phenotypic correlation between AGG and RB ranges from.48
      to.76, and varies depending on the rater and the sex of the child. Prevalence of
      AGG and RB (i.e., T > or = 67) is in the range of 6%-7% in both boys and girls.
      Fifty percent to 60% of the children who are deviant on AGG are also deviant on
      RB and vice versa. Why so many children show problem behavior in the clinical
      range for both syndromes is unclear. This co-occurrence could be due to genetic
      factors influencing both traits, to environmental factors influencing both
      traits, or to both. The purpose of this study is to use a genetically informative
      sample to estimate genetic and environmental influences on AGG and RB and to
      investigate the etiology of the co-occurrence of both behaviors. We do this using
      multiple informants to take into account underlying sources of parental agreement
      and disagreement in ratings of their offspring. To this end, mother and father
      ratings of AGG and RB were collected by using the Child Behavior Checklist in a
      large sample of 12-year-old twins. Parental agreement is represented by an
      interparent correlation in the range of .53-.76, depending on phenotype (AGG or
      RB) and sex of the child. Genetic influences account for 79% and 69% of the
      individual differences in RB and AGG behavior (defined as AGG and RB on which
      both parents do agree) in boys. In girls 56% and 72% of the variance in RB and
      AGG are accounted for by genetic factors. Shared environmental influences are
      significant for RB in girls only, explaining 23% of the total variance. Eighty
      percent of the covariance between AGG and RB, similarly assessed by both parents,
      can be explained by genetic influences. So, co-occurrence in AGG and RB is mainly
      caused by a common set of genes. Parental disagreement seems to be a combination
      of so-called rater bias and of parental specific views.

PMID- 14574137
TI  - A twin study of differentiation of cognitive abilities in childhood.
AB  - The differentiation hypothesis in cognitive development states that cognitive
      abilities become progressively more independent as children grow older. Studies
      of phenotypic development in children have generally failed to produce convincing
      support for this hypothesis. The aim of the present study is to investigate the
      issue of differentiation at the genetic and environmental level. Six psychometric
      measures assessing verbal and nonverbal cognitive abilities were administered to
      209 Dutch twin pairs at ages 5, 7, and 10 years. Longitudinal results provided
      little evidence for the differentiation hypothesis. Stability in subtest
      performance is due mainly to genetic influences. The shared environment
      contribution to phenotypic stability is small. The unique environment contributes
      to age-specific variance only.

PMID- 14574138
TI  - Direction of causation modeling between cross-sectional measures of parenting and
      psychological distress in female twins.
AB  - Under certain conditions, cross-sectional analysis of cross-twin intertrait
      correlations can provide important information about the direction of causation
      (DOC) between two variables. A community-based sample of Australian female twins
      aged 18 to 45 years was mailed an extensive Health and Lifestyle Questionnaire
      (HLQ) that covered a wide range of personality and behavioral measures. Included
      were self-report measures of recent psychological distress and perceived
      childhood environment (PBI). Factor analysis of the PBI yielded three
      interpretable dimensions: Coldness, Overprotection, and Autonomy. Univariate
      analysis revealed that parental Overprotection and Autonomy were best explained
      by additive genetic, shared, and nonshared environmental effects (ACE), whereas
      the best-fitting model for PBI Coldness and the three measures of psychological
      distress (Depression, Phobic Anxiety, and Somatic Distress) included only
      additive genetic and nonshared environmental effects (AE). A common pathway model
      best explained the covariation between (1) the three PBI dimensions and (2) the
      three measures of psychological distress. DOC modeling between latent constructs
      of parenting and psychological distress revealed that a model which specified
      recollected parental behavior as the cause of psychological distress provided a
      better fit than a model which specified psychological distress as the cause of
      recollected parental behavior. Power analyses and limitations of the findings are
      discussed.

PMID- 14574139
TI  - Remembered parental bonding in adult twins: genetic and environmental influences.
AB  - One common assumption in psychology is the impact of parenting and parent-child
      relationships on the child's adjustment throughout the life span. Studies have
      indicated that there are genetic influences on memories of parenting, but how
      these influences are mediated has not typically been investigated. A sample of
      150 pairs of monozygotic and 176 pairs of dizygotic Swedish twin women reported
      on personal characteristics and on remembered relationships with their mother and
      father using the Parental Bonding Instrument (PBI). Quantitative genetic analyses
      showed moderate genetic influences for remembered parental warmth, which also was
      partly explained by genetic influences for optimism, aggression, and humor. The
      other two PBI scales, authoritarianism and protectiveness, showed only shared and
      nonshared environmental influences. One interpretation of the findings is that
      heritable personal characteristics of children elicit parental warmth. However,
      other explanations such as personality characteristics influencing how
      experiences with parents are interpreted or circumstances in adult life that
      affect the recall of experiences could not be ruled out.

PMID- 14574140
TI  - Using shared and unique parental views to study the etiology of 7-year-old twins'
      internalizing and externalizing problems.
AB  - In a sample of 1,940 Dutch 7-year-old twin pairs we studied the etiology of
      individual differences in Internalizing and Externalizing behavioral problems.
      For the majority of twins in the sample, both maternal and paternal ratings of
      behavioral problems were obtained from the Child Behavior Checklist. This made it
      possible to take into account processes underlying agreement and disagreement
      between maternal and paternal ratings. For both problem behaviors, a Psychometric
      model fitted the data better than a Rater Bias model, implying that parents, in
      addition to the behaviors they similarly observed, also assessed unique aspects
      of their children's behaviors. Relatively large genetic influences were found for
      Externalizing problems, explaining over 50% of the variance in both boys and
      girls. For internalizing problems, the heritability was over 30% in both sexes.
      Shared environmental factors were nearly as important as genetic influences in
      explaining the variation in behavioral problems. For both Externalizing and
      Internalizing problems, around 30% of the variance was accounted for by the
      shared environmental factors.

PMID- 14574141
TI  - Heritability of daytime cortisol levels in children.
AB  - Individual differences in the level of the stress hormone cortisol play a
      prominent role as an explanatory variable in studies on psychopathology.
      Relatively few studies have paid attention to individual differences in cortisol
      levels and the etiology of these differences, in particular their possible
      genetic basis. All these studies have been in adults. The aim of this study was
      to estimate genetic and environmental influences on basal cortisol levels in 12
      year-old children. To this end, four samples of salivary cortisol were collected
      on two consecutive days in a sample of 180 twin pairs. Low correlations were
      found between cortisol levels at different points in time during the day. A
      significant genetic contribution was found to the variation of basal cortisol
      levels in the morning and afternoon samples, but not in the evening sample.
      Heritability did not differ for boys and girls and was highest (60%) for cortisol
      levels during the sample taken about 45 minutes after awakening. This cortisol
      awakening response provides a useful endophenotype in the search for genes that
      may affect hypothalamic-pituitary adrenocortical functioning in children.

PMID- 14574142
TI  - Chromosomal NOR activity in mice selected for high and low swim stress-induced
      analgesia.
AB  - Metaphase nucleolar organizer region (NOR) activity was studied in mouse lines
      selectively bred for high analgesia (HA) and for low analgesia (LA) induced by 3
      min swimming in 20 degrees C water. Apart from pain-related traits, HA mice also
      manifest, as compared to the LA line, higher emotionality in certain behavioral
      tests and are less capable of coping with the hypothermic challenge of swimming
      in cold water, in addition to being more susceptible to the mutagenic effect of
      whole-body gamma-radiation and mitomycin C injection. We here compared NOR
      activity in HA and LA mice. A statistically significant difference (p < or =.01)
      was detected in mean silver-stained nucleolar number/cell between the HA and LA
      lines, being lower for HA mice. We propose that the breeding strategy, along with
      the differentiation of stress-related phenomena, has altered the activity of
      genes coding rRNA and that this activity is important in controlling DNA repair
      in each line. It is concluded that quantitative studies of nucleolar changes may
      be useful in evaluating the biological reactivity to stress stimuli.

PMID- 14574143
TI  - Fitting genetic models to twin data with binary and ordered categorical
      responses: a comparison of structural equation modelling and Bayesian
      hierarchical models.
AB  - We compare Bayesian methodology utilizing free-ware BUGS (Bayesian Inference
      Using Gibbs Sampling) with the traditional structural equation modelling approach
      based on another free-ware package, Mx. Dichotomous and ordinal (three category)
      twin data were simulated according to different additive genetic and common
      environment models for phenotypic variation. Practical issues are discussed in
      using Gibbs sampling as implemented by BUGS to fit subject-specific Bayesian
      generalized linear models, where the components of variation may be estimated
      directly. The simulation study (based on 2000 twin pairs) indicated that there is
      a consistent advantage in using the Bayesian method to detect a "correct" model
      under certain specifications of additive genetics and common environmental
      effects. For binary data, both methods had difficulty in detecting the correct
      model when the additive genetic effect was low (between 10 and 20%) or of
      moderate range (between 20 and 40%). Furthermore, neither method could adequately
      detect a correct model that included a modest common environmental effect (20%)
      even when the additive genetic effect was large (50%). Power was significantly
      improved with ordinal data for most scenarios, except for the case of low
      heritability under a true ACE model. We illustrate and compare both methods using
      data from 1239 twin pairs over the age of 50 years, who were registered with the
      Australian National Health and Medical Research Council Twin Registry (ATR) and
      presented symptoms associated with osteoarthritis occurring in joints of the
      hand.

PMID- 14574144
TI  - The heritability of depression symptoms in elderly Danish twins: occasion
      specific versus general effects.
AB  - Depression symptomatology was assessed up to four times at 2-year intervals on a
      sample of 2100 Danish twins initially aged 70 years and older. Data were analyzed
      using the biometric growth model approach proposed by Neale and McArdle (2000).
      Results show that occasion-specific depression is moderately and equally
      heritable in men and women (occasion-specific estimates of heritability ranged
      from 22% to 37%). Estimates of phenotypic variance, genetic variance, and
      heritability did not vary systematically across waves. In the best-fitting growth
      model, depression symptomatology was accounted for by two factors: (1) a level
      (i.e., average) effect that was highly heritable (estimate of 69% in women and
      64% in men) and reflected overall vulnerability, and (2) a residual effect that
      was nonheritable and reflected occasion-specific circumstances that could either
      exacerbate or moderate inherited vulnerability. Attempts to identify specific
      genetic contributions to depression might profitably focus on average levels
      across multiple assessments, while attempts to identify specific environmental
      effects might profitably focus on deviations about this average.

PMID- 14574145
TI  - Sex differences in genetic risk for dementia.
AB  - We used two Swedish twin samples to test whether women are at greater risk than
      men of developing dementia and whether there are sex differences in mechanisms
      underlying dementia and cognitive dysfunction. Dementia analyses found no sex
      differences in incidence of dementia or Alzheimer's disease among initially
      intact participants followed longitudinally. Twin analyses indicated a
      substantial genetic influence on liability to incident dementia. Although sex
      differences in model parameters were not statistically significant, for women but
      not men an equally attractive model included genetic influence due to both
      additive effects and dominance or epistasis. In the cognitive dysfunction
      analyses, results from a sex limitation model raise the possibility that either
      different genes or different environments have a role for men and women. We
      conclude that women are not at higher risk of developing dementia, but there is a
      hint that different genetic processes may be involved for women than for men.

PMID- 14574146
TI  - Genetic and environmental influences on decline in biobehavioral markers of
      aging.
AB  - Latent growth models were applied to longitudinal twin data on markers of aging
      to investigate genetic and environmental influences on the processes of change
      with age. The sample included 1957 participants aged 50 to 96 years. Five markers
      were assessed: forced expiratory volume, mean arterial pressure, grip strength,
      motor functioning, and well-being. Data were gathered at up to three follow-up
      occasions at intervals of 3 years. Results indicated monotonic changes with age
      for all but two variables. Performance on motor functioning and well-being was
      stable until age 65 or 70, followed by significant decline. Genetic influences on
      the level of performance were indicated for all five markers of aging. Genetic
      influences on the slope were found for only three of the variables: motor
      functioning, mean arterial pressure, and forced expiratory volume. Investigations
      of the aging process will differ depending on whether the focus is on static
      performance or change.

PMID- 14574147
TI  - Age trajectories of genetic variance in physical functioning: a longitudinal
      study of Danish twins aged 70 years and older.
AB  - Genetic-evolutionary theories of aging predict that the genetic variance for
      fitness traits increases with age, while epidemiological-gerontological theories
      predict an increase in the environmental variance for most traits. In this study
      we examine the age trajectories of the genetic and environmental variance in
      physical functioning in a sample of 4731 Danish twins aged 70+ who are being
      followed longitudinally every second year with up to four assessments completed.
      A biometric growth model (Neale and McArdle, 2000) was applied to a validated
      physical ability score. The model included an overall level effect, a rate of
      linear change effect, and residual effects. The best-fitting model was a sex
      specific model including additive genetic and nonshared environmental factors
      affecting level and rate of change and only nonshared environmental factors
      affecting the wave-specific levels. For both sexes there is an approximate
      doubling of both the total variance and the genetic variance in the physical
      ability score over the four waves and, hence, a rather stable heritability.
      However, the heritability is approximately.10 for males and.30 for females in all
      four waves. The heritability of level and slope showed a similar pattern:.11-14
      in males and.35-.39 in females. The increase in both additive genetic variance
      and environmental variance is in agreement with genetic-evolutionary and
      epidemiological-gerontological theories of aging, respectively. The present study
      suggests that overall level of strength may be a better phenotype for future
      molecular genetic studies on physical functioning in the elderly than rate of
      change, because rate of change is vulnerable to sample attrition due to mortality
      and dropout and because four waves were needed to be able to detect a
      heritability for rate of change of the same magnitude as the heritability for
      level of physical functioning.

PMID- 14574148
TI  - Structural equation models for evaluating dynamic concepts within longitudinal
      twin analyses.
AB  - A great deal of prior research using structural equation models has focused on
      longitudinal analyses and biometric analyses. Some of this research has even
      considered the simultaneous analysis of both kinds of analytic problems. The key
      benefits of these kinds of analyses come from the estimation of novel parameters,
      such as the heritability of changes. This paper discusses some recent extensions
      of longitudinal multivariate models that can be informative within biometric
      designs. In the methods section we review a previous latent growth structural
      equation analysis of the New York Twin (NYT) longitudinal data (from McArdle et
      al., 1998). In the models section we recast this growth model in terms of latent
      difference scores, add several new dynamic components, including coupling
      parameters, and consider biometric components and examine model stability. In the
      results section we present new univariate and bivariate dynamic estimates and
      tests of various dynamic hypotheses for the NYT data, and we consider a few ways
      to interpret the age-related biometric components of these models. In the
      discussion we consider our limitations and present suggestions for future dynamic
      genetic research.

PMID- 14574149
TI  - The influence of mortality on twin models of change: addressing missingness
      through multiple imputation.
AB  - Twin analyses of phenotypes that are associated with mortality may provide biased
      heritability estimates if the models require that data from both members of a
      pair are available. This is particularly true when longitudinal analyses are
      applied to measures of cognition or biomarkers of aging. The effect of applying
      imputational techniques that include information on age at death was tested on
      longitudinal data from two twin studies of aging, each with up to four occasions
      of measurement. Measures of twin similarity for intercepts and slopes from three
      latent growth curve models were compared: without imputed data, including imputed
      data but without information on age at death, and including imputed data with
      information on age at death. Results indicated that twin similarity for slopes
      decreases when mortality is accounted for, but that considerable age-related
      covariation remains.

PMID- 14574150
TI  - Investigating age differences in the genetic and environmental structure of the
      tridimensional personality questionnaire in later adulthood.
AB  - In this study we examined cross-sectional age differences in means, phenotypic
      covariance structure, and the underlying genetic and environmental structure of
      four personality constructs from Cloninger's personality system: Novelty Seeking
      (NS), Harm Avoidance (HA), Reward Dependence (RD), and Persistence (PS). Study
      participants were same-sex female twins between the ages of 50 and 96, drawn from
      the American Association of Retired Persons (AARP) twin sample. We examined age
      differences by comparing younger (age 50-65) and older (age 661) cohorts (based
      on a median split of the sample) and by estimating biometrical model parameters
      as linear and quadratic functions of continuous age. Results indicated modest,
      but significant, mean-level declines across this age range for NS, RD, and PS. HA
      showed no significant mean differences. We found moderate heritability estimates
      for all of the TPQ higher-order personality dimensions, ranging from 0.16 to
      0.62. No significant age differences in the proportion of genetic and
      environmental influences on the TPQ dimensions were found. For HA, RD, and PS
      there were no significant age-related differences in total variance. However, for
      NS we observed a decline in total phenotypic variance across age cohorts.

PMID- 14574151
TI  - A novel mouse-friendly cognitive task suitable for use in aging studies.
AB  - Tests of cognition in mice frequently employ deprivations or aversive stimuli to
      motivate learning. Such manipulations may confound interpretation of differences
      in performance. Concerns arising from the potential confounding are accentuated
      when the object of the experiment is to compare cognitive function of young and
      old animals because aging alters many processes that affect maze performance. To
      assuage some of these concerns, we tested the potential of a novel reward
      procedure to motivate maze learning. Food-and water-satiated mice of two
      genetically heterogeneous groups that gained access to their home cage after
      reaching the goal box of a Lashley III maze attained the acquisition criterion as
      quickly as did mice motivated by hunger and given food reward. We suggest that
      "return to home cage" is a useful reinforcer in tests of cognition. This reward
      procedure is unusual in that it offers an important animal-friendly alternative
      to the usual ways of motivating cognitive performance, is economical of
      experimenter time, and may avoid the potentially confounding effects of
      physiological deprivations and aversive stimuli on maze performance of aged mice.

PMID- 14574152
TI  - Mate choice, sexual conflict, and evolution of senescence.
AB  - Sex-related differences in longevity are common throughout the animal kingdom.
      Previous studies have suggested that at least part of these differences may be
      due to sex-specific costs of reproduction. Recently, workers have recognized that
      sexual conflicts of interest between males and females may play a significant
      role in the evolution of sexually dimorphic traits. Here I explore the
      possibility that sexual conflict may explain sex-specific differences in
      longevity and may act as a driving force in the evolution of senescence. I
      present comparative evidence for this hypothesis and discuss the potential
      relevance of sexual conflict theory to the search for specific genes that
      influence longevity. One implication of a sexual conflict theory of aging is that
      genes that influence senescence, and in particular those that affect sex
      differences in aging, may evolve very rapidly and so be difficult to detect.

PMID- 14574153
TI  - Origins of the Leeds Castle Polyposis Group.

PMID- 14574154
TI  - History of the International Collaborative Group on Hereditary Non Polyposis
      Colorectal Cancer.

PMID- 14574155
TI  - Histopathological characteristics of BRCA1- and BRCA2-associated intraperitoneal
      cancer: a clinic-based study.
AB  - The aim of the research was to assess possible histopathological differences
      between BRCA1- and BRCA2-associated malignant intraperitoneal (ovarian/fallopian
      tube/peritoneal) tumors and their sporadic counterparts. Dutch families harboring
      pathogenic BRCA1 or BRCA2 mutations were selected. Included were patients who had
      had malignant primary ovarian, fallopian tube or peritoneal tumors.
      Histopathological data was compared with data obtained from the Dutch cancer
      registry between 1989 and 1993 (reference group). A total of 63 with primary
      intraperitoneal malignant tumors were identified in 41 families. Non-epithelial
      malignant tumors were not observed in the study group versus 6% (n = 404) in the
      reference group (n = 6789, P = 0.04). These tumors were excluded from further
      analysis, as were ovarian adenocarcinomas not otherwise specified, since these
      were detected in 22% of the study group, and in 19% of the reference group (P =
      0.76). Serous carcinomas were detected in 94% (47/50) of the women in the study
      group in contrast to 62% (3145/5088) of the reference group (P < 0.01). In the
      study group, mucinous and endometrioid ovarian adenocarcinomas and serous ovarian
      borderline tumors each comprised 2.0% of the tumors. Clear cell ovarian
      carcinomas were not detected. In contrast, these percentages were 16% (P < 0.01),
      10% (P = 0.07), 7% (P = 0.16) and 5% (P = 0.12), respectively, in the reference
      group. In the study group, 6.0% of the carcinomas arose in the fallopian tube
      versus 1.9% in the reference group (P = 0.03). Four percent of the study group
      developed primary serous peritoneal carcinomas, versus six percent in the
      reference group (P = 0.57). Serous carcinoma is the predominant type of
      intraperitoneal malignancy occurring in women harboring BRCA1 or BRCA2 mutations.
      Non-epithelial cancer does not seem to be part of the tumor spectrum of BRCA
      mutation carriers. This suggests, therefore, that serous tumors may be the only
      subtype related to a BRCA1 or BRCA2 mutation. Furthermore, fallopian tube
      carcinoma occurred more often in BRCA mutation carriers than in the reference
      population.

PMID- 14574156
TI  - Bannayan-Riley-Ruvalcaba syndrome: further delineation of the phenotype and
      management of PTEN mutation-positive cases.
AB  - Bannayan-Riley-Ruvalcaba syndrome (BRRS) is characterised by macrocephaly,
      intestinal hamartomatous polyps, lipomas, pigmented maculae of the glans penis,
      developmental delay and mental retardation. The syndrome follows an autosomal
      dominant pattern of inheritance. In 1997 reports on two BRRS patients with a
      deletion at 10q23.2-q24.1 were published. In the same year, the first two
      families with BRRS and a mutation of the PTEN gene were reported. Mutations in
      the PTEN gene have also been demonstrated in patients with Cowden syndrome (CS),
      which shows partial clinical overlap with BRRS, and in families with cases both
      of BRRS and CS. PTEN mutation positive BRRS and CS are likely to be different
      phenotypic presentations of the same syndrome. If BRRS and CS are one single
      condition, the question arises whether patients with BRRS should be screened for
      malignant tumours, since patients with Cowden syndrome have an increased risk of
      breast, endometrial, thyroid and renal cancer. We present two isolated cases and
      one family and confirm that BRRS and CS are allelic. Furthermore, we review the
      PTEN mutation positive BRRS cases, to further delineate the phenotype and to
      compare the cases with a genomic deletion with the cases with a point mutation.
      We recommend offering BRRS cases with a mutation in PTEN the same surveillance
      protocol for (malignant) tumours as is currently recommended for CS. In addition,
      we propose a yearly haemoglobin test from early infancy for the early detection
      of intestinal hamartomas, which are likely to give severe complications,
      especially in BRRS cases.

PMID- 14574157
TI  - Family history of colorectal cancer in a Sweden county.
AB  - Hereditary nonpolyposis colorectal cancer (HNPCC) and familial adenomatosis
      polyposis (FAP) are well-known high-risk cancer syndromes. Hereditary colorectal
      cancer (HCRC) with at least three relatives with colorectal cancer and a dominant
      pattern of inheritance but with no specifications for age at onset and two close
      relatives with colorectal cancer (TCR) are other forms of familial clustering
      known to carry an increased risk of the disease. The frequency of the total
      burden of familial colorectal cancer is not well known. We therefore investigated
      the family history of 400/411 (97%) eligible patients with recently diagnosed
      colorectal cancer in Vastmanland county, Sweden, during a 3-year period. Records
      or death certificates confirmed the diagnoses of relatives. Five patients (1.2%,
      95% CI 0.15-2.2) were diagnosed as having HNPCC, eight (1.9%, 95% CI 0.6-3.2) as
      having HCRC and thirty-four (8.3%, 95% CI 5.6-11.0) were identified as having
      TCR. In total, 47 patients (11.4%, 95% CI 8.3-14.5) were found to have a
      contributing familial background. The implication is thus that every ninth
      patient with colorectal cancer represents a highly or intermediately increased
      risk of the disease among relatives. We conclude that the low frequency of
      individuals identified by family history alone makes the establishment of
      surveillance programs feasible.

PMID- 14574158
TI  - Genotype and phenotype of patients with both familial adenomatous polyposis and
      thyroid carcinoma.
AB  - The incidence of thyroid carcinoma in familial adenomatous polyposis (FAP) is
      thought to be 1%-2%, with the majority of cases being female. We have
      investigated the phenotype and genotype of 16 patients with FAP associated
      thyroid carcinoma. Among 1194 FAP patients studied in two high risk registries in
      North America (Familial Gastrointestinal Cancer Registry, Toronto and University
      California, San Francisco), 16 (1.3%) unrelated patients with FAP associated
      thyroid cancers were identified. Adenomatous polyposis coli (APC) gene testing
      was performed in 14 of the 16 cases. The average age of diagnosis for FAP and
      thyroid carcinoma was 29 years (range 17-52 years) and 33 years (range 17-55
      years), respectively. All FAP patients except 1 had more than 100 colonic
      adenomas. Extracolonic manifestations, beside thyroid cancer, were presented in
      81% (n = 13) of the patients, including gastric and duodenal polyps, desmoid
      tumor, osteoma, epidermoid cyst, sebaceous cyst and lipoma. Colorectal cancer was
      diagnosed in 38% (n = 6) of the patients. The pathology of the FAP associated
      thyroid cancer was predominantly papillary carcinoma. Germline mutations were
      identified in 12 of 14 patients tested. Mutations proximal to the mutation
      cluster region (1286-1513) were detected in 9 cases. Thyroid cancer in our FAP
      population was rare, predominantly in females and showed papillary carcinoma
      histology. Additionally, thyroid cancer in our patients occurred in the setting
      of classic FAP phenotype. Germline mutations were located predominantly outside
      the APC mutation cluster region.

PMID- 14574159
TI  - Spouse controls in family case-control studies: a methodological consideration.
AB  - In case-control studies on familial aggregation of disease, spouses may be chosen
      as convenient controls. In this article the pros and cons of this control group
      are discussed. It is argued that the use of spouse controls can be time- and cost
      efficient, because of easy accessibility and their ability to provide proxy data
      on the patients' relatives if necessary. Furthermore, with spouse controls a
      higher response rate and less recall bias can be expected compared to population
      controls. A theoretical drawback is the possibility of assortative mating related
      to genetic susceptibility of the disease under study. Using a simulation study it
      is illustrated that even strong assortative mating on a factor, which is strongly
      correlated with a true risk factor under study, will have a negligible effect on
      the observed extent of familial aggregation.

PMID- 14574161
TI  - An audit of familial juvenile polyposis at the Tel Aviv Medical Center:
      demographic, genetic and clinical features.
AB  - Familial juvenile polyposis (JP) is an uncommon genetic disorder that, if
      untreated, can lead to gastrointestinal cancer. To evaluate familial JP
      prevalence, phenotypic manifestations, causative mutations, treatment and
      compliance for diagnosis and follow-up in our registry. Since 1993 our familial
      JP patients were registered, followed-up before and/or after surgery and their
      families encouraged to have mutation analysis, endoscopic screening and
      treatment. Ten pedigrees were identified, all Jewish, but only one was Ashkenazi,
      six were Sepharadi and three were Oriental; the only mutation found was BMPR1A in
      two of six pedigrees examined. Of 139 first-degree relatives at risk for JP, 62
      (45%) had JP or cancer; 56 (40.3%) were available for follow-up and 35 entered
      the registry. Of these, 71% reported rectal bleeding, 40% had <20 colonic polyps,
      31% had 20-100 polyps; 2 had >100 gastric polyps. Cancer occurred in 22.9% (6
      colonic, 2 gastric) before familial JP diagnosis or during follow-up elsewhere or
      non-compliance for follow-up; however, 1 gastric cancer developed during our
      treatment. In 46% the initial clinical-pathological diagnosis was incorrect.
      Compliance for evaluation and follow-up of pedigree members and individual
      familial JP patients was inadequate in 20% and 26%, respectively. Familial JP
      does not occur in the Israeli Ashkenazi Jewish population at the expected
      proportion; it is often misdiagnosed and is inadequately recognized in Israeli
      non-Jews. Mutations were identified in only a minority of pedigrees despite
      comprehensive screening. The inadequate compliance for screening and follow-up
      needs to be addressed by educating the public, health care workers and health
      insurances.

PMID- 14574160
TI  - Familial melanoma: a complex disorder leading to controversy on DNA testing.
AB  - The initial enthusiasm generated by the discovery of the first susceptibility
      gene found for melanoma has slightly dampened over recent years. For the majority
      of melanoma families the underlying gene defect is still not known, so the search
      for other melanoma genes is continuing. Also, the increased risk of melanoma does
      not seem to be restricted to mutation carriers, but is present even in non
      mutation carriers in melanoma families. The underlying defect of familial
      melanoma is less straightforward than previously thought; both environmental and
      hereditary risk modifiers intermingle in a perplexing way. This makes familial
      melanoma a complex disorder which deserves the close attention of both clinicians
      and researchers, especially as the opinion on gene testing in familial melanoma
      has not yet achieved consensus. On the one hand, there is a rising demand from
      families for genetic testing; on the other hand, there is the clinicians' concern
      about the value of such testing.

PMID- 14574162
TI  - The inframe MSH2 codon 596 deletion is linked with HNPCC and associated with lack
      of MSH2 protein in tumours.
AB  - Hereditary nonpolyposis colorectal cancer (HNPCC) may be caused by germline
      truncating mutations in DNA mismatch repair (MMR) genes. Whether or not missense
      or inframe mutations are disease-associated has become a practical clinical
      problem, because predictive genetic testing is employed to select high-risk
      persons for clinical examinations. Clinical examinations may reveal polyps to be
      removed and prevent cancer. One large kindred applying for health care had a
      N596del mutation in the MSH2 gene. The aim of this study was to determine whether
      or not the inframe mutation in this family was associated with disease, and to
      examine the tumours for presence of the MSH2 protein by immunohistochemistry. We
      demonstrated that the mutation was linked to disease with lod score 5.7 in the
      family, and all examined, but one manifest cancer, lacked the MSH2 protein.

PMID- 14574164
TI  - Quality of life in patients with multiple endocrine neoplasia type 1 (MEN 1).
AB  - To study quality of life among patients living with a hereditary tumor syndrome,
      the small group with multiple endocrine neoplasia type 1 (MEN1) was selected. It
      is characterized by multifocal adenomas of the pancreas, parathyroid, anterior
      pituitary and other endocrine glands. Patients were assessed at an in-hospital
      stay and six months later at home. Patients at a specialist ward for MEN1 were
      recruited consecutively (n = 36) during one year. Eighty-one percent participated
      (n = 29). Four questionnaires were used: the Hospital Anxiety and Depression
      Scale (HADS), the Impact of Event Scale (IES), the Life Orientation Test (LOT)
      and the Short Form-36 (SF-36). Psychosocial outcome measures (anxiety,
      depression, intrusion, avoidance) changed only marginally between the in hospital
      stay and six months later at home. However, depression increased for patients
      categorized as having a high burden of disease and treatment. Compared to
      population-based norm values, the SF-36 scores of the patient group MEN1were
      lower for General Health and Social Functioning. Optimism assessed at the
      hospital was a predictor of Mental Health six months later. Most MEN 1 patients
      (70%) were pessimists. Patients having a higher burden of disease and treatment
      are in need of support after discharge. Patients could easily be monitored with
      questionnaires and, when indicated, offered help for their psychosocial distress.

PMID- 14574163
TI  - Does the occurrence of certain rare cancers indicate an inherited cancer
      susceptibility?
AB  - We sought to determine whether rare cancers indicate an increased risk of
      inherited cancer susceptibility. We ascertained 77 individuals with rare cancers
      which occur with increased relative risk in carriers of germline BRCA1/BRCA2
      (fallopian, young-onset pancreatic) or HNPCC (biliary, small intestinal,
      urothelial, gallbladder, young-onset pancreatic) mutations. Individuals with two
      primary neoplasms (7), or with a first- or two second-degree relatives with
      breast/ovarian cancer were tested for BRCA1/BRCA2 mutations (18); those with two
      primary HNPCC cancers or one first degree relative with an HNPCC-related cancer
      were tested for mutations in MLH1/MSH2 (19). Of these 77 individuals with cancer
      (19 fallopian, 8 gallbladder, 17 biliary, 17 pancreatic, 11 urothelial, 5 small
      intestinal), 39 (50.6%) had at least one first degree relative with cancer
      (excluding lung and skin); two conformed to Bethesda HNPCC criteria. No
      definitely pathogenic germline MLH1 and MSH2 mutations were found in 19
      individuals, although 2 MSH2 variants were detected. A family history of
      breast/ovarian, HNPCC or colon cancer in a first degree relative was found in 40%
      of fallopian, 20% of biliary, 35% of pancreatic, 27% of urothelial and 20% of
      small bowel cancer patients. A BRCA1 frameshift mutation was detected in a woman
      with fallopian (54 y) and breast (39 y) cancers, and a BRCA2 nonsense mutation in
      a woman with biliary (48 y) and breast (45 y) cancers. This study supports the
      premise that the occurrence of rare (especially double primary) cancers does
      indicate an increased cancer susceptibility, although the numbers of cases
      ascertained were too small to draw firm conclusions.

PMID- 14574165
TI  - The effect of disease penetrance, family size, and age of onset on family history
      with application to setting eligibility criteria for genetic testing.
AB  - The concept of family history of disease has been used as a surrogate for genetic
      susceptibility in many epidemiological studies and has also been important as a
      criterion for selecting individuals for genetic testing. However, little is known
      about the precise interplay between the true genetic model (genotype-specific
      penetrances, age of onset distribution), life expectancy, and reproductive
      patterns in determining the level of family history. In order to address these
      questions, we performed a simulation study to address these relationships.
      Factors examined were the age-, sex-, and genotype-specific penetrance of the
      disease and the distribution of the number of offspring per family. When
      considering the average number of affected individuals among first-degree
      relatives of mutation positive probands, penetrance-related factors accounted for
      64% of the variance in the average number of affected first-degree relatives, and
      58% of the variance in the number of affected first- or second-degree relatives.
      In general, the average proportion of mutation-positive probands with at least
      one affected first-degree relative was low, especially for a sex-limited disease,
      ranging between 20% and 46%, depending on the lifetime penetrance in mutation
      carriers. Lack of family history among first-degree relatives of mutation
      positive probands is not necessarily unexpected even for loci conferring
      relatively high lifetime risk. In selecting probands for genetic testing, we
      found that under a wide variety of conditions, criteria based on the number of
      affected among first- and second-degree relatives were superior to those based on
      first-degree family history alone.

PMID- 14574166
TI  - Attenuated familial adenomatous polyposis (AFAP). A review of the literature.
AB  - Over the last decade, a subset of familial adenomatous polyposis (FAP) patients
      with a milder course of disease termed attenuated familial adenomatous polyposis
      (AFAP) has been described. AFAP is not well-defined as a disease entity - the
      reports on AFAP are largely casuistic or only deal with a few kindreds--and the
      diagnostic criteria and methods of investigation differ markedly. The true
      incidence and frequency of AFAP is not known. The mutations in APC associated
      with AFAP have mainly been detected in three parts of the gene: in the 5' end
      (the first five exons), in exon 9 and in the distal 3' end. The main features of
      AFAP are 100 or less colorectal adenomas with a tendency to rectal sparing, a
      delay in onset of adenomatosis and bowel symptoms of 20-25 years, a delay in
      onset of colorectal cancer (CRC) of 10-20 years and death from CRC of 15-20
      years, and although the lifetime penetrance of CRC appears to be high, CRC does
      not seem to develop in nearly all affected patients. A more limited expression of
      the extracolonic features is seen, but gastric and duodenal adenomas are
      frequently encountered. Colonoscopy is preferred to sigmoidoscopy, should begin
      at the age of 20-25 years and no upper age limit of stopping surveillance is
      justified. Regular esophago-gastro- duodenoscopy (EGD) is recommended. Until
      further research has provided us with a more substantiated knowledge about AFAP
      changes in current surveillance and treatment are not recommended. Prophylactic
      colectomy with ileorectal anastomosis (IRA) is recommended in most patients.

PMID- 14574168
TI  - High detection rate for BRCA2 mutations in male breast cancer families from North
      West England.
AB  - 33 families with a history of male breast cancer aged 60 or less or with a family
      history of male and female breast cancer were screened for the presence of BRCA2
      mutations. 12 pathogenic BRCA2 mutations were identified (36%) in samples from an
      affected family member. All mutations segregated with disease where it was
      possible to check. Of the 14 families fulfilling BCLC criteria, 9 (64%) had
      mutations whilst only 3/16 (19%) of male breast cancer patients with less
      significant female breast cancer family history having a mutation. All 3 families
      with ovarian cancer and 3 families with multiple male breast cancer cases had
      BRCA2 mutations. These data are a further guide to how to prioritise samples for
      BRCA2 mutation analysis.

PMID- 14574167
TI  - Genetic susceptibility to prostate cancer: a review.
AB  - A genetic component in prostate cancer has been recognized since decades. Through
      numerous epidemiological and molecular biological studies, much evidence has
      accumulated in favor of a significant but heterogeneous hereditary component in
      prostate cancer (PCa) susceptibility. Since the mapping of a high-penetrant PCa
      susceptibility locus at 1q24-25, much attention has been paid to the
      identification of PCa susceptibility genes. So far, seven loci have been mapped,
      and at three of these loci, genes have been cloned and mutations identified. Yet
      their role in hereditary and sporadic disease is still under debate and probably
      very modest. Although research on hereditary prostate cancer has improved our
      knowledge of the genetic etiology of the disease, still a lot of questions remain
      unanswered. Here, we aim to review the genetic epidemiological and molecular
      biological research in the field of hereditary prostate cancer and the problems
      that are encountered with this research.

PMID- 14574169
TI  - Knowledge about breast cancer risk factors and hereditary breast cancer among
      early-onset breast cancer survivors.
AB  - Little is known about knowledge levels regarding hereditary breast cancer among
      breast cancer survivors. This study explored, among women with early-onset breast
      cancer (<50 years): 1) knowledge regarding breast cancer risk factors and
      hereditary breast cancer; and 2) differences in knowledge based on risk for
      hereditary disease. Participants recruited from 34 Virginia hospitals responded
      to two questionnaires. The Family History Questionnaire assessed risk for
      hereditary breast cancer. The Knowledge, Attitudes, and Beliefs Questionnaire
      evaluated knowledge of general breast cancer risk factors and hereditary breast
      cancer. Of 314 respondents, 273 (87%) returned both questionnaires. A total of
      137 (52%) participants met the study's criteria for hereditary breast cancer
      risk. Most participants knew common breast cancer-associated risk factors,
      including family history of breast cancer. Only 35% recognized family history of
      non-breast malignancies as a risk factor for breast cancer. Most participants
      recognized that prophylactic mastectomy does not eliminate breast cancer risk
      (63%), that not all women carrying a mutation develop disease (73%), and that men
      can develop breast cancer (96%). The majority selected 'I don't know' for
      knowledge of several characteristics of hereditary breast cancer, including:
      early-onset disease (54%); multifocal or bilateral disease (62%); risk
      transmission through fathers (58%); association with other cancer types (61%);
      and male breast cancer (70%). Knowledge regarding hereditary breast cancer did
      not vary between women with suspected hereditary disease and those with presumed
      sporadic disease. These data highlight the need for information regarding
      hereditary breast cancer for early-onset breast cancer survivors.

PMID- 14574170
TI  - Prophylactic oophorectomy in Ontario.
AB  - OBJECTIVE: To determine the indications, patterns of practice, and complication
      rates for prophylactic oophorectomy in Ontario. METHODS: From hospital discharge
      abstracts, 82 hospitals were identified where at least one patient had a
      prophylactic oophorectomy since 1992. Ethics approval for the chart review was
      obtained from 41 hospitals (50%), was denied at 10 (12%) and is pending at 31
      facilities. Using the International Classification of Disease diagnostic code for
      family history of ovarian cancer (V16.4) and prophylactic oophorectomy (V50.42),
      the medical records departments were asked to retrieve the charts. One abstractor
      reviewed the charts using a standard form to collect demographic information,
      indications for surgery, details of surgery and complications. RESULTS: From 1992
      1998, 263 women underwent PO in 41 hospitals. A BRCA1 or BRCA2 mutation was
      recorded in 16 cases. Thirty-six patients had a past history of breast cancer. In
      127 women, a family history was the sole reason for surgery; the remaining 136
      women had a coexisting gynecologic complaint. Laparotomy was used exclusively in
      155 cases, laparoscopy in 79 and vaginal access in 12 cases. Seventeen women
      required conversion to laparotomy during the operation. The mean length of
      hospital stay was 3.7 days (0-14 days). Thirty-six women (14%) had complications.
      CONCLUSION: We have described the indications for surgery, trends in surgical
      practice and surgical complications for women receiving prophylactic oophorectomy
      in Ontario. Prior to prophylactic oophorectomy, the indications and benefits
      should be clear to both patient and physician. Optimally, all women should
      receive genetic counseling to help define risk for ovarian and breast cancer,
      medical and surgical options, impact of oophorectomy on cancer risk, risk of
      surgical complications, and the consequences and management of surgical
      menopause.

PMID- 14574171
TI  - Quality of life and psychosexual adjustment after prophylactic oophorectomy for a
      family history of ovarian cancer.
AB  - OBJECTIVES: 1) To evaluate a woman's satisfaction with the decision to have a
      prophylactic oophorectomy for family history of ovarian cancer. 2) To explore the
      potential costs related to surgery such a menopausal symptoms and satisfaction
      with sexual functioning. METHODS: Women who had undergone a prophylactic
      oophorectomy for a family history of ovarian cancer in Ontario were invited to
      participate. Forty women returned a package of questionnaires addressing
      demographic information, family history, decisional conflict, risk comprehension,
      menopause-specific quality of life, satisfaction with sexual function, and other
      psychosocial questionnaires. RESULTS: The mean age of respondents was 54.8 years.
      Perceived risk for developing ovarian cancer decreased significantly after
      surgery (p = 0.0001). Overall quality of life on the SF-36 Health Survey
      demonstrated a level consistent with emotional and physical wellbeing in the
      general population. The Menopause-Specific Quality of Life scores were reduced
      compared to women of similar age on all parameters: vasomotor symptoms,
      psychosocial support, physical status and sexual quality of life. Satisfaction
      with sexual functioning was moderately to extremely compromised in 42.1%-53.7% of
      women. CONCLUSION: While this study shows that women who choose to have
      prophylactic oophorectomy for a family history of ovarian cancer have a good
      overall quality of life and significant decrease in risk perception as a result
      of surgery, they experience menopausal symptoms and compromised sexual
      functioning.

PMID- 14574172
TI  - Comparison of physicians' and cancer prone women's attitudes about breast/ovarian
      prophylactic surgery. Results from two national surveys.
AB  - Prophylactic surgery is a major issue for breast/ovarian cancer prone women. Bio
      clinical data to help in the decision-making are not sufficient. In this context
      of uncertainty, physicians' and women's attitudes to prophylactic surgery is
      information of great value. The physicians' attitudes were assessed by a
      randomised national sample of practitioners involved in breast and ovarian cancer
      management. The patients' attitudes were appraised with a pre-consultation self-
      administered questionnaire presented during a one-year period to all women in
      five cancer genetic clinics chosen, for their representative geographical
      locations and their activity level. Consent to prophylactic surgery is higher
      among physicians than among patients (p < 0.0001). Acceptability of mastectomy is
      lower than that of oophorectomy in both patients and physicians (p < 0.0001 in
      both groups). In addition, age at which the intervention is proposed to be
      performed is a key determinant for both mastectomy and oophorectomy
      acceptability, in both physicians and patients (p < 0.001 for each comparison).
      Particularly, the age of 40 years seems to be a critical threshold for the
      acceptability of prophylactic oophorectomy. In contrast, respondents' age at the
      time of the survey has no significant effect on the acceptability rate. The
      higher acceptability rate of prophylactic oophorectomy compared to that of
      mastectomy observed in the physicians' survey is paradoxical because a more
      substantial medical impact on life expectancy was expected from the latter. Our
      results indicate that assumed reduced mortality is not the main criterion
      steering acceptability. It was anticipated that prophylactic mastectomy should be
      rarely performed in France.

PMID- 14574173
TI  - MRI screening for breast cancer in women with familial or genetic predisposition:
      design of the Dutch National Study (MRISC).
AB  - Mammography screening of women aged 50-70 years for breast cancer has proven to
      be effective in reducing breast cancer mortality. There is no consensus about the
      value of breast cancer screening in women aged 40-49 years. Five to ten per cent
      of all breast cancers are hereditary. One of the options to reduce the risk of
      breast cancer mortality for women with a familial or genetic predisposition is
      intensive surveillance. However, the effectiveness of mammography screening for
      breast cancer in these women, who are mainly younger than 50 years, is unproven.
      MRI might increase the effectiveness of screening in women with a familial or
      genetic predisposition. This paper describes the design of the Dutch national
      study for Magnetic Resonance Imaging (MRI) screening in women with a familial or
      genetic predisposition. The aims of this study are to investigate: the value of
      regular surveillance in women with a familial or genetic predisposition for
      breast cancer, the efficacy of MRI as compared to mammography, cost-effectiveness
      of regular screening and quality of life during surveillance. Included are women
      with a lifetime risk of familial breast cancer of 15% or more or BRCA1/2 mutation
      carriers, who visit one of the Dutch family cancer clinics. The aim is to include
      2,500 women. The study started on 1 November 1999. On 1 January 2002, more than
      1,700 women, including 210 proven carriers of a BRCA1 or BRCA2 mutation, were
      included in the study.

PMID- 14574174
TI  - Prediction of the outcome of genetic testing in HNPCC kindreds using the revised
      Amsterdam criteria and immunohistochemistry.
AB  - BACKGROUND AND AIMS: Hereditary non-polyposis colorectal cancer (HNPCC) may be
      caused by mutations in the mismatch repair (MMR) genes MLH1, MSH2 or MSH6. Family
      history (Amsterdam criteria) has traditionally been used to select patients for
      mutation testing. It has been demonstrated that germline mutations in the MMR
      genes are associated with lack of the corresponding gene product as assessed with
      immunohistochemistry (IHC) in tumour specimens. The aim of the study was to
      assess the value of the Amsterdam criteria II and IHC in predicting germline
      mutations. METHODS: Fifty-six families that were previously tested for MLH1, MSH2
      and MSH6 mutations were selected for this study. All pedigrees were extended and
      verified and the families were scored according to the original (I) and the
      revised Amsterdam criteria (II). The probabilities for MLH1 and MSH2 mutations
      were calculated by logistic regression. In addition, all available tumour
      material from indexed family members was examined by IHC for the presence of the
      three gene products. RESULTS: Three out of seven (39%) families where the
      mutation could be identified complied with the Amsterdam criteria I, while all
      seven (100%) met the Amsterdam criteria II. All families carrying a MLH1 or MSH2
      mutation had > 15% calculated probability of finding a mutation. Tumours from all
      seven mutation carriers lacked the immunohistochemical expression of the
      corresponding MMR gene. CONCLUSION: The results indicate that the Amsterdam
      criteria II in combination with immunohistochemistry of the mismatch repair
      proteins in tumours may be a cost-effective approach to select families for
      mutation analysis.

PMID- 14574175
TI  - Cancer prone persons. A randomized screening trial based on colonoscopy:
      background, design and recruitment.
AB  - OBJECTIVE: Evidence-based counseling and prevention are not available so far for
      hereditary cancer prone persons, since we lack data based on clinical trials.
      There are very few high-risk persons in the population as a whole. Based on a
      familial history analysis, only 1.2% of all healthy volunteers attending
      screening centers reached the arbitrary high-risk level defined as a Relative
      Risk of more than 4. We describe a randomized trial based on colonoscopic
      screening for colorectal cancer on a sub-group of high-risk group persons.
      MATERIALS AND METHODS: Among the 77 members of the French Institutional
      Preventive Center Network, 37 took part in this protocol. During the first 3
      years, 850,000 persons were interviewed at these 37 Health centers. The
      enrollment process was particularly time-consuming, since a large amount of
      information had to be delivered to the participants. RESULTS: The mean rate of
      recruitment of eligible candidates was far lower than predicted, averaging only
      1.4 per 1,000 persons interviewed instead of the 9/1,000 expected. This mean
      figure was based, however, on inclusion rates ranging from 0.06/1,000 to 7/1,000
      among the different centers. The low rates of recruitment were mainly due to the
      inter-center heterogeneity (differences in commitment and in the resources), and
      to the fact that the acceptability of undergoing a colonoscopy turned out to be
      lower than predicted. CONCLUSION: Population trials on cancer prone persons are
      feasible, but vast numbers have to be pre- screened to identify the few people
      with a high hereditary risk and willing to accept screening within a controlled
      trial.

PMID- 14574176
TI  - Jan Peutz, Harold Jeghers and a remarkable combination of polyposis and
      pigmentation of the skin and mucous membranes.

PMID- 14574177
TI  - Comment on Elit et al.: prophylactic oophorectomy in Ontario.

PMID- 14574178
TI  - Apparent Mendelian inheritance of breast and colorectal cancer: chance, genetic
      heterogeneity or a new gene?
AB  - It is not uncommon for cancer geneticists to be referred families with apparently
      Mendelian co-inheritance of breast and bowel cancer. Such families present a
      particular problem as regards the intensity of their screening for these diseases
      and the utility of genetic testing. Many 'breast-colon' cancer families probably
      result from chance clustering of two common cancers. Other 'breast-colon' cancer
      families may result from known cancer syndromes, such as hereditary breast
      ovarian cancer or hereditary non-polyposis colon cancer, either by conferring a
      high risk of one cancer type and a slightly increased risk of the other, or
      through a predisposition to one of the two cancers and chance occurrence of the
      other. Anecdotally, however, many geneticists wonder about the existence of a
      distinct 'breast-colon cancer syndrome', since some families present good a
      priori evidence of genetic disease and yet cannot readily be accounted for by
      known genes or chance. The identification of unknown 'breast-colon cancer' genes
      is likely to be difficult, relying primarily on candidate gene analysis,
      including loci separately implicated in breast or colorectal cancer, or in other
      multiple cancer syndromes. Studies such as those on APC I1307K and CHEK2 1100delC
      may suggest the way forward for the identification of 'breast-colon cancer'
      genes.

PMID- 14574180
TI  - Advance care delivery through technology.

PMID- 14574179
TI  - Risk models used to counsel women for breast and ovarian cancer: a guide for
      clinicians.
AB  - Advances in the identification and treatment of breast and ovarian cancer have
      lead to a need for reliable estimates of susceptibility risk associated with
      these two cancers. These estimates may be used in clinical settings to identify
      individuals at increased risk of developing disease or of being a carrier of a
      disease susceptibility allele. Accurate assessment of these probabilities is
      important given the potential implications for medical decision-making including
      the identification of patients who might benefit from preventive measures,
      genetic counseling or from entry into clinical trials. A wide range of empirical
      and statistical models has been proposed, particularly for breast cancer risk
      prediction, including those that utilize logistic regression or Bayesian
      modeling. The specific data used to create the various risk models also varies
      and may include molecular, epidemiologic, or clinical information. This overview
      presents definitions of risk used in clinical oncology as well as several of the
      more frequently used methods of risk estimation for breast and ovarian cancer. In
      addition, the means by which different methods are able to provide a measure of
      error or uncertainty associated with a given risk estimate will be discussed.

PMID- 14574181
TI  - Barcoding makes its mark on daily practice.

PMID- 14574182
TI  - New uses for wireless technology.

PMID- 14574183
TI  - Explore all-encompassing electronic health records.

PMID- 14574184
TI  - The e-learning answer.

PMID- 14574185
TI  - Make computer-based training user-friendly.

PMID- 14574187
TI  - Valgus intertrochanteric osteotomy for malunion and nonunion of trochanteric
      fractures.
AB  - OBJECTIVE: To evaluate the results of valgus intertrochanteric osteotomy for
      varus nonunion and malunion of trochanteric fractures. SETTING: University
      hospital. DESIGN: Retrospective clinical study. PATIENTS: Fifteen patients (age
      range 29-84 years) with varus malunion (11 cases) or varus nonunion (4 cases).
      Indication for surgery was nonunion or varus malunion with limb shortening
      greater than 2 cm associated with limp, abductor muscle insufficiency, hip pain,
      and back pain. INTERVENTION: The patients were treated by a valgus
      intertrochanteric osteotomy fixed with a 120 degrees double-angled blade plate.
      RESULTS: Average follow-up was 5.5 years (range 2-10 years). Fourteen patients
      healed without complications: 12 patients within 4 months; 2 delayed unions
      within 6 months. One patient required revision surgery for a loss of fixation due
      to a fall 6 weeks after surgery. This osteotomy also healed. Average lengthening
      achieved by osteotomy was 2 cm (range 1-5 cm). In all patients, the resulting
      range of flexion in the hip joint was greater than 90 degrees, Harris hip score
      before surgery was 73 points (range 61-83), and after surgery 92 points (range 76
      98). Osteoarthritis or avascular necrosis of the femoral head did not develop in
      any of the cases. CONCLUSION: Valgus intertrochanteric osteotomy is an effective
      procedure that reliably restores hip function in trochanteric malunion or
      nonunion.

PMID- 14574188
TI  - The second hip fracture--an analysis of 84 elderly patients.
AB  - OBJECTIVES: Evaluation of patients with a second hip fracture, which means a
      fracture of the contralateral hip. DESIGN: Retrospective database analysis.
      SETTINGS: Academic teaching hospital. PATIENTS: All patients who were admitted
      for their second hip fractures between November 1999 and September 2001 and had
      their first hip fracture treated in our institution. INTERVENTION: In this study,
      we epidemiologically analyzed the fracture types, the interval between the two
      fractures, general status of the patients, type of operation performed, and the
      postfracture independence level. RESULTS: This survey comprises 84 patients (65
      females and 19 males). Their ages ranged from 57 to 91 years (mean: 79) and 58 to
      93 years (mean: 82) for the first and the second operation, respectively. The
      interval between the operations ranged from 2 to 297 months (mean: 35 months,
      median: 30 months). Twenty-three patients had subcapital fractures in both hips.
      In 54 patients, bilateral intertrochanteric fractures were noted. Only 7 patients
      had a previous subcapital fracture and a second intertrochanteric fracture. The
      general status of the patients' health was defined by the number of pre-existing
      major medical conditions and was found to be between 0 and 4 (mean: 2.15). Thirty
      two patients (38%) had additional fractures somewhere between 1 and 8 years prior
      to the hip fracture (vertebra, proximal humerus, or distal radius). Sixty-eight
      and 56 out of the 84 patients reached the same mobility status after the first
      and second operation, respectively. CONCLUSIONS: A tendency was found for the
      second hip fracture to be of the same type as the previous one. Most patients
      showed a good potential for rehabilitation and for maintaining their prefall
      functional level.

PMID- 14574189
TI  - Biomechanical evaluation of a new type of hip compression screw with retractable
      talons.
AB  - OBJECTIVES: We investigated the biomechanical performance of a compression hip
      screw with four reversibly deployable talons. We hypothesized that the talons
      would increase purchase strength of the lag screw and prevent rotation of the
      femoral head by resisting torsional forces between the lag screw and the femoral
      head. DESIGN: Reproducible, stable two-part intertrochanteric fractures were
      created on matched pairs of embalmed human femurs. Fractures were fixed using the
      compression hip screw with either the talons deployed (talon) or not deployed
      (screw) configuration. Pre- and postimplantation radiographs and dual energy x
      ray absorptiometry scans were used to ensure geometric and balanced equivalency
      between contralateral limbs. Torsional tests were performed on femoral pairs at 1
      Hz for 5000 cycles prior to torque failure. Compression tests were performed on
      femoral pairs with the screw in the inferior or central position. RESULTS: Peak
      torque and torque at 15 degrees of rotation were significantly greater for the
      talon versus screw device (6.5 +/- 1.7 Nm vs. 1.9 +/- 1.7 Nm for peak torque, P =
      0.0002; and 4.2 +/- 2.0 Nm vs. 1.2 +/- 1.2 Nm for torque at 15 degrees rotation,
      P = 0.003). The peak compressive forces generated by the talon device were
      significantly greater than for the screw device in the inferior position (P =
      0.005), with compression values of 1398 +/- 467 N and 713 +/- 323 N,
      respectively. Peak compression forces did not differ significantly between talon
      and screw devices in the central position. CONCLUSIONS: Talon deployment
      significantly improved interfragment compression and torsional strength.
      Engagement or penetration into or through the cortical bone at the base of the
      femoral head-neck junction in the inferior lag screw position is the critical
      technical step to maximize the talon purchase.

PMID- 14574190
TI  - The "Gull Sign": a harbinger of failure for internal fixation of geriatric
      acetabular fractures.
AB  - OBJECTIVES: To identify factors affecting the outcomes of surgery for acetabular
      fracture in patients over the age of 60 years. DESIGN: Retrospective review of
      records and radiographs; current examination, radiographs and outcome surveys
      when possible. SETTING: Academic, Level 1 trauma center. PATIENTS/PARTICIPANTS:
      Forty-eight patients over age 60 with displaced acetabulum fractures.
      INTERVENTION: Surgical reduction and fixation. MAIN OUTCOME MEASUREMENTS:
      Clinical ratings and radiographic evaluations, Short Musculoskeletal Functional
      Assessment survey (SMFA), SF-36, and hip-specific questions. Radiographs were
      evaluated using the criteria of Matta. RESULTS: Ten patients died since surgery.
      Four were lost to follow-up. Seven had >12 months of follow-up information in the
      chart. Twenty-seven had current evaluations for the study. Average follow-up was
      37 months, range 1-114 months. The average age at surgery was 71.6 years (range
      61-88). No perioperative deaths occurred. Initial reductions achieved: 61%
      anatomic, 34% imperfect, and 5% poor. A specific radiographic finding
      (superomedial dome impaction) predictive of failure was identified. This was
      designated the "Gull Sign." These patients had inadequate reduction, early
      fixation failure, or medial/superior joint narrowing and subluxation. Functional
      outcomes in patients with current examination were similar to age-matched
      controls. Radiographic outcomes: 30% excellent, 30% good, 9% fair, 23% poor, and
      7% arthroplasty. Anatomic reduction was closely related to good or excellent
      radiographic result. CONCLUSIONS: While some patients over sixty years of age can
      have satisfactory functional outcomes after acetabular fracture fixation, a
      significant number will have failure of the procedure. Osteopenic patients with
      superomedial dome impaction (the Gull Sign) did not benefit from attempted open
      reduction and internal fixation in this series.

PMID- 14574191
TI  - Induction of chondrocyte apoptosis following impact load.
AB  - OBJECTIVE: To investigate the presence and extent of chondrocyte apoptosis
      following impact load of articular cartilage in an in vivo model. DESIGN: An in
      vivo animal model, using a pendulum device and New Zealand White rabbits, was
      designed to study the effects of impact load on the development of chondrocyte
      apoptosis. Animals were placed into either a High Impact group or a Low Impact
      group, and the right medial femoral condyle was impacted with a single impact
      load. A sham operation was performed on the left limb, and this cartilage served
      as the control. SETTING: Academic medical center. PARTICIPANTS: New Zealand White
      rabbits (3 months). INTERVENTION: Impact load to the right medial femoral
      condyle. MAIN OUTCOME MEASURES: Three different methods were used to assess the
      presence and extent of chondrocyte apoptosis: 1) light microscopy (hematoxylin
      and eosin and terminal dUTP nick end labeling staining); 2) transmission electron
      microscopy; and 3) fluorescent microscopy with Hoechst 33342 staining. Secondary
      outcome measures included determination of the magnitude of impact force and time
      to peak force. RESULTS: Light microscopy demonstrated chondrocytes with changes
      consistent with apoptosis including condensed nuclei, deep eosinophilic
      cytoplasmic staining, and vacuolization within the impacted specimens. Terminal
      dUTP nick end labeling staining-stained specimens had a high degree of positively
      stained cells (60%) in both injured and uninjured specimens. Transmission
      electron microscopy of the impacted specimens demonstrated numerous chondrocytes
      with changes characteristic of apoptosis, including nuclear and cellular
      fragmentation, volume shrinkage, and cytoplasmic vacuolization. Eleven percent of
      the cells in the High Impact group had changes consistent with apoptosis, versus
      3% for the low impact group and <1% for the sham specimens. The High Impact group
      received a statistically significant greater stress than the Low Impact group.
      Impact group (P < 0.05), and the average time to peak force was 0.021 seconds for
      each impact group. CONCLUSIONS: The current data strongly indicate that in vivo
      chondrocyte apoptosis can be stimulated by the application of a single, rapid
      impact load and that the extent of chondrocyte apoptosis is related to the amount
      of load applied. The contribution chondrocyte apoptosis makes to the development
      of posttraumatic arthritis following joint injury or intra-articular fracture
      still remains to be determined.

PMID- 14574192
TI  - Removal of the broken tip of a hexagonal screwdriver from a nail end cap using a
      magnetic bar.
AB  - The tip of the hexagonal screwdriver can be broken and retained in the recess of
      the end cap of an intramedullary nail. It can happen when the position of the
      patient's limb suddenly changes during the tightening procedure. Removal of the
      broken tip is necessary due to metal incompatibility and for the potential of a
      future procedure. A simple solution for this problem is presented, the use of a
      magnetic bar normally used for removal of orbital metallic foreign bodies.

PMID- 14574193
TI  - Temporary transarticular stabilization of a glenohumeral fracture dislocation: a
      technique revisited.
AB  - SUMMARY: A 93-year-old patient with an unstable fracture-dislocation of the
      glenohumeral joint and medical problems that precluded open surgery was first
      managed by an unsuccessful closed reduction. Temporary transarticular pin
      fixation then was used successfully, allowing the patient to return to early
      activities with minimal morbidity.

PMID- 14574194
TI  - Transphyseal fracture-dislocation of the femoral neck: a case report and review
      of the literature.
AB  - We describe a case of transphyseal hip fracture-dislocation in a 7.5-year-old
      patient who was treated initially by open reduction and internal fixation. Soon
      after the injury, the femoral head developed avascular necrosis. The treatment
      was focused on maintaining adequate hip range of motion and providing femoral
      head containment with a combined subtrochanteric femoral osteotomy and shelf
      acetabuloplasty. The patient's young age and good hip remodeling potential
      contributed to the favorable clinical outcome 3 years after the injury. The long
      term prognosis remains guarded, however.

PMID- 14574195
TI  - Stress fracture of an os peroneum.
AB  - Fracture of the os peroneum is relatively rare, and a stress fracture of the os
      peroneum is even rarer. We report a case of stress fracture of the os peroneum in
      a 38-year-old laborer who had been working in a crouching position. X-rays showed
      a multipartite os peroneum. Bone scintigram showed uptake at the os peroneum. The
      histology of the excised os peroneum revealed various stages of fracture healing.
      Excision of the fractured os peroneum and reconstruction of the peroneus longus
      tendon by end-to-end suture resulted in an excellent outcome.

PMID- 14574196
TI  - Adult distal humeral metaphyseal fractures.

PMID- 14574197
TI  - What is race?

PMID- 14574198
TI  - Racial and ethnic differences in ocular anatomy.

PMID- 14574199
TI  - Ethnic differences in the systemic pharmacology for ophthalmologists.

PMID- 14574200
TI  - Racial differences in diabetes mellitus.

PMID- 14574201
TI  - Ethnic differences in diet and age-related maculopathies.

PMID- 14574202
TI  - Ethnic issues in neuroophthalmology.

PMID- 14574203
TI  - Eye disease in Latinos.

PMID- 14574204
TI  - Ethnic variation in the incidence and severity of retinopathy of prematurity:
      possible explanations, including racial differences in illness severity.

PMID- 14574205
TI  - Diabetic retinopathy in African Americans: vision impairment, prevalence,
      incidence, and risk factors.

PMID- 14574206
TI  - African American health disparities: glaucoma as a case study.

PMID- 14574207
TI  - Asian Americans: glaucoma.

PMID- 14574208
TI  - Asian Americans: cultural and anatomical considerations for periocular surgery.

PMID- 14574209
TI  - Asian Americans: myopia and refractive surgery.

PMID- 14574211
TI  - History of postoperative nausea and vomiting.

PMID- 14574212
TI  - Risk assessment of postoperative nausea and vomiting.

PMID- 14574213
TI  - Does meta-analysis increase our knowledge in the management of postoperative
      nausea and vomiting?

PMID- 14574214
TI  - Pharmacology of antiemetics.

PMID- 14574215
TI  - The use of propofol as an antiemetic.

PMID- 14574216
TI  - Role of complementary and novel antiemetic therapies.

PMID- 14574217
TI  - Management of postoperative vomiting in pediatric patients.

PMID- 14574218
TI  - Combination antiemetics: what is the evidence?

PMID- 14574219
TI  - Cost-effective Antiemesis.

PMID- 14574220
TI  - Postoperative nausea and vomiting and outcome.

PMID- 14574222
TI  - Comorbidity of alcohol dependence with attention-deficit hyperactivity disorder:
      differences in phenotype with increased severity of the substance disorder, but
      not in genotype (serotonin transporter and 5-hydroxytryptamine-2c receptor).
AB  - BACKGROUND: Nearly 50% of subjects with continuing symptoms of attention-deficit
      hyperactivity disorder (ADHD) in adulthood have been reported to show a comorbid
      substance use disorder. Both ADHD and alcohol dependence have a high genetic load
      and might even share overlapping sources of genetic liability. Recently, the
      functional relevant polymorphism within the promoter region of the serotonin
      transporter gene (5-HTT) and the 5-hydroxytryptamine-2c (5-HT2c) receptor
      Cys23Ser have been proposed as candidate genes for both entities. METHODS: We
      investigated phenotype and 5-HTT/5-HT2c genotype characteristics in 314
      alcoholics of German descent. RESULTS: There was no significant difference in 5
      HTT genotype or 5-HT2c allele distribution between alcoholics and matched
      controls. Sixty-seven alcoholics fulfilled DSM-IV criteria of ADHD with ongoing
      symptoms in adulthood and had a Wender Utah Rating Scale score greater than 90.
      Thirty had ADHD plus antisocial personality disorder. The subgroup of alcoholics
      with ADHD (ADHD+) showed a significantly higher daily and record ethanol intake
      per month, an earlier age at onset of alcohol dependence, and a higher frequency
      of suicidal ideation, court proceedings, and antisocial personality disorder. In
      our sample, more than 50% of type 2 alcoholics according to Cloninger consist of
      the ADHD+ and/or antisocial personality disorder-positive subjects. There were no
      differences in 5-HTT genotype or 5-HT2c allele distribution between the ADHD+
      subgroups and alcoholics without comorbidity and matched controls, respectively.
      CONCLUSIONS: Comorbidity of alcoholism and ADHD forms a distinct phenotype that
      shows an increased severity of the substance disorder. This phenotype contributes
      substantially to the so-called type 2 alcoholics according to Cloninger. In our
      sample, the functional relevant 5-HTT promoter and the 5-HT2c receptor Cys23Ser
      polymorphism do not contribute to the supposed common genetic predisposition of
      ADHD and alcohol dependence.

PMID- 14574223
TI  - Reverse selection for differential response to the locomotor stimulant effects of
      ethanol provides evidence for pleiotropic genetic influence on locomotor response
      to other drugs of abuse.
AB  - BACKGROUND: Addictive drugs share the ability to induce euphoria, which may be
      associated with their potential for abuse. Replicate mouse lines with high (FAST
      1, FAST-2) and low (SLOW-1, SLOW-2) sensitivity to ethanol-induced psychomotor
      stimulation (a possible animal model for the euphoria experienced by humans) have
      provided evidence for common genetic influences (pleiotropy) on sensitivity to
      the effects of ethanol and of GABA-A receptor acting compounds on locomotor
      activity. Differences between FAST and SLOW mice in locomotor response to certain
      other drugs were found later in selection. Reverse selection produced lines (r
      FAST-1, r-FAST-2, r-SLOW-1, r-SLOW-2) with similar locomotor responses to
      ethanol. These lines are well suited for asking whether the same alleles that
      influence sensitivity to ethanol are also responsible for these later arising
      differences in drug sensitivity. METHODS: Two replicate sets of forward- and
      reverse-selected FAST and SLOW lines were tested for the effects of multiple
      doses of morphine, cocaine, methamphetamine, nicotine, and scopolamine on their
      locomotor behavior. We predicted that differences in drug sensitivity between the
      FAST and SLOW lines would be reduced or eliminated in the reverse-selected lines.
      RESULTS: Differences in sensitivity to morphine, cocaine, methamphetamine, and
      nicotine that arose in earlier generations of the FAST-1 and SLOW-1 lines
      ultimately also appeared in the FAST-2 and SLOW-2 lines. However, some
      differences between the FAST-2 and SLOW-2 lines (those in response to cocaine and
      methamphetamine) were not seen until several generations after selection had been
      relaxed. In lines reverse-selected for sensitivity to ethanol, differences in
      sensitivity to the other drugs were decreased, eliminated, or even reversed. No
      differences in scopolamine response were found in the replicate 1 forward- or
      reverse-selected lines. However, a small difference in scopolamine response in
      the replicate 2 lines was reversed. CONCLUSIONS: Genes that influence the
      locomotor response to ethanol also influence locomotor response to other drugs
      with stimulant effects in the FAST and SLOW mice. The current data most strongly
      support this conclusion for sensitivity to morphine and nicotine.

PMID- 14574225
TI  - Hypericum perforatum CO2 extract and opioid receptor antagonists act
      synergistically to reduce ethanol intake in alcohol-preferring rats.
AB  - BACKGROUND: Hypericum perforatum extracts attenuate ethanol intake in alcohol
      preferring rats. The opioid receptor antagonists, naloxone and naltrexone, reduce
      ethanol intake in rats and humans. The combination of different agents that
      reduce ethanol intake has been proposed as an approach to the pharmacotherapy of
      alcoholism. This study evaluated the effect on ethanol intake of the combined
      administration of a CO2 H. perforatum extract and naloxone or naltrexone in
      genetically selected Marchigian Sardinian alcohol-preferring rats. METHODS: Ten
      percent (v/v) ethanol intake was offered 2 hr per day at the beginning of the
      dark phase of the reverse light-dark cycle. H. perforatum CO2 extract was given
      intragastrically, 1 hr before access to ethanol. Naloxone or naltrexone was given
      by intraperitoneal injection 10 min before the extract. RESULTS: H. perforatum
      CO2 extract reduced ethanol intake at 31 or 125 mg/kg, but not 7 mg/kg. These
      doses neither modified food or water intake during access to ethanol, nor reduce
      0.2% saccharin intake. Naloxone reduced ethanol and food intake at 3 or 5 mg/kg,
      but not 1 mg/kg. When naloxone 1 mg/kg was combined with the three doses of H.
      perforatum CO2 extract, the attenuation of ethanol intake was more pronounced
      than that observed after the administration of the extract alone. Alcohol intake
      was also significantly reduced by 7 mg/kg of H. perforatum CO2 extract combined
      with naloxone 1 mg/kg. The combined treatments never modified the rat's locomotor
      activity nor the simultaneous intake of food, water or 0.2% saccharin. Naltrexone
      reduced ethanol intake at 1 and 3 mg/kg, but not at 0.5 mg/kg. When naltrexone
      0.5 mg/kg was combined with H. perforatum CO2 extract 7 mg/kg, ethanol intake was
      markedly reduced. CONCLUSIONS: These findings provide evidence that H. perforatum
      CO2 extract and opiate receptor antagonists act synergistically to induce a
      pronounced and selective reduction of voluntary ethanol consumption in alcohol
      preferring rats.

PMID- 14574224
TI  - Effects of ethanol on the rat glutamate excitatory amino acid transporter type 3
      expressed in Xenopus oocytes: role of protein kinase C and phosphatidylinositol 3
      kinase.
AB  - BACKGROUND: Glutamate is a major excitatory neurotransmitter in the central
      nervous system. Glutamate transporters play a critical role in maintaining
      extracellular glutamate concentrations. We investigated the effects of ethanol on
      a neuronal glutamate transporter, excitatory amino acid transporter type 3
      (EAAT3), and the role of protein kinase C (PKC) and phosphatidylinositol 3-kinase
      (PI3 K) in mediating these effects. METHODS: EAAT3 was expressed in Xenopus
      oocytes by injection of EAAT3 messenger RNA. By using a two-electrode voltage
      clamp, membrane currents were recorded after the application of l-glutamate.
      Responses were quantified by integration of the current trace and reported as
      microcoulombs. Data are mean +/- SEM. RESULTS: Ethanol enhanced EAAT3 activity in
      a concentration-dependent manner. At 25, 50, 100, and 200 mM of ethanol, the
      responses were significantly increased compared with control values. Kinetic
      study demonstrated that ethanol (50 mM) significantly increased Vmax (3.48 +/-
      0.2 microC for control versus 4.16 +/- 0.24 microC for ethanol; n = 19; p < 0.05)
      without a significant change in the Km (65.6 +/- 11.1 microM for control versus
      55.8 +/- 9.6 microM for ethanol; n = 19; p > 0.05) of EAAT3 for glutamate.
      Preincubation of the oocytes with phorbol-12-myristate-13-acetate (PMA)
      significantly increased EAAT3 activity (0.98 +/- 0.08 muC for control versus 1.28
      +/- 0.09 microC for ethanol; n = 19; p < 0.05). However, there was no statistical
      difference among the responses of EAAT3 to PMA, ethanol, or PMA plus ethanol.
      Although the PKC inhibitors chelerythrine and staurosporine did not decrease the
      basal EAAT3 activity, they abolished the enhancement of EAAT3 activity by
      ethanol. Pretreatment with wortmannin, a PI3 K inhibitor, also abolished the
      ethanol-enhanced EAAT3 activity. CONCLUSIONS: These results suggest that acute
      ethanol exposure increases EAAT3 activity at clinically relevant concentrations
      and that PKC and PI3 K may be involved in mediating these ethanol effects.

PMID- 14574226
TI  - Impairment in cognitive functions after multiple detoxifications in alcoholic
      inpatients.
AB  - BACKGROUND: Repeated experience of withdrawal from alcohol results in a kindling
      like process leading to increased likelihood and severity of convulsions during
      detoxification. The aim of this study was to determine whether repeated
      withdrawals affect cognitive function. METHODS: We investigated alcoholic
      patients undergoing detoxification in an inpatient setting, using tasks sensitive
      to dysfunction of prefrontal areas. The tasks applied were two maze tasks from
      the Wechsler Intelligence Scale for Children, the color Stroop task, and the
      vigilance task for adults and the delay task from the Gordon Diagnostic System.
      Forty-two abstinent alcoholic patients who were no longer receiving
      pharmacotherapy for detoxification participated. RESULTS: Compared to a group of
      forty-three social drinkers matched for age, sex, and verbal IQ, the alcoholic
      patients took more time to complete maze 1 and made more errors in both mazes.
      Alcoholics made more commission errors and gave fewer correct answers in the
      vigilance task. No differences were found in the color Stroop task between
      alcoholic patients and social drinkers. Patients with 2 or more detoxifications
      were more impaired in the maze 1, in the vigilance task and in the delay task
      than patients with a single, or no previous detoxification. When patients were
      reclassified on the basis of the total number of attempts at withdrawing from
      alcohol (including the medically supervised) only the deficit in the vigilance
      task was associated with the number of withdrawal attempts. The effects of
      medically supervised detoxifications on maze 1 and vigilance task were confounded
      with other factors related to the history of alcoholism, alcohol use, age of
      starting heavy drinking and years of problem drinking. CONCLUSIONS: Repeated
      experience of withdrawal from alcohol is thus associated with impaired cognitive
      function although it appears that for some of these effects, other factors
      associated with the history of alcoholism might also be involved.

PMID- 14574227
TI  - Dopamine activity in the nucleus accumbens during consummatory phases of oral
      ethanol self-administration.
AB  - BACKGROUND This present study was designed to clarify the role of dopamine in the
      nucleus accumbens during operant ethanol self-administration by separating bar
      pressing (ethanol seeking) from ethanol consumption. Furthermore, we sought to
      define the relationship between ethanol in the brain and the accumbal dopamine
      response after oral self-administration of ethanol. METHODS: Two separate groups
      of male Long-Evans rats were trained to bar press with 10% ethanol or water. Rats
      were trained to elicit an escalating number of bar presses across daily sessions
      before gaining access to the drinking solution for 20 min. Microdialysis was
      performed before (during a waiting period), during, and after bar pressing and
      drinking. A handling control group was included, but did not receive training.
      RESULTS: A significant increase in dopamine occurred during placement of the rats
      into the operant chamber in trained rats and handling controls. The lever
      pressing period did not produce an increase in dialysate dopamine. Accumbal
      dopamine was increased in the first 5 min of ethanol, but not water, consumption.
      Ethanol appeared in the dialysate sample following ethanol availability, and peak
      concentrations were reached at 10 min. Most of the ethanol and water consumption
      occurred within 5 min of fluid access. The probes were distributed in the core
      (32%), shell (32%), and core plus shell (36%) regions of the nucleus accumbens.
      CONCLUSIONS: The enhancement of dopamine during transfer into the operant chamber
      does not depend on anticipation or operant training with ethanol or water
      reinforcement. Furthermore, the difference between the time course of accumbal
      dopamine and ethanol in dialysates suggests that the dopamine response is not
      solely due to pharmacological effects of ethanol. The dopamine response may be
      associated with the stimulus properties of ethanol presentation, which would be
      strongest during consumption.

PMID- 14574228
TI  - Reinforcement from pharmacological effects of ethanol in newborn rats.
AB  - BACKGROUND: The preweanling period in the rat is characterized by acceptance of
      substantial amounts of ethanol and susceptibility to its reinforcing effects. It
      has been unclear, however, whether the neurobiological basis of ethanol
      reinforcement properties at this age is in ethanol's olfactory, gustatory, or
      pharmacological effects. METHODS: The effectiveness of intraperitoneal (ip)
      ethanol as a reinforcer for newborn (3-hr-old) rats was tested toward separation
      of the orosensory and pharmacological sources of ethanol reinforcement.
      Responsiveness to a test nipple by pups given such pairings was compared with
      that of pups given unpaired presentations of the nipple and ethanol. RESULTS:
      Reinforcement was assessed in terms of response to a surrogate nipple 1 hr after
      a single pairing of a similar nipple providing water (conditioned stimulus) and
      ip injection of ethanol (0.125, 0.25, 0.50, or 0.75 g/kg; unconditioned
      stimulus). Significant effects of ethanol reinforcement occurred with the lower
      doses (0.125 and 0.25 g/kg); higher doses of ethanol (0.50 and 0.75 g/kg) had no
      significant reinforcement effect. A second experiment determined that for
      conditioning with ip ethanol as the unconditioned stimulus, a conditioned
      stimulus consisting of only ingesting water or only suckling on an empty nipple
      also yielded significant reinforcing effects of ethanol, although with less
      strength than their combination. Both reinforcing doses of ethanol, 0.125 and
      0.25 g/kg, yielded detectable concentrations of ethanol in the blood 5 min after
      injection, which were sustained at a significantly lower level 60 min after
      administration. CONCLUSIONS: These data indicate that aside from possible, and
      likely weak, hematogenic sources of gustatory and olfactory attributes of
      ethanol, the basis of ethanol's reinforcement effect in neonatal rats is
      primarily pharmacological. For the pharmacological effects of ethanol to be
      reinforcing for the neonatal rat, concurrent appetitive activity on a nipple
      providing a fluid may be necessary for a substantial effect with this paradigm.

PMID- 14574229
TI  - Pavlovian conditioning with ethanol: sign-tracking (autoshaping), conditioned
      incentive, and ethanol self-administration.
AB  - BACKGROUND: Conditioned incentive theories of addictive behavior propose that
      cues signaling a drug's reinforcing effects activate a central motivational
      state. Incentive motivation enhances drug-taking and drug-seeking behavior. We
      investigated the behavioral response to cues associated with ethanol and their
      interaction with operant self-administration of ethanol. METHODS: In two
      experiments, rats received operant training to press a lever for a sweetened
      ethanol solution. After operant training, the animals were given Pavlovian
      pairings of a brief and localized cue light with the sweetened ethanol solution
      (no lever present). Lever pressing for ethanol was then re-established, and the
      behavioral effects of the cue light were tested during an ethanol self
      administration session. RESULTS: The conditioned responses resulting from pairing
      cue lights with the opportunity to ingest ethanol had three main effects: (1)
      induction of operant behavior reinforced by ethanol, (2) stimulation of ethanol
      seeking behavior (magazine entries), and (3) signal-directed behavior (i.e.,
      autoshaping, or sign-tracking). Signal-directed behavior interacted with the
      other two effects in a manner predicted by the location of the cue light. These
      conditioned responses interact with operant responding for ethanol reinforcement.
      CONCLUSIONS: These findings demonstrate the importance of Pavlovian conditioning
      effects on ethanol self-administration and are consistent with conditioned
      incentive theories of addictive behavior.

PMID- 14574230
TI  - Cellular adaptation to chronic ethanol results in altered compartmentalization
      and function of the scaffolding protein RACK1.
AB  - BACKGROUND: Previously, we found that acute ethanol induces the translocation of
      the scaffolding protein RACK1 to the nucleus. Recently, we found that nuclear
      RACK1 mediates acute ethanol induction of immediate early gene c-fos expression.
      Alterations in gene expression are thought to lead to long-term changes that
      ultimately contribute to the development of alcohol addiction and toxicity.
      Therefore, we sought to determine the effects of chronic exposure of cells to
      ethanol on the cellular compartmentalization of RACK1 and on c-fos messenger RNA
      (mRNA) and protein expression. METHODS: Rat C6 glioma cells were used as the cell
      culture model. Immunohistochemistry was implemented to visualize the localization
      of RACK1 and to monitor the protein level of c-fos. Reverse-transcription
      polymerase chain reaction was used to measure c-fos mRNA levels. The Tat-protein
      transduction method was used to transduce recombinant Tat-RACK1 into cells as
      previously described. RESULTS: Chronic exposure of cells to 200 mM ethanol for 24
      and 48 hr resulted in the gradual re-distribution of RACK1 out of the nucleus. It
      is interesting to note that acute ethanol re-challenge immediately after chronic
      treatment did not result in RACK1 translocation to the nucleus, and nuclear
      compartmentalization of RACK1 in response to acute ethanol was detected only
      after 24 hr of withdrawal. Similar patterns were obtained for c-fos expression.
      Chronic exposure to ethanol did not result in an increase in mRNA or protein
      levels of c-fos. Furthermore, acute ethanol exposure did not increase c-fos
      protein levels in cells that were first treated chronically with ethanol.
      However, transduction of exogenous RACK1 expressed as a Tat-fusion protein was
      able to rescue c-fos mRNA expression after chronic ethanol exposure. CONCLUSIONS:
      Our data suggest that RACK1 nuclear compartmentalization and ethanol-induced c
      fos expression are transient and are desensitized to ethanol during prolonged
      exposure to high concentrations. The desensitization is temporary, and RACK1 can
      respond to acute ethanol treatment after a 24-hr withdrawal period. Our data
      further suggest that the altered compartmentalization of RACK1 leads to
      differences in c-fos expression upon acute or chronic exposure to ethanol. In
      summary, RACK1 is an important molecular mediator of the acute and chronic
      actions of ethanol on the expression of c-fos. These findings could have
      implications for the molecular signaling pathways leading to pathologic states
      associated with alcoholism, including toxicity.

PMID- 14574231
TI  - Chronic intermittent injections of high-dose ethanol during adolescence produce
      metabolic, hypnotic, and cognitive tolerance in rats.
AB  - BACKGROUND: Many humans are first exposed to ethanol during adolescence, the time
      at which they are most likely to binge drink ethanol. Chronic intermittent
      ethanol (CIE) exposure produces ethanol tolerance in adolescent rodents. Recent
      studies suggested that adolescent animals administered CIE experienced increased
      cognitive impairment following an ethanol challenge. These studies further
      explore development of ethanol tolerance caused by CIE in adolescence, and
      whether CIE during adolescence leads to altered ethanol response in adulthood.
      METHODS: Beginning postnatal day (P) 30, adolescent rats were administered 5.0
      g/kg ethanol or saline every 48 hours for 20 days. In experiment I, animals were
      tested for differential weight gain. In experiment II, loss of righting reflex
      (LORR) was observed after each injection, then at completion of pretreatment all
      animals were tested with 5.0 g/kg ethanol and LORR was observed. In experiment
      III, blood ethanol levels were observed and elimination rates calculated after
      the first and fifth pretreatments. All animals were tested with 5.0 g/kg at
      completion of pretreatment and elimination rates were recalculated. In experiment
      IV, animals were trained on the spatial version of the Morris Water Maze Task
      (MWMT) on non-treatment days. Following completion of pretreatment and training,
      animals were tested after receiving an ethanol (1.0, 1.5, or 2.0 g/kg), or
      saline. Tests for experiments II, III, and IV were repeated in the same animals
      following 12 ethanol-free days. RESULTS: Chronic intermittent ethanol exposure
      during adolescence caused differential weight gain (experiment I). Adolescent
      rats developed tolerance to ethanol-induced LORR (experiment II) and metabolic
      tolerance to ethanol (experiment III). This tolerance was seen after 12 ethanol
      free days. CIE also attenuated ethanol-induced spatial memory deficits in the
      MWMT (experiment IV). This effect was not long-lasting. CONCLUSIONS: Following
      CIE pretreatment during adolescence, tolerance developed to the hypnotic and
      cognitive impairing effects of ethanol, along with increased metabolic rate and
      decreased weight gain. These results further emphasize the ability of CIE to
      produce a variety of effects during adolescence, some having long-lasting
      consequences.

PMID- 14574233
TI  - Ethanol decreases natural killer cell activation but only minimally affects
      anatomical distribution after administration of polyinosinic:polycytidylic acid:
      role in resistance to B16F10 melanoma.
AB  - BACKGROUND: Natural killer (NK) cells are critical in resistance to B16F10 lung
      metastases in B6C3F1 mice. Activation of NK cells by polyinosinic:polycytidylic
      acid (poly I:C; 0.1 mg, intraperitoneally) increases resistance to B16F10 cells.
      This effect is reduced after administration of ethanol (EtOH; 6 g/kg by oral
      gavage). The present study was conducted to determine whether decreased
      resistance is due to alteration of the distribution and/or the activation of NK
      cells. METHODS: These parameters were measured in the spleen, lungs, and
      peripheral blood 4 and 12 hr after EtOH and poly I:C administration. For
      assessing the time after poly I:C administration during which NK cells are
      important in resistance to B16F10 cells, anti-NK1.1 antibody was used to deplete
      NK cells in vivo 48 hr before and 0, 6, 12, and 24 hr after intravenous injection
      of B16F10 tumor cells. RESULTS: Depletion of NK cells at any time up to 12 hr
      after B16F10 administration significantly increased the number of tumor nodules
      in the lungs, but depletion at 24 hr had a smaller effect. Flow cytometry
      revealed that there was a small but significant increase in the percentage of NK
      cells in the lungs at 12 hr, which was not changed by EtOH. Corresponding NK cell
      lytic function in the lungs was increased significantly at both 4 and 12 hr by
      poly I:C. However, the increase was not significantly different from the naive
      control value at 4 hr in mice treated with poly I:C plus EtOH, indicating that
      EtOH decreased activation of NK cells in the lungs at 4 hr. In the spleen, no
      treatment significantly altered the percentage of NK cells at 4 or 12 hr.
      However, poly I:C significantly enhanced lytic function, and this enhancement was
      suppressed by EtOH (by approximately 50%). In the blood, the only significant
      change in NK cell percentage or lytic activity was an increase in the percentage
      of NK cells at 12 hr, which was equivalent in the poly I:C and the poly I:C plus
      EtOH groups. CONCLUSIONS: These results demonstrate that EtOH partially abrogates
      the poly I:C-induced enhancement of resistance to B16F10 cells and that decreased
      activation of NK cells in the lungs at a critical time early in the response to
      poly I:C may contribute to this effect. Other parameters could also contribute,
      but there was little support for an important role for changes in NK cell
      distribution.

PMID- 14574232
TI  - Binding of acetaldehyde to a glutathione metabolite: mass spectrometric
      characterization of an acetaldehyde-cysteinylglycine conjugate.
AB  - BACKGROUND: Ethanol administration decreases hepatic glutathione levels and
      increases urinary sulfhydryl excretion. Ethanol-induced liver injury is blunted
      by the administration of glutathione precursors. Acetaldehyde generated in the
      metabolism of ethanol binds to a number of amino acid residues in proteins and
      peptides, but it does not react readily with glutathione. Due to the possible
      role of acetaldehyde in cysteine and glutathione homeostasis, we investigated the
      reaction of acetaldehyde to cysteinylglycine, the dipeptide generated in vivo in
      the hydrolysis of glutathione by gamma-glutamyltransferase. METHODS: A conjugate
      between acetaldehyde and cysteinylglycine was generated under physiologically
      relevant conditions, both in vitro and in vivo. It was separated by a new reverse
      phase high-performance liquid chromatography method and identified by
      electrospray ionization/ion trap tandem mass spectrometric analysis. RESULTS: The
      conjugate with a stoichiometry of 1:1 between cysteinylglycine and acetaldehyde
      is most rapidly generated in vitro and was identified by mass spectroscopy as 2
      methyl-thiazolidine-4-carbonyl-glycine. This thiazolidine derivative is stable in
      vitro and in biological fluids of rats. The conjugate was present in high
      concentrations in the bile of rats pretreated with ethanol and an inhibitor of
      aldehyde dehydrogenase. CONCLUSIONS: The sequestering of cysteinylglycine by
      acetaldehyde occurs rapidly under physiologic conditions. Long-lived sulfur
      containing biomolecules that incorporate acetaldehyde might affect cysteine and
      glutathione homeostasis and may also play a protective role by reducing
      circulating acetaldehyde levels. The acetaldehyde conjugate or its metabolic
      products could potentially serve as markers of ethanol consumption.

PMID- 14574234
TI  - Ethanol modulation of excitatory and inhibitory synaptic transmission in rat and
      monkey dentate granule neurons.
AB  - BACKGROUND: The physiological mechanisms underlying the behavioral and cognitive
      effects of ethanol are not fully understood. However, there is now compelling
      evidence that ethanol acts, at least in part, by modulating the function of a
      small group of proteins that mediate excitatory and inhibitory synaptic
      transmission. For example, intoxicating concentrations of ethanol have been shown
      to enhance GABAergic synaptic inhibition and depress glutamatergic excitatory
      neurotransmission in a number of brain regions. Because all of these
      electrophysiological studies have been performed in rodent brain slice or
      neuronal culture preparations, direct evidence that ethanol exerts similar
      effects on synaptic transmission in the primate central nervous system is
      lacking. METHODS: We have therefore developed methods to perform patch-clamp
      electrophysiological recordings from neurons in acutely prepared monkey (Macaca
      fascicularis) hippocampal slices. We have used these methods to compare the acute
      effects of ethanol on excitatory and inhibitory synaptic transmission in rat and
      monkey dentate granule neurons. RESULTS: Under our recording conditions, ethanol
      significantly potentiated gamma-aminobutyric acid type A inhibitory postsynaptic
      currents in both rat and monkey neurons. In addition, ethanol significantly
      inhibited NMDA, but not AMPA, excitatory postsynaptic currents in dentate granule
      neurons from both species. Notably, no significant differences were observed in
      any of the pharmacological properties of inhibitory or excitatory synaptic
      responses recorded from rat and monkey neurons. CONCLUSIONS: These data suggest
      that the differences in the behavioral effects of ethanol that have been observed
      between rats and higher-order mammals, such as monkeys and humans, may not
      reflect differences in the sensitivity of some of the major synaptic sites of
      ethanol action. Moreover, our results provide empirical evidence for the use of
      rodent brain slice preparations in elucidating synaptic mechanisms of ethanol
      action in the primate central nervous system.

PMID- 14574235
TI  - Distinct regions of the slo subunit determine differential BKCa channel responses
      to ethanol.
AB  - BACKGROUND: Ethanol at clinically relevant concentrations increases BKCa channel
      activity in dorsal root ganglia neurons, GH3 cells, and neurohypophysial
      terminals, leading to decreases in cell excitability and peptide release. In
      contrast, ethanol inhibits BKCa channels from aortic myocytes, which likely
      contributes to alcohol-induced aortic constriction. The mechanisms that determine
      differential BKCa channel responses to ethanol are unknown. We hypothesized that
      nonconserved regions in the BKCa channel-forming subunit (slo) are major
      contributors to the differential alcohol responses of different BKCa channel
      phenotypes. METHODS: We constructed chimeras by interchanging the core and the
      tail domains of two BKCa channel-forming subunits (mslo and bslo) that, after
      expression, differentially respond to ethanol (activation and inhibition,
      respectively), and studied ethanol action on these mbslo and bmslo chimeric
      channels using single-channel, patch-clamp techniques. RESULTS AND CONCLUSION:
      Data from cell-free membranes patches demonstrate that the activity of channels
      that share a mslo-type core-linker (wt mslo and the mbslo chimera) is
      consistently and significantly potentiated by acute exposure to ethanol. Thus, a
      mslo tail is not necessary for ethanol potentiation of slo channels. In contrast,
      the activity of channels that share a bslo-type core-linker (wt bslo and the
      bmslo chimera) display heterogenous responses to ethanol: inhibition (in the
      majority of cases), refractoriness, or activation. Overall, our data indicate
      that the slo core-linker is a critical region likely contributing to the
      differential responses of BKCa channels to ethanol.

PMID- 14574236
TI  - Treatment of alcohol abuse: an evidence-based review.
AB  - This article represents the proceedings of a symposium at the 2002 annual meeting
      of the Research Society on Alcoholism in San Francisco, CA, organized and
      cochaired by Mats Berglund and Sten Thelander. The presentations were (1)
      Preventive interventions against hazardous consumption of alcohol, by Mikko
      Salaspuro; (2) Treatment of alcohol withdrawal, by Johan Franck; (3) Psychosocial
      treatment for alcohol problems, by Sven Andreasson and Agneta Ojehagen; and (4)
      Pharmacological treatment of alcohol dependence, by Mats Berglund.

PMID- 14574237
TI  - Measuring outcome in interventions for alcohol dependence and problem drinking:
      executive summary of a conference sponsored by the national institute on alcohol
      abuse and alcoholism.

PMID- 14574238
TI  - Assessing drinking outcomes in alcohol treatment efficacy studies: selecting a
      yardstick of success.
AB  - BACKGROUND: Although the number of alcohol treatment efficacy trials has
      mushroomed, there is no consensus on how best to measure outcomes. To advance the
      goal of establishing cross-trial consistency in measuring outcomes in clinical
      efficacy studies, the National Institute on Alcohol Abuse and Alcoholism convened
      a panel of experts and charged them with exploring, debating, and, ultimately,
      selecting a "sentinel" or "optimal" outcome measure to be used in future alcohol
      treatment studies. The goal of this article, one in a series of several presented
      at the National Institute on Alcohol Abuse and Alcoholism conference, is to
      discuss (1) the rationale underlying selection of an optimal outcome measure, (2)
      the necessary characteristics of an optimal outcome measure, (3) the utility of
      selecting an optimal measure, and (4) which drinking assessment methods could be
      used to collect data to portray the optimal outcome measure. METHODS: At a
      minimum, the criteria for an "optimal" measure include that it be
      psychometrically sound. In addition, it should have considerable currency in the
      field, thereby increasing its prospects for adoption. The measure should also be
      consistent with the concepts of greatest interest and relevance to the field
      (e.g., directly reflect the fundamental goal of alcohol treatment). In light of
      these highly desired features, percent of days heavy drinking was chosen at the
      conference as a practical and relevant measure of alcohol treatment outcome.
      CONCLUSIONS: Percent of days heavy drinking should be the optimal measure of
      alcohol treatment outcome. Currently, daily drinking estimation methods are the
      most useful for gathering data that can reflect the optimal measure. In addition,
      data gathered by daily drinking estimation methods can be used to study a variety
      of other outcome variables of interest to clinical researchers.

PMID- 14574239
TI  - Recommendations on use of biomarkers in alcoholism treatment trials.
AB  - BACKGROUND: Biochemical markers of heavy drinking are playing increasingly
      prominent roles in alcohol treatment efficacy studies, especially in those
      designed to evaluate medications. Among these roles are serving as inclusion or
      exclusion criteria for research participants, corroboration of self-report of
      drinking status, assessment of the safety of the agent being evaluated, and
      determination of treatment outcome. METHODS: Recent alcohol medication
      development trials that included biomarker information were reviewed and
      critiqued from the perspectives of how biomarker measures were used and how
      findings on them were reported. RESULTS: Although generally the application of
      biomarkers as inclusion criteria is not recommended, they may aid in exclusion of
      potential subjects (e.g., elevated liver function measures in trials of agents
      that could result in liver damage). Biomarkers are most commonly used as
      indicators of outcome, usually serving as secondary outcome variables. The
      relationship of outcome findings on biomarker and self-report measures is
      positive, but only moderate. As used to date, biomarkers of drinking tend to be
      less sensitive than well-standardized and properly administered self-report
      measures. Nevertheless, they do provide a useful, unique source of information on
      drinking status. CONCLUSIONS: The contribution of biomarkers to alcoholism
      clinical research would be enhanced if certain design strategies were
      incorporated into their application and if critical information were included in
      the research publication. This article offers a series of recommendations to
      improve on their use in a research context.

PMID- 14574240
TI  - Outcome variables and their assessment in alcohol treatment studies: 1968-1998.
AB  - BACKGROUND: This article provides a historical overview of the assessment of
      outcome variables in alcohol treatment studies that were first published between
      1968 and 1998. The review focuses on changes over time in (1) the number of
      outcome variables and the number of different types of outcome variables
      assessed, (2) the likelihood of assessing specific types of outcome variables,
      (3) the methods used to assess outcome variables, and (4) the status of outcome
      assessment in more recent studies first published between 1990 and 1998. METHODS:
      Reports of 357 alcohol treatment trials with two or more treatment/control groups
      were coded with respect to the number and types of outcome variables assessed,
      sources of outcome data, and methodological aspects of outcome assessment.
      RESULTS: Although the number of outcome variables assessed in studies, on
      average, did not increase significantly over time, the number of different types
      of outcome variables did increase. An expected decrease in the assessment of
      categorical abstinence was not found, but another categorical variable, global
      ratings of drinking improvement, did decrease over time. More recent studies were
      more likely to assess such continuous variables as time abstinent, alcohol
      consumption, time drinking, dependence symptoms, and drinking-related problems.
      Physiological markers of drinking/alcohol misuse also were assessed more
      frequently in later years. Some aspects of outcome assessment methods exhibited
      improvement over time; validity data were more likely to be provided or cited,
      and self-reports of drinking behaviors were more likely to be corroborated in
      studies first published in more recent years. However, the percentages of studies
      that provided/cited reliability data for outcome measures, indicated that follow
      up data collectors were not affiliated with treatment and were unaware of
      respondents' treatment conditions, and reported that respondents were alcohol
      free at follow-up did not rise significantly over time. CONCLUSIONS: Although the
      methods of outcome assessment improved between 1968 and 1998, much room for
      improvement remains.

PMID- 14574241
TI  - Clinical and methodological utility of a composite outcome measure for alcohol
      treatment research.
AB  - BACKGROUND: How to capture different response patterns resulting from alcohol
      treatment has been a troublesome issue for alcohol researchers. A composite
      measure is one approach to capturing multiple treatment outcomes among diverse
      client populations. This article provides the rationale, development, and work
      conducted thus far on the composite outcome index and discusses the clinical
      utility of the measure. METHODS: With the use of Project MATCH data, the
      composite outcome measure was examined in relation to self-reported alcohol
      consumption and alcohol problems and biological markers as well as in relation to
      other areas of functioning, such as psychiatric dysfunction and quality of life.
      Also, for assessing the stability of the measure, different composite outcomes
      statuses were assessed over time. RESULTS: Individuals with better scores on
      composite outcome index had fewer percent days abstinent, consumed more alcohol
      when they drank, had a greater number of alcohol problems, and evidenced higher
      blood levels as measured by gamma-glutamyltranspeptidase and carbohydrate
      deficient transferrin. Individuals with poorer composite outcome statuses had
      poorer social and behavioral role functioning and mental and physical health
      related quality of life. Findings on short- and long-term composite outcome
      statuses revealed that only a minority of clients (30%) sustained a remitted
      status (i.e., abstinent or moderate drinking without problems) over the 1-year
      follow-up, and fully 70% of the clients had reached a nonremitted status (i.e.,
      heavy drinking and/or problems) on the composite measure at one or more time
      points during the 12-month follow-up. CONCLUSIONS: The composite outcome index
      could be used usefully along with singular measures of consumption to obtain a
      more complete picture of what has occurred among clients posttreatment. Future
      work will involve the testing of the composite outcome index with other client
      populations and/or different treatments to further our understanding of the
      varying response patterns found among alcohol-dependent clients.

PMID- 14574242
TI  - Methodological and statistical considerations in measuring alcohol treatment
      effects.
AB  - This article addresses the design and selection of outcome methods for treatment
      research from a statistical perspective. Two of the major statistical and
      methodological issues relevant to the selection of dependent variable(s) are
      statistical power and social utility. Power is the paramount issue in research
      design. Power can be improved by measures and methods tailored to the predicted
      effects of treatment. These effects should vary from treatment to treatment,
      suggesting that no single outcome measure is suitable for all purposes. In
      estimating power, researchers should also consider the time-varying nature of
      most types of treatment effects. Given these considerations, timeline procedures
      have advantages because they allow the derivation of measures linked to specific
      treatment components. They also permit the study of time-varying effects of
      variables such as life stress. An analysis on the relationship between drinking
      and self-reported stress is presented as an illustration of how advanced
      statistical methods, in conjunction with carefully gathered data, can provide
      process data on how treatment can affect individual responses to stressors or
      other events. From a social utility perspective, however, having research focus
      on narrower and narrower slices of behavior in the search for power raises
      questions about the value of this research to clients and society. For dealing
      with this dilemma, it will be necessary to build a series of studies linking
      improvement in specific aspects of short-term outcome to longer term outcome and
      ultimately benefit to society.

PMID- 14574243
TI  - Continuing medical education review: choroidal neovascularization in age-related
      macular degeneration--what is the cause?

PMID- 14574244
TI  - Perfluorocarbon liquid utilization in primary vitrectomy repair of retinal
      detachment with multiple breaks.
AB  - PURPOSE: To evaluate the efficacy of pars plana vitrectomy in conjunction with
      intraoperative perfluoro-n-octane (PFO) use as initial treatment of retinal
      detachment (RD) with multiple breaks located at various distances from the ora
      serrata. METHODS: Twenty-two consecutive eyes (15 phakic, 2 aphakic, and 5
      pseudophakic) presenting with RD with multiple breaks and tears underwent primary
      pars plana vitrectomy, PFO retinal reattachment, transcleral cryopexy or
      endolaser treatment of breaks, PFO/air exchange, and final injection of 18%
      perfluoropropane (C3F8). Scleral buckles were not used. The mean follow-up period
      was 29 months. RESULTS: Temporary PFO utilization attached the posterior retina
      and facilitated the safe removal of vitreous at its base and around the retinal
      tears. Intraoperative complications included new breaks (3 eyes), enlargement of
      breaks (2 eyes), and a small bubble of subretinal PFO (1 eye). Postoperatively,
      the retina remained attached during follow-up in 19 eyes. Cataract developed or
      progressed in 13 phakic eyes. CONCLUSIONS: Pars plana vitrectomy in conjunction
      with intraoperative PFO utilization is effective as initial treatment of RDs with
      multiple breaks. The main limitation of this technique is the postoperative
      progressive cataract formation in phakic eyes.

PMID- 14574245
TI  - Management of giant retinal tears with vitrectomy, internal tamponade, and
      peripheral 360 degrees retinal photocoagulation.
AB  - PURPOSE: To determine the effectiveness of vitrectomy, internal tamponade, and
      peripheral 360 degrees retinal photocoagulation in the management of giant
      retinal tears (GRTs). PARTICIPANTS: Eighteen eyes of 18 consecutive patients with
      GRTs were operated on at Jules Gonin Eye Hospital between 1992 and 1999. None of
      them had previous vitreoretinal surgery. METHODS: Eyes in the series underwent
      pars plana vitrectomy, perfluorocarbon liquid and silicone oil (17 eyes) or gas
      (one eye) exchange, and retinopexy. Retinopexy was applied to the edges of the
      tear using photocoagulation, and it was extended over 360 degrees to the
      peripheral attached retina. No scleral buckle was placed, even if proliferative
      vitreoretinopathy (PVR) was present. RESULTS: The GRT was 180 degrees or greater
      in seven eyes and 90 degrees to 180 degrees in 11 eyes. The lower edge of the GRT
      was located in an inferior quadrant in 15 eyes. PVR was grade A in seven eyes,
      grade B in eight eyes, and grade C in three eyes. In the last three eyes, PVR was
      anterior (C-A9, Patient 4) and posterior (C-P6 subretinal, Patient 11; C-P3,
      Patient 13). In 16 (88.8%) of the 18 eyes, the retina was successfully reattached
      after surgery, and silicone oil was removed after a mean period of 7.7 weeks. In
      the other two eyes, the retina remained detached or redetached despite the
      silicon oil tamponade. One of these two eyes underwent three further surgeries,
      but the retina did not reattach. The other eye was successfully reoperated on
      with an encircling and radial scleral buckle, and silicone oil was removed later.
      At the end of the follow-up, the retina was attached in 17 (94.4%) of the 18
      eyes. The mean follow-up was 28.6 months (range, 4.5-73 months). CONCLUSIONS: The
      success rate of management of GRTs with vitrectomy, internal tamponade, and
      peripheral 360 degrees photocoagulation of the retina without scleral buckle is
      high. Photocoagulation of the peripheral retina over 360 degrees appears to
      decrease the risk of secondary peripheral retinal tears.

PMID- 14574246
TI  - Refractive changes following scleral buckling surgery in juvenile retinal
      detachment.
AB  - PURPOSE: To examine the effects of scleral buckling on the eye growth of children
      after retinal detachment repair according to the degree of refractive change.
      METHODS: Thirty-five eyes of 35 patients (mean age, 11.5 years; range, 7-15
      years) were treated using a silicone implant scleral buckling procedure.
      Postoperative refractive change in the treated eyes was analyzed statistically,
      with the fellow eyes used as controls. The effects of age at the time of surgery,
      length of the silicone tire, postoperative visual acuity, and postoperative
      refraction were also examined. RESULTS: The mean refractive change in treated
      eyes from 1 to 4 years after the procedure was -0.6 diopter (D), whereas the mean
      change in fellow eyes was -1.3 D. The treated eyes became less myopic than the
      fellow eyes (P=0.024), particularly in patients younger than 10 years (-0.1 D
      versus -1.6 D, respectively; P=0.003) or when the scleral buckle extended beyond
      two quadrants (-0.4 D versus -1.3 D, respectively; P=0.020). CONCLUSIONS: Scleral
      buckling resulted in significantly less myopia, particularly in younger patients
      and in those receiving longer buckling tires. This finding suggests that scleral
      buckling in children might impede ocular growth.

PMID- 14574247
TI  - Scleral buckling: implant versus explant.
AB  - PURPOSE: To compare the implant and explant techniques of scleral buckling.
      METHODS: This prospective, randomized clinical study compared the two techniques
      of scleral buckling. Variables such as size and extent of the buckle, duration of
      the surgery, complications, and anatomical and visual outcome were studied. The
      height of the buckle as measured by ultrasonography was also studied. RESULTS: No
      significant difference was found between the two groups for total duration of the
      surgery, complications, anatomical results, visual outcome, and buckle height.
      For the 1- to 2-quadrant buckles, duration of the surgery up to initiation of
      subretinal fluid drainage was found to be significantly shorter for the explant
      group. Serial ultrasonography showed significant reduction in buckle height over
      6 months in both groups to an equal degree. CONCLUSIONS: Scleral buckling seems
      to be equally effective whether performed as an implant or explant.

PMID- 14574248
TI  - Late swelling and removal of Miragel buckles: a comparison with silicone
      indentations.
AB  - BACKGROUND: To describe the indications for removal of Miragel episcleral buckles
      and to compare them with removed silicone sponges and solid silicone
      indentations. METHODS: Retrospective analysis of the charts of patients
      successfully treated for retinal detachment in whom the episcleral buckle was
      removed after surgery, with a minimal follow-up of 6 months. RESULTS: In a series
      of 90 eyes of 90 patients, including 38 cases of Miragel elements, 25 cases of
      solid silicone, and 27 cases of silicone sponge removal, the duration of
      indentation before removal was significantly longer with Miragel (91.9 months)
      than with solid silicone (10.6 months) and silicone sponges (18.6 months). In
      eyes treated with Miragel elements, swelling of the material with progressive
      limitation of ocular motility and protrusion of the buckle beneath the eyelids
      indicated its removal in 34 (89.5%) eyes. Infection of the buckle and erosion of
      the conjunctiva with an exposed indentation were significantly more common with
      silicone buckles. Overall, scleral perforation occurred in four (4.4%) eyes, and
      retinal redetachment occurred in eight (8.8%) eyes. CONCLUSION: Late swelling of
      Miragel buckling elements represents a common indication for buckle removal,
      significantly different from silicone indentations.

PMID- 14574249
TI  - Cataract surgery and silicone oil removal: visual outcome and complications in a
      combined vs. two step surgical approach.
AB  - PURPOSE: To compare visual outcome and complications of two surgical strategies
      for patients who needed cataract surgery and silicone oil removal. METHODS: A
      prospective, nonrandomized study was performed to compare two groups of patients
      who had cataract surgery and silicone oil removal from April 1998 to January
      2002. From April 1998 to November 1999, patients had two surgical sessions with
      cataract surgery before silicone oil removal (Group 1), and from December 1999 to
      January 2002, patients underwent combined cataract surgery and silicone oil
      removal in a single session (Group 2). RESULTS: Thirty-five patients were
      included in each group. The postoperative visual acuity improved by at least two
      lines of Snellen in 13 patients (37.1%) in Group 1 and 15 (42.8%) patients in
      Group 2 (P=0.63). The mean visual improvement was 0.12 lines and 0.13 lines in
      groups 1 and 2 (P=0.62). Complications in groups 1 and 2 included transient
      intraocular pressure rise (25.7% versus 28.5%), retinal detachment (14.2% versus
      11.4%), fibrin reaction (5.7% in both groups), and persistent intraocular
      pressure rise (2.8% in both groups). CONCLUSION: The visual outcome and
      complication rates were similar in both groups. Combined surgery offers the
      advantages of a single surgical event and a faster visual rehabilitation. We
      therefore suggest a surgical approach with combined cataract surgery and silicone
      oil removal in selected patients with a stable retinal situation.

PMID- 14574250
TI  - Vitrectomy for posterior segment intraocular foreign bodies: visual results and
      prognostic factors.
AB  - PURPOSE: To evaluate the visual results and determine the prognostic factors
      after the removal of retained posterior segment intraocular foreign bodies
      (IOFBs) by pars plana vitrectomy. METHODS: A retrospective study of 40
      consecutive cases of pars plana vitrectomy for the removal of IOFBs during the
      period of January 1991 to June 2000 was conducted. Association between visual
      outcome and various preoperative, operative, and postoperative variables was
      statistically analyzed. RESULTS: Of the 40 cases available for the study, the
      IOFBs could be removed in 36 eyes. Half the patients had removal of the IOFB
      within 14 days of the injury. Nineteen patients (47.5%) achieved a visual acuity
      of 20/40 or better. Postoperative retinal detachment occurred in 13 patients
      (32.5%). Poor visual outcome was found to be significantly associated with poor
      initial visual acuity and postoperative retinal detachment, whereas good visual
      outcome was significantly associated with the absence of lens injury and absence
      of postoperative retinal detachment. CONCLUSIONS: Acceptable visual results could
      be achieved after the removal of posterior segment IOFBs by vitrectomy, despite a
      delay in surgery. Postoperative retinal detachment, poor initial visual acuity,
      and the absence of lens injury were the factors that played a significant role in
      determining the visual outcome.

PMID- 14574251
TI  - A new instrument for drainage or injection of fluid within subretinal space.
AB  - PURPOSE: To describe a new instrument, the subretinal aspiration and injection
      device (SR-AID), designed to facilitate the controlled external drainage or
      injection of fluid in the subretinal space. METHODS: The SR-AID is formed by an
      assembly of a probe, handle body, and a driving unit. The curved conduit within
      the probe segment forms a curved tunnel and acts as a guide along which a needle
      moves back and forth. The feasibility of fluid injection beneath the attached
      retina was tested in animal eyes. The efficacy of subretinal fluid drainage with
      the SR-AID were assessed in six cases of clinical retinal detachment. RESULTS:
      External approach to the subretinal space under ophthalmoscopic monitoring can be
      achieved by oblique angle penetration of the scleral wall with a needle from the
      SR-AID. Fluid was injected successfully into the subretinal space in three of six
      rabbit eyes and in two of two pig eyes. The mean duration required for the
      drainage of subretinal fluid with the SR-AID was 127 seconds. There was no
      incidence of significant subretinal hemorrhage or retinal perforation in the
      animal experiments and in human cases. CONCLUSION: Our case series suggests that
      the SR-AID provides an efficient and safe means of access to the subretinal
      space.

PMID- 14574252
TI  - Self-stabilizing wide-angle contact lens for vitreous surgery.
AB  - PURPOSE: To describe a new self-stabilizing modification for the wide-angle
      contact lens for vitreoretinal surgery. DESIGN: A standard wide-angle contact
      lens with the radius of curvature of 7.7 mm is modified with addition of four
      footplates to facilitate stability and centration. METHOD: A drop of viscoelastic
      material is placed between the lens and the cornea. This induces negative
      suction, which helps to retain the lens in position and allows dynamic viewing of
      the retina. CONCLUSION: This specially designed lens reduces the need for a
      skilled assistant to stabilize the contact lens. It provides a stable, well
      centered view of the peripheral fundus during vitreous surgery.

PMID- 14574253
TI  - von Hippel angioma in South Indian subjects--a clinical study.
AB  - PURPOSE: To assess the management strategies for retinal capillary hemangioma in
      von Hippel-Lindau disease. STUDY DESIGN: A retrospective, nonconsecutive case
      series of 12 patients. METHODS: We reviewed the records of patients diagnosed
      with retinal capillary hemangioma from January 1996 to June 2002. Age at
      diagnosis, visual acuity, tumor pattern and location, associated clinical
      features, type of treatment, and visual and anatomical outcomes were analyzed.
      RESULTS: None of the patients had evidence of extraocular hemangiomas. The
      patients were observed for 2 to 24 months. Ten of 12 hemangiomas were endophytic.
      Subretinal exudation was present in all patients. Cryotherapy was the most common
      treatment option with successful anatomical (7 of 8 patients) and visual (5 of 8
      patients) outcomes. Photocoagulation was successful in 1 of 2 patients. Two
      patients in the cryotherapy group and two in the photocoagulation group had
      complications, including macular scar, macular hole, epimacular membrane, and
      combined traction and rhegmatogenous retinal detachment. Two patients were lost
      to follow-up after cryotherapy. Seven of 10 patients with a minimum follow-up of
      2 months had improved visual acuity. CONCLUSIONS: Endophytic peripheral retinal
      capillary hemangioma with subretinal exudation was the commonest presentation in
      this series. Although cryotherapy and photocoagulation regress the tumor, these
      treatment modalities are associated with complications that may require surgical
      intervention. Retinal detachments in this group of patients are amenable to
      surgical intervention.

PMID- 14574254
TI  - Toxicity of indocyanine green injected into the subretinal space: subretinal
      toxicity of indocyanine green.
AB  - PURPOSE: To evaluate the toxicity of indocyanine green (ICG) injected into the
      subretinal space. Indocyanine green may come in contact with photoreceptors and
      retinal pigment epithelium through a macular hole during ICG-assisted peeling of
      the internal limiting membrane. METHODS: Balanced salt solution or ICG of various
      concentrations (0.6, 1.25, 2.5, or 5.0 mg/mL) was injected into the subretinal
      space of rabbit eyes and removed after 1 minute. After 3 days, 1 week, and 4
      weeks, the eyes were enucleated and evaluated by light microscopy and electron
      microscopy. RESULTS: When the ICG of 1.25 mg/mL or higher concentration was
      injected into the subretinal space, degenerative changes of the photoreceptors
      and the retinal pigment epithelial cells were found after 3 days with light and
      electron microscopy. After 1 week, the outer retina was disintegrated and the
      photoreceptors were not found. After 4 weeks in the eyes with 1.25 mg/mL ICG,
      short photoreceptors and a thin outer nuclear layer were seen. In the eyes with
      2.5 mg/mL or higher ICG, the photoreceptors and the outer nuclear layer were
      destroyed completely. CONCLUSION: The results of this study suggest that the ICG
      of 1.25 mg/mL or higher concentration has toxicity to the outer retina of the
      rabbit and may cause adverse effects on the functional outcome after macular hole
      surgery.

PMID- 14574255
TI  - New infusion cannula for prevention of retinal damage by infusion air during
      vitrectomy.
AB  - PURPOSE: Postoperative visual field defects are sometimes found after macular
      hole surgery. We have previously shown that damage to the retina by air infusion
      from an infusion cannula is a causative factor. To minimize such damage, we
      modified the infusion cannula and examined its effects experimentally. METHODS:
      An infusion cannula with a closed tip and openings on four sides was created.
      Experimentally, a vitrectomy was performed in rabbit eyes using this new infusion
      cannula or a conventional cannula. After fluid-air exchange at an air pressure of
      40 mmHg, eyes were removed and processed for histologic examination. The areas of
      the retinal damage caused by air infusion were evaluated. RESULTS: The area of
      retinal damage created by the new cannula was reduced significantly when compared
      with damage from conventional cannula use. CONCLUSION: This new cannula, designed
      for the purpose of scattering the air infusion, can reduce retinal damage, which
      leads to less frequent postoperative visual field defects.

PMID- 14574257
TI  - Transvitreal optic neurotomy for nonarteritic anterior ischemic optic neuropathy.
AB  - PURPOSE: To evaluate the role of transvitreal optic neurotomy in the treatment of
      nonarteritic anterior ischemic optic neuropathy, a scleral outlet compartment
      syndrome, in which neurovascular compression at the prelaminar and laminar
      regions of the optic nerve head may play a major role. METHODS: Seven eyes of
      seven selected patients with severe vision loss (<20/800) from nonarteritic
      anterior ischemic optic neuropathy underwent transvitreal nasal radial optic
      neurotomy. The study was not masked and not randomized. Visual acuity and visual
      fields, when possible, were measured, and fluorescein angiography was performed
      preoperatively and postoperatively. RESULTS: Four male and three female patients
      had a mean age of 52.4 years; five had bilateral disease. The mean follow-up was
      13 +/- 7 weeks. Mean preoperative visual acuity was 20/2400; mean postoperative
      visual acuity was 20/250, with an average of 10 lines of improvement. Six of
      seven patients showed visual improvement. One patient had peripapillary choroidal
      neovascularization. In two patients with sufficient visual acuity, preoperative
      visual fields could be obtained; these patients showed significant improvement in
      postoperative perimetry. Five patients had some loss of vision, which made it
      impossible to obtain preoperative visual fields. CONCLUSION: Relaxation of the
      scleral ring of the prelaminar and laminar regions of the optic nerve head
      reduces constriction and may prevent necrosis of salvageable but underperfused
      nerve fibers. Despite improvement of visual acuity in our patients, transvitreal
      optic neurotomy should be considered experimental, requiring a randomized
      clinical trial.

PMID- 14574256
TI  - Infectious and presumed noninfectious endophthalmitis after intravitreal
      triamcinolone acetonide injection.
AB  - PURPOSE: To report potentially distinguishing characteristics between bacterial
      endophthalmitis and presumed noninfectious endophthalmitis associated with
      intravitreal triamcinolone acetonide injection. METHODS: Records of two patients
      with culture-proven bacterial endophthalmitis and six patients with presumed
      noninfectious endophthalmitis from intravitreal triamcinolone acetonide
      injections were analyzed retrospectively. RESULTS: Two eyes in two patients with
      culture-proven bacterial endophthalmitis had decreased vision and hypopyon or
      vitritis, but no pain or conjunctival injection 2 weeks after intravitreal
      triamcinolone acetonide injection. Seven eyes in six patients with presumed
      noninfectious endophthalmitis had blurred vision, hypopyon, and variable pain all
      within 2 days of intravitreal triamcinolone injection. All seven eyes were
      followed up closely and had rapid resolution of hypopyon and symptoms.
      CONCLUSION: Bacterial endophthalmitis after intravitreal triamcinolone acetonide
      injection may present in an atypical, relatively delayed manner with decreased
      vision but no pain or redness. Presumed noninfectious endophthalmitis presents
      within 2 days after the injection, may be accompanied by discomfort, and has a
      hypopyon that may be the triamcinolone material itself or a sterile inflammatory
      reaction. In these eyes, the hypopyon and symptoms quickly resolve without
      treatment.

PMID- 14574258
TI  - The role of streptokinase in induction of posterior vitreous detachment: a
      scanning and transmission electron microscopic study of the retina in rabbits.
AB  - PURPOSE: To evaluate the possibility of inducing a posterior vitreous detachment
      (PVD) by intravitreal injection of streptokinase using electron microscopy and
      electrophysiological study. METHODS: The current study was performed on 30 eyes
      of 15 male white rabbits. The rabbits were divided into three equal groups. The
      right eye of the three groups received an intravitreal injection of streptokinase
      at three different concentrations (150, 1,500 and 15,000 IU in 0.1 mL balanced
      salt solution) in the mid vitreous cavity. The left eye in all animals received
      an intravitreal injection of balanced salt solution and was considered the
      control group. Electroretinography was performed 1 day and 1 week after
      injection. The rabbits were killed after 10 days, and the enucleated eyes were
      processed for transmission and scanning electron microscopic examination.
      RESULTS: In Group 1, scanning electron microscopy showed the retinal surface
      covered with thin collagen fibers, whereas in Group 2, a complete PVD with bare
      retinal surface was seen. Group 3 showed a bare retinal surface with hemorrhagic
      reaction and toxic effects on the retina by transmission electron microscopy.
      CONCLUSION: An intravitreal injection of 1,500 IU of streptokinase can lead to a
      PVD without major toxic effects on the retina.

PMID- 14574259
TI  - Diagnostic and therapeutic challenges.

PMID- 14574260
TI  - External drainage of subretinal fluid using 532-nm green-yellow laser.

PMID- 14574261
TI  - Identification of well-defined intrachoroidal neovascularization by high-speed
      indocyanine green angiography.

PMID- 14574262
TI  - Vitrectomy with indocyanine green-guided inner limiting membrane peeling for a Q
      switched Nd:YAG laser-induced macular hole.

PMID- 14574263
TI  - Posterior scleritis presenting with annular choroidal detachment as a
      complication of herpes zoster ophthalmicus.

PMID- 14574265
TI  - Surgically excised focal posttraumatic choroidal granulomatous inflammation.

PMID- 14574264
TI  - Posterior scleritis in psoriatic arthritis.

PMID- 14574266
TI  - Newly designed self-retaining prism contact lens for vitreous surgery.

PMID- 14574268
TI  - Dislocated ganciclovir implant from use of a nylon fixation suture.

PMID- 14574267
TI  - Prolonged pain following unintentional injection of gas into the suprachoroidal
      space during pneumatic retinopexy.

PMID- 14574269
TI  - Intraretinal hemorrhages and chronic subdural effusions: glutaric aciduria type 1
      can be mistaken for shaken baby syndrome.

PMID- 14574270
TI  - Saccular aneurysms in a case of choroidal melanoma.

PMID- 14574271
TI  - "Comet" lesion: an ocular sign of pseudoxanthoma elasticum.

PMID- 14574272
TI  - A case of X-linked retinoschisis diagnosed in an infant.

PMID- 14574273
TI  - Reduction of the toxic effect of indocyanine green on retinal pigment epithelium
      during macular hole surgery.

PMID- 14574274
TI  - Cutaneous leishmaniasis in U.S. military personnel--Southwest/Central Asia, 2002
      2003.
AB  - Cutaneous leishmaniasis (CL), a vector-borne parasitic disease, is a risk for
      persons, including military personnel, who travel to or live in areas of the
      tropics, subtropics, and southern Europe where the disease is endemic. This
      report provides preliminary data about 22 cases of CL in military personnel
      deployed during 2002-2003 to three countries in Southwest/Central Asia
      (Afghanistan, Iraq, and Kuwait). The patients were evaluated and treated at
      Walter Reed Army Medical Center (WRAMC) in the District of Columbia during August
      2002-September 2003. U.S. health-care providers should consider the possibility
      of CL in persons with chronic skin lesions who were deployed to Southwest/Central
      Asia or who were in other areas where leishmaniasis is endemic.

PMID- 14574275
TI  - Infant health among Puerto Ricans--Puerto Rico and U.S. mainland, 1989-2000.
AB  - Although the overall U.S. infant mortality rate (IMR) declined dramatically
      during the 1900s, striking racial/ethnic disparities in infant mortality remain.
      Infant health disparities associated with maternal place of birth also exist
      within some racial/ethnic populations. Eliminating disparities in infant health
      is crucial to achieving the 2010 national health objective of reducing the infant
      death rate to 4.5 per 1,000 live births (objective 16-1c). Hispanics comprise the
      largest racial/ethnic minority population in the United States. Among U.S.
      Hispanics, considerable heterogeneity exists in infant health, with the poorest
      outcomes reported among Puerto Rican infants. This report compares trends during
      the previous decade in IMRs and major determinants of these rates such as low
      birthweight (LBW), preterm delivery (PTD), and selected maternal characteristics
      among infants born to Puerto Rican women on the U.S. mainland (50 states and the
      District of Columbia) with corresponding trends among infants born in Puerto
      Rico. The findings indicate that despite having lower prevalence of selected
      maternal risk factors, Puerto Rico-born infants are at greater risk for LBW, PTD,
      and infant death than mainland-born Puerto Rican infants. This report also
      highlights a persistent disparity in IMRs and an emerging disparity in LBW and
      PTD rates between Puerto Rico-born infants and mainland-born Puerto Rican
      infants. Future research should focus on identifying factors responsible for
      these disparities to improve infant health in Puerto Rico.

PMID- 14574276
TI  - West Nile virus infection among turkey breeder farm workers--Wisconsin, 2002.
AB  - In 2002, Wisconsin public health officials were notified of two cases of febrile
      illness in workers at a commercial turkey breeder farm (farm A) in county A. The
      Wisconsin Division of Public Health (WDPH) initiated an investigation that found
      a high prevalence of West Nile virus (WNV) antibody among farm A workers and
      turkeys. An associated high incidence of febrile illness among farm A workers
      also was observed. This report summarizes the results of this investigation,
      which indicate possible nonmosquito transmission among birds and subsequent
      infection of humans at farm A. Because the mode of transmission in this outbreak
      is unknown, turkey handlers should take appropriate precautions, including use of
      DEET--containing mosquito repellents, protective clothing and gloves, respiratory
      protection, and proper hand hygiene. Suspected occupationally acquired WNV
      infections should be reported immediately to local and state health departments.

PMID- 14574277
TI  - Public health and aging: nonfatal injuries among older adults treated in hospital
      emergency departments--United States, 2001.
AB  - Because injuries generally are considered a problem of the young, injuries among
      older adults (i.e., persons aged > or =65 years) have received little attention.
      However, injuries are the eighth leading cause of death among older adults in the
      United States. In 2001, approximately 2.7 million older adults were treated for
      nonfatal injuries in hospital emergency departments (EDs); the majority of these
      injuries were the result of falls. To characterize nonfatal injuries among older
      adults, CDC analyzed data from the National Electronic Injury Surveillance System
      All Injury Program (NEISS-AIP). This report summarizes the results of that
      analysis, which indicate differences in type and mechanism of injury by sex,
      suggesting that prevention programs should be designed and tailored differently
      for men and women.

PMID- 14574278
TI  - West Nile virus activity--United States, October 16-22, 2003.
AB  - This report summarizes West Nile virus (WNV) surveillance data reported to CDC
      through ArboNET as of 3 a.m., Mountain Daylight Time, October 22, 2003.

PMID- 14574279
TI  - Guidelines for maintaining and managing the vaccine cold chain.
AB  - In February 2002, the Advisory Committee on Immunization Practices (ACIP) and
      American Academy of Family Physicians (AAFP) released their revised General
      Recommendations on Immunization, which included recommendations on the storage
      and handling of immunobiologics. Because of increased concern over the potential
      for errors with the vaccine cold chain (i.e., maintaining proper vaccine
      temperatures during storage and handling to preserve potency), this notice
      advises vaccine providers of the importance of proper cold chain management
      practices. This report describes proper storage units and storage temperatures,
      outlines appropriate temperature-monitoring practices, and recommends steps for
      evaluating a temperature-monitoring program. The success of efforts against
      vaccine-preventable diseases is attributable in part to proper storage and
      handling of vaccines. Exposure of vaccines to temperatures outside the
      recommended ranges can affect potency adversely, thereby reducing protection from
      vaccine-preventable diseases. Good practices to maintain proper vaccine storage
      and handling can ensure that the full benefit of immunization is realized.

PMID- 14574281
TI  - Arytenoid adduction combined with medialization thyroplasty: an evidence-based
      review.
AB  - OBJECTIVE: Medialization thyroplasty (MT) and arytenoid adduction (AA) are
      effective treatments for medializing the paralyzed vocal cord, but indications
      and benefits of each procedure are controversial. We performed a formal evidence
      based review to answer this question: In patients with unilateral vocal cord
      paralysis, does AA combined with MT significantly improve subjective and
      objective voice outcomes compared with MT alone?Study design We performed a
      MEDLINE literature search using specific search terms to identify pertinent
      articles, which were reviewed and graded according to the evidence quality.
      RESULTS: We identified 219 potentially pertinent articles; detailed review
      yielded 10 studies for further analysis. Only 3 studies directly compared MT with
      AA plus MT: overall, there was no clear benefit in subjective or objective
      outcomes for AA plus MT. CONCLUSIONS: Very limited grade C evidence indicates no
      clear benefit, or lack of benefit, in subjective or objective outcomes if AA is
      added to MT, compared with MT alone.

PMID- 14574280
TI  - Skin testing for inhalant allergy 2003: current strategies.

PMID- 14574284
TI  - Pharyngeal flap surgery: protocols, complications, and outcomes at the University
      of Iowa.
AB  - OBJECTIVE: We sought to assess complication rates and speech outcomes in patients
      undergoing pharyngeal flap surgery. Study design and setting We conducted a
      retrospective chart and database review at a tertiary craniofacial center.
      PATIENTS: Eighty-seven patients were identified as having pharyngeal flaps
      between January 1990 and December 2000. RESULTS: Complications were rare, with an
      overall rate of 3.4% for all children. Craniofacial database records were
      identified with a follow-up examination between 2 and 5 years. Forty-four
      patients were identified. Of this group, 81.8% demonstrated no evidence of
      hypernasality or mild hypernasality, and 84.1% demonstrated no evidence of
      hyponasality or only mild hyponasality. Preoperative and postoperative
      assessments showed a statistically significant difference in hypernasality at P <
      0.001 with no significant difference in hyponasality. CONCLUSIONS: Although
      sphincter pharyngoplasty procedures have gained a great deal of attention in the
      recent otolaryngologic literature, pharyngeal-flap procedures remain a valuable
      tool in the hands of surgeons dealing with velopharyngeal incompetence.

PMID- 14574283
TI  - Voice and deglutition functions after the supracricoid and total laryngectomy
      procedures for advanced stage laryngeal carcinoma.
AB  - OBJECTIVES: This investigation compared speech and deglutition functions after
      alternative surgical treatments for advanced stage laryngeal carcinoma: the
      supracricoid laryngectomy (SCL) versus the total laryngectomy (TL). Study design
      and setting Cohort investigation at Wayne State University School of Medicine.
      METHODS: Quantitative studies of laryngeal biomechanics, acoustic and speech
      aerodynamic features, and deglutition skills of these individuals were coupled to
      listener and patient self-impressions of speech and voice characteristics for
      group comparative analyses. RESULTS: Results revealed that patients from each
      subgroup performed comparably relative to speech intelligibility and voice
      quality disturbances. Videostroboscopy of the neoglottal mechanisms in these two
      populations helped to explain these outcomes. Acoustic and speech aerodynamic
      testing demonstrated variably abnormal features in both surgical subgroups.
      Whereas the SCL patients eventually achieved full oral diets, they required many
      sessions of swallowing therapy to obtain this objective and eliminate tube
      feeding supplementation. The TL patients did not evidence protracted swallowing
      difficulties or the need for specific exercises in order to remove their feeding
      tubes postoperatively. References to organ preservation strategies in lieu of
      surgical management are included for completeness purposes. CONCLUSIONS: The SCL
      and TL surgical procedures for advanced stage laryngeal carcinoma resulted in
      equivalent speech and swallowing functional outcomes.

PMID- 14574285
TI  - The efficacy of anatomically based multilevel surgery for obstructive sleep
      apnea.
AB  - OBJECTIVE: Most reports in the literature focus on the efficacy of a single
      procedure for obstructive sleep apnea (OSA). We review the overall efficacy of a
      surgical methodology based on localizing the level of anatomic obstruction for
      each patient and surgical correction of the nasal, oropharyngeal, or
      hypopharyngeal obstruction. Study design and setting Retrospective review of
      cases performed by a single practitioner using a systematic approach to surgery
      for OSA with preoperative and postoperative sleep studies. RESULTS: Forty-two
      patients with a respiratory disturbance index (RDI) greater than 15 were included
      in the study. Surgery involved at least 2 levels of obstruction usually performed
      in 2 stages. All patients reported symptomatic improvement. Overall, 83.3% (35 of
      42) of patients were cured according to the accepted RDI criteria of more than
      50% reduction and final RDI of less than 20. All 21 patients with mild OSA (RDI,
      <29), 73% of patients with moderate OSA (RDI, 30 to 49), and 50% of patients with
      severe OSA (RDI, >50) were cured. CONCLUSION: The use of an anatomically based
      methodology in approaching patients with OSA seems to offer a higher efficacy
      than a single procedure as reported in the literature.

PMID- 14574286
TI  - Use of 3-dimensional computed tomography scan to evaluate upper airway patency
      for patients undergoing sleep-disordered breathing surgery.
AB  - OBJECTIVE: Our goal was to investigate the correlation between upper airway 3
      dimensional computed tomography (3-D CT) measurements and polysomnography data of
      patients with sleep-disordered breathing (SDB). Study design and setting The 3-D
      CT scan measurements of the retropalatal space (RP), lateral and anteroposterior
      diameters of RP, retroglossal space, uvular thickness, and volume of upper airway
      were taken prospectively from 194 consecutive SDB patients. These were correlated
      with patients' respective Respiratory Distress Index (RDI), snoring index, and
      lowest arterial oxygen saturation gathered from polysomnographic data. RESULTS:
      RP (r = -0.27, P = 0.0001) and lateral diameter (P = 0.0073) were significantly
      correlated with RDI. Multivariate regression model (R(2) = 0.286) demonstrates RP
      (P = 0.0036) and retroglossal space (P = 0.027) to be predictive of RDI. No 3-D
      CT parameters correlated with snoring index and lowest arterial oxygen saturation
      attained statistical significant. CONCLUSION: The 3-D CT scan measurements can be
      valuable in evaluating upper airway patency in patients with SDB. The RP was the
      most relevant upper airway anatomic structure identified in these patients.
      SIGNIFICANCE: Modification of palatal surgery to increase the lateral dimension
      of the RP may be a breakthrough in increasing its success rate.

PMID- 14574287
TI  - Evaluation of palatal snoring surgery in an animal model.
AB  - OBJECTIVE: We introduce an animal model to reproduce and measure palatal snoring
      and to assess the effectiveness of cautery-assisted palatal stiffening operation
      and injection snoreplasty versus a control (no palatal intervention) on treatment
      of palatal flutter snoring. Study design and setting An anesthetized laboratory
      canine model uses 2 simultaneous temporary tracheotomies. An inferior tracheotomy
      is cannulated with an endotracheal tube for ventilation. A superior tracheotomy
      is cannulated with a tube passed cephalad and seated in the hypopharynx. Negative
      pressure applied to the upper tube leads to partial collapse of the upper airway
      with palatal fluttering, and the anesthetized dog snores. Videostroboscopy
      records palatal flutter frequency before and after surgical intervention.
      Preoperative and postoperative palatal assessments are made on 15 beagles.
      RESULTS: Cautery-assisted palatal stiffening operation and injection snoreplasty
      objectively stiffen the canine soft palate with diminished snoring compared with
      controls. Conclusion and significance We provide a reproducible animal model to
      experimentally measure new interventions to treat palatal flutter snoring.

PMID- 14574288
TI  - Uvulopalatal flap for snoring on an outpatient basis.
AB  - OBJECTIVE: Snoring is now seen as one end of a spectrum of sleep-related
      breathing disorders, and in its extreme form, snoring can cause obstructive sleep
      apnea syndrome. Since the introduction of uvulopalatopharyngoplasty, many other
      procedures have been introduced to alleviate palatal abnormalities seen in
      patients with obstructive sleep apnea syndrome. A reversible uvulopalatal flap
      (UPF) achieves the same results as the uvulopalatopharyngoplasty but with less
      postoperative discomfort. The purpose of this study was to assess the safety and
      efficacy of UPF for the treatment of simple snoring on an outpatient basis.
      METHODS: UFP was performed on an outpatient basis under local anesthesia. The
      mucosa on the lingual surface of the uvula and soft palate was removed with cold
      knife dissection. The uvular tip was amputated. The uvula was reflected back
      toward the soft palate and sutured. Most of the patients were male with simple
      snoring by history and confirmed by polysomnographic study. Data on patients were
      compared from preoperative to postoperative assessment points. Statistic analysis
      was performed. RESULTS: Fifty-six patients tolerated the procedure well, and it
      was performed in an average of 20 minutes. Patients had a mean age of 48 years
      and a mean body mass index of 26.5 kg/m(2). The mean follow-up was 14 months
      (range, 12 to 20 months). Significant improvement was observed in snoring scale
      (8.2 +/- 3.4 versus 2.6 +/- 1.4, P < 0.05). Mean snoring index decreased from
      245.8 +/- 40.8 to 42.5 +/- 20.7 events/hr (P < 0.001). The correlations between
      the changes in the subjective and objective snoring assessments were
      statistically significant. Postoperative complications included transient nasal
      regurgitation (4%) and foreign body sensation (2%). Bleeding, dysphagia,
      infection, and nasopharyngeal stenosis were not observed. Most patients had mild
      to moderate pain (visual analog scale, </=7) for 5 to 7 days after the
      procedures. The overall success rate was 88%. CONCLUSION: Snoring, as reported by
      subjective and objective results, decreased after UPF. It appears to be a safe
      and effective procedure, which can be easily performed under local anesthesia on
      an outpatient basis, in carefully selected patients.

PMID- 14574290
TI  - Clinical effectiveness of coblation inferior turbinate reduction.
AB  - OBJECTIVE: We sought to determine the safety and clinical effectiveness of
      coblation (short for "cold ablation") inferior turbinate reduction for turbinate
      hypertrophy. METHODS: A consecutive series of adult patients with inferior
      turbinate hypertrophy were treated with the coblation technique in the office
      setting. Subjective symptoms were assessed prior to treatment and at the 3- and 6
      month intervals after treatment with the Rhinosinusitis Symptom Inventory (RSI)
      and a short nasal symptom questionnaire. RESULTS: Twenty-four of 26 treated
      patients completed the protocol. At the 3-month follow-up, statistically
      significant decreases in the nasal and overall symptom domains of the RSI were
      noted (changes of -10.5 and -8.7, with P = 0.018 and P = 0.015, respectively).
      These improvements were also significant at the 6-month follow-up (-20.1 and 
      15.8 with, P < 0.001 and P < 0.001, respectively). At the 3-month interval, nasal
      obstruction and amount of time with nasal obstruction were significantly
      decreased (P = 0.006 and P = 0.011, respectively). These decreases remained
      statistically significant and slightly larger in magnitude at 6 months (P = 0.001
      and P = 0.006, respectively). Postoperative epistaxis occurred in 2 of 24 (8.3%)
      of patients. CONCLUSION: Coblation inferior turbinate reduction is an effective
      procedure for inferior turbinate hypertrophy. The clinical benefit persists at 6
      months after the procedure.

PMID- 14574289
TI  - Hot versus cold tonsillectomy: a systematic review of the literature.
AB  - OBJECTIVE: We systematically reviewed the literature comparing monopolar
      electrocautery versus cold knife dissection tonsillectomy. METHODS: The MEDLINE
      database was searched using the key words "tonsillectomy," "hot," "cold,"
      "sharp," "bleeding," and "cautery." Selection criteria included prospective
      trials comparing electrodissection versus cold knife dissection on
      posttonsillectomy pain and hemorrhage. Six of the 815 articles met the selection
      criteria. RESULTS: Pooled data for the paired studies showed significantly more
      patients with pain worse on the electrodissection side (148 of 293 = 51%) than
      the cold knife side (33 of 293 [11%]; P = 0.001) on postoperative days 4 to 10.
      There were significantly more analgesic doses after surgery with
      electrodissection (means 26.7 versus 19.2; P = 0.028) and higher pain scores for
      adults undergoing electrodissection (means, 2.6 versus 0.8; significance could
      not be determined). There were no differences in hemorrhage rates. CONCLUSIONS:
      Electrodissection increases pain in comparison to sharp dissection for
      tonsillectomy. Postoperative hemorrhage rates are not significantly different
      when comparing the 2 methods.

PMID- 14574291
TI  - Classification of fungal sinusitis in immunocompetent patients.
AB  - OBJECTIVE: The objective of this study was to review the subgroup classification
      of fungal sinusitis in immunocompetent patients. METHODS: The study design
      included 19 immunocompetent patients with fungal sinusitis who were operated on
      between 1993 and 1998. RESULTS: Ten of 19 patients showed a fungus ball. They
      underwent a limited surgical endoscopic procedure, and no further treatment was
      needed. Four patients had allergic fungal sinusitis and were treated
      postoperatively with irrigation, topical steroids, and oral steroids in 2
      patients as well. Five patients had chronic sinusitis with significant bone
      erosion. All 5 underwent an extensive endoscopic procedure and were treated
      postoperatively by repeated irrigation, endoscopic cleaning, and no antifungal
      preparation. Two patients of this group are reported broadly. CONCLUSIONS: Fungal
      sinusitis in immunocompetent patients is not a rare condition and can be divided
      into 3 categories: 1) fungus ball, 2) chronic erosive (noninvasive) fungal
      sinusitis, and 3) allergic fungal sinusitis. The symptomatology, treatment, and
      prognosis varied significantly among the 3 different categories.

PMID- 14574292
TI  - Acyclovir in the treatment of Ramsay Hunt syndrome.
AB  - Ramsay Hunt syndrome is an herpetic disease with ominous prognosis regarding the
      facial nerve. Treatment with acyclovir, a well-known virostatic agent, has been
      given in a small number of patients in recent years with excellent results. We
      report on the administration of acyclovir intravenously for 7 days in 31 patients
      with Ramsay Hunt syndrome, with overall recovery rate of 82.6%. There were no
      side effects regarding this treatment.

PMID- 14574293
TI  - The effects of aging and hearing loss on distortion product otoacoustic
      emissions.
AB  - OBJECTIVE: We sought to demonstrate the rate of change in distortion product
      otoacoustic emission (DPOE) amplitude with age in relation to hearing loss in an
      unselected adult population. Study design and setting We conducted a cross
      sectional observation study involving the Framingham Offspring Cohort. Age
      changes in DPOE amplitude for frequencies of f2 from 1 to 8 kHz adjusted for pure
      tone threshold level were assessed by multivariate linear regression. RESULTS:
      The women showed a mean hearing threshold-adjusted loss in high-frequency DPOE
      amplitude of 0.6, 2.1, 2.6, and 1.1 dB/per decade at the f2 frequencies of 1, 2,
      4, and 8 kHz, respectively. In contrast, the men showed no effect of age on the
      DPOE amplitude independent of hearing loss. Emissions were reduced or absent in
      the noise notch frequencies. The rate of change with age in DPOE amplitude was
      significantly less than the rate of change in pure-tone thresholds in both the
      men and the women. CONCLUSION: Women lose DPOE amplitude from both age and
      hearing threshold loss. Men lose more DPOE amplitude than do women, and the loss
      is proportional to the degree of loss of hearing threshold sensitivity. The
      differential effect whereby age-related hearing loss affects thresholds more than
      emissions suggests that strial atrophy may be a pathophysiologic factor.
      SIGNIFICANCE: The use of DPOE measures for screening and monitoring cochlear
      status of adult women should take into account the age, pure-tone thresholds, and
      noise exposure status of the subjects.

PMID- 14574294
TI  - Normal features of tissue-engineered auricular cartilage by flow cytometry and
      histology: patient safety.
AB  - BACKGROUND: Cytokinetic abnormalities in DNA content, such as aneuploidy,
      haploidy, and tetraploidy, have been found to occur in human cartilaginous
      tumors. The high number of chondrocytes needed for tissue-engineered
      cartilaginous implants requires the cells to be passaged repeatedly. The
      theoretical risk of changes in the normal diploid state of these cells during
      their growth in vitro and after generation of tissue-engineered cartilage in vivo
      is not known. Materials and methods Auricular chondrocytes were obtained from 6
      patients and cultured in vitro. Chondrocyte number was increased by repeated
      passaging. The passaged cells were implanted in nude mice for 8 weeks to generate
      tissue-engineered cartilage. Fresh control chondrocytes along with the passaged
      cells and cells obtained from the tissue-engineered constructs were collected and
      compared for DNA content by flow cytometry. RESULTS: Flow cytometry demonstrated
      100% diploidy with no evidence of aneuploidy, haploidy, or tetraploidy in all
      groups of cells. Histology of the tissue-engineered cartilage also showed no
      evidence of cellular atypia. CONCLUSION: The number of human auricular
      chondrocytes can be increased by repeated passaging and passaged chondrocytes can
      be safely used for implantation to generate tissue-engineered constructs without
      a change in the normal diploid state of the cells. Histology of the cartilage
      generated showed normal features without atypia.

PMID- 14574295
TI  - Hearing preservation with the retrosigmoid approach for vestibular schwannoma:
      myth or reality?
AB  - OBJECTIVE: The purpose of this study is to present our experience with the
      retrosigmoid approach for vestibular schwannoma resection, emphasizing our
      hearing results, discussing selection and reporting results criteria.Study design
      and setting The notes of 65 consecutive cases of vestibular schwannoma undergoing
      the retrosigmoid approach were reviewed. Hearing data were reported according to
      the recommendations of the American Academy of Otolaryngology-Head and Neck
      Surgery (AAO-HNS). In addition, the terms normal, serviceable, useful, and
      measurable hearing were considered. RESULTS: Tumor size ranged from 8 to 50 mm
      (mean, 24.1 mm). Of the 29 patients with preoperative serviceable hearing (AAO
      HNS classes A and B), 5 patients (17%) had postoperative serviceable hearing, and
      6 patients (20%) had postoperative useful hearing (AAO-HNS classes A, B, and C).
      CONCLUSION: The retrosigmoid approach is a reliable surgical procedure for most
      vestibular schwannoma tumors. However, hearing preservation results show wide
      differences depending on selection and reporting results criteria. Hearing
      preservation, although possible, may not be the main reason to choose this
      approach.

PMID- 14574296
TI  - Matrix metalloproteinases in a gerbil cholesteatoma model.
AB  - OBJECTIVE: The goal of this study was to determine whether expression of matrix
      metalloproteinases (MMP) and tumor necrosis factor-alpha (TNF-alpha) occurs in a
      gerbil cholesteatoma model, which may be involved early in the pathogenesis of
      cholesteatoma. Study design Atelectasis was induced by transpalatal, bilateral
      Eustachian tube obstruction on gerbil ears (n = 60). Tympanic membranes were
      removed at days 0, 3, 7, 14, 28, 56, and 84, and quantitative analysis of TNF
      alpha and MMPs was performed. RESULTS: Atelectasis and middle ear inflammation
      increased with time. TNF-alpha and MMP levels increased (P < 0.0083) with time,
      inflammation, and atelectatic stage with some variability seen between different
      MMPs. CONCLUSION: Elevation of TNF-alpha and MMPs associated with progressive
      tympanic membrane atelectasis suggests a possible role for these inflammatory
      mediators in the pathogenesis of cholesteatoma.

PMID- 14574297
TI  - Transtympanic iontophoresis of gadopentetate dimeglumine: Preliminary results.
AB  - OBJECTIVE: We sought to demonstrate the feasibility of using iontophoresis to
      deliver pharmaceutical agents into the middle and inner ear for the treatment of
      middle and inner ear diseases, which is proved in this study by the successful
      iontophoresis of the ferromagnetic contrast agent gadopentetate dimeglumine.
      Study design and setting Eight rabbits were iontophoresed using gadopentetate
      dimeglumine solution 469 mg/mL. Then, all rabbits underwent magnetic resonance
      imaging for the detection of gadopentetate dimeglumine in the middle and inner
      ear structures. The study was conducted in the tertiary referral center the
      University Hospital of Crete. RESULTS: The high signal intensity of the
      gadopentetate dimeglumine solution was demonstrated within the middle ear cavity
      and inner ear structures of all iontophoresed ears and in none of the
      noniontophoresed ones. CONCLUSIONS: Transtympanic iontophoresis could be an
      effective method for the passage of pharmaceutical agents into the middle and
      inner ear for the treatment of middle and inner ear diseases.

PMID- 14574298
TI  - The wound amylase concentration in the prediction of pharyngocutaneous fistula.
AB  - Pharyngocutaneous fistula (PCF) is not uncommon after laryngeal surgery. Because
      it leads to prolonged hospitalization and increased patient morbidity, it is
      important to predict the formation of fistula. We studied the wound amylase
      concentrations of 87 consecutive laryngectomized patients. The PCF rate was 11.5%
      in this series. The amylase levels in patients with PCF begin to elevate
      significantly on the third, fourth, and fifth postoperative days. Our data
      indicate that increase in the wound amylase levels seems to be a significant
      predictor of PCF, and this should alert the surgeon for the presence of fistula.

PMID- 14574299
TI  - Mandibular reconstruction with an alloplastic bone tray in dogs.
AB  - OBJECTIVE: Mandibular alloplastic bone trays have an unacceptably high rate of
      extrusion. The introduction of resorbable mesh has renewed interest in such
      trays. This study evaluates the effect of resorbable trays on bone graft healing
      in a dog model. DESIGN: Unilateral, 20-mm mandibular body defects were created in
      10 dogs, and repaired with cancellous bone grafts. A resorbable mesh bone tray
      was applied to 5 animals. All mandibles underwent gross examination, 4-point
      stress testing, and histologic and radiographic analysis. RESULTS: All animals
      had excellent bony unions. There was one intraoral mesh exposure. There was no
      difference between the control and treatment groups with regard to clinical
      findings, radiologic analysis, stress testing (P = 0.17), or histologic analysis
      (P = 0.66). CONCLUSION: The metabolic breakdown products of the resorbable mesh
      do not inhibit bone healing or strength. Resorbable mesh trays are a viable
      modality for reconstruction of segmental mandibular defects in a dog model.

PMID- 14574300
TI  - Endoscopic modified Lothrop procedure for the treatment of chronic frontal
      sinusitis: a systematic review.
AB  - OBJECTIVE: We sought to assess the safety and efficacy of the endoscopic modified
      Lothrop procedure (EMLP), performed either wholly intranasally or in combination
      with an external approach, against the osteoplastic flap (OPF) procedure with or
      without fat obliteration. METHODS: All original, published studies on the EMLP
      and the OPF, with or without fat obliteration, were identified by searching
      Current Contents, Embase, MEDLINE, and The Cochrane Library. The search strategy
      for OPF was date-restricted to articles published after 1979 until February 2001.
      For both EMLP and OPF, only studies of patients diagnosed with chronic frontal
      sinusitis were included for review. English-language reports detailing randomized
      controlled trials, controlled clinical trials, case series, or case reports were
      included. RESULTS: The limited comparative data suggested that EMLP caused fewer
      adverse postoperative outcomes but was more likely to generate a perioperative
      cerebrospinal fluid leak than OPF. However, none of the morbidity traditionally
      associated with OPF was evident after EMLP. EMLP appeared to have a shorter
      operative time and a lower perioperative blood loss than OPF, but little could be
      determined regarding the long-term efficacy and durability of EMLP because of the
      relatively short follow-up of the majority of the studies. CONCLUSION: The
      evidence base for EMLP was deemed inadequate to assess its safety and efficacy,
      and an audit of the procedure was recommended. Additional clinical
      recommendations were made regarding the development and current practice of EMLP
      during this audit phase.

PMID- 14574301
TI  - Intralabyrinthine schwannoma: subtle differentiating symptomatology.

PMID- 14574302
TI  - Pulse granuloma in the wall of an inflammatory radicular cyst.

PMID- 14574303
TI  - Histologic confirmation of carotidynia.

PMID- 14574304
TI  - Abscess of the neck caused by Salmonella enteritidis.

PMID- 14574305
TI  - Posterior ischemic optic neuropathy following endoscopic sinus surgery.

PMID- 14574306
TI  - Parotid gland involvement as an initial presentation of Wegener's granulomatosis.

PMID- 14574307
TI  - Malignant fibrous histiocytoma arising from paraglandular tissue of the parotid
      gland.

PMID- 14574308
TI  - Dumbbell-type intracranial meningioma presenting as an aural polyp and a neck
      mass.

PMID- 14574309
TI  - Actinomycotic thyroid abscess.

PMID- 14574310
TI  - A natural old age.

PMID- 14574317
TI  - Hematology of malnutrition, part one.

PMID- 14574325
TI  - Reactivation of porphyria cutanea tarda as a possible side effect of Imatinib at
      high dosage in chronic myeloid leukemia.

PMID- 14574326
TI  - Constitutive NF-kappaB DNA-binding activity in AML is frequently mediated by a
      Ras/PI3-K/PKB-dependent pathway.
AB  - In the present study, we aimed to elucidate the mechanism responsible for
      constitutive NF-kappaB DNA-binding activity in AML cells. Intervening in aberrant
      signaling pathway provides a rational approach for in vivo targeting of AML
      cells. Constitutive NF-kappaB DNA-binding activity was observed in 16 of 22 (73%)
      investigated AML cases and was, in general, associated with resistance to
      spontaneous apoptosis. Indeed, inhibition of NF-kappaB activity by the NF-kappaB
      inhibitor SN-50 peptide resulted in enhanced chemotherapy-induced apoptosis. In
      the majority of cases, constitutive NF-kappaB activity was mediated by a Ras/PI3
      kinase (PI3-K)/protein kinase B (PKB)-mediated pathway. The PI3-K inhibitor
      Ly294002 and the Ras inhibitor L-744832 both inhibited PKB phosphorylation and NF
      kappaB DNA-binding activity. The constitutive activation of Ras GTP-ase was
      caused by mutations in the gene encoding for N-Ras in 29% of the cases. The
      constitutive NF-kappaB activity could so far not be ascribed to the autocrine
      production of growth factors or to mutations in the Flt3 receptor, since anti-GM
      CSF, -IL-1, -IL6, -TNFalpha or the tyrosine kinase inhibitor AG1296 did not
      affect the NF-kappaB DNA-binding activity. The present study demonstrates that
      Ras activation is an important pathway for triggering the NF-kappaB pathway in
      AML cells.

PMID- 14574327
TI  - Multidrug resistance genes in infant acute lymphoblastic leukemia: Ara-C is not a
      substrate for the breast cancer resistance protein.
AB  - Infants with acute lymphoblastic leukemia (ALL) are more resistant to
      chemotherapeutic drugs than older children with ALL, except for Ara-C. Drug
      resistance mechanisms in infant ALL, however, remain unknown. Possibly, multidrug
      resistance (MDR) proteins like P-glycoprotein, MDR-associated protein (MRP1),
      lung resistance-related protein (LRP/MVP) and the breast cancer resistance
      protein (BCRP) play a role. Accordingly, we measured the mRNA levels of these
      proteins in infants (n=13) and non-infants (n=13) with ALL, using quantitative RT
      PCR. Infants expressed 2.4-fold less BCRP mRNA (P=0.009) than non-infants with
      ALL. MDR1, MRP1 and LRP/MVP expression did not differ between both groups. MDR
      gene expression levels did not correlate to prednisolone, vincristine,
      daunorubicin or Ara-C cytotoxicity, except for BCRP expression, which correlated
      with resistance to Ara-C (Rs=0.53, P=0.012), suggesting that Ara-C might be a
      BCRP substrate. However, culturing patients ALL cells in the presence of the BCRP
      inhibitor Ko143 had no effect on Ara-C sensitivity. Inhibiting Bcrp1 in the Mdr1a
      , Mdr1b- and Mrp1-deficient and Bcrp1-overexpressing mouse cell line
      Mef3.8/T6400, also did not modulate Ara-C cytotoxicity. Therefore, we conclude
      that Ara-C is not a substrate for BCRP and that MDR proteins do not play a
      significant role in drug resistance in infant ALL.

PMID- 14574328
TI  - Post-transcriptional regulation of inducible nitric oxide synthase in chronic
      lymphocytic leukemia B cells in pro- and antiapoptotic culture conditions.
AB  - Functional inducible NOS (iNOS) may be involved in the prolonged lifespan of
      chronic lymphocytic leukemia cells (B-CLL), although the exact mechanisms
      implicated remain elusive as yet. In this work, we have examined iNOS expression
      in normal B lymphocytes and B-CLL cells in pro- and antiapoptotic conditions. Our
      results demonstrate: (1) The existence of a new splice variant characterized by a
      complete deletion of exon 14 (iNOS 13-16(14del)), which was preferentially
      detected in normal B lymphocytes and may represent an isoform that could play a
      role in the regulation of enzyme activity. (2) The existence of another
      alternatively spliced iNOS mRNA transcript involving a partial deletion of the
      flavodoxin region (iNOS 13-16(neg)) was correlated to a decreased B-CLL cell
      viability. The 9-beta-D-arabinofuranosyl-2-fluoradenine or fludarabine (F-ara)
      treatment induced iNOS 13-16(neg) transcript variants, whereas IL-4 enhanced both
      the transcription of variants, including these exons (iNOS 13-16(pos)), and the
      expression of a 122 kDa iNOS protein. These results suggest that in B-CLL, a
      regulation process involving nitric oxide (.- NO) levels could occur by a post
      transcriptional mechanism mediated by soluble factors. Our results also provide
      an insight into a new complementary proapoptotic action of F-ara in B-CLL by the
      induction of particular iNOS splice variants, leading to the activation of a
      caspase-3-dependent apoptotic pathway.

PMID- 14574329
TI  - NF-kappaB/Rel-mediated regulation of apoptosis in hematologic malignancies and
      normal hematopoietic progenitors.
AB  - The activity of NF-kappaB/Rel transcription factors can downmodulate apoptosis in
      normal and neoplastic cells of the hematologic and other compartments,
      contributing in maintaining neoplastic clone survival and impairing response to
      therapy. Alterations in nfkappab or ikappaB genes are documented in some
      hematologic neoplasias, while in others dysfunction in NF-kappaB/Rel-activating
      signaling pathways can be recognized. The prosurvival properties of NF-kappaB/Rel
      appear to rely on the induced expression of molecules (caspase inhibitors, Bcl2
      protein family members, etc.), which interfere with the apoptosis pathway.
      Constitutive NF-kappaB/Rel activity in some hematologic malignancies could be
      advantageous for neoplastic clone expansion by counteracting stress stimuli
      (consumption of growth factors and metabolites) and immune system-triggered
      apoptosis; it is furthermore likely to play a central role in determining
      resistance to therapy. Based on this evidence, NF-kappaB/Rel-blocking approaches
      have been introduced in antineoplastic strategies. The identification of NF
      kappaB/Rel target genes relevant for survival in specific neoplasias is required
      in order to address tailored therapies and avoid possible detrimental effects due
      to widespread NF-kappaB/Rel inhibition. Moreover, comparative analyses of normal
      hematopoietic progenitors and neoplastic cell sensitivities to inhibitors of NF
      kappaB/Rel and their target genes will allow to evaluate the impact of these
      tools on normal bone marrow.

PMID- 14574330
TI  - Homing and mobilization of hematopoietic stem cells and hematopoietic cancer
      cells are mirror image processes, utilizing similar signaling pathways and
      occurring concurrently: circulating cancer cells constitute an ideal target for
      concurrent treatment with chemotherapy and antilineage-specific antibodies.
AB  - Adhesion molecules and stromal cell-derived factor-1 (SDF-1)/CXCR4 signaling play
      key role in homing and mobilization of hematopoietic progenitor (HPC) and
      hematopoietic cancer clonogenic cells (HCC). High expression of VLA-4 is required
      for homing of HPC and HCC, whereas downregulation of these molecules is required
      for successful mobilization of HPC and HCC. Upregulation and activation of the
      SDF-1/CXCR4 signaling is required for homing of HPC and HCC, whereas disruption
      of the SDF-1 signaling is required for mobilization of HPC and HCC. Hence,
      mobilizations of HPC and HCC occur concurrently. It is proposed that drug
      resistance evolves as a result of repeated cycles of chemotherapy. Following each
      cycle of chemotherapy, HCC lose adhesion molecules and SDF-1 signaling. Surviving
      cells, released from tumor sites, circulate until re-expression of adhesion
      molecules and CXCR4 occurs, then homing to stroma of distal tissues occurs.
      Cytokines secreted by cells in the new microenvironment induce proliferation and
      drug resistance of HCC. This process is amplified in each cycle of chemotherapy
      resulting in disease progression. A novel model for treatment is proposed in
      which circulating HCC are the target for clinical intervention, and concurrent
      treatment with chemotherapy and antilineage-specific antibodies will result in
      abrogation of the 'vicious cycle' of conventional anticancer therapy.

PMID- 14574331
TI  - Loss of the ex vivo but not the reinducible CD8+ T-cell response to Tax in human
      T-cell leukemia virus type 1-infected patients with adult T-cell
      leukemia/lymphoma.
AB  - Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia/lymphoma
      (ATLL) and HTLV-1-associated myelopathy (HAM). In asymptomatic carriers and HAM
      patients, HTLV-1 infection leads to a vigorous cytotoxic T-cell (CTL) response
      mainly directed to the regulatory Tax protein. In contrast, initial studies
      showed that anti-HTLV-1 CTL activities were not reproductively detected in ATLL
      patients, neither ex vivo, nor after in vitro restimulation. To better understand
      this discrepancy, we explored the anti-HTLV-1 CD8+ T-cell response of eight ATLL
      patients by using in vitro restimulated or freshly isolated CD8+ T cells. In all
      the ATLL patients, we found that mitogenic activation allowed the induction of
      CD8+ T cells able to lyse autologous HTLV-1-infected cells and/or to produce
      IFNgamma in response to Tax peptides. In contrast, only a minority of the
      patients possessed CD8+ cells able to respond ex vivo to the same epitopes. These
      findings indicate that although a restimulatable anti-HTLV-1 CTL activity
      persists during ATLL, the specific ex vivo response is not constantly maintained.
      This provides definitive evidence that the CD8+ T-cell response to HTLV-1 is
      affected by ATLL development and reveals that a major defect concerns the
      generation and/or the functionality of CD8+ effectors.

PMID- 14574332
TI  - Long-term follow-up of idiotype vaccination in human myeloma as a maintenance
      therapy after high-dose chemotherapy.
AB  - The aim of this work was to evaluate the long-term immunological and clinical
      impact of idiotype (Id) vaccination in multiple myeloma (MM) patients in first
      remission after high-dose chemotherapy. A total of 15 patients received a series
      of subcutaneous (s.c.) injections of autologous Id, conjugated to keyhole limpet
      hemocyanin (KLH) and in association with low doses of GM-CSF. The median duration
      of follow-up was 110 months from diagnosis. The vaccine induced immune responses
      that lasted almost 2 years after the end of treatment. Antibody responses
      included anti-KLH IgM and IgG (90% of patients), anti-KLH IgE (30%), anti-GM-CSF
      IgG (20%), anti-Id IgG (20%), and anti-Id IgE (30%). Id-specific delayed type
      hypersensitivity skin tests were positive in 85% of tested patients. Following
      vaccination, a progressive recovery of T-cell receptor (TCR) diversity was
      observed and the loss of oligoclonality was significantly correlated with the
      remission duration. Although Id/KLH conjugates did not eliminate the residual
      tumor burden, the median progression-free survival, and overall survival were 40
      and 82 months, respectively. A retrospective case-matched analysis showed similar
      results in patients treated with IFN-alpha alone or in association with steroids.
      This vaccine formulation can overcome Id-specific immune tolerance by inducing
      clinical responses that are worthy of further investigation.

PMID- 14574334
TI  - Expression and transcriptional regulation of functionally distinct Bmf isoforms
      in B-chronic lymphocytic leukemia cells.
AB  - Bmf is a BH3-only Bcl-2 family member that is normally sequestered to myosin V
      motors by binding to the dynein light chain 2 (DLC2). Certain damage signals
      release Bmf, which then binds prosurvival Bcl-2 proteins and triggers apoptosis.
      Here, two novel isoforms of human Bmf, Bmf-II and Bmf-III, were identified and
      cloned from cDNA derived from B-chronic lymphocytic leukemia (B-CLL) cells. Bmf
      II and Bmf-III were characterized as two splice variants, lacking the BH3 domain
      but retaining the DLC2 binding domain. Bmf (here called Bmf-I) expression in HeLa
      cells induced apoptosis and reduced colony formation in contrast to Bmf-II and
      Bmf-III, which had no effect on apoptosis and instead increased colony formation.
      While bmf-I mRNA was expressed in many cell types, expression was higher in B
      lymphoid cells and bmf-II and bmf-III were mainly detected in B-CLL and normal B
      cells. bmf-I mRNA was upregulated in normal and leukemic B cells, while bmf-III
      mRNA was downregulated only in B-CLL cells by serum deprivation. We show that Bmf
      is regulated by transcriptional activation and alternative splicing and conclude
      that the relative levels of Bmf isoforms may have a role in regulating growth and
      survival in B cells and leukemic B-CLL cells.

PMID- 14574333
TI  - High incidence and unique features of antigen receptor gene rearrangements in TEL
      AML1-positive leukemias.
AB  - The t(12;21) translocation resulting in the TEL-AML1 gene fusion is found in 25%
      of childhood B-cell precursor (BCP) acute lymphoblastic leukemias (ALL). Since
      TEL-AML1 has been reported to induce cell cycle retardation and thus may
      influence somatic recombination, we analyzed 214 TEL-AML1-positive ALL by PCR for
      rearrangements of the immunoglobulin (Ig) and T-cell receptor (TCR) genes. As a
      control group, 174 childhood BCP ALL without a TEL-AML1 were used. The majority
      of TEL-AML1-positive leukemias had a higher number of Ig/TCR rearrangements than
      control ALL. They also had a more mature immunogenotype characterized by their
      high frequency of complete IGH, IGK-Kde, and TCRG rearrangements. While IGK-Kde
      and TCRG were more frequently rearranged on both alleles at higher age, IGH and
      TCRD rearrangements decreased in their incidence along with a decrease in
      biallelic IGH rearrangements. This suggests that the recombination process
      continues in these leukemias leading to ongoing rearrangements and possibly also
      deletions of antigen receptor genes. We here provide first evidence that somatic
      recombination of antigen receptor genes is affected by the TEL-AML1 fusion, and
      that further age-related differences are probably caused by the longer latency
      period of the prenatally initiated TEL-AML1-positive leukemias in older children.

PMID- 14574335
TI  - Primary pulmonary MALT lymphomas show frequent and heterogeneous cytogenetic
      abnormalities, including aneuploidy and translocations involving API2 and MALT1
      and IGH and MALT1.
AB  - API2-MALT1 fusion and aneuploidy are common chromosomal abnormalities in MALT
      lymphoma. In studying their incidence and relationship in primary pulmonary MALT
      lymphomas, a translocation involving MALT1 and IGH was also identified. In all,
      28 primary pulmonary MALT lymphomas were studied by fluorescence in situ
      hybridization using an API2-MALT1 probe and multiple centromeric probes, as well
      as IGH-BCL2, IGH-MALT1, and MALT1 breakapart probes in selected cases. Seven
      (25%) had API2-MALT1 fusion; all seven lacked aneuploidy except for two with
      trisomy 3 in a small clone. Three (11%) had IGH-MALT1 fusion; two also showed
      trisomy 3 and 12. A total of 11 (39%) had aneuploidy only, with trisomy 3 and 18
      being the most common. Ectopic nuclear bcl-10 expression, which has been
      previously associated with API2-MALT1, was seen by immunohistochemistry in 86% of
      API2-MALT1 fusion-positive cases, one IGH-MALT1 fusion-positive case, two
      aneuploidy-only cases, and two normal cases. In primary pulmonary MALT lymphomas,
      cytogenetic abnormalities are common (75%) and heterogeneous, encompassing API2
      MALT1 and IGH-MALT1, which are mutually exclusive, as well as aneuploidy, which
      may be present in the latter but is rare in the former. Ectopic nuclear bcl-10
      expression is associated with API2-MALT1 but may also be seen in IGH-MALT1 fusion
      positive, aneuploidy-only, and normal cases.

PMID- 14574337
TI  - Revisions of cutoffs of body mass index to define overweight and obesity are
      needed for the Asian-ethnic groups.

PMID- 14574338
TI  - Ethnic-specific revisions of body mass index cutoffs to define overweight and
      obesity in Asians are not warranted.
AB  - Studies showing that Asians with a body mass index (BMI) at the high end of the
      'normal' range are at increased risk of disease do not justify a different
      definition of obesity for that ethnic group without comparable data from
      Caucasians showing no similar increase in risk. The current BMI cutpoints for
      obesity are somewhat arbitrary, but there is value in a simple, uniform
      definition across populations. It seems prudent to separate the scientific
      construct of obesity from the politically linked, nationally specific BMI
      cutpoint used to trigger public health or clinical action.

PMID- 14574339
TI  - Does obesity surgery improve psychosocial functioning? A systematic review.
AB  - OBJECTIVE: The objective of this study is to present a review of the psychosocial
      outcome of bariatric surgery with special consideration of psychiatric
      comorbidity, psychopathology, psychosocial functioning, econometric data, and
      general quality of life (QoL). PURPOSE: A review of all (non-) controlled trials
      of the last two decades both with a retrospective and prospective design and a
      follow-up period of at least 1 y. RESEARCH METHODS AND PROCEDURES: The relevant
      literature was identified by a search of computerized databases. All articles
      published in English and German since 1980 were reviewed. Based on the
      requirements of the evidenced-based guidelines of the Agency for Health Care
      Policy and Research and the Scottish Intercollegiate Guidelines Network, each
      study was rated by a level of evidence. RESULTS: In all, 171 publications were
      reviewed. Using the above inclusion/exclusion criteria, 63 articles including two
      systematic reviews were identified. A total of 40 studies focused on psychosocial
      outcome after obesity surgery. CONCLUSION: Mental health and psychosocial status
      including social relations and employment opportunities improve for the majority
      of people after bariatric surgery thus leading to an improved QoL. Psychiatric
      comorbidity, predominantly affective disorders, and psychopathologic symptoms
      decrease postsurgically. A substantial percentage of bariatric surgery patients
      suffer from binge eating disorder or binge eating symptoms. The effect of
      bariatric surgery on the outcome of binge eating symptoms largely depends on the
      type of operation. With the exception of patients with a severe psychiatric
      comorbidity, the concern that obesity surgery will reinforce psychic symptoms and
      lead to a reduction in the QoL seems to be unfounded.

PMID- 14574340
TI  - Influence of adiposity on tonic sympathetic support of resting metabolism in
      healthy adults.
AB  - BACKGROUND: beta-Adrenergic receptor sympathetic nervous system (beta-AR SNS)
      support of resting metabolic rate (RMR) is attenuated with older age, female sex,
      and a sedentary lifestyle. Total and abdominal adiposity and/or body fat pattern
      modulate some SNS-mediated physiological functions. OBJECTIVE: To determine if
      total and abdominal adiposity and/or body fat distribution are independently
      related to SNS support of RMR. DESIGN: Cross-sectional comparison of beta-AR SNS
      support of RMR. SUBJECTS: A total of 54 healthy male and female subjects aged 18
      75 y. MEASUREMENTS: RMR (ventilated hood, indirect calorimetry) before (baseline)
      and during complete beta-AR blockade; body composition by dual energy X-ray
      absorptiometry. RESULTS: Forward stepwise multiple regression analysis using sex,
      exercise status, age group, %body fat, total adiposity, abdominal adiposity, and
      the ratio of abdominal adiposity to hip adiposity as variables revealed sex to be
      the strongest predictor, explaining 21% of the variability in beta-AR SNS support
      of RMR (P=0.0006). Age group explained an additional 4% and exercise status a
      further 4% (both P=0.10). %Body fat, total adiposity, abdominal adiposity, and
      the ratio of abdominal adiposity to hip adiposity did not enter the equation.
      CONCLUSION: Total and abdominal adiposity and body fat pattern are not
      independent physiological determinants of beta-AR SNS support of RMR among
      healthy men and women. Moreover, further support is provided for our previous
      finding of attenuated beta-AR SNS support of RMR with age, female sex, and
      sedentary lifestyle.

PMID- 14574341
TI  - Energy metabolism in Bardet-Biedl syndrome.
AB  - INTRODUCTION: Obesity is a consistent presenting feature of the Bardet-Biedl
      syndrome (BBS), a hereditary disorder caused by a single gene defect. This
      contrasts sharply with general obesity which, despite a strong hereditary
      component, has a multifactorial aetiology. For BBS, the phenotypic
      characterisation of the components of energy balance and the implications for
      their management remains relatively uninvestigated. OBJECTIVE: A case-control
      study to determine whether energy metabolism in subjects with BBS differs from
      matched obese controls and to inform the clinical management of these patients.
      METHODS: A total of 20 overweight and obese subjects with BBS (11 females, 9
      males) matched for age, gender and BMI to 20 subjects without BBS. Resting
      metabolic rate (RMR) was measured by indirect calorimetry, physical activity by
      CSA accelerometry, body composition by the deuterium dilution technique and
      dietary intake by 7-day food records. RESULTS: There was no significant
      difference between BBS and control subjects in body fat (male: % fat=38, s.d. 2.8
      vs 34, s.d. 9.1, female: % fat=45, s.d. 5.9 vs 44, s.d. 8.1; P=0.46] or absolute
      RMR (male: 6.95, s.d. 1.55 MJ/day vs 7.19, s.d. 1.28 MJ/day; P=0.6). After
      adjustment for gender, age, fat-free mass and fat mass, there was no significant
      difference in RMR between BBS and control subjects (F(1, 30)=0.91; P=0.35). A
      lower level of physical activity was observed in BBS subjects (median cnts/min
      259, IQR=153) compared to controls (median cnts/min=306, IQR=119, P=0.02).
      Reported energy intake, macronutrient composition and magnitude of under
      reporting were comparable in both groups. CONCLUSION: This study reveals no
      evidence for systematic differences in energy metabolism in subjects with BBS
      relative to other obese individuals, suggesting that the genetic basis of BBS is
      not associated with specific abnormalities in energy metabolism. This is an
      important finding for clinical management and supports the use of energy
      prescriptions based on RMR for the general obese population plus an appropriate
      allowance for energy expended via physical activity. Further research is needed
      on physical activity in BBS.

PMID- 14574342
TI  - Serum bFGF levels are reduced in Japanese overweight men and restored by a 6
      month exercise education.
AB  - OBJECTIVE: To investigate whether the changes in vascular endothelial growth
      factor (VEGF) and basic fibroblast growth factor (bFGF) concentrations before and
      after weight reduction in Japanese overweight men are associated with changes in
      body mass index (BMI), visceral, subcutaneous fat, VO(2) and work rate (WR) at
      ventilatory threshold (VT). DESIGN: Cross-sectional and longitudinal clinical
      intervention study with exercise education. SUBJECTS: In total, 30 Japanese
      overweight men (BMI, 29.0+/-2.2 kg/m(2)) and 31 normal-weight men (BMI, 22.5+/
      1.6 kg/m(2)) at baseline were enrolled: 30 overweight men (BMI, 29.0+/-2.2
      kg/m(2)) were further enrolled into a 6-month exercise program. MEASUREMENTS: Fat
      distribution evaluated by visceral fat (V) and subcutaneous fat (S) areas
      measured with computed tomography scanning at umbilical levels, angiogenic
      peptides including VEGF and bFGF, exercise tests at baseline and after 6 months.
      RESULTS: In normal-weight and overweight subjects at baseline, VEGF positively
      correlated with S area (r=0.350, P=0.007) but not with V area. In contrast, bFGF
      negatively correlated with BMI (r=-0.619, P<0.001), S (r=-0.457, P<0.001) and V
      areas (r=-0.466, P<0.001). By intervention with exercise education, 30 overweight
      subjects showed reduction in BMI (29.0+/-2.2 to 28.0+/-2.0, P<0.001), V and S
      areas, increase in VO(2) and WR at VT, increase in bFGF (9.21+/-5.82-21.2+/-7.04
      ng/ml, P<0.001), and no change in VEGF (1.45+/-0.72-1.88+/-0.52 ng/ml, P=0.016).
      The stepwise multiple regression analysis revealed that DeltaBMI (beta=-6.052)
      and DeltaVO(2) (beta=2.806) were independently related to DeltabFGF (P<0.001) and
      all other variables including DeltaS area, and DeltaV area, and DeltaWR did not
      enter the equation at significant levels. CONCLUSION: The present study indicated
      a negative correlation between serum bFGF levels and BMI at baseline as well as
      an association of DeltaBMI and DeltaVO(2) with DeltabFGF after exercise
      intervention. The exercise-induced elevation of bFGF may be beneficial in the
      prevention of the atherosclerosis in overweight subjects.

PMID- 14574343
TI  - Moderate physical activity permits acute coupling between serum leptin and
      appetite-satiety measures in obese women.
AB  - OBJECTIVES: To investigate whether moderate physical activity or snack intake
      influence appetite sensations and subsequent food intake in obese women.
      Associations between serum leptin and appetite ratings were also investigated.
      METHODS: In all, 10 obese women (mean age+/-s.d.: 50.0+/-8.5 y; mean body mass
      index (BMI)+/-s.d.: 37.2+/-6.5 kg m(-2)) were submitted in random order to three
      trials: Moderate physical activity (20 min brisk walking), Snack (58.5 g
      chocolate-based) and Control (sitting, TV-watching). Appetite and satiety were
      assessed by visual analogue scales, and serum leptin, blood glucose and plasma
      free fatty acids were measured at baseline, pre- and postintervention and 1 h
      postintervention (ie, before dinner). A buffet-style dinner was provided
      subsequent to the three trials. RESULTS: The moderate physical activity and snack
      intake both produced lower appetite and higher satiety and fullness perceptions,
      compared to control, following the intervention. No significant differences were
      found in subsequent food intake. Serum leptin concentrations did not differ
      between trials. Serum leptin was not associated with appetite or satiety
      sensations at any time during the control or the snack trials, but was correlated
      following moderate physical activity (prospective food consumption r(s)=-0.83,
      P=0.003; hunger r(s)=-0.79, P=0.007; desire to eat r(s)=-0.69, P=0.02; satiety
      r(s)=0.71, P=0.02; fullness r(s)=0.66, P=0.04). These associations were not
      influenced by BMI or fat mass. CONCLUSIONS: Moderate physical activity and snack
      intake suppress the appetite of obese women acutely. The associations between
      circulating leptin and appetite-satiety ratings suggest leptin involvement in
      short-term appetite regulation in response to physical activity-induced factors.

PMID- 14574344
TI  - Sitting time and work patterns as indicators of overweight and obesity in
      Australian adults.
AB  - BACKGROUND: Increasing levels of physical inactivity and sedentariness are
      contributing to the current overweight and obesity epidemic. In this paper, the
      findings of two recent studies are used to explore the relationships between
      sitting time (in transport, work and leisure), physical activity and body mass
      index (BMI) in two contrasting samples of adult Australians. METHODS: Data on
      sitting time, physical activity, BMI and a number of demographic characteristics
      were compared for participants in two studies-529 women who were participants in
      a preschool health promotion project ('mothers'), and 185 men and women who were
      involved in a workplace pedometer study ('workers'). Relationships between age,
      number of children, physical activity, sitting time, BMI, gender and work
      patterns were explored. Logistic regression was used to predict the likelihood of
      being overweight or obese, among participants with different physical activity,
      sitting time and work patterns. RESULTS: The total reported time spent sitting
      per day (across all domains) was almost 6 h less among the mothers than the
      workers (P<0.001), and compared with the mothers, a significantly greater
      proportion of the workers was classified as overweight or obese (BMI > or =25
      kg/m(2)). Univariate analysis found that, compared with men in full-time work,
      women who worked full-time (OR=0.42, CI: 0.24-0.74), part-time (OR=0.35, CI: 0.20
      0.59) or in full-time home duties (OR=0.51, CI: 0.29-0.88) were about half as
      likely to be overweight or obese. Participants who reported high daily levels of
      sitting (> or =7.4 h) were also significantly more likely than those who reported
      'low' levels (<4.7 h/day) to be overweight or obese (OR=1.68, CI: 1.16-2.42).
      Multivariate analysis (including physical activity, work patterns and sitting
      time) confirmed that full-time and part-time working women (but not 'home duties'
      women) were less likely to report BMI > or =25 kg/m(2) than full-time working men
      (full-time: OR=0.44, CI: 0.25-0.78; part-time: OR=0.45, CI: 0.24-0.86), but the
      OR for BMI > or =25 among those in the high sitting category was attenuated
      (OR=1.61, CI 0.96-2.71). CONCLUSIONS: The findings suggest a need for inclusion
      of measures of both activity and inactivity in future studies, so that the
      complex relationships between these behavioural determinants of BMI can be
      clarified.

PMID- 14574345
TI  - Cardiac hypertrophy and diastolic function in physically well trained and in
      obese men.
AB  - OBJECTIVE: The aim of the present study was to compare cardiac hypertrophy and
      diastolic function in extremely obese male patients and physically active adult
      male subjects of similar age (means 43.0-43.4 y). DESIGN: Data of male patients
      referred to our hospital ward in order to reduce their body weight (BW) were
      compared with those of physically active and nonactive healthy males. SUBJECTS:
      The groups contained 21-24 male subjects, very active and moderately active
      subjects taking part in regular competitive or leisure time physical activity
      were in the two athletic groups, severely overweight patients constituted the
      obese group and healthy persons served as controls. MEASUREMENTS: Two
      dimensionally guided M-mode and Doppler recordings. RESULTS: In comparison with
      the controls, obese patients had larger left atrial systolic and left ventricular
      (LV) diastolic internal diameters, LV diastolic wall thickness and muscle mass.
      Of the body size-related indices, only the left atrial systolic diameter index
      was significantly higher. LV systolic and diastolic functions were impaired as
      indicated by a decreased ejection fraction (EF), higher heart rate (HR),
      decreased E/A quotient and increased isovolumetric relaxation time. In the
      physically very active subjects, a thicker LV diastolic wall was seen without LV
      dilatation. Body size-related wall thickness and muscle mass were significantly
      higher than in the controls. EF and HR did not differ from those of the controls.
      CONCLUSION: The most useful help to distinguish between physiological and
      pathological left ventricular hypertrophy can be to investigate diastolic
      functions. The most salient difference appeared in diastolic function, because
      E/A quotient was higher in the very active subjects than in the controls and it
      was the lowest in the obese persons.

PMID- 14574346
TI  - Effect of shift work on body mass index: results of a study performed in 319
      glucose-tolerant men working in a Southern Italian industry.
AB  - OBJECTIVE: To examine the influence of shift work on metabolic and cardiovascular
      risk factors in subjects working in an industry sited in Apulia, Southern Italy.
      DESIGN: Cross-sectional study of metabolic effects of shift work in glucose
      tolerant workers in a chemical industry in southern Italy. SUBJECTS: The subjects
      included 319 glucose tolerant male individuals, aged 35-60 y. MEASUREMENTS:
      Anthropometric parameters (body mass index (BMI) and waist-to-hip ratio (WHR)),
      fasting concentrations of glucose, insulin, and lipids (total cholesterol, HDL
      cholesterol, triglycerides), the sum of glucose levels during 75 g-oral glucose
      tolerance test (Sigma-OGTT), and systolic and diastolic blood pressure (SBP and
      DBP, respectively). RESULTS: The prevalence of obesity was higher among shift
      workers compared to day workers, whereas body fat distribution was not different
      between the two groups. Shift workers had higher BMI than day workers, and shift
      working was associated with BMI, independently of age and work duration. Shift
      workers had significantly higher SBP levels, which were independently influenced
      by BMI, but not by shift work, thus suggesting that the difference in SBP may
      well be mediated by the increased body fatness. CONCLUSION: In workers of an
      industry sited in Southern Italy, shift work may be directly responsible for
      increased body fatness and is indirectly associated with higher blood pressure
      levels and some features of metabolic syndrome.

PMID- 14574347
TI  - Racial differences in glucagon-like peptide-1 (GLP-1) concentrations and insulin
      dynamics during oral glucose tolerance test in obese subjects.
AB  - Obese African-American (AA) subjects have higher resting and stimulated insulin
      concentrations than obese Caucasians (C), which could not be explained by the
      severity of obesity or the degree of insulin sensitivity. We investigated whether
      differences in glucagon-like peptide-1 (GLP-1), the most potent incretin that
      regulates insulin secretion, might explain racial differences in insulin
      response. Accordingly, we measured fasting and stimulated glucose, insulin, and
      GLP-1 levels during a 3-h oral glucose tolerance test (OGTT) in 26 obese C (age
      38+/-2 y, body mass index 44+/-1 kg/m(2)) and 16 obese AA (age 36+/-2 y, BMI 46+/
      2 kg/m(2)) subjects. Corrected insulin response (CIR(30)), a measure of beta-cell
      activity, whole body insulin sensitivity index (WBISI), and area under the curve
      (AUC) for insulin, GLP-1, and C-peptide/insulin ratio were computed from the
      OGTT. Glucose levels, fasting and during the OGTT, were similar between racial
      groups; 32% of the C and 31% of the AA subjects had impaired glucose tolerance.
      With a similar WBISI, AAs had significantly higher CIR(30) (2.3+/-0.4 vs 1.01+/
      0.1), insulin response (IAUC: 23 974+/-4828 vs 14 478+/-1463), and lower insulin
      clearance (0.07+/-0.01 vs 0.11+/-0.01) than C (all, P<0.01). Obese AAs also had
      higher fasting GLP-1 (6.7+/-2.5 vs 4.5+/-1.1) and GLP-1AUC (1174.7+/-412 vs
      822.4+/-191) than C (both, P<0.02). Our results indicate that obese AAs had
      higher concentrations of GLP-1 both at fasting and during the OGTT than obese C.
      The increased GLP-1 concentration could explain the greater insulin concentration
      and the increased prevalence of hyperinsulinemia-associated disorders including
      obesity and type 2 diabetes in AAs.

PMID- 14574348
TI  - Almonds vs complex carbohydrates in a weight reduction program.
AB  - OBJECTIVE: To evaluate the effect of an almond-enriched (high monounsaturated
      fat, MUFA) or complex carbohydrate-enriched (high carbohydrate) formula-based low
      calorie diet (LCD) on anthropometric, body composition and metabolic parameters
      in a weight reduction program. DESIGN: A randomized, prospective 24-week trial in
      a free-living population evaluating two distinct macronutrient interventions on
      obesity and metabolic syndrome-related parameters during weight reduction.
      SUBJECTS: In total, 65 overweight and obese adults (age: 27-79 y, body mass index
      (BMI): 27-55 kg/m(2)). INTERVENTION: A formula-based LCD enriched with 84 g/day
      of almonds (almond-LCD; 39% total fat, 25% MUFA and 32% carbohydrate as percent
      of dietary energy) or self-selected complex carbohydrates (CHO-LCD; 18% total
      fat, 5% MUFA and 53% carbohydrate as percent of dietary energy) featuring
      equivalent calories and protein. MAIN OUTCOME MEASUREMENTS: Various
      anthropometric, body composition and metabolic parameters at baseline, during and
      after 24 weeks of dietary intervention. RESULTS: LCD supplementation with
      almonds, in contrast to complex carbohydrates, was associated with greater
      reductions in weight/BMI (-18 vs -11%), waist circumference (WC) (-14 vs -9%),
      fat mass (FM) (-30 vs -20%), total body water (-8 vs -1%) and systolic blood
      pressure (-11 vs 0%), P=0.0001-0.05. A 62% greater reduction in weight/BMI, 50%
      greater reduction in WC and 56% greater reduction in FM were observed in the
      almond-LCD as compared to the CHO-LCD intervention. Ketone levels increased only
      in the almond-LCD group (+260 vs 0%, P<0.02). High-density lipoprotein
      cholesterol (HDL-C) increased in the CHO-LCD group and decreased in the almond
      LCD group (+15 vs -6%, P=0.05). Glucose, insulin, diastolic blood pressure, total
      cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C) and LDL-C
      to HDL-C ratio decreased significantly to a similar extent in both dietary
      interventions. Homeostasis model analysis of insulin resistance (HOMA-IR)
      decreased in both study groups over time (almond-LCD: -66% and CHO-LCD: -35%,
      P<0.0001). Among subjects with type 2 diabetes, diabetes medication reductions
      were sustained or further reduced in a greater proportion of almond-LCD as
      compared to CHO-LCD subjects (96 vs 50%, respectively) [correction]. CONCLUSION:
      Our findings suggest that an almond-enriched LCD improves a preponderance of the
      abnormalities associated with the metabolic syndrome. Both dietary interventions
      were effective in decreasing body weight beyond the weight loss observed during
      long-term pharmacological interventions; however, the almond-LCD group
      experienced a sustained and greater weight reduction for the duration of the 24
      week intervention. Almond supplementation of a formula-based LCD is a novel
      alternative to self-selected complex carbohydrates and has a potential role in
      reducing the public health implications of obesity.

PMID- 14574349
TI  - Lack of association between central adiposity and lipaemia in UK Sikh men.
AB  - OBJECTIVE: To determine whether the positive statistical associations between
      measures of total and regional adiposity and measures of glucose, insulin and
      triacylglycerol (TAG) metabolism reported in Caucasian men, are also observed in
      UK Sikhs. DESIGN: A matched cross-sectional study in which each volunteer
      provided a blood sample after a 12-h overnight fast and had anthropometric
      measurements taken. SUBJECTS: A total of 55 healthy Caucasian and 55 healthy UK
      Sikh men were recruited. The Caucasian and Sikh men were matched for age (48.7+/
      10.9 and 48.3+/-10.0 y, respectively) and body mass index (BMI) (26.1+/-2.8 and
      26.3+/-3.2 kg/m(2), respectively). MEASUREMENTS: Anthropometric measurements were
      performed to assess total and regional fat depots. The concentrations of plasma
      total cholesterol, high-density cholesterol (HDL-C), low-density cholesterol (LDL
      C) and small dense LDL (LDL3), TAG, glucose, fasting insulin (ins) and
      nonesterified fatty acids (NEFA) were analysed in fasted plasma. Surrogate
      measures of insulin resistance (HOMA-IR) and insulin sensitivity (RQUICKI) were
      calculated from insulin and glucose (HOMA-IR) and insulin, glucose and NEFA
      (RQUICKI) measurements. RESULTS: The Sikh men had significantly higher body fat,
      with the sum of the four skinfold measurements (Ssk) (P=0.0001) and subscapular
      skinfold value (P=0.009) higher compared with the Caucasian men. The Sikh
      volunteers also had characteristics of the metabolic syndrome: lower HDL-C
      (P=0.07), higher TAG (P=0.004), higher % LDL3 (P=0.0001) and insulin resistance
      (P=0.05). Both ethnic groups demonstrated positive correlations between insulin
      and waist circumference (Caucasian: r=0.661, P=0.0001; Sikh: r=0.477, P=0.0001).
      The Caucasian men also demonstrated significant positive correlations between
      central adiposity (r=0.275, P=0.04), other measures of adiposity (BMI and
      suprailiac skinfold) and plasma TAG, whereas the Sikh men showed no correlation
      for central adiposity (r=0.019, ns) and TAG with a trend to a negative
      relationship between other measures (Ssk and suprailiac) which reached near
      significance for subscapular skinfold and TAG (r=-0.246, P=0.007). The expected
      positive association between insulin and TAG was observed in the Caucasian men
      (r=0.318, P=0.04) but not in the Sikh men (r=0.011, ns). CONCLUSIONS: In the
      Caucasian men, the expected positive association between plasma TAG and
      centralized body fat was observed. However, a lack of association between
      centralized, or any other measure of adiposity, and plasma TAG was observed in
      the matched Sikh men, although both ethnic groups showed the positive association
      between centralized body fat and insulin resistance, which was less strong for
      Sikhs. These findings in the Sikh men were not consistent with the hypothesis
      that there is a clear causal relationship between body fat and its distribution,
      insulin resistance, and lipid abnormalities associated with the metabolic
      syndrome, in this ethnic group.

PMID- 14574350
TI  - Change in body mass index from adolescence to young adulthood and increased
      carotid intima-media thickness at 28 years of age: the Atherosclerosis Risk in
      Young Adults study.
AB  - Obesity has become a major health problem in Western societies by increasing the
      risk of atherosclerosis and cardiovascular disease. Although data on tracking of
      body mass index (BMI) are available, little is known about the impact of weight
      change over time on the development of vascular damage. OBJECTIVE: To evaluate
      the relationship between adolescent BMI as well as change in BMI from adolescence
      into young adulthood and cardiovascular risk, as estimated by common carotid
      intima-media thickness (CIMT). DESIGN: Cohort study. SUBJECTS: A total of 750
      healthy young adults, aged 27-30 y, who attended secondary school in Utrecht, the
      Netherlands. MEASUREMENTS: Data on adolescent weight, height, blood pressure and
      puberty stage were available from the original school health records of the
      Municipal Health Service. At young adulthood, a questionnaire on cardiovascular
      risk factors was completed and fasting blood sample was drawn and common CIMT was
      measured. RESULTS: One standard deviation (s.d.) increase in adolescent BMI was
      associated with 2.3 microm [95% confidence interval (CI): 1.3; 3.3] increase in
      mean common CIMT in young adults after adjustment for gender, adolescent age,
      adolescent blood pressure, puberty stage and lumen diameter. Further adjustment
      for adult cardiovascular risk factors did not change the relationship (linear
      regression coefficient=2.1 microm/s.d.; 95% CI: 1.0; 3.1). Adjustment for adult
      BMI attenuated the association (linear regression coefficient=0.9 microm/s.d.;
      95% CI: -0.3; 2.2) as the majority of overweight and obese adolescents remained
      overweight or became obese young adults. Subjects who remained in the upper BMI
      distribution from adolescence into young adulthood had a significantly higher
      common CIMT compared to those who showed relative weight loss over time (mean
      difference 14.7 mum; P<0.001). These latter showed similar CIMT values as
      individuals with constant low BMI. CONCLUSION: Adolescent BMI predicts
      cardiovascular risk, as estimated by common CIMT in young adulthood. Individuals
      who experience the largest increase in BMI and those who remain overweight over
      time have the thickest common CIMT.

PMID- 14574351
TI  - Body mass index in early and mid-adulthood, and subsequent mortality: a
      historical cohort study.
AB  - BACKGROUND: The aim of this study was to investigate the associations between
      body mass index (BMI) in early and mid-adulthood, and BMI change between these
      ages, and mortality. METHODS: Historical cohort study of 629 men, who had height
      and weight measured at the Student Health Service of the University of Glasgow in
      1948-1949 (median age 22 y) and who reported their weight in a postal
      questionnaire in 1963-1966 (median age 38 y). The participants were followed up
      until April 2002 (mean follow-up: 35 y). During this time, 124 men died, 68 of
      cardiovascular disease (CVD) and 33 of cancer. FINDINGS: Mean BMI increased from
      21.4 kg/m(2) (standard deviation (s.d.): 2.2 kg/m(2)) in early adulthood to 24.2
      kg/m(2) (s.d.: 3.0 kg/m(2)) in mid-adulthood. All-cause mortality was associated
      with being overweight (BMI> or =25 kg/m(2)) at age 22 but not at age 38, adjusted
      hazard ratio (HR): 1.85 (95% confidence interval (CI) 1.09-3.13) and 1.05 (95%
      CI: 0.73-1.52), respectively. BMI at age 22 y was more strongly associated with
      CVD mortality than was BMI at age 38 y, adjusted HR(22 y): 2.41 (95% CI: 1.26
      4.60) and HR(38 y): 1.33 (95% CI: 0.82-2.16). There was no clear relationship
      between cancer mortality and BMI at either age: HR(22 y): 0.68 (95% CI: 0.16
      2.91), HR(38 y): 0.90 (95% CI: 0.44-1.84), although relatively few men died of
      cancer in the follow-up period. Similar patterns were seen for obesity (BMI> or
      =30 kg/m(2)) as for being overweight. Analyses of weight patterns indicated
      particularly detrimental effects of overweight persisting from early to mid
      adulthood. CONCLUSIONS: BMI in early adulthood is positively related to CVD
      mortality in later life in men. The risk associated with early adulthood
      adiposity appeared to be greater than that in mid-adulthood. We did not
      demonstrate an association between weight gain and later mortality. These results
      reinforce the need to stem the obesity epidemic in children and young adults.

PMID- 14574352
TI  - Longitudinal changes in risk variables underlying metabolic Syndrome X from
      childhood to young adulthood in female subjects with a history of early menarche:
      the Bogalusa Heart Study.
AB  - OBJECTIVES: To examine the longitudinal changes in adiposity and related risk
      variables of Syndrome X from childhood to young adulthood with respect to early
      onset of menarche. DESIGN: Community-based longitudinal cohort of female subject
      (65% white, 35% blacks subjects) who participated in two or more surveys from
      childhood to young adulthood and had reported their menarcheal age (<12 y, n=437
      vs > or =12 y, n=1042). RESULTS: In childhood (5-11 y), adolescence (12-18 y),
      and young adulthood (19-37 y), females with early menarche displayed
      significantly higher body mass index (BMI) and triceps skinfold thickness; higher
      stature in childhood and adolescence; higher fasting insulin and homeostasis
      model assessment index of insulin resistance (HOMA-IR) in childhood and
      adulthood; and higher fasting glucose in adulthood. Blood pressure and
      lipoprotein variables showed no early menarche-related differences. Longitudinal
      rates of change in BMI (P=0.002), triceps skinfold thickness (P=0.05), insulin
      (P=0.09), and HOMA-IR (P=0.05) were positive and faster among female subjects
      with early menarche; fasting glucose decreased slowly in this group (P=0.006). In
      a multivariate analysis, body fatness and insulin related independently to early
      menarche (P<0.001). This association was stronger in white subjects (P=0.0008).
      In adulthood, the prevalence of clustering of three to four risk factors of
      syndrome X (highest quartile of: (1) BMI, (2) fasting insulin, (3) systolic or
      mean arterial pressure, and (4) total cholesterol to HDL cholesterol or
      triglycerides to HDL cholesterol ratio specific for age, race, and study year)
      was higher among those with early menarche (10.7 vs 6.2%, P=0.002). The odds for
      developing such clustering in adulthood among those with early menarche was 1.54
      (95% CI=1.14-2.07), regardless of race. CONCLUSION: Early menarche is
      characterized by excess body fatness and insulin beginning in early childhood and
      higher prevalence of clustering of adverse levels of risk variables of metabolic
      Syndrome X in young adulthood.

PMID- 14574353
TI  - Self-reported rate of eating correlates with body mass index in 18-y-old Japanese
      women.
AB  - OBJECTIVE: To examine associations between rate of eating and macronutrient and
      dietary fiber intake, and body mass index (BMI). DESIGN: Cross-sectional study.
      SUBJECTS: A total of 1695 18-y-old female Japanese dietetic students.
      MEASUREMENTS: Macronutrient intake (protein, carbohydrate, and fat) and dietary
      fiber intake were assessed over a 1-month period with a validated, self
      administered, diet history questionnaire. Body height and weight and rate of
      eating (according to five categories) were self-reported. RESULTS: Among the
      nutrients examined, only dietary fiber intake weakly, but significantly, and
      negatively correlated with BMI in a multiple regression analysis. The rate of
      eating showed a significant and positive correlation with BMI. The mean BMI was
      higher by 2.2, 1.5, 1.0, and 0.5 kg/m(2) in the 'very fast', 'relatively fast',
      'medium', and 'relatively slow' groups, respectively, compared with the 'very
      slow' rate of eating group. This correlation remained evident after adjustment
      for nutrient intake. CONCLUSIONS: Rate of eating showed a significant and
      positive correlation with BMI, whereas only dietary fiber intake showed a weak
      correlation with BMI.

PMID- 14574354
TI  - Risk factors for childhood overweight in 6- to 7-y-old Hong Kong children.
AB  - OBJECTIVE: To identify risk factors for overweight in Hong Kong children aged 6-7
      y. DESIGN: Case-control study. SETTING: Student Health Service Centres, Hong
      Kong. SUBJECTS: A total of 343 Hong Kong Chinese children aged 6-7 y old
      categorised into three groups, an overweight group (> or =92 nd centile for BMI),
      a normal middle-weight group (45th-55th centile for BMI) and a normal low-weight
      group (< or =8th centile for BMI). MEASUREMENTS: Subjects and their
      parents/caregivers were interviewed at home. Data on lifestyle habits, dietary
      habits, family structure and demographic background were collected by
      questionnaire. A 3-day dietary record was administrated by the parents/caregivers
      to assess dietary intake of the children. RESULTS: Logistic regression analyses
      (overweight group compared with middle-weight plus low-weight groups) showed that
      childhood overweight was significantly associated with parental obesity (BMI > or
      =25 kg/m(2), Asian reference) (paternal: OR=2.66, 95% CI=1.51-4.70; maternal:
      5.07, 2.62-9.79) but not parental overweight (BMI=23-25 kg/m(2)). After
      adjustment for parental obesity, the odds ratio for childhood overweight was
      increased by birth weight (<3.0 kg as reference, 3.0-3.5 kg: 2.13, 1.18-3.84; >
      or =3.5 kg: 4.89, 2.49-9.60) and decreased by sleeping duration (<9 h/day as
      reference, 9-11 h/day: 0.54, 0.30-0.97; > or =11 h/day: 0.31, 0.11-0.87).
      Childhood overweight was also significantly associated with higher energy
      consumption (2.62, 1.20-5.74) and having a father who was a current smoker (2.08,
      1.25-3.46). CONCLUSIONS: Although healthy diet and regular exercise will remain
      the cornerstones of obesity management in children, our data support the view
      that education about maintaining a healthy weight could be introduced much
      earlier in those families with high-risk children, as indicated by high parental
      BMI or high birth weight. The utility and practicality of such an approach should
      be carefully evaluated before becoming part of any public health policy. Further
      study of the role of short sleeping duration and parental smoking on childhood
      obesity development is warranted.

PMID- 14574355
TI  - Differential clinical expression of multiple symmetric lipomatosis in men and
      women.
AB  - BACKGROUND: Multiple symmetric lipomatosis (MSL) is a rare disease characterised
      by the growth of uncapsulated masses of adipose tissue. MSL is associated with
      high ethanol intake and complicated by somatic and autonomic neuropathy and the
      infiltration of adipose tissue at the mediastinal level. To date, the disease is
      considered as largely more prevalent in men. OBJECTIVE: To provide a detailed
      description of the clinical aspects of MSL in women. PATIENTS: A total of 11
      women and 58 men with MSL. MEASUREMENTS: Morphological aspect of patient,
      location of the lipomatous masses, alcohol intake, extension of lipomatous tissue
      to the mediastinum, association with somatic and autonomic neuropathy, and
      metabolic profile. RESULTS: All female patients had the obesity-like appearance
      of type II MSL and the most frequent locations of lipomatous masses in women were
      at the proximal arms (90.9%) and legs (54.5%). Very few female patients (27.3%)
      presented with the submental deposition of lipomatous tissue typical of both type
      I (97.3%; P<0.001) and type II (66.7%; P<0.05) male subjects. An extension of the
      lipomatus tissue around the upper airways, associated with compression or
      dislocation of deeply located mediastinal structures, was observed less
      frequently in women than in men. The presence of a high ethanol intake, the
      association with somatic and autonomic neuropathy and the occurrence of a
      characteristic metabolic pattern (high HDL-cholesterol, low LDL-cholesterol, high
      uric acid) were similar in men and in women. CONCLUSIONS: Female patients with
      MSL had a sex-specific morphological aspect, characterised by a low occurrence of
      the typical 'Madelung collar' and a usual obesity-like appearance.

PMID- 14574356
TI  - Effects of outcome-driven insurance reimbursement on short-term weight control.
AB  - CONTEXT: Although most health insurers exclude coverage of weight control
      therapy, one local insurer offered partial reimbursement of the cost of a weight
      control program, using an incentive plan. OBJECTIVE: To determine whether outcome
      driven insurer-based reimbursement improves participation in a weight control
      program and short-term weight loss outcomes. DESIGN: Cohort follow-up study
      between January 1998 and February 2001. SETTING: Community weight management
      program operated by an academic medical center. SUBJECTS: Obese participants who
      had the potential for reimbursement (Group A, n=25) and participants in the same
      program classes (Group B, n=100) who had no possibility for reimbursement.
      Subjects in Group B were selected from among 206 potential participants using a
      propensity score to match them with subjects in Group A on age, gender,
      ethnicity, starting BMI, starting weight, and educational, economic, and
      demographic variables. INTERVENTION: Group lifestyle-based weight management
      program. The insurer reimbursed half the cost of the program to obese
      participants who met minimum weight criteria, paid the program fee at enrollment,
      attended > or =10 of the 12 classes, and lost > or =6% of initial body weight
      after 12 weeks. MAIN OUTCOME MEASURES: Participation rates and weight loss
      outcomes. RESULTS: Group A subjects attended significantly more classes (mean+/
      s.d.: 10.1+/-1.8 vs 8.2+/-2.5, P<0.001) and lost more weight than Group B
      subjects (6.1+/-3.1 vs 3.7+/-3.6%, P=0.002). While 84% of Group A subjects
      attended > or =10 classes, only 37% of Group B subjects did so (P<0.001); 56% of
      Group A subjects lost > or =6% of body weight, but only 20% of Group B subjects
      did so (P<0.001); 56% of Group A subjects achieved both the class attendance and
      weight loss goals, but only 14% of Group B subjects did so (P<0.001). Logistic
      regression estimated that Group A subjects had 8.2 times the odds of attending >
      or =10 classes and 4.5 times the odds of losing > or =6% of body weight of Group
      B subjects, after controlling for class attendance. CONCLUSIONS: Insurer-based
      reimbursement that is contingent upon initial financial commitment on the part of
      the patient, consistent program participation, and successful weight loss is
      associated with significantly better short-term weight control outcomes.

PMID- 14574357
TI  - Body mass index and asthma among Mexican adults: the effect of using self
      reported vs measured weight and height.
AB  - Several recent studies have demonstrated a positive association between obesity
      and asthma among women but not men. The present study examines the effect of
      misclassification of body mass index (BMI) in the association between obesity and
      asthma by gender. This cross-sectional analysis included a total sample of 961
      Mexican adults. Use of measured BMI revealed that obesity (BMI >30 kg/m(2)) was a
      risk factor for asthma diagnosis in both men (OR, 2.5; 95% CI, 1.1-5.9) and women
      (OR, 2.3; 95% CI, 1.5-3.8). In contrast, use of self-reported BMI showed that
      only women (OR, 1.7; 95% CI, 1.1-2.7) and not men (OR, 1.3; 95% CI, 0.6-2.9) were
      at increased risk of asthma diagnosis. Use of self-reported BMI substantially
      underestimated the prevalence of obesity; this bias was not related to asthma per
      se but was mainly due to obesity. Therefore, misclassification of BMI obscured
      the relationship between obesity and asthma to a greater extent among men than
      among women since obesity prevalence in the general population was higher among
      men. Measurement bias merits greater attention in future research on obesity and
      asthma.

PMID- 14574359
TI  - Genetic information and testing in insurance and employment: technical, social
      and ethical issues.

PMID- 14574358
TI  - Success rate of Orlistat in primary-care practice is limited by failure to follow
      prescribing recommendations: the referral letter content vs clinical reality.
AB  - Numerous referrals to our Obesity Unit state that 'treatment with Orlistat did
      not work'. This surprised us, since Orlistat has been well documented to result
      in long-term sustained moderate weight loss. A simple questionnaire to 70 such
      patients, however, revealed that in many cases the referral physician had not
      observed basic rules and regulations, nor given appropriate information on
      Orlistat use.

PMID- 14574360
TI  - Population genetic screening programmes: technical, social and ethical issues.

PMID- 14574361
TI  - Provision of genetic services in Europe: current practices and issues.

PMID- 14574362
TI  - Data storage and DNA banking for biomedical research: technical, social and
      ethical issues.

PMID- 14574363
TI  - Valproate and GABAergic system effects.

PMID- 14574366
TI  - Pharmacogenetics to come.

PMID- 14574367
TI  - New access for agriculture.

PMID- 14574365
TI  - Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor
      proliferation.
AB  - Stem cells persist throughout life by self-renewing in numerous tissues including
      the central and peripheral nervous systems. This raises the issue of whether
      there is a conserved mechanism to effect self-renewing divisions. Deficiency in
      the polycomb family transcriptional repressor Bmi-1 leads to progressive
      postnatal growth retardation and neurological defects. Here we show that Bmi-1 is
      required for the self-renewal of stem cells in the peripheral and central nervous
      systems but not for their survival or differentiation. The reduced self-renewal
      of Bmi-1-deficient neural stem cells leads to their postnatal depletion. In the
      absence of Bmi-1, the cyclin-dependent kinase inhibitor gene p16Ink4a is
      upregulated in neural stem cells, reducing the rate of proliferation. p16Ink4a
      deficiency partially reverses the self-renewal defect in Bmi-1-/- neural stem
      cells. This conserved requirement for Bmi-1 to promote self-renewal and to
      repress p16Ink4a expression suggests that a common mechanism regulates the self
      renewal and postnatal persistence of diverse types of stem cell. Restricted
      neural progenitors from the gut and forebrain proliferate normally in the absence
      of Bmi-1. Thus, Bmi-1 dependence distinguishes stem cell self-renewal from
      restricted progenitor proliferation in these tissues.

PMID- 14574368
TI  - Biosafety trials darken outlook for transgenic crops in Europe.

PMID- 14574369
TI  - Drugs bust reveals athletes' secret steroid.

PMID- 14574370
TI  - Open access wins German support.

PMID- 14574371
TI  - Fish farms' threat to salmon stocks exposed.

PMID- 14574372
TI  - Opossum hops over kangaroo to top of genome list.

PMID- 14574373
TI  - Biologists seek havens for species at risk.

PMID- 14574374
TI  - Standards-lab staff up in arms over military link.

PMID- 14574376
TI  - The rough guide to the genome.

PMID- 14574377
TI  - With your genes? Take one of these, three times a day.

PMID- 14574378
TI  - Unnatural coverage of Chernobyl tragedy.

PMID- 14574379
TI  - India's mission to the Moon is worthwhile.

PMID- 14574380
TI  - Bioethics: role of religion cannot be ignored.

PMID- 14574381
TI  - Bioethics needs a distinct voice if it is to aid science.

PMID- 14574390
TI  - Genomics: six is seventh.

PMID- 14574392
TI  - Applied physics: to catch a photon.

PMID- 14574393
TI  - Genetics: secrets of a porkier porker.

PMID- 14574394
TI  - Stem cells: interactive niches.

PMID- 14574395
TI  - Metabolism: it's in the genes.

PMID- 14574396
TI  - Cancer: a twist in a hedgehog's tale.

PMID- 14574397
TI  - Earth science: how do your mountains grow?

PMID- 14574398
TI  - Evolution: ending incongruence.

PMID- 14574399
TI  - Life history: changing sex at the same relative body size.

PMID- 14574400
TI  - Ancient materials: analysis of a pharaonic embalming tar.

PMID- 14574401
TI  - The nature of human altruism.
AB  - Some of the most fundamental questions concerning our evolutionary origins, our
      social relations, and the organization of society are centred around issues of
      altruism and selfishness. Experimental evidence indicates that human altruism is
      a powerful force and is unique in the animal world. However, there is much
      individual heterogeneity and the interaction between altruists and selfish
      individuals is vital to human cooperation. Depending on the environment, a
      minority of altruists can force a majority of selfish individuals to cooperate
      or, conversely, a few egoists can induce a large number of altruists to defect.
      Current gene-based evolutionary theories cannot explain important patterns of
      human altruism, pointing towards the importance of both theories of cultural
      evolution as well as gene-culture co-evolution.

PMID- 14574402
TI  - Cenozoic climate change as a possible cause for the rise of the Andes.
AB  - Causal links between the rise of a large mountain range and climate have often
      been considered to work in one direction, with significant uplift provoking
      climate change. Here we propose a mechanism by which Cenozoic climate change
      could have caused the rise of the Andes. Based on considerations of the force
      balance in the South American lithosphere, we suggest that the height of, and
      tectonics in, the Andes are strongly controlled both by shear stresses along the
      plate interface in the subduction zone and by buoyancy stress contrasts between
      the trench and highlands, and shear stresses in the subduction zone depend on the
      amount of subducted sediments. We propose that the dynamics of subduction and
      mountain-building in this region are controlled by the processes of erosion and
      sediment deposition, and ultimately climate. In central South America, climate
      controlled sediment starvation would then cause high shear stress, focusing the
      plate boundary stresses that support the high Andes.

PMID- 14574403
TI  - Genome-scale approaches to resolving incongruence in molecular phylogenies.
AB  - One of the most pervasive challenges in molecular phylogenetics is the
      incongruence between phylogenies obtained using different data sets, such as
      individual genes. To systematically investigate the degree of incongruence, and
      potential methods for resolving it, we screened the genome sequences of eight
      yeast species and selected 106 widely distributed orthologous genes for
      phylogenetic analyses, singly and by concatenation. Our results suggest that data
      sets consisting of single or a small number of concatenated genes have a
      significant probability of supporting conflicting topologies. By contrast,
      analyses of the entire data set of concatenated genes yielded a single, fully
      resolved species tree with maximum support. Comparable results were obtained with
      a concatenation of a minimum of 20 genes; substantially more genes than commonly
      used but a small fraction of any genome. These results have important
      implications for resolving branches of the tree of life.

PMID- 14574405
TI  - The formation of the first low-mass stars from gas with low carbon and oxygen
      abundances.
AB  - The first stars in the Universe are predicted to have been much more massive than
      the Sun. Gravitational condensation, accompanied by cooling of the primordial gas
      via molecular hydrogen, yields a minimum fragmentation scale of a few hundred
      solar masses. Numerical simulations indicate that once a gas clump acquires this
      mass it undergoes a slow, quasi-hydrostatic contraction without further
      fragmentation; lower-mass stars cannot form. Here we show that as soon as the
      primordial gas--left over from the Big Bang--is enriched by elements ejected from
      supernovae to a carbon or oxygen abundance as small as approximately 0.01-0.1 per
      cent of that found in the Sun, cooling by singly ionized carbon or neutral oxygen
      can lead to the formation of low-mass stars by allowing cloud fragmentation to
      smaller clumps. This mechanism naturally accommodates the recent discovery of
      solar-mass stars with unusually low iron abundances (10(-5.3) solar) but with
      relatively high (10(-1.3) solar) carbon abundance. The critical abundances that
      we derive can be used to identify those metal-poor stars in our Galaxy with
      elemental patterns imprinted by the first supernovae. We also find that the
      minimum stellar mass at early epochs is partially regulated by the temperature of
      the cosmic microwave background.

PMID- 14574406
TI  - A coherent three-dimensional Fermi surface in a high-transition-temperature
      superconductor.
AB  - All conventional metals are known to possess a three-dimensional Fermi surface,
      which is the locus in reciprocal space of the long-lived electronic excitations
      that govern their electronic properties at low temperatures. These excitations
      should have well-defined momenta with components in all three dimensions. The
      high-transition-temperature (high-T(c)) copper oxide superconductors have
      unusual, highly two-dimensional properties above the superconducting transition.
      This, coupled with a lack of unambiguous evidence for a three-dimensional Fermi
      surface, has led to many new and exotic models for the underlying electronic
      ground state. Here we report the observation of polar angular magnetoresistance
      oscillations in the overdoped superconductor Tl2Ba2CuO6+delta in high magnetic
      fields, which firmly establishes the existence of a coherent three-dimensional
      Fermi surface. Analysis of the oscillations reveals that at certain symmetry
      points, however, this surface is strictly two-dimensional. This striking form of
      the Fermi surface topography, long-predicted by electronic band structure
      calculations, provides a natural explanation for a wide range of anisotropic
      properties both in the normal and superconducting states. Our data reveal that,
      despite their extreme electrical anisotropy, the high-T(c) materials at high
      doping levels can be understood within a framework of conventional three
      dimensional metal physics.

PMID- 14574407
TI  - A broadband superconducting detector suitable for use in large arrays.
AB  - Cryogenic detectors are extremely sensitive and have a wide variety of
      applications (particularly in astronomy), but are difficult to integrate into
      large arrays like a modern CCD (charge-coupled device) camera. As current
      detectors of the cosmic microwave background (CMB) already have sensitivities
      comparable to the noise arising from the random arrival of CMB photons, the
      further gains in sensitivity needed to probe the very early Universe will have to
      arise from large arrays. A similar situation is encountered at other wavelengths.
      Single-pixel X-ray detectors now have a resolving power of DeltaE < 5 eV for
      single 6-keV photons, and future X-ray astronomy missions anticipate the need for
      1,000-pixel arrays. Here we report the demonstration of a superconducting
      detector that is easily fabricated and can readily be incorporated into such an
      array. Its sensitivity is already within an order of magnitude of that needed for
      CMB observations, and its energy resolution is similarly close to the targets
      required for future X-ray astronomy missions.

PMID- 14574404
TI  - The DNA sequence and analysis of human chromosome 6.
AB  - Chromosome 6 is a metacentric chromosome that constitutes about 6% of the human
      genome. The finished sequence comprises 166,880,988 base pairs, representing the
      largest chromosome sequenced so far. The entire sequence has been subjected to
      high-quality manual annotation, resulting in the evidence-supported
      identification of 1,557 genes and 633 pseudogenes. Here we report that at least
      96% of the protein-coding genes have been identified, as assessed by multi
      species comparative sequence analysis, and provide evidence for the presence of
      further, otherwise unsupported exons/genes. Among these are genes directly
      implicated in cancer, schizophrenia, autoimmunity and many other diseases.
      Chromosome 6 harbours the largest transfer RNA gene cluster in the genome; we
      show that this cluster co-localizes with a region of high transcriptional
      activity. Within the essential immune loci of the major histocompatibility
      complex, we find HLA-B to be the most polymorphic gene on chromosome 6 and in the
      human genome.

PMID- 14574408
TI  - Imaging coexisting fluid domains in biomembrane models coupling curvature and
      line tension.
AB  - Lipid bilayer membranes--ubiquitous in biological systems and closely associated
      with cell function--exhibit rich shape-transition behaviour, including bud
      formation and vesicle fission. Membranes formed from multiple lipid components
      can laterally separate into coexisting liquid phases, or domains, with distinct
      compositions. This process, which may resemble raft formation in cell membranes,
      has been directly observed in giant unilamellar vesicles. Detailed theoretical
      frameworks link the elasticity of domains and their boundary properties to the
      shape adopted by membranes and the formation of particular domain patterns, but
      it has been difficult to experimentally probe and validate these theories. Here
      we show that high-resolution fluorescence imaging using two dyes preferentially
      labelling different fluid phases directly provides a correlation between domain
      composition and local membrane curvature. Using freely suspended membranes of
      giant unilamellar vesicles, we are able to optically resolve curvature and line
      tension interactions of circular, stripe and ring domains. We observe long-range
      domain ordering in the form of locally parallel stripes and hexagonal arrays of
      circular domains, curvature-dependent domain sorting, and membrane fission into
      separate vesicles at domain boundaries. By analysing our observations using
      available membrane theory, we are able to provide experimental estimates of
      boundary tension between fluid bilayer domains.

PMID- 14574409
TI  - Cool Indonesian throughflow as a consequence of restricted surface layer flow.
AB  - Approximately 10 million m3 x s(-1) of water flow from the Pacific Ocean into the
      Indian Ocean through the Indonesian seas. Within the Makassar Strait, the primary
      pathway of the flow, the Indonesian throughflow is far cooler than estimated
      earlier, as pointed out recently on the basis of ocean current and temperature
      measurements. Here we analyse ocean current and stratification data along with
      satellite-derived wind measurements, and find that during the boreal winter
      monsoon, the wind drives buoyant, low-salinity Java Sea surface water into the
      southern Makassar Strait, creating a northward pressure gradient in the surface
      layer of the strait. This surface layer 'freshwater plug' inhibits the warm
      surface water from the Pacific Ocean from flowing southward into the Indian
      Ocean, leading to a cooler Indian Ocean sea surface, which in turn may weaken the
      Asian monsoon. The summer wind reversal eliminates the obstructing pressure
      gradient, by transferring more-saline Banda Sea surface water into the southern
      Makassar Strait. The coupling of the southeast Asian freshwater budget to the
      Pacific and Indian Ocean surface temperatures by the proposed mechanism may
      represent an important negative feedback within the climate system.

PMID- 14574410
TI  - Independent rate and temporal coding in hippocampal pyramidal cells.
AB  - In the brain, hippocampal pyramidal cells use temporal as well as rate coding to
      signal spatial aspects of the animal's environment or behaviour. The temporal
      code takes the form of a phase relationship to the concurrent cycle of the
      hippocampal electroencephalogram theta rhythm. These two codes could each
      represent a different variable. However, this requires the rate and phase to vary
      independently, in contrast to recent suggestions that they are tightly coupled,
      both reflecting the amplitude of the cell's input. Here we show that the time of
      firing and firing rate are dissociable, and can represent two independent
      variables: respectively the animal's location within the place field, and its
      speed of movement through the field. Independent encoding of location together
      with actions and stimuli occurring there may help to explain the dual roles of
      the hippocampus in spatial and episodic memory, or may indicate a more general
      role of the hippocampus in relational/declarative memory.

PMID- 14574411
TI  - A regulatory mutation in IGF2 causes a major QTL effect on muscle growth in the
      pig.
AB  - Most traits and disorders have a multifactorial background indicating that they
      are controlled by environmental factors as well as an unknown number of
      quantitative trait loci (QTLs). The identification of mutations underlying QTLs
      is a challenge because each locus explains only a fraction of the phenotypic
      variation. A paternally expressed QTL affecting muscle growth, fat deposition and
      size of the heart in pigs maps to the IGF2 (insulin-like growth factor 2) region.
      Here we show that this QTL is caused by a nucleotide substitution in intron 3 of
      IGF2. The mutation occurs in an evolutionarily conserved CpG island that is
      hypomethylated in skeletal muscle. The mutation abrogates in vitro interaction
      with a nuclear factor, probably a repressor, and pigs inheriting the mutation
      from their sire have a threefold increase in IGF2 messenger RNA expression in
      postnatal muscle. Our study establishes a causal relationship between a single
      base-pair substitution in a non-coding region and a QTL effect. The result
      supports the long-held view that regulatory mutations are important for
      controlling phenotypic variation.

PMID- 14574412
TI  - Identification of the haematopoietic stem cell niche and control of the niche
      size.
AB  - Haematopoietic stem cells (HSCs) are a subset of bone marrow cells that are
      capable of self-renewal and of forming all types of blood cells (multi
      potential). However, the HSC 'niche'--the in vivo regulatory microenvironment
      where HSCs reside--and the mechanisms involved in controlling the number of adult
      HSCs remain largely unknown. The bone morphogenetic protein (BMP) signal has an
      essential role in inducing haematopoietic tissue during embryogenesis. We
      investigated the roles of the BMP signalling pathway in regulating adult HSC
      development in vivo by analysing mutant mice with conditional inactivation of BMP
      receptor type IA (BMPRIA). Here we show that an increase in the number of spindle
      shaped N-cadherin+CD45- osteoblastic (SNO) cells correlates with an increase in
      the number of HSCs. The long-term HSCs are found attached to SNO cells. Two
      adherens junction molecules, N-cadherin and beta-catenin, are asymmetrically
      localized between the SNO cells and the long-term HSCs. We conclude that SNO
      cells lining the bone surface function as a key component of the niche to support
      HSCs, and that BMP signalling through BMPRIA controls the number of HSCs by
      regulating niche size.

PMID- 14574413
TI  - Osteoblastic cells regulate the haematopoietic stem cell niche.
AB  - Stem cell fate is influenced by specialized microenvironments that remain poorly
      defined in mammals. To explore the possibility that haematopoietic stem cells
      derive regulatory information from bone, accounting for the localization of
      haematopoiesis in bone marrow, we assessed mice that were genetically altered to
      produce osteoblast-specific, activated PTH/PTHrP receptors (PPRs). Here we show
      that PPR-stimulated osteoblastic cells that are increased in number produce high
      levels of the Notch ligand jagged 1 and support an increase in the number of
      haematopoietic stem cells with evidence of Notch1 activation in vivo.
      Furthermore, ligand-dependent activation of PPR with parathyroid hormone (PTH)
      increased the number of osteoblasts in stromal cultures, and augmented ex vivo
      primitive haematopoietic cell growth that was abrogated by gamma-secretase
      inhibition of Notch activation. An increase in the number of stem cells was
      observed in wild-type animals after PTH injection, and survival after bone marrow
      transplantation was markedly improved. Therefore, osteoblastic cells are a
      regulatory component of the haematopoietic stem cell niche in vivo that
      influences stem cell function through Notch activation. Niche constituent cells
      or signalling pathways provide pharmacological targets with therapeutic potential
      for stem-cell-based therapies.

PMID- 14574415
TI  - Targets of the cyclin-dependent kinase Cdk1.
AB  - The events of cell reproduction are governed by oscillations in the activities of
      cyclin-dependent kinases (Cdks). Cdks control the cell cycle by catalysing the
      transfer of phosphate from ATP to specific protein substrates. Despite their
      importance in cell-cycle control, few Cdk substrates have been identified. Here,
      we screened a budding yeast proteomic library for proteins that are directly
      phosphorylated by Cdk1 in whole-cell extracts. We identified about 200 Cdk1
      substrates, several of which are phosphorylated in vivo in a Cdk1-dependent
      manner. The identities of these substrates reveal that Cdk1 employs a global
      regulatory strategy involving phosphorylation of other regulatory molecules as
      well as phosphorylation of the molecular machines that drive cell-cycle events.
      Detailed analysis of these substrates is likely to yield important insights into
      cell-cycle regulation.

PMID- 14574414
TI  - Yip3 catalyses the dissociation of endosomal Rab-GDI complexes.
AB  - Human cells contain more than 60 small G proteins of the Rab family, which are
      localized to the surfaces of distinct membrane compartments and regulate
      transport vesicle formation, motility, docking and fusion. Prenylated Rabs also
      occur in the cytosol bound to GDI (guanine nucleotide dissociation inhibitor),
      which binds to Rabs in their inactive state. Prenyl Rab-GDI complexes contain all
      of the information necessary to direct Rab delivery onto distinct membrane
      compartments. The late endosomal, prenyl Rab9 binds GDI with very high affinity,
      which led us to propose that there might be a 'GDI-displacement factor' to
      catalyse dissociation of Rab-GDI complexes and to enable transfer of Rabs from
      GDI onto membranes. Indeed, we have previously shown that endosomal membranes
      contain a proteinaceous factor that can act in this manner. Here we show that the
      integral membrane protein, Yip3, acts catalytically to dissociate complexes of
      endosomal Rabs bound to GDI, and to deliver them onto membranes. We propose that
      the conserved Yip proteins serve as GDI-displacement factors for the targeting of
      Rab GTPases in eukaryotic cells.

PMID- 14574416
TI  - Seeing is believing.

PMID- 14574417
TI  - Lighting up the body.

PMID- 14574418
TI  - Easing the strain.

PMID- 14574419
TI  - High throughput goes 3D.

PMID- 14574422
TI  - Rewarding experience.

PMID- 14574420
TI  - Scanning the surface.

PMID- 14574423
TI  - In search of form and function.
AB  - On the genetics timeline, the first complete sequence of a free-living organism,
      that of the bacterium Haemophilus influenzae in 1995, was finished 130 years
      after Gregor Mendel published the results of his famous pea-breeding experiment.
      Since that sequence, others have followed thick and fast, including those of the
      nematode Caenorhabditis elegans, the fruitfly, humans and now the dog. But each
      sequence alone cannot provide researchers with much information about the
      organism. For that, they have to go through the painstaking process of knocking
      out genes, one at a time, and observing how these deletions affect biological
      function.

PMID- 14574424
TI  - Building bridges.
AB  - When high-throughput screening of proteins and genes made its debut, it was the
      darling of industry--but new academic facilities are now being set up to make the
      expensive technology involved available to researchers. As a result, new
      institutes are recruiting scientists to liaise between academia and industry; and
      industry, in turn, continues to seek graduates and postdocs--as long as they are
      fresh thinkers with multiple skills. In addition, centres are being set up to
      train students in the latest technologies.

PMID- 14574425
TI  - Posterior encephalopathy with vasospasm: MRI and angiography.
AB  - Posterior encephalopathy is characterised by headache, impairment of
      consciousness, seizures and progressive visual loss. MRI shows bilateral,
      predominantly posterior, cortical and subcortical lesions with a distribution.
      Our aim was to analyse the MRI lesion pattern and angiographic findings because
      the pathophysiology of posterior encephalopathy is incompletely understood. We
      report three patients with clinical and imaging findings consistent with
      posterior encephalopathy who underwent serial MRI including diffusion-weighted
      imaging (DWI) and construction of apparent diffusion coefficient (ADC) maps, and
      four-vessel digital subtraction angiography (DSA). DWI revealed symmetrical
      subcortical and cortical parieto-occipital high signal. High and also low ADCs
      indicated probable vasogenic and cytotoxic oedema. On follow-up there was focal
      cortical laminar necrosis, while the white-matter lesions resolved almost
      completely, except in the arterial border zones. DSA revealed diffuse arterial
      narrowing, slightly more marked in the posterior circulation. These findings
      suggest that posterior encephalopathy may in some cases be due to diffuse, severe
      vasospasm affecting especially in the parieto-occipital grey matter, with its
      higher vulnerability to ischemia. Cerebral vasospasm due to digitoxin
      intoxication, resulting in posterior encephalopathy, has not yet been described
      previously.

PMID- 14574427
TI  - Tactile stimulus predictability modulates activity in a tactile-motor cortical
      network.
AB  - Manipulating objects in the hand requires the continuous transformation of
      sensory input into appropriate motor behaviour. Using a novel vibrotactile device
      combined with fMRI, the cortical network associated with tactile sensorimotor
      transformations was investigated. Continuous tactile stimuli were delivered in a
      random or predictable pattern to the second digit on the right hand of all
      subjects. To better distinguish sensory and motor processes, subjects were
      instructed to make proportionate motor gripping responses with their left hand. A
      consistent cortical network of activation was revealed that included the
      supplementary motor, dorsal and ventral premotor, posterior parietal, primary and
      secondary somatosensory and primary motor cortex. Tracking the unpredictable
      versus predictable tactile stimulus led to greater delays in motor responses and
      to increased performance errors. Cortical effects due to stimulus predictability
      were observed in several components of the network, though it was most evident as
      increased cortical activation in frontal motor regions during tracking of
      unpredictable tactile stimuli. In contrast to the proposed hypotheses, primary
      and secondary somatosensory cortices contralateral to tactile input did not
      reveal enhanced responses during unpredictable tracking. Facilitation during
      unpredictable tracking was also observed in primary somatosensory cortex
      contralateral to motor responses, the receptive site for movement-related
      afference. The present study provides a novel and controlled approach to
      investigate the loci associated with tactile-motor processing and to measure the
      task-specific effect of stimulus predictability on network components.

PMID- 14574428
TI  - Spatial representation of corticofugal input in the inferior colliculus: a
      multicontact silicon probe approach.
AB  - The inferior colliculus (IC) is a well-established target of descending
      projections from the auditory cortex (AC). However, our understanding of these
      pathways has been limited by an incomplete picture of their functional influence
      within the three-dimensional space of the IC. Our goal was to study the
      properties and spatial representation of corticofugal input in the IC of guinea
      pigs with a high degree of spatial resolution. We systematically mapped neural
      activity in the IC using two types of silicon substrate probes that allow for
      simultaneous recording at multiple neural sites. One probe provided a high
      resolution in the dorsal-ventral plane and the other provided spatial resolution
      in the medial-lateral plane. Electrical stimulation of the ipsilateral AC
      produced excitatory responses in the IC with thresholds usually below 5-10
      microA. First spike latencies were predominantly in the 6-20 ms range, although
      latencies from 3-5 ms were also observed. Broadly distributed unimodal spike
      patterns with modal latencies greater than 30 ms were occasionally seen. The
      excitatory responses to cortical stimulation were mostly unimodal and
      occasionally bimodal with a wide range of spike distribution patterns and
      response durations. Excitation was often followed by suppression of spontaneous
      activity. Suppression of acoustic responses was observed even when there was
      little or no response to electrical stimulation, suggesting spatial-temporal
      integration. A few of the responding neurons showed purely inhibitory responses
      to electrical stimulation, suggesting that there are disynaptic routes of
      corticocollicular inhibition. Detailed spatial mapping revealed that the response
      patterns and their durations had a characteristic spatial distribution in the IC.

PMID- 14574429
TI  - Properties of human motor units after prolonged activity at a constant firing
      rate.
AB  - The primary purpose of this study was to examine if there are changes in the
      intrinsic properties of spinal motoneurons after prolonged submaximal
      contractions. To do this, we assessed whether or not the synaptic drive to
      motoneurons needs to increase in order to maintain a constant firing rate of a
      motor unit. Recruitment of new units and an increase in total electromyographic
      (EMG) activity of the muscle of interest were taken as estimates of an increase
      in synaptic drive. Subjects were asked to maintain a constant firing rate of a
      clearly identifiable (targeted) motor unit from the first dorsal interosseous
      muscle for approximately 10 min, while surface EMG and force were recorded
      simultaneously. For the 60 units studied, the duration of the constant-firing
      rate period ranged from 73 to 1,140 s (448 +/- 227 s; mean +/- SD). There was a
      significant increase ( t-test, p<0.001) in the magnitude of mean surface EMG, and
      DC force while the targeted motoneuron maintained a constant rate suggesting an
      increase in the net excitatory input to the motoneuron pool. Changes occurring
      simultaneously in other parameters, namely, variability in interspike interval,
      magnitude of force fluctuations, the duration of motor unit action potentials,
      and the median power frequency of surface EMG were also computed. The firing
      rates of 16 concurrently firing motoneurons, not controlled by the subject,
      remained constant. The key finding of this study is that after prolonged
      activity, a motoneuron requires a stronger excitatory input to maintain its
      firing rate. Additional results are indicative of significant changes in the
      characteristics of the synaptic inputs, changes at the neuromuscular junction
      (both pre- and postsynaptic regions) and the sarcolemma.

PMID- 14574432
TI  - New mathematical models with associated equations for isotope dilution mass
      spectrometry (IDMS).
AB  - Vector models which progressively lead to a general model for isotope dilution
      mass spectrometry (IDMS) are presented for the case of two 'monitor isotopes' and
      one blend involved. They enable one to find the boundary conditions for
      performing IDMS, and cover the cases of highly enriched isotopes, radioactive
      isotopes and ratios that are given with different denominator. The models
      identify the key measurements in their simplest form as well as the conditions
      which minimise the measurement effort and in some cases the propagated
      measurement uncertainties. The equations are discussed and compared with other
      published IDMS equations. Combined with discussion on fundamental aspects of
      IDMS, this results in an even more 'general' but also more complex IDMS equation.

PMID- 14574431
TI  - Effects of intensity of repetitive acoustic stimuli on neural adaptation in the
      ventral cochlear nucleus of the rat.
AB  - To study neural adaptation as a function of stimulus intensity, auditory near
      field evoked potentials were recorded from the ventral cochlear nucleus in awake
      Long Evans rats. Responses to 250-ms trains of repetitive clicks (pulse rates
      ranging from 100 to 1000 pulses per second) were collected at stimulus
      intensities of 5, 10, 30, 50 and 70 dB SPL. The amplitude of the first negative
      (N1) component of the average evoked potentials to individual pulses in the train
      was measured by using a subtraction method. The N1 responses were normalized with
      respect to the highest cochlear nucleus potential observed in the train, and then
      plotted as a function of click position in the train. As expected, the general
      trend of the curves was an exponential decay reaching a plateau more or less
      rapidly as a function of both intensity and rate of stimulation. Fitting these
      curves with exponential decay equations revealed that the rapid time constant
      decreased for increasing stimulus intensities whereas the short-term time
      constant is relatively independent of intensity. The amount of adaptation
      (expressed as the ratio of the plateau to the first peak amplitude) was
      substantially less prominent at low intensities (5-10 dB SPL) and low rates (100
      200 pulses per second) than at higher intensities and high rates. These results
      indicate that adaptation patterns obtained in the ventral cochlear nucleus by
      using near-field evoked potentials exhibit properties comparable to those already
      present at the level of the auditory nerve.

PMID- 14574430
TI  - Corticofugal modulation of the auditory thalamus.
AB  - In the present article, we summarize the recent progress on investigating the
      mechanism of corticofugal modulation on the auditory thalamus of mammals
      excluding the bat as it has a specialized auditory system. The article comprises:
      (1) a review of the anatomy and physiology of the auditory thalamus, and a
      discussion of (2) the corticofugal modulation of the lemniscal nucleus of the
      medial geniculate body (MGB), (3) modulation of the non-lemniscal MGB, (4)
      modulation of the specific responses to acoustic signals with various parameters,
      such as the sound intensity and the onset and offset of the stimulus, and,
      finally, (5) the possible function of the corticofugal system in the auditory
      attention.

PMID- 14574433
TI  - Establishment of traceability of ammonium nitrogen determination in wastewater.
AB  - A case study is presented for the establishment of traceability for ammonium
      nitrogen determination in wastewater in a routine laboratory in order to fulfil
      the requirements of ISO/IEC standard 17025. The necessary relevant information
      was obtained from the method validation data, the quality control data and
      equipment calibration certificates. The method of measurement is described
      together with the measurement equation, selected traceable reference standards
      and the associated measurement uncertainty. The major sources of uncertainty of
      the result of measurement were identified and the combined uncertainty was
      calculated. Identification of the main uncertainty sources represents the basis
      for target operations for reducing the measurement uncertainty of this
      determination.

PMID- 14574434
TI  - Continuous-flow separation and pre-concentration coupled on-line to solid-surface
      fluorescence spectroscopy for the simultaneous determination of o-phenylphenol
      and thiabendazole.
AB  - A novel and single flow-injection system combined with solid-surface fluorescence
      detection is proposed in this work for the resolution of a mixture of two widely
      used pesticides (o-phenylphenol and thiabendazole). The continuous-flow
      methodology is based on the implementation of on-line pre-concentration and
      separation of both analytes on the surface of C18 silica gel beads placed just
      inside the flow cell, implemented with gel-phase fluorimetric multi-wavelength
      detection (using 305/358 and 250/345 nm as excitation/emission wavelengths for
      thiabendazole and o-phenylphenol, respectively). The separation of the pesticides
      was possible owing to the different retention/desorption kinetics of their
      interactions with the solid support in the zone where the stream impinges on the
      solid material. No previous separation of the analytes before they reach the flow
      cell is needed thereby simplifying substantially both the procedure and the
      manifold. By using a sample volume of 2,600 microL, the system was calibrated in
      the range 0.5-16 and 5-120 ng mL(-1) with detection limits of 0.09 and 0.60 ng
      mL(-1) for thiabendazole and o-phenylphenol, respectively. The RSD values (n=10)
      were about 1% for both analytes. The proposed methodology was applied to
      environmental water samples and also to various commercial pesticide formulations
      containing both analytes. Recovery percentages were 97-103% and 98-102% for
      thiabendazole and o-phenylphenol, respectively.

PMID- 14574435
TI  - Determination of Cr(VI) in ambient airborne particulate matter by a species
      preserving scrubber-sampling technique.
AB  - Airborne particulate matter has been sampled at a location close to a
      metallurgical plant in North-Rhine-Westphalia, Germany, and first results on the
      chromium(VI) content in the collected dust are presented. A special procedure
      using a scrubber as sampling device was used to preserve Cr(VI) during the
      sampling procedure. The scrubber solution which consisted of 0.1 mol L(-1) TRIS
      buffer solution was adjusted to a slightly alkaline pH of 8.6 to reduce the
      oxidation potential of Cr(VI) and to avoid possible oxidation of Cr(III) to
      Cr(VI), for example by oxygen (or ozone at ambient concentrations). After
      sampling Cr(VI) was pre-concentrated on an anion-exchange material and eluted
      with aqueous 0.6 mol L(-1) sodium perchlorate solution. After elution, a species
      selective complex of Cr(VI) with diphenylcarbazide (DPC) was prepared; this was
      extracted into n-hexanol and quantified by UV-visible spectrophotometry. A
      detection limit of 0.9 ng m(-3) for Cr(VI) in ambient aerosols can be achieved
      with this method.

PMID- 14574436
TI  - Dissociative electron attachment to gas-phase glycine.
AB  - By using a high-resolution electron energy monochromator low-energy electron
      attachment to gas-phase glycine (H2NCH2COOH, or G) has been studied by means of
      mass spectrometric detection of the product anions. In the same way as for
      several other biologically relevant molecules no stable parent anion was formed
      by free electron attachment. The largest dissociative electron attachment (DEA)
      cross-section, approximately 5x10(-20) m2, was observed for (G-H)-+H at an
      electron energy of 1.25 eV. Glycine and formic acid (HCOOH) have several common
      features, because a precursor ion can be characterized by electron attachment to
      the unoccupied pi* orbital of the -COOH group. At higher incident electron
      energies several smaller fragment anions are formed. Except for H-, which could
      not be observed in this study, there was good agreement with an earlier
      investigation by Gohlke et al.

PMID- 14574437
TI  - Combined biological and chemical assessment of estrogenic activities in
      wastewater treatment plant effluents.
AB  - Five wastewater treatment plant effluents were analyzed for known endocrine
      disrupters and estrogenicity. Estrogenicity was determined by using the yeast
      estrogen screen (YES) and by measuring the blood plasma vitellogenin (VTG)
      concentrations in exposed male rainbow trout (Oncorhynchus mykiss). While all
      wastewater treatment plant effluents contained measurable concentrations of
      estrogens and gave a positive response with the YES, only at two sites did the
      male fish have significantly increased VTG blood plasma concentrations after the
      exposure, compared to pre-exposure concentrations. Estrone (E1) concentrations
      ranged up to 51 ng L(-1), estradiol (E2) up to 6 ng L(-1), and ethinylestradiol
      (EE2) up to 2 ng L(-1) in the 90 samples analyzed. Alkylphenols,
      alkylphenolmonoethoxylates and alkylphenoldiethoxylates, even though found at
      microg L(-1) concentrations in effluents from wastewater treatment plants with a
      significant industrial content, did not contribute much to the overall
      estrogenicity of the samples taken due to their low relative potency. Expected
      estrogenicities were calculated from the chemical data for each sample by using
      the principle of concentration additivity and relative potencies of the various
      chemicals as determined with the yeast estrogen screen. Measured and calculated
      estradiol equivalents gave the same order of magnitude and correlated rather well
      (R(2)=0.6).

PMID- 14574438
TI  - D-amphetamine responses in catechol-O-methyltransferase (COMT) disrupted mice.
AB  - RATIONALE: We have earlier found that 1). COMT inhibitors did not enhance
      amphetamine-induced dopamine efflux into striatal extracellular, that 2). they
      did not increase dopamine levels in striatal tissue and that 3). they did not
      potentiate amphetamine-induced turning behavior of hemiparkinsonian rats.
      Further, when COMT knockout mice were challenged with l-dopa or a dopamine
      transporter (DAT) inhibitor, an accumulation of dopamine occurred and the
      neurochemical and locomotor effects of l-dopa and GBR 12909 were modified
      accordingly. OBJECTIVE: Since DAT inhibitors and amphetamine apparently have
      different mechanisms of action, we were interested to see how COMT knockout mice
      would react to d-amphetamine treatment. METHODS: We measured the effects of d
      amphetamine on locomotor activity and on the levels of catecholamines and their
      metabolites in striatal microdialysis fluid and in striatal, hypothalamic and
      cortical brain regions of COMT gene disrupted mice. Striatal dopamine receptor
      binding was also determined. RESULTS. After d-amphetamine administration, the
      DOPAC content in homozygous mice was 3-fold in the striatum, 17- to 18-fold in
      the cortex and 7- to 8-fold in the hypothalamus higher than in wild-type control
      mice, and there were no indications of genotypexsex interactions. However, the
      lack of COMT did not potentiate d-amphetamine-induced dopamine levels in brain
      tissue or in striatal extracellular fluid. D-amphetamine-induced (10 mg/kg)
      hyperlocomotion was less suppressed in male COMT knockout mice than in their wild
      type counterparts. Striatal dopamine D(1) and D(2) receptor levels in male mice
      were not altered by COMT gene disruption. CONCLUSIONS: Changes in COMT activity
      modulates dopamine metabolism but the behavioral effects of d-amphetamine in male
      mice only to a small extent, and this action does not seem to depend on the
      actual extracellular dopamine concentration. Nor is it mediated through
      compensatory changes in dopamine D(1) and D(2) receptor levels. In dopaminergic
      neurons, the contribution of intracellular COMT remains secondary in conditions
      when dopamine is released by d-amphetamine.

PMID- 14574439
TI  - Different pattern of brain c-Fos expression following re-exposure to ethanol or
      sucrose self-administration environment.
AB  - Exposure of alcohol addicts to alcohol-related environmental cues may elicit
      alcohol-seeking behavior and lead to relapse to heavy drinking. The aim of the
      present study was to identify brain regions activated by alcohol (ethanol)
      related stimuli in Wistar rats trained to lever press for 8% ethanol solution in
      operant self-administration cages. Ethanol self-administration was stabilized in
      a maintenance phase, which lasted for 30 days. c-Fos protein expression was used
      as a marker of neuronal activation.Re-exposure to ethanol self-administration
      environment after 30-day but not after 24-h abstinence increased the number of
      Fos-positive nuclei in the thalamic paraventricular nucleus, granular insular
      cortex and medial prefrontal cortex. In general, no differences were found in c
      Fos protein expression between the rats allowed to self-administer alcohol and
      the subjects exposed only to alcohol-related stimuli. In contrast, no increase in
      c-Fos immunoreactivity was observed in rats trained to lever press for sucrose
      solution and exposed to sucrose-related environmental stimuli after 30-day
      abstinence. Taken together, these results suggest that at least some thalamo
      cortical circuits become more responsive to ethanol-paired stimuli after
      prolonged abstinence and that ethanol- and sucrose-seeking behavior may be
      regulated by partially different neural mechanism(s).

PMID- 14574441
TI  - Constitutive and inducible levels of CYP1A1 and CYP1A2 in rat cerebral cortex and
      cerebellum.
AB  - We examined the constitutive and inducible levels of microsomal cytochromes P450
      1A1 and 1A2 (CYP1A) in rat cerebral cortex and cerebellum at the level of
      proteins by western blot analysis, and by catalytic activities via
      ethoxyresorufin O-deethylase (EROD) and methoxyresorufin O-demethylase (MROD). In
      the cerebral cortex, cytochrome P450 1A1 (CYP1A1) protein was more abundant than
      cytochrome P450 1A2 (CYP1A2) protein. Treatment with beta-naphthoflavone (beta
      NF) caused a slight decrease in the level of the former but induced the latter
      5.8-fold. In the cerebellum, in contrast to the cerebral cortex, CYP1A1 protein
      was less abundant than CYP1A2 protein in untreated rats, and while beta-NF
      treatment caused a 3.3-fold induction of CYP1A1 protein, it resulted in a 10-fold
      decrease in CYP1A2 protein. The CYP1A-preferential activity EROD was 2.3-fold
      higher in the cerebellum than in the cerebral cortex, and was induced 1.5-fold
      and 1.9-fold in the cerebellum and cerebral cortex, respectively, by beta-NF
      treatment. The CYP1A2-preferential activity MROD was 3-fold higher in the
      cerebellum than in the cerebral cortex, and was repressed 2.2-fold in the
      cerebellum but induced 3.7-fold in the cerebral cortex following beta-NF
      treatment. The results show that CYP1A1 and CYP1A2 proteins and catalytic
      activities are constitutively expressed in brain but are differentially inducible
      in the rat cerebral cortex and cerebellum.

PMID- 14574440
TI  - Human drug metabolising cytochrome P450 enzymes: properties and polymorphisms.
AB  - The cytochrome P450s are responsible for about 75% of phase I dependent drug
      metabolism and for the metabolism of a huge amount of dietary constituents and
      endogenous chemicals. The human has 59 active genes, and 6 of those encode
      important drug metabolising enzymes. About 40% of cytochrome P450 dependent drug
      metabolism is catalysed by polymorphic enzymes and such drug P450 interactions
      are frequently seen in adverse drug reaction reports. In this contribution an
      update of human cytochrome P450 enzymology and pharmacogenetics is given with
      particular emphasis on CYP1B1, CYP2B6, CYP2E1 and CYP3As.

PMID- 14574442
TI  - Inter-species comparisons of hepatic cytochrome P450 enzyme levels in male
      ruminants.
AB  - Our current knowledge about the biotransformation enzymes in wild ruminants is
      limited. The present study aimed to compare basic levels and specific activities
      of cytochrome P450 isoforms (CYP1A, 2A, 2B, 2C, 2D, 2E, 3A, 4A) in males of red
      deer ( Cervus elaphus), fallow deer ( Dama dama), roe deer ( Capreolus capreolus)
      and mouflon ( Ovis musimon). The proteins from the major cytochrome P450 (CYP)
      subfamilies were detected in all ruminant species by Western blotting, using
      polyclonal antibodies raised against rat or human CYP enzymes. The immunochemical
      data seem to suggest that humans and wild ruminants share some similar hepatic
      CYP enzymes corresponding to members of subfamilies 2 and 3; ruminant liver
      samples also contained two proteins cross-reacting with anti-rat CYP1A
      antibodies. High activities of CYP1A enzymes found in liver microsomes of male
      fallow deer and roe deer are indicative of increased susceptibility of these
      species towards promutagens that are metabolically activated by these CYPs. On
      the other hand, low activities of CYP1A-dependent alkoxyresorufin O-dealkylase
      activities were detected in male mouflons. Oxidative metabolism of testosterone
      was significantly higher in wild ruminants than the values previously reported
      from bulls. Androstene-3,17-dione and 6beta-hydroxytestosterone were the most
      important products of testosterone oxidation in liver microsomes of all the
      ruminant species under study. The highest CYP3A-dependent testosterone 6beta
      hydroxylase activity was found in mouflons and fallow deer. A different pattern
      of CYP activities towards testosterone was found in roe deer, which showed high
      activities of testosterone 2beta-hydroxylase and lower production of androstene
      3,17-dione. An increased activity of CYP4A-dependent laurate 12-hydroxylase found
      in roe deer and mouflons might indicate a higher metabolic turnover of fatty
      acids. The data on CYP activities indicated that high metabolic rates of
      steroids, fatty acids, and xenobiotics may occur in male wild ruminants. The
      highest hepatic activities specific for CYP3A, CYP2C, CYP2D, and CYP2E enzymes
      were found in mouflon, suggesting that this species has the highest
      biotransformation capacity.

PMID- 14574443
TI  - Glucuronidation patterns of common urinary and serum monoester phthalate
      metabolites.
AB  - Metabolism of most diesters of phthalic acid in humans occurs by an initial phase
      I biotransformation in which phthalate monoesters are formed, followed by a phase
      II biotransformation in which phthalate monoesters react with glucuronic acid to
      form their respective glucuronide conjugates. The phase II conjugation increases
      water solubility and facilitates urinary excretion of phthalate, and reduces the
      potential biological activity because the putative biologically active species is
      the monoester metabolite. In this study, we report percentages of glucuronidation
      of four common phthalate monoesters, monoethyl (mEP), monobutyl (mBP), monobenzyl
      (mBzP), and mono-2-ethylhexyl phthalate (mEHP) in a subset of urine (mEP n=262,
      mBP n=283, mBzP n=328, mEHP n=119) and serum (mEP n=93, mBP n=149, mEHP n=141)
      samples from the general US population. The percentages of free and conjugated
      monoester excreted in urine differed for the various phthalates. For the more
      lipophilic monoesters (i.e., mBP, mBzP, and mEHP), the geometric mean of free
      monoester excretion ranged from 6 to 16%. The contrary was true for the most
      hydrophilic monoester, mEP, for which about 71% was excreted in urine as its free
      monoester. Furthermore, percentages of free and conjugated monoesters were
      similar for mEP, mBP and mEHP among serum and urine samples. Serum mBzP was
      largely below the method limit of detection. Interestingly, the serum mEP and mBP
      levels were less than 3% and 47%, respectively, of their urinary levels, whereas
      the level of mEHP was similar both in urine and serum.

PMID- 14574444
TI  - Gene expression in the liver of Long-Evans cinnamon rats during the development
      of hepatitis.
AB  - The Long-Evans cinnamon (LEC) rat, an authentic model for Wilson disease, is
      characterized by a mutation in the Atp7b gene leading to a defective copper
      excretion and, as a consequence, to an accumulation of the metal in the liver and
      copper-associated hepatotoxicity. In the present communication expression
      profiles of genes in the liver from wild-type Long-Evans agouti (LEA) and LEC
      rats at different stages of copper accumulation and liver disease were
      investigated. Disease states were defined according to serum aspartate
      aminotransferase activity and bilirubin levels in serum and from histopathology
      of the liver. Gene expression was determined with the Affymetrix RTU34
      oligonucleotide array covering 1031 genes. Compared to the LEA rat, the
      nondiseased LEC rat with already increased hepatic copper level showed an
      enhanced expression of genes, particularly related to oxidative stress and DNA
      damage. During the progression of the liver disease, in particular genes related
      to oxidative stress, DNA damage, apoptosis and inflammation with acute-phase
      reaction were upregulated.

PMID- 14574445
TI  - Effects of daily stress or repeated paraoxon exposures on subacute pyridostigmine
      toxicity in rats.
AB  - Pyridostigmine (PYR) is a carbamate cholinesterase (ChE) inhibitor used during
      the Persian Gulf War as a pretreatment against possible chemical nerve agent
      attack. Because of its quaternary structure, PYR entry into the central nervous
      system is limited by the blood-brain barrier (BBB). Following reports of
      unexplained illnesses among Gulf War veterans, however, central nervous system
      effects of PYR have been postulated through either stress-induced alteration of
      BBB permeability or via interactions with other neurotoxic agents. We evaluated
      the effects of daily physical (treadmill running) stress or daily exposure to a
      subclinical dosage of the organophosphate ChE inhibitor paraoxon (PO) on ChE
      inhibition in blood, diaphragm and selected brain regions in young adult male
      Sprague-Dawley rats following subacute PYR exposures. In physical stress studies,
      rats were placed on a treadmill for 90 min each day for 14 days just prior to PYR
      (0, 3, or 10 mg/kg per day) administration. In PO-PYR interaction studies, rats
      were treated with PO (0, 0.05, or 0.1 mg/kg per day) 1 h prior to daily PYR (0 or
      3 mg/kg per day) administration for 14 consecutive days. Rats were evaluated
      daily for signs of cholinergic toxicity and were killed 1 h after the final PYR
      treatment. Forced running increased plasma corticosterone levels throughout the
      experiment (on days 1, 3, 7 and 14) when measured immediately after termination
      of stress. PYR-treated rats in the high dosage (10 mg/kg per day) group exhibited
      slight signs of toxicity (involuntary movements) for the first 6 days, after
      which tolerance developed. Interestingly, signs of cholinergic toxicity following
      PYR were slightly but significantly increased in rats forced to run on the
      treadmill prior to dosing. ChE activities in whole blood and diaphragm were
      significantly reduced 1 h after the final PYR challenge, and ChE inhibition in
      diaphragm was significantly greater in stressed rats than in non-stressed
      controls following high dose PYR (10 mg/kg per day). No significant effects of
      treadmill running on PYR-induced ChE inhibition in brain regions were noted,
      however. Repeated subclinical PO exposure had no apparent effect on functional
      signs of PYR toxicity. As with repeated treadmill running, whole blood and
      diaphragm ChE activities were significantly reduced 1 h after the final PYR
      administration, and ChE inhibition was significantly greater with combined PO and
      PYR exposures. Brain regional ChE activity was significantly inhibited after
      daily PO exposure, but no increased inhibition was noted following combined PO
      and PYR dosing. We conclude that, while some stressors may under some conditions
      affect functional signs of toxicity following repeated pyridostigmine exposures,
      these changes are likely to occur via alteration of peripheral cholinergic
      mechanisms and not through enhanced entry of pyridostigmine into the brain.

PMID- 14574446
TI  - Embryo-lethal and teratogenic effect of the new platinum compound DPR in pregnant
      mice.
AB  - Embryo-lethal and teratogenic effects caused by the cisplatin-procaine complex
      cis-diaminechloro-[2-(diethylamino) ethyl 4-amino-benzoate, N(4)]
      chlorideplatinum(II) monohydrochloride monohydrate (DPR) were examined in CD-1
      mice after a single administration of 7, 14, 21 or 28 mg/kg, injected on day 6,
      9, 13 or 16 of pregnancy. At day 18 of pregnancy fetuses were removed and
      carefully examined for external, visceral and skeletal malformations under a
      dissecting microscope. A significant reduction of maternal weight gain was
      observed in pregnant mice after the administration of 21 (day 13) or 28 mg/kg
      (days 9 and 13) DPR. The exposure to DPR during the organogenesis and early
      histogenesis periods of prenatal development (administration on day 9 or 13)
      induced a significant reduction of the mean percentage of live fetuses and a
      significant increase of the mean percentage of dead and resorbed fetuses. A dose
      dependent reduction of fetal body weight was observed in surviving specimens
      exposed to DPR on embryonic day 9, 13 or 16. The analysis of surviving fetuses
      killed on day 18 of gestation showed that a few, but statistically significant,
      external malformations and visceral anomalies were observed after administration
      of 21 or 28 mg/kg DPR on embryonic day 13. External malformations consisted of
      three hepato-omphalocele and six palatoschisis (one random palatoschisis was also
      observed at 21 mg/kg DPR given on day 9), while visceral anomalies included only
      renal pelvis dilatation. Skeletal anomalies affected fetuses independently of the
      day of treatment and were more frequent at the highest doses of DPR. They
      consisted of a delay in skull ossifications, vertebral and sternal anomalies, and
      formation of extra ribs. A low and non-significant incidence of skeletal
      malformations (asymmetric sternum) was noticed in fetuses. Our data demonstrated
      that DPR can cause embryotoxic effects if administered during the period of
      organogenesis and early histogenesis. Beside embryo-lethality, DPR induced growth
      retardation and malformations in surviving fetuses.

PMID- 14574447
TI  - Acetaldehyde adducts in the brain of alcoholics.
AB  - Acetaldehyde binds to some proteins and becomes a Schiff base. It is assumed that
      after the consumption of ethanol the acetaldehyde binds to the proteins to form
      adducts, and such acetaldehyde adducts are associated with organ diseases. We
      investigated the detection of acetaldehyde adducts in the brain region of a human
      alcoholics. Brain samples collected from an alcoholic autopsied case were used.
      Determination of acetaldehyde adducts was performed using a fluorescence
      immmunohistochemical staining method with antibodies against acetaldehyde
      adducts. We demonstrated acetaldehyde adducts in the frontal cortex and the
      midbrain of an alcoholics. Our studies showed that an acetaldehyde adduct was
      produced in the brain of alcoholics.

PMID- 14574448
TI  - Effects of chlorohydroxyfuranones on 3-methylcholanthrene-induced neoplastic
      transformation in the two-stage transformation assay in C3H 10T1/2 cells.
AB  - 3-Chloro-4-(chloromethyl)-5-hydroxy-2(5 H)-furanone (CMCF), 3-chloro-4-methyl-5
      hydroxy-2(5 H)-furanone (MCF) and 3,4-dichloro-5-hydroxy-2(5 H)-furanone (MCA)
      are chlorination byproducts in disinfected drinking water. These compounds are
      positive in genotoxicity tests in vitro. We have previously shown that 3-chloro-4
      (dichloromethyl)-5-hydroxy-2(5 H)-furanone (MX) can induce malignant transformed
      foci in the two-stage cell transformation assay in C3H 10T1/2 cells in vitro in
      both the initiation and promotion phases. In the present study we compared the
      effects of CMCF, MCF and MCA in the same assay. C3H 10T1/2 mouse embryonic
      fibroblasts were exposed to these chlorohydroxyfuranones (CHFs) at three
      different concentrations in the initiation phase or the promotion phase of the
      assay. In the latter experiments 3-methylcholanthrene (MC, 5 micro g/ml) was used
      as the initiating chemical. The phorbol ester 12- O-tetradecanoylphorbol-13
      acetate (TPA, 0.3 micro g/ml) was used as a positive control promoter. At the end
      of the assay (6 weeks from the start), the transformation foci were counted and
      scored after fixation and staining of the cells. When added at the initiation
      phase of the assay on their own, CMCF and MCF, but not MCA, increased the
      transformation foci formation. TPA added in the promotion phase did not modify
      the responses of CMCF and MCF but TPA increased the number of foci in MCA-treated
      cells. When CHFs were added during the promotion phase to the MC-initiated cells,
      MCF and MCA enhanced the development of the transformation foci. The effect of
      CMCF was equivocal since at higher concentrations CMCF actually decreased the
      number of the MC-induced foci. Including the previous data for MX in this assay
      and considering the lowest active concentrations, the initiation activity of the
      foci formation decreased in the order MX >CMCF >MCF, i.e. with the decreasing
      number of chlorine atoms of the methyl group in the 4-position of the CHF
      molecule (two, one, and zero, respectively). In contrast, the activity in the
      promotion phase did not follow the same pattern. MX, MCF and MCA were all active
      over the same concentration range. Hence, in addition to MX, MCF and MCA may also
      possess some potential to promote tumor development.

PMID- 14574449
TI  - Report of accidental CS ingestion among seven patients in central Israel and
      review of the current literature.
AB  - A report of seven people who accidentally drank a juice contaminated with CS (o
      chlorobenzylidene malononitrile) is given. Due to its mucosal irritating
      properties, CS (also known as "tear gas") is commonly used by policemen and
      soldiers in riot control. However, only a few reports of its ingestion by humans
      exist. Ingestion of CS may cause immediate irritation of the oral mucosa and
      gastrointestinal symptoms later on. Damage of internal organs, which has been
      shown in animals but only rarely in humans, is probably related to the dose
      ingested. The extensive use of CS gas merits recognition of the signs and
      symptoms of its exposure in order to reduce anxiety in both patients and medical
      staff and to facilitate fast and efficient management.

PMID- 14574450
TI  - Antioxidant effect of gamma-tocopherol supplied by propofol preparations
      (Diprivan) during ischemia-reperfusion in experimental lung transplantation.
AB  - Free radicals are involved in ischemia-reperfusion injury and inflammatory
      processes. The commercial formulation of the anesthetic propofol contains gamma
      tocopherol and delta-tocopherol, which may exert antioxidant effects during
      transplantation. Animals were randomly assigned to a control group or
      experimental groups for lung transplantation after 3 and 24 h of ischemia.
      Individual tocopherols, malondialdehyde, biochemical indices, and hemodynamic,
      blood gas, and ventilatory parameters were determined during reperfusion. Results
      showed that administration of commercially available propofol provoked a time-
      and dose-dependent increment in serum gamma-tocopherol and delta-tocopherol in
      control animals and in the group receiving lungs subjected to 3 h of ischemia,
      but not in the group with 24 h of ischemia. Malondialdehyde levels increased
      during reperfusion and did not differ significantly between the two experimental
      groups, which did not differ with respect to lung function either. gamma
      Tocopherol, supplied by the anesthetic, may act as an antioxidant that is
      consumed during reperfusion. This potential effect could be relevant to the
      choice of anesthetic agents in situations where free radical damage to tissues is
      expected.

PMID- 14574451
TI  - Nitric oxide generation mediated by beta-adrenoceptors is impaired in platelets
      from patients with Type 2 diabetes mellitus.
AB  - AIMS/HYPOTHESIS: Type 2 diabetic patients have been shown to have reduced basal
      platelet nitric oxide synthase activity, which is a possible contributor to the
      vascular complications seen in the disease. We investigated platelet nitric oxide
      generation stimulated by beta-adrenoceptors and adenylyl cyclase in Type 2
      diabetic patients and control subjects. METHODS: Platelets isolated from blood
      taken from nine Type 2 diabetic patients and nine healthy control subjects of
      similar age were treated with isoproterenol 1 micro mol/l, forskolin 1 micro
      mol/l or vehicle. Platelet nitric oxide synthase activity was measured by L
      [(3)H]-arginine to L-[(3)H]-citrulline conversion, cyclic GMP content by
      radioimmunoassay, and nitric oxide synthase type 3 expression by western
      blotting. RESULTS: Basal platelet nitric oxide synthase activity was lower in
      diabetic patients than in control subjects (0.01+/-0.02 pmol L-citrulline/10(8)
      platelets, compared with 0.12+/-0.05; p<0.05), although no corresponding
      difference was seen in basal platelet cyclic GMP (0.61+/-0.39 and 0.13+/-0.22
      pmol cyclic GMP/10(8) platelets respectively; p=0.37). In control subjects
      isoproterenol 1 micro mol/l and forskolin 1 micro mol/l increased platelet nitric
      oxide synthase activity (to 0.27+/-0.08 and 0.27+/-0.07 pmol L-citrulline/10(8)
      platelets respectively; p<0.05 for each in comparison with basal) and cyclic GMP
      (to 1.84+/-0.41 and 1.86+/-0.48; p<0.05 for each in comparison with basal). This
      effect was not achieved in diabetic patients. Isoproterenol- and forskolin
      stimulated cyclic GMP correlated inversely with plasma glucose and HbA(1c).
      Platelet nitric oxide synthase type 3 expression was not different in control and
      diabetic subjects and was not changed by acute exposure of platelets to
      isoproterenol. CONCLUSIONS/INTERPRETATION: Nitric oxide generation stimulated by
      beta-adrenoceptors and adenylyl cyclase is impaired in platelets of people with
      Type 2 diabetes mellitus, with no corresponding change in nitric oxide synthase
      type 3 expression. It is possible that this impairment contributes to the
      thrombotic and atherosclerotic complications of Type 2 diabetes.

PMID- 14574452
TI  - Quantitative trait locus analysis of fungal disease resistance factors on a
      molecular map of grapevine.
AB  - A full-sibling F1 population comprising 153 individuals from the cross of
      'Regent' x 'Lemberger' was employed to construct a genetic map based on 429
      molecular markers. The newly-bred red grapevine variety 'Regent' has multiple
      field-resistance to fungal diseases inherited as polygenic traits, while
      'Lemberger' is a traditional fungus-susceptible cultivar. The progeny segregate
      quantitatively for resistances to Plasmopara viticola and Uncinula necator,
      fungal pathogens that threaten viticulture in temperate areas. A double pseudo
      testcross strategy was employed to construct the two parental maps under high
      statistical stringency for linkage to obtain a robust marker frame for subsequent
      quantitative trait locus (QTL) analysis. In total, 185 amplified fragment length
      polymorphism, 137 random amplified polymorphic DNA, 85 single sequence repeat and
      22 sequence characterized amplified region or cleaved amplified polymorphic
      sequence markers were mapped. The maps were aligned by co-dominant or doubly
      heterozygous dominant anchor markers. Twelve pairs of homologous linkage groups
      could be integrated into consensus linkage groups. Resistance phenotypes and
      segregating characteristics were scored as quantitative traits in three or four
      growing seasons. Interval mapping reproducibly localized genetic factors that
      correlated with fungal disease resistances to specific regions on three linkage
      groups of the maternal 'Regent' map. A QTL for resistance to Uncinula necator was
      identified on linkage group 16, and QTLs for endurance to Plasmopara viticola on
      linkage groups 9 and 10 of 'Regent'. Additional QTLs for the onset of berry
      ripening ("veraison"), berry size and axillary shoot growth were identified.
      Berry color segregated as a simple trait in this cross of two red varieties and
      was mapped as a morphological marker. Six markers derived from functional genes
      could be localized. This dissection of polygenic fungus disease resistance in
      grapevine allows the development of marker-assisted selection for breeding, the
      characterization of genetic resources and the isolation of the corresponding
      genes.

PMID- 14574453
TI  - Expression of epitope-tagged LMW glutenin subunits in the starchy endosperm of
      transgenic wheat and their incorporation into glutenin polymers.
AB  - The low-molecular-weight (LMW) glutenin subunits are components of the highly
      cross-linked glutenin polymers that confer viscoelastic properties to gluten and
      dough. They have both quantitative and qualitative effects on dough quality that
      may relate to differences in their ability to form the inter-chain disulphide
      bonds that stabilise the polymers. In order to determine the relationship between
      dough quality and the amounts and properties of the LMW subunits, we have
      transformed the pasta wheat cultivars Svevo and Ofanto with three genes encoding
      proteins, which differ in their numbers or positions of cysteine residues. The
      transgenes were delivered under control of the high-molecular-weight (HMW)
      subunit 1Dx5 gene promoter and terminator regions, and the encoded proteins were
      C-terminally tagged by the introduction of the c-myc epitope. Stable
      transformants were obtained with both cultivars, and the use of a specific
      antibody to the c-myc epitope tag allowed the transgene products to be readily
      detected in the complex mixture of LMW subunits. A range of transgene expression
      levels was observed. The addition of the epitope tag did not compromise the
      correct folding of the trangenic subunits and their incorporation into the
      glutenin polymers. Our results demonstrate that the ability to specifically
      epitope-tag LMW glutenin transgenes can greatly assist in the elucidation of
      their individual contributions to the functionality of the complex gluten system.

PMID- 14574454
TI  - A RAPD, AFLP and SSR linkage map, and QTL analysis in European beech (Fagus
      sylvatica L.).
AB  - The genetic linkage map of European beech ( Fagus sylvatica L.) that we report
      here is the first to our knowledge. Based on a total of 312 markers (28 RAPDs,
      274 AFLPs, 10 SSRs) scored in 143 individuals from a F(1) full-sib family. Two
      maps (one for each parent) were constructed according to a "two-way pseudo
      testcross" mapping strategy. In the male map 119 markers could be clustered in 11
      major groups (971 cM), while in the female map 132 markers were distributed in 12
      major linkage groups (844 cM). In addition, four and one minor linkage groups
      (doublets and triplets) were obtained for the male and female map respectively.
      The two maps cover about 82% and 78% of the genome. Based on the position of 15
      AFLP and 2 SSR loci segregating in both parents, seven homologous linkage groups
      could be identified. In the same pedigree we investigated the association with
      genetic markers of several quantitative traits: leaf area, leaf number and shape
      in 2 different years, specific leaf area, leaf carbon-isotope discrimination and
      tree height. A composite interval-mapping approach was used to estimate the
      number of QTLs, the amount of variation explained by each of them, and their
      position on the genetic linkage maps. Eight QTLs associated with leaf traits were
      found that explained between 15% and 35% of the trait variation, five on the
      female map and three on the male map.

PMID- 14574456
TI  - A novel transfecting peptide comprising a tetrameric nuclear localization
      sequence.
AB  - The transport of exogenous DNA into the nucleus of eukaryotic cells is a
      prerequisite for successful gene delivery. To favor nuclear transport we
      synthesized a tetramer of the nuclear localization signal (NLS) of the SV40 large
      T-antigen as a novel nonviral gene delivery vector. This 4.4-kDa lysine-rich
      peptide (NLSV404) binds and compacts DNA by electrostatic interaction and forms
      stable polyplexes. Apart from its sequence-specific potency to mediate nuclear
      accumulation of conjugated albumin, NLSV404 also displays properties of nuclear
      transport for plasmid DNA as confirmed by fluorescence in situ hybridization.
      Further, NLSV404 polyplexes are shown to efficiently transfect various cell lines
      such as 16HBE14o-, HeLa S6, and Cos7 cells. NLSV404 polyplexes displayed at least
      20-fold higher transfection rates than analogous polyplexes formed by the nuclear
      transport-deficient mutant sequence cNLS. Using growth-arrested cells, NLSV404
      complexes were at least 100-fold more efficient than cNLS complexes. Combination
      of NLSV404 peptide but not of cNLS peptide with preformed polyethylenimine and
      dendrimer DNA complexes resulted in a strong increase in transfection efficiency.
      Incubation of cells prior to transfection with NLSV404 polyplexes with excess
      free peptide NLSV404 but not with cNLS resulted in a dose-dependent dramatic
      decrease in the transfection rate, suggesting a sequence-specific competitive
      inhibition. These results indicate that NLSV404 mediates nuclear accumulation of
      transfected plasmid DNA and that it can be a highly useful component of nonviral
      gene vectors.

PMID- 14574455
TI  - Evidence for genetic epistasis in human insulin resistance: the combined effect
      of PC-1 (K121Q) and PPARgamma2 (P12A) polymorphisms.
AB  - Insulin resistance is believed to be under the control of several genes often
      interacting each other. However, whether genetic epistasis does in fact modulate
      human insulin sensitivity is unknown. In 338 healthy unrelated subjects from
      Sicily, all nondiabetic and not morbidly obese, we investigated whether two gene
      polymorphisms previously associated with insulin resistance (namely PC-1 K121Q
      and PPARgamma2 P12A) affect insulin sensitivity by interacting. PC-1 X121Q
      subjects showed higher level of fasting glucose, lower insulin sensitivity (by
      both the Matsuda insulin sensitivity index and M values at clamp, the latter
      performed in a subgroup of 113 subjects representative of the overall cohort) and
      higher insulin levels during the oral glucose tolerance test (OGTT) than PC-1
      K121K subjects. In contrast, no difference in any of the measured variables was
      observed between PPARgamma2 P12P and X12A individuals. The deleterious effect of
      the PC-1 X121Q genotype on each of these three variables was significant and
      entirely dependent upon the coexistence of the PPARgamma2 P12P genotype. Among
      PPARgamma2 P12P carriers also fasting insulin and glucose levels during OGTT were
      higher in PC-1 X121Q than in K121K individuals. In contrast, no deleterious
      effect of the PC-1 X121Q genotype was observed among PPARgamma2 X12A carriers;
      rather, in these subjects a lower body mass index and consequently lower fasting
      insulin level was observed in PC-1 X121Q than in K121K carriers. Overall, a
      significant interaction between the two genes was observed on body mass index,
      insulin levels (both fasting and after OGTT) and both insulin sensitivity (i.e.,
      insulin sensitivity index and M value) and insulin secretion (i.e., HOMA-B%)
      indexes.

PMID- 14574457
TI  - Amifostine induces anaerobic metabolism and hypoxia-inducible factor 1 alpha.
AB  - PURPOSE: The cytoprotective mechanism of amifostine (WR-2721) implies free
      radical scavenging and DNA repair activities. We investigated additional
      cytoprotective pathways involving intracellular hypoxia and the activation of the
      hypoxia-inducible factor (HIF) pathway, a key transcription factor regulating
      glycolysis, angiogenesis and apoptosis, which is also linked with
      radioresistance. MATERIALS AND METHODS: The glucose and oxygen levels in the
      peripheral blood of patients receiving 1000 mg amifostine were determined at
      various time-points in order to investigate the metabolic changes induced by
      amifostine. MDA468 breast tumor cell lines were incubated with a high amifostine
      concentration (10 m M) to overcome the natural resistance of cancer cells to
      influx of the non-hydrolyzed WR-2721, and the HIF1 alpha protein levels were
      determined by Western blot analysis. In vivo experiments with Wistar rats were
      performed in order to assess immunohistochemically changes in the intracellular
      accumulation of HIF1 alpha induced by amifostine (200 mg/kg). RESULTS: By 30 min
      following amifostine administration, the hemoglobin oxygen saturation and pO(2)
      levels had increased in the peripheral blood while glucose levels had reduced,
      providing evidence that normal tissue metabolism switches to glycolytic pathways.
      Incubation of cell lines with amifostine resulted in HIF1 alpha induction. In
      Wistar rats administration of amifostine resulted in increased HIF1 alpha
      accumulation in normal tissues. CONCLUSIONS: Since it is doubtful whether
      dephosphorylation of amifostine to the active metabolite WR-1065 occurs within
      tumoral tissues (an acidic environment that lacks vascular alkaline phosphatase
      activity), intracellular hypoxia and upregulation of HIF1 alpha represents an
      additional, normal tissue-specific, amifostine cytoprotective pathway.

PMID- 14574458
TI  - Metabolism of a cholesterol-rich microemulsion (LDE) in patients with multiple
      myeloma and a preliminary clinical study of LDE as a drug vehicle for the
      treatment of the disease.
AB  - PURPOSE: Previously we have shown that cholesterol-rich microemulsions that bind
      to LDL receptors have the ability to concentrate in acute myeloid leukemia cells
      and in ovarian and breast carcinomas. Thus, LDE may be used as a vehicle for
      drugs directed against neoplastic cells. Indeed, we subsequently showed that when
      carmustine is associated with LDE the toxicity of the drug is significantly
      reduced in patients with advanced cancers. The aim of the present study was to
      verify whether LDE may be taken up by multiple myeloma cells and whether patients
      with multiple myeloma respond to treatment with LDE associated with carmustine.
      METHODS: A total of 131 consecutive volunteer patients with recently diagnosed
      multiple myeloma classified as clinical stage IIIA had their plasma lipid profile
      determined. LDE plasma kinetics were performed in 14 of them. Cell uptake of LDE
      and the cytotoxicity of carmustine associated with the emulsion were evaluated in
      a multiple myeloma cell line. A pharmacokinetic study of LDE-carmustine was
      performed in three patients. Finally, an exploratory clinical study of LDE
      carmustine (carmustine dose 180 mg/m(2) body surface every 4 weeks) was performed
      in seven untreated multiple myeloma patients. RESULTS: LDL cholesterol was lower
      in the 131 multiple myeloma patients than in healthy controls and the fractional
      clearance rate (FCR, in units per minute) in the 14 multiple myeloma patients was
      twice that in 14 paired healthy control subjects. Moreover, entry of LDE into
      multiple myeloma cells was shown to be mediated by LDL receptors. Taken together,
      these findings indicate that LDE may target multiple myeloma. The exploratory
      clinical study showed that gammaglobulin decreased by 10-70% (mean 36%) after
      three cycles and by 25-75% (mean 44%) after six cycles. Furthermore, there was
      amelioration of symptoms in all patients. Cholesterol concentrations increased
      after treatment, suggesting that the treatment resulted in at least partial
      destruction of neoplastic cells with receptor upregulation. Side effects of the
      treatment were negligible. CONCLUSIONS: Because it targets multiple myeloma and,
      when associated with an antineoplastic agent, produces therapeutic responses in
      patients with fewer side effects, LDE has the potential for use as a drug vehicle
      in the treatment of the disease.

PMID- 14574459
TI  - Pharmacokinetics of etoposide in cancer patients treated with high-dose etoposide
      and with dexrazoxane (ICRF-187) as a rescue agent.
AB  - PURPOSE: The pharmacokinetics of etoposide were studied in cancer patients with
      brain metastases treated with high-dose etoposide in order to determine if the
      pharmacokinetics were altered by the use of dexrazoxane as a rescue agent to
      reduce the extracerebral toxicity of etoposide. METHODS: Etoposide plasma levels
      were determined by HPLC. RESULTS: The etoposide pharmacokinetics described by a
      monophasic first-order elimination model were found to be similar to other
      reported data in other settings and at similar doses. CONCLUSIONS: The
      pharmacokinetics of etoposide were unaffected by dexrazoxane rescue.

PMID- 14574460
TI  - Effects of RSR13 and oxygen on the cytotoxicity of cisplatin and carboplatin to
      EMT6 mouse mammary tumor cells in vitro and in vivo.
AB  - PURPOSE: RSR13, 2-[4-[2-[(3,5-dimethylphenyl)amino]-2-oxoethyl]phenoxy]-2
      methylpropanoic acid monosodium salt, allosterically modifies hemoglobin to
      increase tumor pO(2), increases the effect of radiation in animal tumor models,
      and is in phase III clinical trials as an adjuvant to radiotherapy. Cisplatin and
      carboplatin, two commonly used anticancer drugs have been used in combination
      with radiotherapy. Some studies have suggested that the cytotoxic effects of
      these drugs are altered in hypoxia. This study tested whether RSR13 plus oxygen
      breathing increased the cytotoxicity of cisplatin and carboplatin in vivo.
      METHODS: Solid EMT6 tumors in BALB/c Rw mice were treated with cisplatin (5-30
      microg/g) or carboplatin (5-200 microg/g) along with 150 microg/g RSR13 in
      combination with oxygen breathing. Tumor cell survival was assayed using
      clonogenic assays. The effects of pre- and posttreatments with RSR13 and oxygen
      breathing on the cytotoxicity of cisplatin or carboplatin were also examined. To
      assess whether RSR13 had direct effects on the cytotoxicity of the drugs,
      exponentially growing monolayers of EMT6 mouse mammary carcinoma cells were
      treated with graded concentrations of cisplatin or carboplatin for 2 h along with
      simultaneous (2 h) RSR13 treatments or with prolonged (22 h) pre- or
      posttreatment incubations with 100 microM RSR13. RESULTS: Single or multiple
      treatments with 150 microg/g RSR13 plus oxygen breathing had no effect on the
      viability of cells in EMT6 tumors in mice. After treatment with cisplatin or
      carboplatin, the tumor cell survival tended to be lower in oxygen-breathing mice
      especially at higher doses of cisplatin. Treatment with RSR13 plus oxygen
      breathing beginning 15 min before administration of the alkylating agents did not
      alter the cytotoxicity of cisplatin or carboplatin from that seen with oxygen
      breathing alone. Pretreatment with RSR13 plus oxygen at 22 and 14 h prior to
      administration of either cisplatin or carboplatin did not alter the effect of
      either alkylating agent. Treatment with RSR13 plus oxygen breathing beginning 15
      min before administration of the alkylating agents and lasting for 2 or 5 h did
      not alter the cytotoxicity of either drug from that seen with oxygen breathing
      alone. The cytotoxicity of cisplatin was not altered by treatment with oxygen
      alone or with RSR13 plus oxygen for 5 h after cisplatin injection. For
      carboplatin, treatment with oxygen alone and with RSR13 plus oxygen for 5 h after
      injection increased to similar extents the response of the tumor cells compared
      to that seen with assays at 2 h. Neither short simultaneous treatments, prolonged
      pretreatment incubations, nor prolonged posttreatment incubations with RSR13
      altered the survival of EMT6 cells in cultures treated with cisplatin or
      carboplatin. CONCLUSIONS: These findings indicate that RSR13 in combination with
      oxygen breathing does not alter the cytotoxicity of cisplatin or carboplatin when
      used simultaneously, as a pretreatment or as a posttreatment in vitro or in vivo.
      Our in vivo findings indicate trends that support previous findings that
      cisplatin is more cytotoxic to well-oxygenated tumor cells than to hypoxic tumor
      cells, and that this effect can be improved by improving tumor oxygenation, but
      the differences seen in our studies did not achieve statistical significance.

PMID- 14574461
TI  - Successful treatment by selective arterial embolization of severe retroperitoneal
      hemorrhage secondary to bone marrow biopsy in post-polycythemic myelofibrosis.
AB  - Severe retroperitoneal hemorrhage represents an infrequent and serious
      complication of bone marrow biopsy. A 53-year-old man, diagnosed with
      polycythemia vera 12 years earlier, was submitted to a bone marrow biopsy due to
      the appearance of anemia with clinical and hematological features suggesting
      myelofibrotic transformation, a diagnosis that was confirmed by the marrow study.
      At 2 h of a right anterior iliac bone marrow trephine biopsy, the patient
      suddenly developed severe pain in the area of the biopsy, with antialgic flexion
      of the right leg. Computed tomographic (CT) scan of the abdomen showed a 5 x 9.5
      cm hematoma in the right iliac and psoas muscles. The patient was initially
      managed with analgesics and transfusional support, but the pain persisted and a
      continuous fall in the hematocrit was observed in the following days.
      Angiographic examination of the right external iliac artery showed contrast
      extravasation arising from the circumflex iliac branch, which was embolized using
      polivinyl alcohol particles and one coil. Following such procedure, the patient
      recovered uneventfully and was discharged in good condition a few days later.
      This case illustrates the effectiveness of an endovascular approach in providing
      a fast and minimally invasive treatment for this life-threatening complication of
      bone marrow trephine biopsy.

PMID- 14574462
TI  - RNA interference (RNAi) in hematology.
AB  - RNA interference (RNAi), an evolutionary highly conserved process of post
      transcriptional gene silencing, can be triggered by small interfering RNAs
      (siRNAs) that mediate sequence-specific mRNA degradation. Since the first reports
      in 1998, RNAi has rapidly been developed into an effective tool to specifically
      knock down gene expression in a wide variety of target cells. Accordingly, RNAi
      is currently used for both systematic functional genomics in several organisms
      and for specific therapeutic intervention in preclinical models of different
      diseases characterized by aberrant gene expression. However, since siRNAs are not
      replicated in mammalian cells during the process of RNAi, kinetic aspects of RNAi
      induced gene silencing that eventually depend on the intracellular level of siRNA
      must be considered for each analytical or therapeutic application in these cells.
      We summarize here some aspects of siRNA design and delivery, of RNAi kinetics,
      potential side effects, and limitations of siRNA-mediated gene silencing, as well
      as putative RNAi targets for functional and/or therapeutic intervention in
      hematopoietic cells.

PMID- 14574463
TI  - Anatomical study of the variations in innervation of the orbicularis oculi by the
      facial nerve.
AB  - While the divisions of the facial nerve in the face are well known, the
      innervation of the orbicularis oculi by the different distal branches of the
      facial nerve is poorly described. To determine which branches of the facial nerve
      play a role in this innervation, the facial nerve was dissected in 30 fresh
      cadavers. The innervation of this muscle was in the form of two plexuses, a
      superior one, most often (93%) formed by the union of the temporal and superior
      zygomatic branches, and an inferior one, usually formed (63%) by the union of the
      inferior zygomatic and superior buccal branches. This new mode of innervation
      explains how, without damage to both plexuses, innervation of orbicularis oculi
      by the facial nerve remains functional. It also explains the often unsatisfactory
      results of treatment of primary blepharospasm, and the unusual character of
      palsies of this muscle in cervicofacial lifts.

PMID- 14574464
TI  - The interdomal fat pad of the nose: a new anatomical structure.
AB  - The nose is one of the most operated organs in the body and its anatomy has been
      well defined by plastic and ENT surgeons. Although rhinoplasty is the most
      commonly performed operation in plastic surgery, some unexpected results and
      complications may be related to unknown or unclarified anatomical structures in
      the nose. We aimed to evaluate the interdomal region in four fresh cadavers and
      24 patients who underwent open rhinoplasty, since the nasal tip area is the most
      difficult part of the rhinoplasty. Detailed cartilage and soft tissue
      interactions were studied in fresh cadavers. The existence of the interdomal fat
      pad as a separate anatomical structure was proven in necropsy specimens from
      cadavers using various histochemical dyes. Nasal tip ultrasonography was
      performed preoperatively in patients who underwent rhinoplasty. All patients had
      a fat pad in the interdomal space, of varying sizes, but fatty (bulbous) noses
      had larger fat pads. Interdomal fat pad tissue, which occupies the interdomal
      space, was demonstrated by ultrasonography. The size of the fat pads varied from
      1.2 mm x 2.4 mm to 3.6 mm x 5.2 mm. Anatomical observation and biopsies were
      performed during surgery. Finally, surgical and radiological anatomy of the
      interdomal fat pad was demonstrated in all cadavers and patients. We speculate
      that the interdomal fat pad is an important anatomical structure and may
      contribute to unexpected postoperative results in rhinoplasty. This newly defined
      fat pad can be assessed by ultrasonography, a safe and inexpensive technique. The
      surgical approach to the interdomal fat pad is solely through open rhinoplasty
      technique. Thus, a consideration of the interdomal fat pad and detection of its
      size preoperatively may play a key role in choice of technique and success of
      rhinoplasty.

PMID- 14574465
TI  - Spatial relationships between masticatory muscles and their innervating nerves in
      man with special reference to the medial pterygoid muscle and its accessory
      muscle bundle.
AB  - The relationships between the positional arrangement of the surrounding and
      innervating nerves of the muscles supplied by the mandibular nerve, in particular
      those medial to the main trunk of the nerve, were examined in 24 head halves from
      12 Japanese cadavers by dissection from the inside after removal of the bony
      elements except for the mandible. In ten sides of five heads, the lingual nerve
      pierced the medial pterygoid muscle, and the bundle lateral to the nerve was
      found to be separated as an accessory muscle bundle. The accessory bundle was
      frequently attached to the mylohyoid muscle. In addition, the inferior alveolar
      nerve and the lingual nerve frequently communicated, and in four specimens a
      branch from the lingual nerve entered the mylohyoid to communicate with the
      proper nerve. The innervation pattern indicated that the medial pterygoid muscle
      consists of the anteromedial and the posterolateral main parts, and sometimes has
      an accessory bundle. Based on the present findings and the previous studies of
      the positional relationships between the muscles and nerves by our research
      group, we propose that the muscles innervated by the mandibular nerve could be
      classified as an inner group (the lateral pterygoid) and an outer group (the
      other muscles). A possible scheme of the positional relationships between the
      muscles and nerves is presented.

PMID- 14574466
TI  - Coracoclavicular joints. Reflections upon incidence, pathophysiology and etiology
      of the different forms.
AB  - Since the first description of the coracoclavicular joint in 1861, many papers
      have been published reporting its occurrence, anatomical description, and
      geographical distribution. However, there are as yet no published articles with a
      convincing explanation for the rather variable forms of this variant. In this
      study, we investigated the occurrence of the coracoclavicular joint in the
      current and medieval population of Toulouse city and propose, through biometric
      measures, an explanation for the different forms of this anatomical variant. A
      total of 2192 chest X-rays taken for various conditions at a receiving hospital
      and 392 specimens (784 scapulae and an equal number of clavicles) of the L'Isle
      Jourdain Series were examined with this aim. When present in the osteologic
      collection, the sizes of the articular conoid process as well as the height of
      the corresponding coracoid and acromial processes were noted. A coracoclavicular
      joint was noted in 0.82% and in 1.78% of the individuals examined in the
      radiological and osteologic series, respectively. The conoid process varied in
      size and correlated with the disposition of each correspondent coracoacromial
      arch. Osteoarthritis was noted in some of these joints when there was discordance
      between the conoid process size and the architecture of the correspondent
      coracoacromial arch, suggesting impingement. Our findings support a genetic
      origin for this variant, and suggest that its occurrence is also probably
      influenced by environmental factors. Osteoarthritis of this joint may be
      responsible for shoulder pain.

PMID- 14574468
TI  - Visualization of the temporal bone of the Chinese Visible Human.
AB  - Temporal bone anatomy is very difficult to understand. After dataset acquisition
      of the first Chinese Visible Human, we processed the two-dimensional images to
      build a digitized visible model of the temporal bone and explore the role of
      virtual endoscopy in the inner ear. On a SGI workstation three-dimensional
      computer reconstructions of the ear were generated from the Chinese visible human
      dataset, viewing the middle and inner ear imitating the traditional otoscopy. The
      three-dimensional data of the temporal bone were then converted to STL format,
      and the temporal bone replica were fabricated with rapid prototyping by laminated
      object manufacturing. The virtual model of the ear was successfully completed,
      and the virtual endoscopy improved three-dimensional visualization of the middle
      and inner ear. Physical replica of the temporal bone were built with paper; the
      accuracy was +/-0.2 mm. The reconstructed model and the replica of the temporal
      bone can be used to make preoperative plans in the complicated otoneurosurgical
      operations, allowing various surgical exercises to be carried out on the three
      dimensional stereophysical model. The virtual endoscopy stands as a promising new
      visualization technique for elucidation of the middle and inner ear and reveals a
      tremendous potential in both clinical and educational settings, providing
      morphological data for the image diagnosis and otoneurosurgery.

PMID- 14574467
TI  - The normal menisci: in vivo MRI measurements.
AB  - The aim of this study was to determine dimensions of the normal menisci in 174
      healthy subjects by using MRI. The menisci were divided into three zones
      (anterior horn, mid-body, posterior horn). The height and width of the both
      menisci were measured. For the medial meniscus; the height and width of the
      anterior horn were 5.32 mm and 7.78 mm, the height and width of the mid-body were
      5.03 mm and 7.37 mm, and the height and width of the posterior horn were 5.53 mm
      and 11.71 mm, respectively. For the lateral meniscus, the height and width of the
      anterior horn were 4.33 mm and 8.88 mm, the height and width of the mid-body were
      4.94 mm and 8.37 mm, and the height and width of the posterior horn were 5.36 mm
      and 9.70 mm, respectively. Three cases (1.7%) of discoid lateral meniscus were
      encountered. The results of this study should help to establish standard
      measurements, and to differentiate between normal and pathologic conditions of
      the menisci of the knee joint.

PMID- 14574480
TI  - Evacuation of hydatid liver cysts using a laparoscopic trocar.

PMID- 14574481
TI  - Experience with laparoscopic medial and lateral dissection of the rectosigmoid
      for cancer.

PMID- 14574482
TI  - Role of preoperative transcatheter arterial chemoembolization for resectable
      hepatocellular carcinoma: relation between postoperative course and the pattern
      of tumor recurrence.
AB  - The effects of preoperative transcatheter arterial chemoembolization (TACE) were
      retrospectively evaluated in patients with resectable hepatocellular carcinoma
      (HCC). A total of 227 patients who underwent hepatectomy for HCC were studied
      (146 underwent preoperative TACE and 81 did not). We compared operative outcome,
      mortality, and disease-free survival between TACE and non-TACE groups. We also
      compared the pattern of recurrence and postrecurrence survival between subgroups
      according to staging. Of the 227 patients, 105 with tumor stage I-II were
      assigned to group A (group A/TACE, n = 69; group A/non-TACE, n = 36), and the
      remaining 122 with tumor stage III-IV were assigned to group B (group B/TACE, n
      =77; group B/non-TACE, n =45). Complete necrosis was found to be more frequent in
      the TACE group ( p < 0.01). Operating time, blood loss, and mortality did not
      differ between those who did and did not undergo preoperative TACE. TACE did not
      significantly improve disease-free survival within either the entire TACE group
      or group A/TACE. In contrast, in group B/TACE the disease-free survival rates
      were significantly higher than in group B/non-TACE. Furthermore, both
      extrahepatic metastasis and diffuse intrahepatic metastasis were significantly
      more frequent in group B/non-TACE than in group B/TACE. The preoperative TACE
      also improved the postrecurrence survival in group B. We speculate that
      preoperative TACE reduced tumor recurrence and that it might confer a survival
      advantage after surgery, particularly in patients with advanced HCC. In addition,
      it is expected that this procedure may improve the pattern of tumor recurrence
      when it does occur.

PMID- 14574484
TI  - High dose intravenous immunoglobulin g pretreatment: effect on lipid peroxidation
      and reperfusion injury to the liver.
AB  - The aim of this study was to examine the effect of intravenous immunoglobulin G
      (IVIG) compared with that of gadolinium chloride (GdCl3) in the inhibition of
      Kupffer cell activation on lipid peroxidation after severe total hepatic
      ischemia/reperfusion (I/R). Male Wistar rats ( n = 40) were randomly divided into
      four equal groups: a sham-operation group, a control I/R group, and two I/R
      groups pretreated with either IVIG or GdCl3 intravenously. Following 60 minutes
      of total hepatic ischemia and 120 minutes of reperfusion, the rats were
      sacrificed and liver and blood samples collected. Additional animals ( n = 80)
      were followed up for survival rate determination. Results showed that I/R
      decreased the survival rate to 10%, increased the levels of aspartate (AST) and
      alanine (ALT) transaminase and lactate dehydrogenase (LDH) in serum to 2487,
      2189, and 4236 IU/L, respectively, and increased malondialdehyde (MDA) levels in
      liver to 1.552 nmol/g compared with 1.114 nmol/g in the sham operation group.
      Pretreatment with GdCl3 increased the survival rate to 50% and decreased the
      levels of AST, ALT, and LDH in serum to 1496, 1298, and 3245 IU/l, respectively.
      Pretreatment with IVIG increased the survival rate to 60% and decreased the
      levels of AST, ALT, and LDH in serum to 449, 367, and 1456 IU/l, respectively,
      and the levels of MDA in liver to 1.153 and 1.148 nmol/g for GdCl3 and IVIG
      respectively. Histologic examination showed protection of liver parenchyma in the
      animals treated with GdCl3 or IVIG.

PMID- 14574485
TI  - Subareolar subcutaneous injection of blue dye versus peritumoral injection of
      technetium-labeled human albumin to identify sentinel lymph nodes in breast
      cancer patients.
AB  - Lymphatic mapping in breast cancer patients is a widely used technique for
      axillary staging, though the optimal technique is not yet established. The
      purpose of this study was to show that subareolar and subcutaneous injection of
      blue dye drains to the same sentinel lymph node (SLN) in the axillary basin as
      does peritumoral injection of technetium (Tc)-labeled albumin. Two injection
      methods were compared in 154 consecutive patients with newly diagnosed pT1 or pT2
      breast cancers (tumor size 5-45 mm). The diagnosis of invasive breast cancer was
      confirmed by core needle biopsy. Peritumoral injection of 40 to 60 MBq 99Tc
      labeled colloidal albumin was performed 18 to 20 hours prior to surgery. In
      addition, 2 ml of blue dye was injected subcutaneously into the subareolar plexus
      of the same patients exactly 5 minutes prior to incision and dissection of the
      SLNs. The blue and hot SLNs were identified by searching for the blue lymphatic
      vessel and the blue lymph node and by counting the radioactivity with a gamma
      probe. The correlation between the blue nodes and the hot nodes was examined.
      Altogether, 154 patients were enrolled in the study. Three patients had bilateral
      breast cancer, and a total of 157 sentinel lymph node biopsies (SLNBs) were
      performed. The SLNs could be identified in 155 of the 157 SLNBs (98.7%), and the
      hot node clearly corresponded to the blue node in 151 of the 155 SLNBs (97.4%).
      Neither a hot node nor a blue node could be identified in 2 of the 157 SLNBs
      (1.3%). No concordance between the blue node and the hot node could be achieved
      in 4 of the 155 SLNBs (2.6%). Injection of blue dye into the subareolar lymphatic
      plexus shows excellent correlation with peritumoral injection of technetium
      labeled albumin concerning the identification of SLNs. Our results support the
      hypothesis that the lymphatic drainage of the breast parenchyma and the
      subareolar plexus leads to the same sentinel lymph node. It is a rapid, reliable
      method for identifying SLNs in breast cancer patients. It is easy to perform,
      especially in nonpalpable tumors, and it does not disturb surgery by discoloring
      peritumoral tissue.

PMID- 14574487
TI  - Paul of Aegina: landmark in surgical progress.

PMID- 14574489
TI  - Acute respiratory distress syndrome in the septic surgical patient.
AB  - The acute respiratory distress syndrome (ARDS) is a process of acute inflammatory
      lung injury that affects a diverse array of surgical and medical patients. The
      syndrome is mediated by a complex and interacting system of chemical mediators
      produced by several types of pulmonary cells. Regardless of the predisposing
      causes, activation of the nuclear factor kappa B seems to be, at the molecular
      level, a signature event of ARDS, leading to the rapid activation of
      intracellular signaling pathways, which coordinate the induction of multiple
      genes encoding inflammatory mediators. There are at least two compelling reasons
      for promoting an understanding of these interactions and their molecular
      mediators and second messengers: new therapies intended to modulate these factors
      continue to be developed, and the levels of some of these molecules, most notably
      cytokines, may serve as early indicators of the onset of ARDS.

PMID- 14574491
TI  - Pancreatic autotransplantation in chronic pancreatitis.
AB  - The apancreatic state secondary to resective surgery for chronic pancreatitis is
      associated with a high rate of late morbidity and mortality that is due, in part,
      to endocrine insufficiency. Resective procedures should, therefore, be used very
      selectively. Over the last 2 decades we have seen a shift from extensive distal
      resections to limited proximal resections. This is because of the lowering of the
      operative mortality of pancreatic head resection and its better results in pain
      relief, while preserving in situ the body and tail of the gland with its
      metabolic functions. Islet autotransplantation and segmental pancreatic
      autotransplantation were introduced in 1977 and 1978, respectively. Over 150 and
      25 cases of these operations have been reported, respectively. Both techniques
      are evolving with a goal to improve results. Procedures placing the graft in the
      iliac fossa and anastomosing the pancreatic duct to the jejunum are now favored
      over groin placement and duct occlusion. Islet autotransplants achieve a higher
      yield of islet cells and decrease the exocrine impurity of the preparation. Both
      methods can prevent or delay the onset of diabetes mellitus, and when diabetes
      mellitus does occur, it is frequently easier to manage. The long-term function of
      the grafts appears to be dependent on the beta-cell mass available in the
      diseased pancreas, the loss of cells related to the transplant procedure, and the
      characteristics of gradual loss of function from the type of transplant used.
      Although extensive pancreatic resections are occasionally required, the
      possibility of autotransplantation should be considered in those patients.

PMID- 14574490
TI  - Pathogenesis of pain in chronic pancreatitis: ongoing enigma.
AB  - The pathogenesis of pain in chronic pancreatitis remains an enigma. The cause of
      pain is almost certainly multifactorial and may vary at different stages of the
      disease process. These factors may include the release of excessive oxygen
      derived free radicals, tissue hypoxia and acidosis, inflammatory infiltration
      with influx of pain transmittent substances into damaged nerve ends, and the
      development of pancreatic ductal and tissue fluid hypertension due to
      morphological changes of the pancreas. Investigations into the causes of pain
      have been limited by changes in the dynamics with the progression of the disease
      process, limitations in studying functional and morphological changes of the
      pancreas in the clinical setting, and the psychosomatic profile of patients. Many
      of these patients are addicted to alcohol, and suffer from personality disorders.
      The difficulty in quantifying pain, which is at best subjective, further
      compounds the issue, especially when assessing the efficacy of treatment.

PMID- 14574492
TI  - In vitro biological activities of transmembrane superantigen staphylococcal
      enterotoxin A fusion protein.
AB  - The bacterial superantigen staphylococcal enterotoxin A (SEA) stimulates T cells
      bearing certain TCR Vbeta domains when binding to MHC II molecules, and is a
      potent inducer of CTL activity and cytokine production. Antibody-targeted SEA
      such as C215 Fab-SEA and C242 Fab-SEA has been investigated for cancer therapy in
      recent years. We have previously reported significant tumor inhibition and
      prolonged survival time in tumor-bearing mice treated with a combination of both
      C215Fab-SEA and Ad IL-18 (Wang et al., Gene Therapy 8:542-550, 2001). In order to
      develop SEA as an universal biological preparation in cancer therapy, we first
      cloned a SEA gene from S. aureus (ATCC 13565) and a transmembrane (TM) sequence
      from a c- erb-b2 gene derived from human ovarian cancer cell line HO-8910, then
      generated a TM-SEA fusion gene by using the splice overlap extension method, and
      constructed the recombinant expression vector pET-28a-TM-SEA. Fusion protein TM
      SEA was expressed in E. coli BL21(DE3)pLysS and purified by using the histidine
      tag in this vector. Purified TM-SEA spontaneously associated with cell membranes
      as detected by flow cytometry. TM-SEA stimulated the proliferation of both human
      PBLs and splenocytes derived from C57BL/6 (H-2b) mice in vitro. This study thus
      demonstrated a novel strategy for anchoring superantigen SEA onto the surfaces of
      tumor cells without any genetic manipulation.

PMID- 14574511
TI  - The value of scintigraphy in the evaluation of oropharyngeal dysphagia.
AB  - Healthy adults can swallow boluses of 20 ml water in a single swallow.
      Individuals with impaired swallowing, however, may be unable to do so, instead
      requiring two or more swallows; this phenomenon is called "piecemeal
      deglutition". The term "dysphagia limit" refers to the volume at which piecemeal
      deglutition occurs. The aim of our study was to investigate the potential value
      of scintigraphic evaluation of piecemeal deglutition and dysphagia limit in
      patients with dysphagia, based on correlation with the results of submental
      electromyography (SM-EMG) and laryngeal sensor monitoring (LS). The study
      population comprised 24 patients with dysphagia secondary to neurological
      disorders and ten normal adults, who formed a control group. In the scintigraphic
      evaluation, subjects underwent four separate dynamic studies using 5, 10, 15 and
      20 ml of water containing 0.5 mCi technetium-99m labelled sulphur colloid, and
      time-activity curves (TACs) were created for each study. Static thoracic images
      were also recorded in order to detect airway aspiration Observation of two or
      more peaks on TACs within the 10-s acquisition period was considered a sign of
      piecemeal deglutition. If piecemeal deglutition occurred at or below 20 ml, this
      volume was regarded as the dysphagia limit. Piecemeal deglutition was not found
      in any normal subjects; by contrast, it was observed in 14 of the 24 (58%)
      patients on scintigraphy and in 17 (71%) patients on EMG and LS. In three
      patients, signs of the airway aspiration were observed on static thoracic images.
      Scintigraphic and electrophysiological findings were in agreement in 19 patients
      (79%), and the correlation between scintigraphy and the electrophysiological
      methods for the evaluation of dysphagia was statistically significant (r=0.57,
      P=0.003). The novel finding of this study is the demonstration of piecemeal
      deglutition and dysphagia limit on scintigraphic studies in patients with
      neurogenic dysphagia. Based on this finding we consider that scintigraphic
      evaluations of piecemeal deglutition and dysphagia limit could be of value
      especially in centres which do not have electrophysiological test facilities. The
      technique should be added to the list of standard scintigraphic methods for the
      evaluation of patients with oropharyngeal dysphagia.

PMID- 14574512
TI  - Attenuation compensation in cerebral 3D PET: effect of the attenuation map on
      absolute and relative quantitation.
AB  - It is generally well accepted that transmission (TX)-based non-uniform
      attenuation correction can supply more accurate absolute quantification; however,
      whether it provides additional benefits in routine clinical diagnosis based on
      qualitative interpretation of 3D brain positron emission tomography (PET) images
      is still the subject of debate. The aim of this study was to compare the effect
      of the two major classes of method for determining the attenuation map, i.e.
      uniform versus non-uniform, using clinical studies based on qualitative
      assessment as well as absolute and relative quantitative volume of interest-based
      analysis. We investigated the effect of six different methods for determining the
      patient-specific attenuation map. The first method, referred to as the uniform
      fit-ellipse method (UFEM), approximates the outline of the head by an ellipse
      assuming a constant linear attenuation factor (mu=0.096 cm(-1)) for soft tissue.
      The second, referred to as the automated contour detection method (ACDM),
      estimates the outline of the head from the emission sinogram. Attenuation of the
      skull is accounted for by assuming a constant uniform skull thickness (0.45 cm)
      within the estimated shape and the correct micro value (0.151 cm(-1)) is used.
      The usual measured transmission method using caesium-137 single-photon sources
      was used without (MTM) and with segmentation of the TX data (STM). These
      techniques were finally compared with the segmented magnetic resonance imaging
      method (SMM) and an implementation of the inferring attenuation distributions
      method (IADM) based on the digital Zubal head atlas. Several image quality
      parameters were compared, including absolute and relative quantification indexes,
      and the correlation between them was checked. The qualitative evaluation showed
      no significant differences between the different attenuation correction
      techniques as assessed by expert physicians, with the exception of ACDM, which
      generated artefacts in the upper edges of the head. The mean squared error
      between the different attenuation maps was also larger when using this latter
      method owing to the fact that the current implementation of the method
      significantly overestimated the head contours on the external slices. Correlation
      between the mean regional cerebral glucose metabolism (rCGM) values obtained with
      the various attenuation correction methods and those obtained with the gold
      standard (MTM) was good, except in the case of ACDM (R(2)=0.54). The STM and SMM
      methods showed the best correlation (R(2)=0.90) and the regression lines agreed
      well with the line of identity. Relative differences in mean rCGM values were in
      general less than 8%. Nevertheless, ANOVA results showed statistically
      significant differences between the different methods for some regions of the
      brain. It is concluded that the attenuation map influences both absolute and
      relative quantitation in cerebral 3D PET. Transmission-less attenuation
      correction results in a reduced radiation dose and makes a dramatic difference in
      acquisition time, allowing increased patient throughput.

PMID- 14574513
TI  - 11C-acetate PET imaging of lung cancer: comparison with 18F-FDG PET and 99mTc
      MIBI SPET.
AB  - Recently carbon-11 acetate (AC) positron emission tomography (PET) has been
      reported to be of clinical value for the diagnosis of cancer that is negative on
      fluorine-18 fluorodeoxyglucoce (FDG) PET. We investigated the uptake of AC in
      lung cancer to determine whether this tracer is of potential value for tumour
      detection and characterisation, and to compare AC PET imaging with FDG PET and
      technetium-99m sestamibi (MIBI) single-photon emission tomography (SPET). Twenty
      three patients with 25 lung cancers underwent AC and FDG PET. Twenty of 23
      patients were also investigated with MIBI SPET. Dynamic images were acquired for
      26 min after the injection of 555 MBq of AC. Standardised uptake values (SUVs)
      and/or tumour to non-tumour activity ratios (T/N) for each tumour were
      investigated at 10-20 min after AC administration, 40-60 min after administration
      of 185 MBq FDG and 15-45 min after administration of 555 MBq MIBI. Twenty lung
      cancers were resected surgically, and the degree of tracer uptake in the primary
      lesion was correlated with histopathological features (cell dedifferentiation and
      aggressiveness) and prognosis. Rapid uptake of AC followed by extremely slow
      clearance was observed. For the purpose of tumour identification, AC PET was
      inferior to FDG PET in 8 of 25 (32%) lung cancers, and the T/N of AC was lower
      than that of FDG. However, AC PET was superior to FDG PET in the identification
      of a slow-growing tumour (bronchiolo-alveolar carcinoma). There was a positive
      correlation between AC uptake (T/N) and MIBI uptake (T/N) (r=0.799, P<0.0001). A
      positive correlation was not observed between either AC or MIBI uptake and the
      degree of cell dedifferentiation in lung adenocarcinomas, whereas FDG uptake did
      correlate with the degree of cell dedifferentiation. In lung adenocarcinoma,
      there was a weak correlation between aggressiveness and FDG uptake, but no
      correlation was evident for AC and MIBI. In addition, a positive correlation was
      not observed between AC or MIBI uptake and postoperative recurrence in lung
      adenocarcinoma, whereas FDG uptake did correlate with postoperative recurrence.
      Thus, the greater the FDG uptake, the higher the malignant grade. In conclusion,
      for the purpose of tumour identification, AC PET was inferior to FDG PET but
      superior to MIBI SPET. Neither AC nor MIBI uptake reflects the malignant grade in
      lung adenocarcinoma, whereas FDG uptake does. AC PET is less diagnostically
      informative than FDG PET in patients with lung cancer. However, AC PET may play a
      complementary role in the identification of low-grade malignancies that are not
      FDG avid.

PMID- 14574514
TI  - Early therapy monitoring with FDG-PET in aggressive non-Hodgkin's lymphoma and
      Hodgkin's lymphoma.
AB  - This study was designed to determine the value of 2-[fluorine-18]-fluoro-2-deoxy-
      d-glucose positron emission tomography (FDG-PET) in the early assessment of
      therapy response in lymphoma patients. We studied 20 patients with pathologically
      proven lymphoma, including 17 patients with aggressive non-Hodgkin's lymphoma and
      three patients with Hodgkin's lymphoma. All patients underwent whole-body FDG-PET
      imaging at baseline and after 1-2 cycles of chemotherapy. PET images were
      analysed visually and quantitatively by calculating the standardised uptake value
      (SUV). In each patient, we measured the SUV of the tumour demonstrating the
      highest FDG uptake at baseline study and the SUV of the same tumour after 1-2
      cycles of therapy. The achievement of complete response was assessed on the basis
      of a combination of clinical findings and the results of conventional imaging
      modalities. Follow-up of progression-free survival (PFS) was obtained for the
      validation of PET data. Of the 20 patients, ten achieved complete remission at
      the completion of chemotherapy and the other ten did not respond to chemotherapy.
      Of the ten responders, four are still in remission (PFS 24-34 months) while the
      other six have relapsed (PFS 8-16 months). For the prediction of 24-month
      clinical outcome, visual analysis of PET after 1-2 cycles showed high sensitivity
      (87.5%) and accuracy (80%) but low specificity (50%). Comparison with the
      baseline SUVs revealed that the responders showed a significantly greater percent
      reduction in SUV after 1-2 cycles of therapy as compared with the non-responders
      (81.2%+/-9.5% vs 35.0%+/-20.2%, P<0.001). In addition, using 60% reduction as a
      cut-off value, the responders were clearly separated from the non-responders,
      with the exception of one non-responder. In conclusion, when performed early
      during chemotherapy, FDG-PET may be predictive of clinical outcome and allows
      differentiation of responders from non-responders in cases of aggressive
      lymphoma.

PMID- 14574515
TI  - Characterization of basal hepatic bile flow and the effects of intravenous
      cholecystokinin on the liver, sphincter, and gallbladder in patients with
      sphincter of Oddi spasm.
AB  - The major objectives of this project were to establish the pattern of basal
      hepatic bile flow and the effects of intravenous administration of
      cholecystokinin on the liver, sphincter of Oddi, and gallbladder, and to identify
      reliable parameters for the diagnosis of sphincter of Oddi spasm (SOS). Eight
      women with clinically suspected sphincter of Oddi spasm (SOS group), ten control
      subjects (control group), and ten patients who had recently received an opioid
      (opioid group) were selected for quantitative cholescintigraphy with
      cholecystokinin. Each patient was studied with 111-185 MBq (3-5 mCi) technetium
      99m mebrofenin after 6-8 h of fasting. Hepatic phase images were obtained for 60
      min, followed by gallbladder phase images for 30 min. During the gallbladder
      phase, 10 ng/kg octapeptide of cholecystokinin (CCK-8) was infused over 3 min
      through an infusion pump. Hepatic extraction fraction, excretion half-time, basal
      hepatic bile flow into the gallbladder, gallbladder ejection fraction, and post
      CCK-8 paradoxical filling (>30% of basal counts) were identified. Seven of the
      patients with SOS were treated with antispasmodics (calcium channel blockers),
      and one underwent endoscopic sphincterotomy. Mean (+/-SD) hepatic bile entry into
      the gallbladder (versus GI tract) was widely variable: it was lower in SOS
      patients (32%+/-31%) than in controls (61%+/-36%) and the opioid group (61%+/
      25%), but the difference was not statistically significant. Hepatic extraction
      fraction, excretion half-time, and pattern of bile flow through both intrahepatic
      and extrahepatic ducts were normal in all three groups. Gallbladder mean ejection
      fraction was 9%+/-4% in the opioid group; this was significantly lower (P<0.0001)
      than the values in the control group (54%+/-18%) and the SOS group (48%+/-29%).
      Almost all of the bile emptied from the gallbladder refluxed into intrahepatic
      ducts; it reentered the gallbladder after cessation of CCK-8 infusion
      (paradoxical gallbladder filling) in all eight patients with SOS, but in none of
      the patients in the other two groups. Mean paradoxical filling was 204% (+/-193%)
      in the SOS group and less than 5% (P<0.05) in both the control and the opioid
      group. After treatment, six of the SOS patients had complete pain relief and one,
      partial pain relief. The basal tonus of the sphincter is variable in patients
      with SOS, and allows relatively more of the hepatic bile to enter the GI tract
      than the gallbladder. Due to simultaneous contraction of the sphincter and
      gallbladder in response to CCK-8, most of the bile emptied from the gallbladder
      refluxes into intrahepatic ducts, and reenters the gallbladder immediately after
      cessation of hormone infusion. The characteristic features of gallbladder
      filling, emptying, and paradoxical refilling with cholecystokinin provide
      objective parameters for noninvasive diagnosis of SOS by quantitative
      cholescintigraphy.

PMID- 14574517
TI  - Ultrasound of intrinsic wrist ligament and triangular fibrocartilage injuries.
AB  - OBJECTIVE: The objective of this study was to evaluate ultrasound as a diagnostic
      tool for investigating scapholunate and lunatotriquetral ligamentous and
      triangular fibrocartilage (TFC) tears. Ultrasound findings were compared to
      conventional arthrogram findings, as the reference gold standard. DESIGN AND
      PATIENTS: In total 26 patients, 17 males and 9 females ranging in age from 17 to
      35 (mean age, 34), were evaluated on referral for investigation of wrist pain.
      All patients were examined by high resolution ultrasound, using a 9-13 MHz
      transducer. All wrist ultrasound examinations were also compared to conventional
      tricompartmental arthrography, as the diagnostic gold standard reference.
      RESULTS: All ten scapholunate tears confirmed on arthrography were detected on
      ultrasound. Two of 8 lunatotriquetral and 7 of 11 TFC tears were correctly
      diagnosed on ultrasound. Sensitivity of ultrasound diagnosis ranged from 25% for
      lunatotriquetral tears to 100% for scapholunate tears. No false positive results
      were recorded for any of the three examined structures. CONCLUSION: The study
      results suggest that sonography is accurate for scapholunate tears, but is not
      accurate for evaluation of lunate-triquetral tears. It has intermediate accuracy
      for triangular fibrocartilage tears.

PMID- 14574516
TI  - Nuclear medicine imaging for the assessment of primary and recurrent head and
      neck carcinoma using routinely available tracers.
AB  - This article reviews the literature on the use of fluorine-18 fluorodeoxyglucose
      positron emission tomography (FDG PET) and thallium-201, technetium-99m sestamibi
      and technetium-99m tetrofosmin single-photon emission tomography (SPET) for the
      diagnosis and staging of primary and recurrent squamous cell carcinoma of the
      head and neck (SCCHN). A search of the MEDLINE and CancerLit databases covering
      articles entered between 1989 and February 2003 was performed. In the case of FDG
      PET, only full-ring PET studies that included comparison with conventional
      morphological imaging were considered. Due to the wide variation in methodology,
      a straightforward meta-analysis of FDG PET literature was impossible. Instead,
      indicative summary receiver-operating curves of FDG PET and morphological imaging
      techniques were generated and a paired comparison of the sensitivities and
      specificities of FDG PET and morphological imaging performed. Compared with
      conventional morphological imaging, FDG PET proved as sensitive and specific for
      the detection of primary SCCHN but more sensitive and specific for the detection
      of cervical lymph node involvement (CLNI) and recurrence of SCCHN. Additional
      studies addressing the role of FDG PET in screening for distant metastases and
      synchronous primary tumours are mandatory. Following negative conventional
      evaluations, FDG PET identifies occult primary tumours in 20-50% of patients
      presenting with CLNI. As regards the use of 201Tl, 99mTc-sestamibi and 99mTc
      tetrofosmin, more studies are required to define whether these imaging agents
      could form part of the current diagnostic armamentarium in SCCHN patients. It is
      concluded that FDG PET either is superior to or offers added value when compared
      with conventional morphological imaging techniques for the purpose of diagnosis
      and staging of primary and recurrent SCCHN.

PMID- 14574518
TI  - Upper thoracic-spine disc degeneration in patients with cervical pain.
AB  - OBJECTIVE: To study the relationship of upper thoracic spine degenerative disc
      contour changes on MR imaging in patients with neck pain. The relation between
      upper thoracic and cervical spine degenerative disc disease is not well
      established. DESIGN AND PATIENTS: One hundred and fifty-six patients referred
      with cervical pain were studied. There were 73 women and 77 men with a mean age
      of 48.6 +/- 14.6 years (range, 19 to 83 years). All MR studies were performed
      with a large 23-cm FOV covering at least from the body of T4 to the clivus. Discs
      were coded as normal, protrusion/bulge or extrusion. RESULTS: Degenerative
      thoracic disc contour changes were observed in 13.4% of patients with cervical
      pain. T2-3 was the most commonly affected level of the upper thoracic spine, with
      15 bulge/protrusions and one extrusion. Upper degenerative thoracic disc contour
      changes presented in older patients than the cervical levels (Student-Newman
      Keuls test, P < 0.001). Degenerative disc contour changes at the C7-T1, T1-2, T2
      3 and T3-4 levels were significantly correlated ( P = 0.001), but unrelated to
      any other disc disease, patient's gender or age. Degenerative cervical disc
      disease was closely related together ( P < 0.001), but not with any thoracic
      disc. CONCLUSION: A statistically significant relation was found within the upper
      thoracic discs, reflecting common pathoanatomical changes. The absence of
      relation to cervical segments is probably due to differences in their
      pathomechanisms.

PMID- 14574519
TI  - Molecular characterization of major histocompatibility complex class 1 (MHC-I)
      from squirrel monkeys (Saimiri sciureus).
AB  - Little is known about the major histocompatibility complex (MHC) class 1 in
      squirrel monkeys ( Saimiri sciureus). We cloned, sequenced and characterized two
      alleles and the cDNA of the coding region of MHC class 1 in these New World
      monkeys. Phylogenetic analyses showed that these sequences are related to HLA
      class 1 genes ( HLA-A and HLA-G). The structure and organization of one of the
      two identified clones was similar to that of a class 1 MHC gene ( HLA-A2). All
      the exon/intron splice acceptor/donor sites are conserved and their locations
      correspond to the HLA-A2 gene. The sequences of the newly described cDNAs reveal
      that they code for the characteristic class 1 MHC proteins, with all the features
      thought necessary for cell surface expression. Typical sequences for the leader
      peptide, alpha(1), alpha(2), alpha(3), transmembrane and cytoplasmic domains were
      found.

PMID- 14574520
TI  - Splicing defect in RFXANK results in a moderate combined immunodeficiency and
      long-duration clinical course.
AB  - MHC class II deficiency provokes a severe immunodeficiency characterized by a
      lack of antigen-specific immune response. In the absence of bone marrow
      transplantation (the only curative treatment), patients affected by this genetic
      recessive disease die in early childhood. However, others and we have recently
      described cases of mild or asymptomatic immunodeficiencies with defects in either
      CIITA (class II transactivator) or RFX5, both proteins required for the
      transcription of HLA-D genes. We describe in this report the first case of
      moderate immunodeficiency resulting from a defect in RFXANK, another
      transcription factor essential for HLA-D expression. The patient did not display
      any detectable expression of MHC class II molecules on B lymphocytes, monocytes
      or activated T lymphocytes. Accordingly HLA-D transcription was altered in the
      corresponding B-lymphoblastoid cell line. The defect in RFXANK was observed both
      at the transcript and protein level. Indeed a homozygous IVS4+5G>A mutation was
      evidenced in RFXANK, and shown to hamper the splicing of intron 4. However, we
      had shown previously that a defect in intron 4 can lead to the skipping of exon
      4, and that the resulting truncated protein retains the capacity to activate HLA
      DR expression. Therefore, like the two cases of moderate immunodeficiencies
      described previously, we demonstrate that the RFXANK defect presented here is
      coherent with a residual activity of the mutant protein. We thus propose that the
      common feature displayed by mildly immunodeficient patients is the leakiness of
      the mutations, which might allow a local or temporal expression of MHC class II
      molecules.

PMID- 14574521
TI  - The hydration dynamics of polyelectrolyte gels with applications to cell motility
      and drug delivery.
AB  - We combine the physics of gels with the hydrodynamics of two-phase fluids to
      construct a set of equations that describe the hydration dynamics of
      polyelectrolyte gels. We use the model to address three problems. First, we
      express the effective diffusion constants for neutral and charged spherically
      distributed gels in terms of microscopic parameters. Second, we use the model to
      describe the locomotion of nematode sperm cells. Finally, we describe the
      swelling dynamics of polyelectrolyte gels used for drug release.

PMID- 14574522
TI  - KcsA closed and open: modelling and simulation studies.
AB  - Bacterial homologues of mammalian potassium channels provide structures of two
      states of a gated K channel. Thus, the crystal structure of KcsA represents a
      closed state whilst that of MthK represents an open state. Using homology
      modelling and molecular dynamics simulations we have built a model of the
      transmembrane domain of KcsA in an open state and have compared its
      conformational stability with that of the same domain of KcsA in a closed state.
      Approximate Born energy calculations of monovalent cations within the two KcsA
      channel states suggest that the intracellular hydrophobic gate in the closed
      state provides a barrier of height approximately 5 kT to ion permeation, whilst
      in the open state the barrier is absent. Simulations (10 ns duration) in an
      octane slab (a simple membrane mimetic) suggest that closed- and open-state
      models are of comparable conformational stability, both exhibiting conformational
      drifts of approximately 3.3 A Calpha RMSD relative to the respective starting
      models. Substantial conformational fluctuations are observed in the intracellular
      gate region during both simulations (closed state and open state). In the
      simulation of open-state KcsA, rapid ( < 5 ns) exit of all three K+ ions occurs
      through the intracellular mouth of the channel. Helix kink and swivel motion is
      observed at the molecular hinge formed by residue G99 of the M2 helix. This
      motion is more substantial for the open- than for the closed-state model of the
      channel.

PMID- 14574523
TI  - Effect of external stresses on protein conformation: a computer modelling study.
AB  - The increasing use of digital technologies such as mobile phones has led to major
      health concerns about the effects of non-ionizing pulsed radiation exposure. We
      believe that the health implications of exposure to radiation cannot be fully
      understood without establishing the molecular mechanisms of biological effects of
      pulsed microwaves. We aim to establish methods for studying the molecular
      mechanisms of protein structural and energetic changes occurring due to external
      stresses related to non-ionizing radiation by using a combination of experimental
      and theoretical approaches. In this paper, we present the results from our fully
      atomistic simulation study of chemical and thermal stress response of a prototype
      protein, insulin. We performed a series of molecular dynamics simulations of
      insulin in solution under equilibrium conditions, under chemical stress (imitated
      by reducing the disulfide bonds in the protein molecule), and under short-lived
      thermal stress (imitated by increasing simulation temperature for up to 2 ns).
      The resultant protein conformational behaviour was analysed for various
      properties with the aim of establishing analysis routines for classification of
      protein unfolding pathways and associated molecular mechanisms.

PMID- 14574524
TI  - Fluorescence spectroscopic detection of mitochondrial flavoprotein redox
      oscillations and transient reduction of the NADPH oxidase-associated flavoprotein
      in leukocytes.
AB  - Steady-state and time-resolved fluorescence spectroscopy and fluorescence
      microscopy of leukocyte flavoproteins have been performed. Both living human
      peripheral blood monocytes and neutrophils have been utilized as experimental
      models, as the former relies much more heavily on mitochondrial metabolism for
      energy production than the latter. We confirm previous studies indicating that
      cellular flavoproteins absorb at 460 nm and emit at 530 nm, very similar to that
      of the FAD moiety. Furthermore, the emission properties of intracellular
      flavoproteins were altered by the metabolic inhibitors rotenone, antimycin A,
      azide, cyanide, DNP (2,4-dinitrophenol), and FCCP [carbonyl cyanide p
      (trifluoromethoxy)phenylhydrazone]. Kinetic studies revealed flavoprotein
      emission oscillations in both monocytes and neutrophils. The flavoprotein
      intensity oscillations correlated with the physiological status of the cell and
      the nature of membrane receptor ligation. Microscopy revealed the presence of
      flavoprotein fluorescence in association with the plasma membrane, intracellular
      granules and distributed throughout the cytoplasm, presumably within
      mitochondria. Metabolic inhibitors such as cyanide suggest that the plasma
      membrane and granular components are cyanide-insensitive and therefore are likely
      associated with the flavoprotein component of the NADPH oxidase, which is located
      in these two compartments. This interpretation was found to be consistent with
      structural localization of the NADPH oxidase using an antibody molecule specific
      for this protein. Using peripheral blood neutrophils, which display less active
      mitochondria, and time-resolved emission spectroscopy, we show that the NADPH
      oxidase-associated flavoprotein undergoes a periodic transient reduction of about
      54+/-2 ms in living cells. This finding is consistent with prior studies
      indicating that propagating substrate (NADPH) waves periodically promote electron
      transport across the NADPH oxidase.

PMID- 14574525
TI  - The voltage-dependent anion channel as a biological transistor: theoretical
      considerations.
AB  - The voltage-dependent anion channel (VDAC) is a porin of the mitochondrial outer
      membrane with a bell-shaped permeability-voltage characteristic. This porin
      restricts the flow of negatively charged metabolites at certain non-zero
      voltages, and thus might regulate their flux across the mitochondrial outer
      membrane. Here, we have developed a mathematical model illustrating the
      possibility of interaction between two steady-state fluxes of negatively charged
      metabolites circulating across the VDAC in a membrane. The fluxes interact by
      contributing to generation of the membrane electrical potential with subsequent
      closure of the VDAC. The model predicts that the VDAC might function as a single
      molecule biological transistor and amplifier, because according to the obtained
      calculations a small change in the flux of one pair of different negatively
      charged metabolites causes a significant modulation of a more powerful flux of
      another pair of negatively charged metabolites circulating across the same
      membrane with the VDAC. Such transistor-like behavior of the VDAC in the
      mitochondrial outer membrane might be an important principle of the cell energy
      metabolism regulation under some physiological conditions.

PMID- 14574526
TI  - An aufwuchs chamber slide for high-resolution confocal laser scanning microscopy
      and stereo imaging of microbial communities in natural biofilms.
AB  - Aufwuchs chamber slides were constructed by attaching a silicone rubber gasket to
      a glass slide with epoxy cement. For biofilm growth, the slides were suspended in
      Cayuga Lake near Ithaca, NY, for 27 days. Biofilms in the chamber were stained
      with 0.05% acridine orange. After rinsing, the chamber was filled with molten 1%
      agarose to stabilize filaments and delicate polymer structures at the biofilm
      surface. Areas of biofilm approximately 0.5 mm thick on the inner face of the
      wall of the chamber were selected for side-on optical sectioning in a confocal
      laser scanning microscope (CLSM). Stacks of high-resolution optical images
      captured by the CLSM z-sectioning software, were used to create left-right stereo
      image pairs. At low magnification the stereo pairs showed 3-D details of the
      microbial landscape in the mature biofilms. Channels, pores, and other structural
      features of the biofilm matrix were observed in peripheral regions. Higher
      magnification images revealed the 3-D distribution of specific biofilm components
      such as filaments of sheathed bacteria projecting outward into the liquid milieu,
      and organic coatings, including bacterial cells on the surfaces of mineral
      particles.

PMID- 14574527
TI  - Acute acalculous cholecystitis owing to salmonella sepsis.

PMID- 14574528
TI  - Angiotensin II involvement in adaptive enteric oxalate excretion in rats with
      chronic renal failure induced by hyperoxaluria.
AB  - Enteric secretion of oxalate is induced in rats that have chronic renal failure
      produced by 5/6 nephrectomy. The purpose of the present study was to examine
      renal and intestinal handling of oxalate in rats with chronic renal failure (CRF)
      induced by chronic hyperoxaluria. A rat model for chronic renal failure, induced
      by chronic hyperoxaluria (CH-CRF), was produced by unilateral nephrectomy
      combined with dietary ethylene glycol for 4 weeks. Both intact and unilateral
      nephrectomized rats (UN) without the oxalate load served as controls. Renal
      handling of oxalate was assessed by measurement of renal clearance of oxalate and
      creatinine while colonic handling of oxalate and chloride was determined by in
      vitro transepithelial flux measurements. Angiotensin II mediation was assessed by
      sensitivity of the transport processes to the AT(1) receptor antagonist losartan.
      Renal and colonic handling of oxalate in UN rats were similar to intact controls.
      The CH-CRF rats were hyperoxalemic, hyperoxaluric, and exhibited a twofold
      increase in oxalate clearance despite a 50% drop in creatinine clearance. Distal
      (but not proximal) colonic handling of oxalate in CH-CRF rats was reversed from
      net oxalate absorption seen in UN and intact controls to net secretion that was
      sensitive to losartan in vitro. CONCLUSION: Although enteric oxalate secretion
      can be correlated with elevations in plasma oxalate in the absence of overt renal
      insufficiency by an ANG II-independent mechanism, the present results suggest
      that some degree of renal insufficiency is necessary to induce ANG II-mediated
      colonic oxalate secretion.

PMID- 14574529
TI  - A stone farm: development of a method for simultaneous production of multiple
      calcium oxalate stones in vitro.
AB  - We have previously shown how individual calcium oxalate stones of about 1 cm can
      be grown in vitro. While this proved a design concept, it was severely limited as
      an experimental tool because of the time required to undertake comparative
      studies. Here we describe a development of this system in which six parallel
      pairs of stone generators are supplied with feed solutions generating a medium
      that is supersaturated with calcium oxalate. Twelve stones were grown
      simultaneously in aseptically prepared artificial urine over a period of 32 days
      from 100 mg to about 250 mg. Flow rates, pH and [Ca(2+)] were stable and
      reproducible over the course of the experiment. Sodium azide (0.02%) was included
      in the growth medium of six stones and caused a modest decrease in growth rate
      from 5.5 to 3.4 mg/day. The experimental design is such that this was readily
      detectable both visually and statistically ( p<0.001). This multiple stone
      growing system ("a stone farm") shows improved consistency and illustrates the
      statistical power of the technique. Azide has only a minor effect on the growth
      kinetics and can be used as an antibacterial agent in studies involving urinary
      macromolecules. The technique is suitable for practical and meaningful
      investigation of calcium oxalate stone formation in vitro.

PMID- 14574531
TI  - Dose-dependent effect of phthalate ester on testicular descent in pre-and post
      natal rats.
AB  - Mono-n-butyl phthalate (MBP) was administered to pregnant rats from the 15th to
      the 17th gestational day to investigate the dose-dependent effect of phthalate
      ester on testicular descent in both pre- and postnatal rats. Thirty pregnant rats
      (280-330 g) were separated into five groups and administered 1.0 g/kg/day MBP in
      group I, 0.5 g/kg/day in group II, 0.25 g/kg/day in group III, 0.125 g/kg/day in
      group IV from the day 15 to 17 of gestation. The rats in group V were only
      administered solvent and acted as controls. The position of the testis was
      evaluated in both pre- and postnatal rats. This was significantly higher in 20
      day old fetuses in groups I and II than in groups III, IV or V. After birth, the
      incidence of undescended testis was also higher in groups I and II compared with
      those of groups III, IV or V. The undescended testes were located in the
      abdominal cavity in groups I and II, whereas they were located at the inguinal
      region in group III. The lowest dose that induced an adverse effect on testicular
      descent was 0.25 g/kg/day. In conclusion, maternal MBP inhibited testicular
      descent in prenatal rats and thus dose-dependently induced undescended testes
      postnatally. High-doses of MBP are thus considered to inhibit the transabdominal
      descent of the testis, probably due to its estrogenic activity, whereas low-doses
      of MBP may act as an anti-androgen and thereby inhibit inguinoscrotal testicular
      descent in postnatal rats.

PMID- 14574532
TI  - Urine and serum free IGF-1 levels in patients with bladder cancer: a brief
      report.
AB  - Insulin-like growth factor (IGF)-1, a mitogenic and anti-apoptotic peptide, can
      affect the proliferation of epithelial cells, and is thought to play a role in
      cancer development. The free IGF-1 represents the biologically active fraction of
      IGF-1. We hypothesised that there is a difference in free IGF-1 levels in the
      urine and serum from patients with TCC and normal subjects. Urine and blood
      samples were collected from 30 cases of superficial TCC and an equal number
      control subjects without malignancy. Free IGF-1 levels were measured in duplicate
      by radioimmunoassay. Specimens of bladder carcinoma were staged
      histopathologically using the Mostoffi grading system. Statistical analyses were
      performed using the Mann-Whitney U-test, Pearson correlation and covariate
      analysis. There was no significant difference in urine and serum free IGF-1
      levels between the two groups. The correlation between urine and serum free IGF-1
      levels and age was not significant. There was also no significant relationship
      between free IGF-1 levels and histopathological grading. The results of this
      pilot study reveal that the free IGF-1 level does not help predict tumour marker
      in the patients with bladder cancer.

PMID- 14574533
TI  - NF-kappaB-dependent gene expression of proinflammatory cytokines in T24 cells:
      possible role in interstitial cystitis.
AB  - Our previous report of predominant activation of nuclear transcription factor NF
      kappaB in the bladder urothelium of interstitial cystitis (IC) patients suggests
      a potential role for this nuclear factor in the pathogenesis of the disease.
      Although NF-kappaB has been implicated in the pathogenesis of several
      inflammatory diseases, the downstream mechanism(s) by which it can mediate its
      effects are still fragmentary. In this study, we examined the role of this
      nuclear factor on the induction of proinflammatory cytokine gene expression in
      human bladder carcinoma T24 cells and further examined their corresponding
      protein levels in the urine of IC patients. T24 cells transduced with a dominant
      negative super-repressor IkappaB mutant (pAxCAmIkappaB-M) or wild-type adenoviral
      vectors in the presence or absence of rhTNF-alpha. Transduction efficiency and
      ability of pAxCAmIkappaB-M to inhibit NF-kappaB activation were monitored by in
      situ reporter beta-galactosidase and gel mobility shift assays, respectively.
      Expression profile analysis of proinflammatory cytokines was measured in cells
      and urine of IC patients using RT-PCR and ELISA, respectively. The activation of
      NF-kappaB by rhTNF-alpha was associated with 27, eight, ten and sevenfold
      increases in the TNF-alpha, IL-1beta, IL-6 and IL-8 transcripts, respectively. In
      contrast, abrogation of the TNF-alpha-induced cytokine gene expression by an
      adenovirus super-repressor IkappaB mutant vector demonstrate that these effects
      were NF-kappaB-dependent. Interestingly, the NF-kappaB-induced expression of
      these transcripts correlates with increased protein levels of NF-kappaB-regulated
      proinflammatory factors in the urine of IC patients in comparison to controls.
      That these factors are capable of activating NF-kappaB in urothelial cells
      suggests a pivotal role for this nuclear transcription factor in the
      pathophysiology of the disease, possibly by inducing aberrant immune and
      inflammatory responses within the bladder of IC patients.

PMID- 14574534
TI  - Why are Foley catheters so vulnerable to encrustation and blockage by crystalline
      bacterial biofilm?
AB  - Many patients undergoing long-term bladder catheterisation experience blockage
      and encrustation of their catheters. The problem stems from infection by urease
      producing bacteria, particularly Proteus mirabilis. Bacterial biofilms colonise
      the catheters, the activity of urease raises the pH and induces the deposition of
      calcium and magnesium phosphate crystals. In this study, a laboratory model of
      the catheterised bladder has been used to examine the early stages in the
      formation of the crystalline biofilms. The results show that initial cell
      adhesion is to the irregular surfaces surrounding the catheter eye-holes.
      Microcolonies form in depressions in these surfaces and spread to cover the
      entire surface of the rims around the eye-holes. Crystals then form around the
      bacterial populations and the biofilm starts to move down the lumenal surfaces of
      the catheters. The encrustation develops most extensively and generally blocks
      the catheter at or just below the eye-hole. There is a need to improve catheter
      design and manufacturing procedures for the eye-holes if the problems associated
      with the current devices are to be reduced.

PMID- 14574535
TI  - Testicular volume and masculine identity in men with unilateral cryptorchidism:
      results of a community-based survey in Korea.
AB  - We determined the influence of cryptorchidism on testicular volume and masculine
      identity in young men living in a community. Of the 27,202 men aged 20 years
      dwelling in the community, we randomly selected a 10% sampling fraction of whom
      2,080 men (a response rate of 77.0%) agreed to participate in the study. All
      volunteers underwent a standard evaluation, including a detailed medical history
      and physical examination. For the evaluation of the influence of cryptorchidism
      on masculine identity, we used the Bem Sex Role Inventory (BSRI). Among
      participants, 38 (1.8%) had cryptorchidism or a history of surgery for
      cryptorchidism (right 15, left 21, bilateral 2). In total, 29 had had undergone
      surgery (mean age at the time of operation; 8.9+/-3.9 years, range; 2-19 years).
      Of 25 men who had undergone orchiopexy due to unilateral cryptorchidism, the
      testicular volume of the affected side was significantly smaller than that of the
      contralateral side. Of the 36 patients with unilateral cryptorchidism, the
      contralateral testicular volume of men who had undergone orchiopexy was not
      different with that of those who had undergone orchiectomy or had not undergone
      surgery. When we compared the scores for masculinity and femininity using the
      BSRI between men with and without testis in the scrotum, there were no
      differences between the two groups. Our results demonstrate that delayed
      orchiopexy does not improve the testicular volume of the affected side or the
      masculine identity in men with unilateral cryptorchidism. In addition, these
      findings suggest that there is a need to increase the awareness of cryptorchidism
      among all parties involved in the health care of children.

PMID- 14574536
TI  - The effects of pentoxifylline on renal function and free radical production in
      unilateral ureteral obstruction.
AB  - There is an ongoing discussion about ureteral obstruction-related renal
      dysfunction. In this study, we aimed to test the effect of pentoxifylline (PTX)
      on both kidneys in unilateral ureteral obstruction (UUO), and to determine its
      interaction of with prostaglandin E2 (PGE2), and diclofenac sodium (DIS). A sham
      operation was performed in group 1. Placebo, PTX, DIS, and PTX+DIS were
      administrated to groups 2, 3, 4 and 5, respectively. The left ureter was ligated
      in all groups except group 1. At 24 h, technetium 99m diethylenetriamine penta
      acetic acid scintigraphy was performed to determine renal function. Additionally,
      the tissue levels of thiobarbituric acid reactive substances (TBARS) and PGE2 in
      both kidneys were measured to determine cytotoxic and cytoprotective mechanisms.
      When the ipsilateral kidneys were evaluated: (1) UUO significantly reduced DTPA
      uptake and none of the medications used prevented the reduction, (2) UUO
      significantly increased TBARS production, and only PTX prevented the increase,
      (3) UUO caused a significant increase in PGE2 production, and only DIS
      significantly decreased this. When the contralateral kidneys were evaluated: (1)
      UUO significantly increased DTPA uptake but DIS and PTX+DIS prevented this, (2)
      UUO significantly elevated TBARS levels and DIS and PTX+DIS caused an additional
      elevation, (3) UUO significantly increased PGE2 production, and only DIS
      prevented this. In conclusion, UUO caused ipsilateral renal hypofunction and
      contralateral hyperfunction, which are related to increased TBARS and PGE2
      levels. PTX markedly decreased free radical activity in the ipsilateral kidney.
      While PTX showed a placebo effect, DIS prevented the compensatory contralateral
      renal response through increased TBARS and decreased PGE2 levels. The beneficial
      effect of PTX on the ipsilateral kidney, and the hazardous effect of DIS on the
      contralateral kidney may be explained by more complex interactions among TBARS,
      PGE2, PTX, DIS and UUO-related renal dysfunction.

PMID- 14574537
TI  - Increased vasoconstrictor reactivity and decreased endothelial function in high
      grade varicocele; functional and morphological study.
AB  - The pathophysiology of human varicocele is not fully understood. We investigated
      vasoconstrictor reactivity, endothelial function and morphological changes in
      different grades of varicocele to clarify the pathophysiology. Contractile
      responses to phenylephrine, norepinephrine, serotonin and histamine were
      determined in isolated human varicose spermatic veins using the organ bath
      technique. Endothelial function was tested with acetylcholine-induced relaxation
      after phenylephrine-induced precontraction in the absence and presence of nitric
      oxide synthase inhibitor, L-NAME, and cyclooxygenase inhibitor, indomethacin. The
      cyclic guanosine monophosphate (cGMP) level was measured in the spermatic vein
      and peripheral plasma. Morphological changes were evaluated with light
      microscopy. Phenylephrine, norepinephrine, serotonin and histamine induced
      concentration-dependent contractions. The maximum contractions for all of these
      agents except norepinephrine were significantly higher in grade III than grade I
      and II (P<0.05). The sensitivity to phenylephrine was significantly higher in
      grades II and III than in grade I (P<0.05). In the presence of L-NAME and
      indomethacin, the difference from respective control phenylephrine-induced
      contractions was higher in grade I and II than grade III. Acetylcholine did not
      induce stable relaxation but the level of cGMP, which is responsible for the
      vasorelaxant effect of NO, in veins was lower in grades II and III than grade I
      (P<0.05). Vessel wall thickness increased in grade II and dilatation developed in
      grade III when compared to grade I (P<0.05). Our findings suggest that
      endothelium produces less vasorelaxant which results in the more enhanced effects
      of vasoconstrictor substances in grade III, indicating that endothelial
      dysfunction develops at high grades of varicocele.

PMID- 14574538
TI  - Neutrophil bactericidal function is defective in patients with recurrent urinary
      tract infections.
AB  - Urinary tract infection (UTI), most frequently caused by Escherichia coli, is one
      of the most common bacterial infections in humans. It is a host inflammatory
      response to bacterial invasion in which large numbers of neutrophils are
      recruited into the bladder in response to cytokines secreted by the infected
      bladder epithelium. We hypothesise that an impaired host neutrophil response
      leads to susceptibility to recurrent UTI (rUTI). Therefore, the neutrophil
      inflammatory response of patients with a history of rUTI was compared to healthy
      controls. No difference in neutrophil adhesion receptor expression or complement
      receptor expression following bacterial stimulus was detected between the two
      groups. However, the expression of the IgG receptor CD16, bacterial phagocytosis
      and reactive oxygen intermediate (ROI) production were significantly reduced in
      UTI patient neutrophils compared to controls. Neutrophils from rUTI patients have
      a significantly reduced bactericidal function when compared to healthy controls,
      with the former showing a reduced capacity for activation. This reduced
      neutrophil function may result in defective bacterial clearance and lead to
      susceptibility to recurrent infection.

PMID- 14574539
TI  - Tumour vascular endothelial growth factor (VEGF) mRNA in relation to serum VEGF
      protein levels and tumour progression in human renal cell carcinoma.
AB  - Angiogenesis is gaining interest because of its importance in tumour growth and
      metastasis. Renal cell carcinoma (RCC) is known to be a well-vascularized tumour.
      The aim of this study was to evaluate the expression of VEGF mRNA and receptor
      flt-1 mRNA (VEGF R1) in a clinical material of RCCs compared with
      clinicopathological variables and serum VEGF levels. Total RNA was extracted from
      snap-frozen tumour tissue obtained from 61 patients. Expression of mRNA for
      VEGF121, VEGF165 and flt-1 were analysed using quantitative RT-PCR. Relative VEGF
      mRNA levels, corrected for corresponding cyclophilin value, were related to
      stage, grade, RCC type and survival time. Serum VEGF165 protein was analysed
      using a quantitative ELISA. Papillary RCC had significantly lower VEGF121 and flt
      1 mRNA levels compared with conventional RCC (p=0.001). VEGF121 mRNA levels were
      significantly lower in locally advanced tumours in relation to tumours limited to
      the kidney and those with metastatic disease (p=0.047 and p=0.036). This
      statistical difference disappeared when only conventional RCCs were evaluated. No
      association was found between VEGF mRNA levels and nuclear grade. Patients with
      lower VEGF121 mRNA levels had significantly longer survival time compared with
      those with higher levels (when adjusted to stage, p=0.0097, log rank test). There
      was an inverse relation between VEGF165 mRNA and serum VEGF165 levels. The trend
      to lower VEGF121 mRNA levels in locally advanced RCC indicate that angiogenic
      activity and degradation might be up-regulated in tumours with a high ability to
      invade. The association with tumour progression shows that VEGF is a promising
      angiogenic factor especially important in conventional RCCs. VEGF expression
      might possibly be of help to identify RCCs susceptible for anti-angiogenic
      therapies.

PMID- 14574540
TI  - Ultrastructural basement membrane topography of the bladder epithelium.
AB  - The basement membrane underlies epithelium and separates it from deeper tissues.
      Recent studies suggest that nanoscale topography of the surface of basement
      membrane may modulate adhesion, migration, proliferation and differentiation of
      overlying epithelium. This study was performed to elucidate nanoscale topographic
      features of basement membrane of the bladder. Bladder tissues were obtained from
      three adult female rhesus macaques. A process was developed to remove the
      epithelium while preserving the underlying basement membrane, and tissues were
      evaluated by immunohistochemistry and scanning electron microscopy (SEM).
      Detailed measurements were made of stereo SEM images to quantitatively define
      topographic features. Measurements made from multiple SEM images of bladder
      basement membrane provided the following values for topographic features: mean
      feature height, 178+/-57 nm; mean fiber diameters, 52+/-28 nm; mean pore
      diameter, 82+/-49 nm; and mean interpore distance (center to center), 127+/-54
      nm. These dimensions are similar to those reported previously for basement
      membranes of other species and anatomical locations. This information provides a
      rational basis for design of nanostructured biomaterials to produce composite
      grafts for repair or replacement of segments of the urinary tract.

PMID- 14574541
TI  - Effects of shock wave lithotripsy on plasma and urinary levels of nitrite and
      adrenomedullin.
AB  - PURPOSE: In this prospective clinical study, we aimed to determine whether
      shockwave lithotripsy (SWL) has any specific effect on plasma as well as urinary
      nitrite, a stabile metabolite of nitric oxide (NO) and adrenomedullin (AM)
      concentrations, and to investigate whether these variables can be used as a
      marker for detecting shockwave-induced impairment of renal tubular and glomerular
      cells. MATERIAL AND METHODS: A total of 20 patients with renal pelvic or caliceal
      stones < or =2 cm undergoing anesthesia-free SWL without auxiliary measures and a
      control group of ten patients without any urological symptoms were included in
      this study. The plasma and urinary concentrations of nitrite and AM were measured
      before, 24 h, and 7 days after SWL. Nitrite levels were measured by Griess
      reaction. Reverse-phase high-performance liquid chromatography (HPLC) was used to
      determine AM levels. RESULTS: Application of high-energy shock waves (HESW) in
      our study caused a statistically significant increase in plasma levels of both NO
      and AM, which reflected an organized response of the kidney to this type of
      trauma in an attempt to maintain normal renal hemodynamics. Mean plasma nitrite
      concentration before SWL application was 29.9+/-7.6 micromol/l and this value was
      found to be 39.02+/-8.45 micromol/l at 24-h follow-up. Comparative evaluation of
      the plasma concentrations of AM revealed a significant increase at the 24-h
      examination: 20.51+/-3.0 pmol/ml and 32.54+/-4.3 pmol/l, respectively. On the
      other hand, comparative evaluation of urinary levels of both nitrite and AM
      levels before as well as 24 h after SWL application revealed a statistically
      significant increase related to markers. CONCLUSION: This first clinical study on
      plasma-urinary nitrite and AM levels in patients undergoing the SWL procedure
      indicated that plasma and urine levels of both peptides were increased. Our
      findings in turn suggested that SWL application to kidney can stimulate the NO
      cGMP signalling pathway to increase NO production in the kidney. Our findings
      also indicated that the increased levels of NO and AM secretion during renal
      parenchymal ischemia may be protective enough for renal pathological alterations
      resulting from SWL-induced renal trauma. We suggest that this increase may be a
      compensatory response to SWL induced injury.

PMID- 14574542
TI  - Effect of botulinum-A toxin to cremaster muscle: an experimental study.
AB  - OBJECTIVE: A controversy exists on the definition, etiology and treatment of the
      retractile testes. In the present experimental study, we aimed to show the effect
      of botulinum-A toxin (Botox) on cremasteric muscle of a rat, and whether it may
      be an alternative to surgical treatment of retractile testis. METHODS: Ten Wistar
      rats were used in the study. By stimulating cremasteric reflex, five compound
      muscle action potentials (CMAP) of the right and left cremasteric muscles of each
      rat were recorded using surface electrodes. Intramuscular injection of botulinum
      A toxin was done to the right side. Saline was injected to the left cremasteric
      muscles, and the left side also served as control. CMAP of the cremasteric
      muscles were recorded 45 days after the injection. Statistical analysis was done
      using Wilcoxon Signed rank test. RESULTS: Mean CMAP of the right side was 3.25+/
      1.39 microV before the injection and 0.44+/-0.25 microV after botulinum-A toxin
      injection. The difference was statistically significant (p<0.05). Mean CMAP on
      the left side was 3.48+/-0.32 microV and 3.14+/-1.12 microV at baseline and the
      end of the study, respectively. The difference was not statistically significant
      (p>0.05). CONCLUSION: The botulinum-A toxin paralyzes the cremasteric muscles of
      the rats. As cremasteric hypertonicity is accepted as one of the reasons for
      retractile testes, botulinum-A toxin injection to cremasteric muscles may be
      helpful in diagnosis and may be an alternative to surgical treatment of this
      pathology in repeated dosages. Long-term evaluation of this paralysis is
      necessary.

PMID- 14574543
TI  - Use of an implantable marker for rapid intraoperative localization of nonpalpable
      tumors: a pilot study in a swine colorectal model.
AB  - BACKGROUND: This study aimed to establish the accuracy and reproducibility of
      localization of intraluminal markers by laparoscopic and open techniques in a
      swine colorectal model, using a prototype for a novel wireless system. METHODS: A
      prototype marker was placed into the colon of an adult pig. The surgeon was
      blinded to placement and localized the marker using a detection probe (3
      surgeons/10 trials/2-D and 3-D systems). RESULTS: Each surgeon was able to
      accurately locate the marker within 28.7 +/- 20.6 (LAP) and 18.3 +/- 6.7 (OPEN)
      sec ( p = 0.013). There were no significant differences between surgeons in
      localization times, regardless of experience. A 3-D interface made no difference
      in accuracy or time (LAP = 35 vs 28 seconds; p = NS [not significant]).
      CONCLUSIONS: This study demonstrates the use of a novel system for intraoperative
      identification of nonpalpable lesions. This technology may have important
      implications in the surgical management of nonpalpable tumors and in applications
      of interventional radiology.

PMID- 14574544
TI  - Gastrointestinal transit after laparoscopic versus open colonic resection.
AB  - BACKGROUND: Multimodal rehabilitation with epidural analgesia, early oral
      nutrition and mobilization, and laxative use has decreased the duration of ileus
      after colonic surgery to about 2 days, as compared with the usual 3 to 5 days of
      rehabilitation required after open surgery and the slightly shorter time required
      with laparoscopic surgery. Gastrointestinal transit after colonic resection with
      laparoscopy or laparotomy was assessed. METHODS: In this study, 32 patients
      randomized to laparoscopic or open colonic resection received 4 MBq of 111indium
      diethylenetriamine pentaacetic acid, a tracer, at the end of surgery. Images of
      the abdomen were obtained 24 and 48 h postoperatively. An opaque abdominal
      dressing blinded care personnel and patients to the procedure. RESULTS:
      Defecation occurred on median day 2 postoperatively in both groups. At 48 h
      postoperatively, 53% of the tracer was excreted by patients in the laparoscopic
      group, as compared with 26% in the open group ( p > 0.05). CONCLUSION:
      Postoperative ileus and gastrointestinal transit normalized within 48 h after
      colonic resection in the patients who received multimodal rehabilitation. No
      significant difference was observed between the patients who underwent the
      laparoscopic procedure and those who underwent the open procedure.

PMID- 14574546
TI  - Virtual reality surgical laparoscopic simulators.

PMID- 14574545
TI  - Umbilical hernia in adults.
AB  - BACKGROUND: There is no consensus on the best technique for the repair of
      umbilical hernia in adults. The role of laparoscopic hernioplasty of umbilical
      hernia remains controversial. This study was undertaken to compare the outcomes
      of open and laparoscopic onlay patch repair of umbilical hernia in adults.
      METHODS: From January 1996 to December 2002, 102 patients underwent elective
      repair of umbilical hernia. Operative techniques included Mayo repair ( n = 43),
      laparoscopic onlay Gore-Tex patch hernioplasty ( n = 26), suture herniorrhaphy (
      n = 24), and mesh hernioplasty ( n = 9). RESULTS: Demographic features and risk
      factors were similar among the four groups. The operative time of laparoscopic
      hernioplasty (median, 66 min) was significantly longer than those for patients
      who underwent Mayo repair (60 min) or sutured herniorrhaphy (50 min) ( p < 0.05).
      None of the patients who underwent laparoscopic patch repairs required conversion
      to open repair. The median pain score at rest on postoperative day 1 was
      significantly lower in patients who underwent laparoscopic repair compared to
      those who had Mayo repair. A significantly shorter hospital stay and a lower
      wound morbidity rate were also observed in patients who underwent laparoscopic
      repair. With a mean follow-up of 2 years, suture herniorrhaphy had a relatively
      high recurrence rate (8.7%), whereas no recurrence was documented for the other
      techniques. CONCLUSIONS: Laparoscopic onlay patch hernioplasty is a safe and
      efficacious technique for the repair of umbilical hernia. Compared to Mayo
      repair, the laparoscopic approach confers the advantages of reduced postoperative
      pain, shorter hospital stay, and a diminished morbidity rate.

PMID- 14574547
TI  - Laparoscopic vs open hepatic resection: a comparative study.
AB  - BACKGROUND: Although the feasibility of minor laparoscopic liver resections (LLR)
      has been demonstrated, data comparing the open vs the laparoscopic approach to
      liver resection are lacking. METHODS: We compared 30 LLR with 30 open liver
      resections (OLR) in a pair-matched analysis. The indications for resection were
      malignant disease in 47% of the LLR and 83% of the OLR. The average size of the
      lesions was 42 mm for LLR and 41 mm for OLR. Five wedge resections, 12
      segmentectomies, and 13 bisegmentectomies were performed in each group. RESULTS:
      The conversion rate for LLR was nil. The mean operative time was 148 min for LLR
      and 142 min for OLR. Mean blood loss was minimal in the LLR group (320 vs 479 ml;
      p < 0.05). Postoperative complications occurred in 6.6% of the patients in each
      group; there were no deaths. The mean postoperative hospital stay was shorter for
      LLR patients (6.4 vs 8.7 days; p < 0.05). In tumors, the resection margin was <1
      cm in 43% of the LLR patients and 40% of the OLR patients ( p = NS). CONCLUSIONS:
      Minor LLR of the anterior segments has the same rates of mortality and morbidity
      as OLR. However, the laparoscopic approach reduces blood loss and postoperative
      hospital stay.

PMID- 14574548
TI  - Minimally invasive endoscopic-assisted parathyroidectomy for primary
      hyperparathyroidism.
AB  - BACKGROUND: Minimally invasive surgery for primary hyperparathyroidism (pHPT)
      depends on both an accurate preoperative localization and the availability of
      intraoperative parathyroid hormone monitoring. METHODS: Patients with sporadic
      pHPT and one unequivocally enlarged parathyroid gland on preoperative imaging
      underwent endoscopic-assisted parathyroidectomy. Intraoperative rapid parathyroid
      hormone (quick PTH) monitoring was performed, and surgical success was confirmed
      when there was a >50% decrease in quick PTH level 10 min after excision as
      compared with the baseline level at induction. The surgical outcome and the use
      of preoperative localization, together with the role played by quick PTH assay in
      enhancing the operative success, were evaluated. RESULTS: From 1999 to 2002, 66
      of 107 patients (62%) were selected for this approach. The accuracy of 99mTc
      Sestamibi scintigraphy and ultrasonography was 97% and 70%, respectively.
      Conversion was required in four cases due to technical problems, and four
      additional patients failed to show a significant decline in quick PTH levels
      postexcision. Two patients underwent cervical exploration without the finding of
      any additional pathology, and another two patients had a delayed drop in quick
      PTH that was confirmed 30 min postexcision. All patients had a solitary adenoma
      and were cured of hypercalcemia during a median follow-up of 9 months.
      CONCLUSIONS: Minimally invasive endoscopic-assisted parathyroidectomy can be
      performed expeditiously in a select group of patients based on 99mTc-Sestamibi
      scintigraphy. The use of quick PTH assay can ensure surgical success, but careful
      interpretation of the results is mandatory.

PMID- 14574549
TI  - Film analysis of activated sludge microbial discs by the Taguchi method and grey
      relational analysis.
AB  - A biofilm model with substrate inhibition is proposed for the activated sludge
      growing discs of rotating biological contactor (RBC); this model is different
      from the steady-state biofilm model based on the Monod assumption. Both deep and
      shallow types of biofilms are examined and discussed. The biofilm models based on
      both Monod and substrate inhibition (Haldane) assumptions are compared. In
      addition, the relationships between substrate utilization rate, biofilm
      thickness, and liquid phase substrate concentration are discussed. The influence
      order of the factors that affect the biofilm thickness is studied and discussed
      by combining the Taguchi method and grey relational analysis. In this work, a
      Taguchi orthogonal table is used to construct the series that is needed for grey
      relational analysis to determine the influence priority of the four parameters
      S(B), kX(f), K(s), and K(i).

PMID- 14574550
TI  - Adhesive interactions between CD34(+)-derived dendritic cell precursors and
      dermal microvascular endothelial cells studied by scanning electron microscopy.
AB  - Dendritic cells are migratory cells. Before they extravasate from the circulation
      into the skin across capillary blood vessel walls, they have to interact with
      endothelial cells. Using a fluorimetric adhesion assay, we have recently shown
      that CD34(+)-derived dendritic cell precursors are able to bind to resting and
      stimulated dermal microvascular endothelial cells. In the present study, we
      attempted to visualize this process at an ultrastructural level. CD34(+)
      progenitor cells were purified from human cord blood samples by means of
      immunomagnetic beads, and dendritic cells were generated by culture in the
      presence of GM-CSF, TNF-alpha and hSCF for 5 days. Immature CD83(-) CD86(low)
      dendritic cells were added to human dermal microvascular endothelial cells grown
      to confluence on membrane chambers. After 2 h, unbound dendritic cell precursors
      were removed, and bound cells were prepared for routine scanning electron
      microscopy. We found that (1). dendritic cell precursors firmly adhere to
      microvascular endothelial cells, enveloping them with their surface processes;
      (2). dendritic cell precursors are extremely deformable as they squeeze through
      the dense network of microvascular endothelial cells; (3). microvascular
      endothelial cells form, in part, a multi-layered network rather than the typical
      cobblestone pattern as seen by phase-contrast microscopy. The morphology of
      dendritic cell precursors and of human dermal microvascular endothelial cells was
      examined here, for the first time, by scanning electron microscopy. These data
      further emphasize that CD34(+)-derived dendritic cells efficiently adhere to
      dermal microvascular endothelial cells.

PMID- 14574551
TI  - Vascular remodeling by intussusceptive angiogenesis.
AB  - Intussusception (growth within itself) is an alternative to the sprouting mode of
      angiogenesis. The protrusion of opposing microvascular walls into the capillary
      lumen creates a contact zone between endothelial cells. The endothelial bilayer
      is perforated, intercellular contacts are reorganized, and a transluminal pillar
      with an interstitial core is formed, which is soon invaded by myofibroblasts and
      pericytes leading to its rapid enlargement by the deposition of collagen fibrils.
      Intussusception has been implicated in three processes of vascular growth and
      remodeling. (1) Intussusceptive microvascular growth permits rapid expansion of
      the capillary plexus, furnishing a large endothelial surface for metabolic
      exchange. (2) Intussusceptive arborization causes changes in the size, position,
      and form of preferentially perfused capillary segments, creating a hierarchical
      tree. (3) Intussusceptive branching remodeling (IBR) leads to modification of the
      branching geometry of supplying vessels, optimizing pre- and postcapillary flow
      properties. IBR can also lead to the removal of branches by pruning in response
      to changes in metabolic needs. None of the three modes requires the immediate
      proliferation of endothelial cells but rather the rearrangement and plastic
      remodeling of existing ones. Intussusception appears to be triggered immediately
      after the formation of the primitive capillary plexus by vasculogenesis or
      sprouting. The advantage of this mechanism of growth over sprouting is that blood
      vessels are generated more rapidly in an energetically and metabolically more
      economic manner, as extensive cell proliferation, basement membrane degradation,
      and invasion of the surrounding tissue are not required; the capillaries thereby
      formed are less leaky. This process occurs without disrupting organ function.
      Improvements in our understanding of the process should enable the development of
      novel pro- and anti-angiogenic therapeutic treatments.

PMID- 14574554
TI  - Endoparasite KC5/2 encloses large areas of sol-like cytoplasm within
      Acanthamoebae. Normal behavior or aberration?
AB  - In addition to the characteristic development of the rod-shaped or tube-like
      endocytobionts replicating within the sol-like cytoplasm of acanthamoebae which
      was published recently (Michel et al. 2003) we observed the strange behavior of
      the endoparasites described as follows. The material normally forming the
      characteristic cell walls of KC5/2 organisms was found to form a long array along
      the borderline between the granuloplasm and the central homogenous sol-like
      cytoplasm, so that about one third of the sol plasm had already been surrounded.
      We do not know whether this process belongs to the normal developmental
      repertoire of the endocytobiont that was interrupted by fixation for electron
      microscopy, or whether it is an aberrant behavior.

PMID- 14574555
TI  - Prevalence of intestinal parasite infections on a national scale among primary
      schoolchildren in Laos.
AB  - In order to investigate the epidemiological situation of intestinal parasite
      infections in Laos, parasitological surveys were carried out on a national scale
      including 17 provinces and the Vientiane Municipality. A total of 29,846 stool
      specimens were collected from primary schoolchildren from May 2000 to June 2002
      and examined once with the cellophane thick smear technique. The cumulative egg
      positive rate for intestinal helminths was 61.9%. By species, the rate for
      Ascaris lumbricoides was 34.9%, hookworm 19.1%, Trichuris trichiura 25.8%,
      Opisthorchis viverrini 10.9%, Taenia spp. 0.6% and Hymenolepis spp. 0.2%. The
      northern mountainous regions such as Phongsaly, Huaphan or Saysomboune Province
      showed a higher prevalence (over 70%) of soil- transmitted helminths. The regions
      along the Mekong River such as Khammuane, Saravane or Savannakhet Province showed
      a higher prevalence (over 20%) of fish-borne parasites. On the other hand,
      Schistosoma mansoni eggs were detected in 1.7% of schoolchildren only in
      Champassak Province, a previously endemic area. The highest prevalence was noted
      in Phongsaly Province (96.0%) and the lowest in Bolikhamxay Province (27.5%). An
      additional small-scale survey by cellophane anal swab detected Enterobius
      vermicularis eggs in 35.7% of 451 schoolchildren aged 6-8 years in Khammuane,
      Vientiane, Champassak Province and the Vientiane Municipality. Meanwhile, the
      mean blood haemoglobin level of hookworm-infected children was not lower than
      that of children not infected with hookworm, suggesting that nutritional factors
      are more important than parasite infection per se. Nevertheless, the above
      results indicate that a nationwide parasite control project is necessary to
      reduce possible morbidity due to parasitic diseases in the country.

PMID- 14574556
TI  - Ecto-ATPase activity on the surface of Trypanosoma cruzi and its possible role in
      the parasite-host cell interaction.
AB  - This study describes the possible role of Mg(2+)-dependent ecto-ATPase activity
      on the Trypanosoma cruzi-host cell interaction. Mg(2+)-dependent ecto-ATPase
      activity is observed on the cell body and flagellar membranes of the parasite and
      is about 20 times greater in trypomastigotes, as compared with epimastigotes.
      Suramin (a competitive antagonist of P2 receptors) and the impermeant agent 4,4'
      diisothiocyanostylbene 2',2'-disulfonic acid (DIDS), both inhibitors of ecto
      ATPases, strongly inhibited ATPase activity and the adhesion and internalization
      of both evolutive forms by mouse resident macrophages. Suramin inhibited the
      growth of epimastigotes, suggesting a direct participation of ecto-ATPase
      activity in this process. To overcome the presence of suramin in the culture
      medium during the time of growth, Mg(2+) ecto-ATPase activity was enhanced 4
      fold, as compared with control parasites. The over-expression in enzyme activity
      was followed by a dramatic increase in the adhesion of epimastigotes to resident
      macrophages above the level observed for non-treated parasites.

PMID- 14574558
TI  - Metazoan parasites and feeding behaviour of four small-sized fish species from
      the central North Sea.
AB  - The metazoan parasites and stomach contents of the small-sized demersal fishes
      Agonus cataphractus, Buglossidium luteum, Callionymus lyra and Rhinonemus
      cimbrius were studied and analysed. The fishes were captured using various
      sampling gears at 12 stations in the central North Sea. A total of 16 metazoan
      parasite species were isolated: six adult Digenea, three larval and adult
      Cestoda, four larval and adult Nematoda and three larval and adult Crustacea.
      With nine parasites species each, A. cataphractus and R. cimbrius harboured the
      highest parasite diversity, while B. luteum and C. lyra hosted only six and five
      parasite species, respectively. Eighteen new hosts and four new locality records
      were established. No Myxozoa, Monogenea or Acanthocephala were found. Most of the
      detected parasites showed a wide geographical range and a low host-specificity.
      The composition of the parasite fauna differed between the fish species, in
      accordance with their different feeding behaviours. The diet of bentho-pelagic
      feeders ( A. cataphractus, R. cimbrius) was more diverse in comparison with the
      more specialised benthic feeders ( C. lyra, B. luteum). This correlated with the
      lower diversity of heteroxenic parasites within both small-sized benthic fish
      species.

PMID- 14574557
TI  - Analysis of the genes expressed in Clonorchis sinensis adults using the expressed
      sequence tag approach.
AB  - Clonorchis sinensis is a biliary tract parasite, which infects over 30 million
      people in China, Korea and Southeast Asia through the ingestion of undercooked
      freshwater fish that harbour the infective metacercariae. The genes expressed in
      C. sinensis adults were identified in order to develop novel drugs, better
      diagnostics and vaccines for the parasite. The C. sinensis cDNA library was
      constructed and DNA sequencing was performed with 450 randomly selected clones.
      Four hundred and fifteen clones contained the amino-acid-encoding sequences. The
      functions of these genes could be assigned by DNA sequence homology. Basic Local
      Alignment Search Tool X analysis showed that 277 of the 415 clones were strongly
      matched ( P<10(-9)) to previously identified proteins, while the remaining 138
      fell into the "no database match" category. Among the clones matching previously
      identified proteins, 220 putatively identified genes were sorted into seven
      functional categories. These included the genes associated with energy metabolism
      (38), gene expression/RNA metabolism (21), regulatory/signalling components (14),
      protein metabolism/sorting (98), the structure/cytoskeleton (29), membrane
      transporters (ten) and antigenic proteins (ten). The remaining 57 clones were not
      included in these categories. The dataset included the genes encoding the
      proteases, a lipid binding protein, the antigen proteins and the other genes of
      interest from a diagnostics, drug or vaccine development viewpoint. The present
      expressed sequence tag analysis proved to be an effective tool for examining gene
      expression and identified several important genes which increase and complement
      our knowledge of the biology of C. sinensis.

PMID- 14574559
TI  - Investigations on the biology, epidemiology, pathology and control of Tunga
      penetrans in Brazil: III. Cytokine levels in peripheral blood of infected humans.
AB  - Tungiasis is caused by penetration of the female jigger flea, Tunga penetrans,
      into the skin of its host. This parasitic skin disease is almost invariably
      associated with intense inflammation around embedded fleas, the underlying
      mechanisms being unknown. A study was undertaken to determine whether the
      inflammatory process can be attributed to immune activation induced by a
      biologically active foreign body. We determined the concentrations of Th1
      mediated (IFN-gamma, TNF-alpha) and Th2-mediated (IL-4) cytokines in the sera of
      patients with tungiasis. The results were compared with those of controls
      infected with different helminths or exposed to soil-transmitted helminths. The
      results show that tungiasis causes a mixed Th1 and Th2 immune response,
      characterized by significantly increased concentrations of the pro-inflammatory
      cytokines IFN-gamma and TNF-alpha, with a slightly increased concentration of IL
      4. The preponderance of the Th1 immune response was indicated by a significantly
      increased TNF-alpha/IL-4 ratio in patients with tungiasis, as compared with the
      control groups.

PMID- 14574560
TI  - The rabbit coccidium Eimeria flavescens Marotel and Guilhon, 1941: an electron
      microscopic study of its life cycle.
AB  - The endogenous cycle of Eimeria flavescens was studied in specific pathogen-free
      rabbits by means of histology and transmission electron microscopy. In total,
      five asexual generations were observed and two types of meronts and merozoites
      were found in each generation. Type A gave rise to a smaller number of thick
      polynucleate merozoites in which daughter merozoites were formed by endomerogony,
      while in the type B meronts slender uninucleate merozoites arose from
      ectomerogony. The first generation meronts were found in the crypts and proximal
      part of the villi of the duodenum and jejunum, whereas the three following
      generations developed in the superficial epithelium of the large intestine
      (cecum, vermiform appendix and colon). The last merogony as well as gamogony took
      place in crypts of the large intestine.

PMID- 14574561
TI  - Field test data on small strongyles in evaluation of activity of fenbendazole
      given once a day for 5 consecutive days to thoroughbred yearlings on two farms in
      Kentucky in 2002 and 2003.
AB  - Fenbendazole (FBZ) suspension was administered intraorally at the dose rate of
      7.0-10.3 mg/kg once a day for 5 consecutive days to 58 thoroughbred yearlings on
      two farms in central Kentucky in April, 2002. The average dose rates of drug
      given to groups of colts and fillies on each farm were 7.8-8.5 mg/kg. Only 3 of
      the yearlings had negative counts of strongyle eggs per gram of feces (EPGs)
      after treatment which was at 8.4, 8.7, or 9.4 mg/kg; the pretreatment EPG counts
      were low (10-30). Reduction of EPG values at the highest dose rates was 0% (at
      9.5 mg/kg) and 78% (at 10.3 mg/kg). This study was repeated in April, 2003 in 38
      thoroughbred yearlings on one of the two same farms used in the 2002 research,
      but all horses were treated at the same dose rate (10 mg/kg) of FBZ paste once
      daily for 5 consecutive days. Only 1 of these yearlings had a negative EPG count
      after treatment, but this value was also negative before treatment. Reductions of
      EPG counts after treatment ranged from 0% to 85% (mean =22%) for the colts and
      from 0 to 63% (mean =14%) for the fillies. Examination of cultures of fecal
      samples from these yearlings revealed that only small strongyle larvae were
      present. There was obvious FBZ-resistance of the small strongyles in yearlings on
      both farms at the dose rates used.

PMID- 14574562
TI  - Sustained-release praziquantel tablet: pharmacokinetics and the treatment of
      clonorchiasis in beagle dogs.
AB  - Praziquantel is rapidly absorbed and secreted; and thus fractional doses are
      recommended for the treatment of cestode and trematode infections. In the present
      study, we developed a new praziquantel tablet formula allowing sustained-release
      (SRP). In vitro dissolution of SRP tablets showed that praziquantel at 300
      mg/tablet combined with hydroxypropyl methylcellulose dissolved completely at a
      constant rate over 10 h, whereas the conventional praziquantel tablet (PZQ) was
      only 40% dissolved. Pharmacokinetic studies in dogs confirmed that SRP was
      absorbed more slowly than PZQ. The mean value of the area under the
      concentration/time curve from 0 h to the final observation time, the maximum
      concentration in serum, and the time of maximum concentration in serum for SRP
      were 3,471,500 ng/min for 0.25 ml, 10,300 ng for 0.25 ml, and 192 min, while the
      values for PZQ were 688,600 ng/min for 0.25 ml, 2,500 ng for 0.25 ml, and 135
      min. The cure rate in dogs with a heavy infection (500 metacercariae) treated
      with a single dose of SRP (150 mg/tablet) at 50 mg/kg was 80%, while in dogs
      treated with a single dose of SRP (300 mg/tablet) at 30 mg/kg it was 60%, and the
      cure rate with PZQ was 20%. In each case, the egg reduction rate was similar
      (over 90%). No abnormal liver functions or hepatic or renal pathologies were
      observed in dogs administered with SRP at 30 mg/kg. The SRP tablet showed
      sustained release and slow absorption; and it had an improved anthelmintic
      efficacy against Clonorchis sinensis in experimental dogs, compared with
      conventional praziquantel.

PMID- 14574563
TI  - Nematocidal activity of nitazoxanide in laboratory models.
AB  - The nematocidal activity of a broad-spectrum antiparasitic agent, nitazoxanide [(
      N-(5-nitrothiazol-2-gammal)salicylamide; NTZ], was evaluated in both in vitro and
      in vivo models using Caenorhabditis elegans, Heligmosomoides polygyrus and
      Trichinella spiralis. In vitro, NTZ (100 muM) exhibited a low activity against C.
      elegans and had no effect on embryonation and hatching of H. polygyrus eggs. At
      concentrations of 100 and 50 muM, the inhibition of excretion/secretion of
      acetylcholinesterase and acid phosphatase of adult H. polygyrus by NTZ was
      variable. The in vitro effects of mebendazole (5 muM), albendazole (1 muM) and
      levamisole (10 muM) were superior to those of NTZ. In mice, NTZ at 1 g/kg proved
      to be inactive against preadults of T. spiralis whereas mebendazole at 10 mg/kg
      reduced the worm burden by up to 83%. NTZ at 1 g/kg per day for 3 consecutive
      days showed a low activity against adults of H. polygyrus (21% reduction).
      Levamisole, at a single dose of 10 mg/kg, reduced the worm burden by up to 89.9%.
      The results of this study suggest that NTZ would not have met criteria of a
      candidate compound.

PMID- 14574564
TI  - Characterisation of Fasciola gigantica adult 27-kDa excretory-secretory antigen
      in human fascioliasis.
AB  - The 27-kDa excretory-secretory antigen partially purified from adult Fasciola
      gigantica adult worms (FG27) has been used as the sensitive and specific antigen
      for immunodiagnosis of human fascioliasis. Lectin-blot analyses have shown that
      the FG27 possesses both N - and O -glycans. In two-dimensional electrophoresis,
      silver staining, lectin blotting and immunoblotting, FG27 displayed at least four
      antigenic-glycosylated protein spots at the pI values of 4.8, 4.9, 5.2 and 5.4,
      respectively. After removing glycan moieties from the antigen by alkaline
      treatment, the molecular mass of the FG27 was reduced to 26.5 kDa as a prominent
      deglycosylated band. Immunoblotting analysis has revealed that the 26.5-kDa band
      reacts with the pooled human fascioliasis sera without any loss of antigenicity.
      These results suggest that the major antigenicity of the FG27 is due to its
      protein epitopes.

PMID- 14574566
TI  - Immunological comparison of 124 isolates of Toxoplasma gondii.
AB  - We tested 124 isolates of Toxoplasma gondii, as determined morphologically and by
      their ability to elicit antibodies in the dye test with the RH strain of
      Toxoplasma in mice. They were compared for their capacity to immunize CF-1 mice
      against isolate T-1, and T-1 immune mice for their capacity to resist each of the
      123 other isolates. Of the 125 isolates, 52 had been isolated in the continental
      USA, 33 in Central America, 15 in Europe, 9 in Hawaii, five in Japan, two in
      Taiwan, five in Australia, one in Indonesia, one in Tunisia, and one was of
      unknown origin. Complete cross-immunity was found. This suggests that only one
      immunotype of Toxoplasma is prevalent in the United States, and perhaps all over
      the earth. Vaccines are likely to immunize against most or all Toxoplasma
      isolates.

PMID- 14574565
TI  - Prevalence of natural ovine fasciolosis shown by demonstrating the presence of
      serum circulating antigens.
AB  - The prevalence of fasciolosis in sheep (Galicia, Northwest Spain) kept under
      field conditions was determined by using a sandwich-enzyme-linked immunosorbent
      assay (sELISA). Serum Fasciola hepatica circulating antigens were captured by
      means of a rabbit polyclonal IgG antibody to F. hepatica excretory/secretory
      products. Results were compared to those obtained by faecal sedimentation and an
      indirect ELISA (iELISA) and excretory/secretory antigens. Prevalences were 39.1%
      by sELISA, 30.4% by faecal sedimentation and 56% by iELISA; 83.3% of the sheep
      were positive to any one of the three tests. We observed that 59.5% of the sheep
      examined had active fasciolosis, 29.1% (117) had antigenaemia, 20.4% (82) passed
      eggs, and 40 (10%) were positive to both probes. We conclude that there is a high
      prevalence of fasciolosis in sheep from the studied region, and that the
      combination of sELISA and coprological sedimentation is extremely helpful for
      demonstrating current fasciolosis, so its application can be strongly recommended
      for epidemiological surveys.

PMID- 14574567
TI  - Cloning and characterization of Clonorchis sinensis myoglobin using immune sera
      against excretory-secretory antigens.
AB  - Clonorchis sinensis excretory-secretory (ES) antigens were separated by gradient
      SDS-PAGE and the antigenic protein isolated at 21 kDa was injected into rats. A
      C. sinensis cDNA library was then immunoscreened with sera from the 21-kDa
      antigenic protein-immunized rats. The selected genes, which were named C.
      sinensis myoglobin, contained a single open reading frame of 450 base pairs
      encoding 150 amino acids. A single hybridized band of 0.57 kb and two to four
      hybridized bands were detected by Northern and Southern blotting. Purified
      recombinant C. sinensis myoglobin was recognized by clonorchiasic rabbit sera
      (50%) and clonorchiasic human sera (25%). An indirect immunofluorescence assay
      showed that C. sinensis myoglobin is distributed over the whole body of the adult
      worm. It is believed that the abundance of C. sinensis myoglobin plays an
      important role as an oxygen reservoir under anaerobic conditions.

PMID- 14574568
TI  - Morbidity and immune response to natural schistosomiasis in baboons ( Papio
      anubis).
AB  - The morbidity and immunological response to naturally acquired Schistosoma
      mansoni infection in a population of wild baboons ( n=28) was investigated. Serum
      obtained from the baboons was assayed for adult worm (SWAP) and schistosome egg
      (SEA)-specific immunoglobulin (Ig)G and IgM antibodies. The animals were
      euthanised, perfused to recover adult schistosome worms and schistosome-related
      pathology was assessed. Nineteen animals (68%) had high serum levels of SWAP
      specific IgG antibodies and 15 (54%) had high levels of SEA-specific IgG
      antibodies. Nine animals (32%) had high levels of SWAP-specific IgM antibodies
      and six (21%) had high levels of SEA-specific IgM antibodies. Mild schistosome
      related pathology was noted in 18 animals (64%). However, adult schistosome worms
      were recovered from only three animals (10%). The results indicate a high
      exposure to schistosomiasis for free-ranging baboons inhabiting an endemic area,
      as evidenced by the high prevalence of parasite-specific humoral antibody
      response. However, this high exposure is associated with low worm recovery and
      mild pathology. In addition, parasite-specific IgM antibodies provided a good
      indicator of an active schistosome infection.

PMID- 14574569
TI  - A first infection of Galba truncatula with Fasciola hepatica modifies the
      prevalence of a subsequent infection and cercarial production in the F1
      generation.
AB  - Snails from two populations highly susceptible to Fasciola hepatica and their F1
      generations were subjected to individual bimiracidial exposures to determine if
      changes noted in infection parameters were due to an effect imposed on the snail
      by the parasite, or to some other effect such as the food used for the snails.
      Apart from the higher survival of unexposed parents at day 30 post exposure
      (p.e.) and their higher shell heights at day 45 p.e., the differences between the
      survival rates of exposed parents, prevalences of infections, and shell sizes
      were not significant. In the F1 snails born to previously infected parents, the
      prevalences of F. hepatica infection and cercarial production were significantly
      lower than those noted for the F1 born to unexposed parents. The survival of
      these snails and their shell growth did not show any significant variation. The
      F1 snails born to previously exposed snails would have developed a partial
      resistance against F. hepatica and this process would probably be maximal in the
      first 2 weeks of larval development inside the snail.

PMID- 14574570
TI  - Expression of a novel lacrimal gland gene lacritin in human breast tissues.
AB  - PURPOSE: The purpose of this study was to examine breast tumors and normal breast
      tissues for the expression of the glycoprotein lacritin. The mRNA and protein
      expression of lacritin has been reported to be restricted to the lacrimal gland.
      METHODS: We investigated 37 human primary invasive breast tumors, seven breast
      cancer cell lines and 16 normal breast tissues by quantitative real-time PCR for
      lacritin expression. RESULTS: We detected lacritin transcripts in 51% (19/37) of
      the primary invasive breast tumors, in 71% (5/7) of the breast cancer cell lines,
      and also in 56% (9/16) of the normal breast tissues. No lacritin mRNA was
      detectable in peripheral blood of healthy individuals. CONCLUSIONS: Here we show
      by quantitative real-time PCR that lacritin is expressed in human breast tumors,
      breast cancer cell lines, and normal breast. The previously reported restricted
      expression pattern of lacritin is therefore incorrect. Lacritin transcripts were
      not detected in peripheral blood which makes lacritin a potential candidate as a
      breast cancer marker gene.

PMID- 14574571
TI  - Technology challenges in screening single gene disorders.
AB  - The completion of the human genome project and the accelerated discovery of genes
      responsible for single gene disorders will allow for the preventive screening of
      carriers and patients. Accuracy and reliability of analytic tests are major
      demands on technologies used in a diagnostic screening environment. The
      consistency of results and the potential of multiplexing suggest mass
      spectrometry as the method of choice for large-scale genetic screening programs.
      The added ability to analyze other large molecules such as peptides and proteins
      further underlines the versatility and usefulness of this technology. We describe
      the use of mass spectrometry for screening of sickle cell disease at the level of
      DNA and protein. CONCLUSION: Analytic methods are needed for large-scale
      screening and diagnostic applications that are highly accurate, fully automated
      and cost-effective. The precise measurement of molecular weights and the use of
      high fidelity enzymes to produce diagnostic products make mass spectrometry the
      method of choice for DNA and protein screening procedures.

PMID- 14574572
TI  - Notochord segmentation may lay down the pathway for the development of the
      vertebral bodies in the Atlantic salmon.
AB  - This study indicates that the development of the vertebrae in the Atlantic salmon
      requires the orchestration of two sources of metameric patterning, derived from
      the notochord and the somite rows, respectively. Before segmentation of the
      salmon notochord, chordoblasts exhibit a well-defined cell axis that is uniformly
      aligned with the cranio-caudal axis. The morphology of these cells is
      characterised by a foot-like basal projection that rests on the notochordal
      sheath. Notochordal segments are initially formed within the chordoblast layer by
      metameric change in the axial orientation of groups of chordoblasts. This process
      results in the formation of circular bands of chordoblasts, with feet
      perpendicular to the cranio-caudal axis, the original chordoblast orientation.
      Each vertebra is defined by two such chordoblast bands, at the cranial and caudal
      borders, respectively. Formation of the chordoblast segments closely precedes
      formation of the chordacentra, which form as calcified rings within the adjacent
      notochordal sheath. Sclerotomal osteoblasts then differentiate on the surface of
      the chordacentra, using them as foundations for further vertebral growth. Thus,
      the morphogenesis of the rudiments of the vertebral bodies is initiated by a
      generation of segments within the chordoblast layer. This dual segmentation model
      for salmon, in which the segmental patterns of the neural and haemal arches are
      somite-derived, while the vertebral segments seem to be notochord-derived,
      contrasts with current models for avians and mammals.

PMID- 14574573
TI  - Levels of oxidative stress and redox-related molecules in the placenta in
      preeclampsia and fetal growth restriction.
AB  - Recent evidence suggests that oxidative stress is involved in the pathophysiology
      of preeclampsia. Using immunohistochemistry and Western blotting, we investigated
      the oxidative stress- and redox-related molecules, such as 8-hydroxy-2'
      deoxyguanosine (8-OHdG), 4-hydroxynonenal (4-HNE), thioredoxin (TRX) and redox
      factor-1 (ref-1) in the placenta in preeclampsia, intrauterine growth restriction
      (IUGR), preeclampsia + IUGR and in normal pregnancy. Using immunohistochemistry,
      the level of 8-OHdG was significantly higher in IUGR ( P=0.012) or preeclampsia +
      IUGR (P=0.0021) than in normal pregnancy, while TRX expression was significantly
      higher in preeclampsia (P=0.045), and ref-1 expression was significantly higher
      in preeclampsia (P=0.017), IUGR (P=0.016) and preeclampsia + IUGR (P=0.0038) than
      in normal pregnancy. The levels of 4-HNE did not differ significantly between
      either preeclampsia or IUGR and normal pregnancy. A significant positive
      correlation was observed between TRX and ref-1 expressions in both normal
      (rho=0.52) and complicated (rho=0.43) pregnancies. Using Western blotting, ref-1
      expression tended to be higher in complicated pregnancies than in normal
      pregnancy (P=0.09). These results suggest that oxidative DNA damage is increased
      in IUGR and that redox function is enhanced in both preeclampsia and IUGR
      compared with normal pregnancy.

PMID- 14574574
TI  - Gene expression at early stages of Brassica napus seed development as revealed by
      transcript profiling of seed-abundant cDNAs.
AB  - Approximately 5000 plaques derived from a Brassica napus L. (canola) seed-cDNA
      library representing 15 days after pollination (DAP) were differentially screened
      for highly expressed genes at the early stages of seed development. Analysis of
      104 differentially expressed sequence tags revealed 54 unique genes, of which 33
      had putative homologues described in Arabidopsis thaliana (L.) Heynh. or B.
      napus. These encoded diverse proteins, ranging from proteins of unknown function
      to metabolic enzymes and proteins associated with cell structure and development.
      Twenty-five genes were only expressed in seeds, and 11 of these started to
      express as early as 5 or 10 DAP. The majority of the seed-specific genes that are
      expressed at early stages of seed development encoded proteins with high
      similarity to hypothetical Arabidopsis proteins. Tissue-specificity determined by
      Northern analysis revealed that four seed-specific genes were expressed only in
      seed coats and another five in both embryos and seed coats. Analysis of
      transcript profiles of seed-abundant as well as seed-specific genes, and their
      expression patterns, implies that the B. napus seed is undergoing an active cell
      proliferation during 10-20 DAP, while establishing metabolic networks for
      subsequent seed maturation.

PMID- 14574576
TI  - Treatment of advanced rectal cancer in a patient after combined pancreas-kidney
      transplantation.
AB  - BACKGROUND: Organ transplantation is a standard procedure today. Due to
      immunosuppressive drugs and increasing survival after organ transplantation,
      patients with transplanted organs carry an increased risk of developing malignant
      tumours. Accordingly, more patients with malignant tumours after transplantation
      will be faced by general or oncology surgeons. We report the case of a 48-year
      old patient with advanced rectal cancer 6.5 years after pancreas-kidney
      transplantation for type I diabetes. METHOD: The patient was treated with neo
      adjuvant radio-chemotherapy, followed by low anterior rectal resection with total
      mesorectal excision. Consecutively, a solitary hepatic metastasis, a solitary
      pulmonary metastasis and a chest wall metastasis were resected over the course of
      13 months. RESULT: The patient eventually died of metastasized cancer 32 months
      after therapy had been initiated, his organ grafts functioning well until his
      death. CONCLUSION: Our case report provides evidence that transplantation
      patients should receive standard oncology treatment, including neo-adjuvant
      treatment, so long as their general condition and organ graft functions allow us
      to do so, although a higher degree of morbidity might be encountered.

PMID- 14574575
TI  - Inhibition of endogenous trypsin- and chymotrypsin-like activities in transgenic
      lettuce expressing heterogeneous proteinase inhibitor SaPIN2a.
AB  - SaPIN2a, a proteinase inhibitor II from American black nightshade (Solanum
      americanum Mill.) is highly expressed in the phloem and could be involved in
      regulating proteolysis in the sieve elements. To further investigate the
      physiological role of SaPIN2a, we have produced transgenic lettuce (Lactuca
      sativa L.) expressing SaPIN2a from the CaMV35S promoter by Agrobacterium-mediated
      transformation. Stable integration of the SaPIN2a cDNA and its inheritance in
      transgenic lines were confirmed by Southern blot analysis and segregation
      analysis of the R1 progeny. SaPIN2a mRNA was detected in both the R0 and R1
      transformants on northern blot analysis but the SaPIN2a protein was not detected
      on western blot analysis using anti-peptide antibodies against SaPIN2a. Despite
      an absence of significant inhibitory activity against bovine trypsin and
      chymotrypsin in extracts of transgenic lettuce, the endogenous trypsin-like
      activity in each transgenic line was almost completely inhibited, and the
      endogenous chymotrypsin-like activity moderately inhibited. Our finding that
      heterogeneously expressed SaPIN2a in transgenic lettuce inhibits plant endogenous
      protease activity further indicates that SaPIN2a regulates proteolysis, and could
      be potentially exploited for the protection of foreign protein production in
      transgenic plants.

PMID- 14574577
TI  - Relationship between muscle architectural features and oxygenation status
      determined by near infrared device.
AB  - This study tested whether regional differences in oxygenation status could result
      from differences in muscle fiber architecture. Architectural properties, oxygen
      supply, and consumption in the medial head of the gastrocnemius muscle (GM) were
      determined in vivo in six men using B-mode ultrasound and functional near
      infrared (NIR) imaging devices. Fascicle length, fascicle angle, NIR-O(2)
      saturation (deoxygenated Hb or oxygenated Hb), and NIR-blood volume (sum of
      deoxygenated and oxygenated Hb) were obtained in the distal and proximal portions
      of the GM at rest and during contraction. Exercise consisted of 2 min of standing
      plantar flexion at 1 Hz with an additional load of 50% of each subject's weight.
      Plantar flexion produced larger decreases (Delta: difference between rest and
      exercise values) in NIR-O(2) saturation [mean saturation (SD) of 0.14 (0.05) vs
      0.07 (0.04) optical density units] and NIR-blood volume [mean saturation (SD) of 
      0.23 (0.08) vs -0.13 (0.04) optical density units] in the distal compared with
      the proximal portion ( P<0.05 for all comparisons). It also produced larger
      changes (Delta) in fascicle length [mean length (SD) of -16.5 (4.7) vs -8.2 (4.2)
      mm] and fascicle angle (mean angle (SD) of 10.8 (1.4) degrees vs 3.9 (2.1)
      degrees ] in the distal compared with the proximal portion ( P<0.05 for all
      comparisons). There were significant correlations between DeltaNIR-O(2
      )saturation and Deltafascicle length ( r=-0.84, P<0.05), and between DeltaNIR
      O(2) saturation and Deltafascicle angle ( r=-0.90, P<0.05), between DeltaNIR
      blood volume and Deltafascicle length ( r=0.91, P<0.05), between DeltaNIR-blood
      volume and Deltafascicle angle ( r=-0.85, P<0.05). In conclusion, the plantar
      flexion exercise produced regional differences in oxygenation status consistent
      with regional differences in muscle architecture.

PMID- 14574578
TI  - Cerebral autoregulation is compromised during simulated fluctuations in
      gravitational stress.
AB  - Gravity places considerable stress on the cardiovascular system but cerebral
      autoregulation usually protects the cerebral blood vessels from fluctuations in
      blood pressure. However, in conditions such as those encountered on board a high
      performance aircraft, the gravitational stress is constantly changing and might
      compromise cerebral autoregulation. In this study we assessed the effect of
      oscillating orthostatic stress on cerebral autoregulation. Sixteen (eight male)
      healthy subjects [aged 27 (1) years] were exposed to steady-state lower body
      negative pressure (LBNP) at -15 and -40 mmHg and then to oscillating LBNP at the
      same pressures. The oscillatory LBNP was applied at 0.1 and 0.2 Hz. We made
      continuous recordings of RR-interval, blood pressure, cerebral blood flow
      velocity (CBFV), respiratory frequency and end-tidal CO(2). Oscillations in mean
      arterial pressure (MAP) and CBFV were assessed by autoregressive spectral
      analysis. Respiration was paced at 0.25 Hz to avoid interference from breathing.
      Steady-state LBNP at -40 mmHg significantly increased low-frequency (LF, 0.03
      0.14 Hz) powers of MAP ( P<0.01) but not of CBFV. Oscillatory 0.1 Hz LBNP (0 to 
      40 mmHg) significantly increased the LF power of MAP to a similar level as steady
      state LBNP but also resulted in a significant increase in the LF power of CBFV (
      P<0.01). Oscillatory LBNP at 0.2 Hz induced oscillations in MAP and CBFV at 0.2
      Hz. Cross-spectral analysis showed that the transfer of LBNP-induced oscillations
      in MAP onto the CBFV was significantly greater at 0.2 Hz than at 0.1 Hz (
      P<0.01). These results show that the ability of the cerebral vessels to modulate
      fluctuations in blood pressure is compromised during oscillatory compared with
      constant gravitational stress. Furthermore, this effect seems to be more
      pronounced at higher frequencies of oscillatory stress.

PMID- 14574579
TI  - Short-term creatine supplementation does not improve muscle activation or sprint
      performance in humans.
AB  - The purpose of this study was to examine the influence of short-term creatine
      (Cr) supplementation on exercise-induced transverse relaxation time (T2) and
      sprint performance during maximum intermittent cycling exercise using the muscle
      functional magnetic resonance imaging (mfMRI) technique. Twelve men were divided
      into a Cr supplementation group [the Cr group, taking 4 x (5 g Cr monohydrate +
      2.5 g maltodextrin)/day], or a placebo supplementation group (the P group, taking
      4 x 7.5 g maltodextrin/day). The allocation to the groups was based on cycling
      tests and the subject's physical characteristics, and thus was not randomized. A
      double-blind research design was employed for a 5-day supplementation period.
      mfMR images of the right thigh were collected at rest and immediately after two,
      five, and ten 6-s sprint bouts of maximum intermittent cycling exercise with a 30
      s recovery interval between sets. Before and after supplementation, blood was
      taken to calculate lactate accumulation, and the muscle volume of the thigh was
      determined by MRI. Following supplementation, there was significant body mass
      gain in the Cr group ( P<0.05), whereas the P group did not change. The exercise
      induced T2, blood lactate levels and sprint performance were not affected by Cr
      supplementation in any sprint bouts. These results suggest that short-term Cr
      supplementation does not influence short duration repetitive sprint performance
      and muscle activation and/or metabolic state during sprint cycling evaluated by
      mfMRI of the skeletal muscle in humans.

PMID- 14574580
TI  - Cellular localization of orexins in human anterior pituitary.
AB  - Orexins A and B are hypothalamic peptides derived from a precursor called prepro
      orexin and are associated with the stimulation of food intake and arousal. There
      is evidence that orexins act on some pituitary functions. Since no studies have
      been done concerning the presence of orexins in human pituitary, it is unclear
      whether the local effect of these peptides is due to orexins synthesized in the
      pituitary or to circulating-derived orexins. To define a possible paracrine
      regulatory role of orexins on pituitary cell function, we have sought to
      characterize the expression of orexins in the human adenohypophysis as well as to
      identify the cell types that express these proteins. In the present study, we
      used immunohistochemistry and double labeling to detect the presence of orexin A
      and orexin B in human pituitary. Orexin A was localized in 33% of pituitary
      cells. With double immunofluorescence techniques we demonstrated that orexin A is
      present in PRL (82 +/- 5.3%), TSH (18 +/- 2.3%), GH (10 +/- 2.3%), FSH (8 +/-
      2.6%), and LH (7 +/- 3.2%) cells, but not in corticotroph cells. Orexin B was
      found in virtually all corticotrophs cells of the anterior pituitary. These
      results demonstrate that lactotroph cells are the main source of orexin A and
      corticotroph cells of orexin B. In summary the present findings provide the first
      evidence that orexins A and B are expressed in specific human pituitary cell
      types. Our data provide the cellular basis for a paracrine role of orexins in
      human pituitary cell function and further our understanding regarding the
      mechanisms by which orexins influence neuroendocrine function.

PMID- 14574581
TI  - Gelsolin gene expression is upregulated in damaged rat and human livers within
      non-parenchymal cells and not in hepatocytes.
AB  - Gelsolin, a 90-kDa protein, was suggested to be involved in cell motility, to
      inhibit apoptosis and to have a protective role for tissue. This study intends to
      analyse the modulation of cytoplasmic gelsolin expression in damaged rat and
      human livers and to identify its cellular sources. In the normal liver gelsolin
      immunoreactive cells could be identified along vessel walls and along the
      sinusoids. In cultured rat hepatic stellate cells (HSCs), liver myofibroblasts
      (MFs), mononuclear cells (MCs) and sinusoidal endothelial cells (SECs), but not
      in hepatocytes, gelsolin expression could be detected by immunostaining and
      Northern blot analysis. In acute CCl4-induced liver damage there was no gelsolin
      positivity detectable in necrotic areas. However, in human fulminant hepatic
      failure positivity in the necrotic areas was detected. In chronically damaged rat
      and human livers gelsolin-immunoreactive cells could be identified within the
      fibrotic septa. Northern blot analysis revealed an increase of the gelsolin
      specific transcript level under conditions of acute and chronic human or rat
      liver damage. The amount of gelsolin-specific transcripts in SECs and large MCs
      isolated from damaged rat livers increased in comparison to cells obtained from
      normal rats. However, the amount of gelsolin-specific transcripts in small MCs
      (representing recruited inflammatory cells) decreased. In conclusion, SECs, MCs,
      MFs and HSCs, but not hepatocytes, express gelsolin. In the damaged liver all
      tested cell populations but the inflammatory cells and the hepatocytes are
      responsible for the enhanced gelsolin expression.

PMID- 14574582
TI  - Protein 4.1B in mouse islets of Langerhans and beta-cell tumorigenesis.
AB  - Protein 4.1 family proteins are thought to interact with membrane proteins and
      membrane skeletons. Immunohistochemical studies by light and electron microscopy
      were performed on mouse pancreas with a specific antibody against protein 4.1B.
      Specific protein 4.1B immunolabeling was observed on endocrine cells in the
      islets of Langerhans. Protein 4.1B localized along the plasma membranes facing
      adjacent cells. By immunoelectron microscopy, the immunolabeling of the cells was
      restricted to the cytoplasmic side just beneath their plasma membrane, including
      the membranes adjacent to neighboring cells, while the plasma membranes facing
      endothelial cells were not immunolabeled for protein 4.1B. The immunolocalization
      of E-cadherin was similar, if not identical, to that of protein 4.1B supporting
      the idea that protein 4.1B may be functionally interconnected with adhesion
      molecules. In a transgenic mouse model of pancreatic beta-cell carcinogenesis
      (Rip1Tag2), the loss of protein 4.1B expression coincided with the phenotypic
      transition from adenoma to carcinoma. Therefore, we propose a role of protein
      4.1B as a connecting and/or signaling molecule between membrane architecture,
      cell adhesion, and tumor cell invasion in mouse pancreatic endocrine cells.

PMID- 14574583
TI  - Temporal and spatial assembly of lipid droplet-associated proteins in 3T3-L1
      preadipocytes.
AB  - This study aimed to investigate the relationship between newly formed lipid
      droplets and lipid droplet surface proteins, including perilipin, adipose
      differentiation related protein (ADRP), and p200 kDa protein (p200) in 3T3-L1
      preadipocytes, during lipogenesis. Sterol ester was used to induce nascent lipid
      droplets in 3T3-L1 preadipocytes and the sequence of lipids and lipid droplet
      surface proteins was studied using a combination of immunohistochemistry and Nile
      red staining/Oil red O. We demonstrated that, although most growing lipid
      droplets appeared to have a lipid core surrounded by a fluorescent rim of ADRP,
      perilipin, and p200, tiny protein aggregates of ADRP, perilipin, or p200 could
      also be found to occur in the absence of lipid accumulation. In addition, ADRP
      associated with nascent lipid droplets prior to that of perilipin or p200. We
      provide evidence that lipid droplet surface proteins, especially ADRP and
      perilipin, are important in serving as a nucleation center for the assembly of
      lipid to form nascent lipid droplets.

PMID- 14574584
TI  - Immunohistochemical localization of macrophage migration inhibitory factor (MIF)
      in human gingival tissue and its pathophysiological functions.
AB  - Recent reports have indicated that macrophage migration inhibitory factor (MIF)
      plays a key role in systemic as well as local inflammatory and immune responses.
      In this study, the presence and localization of MIF in human gingival tissue were
      examined. The expression of MIF was confirmed by western blot analysis, which
      demonstrated the same band at 12.5 kDa in different gingival tissues.
      Immunohistochemical studies showed that MIF protein existed in the cytoplasm of
      keratinocytes, especially in free gingival epithelium and junctional epithelium.
      It was also found in basal cells, fibroblasts, and various cells. These cells
      were considered to be stimulated mechanically at all times. To determine the
      effect of mechanical stimuli, Gin-1 cells were cyclically stretched for a short
      time by using a Flexercell Strain Unit. RT-PCR analysis demonstrated upregulation
      of MIF mRNA in these Gin-1 cells. In this study, MIF existed not only in
      inflammatory parts but also in those areas with high cell proliferative activity
      subjected to external stimulus. Moreover, the finding that MIF protein levels of
      the control determined by immunohistochemical detection were quite similar to
      those for grown and stretched Gin-1 cells suggested that MIF protein was stored
      in the cytoplasm for some time and that MIF is an important autocrine mediator of
      homeostatic-dependent signaling events. These results suggest that MIF plays an
      important role in the homeostatic process of periodontal inflammation.

PMID- 14574585
TI  - Distribution of SERCA isoforms in human intrafusal fibers.
AB  - The sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) is a membrane protein that
      plays a crucial role in muscle relaxation by transporting cytosolic Ca2+ into the
      lumen of the sarco/endoplasmic reticulum. In this study, the presence of SERCA1
      and SERCA2 was investigated in human intrafusal fibers by immunocytochemistry.
      Nuclear bag1 fibers contained both SERCA1 and SERCA2 isoforms, with predominant
      staining seen with SERCA2 in the A and B regions. Most nuclear bag2 fibers also
      contained SERCA1 and SERCA2 isoforms and their coexistence frequently occurred in
      the A region. SERCA1 was present whereas SERCA2 was generally absent in the
      nuclear chain fibers. The staining intensity seen with the SERCA1 monoclonal
      antibody varied in the order of chain>bag1>bag2. The expression of SERCA1 isoform
      was found to correlate with the presence of fast myosin heavy chain (MyHC)
      isoform in nuclear chain fibers, whereas for nuclear bag fibers there was no such
      apparent correlation between patterns of expression of SERCA and MyHC isoforms.
      The phenotype revealed for the human bag fibers was very sophisticated and
      adapted to attain a very wide range of contraction and relaxation velocities.

PMID- 14574586
TI  - Smoothelin-positive cells in human and porcine semilunar valves.
AB  - Our aim was to further characterize the interstitial cell phenotypes of normal
      porcine and human semilunar valves, information necessary for the design of
      bioengineered valves and for the understanding of valve disease processes such as
      aortic valve sclerosis. Existence of fibroblasts, myofibroblasts, and smooth
      muscle-like cells within semilunar heart valves has been established. However,
      the nature of the smooth muscle cell population has been controversial. We used
      immunochemical and western blotting methods to determine the status of smoothelin
      and smooth muscle alpha-actin in the valve. Our examination of valve interstitial
      cells confirmed the presence of terminally differentiated, contractile smooth
      muscle cells in situ. They were arranged in small bundles of 5-35 cells within
      the ventricularis or as individual cells scattered throughout the valvular layers
      in vivo, and were present in cells explanted from the valves in vitro.
      Colocalization of these proteins in semilunar heart valves was achieved with
      double-labeling experiments. Protein extraction, followed by
      coimmunoprecipitation, electrophoresis, and western blotting confirmed the
      immunochemical analysis and suggested that smooth muscle alpha-actin and
      smoothelin interact, as has been previously postulated. The presence of
      contractile smooth muscle within the valve may be an important factor in
      understanding valve pathology and in the design of tissue engineering efforts.

PMID- 14574587
TI  - Mitochondrial localization of reactive oxygen species by dihydrofluorescein
      probes.
AB  - Mitochondria are the main source of reactive oxygen species (ROS). The aim of
      this work was to verify the ROS generation in situ in HeLa cells exposed to
      prooxidants and antioxidants (menadione, tert-butyl hydroperoxide, antimycin A,
      vitamin E, N-acetyl-L-cysteine, and butylated hydroxytoluene) using the ROS
      sensitive probes 6-carboxy-2',7'-dichlorodihydrofluorescein diacetate di
      acetomethyl ester (DCDHF) and dihydrofluorescein diacetate (DHF). Mitochondria
      were counterstained with the potential-sensitive probe tetramethylrhodamine
      methyl ester perchlorate (TMRM). Both DCDHF and DHF were able to detect the
      presence of ROS in mitochondria, though with distinct morphological features.
      DCDHF fluorescence was invariably blurred, smudged, and spread over the cytoplasm
      surrounding the major mitochondrial clusters. On the contrary, DHF fluorescence
      was sharp and delineated thin filaments which corresponded in all details to TMRM
      stained mitochondria. These data suggest that DCDHF does not reach the
      mitochondrial matrix but is oxidized by ROS released by mitochondria in the
      cytosol. On the other hand, DHF enters mitochondria and reacts with ROS released
      in the matrix. Cytosolic (DCDHF+) ROS but not matrix (DHF+) ROS, were
      significantly decreased by vitamin E. N-acetyl-L-cysteine was effective in
      reducing DCDHF and DHF photooxidation in the medium, but was unable to reduce
      intracellular ROS. ROS generation was accompanied by partial mitochondrial
      depolarization.

PMID- 14574588
TI  - Transblot and cytochemical identification of avidin-interacting proteins in
      mitochondria of cultured cells.
AB  - Cell lysates prepared from 3T3-L1 cells were analyzed by western blotting using
      the avidin-biotin complex system and anti-Bax antibody. The antibody interacted
      with bands of proteins with estimated molecular weights of 120, 74, 72, and 25
      kDa. However, only the 25-kDa band was detected with the anti-Bax antibody when
      the direct immunoblotting method was used. Peroxidase-conjugated avidin
      interacted with the 120-, 74-, and 72-kDa bands. This interaction was not limited
      to 3T3-L1 cells, because peroxidase-avidin also interacted with these three
      proteins in MC3T3-E1, YROS, Saos-2, MG63, SCCKN, and SCCTF cells although the
      staining intensity was different in each cell type. Avidin-peroxidase also
      interacted with these three proteins in the mitochondria-containing fractions
      prepared from 3T3-L1 cells. FITC-streptavidin was also localized in mitochondria
      in the cultured cells. The localization of avidin/streptavidin-interacting
      proteins in mitochondria was confirmed by using double staining with FITC
      streptavidin and Mito-tracker.

PMID- 14574589
TI  - Heterogeneous expression of TASK-3 and TRAAK in rat paraganglionic cells.
AB  - In the present study, we investigated the immunohistochemical localization of the
      two-pore K+ channels, TASK-3 and TRAAK, in paraganglionic cells within the
      superior cervical ganglion, stellate ganglion, and aortic body in comparison with
      membrane channels in chief cells of the carotid body. TASK-3 immunoreactivity was
      observed in the paraganglionic cells in all tissues examined. TRAAK
      immunoreactivity was observed in the chief cells of the aortic body as well as
      these of the carotid body, but not in the paraganglionic cells in the sympathetic
      (superior cervical and stellate) ganglia. Our findings indicate that sympathetic
      paraganglionic cells and glossopharyngeal/vagal paraganglionic cells were
      different from each other in the expression patterns of TASK-3 and TRAAK to
      result in the different chemoreception properties of sympathetic paraganglionic
      cells from those of chief cells of the aortic and carotid bodies.

PMID- 14574591
TI  - The effects of protocol and test situation on maximal vs. submaximal cervical
      motion: medicolegal implications.
AB  - The objectives of this study were to examine the influence of the measurement
      protocol on the range and consistency of cervical motion (CM) in maximal vs.
      feigned limitation of CM, to explore some cognitive aspects of the feigning
      performance and to assess the effect of imagined pain vs. financial gain as a
      stimulus for the submaximal performance. The directions of flexion, extension,
      right and left rotation and right and left lateral flexion were measured in 26
      normal subjects. Four protocols were compared: performance of CM with eyes open
      vs. eyes closed and testing at either a repetitive (within direction) or random
      (among directions) order. In each direction three measurements were recorded.
      Subjects were initially asked to move the head maximally, they were then
      presented with a vignette describing a fictitious accident involving the neck and
      were told to feign CM limitation in order to achieve unlawful compensation. In
      the third part, subjects were instructed to limit CM due to an imagined severe
      pain applying the repetitive order-eyes open paradigm only. Maximal CM paradigms
      were associated with significantly larger range ( p=0.0000) and higher
      consistency ( p=0.0000) compared the feigning paradigms. The eyes open-repetitive
      order protocol best separated between maximal and feigned performance. It was
      also indicated that the majority of subjects used the sensation of tension in the
      neck region as a cue for feigning while attempting to be as consistent as
      possible. Compared to feigning motivated by financial gain, limitation due to
      imagined pain resulted in significantly greater CM reductions and lesser
      consistency. The findings suggest that while feigning of motion impairment is
      probably based on somato-sensory input, the preferred CM testing protocol should
      consist of within direction repetitive movements with eyes open.

PMID- 14574590
TI  - An easily automated, closed-tube forensic DNA extraction procedure using a
      thermostable proteinase.
AB  - Most standard procedures for extracting DNA from forensic substrates involve
      manipulations that expose the sample to potential contamination and which reduce
      yields. Furthermore, most methods require centrifugation and/or solvent
      extraction steps that render them difficult to automate. We describe a simple
      closed-tube DNA extraction procedure using a proteinase from the thermophilic
      Bacillus species EA1 that produces good DNA yields from a wide range of forensic
      substrates. The reaction is controlled by a temperature shift regime programmed
      into a thermal cycler and so eliminates the need for solvent extraction or column
      purification. The new method is ideally suited to forensic samples where exposure
      to extraneous contaminating DNA must be avoided. In addition, The simplicity of
      the procedure makes it suitable for automation.

PMID- 14574592
TI  - Complete detachment of an aortic valve prosthesis 10 years after implantation.
AB  - A 47-year-old male patient died unexpectedly 10 years after replacement of the
      aortic valve with a Carbomedics heart valve prosthesis required for post
      endocarditic valve stenosis. The man was in regular medical attendance by his
      general practitioner and in hospital. Clinical data and examinations did not
      suggest the reoccurrence of endocarditis. Three months before his death a
      haemolytic anaemia of unknown genesis was diagnosed. One afternoon, while lifting
      a heavy object, the man suffered acute chest pain and collapsed. Resuscitation
      failed and the patient died in hospital. Autopsy revealed the completely detached
      valve prosthesis within the ascending aorta. Histological examination confirmed a
      chronic endocarditis at the site of the valve implantation.

PMID- 14574593
TI  - One-stage revision surgery to treat hip infected nonunion after stabilization
      with a sliding compression screw.
AB  - INTRODUCTION: Extracapsular hip infected nonunion after stabilization with a
      sliding hip screw (SCS) is uncommon and a convincing treatment method has not yet
      been reported in the literature. PATIENTS AND METHODS: Thirteen consecutive
      patients who sustained such a disability were treated with removal of SCS, local
      radical debridement, vancomycin powder with or without gentamicin solution
      application, re-insertion of a new SCS, and autogenous cancellous bone grafting.
      Postoperatively, ambulation with regulated weight bearing was encouraged as early
      as possible. Infectious microorganisms in 76% (10/13) of the lesion sites were
      oxacillin-resistant staphylococcus aureus (ORSA). RESULTS: Twelve patients were
      followed-up for at least 2 years (range, 2~6 years; median, 4 years) and all
      nonunions healed. The union rate was 100% (12/12) with a median union period of 4
      months (range, 3~6 months). No wound infection recurred at the last follow-up.
      The satisfactory rate of hip function was 92% (11/12, P<0.001). CONCLUSIONS: We,
      therefore, recommend this surgical procedure to treat all patients with a similar
      disability because of its high success rate and low complication rate.

PMID- 14574594
TI  - Mechanical testing of small fracture implants for comparison of insertion and
      failure torques.
AB  - INTRODUCTION: Small fracture screws are among the most commonly used implants in
      the field of orthopedic surgery. The goal of this study was to compare the
      insertion and failure torques of three screw types: cortical, partially threaded
      cancellous, and fully threaded cancellous from three manufacturers: Zimmer,
      Richards, and Synthes. MATERIALS AND METHODS: Each type of screw was subjected to
      biomechanical tests to determine the insertion ( n=6/group) and failure (
      n=10/group) torques. RESULTS: Two-factor ANOVA tests were run to determine
      whether the insertion or failure torques were different for the different screw
      types and manufacturers. In the case of insertion torques, neither the screw nor
      the manufacturer had any significant effect. In the case of failure torque,
      significant differences were found based on both the screw type and the
      manufacturer, with the cortical screws manufactured by Zimmer being the
      strongest. Although there were strength differences, the most important
      comparison clinically is between the failure torque and the insertion torque of
      each screw. In all cases, the failure torques were approximately 20 times larger
      than the insertion torques, and therefore no failures should occur if only
      torsional loads are applied during insertion. This comparison shows that factors
      other than screw strength and manufacturing processes may be involved in cases of
      screw failure during insertion. CONCLUSION: All three screw types from all three
      manufacturers appear to be mechanically reliable, with the proper insertion to
      failure torque ratio. The surgeon's choice of implant should be based on other
      considerations.

PMID- 14574595
TI  - Traumatic labral avulsion from the stable rim: a constant pathology in displaced
      transverse acetabular fractures.
AB  - INTRODUCTION: During the treatment of a malunited transverse acetabular fracture,
      a hitherto undescribed extended avulsion of the labrum from the stable acetabular
      fragment was found. Based on the labral pathomorphology present in this case, the
      hypothesis was put forward that traumatic acetabular labral avulsions are a
      constant phenomenon in transverse acetabular fractures. PATIENTS AND METHODS:
      Fourteen patients underwent capsulotomy and/or surgical dislocation of the
      involved hip to facilitate open reduction and internal fixation of transverse
      acetabular fractures. RESULTS: In all cases, the labrum was partially or
      completely detached from the superior acetabular rim. In eight cases with bucket
      handle tears of the labrum from the stable superior fragment, the injured portion
      was resected back to normal margins. In one case the labrum was avulsed with an
      attached piece of bone and was repaired by screw fixation. Small separations of
      the labrum from the underlying acetabular rim occurred at the level of the
      fractures in five cases with minor displacement and received no treatment.
      CONCLUSION: With displaced transverse acetabular fractures, consideration should
      be given to opening the joint at the time of open reduction and internal fixation
      to look for associated intracapsular injuries. An avulsed portion of the labrum
      should be left if stable and undamaged. If unstable and damaged, it is probably
      better resected and if unstable but intact and/or attached to a bony fragment, it
      should be repaired.

PMID- 14574596
TI  - AO or Schatzker? How reliable is classification of tibial plateau fractures?
AB  - INTRODUCTION: We compare the intra- and interobserver reproducibility of
      classifications of tibial plateau fractures most commonly used in our clinical
      practice. These were the AO and Schatzker classifications. PATIENTS AND METHODS:
      Agreement was measured using kappa coefficients on the data obtained from three
      observers reviewing 30 fractures and these values were interpreted according to
      Landis and Koch. RESULTS: It was found that both classifications were
      substantially reliable with regards to intraobserver reliability but that the
      Schatzker system was only fairly reliable and the AO classification moderately
      reliable with regards to interobserver reliability. Breaking down the AO
      classification, with regards to intraobserver reliability, the AO group was
      substantially reliable and the type excellently reliable. For interobserver
      reliability, the AO group was moderately reliable while the AO type was
      substantially reliable. CONCLUSION: For tibial plateau fractures seen on plain x
      ray, the AO classification is more reliable between observers than the Schatzker
      classification.

PMID- 14574597
TI  - Articulated distraction of the hip joint in the treatment of benign aggressive
      tumors located around the hip joint.
AB  - INTRODUCTION: The proximal femur and acetabulum are frequent sites for benign
      active and aggressive lesions. The risk of pathologic fracture is great when a
      bone-destroying pathology involves an anatomic location such as the hip joint
      that undergoes profound mechanical loading. If the destruction involves a large
      area around the joint, secure fixation cannot be achieved with internal fixation
      implants. The study investigates use of articulated hip distraction to protect
      reconstructions performed for the treatment of benign active or aggressive tumors
      presenting with pathologic fracture. PATIENTS AND METHODS: Five patients with a
      pathologic fracture of the proximal, intracapsular femur or the acetabulum were
      operated on at the authors' institution between 1997 and 1999. Following
      histopathologic approval of a benign tumor, all lesions were curetted,
      chemocauterized, and grafted and osteosynthesis was performed. The reconstruction
      was protected with an articulated hip distraction external fixator. All patients
      were mobilized in the immediate postoperative period. RESULTS: The patients were
      kept in external fixators for an average of 19.8 weeks (range: 16-24). The
      fixator was removed when bony consolidation was observed in anteroposterior and
      lateral x-rays of the lesion. The patients were followed for an average of 47
      months (range: 38-56) after frame removal. None of the lesions recurred. At the
      last follow-up examination, all patients displayed an excellent function
      according to the Musculoskeletal Tumor Society Rating Scale. CONCLUSION:
      According to the authors' knowledge, this investigation is the first in the
      literature describing the use of articulated joint distraction in the treatment
      of benign active and aggressive lesions around the hip joint. The procedure
      adopts principles of joint distraction into bone tumor surgery.

PMID- 14574598
TI  - Relevance of primary reduction for the clinical outcome of femoral neck fractures
      treated with cancellous screws.
AB  - INTRODUCTION: Femoral head-preserving treatment for femoral neck fractures with
      cancellous screws is a method widely performed, but its success depends on the
      quality of primary reduction. The goal of our study was to evaluate the relevance
      of reduction quality on the clinical outcome. PATIENTS AND METHODS: We
      retrospectively analyzed the postoperative reduction result of 39 patients. The
      angular rotation and the inferior displacement of the proximal fracture fragment
      were digitally assessed from AP radiographs. The clinical outcome was recorded by
      a follow-up after a mean 5.5 years. RESULTS: Unsuccessful healing was observed in
      eight patients, femoral head necrosis in three patients, non-union in two
      patients, implant loosening in one patient, and posttraumatic arthritis in two
      patients, all resulting in the need for a total hip replacement. This clinical
      course was strongly associated with a primary reduction in varus position,
      whereas reduction in anatomic or valgus angulation had no negative effect on the
      clinical outcome. An inferior offset was no negative predictor for successful
      healing. CONCLUSION: We conclude that a non-anatomic reduction in varus
      angulation significantly increases the risk of healing failure and therefore
      should be avoided. Reduction in valgus position should be performed if secondary
      redislocation is imminent.

PMID- 14574599
TI  - Influence of a screw with a hinge on the pull-out force at the cranial end
      vertebra in ventral derotation spondylodesis (VDS).
AB  - INTRODUCTION: Pull-out of the cranial end-vertebra screw following a correction
      of a scoliosis with the VDS implant is a common complication, especially in the
      thoracic region. It requires an extension of the fusion length or at least
      reduces the outcome of the correction. MATERIALS AND METHODS: We therefore looked
      for a new approach to solve the problem of end-vertebra screw pull-out. It was
      postulated that the axial pull-out force at the end-vertebra screw is reduced by
      a screw with a hinge between the head and threaded part. The aim of our study was
      to calculate theoretically and then determine experimentally the screw pull-out
      force of regular and modified VDS screws with a hinge during lateral shifting of
      the screw heads in the frontal plane. RESULTS: The use of a modified end-vertebra
      screw with a hinge on the cranial end vertebra of the correction region changes
      the shape of the threaded rod between the last two screws. Theoretically
      estimated, this leads to a reduction of the pull-out force to one-fourth of the
      value for the original VDS screw. Experimentally, the mean pull-out force for the
      modified end-vertebra screw was 110+/-8.6 N in comparison with the original
      screw, where the pull-out force was 214+/-7.2 N. CONCLUSION: A reduction of screw
      pull-out can be expected when a screw with a hinge is used for the cranial end
      vertebra.

PMID- 14574600
TI  - Removal of lumbar instrumentation for the treatment of recurrent low back pain in
      the absence of pseudarthrosis.
AB  - INTRODUCTION: Removal of spine instrumentation for the treatment of recurrent low
      back pain remains controversial in the absence of pseudarthrosis and when no
      obvious pain generators are present. It is our practice to offer these patients
      surgical exploration and removal of instrumentation. MATERIALS AND METHODS: Forty
      five patients underwent an anterior and posterior lumbar spinal fusion. The
      removal of instrumentation was performed by the same surgeon and senior author of
      this paper (MRP). The reason for the revision surgery was recurrent low back and
      leg pain. All patients had a solid fusion based on a thorough surgical
      exploration of the fusion mass. Instrumentation was deemed either solid or loose
      at time of removal based on the purchase at the screw-bone interface. Final
      outcomes were determined using a functional and satisfactory questionnaire and
      compared between the two groups (Loose Instrumentation versus Solid
      Instrumentation). RESULTS: The majority of the patients in both groups would
      recommend the surgery to a family member (79% overall), would have the surgery
      again themselves (82%) and consider the surgery a success (77%). Pain was
      significantly decreased from pre-operatively to post-operatively and from pre
      operative to final follow-up in both groups. The group of patients with loose
      instrumentation were significantly more likely to have a successful outcome than
      the group without loose instrumentation. CONCLUSIONS: This study indicates that
      the removal of instrumentation in the absence of pseudarthrosis is beneficial in
      the relief of low back pain and leg pain symptoms. Increased success rates were
      noted in patients with loose instrumentation. However, this classification was
      based on inter-operative inspection. Further studies of the ability to diagnose
      and predict success prior to surgery needs to be done.

PMID- 14574601
TI  - Mid-term results and quantitative comparison of postoperative shoulder function
      in traumatic and non-traumatic rotator cuff tears.
AB  - INTRODUCTION: The objective of this study was to compare the postoperative range
      of motion (ROM) and patient satisfaction after surgical reconstruction of
      traumatic and non-traumatic rotator cuff tears. MATERIALS AND METHODS: The cases
      of 46 consecutive patients who underwent the same standardised surgical
      reconstruction and postoperative rehabilitation protocol between 1993 and 1998
      were reviewed. Traumatic (group I, n=20, average age 34.2 years, range 15-49
      years) and non-traumatic tears (group II, n=26, average age 54.1 years, range 50
      68 years) formed the two study groups. Mean follow-up lasted 47.1 months (range
      13-105 months) in group I and 41.4 months (range 11-94 months) in group II.
      Assessment included postoperative shoulder function with Constant and Murley's
      score and visual analogue scale (VAS). RESULTS: Significantly ( p=0.0019) better
      results were observed in group I with an average of 94.1 points for Constant's
      score, compared with 75.3 points in group II. Postoperative shoulder function was
      not affected regarding full-thickness or partial tears ( p=0.239) in group I. VAS
      revealed an excellent or good result in all patients of group I ( n=20) and 50%
      of group II ( n=13/26). Quantitative comparison of postoperative ROM demonstrated
      significantly better results in forward flexion ( p=0.013), abduction ( p=0.0019)
      and external rotation ( p=0.0042) for group I. The remaining postoperative
      external rotation deficit for group II with a loss of 31% compared with group I
      (38.9 degrees vs 56.6 degrees ) was statistically and clinically relevant.
      CONCLUSION: The results demonstrate that surgical reconstruction of traumatic and
      non-traumatic rotator cuff tears is a successful procedure. Comparison of both
      groups revealed significantly better postoperative results in the younger,
      traumatic collective.

PMID- 14574602
TI  - Recurrent aggressive chondrosarcoma of the middle phalanx of the index finger:
      excision and reconstruction with an osteocartilaginous allograft.
AB  - INTRODUCTION: Chondrosarcomas are malignant tumours and need to be treated
      aggressively including ablative surgery. Bovee et al. and Mankin have recently
      drawn attention to a less aggressive behaviour of chondrosarcomas of the
      phalanges compared with those of other localizations including the metacarpals.
      MATERIALS AND METHODS: An 12 year follow-up of a patient with a chondrosarcoma of
      the middle phalanx of the index finger is presented. The lesion was curetted
      initially, and a repeat curettage was performed 4 years later. Finally, 8 years
      later the phalanx was excised and reconstructed with an osteocartilaginous
      allograft. Histologically, the lesion changed from a chondrosarcoma grade I to
      grade II. RESULT: The patient continues to be free of recurrence and metastases 4
      years after the final resection. CONCLUSION: The potential for systemic disease
      of chondrosarcomas of the phalanges is probably much lower than in
      chondrosarcomas of other localizations, and therefore digit-sparing techniques
      may be considered rather than ablative procedures.

PMID- 14574603
TI  - Overwhelming septic infection with a multi-resistant Staphylococcus aureus (MRSA)
      after total knee replacement.
AB  - INTRODUCTION: The incidence of early deep infection after arthroplasty of the
      knee is very low but could represent a serious future problem. MATERIAL AND
      METHODS: The authors report on a 71-year-old woman with gonarthritis who was
      supplied with a total knee endoprosthesis and developed a local infection
      followed by septic shock. RESULTS: The infection was evidently caused by a
      multiresistant Staphylococcus aureus (Staph. aureus). The primary clinical signs
      closely resembled a necrotizing fasciitis. Systemic and local application of
      vancomycin led to an improvement of the symptoms at secondary sites, but only the
      amputation of the primarily infected leg was lifesaving. CONCLUSION: In order to
      prevent such events, the authors recommend a number of additional presurgical
      measures. Firstly, a swab from the nose and throat should be taken prior to an
      elective surgery in patients with elevated risk of immunodeficiency, for example
      in patients with diabetes. The diabetes should be adequately treated before an
      elective operation is undertaken. Secondly, an early punction of the knee joint
      should be carried out if there is any doubt regarding inflammation. Isolated
      infectious agents should be grounds for early revision, which should always be
      completed with a rinsing procedure and with adequate antibiotics. Immunotherapy
      should be taken into consideration. Antiepidemic measures are recommended in
      cases with known Staph. aureus.

PMID- 14574604
TI  - Benign noninfectious subcutaneous emphysema of the hand.
AB  - A 17-year-old girl presented pain and subcutaneous crepitation in the left hand.
      Because of lack of systemic symptoms, non-infectious cause was considered.
      Radiographic and magnetic resonance imaging revealed subcutaneous emphysema. A
      chest x-ray was reported as normal but chest computerised tomography revealed
      pneumomediastinum. On the third day of the hospitalisation, subcutaneous
      emphysema spread to arm, shoulder, head, left hemithorax, back, bilateral
      supraclavicular, cervical, submandibular and periorbital regions.
      Pneumomediastinum and subcutaneous emphysema disappeared during 6 weeks of follow
      up with conservative methods. This might have prevented unnecessary surgical
      intervention. This report demonstrates that benign non-infectious subcutaneous
      emphysema of the hand due to pneumomediastinum should be kept in mind in hand
      surgery.

PMID- 14574605
TI  - One case of gram-negative anaerobic spondylodiscitis with Prevotella intermedia.
AB  - We report the case of a 45-year-old woman with spondylodiscitis at L1/L2,
      communicating with paravertebral, intravertebral and bilateral psoas abscesses.
      Percutaneous computed tomography (CT)-guided abscess drainage and an intravenous
      antibiotic therapy with Imipenem were performed. After removing the drainage at 2
      weeks, the patient was discharged at 4 weeks with normalized blood parameters,
      normal temperature, and without need for analgesics. The underlying bacterium in
      the case was a very rare gram-negative anaerobic bacterium: Prevotella
      intermedia.

PMID- 14574606
TI  - Three cases of regional migratory osteoporosis.
AB  - We examined three patients with regional migratory osteoporosis. Radionucleotide
      bone scanning and MRI was helpful in the diagnosis of this disease, and all
      patients recovered with conservative treatment. A biopsy of the femoral head,
      which was performed in one case, demonstrated bone marrow edema without
      osteonecrosis. A low intensity area of subchondral bone was observed on a T1
      weighted image in two cases, as well as a fracture of the subchondral bone, which
      might be associated with transient osteoporosis. In one case, the affected region
      migrated from the medial femoral condyle to the lateral femoral condyle in the
      same knee joint.

PMID- 14574607
TI  - Property analysis of ectopic calcification in the carpal tunnel identification of
      apatite crystals: a case report.
AB  - INTRODUCTION: A 64-year-old woman presented with symptoms of subacute
      exacerbation of a year-long carpal tunnel syndrome that was caused by a large
      calcified mass in the tunnel. CONCLUSION: The resected mass consisted of very
      tiny rods, and x-ray diffraction analysis, as well as the component analysis
      using energy dispersive x-ray microanalysis, revealed the mass to be most
      compatible with apatite. The back-scattered electron images suggested that
      precipitation might be a mechanism for development of the calcified mass.

PMID- 14574608
TI  - Effects of ileum transplantation and chronic rejection on absorption and
      synthesis of cholesterol in pigs.
AB  - We investigated the effects of ileum allotransplantation and chronic graft
      rejection on the synthesis and absorption of cholesterol. Twenty pigs underwent
      intestinal transection or ileum transplantation, in which the distal half of the
      jejunoileum was replaced with an ileal autograft or allograft. Conventional
      triple therapy with cyclosporine (10 mg/kg per day), azathioprine and
      methylprednisolone was tapered to cyclosporine (5 mg/kg per day) after 10 weeks.
      Serum lathosterol and campesterol, respective markers of cholesterol synthesis
      and absorption, were determined and related to graft histology. When compared to
      transected controls, auto- and allotransplantation of ileum similarly increased (
      P<0.05) lathosterol and decreased ( P<0.01) campesterol for 12 weeks, despite
      normal graft histology. Chronic graft rejection progressed between 12 and 18
      weeks, when a further increase in lathosterol (+104%) and decrease in campesterol
      (-67%) was observed. Obliteration of mesenterial arteries in chronically
      rejecting grafts was associated with high cholesterol synthesis ( R=0.975,
      P=0.0512). Auto- and allotransplantation of the ileum similarly modulate
      synthesis and absorption of cholesterol in pigs with non-rejecting grafts.
      Chronic rejection of the ileal graft appears to markedly increase cholesterol
      synthesis, which may primarily result from impaired ileal reabsorption of bile
      acids due to gradual obliteration of mesenterial arteries (chronic rejection).
      Serial measurements of cholesterol synthesis and bile acid absorption may prove
      to be a useful tool in the diagnosis of chronic rejection-associated small
      intestinal graft dysfunction.

PMID- 14574609
TI  - Neonatal genital reconstruction in penile agenesis by anterior sagittal
      anorectovaginourethroplasty.
AB  - Penile agenesis is a rare anomaly, occurring once in every 30 million births.
      Early gender reassignment and genital reconstruction helps the family to accept
      the child's altered gender and to reduce psychological problems. In the past,
      multiple operations were carried out to form feminized external genitalia. This
      report describes a single-stage gender reassignment and genital reconstruction by
      anterior sagittal anorectovaginourethroplasty in a neonate with penile agenesis.

PMID- 14574610
TI  - Tunica vaginalis reinforcement flap in reoperative Snodgrass procedure.
AB  - Interposing vascularized flaps between urethra and skin sutures is recommended in
      hypospadias surgery to decrease the rate of urethrocutaneous fistula. For this
      purpose nine patients with failed results after at least one hypospadias surgery
      and with insufficient foreskin were included in the study. Tubularized incised
      plate uretroplasty and tunica vaginalis reinforcement flap were performed to all
      patients with normal urethral plate. After a mean follow-up of 8.9 months (range
      3-20) only one patient had developed a fistula. We believe that tunica vaginalis
      reinforcement flap decreases fistulas in reoperative hypospadias surgery in
      patients with insufficient foreskin or with a circumcised penis.

PMID- 14574611
TI  - Intraspinal extradural teratoma mimicking neural sheath tumor in infant.
AB  - INTRODUCTION: An intraspinal teratoma that is located entirely extradurally is
      unusual both in children and in adults. CASE HISTORY: The authors present a case
      of an 8-month-old male infant with an extradurally arising intraspinal mature
      teratoma located from T-2 to T-4, who had suffered from progressive paraparesis
      (grade 1). The patient did not have any stigmata or anomalies suggesting spinal
      dysraphism. Spinal MRI showed a cystic extradural mass markedly compressing the
      dural sac. On operation, the only way of getting sufficient space for exposure of
      the whole tumor was to perform hemilaminectomies with preservation of facetal
      areas to prevent postoperative instability. The tumor was well encapsulated and
      located entirely extradurally, and the cystic portion was occupied with yellowish
      fluid. The site of tumor occurrence was the spinal root sheath, mimicking a
      neural sheath tumor. Paraparesis had improved markedly to grade 4 by the time of
      the neurological examination 3 months after operation.

PMID- 14574612
TI  - Primary central nervous system sarcomas in children: clinical, radiological, and
      pathological features.
AB  - PATIENTS AND METHODS: The clinical, radiological, surgical, and pathological
      findings of 16 children with a primary central nervous system (CNS) sarcoma are
      reported. There were 8 (50%) girls and 8 (50%) boys ranging in age from 4 months
      to 14 years (mean age 4.8 years). Four patients (23%) were in their 1st year of
      life. Fourteen children (87%) had an intracranial sarcoma, and 2 (13%) had
      intraspinal tumors. Nine intracranial tumors (60%) were supratentorial. The
      parietal and temporal regions were the most frequently involved sites. RESULTS:
      Characteristic imaging findings included tumor cysts in 7 patients and marked
      tumoral enhancement in 9 (69%) with intratumoral calcification and hemorrhage.
      All patients underwent at least one operation to surgically remove the tumor with
      the aim of maximal resection and 3 patients underwent a second resection due to a
      recurrent tumor. Resection was total in 9 (53%) patients and subtotal in another
      7 (41%). Dural attachment by tumor was confirmed in 7 (44%) patients and
      parenchymal invasion was present in 9 (56%). In one-third of the patients there
      was a well-defined plane of dissection around the tumor. Postoperative radiation
      was used in 10 patients. Postoperative chemotherapy was used in all but 2
      patients. Immunohistochemical studies were available in 13 patients with the most
      consistent finding being strong vimentin positivity. Five out of the 6 patients
      in whom the proliferation markers were obtained demonstrated a high proliferation
      index (Ki-67 labeling index, 20-50%). The mean length of survival in the group
      was 4.6 years (range 1 month to 16 years). Children who presented in the 1st year
      of life had shorter survival than those who presented at an older age. Six
      patients (40%) had cerebrospinal fluid (CSF) dissemination of the tumor. CSF
      dissemination was associated with a shorter mean survival of 1.9 years.
      CONCLUSIONS: Our review of this series of patients indicates the requirement for
      adjuvant therapy and for continued efforts to classify tumor subtypes aimed at
      optimizing future treatments for patients with a primary CNS sarcoma.

PMID- 14574613
TI  - Molecular and enzymatic properties of a cathepsin L-like proteinase with distinct
      substrate specificity from northern shrimp (Pandalus borealis).
AB  - We purified a cathepsin L-like proteinase to homogeneity from the hepatopancreas
      of northern shrimp Pandalus borealis by several chromatographic procedures. The
      purified proteinase showed the highest specificity for leucine residue at P2, a
      specificity pattern similar to cathepsins S and K whereas proline and arginine
      residues were not suitable as P2 substrates. However, unlike these proteinases,
      it accepted valine almost equally to the phenylalanine residue at P2. The shrimp
      cathepsin was strongly inhibited by E-64, leupeptin and antipain, while
      benzyloxycarbonyl-Phe-Tyr(t-Bu)-CHN2, a specific inhibitor of cathepsin L,
      remained largely ineffective. Next, we determined the primary structure of the
      shrimp enzyme by molecular cloning and investigated the residues constituting the
      S2 subsite, which is possibly involved in its unusual substrate specificity. The
      deduced amino acid sequence of the shrimp proteinase shared the highest identity
      of 65% with a cathepsin L-like proteinase from lobster, but its identity to the
      well-characterized mammalian cathepsins S, L, and K fell within narrower ranges
      of 52-55%. However, the shrimp proteinase differed from these cathepsins in some
      key residues including, for example, the unique occurrence of cysteine and
      glutamine residues at the structurally important S2 subsite. Interestingly,
      transcripts of this proteinase were exclusively detected in the shrimp gut
      coinciding with its broad pH activity and stability profiles, which is also
      unusual as a cysteine proteinase. These results suggest that the shrimp enzyme is
      homologous to mammalian cathepsins S, L, and K, but is distinct from each of
      these proteinases in both enzymatic and structural properties.

PMID- 14574616
TI  - Impaired recovery of CD4+ cell counts following highly active antiretroviral
      therapy in drug-naive patients coinfected with human immunodeficiency virus and
      hepatitis C virus.
AB  - Coinfection with the human immunodeficiency virus (HIV) and the hepatitis C virus
      (HCV) is highly prevalent in southern Europe. However, there are few and
      contradictory data about the effect of HCV carriage on the response to highly
      active antiretroviral therapy (HAART). In this study, the recovery of CD4+ T
      cells following HAART among antiretroviral-naive patients seropositive for HIV
      with and without HCV coinfection was investigated. Two hundred one HIV-infected
      patients without previous exposure to antiretroviral drugs were included in the
      study. HCV coinfection was detected in 123 (61%) patients. The time to recover
      200 CD4+ cells/ microl was longer in the HCV-positive group ( P<0.001). In a Cox
      model, HCV infection and lack of persistent HIV viremia (defined as <200
      copies/ml) were associated with the time to recover 200 CD4+ cells/ microl. The
      mean increase in CD4+ cell counts was lower in the HCV-positive group during the
      first year of therapy. HIV/HCV-coinfected patients naive for antiretroviral
      therapy show a delayed recovery of CD4+ cell counts after starting HAART.

PMID- 14574617
TI  - Comments on the failure to detect Chlamydia pneumoniae in atherosclerosis.

PMID- 14574615
TI  - RNA polymerase II transcription apparatus in Schizosaccharomyces pombe.
AB  - Eukaryotic RNA polymerase II (Pol II) transcription apparatus is a multi-protein
      complex consisting of the RNA polymerase II core enzyme (12 subunits), general
      transcription factors, the mediator, and some other specific accessory factors
      with regulatory functions. After genome sequencing was completed, the fission
      yeast Schizosaccharomyces pombe was recognized as a good model organism to study
      the Pol II transcription apparatus, because most genetic methods developed with
      the budding yeast Saccharomyces cerevisiae are applicable but the genetic systems
      of Sch. pombe, including transcription, are closer to those in higher eukaryotes.
      Recent studies on components of the Sch. pombe basal transcription machinery not
      only revealed a number of properties common in other eukaryotes but also
      illuminated some features unique to Sch. pombe. Convergence of information from
      both yeasts will provide us with a more general understanding of eukaryotic
      transcription.

PMID- 14574618
TI  - Comparison of a commercial reversed passive latex agglutination assay to an
      enzyme immunoassay for the detection of Shiga toxin-producing Escherichia coli.
AB  - A multicenter study was performed to compare the performance of a prototypic
      reversed passive latex agglutination assay (VTEC Screen "Seiken"; Denka-Seiken,
      Japan) with the Premier EHEC Enzyme Immunoassay (Meridian Diagnostics, USA) for
      the detection of Shiga toxin in 554 diarrheal stool samples. Standard culture on
      sorbitol MacConkey agar and the use of latex agglutination reagents were included
      to identify the Escherichia coli O157, O26 and O111 serotypes. There was 99%
      agreement between the VTEC screen and enzyme immunoassay (kappa=0.823). Seventeen
      samples were positive for toxin by one or both assays. One toxin-positive sample
      using the enzyme immunoassay and four positive samples using the VTEC Screen
      could not be confirmed. Serotypes identified included: O157:H7 (n=8), O26 (n=2),
      O111 (n=1) and O45:H2 (n=1). The VTEC screen is easy to perform and comparable to
      the Meridian EHEC test for detection of Shiga toxin in clinical samples.

PMID- 14574619
TI  - Responses of mycorrhizal and non-mycorrhizal Erica cinerea and Vaccinium
      macrocarpon to Glomus mosseae.
AB  - An investigation was carried out on the mycorrhizal colonisation, growth and
      nutrition of two members of the Ericaceae in close proximity to an arbuscular
      mycorrhizal (AM) association. This was undertaken by separating mycorrhizal (EM)
      and non-mycorrhizal (NEM) Erica cinerea and Vaccinium macrocarpon from AM
      (inoculated by Glomus mosseae) and non-mycorrhizal (NAM) Plantago lanceolata
      using a 30 micro m nylon mesh in a sand culture/pot system. Ericoid mycorrhizal
      colonisation by Hymenoscyphus ericae on root systems of E. cinerea and V.
      macrocarpon was in the range 14-22% and 58-69%, respectively. The presence of AM
      P. lanceolata had no effect on the ericoid mycorrhizal colonisation of E. cinerea
      and V. macrocarpon. NEM E. cinerea showed reductions in shoot biomass and shoot
      nitrogen concentrations after exposure to AM P. lanceolata after incubations of 6
      and 9 weeks but there were no differences in dry mass, length, and nitrogen and
      phosphorus concentrations of the root systems between the treatment combinations.
      Reductions were also found, after incubations of 6 and 9 weeks, in shoot dry
      mass, leaf area and shoot nitrogen concentrations of NEM V. macrocarpon in the
      presence of AM P. lanceolata but no changes occurred in the length and dry mass
      of the root systems. There were no differences in maximum photosynthesis in V.
      macrocarpon between treatment combinations but NEM V. macrocarpon in the presence
      of AM P. lanceolata had the lowest transpiration rates and stomatal conductance
      and the highest nitrogen- and phosphorus-use efficiencies compared with the other
      treatment combinations. These results are discussed in relation to the type of
      interaction found in these compatible and incompatible mycorrhizal associations.

PMID- 14574620
TI  - Mycorrhizal inoculant alleviates salt stress in Sesbania aegyptiaca and Sesbania
      grandiflora under field conditions: evidence for reduced sodium and improved
      magnesium uptake.
AB  - A field experiment was conducted to examine the effect of the arbuscular
      mycorrhizal fungus Glomus macrocarpum and salinity on growth of Sesbania
      aegyptiaca and S. grandiflora. In the salt-stressed soil, mycorrhizal root
      colonisation and sporulation was significantly higher in AM-inoculated than in
      uninoculated plants. Mycorrhizal seedlings had significantly higher root and
      shoot dry biomass production than non-mycorrhizal seedlings grown in saline soil.
      The content of chlorophyll was greater in the leaves of mycorrhiza-inoculated as
      compared to uninoculated seedlings. The number of nodules was significantly
      higher in mycorrhizal than non-mycorrhizal plants. Mycorrhizal seedling tissue
      had significantly increased concentrations of P, N and Mg but lower Na
      concentration than non-mycorrhizal seedlings. Under salinity stress conditions
      both Sesbania sp. showed a high degree of dependence on mycorrhizae, increasing
      with the age of the plants. The reduction in Na uptake together with a
      concomitant increase in P, N and Mg absorption and high chlorophyll content in
      mycorrhizal plants may be important salt-alleviating mechanisms for plants
      growing in saline soil.

PMID- 14574622
TI  - 24S-hydroxycholesterol: a marker of brain cholesterol metabolism.
AB  - The enzymatic conversion of CNS cholesterol to 24S-hydroxycholesterol, which
      readily crosses the blood-brain barrier, is the major pathway for brain
      cholesterol elimination and brain cholesterol homeostasis maintenance. The enzyme
      mediating this conversion has been characterized at the molecular level (CYP46)
      and is mainly located in neurons. Like other oxysterols, 24S-hydroxycholesterol
      is efficiently converted into normal bile acids or excreted in bile in its
      sulfated and glucuronidated form. Levels of 24S-hydroxycholesterol in the
      circulation decrease with age in infants and children. In adults, however, the
      levels appear to be stable. There is accumulating evidence pointing toward a
      potentially important link between cholesterol, beta-amyloid, and Alzheimer's
      disease. Concentrations of 24S-hydroxycholesterol in plasma and cerebrospinal
      fluid (CSF) are significantly higher in Alzheimer's disease and vascular demented
      patients at early stages of the disease compared to healthy subjects. Variations
      in genetic background, time of disease onset, and severity of dementia are
      potential sources of variance. Inhibitors of cholesterol biosynthesis, also
      termed statins, seem to have a reductive influence on the generation of the
      amyloid precursor protein, the neuronal secretion of beta-amyloid, and on de novo
      cholesterol synthesis. Recent epidemiological studies indicate that the
      prevalence of diagnosed AD and vascular dementia is reduced among people taking
      statins for a longer period of time. High-dose simvastatin treatment (80 mg/day)
      in patients with hypercholesterolemia leads to a significant decrease in brain
      specific serum 24S-hydroxycholesterol concentrations and indicates a diminished
      cholesterol metabolism in the brain. CSF levels of cholesterol and lathosterol, a
      cholesterol precursor considered to be an indicator for cholesterol neogenesis,
      were significantly decreased in statin-treated subjects compared to non-treated
      normo- and hypercholesterolemic subjects. Also, CSF concentrations of 24S
      hydroxycholesterol were significantly lower in statin-treated patients compared
      to normocholesterolemic subjects. Treatment with high-dose simvastatin in
      normocholesterolemic Alzheimer patients for 26 weeks at early stages of the
      disease results in a significant decrease in Abeta-levels in cerebrospinal fluid.
      This decrease correlates with the reduction of 24S-hydroxycholesterol.

PMID- 14574621
TI  - Changes in psychological distress of women in long-term remission from breast
      cancer in two different geographical settings: a randomized study.
AB  - GOALS OF WORK: Psychological distress and coping styles in women diagnosed with
      stages I and II breast cancer have attracted substantial clinical and research
      attention over the last several decades. The contradictory and, at times,
      controversial findings stimulated the present randomized research whose purpose
      was to explore the possibility and probability of predicting which variables
      affect the psychological distress level of women with breast cancer 1 to 5 years
      after diagnosis (time period 1) and 6 to 8 months after period 1 (time period 2).
      PATIENTS AND METHODS: The study was conducted in two large oncology centers in
      Graz, Austria, and Jerusalem, Israel, with a sample population comprising 424
      patients. MAIN RESULTS: The only variables that significantly predicted change in
      the psychological distress levels (Grand Severity Index, GSI; except for the GSI
      level during period 1) were Fighting Spirit (Mental Adjustment to Cancer, MAC) in
      the Graz sample and Perceived Family Support (PFS) in the Jerusalem sample. These
      results are discussed in relation to other findings. CONCLUSIONS: In light of
      these findings, it is highly important to preliminarily identify women with less
      adaptive psychological coping mechanisms and to provide them with efficacy tools
      for behavioral and cognitive changes within their own network of social and
      health resources.

PMID- 14574623
TI  - Cholesterol, synaptic function and Alzheimer's disease.
AB  - We experimentally modeled neuronal cholesterol imbalance by creating an acute
      biochemical increase in cholesterol turnover in rat hippocampal slices. This kind
      of experimental set-up impairs the redistribution of cholesterol from one cell to
      another via lipoprotein transport. While increasing cholesterol removal or
      immediately afterwards, we evoked and recorded two brain waveforms, paired pulse
      facilitation (PPF) and long-term potentiation (LTP), which indicate
      neurotransmission and synaptic plasticity, respectively. We found that the lack
      of cholesterol supply to neurons impaired both PPF and LTP. From additional
      immunofluorescent analysis of the slices, we could demonstrate that the
      cholesterol imbalance also caused neurodegeneration of hippocampal neural cell
      processes and the appearance of tau protein pathology in the mossy fibers. We
      also analyzed rats fed a cholesterol diet and discovered that they had increased
      hippocampal cholesterol biosynthesis and impaired LTP. Cholesterol-fed rats were
      also characterized by Alzheimer's-like brain amyloid that we did not observe in
      the model of acute cholesterol imbalance. Our data and research by others suggest
      that biological cholesterol homeostasis dysregulation itself plays a key role in
      synaptic plasticity impairment and neuronal degeneration, and is the primary
      cause for several Alzheimer's disease hallmarks not limited to brain amyloids.
      Moreover, changes in the neurochemistry of amyloid beta, tau, neuronal
      cytoskeleton, and oxidative stress reactions due to Alzheimer's likely represent
      physiological transitory mechanisms that aim to compensate impaired brain
      cholesterol dynamics and/or associated neurotransmission and synaptic plasticity
      failure. Part of this article was published as netprint and is available under
      the URL http://clinmed.netprints.org/cgi/content/full/2001100005v1.

PMID- 14574624
TI  - Brain cholesterol, statins and Alzheimer's Disease.
AB  - Growing evidence suggests that cellular cholesterol homeostasis is causally
      involved in different steps leading to pathological events in the brain of
      Alzheimer's Disease (AD) patients. It was previously demonstrated that the
      processing of the amyloid beta-peptide precursor protein (APP) is modulated by
      pronounced alterations in cellular cholesterol levels using statins or
      cholesterol extracting agents. However, a cholesterol-rich diet was found to
      enhance amyloid beta-peptide (Abeta) burden in the brain of transgenic mice
      without clearly affecting total brain cholesterol levels. Recent retrospective
      epidemiological studies have reported that the use of statins potentially
      suppresses the development of AD. Although some HMG-CoA reductase inhibitors seem
      to influence the central cholesterol pool in vivo, the above epidemiological
      findings are probably not linked to statin-induced changes in brain membrane
      cholesterol levels per se since not all statins active in preventing AD enter the
      central nervous system (CNS). Recently, we reported that different statins,
      regardless of their brain availability, induce alterations in cellular
      cholesterol distribution in the brain. Such pleiotropic, cholesterol-synthesis
      independent statin effects might be indirect and are possibly mediated at the
      blood-brain barrier (BBB) via nitric oxide (NO) or apolipoprotein E (ApoE).

PMID- 14574626
TI  - Cholesterol and Abeta aggregation.
AB  - Regarding deposition of amyloid beta-protein (Abeta) in brains with Alzheimer's
      disease (AD), we previously identified a novel Abeta species that strongly binds
      to GM1 ganglioside (GM1) in human brains that exhibit early pathological changes
      of AD. We hypothesized that Abeta undergoes conformational alteration through its
      binding to GM1 and acts as a seed. We recently found that an increase in the
      cholesterol concentration in host membranes markedly accelerates Abeta binding to
      GM1. We then investigated whether the cholesterol concentration in neuronal
      membranes could be altered under biological conditions that are associated with
      risk factors for AD development. We attempted to determine the distribution of
      cholesterol in the synaptic plasma membranes (SPMs) of human apolipoprotein E
      (apoE)-knock-in mice and found that the cholesterol concentration in the
      exofacial leaflet of SPMs of the human apoE4-knock-in mice was approximately
      twice that of human apoE3-knock-in mice. The results of our studies suggest that
      an increase in the cholesterol concentration in the neuronal membranes
      accelerates Abeta aggregation through the formation of an endogenous seed.

PMID- 14574625
TI  - Cholesterol and tau protein--findings in Alzheimer's and Niemann Pick C's
      disease.
AB  - Niemann Pick C (NPC), a fatal autosomal-recessive neurovisceral lipid storage
      disorder, is a juvenile dementia with massive nerve-cell loss and cytoskeletal
      abnormalities in cerebral neurons. These abnormalities consist of tangles of tau
      protein, which is otherwise highly soluble and usually stabilizes the
      microtubules. Immunologically and ultrastructurally similar tangles are seen some
      decades later in patients with Alzheimer's disease (AD). There is evidence that
      tangle-bearing cells in both diseases show higher levels of free (i. e. filipin
      positive) cholesterol than adjacent tangle-free nerve cells. The cholesterol
      accumulates either in a more diffuse way (mainly in AD) or in granule-like
      accumulations (mainly in NPC). In NPC, neuron cholesterol may originate from
      sources other than the alimentary tract. Experiments with a NPC mouse model
      revealed that even in pure neuron cultures, the NPC -/- neurons accumulate free
      cholesterol in contrast to NPC-wt littermates, suggesting that the cholesterol is
      either synthesized by the neurons or liberated from degenerated ones before being
      taken up by the endosomal/lysosomal pathway. The accumulation of free cholesterol
      in the somata of NPC neurons is associated with a decrease of cholesterol levels
      in myelin sheaths. In terms of tau protein, NPC -/- mice exhibit higher levels of
      AT8-positive tau, suggesting that the phosphorylation-dependent mAb AT8 has
      detected a tau-epitope in a state considered to represent early stages of tangle
      formation. Concomitantly to the increase in free intracellular cholesterol, the
      rate-limiting enzyme in cholesterol and isoprenoid biosynthesis, HMG-CoA
      reductase, was found to be significantly reduced. Experimental blockade of the
      enzyme's activity by application of the lipid-lowering drug lovastatin showed
      subcellular shifts in tau phosphorylation as monitored with mAbs AT8, 12E8 and
      others. In summary, the data showed interesting similarities between NPC and AD
      suggesting some pathological metabolic pathway in common.

PMID- 14574627
TI  - Cholesterol, a modulator of membrane-associated Abeta-fibrillogenesis.
AB  - One of the major pathological features of Alzheimer's disease is the presence of
      extracellular amyloid plaques that are predominantly composed of the amyloid-beta
      peptide (Abeta). Characterisation of plaques demonstrated the predominance of two
      peptides differing at the carboxyl terminus by 2 hydrophobic amino acids, Abeta40
      and Abeta42. Diffuse plaques associated with AD are composed predominantly of
      Abeta42, whereas senile plaques contain both Abeta40 and Abeta42. Recently, it
      has been suggested that diffuse plaque formation is initiated as a plasma
      membrane bound Abeta species and that Abeta42 is the critical component. In order
      to investigate this hypothesis, we have examined Abeta40/42-lipid interactions
      using in situ atomic force microscopy, electron microscopy and fluorescence
      anisotropy. While the association of Abeta42 with planar bilayers resulted in
      peptide aggregation but no fibre formation, this was not the case for Abeta40
      where we observed preferential fibre formation. Cholesterol, a key membrane
      component and modulating factor in AD, is inversely correlated with the extent of
      Abeta40/42-bilayer interaction. These results were confirmed using fluorescence
      anisotropy to evaluate the effect of Abeta on membrane fluidity and fluorimetry
      to confirm membrane integrity. Our results suggest that the enhanced
      amyloidogenic properties of Abeta42 are not correlated with fibril formation but
      aggregation on bilayer surfaces.

PMID- 14574628
TI  - Cholesterol modulates amyloid beta-peptide's membrane interactions.
AB  - The causal relationship between amyloid beta-peptide (Abeta) deposition and
      Alzheimer's disease (AD)-specific neuropathological lesions such as
      neurodegeneration and cortical atrophy is still not known. Mounting evidence
      points to alterations in cholesterol homeostasis occurring in AD brain that are
      probably linked to cerebral Abeta pathology. Interestingly, cholesterol not only
      modulates Abeta synthesis, but also controls interactions between Abeta and
      neuronal membranes that are regarded as decisive in the initiation of a
      neurotoxic cascade. This review focuses on the impact of cholesterol on membrane
      disordering effects of Abeta. Cholesterol is known to be an essential modulator
      of physicochemical state and functional activity in physiological membranes, and
      thus plays an essential role in the regulation of synaptic function and cell
      plasticity. In vitro and in vivo modulation of membrane cholesterol levels affect
      different cholesterol pools within the plasma membrane bilayer that are
      differentially sensitive to Abeta's disrupting effects. Membrane acyl-chains in
      the hydrocarbon core are most susceptible to Abeta. In this membrane region,
      cholesterol attenuates the membrane disordering effects of Abeta. This
      cholesterol pool is modulated by methyl-beta-cyclodextrin (MbetaCD) treatment in
      vitro. On the other hand, statin treatment in vivo depletes a cholesterol pool in
      a membrane area, which is much less susceptible to Abeta's membrane-disrupting
      effects. Our findings clearly implicate an involvement of cholesterol in brain
      membrane alterations occurring during AD. Disease-related changes in membrane
      cholesterol metabolism may be subtle and restricted to defined membrane pools
      since total membrane cholesterol levels are mainly unchanged in AD brain. Thus,
      elucidation of the structure and function of different cholesterol pools is
      necessary in understanding the coherence between cholesterol and AD.

PMID- 14574629
TI  - Cholesterol trafficking and amyloid beta peptides.
AB  - Currently, there is much interest in the association between cholesterol and
      Alzheimer's disease. An especially important aspect of this association is the
      relationship between amyloid beta-peptide (Abeta) and cholesterol that can be
      described as a reciprocal process. It would appear that cholesterol levels
      modulate Abeta levels and in turn Abeta acts on cholesterol homeostasis. Herein,
      we give a brief overview of amyloid beta peptide effects cellular cholesterol
      trafficking and potential mechanisms of those effects. Alterations of cholesterol
      homeostasis can have pronounced consequences on cell structure and function and
      may be both a cause and casualty of Alzheimer's disease.

PMID- 14574630
TI  - The ethnic nose. Preface.

PMID- 14574631
TI  - Considerations in ethnic rhinoplasty.
AB  - Although it is difficult to define specific ethnic groups as they are multiracial
      mixtures determined by historical, geographical, and cultural factors, we can
      define basically five non-Caucasian groups that commonly request rhinoplasty. The
      specific anatomy, surgical options, implant material, grafts, and possible
      complications are discussed. The importance of blending the "new" nose with the
      ethnic features to achieve harmony in the facial aesthetic components is
      emphasized.

PMID- 14574632
TI  - Non-Caucasian rhinoplasty.
AB  - Non-Caucasian patients seeking rhinoplasty often have similar goals as their
      Caucasian counterparts. However, surgeon sensitivity to ethnic variations and
      patient desires are crucial to a successful outcome. This article presents some
      of the commonly encountered issues seen in non-Caucasian rhinoplasty, including
      minimal modification, augmentation materials, and complications with infected and
      extruded implants.

PMID- 14574633
TI  - Mestizo rhinoplasty.
AB  - Cosmetic rhinoplasty is performed by specialists all over the world;
      increasingly, people of different ethnic groups want their noses reshaped in one
      way or another. The term mestizo is defined and its general nasal characteristics
      and anthropometric measurements are presented. Surgery is planned using the
      patient's specific facial characteristics, with the goal of achieving harmony and
      balance while preserving ethnical background and complying as much as possible
      with the patient's desires. All surgeries are performed using the open
      rhinoplasty approach. Mestizo patients usually want noses that look finer and
      thinner but not necessarily bigger. Different surgical options are presented and
      overall results evaluated, always trying to maintain ethnicity and harmony unless
      the patient desires otherwise.

PMID- 14574634
TI  - The ethnic nose.
AB  - There are distinctive anatomical differences between the non-Caucasian
      (platyrrhine, mesorrhine) nose and the Caucasian (leptorrhine) nose. In general,
      non-Caucasian patients requesting aesthetic rhinoplasty desire improvement and
      refinement of their noses with preservation of defining ethnic characteristics.
      Surgeons who perform rhinoplasty in this patient population must be familiar with
      the variations in nasal anatomy and implement augmentation rather than reduction
      techniques to achieve the desired aesthetic and functional outcomes. We provide a
      brief review of recent historical trends in ethnic rhinoplasty, highlight
      relevant anatomical differences, and describe our strategy for addressing the
      challenges of ethnic rhinoplasty.

PMID- 14574635
TI  - Rhinoplasty for the Mediterranean nose.
AB  - Homogenization of world culture through communications media, refinements in
      surgical techniques, and improved rhinoplasty results have resulted in a more
      extended dissemination of rhinoplasty among non-Caucasians. This request has led
      to increasingly anatomic, morphologic, and anthropometrical studies of the non
      Caucasian nose upon which surgical techniques have been proposed and addressed to
      create in these patients nasal features typical of a Caucasian-looking nose.
      There are few reports in medical literature concerning rhinoplasty that
      specifically address particular Caucasian ethnic groups (Anglo-Saxon, Germanic,
      Latin, and Slavic). Generally included within the Latin group are subjects
      presenting both paradigmatic nasal morphologies (typically, the classic "Greek,"
      "Roman," and "French" noses) and important cultural differences that greatly
      influence the subjective perception of the defect and, therefore, the type of
      change requested. These challenging conditions require a highly "customized"
      approach, both in the phase of the preoperative planning and in the choice of
      surgical options. The authors, by means of a photographic analysis systematically
      used with all their rhinoplasty patients, have identified some archetypes of
      nasal pyramid configurations that are typical of the reference population (44%
      Northern Italy, 15% Central Italy, 41% Southern Italy) and, on the basis of a
      medium/long-term evaluation of the relationship between adopted surgical
      techniques and results, propose some surgical options that are specific for every
      nasal archetype. This categorization helps the surgeon carry out a structured
      preoperative aesthetical analysis and provides him/her with both an anticipation
      of what findings to expect and the ability to deal with already diagnosed
      problems. Every archetype shows strong similarities in terms of preoperative
      analysis, surgical solutions, and subjective perception of the success of the
      surgery. The surgical options used proved to be apt to modify some paradigmatic
      defects in a satisfactorily predictable way. Combining the different tesserae of
      this puzzle to reach the goal of a satisfied patient (and not necessarily a
      beautiful nose) makes rhinoplasty a true challenge that requires a special talent
      from the surgeon: combining analysis capabilities, surgical logic, and manual
      skills with artistic sensitivity.

PMID- 14574637
TI  - [Referral by a general practitioner versus self-referral to a specialist
      practice. A comparison using chronic venous insufficiency as an example].
AB  - BACKGROUND AND OBJECTIVE: The gate-keeping role of general practitioners (GPs) is
      currently the topic of much debate in Germany. Currently it is possible for
      patients in Germany to see a specialist either through referral by their GP or
      directly through self-referral. To determine whether the gate-keeping role of GPs
      has a filtering effect, we compared patients referred by their GPs with self
      referred patients presenting with suspected chronic venous insufficiency (CVI) to
      a specialist practice. PATIENTS AND METHODS: From September to December 2001, we
      prospectively recruited 316 patients seen for suspected CVI in a specialist
      practice for vascular surgery and phlebology. Symptoms and clinical findings were
      recorded using a standardized form. RESULTS: 58.2 % of patients were referred by
      their GPs. These patients were on average 6 years older and presented at a more
      advanced stage of disease than self-referred patients. No difference was found
      between patients with and without referral with respect to the symptoms reported
      or the therapy recommended by the specialist. CVI was excluded in 7.1 % of
      patients with a referral and in 6.8 % of those without a referral. CONCLUSIONS:
      The majority of patients consulting a specialist were referred by their GP. The
      more advanced disease stage of these patients indicates that a filtering process
      occurs in referral by GPs. However, the share of patients without referrals in
      whom CVI could be excluded was low and not significantly different from that of
      patients with referrals. This indicates that misdiagnosis due to self-referral is
      relatively modest. A cost reduction effect in a gate-keeper system could
      therefore only be small.

PMID- 14574636
TI  - [Moderate alcohol consumption and plasma concentration of sensitive markers of
      inflammation. Comment on an atheroprotective relationship].
AB  - BACKGROUND AND OBJECTIVE: Changes in lipoproteins and hemostasis only
      incompletely explain the reduced cardiovascular mortality associated with light
      to moderate alcohol consumption. Since increasing evidence suggests that
      atherosclerosis can be considered to be a chronic inflammatory process, we sought
      to assess the association between daily alcohol consumption and levels of
      sensitive markers of inflammation. STUDY PARTICIPANTS AND METHODS: 478 voluntary
      blood donors (358 men, 120 women) aged 40 to 68 years were categorized into four
      groups according to their self-reported amount of daily alcohol consumption: 0
      g/day, >0 - 20 g/day, >20 - 40 g/day, and > 40 g/day. Means of various sensitive
      markers of inflammation (C-reactive protein (CRP), serum amyloid A (SAA),
      interleukin-6 (IL-6), intercellular adhesion molecule-1, plasma viscosity und
      albumin) were calculated and compared by bivariate and multivariate analyses.
      RESULTS: More than 80 % of the study participants reported to consume alcohol,
      mainly beer. We found statistically significantly decreased levels of SAA, CRP,
      and plasma viscosity in subjects with light-to-moderate alcohol intake (>0 - 20
      g/day and > 20 - 40 g/day, respectively), and a trend for increased levels of
      albumin in these subjects compared to non-drinkers. After multivariable
      adjustment for potential confounders (age, gender, body mass index, cigarette
      smoking, years of school education, and physical activity) a significant U-shaped
      association (p = 0.02) between levels of SAA and the amount of daily alcohol
      intake remained: there were 0.75 mg/l and 0.70 mg/l lower mean levels,
      respectively, of SAA in subjects with light-to-moderate alcohol intake compared
      to those of non-drinkers. Subjects with an alcohol intake of > 40 grams per day
      showed a statistically significant increase in levels of interleukin-6 (0.50
      pg/ml) compared to non-drinkers. CONCLUSION: Potential anti-inflammatory
      properties of moderate alcohol consumption might represent an additional
      mechanism to explain its atheroprotective effect.

PMID- 14574638
TI  - [Intrapericardial fibrinolysis as a therapeutic option in a case of purulent
      pericarditis].
AB  - HISTORY AND ADMISSION FINDINGS: A 23-year-old man known to have Hodgkin's disease
      in remission and C-protein deficiency presented with chest pain and symptoms of
      respiratory infection. INVESTIGATIONS: A purulent pericardial effusion was
      detected by echocardiography. The chest X-ray showed a left-sided pneumonia.
      TREATMENT AND CLINICAL COURSE: When pericardiocentesis failed to drain the
      purulent but pathogen-free effusion completely, streptokinase was several times
      instilled intrapericardially and achieved fibrinolysis without complication. The
      effusion did not recur. CONCLUSIONS: Intrapericardial application of fibrinolytic
      agents seems to be an effective treatment of a purulent pericarditis.

PMID- 14574639
TI  - [Citalopram].

PMID- 14574640
TI  - [Facultative paraneoplasia of the skin].

PMID- 14574641
TI  - [Polycystic ovary syndrome: significance of insulin resistance].

PMID- 14574642
TI  - [Cost-effectiveness of prophylaxis and treatment of influenza].

PMID- 14574643
TI  - Replication inhibitors modulate instability of an expanded trinucleotide repeat
      at the myotonic dystrophy type 1 disease locus in human cells.
AB  - Gene-specific CTG/CAG repeat expansion is associated with at least 14 human
      diseases, including myotonic dystrophy type 1 (DM1). Most of our understanding of
      trinucleotide instability is from nonhuman models, which have presented mixed
      results, supporting replication errors or processes independent of cell division
      as causes. Nevertheless, the mechanism occurring at the disease loci in patient
      cells is poorly understood. Using primary fibroblasts derived from a fetus with
      DM1, we have shown that spontaneous expansion of the diseased (CTG)(216) allele
      occurred in proliferating cells but not in quiescent cells. Expansions were
      "synchronous," with mutation frequencies approaching 100%. Furthermore, cells
      were treated with agents known to alter DNA synthesis but not to directly damage
      DNA. Inhibiting replication initiation with mimosine had no effect upon
      instability. Inhibiting both leading- and lagging-strand synthesis with
      aphidicolin or blocking only lagging strand synthesis with emetine significantly
      enhanced CTG expansions. It was striking that only the expanded DM1 allele was
      altered, leaving the normal allele, (CTG)(12), and other repeat loci unaffected.
      Standard and small-pool polymerase chain reaction revealed that inhibitors
      enhanced the magnitude of short expansions in most cells threefold, whereas 11%
      25% of cells experienced gains of 122-170 repeats, to sizes of (CTG)(338)
      (CTG)(386). Similar results were observed for an adult DM1 cell line. Our results
      support a role for the perturbation of replication fork dynamics in DM1 CTG
      expansions within patient fibroblasts. This is the first report that repeat
      length alterations specific to a disease allele can be modulated by exogenously
      added compounds.

PMID- 14574644
TI  - Mutations in a gene encoding a novel SH3/TPR domain protein cause autosomal
      recessive Charcot-Marie-Tooth type 4C neuropathy.
AB  - Charcot-Marie-Tooth disease type 4C (CMT4C) is a childhood-onset demyelinating
      form of hereditary motor and sensory neuropathy associated with an early-onset
      scoliosis and a distinct Schwann cell pathology. CMT4C is inherited as an
      autosomal recessive trait and has been mapped to a 13-cM linkage interval on
      chromosome 5q23-q33. By homozygosity mapping and allele-sharing analysis, we
      refined the CMT4C locus to a suggestive critical region of 1.7 Mb. We
      subsequently identified mutations in an uncharacterized transcript, KIAA1985, in
      12 families with autosomal recessive neuropathy. We observed eight distinct
      protein-truncating mutations and three nonconservative missense mutations
      affecting amino acids conserved through evolution. In all families, we identified
      a mutation on each disease allele, either in the homozygous or in the compound
      heterozygous state. The CMT4C gene is strongly expressed in neural tissues,
      including peripheral nerve tissue. The translated protein defines a new protein
      family of unknown function with putative orthologues in vertebrates. Comparative
      sequence alignments indicate that members of this protein family contain multiple
      SH3 and TPR domains that are likely involved in the formation of protein
      complexes.

PMID- 14574645
TI  - A comparison of bayesian methods for haplotype reconstruction from population
      genotype data.
AB  - In this report, we compare and contrast three previously published Bayesian
      methods for inferring haplotypes from genotype data in a population sample. We
      review the methods, emphasizing the differences between them in terms of both the
      models ("priors") they use and the computational strategies they employ. We
      introduce a new algorithm that combines the modeling strategy of one method with
      the computational strategies of another. In comparisons using real and simulated
      data, this new algorithm outperforms all three existing methods. The new
      algorithm is included in the software package PHASE, version 2.0, available
      online (http://www.stat.washington.edu/stephens/software.html).

PMID- 14574646
TI  - Protein-truncating mutations in ASPM cause variable reduction in brain size.
AB  - Mutations in the ASPM gene at the MCPH5 locus are expected to be the most common
      cause of human autosomal recessive primary microcephaly (MCPH), a condition in
      which there is a failure of normal fetal brain development, resulting in
      congenital microcephaly and mental retardation. We have performed the first
      comprehensive mutation screen of the 10.4-kb ASPM gene, identifying all 19
      mutations in a cohort of 23 consanguineous families. Mutations occurred
      throughout the ASPM gene and were all predicted to be protein truncating.
      Phenotypic variation in the 51 affected individuals occurred in the degree of
      microcephaly (5-11 SDs below normal) and of mental retardation (mild to severe)
      but appeared independent of mutation position.

PMID- 14574648
TI  - Meta-analysis and a large association study confirm a role for calpain-10
      variation in type 2 diabetes susceptibility.

PMID- 14574647
TI  - Origin and diffusion of mtDNA haplogroup X.
AB  - A maximum parsimony tree of 21 complete mitochondrial DNA (mtDNA) sequences
      belonging to haplogroup X and the survey of the haplogroup-associated
      polymorphisms in 13,589 mtDNAs from Eurasia and Africa revealed that haplogroup X
      is subdivided into two major branches, here defined as "X1" and "X2." The first
      is restricted to the populations of North and East Africa and the Near East,
      whereas X2 encompasses all X mtDNAs from Europe, western and Central Asia,
      Siberia, and the great majority of the Near East, as well as some North African
      samples. Subhaplogroup X1 diversity indicates an early coalescence time, whereas
      X2 has apparently undergone a more recent population expansion in Eurasia, most
      likely around or after the last glacial maximum. It is notable that X2 includes
      the two complete Native American X sequences that constitute the distinctive X2a
      clade, a clade that lacks close relatives in the entire Old World, including
      Siberia. The position of X2a in the phylogenetic tree suggests an early split
      from the other X2 clades, likely at the very beginning of their expansion and
      spread from the Near East.

PMID- 14574649
TI  - Guidelines reduce x-ray and blood gas utilization in acute asthma.
AB  - Using a retrospective chart review, we compared the use of chest radiography
      (CXR) and arterial blood gas testing (ABG) before (pre-P) and after (post-P)
      initiation of specific ordering guidelines for the use of these studies for
      patients presenting to the ED with acute asthma exacerbation. We noted the number
      of tests performed, the indication for the test, and the results when performed.
      There was a 55% reduction in the number of chest radiographs (85 of 213 patients
      pre-P had CXR as compared with 40 of 222 patients post-P, P <.001). Of the
      patients who did not have a chest x-ray in the ED, none had an abnormal chest x
      ray obtained after admission or if they returned to the ED within 72 hours. There
      was a 57% reduction in the number of arterial blood gases post-P (9 of 222
      patients) as compared with pre-P (20 of 213 patients, P <.001). Although patients
      with abnormal ABGs had a discernible indication for testing, all of the ABGs for
      which no indication could be found were normal. A protocol containing criteria
      for obtaining chest x-rays and arterial blood gas testing can reduce the use of
      diagnostic testing, thereby improving ED efficiency without adversely impacting
      patient care.

PMID- 14574650
TI  - Violence prevention in the ED: linkage of the ED to a social service agency.
AB  - Interpersonal violence continues to be a problem in the United States, most
      prominent in the inner-city minority young persons population. The medical
      approach of "treat 'em and street 'em" philosophy has led to foregoing the
      psychosocial needs of injured young persons. This study describes a program to
      link young persons who are victims of interpersonal violence to a healthcare
      system and a social service agency in an effort to meet their psychosocial needs.
      An unvalidated screening tool was developed by a team consisting of an EP, social
      worker, and public health scientist to determine the young victims' psychosocial
      needs. Patients aged 10 to 24 years who were victims of interpersonal violence
      (excluding child abuse, sexual assault, and domestic violence) were randomly
      assigned in the study. The control group was given a list of services and the
      treatment group received an assessment, case management, and referral to
      appropriate resources. The study site was a community, teaching level 1 trauma
      center. The study was approved by the institutional review board. Numbers of
      referrals in both groups were counted and compared using SPSS (version 10,
      Chicago, IL). One hundred eighty-eight victims of interpersonal violence were
      enrolled. A total of 82.5% were male, 65.4% were African American and 31.4% were
      Hispanic. At the end of 6 months, 78 of the 96 young persons (81.3%) in the
      treatment group made one or more contacts with their case manager and made use of
      social service, healthcare, and other referrals. Education (21.6%), job readiness
      (19.1%), and mental health (11.9%) were the most frequently used services. Nine
      of the 92 (9.8%) in the control group used services; most of these referrals were
      for social services (7 of 9 respondents) and the others were healthcare-related.
      The difference in utilization of services between the treatment and the control
      groups were found to be significant different (95% confidence interval, 1.41
      1.55, significance =.00), and there was a strong positive correlation of using
      services and case management (Pearson coefficient = 0.728, significance =.00).
      The referral of young victims of violence from the ED to psychosocial services
      could be successful using a case management model and an alliance between a
      healthcare system and a social service agency.

PMID- 14574651
TI  - Increased blood lead levels in severe smoke inhalation.
AB  - Lead-containing paint is common in structures built before 1977. Heated lead in
      burning paint can be aerosolized and absorbed directly into the bloodstream
      through the lungs. Acute lead intoxication has been reported in this setting. The
      objective of this study was to determine if victims of severe smoke inhalation
      secondary to closed-space fires have clinically important elevated blood lead
      levels. A case-control study, with a 2:1 ratio of cases to controls, was matched
      for age and sex. Cases were drawn from a prospective convenience sample of
      intubated victims of closed-space fires presenting to the ED of an urban tertiary
      burn center. Cases had blood lead levels obtained 24 hours postexposure. Matched
      control subjects had blood lead levels obtained during ED evaluation for a
      complaint unrelated to smoke inhalation. The difference between mean lead levels
      for cases and control subjects was expressed with a 95% confidence interval (CI).
      Among 22 cases, the mean lead level was 6.64 mug/dL (standard deviation [SD],
      4.14 mug/dL). Among the 44 matched control subjects, mean lead level was 2.89
      mug/dL (SD, 1.65 mug/dL). The mean difference between cases and control subjects
      was 3.75 mug/dL (95% confidence interval, 1.86-5.64). Although severe smoke
      inhalation is associated with a more than 2-fold statistically significant
      increase in blood lead levels, there is no evidence to suggest that these
      elevations are clinically important.

PMID- 14574652
TI  - Epidemiology of adverse effects of prehospital sedation analgesia.
AB  - The aim of this study was to introduce a continuous monitoring of side effects
      related to sedation-analgesia in the field. A document was completed by
      physicians on board the ambulances for all prehospital interventions and checked
      daily by the medical staff. A total of 3605 interventions were evaluated over a
      12-month period. Six hundred four patients undertook analgesia and/or sedation:
      group 1 (spontaneously breathing patients) n = 289 and group 2 (intubated
      ventilated patients) n = 315. Sixty-four percent of patients received intravenous
      opioids in group 1. The anesthetic technique used for intubation was the rapid
      sequence induction in 70% of patients. Side effects were observed in 5.5% in
      group 1 (nausea: 2%, hypotension: 1%, hypoxemia: 1%) and 22% of patients in group
      2 (hypotension-arrhythmia: 12%, cardiac arrest: 2%, difficult intubation: 5%,
      hypoxemia: 1%, pulmonary aspiration: 1%, laryngospasm/bronchospasm: 2%). No death
      was related to these medications. A close monitoring of side effects related to
      sedation-analgesia must be included in a quality program to improve patient
      safety in the field.

PMID- 14574653
TI  - Blunt pediatric head trauma requiring neurosurgical intervention: how subtle can
      it be?
AB  - Recent literature on pediatric head injuries has suggested that important
      intracranial injuries might present to the ED without typical signs or symptoms.
      The objective of our study was to review our institutional experience with head
      injured infants and young children to assess the subtlety of the ED presentation.
      We performed a retrospective medical record review of head-injured children </=10
      years of age who underwent neurosurgical procedures from January 1, 1985, through
      November 28, 2001. We identified 110 children who met our inclusion criteria. All
      of the children had at least 2 signs or symptoms indicative of head injury. No
      single sign or symptom was present in all cases. Altered mental status was
      identified 85% of the time and was the most common sign or symptom. Eighteen
      children presented with a Glasgow Coma Scale score of 15 or the absence of
      abnormal mental status documented, but all of these children had other
      indications for head computed tomographic scanning. Emergency physicians should
      feel confident that standard history and physical examination skills are adequate
      to identify head-injured children who require neurosurgical procedures.

PMID- 14574655
TI  - Sensitivity in detecting free intraperitoneal fluid with the pelvic views of the
      FAST exam.
AB  - The multiple-view focused assessment with sonography for trauma (FAST) exam is an
      integral tool in the assessment of blunt abdominal trauma. A prospective
      observational study was performed to compute the average minimum volume of
      detectable intraperitoneal fluid with the pelvic views of the FAST exam. All
      adult patients from October 1999 to May 2001, who presented to the ED with blunt
      abdominal trauma and underwent a clinically indicated diagnostic peritoneal
      lavage (DPL), were candidates for admission to the pelvic ultrasound study. In
      the supine position, patients were administered lavage fluid in 100 cc increments
      until the examiner detected the fluid on ultrasound. An independent reviewer also
      examined the hard-copy ultrasound images for fluid detection. Patients were
      excluded if they had (1) a positive DPL for hemoperitoneum (defined as 10 cc of
      gross blood or >100,000 red blood cells/mL), (2) a positive initial ultrasound
      for free fluid, or (3) lacked sufficient hard-copy ultrasound images. The mean
      minimal volume of fluid needed for pelvic ultrasound detection by the examiner
      and reviewer was 157 and 129 cc (n = 7), respectively. The median quantity of
      fluid for ultrasound detection by both the examiner and reviewer was 100 cc. The
      pelvic views of the FAST exam identified a significantly smaller quantity of
      intraperitoneal fluid than previous studies of the right upper quadrant single
      view exam.

PMID- 14574654
TI  - Severe manifestations of coricidin intoxication.
AB  - CoricidinHBP (Schering-Plough Health Care Products, Inc, Memphis, TN) is a
      popular over-the-counter product abused by teenagers for its potent euphoric
      properties. Clinically significant signs and symptoms after ingestion are usually
      short-lived and commonly include tachycardia, hypertension, somnolence, and
      agitation. We report 2 cases of severe toxicity from CoricidinHBP in adolescents
      that required prolonged hospitalization. The first case demonstrates prolonged
      anticholinergic complications from a suicidal attempt with CoricidinHBP. The
      second case demonstrates significant acetaminophen-induced hepatotoxicty from
      recreational use of CoricidinHBP Maximum Strength Flu. Adolescent abuse of these
      products is encouraged because of the easily accessible medium of the Internet.
      The significant morbidity seen in our cases clearly demonstrates the need for
      vigilance by health care professionals regarding the abuse of over-the-counter
      products.

PMID- 14574656
TI  - Cardiac troponin I as a predictor of respiratory failure in children hospitalized
      with respiratory syncytial virus (RSV) infections: a pilot study.
AB  - This pilot study was performed to assess the use of cardiac troponin I to predict
      respiratory failure in children admitted to the hospital with respiratory
      syncytial virus (RSV) infections. We enrolled a prospective convenience sample of
      children under 5 years of age who were admitted to our university-based, tertiary
      care children's hospital from December 1, 2000, to February 1, 2002, with RSV
      infections. A cardiac troponin I was drawn at admission. We assessed the test
      characteristics for positive cardiac troponin I (defined as >0.3 ng/mL, the
      manufacturer's upper limit of normal) in correctly identifying children who had
      respiratory failure as evidenced by the need for endotracheal intubation. Twenty
      five children from 9 days to 38 months of age were included. Ten children had a
      positive cardiac troponin I and 3 of these children had respiratory failure. A
      positive cardiac troponin I demonstrated a sensitivity of 100%, specificity 68%,
      positive predictive value of 30%, negative predictive value of 100%, and accuracy
      of 72%. The area under the receiver operating characteristic curve was 0.939 (95%
      confidence interval, 0.820-1.0), suggesting a high degree of discriminatory power
      in selecting children with respiratory failure. A sample size calculation
      revealed that a follow-up study of 359 patients is needed before the clinical use
      of cardiac troponin I for this purpose.

PMID- 14574657
TI  - ED leadership competency matrix: an administrative management tool.
AB  - A successful ED relies on its leaders to master and demonstrate core competencies
      to be effective in the many arenas in which they interact and are responsible. A
      unique matrix model for the assessment of an ED leadership's key administrative
      skill sets is presented. The model incorporates capabilities related to the
      individual's cognitive aptitude, experience, acquired technical skills,
      behavioral characteristics, as well as the ability to manage relationships
      effectively. Based on the personnel inventory using the matrix, focused
      evaluation, development, and recruitment of ED key leaders occurs. This dynamic
      tool has provided a unique perspective for the evaluation and enhancement of
      overall ED leadership performance. It is hoped that incorporation of such a model
      will similarly improve the accomplishments of EDs at other institutions.

PMID- 14574659
TI  - Hematuria as an indicator for the presence or absence of urinary calculi.
AB  - The purpose of this study was to determine whether the presence of hematuria or
      its absence can predict the presence or absence of urinary calculi as determined
      by computed tomography (CT) scan in patients presenting to the ED with acute
      abdominal colic. We reviewed the urine analysis and CT scans of all patients
      presenting to the ED over a 12-month period with acute colic and a clinical
      suspicion of urinary calculi. Urine samples were drawn on arrival in the ED
      before CT scanning. Two hundred seventy-seven patients were included in the
      study. The prevalence of urinary stones as detected by CT was 57.4%. The positive
      predictive value, negative predictive value, and accuracy for hematuria as a
      marker for stone disease was 60.9%, 72.4%, and 62.1%, respectively. A total of
      3.24% of patients had some degree of obstruction, all of whom had hematuria. The
      absence of hematuria is not a reliable exclusion criterion for urinary calculi.
      The detection of urinary stones without hematuria does not imply obstruction.

PMID- 14574658
TI  - A simple and rapid approach to hypokalemic paralysis.
AB  - Hypokalemia with paralysis (HP) is a potentially reversible medical emergency. It
      is primarily the result of either hypokalemic periodic paralysis (HPP) caused by
      an enhanced shift of potassium (K(+)) into cells or non-HPP resulting from
      excessive K(+) loss. Failure to make a distinction between HPP and non-HPP could
      lead to improper management. The use of spot urine for K(+) excretion rate and
      evaluation of blood acid-base status could be clinically beneficial in the
      diagnosis and management. A very low rate of K(+) excretion coupled with the
      absence of a metabolic acid-base disorder suggests HPP, whereas a high rate of
      K(+) excretion accompanied by either metabolic alkalosis or metabolic acidosis
      favors non-HPP. The therapy of HPP requires only small doses of potassium
      chloride (KCl) to avoid rebound hyperkalemia. In contrast, higher doses of KCl
      should be administered to replete the large K(+) deficiency in non-HPP.

PMID- 14574660
TI  - Screening with blood urea nitrogen before intravenous contrast.
AB  - In some settings, blood urea nitrogen (BUN) values are available well in advance
      of creatinine values. We wanted to determine whether BUN values can be used to
      screen for renal insufficiency for the purpose of intravenous contrast
      administration. From laboratory records, we derived and validated cutpoints for
      BUN values to detect creatinine values >/=2.0 mg/dL. "Sensitive" and "high-yield"
      cutpoints were derived using records from 5000 consecutive patients and validated
      using a random set of 2000 patients. BUN >/=15 mg/dL, the "sensitive" cutpoint,
      had sensitivity of 0.997 (95% confidence interval [CI], 0.987-1.0) and
      specificity of 0.56 (95% CI, 0.54-0.59). BUN >/=20 mg/dL, the "high-yield
      cutpoint," had sensitivity of 0.98 (95% CI, 0.95-0.99) and specificity of 0.71
      (95% CI, 0.69-0.73). Negative likelihood ratios for these cutpoints were 0.005
      and 0.03, respectively. BUN values <15-20 mg/dL provide strong evidence against
      renal insufficiency.

PMID- 14574661
TI  - Magnetic resonance imaging as a diagnostic adjunct to Wernicke encephalopathy in
      the ED.
AB  - This report describes usefulness of magnetic resonance imaging (MRI) for the
      evaluation of the patient suspected of Wernicke encephalopathy (WE). Magnetic
      resonance imaging shows characteristic findings of symmetric hyperintense lesions
      predominantly located in the bilateral medial thalami, the periaqueductal
      regions, and the mamillary bodies. The diagnosis of Wernicke encephalopathy has
      been based generally on history and clinical symptoms. We now believe that MRI
      could be used as a diagnostic adjunct in the patient suspected of WE.

PMID- 14574662
TI  - Cases in electrocardiography.

PMID- 14574663
TI  - Gestational transient thyrotoxicosis.

PMID- 14574664
TI  - Percutaneous transtracheal ventilation without a jet ventilator.

PMID- 14574665
TI  - Screening for anticholinergic abuse in patients with chronic mental illness.

PMID- 14574666
TI  - Functional decline in nonagenarians after a visit to an ED.

PMID- 14574667
TI  - Delayed massive hemoptysis complicated with aspiration of organophosphorus
      compound.

PMID- 14574668
TI  - Ruptured interstitial pregnancy presenting with negative beta-hCG and hypovolemic
      shock.

PMID- 14574669
TI  - Use of pharmaceutical promotility agents in the treatment of body packers.

PMID- 14574670
TI  - Pericardial hemorrhage secondary during computed tomography scanning for aortic
      dissecting aneurysm.

PMID- 14574671
TI  - Management of blunt trauma victims with significant hemoperitoneum with normal
      examination.

PMID- 14574675
TI  - Transient expression of doublecortin during adult neurogenesis.
AB  - During development of the central nervous system, expression of the microtubule
      binding protein doublecortin (DCX) is associated with migration of neuroblasts.
      In addition to this developmental role, expression of DCX remains high within
      certain areas of the adult mammalian brain. These areas, mainly the dentate gyrus
      and the lateral ventricle wall in conjunction with the rostral migratory stream
      and olfactory bulb, retain the capacity to generate new neurons into adulthood.
      Adult neurogenesis is typically detected by incorporation of bromodeoxyuridine
      (BrdU) into dividing cells and colabeling of BrdU-positive cells with markers for
      mature neurons. To elucidate whether DCX could act as an alternative indicator
      for adult neurogenesis, we investigated the temporal expression pattern of DCX in
      neurogenic regions of the adult brain. Analysis of newly generated cells showed
      that DCX is transiently expressed in proliferating progenitor cells and newly
      generated neuroblasts. As the newly generated cells began expressing mature
      neuronal markers, DCX immunoreactivity decreased sharply below the level of
      detection and remained undetectable thereafter. The transient expression pattern
      of DCX in neuronal committed progenitor cells/neuroblasts indicates that DCX
      could be developed into a suitable marker for adult neurogenesis and may provide
      an alternative to BrdU labeling. This assumption is further supported by our
      observation that the number of DCX-expressing cells in the dentate gyrus was
      decreased with age according to the reduction of neurogenesis in the aging
      dentate gyrus previously reported.

PMID- 14574676
TI  - Spatial representation of odorant structure in the moth antennal lobe: a study of
      structure-response relationships at low doses.
AB  - How odorant structure and concentration are spatially represented within the
      primary olfactory integration center, the antennal lobe (AL) or olfactory bulb
      (OB) in invertebrates and vertebrates, respectively, is currently a topic of high
      interest. Here, we show the spatial representation of odorant structure in the
      antennal lobe of the moth Spodoptera littoralis by imaging calcium activity
      evoked by straight chain aliphatic alcohols and aldehydes at low doses. Activity
      patterns of a given odor were most similar to compounds with the same functional
      group, differing in chain length by only one carbon atom. A chain length
      dependency was present as the most activated glomerulus in the lobe shifted from
      a medial to a lateral position with increasing chain length of the molecule.
      Statistical analysis revealed that in both classes of chemicals the chain length
      of the molecule was represented in a similar way. No topographically fixed
      domains were observed for any of the classes. However, activity patterns evoked
      by lower chain length molecules were spatially more distinct than patterns evoked
      by higher chain length molecules. The number of activated glomeruli for both
      classes of chemicals increased with increasing chain length to reach a maximum at
      eight or nine C atoms followed by a decrease as the chain length further
      increased.

PMID- 14574677
TI  - Cell surface carbohydrates and glomerular targeting of olfactory sensory neuron
      axons in the mouse.
AB  - Cell surface carbohydrates have been implicated in axon guidance and targeting
      throughout the nervous system. We have begun to test the hypothesis that, in the
      olfactory system, a differential distribution of cell surface carbohydrates may
      influence olfactory sensory neuron (OSN) axon targeting. Specifically, we have
      examined the spatial distribution of two different plant lectins, Ulex europaeus
      agglutinin (UEA) and Dolichos biflorus agglutinin (DBA), to determine whether
      they exhibit differential and reproducible projections onto the main olfactory
      bulb. Each lectin exhibited a unique spatial domain of glomerular labeling that
      was consistent across animals. UEA labeling was strongest in the ventral aspect
      of the olfactory bulb; DBA labeling was strongest in the dorsal aspect of the
      olfactory bulb. Some evidence for colocalization was present where these two
      borders intersected. Large areas of the glomerular layer were not labeled by
      either lectin. To determine whether patterns of lectin labeling were reproducible
      at the level of individual glomeruli, UEA labeling was assessed relative to M72
      IRES-taulacZ- and P2-IRES-taulacZ-labeled axons. Although glomeruli neighboring
      these two identified glomeruli were consistently labeled with UEA, none of the
      lacZ positive axons was lectin labeled. Labeling of vomeronasal sensory neuron
      axons in the accessory olfactory bulb was more uniform for the two lectins. These
      data are the first to show a differential distribution of UEA vs. DBA labeling in
      the main olfactory bulb and are consistent with the hypothesis that a
      differential distribution of cell surface carbohydrates, a glycocode, may
      contribute to the targeting of OSN axons.

PMID- 14574678
TI  - Synapse replacement in the striatum of the adult rat following unilateral cortex
      ablation.
AB  - Defining the selective pattern of synapse replacement that occurs in different
      areas of the damaged brain is essential for predicting the limits of functional
      compensation that can be achieved after various types of brain injury. Here we
      describe the time course of dendritic reorganization, spine loss and recovery,
      and synapse replacement in the striatum following a unilateral cortex ablation.
      We found that the time course for the transient loss and recovery of dendritic
      spines on medium spiny I (MSI) neurons, the primary postsynaptic target for
      corticostriatal axons, paralleled the time course for the removal of degenerating
      axon terminals from the neuropil and the formation of new synapses on MSI
      neurons. Reinnervation of the deafferented striatum occurred chiefly by axon
      terminals that formed asymmetric synapses with dendritic spines of MSI neurons,
      and the mean density of asymmetric synapses recovered to 86% of the sham-operated
      rat value by 30 days postlesion. In addition, the synaptic circuitry of the
      reconstructed striatum was characterized by an increase in the number of multiple
      synaptic boutons (MSBs), i.e., presynaptic axon terminals that make contact with
      more than one dendritic spine. Whether the postsynaptic contacts of MSBs are
      formed with the dendritic spines of the same or a different parent dendrite in
      the striatum is unknown. Nevertheless, these data suggest that the formation of
      MSBs is an essential part of the compensatory response to the loss of input from
      the ipsilateral cortex following the aspiration lesion and may serve to modulate
      activity-dependent adaptive changes in the reconstructed striatum that can lead
      to functional recovery.

PMID- 14574679
TI  - Nicotinic acetylcholine receptor distribution in relation to spinal
      neurotransmission pathways.
AB  - Neuronal nicotinic receptors (nAChR) are pentameric assemblies of subunits of a
      gene family where specified combinations of alpha and beta subunits form
      functional receptors. To extend our understanding of the role of spinal nAChR in
      the processing of sensory stimuli and regulation of autonomic and motor
      responses, we initiated investigations to localize nAChR subunit expression
      within discrete spinal regions and cell types. High-affinity epibatidine binding
      was present in the superficial dorsal and ventral horns, the mediolateral and
      central canal regions. RT-PCR identified transcripts for alpha3, alpha4, alpha5,
      beta2, and beta4 in both spinal cord parenchyma and dorsal root ganglia (DRG).
      Our affinity-purified antibodies against alpha3, alpha4, alpha5, beta2, and beta4
      subunits identified specific protein bands of appropriate molecular mass
      (preadsorbed with the respective antigens) in specific tissues and cells that
      express nicotinic receptors, including the spinal cord and DRG neurons. Having
      established the absence of crossreactivity with related subunits, specific
      fluorescence labeling of nerve terminals and cell bodies was achieved and
      correlated with the distribution of defined marker proteins and nicotinic
      receptor binding sites determined autoradiographically. Our findings indicate
      that alpha3, alpha4, alpha5, beta2, and beta4 subunits are all expressed on
      primary afferents (IB4-positive terminals) in the spinal cord. The predominant
      presynaptic (synaptophysin colocalization) labeling is in the superficial layer
      of the dorsal horn. These receptor subunits, except for beta4, are also present
      in postsynaptic autonomic (anti-bNOS-positive) and somatic motor neurons (anti
      VAChT-positive). The alpha3, alpha5, and beta2 subunits showed additional
      staining in glial (anti-GFAP-positive) cells. These studies reveal a dense and
      distinguishable distribution of nAChR subunits in the spinal cord and point
      toward future therapeutic targeting for specific spinal actions.

PMID- 14574680
TI  - Green fluorescent protein expression and colocalization with calretinin,
      parvalbumin, and somatostatin in the GAD67-GFP knock-in mouse.
AB  - Gamma-aminobutyric acid (GABA)ergic neurons in the central nervous system
      regulate the activity of other neurons and play a crucial role in information
      processing. To assist an advance in the research of GABAergic neurons, here we
      produced two lines of glutamic acid decarboxylase-green fluorescence protein
      (GAD67-GFP) knock-in mouse. The distribution pattern of GFP-positive somata was
      the same as that of the GAD67 in situ hybridization signal in the central nervous
      system. We encountered neither any apparent ectopic GFP expression in GAD67
      negative cells nor any apparent lack of GFP expression in GAD67-positive neurons
      in the two GAD67-GFP knock-in mouse lines. The timing of GFP expression also
      paralleled that of GAD67 expression. Hence, we constructed a map of GFP
      distribution in the knock-in mouse brain. Moreover, we used the knock-in mice to
      investigate the colocalization of GFP with NeuN, calretinin (CR), parvalbumin
      (PV), and somatostatin (SS) in the frontal motor cortex. The proportion of GFP
      positive cells among NeuN-positive cells (neocortical neurons) was approximately
      19.5%. All the CR-, PV-, and SS-positive cells appeared positive for GFP. The CR
      , PV, and SS-positive cells emitted GFP fluorescence at various intensities
      characteristics to them. The proportions of CR-, PV-, and SS-positive cells among
      GFP-positive cells were 13.9%, 40.1%, and 23.4%, respectively. Thus, the three
      subtypes of GABAergic neurons accounted for 77.4% of the GFP-positive cells. They
      accounted for 6.5% in layer I. In accord with unidentified GFP-positive cells,
      many medium-sized spherical somata emitting intense GFP fluorescence were
      observed in layer I.

PMID- 14574681
TI  - Development of a sexually dimorphic neuromuscular system in male rats after
      spinal transection: morphologic changes and implications for estrogen sites of
      action.
AB  - The lumbar spinal cord of rats contains the sexually dimorphic, steroid-sensitive
      spinal nucleus of the bulbocavernosus (SNB). In male rats, SNB motoneurons
      exhibit a biphasic pattern of dendritic growth, having an initial period of
      exuberant growth followed by a period of retraction to mature lengths by 7 weeks
      of age. This growth is steroid dependent: dendrites fail to grow after
      castration, but growth is supported in castrates treated with estradiol. In this
      experiment, we examined whether supraspinal afferent input by means of descending
      spinal tracts to the SNB was involved in the normal postnatal development of SNB
      motoneurons, and whether the effect of estradiol on SNB dendritic growth could be
      explained by an indirect action of estradiol on supraspinal afferents. Motoneuron
      morphology was assessed in normal males, early- or late-postnatally transected
      males, castrated males left untreated or treated with estradiol, and transected
      castrates treated with estradiol. SNB motoneurons were retrogradely labeled with
      cholera toxin-horseradish peroxidase during both the growth and retraction phases
      of dendritic development and reconstructed in three dimensions. The removal of
      supraspinal afferents resulted in extremely local effects within the developing
      SNB arbor, as well as transient alterations in somal growth. Furthermore, spinal
      transection did not block the trophic effect of estradiol on supporting SNB
      dendritic growth, indicating that estrogens do not act by means of supraspinal
      input to support SNB motoneuron development.

PMID- 14574682
TI  - Brain-derived neurotrophic factor regulates expression of vasoactive intestinal
      polypeptide in retinal amacrine cells.
AB  - Brain-derived neurotrophic-factor (BDNF) is expressed in the retina and controls
      the development of subtypes of amacrine cells. In the present study we
      investigated the effects of BDNF on amacrine cells expressing vasoactive
      intestinal polypeptide (VIP). Rats received three intraocular injections of BDNF
      on postnatal days (P) 16, 18, and 20. The animals were sacrificed on P22, P40,
      P60, P80, and P120, and VIP expression in their retinas was detected by
      immunohistochemistry (P22, P40) and by radioimmunoassay (RIA; P22, P40, P60, P80,
      P120) to assess the time course of BDNF effects on VIP. A significant increase in
      the density of VIP-positive amacrine cells was detected in BDNF-treated retinas,
      and VIP concentration was up-regulated by 150% both at P22 and at P40 with
      respect to untreated controls. VIP concentration then slowly declined in the
      treated retinas over a period of 3 months; however, a statistically significant
      increase of 50% was still detectable on P120. The impact of endogenous BDNF on
      the regulation of VIP expression in the retina was analyzed in mice homozygous
      for a targeted deletion of the BDNF gene locus (bdnf-/-). VIP
      immunohistochemistry revealed a marked reduction of VIP-positive amacrine cells
      and of VIP-immunopositive processes in the inner plexiform layer of the BDNF
      knockout mice. Mice lacking BDNF expressed only 5% of the VIP protein in their
      retinas compared with the retinas of wild-type mice as measured by RIA. Our data
      show that BDNF is a major regulator of VIP expression in retinal amacrine cells
      and exerts long-lasting effects on VIP content.

PMID- 14574683
TI  - Organization of somatosensory cortex in the laboratory rat (Rattus norvegicus):
      Evidence for two lateral areas joined at the representation of the teeth.
AB  - Lateral somatosensory areas have not been explored in detail in rats, and
      theories on the organization of this region are based largely on anatomical
      tracing experiments. We investigated the topography of this region by using
      microelectrode recordings, which were related to flattened cortical sections
      processed for cytochrome oxidase (CO). Two lateral somatosensory areas were
      identified, each containing a complete representation of the body. A larger, more
      medial representation formed a mirror image of S1 along the rostrocaudal axis of
      the head region corresponding to the previously identified secondary
      somatosensory area (S2). A smaller, more lateral representation formed a mirror
      image of S2 along the rostrocaudal axis of the forelimb and hindlimb regions and
      likely corresponds to the parietal ventral area (PV) identified in other mammals.
      We also investigated the representation of the dentition and identified regions
      of cortex responsive to tooth stimulation. The lower incisor representation was
      rostral to the lower lip region of S1, and the upper incisor representation was
      lateral to the buccal pad region of S1. The upper and lower incisors flanked the
      tongue representation. An additional large region of far lateral cortex responded
      to both incisors. Finally, five CO-dense modules were consistently identified
      rostral and lateral to the S1 face representation, which we refer to as OM1, OM2,
      OM3, FM, and HM. These modules closely correspond to the physiologically
      identified areas representing the lower incisor (OM1) and tongue (OM2) regions of
      S1 and the mixed tooth (OM3), forelimb (FM1), and hindlimb (HM) representations
      of S2 and PV.

PMID- 14574684
TI  - Expression of constitutively active p21H-rasval12 in postmitotic pyramidal
      neurons results in increased dendritic size and complexity.
AB  - The small G protein p21Ras is a critical molecular switch for relaying
      neurotrophic actions and is essential for normal functioning and plasticity of
      the nervous system. In this study, the morphogenetic effects of p21Ras were
      investigated on neurons in vivo. Morphological changes of layers II/III and Vb
      commissural pyramidal neurons of the primary somatosensory cortex were analyzed
      in transgenic mice expressing permanently active p21H-RasVal12 in postmitotic
      neurons. Pyramidal cells were retrogradely labelled with biotinylated dextran
      amine and subsequently traced using Neurolucida. Compared with wild-type mice,
      transgenic animals showed a significant increase in the surface area and volume
      of basal dendrites on the proximal and intermediate segments in layers II/III and
      on further distal segments in layer V. In addition, the surface area and volume
      of the trunk and of the proximal segments of oblique branches of apical dendrites
      were enlarged in both layers. Sholl analyses of basal and apical dendrites showed
      a significant increase in dendritic complexity of layer V neurons. A positive
      correlation was observed between the size of the basal dendrite and the neuronal
      soma size in the transgenic population, indicating that growth-promoting effects
      of p21H-RasVal12 affect both cellular compartments in parallel. However, the
      dendritic surface correlated with the number of tips and dendritic stem diameter
      in both wild-type and transgenic populations, demonstrating that these relations
      represent rather conservative design principles in dendritic morphology. The data
      presented here suggest an important role of p21Ras-dependent signaling in the
      final differentiation and maintenance of dendritic morphology.

PMID- 14574685
TI  - Supplementation-dependent differences in the rates of embryonic stem cell self
      renewal, differentiation, and apoptosis.
AB  - Although it is known that leukemia inhibitory factor (LIF) supports the
      derivation and expansion of murine embryonic stem (ES) cells, it is unclear
      whether this is due to inhibitory effects of LIF on ES cell differentiation or
      stimulatory effects on ES cell survival and proliferation. Using an ES cell line
      transgenic for green fluorescent protein (GFP) expression under control of the
      Oct4 promoter, we were able to simultaneously track the responses of live Oct4
      GFP-positive (ES) and -negative (differentiated) fractions to LIF, serum, and
      other growth factors. Our findings show that, in addition to inhibiting
      differentiation of undifferentiated cells, the administration of LIF resulted in
      a distinct dose-dependent survival and proliferation advantage, thus enabling the
      long-term propagation of undifferentiated cells. Competitive responses from the
      differentiated cell fraction could only be elicited upon addition of serum,
      fibroblast growth factor-4 (FGF-4), or insulin-like growth factor-1 (IGF-1). The
      growth factors did not induce additional differentiation of ES cells, but rather
      they significantly improved the proliferation of already differentiated cells.
      Our analyses show that, by adjusting culture conditions, including the type and
      amount of growth factors or cytokines present, the frequency of media exchange,
      and the presence or absence of serum, we could selectively and specifically alter
      the survival, proliferation, and differentiation dynamics of the two
      subpopulations, and thus effectively control population outputs. Our findings
      therefore have important applications in engineering stem cell culture systems to
      predictably generate desired stem cells or their derivatives for various
      regenerative therapies.

PMID- 14574686
TI  - Organic tissues in rotating bioreactors: fluid-mechanical aspects, dynamic growth
      models, and morphological evolution.
AB  - This analysis deals with advances in tissue-engineering models and computational
      methods as well as with novel results on the relative importance of "controlling
      forces" in the growth of organic constructs. Specifically, attention is focused
      on the rotary culture system, because this technique has proven to be the most
      practical solution for providing a suitable culture environment supporting three
      dimensional tissue assemblies. From a numerical point of view, the growing
      biological specimen gives rise to a moving boundary problem. A "volume-of
      fraction" method is specifically and carefully developed according to the complex
      properties and mechanisms of organic tissue growth and, in particular, taking
      into account the sensitivity of the construct/liquid interface to the effect of
      the fluid-dynamic shear stress (it induces changes in tissue metabolism and
      function that elicit a physiological response from the biological cells). The
      present study uses available data to introduce a set of growth models. The
      surface conditions are coupled to the transfer of mass and momentum at the
      specimen/culture-medium interface and lead to the introduction of a group of
      differential equations for the nutrient concentration around the sample and for
      the evolution of tissue mass displacement. The models are then used to show how
      the proposed surface kinetic laws can predict (through sophisticated numerical
      simulations) many of the known characteristics of biological tissues grown using
      rotating-wall perfused vessel bioreactors. This procedure provides a validation
      of the models and associated numerical method and also gives insight into the
      mechanisms of the phenomena. The interplay between the increasing size of the
      tissue and the structure of the convective field is investigated. It is shown
      that this interaction is essential in determining the time evolution of the
      tissue shape. The size of the growing specimen plays a critical role with regard
      to the intensity of convection and the related shear stresses. Convective
      effects, in turn, are found to impact growth rates, tissue size, and morphology,
      as well as the mechanisms driving growth. The method exhibits novel capabilities
      to predict and elucidate experimental observations and to identify cause-and
      effect relationships.

PMID- 14574687
TI  - Minimization of carbon losses in pilot-scale outdoor photobioreactors by model
      based predictive control.
AB  - The optimization of carbon use in pilot-scale outdoor tubular photobioreactors is
      investigated in this study. The behavior of a 0.20-m(3) tubular photobioreactor
      was studied, with and without algae, by steady-state and pulse dynamic-response
      analysis experiments. A model of the system was obtained and implemented in a
      programmable control unit and was used to control the reactor under normal
      production conditions. Results showed that, using and on-off control, the mean
      daily CO(2) flow in the reactor was 0.86 g min(-1), 19.7% of this being lost. By
      using a predictive control algorithm the mean daily CO(2) flow was reduced to
      0.74 g min(-1), with losses being reduced to 15.6%. In this case, pH tracking was
      not adequate, especially at the beginning and end of the daylight period, because
      the variation in solar irradiance was not considered. Taking solar irradiance
      into account resulted in better performance, with mean daily CO(2) flow reduced
      to 0.70 g min(-1), and carbon losses reduced to 5.5%. pH tracking was improved
      and valve actuation was reduced. Improvement of pH control reduced pH gradients
      in the culture, which increased the photosynthesis rate and biomass productivity
      of the system. Biomass productivity increased from 1.28 to 1.48 g L(-1) day-(1)
      when on-off control was replaced by model-based predictive control plus solar
      irradiance effect mode. Implementation of this methodology in outdoor
      photobioreactors can increase productivity by 15% and reduce the cost of
      producing biomass by >6%. Clearly, application of effective control techniques,
      such as model-based predictive control (MPC), must be considered when developing
      these processes.

PMID- 14574688
TI  - Swirling flow implementation in a photobioreactor for batch and continuous
      cultures of Porphyridium cruentum.
AB  - Light is the main limiting factor in photoautotrophic-intensive production of
      microorganisms, and improvement of its use is an important concern for
      photobioreactor design and operation. Swirling flows, which are known to improve
      mass and photon transfers, were applied to annular light chambers of a
      photobioreactor and studied by simulation and microalgal culture. Two
      hydrodynamic conditions were compared: axial flow generating poor radial mixing,
      and tangential flow generating three-dimensional swirling motion. Batch and
      continuous cultures of the Rhodophyte Porphyridium cruentum were performed in a
      100-L, 1.5-m(2), fully controlled photobioreactor with eight light chambers. The
      inlet design of these chambers was modified to create the hydrodynamic conditions
      for comparison. Various intensities of swirling motion were used, characterized
      by the velocity factor (VF), defined as the ratio between annular chamber flow
      and inlet aperture sections. Experiments were performed within the range of
      photon flux densities (PFD) optimizing the yield of light energy transformation
      into living substance for the species and the temperature used. Culture kinetics
      with swirling flows generated by apertures of VF = 2, 4, and 9 were compared with
      pseudoaxial VF = 2 chosen as reference. Batch cultures with VF = 4 swirling flow
      showed no significant difference, whereas continuous cultures proved more
      discriminating. Although no significant difference was obtained for VF = 2, a 7%
      increase of steady-state productivity and a 26% decrease in time required to
      reach this steady state were obtained with VF = 4 swirling flow. This beneficial
      effect of swirling flow could have accounted for increased mixing. Conversely, VF
      = 9 swirling flow resulted in a 9% decrease of steady-state productivity and a 9%
      increase in the time required to reach this steady state, a negative effect that
      could have accounted for increased shear stress. CO(2) bioconversion yield at
      steady state showed a 34% increase for VF = 4. These results suggest that
      swirling motion makes microalgal cultures more efficient, provided that the
      resulting adverse effects remain acceptable. Experimental investigation was
      completed by a theoretical approach in which simulation of continuous cultures of
      P. cruentum was based on the hydrodynamic conditions achieved in the
      photobioreactor. Although the results obtained with pseudoaxial flow were
      correctly predicted, simulations with swirling flow showed a marked enhancement
      of productivity not observed experimentally. The influence of side effects
      induced by increased mixing (particularly hydrodynamic shear stress) was
      considered with respect to modeling assumptions. Comparison of experimental
      results with theoretical simulation provided a better understanding of the mixing
      effect, a key factor in improving the efficiency of such bioprocesses.

PMID- 14574689
TI  - Bioscrubbing of waste gas-substrate absorber to avoid instability induced by
      inhibition kinetics.
AB  - The stability of a continuous stirred tank bioreactor treating a gas stream
      containing monochlorobenzene (MCB) was studied theoretically and experimentally.
      A bioreactor inoculated with Pseudomonas sp. strain JS150 was submitted to
      successive step disturbances in the MCB load, inducing washout and system
      instability. With time, and subject to high MCB concentrations in the biomedium,
      the microorganisms appeared to adapt to high MCB load, and needed increasingly
      severe shocks to induce washout. To improve the bioreactor stability, the
      influence of an MCB-absorber prior to the bioreactor was investigated, using
      silicone oil as the absorbent for MCB. A parallel was established with the first
      set of experiments (no absorber). Phase plane plots showed how the presence of
      the absorber changed the system trajectories from washout into stable pseudo
      steady states. Experimental results confirmed the benefits of the absorber in
      avoiding washout under high MCB loads. At periods of low loading, MCB was
      desorbed from the absorber. For the same loading conditions, removal efficiencies
      were much higher than when no absorber was present. Elimination capacities
      observed in the bioreactor were much higher than those previously reported for
      biotrickling filters treating MCB containing gas streams: 300 to 450 g m(-3) h(
      1). Gas inlet concentrations were in the range 12 to 65 g m(-3), well above the 5
      g m(-3) upper limit usually suggested for biological treatment of waste gases,
      showing that highly concentrated gas streams may be biologically treated so long
      as inhibitory concentrations are not reached in the bioreactor.

PMID- 14574690
TI  - Dynamic behavior of adsorber membranes for protein recovery.
AB  - In recent years there has been a considerable interest in developing membrane
      chromatography systems that function as a short, wide chromatographic column in
      which the adsorptive packing consists of one or more microporous membranes. This
      study reports the use of new adsorber membranes prepared by the incorporation of
      various types of ion exchange resins into an EVAL porous membrane for protein
      recovery. The obtained heterogeneous matrixes composed of solid particles
      surrounded by the polymeric film possess a good accessibility for the protein to
      the adsorptive sites. Furthermore, small particles can be embedded into porous
      polymeric structures without the disadvantages of classical chromatographic
      columns (high pressure drop, fouling and plugging sensitivity, low flow rate),
      but with the advantages of membrane technology (easy scale-up, low-pressure drop,
      high flow rate). The adsorptive membranes feature high static as well as dynamic
      protein adsorption capacities for operating flow rates ranging from 200 to 400 L
      h bar per m(2) and ionic strength of 20-200 mM. In a sequential desorption step
      by changing the pH and/or the ionic strength of the eluent, up to 90% protein
      recovery was obtained. Next to the separation, the mixed matrix adsorber membrane
      functions as a concentration medium since the protein can be concentrated up to
      20-fold in the eluent. The adsorber membranes can be reused in multiple
      adsorption/desorption cycles with good adsorption performances.

PMID- 14574691
TI  - Efficient anaerobic whole cell stereoselective bioreduction with recombinant
      Saccharomyces cerevisiae.
AB  - In this study we investigate the NADPH-dependent stereoselective reduction of the
      bicyclic diketone bicyclo[2.2.2]octane-2,6-dione (BCO2,6D) to the chiral
      ketoalcohol (1R,4S,6S)-6-hydroxybicyclo[2.2.2]octane-2-one (BCO2one6ol). Our aim
      was to develop a whole cell batch process for reduction of carbonyl substrates
      with (i) a high cosubstrate yield (formed product/consumed cosubstrate) and (ii)
      a high conversion rate under anaerobic conditions with Saccharomyces cerevisiae
      as biocatalyst and glucose as cosubstrate. Five open reading frames (ORFs),
      YMR226c, YDR368w, YOR120w, YGL157w, and YGL039w, encoding reductases involved in
      the conversion of BCO2,6D were identified using cell-free extract from strains
      belonging to the ExClone collection (yeast ORF expression clones; ResGen,
      Invitrogen Corp., UK). We report the one-step purification and characterization
      of three major BCO2,6D reductases, YMR226cp, YDR368wp (YPR1p), and YOR120wp
      (GCY1p). The reductases were overexpressed under a strong constitutive promoter
      and the impact on cosubstrate yield, conversion time, glucose consumption rate,
      and reduction rate was investigated when reductases were overexpressed either
      alone or in combination with low phosphoglucose isomerase activity (encoded by
      YBR196c). Combining overexpression of BCO2,6D reductase with reduced glycolytic
      rate (low phosphoglucose isomerase activity) offers a fast whole cell
      stereoselective bioreduction system useful for facilitated anaerobic batch
      conversions.

PMID- 14574692
TI  - Primmorphs from archaeocytes-dominant cell population of the sponge hymeniacidon
      perleve: improved cell proliferation and spiculogenesis.
AB  - Marine sponges (Porifera) possess an extraordinary diversity of bioactive
      metabolites for new drug discovery and development. In vitro cultivation of
      sponge cells in a bioreactor system is very attractive for the sustainable
      production of sponge-derived bioactive metabolites; however, it is still a
      challenging task. The recent establishment of sponge primmorphs, multicellular
      aggregates from dissociated mixed-cell population (MCP), has been widely
      acknowledged to hold great promise for cultivation in vitro. Here we present a
      new method to establish an in vitro sponge primmorph culture from archaeocyte
      dominant cell population (ADCP) enriched by a Ficoll gradient, rather than a
      mixed-cell population (MCP). Our rationale is based upon the totipotency (the
      ability of a cell to differentiate into other cell types) of archaeocyte cells
      and the different biological functions of various sponge cell types. A sponge,
      Hymeniacidon perleve collected from the China Yellow Sea was used as a model
      system for this investigation. Distinct dynamics of primmorph formation were
      observed while significant increases in DNA synthesis, cell proliferation (up to
      threefold), and cell growth (up to fourfold) were achieved. Furthermore, a time
      dependent spiculogenesis was clearly demonstrated in our longterm culture,
      indicating high metabolic activity of primmorphs from the ADCP. This new method
      represents an important step forward to advance sponge cell culture in vitro that
      may lead to commercial exploitation of sponge-derived drugs.

PMID- 14574693
TI  - Effect of mixing rate on beta-carotene production and extraction by dunaliella
      salina in two-phase bioreactors.
AB  - beta-Carotene has many applications in the food, cosmetic, and pharmaceutical
      industries; Dunaliella salina is currently the main source for natural beta
      carotene. We have investigated the effect of mixing rate and whether it leads to
      the facilitated release of beta-carotene from the cells of Dunaliella salina in
      two-phase bioreactors. Three pairs of bioreactors were inoculated at the same
      time, operated at 100, 150, and 170 rounds per minute, respectively, and
      illuminated with a light intensity of 700 micromol m(-2) s(-1). Each pair
      consisted of one bioreactor containing only aqueous phase for the blank and one
      containing the water phase together with dodecane, which is biocompatible with
      the cells. Comparison of the viability and growth of the cells grown under
      different agitation rates shows that 170 rpm and 150 rpm are just as good as 100
      rpm. The presence and absence of the organic phase also has no influence on the
      viability and growth of the cells. In contrast to the growth rate, the extraction
      rate of beta-carotene is influenced by the stirrer speed. The extraction rate
      increases at a higher stirring rate. The effectiveness of extraction with respect
      to power input is comparable for all the applied mixing rates, even though it is
      slightly lower for 100 rpm than the others. The chlorophyll concentration in the
      organic phase remained very low during the experiment, although at higher mixing
      rates, chlorophyll impurity increased up to 3% (w/w) of the total extracted
      pigments. At 170 rpm carotenoid and chlorophyll undergo the highest extraction
      rate for both pigments-0.5% of the chlorophyll and 6% of the carotenoid is
      extracted.

PMID- 14574694
TI  - On-line biomass monitoring of CHO perfusion culture with scanning dielectric
      spectroscopy.
AB  - In this work, dielectric spectroscopy was used to monitor two CHO perfusion
      culture experiments (B14 and B16). The capacitance of the cell suspension was
      recorded every 20 minutes over an excitation frequency range of 0.2 MHz to 10.0
      MHz. A phase plot of the capacitance at a low excitation frequency vs. the value
      at a higher frequency proved to be an accurate indicator of the major transition
      points of the culture, i.e., maximum cell viability, end of lactate consumption,
      point of zero viability. For both experiments, the capacitance signal correlated
      very well (R(2) >0.98) with viable cell number up to concentrations of 1 x 10(7)
      cells/mL. Visual observation of the capacitance spectra indicated that changes in
      the capacitance relative to frequency were related to the cellular morphology. A
      multivariate model was developed using off-line data that could predict the
      median cell diameter within a single experiment (B14) with an error of 0.34
      microm (2%). Upon extension to a subsequent experiment (B16), the predicted error
      was 1.18 microm (9%).

PMID- 14574695
TI  - The influence of molecular variation on protein interactions.
AB  - We investigated the influence of solvation forces on protein-protein interactions
      for two forms of lysozyme: hen egg white (HEWL) and turkey egg white (TEWL).
      Turkey egg white has more surface exposed hydrophobic residues than HEWL and the
      protein-protein interactions of TEWL are shown to be more attractive than those
      of HEWL, for the conditions studied. The importance of including a solvation term
      in the potential of mean force model, to account for molecular variation in
      protein surface characteristics, is highlighted. We also show that the magnitude
      of this solvation term can be estimated using readily available data.

PMID- 14574696
TI  - Degradation of xenobiotics in a partitioning bioreactor in which the partitioning
      phase is a polymer.
AB  - Two-phase partitioning bioreactors (TPPBs) are characterized by a cell-containing
      aqueous phase and a second immiscible phase that contains toxic and/or
      hydrophobic substrates that partition to the cells at subinhibitory levels in
      response to the metabolic demand of the organisms. To date, the delivery phase in
      TPPBs has been a hydrophobic solvent that traditionally needed to possess a
      variety of important properties including biocompatibility, nonbioavailability,
      low volatility, and low cost, among others. In the present work we have shown
      that the organic solvent phase can be replaced by inexpensive polymer beads that
      function in a similar fashion as organic solvents, delivering a toxic substrate
      to cells based on equilibrium considerations. Specifically, 3.4 mm diameter beads
      of poly(ethylene-co-vinyl acetate) (EVA) were used to reduce the aqueous
      concentration of phenol in a bioreactor from toxic levels ( approximately 2,000
      mg/L) to subinhibitory levels ( approximately 750 mg/L), after which Pseudomonas
      putida ATCC 11172 was added to the system and allowed to consume the total phenol
      loading. Thus, the beads absorbed the toxic substrate and released it to the
      cells on demand. The EVA beads, which could be reused, were able to absorb 14 mg
      phenol/g EVA. This work has opened the possibility of using widely mixed cultures
      in TPPB systems without concern for degradation of the delivery material and
      without concern of contamination.

PMID- 14574697
TI  - Catalytic behaviors of enzymes attached to nanoparticles: the effect of particle
      mobility.
AB  - Nanoparticles provide an ideal remedy to the usually contradictory issues
      encountered in the optimization of immobilized enzymes: minimum diffusional
      limitation, maximum surface area per unit mass, and high effective enzyme
      loading. In addition to the promising performance features, the unique solution
      behaviors of the nanoparticles also point to a transitional region between the
      heterogeneous (with immobilized enzymes) and homogeneous (with soluble free
      enzymes) catalysis. The particle mobility, which is related to particle size and
      solution viscosity through Stokes-Einstein equation, may impact the reaction
      kinetics according to the collision theory. The mobility-activity relationship
      was examined through experimental studies and theoretical modeling in the present
      work. Polystyrene particles with diameters ranging from 110-1000 nm were
      prepared. A model enzyme, alpha-chymotrypsin, was covalently attached to the
      nanoparticles up to 6.6 wt%. The collision theory model was found feasible in
      correlating the catalytic activities of particles to particle size and solution
      viscosity. Changes in the size of particles and the viscosity of reaction media,
      which all affect the mobility of the enzyme catalyst, evidently altered the
      intrinsic activity of the particle-attached enzyme. Compared to K(M), k(cat)
      appeared to be less sensitive to particle size and viscosity.

PMID- 14574699
TI  - Measuring local flow velocities and biofilm structure in biofilm systems with
      magnetic resonance imaging (MRI).
AB  - The characterization of substrate transport in the bulk phase and in the biofilm
      matrix is one of the problems which has to be solved for the verification of
      biofilm models. Additionally, the surface structure of biofilms has to be
      described with appropriate parameters. Magnetic resonance imaging (MRI) is one of
      the promising methods for the investigation of transport phenomena and structure
      in biofilm systems. The MRI technique allows the noninvasive determination of
      flow velocities and biofilm structures with a high resolution on the sub
      millimeter scale. The presented investigations were carried out for defined
      heterotrophic biofilms which were cultivated in a tube reactor at a Reynolds
      number of 2000 and 8000 and a substrate load of 6 and 4 g/m2d glucose. Magnetic
      resonance imaging provides both structure data of the biofilm surface and flow
      velocities in the bulk phase and at the bulk/biofilm interface. It is shown that
      the surface roughness of the biofilms can be determined in one experiment for the
      complete cross section of the test tubes both under flow and stagnant conditions.
      Furthermore, the local shear stress was calculated from the measured velocity
      profiles. In the investigated biofilm systems the local shear stress at the
      biofilm surface was up to 3 times higher compared to the mean wall shear stress
      calculated on the base of the mean flow velocity.

PMID- 14574698
TI  - Enzymatic activity and stability of D-fructose dehydrogenase and sarcosine
      dehydrogenase immobilized onto giant vesicles.
AB  - Stable vesicles with diameters between about 1 and 10 mum were prepared by a
      particular emulsification technology that involved the use of the surfactants
      Span 80 and Tween 80 and the phospholipid lecithin (phosphatidylcholine from
      soybeans). Two membrane enzymes, d-fructose dehydrogenase from Gluconobacter sp.
      (FDH) and sarcosine dehydrogenase from Pseudomonas putida (SDH), were for the
      first time immobilized onto the bilayer membranes of these type of vesicles; and
      the catalytic activity and enzymatic stability were measured and compared with
      the enzymes in a vesicle-free solution. The enzyme activity as well as stability
      considerably increased upon immobilization. In particular, immobilized FDH at 25
      degrees C was stable for at least 20 days, while the activity of the free enzyme
      dropped to about 20% of its initial value during the same period of time. In
      contrast to FDH and SDH, immobilization of sorbitol dehydrogenase from
      Gluconobacter suboxydans (SODH) was not successful, as no improved activity or
      stability could be obtained.

PMID- 14574700
TI  - Higher expression of Fab antibody fragments in a CHO cell line at reduced
      temperature.
AB  - A chimeric Fab was expressed in Chinese hamster ovary cells under the control of
      the CMV promoter in a two-stage production process. Cells were first grown to 90%
      confluence at 37 degrees C in a proliferation phase, followed by a production
      phase at either 37 degrees C or 28 degrees C. Medium supplemented with serum and
      medium free from serum was tested in the production phase at both temperatures.
      Comparison of Fab expression revealed that reducing the temperature to 28 degrees
      C resulted in a 14-fold increase in product yield when cells were cultivated in
      serum-containing medium, and in a 38-fold increase in product yield when serum
      free medium was applied.

PMID- 14574701
TI  - High-level expression of full-length antibodies using trans-complementing
      expression vectors.
AB  - Recombinant antibodies are increasingly used as therapeutics for a wide variety
      of diseases. Generation of cell lines expressing high levels of recombinant
      antibody typically requires labor-intensive cloning and screening steps. We
      describe a mammalian expression system for the high-level production of full
      length antibody molecules. It has been shown that the dihydrofolate reductase
      (DHFR) selectable marker can be divided into two fragments that, with the aid of
      a leucine zipper, can re-associate to form an active molecule. Using bicistronic
      vectors, we linked the expression of each antibody chain to the expression of a
      DHFR fragment. Survival in selective media requires expression of both DHFR
      fragments that, by virtue of these vectors, also selects for the expression of
      both antibody chains. Initial pools produced 5 microg of Ab/10(6) cells/d (qP =
      microg/10(6) cells/d). Expression of each antibody chain in conjunction with a
      portion of DHFR also leads to concurrent amplification of both antibody chains in
      the presence of methotrexate, a DHFR inhibitor, and results in a two- to fivefold
      increase in antibody production with basal qPs ranging from 10-25 ug/10(6)
      cells/d. Shake-flask cultures of amplified pools produced up to 600 mg/L of
      antibody in 7 days. This system allows for rapid generation of antibodies without
      cloning and greatly simplifies selection of cell lines for the production of
      potential antibody therapeutics.

PMID- 14574702
TI  - Optical processing of bacterial libraries for directed evolution.
AB  - Selection of phenotypically distinct bacterial colonies on a Petri dish is
      typically performed by one of two methods: chemical or mechanical. Chemical
      methods (e.g., antibiotic selection) rely on inherent growth advantages of the
      unique phenotypes desired and thus have limited applicability. Mechanical methods
      are generally slow and require relatively large colonies (typically hundreds of
      colonies per plate). Here the use of imaged light to select bacterial colonies is
      explored, employing either photodynamic therapy agents or a ferrochelatase
      mutation in combination with porphyrin precursors to sensitize the bacteria to
      light and a computer-controlled light projection system to illuminate some
      bacterial colonies while leaving others in the dark. A CCD camera was used to
      distinguish between bacteria expressing green fluorescent protein (GFP) from
      nonfluorescent colonies. The fluorescence image from the camera was then used to
      create a virtual masking image for photoselection. Using a simple commercial
      projector it was possible to confer a 56-fold selective advantage to colonies
      expressing GFP. This represents a potentially powerful tool in directed evolution
      experiments using large libraries.

PMID- 14574703
TI  - One-pot enzymatic production of dTDP-4-keto-6-deoxy-D-glucose from dTMP and
      glucose-1-phosphate.
AB  - An enzymatic production method for dTDP-4-keto-6-deoxy-D-glucose, a key
      intermediate of various deoxysugars in antibiotics, was developed starting from
      dTMP, acetyl phosphate, and glucose-1-phosphate. Four enzymes, i.e., TMP kinase,
      acetate kinase, dTDP-glucose synthase, and dTDP-D-glucose 4,6-dehydratase' were
      overexpressed using T7 promoter system in the E. coli BL21 strain, and the dTDP-4
      keto-6-deoxy-D-glucose was synthesized by using the enzyme extracts in one-pot
      batch system. When 20 mM dTMP of initial concentration was used, Mg2+ ion, acetyl
      phosphate, and glucose-1-phosphate concentrations were optimized. About 95%
      conversion yield of dTDP-4-keto-6-deoxy-D-glucose was obtained based on initial
      dTMP concentration at 20 mM dTMP, 1 mM ATP, 60 mM acetyl phosphate, 80 mM glucose
      1-phosphate, and 20 mM MgCl(2). The rate-limiting step in this multiple enzyme
      reaction system was the dTDP-glucose synthase reaction. Using the reaction
      scheme, about 1 gram of purified dTDP-4-keto-6-deoxy-D-glucose was obtained in an
      overall yield of 81% after two-step purification, i.e., anion exchange
      chromatography and gel filtration.

PMID- 14574704
TI  - Development of a fed-batch fermentation process to overproduce
      phosphoenolpyruvate carboxykinase using an expression vector with promoter and
      plasmid copy number controllable by heat.
AB  - To effectively achieve tight regulation and high-level expression of cloned
      genes, a novel expression plasmid has been developed to contain the promoter and
      allow the plasmid copy number to be controlled by heat. The feasibility of the
      plasmid was tested by overproducing the pck gene product (Pck), a protein
      responsible for cell growth on gluconeogenic carbons and with potential toxicity.
      By fusing the pck gene with the promoter on the plasmid, the Escherichia coli
      strain harboring the composite vector was shown to produce various amounts of Pck
      in response to different degrees of heat shock. With the use of a 30 degrees -
      >41 degrees C stepwise upshift, the shake-flask culture of recombinant cells
      enabled production of maximal Pck in soluble form accounting for 20% of total
      cell protein. In sharp contrast, Pck production was undetectable in the uninduced
      cell, and this was further confirmed by the failed growth of strain JCL1305,
      defective in the essential genes for gluconeogenesis, carrying the composite
      vector on succinate at 30 degrees C. By exploiting the fed-batch fermentation
      approach, the recombinant cell batch initially kept at 30 degrees C in a lab
      scale fermentor was exposed to 41 degrees C for 2 h at the batch fermentation
      stage, followed by a reduction in temperature to 37 degrees C throughout the
      remainder of the culturing process. Consequently, this resulted in Pck production
      equivalent to 15% of total cell protein. The total Pck yield thus calculated was
      amplified 1880-fold over that obtained at the shake-flask scale. Overall, there
      is great promise for this expression system due to its tight control, high
      production, simple thermomodulation, and feasible scale-up of recombinant
      proteins.

PMID- 14574705
TI  - Baculoviral polyhedrin as a novel fusion partner for formation of inclusion body
      in Escherichia coli.
AB  - Baculoviral polyhedrin, which originated from Autographa californica nuclear
      polyhedrosis virus (AcNPV), was employed for the first time as a novel fusion
      partner for expression of foreign proteins in an Escherichia coli system. We
      characterized the expression of recombinant polyhedrin protein fused to green
      fluorescent protein (GFP). The polyhedrin fusion protein ( approximately 58 kDa)
      was successfully expressed as an insoluble inclusion body comprising
      approximately 30% of the total cellular protein. The E. coli expressing
      polyhedrin-GFP fusion protein showed higher cell growth ( approximately 1.8-fold)
      and higher GFP yield ( approximately 3.5-fold) than the strain expressing soluble
      single GFP. Interestingly, the polyhedrin fusion portion showed almost the same
      characteristics as the native baculoviral polyhedrin; it was rapidly solubilized
      under alkaline conditions, similar to the conditions found in the insect midgut.
      In addition, the polyhedrin fusion portion was rapidly digested by alkaline
      proteases in insect Plutella xylostella midgut as well as by alpha-chymotrypsin,
      a protease that has similar properties to insect midgut polyhedra-associated
      alkaline proteases. These unique properties suggest that baculoviral polyhedrin
      might be an advantageous fusion partner for production of foreign proteins,
      especially harmful proteins, in E. coli expression systems.

PMID- 14574706
TI  - Further studies related to the scale-up of high cell density Escherichia coli fed
      batch fermentations: the additional effect of a changing microenvironment when
      using aqueous ammonia to control pH.
AB  - In this work, we report on the further development of the scale-down, two
      compartment (STR + PFR) experimental simulation model. For the first time, the
      effect on high cell density Escherichia coli fed-batch fermentations of a
      changing microenvironment with respect to all three of the major spatial
      heterogeneities that may be associated with large-scale processing (pH, glucose,
      and dissolved oxygen concentration) were studied simultaneously. To achieve this,
      we used traditional microbiological analyses as well as multiparameter flow
      cytometry to monitor cell physiological response at the individual cell level. It
      was demonstrated that for E. coli W3110 under such conditions in a 20 m(3)
      industrial fed-batch fermentation, the biomass yield is lower and final cell
      viability is higher than those found in the equivalent well-mixed, 5L laboratory
      scale case. However, by using a combination of the well-mixed 5L stirred tank
      reactor (STR) with a suitable plug flow reactor (PFR) to mimic the changing
      microenvironment at the large scale, very similar results to those in the 20 m(3)
      reactor may be obtained. The similarity is greatest when the PFR is operated with
      a mean residence time of 50 sec with a low level of dO(2) and a high glucose
      concentration with either a pH of 7 throughout the two reactors or with pH
      controlled at 7 in the STR by addition into the PFR where the pH is > 7.

PMID- 14574707
TI  - Catalytic features of monoclonal antibody i41SL1-2 subunits.
AB  - A monoclonal antibody (mAb), i41SL1-2, was obtained by immunizing the peptide of
      complementarity-determining region-1 (CDRL-1: RSSKSLLYSNGNTYLY) of a super
      catalytic antibody light chain, 41S-2-L, capable of enzymatically destroying the
      gp41 molecule of the HIV-1 envelope. From the DNA and the deduced amino acid
      sequences of the light and heavy chain of i41SL1-2 mAb, molecular modeling was
      conducted that suggested that both subunits of i41SL1-2 mAb possess catalytic
      triads in their structures. Especially the light chain of i41SL1-2 mAb possesses
      a characteristic catalytic triad composed of Asp(1), Ser(27A), and His(93), whose
      positions are identical to the catalytic antibody light chain, VIPase, of S. Paul
      and colleagues (see text). The antibody gene of i41SL1-2 light chain and VIPase
      belong to the same germline, bd2, suggesting that the discrete germline
      inherently possesses catalytic activity. Both light and heavy chains of i41SL1-2
      mAb degraded the antigenic peptide CDRL-1 within 47 and 57 h, respectively. The
      catalytic reaction constant (kcat) of the light and heavy chain was 6.1 x 10(-1)
      and 6.2 x 10(-1) min(-1), respectively. These are high values for the natural
      catalytic antibodies reported so far. The catalytic efficiency (kcat/Km) of the
      light and heavy chain was 3.1 x 10(5) and 4.9 x 10(4) M(-1) min(-1),
      respectively. The first cleaved bond of the antigenic peptide by subunits of
      i41SL1-2 mAb was between Arg(1) and Ser(2) in the sequence of CDRL-1, suggesting
      a serine protease character.

PMID- 14574708
TI  - Purification of histidine-tagged single-chain Fv-antibody fragments by metal
      chelate affinity precipitation using thermoresponsive copolymers.
AB  - Metal chelate affinity precipitation (MCAP) has been successfully developed as a
      simple purification process for proteins that have affinity for metal ions. The
      present lack of widespread applications for this technique as compared to
      immobilized metal affinity chromatography (IMAC) may be related to the scarcity
      of well-characterized metal affinity macroligands (AML) and their applications to
      the number of different purification systems. In the present work we describe a
      detailed study of a new purification system using metal-loaded thermoresponsive
      copolymers as AML. The copolymers of vinylimidazole (VI) with N
      isopropylacrylamide (NIPAM) were synthesized by radical polymerization with
      imidazole contents of 15 and 24 mol%. When loaded with Cu(II) and Ni(II) ions the
      copolymers selectively precipitated extracellularly expressed histidine-tagged
      single-chain Fv-antibody fragments (His(6)-scFv fragments) from the fermentation
      broth free from E. coli cells. Precipitation was induced by salt at mild
      temperatures and the bound antibody fragments were recovered by dissolving the
      protein-polymer complex in EDTA buffer and subsequent reprecipitation of the
      polymer. His(6)-scFv fragments were purified with yields of 91 and 80% and
      purification folds of 16 and 21 when Cu(II) and Ni(II) copolymers were used,
      respectively. The protein precipitation capacity of the Ni(II) copolymer showed a
      dependence on the VI concentration in the copolymer. The SDS-PAGE pattern showed
      significant purification of the antibody fragments.

PMID- 14574709
TI  - [Surgical treatment for benign diseases of the esophagus].

PMID- 14574710
TI  - [Surgical treatment for reflux esophagitis].
AB  - Recently, proton pump inhibitors and the laparoscopic Nissen operation were
      introduced clinically for the treatment of reflux esophagitis. Although the
      laparoscopic Nissen operation is becoming increasingly common world wide, medical
      therapy is still considered the treatment of choice for reflux esophagitis. The
      indications for surgical treatment of reflux esophagitis are: 1) patients
      resistant to medical therapy, especially younger patients; 2) free reflux
      patients; 3) patients with shortened esophagus or stenosis; and 4) patients with
      respiratory complications. The selection of surgical method is as follows: 1) the
      fundamentally laparoscopic Nissen procedure should be selected for relatively
      younger patients with good peristalsis in the esophageal body; 2) the
      laparoscopic Toupet method or the Dor method should be selected for patients with
      poor esophageal peristalsis; 3) the Tokai University method is suitable for
      patients with any condition; 4) the Collis-Nissen method, modified Deitel method,
      or Deitel-Nissen method is suitable for patients with acquired short esophagus;
      5) resection and jejunal interposition or double tract reconstruction should be
      performed in patients with severe stenosis. Numerous problems remain in the
      surgical treatment of reflux esophagitis.

PMID- 14574711
TI  - [Laparoscopic repair of esophageal hiatal hernia].
AB  - Hiatal hernias are usually classified into three distinct types: type I, sliding
      hernia; type II, paraesophageal hernia; and type III, a combination of type I and
      II hernias. Presentation of type I hernia is so-called reflux symptoms, in
      contrast with the symptoms associated with mechanical obstruction of the
      herniated stomach in type II and III hernias. Surgical indications for type I
      hernia depend upon the severity of esophagitis. In type II and III hernias,
      severe symptoms and complications represent the chief indications for repair.
      Totally intrathoracic stomach hernias generally present such a risk of volvulus,
      strangulation, and perforation that surgery is indicated even in asymptomatic and
      uncomplicated cases. Although the pathophysiology is different, the Nissen
      procedure is the surgical procedure of choice for both types of hiatal hernia.
      Since the first report in 1993, the laparoscopic Nissen procedure has gained wide
      acceptance. We have so far experienced 26 cases of hiatal hernia, 18 of type I
      and 8 of type II and III hernias. We used the laparoscopic Nissen procedure in
      all cases. There were no conversions to the open procedure. Hiatal hernia
      recurred only in one case with a short esophagus preoperatively. The laparoscopic
      Nissen procedure is here to stay for the repair of hiatal hernias regardless of
      their type.

PMID- 14574713
TI  - [Laparoscopic modified Girard myotomy and fundoplication for achalasia].
AB  - The standard surgical treatment for esophageal achalasia is improvement of the
      passage combined with antireflux repair. This paper describes the techniques of
      the laparoscopic modified Girard myotomy and fundoplication for achalasia. The
      laparoscopic modified Girard myotomy and fundoplication were performed through
      five upper abdominal trocars. A 10 cm myotomy extended 8 cm above the
      gastroesophageal junction and 2 cm below the gastroesophageal junction using an
      electric J-hook. Transverse sutures were placed on each side of the lower
      myotomy. The gastric fundus was covered with the upper myotomy with several
      sutures. Twenty-three patients were treated using this method. Excellent results
      were achieved. The laparoscopic modified Girard myotomy and fundoplication appear
      to provide effective treatment of achalasia with minimal invasion and rapid
      rehabilitation.

PMID- 14574712
TI  - [Surgery for benign submucosal tumors of the esophagus (leiomyoma and
      hemangioma)].
AB  - Among the submucosal tumors of the esophagus, leiomyoma is the most frequently
      found. Esophageal leiomyoma usually originates from the muscle layer of the
      esophageal wall and grows spirally around the esophageal axis. In the surgical
      treatment of leiomyoma, we enucleate the tumor through video-assisted thoracic
      surgery. When we enucleate leiomyoma, we must be very careful to aviod
      perforation of the esophageal mucosa. Esophageal hemangioma is a relatively rare
      disease. The location of this disease is mainly within the submucosal layer,
      without invading the muscle layer proper. After confirming the localization
      within the mucosa or submucosa with endoscopic ultrasonography, esophageal
      hemangioma can be resected safely using the endoscopic mucosal resection
      technique. In the treatment of benign esophageal submucosal tumors, "informed
      consent" is as essential as in esophageal cancer surgery. We have no absolute
      criteria concerning the indications for surgery for benign esophageal submucosal
      tumors. We must give reasons why the operation is necessary and indicated to the
      patients. Surgical treatment of esophageal submucosal tumors should be as
      minimally invasive as possible.

PMID- 14574714
TI  - [Esophageal diverticula].
AB  - Esophageal diverticula are considered to be rare but this has not deterred
      interest in the condition, either historically or in the present era. Most
      parabronchial esophageal diverticula are traction diverticula, and resection is
      thought to be unnecessary. The majority of pharyngoesophageal diverticula and
      epiphrenic diverticula are pulsion diverticula. It is now well accepted that they
      correlate with underlying motor disturbance and that surgery is indicated. If
      there is motor disturbance is preoperative manometry, it is necessary to add
      myotomy. However, if there is no motor disturbance, the surgical management
      remains controversial. Recently, minimal access surgery with laparoscopy or
      thoracoscopy has been successful in the treatment of epiphrenic diverticulum.

PMID- 14574715
TI  - [Etiology, diagnosis, and treatment of spontaneous esophageal rupture].
AB  - In some unique cases of idiopathic rupture of the esophagus where abscess is
      confined within the mediastinum and signs of infection are very slight, the
      patient's life can be saved with conservative treatment. However, because
      idiopathic esophageal rupture is related to vomiting in many cases, contamination
      of the mediastinum and thoracic cavity by vomit is severe, and prompt diagnosis
      and early surgery are crucial to save the patient's life. Gastrointestinal
      contents from idiopathic esophageal rupture pour out via the mediastinum from the
      bilateral sides of the vertebral body to form extrapleural abscess on the wall
      side. During observation, the abscess may sometimes enlarge, progress, and
      extend. Therefore, several computed tomography scans and ECHO need to be
      performed, followed by on-target drainage. Basically, idiopathic esophageal
      rupture cannot be cured by palliative treatment alone, and we need to undertake
      surgical treatment, as well as concomitant conservative treatments including
      blood purification (polymyxin, continuous hemodiafiltration), enteral feeding,
      and antibiotic therapy.

PMID- 14574716
TI  - [Surgery for disease of the esophagus. 8. Corrosive esophagitis].
AB  - After the ingestion of caustic substances, not only the esophagus but also the
      gastrointestinal tract is injured. Severe caustic upper gastrointestinal tract
      injuries are associated with high mortality and morbidity rates when
      mediastinitis, chemical peritonitis, or perforation of the gastrointestinal tract
      occurs. Perforation may occur in the late phase, especially with the ingestion of
      alkaline solution, because the inflammation invades more deeply with the
      continuous release of OH-after coming into contact with protein. Therefore care
      must be taken in the estimation of the extent of inflammation after the ingestion
      of caustic alkaline solution. There are on established indications for surgery in
      acute-phase corrosive esophagitis. At present, we determine the indications for
      surgery based on blood gas examination, endoscopy, and computed tomography (CT).
      Blood gas examination is used to diagnose the systemic status. Endoscopy reveals
      corrosive changes with mucosal injury, while CT reveals the presence of
      mediastinitis, chemical peritonitis, and gastrointestinal tract perforation in
      the acute phase. Patients in the acute phase first undergo limited resection of
      the injured organs without reconstruction, with secondary esophageal
      reconstruction performed subsequently. This paper reports on our successful
      experience in the early surgical treatment of patients who had severe tissue
      injury after the ingestion of caustic substances. Patient prognosis was good
      using our surgical technique.

PMID- 14574717
TI  - [Basic concepts and actions by the government for collecting information on
      medical adverse events to improve patient safety].

PMID- 14574718
TI  - [What we can learn from a case of medical malpractice].

PMID- 14574719
TI  - Thanatophobia revisited.

PMID- 14574720
TI  - More to it than meets the eye: dedicated membership.

PMID- 14574721
TI  - Loss prevention case of the month. Would guidelines have helped?

PMID- 14574722
TI  - Diabetic patient experiences in a Medicaid managed care system.
AB  - OBJECTIVE: When Tennessee received a federal waiver to place all Medicaid
      enrollees in managed care organizations (MCOs), patients with chronic conditions
      such as diabetes were deemed especially vulnerable. This survey assessed
      patients' perceptions of diabetic care, self-care procedures, and satisfaction
      with medical care before and after enrollment in a Medicaid MCO. METHODS: A
      telephone survey was designed and pilot tested before surveying 57 patients
      meeting inclusion criteria of continuous enrollment in Medicaid for two years
      before, and in the MCO for two years after, the initiation of Tennessee's
      Medicaid managed care system (TennCare). RESULTS: On average, patients were 56.1
      +/- 8.9 years old (mean +/- SD), African American (87.7%), female (73.7%),
      disabled (64.8%), with 8.4 +/- 2.8 years of education and annual incomes below
      $10,000 (54.4%). Mean age at diagnosis was 39.5 +/- 11.5 years, and most (75.5%)
      were currently prescribed insulin. Over one-third (39.6%) described the quality
      of healthcare received under managed care as excellent or very good and 38.9%
      felt prior Medicaid care was worse or much worse. Compared to Medicaid, patients
      reported no difference in being denied a test under managed care because of lack
      of approval (P = .754). However, significant improvements were reported in
      receiving detailed information about diabetes (89.5% vs. 73.7%, P = .022), and
      diet (89.5% vs. 77.2%, P = .039) for the TennCare period. Patients were more
      likely to perform finger stick blood glucose tests under the MCO (76.8% vs.
      40.7%, P = .001), but did not report that blood glucose was controlled more of
      the time (P = .332). CONCLUSION: Most patients were satisfied with their MCO
      care, and most reported that finger stick glucose monitoring increased under the
      MCO. However, no significant gains in controlling blood sugar were reported. From
      the perspective of most patients, enrollment in an MCO had positive outcomes and
      resulted in improved access to diabetes-related health information.

PMID- 14574723
TI  - Muscle injury associated with bupropion therapy.

PMID- 14574725
TI  - Tennessee's HIV Drug Assistance Program (HDAP).

PMID- 14574724
TI  - The death penalty for juvenile offenders.

PMID- 14574726
TI  - ER team pulls together to evaluate patients in 15 minutes.

PMID- 14574727
TI  - Minimize practice variation by focusing on 'top priority conditions'.
AB  - For years, physicians have debated--with each other and, increasingly, with
      health plans--the causes of variation in physician practice. Reducing variation
      has to be part of the institutional agenda. Plus, physicians should be given
      adequate resources to develop support systems that will enable them to deliver
      more consistent clinical practice.

PMID- 14574728
TI  - Multi-hospital information network improves care for uninsured.
AB  - When people come to a hospital's emergency department for treatment, they don't
      bring their medical records with them. That means physicians and nurses either
      have to spend valuable time looking for information on the patients, or they have
      to run diagnostic tests, which may duplicate tests that have already been done
      somewhere else. Four health care organizations in New Haven, CT, have developed a
      solution to improve electronic access to health records and reduce the expense of
      duplicate tests.

PMID- 14574729
TI  - Better communication expected to boost capacity at Sutter Medical Center.
AB  - If hospitals were run like motels, many would have 'no vacancy' signs out front
      these days. For a variety of reasons, most hospitals are operating near capacity.
      Of course, hospitals don't like to turn away patients, so they build new space
      and look for ways to get patients in and out faster. Sutter Medical Center in
      Sacramento, CA, thinks it has hit upon the answer with a computer system that
      automates the patient flow management process and makes communication between
      staff members more efficient.

PMID- 14574730
TI  - [Homocysteine metabolism and its role in pathology].
AB  - Results of the study of homocysteine metabolism and its role in physiological and
      pathological processes are given in this review. The participation of
      homocysteine in the process of methionine synthesis, transsulfuration, formation
      of homocysteine thiolacton and their regulation, polymorphism of homocysteine
      metabolism enzymes, the ways of homocysteine and thiolactone incorporation into
      protein molecule, sources and forms of homocysteine in the blood plasma, the role
      of hyperhomocysteinemia in pathogenesis of cardiovascular and other diseases have
      been considered. Principles of homocysteine determination in the blood plasma are
      described here.

PMID- 14574731
TI  - [Protein C system and thrombosis diseases].
AB  - The mechanism of protein C system functioning and role of its components in the
      regulation of the coagulation and the fibrinolysis was considered in the review.
      There are also new data about the anticoagulation, profibrinolysis and
      antiinflammatory functions of protein C system. Activated protein C is inhibited
      by the protein C inhibitor, alpha 1-antitripsin, and inhibitor of tissue
      activator plasminogen-1. Hereditary or acquired deficiency of protein C, protein
      S and thrombomodulin lead to thrombotic diseases. Injection of exogenous
      recombinant protein C or activated protein C into the blood increases the
      anticoagulant activity of the blood and produced the antithrombotic effect.

PMID- 14574732
TI  - [Recombination in Escherichia coli cells and multiform cytotoxic resistance].
AB  - Genetic crosses between E. coli Hfr C--donor and E. coli AB 1157--recipient cells
      sensitive to single target inhibitor glyphosate gave rise to offspring which
      could tolerate not only minimal inhibitory concentration of this inhibitor but
      also six-fold increased concentrations. No change in glyphosate target enzyme
      activity in transconjugants (resulted from recombination occurred at arg G and
      proAB genome regions, respectively) compared to that of parent strains was
      observed. If new combinations due to recombination of some genetic factors is
      responsible for emergence of this resistance the question is raised on the nature
      of these factors and their role in cell biology.

PMID- 14574733
TI  - [Estradiol-17beta activates corticosteroid synthesis and inhibits proliferation
      in cultured porcine adrenocortical cells].
AB  - The influence of estradiol-17 beta on corticosteroids production and cell
      proliferation were studied in the cultured pig adrenocortical cells. Estradiol-17
      beta considerably increased steroidogenesis, but inhibited cell proliferation. It
      is speculated, that cAMP mediated estradiol-17 beta effects in the adrenal cells.

PMID- 14574734
TI  - [Correlative links between superoxide dismutase, catalase and glutathione
      peroxidase activities in mouse liver].
AB  - Qualitative and quantitative differences in correlative and regressive links
      between superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase
      were assessed in the mice liver by two- and three-dimensional statistical
      methods. Paired linear correlation analysis indicated SOD-CAT tandem as the
      correlatively acting enzymatic pair. Three-dimensional analysis revealed uniform
      response surfaces which exhibited higher activities at disproportional values of
      the other two and lower activities at proportional activities of the other two
      enzymes. The direct effect of the enzymes on each other was positive [table: see
      text] while the effect of their product was always negative.

PMID- 14574736
TI  - Specific interaction of isocytosine and amino acid carboxylic group shifts the
      base tautomeric equilibrium.
AB  - By 1H NMR, UV and IR spectroscopies in anhydrous DMSO and quantum-chemical
      calculations by MNDO/H in vacuum specific interactions of isocytosine with
      neutral and deprotonated carboxylic groups of amino acids were investigated. In
      vacuum interaction with carboxylate ion provokes in isoCyt transition from the
      ground-state enolic form to the high energy N3H-keto tautomer. In DMSO keto
      tautomer N3H of isoCyt is stabilized but interactions with carboxylate ion
      essentially shifts equilibrium to enolic form. Neutral carboxylic group forms the
      most stable complex with the ground-state enolic tautomer in vacuum but in DMSO
      it proves to shift the keto(N3H)-enolic equilibrium to the right.

PMID- 14574735
TI  - [Ubiquinone content and function in the mitochondrial electron transport chain in
      experimental focal myocarditis in rats].
AB  - The content of ubiquinone and vitamin E and functioning of ubiquinone-dependent
      enzyme systems in myocardial mitochondria and blood leucocytes of rats under
      experimental microfocal myocard damage, and the effect of vitamin E under given
      pathology have been studied. Direct dependence between the content of ubiquinone,
      vitamin E and activity of succinateubiquinone reductase system of blood
      leucocytes has been established. Vitamin E demonstrates the normalizing effect on
      the subjects of our study.

PMID- 14574737
TI  - [Activity of dsRNA-dependent protein kinase in rat lymphoid cells under the
      effect of X-ray irradiation].
AB  - The activity of dsRNA-dependent protein kinase, which is the key enzyme of the
      interferon signal system, was studied in the rat spleen and thymus lymphocytes
      under the influence of X-ray irradiation at 0.5 and 1 Gy doses and interferon
      inducers administration. An increase of the enzyme activity was established in
      the presence of FGA, concanavaline A, poly(I).poly(C) in vitro. The effect is
      intensified under the irradiation by 0.5 Gy dose. The protein kinase activity in
      lymphocytes is amplified in proportion to poly(I).poly(C) concentration, that was
      most pronounced in the irradiated animals. The comparative analysis of the action
      of interferon inducers on the dsRNA-dependent protein kinase activity was carried
      out. Two biological systems were used: in vivo (when the preparations were
      injected to the experimental animals) and in vivo (under the preincubation of
      isolated lymphocytes with the inducers). It was shown that the combined action of
      radiation and interferon inducers causes the stimulation of dsRNA-dependent
      protein kinase activity.

PMID- 14574738
TI  - [Effect of forskolin and quinacrine on leukocyte functions under the effect of
      low-dose radiation].
AB  - The adenylate cyclase and phospholipase A2 incorporation in the functional
      responses as well as lipid peroxidation processes and glutathione system
      homeostasis of animal leukocytes to small doses of ionizing radiation (1-100 mGy)
      have been estimated. The cells were irradiated by introduction of radioactive
      isotope 14C-leucine into the incubation medium. It is established that the
      ionizing radiation has different effects on the modification of cellular
      functions by the agents, which change adenylate cyclase and phospholipase A2
      activity. Neutralization of stimulative irradiation effect on chemokinesis of
      polymorphonuclear leukocytes by quinacrine (the inhibitor of phospholipase A2)
      indicates for certain, that metabolism of eicosanoids takes immediate part in the
      cell response to ionizing radiation. Apparently, adenylate cyclase has no
      influence on this process, where at indicates the lack of influence of forskolin
      (the stimulator of adenylate cyclase) on the spontaneous motility, and on the
      radiation action on this leukocyte function. Rosette forming ability of
      lymphocytes is regulated by both enzymes because it is modified both by the
      inhibitor of phospholipase A2, and by the adenylate cyclase stimulant. In this
      case it is impossible to exclude the action of ionizing radiation both through
      the adenylate cyclase cascade, and through the eicosanoid metabolism. In all the
      concentration range the radionuclides do not affect the studied biochemical
      indexes of the cell, but change the action of the modifiers.

PMID- 14574739
TI  - [Regulation of Ca(2+)-binding properties of calmodulin nitrite-anion and hydrogen
      peroxide].
AB  - The effect of NO2- and H2O2 on Ca(2+)-binding properties of calmodulin has been
      studied. The decrease of Ca2+ affinity for calmodulin and limiting quantity of
      the sites of cation cross-linking by the protein molecule under the effect of 1
      nM NO2 and 10 nM H2O2. The increase of the acting substances concentration above
      physiological one results in the considerable decrease of the observed effects.
      The investigation results indicate to possible inhibition of Ca(2+)-calmodulin
      dependent cytosole reaction of the smooth-muscle cells under the effect of NO2
      and H2O2, and this will result in the myometrium relaxation. At the same time the
      data from literature and results of the authors' experiments allow supposing the
      difference in the mechanisms of NO2 and H2O2 actions on these processes.

PMID- 14574740
TI  - [Antioxidant properties of rhenium cluster complexes with butyric acid
      derivatives in blood plasma and erythrocytes].
AB  - The antioxidant action of rhenium cluster complexes with isobutiric and gamma
      aminobutiric acids were studied in vitro. It was established that strong
      antiradical properties were found in the reaction with stable radical
      diphenylpycrylhydrazile Re2(i-C3H7COO)4Cl2, [Re2(GABA)2Cl5(H2O)]Cl.2H2O. The
      chemiluminescence investigation of antioxidant properties of both substances
      Re2(i-C3H7COO)4Cl2 and [Re2(GABA)2Cl5(H2O)]Cl.2H2O has established that these
      properties are realized in the blood plasma and erythrocytes, but to different
      extent.

PMID- 14574741
TI  - [Nature and store of fatty acid lipids in the blood of newborn calves with
      dyspepsia].
AB  - The content of fatty acids of lipids extracted from the whole blood as well as
      from erythrocytes, leucocytes, plasma and serum samples of newborn dyspeptic
      calves were investigated for the first time. Twenty three (23) saturated, mono
      non-saturated and poly-non-saturated fatty acids were detected. Native,
      palmitoleic, stearic, oleic, linoleic and arachidonic fatty acids, are the main
      components of the whole blood lipid fraction and its components. The fatty acids
      found in lipids and other components of the whole blood in the samples of
      dyspeptic and healthy calves are the same, their ratios, however, are different.
      The decrease in the nonsaturated fatty acids content and its increase in
      saturated fatty acids are considerable. The saturation coefficient is different
      in native blood lipids, erythrocytes, leukocytes, serum and plasma.

PMID- 14574743
TI  - [Effect of zinc ions, manganese and lead ions on the thermostable proteins of
      carp liver].
AB  - Effect of comparatively low concentration of the zinc, manganese, lead ions (0.1,
      0.13 and 0.01 mg/l respectively) on the thermostable proteins (TP) of the carp
      liver after fish incubation for 14 days was studied. It is revealed that about 30
      of zinc, 40% of manganese and 6% of lead were bound in the TP solution. The
      results of chromatography on Sephadex G-75 show, that the metallothionein-like
      proteins (MT, M-6 kDa) were the primary metal-binding proteins among the TP for
      zinc and manganese, and the heavy fraction of TP (M-60 kDa)--for lead. Under the
      action of each of the metallions its content in the TP is significantly
      increased. The distribution of metals among TP compounds is similar to that in
      the control. The metals action causes specific changes of the heavy fraction
      properties (UV spectrum, SH-groups content). The properties of MT do not change
      significantly under the control value.

PMID- 14574742
TI  - [Comparative study of the effect of alpha-tocopherol, its synthetic metabolite
      and ionol on dexamethasone-induced apoptosis in rat thymocytes].
AB  - alpha-Tocopherol was found to decrease the level of rat thymocytes DNA
      fragmentation and to increase the viability of these cells under apoptosis
      induction by dexamethazone. So the antiapoptotic role of this vitamin is
      suggested. In contrast to alpha-tocopherol synthetic antioxidant ionol and alpha
      tocopherylacetate, contained only 6 carbon atoms in its isoprenoid side chain
      caused the cell death from necrosis. This process preceded the apoptosis
      stimulated by dexamethazone.

PMID- 14574744
TI  - [Mechanism of action of a novel antitumor preparation of chlofiden. Effect on RNA
      synthesis].
AB  - Study of the influence of the antitumor preparation chlofiden on RNA synthesis by
      sarcoma 45 and liver cells was carried out using 14C-orotic acid. Chlofiden was
      shown to activate RNA transport from the nucleus to the cytoplasm, and to reduce
      label incorporation into the nuclear and cytoplasmic RNA. Chlofiden increased the
      rate of RNA processes, which promoted some increase of label incorporation into
      low molecular RNA fraction of the nucleus and the cytoplasm. High and stable
      antitumor activity of chlofiden on sarcoma 45 was established.

PMID- 14574745
TI  - [Fatty acid composition of apical and basolateral enterocyte membranes of the
      small intestine of the gopher].
AB  - Fatty acid composition of gopher's (Citellus suslicus G.) small intestine apical
      and basolateral membranes of enterocytes has been investigated. The content of
      eight fatty acids: C12:0, C14:0, C15:0, C16:0, C17:0, C18:0, C16:1, C18:1 has
      been obtained.

PMID- 14574746
TI  - [Changes of mitochondrial oxidation and phosphorylation in the testes of white
      rats under excessive supply of sodium nitrate into the organism].
AB  - The functional state of mitochondria, obtained from the testicles, after chronic
      intoxication by sodium nitrate (in a dose of 200 mg/kg during 14; 30 and 90 days)
      was investigated in experiment on white rats. It was revealed, that in dynamics
      of changes of mitochondrial oxidation and phosphorylation in the testicles under
      the excessive supply of sodium nitrate into the organism the determined phases
      should be marked: on the 14th day of intoxication this is the ascending of rate
      of respiration, on the 30th and 90th day--separation of the mitochondrial
      oxidation and ADP phosphorylation. It is supposed, that in pathogenesis of these
      changes the essential role belongs to nitric oxide production.

PMID- 14574747
TI  - [Activity of Ca(2+)-dependent neutral proteinases in rat organs under cobalt and
      mercury chloride injection].
AB  - The activity of Ca(2+)-dependent neutral proteinases in rats under cobalt and
      mercury chloride injection was investigated. The calpains activity increase in
      the lungs, heart, liver and kidneys was revealed after 2 h cobalt chloride
      action. The mercury chloride gives a reliable increase of calcium-dependent
      neutral proteinases only in the kidneys.

PMID- 14574748
TI  - Determination of the binding parameters for a pre-existing antigen-antibody
      mixture.
AB  - A new method, which allows to evaluate parameters of interaction between
      antibodies (or receptors) and an antigen (or ligand) is suggested. The method is
      based on the use of so-called coordinates of dilution suggested by the author
      earlier. Representation of the data of the titration curves for the mixtures of
      antibodies (or receptors) and antigen (or ligand) in these coordinates allows one
      to determine the affinity of interaction and the concentration of antigen (or
      ligand), which can reversibly block antibodies (or receptors). Simple formulas,
      which allow to estimate which part of paratopes or bivalent antibodies is free
      and which part is blocked by the antigen, depending on dilution of the considered
      system, are also suggested. Such a method could be useful for characterization of
      infection and autoimmune processes when the antigen and antibodies circulate
      together in the bloodstream.

PMID- 14574749
TI  - [Prions and protein inhibitors of proteinases: structural analogies and their
      consequences. IV. The nature of the interspecies barrier of prion disease].
AB  - Declining of unproved supposition about the transformation of the cellular
      isoform of prion protein into pathogenic one allows the pathogenesis of prion
      diseases to be reduced to the series of interdependent processes caused by prion
      mediated selective damage of the components of the cell chaperoning system with
      following membrane folding of the de novo synthesized prion protein. Dependence
      of the level of the cell chaperoning system damage on the similarity of the
      sequences of cellular and infectious prion proteins explains exhaustively the
      existence of interspecies barrier in prion pathogenesis as well as makes it
      natural and inevitable property of the latter. The structural ensurance of
      separate prion diseases strains, their transformation at repeated infectious
      passages commonly with known and supposed ways for prion-less initiation of
      spongiform encephalopathies are discussed.

PMID- 14574750
TI  - [Hyperhomocysteinemia in acute cerebral infarction].
AB  - ANTECEDENTS: Hyperhomocysteinemia has recently been recognized as contributing
      directly or associatively to the arteriosclerotic process in cerebral infarction.
      OBJECTIVE: To determine plasmatic homocysteine levels in with patients with acute
      cerebral infarction and to seek an association between clinical sub-types of
      cerebral lesion and homocysteine levels and risk factors present. MATERIALS AND
      METHODS: A descriptive study was carried out on patients diagnosed with acute
      cerebral infarction. The study included 22 patients of both sexes between the
      ages of 40 and 85 years. Samples were collected on the second day of
      hospitalization after 12 h of fasting. RESULTS: In 13 of 22 patients, elevated
      levels of serum homocysteine were found. The homocysteine average was 20-68
      mumol/l +/- 9.6 SD. No association between degree of cerebral lesion and risk
      factors was found (p > 0.05). CONCLUSION: An increase in homocysteine was found
      in 59% of cerebral infarction patients. No correlation between
      hyperhomocysteinemia and known risk factors such as smoking, alcoholism, high
      blood pressure, and diabetes was found. It is necessary to continue this line of
      investigation to identify conditioning factors that elevate homocysteine and to
      implement measures to lower levels of hyperhomocysteinemia, thus helping reduce
      the incidence of cerebrovascular disease.

PMID- 14574751
TI  - [Comparative study of the application of a diagnostic test in postgraduate
      education, using 2 formats: computerized and printed].
AB  - A diagnostic test was applied at the National Autonomous University of Mexico
      School of Medicine using a two-part format with 42 clinical cases and 210
      multiple-choice items. Residents were randomized into two groups: group A
      (printed test) and group B (computerized test). Academic performance was measured
      by determination of media, standard deviation, and correct-answer score; the exam
      was measured by reliability, difficulty index, and discrimination index and
      question/item assessment were calculated for item analysis. Residents answered a
      survey questionnaire and time taken to answer was controlled. Results showed that
      the printed test had higher achievement; there was better reliability for
      computerized format, and resident opinion was more favorable toward computer use.
      The two parts of the test were analyzed and results were produced for the first
      part of the test; in part two, results were very similar. We conclude that lack
      of experience in computer use could be a determining factor in our results.

PMID- 14574752
TI  - [Rattlesnake bite poisoning, health damage and treatment in children].
AB  - INTRODUCTION: In Mexico, we do not know the exact number of cases and the
      magnitude of health damage conditioned by poisonous rattlesnake bites, and little
      relative information exists in pediatric population. OBJECTIVE: To inform on
      continued follow-up of 55 patients at a children's hospital, and to propose a
      therapeutic sequence adequate for children. MATERIALS AND METHODS: We reviewed
      clinical records and variables were origin, age, sex, time of year, previous care
      measures, time passed, hospital treatment complications and care cost. RESULTS:
      Rattlesnake bite occurred around the home at times and at times inside the home
      in rural areas; we did not observe any noticeable difference in gender; snake
      variety most involved was Crotalus atrox, anatomic site most injured were the
      lower extremities in 78%. Prior to admission, 50% received insufficient antivenom
      serum doses; the most frequent complication was hematologic in 69%. One patient
      died with multiple organ failure and disseminated intravascular coagulation
      (DIC). The treatment protocol that we have recommended since 1986 at the Hospital
      Infantil del Estado de Sonora, revised and modified in 1996, reduced hospital
      stay from 15 to 5 days. CONCLUSION: The protocol used avoided further
      complications and had a favorable influence on cost reduction.

PMID- 14574753
TI  - [Trends of 6 primary causes of mortality in Mexican children in 1971-2000.
      Epidemiologic transition in children].
AB  - OBJECTIVE: To determine trends of six main causes of mortality in Mexican
      children < 15 years of age. MATERIAL AND METHODS:  TYPE OF STUDY: Observational,
      descriptive and retrospective. STUDY PERIOD: January 1, 1971 to December 31,
      2000. Studied Population: Children < 15 years of age, Statistic Analysis:
      mortality rates were obtained due to perinatal causes, respiratory infections,
      intestinal infections, accidents, congenital malformations (CM), and cancer (CA).
      They were stratified according to age groups in < 1 year, 1 to 4 years, 5 to 14
      years, and 1 to 14 years of age. Percentage differences were calculated between
      1971 and 2000, as were respective trends. RESULTS: Global decrease in mortality
      was according to age group, 83.5% in 0 to 14-year-old, 71.3% in under one year
      old, 90.5 in 1 to 4-years-old, 79.2% in 5 to 14-year-old. The largest decrease in
      all groups was observed for infectious causes (> 90%), and increased CM between
      120.1 to 160.5%, and CA between 28.0 to 56.4%. CONCLUSIONS: Mortality in Mexican
      children has decreased significantly. Infectious causes show the most important
      reduction, the CM and CA showing largest increase. Accidents, although they
      reveal some tendency to decrease, are first cause of death in the group 1 to 14
      years of age. Present data indicate the need to continue programs to provide care
      for infections diseases, and to establish new programs that include care for
      accidents, CM, and CA in children.

PMID- 14574754
TI  - [Facing the challenge... Towards a National Program of Adolescence Health Care in
      Mexico, 2001-2006].
AB  - OBJECTIVE: To present the process in the design, development and implementation
      of Mexico's National Adolescent Health Program. MATERIALS AND METHODS: In efforts
      to arrive at a consensus regarding the health care priorities for Mexico's
      adolescent population, 37 public and private institutions dedicated to adolescent
      health care and social issues were invited to participate in a strategic analysis
      regarding a joint action plan for health promotion in adolescents with special
      emphasis on resilience as protective factor. The definition of the action plan
      involved the participation of 190 health professionals responsible for child and
      adolescent health programs in the discussion and drafting of the National Health
      Program. RESULTS: The steps and issues discussed by the 37 participating
      institutions leading to the development of the National Health Plan are reviewed.
      CONCLUSIONS: The product of this exercise led to the elaboration of a consensus
      document that served as the framework for Mexico's National Adolescent Health
      Plan and that now serves 23.5 million adolescents between 10 and 19 years of age.
      This action plan was been reviewed by the World Health Organization, which cited
      Mexico as one of the eight model countries addressing adolescent health.

PMID- 14574755
TI  - [Testicular necrosis resulting from torsion in children. Perspective of a second
      level hospital].
AB  - INTRODUCTION: The disaster of a testicular torsion leading to the possible loss
      of a gonad within a few hours is a well known occurrence and it is discouraging.
      Clinical examples emphasizing torsion of the testis as the most important
      differential diagnosis in children with acute scrotal pain and swelling, as well
      as the need for early exploration, have been reported with increasing frequency.
      MATERIAL AND METHODS: Seventy cases of clinically diagnosed unilateral torsion of
      the testis have been admitted to our pediatric surgical unit over a period of 8
      years. There were 46 cases between 13 and 15 years of age; 34 were admitted after
      24 ho and 25 after 3 days of multilating disease. Left side was involved in 46
      cases and 61 testicles were removed. CONCLUSIONS: In order to avoid initiation
      procedures, early diagnosis is very important.

PMID- 14574756
TI  - [Domestic violence].

PMID- 14574757
TI  - [Migraine. Review of physiopathogeny and future alternative therapy].
AB  - This work examines recent discoveries in physiopathogenesis, focusing on the
      combination of sequential events involved in migraine origin. Recent facts
      concerning active intestinal peptide, substance P, histamine, HI and H3
      receptors, and H3-receptor agonists, all neuromodulators having an intimate
      relations ship with migraine were examined. Present-day recommended treatment,
      with an efficacy of barely 70%, and reasons for its poor performance were
      described. The authors state that the future of migraine treatment should be
      directed toward the search for drugs that directly interact with the above
      mentioned neuromodulators, thus offering patients a more efficacious treatment
      and fewer undesirable side-effects.

PMID- 14574758
TI  - [17-year-old woman with mouth and genital ulcers, and hemoptysis].

PMID- 14574759
TI  - [Ureteral inflammatory pseudotumor].

PMID- 14574760
TI  - [Trans-septal puncture for radiofrequency ablation of left accessory pathway].
AB  - We present the case of an 18-year-old male patient with diagnosis of Wolff
      Parkinson-White syndrome due to a left free wall accessory pathway. We performed
      an electrophysiology study and transseptal punction guided by transesophageal
      echocardiogram to via access to the left atrium. We performed successful
      radiofrequency ablation of the accessory pathway, observing disappearance of the
      delta wave on the first attempt. There were no complications. In follow-up a 10
      months, the patient had no clinical nor electrocardiographic evidence of
      recurrence. Transseptal radiofrequency ablation is an alternative for treatment
      of some arrhythmias localized in the left side of the heart.

PMID- 14574761
TI  - [Scientific controversy at the National Academy of Medicine: a view from
      history].
AB  - This essay deals with two scientific discussions that occurred at the National
      Academy of Medicine, one in the 19th century and the other, in the 20th century.
      Our goal was to emphasize that the National Academy of Medicine offers the space
      for scientific discussion related to medical problems.

PMID- 14574762
TI  - [The venerable Varon Gregorio Lopez, impact of his life and work throughout 400
      years, 1562-2000].
AB  - During the second half of the 16th century in New Spain, there was a peculiar but
      versatile man named Gregorio Lopez whose ascetic lifestyle, remarkable erudition
      and talent granted him an important place in history to date. The aim of this
      work was to focus attention on two aspects that have been ignored by contemporary
      historians. On the one hand, we will refer to Lopez's medical works, known as
      Tesoro de Medicinas (A Treasure of Medicines), a piece that although it is still
      immersed within the hypocraticgalenic tradition, continues to be highly valued.
      On the other hand, we found a vast amount of historiographic works that support
      the case for his beautification that began just 24 years after his death in 1596.
      The contribution we now make is divided into two parts for better understanding
      of the subject. We must emphasize, however, that both the exciting life this
      "Venerable Man" (Venerable Varon) led and the repercussions his deeds had,
      demonstrate an extraordinary coherence between the learned and the mystical man
      that he was. Gregorio Lopez always maintained a remarkable social and religious
      presence, not only throughout the three centuries of colonial rule in Mexico, but
      also during the subsequent two hundred years that followed the struggle for
      Independence.

PMID- 14574763
TI  - [Segmental dilatation of the colon].

PMID- 14574764
TI  - [Usefulness of molecular biology techniques in the diagnosis of fragile X
      syndrome].

PMID- 14574765
TI  - [The Nazis, guide of the International Conference of Harmonization and ethics
      committees].
AB  - This article begins with the basic ethical principles in clinical research. The
      four moral principles of autonomy, beneficence, non-maleficence, and justice are
      reviewed. Likewise, a historical review of the participation of German physicians
      and the medical establishment that carried out the policies of the Third Reich is
      examined, and delineates several moral failures attributable to these physicians
      during the dark period of history known as the Holocaust. Medical ethics were
      completely ignored during that period, and thus, the Nuremberg Code was enacted
      for regulating human research by means of informed consent. A historical vision
      of the universal documents for ethics in clinical research has been reviewed from
      the Declaration of Helsinki in 1964 to the ICH Guideline (International
      Conference of Harmonisation) for Good Clinical Practice (GCP) in 1996. The ICH
      Guideline is an international ethical and scientific quality standard for
      designing, conducting, recording, and reporting trials that involve participation
      of human subjects. The guide was developed with consideration of the current GCP
      of the European Union, Japan, and the U.S. Finally, we establish the composition,
      functions, and operations of the Ethic Committees that ensure the rights, safety,
      well-being, and confidentiality statement of subjects who participate in clinical
      research studies and document that protection by reviewing and
      approving/rejecting a study protocol, and evaluate research personnel, the
      research site, and materials and methods used for obtaining and recording
      informed consent protocol from subjects participating in the study.

PMID- 14574766
TI  - [Legal aspects of cases of blood transfusion in Jehovah's Witnesses].

PMID- 14574767
TI  - [In reference to the article "Reflections on the Bristol case and medical care in
      Mexico"].

PMID- 14574768
TI  - Frequency of congenital dyschromatopsias in male population of the Split
      Dalmatian County in Croatia.
AB  - A population of 9974 healthy male subjects (aged 15-45 years) was screened for
      congenital dyschromatopsia. The study group consisted of subjects applying for a
      driving license in the Split-Dalmatian County between 1996 and 1999. The aim was
      to establish colour vision deficiency (dichromats) and borderline deficiencies
      (anomalous trichromats) in candidates through complete ophthalmologic examination
      including the Ishihara pseudoisocromatic plates, anomaloscope Nagel II, and Hue
      Lanthony colour test. The frequency of congenital dyschromatopsias was 8.48%.
      This frequency includes 2.39% dichromats (1.49% protanops and 0.90% deuteranopes)
      and 6.09% anomalous trichromats (1.27% protanomals, 4.20% deuteranomals, 0.21%
      extreme protanomals and 0.41% extreme deuteranomals). It is important to
      recognise and classify dyschromatopsias according to type and severity in order
      to avoid misinterpretation of results and consequent unjustified limitations
      imposed on anomalous trichromats in the selection of a profession.

PMID- 14574769
TI  - [Effect of age on asbestosis of the lung and/or pleura].
AB  - This study included 97 subjects with parenchymal and/or pleural asbestosis and
      100 controls. Data analysis included medical and work histories, X-ray clinical
      examination, and the measurement/calculation of ventilatory lung functions VC,
      FVC, FEV1,FEV1/VC and FEV1/FVC. Of 97 subjects with asbestosis, 30 (31%) were
      diagnosed parenchymal fibrosis, 33 (34%) pleural fibrosis, and 34 (35%)
      parenchymal and pleural fibrosis combined. These subgroups did not differ in
      smoking habit. All subjects with asbestosis showed symptoms of dyspnoea; two
      thirds showed dyspnoea on exercise and one third at rest as well. In contrast,
      only one third of controls showed dyspnoea on exercise only. All ventilatory lung
      functions were lower in subjects with asbestosis than in controls (P < 0.01),
      except for FEV1/FVC (P > 0.05). Slight, yet clinically significant drops in
      ventilatory function were observed in subjects with pleural (VC 79.73%; FVC
      75.09%; and FEV1 78.52%) and combined asbestosis (VC 78.21%; FVC 75.01%; and FEV1
      77.50%), while ventilatory changes in subjects with parenchymal asbestosis were
      clinically significant only for FVC (79.60%). It was not possible to discriminate
      between the effects of age and exposure duration in subjects with pleural and
      combined asbestosis.

PMID- 14574770
TI  - [The black widow spider--its appearance and control].
AB  - Between 1995 and 2002, a massive appearance of black widow (Latrodectus mactans
      tredecimguttatus, Rossi 1790) was recorded along the Croatia coast. This paper
      gives a historical review of latrodectism and observations from Istria and
      Dalmatia, paying particular attention to the spider's habitat. There are several
      reasons for the black widow to appear in a new habitat such as the introduction
      of leguminous plants, watermelons and melons where crops were grown earlier.
      Black widow can also be found near buildings and gardens. Human contacts with the
      spider are usually without consequences for humans, thanks to education and a
      relatively good visibility of the spider. The authors describe their experience
      in fighting black widow and emphasise the importance of education in preventing
      lactrodectism.

PMID- 14574771
TI  - [Matrix-assisted laser desorption ionization].
AB  - Since its invention, matrix-assisted laser desorption ionization (MALDI) has
      found wide application in mass spectrometry of high molecular weight compounds
      such as synthetic polymers and biopolymers. Despite widespread application of
      MALDI, the fundamental processes of ion formation and desorption are still poorly
      understood. The chemistry of the MALDI process, occurring both during sample
      preparation and during ionization is reflected in the mass spectrum. As the MALDI
      technique now stands a low concentration of analyte molecules, which usually
      exhibit only moderate absorption per molecules, is embedded in matrix crystals
      consisting of a small, highly absorbing species. In this manner the efficient and
      controllable energy transfer is retained while the analyte molecules are
      separated from excessive energy that would lead to their decomposition. The
      matrix is believed to serve two major functions: adsorption of energy from the
      laser light and the isolation of analyte molecules from each other. There are 3
      major methods for the preparation of samples for analysis which are quite quick
      and simple: dried droplet, surface and sandwich preparation. Experiments with pH
      indicator dyes serve as proof that analyte's charge state in the matrix crystals
      is the same as in solution. Upon laser desorption a sudden and explosive phase
      transition occurs and a dense plume of desorbed material is formed. The initial
      velocity of analyte ions in the plume depends only on the matrix used. Initial
      species formed as a result of laser desorption are tiny clusters. They consist of
      a matrix, analyte and other ionic species embedded in the matrix crystals all
      held together by hydrogen bonds and coulombic interactions. The first essential
      charging and thus ionization process is the statistical occurrence of clusters
      with a deficit/excess of anions of cations. Very small initial clusters are
      likely to be highly charged. Highly charged initial clusters cannot survive in
      the matrix plume and their charge drops. Clusters shrink by evaporation of
      neutral molecules. This paper presents only those cases leading to analyte ions
      and compares MALDI and the electrospray ionization technique.

PMID- 14574772
TI  - [Biological and toxin terrorism weapons].
AB  - The use of biological agents and toxins in warfare and terrorism has a long
      history. Human, animal and plant pathogens and toxins can cause disease and can
      be used as a threat to humans, animals and staple crops. The same is true for
      biological agents. Although the use of biological agents and toxins in military
      conflicts has been a concern of military communities for many years, several
      recent events have increased the awareness of terrorist use of these weapons
      against civilian population. A Mass Casualty Biological (Toxin) Weapon (MCBTW) is
      any biological and toxin weapon capable of causing death or disease on a large
      scale, such that the military or civilian infrastructure of the state or
      organization being attacked is overwhelmed. A militarily significant (or
      terrorist) weapon is any weapon capable of affecting, directly or indirectly,
      that is physically or psychologically, the outcome of a military operation.
      Although many biological agents such as toxins and bioregulators can be used to
      cause diseases, there are only a few that can truly threaten civilian populations
      on a large scale. Bioregulators or modulators are biochemical compounds, such as
      peptides, that occur naturally in organisms. They are new class of weapons that
      can damage nervous system, alter moods, trigger psychological changes and kill.
      The potential military or terrorist use of bioregulators is similar to that of
      toxins. Some of these compounds are several hundred times more potent than
      traditional chemical warfare agents. Important features and military advantages
      of new bioregulators are novel sites of toxic action; rapid and specific effects;
      penetration of protective filters and equipment, and militarily effective
      physical incapacitation. This overview of biological agents and toxins is largely
      intended to help healthcare providers on all levels to make decisions in
      protecting general population from these agents.

PMID- 14574774
TI  - [Classical monoamine oxidase inhibitor: not registered for, but still a place in
      the treatment of depression].
AB  - In the Netherlands monoamine oxidase (MAO) inhibitors are not registered for the
      treatment of patients with depression. The classical, nonselective MAO inhibitors
      -phenelzine and tranylcypromine--are effective but their use is associated with
      interactions (with tyramine in food, sympathicomimetics and serotonine re-uptake
      inhibitors) and side-effects (hypertension, hypotension, headache, sleep
      disturbances and neuromuscular symptoms in particular). Therefore, the classical
      MAO inhibitors are indicated only in depressive disorders that are unresponsive
      to the first stages of treatment. Taking this selection into account, treatment
      should be long-term to avoid relapse.

PMID- 14574773
TI  - [Elderly patients, classical monoamine oxidase inhibitors and intercurrent
      somatic diseases].
AB  - Three patients, a woman aged 70, a man aged 74 and a woman aged 78 years, all
      using tranylcypromine, a monoamine oxidase inhibitor (MAOI), to prevent the
      recurrence of severe depressive disorders, developed an intercurrent somatic
      disease. On admission to a general hospital, the first patient was initially
      refused her MAOI. The second patient was twice refused anaesthesia and the
      depression recurred twice when the MAOI was tapered off in connection with his
      operation. Both recovered after being given tranylcypromine. The third patient
      received tramadol from her surgeon and read in the directions for use that this
      drug should not be combined with a MAOI. After discontinuation of the MAOI the
      depression recurred, her medical condition deteriorated and she died. MAOIs are
      often a treatment of last resort. Discontinuation of an effective treatment and
      hence compromising the patient's psychiatric status increases the risk of medical
      and psychiatric complications and therefore should be avoided. Interdisciplinary
      consultation is essential in such cases.

PMID- 14574775
TI  - [The practice guideline 'Anemia' from the Dutch College of General Practitioners;
      a response from the perspective of general practice medicine].
AB  - The practice guideline 'Anaemia' from the Dutch College of General Practitioners
      will certainly be a support for the Dutch general practitioner. The inclusion of
      an algorithm to make a more precise diagnosis is an experiment that needs to be
      evaluated in the near future. However, many general practitioners will regard it
      as too complex for use in daily practice and specialists will find it to be of
      limited use, as it does not cover all cases. Consultation between the general
      practitioner and the specialist will give the best answer in complicated cases.
      Patients who complain about tiredness or dizziness will expect their general
      practitioner to take a blood sample for a haemoglobin test. The general
      practitioner will consider the risk of false-positive test results in
      interpreting the patient's haemoglobin level. A few concrete remarks: the
      guideline does not mention that vegetarianism and a low meat intake can increase
      the risk of vitamin B12 deficiency, and iron suppletion is advised in
      premenopausal women with profuse vaginal blood loss, whereas there are several
      treatable disorders that may cause menorrhagia.

PMID- 14574776
TI  - [The practice guideline 'Anemia' from the Dutch College of General Practitioners;
      a response from the perspective of internal medicine].
AB  - Anaemia is a prevalent condition that becomes more common with age. The Dutch
      College of General Practitioners has issued a guideline entitled 'Anaemia' which
      is aimed at standardizing the diagnostic approach to the anaemic patient. Much
      attention is paid to iron deficiency anaemia and anaemia accompanying chronic
      disease. The guideline stresses the need for careful analysis of iron deficiency,
      especially in the elderly. Unfortunately, the proposed algorithm is incomplete
      and not unequivocal. This will hamper its application in daily practice.

PMID- 14574777
TI  - [Fitness-to-drive in neurological disorders].
AB  - Driving-license holders with health problems are morally obliged to report this
      to the Driver Licensing Centre (CBR). The CBR can then further investigate the
      matter and either insist that technical modifications be made to the vehicle or
      declare the driver (temporarily) unfit to drive a vehicle. After an epileptic
      seizure a driver may not drive a car or ride a motorcycle for six months.
      Following multiple seizures this period is extended to one year after the last
      seizure. Exceptions can be made only if certain established criteria are
      fulfilled. Following cerebral infarction or cerebral haemorrhage, the driving
      license holder is considered unfit to drive for at least six months. After this
      period fitness-to-drive is dependent on the presence of any disorders of function
      and the results of a CBR driving test. Persons with an intracranial tumour are
      assessed on the presence of any disorders of function and may be given a driving
      license valid for a limited period of time only. A transient ischaemic attack
      (TIA) or the chance discovery of an unruptured intracranial aneurysm or vascular
      malformation which does not need treatment, does not necessarily affect fitness
      to drive. Persons with syncope, progressive neurological disorders or stationary
      functional disorders should undergo medical assessment and, if necessary, take a
      CBR driving test. In the case of all neurological disorders, the rules are
      stricter for professional drivers of cars and motorcycles as well as holders of
      driving licenses for heavy-goods vehicles and buses.

PMID- 14574778
TI  - [Multiple pregnancies: epidemiology and management].
AB  - Since the 1980s, the percentage of multiple pregnancies in the Netherlands has
      increased. Nowadays, the percentage of triplets is decreasing but there is still
      an increase in the percentage of twin pregnancies. A major cause is that Dutch
      women tend to delay starting a family until an advanced age. This increases their
      chances of a spontaneous multiple pregnancy. Moreover, they are prone to
      subfertility and consequently have a greater chance of undergoing treatments
      involving assisted-reproduction techniques such as intra-uterine insemination
      (IUI) and in-vitro fertilisation. In the Netherlands, the majority of higher
      order multiple pregnancies result from mild ovarian hyperstimulation in
      combination with IUI. In case of in-vitro fertilisation, since the practice of
      transferring a maximum of two embryos still results in 20-25% twin pregnancies,
      single-embryo transfer should be advocated more often.

PMID- 14574779
TI  - [Summary of the Dutch College of General Practitioners' practice guideline
      'Anemia'].
AB  - The Dutch College of General Practitioners' practice guideline concerning anaemia
      advises the general practitioner to carry out additional laboratory tests in
      patients with a decreased haemoglobin level (Hb) in order to establish the cause
      of the anaemia. In specified cases (premenopausal women with excessive vaginal
      bleeding and in some children with mild anaemia) these tests may initially be
      omitted. In these cases iron can be prescribed and, if a child has had an
      infectious disease within the previous month, to wait one month to see if levels
      return to normal. In older patients with iron-deficiency anaemia subsequent
      investigations should be performed in order to rule out gastro-intestinal
      neoplasm, even if the history and physical examination give no indication of
      this. In an anaemic patient at risk of thalassaemia trait, haemoglobin
      electrophoresis or chromatography should be performed if there is microcytosis
      and a serum ferritine level > 15 micrograms/l.

PMID- 14574780
TI  - [Diagnostic image (159). An elderly woman with shock and discoloration of an
      upper leg. Gas gangrene caused by C. septicum].
AB  - In an 80-year-old woman septic shock and gas gangrene were diagnosed secondary to
      a perforated carcinoma of the coecum.

PMID- 14574781
TI  - [A Turkish man with Behcet disease and recurrent acute abdomen].
AB  - Following a total hip prosthesis, a 52-year-old Turkish man with Behcet's disease
      developed persistent ileus due to intestinal perforations. Resection of the
      intestine was followed by new perforations, resulting in resection of another
      portion of the intestine and the start of immunosuppressive medication. Following
      the 5th resection for a perforated ulcer in the space of two weeks, an ileostomy
      was performed. One year later the stoma could be eliminated and the patient
      remained symptom-free. Behcet's disease is relatively rare in the Netherlands.
      However, the gastrointestinal complications may be life-threatening. Surgical
      intervention is then often necessary. Complications and recurrences are frequent.

PMID- 14574782
TI  - [The 2002/2003 influenza season in the Netherlands and the vaccine composition
      for the 2003/2004 season].
AB  - As in the 2000/2001 and 2001/2002 seasons, the influenza epidemic in the
      2002/2003 season started late (week 7 of 2003) and was only moderate in size.
      Influenza A (H3N2) and B viruses were detected in equal numbers among patients of
      general practitioners and these two viruses were therefore equally responsible
      for the epidemic. However, H3N2 viruses dominated isolates taken from hospitals.
      In haemagglutination-inhibition (HI) assays most of the H3N2 viruses proved
      highly reactive with antiserum to the vaccine-reference strain A/Moscow/10/99.
      This was also true for a number of isolates, including those obtained from
      nursing home residents, closely related to the reference strain A/Finland/170/03.
      However, an estimated 4% of the H3N2 isolates belonged to the variant
      A/Fujian/411/02 from China, which constituted the majority of the H3N2 viruses
      isolated in Europe in the later phase of the season. This variant reacted poorly
      with antiserum to A/Moscow/10/99. In H1 tests all influenza A(H1N1)-virus
      isolates and all B-virus isolates were closelyrelated to the corresponding
      vaccine-reference strains. Taking this data into consideration, the World Health
      Organization has advised the same vaccine composition for the 2003/2004 season as
      for the 2002/2003 season, namely: A/Moscow/10/99 (H3N2), A/New Caledonia/20/99
      (H1N1) and B/Hong Kong/330/01. There is the possibility of a mismatch occurring
      between the H3N2-vaccine strain and the circulating H3N2 viruses in the coming
      influenza season. In March and April 2003 there was an outbreak of influenza-A
      (H7N7) fowl plague in the Netherlands. A special monitoring survey revealed that
      91 people who had handled infected poultry became infected with the H7N7 virus.
      One of these later died as a result of this. None of the avian and human H7N7
      virus isolates examined contained human or porcine influenza-A virus genes.

PMID- 14574783
TI  - [Treatment of stroke by reducing the body temperature; 'Paracetamol
      (acetaminophen) in stroke' (PAIS): start of a clinical trial].
AB  - Subfebrile temperatures and fever in acute stroke are associated with poor
      functional outcome. A 1 degree C rise in body temperature may double the risk of
      a poor outcome in patients who are admitted within 12 hours from the onset of
      symptoms. Two randomised double-blind clinical trials in patients with acute
      ischaemic stroke have shown that treatment with a daily dose of 6 g paracetamol
      results in a small but rapid and potentially worthwhile reduction of 0.3 degree C
      (95% CI: 0.1-0.5) in body temperature. It has been hypothesized that early
      antipyretic therapy reduces the risk of death or dependency in patients with
      acute stroke, even if they are normothermic. For this reason, a multicentre,
      randomized, double-blind clinical trial comparing high-dose paracetamol with
      placebo in 2500 patients has been launched. This study has been named
      'Paracetamol (acetaminophen) in stroke' (PAIS). The primary outcome is death or
      dependency at three months. The study protocol is simple, and the amount of data
      to be gathered is limited. The trial will run for four years.

PMID- 14574784
TI  - [The clinical diagnosis 'wound botulism' in an injecting drug addict].

PMID- 14574785
TI  - [Stereotactic thick needle biopsy in diagnosis of non-palpable abnormality in the
      breast: a trustworthy alternative to excision biopsy].

PMID- 14574786
TI  - [Stereotactic thick needle biopsy in diagnosis of non-palpable abnormality in the
      breast: a trustworthy alternative to excision biopsy].

PMID- 14574787
TI  - [Stereotactic thick needle biopsy in diagnosis of non-palpable abnormality in the
      breast: a trustworthy alternative to excision biopsy].

PMID- 14574788
TI  - Pressure cooking: hospital boards under increased outside scrutiny.

PMID- 14574789
TI  - Latest hospital/insurer skirmish: who's holding the bag.

PMID- 14574790
TI  - Scrutiny's flip side: poor returns?

PMID- 14574791
TI  - Stopping the bleeding: study sees ERs as profit centers.

PMID- 14574792
TI  - Teacher preparation.

PMID- 14574793
TI  - Comparing deaf and hearing college students' mental arithmetic calculations under
      two interference conditions.
AB  - Deaf and hearing college students' mean reaction times (RTs) were compared on a
      mental calculation task in which they had to verify the accuracy of solutions to
      addition and multiplication problems. The deaf students were divided into higher
      and lower readers. Higher deaf readers and hearing students had similar RTs and
      accuracy on addition problems; their RTs were greater in the voicing interference
      mode than in the manual tapping interference mode. The lower deaf readers showed
      no RT differences between the two interference modes and had consistently lower
      RT performance and score accuracy across the verification tasks. On the
      verification task for multiplication problems, all participants showed a greater
      RT effect for manual tapping. The lower deaf readers were significantly less
      accurate on multiplication problems.

PMID- 14574794
TI  - Signs of resilience: assets that support deaf adults' success in bridging the
      deaf and hearing worlds.
AB  - A multiple-case exploratory study is used to describe intrapersonal, behavioral,
      and environmental assets that may build bridges for Deaf adults between the Deaf
      and hearing worlds. A study of three exemplary former community college students
      provides new information about internal resources that may empower Deaf
      individuals to achieve work and social success in interaction with environmental
      support, despite the vulnerabilities associated with their deafness. This study
      identifies 15 assets that may support resilience in Deaf adults, including
      authenticity and comfort with solitude. The authors hypothesize that social
      authenticity and comfort with solitude may be resilience-fostering intrapersonal
      assets of unique importance in the Deaf community. From the positive psychology
      perspective of recognizing and building on human strengths, the authors suggest
      that support of mutual asset-building with learning partners in the classroom is
      one way professors might promote optimal student achievement and life success for
      all students.

PMID- 14574795
TI  - Measuring students' metacognition in real-life situations.
AB  - Metacognitive performance of four groups of students (hearing high-achieving,
      hearing average-achieving, hearing under achieving, and deaf and hard of hearing)
      in first through third grade in the United Arab Emirates was examined and
      compared. Metacognition was measured using analyses of pictures depicting real
      life problematic events, situations, and behaviors. Participants drew on their
      ability to apply problem solving and logical reasoning through visual analysis
      and discrimination of test materials rather than through verbal analysis. Results
      revealed that metacognition is influenced by students' age. Older students scored
      significantly higher on the metacognitive measure than younger students. Further
      analysis indicated that hearing high-achieving students scored significantly
      higher on the test than the other three groups when the age variable was
      controlled for. Deaf and hard of hearing students performed similarly to age
      matched hearing students in applying reasoning skills to real-life situations.

PMID- 14574796
TI  - Self-assessments and other perceptions of successful adults who are deaf: an
      initial investigation.
AB  - More often than not, deafness is portrayed, not only in the literature in
      education and rehabilitation but in society in general, in a pathological way
      that focuses on deficiency, dysfunction, and deviance. Consequently, there has
      been a paucity of research on successful individuals who are deaf. The purpose of
      the present study was to help counter this tendency by gathering information from
      successful deaf adults. Fourteen deaf adults, who were nominated by their peers
      as being successful, participated in videotaped interviews. The interviews were
      transcribed, coded, and clustered according to common themes. Participants
      reflected on their success and made recommendations for children and youth who
      are deaf, parents, teachers, and employers. A summary of the results, limitations
      of the study, and recommendations for practice are provided.

PMID- 14574797
TI  - Using structured games to teach early fraction concepts to students who are deaf
      or hard of hearing.
AB  - The study focused on the development of the concept of fractions in a group of 11
      and 12-year-old students who were deaf or hard of hearing. The approach
      implemented in the study relied extensively on the use of games with very little
      formal instruction. It emphasized the development of appropriate language to
      facilitate an understanding of the notion of fractions through the investigation
      of concrete materials, pictorial representations, and interactions between
      students and teacher. The progress achieved by means of this approach is
      reported, and the implications of developing an understanding of fractions (and
      mathematics generally) among students who are deaf or hard of hearing are noted.

PMID- 14574798
TI  - Benefits of an Ed.D. program in deaf education: a survey.
AB  - Ten graduates and 3 ABD (all but dissertation) students in Lamar University's
      doctoral program in deaf studies/deaf education were surveyed about their
      perceptions of the benefits of earning a doctorate of education (Ed.D.) in their
      field. The program comprised course work on current content information on deaf
      education, an educational research component, a cognate area, and electives. As
      part of the program, researchers and scholars in areas related to deaf education
      were invited to campus to consult with doctoral students. Graduates found jobs at
      universities, community colleges, and departments of special education. Graduates
      ranked program components on the basis of perceived value; they rank-ordered the
      courses on the basis of their value to them in their current work. Graduates also
      commented on how the program enhanced their professional growth.

PMID- 14574799
TI  - An educational rationale for deaf students with multiple disabilities.
AB  - Deaf students with with multiple disabilities have a long history of limited
      opportunity, including limited access to educational opportunities available to
      their deaf peers. This article places the individual needs of deaf students with
      multiple disabilities in the context that guides much of deaf education--the
      importance of language acquisition. That emphasis provides a basis for placement
      and curriculum options for deaf students with multiple disabilities. The authors
      review the evolution of placement options, describe assumptions that should guide
      placement and curriculum decisions, and recommend practices for optimizing these
      students' education. Descriptions of three service delivery models-
      multidisciplinary, interdisciplinary, and transdisciplinary--are provided, as
      well as an overview of the effectiveness of person-centered planning for deaf
      students with multiple disabilities. Disability-specific resources are
      highlighted that relate to mental retardation, autism, visual impairments,
      learning disabilities, attention deficit hyperactivity disorder, emotional
      disorders, medical issues, and general resources.

PMID- 14574800
TI  - [Some controversial conditions in the management of chronic prostatitis/chronic
      pelvic pain syndrome].
AB  - Chronic prostatitis (CP)/chronic pelvic pain syndrome (CPPS) is a common problem
      of medically controversial condition that causes considerable morbidity and
      impact on life. Although there are many competing causes proposed, the etiology
      and pathogenesis of CP/CPPS remain unclear. The causative factors underlying the
      CPPS are not fully understood. The optimal management of CP/CPPS is still
      unknown. The guideline of diagnosis and management of CP/CPPS based on evidence
      base medicine is not yet established. Many problems are still not resolved, such
      as the significance of leukocytes and the role of inflammation in CP/CPPS, the
      significance of bacteria presence and the role of infection in CP/CPPS, the
      correlation between leukocytes/bacteria and severity of symptoms, how to divide
      the subgroups of CP/CPPS, the role of antimicrobial therapy in the treatment of
      men with CP/CPPS, why patients with category IIIb complain of symptoms, while
      those with category IV complain of none. Although CP/CPPS is now achieving
      greater recognition, well-designed studies with large sample size should be
      performed.

PMID- 14574801
TI  - [Transient compensatory hypertrophy and limited regeneration of the surgically
      removed rat ventral prostate].
AB  - OBJECTIVES: To confirm whether regeneration of prostate lobe indeed takes place
      on surgical lobectomy and if so, to what extent. Other issues studied are 1.
      whether the lobe regenerated is similar morphologically to that developing
      normally from neonatal origin to adulthood, and 2. the consequences of partial
      lobectomy on the contralateral lobe and the influence of sex steroid hormones on
      the regeneration process. METHODS: The effect of surgical removal of one of the
      ventral prostate lobes on the size of the contralateral lobe has been studied at
      various time intervals after lobectomy. RESULTS: The surgically extirpated
      ventral prostate lobe in rats regenerates attaining plateau size at 8-16 weeks
      post lobectomy. The regenerated lobe, however, remains significantly smaller than
      the original size. In early phase of post lobectomy (at 2 weeks) the
      contralateral lobe was significantly hypertrophied. It reverts to normal size on
      regeneration of the extirpated lobe with time. Orchiectomy carried out at the
      time of lobectomy caused a drastic reduction in the size of the remaining lobe,
      which was prevented by exogenous treatment with androgens. In animals receiving
      treatment with estrogens, the remaining lobe was partially but not fully
      atrophied. However, estrogens did not support the regeneration of the surgically
      removed lobe, which requires androgens. CONCLUSIONS: These studies demonstrate
      that surgical removal of one of the ventral prostate lobe leads to a process of
      regeneration. However, the regenerated lobe does not attain the normal size.

PMID- 14574803
TI  - [Allotransplantation of spermatogonial stem cells in KM mice].
AB  - OBJECTIVE: To study the feasibility of spermatogonial stem cell
      allotransplantation. METHODS: The spermatogonial stem cell allotransplantation
      was performed, without the use of immune inhibitor, in KM mice of similar gene
      types, and the spermatogenesis in recipients' testes was evaluated. The right
      testes were pierced for transplantation while the left ones were taken as
      control. RESULTS: Allotransplant germ cells in KM mice can recover normal
      function of spermatogenesis in the transplanted testis without any immune
      suppression. CONCLUSION: Allospermatogonial stem cells can be transplanted
      successfully among KM mice.

PMID- 14574802
TI  - [Vitamin D receptor gene Bsm I polymorphism and the susceptibility to prostate
      cancer in northern Chinese Han population].
AB  - OBJECTIVES: To investigate Bsm I single nucleotide polymorphism (SNP) of vitamin
      D receptor gene (VDRG) in low-risk Chinese Han population and its relationship to
      the susceptibility to prostate cancer (PCa), and to discuss the possible reason
      for the racial difference of PCa. METHODS: One hundred and three patients with
      PCa and 106 normal controls, mainly from Northern Chinese Han population, were
      enrolled in this study. Their blood samples were obtained, all of which were
      genotyped for Bsm I SNP by denaturing high performance liquid
      chromatography(DHPLC) methods using case-control study. RESULTS: The distribution
      of genotype and allele had no significant difference between PCa patients and
      normal controls (P > 0.05). The frequencies for the bb, Bb and BB genotypes in
      PCa patients and normal controls were 92.23%/94.34%, 7.77%/5.66%, and 0/0,
      respectively. The frequencies for B and b allele were 3.88%, 96.12% and 2.91%,
      97.09%, respectively. CONCLUSIONS: The results indicate no significant
      relationship between the VDRG polymorphisms and PCa in Northern Chinese Han
      population. The distribution of VDRG Bsm I SNP varies in different ethnic
      populations, which may be one reason for the racial difference of PCa.

PMID- 14574804
TI  - [Effects of mTR antisense oligodeoxynucleotide on telomerase activity and the
      expression of telomerase mTR in type A spermatogonia].
AB  - OBJECTIVES: To study the inhibitory effects of mouse telomerase RNA (mTR)
      antisense oligodeoxynucleotide(ASODN) on telomerase activity in rat
      spermatogonia. METHODS: 9-mer phosphorothioate mTR-ASODN was encapsulated by
      Lipofect AMINE 2000 (LF 2000) and transfected to type A spermatogonia in Snrague
      Dawley (SD) rat. Telomerase activity was detected by aid of TRAP-SYBR-Green
      staining and Bioluminescence technique in type A spermatogonia treated or
      untreated with ASODN. RESULTS: mTR-ASODN conjugated with LF 2000 could
      significantly inhibit telomerase activity of spermatogonia(P < 0.01). mTR mRNA
      level also decreased while the spermatogonia were treated with ASODN for 24 h. No
      change of telomerase activity and apoptosis were observed when SODN, RODN or
      single LF 2000 was used. CONCLUSIONS: Antisense oligodeoxynucleotide of mTR
      conjugated with LF 2000 could significantly inhibit telomerase activity of
      spermatogonia. mTR-ASODN might inhibit telomerase activity of spermatogonia at
      transcription level.

PMID- 14574805
TI  - [Establishment of prostatic hyperplasia model with castration beagle canines].
AB  - OBJECTIVE: To establish a prostatic hyperplasia model with Beagle canines.
      METHODS: Twenty-four two-year-old male Beagle canines were divided into treatment
      and control groups at random and were administrated testosterone propionate (TP)
      through intramuscular injection two months after castration. Three treatment
      groups were given 0.8, 2.5 and 7.5 mg/kg TP respectively, and the control was
      given the same volume of vehicle. Two months later, half of the animals were
      killed and the serum and prostate were prepared. After the wet weight and volume
      of prostate were measured, the dihydrotestosterone (DHT) level of serum and
      prostate were detected with DHT radioimmunoassay (RIA) kit, and paraffine section
      from canine prostate was stained by the HE methods. Pictures were taken by
      digital camera under microscope, and all the pictures were analyzed by computer
      for epithelial cell height and acinar luminal area of prostate with micro image
      analysis software. The canine prostate volume was measured with ultrasonic
      diagnosis instrument before castration, at two months after castration and at two
      months after being given TP. RESULTS: The ultrasonic results showed that the
      prostate volumes of all the canines were smaller at two months after castration
      than before castration (P < 0.05), and after having been administrated TP for two
      months, and the prostate volumes of all treatment groups were larger than those
      of the control group (P < 0.01). The wet weight of the prostate of the treatment
      group was higher than that of the control group (P < 0.05), and both had dose
      dependent relationship. The DHT level of serum and prostate of the canines became
      higher with the increase of TP dose. The results of micro image analysis showed
      that the acinar luminal area of prostate was enlarged, and the epithelial cell
      height increased with larger dose of TP. CONCLUSIONS: It is practicable to
      establish prostatic hyperplasia model in Beagle canines after two months of TP
      administration.

PMID- 14574806
TI  - [The change and implication of epididymis sialic acid following torsing/detorsing
      testes in rats].
AB  - OBJECTIVE: To investigate the change and implication of epididymis sialic acid
      after 24 hours following 2- or 4-hour torsing/detorsing of testes in rats.
      METHODS: Twenty-four adult male Sprague-Dawley rats were subjected to unilateral
      720 degrees testicular torsion for 2 and 4 hours and then repaired. The ischemic
      epididymides were collected for detecting the content of sialic acid by
      spectrophotometry. RESULTS: There was no statistically significant difference
      between the content of epididymis sialic acid after 24 hours following 2-hour
      torsing/detorsing of testes and that of the sham group, while significant
      difference was found between the content of epididymis sialic acid after 24 hours
      following 4-hours torsing/detorsing of testes and that of sham group.
      CONCLUSIONS: Sialic acidsecreting-function of epididymis can remain normal after
      one day following 2-hour torsing/detorsing of testes, and be injured after one
      day following 4-hour torsing/detorsing of testes. The epididymis remains
      resistant to ischemic damage during testicular ischemia.

PMID- 14574807
TI  - [Diagnostic value of complexed prostate-specific antigen for prostate cancer].
AB  - OBJECTIVE: To assess the clinical value of serum complexed prostate-specific
      antigen(cPSA) in the diagnosis of prostate cancer (PCa). METHODS: Serum samples
      were obtained from 110 men with untreated benign prostatic hyperplasia (BPH) and
      78 men with untreated PCa. The levels of cPSA, total PSA (tPSA) were determined
      by autoimmunochemistry luminescence method. RESULTS: Both cPSA and cPSA/tPSA
      ratio were significantly different between patients with PCa and BPH (P < 0.005),
      especially, in men with tPSA values between 4.0-10.0 micrograms/L (the diagnostic
      gray zone). When cPSA/tPSA > or = 0.78 was taken as the cut-off value conjugated
      with tPSA < or = 10.0 micrograms/L, the sensitivity, specificity, negative
      predictive value and positive predictive value were as high as 97.8%, 95.8%,
      81.9% and 96.5%. CONCLUSIONS: With the introduction of cPSA and cPSA/tPSA ratio,
      early diagnosis of PCa by the assessment of tPSA has been made more sensitive and
      reliable, especially when the tPSA is within the diagnostic gray zone.

PMID- 14574808
TI  - [Maximal androgen blockade and maximal androgen blockade combined with 125I
      brachytherapy for prostatic cancer].
AB  - OBJECTIVE: To assess the effect of the maximal androgen blockade(MAB) and MAB
      combined with 125I brachytherapy on prostatic cancer. METHODS: Forty-four
      patients with prostatic cancer (from 1993 to 2002), 28 at pathologic stage C and
      16 at stage D, were analyzed retrospectively. Thirty-five of them were treated by
      bilateral orchidectomy and anti-androgen drugs, i.e. MAB, and 9 treated by MAB
      combined with 125I brachytherapy. The survival rates and the variation of serum
      prostate-specific antigen (PSA) levels between pre- and post-treatment were
      compared. RESULTS: The level of PSA decreased from 60.3 micrograms/L to 12.1
      micrograms/L in 35 patients treated by MAB, and from 72.1 micrograms/L to 3.6
      micrograms/L in 9 patients treated by MAB combined with 125I brachytherapy after
      6 months. The post-treatment survival rates were 81.3% (26/32, excluding 3 deaths
      by other diseases) for patients treated by MAB after a mean follow-up of 39.2 (9
      84) months and 100% for patients by MAB combined with 125I brachytherapy after a
      mean follow-up of 13(7-24) months. CONCLUSION: MAB and MAB combined with 125I
      brachytherapy are effective for patients with prostatic cancer.

PMID- 14574809
TI  - [Real-time fluorescent PCR for screening AZFc/DAZ microdeletions on the Y
      chromosome in male infertility patients].
AB  - OBJECTIVE: To develop a real-time fluorescent PCR protocol suitable for the
      routine screening of AZFc/DAZ microdeletions on the Y chromosome in azoospermic
      and oligozoospermic male infertility patients. METHODS: A set of real-time
      fluorescent PCR was established. Eighty-seven azoospermic and ligozoospermic
      patients undergoing ICSI in the IVF center and 30 azoospermic men undergoing
      testicular biopsy in the clinic of urology surgery were screened for AZFc/DAZ
      microdeletions of Y chromosome. RESULTS: Eleven cases (9.4%) of AZFc/DAZ
      microdeletions were found in 117 cases of azoospermic and oligozoospermic
      patients by screening of realtime fluorescent PCR. Four cases (6.6%) were found
      in 61 oligozoospermic patients, and 7 cases (12.5%) were found in 56 azoospermic
      patients. CONCLUSION: The real-time fluorescent PCR protocol presented in this
      study is an easy and reliable method for detection of AZFc/DAZ microdeletions on
      the Y chromosome, which yields identical results to those of the multiplex PCR.

PMID- 14574810
TI  - [Analysis of the changes of movement function and viability in human spermatozoa
      induced by reactive oxygen species].
AB  - OBJECTIVES: To analyze the changes of movement function and viability in human
      spermatozoa induced by reactive oxygen species(ROS), and to prove whether ROS
      were one of the causes of the movement dysfunction of spermatozoa. METHODS:
      Spermatozoa with normal physiological functions selected from semen samples by
      Percoll gradient centrifugation technique were regarded as normal sperm models.
      ROS were generated by hypoxanthine-xanthine oxidase system and then incubated
      with normal sperm models under aerobic environment. After model spermatozoa were
      incubated with ROS, movement parameters of spermatozoa were analyzed by computer
      assisted semen analysis (CASA) system. RESULTS: Compared with the control group,
      after model spermatozoa were incubated with ROS for 30 minutes, motility,
      curvilinear velocity(VCL), straight line velocity (VSL) and average path velocity
      (VAP) of the spermatozoa were significantly decreased (P < 0.001), but amplitude
      of lateral head displacement (ALH) was insignificant (P > 0.05). When incubated
      with ROS for 60 minutes, spermatozoa almost lost movement function and all
      movement parameters of spermatozoa inclined to zero. CONCLUSIONS: When normal
      spermatozoa were incubated with ROS, movement functions of sperm were decreased.
      It was demonstrated that ROS were one of the causes of the movement dysfunction
      of spermatozoa.

PMID- 14574811
TI  - [Effects of hyperbaric oxygenation on rabbits 'testes with varicocele].
AB  - OBJECTIVE: To study the mechanism of male infertility caused by varicocele by
      evaluating the effects of hyperbaric oxygenation (HBO) therapy on the testicular
      tissue morphology and function of rabbit model with varicocele(VC). METHODS:
      Twenty-four mature male rabbits were randomly divided into three groups: pseudo
      operation, VC model and VC model administered by HBO. Experimental varicocele was
      induced by partial ligation of the left "lumbotesticular" trunk vein in rabbits.
      HBO was administered to one of the two groups of VC model rabbits after the
      operation. Weight and volume of both testes, parameters of seminal fluid,
      histological changes of testicular tissues, MTDs, TFI, and Sertoli cell index
      (SI) of seminiferous tubules were studied. RESULTS: The average weight and volume
      of the left testes significantly increased in the rabbits treated by HBO. The
      semen quality was improved, and MTDs increased significantly compared with VC
      group(P < 0.0001). The testicular tissue morphology became nearly normal in VC +
      HBO group. CONCLUSIONS: 1. Both the structure and spermatogenetic function of
      testes can be damaged by the presence of varicocele; 2. Chronic ischemia, anoxia
      and microcircular dysfunction may be the key process and essential factor that
      make varicocele contributive to testicular damage and spermatogenetic
      dysfunction; 3. HBO can effectively alleviate, even eliminate, chronic ischemia,
      anoxia and microcircular dysfunction in testicular tissues with varicocele, and
      thus protect the structure and functions of testes.

PMID- 14574812
TI  - [Inhibin B levels of serum and seminal plasma in fertile and infertile males].
AB  - OBJECTIVES: To investigate the possible differences in the inhibin B levels of
      seminal plasma and serum between fertile and infertile males and to obtain
      information on the relation between serum inhibin B or seminal plasma inhibin B
      and spermatogenesis. METHODS: Semen and blood samples were collected from
      fertile(n = 20), oligospermia(n = 20), asthenospermia(n = 22) and non-obstructive
      azoospermia(NOA) (n = 20) males at 8:00 am = 10:00 am. Semen parameters were
      analyzed. Levels of inhibin B in seminal plasma and serum, ACP, Fru, alpha-Glu in
      seminal plasma, serum levels of FSH, T, LH were determined. RESULTS: Both levels
      of serum inhibin B and levels of seminal plasma inhibin B correlated
      significantly negatively with serum FSH(r = -0.536, P < 0.001 vs r = -0.288, P =
      0.01), and statistically positively with sperm concentration(r = 0.49, P < 0.001
      vs r = 0.48, P < 0.001). There was positive correlation between levels of seminal
      plasma inhibin B and activity of alpha-Glu in seminal plasma (r = 0.377, P =
      0.001). The difference in levels of seminal plasma inhibin B was found only
      between fertile males or asthenospermia and NOA (P < 0.01 and P < 0.05,
      respectively). However, significant differences in levels of serum inhibin B were
      found not only between males with normal sperm concentration (including fertile
      males and asthenospermia) and NOA (P < 0.01), fertile males and oligospermia (P <
      0.05), but also between oligospermia and NOA (P < 0.05). There was no correlation
      between serum inhibin B and seminal plasma inhibin B. CONCLUSIONS: Both levels of
      serum inhibin B and seminal plasma inhibin B could reflect testis spermatogenesis
      status. Levels of seminal plasma inhibin B could also reflect the function of
      seminiferous duct, but the wide range of values limited its applicability.

PMID- 14574813
TI  - [Survey of the prevalence of chronic prostatitis in men with premature
      ejaculation].
AB  - OBJECTIVE: To investigate the prevalence of chronic prostatitis in men with
      premature ejaculation. METHODS: The segmented urine specimens before and after
      prostatic massage and the expressed prostatic secretion specimens from 106
      patients with premature ejaculation and 38 controls were evaluated by microscopic
      and/or bacteriological studies. The prevalence of premature ejaculation was also
      investigated in 120 patients with chronic prostatitis. RESULTS: Prostatic
      inflammation was found in 46.2% and chronic bacterial prostatitis in 34.7% of the
      subjects with premature ejaculation, respectively. Compared with the controls,
      the findings were statistically significant (P < 0.05). The prevalence of
      premature ejaculation in the patients with chronic prostatitis was 47.5%
      (57/120). CONCLUSIONS: Chronic prostatic inflammation may play a role in the
      pathogenesis of some cases of premature ejaculation and it is important to give a
      careful examination of the prostate before initiating any therapy for premature
      ejaculation.

PMID- 14574814
TI  - [Sexual dysfunction in patients with chronic renal failure].
AB  - Sexual dysfunction is a highly prevalent problem among patients with chronic
      renal failure, which affects patients in the quality of life. However, it has not
      received enough attention. The genesis of sexual dysfunction is multifactorial,
      including physiological, psychological and organic factors. This review
      summarized the incidence, main manifestation, evaluation, risk factors and
      treatments associated with sexual dysfunction in patient of the chronic renal
      failure.

PMID- 14574815
TI  - [New progress on diagnosis and treatment of female sexual dysfunction].
AB  - Female sexual dysfunction(FSD) is an age-related progressive disease and may
      affect up to half of adult women. It has not been paid attention to for a long
      time. This paper reviews the current information on the anatomy, physiology and
      pathophysiology of FSD. In addition the diagnosis and treatment of FSD are also
      described. It aims at improving the knowledge of FSD.

PMID- 14574816
TI  - [Genetic variations and possible therapeutic ways of male infertility].
AB  - Chromosome aberrant and some gene mutations play an important role in male
      infertility. A knowledge of a variety of new genetic causes is crucial for the
      prevention and treatment of male infertility. This review focused on known
      genetic causes of male infertility, male fertility-related candidate genes from
      knockout mice, genetic analysis and treatment of infertility in men.

PMID- 14574817
TI  - [Advances in the studies of Chlamydia trachomatis infection in males].
AB  - Chlamydia trachomatis(Ct) infection in reproductive tract is one of the most
      common sexually transmitted diseases at present. However, relatively fewer
      studies are made on Ct infection in men. The paper reviews the epidemiology of Ct
      infection in males, Ct infection and male diseases, Ct infection and male
      infertility, and the detection of Ct infection in men. It aims at providing a
      theoretical basis and a practical guide for the prevention and control of Ct
      infection in men.

PMID- 14574818
TI  - [Effects of shouwu-huanjing recipe on human sperm motility and fertility in
      vitro].
AB  - OBJECTIVE: To observe the effect of Shouwu-Huanjing Recipe(SWHJR) medicated serum
      on human sperm motility and fertility in vitro. METHODS: Human sperm was co
      cultured with SWHJR medicated serum in vitro. Human sperm motility was evaluated
      by computer-assisted semen analysis(CASA). The acrosome reaction and the
      capability of penetrating zona-free hamster eggs were also observed. RESULTS: The
      co-cultured SWHJR medicated serum significantly increased the sperm motion
      velocity(VAP, VCL, VSL) (P < 0.01), the amplitude of lateral head movement (ALH)
      and the beat frequency of flagellum(BCF), the density of progressive motility
      sperms (P < 0.05), the acrosome reaction rate(P < 0.001), the fertilization
      rate(FR) and the fertilization index (FI) in sperm penetration assay(SPA) test (P
      < 0.01). The stimulation of SWHJR medicated serum occurred in dose-dependent
      manner. CONCLUSION: SWHJR can improve human sperm motility and fertility.

PMID- 14574819
TI  - OR managers report high job satisfaction despite pressure.

PMID- 14574820
TI  - Jury awards fired OR director $4 million.

PMID- 14574821
TI  - Big growth forecast for surgery by 2020.

PMID- 14574822
TI  - Self-scheduling an aid to staff retention.

PMID- 14574823
TI  - More ASC managers receive salary hike.

PMID- 14574824
TI  - Building an ASC team from the ground up.

PMID- 14574825
TI  - Modern views of autism.

PMID- 14574826
TI  - Autism spectrum disorders: early detection, intervention, education, and
      psychopharmacological management.
AB  - Our understanding and treatment of children with autism have changed dramatically
      since Leo Kanner first formally documented the disorder in 1943. With reference
      to the historical context, this paper reviews recent research addressing 4 major
      issues: early detection, intervention, education, and psychopharmacological
      management of children with autism and related (autistic) spectrum disorders
      (hereafter, "autism"). We conclude from our review of the evidence that, in the
      absence of additional, more compelling data, the clinical usefulness of existing
      screening instruments remains questionable. However, the potential importance of
      such research is underscored by the clear benefits of early behavioural
      intervention: despite differences in orientation, outcomes for children with
      autism can be significantly enhanced with early intensive intervention. Although
      many questions remain (notably, What are the critical therapeutic components? For
      whom? For what domains of development? For what level of intensity and
      duration?), interventions shown to be effective are all carefully planned,
      engineered, monitored, and designed to target specific skill domains. Including
      children with autism in regular classes within the public school system poses
      several challenges, the most pressing of which is the large number of school
      personnel who need to be trained in evidence-based teaching and behavioural
      management practices. Finally, psychotropic drugs may help to reduce some
      symptoms, but they are neither curative nor a substitute for other forms of
      support and intervention.

PMID- 14574827
TI  - Diagnosis and epidemiology of autism spectrum disorders.
AB  - In this paper, we give an overview of the diagnostic categories of autism and
      other pervasive developmental disorders (PDDs) and discuss the changes in the DSM
      classification system over the past 20 years. We describe each subtype of PDD,
      along with comorbid psychiatric conditions, assessment guidelines, and tools for
      diagnosis. The epidemiology of autism has generated much discussion and research;
      we report the most recent data, as well as recent findings about controversial
      issues purporting to cause the increased prevalence rate observed in the past
      decade. Finally, we discuss the prognosis for individuals with autism, indicating
      the challenges faced by patients, families, and professionals aiming to optimize
      their outcome.

PMID- 14574828
TI  - Genetic and neurodevelopmental influences in autistic disorder.
AB  - OBJECTIVE: In the past, autism was considered to be largely psychogenic. However,
      research in the last 2 decades indicates that autism is largely caused by genetic
      factors that lead to abnormal brain development. This article reviews research
      into the genetic and neurodevelopmental factors underlying autism. METHODS: We
      review the findings from genetic and brain-imaging studies of autism over the
      past 15 years and synthesize these findings as a guide for future research.
      RESULTS: Genome scans and association studies have suggested potential genomic
      regions and genes, respectively, that may be involved in the etiology of autism,
      and there have been some replications of these results. Similarly, the findings
      that brain volume is exaggerated in autism and corpus callosum size is reduced
      have also been independently replicated. Unfortunately, studies of other
      subcortical structures remain inconclusive or contradictory. CONCLUSIONS:
      Overwhelming evidence now supports a neurobiological basis for autism. However,
      further refinements will be needed to guide future studies, particularly to
      identify the most informative phenotypes to investigate. Additionally, studies
      examining the role of genetic factors in the brain abnormalities underlying
      autism will likely lead to further findings that will enhance our understanding
      of autism's causes.

PMID- 14574829
TI  - Attitudes of senior psychiatry residents toward persons with intellectual
      disabilities.
AB  - OBJECTIVES: This study examined the attitudes of senior residents in psychiatry
      toward persons with intellectual disabilities. Examining residents' attitudes
      will highlight areas of training that could be enhanced to better prepare
      psychiatrists to work with individuals with intellectual disabilities. METHOD: A
      questionnaire was distributed to senior psychiatry residents at a Canada-wide
      preparatory session for the Royal College of Physicians and Surgeons of Canada.
      Included in the questionnaire was the Community Living Attitudes Scale Mental
      Retardation--Short Form (CLAS) as well as demographic items (for example, age,
      sex, and marital status) and questions about training in intellectual
      disabilities. Scores on the 4 CLAS subscales (Empowerment, Similarity, Exclusion,
      and Sheltering) are reported, and analyses of variance were performed to identify
      factors associated with each subscale score. The residents' scores are compared
      with those obtained in surveys of other groups. RESULTS: Fifty-eight senior
      residents from across Canada completed the questionnaire. The residents' scores
      favored Empowerment and Similarity over Exclusion and Sheltering. Men and women
      responded differently. Training in intellectual disabilities during residency
      only appeared to influence the Similarity subscale scores. CONCLUSION: Senior
      psychiatry residents hold attitudes toward persons with intellectual disabilities
      that are not entirely consistent with the community living philosophic paradigm.
      More research is needed to uncover how attitudes of psychiatrists develop, as
      well as how training can influence attitudes.

PMID- 14574830
TI  - The efficacy of 2 different dosages of methylphenidate in treating adults with
      attention-deficit hyperactivity disorder.
AB  - OBJECTIVE: To evaluate the efficacy of methylphenidate in treating adults with
      attention-deficit hyperactivity disorder (ADHD), using subjective (self-report)
      and objective (computerized test) measures. METHOD: This double-blind crossover
      trial of placebo vs methylphenidate included subjects with childhood and current
      ADHD symptoms, IQs above 80, no other psychiatric condition explaining their
      difficulties or requiring other treatment, and no substance abuse in the previous
      6 months. We administered 10 mg 3 times daily of medication (that is, placebo or
      methylphenidate) for 2 weeks. On the final day, subjects completed self-report
      measures and were tested on computerized tests. We then increased dosage to 15 mg
      3 times daily for 2 weeks and administered a complete reassessment on the final
      day. Following a 1-week washout, we repeated this process on the second
      medication (that is, placebo or methylphenidate). RESULTS: Thirty adults with
      ADHD participated. Self-report measures and computerized tests showed significant
      improvements in ADHD symptoms on methylphenidate, compared with placebo. Other
      psychiatric symptoms (notably, anxiety and depression) were alleviated with
      methylphenidate. There was no significant difference between the 2 dosages of
      methylphenidate. CONCLUSION: Methylphenidate is effective in improving ADHD
      symptoms in adults with ADHD, is well tolerated, and has minimal side effects.

PMID- 14574831
TI  - Delirium in hospital: an underreported event at discharge.
AB  - OBJECTIVE: Delirium, an important event in hospital, is associated with
      significant mortality and morbidity. Most patients with delirium recover fully;
      however, when left untreated, delirium may progress to stupor, coma, or death.
      Delirium is less likely to resolve completely in elderly patients in whom
      persistent cognitive deficits commonly occur. The extent to which this
      information is available to family doctors after discharge was investigated.
      METHOD: A total of 31 patients with delirium who were referred to consultation
      liaison psychiatry were assessed using standardized measures. Medical services
      completed discharge summaries on these patients; a chart review captured the
      extent to which the diagnosis of delirium and the involvement of psychiatry was
      recorded in the discharge summaries. RESULTS: In structured discharge summaries,
      a reference to delirium occurrence was found in 55% of cases. In unstructured
      discharge summaries, the reporting was much lower (16% of cases). Delirium was
      more likely to be reported in women than in men, when it was more severe, or when
      it was the principal reason for admission, rather than when it occurred during an
      admission for some other reason. CONCLUSIONS: Delirium episodes that occur during
      a period of hospitalization for treatment of any medical disorder are
      underreported, even when specifically diagnosed. Structured discharge summaries
      tend to increase the rate of reporting.

PMID- 14574832
TI  - Removing barriers to treatment of first-episode psychotic disorders.
AB  - OBJECTIVE: To describe changes aimed at removing barriers to appropriate and
      timely assessment and treatment of first-episode psychosis (FEP) and to present
      descriptive data regarding the potential impact of such changes on treated
      incidence, referral patterns, and treatment delay. METHOD: We collected
      demographic and clinical information, including duration of untreated psychosis
      (DUP), on 196 persons referred for an initial assessment over a 3-year period.
      RESULTS: The number of identified FEP cases increased and DUP decreased over the
      3-year period. The data suggest a differentially greater reduction in DUP in
      cases referred from sources other than health care. CONCLUSION: These preliminary
      results suggest that, when setting up programs for FEP, relatively simple changes
      designed to improve access may improve treated incidence and reduce treatment
      delays.

PMID- 14574833
TI  - Response of catatonic schizophrenia to amisulpride: a case report.

PMID- 14574834
TI  - Medication noncompliance among psychiatric outpatients in Iran.

PMID- 14574835
TI  - Diogenes syndrome in a pair of siblings.

PMID- 14574836
TI  - Treatment option for seasonal affective disorder.

PMID- 14574837
TI  - Factitious anemia and magnetic resonance imaging abnormalities.

PMID- 14574838
TI  - Pregnancy and respiratory nocturnal panic attacks.

PMID- 14574839
TI  - [Current topics on classification and nomenclature of bacteria classification of
      Mycobacterium tuberculosis complex on the basis of its genomic structures].

PMID- 14574840
TI  - [Detection of MRSA with antimicrobial susceptibility by using chemiluminescent
      assay].
AB  - Chemiluminescent assay can give the result of the detection of MRSA about 13
      hours more rapidly than conventional broth microdilution method. In order to
      apply chemiluminescent assay to detection of MRSA, we compared MIC and
      antimicrobial susceptibility to MPIPC in using chemiluminescent assay with these
      in using broth microdilution method. In MSSA, rate of concordance of MIC and
      antimicrobial susceptibility to MPIPC obtained by both methods was 87%, but all
      MICs come to be agreed by modifying the concentration of bacterial liquid. In
      MRSA, all MICs and susceptibility to MPIPC are agreed in both methods. Although
      we have used chemiluminescent assay to detect MRSA for one year, no trouble has
      been reported by clinical side. The chemiluminescent assay is evaluated to be
      good in detecting MRSA.

PMID- 14574841
TI  - [Epidemiological investigation of MRSA with antagonistic effects of beta-lactam
      antibiotic and vancomycin].
AB  - The combination of vancomycin and beta-lactam antibiotic synergistically is known
      to act on vancomycin-susceptible Staphylococcus aureus (VSSA). But some MRSA with
      the antagonism in the combination of vancomycin and beta-lactam antibiotic was
      identified in Japan. We called the MRSA "beta-lactam antibiotic-induced
      vancomycin-resistant MRSA (BIVR)", to distinguish it from hetero-VISA. The
      percentage of hetero-VISA isolated in Japan that Hiramatsu et al. reported in The
      Lancet in 1997 was that of "candidate-hetero-VISA" because it did not satisfy the
      criteria for detection of hetero-VISA that they proposed. Therefore, except for
      Mu3, a strictly defined hetero-VISA strain has never been detected in Japan.
      However, BIVR is certainly detectable in Japan. We performed a retrospective
      study of BIVR in 189 MRSA strains isolated from blood between 1978 and 1999 at
      the same institution. To performed a retrospective study, 189 MRSA strains were
      divided such as 1978-1984 (45strains), 1985-1989 (45strains), 1990-1994
      (49strains), 1995-1999 (50strains). MIC90 of anti-MRSA drugs according to above
      chronological transition were 2, 2, 2, 1 as vancomycin, 2, 1, 1, 1 as
      teicoplanin, and 8, 8, 1, 1 microgram/mL as arbekacin, respectively, and then the
      detection rate of BIVR was 2.2, 2.2, 6.1, 10.4%, respectively. The BIVR detection
      rate in MRSA isolated from blood at 14 institutions was 14.8% (12/81) in 1999
      2002, and that of non-blood was 4.6% (42/905) (p < 0.001; chi 2-t examination).
      Of particular importance is that the percentage of BIVR isolated from blood is
      higher than that from non-blood, and the detection rate of BIVR from blood
      increases annually.

PMID- 14574842
TI  - [Survey of the past history of measles and rubella and advocacy for vaccination
      and certificates of vaccination at entry to kindergarten, primary school and
      junior high school in Kurashiki City--to improve the vaccination rate].
AB  - Although there have been measles outbreaks involving more than 100,000 patients
      every few years in Japan, vaccination is not compulsory under Japanese law and
      the vaccination rate remains low. In addition, because MMR vaccines have been
      suspended due to complications, monovalent measles vaccine is still used and
      administered only once for life. Under these circumstances, a new system was
      started to develop motivation for vaccination in order to try to eliminate
      measles and rubella. Although educational campaigns for vaccination are
      important, their effect is frequently temporary. To maintain a high vaccination
      rate after such campaigns, we advocated checking children for susceptibility,
      recommended vaccination and asked for certificates of vaccination at school
      entry. The participating subjects were 65/68 kindergartens, 55/55 primary schools
      and 24/24 junior high schools in Kurashiki City, Japan. The total number of
      subjects was 11,365. The susceptibility rate for measles and the unknown rate
      were 5.6% and 2.0% at kindergartens, 4.6% and 4.4% at primary schools, and 3.0%
      and 8.3% at junior high schools, whereas the susceptibility rate for rubella and
      the unknown rate were 14.0% and 2.3% at kindergartens, 21.8% and 5.4% at primary
      schools, and 35.2% and 11.7% at junior high schools. Among the children who were
      susceptible to measles, we confirmed that a certificate of vaccination was
      presented by 38.0% of pupils in kindergartens, 85.3% of those in primary schools
      and 43.7% of those in junior high schools. As for rubella, we confirmed 21.8%
      presented a certificate in kindergartens, 28.6% in primary schools and 11.6% in
      junior high schools. As a result, we achieved our goal for measles, which was
      previously determined as more than 90% for students with past history of
      infection or vaccination. However, we could not attain our goal for rubella.
      These systems were more effective than educational campaigns alone and were
      thought to increase the motivation for vaccination through their continuation.
      The rate of those who could not receive the vaccination due to allergy or seizure
      among the susceptible was 26% in total but more than 40% in some schools. We
      should educate not only parents but also doctors regarding vaccination and
      advocate that it be done.

PMID- 14574843
TI  - [Clinical analysis of aseptic meningitis caused by echovirus 13].
AB  - We examined the clinical symptoms and laboratory findings of 21 children with
      aseptic meningitis caused by echovirus 13 during the summer of 2002. All patients
      (mean age: 8.3 years) complained of fever and headache. Some had mild vomiting
      and some had severe vomiting of 4 times or more. In the early stage of the
      disease, the mean count of WBC was 8,283/microliter, mean level of CRP was 0.8
      mg/dl, and there were no abnormalities in levels of GOT, GPT, or LDH. The levels
      of protein and sugar, in cerebrospinal fluid showed no abnormalities, and mean
      total cell count was 560/microliter. The mean number of polynuclear cells was
      357/microliter, and of mononuclear cells was 203/microliter, showing polynuclear
      cell predominance. In the recovery period, the tendency to polynuclear cell
      predominance in the early stage of the disease shifted to mononuclear
      predominance. One of the 21 patients exhibited multinucleated cell predominance
      in the cerebrospinal fluid, a high CRP value of 6.2 mg/dl, as well as symptoms of
      restlessness including numbness of the limbs, hyperpnea, and excitation, needed
      careful diagnosis as aseptic meningitis. Almost all of the patients were mild
      cases, and no large differences were seen with the clinical and laboratory
      findings in previous reports of echovirus aseptic meningitis.

PMID- 14574844
TI  - [A case of severe eosinophilia in the acute phase of Opisthorchis viverrini
      infection].
AB  - A 26-year-old woman Japanese public official servant in Lao People's Democratic
      Republic was introduced to our hospital on December 12, 2002, because of two
      months duration of low grade fever and severe eosinophilia. There was no
      significant finding in physical examination. Laboratory tests showed leukocytosis
      (15,700/microliter) with severe eosinophilia (42%), and no abnormal lymphocyte
      was observed. Furthermore, elevation in alkaline phosphatase (748 IU/l), gamma
      glutamyl transpeptidase (190 IU/l), leucine aminopeptidase (150 IU/l), and slight
      elevation in CRP (2.8 mg/dl) were pointed out. A computed tomographic scan of the
      abdomen obtained multiple cystic lesions in the right lobe of the liver. On
      parasitological study, a stool specimen examined by the formalin-ether
      concentration method revealed positive for Opisthorchis viverrini eggs. She was
      orally administered with 40 mg/kg of praziquantel a day for two consecutive days.
      Following check-up by medical-affairs official at Embassy of Japan in Lao PDR
      confirmed the normal eosinophil count and her fever disappeared. It was
      considered eosinophilia in this case was induced by acute phase of severe
      ophisthorchiasis.

PMID- 14574845
TI  - [A case of Legionnaires' disease with acute renal failure improved by continuous
      hemodiafiltration].
AB  - A 52-year-old man was admitted to our hospital because of fever and dyspnea.
      Chest X-ray film showed infiltrative shadows in the right lower lung fields and
      serum creatinine was 6.7 mg/dl. The patient was diagnosed as pneumonia
      complicated with acute renal failure. He was treated with antimicrobial therapy.
      However he developed respiratory failure and exhibited mental confusion.
      Legionnaires' disease was suspected, because pneumonia was found to be associated
      with multiple organ dysfunction. We started treatment with intravenous
      administration of minocycline and continuous hemodiafiltration and his condition
      had been rapidly improved. We diagnosed this case as legionnaires' disease due to
      the positive of urinary Legionella pneumophila serogroup 1 antigen. Since the
      cases of legionnaires' disease with acute renal failure are serious, prompt
      diagnosis and adequate treatment are essential.

PMID- 14574846
TI  - [The detection of bacteria using in vitro whole blood models--the
      characterization of microscopy, Hybrisep and polymerase chain reaction].

PMID- 14574847
TI  - [Incidence of Q fever pneumonia in community-acquired pneumonia around Okayama
      City--the second report].

PMID- 14574848
TI  - [Progress in the diagnosis of colorectal cancer].

PMID- 14574849
TI  - [Epidemiology of colorectal cancer among Japanese].

PMID- 14574850
TI  - [Descriptive epidemiology of colorectal cancer--international comparison].

PMID- 14574851
TI  - [Risk factors in colorectal cancer].

PMID- 14574852
TI  - [Lifestyle and colorectal cancer].

PMID- 14574853
TI  - [Polymorphism in colorectal cancer].

PMID- 14574854
TI  - [Cancer susceptibility and familial predisposition in colorectal cancer].

PMID- 14574856
TI  - [Molecular mechanisms involved in colon carcinogenesis].

PMID- 14574855
TI  - [Mechanism of carcinogenesis in colorectal cancer].

PMID- 14574857
TI  - [Mechanism of carcinogenesis in colorectal cancer: Precancerous lesions].

PMID- 14574858
TI  - [Genetics of colon carcinogenesis].

PMID- 14574859
TI  - [Genetic changes in colorectal cancer].

PMID- 14574860
TI  - [Molecular biology of colorectal cancer--Genetic abnormality: an aspect for an
      MSI pathway].

PMID- 14574861
TI  - [Molecular biology of colorectal cancer: Growth factor and signaling pathways].

PMID- 14574862
TI  - [Molecular biology of colorectal cancer: The cell cycle and its regulation].

PMID- 14574864
TI  - [Metastasis-associated genes in colorectal cancer].

PMID- 14574863
TI  - [Angiogenesis and metastasis in colorectal cancer].

PMID- 14574865
TI  - [Invasiveness and metastasis in colorectal cancer: P53 gene alteration associated
      with hepatic metastasis].

PMID- 14574866
TI  - [Role of CD44 and MT1-MMP in colorectal cancer invasion and metastasis].

PMID- 14574867
TI  - [K-ras mutation and liver micrometastasis in colorectal cancer].

PMID- 14574868
TI  - [Macroscopic and histological classification of large bowel cancer].

PMID- 14574869
TI  - [Pathological diagnosis and problems in colorectal cancer].

PMID- 14574870
TI  - [Management of treatment in nodule-aggregating colorectal cancer].

PMID- 14574871
TI  - [Endoscopic and radiological diagnosis of early colorectal cancer].

PMID- 14574872
TI  - [Diagnosis of early colorectal cancer by magnifying colonoscopy].

PMID- 14574873
TI  - [Endoscopic diagnosis of early colorectal cancer].

PMID- 14574874
TI  - [Clinical application and usefulness of MDCT colonography in diagnosis of
      colorectal neoplasms, including early colorectal cancer].

PMID- 14574875
TI  - [Diagnosis of colorectal cancer with FDG-PET].

PMID- 14574876
TI  - [Barium enema examination in diagnosis of colorectal cancer].

PMID- 14574877
TI  - [Endoscopic ultrasonography for diagnosis of colorectal cancer].

PMID- 14574878
TI  - [Diagnosis of advanced colorectal cancer].

PMID- 14574879
TI  - [Hereditary nonpolyposis colorectal cancer].

PMID- 14574880
TI  - [Tumor marker and its clinical significance in diagnosis of colorectal cancer].

PMID- 14574881
TI  - [Molecular detection of tumor DNA in the serum of colorectal cancer patients].

PMID- 14574882
TI  - [Faecal occult blood test and mass screening for colorectal cancer].

PMID- 14574883
TI  - [Function of MMP-7 in colorectal cancer].

PMID- 14574884
TI  - [Significance of RhoC expression in terms of invasion and metastasis of
      colorectal cancer].

PMID- 14574885
TI  - [Expression of trypsin and cancer proliferation in colorectal neoplasms].

PMID- 14574886
TI  - [Colorectal cancers with both p16 and p14 methylation showing invasive
      characteristics].

PMID- 14574887
TI  - [Polymorphisms of matrix metalloproteinase (MMP)-1 and MMP-3 in colorectal
      cancer].

PMID- 14574888
TI  - [Immunohistologic evaluation of TS, DPD, and p53 protein expression in patients
      with colorectal cancer having liver and pulmonary metastases].

PMID- 14574889
TI  - [HLA-DR antigen expression of colorectal cancer cells and its significance in
      long-term survival].

PMID- 14574890
TI  - [Expression of hRFI in digestive system cancer].

PMID- 14574891
TI  - [Analysis of cell cycle inhibition by novel tumor suppressor gene Beclin 1 in
      human colon cancer cells].

PMID- 14574892
TI  - [General rules for management of cancer of the colon and the rectum].

PMID- 14574893
TI  - [Japanese General Rules and TNM System in the regional lymph node classification
      of colon cancer].

PMID- 14574894
TI  - [Clinicopathological features of colorectal villous tumors].

PMID- 14574895
TI  - [Multiple colorectal cancer and hereditary nonpolyposis colorectal cancer].

PMID- 14574896
TI  - [General considerations in nodule-aggregating lesions of the colon].

PMID- 14574897
TI  - [Treatment of colorectal carcinoma having submucosal invasion].

PMID- 14574898
TI  - [Outline of treatment for colorectal cancer].

PMID- 14574899
TI  - [Chemotherapy for colon cancer].

PMID- 14574900
TI  - [Molecular mechanism of drug resistance in colorectal cancer].

PMID- 14574901
TI  - [Evaluation of the response to treatment in colorectal cancer].

PMID- 14574902
TI  - [Adjuvant chemotherapy for colorectal cancer: Its efficacy and problems].

PMID- 14574903
TI  - [Molecular biological analysis of 5-fluorouracil sensitivity in colorectal
      neoplasm].

PMID- 14574904
TI  - [Response marker to 5-FU after curative surgery in colorectal cancer].

PMID- 14574905
TI  - [Application and problems in hepatic arterial infusion chemotherapy].

PMID- 14574906
TI  - [Home chemotherapy and outpatient treatment for metastatic colorectal cancer].

PMID- 14574907
TI  - [Paclitaxel for treatment of colorectal cancer].

PMID- 14574908
TI  - [Tegafur--preoperative treatment with tegafur suppositories for rectal cancer].

PMID- 14574909
TI  - [Doxifluridine for treatment of colorectal cancer].

PMID- 14574910
TI  - [Tegafur.uracil for treatment of colorectal cancer].

PMID- 14574911
TI  - [Intravenous continuous infusion of fluorouracil for treatment of metastatic
      colorectal cancer].

PMID- 14574912
TI  - [5-fluorouracil and leucovorin therapy for advanced colorectal cancer].

PMID- 14574913
TI  - [Irinotecan plus fluorouracil and leucovorin for advanced colorectal cancer].

PMID- 14574914
TI  - [Effect of systemic chemotherapy by 5-FU with low dose CDDP (in the hospital) and
      UFT with low dose CDDP (in outpatient clinic) in unresectable recurrent
      colorectal cancer].

PMID- 14574915
TI  - [Present status of chemotherapy for colorectal cancer in countries outside of
      Japan].

PMID- 14574916
TI  - [Toxicities associated with chemotherapy in colorectal cancer].

PMID- 14574917
TI  - [Complications of hepatic artery chemotherapy for liver metastases in colorectal
      cancer].

PMID- 14574918
TI  - [Surgical treatment of advanced colorectal cancer].

PMID- 14574919
TI  - [Indications for laparoscopic surgery in colorectal cancer].

PMID- 14574920
TI  - [Laparoscopic surgery for rectal and sigmoid colon cancer].

PMID- 14574921
TI  - [Recent trends in laparoscopic surgery for right side colon cancer].

PMID- 14574922
TI  - [Optimal length of resected colon and lymph node dissection for colon cancer].

PMID- 14574923
TI  - [Sphincter-saving operation for rectal cancer].

PMID- 14574924
TI  - [Lateral lymph node dissection for lower rectal cancer].

PMID- 14574925
TI  - [Transanal endoscopic microsurgery for early rectal cancer].

PMID- 14574926
TI  - [Optimal lymph node dissection for colon cancer].

PMID- 14574927
TI  - [New surgical procedure for preservation of anal function in very low rectal
      cancer].

PMID- 14574928
TI  - [Preoperative and postoperative radiotherapy for colorectal cancer].

PMID- 14574929
TI  - [Radiotherapy for locally relapsed rectal cancer].

PMID- 14574930
TI  - [Preoperative chemoradiotherapy for locally advanced rectal cancer].

PMID- 14574931
TI  - [Predictive factors of histologic effects in preoperative radiotherapy for rectal
      cancer].

PMID- 14574932
TI  - [Detrimental phenomena and their treatment in radiotherapy for rectal cancer].

PMID- 14574933
TI  - [Adjuvant chemotherapy for colorectal carcinoma after curative resection].

PMID- 14574934
TI  - [Preoperative radio/chemoradiotherapy in combination with intraoperative
      radiotherapy for stage II, III rectal cancer].

PMID- 14574935
TI  - [Long-term prognosis for colorectal carcinoma treated with adjuvant
      immunochemotherapy].

PMID- 14574936
TI  - [Significance of thermo-chemotherapy as tumor dormancy therapy for recurrent
      rectal cancer].

PMID- 14574937
TI  - [Preoperative chemo-radiotherapy for the treatment of advanced middle to lower
      rectal cancers].

PMID- 14574938
TI  - [Therapeutic approach for colorectal cancer with topoisomerase as a molecular
      target].

PMID- 14574939
TI  - [Intra-tumoral IL-6 down-regulation system as a new therapeutic target to control
      tumor growth in colorectal carcinoma].

PMID- 14574940
TI  - [Significance of thymidylate synthase and dihydropyrimidine dehydrogenase
      activity in colon cancer].

PMID- 14574941
TI  - [Combined treatment with fluorinated pyrimidines and selective cyclooxygenase-2
      inhibitors for liver metastasis of colon cancer].

PMID- 14574942
TI  - [Gene therapy for colon cancer].

PMID- 14574944
TI  - [Dominant negative IGF-I receptor ].

PMID- 14574943
TI  - [Suppression of cell growth in colorectal cancer by inhibition of telomerase].

PMID- 14574945
TI  - [Anti-proliferative effects of biochemical defense modifier antineoplaston in
      colorectal carcinoma].

PMID- 14574946
TI  - [Combination therapies using cyclooxygenase-2 inhibitors and angiotensin
      converting enzyme inhibitors in colon carcinogenesis].

PMID- 14574947
TI  - [Gene therapy for colon cancer targeting NF-kappa B].

PMID- 14574949
TI  - [Gene therapy for colorectal cancer in clinical trials].

PMID- 14574948
TI  - [Inhibitory effect of n-3 polyunsaturated fatty acids on colorectal cancers].

PMID- 14574950
TI  - [Surgery for colorectal cancer aimed at improving postoperative quality of life].

PMID- 14574951
TI  - [Endoscopic therapy for colorectal cancer].

PMID- 14574952
TI  - [QOL in elderly patients with colorectal cancer].

PMID- 14574953
TI  - [Guidance and informed consent in colon cancer therapy].

PMID- 14574954
TI  - [Treatment of elderly patients with colorectal cancer].

PMID- 14574955
TI  - [Psychological support of cancer patients and their relatives following informed
      consent].

PMID- 14574956
TI  - [Informed consent according to the stage of colorectal cancer].

PMID- 14574957
TI  - [Informed consent in the treatment of colorectal cancer].

PMID- 14574958
TI  - [Palliative care for colon cancer patients as total pain management].

PMID- 14574959
TI  - [Treatment for double cancer of the large intestine and stomach].

PMID- 14574960
TI  - [Management of obstructive colorectal cancer].

PMID- 14574961
TI  - [Treatment for recurrent colorectal cancer following endoscopic resection].

PMID- 14574962
TI  - [Treatment for recurrent colorectal cancer].

PMID- 14574963
TI  - [Treatment for small colorectal polyps].

PMID- 14574964
TI  - [Novel findings from an animal tourniquet shock model].
AB  - This article is a review of our experimental results regarding the physiological
      statuses and roles of chemical mediators in tourniquet shock, and a novel
      phenomenon, modulation reflex, that is commonly observed in this shock model is
      discussed. In a rabbit with a tourniquet applied to a hind limb for 24 hrs, blood
      pressure (BP) gradually falls after release of the tourniquet, but the decline in
      BP stops when a tourniquet is again applied to the hind limb, indicating that
      shock mediators are attributed to the hind limb. The levels of dipeptides
      (anserine and carnosine) and lysosomes in blood samples as well as the levels of
      leukotrienes (LTD4 and LTE4) in blood and muscle samples from rabbits in
      tourniquet shock were elevated. However, injection of a large amount of a
      dipeptide into an ear vein of a rabbit did not reduce BP, suggesting that both
      peptides may not be directly related with reduction in BP of rabbits in
      tourniquet shock. Injection of a platelet-activating factor (PAF) antagonist into
      an ear vein resulted in slight elevation of BP and the elevated level was
      maintained for about 1 to 4 hrs during the period of decline in BP in tourniquet
      shock. As for interleukin-6 (IL-6), IL-6-deficient mice at young ages have a
      significantly greater blood volume than do wild-type mice without concomitant
      changes in body composition. Therefore, the role for IL-6 in the regulation of
      peripheral circulation may be to elevate, not reduce BP. In mice in tourniquet
      shock, superoxide (O2-) production is observed in skeletal muscle cells and these
      cells correspond to mitochondria-rich cells. However, RT-PCR of muscle samples
      showed no significant nitric oxide synthase (NOS) mRNA expression after
      tourniquet release. Pretreatment with NOS inhibitors before tourniquet release
      reduced O2- production in the skeletal muscle. These results indicate that O2-
      produced in muscle subjected to ischemia/repefusion may be involved in shock. As
      for changes in mRNA expression patterns of pro-inflammatory cytokines and nerve
      growth factors in blood samples from rats in tourniquet shock, up-regulation of M
      CSF mRNA began at 2 h after tourniquet application and was short-lived. The level
      of ATF-3 mRNA had increased at 1 h and NGF mRNA gradually increased and reached a
      significantly high level at 4 h after tourniquet application. These results
      indicate that the transient mRNA expressions probably trigger secondary events
      that may be beneficial to wound repair and regeneration. In the early stage of
      tourniquet shock, the levels of IL-6 mRNA in the liver and kidneys of rats
      increased progressively and significantly, and the levels of iNOS mRNA in the
      kidneys increased. These findings suggest that that humoral and/or cellular
      mediators produced locally in the hind limb are responsible for remote organ
      injuries. Thus, these mediators, interacting each other, may contribute to the
      progress of shock. We have also found a novel phenomenon in tourniquet shock
      using rabbits. When a tourniquet is applied to the upper hind limb of a rabbit
      for 24 hrs, and pressure is applied to the femoral medial area immediately after
      tourniquet release, a reflex of decrease in blood pressure and decrease in heart
      rate, which last for a short period, is usually observed. This reflex is mediated
      through the ipsilateral femoral nerves, central nervous system and vagal nerves.
      Since the modulation reflex may be due to peripheral nerve injury, we
      investigated morphological and molecular changes in sciatic nerves and dorsal
      root ganglion (DRG) neurons in rats after tourniquet application. At 4 hr after
      tourniquet application, light microscopic examination showed only degeneration of
      the tourniquet segment in the sciatic nerve but no morphological changes in the
      DRG, while electron microscopic examination revealed mitochondrial swelling in
      some DRG neurons on the tourniquet-applied side and calcium deposition in these
      swollen mitochondria. These findings suggest that peripheral nerve injury induced
      a large amount of calcium influx into neuronal cell somas and that excess amounts
      of calcium-influx into neurons resulted in mitochondial swelling. Results of mRNA
      level analyses showed NGF mRNA expression followed by NGF protein expression in
      Schwann cells of the ipsilateral DRGs at 4 h after tourniquet application but not
      in the contralateral or control DRGs. Similarly, significantly high nNOS and iNOS
      mRNA levels were observed in the ipsilateral DRGs at 4 h, and expressions of nNOS
      and iNOS proteins were detected in the ganglion of the ipsilateral DRG. In
      addition, the TNF-alpha mRNA levels were significantly increased in the
      ipsilateral DRGs at 1 h after tourniquet application, indicating that TNF-alpha
      was activated in the early stage of nerve injury and then induced iNOS mRNA
      expression. Large amounts of nitric oxide (NO) produced by iNOS might result in
      damage to the host cells, and an overdose of NO might induce apoptosis and
      eliminate damaged cells during the early stage of nerve injury.

PMID- 14574965
TI  - [Development of new analytical technologies and their applications for forensic
      medical examinations].
AB  - Quantitation of drug concentration in a cell: Laser-induced photo-thermal
      microscopy and laser microscope (LSM) were used for quantitation of drug
      concentration in a cell of the fixed tissue sections. The colloidal gold labeled
      with antibodies was used as an indicator for detection of drugs or other
      antigens. The detection limit (10 zmol) of the tobramycin distributed in a
      epithelial cell of one renal tubule was 10-times superior to that of scanning
      laser microscope. The colloidal gold remained stable to laser-beam radiation and
      gave a low background. Therefore, the use of colloidal gold and laser microscopy
      make possible highly sensitive detection of drug in the fixed tissues. Highly
      sensitive quantitation of drug: A simple and highly sensitive time-resolved
      fluoroimmumoassay using a fluorescent europium chelate (4, 4'-bis (1", 1", 1",
      2", 2", 3", 3"-heptafluoro-4", 6"-hexanedion-6"-yl)-chlorosulfo-o-terphenyl
      (BHHCT)-Eu+3) was used for analysis of methamphetamine (MA). Two kinds of assay
      methods (one step assay and two step assay) using a microtiter plate coated with
      anti-MA were employed. The smallest measurable amounts of MA for the one-step and
      the two-step methods were 25 pg/assay and 25 fg/assay, respectively. Molecular
      biological approach to the forensic problem: a. The diagnosis of the death caused
      by drowning was possible by detection of the DNA fragments of aquatic plants from
      the organ of victims. The detection of the DNA fragments of chloroplast gene,
      ribose-bisphosphate carboxylase large subunit (rbcL), was performed using PCR
      method with the newly synthesized probes. b. Taq-Man probes were useful to
      perform the personal identification of many samples. Mitochondrial DNA analysis
      was also brought about good results for putrefactive samples. So, the combination
      of some examine methods was need for personal identification of multiple samples.
      DGGE method was also very useful and easy for multiple gene analysis for personal
      identification with SNPs.

PMID- 14574966
TI  - Effects of pupil diameter on light detection and temporal modulation.
AB  - PURPOSE: This study compared the effects of pupil variation on light detection
      and temporal modulation across the central visual field. METHODS: Light detection
      sensitivity (LDS) and low flickering frequency (6 Hz) temporal modulation
      sensitivity (TMS) of 20 young subjects were measured from the central visual
      field of the right eyes using an autumated perimeter (Medmont M600). The
      measurements were taken under 3 artificial pupils, i.e. 3 mm, 4.3 mm and 6 mm
      diameters. The sensitivities were grouped and averaged for different retinal
      eccentricities (3 degrees, 6 degrees, 10 degrees, and 15 degrees). RESULTS: TMS
      and LDS were reduced with increasing retinal eccentricities (P < 0.001) and
      decreasing pupil diameters (P < 0.001). TMS collected from all pupil diameters
      were significantly different from each other (P < 0.001). Similarly, LDS under 3
      mm pupil was statistically different from those of 4.3 mm and 6 mm (P < 0.003).
      Comparison of the hills of vision showed that pupil variation resulted in
      significantly different slopes (P = 0.001). The slopes were also found to be
      significantly different between TMS and LDS (P = 0.012). CONCLUSIONS: The data
      showed that dilated pupil resulted in significantly higher sensitivities than
      those of smaller pupil for both visual functions. The difference in the slopes of
      hills of vision also suggested that the variation in retinal illumination
      affected the visual responses differently at various retinal eccentricities for
      TMS and LDS.

PMID- 14574967
TI  - Removal of intralenticular magnetic foreign bodies with intraocular magnet.
AB  - PURPOSE: To investigate the possibility of conservation of the lens after removal
      of intralenticular magnetic foreign bodies with intraocular magnet. METHODS:
      Intralenticular magnetic foreign bodies of 15 patients were removed by using an
      intraocular magnet. The lens of each injury eye was conserved. Follow-up
      observation of these cases ranged from one to four years. RESULTS: The
      intralenticular magnetic foreign bodies of 15 patients were successfully removed.
      The lens of each injury eye was conserved and the transparence of the lens was
      properly maintained. Sizes of these foreign bodies were measured, ranging from
      0.3 mm to 3 mm in diameter. The follow-up observation showed that the corrected
      visual acuity of 14 cases was not changed after operation. CONCLUSIONS: The
      intraocular magnet is very helpful for removal of magnetic foreign bodies from
      the transparent lens. This magnet allows removing of the foreign body by the
      surgeon and no damage to the lens was induced during the operation. Thus,
      maintenance of visual acuity of most of the patients can be achieved.

PMID- 14574968
TI  - Preliminary clinical study on perforating prosthokeratoplasty.
AB  - PURPOSE: To observe the effects of perforating prosthokeratoplasty on patients
      with leucoma who failed in keratoplasty or were not suitable for keratoplasty,
      and improved their vision. METHODS: Five cases with leucoma (4 with chemical burn
      and 1 with blast) received Yakimenko Style keratoprosthesis implantation.
      Preoperative examination showed the visual acuity in 4 of the 5 cases was light
      perception, and that of the other one was FC/20 cm. The light orientation in 3
      patients was definite, and that in the other two was indefinite. RESULTS: The
      vision improved in 4 of 5 patients in the follow-up period of 9 months to 3
      years. Their visual acuity showed 0.09 to 0.8. And there was no change of vision
      in the other 1 case. CONCLUSIONS: Prosthokeratoplasty is the first choice for
      rehabilitation of the blind that have leucoma but are not suitable for or failed
      in penetrating keratoplasty.

PMID- 14574969
TI  - Comparison of the accuracy of Canon KU-1 IOL measurer and VPLUS A/B scanner in
      axial length measurement.
AB  - PURPOSE: To evaluate the accuracy of Canon KU-1 IOL measurer (Japanese Canon
      Company) and VPLUS A/B scanner (French Quantel Company) in axial length (AL)
      measurement. METHODS: Canon KU-1 IOL measurer and VPLUS A/B scanner were used to
      measure axial length of human cataractous eyes before cataract surgery. Two
      hundred and twenty-two cases (433 eyes) were involved. The results were compared
      and the postoperative visual acuity, refractive results were recorded during the
      follow-ups to evaluate the accuracy of the two instruments. RESULTS: In the 222
      cases (433 eyes), the absolute value of the measurement differences was 0.4 mm or
      above in 35 eyes, 0.8 mm or above in 17 eyes, 1.2 mm or above in 12 eyes, 2.0 mm
      or above in 5 eyes. The refractive error was less than 2.0 D in all patients. The
      mean values of ocular axial length by the two methods were 23.82 mm and 23.83 mm
      respectively and the difference had no statistic significance with compared t
      test (P = 0.902, two tail, alpha = 0.01). CONCLUSION: The accurate AL
      measurements can be obtained with the two instruments and the measurement results
      should be analyzed comprehensively to obtain accurate values in the complicated
      cases.

PMID- 14574970
TI  - Efficacy of 2% lidocaine injection as a topical agent in cataract surgery.
AB  - PURPOSE: To determine whether 2% Lidocaine injection is an effective topical
      anesthetic agent for non-phaco small incision cataract surgery. SETTING: Charity
      eye clinic supported by Hellen Keller International. METHODS: One hundred and
      twenty-five consecutive cataract surgery patients received topical anesthesia
      with 2% Lidocaine injection solution just 1 and 0.5 minutes prior to non-phaco
      small incision cataract extraction and intraocular lens implantation. Each
      patient was asked about pain or pressure sensation during the operation. RESULTS:
      The surgeon felt ease in the operations. Many patients (93/125) were comfort
      during the whole surgery. Only 9 patients' score was above level 3, mostly
      complained during the nucleus extraction; Among those whose score was level 1-2,
      82.6% (19/23) claimed discomfort at middle of the operation (nucleus extraction)
      or the beginning (creating the conjunctival flap). CONCLUSION: Lidocaine
      injection solution (2%) was an effective topical anesthesia agent in cataract
      surgery.

PMID- 14574971
TI  - The application of topical anesthesia combined with subconjunctival anesthesia
      for glaucoma surgery.
AB  - PURPOSE: To evaluate the feasibility, reliability and analgesia effect of topical
      anesthesia combined with subconjunctival anesthesia in anti-glaucomatous surgery.
      METHODS: Two hundred and four cases (357 eyes) underwent anti-glaucomatous
      surgeries under topical anesthesia with 0.5% Alcaine eye drops combined with
      subconjunctival anesthesia with 2% Lidocaine. The analgesic effect was analysed
      with visual analogue pain scale. RESULTS: Among all of 357 eyes, 62 eyes
      underwent peripheral iridectomy, 67 eyes underwent simple trabeculectomy, 167
      eyes underwent compound brabeculectomy and 12 eyes nonpenetrating trabecular
      surgery. The effects of anesthesia were as follows: 304 eyes (85.2%) were
      painless (Grade I), 50 eyes (14.0%) were slight painful (Grade II), and 3 eyes
      (0.8%) were more painful (Grade III) during surgery. And no severe complications
      were observed in all the cases during surgery and postoperatively. Amaurosis
      fugax was not observed in the glaucoma patients at the late stage with narrow
      visual fields and poor visual ability. CONCLUSION: Topical anesthesia combined
      with subconjunctival anesthesia is effective, safe and simple anesthesia
      alternative in routine anti-glaucomatous surgery, especially for the glaucoma
      patients at the late stage with narrow visual fields and poor visual ability. It
      is worthy of being applied widely.

PMID- 14574973
TI  - Amniotic membrane transplantation for conjunctival tumor.
AB  - PURPOSE: To evaluate the possibility of amniotic membrane transplantation (AMT)
      for the treatment of conjunctival tumor. METHODS: Preserved AMT was performed in
      26 patients (26 eyes) with conjunctival tumor, including 9 eyes (34.62%) with
      malignant tumor (conjunctival malignant melanoma, corneal and conjunctival
      squamous cell carcinoma, conjunctival lymphoma), 17 eyes (65.38%) with benign
      tumor (conjunctival papilloma, conjunctival dermoid tumor, conjunctival nevus,
      hemangioma etc.). RESULT: All the patients are followed up for 1-53 months. No
      acute rejection was observed after preserved AMT. Ideal healing was found in
      conjunctiva wound. CONCLUSION: Preserved AMT is a very effective method to repair
      wound after giant conjunctival tumor operation. Complete removal of tumor and
      perfect fixation are the key of ocular surface reconstruction.

PMID- 14574972
TI  - Study on ocular torsion of V patterns strabismus.
AB  - PURPOSE: To investigate the ocular torsion of V patterns. METHODS: Twenty-two in
      hospital V patterns patients underwent bilateral inferior oblique muscles
      myectomy for inferior oblique overacting and hortizon recti underwent recess
      resection procedure to correct hortizon devation. Objective cycloposition was
      assessed by fundus photograph before and 7 days after surgery in all cases. The
      photographs was stored in computer, and the disc-fovea angle was measured by
      means of drawing picture software. As well as the deviation, oblique muscle
      function was recorded before and after surgery. RESULT: Seventeen cases were
      bilateral ocular excyclotropia, 4 cases were monocular excyclotropia and one case
      was annual. The disc-fovea angle of right eyes and left eyes before operation is
      15.67 degrees +/- 5.72 degrees and 16.59 degrees +/- 6.69 degrees. The
      comparisons among V patterns and normal average showed significant differences (P
      < 0.001). The disc-fovea angle of right eyes and left eyes after operation is
      5.24 degrees +/- 5.87 degrees and 7.17 degrees +/- 5.40 degrees. There is no
      statistic difference between normal average (P > 0.5). The deviation between up-
      and down 25 degrees is 23.1 +/- 6.8 before surgery, as well as the one is 2.0 +/-
      2.25 one week postoperatively. All cases have bilateral inferior oblique
      overaction, and diminished but one case still has unilateral moderate overaction
      7 days after surgery. CONCLUSION: There is objective cyclotropia in case of V
      patterns, and the objective torsion is normal after weakening overacted inferior
      oblique muscles.

PMID- 14574974
TI  - A macular hole in a female adult with bilateral coats disease.
AB  - PURPOSE: To report a case of a macular hole in a female adult with bilateral
      Coats disease. METHODS: The fundus photograph, fundus fluorescein angiography
      (FFA) and indocyanine green angiography (ICGA) were performed in two eyes, and
      observed theirs characters. RESULTS: Fundus photograph showed massive yellowish
      white exudation in the temporal midperiphery of both eyes, but the degree was
      slighter in the right eye. There was 1/3 DD macular hole in left eye. FFA
      revealed general dilatation of capillaries, multiple aneurysms, and tortuous and
      closure of vessels in superotemporal midperiphery in both eyes, but the degree
      was slighter in the right eye. There was a one-third DD round transmitted
      fluorescence according the macula hole. ICGA revealed that hyperfluorescence of
      aneurysms in superotemporal midperiphery, the images of aneurysms were more
      clearly than in FFA. There was a 2/3 DD hypoflurescence of macula in the late
      phase of angiography. CONCLUSIONS: FFA and ICGA have respective advantage in
      revealing vascular abnormalities of Coats disease. Maybe there was some
      relationship between the abnormalities of retinal vascular and hypoperfusion of
      choroidial vascular in macula in this case.

PMID- 14574975
TI  - Changes of indocyanine green and fluorescein angiography in multiple evanescent
      White-dot Syndrome: a case report.
AB  - PURPOSE: To study the clinicopathological change on "Multiple Evanescent White
      dot Syndrome (MEWDS)" through fundus angiography analyses. METHODS: Examining the
      case with fluorescein angiography (FFA) and indocyanine green angiography (ICGA),
      visual field and following up for 15 months. RESULTS: There exist multiple white
      dots in the fundus photo and angiography. The changes on ICGA maintain longer
      than fundus photo and FFA. Papillae may be edematous and macula could present
      with special hypofluorescent flecks. CONCLUSIONS: MEWDS has specific angiographic
      features. Its pathological changes involve deep retinal pigment epithelium (RPE)
      as well as choroidal capillaries. The prognosis of the visual acuity for MEWDS is
      very good.

PMID- 14574976
TI  - Paracentral corneal dellen: a rare sign of Graves ophthalmopathy.
AB  - PURPOSE: To report a rare sign, paracentral corneal dellen that developed in a
      middle-aged female patient with Graves ophthalmopathy. METHODS: A paracentral
      corneal dellen developed in the left eye in a 42-year-old woman who was diagnosed
      as Graves ophthalmopathy. The patient had remarkable upper eyelid retraction,
      upper eyelid lag and upward motility restriction. The Graves ophthalmopathy was
      classified as Grade IV according to NOSPECS classification. RESULTS: Local
      artificial tear film and 0.3% Tobramycin eye drops were administered to both
      eyes. Twenty-four hours later, the left corneal dellen disappeared. CONCLUSIONS:
      Graves ophthalmopathy can lead to paracentral corneal dellen because of severe
      upper eyelid retraction and upward motility restriction of the eye in spite of
      the lack of lagophthalmos. Artificial tear drop and antibiotic eye drop therapy
      helped even though the patient did not have corneal exposure.

PMID- 14574977
TI  - Increased expression of intercellular adhesion molecule-1, vascular cellular
      adhesion molecule-1 and leukocyte common antigen in diabetic rat retina.
AB  - PURPOSE: To understand the expression and distribution of intercellular adhesion
      molecule-1 (ICAM-1), vascular cellular adhesion molecule-1 (VCAM-1) and CD45
      (Leukocyte Common Antigen) in the control nondiabetic and various courses of
      diabetic rats retina. To explore the role of adhesion molecules (AMs) and the
      adhesion of leukocytes to vascular endothelial cells via AMs in diabetic
      retinopathy (DR). METHODS: Sixty healthy adult male Wistar rats were randomly
      divided into diabetic groups (induced by Streptozotocin, STZ) and normal control
      groups. Rats in these two groups were further randomly divided into 3, 7, 14, 30,
      90 and 180 days-group, including 5 rats respectively. The immunohistochemical
      studies of ICAM-1, VCAM-1 and CD45 were carried out in the retinal digest
      preparations or retinal paraffin sections, and the results were analyzed
      qualitatively, semi-quantitatively. RESULTS: No positive reaction of VCAM-1 was
      found, and weak reactions of ICAM-1, CD45 were found in nondiabetic rats retina.
      The difference of 6 control groups had no statistical significance (P > 0.05).
      The increased ICAM-1 and CD45 staining pattern were detectable 3 days after
      diabetes induction, and a few VCAM-1 positive cells were observed in the retinal
      blood capillaries. The difference of diabetes and control is significant (P <
      0.05). Following the course, the expressions of ICAM-1, VCAM-1 and CD45 were
      increasingly enhanced, reaching a peak at the 14th day. CONCLUSION: Increased
      expression of ICAM-1, VCAM-1 and leukocytes adhering and stacking in retinal
      capillaries are the very early events in DR. Coherence of expression and
      distribution of the three further accounts for it is the key point for the onset
      of DR that AMs mediates leukocytes adhesion and endothelial cell injury.

PMID- 14574978
TI  - Experimental studies of melanin associated antigen and its relationship with
      sympathetic ophthalmia and Vogt-Kayanagi-Harada syndrome.
AB  - PURPOSE: To discuss the relationship of Bovine Melanin-Associated Antigen (BMAA)
      to Sympathetic Ophthalmia (SO) and Vogt-Kayanagi-Harada (VKH) syndrome. METHODS:
      BMAA was isolated and purified from bovine iris and ciliary body and MTT method
      was used to measure the peripheral lymphocyte reactions of SO and VKH syndrome
      patients to BMAA. 15 cases of SO were included in the SO group with 11 males and
      4 females. The average age was 37.5, ranging from 23 to 56 years; 15 patients
      with VKH syndrome were included in the VHK group with 7 males and 8 females.
      Their average age was 37.2 years, ranging from 24 to 69 years; 20 normal
      individuals without ocular and systemic autoimmune diseases were included in the
      control group. These included 9 males and 11 females, aging from 14 to 28 with an
      average of 23.8 years. RESULTS: The OD values of each group were as follows: SO
      controls 0.327 +/- 0.032; SO + BMAA 0.490 +/- 0.758; SO + PHA 0.5310 +/- 0.918;
      VKH controls 0.328 +/- 0.503; VKH + BMAA 0.430 +/- 0.530; VKH + PHA 0.328 +/-
      0.484; Normal controls 0.304 +/- 0.267; Normal + BMAA 0.343 +/- 0.326; Normal +
      PHA 0.477 +/- 0.598. The average OD values of peripheral lymphocytes to BMAA
      stimulation in SO patients and normal controls were 0.490 and 0.343 respectively.
      The difference was statistically significant, P < 0.001; The average OD values of
      peripheral lymphocytes to BMAA stimulation in SO and VKH syndrome patients were
      0.470 and 0.430 respectively. The difference was not statistically significant, P
      > 0.05. CONCLUSIONS: BMAA effectively stimulate the proliferative reaction of
      peripheral lymphocytes in SO patients and BMAA may act as an antigen and
      contribute in the pathological process of SO. No difference in proliferative
      reaction of peripheral lymphocytes was found between SO and VKH syndrome patients
      after BMAA stimulations and BMAA may be involved in the development of both SO
      and VKH syndrome.

PMID- 14574979
TI  - Study on retinal ganglion cell apoptosis after explosive injury of eyeballs in
      rabbits.
AB  - PURPOSE: To explore the pathological changes of retinal ganglion cell apoptosis
      and its relation to the value of glutamate concentration in vitreous body after
      explosive injury of eyeballs in the rabbits. METHOD: Similar explosive injury
      models of eyeballs in 10 adult grey rabbits were made. The rabbits were killed on
      scheduled time. The retinal tissues of studied eyes and control eyes were
      obtained for the pathological examination with TUNEL method respectively. The
      value of glutamate in vitreum of injured eyes was measured and was compared with
      that of contralateral eyes. Statistical comparison analysis on the experiment
      data was performed. RESULT: The value of glutamate in vitreum of injured eyes was
      significantly higher than that of contralateral eyes in all rabbits in the study.
      A lot of TUNEL positive cells were observed in the injured eyes. It suggested
      that apoptosis of the retinal ganglion cells took place. CONCLUSION: We speculate
      that apoptosis of the retinal ganglion cells is perhaps among the causes
      resulting in damage of visual function after explosive injury of eyeballs and
      that the increasing of the value of glutamate in vitreum possibly associated with
      apoptosis of the retinal ganglion cells.

PMID- 14574980
TI  - Different effects of topical prazosin and pilocarpine on uveoscleral outflow in
      rabbit eyes.
AB  - PURPOSE: To investigate the effects of topical prazosin and pilocarpine on
      uveoscleral outflow (Fu) in rabbits. METHODS: Sixteen rabbits were randomly
      divided into the control group (5 rabbits, only topical application of normal
      salino in the right eye of each rabbit), Prazosin (PZ) treated group (6 rabbits,
      only 0.1% Prazosin eyedrop 0.1% in the right eye of each one) and Pilocarpine
      (PC) treated group (5 rabbits, 1% Pilocarpine eye drop in each right eye).
      Intraocular pressure (IOP) of bilateral eyes of each rabbit was measured before
      and 1 h after topical application of the eye drop. And the bilateral eyes were
      perfused with Fluorescein-isothiocyanate bovine serum albumin (FITC-BSA) as the
      tracer into the anterior chamber of each rabbit for 30 min at 90 min after
      topical treatment. Then the rabbits were killed for Fu measurement. RESULTS: IOP
      of PZ-treated eyes decreased [(0.71 +/- 0.07)kPa] in 1 hour after PZ application.
      IOP of PC-treated eyes decreased [(0.70 +/- 0.08)kPa] in 1 hour after PC
      application. The average value of Fu was (0.176 +/- 0.048) microliter/min in
      control eyes. The average value of Fu in PZ-treated eyes was (0.339 +/- 0.018)
      microliter/min. The average value of Fu in PC-treated eye was (0.123 +/- 0.022)
      microliter/min. CONCLUSION: Both of PZ and PC can decrease IOP in rabbits
      following topical application. Topical PZ can increase Fu in rabbits and this is
      one of the mechanisms of PZ-induced IOP decrease. Topical PC can prevent Fu. PC
      decreases IOP not through uveoscleral pathway. This study demonstrates that
      uveoscleral pathway plays an important role in aqueous humor drainage. PZ may be
      a novel drug for decreasing IOP. FITC-BSA is an effective tracer for studying
      uveoscleral pathway.

PMID- 14574981
TI  - Downregulation of Nogo-A expression of oligodendrocytes in vitro with antisense
      oligodeoxynucleotides.
AB  - PURPOSE: To investigate the effect of antisense oligonucleotides (ODN) to Nogo-A
      mRNA expression in oligodendrocytes and to establish the base for further
      research of repair of optic nerve injury. METHOD: (1) Oligodendrocytes were
      obtained by inoculating the optic nerve of newborn (2 days) rats and were
      identified with galactocerebroside(GC) antibody immunocytochemical stain. (2) In
      order to observe the effects of antisense ODN on cultured cells, we set up five
      groups, including the groups of three concentration of antisense Nogo-A ODN (2
      microM, 5 microM, 10 microM), a group with the random sequence added to the
      medium and the control group. Reverse transcription-polymerase chain reaction (RT
      PCR) was adopted to study the effects of ODN on the expression of Nogo-A in
      oligodendrocytes. RESULTS: (1) Three days after inoculation, a few of round or
      fusiform shape cells migrated from optic nerve tissue; About 11 days later, the
      coverlips were completely covered by the cells; The cells identified with GC
      antibody immunocytochemical stain were positive cells. (2) The result of RT-PCR
      study showed that antisense Nogo-A ODN could significantly and specifically
      inhibit the expression of Nogo-A after 24 hours (P < 0.01). Random sequence has
      no effect on Nogo-A expression. CONCLUSION: Antisense Nogo-A ODN can effectively
      and specifically inhibit the expression of Nogo-A.

PMID- 14574982
TI  - Supply-saving initiative bucks local traditions.

PMID- 14574983
TI  - Foley prices edge downward.

PMID- 14574984
TI  - Internet use for buying reaches 'critical mass'.

PMID- 14574985
TI  - [Study on transgenic elite indica container line D297B containing foreign insect
      resistant gene gna].
AB  - It was reported in this article that the transgenic elite indica container line
      D297B containing snowdrop lectin (Galanthus nivalis agglutinin, GNA) gene gna was
      obtained by biolisties. PCR, Southern blotting and Western blotting indicated
      that the transgenes were integrated into the genome of D297B and expressed in
      transgenic plants. Analysis of protein activity showed that product of transgene
      had activity of agglutinin. Resistance of transgenic seeds to Hygromycin B
      suggested that the transgenes were integrated in a single locus and inherited
      according to the pattern of 3:1 in most of transgenic plants. In addition, the
      PCR analysis revealed that the insect-resistant gene gna and selective marker
      gene hpt were co-integrated and co-inherited.

PMID- 14574986
TI  - [In situ distribution and configuration of rDNA in the nucleolus of Pisum
      sativum].
AB  - Distribution and configuration of nucleolar DNA in the nucleolus of pea (Pisum
      sativum) were analyzed using cytochemical NAMA-Ur DNA specific stain method. The
      results showed that nucleolar DNA distributed in FC and juncture of FC/DFC in the
      forms of surrounding FC. rDNA in different positions existed in either condensed
      or uncondensed forms. Nucleolus-associated chromatin outside nucleolus extended
      in the periphery of FC via channels in the nucleolus.

PMID- 14574987
TI  - [Regulation to curd morphogenesis and genetics of exogenous BoCAL gene in
      cauliflower].
AB  - Cauliflower (Brassica oleracea var. botrytis L.) and cabbage (B. oleracea var
      capitata L.) are two varieties of species B. oleracea. Cauliflower BobCAL gene
      losses the original function due to its terminated mutation while cabbage BoCAL
      gene has the complete function. We obtained cauliflower plants transgenic for
      BoCAL gene using Arobacterium-mediated transformation. Genetic analysis of T2
      generation indicated that all cauliflower plants transgenic for BoCAL failed to
      form curd and produced the green, loosed inflorescences composed of flower buds
      instead, demonstrating that cauliflower BobCAL was complemented by cabbage BoCAL,
      and thus transgenic cauliflower lost the ability to form curd. Selfing of these
      transgenic plants gave rise to the similar inflorescence phenotype of T3 plants
      except 15 days delay of inflorescence appearance compared with the plants of T1
      generation. When transgenic cauliflower was crossed with wild-type cauliflower,
      the progenies formed the curd with a few of flower buds, and they delayed
      inflorescence onset till 135 days after sowing.

PMID- 14574988
TI  - [The mutation character of the RET proto-oncogene in Chinese patients with
      Hirschsprung's disease].
AB  - To clarify the pathogenesis of Hirschsprung's disease (HD) on molecular level and
      to reveal the relationship between the RET proto-oncogene and Chinese patients
      with HD, the mutations of the RET proto-oncogene were studied in 50 Chinese
      patients with HD and 30 normal children with an obstipation as control. Genomic
      DNA was extracted from venous blood of the HD patients and the normal children.
      Polymerase chain reaction (PCR) products, which were amplified using specific
      primers (RET; exon13), were electrophoresised to analyze the single-strand
      conformational polymorphism (SSCP) patterns. DNA sequences of exon 13 of the RET
      proto-oncogene were determined in patients showing abnormal SSCP bands. And then
      the familial tracking research was done for the patients with Exon 13 mutation.
      In 50 HD patients, seven cases were found with apparently abnormal SSCP bands.
      And three point mutations were proved by DNA sequencing. In the parents of seven
      HD patients with Exon 13 mutation, two patients' fathers had the same mutation as
      their children. The results suggest that the mutation of the RET proto-oncogene
      may have a high freqency in Chinese patients with HD, especially the heterozygous
      point mutation. And HD has the heredity tendency.

PMID- 14574989
TI  - [Expression and clinical significance of VEGF-C mRNA and CD 31 in esophageal
      squamous cell carcinoma].
AB  - To investigate the expression of vascular endothelial growth factor-C (VEGF-C)
      mRNA and CD 31 in esophageal squamous cell carcinoma (ESCC) and its promotion of
      lymphatic metastasis. The expression of VEGF-C mRNA was examined in 43 ESCC by in
      situ hybridization. Intratumoral microvessel density (MVD) was assessed by
      immunostaining endothelial cells, using anti-CD31 antibody. The positive rate of
      VEGF-C mRNA expression was 41.86%. The average rank of MVD was 76.36 +/-
      20.30/mm2. VEGF-C mRNA expression correlated significantly with lymph node
      metastasis, TNM stage and depth of invasion (p < 0.05 or p < 0.01) in statistic,
      but not with histological grade (differentiation) (p > 0.05). MVD correlated
      significantly with lymph node metastasis and TNM stage (p < 0.05) in statistic,
      but not with depth of invasion and histological grade (differentiation) (p >
      0.05). MVD was significant higher in the VEGF-C positive tumors than negative
      tumors (p < 0.05). The present study indicated that VEGF-C might play a role in
      lympatic metastasis via lymphangiogenesis and angiogenesis in ESCC.

PMID- 14574990
TI  - [Improved camptothecin production by cell lines of Camptotheca acuminata].
AB  - The concentration of camptothecin was determined in different tissues of
      Camptotheca acuminata seedling. The concentrations of camptothecin in new leaves
      and roots were significantly higher than in other tissues. However, the
      concentration of camptothecin declined with leaves becoming old. The induction of
      callus and cell suspension cultures from younger leaves of Camptotheca acuminata
      was observed. Cell lines were selected with improved camptothecin production as
      0.02%.

PMID- 14574991
TI  - [Comparison of vitrification cryopreservation among different stages of mouse
      embryos].
AB  - The cryopreservation of different embryo stages collected from ICR, C57BL/6 and
      F1 of DBA*C57BL/6 was carried out by using vitrification method. The morphology,
      in vitro development and birth rates of these embryos were compared after frozen
      thawed. The results showed that more than 75% of the morphology from 2-cell
      embryos to morula stages from different strains was normal, the normal morphology
      rates of 8-cell embryos being the highest, while those of blastulas being the
      lowest. The in vitro development rates became higher as the embryos developed.
      The morphology of in vivo and in vitro fertilized frozen 2-cell embryos showed no
      difference, but the development rate of in vivo fertilized frozen 2-cell embryos
      was significantly higher than that of in vitro ones. Embryos that underwent 3
      times frozen-thawing remained normal morphology. The pregnant rate and birth rate
      of frozen 2-cell embryos after embryo transfer were 64% and 40% respectively, but
      lower than those of fresh 2-cell embryo transfer.

PMID- 14574992
TI  - [The localization and the sexual differences of substance P in vocal control and
      part auditory nuclei of Carduelis spinus].
AB  - The expression of substance P in the vocal control and auditory nuclei was
      investigated by wsing immunohistochemical methods, and the gray density of
      numerical value was measured with the image processing system in females and
      males of Carduelis spinus. Then, the distribution and the gray density of
      substance P were compared between males and females. The results indicate that:
      1) Substance P labeled terminal and part cells were distributed in the Area X; 2)
      Substance P labeled cells were distributed in the nucleus high vocal center
      (HVc), magnocellular nucleus of the anterior neostriatum (MAN), robust nucleus of
      the archistriatum (RA) and dorsolateral nucleus of the anterior thalamus (DLM);
      3) Substance P labeled terminal and fibers were distributed in the vocal control
      nuclei such as nucleus dorsalis medialis (DM) and the nucleus hypoglossi, pars
      tracheosyringealis (nXI-Its), and in the auditory nuclei such as the nucleus
      ovidalisashell (Ov shell), the shell regions of mesencephalicus lateralis, pars
      dorsalis (MLd shell) and the nucleus intercollicularis (ICo). The values of gray
      degree of substance P labeled cells or fibers were significantly higher in males
      than that in females. The present study indicates that the distribution of
      substance P exhibits significantly sexual difference in the songbird. The
      presence of substance P in most auditory and vocal control nuclei suggests that
      substance P may play an important physiological role in the auditory perception
      and vocal production.

PMID- 14574993
TI  - [A simple and highly efficient Agrobacterium-mediated rice transformation
      system].
AB  - A simple and highly efficient rice transformation system was established based on
      the studying of factors influencing the Agrobacterium-mediated rice
      transformation. Embryogenic calli derived from mature embryos were infected and
      cocultivated with A. tumefaciens EHA101 harboring binary vectors: pHQ9, pHQ10,
      pHQT3. The highest transformation frequency was about 100 hygromycin resistance
      calli per gram of calli explants, and above 85% of these calli could be
      regenerated into plants. The putative transgenic plants were confirmed by GUS
      assay and southern-blot analysis. Hygromycin resistance tests indicated that the
      segregation of transgene in T1 progeny corresponded to the Mendelian ratio, 3:1.
      This system will benefit the functional genomic study of rice by using T-DNA
      insertion mutagenesis and gene targeting.

PMID- 14574994
TI  - [The distribution and origin of P elements in Drosophila melanogaster strains
      from northeast China].
AB  - Eukaryotic transposable elements, especially P transposable elements of
      Drosophla, are very important to study the evolution of biology. We collected 130
      single--female lines of D. melanogaster from 13 places in Northeast China and 3
      places nearby which are Beijing(BC), Yantai (YT), Huhehaote(HHT) in 1999 and
      2000. We amplified the fragments from ORF2 to ORF3 of P elements using PCR and
      calculated the defective frequencies and defective parameters of P elements from
      different places. Basing on the distribution of defective P elements, we
      suggested the invasion route of P elements of D. melanogaster in Northeast China.
      The results indicate that the defective frequencies decrease from the frontier to
      the inland, and in the isolated places the frequencies are lower. It is proposed
      that P elements of D. melanogaster in Northeast China originate from Korea and
      Russia to the frontiers of P.R. China, then expand into the inland.

PMID- 14574995
TI  - [Changes and distribution of ATPase activity in the paranodules of Nicotiana
      tabacum].
AB  - Lead phosphate deposition technique was used to investigate the changes and
      characteristic distribution of ATPase activity in the paranodules of tabacoo. We
      found that ATPase activity was closely associated with cell type and cell
      developmental state, thus it was different in various cells and rhizobia. No lead
      phosphate granules were located in the menstematic cells, although there were a
      small number of lead phosphate granules in the cytoplasm and organelles of the
      cells without rhizobia, they did not exist in the young and mature rhizobia. On
      the contrary, upon the senscence of the cells and rhizobia, a large number of
      lead phosphate granules appeared on the plasmalemmas and in the cell walls and
      the inside surfaces of the rhizobia. When the cells and rhizobia progressively
      senesced, lead phosphate granules increased in number, and they were widely
      distributed on the tonoplasts, plasmalemmas, cell walls, intercellular layers and
      in the intercellular spaces. At the same time, they also appeared on the surfaces
      and in the cytoplasm and nucleoids of the rhizobia. Due to cell disintegration,
      lead phosphategranules obviously decreased in number, they were only located on
      the plasmalemmas and membrane-vesicular structures which came from disintegrated
      organelles.

PMID- 14574996
TI  - [Localization of EGFP-DPF-1 expressed and secreted by HeLa cells in oocytes].
AB  - The eukaryotic expression plasmid pEGFP-N1/DPF-1 was constructed through fusing
      rabbit oviduct-specific glycoprotein (DPF-1) gene to the 5' terminus of eGFP
      gene. After transfecting the recombinant plasmid into HeLa cells, we got some
      cell strains expressing and secreting eGFP-DPF-1 stably. The apparent molecular
      weight of the fusion protein was up to 120 KD indicating the fusion protein was
      modified. Rabbit oocyte-cumulus cells complexes (COC), the cumulus cells-deprived
      oocytes or oviductal oocytes were co-cultured with the cell strain or cultured in
      the conditioned medium derived from the cell strain to observe the distribution
      of DPF-1 in oocytes after incubation. The results revealed that DPF-1 but not GFP
      alone associated with zona pellucidae (ZP) of oocytes, especially in the inner
      layer of ZP, and was evenly distributed in dot-like shape on the outer surface of
      the cytoplasmic membrane. In contrast, the cumulus cells around the oocyte did
      not interfere the association of DPF-1 with oocyte, and no trace of DPF-1 was
      found in the cumulus cells. The experiment proved that the oviductin expressed
      and secreted by eukaryotic cells in vitro could bind to oocytes, and was directly
      observed by using green fluorescent protein as a tracer. These results provided
      some interesting informations for the further studying on the functions of the
      oviductin.

PMID- 14574997
TI  - [Analysis of false-positive associated with antibody tests for SARS-CoV in SLE
      patients].
AB  - To discuss the false-positive of serological diagnostic testing for coronavirus
      antibody in patients with systemic lupus erythematosus(SLE), 66 normal individual
      and 31 SLE with non-SARS patients were detected for SARS-associated coronavirus
      (SARS-CoV) antibody and RNA by enzymelinked immunosorbent assays(ELISA) and
      reverse transcriptase-polymerase chain reaction(RT-PCR). The result showed 2/66
      cases(3.0%) were positive of SARS-CoV-IgG antibody and 66 cases were negative of
      SARS-CoV-IgM antibody in the 66 cases healthy controls; in 31 cases with SLE,
      positive rates of SARS-CoV-IgG and IgM antibody were 58.1% (18/31) and 29%
      (9/31), respectively, in which 7 cases(22.6%) were positive of both SARS-CoV-IgG
      and IgM antibody. All samples of positive SARS-CoV-IgG and IgM antibody were
      negative by RT-PCR. The ELISA kit coated by non-purification antigen may induce
      the false-positive of SARS-CoV antibody in patients with SLE. This result
      suggested that the specificity of ELISA tests for SARS was excellent and has low
      false-positive rates when using SARS-CoV-IgG and IgM antibody tests. A possible
      cause of false-positive of SARS-CoV-IgG and IgM antibody in SLE patients is
      coated antigens with SARS-CoV and Vero-E6 cells in ELISA methods.

PMID- 14574998
TI  - [Tissue culture and plant regeneration of Helianthemum songaricum Schrenk].
AB  - The cotyledonary segments of sterile seedlings of Helianthemum Songaricum Schrenk
      were cultured on different media containing different phytohormons. It was found
      that the calli could be induced efficiently on MS basal medium supplemented with
      10.0 mg/L NAA and 0.2 mg/L 6-BA. When calli were transferred on MS medium with
      2.0 mg/L 6-BA and 0.2 mg/L NAA, shoots were produced. The frequency of shoot
      differentiation reached about 85%. The regenerated shoots were rooted on 1/2MS
      medium added with 0.5 mg/L NAA. The rooting rate was about 76%. Regenerated
      plantlets were successfully transplanted in soil, with a success rate of 67%.

PMID- 14574999
TI  - [Minimal residual disease in childhood acute lymphoblastic leukemia: diagnosis of
      the 21 century].
AB  - The detection of very low numbers of leukemic cells persisting after treatment,
      i.e. the monitoring of minimal residual disease (MRD) is of significant clinical
      value for children with acute lymphoblastic leukemia (ALL). Particularly, the
      assessment of early response to remission induction treatment has high prognostic
      value and enables more reliable definition of low-risk and high-risk patient
      groups. This forms the basis for treatment modification in new treatment
      protocols. The predictive value of MRD monitoring is particularly clear after
      first relapse. It enables recognition of low-risk patients with low MRD levels
      (probability of relapse-free survival (RFS) of 86%), whereas high MRD levels in
      high-risk patients are predictive of dismal outcome (probability of RFS of 0%).
      Moreover high MRD positivity before stem cell transplantation is strongly
      prognostic of relapse after transplantation.

PMID- 14575000
TI  - [The problems of immunological diagnosis of childhood acute leukemia and non
      Hodgkin's lymphoma].
AB  - The immunophenotyping of leukaemia and non-Hodgkin's lymphoma cells is based on
      staining the cells with monoclonal antibodies against surface and cytoplasmic
      determinants followed with flow cytometry analysis. The problems of immuno
      phenotyping are associated with technical difficulties, changes in expression of
      determinants and the rare types of leukaemia and haematological disorders typical
      for newborns and infants. The lack of blast cells within cell suspension obtained
      for test may be the result of bone marrow disorder (aplastic anaemia,
      preleukaemic cytopenia) or technical pitfall. The changed expression of
      determinants on blastic cells observed as weak expression or overexpression or
      atypical combination of determinants requires a careful interpretation. In the
      diagnosis of rare types of acute leukaemia (e.g. erythroleukaemia,
      megakaryoblastic leukaemia, mixed lineage or undifferentiated leukaemia) the
      additional monoclonal antibodies beyond routine set are needed. A special concern
      is necessary in diagnosis of newborns and infants leukaemia or bone marrow
      disorders like myelodisplastic syndrome particularly in children with other
      systemic diseases e.g. congenital immunological deficiencies, Down's syndrome.
      The problems of immunophenotyping in non-Hodgkin's lymphoma are frequently
      associated with obtaining a representative material e.g. surgical tumour biopsy,
      lymph node. In some case the differential diagnosis including small round cell
      tumours and anaplastic type of lymphoma is necessary what requires an additional
      set of monoclonal antibodies. Despite of modern technology, morphology,
      immunophenotyping and histopathology remain the standard of complex diagnosis of
      lymphoproliferative diseases and haematopoietic disorders in children.

PMID- 14575001
TI  - [Leukemia in neonates and infants].
AB  - Leukemia diagnosed during the first year of life is a rare but highly malignant
      disease of hematopoietic system. In contrast to leukemias diagnosed after the
      first year of life, infant leukemia is characterized by distinct biological and
      genetic features, which influence the clinical course and disease outcome.
      Approximately 60% of acute leukemias in infants are associated with aberrations
      of chromosome 11q23 with the rearrangement of the MLL gene. Despite major
      progress in treatment of childhood leukemias, prognosis of infant leukemia
      (particularly in acute lymphoblastic leukemia--ALL) remains poor. The most
      unfavorable prognostic factors in infant ALL are age at diagnosis below 6 months,
      CD10 negativity, myeloid antigen co-expression, presence of MLL gene
      rearrangements and in particular poor response to steroids. Long-term event free
      survival (EFS) in infant ALL ranges from 20 to 40%, depending on treatment
      protocol. Slightly better results are achieved in infant acute myeloid leukemia.

PMID- 14575003
TI  - [Efficacy of idarubicin in the treatment of childhood acute non-lymphoblastic
      leukemia: report of Polish Pediatric Leukemia/Lymphoma Study Group].
AB  - Results of treatment of childhood ANLL remained unsatisfactory for a long time,
      and introduction of a new drug seemed justified as the EFS achieved in this
      disease between 1993-97 was 42%. In 1998 a new protocol containing idarubicine in
      dose 12 mg/m2 (each dose regardless of treatment phase) was introduced. Between
      1998 and 2001, 137 children with ANLL were referred to nine participating centers
      of PPLLSG. Thirty nine were uneligible, so 98 were evaluated. Among them 56 were
      qualified to standard risk group (SRG) and 35 to high risk group (HRG). In 7
      children the risk group was not established due to early death. Remission rate
      was 79% in the whole group and 98% and 63% in SRG and HRG, respectively. The
      actuarial 3-year overall survival (OS), 3-year event-free survival (EFS) and 3
      year event-free interval (EFI) are respectively: In the whole group 61%, 54% and
      67%; in SRG 81%, 70% and 71%; in HRG 40%, 40%, and 53%. CONCLUSIONS: Due to
      introduction if idarubicine significant improvement of the results was achieved
      in SRG (better OS, EFS and EFI). Better new treatment methods are required in
      HRG.

PMID- 14575002
TI  - [Advances in the treatment of children with high risk acute lymphoblastic
      leukemia (ALL) treated with modified "NEW YORK" protocols between 1987 and 2002].
AB  - From 1981 to 1986, in children with ALL and initial WBC > or = 50,000/mm3, over 6
      year disease-free survival was significantly lower (33%) than in children with
      WBC < 50,000/mm3 (60%). In attempt to improve this unsatisfactory results, three
      modified American protocols named: "New York", "New York I", and "New York II",
      "New York I", and "New York II" were introduced consecutively in the centers of
      Polish Pediatric Leukemia Lymphoma Study Group (respectively, in 1987, 1997, and
      1999). The treatment results achieved in three consecutive therapeutic groups of
      children with ALL and initial WBC > or = 50,000/mm3: group I--213 children (1987
      1996), group II--58 children (1997-1999), and group III--52 children (1999-2001)
      are presented. The observation was completed in December 31, 2002. In three
      evaluated groups the first complete remissions (CRs) were achieved in 90.6%.
      94.8%. and 94.2% of patients, respectively. Relapses occurred in 71 patients of
      group I (37%), in 9 patients of group II (16%), and in 6 patients of group III
      (12%). The complications of treatment caused death in 7 children of group I, in 1
      child of group II, and in 2 children of group III. Eighty-one (38%), 11 (18.9%),
      and 9 (17.3%) patients, respectively, died due to progression of disease. The
      event-free survival (EFS) in three evaluated groups did not depend on age of
      children and WBC. The rates of 2-, 5-, and 10-year event-free survival (EFS) in
      group I were: 69.9%, 55.3%, and 53.6%, respectively and the rates of 2- and 5
      year EFS in group II were: 80.7% and 72.7%, respectively. The rate of 2-year EFS
      in group III was 71.6%. The analysis of achieved treatment results in three
      evaluated groups shows the gradual improvement of the prognosis in children with
      ALL and initial WBC > or = 50,000/mm3 treated with the use of modified protocols
      "New York" and "New York I" in comparison with patients treated before 1987.
      Longer observation is needed for evaluation of efficacy and complications of "New
      York II" protocol.

PMID- 14575004
TI  - [Neuroblastoma: epidemiology, pathomorphological and molecular diagnosis,
      prognosis].
AB  - Neuroblastoma is the third most common neoplasm of childhood. About 70% of cases
      occurs by 5 years old and around 95% cases in the patients younger than 10 years
      old. Neuroblastoma is part of the spectrum of the family neuroblastic tumors. The
      family consists of heterogeneous group of tumors, difficult to classify.
      Additionally some cases of neuroblastoma show tendency to self-maturation and
      regression. The family consists of neuroblastoma (NB), ganglio-neuroblastoma
      (GNB) and ganglineuroma (GN). In recent years there has been considerable
      development in the classification concepts from purely histological to clinico
      pathological one. These schemes include clinical, pathological and molecular
      features od tumors which allow more accurate prognostication.

PMID- 14575005
TI  - [Brain tumors in children].
AB  - Primary central nervous system (CNS) neoplasms are the most common solid tumors
      in children. During the last two decades progress in diagnostic procedures and
      treatment has been made. New techniques of imaging (CT, MRI), neurosurgery,
      intensive care and the introduction of intensive chemotherapy and refined
      radiotherapy had the greatest impact on this progress. Nevertheless, out of all
      pediatric malignancies this group of patients has the worst prognosis. To improve
      survival optimal treatment modalities are searched for. This paper presents brain
      tumors epidemiology, etiology aspects, classification, clinical symptoms,
      diagnostic procedures and current treatment strategies in CNS tumors in children
      such as: medulloblastoma/PNET, high and low grade gliomas, ependymomas, germ cell
      tumors and brain stem tumors. Age of the patients is considered in all tumors as
      there is a specific philosophy of treatment in small children. We are also
      presenting directions of recent clinical trials and the aims of pediatric
      oncologists in improving the effectiveness of treatment and quality of life of a
      cured child.

PMID- 14575006
TI  - [Indications for hematopoietic stem cell transplantation in pediatric oncology
      and hematology in the year 2003].
AB  - Indications for hematopoietic stem cell transplantation in children with
      oncological diseases as well as in children with congenital and acquired
      nonmalignant diseases have been reviewed in context of diagnosis, stage of
      disease, timing and type of transplant.

PMID- 14575007
TI  - [Dendritic cells in child neoplastic disease].
AB  - Dendritic cells (DC) are important antigen-presenting cells (APC) of immune
      system that induce and modulate primary and secondary immune responses; they also
      induce of central and peripheral tolerance T lymphocytes to self-antigens. They
      interact with T, B and NK cells and promote activation, differentiation and
      effectory functions of these cells. The total number of 91 patients: 53 males and
      38 females, aged from 1 month to 18 years (median 9 years) treated in the
      Department of Children Bone Marrow Transplantation, Oncology and Hematology,
      Medical University of Wroclaw, Poland (ALL--39, AML--15, NHL--8, HD--10, LCAL--4,
      solid tumors--15 children) were examined. Peripheral blood was collected at time
      of diagnosis, during chemotherapy, at time of relapse or progression disease and
      analyzed with used flow cyto-metric analysis. The subpopulations of CD were
      examined with use of specific markers for distinct blood dendritic cell
      populations: BDCA1 BDCA2, BDCA3 (Miltenyi Biotec). Both of activated DC CD83+ HLA
      DR+ and lymphocytes T CD3+CD26+ were stained of monoclonal antibodies CD83
      (Pharmingen), CD11c, HLA-DR, CD3, CD26, CD19 (BD Bisciencies). The results of our
      study showed increased level of blood DC in ALL and AML patients at time of
      diagnosis, relapse or during progressive disease in comparison with control group
      of healthy children, as well as in other patients. Those yields explained
      positive correlation with value of activated lymphocytes T (p < 0.05).

PMID- 14575008
TI  - [Bacterial infections in neutropenic patients with cancer].
AB  - This paper shows the predisposing factors for infection in neutropenic patients
      with cancer, and the use of antibiotics in empirical antibacterial therapy. The
      role of glicopeptide and the fourth generation of cephalosporis in monotherapy
      and dualtherapy in empirical treatment of febrile neutropenia is also discussed.

PMID- 14575009
TI  - [Viral infection in children with malignant diseases].
AB  - Infection, including viral infection, still cause serious complication in the
      course of chemotherapy. Recognition of viral infections, monitoring, prophylaxis
      and treatment is aimed at reducing the number of infected patients, mitigating
      the cause of the disease and limiting deaths directly linked with infections in
      paediatric cancer patients. Viruses from the herpes group (HSV, VZV, EBV, CMV)
      are particularly dangerous. They can cause not only asymptomatic and local
      infectious but also general diseases and can reactivate, especially after BMT.
      Hepatoropic viruses (HBV, HCV) often lead to breaks in chemotherapy, while
      chronic viral hepatitis can lead to fibrosis, cirrhosis and even primary
      hepatocellular carcinoma. CMV, RSV, adenovirus influenza and parainfluenza virus
      cause diffuse interstitial pneumonitis and are also associated with a high rate
      of mortality. In this paper, we present the most frequency viral infection in
      children with malignant diseases, their methods of diagnosis and treatment.

PMID- 14575010
TI  - [Azithromycin (Sumamed) administration in empiric treatment of nosocomial
      pneumonia in upper digestive tract cancer patients].
AB  - Septic complications are the most frequent and potentially lethal complications
      among patients treated for tumours. Respiratory tract infection, including
      pneumonia, is third most frequent of all infections occurring among patients
      undergoing surgical treatment. Of great clinical and pharmaeconomical importance
      is rational therapy with antibiotics, which lowers the risk of septic
      complications and sometimes even saves patients' lives. Azithromycin proved to be
      effective cure for environmental pneumonia. There has been presented a
      preliminary research on effectiveness of azithromicin in the treatment of septic
      pneumonia among patients treated for upper digestive tract cancers.

PMID- 14575011
TI  - [Development of new sensitizations to allergic components in birch pollen extract
      during specific immunotherapy].
AB  - Specific immunotherapy is the only currently available allergen-orientated
      treatment able to modify the natural history of respiratory allergic diseases.
      Safety and clinical efficacy of this treatment are well documented, but evidence
      about the ability to reduce new sensitizations is still poor. The authors
      describe the development of new IgE specificities to allergenic components in
      birch pollen extract during specific immunotherapy. A study was carried out in 12
      birch pollen-sensitive patients who received injection immunotherapy for 6
      months. Eight patients not submitted to SIT were used as a control. New IgE
      sensitizations to Bet v 2 developed in 25% of the birch immunotherapy-treated
      patients and the oral allergy syndrome additionally in one of them.

PMID- 14575012
TI  - [Cracovian program for secondary prevention of ischemic heart disease. Methods of
      intervention].
AB  - The Cracovian Program for Secondary Prevention of Ischaemic Heart Disease carried
      out in cooperation with the Cracow Branch of Polish Cardiac Society is the first
      and so far the only attempt in Poland to extensively assess the quality of care
      in terms of secondary prevention of ischaemic heart disease, at the same time
      trying to influence both the physicians and patients. The results of the 1st
      stage of the Cracovian Program conducted in 1997-98 indicate that the
      recommendations for secondary prevention of ischaemic heart disease are not
      implemented to a satisfactory degree during hospitalization in cardiology
      departments of university and general hospitals in Cracow, as well as in the post
      discharge period. Because of this, measures were undertaken to improve the
      quality of secondary prevention. Current recommendations for secondary prevention
      of ischaemic heart disease were presented and discussed during trainings for
      physicians from the participating centres and primary care physicians. At the
      same time the results of the 1st stage of the Cracovian Program were presented
      and the discrepancies between recommendations and everyday practice were
      identified. Two types of leaflets concerning secondary prevention were also given
      to patients discharged from the participating departments. In the 2nd stage of
      the Cracovian Program for Secondary Prevention of Ischaemic Heart Disease carried
      out in 1999-2000, the implementation of recommendations on secondary prevention
      was reassessed. The analysis of data obtained in the 2nd stage shows to what
      extent progress in research dealing with patients with ischaemic heart disease is
      reflected in everyday practice. It also allows for the evaluation of the impact
      of the above described intervention on the frequency of achieving the goals
      defined in the guidelines of cardiac societies. In this paper the genesis,
      outline and objectives of the project are discussed as well as the methods of
      intervention applied. The implementation of secondary prevention guidelines both
      during hospitalization and after discharge will be discussed in separate
      publications.

PMID- 14575013
TI  - [Cracovian program for secondary prevention of ischemic heart disease. Secondary
      prevention of ischemic heart disease during hospitalization in 1996-97 and 1998
      99].
AB  - INTRODUCTION: Hospitalization for ischaemic heart disease is a convenient moment
      to initiate pharmacological and non-pharmacological treatment as well as
      education of patients. The aim of the study was to assess the quality of medical
      care in the field of secondary prevention in patients hospitalized for ischaemic
      heart disease in cardiac departments of university and general hospitals in
      1998/99 as compared with 1996/97. MATERIAL: Consecutive patients were recruited
      on the basis of hospital records review of six cardiac departments (three in the
      university and three in general hospitals) in 1998/99. Inclusion criteria were:
      age < or = 70 years, inhabitance in the city of Cracow and its province and
      hospitalization due to: myocardial infarction, unstable angina, coronary
      angioplasty or coronary-aortic bypass grafting. METHODS: Hospital records of the
      included patients were reviewed. Data on previous history of ischaemic heart
      disease, on risk factors (including smoking, hypertension, diabetes,
      dyslipidemia, obesity) and drugs prescribed at discharge were obtained based on a
      predefined questionnaire. RESULTS: The frequency of blood pressure measurement in
      the first 24 hours of hospitalization was 88.8% in 1996/97 vs 95.7% in 1998/99 (p
      < 0.001). In the first 24 hours after admission total cholesterol concentration
      was measured in 32.8% and 45.0% of patients (p < 0.001), HDL cholesterol in 30.2%
      and 41.9% (p < 0.001) and triglycerides in 32.3% and 44.5% (p < 0.001),
      respectively. Both height and body mass were documented in 54.3% and 61.7% (p <
      0.05) of the reviewed charts. Antiplatelet drugs were prescribed at discharge in
      86.7% and 90.7% of patients (p < 0.05), beta-blockers in 66.4% and 61.9%, ACE
      inhibitors in 50.2% and 52.8%, while lipid lowering drugs in 27.1% and 41.6% (p <
      0.001), respectively. CONCLUSION: In 1998/99 compared with 1996/97 the quality of
      care in the field of secondary prevention of ischaemic heart disease was improved
      in cardiac departments of university and general hospitals in Cracow.

PMID- 14575015
TI  - [Adhesion molecules: atherosclerosis and coronary artery disease].
AB  - Inflammation is now considered a critical pathogenic component of the
      atherosclerotic process. The initiation and progression of atherosclerosis as
      well as the pathogenesis of clinical forms of coronary artery disease are
      mediated by cell adhesion molecules. Their activation is associated with risk
      factors for atherosclerosis. The most important developments related to cell
      adhesion molecules and cardiovascular disease are the recognition of a novel
      target for therapeutics. Moreover the serum levels of adhesion molecules seem to
      be markers of the risk for cardiovascular events.

PMID- 14575014
TI  - [Cracovian program for secondary prevention of ischemic heart disease. Secondary
      prevention of ischemic heart disease after discharge in 1997-98 and 1999-2000].
AB  - INTRODUCTION: Although most actions undertaken within the scope of the secondary
      prevention of ischaemic heart disease should be initiated during hospitalization,
      obtaining maximal effects (quantified by cardiovascular risk reduction) depends
      largely on continuation and appropriate adjustment of these measures in the post
      discharge period. The aim of this paper is to assess the implementation of
      guidelines on secondary prevention of ischaemic heart disease in the period after
      discharge from the hospital in the years 1999/2000 as compared with 1997/98.
      MATERIAL AND METHODS: In the first phase 515 subjects hospitalized in cardiac
      departments of university and general hospitals in Cracow were included. Out of
      them, 427 patients attended the control visit 6-18 months after index
      hospitalization. Based on a standardized questionnaire a structured medical
      history was obtained including the presence of risk factors and medication. At
      the same time body height and mass and blood pressure were measured and blood
      samples were obtained for lipid profile and fasting glucose level. RESULTS:
      Elevated cholesterol levels (> or = 5.2 mmol/l) were observed in 65.8% of
      patients in 1998/99 and 66.3% in 1999/2000, high blood pressure (> or = 140/90
      mmHg) in 46.2% and 50.4%, obesity (BMI > or = 30 kg/m2) in 24.6% and 27.2%,
      fasting hyperglycemia (> or = 6.0 mmol/l) in 17.7% and 27.4% (p < 0.05) and
      smoking in 16.3% and 15.9%, respectively. An increase was observed in the rate of
      antiplatelet (76.1% in 1998/99 vs 86.7% in 1999/2000, p < 0.001) and lipid
      lowering drug use (34.0% vs 41.9%, p < 0.05). The rate of beta-blockers and ACE
      inhibitors use did not change significantly. CONCLUSIONS: In the years 1999/2000
      the control of main risk factors of ischaemic heart disease did not improve when
      compared with 1997/98. There was only an increase in the percentage of patients
      on antiplatelet and lipid lowering drugs. These results indicate that the
      dissemination of the guidelines for secondary prevention of ischaemic heart
      disease among physicians and patients remains one of the top priorities of
      cardiology in Poland.

PMID- 14575016
TI  - [Asymptomatic carotid stenosis: ACS].
AB  - Asymptomatic carotid stenosis (ACS) is the lesion located in the vicinity of the
      common carotid artery branching, without neurological symptoms caused by
      insufficient blood flow to the brain. Cerebrovascular diseases represent an
      important medical as well as social problem, since this is one of the leading
      causes of mortality and serious invalidity worldwide. Majority of brain insults
      are caused by stenosing atherosclerotic lesions of the carotid arteries. Thus,
      early surgical treatment may contribute to lessen this problem. Routine diagnosis
      of ACS include auscultation and ultra-sonographic examination of carotid
      arteries. Early detection of the disease enables proper medical prophylaxis and
      decision for surgical treatment (providing that expected benefit for the patient
      exceeds possible operative risk, i.e. < 3% of complication rate in experienced
      surgical wards). That's why of particular importance is to formulate
      multidisciplinary programs of insult prevention and to conduct multiinstitutional
      studies in order to establish clear cut indications for surgical treatment,
      particularly for the group of asymptomatic patients.

PMID- 14575017
TI  - [The aging of the immune system].
AB  - As the expected lifespan of man still rises in modern societies, the problems of
      immunosenescence are getting constantly more and more interesting for scientists.
      According to the classical theory, cumulating microinjuries within the immune
      system cause overall immunodeficiency in elderly. However, recently the genetic
      background is more frequently used for explanation of this phenomenon. One of the
      main causes of immunosenesence is involution of the thymus. The results of this
      process are changes in subpopulations and functioning of T cells, as well as
      mainly secondary dysfunction of other types of immune cells. Although function of
      some cells (e.g. neutrophils or NK cells) seems to remain unaffected, the immune
      system in elderly is clearly less effective in comparison with the younger
      population. Hopefully, studies on this subject will help to find some effective
      strategies to prevent or to treat this dysfunction.

PMID- 14575018
TI  - [Patients compliance with antibiotherapy of respiratory tract infections].
AB  - Non-compliance frequently occurs during outpatient antibiotherapy of respiratory
      tract infections. The most frequent form of non-compliance in such circumstances
      is omittion of single doses. Patient non-compliance during antibiotherapy is of
      practical importance. It leads to therapy failure, need of additional health
      services, growth of direct and indirect therapy cost and development of resistant
      strains. This paper summarises the methods of evaluating compliance and the
      results of research on compliance during antibiotherapy of respiratory tract
      infections. The reasons of patient non-compliance as well as the factors
      influencing this phenomenon are reviewed. Practical methods of augmenting
      compliance are suggested with particular stress on the relationship between
      dosage frequency and compliance. It should be remembered that when the antibiotic
      is needed for respiratory tract infections treatment, once daily dosing ensures
      the best possible compliance.

PMID- 14575019
TI  - [Therapy of diabetic neuropathy].
AB  - A clinical state of peripheral and autonomic nerve damage in the abnormal
      environment of diabetes mellitus leads to syndromes of diabetic neuropathy.
      Diabetic neuropathy is a complication that affects most patients with
      longstanding diabetes mellitus, deteriorating their quality of life. The
      pathogenesis of diabetic neuropathy is multifactorial. The goals of treating
      diabetic neuropathy are to prevent the progression and reduce the symptoms.
      Smooth diabetes control without the risk of hypoglycaemia is most important to
      prevent progression. Early treatment is suggested, because of advanced marked
      nerve fiber loss. Treatments are supported by several investigations in diabetic
      patients: aldose reductase inhibition, prevention of protein glycation,
      improvement of nerve and administration of neurotrophic factors. Many other
      medications like amitriptiline, gabapentin, and carbamazepine have been used
      successfully in the treatment of painful diabetic neuropathy. To reduce the
      symptoms, studies have also shown analgesics to be effective.

PMID- 14575020
TI  - [Selected risk factors and primary prevention of colorectal cancer].
AB  - Incidence rates of colorectal cancer vary around 20-fold between industrialized
      and developing countries. Colon cancer is one of the most common cancers and very
      important public health problem in the Western world. Each year about 7000
      patients in Poland die from colorectal cancer. Most cases of this cancer are
      possibly related to lifestyle or environmental factors. It is estimated that
      about 13% of colorectal cancer is attributable to low physical activity, 12% to
      diet and about 10-15% to genetic susceptibility. The aim of this work was to
      analyze the relationship between diet, physical activity and colorectal cancer
      risk. Current data suggest that lifestyle modification including proper diet,
      regular physical activity and maintaining an appropriate body weight may lead to
      50-75% decrease of colorectal cancer cases. Therefore, effective management
      should include effective educational programs including dietary and other
      lifestyle behavior guidelines as well as early diagnostic of colorectal cancer.

PMID- 14575021
TI  - [Laparoscopic surgery of the large intestine].
AB  - Contemporary concepts regarding the use of laparoscopy in large bowel surgery
      were presented. Indications, contraindications and limitations of this technique
      were given. Operative technique of the most common procedures was discussed.

PMID- 14575022
TI  - [The decade of laparoscopic cholecystectomy].
AB  - The role of laparoscopy in the treatment of gallbladder stones has been
      discussed. Operative technique, intraoperative difficulties, complications and
      its treatment were presented. Indications, postoperative course, advantages and
      drawbacks of minimally invasive techniques in the treatment of cholelithiasis
      were discussed.

PMID- 14575023
TI  - [Exacerbation of aspirin-induced asthma associated with RSV infection].
AB  - We report the case of a 60 year old woman, suffering for 8 years from aspirin
      induced asthma, having an airway infection of RSV-respiratory syncytial virus.
      New methods of molecular biology were used to identify the virus in the lung
      bioptate (RT-PCR, reverse transcription polymerase chain reaction and nested
      PCR). The role of viruses, especially RNA, is still unknown in pathogenesis of
      asthma. The reported case could help to explain their participation in this
      disease.

PMID- 14575024
TI  - [Two cases of bacterial allergy caused by Staphylococcus aureus].
AB  - Bacterial respiratory tract infections often occur. The importance of bacterial
      allergy of the upper respiratory tract is one of the most controversial problems
      in allergology. The authors present two cases of bacterial allergy caused by
      hypersensitivity to staphylococcus aureus. Anti-S. aureus IgE antibodies were
      detected and the skin reaction to bacterial vaccine was also positive. Our
      observation suggests that immediate hypersensitivity to bacteria, for example to
      staphylococcus aureus may play a role in infection exacerbations.

PMID- 14575025
TI  - Genetic causes of human infertility.
AB  - The currently characterized chromosomal disorders and gene mutations that cause
      infertility in humans were reviewed. Of the four arbitrary compartments, genes
      expressed in the gonad comprise the most common site affected by mutations
      causing infertility. Clinicians should be aware of the most common causes that
      have clinical implications: (1) women with a 45,X cell line commonly have cardiac
      anomalies that may pose a risk for maternal death in pregnancies achieved by
      donor egg IVF; (2) men with Y-chromosome deletions may produce male offspring
      with the same deletion, rendering them infertile; (3) CBAVD must be ascertained
      in men with azoospermia because of the risk for having a child with CF; and (4)
      some women with premature ovarian failure may be fragile X syndrome carriers, so
      other family members may be at risk for the full syndrome. In the future, more
      genes will be identified to cause infertility in humans, which will translate
      into clinical significance. In select cases, in which the genetic defect is
      known, it may be possible to use preimplantation genetic diagnosis to screen
      embryos prior to uterine transfer.

PMID- 14575026
TI  - Impaired fertility caused by endocrine dysfunction in women.
AB  - Infertility can be frustrating for patients and physicians. Endocrine dysfunction
      can impair fertility and alter pregnancy outcome. Once the diagnosis is secured,
      most endocrine disorders are reversible or can be adequately managed to restore
      fertility and decrease associated pregnancy complications. Improved understanding
      of the subtleties and intricacies of mechanisms by which endocrinopathies can
      hinder fertility and influence the course of a pregnancy is vital, more so in the
      era of assisted reproductive technology, because pregnancy in an abnormal
      endocrine environment can be disastrous. The role of autoimmunity in infertility
      and pregnancy loss is less clear; in this context, there are limited management
      options to improve fertility and overall pregnancy outcomes.

PMID- 14575027
TI  - Recommendations of a National Working Group on Prevention and Control of Rabies
      in the United States. Article III: Rabies in wildlife. National Working Group on
      Rabies Prevention and Control.

PMID- 14575028
TI  - Counseling about sexuality in the older person.
AB  - The clinician's challenge is to help older individuals develop and sustain the
      intimate relationship that they desire. This involves active assessment and
      teaching on how to improve and continue their sexual health by actively reviewing
      health concerns and conditions that affect sexual functioning and libido. Older
      adults should be given information, education, and concrete direction to assist
      them in creating and sustaining intimate relationships. Older adults are
      increasingly vigorous with fairly good health and desire information and support
      to help them maintain their activity and sexuality. Health care providers should
      assist older adults in being sexually creative and understanding that there is
      more to a satisfying relationship than the purely genital approach. The refining
      of a more loving relationship includes encouragement of intimacy, sensualness,
      companionship, and friendship, as well as continued knowledge and understanding
      about the effects that one's health conditions, medications, and treatment have
      on sexuality and functioning.

PMID- 14575029
TI  - Psychiatry in pictures. Steve Blundell, number 15 Digital cry and number 24
      Stapled red.

PMID- 14575030
TI  - Jaspers was right after all--delusions are distinct from normal beliefs. Against.

PMID- 14575031
TI  - [Software-assisted modular process cost analysis for calculation of case costs].

PMID- 14575032
TI  - [Preservation of immune tolerance to avoid autoimmunity. The role of dendritic
      cells].

PMID- 14575033
TI  - [Skin aging].

PMID- 14575034
TI  - Vitellogenin hormonal control in the green frog, Rana esculenta. Interplay
      between estradiol and pituitary hormones.
AB  - 1. The effect of estradiol and pituitary hormones on the titre of serum
      vitellogenin has been studied in Rana esculenta by rocket immunoelectrophoresis.
      2. Hepatic synthesis of vitellogenin depends on physiological doses of estradiol.
      3. Gonadotrophins enhance the uptake, presumably by acting directly on the oocyte
      plasma membrane. 4. In addition, our data support direct pituitary intervention
      on liver synthesis and/or release of vitellogenin. 5. Hormonal response, as
      evaluated by vitellogenin serum titres, tends to increase from November to July.
      This could be the expression of a modification, throughout the sexual cycle, of
      liver sensitivity to the hormones.

PMID- 14575035
TI  - Endocrine-related resources from the National Institutes of Health.

PMID- 14575036
TI  - [The dysplastic nevus. Separate entity, melanoma precursor or diagnostic
      dilemma?].
AB  - Today, 20 years after Clark and Elder postulated their tumor progression model of
      melanocytic lesions from common nevi to melanoma, there are still controversies
      surrounding this subject. Despite modem molecular biological developments, a
      consensus about the question, if the dysplastic nevus should be considered as a
      separate entity, melanoma precursor or just represent a diagnostic dilemma, still
      seems to be impossible. In addition, since the term melanocytic dysplasia is not
      precisely defined with regard to all diagnostic methods (clinical morphology,
      dermatoscopy, dermatopathology, molecular biology), there is considerable
      confusion. The question remains if a quite arbitrary classification of
      melanocytic lesions such as dysplastic nevus is useful at all. In daily practice,
      dermatologists should be aware of the fact that each suspicious melanocytic
      lesion could represent an early malignant neoplasia, regardless whether it is
      formally named dysplastic nevus or initial malignant melanoma. We conclude that
      solid dermatological experience plus novel tools of documentation represent the
      key factor to minimize patients' risk.

PMID- 14575037
TI  - Comparison of effects of different anticoagulants and sample handling procedures
      on rat insulin radioimmunoassay.
AB  - 1. The effects of several potential inducers of artifacts on insulin RIA: use of
      anticoagulant (heparin, EDTA) versus clotting , repeated freezing/thawing and the
      presence of added ions (Ca2+, Zn2+) has been studied on a large uniform pooled
      sample of rat blood. 2. Repeated freezing and thawing resulted in a very
      significant loss of RIA insulin. 3. The use of heparin or added lipid
      (Intralipid) to serum samples resulted in lower insulin measurements, whereas low
      protein or EDTA addition resulted in higher values. The effect of EDTA was not a
      consequence of its sequestering of calcium or zinc, as their combined addition
      did not change the EDTA effect. 4. The use of individualized non-specific binding
      for actual insulin estimations did not correct most of the artifacts induced by
      the different treatments studied. 5. As a general conclusion, utmost care must be
      taken to prevent the incidence of these sources of error by referring the data to
      controls, avoiding the use of EDTA as well as taking into account the actual
      composition and handling of the samples when measuring their insulin levels.

PMID- 14575038
TI  - Re: Disease progression and survival of patients with positive lymph nodes after
      radical prostatectomy. Is there a chance of cure?

PMID- 14575039
TI  - The ecophysiological significance of calcium bicarbonate in the urine of
      subterranean rodents: testing a hypothesis.
AB  - 1. A comparative study of calcium and bicarbonate in the urine was carried out on
      the subterranean mole rat Cryptomys hottenttus and the terrestrial vlei rat
      Otomys irroratus. 2. The two species were kept on two different diets; carrots, a
      high calcium diet (41 mg/ 100 kg) or potatoes, a low calcium diet (14 mg/ 100g).
      3. The results show that the urine of the mole rat contained high values of
      calcium bicarbonate on either diet. 4. The urine of the vlei rat showed high
      values of calcium bicarbonate only when kept on the high calcium diet. 5. From
      these results we assume that in subterranean rodents excretion of calcium
      bicarbonate is an adaptive mechanism to unload CO2 without increasing its
      concentration in the hypercapnic environment.

PMID- 14575040
TI  - Energy requirements for gestation and lactation in a delayed implanter, the
      American badger.
AB  - 1. Two adult female badgers were water-deprived and/or fasted during the last one
      half to two-thirds of pregnancy while a third pregnant female received water ad
      libitum and was fed meat and dog food. 2. The litter size, birth weights, post
      partum energy consumption, growth rate, development of homeothermy, tooth
      eruption and date of weaning, as well as other developmental characteristics,
      were not significantly different between cubs born to the fed or fasted mothers.
      3. The energy demands for gestation are apparently small and are accommodated by
      fat reserves during periods of food deprivation. However, the calculated energy
      for lactation is 16 times that of gestation, which is quadruple the expenditure
      for most mammals. 4. As a result of delayed implantation, the length of gestation
      and litter weights of badgers are considerably below those predicted from
      allometric equations. 5. The period of lactation is therefore extremely critical
      to the survival of both the cubs and lactating adults which require heavy fat
      stores and possibly torpor to ensure sufficient energy availability during
      prolonged winter food shortage.

PMID- 14575041
TI  - [Quality assurance of health care: certification has to improve performance and
      quality indicators].

PMID- 14575042
TI  - [A new contract concerning ambulatory surgery has been agreed].

PMID- 14575043
TI  - [Central case management in surgery].
AB  - Up to now, in most surgical departments there has been no central patient
      management coordinating the admission, the diagnostic work-up, and the surgical
      procedures of patients with the resources available in the hospital. In future,
      however, it will be essential for surgical departments to establish such a
      central patient management, not only in view of the importance of patient
      oriented medicine but also considering the planned introduction of diagnosis
      related groups. A central patient management will reduce preoperative and overall
      length of stay through adequate organisation and communication structures. In
      addition, a central patient management will make optimal use of the available
      resources in terms of operation rooms and hospital beds. In this article, we will
      present our basic concept of a central patient management in a surgical
      university department.

PMID- 14575044
TI  - Orr's quantitative trait loci sign test under conditions of trait ascertainment.

PMID- 14575045
TI  - Gametic and zygotic associations.

PMID- 14575046
TI  - Personal reminiscences of the origin and history of cardiopulmonary resuscitation
      (CPR).

PMID- 14575049
TI  - Consumer-directed personal care services for older people in the U.S.

PMID- 14575050
TI  - Clinical pharmacy in Cuba.

PMID- 14575048
TI  - [Drug interactions and the anesthesiologist].
AB  - Modern anesthesiology employs the combined administration of several drugs
      belonging to different pharmacological classes. Additionally, anesthesiologists
      are facing the challenge of polypharmacy regimens utilized by patients considered
      for surgical treatment When drugs are combined, the pharmacological effect may
      considerably differ from the individually expected properties. This may be
      beneficial or potentially lead to adverse drug reactions harming the patient. The
      incidence of drug interaction increases exponentially with the number of drugs
      administered. Depending on the mechanism involved, drug interactions can be
      classified as pharmaceutical, pharmacodynamic, or pharmacokinetic. Although there
      are enormous possibilities for adverse drug reactions nd the complexity is hard
      to identify, prediction of drug interaction is possible. Besides recognizing the
      general risk factors, fundamental knowledge of basic and clinical pharmacology is
      important to prevent serious or fatal drug interactions before they occur.

PMID- 14575051
TI  - Bed covers and dust mites.

PMID- 14575052
TI  - Bed covers and dust mites.

PMID- 14575053
TI  - Bed covers and dust mites.

PMID- 14575054
TI  - Bed covers and dust mites.

PMID- 14575055
TI  - Verification bias in screening for prostate cancer.

PMID- 14575056
TI  - Ventilator withdrawal: procedures and outcomes. Report of a collaboration between
      a critical care division and a palliative care service.
AB  - To describe an institutional procedure for ventilator withdrawal and to analyze
      patient responses to terminal extubation, the medical records of 21 patients who
      underwent withdrawal of mechanical ventilation according to the process followed
      by an interdisciplinary palliative care team were retrospectively reviewed. The
      cohort was a convenience sample of sequentially treated patients in a 1048-bed
      urban university-affiliated medical center. Sixteen of the 21 patients were on
      medical or surgical floors and five patients were in critical care units.
      Patients were assessed for discomfort, such as dyspnea, agitation, or anxiety.
      Sedative and analgesic medications were administered based on clinical
      parameters. Palliative care clinician observations of patient reports,
      tachypnea,use of accessory muscles, and signs of discomfort such as agitation or
      anxiety were recorded for the first 4 hours after extubation. Medication use and
      length of survival were recorded. Fifty-seven percent were symptomatic during the
      extubation process and required administration of either a benzodiazepine or
      opioid medication. The median survival of the 18 patients who died post
      extubation was 0.83 hours (interquartile range 0.5-43.8). Bolus doses of opioid
      or benzodiazepine medications were effective for management of symptoms in about
      two-thirds of patients. One-third of patients required continuous infusions.
      Eighteen patients died following extubation in the medical center, and three of
      these patients were transferred to an inpatient hospice unit. Three patients
      (14%) survived to discharge from the hospital. The procedure followed provides a
      foundation for collaboration between palliative care and critical care services
      to ensure continuity of care across clinical settings/units.

PMID- 14575057
TI  - Effect of nebulized furosemide in terminally ill cancer patients with dyspnea.
AB  - We evaluated the effect of ultrasonically nebulized furosemide (20 mg) on dyspnea
      uncontrollable by standard therapy in patients with terminal cancer. Dyspnea was
      evaluated using the Cancer Dyspnea Scale (CDS) before and 60 min after
      inhalation. Changes in arterial blood gases, hemoglobin oxygen saturation (SpO2),
      heart rate (HR), and respiratory rate (RR) also were evaluated. In 12 of 15
      patients (80%), total dyspnea scores by CDS improved significantly after
      inhalation of furosemide (P = 0.007), especially concerning a reduced sense of
      effort (P = 0.013) and reduced anxiety (P = 0.04). No significant changes were
      observed in the partial pressure of oxygen in arterial blood (PaO2), the partial
      pressure of carbon dioxide in arterial blood (PaCO2), SpO2, HR, or RR. Inhalation
      of nebulized furosemide appears to be effective against dyspnea in terminally ill
      cancer patients.

PMID- 14575058
TI  - Dr. Jamnadas C. Patel.

PMID- 14575059
TI  - Urinary tract infection.

PMID- 14575060
TI  - Enhanced learning: what works in Australia.

PMID- 14575061
TI  - Viruses: origin, evolution and biodiversity. Proceedings of a meeting. Tourtour,
      France, July 24-30, 2000.

PMID- 14575062
TI  - Proceedings of the 8th International Symposium on Neurobehavioral Methods and
      Effects in Occupational and Environmental Health. Brescia, Italy, June 23-26,
      2002.

PMID- 14575063
TI  - A "work sabbath".

PMID- 14575064
TI  - Make clear rules on block scheduling.

PMID- 14575065
TI  - Fixed and frozen flu: the 1918 influenza and lessons for the future.

PMID- 14575066
TI  - Report on avian influenza in the Eastern Hemisphere during 1997-2002.
AB  - Since the Fourth International Symposium on Avian Influenza (AI) there has been
      considerable AI activity in the Eastern Hemisphere. The higher profile of AI
      resulting from the human infections with H5N1 and H9N2 viruses in Hong Kong, in
      1997 and 1999, respectively, resulted in increased reporting and active
      surveillance. There have been three reported incidents of high-pathogenicity (HP)
      AI: H5N2 in northeastern Italy in 1997 (eight outbreaks); H5N1 in Hong Kong in
      1997 recurring in 2001 and 2002; H7N1 in northeasten Italy resulting in 413
      outbreaks in 1999-00. The Italian HPAI outbreaks were preceded by 199 H7N1 low
      pathogenicity (LP) AI outbreaks in 1999, and this virus continued to cause some
      problems after the eradication of HPAI. During the second half of the 1990s
      outbreaks of LPAI due to H9N2 subtype have been reported in Germany, Italy,
      Ireland, South Africa, Hungary, Korea, China, Hong Kong, countries of the Middle
      East, Iran, and Pakistan. The continued presence of virus of this subtype in the
      Middle and Far East may mean it is becoming an established endemic disease in
      those regions. Other more restricted outbreaks in poultry have resulted in the
      isolation of LPAI viruses of H5, H6, H7, and H10 subtypes.

PMID- 14575067
TI  - Avian influenza in the Western Hemisphere including the Pacific Islands and
      Australia.
AB  - Between 1997 and 2001, there was one report of highly pathogenic avian influenza
      (HPAI) in the Western Hemisphere and Pacific Basin. In 1997, in New South Wales,
      Australia, an outbreak caused by avian influenza (AI) virus subtype H7N4 involved
      both chickens and emus. All other reports of infections in poultry and isolations
      from wild bird species in the region pertained to low pathogenicity (LP) AI
      virus. Animal Health Officials in Canada reported isolations of subtypes H1, H6,
      H7, and H10 from domestic poultry and subtypes H3 and H13 from imported and wild
      bird species. In Mexico, the H5N2 LPAI virus, the precursor of the HPAI outbreak
      in 1994-95, was isolated from poultry in each year from 1997 to 2001. Since 1997,
      Mexico has used approximately 708 million doses of a killed H5N2 vaccine and an
      additional 459 million doses of a recombinant fowlpox-H5 vaccine in their H5N2
      control program. In Central America, avian influenza was diagnosed for the first
      time when H5N2 LPAI virus was isolated from chickens in Guatemala and El Salvador
      in 2000 and 2001, respectively. The H5N2 virus was genetically similar to the
      H5N2 virus found in Mexico. Surveillance activities in the United States resulted
      in the detection of AI virus or specific antibodies in domestic poultry from 24
      states. Eleven of the fifteen hemagglutinin (H1, H2, H3, H4, H5, H6, H7, H9, H10,
      H11, and H13) and eight of the nine neuraminidase (N1, N2, N3, N4, N6, N7, N8,
      and N9) subtypes were identified. Two outbreaks of LPAI virus were reported in
      commercial table-egg producing chickens; one caused by H7N2 virus in Pennsylvania
      in 1996-98 and the other caused by H6N2 virus in California in 2000-01. In
      addition, isolations of H5 and H7 LPAI virus were recovered from the live-bird
      markets (LBMs) in the northeast United States.

PMID- 14575068
TI  - An outbreak of highly pathogenic avian influenza in Australia in 1997 caused by
      an H7N4 virus.
AB  - In November of 1997 an outbreak of highly pathogenic avian influenza occurred
      near the town of Tamworth, in northern New South Wales, Australia. The viruses
      isolated from chickens on two commercial chicken farms were identified as H7N4
      viruses, with hemagglutinin cleavage site amino acid sequences of RKRKRG and
      intravenous pathogenicity indices of 2.52 and 2.90, respectively. A virus with an
      identical nucleotide sequence, but with an intravenous pathogenicity index of
      1.30, was also isolated from cloacal swabs collected from asymptomatic emus kept
      on a third property.

PMID- 14575069
TI  - Summary of the 2001-02 Pennsylvania H7N2 low pathogenicity avian influenza
      outbreak in meat type chickens.
AB  - H7N2 low-pathogenicity (LP) avian influenza (AI) virus was isolated from chickens
      submitted to the Pennsylvania Animal Diagnostic Laboratory System on December 4
      and 5, 2001. The cases were from two broiler breeder flocks in central
      Pennsylvania that had clinical signs of an acute, rapidly spreading respiratory
      disease. Seroconversion to AI virus was detected on follow-up sampling.
      Subsequently, H7N2 LPAI virus was isolated in five different broiler flock cases
      submitted between December 14, 2001, and January 3, 2002. Clinical signs and
      lesions in broilers, when present, were compatible with multicausal respiratory
      disease. With the exception of one broiler flock that was processed, birds from
      all of the virus positive flocks were euthanatized in-house within 11 days of the
      original case submission date. Increased surveillance of poultry flocks within 10
      mile radius zones centered at the foci of the positive farms continued until
      March 1, 2002. No additional cases were detected.

PMID- 14575070
TI  - Evaluation of pathogenic potential of avian influenza virus serotype H9N2 in
      chickens.
AB  - Recently seven isolates of avian influenza virus (AIV) serotype H9N2 recovered
      from an outbreak of AI were analyzed on the basis of their biological and
      molecular characteristics. All the isolates belonged to the low-pathogenicity
      group of AIV. To further evaluate their pathogenic potential in association with
      other organisms, an isolate was inoculated experimentally in chickens using
      different routes and subsequently challenged with infectious bronchitis virus,
      Ornithobacterium rhinotracheale or Escherichia coli. The virus isolation and
      seromonitoring data revealed a significant role of Escherichia coli in
      aggravating the clinical condition of the birds earlier infected with AIV (H9N2).
      The AIV-antigen was detected in lung, trachea, kidney, and cloacal bursa among
      the infected birds, using immunofluorescent antibody technique. In another
      experiment, chickens that were immunosuppressed chemically showed high mortality
      when challenged with AIV H9N2. The results indicated that this low pathogenicity
      AIV (H9N2) isolate could produce severe infection depending on the type of
      secondary opportunistic pathogens present under field conditions. This may
      explain the severity of infection with the present H9N2 outbreak in the field. A
      prolonged antibacterial therapy in flocks infected with AIV H9N2 and use of oil
      based vaccine at an early age in new flocks has helped to control this infection
      and the disease.

PMID- 14575071
TI  - A review of the 1996-98 nonpathogenic H7N2 avian influenza outbreak in
      Pennsylvania.
AB  - The nonpathogenic avian influenza (AI) outbreak in Pennsylvania began in December
      1996 when there was a trace back from a New York live bird market to a dealer's
      flock. A total of 18 commercial layer flocks, two commercial layer pullet flocks,
      and a commercial meat turkey flock were diagnosed with nonpathogenic AI (H7N2)
      viral infection with an economic loss estimated at between 3 and 4 million
      dollars. Clinical histories of flocks infected with the disease included
      respiratory disease, elevated morbidity and mortality throughout the house, egg
      production drops, depression, and lethargy. A unique gross lesion in the
      commercial layers was a severe, transmural oviduct edema with white to gray
      flocculent purulent material in the lumen. Layer flocks on two separate premises
      were quarantined but permitted to remain in the facilities until cessation of
      virus shed was determined through virus isolation. Several months later, clinical
      AI appeared again in these flocks. It is not known whether the recurrence of
      disease in these cases is due to persistence of the organism in the birds or the
      environment. In addition to serologic testing and virologic testing by chicken
      embryo inoculation, an antigen capture enzyme immunoassay was evaluated as a
      diagnostic tool for AI. Research projects related to disinfection, burial pits,
      and geographical system technology were developed because of questions raised
      concerning transmission, diagnosis, and control of nonpathogenic AI (H7N2).

PMID- 14575072
TI  - Avian influenza (H9N2) outbreak in Iran.
AB  - An epidemic of avian influenza (AI) (H9N2) occurred in broiler chicken farms in
      Iran during 1998-01. Mortality between 20% and 60% was commonly observed on the
      affected farms. Mixed infections of the influenza virus with other respiratory
      pathogens, particularly infectious bronchitis virus and Mycoplasma gallisepticum,
      were thought to be responsible for such high mortality, which resulted in great
      economic losses. Clinical signs included swelling of the periorbital tissues and
      sinuses, typical respiratory discharge, and severe respiratory distress. Gross
      lesions included extensive hyperemia of the respiratory system followed by
      exudation and cast formation in the tracheal biforcation extending into the
      secondary bronchi. Light microscopy lesions were characterized by severe
      necrotizing tracheatis. Serological examination using H9N2 AI viral antigen
      produced inconsistent results. Ultrastructural findings showed typical viral
      replication through budding processes on cell membranes of the tracheal
      epithelium.

PMID- 14575073
TI  - Avian influenza in Hong Kong 1997-2002.
AB  - In 1997, a high-pathogenicity H5N1 avian influenza virus caused serious disease
      in both man and poultry in Hong Kong, China. Eighteen human cases of disease were
      recorded, six of which were fatal. This unique virus was eliminated through total
      depopulation of all poultry markets and chicken farms in December 1997. Other
      outbreaks of high-pathogenicity avian influenza (HPAI) caused by H5N1 viruses
      occurred in poultry in 2001 and 2002. These H5N1 viruses isolated had different
      internal gene constellations to those isolated in 1997. No new cases of infection
      or disease in man due to these or other H5N1 viruses have been reported. This
      paper provides an overview and chronology of the events in Hong Kong relating to
      avian influenza, covering the period from March 1997 to March 2002.

PMID- 14575074
TI  - Avian influenza in Italy 1997-2001.
AB  - From 1997 to 2001, Italy has been affected by two epidemics of high-pathogenicity
      avian influenza. The first epidemic was caused by a virus of the H5N2 subtype and
      was limited to eight premises in backyard and semi-intensive flocks. The prompt
      identification of the disease was followed by the implementation of European
      Union (EU) directive 92/40/EEC and resulted in the eradication of infection
      without serious consequences to the poultry industry. The 1999-00 epidemic was
      caused by a virus of the H7N1 subtype that originated from the mutation of a low
      pathogenic virus and resulted instead in a devastating epidemic that affected
      industrially reared poultry, culminating in the infection of 413 flocks. The
      description of the epidemics and the result of the control policies are reported.

PMID- 14575075
TI  - Clinical, gross, and microscopic findings in different avian species naturally
      infected during the H7N1 low- and high-pathogenicity avian influenza epidemics in
      Italy during 1999 and 2000.
AB  - From the end of March to the beginning of December 1999, an epidemic of low
      pathogenicity avian influenza (LPAI), caused by a H7N1 type A influenza virus,
      affected the intensively reared poultry population of Northeastern Italy. A total
      of 199 flocks were diagnosed with influenza infection. The highest number
      affected flocks were in meat turkeys (164), with only a limited number of turkey
      breeder, chicken (breeders, broilers, and table egg layers), and guinea fowl
      flocks infected. Following the circulation of the LPAI virus in a susceptible
      population for several months, a high-pathogenicity avian influenza (HPAI) virus
      emerged. Over 13 million birds on 413 different premises were affected by the
      HPAI virus, including turkey, chicken, guinea fowl, pheasant, Japanese quail,
      ostrich, and waterfowl flocks. In the present paper we report on the clinical,
      gross, histopathological, and immunohistochemical investigations performed on
      different avian species naturally infected by the LPAI virus and the HPAI virus.

PMID- 14575076
TI  - The quest of influenza A viruses for new hosts.
AB  - There is increasing evidence that stable lineages of influenza viruses are being
      established in chickens. H9N2 viruses are established in chickens in Eurasia, and
      there are increasing reports of H3N2, H6N1, and H6N2 influenza viruses in
      chickens both in Asia and North America. Surveillance in a live poultry market in
      Nanchang, South Central China, reveals that influenza viruses were isolated form
      1% of fecal samples taken from healthy poultry over the course of 16 months. The
      highest isolation rates were from chickens (1.3%) and ducks (1.2%), followed by
      quail (0.8%), then pigeon (0.5%). H3N6, H9N2, H2N9, and H4N6 viruses were
      isolated from multiple samples, while single isolates of H1N1, H3N2, and H3N3
      viruses were made. Representatives of each virus subtype were experimentally
      inoculated into both quail and chickens. All the viruses replicated in the
      trachea of quail, but efficient replication in chickens was confined to 25% of
      the tested isolates. In quail, these viruses were shed primarily by the aerosol
      route, raising the possibility that quail may be the "route modulator" that
      changes the route of transmission of influenza viruses from fecal-oral to aerosol
      transmission. Thus, quail may play an important role in the natural history of
      influenza viruses. The pros and cons of the use of inactivated and recombinant
      fowl pox-influenza vaccines to control the spread of avian influenza are also
      evaluated.

PMID- 14575077
TI  - Influenza A virus surveillance in wild birds in Northern Europe in 1999 and 2000.
AB  - Using reverse transcription/polymerase chain reaction (RT-PCR), we have screened
      more than 8500 wild birds in Northern Europe in 1999 and 2000 for the presence of
      influenza A virus. Although our primary focus was on ducks, geese, and
      shorebirds, we have also tested thousands of samples from other bird species.
      Approximately 1% of our samples were positive for influenza A virus by RT-PCR,
      and from half of these we were able to isolate influenza A virus in embryonated
      chicken eggs. A wide variety of isolates was obtained representing hemagglutinin
      (HA) subtypes 1 through 7, 10, 11, 13, an unidentifiable HA, and neuraminidase
      (NA) subtypes 1 through 8.

PMID- 14575078
TI  - Circulation of influenza viruses in wild waterfowl wintering in Italy during the
      1993-99 period: evidence of virus shedding and seroconversion in wild ducks.
AB  - The mechanisms of perpetuation of influenza A viruses in aquatic birds, their
      main reservoir in nature, have not yet been completely clarified. One hypothesis
      is that they continue to circulate in waterfowl throughout the year, even though
      virus isolations during the winter months are rare. We analyzed influenza virus
      circulation in wild ducks in Italy during six winter seasons (1993-99), using
      virus isolations and serological analyses. It was apparent that influenza A
      viruses were constantly circulating in wild birds during all the seasons
      considered. Moreover, seroconversion rates (obtained from ducks recaptured during
      the same season) suggest a frequency of influenza infections higher than expected
      on the basis of the virus isolation rates.

PMID- 14575079
TI  - Avian influenza viruses in Minnesota ducks during 1998-2000.
AB  - Although wild ducks are known to be a major reservoir for avian influenza viruses
      (AIV), there are few recent published reports of surveillance directed at this
      group. Predominant AIV hemagglutinin (HA) subtypes reported in previous studies
      of ducks in North America include H3, H4, and H6, with the H5, H7, and H9
      subtypes not well represented in these host populations. The objective of this
      study was to determine whether these subtype patterns have persisted. Each
      September from 1998 to 2000, cloacal swabs were collected from wild ducks banded
      in Roseau and Marshall counties, MN. Mallards (Anas platyrhynchos) were sampled
      all years, and northern pintails (A. acuta) were sampled only in 1999. Influenza
      viruses were isolated from 11%, 14%, and 8% of birds during 1998, 1999, and 2000,
      respectively. Prevalence, as expected, was highest in juveniles, ranging from 11%
      to 23% in mallards. Viruses representative of the HA subtypes 2, 3, 4, 5, 6, 7,
      9, 10, 11, and 12 were isolated. Viruses in the H5, H7, and H9 subtypes, which
      are associated with high-pathogenicity influenza in poultry or recent infections
      in humans, were not uncommon, and each of these subtypes was isolated in 2 out of
      the 3 years of surveillance.

PMID- 14575080
TI  - Low-pathogenicity avian influenza virus (H6N2) in chickens in California, 2000
      02.
AB  - During 2000, 2001, and January 2002, avian influenza virus was isolated from
      chickens from 12 different locations in California. All the isolates were typed
      as H6N2 and determined to be of low pathogenicity for chickens. Nine of the
      isolates came from commercial layer flocks; one from a backyard flock; one from a
      mixed age flock, where ducks and squabs were also present; and one from a primary
      broiler breeder. Although a drop in egg production and increased mortality were
      among the disease signs reported in the layer flocks, the pathological changes
      observed in the early cases were primarily associated with mild respiratory
      infections. It was not until August 2001 that yolk peritonitis was observed; this
      has been a feature of all the remaining cases through 2001 and 2002. All the
      isolates clustered as a unique group separate from other influenza viruses based
      upon sequence data of the H6, neuraminidase (N2), and matrix (MA) genes,
      indicating a common ancestor for these three gene segments. However, sequencing
      of the nonstructural (NS) gene indicates introductions from two separate origins.
      With the first isolate CK/CA/431/00 as the index case, the N2, MA, and NS genes
      are more closely related to North American isolates, as is the NP gene of
      CK/CA/650/00. In contrast, the H6 gene is more closely related to a Eurasian
      influenza isolate. Comparison of amino acid sequences of the N2 and MA genes of
      these isolates with available type A influenza viruses identified two unique
      changes in the MA gene and nine in the N2 gene, as well as four progressive
      changes. These results are discussed in relation to available clinical and
      epidemiological data.

PMID- 14575081
TI  - Reverse genetics for the control of avian influenza.
AB  - Avian influenza viruses are major contributors to viral disease in poultry as
      well as humans. Outbreaks of high-pathogenicity avian influenza viruses cause
      high mortality in poultry, resulting in significant economic losses. The
      potential of avian influenza viruses to reassort with human stains resulted in
      global pandemics in 1957 and 1968, while the introduction of an entirely avian
      virus into humans claimed several lives in Hong Kong in 1997. Despite
      considerable research, the mechanisms that determine the pathogenic potential of
      a virus or its ability to cross the species barrier are poorly understood.
      Reverse genetics methods, i.e., methods that allow the generation of an influenza
      virus entirely from cloned cDNAs, have provided us with one means to address
      these issues. In addition, reverse genetics is an excellent tool for vaccine
      production and development. This technology should increase our preparedness for
      future influenza virus outbreaks.

PMID- 14575082
TI  - Update on molecular epidemiology of H1, H5, and H7 influenza virus infections in
      poultry in North America.
AB  - Avian influenza is endemic in wild birds in North America, and the virus
      routinely has been transmitted from this reservoir to poultry. Influenza, once
      introduced into poultry, can become endemic within the poultry population. It may
      be successfully eradicated by human intervention, or the virus may fail to
      successfully spread on its own. In the last 5 yr, influenza virus has been
      isolated from poultry in the United States on numerous occasions, and, with the
      use of molecular epidemiology, the relationships of these different viruses can
      be determined. There are 15 different hemagglutinin subtypes of avian influenza
      viruses, but infections with virus of H5 and H7 subtypes are of the most concern
      because of the potential for these viruses to mutate to the highly pathogenic
      form of the virus. Most of the influenza isolations in the United States have
      been associated with the live-bird markets (LBMs) in the Northeast. This has
      included primarily H7N2 influenza viruses, but also H7N3, H5N2, and other
      subtypes. Most of the H7N2 viruses were part of a single lineage that was first
      observed in 1994, but new introductions of H7N2 and H7N3 were also observed. The
      predominant H7N2 LBM lineage of virus spread to large commercial poultry
      operations on at least three occasions since 1997, with the largest outbreak
      occurring in Virginia in 2002. The H5N2 viruses in the LBMs included viruses from
      domestic ducks, gamebirds, and environmental samples. Some H5N2 viruses isolated
      in different years and in different locations had a high degree of sequence
      relatedness, although the reservoir source, if it is endemic, has not been
      identified. Finally, an H1N2 virus, associated with a drop in egg production, was
      isolated from turkeys in Missouri in 1999. This virus was a complex reassortant
      with swine, human, and avian influenza genes that was similar to recent swine
      isolates from the Midwest. Additional serologic evidence suggests that flocks in
      other states were infected with a H1N2 virus.

PMID- 14575083
TI  - Molecular and biological characteristics of H5 and H7 avian influenza viruses in
      live-bird markets of the northeastern United States, 1994-2001.
AB  - Surveillance for H5 and H7 subtypes of avian influenza virus (AIV) in the live
      bird markets (LBMs) of the northeastern United States has been in effect since
      1986 when the markets were first recognized as a potential reservoir for AIV.
      Long-term maintenance of AIV in the LBM system has been documented. However,
      little is known about the influence of successive cycles of replication in
      unnatural avian hosts (gallinaceous birds) on the genetics of the virus,
      especially in the region of the hemagglutinin (HA) gene that can influence
      pathogenicity. Isolation of low-pathogenicity H5 AIVs from the LBMs has been
      sporadic; however, in 1994 a low-pathogenicity H7N2 virus was isolated that has
      persisted in the LBMs for more than 7 yr. Efforts to eliminate the H7 virus from
      the markets have been unsuccessful. During the 7-yr period, several molecular
      changes have occurred at the hemagglutinin cleavage site of the H7 virus. These
      changes include substitutions of proline for threonine and lysine for asparagine,
      respectively, at the -2 and -5 positions of the HA1 protein. In addition, there
      has been a 24 nucleotide base-pair deletion in the receptor binding region of the
      HA1. The accumulation of an additional basic amino acid at the cleavage site is a
      cause for concern to regulatory authorities, and, therefore, efforts to eliminate
      the virus from the LBM system have been intensified.

PMID- 14575084
TI  - Multiple genotypes of nonpathogenic H6N2 influenza viruses isolated from chickens
      in California.
AB  - From February 2000 through September 2001, a limited number of H6N2 influenza
      viruses were isolated from chickens in California. This report describes the
      genetic characterization of nine of these H6N2 viruses. All of the viruses
      analyzed had phylogenetically similar hemagglutinin (HA) and neuraminidase
      molecules that suggested the viruses shared a recent common ancestor. The
      analysis of the HA sequence of these viruses with all available H6 viruses from
      different hosts and locations showed that these genes do not separate into well
      defined North American and Eurasian lineages. The neuraminidase genes of the
      California viruses contain an 18 amino acid deletion, a possible adaptation to
      growth in chickens. Analysis of the remaining gene segments of the California
      viruses revealed that three distinct genotypes of H6N2 viruses were present.

PMID- 14575085
TI  - Reassortants of H5N1 influenza viruses recently isolated from aquatic poultry in
      Hong Kong SAR.
AB  - The H5N1 virus (H5N1/97) that caused the bird flu incident in Hong Kong in 1997
      has not been isolated since the poultry slaughter in late 1997. But the donor of
      its H5 hemagglutinin gene, Goose/Guangdong/1/96-like (Gs/Gd/96-like) virus,
      established a distinct lineage and continued to circulate in geese in the area.
      In 2000, a virus from the Goose/Guangdong/1/96 lineage was isolated for the first
      time from domestic ducks. Subsequently, it has undergone reassortment, and these
      novel reassortants now appear to have replaced Gs/Gd/96-like viruses from its
      reservoir in geese and from ducks. The internal gene constellation is also
      different from H5N1/97, but these variants have the potential for further
      reassortment events that may allow the interspecies transmission of the virus.

PMID- 14575086
TI  - The impact of avian influenza viruses on public health.
AB  - In the late 1990s, H5N1 and H9N2 avian influenza viruses caused respiratory
      infections in humans in Hong Kong. Exposure to domestic poultry in live-bird
      markets was significantly associated with human H5N1 disease. Seroepidemiologic
      studies conducted among contacts of H5N1-infected persons determined that human
      to-human transmission of the avian H5N1 viruses occurred but was rare. The
      relatively high rates of H5 and H9 antibody seroprevalence among Hong Kong
      poultry workers in 1997 highlight the potential for avian viruses to transmit to
      humans, particularly those with occupational exposure. Such transmission
      increases the likelihood of reassortment between a currently circulating human
      virus and an avian virus and thus the creation of a strain with pandemic
      potential.

PMID- 14575087
TI  - Relationship of pre-1918 avian influenza HA and NP sequences to subsequent avian
      influenza strains.
AB  - Wild waterfowl that were captured between 1915 and 1919 and preserved in 70%
      ethyl alcohol were tested for influenza A virus RNA. Most of the HA1 domain of
      the hemagglutinin (HA) gene segment was sequenced from one bird, captured in
      1917, that was infected with a virus of the same HA subtype as the 1918 human
      pandemic virus. The 1917 HA sequence is closely related to modern avian HA
      sequences, suggesting little drift in avian sequences in 80 years and that the
      1918 pandemic virus probably did not acquire its hemagglutinin directly from a
      bird. A 151-bp fragment of the nucleoprotein gene segment was sequenced from two
      pre-1918 birds and compared to avian and mammalian influenza strains. The 1917
      avian NP sequences are also closely related to modern avian sequences and
      distinct from the mammalian clade in which the 1918 NP sequence is found.

PMID- 14575088
TI  - Safety evaluation in chickens of candidate human vaccines against potential
      pandemic strains of influenza.
AB  - Two candidate formalin-inactivated vaccines, made from high-growth reassortant
      viruses with the HA and NA genes from avian viruses in a background of genes
      derived from A/Puerto Rico/8/34 (PR8), were prepared against H5N1 and H9N2
      subtypes (designated as H5N1/PR8 and H9N2/PR8, respectively). These viruses bear
      the genotypes, antigenicity, and attenuation in mouse models that are desirable
      in candidate vaccines. The pathogenicity of the newly generated avian-human
      reassortant vaccine viruses was also evaluated in chickens. Neither H5N1/PR8 nor
      H9N2/PR8 were highly pathogenic for chickens. No clinical signs, gross legions,
      or histological lesions were observed in chickens that were administered H5N1/PR8
      either intranasally (i.n.) or intravenously (i.v.), and virus was not detected in
      oropharyngeal or cloacal swabs. When H9N2/PR8 was administered i.n., no clinical
      signs, gross lesions, or histological lesions were observed and no virus was
      detected in cloacal swabs. However, virus was isolated at low titer from
      oropharyngeal swabs of all eight chickens. Although no clinical signs were
      observed when H9N2/PR8 was administered i.v., mild tracheitis was seen in one of
      two chickens. Moderate amounts of antigen were observed in tracheal respiratory
      epithelium, and low titers of virus were recovered from oropharyngeal and cloacal
      swabs of some chickens. In summary, both reassortant vaccine viruses replicated
      poorly in chickens. These studies suggest that these candidate vaccine viruses
      carry a low risk of transmission to chickens.

PMID- 14575089
TI  - A primate model to study the pathogenesis of influenza A (H5N1) virus infection.
AB  - Cynomolgus macaques (Macaca fascicularis) infected with influenza virus
      A/HongKong/156/97 (H5N1) developed acute respiratory distress syndrome (ARDS)
      with fever. Reverse transcriptase/polymerase chain reaction (RT/PCR) and virus
      isolation showed that the respiratory tract is the major target of the virus. The
      main lesion observed upon necropsy, performed 4 or 7 days postinfection, was a
      necrotizing bronchointerstitial pneumonia, similar to that found in primary
      influenza pneumonia in human beings. By immunohistochemistry, influenza virus
      antigen proved to be limited to pulmonary tissue and tonsils. The data indicate
      that ARDS and multiple organ dysfunction syndrome (MODS), observed in both humans
      and monkeys infected with this virus, are caused by diffuse alveolar damage from
      virus replication in the lungs alone.

PMID- 14575090
TI  - The WHO Global Influenza Program and its Animal Influenza Network.
AB  - The World Health Organization (WHO) Global Influenza Program makes annual
      recommendations on influenza vaccine formulation and related activities. This
      results in 230 million annual doses of vaccine produced for human use. The
      success of this program is based on the collection and genetic and antigenic
      analyses of influenza viruses collected by the WHO Global Influenza Surveillance
      Program. New programs focus on pandemic preparedness and include development and
      distribution of testing reagents for emerging or potentially emerging human
      influenza viruses. WHO Animal Influenza Network focuses on aspects of ecology and
      molecular biology of animal influenza viruses in the context of human health.

PMID- 14575091
TI  - Transmission dynamics of low- and high-pathogenicity A/Chicken/Pennsylvania/83
      avian influenza viruses.
AB  - High-pathogenicity avian influenza (HPAI) viruses emerged from low-pathogenicity
      avian influenza (LPAI) viruses in Pennsylvania (1983-84), Mexico (1994-95), and
      Italy (1999-2000). Here we focus on the question of why the HPAI virus supersedes
      the LPAI virus, once it has appeared during the epidemic. To study this, we used
      an experimental model in chickens that enabled us to estimate the reproduction
      ratio (R0). Using this model, we determined the R0 of the
      A/Chicken/Pennsylvania/21525/83 (LPAI) and of the A/Chicken/Pennsylvania/1370/83
      (HPAI). Comparing the R0 of both viruses, we concluded that the R0 of the HPAI
      virus is significantly higher than the R0 of the LPAI.

PMID- 14575092
TI  - Additional glycosylation at the receptor binding site of the hemagglutinin (HA)
      for H5 and H7 viruses may be an adaptation to poultry hosts, but does it
      influence pathogenicity?
AB  - Sequence analysis of the hemagglutinin (HA) gene of H5 and H7 viruses was used to
      determine phylogenetic relationships between high-pathogenicity avian influenza
      (HPAI) and low-pathogenicity avian influenza (LPAI) viruses from avian influenza
      (AI) outbreaks in Norfolk in 1979 and 1991 and Italy in 1999-2000. A common
      feature within these groups of viruses was the acquisition of additional
      glycosylation sites near the receptor binding site of the HA. Passage of H5
      viruses through 14-day-old embryonated fowls' eggs readily selected viruses with
      additional glycosylation of HA1. Although additional glycosylation may not
      correlate with increased pathogenicity for fowl, it may predispose viruses to
      become highly pathogenic.

PMID- 14575093
TI  - Evaluation of a high-pathogenicity H5N1 avian influenza A virus isolated from
      duck meat.
AB  - The introduction of an influenza A virus possessing a novel hemagglutinin (HA)
      into an immunologically naive human population has the potential to cause severe
      disease and death. Such was the case in 1997 in Hong Kong, where H5N1 influenza
      was transmitted to humans from infected poultry. Because H5N1 viruses are still
      isolated from domestic poultry in southern China, there needs to be continued
      surveillance of poultry and characterization of virus subtypes and variants. This
      study provides molecular characterization and evaluation of pathogenesis of a
      recent H5N1 virus isolated from duck meat that had been imported to South Korea
      from China. The HA gene of A/Duck/Anyang/AVL-1/01 (H5N1) isolate was found to be
      closely related to the Hong Kong/97 H5N1 viruses. This virus also contained
      multiple basic amino acids adjacent to the cleavage site between HA1 and HA2,
      characteristic of high-pathogenicity avian influenza viruses (HPAI). The
      pathogenesis of this virus was characterized in chickens, ducks, and mice. The
      DK/Anyang/AVL-1/01 isolate replicated well in all species and resulted in 100%
      and 22% lethality for chickens and mice, respectively. No clinical signs of
      disease were observed in DK/Anyang/AVL-1/01-inoculated ducks, but high titers of
      infectious virus could be detected in multiple tissues and oropharyngeal swabs.
      The presence of an H5N1 influenza virus in ducks bearing a HA gene that is highly
      similar to those of the pathogenic 1997 human/poultry H5N1 viruses raises the
      possibility of reintroduction of HPAI to chickens and humans.

PMID- 14575094
TI  - Comparative susceptibility of selected avian and mammalian species to a Hong Kong
      origin H5N1 high-pathogenicity avian influenza virus.
AB  - Seventeen avian species and two mammalian species were intranasally inoculated
      with the zoonotic A/chicken/Hong Kong/220/97 (chicken/HK) (H5N1) avian influenza
      (AI) virus in order to ascertain a relative range of susceptible hosts and the
      pathobiology of the resultant disease. A direct association was demonstrated
      between viral replication and the severity of disease, with four general
      gradations being observed among these species. These gradations included the
      following: 1) widespread dissemination with rapid and high mortality, 2)
      neurological disease relative to viral neurotropism, 3) asymptomatic infection or
      only mild transient depression associated with minor viral replication, and 4)
      absence of disease relative to minimal to no viral replication. This
      investigation not only demonstrates that the chicken/HK virus could infect
      multiple avian species, but also that the virulence of the chicken/HK virus
      varied significantly among avian species, including those species that are
      members of the same order.

PMID- 14575095
TI  - Examining the cellular pathways involved in influenza virus induced apoptosis.
AB  - Apoptosis is essential in many physiological processes including wound healing
      and development of the immune response. Apoptosis also plays an important role in
      the pathogenesis of many infectious diseases including those caused by viruses.
      Influenza viruses induce apoptosis in cells that are permissive for viral
      replication and cells that do not support viral replication. The cellular
      pathways involved in influenza virus induced apoptosis are currently ill defined.
      Previous studies suggest that influenza virus infection increased the expression
      of the Fas antigen in HeLa cells, and that Fas antigen is partially involved in
      apoptosis. In these studies we examined the cellular pathways involved in avian
      influenza virus induced apoptosis in two cell lines that support productive viral
      replication: Madin-Darby canine kidney cells (MDCK) and mink lung epithelial
      (Mv1Lu) cells.

PMID- 14575096
TI  - International standards for the control of avian influenza.
AB  - The Office International des Epizooties (OIE) has developed international
      standards to reduce the risk of the spread of high-pathogenicity avian influenza
      though international trade. These standards include providing a definition of
      high-pathogenicity avian influenza (HPAI), procedures for prompt reporting of
      HPAI outbreaks, requirements that must be met for a country or zone to be defined
      as free of HPAI, requirements that should be met to import live birds and avian
      products into a HPAI-free country or zone, and the general provisions that
      countries should meet to reduce the risk of spread of HPAI through trade. The
      goal of these standards is to facilitate trade while minimizing the risk of the
      introduction of HPAI.

PMID- 14575097
TI  - Should we change the definition of avian influenza for eradication purposes?
AB  - The current definitions of high-pathogenicity avian influenza (HPAI), formulated
      over 10 years ago, were aimed at including viruses that were overtly virulent in
      in vivo tests and those that had the potential to become virulent. At that time
      the only virus known to have mutated to virulence was the one responsible for the
      1983-84 Pennsylvania epizootic. The mechanism involved has not been seen in other
      viruses, but the definition set a precedent for statutory control of potentially
      pathogenic as well as overtly virulent viruses. The accumulating evidence is that
      HPAI viruses arise from low-pathogenicity avian influenza (LPAI) H5 or H7 viruses
      infecting chickens and turkeys after spread from free-living birds. At present it
      can only be assumed that all H5 and H7 viruses have this potential and mutation
      to virulence is a random event. Therefore, the longer the presence and greater
      the spread in poultry the more likely it is that HPAI virus will emerge. The
      outbreaks in Pennsylvania, Mexico, and Italy are demonstrations of the
      consequences of failing to control the spread of LPAI viruses of H5 and H7
      subtypes. It therefore seems desirable to control LPAI viruses of H5 and H7
      subtype in poultry to limit the probability of a mutation to HPAI occurring. This
      in turn may require redefining statutory AI. There appear to be three options: 1)
      retain the current definition with a recommendation that countries impose
      restrictions to limit the spread of LPAI of H5 and H7 subtypes; 2) define
      statutory AI as an infection of birds/poultry with any AI virus of H5 or H7
      subtype; 3) define statutory AI as any infection with AI virus of H5 or H7
      subtype, but modify the control measures imposed for different categories of
      virus and/or different types of host.

PMID- 14575098
TI  - USDA options for regulatory changes to enhance the prevention and control of
      avian influenza.
AB  - During the past decade, several examples of the ability of H5 and H7 low
      pathogenicity avian influenza (LPAI) viruses to mutate to high-pathogenicity (HP)
      viruses have been documented worldwide. During this time, the introduction and
      persistence of an H7N2 LPAI virus in the northeast live-bird marketing system in
      the United States has raised concern on how to prevent the possibility of such a
      mutation occurring in this country. The United States has periodically
      experienced trade restrictions based on the occasional introduction of H5 and H7
      LPAI viruses into commercial poultry and based on AI-related changes in the
      import requirements for poultry and poultry products of several of our trading
      partners. Consequently, the U.S. Department of Agriculture (USDA) is exploring
      options for how our regulatory response to H5 and H7 LPAI viruses might be
      revised to better protect our domestic poultry flocks from HPAI and to ensure
      that any interruptions in trade are scientifically supportable. The options under
      consideration include mandatory and voluntary measures to improve the
      surveillance for and control of H5 and H7 LPAI virus infections.

PMID- 14575099
TI  - The impact of new epidemiological information on a risk analysis for the
      introduction of avian influenza viruses in imported poultry meat.
AB  - New Zealand has never experienced an outbreak of avian influenza, and the
      Ministry of Agriculture and Forestry has long been wary of the possibility of
      introducing high-pathogenicity avian influenza (HPAI) viruses in imported goods.
      Besides the potential threat posed to poultry, there are concerns that introduced
      viruses might have negative effects on already endangered native avian species.
      Under the framework of the World Trade Organization, the sanitary and
      phytosanitary (SPS) agreement requires member countries to base their sanitary
      measures for imported animal products on the Office International des Epizooties
      (OIE) standard or on a scientific assessment of risk. This paper presents the New
      Zealand experience with assessing the risk of avian influenza viruses in imported
      chicken meat and considers how the assessment of risk has changed in recent years
      as a result of the advances in understanding of the disease. The currently
      accepted view that low-pathogenicity avian influenza (LPAI) viruses are
      widespread and that they mutate to virulence after introduction into poultry has
      important implications concerning the appropriate definition for avian influenza
      viruses of regulatory concern and has possible implications concerning the
      significance of viruses present in this country.

PMID- 14575101
TI  - An update on avian influenza in Mexico.
AB  - The avian influenza high-pathogenicity virus was eradicated in poultry of Mexico
      in a relatively short period by the use of inactivated emulsified vaccine,
      enforcing biosecurity, and controlling movement of poultry and poultry products.
      Mexico maintains a permanent and reliable monitoring program for AI. H5N2 is the
      only avian influenza subtype identified. It is possible to control and eradicate
      the avian influenza low-pathogenicity virus mainly by controlled depopulation of
      positive poultry, reinforcing biosecurity, and the use of vaccines.

PMID- 14575100
TI  - Epidemiologic and surveillance studies on avian influenza in live-bird markets in
      New York and New Jersey, 2001.
AB  - In 2001, all 109 retail live-bird markets (LBMs) in New York and New Jersey were
      surveyed for the presence of avian influenza virus (AIV) by a real time reverse
      transcriptase/polymer chain reaction assay (RRT/PCR) and results compared to
      virus isolation (VI) in embryonating chicken eggs. The RRT/PCR had a 91.9%
      sensitivity and 97.9% specificity in detecting presence of AIV at the market
      level. However, the sensitivity at the sample level is 65.87%. The RRT/PCR is a
      reliable method to identify AIV at the market level. In addition, a cross
      sectional epidemiologic study of the LBMs showed that, during the past 12 months,
      markets that were open 7 days per week and those that also sold rabbits had the
      highest risk for being positive for AIV. Markets that were closed one or more
      days per week and those that performed daily cleaning and disinfecting had the
      lowest risk for being AIV positive.

PMID- 14575102
TI  - Low-pathogenicity avian influenza (LPAI) in Italy (2000-01): epidemiology and
      control.
AB  - In 1999-2000, Italy was affected by the most severe avian influenza (AI) epidemic
      that has ever occurred in Europe. The epidemic was caused by a type A influenza
      virus of the H7N1 subtype, which originated from the mutation of a low
      pathogenicity (LP) AI virus of the same subtype. From August to November 2000, 4
      months after the eradication of the highly pathogenic (HP) AI virus, the LPAI
      strain re-emerged and infected 55 poultry farms mainly located in the southern
      area of Verona province (Veneto region). To supplement disease control measures
      already in force, an emergency vaccination program against the disease was
      implemented in the area. Vaccination was carried out using an inactivated
      heterologous vaccine (A/chicken/Pakistan/1995-H7N3). In order to establish
      whether LPAI infection was circulating in the area, regular serological testing
      of sentinel birds in vaccinated flocks and a discriminatory test able to
      distinguish the different types of antineuraminidase antibodies (anti-N1 and anti
      N3) were performed. Shortly after the beginning of the vaccination campaign
      (December 2000 to March 2001), the H7N1 LPAI virus emerged again, infecting 23
      farms. Among these, only one vaccinated flock was affected, and infection did not
      spread further to other vaccinated farms. The data reported in the present paper
      indicate that the combination of biosecurity measures, official control, and
      vaccination can be considered successful for the control of LPAI infections in
      densely populated poultry areas.

PMID- 14575103
TI  - The use of Geographic Information System (GIS) in the frame of the contingency
      plan implemented during the 1999-2001 avian influenza (AI) epidemic in Italy.
AB  - A Geographic Information System (GIS) is a very powerful and flexible software
      tool for effective management of spatially referenced data (e.g., geodata).
      Coupling database and GIS technology provides the tools for a detailed analysis
      of spatial patterns and distributions in veterinary applications. A specific
      veterinary GIS (VetGIS) toolbox was developed to perform the calculation of
      indices such as Lorenz curve, GINI index, and a kernel-based animal density
      estimation. This software was employed for the analysis and management of avian
      influenza in Italy during the 1999-2000 epidemic.

PMID- 14575104
TI  - Survival of avian influenza virus H7N2 in SPF chickens and their environments.
AB  - The survival or clearance of the avian influenza virus (AIV) of subtype H7N2 in
      its chicken host was evaluated using experimentally infected specific pathogen
      free (SPF) chickens of different age groups. Birds of different ages were
      successfully infected with infectious doses ranging between 10(4.7) and 10(5.7)
      ELD50 per bird. In infected birds, the infective virus was undetectable usually
      by the third week following exposure. The infectivity or inactivation time of the
      H7N2 AIV in various environmental conditions was studied using chicken manure,
      heat, ethanol, pH, and disinfectants. The H7N2 AIV was effectively inactivated by
      field chicken manure in less than a week at an ambient temperature of 15-20
      degrees C. At a pH 2, heating at 56 degrees C, and exposure to 70% ethanol or a
      specific disinfectant, the AIV infectivity was destroyed in less than 30 min.

PMID- 14575105
TI  - Epidemiology, production losses, and control measures associated with an outbreak
      of avian influenza subtype H7N2 in Pennsylvania (1996-98).
AB  - An outbreak of H7N2 low-pathogenicity (LP) avian influenza (AI) occurred in a two
      county area in Pennsylvania from December of 1996 through April of 1998. The
      outbreak resulted in infection of 2,623,116 commercial birds on 25 premises
      encompassing 47 flocks. Twenty-one (one premise with infection twice) of the
      twenty-five infected premises housed egg-laying chickens and one premise each had
      turkeys, layer pullets, quail, and a mixed backyard dealer flock. Despite dose
      proximity of infected flocks to commercial broiler flocks, no infected broilers
      were identified. Experimentally, when market age broilers were placed on an
      influenza-infected premise they seroconverted and developed oviduct lesions. The
      outbreak was believed to have originated from two separate introductions into
      commercial layer flocks from premises and by individuals dealing in sales of live
      fowl in the metropolitan New York and New Jersey live-bird markets. Source flocks
      for these markets are primarily in the northeast and mid-Atlantic areas,
      including Pennsylvania. Mixed fowl sold include ducks, geese, guinea hens, quail,
      chukar partridges, and a variety of chickens grown on perhaps hundreds of small
      farms. Infections with the H7N2 AI virus were associated with variable morbidity
      and temporary decreases in egg production ranging from 1.6% to 29.1% in
      commercial egg-laying chickens. Egg production losses averaged 4.0 weeks
      duration. Mortality ranged from 1.5 to 18.3 times normal (mean of 4.3 times
      normal). Duration of mortality ranged from 2 to 13 weeks (average of 3.9 weeks)
      in flocks not depopulated. Lesions observed were primarily oviducts filled with a
      mucous and white gelatinous exudates and atypical egg yolk peritonitis.
      Quarantine of premises and complete depopulation were the early measures employed
      in control of this outbreak. Epidemiological studies suggested that depopulation
      furthered the spread of influenza to nearby flocks. Thereafter, later control
      measures included quarantine, strict biosecurity, and controlled marketing of
      products.

PMID- 14575106
TI  - The impact of a monthly rest day on avian influenza virus isolation rates in
      retail live poultry markets in Hong Kong.
AB  - Retail live poultry markets (LPMs) may act as a reservoir of avian influenza
      viruses (AIV). In this study we test the hypothesis that a rest day in the LPMs
      where the stalls are completely emptied of poultry, cleansed, and restocked will
      reduce the isolation rates of avian influenza viruses. The isolation rate of H9N2
      subtype viruses from chicken was significantly lower after the rest day than
      prior to it, indicating its impact in reducing transmission. In contrast,
      Newcastle disease virus (NDV) isolation rates appear unaffected by this
      intervention, possibly reflecting differences in herd immunity or virus
      transmission dynamics.

PMID- 14575107
TI  - Standardization of an inactivated H17N1 avian influenza vaccine and efficacy
      against A/Chicken/Italy/13474/99 high-pathogenicity virus infection.
AB  - The minimum requirements for assessing the immunogenicity of an experimental
      avian influenza (AI) vaccine prepared from inactivated A/Turkey/Italy/2676/99
      (H7N1) low-pathogenicity (LP) AI (LPAI) virus were determined in chickens of
      different ages. A correlation between the amount of hemagglutinin (HA) per dose
      of vaccine and the protection against clinical signs of disease and infection by
      A/Chicken/Italy/13474/99 highly pathogenic (HP) AI (HPAI) virus was established.
      Depending on the vaccination schedule, one or two administrations of 0.5 microg
      of hemagglutinin protected chickens against clinical signs and death and
      completely prevented virus shedding from birds challenged at different times
      after vaccination.

PMID- 14575108
TI  - Recombinant paramyxovirus type 1-avian influenza-H7 virus as a vaccine for
      protection of chickens against influenza and Newcastle disease.
AB  - Current vaccines to prevent avian influenza rely upon labor-intensive parenteral
      injection. A more advantageous vaccine would be capable of administration by mass
      immunization methods such as spray or water vaccination. A recombinant vaccine
      (rNDV-AIV-H7) was constructed by using a lentogenic paramyxovirus type 1 vector
      (Newcastle disease virus [NDV] B1 strain) with insertion of the hemagglutinin
      (HA) gene from avian influenza virus (AIV) A/chicken/NY/13142-5/94 (H7N2). The
      recombinant virus had stable insertion and expression of the H7 AIV HA gene as
      evident by detection of HA expression via immunofluorescence in infected Vero
      cells. The rNDV-AIV-H7 replicated in 9-10 day embryonating chicken eggs and
      exhibited hemagglutinating activity from both NDV and AI proteins that was
      inhibited by antisera against both NDV and AIV H7. Groups of 2-week-old white
      Leghorn chickens were vaccinated with transfectant NDV vector (tNDV), rNDV-AIV
      H7, or sterile allantoic fluid and were challenged 2 weeks later with
      viscerotropic velogenic NDV (vvNDV) or highly pathogenic (HP) AIV. The sham
      vaccinated birds were not protected from vvNDV or HP AIV challenge. The
      transfectant NDV vaccine provided 70% protection for NDV challenge but did not
      protect against AIV challenge. The rNDV-AIV-H7 vaccine provided partial
      protection (40%) from vvNDV and HP AIV challenge. The serologic response was
      examined in chickens that received one or two immunizations of the rNDV-AIV-H7
      vaccine. Based on hemagglutination inhibition and enzyme-linked immunosorbent
      assay (ELISA) tests, chickens that received a vaccine boost seroconverted to AIV
      H7, but the serologic response was weak in birds that received only one
      vaccination. This demonstrates the potential for NDV for use as a vaccine vector
      in expressing AIV proteins.

PMID- 14575109
TI  - Development of hemagglutinin subtype-specific reference antisera by DNA
      vaccination of chickens.
AB  - Previously, we have shown that intramuscular vaccination of chickens with the
      eukaryotic expression vector (EEV), expressing the influenza H5 hemagglutinin (H)
      protein, can stimulate a measurable and protective antibody response. Based on
      these results, we cloned other H genes from Eurasian H5, North American and
      Eurasian H7, and H15 influenza viruses into the EEV for use in vaccination of
      chickens to produce reference antibodies for diagnostic purposes, such as the
      hemagglutination inhibition (HI) test. Three-week-old specific pathogen free
      (SPF) chickens were vaccinated with 100 microg of EEV mixed with a cationic lipid
      by intramuscular injection. Then the birds were boostered twice at monthly
      intervals after the original vaccination. Measurable antibody titers were present
      for most birds after 1 month and generally increased after each boost. To examine
      the cross reactivity of the sera with other subtypes, HI test was conducted with
      antigens prepared from 15 subtypes of influenza virus. Subtype specificity of the
      antisera prepared by DNA vaccination were comparable or better than the antisera
      prepared by traditional method using whole virus vaccination. Preparation of
      reference antisera by DNA vaccination holds good promise because it is safe and
      allows for the production of H specific antibodies without producing antibodies
      specific to other influenza viral proteins.

PMID- 14575110
TI  - ELISA test for the detection of influenza H7 antibodies in avian sera.
AB  - Using a monoclonal antibody (MAb) specific for the H7 influenza surface
      glycoproteins, a serological enzyme-linked immunosorbent assay (ELISA) test has
      been developed. This MAb was made using the low-pathogenicity (LP) avian
      influenza (AI) strain (BS2676/99) isolated in Italy during a recent outbreak. The
      test is able to detect H7 antibodies in avian sera. The H7 ELISA has a 99%
      concordance of results with the classical hemagglutination inhibition (HI) test.

PMID- 14575111
TI  - Development and preliminary validation of an ad hoc N1-N3 discriminatory test for
      the control of avian influenza in Italy.
AB  - The development of a discriminatory test, based on the differentiation between N1
      and N3 antibodies, to be used in the framework of a vaccination program, based on
      vaccination with a heterologous H7N3 inactivated vaccine against the Italian H7N1
      field virus, is reported. The indirect immunofluorescence antibody (iIFA) assay
      was based on the expression of the N1 protein in a baculovirus system. HighFive
      insect cells were transfected with the recombinant virus and used as an antigen
      in the iIFA test. Preliminary validation on 608 turkey sera yielded relative
      sensitivity and specificity of 98.1% and 95.7%, respectively, when compared to
      the HI test with an almost perfect agreement between the two methods (Kappa value
      = 0.93). It is concluded that the iIFA test is a valid tool for monitoring avian
      influenza infection in a vaccinated population.

PMID- 14575112
TI  - Molecular diagnostics in an insecure world.
AB  - As of October 2001, the potential for use of infectious agents, such as anthrax,
      as weapons has been firmly established. It has been suggested that attacks on a
      nations' agriculture might be a preferred form of terrorism or economic
      disruption that would not have the attendant stigma of infecting and causing
      disease in humans. Highly pathogenic avian influenza virus is on every top ten
      list available for potential agricultural bioweapon agents, generally following
      foot and mouth disease virus and Newcastle disease virus at or near the top of
      the list. Rapid detection techniques for bioweapon agents are a critical need for
      the first-responder community, on a par with vaccine and antiviral development in
      preventing spread of disease. There are several current approaches for rapid,
      early responder detection of biological agents including influenza A viruses.
      There are also several proposed novel approaches in development. The most
      promising existing approach is real-time fluorescent PCR analysis in a portable
      format using exquisitely sensitive and specific primers and probes. The potential
      for reliable and rapid early-responder detection approaches are described, as
      well as the most promising platforms for using real-time PCR for avian influenza,
      as well as other potential bioweapon agents.

PMID- 14575113
TI  - A NASBA method to detect high- and low-pathogenicity H5 avian influenza viruses.
AB  - Nucleic acid sequence-based amplification (NASBA) allows the rapid amplification
      of specific regions of nucleic acid obtained from a diverse range of sources. It
      is especially suitable for amplifying RNA sequences. A NASBA technique was
      developed that allows the detection of avian influenza A subtype H5 from
      allantoic fluid harvested from inoculated chick embryos. The amplified viral RNA
      is detected by electrochemiluminescence. The described NASBA technique is a
      specific, rapid, and sensitive method of detection of influenza A subtype H5
      viruses. More importantly, it can be used to distinguish high- and low
      pathogenicity strains of the H5 subtype.

PMID- 14575114
TI  - RT-PCR-ELISA as a tool for diagnosis of low-pathogenicity avian influenza.
AB  - A one-tube reverse transcriptase/polymerase chain reaction coupled with an enzyme
      linked immunosorbent assay (RT-PCR-ELISA) was developed for the rapid detection
      of avian influenza virus (AIV) in clinical specimens. A total of 419 swab pools
      were analyzed from chickens experimentally infected with low-pathogenicity AIV,
      from wild aquatic birds, and from domestic ducks. The AIV was detected in 32 swab
      pools by RT-PCR-ELISA compared to 23 by virus isolation (VI) in embryonated
      specific pathogen free (SPF) chicken eggs. Thus, 39% more specimens were positive
      by RT-PCR-ELISA than by VI. Two of the twenty-three VI-positive specimens were
      negative when tested by RT-PCR-ELISA. The diagnostic sensitivity and specificity
      of the RT-PCR-ELISA was 91% and 97%, respectively, using VI in SPF eggs as the
      gold reference standard.

PMID- 14575115
TI  - Development of real-time RT-PCR for the detection of avian influenza virus.
AB  - A real-time reverse transcriptase/polymerase chain reaction (RRT-PCR) assay was
      developed using hydrolysis probes for the detection of avian influenza virus
      (AIV) and the H5 and H7 subtypes. The AIV specific primers and probes were
      directed to regions of the AIV matrix gene that are conserved among most type A
      influenza viruses. The H5 and H7 primers and probes are directed to H5 and H7
      hemagglutinin gene regions that are conserved among North American avian
      influenza viruses. The sensitivity and specificity of this RRT-PCR assay was
      compared to virus isolation (VI) in chicken embryos with 1550 clinical swab
      samples from 109 live-bird markets (LBMs) in New York and New Jersey. RRT-PCR
      detected influenza in samples from 61 of 65 (93.8%) of the LBMs that were the
      sources of VI positive samples. Of the 58 markets that were positive for H7
      influenza by hemagglutination inhibition assay, RRT-PCR detected H7 influenza in
      56 markets (96.5%). Too few H5 positive samples were obtained to validate the H5
      RRT-PCR assay in this study. Although RRT-PCR was less sensitive than VI on an
      individual sample basis, this study demonstrated that the AIV and H7 RRT-PCR
      assays are good tools for the rapid screening of flocks and LBMs.

PMID- 14575116
TI  - An update on avian influenza in Hong Kong 2002.
AB  - An outbreak of highly pathogenic avian influenza caused by multiple genotypes of
      H5N1 virus occurred in Hong Kong, commencing in January 2002. Infection in local
      chicken farms was preceded by the detection of virus in multiple retail markets
      and the main poultry wholesale market. The first case of this disease on a local
      farm was detected on February 1, 2002. By February 9, 2002, 15 farms were
      infected, and by late March a total of 22 infected farms had been identified.
      Three main clusters of infected farms were seen, suggesting multiple incursions
      of virus, and subsequent limited lateral spread to neighboring firms. Control of
      this disease has been effected through a combination of quarantine, tightening of
      biosecurity measures, and depopulation of infected and contact farms. About
      950,000 birds have been destroyed. Vaccination using a killed H5 vaccine was
      introduced in April 2002 to farms in one zone where infection has persisted. None
      of the viruses isolated contained the internal genes found in the 1997 H5N1
      virus.

PMID- 14575117
TI  - Development of multiplex real-time RT-PCR as a diagnostic tool for avian
      influenza.
AB  - A multiplex real-time reverse transcriptase-polymerase chain reaction (RRT-PCR)
      assay for the simultaneous detection of the H5 and H7 avian influenza
      hemagglutinin (HA) subtypes was developed with hydrolysis type probes labeled
      with the FAM (H5 probe) and ROX (H7 probe) reporter dyes. The sensitivity of the
      H5-H7 subtyping assay was determined, using in vitro transcribed RNA templates,
      to have a reproducible detection limit for H7 of approximately 10(4) HA gene
      copies and approximately 10(4)-10(5) HA gene copies of H5. A direct comparison of
      H5-H7 multiplex RRT-PCR with hemagglutination inhibition (HI) was performed with
      83 AI RRT-PCR and virus isolation positive tracheal and cloacal swab samples
      obtained from various avian species and environmental swabs from live-bird
      markets in New York and New Jersey. Both multiplex RRT-PCR and HI agreed on the
      subtype determination of 79 (95.2%) of the 83 samples, of which 77 were positive
      for H7 and two were determined to be non-H5/non-H7 subtypes. No samples were
      determined to be the H5 subtype by either assay.

PMID- 14575118
TI  - The effect of various disinfectants on detection of avian influenza virus by real
      time RT-PCR.
AB  - An avian influenza (AI) real time reverse transcriptase-polymerase chain reaction
      (RRT-PCR) test was previously shown to be a rapid and sensitive method to
      identify AI virus-infected birds in live-bird markets (LBMs). The test can also
      be used to identify avian influenza virus (AIV) from environmental samples.
      Consequently, the use of RRT-PCR was being considered as a component of the
      influenza eradication program in the LBMs to assure that each market was properly
      cleaned and disinfected before allowing the markets to be restocked. However, the
      RRT-PCR test cannot differentiate between live and inactivated virus,
      particularly in environmental samples where the RRT-PCR test potentially could
      amplify virus that had been inactivated by commonly used disinfectants, resulting
      in a false positive test result. To determine whether this is a valid concern, a
      study was conducted in three New Jersey LBMs that were previously shown to be
      positive for the H7N2 AIV. Environmental samples were collected from all three
      markets following thorough cleaning and disinfection with a phenolic
      disinfectant. Influenza virus RNA was detected in at least one environmental
      sample from two of the three markets when tested by RRT-PCR; however, all samples
      were negative by virus isolation using the standard egg inoculation procedure. As
      a result of these findings, laboratory experiments were designed to evaluate
      several commonly used disinfectants for their ability to inactivate influenza as
      well as disrupt the RNA so that it could not be detected by the RRT-PCR test.
      Five disinfectants were tested: phenolic disinfectants (Tek-trol and one-stroke
      environ), a quaternary ammonia compound (Lysol no-rinse sanitizer), a peroxygen
      compound (Virkon-S), and sodium hypochlorite (household bleach). All five
      disinfectants were effective at inactivating AIV at the recommended
      concentrations, but AIV RNA in samples inactivated with phenolic and quaternary
      ammonia compounds could still be detected by RRT-PCR. The peroxygen and chlorine
      compounds were effective at some concentrations for both inactivating virus and
      preventing amplification by RRT-PCR. Therefore, the RRT-PCR test can potentially
      be used to assure proper cleaning and disinfection when certain disinfectants are
      used.

PMID- 14575119
TI  - Live-bird market closure activities in the northeastern United States.
AB  - Over the last 10 years, low-pathogenicity avian influenza (LPAI) viruses have
      been isolated from the live-bird markets (LBMs) of the Northeast. Despite
      educational efforts, surveillance, and increased state regulatory efforts, the
      number of positive markets has persisted and increased. In an effort to address
      the continued levels of LPAI in the retail LBM and address the question of
      persistence and circulation of the virus within the LBM system itself, these
      markets were closed for a continuous 3-day period. This effort was a cooperative
      effort between the State Departments of Agriculture and coordinated by the U.S.
      Department of Agriculture and led to the first successful system-wide closure of
      the retail LBMs in the Northeast.

PMID- 14575120
TI  - Low-pathogenicity H7N2 avian influenza outbreak in Virgnia during 2002.
AB  - An outbreak of low-pathogenicity H7N2 avian influenza virus (AIV) in the
      Shenandoah Valley of Virginia during the spring and summer of 2002 affected 197
      farms and resulted in the destruction of over 4.7 million birds. The outbreak
      affected primarily turkey farms (28 breeders, 125 grow out) with some spillover
      into chicken farms (29 breeders, 13 grow out, 2 table-egg layers). Although no
      direct link was established, the strain of H7N2 AIV in this outbreak had a
      molecular fingerprint that was essentially identical to the H7N2 AIV strain that
      has circulated in the live bird markets of the northeastern United States for the
      last 8 yr. After an initial delay caused by lack of viable disposal options,
      depopulation and disposal, primarily in sanitary landfills, was carried out
      within 24 hr of detection of a positive flock. Increased surveillance efforts
      included once-a-week testing of the daily mortality of all poultry farms in the
      region, testing of all breeder farms every 2 wk, and testing of all flocks prior
      to movement for any reason. A statistical sampling of backyard flocks and wild
      birds found no evidence of the virus. The successful eradication of this outbreak
      was the result of the efforts of a highly effective task force of industry,
      state, and federal personnel.

PMID- 14575121
TI  - Isolation and characterization of a low-pathogenicity H7N7 influenza virus from a
      turkey in a small mixed free-range poultry flock in Germany.
AB  - A hemagglutinating virus was isolated from a dead turkey in a small mixed free
      range flock in Southern Germany. It was identified as influenza virus type A of
      subtype H7N7. The pathogenicity was low. An intravenous pathogenicity index of
      0.03 was recorded, and the nucleotide sequencing revealed the amino acid sequence
      NVPEIPKGR*GLFG at the cleavage site of the hemagglutinin. Antibodies as well as
      virus were detected in the affected flock. Further virus spreading to other
      flocks was prevented by stamping out policy. Serological monitoring of contact
      flocks revealed one small backyard flock of 18 hens, which was positive. This
      flock was also destroyed. The origin of the virus could not be identified.

PMID- 14575122
TI  - Type A influenza virus surveillance in free-flying, nonmigratory ducks residing
      on the eastern shore of Maryland.
AB  - Virus surveillance in free-flying, nonmigratory ducks living on the eastern shore
      of Maryland indicated that influenza A viruses were introduced into the area or
      that the prevalence of endemic infections increased between July 15 and August
      27, 1998. Cloacal swabs collected between May 28 and July 15, 1998, were negative
      for influenza A virus recovery (0/233), whereas 13.9% (29/209) of swabs collected
      between August 27 and September 2, 1998, were positive for influenza A virus
      recovery. Five hemagglutinin subtypes (H2, H3, H6, H9, and H12), six
      neuraminidase subtypes (N1, N2, N4, N5, N6, and N8), and nine HA-NA combinations
      were identified among 29 influenza A isolates. Interestingly, 18 of the 29
      isolates initially appeared to contain two or more HA and/or NA subtypes. The
      free-flying, nonmigratory ducks served as excellent sentinels for the early
      detection of type A influenza viruses in the southern half of the Atlantic
      Migratory Waterfowl Flyway during the earliest phase of the yearly southern
      migration.

PMID- 14575123
TI  - Low-pathogenicity avian influenza virus in live bird markets--what about the
      livestock area?
AB  - Low-pathogenic avian influenza virus (AV) continues to be isolated from the live
      bird markets (LBMs) in the Northeasten United States. Recent years have seen
      increasing numbers of these markets opening and an expansion of the type of
      animals they sell in conjunction with traditional live poultry. Specific-pathogen
      free chickens were released into the livestock area of 13 New York City LBMs and
      then tested for evidence of AIV. We were able to recover virus or demonstrate
      seroconversion among the chickens introduced to four of the markets.

PMID- 14575124
TI  - Land-based birds as potential disseminators of avian mammalian reassortant
      influenza A viruses.
AB  - Chickens, quail, and other land-based birds are extensively farmed around the
      world. They have been recently implicated in zoonotic outbreaks of avian
      influenza in Hong Kong. The possibility that land-based birds could act as mixing
      vessels or disseminators of avian/mammalian reassortant influenza A viruses with
      pandemic potential has not been evaluated. In this report, we investigated
      whether chickens and Japanese quail are susceptible to a mammalian influenza
      virus (A/swine/Texas/4199-2/98 [H3N2]). This virus did not grow in chickens and
      replicated to low levels in Japanese quail but did not transmit. Replacing the H3
      gene of this virus for one of the avian H9 viruses resulted in transmission of
      the avian/swine reassortant virus among quail but not among chickens. Our
      findings demonstrated that Japanese quail could provide an environment in which
      viruses like the A/swine/Texas/4199-2/98 [H3N2] virus could further reassort and
      generate influenza viruses with pandemic potential.

PMID- 14575125
TI  - Sequence of HA gene of avian influenza A/Chicken/Guangdong/SS/1994 (H9N2) virus.
AB  - The RNA of the hemagglutinin (HA) gene of A/Chicken/Guangdong/SS/1994 (H9N2) was
      reverse transcription-polymerase chain reaction amplified, and the cDNA was
      cloned into a plasmid vector. The complete coding sequence of the HA gene was
      sequenced and included 1683 nucleotides, which encoded for a protein of 560 amino
      acids. The potential glycosylation sites related to HA protein function were
      highly conserved. The amino acid sequence of the HA proteolytic cleavage was G-S
      S-R/G. This cleavage site sequence is compatible with a low-pathogenic avian
      influenza virus. Sequence comparison of this HA gene with other H9 influenza
      virus sequences in the GenBank database showed a 82%-97% nucleotide and amino
      acid sequence similarity.

PMID- 14575126
TI  - Neurological manifestations of avian influenza viruses in mammals.
AB  - The H5N1 viruses isolated from humans in Hong Kong directly infected both mice
      and ferrets without prior adaptation to either host. Two representative viruses,
      A/Hong Kong/483/97 (HK/483) and A/Hong Kong/486/97 (HK/486) were equally virulent
      in outbred ferrets but differed in their virulence in inbred mice. Both HK/483
      and HK/486 replicated systemically in ferrets and showed neurologic
      manifestations. In contrast, intranasal infection of mice with HK/483, but not
      HK/486, resulted in viral spread to the brain, neurologic signs, and death.
      However, HK/486 was able to replicate in the brain and induce lethal disease
      following direct intracerebral inoculation.

PMID- 14575127
TI  - Generation and characterization of an H9N2 cold-adapted reassortant as a vaccine
      candidate.
AB  - H9N2 subtype avian influenza viruses have been identified in avian species
      worldwide, and infections in pigs were confirmed in Hong Kong in 1998.
      Subsequently, H9N2 viruses were isolated from two children in Hong Kong in 1999,
      and five human infections were reported from China, raising the possibility that
      H9N2 viruses pose a potential pandemic threat for humans. These events prompted
      us to develop a vaccine candidate to protect humans against this subtype of
      influenza A viruses. Reassortant H1N1 and H3N2 human influenza A viruses with the
      six internal gene segments of A/Ann Arbor/6/60 (H2N2)(AA) cold-adapted (ca) virus
      have been tested extensively in humans and have proved to be attenuated and safe
      as live virus vaccines. Using classical genetic reassortment, we generated a
      reassortant that contains the hemagglutinin and neuraminidase genes from
      A/chicken/Hong Kong/G9/97 (H9N2) and six internal gene segments from the AAca
      virus. The G9/AAca reassortant virus exhibits the ca phenotype and the
      temperature-sensitive phenotypes of the AAca virus and was attenuated in mice.
      The reassortant virus was immunogenic and protected mice from wild-type H9N2
      virus challenge. The G9/AAca virus bears the in vitro and in vivo phenotypes
      specified by the AAca virus and will be evaluated as a potential vaccine
      candidate in humans.

PMID- 14575128
TI  - Mechanisms of pathogenicity of influenza A (H5N1) viruses in mice.
AB  - Avian-like H5N1 influenza viruses isolated from humans in 1997 were shown to have
      two distinct pathogenic phenotypes in BALB/c mice, after intranasal inoculation
      and without prior adaptation to this host. To further understand the mechanisms
      of H5N1 pathogenicity, we investigated the consequences of the mute of viral
      inoculation on morbidity and mortality, viral replication in pulmonary and
      systemic organs, and lymphocyte depletion. This study demonstrates the importance
      of extrapulmonary spread and replication, particularly in the brain, for the
      lethality of H5N1 viruses.

PMID- 14575129
TI  - Pathogenesis of and immunity to a new influenza A (H5N1) virus isolated from duck
      meat.
AB  - The outbreak of avian influenza H5N1 in Hong Kong in 1997 raised concerns about
      the potential for the H5 subtype to cause a human pandemic. In 2001 a new H5N1
      virus, A/Duck Meat/Anyang/AVL-1/2001 (A/Dkmt), was isolated from imported duck
      meat in Korea. The pathogenesis of this virus was investigated in mice. A/Dkmt
      virus had low infectivity but was lethal for mice at high doses, and at lethal
      doses, the virus replicated in the brains of infected mice. A/Dkmt virus cross
      reacted poorly with ferret antisera raised against human H5N1 viruses, but prior
      infection with A/Dkmt virus protected mice from death after secondary infection
      with human H5N1 virus.

PMID- 14575130
TI  - Assaying susceptibility of avian and other influenza A viruses to zanamivir:
      comparison of fluorescent and chemiluminescent neuraminidase assays.
AB  - Zanamivir has been shown to inhibit both human and avian influenza viral
      neuraminidases (NAs) and has been approved in several countries for the treatment
      and prophylaxis of influenza infection. Reliable monitoring of drug resistance is
      important for assessment of the impact of drug therapy on circulating virus
      populations. This study compares the current fluorometric (FL) method for
      evaluating zanamivir susceptibility with a recently developed chemiluminescent
      (CL) NA activity assay using viruses representative of all nine NA subtypes. The
      CL assay displayed signal/noise ratios that are 50-100 times greater than those
      associated with the FL assay. Human H3N2 strains appeared to exhibit greater NA
      activity relative to avian subtypes with the FL substrate but not with the CL
      substrate. Additionally, the CL assay remained linear over three orders of
      magnitude compared to only one order of magnitude for the FL assay. Four of the
      nine NA subtypes tested in this study displayed slightly higher inhibitor
      concentration that inhibits 50% of neuraminidase activity values by CL than by
      FL, while four displayed the opposite effect. Implications for the routine
      determination of resistance to NA inhibitors are discussed.

PMID- 14575131
TI  - Avian embryo susceptibility to Italian H7N1 avian influenza viruses belonging to
      different lineages.
AB  - An immunohistochemical investigation was performed to assess tissue tropism and
      viral replication of Italian H7N1 isolates belonging to different lineages in
      developing chicken, turkey, Muscovy duck, and mallard duck embryos. Low
      pathogenic avian influenza (LPAI)isolates were selected on the basis of the
      location in the phylogenetic tree; a progenitor strain, A/turkey/Italy/977/V99
      (exhibiting no additional glycosylation sites, nAGS), strain
      A/turkey/Italy/2379/V99 (AGS in position 123), and strain A/turkey/Italy/3675/V99
      (AGS in position 149) were selected. The latter two strains belonged to distinct
      lineages originating from the pool of progenitor strains. The highly pathogenic
      avian influenza (HPAI) isolate A/turkey/Italy/4580/V99 was also included in the
      test. All the embryos tested supported the growth of HPAI. The LPAI isolates
      replicated readily in the allantoic layer of the chorioallantoic membrane of all
      the species tested and did not replicate to detectable levels in the developing
      chicken, turkey, and Muscovy duck embryos. In contrast, they replicated to
      different extents in the respiratory tract of the developing mallard embryo. The
      findings indicate that the pathogenesis of LPAI infections in mallard embryos is
      different to that observed in other species and should be investigated further.

PMID- 14575132
TI  - Pathogenesis of H7 influenza A viruses isolated from ostriches in the homologous
      host infected experimentally.
AB  - Infections of ostriches with avian influenza A viruses are generally associated
      with clinical disease, but the occasional high mortality in young birds does not
      appear to be related directly to virus pathotype. In this study we investigated
      the pathogenesis of two H7 viruses for 11-wk-old ostriches inoculated
      intranasally, and clinical symptoms, virus excretion, and immune response were
      studied. One of the viruses (A/Ostrich/Italy/1038/00) was highly pathogenic for
      chickens, whereas the other (A/Ostrich/South Africa/1609/91) was of low
      pathogenicity for chickens. Clinical signs in ostriches receiving virulent virus
      were slight depression and hemorrhagic diarrhea, while the group receiving
      avirulent virus was clinically normal except for green diarrhea. Both viruses
      were transmitted to in-contact sentinel birds housed with the infected groups 3
      days postinfection. Postmortem examination of the birds infected (including the
      sentinel bird) with virus highly pathogenic for chickens were grossly normal
      except for localized pneumonic lesions. The results of the study are presented
      and discussed.

PMID- 14575133
TI  - Differences between influenza virus receptors on target cells of duck and chicken
      and receptor specificity of the 1997 H5N1 chicken and human influenza viruses
      from Hong Kong.
AB  - To study whether influenza virus receptors in chickens differ from those in other
      species, we compared the binding of lectins and influenza viruses with known
      receptor specificity to cell membranes and gangliosides from epithelial tissues
      of ducks, chickens, and African green monkeys. We found that chicken cells
      contained Neu5Ac alpha(2-6)Gal-terminated receptors recognized by Sambucus nigra
      lectin and by human viruses. This finding explains how some recent H9N2 viruses
      replicate in chickens despite their human virus-like receptor specificity. Duck
      virus bound to gangliosides with short sugar chains that were abundant in duck
      intestine. Human and chicken viruses did not bind to these gangliosides and bound
      more strongly than duck virus to gangliosides with long sugar chains that were
      found in chicken intestinal and monkey lung tissues. Chicken and duck viruses
      also differed by their ability to recognize the structure of the third sugar
      moiety in Sia2-3Gal-terminated receptors. Chicken viruses preferentially bound to
      Neu5Ac alpha(2-3)Gal beta(1-4)GlcNAc-containing synthetic sialylglycopolymer,
      whereas duck viruses displayed a higher affinity for Neu5Ac alpha(2-3)Gal beta(1
      3)GalNAc-containing polymer. Our data indicate that sialyloligosaccharide
      receptors in different avian species are not identical and provide a potential
      explanation for the differences between the hemagglutinin and neuraminidase
      proteins of duck and chicken viruses.

PMID- 14575134
TI  - Plaque morphology of Italian H7N1 LPAI isolates in MDCK cells and in primary
      cells of different avian species.
AB  - The morphology of plaques induced by Italian, H7N1, low-pathogenic avian
      influenza (LPAI) viruses belonging to different lineages was investigated in
      primary chicken, turkey, Muscovy duck, and mallard duck kidney cells and in MDCK
      cells in the absence of trypsin. LPAI isolates were selected on the basis of the
      location in the phylogenetic tree: 977/V99 (located at the root, no additional
      glycosylation site [nAGS]), 2379N99 (AGS in position 123), and 3675/V99 (AGS in
      position 149). Different isolates did not induce plaques with a statistically
      significant different size in MDCK cells. However, in primary cells of different
      avian origin, the presence or absence of AGS significantly influenced plaque
      size. Generally speaking, 977N99 was the least efficient at plaquing in all
      cells, while 2379/V99 (AGS in position 123) plaqued more efficiently in turkey
      cells and 3675/V99 (AGS in position 149) in chicken cells. The presence of either
      AGS induced statistically significant larger plaques in cells of waterfowl
      origin.

PMID- 14575135
TI  - Differences between HA receptor-binding sites of avian influenza viruses isolated
      from Laridae and Anatidae.
AB  - A comparative study of the hemagglutinin (HA) receptor binding site (RBS) of a
      number of H13 influenza viruses isolated from Laridae family of birds (gulls) and
      other influenza viruses obtained from the Anatidae family (ducks) was conducted.
      The affinity of all viruses to alpha N-acetylneuraminic acid (Neu5Ac alpha),
      3'sialyllactose (3'SL), and sialylglycopolymers bearing 3'-sialyl(N
      acetyllactosamine) (3'SLN-PAA), [Neu5Ac alpha(2-3)Gal beta(1-4)][-Fuc alpha(1
      3)]GlcNAc beta (SLe(x)-PAA), and [Neu5Ac alpha(2-3)Gal beta(1-3)][-Fuc alpha(1
      4)]GlcNAc beta (SLe(a)-PAA), was determined. The last three polymer
      glycoconjugates were synthesized for determining the contribution of carbohydrate
      chains after the galactose link to the binding with the receptor. The difference
      in affinity between 3'SL and Neu5Ac alpha in all studied H13 viruses is small,
      which indicates a less significant role of the galactose moiety in the binding to
      the receptor. The results of virus binding with polymer sialylglycoconjugates
      indicates that the method of linking, the third monosaccharide moiety, and the
      presence of an extra fucose substitute in this moiety may influence the binding
      considerably. For viruses isolated from ducks, the suitable polymer is SLe(a)-PAA
      (i.e., a 1-3 linkage between galactose and glucosamine is optimal). This finding
      is in accord with the data that H13 viruses isolated from the gulls differ based
      on their ability to interact with polymer sialylglycoconjugates. The affinity to
      all three polymers is uniform, and the presence of GlcNAc-linked fucose does not
      prevent the binding. A comparative analysis of six sequenced HA H13 viruses and
      other subtype viruses showed presence of substantial differences in the
      composition of amino acids of this region in H13 viruses.

PMID- 14575136
TI  - Descriptive and surveillance studies of suppliers to New York and New Jersey
      retail live-bird markets.
AB  - Low pathogenicity avian influenza virus (AIV) H7N2 has been isolated since 1994
      from retail live-bird markets (LBMs) in the northeastern United States. This
      study examines the suppliers to the LBMs in New York and New Jersey. In 2001, 185
      supplier premises in nine states were surveyed for the presence of AIV by virus
      isolation (VI) in embryonating chicken eggs. No H7 or H5 virus was isolated. In
      addition, 104 producer premises in two states were serologically negative for H7
      and H5 AIV. Information on management practices was obtained via questionnaire
      for 191 premises in 12 states. The survey results suggest that current
      biosecurity practices at supplier premises could be improved, especially
      regarding movement of birds. The study supports the hypothesis that H7N2 AIV is
      primarily maintained within the LBMs and, if reintroduction from suppliers is
      occurring, it is likely reintroduced at a very low level or from suppliers not
      included in this study.

PMID- 14575137
TI  - Avian influenza attributable to serovar H7N1 in light layers in Italy.
AB  - In March 1999 a syndrome characterized by depression, anorexia, fever, and
      respiratory and enteric signs appeared in many flocks of turkeys and, to a lesser
      extent, chickens in the densely populated poultry-rearing regions of Northeastern
      Italy. Initially the disease was characterized by sinusitis, tracheitis,
      peritonitis, and pancreatitis. The responsible agent was identified as low
      pathogenicity (LP) avian influenza (AI) of H7N1 subtype. Concerning the light
      layers, the mortality was variable, from 1.7% to 9.5%, whereas egg production
      decreased by 10% to 40%. According to the epidemiologic data, chickens seemed to
      be less sensitive to the virus than were turkeys. Nine months later, the AI virus
      changed to a highly pathogenic (HP) AI virus and affected, besides turkeys, a
      great number of pullet and layer flocks, with high mortality (80%-100%) in a few
      days. However, the course of disease was more prolonged in pullets. Within 3 1/2
      mo, over 100 outbreaks were reported. Following the HPAI outbreaks, in late 2000
      and early 2001, LPAI reemerged, but only one flock of layers was affected.

PMID- 14575138
TI  - Strategies to improve protection against low-pathogenicity H7 avian influenza
      virus infection using DNA vaccines.
AB  - Eukaryotic expression plasmids encoding either the avian influenza hemagglutinin
      or matrix genes (pCMV-HA and pCMV-M, respectively) were constructed. The viral
      genes were derived from a low-pathogenicity H7N1 strain, A/Chicken/Italy/1067/99,
      isolated during the 1999-2001 epizootic in Italy. The plasmid was administered to
      4-to-5-wk-old specific-pathogen-free chickens by several different injection
      methods. For the initial studies comparing methods of vaccine injection, results
      were compared based on hemagglutination inhibition (HI) response following
      immunization with pCMV-HA. Additional studies with coadministration of both pCMV
      HA and pCMV-M was evaluated based on HI response and viral isolation after
      homologous challenge. Preliminary results indicate that a device intended to
      inject insulin in humans (Medijector) and the coadministration of both plasmids
      improved protection against H7 infection.

PMID- 14575139
TI  - Detection of H7 avian influenza virus directly from poultry specimens.
AB  - Using clinical materials from experimentally infected poultry, we established an
      effective method for the preparation of viral RNA directly from tissue samples
      and eggs. Furthermore, our type A-specific matrix reverse transcription
      polymerase chain reaction (RT-PCR) test was improved, and an H7 subtype-specific
      nested RT-PCR, which includes the hemagglutinin cleavage site, was designed. Both
      RT-PCR systems proved to be as sensitive as virus isolation. In addition, the
      labeled H7 HA-nested PCR primers were suitable for sequencing of the PCR
      products. The RT-PCR amplification of viral RNA and sequencing of the PCR product
      allows for the sensitive and rapid differentiation between low-pathogenic and
      highly pathogenic avian influenza viruses.

PMID- 14575140
TI  - Rapid diagnosis of highly pathogenic avian influenza using pancreatic impression
      smears.
AB  - The 1985 outbreak of high-pathogenicity avian influenza (HPAI) in Victoria,
      Australia, took 5 days to confirm by standard laboratory tests, during which time
      infected chickens continued excreting virus, thus creating the opportunity for
      transmission to other farms. An immunofluorescence test for the detection of
      viral antigen in tissue impression smears was evaluated as a rapid diagnostic
      test for HPAI virus infections of poultry. Several test configurations were
      compared for background reactions and strength of fluorescence, with the optimum
      combination found to be an influenza A group-specific monoclonal antibody,
      detected by an anti-mouse fluorescein isothiocyanate conjugate.
      Immunohistochemical examination of tissues from chickens experimentally infected
      with low-pathogenicity and HPAI viruses identified the pancreas as the organ most
      consistently containing high concentrations of HPAI viral antigen. This test has
      since been used in Australia in the rapid laboratory confirmation of three avian
      influenza outbreaks and in showing that numerous other suspect cases were not
      caused by avian influenza.

PMID- 14575141
TI  - Validation of egg yolk antibody testing as a method to determine influenza status
      in white leghorn hens.
AB  - Determination of the avian influenza (AI) status of a flock has traditionally
      been done by detection of serum antibodies. However, for many diseases, detection
      of antibodies in egg yolk has been effective in monitoring the disease status of
      laying flocks. This study compared the utility of egg yolk vs. serum for
      determining AI status in laying hen flocks. Specific-pathogen-free white leghorn
      hens were inoculated via the respiratory tract with a low-pathogenic H7N2 AI
      virus or sterile allantoic fluid or subcutaneously with an inactivated oil
      emulsion vaccine produced from the same AI virus or normal allantoic fluid.
      Antibody levels were determined by the agar gel immunodiffusion (AGID) test, the
      hemagglutination-inhibition (HI) test, and the enzyme-linked immunosorbent assay
      (ELISA). Anti-influenza antibodies were detected in sera of all live virus
      inoculated hens by day 7 postinoculation (PI) (AGID and ELISA tests), but
      detection of antibodies in egg yolk was delayed by a few days, with all being
      positive by day 14 PI. Sera from all vaccinated hens were positive by day 14 PI
      (AGID and ELISA tests), and egg yolk was positive by day 18 PI. The HI test was
      less sensitive than the ELISA and AGID tests in detecting anti-influenza
      antibodies in both sera and yolk. Serum and yolk from all control birds remained
      negative throughout the study. These studies show that currently used serologic
      tests can detect antibodies in serum and yolk samples from hens exposed to live
      AI virus or from those that have been vaccinated. Antibody is detected earlier in
      the serum than in the yolk and antibody is detected earlier from birds exposed to
      a live infection compared to birds vaccinated with an inactivated oil emulsion
      vaccine.

PMID- 14575142
TI  - Development of a highly sensitive screen for influenza A in guano and its
      application in the search for ancient RNA preserved under Antarctic Adelie
      penguin colonies.
AB  - We have developed a reverse transcriptase polymerase chain reaction (RT-PCR)
      based assay to detect influenza A in guano samples as part of our program to
      investigate ancient viral RNA from under Antarctic Adelie penguin (Pygoscelis
      adeliae) colonies. Of five extraction protocols tested (RNeasy, GTC TRIZOL, GTC
      Silica, Rnaid, and AGPC), AGPC proved to be the most consistent and sensitive to
      low concentrations of influenza, but further purification with commercial viral
      nucleic acid spin filter system was still required to remove remaining PCR
      inhibitors. RT-PCR was then performed on the eluent and 650 bases of the M1 gene
      were amplified. The assay was found to be able to detect as little as 100 microl
      of 0.1 hemagglutination units (HU)/ml influenza.

PMID- 14575143
TI  - Pathogenicity of a ratite-origin influenza A H5 virus in ostriches (Struthio
      camelus).
AB  - Ostriches were inoculated with a highly pathogenic avian influenza (HPAI) virus
      of ratite origin, A/emu/Texas/39924/93 (H5N2) done clB. The aim of this study was
      to evaluate the pathogenicity of this isolate for ostriches and to assess the
      ability of routine virologic and serologic tests to detect infection. Avian
      influenza virus (AIV) was isolated from tracheal swabs from 2 to 12 days
      postinfection and from cloacal swabs from 3 to 10 days postinfection. AIV was
      also isolated from a wide range of tissues. Birds seroconverted as early as 7
      days postinfection. This study indicates that HPAI virus of ratite origin
      replicates extensively in infected ostriches without causing significant clinical
      disease or mortality.

PMID- 14575144
TI  - Characterization of avian influenza virus isolates submitted to the National
      Centre for Foreign Animal Disease between 1997 and 2001.
AB  - The National Centre for Foreign Animal Disease (NCFAD) in Winnipeg, Manitoba, is
      the Canadian Food Inspection Agency's (CFIA) newest high biocontainment
      laboratory. One of the functions of the NCFAD is to serve as a national reference
      laboratory for avian influenza. Between 1997 and 2001, 15 avian influenza virus
      isolates were characterized. These isolates originated from domestic poultry,
      imported caged birds held in quarantine, and wild birds. Diagnostic specimens
      were submitted to the NCFAD by CFIA field veterinarians, provincial veterinary
      diagnostic laboratories, and veterinary colleges. Characterization of isolates
      included the determination of H and N subtypes: H1, H6, H7, and H10 subtypes were
      isolated from domestic poultry; H3, H4, and three H13 viruses were isolated from
      water fowl, and six H3 viruses were isolated from caged birds being held in
      import quarantine. Selected isolates were characterized with respect to their
      pathogenic potential by intravenous inoculation of 4-to-6-wk-old chickens. A
      molecular-based protocol was used to assess the pathogenicity of one H7 isolate.
      During this period, work was also carried out toward validating our molecular
      pathotyping protocol for avian influenza viruses with H5 and H7 hemagglutinin
      subtypes.

PMID- 14575145
TI  - The occurrence of avian influenza A subtype H6N2 in commercial layer flocks in
      Southern California (2000-02): clinicopathologic findings.
AB  - Between February 2000 and February 2002, the California Animal Health and Food
      Safety Laboratory System diagnosed 26 cases of low-pathogenic H6N2 avian
      influenza from 12 commercial egg-laying farms. The most common gross and
      histologic lesions observed in infected chickens were fibrinous yolk peritonitis,
      salpingitis, oophoritis, and nephritis. Edema of the mesentery of the oviduct and
      pale, swollen kidneys were also observed. Mortality in infected flocks ranged
      from 0.25% to 3%, and egg production dropped 7% to 40%.

PMID- 14575146
TI  - Recombinant protein comprising multi-neutralizing epitopes induced high titer of
      antibodies against influenza A virus.
AB  - In previous studies, we suggested that epitope-vaccine might be a new strategy
      against virus infection. Based on this hypothesis, we designed and expressed a
      recombinant immunogen (multi-epitope-peptide) comprising repeats of three
      neutralizing-epitopes (neutralizing epitopes: aa92-105, 127-133 and 183-195) of
      hemagglutininin (HA) of influenza virus (H3N2) in E. coli. After vaccination, the
      recombinant multi-epitope protein could induce a high level of antibodies with
      predefined multi-epitope-specificity in mice and rabbits. The epitope-specific
      antibodies in sera were tested using three different epitope-peptides (synthetic
      peptides) in ELISA assay, and the serum dilutions from 1 : 6400 to 1 : 25600 were
      confirmed. In western blot analysis, both the antiserum and the antibodies
      purified by synthetic epitope-peptide coupled sepharose columns could recognize
      natural HA from influenza virus particles (strain A/Wuhan/359/95 H3N2). In
      hemagglutination inhibition (HI) tests, these three antisera at the dilutions
      from 1 : 20 to 1 : 80 showed inhibitory activity. Interestingly, antisera and
      purified antibodies induced by the epitope-vaccine could partially inhibit plaque
      formation of influenza virus (strain A/Wuhan/359/95) on MDCK cell monolayers.
      These results suggest that the recombinant multi-epitope vaccine can
      simultaneously induce multi-antiviral activities against influenza virus, which
      may provide a new way to develop effective vaccines against influenza virus.

PMID- 14575147
TI  - Effects of histamine on functional maturation of dendritic cells.
AB  - There is increasing evidence that histamine affects dendritic cell (DC)
      activation, maturation, and preference for Th1/Th2 differentiation. In this paper
      we report that histamine affects interleukin (IL)-12 and IL-6 production in an
      immature DC (iDC) line derived from murine spleen. Histamine treatment of iDC
      significantly increased the IL-12 p40 mRNA and protein levels compared to
      histamine untreated iDC. In the presence of tumor necrosis factor (TNF)-alpha
      histamine also increased IL-12 p40 and IL-6 production. However, histamine
      significantly decreased IL-12 p40 production by lipopolysaccharide (LPS)
      stimulated DC in a concentration dependent manner. When expressions of histamine
      H1 (H1R) and H2 (H2R) receptors in DC were analyzed by RT-PCR, both receptors
      were down-regulated after LPS or TNF-alpha stimulation compared to unstimulated
      iDC. Histamine treatment significantly increased the expression of H2R mRNA in
      iDC and H1R mRNA in LPS-activated DC. However, histamine treatment decreased the
      expression of both histamine receptors in TNF-alpha-stimulated DC. Similar
      results were obtained by flow cytometry with FITC-conjugated histamine. These
      results demonstrate that histamine can regulate the expression of its own
      receptors and activate iDC, which may influence subsequent functional states of
      mature DC in a maturation signal-dependent manner. Consequently, histamine may
      contribute to an immune response outcome.

PMID- 14575148
TI  - Characterization of porcine plasma ficolins that bind Actinobacillus
      pleuropneumoniae serotype 5B.
AB  - Ficolins are collagenous lectins implicated in resistance to infection by some
      micro-organisms with surfaces containing N-acetylglucosamine residues. Pigs have
      two known ficolin genes, alpha and beta, but ficolins in pig plasma appear in
      various electrophoretic forms, the origin and function of which are unclear. In
      this investigation the forms of ficolin in pig plasma that bind to the pneumonic
      pathogen Actinobacillus pleuropneumoniae serotype 5b (APP5) were compared with
      affinity-purified porcine plasma ficolins. APP5-bound ficolins consisted of two
      distinct multimeric (non-denatured) forms composed of subunits that migrated as
      multiple 38,40 and 42 kDa forms (apparent MW) with pI range 5.2-6.0. The APPS
      binding forms of ficolin were consistent with ficolin alpha and were
      indistinguishable from affinity-purified plasma ficolins by peptide mass
      fingerprint analysis. Subunit bands separated by 2D-PAGE were consistent with
      porcine ficolin alpha. Affinity-purified plasma ficolins had a major subunit mass
      of 35081 Da by MALDI-TOF MS. Affinity-purified ficolins digested with N
      glycosidase F retained APP5-binding activity and migrated faster as a single band
      of 38 kDa. These studies indicate that ficolin alpha is the major APPS-binding
      form in porcine plasma and suggest that N-glycosylation contributes to the
      apparent electrophoretic heterogeneity of porcine ficolins but is not required
      for APP5-binding activity.

PMID- 14575149
TI  - Extrathymic T cells expand in nude mice following different allogeneic stimuli.
AB  - We studied extrathymic lymphocyte populations expanded in nude mice after
      allogeneic stimuli. These were either cells from different tissues or
      Immunoglobulin (Ig). Although the cells transferred, obtained from Thy-1.1+
      donors, were able to induce similar increase in the nude host Thy-1.2+
      population, the expanded populations could be qualitatively distinguished from
      each other by their different expression of mature T cell molecules and by their
      functional profile. The extrathymic lymphocytes expanded in animals receiving
      allogeneic fetal thymocytes (FT) were preferentially CD4+ cells and could confer
      a functional immunocompetent system to the nude host, able to reject allogeneic
      skin grafts. In contrast, allogeneic adult red blood cells (RBC) led to the
      expansion of a CD8+ population and to an auto-reactive profile, resulting in the
      rejection of syngeneic skin grafts by most of the nude hosts. Neither of these
      profiles was achieved with the other stimuli. These findings support the view
      that different activation pathways and/or regulatory interactions may lead to the
      development of distinct extrathymic populations.

PMID- 14575150
TI  - Identification of genes expressed in tumor-associated macrophages.
AB  - Most malignant tumors contain so-called tumor-associated macrophages (TAM) as a
      major component of their leukocytic infiltrate. To investigate the impact of the
      tumor microenvironment on activation and differentiation of macrophages, we
      established a 3-dimensional model system by culturing human monocytes within
      multicellular tumor spheroids. After 7 days, monocyte-derived TAM were isolated
      and analyzed for phenotypic alterations as compared to macrophages cultured
      without tumor cell contact. We found the known macrophage differentiation marker
      Carboxypeptidase M to be suppressed while CD14, HLA-DR, and CD16 were up
      regulated. Using Differential Display, we identified several genes that were
      differentially expressed between TAM and control macrophages. Prolidase, a
      peptidase known to influence the chemoattraction of neutrophils and macrophage
      activity, was down-regulated in TAM. In contrast, the Toll-like receptor family
      related molecules MD-1 and RP105 were up-regulated by tumor cell contact, both at
      the RNA and protein level. From our data we conclude that TAM represent a distict
      macrophage population characterized by low expression of differentiation
      associated macrophage antigens but also by a constitutive state of activation.

PMID- 14575151
TI  - Rapid development of Th2 activity during T cell priming.
AB  - The paradigm of T helper-1 (Th-1) and Th-2 cells developing from non-committed
      naive precursors is firmly established. Th1 cells are characterized by IFNgamma
      production and, in mice, the selective switching to IgG2a. Conversely IL-4
      production and selective switching to IgG1 and IgE characterize Th2 cells.
      Analysis of Th2 induction in vitro indicates that this polarization develops
      gradually in T cells activated by anti-CD3 in the presence of IL-4; conversely
      anti-CD3 and IFNgamma induce Th1 cells. In this report, we explore evidence that
      indicates that the T helper cell polarization in vivo cannot solely be explained
      by the cytokine environment. This is provided by studying the early acquisition
      of Th1 and Th2 activities during responses to a mixture of Th1 and Th2-inducing
      antigens. It is shown that these divergent forms of T cell help can rapidly
      develop in cells within a single lymph node. It is argued that early polarization
      to show Th-1 or Th-2 behavior can be induced by signals delivered during cognate
      interaction between virgin T cells and dendritic cells, in the absence of type 1
      or type 2 cytokines. This contrasts with the critical role of the cytokines in
      reinforcing the Th-phenotype and selectively expanding T helper clones.

PMID- 14575152
TI  - Pathomechanisms of paraneoplastic myasthenia gravis.
AB  - Thymic T cell development is characterized by sequential selection processes to
      ensure generation of a self-tolerant, immuncompetent mature T cell repertoire.
      Malfunction of any of these selection processes may potentially result in either
      immunodeficiency or autoimmunity. Myasthenia gravis (MG) is a typical autoimmune
      manifestation of thymic epithelial tumors (thymomas) and is related to the
      capacity of these tumors to generate and export mature T cells. Analysis of the
      factors that lead to autoimmunization in thymomas will help to understand the
      mechanisms that prevent MG under physiological conditions in humans. In a
      comparison of MG(+) and MG(-) thymomas, we could show that only thymomas capable
      of generating mature CD45RA+CD4+ T cells are associated with MG (p < 0.0001),
      while terminal thymopoiesis was abrogated in MG(-) thymomas. In particular,
      acquisition of the CD27+CD45RA+ phenotype appears to be a critical checkpoint of
      late T cell development in the human thymus and may play an important role in the
      prevention of autoimmunity. Moreover, MG(-) thymomas were virtually depleted of
      regulatory (CD4+CD25+) T cells (regT), while regT were readily detectable in
      MG(+) thymomas, albeit at significantly reduced numbers compared to control
      thymuses. Thus, in MG(+) thymoma patients, thymectomy apparently also results in
      removal of a regulatory T cell pool and may explain the frequent temporary
      postoperative deterioration of MG in these patients.

PMID- 14575154
TI  - The effect of dosage, gestational age and splenectomy on anti-IgM interception of
      prenatal B-cell development in sheep.
AB  - The administration of a single bolus of anti-IgM antibody to foetal lambs early
      in pregnancy produces prolonged B-cell depletion. The present study investigated
      this depletion by examining the effect, on B-cell development in the ileal
      Peyer's patches, of varying the timing and dosage of antibody administration and
      by supplementing anti-IgM with surgical splenectomy. The capacity of a 1 mg bolus
      of anti-IgM to deplete Peyer's patches of B cells was lost if its administration
      was deferred until two thirds of the way through pregnancy, but persisted beyond
      this time if weight-adjusted doses were used. Splenectomy of the foetus performed
      at an earlier age failed to extend the age at which a 1 mg dose of antibody
      remained effective. As the concentration of murine immunoglobulin in foetal serum
      was greatly reduced after 21 days, it is inferred that ongoing suppression of B
      cell development is not dependent on the continued presence of murine
      immunoglobulin. The enduring nature of suppression could be attributable to a
      limited period during which differentiation of B cells from stem cells normally
      occurs, although further studies will be needed to investigate this and other
      possible explanations for the effect of anti-IgM treatment on prenatal B-cell
      development in sheep.

PMID- 14575153
TI  - CTLA-4 engagement inhibits Th2 but not Th1 cell polarisation.
AB  - CTLA-4 deficient mice show severe lymphoproliferative disorders with T helper sub
      population skewed toward the Th2 phenotype. In the present work, we investigated
      the role of CTLA-4 in T helper cell subset differentiation. Naive CD4+ cells were
      stimulated with anti-CD3 and anti-CD28 mAbs in the presence of either IL-12 or IL
      4 to induce polarisation to Th1 or Th2 cells, respectively. Under these two
      polarising conditions cells express comparable levels of CTLA-4. CTLA4 was
      stimulated by plastic-bound mAb. The frequency of IFN-gamma- and IL-4-producing
      cells were estimated by FACS analysis. In parallel cultures, polarised Th1 and
      Th2 cells were re-stimulated with anti-CD3 and anti-CD28 mAbs for 48 h and their
      culture supernatants analysed by ELISA. Results show that CTLA-4 engagement
      during differentiation inhibits polarisation of naive CD4+ cells to the Th2 but
      not the Th1 cell subset. At variance, once cells are polarised, CTLA-4 engagement
      inhibits cytokine production in both effector Th2 and Th1 cells. Altogether these
      data indicate that CTLA-4 may interfere not only in the signalling involved in
      acute transcriptional activation of both Th1 and Th2 cells but also in the
      development of one of the Th cell subsets.

PMID- 14575156
TI  - Second-hand smoke increases bronchial hyperreactivity and eosinophilia in a
      murine model of allergic aspergillosis.
AB  - Involuntary inhalation of tobacco smoke has been shown to aggravate the allergic
      response. Antibodies to fungal antigens such as Aspergillus fumigatus (Af) cause
      an allergic lung disease in humans. This study was carried out to determine the
      effect of environmental tobacco smoke (ETS) on a murine model of allergic
      bronchopulmonary aspergillosis (ABPA). BALB/c mice were exposed to aged and
      diluted sidestream cigarette smoke to simulate 'second-hand smoke'. The
      concentration was consistent with that achieved in enclosed public areas or
      households where multiple people smoke. During exposure, mice were sensitized to
      Af antigen intranasally. Mice that were sensitized to Af antigen and exposed to
      ETS developed significantly greater airway hyperreactivity than did mice
      similarly sensitized to Af but housed in ambient air. The effective concentration
      of aerosolized acetylcholine needed to double pulmonary flow resistance was
      significantly lower in Af + ETS mice compared to the Af + AIR mice. Immunological
      data that supports this exacerbation of airway hyperresponsiveness being mediated
      by an enhanced type 1 hypersensitivity response include: eosinophilia in
      peripheral blood and lung sections. All Af sensitized mice produced elevated
      levels of IL4, IL5 and IL10 but no IFN-gamma indicating a polarized Th2 response.
      Thus, ETS can cause exacerbation of asthma in ABPA as demonstrated by functional
      airway hyperresponsiveness and elevated levels of blood eosinophilia.

PMID- 14575155
TI  - Characterization of vascular adhesion molecules that may facilitate progenitor
      homing in the post-natal mouse thymus.
AB  - T cell progenitors derive from the bone marrow but must migrate via bloodstream
      to the thymus in order to differentiate. The mechanism by which the thymus
      recruits progenitors from the blood is unknown. It is known, however, that there
      are receptive and refractory periods for progenitor recruitment and that when
      cells are imported, they enter the thymus through post-capillary venules.
      Therefore, recruitment is an active process temporally and spatially regulated.
      In order to characterize the mechanism of recruitment, we evaluated vascular
      signals known to regulate leukocyte extravasation, with respect to their
      intrathymic location and temporal fluctuations. We find that CD34, MECA79, VCAM
      1, ICAM-1 and VAP-1 are all expressed in thymic blood vessels. MECA79 and VAP-1
      appear to be specific for post-capillary venules, while ICAM-1 and VCAM-1 are
      also found on intrathymic stromal cells. MAdCAM is also expressed in the thymus,
      but is not associated with vascular tissues. Only MECA79 is upregulated during
      recruitment peaks, suggesting a role for this molecule in the periodicity of
      recruitment. Together, these studies reveal potential roles for L-selectin
      ligands, VCAM-1, ICAM-1 and VAP-1 in progenitor recruitment to the thymus, and
      implicate the presence of other periodic signals, such as chemokines and
      cytokines, that cooperate to execute this essential function.

PMID- 14575157
TI  - The primary responses of murine neonatal lymph node CD4+ cells are Th2-skewed and
      are sufficient for the development of Th2-biased memory.
AB  - Exposure of neonatal mice to antigen often results in Th2-biased responses in
      later life. Examples of this Th2 tendency are (a) secondary antibody responses
      dominated by the Th2-associated IgG1 isotype and (b) Th2-mediated tolerance to
      alloantigens. We previously reported that neonates develop primary Th1 and Th2
      function in the lymph nodes but exclusive Th2 primary splenic responses. Here, we
      have tested whether the Th2 bias of adults initially immunized as neonates is due
      to the early, primary Th2 polarization in the spleen. Surprisingly, removal of
      the spleen at birth had no affect on either IgG1-dominant secondary responses or
      the development of tolerance to alloantigens. Thus, neonatal lymph nodes are
      sufficient to generate Th2-biased function following neonatal antigen exposure.
      To understand how this could arise, we examined the primary Th1/Th2 responses of
      CD4+ lymph node cells. Unlike the balanced Th1/Th2 responses seen with total
      lymph node cells, the primary responses of isolated CD4+ cells were skewed to IL
      4 producing function. These results suggest that the early development of Th2
      dominant responses by lymph node CD4+ cells contributes substantially to the
      subsequent development of Th2-dominant memory in neonates.

PMID- 14575158
TI  - Essential microenvironment for thymopoiesis is preserved in human adult and aged
      thymus.
AB  - Normal human thymuses at various ages were immunohistologically examined in order
      to determine whether adult or aged thymus maintained the microenvironment for the
      T cell development and thymopoiesis was really ongoing. To analyze the thymic
      microenvironment, two monoclonal antibodies (MoAb) were employed. One is MoAb to
      IL-1 receptor (IL-1R) recognizing medullary and subcapsular cortical epithelial
      cells of normal infant human thymus. The other is UH-1 MoAb recognizing thymic
      epithelial cells within the cortex, which are negative with IL-1R-MoAb. Thymus of
      subjects over 20 years of age was split into many fragments and dispersed in the
      fatty tissue. However, the microenvironment of each fragment was composed of both
      IL-1R positive and UH-1 positive epithelial cells, and the UH-1 positive portion
      was populated with lymphocytes showing a follicle-like appearance. Lymphocytes in
      these follicle-like portions were mostly CD4+CD8+ double positive cells and
      contained many proliferating cells as well as apoptotic cells. Thus these
      follicle-like portions in adult and aged thymus were considered to be functioning
      as cortex as in infant thymus. Proliferative activity of thymocytes in the thymic
      cortex and the follicle-like portions definitely declined with advance of age,
      while incidence of apoptotic thymocytes increased with aging.

PMID- 14575159
TI  - Both maturation and survival of human dendritic cells are impaired in the
      presence of anergic/suppressor T cells.
AB  - T cell suppression is a well established phenomenon, but the mechanisms involved
      are still a matter of debate. Mouse anergic T cells were shown to suppress
      responder T cell activation by inhibiting the antigen presenting function of DC.
      In the present work we studied the effects of co-culturing human anergic CD4+ T
      cells with autologous dendritic cells (DC) at different stages of maturation.
      Either DC maturation or survival, depending on whether immature or mature DC
      where used as APC, was impaired in the presence of anergic cells. Indeed, MHC and
      costimulatory molecule up-regulation was inhibited in immature DC, whereas
      apoptotic phenomena were favored in mature DC and consequently in responder T
      cells. Defective ligation of CD40 by CD40L (CD154) was responsible for CD95
      mediated and spontaneous apoptosis of DC as well as for a failure of their
      maturation process. These findings indicate that lack of activation of CD40 on DC
      by CD40L-defective anergic cells might be the primary event involved in T cell
      suppression and support the role of CD40 signaling in regulating both activation
      and survival of DC.

PMID- 14575160
TI  - The role and importance of farriery in equine veterinary practice.
AB  - There is a lot of room for us to become the central source of medical information
      regarding shoeing and lameness in our own practice area. This takes a good bit of
      effort and a real "outreach" to client and farrier. It can be done with the one
      tool we are best at--the acquisition and careful dispensing of information that
      we can put together regarding the health of the foot. Such information includes
      the following: 1. Radiographically guided hoof trimming and shoeing. 2.
      Ultrasonography. 3. Digital radiography. 4. Thermography. 5. Nutritional and
      health counseling. Become the "local" expert in hoof health and farrier science.
      Publish a newsletter on the subject, and speak to small groups clients.
      Participate in farrier education at both the national and local level. Attend
      and/or speak at farrier symposiums. Do not be intimidated by the Internet. We
      have more "gurus" than they do. Tap into the stream of educational materials
      available, such as journals, videotapes, and colleague recommendations. Realize
      that you do not have to convince a national audience of your knowledge; the one
      client in front of you at the time is plenty. Take time to talk to farriers;
      discuss your ideas based on fact or clinical experience rather than dictating
      your thoughts, and do not lecture them unless you have a tray full of slides.
      Give them a goal rather than a prescription engraved on a stone tablet (ie, "we'd
      like to see this horse grow a little more heel"). Let them "choose" how to
      accomplish your goal. It is a good idea to be respectful in all discussions with
      people who carry hammers and bend iron for a living. All of us need to realize
      that there are probably more horses in the world today that spend their entire
      working lives unshod and without the benefit of our combined expertise. There is
      little doubt that they would be better off with our help in many instances, but
      the fact remains that many lead long productive lives unshod. This fact can lead
      to some confusion among many clients who suddenly ask for a "'mustang" trim or
      others who advocate a return to "natural" trims, not ever realizing that we have
      changed all the natural patterns of their horses' lives and physiology by
      introducing confinement, artificial bedding, weight bearing, and artificial
      diets, altering hoof growth in the process. Shoeing, hoof care, and hoof repair
      become necessary in many situations of domestication. We need to be skilled in
      assessing the appropriateness and quality of the shoes and technology used and
      thus help in the adaptation to demands placed on our equine patients. Conversely,
      we can use the principles of the natural trim and apply them to the foot as shown
      in Figs. 1 and 2 (Fig. 6). One must be aware of the latest in shoeing "fads" and
      realize that although certain shoes are suddenly popular because they solve one
      type of lameness, they are not always a substitute for tried and true methods
      (Fig. 7). Become familiar with the options, and work within the confines of your
      knowledge and with the assistance of a competent farrier.

PMID- 14575161
TI  - Form and function of the equine digit.
AB  - The list of possible diagnoses derived from matching anatomic structures or
      tissues to pathologic processes is inevitably broad in nature. Understanding and
      observation of distal limb function, conformation, and balance is the basis of
      identifying where the greatest abnormal stresses within the distal limb are
      likely to occur. This is key to focusing the diagnostic process and, in some
      instances, to treating the horse when a definitive diagnosis cannot be achieved.

PMID- 14575163
TI  - Proper physiologic horseshoeing.
AB  - Adherence to the basic principles of physiologic horseshoeing is essential to
      maintaining hoof health and soundness. Most horses do not require special
      trimming or shoeing techniques. Becoming familiar with a few basic concepts can
      help the veterinarian to recognize when changes in trimming or shoeing might be
      expected to help the performance of a sound horse or might help to restore the
      performance of one that is lame. Sound physiologic horseshoeing can only be
      achieved by a thorough knowledge of, strict adherence to, and skillful
      application of basic principles, such as hoof angle, HPA, and mediolateral
      balance. Only then does the art of farriery truly approach being a science.

PMID- 14575162
TI  - Examination of the equine foot.
AB  - The examination of the foot must be based on observations of the hoof, followed
      by a careful determination of areas of pain. This must be followed by an
      assessment of the biomechanical forces on the hoof and limb. Finally, imaging
      gives insight into the nature of the injury and allows the examiner to
      prognosticate the outcome.

PMID- 14575164
TI  - Natural balance trimming and shoeing: its theory and application.
AB  - The principles and techniques of natural balance trimming and shoeing are
      designed to optimize the efficiency and function of the foot. The basic
      guidelines have evolved in part from wild horse hoof imprint studies done in 1986
      through 1987 and first presented in 1995. Further research has contributed to
      these principles and guidelines to make them applicable to domestic horses.

PMID- 14575165
TI  - Radiographic imaging of the equine foot.
AB  - Radiographic examination of the equine foot can provide the veterinarian and
      farrier with a wealth of information. Positioning and selection of exposure
      factors are of central importance if one is to produce radiographs of maximum
      diagnostic value.

PMID- 14575166
TI  - Chronic laminitis: current treatment strategies.
AB  - Laminitis is divided into four different phases: developmental, acute, subacute,
      and chronic. The focus of this article is on treating the laminitic horse after
      the cessation of therapy for the acute phase, that is, usually 2 to 4 weeks after
      the onset of clinical signs.

PMID- 14575167
TI  - Diagnosis, treatment, and farriery for horses with chronic heel pain.
AB  - In conclusion, horses with heel or navicular area pain vary, and no one treatment
      option is suitable for all horses. Each horse must be evaluated individually to
      determine which structure in the palmar aspect of the foot is injured, severity
      of disease, horse and hoof conformation, and horse use and level of performance
      expectation before a treatment plan can be developed. Overall, there are many
      treatment options to help these horses to perform their intended athletic event.

PMID- 14575168
TI  - Hoof capsule distortion: understanding the mechanisms as a basis for rational
      management.
AB  - Understanding the basic mechanisms of hoof capsule distortion enables the
      clinician to unravel the sometimes complex mix of abnormalities, identify early
      warning signs, and manage existing problems more effectively. Distortion of the
      hoof capsule can often seem like a complicated puzzle by the time the
      veterinarian is called to examine the lame horse. Evaluating each of the
      components of the hoof capsule, both individually and as an integrated unit,
      allows the clinician to tease apart the tangle of primary and secondary problems
      and come up with effective options for countering or attenuating the forces
      responsible for the distortion. Using high-quality radiography and developing an
      eye for detail regarding the physical and radiographic characteristics of the
      foot allow the clinician to identify subtle abnormalities, thereby averting a
      clinical problem or addressing the problem while it is still reversible. With
      existing problems, developing these skills enhances the clinician's ability to
      interpret the degree of damage accurately and to devise mechanical solutions that
      create an environment in which healing and restoration of function are maximized.

PMID- 14575170
TI  - Hoof wall surgery in the horse: approaches to and underlying disorders.
AB  - Because of the hoof capsule, surgery of the equine foot is often perceived to be
      quite difficult. Knowledge of the specific disease entities that require surgical
      intervention as well as an in-depth understanding of the anatomy of the tissues
      beneath the hoof capsule is a definite prerequisite to successful surgical
      treatment. This article details the surgical approaches used to treat septic
      navicular bursitis, septic pedal osteitis, infection of the collateral
      cartilages, and keratomas. The principles used to treat these conditions can be
      applied to a variety of other conditions for which access through the hoof wall
      is required.

PMID- 14575169
TI  - Hoof wall defects: chronic hoof wall separations and hoof wall cracks.
AB  - Hoof wall defects in horses are common occurrences, and, fortunately, many of
      those detected present little or no danger to the individual horse. Those defects
      that are either presently a problem or have a great likelihood of being a problem
      do often require specialized consideration. Horse shoeing and farriery are
      ancient practices; over the years, a multitude of methods, theories, and
      management schemes have been proposed. It is unfortunate to note that few studies
      are available to provide an accurate incidence rate, a better understanding of
      the various causes, and, lastly, a comparative appreciation of the possible modes
      of treatment and management. This discussion reflects the thinking and experience
      of the author and, as such, should be read and viewed with an open and critical
      mind set.

PMID- 14575171
TI  - Foot management in the foal and weanling.
AB  - Foot management and hoof care of foals, weanlings, and yearlings tends to be
      considered a specialist job. Many farriers and veterinary surgeons have little
      exposure to young and growing stock. Nevertheless, a variety of angular and
      flexural limb deformities can benefit from simple podiatry techniques, which can
      be performed provided that a few basic rules are followed. The combined skills of
      the farrier and veterinary surgeon offer many young horses with angular or
      flexural limb deformities a chance of a future athletic career.

PMID- 14575172
TI  - Hoof repair and glue-on shoe adhesive technology.
AB  - There are many different commercially available hoof repair/adhesive products.
      The application of these products in the treatment of various foot conditions is
      continuing to evolve based on sound medical and farriery principles as well as
      imagination. Successful application of these products depends largely on using
      proper hoof wall preparation and adhesive application techniques. Success also
      depends on a realistic expectation of the final outcome when accounting for the
      physical limitations of the adhesive products and the underlying hoof problem.
      Our results with these techniques have been encouraging and rewarding.

PMID- 14575173
TI  - Foot pain and the elusive diagnosis.
AB  - New information about foot anatomy, effects of local analgesia, and advances in
      diagnostic imaging (ultrasonography, nuclear scintigraphy, MRI, CT, and
      endoscopy) has opened the way for more specific diagnoses of lameness. New
      questions have been raised, however, and some older ideas are now in doubt. This
      article discusses some of these findings in the light of our own clinical
      experiences as they relate to diagnosis of the causes of foot pain.

PMID- 14575175
TI  - A long-term study on vector abundance & seasonal prevalence in relation to the
      occurrence of Japanese encephalitis in Gorakhpur district, Uttar Pradesh.
AB  - BACKGROUND & OBJECTIVES: Japanese encephalitis (JE) virus is an important cause
      of viral encephalitis in Gorakhpur district, UP. The area has been experiencing
      outbreaks of JE since 1978. No in-depth longitudinal studies have been carried
      out on the mosquito species, particularly JE vectors prevailing in the area.
      Entomological studies were carried out in the district in order to determine the
      species composition, relative abundance and seasonal prevalence of mosquitoes in
      relation to the incidence of JE. METHODS: Three JE affected villages were
      selected as study sites. Weekly visits were made to each village and mosquito
      collections were made in and around the pig enclosures and cattle sheds with the
      help of mouth aspirators, aided by flash lights at dusk. RESULTS: The overall
      mosquito population showed a bimodal pattern with short and tall peaks during
      March and September respectively. Based on the elevated density and infection
      with JE virus, Culex tritaeniorhynchus has been considered responsible for
      causing epidemics in the area. Cx. pseudovishnui, Cx. whitmorei, Cx. gelidus, Cx.
      epidesmus, Anopheles subpictus, An. peditaeniatus and Mansonia uniformis are
      suspected to have played some role in the epidemiology of JE in the region. JE
      cases were reported between August and November with the peak in October when the
      vectors population, particularly Cx. tritaeniorhynchus was on the decline.
      INTERPRETATION & CONCLUSION: The results of the study indicate that Cx.
      tritaeniorhynchus, the most likely vector of JE together with other known vector
      species remained more active during the period of paddy cultivation. Integrated
      antilarval measures before the beginning of paddy irrigation may check the
      breeding of JE vectors in the paddy fields. It may prove beneficial in reducing
      the vector population during the JE transmission season.

PMID- 14575174
TI  - Cytomegalovirus co-infection in patients with HIV/AIDS in north India.
AB  - BACKGROUND & OBJECTIVES: Cytomegalovirus (CMV) is a frequent opportunistic
      infection in immunocompromised individuals particularly those receiving organ
      transplants and harbouring HIV infection. The classical CMV syndrome may be seen
      in only a small percentage of patients and tissue diagnosis is cumbersome, costly
      and requires hospitalization. Hence there is an urgent need to establish accurate
      and early diagnosis for proper institution of therapy. An attempt was made to
      detect active CMV co-infection in patients with HIV/AIDS using three assays and
      the positivity rates in the 2 groups compared. METHODS: In the present study, we
      used a highly sensitive polymerase chain reaction (PCR) for immediate early gene
      of CMV, pp65 antigenaemia assay and IgM ELISA assay to detect the presence of CMV
      co-infection in 37 patients with AIDS and 32 healthy HIV seropositives. Thirty
      healthy laboratory workers served as normal controls. RESULTS: Of the 37 patients
      with AIDS, 12 (32.4%) showed a positive reaction by PCR and only 4 patients were
      positive by the antigenaemia assay. Of the 32 HIV seropositives, only one was
      positive by PCR (3%), and all were negative for antigen assay. None of the
      controls showed positivity by any of the tests. The difference in PCR positivity
      rates between HIV seropositives and patients with AIDS was significant (P < 01).
      IgM antibodies were positive in four (10.3%) AIDS patients and only one (3%) HIV
      seropositive, the difference was insignificant. The difference in antigen
      positivity between IIIV seropositives and AIDS patients was also insignificant.
      INTERPRETATION & CONCLUSION: CMV appears to be an important co-infection in
      patients with AIDS in India and PCR is a powerful tool for detection of CMV in
      blood and is superior to the antigenaemia assay. PCR can be performed with a
      small volume of blood avoiding any invasive procedure, and can provide quick
      information for timely institution of therapy.

PMID- 14575176
TI  - Comparative evaluation of protective antigen produced from Bacillus anthracis &
      Escherichia coli.
AB  - BACKGROUND & OBJECTIVE: Anthrax has been reported from almost every country and
      India is endemic for this disease. There is considerable under reporting of the
      disease because of lack of microbiological facilities and diagnostic reagents. In
      India only conventional methods which have limitations, are being used to
      diagnose the disease. Hence the aim of this study was to isolate and purify
      protective antigen (PA) using different protocols and to use this PA for
      detection of anti-PA antibodies from sera samples. METHODS: Protective antigen
      was isolated and purified from the Sterne strain of Bacillus anthracis. B.
      anthracis lacking pXO1 and pXO2 transformed with pYS5 (B. anthracis pYS5) and
      recombinant Escherichia coli transformed with pQE30 containing PA gene using
      hydroxyapatite (HA), Q-sepharose fast protein liquid chromatography (FPLC) and
      nickel-nitrilotriacetic acid (Ni-NTA) chromatographic methods, respectively. A
      mixture of PA and edema factor (EF) was injected subcutaneously into rabbits to
      test the biological activity of PA. The immunogenicity of PA was tested by
      inoculating the protein into rabbits along with adjuvant. Using this PA, 20
      bovine sera samples (pre- and post-vaccinated) were tested by Western blotting
      (WB) for the presence of anti-PA antibodies. RESULTS: The 83 kDa PA protein was
      obtained from all the bacteria with the yields of 13, 50 and 9.0 mg/l from Sterne
      B. anthracis, B. anthracis pYS5 and recombinant Esch. coli, respectively.
      Formation of edematous ulcers at the site of PA+EF injection clearly confirmed
      the retention of biological activity of the proteins. Of the 10 post-vaccination
      sera tested, 9 showed clear positive by WB whereas none of the pre-vaccination
      sera showed the reaction. INTERPRETATION & CONCLUSION: The purified PA
      preparations obtained in the present study may possibly be utilized for detection
      of anti-PA antibodies in the sera of anthrax patients for timely diagnosis of the
      disease and, might also be tested for their efficacy and use as human anthrax
      vaccine.

PMID- 14575177
TI  - Septicaemic melioidosis in a tertiary care hospital in south India.
AB  - BACKGROUND & OBJECTIVES: Melioidosis and the causative organism Burkholderia
      pseudomallei are being recognized gradually in various centres in India. In the
      septicaemic form, melioidosis is a serious and life threatening condition which
      requires early detection and specific treatment to avoid case fatality. A review
      of patients with septicaemic melioidosis at a tertiary care hospital in south
      India was carried out with a view to define the clinical features, predisposing
      conditions, if any, and the outcome. METHODS: A total of 28 patients with culture
      proven septicaemic melioidosis during December 1993 to December 2002 were
      included. Information on clinical details and outcome was obtained and antibiotic
      susceptibility of the isolates studied. RESULTS: Of the 28 patients of blood
      culture proven septicaemic melioidosis, the organism was also isolated from pus
      in two patients. The presenting clinical features were varied, most presenting as
      pyrexia of unknown origin or visceral abscesses, or septic arthiritis.
      Associated/predisposing conditions were present in 50 per cent of the patients,
      and diabetes mellitus was the commonest one. mortality was 58 per cent in our
      series. INTERPRETATION & CONCLUSION: Melioidosis is an emerging infection in
      India. The magnitude of the problem can only be assessed by increasing awareness,
      both of its existence in the clinical setting and its identification in the
      laboratory.

PMID- 14575178
TI  - Candidaemia in patients of a tertiary health care hospital from north India.
AB  - BACKGROUND & OBJECTIVES: Candidaemia is an important cause of mortality in
      hospital settings. Limited information is available from India on nosocomial
      candidaemia. The objective of the present study was to isolate and identify
      yeasts from patients suspected to have nosocomial bloodstream infection (BSI) and
      to determine the carriage rate of Candida species, risk factors for acquisition
      of infection and mortality in this group of patients. METHODS: Blood samples from
      4871 patients suspected to have BSI at least 48 h after admission were cultured
      following standard protocol to isolate and identify the pathogens. Clinical
      details, possible risk factors and outcome of all candidaemic patients were
      recorded and analysed. Samples of hand washings and throat gargles from these
      patients were also cultured to determine the carriage rate. Candida albicans
      isolated from patients and their carriage sites were genotyped by randomly
      amplified polymorphic DNA (RAPD) analysis to study strain relatedness. RESULTS:
      Twenty one patients with candidaemia were detected with mortality of 55 per cent.
      Candidaemia per 1000 admissions was 1.61. Isolation of non-C. albicans Candida
      species was significantly higher than C. albicans (14/21 vs 7/21: P < 0.05). Use
      of broad-spectrum antibiotics (43%), gastrointestinal surgery (23%),
      immunosuppressive therapy (23%), protein calorie malnutrition with parenteral
      hyperalimentation (23%) and neutropaenia (14%) were identified as probable risk
      factors. The seven C. albicans strains isolated from patients with BSI were typed
      into 6 genotypes. Yeast carriage rate among the patients was 71.4 per cent. C.
      albicans isolated from the hand, throat and blood of two patients had identical
      genotype. INTERPRETATION & CONCLUSION: BSI due to non-C. albicans Candida species
      is more common than C. albicans in our patients and candidaemia is associated
      with high mortality. RAPD appears to be a simple method to study strain
      relatedness for C. albicans. There is a need for early diagnosis and systematic
      surveillance to meet the challenges of nosocomial candidaemia.

PMID- 14575179
TI  - Surfactant protein-A levels in patients with acute respiratory distress syndrome.
AB  - BACKGROUND & OBJECTIVES: The decrease in surfactant protein-A (SP-A level) has
      recently been implicated in the pathophysiology of acute respiratory distress
      syndrome (ARDS). Mechanical ventilation is the main modality of treatment of
      ARDS. But information on the SP-A levels after mechanical ventilation is scanty.
      We therefore studied the effect of mechanical ventilation on SP-A levels in
      patients with ARDS. METHODS: In a prospective, observational study conducted in
      the Respiratory Intensive Care Unit of a tertiary care hospital in north India,
      13 patients with ARDS requiring mechanical ventilation were included. SP-A levels
      in the bronchial aspirates were serially estimated by ELISA at the start of
      mechanical ventilation and after 24 and after 48 h. RESULTS: The SP-A level at
      the start of mechanical ventilation was 3.06 +/- 2.56 microg/ml. The levels
      gradually increased to 3.99 +/- 2.39 and 6.64 +/- 2.72 microg/ml, at 24 and 48 h
      respectively, and this increase was statistically significant (P < 0.05).
      Patients having an infectious etiology had lower SP-A levels compared to those
      with non-infections causes. Neither the initial SP-A level nor the increase in SP
      A level correlated with the improvement in lung function or duration of
      ventilation. INTERPRETATION & CONCLUSION: The present study showed a progressive
      increase in the SP-A levels in patients with ARDS on mechanical ventilation.
      Further studies are required to confirm that the increase in SP-A levels may be
      one of the contributors for recovery in ARDS.

PMID- 14575180
TI  - Lack of sleep another safety risk factor.

PMID- 14575181
TI  - Bipolar transurethral resection.

PMID- 14575182
TI  - Maintaining the chain of custody--evidence handling in forensic cases.
AB  - IN VIOLENCE AND ABUSE CASES, perioperative nurses are responsible for protecting
      victims' rights and ensuring that potential evidence of a crime is not
      compromised. FORMAL EDUCATION for nurses now is available in the relatively new
      field of clinical forensic nursing. PERIOPERATIVE NURSES should ensure that they
      receive proper education in identifying, collecting and securing evidence and
      maintaining the chain of custody, whether through a formal education process or
      by reviewing protocols at their facilities.

PMID- 14575183
TI  - Basic electrocardiogram interpretation for perioperative nurses.
AB  - CHANGES IN PRACTICE have made knowledge of the cardiac conduction system and
      basic electrocardiogram (EKG) interpretation a necessity because perioperative
      nurses are required to manage an increasing number of patients undergoing i.v.
      conscious sedation who require EKG monitoring. RAPID EKG INTERPRETATION can
      reveal arrhythmias before a patient becomes symptomatic. An EKG can reveal
      underlying cardiac problems and uncover electrolyte imbalances that, if left
      untreated, could hinder positive patient outcomes. THE CONDUCTION AND CORONARY
      ARTERY SYSTEMS of the heart are described to enable identification of normal and
      abnormal EKG rhythms. Each arrhythmia is described, and potential causes and
      probable treatments are discussed.

PMID- 14575184
TI  - Accommodating latex allergy concerns in surgical settings.
AB  - CONCERN ABOUT ALLERGIC REACTIONS to natural rubber latex gloves has increased
      during the past 15 years. These reactions have been attributed mainly to an
      influx of high-powder, high-protein gloves in response to increasing concerns
      about AIDS transmission beginning in the late 1980s. THIS ARTICLE REPORTS ON
      AVAILABLE RESEARCH that details the types and prevalence of potential allergic
      reactions, supports the use of natural rubber latex gloves in the OR, and
      recommends strategies to enable health care who are not latex sensitive to
      continue wearing natural rubber latex gloves in the OR.

PMID- 14575185
TI  - Preadmission testing in a children's facility.
AB  - NURSES IN A SAME DAY SURGERY (SDS) UNIT used their hospital's quality model to
      identify a long-term problem, establish a project, analyze the problem, and make
      recommendations for changes to improve patient care. THE PROCESS included
      conducting a review of the literature, collecting data about procedure delays and
      cancellations, making a site visit to another children's hospital, and presenting
      pertinent findings to the OR committee. THE NURSES initiated a pilot program to
      bring surgical patients into the SDS area for a preadmission testing visit.
      DELAYS AND CANCELLATIONS decreased, and satisfaction among nurses working in the
      SDS unit increased as a result of this program.

PMID- 14575186
TI  - From hand maiden to right hand--the birth of nursing in America.
AB  - AT THE ONSET of the American Civil War, women were asked to leave their homes and
      serve as suppliers and caregivers for the armies on both sides of the conflict.
      MANY WOMEN suddenly found themselves in situations that required real strength,
      stamina, and fortitude, and some found an inner strength as they organized others
      to provide care. WOMEN LIKE Dorthea Dix and Clara Barton were among the first to
      champion the ability of and the need for women to provide nursing care, which
      until then had been a male bastion. THIS ARTICLE, which is the second in a two
      part series on nursing during the Civil War, tells how Dorthea Dix, Clara Barton,
      and other women worked to establish nursing as a viable career choice for women
      in the United States.

PMID- 14575187
TI  - The experience of being an older perioperative nurse.
AB  - THIS QUALITATIVE STUDY used a purposive sample of perioperative nurses age 50 or
      older to describe the experience of being an older perioperative nurse. Three
      themes were identified from data analysis: growing old in the OR, inter-personal
      and organizational concerns, and worries about the future. THESE OLDER
      PERIOPERATIVE NURSES still are challenged and energized by being in the OR,
      although they have concerns about call and scheduling and have experienced
      conflict with surgical technologists. THESE NURSES ALSO ARE VERY WORRIED about
      the future of nursing, specifically perioperative nursing. They aptly asked,
      "What's going to happen when the older nurses are gone and no one is here to
      train the new ones?"

PMID- 14575188
TI  - Schedule the short procedure first to improve OR efficiency.
AB  - OPERATING ROOM MANAGERS are hampered in their efforts to optimize OR efficiency
      by surgical procedures that last a longer or shorter time than scheduled. The
      lack of predictability is a result of inaccuracy in scheduling and variability in
      the duration of procedures. SCHEDULING SHORT PROCEDURES before long procedures
      theoretically limits this variability. MONTE CARLO SIMULATION of ORs scheduled
      with various combinations of short and long procedures supports this concept's
      validity. RESULTS INDICATE that scheduling short procedures first can improve on
      time performance and decrease staff member overtime expense without reducing
      surgical throughput.

PMID- 14575189
TI  - Preventing fires in the OR.

PMID- 14575190
TI  - Patient safety legislation.

PMID- 14575191
TI  - Research publication in developing countries.

PMID- 14575192
TI  - Leisure time physical activity and coronary heart disease mortality in men
      symptomatic or asymptomatic for ischaemia: evidence from the Whitehall study.
AB  - BACKGROUND: Although numerous studies have shown an association between physical
      activity and coronary heart disease (CHD) mortality in healthy persons, few have
      reported on this relation in individuals with pre-existing diseases, such as
      ischaemia. Further, we are unaware of any study to examine if this relationship
      is modified by the symptomatic nature of the ischaemia. METHODS: To explore these
      issues, we analysed data from a 25 year follow-up of mortality for 6474 male
      British civil servants who underwent a resting electrocardiogram and responded to
      queries regarding angina at study entry. RESULTS: Among men who had ECG
      abnormalities but no angina (i.e. asymptomatic), activity was associated with a
      higher rate of CHD mortality. Among men with both angina and ECG abnormalities
      (i.e. symptomatic), activity was associated with lower CHD mortality but this was
      not statistically significant at conventional levels. CONCLUSIONS: In the present
      study, there was a suggestion that the symptomatic nature of ischaemia appeared
      to modify the effect of physical activity on total and CHD mortality. Although
      these findings should be examined in other studies, they point to the need for a
      pre-participation medical examination in active persons or those contemplating
      embarking on an activity programme.

PMID- 14575193
TI  - Properties of the Picker Patient Experience questionnaire in a randomized
      controlled trial of long versus short form survey instruments.
AB  - BACKGROUND: The purpose of this study was to compare the performance of the 15
      item Picker Patient Experience questionnaire (PPE-15) when embedded in a short
      form instrument as compared with a longer form measure. METHODS: A postal
      questionnaire survey of patients recently discharged from two hospital trusts was
      carried out. Patients were randomized to receive the PPE-15 in either a four-page
      or a 12-page survey instrument. RESULTS: A total of 1445 questionnaires were
      mailed to patients in either four- or 12-page formats. A total of 949 (65.67 per
      cent) forms were returned. No difference in response rate was found between the
      two versions of the questionnaire. Item completion and psychometric properties of
      the PPE-15 were not found to differ significantly between the two arms of the
      trial. CONCLUSION: In this survey the length of questionnaire in which the PPE-15
      was embedded had no impact in terms of response rate or data quality.
      Consequently, the results suggest that length of questionnaire, up to the 108
      items included in the 12-page survey, is unlikely to adversely affect results on
      the PPE-15.

PMID- 14575194
TI  - Addressing the inverse care law in cardiac services.
AB  - BACKGROUND: Wide variation in rates of angiography and revascularization exist
      that are not explained by the level of need for these services. The National
      Service Framework for Coronary Heart Disease has set out a number of standards
      with the aim of increasing the number of revascularizations and reducing
      inequalities in access to care. In this study we aimed to investigate inequity in
      angiography and revascularization rates between the four Primary Care Group (PCG)
      areas in Camden and Islington Health Authority and to put in place measures to
      address the problems identified. METHODS: Routinely available data were collected
      on all residents within Camden and Islington Health Authority undergoing
      angiography, angioplasty (PTCA) or coronary artery bypass grafting (CABG) between
      1997 and 2001. These were used to calculate intervention rates per million
      population for each of the three procedures within each PCG. Semi-structured
      interviews were carried out with a sample of clinicians to explore their views on
      the provision of revascularization services within the Health Authority. RESULTS:
      Angiography and revascularization rates varied widely between the four PCGs. In
      2001 there was a two-fold difference for angiography and CABG and a 3.5-fold
      difference for PTCA. The variations were not explained by a measure of the level
      of need for these services. The highest rates were in the area with the lowest
      standardized mortality ratio for coronary heart disease. The interviews
      identified a number of possible explanations for the variations that related to
      differences in clinical behaviour atthe consultant level and barriers in access
      to interventional cardiology and cardiac services. Following this research, a
      further interventional cardiologist appointment is planned, joint protocols of
      care are being established and barriers to access are being addressed.
      CONCLUSIONS: The new strategic health authorities should make it a priority to
      assess inequity in the provision of services within their areas, investigate the
      possible causes and support the primary care trusts to implement plans to address
      them.

PMID- 14575195
TI  - Are socioeconomic inequalities in mortality decreasing or increasing within some
      British regions? An observational study, 1990-1998.
AB  - BACKGROUND: This paper evaluates claims in a recent study that inequalities in
      small area mortality rates have lessened. We examine the effect of differently
      estimated populations on time trends in age-specific mortality rates for
      Yorkshire and the Humber and East of England. METHODS: Populations were estimated
      for wards using four methods that introduce increasing amounts of information.
      Age-specific mortality rates for age-groups 45-54, 55-64, 65-74 and 75-84 for
      both sexes were calculated for population-weighted deprivation quintiles.
      Inequality was tracked using ratios of rates in the most deprived quintile
      divided bythose in the least. RESULTS: When constant 1991 populations are used,
      rate ratios decrease for all age-sex groups, indicating shrinking inequality.
      When a method adjusting small area populations to official district estimates is
      used, both decreases and increases are observed in the mortality rate ratios.
      These results differ from Trent region findings of decreases in inequality. When
      small area populations are cohort-survived and adjusted to district populations,
      most differences in rate ratios indicate increasing inequality. When a method is
      used that includes information on migration and special populations, then seven
      out of eight age-sex groups exhibit increasing inequality. CONCLUSIONS: A
      judgement about trends in mortality inequality is highly dependent upon the
      denominator population used. Simpler estimation methods result in convergence of
      rate ratios, whereas more sophisticated methods result in increasing inequalities
      in most age-sex groups.

PMID- 14575196
TI  - Making sense of symptom checklists: a latent class approach to the first 9 years
      of the British Household Panel Survey.
AB  - BACKGROUND: In health inequalities research there is a growing impetus to examine
      the development of inequalities in health over time. However, many of the sources
      of longitudinal data in Britain are not designed specifically for health
      research. Typically, health status is assessed by self-reported problems and the
      use of symptom checklists. METHODS: The British Household Panel Survey (BHPS) is
      an annual survey of approximately 5500 private households containing 9000 men and
      women, which began in 1991. Each year, the BHPS contains a checklist of 13 health
      problems and symptoms. The findings presented here are based on adult
      participants aged 16 years and over in 1991. Using eight waves of data from the
      BHPS, we use latent class analysis (LCA) to model latent health status from a set
      of observed binary variables. Individuals are assigned to a latent health class
      on the basis of LCA estimated probabilities of class membership given their
      response patterns and the estimated unconditional class frequencies. The
      predictive value of latent health class membership is assessed for self-reported
      health status and functioning, health and welfare service use, and mortality 1
      year later. RESULTS: The LCA supported a suitable four-class model of health
      status representing good health, psychosomatic health problems, physical health
      problems and comorbid health problems. Members of the good latent health class
      were predicted to have better self-reported health and functioning, less health
      and welfare service use, and lower risk of mortality 1 year later than members of
      the three problem health classes. Those with comorbid health problems were
      predicted to have particularly poor outcomes. CONCLUSIONS: A latent class
      approach to modelling self-reported health problems and symptoms has allowed for
      both quantitative and qualitative dimensions of health status to be captured.
      This may motivate better informed models of health by users of general population
      surveys.

PMID- 14575197
TI  - Workload implications of identifying patients with ischaemic heart disease in
      primary care: population-based study.
AB  - BACKGROUND: The aims of this study were to develop ischaemic heart disease (IHD)
      registers in three primary care groups (PCGs) in SW London; to determine what
      proportion of patients with IHD were already identified; and to estimate the
      workload in producing an IHD disease register. METHODS: A population-based cross
      sectional study was carried out in 46 out of 49 general practices in three PCGs
      in SW London, using computerized and paper medical records. Outcome measures were
      proportion of patients with IHD on existing disease registers, and workload and
      cost of producing complete registers. RESULTS: Of 3803 patients with a pre
      existing IHD Read code, 570 (15 per cent) were found to have no evidence of IHD,
      leaving 3233 patients with confirmed or probable IHD. A search of 7726 patients
      prescribed one of five cardiovascular drugs but not already coded as having IHD
      identified a further 1447 confirmed or probable cases. On average, coders spent
      4.9 hours per 1000 list size verifying IHD cases or finding uncoded cases. Each
      additional IHD case required about 0.68 hours (41 minutes) of coder's time to
      identify and one case of IHD was identified or confirmed for about every five
      sets of notes examined. The cost of each additional case identified was about
      pounds sterling 10.20. At practice level, there was a wide variation in the
      proportion of IHD patients already on the register or wrongly coded as having
      IHD. CONCLUSIONS: A centralized search programme can identify patients with IHD
      efficiently and at relatively low cost. As the identification of cases is an
      essential first step in implementing effective secondary prevention, other
      primary care trusts may also find this method useful in improving the management
      of patients with IHD.

PMID- 14575198
TI  - Social deprivation and breast cancer.
AB  - BACKGROUND: This cross-sectional study was carried out in a population-based
      setting in Worcestershire to investigate the relationship between social
      deprivation and other potential prognostic factors. METHODS: A total of 762
      female patients diagnosed with primary breast cancer between 1 January 1998 and
      31 December 1999 were selected. Breast cancer included all new cases of primary
      invasive breast cancer and ductal carcinoma in situ. A total of 753 patients were
      matched by their postcode of residence to enumeration district Townsend score and
      then divided into three groups based on Townsend quintiles (affluent n = 478;
      middle n = 157; deprived n = 118). Main outcome measures were relationships
      between social deprivation and tumour type, stage at presentation, oestrogen
      receptor status, tumour grade and treatment type. RESULTS: Compared with the most
      deprived women, affluent women were less likely to present with invasive ductal
      tumours (70.8 per cent versus 85.9 per cent, chi2 linear trend = 6.757, p =
      0.009), tumours of higher grade (36.0 per cent versus 44.7 per cent, chi2 linear
      trend = 4.201, p = 0.040), and oestrogen receptor negative tumours (22.4 per cent
      versus 33.3 per cent, chi2 linear trend = 3.501, p = 0.061). There was no
      significant difference in stage or tumour size at presentation between
      deprivation groups. More deprived women with invasive tumours of less than 20 mm
      maximum diameter were significantly more likely to have mastectomies than
      affluent women (47.8 per cent versus 32.1 per cent, chi2 linear trend = 4.091, p
      = 0.043). CONCLUSIONS: This study suggests that level of social deprivation is
      associated with tumour type, grade and oestrogen receptor status. There was also
      a suggestion that increased level of deprivation was associated with increased
      risk of potentially unnecessary mastectomies.

PMID- 14575199
TI  - Integrated Pollution Prevention and Control: a review of health authorities'
      experience.
AB  - In August 2000, health authorities in England and Wales became statutory
      consultees for permits issued to industry by the Environment Agency as part of
      the implementation of EU directives. This responsibility has since been delegated
      to Primary Care Trusts. To assess health authority responses to applications made
      under the Integrated Pollution Prevention and Control (IPPC) regulations, we
      collected data from public registers during the first 12 months of this new
      regulatory regime. There was evidence of 27 applications, of which 59 per cent
      had substantive comments from health authorities. There was wide variation in the
      length and content. Responses were from Consultants in Communicable Disease
      Control (57 per cent) or Directors of Public Health (43 per cent). Only two
      health authorities had a dedicated resource for responding to IPPC applications.
      Capacity and capability are lacking and require resources invested for
      consistent, effective public health input to the process of permitting
      potentially polluting industries.

PMID- 14575200
TI  - Risk of congenital anomalies near the Byker waste combustion plant.
AB  - BACKGROUND: The aim of this study was to determine whether the risk of congenital
      anomalies in a population resident close to a waste combustion plant located at
      Byker in the city of Newcastle upon Tyne, United Kingdom, was higher than in a
      population resident further away. METHODS: A geographical study was carried out
      on the prevalence of congenital anomalies in residents living within 3 km (inner
      zone) of the Byker combustion plant compared with those living 3-7 km (outer
      zone) from the plant. There were 81255 live births (1985-1999) and 1508 cases
      with chromosomal and non-chromosomal congenital anomalies. The cases were
      identified from the Northern Region Congenital Abnormality Survey. RESULTS: After
      the site commenced operation the estimated rate ratio (inner versus outer zone)
      was 1.11 (95 per cent confidence interval (CI) 0.96-1.28) adjusted for socio
      economic deprivation. There was significant heterogeneity across years and an
      increasing trend, of marginal significance (p = 0.07), in the rate ratio. The
      inner zone rate approached or became significantly higher than that in the outer
      zone in some of the later years. CONCLUSIONS: No significant overall association
      between the number of congenital anomalies and proximity of residence to the
      Byker waste combustion plant has been found in this study. Significantly
      increased rates near the site during the later years may suggest a possible risk
      but are difficult to interpret. More comprehensive, multi-site investigations
      around other waste combustion plants are indicated.

PMID- 14575201
TI  - Health impact assessment and the consideration of health inequalities.
AB  - Equity and the consideration of the differential impacts of public policy within
      populations are core values of health impact assessment. A recent paper setting
      out the results of the government's consultation exercise on tackling health
      inequalities argues for health impact assessment to be used as a mechanism to
      bring about reductions in health inequalities. However, we would contend that
      most, if not all, published health impact assessments have not considered the
      effects of public policies on health inequalities in a robust or reliable manner.
      In this paper we set out and explore some of the issues that require
      consideration if health impact assessment is fulfil the government's
      expectations.

PMID- 14575202
TI  - A preliminary study on the relation between thunderstorms and mortality of in
      patients.
AB  - BACKGROUND: The aim of this study was to investigate the association between
      thunderstorms and mortality of in-patients. METHODS: Data for in-patients and
      deaths in internal medicine departments from four hospitals in Shanghai were
      collected and grouped according to meteorological conditions. RESULTS: Weekly
      mortality of in-patients was significantly higher on days with thunderstorms than
      on fine days. This effect was significant for patients in respiratory,
      cardiovascular and neurology wards but not in the wards of other specialties.

PMID- 14575203
TI  - Trends in mortality rates comparing underlying-cause and multiple-cause coding in
      an English population 1979-1998.
AB  - Until recently, national coding and analysis of routine mortality statistics in
      most countries included only underlying cause of death. There were changes in the
      rules for selection and coding of underlying cause in England in 1984 and 1993.
      We report on trends in mortality rates in an English region from 1979 to 1998,
      comparing multiple-cause and underlying-cause coded rates, for individual
      diseases that were affected by coding changes. Among many others, these include
      pneumonia, venous thromboembolism, heart failure, respiratory distress syndrome,
      tuberculosis, diabetes, dementia, alcohol and drug abuse, epilepsy, multiple
      sclerosis, stroke, asthma, peptic ulcer, appendicitis, and cancers of the breast,
      colon and prostate. Comparisons over time of mortality rates based on underlying
      cause alone will be misleading when the time-period crosses years in which rules
      changed for selecting underlying cause.

PMID- 14575204
TI  - Prevalence estimates for chronic diseases in Italy: exploring the differences
      between self-report and primary care databases.
AB  - BACKGROUND: The aim of this study was to describe population and primary care
      morbidity and to examine how the differences vary across the diseases and are
      influenced by patients' demographic characteristics. METHODS: A comparison of the
      prevalence of four chronic conditions for 432747 patients from the Health Search
      Database (HSD) and 119799 individuals from a Health Interview Survey was carried
      out. A linear regression was performed to study the associations between age and
      difference in morbidity. RESULTS: Similar prevalence was found for diabetes and
      hypertension, whereas for chronic obstructive pulmonary disease (COPD) and
      gastroduodenal ulcer lower HSD prevalence was reported. Among females, age was
      always associated with morbidity difference. Among males, significant
      associations were found only for COPD (R2 = 0.81; p = 0.001) and gastroduodenal
      ulcer (R2 = 0.93; p < 0.001). CONCLUSIONS: The difference between population and
      primary care morbidity is affected by disease under investigation and patients'
      demographic characteristics. Therefore, in choosing the more cost-effective
      approach to collect data such evidence should be taken into account, and results
      should be interpreted with great caution.

PMID- 14575205
TI  - The impact of chronic disease management in primary care on inequality in asthma
      severity.
AB  - Chronic disease management (CDM) is now widely available in primary care, but
      methods of delivery are highly variable. The focus of this study was to examine
      whether CDM provided in asthma clinics was more effective in reducing the
      severity of asthma symptoms, particularly for deprived populations. There was no
      evidence of 'inverse care' in the provision of CDM in clinics and good evidence
      that it was associated with a reduction in the severity of asthma symptoms for
      both deprived and affluent populations.

PMID- 14575206
TI  - Reducing inequalities in non-fatal accidents in England.
AB  - We investigated rates of non-fatal accidents recorded in the Health Survey for
      England. Between 1995/96 and 2001, rates fell in men although not in women. In
      contrast to other trends for health behaviours in the United Kingdom, for example
      smoking, there was no increased gap between male manual and non-manual groups.

PMID- 14575207
TI  - Cluster investigation--the importance of counting everyone.

PMID- 14575208
TI  - Evidence-based public health: improving the relevance of Cochrane Collaboration
      systematic reviews to global public health priorities.

PMID- 14575209
TI  - Communicable disease and health protection quarterly review: January to March
      2003--from the PHLS communicable disease surveillance centre.

PMID- 14575210
TI  - Primary care doctors and population health.

PMID- 14575211
TI  - Shining the light-public health observatories in England.

PMID- 14575212
TI  - Very high cost treatment for a single individual.

PMID- 14575214
TI  - Patterns of physical activity.

PMID- 14575215
TI  - Gravity of human genome project on clinical medicine.

PMID- 14575216
TI  - A study on the serum levels of interleukin-1beta in bronchial asthma.
AB  - Mononuclear phagocytes can be activated through an immunoglobulin E (IgE)-
      specific mechanism to release pro-inflammatory cytokine like interleukin-1beta
      (IL-1beta). The present study was conducted to show the inter-relationship
      between these two parameters in the serum of asthmatic patients. The study
      included 30 patients of asthma and 10 as control. Out of these 30 cases, 20
      patients had stable and 10 had acute asthma. Of the 20 stable patients, 9 were
      allergic and 11 were non-allergic to either of the 12 allergens used for skin
      prick test. Serum IgE and IL-1beta levels were measured by enzyme linked
      immunosorbent assay (ELISA). Total serum IgE levels increased significantly (p <
      0.05) in asthma [200.5 +/- 30.91 IU/ml, mean +/- standard error of mean (SEM)] in
      comparison with the controls (18.15 +/- 4.35 IU/ml). Serum IL-1beta level was
      higher in allergic (1.94 +/- 0.63 pg/ml) than in non-allergic patients (0.64 +/-
      0.21 pg/ml) but it was not statistically significant (p > 0.05). The study
      suggests involvement of IgE and IL-1beta in the pathophysiology of allergic
      asthmatic condition. Further studies are required to delineate the inflammatory
      pathway in asthma and determine stages at which therapeutic interventions can be
      done.

PMID- 14575217
TI  - Cases of human immunodeficiency virus infection and tuberculosis--early
      experiences of different aspects.
AB  - An outpatients department based survey conducted in Calcutta amongst 1349
      established cases of tuberculosis (TB) revealed 0.67% human immunodeficiency
      virus (HIV) infected cases. Those affected by HIV and TB did not show any
      deviation from epidemiological pattern of HIV infection in India. All contracted
      HIV infection by heterosexual route, mostly from Bombay (47.8%) followed by West
      Bengal (30.4%). In follow-up study of a cohort of 36 HIV seropositives over 3
      years, 10(27.7%) developed TB. Of the 23 HIV infected cases with TB, lesions were
      mostly pulmonary (n = 18, 78.3%) followed by pleural effusion (n = 3;13%). Low
      incidence of Mycobacterium avium (intracelluarae) complex and tuberculous
      lymphadenopathy one case each and 52.2% positivity with 14.5 mm mean induration
      diameter in intradermal test with one TU PPD-RT23 are deviations from previous
      reports. Low incidence of cough (43.5%), marked weight loss (100%) and fever
      (100%) were the cardinal clinical features. TB infection on pattern suggestive of
      reactivation of dormant pulmonary lesions lower rate (11%) of treatment failure
      and infection caused by organisms other than Mycobacterium tuberculosis were
      other findings of the study. Importance of serosurveillance to unearth more TB
      cases amongst HIV infected cases for early treatment and isoniazid prophylaxis is
      stressed upon.

PMID- 14575218
TI  - Epidemiological study of neurological disorders in a rural population of Eastern
      India.
AB  - The study was conducted to determine the prevalence of neurological diseases in a
      rural community in Eastern India through a community based survey with the help
      of trained doctors following on WHO protocol (1981) translated in local
      vernacular, among 20842 rural residents (male-11037, female-9805, census India
      1991, the State of West Bengal in Eastern India) over a period of one yearfrom
      May 1992 to April 1993 in two phases. Professionals screened the patients by
      house to house survey in the first phase and later on they were examined in
      details in temporary clinics in second phase. A total of 606 patients were
      identified and classified according to well-defined diagnostic criteria. The
      commonest diseases per 100,000 were headache: 870, vertebral diseases with
      neurological involvement: 540, seizure disorders: 360, vertigo: 230, stroke: 147,
      movement disorders: 140, peripheral neuropathy: 80. The age and sex specific
      prevalence showed increasing frequency of neurological disorders with advancing
      age in both genders excepting slight dip in the fourth and fifth decades among
      females. In the present study prevalence of headache, epilepsy, stroke and
      Parkinson's disease was lower than that of in the Western countries. Different
      inclusion criteria, multiethnicity, different environmental factors, poor medical
      facility and insufficient number of aged population may be responsible for lower
      prevalence of chronic neurological disorders as compared to Western countries.
      Increase in the life expectancy in future will lead to increasing burden of
      chronic neurological diseases in absolute term in Indian society considering the
      one billion population at present.

PMID- 14575219
TI  - Recent trend in the treatment of dysfunctional uterine bleeding.
AB  - Dysfunctional uterine bleeding (DUB) is defined as excessive uterine bleeding
      with no demonstrable organic cause either genital or extra-genital. Management of
      DUB should be individualised. The general measures, conservative approach,
      radical therapy and surgery as treatment modalities, as practised have been
      detailed here.

PMID- 14575220
TI  - Severe acute respiratory syndrome: a preliminary review.
AB  - Severe acute respiratory syndrome (SARS) is a new disease of unknown aetiology
      and probably a new strain of coronavirus is thought to be responsible for the
      disease. After originating from south-east China it has spread to several
      countries across the world. Patients of SARS suffer from fever with cough and
      dyspnoea. The virus spreads by droplet to nearby contacts and has high tendency
      to spread to the healthcare providers. Since the aetiology is not yet clear exact
      treatment is not yet defined and hence prevention is of utmost importance.

PMID- 14575221
TI  - ACE inhibitors and beta blockers in chronic congestive cardiac failure:
      therapeutic basis.
AB  - Congestive cardiac failure (CCF) is a common problem through out the globe and is
      associated with high morbidity and mortality. The rapid progression of the
      disease due to neurohormonal activation can be blunted by use of angiotensin
      converting enzyme inhibitor (ACEI) and beta blockers (BB) with a major impact on
      morbidity and mortality. Besides CCF, they are also useful in asymptomatic left
      ventricular dysfunction (LVD) and in prevention of heart failure in high risk
      patients without LVD. Both ACEI and BB are highly underutilised therapy in CCF
      and there is an urgent necessity to spread message among the medical fraternity
      for their enhanced use.

PMID- 14575222
TI  - Insulinoma-a case report.
AB  - BNM, a 40 years Hindu male presented with history of intermittent fainting
      attacks and had increase in body weight for last 2 years. He used to take a lot
      of sweets to recover from the attact. His body wht was 100 kg. His fasting blood
      sugar was 50 mg/dl and insulin glucose (I/G) ratio was 0.6. CT scan of abdomen
      showed one solitary tumour in the body of pancreas near its tail. Laparotomy was
      done. The tumour was found to be a benign insulinoma on microscopic examination.
      Though the postoperative period was uneventful but he succumbed probably due to
      pulmonary embolism.

PMID- 14575223
TI  - Follicular carcinoma of thyroid with synchronous bony and soft tissue metastases.
AB  - A 65 years old lady presented with a large thyroid swelling along with a soft,
      non-tender mass over the left parietal region and a small, hard, non-tender
      swelling over the volar aspect of right forearm. FNAC reports from the thyroid
      gland and the swellings over head and forearm all revealed features of follicular
      neoplasm. Excision biopsy of the forearm swelling showed histology of metastatic
      poorly differentiated follicular adenocarcinoma of thyroid. The patient underwent
      total thyroidectomy followed by excision of the mass over the head, a week later.
      She was discharged in favourable condition with advice to attend oncology
      department for subsequent management. She is yet to attend surgical outdoor for
      follow-up.

PMID- 14575224
TI  - Neonatal hypernatraemic dehydration and malnutrition associated with inadequate
      breastfeeding and elevated breast milk sodium.
AB  - The advantages of breastfeedng to both the mother and infant are well recognised.
      In rare instances if breasteding is inadequate or if the sodium content bast milk
      is high, malnutrition and hypernatraemia can result. A 15 days old exclusively
      breastfed baby presented with inadequate weight gain. On evaluation, he was found
      to have hypernatraemia and mother's breast milk showed high sodium
      concentrations. The infant needed parenteral fluid for correction of dehydration
      and hypernatraemia. His serum sodium and breast milk sodium of the other of the
      mother returned to normal gradually. He started gaining weight on exclusive
      breastfeeds. The present paper describes the case report and brief review of the
      literature.

PMID- 14575225
TI  - An unusual abdominal lumpa--a case report.
AB  - A 58 years old male presented with a self detected upper abdominal mass of 6
      months duration along with recent history of weight loss and malaise.
      Ultrasonography (USG) of abdomen showed a hypoechoic mass with cystic areas,
      approximately 10 cm x 7 cm in measurement, occupying the upper abdomen and lying
      in front of the stomach. Endoscopy revealed extrinsic compression of the anterior
      wall of the stomach without any detectable abnormality of the gastric and
      duodenal mucosa. CT scan of the abdomen showed a well defined heterogeneous mass
      with cystic areas, attached to the anterior stomach wall by a narrow stalk.
      Surgical resection of the mass along with a strip of stomach wall adjoining the
      stalk and the adherent omentum was performed. Few lymph nodes were sampled.
      Biopsy report suggested gastric leiomyoma and the lymph nodes did not reveal any
      tumour deposit. Patient is doing well more than a year after surgery.

PMID- 14575226
TI  - Mason diabetes--report of a family.
AB  - A 48-year-old Hindu housewife was presented with increased appetite, thirst,
      frequency of micturition, weakness, cramps in the legs, tingling in the fingers,
      decline in bladder-bowel control and dimness of vision. She was a patient of
      diabetes. On investigations and history, she was diagnosed as a case of type 2
      diabetes transmitted in three generations as an autosomal dominant trait.

PMID- 14575227
TI  - JIMA for family physicians.

PMID- 14575229
TI  - Burn--the hypothesis.

PMID- 14575228
TI  - Principles of palliative care.

PMID- 14575230
TI  - Diabetic foot ulcers.

PMID- 14575231
TI  - Doctor's dilemma.

PMID- 14575232
TI  - Comparison of the efficacy, safety and tolerability of telmisartan with losartan
      in Indian patients with mild to moderate hypertension: a pilot study.
AB  - A prospective, randomised, double-blind, parallel group study was carried out to
      compare the efficacy, safety and tolerability of telmisartan 40 mg once daily
      with losartan 50 mg once daily in Indian patients with mild to moderate
      hypertension. It had a placebo run-in period of 2 weeks followed by drug
      treatment (telmisartan 40 mg, once daily or losartan 50 mg once daily) for 8
      weeks. Supine BP was assessed at the end of every 2 weeks. Tolerability and
      safety was assessed by physical examination, laboratory parameters and evaluation
      of adverse events. Treatment with telmisartan resulted in a significant reduction
      of SBP of 10.3% and 13.7% as compared to 6.6% and 10.6% in losartan group at the
      end of 6th and 8th weeks respectively. At the end of 6th and 8th weeks, the
      reduction was 14.3% and 18.1% among telmisartan which was significantly more as
      compared to 8.8% and 14.3% in losartan group respectively. The laboratory values
      were within normal limits. Both drugs were well tolerated. Telmisartan
      monotherapy in a dose of 40 mg once daily has a clinically better therapeutic
      effect as compared to losartan 50 mg and a good tolerability profile in patients
      with mild to moderate hypertension.

PMID- 14575233
TI  - Efficacy and tolerability of a combination of ofloxacin and tinidazole in the
      management of infectious diabetic foot ulcer.
AB  - The management of infectious diabetic foot ulcers is a major concern. Various
      treatment modalities are used. The efficacy and tolerability of a combination of
      ofloxacin and tinidazole in diabetic foot ulcer has been assessed in 60 patients
      in the present trial. The results are promising.

PMID- 14575234
TI  - Congenital fiber type disproportion--30 years on.
AB  - Thirty years ago, M. H. Brooke coined the term "congenital fiber type
      disproportion" (CFTD) to describe 12 children who had clinical features of a
      congenital myopathy and relative type 1 fiber hypotrophy on muscle biopsy. It is
      now clear that this histological pattern can accompany a wide range of
      neurological disorders, leading to disillusionment with CFTD as a distinct
      nosological entity. To determine whether the CFTD has clinical utility as a
      diagnostic entity, we have reviewed the literature for cases of type 1 fiber
      hypotrophy and have used strict exclusion criteria to identify 67 cases of CFTD.
      Most patients presented at birth with weakness and hypotonia, had normal
      intelligence, and followed a static or improving clinical course. In 43% of
      families, more than 1 individual was affected. Failure to thrive was common and
      25% of patients had contractures or spinal deformities. Bulbar weakness and
      ophthalmoplegia were less common and cardiac involvement was rare. Twenty-five
      percent followed a severe course and 10% had died at the time of reporting, all
      from respiratory failure. Ophthalmoplegia and facial and bulbar weakness were
      significantly associated with a poorer prognosis. The relatively homogeneous
      phenotype supports the retention of CFTD as a distinct diagnostic entity and
      familial occurrence suggests a genetic basis. Regarding the diagnosis of CFTD, we
      found no strong evidence that the minimum difference between type 1 and type 2
      fiber sizes should be increased from 12% to 25%. We also list the other reported
      causes of relative type 1 fiber hypotrophy to aid their exclusion from CFTD.

PMID- 14575235
TI  - Neuropathological and ultrastructural features of amebic encephalitis caused by
      Sappinia diploidea.
AB  - Here we present the neuropathological, ultrastructural, and radiological features
      of Sappinia diploidea, a newly recognized human pathogen. The patient was a 38
      year-old man with visual disturbances, headache, and a seizure. Brain images
      showed a solitary mass in the posterior left temporal lobe. The mass was composed
      of necrotizing hemorrhagic inflammation that contained free-living amebae.
      Immunofluorescence microscopy showed that the organism was not a species of ameba
      previously known to cause encephalitis. Trophozoites had a highly distinctive
      double nucleus, and transmission electron microscopy confirmed that they
      contained 2 nuclei closely apposed along a flattened surface. The 2 nuclei were
      attached to each other by distinctive connecting perpendicular filaments. This
      and several other unique structural features led to the diagnosis of S. diploidea
      encephalitis. The patient was treated postoperatively with a sequential regimen
      of anti-amebic drugs (azithromycin, pentamidine, itraconazole, and flucytosine)
      and is alive after 5 years. Guidelines to recognize future cases of S. diploidea
      encephalitis are as follows. 1) It presented as a tumor-like cerebral mass
      without an abscess wall. 2) It had central necrotic and hemorrhagic inflammation
      that contained acute and chronic inflammatory cells without granulomas or
      eosinophils. 3) It contained trophozoites (40-70 microm diameter) that contained
      a distinctive double nucleus. 4) Cyst forms in the host were not excluded or
      definitely evident. 5) Trophozoites engulfed host blood cells and were stained
      brightly with Giemsa and periodic acid-Schiff. 6) Trophozoites often were present
      in viable brain parenchyma on the periphery of the mass without inflammatory
      response. 7) The prognosis after surgical excision and medical treatment was
      favorable in this instance.

PMID- 14575236
TI  - Lack of association between the levels of the low-density lipoprotein receptor
      related protein (LRP) and either Alzheimer dementia or LRP exon 3 genotype.
AB  - The low-density lipoprotein receptor-related protein (LRP), which interacts with
      the Alzheimer disease (AD) beta-amyloid precursor protein (APP), represents an
      important pathway in AD pathology. LRP-mediated receptor pathways appear to
      regulate both the production and the clearance of amyloid beta-protein (Abeta), a
      principal neuropathological product in AD. Several conflicting studies have
      examined levels of LRP in AD brains, as well as the relationship between the LRP
      exon 3 (C766T) polymorphism and LRP levels and/or disease susceptibility. In
      order to further investigate the role of LRP in AD, we examined well
      characterized brain samples collected from subjects with varying degrees of
      cognitive impairment for LRP protein expression levels as well as for the
      presence of the LRP exon 3 polymorphism. We found no correlation between LRP
      levels and either presence of the disease or cognitive decline. In addition, we
      found no correlation between the LRP exon 3 polymorphism and either AD or LRP
      levels.

PMID- 14575239
TI  - Distribution of GABAA receptor mRNA in the motor cortex of ALS patients.
AB  - The pathomechanism of amyotrophic lateral sclerosis (ALS) remains unclear. There
      is some evidence that excitotoxic cell death is involved in the degeneration of
      the motor nervous system, and that ligand-gated receptor channels play a role in
      the pathogenesis of the disease. Several electrophysiological and anatomical
      studies support the pathophysiological concept of an impaired inhibitory, namely
      GABAergic, control of the motoneurons in the cerebral cortex of ALS patients. The
      aim of our study was to investigate the expression of GABAA-receptor subunit
      mRNAs and the GABA synthesizing enzyme glutamic acid decarboxylase (GAD) in the
      motor cortex of ALS patients compared to tissue of control persons. We performed
      in situ hybridization histochemistry (ISH) on human postmortem motor cortex
      sections of ALS patients (n = 5) and age matched controls with no history of
      neurological disease (n = 5). The most intriguing finding was a significantly
      reduced mRNA expression of the alpha1-subunit in ALS patients while the level of
      beta1-subunit mRNA was elevated in the patients group. This may indicate specific
      alterations of the GABAA receptor subunit composition and result in distinct
      physiological and pharmacological properties of these receptors in ALS patients.

PMID- 14575237
TI  - Gene expression profiling in ataxin-3 expressing cell lines reveals distinct
      effects of normal and mutant ataxin-3.
AB  - Spinocerebellar ataxia type 3 (SCA3) is a late-onset neurodegenerative disorder
      caused by the expansion of a polyglutamine tract within the gene product, ataxin
      3. We have previously shown that mutant ataxin-3 causes upregulation of
      inflammatory genes in transgenic SCA3 cell lines and human SCA3 pontine neurons.
      We report here a complex pattern of transcriptional changes by microarray gene
      expression profiling and Northern blot analysis in a SCA3 cell model. Twenty
      three differentially expressed genes involved in inflammatory reactions, nuclear
      transcription, and cell surface-associated processes were identified. The
      identified corresponding proteins were analyzed by immunohistochemistry in human
      disease and control brain tissue to evaluate their implication in SCA3
      pathogenesis. In addition to several inflammatory mediators upregulated in mutant
      ataxin-3 expressing cell lines and pontine neurons of SCA3 patients, we
      identified a profound repression of genes encoding cell surface-associated
      proteins in cells overexpressing normal ataxin-3. Correspondingly, these genes
      were upregulated in mutant ataxin-3 expressing cell lines and in pontine neurons
      of SCA3 patients. These findings identify for the first time target genes
      transcriptionally regulated by normal ataxin-3 and support the hypothesis that
      both loss of normal ataxin-3 and gain of function through protein-protein
      interacting properties of mutant ataxin-3 contribute to SCA3 pathogenesis.

PMID- 14575238
TI  - Cellular mechanisms involved in the stenosis and obliteration of the cerebral
      aqueduct of hyh mutant mice developing congenital hydrocephalus.
AB  - Two phases may be recognized in the development of congenital hydrocephalus in
      the hyh mutant mouse. During embryonic life the detachment of the ventral
      ependyma is followed by a moderate hydrocephalus. During the first postnatal week
      the cerebral aqueduct becomes obliterated and a severe hydrocephalus develops.
      The aim of the present investigation was to elucidate the cellular phenomena
      occurring at the site of aqueduct obliteration and the probable participation of
      the subcommissural organ in this process. Electron microscopy,
      immunocytochemistry, and lectin histochemistry were used to investigate the
      aqueduct of normal and hydrocephalic hyh mice from embryonic day 14 (E-14) to
      postnatal day 7 (PN-7). In the normal hyh mouse, the aqueduct is an irregularly
      shaped cavity with 3 distinct regions (rostral, middle, and caudal) lined by
      various types of ependyma. In the hydrocephalic mouse, these 3 regions behave
      differently; the rostral end becomes stenosed, the middle third dilates, and the
      caudal end obliterates. The findings indicate that the following sequence of
      events lead to hydrocephalus: 1) denudation of the ventral ependyma (embryonic
      life); 2) denudation of dorsal ependyma and failure of the subcommissural organ
      to form Reissner fiber (first postnatal week); 3) obliteration of distal end of
      aqueduct; and 4) severe hydrocephalus. No evidence was obtained that NCAM is
      involved in the detachment of ependymal cells. The process of ependymal
      denudation would involve alterations of the surface sialoglycoproteins of the
      ependymal cells and the interaction of the latter with macrophages.

PMID- 14575240
TI  - Expression of the oligodendroglial lineage-associated markers Olig1 and Olig2 in
      different types of human gliomas.
AB  - Because a specific group of oligodendrogliomas is susceptible to adjuvant
      therapy, it is important to elucidate the biological characteristics of these
      tumors. In situ hybridization analyses have revealed that Olig genes are
      expressed in oligodendroglial lineage cells and are highly expressed in
      oligodendrogliomas. To clarify whether OLIG is a tumor-specific marker for
      oligodendrogliomas, we have investigated the expression of Olig transcripts by
      semiquantitative RT-PCR assay and OLIG2 protein with a new antibody in a variety
      of glial tumors. The semiquantitative RT-PCR revealed that high levels of
      expression of Olig1 and Olig2 mRNAs were present in anaplastic oligodendrogliomas
      and anaplastic astrocytomas, while expression of these mRNAs in grade IV
      glioblastomas was lower than in grade II and grade III gliomas (p < 0.01).
      Immunohistochemical analyses demonstrated that the mean immunopositive proportion
      of OLIG2 was 82% in anaplastic oligodendrogliomas but only 34% in anaplastic
      astrocytomas. Therefore, although OLIG2 expression was detected in a range of
      gliomas not specific for oligodendrogliomas, the expression level in anaplastic
      oligodendrogliomas was more uniform and intense than that in other glial tumors.
      In conclusion, combining Olig mRNA expression and immunohistochemistry of OLIG2
      enables oligodendrogliomas to be distinguished from glioblastomas and other
      astrocytic glial tumors.

PMID- 14575241
TI  - Mapping of rat brain using the Synuclein-1 monoclonal antibody reveals
      somatodendritic expression of alpha-synuclein in populations of neurons
      homologous to those vulnerable to Lewy body formation in human synucleopathies.
AB  - The neuronal protein alpha-synuclein has been implicated in the pathogenesis of
      Parkinson disease and other neurodegenerative diseases. Although many studies
      report that alpha-synuclein expression is restricted to neuronal presynaptic
      terminals, this protein aggregates in Lewy bodies in somata that are typically
      distant from their axon terminals. Few studies have addressed this paradox and
      there has been no compelling explanation proposed for the apparent discrepancy
      between the locus of neuronal alpha-synuclein expression and the loci of Lewy
      bodies in the majority of Parkinson disease cases. We explored this issue by
      extensively characterizing the monoclonal antibody Synuclein-1 (Syn-1) and using
      this highly selective antibody to map the distribution of alpha-synuclein
      throughout rat brain and in human substantia nigra (SN). Additionally, alpha
      synuclein expression in rat SN detected by 2 polyclonal antibodies against alpha
      synuclein was compared with that detected by the Syn-1 antibody. In contrast with
      many previous reports, alpha-synuclein was detected by Syn-1 in neuronal somata
      and dendrites in restricted brain regions, as well as more ubiquitously in axons
      and terminals. The strongest alpha-synuclein neuronal expression in rat was found
      in brainstem and cortical regions that are homologous to regions prone to Lewy
      body formation in humans. The Syn-1 antibody labeled abundant somatodendritic
      alpha-synuclein in both rat and human SN, a major locus of Lewy body formation
      and neurodegeneration in Parkinson disease. By contrast, very few immunoreactive
      somata in the rat SN were labeled by the 2 polyclonal antibodies. We explore
      possible explanations for the differences in conflicting reports of patterns of
      alpha-synuclein expression in brain, including differences among antibodies.

PMID- 14575242
TI  - NMDA receptor 1 expression in the brainstem of human infants and its relevance to
      the sudden infant death syndrome (SIDS).
AB  - The N-methyl-D-aspartate (NMDA) glutamatergic receptor is widely expressed in the
      brain during the early postnatal period and, among other functions is involved in
      cardiorespiratory control and in cell death by excitotoxic mechanisms. This study
      examined NMDA receptor-1 (NR1) expression in the human infant brainstem and
      assessed whether expression differed between non-SIDS and SIDS infants. NRI mRNA
      was identified using non-radioactive in situ hybridization and quantified by
      optical density. NRI protein was identified by immunohistochemistry and
      quantified by cellular counting. Eight nuclei of the mid-medulla and 2 nuclei of
      the rostral pons were studied. NRI mRNA and protein were expressed in all nuclei
      studied, confirming that the NMDA receptor is widely distributed in the human
      infant brainstem. Compared to non-SIDS infants (n = 10). SIDS infants (n = 15)
      had increased mRNA in 6 nuclei of the mid-medulla (p < 0.05 for all) while
      protein was increased in the dorsal motor nucleus of the vagus (p = 0.04) and
      decreased in the nucleus of the spinal trigeminal tract (p = 0.03). No
      differences were observed in the rostral pons. This preliminary study suggests
      that abnormalities of the glutamatergic system are present in SIDS victims.
      Further studies will be required to delineate these abnormalities and to
      investigate potential underlying mechanisms and sequelae.

PMID- 14575243
TI  - Clinical biomechanics of wear in total hip arthroplasty.
AB  - Complementary clinical and laboratory studies were performed to identify
      variables associated with polyethylene wear following total hip replacement, and
      to elucidate the mechanisms responsible for accelerated wear in the total hip
      arthroplasty construct. Observational cohort studies were performed using a
      prospective clinical database of more than 4000 consecutive primary total hip
      arthroplasties performed by a single surgeon, to identify wear-related variables.
      These variables included head size, acetabular/femoral component impingement, and
      third body debris. Novel digital edge detection techniques were developed and
      employed to accurately measure wear, and to determine the relationships of head
      size and third body debris to acceleration of wear. A novel sliding-distance
      coupled finite element model was formulated and employed to examine the
      mechanisms responsible for wear. The long-term cohort studies demonstrated
      smaller head sizes to be associated with less wear. Third body debris generated
      from cable fretting was associated with an increase in wear, osteolysis, and
      acetabular loosening, especially with larger head sizes. The sliding-distance
      coupled finite element model replicated the wear rates occurring in vitro and in
      vivo, demonstrating the importance of sliding distance on polyethylene wear
      following total hip arthroplasty. It also demonstrated substantial increases in
      wear associated with femoral head scratching from third body debris. Further
      extension of the finite element formulation demonstrated the potential for
      acetabular component rim damage from impingement wear, and the enhanced potential
      for third body ingress to the bearing surface with larger head sizes. Edge
      detection wear measurement techniques demonstrated that early wear rates were
      predictive of long-term wear rates. These complementary clinical and laboratory
      investigations have provided insight into 1) the significance of sliding distance
      and physiologic loci of motion as contributing factors in minimizing wear, 2) the
      deleterious effects of third body particulates in accelerating wear, 3) the
      potential for, and factors related to, impingement wear, and 4) the potential
      advantages and compromises related to the use of larger head sizes in the bearing
      surface construct.

PMID- 14575245
TI  - The Bernese Periacetabular Osteotomy: review of reported outcomes and the early
      experience at the University of Iowa.
AB  - The Bernese Periacetabular Osteotomy (PAO) is an operation designed to relieve
      hip pain and improve function in patients with symptomatic dysplastic hips. The
      short-term results of the Bernese PAO indicate that there is a learning curve but
      most patients with dysplasia and mild arthritis have excellent pain relief.
      Outcomes and complications are the primary focus of discussion. Operative data
      and complications from the first 36 patients undergoing the Bernese PAO at the
      University of Iowa have been comparable to those reported in the literature.

PMID- 14575244
TI  - How do tissues respond and adapt to stresses around a prosthesis? A primer on
      finite element stress analysis for orthopaedic surgeons.
AB  - Joint implant design clearly affects long-term outcome. While many implant
      designs have been empirically-based, finite element analysis has the potential to
      identify beneficial and deleterious features prior to clinical trials. Finite
      element analysis is a powerful analytic tool allowing computation of the stress
      and strain distribution throughout an implant construct. Whether it is useful
      depends upon many assumptions and details of the model. Since ultimate failure is
      related to biological factors in addition to mechanical, and since the mechanical
      causes of failure are related to load history, rather than a few loading
      conditions, chief among them is whether the stresses or strains under limited
      loading conditions relate to outcome. Newer approaches can minimize this and the
      many other model limitations. If the surgeon is to critically and properly
      interpret the results in scientific articles and sales literature, he or she must
      have a fundamental understanding of finite element analysis. We outline here the
      major capabilities of finite element analysis, as well as the assumptions and
      limitations.

PMID- 14575246
TI  - The effect of fixation technique on graft position in anterior cruciate ligament
      reconstruction.
AB  - The purpose of this paper was to determine the extent to which the technique used
      in ACL reconstruction and fixation influences graft placement. This is a
      Comparative Radiographic cohort study. Precise graft placement is one of the most
      crucial components of a successful anterior cruciate ligament (ACL)
      reconstruction. Two commonly used techniques of ACL reconstruction are
      arthroscopic bone-patellar tendon-bone (B-PT-B) autograft with interference screw
      fixation and semi-tendinosus and gracilis (ST + G) tendon autograft with
      endobutton femoral and multiple staple belt buckle tibial fixation. Using
      radiographic measurements of bone tunnel position following ACL reconstruction
      this study quantified the extent to which these techniques influenced graft
      placement. Femoral and tibial tunnel position in ACL reconstruction was
      determined using the post-operative radiographs of 40 male patients who had
      undergone ACL reconstruction (20 B-PT-B and 20 ST + G). The primary outcome
      measure was location of bone tunnel position following ACL reconstruction.
      Measurements were based on the guidelines of Amis et al. Femoral tunnel position
      of B-PT-B grafts was an average of 9.36% more anterior in the sagittal plane than
      with ST + G grafts. The mean position of B-PT-B grafts was at 31.11% (SD =
      5.45%). The mean position of the ST + G grafts was 21.76% (SD = 6.62%). This
      difference between the two was found to be significant (p < .001). As
      demonstrated by this study, placement and orientation may vary to accommodate
      technique and fixation. Clinical outcomes measured were similar in both groups.

PMID- 14575247
TI  - Early postoperative mortality following total hip arthroplasty in a community
      setting: a single surgeon experience.
AB  - The senior author performed 4967 total hip arthroplasties, 4164 primary and 803
      revision, between 1970 and 1996 in a community setting. All charts were evaluated
      for postoperative death including in-house, 30, 60, and 90 days following the
      procedure. 1.0 per cent of patients (42) died following a primary procedure and
      0.87 per cent (7) died following a revision procedure within 3 months of surgery.
      The number of in-house deaths were 26 (0.52 per cent), including 21 in the
      primary group (0.5 per cent) and 5 in the revision group (0.62 per cent). In both
      the primary and revision situation and independent of co-morbidities, age greater
      than 70 years was significantly associated with increased risk for post-operative
      mortality (p<0.0001), with 0.44% mortality in patients aged 70 years or younger
      (0.51 per cent primary and 0.00 per cent revision), and 1.45 per cent mortality
      in patients greater than 70 years of age (1.38 per cent primary and 1.86 per cent
      revision). This experience of a single surgeon with a high volume community
      practice performing both primary and revision total hip arthroplasty, documents a
      low but significant incidence of postoperative death in the first 3 months
      following total hip arthroplasty (0.98 per cent).

PMID- 14575248
TI  - Closed locked intramedullary nailing of femoral shaft fractures in the elderly.
AB  - A review was performed of all patients over the age of 60 years who were treated
      with a locked intramedullary nail for a femoral shaft fracture. There were 15
      patients with 16 femoral shaft fractures. Four patients died perioperatively. Of
      the surviving 11 patients with 12 fractures, union occurred in 100 percent. Knee
      range of motion was greater than 100 degrees in 11 of the 12 knees. Nine of the
      11 patients returned to their preoperative level of ambulation. Intramedullary
      nailing of femoral shaft fractures in patients over the age of 60 years is an
      effective method of treatment. The mortality rate in elderly patients who sustain
      this injury is comparable to that seen after a femoral neck fracture in this age.

PMID- 14575249
TI  - Heat generation during ulnar osteotomy with microsagittal saw blades.
AB  - Ulnar shortening osteotomy is a surgical treatment option for patients with
      symptomatic ulnar positive variance for a variety of reasons. Delayed healing and
      nonunion of the osteotomized sites have been reported and present problematic
      complications of this procedure. Studies have shown nonunion rate with transverse
      cuts ranging from 8-15%. The goal is to achieve parallel cuts, thus maximizing
      the contacting bony surface area for a better union rate. The senior surgeon
      attempted using a custom thick blade to insure parallel cuts. The concern is
      whether the heat generated during such a cut would contribute to non-union. It is
      our hypothesis that complications with ulnar shortening osteotomy using a thick
      blade are secondary to excess heat generation. When generated heat surpasses the
      threshold temperature of bone tissue, the organic matrix is irreversibly damaged
      and necrosis of the bony ends may occur. The present study measured the heat
      generation during ulnar osteotomy using different blade thicknesses. Thirty-five
      fresh turkey femurs, having similar size and cortical thickness of the human
      ulna, were used. Loading was done at three different speeds of 0.66, 1.0, and 1.5
      mm/second corresponding respectively to 30, 20, and 10 seconds for the complete
      cut. A general linear statistical model was fitted relating temperature rise to
      three predictive factors: blade thickness, sensor distance, and initial bone
      temperature. There was a statistically significant relationship between
      temperature rise and all three predictor variables at the 99% confidence level.
      There was no statistically significant relationship between temperature rise and
      the number of cuts with the same blade up to 10 times. Compared with the single
      microsagital saw blade, the temperature rise for the double thickness blade was
      14% higher and for the triple thickness blade was 23% higher. The temperature
      rise was inversely related to the speed of the cut. The temperature rise for the
      bone cut in 30 seconds was 1.5 times higher than the temperature rise when the
      bone was cut in 10 seconds. Complications with ulnar shortening osteotomy may be
      secondary to excess heat generation. A new thick saw blade design and the use of
      proper internal/external irrigation may overcome the problem.

PMID- 14575250
TI  - Interobserver error in interpretation of the radiographs for degeneration of the
      lumbar spine.
AB  - We examined 114 segments in 23 patients' lumbar spine plain radiographs affected
      by disc degeneration. Two consultant orthopaedic surgeons, two consultant
      radiologists, and one spine nurse practitioner made independent observations on
      the radiographs. MRI scan films of the corresponding 114 segments were used as a
      gold standard. Kappa coefficients were used to evaluate the interobserver error,
      and the error between the independent observers and the MRI scanning reports. The
      systematic differences between the observers for the diagnosis of the disc
      degeneration at each segment level was recorded. There was significant
      interobserver error between the independent observers. The pairwise interobserver
      agreement ranged from fair to substantial on the plain radiograph observations
      [Weighted kappa coefficient, mean: 0.517 (CI=0.388-0.646)]. The pairwise
      interobserver agreement between the independent observers and the MRI scan ranged
      from fair to moderate [Weighted kappa coefficient, mean: 0.388 (CI=0.259-0.518)].
      There is significant error in interpretation of the plain radiographs for the
      diagnosis of lumbar disc degeneration. MRI may be more accurate in the diagnosis
      of lumbar disc degeneration.

PMID- 14575251
TI  - Rationale for treatment of hip abductor pain syndrome.
AB  - Patients with lower back or buttock pain that radiates into the posterior or
      lateral leg are often referred to physical therapy with a diagnosis of sciatica.
      Often the physical exam does not reveal neurologic findings indicative of
      radiculopathy. Instead, there is hip abductor muscle pain and weakness. This
      syndrome involves muscle imbalances that result in overuse strain of the gluteus
      medius and gluteus minimus muscles, myofascial trigger points, and trochanteric
      bursitis. This paper describes hip abductor pain syndrome and provides a
      rationale for the diagnosis and treatment.

PMID- 14575252
TI  - Evidence-based medicine in orthopaedic surgery--a way to the future.

PMID- 14575253
TI  - Osteochondral repair of primate knee femoral and patellar articular surfaces:
      implications for preventing post-traumatic osteoarthritis.
AB  - The risk of post-traumatic osteoarthritis following an intra-articular fracture
      is determined to large extent by the success or failure of osteochondral repair.
      To measure the efficacy of osteochondral repair in a primate and determine if
      osteochondral repair differs in the patella (PA) and the medial femoral condyle
      (FC) and if passive motion treatment affects osteochondral repair, we created 3.2
      mm diameter 4.0 mm deep osteochondral defects of the articular surfaces of the PA
      and FC in both knees of twelve skeletally mature cynomolgus monkeys. Defects were
      treated with intermittent passive motion (IPM) or cast-immobilization (CI) for
      two weeks, followed by six weeks of ad libitum cage activity. We measured
      restoration of the articular surface, and the volume, composition, type II
      collagen concentration and in situ material properties of the repair tissue. The
      osteochondral repair response restored a mean of 56% of the FC and 34% of the PA
      articular surfaces and filled a mean of 68% of the chondral and 92% of the
      osseous defect volumes respectively. FC defect repair produced higher
      concentrations of hyaline cartilage (FC 83% vs. PA 52% in chondral defects and FC
      26% vs. PA 14% in osseous defects) and type II collagen (FC 84% vs. PA 71% in
      chondral defects and FC 37% vs. PA 9% in osseous defects) than PA repair. IPM did
      not increase the volume of chondral or osseous repair tissue in PA or FC defects.
      In both PA and FC defects, IPM stimulated slightly greater expression of type II
      collagen in chondral repair tissue (IPM 81% vs. CI 74%); and, produced a higher
      concentration of hyaline repair tissue (IPM 62% vs. CI 42%), but IPM produced
      poorer restoration of PA articular surfaces (IPM 23% vs. CI 45%). Normal
      articular cartilage was stiffer, and had a larger Poisson's ratio and less
      permeability than repair cartilage. Overall Cl treated repair tissue was stiffer
      and less permeable than IPM treated repair tissue. The stiffness, Poisson's ratio
      and permeability of femoral condyle cast immobilized (FC CI) treated repair
      tissue most closely approached the normal values. The differences in
      osteochondral repair between FC and PA articular surfaces suggest that the
      mechanical environment strongly influences the quality of articular surface
      repair. Decreasing the risk of post-traumatic osteoarthritis following intra
      articular fractures will depend on finding methods of promoting the osteochondral
      repair response including modifying the intra-articular biological and mechanical
      environments.

PMID- 14575254
TI  - Tendon creep is potentiated by NKISK and relaxin which produce collagen fiber
      sliding.
AB  - The pentapeptide NKISK has been reported to inhibit the binding of decorin, a
      proteoglycan on the surface of collagen fibrils, to fibronectin, a tissue
      adhesion molecule. Relaxin has been shown to be effective in relaxing ligaments
      and other connective tissues. Through collagen staining studies, we have
      previously demonstrated that collagen fiber sliding is important during changes
      in ligament length. Because of our interest in fibril-fibril binding as it
      relates to changes in length of tendon or ligament, we investigated the potential
      of NKISK, relaxin, or both in combination to potentiate creep. We suspended
      stained rat tail tendons in test solutions under a constant stress and observed
      length changes and subsequent collagen fiber sliding. Both NKISK and relaxin
      potentiated rat tail tendon creep with changes in length most likely occurring as
      a result of collagen fiber sliding as evidenced by photomicrography.

PMID- 14575255
TI  - Internet use by patients in orthopaedic surgery.
AB  - This study evaluated Internet use among orthopaedic patients in a private
      practice general orthopaedic setting. Of 201 participants, 45% had used the
      Internet either personally or thru a surrogate to search for information about
      their orthopaedic condition. Utilization of the Internet was significantly higher
      than that reported for a community orthopaedic practice surveyed in 1998,
      suggesting that utilization by orthopaedic patient populations mirrors the
      increasing societal use for health information. Most users in this study employed
      multiple search strategies, including using search engines and sites recommended
      by others. The majority of users found medical information on Internet sites to
      be useful and accurate. The number one choice for reconciling conflicting
      information was to ask a physician or a nurse. Most users and non-users reported
      that they would recommend the Internet to others as a source for medical
      information. We recommend several strategies for orthopaedic surgeons to stay
      abreast of these changes and to utilize Internet Patient education resources to
      their own advantage.

PMID- 14575256
TI  - The effect of the internet in the treatment of congenital idiopathic clubfoot.
AB  - Parents have traditionally relied on health care professionals for advice and
      treatment for most orthopaedic conditions, including clubfoot. However, the
      unprecedented access to health care information offered by the Internet is
      changing how parents gather information and make treatment choices. This study
      was designed to evaluate the effect of the Internet in the treatment of clubfoot.
      We performed a retrospective review of the clinical census, statistics of the
      Virtual Hospital web pages on clubfoot, web sites, and web based support-groups
      related to clubfoot from 1995 to 2002. There were 157 patients that came to our
      clinic for treatment, a dramatic increase compared to previous years. There were
      a total of 790,084 hits to the Virtual Hospital web pages, with information
      requested from all states and 72 countries. Interestingly, the referrals also
      changed with patients coming from 30 states and 8 different countries, compared
      to previous years when the majority came from our own state. In addition, 75% of
      the patients were self-referred, many of them while on treatment at outside
      institutions. There were 160 web sites providing information on clubfoot and 5
      large support groups. There were approximately 30,000 messages (average 1000
      messages/month) posted into the support clubfoot websites. After visiting
      Internet support groups, 125 parents transferred or initiated the care of their
      children to a doctor practicing the Ponseti method. In conclusion, the Internet
      provides a mean for parents to obtain disease-specific information in a timely
      manner. Parents used the support-groups to find and proffer information, share
      experiences and opinions, and provide encouragement. This sharing of information
      is affecting how parents make their treatment choices and also has the potential
      to induce unexpected changes in clinical orthopaedic practice.

PMID- 14575257
TI  - Of hedgehogs and hereditary bone tumors: re-examination of the pathogenesis of
      osteochondromas.
AB  - The osteochondroma is a common, benign, primary tumor of bone. A mechanism for
      its pathogenesis has not been identified, but loss of function of EXT genes is
      implicated in sporadic and hereditary multiple osteochondromas. Recent advances
      in the understanding of other molecular signaling pathways in the physis cast
      doubt on the latest pathogenetic theories. These advances are reviewed and used
      as the basis for a revised theory for pathogenesis: A clone of proliferating
      chondrocytes without functional EXT1 (or EXT2) expression fails to produce
      heparan sulfate; lack of heparan sulfate at the cell surface disrupts fibroblast
      growth factor signaling and Indian hedgehog diffusion, leading to focal
      overproliferation and adjacent bone collar deficiency, respectively; together
      these effects are proposed to contribute to osteochondroma pathogenesis.

PMID- 14575258
TI  - Complete arcuate foramen precluding C1 lateral mass screw fixation in a patient
      with rheumatoid arthritis: case report.
AB  - Case report of a complete arcuate foramen in a human atlas vertebra inhibiting
      the placement of lateral mass screw instrumentation at C1. Our objective is to
      report the presentation of the case, the operative considerations, and the
      management for this anatomic variation. The groove for the vertebral artery on
      the posterolateral surface of the atlas (C1) varies in size and depth from a
      slight impression to a clear sulcus. With anomalous ossification the sulcus can
      be bridged which results in a posterolateral tunnel within the posterior arch of
      the atlas. With increasing rates of screw fixation instrumentation that include
      the atlas, it is of paramount importance to know the location and course of the
      vertebral artery in relation to the planned route of instrumentation. The patient
      underwent a posterolateral fusion from C1 to C4 using autogenous iliac crest bone
      graft. Internal fixation from C2 to C4 was obtained using lateral mass screw
      instrumentation. After the vertebral artery was identified passing through the
      posterior arch of C1, sublaminar wires were utilized for fixation from C1 to C2.
      The patient responded well to surgical intervention without complications.
      Abnormal vertebral artery coursing through a posterolateral tunnel in the
      posterior arch of C1 has been described and its incidence has a range from 1.14%
      to 18%. When this variant is present, lateral mass screw fixation at C1 may be
      contra-indicated. We recommend close scrutiny of preoperative radiographs to
      avoid the possibility of endangering the vertebral artery when this situation
      exists.

PMID- 14575259
TI  - Aneurysmal bone cyst following tibial fracture: a case report.
AB  - A 14 year-old boy developed a tibial aneurysmal bone cyst (ABC) following a
      closed tibia fracture. The tumor formed in a site remote from the fracture and
      was not radiographically apparent until one year following the traumatic event.
      Most ABC's present due to fracture or pain, but this lesion was discovered during
      routine follow up films of the tibial shaft fracture. This case lends support to
      the debated theory that ABC's are reactive bone lesions and provides a rare
      radiographic glimpse at the lesion's early rate of development.

PMID- 14575260
TI  - An assessment of the biological fixation of a retrieved Mayo femoral component.
AB  - Implant analysis was conducted on a retrieved Mayo femoral prosthesis that has a
      non-anatomic design with two distinct surfaces intended for osseous fixation. The
      prosthesis itself has a circumferential grit-blasted region interposed with the
      porous surfaces and involving the entire proximal stem. In addition, there are
      pads of mesh porous coating on the anterior, posterior, and medial surfaces
      proximally. A single, radiographically stable stem retrieved after 18 months
      secondary to recurrent dislocations was examined for osseous fixation by
      measurement of trabecular bone into the porous-coated and onto the grit-blasted
      surfaces of the stem. Results showed 17% +/- 7% bone ingrowth into the porous
      coated areas and 20% +/- 16% osseointegration onto the grit-blasted surfaces.
      These results are similar to percentages of ingrowth seen with more conventional,
      anatomic design prostheses.

PMID- 14575261
TI  - The Vienna heritage of Iowa orthopaedics.
AB  - Strong traditions of basic research, clinical innovation, teaching and
      integrating science and evaluation of outcomes into clinical practice have
      characterized University of Iowa orthopaedics for ninety years. These traditions
      were brought to Iowa City from Vienna when Iowa City was a town of fewer than
      10,000 people in a sparcely populated rural state. In the last third of the 19th
      century, surgeons at the University of Vienna, led by Theodore Billroth (1829
      1894), helped transform the practice of surgery. They developed new more
      effective procedures, analyzed the results of their operations, promoted the
      emergence and growth of surgical specialties and sought understanding of tissue
      structure, physiology and pathophysiology. Their efforts made Vienna one of the
      world's most respected centers for operative treatment, basic and clinical
      research and surgical education. Two individuals who followed Billroth, Eduard
      Albert (1841-1900) and Adolf Lorenz (1854-1946) focussed their research and
      clinical practice on orthopaedics. Their successes in the study and treatment of
      musculoskeletal disorders led one of their students, Arthur Steindler (1878
      1959), a 1902 graduate of the Vienna Medical School, to pursue a career in
      orthopaedics. Following medical school, he worked in Lorenz's orthopaedic clinic
      until 1907 when he joined John Ridlon (1852-1936) at the Chicago Home for
      Crippled Children. In 1910, Steindler became Professor of Orthopaedics at the
      Drake Medical School in Des Moines, Iowa, and, in 1913, John G. Bowman, the
      President of the University of Iowa, recruited him to establish an orthopaedic
      clinical and academic program in Iowa City. For the next third of a century he
      guided the development of the University of Iowa Orthopaedics Department, helped
      establish the fields of orthopaedic biomechanics and kinesiology and tirelessly
      stressed the importance of physiology, pathology and assessment of the outcomes
      of operations. From the legacy of Billroth, Albert and Lorenz, Arthur Steindler
      created an internationally recognized center for orthopaedic care, research and
      teaching in Iowa City.

PMID- 14575263
TI  - The suspicious demise of Amy Robsart.

PMID- 14575262
TI  - Iowa and Eugene, Oregon, orthopaedics.
AB  - Over the last 50 years, the commitment of orthopaedic surgeons to basic and
      clinical research and evaluation of treatment outcomes has made possible
      remarkable improvements in the care of people with injuries and diseases of the
      limbs and spine. A group of Oregon orthopaedic surgeons has had an important role
      in these advances, especially in the orthopaedic specialties of sports medicine
      and hip reconstruction. Since Don Slocum (Iowa Orthopaedic Resident, 1934-1937),
      started practice in Eugene, Oregon, in 1939, three orthopaedic surgeons, Denny
      Collis, Craig Mohler and Paul Watson, who received their orthopaedic residency
      education at the University of Iowa, and three orthopaedic surgeons, Stan James,
      Tom Wuest and Dan Fitzpatrick, who received their undergraduate, medical school
      and orthopaedic residency education at the University of Iowa, have joined the
      group Dr. Slocum founded. These individuals, and their partners, established and
      have maintained a successful growing practice that serves the people of the
      Willamette valley, but in addition, they have made important contributions to the
      advancement of orthopaedics.

PMID- 14575264
TI  - [Obituary for Professor emeritus Dr. Erich Lindner].

PMID- 14575265
TI  - Plasticity of synaptic ribbons of the rat pineal gland in vitro--minor effects of
      electrical stimulation.
AB  - Synaptic ribbons (SRs) of mammalian pinealocytes exhibit day/night changes in
      number and size, changes that are apparently regulated by the suprachiasmatic
      nucleus via postganglionic sympathetic nerve fibres. Since the neural control of
      SR changes is far from clear and as pinealocytes produce action potentials, we
      undertook to investigate whether electrical stimulation affects SR changes.
      Isolated rat pineal glands removed during the daytime were kept in vitro for 0,
      30, 60, 90 or 120 min, with or without continuous electrical stimulation (1 mA, 1
      Hz), followed by the quantification of SR profiles (SRPs) by transmission
      electron microscopy. SRs were categorised as to whether they lay less than 100 nm
      away from the pinealocyte plasmalemma (SRPs(near)) or more distant from it
      (SRPs(dist)) and the lengths of the profiles were measured. Cultured pineal
      organs showed a significant numerical depression of SRPs(near), irrespective of
      whether the organs had been electrically stimulated or not. SRPs(near) length
      revealed a significant increase at 60 min in unstimulated control tissue and at
      30 min in electrically stimulated glands. SRPs(dist) length decreased
      significantly at 30 min in control glands and after 60 min in electrically
      stimulated glands. Thus, action potentials inside the pineal gland appear to be
      minor factors regulating SR numbers. In future pineal studies, SRPs(near) and
      SRPs(dist) should be considered separately as they differ in plasticity.

PMID- 14575266
TI  - Origin-associated features of chondrocytes in mouse Meckel's cartilage and costal
      cartilage: an in vitro study.
AB  - Using a cell culture method, we histochemically and immunohistochemically
      investigated whether chondrocytes deriving from different origins, such as
      Meckel's or costal cartilages, express similar phenotypic characteristics.
      Chondrocytes isolated enzymatically from Meckel's and costal cartilages of 17-day
      embryonic mice both actively proliferated and formed cartilage nodules consisting
      of toluidine blue-positive proteoglycans and type II collagen. Both deposited
      calcified cartilaginous matrix as revealed by alkaline phosphatase (ALPase)
      activity and alizarin red staining throughout 3 weeks in culture. Immunostaining
      for osteopontin (OP), osteocalcin (OC), and osteonectin (ON) revealed that
      chondrocytes from both cartilages were positive for their proteins, but type I
      collagen was detected only in cells transforming from Meckel's chondrocytes late
      in the culture. Electron microscopy demonstrated that although costal and
      Meckel's chondrocytes had typical chondrocytic features during 2 weeks in
      culture, Meckel's chondrocytes transformed into osteocytic cells that produced
      thick, banded type I collagen fibrils. In contrast, costal chondrocytes
      maintained typical hypertrophic morphology throughout the final stage of culture.
      The present study suggests that Meckel's chondrocytes derived from neural crest
      ectomesenchyme retain osteogenic potential, and differ from costal chondrocytes
      originating from mesoderm.

PMID- 14575267
TI  - Development of the peritoneal lymphatic stomata and lymphatic vessels of the
      diaphragm in mice.
AB  - The generation and development of the peritoneal lymphatic stomata (PLS) and
      lymphatic vessels of the diaphragm were studied in mice at gestational ages from
      the embryonic to the postnatal period with TEM, SEM and enzyme histochemistry and
      the PLS data were quantitatively analyzed with computer-assisted image processing
      technology (Elescope image analysis software). The results showed that the
      diaphragmatic mesothelium was covered only by flattened mesothelial cells (FMC)
      at the 13th embryonic day (ED 13). At ED 15, some cuboidal mesothelial cells
      (CMC) and immature lymphatic stomata (NLS) were found scattered on the
      diaphragmatic mesothelium. The sub-peritoneal lymphatic capillaries did not
      appear until ED 18. However, no absorptive function was observed in NLS when
      trypan blue granules were injected into the peritoneal cavity. At postnatal day 1
      (PND 1), the endothelial cytoplasm processes of the diaphragm lymphatic
      capillaries span the connective tissue fibers and the basal membrane of CMC to
      form the subperitoneal channels. These channels were connected with NLS and serve
      as the absorptive route between the peritoneal cavity and the sub-peritoneal
      lymphatic vessels. The trypan blue absorption test demonstrated that postnatal
      PLS possessed an absorptive function and had transformed to mature lymphatic
      stomata (MLS) by PND 1. Thus, NLS were renamed of MLS. At PND 5, the cuboidal
      mesothelial cell ridge (CMCR) appeared with increased CMC areas. At PND 10, CMCR
      were fused to form the band-like CMC area with much more MLS distributed in the
      muscular portion of the diaphragm. With distribution area and density of PLS
      increasing and growth of lymphatic vessels, an increased absorptive function from
      the peritoneal cavity was observed in the experiment.

PMID- 14575268
TI  - Morphological analysis and chemical content of natural dentin carious lesion
      zones.
AB  - Dentin is one of the earliest bio-mineralization products to appear in the
      evolution of vertebrates. Dentin reactions to infection mimic earlier
      phylogenetic patterns, and carious lesions are divided into different zones which
      reflect the natural patho-morphological reaction of dentin to the carious attack.
      It was the aim of this study to investigate deep dentin carious lesions of human
      molars with combined polarization light microscopy, scanning electron microscopy
      and energy dispersive X-ray element analysis (EDX) for the determination of
      different zones of the carious lesions, their extent and the chemical content.
      Sixteen extracted teeth with deep dentin carious lesions were embedded in
      Technovit 9100 (Kulzer) and serial sections of 80 microm thickness were made.
      These sections were then examined with polarized light microscopy to identify the
      different zones of the lesions. The outlines of the zones were traced
      consecutively and 3D-reconstructions were made for the determination of the
      extent and calculation of the volumes of the different zones. From the volumes of
      the demineralizing dentin and the translucent zone a Dentin Demineralization
      Index (DDI) was calculated. Three sections of each lesion were then coated with
      carbon and studied with a scanning electron microscope. 3D-reconstruction of the
      teeth showed the rather stable translucent zone, interrupted by remnants of dead
      tracts, and very different volumes of demineralizing dentin. Therefore, with
      increasing size of the demineralizing dentin, the DDI increased. The chemical
      content was measured using energy dispersive X-ray analysis (EDX) in areas of
      intertubular dentin. The content of Ca, P, and C was significantly different in
      all zones. The Ca/P ratio was significantly different between sound dentin and
      demineralizing dentin. From the results we conclude that the mineral content of
      intertubular dentin of the translucent zone and demineralizing dentin is
      different from that of sound dentin, and the unique mineralization pattern of the
      translucent zone is a biological reaction to the carious attack. Because active
      dentin lesions exhibit many non-occluded open dentin tubules, further bacterial
      invasion or, in case of dentin treatment, the penetration of bonding agents
      towards the pulp is morphologically not prevented and therefore of clinical
      importance.

PMID- 14575269
TI  - Crocodilian bone-tendon and bone-ligament interfaces.
AB  - We investigated bone-tendon (27 sites) and bone-ligament (12 sites) interfaces in
      six pairs of crocodile limbs and girdles under light microscopy. These
      crocodilian interfaces often included a direct, unmediated insertion in which the
      tendon or ligament fibers inserted directly into the bone itself without
      fibrocartilaginous mediation. This was quite different from the usual direct
      insertion known in mammals and lizards. Fibrocartilaginous tissue at the bone
      tendon interface is generally believed to protect tendon fibers against shear
      stress. Other types of insertions were found in the crocodilian epiphyses,
      namely, hyaline cartilage and pseudofibrocartilaginous insertions. Notably, a
      thick periosteum/perichondrium and subchondral layer was involved at both
      interfaces. The thick periosteum/perichondrium seemed to form along the
      epiphyseal hyaline cartilage and might function in replacement of
      fibrocartilaginous tissues. Crocodilian thick periosteum/perichondrium would be
      expected to reinforce the limb and girdle bones--especially their epiphyses, in
      which secondary centers of ossification are absent. The subchondral layer--a kind
      of fibrocartilaginous tissue--seemed to play the role of the growth plate in
      compensating for the absence of secondary centers of ossification. Therefore, we
      hypothesized that the crocodile-specific bone-tendon interfaces were the result
      of these specializations of bone development and growth. In crocodiles, the
      disadvantages of the single ossification center are effectively compensated for
      by specialized morphologies, including these interfaces. Specialized bone growth
      provides the crocodile with the largest body size of the recent reptiles and an
      extremely fast method of locomotion.

PMID- 14575271
TI  - Macro- and microstructural organization of the rabbit's celiac-mesenteric
      ganglion complex (Oryctolagus cuniculus).
AB  - The macro- and microstructures of the rabbit celiac-mesenteric ganglion complex
      are described in 20 young animals. We found ten celiac ganglia, twenty-seven
      cranial mesenteric ganglia and eleven celiac-mesenteric ganglia. The celiac
      ganglia had a rectangular shape in nine cases (90%) and a circular one in one
      case (10%). The cranial mesenteric ganglia presented triangular (66.7%),
      rectangular (11.1%), L-shape (18.5%) and semi-lunar (3.7%) arrangements. The
      celiac-mesenteric ganglia were organized in three patterns: a single left celiac
      mesenteric ganglion having a caudal portion (72.7%); celiac-mesenteric ganglia
      without a caudal portion (18.2%) and a single celiac-mesenteric ganglion with two
      portions: left and right (9.1%). The microstructure was investigated in nine
      celiac-mesenteric ganglia. The results showed that the celiac-mesenteric ganglion
      is actually a ganglion complex constituted of an agglomerate of ganglionic units
      separated by nerve fibers, capillaries and septa of connective tissue. Using the
      semi-thin section method we described the cellular organization of the celiac
      mesenteric ganglion complex. Inside of each ganglionic unit, there were various
      cell types: principal ganglion neurons (PGN), glial cells (satellite cells) and
      SIF cells (small intensely fluorescent cells or small granular cells), which are
      the cytologic basis for each ganglionic unit of the rabbit's celiac-mesenteric
      ganglion complex.

PMID- 14575270
TI  - Masticatory function and properties of masseter muscle fibers in microphthalmic
      (mi/mi) mice during postnatal development.
AB  - It is well known that teeth do not erupt in microphthalmic (mi/mi) mice, a type
      of osteopetrotic mice, due to bone resorption failure. Therefore, we surmise that
      the masticatory function of these mice is different from that of normal mice. In
      this study, the differences to the properties of masseter muscle fibers were
      clarified morphologically and immunohistochemically in the mi/mi and normal mice.
      Morphological observations revealed that the muscle fibers in the mi/mi mice were
      smaller than those in normal mice at 9 weeks of age. However, no marked
      differences between mi/mi and normal mice at 2 and 4 weeks of age.
      Immunohistochemical observations showed myosin heavy chain (MHC) slow type
      fibers, which were usually seen at only early stages of development, in 4-week
      old mi/mi mice. There were also differences in isoform compositions between the
      mi/mi and normal mice. These results suggest that differences in masticatory
      function affect the properties of its muscle fibers.

PMID- 14575272
TI  - Topographic morphology and age-related analysis of the neuronal number of the rat
      intracardiac nerve plexus.
AB  - The study was designed to determine the three-dimensional organization of the rat
      intrinsic cardiac neural plexus (ICNP) and to ascertain whether the rat heart
      undergoes a decrease in neuronal number with aging as has been reported for other
      mammalian species, including human. Juvenile (3-4 weeks of age, n = 14) and adult
      (more than 2 months of age, n = 23) animals were examined using enzyme
      histochemistry for acetylcholinesterase in order to visualize the ICNP in total
      hearts. The number of intrinsic cardiac neurons was estimated by counting nerve
      cells in serial sections of the atrial pieces stained with cresyl fast violet.
      The total number of intrinsic cardiac neurons in old rats was 6576 +/- 317. The
      juvenile animals contained significantly fewer such neurons, only 5009 +/- 332.
      Approximately 70% of all intracardiac neurons were amassed within the heart
      hilum, while 30% of the neurons were distributed epicardially. Within the
      interatrial septum, only 11 +/- 11 neurons were identified in the juvenile and 6
      +/- 4 neurons in old rats. Extrinsic nerves entered the rat heart in both the
      arterial and venous parts of the cardiac hilum. The nerves from the arterial part
      of the cardiac hilum extended directly to the ventricles but the nerves from the
      venous part of the hilum formed a particular nerve plexus of the cardiac hilum on
      the heart base. Within the rat epicardium, intrinsic nerves clustered into six
      routes by which they selectively projected to different atrial and/or ventricular
      regions. In conclusion, this study provides a detailed description of the three
      dimensional organization of the rat ICNP and contradicts the decrease in neuronal
      number with aging in the rat heart.

PMID- 14575273
TI  - Systematic study of the internal iliac artery in llama (Lama glama).
AB  - The aim of this research was to determine the origins of the parietal and
      visceral branches of the internal iliac artery of the llama and to match those
      with the known types and classifications in the human being and domestic animals.
      The internal iliac artery divides at the level of the third sacral vertebra into
      the caudal gluteal and internal pudendal arteries corresponding to an
      intermediate long iliac type. It gives off the following collateral branches:
      umbilical, cranial gluteal, obturator and iliolumbar arteries. The intrapelvic
      visceral branches, vaginal or prostatic arteries, arise from the internal
      pudendal artery as occurs in carnivores. This is an important difference in
      relation to the distribution in characteristic long iliac and artiodactyla types.
      The origins of the parietal and visceral branches of internal iliac artery in the
      llama have characteristics in common with the domestic cat, which belongs to the
      carnivores. In relation to the Adachi classification, the internal iliac artery
      of the llama will be included in the IVa type. We believe that this study is a
      contribution of a new aspect in teaching and research in comparative anatomy.

PMID- 14575274
TI  - Sex-related differences in procarbazine-induced cleft palate and microgenia and
      the anti-teratogenic effect of prenatal folic acid supplementation in rats.
AB  - Sex-related differences in the frequency of cleft palates and microgenia in rat
      fetuses prenatally treated with procarbazine (200 mg/kg on day 14 of gestation
      (GD14), group 1), and the anti-teratogenic effect of prenatal folic acid
      supplementation (4 mg/kg on GD14 through GD17, group 2) were studied in LEW.1A
      rats. In group 1, complete clefts were observed in 69% of the male and in 36% of
      the female fetuses while incomplete clefts (present only in the hard palate) were
      exhibited by 31% of the males and 43% of the females. Microgenia occurred in all
      males but only in 64% of the female fetuses. In group 2, the prenatal folic acid
      supplementation significantly reduced the occurrence frequency of complete clefts
      to 9% in males and to 0% in females. In contrast, incomplete clefts increased to
      82% in males and 91% in females. Microgenias were reduced to 73% and 57% in male
      and female fetuses, respectively. Since incomplete clefts present in the hard
      palate are assumed to be residues of spontaneous intra-uterine repair processes
      of exogenously induced complete palatal clefts, we conclude that prenatal
      supplementation with folic acid at a dose of 4 mg/kg promotes the intra-uterine
      repair of cleft palates and offers a partial protection against procarbazine
      teratogenicity. Furthermore, it is deduced that gender-specific differences exist
      in the susceptibility to procarbazine and in the anti-teratogenic effect of folic
      acid on procarbazine-induced microgenia.

PMID- 14575275
TI  - The human digastric muscle: patterns and variations with clinical and surgical
      correlations.
AB  - The digastric muscle is located in the suprahyoid region on each side and
      frequently exhibits two muscular bellies (anterior and posterior) linked by an
      intermediate tendon. The paired digastric muscles act together either depressing
      the mandible or elevating the hyoid bone; therefore acting as a single muscle
      with important physiological roles. In the present study, the digastric muscle
      has been analyzed bilaterally in 74 adult human cadavers. A computerized
      morphometrical investigation of the digastric muscles has been performed (Image
      Pro Plus software package, Media Cybernetics, USA) and the resulting quantitative
      data have been statistically assessed (SPSS 11.0 for Windows, USA). We hereby
      propose an original morphological classification that encompasses five types (I
      V) for the anterior belly (AB); three types (I-III) for the intermediate tendon
      (IT); and two types (I-II) for the posterior belly (PB) of the human digastric
      muscle. In each digastric muscle, the aforementioned anatomical types have been
      characterized according to the muscular bellies and intermediate tendon.
      Consequently, as a result of the combinations of those diverse types, individual
      digastric muscles have been considered as pertaining to distinctive morphological
      patterns (named from A to J). Cases with absence of either AB or PB have been
      included in patterns K and L and would be more appropriately defined as
      monogastric muscles. This innovative classification provides clear-cut anatomical
      parameters for interpreting morphological variants of the digastric muscle with
      relevant clinical and surgical correlations.

PMID- 14575276
TI  - The influence of wisdom tooth impaction on root formation.
AB  - The development of wisdom teeth occurs within a definite period of time. The
      correlation of wisdom tooth development and chronological age has been frequently
      used for several purposes, e. g. the start of orthodontic treatment, estimates of
      age or, for legal and anthropological purposes. Wisdom teeth are frequently
      impacted in the bone. It has been argued that the impaction of wisdom teeth can
      cause a delay in root development. This thesis could have bearing on age
      estimations in teenagers and young adults and the timing of dental treatment. The
      aim of this study was to determine whether the impaction of wisdom teeth
      influences the velocity of root formation. MATERIAL AND METHODS: The dental x
      rays (orthopantomograms) of 1053 outpatients were evaluated (age: 14 to 24
      years). The condition "impacted" or "not impacted" was registered for each wisdom
      tooth present. The impaction types were further classified. The data were then
      calculated using statistical tools. RESULTS: The correlation between the
      developmental stages of wisdom teeth and the chronological age is high. However,
      neither any impaction type nor the whole group of retained wisdom teeth showed a
      statistically significant different course of root development compared to the
      root development of non-retained wisdom teeth. DISCUSSION: This study provides
      evidence for the lack of bearing of wisdom teeth topography on the growth stages
      of the dental roots within definite time intervals, based on the evaluation of
      orthopantomograms only. Obviously, the variations of root formation in the
      selected chronological periods are greater than the variations attributable to
      possible periods of delay in root formation of retained wisdom teeth. These
      results could have some importance for the fields of dental anthropology and
      dentistry.

PMID- 14575277
TI  - Effects of manidipine and nifedipine on blood pressure and renal function in
      patients with chronic renal failure: a multicenter randomized controlled trial.
AB  - Several studies suggest the distinctive advantages of ACE-inhibitors and calcium
      channel blockers in protecting the residual renal function in hypertensive
      patients. Pre-clinical and clinical studies have shown rare adverse events in the
      treatment with manidipine, which is commonly used as antihypertensive drug. We
      therefore decided to compare the effects of manidipine and nifedipine, on blood
      pressure, and renal function. One hundred and one hypertensive patients with
      chronic renal failure were randomly assigned to receive either manidipine 20 mg
      daily or nifedipine 60 mg daily, respectively. Patients were assessed every two
      weeks during the active treatment period with the final follow-up after three
      months. The primary endpoint was the achievement of DBP < or = 90 mmHg or a 10
      mmHg DBP reduction from the baseline values, whilst the secondary endpoints was
      the improvement of the renal function assessed through the creatinine clearance,
      creatinine blood levels, protein and sodium urine excretion. Significant
      reduction in SBP (p < 0.001) and DBP (p < 0.001), compared to the baseline
      values, was reached in both treatments. Creatinine blood levels (p < 0.05) and
      creatinine clearance (p < 0.01) significantly increased in the manidipine group.
      Protenuria did not significantly change in the manidipine group but increased in
      the nifedipine group (p < 0.05). The number of patients with severe adverse
      reactions differed significantly (p < 0.01) between the groups with the highest
      frequency for nifedipine (14.5%) compared to manidipine (8.5%). The withdrawal
      rate was not significantly different between the groups. Manidipine is equally
      safe and effective as nifedipine and it may have more activity on renal function
      and less severe side effects compared to nifedipine.

PMID- 14575278
TI  - Attenuation of cyclosporine-induced renal dysfunction by catechin: possible
      antioxidant mechanism.
AB  - One of great use of immunosuppressant, Cyclosporine-A (CsA) is in the solid organ
      transplantation; however the extensive use of this is cautionable due to its
      toxic effect in renal tissue, characterized by the tubular atrophy, interstitial
      fibrosis, and progressive renal impairment. However, there are many mediators are
      associated with pathogenesis of nephrotoxicity of CsA, the exact mechanism is
      still in debate. Recent studies indicate that Reactive Oxygen Species (ROS)
      induced oxidative stress and lipid peroxidations are the important mechanisms
      implicated in the pathophysiology of nephrotoxicity with CsA. In the present
      study we examined effect of dietary flavonoid catechin on oxidative damage in
      cyclosporine-A induced nephrotoxicity. Chronic administration of CsA (20
      mg/kg/day) subcutaneously for 21 days significantly decreased the body weight as
      compared with vehicle treated rats. CsA (20 mg/kg/day) administration for 21 days
      significantly decreased the renal function by increase in the serum creatinine,
      blood urea nitrogen, and decrease in the creatinine and urea clearance as
      compared with vehicle treated rats. Catechin (100 mg/kg/day) for 21 days along
      with CsA significantly reversed the changed renal parameters, however lower dose
      of catechin (50 mg/kg/day) restored only increased serum creatinine levels as
      compared with CsA alone treated group. Biochemical analysis revealed that chronic
      administration of CsA (20 mg/kg/day) for 21 days significantly induced lipid
      peroxidation and decreased the glutathione levels in the kidney homogenate of
      rats. It is also observed that chronic CsA administered rats showed decrease in
      antioxidant defense enzyme superoxide dismutase and increase in the catalase
      activity as compared with vehicle treated rats. Co-administration of catechin
      (100 mg/kg/day) orally along with CsA for 21 days significantly reduced the lipid
      peroxidation and restored the decreased glutathione levels as compared with CsA
      alone group, but lower dose of catechin (50 mg/kg/day) restored only decreased
      glutathione levels induced by CsA. Co-administration of only higher dose of
      catechin (100 mg/kg/day) along with CsA significantly increased the superoxide
      dismutase (SOD) levels as compared with CsA alone treated group. It is also
      observed that catechin (100 mg/kg/day) along with CsA further increased the
      catalase levels as compared with CsA alone treated group, but not with lower dose
      of catechin. Animals administered with catechin (100 mg/kg/day) alone for 21 days
      showed significant increase in the catalase levels as compared with vehicle
      treated group. The major findings of the present study suggest that oxidative
      stress might play a significant role in CsA-induced nephrotoxicity. In
      conclusion, dietary administration of flavonoid catechin could be a useful
      component for the prevention/treatment of CsA-induced nephrotoxicity.

PMID- 14575279
TI  - A longitudinal study of the yield and clinical utility of a specifically designed
      secondary hypertension investigation protocol.
AB  - OBJECTIVE: It has become common practice to use a day-case based approach to
      identify from the population of hypertensive patients those with an identifiable
      cause. We aimed to prospectively identify 96 consecutive hypertensive patients
      undergoing an algorithmic investigation protocol based around two day case
      hospital attendances. METHODS: The overall diagnostic yield and associated costs
      were recorded and the patients were observed for a mean of 2.5 years with
      ambulatory blood pressure (BP) monitoring every three months. RESULTS: A
      secondary cause of hypertension was identified in 18.1% of patients, three
      quarters of whom had renovascular disease. There was a fall in blood pressure
      with time (157/97 vs. 140/85) but this was associated with an increase in the
      amount of medication required (mean medication score 5.99 vs. 7.65). Improvement
      in BP occurred irrespective of whether or not a secondary cause was identified.
      Only 3.2% of patients were cured of their hypertension as a result of enrollment
      in the protocol. The cost of identifying each case of secondary hypertension was
      Euro 10, 196. CONCLUSIONS: A comprehensive protocol aimed at identifying
      secondary hypertension had a low yield, the majority of whom had renovascular
      disease. In light of recent data illustrating the lack of improvement in BP
      following dilatation or bypass of atherosclerotic renovascular disease, it is
      debatable whether searching for it is justifiable.

PMID- 14575280
TI  - Isolation, characterization, and evaluation of metallothionein in renal
      transplant patients.
AB  - The plasma metallothionein concentration was studied in renal transplant
      patients. These patients are submitted to an attack of free radicals catalyzed by
      metals such as copper, zinc, cadmium, and others. The function of metallothionein
      is to bind toxic metals inhibiting the attack of free radicals and oxidative
      stress that patients receiving renal transplants are submitted to. This is the
      reason for studying this protein in this work. The metalloprotein was separated
      from the plasma by thermoprecipitation and molecular exclusion chromatography
      with Sephadex G-75 followed by anionic-ionic exchange chromatographic
      purification with a CINa gradient. Identification was done by SDS electrophoresis
      in acrylamide gel with markers and commercial protein. Finally, determinations
      were made by atomic absorption, silver saturation method. In this work,
      determinations were made in the plasma of 11 patients before and 48 h and 1 and 2
      weeks after renal transplantation. The same study was carried out in parallel in
      a control group of 11 blood donors. The results obtained show the existence in
      the plasma of metallothionein, with lower concentrations in patients than in
      controls (19 +/- 1.2 mg vs. 12 +/- 1.2 mg). The levels were lowest in the patient
      group analyzed 48 h after having received the transplant (6.34 mg) and had
      recovered slightly one and two weeks later.

PMID- 14575281
TI  - Verapamil reverts acute renal functional impairment induced by angiotensin II
      converting enzyme inhibitors.
AB  - Angiotensin converting enzyme inhibitors (ACEI) reduce blood pressure (BP) and
      provide end-organ protection, but may induce renal function deterioration. In
      these cases, serum creatinine (SCr) can be normalized by ACEI withdrawn. In some
      patients, it could be desirable to maintain the ACEI for the protection of the
      kidney and heart. The objective of the study was to evaluate the effect of
      Verapamil (V) on renal function added to patients with elevated SCr due to ACEI
      treatment. In 46 hypertensive patients without previous renal failure, in which
      ACEI treatment induced an acute increase in SCr (> or = 20% or 0.5 mg/dL), ACEI
      treatment was maintained and 180 mg/day of V was added for 12 weeks. Those
      patients showing further SCr increase or no BP control at four weeks were
      withdrawn. Patients under BP control were moved on the combination V 180 +
      Trandolapril 2 mg/day for eight weeks more. SCr decreased from 136 +/- 49
      micromol/L at baseline to 126 +/- 49 at 12 weeks after adding V (p < 0.001) and
      to 111 +/- 31 micromol/L at 20 weeks (p < 0.01). Creatinine clearance increased
      from 62 +/- 22 mL/min at baseline to 68 +/- 28 after 12 weeks of V (p < 0.001).
      This article demonstrates than in patients with acute renal function impairment
      secondary to ACEI treatment, the addition of 180 mg/day of verapamil to ACEI
      reverses SCr towards previous values.

PMID- 14575282
TI  - Extrapulmonary tuberculosis in chronic hemodialysis patients.
AB  - BACKGROUND: The incidence of extrapulmonary tuberculosis is higher in dialysis
      than general population. The aim of the study was to characterize clinical
      picture in dialysis patients, who developed extrapulmonary tuberculosis. METHODS:
      We retrospectively investigated the hemodialysis patients with extrapulmonary
      tuberculosis. 2208 hemodialysis patients were reviewed for extrapulmonary
      tuberculosis from October 1986 to January 2001. RESULTS: Seventeen patients (10
      male, 7 female) were enrolled. The mean age was 57.4 +/- 12.4 years. The sites
      for extrapulmonary tuberculosis were peritoneum (35.3%, 6/17), cervical lymph
      node (17.6%. 3/17), bone marrow (5.9%, 1/17), spine (5.9%, 1/17), knee (5.9%,
      1/17), brain (5.9%, 1/17), pericardium (5.9%, 1/17), cutaneous tissue (5.9%,
      1/17) and genitourinary system (5.9%, 1/17). Fourteen of 15 tissue-biopsy
      specimens from suspicious sites revealed granulomatous inflammation. There were
      low yield in mycobacteria culture (11.1%, 1/9) and PCR (33.3%, 2/6). Three
      patients died during the treatment of the disease. CONCLUSION: Extrapulmonary
      tuberculosis constitutes a major part of tuberculosis in dialysis patients.
      Tissue biopsy with invasive procedures, such as laparoscopy or laparotomy, may be
      necessary if clinical presentations are suspicious.

PMID- 14575283
TI  - Antiphospholipid antibodies in patients with lupus nephritis.
AB  - The aim of this study was to compare the prevalence of anticardiolipin antibodies
      with other types of antiphospholipid antibodies (aPL) (antiphosphatidylserine-
      aPS, antiphosphatidylinositol--aPI, antiphosphatidylethanolamine--aPE) in
      patients with lupus nephritis and to find if the examination of a panel of
      various aPL is valuable for further diagnosis of patients. Additionally we
      determined the levels of autoantibodies against beta2-glycoprotein I (beta2GPI)
      and oxidized low-density lipoprotein (anti-oxLDL) and also investigated the
      relationship between antibodies against beta2GPI and oxLDL, which were assessed
      by ELISA methods. Twenty-two patients with lupus nephritis were studied. The
      control group consisted of 62 healthy blood donors. A statistically significant
      higher occurrence of all aPLs in the patients with lupus nephritis in comparison
      to the control group was found. The prevalence of polyspecific antibodies, which
      reacted with at least two various phospholipids, was 82% in the group of SLE
      patients. Significantly higher levels of IgG anti-beta2GPI in the sera of SLE
      patients (p = 0.0003) was detected. The levels of anti-oxLDL in the sera of the
      patients group did not differ significantly from the control one. Some positive
      samples for anti-beta2GPI and negative for aCL or anti-oxLDL and vice versa were
      found. It ca be concluded that the production of aPL including anti-beta2GPI and
      anti-oxLDL in the lupus nephritis patients is higher in comparison with healthy
      blood donors. We assume that the estimation of various types of aPL may be
      important in the selection of the group patients with renal diseases. The
      synthesis of aPL can reflect the spreading of the autoimmune response for several
      antigens modified on the vessel wall.

PMID- 14575284
TI  - Reduced endothelial factor VIII staining in renal microcirculation correlates
      with hemodynamic alteration in nephrosis.
AB  - Endothelial factor VIII staining in renal microcirculation was performed in eight
      nephrotic patients associated with mesangial proliferation (MesP) and six
      nephrotic patients associated with focal segmental glomerulosclerosis (FSGS). The
      result in MesP revealed a greater staining for glomerular endothelial factor VIII
      (35 +/- 15%) and for postglomerular capillary endothelial factor VIII (65 +/-
      21%) than that observed in FSGS, which revealed a 11 +/- 8% staining for
      glomerular endothelial factor VIII and 19 +/- 15% staining for postglomerular
      capillary endothelial factor VIII. This finding implies that there is a greater
      loss of endothelial cell in renal microcirculation in FSGS. Such a finding
      correlates with the intrarenal hemodynamics which illustrated (Futrakul, P.;
      Sitprija, V.; Yenrusi, S. Glomerular endothelial dysfunction determines disease
      progression: a hypothesis. Am. J. Nephrol. 1997, 17, 533-540.) a mild reduction
      in renal plasma flow (535 +/- 106 mL/min/1.73 m2, normal 600 mL/min/1.73 m2) and
      in peritubular capillary flow (422 +/- 80 mL/min/1.73 m2, normal 480 mL/min/1.73
      m2) in MesP and (Futrakul, P. Coagulation in glomerulonephritis and nephrotic
      symdrome: Its therapeutic intervention. In Asian Manual of Nephrology, Takeuchi,
      T.; Sugino, N.; Ota, K., Eds.; SEAMIC Publication, Tokyo, 1981; pp. 89-95.) a
      greater reduction in renal plasma flow (108 +/- 50 mL/min/1.73 m2) and in
      peritubular capillary flow (87 +/- 42 mL/min/1.78 m2) in FSGS. Therefore the
      study has emphasized both the structural and functional defects of endothelium in
      renal microcirculation in particular in FSGS.

PMID- 14575285
TI  - Hyperhomocystinemia and the prevalence of symptomatic atherosclerotic vascular
      disease in Taiwanese chronic hemodialysis patients: a retrospective study.
AB  - AIM: Hyperhomocystinemia is now recognized as an independent risk factor for
      atherosclerotic cardiovascular disease in patients with normal renal function.
      Hyperhomocystinemia is common in patients with chronic renal failure. This aim of
      this study was designed to look for associations between hyperhomocystinemia and
      clinically symptomatic atherosclerotic vascular disease (ASVD) in Taiwanese
      chronic hemodialysis patients. METHODS: Two hundred patients undergoing
      hemodialysis were enrolled in the study. They had predialysis blood work
      performed for total homocysteine, serum folate, and vitamin B12 levels. A history
      of clinically significant ASVD was elicited using information from the patients'
      questionnaires and verified by careful inpatient and outpatient chart review.
      RESULTS: Mean homocysteine concentration was 29.0 micromol/L overall. A total of
      196 patients had hyperhomocystinemia and were enrolled in this study. ASVD was
      present in 24.5% of patients. The mean homocysteine concentration was 31.9
      micromol/L and 28.7 micromol/L in patients with (n = 48) and without (n = 148)
      ASVD, respectively (P = 0.04). There was association hyperhomocystinemia between
      chronic hemodialysis patients with ASVD and without ASVD. There were significant
      differences including age, homocysteine level, vitamin B12 level and glucose
      intolerance in the two groups (P < 0.05). Plasma homocysteine concentrations
      showed significant positive correlations with serum folate or vitamin B12 in
      majority patients. No patient had serum folate or vitamin B12 deficiency. The
      adjusted odds ratio for atherosclerotic disease was 2.8 (95% CI, 1.109-7.467) for
      those subjects with a homocysteine level in the highest quartile compared with
      the lowest 3 quartiles. CONCLUSIONS: The prevalence of hyperhomocystinemia is 98%
      among hemodialysis patients. There is a significant association between
      hyperhomocystinemia and ASVD in Taiwanese chronic hemodialysis patients. There
      are also associations between homocysteine levels and serum folate/vitamin B12
      levels in the majority of the patients. Clinical trials are needed to determine
      the optimal therapy of folic acid dose for hyperhomocystinemia in Taiwanese
      chronic hemodialysis patients in the future.

PMID- 14575286
TI  - Renal function after cardiac surgery: adverse effect of furosemide.
AB  - Renal failure is a frequent event after cardiopulmonary by-pass. Hemodynamic
      alterations that occur during surgery, as well as factors depending on the host,
      are the main risk factors for renal dysfunction. To evaluate the frequency and
      risk factors for renal dysfunction in this setting, a cohort of fifty patients
      with preoperative serum creatinine under 1.5 mg/dL, submitted to cardiac surgery
      with cardiopulmonary by-pass was analyzed. Variables related to preoperative
      patient condition, intraoperative and postoperative periods were recorded. Renal
      function was assessed by clearances of creatinine, urea and free water, also by
      fractional excretion of sodium (FENa), at baseline, at anesthetic induction and
      during postoperative period. Patients were arbitrarily divided in two groups,
      according to the serum creatinine (S(Cr)) value at the end of the postoperative
      period: Group 1: S(Cr) < 2 mg/dL (n = 44 patients (88.5%)) and Group II: S(Cr) >
      2 mg/dL (n = 6 patients (11.5%)). A decrease of renal function was observed in
      all patients: creatinemia raised from 1.04 +/- 0.2 to 1.55 +/- 0.4 mg/dL (33%),
      associated with a rise in FENa. Differences between group I and group II using
      univariate analysis were: baseline serum creatinine (1.01 +/- 0.23 mg/dL vs. 1.26
      +/- 0.19 mg/dL, p = 0.03), FENa (0.99 +/- 0.8 vs. 2.2 +/- 2.1, p = 0.04),
      furosemide dose during surgery normalized to body surface area (93.2 +/- 23
      mg/1.73 m2 BSA vs. 135 +/- 38 mg/1.73 m2 BSA, p < 0.001), and hemodilution index
      (17.3 +/- 4.3% vs. 22.8 +/- 3.2%, p < 0.01). In the multiple regression model,
      baseline creatinemia and furosemide dose were associated to renal dysfunction.

PMID- 14575287
TI  - Discrepancies in serum albumin measurements vary by dialysis modality.
AB  - BACKGROUND: Serum albumin level is an important prognostic marker in patients
      with chronic renal failure. However there are discrepancies in the methods of
      estimation of serum albumin. The objective of this study is to evaluate the
      magnitude of the discrepancy in the serum albumin levels as measured by
      Bromcresol Green (BCG) and Bromcresol Purple (BCP) dye methods in patients on
      hemodialysis (HD) and peritoneal dialysis (PD) and to ascertain the clinical
      determinants of the discrepancy (deltaSA = BCG-BCP; g/dL) in each of the
      modalities. METHOD: We measured serum and plasma albumin levels by BCG and BCP
      methods in 19 adult HD patients and 18 adult PD patients treated in the dialysis
      units of the University of Colorado Health Sciences Center. Similar measurements
      were performed in 10 normal adult subjects. In all groups, paired blood samples
      were taken to estimate the albumin in both serum and plasma. Nephelometry (NM)
      was subsequently performed on the serum of 13 of the HD patients, 14 of the PD
      patients, and each of the 10 normal subjects. RESULTS: We found that for both the
      dye methods serum and plasma albumin levels are almost identical in each of the
      three subject groups. In the normal subjects serum albumin estimated by BCP is in
      good agreement with NM values but BCG overestimates the albumin levels. In the PD
      group the discrepancy between the BCG and BCP (deltaSA) is statistically
      significant with the BCG averaging 0.59 +/- 0.12 g/dL more than the BCP. The BCG
      values are closer to those obtained by the "gold standard", NM. In the HD group
      the deltaSA is significantly (p < 0.001) less than in the PD group (0.34 +/- 0.11
      g/dL). As for PD, BCG values are closer to NM values. Increasing age, female
      gender, and higher dialysis adequacy are associated with higher deltaSA in the HD
      but not in the PD group. Utilizing linear regression analysis we developed
      equations for each dialysis modality to convert albumin measurements from one
      method to the other. CONCLUSION: We confirm that a discrepancy exists between the
      commonly used dye methods (BCG and BCP) for serum albumin estimation. This
      discrepancy is significantly lower in HD patients than in PD patients.
      Nephrologists should be aware of this discrepancy and appropriate corrections
      should be made during quality improvement analysis.

PMID- 14575288
TI  - Confirming the utility of four kidney biomarker tests in a longitudinal follow-up
      study.
AB  - In this follow-up study, 526 persons were followed for almost 5 years to assess
      the reversibility and predictive value of four kidney biomarkers in a field
      epidemiology setting. This study examined (a) whether elevations in urinary
      albumin, N-acetyl-beta-D-glucosaminidase, retinol-binding protein, and alanine
      aminopeptidase remained elevated at follow-up and (b) whether these initial
      elevations were predictive of kidney disease (as measured by markers of kidney
      dysfunction: serum creatinine, serum cystatin C, creatinine clearance, and urine
      osmolality) at follow-up. Study participants were 8-76 years of age at baseline
      and were followed for an average of 4.5 years. Approximately 50% of adults who
      had an elevated biomarker did not have an elevation at followup. Youths with
      elevated biomarkers at baseline, but who completed adolescence by the time of the
      follow-up, no longer had any elevations in biomarkers at follow-up. Adult
      participants who had elevated biomarkers and selected health conditions at
      baseline (diabetes and, to a lesser extent, heart disease, hypertension, gout,
      and urinary tract disease) were more likely to show early indicators of kidney
      impairment at follow-up. Participants with these health conditions and normal
      kidney biomarker values at baseline had kidney test results at follow-up that
      were similar to results of study participants who did not have these health
      conditions at baseline. The presence or absence of elevated biomarkers at
      baseline among generally healthy participants was not associated with the
      development of early indicators of kidney impairment at follow-up. This
      longitudinal study confirmed the utility of these four kidney biomarker tests as
      markers of preclinical organ dysfunction among adults with certain preexisting
      medical conditions.

PMID- 14575289
TI  - The prevalence and clinical features of tuberculous peritonitis in CAPD patients
      in Turkey, report of ten cases from multi-centers.
AB  - OBJECTIVE: To determine the rate, risk factors and outcome of Tuberculous
      Peritonitis (TBP) in patients treated with continuous ambulatory peritoneal
      dialysis (CAPD) in our units. DESIGN: Retrospectively, we reviewed the medical
      data of all CAPD patients from 12 centers for TBP, covering the period between
      1986 and December 2002. SETTING: All patients were from 12 renal clinics at
      tertiary-care university hospitals. RESULTS: Ten cases of TBP were identified
      among the CAPD patients in our centers. There were five male and five female
      patients with a mean age of 37.2 years. None of the patients had tuberculosis
      history, 6 patients had predominance of PNL. One patient had coincidental
      bacterial peritonitis. Two patients were successfully treated without the removal
      of the Tenckhoff catheter. CONCLUSION: TBP in CAPD patients is a very rare
      complication. In contrast to predominance of lymphocytes in nonuremic patients
      with tuberculous peritonitis, CAPD patients with tuberculous peritonitis may have
      predominance of PNL on examination of the peritoneal fluid. Since TBP has high
      morbidity and mortality, early diagnosis and treatment of disease are extremely
      important for improving outcome.

PMID- 14575290
TI  - Nighttime blood pressure fall in renal disease patients.
AB  - OBJECTIVE: There are controversial reports in the prevalence of abnormal
      nighttime blood pressure fall in renal patients. It has been evaluated nocturnal
      BP in renal patients using 24 h blood pressure monitoring (ABPM) in comparison
      with nontreated control subjects either normotensives or hypertensives. DESIGN
      AND METHODS: It has been reviewed 137 ABPM studies performed in renal patients
      (47.8 +/- 15.4 years, 76 men and 61 women). The control group includes 119
      subjects without kidney disease, 65 were normotensives, and 49 were
      hypertensives, aged 46.8 +/- 12.1 years, 59 men and 60 women. The ambulatory BP
      was measured noninvasively for 24h by the SpaceLabs 90207 device programmed to
      measure BP every 15 min during daytime and every 20 min during nighttime. The
      definition of daytime and nighttime was made on the basis of wakefulness and
      sleep or bed rest periods, obtained from a diary kept by each subject. RESULTS:
      SBP, but not DBP, was higher (133.9/81.7) in renal disease patients when compared
      to nonrenal subjects (127.9/80.8, p < 0.01). When the control group was split
      into normotensive and hypertensive patients there were still significant
      differences, but hypertensives had higher BP than renal disease patients
      (139.0/89.7, p < 0.05). Nocturnal SBP fall in renal disease patients was reduced
      (5.8%, p < 0.001) and so was DBP fall (11.1%, p < 0.001) compared with the
      overall nonrenal patients sample (SBP 10.8; DBP 15.3%). The frequency of
      nondipper status in renal disease patients (39.6%) was higher than in control
      patients (18.4%, p < 0.001). Nontreated normotensive renal disease patients did
      not show any difference in either SBP or DBP nighttime fall with respect to
      control normotensives. Neither do nontreated hypertensive renal patients as
      compared with control hypertensives. There were not differences between
      proteinuric and nonproteinuric patients in nocturnal BP fall. The same result was
      obtained when hypertensive and normotensive nontreated renal patients were
      compared. The presence of renal failure did not induce a reduction of nocturnal
      BP fall. Most of treated renal patients were mainly receiving drug therapy during
      the morning and frequently this was the single daily dose. CONCLUSIONS: Altered
      diurnal rhythm should not be considered as a usual complication of renal disease.
      Inadequate antihypertensive pharmacotherapy could be related to the abnormalities
      of nighttime BP fall when it is detected.

PMID- 14575291
TI  - Treatments of hemodynamic maladjustment and oxidative stress prevent renal
      disease progression in chronically severe glomerulonephritides.
AB  - Hemodynamic maladjustment is a unique observation in chronically severe
      glomerulonephritides. It is characterized by a markedly elevated efferent
      arteriolar resistance (RE), an elevated intraglomerular hydrostatic pressure (PG)
      and a markedly decreased renal plasma flow (RPF), and peritubular capillary flow
      (PTCF). A correction of such hemodynamic maladjustment can be accomplished by
      administering a combination of vasodilators (angiotensin receptor antagonist,
      angiotensin converting enzyme inhibitor, and calcium channel blocker) in 14
      chronic glomerulonephritides with severe renal function impairment (mean serum
      creatinine 3.6 + 1.3 mg/dL). Doses titration aim for maximal renal perfusion
      effect (increased RPF, PTCF) or maximal renal function improvement (increased
      CCr, reduced FE Mg) usually higher than needed for maximal blood pressure
      reduction. Evidence of oxidative stress is also corrected with high doses of
      vitamins C and E. After a mean period of treatment for 13.5 months, improvements
      in CCr (pre R(x) 22 +/- 10 vs. post R(x) 32 +/- 13 mL/min/1.73 m2), and FE Mg
      (pre R(x) 11.9 +/- 4% vs. post R(x) 10 +/- 3%) were observed in conjunction with
      the improvement in intrarenal hemodynamics namely RPF (pre R(x) 201 +/- 71 vs.
      post R(x) 288 +/- 99 mL/min/1.73 m2), PTCF (pre R(x) 161 +/- 57 vs. post R(x) 242
      +/- 90 mL/ min/1.73 m2), PG (pre R(x) 56.7 +/- 0.5 vs. post R(x) 51 +/- 0.1 mm
      Hg), and RE (pre R(x) 12085 +/- 6503 vs. post R(x) 6550 +/- 1872 dyne.s.cm(-5)).

PMID- 14575292
TI  - Heart rate variability, left ventricular functions, and cardiac autonomic
      neuropathy in patients undergoing chronic hemodialysis.
AB  - OBJECTIVE: Autonomic neuropathy and impairment of left ventricular functions
      (LVF) have been frequently encountered in chronic renal failure (CRF). The aim of
      the present study was to evaluate the relationship of cardiac autonomic
      modulation impairments, as assessed by means of heart rate variability (HRV),
      with clinical characteristics, and left ventricular function in the patients with
      CRF undergoing hemodialysis (HD). METHODS: Twenty control subjects (Group I) and
      22 comparable by age and gender patients with CRF undergoing hemodialysis (Group
      II) were enrolled in the study. After routine clinical and biochemical
      evaluations, electrocardiography, and 2 Dimensional, M Mode echocardiography were
      performed in all participants. Frequency domain HRV analysis was studied by using
      Kardiosis System. The powers (P1 and P2) and the central frequencies (F1 and F2)
      of low and of high frequency spectral bands were recorded. RESULTS: End systolic
      (ESV) and end diastolic volumes (EDV) were significantly higher in Group II (59.3
      +/- 21.1mL vs. 34.0 +/- 14.3 mL and 131.5 +/- 37.3 mL vs. 96.9 +/- 18.9 mL, p <
      0.01, p < 0.05, respectively) when compared to those of Group I. Ejection
      fraction (EF) and fractional shortening (FS) were significantly lower in Group II
      than in control subjects (52.3 +/- 2.4% vs. 63.7 +/- 10.1% and 0.29 +/- 0.01 vs.
      0.34 +/- 0.07, p < 0.001, p < 0.05, respectively). P and P2 were decreased in
      Group II than in Group I (136.2 +/- 173.9 m s2 vs. 911.0 +/- 685.5 and 96.5 +/-
      149.6 vs. 499.7 +/- 679.5, p < 0.001, p < 0.01, respectively). Significant
      correlations were found between high frequency spectral power and dialysis
      duration (DD), ESV, EDV, EF, FS (r = 0.52 p < 0.01, r = 0.68 p < 0.001, r = 0.65
      p < 0.002, r = 0.66 p < 0.02, and r = 0.69 p < 0.01). CONCLUSION: As a result,
      the dependence of cardiac autonomic neuropathy on the disease duration and degree
      of left ventricular function impairment was shown in the patients undergoing
      chronic hemodialysis.

PMID- 14575293
TI  - Continuous renal replacement therapy (CRRT) or intermittent hemodialysis (IHD)-
      what is the procedure of choice in critically ill patients?
AB  - Although at present there is no prospective randomized study which could show
      significantly better survival of patients on continuous procedures, the majority
      of intensivists advocate this technique of renal function replacement due to
      generally accepted opinion that it has less effect on circulation of already
      hemodynamically unstable patients. In our prospective randomized study with 104
      patients, we also did not observe any difference in 28 days survival, in total
      survival, as well as in circulatory instability between two treatment modalities.
      Even in subgroup of 80 patients with sepsis and septic shock there were no
      difference in survival. Sepsis was the underlying disorder in 52 and septic shock
      in 28 patients out of 104 patients analyzed in this study. Our prospective
      randomized study did not show a statistically significant difference between the
      two methods of renal replacement therapy. Survival rates were not affected and
      neither was the occurrence of hemodynamic instability. We believe that both
      methods are complementary; IHD for faster elimination of electrolytes and waste
      products elimination, CRRT for regulation of higher calories requirements and for
      hemodynamically unstable patients. The expectations that one method is superior
      to the other in the term of better survival have not been corroborated by the
      current data available in the literature. The choice of the method should be
      individualized. ARF, which is an integral part of MOF, is a problem frequently
      encountered in critically ill patient treated in the ICU, but outcome of these
      patients depends closely on the control of basic event. Evaluation of each of the
      supportive procedures is therefore hindered by the fact that the underlying
      disease has the crucial effect on survival and the type of supportive procedure
      less so.

PMID- 14575294
TI  - Concurrent renal cell carcinoma and transitional cell carcinoma in a chronic
      hemodialysis patient.
AB  - A 60-year-old female patient had been on maintenance hemodialysis for 12 years
      was suffering from gross hematuria. Subsequent image studies revealed left renal
      and ureteral tumors. She then received left radical nephroureterectomy.
      Histological examination revealed the renal tumor was renal cell carcinoma and
      ureteral tumor was transitional cell carcinoma respectively. To our knowledge,
      this is the first reported case of simultaneous occurrence of these two
      urological cancers in a chronic hemodialysis patient. Our case may imply the
      increased susceptibility of urological malignancy in dialysis patients.
      Physicians should always raise the possibility of urological malignancy when a
      dialysis patient with gross hematuria is encountered. A thorough and careful
      screening for the malignancy should be performed on a regular basis in these
      patients with high risk.

PMID- 14575295
TI  - Axillary artery to contralateral axillary vein graft fistula in chronic
      hemodialysis patients.
AB  - BACKGROUND: Vascular access failure is a severe and common complication for
      hemodialysis patients. The possible vascular access sites are limited in dialysis
      patients. Axillary artery to contralateral axillary vein arteriovenous fistula
      (AVF) is one of the possibilities. However, the clinical outcome of this
      procedure is still un-defined. OBJECT: The purpose of this study is to review the
      clinical outcome of axillary artery to contralateral axillary vein AVF as a
      hemodialysis vascular access. PATIENTS AND METHODS: We retrospectively reviewed
      native or graft arteriovenous fistula records for chronic hemodialysis patients
      at Chang Gung Memorial Hospital in Kaohsiung, Taiwan, from January 1986 to March
      2001. Records were reviewed for all chronic hemodialysis patients, with more than
      2000 individuals receiving more than 10,000 fistulas. Eight patients received
      axillary artery to contralateral axillary vein AVF. RESULTS: The mean age for
      these patients was 61.7 +/- 16.3 year-old at time of surgery. All patients had
      received multiple native or graft arteriovenous fistula creation. The 2-year and
      4-year AVF graft survival is 87.5% and 43.8% respectively. One patients developed
      brachial plexopathy after operation. Another patient had venous hypertension
      distal to the AVF site. Both patients were managed conservatively. There is no
      AVF-related mortality in these patients. CONCLUSION: We conclude that axillary
      artery to contralateral axillary vein graft fistula may be a feasible alternative
      choice for chronic hemodialysis access.

PMID- 14575296
TI  - Bilateral moderate hydroureteronephrosis due to uterine prolapse: two case
      reports and review of the literature.
AB  - Uterine prolapse resulting in hydronephrosis was uncommon. We report two cases of
      complete uterine prolapse and bilateral moderate hydronephrosis. Case 1, she was
      admitted due to fever with pyuria. Uterine prolapse was noted by incidental
      finding. Urine culture showed Escherichia coli. She received total vaginal
      hysterectomy, which corrected the obstruction and bladder dysfunction. Case 2,
      she had a history of liver cirrhosis and was denied further operation due to
      bleeding tendency. Renal echo and intravenous pyelography showed bilateral
      moderate hydronephrosis with hydroureter in the two cases. Normal renal function
      was found in the two cases. We suggest early diagnosis and management are
      necessary in order to prevent renal failure and urinary tract infection.

PMID- 14575297
TI  - Lysophospholipids do not directly modulate Na(+)-H+ exchange.
AB  - Lysophosphatidylcholine (LPC) has been reported to stimulate Na(+)-H+ exchange in
      rat cardiomyocytes. This action may be important in pathological conditions like
      ischemic injury where LPC is generated and Na(+)-H+ exchange activation is an
      important determinant of cardiac damage and dysfunction. It is unclear, however,
      if this stimulation of Na(+)-H+ exchange by LPC occurs through a direct action on
      the exchanger or through stimulation of a second messenger pathway. The purpose
      of the present investigation was to determine if lysolipids could directly affect
      Na(+)-H+ exchange. Purified cardiac sarcolemmal membranes were isolated and Na(+)
      H+ exchange was measured by radioisotopic methods following addition of LPC.
      There were no effects of LPC on Na(+)-H+ exchange at LPC concentrations of < or =
      100 microM at all reaction times examined. Lysophosphatidylethanolamine (LPE),
      lysophosphatidylserine (LPS), lysophosphatidylinositol (LPI) and
      lysoplasmenylcholine (LP(E)C) also did not alter Na(+)-H- exchange at all
      concentrations and reaction times examined. We conclude that any stimulatory
      effects of lysolipids on Na(+)-H+ exchange do not occur through a direct action
      on the exchanger or its membrane lipid environment and must occur through a
      second messenger pathway.

PMID- 14575298
TI  - Antioxidant enzyme gene expression in congestive heart failure following
      myocardial infarction.
AB  - Increased oxidative stress and reduction in antioxidant enzymes have been
      suggested to be involved in the pathophysiology of congestive heart failure
      subsequent to myocardial infarction (MI). The objective of the present study was
      to characterize changes in the mRNA abundance and protein levels for the
      enzymatic antioxidants, superoxide dismutase (SOD), glutathione peroxidase
      (GSHPx) and catalase during the sequelae of congestive heart failure in rats. MI
      was produced by the ligation of the left coronary artery and hearts from controls
      and 1, 4 and 16 week PMI groups were analyzed. Losartan treatment (2 mg/ml in
      drinking water, daily) was started at 4 weeks and continued for 12 weeks. The
      mRNA levels for SOD were reduced by about 40% at 1-week PMI, were near to the
      control levels at 4-week PMI and at 16 weeks PMI, the levels were reduced by
      about 73% below the controls. GSHPx mRNA levels remained unchanged at all time
      points. The mRNA levels for catalase remained unchanged at 1 and 4 weeks PMI and
      were significantly reduced by about 44% at 16 weeks PMI as compared to the
      controls. The protein levels for MnSOD, CuZnSOD, GSHPx at 1 and 16 weeks remained
      unchanged in treated and untreated PMI groups. However, the protein levels for
      catalase was significantly increased in the control and PMI groups treated with
      Losartan. It is concluded that changes in the SOD and catalase activities during
      severe heart failure correlated with changes in mRNA for these enzymes. The
      precise mechanism/s for the improvement in antioxidant reserve and protein levels
      after Losartan treatment is/are unclear at this time.

PMID- 14575299
TI  - Modulation of cardiac remodeling by adenosine: in vitro and in vivo effects.
AB  - The increasing incidence of congestive heart failure has stimulated efforts to
      develop pharmacologic strategies to prevent or reverse the associated process of
      adverse cardiac remodeling. The possibility of utilizing endogenously generated
      factors that are capable of inhibiting this process is beginning to be explored.
      Adenosine, has been described as a retaliatory autacoid with homeostatic
      activities in the regulation of myocardial blood flow, catecholamine release, and
      reduction of injury resulting from periods of ischemia. Adenosine exerts a
      variety of actions that are consistent with the concept that it can reduce or
      inhibit the process of cardiac remodeling. In this manuscript, the basics of
      adenosine metabolism, its cell surface receptors and beneficial actions on the
      cardiovascular system are reviewed. In addition new, in vitro and in vivo data
      will be presented supporting the concept that adenosine exerts actions that may
      ameliorate adverse cardiac remodeling.

PMID- 14575300
TI  - Right ventricular collagen and fibronectin levels in patients with pulmonary
      atresia and ventricular septal defect.
AB  - Pulmonary atresia (PA) with ventricular septal defect (VSD) is an extreme form of
      tetralogy of Fallot with characteristic right ventricular hypertrophy. To reduce
      the right ventricular overload, these children have to undergo staged corrective
      surgery to restore physiological pulmonary perfusion. We studied the degree of
      fibrosis by analysing the myocardial expression pattern (at mRNA and protein
      level) of the extracellular matrix proteins, collagen and fibronectin in biopsies
      taken at corrective surgery from 14 patients affected by PA,VSD. Expression
      analysis by RT-PCR showed significantly higher levels for collagen III (p =
      0.03), whereas collagen Ialpha (p = 0.31) and fibronectin (p = 0.47) mRNA levels
      remained unaltered in PA, VSD patients as compared to age matched controls. Video
      image analysis of immunohistochemical staining showed unchanged interstitial
      levels for total collagen (p = 0.17) as well as for fibronectin (p = 0.13) in the
      patients with PA, VSD. However, peri-vascular staining for collagen (p < 0.01)
      and fibronectin (p = 0.02) represented as the peri-vascular stained area
      corrected for the vessel lumen area showed significantly decreased levels in the
      PA, VSD group as compared to controls. Our results indicate that the patients
      with PA, VSD have inadequate extracellular matrix support for their coronary
      blood vessels and perhaps due to an altered biosynthesis of collagen and
      fibronectin network.

PMID- 14575301
TI  - A mouse model of familial hypertrophic cardiomyopathy caused by a alpha
      tropomyosin mutation.
AB  - Familial hypertrophic cardiomyopathy, a disease caused by mutations in cardiac
      contractile proteins, is characterized by left and/or right ventricular
      hypertrophy, myocyte disarray, fibrosis, and cardiac arrhythmias that may lead to
      premature sudden death. Five distinct point mutations within alpha-tropomyosin
      are associated with the development of familial hypertrophic cardiomyopathy. Two
      of these mutations are found within a troponin T binding site, located at amino
      acids 175 and 180. In this study, we analyze a transgenic mouse model for one of
      the mutations that occur at codon 180: a substitution of a glutamic acid for a
      glycine. These mice develop severe cardiac hypertrophy, substantial interstitial
      fibrosis, and have an increased heart weight/ body weight ratio. Results show
      that calcium-handling proteins associated with the sarcoplasmic reticulum exhibit
      decreased expression. These alterations in gene expression, coupled with the
      structurally-altered tropomyosin, may contribute to the demonstrated decreased
      physiological performance exhibited by these transgenic mice. A DNA hybridization
      microarray analysis of the transgenic vs. control ventricular RNAs shows that 50
      transcripts are differentially expressed by more than 100% during the onset of
      the hypertrophic process, many of which are associated with the extracellular
      matrix. This study demonstrates that mutations within tropomyosin can be severely
      disruptive of sarcomeric function, triggering a hypertrophic response coupled
      with a cascade of alterations in gene expression.

PMID- 14575302
TI  - Analysis of postextrasystolic relaxation response in the human heart.
AB  - Postextrasystolic potentiation is the phenomenon in which ventricular contractile
      force is strengthened by a preceding premature beat. However, the response of
      diastolic function after an extrasystole is unknown. We studied 58 patients with
      chronic heart failure (CHF) and two control subjects to evaluate the response of
      relaxation following extrasystole. At cardiac catheterization, from the
      derivative of the left ventricular (LV) pressure, the ratio of LV peak negative
      dP/dt (-dP/dt) of a postextrasystole to a basal beat was calculated and defined
      as the postextrasystolic relaxation response (PRR). PRR was compared with
      parameters of left ventriculography: LV end-diastolic volume index (EDVI), LV end
      systolic volume index (ESVI), and LV ejection fraction (EF). The PRRs of the two
      control subjects were 0.80 and 0.84. The mean PRR of the CHF patients was 0.99 +/
      0.15. In all subjects, including patients and controls, correlation analysis
      between (EDVI, ESVI, and EF) and PRR yielded the following: (a) EDVI vs. PRR: R =
      0.273, p = 0.036; (b) ESVI vs. PRR: R = 0.446, p < 0.001; and (c) EF vs. PRR: R =
      -0.520, p < 0.001. Thus, normal or non-failing human hearts showed a decline of 
      dP/dt in postextrasystole compared with the basal beats, but failing hearts had
      potentiated relaxation following an extrasystole.

PMID- 14575303
TI  - Differential effects of calpain inhibitors on hypertrophy of cardiomyocytes.
AB  - Two inhibitors of the calcium-dependent cysteine protease, calpain, have markedly
      different effects on the extent of hypertrophy induced by the alpha-adrenergic
      agonist, phenylephrine, of cultured neonatal rat ventricular myocytes. E64c, an
      inhibitor of calpain and other cysteine proteases, stimulated the hypertrophy by
      59%. PD 150606, a specific calpain inhibitor, reduced the hypertrophy by 38%.
      Phenylephrine decreased the proteolysis of a calpain substrate by the cells 1-2 h
      after its addition but not at 24 h. PD 150606 inhibited proteolytic activity at
      all times, and the combination of phenylephrine and PD 150606 did not give
      greater inhibition. This suggests that cysteine proteases of the papain sub
      family are involved with the hypertrophic response at two points, promoting
      hypertrophy at the first and limiting it at the second. Calpain appears to be the
      protease involved at the first point, and there may be another cysteine protease
      acting at the second site.

PMID- 14575304
TI  - Cardiac adaptation to endurance exercise in rats.
AB  - Endurance exercise is widely assumed to improve cardiac function in humans. This
      project has determined cardiac function following endurance exercise for 6 (n =
      30) or 12 (n = 25) weeks in male Wistar rats (8 weeks old). The exercise protocol
      was 30 min/day at 0.8 km/h for 5 days/week with an endurance test on the 6th day
      by running at 1.2 km/h until exhaustion. Exercise endurance increased by 318%
      after 6 weeks and 609% after 12 weeks. Heart weight/kg body weight increased by
      10.2% after 6 weeks and 24.1% after 12 weeks. Echocardiography after 12 weeks
      showed increases in left ventricular internal diameter in diastole (6.39 +/- 0.32
      to 7.90 +/- 0.17 mm), systolic volume (49 +/- 7 to 83 +/- 11 miccrol) and cardiac
      output (75 +/- 3 to 107 +/- 8 ml/min) but not left wall thickness in diastole
      (1.74 +/- 0.07 to 1.80 +/- 0.06 mm). Isolated Langendorff hearts from trained
      rats displayed decreased left ventricular myocardial stiffness (22 +/- 1.1 to
      19.1 +/- 0.3) and reduced purine efflux during pacing-induced workload increases.
      31P-NMR spectroscopy in isolated hearts from trained rats showed decreased PCr
      and PCr/ATP ratios with increased creatine, AMP and ADP concentrations. Thus,
      this endurance exercise protocol resulted in physiological hypertrophy while
      maintaining or improving cardiac function.

PMID- 14575305
TI  - Matrix metalloproteinase inhibitors attenuate endotoxemia induced cardiac
      dysfunction: a potential role for MMP-9.
AB  - Enhanced cardiac generation of peroxynitrite contributes to septic
      cardiomyopathy. Since matrix metalloproteinases (MMPs) are activated in vitro by
      peroxynitrite, we hypothezised that MMPs may contribute to cardiac mechanical
      dysfunction in sepsis. Rats were injected (i.p.) with either lipopolysaccharide
      (LPS, 4 mg/kg) or vehicle. MMP inhibitors, either Ro 31-9790 (20 mg/kg),
      doxycycline (4 mg/kg), or vehicle were administered i.p. 30 min after LPS. At 6
      h, when the symptoms of endotoxemia peak, hearts were excised and perfused as
      working hearts with Krebs-Henseleit buffer at 37 degrees C. Cardiac work (cardiac
      output x peak systolic pressure product) was measured. Perfusate and ventricle
      samples were analyzed by gelatin zymography to quantify MMP activity. Cardiac
      function was significantly depressed in LPS-treated rats compared to control rats
      (control: 55 +/- 4, LPS: 26 +/- 6 mmHg*mL*min(-1)). LPS also caused a loss of 72
      kDa MMP-2 activity in the ventricles and the perfusate. Although MMP-9 activity
      was not detected in the ventricles, LPS resulted in an increase in perfusate 92
      kDa MMP-9 activity. The MMP inhibitors significantly improved cardiac function of
      LPS-treated rats (Ro 31-9790: 38 +/- 3, doxycycline: 51 +/- 3 mmHg*mL*min(-1)),
      had no effect on the loss of MMP-2 activity, and significantly reduced the MMP-9
      activity in the perfusate. These results demonstrate, for the first time, that
      LPS induced cardiac dysfunction is associated with a loss in ventricular MMP-2
      activity and the release of MMP-9 from the heart. MMP inhibitors can
      significantly preserve cardiac mechanical function during septic shock.

PMID- 14575306
TI  - Functional and structural characterization of anti-beta1-adrenoceptor
      autoantibodies of spontaneously hypertensive rats.
AB  - Eighteen month old spontaneously hypertensive rats (SHR-rats) showed myocardial
      dysfunction and autoantibodies directed against the beta1-adrenoceptor similarly
      as known in human dilated cardiomyopathy or Chagas' disease. The agonist-like
      antibodies were able to activate the beta1-adrenoceptor mediated signal
      transduction cascade in cultured rat cardiomyocytes and induced a long-lasting
      stimulatory effect resulting in a harmful adrenergic overdrive. The antibodies
      recognized an epitope of the second extracellular loop of the beta1-adrenoceptor
      identical to that epitope identified in Chagas' disease. In conclusion, our
      assumption is supported that old SHR-rat are an useful animal model for
      investigating the role of anti-beta1-adrenoceptor antibodies in the induction of
      human cardiomyopathy.

PMID- 14575307
TI  - Quinapril inhibits progression of heart failure and fibrosis in rats with dilated
      cardiomyopathy after myocarditis.
AB  - The cardioprotective properties of quinapril, an angiotensin-converting enzyme
      inhibitor, were studied in a rat model of dilated cardiomyopathy. Twenty-eight
      days after immunization of pig cardiac myosin, four groups rats were given 0.2
      mg/kg (Q0.2, n = 11), 2 mg/kg (Q2, n = 11) or 20 mg/kg (Q20, n = 11) of quinapril
      or vehicle (V, n = 15) orally once a day. After 1 month, left ventricular end
      diastolic pressure (LVEDP), +/- dP/dt, area of myocardial fibrosis, and
      myocardial mRNA expression of transforming growth factor (TGF)-beta1, collagen
      III and fibronectin were measured. Four of 15 (27%) rats in V and two of 11 (18%)
      in Q0.2 died. None of the animals in Q2 or Q20 died. The LVEDP was higher and +/-
      dP/dt was lower in V (14.1 +/- 2.0 mmHg and +2409 +/- 150/-2318 +/- 235 mmHg/sec)
      than in age-matched normal rats (5.0 +/- 0.6 mmHg and +6173 +/- 191/-7120 +/- 74
      mmHg/ sec; all p < 0.01). After quinapril treatment, LVEDP was decreased and +/-
      dP/dt was increased in a dose-dependent manner (10.8 +/- 1.8 mmHg and +3211 +/-
      307/-2928 +/- 390 mmHg/sec in Q0.2, 9.4 +/- 1.5 mmHg and +2871 +/- 270/-2966 +/-
      366 mmHg/sec in Q2, and 6.6 +/- 1.5 mmHg, and +3569 +/- 169/-3960 +/- 203
      mmHg/sec in Q20). Increased expression levels of TGF-beta1, collagen-III and
      fibronectin mRNA in V were reduced in Q20. Quinapril improved survival rate and
      cardiac function in rats with dilated cardiomyopathy after myocarditis.
      Furthermore, myocardial fibrosis was regressed and myocardial structure returned
      to nearly normal in animals treated with quinapril.

PMID- 14575308
TI  - Calpain-1-dependent degradation of troponin I mutants found in familial
      hypertrophic cardiomyopathy.
AB  - The mechanism by which mutations of the cardiac troponin I (cTnI) gene evoke
      familial hypertrophic cardiomyopathy (fHCM) is unknown. In this investigation the
      potential effects of three fHCM-related cTnI mutations on Calpain-1-induced cTnI
      degradation were tested, and a study was made of whether additional
      conformational changes due to troponin complex formation and protein kinase A
      induced phosphorylation affect the intensity of cTnI proteolysis. Purified
      recombinant wild-type cTnI and three of its fHCM-related missense mutants (R145G,
      G203S and K206Q), alone or in the troponin complex (i.e. together with troponin C
      and troponin T), in the non-phosphorylated or protein kinase A-bisphosphorylated
      forms were proteolyzed in vitro in the presence of Calpain-1 (0.05-2.5 U) at 30
      degrees C. Following incubation with Calpain-1 for 0.5, 30, 60 or 120 min, the
      extent of protein degradation was evaluated through the use of Western
      immunoblotting and densitometry. The results indicated that both the wild-type
      and the mutant cTnI molecules were susceptible to Calpain-1. However, the
      degradation of the cTnI molecules in the troponin complex was less intense than
      that of the non-complexed forms. Moreover, phosphorylation by protein kinase A
      conferred effective protection against cTnI proteolysis. The data suggested that
      mutations in the central inhibitory domain (R145G) and in the C-terminal region
      (G203S and K206Q) of cTnI do not affect its Calpain-1-mediated degradation, or
      the phosphorylation-induced protection against proteolysis.

PMID- 14575309
TI  - Gender mediated cardiac protection from adverse ventricular remodeling is
      abolished by ovariectomy.
AB  - Gender differences in the prevalence of cardiovascular disease have been observed
      both clinically and experimentally. These cardioprotective effects have
      frequently been attributed to female hormones, however, the underlying mechanisms
      responsible for this cardioprotection are still poorly understood. Accordingly,
      this study sought to determine the contribution of ovarian hormones to the
      prevention of adverse ventricular remodeling and congestive heart failure in
      chronic volume overload (i.e. aortocaval fistula in intact or ovariectomized
      female rats). Ovariectomized rats developed more extensive cardiac remodeling
      than intact females at 21 weeks post-fistula, characterized by significantly
      greater left ventricular (LV) hypertrophy (167 vs. 86%, respectively, p < 0.05)
      and a substantial increase in LV dilatation (71%, p < 0.05) relative to control.
      In contrast to the eccentric hypertrophy in ovariectomized females post-fistula,
      the hypertrophic response in the intact female hearts was essentially concentric.
      While neither fistula group suffered significant mortality, there was a marked
      increase in the lung weight of ovariectomized rats (87%, p < 0.05) consistent
      with the development of pulmonary edema. Overall, the extent of myocardial
      remodeling and decrease in LV function in the ovariectomized females was
      comparable to those changes reported for males with symptomatic heart failure,
      while intact females maintained chronic compensated ventricular function similar
      to that of controls. The marked ventricular dilatation and symptoms of congestive
      heart failure seen at 21 weeks post-fistula in the ovariectomized females clearly
      demonstrate the influence of circulating ovarian hormones on the pattern of
      myocardial remodeling resulting from a chronic volume overload.

PMID- 14575310
TI  - Protein kinase C isoform-selective signals that lead to cardiac hypertrophy and
      the progression of heart failure.
AB  - Protein kinase C isoforms comprise a family of structurally related
      serine/threonine kinases that are activated by second messenger molecules formed
      via receptor-dependent activation of phospholipase C. Cardiomyocytes co-express
      multiple protein kinase C isoforms which play key roles in a spectrum of adaptive
      and maladaptive cardiac responses. This chapter focuses on the structural
      features, modes of activation, and distinct cellular actions of individual PKC
      isoforms in the heart. Particular emphasis is placed on progress that comes from
      studies in molecular models of PKC isoform overexpression or gene deletion in
      mice. Recent studies that distinguish the functional properties of novel PKC
      isoforms (PKC(delta) and PKC(epsilon)) from each other, and from the actions of
      the conventional PKC isoforms, and suggest that these proteins may play a
      particularly significant role in pathways leading to cardiac growth and/or
      cardioprotection also are considered.

PMID- 14575311
TI  - Contractile effects of adenovirally-mediated increases in SERCA2a activity: a
      comparison between adult rat and rabbit ventricular myocytes.
AB  - Adenoviral vectors have been successfully used to increase the activity of the
      sarcoplasmic reticulum Ca(2+)-ATPase in adult ventricular myocytes and to produce
      functional improvements in contractility in vivo and in vitro. While in vivo
      experiments are often performed in rat, in vitro manipulation of myocytes has
      been confined to rabbit and human cells. In the present study we make
      quantitative comparisons between cultured adult rat and rabbit myocytes in their
      responses to SERCA2a overexpression using adenoviral vectors. We also compare the
      strategy of SERCA2a overexpression with that of phospholamban down-regulation,
      using adenovirus carrying antisense message, as a means to increase SERCA2a
      activity and enhance contraction and relaxation. Adult myocytes were cultured for
      48 h with either vector, and contraction assessed in 2 mM Ca2+, 37 degrees C, at
      a range of stimulation frequencies. Contraction amplitude was enhanced to a
      similar degree in either rat or rabbit myocytes at most stimulation frequencies,
      with SERCA2a overexpression and phospholamban down-regulation approximately
      equally effective. The maximum effect of either vector was less than that of beta
      adrenoceptor agonists. Relaxation was accelerated in rabbit myocytes more
      strongly than in rat. Phospholamban antisense was slightly less effective than
      SERCA2a overexpression on relaxation times in rabbit. Increasing stimulation
      frequency also accelerated relaxation in rat myocytes: this effect was greater
      than, and additive with, that of SERCA2a overexpression. We conclude that,
      despite some species-dependent modification, the effects of increased SERCA2a
      activity are broadly similar in rat and rabbit. Both SERCA2a overexpression and
      phospholamban down-regulation are effective strategies, and neither appears to
      produce supraphysiological stimulatory effects on contraction or relaxation.

PMID- 14575312
TI  - Losartan inhibits myosin isoform shift after myocardial infarction in rats.
AB  - Hypertrophy and heart failure following a myocardial infarction in rodents are
      accompanied by a switch of myosin isoforms from V1 to V3. The angiotensin II
      receptor blocker, Losartan, has been demonstrated to improve cardiac function and
      long-term survival after myocardial infarction. In this study we have
      investigated whether chronic Losartan treatment affects myosin isoform
      composition in the hearts of rats following a myocardial infarction. Rats were
      subjected to coronary artery ligation and received either Losartan (1 g/L) in the
      drinking water or water only. Four months after myocardial infarction, rats were
      classified as having either congestive heart failure (cMI) or uncomplicated
      myocardial infarction (uMI) based on their lung weight to body weight ratio
      (LW/BW). Compared with sham operated rats, uMI rats showed a 68.5% increase in
      the relative contribution of V3 and a 33.7% decrease in the relative contribution
      of V1 (p < 0.05). Untreated cMI showed 39.7% more V3 and 38.2% less V1 when
      compared with untreated uMI (p < 0.05). Losartan treatment after myocardial
      infarction reduced the incidence of cMI from 30.4 to 4.5% and scar size from 1.52
      +/- 0.07 to 0.94 +/- 0.11 cm2 respectively. The percentage of V1 in Losartan
      treated uMI (LuMI) was 25.2% higher than the percentage of V1 in untreated uMI (p
      < 0.05), whereas the percentage of V3 in LuMI was 24.2% lower than that in
      untreated uMI (p < 0.05). A positive correlation of V3 myosin and scar area was
      observed. Our study suggests that expression of V3 myosin in the left ventricle
      is associated with scar size and the progress of hemodynamic changes after
      myocardial infarction. Losartan treatment reduces scar size and wall stress of
      the heart after the infarct, and therefore inhibits the signals shifting myosin
      isoform expression from V1 to V3 after a myocardial infarction.

PMID- 14575313
TI  - Mechanism of cell death of rat cardiac fibroblasts induced by serum depletion.
AB  - Serum starvation has recently been shown to cause cell death of cardiac
      fibroblasts and increased synthesis of extracellular matrix proteins in the
      surviving cells. In the present study, events occurring in the dying cells were
      investigated. Cultured adult rat cardiac fibroblasts were exposed to serum-free
      medium. Cell number was measured using a Coulter Counter Channelyzer. The
      activity of the extracellular signal-regulated or mitogen-activated protein
      kinases (ERK1/2, p42/p44(MAPK)), the p38 kinase (p38(MAPK)), the c-Jun N-terminal
      kinases (p46/p54(JNK)), and Akt kinase was assessed by Western blotting and
      phospho-specific antibodies. Caspase 7-cleavage was investigated by Western
      blotting and specific antibodies. Caspase 3 activity was measured by detection of
      its cleaved substrate. The appearance of necrosis was studied by inclusion of
      trypan blue. Apoptosis was assessed by DNA ladder formation. The mRNA expression
      of Bax and Bcl-2 was investigated by quantitative real-time PCR. Serum withdrawal
      led to the death of 26% of cultured isolated cardiac fibroblasts during the first
      5 h. The activity of the p42/ p44(MAPK) as well as of Akt kinase was partially
      reduced. For p46/p54(JNK) and p38(MAPK), elevated phosphorylation was measured.
      Inhibition of p46/p54(JNK) and p38(MAPK) activity by SB202190 did not affect the
      decrease in cell number. Cleavage of caspase 7 was detected after 90 min.
      However, no activation of caspase 3 was measured. DNA fragmentation was not found
      after serum depletion. Trypan blue staining, however, was observed in 16% of the
      cells after 5 h. The mRNA levels of both Bax and Bcl-2 were increased after 30
      min. These results indicate the appearance of necrosis during serum starvation in
      cardiac fibroblasts. However, some processes typical of apoptosis were also
      detected.

PMID- 14575315
TI  - Revisiting the surgical creation of volume load by aorto-caval shunt in rats.
AB  - Cardiac hypertrophy is an early landmark during the clinical course of heart
      failure, and is an important risk factor for subsequent morbidity and mortality.
      The hypertrophy response to different types of cardiac overload is distinguished
      both at the molecular and cellular levels. These changes have been extensively
      characterized for pressure load hypertrophy; however, similar information for
      volume load hypertrophy is still needed. This study was undertaken to improve the
      existing method of producing experimental cardiac volume load. Previous
      investigators have employed surgical aorto-caval shunt (ACS) as a model for
      volume load hypertrophy (VO) in rats. The procedure is relatively simple and
      involves glue to seal the aortic hole after ACS. However, it has several
      limitations mostly related to the use of glue e.g. poor visualization due to
      hardening of tissues, imperfect sealing of the puncture site and glue seeping
      through the aortic hole resulting in shunt occlusion. We have modified the
      procedure using aortic adventitial suture instead of glue and 18G angiocatheter
      instead of 16G needle, which eliminated the technical difficulties from the
      former method. The ACS was visually confirmed at sacrifice, and the VO
      demonstrated by time-related changes in the heart weight/body weight ratio which
      increased from 78% at 4 weeks to 87% at 10 weeks and increased liver/body weight
      ratio by 22% at 10 weeks of post aorto-caval shunt. Cardiac expression of atrial
      natriuretic peptide (ANF) also demonstrated time-related increase in ANF mRNA
      (+275% increase at 4 weeks, p < 0.05, and +370% increase at 10 weeks, p < 0.001).
      This modified technique of aorto-caval shunt offers simpler, reproducible and
      consistent model for VO hypertrophy in rats.

PMID- 14575314
TI  - Effect of propranolol on cardiac cytokine expression after myocardial infarction
      in rats.
AB  - The pro-inflammatory cytokines interleukin (IL)-1beta and IL-6 have been shown to
      be upregulated in the myocardium after injury and after adrenergic receptor
      stimulation. Together with other cytokines, such as the transforming growth
      factor (TGF)-beta, the pro-inflammatory cytokines have been implicated in the
      initiation of tissue repair and wound healing after myocardial infarction (MI).
      In the present study, the effect of beta-adrenergic receptor blockade with
      propranolol (2 mg/kg x h s.c. by miniosmotic pumps) on cardiac cytokine
      expression and on wound healing was analyzed in rats from 6-72 h after MI. IL
      1beta and IL-6 gene expression strongly increased in the infarcted myocardium 6 h
      after MI and peaked after 12 h, while TGF-beta, progressively increased from 12 h
      onwards. Also, TGF-beta2 increased after 12 h, peaked after 24 h and declined
      thereafter, while TGF-beta, was only elevated after 72 h. Treatment with
      propranolol had a negative chronotropic effect throughout the observation period
      of 72 h. It attenuated the initial elevation in LVEDP and increased cardiac
      output ultimately. Furthermore, propranolol attenuated IL-1beta mRNA expression,
      but had not effect on the other cytokines. Moreover, MMP-9 gelatinolytic activity
      was markedly attenuated by propranolol indicating a delayed resorption of the
      necrotic tissue and, possibly, collagen turnover. Replacement by scar tissue,
      however, was not affected as indicated by normal collagen expression.

PMID- 14575316
TI  - Proteomic analysis of Rac1 transgenic mice displaying dilated cardiomyopathy
      reveals an increase in creatine kinase M-chain protein abundance.
AB  - Here, we demonstrate the application of the proteomic approach to the study of a
      transgenic mouse model of heart failure and provide an example of a disease
      associated protein alteration that can be observed using this approach.
      Specifically, we applied the proteomic approach to the analysis of a mouse model
      of dilated cardiomyopathy in which the small GTPase, Rac1, was constitutively
      expressed specifically in the myocardium. We utilized the methods of two
      dimensional gel electrophoresis (2-DE) for protein separation, silver-staining
      for protein visualization and mass spectrometry (MALDI-TOF and MS/MS) for protein
      spot identification. Computer-generated composite images were created which
      represent a normalized average of four 2-DE gel images derived from analysis of
      either Rac1 transgenic (n = 4) or non-transgenic (n = 4) mice. Analysis of
      composite images derived from NTG and Rac1 experimental groups revealed numerous
      statistically significant differences in mean protein spot intensities. Here, we
      report a statistically significant increase, of approximately 1.6-fold, in the
      mean protein spot intensity for creatine kinase M-chain in the composite image of
      Rac1 transgenic mice compared to control. This protein alteration may be
      consistent with an end-stage heart failure phenotype in which maximal myocardial
      reserve is employed to sustain survival.

PMID- 14575317
TI  - Adenosine and cardioprotection during reperfusion--an overview.
AB  - Ischemic heart disease includes a number of entities that have been grouped in
      accordance with physiopathology and evolutive criteria. In recent years 'new'
      ischemic syndromes have been described. Within the 'new' ischemic syndromes,
      ventricular post-ischemic dysfunction--also known as 'stunned myocardium'--is
      worth mentioning. In this route, several studies have suggested that reperfusion
      per se could cause cellular injury (reperfusion injury). In previous years, a
      protective effect on the injury caused by ischemia and reperfusion in the heart
      has been attributed to adenosine. These effects have been documented in different
      experimental in vivo and in vitro models. Thus, the administration of exogenous
      adenosine, or agonists of adenosine receptors prior to ischemia reduces the size
      of the infarction, improves the recovery of the ventricular function during
      reperfusion (attenuating stunning) and prolongs the time period to the ischemic
      contracture. However, focusing on a potential therapeutic application, it is of
      the utmost importance to find this protection and learn the mechanisms involved
      when procedures are applied during early reperfusion. We showed that adenosine,
      administered from the beginning of reperfusion, attenuated systolic and diastolic
      (myocardial stiffness) alterations of the stunned myocardium. This protective
      effect was mediated by the activation of A1 adenosine receptors, and without
      modification on infarct size. According to some authors, adenosine can decrease
      the release of endothelin, during early reperfusion, and reduce an overload of
      Ca2+ that could cause a cellular lesion. Finally, ischemic preconditioning
      involves a series of intracellular events that are initiated with the activation
      of the A1 receptor, and end at the sensitive K+ ATP channels of the mitochondria.
      The phosphorylation and opening of these channels would cause the protective
      effect. Activation of this specific mechanism during reperfusion has not been
      studied extensively.

PMID- 14575318
TI  - Retraction.

PMID- 14575319
TI  - Perspective: Evolution and detection of genetic robustness.
AB  - Robustness is the invariance of phenotypes in the face of perturbation. The
      robustness of phenotypes appears at various levels of biological organization,
      including gene expression, protein folding, metabolic flux, physiological
      homeostasis, development, and even organismal fitness. The mechanisms underlying
      robustness are diverse, ranging from thermodynamic stability at the RNA and
      protein level to behavior at the organismal level. Phenotypes can be robust
      either against heritable perturbations (e.g., mutations) or nonheritable
      perturbations (e.g., the weather). Here we primarily focus on the first kind of
      robustness--genetic robustness--and survey three growing avenues of research: (1)
      measuring genetic robustness in nature and in the laboratory; (2) understanding
      the evolution of genetic robustness: and (3) exploring the implications of
      genetic robustness for future evolution.

PMID- 14575320
TI  - Life-history differentiation and the maintenance of monoecy and dioecy in
      Sagittaria latifolia (Alismataceae).
AB  - The existence of monoecious and dioecious populations within plant species is
      rare. This limits opportunities to investigate the ecological mechanisms
      responsible for the evolution and maintenance of these contrasting sexual
      systems. In Sagittaria latifolia, an aquatic flowering plant, monoecious and
      dioecious populations exist in close geographic proximity but occupy distinct
      wetland habitats differing in the relative importance of disturbance and
      competition, respectively. Life-history theory predicts contrasting evolutionary
      responses to these environmental conditions. We propose that the maintenance of
      monoecy and dioecy in S. latifolia is governed by ecological selection of
      divergent life-history strategies in contrasting habitats. Here we evaluate this
      hypothesis by comparing components of growth and reproduction between monoecious
      and dioecious populations under four conditions: natural populations, a uniform
      glasshouse environment, a common garden in which monoecious and dioecious
      populations and their F1 progeny were compared, and a transplant experiment using
      shaded and unshaded plots in a freshwater marsh. Plants from dioecious
      populations were larger in size and produced heavier corms in comparison with
      monoecious populations. Monoecious populations flowered earlier and produced more
      flowers, clonal ramets, and corms than dioecious populations. The life-history
      differences between the sexual systems were shown to have a quantitative genetic
      basis, with F1 progeny generally exhibiting intermediate trait values. Survival
      was highest for each sexual system in field plots that most closely resembled the
      habitats in which monoecious (unshaded) and dioecious (shaded) populations grow.
      These results demonstrate that monoecious and dioecious populations exhibit
      contrasting patterns of investment in traits involved with growth and
      reproduction. Selection for divergent life histories between monoecious and
      dioecious populations of S. latifolia appears to be the principal mechanism
      maintaining the integrity of the two sexual systems in areas of geographic
      overlap.

PMID- 14575321
TI  - The origin of ecological divergence in Helianthus paradoxus (Asteraceae):
      selection on transgressive characters in a novel hybrid habitat.
AB  - Diploid hybrid speciation in plants is often accompanied by rapid ecological
      divergence between incipient neospecies and their parental taxa. One plausible
      means by which novel adaptation in hybrid lineages may arise is transgressive
      segregation, that is, the generation of extreme phenotypes that exceed those of
      the parental lines. Early generation (BC2) hybrids between two wild, annual
      sunflowers, Helianthus annuus and Helianthus petiolaris, were used to study
      directional selection on transgressive characters associated with the origin of
      Helianthus paradoxus, a diploid hybrid species adapted to extremely saline
      marshes. The BC2 plants descended from a single F1 hybrid backcrossed toward H.
      petiolaris. The strength of selection on candidate adaptive traits in the
      interspecific BC2 was measured in natural H. paradoxus salt marsh habitat.
      Positive directional selection was detected for leaf succulence and Ca uptake,
      two traits that are known to be important in salt stress response in plants.
      Strong negative directional selection operated on uptake of Na and correlated
      elements. A significant decrease in trait correlations over time was observed in
      the BC2 population for Na and Ca content, suggesting an adaptive role for
      increased Ca uptake coupled with increased net exclusion of Na from leaves.
      Patterns of directional selection in BC2 hybrids were concordant with character
      expression in the natural hybrid species, H. paradoxus, transplanted into the
      wild. Moreover, the necessary variation for generating the H. paradoxus phenotype
      existed only in the BC2 population, but not in samples of the two parental
      species, H. annuus and H. petiolaris. These results are consistent with the
      hypothesis that transgressive segregation of elemental uptake and leaf succulence
      contributed to the origin of salt adaptation in the diploid hybrid species H.
      paradoxus.

PMID- 14575322
TI  - Contrasting flowering phenology and species richness in abiotically and
      biotically pollinated angiosperms.
AB  - Biotic pollination is thought to correlate with increased interspecific
      competition for pollination among plants and a higher speciation rate. In this
      study we compared patterns of flowering phenology and species richness between
      abiotically (wind) and biotically pollinated plants, using phylogenetically
      independent contrasts. We compiled phenological data from eight local seasonal
      floras, in which we found geographically overlapping sister clades. Of 65
      documented origins of wind pollination, we were able to use up to 17 independent
      contrasts. In contrast to previous studies we found no difference in global
      species richness between wind- and biotically pollinated sister clades. Regarding
      phenology, we found wider phenological spread in biotically pollinated clades,
      earlier flowering onset in wind-pollinated trees, but no difference in duration
      of flowering between pollination modes. These results corroborate previous views
      that niche space is more constrained for wind-pollinated species, and that niche
      partitioning is less important between wind-pollinated plants compared to plants
      pollinated by animals.

PMID- 14575323
TI  - Constraints on the evolution of males and sexual dimorphism: field estimates of
      genetic architecture of reproductive traits in three populations of gynodioecious
      Fragaria virginiana.
AB  - To understand how genetic constraints may limit the evolution of males and sexual
      dimorphism in a gynodioecious species, I conducted a quantitative genetic
      experiment in a gynodioecious wild strawberry, Fragaria virginiana. I estimated
      and compared genetic parameters (narrow-sense heritabilities, between-trait and
      between-sex genetic correlations, as well as phenotypic and genetic variance
      covariance matrices) in the two sex morphs from three populations grown in a
      common field garden. I measured pollen and ovule production per flower, petal
      size, fruit set, and flower number. My major findings are as follows. (1) The
      presence of a phenotypic trade-off between pollen production and fruit set in
      hermaphrodites reflects a negative genetic correlation in the narrow sense that
      is statistically significant when pooled across populations. (2) The main
      constraints on the evolution of males are low genetic variation for pollen per
      flower and strong positive correlations associated with ovule number (e.g.,
      between pollen and ovules in hermaphrodites, and between ovules in hermaphrodites
      and females). (3) Traits with the lowest levels of sexual dimorphism (ovule
      number and flower number) have the highest between-sex genetic correlations
      suggesting that overlap in the expression of genes in the sex morphs constrains
      their independent evolution. (4) There are significant differences in G matrices
      between sex morphs but not among populations. However, evidence that male-female
      trait correlations in hermaphrodites were lower in populations with higher
      frequencies of females may indicate subtle changes in genetic architecture.

PMID- 14575324
TI  - Phylogeography of the pantropical sea urchin Tripneustes: contrasting patterns of
      population structure between oceans.
AB  - To understand how allopatric speciation proceeds, we need information on barriers
      to gene flow, their antiquity, and their efficacy. For marine organisms with
      planktonic larvae, much of this information can only be obtained through the
      determination of divergence between populations. We evaluated the importance of
      ocean barriers by studying the mitochondrial DNA phylogeography of Tripneustes, a
      pantropical genus of shallow water sea urchin. A region of cytochrome oxidase I
      (COI) was sequenced in 187 individuals from locations around the globe. The COI
      phylogeny agreed with a previously published phylogeny of bindin that barriers
      important to the evolution of Tripneustes are: (1) the cold water upwelling close
      to the tip of South Africa, (2) the Isthmus of Panama, (3) the long stretch of
      deep water separating the eastern from the western Atlantic, and (4) the
      freshwater plume of the Orinoco and the Amazon rivers between the Caribbean and
      the coast of Brazil. These barriers have previously been shown to be important in
      at least a subset of the shallow water marine organisms in which phylogeography
      has been studied. In contrast, the Eastern Pacific Barrier, 5000 km of deep water
      between the central and the eastern Pacific that has caused the deepest splits in
      other genera of sea urchins, is remarkably unimportant as a cause of genetic
      subdivision in Tripneustes. There is also no discernible subdivision between the
      Pacific and Indian Ocean populations of this genus. The most common COI haplotype
      is found in the eastern, central, and western Pacific as well as the Indian
      Ocean. Morphology, COI, and bindin data agree that T. depressus from the eastern
      Pacific and T. gratilla from the western Pacific are, in fact, the same species.
      The distribution of haplotype differences in the Indo-Pacific exhibits
      characteristics expected from a sea urchin genus with ephemeral local
      populations, but with high fecundity, dispersal, and growth: there is little
      phylogenetic structure, and mismatch distributions conform to models of recent
      population expansion on a nearly global scale. Yet, comparisons between local
      populations produce large and significant F(ST) values, indicating nonrandom
      haplotype distribution. This apparent local differentiation is only weakly
      reflected in regional divergence, and there is no evidence of isolation by
      distance in correlations between F(ST) values and either geographical or current
      distance. Thus, Tripneustes in the Indo-Pacific (but not in the Atlantic) seems
      to be one large metapopulation spanning two oceans and containing chaotic,
      nonequilibrium local variation, produced by the haphazard arrival of larvae or by
      unpredictable local extinction.

PMID- 14575325
TI  - Indiscriminate females and choosy males: within- and between-species variation in
      Drosophila.
AB  - The classic view of choosy, passive females and indiscriminate, competitive males
      gained theoretical foundations with parental investment theory. When females
      invest more in offspring than males, parental investment theory says that
      selection operates so that females discriminate among males for mates (i.e.,
      females are choosy and passive) and males are indiscriminate (i.e., males are
      profligate and competitive). Here we report tests of predictions using Drosophila
      pseudoobscura and D. melanogaster, with typical asymmetry in gamete sizes
      (females > males), and in D. hydei with far less asymmetry in gamete size.
      Experimental observations revealed that the labels "choosy, passive females" and
      "profligate, indiscriminate males" did not capture the variation within and
      between species in premating behavior. In each of the species some females were
      as active in approaching males (or more so) than males in approaching females,
      and some males were as discriminating (or more so) than females. In pairs focal
      males and females responded differently to opposite-sex than to same-sex
      conspecifics. Drosophila hydei were less sex-role stereotyped than the other two
      species consistent with parental investment theory. However, D. pseudoobscura
      females approached males more often than did D. melanogaster females, and male D.
      hydei approached females as often as males of the other two species, both results
      inconsistent with parental investment theory. Male D. pseudoobscura and D. hydei
      were more likely to approach males in same-sex pairs than male D. melanogaster,
      inconsistent with parental investment theory.

PMID- 14575326
TI  - Interactions among mechanisms of sexual selection on male body size and head
      shape in a sexually dimorphic fly.
AB  - Darwin envisaged male-male and male-female interactions as mutually supporting
      mechanisms of sexual selection, in which the best armed males were also the most
      attractive to females. Although this belief continues to predominate today, it
      has been challenged by sexual conflict theory, which suggests that divergence in
      the interests of males and females may result in conflicting sexual selection.
      This raises the empirical question of how multiple mechanisms of sexual selection
      interact to shape targeted traits. We investigated sexual selection on male
      morphology in the sexually dimorphic fly Prochyliza xanthostoma, using indices of
      male performance in male-male and male-female interactions in laboratory arenas
      to calculate gradients of direct, linear selection on male body size and an index
      of head elongation. In male-male combat, the first interaction with a new
      opponent selected for large body size but reduced head elongation, whereas
      multiple interactions with the same opponent favored large body size only. In
      male-female interactions, females preferred males with relatively elongated
      heads, but male performance of the precopulatory leap favored large body size
      and, possibly, reduced head elongation. In addition, the amount of sperm
      transferred (much of which is ingested by females) was an increasing function of
      both body size and head elongation. Thus, whereas both male-male and male-female
      interactions favored large male body size, male head shape appeared to be subject
      to conflicting sexual selection. We argue that conflicting sexual selection may
      be a common result of divergence in the interests of the sexes.

PMID- 14575327
TI  - Female life span and fertility are increased by the ejaculates of preferred
      males.
AB  - In animals with internal fertilization, sperm competition among males can favor
      the evolution of male ejaculate traits that are detrimental to females. Female
      mating preferences, in contrast, often favor traits in males that are beneficial
      to females, yet little is known about the effect of these preferences on the
      evolution of male ejaculates. A necessary condition for female preferences to
      affect the evolution of male ejaculate characteristics is that females select
      mates based on a trait correlated with ejaculate quality. Previous work has shown
      that females of the variable field cricket, Gryllus lineaticeps, prefer males
      that produce calling songs containing faster and longer chirps. In this study, we
      tested the hypothesis that females receive more beneficial ejaculates from
      preferred males. Females were placed on either a high- or a reduced-nutrition
      diet then mated twice to a male of known song phenotype. Females received only
      sperm and seminal fluid from males during these matings. There was no effect of
      male song phenotype on any fitness component for females on the high-nutrition
      diet. Reduced-nutrition females mated to males that produced preferred song
      types, however, lived longer, produced more eggs, produced more fertile eggs, and
      had a higher proportion of their eggs fertilized than those mated to other males.
      The life-span benefit was positively associated with male chirp duration, and the
      reproductive benefits were positively associated with male chirp rate. We
      explored two possible mechanisms for the life span and reproductive benefits.
      First, a path analysis suggested that part of the effect of male chirp duration
      on female life span may have been indirect; females mated to males that produced
      longer chirps showed delayed oviposition, and females that delayed oviposition
      lived longer. Males that produce longer chirps may thus transfer fewer or less
      potent oviposition stimulants to females in their seminal fluid. Second, there
      was a positive correlation between male chirp rate and the number of sperm
      transferred to females. The fertility benefit may thus have resulted from females
      receiving more sperm from males that produce faster chirps. Finally, there was a
      negative phenotypic correlation between male chirp rate and chirp duration,
      suggesting that females may have to trade off the life span and reproduction
      benefits when selecting a mate.

PMID- 14575328
TI  - The evolution of female multiple mating in social hymenoptera.
AB  - The evolution of female multiple mating is a highly controversial topic,
      especially in social insects. Here we analyze, using comparative analyses and
      simulation models, the merits of two major contending hypotheses for the adaptive
      value of polyandry in this group. The hypotheses maintain that, respectively, the
      resulting genotypic diversity among offspring within a colony: (1) mitigates
      against the effects of parasites; or (2) favors adaptive division of labor. Only
      two of 11 phylogenetically uncontrolled comparative analyses supported an
      association between polyandry and the complexity of division of labor (measured
      here using worker caste polymorphism or polyethism) as proposed by hypothesis 2,
      and after controlling for phylogeny there were no significant associations. In
      contrast, a previous study demonstrated such an association for parasite load as
      expected under hypothesis 1. In addition, we used simulation models to track the
      spread of an initially rare allele for double mating in a population of single
      mating alleles, thus analyzing the crucial first step from monandry to polyandry.
      We find that double mating evolves consistently under antagonistic coevolution
      given that parasites exert sufficient selection intensity. In contrast, selection
      for enhanced division of labor resulted in only an erratic appearance of
      polyandry in highly (and mostly negatively) autocorrelated environments where no
      coevolutionary dynamics were allowed. Together, we interpret these results to
      suggest that parasites, and the antagonistic coevolutionary pressures they exert,
      may play an important role in the evolution of polyandry in social hymenopteran
      populations.

PMID- 14575329
TI  - Comparative tests of evolutionary trade-offs in a palinurid lobster acoustic
      system.
AB  - Communication structures vary greatly in size and can be structurally and
      behaviorally integrated with other systems. In structurally integrated systems,
      dramatic changes in size may impose trade-offs with the size of neighboring
      structures. In spiny lobsters (Palinuridae), there is a fivefold difference in
      size of the antennular plate, on which sound producing apparatus is located, such
      that the antennular plate reaches 38% carapace length in some sound producers
      (Stridentes) compared to only 4% carapace length in non-sound producing spiny
      lobsters (Silentes). We examined whether this major variation in antennular plate
      size imposes trade-offs with the adjoining antennae, specifically in the context
      that the signal producing structures and antennae are both used in predator
      defense. We recorded and analyzed lobster sounds in order to test whether size
      increases in the acoustic morphology were correlated with production of
      particular signal features. Antennal and antennular plate structures were
      measured across the family, including both Stridentes and Silentes. Phylogenetic
      comparative methods were used to test for correlated evolutionary change among
      the structures and signal features. We analyzed the phylogenetic relationships of
      the Palinuridae based on morphological characters and ribosomal DNA evidence
      (16S, 18S and 28S nuclear and mitochondrial ribosomal RNA gene regions). We found
      that the number of sound pulses was positively correlated with length of the
      sound producing apparatus. Opposite to the predicted trade-offs, we found that
      the size of the antennular plate was positively correlated with size of the
      surrounding antennae within Stridentes. Nevertheless, when Stridentes were
      compared to Silentes, the latter had relatively larger antennae for a given
      antennular plate size than did the sound producing taxa. These results suggest
      that body size does not limit size increases in acoustic structures within
      Stridentes, however the presence and associated constructional costs of a sound
      producing apparatus may impose a trade-off when taxa with and without the
      apparatus are compared. Alternatively, since both systems are used in predator
      defense, this pattern may indicate greater selection for antennal force
      production in Silentes, which lack the additional acoustic mode of predator
      defense.

PMID- 14575330
TI  - Linear habitats and the nested clade analysis: an empirical evaluation of
      geographic versus river distances using an Ozark crayfish (Decapoda: Cambaridae).
AB  - The nested clade analysis can be extremely useful in testing for an association
      between genetic variation and geography and in explaining these observed patterns
      in terms of historical or contemporary population processes. The strength of this
      method lies in its ability to test a variety of processes simultaneously under a
      rigorous statistical framework. Indeed, many recent studies have used the nested
      analysis in a wide range of terrestrial and aquatic taxa. However, it has been
      suggested that riverine, riparian, or coastal species may be better examined
      using river (or coastal) distances rather than the standard geographic (great
      circle) distances among populations. It is thought that the standard geographic
      distances may not adequately describe the actual distances involved between
      populations of species inhabiting these one-dimensional (riverine) habitats.
      Therefore, we analyzed population data from an Ozark crayfish, Orconectes
      lutetus, to examine the effects on the results of a nested clade analysis using
      river distances. In most cases, the haplotypes detected in this crayfish were
      unique to a particular drainage or a group of neighboring drainages, indicating
      very little movement of individuals among drainages. Five major population groups
      were detected, corresponding to many of the major river drainages sampled in this
      study. The two types of distance analyses obtain similar results for higher-level
      (older) clades, but differ in many of the inferences made for lower-level
      (younger) clades. However, we suggest that the comparison of both types of
      analyses for riverine species may enhance the process of elucidating historical
      and contemporary population processes, especially in cases where the transfer of
      individuals among different drainages are involved.

PMID- 14575331
TI  - Rapid growth results in increased susceptibility to predation in Menidia menidia.
AB  - Several recent studies have demonstrated that rapid growth early in life leads to
      decreased physiological performance. Nearly all involved experiments over short
      time periods (<1 day) to control for potentially confounding effects of size.
      This approach, however, neglects the benefits an individual accrues by growing.
      The net effect of growth can only be evaluated over a longer interval in which
      rapidly growing individuals are allowed the time required to attain the expected
      benefits of large size. We used two populations of Menidia menidia with disparate
      intrinsic growth rates to address this issue. We compared growth and survivorship
      among populations subject to predation in mesocosms under ambient light and
      temperature conditions for a period of up to 30 days to address two questions: Do
      the growth rates of fish in these populations respond differently to the presence
      of predators? Is the previously demonstrated survival cost of growth
      counterbalanced by the benefits of increased size? We found that growth was
      insensitive to predation risk: neither population appeared to modify growth rates
      in response to predation levels. Moreover, the fast-growing population suffered
      significantly higher mortality throughout the trials despite being 40% larger
      than the slow-growing population at the experiment's end. These results confirm
      that the costs of rapid growth extend over prolonged intervals and are not
      ameliorated merely by the attainment of large size.

PMID- 14575332
TI  - Asymmetry in structural defenses: insights into selective predation in the wild.
AB  - Assessment of geographical patterns in fluctuating asymmetry (small, random
      differences between sides of bilateral characters) among populations shows
      promise as a tool to resolve the relative biomechanical importance of traits, in
      addition to being a possible indicator of habitat quality. We used 115 endemic
      freshwater populations of threespine stickleback (Gasterosteus aculeatus) from
      Haida Gwaii (Queen Charlotte Islands), British Columbia, Canada, to explore the
      degree of concordance between geographical variation of asymmetry in a predator
      defense structure (bony lateral plates) and geographical variation in several
      indirect measures of predation regime as well as several abiotic habitat
      variables. We found a geographical cline in the population frequency of lateral
      plate asymmetries, with reduced asymmetry in the southern clear-water regions of
      the archipelago characterized by long reaction distances and greater chance of
      capture by predators, and elevated asymmetry in the northern stained-water
      regions with poor visibility and low chances of capture. Lateral plate asymmetry
      was strongly correlated with expression of several defensive armor traits,
      including total plate numbers among populations, mean cross-sectional diameter of
      stickleback with the dorsal and pelvic spines erect, and mean degree of overlap
      between the plates and spine supports. There were no significant correlations
      between frequency of asymmetric fish and any of our abiotic habitat variables.
      Stickleback with structural plate asymmetries had fewer trout-induced scars than
      symmetric fish in the significant majority of populations, and there was a
      decrease in structural plate asymmetry with age in stained-water habitats,
      suggesting that trout predators may be selectively removing asymmetric fish in
      some lakes. This study provides evidence that geographical variation in
      developmental stability of threespine stickleback, as seen in the frequencies of
      asymmetry, reflects differences among populations in the importance of structural
      defenses to fitness rather than differences in habitat quality, and that
      asymmetry may be a target of selection by predators in wild populations.

PMID- 14575333
TI  - Mutation and sexual selection: a test using barn swallows from Chernobyl.
AB  - Secondary sexual characters have been hypothesized to be particularly susceptible
      to the deleterious effects of mutation because the expression of such characters
      is usually influenced by many more metabolic pathways than are ordinary
      morphological characters. We tested this hypothesis using the elevated mutation
      rates in the barn swallow (Hirundo rustica) of the Chernobyl region of Ukraine as
      a model system. A great deal is known about the relative importance of different
      characters for male mating success in this species. The importance of phenotypic
      characters for male mating success was quantified based on a long-term study of a
      Danish breeding population, by expressing phenotypic differences between mated
      and unmated males as the difference between log-transformed mean values. For
      field samples from Ukraine we likewise expressed the difference in male phenotype
      between individuals living in a relatively uncontaminated area and individuals
      from the Chernobyl region as the difference between log-transformed mean values.
      The standardized difference in male phenotype between the two regions in Ukraine
      for the 41 different characters was strongly positively correlated with the
      standardized difference in male phenotype between mated and unmated males from
      Denmark. The standardized difference in male phenotype between the two regions in
      Ukraine was significantly positively associated with sexual size dimorphism.
      However, the standardized difference in male phenotype between mated and unmated
      males was a much better predictor of standardized difference in male phenotype
      between the two regions in Ukraine than was the standardized difference in sexual
      size dimorphism, expressed as the difference between log-transformed mean values
      for males and females. These findings are consistent with the hypothesis that
      traits most important for sexual selection are particularly susceptible to the
      effects of deleterious mutations.

PMID- 14575334
TI  - Morphological shifts in island-dwelling birds: the roles of generalist foraging
      and niche expansion.
AB  - Passerine birds living on islands are usually larger than their mainland
      counterparts, in terms of both body size and bill size. One explanation for this
      island rule is that shifts in morphology are an adaptation to facilitate
      ecological niche expansion. In insular passerines, for instance, increased bill
      size may facilitate generalist foraging because it allows access to a broader
      range of feeding niches. Here we use morphologically and ecologically divergent
      races of white-eyes (Zosteropidae) to test three predictions of this explanation:
      (1) island populations show a wider feeding niche than mainland populations; (2)
      island-dwelling populations are made up of individual generalists; and (3) within
      insular populations there is a positive association between size and degree of
      foraging generalism. Our results provide only partial support for the traditional
      explanation. In agreement with the core prediction, island populations of white
      eye do consistently display a wider feeding niche than comparative mainland
      populations. However, observations of individually marked birds reveal that
      island-dwelling individuals are actually more specialized than expected by
      chance. Additionally, neither large body size nor large bill size are associated
      with generalist foraging behavior per se. These latter results remained
      consistent whether we base our tests on natural foraging behavior or on
      observations at an experimental tree, and whether we use data from single or
      multiple cohorts. Taken together, our results suggest that generalist foraging
      and niche expansion are not the full explanation for morphological shifts in
      island-dwelling white-eyes. Hence, we review briefly five alternative
      explanations for morphological divergence in insular populations: environmental
      determination of morphology, reduced predation pressure, physiological
      optimization, limited dispersal, and intraspecific dominance.

PMID- 14575335
TI  - Genetic benefits of mate choice separated from differential maternal investment
      in red junglefowl (Gallus gallus).
AB  - Females may choose more attractive mates to obtain better viability or
      attractiveness genes for their offspring. A number of studies have demonstrated a
      positive relationship between paternal attractiveness and offspring quality.
      However, this pattern could be due to inheritance of paternal genes and/or it
      could be due to increased maternal investment in the offspring of more attractive
      males. To isolate female responses to male appearance from paternal genetic
      effects, I housed female red junglefowl (Gallus gallus) with vasectomized
      (sterile) males and artificially inseminated them. Male junglefowl with larger
      combs are more attractive to females. Females laid more eggs when housed with a
      large-combed, as opposed to a small-combed, vasectomized mate. Neither egg volume
      nor offspring body condition was associated with comb size of the mother's
      vasectomized mate. Paternal genetics appeared important. Body condition and comb
      size were greater for the sons of large-combed sperm donor males. This is
      consistent with the hypothesis that genetic benefits to offspring maintain female
      preference for the most ornate males. It is possible that greater body condition
      and comb size in sons of large-combed sires was not caused by genetic
      differences, but instead was due to compounds in the ejaculate of large-combed
      sperm donors inducing greater reproductive investment from females. However,
      females artificially inseminated by large-combed males did not produce more or
      larger eggs than females artificially inseminated by small-combed males, and thus
      there is no other evidence consistent with ejaculate-induced differential
      investment. Furthermore, only in older chicks was body condition significantly
      related to sire comb size, suggesting genetic rather than differential investment
      mechanisms.

PMID- 14575336
TI  - Diversification in sexual and asexual organisms.
AB  - Sexual reproduction has long been proposed as a major factor explaining the
      existence of species and species diversity. Yet, the importance of sex for
      diversification remains obscure because of a lack of critical theory,
      difficulties of applying universal concepts of species and speciation, and above
      all the scarcity of empirical tests. Here, we use genealogical theory to compare
      the relative tendency of strictly sexual and asexual organisms to diversify into
      discrete genotypic and morphological clusters. We conclude that asexuals are
      expected to display discrete clusters similar to those found in sexual organisms.
      Whether sexuals or asexuals display stronger clustering depends on a number of
      factors, but in at least some scenarios asexuals should display a stronger
      pattern. Confounding factors aside, the only explanation we identify for stronger
      patterns of diversification in sexuals than asexuals is if the faster rates of
      adaptive change conferred by sexual reproduction promote greater clustering.
      Quantitative comparisons of diversification in related sexual and asexual taxa
      are needed to resolve this issue. The answer should shed light not only on the
      importance of the different stages leading to diversification, but also on the
      adaptive consequences of sex, still largely unexplored from a macroevolutionary
      perspective.

PMID- 14575337
TI  - Phylogenetics of pond and lake lifestyles in Chaoborus midge larvae.
AB  - Aquatic invertebrates experience strong trade-offs between habitats due to the
      selective effects of different predators. Diel vertical migration and small body
      size are thought to be effective strategies against fish predation in lakes. In
      the absence of fish in small ponds, migration is ineffective against invertebrate
      predators and large body size is an advantage. Although widely discussed, this
      phenomenon has never been tested in a phylogenetic context. We reconstructed a
      mitochondrial DNA (mtDNA) tree to investigate the phylogenetic distribution of
      pond and lake lifestyles among 10 species of northern temperate Chaoborus midge
      larvae. The mtDNA tree is similar to previous morphological trees for Chaoborus,
      the only difference being the disruption of the subgenus Chaoborus sensu stricto.
      At least three shifts have occurred between pond and lake lifestyles, each time
      associated with evolution of diel vertical migration in the lake taxon. The trend
      in larval body size with habitat type is sensitive to tree and character
      reconstruction methods, only weakly consistent with the effects of fish
      predation. Despite long time periods over which adaptation to each habitat type
      could have occurred, there remains significant phylogenetic heritability in
      larval body size. The tree provides a framework for comparative studies of the
      metapopulation genetic consequences of pond and lake lifestyles.

PMID- 14575338
TI  - Queen size mediates queen survival and colony fitness in harvester ants.
AB  - We examined the effect of queen size on the probability of new colony
      establishment in the ant Pogonomyrmex occidentalis. Large queens are
      significantly more likely to survive than small queens through the initial stages
      of colony founding. These differences in individual fitness correlates have
      corresponding effects on colony fitness. In species in which individual queens
      vary in fitness, sexual allocation ratios should incorporate the individual
      fitness functions.

PMID- 14575339
TI  - Offspring size-number trade-offs in scorpions: an empirical test of the van
      Noordwijk and de Jong model.
AB  - Life-history traits are expected to exhibit negative phenotypic trade-offs, but
      often do not. In a seminal paper, van Noordwijk and de Jong (1986) provided an
      answer to this seeming paradox. According to their model, trade-offs will be more
      difficult to detect if variation in resource acquisition (or investment) is high
      relative to variation in resource allocation to the traits under consideration.
      Despite its influence on subsequent life-history studies, this model has rarely
      been tested. I use data from 10 species of scorpion (a total of 30 datasets,
      including multiple populations or years for some species) to test the van
      Noordwijk-de Jong model as modified to examine the relationship between offspring
      size and number. For both the overall data and a subset, including only the
      species Centruroides vittatus, I found that the correlation between offspring
      size and number within a population was significantly negatively correlated with
      the ratio of allocation variance to investment variance. That is, strong trade
      offs were found when the investment variance was low relative to the allocation
      variance. These results were robust to the particular measure of offspring size
      and to whether offspring data were adjusted for female size variation. My results
      therefore provide strong evidence in support of the van Noordwijk and de Jong
      model.

PMID- 14575340
TI  - Heritability of parental effort in a passerine bird.
AB  - The study of the evolution of parental care is central to our understanding of
      social systems, sexual selection, and interindividual conflict, yet we know
      virtually nothing about the genetic architecture of parental care traits in
      natural populations. In this paper, we use data from a long term field study of a
      passerine bird, the long-tailed tit (Aegithalos caudatus), to examine the
      heritability of the rate at which parents feed offspring. This measure of effort
      is positively related to offspring survival, is repeatable within individuals,
      and does not appear to be confounded by environmental effects. Using both parent
      offspring regression, and an animal model approach, with a pedigree derived from
      ringing data, we show that our measure of effort has a significant heritable
      component.

PMID- 14575341
TI  - Processing and linguistic markers in young children with specific language
      impairment (SLI).
AB  - Thirty-two 5-year-old children with specific language impairment (SLI) and 32
      chronological age (CA) controls completed 4 tasks that were considered potential
      positive markers for SLI. Children's performance on 2 linguistic tasks (past
      tense and noun plurals task) and 2 processing tasks (nonword repetition and digit
      recall) were examined. This approach allowed the examination of more than 1 type
      of marker simultaneously, facilitating both comparisons between markers and also
      the evaluation of combinations of markers in relation to identifying SLI.
      Children with SLI performed significantly worse than CA controls in all 4 marker
      tasks. Specificity/sensitivity analysis of the 4 marker tasks revealed nonword
      repetition and the past tense task to have the best overall accuracy at the 25th
      and 16th percentile. Finally, stepwise discriminant analysis revealed nonword
      repetition and past tense marking to be the best markers for identifying young
      children with SLI.

PMID- 14575342
TI  - Writing treatment for severe aphasia: who benefits?
AB  - Writing treatment that involved repeated copying and recall of target words was
      implemented with 8 individuals with severe aphasia in order to discern the best
      candidates for the treatment. Four of the 8 participants had strong positive
      responses to the copy and recall treatment (CART), relearning spellings for 15
      targeted words during 10 to 12 weeks of treatment and up to 5 additional words
      during a month-long homework-based program. Of the 4 other participants, 3
      learned the spellings of some target words but failed to reach criterion, and 1
      had a poor treatment outcome. Insights regarding possible factors that limited
      success were gained by examination of individual responses to treatment as well
      as performance on the pretreatment assessments of semantic, phonological, and
      orthographic processes. Among the factors associated with success were (a)
      consistent, accurate completion of daily homework, (b) a relatively preserved
      semantic system, (c) the ability to discern words from nonwords, and (d)
      adequately preserved nonverbal visual problem-solving skills. Aphasia severity
      and minimal pretreatment spelling abilities did not necessarily limit the
      response to treatment. Participants with positive treatment outcomes demonstrated
      improved spelling of target words following repeated copying within a single
      treatment session, and accurately completed daily writing homework. Thus,
      pretreatment assessment and stimulability within initial treatment sessions
      provided indications of likely outcome.

PMID- 14575343
TI  - Adjective definitions and the influence of word frequency.
AB  - The present investigation is a study of the development of adjective definitions
      given by participants in Grades 6 and 10 and by young adults, as well as the
      influence of word frequency on those definitions. A total of 150 participants (50
      per age group) wrote definitions for 6 high-frequency and 6 low-frequency
      adjectives. Adjective definitions were analyzed for use of semantic content and
      also grammatical form. Findings indicated that content of adjective definitions
      generally followed a developmental course from concrete and functional to more
      abstract. Response patterns of certain categories, such as superordinate, have
      implications for organization of the mental lexicon and suggest that adjective
      definitions may be less predictable than definitions of other grammatical
      categories, such as noun. Although conventional syntactic form was highly used in
      definitions (i.e., adjectival form for a definition of an adjective), verb form
      was also highly used. Conventional form may be less useful to characterize
      adjective definitions than other grammatical classes. Findings suggest that word
      frequency has a robust influence on adjective definitions and that development
      progresses differently for high- and low-frequency words.

PMID- 14575344
TI  - Outcomes of different speech and language goal attack strategies.
AB  - The purpose of this study was to assess phonological and morphosyntactic change
      in children with co-occurring speech and language impairments using different
      goal attack strategies. Participants included 47 preschoolers, ages 3;0
      (years;months) to 5;11, with impairments in both speech and language: 40 children
      in the experimental group and 7 in a no-treatment control group. Children in the
      experimental group were assigned at random to each of 4 different goal attack
      strategies: (a) in the phonology first condition, children received a 12-week
      block of phonological intervention followed by 12 weeks of work on morphosyntax;
      (b) the morphosyntax first condition was the same as phonology first, with the
      order of interventions reversed; (c) the alternating condition involved
      intervention on phonology and morphosyntax goals that alternated domains weekly;
      and (d) the simultaneous condition addressed phonological and morphosyntactic
      goals each session. Data were collected pretreatment, after the first
      intervention block, and posttreatment (after 24 weeks). For the control group,
      data were collected at the beginning and end of a period equivalent to 1
      intervention block. Change in a finite morpheme composite and target
      generalization phoneme composite was assessed. Results showed that
      morphosyntactic change was greatest for children receiving the alternating
      strategy after 24 weeks of intervention. No single goal attack strategy was
      superior in facilitating gains in phonological performance. These results provide
      preliminary evidence that alternating phonological and morphosyntactic goals may
      be preferable when children have co-occurring deficits in these domains; further
      research regarding cross-domain intervention outcomes is necessary.

PMID- 14575345
TI  - Children's productions of the affix -ed in past tense and past participle
      contexts.
AB  - Children's productions of the affix -ed in past tense and past participle
      contexts (e.g., the boy kicked the ball vs. the ball was kicked) were examined in
      spontaneous conversations and elicited productions. The performances of 7
      children with specific language impairment (SLI) were compared with those of 2
      control groups of typically developing children (age matches, MLU matches).
      Children with SLI produced fewer obligatory contexts for both past tense and past
      participle forms than did the control children, and were more likely to omit past
      tense affixes. In contrast, few omissions of the past participle were observed
      across all 3 groups. Implications for theories regarding the morphological
      deficits associated with SLI are discussed.

PMID- 14575346
TI  - The effectiveness of grammar instruction for individuals who use augmentative and
      alternative communication systems: a preliminary study.
AB  - This study examined the effectiveness of an instructional program designed to
      teach grammar skills to individuals who communicated via augmentative and
      alternative communication (AAC). A single-subject, multiple probe across
      behaviors design was used to measure the effect of the instructional program on
      the acquisition and maintenance of the skills learned. Two adults with cerebral
      palsy participated in the study. The instructional program was used to teach 2
      grammatical forms to each participant. Word order in adjective phrases and
      inversion of the auxiliary do in wh- questions was targeted for 1 participant;
      use of possessive pronouns and inclusion of to when using infinitives as modal
      verbs was targeted for the second participant. The instructional program was
      shown to be effective. Both participants learned to produce the grammatical forms
      taught. One participant maintained these skills for at least 2 months after the
      completion of instruction; the other participant required additional instruction
      in order to maintain the skills learned. Although based on a small sample, the
      results suggest that intervention can help individuals who use AAC improve their
      grammar skills. Limitations of the study are discussed, along with directions for
      future research.

PMID- 14575347
TI  - Auditory serial position effects in story retelling for non-brain-injured
      participants and persons with aphasia.
AB  - Using story retelling as an index of language ability, it is difficult to
      disambiguate comprehension and memory deficits. Collecting data on the serial
      position effect (SPE), however, illuminates the memory component. This study
      examined the SPE of the percentage of information units (%IU) produced in the
      connected speech samples of adults with aphasia and age-matched, non-brain
      injured (NBI) participants. The NBI participants produced significantly more
      direct and alternate IUs than participants with aphasia. Significant age and
      gender differences were found in subsamples of the NBI controls, with younger and
      female participants generating significantly more direct IUs than male and older
      NBI participants. Alternate IU productions did not generate an SPE from any
      group. There was a significant linear increase from the initial (primacy) to the
      final (recency) portion of the recalled alternate IUs for both the NBI group and
      the group of participants with aphasia. Results provide evidence that individuals
      with aphasia recall discourse length information using similar memory functions
      as the nonimpaired population, though at a reduced level of efficiency or
      quantity. A quadratic model is suggested for the recall of information directly
      recalled from discourse-length language material.

PMID- 14575348
TI  - Working memory capacity and language processes in children with specific language
      impairment.
AB  - This study examined the interaction between working memory and language
      comprehension in children with specific language impairment (SLI), focusing on
      the function of the central executive component and its interaction with the
      phonological loop (A. D. Baddeley, 1986) in complex working memory tasks.
      Thirteen children with SLI and 13 age-matched (age range = 7;0 [years;months] to
      10;0) children with typical language development participated. The tasks combined
      traditional nonword repetition tests and sentence comprehension by using
      sentences that differed in length and syntactic complexity. The children with SLI
      exhibited larger processing and attentional capacity limitations than their age
      matched peers. Increased word length and syntactic complexity resulted in a large
      performance decrease in nonword repetition in both groups. There were some
      variations in the error pattern, which may indicate qualitative differences
      between the 2 groups. The performance of the children with SLI in nonword
      repetition, across the different tasks, indicated a limitation in simultaneous
      processing rather than difficulty in encoding and analyzing the phonological
      structure of the nonwords. Furthermore, syntactic complexity had a greater effect
      on performance accuracy than did sentence length.

PMID- 14575349
TI  - A method for examining productivity of grammatical morphology in children with
      and without specific language impairment.
AB  - Children with specific language impairment (SLI) show inconsistent use of
      grammatical morphology. Children who are developing language typically also show
      a period during which they produce grammatical morphemes inconsistently. Various
      theories claim that both young typically developing children and children with
      SLI achieve correct production through memorization of some inflected forms (M.
      Gopnik, 1997; M. Tomasello, 2000a, 2000b). Adapting a method introduced by C.
      Miller and L. Leonard (1998), the authors investigated the use of present tense
      third singular -s by 24 typically developing preschoolers and 36 preschoolers
      with SLI. Each group was divided into 2 mean length of utterance (MLU) levels.
      Group and individual data provided little evidence that memorization could
      explain the correct productions of the third singular morpheme for either
      children with SLI or typically developing children, and there was no difference
      between children with higher and lower MLUs.

PMID- 14575350
TI  - Deaf adults without attention deficit hyperactivity disorder display reduced
      perceptual sensitivity and elevated impulsivity on the Test of Variables of
      Attention (T.O.V.A.).
AB  - The Test of Variables of Attention (T.O.V.A.; R. A. Leark, T. R. Dupuy, L. M.
      Greenberg, C. L. Corman, & C. L. Kindeschi, 1996) is a continuous performance
      test used widely to help diagnose attention deficit hyperactivity disorder (ADHD)
      in both hearing and deaf people. The T.O.V.A. previously has been normed only on
      the hearing population. The T.O.V.A. performance of 38 prelingually and severely
      to-profoundly deaf young adults and 34 hearing young adults who did not have ADHD
      was examined in this study. Deaf and hearing participants did not differ on the
      T.O.V.A. omission variables. However, deaf participants had significantly lower
      d' scores than hearing participants, indicating reduced perceptual sensitivity to
      the distinction between target and distractor stimuli. Consistent with the
      existing literature on attentional reorganization in the deaf population, this
      result was interpreted as indicating a deafness-related reduction in attention to
      centrally presented stimuli. Deaf participants also showed 2 to 3 times more
      commission errors than hearing participants and displayed a higher incidence of
      anticipatory errors. These results suggest a deafness-related increase in
      impulsivity at the time of response initiation. Beta score analysis confirmed
      that deaf participants adopted an overall less conservative (more impulsive)
      response criterion that contributed to their total elevated commission errors.
      However, a portion of the commission errors was secondary to their reduced d',
      not to increased behavioral impulsivity. Separate factor analyses of the standard
      T.O.V.A. variables revealed highly similar factor structures for deaf and hearing
      participants, indicating similar construct validity of the T.O.V.A. for both
      groups. The evidence for increased inattention and impulsivity in a non-ADHD deaf
      sample are interpreted in the context of an adaptive attentional reorganization
      due to deafness. Along with the factor analytic results, these considerations
      suggest that separate T.O.V.A. norms must be developed for the deaf population to
      avoid overdiagnosis of ADHD in deaf individuals.

PMID- 14575351
TI  - The influence of phonemic awareness development on acoustic cue weighting
      strategies in children's speech perception.
AB  - In speech perception, children give particular patterns of weight to different
      acoustic cues (their cue weighting). These patterns appear to change with
      increased linguistic experience. Previous speech perception research has found a
      positive correlation between more analytical cue weighting strategies and the
      ability to consciously think about and manipulate segment-sized units (phonemic
      awareness). That research did not, however, aim to address whether the relation
      is in any way causal or, if so, then in which direction possible causality might
      move. Causality in this relation could move in 1 of 2 ways: Either phonemic
      awareness development could impact on cue weighting strategies or changes in cue
      weighting could allow for the later development of phonemic awareness. The aim of
      this study was to follow the development of these 2 processes longitudinally to
      determine which of the above 2 possibilities was more likely. Five-year-old
      children were tested 3 times in 7 months on their cue weighting strategies for a
      /so/-/[symbol in text]o/ contrast, in which the 2 cues manipulated were the
      frequency of fricative spectrum and the frequency of vowel-onset formant
      transitions. The children were also tested at the same time on their phoneme
      segmentation and phoneme blending skills. Results showed that phonemic awareness
      skills tended to improve before cue weighting changed and that early phonemic
      awareness ability predicted later cue weighting strategies. These results suggest
      that the development of metaphonemic awareness may play some role in changes in
      cue weighting.

PMID- 14575352
TI  - Anxiety levels in people who stutter: a randomized population study.
AB  - The question of whether people who stutter are generally more anxious than people
      who do not stutter has not yet been resolved. One major methodological barrier to
      determining whether differences exist has been the type of stuttering sample
      used. Studies investigating anxiety levels of those who stutter have mostly
      assessed people referred to stuttering therapy clinics, which is arguably a
      biased sample. To date, no studies have been published that have measured the
      anxiety levels of people who stutter in the community using random selection
      procedures. Such a sample is more likely to be representative of the population
      of people who stutter. The present study involved a random selection and
      telephone interview of people in 4,689 households. The telephone respondent was
      given a description of stuttering and asked if any person living in their
      household stuttered. If yes, a number of corroborative questions were asked, and
      permission was requested to tape the speech of the person believed to stutter
      over the telephone. A definite case of stuttering was based on (a) a positive
      detection of stuttering from the tape and (b) at least one of the corroborative
      questions supporting the diagnosis. A total of 87 people were identified as
      definite cases of stuttering across all ages, and 63 participants who were 15
      years or older completed a trait anxiety questionnaire over the telephone. Mean
      trait anxiety levels were significantly higher than levels generally found in
      society, though differences were not large. Implications of these results are
      discussed.

PMID- 14575353
TI  - Respiratory and laryngeal responses to an oral air pressure bleed during speech.
AB  - Researchers have hypothesized that the respiratory and laryngeal speech
      subsystems would respond to an air pressure bleed, but these responses have not
      been empirically studied. The present study examined the nature of the responses
      of the respiratory and laryngeal subsystems to an air pressure bleed in order to
      provide information relevant to the nature of motor control for speech.
      Participants produced a syllable train consisting of 7 syllables of [pa] 10 times
      with and without an air pressure bleed in place. Acoustic, aerodynamic, and
      respiratory kinematic data were collected. In the bleed condition, peak intraoral
      air pressure and average oral airflow during the [a] were lower, lung and rib
      cage volume excursions were longer, and rib cage volume terminations were more
      negative. This study provides empirical data demonstrating a clear interaction
      among the speech subsystems. Both active and passive mechanisms are suggested by
      the subsystems' responses.

PMID- 14575354
TI  - Temperamental characteristics of young children who stutter.
AB  - The purpose of this investigation was to assess the temperamental characteristics
      of children who do (CWS) and do not (CWNS) stutter using a norm-referenced parent
      report questionnaire. Participants were 31 CWS and 31 CWNS between the ages of
      3;0 (years;months) and 5;4 (CWS: mean age = 48.03 months; CWNS: mean age = 48.58
      months). The CWS were matched by age (+/- 4 months), gender, and race to the
      CWNS. All participants had speech, language, and hearing development within
      normal limits, with the obvious exception of stuttering for CWS. Children's
      temperamental characteristics were determined using the Behavioral Style
      Questionnaire (BSQ; S. C. McDevitt & W. B. Carey, 1978), which was completed by
      each child's parents. Results, based on parent responses to the BSQ, indicated
      that CWS are more apt, when compared to CWNS, to exhibit temperamental profiles
      consistent with hypervigilance (i.e., less distractibility), nonadaptability to
      change, and irregular biological functions. Findings suggest that some
      temperamental characteristics differentiate CWS from CWNS and could conceivably
      contribute to the exacerbation, as well as maintenance, of their stuttering.

PMID- 14575355
TI  - Effects of concurrent motor, linguistic, or cognitive tasks on speech motor
      performance.
AB  - This study examined the influence of 3 different types of concurrent tasks on
      speech motor performance. The goal was to uncover potential differences in speech
      movements relating to the nature of the secondary task. Twenty young adults
      repeated sentences either with or without simultaneous distractor activities.
      These distractions included a motor task (putting together washers, nuts, and
      bolts), a linguistic task (generating verbs from nouns), and a cognitive task
      (performing mental arithmetic). Lip movement data collected during the
      experimental conditions revealed decreases in displacement and velocity during
      the motor task. The linguistic and cognitive tasks were associated with increased
      spatiotemporal variability and increases in the strength of the negative
      correlations between upper and lower lip displacements. These findings show that
      distractor tasks during speech can have a significant influence on several labial
      kinematic measures. This suggests that the balance of neural resources allocated
      to different aspects of human communication may shift according to situational
      demands.

PMID- 14575356
TI  - Interarticulator coordination in dysarthria: an X-ray microbeam study.
AB  - Articulatory discoordination is often said to be an important feature of the
      speech production disorder in dysarthria, but little experimental work has been
      done to identify and specify the coordination difficulties. The present study
      evaluated the coordination of labial and lingual gestures for /u/ production in
      persons with Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and
      in control participants. Both tongue backing/raising and reduction of the area
      enclosed by the lips can produce the characteristic low F2 of /u/. The timing of
      these articulatory gestures with respect to the acoustic target of a low F2 was
      inferred from X-ray microbeam data. Pellet motions of the tongue dorsum and lips
      revealed the timing of the lingual and labial gestures to be strongly linked
      together (synchronized), predictive of the temporal location of the lowest F2
      within the vocalic nucleus, and scaled proportionately to the overall vowel
      duration in control participants. Somewhat surprisingly, essentially the same
      findings were obtained in the speakers with dysarthria. These relationships were
      noisier among the speakers with dysarthria, but the global synchronization
      patterns applied to all 3 groups. Further analyses revealed the synchronization
      to be less well defined and more variable across speakers with ALS, as compared
      to speakers with PD and the controls. Results are discussed relative to concepts
      of coordination in dysarthria.

PMID- 14575357
TI  - Postmenopausal breast cancer risk in relation to sex steroid hormones, prolactin
      and SHBG (Sweden).
AB  - OBJECTIVE: High levels of sex steroid hormones and prolactin have been suggested
      to enhance breast cancer development. Low levels of SHBG may indicate high levels
      of (bio-available) steroid hormones. The present study investigates whether high
      levels of sex steroid hormones and prolactin, and/or low levels of SHBG, are
      associated with high breast cancer risk. METHODS: Blood samples were collected in
      about 65,000 women participating in two population-based prospective cohort
      studies in Sweden. Follow-up yielded 173 postmenopausal breast cancer cases who
      had not been exposed to HRT. Levels of estrone, estradiol, SHBG, FSH, prolactin,
      testosterone, androstenedione and DHEAs were analysed in cases and 438 controls.
      Logistic regression analysis yielded odds ratios (ORs), with 95% confidence
      intervals, adjusted for potential confounders. RESULTS: The risk of breast cancer
      was associated with the highest versus lowest quartiles of estrone, OR: 2.58
      (1.50-4.44), estradiol (dichotomised: high versus low) (1.73: 1.04-2.88), and
      testosterone (1.87: 1.08-3.25). High risks, although not statistically
      significant, were seen for androstenedione (1.58: 0.92-2.72) and DHEAs (1.62:
      0.89-2.72). No strong associations were seen between SHBG or prolactin and risk
      of breast cancer. CONCLUSIONS: High levels of estrone, estradiol, testosterone,
      and possibly androstenedione and DHEAs, in postmenopausal women are associated
      with a high risk of subsequent breast cancer.

PMID- 14575358
TI  - Reproductive factors in relation to breast cancer characterized by p53 protein
      expression (United States).
AB  - OBJECTIVE: To evaluate the potential etiologic heterogeneity of breast cancer by
      examining whether associations with reproductive and other personal
      characteristics differed by p53 protein expression status. METHODS: Data from the
      Carolina Breast Cancer Study, a population-based, case-control study of 861 cases
      and 790 controls, were utilized. Immunohistochemical staining for the p53 protein
      was performed on 638 archived tumor specimens; 46% of cases were classified as
      p53+. Two separate unconditional logistic regression models were used to
      calculate odds ratios (OR) and 95% confidence intervals (CI) for p53+ and p53-
      breast cancer relative to controls for reproductive and other personal
      characteristics. Analyses were performed separately for younger (< or = 45 years)
      and older (>45 years) women. RESULTS: Risk factor profiles largely overlapped for
      p53+ and p53- breast cancer, with the exception of oral contraceptive (OC) use
      among younger women and a family history of breast cancer. Prolonged OC use was
      more strongly associated with p53+ breast cancer [OR 3.1 (95% CI: 1.2-8.1) than
      p53- breast cancer (OR 1.3 (95% CI: 0.6-3.2)] among younger women only. A first
      degree family history of breast cancer was associated with p53+ breast cancer
      among younger women [OR 1.5 (95% CI: 1.0-2.2)] and older women [OR 1.4 (95% CI:
      0.9-2.3)], but not p53- breast cancer in either age-group. CONCLUSIONS: These
      results provide little evidence of breast cancer heterogeneity as classified by
      p53 expression status. However, although not statistically significant, OC use
      among younger women and family history of breast cancer may operate through a
      pathway involving p53 alterations to increase risk of breast cancer.

PMID- 14575359
TI  - Allergy and risk of breast cancer among young women (United States).
AB  - OBJECTIVE: To investigate the relationship between allergy and risk of breast
      cancer in women 45 years of age and younger. METHODS: Data were analyzed from a
      population-based case-control study of breast cancer in western Washington. Cases
      were women born after 1944 who were diagnosed with invasive breast cancer (n =
      747) between January 1983 and April 1990. Controls (n = 958) were similarly aged
      women ascertained through random-digit dialing. Cases and controls were
      interviewed about their history of doctor diagnosed allergies, including detailed
      information on the specific types of allergies and the age of onset. Using
      logistic regression we examined the associations between allergy history and
      breast cancer. RESULTS: A history of allergies was associated with a reduced risk
      of breast cancer for women older than 35 (odds ratio (OR) = 0.77; 95% confidence
      interval (CI) = 0.60-0.99), but not for women 35 years or younger (OR = 1.30; 95%
      CI = 0.94-1.81). There was little difference in effect when age of first allergy
      onset was examined. No specific type of allergy was associated with breast cancer
      risk. CONCLUSION: Our results provide some evidence that a history of allergy may
      be associated with a reduced risk of breast cancer for women who develop breast
      cancer between 35 and 45 years of age. Future studies are needed to verify the
      relationship between immune responses and breast cancer risk.

PMID- 14575360
TI  - Occupation and breast cancer in women 20-44 years of age (United States).
AB  - OBJECTIVE: To examine the relation between breast cancer risk and job history
      among women 20-44 years of age who participated in a multi-center, population
      based, case-control study. METHODS: Participants consisted of women newly
      diagnosed with breast cancer (1642) and controls identified by random-digit
      dialing (1494). Details about the three longest jobs were collected and coded by
      an industrial hygienist. Odds ratios and 95% confidence intervals were calculated
      and adjusted for age, study site, and other breast cancer risk factors. RESULTS:
      Several occupational and industrial categories were found to influence breast
      cancer risk. Stratification of the study population by parity revealed
      differences in breast cancer risk between the two groups for several occupational
      categories, including teachers, librarians or counselors (increased risk only
      among parous women) and natural scientists and mathematicians (decreased risk
      only among nulliparous women). CONCLUSIONS: This is among the first population
      based case-control studies to examine occupational history and breast cancer risk
      in young women, with the ability to consider a wide array of potential
      confounders, including reproductive characteristics. This study provides further
      evidence of an increased breast cancer risk for several occupations and
      industries. Other findings were not as strongly supported by previous
      investigations.

PMID- 14575361
TI  - No increased risk of non-Hodgkin's lymphoma with steroids, estrogens and
      psychotropics (Netherlands).
AB  - OBJECTIVE: Earlier studies with data on drug use from interview suggested that
      corticosteroids, estrogens and psychotropics may increase the risk of non
      Hodgkin's lymphoma (NHL). The objective of this case-control study with complete
      pharmacy records was to investigate whether these results could be reproduced.
      METHODS: Cases were all subjects aged 20 years and older in a population of
      approximately 300,000 residents in the Netherlands who were registered with an
      incident primary discharge diagnosis of NHL between January 1, 1991 and December
      31, 1998. Controls were matched to cases on sex, year of birth, community
      pharmacy, calendar period and total duration of medication history. Conditional
      logistic regression was used to evaluate the association between categories of
      cumulative drug use in days and the risk of NHL. RESULTS: 997 controls were
      matched to 251 cases of NHL that occurred during the study period. In
      multivariate analyses, there was no statistically significant risk increase of
      NHL after exposure to corticosteroids, estrogens or psychotropics. Moreover, long
      term use of benzodiazepines showed an unexpected statistically significant
      protective effect (OR 0.34; 95% confidence interval 0.18-0.64). CONCLUSIONS: In
      our population-based study, corticosteroids, estrogens and psychotropics were not
      associated with an increased risk of NHL.

PMID- 14575362
TI  - Prospective study of serum retinol, beta-carotene, beta-cryptoxanthin, and
      lutein/zeaxanthin and esophageal and gastric cancers in China.
AB  - OBJECTIVE: This study examined the relationship between pretrial serum
      concentrations of retinol, beta-carotene, beta-cryptoxanthin, and
      lutein/zeaxanthin and the subsequent risk of developing esophageal squamous cell
      carcinoma and gastric cardia or non-cardia adenocarcinoma in subjects selected
      from a randomized nutritional intervention trial in Linxian, China, a region with
      epidemic rates of esophageal and gastric cardia cancer. METHODS: We used a
      stratified case-cohort design to select cohort members for inclusion in this
      study. In all we measured serum concentrations of the above vitamins in 590
      esophageal, 395 gastric cardia, and 87 gastric non-cardia case subjects as well
      as in 1053 control subjects. Relative risks (RRs) were estimated using Cox
      proportional hazards models. RESULTS: Median values in our cohort were low for
      serum retinol (33.6 microg/dl), beta-carotene (4.3 microg/dl), and beta
      cryptoxanthin (3.5 microg/dl), but were high for lutein/zeaxanthin (40.0
      microg/dl). Gastric cardia cancer incidence fell 10% for each quartile increase
      in serum retinol (RR = 0.90, 95% CI = 0.83-0.99). For esophageal cancer, an
      inverse association with retinol levels was found only in male non-smokers (RR =
      0.79 per quartile increase, 95% CI = 0.63-0.99). For gastric non-cardia cancer,
      an inverse association was limited to subjects 50 years old or younger (RR = 0.58
      per quartile, 95% CI = 0.31-0.96). For beta-cryptoxanthin there was a borderline
      significant protective association for gastric non-cardia cancer (RR = 0.88 per
      quartile, 95% CI = 0.76-1.0). In contrast, we found the incidence of gastric non
      cardia cancer increased (RR = 1.2 per quartile, 95% CI = 1.0-1.3) with increasing
      concentration of serum lutein/zeaxanthin. CONCLUSIONS: In this population, we
      found that low retinol and high lutein/zeaxanthin concentrations increased the
      risks of gastric cardia and gastric non-cardia cancer respectively. We found that
      there were no strong associations between any of the other analytes and any of
      the cancer sites.

PMID- 14575363
TI  - Glycemic index and load and risk of upper aero-digestive tract neoplasms (Italy).
AB  - BACKGROUND: The ability of dietary carbohydrates to affect blood glucose and
      insulin levels by dietary carbohydrates is best measured by the glycemic index
      (GI) and glycemic load (GL) which have been directly associated with risk of
      several chronic conditions, including cancer. PATIENTS AND METHODS: Three case
      control studies were conducted between 1992 and 2000 in Italy. The first one
      included 598 hospital patients with incident, histologically confirmed oral and
      pharyngeal cancer and 1491 controls admitted to the same hospital networks for
      acute, non-neoplastic diseases; the second study included 304 subjects with
      squamous cell oesophageal cancer and 743 controls; the third one included 460
      cases with laryngeal cancer and 1088 controls. All subjects were interviewed
      using a validated food frequency questionnaire. RESULTS: The odds ratios (OR) of
      upper aero-digestive tract neoplasms for the highest versus the lowest quintile
      of dietary GI and GL were 1.5 (95% confidence interval [CI]: 1.1-2.0) and 1.8
      (95% CI: 1.1-2.9), respectively. The associations were in the same direction for
      various cancer sites. The ORs were apparently stronger in women, in those with
      high body mass index and reporting low alcohol consumption. CONCLUSIONS: This
      study supports the hypothesis that high dietary GI and GL are associated with
      cancers of the upper aero-digestive tract.

PMID- 14575364
TI  - A vision for cancer incidence surveillance in the United States.
AB  - A comprehensive framework for cancer surveillance should span the entire lifespan
      and be capable of providing information on risk, burden, disparity, cost, cancer
      care, survival, and death. Cancer incidence, the point in the continuum when an
      individual is diagnosed with cancer, has a strong, well-developed system to
      produce information about newly diagnosed cancer cases. However, in the future,
      this system must be enhanced and integrated with other cancer surveillance
      networks and other systems to provide timely information on the burden of newly
      diagnosed patients with respect to various cross-cutting population
      characteristics (e.g., social, economic, race/ethnic, urbanicity, or access to
      care) to define, monitor, and reduce incidence and various disparities noted
      among population groups. Collaboration in data collection, standard setting,
      surveillance activities, research, education and training, data use, and advocacy
      among all registries and national programs will be important to the continued
      success of the cancer incidence surveillance system. The cancer registry is an
      integral part of the infrastructure to reduce the burden of cancer, including the
      numbers of newly diagnosed cases.

PMID- 14575365
TI  - A prospective study of different types of hormone replacement therapy use and the
      risk of subsequent breast cancer: the women's health in the Lund area (WHILA)
      study (Sweden).
AB  - OBJECTIVES: Reports suggest that combined estrogen plus progestin hormone
      replacement therapy (HRT) confers a higher breast cancer risk than estrogen
      alone. We aimed to establish whether breast cancer risk depends on the type of
      HRT formula. METHODS: The cohort consisted of 6586 women, aged 50-64 years, from
      the Lund area, Sweden, with no reported breast cancer upon inclusion. We obtained
      information such as HRT use through a questionnaire between December 1995 and
      February 2000. New breast cancers were identified through the South Swedish tumor
      registry. RESULTS: Between inclusion and December 2001, 101 women developed
      breast cancer. Only ever use of the continuous combined estrogen plus progestin
      (CCEP) formula differed between cases and controls (45.2% versus 23.5%; p =
      0.000001). Compared with never users, exclusive CCEP users had the highest age
      adjusted hazard ratio HR 3.3 (95% CI: 1.9-5.6; p < 0.001), followed by users of
      CCEP in addition to other HRT formulas HR 2.8 (95% CI: 1.4-5.5; p = 0.003). No
      significant increase was seen in women who exclusively used other HRT formulas.
      CONCLUSION: Women who used CCEP had over three times the risk of developing
      breast cancer compared with never users and twice the risk compared with users of
      other types of HRT.

PMID- 14575366
TI  - Survival analysis of distant prostate cancer by decade (1973-1997) in the Detroit
      Metropolitan Surveillance, Epidemiology and End Results (SEER) Program registry:
      has outcome improved? (United States).
AB  - OBJECTIVE: The purpose of this study is to examine differences in survival after
      diagnosis with distant stage prostate cancer by decade of diagnosis. METHODS:
      Subjects are 3337 Caucasian and 1947 African-American men with newly diagnosed
      primary distant stage prostate cancer between 1973 and 1997, with follow-up
      through 2001, from the Detroit SEER registry. The proportion of men within each
      category of each variable of interest is calculated. Relative survival is used to
      examine survival patterns over time. Kaplan-Meier and Cox proportional hazard
      models are also used to examine the relationship between decade of diagnosis and
      survival between short term (< or = 24 months) and long term (> 24 months)
      survivors. RESULTS: Relative survival has increased over the past three decades
      although this trend is not statistically significant. Relative survival is
      similar by race and decreases with increasing grade of tumor. Survival for men
      living < or = 24 months after diagnosis is similar over time. However, for men
      living > 24 months after diagnosis, there is a significant difference over time
      (p < 0.0001). CONCLUSION(S): In general, relative survival has been improving
      over the past three decades. However, it is the long term survivors (> 24 months)
      that are the primary contributors to this difference in survival by decade of
      diagnosis.

PMID- 14575367
TI  - Alcohol use and risk of non-Hodgkin's lymphoma among Connecticut women (United
      States).
AB  - OBJECTIVE: Incidence rates of non-Hodgkin's lymphoma (NHL) have risen
      dramatically over the past several decades; however, the etiology of NHL remains
      largely unknown. Previous studies of the relationship between alcohol consumption
      and NHL have yielded conflicting results. Data from a population-based case
      control study among women in Connecticut were analyzed to determine the potential
      impact of alcohol consumption on risk of NHL. METHODS: The study included 601
      histologically confirmed, incident cases of NHL and 718 population-based
      controls. In-person interviews were administered using standardized, structured
      questionnaires to collect data on history of consumption for beer, wine, and
      liquor. RESULTS: When compared to non-drinkers, women who reported consumption of
      at least 12 drinks per year of any type of alcohol experienced slightly reduced
      risk of NHL (OR: 0.82; 95% CI: 0.65-1.04). Further stratification by alcohol type
      revealed that the inverse association was mainly limited to wine consumption (OR:
      0.75; 95% CI: 0.59-0.96), with no clear association for beer or liquor
      consumption. Risk of NHL was further reduced with increasing duration of wine
      consumption (p for linear trend = 0.02). Consumption of wine for greater than 40
      years was associated with approximately 40% reduction in risk (OR: 0.63; 95% CI:
      0.44-0.91). CONCLUSION: Our results are consistent with several recent
      epidemiologic studies that have also suggested an inverse association between
      wine consumption and risk of NHL. The reduction in risk of NHL associated with
      increased duration of wine consumption warrants further investigation in other
      populations.

PMID- 14575368
TI  - Melano-macrophage centres and their role in fish pathology.
AB  - Melano-macrophage centres, also known as macrophage aggregates, are distinctive
      groupings of pigment-containing cells within the tissues of heterothermic
      vertebrates. In fish they are normally located in the stroma of the haemopoietic
      tissue of the spleen and the kidney, although in amphibians and reptiles, and
      some fish, they are also found in the liver. They may also develop in association
      with chronic inflammatory lesions elsewhere in the body and during ovarian
      atresia. In higher teleosts, they often exist as complex discrete centres,
      containing lymphocytes and macrophages, and may be primitive analogues of the
      germinal centres of lymph nodes. Melano-macrophage centres usually contain a
      variety of pigments, including melanins, and these increase in range and volume
      in older fish or in the presence of cachectic disease. Melano-macrophage centres
      act as focal depositories for resistant intracellular bacteria, from which
      chronic infections may develop. Iron capture and storage in haemolytic diseases
      appears to be a primary function, but antigen trapping and presentation to
      lymphocytes, sequestration of products of cellular degradation and potentially
      toxic tissue materials, such as melanins, free radicals and catabolic breakdown
      products are among other functions that have been ascribed. Recent work suggests
      that they are a site of primary melanogenesis rather than mere storage. Melano
      macrophage centres increase in size or frequency in conditions of environmental
      stress and have been suggested as reliable biomarkers for water quality in terms
      of both deoxygenation and iatragenic chemical pollution.

PMID- 14575369
TI  - Relative resistance of Pacific salmon to infectious salmon anaemia virus.
AB  - Infectious salmon anaemia (ISA) is a major disease of Atlantic salmon, Salmo
      salar, caused by an orthomyxovirus (ISAV). Increases in global aquaculture and
      the international movement of fish made it important to determine if Pacific
      salmon are at risk. Steelhead trout, Oncorhynchus mykiss, and chum, O. keta,
      Chinook, O. tshawytscha, coho, O. kisutch, and Atlantic salmon were injected
      intraperitoneally with a high, medium, or low dose of a Norwegian strain of ISAV.
      In a second challenge, the same species, except chum salmon, were injected with a
      high dose of either a Canadian or the Norwegian strain. Average cumulative
      mortality of Atlantic salmon in trial 1 was 12% in the high dose group, 20% in
      the medium dose group and 16% in the low dose group. The average cumulative
      mortality of Atlantic salmon in trial 2 was 98%. No signs typical of ISA and no
      ISAV-related mortality occurred among any of the groups of Oncorhynchus spp. in
      either experiment, although ISAV was reisolated from some fish sampled at
      intervals post-challenge. The results indicate that while Oncorhynchus spp. are
      quite resistant to ISAV relative to Atlantic salmon, the potential for ISAV to
      adapt to Oncorhynchus spp. should not be ignored.

PMID- 14575370
TI  - Extra small virus-like particles (XSV) and nodavirus associated with whitish
      muscle disease in the giant freshwater prawn, Macrobrachium rosenbergii.
AB  - A disease of Macrobrachium rosenbergii, the giant freshwater prawn, farmed in
      China was recently recorded in Zhejiang, Jiangsu, Shanghai, Guangxi and Guangdong
      provinces. The clinical sign of the disease, which develops in post-larvae (PL),
      is a whitish appearance of the muscles, particularly noticeable in the abdomen.
      Mortalities may reach 100% in some hatcheries. Investigations by transmission
      electron microscopy after negative staining of diseased PL homogenates showed the
      presence of two types of viral particles: one, unenveloped, icosahedral in shape,
      26-27 nm in diameter, the second, much smaller, about 14-16 nm in diameter,
      designated extra small virus particle (XSV). The large virus has a genome with
      two pieces of ssRNA (RNA-1 and RNA-2), of 3 and 1.2 kb, respectively.
      Hybridization tests confirmed that this large virus is closely related to M.
      rosenbergii nodavirus (MrNV) which was isolated from diseased prawns in a
      hatchery in the French West Indies. Its very small size and hypothesized
      biochemical and biological characteristics suggest XSV is a new type of
      crustacean virus. As XSV has always been found associated with the larger virus
      (nodavirus) and is located in muscle and connective cells of diseased animals, it
      could be an autonomous virus, a helper-type virus or a satellite-like virus.

PMID- 14575371
TI  - Pathology and immunohistochemistry in three species of salmonids after
      experimental infection with Flavobacterium psychrophilum.
AB  - Rainbow trout, Oncorhynchus mykiss (Walbaum), sea trout, Salmo trutta L., and
      Atlantic salmon, Salmo salar L., were experimentally infected with Flavobacterium
      psychrophilum in order to evaluate any species differences in susceptibility to
      the bacterium. Furthermore, differences in pathological changes and distribution
      of the bacteria in internal organs were studied. The bacteria were injected
      intraperitoneally in two doses, high dose (Hd) 1 x 10(7) colony forming units
      (CFU) fish(-1) and low dose (Ld) 1 x 10(6) CFU fish(-1). The mortalities in the
      Ld groups varied between 0 and 7.5% and in the Hd groups between 55-70%. No
      significant differences in mortality between the species were recorded. Clinical
      signs and pathological findings were similar in the three species and in
      accordance with those of rainbow trout fry syndrome. Rainbow trout showed more
      pronounced lesions in the spleen compared with the other species. Necrosis of
      renal tubular epithelium and haematopoietic tissue was most prominent in rainbow
      trout and Atlantic salmon. Intracellular eosinophilic droplets in the kidney
      tubular epithelium were a prominent finding in rainbow trout and sea trout
      surviving the infection. The distribution of the bacteria in internal organs was
      similar in the three species, as studied with immunohistochemistry.

PMID- 14575372
TI  - A comparison of epidemiological patterns of salmon lice, Lepeophtheirus salmonis,
      infections on farmed Atlantic salmon, Salmo salar L., in Norway and Scotland.
AB  - This paper examines two large national data sets collected over several years and
      contrasts the patterns of sea lice, Lepeophtheirus salmonis (Kroyer, 1837),
      infections, the use of treatments and the occurrence of chalimus peaks between
      Norwegian and Scottish farms. Infection levels in Scotland were significantly
      higher in general over the period under study. For the chalimus stage group in
      the first quarter of the year, Norwegian mean abundance stayed below 10 lice per
      m2 while Scottish means reached 45 lice per m2 of fish skin per m3 of water. Both
      countries had more chalimus in summer than at other times of year, but in the
      last 3 months of the year Scottish fish had, on average, two to four times as
      many chalimus as Norwegian fish. Peaks of chalimus abundance were more frequent
      in Scotland, particularly in winter, but the most prominent peaks occurred in
      summer in both countries. In Scotland a marked mid-year build-up of mobile pre
      adult and adult stages was seen, and both countries showed a tendency for mobile
      counts on the second year fish to increase towards the end of the year. Scottish
      fish carried, on average, three times as many mobile lice per m2 of skin as
      Norwegian fish in the last 3 months of the year. The difference in lice loads was
      reflected in the greater use of veterinary medicines on Scottish farms. The
      higher infection levels in Scotland may be due to shallower and more enclosed
      water bodies used for farming, smaller and shallower pens, differences in sea
      water temperatures or in access to appropriate medication. The results highlight
      the importance of ensuring that effective veterinary medicines are available in
      the UK for the control of infection.

PMID- 14575373
TI  - Feed deprivation of channel catfish, Ictalurus punctatus (Rafinesque), influences
      organosomatic indices, chemical composition and susceptibility to Flavobacterium
      columnare.
AB  - Withholding feed has been suggested as a strategy to manage infectious disease of
      channel catfish, Ictalurus punctatus (Rafinesque). In a previous study, we
      demonstrated that deprivation of feed for as little as 7 days reduced innate
      resistance of catfish to Flavobacterium columnare. This study was conducted to
      evaluate the effect of feeding regimens [no feeding (NF), fed once every other
      day to satiation (FEOD) and fed once daily to satiation (FD)] on organosomatic
      indices, physiological changes and susceptibility of channel catfish to F.
      columnare. Fish that were not fed for 2 and 4 weeks had a significant increase (P
      < 0.05) in gutted weight:-wet weight ratio and decrease in other organosomatic
      indices [gut index (GI), mesenteric fat index (MFI) and hepatosomatic index
      (HSI)]. Haematology was not effected by feeding regimen except at week 4, when a
      significantly higher haemoglobin level was observed in the NF fish. Serum protein
      did not differ at week 2, but the level at week 4 of the NF fish (35.91 mg mL(
      1)) was significantly lower than that of the FD fish (41.77 mg mL(-1)).
      Significantly lower (P < 0.05) blood glucose (39.5 and 40.3 mg dL(-1)) and liver
      glycogen (1.7 and 1.8 mg g(-1)) were seen in the NF fish at weeks 2 and 4,
      respectively, as compared with blood glucose and liver glycogen levels of FD fish
      (67.5 and 92.8 mg dL(-1) and 46.5 and 52.6 mg g(-1) at weeks 2 and 4,
      respectively) and FEOD (82.8 and 85.5 mg dL(-1) and 45.1 and 51.4 mg g(-1) at
      weeks 2 and 4, respectively). Mortality in the NF fish caused by F. columnare
      (78%) was significantly higher (P < 0.05) than mortality in the FD and FEOD
      treatments (0.0 and 1.7%, respectively). Blood glucose and liver glycogen showed
      the same trend of low values for NF fish following challenge (week 6). Blood
      glucose, liver glycogen, GI and HSI are sensitive indicators for channel catfish
      deprived of feed (NF) for 4 weeks. Blood glucose and liver glycogen levels around
      40 mg dL(-1) and 2 mg g(-1), respectively, are indicative of starvation in
      juvenile channel catfish. Moreover, NF fish were susceptible to F. columnare
      infection. Thus, it is suggested that in the absence of natural food, juvenile
      channel catfish should be fed at least once every other day to apparent satiation
      to maintain normal physiological function and improve resistance to F. columnare.

PMID- 14575374
TI  - Spectral analysis: principle and clinical applications.
AB  - This review article describes the principle and clinical applications of spectral
      analysis. Spectral analysis provides a spectrum of the kinetic components which
      are involved in the regional uptake and partitioning of tracer from the blood to
      the tissue. This technique allows the tissue impulse response function to be
      derived with minimal modeling assumptions. Spectral analysis makes no a priori
      assumptions regarding the number of compartments or components required to
      describe the time course of tracer in the tissue. Spectral analysis can be
      applied to various dynamic data acquired by planar scintigraphy, single photon
      emission computed tomography (SPECT) or positron emission tomography (PET) as an
      alternative approach to compartment analysis. This analysis appears to be
      clinically useful, because it not only facilitates the interpretation of dynamic
      scintigraphic, SPECT or PET data, but also simplifies comparisons between regions
      and between subjects.

PMID- 14575375
TI  - Usefulness of technetium-99m hexamethylpropylene amine oxime lung scan to detect
      inhalation lung injury of patients with pulmonary symptoms/signs but negative
      chest radiograph and pulmonary function test findings after a fire accident--a
      preliminary report.
AB  - OBJECTIVE: In this study, we employed technetium-99m hexamethylpropylene amine
      oxime (99mTc HMPAO) lung scan to detect inhalation lung injury of patients after
      a fire accident. METHODS: Ten healthy men for controls and 10 male patients with
      pulmonary symptoms/signs from a fire accident were enrolled in this study for
      comparison. 99mTc HMPAO lung scan was performed in each control and patient, as
      well as the degree of pulmonary vascular endothelium damage was represented as
      lung/liver uptake ratios (L/L ratio). All of the controls and patients had no
      smoking histories. None of the controls and patients had positive findings of
      plain chest radiograph (CXR) and pulmonary function test (PFT). RESULTS: The
      results showed that significantly higher L/L ratio in the 10 patients (0.53 +/-
      0.07) than in the 10 controls (0.30 +/- 0.07) (the p value < 0.05). Using a cut
      off value of 0.40, all of the 10 patients had abnormally increased L/L ratios.
      CONCLUSIONS: We conclude that 99mTc HMPAO lung scan has the potential to be a
      sensitive, objective and noninvasive method to detect inhalation lung injury of
      patients with pulmonary symptoms/signs but negative CXR and PFT findings after a
      fire accident.

PMID- 14575376
TI  - Comparison of gallium-67 citrate and technetium-99m tetrofosmin scan to detect
      Hodgkin's disease.
AB  - OBJECTIVE: The purpose of this study was to compare the usefulness of gallium-67
      citrate (67Ga) and technetium-99m tetrofosmin (Tc-TF) scan to detect Hodgkin's
      disease (HD). METHODS: In this study, 24 patients with HD underwent 67Ga and Tc
      TF scan before receiving any therapy. RESULTS: 67Ga scan could detect HD in all
      24 (100%) patients. Tc-TF scan could detect HD in 22/24 (91.6%) patients, but it
      was false-negative in one case of infradiaphragmatic HD and in another case with
      chemotherapy resistance. There was no significant difference in detection
      sensitivity between 67Ga and Tc-TF scan. CONCLUSIONS: We conclude that Tc-TF scan
      can not replace conventional 67Ga scan to detect HD.

PMID- 14575377
TI  - The value of Tc-99m-tetrofosmin scintigraphy in the assessment of P-glycoprotein
      in patients with malignant bone and soft-tissue tumors.
AB  - P-glycoprotein (Pgp) overexpression has been shown to be correlated with
      resistance to chemotherapy in patients with malignant bone and soft-tissue
      tumors. The aim of our study was to investigate the role of 99mTc-tetrofosmin as
      a functional imaging agent reflecting Pgp expression in these tumors. METHODS:
      Twenty eight patients with various malignant bone and soft-tissue tumors were
      studied. Radionuclide angiography with 99mTc-tetrofosmin was done first and
      planar images were acquired at 15 min and 90 min postinjection. Vascular phase
      was evaluated visually on dynamic images, metabolic state was evaluated both
      visually and quantitatively on planar images. Quantitative analysis was performed
      by the calculation of tetrofosmin uptake in the lesion against background and
      percent washout rate (WR%) of the tracer. Immunohistochemical analysis of Pgp was
      performed on biopsy specimens and the degree of expression was graded from 0 to
      3. RESULTS: There was a positive correlation between the Pgp score and the
      washout rate of tetrofosmin (r = 0.73, p = 0.000). The mean washout rate of
      tetrofosmin from the lesions with Pgp expression (31.81 +/- 6.72) was found to be
      significantly higher than those of without Pgp expression (21 +/- 3.49) (p =
      0.000). No statistically significant correlation was found between 15 min and 90
      min uptake ratios (UR) of tetrofosmin and Pgp score (r = -0.10, p = 0.6 and r = 
      0.21, p = 0.2, respectively). When the cut-off value of 24.5 (according to ROC
      analysis) for the washout rate was used to discriminate the lesions with and
      without Pgp expression, the test yielded a sensitivity value of 87.5% with a
      specificity of 100%. CONCLUSIONS: In malignant bone and soft-tissue tumors, 99mTc
      tetrofosmin uptake were not related to Pgp overexpression. Pgp overexpression was
      found to be correlated with the washout rate of the tracer. 99mTc-tetrofosmin
      scintigraphy with washout analysis may not only be a useful method for evaluating
      Pgp overexpression but also its function.

PMID- 14575378
TI  - Evaluation of radioiodinated (-)-o-iodovesamicol as a radiotracer for mapping the
      vesicular acetylcholine transporter.
AB  - We evaluated the potencies of radioiodinated (-)-o-iodovesamicol [(-)-oIV] as a
      selective vesicular acetylcholine transporter (VAChT) mapping agent. (-)
      [125I]oIV exhibited significant accumulation (about 2.8% of the injected dose) in
      rat brain. The regional brain distribution of radioactivity was similar for both
      (-)-[125I]olV and (-)-[3H]vesamicol. The accumulation of (-)-[125I]oIV in the
      brain was significant reduced by post-administration of unlabeled vesamicol (0.5
      /micromol/kg(-1)) and (-)-oIV (0.5 micromol/kg(-1)). On the other hand, the post
      administration of sigma ligands hardly affected the accumulation of (-)-[125I]oIV
      in the brain. These studies showed that (-)-[125I]oIV, as well as [3H] vesamicol,
      bound to VAChT with high affinity in the rat brain. Furthermore, (-)-[125I]oIV
      binding in the ipsilateral cortex to the lesion was significantly reduced by
      17.0%, compared with that in the contralateral cortex in a unilateral NBM
      lesioned rat. These results suggested that radioiodinated (-)-oIV may potentially
      be useful for the diagnosis of cholinergic neurodegenerative disorders.

PMID- 14575379
TI  - Potential of an adenosine A2A receptor antagonist [11C]TMSX for myocardial
      imaging by positron emission tomography: a first human study.
AB  - In previous in vivo studies with mice, rats, cats and monkeys, we have
      demonstrated that [7-methyl-11C]-(E)-8-(3,4,5-trimethoxystyryl)- 1,3,7
      trimethylxanthine ([11C]TMSX) is a potential radioligand for mapping adenosine
      A2A receptors of the brain by positron emission tomography (PET). In the present
      study, we studied the potential of [11C]TMSX for myocardial imaging. Uptake of
      radioactivity by the heart was high and gradually decreased after an intravenous
      injection of [11C]TMSX into mice. In metabolite analysis, 54% and 76% of the
      radioactivity in plasma and heart, respectively, were present as the unchanged
      form of [11C]TMSX 60 min postinjection. The myocardial uptake was reduced by
      carrier-loading and by co-injection of an adenosine A2A antagonist CSC, but not
      by co-injection of an adenosine A1 antagonist DPCPX. Pretreatment with a high
      dose of a non-selective antagonist theophylline also reduced the myocardial
      uptake of [11C]TMSX. These findings demonstrate the specific binding of [11C]TMSX
      to adenosine A2A receptors in the heart. Finally we successfully performed the
      myocardial imaging by PET with [11C]TMSX in a normal volunteer. A graphical
      analysis by Logan plot supported the receptor-mediated uptake of [11C]TMSX.
      Peripherally [11C]TMSX was very stable in human: >90% of the radioactivity in
      plasma was detected as the unchanged form in a 60-min study. We concluded that
      [11C]TMSX PET has the potential for myocardial imaging.

PMID- 14575380
TI  - Thallium-201 brain SPECT to diagnose aggressiveness of meningiomas.
AB  - This investigation was conducted to determine the ability of 201Tl brain SPECT
      with respect to preoperative prediction of lesional aggressiveness of meningioma.
      Fifty-nine lesions in 42 patients were examined. Early (15 min) and late (3 h)
      SPECT were obtained. Early uptake ratio (ER; lesion to normal brain average count
      ratio), late uptake ratio (LR) and the ratio of LR to ER (L/E ratio) were
      calculated. Twenty-three lesions exhibited malignant features based on histologic
      or clinical course such as recurrence or skull invasion. Both ER and LR of
      malignant meningiomas were significantly higher than those in thirty-six benign
      lesions. Benign lesions were classified into two groups for further analysis:
      meningotheliomatous type, which is the most common histology, and benign lesions
      other than the meningotheliomatous (other benign) type. ER in other benign type
      was lower than the meningotheliomatous and the malignant type. LR afforded
      differentiation of the malignant type from the two benign types. These two benign
      types could be distinguished on the basis of the L/E ratio. These results
      indicate that high pre-operative ER and LR values in patients with meningioma are
      indicators of the aggressiveness of lesions, i.e., malignant meningioma,
      recurrence or skull invasion.

PMID- 14575381
TI  - What is the diagnosis? Temporomandibular joint (TMJ) ankylosis probably caused by
      ankylosing spondylitis (AS).

PMID- 14575382
TI  - Ionic interaction of [11C]-N,alpha-dimethylbenzylamine (DMBA) in rodent brain.
AB  - The [S] enantiomer of [11C]-N,alpha-dimethylbenzylamine (DMBA) was synthesized by
      N-methylation of [S]-alpha-methylbenzylamine, and its biodistribution in mice was
      measured. [11C]-[S]-DMBA was rapidly distributed into the brain, heart and lungs,
      and considerable long-term retention in the brain was observed. The radioactive
      metabolites in the plasma were analyzed by liquid chromatography. Kinetic
      analysis using unmetabolized [11C]DMBA in the plasma as the input function was
      performed employing a simplified two-compartment model. The estimated
      distribution volumes (DV) of [11C]DMBA in the brain and heart were 6.05 and 3.95,
      respectively. The right striatum of the rat brain was lesioned with ibotenic acid
      2 weeks before the tracer experiment. Both in vitro and in vivo autoragiographic
      studies were performed, and revealed significant reduction of the radioactivity
      levels in the lesioned striatum. On the other hand, the regional cerebral blood
      flow, as measured by [14C]iodoantipyrine, was not significantly altered in the
      lesioned striatum. These results indicate that the ionic binding component for
      DMBA exists mainly in neural cells rather than in glial cells. [11C]DMBA might be
      a useful radiotracer for detection of neural cell loss in the brain.

PMID- 14575383
TI  - Does supplementation of CT and MRI with gallium-67 SPECT improve the
      differentiation between benign and malignant tumors of the head and neck?
AB  - The objective of our study is to determine whether 67Ga SPECT can supplement CT
      and/or MRI diagnostic information by visual comparison of the two separate data
      sets in patients with head and neck tumors. METHODS: A total of 50 patients with
      head and neck tumors (benign: 19, malignant: 31) were entered in the study. Three
      board-certified radiologists who had practical experience in interpreting both
      head and neck CT/MRI and 67Ga SPECT images, participated as readers. All of the
      CT and/or MR images of each patient were shown to each reader first, who after
      they had finished interpreting them were shown the 67Ga SPECT images. They were
      asked to score each image on a 7-point scale for the likelihood of the presence
      or absence of malignancy. Histological or cytological evaluation was done in all
      cases, and the radiologic studies were correlated with these findings. RESULTS:
      Improvement of all three readers' performance was from 70.7% to 83.3% in the mean
      accuracy and from 0.790 to 0.921 in the mean Az value (p = 0.033, 0.163, 0.105 in
      the Az values) after they were shown the 67Ga SPECT images. CONCLUSIONS: 67Ga
      SPECT should substantially increase confidence in the diagnosis of head and neck
      tumors when CT and/or MRI do not permit differentiation between benign and
      malignant disease.

PMID- 14575384
TI  - Assessment of fatty acid metabolism in taxan-induced myocardial damage with
      iodine-123 BMIPP SPECT: comparative study with myocardial perfusion, left
      ventricular function, and histopathological findings.
AB  - We investigated myocardial fatty acid metabolism in taxan-induced myocardial
      damage in patients with advanced lung cancer. PATIENTS AND METHODS: Twenty-five
      patients with non-small-cell lung cancer were treated with taxan combined with
      carboplatin intravenously for three cycles. Myocardial SPECT imaging using 99mTc
      methoxyisobutyl isonitrile (MIBI) and 123I-15-(p-iodophenyl)-3-(R,S)
      methylpentadecanoic acid (BMIPP) was performed successively before and after
      chemotherapy. Regional uptake scores of BMIPP and MIBI were visually assessed and
      total uptake scores and the number of abnormal segments were calculated. Left
      ventricular ejection fraction (LVEF) was obtained by first-pass radionuclide
      angiocardiography using MIBI. Postmortem pathological examination was performed
      in 5 patients. RESULTS: Total BMIPP uptake scores after chemotherapy were
      significantly lower than those before chemotherapy (23.4 +/- 3.4 vs. 26.6 +/-
      0.8; p < 0.001). Mean LVEF showed a significant decrease after chemotherapy. Of
      the 25 patients, 4 exhibited a decrease in LVEF of more than 10%, 1 had a
      decrease in LVEF to below 50%, and 1 developed congestive heart failure. These 6
      patients had significant decreases in total BMIPP uptake scores and increases in
      the number of abnormal segments as compared with the other 19 patients.
      Histopathological examination of myocardial tissue showed interstitial edema and
      disarrayed myocardial cells. CONCLUSION: Taxan impairs myocardial fatty acid
      metabolism. 123I-BMIPP myocardial SPECT is useful for evaluating the
      cardiotoxicity induced by taxan.

PMID- 14575385
TI  - Asialoglycoprotein receptor concentration in tumor-bearing livers and its fate
      early after their sectorial resection.
AB  - The aim of the present study was to investigate asialoglycoprotein receptor (ASGP
      R) status in tumor-bearing livers and early after their sectorial resection
      employing 99mTc-DTPA-galactosyl human serum albumin (99mTc-GSA) dynamic SPECT.
      METHODS: Ten normal liver controls and 44 liver tumor patients who underwent
      sectorial hepatectomy were included in the study. 99mTc-GSA dynamic SPECT study
      was performed 7 +/- 3 d before (pre-operative) and 34 +/- 13 d after surgery
      (post-operative) in liver tumour patients. Pre- and post-operative parameters
      including hepatic functional volume and 99mTc-GSA clearance of unit hepatic
      functional volume, representing ASGP-R concentration, were measured. The sum of
      functional volume of the sectors uninvolved in hepatectomy was defined as
      residual functional volume. Subsequently, post-operative change in functional
      volume (the ratio of post-operative to residual functional volume), post
      operative change in 99mTc-GSA clearance of unit hepatic functional volume (the
      ratio of post- to pre-operative 99mTc-GSA clearance of unit hepatic functional
      volume) and percent resection of functional volume were calculated. RESULTS: Pre
      operative 99mTc-GSA clearance of unit hepatic functional volume in tumor-bearing
      livers was significantly lower than that in non-tumor bearing control liver. The
      ratio of post- to pre-operative 99mTc-GSA clearance of unit hepatic functional
      volume showed marked variation from 0.57 to 2.14, which negatively correlated
      with the percent resection of functional volume (r = -0.58, p < 0.0001). The
      ratio of post- to pre-operative 99mTc-GSA clearance of unit hepatic functional
      volume exhibited a negative correlation with the ratio of post-operative to
      estimated residual functional volume (r = -0.67, p < 0.0001). CONCLUSION: ASGP-R
      concentration is reduced in the presence of liver tumor. ASGP-R concentration
      reveals variable changes early after sectorial resection; the change negatively
      correlates with percent resection of hepatic functional volume. Post-operative
      change in ASGP-R concentration negatively correlates with change in functional
      volume.

PMID- 14575386
TI  - Hypothyroidism presenting as a hot pertechnetate nodule.
AB  - The authors report an uncommon finding of hot nodule on Tc-99m sodium
      pertechnetate thyroid scan in three patients with hypothyroidism. Data indicate
      that hypothyroidism is secondary to Hashimoto's disease (HD). There was a
      concordant aspect on I-131 scan in two; a nodular discrepancy (cold nodule with I
      131) was associated with the highest microsomal antibodies titer. The findings of
      thyroid scan and ultrasonographic findings indicate that hot nodules may be
      observed either on initial or advanced stages of HD. Color flow Doppler
      sonography, showed an absence of internal increase of vascularization. These data
      suggest that the observed hot nodules correspond to localized hyperplasia of the
      less diseased portions secondary to chronic stimulation by TSH.

PMID- 14575387
TI  - Discrepant uptake between fluorine-18 fluorodeoxy glucose and Tc-99m sestamibi in
      bronchioloalveolar cell carcinoma.
AB  - Several studies have shown the benefit of fluorine-18 fluorodeoxy glucose (FDG)
      imaging in the differentiation of solitary pulmonary nodules. The majority of
      malignant tumor have a higher glucose metabolic rate as compared to benign
      lesions. However, there is a considerable variety in glucose metabolic rate that
      depends on the aggressiveness and histological subtype of the tumor. Technetium
      99m sestamibi (MIBI) is another tumor imaging agent for SPECT. We present a case
      of bronchioloalveolar cell carcinoma with a false negative finding in FDG imaging
      and a positive finding in MIBI imaging. This case clearly indicates that the FDG
      uptake and MIBI uptake might provide different information regarding
      characteristics of lung cancer.

PMID- 14575388
TI  - Thallium-201 myocardial SPECT in a patient with mirror-image dextrocardia and
      left bundle branch block.
AB  - A 53-year-old male patient with a previous diagnosis of situs inversus with
      mirror-image dextrocardia underwent thallium-201 (Tl-201) stress-redistribution
      myocardial perfusion single photon emission computed tomography (SPECT).
      Electrocardiogram (ECG) obtained on right hemithorax revealed constant complete
      left bundle branch block. Tl-201 stress-redistribution SPECT images revealed
      abnormal perfusion with reversible ischemia in the anteroseptal, septal and
      inferoseptal walls. Coronary angiography performed 1 month after SPECT study was
      normal. This case illustrates that false positive reversible perfusion defects
      can be seen in patients with mirror-image dextrocardia associated with constant
      complete left bundle branch block. To our knowledge, this is the first reported
      case of mirror-image dextrocardia and constant complete left bundle branch block
      with false positive Tl-201 SPECT findings.

PMID- 14575389
TI  - Bile leakage after living donor liver transplantation demonstrated with
      hepatobiliary scan using 9mTc-PMT.
AB  - Although it is recognized that hepatobiliary scan is of value in assessing
      postoperative complications of biliary surgery or cadaveric whole liver
      transplantation, there have been few reports regarding its usefulness following
      living donor liver transplantation. We performed living donor liver
      transplantation in a patient with biliary cirrhosis due to hepatolithiasis, using
      a right lobe graft from her sister. On the 15th postoperative day, bile discharge
      appeared from the operative wound. The leakage point could not be identified by
      computed tomography and cholangiography from the biliary drainage catheter.
      Hepatobiliary scan with Tc-99m Sn-N-pyridoxyl-5-methyltryptophan (99mTc-PMT)
      demonstrated biliary extravasation from the left side of the anastomosis of the
      hepatico-jejunostomy, indicating biliary leakage from the anastomosis.
      Conservative therapy was continued because the radioisotope flowed smoothly into
      the reconstructed jejunum and the biliary drainage catheter, and the leakage was
      stopped on the 63th postoperative day. Hepatobiliary scan is useful in
      determining the therapeutic plan as well as detection of bile leakage and
      identification of leakage points after living donor liver transplantation.

PMID- 14575390
TI  - Imaging of adenosine A1 receptors in the human brain by positron emission
      tomography with [11C]MPDX.
AB  - We report the first clinical PET study using [1-methyl-11C]8-dicyclopropylmethyl
      1-methyl-3-propylxanthine ([11C]MPDX) for imaging adenosine A1 receptors in the
      human brain. The binding of [11C]MPDX evaluated quantitatively as the
      distribution volume by a graphical analysis was high in the striatum and
      thalamus, and low in the cerebellum. The distribution pattern of [11C]MPDX was
      coincident with that of adenosine A1 receptors in vitro reported previously, and
      was different from those of blood flow and [18F]FDG. The [11C]MPDX PET has the
      potential for mapping adenosine A1 receptors in the human brain.

PMID- 14575391
TI  - Assessment of left ventricular function using solid-state gamma camera equipped
      with a highly-sensitive collimator.
AB  - PURPOSE: The solid-state gamma camera 2020tc Imager (Digirad, CA) is now
      commercially available and has been clinically applied. The present study
      evaluates the feasibility of equilibrium radionuclide ventriculography (ERNV)
      within a 3 min period using this camera equipped with a highly sensitive
      collimator. MATERIALS AND METHODS: ERNV was performed from the best septal
      position (left anterior oblique view) in 20 patients with cardiac disease using a
      single detector anger-type gamma camera equipped with a low-energy, high
      resolution collimator. Immediately thereafter, we performed a second ERNV using
      the solid-state gamma camera equipped with a highly sensitive collimator.
      Acquisition periods were 10 and 3 min, respectively. RESULTS: Significantly more
      counts were collected from over the left ventricle with the solid-state gamma
      camera over 3 min than those with the anger-type gamma camera over 10 min (817.1
      +/- 387.8 k counts vs. 668.2 +/- 327.4 k counts, p < 0.01). The left ventricular
      ejection fraction obtained from ERNV data using the solid-state gamma camera
      correlated closely with those acquired by the anger-type gamma camera (r = 0.94,
      p < 0.0001, SEE = 5.93%). CONCLUSION: The results showed that the solid-state
      gamma camera could assess left ventricular function with excellent data
      collection efficiency and high reliability.

PMID- 14575392
TI  - The evolution of concepts of vestibular peripheral information processing: toward
      the dynamic, adaptive, parallel processing macular model.
AB  - In a letter to Robert Hooke, written on 5 February, 1675, Isaac Newton wrote "If
      I have seen further than certain other men it is by standing upon the shoulders
      of giants." In his context, Newton was referring to the work of Galileo and
      Kepler, who preceded him. However, every field has its own giants, those men and
      women who went before us and, often with few tools at their disposal, uncovered
      the facts that enabled later researchers to advance knowledge in a particular
      area. This review traces the history of the evolution of views from early giants
      in the field of vestibular research to modern concepts of vestibular organ
      organization and function. Emphasis will be placed on the mammalian maculae as
      peripheral processors of linear accelerations acting on the head. This review
      shows that early, correct findings were sometimes unfortunately disregarded,
      impeding later investigations into the structure and function of the vestibular
      organs. The central themes are that the macular organs are highly complex,
      dynamic, adaptive, distributed parallel processors of information, and that
      historical references can help us to understand our own place in advancing
      knowledge about their complicated structure and functions.

PMID- 14575393
TI  - Complications of neck dissection.

PMID- 14575394
TI  - Effect of superoxide dismutase and allopurinol on impulse noise-exposed guinea
      pigs--electrophysiological and biochemical study.
AB  - OBJECTIVE: To investigate the protective effect of two anti-reactive oxygen
      species (ROS) substances, copper-zinc superoxide dismutase (CuZn-SOD) and
      allopurinol, in impulse noise-exposed guinea pigs. MATERIAL AND METHODS:
      Allopurinol or CuZn-SOD were administered intraperitoneally before exposure to
      125 dB SPL noise centered at 2.0-3.0 kHz, with a repetition rate of 4/s, for 1.8
      h. Hearing thresholds were tested by means of electrocochleography after
      implanting the animals with permanent electrodes. The presence of lipoperoxides
      in the guinea pig cochleae exposed to noise-induced oxidative stress was
      determined by means of the dosage of malondialdhyde, evaluated by measuring the
      content of thiobarbituric acid reactive substances in perilymph samples. RESULTS:
      Acoustic stress induced ROS formation and both allopurinol and CuZn-SOD exerted a
      protective effect on the cochlea. Comparison of compound action potential
      thresholds in different animal groups showed that the temporary threshold shift
      was significantly lower in treated animals than in those without pharmacological
      protection. CONCLUSION: The protective effect of the antioxidant agents
      demonstrates that, even at a high level of impulse noise exposure, a metabolic
      mechanism of cochlear damage may still play an important role in noise-exposed
      sensorineural hearing loss.

PMID- 14575395
TI  - Middle ear gas exchange in the air phase.
AB  - OBJECTIVE: The rate of gas exchange between the tympanum and mastoid is important
      for middle ear pressure regulation. The best-studied model of middle ear pressure
      regulation is the cynomolgus monkey. The aim of this study was to determine the
      time required for the equilibration of tympanum and mastoid partial pressures for
      two inert gases, argon and helium, in cadaveric cynomolgus monkey middle ears.
      MATERIAL AND METHODS: In separate experiments on 5 air-dried temporal bones from
      monkeys, helium or argon was introduced into the tympanum to bring the total
      pressure to 300 mmH2O above ambient and the partial pressures of all relevant
      gases in the tympanum and mastoid were measured using mass spectrometry at 0, 1,
      3, 5, 10 or 15 min. RESULTS: The average ratios of tympanum:mastoid partial
      pressure at 0 min were 4.7 +/- 1.9 and 3.9 +/- 2.0 for helium and argon,
      respectively. By 5 min those ratios had decreased to 1.2 +/- 0.2 and 1.1 +/- 0.1,
      respectively, suggesting approximate equilibrium. CONCLUSIONS: Air-phase gas
      exchange between the tympanum and mastoid is rapid. Partial-pressure gradients
      across the middle ear will be dissipated quickly and are not an important
      contributor to middle ear pressure regulation in the studied model.

PMID- 14575396
TI  - Cochlear blood flow modifications induced by anaesthetic drugs in middle ear
      surgery: comparison between sevoflurane and propofol.
AB  - OBJECTIVE: Because it is necessary to maintain controlled hypotension during
      middle ear surgery in order to avoid bleeding and as it is known that cochlear
      blood flow (CBF) is related to blood pressure (BP), it is useful to evaluate CBF
      modifications induced by anaesthetics in order to prevent cochlear damage. The
      aim of this paper is to evaluate, using laser Doppler flowmetry, which
      anaesthetic drug, out of sevoflurane and propofol, has the smallest effect on
      CBF. MATERIAL AND METHODS: Twenty consenting adult patients scheduled for
      myringoplasty under general anaesthesia for simple tympanic membrane perforation
      were studied. Patients were divided into two groups: the first group was treated
      with sevoflurane and the second with propofol. For the first group, CBF
      measurement was carried out on three different occasions: (i) at a basal low drug
      dosage; (ii) having increased the drug dosage to a higher level; and (iii) having
      reduced the drug dosage to the basal low level again. For the second group, CBF
      measurement was carried out on three different occasions: (i) 10 min after
      injecting a bolus of propofol; (ii) immediately after a second propofol
      injection; and (iii) 10 min after a third injection of propofol. A probe was
      placed over the promontory in order to measure CBF levels. RESULTS: In the
      subjects treated with sevoflurane, after having increased the drug dosage, BP
      decreased significantly while CBF did not change significantly. In the subjects
      treated with propofol we recorded a significant reduction in BP, as well as a
      decrease in CBF. CONCLUSION: The results obtained show that sevoflurane has a
      hypotensive effect without modifying CBF, while propofol, although having a
      similar effect on BP to sevoflurane, has less of a protective effect on inner ear
      microcirculation.

PMID- 14575397
TI  - The vestibulospinal reflex in humans: effects on paraspinal muscle activity.
AB  - OBJECTIVE: To elucidate the electromyographic (EMG) patterns elicited in the
      superficial paraspinal muscles (sacrospinalis, ileocostalis lomborum, longissimus
      dorsi and splenium cervicis). MATERIAL AND METHODS: In normal subjects adapted to
      the dark and standing on a force platform, EMG patterns were elicited in the
      superficial paraspinal muscles by means of unilateral cold caloric stimulation of
      the labyrinth. RESULTS: Almost concomitantly with the occurrence of postural
      derangement of the subject's trunk and head, the EMG patterns of the paraspinal
      muscles on both sides showed significant and consistent changes. In particular,
      the paraspinal muscles ipsilateral to the stimulated side showed a significant
      reduction in activity, while the homologous muscles of the contralateral side
      markedly increased their activity, with a consistent delay in comparison to the
      contralateral muscles. Moreover, the EMG changes occurred in a hierarchic fashion
      in the caudal-rostral direction. In fact, the more powerful and longer-lasting
      effects were consistently observed in the more caudal muscles, i.e. the
      sacrospinalis and ileocostalis, while the effects on the longissimus dorsi and
      splenium cervicis muscles were weak and inconsistent. CONCLUSION: These results
      suggest a possible use for the EMG patterns resulting from unilateral cold
      caloric stimulation for clinical evaluation of the vestibulospinal reflex.

PMID- 14575398
TI  - Music perception in adult cochlear implant recipients.
AB  - OBJECTIVE: To evaluate musical perception in adult cochlear implant (CI)
      recipients, i.e. perceptual accuracy for pitch, timbre, rhythmic patterns and
      song identification. MATERIAL AND METHODS: Twenty-nine adult patients were
      included in this transverse single-center study. Evaluative measures included
      tests assessing ability to discriminate pitch, rhythm and timbre and to identify
      nursery songs with and without verbal cues. Performance scores were correlated
      with duration of deafness, duration of implantation, speech discrimination and
      musical perception skills. RESULTS: A total of 38% of patients reported that they
      did not enjoy listening to music with their device and 86% presented lower scores
      of listening habits after implantation. We found positive correlations between
      musical background and pitch identification and identification of nursery songs
      played by piano. We also found positive correlations between speech
      discrimination and rhythm, timbre and identification of nursery songs with verbal
      cues. CONCLUSION: Trends in the patterns of correlation between speech and music
      perception suggest that music patterns are differentially accessible to CI users.
      New processing strategies may improve this.

PMID- 14575399
TI  - Progressive hearing loss after closed head injury: a predictable outcome?
AB  - OBJECTIVES: To evaluate the prevalence of progression of closed head injury (CHI)
      induced hearing impairment, defined as > or = 15 dB HL deterioration at 1 or more
      frequencies, and to identify risk factors in patient history and initial status
      that could predict progression. MATERIAL AND METHODS: A total of 600 patients
      with major CHI were admitted to 2 Swedish medical centres during a 14-year
      period. The type of injury was established by means of CT and the severity of
      head injury was measured using the Swedish Reaction Level Scale (RLS). In 62 of
      these patients, pure-tone audiometry was performed soon after the injury. Forty
      three patients agreed to participate in the present investigation, which was
      carried out 2-13 years after the injury. Each participant was evaluated using
      pure-tone audiometry and an itemized anamnesis was obtained. RESULTS: There was a
      higher prevalence of hearing impairments in the study group compared to a control
      group. Thirty-two subjects (74%,) showed a progression of > or = 15 dB, which was
      significantly greater than the spontaneous progression in the control group. Age
      and temporal bone fracture were risk factors for progression but not brain
      contusion only or RLS. There was an association between early pure-tone average
      (PTA) and progression as well as regression, i.e. the poorer the initial PTA the
      greater the progression as well as regression, indicating increased instability
      in the auditory system. Examination of patient histories did not reveal any
      single risk factors for progression. A serendipitous finding was a higher
      prevalence of reported memory shortcomings among those with post-traumatic
      tinnitus. CONCLUSION: Especially for those with fracture of the temporal bone the
      present results stress the importance of audiometric evaluation and follow-up,
      from both rehabilitation and medicolegal perspectives,

PMID- 14575400
TI  - Help-seeking behaviour of hearing-impaired persons aged > or = 55 years; effect
      of complaints, significant others and hearing aid image.
AB  - OBJECTIVE: To determine factors influencing help-seeking behaviour in hearing
      impaired persons aged > or = 55 years MATERIAL AND METHODS: The study comprised
      1,419 persons (480 females, 939 males) aged > or = 55 years who participated
      voluntarily in a driving test. Pure-tone audiometry was performed in all
      subjects. Participants without a hearing aid with an average hearing loss of > or
      = 30 dB in the better ear for the frequencies 0.5, 1, 2 and 4 kHz were asked how
      they perceived their hearing by means of a structured questionnaire. The
      questionnaire provided insight into why some hearing-impaired people seek help
      from a general practitioner (GP) and others do not. Four factors were examined.
      RESULTS: A total of 483/1.419 (34%) participants tested had a hearing loss
      exceeding 30 dB. Fewer than half of these had visited their GP with complaints of
      hearing impairment. Of those who had not sought help from a GP, 57% nevertheless
      judged their hearing as poor. Social pressure exerted by significant others was
      less in the non-consulters group. Hearing aid image did not differ significantly
      between the two groups. CONCLUSION: The help-seeking behaviour of hearing
      impaired elderly people is related to the degree of hearing disability and the
      social pressure exerted by significant others as well as the willingness to try
      hearing aids.

PMID- 14575401
TI  - Nasal mucosal temperature after exposure to cold, dry air and hot, humid air.
AB  - OBJECTIVE: To determine the influence of variations in the temperature and
      humidity of inhaled air on the nasal mucosal temperature at various sites in the
      nasal airways. MATERIAL AND METHODS: Fifteen volunteers were enrolled in the
      study. The temperature was measured on the mucosal surface of the nasal septum at
      the level of the nasal vestibule, in the nasal valve area, anterior turbinate
      area and choanae. Temperature measurements were made using a miniaturized
      thermocouple. Continuous temperature readings were performed before and after 10
      min of exposure to either cold, dry air, ambient air or hot, humid air. RESULTS:
      Inhalation of cold, dry air significantly reduced the temperature of the septal
      mucosa at each location of measurement compared to the breathing of ambient air.
      Inhalation of hot, humid air significantly increased the septal mucosal
      temperature at all detection sites CONCLUSIONS: The climatic condition of inhaled
      air can lead to significant changes in nasal mucosal temperature. As the nasal
      mucosa is important for nasal air conditioning, short-term exposure to air of
      extreme temperature and humidity can rapidly compromise nasal air conditioning.

PMID- 14575402
TI  - Expression of non-steroidal anti-inflammatory drug-activated gene-1 in human
      nasal mucosa and cultured nasal epithelial cells: a preliminary investigation.
AB  - OBJECTIVE: Non-steroidal anti-inflammatory drug-activated gene-1 (NAG-1) is a
      recently discovered transforming growth factor-beta superfamily cytokine. The
      localization and functions of NAG-1 have not been thoroughly studied. The aims of
      this study were to investigate its expression and localization in human nasal
      mucosa and also the change in NAG-1 expression as a function of mucociliary and
      squamous differentiation. MATERIAL AND METHODS: Anterior and middle portions of
      human inferior turbinate were used and immunohistochemical studies were performed
      using NAG-1 antibody. Passage-2 normal human nasal epithelial (NHNE) cell culture
      was performed for 14 days using the air-liquid interface method and the cells
      were divided into retinoic acid (RA)-sufficient and -deficient groups. Each group
      of cells was stained with hematoxylin-eosin to study the degree of
      differentiation. Western blot analysis for NAG-1 expression was performed in each
      group after 0, 7 and 14 days. RESULTS: NAG-1 expression in mucociliated
      epithelium was noted in ciliated cells and serous acini, but was not found in
      goblet cells or mucous acini. In squamous epithelium, NAG-1 expression was weaker
      than that in mucociliated epithelium. In RA-sufficient culture, NHNE cells were
      differentiated into ciliated epithelium, but in RA-deficient culture,
      keratinizing squamous epithelium was noted. Western blot analysis showed that NAG
      1 expression was significantly higher in RA-sufficient than -deficient culture
      (three-fold difference) and this expression was time-dependent. CONCLUSIONS: NAG
      1 may be involved in differentiation and apoptotic processes of nasal epithelial
      cells. However, it is still unclear whether NAG-1 is an inducer or a byproduct of
      differentiation or apoptosis. The role of NAG-1 protein remains to be solved.

PMID- 14575403
TI  - Placebo-controlled, randomized, double-blind study evaluating the efficacy of
      fluticasone propionate nasal spray for the treatment of patients with
      hyposmia/anosmia.
AB  - OBJECTIVE: To compare the effect on olfaction of topical glucocorticoid treatment
      versus placebo given for an extended period in addition to oral short-term
      glucocorticoids in patients with anosmia/hyposmia. MATERIAL AND METHODS: This was
      a randomized, double-blind, placebo-controlled study. The criterion for inclusion
      in the blinded phase was an improvement of at least 2 steps in the butanol odor
      threshold test following open treatment for 10 days with oral and nasal
      corticosteroids. Forty patients were included: 20 were randomized to treatment
      with fluticasone propionate, 10 to placebo and 10 others as controls. The topical
      treatment was continued for 6 months. RESULTS: The 3 groups showed similar
      improvements in their sense of smell after the initial 10-day treatment with
      combined oral and nasal corticosteroids. Patients who continued the local
      treatment maintained the same level of improvement throughout the study, whether
      or not they had been given nasal corticosteroids or placebo. We found no
      significant differences between the treatment groups. CONCLUSIONS: In patients
      with anosmia/hyposmia partly caused by local inflammation, no further improvement
      in the olfactory threshold is achieved by continuing with a topical intranasal
      glucocorticoid after an initial combined topical and systemic glucocorticoid
      treatment.

PMID- 14575404
TI  - Organized hematoma of the maxillary sinus.
AB  - OBJECTIVE: Organized hematoma of the maxillary sinus can develop by means of
      organization of hematoma in the unaerated maxillary sinus. To our knowledge, this
      is only the second article describing organized hematoma in the maxillary sinus.
      MATERIAL AND METHODS: We have observed eight cases of organized hematoma of the
      maxillary sinus recently and here we describe the clinical features (using CT
      scans and medical records), radiologic characteristics and pathologic findings.
      RESULTS: The patients comprised five males and three females (mean age 58 years),
      all of whom had a history of frequent epistaxis. They also complained of nasal
      obstruction, hyposmia, headache and swollen cheeks. Rhinoscopy revealed
      obliterated nasal cavities due to bulging lateral walls. CT scans showed soft
      tissue densities expanding the maxillary sinus into the nasal cavity. The
      treatment modalities used (applied either alone or in combination) were Denker's
      operation, Caldwell-Luc's operation and endonasal endoscopic surgery, and the
      outcomes were successful. CONCLUSION: Organized hematoma should be included in
      the differential diagnosis when patients have frequent epistaxis and an expansile
      mass in the maxillary sinus.

PMID- 14575405
TI  - Does the tonsillar surface flora differ in children with and without tonsillar
      disease?
AB  - OBJECTIVE: To investigate whether the tonsillar flora differ in children with and
      without adenotonsillar disease. MATERIAL AND METHODS: Tonsil surface swabs were
      taken from 218 children indicated for adenotonsillectomy because of moderate
      symptoms of recurrent tonsillopharyngitis or adenotonsillar hypertrophy (T+Ads
      group). Control swabs were taken from 100 children without symptoms of
      adenotonsillar disease who visited the ophthalmology clinic. Potential
      respiratory pathogens were identified. RESULTS: Potential respiratory pathogens
      were found in 54% of the T+Ads group, compared to 41% of the control group (p =
      0.04). Haemophilus influenzae was the commonest pathogen in both groups, being
      found in 41% of the T+Ads group and 34% of the control group. Moraxella
      catarrhalis was found more often in the T+Ads group compared to the control
      group: 7% vs 0% (p = 0.004). H. influenzae was found in 32% of the children with
      recurrent tonsillitis, compared to 48% of the children with symptoms of tonsillar
      hypertrophy (p = 0.03). CONCLUSIONS: The prevalence of potential respiratory
      pathogens on the tonsillar surface of children with moderate symptoms of
      recurrent tonsillopharyngitis and/or tonsillar hypertrophy differs only slightly
      from that in children without symptoms of adenotonsillar disease. Variations in
      the microbial flora do not seem to play an essential role in the predisposition
      of these children to tonsillar disease.

PMID- 14575406
TI  - Fourth branchial pouch sinus with recurrent deep cervical abscesses successfully
      treated with trichloroacetic acid cauterization.
AB  - A previously healthy 13-year-old girl presented with a left-sided deep cervical
      abscess. A CT scan demonstrated an abscess in the lower neck, anterior to the
      common carotid artery. Treatment with i.v. antibiotics and incision drainage
      resolved the condition. A recurrence of the abscess 7 months later was treated
      identically. Further investigations with MRI showed a 2-3-mm wide, 10-mm long
      structure in the lateral aspect of the left thyroid lobe. A barium radiograph
      depicted a narrow, 20-mm long fistula originating from the left pharynx. At
      endoscopy a 2-3-mm wide opening was found at the left pyriform sinus apex. This,
      together with the radiological findings, verified the diagnosis of a 4th
      branchial pouch sinus. The recurrence of the abscess may have been due to
      contamination by infectious pharyngeal secretions. Although radical surgical
      excision is traditionally recommended for this condition a non-invasive
      treatment, namely chemocauterization with 40% trichloroacetic acid (TCA), was
      chosen in this case. Three cauterizations were needed to close the pyriform sinus
      opening. To date (Month 14) there has been no recurrence of the cervical
      abscesses. TCA chemocauterization seems to be a safe first-line treatment for
      patients with a pyriform sinus fistula.

PMID- 14575407
TI  - Aerodynamic measurements in medialization thyroplasty.
AB  - OBJECTIVE: External vocal fold medialization thyroplasty is a standard technique
      for improving voice, swallowing and breathing impairments due to insufficient
      glottal closure caused by either unilateral vocal fold paralysis or deficit of
      vocal fold tissue (i.e. as a result of cordectomy, scarring processes or sulcus
      glottidis). However, only scant information is available concerning the effect of
      the medialization thyroplasty on aerodynamic parameters. The aim of this study
      was to investigate the effect of vocal fold medialization thyroplasty on the
      degree of laryngeal stenosis using selected aerodynamic parameters. MATERIAL AND
      METHODS: Thirty patients (12 female, 18 male) underwent external vocal fold
      medialization with a titanium vocal fold medialization implant under local
      anesthesia supplemented by i.v. sedation. Pulmonary function tests were performed
      pre- and postoperatively and selected parameters were analyzed statistically.
      RESULTS: All patients reported improved self-control of breathing during
      speaking, laughing, coughing and physical activity. The postoperative values of
      the parameters tested showed no significant alteration in comparison to the
      preoperative data. CONCLUSIONS: The analysis of the aerodynamic findings
      indicated that the medialization procedure using an implant did not cause an
      increase in the laryngeal resistance.

PMID- 14575408
TI  - Re: Factors affecting recovery after acoustic neuroma resection by Cohen et al.

PMID- 14575409
TI  - Cecilie Greig memorial lecture 2002. Myocardial protection: an expanding or
      contracting discipline?
AB  - For the past thirty years cardiac surgeons have had a unique opportunity to study
      the consequences of myocardial ischemia and reperfusion. With the advent of an
      ability to intervene in acute myocardial syndromes, cardiologists have vigorously
      joined that effort as have fundamental scientists. Exogenous myocardial
      protective strategies have emerged as have novel strategies that take advantage
      of endogenous mechanisms of myocardial protection. As a consequence of improved
      myocardial protection, operative mortality and morbidity, in particular the low
      output syndrome, have diminished. However, despite important increases in the
      knowledge base referable to myocardial ischemia and reperfusion, major advances
      in myocardial protection have slowed in the past several years. This article
      explores potential untapped options for augmenting myocardial protection and
      focuses on the potential adverse interactions between cardiopulmonary bypass and
      myocardial protection as a prime target for future investigations leading to
      improved myocardial management during heart operations.

PMID- 14575410
TI  - Miniaturization in cardiopulmonary bypass.
AB  - Cardiopulmonary bypass (CPB) remains the key technology for more complex cardiac
      operations. The perfusion equipment used nowadays has seen tremendous progress
      since its introduction into clinical practice 50 years ago. However, overall, CPB
      is still far from perfect. Major haemodilution is not only a problem for red cell
      dependent gas transport, but also for the platelet and humeral factor-dependent
      coagulation, the protein-dependent intravascular oncotic pressure and so forth.
      Reduction of the priming volume through further miniaturization of CPB equipment
      is, therefore, the most obvious next step. A systematic approach needs to
      optimize all CPB components, including pumps, oxygenator/heat exchanger
      structures, filters, reservoirs, cardiotomy suction, tubings and cannulas. This
      report provides an update of already commercially available low prime perfusion
      devices (e.g., the CORx integrated pump-oxygenator) as well as promising
      prototypes like the smart suction system and the smartcanula.

PMID- 14575411
TI  - Does cardiopulmonary bypass still represent a good investment? The biomaterials
      perspective.
AB  - Cardiopulmonary (CPB) bypass is 50 years old this year, and has undergone
      considerable change in that time, particularly with regard to developing
      technology. However, in recent years the routine application of CPB, as the
      treatment of choice for patients undergoing reparative heart surgery, has been
      challenged by new, evolving techniques, particularly Off-Pump Coronary Artery
      Bypass (OPCAB) and stenting. This paper considers whether CPB still represents a
      sound investment prospect, with particular emphasis on the biomaterial
      developments currently taking place. Whilst we accept that routine application of
      CPB is shrinking under pressure from less invasive techniques, we suggest that
      this may represent an opportunity to deliever a more highly evolved perfusion to
      the core of very sick and complex patients who may not be suitable candidates for
      OPCAB or stenting. These patients will benefit from the application of new
      technologies currently under development, such as smaller perfusion circuits,
      improved biomaterial surfaces, smart membranes, and biosensor technology, all
      aimed at making clinical perfusion a safer and more predictable procedure for the
      patient. All things considered, we feel that CPB, although shrinking in absolute
      size, still represents a good investment.

PMID- 14575412
TI  - Mechanical circulatory support: state of the art and future perspectives.
AB  - Mechanical circulatory support (MCS) has been viewed, until recently, as a rescue
      therapy to be applied when all else fails. Not surprisingly, this has resulted in
      suboptimal outcomes. Fortunately, the perseverance of a few dedicated groups has
      produced improved outcomes and the concept of MCS as an elective therapy is now
      steadily gaining acceptance. This is particularly true in the postcardiotomy
      setting, where a large number of new options are now available. The recently
      completed REMATCH study has demonstrated the feasibility and efficacy of
      permanent MCS as a therapy for end-stage heart failure, despite a high rate of
      device complications. Donor availability is decreasing and biological solutions
      will not be available for many years. New generation implantable rotary pumps, a
      fully implantable left ventricular assist device and a total artificial heart are
      all undergoing clinical evaluation, and several new exciting designs are in
      preclinical evaluation. A new paradigm for the treatment of terminal heart
      failure is emerging, where an unpredictable and expensive medically managed death
      in an intensive care unit setting is being exchanged for a more predictable high
      cost, front-loaded therapy with management from the outpatient clinic. The
      perfusionist community has much to contribute to this emerging life support
      field, not only in the perioperative period, but also in providing ongoing
      technical support to hospital staff, recipients and their families.

PMID- 14575413
TI  - New technologies for respiratory assist.
AB  - "The artificial lung especially has lingered behind progress with artificial
      hearts and ventricular assist devices, not because the need for lungs has not
      been recognized, but because we have not had a full understanding of the
      engineering problems and the unique material requirements until recent years."
      Brack Hattler, MD PhD. The development from the first clinical use of
      haemodialysis over five decades ago to widespread chronic treatment took more
      than two decades. The histories of other artificial organ technologies, such as
      artificial hearts, follow similar long development paths. For five decades, due
      to a lack of technology, artificial lungs have been limited to use with a heart
      lung machine for cardiopulmonary bypass (CPB) or extracorporeal membrane
      oxygenation (ECMO). The advent of pumpless biocompatible artificial lungs will
      open new treatment options for patients with acute or chronic lung failure.

PMID- 14575414
TI  - Expanding the role of perfusionists in the era of new treatment options for
      cardiovascular disease.
AB  - Treatment for cardiovascular disease has dramatically changed the surgical
      patient population over the past 10 years. Advances in medical management and
      interventional cardiovascular procedures have delayed surgery in many adults, and
      the surgical pool has begun to decrease despite an aging population. This affects
      perfusionists in terms of new psychological and technical challenges, and has
      serious consequences and implications for the future of the profession. This
      study will review the changing patterns of diagnosis and treatment of
      cardiovascular disease in the USA over the past 10 years by examining the annual
      surgical procedure rates and correlating them with the number of practicing
      perfusionists and new student graduates. The purpose of this review is to project
      the future employment opportunities for perfusionists. The second part of the
      paper will look at the alternative roles perfusionists have expanded into as a
      result of changes in the treatment of cardiovascular disease. The results of an e
      mail survey of perfusionists will be presented to identify new applications of
      perfusion technology.

PMID- 14575415
TI  - The evolution of perfusion education in America.
AB  - Clinical cardiopulmonary perfusion has evolved significantly during its 50 years.
      The science, technology and educational processes related to cardiopulmonary
      bypass have undergone continual change and metamorphosis. Perfusionists were
      initially trained on the job or in the laboratory, but with the advent of
      myocardial revascularization and the explosion in cardiac surgery, the need for
      formal educational training programs became apparent. The American Society of
      Extracorporeal Technology began the arduous processes of credentialing and
      developing certification guidelines that have continued under the American Board
      of Cardiovascular Perfusion. Licensure has also been adopted in many states
      during the past 10 years where nearly 50% of all perfusionists are covered by
      some legislative act. One additonal challenge has been developing minimal
      standards in which perfusionists practice. The initial standards included the use
      of a checklist and have evolved to monitoring and recording the significant
      events and parameters of each clinical procedure. The education of perfusionists
      will continue to be a challenge related primarily to reduced fiscal resources,
      the applicant pool and the ever-changing demands for extracorporeal circulation
      services. According to demographic and census information, it is expected the
      overall number of cardiovascular interventions will increase dramatically towards
      the latter end of the current decade in the US. The question arises as to what
      role perfusionists will play, as treatment strategies continue to change. If the
      number of education programs and new graduates continue to decline, the total
      number of perfusionists will decline, especially as many senior perfusionists
      leave the field or retire. It may be difficult to predict the total number of
      cardiovascular interventions that will be required in the next several years.
      However, if the total number of cardiovascular interventions that require
      perfusion services increase as a function of the aging population and if the
      overall incidence of cardiovascular treatment does not change, it will be
      imperative that perfusion education ramp up and train more perfusionists to meet
      the supply and demand or a shortage of skilled personnel may develop.

PMID- 14575416
TI  - Tubulo-interstitial lesions in glomerulopathy. I. Pathogenesis.
AB  - Glomerulopathies (GLN) are at the focus of interest of nephropathologist. As the
      name implies, the glomeruli are most characteristically affected. Beside
      glomeruli, also tubules and interstitium are important participants in renal
      scarring. It is believed that its chief determinant is proteinuria. The presence
      of protein in the urine activates tubular epithelial cells and induces production
      of mediators, the most important being TGF-beta. Subsequently, the interstitial
      cells are activated and acquire the myofibroblast phenotype. The myofibroblasts
      produce and deposit connective tissue matrix, resulting in morphologically
      visible scarring.

PMID- 14575417
TI  - Immunohistochemical study of endothelin-1 (ET-1) in human acute renal allograft
      rejection.
AB  - Immunoperoxidase staining was carried out using monoclonal antibody against
      endothelin-1 on renal allograft biopsy specimens from thirty one patients with
      acute renal transplant rejection: Banff 97 score IA (n = 11), score IB (n = 10)
      and score IIA (n = 10). As a control 10 biopsy specimens of the kidneys removed
      because of trauma were used. Endothelin-1 immunostaining was investigated in the
      renal interstitial vasculature and tubular epithelium. In the normal kidney the
      immunoreactivity of endothelin-1 was demonstrated in vascular endothelial cells
      and tubular epithelial cells. The intensity of endothelin-1 staining in
      endothelial cells in renal allograft biopsies from patients with Banff score IA
      and IB was similar to controls. In biopsies with Banff score IIA a marked
      decrease in endothelin-1 immunostaining of endothelial cells was seen. Moreover,
      renal tubular epithelium from patients with acute allograft rejection with Banff
      score IB and IIA had elevated endothelin-1 immunoreactivity as compared with
      controls. The results showed altered endothelin-1 immunostaining in renal biopsy
      specimens in patients with acute transplant rejection. In acute
      tubulointerstitial rejection Banff IB and acute vascular rejection Banff IIA up
      regulation of endothelin-1 on tubular epithelial cells was present, meanwhile in
      acute vascular rejection diminished immunoreactivity of endothelin-1 on
      endothelial cells was noted. In conclusion, our study suggests that endothelin-1
      play an important role in renal tissue injury in acute tubulointerstitial and
      vascular allograft rejection.

PMID- 14575418
TI  - S-phase fraction and menopausal status as the most important prognostic factors
      of disease-free survival for node negative patients with breast cancer. A
      prospective study.
AB  - The aim of our study was to determine a prognostic value of DNA flow cytometry
      measurements performed on fresh breast cancer tissues, separately for patients'
      groups defined by nodal status, with special attention to histological type of
      tumor. Between 1993 and 1996 samples from 677 patients were analyzed and 457
      cases were included in the survival analysis. Two-hundred and nine patients from
      them were node negative (N0). The median time of follow-up was 74 months. In
      multivariate analysis of disease-free survival (DFS), S-phase fraction (SPF) and
      menopausal status were found to be independent prognostic parameters for N0
      group. A combination of this factors allowed us to distinguish three groups
      different in respect of the risk of recurrence. Our results showed that: 1. SPF
      and menopausal status could be prognostically valuable factors for DFS in N0
      breast cancer patients; 2. prognostic value of SPF and ploidy should be evaluated
      separately for each histological type of breast cancer.

PMID- 14575419
TI  - Usefulness of galectin-3 immunohistochemistry in differential diagnosis between
      thyroid follicular carcinoma and follicular adenoma.
AB  - Galectin-3 was primarily reported to be a marker distinguishing thyroid adenomas
      and carcinomas. To check the usefulness of anti-galectin-3 immunohistochemistry,
      we studied its expression in 42 follicular adenomas and 42 follicular carcinomas.
      Eight cases out of 42 follicular adenomas (19%) presented focal or diffuse
      galectin-3 immunoexpression. From 42 cases of follicular carcinomas, six cases
      did not present galectin-3 immunopositivity at all. Three of these cases were
      widely invasive (one with focal anaplastic feature and one oxyphilic), and three
      other ones were minimally invasive. Two other carcinoma cases had only small foci
      positive with galectin-3 antibody, thirteen cases presented positivity mostly
      restricted to peripheral part of the tumor and 21 cases possessed diffuse, strong
      reaction. Two adenomas presented galectin-3 positive foci, and these cells had
      light nuclear changes superficially suggesting follicular variant of papillary
      carcinoma, mostly because of nuclear clearing. In these tumors, adenoma diagnosis
      was supported by experts, but we can not exclude that they represent early phase
      of malignisation, although such theory needs to be prooved. Our study does not
      allow to use galectin-3 as a highly specific marker, differentiating between
      follicular benign and malignant tumor, although it may be used as an additive
      tool.

PMID- 14575420
TI  - Determination of basic fibroblast growth factor levels in serum of tumor-bearing
      BALB/c mice treated with photodynamic therapy.
AB  - In the present study we have checked whether photodynamic therapy (PDT) may
      influence concentration of basic Fibroblast Growth Factor (bFGF) in in vivo
      conditions. We have implanted malignant tumor, i.e. BFS1 fibrosarcoma into BALB/c
      mice and have them treated using well established photosensitizer,
      hematoporphyrin derivative and new compound, hydroxygallium (III) phthalocyanine
      tetrasulfonic acid tetrasodium salt, BON-6. The administration of those compounds
      was followed by light irradiation using a halogen lamp at proper wavelengths. Our
      results indicate that in vivo photodynamic therapy may cause a significant
      decrease in bFGF concentration and this phenomenon is accompanied by prolongation
      of survival of treated animals.

PMID- 14575421
TI  - EBV-positive gastric carcinomas in Poland.
AB  - Epstein-Barr virus plays a substantial role in numerous human neoplasms including
      gastric carcinoma, as proved recently. In our series EBV has been detected in
      five cases of forty (12.5%) gastric carcinomas. It may indicate that Poland is
      one of the countries with the highest EBV-induced gastric carcinoma incidence
      worldwide.

PMID- 14575422
TI  - Morphological lesions detected by light and electron microscopies in chronic type
      C hepatitis.
AB  - HCV infection results in chronic hepatitis in most patients. The mechanisms
      determining liver damage and the events that lead to a high rate of chronic
      hepatitis remain unclear. In present study, an attempt was made to sum up data on
      lesions in the liver in the course of chronic type C hepatitis including those of
      our own cases, because that pattern is still a matter of debate. Cell lesions
      detected by light microscopy are characteristic but not specific and included
      inflammatory lesions of low or moderate intensity and a mild extent of fibrosis
      in the liver. The common and most characteristic trait of chronic HCV infection
      involves lesions in hepatocyte nuclei. These changes involved swelling, altered
      shape, hyperchromasia, disturbed nuclear chromatin structure, enlarged and
      frequently multiple nucleoli and lesions of nuclear envelope. Complexes of
      tubules or branching fibrils of 20-30 nm in diameter were present in cell nuclei
      at electron microscope level. The nuclear lesions were accompanied in the same
      cells by changes in rough endoplasmic reticulum with long tubular structures or
      branching fibrills inside. Other cytoplasmic changes included mitochondrial
      lesions, numerous lipid vacuoles and free tubular structure of a highly
      osmophilic character. Cellular localisation of HCV proteins using
      immunocytochemical techniques remains to be a matter of studies. In most studies
      HCV proteins have been detected in the cytoplasm although some reports indicate
      nuclear localisation, especially of C protein. All our observations on
      morphological lesions in chronic type C hepatitis can generally confirm most of
      data of other authors, but the criteria of nuclear lesions defined at the
      ultrastructural level represent the original input of our studies. The studies
      using molecular biology techniques should be continued at the electron microscope
      level.

PMID- 14575423
TI  - Pathologist and HIV--are safe autopsies possible?
AB  - Pathologists are at particularly high risk for blood contamination and skin
      injuries, so they are vulnerable to blood borne pathogens, like HIV. This article
      describes the first and the only one documented case of occupational HIV
      transmission in the world concerning American pathologist. The factors increasing
      the risk of contracting infection during the autopsy on the patient who has died
      of AIDS are considered. World-known recommendations to follow in such autopsy are
      described. The importance of compliance with universal precautions and the
      necessity of knowledge of the post-exposure prophylaxis are pointed as a way to
      avoid HIV infection.

PMID- 14575424
TI  - Alveolar adenoma of the lung--a report of two cases.
AB  - The authors present two cases of an extremely rare alveolar adenoma of the lung
      in a 64-year old female and a 45-year old male surgical patients. The report is
      the first description of such a tumor in the Polish literature.

PMID- 14575425
TI  - Synchronous primary heart liposarcoma and papillary renal carcinoma--a case
      report.
AB  - A case of synchronous primary cardiac dedifferentiated liposarcoma and papillary
      renal carcinoma is presented. The occurrence of typical areas of round cell
      liposarcoma made the pathological diagnosis of the sarcoma relatively easy;
      however the neoplasm was not diagnosed correctly before the autopsy. Cardiac
      liposarcoma is a very rare primary malignant neoplasm and its diagnosis based on
      image procedures may be extremely difficult especially at non-advanced stage of
      disease.

PMID- 14575426
TI  - dd-diketopiperazines: antibiotics active against Vibrio anguillarum isolated from
      marine bacteria associated with cultures of Pecten maximus.
AB  - Bacterial strains CF-20 (CECT5719) and C-148 (CECT5718), isolated from cultures
      of larvae of molluscs, are shown to produce substances 1-5 with strong antibiotic
      activity against Vibrio anguillarum (MIC: 0.03-0.07 mug/mL) and identified as the
      dd-diketopiperazines cyclo(d)-Pro-(d)-Phe (1), cyclo(d)-Pro-(d)-Leu (2), cyclo(d)
      Pro-(d)-Val (3), cyclo(d)-Pro-(d)-Ile (4), and cyclo-trans-4-OH-(d)-Pro-(d)-Phe
      (5). Comparison with other stereoisomers indicates that inhibition of V.
      anguillarum is associated with the presence of at least one d-amino acid in the
      diketopiperazine system. This is the first time a series of dd-diketopiperazines
      has been isolated from a single natural source and their inhibitory activity
      against V. anguillarum described.

PMID- 14575428
TI  - Dammarane-type triterpenes from the Brazilian medicinal plant Cordia
      multispicata.
AB  - From the Brazilian medicinal plant Carucaa (Cordia multispicata), oleanane- and
      ursane-type triterpenoids were previously reported as anti-androgenic
      constituents of the plant. In this study, purification of the polar elements of
      the EtOAc-soluble fraction of the plant revealed nine novel dammarane-type
      triterpenes, named cordianols A-I (1-9) along with the known compound cordialin A
      (10). The structures of these new compounds were elucidated by means of spectral
      methods including HRFABMS, (1)H NMR, (13)C NMR, and 2D NMR (HMQC, HMBC, NOESY).
      Absolute configuration at C-23 of compound 7 was determined by an excitone
      chirality method. Some of these new compounds revealed a hemiketal structure on
      the A ring and a hydroxylated or epoxidated 20(22)-(E)-ene side chain and showed
      weak anti-androgenic activity.

PMID- 14575427
TI  - Annularins A-H: new polyketide metabolites from the freshwater aquatic fungus
      Annulatascus triseptatus.
AB  - Eight new polyketide metabolites, annularins A-H (1-8), along with the known
      compound (-)-(S)-p-hydroxyphenyllactic acid, were isolated from the organic
      extracts of the freshwater fungus Annulatascus triseptatus. Compounds 1-6 are
      3,4,5-trisubstituted alpha-pyrones, and the fused bicyclic pyrone-furanone system
      in annularin F (6) has not been reported previously among natural products.
      Compounds 7 and 8 are 3,4-disubstituted alpha,beta-unsaturated gamma-lactones.
      Annularins A (1), B (2), C (3), and F (6) exhibited antibacterial activity.

PMID- 14575429
TI  - Isolation and characterization of new epothilone analogues from recombinant
      Myxococcus xanthus fermentations.
AB  - Nine new epothilone analogues (6-8, 10, 11a, 11b, 12, 13, and 15) were isolated
      from fermentations of Myxococcus xanthus strains engineered with modified
      polyketide synthase genes. The epothilone structures were elucidated primarily
      through interpretation of 1D and 2D NMR data. 4-Desmethyl-10,11
      didehydroepothilone D (6) displayed activity against several tumor cell lines,
      including a multi-drug-resistant cell line.

PMID- 14575430
TI  - Novel oxylipin metabolites from the brown alga Eisenia bicyclis.
AB  - Nine novel oxylipin metabolites together with several known ones were isolated
      from the brown alga Eisenia bicyclis. Five (1-5) of them are ecklonialactone
      derivatives containing a chlorine or an iodine atom, and two (6 and 7) are
      cymathere type oxylipins with a lactone ring or a chlorine atom. The structures
      of these oxylipin metabolites were confirmed by NMR and mass spectroscopy and
      compared with spectral data in the literature. The postulated biosynthetic
      pathway of these metabolites is discussed.

PMID- 14575431
TI  - Cytotoxic and antimalarial beta-carboline alkaloids from the roots of Eurycoma
      longifolia.
AB  - Three new [n-pentyl beta-carboline-1-propionate (1), 5-hydroxymethyl-9
      methoxycanthin-6-one (2), and 1-hydroxy-9-methoxycanthin-6-one (3)] and 19 known
      beta-carboline alkaloids were isolated from the roots of Eurycoma longifolia. The
      new structures were determined by comprehensive analyses of their 1D and 2D NMR
      and mass spectral data and by chemical transformation. These compounds were
      screened for in vitro cytotoxic and antimalarial activities, and 9-methoxycanthin
      6-one (4) and canthin-6-one (5) demonstrated significant cytotoxicity against
      human lung cancer (A-549) and human breast cancer (MCF-7) cell lines.

PMID- 14575432
TI  - Serratene-type triterpenoids from Huperzia serrata.
AB  - Seven new and 15 known serratene-type triterpenoids were isolated from the whole
      plant of Huperzia serrata. The structures of these new triterpenoids were
      elucidated as 21alpha-hydroxyserrat-14-en-3beta-yl p-dihydrocoumarate (1),
      21alpha-hydroxyserrat-14-en-3beta-yl dihydrocaffeate (2), 21alpha-hydroxyserrat
      14-en-3beta-yl propanedioic acid monoester (3), 3alpha,21alpha-dihydroxyserrat-14
      en-24-oic acid (4), 16-oxo-3alpha,21beta-dihydroxyserrat-14-en-24-al (5), 16-oxo
      3alpha,21beta-dihydroxyserrat-14-en-24-oic acid (6), and 16-oxo-21beta
      hydroxyserrat-14-en-3alpha-yl acetate (7), respectively, by means of
      spectroscopic analysis.

PMID- 14575433
TI  - An anxiolytic-like effect of Ginkgo biloba extract and its constituent,
      ginkgolide-A, in mice.
AB  - The anxiolytic-like effects of Ginkgo biloba extract (GBE) and its four terpenoid
      components (ginkgolide-A, ginkgolide-B, ginkgolide-C, and bilobalide) were
      assessed using the elevated plus-maze test in mice. Administration of GBE as a
      single oral dose (0.5 or 1 g/kg, po) caused a state of suppressed motor activity
      and, thus, shortened the time spent in the open-sided arms. However, when GBE
      (0.063-1 g/kg, po) was administered daily for 7 days and the plus-maze test was
      carried out 24 h after the final administration, the time spent in the open-sided
      arms was prolonged, with the peak anxiolytic-like effect at 0.125 g/kg. A
      combination of seven-day administration of GBE (0.125 g/kg) and a single dose of
      diazepam (1 mg/ kg, po, 10 min before testing) enhanced the anxiolytic-like
      effect. Flumazenil (0.3 mg/kg, ip, 10 min before testing) blocked the effect of
      diazepam, but not of GBE. Daily administration of ginkgolide-A (1 or 2 mg/kg, po)
      resulted in an anxiolytic-like effect by the third treatment, with the maximal
      effect observed after the fifth administration. Neither ginkgolide-B, ginkgolide
      C, nor bilobalide produced any anxiolytic-like effects. At doses higher than 0.5
      g/kg, GBE not only inhibited motor activity but also suppressed active avoidance
      behavior, reduced caffeine-induced stimulation, and enhanced pentobarbital
      induced sleep, while ginkgolide-A (up to 20 mg/kg) did not exhibit these effects.
      Diazepam (1 mg/kg) is known to enhance pentobarbital-induced sleep. These results
      suggest that GBE produces a significant anxiolytic-like effect following repeated
      administration and that ginkgolide-A is most likely responsible for this effect.
      There are also indications that although GBE exerts a sedative effect at
      comparatively higher doses, ginkgolide-A has a relatively weak tendency to
      produce benzodiazepine-like side effects.

PMID- 14575434
TI  - Chemistry and structure-activity relationship of HIV-1 integrase inhibitor
      integracide B and related natural products.
AB  - Integracides, 4,4-dimethylergostane triterpenoids, are inhibitors of HIV-1
      integrase, a critical enzyme in replication of HIV-1. The chemistry and structure
      activity relationship of integracide B and related natural products are
      described. A charged group, e.g., a sulfate, carboxyl, or amino, is required for
      the HIV-1 integrase activity. These compounds showed HIV-1 integrase activity
      with IC(50) values in the range 4.8-15 muM and exhibited antiviral activity in a
      viral spread assay, but with only a small or no therapeutic window.

PMID- 14575435
TI  - Bioassay-guided isolation of epiquinamide, a novel quinolizidine alkaloid and
      nicotinic agonist from an Ecuadoran poison frog, Epipedobates tricolor.
AB  - Analytical HPLC fractionation, combined with an off-line 96-well fluorescent
      bioassay screen, has been developed and used for the separation and screening of
      a natural product extract. This method was used to guide the isolation of a novel
      quinolizidine alkaloid from the methanolic skin extracts of an Ecuadoran frog,
      Epipedobates tricolor. The structure was determined on the basis of MS, IR, and
      NMR analysis as (1R,10R)-1-acetamidoquinolizidine (alkaloid 196). We have named
      this compound epiquinamide, reflecting its origin and structure. The activity of
      the isolated compound was determined in five cell lines expressing various
      nicotinic acetylcholine receptor subtypes. The bioactivity of epiquinamide was
      evaluated on the basis of membrane potential fluorescence and was found to be
      beta2 selective. This compound represents a new structural class of nicotinic
      agonists and a potential lead compound for the development of new therapeutics
      and pharmacological probes for nicotinic receptors. The off-line screening
      technique was found to be very sensitive for the detection of compounds active at
      nicotinic receptors.

PMID- 14575436
TI  - Triterpenoid saponins from the fruits of Ternstroemia japonica.
AB  - Three new triterpenoidal monodesmosides (1-3) and three new triterpenoidal
      bisdesmosides (4-6), together with two known saponins (7 and 8), were isolated
      from the fresh fruits of Ternstroemia japonica. The structures of 1-6
      (ternstroemiasides A-F) were elucidated on the basis of spectral analysis and
      chemical degradation.

PMID- 14575437
TI  - Isolation and structure determination of lyngbyastatin 3, a lyngbyastatin 1
      homologue from the marine cyanobacterium Lyngbya majuscula. Determination of the
      configuration of the 4-amino-2,2-dimethyl-3-oxopentanoic acid unit in
      majusculamide C, dolastatin 12, lyngbyastatin 1, and lyngbyastatin 3 from
      cyanobacteria.
AB  - The structure of lyngbyastatin 3 (1), including the configurations of the two
      unusual amino acid residues, viz., the 3-amino-2-methylhexanoic acid (Amha) and 4
      amino-2,2-dimethyl-3-oxopentanoic acid units (Ibu), has been established by
      chemical degradation. Analysis of the cyanobacterial samples of lyngbyastatin 3
      (1), lyngbyastatin 1 (2), and dolastatin 12 (3) demonstrated that they are
      mixtures of Ibu epimers [R (major) and S (minor)], whereas the structurally
      related majusculamide C (4) is a single diastereomer having an S-Ibu unit.

PMID- 14575439
TI  - Two new epimeric pairs of acetogenins bearing a carbonyl group from Annona
      cherimolia seeds.
AB  - Further studies on the seeds of Annona cherimolia have led to the isolation of
      two pairs of Annonaceous acetogenins, a mixture of epimers of annomolon A (1) and
      34-epi-annomolon A (1'), and a mixture of epimers of annomolon B (2) and 34-epi
      annomolon B (2'), containing a rare gamma-hydroxymethyl-gamma-lactone moiety and
      a carbonyl group. Their structures were elucidated on the basis of spectroscopic
      and chemical methods, and their absolute stereochemistry was solved by preparing
      their respective per-Mosher ester derivatives. These acetogenins showed
      substantial cytotoxicity, comparable to that of adriamycin, against a human
      pancreatic tumor cell line (MIA PaCa-2).

PMID- 14575438
TI  - Semiplenamides A-G, fatty acid amides from a Papua New Guinea collection of the
      marine cyanobacterium Lyngbya semiplena.
AB  - Semiplenamides A (1) to G (7), a series of new anandamide-like fatty acid amides,
      were isolated from a 1997 Papua New Guinea collection of the marine
      cyanobacterium Lyngbya semiplena. The planar structures of these lipids were
      determined using standard 1D and 2D NMR methods. The relative stereochemistry of
      the aliphatic portion of the new metabolites was deduced from 1D NOE data and
      (1)H-decoupling experiments, while the absolute stereochemistry of the amino
      alcohol moieties was assigned by chemical derivatization and chiral GC-MS
      methods. All of these new metabolites displayed toxicity in the brine shrimp
      model system, while semiplenamides A, B, and G showed weak affinity for the rat
      cannabinoid CB(1) receptor and semiplenamide A was a moderate inhibitor (IC(50) =
      18.1 muM) of the anandamide membrane transporter (AMT).

PMID- 14575440
TI  - Komodoquinone A, a novel neuritogenic anthracycline, from marine Streptomyces sp.
      KS3.
AB  - A novel anthracycline, komodoquinone A (1), and its aglycone, komodoquinone B
      (2), were isolated from the solid-state fermentation of the marine Streptomyces
      sp. KS3, which was isolated from marine sediment. The absolute stereostructures
      of 1 and 2, except for the sugar portion, were elucidated on the basis of
      chemical and physicochemical evidence. Komodoquinone A (1) is a unique
      anthracycline, in which a new amino sugar is connected to the D-ring of the
      anthracyclinone skeleton, and was found to induce neuronal cell differentiation
      in the neuroblastoma cell line, Neuro 2A.

PMID- 14575441
TI  - Cassane diterpenoids of Caesalpinia pulcherrima.
AB  - Five new cassane diterpenoids (1-5) were isolated from the roots of Caesalpinia
      pulcherrima, along with the known isovouacapenol C (6), pulcherrimin A (11), and
      6beta-cinnamoyl-7beta-hydroxyvouacapen-5alpha-ol (12). Compounds 3-5 possess the
      alpha,beta-butenolide moiety, whereas compounds 1 and 2 contain a more usual 2,3
      disubstituted furan unit. Compounds 7 and 8 were derived from hydrolysis of 6,
      while 9 and 10 were derived from acetylation and oxidation of 6, respectively.
      The (1)H and (13)C NMR spectra of all compounds were completely assigned using a
      combination of 2D NMR experiments, including (1)H-(1)H COSY, HSQC, HMBC, and T
      ROESY sequences.

PMID- 14575442
TI  - An efficient stereoselective synthesis of cytotoxic 8-epipuupehedione.
AB  - An efficient and highly stereoselective synthesis of cytotoxic 8-epipuupehedione
      (1b) was achieved starting from natural (-)-drimenol (6). The key step to obtain
      stereoselectivity was the simultaneous demethylation and oxidation of the
      dihydrobenzopyran methoxy derivatives 10a and 10b.

PMID- 14575443
TI  - New antioxidant C-glucosylxanthones from the stems of Arrabidaea samydoides.
AB  - Three new C-glucosylxanthones, 2-(2'-O-trans-caffeoyl)-C-beta-d-glucopyranosyl
      1,3,6,7-tetrahydroxyxanthone (1), 2-(2'-O-trans-cinnamoyl)-C-beta-d
      glucopyranosyl-1,3,6,7-tetrahydroxyxanthone (2), and 2-(2'-O-trans-coumaroyl)-C
      beta-d-glucopyranosyl-1,3,6,7-tetrahydroxyxanthone (3), were isolated from the
      stems of Arrabidaea samydoides, in addition to three known C-glucosylxanthones,
      mangiferin (4), 2-(2'-O-benzoyl)-C-beta-d-glucopyranosyl-1,3,6,7
      tetrahydroxyxanthone (5), and muraxanthone (6). Their chemical structures were
      assigned on the basis of MS and 1D and 2D NMR experiments. Xanthones 1-6 showed
      moderate free radical scavenging activity against 1,1-diphenyl-2-picrylhydrazyl
      (DPPH) as well as antioxidant activity evidenced by redox properties measured on
      ElCD-HPLC.

PMID- 14575445
TI  - Cytotoxic constituents of Isodon rubescens var. lushiensis.
AB  - Five new ent-kaurane diterpenoids, ludongnins F-J (1-5), along with 10 known
      compounds, guidongnins A-C (6-8), angustifolin (9), 6-epiangustifolin (10),
      sculponeatin J (11), gardenin D, 5,3',4'-trihydroxy-6,7,8-trimethoxyflavone,
      pedalitin, and quercetin, were isolated from the leaves of Isodon rubescens var.
      lushiensis. The structures of 1-5 were determined by spectroscopic analysis, as
      well as X-ray crystallographic analysis of 1. Compounds 1-11 were evaluated
      against K562 leukemia cells for their cytotoxic effects.

PMID- 14575444
TI  - Lactones from the leaves of Litsea japonica and their anti-complement activity.
AB  - Two new lactones, litsealactone A (1) and litsealactone B (2), were isolated from
      the leaves of Litsea japonica, together with three known lactones,
      hamabiwalactone A (3), hamabiwalactone B (4), and akolactone B (5).
      Hamabiwalactone B (4) and akolactone B (5) significantly inhibited complement
      activity in an in vitro anti-complement assay, with IC(50) values of 149 and 58
      muM, respectively.

PMID- 14575446
TI  - New non-glycosidic diterpenes from the leaves of Stevia rebaudiana.
AB  - Six new labdane-type, non-glycosidic diterpenes, sterebins I-N (1-6), were
      isolated from the leaves of Stevia rebaudiana. Their structures, analogous to
      those of the previously described sterebins A-H, were elucidated on the basis of
      spectroscopic and chemical studies.

PMID- 14575447
TI  - Placidenes C-F, novel alpha-pyrone propionates from the Mediterranean sacoglossan
      Placida dendritica.
AB  - Four new alpha-pyrone-containing propionates (5-8) and an unprecedented
      hydroperoxide 9 have been isolated from the mantle extract of Placida dendritica,
      a Mediterranean sacoglossan that lives upon the green alga Bryopsis plumosa. The
      new metabolites co-occur with the related compounds 1-4, which have been
      described in previous studies of the mollusc. The presence of 9 opens intriguing
      perspectives on the ecological role of placidenes. This paper reports the
      isolation and structural elucidation of the new compounds 5-9.

PMID- 14575448
TI  - Lilacinone, a red aminobenzoquinone pigment from Lactarius lilacinus.
AB  - A red pigment, lilacinone (1), was isolated from fruit bodies of the toadstool
      Lactarius lilacinus. Its structure was established by 2D NMR and APCIMS methods.
      Compound 1 is a novel type of fungal aminobenzoquinone pigment and may be
      biosynthetically derived from three molecules of anthranilic acid.

PMID- 14575451
TI  - Novel crystal structure, cis-trans isomerization, and host property of meta
      substituted macrocyclic azobenzenes with the shortest linkers.
AB  - Azobenzenophanes, in which two (2), three (3), and four (4) azobenzene units are
      connected cyclically by methylene linkers at the meta positions, were
      synthesized. The effect of ring strain on the structure and the photochemical and
      the thermal isomerization of azobenzene were investigated. Complex formation with
      guest species such as alkali metal cations and solvent molecules was observed. X
      ray crystal analyses revealed the crystal structure of all three isomers of 2.
      Compound 2(t,c) was distorted due to the ring strain and 2(c,c) was not deformed.
      Both 3 and 4 formed supramolecular channel structures in which an azobenzenophane
      molecule holds a solvent molecule in the molecular cavity. Upon exposure to
      light, 2, 3, and 4 exhibited stepwise trans-cis photoisomerization in solutions.
      The quantum yields for all isomerization steps of 2 were determined, and these
      values suggested that interactions between chromophores such as energy transfer
      and/or steric distortion affect the isomerization process. The lifetime of 2(c,c)
      (19.7 days) was longer than that of 2(t,c) (6.1 days) at room temperature. The
      relative stability of these isomers was explained by the isokinetic (or
      compensation) relationship between deltaH++ and deltaS++ values and by the effect
      of the ring strain. The relative energies of three isomers of 2 were estimated by
      HF/6-31G** calculations, and these values indicated that 2(t,c) has the largest
      ring strain. Complexes (1:1 and 2:1) between macrocycles and alkali metal cations
      (Li+, Na+, K+, Rb+, Cs+) were observed by ESIMS. The cation selectivity was
      shifted upon photoirradiation especially in 4.

PMID- 14575452
TI  - Synthesis and properties of novel oligothiophenes surrounded by
      bicyclo[2.2.2]octene frameworks.
AB  - Novel oligothiophenes surrounded by bicyclo[2.2.2]octene (abbreviated as BCO)
      frameworks ranging from dimer to hexamer, 1(nT) (n = 2, 3, 4, 6), were prepared,
      and their structures and electronic properties were investigated. Dimer 1(2T) was
      synthesized by oxidative coupling of the 2-lithiated monomer generated from 4,5
      BCO-annelated 2-bromothiophene 8 with CuCl2 in 76% yield. Trimer 1(3T) and
      tetramer 1(4T) were synthesized by Stille coupling of 2,5-dibromo-3,4-BCO
      annelated thiophene 4 and of the 5,5'-dibromo derivative of bis(3,4-BCO-thiophen
      2-yl) 10 with 2-stannylated 4,5-BCO-annelated thiophene 9 in 41% and 46% yield,
      respectively. Hexamer 1(6T) was synthesized by oxidative coupling of terthiophene
      12, tris-annelated with BCO units, in 81% yield. X-ray crystallographic studies
      showed that the thiophene rings in 1(2T) and 1(3T) are rotated around the inter
      ring C-C bond(s) with the C=C-C=C dihedral angles of -174.3(5) degrees for 1(2T)
      and -149.7(3) degrees and 34.4(3) degrees for 1(3T). In the crystal structures of
      1(2T) and 1(3T), no pi-stacking was observed as expected from the steric effect
      of the BCO units. Theoretical calculations for 1(2T) and 1(3T) at the B3LYP/6
      31G(d) level indicated that the annelation with BCO units either at the 2,3- or
      3,4-positions of thiophene rings raises both the KS HOMO and LUMO levels. In the
      electronic absorption spectra of 1, the longest wavelength absorption band
      corresponding to the pi-pi transition is bathochromically shifted with the
      increase in absorption intensity as the number of thiophene rings increases, and
      the absorption of the polythiophene 1 with infinite length was predicted to be
      419 nm. The cyclic voltammetry of 1 in CH2Cl2 at -78 degrees C (2T) or at room
      temperature (3T, 4T, 6T) showed two reversible oxidation waves, indicating that
      the radical cation and dication of 1 are stable under these conditions.

PMID- 14575453
TI  - Chiral recognition of peptide enantiomers by cinchona alkaloid derived chiral
      selectors: mechanistic investigations by liquid chromatography, NMR spectroscopy,
      and molecular modeling.
AB  - The chiral recognition mechanism of a cinchona alkaloid based chiral selector for
      N-protected peptide enantiomers was investigated. A chiral stationary phase
      derived from this selector was employed for liquid chromatographic enantiomer
      separations. It showed exceptionally high enantiomer discrimination for the (all
      R)- and (all-S)-enantiomers of dialanine (alpha = 20), while a pronounced loss of
      chiral recognition occurred upon the insertion of an additional alanine residue
      into the peptide backbone. This reduction of enantioselectivity was investigated
      in great detail by NMR spectroscopy of complexes of the chiral selector and the
      analyte enantiomers accompanied by molecular modeling studies. Investigation of
      intramolecular NOEs provided the conformational states of the free and complexed
      forms of the selector. The analysis of complexation-induced shifts yielded
      information on intermolecular interactions and allowed us to propose binding
      models, which were further supported by the observation of intermolecular NOEs,
      indicating the relative arrangements of selector and analytes. Stochastic
      molecular dynamics simulations were able to reproduce the chromatographic
      retention orders and energy differences, as well as the intermolecular NOEs. The
      computational data were used to evaluate the intermolecular forces responsible
      for analyte binding. In addition, the relative contributions of the fragments of
      the chiral selector to the enantioselective binding event were assessed. A
      spatial arrangement of the chiral selector and the analyte allowing the primary
      ionic interaction as well as hydrogen bonding and pi-pi-stacking to take place
      simultaneously was found to be essential to obtain very high
      enantioselectivities.

PMID- 14575454
TI  - Template-mediated synthesis of lariat RNA and DNA.
AB  - Nucleic acid "lariats" have been of great interest to the biological community
      since their discovery two decades ago as splicing intermediates in the
      biosynthesis of messenger RNA (lariat RNA introns). We report here the first
      synthesis of lariat DNA and RNA via template-mediated chemical ligation of Y
      shaped oligonucleotides. The method allows for the synthesis of lariat DNA of any
      base composition as well as the more biologically relevant lariat RNA. Typically,
      branched precursors and complementary linear templates ("splints") were dissolved
      in an equimolar ratio at a total concentration of 10(-4) M, and ligation was
      promoted by addition of cyanogen bromide in a pH 7.6 buffer. The template
      directed cyclization was very efficient, since the amount of circularized lariat
      product observed in all cases was in the 40-60% range. The lariats were purified
      by polyacrylamide gel electrophoresis, and their structure and nucleotide
      composition confirmed by MALDI-TOF mass spectrometry. Thermal denaturation and
      circular dichroism studies of lariat:RNA and lariat:DNA duplexes were fully
      supportive of the isolated "lasso" structures. Further characterization was
      conducted by enzymatic degradation with spleen phosphodiesterase (a 3'
      exonuclease) and the RNA lariat debranching enzyme, a specific 2',5'
      phosphodiesterase.

PMID- 14575455
TI  - Theoretical study of the ruthenium-catalyzed cyclocotrimerization of alkynes with
      isocyanates and iothiocyanates: cemoselective formation of pyridine-2-one and
      thiopyrane-2-imine.
AB  - The cyclocotrimerization of acetylene with isocyanate HNCO and isothiocyanate
      HNCS, mediated by CpRuCl, is theoretically investigated on the basis of DFT/B3LYP
      calculations. By these means, the experimental result can be rationalized as to
      why, with HNCO, a nitrogen-heterocycle is formed, but with HNCS a sulfur
      heterocycle is formed. According to the proposed mechanism, the key reaction step
      is the addition of a double bond to a metallacyclopentatriene formed by oxidative
      coupling of two acetylene ligands coordinated to CpRuCl, giving a bicyclic
      carbene intermediate. This double-bond-addition is initiated by eta1 attack at
      the ruthenium center, and it is just the attacking atom that is going to be
      incorporated into the cycle. Thus, the chemoselectivity originates from the fact
      that, for HNCO, N attack is preferred over O, but for HNCS, S attack is preferred
      over N. The onward reaction is a reductive elimination to give a coordinatively
      unsaturated metallaheteronorbornene intermediate finally rearranging to a ligated
      heterocycle. Completion of the cycles is achieved by an exothermic displacement
      of the respective heterocyclic product by two acetylene molecules which
      regenerates the bisacetylene complex.

PMID- 14575456
TI  - Supramolecular self-assemblies of beta-cyclodextrins with aromatic tethers:
      factors governing the helical columnar versus linear channel superstructures.
AB  - A series of 6-O-(p-substituted phenyl)-modified beta-cyclodextrin derivatives,
      i.e., 6-O-(4-bromophenyl)-beta-CD (1), 6-O-(4-nitrophenyl)-beta-CD (2), 6-O-(4
      formylphenyl)-beta-CD (3), 6-phenylselenyl-6-deoxy-beta-CD (4), and 6-O-(4
      hydroxybenzoyl)-beta-CD (5), were synthesized, and their inclusion complexation
      behavior in aqueous solution and self-assembling behavior in the solid state were
      comparatively studied by NMR spectroscopy, microcalorimetry, crystallography, and
      scanning tunneling microscopy. Interestingly, (seleno)ethers 1-4 and ester 5
      displayed distinctly different self-assembling behavior in the solid state,
      affording a successively threading head-to-tail polymeric helical structure for
      the (seleno)ethers or a mutually penetrating tail-to-tail dimeric columnar
      channel structure for the ester. Combining the present and previous structures
      reported for the relevant beta-CD derivatives, we further deduce that the pivot
      heteroatom, through which the aromatic substituent is tethered to beta-CD, plays
      a critical role in determining the helix structure, endowing the 2-fold and 4
      fold axes to the N/O- and S/Se-pivoted beta-CD aggregates, respectively. This
      means that one can control the self-assembling orientation, alignment, and
      helicity in the solid state by finely tuning the pivot atom and the tether
      length. Further NMR and calorimetric studies on the self-assembling behavior in
      aqueous solution revealed that the dimerization step is the key to the formation
      of linear polymeric supramolecular architecture, which is driven by favorable
      entropic contributions.

PMID- 14575457
TI  - Hydroesterification reactions with palladium-complexed PAMAM dendrimers
      immobilized on silica.
AB  - Highly active, recyclable catalytic systems for the hydroesterification reaction
      of olefins with methanol and carbon monoxide were prepared by complexing various
      palladium species to generation zero through four PAMAM dendrimers immobilized on
      silica. The silica-dendrimer-Pd(PPh2)2 complexes were the most facile recyclable
      catalysts and could be recycled four to six times by filtration under air. These
      catalysts show selectivity for the linear reaction product.

PMID- 14575458
TI  - Toward the development of new photolabile protecting groups that can rapidly
      release bioactive compounds upon photolysis with visible light.
AB  - The synthesis and characterization of a new photolabile protecting group (caging
      group) for carboxylic acids, the 2-(dimethylamino)-5-nitrophenyl (DANP) group, is
      described. This compound has a major absorption band in the visible wavelength
      region with a maximum near 400 nm (epsilon400 = 9077 M(-1) cm(-1) at pH 7.4 and
      21 degrees C). The caging group is attached through an ester linkage to the
      carboxyl functionality of beta-alanine, which activates the inhibitory glycine
      receptor in the mammalian central nervous system. Such caged compounds play an
      important role in transient kinetic investigations of fast cellular processes.
      Upon photolysis of DANP-caged beta-alanine, the caging group is released within 5
      micros. Quantum yields of 0.03 and 0.002 were obtained in the UV region (308 and
      360 nm) and the visible region (450 nm), respectively. Laser-pulse photolysis
      experiments, using 337 or 360 nm light, were performed with the caged compound
      equilibrated with HEK 293 cells transiently transfected with cDNA encoding the
      alpha1 homomeric, wild-type glycine receptor. The experiments demonstrated that
      neither DANP-caged beta-alanine nor its byproducts inhibit or activate the
      glycine receptors on the cell surface. Under physiological conditions, the DANP
      caged beta-alanine is water-soluble and stable and can be used for transient
      kinetic measurements.

PMID- 14575459
TI  - Synthesis, crystal structures, and laser flash photolysis of tert-butyl
      aroylperbenzoates.
AB  - tert-Butyl aroylperbenzoates (1-7) were synthesized. Single-crystal structures
      for 2 and 5 show that the perester and benzophenone carbonyl groups are almost
      coplanar in each. Laser flash photolysis (LFP, lambdaex = 355 nm) of 1-5 in CCl4
      produces the corresponding aroylphenyl radicals (9-13). The lifetimes of the para
      aroyl-substituted phenyl radicals (9-12) are similar (approximately 0.4 micros),
      but each is shorter lived than the meta aroyl-substituted phenyl radical (13).
      LFP of 2, 6, and 7 also produces different (tert-butyldioxycarbonylbenzoyl)benzyl
      radicals (8, 14, and 15, lambdamax approximately 320 nm). The lifetimes of each
      in CCl4 have been found to be approximately 17-18 micros. The effect of
      substituents on the quantum yield of decomposition of 1-7 and the lifetimes of 9
      13 is discussed.

PMID- 14575460
TI  - Naphtho[1,2-c:5,6-c]difuran: a reactive linker and cyclophane precursor.
AB  - Naphtho[1,2-c:5,6-c]difuran has been isolated in a 9-step synthesis from 2,6
      dimethylnaphthalene. It is a highly reactive diene similar in nature to the
      related isobenzofuran. In Diels-Alder reactions, its intermediate monoadducts are
      actually less reactive that the parent difuran making possible sequential Diels
      Alder reactions with different dienophiles. Reaction with a tethered
      bis(dienophile) leads to the production of a naphthalenic cyclophane.

PMID- 14575461
TI  - Synthesis, electrochemistry and self-assembled monolayers of novel
      tetrathiafulvalene (TTF) and pi-extended TTF (exTTF) disulfides.
AB  - The synthesis of a new series of tetrathiafulvalene (TTF) and pi-extended TTF
      (exTTF) disulfides and the electrochemical properties of self-assembled
      monolayers derived from these compounds are described. When the intermediate
      bromides 3 and 7 were reacted with thiourea, followed by basic hydrolysis, the
      expected thiol formation was not observed and only disulfides were obtained. A
      mechanism is proposed to explain the self-oxidation process of these compounds.
      For the first time SAMs of exTTF derivatives were prepared. Electrochemical data
      for SAMs of 6 and 8 reveal a single two-electron chemically reversible oxidation
      process to form a dicationic state, typical of the exTTF system. The SAMs are
      stable over extended periods of time and show electrochemical stability upon
      repeated potential scans.

PMID- 14575462
TI  - Radical carbonylation/reductive cyclization for the construction of
      tetrahydrofuran-3-ones and pyrrolidin-3-ones.
AB  - Beta-hydroxyalkyl aryl chalcogenides obtained by regioselective ring-opening of
      epoxides with benzeneselenolate or -tellurolate were found to undergo efficient
      hetero-Michael addition when treated with ethyl propiolate. Subsequent
      carbonylation/reductive cyclization of the resulting vinylogous carbonates in the
      presence of AIBN/TTMSS and carbon monoxide (80 atm) afforded 2,5-disubstituted
      tetrahydrofuran-3-ones, predominantly as cis isomers (cis/trans = 4/1-9/1).
      Starting from a polymer-supported diaryl diselenide, the methodology was also
      successfully extended to solid-phase synthesis. Vinylogous carbamates prepared by
      hetero-Michael addition of aziridines to electron-deficient alkynes were
      regioselectively ring-opened with benzeneselenolate from the sterically least
      hindered side. Radical carbonylation/reductive cyclization of the resulting N
      vinyl-beta-amino-alkyl phenyl selenides afforded 2,5-disubstituted pyrrolidin-3
      ones, predominantly as cis isomers (cis/trans = 3/1-12/1).

PMID- 14575463
TI  - m-Phenylene ethynylene sequences joined by imine linkages: dynamic covalent
      oligomers.
AB  - Imine metathesis between m-phenylene ethynylene oligomers of various lengths was
      performed in acetonitrile, a solvent in which oligomers containing eight or more
      repeat units adopt a compact helical conformation. The equilibrium constants and
      corresponding free energy change for the imine metathesis reactions were
      estimated. The results showed that the magnitude of equilibrium shifting measured
      by the free energy change for the formation of imine-containing oligomers
      increases linearly below a critical product chain length and grows asymptotically
      above it. The linear region is ascribed to the constant increase in contact area
      between monomer units of adjacent helical turns as the product chain grows to the
      12-mer. Once the ligation product is 12 units in length, full contact is made
      between adjacent helical turns. On the other hand, for imine metathesis between
      oligomers leading to products having more than 12 units, the driving force is the
      difference between the folding energy of products and that of reactants. The
      additional stabilizing energy is roughly constant, regardless of the chain
      length, since the contact area between adjacent helical turns is unchanged.
      Consistent with the notion that the imine bond only minimally destabilizes the
      helical conformation, the position of the imine bond in the ligation product has
      been observed to have no significant effect on the folding stability. The
      magnitudes of equilibrium shifting are similar for ligation products of the same
      length but having the imine at various positions along the sequence. This
      suggests that the imine bond is compatible with the m-phenylene ethynylene
      backbone, regardless of the position in the sequence. Imine metathesis of m
      phenylene ethynylene oligomers could allow a quick access to an unbiased, dynamic
      library of oligomer sequences joined by imine linkages.

PMID- 14575464
TI  - N,N-dichloro-2-nitrobenzenesulfonamide as the electrophilic nitrogen source for
      direct diamination of enones.
AB  - N,N-dichloro-o-nitrobenzenesulfonamide (2-NsNCl2) was found to be an effective
      electrophilic nitrogen source for the direct diamination of alpha,beta
      unsaturated ketones without the use of any metal catalysts. The reaction is very
      convenient to carry out without the protection of inert gases. Molecular sieves
      (4 A) and temperature were found to play key roles in controlling the formations
      of 3-trichloromethyl and dichloromethyl imidazoline products (16 examples). The 2
      Ns-protection group of the resulting diamine products can be easily cleaved under
      mild Fukuyama's conditions. A new mechanism hypothesis of [2+3] cyclization and N
      chlorination has been proposed to explain the product structures, particularly
      their regio- and stereochemistry.

PMID- 14575465
TI  - N-functionalization of poly(ethylene glycol)-linked mono- and bis-dioxocyclams as
      potential ligands for Gd3+.
AB  - A number of highly functionalized dioxocyclams with acetic acid side chains on
      the secondary amine sites and ethylene glycol side chains on 6 and 13-positions
      (12a, 12b) or a tetra(ethylene glycol) side chain linking the 6 and 13 positions
      (15) were synthesized and characterized, as was a bis-dioxocyclam bridged across
      the 6 and 13 positions by tetra(ethylene glycol) groups (16). These were screened
      for their ability to complex Gd3+. Only ligands 15 and 16, having tetra(ethylene
      glycol) groups, formed such complexes.

PMID- 14575466
TI  - Application of a new bicyclic triaminophosphine ligand in Pd-catalyzed Buchwald
      Hartwig amination reactions of aryl chlorides, bromides, and iodides.
AB  - The new bicyclic triaminophosphine ligand P(i-BuNCH2)3CMe (3) has been
      synthesized in three steps from commercially available materials and its efficacy
      in palladium-catalyzed reactions of aryl halides with an array of amines has been
      demonstrated. Electron-poor, electron-neutral, and electron-rich aryl bromides,
      chlorides, and iodides participated in the process. The reactions encompassed
      aromatic amines (primary or secondary) and secondary amines (cyclic or acyclic).
      It has also been shown that the weak base Cs2CO3 can be employed with ligand 3,
      allowing a variety of functionalized substrates (e.g., those containing esters
      and nitro groups) to be utilized in our amination protocols. This ligand provides
      a remarkably general, efficient, and mild palladium catalyst for aryl iodide
      amination. Although 3 is slightly air and moisture sensitive, easy procedures can
      be adopted that avoid the need of a glovebox. Comparisons of the efficacy of 3 in
      these reactions with that of the proazaphosphatrane P(i-BuNCH2CH2)3N (2) reveal
      that in addition to the opportunity for transannulation in 2 (but not in 3),
      other significant stereoelectronic contrasts exist between these two ligands
      which help account for differences in the activities of the Pd/2 and Pd/3
      catalytic systems.

PMID- 14575467
TI  - Synthesis of the first stable phosphonamide transition state analogue.
AB  - Three methods were selected for the one-pot synthesis of the fully protected beta
      fluoroaminophosphonic acids, using the readily accessible N-protected beta
      fluoroaminals. These were activated by acylation leading, by beta-elimination, to
      a transient N-acylimine immediately trapped by reactive forms of dialkyl
      phosphites. Avoiding basic conditions, the complete or partial deprotection of
      these N-protected beta-fluoroaminophosphonic esters allowed the synthesis of the
      free amino acids, their esters, and a racemic beta-trifluorophosphonamidic acid.
      The latter, which represents a transition state analogue formed by the bacterial
      transpeptidase, is perfectly stable at pH 4.7, contrary to the nonfluorinated
      compounds.

PMID- 14575468
TI  - Heterodimerization of olefins. 1. Hydrovinylation reactions of olefins that are
      amenable to asymmetric catalysis.
AB  - Through a systematic examination of ligand and counterion effects, new protocols
      for a nearly quantitative and highly selective codimerization of ethylene and
      various functionalized vinylarenes have been discovered. In a typical reaction, 4
      bromostyrene and ethylene undergo codimerization in the presence of 0.0035 equiv
      each of [(allyl)NiBr]2, triphenylphosphine, and AgOTf in CH2Cl2 at -56 degrees C
      to give 3-(4-bromophenyl)-1-butene in >98% yield and selectivity. Corresponding
      reactions with [(allyl)PdX]2 are much less efficient and less selective and may
      require further optimization before a viable system can be identified. Another
      useful protocol that gives comparable yield and selectivity involves the use of a
      single-component catalyst prepared from allyl 2-diphenylphosphinobenzoate,
      Ni(COD)2, and (C6F5)3B. Recognition of a synergistic relationship between a
      chiral hemilabile ligand (for example, (R)-2-methoxy-2'-diphenylphosphino-1,1'
      binaphthyl, MOP) and a highly dissociated counteranion (BARF or SbF6) in an
      enantioselective version of the Ni-catalyzed reaction raises the prospects of
      developing a practical route for the synthesis of 3-arylbutenes. Several
      pharmaceutically relevant compounds, including widely used 2-arylpropionic acids,
      can be synthesized from these key intermediates. This reaction appears to be
      quite general. Synthesis of several new 2-diphenylphosphino-1,1-binaphthyl
      derivatives, prepared to probe the effect of hemilabile coordination on the
      efficiency and selectivity of the reaction, are also described.

PMID- 14575469
TI  - Synthesis of [ethylene-1-(eta(5)-4,5,6,7-tetrahydro-1-indenyl)-2- (eta(5)
      4',5',6',7'-tetrahydro-2'-indenyl)]titanium dichloride, the elusive isomer of the
      Brintzinger-type ansa-titanocenes.
AB  - We present a short synthesis of 1-(2-indenyl)-2-(3-indenyl)ethane (5) and a
      method for its conversion to the ansa-metallocene [ethylene(eta5-inden-1-yl)(eta5
      inden-2-yl)]titanium dichloride (13). The synthetic strategy applied to prepare
      bisindene 5 relies on the efficient alkylation of 2-(phenylsulfonyl)indane
      followed by HMPA-assisted E1cB-elimination of phenylsulfinate. This tandem
      sequence circumvents the predisposition of indene to undergo C(1)-alkylation and
      enables access to C(2)-substituted indenes. The key step in the synthesis of the
      title ansa-titanocene (4) features a previously unreported equilibration step to
      generate the bis(indenide anion) of 5. Complexation with TiCl4.(THF)2 followed by
      hydrogenation of the product metallocene furnishes ansa-titanocene 4.

PMID- 14575470
TI  - The 3,4-O-carbonate protecting group as a beta-directing group in
      rhamnopyranosylation in both homogeneous and heterogeneous glycosylations as
      compared to the chameleon-like 2,3-O-carbonates.
AB  - It is demonstrated that the beta-selectivity observed in the insoluble silver
      salt mediated couplings of 2,3-O-carbonate-protected rhamnosyl bromides is
      uniquely due to the heterogeneous nature of the reaction. In homogeneous solution
      these same donors are alpha-selective, a fact that is attributed to the half
      chair conformation of these substances which reduces the energy barrier to
      oxacarbenium ion formation. It is suggested that the 2,3-O-carbonate group be
      dubbed torsionally arming in the manno- and rhamnopyranose series. When the
      carbonate group is removed to the 3,4-O-position a beta-selective system is
      formed, in both homogeneous and heterogeneous conditions, and it is demonstrated
      that this selectivity arises from the combination of the electron-withdrawing
      nature of the carbonate and its inability to take part in neighboring
      participation.

PMID- 14575471
TI  - Identification of novel macrocyclic peptidase substrates via on-bead enzymatic
      cyclization.
AB  - Peptidase-catalyzed formation of macrocyclic lactams on solid phase identifies
      ring systems that are favorably bound in the enzyme active site. We evaluated
      several cyclic peptide motifs linked by ester bonds between the P2 and P1' or the
      P1 and P2' side chains. The depsipeptide represented by structure 5 was readily
      generated by a variety of peptidases from precursor omega-amino acids or omega
      amino esters. This strategy for identifying ring systems for potential
      macrocyclic transition state analogues was demonstrated with the serine
      peptidases trypsin and chymotrypsin, with the aspartic peptidase pepsin, and with
      the zinc peptidase thermolysin.

PMID- 14575472
TI  - Synthesis and evaluation of macrocyclic transition state analogue inhibitors for
      alpha-chymotrypsin.
AB  - Lactams 1 and 2 are readily formed from acyclic precursors in the presence of
      trypsin and chymotrypsin, respectively, identifying the macrocyclic ring system
      as a potential motif for constrained transition state analogue inhibitors of the
      serine peptidases. Ketone 3 was synthesized and shown to be a modest inhibitor of
      chymotrypsin (Ki = 220 microM), albeit 4-fold more potent than the acyclic
      hydroxy acid 25 (Ki = 1.5 mM as a mixture of epimers). A precursor (31) to the
      amino boronic acid 4 was also prepared; although this derivative was a potent
      inhibitor of chymotrypsin (Ki = 130 nM) by virtue of the boronic acid moiety, it
      showed no advantage over the des-amino analogue 32 (Ki = 120 nM), which is not
      capable of cyclizing.

PMID- 14575473
TI  - Synthesis and cycloaromatization of a cyclic enyne-allene prodrug.
AB  - A simple and stable cyclic enediynone (4) has been synthesized using an
      intramolecular Nozaki-Hiyama-Kishi cyclization as the key step. Reaction with a
      thiolate nucleophile led to rapid cycloaromatization of 4. Trapping experiments
      using 1,4-cyclohexadiene support the intermediacy of an aromatic diradical in the
      cycloaromatization.

PMID- 14575474
TI  - Modeling and experiment reveal an unexpected stereoelectronic effect on
      conformation and scalar couplings of alpha-aminoorganostannanes, with possible
      relevance to the tin-lithium exchange reaction.
AB  - The solution conformation of N-methyl-2-(tributylstannyl)piperidines has been
      determined through the use of vicinal 119Sn-13C coupling constants, revealing a
      conformational distortion caused by an unexpected stereoelectronic effect in some
      cases. Specifically, the "equatorial" conformer is distorted into a half-chair,
      in which the nitrogen lone pair eclipses the C-Sn bond. This distortion, which
      "costs" approximately 1 kcal/mol, correlates with a conformational dependence of
      geminal 119Sn-15N couplings and a possible correlation with reactivity in the tin
      lithium exchange reaction.

PMID- 14575476
TI  - Conformational studies by dynamic NMR. 95. Rotation around the adamantyl-alkyl
      bond. Remote substituent effect on conformational equilibrium.
AB  - Restricted rotation has been observed by NMR spectroscopy at very low temperature
      in isopropyladamantane, 1-tert-butyl-3-isopropyladamantane, and 1,3
      diisopropyladamantane. The barriers for the corresponding dynamic processes were
      also determined. In the case of the disubstituted adamantane derivatives, two and
      four conformers, respectively, were observed and they were assigned on the basis
      of the symmetry properties. The relative populations deviate from the statistical
      distribution.

PMID- 14575475
TI  - Chemically defined sialoside scaffolds for investigation of multivalent
      interactions with sialic acid binding proteins.
AB  - Four glycodendrons and a glycocluster were synthesized from carbohydrate building
      blocks to form paucivalent (di- to tetravalent) structures of controlled scaffold
      architectures. Enzymatic sialylation of the functionalized cluster and dendrons,
      terminated in lactose residues, generated a library of paucivalent synthetic
      sialosides displaying sialic acids with different dispositions. These newly
      constructed bioactive sialic acid-based structures were differentially recognized
      by sialoadhesin, a mammalian macrophage sialic acid binding protein. The binding
      of the sialosides to sialoadhesin was evaluated by an enzyme-linked immunosorbant
      assay to investigate the complementarity of scaffold structure and binding to
      sialoadhesin. Modulating the interaction between sialoadhesin and its sialic acid
      ligands has important implications in immunobiology.

PMID- 14575478
TI  - Ruthenium-catalyzed cyclopropanation of alkenes using propargylic carboxylates as
      precursors of vinylcarbenoids.
AB  - Intermolecular cyclopropanation reactions of various alkenes with propargylic
      carboxylates 1 are catalyzed by [RuCl2(CO)3]2 to give vinylcyclopropanes 2 in
      good yields. The key intermediate of the reaction is a vinylcarbene complex
      generated in situ by nucleophilic attack of a carbonyl oxygen of the carboxylates
      to an internal carbon of the alkyne activated by the ruthenium complex. A variety
      of transition-metal compounds other than the Ru compound can also be employed in
      this system. Similar cyclopropanation proceeds with conjugated dienes as well to
      give trans-vic-divinylcyclopropane derivatives and cycloheptadiene derivatives 5,
      the latter being thermally derived from the initially formed cis-vic-isomers via
      Cope-type rearrangement. The present reaction is chemically equivalent to the
      transition metal-catalyzed cyclopropanation reaction using alpha-diazoketones as
      carbenoid precursors.

PMID- 14575477
TI  - Total synthesis of wedelolactone.
AB  - The total synthesis of wedelolactone, a naturally occurring direct inhibitor of
      IKK complex that can suppress LPS-induced caspase-11 expression, using a
      convergent synthetic approach, is described. The key steps involved in this
      synthesis include the palladium-catalyzed Sonogashira reaction and the palladium
      catalyzed carbonylative annulation reaction. This approach allows access to
      diversified analogues of wedelolactone.

PMID- 14575479
TI  - Reaction and characterization of thioamide dianions derived from N-benzyl
      thioamides.
AB  - Thioamide dianions were generated by the highly efficient reaction of N-benzyl
      thioamides with 2 equiv of BuLi. Alkylation, allylation, and silylation took
      place selectively at the carbon atom adjacent to the nitrogen atom of the
      thioamide dianions. Oxiranes and an aldehyde were also used as electrophiles in
      the reaction of thioamide dianions to form N-thioacyl 1,3- or 1,2-amino alcohols.
      The insertion reaction of elemental sulfur to a thioamide dianion and subsequent
      ethylation afforded a N-thioacyl hemithioaminal. NMR studies on the thioamide
      mono- and dianions derived from N-benzyl 2-methoxythiobenzamide showed a linear
      relationship between the chemical shifts of all carbon atoms of thioamide mono-
      and dianions. The results also suggested that the negative charge at the benzylic
      carbon atom of the dianion is not fully delocalized. The charge distribution
      patterns of the dianion are consistent with those of pi polarization.

PMID- 14575480
TI  - A kinetic study of 1,3-dipolar cycloadditions in micellar media.
AB  - The kinetics of the 1,3-dipolar cycloadditions (DC) of benzonitrile oxide with a
      series of N-substituted maleimides in micellar media have been investigated.
      Surfactants studied include anionic sodium dodecyl sulfate, cationic
      cetyltrimethylammonium bromide, and a series of nonionic alkyl poly(ethylene
      oxide) surfactants (CxEy). The kinetic data have been analyzed by using the
      pseudo-phase model for bimolecular reactions. Much larger micellar accelerations
      (up to a factor of 17) were observed for these reactions than was previously
      found for Diels-Alder (DA) reactions (J. Org. Chem. 2002, 67, 7369-7377). This is
      explained by the smaller solvent sensitivity of DC reactions, which causes the
      micellar rate constants to be much closer to the value of water (km/kw
      approximately 0.25-0.45 for DC reactions vs 0.02-0.05 for DA reactions). Further
      evidence is presented, that a water/1-propanol mixture ([H2O] ca. 15 M) is a
      fairly good mimic of the micellar reaction environment for these reactions.
      Isobaric activation parameters have been determined for the reaction in the
      micellar phase of C16E20, using micellar rate constants. They correspond well to
      values obtained for the aforementioned micelle mimic.

PMID- 14575481
TI  - Totally stereoselective synthesis of 1,3-disaccharides through Diels-Alder
      reactions.
AB  - A nonclassical, totally stereoselective synthesis of orthogonally protected 1,3
      disaccharides is reported. Enantiomerically pure beta-keto-delta-lactones,
      efficiently obtained from glucal and galactal, are transformed into electron-poor
      heterodienes and chemo-, regio-, and stereoselectively cycloadded to glycals as
      electron-rich dienophiles, to directly afford 2-thiodisaccharides. The reductive
      desulfurization of the latter smoothly gave the corresponding 2,2'
      dideoxydisaccharides.

PMID- 14575482
TI  - Solid-supported synthesis of cryptand-like macrobicyclic peptides.
AB  - A straightforward method for the solid-supported synthesis of cryptand-like
      bicyclic peptides (1-5) on a backbone amide linker has been described. For the
      branching, two novel easily available building blocks, viz. N-(4-methoxytrityl)-N
      (2-nitrobenzenesulfonyl)-protected N,N-bis(2-aminoethyl)-beta-alanine (6) and N
      (9-fluorenylmethoxycarbonyl) protected iminodiacetic acid monoallyl ester (7),
      have been employed. The key steps of the synthesis are as follows: (i) stepwise
      coupling of one amino acid and 6 to the secondary amino group of the linker; (ii)
      removal of the 2-nitrobenzenesulfonyl group and SPPS by the Fmoc chemistry, using
      7 as the penultimate and tert-butoxycarbonyl (Boc) protected glycine as the last
      amino acid; (iii) removal of the 4-methoxytrityl protection and subsequent SPPS
      by the Fmoc chemistry; (iv) removal of the allyl and Fmoc groups, followed by
      cyclization; and (v) removal of the Boc and tert-butyl groups, followed by
      cyclization. Final cleavage from the support and removal of benzyl-derived
      protecting groups gives the desired bicyclic products.

PMID- 14575483
TI  - Functionalizations of [6]- and [7]helicenes at their most sterically hindered
      positions.
AB  - Although the reactions of enol ethers of aryl methyl ketones with benzoquinone
      make it easy to prepare nonracemic helicenes that are substituted by hydroxyl
      groups at their 1,omega-positions, the hydroxyl groups fail to facilitate the
      introduction of electrophiles ortho to them. However, ethers of [6]- and
      [7]helicenols prepared in this way, seemingly because of the activation by the
      alkoxyl groups at the 6-positions, combine with electrophilic reagents to
      introduce bromines and acyl groups exactly into these positions. Moreover, these
      bromine and acyl groups can be transformed into other functional groups
      (including phosphine oxides and acetylenes), the ether functions adjacent to
      these functional groups can then be removed, and the phenols can be oxidized to
      quinone-acetals. An alternative way to introduce functional groups next to the
      phenols is to rearrange their phosphate esters. Two reactions that differentiate
      the ends of the helicenes are also described.

PMID- 14575484
TI  - Polycyclic aromatic compounds via radical cyclizations of benzannulated enyne
      allenes derived from Ireland-Claisen rearrangement.
AB  - A new synthetic sequence involving the use of Ireland-Claisen rearrangement of
      propargylic acetates to form the corresponding benzannulated enyne-allenes
      followed by Schmittel cyclization to generate benzofulvene biradicals for radical
      cyclizations leading to polycyclic aromatic compounds was established. Treatment
      of 9-fluorenone (8) with the lithium acetylide 9 followed by acetic anhydride
      produced the propargylic acetate 10. A sequence of reactions occurred after 10
      was converted to the corresponding silyl ketene acetal 11. An initial Ireland
      Claisen rearrangement produced the benzannulated enyne-allene 12, which then
      underwent a Schmittel cyclization reaction to generate the benzofulvene biradical
      13. A subsequent intramolecular radical-radical coupling then produced the formal
      Diels-Alder adduct 14, which in turn underwent a prototropic rearrangement to
      give the silyl ester 15 and, after hydrolysis, the carboxylic acid 16 in 57%
      overall yield from 10 in a single operation. An intramolecular acylation reaction
      of 16 produced the ketone 17. The carboxylic acids 24-26 were likewise prepared
      from the diaryl ketones 18-20, respectively. However, the intramolecular [2 + 2]
      cycloaddition reaction of the benzannulated enyne-allene 33 having a tert-butyl
      group at the allenic terminus occurred preferentially, producing the 1H
      cyclobut[a]indenyl acetic acid 35 as the predominant product.

PMID- 14575485
TI  - Synthesis of 6-mono-6-deoxy-beta-cyclodextrins substituted with isomeric
      aminobenzoic acids. Structural characterization, conformational preferences, and
      self-inclusion as studied by NMR spectroscopy in aqueous solution and by X-ray
      crystallography in the solid state.
AB  - The synthesis, purification, and characterization of mono-6-modified-beta
      cyclodextrins bearing N-attached o-, m-, and p-aminobenzoic acids (2, 3, and 4,
      respectively) are presented. The structures in aqueous solution were investigated
      using one- and two-dimensional NMR spectroscopy. Detailed assignment of the
      spectra together with intramolecular NOE correlations revealed the way each of
      the isomeric appendages is positioned relative to the macrocyclic cavity. No self
      inclusion is observed. The o-isomer 2 turns inward over the top of the primary
      side and interacts with specific protons of the substituted glucopyranose unit A
      and those of a neighboring unit. The m-isomer 3 displays two conformations, where
      the substituent resides above the primary side in a tilted manner and interacts
      either with the previous or the next unit. We propose that the carboxyl groups in
      both 2 and 3 are localized through H-bonding with one or two, respectively,
      primary hydroxyl groups of the neighboring glucopyranose units. In a similar
      positioning of the aromatic ring of the p-isomer 4, the hydrophilic carboxyl end
      is fully exposed to the aqueous environment. The X-ray structure of 4 shows that
      the solution conformation has evolved such that in the crystalline state, the
      aromatic moiety is inserted through its carboxyl part inside another CD where it
      establishes intermolecular H-bonds with inward-turned primary OH groups. Besides
      this stabilization, 4 forms parallel and antiparallel supramolecular chains in
      the crystal that are additionally stabilized by direct H-bonds.

PMID- 14575486
TI  - Regioselective oxidations of benzocarbaporphyrins with ferric chloride: a facile
      synthesis of bridged [18]annulene ketals with strong absorptions in the far red
      and an unexpected halogenation reaction at the interior carbon atom.
AB  - Benzocarbaporphyrins 4 were found to undergo regioselective oxidations with
      ferric chloride in methanol, ethanol, isopropyl alcohol, or ethylene glycol to
      give bridged benzo[18]annulene ketal derivatives 5 in excellent yields. These
      polar derivatives were generally isolated in a monoprotonated form and the
      corresponding free bases appeared to be relatively unstable. Addition of TFA
      resulted in the formation of spectroscopically distinct dications. The ketals 5
      were highly diatropic in nature, showing the internal alkoxy substituents upfield
      beyond -1 ppm in their proton NMR spectra. The external meso-protons resonated
      near 10 ppm, confirming the presence of a strong aromatic ring current. The UV
      vis spectra for 5 showed a Soret band at 422 nm, and two strong absorptions in
      the far red at 751 and 832 nm. A carbaporphyrin with a fused acenaphthylene ring
      was also oxidized with ferric chloride and this produced a ketal derivative with
      still further bathochromically shifted absorptions particularly for the Soret
      band. Also, the use of different alcohols in these reactions allows the overall
      polarity of these ketal products to be controlled and this could have merit in
      biomedical applications. Reaction of carbaporphyrin 4a with aqueous ferric
      chloride afforded the corresponding 21-chloro derivative 20 in good yields, and
      at longer reaction times a nonaromatic dione was isolated. Aqueous ferric bromide
      gave a 21-bromocarbaporphyrin product but in this case very poor yields (<10%)
      were noted. Mechanisms are proposed to explain the formation of these unusual
      oxidation products. The structure of 21-chlorocarbaporphyrin 20 was further
      demonstrated by X-ray crystallography. The presence of the interior chlorine atom
      was found to tilt the indene moiety by 29.59(4) degrees relative to the
      [18]annulene macrocyclic ring. The crystal packing for 20 shows offset face-to
      face pi-stacking interactions that link the porphyrinoid molecules as closely
      paired dimers.

PMID- 14575487
TI  - Ruthenium-catalyzed cyclocarbonylation of allenyl alcohols and amines: selective
      synthesis of lactones and lactams.
AB  - Allenyl alcohols such as 4-hydroxybuta-1,2-dienes and 5-hydroxypenta-1,2-dienes
      having a variety of substituents undergo cyclocarbonylation in the presence of a
      ruthenium catalyst under mild conditions selectively to give five- and six
      membered lactones in a high yield with 100% atom economy. 5-Aminopenta-1,2-dines
      are also cyclocarbonylated to give gamma-lactams. A possible carbonylation
      mechanism involving a ruthenium cluster intermediate is proposed on the basis of
      experimental results.

PMID- 14575488
TI  - Double diastereoselection in aldol reactions mediated by dicyclohexylchloroborane
      between L-erythrulose derivatives and chiral aldehydes. The Felkin-Anh versus
      Cornforth dichotomy.
AB  - Both matched and mismatched diastereoselections have been observed in aldol
      reactions of the B,B-dicyclohexylboron enolate of a protected l-erythrulose
      derivative with a range of chiral aldehydes. The stereochemical outcome of
      reactions with alpha-methyl aldehydes can be adequately explained within the
      Felkin-Anh paradigm. In the case of alpha-oxygenated aldehydes, however, strict
      adherence to this model does not allow for a satisfactory account of the observed
      results. In such cases, the Cornforth model provides a much better explanation.

PMID- 14575490
TI  - Poly[n]prismanes: a family of stable cage structures with half-planar carbon
      centers.
AB  - A series of bi[n]prismanes and tri[n]prismanes (n = 3-6) containing n and 2n,
      respectively, tetracoordinated carbon centers with nonclassical bisphenoidal
      (half-planar) configuration has been designed computationally.

PMID- 14575489
TI  - An efficient route to pyrimidine nucleoside analogues by [4 + 2] cycloaddition
      reaction.
AB  - We report here an efficient synthesis for pyrimidine nucleoside analogues by [4 +
      2] cycloaddition reaction. These compounds were obtained by convergent chemistry
      from glycosyl isothiocyanates 3a-f (pyranoses, furanoses, and dissaccharides) and
      diazadienium salt 5. In fact, diazapentadienium iodide 5 prepared from
      vinylthioamide 4 is an efficient intermediate in heterocyclic synthesis and
      reacts with isothiocyanates 3a-f affording beta-D-uracil analogues 7a-f in good
      yields and with total regiocontrol. All compounds were fully characterized by IR,
      HRMS, and 13C and 1H NMR (COSY and HMQC).

PMID- 14575491
TI  - Scope of Ru(II)-catalyzed synthesis of pyridines from alkynes and nitriles.
AB  - Pyridines can be efficiently synthesized by Ru(II)-catalyzed [2 + 2 + 2]
      cycloaddition of 1,6-diynes to alpha,omega-dinitriles or electron-deficient
      nitriles or by Ru(II)-catalyzed [2 + 2 + 2] cocyclization of electron-deficient
      alkynes and electron-deficient nitriles. The reactions with dinitriles seem
      likely to proceed via ruthenacyclopentadiene intermediates and the reactions with
      electron-poor nitriles via azaruthenacyclopentadienes. The reaction with
      asymmetric electron-deficient alkynes affords 2,3,6-trisubstituted pyridines in
      good yield.

PMID- 14575492
TI  - Enantioselective trans dihydroxylation of nonactivated C-C double bonds of
      aliphatic heterocycles with Sphingomonas sp. HXN-200.
AB  - The bacterial strain Sphingomonas sp. HXN-200 was used to catalyze the trans
      dihydroxylation ofN-substituted 1,2,5,6-tetrahydropyridines 1 and 3-pyrrolines 4
      giving the corresponding 3,4-dihydroxypiperidines 3 and 3,4-dihydroxypyrrolidines
      6, respectively, with high enantioselectivity and high activity. The trans
      dihydroxylation was sequentially catalyzed by a monooxygenase and an epoxide
      hydrolase in the strain with epoxide as intermediate. While both epoxidation and
      hydrolysis steps contributed to the overall enantioselectivity in trans
      dihydroxylation of 1, the enantioselectivity in trans dihydroxylation of the
      symmetric substrate 4 was generated only in the hydrolysis of meso-epoxide 5. The
      absolute configuration for the bioproducts (+)-3 and (+)-6 was established as
      (3R,4R) by chemical correlations. Preparative trans dihydroxylation of 1a and 4b
      with frozen/thawed cells of Sphingomonas sp. HXN-200 afforded the corresponding
      (+)-(3R,4R)-3,4-dihydroxypiperidine 3a and (+)-(3R,4R)-3,4-dihydroxy pyrrolidine
      6b in 96% ee both and in 60% and 80% yield, respectively. These results represent
      first examples of enantioselective trans dihydroxylation with nonterpene
      substrates and with bacterial catalyst, thus significantly extending this
      methodology in practical synthesis of valuable and useful trans diols.
      Enantioselective hydrolysis of racemic epoxide 2a with Sphingomonas sp. HXN-200
      gave 34% of (-)-2a in >99% ee, which is a versatile chiral building block.
      Further hydrolysis of (-)-2a with the same strain afforded (-)-(3S,4S)-3a in 96%
      ee and 92% yield. Thus, both enantiomers of 3a can be prepared by
      biotransformation with Sphingomonas sp. HXN-200.

PMID- 14575493
TI  - On the aromatic character of the heterocyclic bases of DNA and RNA.
AB  - Studies based on ab initio optimized geometries (at B3LYP/6-311+G** and MP2/6
      311+G** levels) and on experimental structures retrieved from the Cambridge
      Structural Database (CSD) reveal that the nucleobases constituting DNA and RNA
      differ significantly in their aromatic character, as shown by the geometry-based
      index of aromaticity HOMA that ranges from 0.466 for thymine to 0.917 for
      adenine, based on B3LYP/6-311+G** calculations, and 0.495-0.926, respectively, if
      based on the MP2/6-311+G** level. Aromaticity of the bases decreases markedly
      with an increase of the number of double-bond C=X (X = N, O) substituents at the
      rings. H-bonds involving C=O groups in Watson-Crick pairs cause an increase of
      the aromatic character of the rings.

PMID- 14575494
TI  - Conformational restriction of nucleosides by spirocyclic annulation at C4'
      including synthesis of the complementary dideoxy and didehydrodideoxy analogues.
AB  - The concept of spirocyclic restriction, when generically applied to nucleoside
      mimics, allows for the preparation of diastereomeric pairs carrying either a syn-
      or anti-oriented hydroxyl at C-5'. Reported herein are convenient synthetic
      routes to enantiomerically pure 1-oxaspiro[4.4]nonanes featuring fully
      dihydroxylated end products as well as congeners having dideoxy and
      didehydrodideoxy substitution patterns. Notable use is made of the capacity for
      introducing unsaturation in the furanose sector via phenylsulfenylation and the
      incorporation of uracil and thymine by way of their silylated derivatives under
      catalysis with stannic chloride.

PMID- 14575495
TI  - C4'-spiroalkylated nucleosides having sulfur incorporated at the apex position.
AB  - Methodology based on the concept of thionium ion-initiated pinacolic ring
      expansion has been developed for accessing C4'-spirocyclic thionucleosides. The
      readily available racemic ketones 6 and 37 are conveniently resolved via their
      acetals with (R)-mandelic acid. Subsequent reactions beginning with utilization
      of the Pummerer rearrangement lend themselves to functionalization of the
      spirocyclic core and ultimately incorporation of the nucleosidic bases.
      Limitations to this strategy are pointed out. Acquisition of the alpha- and beta
      isomers at C4' is equally facile. Absolute configurational assignments have been
      made possible by X-ray crystallography.

PMID- 14575496
TI  - Highly coupled dyads based on phthalocyanine-ruthenium(II) tris(bipyridine)
      complexes. Synthesis and photoinduced processes.
AB  - A new series of multicomponent ZnPc-Ru(bpy)(3) systems, 1a-c, consisting of a
      zinc-phthalocyanine linked through conjugated and/or nonconjugated connections to
      a ruthenium(II) tris(bipyridine) complex, has been synthesized. The ruthenium
      complexes 1a-c were prepared from phthalocyanines 2a-c, bearing a 4-substituted
      2,2'-bipyridine ligand by treatment with [Ru(bpy)2Cl2].2H2O. Different synthetic
      strategies have been devised to prepare the corresponding dyad precursors (2a-c).
      Compound 2a, for example, with an ethenyl bridge, was synthesized by statistical
      condensation of 4-tert-butylphthalonitrile and 5-[(E)-2-(3,4
      dicyanophenyl)ethenyl]-2,2'-bipyridine (3) in the presence of zinc chloride.
      Compounds 2b and 2c, having, respectively, an amide or an ethynyl bridge, were
      prepared following a different synthetic approach. The method involves the
      coupling of an appropriate 5-substituted-2,2'-bipyridine to an unsymmetrical
      phthalocyanine suitably functionalized with an amino (4) or an ethynyl group (5).
      The photophysical properties of the dyads that are ZnPc-Ru(bpy)3 1a-c and related
      model compounds have been determined by a variety of steady-state (i.e.,
      fluorescence) and time-resolved methods (i.e., fluorescence and transient
      absorption). Clearly, intramolecular electronic interactions between the two
      subunits dominate the photophysical events following the initial excitation of
      either chromophore. These intramolecular interactions lead, in the case of
      photoexcited ZnPc, to faster intersystem crossing kinetics compared to a ZnPc
      reference, while photoexcited [Ru(bpy)3]2+) undergoes a rapid and efficient
      transduction of triplet excited-state energy to the Pc.

PMID- 14575497
TI  - Thermal decomposition of a series of 1,2-diazetines.
AB  - A homologous series of tricyclic diazetines (6a-c), differing by the number of
      methylene groups in the saturated bridges of the fused carbon bicycles, was
      synthesized. The DeltaH++ of decomposition for each of the diazetines to afford
      N2 and the corresponding alkene was determined experimentally: 6a, 31.7; 6b,
      39.3; 6c, 38.8 kcal/mol. The ground-state strain energy of each diazetine was
      estimated utilizing computationally obtained DeltaHf's for each of the
      experimentally investigated diazetines as well as several other diazetines whose
      DeltaH++'s had been previously reported in the literature. The sum of the ground
      state strain energies and DeltaH++'s of decomposition for all of the diazetines
      was nearly constant, with an average value of 59 kcal/mol, suggesting that all of
      the diazetines decompose via the same mechanism. Generally, the higher the ground
      state strain energy of the diazetine, the less the DeltaH++ for decomposition.
      The decomposition transition states for 6a-c and 7 were modeled computationally
      at the RB3LYP/6-311+G(3df,2p)//UB3LYP/6-31+G(d,p) level. The agreement of the
      experimentally determined DeltaH++ values with transition-state energies obtained
      computationally supports the reaction mechanism originally proposed by Yamabe
      that the elimination process occurs by an unsymmetrical, yet concerted,
      transition state with strong biradical character.

PMID- 14575498
TI  - Transacylation of alpha-aryl-beta-keto esters.
AB  - The acyl group of an alpha-aryl-beta-keto ester was readily transferred to N-, O
      , and S-nucleophiles. The transacylation from arylated diethyl 3-oxoglutarate to
      amines led to unsymmetrical malonic acid amide esters in high yields. The present
      reaction proceeded under mild conditions without formation of detectable
      byproducts. Only simple experimental manipulations were required. This reaction
      was also found to be sensitive to steric factors, which enabled the
      chemoselective monoacylation of diamines and amino alcohols without any
      modifications such as protection.

PMID- 14575499
TI  - Use of 13C as an indirect tag in 15N specifically labeled nucleosides. Syntheses
      of [8-13C-1,7,NH2-15N3]adenosine, -guanosine, and their deoxy analogues.
AB  - We have previously reported the use of a 13C tag at the C2 of 15N-multilabeled
      purine nucleosides to distinguish the adjacent-labeled 15N atoms from those in an
      untagged nucleoside. We now introduce the use of an indirect tag at the C8 of
      15N7-labeled purine nucleosides. This tag allows unambiguous differentiation
      between a pair of 15N7-labeled purines in which only one is 13C8 labeled.
      Although the very small C8-N7 coupling (<1 Hz) precludes its direct detection in
      1D 15N spectra, 2D 1H-15N NMR experiments display the large C8-H8 coupling (>200
      Hz) because H8 is coupled to both N7 and C8. The 13C8 atom is introduced by means
      of a ring closure of the exocyclic amino groups of a pyrimidinone using
      [13C]sodium ethyl xanthate. Here, we present methods for the syntheses of [8-13C
      1,7,NH2-15N3]adenosine, -guanosine, and their deoxy analogues.

PMID- 14575500
TI  - Enhancing reactivity of carbonyl compounds via hydrogen-bond formation. A DFT
      study of the hetero-Diels-Alder reaction between butadiene derivative and acetone
      in chloroform.
AB  - To examine how hydrogen-bond (HB) formation involving chloroform solvent
      molecules influences the chemical reactivity of ketones, the hetero-Diels-Alder
      reaction of N,N-dimethyl-1-amino-3-methoxy-1,3-butadiene and acetone has been
      studied by using density functional theory (DFT) at the B3LYP/6-31G level. The
      effects of the chloroform on the activation energies have been modeled by means
      of discrete-continuum models. In the gas phase, the formation of specific HB
      between acetone and one and two chloroform molecules decreases the activation
      barriers from 19.3 to 13.6 and 8.5 kcal/mol, respectively. Inclusion of solvent
      effects by means of combined discrete and polarizable continuum models yields a
      change of molecular mechanism from a concerted to a two-step mechanism, and the
      first nucleophilic step is the rate-limiting step. The corresponding values of
      activation barriers in chloroform are 18.6 kcal/ mol (no HB), 13.5 kcal/mol (one
      HB), and 9.6 kcal/mol (two HBs). These theoretical results account for the
      experimental observation that chloroform accelerates the reaction more markedly
      than more polar aprotic solvent such as acetonitrile. A DFT analysis of the
      global electrophilicity power of the reagents provides a sound explanation about
      the catalytic effects of chloroform.

PMID- 14575501
TI  - Catalytic intermolecular ortho-arylation of phenols.
AB  - The use of rhodium catalysts such as [RhCl(PPh3)3] or [[RhCl(COD)]2] with
      PiPr2(OAr) or P(NMe2)3 co-catalysts allows the ortho-selective intermolecular
      arylation of phenols. The reaction proceeds via orthometalation of P-OAr groups
      and then transesterification liberates the product phenol. When 2-substituted
      phenols are used as substrates, [RhCl(PPh3)3]/iPr2(OAr) mixtures are typically
      the catalysts of choice, whereas for substrates without 2-substitution
      [[RhCl(COD)]2]/P(NMe2)3 mixtures tend to give better results.

PMID- 14575502
TI  - Stabilized and destabilized carbocations in the 1,6-methano[10]annulene series.
AB  - 2-Chloromethyl and 3-chloromethyl-1,6-methano[10]annulene systems solvolyze in
      methanol to give simple substitution products. Solvent effect studies and the
      special salt effect support the involvement of cationic intermediates stabilized
      by the 1,6-methano[10]annulene group. Rate data indicate that the degree of
      cation stabilization greatly exceeds that of naphthyl groups. B3LYP/6-31G
      computational studies also suggest that the cationic intermediates are greatly
      stabilized by the 1,6-methano[10]annulene. By way of contrast to these findings,
      solvolytic and computational studies indicate that the 11-(1,6
      methano[10]annulenyl) cation is a destabilized analogue of the cycloheptatrienyl
      cation. There are no favorable interactions with the annulene ring. Distortions
      from planarity prevent charge delocalization as in the analogous aromatic
      cycloheptatrienyl cation.

PMID- 14575503
TI  - Efficient conversion of substituted aryl thioureas to 2-aminobenzothiazoles using
      benzyltrimethylammonium tribromide.
AB  - The reaction of molecular bromine (Br2) with arylthioureas is known to produce 2
      aminobenzothiazoles (Hugerschoff reaction). We show here that
      benzyltrimethylammonium tribromide (1, PhCH2NMe3Br3), a stable, crystalline
      organic ammonium tribromide (OATB), can be readily utilized as an alternative
      electrophilic bromine source. It is easier to control the stoichiometry of
      addition with an OATB, which minimizes aromatic bromination caused by excess
      reagent. We have developed a direct procedure from isothiocyanates and amines
      using tetrabutylammonium thiocyanate (Bu4NSCN) and PhCH2NMe3Br3 to afford
      functionalized 2-aminobenzothiazoles.

PMID- 14575504
TI  - Conformational dynamics of a bispyridinium cyclophane.
AB  - A complete study of the conformational behavior of 4,8-diaza-3(1,4),9(4,1)
      dipyridina-1,6(1,4)-dibenzenacyclodecaphan-3(1),9(1)-bis(ilium)
      bishexafluorophosphate is described. This study allows us to conclude that the
      process observed by which the different chemical shifts of the pyridinium protons
      show coalescence at a high-temperature 1H NMR is the rotation around the C-N
      bond, whereas the conformational equilibrium between the four conformers is
      produced at low temperature.

PMID- 14575505
TI  - [3 + 2] cycloaddition reactions of 4-alkyl-3-hydroxy-2H-pyrazolo[4,3
      c]isoquinolinium inner salts.
AB  - Heating dipolarophiles with 4-alkyl-3-hydroxy-2H-pyrazolo[4,3-c]isoquinolinium
      hydroxide inner salts results in [3 + 2] cycloaddition across positions 3a and 5
      of the aromatic system to give the [3 + 2] cycloadducts in good yield. When the 4
      alkyl substituent is a 2-acetate ester and the methylene group can be
      deprotonated, a second mode of [3 + 2] cycloaddition becomes available for the
      resulting anion (across the side chain methine group and position 5 of the
      aromatic system) and occurs under basic conditions, allowing either of two modes
      of [3 + 2] cycloaddition to be selected by appropriate choice of reaction
      conditions.

PMID- 14575506
TI  - Synthesis of a highly hindered hydrindanone via alpha-carbonyl radical
      cyclization: enantiospecific formal syntheses of (-)-pinguisenol and (-)-alpha
      pinguisene.
AB  - An enantiospecific synthesis of Schinzer's ketone 3 from (R)-(+)-pulegone via
      alpha-carbonyl radical cyclization was accomplished. This work also constitutes
      an enantiospecific formal syntheses of (-)-pinguisenol and (-)-alpha-pinguisene.
      The intermediate ketone 4 would be useful for the synthesis of other pinguisane
      type sesquiterpenes.

PMID- 14575507
TI  - Head-to-tail oxime cyclization of oligodeoxynucleotides for the efficient
      synthesis of circular DNA analogues.
AB  - A convenient strategy for the synthesis of the analogue of cyclic
      oligodeoxyribonucleotides is presented. The cyclization of the oligonucleotide
      was accomplished through intramolecular oxime bond formation between a 5'
      oxyamine moiety and a 3'-aldehydic group.

PMID- 14575508
TI  - Unexpected single-step formation of 1,2-anti-heterodisubstituted calix[4]arenes
      upon alkylation of a tribenzoyl precursor.
AB  - The selective preparation and complete structural characterization of a small
      series of 1,2-anti-heterodisubstituted calix[4]arenes has been accomplished.
      These compounds were obtained in two steps from unsubstituted p-tert
      butylcalix[4]arene by tribenzoylation and a subsequent one-pot, two-step sequence
      involving alkylation with simultaneous partial deacylation, resulting in
      heterodisubstituted calixarenes carrying an alkyl and an aroyl group. The
      monoalkyl-tribenzoyl intermediate, prior to in situ deprotection, could also be
      isolated.

PMID- 14575509
TI  - Alternative syntheses of the new D2d symmetric tetramethyl tricyclo-
      [3.3.0.0(3,7)]octane-1,3,5,7-tetracarboxylate.
AB  - Two alternative syntheses of the new D2d symmetric tetramethyl
      tricyclo[3.3.0.0(3,7)]octane-1,3,5,7-tetracarboxylate from the known dimethyl 3,7
      dioxo-cis-bicyclo[3.3.0]octane-1,5-dicarboxylate and 1,5-(2,2'-biphenylene)-cis
      bicyclo[3.3.0]octane-3,7-dione are described.

PMID- 14575511
TI  - Catalytic deprotection of protected alcohols in water using low-loading and
      alkylated polystyrene-supported sulfonic acid.
AB  - Catalytic deprotection of various protected alcohols was efficiently conducted
      using a hydrophobic low-loading and alkylated polystyrene-supported sulfonic acid
      (LL-ALPS-SO3H) in water as the sole solvent. Transprotection of an alcohol from a
      silyl ether to the corresponding benzylic ether or ester also proceeded smoothly
      in water.

PMID- 14575510
TI  - Facile Cu(OTf)2-catalyzed preparation of per-O-acetylated hexopyranoses with
      stoichiometric acetic anhydride and sequential one-pot anomeric substitution to
      thioglycosides under solvent-free conditions.
AB  - Solvent-free per-O-acetylation of hexoses with a stoichiometric amount of acetic
      anhydride employing 0.03 mol % Cu(OTf)2 proceeded in high yields (90-99%) at room
      temperature to give exclusively pyranosyl products as an anomeric mixture, the
      alpha/beta ratio of which was dependent on the temperature and amount of catalyst
      used. Sequential anomeric substitution with p-thiocresol in the presence of
      BF3.etherate gave the thioglycosides, isolated exclusively or predominantly as
      one anomer in 66-75% yields.

PMID- 14575512
TI  - Mild electrophilic trifluoromethylation of beta-ketoesters and silyl enol ethers
      with 5-trifluoro methyldibenzothiophenium tetrafluoroborate.
AB  - Cyclic and acyclic beta-ketoesters were efficiently trifluoromethylated with 5
      trifluoromethyldibenzothiophenium tetrafluoroborate in the presence of a phase
      transfer catalyst to afford the corresponding alpha-substituted alpha
      trifluoromethyl beta-ketoesters in good to excellent yields. In a second
      approach, 5-trifluoromethyldibenzothiophenium tetrafluoroborate and
      tetrabutylammonium difluorotriphenylstannate were used for efficient
      electrophilic trifluoromethylation of various silyl enol ethers leading to the
      corresponding alpha-trifluoromethyl ketones in good to high yields.

PMID- 14575513
TI  - Regio- and stereoselective homolytic hydrostannylation of propargyl alcohols and
      ethers with dibutylchlorostannane.
AB  - The Et3B-initiated reaction of gamma-unsubstituted propargyl alcohols with
      dibutylchlorostannane (Bu2SnClH) at low temperature gave (Z)-vinylstannanes with
      high regio- and stereoselectivity. The corresponding alkyl propargyl ethers also
      underwent regio- and stereoselective homolytic hydrostannylation with Bu2SnClH;
      however, the regioselectivity was not so high as that with the propargyl
      alcohols.

PMID- 14575514
TI  - New trimethylaluminum-induced mannich-type reaction of hydrazones.
AB  - Trimethylaluminum addition to N-monoalkyl or N-monoaryl hydrazones followed by
      aldehyde addition leads to the formation of N-alkylated hydrazones in a new
      formal Mannich-type process. Addition compounds were also obtained in moderate
      yields with ketones. The mechanism as well as possible intermediates involved in
      the reaction are discussed.

PMID- 14575515
TI  - Novel efficient preparative method for phthalocyanines from phthalimides and
      phthalic anhydride with HMDS.
AB  - A convenient synthesis of peripherally substituted or unsubstituted
      phthalocyanines having a variety of metals is described. Phthalocyanines can be
      obtained by heating phthalimides or phthalic anhydride with metal salts,
      hexamethyldisilazane, a catalytic amount of p-TsOH, and DMF at 150 degrees C.

PMID- 14575516
TI  - Synthesis of cyclic and acyclic beta-amino acids via chelation-controlled 1,3
      dipolar cycloaddition.
AB  - Isoxazolidines have been synthesized in diastereomeric excess up to 94% via a
      MgBr2-induced chelation-controlled 1,3-dipolar cycloaddition reaction with N
      hydroxyphenylglycinol as a chiral auxiliary. The diastereomerically pure
      isoxazolidines were further transformed into cyclic and acyclic beta-amino acid
      derivatives.

PMID- 14575518
TI  - The pharmacogenetics of immunosuppression for organ transplantation: a route to
      individualization of drug administration.
AB  - Transplantation has transformed the treatment of patients with organ failure in a
      number of clinical settings, and immunosuppressive drug therapy is fundamental to
      its success. However, all the drugs in current use have a narrow therapeutic
      index. Under-dosing can lead to rejection, while over-dosing increases the risks
      of infection, malignant disease, and serious drug-specific adverse effects,
      including diabetes mellitus, nephrotoxicity, hypertension, and hyperlipidemia.
      Heterogeneity in the pharmacokinetics of these drugs makes initial dose
      determination difficult, as there is a poor correlation between dose and blood
      concentration. This results in difficulties in achieving target blood
      concentrations early after transplantation, which are important for reducing the
      rate of immunological rejection. This problem is compounded by the observation
      that neither drug dose nor drug blood concentration accurately predict clinical
      efficacy or toxicity. The main determinant of heterogeneity in dose requirements
      is intestinal absorption of the active drug. The oxidative enzymes, cytochrome
      P450 (CYP) 3A4 and CYP3A5, and the drug efflux pump P-glycoprotein (P-gp) in
      enterocytes regulate this process. Most substrates for the P-gp pump are also
      substrates for the CYP3A enzymes. An efficient barrier to xenobiotic absorption
      is formed by the CYP enzymes and P-gp, and by the two systems working
      synergistically. Genetic polymorphisms have been reported for the genes
      associated with the expression of the CYP3A enzymes and P-gp. Genotyping patients
      for CYP3A genes has the potential to aid the establishment of optimal dosage
      regimens for transplant patients. Genetic polymorphism of the multiple drug
      resistance gene-1 (MDR1, also known as ABCB1) [3435C/T] and the CYP3A5 genes
      (CYP3A5*1, CYP3AP1*1) have the greatest potential to influence the
      pharmacokinetics of immunosuppressants. Homozygosity of the T allele of the MDR1
      3435C/T polymorphism has been associated with reduced enterocyte expression of P
      gp resulting in increased drug absorption. The presence of the CYP3A5*1 allele is
      necessary for the production of a fully catalytic CYP3A5 protein, and also
      influences the ratio of CYP3A4 : CYP3A5 as well as the overall CYP3A catalytic
      activity. The CYP3A4 : CYP3A5 ratio may, in turn, influence the pattern of drug
      metabolites formed. Heterogeneity in the production of active and inactive
      metabolites has implications for both the pharmacokinetics and pharmacodynamics
      of these drugs.Gene frequencies and drug dose requirements differ between ethnic
      groups. Ethnic differences in dose requirements for immunosuppressants have been
      discussed widely. However, ethnicity is a rather crude marker for genotype.
      Pharmacogenetic typing offers the possibility of significant improvement in the
      individualization of immunosuppressive drug prescribing with reduced rates of
      rejection and toxicity.

PMID- 14575520
TI  - Genetic polymorphisms in cytokine and adhesion molecule genes in coronary artery
      disease.
AB  - Both inflammation and genetics play an important role in the pathogenesis of
      atherosclerosis and coronary artery disease. Epidemiological studies have
      investigated the association between coronary artery disease (CAD) and gene
      polymorphisms of the inflammatory molecules tumor necrosis factors (TNF) alpha
      and beta, transforming growth factors (TGF) beta-1 and beta-2, interleukin (IL)-1
      and its receptor antagonist (IL-1ra), CD14 (the receptor for lipopolysaccharide),
      P- and E-selectins, and platelet endothelial cell adhesion molecule (PECAM)-1.
      Current evidence suggests that the TNF polymorphisms explored so far are not
      linked to CAD. The majority of studies conducted showed no significant
      association between TGFbeta-1 and coronary atherosclerosis, but the data
      currently available are somewhat controversial. Some polymorphisms may increase
      the risk of myocardial infarction (MI) within specific ethnic groups or in
      certain populations. The association between the IL-1 system and atherosclerosis
      is complex and may vary as a result of a number of factors, such as stage of
      disease, clinical phenotype, and possibly population characteristics. The E
      selectin gene (SELE) Arg128, 98T, and Phe554 alleles may increase the risk of
      atherosclerosis, but not necessarily the risk of MI. This association seems to be
      more pronounced in younger patients. The PECAM1 Leu125Val and Ser563Asn
      polymorphisms may increase the risk of atherosclerosis but not necessarily of MI.
      This association may be especially important in patients with a low risk for
      developing atherosclerosis. Current data indicate that screening for CD14-260C/T
      genotypes is unlikely to be a useful tool for risk assessment and it remains
      unclear whether CD14 polymorphisms significantly increase the risk of MI. The
      associations between candidate gene polymorphisms and CAD are complex as a
      consequence of pleiotropy, variations with age, selection due to the high
      lethality of the disease, and interactions with other genes and environmental
      factors. Nonetheless, although the current data is preliminary and partly
      conflicting, it does provide some evidence that alterations in the genetics of
      the inflammatory system may modify the risk of CAD.

PMID- 14575519
TI  - Genetics of response to proton pump inhibitor therapy: clinical implications.
AB  - Proton pump inhibitors (PPIs) are highly effective agents for the treatment of
      gastric acid-related disorders. They are metabolized by the cytochrome P450 (CYP)
      system, mainly via the enzyme CYP2C19. A genetically determined defect in this
      pathway results in impaired metabolism of PPIs, giving rise to three distinct
      phenotypes: rapid extensive (fast), extensive (medium), and poor (slow)
      metabolizers. These genetic mutations are more common in certain races, and there
      is, therefore, considerable inter-individual and -ethnic variation in the
      capacity to metabolize PPIs. The incidence of mutant alleles in a population
      treated for acid-related disorders may influence the efficacy of the treatment,
      with clinical implications for the prescribers of PPIs. Therapeutic failure, such
      as lack of symptom relief, or ineffective Helicobacter pylori eradication, can
      occur in rapid metabolizers who will have less available drug at a given dose.
      Conversely, poor metabolizers may be at risk of over-treatment, with increased
      incidence of adverse effects and unnecessary financial burden. Approaches to this
      problem include phenotyping or, preferably, genotyping patients prior to
      treatment with PPIs. This will allow tailoring dose regimens to the individual's
      metabolic capacity. An alternative strategy is the development of drugs that are
      either metabolized by genotype-independent pathways or are less susceptible to
      inter-individual genetic variation. Non-racemic PPIs fall into the latter
      category, and the first such agent, esomeprazole, is now commercially available.

PMID- 14575521
TI  - Molecular mechanisms of migraine: prospects for pharmacogenomics.
AB  - Migraine is a common complex disorder that affects a large portion of the
      population and thus incurs a substantial economic burden on society. The disorder
      is characterized by recurrent headaches that are unilateral and usually
      accompanied by nausea, vomiting, photophobia, and phonophobia. The range of
      clinical characteristics is broad and there is evidence of comorbidity with other
      neurological diseases, complicating both the diagnosis and management of the
      disorder. Although the class of drugs known as the triptans (serotonin 5
      HT(1B/1D) agonists) has been shown to be effective in treating a significant
      number of patients with migraine, treatment may in the future be further enhanced
      by identifying drugs that selectively target molecular mechanisms causing
      susceptibility to the disease.Genetically, migraine is a complex familial
      disorder in which the severity and susceptibility of individuals is most likely
      governed by several genes that may be different among families. Identification of
      the genomic variants involved in genetic predisposition to migraine should
      facilitate the development of more effective diagnostic and therapeutic
      applications. Genetic profiling, combined with our knowledge of therapeutic
      response to drugs, should enable the development of specific, individually
      tailored treatment.

PMID- 14575522
TI  - Beyond the human genome: examples of nuclear receptor analysis in model organisms
      and potential for drug discovery.
AB  - The nuclear receptor (NR) superfamily is a large group of related,
      pharmacologically important receptors, comprising the targets for over 10% of
      commonly prescribed drugs. Cross-genome analysis of NR sequence, structure, and
      biological function, provides an important source of information on the function
      of human NRs and thus plays a role in NR drug discovery. For example, research on
      the pregnane X receptor (PXR; NR1I2), constitutive androstane receptor (CAR;
      NR1I3), hepatocyte nuclear factor 4 (HNF4; NR2A1), and farnesoid X receptor (FXR)
      illustrate how the study of nonhuman orthologs has provided new insights into NR
      biology and has increased our understanding of human NRs and orphan NR function.
      Understanding differences between humans and pharmacological model species may
      provide useful tools for the development of new NR-binding drugs.

PMID- 14575523
TI  - Cytochrome P450 2J2 polymorphism in healthy Caucasians and those with diabetes
      mellitus.
AB  - OBJECTIVE: Cytochrome P450 (CYP) 2J2 plays an important role in the biosynthesis
      of the biologically active cis-epoxyeicosatrienoic acids. An allelic variant
      named CYP2J2*6, which encodes an enzyme that is almost inactive in the metabolism
      of arachidonic acid, has recently been described. We investigated the frequency
      of the CYP2J2*6 variant in a Caucasian population and the relationship between
      this polymorphism and the development of micro- and macrovascular complications
      and hypertension in patients with type 1 or type 2 diabetes mellitus. METHODS:
      Genomic DNA was extracted from peripheral blood cells and the fragment containing
      the A/T single nucleotide polymorphism at position 25 661 in exon 8 of the CYP2J2
      gene was amplified. The 532 bp amplified product was subsequently digested with
      Tsp509I and analyzed on 12% polyacrylamide gel electrophoresis. RESULTS: In the
      whole population, the frequency of the CYP2J2*6 allele was 0.0064 and the
      frequency of the CYP2J2*1 allele was 0.9936. Genotype distribution did not show
      significant differences between controls and patients with type 1 or type 2
      diabetes. No homozygotes for CYP2J2*6 allele were found. No association was found
      between this allele and complications or hypertension in either type of diabetes.
      CONCLUSION: The CYP2J2*6 allele is rare in the Caucasian population, and no
      association is inferred between this allelic variant and diabetic complications.

PMID- 14575524
TI  - Amino acid domains control the circulatory residence time of primate
      acetylcholinesterases in rhesus macaques (Macaca mulatta).
AB  - An array of 13 biochemically well defined molecular forms of bovine, human and
      newly cloned rhesus macaque (Macaca mulatta) AChEs (acetylcholinesterases)
      differing in glycosylation and subunit assembly status were subjected to
      comparative pharmacokinetic studies in mice and rhesus macaques. The circulatory
      lifetimes of recombinant bovine, macaque and human AChEs in mice were governed by
      previously determined hierarchical rules; the longest circulatory residence time
      was obtained when AChE was fully sialylated and tetramerized [Kronman, Chitlaru,
      Elhanany, Velan and Shafferman (2000) J. Biol. Chem. 275, 29488-29502; Chitlaru,
      Kronman, Velan and Shafferman (2001) Biochem. J. 354, 613-625]. In rhesus
      macaques, bovine molecular forms still obeyed the same hierarchical rules,
      whereas primate AChEs showed significant deviation from this behaviour. Residence
      times of human and rhesus AChEs were effectively extended by extensive
      sialylation, but subunit tetramerization and N-glycan addition had a marginal
      effect on their circulatory longevity in macaques. It appears that the major
      factor responsible for the differential pharmacokinetics of bovine and primate
      AChEs in macaques is related to differences in primary structure, suggesting the
      existence of a specific mechanism for the circulatory clearance of primate AChEs
      in rhesus macaques. The 35 amino acids that differ between bovine and primate
      AChEs are clustered within three defined domains, all located at the enzyme
      surface, and may therefore mediate the facilitated removal of primate
      cholinesterases specifically from the circulation of monkeys. These surface
      domains can be effectively masked by poly(ethylene glycol) appendage, resulting
      in the generation of chemically modified human and macaque AChEs that reside in
      the circulation for extraordinarily long periods of time (mean residence time of
      10000 min). This extended residence time is similar to that displayed by native
      macaque butyrylcholinesterase (9950 min), which is the prevalent cholinesterase
      form in the circulation of adult macaques.

PMID- 14575525
TI  - Genomic organization and linkage via a bidirectional promoter of the AP-3
      (adaptor protein-3) mu3A and AK (adenosine kinase) genes: deletion mutants of AK
      in Chinese hamster cells extend into the AP-3 mu3A gene.
AB  - The cDNA and genomic DNA for the mu3A subunit of the AP-3 (adaptor protein-3)
      complex were cloned from Chinese hamster cells. The AP-3 mu3A genes in Chinese
      hamster, human and mouse each comprise nine exons and eight introns, with all
      introns located in identical positions in the species studied. The AP-3 mu3A
      genes in these species are linked in a head-to-head fashion with the gene for the
      purine salvage pathway enzyme AK (adenosine kinase). These genes share the first
      exon, and a 512 bp fragment covering the intervening untranslated sequence has
      the characteristic of a CpG island promoter, and it effectively carried out
      transcription in both directions. Deletion studies indicate that this region
      contains both positive and negative regulatory elements affecting transcription
      of these genes. In comparison with the AP-3 mu3A gene (27 kb), the AK gene in
      human is very large (558 kb), with average exon and intron lengths of approx. 100
      bp and 55.7 kb respectively. The ratio of non-coding to coding sequence in the
      human AK gene is >550, which is the highest reported for any gene. We also
      present evidence that a number of AK- mutants of Chinese hamster ovary cells
      contain large deletions that affect both of these genes. In addition to lacking
      part of the AK gene, two of these mutants also lacked all of the exons and
      introns corresponding to the AP-3 mu3A gene. These mutants should prove useful in
      elucidating the role of AP-3 mu3A in vesicle-mediated protein sorting--a process
      that is altered in Hermansky-Pudlak syndrome. Detailed phylogenetic analysis of
      the micro family of proteins presented here also provides insight into how
      different AP complexes are related and may have evolved.

PMID- 14575529
TI  - Mapping perception to action in piano practice: a longitudinal DC-EEG study.
AB  - BACKGROUND: Performing music requires fast auditory and motor processing.
      Regarding professional musicians, recent brain imaging studies have demonstrated
      that auditory stimulation produces a co-activation of motor areas, whereas silent
      tapping of musical phrases evokes a co-activation in auditory regions. Whether
      this is obtained via a specific cerebral relay station is unclear. Furthermore,
      the time course of plasticity has not yet been addressed. RESULTS: Changes in
      cortical activation patterns (DC-EEG potentials) induced by short (20 minute) and
      long term (5 week) piano learning were investigated during auditory and motoric
      tasks. Two beginner groups were trained. The 'map' group was allowed to learn the
      standard piano key-to-pitch map. For the 'no-map' group, random assignment of
      keys to tones prevented such a map. Auditory-sensorimotor EEG co-activity
      occurred within only 20 minutes. The effect was enhanced after 5-week training,
      contributing elements of both perception and action to the mental representation
      of the instrument. The 'map' group demonstrated significant additional activity
      of right anterior regions. CONCLUSION: We conclude that musical training triggers
      instant plasticity in the cortex, and that right-hemispheric anterior areas
      provide an audio-motor interface for the mental representation of the keyboard.

PMID- 14575530
TI  - Variations in the lipid profile of patients with chronic renal failure treated
      with pyridoxine.
AB  - BACKGROUND: Hyperhomocysteinemia and lipid abnormalities are commonly found in
      patients with chronic renal failure; both are recognized as risk factors for
      atherosclerosis. The homocysteine-lowering effect of pyridoxine is controversial.
      This study was performed to determine the effect of a high dose of pyridoxine
      (300 mg i.v. three times a week) on plasma and red blood cell lipid profile and
      plasma homocysteine concentration in twelve chronic renal failure patients on
      regular hemodialysis. Fasting blood samples were taken at the beginning of the
      study (basal 1), after 30 and 60 days of treatment and 4 months after withdrawal
      (basal 2). RESULTS: Pyridoxine supplementation induced a significant decrease in
      total plasma homocysteine level and also a lowering effect in plasma total
      cholesterol and triglycerides. These biochemical data increased when the samples
      were taken at basal 2, reaching the levels obtained at the beginning of the
      experiment. LDL cholesterol increased whereas HDL cholesterol was reduced during
      the treatment. In erythrocyte membranes vitamin B6 therapy enhanced the
      cholesterol/phospholipid ratio as well as the fluorescence anisotropy of diphenyl
      hexatriene. CONCLUSIONS: We conclude that high doses of pyridoxine represent an
      effective strategy to ameliorate both plasma homocysteine levels and lipid
      profiles in chronic renal failure patients, protecting them from atherosclerosis.
      Further research using a long-term treatment would be necessary in an attempt to
      restore the fatty acid pattern and the fluidity of red cell membranes.

PMID- 14575532
TI  - [Detection of the anti-SARS-coronavirus specific antibody levels in 156 SARS
      patients].
AB  - The objective of this study was to explore the development of IgG and IgM against
      SARS CoV and characteristics of changes of antibody titers in patients with
      severe acute respiratory syndrome (SARS) and to search the opportunity for
      collecting specific anti-serum from convalescent patients with SARS. The anti
      SARS-coronavirus specific antibody levels in 156 SARS patients were measured with
      ELISA. The results showed that the total positive rates of IgG and IgM were 75.6%
      and 41.7% respectively, and the negative rate of both IgG and IgM was 23.7%. The
      average titers of IgG and IgM antibody in positive samples were 18.23 +/- 24.72
      and 2.18 +/- 1.13, respectively. There was no significant correlation between the
      titers of IgG/IgM and sex, age, course of diseases and duration of body
      temperature recovery. It was concluded that not all SARS patients could produce
      the anti-SARS-coronavirus specific antibody. The titers of the anti-body are
      diversified even if the antibodies have been emerged in them. In order to obtain
      effective anti-serum, the titers of antibody must be tested just before
      collection of convalescent serum, and it ensures the therapeutic effect and
      provides a measurable index for clinical transfusion.

PMID- 14575531
TI  - At the crossroads: AMP-activated kinase and the LKB1 tumor suppressor link cell
      proliferation to metabolic regulation.
AB  - The tumor suppressor kinase LKB1 has been identified as a physiologic activator
      of the key metabolic regulator 5'-AMP-activated protein kinase, establishing a
      possible molecular link between the regulation of metabolism and cell
      proliferation.

PMID- 14575533
TI  - [Comparative study of differentially expressed genes in mouse bone marrow and
      fetal liver cells].
AB  - Hematopoiesis undergoes several migrations from yolk sac to liver and spleen, and
      finally bone marrow until the end of life. A number of investigations have
      demonstrated that the hematopoietic microenvironment plays very important role in
      this process. However, the exact mechanisms remain unknown. In order to
      systematically analyze and understand the role of hematopoietic microenvironment
      in the regulation and control of hematopoiesis, a microarray containing 588
      complementary DNAs was used to compare the gene expressions between those in
      murine fetal liver and bone marrow cells. The results obtained from array
      hybridization were analyzed and reconfirmed by using bioinformatics and RT-PCR as
      well as Northern blot. The results showed that 65 and 131 genes were relatively
      high expressed in bone marrow and fetal liver cells respectively among 588 known
      genes in the array-membrane. According to the survey in the PubMed, 39 out of
      bone-marrow-expressed genes and 71 in fetal-liver-expressed genes were closely
      related to the hematopoiesis. Further reconfirmation by RT-PCR or Northern blot
      has demonstrated that CD18, CD44 an d PSGL-1 genes chosen for analysis were
      highly expressed in adult bone marrow, but unexpressed or lower expressed in
      fetal liver cells, resulting in high similarity to the array results. Moreover,
      the expressions of CD18 and CD44 in fetal liver were down-regulated with the
      increment of gestational age. In conclusion, the gene expressions in bone marrow
      and fetal liver cells are obviously different, some of the genes are down
      regulated at the different stages of ontogeny. The different gene expression
      levels between bone marrow and fetal liver, especially those genes closely
      related to the hematopoiesis, may be the molecular basis for the explanation of
      why hematopoietic stem cells derived from different tissues have different
      characterizations as well as the differences from the beginning and terminating
      of fetal liver hematopoiesis, and why hematopoietic stem cells derived from fetal
      liver is tremendously difficult to be grafted in bone marrow.

PMID- 14575534
TI  - [Effects of antisense oligodeoxynucleotides of human telomerase reverse
      transcriptase gene on telomerase activity in CEM cell line].
AB  - To explore the effect of antisense phosphorothioate oligodeoxynucleotide (ASODN)
      of human telomerase reverse transcriptase (hTERT) gene on telomerase activity in
      CEM cells, PCR enzyme-linked immunoassay was used to determine telomerase
      activity. The expression levels of hTERT mRNA and protein were assayed by RT-PCR
      and immunofluorescence assay using fluoresce isothiocyanate label respectively.
      The results showed that the expression levels of hTERT mRNA and protein in CEM
      cells decreased with time after hTERT ASODN treatment. There was no difference in
      hTERT mRNA and protein levels between control and sense oligodeoxynucleotide
      treated cells. Telomerase activity decreased when CEM cells were treated with
      ASODN for 48 hours. Telomerase activity of CEM cells was significantly inhibited
      when treated with ASODN for 72 hours. There was no difference in telomerase
      activity levels between control and hTERT sense oligodeoxynucleotide-treated
      cells. These results suggested that hTERT ASODN inhibited telomerase activity of
      CEM cells.

PMID- 14575535
TI  - [Inhibition of proliferation in Jurkat cells transfected with exogenous HCAP1
      gene].
AB  - HCAP1 is a novel hepatic cancer related gene located on human chromosome 17p13.3.
      The loss of heterozygosity occurred at 17p13.3 in various human cancers. In order
      to investigate the effects of exogenous HCAP1 gene products on cell proliferation
      of T lymphoma Jurkat cell line, HCAP1 gene! was transfected into Jurkat cells
      mediated by liposome, and the cells stably expressing exogenous HCAP1 were
      screened with G418. The effects of HCAP1 products on cell proliferation were
      assessed by viable cell count, cell growth curve and colony formation assay in
      soft agar. The results showed that the HCAP1 transgenic Jurkat cells displayed
      slow growth rate, extended doubling time and reduced colony formation capability,
      as compared with the cells transfected with pBK/CMV empty vector (P < 0.01). It
      is concluded that exogenous HCAP1 gene products could inhibit the proliferation
      of Jurkat cells.

PMID- 14575536
TI  - [Exploration of methodology for assay of single nucleotide polymorphism in
      thiopurine methyltransferase gene].
AB  - The aim of the present study was to gain an insight into the thiopurine
      methytransferase (TPMT) genotyping assay, which was based on polymerase chain
      reaction (PCR), allele-specific PCR, restriction digestion of PCR products,
      denaturing high-performance liquid chromatography (DHPLC) and SNaPshot sequencing
      and in combination with direct DNA sequencing. Among the f our methods to test
      TPMT genetic SNPs based on PCR, allele specific PCR was not able to differentiate
      wild type from varied type. BsiYI, MwoI and AccI to digest PCR products were used
      so that SNP in TPMT exon 5, 7 and 10 tested. It showed that there were no
      differences between the results of digestion of PCR products and those of DNA
      sequence analysis. Therefore, this method was reliable. But some other methods
      were still needed to look for a compensation, because no restriction map changing
      resulted from the 2 SNPs in TPMT promotor was found. As to the results of DHPLC,
      those for the screening of TPMT exon-5 and -10 for SNPs were the same as
      restriction analysis of PCR products and direct DNA sequencing. But the variation
      of the heterozygotes in exon-7 was high, which was different from the results of
      direct DNA sequencing. After changing the Tm of DNA step by step, It was found
      that all the samples showed single peak when the temperature was 54 degrees C.
      But this result was unbelievable because a heterozygote in exon 7 as positive
      control could not be found. Therefore, it was necessary to test the sensitivity
      and accuracy of DHPLC, though DHPLC could be used as an effective method of SNPs
      screening. The results of the SNaPshot sequencing were also same as those of
      restriction analysis of PCR products and direct DNA sequencing. And the results
      showed that the bases of TPMT promoter -91 and -168 were G, instead of A and T.
      The results of the four methods to detect TPMT genetic SNPs based on PCR showed
      that SNPs analysis technique should be a combination of the techniques above
      mentioned. One technique alone could not satisfy the need in clinics and
      research. The compensation of each other was very important.

PMID- 14575537
TI  - [Change of PML/PML-RARalpha protein during treatment with tetraarsenic
      tetrasulfide (As4S4) in patients with acute promyelocytic leukemia].
AB  - In order to explored the change of PML/PML-RARalpha protein during tetraarsenic
      tetrasulfide (As4S4) treatment, acute promyelocytic leukemia (APL) cells from a
      group of newly diagnosed APL patients were examined by indirect
      immunofluorescence staining with anit-PML monoclonal antibody. The results showed
      that all samples typically presented many microspeckle signals throughout the
      nucleus before treatment. The redistribution occurred as early as on the second
      day after As4S4 treatment, which revealed loss of microspeckles with the
      presentation of a few large speckles. Anti-PML staining also emerged in the
      perinuclear cytoplasm. At last, microspeckles and large speckles all disappeared.
      When the therapy was combining all-trans-retinoic acid (ATRA) with As4S4, similar
      results were obtained. However, APL cells from patients treated with ATRA alone
      performed totally different appearance, presenting microspeckles and large
      speckles at the same time, followed with entirely large speckles. The conclusion
      is that As4S4 makes redistribution of PML/PML-RARalpha protein in leukemic cells
      from APL patients during the treatment, which is quite different from that during
      the treatment of ATRA.

PMID- 14575538
TI  - [Clinical analysis of retinoic acid syndrome developed in 11 patients with acute
      promyelocytic leukemia].
AB  - To explore the clinical features, risk factors an d treatment of retinoic acid
      syndrome (RAS) in patients with acute promyelocytic leukemia (APL) treated with
      retinoic acid, the clinical and laboratory data of 11 APL patients with RAS were
      retrospectively analysed. The results showed that earlier and more common
      symptoms of RAS were successively dyspnea (11/11), fever (10/11) and hydrothorax
      (6/11). Higher WBC count (> or = 15.0 x 10(9)/L) in the course of treatment of
      all-trans retinoic acid susceptible to develop RAS (9/11). The RAS patients were
      treated with dexamethasone without discontinuing the treatment of retinoic acid,
      complete remission was achieved in 10 cases and one patient died from
      disseminated intravascular coagulation. It is concluded that the identification
      and dexamethasone treatment of RAS in earlier period are extremely important for
      obtaining better clinical curative effect, and it does not influence therapeutic
      effect of continuing application of retinoic acid.

PMID- 14575539
TI  - [Expression of lung resistance protein and multidrug resistance protein genes in
      bone marrow cells of acute leukemia patients and its clinical significance].
AB  - To study the expression of lung resistance protein (LRP) and multidrug resistance
      protein (MRP) genes in bone marrow cells in patients with acute leukemia and its
      clinical significance, expression of LRP and MRP mRNA in bone marrow cells from
      47 cases of acute leukemia, including 10 refractory or relapsed cases, and 7
      normal individuals were determined by semi-quantitative reverse transcription
      polymerase chain reaction (RT-PCR). The result s showed that expression of LRP
      gene was negative in normal individuals. LRP mRNA level in newly treated cases of
      acute myelocytic leukemia and refractory or relapsed cases was significantly
      higher than that in normal individuals, increased LRP mRNA level has correlation
      with lower sensitivity to initial chemotherapy and was associated with reduced
      overall survival rate. Complete remission (CR) rate in LRP positive patients was
      lower than that in negative cases. The level of LRP expression was correlated
      with that of MRP mRNA. In conclusion, the expression of LRP mRNA can predict the
      treatment outcome and prognosis for acute myelocytic leukemia, prognosis was even
      worse in LRP and MRP linked expression cases, therefore, LRP was an important
      resistant factor, determination of LRP and MRP expression can help us to evaluate
      the prognosis and choose chemotherapy program.

PMID- 14575540
TI  - [Effects of human fibroblastoid stromal cell line on proliferation of HL-60 cells
      and expression of VEGF].
AB  - To investigate the effects of normal human bone m arrow fibroblastoid stromal
      cell line (HFCL) on the proliferation of acute myeloid leukemia cell line HL-60
      and expression of vascular endothelial growth factor (VEGF), establishing
      coculture system of leukemia cell line HL-60 and HFCL, growth data was obtained
      by cell counting. Mitotic index (MI) was observed under Wright-Giemsa staining.
      Flow cytometry and Western blot were used as assays for cell cycle and expression
      of proliferating cell nuclear antigen (PCNA) separately. VE GF levels were
      evaluated by using commercial ELISA kits. The results showed that compared with
      HL-60 cells without HFCL cells, the proliferation of HL-60 cells in direct
      contact with HFCL cells and with HFCL cells separated by transwell was inhibited.
      The MI of HL-60 cells without HFCL cells was highest followed by HL-60 cells
      separated by transwell and HL-60 cells in direct contact with HFCL cells. The
      expression of PCNA in HL-60 cells with HFCL cells were lower than HL-60 cells
      without HFCL cells. Meanwhile, the percentage of HL-60 cells in G1 phase
      cocultured with HFCL cells was higher than that without HFCL cells while the
      percentage of Sphase cells was lower. The levels of VEGF in HL-60 cells with HFCL
      cells were lower than that in HL-60 cells alone. In conclusion, the normal bone
      marrow fibroblastoid stromal cells inhibited the proliferation of HL-60 cells as
      well as the expression of VEGF.

PMID- 14575541
TI  - [Effects of hexamethylene bisacetamide on cell cycle and expression of its
      regulatory proteins in HL-60 cells].
AB  - Hexamethylene bisacetamide (HMBA) is referred as a differentiation-inducer for
      the clinical treatment of acute myeloid leukemia and myelodysplastic syndrome.
      However, the molecular mechanism of the effects of HMBA on myeloid leukemic cells
      remains unknown. In this study, the effects of HMBA on cell cycle and expression
      of cell cycle regulatory proteins in HL-60 cell were investigated in order to
      explore its pharmacological mechanism. The altered distribution of cell cycle and
      expression of its regulatory proteins (cyclin D, cyclin E and p27) in HL-6 0 cell
      induced by HMBA were analyzed by flow cytometry. The effects on transcription for
      mRNA of CKI p15, p16 and p27 in HL-60 cell were further studied by RT-PCR. The
      results showed that HMBA could mainly commit HL-60 cell to G0/G1 arrest and the
      significantly decreased endocytic cyclin E protein and increased cyclin D/p27
      protein after HMBA treatment were found. There was no expression of p15, p16 mRNA
      in untreated HL-60 cell and 3 mmol/L of HMBA could make them expressed after
      exposed for 24 h or 48 h respectively. The expression of p27 mRNA was positive
      and no obviously different in untreated HL-60 cells exposed for 24 h, 48 h and 72
      h. These results suggested that one of the pharmacological mechanisms of HMBA was
      to elevate the expression of p27 and reduce the cyclin E expression as well as to
      activate the expression of p15, p16 gene mRNA, that arrested cell at G0/G1 and
      exerted its effects of anti-proliferation.

PMID- 14575542
TI  - [Enhanced apoptosis-inducing effect of etoposide on leukemic cell lines M-07e and
      TF-1 by the proteasome inhibitor Z-LLL-CHO].
AB  - Recent researches indicate that ubiquitin-protea some pathway plays an important
      role in apoptosis regulation. Proteasome inhibitors induce apoptosis in many
      kinds of neoplastic cells, thus provide a great opportunity for exploring synergy
      of proteasome inhibitors and other apoptosis-inducing agents. In this study, the
      effect of the proteasome inhibitor Z-LLL-CHO combined with etoposide (VP16) on
      leukemic cell lines M-07e and TF-1 was investigated by MTT assay, trypan blue
      exclusion, flow cytometry and Western blot. The results showed that the
      combination of Z-LLL-CHO and VP16 was much more effective than either agents
      alone in promoting cytotoxicity in both cell lines evaluated. Accumulation of
      cells in S + G2/M phase of the cell cycle was observed in the cells treated with
      VP16 and Z-LLL-CHO alone, while apparent increase of sub-G0/G1 fraction was
      detected in cells treated with combination of the agents. The cleavage of Bcl-2
      into a shortened 22 kD fragment was detected in M-07e cells exposed to either
      agents alone, and the fraction of 22 kD fragment was increased in the cells
      treated with combination of the agents. In conclusion, the combination of Z-LLL
      CHO and VP16 enhanced their individual cytotoxic effect by inducing apoptosis, in
      which increase of S + G2/M fraction in cell cycle as well as the enhanced
      cleavage of Bcl-2 are the possible mechanism of the additive effect on leukemic
      cells by Z-LLL-CHO and VP16.

PMID- 14575543
TI  - [Establishment of a human CD30+ anaplastic large cell lymphoma cell line and its
      biological characteristics].
AB  - A CD30+ anaplastic large cell lymphoma (ALCL) cell line was established from the
      mononuclear cells isolated from pleural effusion of a patient with non-Hodgkin's
      lymphoma. The cell line's biological characteristics were analyzed. The results
      showed that the established cell line could survive and proliferate in RPIM 1640
      medium; the Wright-Giemsa-stained cells were exactly similar to malignant cells
      of CD30+ ALCL in morphology, with many diffuse virus granules in cytoplasm; the
      cytochemical staining of the cells showed the following reactivity pattern:
      positive for acid phosphatase (ACP) and periodic acid-Schiff (PAS), negative for
      peroxidase (POX), myeloperoxidase (MPO) and platelet peroxidase (PPO). The
      immunoprofile of the cells was positive for CD45, HLA-DR, CD30 and negative for
      EMA, CD34, CD38, CD2, CD3, CD4, CD7, CD8, CD10, CD15, CD19 and CD20. The
      cytogenetic analysis showed complicate d qualitative and quantitative abnormality
      of chromosomes, without typical t(2;5). It is concluded that the established cell
      line is CD30+ anaplastic large cell lymphoma cell line.

PMID- 14575544
TI  - [Mechanism of action of protease-activated receptors 1 and 4 in platelet
      activation].
AB  - This study was designed to compare the effects of protease-activated receptor 1
      (PAR-1) and protease-activated receptor 4 (PAR-4) to the expression of platelet
      surface GPIbalpha and cytoskeleton reorganization, then to investigate the role
      of PARs in platelet signal transmission. PAR1 (25 micromol/L) and PAR4 (250
      micromol/L) were used to stimulate platelet at different time points (0 - 60
      minutes), and the platelet surface GPIbalpha, actin and myosin and P-selectin
      were detected with flow cytometry, the alteration of GPIbalpha, actin and myosin
      in cytoskeleton was compared by Western blot, the membrane cytoskeleton followed
      GPIbalpha immunoprecipitation was analyzed. The results showed that an increase
      of P-selectin and reversible decrease of GPIbalpha expression were obtained after
      platelet activation by PAR1 o r PAR4, and a different kinetics of redistribution
      of GPIbalpha was found for the two peptides all over the time course (P < 0.05).
      PAR1 acted more potently and rapidly than PAR4, but the effect of PAR4 persisted
      longer in the course of platelet activation. Meanwhile, there was a transient
      change of actin, myosin and GPIbalpha in cytoskeleton proteins. Similar
      redistribution was also found in GPIbalpha/myosin and GPIbalpha/actin
      association. It is concluded that PAR1 and PAR4 possess an important role in
      platelet signal transmission. Either of the receptors can mediate platelet
      activation and GPIbalpha redistribution, which is correlated with cytoskeleton
      reorganization. PAR1 acts more rapidly, and effect of PAR4 persists longer.

PMID- 14575545
TI  - [Comparison of the clonal expansion of TCR Vbeta T cells in patients with acute
      promyelocytic leukemia in vivo and in vitro].
AB  - In order to analyze the distribution and clonal expansion of TCR Vbeta subfamily
      T cells in patients with acute promyelocytic leukemia (APL) in vivo and in vitro
      after T cell culture, the peripheral blood mononuclear cells from 3 APL patients
      were expanded by rhIL-2 and anti-CD3 antibody using liquid T lymphocytes culture
      technique. The complementary determining region 3 (CDR3) of TCR beta with
      variable region genes was amplified in T cells from 3 APL cases before and after
      T cell culture by using RT-PCR. The positive products were further analyzed to
      identify the clonality of T cells by genescan. The results showed that only a
      part of 24 Vbeta subfamilies was detected in T cells from the patients, and some
      Vbeta subfamily T cells could be identified after T cells culture. The clonal
      expansion T cells in some TCR Vbeta subfamilies could be found in all patients.
      The similar oligoclonal expansion of Vbeta1, Vbeta3, Vbeta7, Vbeta16 and Vbeta20
      T cells was detected in two cases at different time points after T cell culture.
      It is concluded that the restricted expression of TCR Vbeta subfamily in T cells
      from patients might be the common feature in leukemia. Some Vbeta subfamily T
      cells could be induced after T cells culture in vitro. The continual clonal
      expansion of TCR Vbeta subfamily T cells at different time points after T cells
      culture could be a specific immune response of patients T cells related to the
      specific APL cell associated antigen.

PMID- 14575546
TI  - Allogeneic peripheral blood hematopoietic stem cell transplantation in malignant
      hematopoietic diseases.
AB  - To evaluate the use of allogeneic peripheral blood stem cell transplantation
      (allo-PBSCT) for treatment of acute and chronic leukemia, from March 1997 to
      January 2003, 21 adult patients with malignant hematopoietic diseases underwent
      allo-PBSCT from HLA-identical siblings (19 patients) and haplo-identical mother
      (one) and one B point site mismatched sibling (one). All donors were mobilized
      with G-CSF for 4 days and peripheral blood stem cells were collected by CS-3000
      separator. The conditioning regimen included the high dose combination
      chemotherapy and TBI. Cyclosporine-A (CsA) plus a short course of MTX was used
      for GVHD prophylaxis in all patients. The results showed that after trans
      plantation, median time for the recovery of granuocyte > or = 0.5 x 10(9)/L and
      platelets > or = 20 x 10(9)/L were 12 (10 - 20) and 15 (11 - 35) days,
      respectively. Acute GVHD was observed in 8/17 patients (47%), of which one
      transplanted from HLA-haploidentical mother. Chronic GVHD occurred in 12/17
      patients (70%). All of four female survivals did not show acute and chronic GVHD.
      Day 100 transplantation-related mortality was 14% (3/21). Relapse occurred in two
      patients (9.5%) who underwent allo-PBSCT in stage of non-remission at one and six
      months. After follow-up of 40 (15 - 70) months, 11 patients (52.4%) are still
      disease-free survival. These results suggested that peripheral blood stem cells
      produce a faster hematopoietic recovery and a lower relapse of leukemia. The rate
      of aGVHD is not increased when using the peripheral blood as source of stem
      cells; however, cGVHD continues to be a significant problem. Donors tolerated the
      procurement procedure without complications.

PMID- 14575547
TI  - [Treatment of one case of adult chronic myelogenous leukemia by two units of
      unrelated umbilical cord blood transplantation].
AB  - To explore the hematopoietic reconstitution and transplantation-related
      complications of two units of unrelated umbilical cord blood combined
      transplantation for the treatment of adult hematologic malignancies, one adult
      patient with chronic myelogenous leukemia received two units of unrelated
      umbilical cord blood combined transplantation. The conditioning regimen was
      busulfan and cyclophosphamide (Bu-Cy). GVHD prophylaxis regimen consisted of
      mycophenolate mofetil (MMF), cyclosporine A (CsA) and methotrexate (MTX). The
      patient received total nucleated cells 4.63 x 10(7)/kg with CD34+ cells 8.34 x
      10(5)/kg. Engraftment was documented by the analysis of short tandem repeat with
      polymerase chain reaction (STR-PCR). The results showed that the STR-PCR analysis
      for peripheral blood at day 31, 46 and 71 after transplantation suggested that
      one of two units of cord blood were completely engrafted. The ANC > 0.5 x 10(9)/L
      in the patient occurred at day 23, blood platelet counts > 20 x 10(9)/L at day 33
      and > 50 x 10(9)/L at day 47. The Philadelphia chromosome and bcr/abl fusion gene
      of the patient also turned to negative after engraftment. Acute GVHD grade II
      occurred at day 13 and cured after treatment. It is concluded that umbilical cord
      blood can be used in adult hematopoietic stem cell transplantation. Two or more
      units umbilical cord blood combined transplantation might be the way to solve the
      problem of the low counts of nucleated cells when be used for adult.

PMID- 14575548
TI  - [FasL-cDNA transfected into mouse bone marrow cells ex vivo to prevent graft
      versus host disease].
AB  - To explore the new approach to prevent graft versus host disease (GVHD) by
      purging ex vivo T lymphocytes of bone marrow graft through Fas-FasL way, FasL
      cDNA was transfected into BALB/c mouse bon e marrow cells by liposome ex vivo.
      The transfected cells were cultured together with BAC (BALB/c x C57BL/6) mouse
      bone marrow graft. The mixing bone marrow graft was infused into BALB/c mouse
      recipients after 60Co-gamma irradiation. The mortality, manifestation and
      pathologic change of GVHD in recipient mice were observed. The CFU-S and Y
      chromosome from donor mice were detected. The results showed that compared with
      control group, the mortality in 60 days of the recipients in the experimental
      group decreased (20% vs 70%, P < 0.01) and the morbidity of GVHD lowered (40% vs
      100%, P < 0.01). The CFU-S counts for all groups were at normal level on 20 days
      after transplantation. The Y chromosome from donor mice was discovered in 70%
      bone marrow nucleated cells of recipient mice survived over 2 months in the
      experimental group. It is concluded that mFasL-cDNA transfected mouse bone marrow
      cells prevent GVHD after culturing together with bone marrow graft, and
      accelerate hematopoietic reconstitution in recipient mice.

PMID- 14575549
TI  - [Real-time quantitative PCR detecting minimal residual disease in multiple
      myeloma patients after autologous peripheral blood stem cell transplantation].
AB  - In order to explore the role of real-time PCR in detecting minimal residual
      disease in multiple myeloma and Waldenstrom's macroglobulinemia after autologous
      peripheral blood stem cell transplantation (APBSCT), real-time PCR was used to
      quantitate the IgH rearrangement in 8 patients with multiple myeloma (MM) and 1
      case of Waldenstrom's macroglobulinemia before and after APBSCT. The results
      showed that the copies of IgH rearrangement pre- or post-APBSCT were 3108 +/-
      1043 and 549 +/- 660 (P < 0.05) respectively. The number of IgH copies was
      positively correlated with the amount of plasmocytes in patient 's bone marrow
      and the M-protein in peripheral blood (r = 0.86, P < 0.05). Similar result was
      obtained in a case of relapsed Waldenstrom's macroglobulinemia. In conclusion,
      the quantitative analysis of IgH rearrangement by real-time PCR is a novel way to
      evaluate the therapeutic efficaciousness and predict the prognoses in MM
      patients.

PMID- 14575550
TI  - [Effect of erythrocyte preserved for different lengths of time on anti-D antibody
      identification with three blood matching tests].
AB  - The specificity of the antigens and length of preservation time of erythrocytes
      are the interfering factors in blood group serological tests. In order to clarify
      the influence of preservation time of erythrocytes on the blood matching test,
      the titers of anti-D antibody were detected with papain method, BioVue cross
      matching card and DianaGel cross matching card in 7 series of panel red blood
      cells preserved for various length of time (0 to 9 months). The results showed
      that the titer of micro-column gel test (DianaGel card) was one tube higher than
      that of column agglutinating test (BioVue card). The titer of erythrocytes
      preserved for 9 months was as high as 256 tested by DianaGel card, but it was
      only 2 by papain method in the same anti-serum. It is suggested that there was no
      obvious difference between the results of micro-column gel test and column
      agglutinating test, and titer of papain method was the lowest.

PMID- 14575551
TI  - [Dynamic changes of ultrastructure of erythrocytes in prolonged preservation at 4
      degrees C].
AB  - To study the dynamic changes of ultrastructure of erythrocytes in prolonged
      preservation of blood with preservative fluid containing superoxide dismutase
      (SOD), the whole blood samples were preserved at 4 degrees C in SOD-containing
      solution, the morphologic changes of erythrocyte were dynamically ob served by
      transmission microscopy after preservation for 42, 75 and 85 days, an d the blood
      samples preserved in GMA solution served as control. Three variance was applied
      to analyze the data with SAS software. The results showed that the metamorphotic
      rates of erythrocyte preserved in SOD-containing solution for 42, 75 and 85 days
      were lower than those of erythrocytes preserved in GMA solution. Most of
      metamorphotic rates of erythrocyte preserved in SOD-containing solution for 42,
      75 and 85 days were correspond to those of erythrocytes preserved in GMA solution
      for 42 days, or even lower. It is concluded that SOD-containing preservative
      fluid might help to maintain the normal morphology of erythrocytes in prolonged
      preservation at 4 degrees C.

PMID- 14575552
TI  - [Studies on the blood group serologic characters of enzyme-only red cell
      antibody].
AB  - The objective of this study was to investigate the serologic characters of enzyme
      only red cell antibody and its clinical significance, and to provide basis for
      the safety of blood transfusion. The patient serum containing enzyme-only
      antibody was used to react with the red cells of donors, panel cells and auto
      cells in various medium. Absorption and elution test were also per formed. The
      results showed that this blood sample was found to contain an antibody that
      reacted with donor red cells and panel cells only in papain medium, but was not
      demonstrable by indirect antiglobulin test and other method s. Decline of
      antibody titers was observed after absorption test, but antibody activity was not
      detected in the elute. The patient underwent transfusion with 600 ml of Rh type
      identical RBCs, without any hemolytic transfusion reaction. In conclusion, enzyme
      only antibody usually doe s not lead to hemolytic transfusion reaction.

PMID- 14575553
TI  - [Modification of in situ cryopreservation of human bone marrow mesenchymal stem
      cells].
AB  - The study was aimed to evaluate if the modified in situ cryopreservation could
      affect the biological function of mesenchymal stem cells (MSC) in vitro.
      Mesenchymal stem cells from human bone marrow were isolated by standard method
      and characterized with their morphology, cell-surface antigen profile and
      differentiation repertoire in vitro. The culture-expanded MSC were cryopreserved
      in situ with culture medium (DMEM-LG) containing 10% D MSO and 30% selected FCS
      in -70 degrees C. Following recovery of cryopreservation, differentiation to
      adipocytes, chondrocytes, and osteoblast in vitro and cell cycle analysis were
      performed to investigate whether the cryopreservation would change the
      differentiation potential of MSC. The results showed that after recovery of
      cryopreservation, there was no changes detected as compared with the culture
      expanded MSC in both differentiation potency and growth pattern at 12 weeks. In
      conclusions: this optimized short term in situ cryopreservation at -70 degrees C
      could retain biological characteristics of human MSC for at least 3 months, and
      this method may be useful for cryopreservation of hum an bone marrow MSCs.

PMID- 14575554
TI  - [The application of SCGE-KIAS in monitoring of DNA damage in lymphocytes of tumor
      patients treated with cyclophosphamide].
AB  - Single cell gel electrophoresis assay (SCGE), also named as alkaline comet assay,
      was a simple, rapid and sensitive method to evaluate DNA damage. In this study
      SCGE technique was used to monitor DNA damage difference in tumor patients caused
      by chemotherapy, DNA damage distribution frequency and DNA damage characters were
      analyzed by komet image analysis system (KIAS). The results showed that
      cyclophosphamide greatly caused DNA damage in lymphocytes of tumor patients.
      There was significant difference of peripheral blood lymphocyte DNA damage
      between tumor patients and healthy controls. Tail length of lymphocytes were
      33.69 +/- 7.56 micro m, and tail DNA% we re 31.51 +/- 5.4 6% in 10 cancer
      patients treated with cyclophosphamide, while Tail length were 1 6.2 +/- 1.5
      micro m and tail DNA% were 7.46 +/- 1.15% in healthy controls. there was great
      significant difference on tail length and tail DNA% values between cancer
      patients and healthy controls (P < 0.01). In conclusion, the successful
      measurement of DNA damage caused by Cyclophosphamide treatment means that the
      alkaline comet assay as a valuable tool can be very useful in cancer
      epideminology study, and also be valuable to evaluate DNA damage status of
      patients in clinic.

PMID- 14575555
TI  - [Development of methodology for isolation and culture of mesenchymal stem cells
      derived from mouse skeletal muscle].
AB  - To address the question whether there exists mesenchymal stem cells in adult
      mouse skeletal muscle, mononuclear cells from muscle were obtained by digestion
      and density gradient centrifugation and plated in alpha-MEM/F12 medium containing
      10% fetal bovine serum. Cell biological properties including morphology,
      cytochemistry, growth pattern and phenotypes as well were evaluated. Likewise,
      the osteogenesis of cultured cells was also observed. The results showed that
      adherent cells homogenous in shape proliferated quickly in the culture system.
      The phenotypes of the cells were unique, which were positive for CD29 and Sca-1,
      and negative for CD34 and CD45. Cytochemistry evaluation showed that they were
      homogeneously positive for acid alpha-naphthl acetate esterase (ANAE) and acid
      phosphatase (ACP), and negative for alkaline phosphatase (ALP) and that, around
      5% of them were positive for glycogen (periodic acid-Schiff reaction, PAS). Cells
      became ALP-positive after the induction by ascorbic acid, beta-phosphoglycerol
      and dexamethasone. It is concluded that mesenchymal stem cells exist in murine
      skeletal muscle and compose the complex heterogenous population of stem cells in
      muscle.

PMID- 14575556
TI  - [Alteration of plasma interleukin-18 level in leukemia patients and its clinical
      significance].
AB  - To explore the alteration of plasma level of IL-18 in patients with leukemia
      before and after chemotherapy and its clinical significance, the plasma level of
      IL-18 was determined with ELISA method before and 2 weeks after chemotherapy in
      37 leukemia patients, and 18 normal individuals. The results showed that the
      plasma IL-18 level (153.34 +/- 50.74 pg/ml) in leukemia patients was similar to
      the level (135.82 +/- 47.00 pg/ml) in normal control, and the IL-18 level in ALL
      patients was significantly increased (173.3 +/- 34.4 pg/ml), while the IL-18
      level in CML patients (111.8 +/- 50.5 pg/ml) was lower than normal level. After
      chemotherapy, the IL-18 level (100.89 +/- 50.07 pg/ml) was significantly lower
      than normal level and oneself before treatment. It is concluded that plasma IL-18
      levels in leukemia patients are un-homogeneous and IL-18 production decreased
      after chemotherapy, and immunologic hypofunction in patients with chemotherapy
      might be related with the decrease of IL-18 and related cytokines.

PMID- 14575557
TI  - [Multidrug resistance mediated by membrane P-glycoprotein in acute myeloid
      leukemia].
AB  - A key issue in the treatment of acute leukemia is the development of resistance
      to chemotherapeutic drugs. Several mechanisms may account for this phenomenon,
      including failure of the cell to undergo apoptosis in response to chemotherapy,
      or failure of the drug to reach and/or affect its intracellular target. This
      review focuses on the latter mechanisms, and on intracellular drug transport
      resistance mechanisms in particular. Expression of the ATP-binding cassette (ABC)
      transporter P-glycoprotein (P-gp) has generally been reported to correlate with
      prognosis in acute myeloid leukemia (AML). Additionally, of more controversial,
      expression of the ABC transporter multidrug resistance protein (MRP) and the
      vault-transporter lung resistance protein (LRP) have been correlated with the
      outcome in AML.

PMID- 14575558
TI  - [Progress in the studies of acute myelogenous leukemia stem cell].
AB  - Acute myelogenous leukemia (AML) cells are organized in a hierarchical fashion,
      with only the most primitive rare population (leukemia stem cell, LSC) of AML
      cells capable of maintaining the leukemic clone. A broad range of studies has
      indicated that AML results from mutations at the level of the stem cells of AML
      cells. The changes of cellular and molecular features in these malignant stem
      cells determine the features of leukemic clone and give rise to different
      subtypes of AML. LSCs share some similar characteristics with normal
      hematopoietic stem cells (HSC) including the ability to self-renew, and also have
      the potential of limited differentiation. LSCs, also have some features that are
      not found in normal HSC. LSCs have unique phenotype such as CD90-, CD117- and
      CD123+. Tumor-suppressor protein-death associated protein kinase and interferon
      regulatory factor 1 were overexpressed in LSCs, but not in normal HSC. Due to a
      predominantly G0 cell-cycle status, LSCs may not be responsive to conventional
      chemotherapeutic agents, compared with leukemia blasts. It is proposed that
      surviving LSCs are a major contributing factor to leukemic relapse. Although LSC
      population is likely to be drug-resistant, quiescent LSCs are preferentially
      susceptible to apoptosis induction while sparing normal HSC, with the appropriate
      stimulus such as proteasome inhibitor MG-132. This article reviewed the data
      emerging from the study of LSCs, and elucidated the distinct cellular and
      molecular characteristics of the LSC population, which may shed new light on AML
      therapy and leukemogenesis study.

PMID- 14575559
TI  - [Advance in research on lymphochip technology and its application].
AB  - The lymphochip is a special DNA chip which is used to monitor the gene expression
      profiling of malignant lymphoma. The basic principle, technological procedure and
      types of lymphochip were briefly reviewed in the article. The article
      emphatically introduced the advance of lymphochip implication which was used to
      identify the molecular diagnosis, distinguish the subtypes and research the
      morbific mechanism of malignant lymphoma. The aspects of development and problems
      in lymphochip study were discussed.

PMID- 14575560
TI  - [Mismatch pair defective phenotype in hereditary nonpolyposis colorectal cancer
      in the Chinese].
AB  - OBJECTIVE: To study the protein expression pattern of DNA mismatch repair genes
      hMSH(2), hMLH(1) and the microsatellite instability (MSI) status in the tumor
      tissue from hereditary nonpolyposis colorectal cancer in the Chinese. METHODS:
      Fifty-eight families fulfilling different clinical criteria including Amsterdam
      Criteria (AC) (22/24 families, 38 tumors), Japanese Criteria (JC) (12/15
      families, 16 tumors) and Bethesda Guidelines (BG) (12/19 patients, 13 tumors)
      were studied. Monoclonal antibodies against hMSH(2), hMLH(1) proteins and a panel
      of microsatellite markers (5 loci) including BAT26, BAT25, D2S123, D5S346 and
      D17S250 were used for study. RESULTS: MSI-H was identified in all 22 (100%) AC
      tumors, with 81.8% (18/22) showing altered hMSH(2) or hMLH(1) expression; in
      14/15 (93.8%) JC cancer, 1/1 (100%) JC adenoma, with 45.5% (5/11) showing altered
      hMSH(2) or hMLH(1) expression; and in 7/13 (53.8%) BG tumors, with 4/7 showing
      loss of hMSH(2) or hMLH(1) gene expression. CONCLUSION: The frequency of MSI-H
      and loss of mismatch repair protein are different in the families fulfilling
      different clinical criteria. Amsterdam Criteria and Japanese Criteria are the two
      most useful criterion systems for identifying mismatched repair defective tumors.
      However, Bethesda Guidelines should also be used for detecting more such tumors.
      The combination of immunohistochemical methods and microsatellite instability
      analysis is an effective strategy to detect the mismatch repair defective tumors.
      A close correlation does exist between hMSH(2), hMLH(1) protein expression
      pattern and MSI status.

PMID- 14575561
TI  - [Mdr-1 ribozyme in the reversal of multidrug resistance in human ovarian cancer].
AB  - OBJECTIVE: To study the mechanism of multidrug resistance and its reversal by mdr
      1 ribozyme in human ovarian cancer. METHODS: The expression of mdr-1 and p
      glycoprotein (p-gp) was studied by confocal laser microscope (Confocal), RT-PCR
      and Western blot analysis in adriamycin-resistant human ovarian cancer cell line
      (A2780/ADM) and adriamycin-sensitive one (A2780). The mdr-1 ribozyme was
      transfected into the A2780/ADM by Lipofectamine 2000 to overcome the multidrug
      resistance in ovarian cancer. RESULTS: The expression of mdr-1 mRNA and p-gp in
      A2780/ADM was significantly higher than that in A2780. The expression of mdr-1
      mRNA and p-gp in A2780/ADM was lowered after being transfected by mdr-1 ribozyme.
      CONCLUSION: Multidrug resistance of A2780/ADM, possibly being caused by
      overexpression of mdr-1 gene, can be partially reversed by mdr-1 ribozyme.

PMID- 14575562
TI  - [Celastrol in the inhibition of neovascularization].
AB  - OBJECTIVE: To study the inhibition effect of celastrol on neovascularization.
      METHODS: The effect of celastrol on the in vitro proliferation of endothelial
      cell of vessel (ECV) was examined by MTT assay. The effect of celastrol on
      endothelial cell migration, tube formation on Matrigel and Chick chorioallantoic
      membrane angiogenesis was also examined. Matrigel plug assay was used to evaluate
      the effect of celastrol on angiogenesis in vivo. RESULTS: The proliferation of
      ECV was inhibited significantly by celastrol with IC(50) being 1.33 microg/ml.
      Celastrol inhibited endothelial cell migration and tube formation in a dose
      dependent manner. Celastrol also inhibited angiogenesis both in Matrigel plug of
      mouse model and in chick chorioallantoic membranes. CONCLUSION: Celastrol, which
      can inhibit angiogenesis, could be developed as an antiangiogenic drug.

PMID- 14575563
TI  - [Hepatitis B x protein activated vascular endothelial growth factor expression
      through hypoxia inducible factor-1 pathway].
AB  - OBJECTIVE: To investigate whether hepatitis B x protein (HBx) stimulates vascular
      endothelial growth factor (VEGF) through hypoxia inducible factor-1 (HIF-1 alpha)
      pathway. METHODS: Two plasmids including pIRES-EGFP-HBx and pTK-Hyg were co
      transfected to a hepatocellular carcinoma cell line SMMC-7721. With fluorescence
      positive and fluorescence-negative hygromycin-resistant colonies selected,
      expressions of VEGF and HIF-1 alpha in protein or/and mRNA level were detected.
      RESULTS: Fluorescence-positive cells were stably integrated with HBx, in which
      expression of HIF-1 alpha and VEGF were upregulated. Fluorescence-negative cells
      did not express HBx, VEGF or HIF-1 alpha. CONCLUSION: HBx can activate VEGF
      through HIF-1 alpha pathway.

PMID- 14575564
TI  - [Establishment of malignant progression associated gene expression profiles in
      human brain glioma].
AB  - OBJECTIVE: To establish malignant progression associated gene expression profiles
      in human brain glioma. METHODS: The primary (WHO grade II), recurrent (WHO grade
      III) and re-recurrent (WHO grade IV) glioma specimens were sequentially collected
      from one single patient. Gene expression of different tumor specimens and normal
      brain tissue of the same patient was compared by microarrary techniques. RESULTS:
      197 differentially expressed genes with differential ratio > or = 3 were observed
      when compared with normal brain tissue. When the specimens (3 tumor, 1 normal
      brain) were paired with each other, 7 groups containing 489 genes (upregulated
      193, downregulated 296) were observed. According to the descending frequency of
      the 109 genes with known function, they were the genes associated with
      development, metabolism, differentiation, signal transduction, DNA binding
      transcription, cellular receptor, immunity, ion-channel transportation, protein
      translation, cell backbone motion, stress, protooncogene and anti-oncogene and
      cell apoptosis, respectively. CONCLUSION: From the 197 differentially expressed
      genes found in one glioma patient experiencing tumor malignant progression, 17
      genes screened out by bioinformatics assay, may offer valuable information on
      molecular mechanisms on genesis and malignant progression of glioma.

PMID- 14575565
TI  - [Rac subfamily expression and activity in gastrointestinal cancer cell lines].
AB  - OBJECTIVE: To investigate the significance of Rac subfamily members in the
      gastrointestinal carcinogenesis and progression. METHODS: The mRNA expression of
      Rac1, Rac2 and Rac3 in 12 kinds of gastrointestinal cancer cell lines was
      examined by semi-quantitative RT-PCR. The activities of Rac1 protein in 5 kinds
      of gastric cancer cell lines were tested by pull-down assay. RESULTS: Compared
      with the normal gastric mucosa and intestinal epithelial cell line, the mRNA
      expression of Rac1 and Rac3 was up-regulated in most of gastrointestinal cancer
      cell lines. The activities of Rac1 protein increased markedly in gastric cancer
      cell lines. CONCLUSION: The increased mRNA expression of Rac1 and Rac3 in
      gastrointestinal cancer cell lines and the abnormal activation of Rac1 protein in
      gastric cancer cell lines might be correlated with the carcinogenesis of
      gastrointestinal cancer.

PMID- 14575566
TI  - [In vivo effect of Shu-Gan-Liang-Xue decoction on estrogen].
AB  - OBJECTIVE: To observe the in vivo effect of traditional chinese medicine (TCM)
      Shu-Gan-Liang-Xue (SGLX) decoction on estrogen in vivo in mice. METHODS: Mice
      were randomly divided into control, tamoxifen (TAM), SGLX and SGLX + TAM groups.
      After SGLX decoction had been given to mice for 21 days, the serum hormone level
      of mice was tested by radioimmunological method, uterine weight index was
      obtained by uterine weight divided by body weight. Endometrial change was
      pathologically observed. RESULTS: SGLX decoction reduced the level of serum
      estrogen more than the control with significant difference (P < 0.001). Uterine
      weight index was more lowered in the SGLX group than the control giving a
      difference but not significant. The endometrium in the SGLX group showed no
      change when compared with that of the control, but the SGLX + TAM group showed
      slightly more endometrial hyperplasia than the TAM group. CONCLUSION: SGLX
      decoction, having synergistic effect on TAM, can reduce serum hormone level and
      alleviate the endometrial hypertrophy side effect of TAM.

PMID- 14575567
TI  - [The specific killing of human melanoma cells by replication selective
      adenovirus].
AB  - OBJECTIVE: To construct replication selective adenovirus AdhepE1 targeting human
      melanoma and observe its specific killing of human melanoma cells in vitro.
      METHODS: Adenovirus E1 region, the murine tyrosinase promoter and enhancer DNA
      sequences were acquired respectively by PCR cloning. The shuttle plasmid of
      replication-selective adenovirus targeting human melanoma was constructed by DNA
      recombination. Replication-selective adenovirus AdhepE1 was generated by
      homologous recombination. The human melanoma cell line SK-Mel-1 and
      hepatocellular carcinoma cell line HepG2 were attacked separately by lower dose
      of AdhepE1. Change of cell morphology was observed and the surviving cells were
      calculated. The expression of E1A was assayed by RT-PCR to verify the specific
      replication of AdhepE1. RESULTS: Replication selective adenovirus AdhepE1
      targeting human melanoma was acquired by PCR. Human melanoma cell line SK-Mel-1
      was sensitive to oncolytic killing of AdhepE1 whereas HepG2 was little
      responsive. The results of RT-PCR suggested that AdhepE1 replicated specifically
      in human melanoma cells. CONCLUSION: AdhepE1 can selectively kill human melanoma
      cells.

PMID- 14575568
TI  - [Relation between single nucleotide polymorphism in estrogen-metabolizing genes
      COMT, CYP17 and breast cancer risk among Chinese women].
AB  - OBJECTIVE: To test the hypothesis whether polymorphism in estrogen-metabolizing
      genes, COMT and CYP17, impacts on the risk of breast cancer among Chinese women.
      METHODS: COMT (Val158Met) and CYP17 (T1931C) polymorphisms were detected by PCR
      based restriction fragment length polymorphism analysis in 250 breast cancer
      patients and 250 frequency-matched normal controls. Odds ratios (ORs) and 95%
      confidence intervals (CIs) were estimated by unconditional logistic regression.
      RESULTS: COMT Met/Met genotype was found in 10.4% of breast cancer patients,
      which was significantly higher (P = 0.03) than that in controls (5.2%). Women
      with Met/Met genotype showed 2-fold increased risk for breast cancer (adjusted OR
      2.1, 95% CI 1.1 - 4.5) compared with those with Val/Val or Val/Met genotypes.
      Stratified analysis showed that the elevated risk of breast cancer, associating
      with the COMT Met/Met genotype, was evident only among premenopausal women
      (adjusted OR 4.1, 95% CI 1.2 - 17.3) but not among postmenopausal women (adjusted
      OR 1.3, 95% CI 0.5 - 3.5). There was no significant difference in the
      distribution of CYP17 genotypes between breast cancer patients and the control
      subjects (P = 0.83). CONCLUSION: The allele encoding for low activity COMT, but
      not CYP17, may be a genetic risk factor for breast cancer among Chinese women.

PMID- 14575569
TI  - [Significance of CEA, SCC and Cyfra21-1 serum test in esophageal cancer].
AB  - OBJECTIVE: To study the clinical significance of serum CEA, SCC and Cyfra21-1
      test in the diagnosis, prediction of prognosis and postoperative monitor of
      recurrence in esophageal cancer. METHODS: The concentration of serum CEA and
      Cyfra21-1 was measured by electrochemiluminescence immunoassay (ECLIA) using
      Elecsys 2010, CEA kit and Cyfra21-1 kit. Serum SCC was measured by microparticle
      enzyme immunoassay (MEIA) using IMx System and SCC kit. Serum of 206 patients
      with esophageal cancer (203 squamous cell carcinoma, 2 small cell carcinoma and 1
      adenosquamous carcinoma) was measured preoperatively, 71 of whom also measued 8
      to 12 days after resection. RESULTS: The cut-off value of CEA and Cyfra21-1 was <
      or = 3.25 ng/ml and < or = 2.61 ng/ml, which were determined by the data of 45
      healthy Chinese measured during the same period. The positive ratios of serum CEA
      and Cyfra21-1 in 206 cases were 29.1% and 45.1%. The combined positive ratio of
      CEA and Cyfra21-1 was 57.3%. The CEA positive ratios, according to the
      pathological stage of 165 resectable patients, were 16.6% (stage I), 26.8% (II)
      and 30.8% (III). For Cyfra21-1, they were 27.8%, 37.5% and 50.5%. For CEA
      combined with Cyfra21-1, they were 38.9%, 50.0% and 63.7%. The mean value of CEA,
      SCC and Cyfra21-1 (especially SCC and Cyfra21-1) was found to be well correlated
      with the tumor volume, TNM stage and depth of tumor invasion. Patient with bulky
      tumor or advanced tumor (T4) usually had much higher mean value than those with
      early stage tumors. One week after radical resection, the level of the three
      tumor markers fell to normal level in 92.9% of 71 patients. The level of serum
      CEA and Cyfra21-1 varied greatly in a small part of the patients. Extremely
      elevated serum CEA and Cyfra21-1 usually indicated advanced lesion or tumor
      metastasis. CONCLUSION: Preoperative and postoperative measurement of serum CEA,
      SCC and Cyfra21-1 (especially Cyfra21-1) is helpful in the diagnosis, prediction
      of prognosis and monitor of postoperative recurrence in patients with esophageal
      cancer.

PMID- 14575570
TI  - [Quantitative pathologic technique in prognostic identification of breast
      carcinoma with negative lymph node].
AB  - OBJECTIVE: To study the prognostic identification of lymph node negative breast
      carcinoma by quantitative pathologic technique. METHODS: Several morphometrical
      parameters, DNA content of cell nuclei were detected by means of a quantitative
      pathologic technique on 102 patients with lymph node negative invasive breast
      duct carcinoma. The effects of potential prognostic factors of lymph node
      negative breast cancer patients were assessed by Cox's proportional hazards
      regression model. RESULTS: DNA index, minimal diameter of nuclei, area of nuclei,
      maximal diameter of nuclei, and the perimeter of nuclei are important factors to
      influence the prognosis. CONCLUSION: Quantitative pathologic technique combined
      with valid statistical methods, as an objective means of assessing prognosis, may
      reliably improve the outcome in lymph node negative breast cancer.

PMID- 14575571
TI  - [Preliminary study on gene expression profile of endometrial adenocarcinoma].
AB  - OBJECTIVE: To determine candidate genes of endometrial adenocarcinoma. METHODS:
      To compare the gene expression profile in 2 endometrial adenocarcinoma tissues
      and 2 normal endometria by HGEC-40s GeneChip probe including 4096 genes array.
      Expression differences between normal and malignant tissue groups were measured
      by GenePixPro3.0 software. RESULTS: 350 genes with a ratio below 0.5 and above
      2.0 showed discrimination between normal and malignant groups. Thirty three genes
      with ratio above 3 were up-regulated, forty-four genes with ratio below 0.3 were
      down-regulated. CONCLUSION: The overexpression of oncogenes with their disturbed
      or constitutively activated signal transduction cascades alone or in combination
      with the mutation-induced silencing of tumor suppressor genes is associated with
      malignant transformation.

PMID- 14575572
TI  - [Influence of dendritic cell infiltration on prognosis and biologic
      characteristics of progressing gastric cancer].
AB  - OBJECTIVE: To study the relation between dendritic cell (DC) infiltration and
      clinicopathologic parameters, biologic characteristics and prognosis of
      progressing gastric cancer. METHODS: The development of apoptotic cell death
      (apoptotic index, AI) in 61 progressing gastric carcinoma tissues was analyzed by
      terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin
      nick end labeling (TUNEL) method. The PCNA labeling index (PCNA-LI), density of
      dendritic cells in the tumor were detected by immunohistochemical method by the
      LSAB kit using antibody against S-100 protein and PC-10. RESULTS: DC infiltration
      was negatively correlated with lymph node metastasis, clinical stage and PCNA-LI,
      but positively with AI. The DCs in gastric cancer groups with and without lymph
      node metastasis were (5.63 +/- 4.37)/HPF and (8.51 +/- 5.57)/HPF with difference
      significant (P < 0.05). The DC infiltration in I, II, III stage lesions were
      (11.23 +/- 6.05)/HPF, (6.28 +/- 4.37)/HPF and (5.53 +/- 5.19)/HPF also with
      differences significant (P < 0.01). The PCNA-LI was significantly higher in the
      low DC group (57.10% +/- 14.18%) than that of high DC group (48.15% +/- 10.59%, P
      < 0.01). AI findings were 3.77% +/- 1.26% and 2.95% +/- 1.07% in the high and low
      DC groups (P < 0.01). A positive correlation was observed between DC infiltration
      and AI (r = 0.39, P < 0.01) whereas a negative correlation between DC
      infiltration and PCNA-LI (r = -0.47, P < 0.01). The prognosis of high DC
      infiltration patients was significantly better than those with low ones.
      CONCLUSION: The infiltrating dendritic cells in and around tumor, representing
      the local immune status of the host, may play an important role in immunological
      defense mechanism of host versus tumor. Dendritic cells may inhibit the
      proliferation and induce the apoptosis of the tumor cells, thus affecting the
      clinical features and improve the prognosis of gastric carcinoma.

PMID- 14575573
TI  - [Giant pathologic section in the study of optimal length of surgical resection
      for esophageal carcinoma].
AB  - OBJECTIVE: To study the optimal surgical resection length for esophageal
      carcinoma. METHODS: Specimens of seventy patients with esophageal squamous cell
      carcinoma resected and collected in our hospital were made into pathologic giant
      sections. Direct intramural infiltration, multicentric carcinogenic lesion and
      leaping metastasis were observed in the large slice by microscope. The actual
      length during the operation was calculated by the ratio of shrinkage. RESULTS:
      Direct intramural infiltration was found in 51 (72.9%) patients, 39 proximal and
      36 distal to the tumor. The mean length of direct intramural infiltration was 0.9
      +/- 0.8 cm (4.0 cm maximum) proximally and 0.5 +/- 0.3 cm (2.0 cm maximum)
      distally. Multicentric carcinogenic lesion was found in 11 (15.7%) patients, 5
      proximally, 8 distally and 2 on both sides. Proximal to the tumor, the mean
      distance between the multicentric carcinogenic lesion and the main lesion plus
      the length of the multiple carcinogenic lesion was 3.2 +/- 1.5 cm (4.7 cm
      maximum). Distal to the tumor, it was 3.6 +/- 2.4 cm (9.1 cm maximum). Leaping
      metastasis was found in 9 (12.9%) patients, 7 proximally and 4 distally. The mean
      distance between the leaping metastasis and the main lesion plus the length of
      the leaping metastatic lesion was 1.9 +/- 0.6 cm (2.9 cm maximum) proximally and
      1.4 +/- 1.0 cm (2.7 cm in maximum) distally. CONCLUSION: The optimal surgical
      resection length for esophageal carcinoma should be at least 5 cm proximal to the
      tumor and total length on the distal side.

PMID- 14575574
TI  - [Multivariate analysis of recurrence in T1 bladder transitional cell carcinoma].
AB  - OBJECTIVE: To investigate the prognostic value of some clinicopathologic indexes
      and biologic tumor markers in predicting recurrence in T1 transitional cell
      carcinoma (TCC) of the bladder. METHODS: The expressions of p53, E-cadherin and
      VEGF of 75 patients with T1 primary bladder TCC were detected by streptabitin
      peroxidase (SP) immunohistochemical methods. The effects of clinicopathologic
      indexes and biologic tumor markers on recurrence were assessed by Kaplan-Meier
      and Cox proportional hazards model. RESULTS: The 1-, 3-, and 5-year recurrence-
      free survival rates were 68.0%, 45.3% and 20.9%. In Kaplan-Meier analysis, tumor
      mutifocality and the expression of p53, E-cadherin and VEGF were associated with
      recurrence. In multivariate analysis, the independent recurrence variables were
      tumor mutifocality, the expression of p53 and E-cadherin. CONCLUSION: Tumor
      mutifocality and the abnormal expression of p53 and E-cadherin are the variables
      that independently predict recurrence in T1 transitional cell carcinoma of the
      bladder.

PMID- 14575575
TI  - [Relationship of PTEN, Mdm2 and p53 expression in astrocytoma].
AB  - OBJECTIVE: To study the incidence of PTEN, Mdm2 and p53 expression in different
      histopathological grades of astrocytoma and the signal transduction mechanism
      through which PTEN affects Mdm2 and p53 expression. METHODS: Surgical specimens
      from 68 brain astrocytoma patients were analyzed to detect PTEN, Mdm2 and p53
      expression by immunohistochemical method. RESULTS: The incidence of PTEN, Mdm2
      and p53 expression was 54.4% (37/68), 41.2% (28/68) and 45.6% (31/68). The
      positive incidence of Mdm2 was 24.3% (9/37) in 37 cases with PTEN expression and
      61.3% (19/31) in 31 cases without, which had a negative correlation between Mdm2
      expression and PTEN expression (P < 0.01). Eighteen cases showed Mdm2(+)/p53(+)
      and 27 cases showed Mdm2(-)/p53(-). A significant correlation was found between
      Mdm2 and p53 expression (P < 0.05). CONCLUSION: The histopathological grade of
      astrocytoma is correlated with the loss of PTEN expression, Mdm2 amplification
      and p53 mutation. Mdm2 amplification, being in accordance with p53 mutation, can
      be inhibited by PTEN expression.

PMID- 14575576
TI  - [Primary non-Hodgkin lymphoma in the female genital system: a report of 28
      cases].
AB  - OBJECTIVE: To evaluate the clinical characteristics, results of treatment, and
      prognostic factors of patients diagnosed as having primary female genital system
      lymphoma (PFGSL). METHODS: Twenty-eight cases of PFGSL were retrospectively
      surveyed and the clinical data of the patients were analyzed by statistic
      software package of SPSS10.0 for relation between clinical stage, grade,
      pathologic feature, treatment and prognosis. RESULTS: The median age was 44 in
      the cohort. It mainly involved cervix uterus, ovary and vulva. The disease had a
      broad range of pathologic type and 20 patients were diagnosed as suffering from B
      cell by immunophenotyping, 4 patients were diagnosed as T-cell and 4 patients
      lesions were indefinite. According to International Working Formulation (IWF),
      66.7% belonged to the intermediate-grade. The Ann Arbor stage included: Stage
      I(E)-12 pts (42.86%), Stage II(E)-3 pts (10.7%), Stage III(E)-1 pts (3.6%) and
      Stage IV-12 pts (42.86%). According to International Prognostic Index (IPI), 10
      were low risk, 9 low-medium risk, 3 medium-high risk and 6 high risk, The median
      follow-up of the surviving patients was 2.0 years (range: 3 months-17 years), The
      5-year overall survival rate was 39.3%. Most patients were given comprehensive
      treatment without any mode showing significant advantage over the others in
      survival (P = 0.2554), The involved organs, Ann Arbor stage, IWF and also IPI
      were significant prognostic factors for survival, CONCLUSION: The management of
      PFGSL should be based on comprehensive treatment including chemotherapy as the
      chief means. The significant prognostic factors of survival is Ann Arbor stage,
      IPI, IWF and the kind of involved organs.

PMID- 14575577
TI  - [Type of surgery for 147 patients with medullary carcinoma of the thyroid].
AB  - OBJECTIVE: To study the optimum type of surgical treatment for thyroid medullary
      carcinoma. METHODS: From May 1960 to July 2000, 147 patients with thyroid
      medullary carcinoma were treated with surgical treatment. The results of
      tumorectomy, subtotal and total thyroidectomy were compared. RESULTS: The overall
      5-, 10- and 15-year survival rates were 85.4%, 77.4% and 73.1%. The recurrence
      rate was lowest in the total thyroidectomy group, medium in the subtotal group
      and highest in tumor extirpation group (P < 0.05). The overall cervical lymph
      node metastasis rate was 72.1%. The cervical occult nodal metastasis rate in
      clinically N0 patients was 42.1% (occult metastasis rates in central and lateral
      cervical regions were 24.6% and 36.8%). Thirteen patients with persistent
      postoperative hypercalcitoninemia were observed from 5 months to 6 years without
      tumor recurrence. CONCLUSION: Total thyroidectomy is the optimal treatment for
      thyroid medullary carcinoma. Regardless of clinical N0 or N1, central and
      ipsilateral neck dissection should be considered. Patients with persistent
      postoperative hypercalcitoninemia should be observed closely.

PMID- 14575578
TI  - [Impact of short-term neoadjuvant hormonal treatment on neuroendocrine
      differentiation in prostate carcinoma].
AB  - OBJECTIVE: To study the impact of short-term neoadjuvant hormonal treatment on
      neuroendocrine (NE) differentiation and the relation of NE differentiation and
      tumor regression. METHODS: The radical prostatectomy specimens and the biopsy
      specimens of the same 18 patients with prostate cancer were compared. The effect
      of hormonal treatment on NE-differentiation was evaluated by specific antibodies
      against chromogranin A (ChA) and serotonin (5-HT). RESULTS: The ChA-positive cell
      count was 3.2 x 10(-5)/microm(2) [(0-5.7) x 10(-5)/microm(2)] before hormonal
      treatment and 2.3 x 10(-5) microm(2)[(0-6.6) x 10(-5)/microm(2)] afterward (P >
      0.05). For the proportion of NE-positive tumor, it was 7.0% (0%-14.9%) and 4.5%
      (0%-13.1%) (P > 0.05). No correlation existed between NE-differentiation and the
      neoadjuvant hormonal treatment. The NE cell density did not differ significantly
      between 12 non-/slightly regressive tumor foci and 6 highly regressive ones (P >
      0.05). CONCLUSION: Short-term neoadjuvant hormonal therapy does not induce clonal
      propagation of NE cells. The degree of tumor regression following short-term
      neoadjuvant hormonal therapy is not correlated with the NE differentiation.

PMID- 14575579
TI  - [Anemia in patients on combined androgen block therapy for prostate cancer].
AB  - OBJECTIVE: To study the effect of combined androgen block therapy on hemoglobin
      (Hb) and hematocrit value (Ht) in patients with prostate cancer. METHODS: One
      hundred and thirty-six patients with adenocarcinoma of the prostate were treated
      with combined androgen block (orchiectomy and flutamide 250 mg, Tid). Complete
      blood counts were detected before initiation and after 1, 2, 3, 6, 9 and 12
      months of therapy. RESULTS: Hb level declined significantly in all patients from
      a mean baseline of (136 +/- 14) g/L to (126 +/- 16) g/L, (121 +/- 14) g/L, (120
      +/- 15) g/L, (113 +/- 12) g/L, (121 +/- 13) g/L and (123 +/- 15) g/L at 1, 2, 3,
      6, 9 and 12 months. Ht decreased from a mean baseline of 0.424 +/- 0.041 to 0.390
      +/- 0.038, 0.381 +/- 0.042, 0.378 +/- 0.038, 0.366 +/- 0.041, 0.384 +/- 0.039 and
      0.387 +/- 0.040. The differences between Hb, Ht before and after treatment were
      significant (P < 0.05). CONCLUSION: Patients with prostate cancer being treated
      with combined androgen block would develop a significant degree of anemia.
      Hemoglobin and hematocrit level should be monitored periodically. This kind of
      anemia can be treated by recombinant human erythropoietin.

PMID- 14575580
TI  - [Clinical and pathological features of 23 patients with primary lymphoma of the
      testis].
AB  - OBJECTIVE: To study the clinical and pathological features of primary lymphoma of
      the testis and try to find out the rational treatment modality. METHODS:
      Retrospective and follow-up analysis was conducted in 23 patients with primary
      lymphoma of the testis. Survival analysis was performed by Kaplan-Meier process.
      RESULTS: The primary clinical symptom was painless tumefaction. 78.3% lesions
      were Stage I(E) on diagnosis. Most of them were intermediate grade B cell
      lymphoma. All patients received orchiectomy followed by chemotherapy and some
      followed by radiotherapy. The median survival time was 42 months. The overall
      survival rates at 1, 3 and 5 years were 100.0%, 59.8% and 36.5%, respectively.
      The disease-free survival rates at 1, 3 and 5 years were 66.7%, 42.3% and 36.3%,
      respectively. CONCLUSION: Primary lymphoma of the testis is preferably treated by
      multi-modality treatment. More than 6 cycles of chemotherapy is rational after
      orchiectomy. Regional radiotherapy tends to reduce the local relapse.

PMID- 14575581
TI  - [The management of thyroid well-differentiated carcinoma invading the upper
      aerodigestive tract].
AB  - OBJECTIVE: To investigate the management and prognosis of thyroid well
      differentiated carcinoma invading the upper aerodigestive tract. METHODS: A
      retrospective analysis of the management was performed done 62 patients with
      thyroid well-differentiated carcinoma invading the upper aerodigestive tract. The
      main method of surgery was shaving excision, and the other means including
      partial thyrochondrectomy, total laryngectomy, sleeve tracheal resection,
      sternocleidomastoid myoperiosteal flap and myodermal flap reconstruction, or
      simply palliative excision. Some patients received postoperative radioactive
      isotope therapy and radiotherapy. All patients were followed-up for 2 to 15 years
      with an average of 6.5 years. RESULTS: The best curative effect was proved in the
      patients with local invasion, with the lumen uninvolved and their locoregional
      control rate was 100.0% (17/17). And the second choice was in patients with more
      extensive involvement of the upper aerodigestive tract structures. For them,
      extensive surgical management was done attempting to remove all gross disease
      followed by reconstruction, their locoregional control rate was 87.5% (7/8). And
      the third place was designated to patients with local invasion for which shaving
      excision was performed even though minor residual disease was left, their
      locoregional control rate was 55.6% (5/9). The poorest result went to simple
      palliative excision. For 17 patients with minor residual tumor, the locoregional
      control rate of those who were given postoperative radioactive isotope therapy
      was significantly higher than those without. CONCLUSION: According to the limits
      and degree of invasion in the upper aerodigestive tract by thyroid well
      differentiated carcinoma, different ways of surgery is indicated. For patients
      with residual disease, radioactive isotope therapy should be used to improve the
      result and life quality. Advanced lesions should be given postoperative radio
      therapy.

PMID- 14575582
TI  - [Clinical trial on exemestane in the treatment of postmenopausal women with
      advanced breast cancer].
AB  - OBJECTIVE: To evaluate the response rate and adverse reactions of exemestane (a
      new aromatase inactivator) in the treatment of postmenopausal women with advanced
      breast cancer. METHODS: One hundred and seventy-three patients with advanced
      breast cancer entered this study with two patients excluded because of
      postmenopausal time being less than one year. Therefore, 173 patients could be
      evaluated for adverse events and 171 patients could be evaluated for efficacy.
      Exemestane, 25 mg orally daily for 4 weeks as one cycle was given. RESULTS: In
      the 171 patients evaluated for efficacy, 4 (2.3%) experienced a complete response
      (CR) and 40 (23.4%) a partial response (PR), with the overall response rate of
      25.7%. Ninety patients (52.6%) had stable disease (SD), with 25 having SD for at
      least 24 weeks. The clinical benefit (CR + PR + SD > or = 24 weeks) was shown in
      69 (40.4%) patients. Progressive disease (PD) was shown in 37 (21.6%) patients.
      The untreated patients had a higher objective response rate (33.8%) than the
      retreated ones (18.1%) with significant difference (P = 0.019 7). The response
      rates for soft-tissue, bone involvement and visceral metastasis were 32.8%,
      23.9%, and 12.4% (P = 0.002). There was no significant difference in different
      ages, time of menopause, disease-free interval or receptor status (P > 0.05).
      Drug-related adverse events were gastric discomfort (17.9%), malaise (17.9%),
      nausea (13.9%), hot flushes (11.0%) and dysphoria (5.8%). Other side reactions
      and abnormal laboratory parameters were observed occasionally which were
      irrelevant. CONCLUSION: Exemestane can be used to treat postmenopausal women with
      advanced breast cancer giving only mild adverse reactions which are well
      tolerated.

PMID- 14575583
TI  - [Randomized trial on adjuvant radiotherapy for postoperative breast cancer: a 15
      year experience].
AB  - OBJECTIVE: To evaluate the long term effects of adjuvant radiotherapy for
      postoperative breast cancer. METHODS: From 1985 to 1986, 162 patients with
      operable breast cancer were randomly given adjuvant radiotherapy according to
      clinical stage and involving condition of axillary lymph nodes (LN). The
      radiotherapy group (RG) was irradiated in the supraclavicular area and/or
      internal mammary area to 50 Gy, while the control group (CG) was not. RESULTS:
      The overall 5-, 10- and 15-year survival rates of the RG were 72.0%, 56.1% and
      54.3%, while they were 66.3%, 51.3% and 49.4% in the CG (P > 0.05). Clinical
      stage I-IIIa and positive or negative LN showed no significant difference in the
      two groups. But in patients with LN(+) > or = 4, the 5-, 10- and 15-year survival
      rates of the RG were 55.6%, 38.9% and 37.1%, which were higher than the CG of
      29.0%, 16.1% and 16.1% (P < 0.05). CONCLUSION: Adjuvant radiotherapy can improve
      the prognosis for breast cancer patients with LN(+) > or = 4, but not for LN(-).

PMID- 14575584
TI  - [Prothrombin deficiency resulted from a homozygous Glu29 to Gly mutation in the
      prothrombin gene].
AB  - OBJECTIVE: To investigate the gene mutations in a pedigree with inherited
      prothrombin (FII) deficiency. METHODS: The activated partial thromboplastin time
      (APTT), prothrombin time (PT), FII activity (FII:C) and FII antigen (FII:Ag) test
      were used for phenotype diagnosis. The genomic DNA was extracted from the
      peripheral blood of the propositus. All the 14 exons, intron/exon boundaries and
      the 5' and 3' untranslated regions (UTR) of the prothrombin gene were amplified
      by polymerase chain reaction (PCR). The PCR products were screened by direct
      sequencing and the mutations detected were further confirmed by restricted enzyme
      digestion. One hundred and three healthy blood donors were used as controls.
      RESULTS: The phenotype of the propositus was prothrombin deficiency (type I).
      With reference to the prothrombin nucleotide sequence published by Degen & Dacie,
      three variations were found in the FII gene of the propositus. Among them, the
      novel mutation was a homozygous A601G subtitution in exon 2. CONCLUSION: The
      prothrombin deficiency of the propositus is caused by a homozygous Glu29 to Gly
      mutation in the prothrombin gene.

PMID- 14575585
TI  - [Heparin cofactor II (HCII) activity and antigen assay and their significance in
      thrombotic diseases].
AB  - OBJECTIVE: To study the plasma HCII activity and antigen level variations and
      their relationship with arterial and deep venous thrombotic diseases. METHODS:
      Seventy-five patients with brain infarction (BI), 50 myocardial infarction (MI),
      36 deep venous thromboembolic disease (DVT) and 50 healthy controls were entered
      in this study. Plasma HCII activity was measured with chromogenic substrate
      method and the HCII antigen level by Western blotting assay. Plasma antithrombin
      (AT) activity was detected for the HCII deficiency individuals with DVT using
      chromogenic substrate method. RESULTS: There was no significant difference in the
      mean plasma HCII activity and antigen levels between BI group [(99.97 +/- 21.14)%
      and 0.96 +/- 0.24], MI group [(98.18 +/- 29.35)% and 0.95 +/- 0.20] and healthy
      controls [(96.80 +/- 20.11)% and 0.93 +/- 0.19]. The plasma HCII activity and
      antigen concentrations in patients with DVT [(89.57 +/- 17.12)% and 0.87 +/-
      10.18] tended to be decreased as compared with healthy controls, but they were
      not significant. No significant difference was found for the prevalence of HCII
      deficiency between patient groups and control group. The HCII deficiency
      individuals with DVT had normal AT activity and fibrinogen concentration.
      CONCLUSIONS: Plasma HCII deficiency may not be the risk factor for arterial
      thrombosis in the Han population of Hunan Chinese. It is needed to further
      confirm if decreased plasma HCII is correlated with venous thrombosis.

PMID- 14575586
TI  - [A novel mutation causes congenital factor V deficiency].
AB  - OBJECTIVE: To investigate the gene defect in a hereditary coagulation factor V
      (FV) deficiency family. METHODS: The plasma FV actigen was measured by one-stage
      clotting assay. The FV antigen was assayed by Biotin-Avidin enzyme linked
      immunosorbent assay (BA-ELISA). The full length of exon 1 to exon 25 and the 5'
      untranslated sequence of FV genomic DNA were analyzed by polymerase chain
      reaction (PCR) and direct sequencing of the amplified fragments, meanwhile the
      defect was identified by T/A cloning sequencing. RESULTS: The plasma coagulant
      activity and amount of FV of the proband were marked deficient (1% and 1.54%,
      respectively). DNA sequence analysis for the proband revealed a causative
      mutation in a heterozygous status. It was one base pair deletion in exon 4 at
      nucleotide 675 inherited from her mother. CONCLUSIONS: A novel mutation in the FV
      gene was identified in the proband with congenital FV deficiency. The mutation
      was 675delA in exon 4 resulting in a frameshift and a premature termination
      codon.

PMID- 14575587
TI  - [A preliminary study on the treatment of severe autoimmune disease by autologous
      peripheral CD(34)(+) cell transplantation].
AB  - OBJECTIVE: To evaluate the feasibility of autologous peripheral CD(34)(+) cell
      transplantation for the treatment of severe autoimmune disease. METHODS: Ten
      patients received mobilized and purified CD(34)(+) cells transplantation. The
      mobilization regimen was CTX plus rhG-CSF and the CD(34)(+) cells were selected
      by CliniMACS. (1.98 +/- 0.95) x 10(8) CD(34)(+) cells were obtained. The purity
      of CD(34)(+) cells was (91.4 +/- 10.6)% and the recovering rate was (60.5 +/-
      19.8)%. The conditioning regimens were CTX (200 mg/kg) plus ATG (90 mg/kg) or CTX
      (150 mg/kg) plus TBI (4 - 6 Gy). (2.14 +/- 1.05) x 10(6)/kg CD(34)(+) cells were
      infused. The time of ANC >or= 0.5 x 10(9)/L was 8.6 +/- 2.5 days, and platelet
      >or= 20 x 10(9)/L was 9.0 +/- 5.2 days. After the hematopoietic recovery, the
      levels of CD(3)(+) T cell, CD(19)(+) B cells and CD(16)(+)CD(56)(+) NK cells were
      all below that of pre-transplantation. The main transplant-related complication
      was CMV infection. The transplant-related mortality was 2/10. All patients who
      survived showed improvement of the disease with DAI score decreasing from 17 to 4
      in systemic lupus erythematosus patients, DAS 28 score from 6.4 to 1.8 in
      rheumatoid arthritis patients. CONCLUSION: The result suggests that autologous
      peripheral CD(34)(+) cell transplantation is an alternative choice for the
      treatment of severe autoimmune disease. The short-term outcome is satisfying.

PMID- 14575588
TI  - [Effective and stable in vitro expression of human coagulation factor VIII by
      retrovirus-based plasmid vector coupled with polyamidoamine dendrimer].
AB  - OBJECTIVE: To demonstrate the effectiveness of a retrovirus-based plasmid vector
      coupled with nanometer material-polyamidoamine (PAMAM) dendrimer in stable gene
      expression of FVIII in vitro and to study the cytotoxicity of PAMAM. METHODS: The
      retrovirus-based plasmid vector pLNC-FVIII BD was generated by cloning a B-domain
      deleted (760aa - 1639aa) FVIII cDNA (FVIIIBD cDNA) into retroviral vector pLNCX.
      The complex that contained PAMAM and pLNC-FVIII BD transfer FVIII BD cDNA into
      NIH3T3 cell line. In day 2, 5, 10, 15, 30 after transferring, the antigen and
      procoagulant activity of human FVIII in the cell culture medium were measured by
      ELISA assay and one-stage method, respectively. RT-PCR was performed for the
      detection of FVIII BD mRNA. Inhibitory percentage of cell vitality was used for
      cytotoxicity of PAMAM. RESULTS: Human FVIII was expressed for 30 days by
      transfected cells. The mean procoagulant activity of secreted FVIII in these 30
      days was 0.929 U/ml, and the FVIII antigen was 0.188 micro g/ml by 10(6) cells in
      24 hours, respectively. The level of FVIII didn't significantly decreased during
      these days. Inhibitory percent of cell vitality was only 5.32%. CONCLUSION: PAMAM
      could effectively transfer pLNC-FVIII BD into NIH3T3 cells and FVIII could be
      stably and effectively expressed by the transfected cells. Cytotoxicity of PAMAM
      was low.

PMID- 14575589
TI  - [Effect of platelet factor 4 on the adherence of cord blood CD34(+) cells].
AB  - OBJECTIVE: To investigate the effects of platelet factor 4 (PF4) on the
      adherence, and the expressions of adherent molecules CD(49d) and CXCR4 and the
      receptor of SDF-1 of fresh and expanded cord blood CD(34)(+) cells. METHODS:
      CD(34)(+) cells were isolated from cord blood using MACS immune magnetic beads.
      The adherent ability was assayed by using crystal violet staining and the
      expression of adherent molecule CD(49d) and CXCR4 by FACS. RESULTS: (1) PF4 could
      increase the adherent ability of the fresh cord blood CD(34)(+) cells, the effect
      being positively correlated with the dose of PF4. (2) SDF-1 at concentration of
      100 ng/ml increased the adherent ability of the fresh cord blood CD(34)(+) cells.
      (3) The spontaneous and the SDF-1 induced adherent ability of the cord blood
      CD(34)(+) cells began to decrease after being cultured for 10 days without PF4,
      while in the presence of PF4 at 100 ng/ml, the ability of the cord blood
      CD(34)(+) cell adhering to the stroma layer still remained at higher level. At
      day 14, the adherent ability was (262.04 +/- 64.81)% and (64.35 +/- 8.29)% in PF4
      group and control group, respectively, if it was defined as 100% at day 0. SDF-1
      at concentration of 100 ng/ml induced adherent ability was (138.31 +/- 32.39)%
      and (67.66 +/- 12.44)% in PF4 group and control group, respectively. (4) The
      expression of CD(49d) and CXCR4 increased 13.02% and 17.33%, respectively, when
      incubated with PF4. CONCLUSIONS: PF4 could increase the adherent ability and
      promote the expression of CD(49d) and CXCR4 of the cord blood CD(34)(+) cells,
      suggesting that PF4 promote the circulating stem cells homing to the marrow in
      the process of stem cells transplantation.

PMID- 14575590
TI  - [Effect of angiotensin II on tissue factor expression in human peripheral blood
      monocytes and its mechanisms].
AB  - OBJECTIVE: To elucidate the effect of angiotensin II (AngII) on the expression of
      tissue factor (TF) by monocytes and its mechanisms. METHODS: Monocytes were
      isolated from healthy volunteers by Ficoll-Hypaque gradient and Percoll, and
      cultured in RPMI-1640. Procoagulant activity (PCA) was determined by one-stage
      clotting method, TF antigen by ELISA. Reverse transcriptase-polymerase chain
      reaction (RT-PCR) was used to detect the TF gene mRNA. The levels of IkappaBalpha
      was detected by Western blot. Electrophoretic mobility shift assays (EMSA) were
      performed to evaluate the activity of NF-kappaB. RESULTS: AngII (10(-9) - 10(-7)
      mol/L) significantly increased monocyte PCA, TF antigen and TF mRNA expression in
      a dose and time dependent manner. Losartan (10(-6) - 10(-5) mol/L) significantly
      inhibited the effects of AngII on TF activity, antigen and mRNA expression in a
      dose-dependent effects. Staurosporine (2.5 x 10(-7) mol/L) and genistein (4 x 10(
      5) mol/L) lowered TF level of monocytes (P < 0.05). Western blot analysis
      revealed that after exposure to AngII (10(-7) mol/L), IkappaBalpha level
      decreased at 15 min, reached nadir at 60 min, and recovered at 180 min. EMSA
      showed NF-kappaB binding activity increased at 15 min, reached peak at 60 min,
      and recovered at 180 min. Pyrrolidine dithiocarbamate (PDTC, 10(-4) mol/L), an
      inhibitor of NF-kappaB, or AT1R antagonist losartan (10(-5)mol/L) inhibited AngII
      induced NF-kappaB translocation. CONCLUSIONS: AngII could induce the expression
      of TF in human monocytes, and this effect was mediated by AT1R. The PKC pathway
      played the most important role in AngII-induced TF expression. The activation of
      NF-kappaB was involved in TF expression in monocytes.

PMID- 14575591
TI  - [Expression of costimulatory molecules on peripheral blood lymphocytes of
      patients with idiopathic thrombocytopenic purpura].
AB  - OBJECTIVE: To investigate the expressions of costimulators on peripheral T and B
      lymphocytes in patients with idiopathic thrombocytopenic purpura (ITP). METHODS:
      The expression of B7-CD(28) and CD(40) of peripheral lymphocytes was measured by
      flow cytometry in 21 ITP patients and 9 normal subjects. The expression of PAIgG
      was measured by ELISA method. RESULTS: The expression of CD(4)(+)CD(28)(+) was
      lower in ITP patients than in normal controls, but the expression of CD(86)(+)
      and CD(86)(+)CD(19)(+) was higher in ITP patients than in normal controls, while
      the expression of CD(80)(+), CD(40)(+), CD(28)(+), CD(19)(+)CD(86)(+),
      CD(19)(+)CD(40)(+), CD(4)(+)CD(28)(+)/CD(4)(+), CD(19)(+)CD(80)(+)/CD(19)(+) and
      CD(19)(+)CD(40)(+)/CD(19)(+) in ITP patients was normal. The PAIgG level was
      higher in 16 patients with a mean of (184.62 +/- 38.00) ng/10(7) plt. A positive
      correlation was found between PAIgG and CD(19)(+)CD(86)(+)/CD(19)(+) expression.
      CONCLUSION: There is no deficiency in expression of CD(28) on CD(4)(+) T
      lymphocytes in ITP patients. The change of CD(86) expression on B lymphocytes is
      possibly involved in pathophysiology of ITP, which may provide a theoretical
      instruction for ITP patients immunological therapy.

PMID- 14575592
TI  - [Study on autoimmune thrombocytopenic purpura related antibody].
AB  - OBJECTIVE: To investigate a specific and sensitive assay for the diagnosis of
      autoimmune thrombocytopenic purpura (AITP). METHODS: Glycoprotein specific
      autoantibodies in platelet eluate and plasma were detected by a modified
      monoclonal antibody immobilization of platelet antigens assay (MAIPA). RESULTS:
      The overall positive rate of specific autoantibodies against platelet GPIIb/IIIa
      and GPIb/IX in plasma was 38.89% and in eluated platelet membrane was 68.52%. The
      difference between them was significant (corrected chi(2) = 19.39, P < 0.005).
      The proportion of positive MAIPA results between primary AITP and secondary AITP
      was not significantly different. There was a significant inverse correlation
      between antibody level and platelet count. CONCLUSION: Detection of eluated GP
      specific autoantibodies by MAIPA is highly specific and much more sensitive as
      compared with the measurement of their plasma counterparts in the diagnosing and
      therapeutic monitoring of AITP.

PMID- 14575593
TI  - [Molecular biological study of glycoprotein IX gene defect in Bernard-Soulier
      syndrome].
AB  - OBJECTIVE: To identify a mutation G2113-->A in the glycoprotein (GP)IX gene
      associated with Bernard-Soulier syndrome (BSS) and to investigate BSS
      pathogenesis. METHODS: Allele-specific restriction enzyme was used to analyze the
      samples of patient, her mother, her brother and 40 healthy volunteers. Site
      directed mutagenesis was performed to construct a expression vector PD-IXG2113A
      harboring the mutation G2113-->A. Chinese hamster ovary (CHO) cells were
      transiently cotransfected with plasmids harboring the entire coding region of
      GPIbalpha, GPIbeta and GPIX or mutant GPIX, respectively. Expression of GPIbalpha
      and GPIX in transfected CHO cells were analysed with flow cytometer. GPIbalpha
      and GPIX in the cytoplasma of transfected CHO cells were analysed by
      immunostaining and Western blotting. RESULTS: The patient was found to be
      homozygosity of the substitution, her mother and her brother be heterozygous.
      Expressions of GPIbalpha and GPIX in mutant CHO cells were remarkably reduced,
      but abundant in the cytoplasma. CONCLUSION: The mutation of Ala139(GCC)-
      >Thr(ACC) in the GPIX did not affect synthesis and assembly of GPIb/IX complex
      but influence its anchoring and expression on the cell surface, which was
      responsible for BSS.

PMID- 14575594
TI  - [The preliminary study on in vitro differentiation of human umbilical cord blood
      cells into neural cells].
AB  - OBJECTIVE: To explore the feasibility of in vitro differentiation of human
      umbilical cord blood cells (HUCBC) into neural cells induced by receptor
      activator of NF-KappaB ligand (RANKL) and brain-derived neurotrophic factor
      (BDNF). METHODS: Normal fresh HUCBC were cultured as the following: (1) Control
      group cultured by differentiation medium only; (2) BDNF group, cultured by
      differentiation medium + BDNF; (3) RANKL group, cultured by differentiation
      medium + human soluble RANKL (sRANKL); (4) BDNF + RANKL group, cultured by
      differentiation medium + BDNF and sRANKL. Cultured cells were observed with
      invert microscope. After ten-days culture, the expression of glial fibrillary
      acidic protein (GFAP) and neuron-specific nuclear protein (NeuN) of the cultured
      cells were detected by immunocytochemical staining. RESULTS: After 10 day's
      culture, the NeuN positive cells were (97.0 +/- 13.5), (85.0 +/- 5.6), (167.0 +/-
      19.7) in RANKL, BDNF and BDNF + RANKL groups, respectively, with 1.7, 1.5, 3.0
      fold in crease than that of control (55.7 +/- 8.5), the GFAP positive cells were
      (114.7 +/- 18.0), (233.3 +/- 21.7), (289.0 +/- 24.7), respectively, with 1.4,
      2.9, 3.6 fold increase compared with the control group. The differentiation ratio
      of neurons in RANKL group was similar to that of the BDNF group, but the
      differentiation ratio of glial cells was lower than that in the BDNF group. In
      the RANKL + BDNF group, the differentiation of HUCBC into neurons and glial cells
      were enhanced obviously, the differentiated neural cells were typical with longer
      axons and dendrites. CONCLUSION: RANKL and BDNF could induce HUCBC into neurons
      and glial cells, and they have synergistic effect on the induced differentiation.
      It is hopeful that HUCBC might be an source of stem cells for the treatment of
      central nervous system injury.

PMID- 14575595
TI  - [A case-crossover study of ambient air pollution and daily mortality in
      Shanghai].
AB  - OBJECTIVE: Using case-crossover design to estimate the acute effect of ambient
      air pollution on daily mortality in Shanghai, and to explore the applicability of
      if in studying the acute health effects of air pollution. METHODS: Case-crossover
      technique was used to evaluate the relationship between air pollution and daily
      mortality from June 2000 to December 2001 in Shanghai. The results of the bi
      directional control sampling approach were compared with unidirectional approach.
      RESULTS: The validity of relative risks in case-crossover studies varied greatly
      depending on the strategy used in control sampling. When a bi-directional six
      control sampling approach was used an increase of relative risk of non-accident
      mortality on each 10 micro g/m(3) over a 48-hr moving average of PM(10), SO(2)
      and NO(2) corresponds to 1.003 (95% CI: 1.001 - 1.005), 1.016 (95% CI: 1.011 -
      1.021), and 1.020 (95% CI: 1.012 - 1.027) respectively was seen. CONCLUSION: The
      results reinforced the deleterious role of current air pollution level on human
      health in Shanghai, and provided information on the applicability of case
      crossover design in studying the acute health effects of air pollution.

PMID- 14575596
TI  - [Blood lead level and related risk factors among children aged 0-6 years in
      Beijing].
AB  - OBJECTIVE: To observe blood lead level and related risk factors among children of
      0 - 6-year old in Beijing. METHODS: Stratified-clustered-random sampling and
      simple random sampling were used. A total of 2 262 children of 0 - 6 years old
      were investigated from May to July 2001. They were permanent residents in
      Beijing. Blood lead level was tested by graphite atomizer absorption
      spectrophotometer. At the same time, related factors were investigated using a
      standardized questionnaire. RESULTS: The mean lead level of children in Beijing
      was 96.8 micro g/L with 35.7% of those >/= 100 micro g/L, and 2.5% >/= 200 micro
      g/L. The proportion of lead poisoning was significantly higher in rural children
      (P < 0.01). The proportion of lead poisoning in 2-year-old group was higher than
      that in other age groups. The proportion of lead poisoning in boys was
      significantly higher than that in girls (P < 0.01). The following factors might
      serve as major risk factors related to child lead poisoning, such as, never or
      rarely drinking milk, living in nearby highways (less than 50 meters) or living
      in the first floor/bungalow, and so on. CONCLUSION: The blood lead level of >/=
      100 micro g/L among Beijing children appeared to be a big problem. Decision
      makers should pay more attention to prevent blood lead level being high, and to
      cure these children who suffered in lead poisoning. Effective intervention
      measures on these target populations should be taken.

PMID- 14575597
TI  - [Study on serum p53 protein in cops in Guangzhou city].
AB  - OBJECTIVE: Serum p53 protein overexpression was detected in population exposed to
      traffic exhaust gas to study the relation between traffic exhaust gas and the
      increased risk in p53 gene mutation. METHODS: Serum p53 protein expression was
      measured by enzyme-linked immunosorbent assay. Relationship between different
      types of job and serum p53 protein overexpression were studied by pearson Chi
      square tests. RESULTS: Results on serum p53 protein overexpression on jobs
      outside of office (5.74%) were not significantly higher than jobs inside the
      office. However, it suggested that traffic police men (12.12%) working outside of
      office, with whose length of service longer than 30 years had a significant
      overexpression of serum p53 protein than the others (5.36%) whose length of
      service was less than 30 years (P < 0.05, OR = 2.43, 95% CI: 1.11 - 5.33).
      Overexpression rate of p53 protein appeared to be 6.89% in the group whose
      average weekly exposure hours were more than 40 hours, which was significant
      higher than the group whose exposed hours were less than 40 hours (P < 0.05, OR =
      1.71, 95% CI: 1.03 - 2.81). CONCLUSION: The result suggested that traffic exhaust
      gas was likely to cause mutation of p53 gene and increasing the incidence of lung
      cancer.

PMID- 14575598
TI  - [A case-control study for assessing the relation between the incidence of
      malignant lymphomas and environmental factors in Sichuan province].
AB  - OBJECTIVE: To evaluate the relationships of malignant lymphoma (ML) and exposure
      factors, including environmental, drug using, socioeconomic level and life style
      etc. METHODS: (1) Hospital-based case-control study with 1:2 matching was used;
      (2) 150 cases of ML and 300 controls were resulted; (3) logistic regression was
      used. RESULTS: (1) Adjust odds ratios (aOR) regarding contact to organic solvents
      were: benzene aOR = 2.78, P = 0.001;banana oil aOR = 2.28, P = 0.043; paint aOR =
      1.96, P = 0.023; (2) aOR on pesticides contact: organic phosphorus aOR = 1.98, P
      = 0.034; chrysanthester aOR = 2.57, P = 0.013; organic nitride aOR = 2.55, P =
      0.003; (3) aOR of using aspirin was 2.36, P = 0.005; (4) dog-raising: aOR = 1.76,
      P = 0.034; (5) the aORs of interval-term exposure to small dosage X-ray was 0.49,
      P = 0.015, and frequently catching cold was 0.67, P = 0.024; (6) the P-value of
      different occupations was more than 0.05; cigarette smoking OR = 1.01, P = 0.897;
      giving up smoking OR = 1.17, P = 0.073; alcohol-drinking aOR = 1.01, P = 0.414;
      hair-dyes OR = 1.06, P = 0.850; hair-perms OR = 1.26, P = 0.438; socioeconomic
      level OR = 1.00, P = 1.000 and with introversive character OR = 1.26, P = 0.266.
      CONCLUSIONS: (1) Factors that might increase the risk of suffering from malignant
      lymphomas would include direct contact to organic solvents and some pesticides
      (organic phosphorus, chrysanthester and organic nitride), intake of aspirin, as
      well as dog-raising. (2) Regular exposure to small dosage X-ray and frequently
      catching cold seemed to decrease the risk of suffering from ML. (3) Occupation,
      smoking, giving up smoking, alcohol-drinking, hair-dyes, hair-perms,
      socioeconomic level and introversive character showed no significant relations to
      the risk of suffering from ML in this study.

PMID- 14575599
TI  - [A case-control study on the risk factors of leukemia in mining areas of rare
      earth in South Jiangxi].
AB  - OBJECTIVE: In order to explore the correlation on radioactive contamination of
      lanthanon to leukemia, and provide clues for the causes and prevention of
      leukemia in mining areas of rare-earth elements. METHODS: 1:1 matched case
      control study was used. A total of 51 clinically confirmed leukemia cases,
      individually matched with controls from general population, were interviewed in
      mining areas of rare-earth in South Jiangxi from November to December, 2001. Data
      were analyzed, using conditional logistic regression. RESULTS: The main risk
      factors would include frequently drinking water from river (OR = 5.543), distance
      from residence to rare-earth mine and years for living in the area (OR = 3.308),
      exposure to organophosphorus pesticide (OR = 3.014). Tea drinking habit appeared
      to be a protective factor. CONCLUSIONS: Leukemia seemed to be related to
      environmental pollution with rare-earth elements around the residential areas and
      organophosphorus pesticide exposure. The protective factor of tea drinking habit
      seemed to be unique in this study, which called for further studies.

PMID- 14575600
TI  - [The epidemic situation of human rabies from 1984 to 2002 and its preventive
      measures in China].
AB  - OBJECTIVE: To summarize and analyze the epidemic situation of human rabies from
      1984 to 2002 in China, and to explore the possible factors causing the increase
      of cases so as to provide evidence for preventive and control measures. METHOD:
      National and some provincial data on the prevalence of rabies during 1984 to 2002
      were collected and analyzed. RESULTS: From 1984 to 1989, the annual reported
      cases were between 4 000 and 6 000 but decreased after 1990. In 1996, the
      reported cases decreased to the lowest level from 3 520 in 1990 to 159. However,
      number of reported cases has been continuously increasing since 1998 which
      reached 1 122 in 2002, a 7.06 times increase as compared to the number in 1996.
      The epidemic areas were mainly located in the southeast and southwest parts of
      the country, such as Sichuan, Hunan, Guangxi, Guangdong, Anhui, Fujian, etc.
      Furthermore, there was no significant seasonal distribution as it showed before.
      CONCLUSION: Such facts as the increasing numbers of dogs, low inoculation rate to
      dogs, poor control on the quality of rabies vaccine, mistreatment to the wounds,
      and lacking good cooperation between different official departments regarding
      rabies control might serve as important factors responsible for the recurrence of
      rabies. Therefore, it is necessary to focus on the above mentioned points and to
      take comprehensive preventive measures to bring down the prevalence of rabies in
      China.

PMID- 14575601
TI  - [Evaluation on the accuracy of reported suicides in the Chinese population].
AB  - OBJECTIVE: To evaluate the accuracy of reports of suicide in the national death
      registry systems and to estimate a more accurate suicide rate. METHODS: Twenty
      three sites from the Disease Surveillance Points Network-one of the national
      death registry systems-were selected and 1 932 of the deaths that occurred at
      these sites from August 1995 through August 2000 in which the official cause was
      classified as "accidental" or "mental illness" were selected for detailed
      household surveys focusing on reassessing the cause of death. Valid interviews
      were completed in 1 653 of these cases. The original cause of death recorded on
      the death certificate was compared with the finding of the detailed household
      survey and the result was used to adjust the suicide rate. RESULTS: After
      detailed investigation, 16 of the 857 (1.87%) deaths reported on the death
      certificate as suicide were considered accidental deaths, 39 of the 721 (5.41%)
      accidental deaths were considered suicide, 17 of the 35 (48.57%) cases reported
      as undetermined accidents were considered suicide, and 6 of the 40 (15.00%) cases
      in which mental illness was the recorded cause of death were considered suicide.
      After adjustments for errors in the reported cause of death and for missing
      deaths, the reported crude suicide rate of 13.65/100 000 in China was adjusted to
      22.99/100 000 (95% CI: 21.78/100 000 - 24.25/100 000). CONCLUSION: After
      adjustments the actual suicide rate for China was higher than the reported rate
      indicating that suicide was an increasingly important public health problem for
      China.

PMID- 14575602
TI  - [Study on the occurrence of cesarean section (CS) and factors related to CS in
      China].
AB  - OBJECTIVE: To find out the occurrence of cesarean section (CS) and to probe the
      factors associated with CS. METHODS: Women with CS as "case group" and women
      without CS as "control group" were chosen in a case-control study. RESULTS: Among
      14 071 childbirth women, 6 421 had CS (case group) with the occurrence rate of
      45.6% and 7 650 (54.4%) had normal delivery (control group). In comparison with
      the control group, the CS group had following several higher rates [with
      significant differences between case group and control group (P < 0.01)]: well
      educated (78.9% vs 69.5%), white collar jobs (38.0% vs 32.3%), urban residents
      (79.1% vs 70.6%), high monthly income (>/= 500 Yuan) (81.0% vs 70.6%), of older
      age (>/= 25 years) (73.3% vs 63.0%), heavier baby weight (> 4 000 gram) (8.3% vs
      2.9%), male babies (53.9% vs 51.4%), BMI of mother (> 24) (8.8% vs 4.8%),
      cephalopelvic disproportion (21.1% vs 0.9%), intrauterine asphysia (20.3% vs
      6.7%), abnormality of force of labor (4.2% vs 2.7%), prolonged labor (2.9% vs
      1.0%) and placenta previa (1.4% vs 0.4%). Our study also indicated that the
      higher the educational level was, the higher the rate of CS appeared; and the
      older the pregnant women was, the higher the rate of CS was. In CS group, over
      70% primipara were over 24 years, and over 20% primipara had cephalopelvic
      disproportion and over 20% had intrauterine asphysia in CS group. CONCLUSIONS: At
      present, the occurrence rate of cesarean section was rather high (45.6%) in
      China. The high rate of CS was more likely to associate not only with abnormal
      physiological/medical factors (eg. cephalopelvic disproportion, intrauterine
      asphysia, abnormality of force of labor, and prolonged labour, etc.), but also
      with some demographic factors as education, occupation, income and age, etc. It
      is necessary to take measures to reduce the unnecessary CS in China.

PMID- 14575603
TI  - [Analyses on the effect of community-based intervention on hypertension].
AB  - OBJECTIVE: To testify the feasibility of management through contract system
      between general practitioners and patients. METHODS: In Sichuan province contract
      was made between general practitioners and hypertension patients in "community
      health service center-family of hypertension patients" in Yulin community in
      Chengdu city. After half a year, we analysed the effects of community-based
      intervention on hypertension. RESULTS: General means of both SBP and DBP
      remarkably decreased (P < 0.05) with SBP remarkably decreased by 8.94 mm Hg while
      DBP decreased by 3.61 mm Hg. After interfered by the model, people whose blood
      pressure were above normal had a remarkable decrease than before by 14.06 mm Hg
      (P < 0.05). Rates of hypertension being under control increased from 38.39% to
      64.29% (P < 0.001). Rates of awareness on fatness and heredity in hypertensive
      patients were increasing from 58.06% to 74.19% (P < 0.001). Rate of awareness on
      risk factors for hypertension was also higher than that of 6 months back (P <
      0.05). CONCLUSION: The model of management by signing contract between general
      practitioners and patients in community, proved to be a successful way in the
      treatment to control high blood pressure.

PMID- 14575604
TI  - [Reliability and validity of a 7-day physical activity questionnaire for
      elementary students].
AB  - OBJECTIVE: To evaluate the use of a 7-day physical activity questionnaire in
      epidemiologic studies on 4-6th grades children. METHODS: Focus group discussion,
      observation and expert consultation were used to develop 7-day physical activity
      questionnaire. The reliability and validity of questionnaire were determined in a
      sample of 92 children in 4-6th grades who were randomly selected from four
      schools in urban Beijing. A two-week test-retest reliability was determined. The
      questionnaire was validated against experts' evaluation and Caltrac motion
      sensor. RESULTS: For different measures of activity, the agreement was good
      between the test and retest. Kappa values ranged from 0.46 to 0.79, and the
      Spearman correlations ranged from 0.66 to 0.87 in boys and 0.57 to 0.82 in girls,
      with significant difference (P < 0.01). The face validity and content validity
      were good by experts' evaluation. There was no significant difference between
      questionnaire results and Caltrac motion sensor for both boys and girls, and the
      questionnaire correlated significantly (r = 0.46, 0.38 for different measures of
      activity) with Caltrac motion sensor for boys. CONCLUSION: These data provided
      evidence that the 7-day physical activity questionnaire yield a reliable estimate
      of past week physical activity for 4 - 6-grade children and provided valid
      estimation of past week physical activity for boys.

PMID- 14575605
TI  - [Study on the characteristics of incidence and death among inpatients with injury
      in Guangdong province from 1997 to 2001].
AB  - OBJECTIVE: To study the trends in the distribution and change of total injuries
      were explored during 1997 - 2001. To provide scientific bases in setting up
      priorities and improving safety standards. METHODS: To collect and analyze the
      data about all inpatients of injuries attending hospital and hospitalization at
      322 hospitals between 1997 and 2001 in Guangdong, China. The main outcome
      measures included external causes, medical consequences, mortality, length of
      hospital stay, and costs. RESULTS: Rate of all-injury hospitalization increased
      yearly, from 1997 to 2001. The ratio of inpatient case-fatality declined over a 5
      year period, with the total case-fatality rate of 1.64%. The inpatients were
      mainly caused by motor vehicle accident, unintentional falls, punctured and cut
      by machine, hurt by others and homicide. The constituent ratio of deaths among
      patients caused by motor vehicle accident was accounted for 56.13% among the
      total deaths, which occupied the first place. Despite the fact that the mean
      length of stay declined by 3.58% for the hospitalized patients over a 5 year
      period, and by 2.20% for the healed patients, costs increased by 3.89% for the
      hospitalized patients and by 4.71% for the healed patients with an average costs
      per patient per day increased by 7.33%. CONCLUSION: The all-injury
      hospitalization rate had a trend of increase from 1997 to 2001, but the ratio of
      inpatient case-fatality declined over the 5-year period, and the direct medical
      cost also had a trend of increase.

PMID- 14575606
TI  - [Effects of a comprehensive health education program on reproductive tract
      infections/sexually transmitted diseases intervention among reproductive age
      population in the rural areas of China].
AB  - OBJECTIVE: To evaluate the effectiveness on comprehensive health education
      intervention program regarding reproductive tract infections/sexually transmitted
      diseases (RTIs/STDs) among reproductive age population in the rural areas of
      China. METHODS: Data were generated from the Reproductive Health/Family Planning
      Project implemented by the State Family Planning Committee and the Ministry of
      Health from 1998 to 2002, which covered 32 counties in 22 provinces. A quasi
      experimental design was used. Six counties were selected from 32 project counties
      as intervention group, while 6 non-project counties were taken as controls which
      were similar in number of population and economic level to the counties as
      selected. Subjects of the study were mothers with children under 3 years and men
      under 35 years of age. A total number of 675 mothers and men were interviewed
      using a structured questionnaire by strictly trained investigators. Logistic
      model was used to compare the difference of knowledge on RTIs/STDs between
      intervention group and control group. OR value was used to describe the degree of
      the difference. RESULTS: Over the 18 month intervention period, persons in the
      intervention group had more knowledge of RTIs/STDs than those in control group.
      Logistic regression analysis indicated that intervention was significantly
      associated with better knowledge on factors as transmission, risks, symptoms,
      management and prevention of RTIs/STDs with 95% CI of OR as 2.4 - 6.4, 2.0 - 4.8,
      3.0 - 6.4, 1.9 - 5.7 and 1.8 - 6.8 respectively, after controlling the
      demographic factors. Level of education was an important factor influencing the
      subjects to receive knowledge on RTIs/STDs. CONCLUSION: Comprehensive health
      education intervention programs had significant impact on knowledge about
      RTIs/STDs among the target population, indicating that the Reproductive
      Health/Family Planning Project implemented in the rural areas of China had been
      successful.

PMID- 14575607
TI  - [Establishment of consensus sequence of PreS/S of hepatitis B virus with genotype
      B/serotype adw2 or genotype C/serotype adrq+ prevailing in Chongqing of China].
AB  - OBJECTIVE: To develop consensus sequence of HBV PreS/S with different subtype in
      Chongqing of China. METHODS: The gene of PreS/S of HBV in 18 AsC was sequenced.
      The genotype and serotype of HBV were determined. The main HBV strain prevailing
      in Chongqing was identified to establish its consensus sequence. RESULTS: It was
      found that 9 strains were genotype B/serotype adw2, 6 were genotype C/serotype
      adrq+ and 3 were genotype B/serotype ayw1. The consensus sequence of PreS/S of
      HBV with genotype B/serotype adw2 and genotype C/serotype adrq+ were established.
      There were 6 nucleotide variants which causing 4 amino acids change between
      consensus sequence of PreS/S with genotype B/serotype adw2 in Chongqing and in
      Southeast of China (homology showed 99.5% and 99.0% respectively). There were 13
      different sites that caused 4 amino acids change between consensus sequence of
      PreS/S with genotype C/serotype adrq+ in Chongqing and in Northeast and South of
      China (homology showed 98.9% and 99.0% respectively). Comparing the two consensus
      sequence of PreS/S gene of different subtype HBV in Chongqing, there was 95
      variants which caused 40 amino acids variants (the homology was 92.1% and 90.0%
      respectively). CONCLUSION: The consensus sequence of PreS/S of hepatitis B virus
      with genotype B/serotype adw2 and genotype C/serotype adrq+ prevailing in
      Chongqing was established.

PMID- 14575608
TI  - [Recombinant OspC identification and antigenicity detection from Borrelia
      burgdorferi PD91 in China].
AB  - OBJECTIVE: To recombine OspC gene from Borrelia burgdorferi PD91 of China and
      expressed it in E. coli for early diagnosis of Lyme disease. METHODS: The OspC
      gene was amplified from the genome of Borrelia burgdorferi PD91 strain by
      polymerase chain reaction and recombined with plasmid PET-11D. The recombinant
      plasmid PET-11D-OspC was identified with PCR, restriction endonuclease analysis
      and sequencing. The antigenicity was verified with Western Blot. RESULTS: OspC
      gene was cloned correctly into vector PET-11D. The resultant sequence was
      definitely different from the published sequence. The recombinant OspC seemed to
      have had strong antigenicity. CONCLUSION: The findings laid basis for the studies
      on early diagnosis of Lyme disease.

PMID- 14575609
TI  - [Expression of telomerase reverse transcriptase in premalignant esophageal
      squamous dysplasia].
AB  - OBJECTIVE: To study the relationship of human telomerase reverse transcriptase
      (hTRT) and malignant transformation of esophageal dysplasia. METHODS: Telomerase
      activity and hTRT expression in esophageal dysplasia (n = 47), squamous cell
      carcinoma (n = 29) and normal esophagus (n = 11) were detected by telomeric
      repeat amplification protocol (TRAP) and in situ hybridization, respectively.
      RESULTS: Telomerase activity was detected in none of the 11 cases of normal
      esophageal tissues (0%) but in 21 of 47 cases (44.7%) of dysplasia, and in 25 of
      29 cases (86.2%) of esophageal squamous cell carcinoma. There were statistically
      significant differences among the telomerase activity in normal esophagus,
      esophageal dysplasia, and in squamous cell carcinoma (chi(2) = 5.89, P < 0.05;
      chi(2) = 11.35, P < 0.01). hTRT mRNA was expressed in none of the 11 cases of
      normal esophageal tissues (0%) but in 23 of 47 cases (48.9%) of dysplasia, and in
      24 of 29 cases (82.8%) of esophageal squamous cell carcinoma. There were
      statistically significant differences among the expression of hTRT mRNA in normal
      esophagus, esophageal dysplasia, and in squamous cell carcinoma (chi(2) = 6.99, P
      < 0.01; chi(2) = 7.32, P < 0.01). Significant correlation was found between the
      telomerase activity and the expression of hTRT mRNA (chi(2) = 57.91, P < 0.001).
      CONCLUSION: The mRNA expression of hTRT which paralleled to telomerase activity
      implied that there was a crucial role to play in regulating the activation of
      telomerase, and was closely related to the malignant transformation of esophageal
      dysplasia. hTRT might serve as a new, valuable biomarker to detect esophageal
      squamous cell carcinoma.

PMID- 14575610
TI  - [Study on the correlation between the different papillomavirus type and
      telomerase in cervical cancer].
AB  - OBJECTIVE: To define a correlation between different human papillomavirus (HPV)
      types and telomerase activity in cervical cancer. METHODS: Telomerase activity
      was detected by TRAP-PCR, and different HPV type was determined by PCR in 83
      cervical cancer, 47 cervical intraepithelial neoplasia (CIN) and 10 normal cervix
      cases. RESULTS: With regard to positive rates of telomerase and HPV 16/18: the
      results were cervical cancer > CIN > normal cervix, CIN III > CIN I, II; with
      regard to HPV 6/11 positive rate: the results showed CIN I, II > CIN III.
      Positive rates of telomerase cervical cancer and HPV were bearing on grading and
      staging, but they did not correlate with histologic subtypes. Positive rate of
      HPV 6/11 had nothing to do with grading, staging and histologic patterns. On
      expression strength of telomerase and HPV 16/18: the results showed cervical
      cancer > CIN, CIN III > CIN I, II. Regard to HPV 6/11'expression strength: the
      results showed CIN I, II > CIN III, CIN > cervical carcinoma. CONCLUSION: HPV
      16/18 infection seemed to have played an important role in carcinogenesis of
      cervical lesions by activation of telomerase.

PMID- 14575611
TI  - [Psychological status and its influencing factors on patients undergoing
      electrophysiology studies and radiofrequency catheter ablation].
AB  - OBJECTIVE: To study the psychological status and its influencing factors in
      patients before and after electrophysiology studies and radiofrequency catheter
      ablation (RFCA). METHODS: 125 inpatients (71 men, 54 women, mean age 42.91 years
      +/- 16.1 years) who underwent a scheduled electrophysiology studies and RFCA for
      the first time and fulfilled entry criteria, were enrolled. They were randomly
      assigned to receiving either a consent which did not detail specific risk (group
      B) regarding the procedure or one that detailed the risks (group A). All patients
      were examined by the Chinese version of Symptom Check List-90 (SCL-90) within 24
      hours before the procedure (after the consent) and on the third day after.
      RESULTS: (1) Before the electrophysiology studies and RFCA, scores of anxiety and
      phobic anxiety constructs were higher than the norm. After the procedure, no
      specific construct score became higher. (2) After the procedure, patients showed
      a significantly decrease in the scores of obsessive-compulsive, depression,
      anxiety, hostility, phobic anxiety, paranoid ideation, psychotism constructs,
      global severity index, total positive symptoms and positive symptom severity
      index. (3) Women scored higher on somatization, depression, anxiety, phobic
      anxiety constructs, global severity index and positive symptom total before the
      procedure. (4) Detail informed consent was not associated with increased mental
      symptoms when compared with consent that did not detail specific risks.
      CONCLUSIONS: In this study, patients showed slightly anxiety and phobic anxiety
      before electrophysiology studies and RFCA with women having more mental symptoms
      before the procedure that called for special attention. Detail information
      including the course and specific risk regarding the procedure was not associated
      with increased psychological symptoms. It was suggested that the patients should
      receive detail information before electrophysiology studies and RFCA.

PMID- 14575612
TI  - [Study on the risk factors of 100 cases with vulvar dystrophy].
AB  - OBJECTIVE: To assess the risk factors for vulvar dystrophy. METHODS: An
      epidemiological study was carried out. Data on 100 cases with vulvar dystrophy
      was reviewed and face to face interviewed with a uniform questionnaire including
      the manner of work, environmental temperature, habit of eating, mood, underwear
      wearing, autoimmune diseases, marriage, menstrual age, the quantity of menses,
      orders of pregnancy, and labor trauma of vulvar during delivery, vulvitis and
      urethritis ect. Univariable analysis and multivariate logistic regression
      analysis were carried out with 1:1 case-control methodology. RESULTS: Multiple
      conditional logistic regression analysis showed that vulvar dystrophy was
      positively associated with hot food (OR = 2.55, 95% CI: 1.24 - 5.25), mood (OR =
      4.27, 95% CI: 1.96 - 9.29), order of pregnancy (OR = 3.37, 95% CI: 2.11 - 5.40),
      vulvitis (OR = 6.74, 95% CI: 2.66 - 17.09) and urethritis (OR = 11.02, 95% CI:
      1.01 - 120.19). Vulviitis or urethritis increased 6.74 or 11.02 times the
      incidence of vulva dystrophy. Anger or nervous state contributed to the incidence
      of vulva dystrophy (OR = 4.27). Addict to hot food and order of labor also
      increased risk ratio for 2.55 and 3.37 times, respectively. CONCLUSION: The risk
      factors of vulvar dystrophy were: addict to hot food, often holding a angry or
      nervous state, increase of labors, having vulvitis and urethritis.

PMID- 14575613
TI  - [Statistical test on multivariate in therapeutical equivalence analysis].
AB  - OBJECTIVE: To explore the way for testing of multivariate in therapeutical
      equivalence. METHODS: By improved Hotelling T(2) test, the mean vector of two
      groups was tested. The information of each variable could then be obtained by
      deducting the their correlations. "Clinical Equivalence of Drug A and Drug B for
      Postmenopausal Bone Looseness" was used in this research. The primary measure of
      efficacy was regarded as the improvement rate of four variables with predefined
      limit of equivalence (2%) with the results of univariate test and multivariate
      test compared. RESULTS: Under P > alpha, all the variables were nonequivalent.
      Under P </= alpha, it was necessary to filtrate the variables of unequivalent
      until the residuals were equivalent. The method of multivariate test was a remedy
      to the shortage of univariate test. CONCLUSION: With the combination of the
      filtration of nonequivalent variables and the improved Hotelling T(2) test, the
      test of multivariate could be done. The method is reasonable and practical.

PMID- 14575614
TI  - [Bone metabolism in adolescent girls with short course of anorexia nervosa].
AB  - OBJECTIVE: The objective of this study was to determine the prevalence of bone
      mass reduction and determine its causes in young girls with short course of
      anorexia nervosa (AN). METHOD: Bone mineral density (BMD)of lumber spine by dual
      energy x-ray absorptiometry, total alkaline phosphatase (TAP), bone-Gla protein
      (BGP), urine deoxypyridinoline (DPYR), DPYR, urine calcium, sex hormones were
      measured in 24 in-patient girls with diagnosed AN and 20 healthy volunteers.
      RESULTS: Girls with AN had a significantly lower BMD than their age-matched
      controls. Osteopenia and osteoporosis were present even in the group with AN
      diagnosed within the previous 12 months. BMD correlated negatively with minimal
      BMI and positively with the duration of regular menses before AN onset. BGP and
      DPYR were significantly lower in AN patient than in the control group. Values of
      urine calcium of AN patients were comparable with control group, but showed a
      positive correlation with disease duration. DISCUSSION: Reduction of bone mineral
      density is present in girls with short course of AN. Nutritional status is the
      most important predictor of BMD. Bone metabolism is decreased in the early stages
      of the disease.

PMID- 14575615
TI  - [The relationship between insulin-dependent diabetes mellitus and acute
      infections in children].
AB  - The morbidity of insulin-dependent diabetes mellitus (IDDM) in children develops
      not evenly. Epidemiological leaps are periodically registered. This character of
      dynamics suggests the existence of environmental factors having the influence on
      the IDDM morbidity. One of these environmental factors is viral infection. We
      have set ourselves as an object to analyze the relationship between the primary
      morbidity of IDDM and some infectious diseases in children, to build up the
      prognostic models for the dynamics of IDDM morbidity and to evaluate their
      quality. Statistic analysis of the relationship between the primary morbidity of
      chicken pox, scarlet fever, measles, mumps, viral hepatitis, acute intestinal
      infectious diseases (AIID), acute upper respiratory infections (AURI) and insulin
      dependent diabetes mellitus in children of Grodno region covering the period from
      1980 to 2001 years has been performed. It has been established, that morbidity
      rate of IDDM reliably positively correlated with morbidity of AURJ and AIID
      (accordingly r=0.62; and p=0.02 and r=0.46; p=0.04) and negatively with the
      scarlet fever and mumps morbidity (accordingly r=-0.55; p=0.008 and r=-0.53;
      p=0.01). But cluster analysis has shown, that really only indices of AURI and
      AIID morbidity were connected and formed one cluster. Morbidity rate of IDDM in
      children in the current year is most closely connected with AURI and AIID
      frequency in the previous year, but frequency of the above-mentioned infections
      registered in the same year influences less on diabetes morbidity, not mentioning
      the infections of 2-years standing which practically have no influence. If the
      increase in AURI morbidity accounts for 10% as compared to the previous year one
      may prognosticate with high reliability an increase of primary morbidity of IDDM
      by 7.7% on the average during the same year, and by 8.3% in the following year.
      For AIID these indices account for 3.5% and 4.4% correspondingly. In the increase
      of the morbidity rate of AIID the morbidity rate of IDDM reduces.

PMID- 14575616
TI  - [Epidemiology of type 1 diabetes mellitus in Bydgoszcz region in the years 1997
      2002].
AB  - INTRODUCTION: Type 1 diabetes mellitus belongs to the diseases most often
      appearing in the developmental age. The incidence of this disease is
      characterized by the constant dynamic increase. AIM: The purpose of this work was
      to estimate the value and the dynamics of the incidence of type 1 diabetes
      mellitus in children from Bydgoszcz region and its analysis according to sex,
      age, place of residence and season of diabetes diagnosis. MATERIAL AND METHODS:
      In the period from 1997 to 2002 type 1 diabetes mellitus was recognized in 161
      children (80 boys and 81 girls) up to the 14th age of life in separate age
      groups: 0-4 years: 20; 5-9 years: 68; 10-14 years: 73. The incidence was
      estimated with the help of an index which was the number of new-recognized type 1
      diabetes mellitus cases during one year in the population of 100 000. The number
      of population was taken from Demographic Yearbook of Provincial Office. RESULTS:
      The average annual index of the incidence for the six-year period being analyzed
      was 13.55, it balanced in the following years from 9.44 (1997) up to 15.28
      (2002). The highest index of incidence (16.34) was noted in 2000 year. The
      increase in number of falling ill was observed in groups: 5-9 years old and 10-14
      years old. Rarely the diabetes was recognized in the youngest children. The
      diabetes was almost twice more often recognized in children living in towns
      (16.30) in comparison with those living in the country (8.84). Revelation of the
      diabetes takes place mainly in the autumn and winter months. The least number of
      falling ill was noted in June. The seasonal incidence was observed mainly in
      children over 5 years. CONCLUSIONS: 1. The index of the type 1 diabetes mellitus
      incidence among 0-14 year old children was 13.55. 2. During the years 1997-2002
      this index increased from 9.44 to 15.28. 3. The diabetes was almost twice more
      often recognized in children living in towns. 4. The number of becoming ill
      depends on the season of the year.

PMID- 14575617
TI  - [Analysis of type 1 diabetes mellitus symptoms at admission to hospital].
AB  - AIM: The aim of study was analysis of type 1 diabetes mellitus symptoms at
      admission to hospital. MATERIAL AND METHODS: Thirty-seven patients (21 boys and
      16 girls) aged from 1.87 to 19.75 years with admitting diagnosis of diabetes
      mellitus in the year 2000 (the greatest count of patients) were analyzed. In
      statistical analysis the t-Student test was used. RESULTS: The most frequent
      symptoms was dry sensation in mouth 95% of patients, polydypsia 84%, polyuria
      65%, lose on weight 49%, nocturia - 27% children. Nine children were admitted to
      hospital in serious ketoacidosis. Twenty-eight children were admitted to hospital
      in good condition. There were not essential abnormalities in the blood.
      Observation period in poor general condition group was shortest for children
      living in the country - on the average 9 days versus patient from cities - 18
      days. There was not difference in good general condition group. HbA1c, pH, HCO3
      values were statistically significant. In 3 cases diagnosis of diabetes mellitus
      was preceded by an eliminating others diseases. In 2 children hyperglycemia was
      established by chance. CONCLUSION: 1) Ketoacidosis symptoms and serious state was
      observed in 1/4 patient admitted to hospital. 2) It is necessary to take diabetes
      mellitus into consideration more often in differentiation in pediatric practice.
      3) Short observation period of severe ketoacidosis symptoms in-patient from
      country origin and dismiss preliminary diagnosis may indicate insufficient
      healthy education - especially in the field of diabetes mellitus. 4) Less than
      half of patients report to family doctors.

PMID- 14575618
TI  - [Is overweight in patients with type 1 diabetes in the puberty a problem?].
AB  - AIM OF THE STUDY was the appreciation of the body mass index (BMI) of adolescents
      with diabetes type 1 treated with different methods of insulin therapy as well as
      the correlation of the BMI with the age of the patients, duration of the diabetes
      therapy and with the metabolic control. MATERIAL AND METHODS: The examinations
      included 205 patients aged 14 to 18 years (X 16.8). The examined group consisted
      of 112 girls (54.5%) and 93 boys (45.5%). In all the patients the body mass index
      (BMI) was calculated HbA1c, total cholesterol, HDL, LDL, triglyceride the
      duration and method of therapy of diabetes were determined. The patients were
      divided in 4 groups. Group 1 and 3 included patients treated with insulin in
      multiple daily doses (4-5 doses). Group 1 included 49 girls, group 3-36 boys. In
      group 2 and 4 there were patients treated with intensive therapy with insulin
      analogs (Humalog, NOVO Rapid) and NPH insulin. In group 2 there were 63 girls, in
      group 4 -57 boys. RESULTS: In the groups of boys higher statistically significant
      levels of HbA1c were observed in those treated with multiple daily doses (gr. 3),
      the body mass index was higher in boys treated with insulin analogs (gr. 4)
      [p<0.05, vs p<0.05]. CONCLUSIONS: 1. The therapy of diabetes type 1 in the
      puberty with multiple daily doses as well as with the intensive method is not a
      risk factor for obesity. 2. Normal weight evidenced a proper diabetic metabolic
      control and a good education about the rational diet and optimal insulin dose. 3.
      In patients in whom BMI is over normal range it is urgently necessary to verify
      of the therapeutical management. 4. In patients with diabetes type 1 a strict
      control of body mass index and the growth velocity during each visit in the out
      patients is necessary.

PMID- 14575619
TI  - [The role of skeletal muscle in the regulation of glucose homeostasis].
AB  - Muscle tissue has been considered to be a major regulator of systemic glucose
      homeostasis. Glucose normally provides energy sources for tissues of the body.
      Its uptake by muscle requires a secretion of insulin. The initial step of glucose
      utilization requires the transport of glucose into the cells. The insulin
      receptor complex stimulates the cellular uptake of glucose. In the well-fed state
      muscle contains about 1% of its weight as glycogen. Because of its mass, muscle
      contains almost four times as much glycogen as the liver. Muscle glycogen is not
      directly available as a source of blood glucose because muscle lacks glucose-6
      phosphatase. During muscular activity, glycogen is converted to lactate and then
      into blood glucose in the liver.

PMID- 14575620
TI  - [Vitamin D3 overdosage due to rashly diagnosed rachitis in a child with distal
      tubular acidosis].
AB  - Metabolic acidoses are diseases causing many diagnostic and therapeutic problems.
      Compensated metabolic acidosis can be unrecognised for a long time. This refers
      especially to isolated renal tubular acidosis (RTA). Unrecognised RTA causes
      calcium and phosphorus balance disturbances with clinical signs of improper bone
      mineralization. It happens that some patients with mentioned problems are
      "treated" as rachitic and take high doses of vitamin D. As a result, serum
      calcium and phosphates as well as urine calcium increase, without the satisfied
      influence on bone mineralization. We present a case of a 3.5 months old baby, who
      was "treated" as ricket in vitamin D deficiency. This baby was "cured" with high
      doses of cholecalciferol (0.0875 mg/24h for 2 weeks, then 0.175 mg/24h for 3
      weeks) because of craniotabes. This treatment was carried on without any
      metabolic tests and caused the following disturbances: 25(OH)D serum level -
      102.7 ng/ml (normal 11-54), 1,25(OH)2D serum level - 39.5 pg/ml (normal 15-70),
      calcaemia 2.7-2.85 mmol/l, phosphataemia 2.1 mmol/l. In this time the
      considerable hipercalciuria (second morning urine sample Ca/cr ratio 2.06
      mmol/mmol) occurred. The other laboratory test showed as follows: serum albumins
      4.5 g/dl, alkaline phosphatase 188 U/l, acid phosphatase 10.7 U l, Cl- 114.9
      mmol/l, Na 146 mmol/l, K 4.8 mmol/l, HCO3a 16.6-20.1 mmol/l and pCO2 3.63-3.85
      kPa, serum anion gap 11 mEq/l; pH of morning urine 6.5-7. These results suggested
      the presence of distal RTA aside from symptoms of vitamin D overdosage. The high
      serum levels of calcium and phosphates, craniotabes, rather low serum alkaline
      phosphatase activity and presence of metabolic acidosis the symptoms after the
      normalisation of calcium and phosphorus balance suggested that the distal RTA had
      been prior to calcium disturbances.

PMID- 14575621
TI  - Potential Role of Neuroprotective Agents in the Treatment of Patients with Acute
      Ischemic Stroke.
AB  - Currently, intravenous recombinant tissue plasminogen activator is the only US
      Food and Drug Administration-approved therapy for acute ischemic stroke. Although
      efficacious, its usefulness is limited, mainly because of the very limited time
      window for its administration. Neuroprotective treatments are therapies that
      block the cellular, biochemical, and metabolic elaboration of injury during or
      after exposure to ischemia, and have a potential role in ameliorating brain
      injury in patients with acute ischemic stroke. More than 50 neuroprotective
      agents have reached randomized human clinical trials in focal ischemic stroke,
      but none have been unequivocally proven efficacious, despite successful preceding
      animal studies. The failed neuroprotective trials of the past have greatly
      increased understanding of the fundamental biology of ischemic brain injury and
      have laid a strong foundation for future advance. Moreover, the recent favorable
      results of human clinical trials of hypothermia in human cardiac arrest and
      global brain ischemia have validated the general concept of neuroprotection for
      ischemic brain injury. Recent innovations in strategies of preclinical drug
      development and clinical trial design that rectify past defects hold great
      promise for neuroprotective investigation, including novel approaches to
      accelerating time to initiation of experimental treatment, use of outcome
      measures sensitive to treatment effects, and trial testing of combination
      therapies rather than single agents alone. Although no neuroprotective agent is
      of proven benefit for focal ischemic stroke, several currently available
      interventions have shown promising results in preliminary trials and may be
      considered for cautious, off-label use in acute stroke, including hypothermia,
      magnesium sulfate, citicoline, albumin, and erythropoietin. Overall, the
      prospects for safe and effective neuroprotective therapies to improve stroke
      outcome remain promising.

PMID- 14575623
TI  - Sleep-disordered Breathing in Heart Failure.
AB  - Sleep-related breathing disorders are common in heart failure patients and can
      have significant adverse impact on clinical outcomes. If sleep-disordered
      breathing or considerable daytime sleepiness exists, assessment and treatment
      recommendations include the following: 1) carefully assess and correct
      hemodynamic status; heart failure exacerbations can induce central sleep apneas;
      2) if overweight, encourage patient weight loss; 3) elevate head of bed; 4)
      discourage sleeping on back; 5) order polysomnography, to assess type and extent
      of sleep-related breathing disorder; and 6) treat sleep-disordered breathing with
      nasal continuous positive airway pressure or bilevel positive airway pressure.

PMID- 14575622
TI  - Neurogenic Cardiac Injury.
AB  - Cardiac injury may occur following many types of brain injury, although the most
      widely investigated form of neurocardiogenic injury is subarachnoid hemorrhage
      (SAH). Echocardiography may help prognosticate and aid in the treatment of SAH if
      left ventricular (LV) dysfunction is suspected or if troponin levels are
      elevated. Cardiac catheterization, however, is not routinely recommended in SAH
      patients with LV dysfunction and elevated troponin. The priority should be
      treatment of the underlying neurological condition, even in the setting of LV
      dysfunction. Cardiac injury that occurs following an SAH appears to be
      reversible. For patients that develop brain death cardiac evaluation under
      optimal conditions may help increase the donor pool.

PMID- 14575624
TI  - Low Gradient, Low Ejection Fraction Aortic Stenosis.
AB  - Low gradient aortic stenosis can be caused by critical aortic stenosis causing
      left ventricular impairment or by more moderate aortic stenosis coexisting with
      another cause of left ventricular impairment. The main challenges are to
      differentiate these two states and then to determine whether the left ventricle
      is likely to recover after aortic valve surgery. Exhaustive echocardiography is
      necessary, including the use of dobutamine stress. Guideline criteria for severe
      aortic stenosis are given in this article. The most secure criteria are mean
      transaortic pressure difference greater than 30 mm Hg and effective orifice area
      less than 1.2 cm(2) during dobutamine stress. However, the presence of left
      ventricular contractile reserve more closely determines outcome after surgery
      than do markers of stenosis. Surgery is most clearly indicated if there is severe
      aortic stenosis and an increase in the systolic velocity integral by greater than
      20% during dobutamine infusion. Preoperative catheterization is necessary to
      determine coronary anatomy, but the aortic valve should not be crossed because of
      the relatively high risk of death, stroke, pulmonary edema, and cardiogenic
      shock. In patients judged too ill for immediate surgery, a period of medical
      resuscitation with diuretics and dobutamine should be considered. Balloon
      valvotomy is not indicated.

PMID- 14575625
TI  - Beta-adrenergic Receptor Blockers in Heart Failure.
AB  - Congestive heart failure is a progressive disease with high morbidity and
      mortality if left untreated. Standard therapy for patients with systolic left
      ventricular dysfunction now includes angiotensin-converting enzyme inhibitors and
      beta blockers. beta Blockers have been demonstrated to decrease mortality, reduce
      hospitalizations, improve functional class, decrease left ventricular dimensions,
      and improve ejection fraction in several large-scale, randomized, placebo
      controlled trials. In addition to reducing deaths due to progressive heart
      failure, beta blockers also reduce the incidence of sudden death. Therapy with
      beta blockers can successfully be initiated in most patients with heart failure
      if recommended titration schedules are followed. beta Blockers are an important
      component of medical therapy for all stages of heart failure.

PMID- 14575626
TI  - Contemporary Medical, Surgical, and Device Therapies for End-stage Heart Failure.
AB  - Despite recent advances in medical therapy, mortality remains high following the
      diagnosis of heart failure (HF). Cardiac transplantation is still the standard
      surgical treatment option for highly selected patients with severe end-stage HF;
      however, it is only available to a small percentage of patients. The small number
      of available donor hearts is an inherent limitation on the ability of cardiac
      transplantation to greatly impact the management of advanced HF. The increased
      incidence and prevalence of HF in an ever aging and medically complex population
      has paved the way for alternative surgical and device treatment strategies. Some
      of these treatment options include ventricular reduction/remodeling surgery,
      mitral valve repair, mechanical ventricular assist device implantation,
      implantable cardioverter-defibrillators, and cardiac resynchronization therapy.
      Several recent trials have demonstrated the effectiveness of these therapies with
      regard to improvement in primary cardiac end points, HF symptoms, and survival.
      Surgical and device techniques are usually combined with optimal medical
      management of HF. The total cost and actual cost-effectiveness of employing these
      new therapeutic modalities in a growing population of HF patients remains to be
      determined.

PMID- 14575627
TI  - Atherosclerotic Carotid Artery Occlusion.
AB  - Patients with acute stroke caused by atherosclerotic carotid artery occlusion
      (ACAO) should receive intravenous tissue plasminogen activator if they meet
      eligibility criteria. Patients with acute stroke caused by ACAO who are not
      eligible for intravenous tissue plasminogen activator should receive aspirin.
      Heparin or heparin-like drugs do not improve outcome and should not be used.
      Therapy for prevention of recurrent stroke in patients with ACAO should consist
      of lifestyle modifications, risk factor intervention, and aspirin. Other
      antiplatelet drugs should be considered in patients with contraindication to
      aspirin. Warfarin is not indicated. Extracranial-intracranial bypass surgery
      provides no benefit over medical therapy in preventing recurrent stroke in a
      general population of patients with ACAO or in any subgroups selected by clinical
      or arteriographic criteria. Extracranial-intracranial bypass surgery in patients
      selected by hemodynamic criteria should only be performed as part of a randomized
      controlled clinical trial. Other surgical or endovascular procedures have no
      proven value in treating or preventing stroke caused by ACAO. Asymptomatic
      carotid occlusion has a benign prognosis, and requires no specific treatment
      other than lifestyle modification and risk factor intervention.

PMID- 14575628
TI  - Management of Chronic Aortic Regurgitation.
AB  - Aortic regurgitation may be the most treacherous of the valvular lesions due to
      subtlety of symptoms and physical findings and due to difficulty in timing
      surgical intervention to prevent permanent cardiac dysfunction. Cardiac imaging
      (eg, echocardiography or magnetic resonance) is critical to quantify the degree
      of regurgitation and to detect significant left ventricular dysfunction or
      dilation. Stress testing can be useful in timing surgical intervention in
      borderline cases. Medical therapy consists of afterload reduction, diuresis, and
      inotrope administration. Surgical therapy today consists of aortic valve repair
      in a minority of cases or aortic valve replacement in the remainder. Percutaneous
      means to replace the aortic valve are in development. Cardiac decompensation may
      require cardiac transplantation.

PMID- 14575629
TI  - Prospective multicenter study on immediate rehabilitation of edentulous lower
      jaws according to the Branemark Novum protocol.
AB  - BACKGROUND: During recent years a new treatment concept, Branemark Novum, has
      been developed in which implants are inserted in the edentulous lower jaw and
      immediately connected to a prefabricated titanium bar. A fixed prosthesis is then
      attached to the bar during or immediately following surgery. PURPOSE: The aim of
      the present study was to investigate the application of this concept under
      various settings, to determine technique sensitivity, and to evaluate the
      clinical outcome after 1 year of follow-up. MATERIALS AND METHODS: Fifty-one
      patients were included in a prospective multicenter investigation and followed up
      for 1 year. Cumulative implant survival rates were evaluated by life table
      analysis. In addition, clinical comparisons were performed to evaluate implant
      loss in relation to patient characteristics. Questionnaires were used to evaluate
      the treatment protocols and to obtain patients' opinions. RESULTS: The prosthetic
      treatment was completed on the same or the following day in 76% of the patients.
      The cumulative implant survival rates for implants and prostheses were 91% and
      94%, respectively, after 12 months. CONCLUSIONS: The present study demonstrated
      that single-stage surgery and immediate loading of implants with prefabricated
      bridgework in the mandible can result in high implant success and significant
      reduction in treatment time, with patient satisfaction.

PMID- 14575631
TI  - Ramus or chin grafts for maxillary sinus inlay and local onlay augmentation:
      comparison of donor site morbidity and complications.
AB  - BACKGROUND: The placement of endosseous implants in edentulous areas is
      frequently limited by inadequate bone volume of the residual ridge. Local bone
      grafts from the mandible are a convenient source of autogenous bone for alveolar
      reconstruction prior to implant placement. PURPOSE: The aim of the present study
      was to document and compare the morbidity and the frequency of complications
      occurring at two intraoral donor sites: the mandibular symphysis and the
      mandibular ramus. MATERIAL AND METHODS: This study reviewed 53 consecutively
      treated patients: 29 with autogenous bone grafts from the mandibular symphysis
      and 24 with mandibular ramus bone grafts. Each patient received a questionnaire
      18 months after surgery regarding problems that may have occurred during the
      postoperative period. RESULTS: In the patients in whom bone was harvested from
      the mandibular ramus, there were fewer postoperative symptoms immediately after
      the operation than with mandibular symphysis harvesting. Twenty-two of the 29
      patients with symphysis grafts experienced decreased sensitivity in the skin
      innervated by the mental nerve 1 month after the operation. Five of the 24
      patients with ramus grafts experienced decreased sensitivity in the vestibular
      mucosa corresponding to the innervation of the buccal nerve. Eighteen months
      after the surgery, 15 of the 29 patients in the symphysis group still had some
      decreased sensitivity and presented with permanent altered sensation. Only one of
      the patients grafted from the mandibular ramus presented with permanent altered
      sensation in the posterior vestibular area. No major complication occurred in the
      donor sites in any of the 53 patients. CONCLUSION: The results of this study
      favored the use of the ascending mandibular ramus as an intraoral donor site for
      bone grafting.

PMID- 14575630
TI  - Early functional loading of unsplinted roughened surface implants with mandibular
      overdentures 2 weeks after surgery.
AB  - BACKGROUND: Before early functional loading of unsplinted implants with
      mandibular overdentures can become widespread, more clinical studies are needed
      to investigate the success of the approach. PURPOSE: To evaluate the success
      rates of two types of roughened titanium surface implants with early 2-week
      functional loading of paired mandibular interforaminal implants with
      overdentures. MATERIALS AND METHODS: Random allocation divided 24 strictly
      selected edentulous participants into two groups, with each group to receive a
      different implant system (ITI Dental Implant System, Straumann AG, Waldenburg,
      Switzerland; or Southern Implant System, Southern Implants, Irene, South Africa).
      Two implants were placed in the anterior mandible of all participants using one
      stage standardized surgical procedures. Previously constructed conventional
      mandibular dentures (opposing maxillary complete dentures) were temporarily
      relined and worn by the participants for the first 2 weeks; participants used a
      soft diet. Two weeks after implant surgery and following some mucosal healing,
      the mandibular dentures had the tissue conditioner removed and the appropriate
      matrices included for an unsplinted prosthodontic design. RESULTS: No implant
      from either group was lost. Resonance frequency analysis (RFA) indicated higher
      primary stability at surgery for the Southern group than for the ITI group, with
      a statistically significant difference between the groups throughout the study
      period. The drop in RF values between surgery and 6 weeks was significant and was
      greater for the Southern group. RFA also indicated stabilized osseointegration
      between 6 to 12 and 12 to 52 weeks, with no participant showing any decrease in
      those values over time. Participants with type 3 bone showed a significant
      improvement in RF values between 12 and 52 weeks, eventually matching those of
      participants with type 2 bone. There were no significant differences in marginal
      bone loss, periimplant parameters, or prosthodontic maintenance between the
      groups over the study period. CONCLUSIONS: Using only strict patient selection
      criteria, 1-year follow-up data indicate that early functional loading of ITI and
      Southern implants with mandibular two-implant overdentures is possible as early
      as 2 weeks after implant surgery.

PMID- 14575632
TI  - Donor site morbidity in two different approaches to anterior iliac crest bone
      harvesting.
AB  - BACKGROUND: Bone grafting is a surgical technique for the reconstruction of the
      atrophic edentulous maxilla prior to treatment with endosseous implants. The
      anterior iliac crest is a commonly used donor site. PURPOSE: The aim of this
      study was to evaluate the donor site morbidity and complications when harvesting
      corticocancellous bone from the medial table of the anterior iliac crest and
      compare this with results when bone was harvested from the lateral and superior
      table of the anterior iliac crest. In addition, the outcome of the oral
      rehabilitation was evaluated by means of a quality-of-life questionnaire.
      MATERIAL AND METHODS: The study was composed of 70 consecutively treated patients
      with a mean age of 56 years. The patients were retrospectively evaluated with
      regard to postoperative donor site morbidity and complications at the donor site.
      RESULTS: For the donor site morbidity, 74% of the patients were free of pain
      within 3 weeks, whereas 26% of the patients had a prolonged period of pain
      lasting from a few weeks to several months. For 11% of the patients, there was
      still some pain or discomfort 2 years after the grafting surgery. For gait
      disturbance the figures were similar: 79% had no problems after 3 weeks. For the
      eight patients who still had some pain after 2 years, which was considered
      permanent, three also had gait disturbance. There was a total of three major
      complications (4%), one iliac wing fracture and two neurologic injuries.
      CONCLUSION: When harvesting a large amount of unicortical corticocancellous bone
      blocks from the the superolateral site of the iliac crest with a "peel off"
      technique, morbidity and complication rates do not differ significantly compared
      with those of the traditional anterior medial approach. Oral rehabilitation with
      maxillary reconstruction with bone grafts from the iliac crest and endosseous
      implants significantly improved oral function, facial appearance, and
      recreation/social activities and resulted in an overall improvement in quality of
      life in formerly edentulous patients.

PMID- 14575633
TI  - Periimplant bone in immediately loaded titanium implants: histologic and
      histomorphometric evaluation in human. A report of two cases.
AB  - BACKGROUND: In recent years, several investigations have demonstrated, in
      clinical and histologic studies, the practicality of the use of immediate loading
      in implant dentistry. PURPOSE: The aim of the present study was to analyze the
      periimplant responses to immediately loaded implants retrieved from two patients
      after a 6-month loading period. MATERIALS AND METHODS: Three immediately loaded
      implants (two hydroxyapatite [HA] coated, one with a sandblasted surface) were
      retrieved from two patients after a 6-month loading period. The implants were
      treated to obtain thin ground sections. RESULTS: Bone was present at the
      interface with all three implants. Bone-implant contact percentage was 80.6% +/-
      4.7. Bone was present also in the thread concavities found at a distance from
      preexisting bone and in those concavities that were at the interface with the
      supracrestal tissues or with wide marrow spaces. No gaps or fibrous tissues were
      present at the interface. No inflammatory infiltrate was present at the
      interface. The mean of the sulcus depth in all three implants was 0.9 +/- 0.1 mm,
      the length of the junctional epithelium was 0.9 +/-0.05 mm, and the length of
      connective tissue contact was 1.1 +/-0.05 mm. CONCLUSIONS; Our results show that
      immediate loading of dental implants did not impede the formation of mineralized
      tissue at the interface, and it can probably be a viable alternative in implant
      dentistry.

PMID- 14575634
TI  - Three-dimensional topographic and metrologic evaluation of dental implants by
      confocal laser scanning microscopy.
AB  - BACKGROUND: Surface topography of dental implants has changed during the past few
      years; however, the last systematic study on this topic is dated 1993. PURPOSE:
      The aim of this study was to correlate dental implants by surface analysis.
      MATERIALS AND METHODS: A microtopographic analysis of 35 dental implants was
      performed using confocal laser scanning microscopy. Roughness value (Sa) and
      developed surface area (ratio, Sdr) were calculated. Implants were grouped
      according to their surface treatment: "minimally rough" with no further surface
      treatment (n = 2); ablative structured using etching or blasting (n = 17);
      titanium plasma spray coated (TPS; n = 9); coated with hydroxyapatite (HA; n =
      7). RESULTS: Most implants (n =16) showed Sa values between 3.0 and 5.0 microm.
      The developed surface area has a mean value of 13.5 and an SD of 6.52. Minimally
      rough implant surfaces show the lowest Sa values (mean 0.5 microm). Implants with
      ablative surface treatment have mean Sa values of 3.1 microm. Both groups with
      additive surface treatment (TPS and HA) present similar roughness values with a
      mean of 6.0 microm and 5.8 microm, respectively. Ratio Sdr ranges from 3.1 for
      the minimally rough implants to 11.4 for the ablative treated implants and 14.3
      for TPS-coated and 18.4 for HA-coated implants. There is a significant difference
      between the roughness and ratio values of the different groups. The topographic
      images show a typical surface according to the underlying surface treatment.
      CONCLUSIONS: We can confirm the "classic" grouping of dental implants by type of
      surface treatment into the groups minimally rough, ablative, TPS coated, and HA
      coated as these treatments lead to different ascending Sas; however, the
      additional value of the ratio Sdr including both spatial and amplitude aspects of
      the surface could not be confirmed in this study. Functional parameters
      describing the topographic differences are still lacking.

PMID- 14575635
TI  - Influence of demineralized bone matrix's embryonic origin on bone formation: an
      experimental study in rats.
AB  - BACKGROUND: There are results suggesting that differences regarding bone-inducing
      potential, in terms of amount and/or rate of bone formation, exist between
      demineralized bone matrices (DBMs) of different embryonic origins. PURPOSE: The
      aim of the present study was to examine whether the embryonic origin of DBM
      affects bone formation when used as an adjunct to guided tissue regeneration
      (GTR). MATERIALS AND METHODS: Endomembranous (EM) and endochondral (ECH) DBMs
      were produced from calvarial and long bones of rats, respectively. Prior to the
      study the osteoinductive properties of the DBMs were confirmed in six rats
      following intramuscular implantation. Following surgical exposure of the
      mandibular ramus, a rigid hemispheric Teflon capsule loosely packed with a
      standardized quantity of DBM was placed with its open part facing the lateral
      surface of the ramus in both sides of the jaw in 30 rats. In one side of the jaw,
      chosen at random, the capsule was filled with EM-DBM, whereas in the other side
      ECH-DBM was used. Groups of 10 animals were sacrificed after healing periods of
      1, 2, and 4 months, and undecalcified sections of the capsules were produced and
      subjected to histologic analysis and computer-assisted planimetric measurements.
      RESULTS: During the experiment increasing amounts of newly formed bone were
      observed inside the capsules in both sides of the animals' jaws. Limited bone
      formation was observed in the 1- and 2-month specimens, but after 4 months of
      healing, the newly formed bone in the ECH-DBM grafted sides occupied 59.1% (range
      45.6-74.7%) of the area created by the capsule versus 46.9% (range 23.0-64.0%) in
      the EM-DBM grafted sides (p =.01). CONCLUSION: It is concluded that the embryonic
      origin of DBM influences bone formation by GTR and that ECH-DBM is superior to EM
      DBM.

PMID- 14575636
TI  - Enhancement of osseointegration of implants placed into extraction sockets of
      healthy and periodontally diseased teeth by using graft material, an ePTFE
      membrane, or a combination.
AB  - BACKGROUND: Advanced periodontal disease as well as failed endodontic teeth are
      the most common reasons for tooth removal and simultaneous implant placement.
      PURPOSE: To determine whether the addition of a bone substitute graft material
      and/or a guided bone regeneration membrane added to the site of an immediately
      placed implant would increase the development of lamellated bone, particularly in
      the presence of bone defects. MATERIALS AND METHODS: Four treatment modalities
      associated with the immediate placement of hydroxyapatite-coated endosteal screw
      implants into extraction sockets of healthy (C/H) and periodontally diseased
      teeth (T/PD) were tested. Five dogs with healthy teeth and five dogs with
      naturally occurring periodontitis were chosen for the study. Each dog received
      eight implants after extraction of four mandibular and four maxillary premolars.
      Four implants were submerged for 3 months and four for 6 months. The implants
      were either inserted alone (subgroup A); surrounded by a GORE-TEX membrane
      (subgroup B; W.L. Gore & Associates Inc., Flagstaff, AZ, USA); surrounded by
      PepGen P-15 (Dentsply Friadent CeraMed Dental Co. Denver, CO, USA) at coronal
      area (subgroup C); or surrounded by a combination of graft material and the ePTFE
      membrane (subgroup D). Implants in group A were osseointegrated in both C/H and
      T/PD groups with similar bone-implant contact ratios (BICRs). RESULTS: ePTFE
      membrane significantly improved the BICR of the 6-months implants, whereas graft
      material significantly increased the BICR at 3 months and maintained the gain
      thereafter. The graft material and membrane combination further improved the BICR
      and significantly increased lamellated bone in crestal bone of all implants.
      CONCLUSIONS: This study provides experimental evidence in support of use of graft
      material with immediately placed implants, particularly in presence of bone
      defects that initially reduce the BICR such as in periodontitis. Adding an ePTFE
      membrane to graft material resulted in a greater replacement of woven bone by
      lamellated bone. Clinical trials in humans are recommended as a follow-up of this
      experimental study.

PMID- 14575637
TI  - Inhibition and reversal of nickel-induced transformation by the histone
      deacetylase inhibitor trichostatin A.
AB  - The carcinogenic process initiated by nongenotoxic carcinogens involves
      modulation of gene expression. Nickel compounds have low mutagenic activity, but
      are highly carcinogenic. In vitro both mouse and human cells can be efficiently
      transformed by soluble and insoluble nickel compounds to anchorage-independent
      growth. Because previous studies have shown that carcinogenic nickel compounds
      silence genes by inhibiting histone acetylation and enhancing DNA methylation, we
      investigated the effect of enhancing histone acetylation on cell transformation.
      The exposure of nickel-transformed cells to the histone deacetylase inhibitor
      trichostatin A (TSA) resulted in the appearance of significant number of
      revertants measured by their inability to grow in soft agar. Using the Affymetrix
      GeneChip we found that the level of expression of a significant number of genes
      was changed (suppressed or upregulated) in nickel-transformed clones but returned
      to a normal level in revertants obtained following TSA treatment. Moreover, we
      found that treatment of cells with TSA inhibited the ability of nickel to
      transform mouse PW cells to anchorage-independent growth. Treatment with TSA also
      inhibited the ability of nickel to transform human HOS cells, although to a
      lesser extent. In contrast, treatment with TSA was not able to revert established
      cancer cell lines as readily as the nickel-transformed cells. These data
      indicated that modulation of gene expression is important for nickel-induced
      transformation.

PMID- 14575638
TI  - Mitogen activated protein kinases selectively regulate palytoxin-stimulated gene
      expression in mouse keratinocytes.
AB  - We have been investigating how the novel skin tumor promoter palytoxin transmits
      signals through mitogen activated protein kinases (MAPKs). Palytoxin activates
      three major MAPKs, extracellular signal-regulated kinase (ERK), c-Jun N-terminal
      kinase (JNK), and p38, in a keratinocyte cell line derived from initiated mouse
      skin (308). We previously showed that palytoxin requires ERK to increase matrix
      metalloproteinase-13 (MMP-13) gene expression, an enzyme implicated in
      carcinogenesis. Diverse stimuli require JNK and p38 to increase MMP-13 gene
      expression, however. We therefore used the JNK and p38 inhibitors SP 600125 and
      SB 202190, respectively, to investigate the role of these MAPKs in palytoxin
      induced MMP-13 gene expression. Surprisingly, palytoxin does not require JNK and
      p38 to increase MMP-13 gene expression. Accordingly, ERK activation, independent
      of palytoxin and in the absence of JNK and p38 activation, is sufficient to
      induce MMP-13 gene expression in 308 keratinocytes. Dexamethasone, a synthetic
      glucocorticoid that inhibits activator protein-1 (AP-1), blocked palytoxin
      stimulated MMP-13 gene expression. Therefore, the AP-1 site present in the
      promoter of the MMP-13 gene appears to be functional and to play a key role in
      palytoxin-stimulated gene expression. Previous studies showed that palytoxin
      simulates an ERK-dependent selective increase in the c-Fos content of AP-1
      complexes that bind to the promoter of the MMP-13 gene. JNK and p38 can also
      modulate c-Fos. Palytoxin does not require JNK or p38 to increase c-Fos binding,
      however. Altogether, these studies indicate that ERK plays a distinctly essential
      role in transmitting palytoxin-stimulated signals to specific nuclear targets in
      keratinocytes derived from initiated mouse skin.

PMID- 14575640
TI  - Neocarzinostatin-induced Rad51 nuclear focus formation is cell cycle regulated
      and aberrant in AT cells.
AB  - DNA double-stranded breaks are the most detrimental form of DNA damage and, if
      not repaired properly, may lead to an accumulation of chromosomal aberrations and
      eventually tumorigenesis. Proteins of the Rad51/Rad52 epitasis group are crucial
      for the recombinational repair of DNA double-stranded breaks, whereas the
      Rad50/NBS1/Mre11 nuclease complex is involved in both the recombinational and the
      end-joining repair of DNA double-stranded breaks. Herein, we demonstrate that the
      chemotherapeutic enediyne antibiotic neocarzinostatin induced Rad51, but not
      NBS1, nuclear focus formation in a cell- cycle-dependent manner. Furthermore,
      neocarzinostatin-induced Rad51 foci formation revealed a slower kinetic change in
      AT cells, but not in wild-type or NBS cells. In summary, our results suggest that
      neocarzinostatin induces Rad51 focus formation through an ATM- and cell-cycle
      dependent, but NBS1-independent, pathway.

PMID- 14575639
TI  - Ochratoxin A affects COS cell adhesion and signaling.
AB  - Ochratoxin A (OTA), a metabolite produced by strains of Aspergillus and
      Penicillium, has nephritogenic, carcinogenic, and teratogenic activity in animals
      and humans. Nanomolar concentrations of OTA promote apoptosis in a cell-type
      specific fashion. In this study, we have analyzed the molecular mechanism by
      which OTA affects COS cell adhesion and signaling resulting in an apoptotic
      response. OTA, at noncytotoxic doses, was able to detach collagen- and
      fibronectin-adherent cells from immobilized substratum. However, prior to
      inducing detachment of adherent cells, OTA caused apoptosis as measured by
      caspase-3 activation. The treatment of adherent cells by OTA caused a reduction
      of tyrosine phosphorylation levels of FAK and of the adapter protein paxillin.
      The down-regulation of FAK preceded apoptosis and cell detachment induced by OTA.
      The mycotoxin was also able to cause a decrease of the phosphorylation levels of
      the two Shc isoforms, P66 and P52, in adherent cells. Since these Shc isoforms
      have been implicated in the activation of protein kinase c-Src, which is required
      for FAK tyrosine phosphorylation, the observed dephosphorylation of FAK and of
      the FAK substrate paxillin by OTA could be ascribed to the early down-regulation
      of Shc isoforms. However, whether FAK and Shc phosphorylation contribute both to
      the same pathway leading to the induction of apoptosis by OTA or are involved in
      two parallel signaling pathways remains to be investigated.

PMID- 14575641
TI  - Rapid in vitro chemosensitivity analysis of human colon tumor cell lines.
AB  - In oncology, diagnostic assays have the potential to individualize treatment. Due
      to a large number of chemotherapeutic agents available, a chemosensitivity assay
      would be of great value for patients receiving chemotherapy. However, no broadly
      accepted test exists to date. Our work aims at establishing a chemosensitivity
      test using a microphysiometer, a device that measures the extracellular
      acidification rate of cells. The test assesses chemosensitivity by comparing the
      acidification rate of cells treated with cytostatic agents with that of
      nontreated cells. We performed experiments with two human colon tumor cell lines,
      HCT 116 and SW620, and cytostatic agents commonly used in therapy of colon
      carcinoma. We showed that a chemosensitivity test can be reproducibly performed
      using a microphysiometer. Suitable media and conditions for the assay were found.
      Test results were further correlated with the crystal violet assay and a
      tetrazolium salt assay. In comparison, cytostatic effects were rapidly and most
      clearly displayed with the microphysiometer. Our results suggest that
      microphysiometry is a promising platform for chemosensitivity testing.

PMID- 14575642
TI  - Cytostatic activity of antiviral acyclic nucleoside phosphonates in rodent
      lymphocytes.
AB  - Acyclic nucleoside phosphonates (ANPs) inhibit replication of both DNA viruses
      and retroviruses, including HIV. The major mechanism of their antiviral action is
      inhibition of virus-induced DNA polymerases and/or of reverse transcriptases. We
      investigated the effects of ANPs on proliferation of mitogen-stimulated mouse and
      rat splenocytes. Included in the study were compounds differing at the
      heterocyclic base, i.e., adenine (A) and 2,6-diaminopurine (DAP), and at the N(9)
      side chain, i.e., 9-[2-(phosphonomethoxy)ethyl] (PME) and (R)- or (S)-enantiomers
      of 9-[2-(phosphonomethoxy)propyl] (PMP) moieties, and their numerous N(6)
      substituted derivatives. The medial inhibitory concentrations (IC50) of N(6)
      nonsubstituted compounds range from 0.13 (PMEDAP) to 354 microM ((R)-PMPA).
      Antiproliferative effects are more pronounced in PME than in PMP series, and they
      are more prominent in DAP compared to A analogs. The (S)-enantiomers of PMP
      series are more effective than corresponding (R)-congers. The highest cytostatic
      potential is exhibited by N(6)-allyl-PMEDAP (IC50 = 0.017 microM) and N(6)
      cyclopropyl-PMEDAP (IC50 = 0.036 microM). The N(6)-substituted derivatives of (S)
      PMPA are virtually devoid of cytostatic activity. No tight correlation between
      the cytostatic and reported antiviral effects could be detected.

PMID- 14575643
TI  - Octamethylcyclotetrasiloxane exhibits estrogenic activity in mice via ERalpha.
AB  - Octamethylcyclotetrasiloxane (D4) is a low molecular weight cyclic silicone used
      in the synthesis of larger silicone polymers and in the formulation of a variety
      of personal care products. The effects of oral D4 exposure in mice on serum
      estradiol levels, uterine wet weight, and uterine peroxidase activity were
      investigated. Additionally, in vitro estrogen receptor binding activity was
      evaluated. Serum estradiol levels decreased in a dose-dependent manner after
      exposure to 100 mg/kg to 1000 mg/kg D4. Studies with adrenalectomized animals
      demonstrated that the decreased serum estradiol levels were not due to elevated
      serum corticosterone levels. Uterine wet weights in ovariectomized mice were
      significantly increased in a dose-dependent manner by exposure to 250-1000 mg of
      D4/kg, but not by exposure to other silicone compounds tested
      (hexamethylcyclotrisiloxane, decamethylcyclopentasiloxane,
      decamethyltetrasiloxane, and octaphenylcyclotetrasiloxane). Uterine peroxidase
      activity, a marker for estrogenic activity, was also significantly increased in
      D4-exposed mice, but not in mice exposed to the other siloxanes. Pretreating mice
      with the estrogen receptor antagonist ICI 182,780 completely blocked the D4
      induced increase in uterine weight, and ovariectomized estrogen receptor-alpha
      knockout mice showed no increases in uterine weights when orally exposed to D4 or
      estradiol. In an in vitro estrogen receptor binding assay, D4 showed significant
      competition with (3)H-estradiol for binding to estrogen receptor-alpha, but not
      estrogen receptor-beta. The data presented here indicate that D4 has weak
      estrogenic activity, and that these effects are mediated through estrogen
      receptor-alpha.

PMID- 14575644
TI  - TCDD-induced expression of Ah receptor responsive genes in the pituitary and
      brain of cellular retinol-binding protein (CRBP-I) knockout mice.
AB  - The 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) is a highly toxic,
      widespread environmental contaminant. Most of the toxic damage caused by TCDD is
      considered to be secondary to the binding of TCDD to the aryl hydrocarbon
      receptor, the AH receptor (AHR). TCDD is known to affect the vitamin A
      homeostasis. The effects of TCDD on body weight and on the expressions of AHR
      associated genes may be modulated by the retinoid system. Therefore, we
      investigated the regulation pattern of expression of the AHR associated genes
      after TCDD exposure in wild-type 129/SV/C57BL/6 mice and in mice deficient in
      cellular retinol-binding protein type I (CRBP-I) of the same mixed genetic
      background. A single oral dose of TCDD (50 or 250 mug/kg) was administrated by
      gavage. Different brain areas, including cortex, hypothalamus, cerebellum, and
      olfactory bulb, as well as pituitary and liver, were dissected from CRBP-I
      knockout homozygous mice (-/-) and wild-type mice (+/+) killed at two time points
      (7 or 28 days after treatment). Compared with vehicle-treated controls, the
      relative levels of cytochrome P450 1A1 (CYP1A1) mRNA and protein expression in
      TCDD-treated animals were dramatically increased in mice of both CRBP-I genotypes
      (-/-, +/+). CYP1A1 mRNA levels increased up to 1400-fold in the pituitary, 110
      fold in the brain, and up to 1600-fold in the liver. A general observation was
      that the relative induction of CYP1A1 and AHR transcription after TCDD dosing was
      highest in the +/+ mice. A high TCDD-induced aryl hydrocarbon receptor repressor
      (AHRR) mRNA expression was observed in the liver and in brain tissues.
      Interestingly, however, mice that lacked the CRBP-I protein (-/-) were found to
      have a significantly higher basal expression of AHRR gene in the pituitary
      compared to the wild-type (CRBP-I +/+) mice and in accordance a less pronounced
      induction of CYP1A1 and AHR was observed in the pituitary of the -/- mice.
      Immunohistochemical double staining analyses of the expression pattern of CYP1A1
      and AHRR proteins in the pituitary revealed a colocalization of these two
      proteins. We conclude that the vitamin A homeostasis seems to have some influence
      to the TCDD-induced activation of AHR-regulated gene transcription in the brain
      and pituitary of the adult mouse.

PMID- 14575645
TI  - T cell receptor transgenic mice provide novel insights into understanding
      cellular targets of TCDD: suppression of antibody production, but not the
      response of CD8(+) T cells, during infection with influenza virus.
AB  - Although exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) clearly impairs T
      cell-dependent immune responses, the mechanisms underlying TCDD-induced T cell
      dysfunction are unclear. With the goal of determining precisely how exposure to
      TCDD impairs the activation of CD8(+) T cells in vivo, we used a well-defined T
      cell receptor (TCR) transgenic system. Greater than 95% of the CD8(+) T cells in
      F5 transgenic mice possess TCR specific for a peptide from influenza A virus
      expressed in the context of H-2D(b). Unexpectedly, we discovered that exposure to
      TCDD did not alter CD8(+) T cell function in the transgenic mice. Specifically,
      treatment of F5 mice with TCDD did not affect the recruitment of virus-specific
      CD8(+) T cells to the lung, nor did it impair the ability of CD8(+) T cells in
      the lymph node to produce cytokines, or to clonally expand or differentiate. This
      is in direct contrast to the suppressive effects of TCDD on the response of
      CD8(+) T cells in wild-type mice. Exposure of F5 mice to TCDD induced CYP1A1 and
      suppressed the production of virus-specific antibodies. Likewise, upon adoptive
      transfer into wild-type mice, TCDD suppressed the expansion and differentiation
      of F5-derived CD8(+) T cells. This indicates that the F5 mice and lymphocytes
      derived from them are not inherently resistant to the immunosuppressive effects
      of TCDD. Rather, our data suggest that in the context of a supraphysiological
      number of antigen-specific CD8(+) T cells, the function of these cells was not
      affected by exposure to TCDD. Given that antibody production in the F5 mice was
      sensitive to suppression by TCDD, while the CD8 response was resistant, our data
      provide a new perspective on the ways in which exposure to TCDD adversely affects
      B and T lymphocyte function.

PMID- 14575646
TI  - Differential up-regulation of striatal dopamine transporter and alpha-synuclein
      by the pyrethroid insecticide permethrin.
AB  - The effects of permethrin on striatal dopaminergic biomarkers were assessed in
      this study. Retired breeder male C57 B1/6 mice were given an ip dose of
      permethrin (0.1-200 mg/kg) at 7-day intervals, over a 2-week period (Days 0, 7,
      and 14). Animals were then sacrificed 1 day (t = 1), 14 days (t = 14), or 28 days
      after the last treatment (t = 28). Dopamine transporter (DAT) protein as assayed
      by Western blotting was increased to 115% in the 0.8 mg/kg group over that of
      control mice at t = 1 (P < 0.05). At t = 14, this value increased to 140% of
      control, and declined slightly to 133% of control at t = 28. The mice given the
      1.5 mg/kg dose displayed a significant increase in DAT protein only at t = 28, to
      145% of controls. Thus, upregulation of the DAT at low doses of PM is variable 24
      h after treatment, and seems to stabilize by t = 28. The threshold dose for
      increasing DAT expression in Western blots by t = 28 was 0.2 mg/kg permethrin.
      [(3)H]GBR 12935, used to assay DAT binding, followed the same trend as that for
      the Western blotting data for 0.8 and 1.5 mg/kg doses of permethrin over the 4
      weeks posttreatment. At 200 mg/kg permethrin, DAT protein was unchanged vs
      controls (t = 1), but had significantly increased by t = 14 and continued to
      increase at t = 28, suggesting that the reduced dopamine transport at this dose
      was due to nerve terminal stress and that recovery had occurred. The protein
      alpha-synuclein was also significantly induced at the 1.5 mg/kg dose at t = 1;
      however, unlike DAT up-regulation, this effect had declined to control values by
      t = 14. Maximal induction of alpha-synuclein protein occurred at a dose of 50
      mg/kg permethrin. These data provide evidence that the pyrethroid class of
      insecticides can modulate the dopaminergic system at low doses, in a persistent
      manner, which may render neurons more vulnerable to toxicant injury.

PMID- 14575647
TI  - Cyclooxygenases in the skin: pharmacological and toxicological implications.
AB  - Cyclooxygenase (COX), a prostaglandin-endoperoxide synthase (PTGS), catalyzes the
      formation of prostaglandins from arachidonic acid. Prostaglandins are lipid
      signaling mediators that play a central role in a broad range of diverse
      physiological and pathophysiological processes, including inflammation,
      reproduction, nocioception, and gastrointestinal protection. Inhibition of
      cyclooxygenase activity is the mechanism by which nonsteroidal antiinflammatory
      drugs (NSAIDS) exert their analgesic, antipyretic, antiinflammatory, and
      antithrombotic effects. COX is currently believed to exist in three isoforms. In
      this review, we provide a concise state-of-the-art description of the role of COX
      in pharmacology and toxicology of skin including its involvement in normal
      physiology, cutaneous inflammation, nociception, wound healing, and
      tumorigenesis. COX-dependent pathways influence keratinocyte differentiation,
      hair follicle development, and hair growth. The critical role of COX-2 in
      pathophysiology of skin is also addressed. COX-2 mediates inflammatory processes
      in skin, including inflammatory hyperalgesia and nociception, and administration
      of specific COX-2 inhibitors reduces edema, vascular permeability, and other
      markers of cutaneous inflammation. A number of studies in animal models and in
      humans show that COX-2 inhibitors possess cancer chemopreventive properties.
      Selective COX-2 inhibitors have a more favorable side-effect profile. Topical
      formulations of COX-2 inhibitors are being developed as a novel pharmacologic
      approach for the treatment of COX-2 mediated skin diseases.

PMID- 14575648
TI  - Diclofenac-induced liver injury: a paradigm of idiosyncratic drug toxicity.
AB  - The nonsteroidal antiinflammatory drug diclofenac causes rare but significant
      cases of serious hepatotoxicity, typically with a delayed onset (>1-3 months).
      Because there is no simple dose relationship and because liver injury cannot be
      reproduced in current animal models, individual patient-specific susceptibility
      factors have been evoked to account for the increased risk. While these patient
      factors have remained undefined, a number of molecular hazards have been
      characterized. Among these are metabolic factors (bioactivation by hCYP2C9 or
      hCYP3A4 to thiol-reactive quinone imines, activation by hUGT2B7 to protein
      reactive acyl glucuronides and iso-glucuronides, and 4'-hydroxylation secondary
      to diclofenac glucuronidation), as well as kinetic factors (Mrp2-mediated
      concentrative transport of diclofenac metabolites into bile). From the
      toxicodynamic view, both oxidative stress (caused by putative diclofenac cation
      radicals or nitroxide and quinone imine-related redox cycling) and mitochondrial
      injury (protonophoretic activity and opening of the permeability transition pore)
      alone or in combination have been implicated in diclofenac toxicity. In some
      cases, immune-mediated liver injury is involved, inferred from inadvertent
      rechallenge data and from a number of experiments demonstrating T cell
      sensitization. Why certain underlying diseases (e.g., osteoarthritis) also
      increase the susceptibility to diclofenac hepatotoxicity is not clear. To date,
      cumulative damage to mitochondrial targets seems a plausible putative mechanism
      to explain the delayed onset of liver failure, perhaps even superimposed on an
      underlying silent mitochondrial abnormality. Increased efforts to identify both
      patient-specific risk factors and disease-related factors will help to define
      patient subsets at risk as well as increase the predictability of unexpected
      hepatotoxicity in drug development.

PMID- 14575649
TI  - Does tumor growth follow a "universal law"?
AB  - A general model for the ontogenetic growth of living organisms has been recently
      proposed. Here we investigate the extension of this model to the growth of solid
      malignant tumors. A variety of in vitro and in vivo data are analysed and
      compared with the prediction of a "universal" law, relating properly rescaled
      tumor masses and tumor growth times. The results support the notion that tumor
      growth follows such a universal law. Several important implications of this
      finding are discussed, including its relevance for tumor metastasis and
      recurrence, cell turnover rates, angiogenesis and invasion.

PMID- 14575650
TI  - An in silico investigation into the causes of telomere length heterogeneity and
      its implications for the Hayflick limit.
AB  - In telomerase-negative cell populations the mean telomere length (TL) decreases
      with increasing population doubling number (PD). A critically small TL is
      believed to stop cell proliferation at a cell-, age- and species-specific PD thus
      defining the Hayflick limit. However, positively skewed TL distributions are
      broad compared to differences between initial and final mean TL and strongly
      overlap at middle and late PD, which is inconsistent with a limiting role of TL.
      We used computer-assisted modelling to define what set of premises may account
      for the above. Our model incorporates the following concepts. DNA end replication
      problem: telomeres loose 1 shortening unit (SU) upon each cell division. Free
      radical-caused TL decrease: telomeres experience random events resulting in the
      loss of a random SU number within a remaining TL. Stochasticity of gene
      expression and cell differentiation: cells experience random events inducing
      mitoses or committing cells to proliferation arrest, the latter option requiring
      a specified number of mitoses to be passed. Cells whose TL reaches 1SU cannot
      divide. The proliferation kinetics of such virtual cells conforms to the
      transition probability model of cell cycle. When no committing events occur and
      at realistic SU estimates of the initial TL, maximal PD values far exceed the
      Hayflick limit observed in normal cells and are consistent with the crisis stage
      entered by transformed cells that have surpassed the Hayflick limit. At
      intermediate PD, symmetrical TL distributions are yielded. Upon introduction of
      committing events making the ratio of the rates of proliferating and committing
      events (P/C) range from 1.10 to 1.25, TL distributions at intermediate PD become
      positively skewed, and virtual cell clones show bimodal size distributions. At
      P/C as high as 1.25 the majority of virtual cells at maximal PD contain telomeres
      with TL>1SU. A 10% increase in P/C within the 1.10-1.25 range produces a two-fold
      increase in the maximal PD, which can reach values of up to 25 observed in rodent
      and some human cells. Increasing the number of committed mitoses from 0 to 10 can
      increases PD to about 50 observed in human fibroblasts. Introduction of the
      random TL breakage makes the shapes of TL distributions quite dissimilar from
      those observed in real cells. CONCLUSIONS: Telomere length decrease is a
      correlate of cell proliferation that cannot alone account for the Hayflick limit,
      which primarily depends on parameters of cell population kinetics. Free radical
      damage influences the Hayflick limit not through TL but rather by affecting the
      ratio of the rates of events that commit cells to mitoses or to proliferation
      arrest.

PMID- 14575651
TI  - Simultaneous analysis of prompt and delayed chlorophyll a fluorescence in leaves
      during the induction period of dark to light adaptation.
AB  - An attempt is made to reveal the relation between the induction curves of delayed
      fluorescence (DF) registered at 0.35-5.5 ms and the prompt chlorophyll
      fluorescence (PF). A simple formulation was proposed to link the ratio of the
      transient values of delayed and variable fluorescence with the redox state of the
      primary electron acceptor of Photosystem II--QA, and the thylakoid membrane
      energization. The term luminescence potential (UL) was introduced, defined as the
      sum of the redox potential of QA and the transmembrane proton gradient. It was
      shown that UL is proportional to the ratio of DF to the variable part of PF. The
      theoretical model was verified and demonstrated by analysing induction courses of
      PF and millisecond DF, simultaneously registered from leaves of barley--wild-type
      and the chlorophyll b-less mutant chlorina f2. A definitive correlation between
      PF and DF was established. If the luminescence changes are strictly due to UL,
      the courses of DF and PF are reciprocal and the millisecond DF curve resembles
      the first derivative of the PFt function.

PMID- 14575652
TI  - Network-based analysis of metabolic regulation in the human red blood cell.
AB  - Reconstruction of cell-scale metabolic networks is now possible. A description of
      allowable metabolic network functions can be obtained using extreme pathways,
      which are the convex basis vectors of the solution space containing all steady
      state flux distributions. However, only a portion of these allowable network
      functions are physiologically possible due to kinetic and regulatory constraints.
      Methods are now needed that enable us to take a defined metabolic network and
      deduce candidate regulatory structures that control the selection of these
      physiologically relevant states. One such approach is the singular value
      decomposition (SVD) of extreme pathway matrices (P), which allows for the
      characterization of steady state solution spaces. Eigenpathways, which are the
      left singular vectors from the SVD of P, can be described and categorized by
      their biochemical function. SVD of P for the human red blood cell showed that the
      first five eigenpathways, out of a total of 23, effectively characterize all the
      relevant physiological states of red blood cell metabolism calculated with a
      detailed kinetic model. Thus, with five degrees of freedom the magnitude and
      nature of the regulatory needs are defined. Additionally, the dominant features
      of these first five eigenpathways described key metabolic splits that are indeed
      regulated in the human red blood cell. The extreme pathway matrix is derived
      directly from network topology and only knowledge of Vmax values is needed to
      reach these conclusions. Thus, we have implemented a network-based analysis of
      regulation that complements the study of individual regulatory events. This
      topological approach may provide candidate regulatory structures for metabolic
      networks with known stoichiometry but poorly characterized regulation.

PMID- 14575653
TI  - A logistic branching process for population genetics.
AB  - A logistic (regulated population size) branching process population genetic model
      is presented. It is a modification of both the Wright-Fisher and (unconstrained)
      branching process models, and shares several properties including the coalescent
      time and shape, and structure of the coalescent process with those models. An
      important feature of the model is that population size fluctuation and regulation
      are intrinsic to the model rather than externally imposed. A consequence of this
      model is that the fluctuation in population size enhances the prospects for
      fixation of a beneficial mutation with constant relative viability, which is
      contrary to a result for the Wright-Fisher model with fluctuating population
      size. Explanation of this result follows from distinguishing between expected and
      realized viabilities, in addition to the contrast between absolute and relative
      viabilities.

PMID- 14575654
TI  - Scale-dependence of resource-biodiversity relationships.
AB  - The functional relationship between resource availability and species richness is
      addressed at different spatial scales. We analyse the smaller, community, scale
      by using a multi-species contact process coupled to a heterogeneous landscape,
      i.e. a stochastic spatial model of individual behavior in a system with limited
      resources. Using percolation theory, the theory of competitive exclusion
      processes, and the results of Monte Carlo simulations we show that a unimodal
      resource-species relationship may be understood as a tradeoff between the
      availability and connectivity of resource patches. We then pose the question of
      how resource-species relationships may be scaled up to the larger, regional,
      level and discuss the theoretical basis for differences in behavior at different
      scales. Regional ecosystems are modeled as statistical aggregates of dynamically
      driven small-scale ecosystems. Observing a transition from a unimodal
      relationship at small scales to a monotonically increasing relationship at large
      scales is shown to be contingent on the presence of a resource-dependent species
      pool. Finally, we confirm our theoretical prediction of a transition via Monte
      Carlo simulations of regional landscapes and discuss the potential complicating
      effects of spatial correlations in the distribution of both resources and
      species.

PMID- 14575655
TI  - Thermodynamical interpretation of an adaptive walk on a Mt. Fuji-type fitness
      landscape: Einstein relation-like formula holds in a stochastic evolution.
AB  - We have theoretically studied the statistical properties of adaptive walks (or
      hill-climbing) on a Mt. Fuji-type fitness landscape in the multi-dimensional
      sequence space through mathematical analysis and computer simulation. The
      adaptive walk is characterized by the "mutation distance" d as the step-width of
      the walker and the "population size" N as the number of randomly generated d-fold
      point mutants to be screened. In addition to the fitness W, we introduced the
      following quantities analogous to thermodynamical concepts: "free fitness" G(W)
      is identical with W+T x S(W), where T is the "evolutionary temperature" T
      infinity square root of d/lnN and S(W) is the entropy as a function of W, and the
      "evolutionary force" X is identical with d(G(W)/T)/dW, that is caused by the
      mutation and selection pressure. It is known that a single adaptive walker
      rapidly climbs on the fitness landscape up to the stationary state where a
      "mutation-selection-random drift balance" is kept. In our interpretation, the
      walker tends to the maximal free fitness state, driven by the evolutionary force
      X. Our major findings are as follows: First, near the stationary point W*, the
      "climbing rate" J as the expected fitness change per generation is described by J
      approximately L x X with L approximately V/2, where V is the variance of fitness
      distribution on a local landscape. This simple relationship is analogous to the
      well-known Einstein relation in Brownian motion. Second, the "biological
      information gain" (DeltaG/T) through adaptive walk can be described by combining
      the Shannon's information gain (DeltaS) and the "fitness information gain"
      (DeltaW/T).

PMID- 14575656
TI  - A careful physical analysis of gas bubble dynamics in xylem.
AB  - Many studies have confirmed that cavitation in xylem is caused by air bubbles.
      Recently Shen et al. (Tree Physiol. 22 (2002) R655), analysed the expansion of a
      pre-existent bubble in xylem and one formed by air seeding. The present paper
      makes a further analysis of bubble expansion by the equilibrium criterion of the
      Helmholtz function. It has been proved that when xylem pressure P'l decreases to
      a special value P'l* from a value higher than, or equal to, or lower than -Po (Po
      is atmospheric pressure), an air bubble in xylem can grow up steadily,
      corresponding to minimums of the Helmholtz function F(r). As soon as P'l is lower
      than P'l*, since F(r) will be a decreasing function when P'l < P'l*, resulting in
      non-equilibrium of the bubble, it will break inducing a cavitation event. The
      analysis is consistent with the results of mechanism. Given P'l > or = -3Po, if
      an air bubble could enter a conduit, it would be in a stable equilibrium. When
      P'l < -3Po an air bubble entering a conduit will be in an unstable equilibrium.
      As the water further vaporizes, it will break at once. This is the case to which
      the former published formula P'l = -2sigma/rp is applicable.

PMID- 14575657
TI  - Bicoordinate navigation based on non-orthogonal gradient fields.
AB  - The mathematically exact solution for navigating with respect to two non
      orthogonal gradient fields requires taking both fields into account conjointly.
      Such a complex solution may be beyond the brain capability of most animals.
      Animals may use an approximate, simpler solution by considering each field
      separately (i.e., the angle between the two gradient directions is ignored). This
      generates directional biases that may prove useful in determining the nature of
      the fields actually involved in bicoordinate navigation.

PMID- 14575658
TI  - Spatially explicit modelling of transgenic maize pollen dispersal and cross
      pollination.
AB  - Modelling of pollen dispersal and cross-pollination is of great importance for
      the ongoing discussion on thresholds for the adventitious presence of genetically
      modified material in food and feed. Two different modelling approaches for pollen
      dispersal are used to simulate the cross-pollination rate of pollen emerged from
      an adjacent transgenic crop field. The models are applied to cross-pollination
      data from field experiments with transgenic maize (Zea mays). The data were
      generated by an experimental setup specifically designed to suit the demands of
      mathematical modelling. First a Gaussian plume model is used for the simulation
      of pollen transport in and from plant canopies. This is a semiempirical approach
      combining the atmospheric diffusion equation and Lagrangian methodology. The
      second model is derived from the localised near field (LNF) theory and based on
      the physical processes in the canopy. Both modelling approaches prove to be
      appropriate for the simulation of the cross-pollination rates at distances of
      about 7.5m and more from the transgene source. The simulation of the cross
      pollination rate is less precise at the edge of the source plot especially with
      the LNF theory. However, the simulation results lie within the range of
      variability of the observations. Concluding can be pointed out that both models
      might be adapted to other pollen dispersal experiments of different crops and
      plot sizes.

PMID- 14575659
TI  - A cellular automaton model for tumour growth in inhomogeneous environment.
AB  - Most of the existing mathematical models for tumour growth and tumour-induced
      angiogenesis neglect blood flow. This is an important factor on which both
      nutrient and metabolite supply depend. In this paper we aim to address this
      shortcoming by developing a mathematical model which shows how blood flow and red
      blood cell heterogeneity influence the growth of systems of normal and cancerous
      cells. The model is developed in two stages. First we determine the distribution
      of oxygen in a native vascular network, incorporating into our model features of
      blood flow and vascular dynamics such as structural adaptation, complex rheology
      and red blood cell circulation. Once we have calculated the oxygen distribution,
      we then study the dynamics of a colony of normal and cancerous cells, placed in
      such a heterogeneous environment. During this second stage, we assume that the
      vascular network does not evolve and is independent of the dynamics of the
      surrounding tissue. The cells are considered as elements of a cellular automaton,
      whose evolution rules are inspired by the different behaviour of normal and
      cancer cells. Our aim is to show that blood flow and red blood cell heterogeneity
      play major roles in the development of such colonies, even when the red blood
      cells are flowing through the vasculature of normal, healthy tissue.

PMID- 14575660
TI  - The rescaling method for quantifying the turnover of cell populations.
AB  - The dynamic nature of immune responses requires the development of appropriate
      experimental and theoretical tools to quantitatively estimate the division and
      death rates which determine the turnover of immune cells. A number of papers have
      used experimental data from BrdU and D-glucose labels together with a simple
      random birth-death model to quantify the turnover of immune cells focusing on
      HIV/SIV infections [Mohri et al. 279 (1998) 1223-1227, Hellerstein et al. 5
      (1999) 83-89, Bonhoeffer et al. 164 (2000) 5049-5054, Mohri et al. 87 (2001) 1277
      1287]. We show how uncertainties in the assumptions of the random birth-death
      model may lead to substantial errors in the parameters estimated. We then show
      how more accurate estimates can be obtained from the more recent CFSE data which
      allow to track the number of divisions each cell has undergone. Specifically, we:
      (i) describe a general stage-structured model of cell division where the
      probabilities of division and death are functions of time since the previous
      division; (ii) develop a rescaling method to identify invariant parameters (i.e.
      the ones that are independent of the specific functions describing division and
      death); (iii) show how these invariant parameters can be estimated, and (iv)
      illustrate this technique by applying it to CFSE data taken from the literature.

PMID- 14575661
TI  - Lamotrigine for intractable sciatica: correlation between dose, plasma
      concentration and analgesia.
AB  - An open trial was conducted to study the potential efficacy of the antiepileptic
      agent lamotrigine in relieving the sciatic pain and the relationship between
      lamotrigine dosage, plasma concentration and the clinical response. Subsequent to
      a 1 week washout period from previous analgesics, lamotrigine dose was titrated
      on a weekly basis from 25 to 400mg/day and was maintained at that dose for
      additional 4 weeks. Spontaneous pain, the Short Form McGill Pain Questionnaire
      (SFMPQ), the Straight Leg Raise (SLR) test, and range of motion of the lumbar
      spine (leaning foreword, to the affected side) were used to assess lamotrigine
      efficacy. Lamotrigine plasma concentration was tested at the end of each week
      during the titration period and at the end of the study. Fourteen patients were
      enrolled in the study. All outcome measurers improved compared to baseline during
      the titration period, but reached a statistically significant level of
      improvement only at the 400mg dose. A linear correlation was found between mean
      lamotrigine dose, mean plasma concentration and mean weekly spontaneous pain,
      mean SLR and mean bending the affected side, but not with the SFMPQ score. Study
      results suggest lamotrigine is a potentially effective and safe compound for the
      treatment of painful lumbar radiculopathy, and that it is likely to act in a dose
      and plasma concentration-dependent fashion.

PMID- 14575662
TI  - Nerve terminals extend into the temporomandibular joint of adjuvant arthritic
      rats.
AB  - The innervation of the temporomandibular joint (TMJ) has attracted particular
      interest because of the close association with complex mandibular movement.
      Although the pathological changes of disk innervation may have a crucial role in
      the development of TMJ pain, the innervation of the TMJ disk by experimentally
      induced arthritis has rarely been examined in detail. Arthritic rats were induced
      by injection with 0.1ml solution of Complete Freund's adjuvant (CFA). We
      investigated three-dimensional distribution of nerve fibers in the TMJ disk using
      immunohistochemistry for protein gene product-9.5 (PGP-9.5) and calcitonin gene
      related peptide (CGRP) in naive and arthritic rats. To clarify the possible role
      of nerve growth factor (NGF) and its receptor on changes in peripheral
      innervation of the TMJ, the expressions of trkA and p75 receptor in trigeminal
      ganglia were examined. Although PGP-9.5 and CGRP immunoreactive (ir) fibers were
      seen in the peripheral part of the TMJ disk, they were not seen in its central
      part. The total length and the length density of PGP-9.5 ir and CGRP ir nerve
      fibers increased in arthritic rats. The innervation area of fibers proliferating
      in the rostro-medial part merged with that of fibers in the rostro-lateral part
      in the arthritic rats. In addition, the ratio of trkA- and p75-positive small-
      and medium-sized cells increased in trigeminal ganglia. It is assumed that
      increasing innervation of the TMJ disk may be important for the pathophysiology
      of TMJ pain. NGF and its receptors are likely involved in pathological changes of
      the TMJ disk.

PMID- 14575663
TI  - Electrical neuromodulation improves myocardial perfusion and ameliorates
      refractory angina pectoris in patients with syndrome X: fad or future?
AB  - At present, there is no reliable antianginal drug therapy for patients with
      cardiac syndrome X. Therefore, the effect of electrical neuromodulation on
      refractory angina pectoris and myocardial perfusion in cardiac syndrome X was
      assessed. Eight patients (aged 55+/-7 years) with heterogeneous myocardial
      perfusion and no esophageal abnormalities were included. The subjects were
      nonresponders to antianginal drug therapy. Angina pectoris attacks and myocardial
      perfusion dynamics were evaluated by positron emission tomography at baseline and
      following 4 weeks of (transcutaneous electrical nerve stimulation) TENS.
      Following TENS there was a reduction of angina pectoris episodes (baseline 20+/
      3, TENS 3+/-1; p=0.012), and short acting nitroglycerin intake per week (baseline
      10+/-3, TENS 2+/-1; p=0.008). The rate pressure product (mmHg min(-1)) during the
      cold pressor test (CPT) was reduced during TENS (baseline 12800+/-1200, TENS
      11500+/-900; p=0.02). Following TENS, the perfusion reserve ratio between rest
      and dipyridamole flow increased (baseline 1.59+/-0.15, TENS 1.90+/-0.11 ml min(
      1)x 100g; p=0.05). The coronary vascular resistance had a trend towards a
      reduction (baseline 0.96+/-0.04, TENS 0.85+/-0.06 mmHg min(-1)x 100 g/ml; p=0.06)
      during CPT. This observation may suggest that neurostimulation improves angina
      pectoris with a concomitant improvement of myocardial perfusion in cardiac
      syndrome X.

PMID- 14575664
TI  - Efficacy of spinal cord stimulation for neuropathic pain: assessment by
      abstinence.
AB  - Assessment of the efficacy of spinal cord stimulation (SCS) against neuropathic
      pain remains problematic. Some patients may underestimate this, as revealed by
      their reaction to stimulator malfunction. This study investigated whether
      abstinence from SCS would provide an indication of its effectiveness. Patients
      were invited to complete two brief questionnaires each day for 50 days including
      two periods of 14 days without stimulation. Pain level, sleep quality, activity
      level and drug intake were recorded. Of 75 patients thought to be using their
      stimulators, 12 did not respond to the invitation, eight had unresolved technical
      problems and one no longer needed SCS. Of the 54 remaining, 10 did not wish to be
      without SCS and 15 declined without giving a reason. Thus 29 agreed to take part
      but three then dropped out through illness and questionnaires were not received
      from 10. Ten returned completed questionnaires but failed to follow the protocol;
      five of these were unable to leave their stimulators off. Only six took part
      correctly. Twenty of the 29 had received a preliminary explanatory home visit and
      for nine this was done by telephone. The former produced a considerably higher
      yield. All six who completed the study correctly had statistically significantly
      lower pain scores during stimulation. Four had improved sleep but only one
      reduced his medication and none of the six increased their activity levels.
      Correlation with previous clinical assessments is discussed. It is concluded that
      the abstinence principle might provide a useful tool but its power is very
      methodology-dependent.

PMID- 14575665
TI  - Psychological responses to episodic chest pain.
AB  - Patients with chronic musculo-skeletal pain have been profiled as
      "dysfunctional", "interpersonally distressed" or "adaptive copers". The relevance
      of these for episodic visceral pain is unknown. Our aim was to replicate
      conceptually the taxonomy in patients with episodic visceral pain. Patients with
      chest pain and gastro-esophageal reflux disease (GERD; n=25), coronary artery
      (CAD; n=20), or with chest pain but without either reflux or coronary artery
      disease (non-cardiac chest pain--NCCP; n=23) were assessed using several standard
      affective and cognitive measures relevant to pain. Differences between the
      diagnostic groups were explored. K-means cluster analysis broadly replicated the
      three groups found in previous research but the "interpersonally distressed"
      group had few members. An additional cluster analysis suggested a more
      parsimonious solution for the sample was a two-cluster one, which approximated to
      the "adaptive coper" and "dysfunctional" profiles. Membership of both the three-
      and two-cluster profiles was not associated with membership of specific
      diagnostic category.

PMID- 14575666
TI  - Hypoalgesia to pressure pain in referred pain areas triggered by spatial
      summation of experimental muscle pain from unilateral or bilateral trapezius
      muscles.
AB  - Animal and human experimental studies have suggested the importance of spatial
      summation in the nociception processing and in the activation of descending
      inhibition. However, the relationship between the areas (size) of muscles
      stimulated and the recruitment of descending inhibition has not been addressed.
      Consequently, we tested whether bilateral versus unilateral injection of
      hypertonic saline into trapezius muscles caused hypoalgesia to pressure pain
      (pressure pain thresholds, PPTs) in the local pain areas (the trapezius muscles)
      and the referred pain areas (the posterolateral neck muscles). Two groups of
      volunteers participated. One group received a unilateral injection (one
      injection) and the other group bilateral injections (two injections). In the
      bilateral group, hypertonic saline was injected in one trapezius first, and 45 s
      later, while pain was still present from the first injection, a second injection
      was performed into the contralateral trapezius muscle. The saline-evoked time to
      maximal pain was significantly shorter after the second injection than after the
      first injection. More subjects developed referred pain after the bilateral
      compared with the unilateral injection. In the referred pain areas, the PPTs 7.5
      and 15 min after the second injection were significantly increased compared with
      the first injection, while no changes in the PPT were observed in local and
      referred pain areas after unilateral injection. This suggests that the induction
      of descending inhibition was triggered by spatial summation during the later
      phase of experimentally induced muscle pain. The present experimental model might
      be used for further investigation of descending inhibition related to the spatial
      characteristics of nociceptive stimuli in humans.

PMID- 14575667
TI  - Multi-modal induction and assessment of allodynia and hyperalgesia in the human
      oesophagus.
AB  - BACKGROUND AND AIMS: Experimental pain models based on single stimuli have to
      some degree limited visceral pain studies in humans. Hence, the aim of this study
      was to investigate the effect of multi-modal visceral pain stimuli of the
      oesophagus in healthy subjects before and after induction of visceral
      hyperalgesia. We used a multi-modal psychophysical assessment regime and a
      neurophysiological method (nociceptive reflex) for the characterisation of the
      experimentally induced hyperalgesia. METHODS: A probe for multi-modal (cold,
      warm, electrical, and mechanical) visceral stimulation was positioned in the
      lower part of the oesophagus in eleven healthy subjects. Mechanical stimuli were
      applied as distensions with a bag, which also had electrodes mounted for
      electrical stimulation. Thermal stimulation with temperatures from 0 to 60
      degrees C was applied with re-circulating water in the bag. To assess the
      interaction between visceral and somatic pathways, the nociceptive withdrawal
      reflex to electrical stimuli at the ankle was measured with and without
      simultaneous mechanical oesophageal distension to painful levels. Finally, the
      oesophageal sensitisation was induced by perfusion with hydrochloric acid.
      Multimodal responses (pain threshold, stimulus response function, size of
      nociceptive reflex, and referred pain areas) were assessed before and after the
      induced hyperalgesia. RESULTS: The multi-modal psychophysical responses and
      reflex sizes were assessed twice before sensitisation, and the parameters were
      reproducible. Sensitisation of the oesophagus resulted in hyperalgesia to
      electrical and mechanical stimuli (29 and 35% decrease in pain threshold) and
      allodynia to cold and warmth stimuli (11% increase in sensory rating). After
      sensitisation, the referred pain area to mechanical stimuli increased more than
      300% with a change in the localisation of the referred pain to all stimuli, and
      the amplitude of nociceptive reflex increased 100%, all indicating the presence
      of central hyperexcitability. CONCLUSIONS: Visceral hyperalgesia/allodynia can be
      induced experimentally and assessed quantitatively by the newly introduced multi
      modal psychophysical assessment approach. The significant changes of the
      experimentally evoked referred pain patterns and of the nociceptive reflex evoked
      from a distant somatic structure indicate that even short-lasting visceral
      hyperalgesia can generate generalised sensitisation.

PMID- 14575668
TI  - The natural course of chronic benign pain in childhood and adolescence: a two
      year population-based follow-up study.
AB  - STUDY OBJECTIVE: To assess the course of chronic benign pain in childhood and
      adolescence longitudinally.Setting. Cohort of children with chronic pain
      recruited from the open population. PATIENTS: A cohort of 987 children and
      adolescents aged 0-18 years with chronic pain (continuous or recurrent pain>3
      months), who were identified in a previous population-based prevalence study,
      were approached for a two-year follow-up study. Subjects were asked to keep a 3
      week diary on their pain and to fill out questionnaires about background factors,
      pain and pain-related consequences. This assessment was repeated annually for two
      years. RESULTS: At baseline, 254 subjects reported chronic benign pain; of these,
      124 (48%) and 77 (30%) subjects still experienced chronic benign pain at one-year
      and two-year follow-up, respectively. Except for the estimated pain intensity,
      which decreased marginally, pain remained stable over the follow-up period. Minor
      changes occurred in the consequences of pain; the main changes were a decrease of
      the impact of pain on the child's behavior, social functioning and use of health
      care. Subjects with persistent pain (9.4%) differed from those with non
      persistent pain in frequency, history and location of the pain, emotional
      problems and their mother's health. CONCLUSIONS: Chronic benign pain in childhood
      and adolescence is common, and seems to persist in a considerable proportion (30
      45%), although pain generally does not deteriorate over time.

PMID- 14575669
TI  - Moog M, Quinter J, Hall T, Zusman M. The late whiplash syndrome: a psychophysical
      study. Euro J Pain 2002;6:283-294.

PMID- 14575671
TI  - Comparative toxicity of chlorothalonil: Ceriodaphnia dubia and Pimephales
      promelas.
AB  - Chlorothalonil is a commonly used fungicide in rural and urban environments and
      can be incidentally introduced into aquatic systems through rainfall runoff or
      direct overspray and drift from aerial applications. Few studies have been
      published regarding risks to aquatic organisms exposed to chlorothalonil, so this
      study was performed to provide a first-order risk characterization for receiving
      system biota. Definitive laboratory toxicity tests were conducted with aqueous
      solutions of chlorothalonil and sentinel aquatic organisms (Ceriodaphnia dubia
      Richard and Pimephales promelas Rafinesque). P. promelas was more sensitive (7
      day potency=6.1% mortality/mug/L) than C. dubia (7-day potency=0.94%
      mortality/mug/L) to chlorothalonil exposures. All mortality of P. promelas and C.
      dubia resulting from these chlorothalonil exposures occurred within the first 96h
      and no sublethal effects (i.e., growth or reproduction) were detected under these
      experimental conditions following 7-day exposures.

PMID- 14575672
TI  - Demographic changes in Daphnia pulex (Leydig) after exposure to the insecticides
      spinosad and diazinon.
AB  - The toxicity of the natural insecticide spinosad was assessed against Daphnia
      pulex (Leydig) using a demographic approach. Data were also generated for the
      commonly used organophosphorus insecticide diazinon as a comparison. Exposure to
      spinosad led to a concentration-dependent decline in survival, birth rate (b),
      net reproductive rate (R(0)), and intrinsic rate of increase (r(m)). Population
      extinction (-r(m)) occurred after exposure to spinosad concentrations >10
      microg/L for 8 days. Exposure to increasing diazinon concentrations led to an
      initial increase in R(0) and r(m) followed by a sharp decline, with extinction
      occurring after exposure to >2 microg/L after 2 days. Based on concentrations of
      pesticide that caused population extinction, spinosad was five times less toxic
      than diazinon. The stable age distribution (after 65 days) of D. pulex changed
      after exposure to spinosad and diazinon. Increasing concentrations of spinosad
      resulted in a decrease in the percentages of individuals in the first juvenile
      and adult stages, increase in the third and fourth juvenile stages, and little or
      no change in the second juvenile and adolescent stages. Diazinon had a different
      effect on stable age distribution. Increasing concentrations of diazinon resulted
      in an increase in percentages of individuals in the first and second juvenile
      stages, little or no change in the third and fourth juvenile stages and
      adolescent stage, and a decrease in the adult stage. Although spinosad and
      diazinon are both neurotoxins, they have different modes of action and
      populations of D. pulex reacted differently to each pesticide. Results of this
      study indicate that spinosad is significantly less toxic than diazinon to D.
      pulex and because it is applied at lower concentrations than diazinon it should
      be less hazardous to this species.

PMID- 14575673
TI  - A study of the leachate toxicity of metal-containing solid wastes using Daphnia
      magna.
AB  - This paper examines the ecotoxicity of different actual inorganic wastes
      containing some potentially toxic metals commonly found in many industrial
      residues and the reduction in ecotoxicity obtained when the wastes are submitted
      to a solidification/stabilization process. The ecotoxicity was assessed as
      defined in the Spanish regulations on hazardous wastes, by means of the Daphnia
      magna Straus acute toxicity test applied to the toxicity characteristic leaching
      procedure (TCLP) waste leachate. On the basis of the EC50 values of the
      individual metals and the effect of the pH of the aqueous medium on D. magna, we
      have explored a method for estimating the toxicity of the TCLP waste leachate by
      calculating its EC50 value in the D. magna test. Although the method is only
      valid in cases in which a clear cause for the toxicity exists, the procedure
      described allows us to more completely explain the observed effects on the
      daphnids. The ecotoxicity of the residues after stabilization is less than that
      of the untreated waste, generally as a consequence of the reduction in metal
      leachability achieved by the immobilization treatment. The stabilization process
      was analyzed in terms of both the chemical and the ecotoxicological parameters,
      and the influence of leachate pH on the objectives of waste treatment is
      discussed.

PMID- 14575674
TI  - Stress protein response and catalase activity in freshwater planarian Dugesia
      (Girardia) schubarti exposed to copper.
AB  - The hsp60 expression pattern and catalase activity in the freshwater planarian
      Dugesia schubarti exposed to copper under laboratory conditions were
      investigated. In the hsp60 induction experiments, planarians were exposed to a
      range of copper concentrations (0-960 microgCu/L) for 4 or 24h, to concentrations
      of 50 or 100 microgCu/L for 2, 4, 8, and 24h at 19 degrees C, and to heat shock
      at 27 degrees C for 24h. The concentrations of hsp60 in whole-body homogenates
      were determined immunochemically by Western blotting. Stress protein induction
      was detected only after 24h treatment at 27 degrees C. The tissue concentration
      of hsp60 remained unaltered in Cu-exposed planarians under the experimental
      conditions used. Catalase activity was significantly induced at concentrations of
      40, 80, and 160 microgCu/L after 24h exposure. Our results suggest that catalase
      levels in planarians could represent biomarkers of interest for the estimation of
      copper effects in freshwater ecosystems.

PMID- 14575676
TI  - Toxicity of the Red Sea pufferfish Pleuranacanthus sceleratus "El-Karad".
AB  - The pufferfish Pleuranacanthus sceleratus (El-Karad) represents serious public
      health problems, because of its responsibility for many incidents in Egypt,
      especially in the Suez Gulf. In the present study, samples of this fish were
      collected monthly and the toxins were extracted from gonads, liver, digestive
      tract, muscles, and skin, then purified and identified using TLC and
      electrophoresis. The alkaline hydrolyzates of these toxins were also detected
      using UV absorption and GC-mass spectra of their trimethylsilyl derivatives.

PMID- 14575675
TI  - Yeast pheromone signaling pathway as a bioassay to assess the effect of chemicals
      on mammalian peptide hormones.
AB  - The intercellular pheromone signal transduction pathways involved in sexual
      reproduction in the yeast Saccharomyces cerevisiae constitute an extracellular
      network system involving cell surface receptors. The system is analogous to the
      signaling pathway of mammalian peptide hormones. The yeast mating pheromone alpha
      factor is homologous to mammalian gonadoliberins such as luteinizing hormone
      releasing hormone (LHRH). In this study, we used the yeast pheromone signaling
      pathway as a model system to evaluate the effect of industrial chemicals on
      mammalian peptide hormones. Haploid a- and alpha-cell types conjugate, using
      mating pheromones, to form diploid cells. However, in a cells treated with
      certain chemicals used in pesticides, fungicides, and industrial products (i.e.,
      TPN (CAS No. 1897-45-6), thiuram (CAS No. 137-26-8), captan (CAS No. 133-06-2),
      oxine-copper (CAS No. 10380-28-6), zineb (CAS No. 12122-67-7), and ziram (CAS No.
      137-30-4)) the induction of shmoo formation was suppressed even when commercial
      alpha-factor was added. The FUS1-lacZ gene, which is transcriptionally regulated
      by a pheromone, was transferred into yeast and the effects of TPN, captan, zineb,
      and ziram, under sublethal conditions, were investigated: beta-Galactosidase
      levels declined to levels similar to that of untreated control cells when in the
      absence of the alpha-factor. Furthermore, these chemicals influenced conjugation
      to alpha-cells, and mating efficiency declined as chemical concentration
      increased. Analysis of the yeast pheromone signaling pathway helps to establish
      chemical toxicity assay models for mammalian peptide signal transduction
      pathways.

PMID- 14575677
TI  - Long-term exposure effects in vitellogenin, sex hormones, and biotransformation
      enzymes in female carp in relation to a sewage treatment works.
AB  - In the present study, the estrogenic response in the reproductive cycle of female
      carp, Cyprinus carpio, in relation to a sewage treatment works (STWs) was
      measured as: alterations in plasmatic and hepatic vitellogenin (VTG) content,
      plasma levels of testosterone (T) and estradiol (E2), and effects on key enzymes
      of phases I and II biotransformation, ethoxyresorufin O-deethylase (EROD) and
      glutathione S-transferase (GST). Low plasma VTG content in females collected 4 km
      downstream of an effluent discharge suggested possible estrogenic disturbances;
      however, hepatic VTG content and sex hormone levels did not mirror this. In fact,
      E2 and T largely fluctuated among fish, with individual variations even greater
      than among sampling stations or periods. This suggests that at moderately
      polluted sites, biological variations of female carp and genetic particularities
      are prevalent. Hepatic biotransformation enzymes, such as EROD, increased with
      increasing water temperature while, in contrast, GST was maximal at the lowest
      water temperature.

PMID- 14575678
TI  - Acute and chronic aquatic toxicity structure-activity relationships for alcohol
      ethoxylates.
AB  - Acute and chronic toxicity tests using the cladoceran Daphnia magna were
      conducted on several alcohol ethoxylate surfactants. Exposure and homologue
      distributions were confirmed using specific analytical methods. These data were
      used to test currently available acute structure-activity relationships (SARs)
      and to develop a new chronic SAR to extrapolate test data to effluent or
      receiving water mixtures. Existing acute SARs adequately predicted the toxicity
      of these materials with an r(2) of 0.96 based on alkyl chain length and number of
      ethoxylates and 0.98 based on logK(ow). The additional chronic toxicity data
      allowed for development of a chronic SAR based on logK(ow) and produced an r(2)
      of 0.93. Slopes of new and published acute, chronic, and mesocosm SARs based on
      logK(ow) ranged from -0.61 to -0.87. These new data and refined SARs will assist
      in the toxicity prediction of mixtures in the environment.

PMID- 14575680
TI  - Bioaccumulation and toxicity of sediment associated herbicides (ioxynil,
      pendimethalin, and bentazone) in Lumbriculus variegatus (Oligochaeta) and
      Chironomus riparius (Insecta).
AB  - The benthic macroinvertebrates Lumbriculus variegatus and Chironomus riparius
      were used in toxicity and bioaccumulation tests to determine the toxic
      concentrations and accumulation potential of sediment associated herbicides. The
      tested chemicals were ioxynil, bentazone, and pendimethalin. The bioaccumulation
      tests with L. variegatus were performed in four different sediments, each having
      different characteristics. Water-only LC(50) tests were performed with both L.
      variegatus and C. riparius. A sublethal effect of model compounds in sediments
      was assessed by a C. riparius larvae growth-inhibition test. Of the model
      compounds, ioxynil appeared to be the most toxic, with LC(50) values 1.79 and
      2.79 mgL(-1) for L. variegatus and C. riparius, respectively. The LC(50) water
      concentrations for bentazone were 79.11 and 62.31 mgL(-1) for L. variegatus and
      C. riparius, respectively. Similarly, ioxynil revealed the highest
      bioaccumulation potential in bioaccumulation tests. The most important characters
      affecting chemical fate in the sediment seemed to be the organic matter content
      and the particle size fraction. The sediments with low organic material and
      coarse particle size consistently showed high bioaccumulation potential and vice
      versa. In C. riparius growth tests bentazone had a statistically significant
      effect on larval growth at sediment concentrations of 1160 and 4650 mgkg(-1)
      (P<0.05). It is noteworthy that standard deviations tend to be greater at high
      chemical concentrations, which addresses the fact that part of the individuals
      started to suffer. Ioxynil had an effect on the larval growth in other test
      sediment at the highest concentration (15.46 mgkg(-1)dw), in which head capsule
      length correlated with larval weight, decreasing toward higher exposure
      concentrations. The current results show the importance of sediment organic
      matter as a binding site of xenobiotics.

PMID- 14575679
TI  - Health hazards due to pollution of waters along the coast of Visakhapatnam, east
      coast of India.
AB  - Environmental pollution that renders waters along the coastline and beaches
      unsatisfactory for use by the general public has become a global health problem.
      This study was conducted to examine the effects of pollution of beach waters and
      sediment at seven selected locations receiving land drainage along a 45-km
      stretch of the east coast near Visakhapatnam, India. Pathogenic bacteria were
      identified using standard methods of culturing on selective media. The Pollution
      Index (PI) was determined as the ratio of fecal coliform/fecal streptococci.
      Protozoan cysts and helminth ova were also identified by microscopic examination
      of water after appropriate staining. The results suggested that the beach waters
      in Visakhapatnam are hygienically poor. A high PI of the water in Lawson's Bay
      indicated that the water was unsuitable even for noncontact recreation (boating,
      etc.). Pathogen densities dissipated considerably from the source to the low tide
      mark. Sediments had significantly higher bacterial and protozoan populations but
      pathogen concentrations were low except in heavily used areas. The general
      distribution pattern suggests that the nature of the sediment has a significant
      role in the retention of bacteria, protozoan cysts, and soil-transmitted
      helminths.

PMID- 14575681
TI  - Linking lysosomal biomarker and population responses in a field population of
      Aporrectodea caliginosa (Oligochaeta) exposed to the fungicide copper
      oxychloride.
AB  - The effects of the fungicide copper oxychloride on a field population of the
      earthworm Aporrectodea caliginosa were investigated. Changes were monitored in
      earthworm numbers and biomass, copper concentrations in soil and earthworms, and
      neutral red retention times (NRRTs) of coelomocytes. The aim was to establish
      whether the cellular responses could be linked to changes at the population
      level. Results indicated that there was a significant (P<0.05) impact on worm
      density and biomass on the treated plots 6 months after spraying with the
      fungicide stopped. NRRTs of treated earthworms were significantly lower after one
      spraying when earthworms had elevated concentrations of copper in their body
      tissues. Six months after spraying stopped, copper levels in both soil and
      earthworm tissues declined significantly, but the earthworm numbers and biomass
      were still significantly lower in the treated plots. This indicated that the
      effects of the copper oxychloride exposure manifested at a much later stage at
      the population level, than on NRRT. We conclude that the decrease in NRRTs, which
      preceded the decrease in both earthworm biomass and numbers, may have predictive
      value as a biomarker of impending population changes.

PMID- 14575682
TI  - Effects of a brassinosteroid analogue to mosquito larvae.
AB  - Many plant compounds are able to modulate herbivore growth and reproduction by
      directly interacting with steroid hormones systems. In insects, several classes
      of phytochemicals, including brassinosteroids and related substances, interfere
      with molting and reproduction. The effects of the molting-hormone antagonist
      pesticide DI-31, a brassinosteroid analogue, on Aedes aegypti mosquito larvae
      were tested in two different exposure scenarios. After static exposure of first
      instar larvae, the calculated NOEC, LOEC, and LC(50) values referenced to 19 d
      were 0.03, 0.036, and 0.04 mg/mL, respectively. Semistatic exposure of fourth
      instar larvae revealed them to be slightly less susceptible than the younger
      larvae (NOEC 0.03 mg/mL, LOEC 0.036 mg/mL, LC(50) 0.049 mg/mL referenced to 19
      days). In both cases mortality was immediate and larval development was retarded.
      This study suggests that A. aegypti could be a useful model for the detection of
      hormonally active substances such as DI-31.

PMID- 14575683
TI  - Endosulfan effects on muscle malate dehydrogenase of the freshwater catfish
      Clarias batrachus.
AB  - The effects of a sublethal concentration of an organochlorine pesticide
      endosulfan were investigated on crude and purified forms of cytoplasmic malate
      dehydrogenase (cMDH) and mitochondrial malate dehydrogenase (mMDH) in the muscle
      of the freshwater catfish Clarias batrachus. Endosulfan treatment reduced
      significantly the activity and the specific activity of cMDH and mMDH but had no
      effect on total cytoplasmic and mitochondrial protein contents. This indicates a
      decline in the efficiency of aerobic energy metabolism in endosulfan-treated
      fish. The polyacrylamide gel electrophoresis showed two distinct isoforms (C1 and
      C2) of cMDH and only one form of mMDH. The inhibition produced by endosulfan in
      vivo was of mixed noncompetitive/uncompetitive type for crude as well as purified
      cMDH and mMDH. However, in vitro inhibition was of simple noncompetitive and
      mixed competitive/noncompetitive type for purified cMDH and mMDH, respectively.
      Citrate was found to be an uncompetitive inhibitor of cMDH and mixed
      noncompetitive/uncompetitve inhibitor of mMDH. The inhibitory patterns were
      modulated by endosulfan. These results demonstrate inhibitory effects of
      endosulfan on skeletal muscle MDH of the freshwater catfish Clarias batrachus and
      inhibition effects are mediated through enzyme/substrate/endosulfan complexing.

PMID- 14575684
TI  - Eel ATPase activity as biomarker of thiobencarb exposure.
AB  - European eels (Anguilla anguilla) were exposed to a sublethal thiobencarb
      concentration of 0.22 mg/L in a flow-through system for 96 h. Mg(2+) and Na(+)
      K(+) adenosine triphosphatase (ATPase) activities were evaluated in gill and
      muscle tissues at 2, 12, 24, 48, 72, and 96 h of thiobencarb exposure. Gill
      ATPase activities were rapidly inhibited from 2h of contact onward. Highest
      inhibition was registered for Na(+), K(+)-ATPase (85%) from 2 to 12h. Both Mg(2+)
      and total ATPase were inhibited (>73%) during the first hours of toxicant
      exposure. At the end of the exposure period (96 h) ATPase activities were still
      different from those of the controls (>50%). Significant inhibition was detected
      in Na(+), K(+)-ATPase activity (80%) in muscle tissue after 2h and it was
      maintained over the entire exposure time. However, Mg(2+)-ATPase and total ATPase
      showed only perturbations after 2 h of exposure. Eels were exposed to 0.22 mg/L
      of thiobencarb for 96 h and then a recovery period in herbicide-free water was
      allowed for 192 h. Gill and muscle samples were removed at 8, 24, 72, 96, 144,
      and 192 h and ATPase activity was evaluated. Following 144 h of recovery, Mg(2+)-
      and Na(+), K(+)-ATPase activities, as well as total ATPase activity, in gills of
      those animals previously exposed to 0.22 mg/L of thiobencarb were still
      significantly different compared to controls. Thiobencarb seems to act to alter
      the ionic profiles. Since ion-dependent ATPases are known to regulate the influx
      and efflux of ions across the membrane to maintain the physiological requirements
      of the cells, the inhibition of Na(+), K(+)-ATPase probably induced
      osmoregulatory perturbations. On the other hand, thiobencarb exposure causes
      increases in the muscle water content of A. anguilla. The results indicated that
      water content increased significantly (>100% higher than the controls) during the
      first 24 h of exposure.

PMID- 14575685
TI  - Micronucleus test in freshwater fish species: an evaluation of its sensitivity
      for application in field surveys.
AB  - Brown trout, Salmo trutta, European eel, Anguilla anguilla, and European minnow,
      Phoxinus phoxinus, three fish species inhabiting European freshwater ecosystems,
      were evaluated for their use as in situ pollution biomarkers using the
      micronucleus test in renal erythrocytes. Experimental exposure (by immersion) to
      different concentrations of cyclophosphamide, colchicine, and cadmium showed that
      brown trout are more sensitive to the three compounds than minnows and eels. In
      situ surveys of wild freshwater ecosystems with different levels of pollution
      showed that minnows and eels living in polluted sites do not present higher
      micronuclei averages than those caught in clean rivers systems, whereas
      micronuclei are induced in brown trout inhabiting polluted sites. Our results
      demonstrated the suitability of brown trout for in situ biomonitoring of
      freshwater ecosystems as well as for laboratory tests using the micronucleus
      test.

PMID- 14575686
TI  - A novel hypothesis on the biochemical role of the Drosophila Yellow protein.
AB  - In Drosophila melanogaster, the protein product of the yellow gene is necessary
      for normal pigmentation and male sexual behavior. Although one of the best
      characterized loci from a genetic standpoint, the function of the Yellow protein
      in the development of either phenotype is unknown. Here I propose that Yellow
      acts as a growth factor- or hormone-like molecule in the development of
      pigmentation and sexual behavior, and discuss the consistency of this theory with
      experimental observations in flies and humans.

PMID- 14575687
TI  - Transcriptional activation of mouse mast cell protease-9 by microphthalmia
      associated transcription factor.
AB  - We explored transcriptional regulation of mouse mast cell protease-9 (mMCP-9),
      which is implicated in inflammation of the jejunum during helminth infections and
      tissue remodeling of the uterus during pregnancy. Transcription was positively
      regulated by microphthalmia-associated transcription factor (MITF), a member of
      the basic helix-loop-helix-leucine zipper family that binds to the E-box, a
      CANNTG sequence. The most significant segment for positive regulation by MITF was
      nt -183 to -177 of the mMCP-9 promoter, CATCATG, which bound MITF-M. In addition,
      not only other MITF isoforms but also TFE3, another member of the family,
      activated mMCP-9 transcription through this nucleotide sequence inserted one base
      within the E-box.

PMID- 14575688
TI  - Epitope mapping and evaluation of specificity of T-helper sites in four major
      antigenic peptides of chicken riboflavin carrier protein in outbred rats.
AB  - This paper reviews our studies on synthetic peptides spanning the major antigenic
      determinants of the chicken riboflavin carrier protein (RCP; 219 AA). These
      determinants are composed of residues 4-24 (YGC), 64-83 (CED), 130-147 (GEN), and
      200-219 (HAC) and function as minivaccines in terms of eliciting anti-peptide
      antibodies which recognize the native protein and are particularly promising
      contraceptive vaccine candidates. We have used 15-residue synthetic peptides to
      define short sequences involved in interaction with antibody and with T-cells. We
      have mapped the boundaries of T-cell epitopes of these peptides in outbred rats
      by immunizing the animals with each peptide and assaying the popliteal lymph node
      cell proliferation against a series of overlapping synthetic 15-mers covering the
      entire length of the individual peptides. The peptides YGC, GEN, and HAC
      harboured a single T-cell epitope each whereas the peptide CED exhibited bimodal
      response possessing two epitopes, one at N-terminus and the other at the C
      terminus. These studies provide insight into the way in which an immunogen is
      viewed by the immune system. In addition, preferential T-cell helper function for
      B cells recognizing unique determinants on the same molecule was demonstrated.
      This information helps in exploiting synthetic peptides in the construction of
      designer immunogens which have potential as candidate vaccines.

PMID- 14575689
TI  - 15-Deoxy-Delta(12,14)-prostaglandin J2 induces apoptosis through activation of
      the CHOP gene in HeLa cells.
AB  - Cyclopentenone prostaglandins (PGs) of the J series, which are produced by
      dehydration of PGD(2), have been reported to induce apoptosis in various cell
      lines. One of these cyclopentenone PGs, 15-deoxy-Delta(12,14)-prostaglandin J(2)
      (15-d-PGJ(2)), is the most potent inducer of apoptosis in the series, but the
      signaling pathways by which it induces apoptosis are poorly understood. We
      recently reported that cyclopentenone PGs accumulate in the endoplasmic reticulum
      (ER) and it has been shown that the transcription factor CHOP is induced by ER
      stresses and elicits apoptosis. In the present study we demonstrated that 15-d
      PGJ(2) induces CHOP mRNA/protein in HeLa cells via activation of the conserved
      regions in the CHOP promoter. Using several mutants of the CHOP promoter
      fragments, we found that two regions, CCAAT/enhancer-binding protein (C/EBP) site
      at -313 and ER-stress element (ERSE) at -93, are involved in activation of the
      CHOP gene by 15-d-PGJ(2). These results suggest that 15-d-PGJ(2) activates the
      CHOP promoter in two distinct pathways that could induce apoptosis of HeLa cells.

PMID- 14575690
TI  - PTH/PTH-related protein receptor interacts directly with Tctex-1 through its COOH
      terminus.
AB  - COOH-terminal cytoplasmic domains of G protein-coupled receptors (GPCRs) have
      been shown to carry determinants that control their cell surface localization,
      internalization, and recycling. In attempts to seek cellular proteins that
      mediate these processes of PTH/PTH-related protein receptor (PTHR), one of the
      class B GPCRs, we have found that Tctex-1, a 14kDa light chain of cytoplasmic
      dynein motor complex, interacts with the COOH-terminal tail of the receptor. A 34
      amino-acid stretch of the receptor responsible for binding to Tctex-1 has a
      bipartite structure consisting of a motif previously implicated in binding of
      some proteins to Tctex-1 and a putative new consensus sequence. Site-directed
      mutations or a 20-amino-acid deletion in the bipartite consensus binding sequence
      abolished the association of the PTHR COOH terminus with Tctex-1 in vitro. A GFP
      fused mutant PTHR impaired in binding to Tctex-1 expressed in MDCK cells showed a
      decreased rate of internalization in response to PTH compared to that of the wild
      type.

PMID- 14575691
TI  - Physical stress by magnetic force accelerates differentiation of human
      osteoblasts.
AB  - We examined the effect of magnetic force on differentiation of cultured human
      osteoblasts. Magnetic microparticles (MPs) were introduced into the cytoplasm of
      a human osteoblast cell line and the cells were cultured in a magnetic field (MF)
      in group MP-MF. Three groups of controls were used: cells without MPs were
      cultured out of MF (group C), cells without MPs were cultured in MF (group MF),
      and cells with MPs were cultured out of MF (group MP). The cells in group MP-MF
      became larger and were elongated along the axis of the magnetic poles. Appearance
      of alkaline phosphatase (AlPase) activity, formation of bone nodules, and calcium
      deposition were accelerated depending on the intensity of the magnetic field. It
      takes longer culture in the other three groups to exhibit these changes. Core
      binding factor A1 (Cbfa1: transcription factor for osteoblast differentiation)
      and osteocalcin (a bone-matrix protein involved in controlling osteogenesis) were
      expressed earlier or stronger in group MP-MF than the other groups. Then we
      compared phosphorylation of mitogen-activated protein kinase (MAPK) between group
      MP-MF and group C. Phosphorylation of p38(MAPK) (p38) was increased in group MP
      MF, while total p38 as well as total and phosphorylated forms of MAPK/ERK 1/2 and
      SAPK/JNK were not changed between the two groups. When a p38 inhibitor, SB
      203580, was added to the culture medium in group C, AlPase activity, formation of
      bone nodules, and calcium deposits were completely inhibited. On the other hand,
      they were inhibited only partially by a MAPK/ERK 1/2 inhibitor, U-0126. Based on
      these results, it is concluded that (1) osteoblast differentiation is accelerated
      by a magnetic force, (2) this acceleration is mainly attributed to the activation
      of p38 phosphorylation, and (3) the stimulus induced by a magnetic field offers a
      new approach to osteoblast differentiation.

PMID- 14575692
TI  - Mechanism of up-regulation of human Toll-like receptor 3 secondary to infection
      of measles virus-attenuated strains.
AB  - PolyI:C, a synthetic double-stranded (ds)RNA, and viruses act on cells to induce
      IFN-beta which is a key molecule for anti-viral response. Although dsRNA is a
      virus-specific signature and a ligand for human Toll-like receptor 3 (TLR3),
      largely uncharacterized multiple pathways associate virus-mediated IFN-beta
      induction. Here, we demonstrated that laboratory-adapted but not wild-type
      strains of measles virus (MV) up-regulated TLR3 expression both in dendritic
      cells and epithelial cell line A549. The kinetics experiments with the laboratory
      MV strain revealed that TLR3 was induced late compared to IFN-beta and required
      new protein synthesis. Furthermore, neutralizing antibodies against IFN-beta or
      IFNAR (Interferon-alpha/beta receptor) suppressed MV-induced TLR3 induction,
      indicating that type I IFN, IFN-alpha/beta, is critical for MV-mediated TLR3
      induction. Yet, a recently identified virus-inducible IFN, the IFN-lambda, did
      not contribute to TLR3 expression. A virus-responsive element that up-regulates
      TLR3 was identified in the TLR3-promoter region by reporter gene experiments. The
      ISRE, a recently reported site for IFN-beta induction, but not STAT binding site,
      located around -30bp of TLR3 promoter responded to MV to induce TLR3 expression.
      This further indicates the importance of type I IFN for TLR3 up-regulation in the
      case of viral infection. In HeLa and MRC5 cells, augmented production of IFN-beta
      was observed in response to dsRNA when TLR3 had been induced beforehand. Thus,
      the MV-induced expression of TLR3 may reflect amplified IFN production that plays
      a part in host defense to viral infection.

PMID- 14575693
TI  - 1-Methyl-4-phenylpyridinium-induced down-regulation of dopamine transporter
      function correlates with a reduction in dopamine transporter cell surface
      expression.
AB  - The mechanisms whereby 1-methyl-4-phenylpyridinium (MPP(+)) mediates cell death
      and Parkinsonism are still unclear. We have shown that dopamine transporter (DAT)
      is required for MPP(+)-mediated cytotoxicity in HEK-293 cells stably transfected
      with human DAT. Furthermore, MPP(+) produced a concentration- and time-dependent
      reduction in the uptake of [3H]dopamine. We observed a significant decrease in
      [3H]WIN 35428 binding in the intact cells with MPP(+). The saturation analysis of
      the [3H]WIN 35428 binding obtained from total membrane fractions revealed a
      decrease in the transporter density (B(max)) with an increase in the dissociation
      equilibrium constant (K(d)) after MPP(+) treatment. Furthermore, biotinylation
      assays confirmed that MPP(+) reduced both plasma membrane and intracellular DAT
      immunoreactivity. Taken together, these findings suggest that the reduction in
      cell surface DAT protein expression in response to MPP(+) may be a contributory
      factor in the down-regulation of DAT function while enhanced lysosomal
      degradation of DAT may signal events leading to cellular toxicity.

PMID- 14575694
TI  - The canonical Wnt pathway directly regulates NRSF/REST expression in chick spinal
      cord.
AB  - Neural precursor cells actively proliferate in the ventricular zone to self-renew
      the stem cell population, and in parallel, maintain their undifferentiated state.
      This progenitor pool generates postmitotic cells that migrate to the mantle layer
      and differentiate into mature neurons. The growth of these stem cells is strictly
      controlled by the canonical Wnt signaling cascade, in part mediated by the direct
      regulation of Cyclin D1, a critical regulator of cell cycle progression. Here, we
      report that the canonical Wnt pathway directly controls the expression of
      NRSF/REST. The Wnt-activated beta-catenin/TCF complex up-regulates this gene
      through a conserved element found in its exon 1a, a critical result obtained by a
      novel in ovo transcriptional assay. Hence, our data show that the canonical Wnt
      signaling cascade directly regulates the NRSF/REST and Cyclin D1 genes, thereby
      controlling the progenitor cells. In addition, we show that our in ovo
      transcription assay is a powerful way to analyze gene regulation in a natural in
      vivo context.

PMID- 14575695
TI  - Bcl-xL gene transfer protects the heart against ischemia/reperfusion injury.
AB  - Ischemia and reperfusion (I/R) injury causes the progression of cardiac
      dysfunction. The prevention of cardiomyocyte-loss due to I/R injury is important
      for the treatment of heart failure. Therefore, we employed antiapoptotic Bcl-xL
      protein to prevent I/R injury in the heart and evaluated the cardioprotective
      effect of Bcl-xL transduction by adenoviral vector (Adv) after I/R injury. Adv
      with Bcl-xL gene was injected in the rat heart 4 days prior to I/R. The
      prevention of cardiac performance-loss and the reduction of cardiac apoptosis,
      after 30min ischemia and 30min reperfusion of global I/R, were demonstrated in
      the heart with adenoviral Bcl-xL transduction. Also, significant reductions of
      the infarct size and serum creatine kinase levels were observed in the heart
      transduced with Bcl-xL gene compared with control after 30min ischemia and 24h
      reperfusion of the left anterior coronary artery. Thus, Bcl-xL may serve as a
      potential therapeutic tool for cardioprotection.

PMID- 14575696
TI  - Platelet factor 4 neutralizes heparan sulfate-enhanced antithrombin inactivation
      of factor Xa by preventing interaction(s) of enzyme with polysaccharide.
AB  - Platelet factor 4 (PF4) is a heparin-binding protein which exhibits anti-heparin
      activities through the inhibition of antithrombin (AT)-dependent reactions with
      the serine proteases thrombin and factor Xa. PF4 also neutralizes heparan sulfate
      (HS), a glycosaminoglycan (GAG) present on the surface of endothelial cells,
      thereby possibly modulating an anticoagulant response. Previous models of PF4
      mechanism did not distinguish whether PF4 causes steric hindrance of AT binding
      to fXa or of AT binding to the surface of the GAG chain. To shed light on the
      mechanism of PF4, studies of HS/heparin-catalyzed fXa inactivation by AT were
      undertaken. The results were consistent with PF4 directly interfering with AT
      binding to fXa rather than AT binding to the GAG chain, since PF4 did not prevent
      the heparin-dependent increase in AT intrinsic fluorescence. In fact, PF4
      mechanism was competitive with respect to AT and non-competitive with respect to
      fXa, suggesting inhibition of important regulatory/catalytic interactions of fXa
      with the polysaccharide. Altogether, the results suggested a model by which PF4
      bound to proximal (but distinct) sites to AT, resulting in steric interference of
      fXa binding to both polysaccharide and AT. It is proposed that PF4 inhibited the
      sequence of events recapitulated in the template mechanism describing heparin
      dependent inhibition of fXa.

PMID- 14575697
TI  - Identification of a SNARE protein required for vacuolar protein transport in
      Schizosaccharomyces pombe.
AB  - Intracellular vesicle trafficking is mediated by a set of SNARE proteins in
      eukaryotic cells. Several SNARE proteins are required for vacuolar protein
      transport and vacuolar biogenesis in Saccharomyces cerevisiae. A search of the
      Schizosaccharomyces pombe genome database revealed a total of 17 SNARE-related
      genes. Although no homologs of Vam3p, Nyv1p, and Vam7p have been found in S.
      pombe, we identified one SNARE-like protein that is homologous to S. cerevisiae
      Pep12p. However, the disruptants transport vacuolar hydrolase CPY (SpCPY) to the
      vacuole normally, suggesting that the Pep12 homolog is not required for vacuolar
      protein transport in S. pombe cells. To identify the SNARE protein(s) involved in
      Golgi-to-vacuole protein transport, we have deleted four SNARE homolog genes in
      S. pombe. SpCPY was significantly missorted to the cell surface on deletion of
      one of the SNARE proteins, Fsv1p (SPAC6F12.03c), with no apparent S. cerevisiae
      ortholog. In addition, sporulation, endocytosis, and in vivo vacuolar fusion
      appear to be normal in fsv1Delta cells. These results showed that Fsv1p is mainly
      involved in vesicle-mediated protein transport between the Golgi and vacuole in
      S. pombe cells.

PMID- 14575698
TI  - Human Kv1.6 current displays a C-type-like inactivation when re-expressed in cos
      7 cells.
AB  - The human Kv1.6K(+) channel was functionally re-expressed in COS-7 cells at
      different levels. Voltage-activated K(+) currents are recorded upon cell membrane
      depolarization independently of the level of Kv1.6 expression. The current
      acquires a fast inactivation when Kv1.6 expression is increased. Inactivation was
      not affected by divalent cations or by extracellular tetraethylammonium. We have
      characterized the inactivation properties in biophysical terms. The fraction of
      inactivated current and the kinetics of inactivation are increased as the cell
      becomes more depolarized. Inactivated current can be reactivated according to a
      bi-exponential function of time. Additional experiments indicate that Kv1.6
      inactivation properties are close to those of a conventional C-type inactivation.
      This work suggests that the concentration of Kv1.6 channel in the cell membrane
      strongly modulates the kinetic properties of Kv1.6-induced K(+) current. The
      physiological implications of these modifications are discussed.

PMID- 14575699
TI  - Antimicrobial peptides from scorpion venom induce Ca(2+) signaling in HL-60
      cells.
AB  - Parabutoporin (PP) and opistoporin 1 (OP1) are amphipathic alpha-helical
      antimicrobial peptides that were recently isolated from scorpion venom. In assays
      in which single granulocyte-like HL-60 cells as well as cells in suspension were
      used, both peptides were able to induce a reversible Ca(2+) release from
      intracellular stores and to increase Ca(2+) influx. Both effects could be clearly
      differentiated for OP1, inducing Ca(2+) release at lower concentrations. The
      Ca(2+) release was pertussis toxin-sensitive indicating the involvement of G
      proteins. Ca(2+) release depended on the stage of differentiation of the cells
      with undifferentiated cells being the most sensitive. Desensitization occurred
      with OP1. No cross-desensitization occurred between OP1 and the bacterial
      chemoattractant fMLP indicating the involvement of different types of receptors.
      Ca(2+) release by OP1 was found not to be mediated via interaction with the
      formyl peptide receptor-like 1. Although some of the results might favor a
      receptor-like interaction, the receptor involved could not be identified.

PMID- 14575700
TI  - Photofrin as a radiosensitizer in an in vitro cell survival assay.
AB  - Chemical modifiers (radiosensitizers) are used in order to increase the efficacy
      of radiotherapy. The use of Photodynamic Therapy for tumor treatment, especially
      with Photofrin II, is also known. At present, no chemical modifier has been found
      to act as a selective radiosensitizer. Experiments using several series of cell
      lines were performed; human bladder cancer cell line (RT4), colon adenocarcinoma
      cells (HT-29), and the glioblastoma cells (U-373 MG) were investigated, with and
      without incubation with Photofrin II, before irradiation. The irradiation was
      performed using doses ranging from 0 to 8Gy. Colony forming tests were applied to
      determine the efficiency of Photofrin II as a radiation sensitizer in comparison
      to irradiation alone. Two of the cell lines tested, cultures of the RT4 and U-373
      MG, treated with Photofrin II prior to radiation, showed cell survival lower than
      cultures untreated with Photofrin II but irradiated under identical conditions.
      For the HT-29 cells, the results did not differ between the two groups (with and
      without Photofrin). The results of this study showed that Photofrin II can act,
      under certain conditions as a tumor radiosensitizer.

PMID- 14575701
TI  - Molecular cloning and expression of novel fructosyl peptide oxidases and their
      application for the measurement of glycated protein.
AB  - Fructosyl peptide oxidases, enzymes that are active against a model compound of
      glycated hemoglobin, N(alpha)-fructosyl valyl-histidine, were characterized. To
      identify the primary structure of fructosyl peptide oxidases, we have prepared
      cDNA libraries from Eupenicillium terrenum ATCC18547 and Coniochaeta sp.
      NISL9330. The coding regions, both fungal fructosyl peptide oxidases consisting
      of 1314-bp, were obtained with degenerated primers based on the amino acid
      sequences and specific primers by 3(') and 5(') RACE (rapid amplification of cDNA
      ends). By their sequence similarities and substrate specificities, fructosyl
      peptide oxidases and their homologs could be categorized into two groups: (A)
      enzymes that preferably oxidize alpha-glycated molecules and (B) enzymes that
      preferably oxidize epsilon-glycated molecules. We showed that recombinant
      fructosyl peptide oxidases could be used to detect protease-treated fructosyl
      hexapeptide, a glycated peptide that is released from HbA(1C) by endoproteinase
      Glu-C, suggesting these enzymes could be useful for the enzymatic measurement of
      HbA(1C).

PMID- 14575702
TI  - Phosphoprotein phosphatase of Mycobacterium tuberculosis dephosphorylates serine
      threonine kinases PknA and PknB.
AB  - The regulation of cellular processes by the modulation of protein
      phosphorylation/dephosphorylation is fundamental to a large number of processes
      in living organisms. These processes are carried out by specific protein kinases
      and phosphatases. In this study, a previously uncharacterized gene (Rv0018c) of
      Mycobacterium tuberculosis, designated as mycobacterial Ser/Thr phosphatase
      (mstp), was cloned, expressed in Escherichia coli, and purified as a histidine
      tagged protein. Purified protein (Mstp) dephosphorylated the phosphorylated
      Ser/Thr residues of myelin basic protein (MBP), histone, and casein but failed to
      dephosphorylate phospho-tyrosine residue of these substrates, suggesting that
      this phosphatase is specific for Ser/Thr residues. It has been suggested that
      mstp is a part of a gene cluster that also includes two Ser/Thr kinases pknA and
      pknB. We show that Mstp is a trans-membrane protein that dephosphorylates
      phosphorylated PknA and PknB. Southern blot analysis revealed that mstp is absent
      in the fast growing saprophytes Mycobacterium smegmatis and Mycobacterium
      fortuitum. PknA has been shown, whereas PknB has been proposed to play a role in
      cell division. The presence of mstp in slow growing mycobacterial species, its
      trans-membrane localization, and ability to dephosphorylate phosphorylated PknA
      and PknB implicates that Mstp may play a role in regulating cell division in M.
      tuberculosis.

PMID- 14575703
TI  - Regulation and role of brush border-associated ERK1/2 in intestinal epithelial
      cells.
AB  - We have recently shown that elevated extracellular signal-regulated kinase (ERK)
      activities stimulate proliferation of intestinal cells whereas low sustained
      levels of ERK activities correlate with Gl arrest and are required for expression
      of several enterocyte differentiation proteins. In an attempt to clarify how
      ERK1/2 regulates intestinal differentiation, the present study assessed the
      subcellular distribution and regulation of ERK proteins and activities in
      differentiated enterocytes. We report that (1) ERK1/2 and their upstream
      modulators Ras, p85 (PI-3K), Rac1, and MEK1 are found in the brush border; (2)
      brush border-associated ERK1/2 are stimulated by EGF and feeding; (3)
      immunoblotting of proteins phosphorylated on SP/K motif suggests the presence of
      ERK substrates in the brush border, one of which could be actin; and (4)
      pharmacological inhibition of ERK alters microvilli architecture. Our results
      suggest that ERK may play important roles in the control of microvilli structure
      and possibly, in brush border-associated responses in differentiated intestinal
      epithelial cells.

PMID- 14575704
TI  - NF-kappaB-dependent regulation of tumor necrosis factor-alpha gene expression by
      CpG-oligodeoxynucleotides.
AB  - Immunostimulatory activities of synthetic oligodeoxynucleotides containing CpG
      motifs (CpG-ODNs) have gained attention as potentially useful immunotherapeutics.
      However, CpG-ODNs induce harmful and lethal shock effects because they greatly
      enhance the sequence-dependent induction of tumor necrosis factor-alpha (TNF
      alpha). We have shown that phosphorothioate-modified oligodeoxynucleotides (PS
      ODNs) of the CpG-ODN 1826 stimulate TNF-alpha gene expression, TNF-alpha promoter
      activity, IkappaB degradation, and NF-kappaB activation at higher levels compared
      with its phosphodiester ODN (PO-ODN). In contrast to the effects of CpG-ODN 1826,
      PS-ODN of the CpG-ODN 2006 showed lower stimulatory activities than its PO-ODN.
      Using transient transfection, it was found that myeloid differentiation protein
      (MyD88) and tumor necrosis factor receptor-associated factor 6 are commonly
      required for activation of the TNF-alpha promoter by various CpG-ODNs with
      different potencies. These results strongly suggest a possibility to optimally
      activate the innate immune responses by modulating the potency of CpG-ODNs via
      sequence rearrangement and phosphorothioate backbone modification.

PMID- 14575705
TI  - Molecular cloning and functional expression of nucleolar phospholipid
      hydroperoxide glutathione peroxidase in mammalian cells.
AB  - We cloned a full-length cDNA for phospholipid hydroperoxide glutathione
      peroxidase (PHGPx) including exon Ib from rat and mouse testis. The nuclear
      signal sequence of the N terminal of rat nuclear PHGPx possessed a different
      sequence from that previously reported for rat sperm nuclei GPx (SnGPx).
      Expression of this PHGPx-YFP (yellow fluorescent protein) fusion protein
      including a novel nuclear signal sequence was exclusively localized in nucleolus;
      although YFPs fused with only a novel nuclear signal sequence were distributed in
      the whole nucleus, indicating that preferential translocation of nucleolar PHGPx
      into nucleoli was required for the nuclear signal sequence and internal sequence
      of PHGPx. Low level expression of nucleolar PHGPx was detected in several
      tissues, but the expression of nucleolar PHGPx was extensively high in testis.
      Immunohistochemical analysis with anti-nucleolar PHGPx indicated that expression
      of nucleolar PHGPx was observed in the nucleoli in the spermatogonia,
      spermatocyte, and spermatid. Overexpression of 34kDa nucleolar PHGPx in RBL2H3
      cells significantly suppressed cell death induced by actinomycin D and
      doxorubicin that induced damage in the nucleolus. These results indicated that
      nucleolar PHGPx plays an important role in prevention of nucleolus from damage in
      mammalian cells.

PMID- 14575706
TI  - Functional characterization of a peroxisome proliferator response-element located
      in the intron 3 of rat peroxisomal thiolase B gene.
AB  - Expression of the rat peroxisomal 3-ketoacyl-CoA thiolase gene B is induced by
      peroxisome proliferators. Although a sequence element like a peroxisome
      proliferator-activated receptor (PPAR)-binding site is located in the promoter
      region of this gene, we previously found that this element is competent for the
      activation by hepatocyte nuclear factor-4, but not functional with PPARalpha. We
      describe here a new peroxisome proliferator-response element located in the
      intron 3 (+1422/+1434) that binds in vitro the PPARalpha/retinoid X receptor
      alpha heterodimer and confers the induction by PPARalpha in transfection assays.
      We propose a model of regulation of the rat thiolase B gene involving those
      elements in the promoter and intron 3.

PMID- 14575707
TI  - Induction of cell-cell detachment during glucose starvation through F-actin
      conversion by SNARK, the fourth member of the AMP-activated protein kinase
      catalytic subunit family.
AB  - SNARK, the fourth member of the AMPK catalytic subunit family, was originally
      identified in a rat kidney cDNA library, and in this study we isolated its human
      homologue. A BLAST search analysis using rat SNARK protein yielded a single high
      homology clone, DKFZp434J037, isolated from human testis, and since its
      hypothetical protein showed 84% homology to rat SNARK protein, we assumed
      DKFZp434J037 to be the human SNARK cDNA. The human SNARK cDNA is 3443bp long and
      encodes a 628 amino acid protein having an estimated molecular weight of 69kDa,
      and its chromosomal localization had been assigned to 1q32.1. The same as other
      members of AMPK catalytic subunit family, human SNARK showed AMP-dependent GST
      SAMS phosphorylation activity and enhanced HepG2 cell survival during glucose
      starvation. Human SNARK-overexpressing HepG2 cells (H/SNK) showed acute cell-cell
      detachment when exposed to glucose-free medium and the cell-cell detachment
      correlated well with the detection of G-actin. Deletion mutant analysis strongly
      suggested that the putative catalytic domain of SNARK is necessary for the cell
      cell detachment, and Western blotting analysis showed that phosphorylation of FAK
      and PKC, which were dramatically increased by glucose starvation in HepG2 cells,
      was markedly suppressed by SNARK.

PMID- 14575708
TI  - The mechanism of alphaB-crystallin gene expression by proteasome inhibition.
AB  - The mechanism of small heat shock protein/alphaB-crystallin gene expression by
      proteasome inhibition was investigated. Expression of alphaB-crystallin was
      induced efficiently only by proteasome inhibition and not by heat shock while
      expression of HSP27 was induced efficiently by both proteasome inhibition and
      heat shock. The promoter of the alphaB-crystallin gene contains two conserved
      heat shock elements, one located between -397 and -374 and the other between -57
      and -37, relative to the transcription start site. Electrophoretic mobility shift
      assay (EMSA) revealed that proteasome inhibition induces binding of heat shock
      factors to both heat shock elements in the alphaB-crystallin gene promoter.
      However, a transient transfection assay using deletion constructs of the alphaB
      crystallin gene promoter showed that the region between -373 and -58 plays an
      important role in promoter activity. These results indicate the presence of
      differential response mechanisms of alphaB-crystallin gene expression to
      proteasome inhibition and heat shock, and that the activation of heat shock
      elements is not sufficient for the efficient induction of the alphaB-crystallin
      gene by proteasome inhibition.

PMID- 14575709
TI  - Identification of functional nuclear export sequences in human sphingosine kinase
      1.
AB  - Sphingosine kinase (SPHK) is an enzyme that phosphorylates sphingosine to form
      sphingosine 1-phosphate (S1P). Human SPHK1 (hSPHK1) was localized predominantly
      in the cytoplasm when transiently expressed in Cos7 cells. In this study, we have
      found two functional nuclear export signal (NES) sequences in the middle region
      of hSPHK1. Deletion and mutagenesis studies revealed that the cytoplasmic
      localization of SPHK1 depends on its nuclear export, directed by the NES.
      Furthermore, upon treatment with leptomycin B, a specific inhibitor of the
      nuclear export receptor CRM1, a marked nuclear accumulation of hSPHK1 was
      observed, indicating that hSPHK1 shuttles between the cytoplasm and the nucleus.
      Our results provide the first evidence of the active nuclear export of SPHK1 and
      suggest it is mediated by a CRM1-dependent pathway.

PMID- 14575710
TI  - Roles of the insulin-like growth factor I receptor C-terminus in cellular
      radioresistance.
AB  - Available evidence suggests that insulin-like growth factor I receptor (IGF-IR)
      expression leads to increased cellular radioresistance. The most direct
      explanation of these findings predicts that IGF-IR is the source of survival
      signals in resistant cells. Mutational analysis revealed that protein truncated
      at amino acid 1245 in the C-terminus retained the ability of IGF-IR to confer
      radioresistance whereas point mutations at both Tyr-1250 and Tyr-1251 abrogated
      this effect using IGF-IR-deficient mouse embryo fibroblasts (R-) as a recipient.
      In cells expressing the latter mutant receptors, both phosphatidylinositol-3(')
      kinase (PI3-K) and mitogen-activated protein kinase (MAPK) signaling pathways
      remained intact, and addition of exogenous IGF-I could not change the
      radiosensitivity of these cells. Further analysis indicated that the abrogation
      of radioresistance required the presence of His-1293 and Lys-1294. These results
      suggest a novel regulatory role of the C-terminus of IGF-IR in mediating cellular
      radioresistance that may be independent of survival signals transmitted through
      this receptor.

PMID- 14575711
TI  - Enhanced cell attachment and osteoblastic activity by P-15 peptide-coated matrix
      in hydrogels.
AB  - The cells in bone grow on a composite matrix made up of mineral and organic
      (mainly type-I collagen) components. In this study, anorganic bone mineral (ABM)
      particles were coated with a cell-binding domain of type-I collagen (P-15
      peptide) to mimic the bone matrix components and suspended in injectable
      hyaluronate (Hy) hydrogels. The ABM/P-15/Hy was compared to ABM/Hy-the same
      matrix without P-15 peptide. Osteoblast-like HOS cells migrated through the
      hydrogels around ABM/P-15 or ABM particles; however, more cells adhered to ABM/P
      15/Hy particles, and the cells formed better surface coverage and had more stress
      fibers on ABM/P-15/Hy. HOS cells cultured on ABM/P-15/Hy had increased osteogenic
      gene expression for alkaline phosphatase and bone morphogenetic proteins, and
      deposited more mineralized matrix. Studies with two different hydrogels
      (carboxymethylcellulose and sodium alginate) showed similar enhanced cell
      attachment and mineralization. The studies suggest that the ABM/P-15 in hydrogels
      can be used as an injectable biomimetic matrix to facilitate bone repair.

PMID- 14575712
TI  - ZD7288 inhibits low-threshold Ca(2+) channel activity and regulates sperm
      function.
AB  - In this study, ZD7288, a blocker of hyperpolarization-activated and cyclic
      nucleotide-gated (HCN) channels, has been found to inhibit the mouse sperm
      acrosome reaction (AR). HCN channels have not yet been either recorded or
      implicated in mouse sperm AR, but low-threshold (T-type) Ca(2+) channels have.
      Interestingly, ZD7288 blocked native T-type Ca(2+) currents in mouse
      spermatogenic cells with an IC(50) of about 100 microM. This blockade was more
      effective at voltages producing low levels of inactivation, suggesting a
      differential affinity of ZD7288 for different channel conformations. Furthermore,
      ZD7288 inhibited all cloned T-type but not high-threshold N-type channels
      heterologously expressed in HEK-293 cells. Our results further support the role
      of T-type Ca(2+) channels in the mouse sperm AR.

PMID- 14575713
TI  - Crystal structure of Salmonella typhimurium 2-methylisocitrate lyase (PrpB) and
      its complex with pyruvate and Mg(2+).
AB  - Propionate metabolism in Salmonella typhimurium occurs via 2-methylcitric acid
      cycle. The last step of this cycle, the cleavage of 2-methylisocitrate to
      succinate and pyruvate, is catalysed by 2-methylisocitrate lyase (PrpB). Here we
      report the X-ray crystal structure of the native and the pyruvate/Mg(2+) bound
      PrpB from S. typhimurium, determined at 2.1 and 2.3A, respectively. The structure
      closely resembles that of the Escherichia coli enzyme. Unlike the E. coli PrpB,
      Mg(2+) could not be located in the native Salmonella PrpB. Only in pyruvate bound
      PrpB structure, Mg(2+) was found coordinated with pyruvate. Binding of pyruvate
      to PrpB seems to induce movement of the Mg(2+) by 2.5A from its position found in
      E. coli native PrpB. In both the native enzyme and pyruvate/Mg(2+) bound forms,
      the active site loop is completely disordered. Examination of the pocket in which
      pyruvate and glyoxalate bind to 2-methylisocitrate lyase and isocitrate lyase,
      respectively, reveals plausible rationale for different substrate specificities
      of these two enzymes. Structural similarities in substrate and metal atom binding
      site as well as presence of similar residues in the active site suggest possible
      similarities in the reaction mechanism.

PMID- 14575714
TI  - Expression of functional mu-opioid receptors in human osteoarthritic cartilage
      and chondrocytes.
AB  - There is evidence of effects of morphine on cell proliferation and intraarticular
      morphine produces analgesia and has an anti-inflammatory effect in chronic
      arthritis. The effects of opioids are mediated through the G-protein-coupled
      receptors affecting the cAMP pathway. We demonstrated that human osteoarthritic
      cartilage and cultured chondrocytes possess the mu-opioid receptor. The presence
      of the receptor was shown by immunodetection, polymerase chain reaction, and
      Western blotting. Stimulation of chondrocytes with beta-endorphin resulted in
      decreased phosphorylation of the transcription factor cAMP responsive element
      binding protein (CREB). The effect was reversed by naltrexone. The obtained
      results indicate that in human articular chondrocytes opioids affect, via the mu
      opioid receptor, the transcription factor CREB which in turn can cause subsequent
      changes in gene expression.

PMID- 14575715
TI  - Structural requirements for the inhibitory action of the CD9 large extracellular
      domain in sperm/oocyte binding and fusion.
AB  - CD9 has been shown to be essential for sperm/oocyte fusion in mice, the only non
      redundant role found for a member of the tetraspanin family. CD9 can act in cis,
      reconstituting sperm/oocyte fusion when ectopically expressed in oocytes from CD9
      null mice, or in trans, inhibiting sperm fusion when the large extracellular
      domain (LED) is added to CD9-positive oocytes as a soluble protein. In contrast
      to cis inhibition, the structural requirements of the trans inhibition by soluble
      CD9 LED are unknown. Here we show that human CD9 LED is as potent an inhibitor as
      mouse CD9 LED in mouse sperm/oocyte fusion assays and that CD9 LED can also
      inhibit sperm/oocyte binding. The two disulphide bridges that define membership
      of the tetraspanin family are critical for structure and function of human CD9
      LED and mutation of a pentapeptide sequence in the hypervariable region further
      defines the critical region for trans inhibition.

PMID- 14575716
TI  - Identification of isochore boundaries in the human genome using the technique of
      wavelet multiresolution analysis.
AB  - Incorporated with the Z curve method, the technique of wavelet multiresolution
      (also known as multiscale) analysis has been proposed to identify the boundaries
      of isochores in the human genome. The human MHC sequence and the longest contigs
      of human chromosomes 21 and 22 are used as examples. The boundary between the
      isochores of Class III and Class II in the MHC sequence has been detected and
      found to be situated at the position 2,490,368bp. This result is in good
      agreement with the experimental evidence. An isochore with a length of about 7Mb
      in chromosome 21 has been identified and found to be gene- and Alu-poor. We have
      also found that the G+C content of chromosome 21 is more homogeneous than that of
      chromosome 22. Compared with the window-based methods, the present method has the
      highest resolution for identifying the boundaries of isochores, even at a scale
      of single base. Compared with the entropic segmentation method, the present
      method has the merits of more intuitiveness and less calculations. The important
      conclusion drawn in this study is that the segmentation points, at which the G+C
      content undergoes relatively dramatic changes, do exist in the human genome.
      These 'singularity' points may be considered to be candidates of isochore
      boundaries in the human genome. The method presented is a general one and can be
      used to analyze any other genomes.

PMID- 14575717
TI  - Genetic attachment of undecane peptides to ovomucoid third domain can suppress
      the production of specific IgG and IgE antibodies.
AB  - An undecane peptide (Gly-Ser-Pro-Gly-Ile-Pro-Gly-Ser-Thr-Gly-Met) was genetically
      attached to the N-terminus of ovomucoid third domain (DIII) to investigate
      structural characteristics of linear IgE and IgG (B cell) epitopes in DIII with
      respect to modulation of the immune response towards antigenicity and
      allergenicity. Balb/c mice were sensitized with native DIII, wild type
      recombinant DIII, and recombinant modified DIII containing the extra amino acid
      stretch. The immune responses to the antigens were compared using enzyme-linked
      immunosorbent assay. Interestingly, specific IgE and IgG levels were suppressed
      when the modified DIII was used as antigen. This was further confirmed by
      synthesizing immunodominant IgE and IgG epitopes of DIII on cellulose acetate
      membrane (SPOTs) and probing them with antibodies raised against DIII antigens.
      Anti-recombinant wild type DIII anti-serum showed strong binding activities to
      immunodominant IgE and IgG epitopes, while anti-modified DIII serum did not show
      any significant binding to the IgE and IgG epitopes. Thus, it is clearly
      demonstrated that the amino acid stretch in DIII is masking the immune reactive
      epitope. Genetical attachment of peptides into DIII was found to be effective in
      reducing the production of specific IgE and IgG antibodies in mice.

PMID- 14575718
TI  - Acid induced unfolding of anthrax protective antigen.
AB  - Acidic pH plays an important role in the membrane insertion of protective antigen
      (PA) of anthrax toxin leading to the translocation of the catalytic moieties. The
      structural transitions occurring in PA as a consequence of change in pH were
      investigated by fluorescence and circular dichroism measurements. Our studies
      revealed the presence of two intermediates on-pathway of acid induced unfolding;
      one at pH 2.0 and other at pH 4-5. Intrinsic fluorescence measurements of these
      intermediates showed a red shift in the wavelength of emission maximum with a
      concomitant decrease in fluorescence intensity, indicative of the exposure of
      tryptophan residues to the bulk solvent. Furthermore, no significant change was
      seen in the secondary structure of PA at a pH of 2.0, as indicated by far UV-CD
      spectra. The low pH intermediate of PA was characterized using the hydrophobic
      dye, 8-anilino-1-naphthalenesulfonate, and was found to have properties similar
      to those of a molten globule state.

PMID- 14575719
TI  - HNF1alpha upregulates the human AE2 anion exchanger gene (SLC4A2) from an
      alternate promoter.
AB  - The human AE2 gene (SLC4A2) is transcribed in a widespread fashion from the
      upstream promoter, the resultant full-length transcript AE2a being encountered in
      most tissues. Moreover, alternate promoter sequences within intron 2 may drive
      tissue-restricted expression of variants AE2b(1) and AE2b(2), mainly in liver and
      kidney. AE2b(2) proximal promoter sequences are highly active in transfected
      liver-derived HepG2 cells and contain an HNF1 motif. Mutation-disruption of this
      motif dramatically decreased alternate promoter activity in HepG2 cells but not
      in prostate-derived PC-3 cells. Electromobility shift and supershift assays
      indicated that HNF1alpha from HepG2 nuclear extracts binds the HNF1 sequence.
      Transactivation studies in PC-3 cells showed enhanced activity of the wild-type
      construct upon cotransfection with an HNF1alpha expression plasmid, while
      activity of the HNF1-mutated construct remained unaffected. Since liver AE2 is
      putatively involved in the biliary secretion of bicarbonate, HNF1alpha may have a
      role in increasing bicarbonate secretion in response to certain stimuli.

PMID- 14575720
TI  - Action of Bauhinia bauhinioides synthetic peptides on serine proteinases.
AB  - The kallikrein inhibitor found in Bauhinia bauhinioides seeds (BbKI) differs from
      classical Kunitz plant inhibitors in the lack of disulfide bridges in its
      structure [Biochim. Biophys. Acta 1477 (2000) 64-74]. In this study, we examined
      whether structural properties may be involved in inhibitory specificity and, if
      so, whether those properties might be useful tools in designing compounds that
      interfere with enzyme activity. Peptides structurally related to the BbKI
      (RPGLPVRFESPLRINIIKE-NH(2)) reactive site were synthesized by solid-phase method
      and assayed for serine proteinase activity. The peptides RPGLPVRFESPLRINIIKE
      NH(2), RPGLPVRFESPL-NH(2), and GLPVRFES-NH(2) were efficient tissue kallikrein
      inhibitors, with I(50) values of 0.54 microM, 0.87 microM, and 0.5mM,
      respectively. The lasting inhibitory effect was observed in incubation periods of
      up to 120 min. None of the studied peptides interfere with the activity of
      thrombin, factor Xa or trypsin, although the native protein BbKI is a potent
      trypsin inhibitor.

PMID- 14575721
TI  - Adeno-associated viral vectors for retinal gene transfer.
AB  - Vectors derived from adeno-associated viruses (AAV) represent a promising tool
      for retinal gene transfer in pre-clinical and clinical settings. AAV vectors
      efficiently transduce dividing and non-dividing cells, escape cellular immunity
      and result in long-non-term transduction. In addition, they may be targeted to
      specific retinal cell types by taking advantage of surface proteins from various
      AAV serotypes thus limiting transfer of therapeutic genes to those cells
      requiring correction. This review will provide an overview of the properties of
      AAV vectors followed by a detailed report of their use in retinal gene transfer
      for mendelian and non-mendelian disorders.

PMID- 14575722
TI  - Retinal and choroidal angiogenesis: pathophysiology and strategies for
      inhibition.
AB  - Retinal angiogenesis and choroidal angiogenesis are major causes of vision loss,
      and the pathogenesis of this angiogenesis process is still uncertain. However,
      several key steps of the angiogenic cascade have been elucidated. In retinal
      angiogenesis, hypoxia is the initial stimulus that causes up regulation of growth
      factors, integrins and proteinases, which result in endothelial cell
      proliferation and migration that are critical steps in this process. Once the
      endothelial tube is formed from the existing blood vessels, maturation starts
      with recruitment of mural cell precursors and formation of the basement membrane.
      Normally, there is a tight balance between angiogenic factors and endogenous
      angiogenesis inhibitors that help to keep the angiogenic process under control.
      Although the steps of choroidal angiogenesis seem to be similar to those of
      retinal angiogenesis, there are some major differences between these two
      processes. Several anti-angiogenic approaches are being developed in animal
      models to prevent ocular angiogenesis by blocking the key steps of the angiogenic
      cascade. Based on these pre-clinical studies, several anti-angiogenic clinical
      trials are ongoing in patients with diabetic retinopathy and age-related macular
      degeneration. This review discusses the pathogenesis of retinal and choroidal
      angiogenesis, and alternative pharmacological approaches to inhibit angiogenesis
      in ocular diseases.

PMID- 14575723
TI  - Mechanical properties of the human lens capsule.
AB  - The human lens capsule has recently been the subject of much attention in an
      attempt to understand its physiological function in relation to the accommodative
      function, its functional reserve in the elderly population, and its potential in
      relation to cataract surgery. This overview presents our current knowledge of the
      mechanical properties of the human lens capsule, discussed on basis of its
      structure and its role in accommodation and cataract surgery.

PMID- 14575724
TI  - The effects of antiglaucoma and systemic medications on ocular blood flow.
AB  - Based on the body of evidence implicating ocular blood flow disturbances in the
      pathogenesis of glaucoma, there is great interest in the investigation of the
      effects of antiglaucoma drugs and systemic medications on the various ocular
      vascular beds. The primary aim of this article was to review the current data
      available on the effects of antiglaucoma drugs and systemic medications on ocular
      blood flow. We performed a literature search in November 2002, which consisted of
      a textword search in MEDLINE for the years 1968-2002. The results of this review
      suggest that there is a severe lack of well-designed long-term studies
      investigating the effects of antiglaucoma and systemic medications on ocular
      blood flow in glaucomatous patients. However, among the 136 articles dealing with
      the effect of antiglaucoma drugs on ocular blood flow, only 36 (26.5%)
      investigated the effects of medications on glaucoma patients. Among these 36
      articles, only 3 (8.3%) were long-term studies, and only 16 (44.4%) were double
      masked, randomized, prospective trials. Among the 33 articles describing the
      effects of systemic medications on ocular blood flow, only 11 (33.3%)
      investigated glaucoma patients, of which only one (9.1%) was a double-masked,
      randomized, prospective trial. Based on this preliminary data, we would intimate
      that few antiglaucoma medications have the potential to directly improve ocular
      blood flow. Unoprostone appears to have a reproducible antiendothelin-1 effect,
      betaxolol may exert a calcium-channel blocker action, apraclonidine consistently
      leads to anterior segment vasoconstriction, and carbonic anhydrase inhibitors
      seem to accelerate the retinal circulation. Longitudinal, prospective, randomized
      trials are needed to investigate the effects of vasoactive substances with no
      hypotensive effect on the progression of glaucoma.

PMID- 14575725
TI  - Serum melatonin and urinary 6-sulfatoxymelatonin in major depression.
AB  - In this study, serum melatonin and urinary 6-sulfatoxymelatonin (aMT6s) were
      measured in 14 major depressive inpatients, compared to 14 matched controls
      according to age, gender, season and hormonal treatment in women. Moreover, the
      relationship between serum melatonin and urinary aMT6s levels was analysed in the
      two groups. Results indicated that the two groups of subjects showed a clear
      melatonin rhythm without significant difference in the mean level of melatonin or
      aMT6s, in the area under the curve of melatonin or in the melatonin peak.
      However, the time of the nocturnal melatonin peak secretion was significantly
      delayed in depressive subjects as compared to healthy controls. Moreover, the
      depressed patients showed urinary aMT6s concentrations enhanced in the morning
      compared to night time levels, while these concentrations were lowered from the
      night to the morning in the control group. These results suggest that the
      melatonin production is phase-shifted in major depression.

PMID- 14575726
TI  - Cytokine mRNA expression patterns in the disease course of female adolescents
      with anorexia nervosa.
AB  - Anorexia nervosa (AN) is a serious eating disorder characterized by extreme
      weight loss and abnormalities of the neuroendocrine and immune systems. Cytokines
      have been discussed to be involved in the pathomechanisms underlying cachexia.
      Therefore our study aimed at examining the mRNA expression pattern of tumor
      necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin-6
      (IL-6) and interleukin-10 (IL-10) in whole blood of 11 female AN patients and 10
      age and sex matched normal weight control subjects using a sensitive quantitative
      polymerase chain reaction (PCR) method. We found a significant increase in TNF
      alpha and IL-6 mRNA expression in anorectic patients at admission (mean BMI 14.8
      +/- 1.3) when compared to controls. During follow-up, the expression of TNF-alpha
      mRNA remained significantly higher in formerly anorectic patients (mean BMI 18.7
      +/- 0.5) while IL-6 mRNA expression decreased. We interpret our results as
      suggesting that TNF-alpha may contribute to metabolic abnormalities in anorexia
      nervosa even after goal BMI is achieved.

PMID- 14575727
TI  - Triphasic oral contraceptive treatment alters the behavior and neurobiology of
      female cynomolgus monkeys.
AB  - Oral contraceptives (OCs) are the most widely prescribed and effective of the
      reversible contraceptive methods. In addition to inhibiting ovulation, OCs alter
      central nervous system function in women; however, methodological problems have
      prevented clear human studies. Thus, in this experiment we investigated the
      effects of OC treatment on behavior, hypothalamic- pituitary-adrenal axis
      function and the central nervous system in 75 adult female cynomolgus monkeys
      (Macaca fascicularis) housed in social groups of four to five monkeys per pen.
      Monkey social groups were randomly divided into either a control or an OC
      treatment group which was administered a clinically prescribed OC (Triphasil(R),
      levonorgestrel and ethinyl estradiol tablets) for 2 years. OC treatment increased
      the frequency of contact aggression received, time spent in locomotion, and
      sitting close to another animal, and decreased time spent fearfully scanning. OC
      treatment decreased heart rate, increased activity levels, and increased baseline
      cortisol concentrations and the cortisol response to adrenocorticotropin compared
      to control animals. OC treatment decreased the prolactin response to fenfluramine
      suggesting decreased serotonergic activity. These results suggest that this
      triphasic OC disrupts social behavior, hypothalamic-pituitary-adrenal axis
      regulation and the underlying central nervous system function.

PMID- 14575728
TI  - The effects of vasopressin on human facial responses related to social
      communication.
AB  - Arginine vasopressin (AVP) and arginine vasotocin (AVT) influence social
      behaviors in a number of species from diverse taxonomic groups, therefore
      suggesting a conservation of social functions for these homologous neuropeptides
      during vertebrate evolution. However, whether or not AVP has the ability to
      directly influence social behavior in humans has not yet been determined. Because
      influences of AVT/AVP on behaviors related to social communication, particularly
      in aggressive contexts, are among the most consistently observed across species
      from diverse vertebrate groups, the present study was designed to determine if
      AVP administration would influence cognitive, autonomic and/or somatic responses
      to species-specific social stimuli important for agonistic communication in
      humans. Specifically, we tested the effects of intranasal AVP administration on
      attention towards emotionally expressive facial expressions, as well as on heart
      rate (HR), skin conductance (SC) and corrugator supercilii electromyograms
      (corrugator EMG) in response to these social stimuli. AVP did not affect
      attention toward, nor autonomic arousal in response to, emotionally neutral,
      happy or angry facial expressions, but it did selectively enhance the corrugator
      EMG responses evoked by emotionally neutral facial expressions, making them
      similar in magnitude to responses evoked by angry facial expressions in control
      subjects. Because this muscle group is involved in agonistic communication, these
      results suggest that AVP may influence aggression in human males by biasing
      individuals to respond to emotionally ambiguous social stimuli as if they were
      threatening/aggressive.

PMID- 14575729
TI  - Musculo-skeletal pain, psychological distress, and hormones during the menopausal
      transition.
AB  - OBJECTIVE: To investigate the relationship between sex hormones (estradiol,
      testosterone, androstendione, DHEA-S) and prolactin on one hand and musculo
      skeletal pain and psychological distress on the other during the menopausal
      transition. METHOD: Fifty-seven regularly menstruating women, who were studied
      over five consecutive years, who reached menopause before the fifth assessment,
      and did not use hormone replacement therapy were included in the study. Hormones
      were sampled and a questionnaire including questions on psychological distress
      and musculo-skeletal pain were administered at the five points of assessment.
      Data on last year before menopause (T1), first (T2) and second (T3) year after
      menopause are reported. RESULTS: DHEA-S, but neither testosterone nor
      androstendione, was inversely related to distress and pain. Pain contributed to
      the variance of DHEA-S over the menopausal transition, whereas DHEA-S levels did
      not predict pain or distress when baseline levels were controlled for. Prolactin
      was at T1 and T2 positively associated with distress and at T2 positively
      associated with musculo-skeletal pain. Musculo-skeletal pain pre-menopause was
      significantly related to estradiol. CONCLUSION: DHEA-S was negatively associated,
      and prolactin positively associated with musculo-skeletal pain and psychological
      distress. Whereas post-menopause DHEA-S levels were influenced by pain scores, no
      significant effect of pre-menopause hormones on post-menopause pain and distress
      was found.

PMID- 14575730
TI  - Relationship between testosterone supplementation and insulin-like growth factor
      I levels and cognition in healthy older men.
AB  - BACKGROUND: Our laboratory has previously reported that testosterone (T)
      administration to older men significantly improves cognitive function. This study
      examined potential changes in insulin-like growth factor (IGF) IGF-I, IGF-II and
      IGF-related binding proteins in response to T administration in older men and
      their relationship to cognitive functioning. METHODS: Twenty-five healthy
      community dwelling volunteers, ranging in age from 50-80 years were randomized to
      receive weekly intra-muscular (i.m.) injections of either 100 mg T enanthate or
      placebo (saline) for 6 weeks. Serum hormone levels and cognitive functioning was
      assessed at baseline and twice during treatment. RESULTS: Significant positive
      associations between IGF-I and IGF-II and spatial memory, spatial reasoning, and
      verbal fluency were observed after 6 weeks of T administration. Increased serum T
      levels from treatment were positively associated with improvement in spatial
      reasoning performance, whereas estradiol was associated with a decline in divided
      attention performance. Serum IGF-I, IGF-II and IGFBPs did not change in response
      to T treatment. CONCLUSIONS: Our results suggest that T, estradiol and IGF-I may
      have independent and selective effects on cognitive functioning. Positive
      associations between T levels and cognition are consistent with an effect of
      androgen treatment, whereas positive associations between IGF-I levels and
      cognition are reflective of a relationship between endogenous IGF-I levels and
      cognition.

PMID- 14575731
TI  - HPA axis responses to laboratory psychosocial stress in healthy elderly adults,
      younger adults, and children: impact of age and gender.
AB  - Data from five independent studies were reanalyzed in order to investigate the
      impact of age and gender on HPA axis responses to an acute psychosocial
      laboratory stress task. The total sample consisted of 102 healthy subjects with
      30 older adults (mean age: 67.3 y), 41 young adults (mean age: 23.5 y), and 31
      children (mean age: 12.1 y). All participants were exposed to the Trier Social
      Stress Test (TSST). The stress protocol caused highly significant ACTH and total
      plasma cortisol responses in older and younger male and female adults (all
      p<0.0001) as well as salivary free cortisol responses in all six age and gender
      groups (all p<0.0001). Three-way ANOVAs for repeated measurement were applied to
      investigate the impact of age and gender on ACTH and cortisol responses. Results
      showed that the ACTH response to stress was higher in younger adults compared to
      older adults (main effect: p=0.009, interaction: p=0.06). Post hoc analyses
      revealed that there was no age effect in the subgroup of women (p=n.s.), while
      younger men had higher ACTH responses compared to older men (p=0.01). For total
      plasma cortisol, ANOVA results showed that the pattern of reactivity did not
      differ between age and gender groups (all interactional effects p=n.s.), although
      older females had hightened overall cortisol levels compared to the other groups,
      as proofed in post hoc analyses (all p<0.05). For free salivary cortisol, a
      significant main effect of gender (p=0.05) and an almost significant three-way
      interaction (p=0.09) emerged. Post hoc analyses showed an elevated overall free
      salivary cortisol response in elderly men compared to elderly women (p=0.006),
      while no gender differences emerged in neither young adults nor children (both
      p=n.s.). In sum, the stressor induced significant HPA axis responses in all age
      and gender groups. The observed ACTH response patterns in young and elderly
      adults may suggest that a heightened hypothalamic drive in young men decreases
      with age, resulting in similar ACTH responses in elderly men and women.
      Alternative interpretations are also discussed. The data also supports the idea
      of a greater adrenal cortex sensitivity to ACTH signals in young females. Free
      salivary cortisol responses were elevated in elderly men compared to elderly
      women, an effect which cannot be explained by gender differences in perceived
      stress responses to the TSST. It can be speculated if corticosteroid binding
      globulin (CBG) and/or sex steroids are important modulators of these effects.

PMID- 14575732
TI  - High levels of cortisol among adolescent offspring of parents with bipolar
      disorder: a pilot study.
AB  - The hypothalamic-pituitary-adrenal (HPA) axis is compromised at several levels in
      major depressive and bipolar disorder (BD). However, it is not known whether HPA
      abnormalities predate the onset of these disorders. We conducted a pilot study
      comparing salivary cortisol levels of 10 adolescent offspring of parents with BD
      and 10 offspring of parents with no mental disorder (NMD). For two days, samples
      were collected at awakening and during the day in the adolescents' natural
      environment. The offspring of parents with BD had higher mean cortisol levels in
      the mornings and afternoons than the offspring of parents with NMD. When
      controlling for age, group differences in cortisol persisted in the afternoon,
      but not morning samples. None of the adolescents met diagnostic criteria for
      anxiety, affective, attention-deficit, or conduct disorders. Although
      preliminary, the results suggest that there is an early abnormality in the HPA
      system of the offspring of parents with BD.

PMID- 14575733
TI  - Intracerebroventricular administration of the angiotensin II receptor antagonist
      saralasin reduces respiratory rate and tidal volume variability in freely moving
      Wistar rats.
AB  - The possible importance of intra-individual variations in respiratory rate and
      tidal volume has recently gained interest in psychiatric research, as a result of
      the observations that patients with panic disorder or premenstrual dysphoric
      disorder display enhanced respiratory variability as compared to controls.
      Although the role of brain neurotransmitters in the regulation of breathing has
      been extensively studied, as yet data on the central regulation of respiratory
      variability is sparse. Prompted by previous studies indicating that angiotensin
      II (ANG II) may influence ventilation as well as anxiety, we have studied the
      effect of intracerebroventricular administration of an ANG II receptor
      antagonist, saralasin, on respiratory variability in unrestrained, freely moving
      male Wistar rats. Treatment with saralasin, 5 mug dissolved in 1 mul saline
      followed by 9 mul saline in each lateral cerebral ventricle, did not influence
      tidal volume, but markedly reduced tidal volume variability (p=0.0005), as
      compared to saline injections (10 mul). Respiratory rate was reduced by saralasin
      (p=0.02), and there was also a non-significant tendency for a reduction in
      respiratory rate variability. Both minute volume (p=0.005) and volume/10 s
      variability (p=0.0006) were reduced. It is suggested that ANG II in the brain of
      Wistar rats may regulate respiratory rate and tidal volume variability.

PMID- 14575734
TI  - The degradability of biodegradable plastics in aerobic and anaerobic waste
      landfill model reactors.
AB  - Degradabilities of four kinds of commercial biodegradable plastics (BPs),
      polyhydroxybutyrate and hydroxyvalerate (PHBV) plastic, polycaprolactone plastic
      (PCL), blend of starch and polyvinyl alcohol (SPVA) plastic and cellulose acetate
      (CA) plastic were investigated in waste landfill model reactors that were
      operated as anaerobically and aerobically. The application of forced aeration to
      the landfill reactor for supplying aerobic condition could potentially stimulate
      polymer-degrading microorganisms. However, the individual degradation behavior of
      BPs under the aerobic condition was completely different. PCL, a chemically
      synthesized BP, showed film breakage under the both conditions, which may have
      contributed to a reduction in the waste volume regardless of aerobic or anaerobic
      conditions. Effective degradation of PHBV plastic was observed in the aerobic
      condition, though insufficient degradation was observed in the anaerobic
      condition. But the aeration did not contribute much to accelerate the volume
      reduction of SPVA plastic and CA plastic. It could be said that the recalcitrant
      portions of the plastics such as polyvinyl alcohol in SPVA plastic and the highly
      substituted CA in CA plastic prevented the BP from degradation. These results
      indicated existence of the great variations in the degradability of BPs in
      aerobic and anaerobic waste landfills, and suggest that suitable technologies for
      managing the waste landfill must be combined with utilization of BPs in order to
      enhance the reduction of waste volume in landfill sites.

PMID- 14575735
TI  - Treatment of chemical mechanical polishing wastewater by electrocoagulation:
      system performances and sludge settling characteristics.
AB  - Treatment of copper chemical mechanical polishing (CMP) wastewater from a
      semiconductor plant by electrocoagulation is investigated. The CMP wastewater was
      characterized by high suspended solids (SS) content, high turbidity (NTU),
      chemical oxygen demand (COD) concentration up to 500 mgl(-1) and copper
      concentration up to 100 mgl(-1). In the present study, electrocoagulation was
      employed to treat the CMP wastewater with an attempt to simultaneously lower its
      turbidity, copper and COD concentrations. The test results indicated that
      electrocoagulation with Al/Fe electrode pair was very efficient and able to
      achieve 99% copper ion and 96.5% turbidity removal in less than 30 min. The COD
      removal obtained in the treatment was better than 85%, with an effluent COD below
      100 mgl(-1). The effluent wastewater was very clear and its quality exceeded the
      direct discharge standard. In addition, sludge settling velocities after
      electrocoagulation were measured and the data were employed to verify the
      empirical sludge settling velocity models. Finally, the sludge settling
      characteristic data were also utilized to establish the relation between the
      solids flux (G) and the initial solids concentration.

PMID- 14575736
TI  - Evaluation of dispersion methods for enumeration of microorganisms from peat and
      activated carbon biofilters treating volatile organic compounds.
AB  - To enumerate microorganisms having colonized biofilters treating volatile organic
      compounds, it is necessary firstly to evaluate dispersion methods. Crushing,
      shaking and sonication were then tested for the removal of microflora from
      biofilters packing materials (peat and activated carbon). Continuous or
      discontinuous procedures, and addition of glass beads had no effect on the number
      of microorganisms removed from peat particles. The duration of treatment also had
      no effect for shaking and crushing, but the number of microorganisms after 60 min
      of treatment with ultrasound was significantly higher than that obtained after
      0.5 min. The comparison between these methods showed that crushing was the most
      efficient for the removal of microorganisms from both peat and activated carbon.
      The comparison between three chemical dispersion agents showed that 1% Na
      pyrophosphate was less efficient, compared with 200 mM phosphate buffer or 1% Na
      hexametaphosphate. To optimize the cultivation of microorganisms, three different
      agar media were compared. Tryptic soy agar tenfold diluted (TSA 1/10) was the
      most suitable medium for the culture of microflora from a peat biofilter. For the
      activated carbon biofilter, there was no significant difference between Luria
      Bertoni, TSA 1/10, and plate count agar. The optimized extraction and enumeration
      protocols were used to perform a quantitative characterization of microbial
      populations in an operating laboratory activated carbon biofilter and in two
      parallel peat biofilters.

PMID- 14575737
TI  - Reduction of nitroaromatic pesticides with zero-valent iron.
AB  - Reduction of eleven nitroaromatic pesticides was studied with zero-valent iron
      powder. Average half-lives ranged from 2.8 to 6.3 h and the parent compounds were
      completely reduced after 48-96 h. The di-nitro groups of the 2,6-dinitroaniline
      herbicides were rapidly reduced to the corresponding diamines, with a negligible
      amount of partially reduced monoamino or nitroso products. Low levels of de
      alkylated products were observed after 10 days. The nitro group of the
      organophosphorus insecticides was reduced dominantly to the monoamines but in a
      slower rate than the 2,6-dinitroanilines. A trace amount of oxon products was
      found. Reduction of nitro to amino was also the predominant reaction for the
      diphenyl ether herbicides. Aromatic de-chlorination and de-alkylation were minor
      reactions. These amine products were more stable than the parent compounds and
      60% or more of the amines were detected after two weeks. Humic acid decreased the
      reduction rates of pendimethalin, and dichlone (a known quinone redox mediator)
      counteracted the effect of humic acid on the reactivity. Storage of iron powder
      under air decreased the reactivity very rapidly due to iron oxidation. Repeated
      use of iron powder also showed similar results. The reduced activity of air
      oxidized iron was recovered by purging with hydrogen, but not nitrogen.
      Integration of iron powder with hydrogen- and quinone-producing microbial
      technologies may be a viable mean for remediation of highly oxidized xenobiotics
      in the environment.

PMID- 14575738
TI  - Removal of DEHP in composting and aeration of sewage sludge.
AB  - The potential of composting and aeration to remove bis(2-ethylhexyl) phthalate
      (DEHP) from municipal sewage sludge was studied with two dewatered sludges: raw
      sludge and anaerobically digested sludge. Composting removed 58% of the DEHP
      content of the raw sludge and 34% of that of the anaerobically digested sludge
      during 85 days stabilisation in compost bins. A similar removal for the
      anaerobically digested sludge was achieved in a rotary drum in 28 days. Less than
      1% of DEHP was removed with the compost leachate. Although DEHP removal was
      greater from raw sludge compost than anaerobically digested sludge compost, the
      total and volatile solids removals were on the same level in the two composts. In
      the aeration of raw sludge at 20 degrees C the DEHP removals were 33-41% and 50
      62% in 7 and 28 days, respectively. Both composting and aeration are concluded to
      have the potential to reduce the DEHP contents typically found in sewage sludges
      to levels acceptable for agricultural use.

PMID- 14575739
TI  - Sorption equilibria of metal ions on bone char.
AB  - The ability of bone char to adsorb three metal ions, namely, copper(II), zinc(II)
      and cadmium(II) ions from wastewater has been studied. Three single-component
      equilibrium systems and three binary equilibrium systems have been measured
      experimentally. The three single-component equilibrium data were analyzed using
      the Langmuir and the Sips equilibrium isotherm equations. The Sips isotherm gave
      a better fit of the experimental data than the Langmuir isotherm based on the sum
      of squares errors (SSE) analysis. The Cu-Zn, Cu-Cd and Cd-Zn binary equilibrium
      experimental data were examined by incorporating the Langmuir and the Sips
      isotherm equations into the ideal adsorbed solution theory (IAST). The solution
      methods and the predicted results for the three binary systems at different metal
      ion compositions have been evaluated. In addition, the application of the IAST to
      the model prediction for the fixed bed system is presented.

PMID- 14575740
TI  - Bioleaching of heavy metals from livestock sludge by indigenous sulfur-oxidizing
      bacteria: effects of sludge solids concentration.
AB  - A technologically and economically feasible process called bioleaching was used
      for the removal of heavy metals from livestock sludge with indigenous sulfur
      oxidizing bacteria in this study. The effects of sludge solids concentration on
      the bioleaching process were examined in a batch bioreactor. Due to the buffering
      capacity of sludge solids, the rates of pH reduction, ORP rise and metal
      solubilization were reduced with the increase of the solids concentration. No
      apparent influence of solids concentration on sulfate produced by sulfur
      oxidizing bacteria was observed when the solids concentration was less than 4%
      (w/v). A Michaelis-Menten type of equation was able to well describe the
      relationship between solids concentration and rate of metal solubilization.
      Besides, high efficiencies of metal solubilization were achieved after 16 d of
      bioleaching. Therefore, the bioleaching process used in this study could be
      applied to remove heavy metals effectively from the livestock sludge.

PMID- 14575741
TI  - Decolorization of synthetic dyes using a copper complex with glucaric acid.
AB  - Selected azo, acridine, triphenyl methane, anthraquinone and thiazine-based dyes
      were decolorized using a catalytic system consisting of Cu(II)/glucaric
      acid/H(2)O(2). More than 90% decolorization was obtained with 100 ppm Acridine
      Orange, Azure B, Chicago Sky Blue, Crystal Violet, Methyl Orange, Poly B-411,
      Reactive Black 5, Reactive Blue 2, and Remazol Brilliant Blue R within 24 h.
      Seventy to eighty percent decolorization was achieved within the first 6 h. The
      decolorizaton was not affected by pH. The involvement of hydroxyl radicals
      produced in the system in the decolorization of the dye molecules was confirmed
      by electron spin resonance study.

PMID- 14575742
TI  - Cleaning oiled shores: laboratory experiments testing the potential use of
      vegetable oil biodiesels.
AB  - A series of laboratory experiments were carried out to test the potential of
      vegetable oil biodiesel for the cleaning of oiled shorelines. In batch
      experiments, biodiesel was shown to have a considerable capacity to dissolve
      crude oil, which appears to be dependent on the type of biodiesel used. Pure
      vegetable oil biodiesels (rapeseed and soybean) were significantly more effective
      in the cleanup of oiled sands (up to 96%) than recycled waste cooking oil
      biodiesel (70%). In microcosm and mesocosm experiments, oiled sediments were
      sprayed with biodiesel and subjected to simulated tides. Microcosm experiments
      revealed that, of those tested, the highest ratio of biodiesel to crude oil, had
      the highest effectiveness for cleaning fine sands, with ratios of 2:1
      (biodiesel:crude oil) giving the best results. In the mesocosm experiments a
      ratio 1:1 of soybean biodiesel to crude oil removed 80% of the oil in cobbles and
      fine sands, 50% in coarse sand and 30% in gravel. Most of the oil was removed
      with the surface water, with only a small amount being flushed through the
      sediments. Particle size and pore size were important determinants in the cleanup
      and mobility of crude oil in the sediments in these static systems. It is
      expected that the biodiesel effectiveness should improve in the natural
      environment particularly in exposed beaches with strong wave action. However,
      more laboratory and field trials are required to confirm the operational use of
      biodiesel as a shoreline cleaner.

PMID- 14575743
TI  - Trichloroethylene degradation by photocatalysis in annular flow and annulus
      fluidized bed photoreactors.
AB  - The effects of trichloroethylene (TCE) gas flow rate, relative humidity, TiO(2)
      film thickness, and UV light intensity on photodegradation of TCE have been
      determined in an annular flow type photoreactor. Phosgene and dichloroacetyl
      chloride formation could be controlled as a function of TCE gas flow rate and
      photodegradation of TCE decreased with increasing relative humidity. The optimum
      thickness of TiO(2) film was found to be approximately 5 mum and the
      photocatalytic reaction rate of TCE increased with square root of UV light
      intensity. In addition, the effects of the initial TCE concentration, phase
      holdup ratio of gas and solid phases (epsilon(g)/epsilon(s)), CuO loading on the
      photodegradation of TCE have been determined in an annulus fluidized bed
      photoreactor. The TCE photodegradation decreased with increasing the initial TCE
      concentration. The optimum conditions of the phase holdup ratio
      (epsilon(g)/epsilon(s)) and CuO wt.% for the maximum photodegradation of TCE was
      found to be 2.1 and 1.1 wt.%, respectively. Therefore, an annulus fluidized bed
      photoreactor is an effective tool for TCE degradation over TiO(2)/silica gel with
      efficient utilization of photon energy.

PMID- 14575744
TI  - The role of aqueous iron(II) and manganese(II) in sub-aqueous active barrier
      systems containing natural clinoptilolite.
AB  - Increasing attention is being placed on capping as a relatively new option in
      managing both contaminated sediments and dredged materials, due to its economic
      and environmental benefits. Capping denotes the placement of a cover onto
      potentially hazardous sediments or dredged material dumps to inhibit the transfer
      of contaminants into the water column. Retention of divalent iron and manganese
      cations using sandy capping layers containing natural zeolites as a reactive
      additive (active barrier systems, ABS) is evaluated in this study. Three
      different natural zeolite (clinoptilolite) rocks, two from deposits in Australia
      and one from a North-American deposit, were investigated and compared with
      respect to their mineralogical, physical and chemical properties. In particular,
      results from batch and column experiments show that ABS based on these materials
      can efficiently demobilise iron and manganese from percolating, anoxic pore water
      by cation exchange under favourable conditions. The retention, however, may be
      reduced strongly where competitive exchange with divalent cations such as calcium
      prevails or where mobile colloidal pore water constituents such as clay minerals
      or humic substances bind fractions of the dissolved iron or manganese. Therefore,
      the potential of ABS as a means for in situ remediation has to be evaluated
      diligently with particular regard to the pore water composition of the sediment
      to be capped.

PMID- 14575745
TI  - Removal of cyanide by woody plants.
AB  - Hydrogen cyanide is a high volume production chemical that causes severe
      environmental problems. The toxicity of potassium cyanide (KCN) to basket willow
      trees (Salix viminalis) was tested. In aqueous solution, 2 mg CN l(-1) as KCN
      depressed the transpiration after 72 h about 50%. Trees exposed to 0.4 mg CN l(
      1) in aqueous solution showed initially a depression of transpiration, but
      recovered. Doses of 8 and 20 mg CN l(-1) in aqueous solution were quickly mortal
      to the trees. At the end of the test, almost all cyanide had disappeared from the
      solutions. Levels of cyanide in plants were related to the toxicity, with no
      elevated levels of cyanide in plants exposed to 0.4 mg CN l(-1). Willows grown in
      sand survived 423.5 h irrigation with 20 mg CN l(-1). Willows grown in sand
      irrigated with 50 mg CN l(-1) died within a few days. The roots of the surviving
      willows were able to consume about 10 mg CN kg fresh weight(-1)h(-1). Vascular
      plants possess the enzymes beta-cyanoalanine synthase and beta-cyanoalanine
      hydrolase, which convert free cyanide to the amino acid asparagine. The in vivo
      capacity of woody plants (willow, poplar, elder, rose, birch) to remove cyanide
      was evaluated. Tests were performed with detached leaves and roots in KCN
      solutions of different concentrations. The highest removal capacity was obtained
      for basket willow hybrids (Salix viminalis x schwerinii). The Michaelis-Menten
      kinetics was determined. Realistic values of the half-saturation constant, K(M),
      were between 0.6 and 1.7 mg CN l(-1); the maximum metabolic capacity, v(max), was
      around 9.3 mg CN kg fresh weight(-1)h(-1). The removal of cyanide by plants might
      be useful in phytoremediation and treatment of wastewater from gold mining.

PMID- 14575746
TI  - Long-term characterization, lagoon treatment and migration potential of landfill
      leachate: a case study in an active Italian landfill.
AB  - The elaboration of 10 years of monitoring of leachate quality and quantity,
      leachate treatment and degree of contamination of soil and surface waters at the
      Tre Monti site--an active, 4-million-m(3) landfill in Northern Italy--is
      presented in this study. A hydrological model of leachate production is applied,
      with a good match of the experimental data. The concentrations of all leachate
      components except sulfate are characterized by fluctuations over a constant or
      increasing value. Different ways of interpreting leachate quality data are
      discussed; the elaboration indicates that the pollutant load on the leachate
      treatment facility will remain basically constant as long as waste will be added
      to the landfill. The analysis of the data relative to 10 years of leachate pre
      treatment in the adjoining, non-aerated lagoon system indicates that a
      significant removal is achieved for most leachate components; the operational
      conditions of the plant are described, and the removal mechanisms are discussed.
      Finally, the potential for contamination of soil and surface waters is examined
      by analyzing long-term quality trends of the sub-superficial waters sampled near
      the lagoons and by means of an analytical campaign conducted on clay cores
      sampled near and underneath the treatment ponds. The experimental values indicate
      that the clay layer located under the entire site offers an effective barrier to
      the migration of leachate contaminants.

PMID- 14575747
TI  - Ecological rehabilitation and phytoremediation with four grasses in oil shale
      mined land.
AB  - Vetiver grass (Vetiveria zizanioides), bahia grass (Paspalum notatum), St.
      Augustine grass (Stenotaphrum secundatum), and bana grass (Pennisetum glaucumxP.
      purpureum) were selected to rehabilitate the degraded ecosystem of an oil shale
      mined land of Maoming Petro-Chemical Company located in Southwest of Guangdong
      Province, China. Among them, vetiver had the highest survival rate, up to 99%,
      followed by bahia and St. Augustine, 96% and 91%, respectively, whereas bana had
      the lowest survival rate of 62%. The coverage and biomass of vetiver were also
      the highest after 6-month planting. Fertilizer application significantly
      increased biomass and tiller number of the four grasses, of which St. Augustine
      was promoted most, up to 70% for biomass, while vetiver was promoted least, only
      27% for biomass. Two heavy metals, lead (Pb) and cadmium (Cd) tested in this
      trial had different concentrations in the oil shale residue, and also had
      different contents and distributions in the four grass species. Concentrations of
      Pb and Cd in the four grasses presented a disparity of only 1.6-3.8 times, but
      their uptake amounts to the two metals were apart up to 27.5-35.5 times, which
      was chiefly due to the significantly different biomasses among them. Fertilizer
      application could abate the ability of the four species to accumulate heavy
      metals, namely concentration of heavy metals in plants decreased as fertilizer
      was applied. The total amount of metals accumulated by each plant under the
      condition of fertilization did not decrease due to an increase of biomass. In
      summary, vetiver may be the best species used for vegetation rehabilitation in
      oil shale disposal piles.

PMID- 14575748
TI  - Modelling of pharmaceutical residues in Australian sewage by quantities of use
      and fugacity calculations.
AB  - A conceptual model is presented for determining which currently prescribed
      pharmaceutical compounds are most likely to be found in sewage, and for
      estimating their concentrations, both in raw sewage and after successive stages
      of secondary sewage treatment. A ranking of the "top-50" pharmaceutical compounds
      (by total mass dispensed) in Australia over the 1998 calendar year was prepared.
      Information on the excretion ratios and some metabolites of the pharmaceuticals
      enabled prediction of the overall rates of excretion into Australian sewage. Mass
      balance and fugacity modelling, applied to sewage generation and to a sewage
      treatment plant, allowed calculation of predicted concentrations of the compounds
      in raw, primary and secondary treated sewage effluents. Twenty nine of the
      modelled pharmaceutical residuals were predicted to be present in raw sewage
      influent at concentrations of 1 microgl(-1) or greater. Twenty of the compounds
      were predicted to remain in secondary effluent at concentrations of 1 microgl(-1)
      or greater.

PMID- 14575749
TI  - Dry deposition of sulfate-containing particulate at the highway intersection,
      coastal and suburban areas.
AB  - Sulfate-containing aerosol (SCA) dry deposition at the highway intersection,
      coastal location, and suburban area in Taiwan were analyzed and compared.
      Sampling was accomplished with a surrogate surface technique. Samples particles
      were coated with barium chloride (BaCl(2)) in a vacuum evaporator and then
      exposed to a relative humidity of 85% for 2 h to form distinctive products of
      SCAs. Treated samples were examined by a scanning electron microscopy. SCA dry
      deposition fluxes were 10.2, 4.1, 3.4 microgm(-2)s(-1) and nonsulfate-containing
      aerosol (NSCA) dry deposition fluxes were 23.3, 8.2, 13.5 microgm(-2)s(-1) at the
      highway intersection, coastal, and suburban areas. At the highway intersection,
      both SCA and NSCA dry deposition fluxes were much higher than those at the other
      two sites. The dry deposition of particles was also analyzed with a traditional
      technique. The number median diameters (NMDs) of SCA were 0.41, 0.82, and 1.2 mum
      at the highway intersection, coastal, and suburban sites, respectively. The
      highway intersection site had a small NMD, which showed that most sulfate
      containing deposited aerosols existed in fine diameter range. The mass median
      diameters (MMDs) of SCA were 8.8, 19.5, and 14.9 mum at the highway intersection,
      coastal, and suburban sites, which were much higher than NMDs. Average numbers of
      SCAs in total particulate were 33%, 33%, and 22% at the highway intersection,
      coastal and suburban areas Most deposited particulates were nonsulfate-containing
      at the three sampling sites. SCAs less than 10 mum contributed 29%, 8%, and 7% to
      the total dry deposition at the highway intersection, coastal, and suburban
      areas, respectively. The contribution of fine particulate was significantly
      higher at the highway intersection site.

PMID- 14575750
TI  - Dynamics of carbon, nitrogen and hydrocarbons in diesel-contaminated soil amended
      with biosolids and maize.
AB  - Contamination of soil with hydrocarbons occurs frequently when petroleum ducts
      are damaged. Restoration of those contaminated soils might be achieved by
      applying readily available organic material. An uncontaminated clayey soil
      sampled in the vicinity of a duct carrying diesel which ruptured recently, was
      contaminated in the laboratory and amended with or without maize or biosolids
      while production of carbon dioxide (CO(2)), dynamics of ammonia (NH(4)(+)),
      nitrates (NO(3)(-)), and total petroleum hydrocarbons (TPH) were monitored. The
      fastest mineralization of diesel, as witnessed by production of CO(2), was found
      when biosolids were added, but the amount mineralized after 100 days,
      approximately 88%, was similar in all treatments. Approximately 5 mg of the 48 mg
      TPH kg(-1) found in the sterilized soil at the beginning of the experiment could
      not be accounted for after 100 days. The concentration of TPH in the unsterilized
      soil decreased rapidly in all treatments, but the rate of decrease was different
      between the treatments. The fastest decrease was found in the soil amended with
      biosolids and approximately 30 mg TPH kg(-1) or 60% could not be accounted for
      within 7 days. The decrease in concentration of TPH at the onset of the
      incubation was similar in the other treatments. After 100 days, the concentration
      of TPH was similar in all soils and appear to stabilize at 19 mg TPH kg(-1) soil.
      It was concluded that biosolids accelerated the decomposition of diesel and TPH
      due to its large nutrient content, but after 100 days the amount of diesel
      mineralized and the residual concentration of TPH was not affected by the
      treatment applied.

PMID- 14575751
TI  - Liquid chromatographic aqueous product characterization of high-energy electron
      beam irradiated 2-chlorobiphenyl solutions.
AB  - Polychlorinated biphenyls (PCBs) are of environmental concern due to their toxic
      nature. Ionizing radiation has been suggested as a means to remediate PCB
      contaminated samples in complex matrices. A set of experiments was performed to
      qualitatively and quantitatively determine the aromatic degradation products of 2
      monochlorobiphenyl (2-MCB) in an aqueous system exposed to ionizing radiation.
      The degradation of 2-MCB was observed in aqueous samples that were exposed to
      radiation from a linear accelerator electron beam source. Analytical measurements
      performed by liquid chromatography (LC) equipped with an ultraviolet (UV)
      detector revealed that biphenyl, o-hydroxybiphenyl, p-hydroxybiphenyl, phenol,
      chlorobenzene, and other unidentified products were created after 2-MCB
      irradiation. These results suggest that sensitive and selective analytical
      methods will be required to account for all degradation products during ionizing
      radiation of aqueous PCB-contaminated samples.

PMID- 14575752
TI  - Characterization of metal adsorption kinetic properties in batch and fixed-bed
      reactors.
AB  - Copper adsorption kinetic properties in batch and fixed-bed reactors were studied
      in this paper. The isothermal adsorption experiments showed that the copper
      adsorption capacity of a granular activated carbon (Filtrasorb 200) increased
      when ionic strength was higher. The presence of EDTA diminished the adsorption.
      An intraparticle diffusion model and a fixed-bed model were successfully used to
      describe the batch kinetic and fixed-bed operation behaviors. The kinetics became
      faster when the solution pH was not controlled, implying that the surface
      precipitation caused some metal uptake. The external mass transfer coefficient,
      the diffusivity and the dispersion coefficient were obtained from the modeling.
      It was found that both external mass transfer and dispersion coefficients
      increased when the flow rate was higher. Finally effects of kinetic parameters on
      simulation of fixed-bed operation were conducted.

PMID- 14575754
TI  - Recovery of astaxanthin from seafood wastewater utilizing fish scales waste.
AB  - The paper presents basic data on astaxanthin adsorption from fisheries wastewater
      to fish scales. This process has been proposed to be applicable in fisheries and
      shrimp waste management [Helgason, Recovery of compounds using a natural
      adsorbent, Patent WO 01/77230, 2001]. The innovative feature of the method is the
      application of a solid waste (fish scales) as a natural adsorbent for a
      carotenoid pigment (astaxanthin) from the seafood industry wastewater. The model
      investigations were performed with pure synthetic carotenoids to exclude the role
      of matrix in which astaxanthin is present in the wastewater. Under the
      experimental conditions used, the maximum loading capacity of astaxanthin onto
      the scales is 360 mg kg(-1) dry wt. Studies of the thus formed value added
      product indicated that drying causes significant loss of astaxanthin activity.
      Due to the effective filtration characteristics of the studied sorption material,
      we suggest the scale/astaxanthin sorption process to be suitable for treatment of
      wastewater from different industries.

PMID- 14575753
TI  - Photodegradation of surfactants on the nanosized TiO2 prepared by hydrolysis of
      the alkoxide titanium.
AB  - Nanosized TiO(2) was synthesized by hydrolysis of titanium tetraisopropoxide in
      the nanodroplets of microemulsions. The microemulsion provided by functionalized
      surfactants derived from the mixture of the commercially available sodium
      dodecylbenzensulfonate (DBS) and sodium dodecyl sulfate (DS). The resulting
      TiO(2) nanoparticles were characterized by transmission electron microscopy, X
      ray diffraction, and differential thermal analysis. Nanosized TiO(2) of anatase
      was found to show good photocatalytic properties in the photodegradation of DBS
      and DS surfactants. The cleavage of the aromatic moiety, the intermediate
      products and ultimate mineralization to CO(2) were examined in the process of
      photodegradation. A mechanism is also proposed on the basis of these experimental
      results.

PMID- 14575755
TI  - Surfactant-enhanced oxidation of trichloroethylene by permanganate--proof of
      concept.
AB  - Oxidative dechlorination of chlorinated solvents by permanganate is an emerging
      technology for remediation of groundwater contaminated with dissolved chlorinated
      contaminants. In this study, the enhancement of trichloroethylene (TCE)
      degradation by permanganate in aqueous solution in the presence of surfactant was
      evaluated through a continuous stir batch reactor system with the presence of
      permanganate as the limiting reagent and free phase TCE. The TCE degradation was
      determined by continuous monitoring the amount of chloride produced, which was
      then reverted to the rate of permanganate consumption. It was found that the
      chloride production, an indication of TCE degradation, followed a pseudo-first
      order reaction kinetics with respect to KMnO(4) in the presence of free phase
      TCE. When no surfactants were present, the observed pseudo-first-order rate
      constant (k(obs)) was 0.08-0.19 min(-1) and the half-life (t(1/2)) was 4-9 min
      for MnO(4)(-). When the surfactant concentration was less than its critical
      micelle concentration (CMC), the k(obs) values increased to 0.42-0.46 min(-1) and
      the t(1/2) reduced to 1.5-1.7 min for MnO(4)(-). As the surfactant concentration
      was greater than the CMC, the k(obs) values increased to 0.56-0.58 min(-1) and
      the t(1/2) reduced to 1.2-1.3 min. The preliminary results showed that
      combination of permanganate with a proper type of surfactant can speed up
      contaminant removal.

PMID- 14575756
TI  - Adsorption of water-soluble dyes onto modified resin.
AB  - Adsorption behavior of five kinds of water-soluble dyes onto functionalized resin
      NKY has been dynamically and thermodynamically investigated. The results showed
      that the adsorption rates of dye K-GN, K-2BP, KN-R, AAB and 2G are all controlled
      by liquid film diffusion and particle diffusion. Equilibrium adsorption data can
      be well described by three-parameter equation. The first layer adsorption is the
      physical enhanced by chemical effect but multilayer adsorption is typically
      physical adsorption. Standard free energy change DeltaG(0) and standard entropy
      change DeltaS(0) indicate the adsorption of the dyes onto NKY can occur
      spontaneously.

PMID- 14575757
TI  - Photocatalytic degradation of textile dye X3B by heteropolyoxometalate acids.
AB  - Reactive brilliant red X3B, one recalcitrant textile dye, was decolorized in
      water by (Photo)-Fenton reactions and TiO(2) photocatalysis [Chemosphere 43
      (2001) 1103]. Complementary to this study, the present work has shown the
      effectiveness of several Keggin-type heteropolyoxomatalates (POM) as a
      photocatalyst for X3B degradation in water at pH 1.0 under UV light (lambda>/=320
      nm) irradiation. Among four POMs, the relative activity was observed to be
      H(3)PW(12)O(40)z.Gt;H(4)SiW(12)O(40)>H(4)GeW(12)O(40)>H(3)PMo(12)O(40). The
      reaction was dependent of pH, light intensity and the catalyst loading, but not
      obviously of the molecular oxygen dissolved in water. Compared to the
      photocatalyst of TiO(2) (Degussa p25), H(3)PW(12)O(40) was less efficient for the
      dye bleaching and mineralization. The mechanism study reveals that hydroxyl
      radicals are involved in the degradation of X3B (and Rhodamine B) by POM
      photocatalysis.

PMID- 14575758
TI  - Color and COD removal from wastewater containing Reactive Black 5 using Fenton's
      oxidation process.
AB  - In this study, Reactive Black 5 (RB5) was removed from synthetic wastewater using
      Fenton's oxidation (FO) process. Experiments were conducted on the samples
      containing 100 and 200 mg l(-1) of RB5 to remove the dye toxicity. Seventy-five
      milligram per litre of RB5 caused 25% toxicity on 24-h born daphnids whereas 100
      mg l(-1) of RB5 displayed 100% toxicity on Daphnia magna. The study was performed
      in a systematic approach searching optimum values of FeSO(4) and H(2)O(2)
      concentrations, pH and temperature. Optimum pH and temperature for 100 mg l(-1)
      of RB5 were observed as 3.0 and 40 degrees C, respectively, using 100 mg l(-1) of
      FeSO(4) and 400 mg l(-1) of H(2)O(2) resulted in 71% chemical oxygen demand (COD)
      and 99% color removal. For 200 mg l(-1) of RB5, 84% COD removal was obtained
      using 225 mg l(-1) of FeSO(4) and 1000 mg l(-1) of H(2)O(2) yielding 0.05 molar
      ratio at pH 3.0 and 40 degrees C. Color removal was also more than 99%. The
      optimum conditions determined in accordance with the literature data. The
      H(2)O(2) requirement seems to be related to initial COD of the sample.
      FeSO(4)/H(2)O(2) ratios found were not changed for both concentrations. The
      temperature affected the COD removal significantly at high degrees. Toxicity was
      completely removed for each concentration of RB5 at optimum removal conditions.

PMID- 14575759
TI  - Hepatitis A vaccine failure: how to treat the threat.

PMID- 14575760
TI  - A prospective, Internet-based study of the effectiveness and safety of influenza
      vaccination in the 2001-2002 influenza season.
AB  - The effectiveness of the influenza vaccine used in the 2001-2002 influenza season
      in Japan was investigated in a large-scale, geographically widely distributed,
      Internet-based study. Data were collected from 8841 of 9902 subjects registered
      by 38 clinics prior to the start of influenza season. Subjects were categorized
      into three groups by vaccination regimen: unvaccinated, vaccinated once, and
      vaccinated twice. Efficacy was also analyzed for three age groups: 0-15, 16-64,
      and 65-104 years. Influenza-like illness (ILI) was diagnosed according to
      Ministry of Health (MWH, Labor and Welfare in Japan) criteria. Laboratory
      confirmed influenza cases were analyzed separately. The respective vaccine
      efficacy in the 0-15 years group for the one- and two-dose regimens was 67.6 and
      84.5% for ILI and 54.0 and 79.8% for laboratory-confirmed influenza. Influenza
      vaccination was also shown to be effective in subjects 16-64 years. Vaccine
      effectiveness was not able to be determined for the over 65 years group, probably
      due to an insufficient number of infected patients. These results suggest that
      influenza vaccination is effective for children and adults and that a two-dose
      regimen is superior to a single dose in children 0-15 years.

PMID- 14575761
TI  - Partial protective effect of inactivated Japanese encephalitis vaccine on lethal
      West Nile virus infection in mice.
AB  - The effect of mouse brain-derived, inactivated Japanese encephalitis (JE) vaccine
      on West Nile virus (WNV) infection was examined using a murine model. Mice were
      immunized with JE vaccine twice and challenged with lethal doses of WNV. When
      mice were intracranially challenged with WNV, none of the immunized mice were
      protected. When mice were intraperitoneally challenged, the immunized mice were
      protected at higher immunization levels. Cross-reactive neutralizing antibodies
      to WNV were induced by immunization with JE vaccine; however, the levels were
      much lower than those to JEV. These results indicate that the currently available
      mouse brain-derived inactivated JE vaccine can induce partial protective immunity
      to WNV in mice.

PMID- 14575762
TI  - Non-clinical and phase I clinical trials of a Vero cell-derived inactivated
      Japanese encephalitis vaccine.
AB  - The safety and effectiveness of a Vero cell-derived inactivated Japanese
      encephalitis (JE) vaccine were compared with those of a current JE vaccine in non
      clinical studies and a phase I clinical trial. The single-dose toxicity study
      showed no toxicity of either the current JE vaccine or the investigational Vero
      cell-derived JE vaccine. In a local irritation study, the degree of irritation
      caused by both vaccines was determined to be the same as that induced by normal
      saline. To investigate genotoxicity, a chromosomal aberration test was conducted
      and the results were negative. Both JE vaccines were administered to a group of
      30 subjects who were seronegative (neutralizing antibody titer <10(1)) for JEV
      virus (Beijing-1 Strain). Each subject was subcutaneously inoculated twice at an
      interval of 1-4 weeks, followed by an additional booster inoculation 4-8 weeks
      later, and clinical reactions and serological responses were subsequently
      investigated. Adverse drug reactions of local reaction, headache and malaise were
      mild, occurring at a rate of 6.7 and 20.0% after administration of the Vero cell
      derived JE vaccine and the current JE vaccine, respectively. The seroconversion
      rate after three doses of both JE vaccines was 100%, while the geometric mean
      titer for the Vero cell-derived and current JE vaccines was 10(2.35) and
      10(2.03), respectively. These results suggest that the safety and effectiveness
      of the Vero cell-derived inactivated JE vaccine are equal to those of the
      currently available conventional vaccine in humans, and that the Vero cell
      derived vaccine could be a useful second-generation JE vaccine.

PMID- 14575763
TI  - Mass psychogenic illness following oral cholera immunization in Ca Mau City,
      Vietnam.
AB  - INTRODUCTION: Targeted cholera immunization of high-risk populations in Vietnam
      is conducted based on routine surveillance data. Following mass immunization of
      schoolchildren in Ca Mau City using an oral bivalent killed cholera vaccine,
      adverse reactions were noted. METHODS: Salient data were collected in a
      systematic fashion including the review of medical records; interview of the
      school principal, teachers, students, parents and doctors; and review of the
      storage and handling of the vaccine. FINDINGS: On 18 December 2001, 234 children
      at a primary school in Ca Mau City received the cholera vaccine. Within 1h of
      immunization, three children in one of the classrooms complained of trembling,
      nausea and headache and were brought to the library and soon other children
      followed. Out of 234, 97 (42%) pupils were affected and brought to the Municipal
      Health Center or Ca Mau Provincial Hospital. Those who were affected were younger
      (mean age=9.6 years; 95% CI=9.4-9.7) compared to those who were not affected
      (mean age=10 years; 95% CI=9.7-10.3; t-test=-2.4; P-value=0.02). The proportion
      of affected females among those who had received the vaccine (49/114 or 43%) was
      similar to the proportion in males (48/120 or 40%; RR=1.07; 95% CI=0.79-1.46).
      The most frequent presenting complaint was cold extremities (60%) followed by
      headache (27%). All affected children recovered and were discharged in a few
      hours. None reported any sequelae or relapse. Once the situation was recognized,
      the cholera immunization campaign was continued. Laboratory tests of vaccine
      samples from the same batch detected no abnormality or contaminating agent.
      DISCUSSION: The findings suggest that the children at primary school number 1
      suffered from a mass psychogenic illness. This incident was unusual in that a
      similar number of boys and girls were affected, in contrast to the frequently
      reported preponderance of female cases. Furthermore the underlying cause was very
      quickly diagnosed, medical interventions were kept to a minimum, and no relapse
      was observed. Future vaccination campaigns have to assure that the families are
      informed in advance.

PMID- 14575764
TI  - Protection against influenza virus infection by intranasal administration of C3d
      fused hemagglutinin.
AB  - For the induction of mucosal immune responses by intranasal vaccination, cholera
      toxin B subunits (CTB) and Escherichia coli heat-labile toxin (LT) are often
      administered as mucosal adjuvants in order to enhance immune responses to
      mucosally co-administered bystander antigens. However, these toxin also are the
      causative agents of diarrhea. There is a demand for the establishment of an
      effective and safer adjuvant or vaccine that elicits mucosal immunity, but does
      not require the use of CTB or LT adjuvants. In order to induce protective mucosal
      immune responses in the nasal area against influenza virus infection, we have
      examined the recombinant protein composed of the complement component, C3d, which
      is fused to the secreted form of hemagglutinin (sHA-mC3d3) in the influenza
      BALB/c mouse model. The fusion protein sHA-mC3d3, the secretory form of
      hemagglutinin, and the transmembrane form of HA (tmHA) from the influenza virus
      were intranasally administered to the mice with or without CTB containing a trace
      amount of holotoxin (CTB*) as an adjuvant. After intranasal administration of
      these proteins with CTB*, all mice produced nasal IgA and serum IgG antibodies
      (Abs) against the viral HA. In addition, viral infection was completely inhibited
      in these mice. In contrast, in the absence of the adjuvant, only sHA-mC3d3
      induced locally secreted IgA and serum IgG Abs and provided complete protection
      against the influenza virus challenge. Thus, C3d fused to the influenza HA
      antigen is an effective and safe tool for mucosal vaccination.

PMID- 14575765
TI  - Bacterial otitis media: a new non-invasive rat model.
AB  - This study describes the development of a physiological rat model for otitis
      media. The model is based on the assumption that bacteria, intranasally
      introduced into the nasopharynx, will be transferred into the middle ear cavity
      during swallowing provided that the ambient air pressure is higher than the
      middle ear pressure. This model demonstrates that small pressure changes,
      generated in a pressure cabin under controlled conditions, can be used as driving
      force for the transfer of bacteria into the middle ear cavity resulting in
      bilateral otitis media. Because invasive techniques or biochemical agents are not
      applied, this model is suited to investigate immunological aspects of otitis
      media, including the effects of vaccination.

PMID- 14575766
TI  - Efficacy of granulocyte-macrophage colony-stimulating factor (GM-CSF) as a
      vaccine adjuvant for hepatitis B virus in patients with HIV infection.
AB  - Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) is
      a cytokine with a potential vaccine adjuvant activity. It is also known that
      human immunodeficiency virus (HIV) infected patients often show poor immunologic
      responses to immunization. We examined whether the use of GM-CSF could augment
      the immunologic response to recombinant vaccine against the hepatitis B virus
      (HBV) in 80 HIV infected patients (18-35 years old). They received a double dose
      (40 microg) of recombinant HBV vaccine IM at 0, 1 and 6 months and were
      randomized to receive either concurrent 20 microg of GM-CSF (n=40) or placebo IM
      (n=40) with the first vaccine dose. A significant increase in the seroconversion
      rate was observed after the second vaccine dose in the GM-CSF group (62% GM-CSF
      versus 30% control group P<0.0074). The average anti-HBs titers measured on days
      28, 60 and 210 were 40.3; 366.5 and 644.8 milli-international units per
      milliliter (mIU/ml), respectively, in the GM-CSF group, and 62.4; 166.4 and 375.0
      mIU/ml, respectively, in the control group, with significant differences at 60
      and 210 days (P<0.01). There were no significant differences between CD4/CD8
      cells, viral load, risk factors, age, sex and the serological responses to the
      HBV vaccine. This study suggests that GM-CSF increases the immunogenicity of
      recombinant HBV vaccine in HIV infected individuals.

PMID- 14575767
TI  - Development of a rapid method for determining the infectious dose (ID)50 of
      Orientia tsutsugamushi in a scrub typhus mouse model for the evaluation of
      vaccine candidates.
AB  - The infectious dose (ID) of an inoculum for which 50% of susceptible mice will
      become infected (ID(50)) with Orientia tsutsugamushi is usually determined by
      rechallenging mice that have already been challenged with O. tsutsugamushi to
      determine the lethal dose (LD)(50) titer of the inoculum. Those mice not killed
      by the initial challenge and which survived a rechallenge with 1000 LD(50) were
      considered immune and to have been initially infected with O. tsutsugamushi. Mice
      that succumbed to the rechallenge were considered not to have been initially
      infected. We have developed a more rapid method of determining the ID(50) of
      inocula for use in our vaccine studies based upon the observation that mice
      surviving initial challenge and that go on to survive rechallenge produced
      detectable IgG to O. tsutsugamushi antigens by enzyme-linked immunosorbent assay
      (ELISA). Mice that did not survive rechallenge, and therefore did not receive an
      initial infectious inoculum did not produce detectable IgG to O. tsutsugamushi
      antigens. Both original LD(50) and ID(50) titers determinations require
      observation of mice for 21 days post-challenge. Our new ID(50) determination does
      not require mice or the additional 21-day observation period for rechallenge and
      therefore is more rapid and cost-effective than the previous standard method of
      determining ID(50) titer necessary for the evaluation of vaccine candidates.

PMID- 14575768
TI  - Efficient induction of T helper 1 CD4+ T-cell responses to hepatitis C virus core
      and E2 by a DNA prime-adenovirus boost.
AB  - Hepatitis C virus (HCV) is an important causative agent of liver disease, but
      currently there is no available prophylactic vaccine against HCV infection. Here,
      we investigated the HCV E2- and core-specific T-cell responses induced by DNA (D)
      and/or recombinant adenovirus (A) vaccines. In single (D versus A) or double
      immunizations (D-D versus A-A), the recombinant adenovirus vaccines induced
      higher levels of IFN-gamma secreting T-cell response and cytotoxic T lymphocytes
      (CTL) response than the DNA vaccines. However, a heterologous (D-A) regimen
      elicited the highest level of T helper 1 (Th1) CD4(+) T-cell responses.
      Furthermore, three E2-specific CTL epitopes were mapped using a peptide pool
      spanning the E2 protein sequence (a.a. 384-713) in BALB/c mice, and one of these
      (E2 405-414: SGPSQKIQLV) was shown to be immunodominant. Interestingly, no
      significant differences were found in the repertoire of E2-specific T-cell
      responses or in the immunodominance hierarchy of the three epitopes induced by D
      D, D-A, A-A, and A-D, indicating that the breadth and hierarchy of T-cell
      responses is independent of these different vaccination regimens. In conclusion,
      the heterologous DNA prime-recombinant adenovirus boost regimen described offers
      an efficient promising strategy for the development of an effective T-cell-based
      HCV vaccine.

PMID- 14575769
TI  - Protection of swine against post-weaning multisystemic wasting syndrome (PMWS) by
      porcine circovirus type 2 (PCV2) proteins.
AB  - Porcine circovirus type 2 (PCV2) is known to be associated with post-weaning
      multisystemic wasting syndrome (PMWS), a recently described disease of young
      pigs. Since no PCV2 vaccine was available so far, we have developed a specific
      PCV2 vaccine candidate. The Orf1-encoded replication protein and Orf2-encoded
      capsid protein of PCV2 were expressed and detected in either mammalian or insect
      expression systems. In a first trial, Orf2 protein was found to be a major
      immunogen, inducing protection in a prime-boost protocol; the piglets received a
      first injection with plasmids directing Orf2 protein and granulocyte-macrophage
      colony-stimulating factor (GM-CSF) expression, followed by a second injection, a
      fortnight later, associated with baculovirus-expressed Orf2 protein. As evaluated
      by growth parameters, clinical signs (fever), seroconversion, the pigs were
      protected against a PCV2 challenge after vaccination. In a second trial,
      protection induced by a subunit vaccine was even better than the one induced by
      DNA vaccine, since PCV2 replication was completely inhibited.

PMID- 14575770
TI  - Phase I study of detoxified Escherichia coli J5 lipopolysaccharide (J5dLPS)/group
      B meningococcal outer membrane protein (OMP) complex vaccine in human subjects.
AB  - We previously observed that a detoxified Escherichia coli O111, Rc chemotype J5
      lipopolysaccharide (J5dLPS)/group B meningococcal outer membrane protein (OMP)
      vaccine protected animals from experimental lethal sepsis when immune antibodies
      were given passively as treatment at the onset of fever or when vaccine was given
      actively as prophylaxis. To test the safety and immunogenicity of this vaccine,
      we administered doses of 5, 10 and 25 microg (based on dLPS) of vaccine at days
      0, 28 and 56 to 24 human subjects (8 per group). Temperatures of 100.3, 99.5 and
      99.4 degrees F occurred in three subjects. At 24h, pain at the injection site was
      moderate in 38%, mild in 44% and not present in 18%, while at 48 h, it was 1, 25
      and 73%, respectively. No alterations in baseline renal, hepatic or hematologic
      functions occurred. There were two to three times mean-fold increases in anti
      J5dLPS IgG (range: 1.9-5.1) and IgM (range: 1.2-9.2) levels in subjects receiving
      the 10 and 25 microg doses. At 12-month follow-up, three of the original
      responders had continued elevation of antibody levels. A 25 microg booster dose
      of vaccine did not increase antibody levels among those responders and did not
      elicit antibodies among three subjects with no previous antibody response. The
      plasma from the six volunteers inhibited LPS-induced cytokine generation in human
      whole blood ex vivo. We conclude that this J5dLPS/OMP vaccine was safe and well
      tolerated with transient, local pain at the injection site. Vaccine formulations
      with different adjuvants are currently under investigation.

PMID- 14575771
TI  - Antibody titres after primary and booster vaccination of infants and young
      children with a virosomal hepatitis A vaccine (Epaxal).
AB  - To evaluate the immunogenicity and tolerability of Epaxal in infants and
      children, 30 infants (aged 6-7 months) and 30 children (aged 5-7 years) received
      a single intramuscular dose of the aluminium-free virosomal hepatitis A virus
      (HAV) vaccine Epaxal and a booster dose after 12 months. Anti-HAV antibody titres
      were measured at baseline (before injection), at 1 and 12 months after primary
      vaccination, and 1 month after the booster vaccination. Sixteen evaluable infants
      had maternal anti-HAV antibodies at baseline. Complete seroprotection (titre >/=
      20 mIU/ml) was achieved by all infants and children at Month 1 and at Month 12.
      Additionally, all subjects showed a strong antibody response to booster
      vaccination. In infants without maternal anti-HAV antibodies, the response was
      four-fold higher than in those with maternal anti-HAV antibodies. Both doses of
      Epaxal were well tolerated. These preliminary data suggest that Epaxal is an
      effective hepatitis A vaccine for children and infants from 6 months of age.

PMID- 14575772
TI  - Rabies DNA vaccine in the horse: strategies to improve serological responses.
AB  - In order for DNA vaccines to become a practical alternative to conventional
      vaccines their ability to induce antibody responses in large mammals needs to be
      improved. We used DNA vaccination against rabies in the horse as a model to test
      the potential of two different strategies to enhance antibody responses in a
      large mammalian species. The administration of the DNA vaccine in the presence of
      aluminum phosphate improved both the onset and the intensity of serological
      responses but was not potent enough to achieve seroconversion in all vaccinated
      ponies. However, when the DNA vaccine was formulated with the cationic lipid
      DMRIE-DOPE instead of aluminum phosphate, a very strong impact on both onset and
      intensity of serological responses was observed. This latter strategy ensured
      excellent seroconversion in all vaccinated ponies after a primary course of two
      injections, demonstrating a clear improvement of the homogeneity of the induced
      responses. These data indicate that rabies DNA vaccination is feasible in horses
      and further suggests that properly formulated DNA vaccines can generate immune
      responses in large veterinary species at a level comparable to the responses
      achieved with conventional vaccines.

PMID- 14575773
TI  - Modelling measles re-emergence as a result of waning of immunity in vaccinated
      populations.
AB  - An age-structured mathematical model of measles transmission in a vaccinated
      population is used to simulate the shift from a population whose immunity is
      derived from natural infection to a population whose immunity is vaccine-induced.
      The model incorporates waning of immunity in a population of vaccinees that
      eventually will become susceptible to a milder form of vaccine-modified measles
      with a lower transmission potential than unvaccinated classical measles. Using
      current estimates of duration of vaccine-derived protection, measles would not be
      expected to re-emerge quickly in countries with sustained high routine vaccine
      coverage. However, re-emergence is possible to occur several decades after
      introduction of high levels of vaccination. Time until re-emergence depends
      primarily on the contagiousness of vaccine-modified measles cases in comparison
      to classical measles. Interestingly, in a population with a high proportion of
      vaccinees, vaccine-modified measles and classical measles would occur essentially
      in the same age groups. Although waning of humoral immunity in vaccinees is
      widely observed, re-emergence of measles in highly vaccinated populations depends
      on parameters for which better estimates are needed.

PMID- 14575775
TI  - DNA vaccine encoding pertussis toxin S1 subunit induces protection against
      Bordetella pertussis in mice.
AB  - Pertussis toxin (PT) is the major virulence factor of Bordetella pertussis, and
      detoxified PT is a crucial antigen of acellular pertussis vaccine. Here, plasmid
      DNA expressing the pertussis toxin S1 subunit (pcDNA/S1) of B. pertussis was
      evaluated for immunogenicity and for the ability to induce protection against PT
      challenge or B. pertussis infection in mice. The gene gun delivery of pcDNA/S1,
      performed by inserting the S1 gene into a mammalian expression vector,
      successfully induced anti-PT IgG antibody production. Immunization of mice with
      pcDNA/S1 significantly inhibited leukocytosis-promoting activity caused by PT or
      B. pertussis. In addition, pcDNA/S1 induced significant protection against
      intracerebral challenge with a lethal dose of B. pertussis. The results of the
      present study demonstrated that a DNA vaccine encoding the PT-S1 subunit induced
      protection against B. pertussis infection in mice. Thus, this vaccine preparation
      is potentially applicable for the production of novel vaccines against B.
      pertussis infection.

PMID- 14575774
TI  - Hepatitis B DNA vaccine induces protective antibody responses in human non
      responders to conventional vaccination.
AB  - A novel DNA vaccine against hepatitis B virus was administered intraepidermally
      by particle-mediated epidermal delivery (PMED) to 16 human subjects who
      demonstrated absent or non-sustainable responses to conventional hepatitis B
      vaccination. Eleven subjects received three doses of vaccine at 56-day intervals,
      and five subjects received only a single vaccination. Each dose of vaccine
      contained 4 microg of plasmid DNA encoding the hepatitis B surface antigen
      (HBsAg). The vaccine was safe and well tolerated. Remarkably, the DNA vaccine
      elicited antibody responses in 12 of the 16 subjects after a licensed subunit
      vaccine failed to induce a lasting response after >/=3 vaccinations. This study
      provides evidence in humans for protective immunogenicity of a particle-mediated
      DNA vaccine in subjects who have responded suboptimally to conventional
      vaccination.

PMID- 14575776
TI  - Development of a vaccine for immunization against classical as well as variant
      strains of infectious bursal disease virus using reverse genetics.
AB  - Available IBDV vaccines based on classical IBDV strains do not induce full
      protection in the presence of maternally derived antibodies (MDA) against variant
      strains. The aim of this study was the generation of an IBDV chimera between both
      classical and variant strains. Characterization of the generated chimeric IBDV
      (D78-Chim) was performed in both cell culture and susceptible chickens using the
      classical vaccine strain D78 for comparison. Growth kinetics on cell culture
      showed that the D78-Chim replicates comparable to the live vaccine strain D78.
      Administration of the D78-Chim to SPF chickens resulted in equally high virus
      neutralizing antibodies titres against both, classical and variant IBDV strains.
      In vivo experiments in commercial chickens revealed that D78-Chim and D78 induced
      comparable bursal damage in presence of maternally derived antibodies. Both D78
      Chim and D78 viruses were able to breakthrough a similar level of MDA.

PMID- 14575777
TI  - Local force model for cardiac dynamics analysis from volumetric image sequences.
AB  - We propose a local force model based on the kinetics of the left ventricle (LV)
      surfaces to characterize the complex nonrigid motion that the heart undergoes.
      The left ventricle motion is analyzed in a coarse-to-fine fashion. First, global
      motion and deformation are analyzed and compensated with hierarchical surface
      modeling. Then, we propose a physics-based model of local deformation derived
      from the dynamics of independent point masses driven by local external force.
      Experimental results show that the ensembles of the estimated point mass
      trajectories match well with the realistic left ventricle surface dynamics.

PMID- 14575779
TI  - Hand bone segmentation in radioabsorptiometry images for computerised bone mass
      assessment.
AB  - From hand radiographs, the measurement of the bone density of hand bones is
      automatically performed, using units relative to an aluminium wedge, in order to
      know the absorption of the ray light intensity respect to a known substance. By
      means of a point distribution model, the variation modes of a statistical model
      of the phalanx are determined, and the boundaries of such bones localised, aiming
      to obtain their average grey level. The goal is to obtain an accurate and
      reliable computerised radiographic X-ray absorptiometry system for automatic bone
      mass assessment that can be easily applied to the population. The developed
      system has been tested and compared to other known methods with a high level of
      correlation.

PMID- 14575778
TI  - A method for the automatic characterization of bone architecture in 3D mice
      microtomographic images.
AB  - We developed an automatic method to characterize mice bone architecture from
      three-dimensional (3D) microtomographic images. The distal metaphyses of the
      femur of mice were imaged using 3D synchrotron radiation microtomography at the
      European Synchrotron Radiation Facility (ID19) with a voxel size of 6.65 mum.
      Within each reconstructed volume, a region of interest was defined and trabecular
      and cortical bones were automatically separated. Then, 3D morphologic and
      topologic model-independent parameters quantifying the 3D bone architecture were
      computed in both regions. The technique was applied to study the response of the
      C57BL/6J@Ico strain of mice submitted to a model of bone loss by hind limb
      unloading produced by tail-suspension.

PMID- 14575780
TI  - Automatic 3D vascular tree construction in CT angiography.
AB  - This study presents an automatic method for 3D reconstruction of vascular trees
      using computed-tomography angiographic (CTA) images. The program starts with the
      CTA slices, performs a sequential procedure of 3D image formation, preprocessing,
      segmentation, thinning, skeleton pruning and tree construction. It ends with
      vascular trees along with quantitative data about the trees such as values of
      diameter, length and bifurcation angles. All the involved algorithms are
      presented with the emphasis given to the skeleton pruning and tree construction
      algorithms. The skeletons obtained using a 3D thinning algorithm may contain
      cycles, spurs, isolated sticks, and non-unit-width parts, which hinder tree
      construction. As a solution to this problem, a skeleton pruning and tree
      construction algorithm is proposed. At each stage of the automatic procedure, 3D
      rendering is provided for visual inspection of the computed results. In the final
      output, the constructed vascular trees are visualized by rendering the 3D trees
      and the 3D binary image together in a transparent display mode. The program is
      carried out in a fully automatic fashion, with a few default settings.
      Occasionally, user intervention is needed at the 3D segmentation stage to impose
      an appropriate threshold when the automatic 3D segmentation is obviously sub
      optimal for vessel delineation. Experimental demonstrations on both coronary
      artery phantom and a cast of coronary artery tree of a swine animal model are
      provided.

PMID- 14575781
TI  - CT anatomy of pterygopalatine fossa and its communications: a pictorial review.
AB  - In this article, we present a pictorial review computed tomography (CT) anatomy
      of pterygopalatine fossa and its communications. Since it represents a major
      pathway for spread of inflammatory or neoplastic disease between the various
      compartments, being familiar with the high resolution CT appearance of
      pterygopalatine fossa and its communications is necessary in selected cases. The
      diagnostic difficulties in determining the intercompartmental spread is
      discussed.

PMID- 14575782
TI  - CT and MR findings of brain aspergillosis.
AB  - CT and MR findings of a case of brain aspergillosis with histopathologic
      correlation are reported. On both CT and MR images, there were multiple lesions
      in the corticomedullary junction (CMJ) that appeared to disrupt the cortical
      sulci and that were not enhanced by intravenous contrast material. In most of
      these lesions, there were centrally located structures that were enhanced by
      intravenous contrast material and that appeared to be continuous from markedly
      enhanced adjacent dilated cortical vessels. Histopathologic examination of the
      autopsy specimen showed multiple hemorrhagic infarcts in the CMJ with remaining
      dilated cortical vessels that had been thrombosed by aspergillus hyphae.

PMID- 14575783
TI  - Gadolinium-enhanced dynamic MRI of breast hemangioma.
AB  - We describe a patient with hemangioma of the breast. The tumor showed an Ill
      defined hypointense mass on T1-weighted imaging and hyperintense mass on T2
      weighted imaging. After bolus gadolinium injection, the tumor showed
      heterogeneous enhancement in early phase and in the time-intensity an early
      intensive enhancement was followed by a plateau. This intensive enhancement in
      the early phase is not limited to breast carcinoma but can be found in breast
      hemangiomas as well.

PMID- 14575784
TI  - Computer aided diagnosis for breast masses detection on a telemammography system.
AB  - A Computer-Aided Diagnosis (CAD) scheme for breast masses detection has been
      developed and integrated as a part of a telemammography system. This work derives
      from the close cooperation between the Laboratory for Radiologic Image Research
      of the University of Santiago de Compostela (Spain) and the company Intelsis
      Sistemas Inteligentes (Santiago de Compostela, Spain). This cooperation has been
      supported by funds from different projects, mainly from the European Union, the
      Spanish Health Administration, and the Galician Public Health's Service. As a
      result, a first prototype is ready to begin a demonstration project.

PMID- 14575785
TI  - Snake modeling and distance transform approach to vascular centerline extraction
      and quantification.
AB  - A new method for fully automated centerline extraction and quantification of
      microvascular structures in confocal microscopy (CM) images is presented. Our
      method uses the idea of active contour models as well as path planning and
      distance transforms for the three-dimensional centerline extraction of elongated
      objects such as vessels. The proposed approach is especially efficient for
      centerline extraction of complex branching structures. The method performance is
      validated in several CM images of both normal and stroked rat brains as well as
      simulated objects. The results confirm the efficiency of the proposed method in
      extracting the medial curve of vessels, which is essential for the computation of
      quantitative parameters.

PMID- 14575786
TI  - Inverse image alignment method for image mosaicing and video stabilization in
      fundus indocyanine green angiography under confocal scanning laser
      ophthalmoscope.
AB  - An efficient image registration algorithm, the Inverse Compositional image
      alignment method based on minimization of Sum of Squared Differences of images,
      is applied in fundus blood vessel angiography under confocal scanning laser
      ophthalmoscope, to build image mosaics which have larger field of view without
      loss of resolution to assist diagnosis. Furthermore, based on similar technique,
      the angiography video stabilization algorithm is implemented for fundus
      documenting. The actual underlying models of motion between images and
      corresponding convergence criteria are also discussed. The experiment results in
      fundus images demonstrate the effectiveness of the registration scheme.

PMID- 14575787
TI  - The Internet and medical collaboration using virtual reality.
AB  - Computed Tomography (CT) provides a large amount of data but the presentation of
      the data to a physician can be less than satisfactory. Ideally, the image data
      should be available to physicians in interactive 3D to allow for improved
      visualization, planning and diagnosis. A virtual reality representation that not
      only allows for the manipulation of the image but also allows for the user to, in
      effect, move inside the image remotely would be ideal. In this paper the research
      associated with virtual reality is discussed. A formalism is then presented to
      create, from the CT data, the virtual reality world in the Virtual Reality
      Modeling Language. An implementation is described of this formalism that uses the
      Internet to allow for users in remote locations to view and manipulate the
      virtual worlds.

PMID- 14575791
TI  - Pharmacological inhibition of outwardly rectifying Cl- currents in rat peritoneal
      mast cells: a comparison of different stilbene derivatives.
AB  - Diethylstilbestrol and other stilbene derivatives can provide some inhibition of
      the outwardly rectifying Cl- current (I(Cl-,OR)) in rat peritoneal mast cells. In
      order to elucidate structure-activity relationships of diethylstilbestrol, 12
      stilbenes as well as 17beta-estradiol and hexestrol were tested in rat peritoneal
      mast cells using the nystatin-perforated patch approach of the whole-cell patch
      clamp technique. Since trans-stilbene showed no effect, the substituents of
      diethylstilbestrol must be of importance. The introduction of only one hydroxy
      group in trans-stilbene produced potent inhibition of the I(Cl-,OR) (IC50: 3.3
      microM). But in contrast, resveratrol with hydroxy groups at positions 4, 3', and
      5' as well as methoxy substituted stilbene derivatives and 17beta-estradiol were
      ineffective. On the other hand, hexestrol potently inhibited I(Cl-,OR) indicating
      that the aromatic ring systems can also be connected by an ethyl bridge. In
      summary, a hydroxy group at position 4 (or 4') is a prerequisite for
      diethylstilbestrol-mediated inhibition of I(Cl-,OR).

PMID- 14575792
TI  - Inhibition by arachidonic acid and other fatty acids of dopamine uptake at the
      human dopamine transporter.
AB  - It is known that arachidonic acid, in addition to promoting release of dopamine,
      can inhibit its transport. The present study provides preliminary information on
      structure-activity relationships for uptake inhibition by rotating disk
      voltammetry in human embryonic kidney-293 cells expressing the human dopamine
      transporter. Except for anandamide, all other fatty acids studied at a
      pretreatment concentration of 80 microM caused significant reductions in Vmax but
      not Km. Increasing saturation of the hydrocarbon tails (partial saturation: oleic
      acid, linoleic acid; full saturation: arachidic acid, stearic acid, stearic acid
      ethyl ester) removed inhibitory activity incrementally, suggesting a role for cis
      unsaturation (folding/bending of hydrocarbon tails). The relative lack of effect
      of 5,8,11,14-eicosatetraynoic acid also supports the idea that less linear
      structures are less inhibitory on dopamine uptake. Esterification of the free
      carboxylic group (arachidonic acid ethyl ester) prevented most of the inhibitory
      activity, arguing against mere membrane lipid disruption. Finally, the endogenous
      cannabinoid anandamide greatly reduced uptake Vmax accompanied by a small
      decrease in Km, a potentially important effect on dopaminergic neurotransmission.

PMID- 14575793
TI  - Effects of acute and long-term diazepam administrations on neutrophil activity: a
      flow cytometric study.
AB  - This study analyzed the effects of acute and long-term diazepam treatments on rat
      peripheral blood neutrophil activity and cortisol serum levels. Rats were acutely
      and long-term (21 days, once daily) treated with diazepam (10 mg/kg) or its
      vehicle (1.0 ml/kg). Blood was collected 1 h after treatments for flow cytometric
      analysis of neutrophil oxidative burst and phagocytosis. Corticosterone and
      diazepam concentrations were also determined. Results showed that: (1) both
      diazepam treatments increased lipopolysaccharide (LPS) and phorbol myristate
      acetate (PMA)-induced neutrophil oxidative burst; (2) the increase in oxidative
      burst after Staphylococcus aureus induction in acutely treated animals was higher
      than that observed after long-term treatment; (3) phagocytosis is increased by
      acute diazepam treatment and decreased by a long-term regimen; (4) acute, but not
      long-term, diazepam treatment increased corticosterone levels; (5) diazepam
      plasmatic levels after acute and long-term treatments were not different. These
      results indicate the development of tolerance to diazepam effects on
      corticosterone serum levels but not on neutrophil activity.

PMID- 14575794
TI  - Effect of morphine, naloxone and histamine system on water intake in adult male
      rats.
AB  - The present study investigated the interaction between histamine and opioid
      systems on water intake in adult male rats. Intracerebroventricular (i.c.v.)
      injections were carried out in all experiments. Water intake was measured 1 h
      after drug injections. Administration of histamine (40-80 microg/rat) and
      naloxone (0.5-1 microg/rat) increased, while morphine (2.5 microg/rat),
      pyrilamine (25-50 microg/rat), the histamine H1 receptor antagonist, and
      ranitidine (10-20 microg/rat), the histamine H2 receptor antagonist, decreased
      water intake in isolated rats. Blockade of histamine H1 and H2 receptors
      attenuated the histamine-induced response. Pyrilamine, but not ranitidine,
      increased the inhibitory effect induced by morphine. Also, pharmacological
      blockade of histamine H1 and H2 receptors decreased the naloxone-induced effect
      on water intake. It is concluded that the histaminergic system may have a close
      interaction with morphine and naloxone on drinking behavior.

PMID- 14575795
TI  - GABA(B) receptor antagonist CGP-36742 enhances somatostatin release in the rat
      hippocampus in vivo and in vitro.
AB  - Here, we show the modulation of somatostatin functions in the hippocampus by the
      orally active 'cognition enhancer' GABA(B) receptor antagonist, (3-aminopropyl)n
      butylphosphinic acid (CGP-36742), both in vivo and in vitro. Using high-pressure
      liquid chromatography-coupled electrospray mass spectrometry, we measured a two
      fold increase in the extracellular level of somatostatin to CGP-36742 application
      in the hippocampus of anaesthetised rats. The basal release of [125I]somatostatin
      in the synaptosomal fraction was increased by CGP-36742 in concentrations lower
      than 1 muM. Simultaneous measurement of [14C]Glu and [3H]gamma-aminobutyric-acid
      ([3H]GABA) showed that CGP-36742 increased their basal release. However, prior
      [125I]somatostatin application suppressed the increase in the basal release of
      [14C]Glu and induced a net decrease in the basal release of [3H]GABA.
      Somatostatin application had a similar effect. In slices, CGP-36742 increased the
      postsynaptic effect of somatostatin on CA1 pyramidal cells. These results suggest
      a pre- and postsynaptic functional 'cross-talk' between coexisting GABA(B) and
      somatostatin receptors in the rat hippocampus.

PMID- 14575796
TI  - Differential effects of the 5-HT1A receptor agonist flesinoxan given locally or
      systemically on REM sleep in the rat.
AB  - The effects of flesinoxan, a selective 5-HT1A receptor agonist on spontaneous
      sleep, were studied in adult rats implanted for chronic sleep recordings.
      Flesinoxan was administered systemically or infused directly into the dorsal
      raphe nucleus, the left laterodorsal tegmental nucleus or the medial pontine
      reticular formation. Systemic administration of flesinoxan (0.03 and/or 0.06
      micromol/kg) significantly increased wakefulness and sleep latencies, and reduced
      rapid eye movement (REM) sleep and the number of REM periods, during the first
      and/or second 2-h period after treatment. Direct infusion of the 5-HT1A receptor
      agonist (0.06 and/or 0.12 nmol) into the dorsal raphe nucleus induced a
      significant increment of REM sleep and augmented the number of REM periods during
      the second and/or third 2-h period of recording. Microinjection of flesinoxan
      (0.03, 0.06 and/or 0.12 nmol) into the laterodorsal tegmental nucleus reduced REM
      sleep and the number of REM periods, and augmented REM sleep latency during the
      first, second and/or third 2-h recording period. Finally, direct infusion of
      flesinoxan (0.48 nmol) into the medial pontine reticular formation decreased REM
      sleep and the number of REM periods, and increased REM sleep latency during the
      first and second 2 h of recording. Our results indicate that the 5-HT1A receptor
      is involved in the inhibitory effect of serotonin on brainstem structures that
      act to promote and to induce REM sleep.

PMID- 14575797
TI  - The very-high-efficacy 5-HT1A receptor agonist, F 13640, preempts the development
      of allodynia-like behaviors in rats with spinal cord injury.
AB  - Central neuropathic pain after spinal cord injury (SCI) presents a challenging
      clinical problem with limited treatment options. [(3-chloro-4-fluoro-phenyl)-[4
      fluoro-4-([(5-methyl-pyridin-2-ylmethyl)-amino]-methyl)piperidin-1-yl]]-methadone
      (F 13640) is a recently discovered very-high-efficacy, selective 5-HT1A receptor
      agonist that produces a remarkably powerful, central analgesia through
      unprecedented neuroadaptive mechanisms. In a rat model of spinal cord injury
      pain, we previously found that chronic infusion of F 13640 alleviated pain-like
      behaviors. Here, we report that infusion of 0.63 mg/day of F 13640 for 8 weeks
      starting 24 h before the induction of injury significantly attenuates the
      development of chronic allodynia-like behavior in rats sustaining a
      photochemically-induced, ischaemic injury of the dorsal laminae of the L3-L5
      segments of the spinal cord. Importantly, the preemptive effect of F 13640
      persisted for 2 months after treatment was discontinued. The data warrant the
      study of the possible effects of the early administration of F 13640 in patients
      sustaining spinal cord injury.

PMID- 14575798
TI  - Modulation by alpha-difluoromethyl-ornithine and aminoguanidine of pain
      threshold, morphine analgesia and tolerance.
AB  - The effects of alpha-difluoromethyl-ornithine (DFMO) and aminoguanidine, which
      might influence the metabolism of endogenous agmatine, on pain threshold,
      morphine analgesia and tolerance were investigated in mice. In the mouse acetic
      acid writhing test, intracerebroventricular (i.c.v.) injection of DFMO or
      aminoguanidine significantly elevated the pain threshold as indicated by a
      decrease in the number of writhings. DFMO or aminoguanidine obviously increased
      the analgesic effect of morphine in the mouse acetic acid writhing test and the
      mouse heat radiation tail-flick assay. These effects of DFMO and aminoguanidine
      were antagonized by idazoxan (3 mg/kg, i.p.), which is a selective antagonist of
      the imidazoline receptor. In the mouse heat radiation tail-flick assay,
      aminoguanidine significantly prolonged the tail-flick latency of animals,
      suggesting that the pain threshold was elevated. Furthermore, both DFMO and
      aminoguanidine enhanced morphine analgesia and inhibited acute morphine tolerance
      in the mouse heat radiation tail-flick assay. Neither DFMO nor aminoguanidine
      inhibited the activity of nitric oxide synthase in different brain areas in mice
      in vivo. These results indicate that the substances involved in the metabolism of
      endogenous agmatine could modulate the pain threshold, morphine analgesia and
      tolerance, indicating the possible role of endogenous agmatine in the
      pharmacological effects of morphine.

PMID- 14575799
TI  - Anti-allodynic and anti-oedematogenic properties of the extract and lignans from
      Phyllanthus amarus in models of persistent inflammatory and neuropathic pain.
AB  - This study investigated the anti-allodynic and anti-oedematogenic effects of the
      hexanic extract, lignan-rich fraction and purified lignans from a plant used in
      the traditional medicine, Phyllanthus amarus, in the inflammatory and neuropathic
      models of nociception. The hexanic extract inhibited the allodynia and the oedema
      induced by the intraplantar injection of complete Freund's adjuvant (CFA). The
      inhibition observed was 76 +/- 7% (ipsilateral paw), 64 +/- 7% (contralateral
      paw), and 41 +/- 2% (oedema). Otherwise, the lignan-rich fraction or the pure
      lignans did not affect CFA-induced allodynia. Administered chronically, the
      lignan fraction reduced CFA-induced paw oedema (39 +/- 9%). When evaluated in the
      model of neuropathic pain caused by partial ligation of sciatic nerve, the
      hexanic extract inhibited the mechanical allodynia (77 +/- 7%), with a similar
      efficacy to the gabapentin (71 +/- 10%). The anti-allodynic effects of hexanic
      extract of P. amarus seem not to be associated with the impairment of motor co
      ordination or with the development of tolerance. Finally, the treatment with
      hexanic extract inhibited the increase of myeloperoxidase activity, either
      following intraplantar injection of CFA or after sciatic nerve injury. It is
      concluded that, apart from its anti-inflammatory actions, which are probably
      linked to the presence of lignans, another as yet unidentified active
      principle(s) present in the hexanic extract of P. amarus produces pronounced anti
      allodynia in two models of inflammatory and neuropathic pain. Considering that
      few drugs are currently available for the treatment of chronic pain, especially
      of the neuropathic type, the present results may have clinical relevance and open
      new possibilities for the development of new anti-allodynic drugs.

PMID- 14575800
TI  - The antinociceptive effect of amisulpride in mice is mediated through opioid
      mechanisms.
AB  - Antinociceptive effects of various neuroleptics in animal acute pain-models have
      been described, mediated trough different pathways including the opioid system.
      In this study, we assessed the antinociceptive effects of the atypical
      neuroleptic drug amisulpride, which acts as a selective blocker of dopamine D2
      and D3 receptors. Furthermore, at low doses amisulpride has a selective
      preference for presynaptic dopamine autoreceptors, while at high doses it
      manifests a preferential action at post-synaptic dopamine receptors. We found
      amisulpride to be a potent antinociceptor agent in the mouse tail-flick assay,
      with an ED50 of 36.6 mg/kg. This effect was antagonized by naloxone (P<0.05),
      indicating an involvement of opioid mechanisms as mediators of the
      antinociceptive effect of amisulpride. Beta-funaltrexamine (mu1- and mu2-opioid
      receptor antagonist), naloxonazine (selective mu1-opioid receptor antagonist),
      naltrindole (selective delta-opioid receptor antagonist), Nor-binaltorphamine
      (kappa1-opioid receptor antagonist) reversed amisulpride antinociception at the
      same dose that they antagonized morphine's antinociceptive effect (all P<0.005).
      We found that the sensitivity of amisulpride-induced antinociception is mediated
      through selective involvement of all three opioid receptor subtypes. Based on
      previous studies with risperidone, clozapine and olanzapine we tend to attribute
      this global interaction with the opioid system to amisulpride's action at the
      dopamine D2 receptor sites.

PMID- 14575801
TI  - Use-dependent blockade of cardiac pacemaker current (If) by cilobradine and
      zatebradine.
AB  - The action of the bradycardiac agents, cilobradine (DK-AH269) and zatebradine (UL
      FS49), on the cardiac pacemaker current (If) was investigated on short Purkinje
      fibres from sheep hearts, using the two-microelectrode voltage-clamp technique,
      and on isolated rabbit sino-atrial cells with the patch clamp technique. These
      drugs reduce dose dependently the amplitude of the If, without modifying either
      the voltage dependence or the kinetics of channel activation. When voltage-clamp
      pulse trains were applied, cilobradine induced a use-dependent blockade of If
      that was stronger and faster than that with zatebradine. Recovery from blockade
      during prolonged hyperpolarization was significantly faster with zatebradine.
      Presumably, both drugs block the hyperpolarization-activated cyclic nucleotide
      gated (HCN) channel by gaining access to a binding site within the open channel
      pore, and are removed from the blocking site by strong hyperpolarization with
      large inward If through the open channel. Cilobradine, compared to zatebradine
      blocks If more effectively and faster in both preparations. Consequently
      cilobradine strongly reduces the pacemaker diastolic depolarization rate and the
      cell's firing frequency.

PMID- 14575802
TI  - Involvement of calcitonin gene-related peptide and capsaicin-sensitive afferents
      in central thyrotropin-releasing hormone-induced hepatic cytoprotection.
AB  - The involvement of capsaicin-sensitive afferent neurons and calcitonin gene
      related peptide (CGRP) in central thyrotropin-releasing hormone (TRH)-induced
      hepatic cytoprotection was investigated in rats. Both systemic capsaicin
      pretreatment and intravenous administration of CGRP receptor antagonist, human
      CGRP-(8-37), completely abolished the protective effect of intracisternal TRH
      analog (RX-77368; p-Glu-His-(3,3'-dimethyl)-Pro-NH2, 5 ng) against carbon
      tetrachloride (CCl4)-induced acute liver injury, assessed by serum alanin
      aminotransferase levels and histological changes. These data demonstrate the
      involvement of capsaicin-sensitive afferent neurons and CGRP in central TRH
      induced hepatic cytoprotection.

PMID- 14575803
TI  - Involvement of mast cell chymase in bleomycin-induced pulmonary fibrosis in mice.
AB  - The possible role of mast cell chymase in organ fibrosis was examined using a
      bleomycin-induced pulmonary fibrosis model in mice. Intratracheal injection of
      bleomycin to mice significantly increased not only hydroxyproline content but
      also chymase activity in the lung. Administration of a chymase inhibitor SUN
      C8077 (7-chloro-3-(3-amynophenyl) quinazoline-2, 4-dione methanesulfonate) dose
      dependently reversed the bleomycin-induced increase in hydroxyproline content as
      well as chymase activity in the lung. Human chymase digested latent transforming
      growth factor-beta1 (TGF-beta1) to form mature TGF-beta1 in vitro, which was
      inhibited by SUN C8077. Human chymase, on the other hand, failed to stimulate DNA
      synthesis of human lung fibroblasts CCD-8Lu and LL97A. Taken together, it is
      suggested that mast cell chymase might participate in the pathogenesis of
      pulmonary fibrosis, and that the chymase-induced fibrosis might be mediated at
      least in part by TGF-beta1. Chymase inhibitor may be promising for treatment of
      pulmonary fibrosis in humans.

PMID- 14575804
TI  - A novel and selective Na+/Ca2+ exchange inhibitor, SEA0400, improves
      ischemia/reperfusion-induced renal injury.
AB  - We evaluated the effects of SEA0400 (2-[4-[(2,5-difluorophenyl)methoxy]phenoxy]-5
      ethoxyaniline), a novel and selective Na+/Ca2+ exchange inhibitor, on ischemic
      acute renal failure. Ischemic acute renal failure in rats was induced by clamping
      the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after
      the contralateral nephrectomy. SEA0400 administration (0.3, 1 and 3 mg/kg, i.v.)
      before ischemia dose-dependently attenuated the ischemia/reperfusion-induced
      renal dysfunction and histological damage such as tubular necrosis. SEA0400
      pretreatment at the higher dose suppressed the increment of renal endothelin-1
      content after reperfusion. The ischemia/reperfusion-induced renal dysfunction was
      also overcome by post-ischemia treatment with SEA0400 at 3 mg/kg, i.v. In in
      vitro study, SEA0400 (0.2 and 1 microM) protected cultured porcine tubular cells
      (LLC-PK1) from hypoxia/reoxygenation-induced cell injury. These findings support
      the view that Ca2+ overload via the reverse mode of Na+/Ca2+ exchange, followed
      by endothelin-1 overproduction, plays an important role in the pathogenesis of
      ischemia/reperfusion-induced renal injury. The possibility exists that a
      selective Na+/Ca2+ exchange inhibitor such as SEA0400 is useful as effective
      therapeutic agent against ischemic acute renal failure in humans.

PMID- 14575805
TI  - The cytoprotective role of a low-molecular-weight heparin fragment studied in an
      experimental model of glomerulotoxicity.
AB  - Abnormal glomerular glycosaminoglycan metabolism is involved in the onset of the
      morphological and functional aberrations of glomerulopathies. In the present
      study, a heparin derivative, low-molecular-weight heparin, was tested for its
      ability to afford renoprotection in an established model of experimental
      glomerulopathy. Two groups of male albino rats of the Wistar strain (140 +/- 10
      g) received a single intravenous injection of adriamycin (7.5 mg/kg) to induce
      glomerulopathy, and one of them received low-molecular-weight heparin (Certoparin
      Sodium, Troparin; 300 microg/day/rat s.c.) treatment, commencing on day 8, for a
      week. Urinary protein/creatinine ratio, serum albumin, urea, uric acid and
      creatinine clearance were evaluated. Renal cell injury was assessed in terms of
      renal tissue lactate dehydrogenase, aminotransferases (aspartate and alanine
      transaminases) and alkaline phosphatase activities, as well as renal antioxidant
      status (superoxide dismutase, catalase and glutathione peroxidase, reduced
      glutathione, vitamins E and C). The kidney tissue was subjected to
      histopathologic examination. Low-molecular-weight heparin significantly reduced
      proteinuria and improved creatinine clearance and serum albumin levels in the
      rats with glomerulopathy. The significant rise in serum uric acid in the rats
      with glomerulopathy was reversed by low-molecular-weight heparin. Altered tissue
      enzyme activities in response to injury, oxidative stress challenged renal
      antioxidant system and abnormal renal histology were observed in the untreated
      nephrotic rats, while low-molecular-weight heparin treatment protected the
      nephrotic rats against these changes. Thus, in this study, low-molecular-weight
      heparin was evaluated for its role in combating glomerular injury, on the basis
      of some salient biochemical parameters, oxidative injury indices and histologic
      picture. The ability of low-molecular-weight heparin to restore glomerular
      anatamo-functional features in this nephrotoxic condition illuminates its multi
      faceted renoprotective role.

PMID- 14575806
TI  - Effect of opioid receptor ligands on the mu-S196A knock-in and mu knockout mouse
      vas deferens.
AB  - We have determined the effect of naltrexone, naloxone, [D-Ala2,D-Leu5]enkephalin
      (DADLE), and morphine on the mu-S196A opioid receptor knock-in and mu-opioid
      receptor knockout mouse vas deferens preparations. The antagonists, naltrexone
      and naloxone, exhibited agonist activity and possessed IC50 values that were 14-
      and 37-fold greater than morphine on the S196A preparation. Morphine was found to
      be threefold more potent at S196A relative to wild-type mu-opioid receptor. The
      mouse vas deferens data suggest that S196 in transmembrane helix 4 of the mu
      opioid receptor modulates efficacy. It is proposed that this may be due to
      decreased dimerization of the receptor. Identical IC50 values of DADLE obtained
      on the wild-type, S196A knock-in, and mu-opioid receptor knockout preparations
      support the absence of mu-delta heterodimers in the mouse vas deferens.

PMID- 14575807
TI  - Probucol restores the defective leukocyte-endothelial interaction in experimental
      diabetes.
AB  - Defective leukocyte-endothelial interactions have been observed in experimental
      type 1 diabetes. One of the mechanisms involved in the late complications of
      diabetes mellitus is the formation of free radicals species. Antioxidant
      treatment has been demonstrated to have beneficial effects on the complications
      observed in this pathology. Using intravital microscopy to visualize venules of
      the internal spermatic fascia, we demonstrated that the defective leukocyte
      endothelial interactions in alloxan-induced diabetic rats could be corrected by
      probucol treatment. The defects were quantitated by the number of leukocytes
      rolling along the venular endothelium, sticking to the venular wall after topical
      application of zymosan-activated plasma (10%-0.1 ml) or leukotriene B4 (1
      microM/0.1 ml) and migrated after the application of a local irritant stimulus
      (carrageenan, 100 microg/0.1 ml). Leukocyte counts, erythrocyte velocity and
      venular shear rate, unaltered in diabetic rats, were not modified by this
      treatment. Reactive oxygen species formation by endothelial cells increased in
      diabetic preparations, and the reduced expression of adhesion molecules such as
      intercellular adhesion molecule-1 (ICAM-1) and P-selectin in cross-sections of
      the whole testis of the animals, were both restored by the antioxidant agent.
      Therefore, antioxidant treatment improves leukocyte-endothelial interaction in
      diabetic rats at least in part by restoring the expression of adhesion molecules
      in venules of diabetic rats.

PMID- 14575808
TI  - Atypical behavioural responses to CCK-B receptor ligands in Fawn-Hooded rats.
AB  - At present there is an increasing literature demonstrating heterogeneity of the
      CCK-B receptor. Recent reports by our laboratory have demonstrated that the Fawn
      Hooded rat demonstrates atypical neurochemical responses to CCK4, in vitro. Since
      the ability of CCK-B receptor ligands to modulate affective state is dependent on
      the putative receptor subtype activated, the aim of the present study was to
      examine the behavioural effects of the CCK-B receptor agonist, t-boc-CCK4, and
      the CCK-B receptor antagonist, Ci-988 in Fawn-Hooded and Wistar Kyoto rats.
      Interestingly, both t-boc-CCK4 and Ci-988 produced an anxiolytic profile in FH
      rats as determined by an increased time spent on the open arms of an elevated
      plus maze, while both drugs were devoid of any behavioural effect in WKY rats,
      lending further support to the theory that the FH rat strain has an atypical
      relative proportion of these putative subtypes apparently resulting in a
      predominantly CCK-B2 receptor effect.

PMID- 14575809
TI  - Non-functional Fas ligand increases the formation of cartilage early in the
      endochondral bone induction by rhBMP-2.
AB  - It has previously been shown that mice with a defect in Fas ligand-mediated
      apoptosis have an enhancement of ectopic bone formation. We investigated the
      expression of bone-related markers--alkaline phosphatase, collagen, bone
      sialoprotein, osteocalcin, osteopontin, and bone morphogenetic proteins (BMP) -2,
      -4, and -7; and cytokines interleukin-1alpha (IL-1), IL-1beta, and tumor necrosis
      factor-alpha (TNF-alpha) in ectopic new bone induced by recombinant human (rh)
      BMP-2 in mice without functional Fas-ligand (gld mice). At day 6 after rhBMP-2
      implantation, gld mice formed more cartilage and mesenchyme compared with their
      wild type littermates. At later stages, gld mice did not differ from the control
      mice in the volume of newly formed tissue, expressing higher level of BMP genes
      and lower levels of genes involved in osteoblast maturation--bone sialoprotein
      and osteopontin. Differences in the levels of expression of IL-1alpha and TNF
      alpha were observed only at day 12 after rhBMP-2 implantation. These results
      suggest that gld mice have an increased recruitment of cells of mesenchymal
      origin and an abnormal pattern of differentiation and maturation of the newly
      formed mesenchymal tissues.

PMID- 14575810
TI  - A novel methylthio metabolite of s-triazolo[3,4-a]phthalazine, a lead compound
      for the development of antianxiety drugs, in rats.
AB  - When s-triazolo[3,4-a]phthalazine (Tri-P) was orally administered in rats, a more
      lipophilic metabolite M-1 than the parent compound was isolated from the urine.
      The metabolite M-1 was identified as 7-methylthio Tri-P by means of high
      resolution MS and two-dimensional NMR spectrometry. Furthermore, the 7-methylthio
      conjugate was generated from the parent compound Tri-P in isolated rat
      hepatocytes. Although the contribution of the intestinal microflora to the
      formation of methylthio metabolite has been pointed out so far, the limited data
      in this study lead us to conclude that the liver plays a role in all metabolic
      reactions of Tri-P to its 7-methylthio conjugate in rats.

PMID- 14575811
TI  - Delayed activation and regulation of MKK7 in hippocampal CA1 region following
      global cerebral ischemia in rats.
AB  - c-Jun N-terminal protein kinase (JNK) activation and subsequent c-Jun
      phosphorylation which stimulates its transcriptional activity have been well
      studied in cerebral ischemia. To determine whether mitogen-activated protein
      kinase kinase 7 (MKK7) play a role in JNK activation in response to the stress of
      global cerebral ischemia, we tested the activation of such a kinase by using
      phospho-Ser and phospho-Thr antibodies. Immunoprecipitation and Western blot
      analysis revealed that MKK7 was expressed at similar levels in all conditions,
      whereas phospho-MKK7 was highly augmented from 1 to 5 days and reached its peak
      at 3 days after 15 min of ischemia. Consistent with the active phase, the
      interaction of MLK3, ASK1 and phospho-JNK with MKK7 was increased compared with
      sham control, as shown by coimmunoprecipitation experiments. Moreover, MKK7
      activation was markedly reduced by pretreatment of the free radical scavenging
      thiol antioxidant N-acetylcysteine (NAC). Together with previous studies, the
      late activation of MKK7 in hippocampal CA1 region may contribute to delayed cell
      death, and the protective effects of antioxidant against ischemia-induced injury
      may be partially mediated by the down-regulation of JNK signal pathway.

PMID- 14575812
TI  - Narghile (water pipe) smoking influences platelet function and (iso-)eicosanoids.
AB  - The biological effects of smoking water pipe on haemostasis and the eicosanoid
      system is unknown. Water pipe smoking is familiar to approximately 1 billion
      people around the world. Considering this quite impressive number, we
      investigated the potential effect of smoking the Narghile on oxidation injury by
      monitoring parameters of the (iso)eicosanoid system. Patients were allowed to
      smoke a water pipe once daily for 14 days. Blood was drawn from 7 healthy adult
      non-cigarette smoking male volunteers before and immediately after the first
      smoking of the water pipe and additionally after 6 hours. One and 2 weeks
      thereafter, blood was drawn again before and after smoking. A total of 7 blood
      samples was drawn during the study, and parameters of in vivo oxidation injury (8
      epi-PGF2alpha, malondialdehyde [MDA]) and haemostasis (11-dehydro-thromboxane B2
      [11-DH-TXB2]) were investigated. A single smoking session increased oxidation
      injury (8-epi-PGF2alpha: p=0.03; MDA: p=0.001) and 11-DH-TXB2 (p=0.00003)
      significantly, and repeated daily smoking induced a persistent long-lasting
      oxidation injury reflected by elevated prevalues but a smaller response to the
      actual water pipe smoke. These findings indicate a significant increase of in
      vivo oxidative stress by regular water pipe smoking.

PMID- 14575814
TI  - Real-time monitoring of nitric oxide in ischemic myocardium using an NO-selective
      electrode calibrated by electron spin resonance.
AB  - Using a Langendorff-perfused rat heart preparation and selective electrodes, we
      determined nitric oxide (NO) and oxygen levels in cardiac tissue. An NO-selective
      electrode that was calibrated by electron spin resonance (ESR) spectroscopy was
      inserted into the middle of the myocardium in the left ventricle. Simultaneously,
      we used an O2-selective electrode to measure the partial pressure of oxygen (pO2)
      in the perfusate, Krebs-Henseleit (K-H) solution, that was ejected from the
      heart. After 30 min of aerobic control perfusion, hearts were subjected to 30 min
      of global ischemia followed by 30 min of reperfusion. Under ischemic conditions,
      with a gradually decreasing pO2, NO detected by an NO-sensitive electrode within
      the myocardium was gradually increased. The maximum concentration increases in NO
      and decreases in pO2 during global ischemia were +10.200 +/- 1.223 microM and 
      58.608 +/- 4.123 mmHg, respectively. NO and pO2 levels both recovered to pre
      ischemia baseline values when perfusion was restarted after global ischemia
      (reperfusion). The presence of Nomega-nitro-L-arginine methyl ester (L-NAME, 10
      mM), a NOS inhibitor, prevented ischemia/reperfusion-induced changes in NO. This
      study shows that an NO-selective electrode that is calibrated by ESR can provide
      accurate, real-time monitoring of cardiac NO in normal and ischemic myocardium.

PMID- 14575813
TI  - Behavioral and biochemical studies on chronic mild stress models in rats treated
      with a Chinese traditional prescription Banxia-houpu decoction.
AB  - There is increasing evidence that psychological stress and depression trigger
      changes in various biochemical parameters in animals and in human subjects. In
      order to study these effects, the impact of chronic mild stress (CMS) on rats,
      and of the subsequent administration of Banxia-houpu decoction and fluoxetine,
      were studied regarding their effects on the following biochemical parameters: 5
      hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels in
      various brain regions, natural killer (NK) cell and lymphokine-activated killer
      (LAK) cell activities in spleen, serum lipid profiles including total cholesterol
      (TC), high density lipoprotein cholesterol (HDLc), low density lipoprotein
      cholesterol (LDLc) and triglyceride (TG), liver superoxide dismutase (SOD) and
      nitric oxide synthase (NOS) activities, serum malondialdehyde (MDA), and
      interleukin-2 (IL-2) levels. The effects of drug administration on preference
      behavior for consumption of sucrose solution were also assessed. Rats subjected
      to CMS exhibited a reduction in sucrose intake, 5-HT, 5-HIAA, IL-2, TC, HDLc and
      LDLc levels, as well as, diminished NK cell and LAK cell activities. Conversely,
      liver SOD and NOS activities and serum TG and MDA levels were increased following
      CMS exposures. Administration of Banxia-houpu decoction and fluoxetine produced
      beneficial effects on the stressed rats by improving sucrose consumption. This
      behavioral change was accompanied by amelioration of numbers CMS-induced
      biochemical changes. Banxia-houpu decoction is a traditional Chinese prescription
      containing pinellia tuber, magnolia bark, hoelen, perilla herb and ginger
      rhizome, and has been used for centuries in China to treat mental diseases
      including depression and schizophrenia. However, the pharmacological profile of
      the decoction is different from that of fluoxetine. These findings suggest that
      the therapeutic actions of Banxia-houpu decoction are due to a combination of
      multiple biochemical effects, and may help to elucidate the mechanisms through
      which distinct biochemical parameters play a role in the etiology of depression.

PMID- 14575815
TI  - A novel and potent biological antioxidant, Kinobeon A, from cell culture of
      safflower.
AB  - Kinobeon A was originally isolated from cultured cells of safflower (Carthamus
      tinctorius L., Compositae). It had never previously been directly isolated from
      safflower or other plants, animals or microorganisms. In this report, we
      demonstrate the anti-oxidative effects of kinobeon A and compare the results with
      those two known natural antioxidants, lignan (nordihydroguaiaretic acid) and
      quercetin. The NADPH-induced microsomal lipid peroxidation system was employed to
      assess anti-oxidative effects of kinobeon A. Addition of kinobeon A to the system
      significantly decreased the formation of thiobarbituric acid reactive substances
      (TBARS) in a dose-dependent manner with effects similar to those of lignan and
      quercetin. Formation of TBARS was completely inhibited at 10 microM of kinobeon
      A. Employing the xanthine/xanthine oxidase/nitroblue tetrazolium system and the
      KO2/XTT system, the superoxide anion scavenging activity of kinobeon A was
      greater than that of lignan or quercetin. IC50 values calculated for kinobeon A
      in these two systems were 1 microM and 0.8 microM, respectively. Kinobeon A
      exerted cytoprotective effects following oxidative treatments with hydrogen
      peroxide, cumene hydroperoxide, menadione and xanthine oxidase (XOD). Addition of
      kinobeon A to the systems markedly enhanced survival ratios of Madin-Darby bovine
      kidney cells, while their survival significantly decreased with the oxidative
      treatment alone. Kinobeon A exhibited stronger effect on the cell viability than
      lignan or quercetin when menadion or XOD were used as inducing reagents of
      oxidative stress. The present study demonstrates for the first time that kinobeon
      A prevents oxidative stresses and could be a useful cytoprotective reagent.

PMID- 14575816
TI  - Role of c-Myc in nitric oxide-mediated suppression of cytochrome P450 3A4.
AB  - Cytochrome P450 (CYP) 3A4, which is abundant in human liver and small intestine
      and participates in the metabolism of various drugs and xenochemicals, is known
      to be induced by 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in the colon carcinoma
      cell line Caco-2 cells. Nitric oxide (NO) is able to inhibit CYP3A4 expression
      and catalytic activity. In this study, we investigated the mechanism of
      suppression by NO of 1,25(OH)2D3-induced CYP3A4 expression in Caco-2 cells. Caco
      2 cells were exposed for 36 h to 400 nM 1,25(OH)2D3, and the induction of CYP3A4
      mRNA expression was detected by real-time PCR. Because c-Myc regulates the
      expression of several genes, we examined its effect on the CYP3A4 expression
      induced by 1,25(OH)2D3. The expression of c-myc mRNA was increased in the early
      stage but decreased 36 h after the treatment of Caco-2 cells with 1,25(OH)2D3.
      The NO donor NOR-4 suppressed CYP3A4 expression induced by 1,25(OH)2D3 in Caco-2
      cells in contrast, it significantly induced c-myc gene expression. Treatment of
      Caco-2 cells with the c-myc antisense oligonucleotide reversed the inhibitory
      effect of NOR-4 on CYP3A4 expression induced by 1,25(OH)2D3. These results
      suggest that the suppression of 1,25(OH)2D3-induced CYP3A4 expression by NO is
      due to c-myc expression.

PMID- 14575817
TI  - Evaluation of nitric oxide release in the coronary effluent by a novel EPR
      technique: a study on isolated rat hearts subjected to cold cardioplegia and
      reperfusion.
AB  - Aim of this study was to investigate the cardiac release of nitric oxide (NO)
      before and after cold cardioplegia by a novel electron paramagnetic resonance
      (EPR) technique. Isolated rat hearts were perfused for 20 min in a Langendorff
      apparatus and then subjected to 3 hours potassium-hypotermic cardioplegia,
      followed by 20 min reperfusion. The coronary effluent was collected in a flask
      containing ferrous-bis-diethyldithiocarbamate as a spin trap of NO. Since the
      trapping agent was not delivered to the heart with the perfusion medium, we
      avoided that an abnormal extraction of NO from the tissue could inhibit its
      biological activity. The EPR signal was well detectable after equilibration (25.6
      +/- 3.0 nmol/L +/- S.E.M.) and significantly increased following perfusion with
      10 micromol/L serotonin (41.1 +/- 3.2 nmol/L) or 10 micromol/L nitroprusside
      (43.5 +/- 2.9 nmol/L). The basal level of NO did not change after reperfusion,
      but serotonin administration was not able to stimulate its release. Serotonin
      failure to stimulate NO production was not due to a loss of endothelial NO
      synthase, since its protein expression was not modified after reperfusion. The
      perfusion pressure increased by 51% after reperfusion and was quite completely
      restored following serotonin or nitroprusside treatment, with respect to the non
      stimulated equilibration condition. Therefore, we suggest that the coronary spasm
      following a cold cardioplegic arrest is not due to an impaired production of
      basal NO and that NO-donors can be effective in relaxing vascular smooth muscle
      cells.

PMID- 14575818
TI  - Growth inhibition of human tumor cell lines by withanolides from Withania
      somnifera leaves.
AB  - Ayurvedic medicines prepared in India consist of Withania somnifera roots as one
      of the main ingredients. It is consumed as a dietary supplement around the world.
      The leaves of W. somnifera were used in the treatment of tumors and inflammation
      in several Asian countries. We have isolated twelve withanolides such as
      withaferin A (1), sitoindoside IX (2), 4-(1-hydroxy-2, 2-dimethylcyclpropanone)
      2, 3-dihydrowithaferin A (3), 2, 3-dihydrowithaferin A (4), 24, 25-dihydro-27
      desoxywithaferin A (5), physagulin D (1-->6)-beta-D-glucopyranosyl- (1-->4)-beta
      D-glucopyranoside (6), 27-O-beta-D-glucopyranosylphysagulin D (7), physagulin D
      (8), withanoside IV (9), and 27-O-beta-D-glucopyranosylviscosalactone B (10), 4,
      16-dihydroxy-5beta, 6beta-epoxyphysagulin D (11), viscosalactone B (12) from the
      leaves of this species. Compounds 1-12 and diacetylwithaferin A (13) were tested
      for their antiproliferative activity on NCI-H460 (Lung), HCT-116 (Colon), SF-268
      (Central Nervous System; CNS and MCF-7 (Breast) human tumor cell lines. The
      inhibitory concentration to afford 50% cell viability (IC50) for these compounds
      was determined by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium
      bromide) assay. Withaferin A and its derivatives exhibited inhibitory
      concentrations (50%) ranging from 0.24 +/- 0.01 to 11.6 +/- 1.9 microg/mL.
      Viscosalactone B (12) showed the 50% inhibition at concentrations ranging from
      0.32 +/- 0.05 to 0.47 +/- 0.15 microg/mL whereas its 27-O-glucoside derivative
      (10) exhibited IC50 between 7.9 +/- 2.9 and 17.3 +/- 3.9 microg/ml. However,
      Physagulin D type withanolides showed either weak or no activity at 30 microg/mL.
      Therefore, incorporation of withanolides in the diet may prevent or decrease the
      growth of tumors in human.

PMID- 14575819
TI  - Commentary on a multi-institutional analysis of external beam radiotherapy for T1
      T2 prostate cancer: "love the one you're with" and "do the right thing".

PMID- 14575820
TI  - Free speech and snake oil.

PMID- 14575821
TI  - Hypofractionation for prostate cancer radiotherapy--what are the issues?

PMID- 14575822
TI  - Long-term multi-institutional analysis of stage T1-T2 prostate cancer treated
      with radiotherapy in the PSA era.
AB  - PURPOSE: To report the long-term outcome for patients with Stage T1-T2
      adenocarcinoma of the prostate definitively irradiated in the prostate-specific
      antigen (PSA) era. METHODS AND MATERIALS: Nine institutions combined data on 4839
      patients with Stage T1b, T1c, and T2 adenocarcinoma of the prostate who had a
      pretreatment PSA level and had received >or=60 Gy as definitive external beam
      radiotherapy. No patient had hormonal therapy before treatment failure. The
      median follow-up was 6.3 years. The end point for outcome analysis was PSA
      disease-free survival at 5 and 8 years after therapy using the American Society
      for Therapeutic Radiology and Oncology (ASTRO) failure definition. RESULTS: The
      PSA disease-free survival rate for the entire group of patients was 59% at 5
      years and 53% at 8 years after treatment. For patients who had received >or=70
      Gy, these percentages were 61% and 55%. Of the 4839 patients, 1582 had failure by
      the PSA criteria, 416 had local failure, and 329 had distant failure. The
      greatest risk of failure was at 1.5-3.5 years after treatment. The failure rate
      was 3.5-4.5% annually after 5 years, except in patients with Gleason score 8-10
      tumors for whom it was 6%. In multivariate analysis for biochemical failure,
      pretreatment PSA, Gleason score, radiation dose, tumor stage, and treatment year
      were all significant prognostic factors. The length of follow-up and the effect
      of backdating as required by the ASTRO failure definition also significantly
      affected the outcome results. Dose effects were most significant in the
      intermediate-risk group and to a lesser degree in the high-risk group. No dose
      effect was seen at 70 or 72 Gy in the low-risk group. CONCLUSION: As follow-up
      lengthens and outcome data accumulate in the PSA era, we continue to evaluate the
      efficacy and durability of radiotherapy as definitive therapy for early-stage
      prostate cancer. Similar studies with higher doses and more contemporary
      techniques will be necessary to explore more fully the potential of this
      therapeutic modality.

PMID- 14575823
TI  - Comparison of alternative biochemical failure definitions based on clinical
      outcome in 4839 prostate cancer patients treated by external beam radiotherapy
      between 1986 and 1995.
AB  - PURPOSE: To assess the merit of the American Society for Therapeutic Radiology
      and Oncology (ASTRO) definition of biochemical failure after external beam
      radiotherapy for prostate cancer by testing alternative prostate-specific antigen
      (PSA) failure definitions against the "gold standard" of clinical failure and to
      study the effect of backdating the time of failure. METHODS AND MATERIALS: Nine
      participating institutions agreed to submit follow-up results for all patients
      with clinically localized prostatic cancer (Stage T1b, T1c, T2, N0M0) treated
      between 1986 and 1995 by external beam radiotherapy only, to doses of >or=60 Gy,
      with no androgen deprivation before treatment. A total of 4839 men met the study
      criteria, with a median follow-up time of 6.3 years. The prediction of clinical
      failure by 102 definitions of biochemical failure was assessed using various
      quantitative measures. RESULTS: Four definitions were superior as measured by the
      sensitivity, specificity, positive and negative predictive values, and hazard of
      clinical failure after biochemical failure: two rises of at least 0.5 ng/mL
      backdated, PSA level at or greater than the absolute nadir plus 2 ng/mL at the
      call date, and PSA level at or greater than the current nadir plus 2 or 3 ng/mL
      at the call date. The absolute nadir was the lowest measured PSA level during all
      of follow-up, and the current nadir was the lowest PSA measured previous to a
      particular PSA measurement during follow-up. With the possible exception of
      patients in the low-risk group, the likelihood of ultimate clinical failure
      decreased as the time of biochemical failure increased. Failure definitions based
      on PSA levels >0.2 or 0.5 ng/mL were inferior to other definitions. Backdating
      the failure time introduced bias into the estimate of freedom from biochemical
      failure, which was increasingly overestimated at shorter median follow-up times.
      This bias can be circumvented either by using a failure definition based on the
      call date or by backdating the censoring times of patients with one or two rises
      who could potentially have failure at a future (unobserved) time. A short follow
      up time as such does not result in bias unless the failures are backdated; in the
      absence of backdating, it is the precision of failure-free survival that is
      increasingly compromised as the follow-up time is reduced. CONCLUSION: The ASTRO
      failure definition ended the confusion resulting from different failure
      definitions that had been in use, and it did so accurately enough that it is
      probably not necessary to recalculate previously published results. Nevertheless,
      for the current pooled analysis of outcome in 4839 men with a 6.3-year median
      follow-up, other definitions of biochemical failure were superior as assessed by
      various quantitative measures of concordance of biochemical and ultimate clinical
      failure. An additional disadvantage of the ASTRO definition is the bias
      introduced by backdating failures, as well as the necessarily retrospective
      nature of its application. Some "current" definitions, but not those based on the
      PSA level rising above a fixed threshold, have significantly higher sensitivity
      and specificity, do not lead to biased estimations of biochemical disease-free
      survival, and are directly applicable during patient counseling. These are all
      issues that would play a role in replacing the ASTRO consensus definition.

PMID- 14575824
TI  - Ten-year biochemical relapse-free survival after external beam radiation and
      brachytherapy for localized prostate cancer: the Seattle experience.
AB  - PURPOSE: The role of external beam radiation therapy in addition to brachytherapy
      continues to be scrutinized for long term control of PSA levels after prostate
      cancer diagnosis. METHODS AND MATERIALS: We report 10-year biochemical relapse
      free survival (BRFS) on 232 patients presenting with localized prostate cancer
      and consecutively treated with iodine(125) (I(125)) or palladium(103) (Pd(103))
      brachytherapy and neoadjuvant external beam radiation therapy. Multivariate
      regression analysis was used to create a pretreatment clinical prognostic risk
      model using a modified ASTRO consensus definition (two consecutive rises in serum
      PSA) as the outcome. Gleason scoring was performed by pathologists at a small
      community hospital. Derived risk categories are the following: low = PSA <or=10
      ng/mL, Gleason sum score <7, and stage <T2c; intermediate = PSA >10 ng/mL or
      Gleason Score >or=7 or stage >or=T2c (1 intermediate risk factor); and high = 2
      or more intermediate risk factors. Time to PSA failure (local, distant, or
      biochemical) was calculated and compared using Kaplan-Meier plots. RESULTS: Ten
      year BRFS for the entire treatment group was 70%. Biochemical control rates by
      risk cohort analysis (95% confidence interval): low risk, 85% (83.3-90.7%);
      intermediate risk, 77% (73.0-84.5%); and high risk, 45% (45.4-57.2%). Using a
      risk grouping proposed by the Mt. Sinai group, the BRFS was: low risk, 84%;
      intermediate risk, 93%; and high risk, 57%. Grouping by the risk classification
      used by D'Amico, the BRFS was: low risk, 86%; intermediate risk, 90%; and high
      risk, 48%. CONCLUSIONS: I(125) or Pd(103) brachytherapy, as a boost combined with
      EBRT, continues to result in high rates of biochemical control at 10 years.
      Different risk group classification schemes lead to different BRFS results.

PMID- 14575825
TI  - Rectal dose-volume constraints in high-dose radiotherapy of localized prostate
      cancer.
AB  - PURPOSE: To investigate the relationship between rectal bleeding and dosimetric
      clinical parameters in patients receiving three-dimensional conformal
      radiotherapy (3D-CRT) for localized prostate cancer. METHODS: In a retrospective
      national study (AIROPROS01-01, AIRO: Associazione Italiana Radioterapia
      Oncologica), planning/clinical data for 245 consecutive patients with stage T1
      4N0-x prostate carcinoma who underwent 3D-CRT to 70-78 Gy (ICRU point) were
      pooled from four Italian institutions. The correlation between late rectal
      bleeding and rectal dose-volume data (the percentage of rectum receiving more
      than 50, 55, 60, 65, 70, and 75 Gy [V(50-70)]) and other dosimetric and clinical
      parameters were investigated in univariate (log-rank) and multivariate (Cox
      regression model) analyses. Median follow-up was 2 years. RESULTS: Twenty-three
      patients were scored as late bleeders according to a modified RTOG definition
      (Grade 2: 16; Grade 3: 7); the actuarial 2-year rate was 9.2%. Excepting V75, all
      median and third quartile V(50-70) values were found to be significantly
      correlated with late bleeding at univariate analysis. The smallest p value was
      seen for V(50) below/above the third quartile value (66%). The V70 (cut-off
      value: 30%) was found to be also predictive for late bleeding. In the high-dose
      subgroup (74-78 Gy), Grade 3 bleeding was highly correlated with this constraint.
      The predictive value of both V(50) and V(70) was confirmed by multivariate
      analyses. CONCLUSIONS: The present article provides evidence for correlation
      between rectal DVH parameters and late rectal bleeding in patients treated with
      curative intent with 3D-CRT. To keep the rate of moderate/severe rectal bleeding
      below 5-10%, it seems advisable to limit V(50) to 60-65%, V(60) to 45-50%, and
      V70 to 25-30%.

PMID- 14575826
TI  - Utility of the percentage of positive prostate biopsies in predicting PSA outcome
      after radiotherapy for patients with clinically localized prostate cancer.
AB  - PURPOSE: To determine the utility of the percentage of positive prostate biopsies
      (PPPB) in predicting prostate-specific antigen (PSA) outcome after external beam
      radiotherapy alone. METHODS AND MATERIALS: The records of 750 clinical Stage T1
      and T2 patients treated by external beam radiotherapy alone with a median follow
      up of 80 months were reviewed. Of the 750 patients, 345 were eligible for
      analysis; 255 (74%) had undergone sextant biopsies, 28 (8%) <6 biopsies, and 62
      (18%) >6 biopsies. The pretreatment PSA level (<10, 10-20, >20 ng/mL), biopsy
      Gleason score (2-6, 7, 8-10), and clinical stage (T1-T2a, T2b, T2c), uni- or
      bilateral positive biopsy, radiation dose, and PPPB were analyzed as potential
      predictors of PSA outcome. The PPPB data were analyzed as a continuous and as a
      categorical variable. RESULTS: PPPB was a significant predictor of the time to
      PSA failure on univariate analysis as a continuous (p = 0.0053) and as a
      categorical (<50% vs. >or=50%, p = 0.0077) variable. In multivariate analysis, a
      trend was noted for worse 5-year PSA failure-free survival based on PPPB >or=50%
      vs. <50% (p = 0.082). Sixty-four patients experienced biochemical failure
      according to the American Society for Therapeutic Radiology Oncology definition.
      The 5-year PSA failure-free survival rate was 79% vs. 69% (p = 0.02) and the
      clinical disease-free survival rate was 97% vs. 86% (p = 0.0004) for patients
      with <50% vs. >or=50% PPPB. PPPB was not a significant predictor for the time to
      PSA failure within the traditional risk groups (low, intermediate, and high) on
      multivariate analysis. CONCLUSION: PPPB was a predictor of post-external beam
      radiotherapy PSA outcome in clinically localized prostate cancer; but in this
      cohort it did not provide additional information beyond the traditional risk
      stratification schema.

PMID- 14575828
TI  - Predictors of reexcision findings and recurrence after breast conservation.
AB  - PURPOSE: To identify predictors of reexcision findings and local recurrence in
      the setting of breast-conserving therapy with radiation. METHODS: The records of
      535 patients who underwent breast-conserving surgery followed by radiation for
      Stage I or II cancer between 1972 and 1996 were reviewed. The mean follow-up
      period for surviving patients without evidence of recurrence is 6 years. Various
      clinical and pathologic prognostic factors were examined for significance with
      regard to reexcision findings and recurrence rates. Pathologic margin status was
      classified as negative, close (<or=2 mm), positive, or indeterminate. RESULTS:
      The pathologic margin status was the most important predictor of local
      recurrence. The freedom from local relapse (FFLR) at 6 years was 97% for patients
      with negative pathologic margins and 86% for all others (p < 0.0001). There was
      no significant difference in recurrence rates among patients with close,
      positive, or indeterminate margins. However, the use and sequencing of systemic
      therapy affected recurrence rates among these patients. For patients with close,
      positive, or indeterminate margins, the crude risk of local recurrence was 4%
      among patients who received tamoxifen or received chemotherapy integrated with or
      after radiation. The risk of local recurrence was 16-29% among the patients with
      close, positive, or indeterminate margins who did not receive systemic therapy or
      who received radiation after completion of chemotherapy. Local recurrence rates
      were low in patients with negative margins (2-8%) regardless of the use of
      systemic therapy or its timing. The presence or absence of residual disease at
      reexcision did not predict recurrence as long as the final margins were negative.
      Among patients who underwent reexcision before radiation, extensive intraductal
      component (EIC) (p = 0.0001) and young patient age (p = 0.03) were predictive of
      residual disease in the specimen. Patients with initially close margins and no
      EIC had a low risk of residual disease at the time of reexcision, as did patients
      older than age 65 without EIC. CONCLUSION: Pathologic margin status is the most
      important predictor of local recurrence after breast conservation with radiation.
      Patient age and EIC were significant predictors of residual disease at
      reexcision. The use and timing of systemic therapy appear to influence the risk
      of local recurrence in patients who do not have negative lumpectomy margins.

PMID- 14575827
TI  - Three-dimensional evaluation of intra- and interfraction immobilization of lung
      and chest wall using active breathing control: a reproducibility study with
      breast cancer patients.
AB  - PURPOSE: A CT-based three-dimensional (3D) method was used to analyze the intra-
      and interfraction reproducibility of lung immobilization during moderate deep
      inspiration breath hold (mDIBH), defined as 75% of the maximal inspiration using
      an active breathing control (ABC) apparatus. METHODS AND MATERIALS: The ABC
      apparatus was used to immobilize the breathing motion with a computer-controlled
      valve. Immobilization of the lungs in breast cancer patients was used as a model
      to evaluate the reproducibility of mDIBH using the ABC apparatus. CT scans were
      acquired twice at mDIBH in the same session for 30 breast cancer patients. Twenty
      three of them were immobilized with an alpha-cradle, of which 14 had a repeat
      scan at mDIBH 1-4 weeks later. Twelve of those patients received intensity
      modulated radiotherapy to the left breast at mDIBH to displace the heart from the
      beam. The remaining patients were treated at free breathing, with either
      intensity-modulated irradiation to the whole breast or conformal partial breast
      irradiation. To remove the component of setup error, mDIBH scans were registered
      with respect to the vertebrae. The lungs and carina were auto-contoured to form
      3D surfaces for each data set. The closest distance-to-agreement (DTA) for each
      point between the 3D surfaces of the corresponding CT scans was displayed on a 3D
      surface map. For analysis, each lung was divided along its inferior to superior
      extent into six regions, from the basal 10%, the next four consecutive 20%
      sections in height, to the last apical 10%. Likewise, the carina was divided into
      regions of the trachea and bifurcation. The mean and standard deviation (SD) of
      the DTA for each of these regions was computed. RESULTS: With the patient
      positioned in an alpha-cradle, the mean +/- SD intrafraction DTA was 1.5 +/- 1.4
      mm for the left lung and 1.0 +/- 1.4 mm for the right lung. The corresponding
      values without the use of an alpha-cradle were significantly greater, with 1.9 +/
      2.1 mm and 2.2 +/- 2.2 mm for the left and right lung, respectively (p <0.005
      for the SD of the left lung and p <0.0003 for the SD of the right lung). The
      interfraction DTA for the left and right lungs was 1.4 +/- 1.7 mm and 1.4 +/- 1.6
      mm, respectively. The regional analysis demonstrated better immobilization for
      the upper two-thirds of the chest wall compared with that for the lung base. The
      DTA values obtained for the tracheal bifurcation were 0.9 +/- 0.8 mm for
      intrafraction and 1.4 +/- 1.0 mm for interfraction. CONCLUSION: The ABC device
      can be used to reduce respiratory motion at mDIBH in breast cancer patients or
      those patients who can perform the maneuver. This device demonstrated excellent
      intra- and interfraction reproducibility of chest wall and carina immobilization,
      especially when combined with alpha-cradle immobilization. Internal margins for
      suspended breathing can be extrapolated from these data for various anatomic
      regions within the lung and chest wall.

PMID- 14575829
TI  - Cyclin A and Ki-67 expression as predictors for locoregional recurrence and
      outcome in laryngeal cancer patients treated with surgery and postoperative
      radiotherapy.
AB  - PURPOSE: To investigate the association between the cancer cell proliferation
      fraction and the risk of recurrence in laryngeal cancer patients treated without
      systemic therapy. METHODS AND MATERIALS: Paraffin-embedded tumor samples from 90
      laryngeal cancer patients were stained for cyclin A and the Ki-67 antigen by
      immunohistochemistry. The patients were treated with partial or total
      laryngectomy followed by postoperative radiotherapy to a total dose of 50 Gy or
      greater. The median follow-up time was 91 months (minimum 48 months). RESULTS:
      High cyclin A expression (>19% positive cancer cell nuclei, the highest tertile)
      was associated with a high rate of locoregional tumor recurrence and unfavorable
      disease-free and overall survival as compared with cases with a lower expression
      (p = 0.025, 0.032, and 0.042, respectively). In a multivariate analysis, high
      cyclin A expression was an independent predictor of poor disease-free survival
      (RR 2.4, 95% CI 1.2-4.9, p = 0.013) and overall survival (RR 2.1, 1.2-3.6, p =
      0.012), together with a poor Karnofsky's performance status and the presence of
      positive margins at surgery. Ki-67 expression was not an independent predictor of
      survival, but cancers with high Ki-67 expression (>34% nuclei positive, the
      highest tertile) recurred more frequently locoregionally when treated with split
      course radiotherapy than when treated with a continuous course of therapy (p =
      0.035), whereas the presence of a planned split did not influence the frequency
      of locoregional recurrences when Ki-67 expression was lower (p = 0.93).
      CONCLUSION: Cancer cell cyclin A expression is a novel predictive factor for
      outcome in laryngeal cancer treated with surgery and postoperative radiotherapy.
      Planned gaps in the radiotherapy course are deleterious in patients with a high
      proliferative fraction, and immunostaining for the Ki-67 antigen may be useful in
      identification of such patients.

PMID- 14575830
TI  - Fractionated stereotactic radiotherapy in low-grade astrocytomas: long-term
      outcome and prognostic factors.
AB  - PURPOSE: To evaluate outcome after fractionated stereotactic radiotherapy (RT) of
      patients with World Health Organization Grade 2 astrocytoma in terms of
      progression-free survival, overall survival, toxicity, quality of life, and
      prognostic factors. METHODS AND MATERIALS: Between 1984 and 2000, 143 patients
      with histologically proven Grade 2 astrocytoma were treated with fractionated
      stereotactic RT at our institution. The evaluation of the quality of life and
      toxicity was based on neurologic examinations and the Karnofsky performance
      score. Univariate analysis was performed on seven potential prognosticators and
      multivariate analysis on four prognosticators. RESULTS: The median follow-up was
      44 months. The actuarial overall survival and progression-free survival was 58%
      and 39% at 5 years, respectively. Out-of-field recurrences occurred in 1 patient
      (1.2%). We did not observe a dose-response relationship. Overall survival and
      progression-free survival were significantly correlated with the absence of
      contrast media enhancement before RT (p <0.01). Toxicity was mild and included
      severe side effects of European Organization for Research and Treatment of
      Cancer/Radiation Therapy Oncology Group Grade 3 in only 4 patients (2.8%). The
      Karnofsky performance score improved in most patients. CONCLUSION: Fractionated
      stereotactic RT is effective and has low toxicity in the treatment of Grade 2
      gliomas. The rate of field border recurrences was not increased compared with
      after conventional RT. Exceeding the tumor dose did not improve the tumor control
      rate but did enhance toxicity. Pretherapeutic contrast media enhancement should
      be interpreted as a sign of higher grade tumor elements.

PMID- 14575831
TI  - Outcome and pattern of failure in pathologic stage I-II papillary serous
      carcinoma of the endometrium: implications for adjuvant radiation therapy.
AB  - PURPOSE: To evaluate the outcome and patterns of failure in women with pathologic
      Stage I-II papillary serous carcinoma of the uterus and to discuss the
      implications for adjuvant radiation therapy (RT). METHODS: Twenty-three
      pathologic Stage I-II uterine papillary serous carcinoma patients were treated at
      our institution between 1980 and 2001. All underwent total abdominal hysterectomy
      and bilateral salpingo-oophorectomy and assessment of peritoneal cytology. Pelvic
      and para-aortic lymph node sampling was performed in 12 and 8 patients,
      respectively. FIGO stages were as follows: IA = 3, IB = 8, IC = 6, IIA = 5, and
      IIB = 1. Adjuvant therapies included the following: 9 none, 10 RT (6 pelvic, 1
      vaginal brachytherapy, 3 both), 4 chemotherapy, and 1 hormonal therapy. No
      patient received whole abdominal radiation therapy or para-aortic RT. Disease
      free survival, pelvic recurrence-free survival, and cause-specific survival were
      estimated using the method of Kaplan-Meier, and prognostic factors were analyzed
      by the log-rank test. Median follow-up was 38.7 months (range: 3-109 months).
      RESULTS: The 5-year actuarial disease-free survival and cause-specific survival
      for the entire group was 41% and 73.6%, respectively. Nine patients developed
      recurrent disease. Five failed in the pelvis, of which 4 relapsed in the vagina.
      No pelvic failures occurred in women treated with adjuvant RT. Patients treated
      with adjuvant RT had a better 5-year actuarial pelvic recurrence-free survival
      (100% vs. 57.5%, p = 0.06) than patients treated with surgery alone. Two patients
      failed in the abdomen. However, neither developed an isolated abdominal
      recurrence. Six patients failed in distant sites, primarily the lungs and bone.
      CONCLUSION: Although patients with pathologic Stage I-II uterine papillary serous
      carcinomas have organ-confined disease, recurrence is common, particularly in the
      pelvis and distant sites. Our results suggest that adjuvant RT reduces the risk
      of pelvic failure. Contrary to traditional assumptions, however, abdominal
      recurrence was uncommon in our patients, despite the lack of whole abdominal
      radiation therapy. Our results support the use of pelvic RT in these patients.
      Future studies should investigate the role of adjuvant chemotherapy.

PMID- 14575832
TI  - Unique role of proximal rectal dose in late rectal complications for patients
      with cervical cancer undergoing high-dose-rate intracavitary brachytherapy.
AB  - PURPOSE: To investigate the correlation of the radiation dose to the upper
      rectum, proximal to the International Commission of Radiation Units and
      Measurements (ICRU) rectal point, with late rectal complications in patients
      treated with external beam radiotherapy (EBRT) and high-dose-rate (HDR)
      intracavitary brachytherapy (ICRT) for carcinoma of the uterine cervix. METHODS
      AND MATERIALS: Between June 1997 and February 2001, 75 patients with cervical
      carcinoma completed definitive or preoperative RT and were retrospectively
      reviewed. Of the 75 patients, 62 with complete dosimetric data and a minimal
      follow-up of at least 1 year were included in this analysis. Of the 62 patients,
      36 (58%) also received concurrent chemotherapy, mainly with cisplatin during
      EBRT. EBRT consisted of a mean of 50.1 +/- 1.3 Gy of 18-MV photons to the pelvis.
      A parametrial boost was given to 55 patients. Central shielding was used after 40
      45 Gy of pelvic RT. HDR ICRT followed EBRT, with a median dose of 5 Gy/fraction
      given twice weekly for a median of four fractions. The mean dose to point A from
      HDR ICRT was 23.9 +/- 3.0 Gy. In addition to the placement of a rectal tube with
      a lead wire during ICRT, 30-40 mL of contrast medium was instilled into the
      rectum to demonstrate the anterior rectal wall up to the rectosigmoid junction.
      Late rectal complications were recorded according to the Radiation Therapy
      Oncology Group grading system. The maximal rectal dose taken along the rectum
      from the anal verge to the rectosigmoid junction and the ICRU rectal dose were
      calculated. Statistical tests were used for the correlation of Grade 2 or greater
      rectal complications with patient-related variables and dosimetric factors.
      Correlations among the point A dose, ICRU rectal dose, and maximal proximal
      rectal dose were analyzed. RESULTS: Fourteen patients (23%) developed Grade 2 or
      greater rectal complications. Patient-related factors, definitive or preoperative
      RT, and the use of concurrent chemotherapy were not associated with the
      occurrence of rectal complications. The maximal rectal dose during ICRT was at
      the proximal rectum rather than at the ICRU rectal point in 55 (89%) of 62
      patients. Patients with Grade 2 or greater rectal complications had received a
      significantly greater total maximal proximal rectal dose from ICRT (25.6 Gy vs.
      19.2 Gy, p = 0.019) and had a greater maximal proximal rectal dose/point A dose
      ratio (1.025 vs. 0.813, p = 0.024). In contrast, patients with and without rectal
      complications had a similar dose at point A (25.0 Gy vs.23.6 Gy, p = 0.107). The
      differences in the ICRU rectal dose (17.8 Gy vs.15.4 Gy, p = 0.065) and the ICRU
      rectal dose/point A dose ratio (0.71 vs. 0.66, p = 0.210) did not reach
      statistical significance. Patients with >62 Gy of a direct dose sum from EBRT and
      ICRT to the proximal rectum (12 of 29 vs. 2 of 33, p = 0.001) and >110 Gy of a
      total maximal proximal rectal biologic effective dose (13 of 40 vs. 1 of 22, p =
      0.012) presented with a significantly increased frequency of Grade 2 or greater
      rectal complications. The correlations between the maximal proximal rectal dose
      and the ICRU rectal dose were less satisfactory (Pearson coefficient 0.375).
      Moreover, 11 of the 14 patients with rectal complications had colonoscopic
      findings of radiation colitis at the proximal rectum, the area with the maximal
      rectal dose. CONCLUSION: Eighty-nine percent of our patients had a maximal rectal
      dose from ICRT at the proximal rectum instead of the ICRU rectal point. The
      difference between patients with and without late rectal complications was more
      prominent for the proximal rectal dose than for the ICRU rectal dose. It is
      important and useful to contrast the whole rectal wall up to the rectosigmoid
      junction and to calculate the dose at the proximal rectum for patients undergoing
      HDR ICRT.

PMID- 14575834
TI  - Evaluation of the National Resident Matching Program (NRMP) radiation oncology
      data (1993-2003).
AB  - PURPOSE: Radiation oncology continues to evolve as a specialty. In the early
      1990s, issues of manpower oversupply, resource allocation, development of
      academic radiation oncology, and residency training curricula were fervently
      considered and evaluated. Much of this effort continues. This communication
      endeavors to examine the National Residency Matching Program (NRMP) results as
      they pertain to radiation oncology to identify and document applicant trends over
      the last decade. METHODS AND MATERIALS: The NRMP database tables for inclusive
      dates 1993-2003 were evaluated. The database figures were supplied directly from
      the executive staff at the AAMC/NRMP. Data were reviewed for radiation oncology,
      and the following variables were evaluated for the study period (1993-2003):
      Training program participation, positions offered, applicant totals, proportion
      of US senior applicants, US seniors as a percentage of those who successfully
      matched, ratio of applicants to positions, and percentage of training program
      positions filled. Trends over the study period were analyzed. Data were also
      analyzed for all specialties collectively as a comparison group. RESULTS: The
      number of training programs has remained relatively stable between 1993 and 2003.
      In 2003, each radiation oncology program in the NRMP on average accepted two new
      candidates. The number of positions offered has fluctuated over time. There
      appeared to be a downward trend until 2003, during which 107 positions were
      offered. The number of applicants continues to rise with totals of 209 and 214 in
      2003 and 2001, respectively. Percentage of US senior applicants compared with the
      total pool has remained relatively stable, but raw numbers are rising. The number
      of US seniors as a percentage of those who successfully matched escalated during
      2001 compared with previous years. This value has been consistent over the past 3
      years, at a level of approximately 94%. The ratio of applicants to positions,
      which is a broad indicator of level of competition for entrance, began to rise
      significantly in 2000 to a level of 1.9. It peaked at 2.6 in 2001, and the ratio
      for 2003 was approximately 2.0. For the first time, all positions offered were
      filled (100%) through the NRMP match process in 2003. Such positive trends have
      not been realized to the same degree for all specialties analyzed as a cohort.
      CONCLUSION: Acceptance into radiation oncology training programs through the NRMP
      has become very competitive. The explanation for this trend is likely complex
      with many variables. These data may be helpful in training program development
      and will certainly be of service to advisors of medical students seeking entrance
      into the field in the near future.

PMID- 14575833
TI  - Whole abdominopelvic radiotherapy (WAPRT) using intensity-modulated arc therapy
      (IMAT): first clinical experience.
AB  - PURPOSE: Whole abdominopelvic radiation therapy (WAPRT) is a treatment option in
      the palliation of patients with relapsed ovarian cancer. With conventional
      techniques, kidneys and liver are the dose- and homogeneity-limiting organs. We
      developed a planning strategy for intensity-modulated arc therapy (IMAT) and
      report on the treatment plans of the first 5 treated patients. METHODS AND
      MATERIALS: Five consecutive patients with histologically proven relapsed ovarian
      cancer were sent to our department for WAPRT. The target volumes and organs at
      risk (OAR) were delineated on 0.5-cm-thick CT slices. The clinical target volume
      (CTV) was defined as the total peritoneal cavity. CTV and kidneys were expanded
      with 0.5 cm. In a preset range of 8 degrees interspaced gantry angles, machine
      states were generated with an anatomy-based segmentation tool. Machine states of
      the same class were stratified in arcs. The optimization of IMAT was done in
      several steps, using a biophysical objective function. These steps included
      weight optimization of machine states, leaf position optimization adapted to meet
      the maximal leaf speed constraint, and planner-interactive optimization of the
      start and stop angles. The final control points (machine states plus associated
      cumulative monitor unit counts) were calculated using a collapsed cone
      convolution/superposition algorithm. For comparison, two conventional plans
      (CONV) were made, one with two fields (CONV2), and one with four fields (CONV4).
      In these CONV plans, dose to the kidneys was limited by cerrobend blocks. The
      IMAT and the CONV plans were normalized to a median dose of 33 Gy to the planning
      target volume (PTV). Monomer/polymer gel dosimetry was used to assess the
      dosimetric accuracy of the IMAT planning and delivery method. RESULTS: The median
      volume of the PTV was 8306 cc. The mean treatment delivery time over 4 patients
      was 13.8 min. A mean of 444 monitor units was needed for a fraction dose of 150
      cGy. The fraction of the PTV volume receiving more than 90% of the prescribed
      dose (V(90)) was 9% higher for the IMAT plan than for the CONV4 plan (89.9% vs.
      82.5%). Outside a build-up region of 0.8 cm and 1 cm away from both kidneys, the
      inhomogeneity in the PTV was 15.1% for the IMAT plans and 24.9% for the CONV4
      plans (for CONV2 plans, this was 34.9%). The median dose to the kidneys in the
      IMAT plans was lower for all patients. The 95th percentile dose for the kidneys
      was significantly higher for the IMAT plans than for the CONV4 and CONV2 plans
      (28.2 Gy vs. 22.2 Gy and 22.6 Gy for left kidney, respectively). No relevant
      differences were found for liver. The gel-measured dose was within clinical
      planning constraints. CONCLUSION: IMAT was shown to be deliverable in an
      acceptable time slot and to produce dose distributions that are more homogeneous
      than those obtained with a CONV plan, with at least equal sparing of the OARs.

PMID- 14575835
TI  - Disparate effects of endostatin on tumor vascular perfusion and hypoxia in two
      murine mammary carcinomas.
AB  - PURPOSE: Recent results in the literature have demonstrated that the
      antiangiogenic agent endostatin can enhance antitumor effects when administered
      before or during radiotherapy. To better understand the underlying
      pathophysiologic basis for this radiosensitization, the current study
      investigated whether short-term endostatin administration is linked to
      alterations in tumor vascular perfusion and oxygen delivery. METHODS AND
      MATERIALS: Three daily doses of recombinant endostatin (20 mg/kg) were
      administered to two murine mammary carcinomas, the highly vascularized MCa-35 and
      the less vascularized MCa-4. Image analysis techniques were used to quantify (1)
      total and perfused vascular spacing, and (2) changes in tumor hypoxia as a
      function of distance from the nearest blood vessel. RESULTS: In MCa-35 tumors,
      endostatin had no effect on vessel spacing, tumor hypoxia, or tumor growth. In
      MCa-4 tumors, total and perfused vessel spacings were also unchanged, but tumor
      growth was inhibited, and tumor hypoxia significantly decreased. These tumors
      demonstrated an increased vascular functionality suggestive of an increase in the
      number of intermittently perfused vessels, without corresponding alterations in
      tumor oxygen consumption rate. CONCLUSIONS: Poorly vascularized, hypoxic mammary
      carcinomas were much more responsive to short-term endostatin treatment than well
      vascularized, more homogeneously oxygenated tumors. Oxygen levels in the
      responsive tumors were transiently improved after treatment, which could have
      substantial implications with respect to the therapeutic effectiveness of
      combining antiangiogenic agents with conventional therapies.

PMID- 14575836
TI  - Vascular targeting effects of ZD6126 in a C3H mouse mammary carcinoma and the
      enhancement of radiation response.
AB  - PURPOSE: The aim of this study was to investigate the pathophysiologic effects
      induced by the novel vascular targeting agent ZD6126 in a C3H mouse mammary
      carcinoma and to evaluate the agent's ability to inhibit tumor growth either when
      given alone or in combination with radiation. METHODS AND MATERIALS: A C3H
      mammary carcinoma grown in the right rear foot of female CDF1 mice was treated
      when at 200 mm(3) in size. ZD6126 was dissolved in saline and injected
      intraperitoneally. Blood perfusion was measured using the RbCl extraction
      procedure, tumor oxygen (pO(2)) status was assessed with the Eppendorf electrode,
      and tumor necrosis was estimated from histologic sections. Radiation (240-kV X
      rays) was locally administered to tumors of restrained nonanesthetized mice, and
      response was assessed using a tumor growth assay. RESULTS: ZD6126 induced a
      significant dose- and time-dependent decrease in tumor perfusion, reaching a
      maximal 70% reduction around 3 h after injecting 150-300 mg/kg. However, full
      recovery was seen within 6 h. A 200 mg/kg dose significantly decreased tumor
      oxygenation status at 3 h (median pO(2) decreased from 7 to 3 mm Hg; % pO(2)
      values <or=2.5 mm Hg increased from 30% to 55%) and by 24 h had significantly
      increased necrotic fraction from 14.5% to 25.2%. This ZD6126 dose resulted in a
      small, yet significant, 1.4 days inhibition of tumor growth when given alone. It
      also enhanced the tumor response to radiation, giving rise to a significant 1.3
      fold increase in the slope of the radiation dose-response curve. Of the normal
      tissues, only muscle (at 3 h) and spleen (at 6 h) showed any significant
      reduction in perfusion after injecting 200 mg/kg, but these transient decreases
      were only 32% and 49%, respectively. CONCLUSIONS: Our preclinical studies clearly
      demonstrate a tumor-specific reduction in blood perfusion by ZD6126. Although
      these changes were transient, they were sufficient to increase tumor necrosis,
      inhibit tumor growth, and enhance radiation response.

PMID- 14575837
TI  - Overexpression of extracellular superoxide dismutase protects mice from radiation
      induced lung injury.
AB  - PURPOSE: The purpose of this study was to determine if radiation-induced lung
      injury is associated with prolonged oxidative stress, and whether chronic
      overexpression of extracellular superoxide dismutase (EC-SOD) in the lung of
      transgenic mice protects against radiation-induced lung injury. METHODS AND
      MATERIALS: Whole-lung radiation was delivered to EC-SOD overexpressing B6C3
      transgenic (XRT-TG) mice and wild-type littermates (XRT-WT). Pulmonary function
      was assessed by breathing frequency. Right lung wet weight was used as a gross
      indicator of lung damage. Histopathology was used to assess collagen deposition
      and tissue fibrosis according to an established grading system.
      Immunohistochemistry was used to stain and quantify the number of macrophages.
      ELISA was used to measure activated TGF-beta1. Oxidative stress was assessed by
      measuring lipid oxidation products (malondialic acid) by HPLC. RESULTS: Four of
      six XRT-WT mice required euthanasia at 15-19 weeks postradiation because of
      respiratory distress, whereas no XRT-TG mouse developed distress. All assessments
      of lung damage at 15-20 weeks postradiation were higher for XRT-WT mice compared
      with the XRT-TG mice, including breathing frequency (380 vs. 286 bpm, p <or=
      0.0004), right lung weight (228 vs. 113 mg, p <or= 0.06), macrophage count (48
      vs. 5 per 40x field, p <or= 0.06), and percent activated TGF-beta1 (37 vs. 11%, p
      <or= 0.06). Semiquantitative measures, including fibrosis and collagen
      deposition, were also higher for XRT-WT mice, with an exact Fisher p value of
      <or=0.03 for both variables. In addition, malondialic acid was elevated in XRT-WT
      mice 15-20 weeks after radiation delivery, and levels were lower in the XRT-TG
      mice (624 vs. 323 pmol/mg protein, p <or= 0.06). CONCLUSIONS: After radiation
      therapy, oxidative stress is present at 15-20 weeks after initial exposure, which
      correlates with the delayed clinical onset of radiation-induced lung damage.
      Overexpression of EC-SOD in transgenic mice appears to confer protection against
      this radiation-induced lung injury, with a corresponding decrease in oxidative
      stress. EC-SOD may be a potential therapeutic agent for radioprotection in the
      treatment of thoracic malignancies. Further investigation is needed to confirm
      and expand on the current results.

PMID- 14575838
TI  - Citrulline: a physiologic marker enabling quantitation and monitoring of
      epithelial radiation-induced small bowel damage.
AB  - PURPOSE: Small bowel irradiation results in epithelial cell loss and consequently
      impairs function and metabolism. We investigated whether citrulline, a metabolic
      end product of small bowel enterocytes, can be used for quantifying radiation
      induced epithelial cell loss. METHODS AND MATERIALS: NMRI mice were subjected to
      single-dose whole body irradiation (WBI). The time course of citrullinemia was
      assessed up to 11 days after WBI. A dose-response relationship was determined at
      84 h after WBI. In addition, citrullinemia was correlated with morphologic
      parameters at this time point and used to calculate the dose-modifying factor
      (DMF) of glutamine and amifostine on acute small bowel radiation damage. RESULTS:
      After WBI, a time- and dose-dependent decrease in plasma citrulline level was
      observed with a significant dose-response relationship at 84 h. At this time
      point, citrullinemia significantly correlated with jejunal crypt regeneration (p
      < 0.001) and epithelial surface lining (p = 0.001). A DMF of 1.0 and 1.5 was
      computed at the effective dose 50 (ED50) level for glutamine and amifostine,
      respectively. CONCLUSIONS: Citrullinemia can be used to quantify acute small
      bowel epithelial radiation damage after single-dose WBI. Radiation-induced
      changes in citrullinemia are most pronounced at 3 1/2 to 4 days postirradiation.
      At this time point, citrullinemia correlates with morphologic endpoints for
      epithelial radiation damage.

PMID- 14575839
TI  - Cell cycle effect of gemcitabine and its role in the radiosensitizing mechanism
      in vitro.
AB  - PURPOSE: The mechanism of radiosensitization by gemcitabine is still unclear. It
      has been hypothesized that the accumulation of cells in early S phase may play a
      role in enhancing radiosensitivity. METHODS AND MATERIALS: The schedule
      dependency of the radiosensitizing effect was studied in ECV304, human bladder
      cancer cells, and H292, human lung cancer cells, by varying the incubation time
      and time interval between gemcitabine and radiation treatment. To determine the
      role of cell cycle perturbations in the radiosensitization, the influence of
      gemcitabine on the cell cycle at the moment of radiation was investigated by flow
      cytometry. RESULTS: The radiosensitizing effect increased with a longer
      incubation period: Dose enhancement factors varied from 1.30 to 2.82 in ECV304
      and from 1.04 to 1.78 in H292 after treatment during 8-32 h, respectively.
      Radiosensitization decreased with an increasing interval: Dose enhancement
      factors varied from 2.26 to 1.49 in ECV304 and from 1.45 to 1.11 in H292 after an
      interval 0-24 h, respectively. Cells were blocked in the early S phase of the
      cell cycle by gemcitabine. The highest percentage S-phase cells was observed
      after treatment with the schedules that resulted in the highest radiosensitizing
      effect. CONCLUSIONS: We observed a clear schedule-dependent radiosensitization by
      gemcitabine. Our findings demonstrated a correlation between gemcitabine-induced
      early S-phase block and the radiosensitizing effect.

PMID- 14575840
TI  - Experimental application of boron neutron capture therapy to undifferentiated
      thyroid carcinoma.
AB  - PURPOSE: Undifferentiated thyroid carcinoma (UTC) lacks an effective treatment.
      Boron neutron capture therapy (BNCT) is based on the nuclear reaction
      (10)B(n,alpha) (7)Li. These particles destroy the tumor locally due to their high
      linear energy transfer (LET). Mice transplanted with the human cell line of UTC
      ARO have a selective uptake of (10)B-borophenylalanine (BPA). The complete BNCT
      was performed to explore its possible application. METHODS AND MATERIALS: Mice
      were distributed into four groups: (1) no treatment; (2) neutron beam alone; (3)
      350 mg/kg body weight (b.w.) BPA plus irradiation; (4) 600 mg/kg b.w. BPA plus
      irradiation. Follow-up was performed by measurement of tumor volume, histologic
      analysis, and assessment of DNA damage using the comet assay. RESULTS: The tumor
      continued to grow in Groups 1 and 2. In Group 3, a slow-down of tumor growth was
      observed in all mice, and a complete stop was observed in 100% of mice of Group
      4. Complete disappearance of the tumor was observed in 50% of the mice that had
      an initial tumor volume of less than 50 mm(3) (Groups 3 and 4). DNA damage showed
      a progressive increase from Group 1 through 4. CONCLUSION: These data show, for
      the first time, that UTC is amenable to treatment by BNCT.

PMID- 14575841
TI  - Changes in oligodendrocytes and myelin gene expression after radiation in the
      rodent spinal cord.
AB  - PURPOSE: The aim of this study was to assess changes in oligodendrocytes (OL),
      myelin gene expression, and their relationships with late demyelination after
      irradiation. METHODS AND MATERIALS: Adult rats were given single doses of 8 or 22
      Gy to the cervical spinal cord. Immunohistochemistry for APC or GST-pi was used
      to identify OL. Changes in myelin gene expression were assessed using RT-PCR for
      proteolipid protein (PLP). Luxol fast blue staining was used to assess
      demyelination. CNP-(beta)geo transgenic mice were used to confirm some of the
      results of the rat model. Cells of the oligodendroglial lineage in these animals
      express beta-galactosidase (beta-gal). RESULTS: Early apoptosis of APC, GST-pi,
      and beta-galactosidase positive cells was observed in the spinal cord of rats and
      CNP-(beta)geo mice. At 24 h after 22 Gy, there was a significant decrease in OL
      density. Cell density continued to decline thereafter after both 8 and 22 Gy, and
      a reduction in PLP expression was observed at 4-5 weeks. A further decrease in
      PLP expression was seen beginning at 18 weeks after 22 Gy only. Demyelination was
      observed at 19 weeks after 22 Gy. CONCLUSIONS: Apoptosis of OL and changes in OL
      density and PLP gene expression were observed early after both 8 and 22 Gy. This
      suggests that these early changes are unlikely to be directly related to the late
      demyelination observed.

PMID- 14575842
TI  - The low alpha/beta ratio for prostate cancer: what does the clinical outcome of
      HDR brachytherapy tell us?
AB  - PURPOSE: Accumulating evidence demonstrates that prostate cancer has a low
      alpha/beta ratio. However, several challenging issues have been raised from
      previous studies, including the biologic equivalence between external beam
      radiotherapy (EBRT) and brachytherapy, the effect of relative biologic
      effectiveness (RBE) for permanent implantation, and the systematic uncertainties
      of multi-institutional and multi-modality clinical data. The purpose of this
      study is to address these issues by reexamining a reported clinical outcome of
      high-dose-rate (HDR) brachytherapy and to confirm the low alpha/beta ratio for
      prostate cancer. METHODS AND MATERIALS: The generalized linear-quadratic (LQ)
      model with considerations of sublethal damage repair and clonogen repopulation
      was used to calculate the cell-killing efficiency of radiotherapy treatments for
      prostate cancer. Standard models of tumor cure based on Poisson statistics were
      used to bridge cell killing to treatment outcome. The data collected in a
      clinical trial using EBRT plus HDR brachytherapy boost for prostate cancer at
      William Beaumont Hospital (WBH) were reanalyzed. A 4-year post-treatment time
      endpoint was chosen as compared to the 3-year endpoint used in the previous study
      because of better maturity and stability of the data. The least chi-square method
      was employed to fit the clinical data to estimate the LQ parameters as well as
      their confidence intervals. The number of clonogens for prostate tumors derived
      in a separate study was used as a constraint for the data modeling to improve the
      confidence level. RESULTS: Our analysis demonstrates that only relationships
      among the LQ parameters, not their definitive and unique values, can be derived
      from the WBH data set alone. This is due to the large statistical uncertainties,
      i.e., the small numbers of sampled patients. By combining with the results
      obtained with the clinical data from Memorial Sloan-Kettering Cancer Center
      (MSKCC), a new set of LQ parameters (alpha = 0.14 +/- 0.05 Gy(-1), alpha/beta =
      3.1(-1.6)(+2.6) Gy) was obtained from the current analysis of the WBH data
      without dealing with data from permanent implants. The results are consistent
      with a previous study based on the biologic equivalence between EBRT and
      permanent implants with a consideration of tumor repopulation. This set of LQ
      parameters provides a consistent interpretation of clinical data currently
      available for prostate cancer. CONCLUSIONS: This study provides further evidence
      to support that prostate cancer has a low alpha/beta ratio of about 3.1 Gy. This
      study shows that the RBE effect in permanent implantation may not be clinically
      significant for prostate cancer. The consistency found between this analysis and
      the previous reported study supports the general biologic equivalence between
      EBRT and brachytherapy treatments for prostate cancer. The low alpha/beta ratio
      opens the door to search for more effective radiotherapeutic approaches for
      prostate cancer, e.g., hypofractionation radiotherapy.

PMID- 14575843
TI  - Radiation-induced cognitive dysfunction: the protective effect of ethyol in young
      rats.
AB  - PURPOSE: To evaluate the protective learning and memory effect of Ethyol in
      irradiated young rats. METHODS AND MATERIALS: One hundred twenty-eight 45-day-old
      Wistar rats received whole brain fractionated radiation (30 Gy), whereas 48 rats
      received sham irradiation. Four irradiated subgroups were defined: saline, 37.5
      mg/kg, 75 mg/kg, and 150 mg/kg Ethyol. Sequential behavioral studies including
      one-way and two-way avoidance tasks were undertaken before and after radiation.
      RESULTS: Before radiation, the performances of all groups were similar. For the
      one-way avoidance task, at 1, 3, and 6 months postradiation, saline-irradiated
      rats had a lower percentage of avoidance than sham- or Ethyol- (75 or 150 mg/kg)
      irradiated rats (p <or= 0.001). Nevertheless, lower percentage of avoidance (p
      <or= 0.001) was only seen at 1 month postradiation in saline-irradiated rats,
      after comparison with their preradiation values. For the two-way avoidance task,
      performed only after radiation, saline-irradiated rats had a lower percentage of
      avoidance than sham- or Ethyol- (150 or 75 mg/kg) irradiated rats at 1, 2.5, 4.5,
      and 7.5 months (p = 0.000). Rats treated with Ethyol did not differ from sham
      irradiated rats in both avoidance tasks, except for the 37.5 mg/kg-Ethyol group
      which showed lower performances 6 months postradiation (p = 0.005, one-way
      avoidance). CONCLUSIONS: Treatment with 75 or 150 mg/kg of Ethyol prevents
      radiation-induced learning and transitory memory dysfunction in young rats.

PMID- 14575844
TI  - How low is the alpha/beta ratio for prostate cancer?
AB  - PURPOSE: Recently, low alpha/beta values of 1.2 and 1.5 Gy for prostate tumors
      have been derived from clinical results of external beam radiotherapy and of
      permanent implants of (125)I and (103)Pd. In the analyses the contributions of
      tumor repopulation, and edema as a result of inserting radioactive seeds in the
      prostate, have been ignored. In this paper we reanalyzed the clinical data and
      introduced the contribution of repopulation and edema. METHODS AND MATERIALS: The
      linear quadratic-biologically effective dose model was used for reanalysis. In
      this model, the influence of repopulation and edema has been taken into account.
      The biologically effective dose was calculated as a function of alpha/beta for 2
      brachytherapy regimens with (125)I and (103)Pd and 2 fractionated treatments, and
      for different half-times for repair of sublethal damage for the brachytherapy
      regimens. RESULTS: We have found a plausible alpha/beta value of 3.1 to 3.9 Gy,
      an alpha value of 0.1 to 0.15 Gy(-1), and a half-time of repair of about 0.5 h.
      CONCLUSIONS: It seems now that the alpha/beta value is low, 3.1-3.9 Gy, but not
      as low as the 1.2 and 1.5 Gy reported earlier.

PMID- 14575845
TI  - Can digitally reconstructed radiographs (DRRS) replace simulation films in
      prostate cancer conformal radiotherapy?
AB  - PURPOSE: To evaluate the precision of using digitally reconstructed radiographs
      (DRRs) of either 3 mm or 6 mm slice separation vs. using simulator images for the
      setup verification of patients receiving CT planned conformal radiotherapy to the
      prostate. To calculate the transfer error between CT and simulator. METHODS AND
      MATERIALS: Twenty patients were CT scanned (3 mm slice spacing/width). DRRs were
      generated for both 3 mm (DRR 3) and 6 mm (DRR 6) separations. DRRs and a
      simulator image of an anterior and a lateral field were used as reference images.
      Five observers matched each of the reference images to treatment images using the
      Theraview "Target check" facility. It was assumed that poorer images would lead
      to a loss of precision of field placement estimations (FPE) between observers.
      The study was designed to detect a difference greater than 1.5 mm(2) in the
      precision of image placement. The transfer error was the mean difference in the
      setup error derived from the DRRs and the simulation films. RESULTS: The
      precision of evaluations for simulator films and 3 mm DRRs were similar. There
      was a trend for the DRR 6 mm to achieve less precise results which was greatest
      for craniocaudal examinations (variance: simulator 1.5 mm(2), DRR6 2.8 mm(2), p =
      0.17), but this did not reach statistical significance. A range of transfer
      errors was identified, with standard deviations ranging from 1.7 to 4.2 mm. There
      was evidence of a significant systematic bias in anterior craniocaudal (1.3-1.9
      mm, p < 0.004) and anterior posterior (-1.9 mm, p = 0.027). CONCLUSION: The
      precision of setup evaluations using DRRs is similar to that achieved by using
      simulator fields when planning conformal prostate radiotherapy. The use of DRRs
      could reduce systematic errors introduced in the planning process.

PMID- 14575847
TI  - A simple and reliable index for scoring rival stereotactic radiosurgery plans.
AB  - PURPOSE: A simple and robust index for ranking rival stereotactic radiosurgery
      plans is presented. METHODS: The radiosurgery plan score index, CGI
      (Conformity/Gradient Index), is an average of a conformity score and a gradient
      score. Computation of the CGI score is simple, requiring only three pieces of
      data: (1) the total volume irradiated to the prescription isodose level, (2) the
      volume of the target, and (3) the total volume irradiated at half of the
      prescription isodose level. The overall CGI Index is a simple function of these
      three pieces of data. RESULTS: When multiple sets of rival stereotactic
      radiosurgery plans were ranked with respect to this single score index, the
      resulting plan rankings closely matched the plan rankings according to biologic
      indices (calculated nontarget brain normal tissue complication probabilities).
      CONCLUSIONS: The CGI is a simple and fast plan evaluation tool that can assist
      the radiosurgery planner in evaluating and optimizing multiple candidate
      radiosurgery plans.

PMID- 14575846
TI  - Technical aspects of daily online positioning of the prostate for three
      dimensional conformal radiotherapy using an electronic portal imaging device.
AB  - PURPOSE: To develop a real-time electronic portal imaging device (EPID) procedure
      to identify intraprostatic gold markers and correct daily variations in target
      position during external beam radiotherapy for prostate cancer. METHODS AND
      MATERIALS: Pretherapy electronic portal images (EPIs) were acquired with a small
      portion of the therapeutic 18-MV dose from an orthogonal pair of treatment
      fields. The position of the intraprostatic gold markers on the EPIs was aligned
      with that on the simulation digitally reconstructed radiographs. If the initial
      three-dimensional target displacement (3DI) exceeded 5 mm or rotations exceeded 3
      degrees, the beam was realigned before the remainder of the dose was delivered.
      Field-only EPIs were then acquired for all fields and offline analysis was
      performed to determine the final 3D target placement (3DF). RESULTS: Twenty
      patients completed protocol-specified treatment, and all markers were identified
      on 99.6% of the pretherapy EPIs. Overall, 53% of treatment fractions were
      realigned. The mean 3DI was 5.6 mm in all patients (range 3.7-9.3), and the mean
      3DF was 2.8 mm (range 1.6-4.0), which was statistically significant (p < 0.001).
      Rotational corrections were made on 15% of treatments. Mean treatment duration
      was 1.4 min greater for protocol patients than for similar patients in whom
      localization was not performed. CONCLUSIONS: Frequent field misalignment occurs
      when external fiducial marks are used for patient alignment. Misalignments can be
      readily and rapidly identified and corrected with an EPID-based online correction
      procedure that integrates commercially available equipment and software.

PMID- 14575848
TI  - Comparison of an image registration technique based on normalized mutual
      information with a standard method utilizing implanted markers in the staged
      radiosurgical treatment of large arteriovenous malformations.
AB  - PURPOSE: To compare a noninvasive technique based on normalized mutual
      information for registering image sets associated with staged radiosurgical
      treatments of large arteriovenous malformations (AVMs), with a gold-standard
      method using radiographically evident markers implanted in the skull. METHODS:
      Nine patients receiving multistage treatment of large AVMs at the University of
      California at San Francisco (UCSF) gamma knife facility were included in this
      study. For each patient, the transformations of shot coordinates between a
      reference treatment stage and subsequent treatment stages were determined at
      UCSF, based on radiographically defined coordinates of implanted markers in each
      stereotactic space. A magnetic resonance (MR) image set was acquired for each
      treatment stage, and used for treatment planning. The two MR image sets for each
      treatment pair were sent to Yale for an unbiased, independent analysis of shot
      transformations. An image registration technique based on normalized mutual
      information was used to produce a single fused image study for each treatment
      pair. External copper sulfate fiducial markers for both image sets were evident
      on the fused images, allowing coordinates in both stereotactic systems to be
      defined. Coordinate transformation between the two systems was determined, based
      on digitized coordinates of seven common fiducial marker images. RESULTS: The
      average measured overall root-mean-square discrepancy between the Yale and UCSF
      transformed shot coordinates is 1.1 +/- 0.3 mm. The corresponding error in Yale
      transformed coordinates is 1.0 +/- 0.3 mm, assuming an inherent 0.5 mm error in
      the UCSF method. CONCLUSIONS: The normalized mutual information method can be
      used to obtain good image registration between successive sessions in staged
      treatments. Further improvements in the reported methodology are outlined.
      Because the mutual information method is less invasive than the implanted marker
      method, it may be preferable in many cases.

PMID- 14575849
TI  - Quality assurance of magnetic resonance spectroscopic imaging-derived metabolic
      data.
AB  - PURPOSE: Spatially resolved metabolite maps, as measured by magnetic resonance
      spectroscopic imaging (MRSI) methods, are being increasingly used to acquire
      metabolic information to guide therapy, with metabolite ratio maps perhaps
      providing the most diagnostic information. We present a quality assurance
      procedure for MRSI-derived metabolic data acquired ultimately for guiding
      conformal radiotherapy. METHODS AND MATERIALS: An MRSI phantom filled with brain
      mimicking solutions was custom-built with an insert holding eight vials
      containing calibration solutions of precisely varying metabolite concentrations
      that emulated increasing grade/density of brain tumor. Phantom metabolite ratios
      calculated from fully relaxed 1D, 2D, and 3D MRS data for each vial were compared
      with calibrated metabolite ratios acquired at 9.4 T. Additionally, 3D ratio maps
      were "discretized" to eight pseudoabnormality levels on a slice-by-slice basis
      and the accuracy of this procedure was verified. RESULTS: Regression analysis
      revealed expected linear relationships between experimental and calibration
      metabolite ratios with intercepts close to zero for the three acquisition modes.
      1D MRS data agreed most with theoretical considerations (regression coefficient,
      b = 0.969; intercept 0.008). The 2D (b = 1.049; intercept -0.199) and 3D
      (correlation coefficient r(2) = 0.9978-0.7336 for five slices) MRSI indicated
      reduced MRS data quality in regions of degraded B(0) and B(1) homogeneity.
      Pseudoabnormality levels were found to be consistent with expectations within
      regions of adequate B(0) homogeneity. CONCLUSIONS: This simple phantom-based
      approach to generate baseline calibration curves for all MRS acquisition modes
      may be useful to identify temporal deviations from acceptable data quality in a
      routine clinical environment or for testing new MRS and MRSI acquisition
      software.

PMID- 14575850
TI  - Measurement of the ultrasound backscatter signal from three seed types as a
      function of incidence angle: application to permanent prostate brachytherapy.
AB  - PURPOSE: To measure the relative ultrasound backscatter of different seed types
      as a function of seed orientation and to evaluate the corresponding images of
      these seeds. METHODS AND MATERIALS: Three seed types were evaluated: OncoSeed
      (standard), EchoSeed (corrugated), and RAPID Strand(RS). Ultrasound images for
      angles of incidence varying from 90 degrees (perpendicular) to 20 degrees at 5MHz
      and 7.5MHz were produced by raster scanning the seeds in a degassed water bath.
      Seed images were visually inspected and analyzed using the integrated-optical
      density (IOD) method. RESULTS: Corrugated seeds appear as contiguous objects over
      the range of frequencies and orientations examined, whereas standard seeds appear
      as contiguous objects from 90 degrees to 80 degrees only. The ranges and means of
      the backscattered IOD ratio of the seeds from 85 degrees to 20 degrees were:
      (corrugated vs. standard) 1.48 to 3.72 (2.32 +/- 0.62) for 5 MHz and 1.26 to 3.77
      (2.19 +/- 0.84) for 7.5 MHz and (corrugated vs. RS) 1.21 to 9.53 (2.98 +/- 2.48)
      for 5 MHz and 1.008 to 10.86 (2.79 +/- 3.08) for 7.5 MHz. Backscattered signal
      increase ranged from 1.66 dB to 20.7 dB for the corrugated seed as compared to
      the other seeds. CONCLUSIONS: Corrugated seeds produce greater backscatter signal
      and a more readily identifiable seed image over a large range of seed orientation
      as compared with standard brachytherapy seeds.

PMID- 14575851
TI  - In vivo thermoluminescence dosimetry dose verification of transperineal 192Ir
      high-dose-rate brachytherapy using CT-based planning for the treatment of
      prostate cancer.
AB  - PURPOSE: To evaluate the potential of in vivo thermoluminescence dosimetry to
      estimate the accuracy of dose delivery in conformal high-dose-rate brachytherapy
      of prostate cancer. METHODS AND MATERIALS: A total of 50 LiF, TLD-100 cylindrical
      rods were calibrated in the dose range of interest and used as a batch for all
      fractions. Fourteen dosimeters for every treatment fraction were loaded in a
      plastic 4F catheter that was fixed in either one of the 6F needles implanted for
      treatment purposes or in an extra needle implanted after consulting with the
      patient. The 6F needles were placed either close to the urethra or in the
      vicinity of the median posterior wall of the prostate. Initial results are
      presented for 18 treatment fractions in 5 patients and compared to corresponding
      data calculated using the commercial treatment planning system used for the
      planning of the treatments based on CT images acquired postimplantation. RESULTS:
      The maximum observed mean difference between planned and delivered dose within a
      single treatment fraction was 8.57% +/- 2.61% (root mean square [RMS] errors from
      4.03% to 9.73%). Corresponding values obtained after averaging results over all
      fractions of a patient were 6.88% +/- 4.93% (RMS errors from 4.82% to 7.32%).
      Experimental results of each fraction corresponding to the same patient point
      were found to agree within experimental uncertainties. CONCLUSIONS: Experimental
      results indicate that the proposed method is feasible for dose verification
      purposes and suggest that dose delivery in transperineal high-dose-rate
      brachytherapy after CT-based planning can be of acceptable accuracy.

PMID- 14575852
TI  - Modification of Gill-Thomas-Cosman frame for extracranial head-and-neck
      stereotactic radiotherapy.
AB  - PURPOSE: A modification of a commercially available, noninvasive, relocatable,
      stereotactic Gill-Thomas-Cosman (GTC) head frame is presented for treatment of
      extracranial lesions of the head and neck, base of the skull, and inferior
      nasopharyngeal region. METHODS AND MATERIALS: Skull-based and nasopharyngeal
      lesions cannot be treated with the GTC frame because it obstructs the beam path.
      To treat those lesions, the GTC frame was modified without compromising the
      integrity, flexibility, or use of the treatment software. The modification uses a
      set of aluminum extension rods of variable lengths and bevels to support a
      modified dental plate. The extension rods allow the dental tray and attached GTC
      frame to be lowered so that the more inferior regions may be treated. Ten
      patients underwent CT with the modified frame and CT localizer. For some
      patients, MRI was acquired without the frame. Image fusion of MRI and CT scans
      was used to delineate the target volume, and planning was done with the existing
      software for proper treatment. RESULTS: The modification of the GTC frame has
      been successful in imaging, planning, and extending the treatment domain for the
      base of the skull, nasopharyngeal regions, and other superior lesions of the head
      and neck. The reproducibility of the modified frame and the patient localization
      helmet technique was identical to that of the unmodified frame. CONCLUSION: The
      modification of the GTC frame is simple and accurate. It provides flexibility in
      treating an extended range of the base of the skull, nasopharyngeal region, and
      other superior lesions of the head and neck that otherwise could not be treated
      with the GTC frame.

PMID- 14575853
TI  - In regard to DAI et al.: inhibition of hypoxia inducible factor 1alpha causes
      oxygen-independent cytotoxicity and induces p53 independent apoptosis in
      glioblastoma cells. IJROBP 2003;55:1027-1036).

PMID- 14575854
TI  - Evidence-based medicine or fuzzy-math!

PMID- 14575856
TI  - Complementary and alternative medicine in radiotherapy patients--more harm than
      expected? In regard to D'Amico et al.: self-administration of untested medical
      therapy for treatment of prostate cancer can lead to clinically significant
      adverse events. IJROBP 2002;54:1311-1313.

PMID- 14575858
TI  - In regard to Ghaly et al., IJROBP 2003;55:1288-1293.

PMID- 14575860
TI  - In regard to Marijnen et al.: does radiotherapy compensate for a positive
      resection margin in rectal cancer patients? IJROBP 2003;55:1311-1320.

PMID- 14575862
TI  - The polybasic region of Ras and Rho family small GTPases: a regulator of protein
      interactions and membrane association and a site of nuclear localization signal
      sequences.
AB  - Many small GTPases in the Ras and Rho families have a C-terminal polybasic region
      (PBR) comprised of multiple lysines or arginines. The PBR controls diverse
      functions of these small GTPases, including their ability to associate with
      membranes, interact with specific proteins, and localize in subcellular
      compartments. Different signaling pathways mediated by Ras and Rho family members
      may converge when the small GTPases are directed by their PBRs to shared binding
      sites in specific proteins or at cell membranes. The PBR promotes the
      interactions of small GTPases with SmgGDS, which is a nucleocytoplasmic shuttling
      protein that stimulates guanine nucleotide exchange by small GTPases. The PBR of
      Rac1 was recently found to have a functional nuclear localization signal (NLS)
      sequence, which enhances the nuclear accumulation of protein complexes containing
      SmgGDS and Rac1. Sequence analysis demonstrates that canonical NLS sequences (K
      K/R-x-K/R) are present in the PBRs of additional Ras and Rho family members, and
      are evolutionarily conserved across several phyla. These findings suggest that
      the PBR regulates the nucleocytoplasmic shuttling of some Ras and Rho family
      members when they are in protein complexes that are too large to diffuse through
      nuclear pores. These diverse functions of the PBR indicate its critical role in
      signaling by Ras and Rho family GTPases.

PMID- 14575863
TI  - The class III adenylyl cyclases: multi-purpose signalling modules.
AB  - cAMP serves as a second messenger in virtually all organisms. The most wide
      spread class of cAMP-generating enzymes are the class III adenylyl cyclases. Most
      class III adenylyl cyclases are multi-domain proteins. The catalytic domains
      exclusively work as dimers, catalysis proceeds at the dimer interface, so that
      both monomers provide catalytic residues to each catalytic center. Inspection of
      amino acid sequence profiles suggests a division of the class III adenylyl
      cyclases in to four subclasses, class IIIa-IIId. Genome projects and postgenomic
      analysis have provided novel aspects in terms of catalysis and regulation.
      Alterations in the canonical catalytic residues occur in all four subclasses
      suggesting a plasticity of the catalytic mechanisms. The vast variety of
      additional, probably regulatory modules found in class III adenylyl cyclases
      obviously reflects a large collection of regulatory inputs the catalytic domains
      have adapted to. The large versatility of class III adenylyl cyclase catalytic
      domains remains a major scientific challenge.

PMID- 14575864
TI  - IGF-I stimulates IL-8 production in the promyelocytic cell line HL-60 through
      activation of extracellular signal-regulated protein kinase.
AB  - Interleukin (IL)-8 serves as a major chemoattractant for neutrophils and has also
      been proposed to affect cancer progression. In the present study, we show that
      IGF-I stimulates IL-8 mRNA expression and IL-8 secretion in the leukemic cell
      line HL-60. Stimulation of IL-8 expression was completely attenuated by two
      inhibitors of mitogen-activated protein kinase (MAPK) kinase (MEK), which
      phosphorylates the MAPKs extracellular-regulated kinase (ERK)1 and ERK2, and by
      the c-Jun NH2-terminal kinase (JNK) inhibitor SP600125. In contrast, inhibitors
      of p38 MAPK and phosphatidylinositol-3 kinase (PI3K) did not abrogate the effect
      of IGF-I. We also show that IGF-I stimulates the activation of ERK1 and ERK2, but
      we could not detect any effect of IGF-I on the phosphorylation of p38, JNK(p46)
      or JNK(p54). Collectively, our results suggest that basal JNK activity and
      activation of the MEK-ERK pathway are required for upregulation of IL-8 by IGF-I
      in HL-60 cells.

PMID- 14575865
TI  - Cell surface receptors activate p21-activated kinase 1 via multiple Ras and PI3
      kinase-dependent pathways.
AB  - p21-activated kinases (PAKs) were the first identified mammalian members of a
      growing family of Ste20-like serine-threonine protein kinases. In this study, we
      show that PAK1 can be stimulated by carbachol, lysophosphatidic acid (LPA),
      epidermal growth factor (EGF), and phorbol 12-myristate 13-acetate (PMA) by
      multiple independent and overlapping pathways. Dominant-negative Ras, Rac, and
      Cdc42 inhibited PAK1 activation by all of these agonists, while active Rac1 and
      Cdc42 were sufficient to maximally activate PAK1 in the absence of any treatment.
      Active Ras induced only a weak activation of PAK1 that could be potentiated by
      muscarinic receptor stimulation. Studies using inhibitors of the EGF receptor
      tyrosine kinase, phosphatidylinositol 3-kinase (PI3-kinase) and protein kinase C
      (PKC) revealed that all of the cell surface agonists could activate PAK1 through
      pathways independent of PKC, that EGF stimulated a PI3-kinase dependent pathway
      to stimulate PAK1, and that muscarinic receptor stimulation of PAK1 was
      predominantly mediated through this EGF-R-dependent mechanism. Activation of PAK1
      by LPA was independent of PI3-kinase and the EGF receptor, but was inhibited by
      dominant-negative RhoA. These results identify multiple Ras-dependent pathways to
      activation of PAK1.

PMID- 14575866
TI  - Sensitization of adenylate cyclase by short-term activation of 5-HT1A receptors.
AB  - Long-term (18 h) activation of 5-HT1A receptors alters 5-HT1A receptor-G protein
      coupling and leads to heterologous sensitization of adenylate cyclase. In
      contrast, the effects of short-term (2 h) 5-HT1A receptor activation on
      subsequent adenylate cyclase activity have not been determined. The present study
      examined and characterized 5-HT1A receptor-induced heterologous sensitization
      following short-term activation in CHO-5-HT1A cells. Short-term activation of 5
      HT1A receptors with full agonists, as well as the partial agonist, buspirone,
      markedly enhanced subsequent forskolin-stimulated cyclic AMP accumulation. This
      heterologous sensitization was evident after 30 min treatment with 5HT and
      appeared to be near maximal following 2 h agonist treatment. Sensitization was
      characterized by a dose-dependent increase in forskolin-stimulated cyclic AMP
      accumulation and was prevented by WAY 100635 or by pertussis toxin treatment. The
      ability of the 5-HT1A agonists to induce heterologous sensitization was not
      significantly altered by agents shown previously to modulate 5-HT1A-mediated
      inhibition of cyclic AMP accumulation.

PMID- 14575867
TI  - Phosphoinositide 3-kinase is involved in Xenopus and Labrus melanophore
      aggregation.
AB  - Melanophores are pigmented cells capable of quick colour changes through
      coordinated transport of their intracellular pigment granules. We demonstrate the
      involvement of phosphoinositide 3-kinase (PI3-K) in Xenopus and Labrus
      aggregation by the use of the PI3-K inhibitor, LY-294002. In Xenopus, wortmannin
      insensitive PI3-K was found to be essential for the aggregation, mitogen
      activated protein kinase (MAPK) activation and tyrosine phosphorylation of a 280
      kDa protein, and for the maintenance of low cyclic adenosine 3':5'-monophosphate
      (cAMP) during the aggregated state. Pre-aggregated cells disperse completely to
      LY-294002 at 50-100 muM, involving a transient elevation in cAMP due to adenylate
      cyclase (AC) stimulation or to inhibition of cyclic nucleotide phosphodiesterase
      (PDE). The inactive analogue LY-303511 did not induce dispersion at the same
      concentrations. PDE4 and/or PDE2 was found to be involved in melanosome
      aggregation. The similar kinetics of LY-294002 and various PDE inhibitors
      indicates that the elevation of cAMP might be due to inhibition of PDE. In Labrus
      melanophores, LY-294002 had a less dramatic effect, probably due to less
      dependence on PDE in regulation of cAMP levels. In Xenopus aggregation, we
      suggest that melatonin stimulation of the Mel1c receptor via G(beta gamma)
      activates PI3-K that, directly or indirectly via MAPK, activates PDE.

PMID- 14575868
TI  - Activation of P2X7 purinoceptor-stimulated TGF-beta 1 mRNA expression involves
      PKC/MAPK signalling pathway in a rat brain-derived type-2 astrocyte cell line,
      RBA-2.
AB  - The present study investigates the receptor and mechanisms involved in ATP
      stimulated transforming growth factor-beta 1 (TGF-beta 1) mRNA expression of a
      type-2 astrocyte cell line, RBA-2. RT-PCR analysis revealed that RBA-2 type-2
      astrocytes possess abundant P2X(4) and P2X(7) receptors. ATP and P2X(7) receptor
      sensitive agonist, BzATP, both stimulated TGF-beta 1 mRNA expression in a time
      and dose-dependent manner. The stimulation required a minimum of 500 muM ATP;
      BzATP was much more potent that ATP, and P2X(7)-selective antagonist, oATP,
      inhibited the effects. In addition, ATP metabolites ADP, AMP and adenosine were
      ineffective in stimulation of TGF-beta 1 mRNA expression. Thus, the effect of ATP
      was mediated through the P2X(7) receptors. To investigate further the mechanisms
      by which the P2X(7) receptor mediated the TGF-beta 1 mRNA expression, the cells
      were treated with inhibitors for mitogen-activated kinase (MAPK) or protein
      kinase C (PKC), PD98059 or GF109203X, respectively. Both PD98059 and GF109203X
      inhibited the ATP-stimulated TGF-beta 1 mRNA expression. Furthermore, ATP and
      BzATP stimulated ERK1/2 activation and the activation was inhibited by PKC
      inhibitors, GF109203X and Go6976. In conclusion, activation of P2X(7) receptors
      enhanced TGF-beta 1 mRNA expression and the effect involved PKC/MAPK signalling
      pathway in RBA-2 type-2 astrocytes.

PMID- 14575869
TI  - 1,10-Phenanthroline phosphorylates (activates) MAP kinase in Xenopus oocytes.
AB  - The membrane-permeable intracellular heavy metal chelator, 1,10-phenanthroline,
      which prevents progesterone-induced germinal vesicle breakdown (GVBD), would be
      expected to regulate phosphorylation (activation) of the MAP kinase (MAPK)
      cascade in Xenopus oocytes. Here, our experiments show that 1,10-phenanthroline
      itself results in the phosphorylation of MAPK in both oocytes and a cell-free
      system. In contrast, 1,7-phenanthroline, the nonchelating analogue, had no
      effect. A supplement of zinc (as a heavy metal) given to 1,10-phenanthroline
      loaded oocytes suppressed the stimulatory effects of 1,10-phenanthroline, while
      1,10-phenanthroline withdrawal caused dephosphorylation of activated MAPK.
      Further, treatment with a MEK (a MAPK kinase) inhibitor, PD 098059 or U0126,
      suppressed 1,10-phenanthroline-stimulated MAPK phosphorylation, indicating that
      1,10-phenanthroline can phosphorylate MAPK in a MEK-dependent fashion. Our
      results suggest that phosphorylation of MAPK by 1,10-phenanthroline depends on
      the interaction of MEK. Thus, the intracellular heavy metal (zinc) regulates MAPK
      phosphorylation and 1,10-phenanthroline can serve as a unique tool for
      investigating MAPK phosphorylation mechanism.

PMID- 14575871
TI  - Fear-conditioned suppression of REM sleep: relationship to Fos expression
      patterns in limbic and brainstem regions in BALB/cJ mice.
AB  - In fear conditioning, shock training (ST) and shock-associated fearful cues (FC)
      produce relatively selective decreases in rapid eye movement sleep (REM) in mice
      that vary with strain, and can last for an extended period. We examined sleep in
      BALB/cJ mice over 6 h after ST and FC, and in handling and tone control
      conditions. In separate groups of mice, we used immunohistochemical techniques to
      examine Fos expression in limbic and brainstem regions involved in fear
      conditioning and in the regulation of REM in 2-h intervals over this period.
      Significant reductions in REM were observed at 2 and 4 h after ST. Fos expression
      in the brainstem was significantly elevated at 2 h after ST in the laterodorsal
      and peduculopontine tegmentum, up to 4 h in the dorsal raphe nucleus (DRN) and up
      to 6 h in the locus coeruleus (LC). Significant elevations in Fos expression were
      observed in several regions of the amygdala up to 4 and 6 h after ST. Decreases
      in REM after FC were significant at 2 h. Increased Fos expression was observed in
      LC at 2 h and in DRN up to 6 h after FC. Increased Fos expression in the amygdala
      was observed in several regions of the amygdala at 2 h after FC, but not longer.
      Significant changes in Fos expression in the central nucleus of the amygdala were
      not observed at any time point examined or in any condition. The data are
      discussed with respect to the putative role of brainstem nuclei in regulating REM
      and the role of the amygdala in conditioned fear.

PMID- 14575870
TI  - Tyrosine phosphatase PTP1B modulates store-operated calcium influx.
AB  - We have studied modulation of "store-operated calcium influx" by tyrosine
      phosphatases in the pancreatic acinar cell line AR42J and in HEK 293 cells. We
      show that inhibition of tyrosine phosphatases by bis-(N,N-dimethyl-hydroxamido)
      hydrooxovanadate (DMHV) leads to an increase in Ca(2+) release-activated Ca(2+)
      (CRAC) entry. This effect can be blocked in the presence of 2-aminoethyldiphenyl
      borate (2-APB). Furthermore, transfection of HEK 293 cells with the human wild
      type tyrosine phosphatase PTP1B leads to inhibition of CRAC influx, whereas
      transfection with the substrate-trapping mutant of PTP1B (D181A) slightly
      increases Ca(2+) influx. It also decreases enzymatic activity of PTP1B as
      compared to non-transfected cells. Our data suggest that CRAC influx is modulated
      by tyrosine phosphorylation and dephosphorylation which involves the tyrosine
      phosphatase PTP1B.

PMID- 14575872
TI  - Similarities of SP-, NKA- and NKB-induced currents in rat dorsal root ganglion
      neurons.
AB  - Tachykinin (TK; including substance P (SP), neurokinin A (NKA) and neurokinin B
      (NKB))-induced currents (I(TK)s) were studied in freshly isolated rat dorsal root
      ganglion (DRG) neurons using whole-cell patch clamp recording and repatch
      techniques. All the three I(TK)s manifested features of fast activating kinetics,
      such as short latency and fast tau(on) and tau(off), and very slow
      desensitization. The concentration-response relationships for TKs show: (1).
      compared with the concentration-response curve for NKA, the curve for NKB shifted
      upwards, while that for SP shifted downwards; (2). the EC(50) values for NKB-,
      NKA- and SP-activated currents were very close to each other. The I-V curves for
      the three TKs were basically linear and arrayed in the order of NKB>NKA>SP; the
      reversal potentials for the three I(TK)s were all around +15 mV. Replacement of
      NaCl in the external solution by equimolar N-methyl-D-glucamine (NMDG) attenuated
      both NKA- and NKB-activated currents markedly, as it was the case with SP
      activated current caused by the opening of Na(+) preferring non-selective cation
      channels observed in our previous work. All the three TKs proved to inhibit
      coexistent GABA(A) receptor-mediated current (I(GABA)); this effect was removed
      by intracellular dialysis of GDP-beta-S or H-7. However, these drugs did not
      block the SP-, NKA- and NKB-activated currents at all, which indicated that
      I(TK)s were G-protein independent. In short, the responses of rat DRG neurons to
      SP, NKA and NKB were similar in essence, although the amplitudes of currents
      induced by the same concentration of the three TKs were different. Taking the
      results of this study and our previous studies together, we hypothesized that SP,
      NKA and NKB may induce inward currents through undiscovered channels that are
      associated with tachykinins receptors (NK1R, NK2R, NK3R, which have already been
      cloned), but independent of G-protein coupling and remains to be further
      investigated.

PMID- 14575873
TI  - Intraperitoneal injection of ghrelin induces Fos expression in the
      paraventricular nucleus of the hypothalamus in rats.
AB  - Ghrelin is a 28-amino acid peptide hormone secreted from the stomach that acts as
      a gut-brain peptide with potent stimulatory effects on food intake. The aim of
      the present study was to investigate the effects of peripheral ghrelin (1 and 10
      nmol/rat) injected intraperitoneally (i.p.) on food intake and neuronal activity
      in the hypothalamus and brain stem, as assessed by c-Fos-like-immunoreactivity (c
      FLI), using a confocal laser scanning microscope (cLSM) as a sensitive
      microscopic technique to detect c-FLI-positive neurons. Cumulative food intake
      was significantly increased 5.3- and 3.7-fold for the 4-h period after i.p.
      injection of ghrelin at both doses. The number of c-FLI-positive neurons in the
      paraventricular nucleus of the hypothalamus (PVN) was significantly increased
      after peripheral administration of ghrelin (1 nmol i.p.; median: 41.8) compared
      with i.p. saline (median: 17.5). As described before, c-fos expression was
      increased in the arcuate nucleus of the hypothalamus (ARC). In the nucleus of the
      solitary tract (NTS) or the area postrema (AP), there was no significant change
      in the density of c-FLI-positive neurons. Our data suggest that an activation of
      the arcuate-paraventricular axis may be part of the brain circuits involved in
      the orexigenic effect of peripheral ghrelin.

PMID- 14575874
TI  - Neuroprotective effects of insulin-like growth factor-I (IGF-I) following a
      penetrating brain injury in rats.
AB  - The elucidation of the molecular mechanisms involved in the response of brain
      tissue to trauma and the recognition of substances with neuroprotective
      properties is a prerequisite for the development of rational therapeutic
      approaches. In this study, we used a model of, unilateral, penetrating stab-like
      brain injury and examined the possible beneficial effects of post-injury
      administration of insulin-like growth factor-I (IGF-I) both at the cellular
      level, 4 and 12 h post-injury, and on the physical condition of the animals up to
      1 week following the trauma. The consequences of injury were assessed by
      immunohistochemically observing the expression of heat-shock protein 70 (Hsp70),
      which is thought to be a marker of cell stress and injury, and by staining the
      tissue with the TUNEL reaction, in order to detect apoptotic cell death. Injury
      resulted in an increase in the number of Hsp70 and TUNEL positive cells in the
      peritraumatic area. The physical condition of the rats was followed by measuring
      body weight changes, food and water intake and by estimating their "motor
      activity". IGF-I administration resulted in a significant decrease in the number
      of Hsp70 and TUNEL positive cells in the peritraumatic area. Additionally, it
      improved the total "motor activity" of injured rats, increased food intake and
      attenuated the post-injury body weight loss. IGF-I thus emerges as a factor
      acting both at the cellular level as a neuroprotectant and at the systemic level
      as an anabolic agent.

PMID- 14575875
TI  - Cell death and long-term maintenance of neuron-like state after differentiation
      of rat bone marrow stromal cells: a comparison of protocols.
AB  - Recent literature suggests that bone marrow stromal cells (BMSCs) may be
      differentiated into neuron-like and/or glia-like cells, implying that
      differentiated BMSCs may have potential use in cell replacement therapy for
      central nervous system disorders. However, many questions remain concerning the
      nature of BMSCs differentiated to express CNS antigens. For example, how long
      after differentiation do cells express CNS markers, and do differentiation
      procedures alter cell viability? This study compared neuronal differentiation
      methods in sister cell preparations, evaluating cell death and maintenance of the
      CNS antigen positivity after the Deng or Woodbury methods. Rat BMSCs were
      harvested, passaged, differentiated, placed in growth or maintenance media, and
      processed for cell viability or immunocytochemistry for NeuN and GFAP post
      differentiation. We report that the Woodbury differentiation protocol produced
      maximally 51% neuron-like cells, yet also produced significant cell death. The
      Deng differentiation method produced 13% neuron-like cells and without marked
      cell death. No significant increases in GFAP immunoreactivity (IR) were seen
      after differentiation by either protocol. Following both protocols, removal of
      cells from the maintenance media significantly decreased expression of NeuN.
      Thus, differentiation procedures may be substantially affected BMSC potential,
      and maintenance of immunoreactivity to neuronal antigens was dependent on
      specific, nonphysiological environmental conditions.

PMID- 14575876
TI  - N-acetylaspartylglutamate and beta-NAAG protect against injury induced by NMDA
      and hypoxia in primary spinal cord cultures.
AB  - The acidic dipeptide N-acetylaspartylglutamate (NAAG) is the most prevalent
      peptide in the central nervous system. NAAG is a low potency agonist at the NMDA
      receptor, and hydrolysis of NAAG yields the more potent excitatory amino acid
      neurotransmitter glutamate. beta-NAAG is a competitive inhibitor of the NAAG
      hydrolyzing enzyme N-acetylated alpha-linked acidic dipeptidase (NAAG peptidase
      activity) or glutamate carboxypeptidase II, and may also act as a NAAG-mimetic at
      some of the sites of NAAG pharmacological activity. Since NAAG has been shown to
      have neuroprotective characteristics in a number of experimental preparations, it
      is the purpose of the present study to specifically evaluate the possible
      efficacy of NAAG and beta-NAAG against NMDA- and hypoxia-induced injury to spinal
      cord mixed neuronal and glial cell cultures. NAAG (500-1000 microM) protected
      against NMDA- or hypoxia-induced injuries to spinal cord cultures, and the
      nonhydrolyzable analog beta-NAAG (250-1000 microM) completely eliminated the loss
      of viability caused by either insult. Both peptides also attenuated NMDA-induced
      increases in intraneuronal Ca(2+). Nonspecific mGluR antagonists, pertussis
      toxin, a stable cAMP analog, and manipulation of NAAG peptidase activity did not
      by themselves alter cell damage and did not influence the neuroprotective effects
      of NAAG. NAAG was not protective against kainate- or AMPA-induced cellular
      injury, while beta-NAAG was partially neuroprotective against both insults. At 2
      mM, NAAG and beta-NAAG reduced neuronal survival and increased intraneuronal
      Ca(2+); these effects were only marginally attenuated by dizocilpine and APV. The
      results indicate that NAAG and beta-NAAG protect against excitotoxic and hypoxic
      injury to spinal cord neurons, and do so predominantly by interactions with NMDA
      and not mGluR receptors.

PMID- 14575877
TI  - The effects of pitch tilt on postrotatory nystagmus in cats.
AB  - When the head is tilted away from the upright position immediately after
      termination of earth-vertical axis (EVA) head rotation at a constant velocity,
      the rotation axis of postrotatory nystagmus (PRN) is gradually directed toward
      gravity (spatial reorientation). During roll tilt, the extent of the axis shift
      varies among species. In cats, the reorientation is limited to about 30-45
      degrees of head tilt. In the present study, we examined features of PRN during
      pitch tilt in cats. The animals were rotated about EVA at a constant velocity of
      100 degrees /s for 120 s. Within 2 s after stopping EVA rotation, the animals
      were tilted toward the pitch plane by as much as +/-90 degrees (nose-down or nose
      up) in steps of 15 degrees. Eye movements were measured with 3D magnetic search
      coils. The angle of the PRN plane and its slow phase eye velocity (SPV) were
      measured. The duration of PRN decreased as pitch tilt increased regardless of
      whether the direction was nose-up or nose-down. The mean time constant of SPV was
      significantly longer for nose-up than for nose-down. PRN maintained its
      horizontal orientation without any vertical drift during pitch tilt, but there
      was little reorientation toward gravity. That is, no significant torsional
      component of SPV emerged to reorient the eyes according to gravity. Our results
      indicate that spatial reorientation depends on head orientation. For the PRN
      responses after pitch tilts in cats, the interactions of semicircular canal and
      otolith inputs in the central vestibular system might be vestigial.

PMID- 14575878
TI  - Combinatorial mutations in loops D and F strongly influence responses of the
      alpha7 nicotinic acetylcholine receptor to imidacloprid.
AB  - The nitro group of a neonicotinoid, imidacloprid, plays a key role in its
      selective actions on insect nicotinic acetylcholine receptors (nicotinic AChRs)
      and is postulated to bind close to residues Q79 in loop D and G189 in loop F of
      the chicken alpha7 nicotinic AChR. To evaluate the relative contributions of
      these residues to interactions with imidacloprid, Q79 and G189 were replaced in
      tandem by first basic then acidic residues. Changes in the currents evoked by
      imidacloprid and acetylcholine (ACh) on the alpha7 wild type and mutant receptors
      expressed in Xenopus laevis oocytes were investigated using two-electrode voltage
      clamp electrophysiology. An increase in the efficacy of imidacloprid for the
      alpha7 receptor resulting from the Q79K and Q79R mutations was suppressed by a
      G189E mutation in loop F. However, the increases in efficacy resulting from such
      Q79 mutations were scarcely influenced by a G189D substitution. Three-dimensional
      modeling of the alpha7 nicotinic AChR, based on the acetylcholine-binding protein
      (AChBP) of Lymnaea stagnalis, suggests that the reduced efficacy of imidacloprid
      following the G189E mutation is likely to result from carboxylate interference
      with the electronic interactions between the nitro group of imidacloprid and the
      basic residues in loop D.

PMID- 14575879
TI  - Glutamate release in the rat medial vestibular nucleus following unilateral
      labyrinthectomy using in vivo microdialysis.
AB  - We investigated the changes in glutamate release from the ipsi- and contra
      lesional medial vestibular nucleus (MVN) following unilateral labyrinthectomy
      (UL) by in vivo microdialysis study. The concentration of glutamate in the ipsi
      lesional MVN was decreased until 4 h. Twelve hours after UL, the concentration of
      glutamate was restored back to the basal level, after which the release did not
      show any change between 24 and 48 h post-UL. In contrast, the concentration of
      glutamate in the contra-lesional MVN, which increased immediately after UL,
      decreased gradually to the basal level until 3-4 h post-UL, followed by no
      further change. The difference in the glutamate concentration between ipsi- and
      contra-lesional MVN increased immediately after UL and gradually decreased
      accompanied by a reduction in the frequency of nystagmus, although spontaneous
      nystagmus had not disappeared by the time the imbalance of glutamate release
      diminished. These results suggest that the imbalance of glutamate release between
      bilateral nuclei induced the nystagmus, and the change in release is concerned
      with the rapid development of vestibular compensation.

PMID- 14575880
TI  - Cardioacceleratory responses to hypocretin-1 injections into rostral ventromedial
      medulla.
AB  - Intracisternal injections of hypocretin-1 (hcrt-1) have been shown to elicit
      sympathoexciatory responses. However, the location of central sites that may
      mediate these cardiovascular effects have not been clearly elucidated. This study
      was done in male Wistar rats to investigate the effects of microinjections of
      hcrt-1 into the rostral ventromedial medulla (RVMM) on mean arterial pressure
      (MAP), heart rate (HR) and the arterial baroreflex. An initial series of
      experiments was done to provide a detailed mapping of the location of hcrt-1- and
      hcrt-1 receptors (hcrtR-1)-like immunoreactivity (i.r.) in the RVMM region. Hcrt
      1 and hcrtR-1 ir were found throughout the RVMM region, but primarily within the
      magnocellular reticular nucleus and the adjacent nucleus paragigantocellularis
      lateralis. In the second series, this region containing hcrt-1 and hcrtR-1 ir was
      explored for sites that elicited changes in MAP and HR in the anaesthetized rat.
      Microinjection of hcrt-1 (0.5-2.5 pmol) into the region of magnocellular
      reticular nucleus elicited a dose-dependent increase in HR, with little or no
      change in MAP. Administration (i.v.) of the muscarinic receptor antagonist
      atropine methyl bromide significantly attenuated ( approximately 62%) the HR
      response whereas, the total autonomic blockade abolished the HR response.
      Finally, unilateral or bilateral microinjection of hcrt-1 into the magnocellular
      reticular nucleus significantly attenuated the reflex bradycardia resulting from
      the activation of the baroreflex following the increase in MAP from an iv
      injection of phenylephrine. These data suggest that hcrt-1 in the RVMM region
      activates neuronal circuits that both inhibit vagal activity and increase
      sympathetic activity to the heart, and that it alters the excitability of central
      circuits that reflexly control the circulation.

PMID- 14575881
TI  - Circadian rhythm and photic control of cAMP level in chick retinal cell cultures:
      a mechanism for coupling the circadian oscillator to the melatonin-synthesizing
      enzyme, arylalkylamine N-acetyltransferase, in photoreceptor cells.
AB  - Arylalkylamine N-acetyltransferase (AANAT) is the penultimate and key regulatory
      enzyme in the melatonin biosynthetic pathway. In chicken retina in vivo, AANAT is
      expressed in a circadian fashion, primarily in photoreceptor cells. AANAT
      activity is high at night in darkness, low during the daytime, and suppressed by
      light exposure at night. In the present study, we investigated the circadian and
      photic regulation of adenosine 3',5'-monophosphate (cAMP) in cultured retinal
      cells entrained to a daily light-dark (LD) cycle, as well as the role of Ca(2+)
      and cAMP in the regulation of AANAT activity. Similar to AANAT activity, cAMP
      levels fluctuate in a daily fashion, with high levels at night in darkness and
      low levels during the day in light. This daily fluctuation continued with reduced
      amplitude in constant (24 h/day) darkness (DD). These changes in cAMP appear to
      be causally related to control of AANAT activity. Adenylyl cyclase and protein
      kinase A inhibitors suppress the nocturnal increase of AANAT in DD, while 8Br
      cAMP augments it. The nocturnal increase of AANAT activity also involves Ca(2+)
      influx, as it is inhibited by nitrendipine, an inhibitor of L-type voltage-gated
      channels, and augmented by Bay K 8644, a Ca(2+) channel agonist. The effect of
      Bay K 8644 was antagonized by the adenylyl cyclase inhibitor MDL 12330A,
      suggesting a link between Ca(2+) influx, cAMP formation, and AANAT activity in
      retinal cells. Light exposure at night, which rapidly suppresses AANAT activity,
      also suppressed cAMP levels. The effect of light on AANAT activity was reversed
      by Bay K 8644, 8Br-cAMP, and the proteasome inhibitor lactacystin. These results
      indicate a dynamic interplay of circadian oscillators and light in the regulation
      of cAMP levels and AANAT activity in photoreceptor cells.

PMID- 14575882
TI  - Intracerebral injection of AMPA causes axonal damage in vivo.
AB  - Brain injury following acute and chronic neurological conditions can involve both
      neuronal perikaryal and axonal damage, yet considerably less is known about the
      mechanisms of axonal damage. Oligodendrocytes and myelin are highly vulnerable to
      AMPA receptor-mediated excitotoxicity. In vitro studies using isolated white
      matter preparations have shown that AMPA receptor-mediated excitotoxicity results
      in axonal damage. The effect of AMPA on axons in vivo remains to be determined.
      We established an in vivo model to determine if axons were vulnerable to AMPA
      mediated toxicity, and furthermore, to examine if axonal damage occurred through
      an AMPA receptor-mediated mechanism. Adult rats received stereotaxic injection of
      AMPA (2.5 or 25 nmol) or vehicle (PBS) into the external capsule. Axonal damage
      was detected in the external capsule and cortex in sections immunostained for
      cytoskeletal components microtubule associated protein-5 (MAP 5), the 200 kDa
      neurofilament subunit (NF 200) and non-phosphorylated neurofilament-H (SMI 32).
      Quantification of axonal damage in the external capsule of MAP 5-immunostained
      sections showed that AMPA caused a significant, dose-dependent increase in axonal
      damage compared to the vehicle-treated controls. AMPA also induced a dose
      dependent increase in myelin and neuronal perikaryal damage. Systemic
      administration of the AMPA receptor antagonist SPD 502 significantly reduced the
      amount of AMPA-induced axonal, myelin and neuronal damage. These data suggest
      that AMPA induces structural damage to the cytoskeleton of axons in vivo, as well
      as neuronal and myelin damage, and that this occurs through AMPA receptor
      mediated mechanisms. AMPA receptor antagonism may have therapeutic potential to
      salvage both axons and neuronal perikarya in a number of neurological disorders.

PMID- 14575883
TI  - Nucleobase adenine as a trophic factor acting on Purkinje cells.
AB  - We examined the influence of nucleobases, nucleosides, nucleotides, and their
      analogs on rat cerebellar Purkinje cells in primary culture and found that the
      number of cultured Purkinje cells was greatly increased by the nucleobase
      adenine. Purkinje cells were cultured for 13 days in vitro in the presence of
      various reagents, and the resulting cell numbers were counted. As a result, the
      nucleobase adenine was most effective at increasing the number of Purkinje cells
      among the reagents tested. In the cultures supplemented with adenine in
      millimolar concentrations (1-2 mM), the number of Purkinje cells was increased by
      up to 30 times the number of Purkinje cells in the control. Adenine had no affect
      on the number of granule cells, and it reduced the number of astrocytes, both of
      which were cocultured in cerebellar primary cultures. Stimulation of
      purinoceptors by adenosine and adenosine 5'-triphosphate (ATP) did not result in
      an increase in the number of Purkinje cells. Furthermore, the adenine effect on
      Purkinje cells was not related to PKA, as determined with the use of a PKA
      inhibitor. Our findings suggest that adenine exerts neurotrophic effects that
      have not been described to date; in particular, the present study demonstrated
      that adenine increases the number of Purkinje cells by an unknown mechanism.

PMID- 14575884
TI  - Peripheral and central proinflammatory cytokine response to a severe acute
      stressor.
AB  - The role of proinflammatory cytokines in the response to acute stressor exposure
      has received recent attention. Exposure to a single session of inescapable shock
      (IS) induces peripheral and central proinflammatory cytokines. Other stressors
      also increase expression of proinflammatory cytokine mRNA and/or protein in
      various tissues. However, the induction of central and peripheral proinflammatory
      cytokines by stressors remains controversial and the pattern of cytokine
      induction is not consistent across stressors. The present experiments sought to
      examine the pattern of the proinflammatory cytokine response to a stressor known
      to cause elevations of IL-1beta protein. mRNA expression for three
      proinflammatory cytokines, IL-1beta, TNF-alpha and IL-6, and IL-1beta protein was
      examined after IS. IS increases IL-1beta mRNA and/or protein in a variety of
      tissues, including hypothalamus, hippocampus, pituitary and spleen. Furthermore,
      IS concomitantly alters IL-1beta mRNA and protein in hypothalamus and spleen,
      while the IL-1beta mRNA increase in pituitary lags behind the increase of IL
      1beta protein. Interestingly, IL-1beta mRNA is elevated in hippocampus 4 h after
      IS, but an increase of IL-1beta protein in hippocampus is not detected.
      Expression of TNF-alpha and IL-6 mRNA do not increase in response to IS. Indeed,
      TNF-alpha mRNA expression decreases in cortex, pituitary and liver immediately
      after IS. These findings suggest that alterations of proinflammatory cytokine
      expression by stressors, and IS in particular, are region- and cytokine-specific.

PMID- 14575885
TI  - Collateral axonal projections from hypothalamic hypocretin neurons to
      cardiovascular sites in nucleus ambiguus and nucleus tractus solitarius.
AB  - Hypocretin-1 (hcrt-1)-containing axons have been shown to have an extensive
      distribution within the central nervous system, although the total number of
      hypothalamic hcrt-1 neurons has been shown to be small. This suggests that hcrt-1
      neurons may innervate central structures with similar function through collateral
      axonal projections. Retrograde tract-tracing techniques combined with
      immunohistochemistry were used in this study to investigate whether hypothalamic
      hcrt-1-containing neurons send collateral axonal projections to cardiovascular
      sites in the nucleus of the solitary tract (NTS) and in the nucleus ambiguus
      (Amb) in the rat. Fluorogold- (FG) and/or rhodamine (Rd)-labeled latex
      microspheres were microinjected into either the NTS or Amb at sites that elicited
      bardycardia responses (L-glutamate; 0.25 M; 10 nl). After a survival period of 10
      15 days, the rats were sacrificed and tissue sections of the hypothalamus were
      processed immunohistochemically for the identification of hcrt-1-containing cell
      bodies. After injection of the tract-tracers into the NTS or Amb, retrogradely
      labeled neurons were observed within several hypothalamic regions; the
      paraventricular hypothalamic nucleus, lateral hypothalamic area, perifornical
      hypothalamic area, and posterior hypothalamus, bilaterally, but with an
      ipsilateral predominance. In addition, after NTS injections, retrogradely labeled
      neurons were found within the ipsilateral caudal arcuate nucleus. Of the total
      number (1107+/-97) of hcrt-1-immunoreactive neurons found bilaterally within the
      lateral and perifornical hypothalamic nuclei, 7.9+/-1.4% were found to be
      retrogradely labeled from the NTS, 16.4+/-1.8% from the Amb, and 3.1+/-0.5% from
      both medullary sites. Hcrt-1 neurons projecting to the NTS were found mainly in
      and around the perifornical hypothalamic region, with a smaller number in the
      caudal lateral hypothalamic area. On the other hand, those innervating the Amb
      were primarily observed within the caudal lateral hypothalamic area, with a
      smaller number in the perifornical hypothalamic area. Neurons with collateral
      axonal projections to NTS and Amb were observed within two specific hypothalamic
      areas: one group of neurons was found in the perifornical hypothalamic area, and
      the other was observed in the lateral hypothalamic region just dorsal to the
      retrochiasmatic component of the supraoptic nucleus. These data indicate that
      axons from hcrt-1 neurons bifurcate to innervate functionally similar
      cardiovascular-responsive sites in the NTS and Amb. Although the function of
      these hcrt-1-containing hypothalamic-medullary pathways is not known, they likely
      represent the anatomical substrate by which the lateral hypothalamic hcrt-1
      neurons simultaneously coordinate autonomic-cardiovascular responses to different
      behaviors.

PMID- 14575886
TI  - Different regulation of adenylyl cyclase and rolipram-sensitive phosphodiesterase
      activity on the frontal cortex and hippocampus in learned helplessness rats.
AB  - The present study examined the activities of adenylyl cyclase (AC) and rolipram
      sensitive phosphodiesterase (PDE4) on brain regions in learned helplessness rat
      in order to clarify the cyclic AMP (cAMP) regulation system in the depressive
      state. Rats exposed to inescapable footshocks once a day for 3 days exhibited a
      significant increase in escape failure on Day 1 (the day after the last
      inescapable shock day) and Day 7. The plasma corticosterone level in rats
      subjected to inescapable shocks was significantly higher than that of nonstressed
      control rats on Days 1 and 7. The PDE4 activity of the frontal cortex was
      significantly lower than that of nonstressed control rats on Day 1. However, on
      Day 7, the PDE4 and [3H]-rolipram binding activities were significantly increased
      in the frontal cortex and hippocampus of learned helplessness rats compared with
      those of nonstressed control rats. Forskolin-stimulated AC activity was
      significantly decreased in the frontal cortex, hippocampus and striatum of
      learned helplessness rats on Day 1, but not on Day 7. Thus, a decrease in both AC
      and PDE4 activities was noted in the acute depressive state. In contrast,
      increase of PDE4 activity was noted in the delayed depressive phase, although no
      change of AC activity was observed. Gel shift assays also showed the decrease of
      cAMP-response element (CRE)-binding activity relating to cAMP activity in the
      frontal cortex and hippocampus of learned helplessness rats on Days 1 and 7.
      These findings indicated a delayed increase in PDE4 activity leading to
      hypofunction of the cAMP-dependent signal transduction system in the frontal
      cortex and hippocampus of learned helplessness rats, suggesting that up
      regulation of the cAMP-degradation system by PDE4 may play a pivotal role in
      pathological states of chronic depression.

PMID- 14575888
TI  - Lens epithelium-derived growth factor: neuroprotection on rat retinal damage
      induced by N-methyl-D-aspartate.
AB  - The purpose of this study is to investigate possible neuroprotective effects of
      lens epithelium-derived growth factor (LEDGF) against cell death induced by N
      methyl-D-aspartate (NMDA) in the rat retina. LEDGF and/or NMDA were
      intravitreally injected into rat eyes. NMDA-induced retinal death and protective
      effects of LEDGF were evaluated by morphometric analysis, cell numbers in the
      ganglion cell layer (GCL) and the thickness of the inner plexiform layer (IPL).
      Retrograde labeling with a fluorescent tracer (Fluoro-Gold) was applied for
      counting retinal ganglion cells (RGCs) that survived after NMDA injection.
      Terminal deoxyribonucleotidyl transferase (TdT)-mediated fluroscein-16-dUTP nick
      end-labeling (TUNEL) staining was used to evaluate of retinal cell death.
      Morphometric analysis and retrograde labeling analysis showed that retinal damage
      induced by NMDA was protected significantly by LEDGF. TUNEL assay revealed that
      pretreatment with LEDGF prevents NMDA-induced apoptosis. Retinal damage (ganglion
      and amacrine cells) induced by NMDA was protected by an intravitreal injection of
      LEDGF.

PMID- 14575887
TI  - Sprouting of axon-like processes from axotomized retinal ganglion cells induced
      by normal and preinjured intravitreal optic nerve grafts.
AB  - The failure of axonal regeneration in the mammalian central nervous system (CNS)
      is currently attributed to the glial environment of the lesion site which
      elaborates a multitude of inhibitory factors. Less attention has been paid to the
      potential of trophic support associated with the CNS, especially in relation to
      the status of the damaged CNS after an injury has been evoked. Using a grafting
      paradigm to implant an optic nerve (ON) segment into the vitreous, we have
      addressed how a prior damage of the ON before grafting influences its ability to
      stimulate retinal ganglion cells (RGCs) to sprout axon-like processes. Our
      results showed that a normal noninjured ON implanted intravitreally stimulated
      sprouting of RGCs, as revealed by sliver staining of the sprouting cells, as well
      as increasing the number of RGCs which express GAP-43. A prior crush injury of
      the ON 7 days before its implantation into the vitreous resulted in a significant
      decrease in its ability to stimulate RGC sprouting when the crush lesion segment
      was used as the graft, whereas grafts taken from segments proximal and distal to
      the lesion segment had potencies similar to that of the noninjured graft. Both
      astrocytes and oligodendrocytes were drastically reduced in number in the lesion
      segment graft, suggesting their involvement in the secretion of soluble trophic
      factors that may play a role in the sprouting and regeneration of damaged
      neurons.

PMID- 14575889
TI  - Glycinergic input to carp retinal ganglion cells may be mediated by glycine
      receptors with homologous kinetics.
AB  - Current responses of carp retinal ganglion cells (RGCs) retrogradely labeled and
      freshly dissociated to rapid application of glycine were recorded by whole-cell
      patch clamp techniques and effects of glycine antagonists on these responses were
      analyzed. The current response to maintained application of glycine at a
      concentration higher than 30 microM exhibited desensitization, which was well
      fitted to a monoexponential function. Strychnine (1 microM), a glycine receptor
      antagonist, completely blocked the response to 100 microM glycine. Strychnine at
      a concentration range between 10 and 200 nM suppressed the response to 100 microM
      glycine in a dose-dependent manner, and only a slow-activated and sustained
      current eventually remained in the presence of 200 nM strychnine. Power spectral
      density (PSD) analysis revealed no changes in the density-frequency dependence
      caused by strychnine. It was further shown that dissociation of strychnine from
      glycine receptors was rather slow. Moreover, Zn(2+) exerted similar dual action
      on this sustained response and the response in Ringer's: potentiating and
      reducing them at low and high concentrations of Zn(2+), respectively. 5,7
      Dichlorokynurenic acid (DCKA, 500 microM), a selective blocker of the glycine
      recognition site at the NMDA receptor, partially reduced the glycine response,
      but without changing its kinetics. These results suggest that glycinergic input
      to carp ganglion cells may be mediated by strychnine-sensitive glycine receptors
      with homologous kinetics, and slow dissociation of strychnine from glycine
      receptors may partially account for the changes in glycine response kinetics
      occurring in the presence of strychnine.

PMID- 14575890
TI  - In vivo and in vitro effects of proline on some parameters of oxidative stress in
      rat brain.
AB  - Hyperprolinemia type II is an autosomal recessive disorder caused by the severe
      deficiency of delta(1)-pyrroline-5-carboxylate dehydrogenase activity leading to
      tissue accumulation of proline (Pro). Most patients detected so far show
      neurological manifestations including epilepsy and mental retardation, whose
      pathophysiology is not yet fully established. In the present study, we determined
      the in vivo and in vitro effects of Pro on some parameters of oxidative stress,
      namely chemiluminescence, total radical-trapping antioxidant potential (TRAP) and
      the activity of the antioxidant enzymes catalase (CAT), glutathione peroxidase
      (GSH-Px) and superoxide dismutase (SOD) from cerebral cortex of 29-day-old Wistar
      rats. Results showed that acute administration of Pro provoked a significant
      increase of chemiluminescence and a decrease of TRAP, whereas chronic
      administration of the metabolite did not alter these parameters. Furthermore, in
      vitro brain exposure to Pro resulted in increased chemiluminescence and decreased
      TRAP at Pro concentrations similar to those observed in tissues of
      hyperprolinemic patients (0.5-1.0 mM). As regards to the antioxidant enzymes,
      acute injection of Pro significantly decreased CAT activity and did not alter SOD
      and GSH-Px activities, whereas chronic Pro administration provoked a significant
      increase of CAT activity, a decrease of GSH-Px activity and did not modify SOD
      activity. Furthermore, CAT, GSH-Px and SOD activities were not affected by the
      presence of Pro in the incubation medium. The data indicate that Pro induces
      oxidative stress in vivo and in vitro, which may be involved in the brain
      dysfunction observed in hyperprolinemic patients.

PMID- 14575891
TI  - Arachidonic acid peroxides induce apoptotic Neuro-2A cell death in association
      with intracellular Ca(2+) rise and mitochondrial damage independently of caspase
      3 activation.
AB  - The present study aimed at understanding the effects of arachidonic acid
      peroxides on neuronal cell death using the mouse neuroblastoma cell line, Neuro
      2A cells. Arachidonic acid peroxides were produced by ultraviolet (UV) radiation.
      UV-radiated arachidonic acid significantly reduced Neuro-2A cell viability at
      concentrations of more than 0.1 muM, with being more potential than non-radiated
      arachidonic acid. Nuclei of Neuro-2A cells killed with UV-radiated arachidonic
      acid were reactive to Hoechst 33342, a marker of apoptosis, and the effect was
      much greater than that achieved with non-radiated arachidonic acid. UV-radiated
      arachidonic acid persistently increased intracellular Ca(2+) concentrations and
      dissipated mitochondrial membrane potential in Neuro-2A cells. UV-radiated
      arachidonic acid-induced Neuro-2A cell death, whereas it was not affected by a
      pancaspase inhibitor or a caspase-3 inhibitor, was significantly inhibited by an
      inhibitor of caspase-1, -8, or -9. The results of the present study suggest that
      arachidonic acid peroxides induce apoptotic neuronal cell death in association
      with intracellular Ca(2+) rise and mitochondrial damage, in part via a caspase
      dependent pathway regardless of caspase-3.

PMID- 14575892
TI  - Impairments of ERK signal transduction in the brain in a rat model of depression
      induced by neonatal exposure of clomipramine.
AB  - Depression is associated with deficiencies in monoaminergic transmitters and
      possibly neurotrophins. A common cellular response to these molecules is the
      activation of extracellular signal-regulated kinase (ERK). A deficiency of ERK
      signal transduction in depression was therefore hypothesized and was tested in a
      rat model of depression, produced by neonatal treatment with clomipramine (CLI).
      We measured sexual behaviors and brain levels of ERK, phosphorylated ERK (pERK),
      protein phosphatase 1 (PP1), and MAPK phosphatase-2 (MKP-2) during adulthood in
      control and neonatally CLI-treated rats (CLI rats). As expected, the CLI rats
      exhibited significantly lower sexual activities and also exhibited (1).
      significant decreases of pERK1/2 in the frontal cortex and pERK1 in the
      hippocampus, (2). slight but significant reduction of ERK2 in the frontal cortex
      and hippocampus, (3). no change of pERK1/2 levels in the temporal cortex,
      occipital cortex, parietal cortex, midbrain, and medulla, (4). significantly
      higher levels of PP1 in both the frontal cortex and hippocampus, (5). no change
      in MKP-2 in any examined region, and (6). all five measures of sexual function
      were significantly correlated with ERK2 and pERK2 in the frontal cortex. These
      findings suggest that a deficiency in the ERK signaling pathway is involved in
      the display of depressive behaviors.

PMID- 14575893
TI  - Evidence for a mu-opioid-opioid connection between the paraventricular nucleus
      and ventral tegmental area in the rat.
AB  - The paraventricular nucleus (PVN) and the ventral tegmental area (VTA) have been
      shown to be involved in opioid mediated feeding behavior. The present study
      examined whether mu-opioid signalling between the PVN and VTA affected feeding
      behavior. Male Sprague-Dawley rats were cannulated with one cannula placed in the
      PVN and two cannulae placed in the VTA, which allowed for co-administration of
      the mu-opioid receptor agonist [D-Ala(2), NMe-Phe(4), Gly-ol(5)]-enkephalin
      (DAMGO) in one site and the opioid antagonist naltrexone (NTX) in the other site.
      Bilateral administration of DAMGO (1.2, 2.4 and 4.9 nmol) into the VTA stimulated
      feeding dose dependently at 2.4 and 4.9 nmol (P<0.05). The DAMGO (2.4 nmol)
      induced increase of food intake following injection into the PVN was blocked by
      bilateral injection of NTX (6.6, 13.2 and 26.5 nmol) into the VTA at 2 and 4 h
      (P<0.05). In the reverse situation, the DAMGO (2.4 nmol)-induced increase of food
      intake following injection into the VTA was blocked by injection of NTX (13.2 and
      26.5 nmol) into the PVN at 2 and 4 h (P<0.05). The present study suggests that a
      bidirectional mu-opioid-opioid signalling pathway exists between the PVN and the
      VTA which influences feeding.

PMID- 14575894
TI  - Hippocampal serotonergic system is involved in anxiety-like behavior induced by
      corticotropin-releasing factor.
AB  - To clarify the interaction between anxiety-like behavior produced by
      corticotropin-releasing factor (CRF) and the 5-HT system, we investigated the
      effects of intracerebroventricular (i.c.v.) administration of CRF on an elevated
      plus-maze performance as indices of anxiety, measuring extracellular levels of 5
      HT in the ventral hippocampus using an in vivo brain dialysis method in rats. The
      time spent in the open arms of the maze and the number of open arm entries were
      decreased in a dose-dependent manner by the administration of CRF (0.3-1.0
      microg/rat). These effects of CRF were prevented by pretreatment with a 5-HT(1A)
      receptor agonist, 8-OH-DPAT (0.5 mg/kg, s.c.). In biochemical studies, CRF
      increased 5-HT release about 150-250% above baseline in the ventral hippocampus
      and this elevation was significantly inhibited by a CRF receptor antagonist,
      alpha-Helical CRF(9-41) (50 mug/rat), and 5-HT(1A) receptor agonist, 8-OH-DPAT
      (0.5 mg/kg, s.c.). These results suggested that the anxiety-like effect produced
      by CRF may have involved increased 5-HT transmission in the ventral hippocampus.
      Taken with the evidence for hypersecretion of CRF in patients with depression and
      anxiety-related disorders, our findings lead to the intriguing hypothesis that
      interaction between CRF and 5-HT, especially in the ventral hippocampus, plays a
      role in the etiology of affective and anxiety disorders.

PMID- 14575895
TI  - Effect of nicotine on the expression of leptin and forebrain leptin receptors in
      the rat.
AB  - We have previously reported that chronic nicotine administration (4.0 mg/kg/day
      by i.p. injection over 14 days) up-regulates orexin/hypocretin and neuropeptide Y
      (NPY) mRNA expression and peptide levels within the hypothalamus. Since there
      exists a coregulation between these neuropeptides and the protein leptin, the
      present study was undertaken to determine whether nicotine has a regulatory
      effect on leptin signaling. Under the same experimental regimen used previously,
      we found that nicotine down-regulates plasma leptin concentration by 48.8%
      (P<0.001) and leptin RNA level by 11.4% and 12.4%, respectively, in the perirenal
      and epididymal white adipose tissue (PWAT, EWAT) compared to the saline controls.
      We also measured an approximately 20% decrease in white and brown adipose tissue
      (BAT) by weight in nicotine-treated animals relative to saline controls (P<0.05).
      On the other hand, we found that chronic nicotine administration increased the
      expression levels of OB-Rb mRNA by 12% and OB-R mRNA by 25% in the medial basal
      hypothalamus compared to control rats. Subsequent radioligand binding assays
      indicated that nicotine also significantly increased leptin binding in
      ventromedial hypothalamic area (VMA), medial basal hypothalamic area (MBA),
      arcuate nucleus/median eminence, paraventricular nuclei and piriform cortex.
      Taken together, our results revealed that nicotine is involved in the regulation
      of leptin signaling, suggesting that leptin and its receptor play a role in the
      anorectic effects of nicotine on food intake and body weight in rats.

PMID- 14575896
TI  - Prolonged effects of repeated cocaine on medial prefrontal cortex dopamine
      response to cocaine and a stressful predatory odor challenge in rats.
AB  - The present study examined the effects of seven daily saline (1 ml/kg, i.p.) or
      cocaine injections (15 mg/kg, i.p.) on extracellular dopamine levels in the
      medial prefrontal cortex (mPFC) after challenge with cocaine or stressful
      predatory odor presentation given 1 week (early withdrawal) or 3 weeks later
      (late withdrawal). Cocaine challenge at early withdrawal produced an increase in
      dopamine levels that was temporally shifted so that maximal levels of dopamine
      were significantly higher and attained 20 min earlier in the cocaine-pretreated
      group (maximal levels of saline controls=378% increase, cocaine=494% increase
      above baseline). Cocaine challenge at late withdrawal produced a similar effect
      on the temporal shift of maximal dopamine levels, with a significantly higher
      maximal percent increase of dopamine in cocaine-pretreated rats (saline
      pretreated=420% increase, cocaine-pretreated=515% increase). Challenge with TMT,
      a predatory odor from fox that produces a stress response in rats, produced a
      maximal 75-200% increase in basal dopamine levels in both groups at both early
      and late withdrawal times. As with cocaine challenge, daily cocaine produced a
      leftward shift in the time at which maximal dopamine levels were attained in
      response to TMT. Cocaine-pretreated animals demonstrated maximal dopamine levels
      40-80 min after TMT removal, while saline-pretreated rats showed maximal levels
      100-140 min after TMT removal. These results suggest that there are long-term
      changes in the mPFC dopamine response to subsequent challenge with cocaine as
      well as a stressful predatory odor. The altered response of mPFC dopamine after
      repeated daily cocaine may impact relapse to drug-seeking or drug-taking
      behavior.

PMID- 14575897
TI  - Interrelationships between mu opioid and melanocortin receptors in mediating food
      intake in rats.
AB  - The present study examined the interrelationships between feeding responses
      produced by mu opioid receptor agonists and melanocortin-3 or 4 (MC-3/4) receptor
      antagonists. Feeding induced by the mu-sensitive opioid peptide, beta-endorphin
      (betaEND, 10 microg, i.c.v.) was significantly and dose-dependently reduced by
      pretreatment with the MC-3/4 receptor agonist, melanotan-II (MTII: 0.01-10 nmol,
      i.c.v.). Moreover, the selective mu opioid antagonist, beta-funaltrexamine
      (betaFNA: 2-20 mug, i.c.v.), significantly and dose-dependently reduced feeding
      and weight gain elicited by the potent MC-3/4 receptor antagonist, SHU-9119 (0.5
      nmol, i.c.v.), especially at those intake periods (24-48 h) when SHU-9119
      produced maximal ingestive effects. These data extend previous findings
      demonstrating interactions between opioid and melanocortin receptors in the
      mediation of food intake.

PMID- 14575898
TI  - Contralateral representation of tongue thermal information in the rat thalamus.
AB  - Twenty-six thalamic neurons receiving innocuous thermal inputs from the tongue
      were identified in a limited region extending from the dorsomedial region of the
      posteromedial ventral nucleus to the dorsolateral region of the parvicellular
      part. Nine neurons had a cold receptive field and one neuron had neighboring cold
      and warm receptive fields on the anterior tongue contralateral to the recording
      side.

PMID- 14575899
TI  - Mecamylamine reduces nicotine cross-desensitization of trigeminal caudalis
      neuronal responses to oral chemical irritation.
AB  - We investigated the role of neuronal nicotinic acetylcholine receptors (nAChRs)
      in nicotine cross-desensitization of chemonociceptive responses of trigeminal
      subnucleus caudalis (Vc) neurons in rats. Vc responses to lingually applied
      pentanoic acid were significantly reduced following nicotine, and this was
      prevented when the nAChR antagonist mecamylamine was applied before or after
      nicotine. A peripheral site of nicotine cross-desensitization is suggested via a
      nAChR-mediated reduction in acidic excitation of lingual nociceptors that project
      to Vc.

PMID- 14575900
TI  - Astroglial activation accompanies heat shock protein upregulation in rat brain
      following single oral dose of geranylgeranylacetone.
AB  - Geranylgeranylacetone (GGA), more commonly known as an antiulcer agent,
      reportedly induces the heat shock protein 70 (HSP70) family in the gastric
      mucosa, liver and heart of rats. However, it has not been reported whether HSPs,
      and other factors that contribute to neuroprotection, are inducible in the brain
      following a single oral dose of GGA. The present study evaluated the consequences
      of oral GGA on astrocytic activation and the expression of HSP and revealed that
      a single oral dose caused a transient increase in the immunoreactivity (IR) of
      HSP70 and glial fibrillary acidic protein (GFAP) in the hippocampus of the rat
      brain.

PMID- 14575901
TI  - Epileptogenic activity induced by histamine H(1) antagonists in amygdala-kindled
      rats.
AB  - The epileptogenic activities induced by histamine H(1) antagonists in amygdala
      kindled rats were studied in comparison with activities in nonkindled rats (sham
      rats). Intraperitoneal injection of pyrilamine, diphenhydramine and ketotifen
      resulted in behavioral and electroencephalogram (EEG)-detected seizures in
      amygdala-kindled rats at doses which caused no or negligible seizures in sham
      rats. On the other hand, loratadine and cetirizine caused no behavioral or EEG
      seizures in either amygdala-kindled or sham rats even at a dose of 40 mg/kg. In
      conclusion, first-generation H(1) antagonists likely elicit epileptogenic
      activity in amygdala-kindled rats more potent than that in sham rats.

PMID- 14575902
TI  - A K(+) channel activated by cholinergic muscarinic receptors in chick ciliary
      ganglion neurons at early developmental stage.
AB  - Embryonic chick ciliary ganglion (CG) neurons obtained from E7-E8 ganglia
      maintained in serum-free medium were stimulated with 50 microM muscarine. A fast
      hyperpolarization of the membrane potential was observed in 25% of the cells
      tested, that in some cases was associated with a slower depolarization.
      Accordingly, in voltage clamp experiments, either an outward current or a
      biphasic current response could be observed. Single-channel experiments provide
      evidence that these signals can be associated to the activation of a K(+) channel
      whose conductance is 20 pS.

PMID- 14575903
TI  - Convergent effects of oxytocin and a delta-opioid agonist in the bed nuclei of
      the stria terminalis of the peripartum rat.
AB  - In the bed nuclei of the stria terminalis (BST), opioids may suppress the
      facilitatory effect of oxytocin on its own release pre-partum. In vitro
      electrophysiological recording showed that in virgin, late-pregnant, and
      lactating rats, a delta-opioid agonist inhibited a high proportion of BST
      neurons, many of which were also oxytocin responsive. Response magnitude did not
      differ significantly between groups, suggesting that the postulated pre-partum
      increase in opioid tone does not involve postsynaptic changes in neuronal
      sensitivity.

PMID- 14575904
TI  - Post-weaning social isolation of rats leads to a diminution of LTP in the CA1 to
      subiculum pathway.
AB  - Post-weaning social isolation of rats produces psychological and physiological
      changes that are relevant to schizophrenia. Here, we report that long-term
      potentiation (LTP) in the CA1 to subiculum pathway is lower by 34%, (P<0.0001) in
      brain slices from isolates compared with those from socially housed rats. We also
      report that LTP in this pathway is NMDA receptor-dependent.

PMID- 14575905
TI  - In vivo insular cortex LTP induced by brain-derived neurotrophic factor.
AB  - Recent studies suggest that brain-derived neurotrophic factor (BDNF) plays a
      critical role in long-term synaptic plasticity in the adult brain. Previous
      studies on the insular cortex (IC), a region of the temporal cortex implicated in
      the acquisition and storage of different aversive learning tasks, have
      demonstrated that tetanic stimulation of the basolateral nucleus of the amygdala
      (Bla) induces an N-methyl-D-aspartate (NMDA)-dependent form of long-term
      potentiation (LTP) in the IC of adult rats in vivo. Here, we show that acute
      intracortical microinfusion of BDNF induces a lasting potentiation of synaptic
      efficacy in the Bla-IC projection of anesthetized adult rats. This constitutes an
      in vivo demonstration of neurotrophin-induced potentiation of synaptic
      transmission in the neocortex. These findings support the concept that BDNF could
      be a synaptic messenger involved in activity-dependent synaptic plasticity.

PMID- 14575906
TI  - Genetic analysis of multiple sclerosis in Europeans.

PMID- 14575907
TI  - The genetic epidemiology of multiple sclerosis.
AB  - Multiple sclerosis (MS) is a debilitating immunological and neurodegenerative
      disorder. Epidemiological studies have provided overwhelming evidence of complex
      genetic susceptibility to MS. However, with the exception of the human leukocyte
      antigen (HLA) locus, genetic studies have failed to consistently identify
      significant linkage or association with genes that modulate MS disease
      expression. Numerous functional candidate gene studies, linkage genomic screens,
      and locational candidate gene studies have been performed in an attempt to
      identify additional loci. However, these methods have demonstrated insufficient
      power to consistently identify genes or epigenetic factors for MS. More current
      approaches integrate information from a variety of sources (e.g. consistent
      linkage data, gene expression profiling, and functional characterization studies)
      and utilize high throughput methods (e.g. genotyping high density markers,
      utilizing pooling schemes and performing new statistical analyses) in an attempt
      to overcome power issues. The following article presents a review of MS genetics
      research and a brief overview of methods that are currently being developed and
      utilized for fine localization of MS loci, such as the method employed in the
      Genetic Analysis of Multiple sclerosis in EuropeanS (GAMES) study that is
      presented elsewhere in this journal. It is the hope of researchers that these
      methods will lead to the identification of susceptibility genes for MS that aid
      in elucidating pathogenic mechanisms and potential therapeutic strategies for
      this debilitating disease.

PMID- 14575908
TI  - The genetic analysis of multiple sclerosis in Europeans: concepts and design.

PMID- 14575909
TI  - A whole genome screen for linkage in Turkish multiple sclerosis.
AB  - Factors exerting recessive effects on susceptibility to complex traits are
      expected to be over-represented in communities having a higher frequency of
      consanguineous marriage. Multiple sclerosis, a typical complex trait, is
      relatively common in Turkey where cultural factors also determine a high rate of
      consanguineous marriage. Previous genetic studies of multiple sclerosis in Turkey
      have been confined to the search for associations with candidate genes. In order
      to exploit the special genetic features of the Turkish population, we performed a
      whole genome screen for linkage in 43 Turkish multiplex families employing 392
      microsatellite markers. Two genomic regions where maximum lod score (MLS) values
      were suggestive of linkage were identified (chromosomes 13q and 18q23) along with
      a further 14 regions of potential linkage. Parametric analysis of these data
      using a recessive model, appropriate for populations with a high frequency of
      consanguinity, increased the LOD scores in four regions.

PMID- 14575910
TI  - Updated results of the United Kingdom linkage-based genome screen in multiple
      sclerosis.
AB  - In 1996, we reported the results of a linkage genome screen based on 129 UK
      multiple sclerosis multiplex families, together with follow-up typing of
      interesting regions in a second set of families. We have now completed screening
      the remainder of the genome in this second set of United Kingdom families by
      typing 242 microsatellite markers. These data have been analysed together with
      those previously published, resulting in the largest currently available whole
      genome linkage dataset from a single population in multiple sclerosis. Four new
      regions of potential linkage (chromosomes 10p, 11p, 19p, 20p) not previously
      described were identified. In the combined analysis of all 226 families, a total
      of five regions of suggestive linkage are seen (chromosomes 1p, 6p, 14q, 17q,
      Xq), where only one would have been expected to occur by chance alone.

PMID- 14575911
TI  - Refining the linkage analysis on chromosome 10 in 449 sib-pairs with multiple
      sclerosis.
AB  - Genome-wide screens for linkage in multiplex families with multiple sclerosis
      (MS) from United Kingdom, Sardinia, Italy and the Nordic countries (Denmark,
      Finland, Norway and Sweden) have each shown suggestive or potential linkage on
      chromosome 10. The partially overlapping regions identified by these studies
      encompass around 60 cM of the chromosome. In order to explore this region
      further, we typed 13 microsatellite markers in the same 449 families originally
      studied in the individual screens. This additional genotyping increased the
      information extraction in the region from 52% to 79% and revealed increased
      support for linkage (MLS 2.5) peaking at 10p15.

PMID- 14575912
TI  - A meta-analysis of whole genome linkage screens in multiple sclerosis.
AB  - Linkage studies in complex diseases like multiple sclerosis, where the effects
      attributable to individual loci are modest, are critically dependent upon the
      number of families included. We have combined the raw genotyping data from all
      published genome linkage screens in multiple sclerosis and thereby performed a
      linkage analysis including 719 families studied with a weighted average of 359
      microsatellite markers per family (range 257-453) providing an average marker
      separation of 10.2 cM. Linkage with genome-wide significance is confirmed in the
      HLA region on chromosome 6p21. In addition, two novel regions suggestive of
      linkage are seen (17q21 and 22q13). Our simulations would imply that the number
      of peaks with NPL scores >/=2.1 exceeds the number expected by chance alone.

PMID- 14575913
TI  - Statistical analysis of the GAMES studies.

PMID- 14575914
TI  - Refining the analysis of a whole genome linkage disequilibrium association map:
      the United Kingdom results.
AB  - Individual genotyping of the 10 most promising markers identified in our
      previously reported screen for linkage disequilibrium (LD) in multiple sclerosis
      identified a number of effects which confound the analysis and are of general
      importance in the interpretation of results obtained using microsatellite markers
      typed in pooled DNA. In order to identify and characterise these effects, we
      individually genotyped 529 promising markers in 16 trio families. We then devised
      adapting factors, which were designed to correct for these confounders. This more
      extensive analysis of the previously published UK data set and the repeat
      analyses incorporating these adaptations led to the identification of two novel
      markers that may be associated with multiple sclerosis in this population,
      providing a close correlation between the results of pooled analysis and
      individual typing.

PMID- 14575915
TI  - A genome-wide screen for linkage disequilibrium in Australian HLA-DRB1*1501
      positive multiple sclerosis patients.
AB  - The association of multiple sclerosis with alleles/haplotypes from the HLA region
      on chromosome 6p21 is well established although the remainder of the genome
      remains relatively unexplored. We have completed a genome-wide screen for linkage
      disequilibrium in a cohort of Australian multiple sclerosis patients positive for
      HLA-DRB1*1501. A total of 4346 microsatellite markers provided through the
      "Genetic Analysis of Multiple sclerosis in EuropeanS" (GAMES) collaborative were
      analysed in DNA separately pooled from cases (n=217) and controls (n=187).
      Associations were found in four genomic regions (12q15, 16p13, 18p11 and 19q13)
      previously identified in linkage genome screens. Three additional regions of
      novel association were also identified (11q12, 11q23 and 14q21). Further analysis
      of these regions is required to establish whether the associations observed are
      due to epistatic interaction with the HLA locus.

PMID- 14575916
TI  - New candidate loci for multiple sclerosis susceptibility revealed by a whole
      genome association screen in a Belgian population.
AB  - We have completed a whole genome screen for association with multiple sclerosis
      (MS) in a Belgian population. The 6000 microsatellite markers provided through
      the Genetic Association of Multiple Sclerosis in EuropeanS (GAMES) collaborative
      were genotyped in case-control and family-based samples. The 20 most promising
      markers included three markers (D6S1615, D6S2444 and TNFa) from the classically
      established HLA class II cluster and one (D6S265) from the recently re-emphasized
      HLA class I cluster. In other highlighted regions, preliminary candidate genes
      from the immune system have been identified: e.g. the integrin ligand EDIL3, the
      high-mobility group box protein TOX, neutral sphingomyelinase activating factor
      (NSMAF) and the B-cell specific transcription factor POU2AF1.

PMID- 14575917
TI  - A whole genome association study in Finnish multiple sclerosis patients with 3669
      markers.
AB  - Multiple sclerosis (MS) is a demyelinating disease of the central nervous system
      with complex genetic background. In the present study, based in the Finnish
      population, we typed a large number of microsatellite markers in separately
      pooled DNA samples from 195 MS patients and 205 controls. A total of 108 markers
      showed evidence of association. Five genomic regions containing two or more of
      these markers within a 1-Mb interval were identified, 1q43, 2p16, 4p15, 4q34 and
      6p21 (the MHC region). Substantial overlap with previously published linkage
      genome screens is also seen.

PMID- 14575918
TI  - Genetic analysis of multiple sclerosis in Europeans: French data.
AB  - We report the results of a genome-wide screen for linkage disequilibrium (LD) in
      multiple sclerosis (MS) performed on 200 cases, 200 controls and 200 case-parent
      trios from France employing pooled DNA methodology. A total of 3510
      microsatellite markers supplied through the GAMES collaborative were analysed and
      ranked according to their evidence for association. The most promising 117
      markers were then followed up in a two-step validation process. In the first
      step, additional PCR of the DNA pools was performed in order to refine the
      ranking order. In the second step, markers were genotyped in individual cases and
      parents from the trio families. Seven markers showing nominally significant
      allele frequency differences between affected and unaffected emerged-D6S265,
      D12S1064, TNFa, D7S1824, D14S1426, D14S605 and D21S2051. These potential
      associations will require confirmation in further studies.

PMID- 14575919
TI  - A genome-wide German screen for linkage disequilibrium in multiple sclerosis.
AB  - We report on a genome-wide screen for association with multiple sclerosis (MS) in
      the German population performed using 6000 microsatellite markers. These markers
      were typed in four DNA pools consisting of 234 MS patients (cases), 209 unrelated
      controls, 68 index patients from trio families and their 136 parents (related
      controls). Stringent analysis identified 11 markers showing apparent evidence for
      association. Five from regions previously identified in linkage studies and two
      from the MHC region on chromosome 6p21. These MHC markers are known to be in
      linkage disequilibrium with HLA class II alleles influencing susceptibility to
      MS. The identification of these markers serves as an important positive control.

PMID- 14575920
TI  - A genome-wide screen for association in Hungarian multiple sclerosis.
AB  - Although the pathogenesis of multiple sclerosis (MS) is not fully understood,
      substantial evidence points to the involvement of genetic factors. We report on a
      genome-wide screen for disease association in the Hungarian population using 5532
      microsatellite markers. These markers were typed in DNA pools that consisted of
      88 MS patients (cases), and 128 unrelated controls. Based on a stringent
      selection criterion, we obtained 33 markers suggesting association with the
      disease.

PMID- 14575921
TI  - A whole genome association study in Icelandic multiple sclerosis patients with
      4804 markers.
AB  - Multiple sclerosis (MS) is a demyelinating disorder of the central nervous system
      (CNS) with a complex genetic background. Here we use a genome-wide association
      strategy with 4804 microsatellite markers successfully typed in separately pooled
      DNA from 200 patients and 200 controls. A total of 91 markers showed evidence of
      association. When compared to our in-house physical map of the genome, six 2-Mb
      regions containing at least two of these markers were detected. Of those, three
      regions have one or more markers among the 20 most strongly associated:
      chromosomes 3q25, 6p21.3 (the MHC region) and 19q13.

PMID- 14575922
TI  - A genome wide scan for association with multiple sclerosis in a N. Irish case
      control population.
AB  - In order to screen the genome for linkage disequilibrium (LD) in multiple
      sclerosis (MS), we typed 2537 microsatellite markers in separately pooled DNA
      from 200 cases and 200 controls from N. Ireland. Twenty two markers showing
      significant evidence of association were identified including three from the HLA
      region on chromosome 6p21. Putative candidate genes mapping close to the 19 novel
      markers include the IL10RA and CD3E genes on 11q23 (which both lie close to the
      marker D11S1998). Individual typing of the marker D11S1998 confirmed its
      association.

PMID- 14575923
TI  - A whole genome screen for linkage disequilibrium in multiple sclerosis performed
      in a continental Italian population.
AB  - We have systematically screened the genome for evidence of linkage disequilibrium
      (LD) with multiple sclerosis (MS) by typing 6000 microsatellite markers in case
      control and family based (AFBAC) cohorts from the Italian population. DNA pooling
      was used to reduce the genotyping effort involved. Four DNA pools were
      considered: cases (224 Italian MS patients), controls (231 healthy Italians),
      index (185 index cases from trio families) and parents (the 370 parents of the
      patient included in the Index pool), respectively. After refining analysis of the
      most promising 14 markers to emerge from this screening process, only marker
      D2S367 retained evidence for association.

PMID- 14575925
TI  - A whole genome screen for association in Polish multiple sclerosis patients.
AB  - We have performed the first systematic search for MS susceptibility genes
      completed in the Polish population. This screen was performed using 6000
      microsatellite markers typed in pooled DNA from cases (n=200), controls (n=200)
      and trio families (n=129). Five associated markers are identified, one (D6S2444)
      from the HLA region and four are from novel regions not previously associated
      with MS, 2p16 (D2S2153), 3p13 (D3S3568), 7p22 (D7S2521) and 15q26 (D15S649).

PMID- 14575924
TI  - Two genome-wide linkage disequilibrium screens in Scandinavian multiple sclerosis
      patients.
AB  - We report the first two genome-wide screens for linkage disequilibrium between
      putative multiple sclerosis (MS) susceptibility genes and genetic markers
      performed in the genetically homogenous Scandinavian population, using 6000
      microsatellite markers and DNA pools of approximately 200 MS cases and 200
      controls in each screen. Usable data were achieved from the same 3331 markers in
      both screens. Nine markers from eight genomic regions (1p33, 3q13, 6p21, 6q14,
      7p22, 9p21, 9q21 and Xq22) were identified as potentially associated with MS in
      both screens.

PMID- 14575926
TI  - A whole genome screen for association with multiple sclerosis in Portuguese
      patients.
AB  - Multiple sclerosis (MS) is common in Europe affecting up to 1:500 people. In an
      effort to identify genes influencing susceptibility to the disease, we have
      performed a population-based whole genome screen for association. In this study,
      6000 microsatellite markers were typed in separately pooled DNA samples from MS
      patients (n=188) and matched controls (n=188). Interpretable data was obtained
      from 4661 of these markers. Refining analysis of the most promising markers
      identified 10 showing potential evidence for association.

PMID- 14575927
TI  - A whole genome association study in multiple sclerosis patients from north
      Portugal.
AB  - Genetic factors are known to influence susceptibility to multiple sclerosis (MS)
      but the genes involved are largely undefined. Here, we report an association
      study based on 200 patients and 200 controls from the Porto region in Portugal. A
      total of 3974 markers were successfully typed from which we have identified 46
      markers showing evidence of association. When compared to a physical map three
      regions were found with two of these markers less than 1.5 Mb apart: chromosomes
      6p21.3 (the MHC region), 6q14.1 and 7q34.

PMID- 14575928
TI  - A genome-wide screen for linkage disequilibrium in Sardinian multiple sclerosis.
AB  - Using indirect whole genome association screening, we have searched for multiple
      sclerosis susceptibility genes in the genetically isolated high risk Sardinian
      population. Two screens were performed; the first was based on 229 cases and 264
      unrelated controls, and the second on 235 trio families. Each screen employed a
      dense set of microsatellite markers and DNA pooling. Data from both screens were
      available from 2764 markers. Nine markers showed nominally significant results in
      both screens independently. Five of these markers-D2S408 (2q36), D6S271 (6p21),
      D6S344 (6p25), D7S1818 (7p12) and D16S420 (16p12)-remained nominally significant
      in both studies after conservative refining analysis.

PMID- 14575929
TI  - A genomic screen of Spanish multiple sclerosis patients reveals multiple loci
      associated with the disease.
AB  - In order to identify the genomic regions that might confer susceptibility to
      multiple sclerosis (MS) in the Spanish population, we have performed a genome
      wide screen for association in patients with MS using pooled DNA from 200
      clinical cases and 200 healthy controls. The pools were typed using 5546
      microsatellites. The typing was repeated for the most promising 1269 markers
      after which 191 potentially associated markers were identified. Eleven of these
      markers map to the MHC region, and 14 to non-MHC regions identified in previous
      linkage screens. Our results provide support for the presence of multiple coding
      regions that contain MS susceptibility genes of small or moderate effect.

PMID- 14575930
TI  - A genome screen for linkage disequilibrium in Turkish multiple sclerosis.
AB  - In order to screen the Turkish population for evidence of association with
      multiple sclerosis, we typed 6000 microsatellite markers in separately pooled DNA
      samples from 197 cases and 199 controls following the Genetic Analysis of
      Multiple sclerosis in EuropeanS (GAMES) protocol. Twelve markers showing evidence
      for association were identified. One of these markers lying directly in a region
      which is also implicated in the Turkish linkage screen (chromosome 5p15) and thus
      shows evidence for both linkage and association in independent data sets.

PMID- 14575932
TI  - Variations of acidic functions at position 2 and substituents at positions 4, 5
      and 6 of the indole moiety and their effect on NMDA-glycine site affinity.
AB  - The synthetic procedures to obtain indole derivatives with different acidic
      functions at position 2 of the indole are reported. The synthesised and tested
      derivatives comprise 5-tetrazolyl, 1,3,4-oxadiazol-5-yl-2-one, and indole-2
      carboxylic acid amides with 5-aminotetrazole, methanesulphonamide and
      trifluoromethanesulphonamide moieties. The binding affinity was evaluated using
      [3H]MDL 105,519 and pig cortical brain membranes. In general, compounds with
      acidic functions different from a carboxylic acid moiety are less potent than
      indole-2-carboxylic acid derivatives. Also, the 4,6-dichloro substitution pattern
      was compared to 5-tert-butyl derivatives and compounds not substituted in the
      benzene moiety of the indole, indicating that the affinity increases from 5-tert
      butyl over unsubstituted to 4,6-dichloro substituted derivatives.

PMID- 14575933
TI  - A quantitative structure-activity relationship study on a novel class of calcium
      entry blockers: 1-[(4-(aminoalkoxy)phenyl)sulphonyl]indolizines.
AB  - A quantitative structure-activity relationship (QSAR) study has been made on two
      different series of 1-[(4-(aminoalkoxy)phenyl)sulphonyl]indolizines acting as
      calcium entry blockers, using some physicochemical and structural parameters. Two
      different assays were reported for both the series: (IC(50))(A), referring to the
      molar concentration of the compound required to reduce [3H] nitrendipine binding
      by 50%, and (IC(50))(B), referring to that required to block Ca(2+) induced
      concentration of K(+) depolarised rat aorta by 50%. For series 1, where the 2
      position substituents of indolizine ring were varied along with the aminoalkoxy
      moieties of the phenyl ring, the QSAR analysis shows that the 2-position
      substituents can equally affect both the activities through their hydrophobic and
      electronic properties and the aminoalkoxy moiety through some steric effects. For
      series 2, where the indolizine ring has been replaced by varying heterocyclic
      rings, along with the changes in aminoalkoxy moiety of the phenyl ring, the QSAR
      exhibits that these different heterocyclic rings affect both the activities
      through some steric roles, altering the conformations of the receptors from
      system A to system B. Among the different heterocyclic rings, the N-substituted
      indole ring is shown to be more conducive to both the activities than any other
      ring. However, a 5-membered ring is indicated to be less effective than a 9- or
      10-membered ring for activity B. Additionally, the amino moieties having phenyl
      ring with methoxy groups at 3,4,and 5-positions are shown to favour both A and B
      activities.

PMID- 14575934
TI  - Synthesis and investigation of antimicrobial activity of some bisbenzimidazole
      derived chelating agents.
AB  - The 1,2-bis(2-benzimidazyl)-1,2-ethanediol (1), 1,4-bis(2-benzimidazyl)-1,2,3,4
      butanetetraol (2), 1,3-bis(2-benzimidazyl)-2-thiapropane (3), 1,3-bis(2
      benzimidazyl)-2-thia-propane-dihydrochloride (4), 1,5-bis(2-benzimidazyl)-3
      thiapentane (5), and 1,5-bis(2-benzimidazyl)-3-thiapentane dihydrochloride (6)
      chelating ligands are synthesised and characterised by using analytical data and
      modem spectroscopic methods such as FT-Raman, FT-IR, 1H- and 13C-NMR
      spectrometers. Their antimicrobial activities are reported by comparing the in
      vitro activities, with those of ofloxacin, ciprofloxacin, piperacillin,
      ampicillin and cefazolin antibacterial agents against fresh clinical isolates.
      Antifungal activities are reported on Candida albicans, Candida utilis,
      Cryptococcus neoformans fungi, and the results are referenced with amphotericin
      B, fluconazole and flucytosine antifungal agents. It has been found that all the
      compounds have broad spectra activity and was either more active or equipotent to
      those compared antibiotic and antifungal agents.

PMID- 14575935
TI  - Synthesis and biological evaluation of S-acyl-3-thiopropyl prodrugs of N
      phosphonoacetyl-L-aspartate (PALA).
AB  - The synthesis of new prodrugs of PALA characterised by the presence of S-acyl-3
      thiopropyl, as enzyme-labile groups on the phosphonate moiety of PALA, is
      reported. The cytotoxic activities of PALA prodrugs were determined against human
      cell line (SW1573 lung carcinoma cells). A number of prodrugs bearing S-pivaloyl
      as acyl groups displayed cytotoxic activity in the same order of magnitude of
      PALA.

PMID- 14575936
TI  - Synthesis, characterization and biological properties of a novel copper complex.
AB  - The study of copper complex in relation to cancer is important in many ways. A
      novel copper complex has been synthesized with non toxic ligand, viz. potassium
      salt of N-(2-hydroxy acetophenone) glycinate (NHAG). The structure of the complex
      has been determined by spectroscopic means. Toxicity and antitumor property of
      the complex has been studied in vivo. Though the complex is toxic at higher
      doses, lower non toxic doses of the complex deplete glutathione (GSH). GSH
      depleting property of the complex may be utilized to sensitize drug resistant
      cells where resistance is due to elevated level of GSH.

PMID- 14575937
TI  - Synthesis, cytotoxicity and antiviral activity of podophyllotoxin analogues
      modified in the E-ring.
AB  - Several podophyllotoxin derivatives modified in the E-ring were prepared and
      evaluated for their cytotoxicity on four neoplastic cell lines (P-388, A-549, HT
      29 and MEL-28) and for their antiherpetic activity against Herpes simplex virus
      type II. The trimethoxyphenyl moiety was oxidized to ortho-quinone and further
      condensed with diamines and enamines to form different heterocycles. Most of the
      compounds maintained their cytotoxicity at the muM level and some of them showed
      antiherpetic activity.

PMID- 14575938
TI  - Implementation of the Women's Health Initiative study design.

PMID- 14575939
TI  - The Women's Health Initiative recruitment methods and results.

PMID- 14575940
TI  - The Women's Health Initiative postmenopausal hormone trials: overview and
      baseline characteristics of participants.

PMID- 14575941
TI  - The Women's Health Initiative Dietary Modification trial: overview and baseline
      characteristics of participants.

PMID- 14575942
TI  - The Women's Health Initiative calcium-vitamin D trial: overview and baseline
      characteristics of participants.

PMID- 14575943
TI  - The Women's Health Initiative Observational Study: baseline characteristics of
      participants and reliability of baseline measures.

PMID- 14575944
TI  - Outcomes ascertainment and adjudication methods in the Women's Health Initiative.

PMID- 14575945
TI  - Biodiesel production from waste cooking oil: 2. Economic assessment and
      sensitivity analysis.
AB  - The economic feasibilities of four continuous processes to produce biodiesel,
      including both alkali- and acid-catalyzed processes, using waste cooking oil and
      the 'standard' process using virgin vegetable oil as the raw material, were
      assessed. Although the alkali-catalyzed process using virgin vegetable oil had
      the lowest fixed capital cost, the acid-catalyzed process using waste cooking oil
      was more economically feasible overall, providing a lower total manufacturing
      cost, a more attractive after-tax rate of return and a lower biodiesel break-even
      price. On the basis of these economic calculations, sensitivity analyses for
      these processes were carried out. Plant capacity and prices of feedstock oils and
      biodiesel were found to be the most significant factors affecting the economic
      viability of biodiesel manufacture.

PMID- 14575946
TI  - Pyrolysis of plant, animal and human waste: physical and chemical
      characterization of the pyrolytic products.
AB  - Pyrolysis (carbonization) has been proposed as one of several optional
      technologies for disposing and recycling waste products in Japan. Plant wastes
      (sugarcane bagasse and rice husks), animal waste (cow biosolids) and human waste
      (treated municipal sludge) were pyrolyzed at temperatures from 250-800 degrees C
      in closed containers. The carbonized materials were evaluated for specific
      physical properties (yield, surface area, density) and specific chemical
      properties (total carbon, total nitrogen, pH, fixed carbon, ash content,
      volatility) in order to compare differences in properties among the four waste
      products. The results indicated that (1) surface area, total carbon, ash content
      and pH increased as the carbonization temperature increased, while carbonization
      yield decreased with increasing temperature, (2) product density however was not
      affected by temperature and (3) correlation coefficients were determined among
      the physical and chemical properties and several significant correlations were
      observed. The data indicate that source material had considerable influence on
      the physical and chemical properties of the carbonized products.

PMID- 14575947
TI  - Protein size distribution and inhibitory effect of wheat hydrolysates on
      Neutrase.
AB  - Neutrase, used for hydrolysis of wheat proteins, was inhibited by end-product in
      a competitive uncompetitive way. The inhibition ratio depends on the progress of
      protein hydrolysis (degree of hydrolysis) and it remains constant beyond a degree
      of hydrolysis of 7.5%. The inhibitor was separated, on Sephadex G-25 column, in
      three fractions (>2.4, 2.4-0.5 and <0.5 kDa) generating an inhibition ratio of
      29%, 46% and 67% respectively. The peptides size distribution (<1, 1-2, 2-3 and
      >3 kDa) of fractions was determined using size exclusion-high performance liquid
      chromatography. The analysis of obtained data, using a simple mathematical
      regression, showed a correlation factor of 0.98 between the inhibition ratio and
      the peptides less than 1 kDa and 0.99 when considering the peptides lower than 1
      kDa and higher than 3 kDa.

PMID- 14575948
TI  - Cocoa shells for heavy metal removal from acidic solutions.
AB  - The development of economic and efficient processes for the removal of heavy
      metals present in acidic effluents from industrial sources or decontamination
      technologies has become a priority. The purpose of this work was to study the
      efficiency with which cocoa shells remove heavy metals from acidic solutions (pH
      2) and to investigate how the composition of these solutions influences heavy
      metal uptake efficiency. Adsorption tests were conducted in agitated flasks with
      single-metal solutions (0.25 mM Al, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb and Zn), multi
      metal solution (comprised of 0.25 mM of each of the cations above) and an
      effluent obtained from chemical leaching of metal-contaminated soil, in the
      presence of different cocoa shell concentrations (5-40 g/l). Results from the
      single-metal solution assays indicated that the fixation capacity of heavy metals
      by cocoa shells followed a specific order: Pb>Cr>Cd=Cu=Fe>Zn=Co>Mn=Ni=Al. Cocoa
      shells are particularly efficient in the removal of lead from very acidic
      solutions (q(max)=6.2 mg Pb/g, pH(i)=2.0 and T=22 degrees C). The presence of
      other metals and cations in solution did not seem to affect the recovery of lead.
      It was also observed that the maximum metal uptake was reached in less than 2 h.
      This research has also demonstrated that the removal of metals caused a decline
      in solution proton concentration (pH increase) and release of calcium, magnesium,
      potassium and sodium from the cocoa shells.

PMID- 14575949
TI  - De-icers derived from corn steep water.
AB  - Corn steep water (CSW) and other byproducts derived from fermentations and sugar
      productions are presently forming the base of compositions for de-icing and anti
      icing materials. Since the de-icing and anti-icing values are in part a
      colligative property, increase in the molar concentration of ionic species has
      been frequently necessary to decrease further the freezing point of this
      byproducts stream. In the present study this has been achieved by the generation
      of biodegradable organic acid salts in situ, without the use of chloride or other
      inorganic salts, by the alkaline degradation of reducing sugars added to corn
      steep water, which alone is not an efficient de-icer. Reducing sugars, such as
      glucose, react with alkali metal hydroxides to produce principally hydroxy
      carboxylic acids that react with the alkali metal hydroxide to form a mixture of
      organic acid salts. The ionic strength of the resulting solution is increased
      since each sugar molecule produces nearly two acid molecules upon degradation.
      The ionic strength necessary to achieve the desired freezing point depression is
      determined by the amount and concentration of the alkali metal hydroxide used,
      with the necessary counter anions being derived from the degradation of the
      reducing sugar. The amount of the sugar used is that required to result in a near
      to neutral final solution. The well-known anti-corrosive property of CSW is used
      in the de-icer preparations, either by conducting the alkaline degradation of the
      sugar in this medium, or by using water for the degradation of the sugar followed
      by dilution of the resulting solution with CSW to adjust the viscosity of the
      final solution to meet the requirements for spraying. The monovalent metal
      hydroxides are more efficient in producing de-icer solutions than the divalent
      metal hydroxides.

PMID- 14575950
TI  - Effect of fly ash, organic wastes and chemical fertilizers on yield, nutrient
      uptake, heavy metal content and residual fertility in a rice-mustard cropping
      sequence under acid lateritic soils.
AB  - A field experiment was conducted for two years in sandy loam acid lateritic soil
      to study the direct effect of fly ash, organic wastes and chemical fertilizers on
      rice (Oryza sativa) and their residual effect on mustard (Brassica napus var
      glauca) grown in sequence. Rice yields were higher when fly ash, organic wastes
      and chemical fertilizers were used in an integrated manner as compared to sole
      application of chemical fertilizers. Yields of mustard were also higher under the
      residual effect of the former rather than the latter. However, this beneficial
      residual effect under integrated nutrient sources was inadequate for the mustard
      crop in the low fertility test soil. Hence, direct application of fertilizers was
      needed, in addition to residual fertility. The effect of fly ash on mean rice
      equivalent yield of the rice-mustard cropping sequence was highest (up to 14%)
      when it was used in combination with organic wastes and chemical fertilizers.
      While the yield increase was 10% when it was used in combination with only
      chemical fertilizers. The minimum yield advantage, 3%, occurred when fly ash was
      applied alone. The equivalent yield of the rice-mustard cropping sequence was
      equally influenced by either of the organic wastes. Cadmium and Ni content in
      rice grain and straw were less under the direct effect of fly ash. The residual
      effect on mustard was similar for Ni content in seed and stover; however, Cd
      content was increased. Beneficial residual soil chemical properties in terms of
      pH, organic carbon and available N, P and K were noted for integrated nutrient
      treatments involved fly ash, organic wastes and chemical fertilizers as compared
      to continuous use of only chemical fertilizers. Application of fly ash alone was
      effective in raising soil available P. Thus, integrated use of fly ash, organic
      wastes and chemical fertilizers was beneficial in improving crop yield, soil pH,
      organic carbon and available N, P and K in sandy loam acid lateritic soil.

PMID- 14575951
TI  - Intermittent drying of bioproducts--an overview.
AB  - Unlike the conventional practice of supplying energy for batch drying processes
      at a constant rate, newly developed intermittent drying processes employ time
      varying heat input tailored to match the drying kinetics of the material being
      dried. The energy required may be supplied by combining different modes of heat
      transfer (e.g. convection coupled with conduction or radiation or dielectric
      heating simultaneously or in a pre-selected sequence) in a time-varying fashion
      so as to provide optimal drying kinetics as well as quality of the bioproduct.
      This is especially important for drying of heat-sensitive materials (such as
      foods, pharmaceutical, neutraceutical substances, herbs, spices and herbal
      medicines). Intermittent heat supply is beneficial only for materials which dry
      primarily in the falling rate period where internal diffusion of heat and
      moisture controls the overall drying rate. Periods when little or no heat is
      supplied for drying allow the tempering period needed for the moisture and heat
      to diffuse within the material. As the moisture content increases at the surface
      of the biomaterial during the tempering period, the rate of drying is higher when
      heat input is resumed. It is possible to control the heat input such that the
      surface temperature of the product does not exceed a pre-determined value beyond
      which thermal damage of the material may occur. This process results in reduction
      in the use of thermal energy as well as the mass of air used in convective
      drying. Thus, the thermal efficiency of such a process is higher. The quality of
      the product, as such color and ascorbic acid content, is also typically superior
      to that obtained with a continuous supply of heat. However, in some cases, there
      will be a nominal increase in drying time. In the case of microwave-assisted and
      heat pump drying, for example, the capital cost of the drying system can also be
      reduced by drying in the intermittent mode. This paper provides an overview of
      the basic process, selected results from experiments and mathematical models for
      a variety of biomaterials dried in a wide assortment of dryers. It begins with a
      classification of intermittent drying processes that may be applied e.g. time
      varying temperature, air flow rate, operating pressure as well as heat input by
      different modes and in different temporal variations. The beneficial effects of
      improving the quality of dried bioproducts by different intermittent processes
      are also included and discussed.

PMID- 14575952
TI  - Synthesis of alkyl-alpha-L-rhamnosides by water soluble alcohols enzymatic
      glycosylation.
AB  - The synthesis of alkyl-alpha-rhamnosides by alpha-rhamnosidase was studied using
      rhamnose and rhamnosides, particularly the flavonoid naringin, as glycosylation
      agents, and water soluble alcohols as acceptors. The reaction products were
      analyzed by HPLC chromatography and identified by 13C y 1H NMR. The glycosylation
      of alcohols by reverse hydrolysis was maximum for 40% methanol, 30% ethanol, 10%
      propanol and 20% isopropanol. Under optimum conditions the yield of rhamnose to
      alkyl-alpha-rhamnoside transformation decreased from 68% for methyl-alpha
      rhamnoside to 10% for isopropyl-alpha-rhamnoside. The time course of
      rhamnosylations produced using naringin as the donor was comparable with that of
      the reverse hydrolysis obtained at the same molar concentration of the donor. The
      flavonoids and their derivatives remaining in the solution after the
      glycosylation were removed by ion exchange QEAE chromatography at pH 10. These
      results indicate that both, reverse hydrolysis and glycosylation by naringin are
      acceptable procedures for the enzymatic synthesis of short chain length alkyl
      alpha-L-rhamnosides.

PMID- 14575953
TI  - An image method to evaluate bagasse fiber dimensions.
AB  - In the last 25 years the amount of textile nonwovens used for industrial and
      commercial applications increased more than 10 times. Bagasse fiber, a by-product
      from sugar cane industry, provides a natural resource for nonwoven industries.
      Even though underrated as a potential fiber, bagasse comes more and more into
      attention because of the increasing concern for disposal of agricultural
      residuals and the need for enhancing the sugar cane industry's profitability.
      However, there is a lack of an instrumental method to evaluate bagasse fiber
      length and fineness. This paper presents a study on measuring the bagasse
      fineness using image analysis method. Cross-sections images of bagasse fibers
      were visualized using Scanning Electronic Microscopy (SEM). The computing
      software Scion Image was used to measure bagasse fiber length and cross-sectional
      area. Relationship between fiber fineness and cross-sectional area was analyzed
      using the statistical method of regression.

PMID- 14575954
TI  - Vermicomposting of mixed solid textile mill sludge and cow dung with the epigeic
      earthworm Eisenia foetida.
AB  - This paper reports the results of a study of vermicomposting with Eisenia foetida
      of solid textile mill sludge mixed with cow dung in different ratios in a 90 days
      composting experiment. Vermicomposting resulted in significant reduction in C:N
      ratio and increase in TKN. Total K and Ca were lower in the final cast than the
      initial feed mixture. Microbial activity measured as dehydrogenase activity
      increased up to 75 days and decreased on further incubation. Total P was higher
      in the final product than the initial feed mixture. Total heavy metal contents
      were lower in the final product than initial feed mixture. Solid textile mill
      sludge can be potentially useful as raw substrate in vermicomposting if mixed
      with up to 30% cow dung (on dry weight basis). The growth and cocoon production
      of the worm species in different feed mixtures were also investigated.

PMID- 14575955
TI  - Productive performance of broiler chicks fed diets containing irradiated meat
      bone meal.
AB  - Experiments were carried out to study the changes in the values of feed
      efficiency (FE), total protein efficiency (TPE) and metabolizable energy
      efficiency (MEE) of broiler chicks fed during four age periods (14-21, 21-28, 28
      35 and 35-42 days). Five experimental diets were similar in composition but
      different in the irradiation dose (0, 5, 10, 25 or 50 kGy) applied to the meat
      bone meal content of each diet. The results indicated that feeding of broiler
      chicks on irradiated meat-bone meal (5-50 kGy) had no significant (P>0.05)
      effects on FE, TPE, MEE and body weight gain during the four experimental age
      periods. The average values of the FE (feed consumption/weight gain), TPE (weight
      gain/total protein consumption) and MEE (metabolizable energy consumption in
      MJ/kg gain) were 1.96, 2.59 and 23.13, respectively. The values of FE and MEE
      increased while TPE decreased significantly (P<0.05) with age. The pooled FE
      value was 1.60 during the 14-21 days of age and increased to 2.66 from 35-42 days
      of age. However, the TPE value was 3.01 during the 14-21-day age period and
      decreased to 1.82 over the 35-42-day age period. The energy consumption value to
      produce one kg of body weight increased during the 35-42-day period by 7.71-12.72
      MJ/kg gain in comparison with that from the other experimental age periods.
      Weight gain rate decreased significantly (P<0.05) during the 35-42-day period (66
      g/week/bird) when compared with the rate observed during the 14 through 35-day
      age period.

PMID- 14575956
TI  - Reductive dechlorination of 2-chlorophenol in a hydrogenotrophic, gas-permeable,
      silicone membrane bioreactor.
AB  - A gas-permeable silicone membrane bioreactor was used to cultivate the biofilm
      under hydrogenotrophic condition for reductive dechlorination of 2-chlorophenol
      (2-CP). The anaerobic sludge obtained from a swine wastewater treatment plant was
      immobilized by polyvinyl alcohol (PVA) so as to form a biofilm on the surface of
      the silicone tube. After acclimating for about 4 months, the bioreactor showed a
      high dechlorinating performance. Under the condition of continuous feeding with 2
      CP at 25 mg/l and the hydraulic retention time of 15 h, the 2-CP removal
      efficiency reached 92.8% (2-CP decay rate: 0.67 g/m(2)d of surface area of
      silicone tube). H(2) was used as electron donor for dechlorinating 2-CP, and
      produced the dechlorinating intermediate, phenol. Both nitrate and sulfate played
      important roles in inhibiting 2-CP dechlorination through different biological
      mechanisms. Nitrate can be easily utilized as an electron acceptor by the
      biofilm, while sulfate cannot. Results of this study demonstrated that nitrate
      competed with 2-CP as the electron acceptor, while sulfate retarded the activity
      of hydrogen-dechlorinating bacteria and thus inhibited the 2-CP dechlorination.

PMID- 14575958
TI  - Development of a modified vermireactor for efficient vermicomposting: a
      laboratory study.
AB  - Waste has become an index of growth. Utilization of waste materials for
      productivity purposes is important for both economic and environmental reasons.
      Vermicomposting is an important aspect as it converts waste to wealth. In this
      context, a modified vermireactor in place of the conventional vermireactor for
      efficient vermicomposting has been developed. In the conventional low- and high
      rate vermireactors, the space for vermicomposting is reduced due to the thick
      layer of vermibed at the bottom of the reactor, thus a small amount of worm casts
      is produced. In the modified vermireactors there was only a thick moist cloth at
      the bottom in place of the thick vermibed which allowed a comparatively large
      quantity of organic waste to be vermicomposted as compared to conventional
      vermireactors. Laboratory studies showed that the modified vermireactor performed
      better than the conventional vermireactor in average vermicast produced and mg
      castings l(-1) (digester volume) day(-1). The study further showed that only the
      volume of the vermireactor was responsible for the high yield of worm casts.

PMID- 14575957
TI  - Effects of season on the yield and quality of agar from Gracilaria species
      (Gracilariaceae, Rhodophyta).
AB  - The effect of season on yield and physical properties of agars extracted from
      Gracia gracilis and G. bursa-pastoris were determined. The agar yield from G.
      gracilis was maximum during spring (30%) and minimum during autumn (19%). In G.
      bursa-pastoris, the agar yield was greatest in summer (36%) and lowest in winter
      (23%). Agar yield from G. bursa-pastoris was positively correlated with
      temperature (r=0.94; P<0.01) and salinity (r=0.97; P<0.01) and negatively with
      nitrogen content (r=-0.93; P<0.01). Agar gel strengths fluctuated from 229 to 828
      gcm(-2) and 23 to 168 gcm(-2) for G. gracilis and G. bursa-pastoris,
      respectively. The gelling temperature showed significant seasonal variation for
      both species. Chemical analysis of agar from the two seaweeds indicated variation
      in 3,6-anhydrogalactose and sulfate content (P<0.01). Furthermore, there was an
      inverse correlation between the two chemical variables. In general, agar
      extracted from G. gracilis possessed better qualities than agar extracted from G.
      bursa-pastoris and can be considered a candidate for industrial use.

PMID- 14575959
TI  - Recovery of lignin and furfural from acetic acid-water-HCl pulping liquors.
AB  - The feasibility of the HCl-water-acetic acid pulping technology (Acetosolv
      process) depends on the efficiency of solvent and byproduct recovery.
      Experimental data and computer simulation calculations are presented to assess
      these points. The recovery of precipitable, dissolved solids derived from lignin
      by mixing pulping liquors and water in various proportions was studied. Computer
      simulation of selected operational strategies enabling the recovery of furfural
      from the liquors obtained in the lignin-precipitation stage are also presented.

PMID- 14575960
TI  - The use of chemically modified and unmodified cassava waste for the removal of
      Cd, Cu and Zn ions from aqueous solution.
AB  - The use of different chemically modified cassava waste biomass for the
      enhancement of the adsorption of three metal ions Cd, Cu and Zn from aqueous
      solution is reported in this paper. Treating with different concentrations of
      thioglycollic acid modified the cassava waste biomass. The sorption rates of the
      three metals were 0.2303 min(-1) (Cd(2+)), 0.0051 min(-1) (Cu(2+)), 0.0040 min(
      1) (Zn(2+)) and 0.109 min(-1) (Cd(2+)), 0.0069 min(-1) (Cu(2+)), 0.0367 min(-1)
      (Zn(2+)) for 0.5 and 1.00 M chemically modified levels, respectively. The
      adsorption rates were quite rapid and within 20-30 min of mixing, about 60-80% of
      these ions were removed from the solutions by the biomass and that chemically
      modifying the binding groups in the biomass enhanced its adsorption capacity
      towards the three metals. The results further showed that increased concentration
      of modifying reagent led to increased incorporation, or availability of more
      binding groups, in the biomass matrix, resulting in improved adsorptivity of the
      cassava waste biomass. The binding capacity study showed that the cassava waste,
      which is a serious environmental nuisance, due to foul odour released during
      decomposition, has the ability to adsorb trace metals from solutions.

PMID- 14575961
TI  - Biosorption of mercury from aqueous solution by Ulva lactuca biomass.
AB  - The mercury biosorption onto non-living protonated biomass of Ulva lactuca, as an
      alternative method for mercury removal from aqueous solutions, was investigated.
      Batch equilibrium tests showed that at pH 3.5, 5.5 and 7 the maxima of mercury
      uptake values, according to Langmuir adsorption isotherm, were 27.24, 84.74 and
      149.25 mg/g, respectively. The ability of Ulva lactuca biomass to adsorb mercury
      in fixed-bed column, was investigated as well. The influence of column bed
      height, flow rate and effluent initial concentration of metal was studied. The
      adsorbed metal ions were easily desorbed from the algal biomass with 0.3 N
      H(2)SO(4) solution. After acid desorption and regeneration with distilled water,
      the biomass could be reused for other biosorption assays with similar
      performances.

PMID- 14575962
TI  - Act now to secure Iraq's health.

PMID- 14575963
TI  - Supporting decisions in clinical medicine: neural networks in lower
      gastrointestinal haemorrhage.

PMID- 14575964
TI  - Cooking the waste.

PMID- 14575965
TI  - Percutaneous transcoronary venous access for cellular cardiomyoplasty.

PMID- 14575966
TI  - Insulin and cognitive function.

PMID- 14575967
TI  - Fulvestrant: spreading the word, but not too thinly.

PMID- 14575968
TI  - Erythropoietin to treat head and neck cancer patients with anaemia undergoing
      radiotherapy: randomised, double-blind, placebo-controlled trial.
AB  - BACKGROUND: Anaemia is associated with poor cancer control, particularly in
      patients undergoing radiotherapy. We investigated whether anaemia correction with
      epoetin beta could improve outcome of curative radiotherapy among patients with
      head and neck cancer. METHODS: We did a multicentre, double-blind, randomised,
      placebo-controlled trial in 351 patients (haemoglobin <120 g/L in women or <130
      g/L in men) with carcinoma of the oral cavity, oropharynx, hypopharynx, or
      larynx. Patients received curative radiotherapy at 60 Gy for completely (R0) and
      histologically incomplete (R1) resected disease, or 70 Gy for macroscopically
      incompletely resected (R2) advanced disease (T3, T4, or nodal involvement) or for
      primary definitive treatment. All patients were assigned to subcutaneous placebo
      (n=171) or epoetin beta 300 IU/kg (n=180) three times weekly, from 10-14 days
      before and continuing throughout radiotherapy. The primary endpoint was
      locoregional progression-free survival. We assessed also time to locoregional
      progression and survival. Analysis was by intention to treat. FINDINGS: 148 (82%)
      patients given epoetin beta achieved haemoglobin concentrations higher than 140
      g/L (women) or 150 g/L (men) compared with 26 (15%) given placebo. However,
      locoregional progression-free survival was poorer with epoetin beta than with
      placebo (adjusted relative risk 1.62 [95% CI 1.22-2.14]; p=0.0008). For
      locoregional progression the relative risk was 1.69 (1.16-2.47, p=0.007) and for
      survival was 1.39 (1.05-1.84, p=0.02). INTERPRETATION: Epoetin beta corrects
      anaemia but does not improve cancer control or survival. Disease control might
      even be impaired. Patients receiving curative cancer treatment and given
      erythropoietin should be studied in carefully controlled trials.

PMID- 14575969
TI  - Prediction of outcome in acute lower-gastrointestinal haemorrhage based on an
      artificial neural network: internal and external validation of a predictive
      model.
AB  - BACKGROUND: Models based on artificial neural networks (ANN) are useful in
      predicting outcome of various disorders. There is currently no useful predictive
      model for risk assessment in acute lower-gastrointestinal haemorrhage. We
      investigated whether ANN models using information available during triage could
      predict clinical outcome in patients with this disorder. METHODS: ANN and
      multiple-logistic-regression (MLR) models were constructed from non-endoscopic
      data of patients admitted with acute lower-gastrointestinal haemorrhage. The
      performance of ANN in classifying patients into high-risk and low-risk groups was
      compared with that of another validated scoring system (BLEED), with the outcome
      variables recurrent bleeding, death, and therapeutic interventions for control of
      haemorrhage. The ANN models were trained with data from patients admitted to the
      primary institution during the first 12 months (n=120) and then internally
      validated with data from patients admitted to the same institution during the
      next 6 months (n=70). The ANN models were then externally validated and direct
      comparison made with MLR in patients admitted to an independent institution in
      another US state (n=142). FINDINGS: Clinical features were similar for training
      and validation groups. The predictive accuracy of ANN was significantly better
      than that of BLEED (predictive accuracy in internal validation group for death
      87% vs 21%; for recurrent bleeding 89% vs 41%; and for intervention 96% vs 46%)
      and similar to MLR. During external validation, ANN performed well in predicting
      death (97%), recurrent bleeding (93%), and need for intervention (94%), and it
      was superior to MLR (70%, 73%, and 70%, respectively). INTERPRETATION: ANN can
      accurately predict the outcome for patients presenting with acute lower
      gastrointestinal haemorrhage and may be generally useful for the risk
      stratification of these patients.

PMID- 14575970
TI  - Retroperitoneal paraganglioma.

PMID- 14575971
TI  - Determinants of survival following HIV-1 seroconversion after the introduction of
      HAART.
AB  - BACKGROUND: Highly active antiretroviral therapy (HAART) was introduced in 1997.
      We aimed to assess the continuing effect of this treatment on survival and
      progression to AIDS after HIV-1 seroconversion. METHODS: We used Cox models to
      estimate the effect of calendar year on time to AIDS and death in 22 cohorts of
      people from Europe, Australia, and Canada who had seroconverted. Retrospective
      and prospective data were used. We compared the effects of age at seroconversion,
      exposure category, sex, and presentation during acute HIV-1 infection pre-1997
      (pre-HAART), in 1997-98 (limited use of HAART), and 1999-2001 (widespread use of
      HAART). FINDINGS: Of 7740 seroconverters, 2000 (26%) had died. Compared with pre
      1997 data, the hazard ratio (HR) for death fell sharply to 0.47 [95% CI 0.39
      0.56] in 1997, dropping further to 0.16 [0.12-0.22] in 2001. Correspondingly, the
      proportion of person-time on HAART increased from 22% in 1997 to 57% in 2001. By
      contrast with the pre-HAART era, injecting drug users had significantly higher
      mortality in 1999-2001 than did men infected through sex with men (HR 4.28 [2.86
      6.41]). However, whereas pre-1997 the risk of AIDS was higher in those aged 45
      years or older at seroconversion than in people who were 16-24 years (2.03 [1.67
      2.47]), in 1999-2001 there was little evidence of a difference in risk by age
      (HR=1.17 [0.60-2.30]; interaction p=0.06). No such attenuation in the effect of
      age on survival was observed (p=0.63). INTERPRETATION: Predicted survival for
      people with HIV-1 has continued to increase, since the introduction of HAART;
      however, the importance of age and exposure category as determinants of
      progression seems to have changed.

PMID- 14575973
TI  - Occam's razor; anaemia and orthostatic hypotension.

PMID- 14575972
TI  - Genetic cause of hyperglycaemia and response to treatment in diabetes.
AB  - BACKGROUND: Type 2 diabetes shows evidence of underlying heterogeneity. No
      studies have assessed whether different causes for diabetes change the response
      to oral hypoglycaemic therapy. In a few cases, patients with diabetes caused by
      mutations in the hepatocyte nuclear factor 1alpha (HNF-1alpha) gene have been
      described as sensitive to the hypoglycaemic effects of sulphonylureas. We aimed
      to see whether the glycaemic response to the sulphonylurea gliclazide and the
      biguanide metformin differed in HNF-1alpha diabetes and type 2 diabetes, and to
      investigate the mechanism for differences in sulphonylurea sensitivity. METHODS:
      We did a randomised crossover trial of glicazide and metformin in 36 patients,
      either with diabetes caused by HNF-1alpha mutations or type 2 diabetes, who were
      matched for body-mass index and fasting plasma glucose. The primary outcome was
      reduction in fasting plasma glucose. Analysis was by intention to treat. We
      assessed possible mechanisms for sulphonylurea sensitivity through insulin
      sensitivity, insulin secretory response to glucose and tolbutamide, and
      tolbutamide clearance. FINDINGS: Patients with HNF-1alpha diabetes had a 5.2-fold
      greater response to gliclazide than to metformin (fasting plasma glucose
      reduction 4.7 vs 0.9 mmol/L, p=0.0007) and 3.9-fold greater response to
      gliclazide than those with type 2 diabetes (p=0.002). Patients with HNF-1alpha
      diabetes had a strong insulin secretory response to intravenous tolbutamide
      despite a small response to intravenous glucose, and were more insulin sensitive
      than those with type 2 diabetes. Sulphonylurea metabolism was similar in both
      patient groups. INTERPRETATION: The cause of hyperglycaemia changes the response
      to hypoglycaemic drugs; HNF-1alpha diabetes has marked sulphonylurea sensitivity.
      This pharmacogenetic effect is consistent with models of HNF-1alpha deficiency,
      which show that the beta-cell defect is upstream of the sulphonylurea receptor.
      Definition of the genetic basis of hyperglycaemia has implications for patient
      management.

PMID- 14575974
TI  - A newly identified tick-borne Borrelia species and relapsing fever in Tanzania.
AB  - Tick-borne relapsing fever caused by the spirochaete Borrelia duttonii is a
      common cause of serious illness in central Tanzania. Screening of Ornithodoros sp
      ticks from infested houses for the presence of B duttonii had detected a
      previously unidentified species of Borrelia. We investigated whether this species
      infected the human population in a central Tanzanian village, by use of blood
      slide examination and PCR. PCR was twice as sensitive in detection of infections,
      showing Borrelia sp in six (11%) of 54 children with fever, and in 13 (4%) of 307
      otherwise healthy children. Genotyping Borrelia from 17 infections identified
      Borrelia duttonii and an unnamed species. Our findings show that the newly
      discovered species is a causal agent of tick-borne relapsing fever.

PMID- 14575975
TI  - Solar disinfection of infectious biomedical waste: a new approach for developing
      countries.
AB  - Poor developing countries cannot afford expensive technologies such as
      incineration for management of infectious biomedical waste. We assessed solar
      heating as an alternative technology. We immersed simulated infectious waste with
      added challenge bacteria in water in a box-type solar cooker, which was left in
      the sun for 6 h. In 24 sets of observations, the amount of viable bacteria was
      reduced by about 7 log. We also tested infectious medical waste with a heavy load
      of bacteria (10(8)-10(9)/g) from our hospital's burn unit for solar heat
      disinfection in 20 experiments. Our results showed a similar 7 log reduction in
      the amount of viable bacteria. Solar heating thus seems to be a cheap method to
      disinfect infectious medical waste in less economically developed countries.

PMID- 14575976
TI  - Echinococcosis.
AB  - Echinococcosis is a near-cosmopolitan zoonosis caused by adult or larval stages
      of cestodes belonging to the genus Echinococcus (family Taeniidae). The two major
      species of medical and public health importance are Echinococcus granulosus and
      Echinococcus multilocularis, which cause cystic echinococcosis and alveolar
      echinococcosis, respectively. Both are serious and severe diseases, the latter
      especially so, with high fatality rates and poor prognosis if managed
      incorrectly. Several reports have shown that both diseases are of increasing
      public health concern and that both can be regarded as emerging or re-emerging
      diseases. In this review we discuss aspects of the biology, life cycle,
      aetiology, distribution, and transmission of the Echinococcus organisms, and the
      epidemiology, clinical features, treatment, and diagnosis of the diseases they
      cause. We also discuss the countermeasures available for the control and
      prevention of these diseases. E granulosus still has a wide geographical
      distribution, although effective control against cystic echinococcosis has been
      achieved in some regions. E multilocularis and alveolar echinococcosis are more
      problematic, since the primary transmission cycle is almost always sylvatic so
      that efficient and cost-effective methods for control are unavailable.

PMID- 14575977
TI  - Clinical update on adults with congenital heart disease.
AB  - The number of patients with congenital cardiac disease reaching adulthood is
      increasing steadily. Many adults with such disease face both medical and surgical
      difficulties. Most clinicians know very little about basic cardiac defects, their
      natural history, complications after surgery, and adequate management of these
      patients. We aim to provide an overview of the most frequently encountered
      cardiac lesions and long-term complications and to outline an up-to-date approach
      to their management. We present a series of hypothetical cases and discuss their
      management.

PMID- 14575978
TI  - Sources of error: from procedures to end-of-life decisions.

PMID- 14575979
TI  - The need for research in primary care.
AB  - Making evidence from scientific studies available to clinical practice has been
      expected to directly improve quality of care, but this expectation has not been
      realised. The notion of quality of care is complex, and quality improvement needs
      medical, contextual, and policy evidence. In primary care, research is needed
      that takes into account the specific characteristics of its population and the
      presentation and prevalence of illness and disease. The context of the doctor
      patient encounter plays a major part, and needs better understanding. At the
      policy level, issues of equity must be addressed. The knowledge base for family
      practice must be expanded by integration of multiple methods of comprehension, so
      we can bridge the gap between evidence and practice.

PMID- 14575980
TI  - Intravenous fluids for seriously ill children: time to reconsider.

PMID- 14575981
TI  - Doctors in conflict.

PMID- 14575982
TI  - Doctors in conflict.

PMID- 14575983
TI  - Doctors in conflict.

PMID- 14575984
TI  - Breast cancer and hormone-replacement therapy: the Million Women Study.

PMID- 14575985
TI  - Breast cancer and hormone-replacement therapy: the Million Women Study.

PMID- 14575986
TI  - Doctors in conflict.

PMID- 14575987
TI  - Breast cancer and hormone-replacement therapy: the Million Women Study.

PMID- 14575988
TI  - Breast cancer and hormone-replacement therapy: the Million Women Study.

PMID- 14575989
TI  - Breast cancer and hormone-replacement therapy: the Million Women Study.

PMID- 14575990
TI  - Breast cancer and hormone-replacement therapy: the Million Women Study.

PMID- 14575992
TI  - Breast cancer and hormone-replacement therapy: the Million Women Study.

PMID- 14575993
TI  - Breast cancer and hormone-replacement therapy: the Million Women Study.

PMID- 14575995
TI  - Nanoscience debate.

PMID- 14575996
TI  - ICON4/AGO-OVAR-2.2: questions about trial design, cost-effectiveness, and
      clinical benefit.

PMID- 14575997
TI  - ICON4/AGO-OVAR-2.2: questions about trial design, cost-effectiveness, and
      clinical benefit.

PMID- 14575998
TI  - ICON4/AGO-OVAR-2.2: questions about trial design, cost-effectiveness, and
      clinical benefit.

PMID- 14576000
TI  - Is there a solution to organ commerce in non-directed donors?

PMID- 14576001
TI  - Doctors from the Indian subcontinent and UK general practice.

PMID- 14576002
TI  - Gender composition of editorial boards of general medical journals.

PMID- 14576006
TI  - Polypharmacy.

PMID- 14576008
TI  - Hemochromatosis: when blood is too iron-rich.

PMID- 14576009
TI  - Antidepressants protect brain from depression-related shrinkage.

PMID- 14576010
TI  - Partial-breast irradiation: Less may be more.

PMID- 14576011
TI  - News about flu vaccines.

PMID- 14576012
TI  - By the way, doctor. Most of your hormone articles are about Premarin, made from
      the urine of pregnant horses, combined with Provera, an artificial progesterone.
      My pharmacist compounds a natural cream for me, using hormones identical to mine,
      and I swear by it. What's your opinion?

PMID- 14576013
TI  - By the way, doctor. I've read that hair analysis can tell me a lot about my
      health. Is this true?

PMID- 14576014
TI  - Preventing prostate cancer with finasteride: a mixed blessing.

PMID- 14576015
TI  - Preventing strokes: understanding stroke and evaluating your risk. The first of
      two parts.

PMID- 14576016
TI  - Medical memo. What do Americans eat?

PMID- 14576017
TI  - On call. When my wife was in the hospital with a kidney infection four years ago,
      her doctor came in to see her every day, but when I caught pneumonia this year,
      my doctor turned me over to a hospital doctor until I got home. I did get good
      care, but I missed seeing my regular M.D. What do you think of this way of doing
      things?

PMID- 14576018
TI  - Beyond shyness and stage fright: social anxiety disorder.

PMID- 14576019
TI  - Cognitive behavioral therapy for schizophrenia.

PMID- 14576020
TI  - Preventing aggression in children.

PMID- 14576021
TI  - Dementia and a diagnostic dilemma.

PMID- 14576022
TI  - Questions & answers. The physical, emotional, and family problems of people with
      anorexia nervosa are pretty well-known. Do people with this disorder have
      problems with their intellectual functioning?

PMID- 14576023
TI  - Are you too old to donate? Maybe not. As the waiting list for transplants gets
      longer, older and living donors are more welcome.

PMID- 14576024
TI  - Dental implants: when teeth go missing.

PMID- 14576025
TI  - Healing the open wound. Chronic wounds are a formula for frustration--and worse.
      New drugs and treatments might help. So do the basics, like keeping them clean
      and free of infection.

PMID- 14576026
TI  - Osteopenia: when you have weak bones, but not osteoporosis. Treatment for low
      bone density depends on how strong your bones are--not the name of the disease.

PMID- 14576027
TI  - Beer: mind over fatter.

PMID- 14576028
TI  - Smoking ban: don't have a heart attack about it.

PMID- 14576029
TI  - Six tips to keep you on your feet.

PMID- 14576030
TI  - By the way, doctor. Can you help me out? I've been taking warfarin (Coumadin) for
      two years now because of a deep-vein thrombus that broke off and went to my
      lungs. I'd like to get off it. I've also had a hard time managing my vitamin K
      levels and have been told to cut back on fruits and vegetables.

PMID- 14576031
TI  - By the way, doctor. After a recent blood pressure check, my doctor bumped up my
      dose of Lotensin [an ACE inhibitor] from 10 milligrams to 20. I had been taking
      the 10-mg pill in the morning, but my doctor advised me to take the new, higher
      dose in the evening. He said most strokes and heart attacks happen in the
      morning, and that I could get better protection by taking the drug right before.
      But I read in the Health Letter a couple of months ago that you recommend morning
      intake, so I am confused.

PMID- 14576032
TI  - When playing the numbers is a sure bet. It pays to know your cholesterol levels
      and some other key markers of heart health.

PMID- 14576033
TI  - Eating to lower cholesterol.

PMID- 14576034
TI  - Living with amiodarone. The story behind this effective heart-rhythm drug, the
      way it acts in the body, and even its side effects are on the strange side.
      Understanding its idiosyncrasies can help you use it safely.

PMID- 14576035
TI  - Let the butt stop here. Any time is the right time to stop smoking. A host of
      stop-smoking aids can boost your odds of success.

PMID- 14576036
TI  - Imaging advances. Tools that help doctors "see" inside the blood vessels may help
      prevent heart attacks.

PMID- 14576037
TI  - Healthy eating gets nutty.

PMID- 14576038
TI  - Even a little exercise helps blood pressure.

PMID- 14576039
TI  - Ask the doctor. I am a 64-year-old woman with high cholesterol caused by bad
      genes (familial hypercholesterolemia). Without medication, my cholesterol is
      above 450 mg/dL. So I am taking high-dose Lipitor (80 mg/day), WelChol, and Zetia
      to lower my cholesterol. I sometimes have pain and stiffness in my knees, and my
      shoulder, elbow, and wrist joints, plus the muscles in between, are stiff in the
      morning and hurt during the day. Two years ago I was diagnosed with bursitis in
      my hips. Could these problems be from the Lipitor? If so, is there another statin
      I could take that wouldn't do this?

PMID- 14576040
TI  - Ask the doctor. I am a 50-year-old man with congestive heart failure. My doctor
      has me on all the usual drugs, and a couple of years ago added spironolactone. I
      did okay with it for a while, but then began to notice that my breasts were
      getting bigger and began to hurt. My doctor agreed that I should stop taking
      spironolactone, but I wonder if I am missing out on something.

PMID- 14576041
TI  - Chronic active Epstein-Barr virus infection associated with mutations in perforin
      that impair its maturation.
AB  - Chronic active Epstein-Barr virus infection (CAEBV) is a rare disease in which
      previously healthy persons develop severe, life-threatening illness. Mutations in
      the perforin gene have been found in familial hemophagocytic lymphohistiocytosis,
      which shares some features with CAEBV. We studied a patient who died at age 18,
      10 years after the onset of CAEBV. The patient had high titers of antibodies to
      EBV, EBV RNA in lymph nodes, T-cell lymphoproliferative disease, and
      hemophagocytic lymphohistiocytosis. DNA sequencing showed novel mutations in both
      alleles of the perforin gene that resulted in amino acid changes in the protein.
      The quantity of the native form of perforin from the patient's stimulated
      peripheral blood mononuclear cells (PBMCs) was extremely low and immunoblotting
      showed accumulation of an uncleaved precursor form of perforin. Stimulated PBMCs
      from the patient were defective for Fas-independent cytotoxicity. These data
      imply that mutations in this patient resulted in reduced perforin-mediated
      cytotoxicity by his lymphocytes. This is the first case in which perforin
      mutations have been shown to result in accumulation of the uncleaved, immature
      form of perforin. Mutations in the perforin gene are associated with some cases
      of CAEBV with hemophagocytic lymphohistiocytosis.

PMID- 14576042
TI  - Identification of a 4-base deletion in the gene in inherited intrinsic factor
      deficiency.
AB  - A 4-base deletion has been identified in the coding region of the gene for
      gastric intrinsic factor (IF) in an 11-year-old girl with severe anemia and
      cobalamin (Cbl) deficiency. The bone marrow showed frank megaloblastic
      morphology, and the Schilling test indicated a failure to absorb Cbl that was
      corrected by coadministration of IF. Pentagastrin administration induced acid
      secretion, but the gastric juice lacked IF as determined by CbI binding, by
      fractionation of protein-bound CbI, and by immunoprecipitation with anti-IF
      antiserum. Individual exons were amplified by the polymerase chain reaction by
      using primers to the flanking intronic regions, and the nucleotide sequence
      analysis identified a 4-base deletion (c183_186delGAAT) spanning positions 104 to
      107 in exon 2, resulting in premature termination of translation. This mutation
      also eliminates a site for Bst XI endonuclease and introduces a site for BsaBI
      for identifying this deletion in hereditary IF deficiency.

PMID- 14576043
TI  - Prognosis at diagnosis: integrating molecular biologic insights into clinical
      practice for patients with CLL.
AB  - Heterogeneity in the clinical behavior of patients with chronic lymphocytic
      leukemia (CLL) makes it difficult for physicians to accurately identify which
      patients may benefit from an early or more aggressive treatment strategy and to
      provide patients with relevant prognostic information. Given the potential
      efficacy of newer therapies and the desire to treat patients at "optimum" times,
      it is more important than ever to develop sensitive stratification parameters to
      identify patients with poor prognosis. The evolution of risk stratification
      models has advanced from clinical staging and use of basic laboratory parameters
      to include relevant biologic and genetic features. This article will review the
      dramatic progress in prognostication for CLL and will propose statistical
      modeling techniques to evaluate the utility of these new measures in predictive
      models to help determine the optimal combination of markers to improve
      prognostication for individual patients. This discussion will also elaborate
      which markers and tools should be used in current clinical practice and evaluated
      in ongoing clinical trials.

PMID- 14576044
TI  - Novel concatameric heparin-binding peptides reverse heparin and low-molecular
      weight heparin anticoagulant activities in patient plasma in vitro and in rats in
      vivo.
AB  - Patients given unfractionated heparin (UFH) or low-molecular-weight heparin
      (LMWH) for prophylaxis or treatment of thrombosis sometimes suffer serious
      bleeding. We showed previously that peptides containing 3 or more tandem repeats
      of heparin-binding consensus sequences have high affinity for LMWH and neutralize
      LMWH (enoxaparin) in vivo in rats and in vitro in citrate. We have now modified
      the (ARKKAAKA)(n) tandem repeat peptides by cyclization or by inclusion of
      hydrophobic tails or cysteines to promote multimerization. These peptides exhibit
      high-affinity binding to LMWH (dissociation constant [K(d)], approximately 50
      nM), similar potencies in neutralizing anti-Factor Xa activity of UFH and
      enoxaparin added to normal plasma in vitro, and efficacy equivalent to or greater
      than protamine. Peptide (ARKKAAKA)(3)VLVLVLVL was most effective in all plasmas
      from enoxaparin-treated patients, and was 4- to 20-fold more effective than
      protamine. Several other peptide structures were effective in some patients'
      plasmas. All high-affinity peptides reversed inhibition of thrombin-induced clot
      formation by UFH. These peptides (1 mg/300 g rat) neutralized 1 U/mL anti-Factor
      Xa activity of enoxaparin in rats within 1 to 2 minutes. Direct blood pressure
      and heart rate measurements showed little or no hemodynamic effect. These heparin
      binding peptides, singly or in combination, are potential candidates for clinical
      reversal of UFH and LMWH in humans.

PMID- 14576046
TI  - Ineffective hematopoiesis linked with a mitochondrial tRNA mutation (G3242A) in a
      patient with myelodysplastic syndrome.
AB  - In a patient with refractory anemia with excess blasts (RAEB), a somatic mutation
      of mitochondrial transfer RNA(Leu(UUR)) was detected in bone marrow cells.
      Heteroduplex analysis indicated that 40% to 50% of mitochondrial DNA (mtDNA)
      molecules in the bone marrow (BM) carried the novel G3242A mutation. The
      proportion of mutant mtDNA was higher in CD34(+) cells than in the unfractionated
      sample. Surprisingly, the mutation was not detectable by heteroduplex analysis in
      the peripheral blood (PB). However, PB CD34(+) cells selected by immunomagnetic
      beads harbored the mutation with a proportion of approximately 50%. In
      hematopoietic colony assays, CD34(+) cells from BM and PB yielded only colonies
      with wild-type mtDNA. These results indicate that the mtDNA mutation in CD34(+)
      cells was associated with a maturation defect. Mitochondrial tRNA mutations
      impair mitochondrial protein synthesis, thereby causing dysfunction of the
      mitochondrial respiratory chain. We propose that this effect contributed to
      ineffective hematopoiesis in our patient.

PMID- 14576045
TI  - Identification of the molecular requirements for an RAR alpha-mediated cell cycle
      arrest during granulocytic differentiation.
AB  - Retinoids are potent inducers of cell cycle arrest and differentiation of
      numerous cell types, notably granulocytes. However the mechanisms by which
      retinoids mediate cell cycle arrest during differentiation remain unclear. We
      have used myeloid differentiation to characterize the molecular pathways that
      couple cell cycle withdrawal to terminal differentiation. Using primary cells
      from mice deficient for either the cyclin-dependent kinase inhibitor (CDKi)
      p27(Kip1), the Myc antagonist Mad1, or both Mad1 and p27(Kip1), we observed that
      signals mediated through retinoic acid receptor alpha (RAR alpha), but not RAR
      beta or gamma, required both Mad1 and p27(Kip1) to induce cell cycle arrest and
      to accelerate terminal differentiation of granulocytes. Although RAR alpha did
      not directly regulate Mad1 or p27(Kip1), the RAR alpha target gene C/EBP epsilon
      directly regulated transcription of Mad1. Induction of C/EBP epsilon activity in
      granulocytic cells led to rapid induction of Mad1 protein and transcript, with
      direct binding of C/EBP epsilon to the Mad1 promoter demonstrated through
      chromatin immunoprecipitation assay. These data demonstrate that cell cycle
      arrest in response to RAR alpha specifically requires Mad1 and p27(Kip1) and that
      Mad1 is transcriptionally activated by CCAAT/enhancer-binding protein epsilon
      (C/EBP epsilon). Moreover, these data demonstrate selectivity among the RARs for
      cell cycle arrest pathways and provide a direct mechanism to link differentiation
      induction and regulation of the Myc antagonist Mad1.

PMID- 14576047
TI  - Risk-adapted treatment of acute promyelocytic leukemia with all-trans-retinoic
      acid and anthracycline monochemotherapy: a multicenter study by the PETHEMA
      group.
AB  - All-trans-retinoic acid (ATRA) increases the efficacy of chemotherapy when used
      for induction and maintenance treatment of acute promyelocytic leukemia (APL),
      but its role in consolidation is unknown. Since November 1996, 426 patients with
      newly diagnosed APL have received induction therapy with ATRA and idarubicin.
      Before November 1999 (LPA96 study), consolidation therapy consisted of 3 courses
      of anthracycline monochemotherapy. After November 1999 (LPA99 study), patients
      with intermediate and high risks of relapse received consolidation therapy with
      ATRA and increased doses of anthracyclines. Of the 384 patients who achieved
      complete remission (90%), 382 proceeded to consolidation therapy. Seven patients
      died in remission (1.8%). The 3-year cumulative incidence of relapse for patients
      in the LPA96 and LPA99 studies was 17.2% and 7.5%, respectively (P =.008).
      Patients treated with ATRA in consolidation therapy showed an overall reduction
      in the relapse rate from 20.1% to 8.7% (P =.004). In intermediate-risk patients
      the rate decreased from 14.0% to 2.5% (P =.006). This improved antileukemic
      efficacy also translated into significantly better disease-free and overall
      survival. A risk-adapted strategy combining anthracycline monochemotherapy and
      ATRA for induction and consolidation therapy of newly diagnosed APL results in
      improved antileukemic efficacy and a high degree of compliance.

PMID- 14576048
TI  - A haplotype of the EPCR gene is associated with increased plasma levels of sEPCR
      and is a candidate risk factor for thrombosis.
AB  - The endothelial cell protein C (PC) receptor (EPCR) facilitates PC activation by
      the thrombin-thrombomodulin complex. A soluble form of this receptor (sEPCR)
      found in plasma inhibits both activated PC (aPC) activity and PC activation by
      competing for PC with membrane-associated EPCR. Elevated sEPCR levels are found
      in approximately 20% of healthy subjects, but the mechanisms underlying this
      interindividual variability are unknown. We measured sEPCR levels in 100 healthy
      male volunteers, and observed 2 phenotypic groups of subjects. The temporal
      stability of sEPCR levels suggested genetic control. Extensive analysis of the
      EPCR gene in these subjects revealed 13 polymorphisms in complete linkage
      disequilibrium; these defined 3 haplotypes, 1 of which (A3) was strongly
      associated with high sEPCR levels. The high constitutive sEPCR levels observed in
      A3 haplotype carriers might reduce the efficiency of the PC system and predispose
      these subjects to venous thrombosis. By studying 338 patients with venous
      thrombosis and 338 age- and sex-matched healthy subjects, we found that the A3
      haplotype was overrepresented in the patients. In multivariate analysis, subjects
      carrying the A3 haplotype had an increased risk of thrombosis (odds ratio [OR] =
      1.8; P =.004). Thus, the A3 haplotype, which is associated with elevated plasma
      sEPCR levels, is a candidate risk factor for venous thrombosis.

PMID- 14576049
TI  - DC-SIGN promotes exogenous MHC-I-restricted HIV-1 antigen presentation.
AB  - Dendritic cells (DCs) facilitate HIV-1 spread in the host by capturing virions
      and transferring them to permissive lymphocytes in lymphoid organs. Lectins such
      as DC-specific ICAM-grabbing non-integrin (DC-SIGN) are involved in HIV-1 uptake
      by DCs, through high-affinity binding to viral envelope glycoproteins. We
      examined the role of DC-SIGN on the fate of incoming virions and on major
      histocompatibility complex class I (MHC-I)-restricted HIV-1 antigen presentation.
      We show that DC-SIGN expression in B-cell lines dramatically enhances viral
      internalization. In these cells, and also in primary DCs, most of the captured
      virions are rapidly degraded, likely in a lysosomal compartment. In addition, a
      fraction of incoming viral material is processed by the proteasome, leading to
      activation of anti-HIV-specific cytotoxic T lymphocytes (CTLs) by DC-SIGN
      expressing cells. In DCs, DC-SIGN is not the only receptor involved, and
      redundant pathways of virus capture leading to antigen presentation likely
      coexist. Altogether, our results highlight new aspects of DC-SIGN interactions
      with HIV-1. The lectin does not significantly protect captured virions against
      degradation and promotes MHC-I exogenous presentation of HIV-1 antigens.

PMID- 14576050
TI  - Specific inhibition of HIV-1 coreceptor activity by synthetic peptides
      corresponding to the predicted extracellular loops of CCR5.
AB  - We used synthetic peptides to the extracellular loops (ECLs) of CCR5 to examine
      inhibitory effects on HIV infection/fusion with primary leukocytes and cells
      expressing recombinant CCR5. We show for the first time that peptides derived
      from the first, second, or third ECL caused dose-dependent inhibition of fusion
      and infection, although with varying potencies and specificities for envelope
      glycoproteins (Envs) from different strains. The first and third ECL peptides
      inhibited Envs from the R5 Ba-L strain and the R5X4 89.6 strain, whereas the
      second ECL peptide inhibited Ba-L but not 89.6 Env. None of the peptides affected
      fusion mediated by Env from the X4 LAV strain. Fusion mediated by Envs from
      several primary HIV-1 isolates was also inhibited by the peptides. These findings
      suggest that various HIV-1 strains use CCR5 domains in different ways.
      Experiments involving peptide pretreatment and washing, modulation of the
      expression levels of Env and CCR5, analysis of CCR5 peptide effects against
      different coreceptors, and inhibition of radiolabeled glycoprotein (gp) 120
      binding to CCR5 suggested that the peptide-blocking activities reflect their
      interactions with gp120. The CCR5-derived ECL peptides thus provide a useful
      approach to analyze structure-function relationships involved in HIV-1 Env
      coreceptor interactions and may have implications for the design of drugs that
      inhibit HIV infection.

PMID- 14576051
TI  - Suppression of in vitro megakaryocyte production by antiplatelet autoantibodies
      from adult patients with chronic ITP.
AB  - Chronic immune thrombocytopenic purpura (ITP) is manifested by autoantibody
      induced platelet destruction. Platelet turnover studies suggest that autoantibody
      may also affect platelet production. To evaluate this, we studied the effect of
      plasma from adult patients with chronic ITP on in vitro megakaryocyte production.
      CD34(+) cells, obtained from healthy donors, were cultured in medium containing
      PEG-rHuMGDF and 10% plasma from either ITP patients or healthy subjects. Cultures
      containing plasma from 12 of 18 ITP patients showed a significant decrease (26%
      95%) in megakaryocyte production when compared with control cultures. Positive
      ITP plasmas not only reduced the total number of megakaryocytes produced during
      the culture period but also inhibited megakaryocyte maturation, resulting in
      fewer 4N, 8N, and 16N cells. The role of antibody in this suppression is
      supported by 2 factors: (1) immunoglobulin G (IgG) from ITP patients inhibited
      megakaryocyte production when compared with control IgG; and (2) adsorption of
      autoantibody, using immobilized antigen, resulted in significantly less
      inhibition of megakaryocyte production when compared with unadsorbed plasma.
      These results show that plasma autoantibody from some adult patients with ITP
      inhibits in vitro megakaryocyte production, suggesting that a similar effect may
      occur in vivo.

PMID- 14576052
TI  - The functional cobalamin (vitamin B12)-intrinsic factor receptor is a novel
      complex of cubilin and amnionless.
AB  - Imerslund-Grasbeck syndrome (I-GS, megaloblastic anemia 1) is an autosomal
      recessive disorder characterized by intestinal cobalamin (vitamin B(12))
      malabsorption and proteinuria. I-GS-causing mutations are found in either of 2
      genes encoding the epithelial proteins: cubilin and amnionless (AMN). Cubilin
      recognizes intrinsic factor (IF)-cobalamin and various other proteins to be
      endocytosed in the intestine and kidney, respectively, whereas the function of
      AMN is unknown. Here we show that cubilin and AMN colocalize in the endocytic
      apparatus of polarized epithelial cells and copurify as a tight complex during IF
      cobalamin affinity and nondenaturing gel filtration chromatography. In
      transfected cells expressing either AMN or a truncated IF-cobalamin-binding
      cubilin construct, neither protein alone conferred ligand endocytosis. In cubilin
      transfectants, cubilin accumulated in early biosynthetic compartments. However,
      in cells cotransfected with AMN and the cubilin construct, cubilin trafficked to
      the cell surface and endosomes, and the cells exhibited IF-cobalamin endocytosis
      and lysosomal degradation of IF. These data indicate that cubilin and AMN are
      subunits of a novel cubilin/AMN (cubam) complex, where AMN binds to the amino
      terminal third of cubilin and directs subcellular localization and endocytosis of
      cubilin with its ligand. Therefore, mutations affecting either of the 2 proteins
      may abrogate function of the cubam complex and cause IG-S.

PMID- 14576053
TI  - Endothelial progenitor cells in infantile hemangioma.
AB  - Infantile hemangioma is an endothelial tumor that grows rapidly after birth but
      slowly regresses during early childhood. Initial proliferation of hemangioma is
      characterized by clonal expansion of endothelial cells (ECs) and
      neovascularization. Here, we demonstrated mRNA encoding CD133-2, an important
      marker for endothelial progenitor cells (EPCs), predominantly in proliferating
      but not involuting or involuted hemangioma. Progenitor cells coexpressing CD133
      and CD34 were detected by flow cytometry in 11 of 12 proliferating hemangioma
      specimens from children 3 to 24 months of age. Furthermore, in 4 proliferating
      hemangiomas, we showed that 0.14% to 1.6% of CD45(-) nucleated cells were EPCs
      that coexpressed CD133 and the EC marker KDR. This finding is consistent with the
      presence of KDR(+) immature ECs in proliferating hemangioma. Our results suggest
      that EPCs contribute to the early growth of hemangioma. To our knowledge, this is
      the first study to show direct evidence of EPCs in a human vascular tumor.

PMID- 14576054
TI  - Role of tissue factor and protease-activated receptors in a mouse model of
      endotoxemia.
AB  - Sepsis is associated with a systemic activation of coagulation and an excessive
      inflammatory response. Anticoagulants have been shown to inhibit both coagulation
      and inflammation in sepsis. In this study, we used both genetic and pharmacologic
      approaches to analyze the role of tissue factor and protease-activated receptors
      in coagulation and inflammation in a mouse endotoxemia model. We used mice
      expressing low levels of the procoagulant molecule, tissue factor (TF), to
      analyze the effects of TF deficiency either in all tissues or selectively in
      hematopoietic cells. Low TF mice had reduced coagulation, inflammation, and
      mortality compared with control mice. Similarly, a deficiency of TF expression by
      hematopoietic cells reduced lipopolysaccharide (LPS)-induced coagulation,
      inflammation, and mortality. Inhibition of the down-stream coagulation protease,
      thrombin, reduced fibrin deposition and prolonged survival without affecting
      inflammation. Deficiency of either protease activated receptor-1 (PAR-1) or
      protease activated receptor-2 (PAR-2) alone did not affect inflammation or
      survival. However, a combination of thrombin inhibition and PAR-2 deficiency
      reduced inflammation and mortality. These data demonstrate that hematopoietic
      cells are the major pathologic site of TF expression during endotoxemia and
      suggest that multiple protease-activated receptors mediate crosstalk between
      coagulation and inflammation.

PMID- 14576055
TI  - Deletion of the alpha-globin gene cluster as a cause of acquired alpha
      thalassemia in myelodysplastic syndrome.
AB  - Rarely, myelodysplastic syndrome (MDS) is complicated by an acquired form of
      alpha-thalassemia (alpha-thalassemia in myelodysplastic syndrome [ATMDS])
      characterized by hypochromic, microcytic, anisopoikilocytic red blood cells with
      hemoglobin H (HbH) inclusions. Acquired mutations in ATRX, a chromatin remodeling
      gene, have recently been found in 12 patients with typical features of ATMDS,
      though they have not been detected in MDS patients with similar red blood cell
      findings but little HbH. The alpha-globin genes themselves have appeared normal
      in all ATMDS patients studied to date. Here we characterize the molecular defect
      in a unique MDS patient with rare HbH inclusions in which an abnormal clone lost
      a greater than 1.9-Mb segment of the telomeric region of the short arm of one
      allele of chromosome 16, including both alpha-globin genes. Red blood cell
      changes associated with this acquired somatic genotype (--/alpha alpha) are
      surprisingly severe, demonstrating that a minor globin chain imbalance may be
      unexpectedly deleterious during the abnormal erythropoiesis that occurs in the
      context of MDS.

PMID- 14576056
TI  - BUBR1 deficiency results in abnormal megakaryopoiesis.
AB  - The physiologic function of BUBR1, a key component of the spindle checkpoint, was
      examined by generating BUBR1-mutant mice. BUBR1(-/-) embryos failed to survive
      beyond day 8.5 in utero as a result of extensive apoptosis. Whereas BUBR1(+/-)
      blastocysts grew relatively normally in vitro, BUBR1(-/-) blastocysts exhibited
      impaired proliferation and atrophied. Adult BUBR1(+/-) mice manifested
      splenomegaly and abnormal megakaryopoiesis. BUBR1 haploinsufficiency resulted in
      an increase in the number of splenic megakaryocytes, which was correlated with an
      increase in megakaryocytic, but a decrease in erythroid, progenitors in bone
      marrow cells. RNA interference-mediated down-regulation of BUBR1 also caused an
      increase in polyploidy formation in murine embryonic fibroblast cells and
      enhanced megakaryopoiesis in bone marrow progenitor cells. However, enhanced
      megakaryopoiesis in BUBR1(+/-) mice was not correlated with a significant
      increase in platelets in peripheral blood, which was at least partly due to a
      defect in the formation of proplatelet-producing megakaryocytes. Together, these
      results indicate that BUBR1 is essential for early embryonic development and
      normal hematopoiesis.

PMID- 14576057
TI  - Chemokine receptor-8 (CCR8) mediates human vascular smooth muscle cell chemotaxis
      and metalloproteinase-2 secretion.
AB  - The response of the arterial vascular wall to injury is characterized by vascular
      smooth muscle cell (VSMC) migration, a process requiring metalloproteinase
      production. This migration is induced by cytokines, however the agonists involved
      are not fully defined. The CC chemokine receptor 8 (CCR8) is expressed on
      monocytes and T lymphocytes and is the sole receptor for the human CC chemokine 1
      (CCL1, I-309) and for the viral chemokine, vCCL1 (viral macrophage inflammatory
      protein 1 [vMIP-1]). We have reported that CCR8 is expressed on human umbilical
      vein endothelial cells (HUVECs) and mediates chemotaxis induced by CCL1. The
      conditioned medium from incubation mixtures of lipoprotein(a) (Lp(a)) and HUVECs
      (LCM) contained CCL1 and stimulated both monocyte and HUVEC chemotaxis, providing
      novel mechanisms for the atherogenicity of Lp(a). We now report that CCL1, vCCL1,
      and LCM stimulate chemotaxis of human VSMCs that is blocked by murine monoclonal
      antibody against CCR8 and by the G-protein inhibitor pertussis toxin. The effect
      of anti-CCR8 was specific, as this antibody failed to effect the chemotaxis of
      VSMCs in response to CCL3 or by platelet-derived growth factor BB (PDGF-BB).
      VSMCs contained CCR8 mRNA and CCR8 antigen coprecipitated with VSMC membranes.
      Antibodies against metalloproteinase-2 (MMP-2) inhibited the CCL1-induced
      chemotaxis of VSMCs, whereas anti-MMP-9 was less effective. CCL1 induced VSMC pro
      MMP-2 mRNA and protein secretion. Poxvirus MC148 inhibited the increase in MMP-2
      induced by CCL1, documenting that CCR8 was the receptor responsible. In mouse
      femoral arteries, CCR8 and TCA3 antigen colocalized with VSMCs and were up
      regulated after injury. The induction of CCR8 and CCL1/TCA3 under conditions
      associated with VSMC proliferation and migration raises the possibility that CCR8
      may play an important role in vessel wall pathology.

PMID- 14576058
TI  - Early prediction of response in patients with relapsed or refractory Philadelphia
      chromosome-positive acute lymphoblastic leukemia (Ph+ALL) treated with imatinib.
AB  - Imatinib has pronounced but brief antileukemic activity in advanced Philadelphia
      chromosome-positive acute lymphoblastic leukemia (Ph(+)ALL). We assessed the
      prognostic impact of pretreatment disease features and the early bone marrow (BM)
      response in 68 consecutive patients with Ph(+)ALL receiving imatinib salvage
      therapy. A complete hematologic or marrow response was achieved by 92% of
      patients with BM blasts below 5% on day 14, whereas 62.5% of patients with more
      than 5% BM blasts on day 14 were nonresponders. Similarly, time to progression
      (TTP) was superior in patients with a good day 14 response (5.2 versus 0.9
      months; P <.0001). Prior complete remission of less than 6 months, white blood
      cell count of more than 10 x 10(9)/L, circulating peripheral blood blasts at
      diagnosis, additional Philadelphia chromosomes, or at least 2 Bcr-Abl fusion
      signals were associated with significantly inferior remission rate and response
      duration. In patients without poor prognostic features, single-agent imatinib may
      be appropriate before transplant salvage therapy. Conversely, patients with
      clinically or cytogenetically defined poor-risk features are candidates for
      trials of upfront imatinib in combination with other agents.

PMID- 14576059
TI  - CXCR4 engagement is required for HIV-1-induced L-selectin shedding.
AB  - The chemokine receptor, CXCR4, serves as the primary coreceptor for entry of T
      cell tropic human immunodeficiency virus (HIV). Binding of either the CXC
      chemokine, stromal-derived factor 1 alpha (SDF-1 alpha), or a CXCR4 antagonist,
      AMD3100, to CXCR4 inhibits infection of CD4(+) T cells by T-tropic HIV-1,
      although only SDF-1 alpha triggers T-cell signaling cascades. We have previously
      demonstrated that ligation of CD4 by T-cell tropic HIV-1 NL4-3 induces
      metalloproteinase-dependent L-selectin (CD62L) shedding on resting CD4(+) T
      cells. However, the role of CXCR4 in HIV-induced L-selectin shedding is unclear.
      Here, we show that L-selectin shedding induced by HIV-1 NL4-3 is completely
      reversed by AMD3100, but not SDF-1 alpha, although SDF-1 alpha alone does not
      induce L-selectin shedding. These results indicate that engagement of both CD4
      and CXCR4 is required for HIV-induced shedding of L-selectin on primary resting
      CD4(+) T cells.

PMID- 14576060
TI  - Second cancers and late toxicities after treatment of aggressive non-Hodgkin
      lymphoma with the ACVBP regimen: a GELA cohort study on 2837 patients.
AB  - The survival of patients with aggressive non-Hodgkin lymphoma (NHL) is
      increasing, but the incidence of secondary cancer and late toxicity is poorly
      defined for those treated with cyclophosphamide-hydroxydaunomycin/doxorubicin
      Oncovin-prednisone (CHOP)-like chemotherapy. From February 1984 to January 1998,
      2837 patients with aggressive NHL received the control-arm chemotherapy
      adriamycin-cyclophosphamide-vindesine-bleomycin-prednisone (ACVBP) in 3
      consecutive Groupe d'Etude des Lymphomes de l'Adulte (GELA) studies. With a
      median follow-up time of 74 months, the 5-year overall and event-free survival
      rates were 60% and 52%. Two hundred two occurrences of nonneoplastic late
      toxicity were reported, resulting in a 5.35% cumulative probability of incidence
      at 7 years. Eighty-one second tumors developed, for which the 7-year cumulative
      incidence rate was 2.75%; 64 were solid tumors, and 17 were hematologic
      malignancies. In multivariate analysis, age was the only risk factor for the
      second development of cancer. Epidemiologic analysis allowed a comparison of this
      NHL group with the general population. Considering all tumors, no excess of
      second cancer was observed. In the male population, however, there was an excess
      of lung cancer (standardized incidence ratio [SIR], 2.45; P <.001) and
      myelodysplastic syndrome/acute myelocytic leukemia (MDS/AML) (SIR, 5.65; P
      =.006), and in the female population there was an excess of MDS/AML (SIR, 19.9; P
      <.001). With a long follow-up, the ACVBP regimen was highly effective for the
      treatment of aggressive NHL. Increases occurred in secondary MDS/AML and in lung
      cancer among men.

PMID- 14576061
TI  - A T-cell epitope encoded by a subset of HLA-DPB1 alleles determines nonpermissive
      mismatches for hematologic stem cell transplantation.
AB  - The importance of HLA-DPB1 matching for the outcome of allogeneic hematologic
      stem cell (HSC) transplantation is controversial. We have previously identified
      HLA-DPB1*0901 as a target of cytotoxic T cells mediating in vivo rejection of an
      HSC allograft. Here we show that HLA-DPB1*0901 encodes a T-cell epitope shared by
      a subset of DPB1 alleles that determines nonpermissive mismatches for HSC
      transplantation. Several T-cell clones obtained from the patient at the time of
      rejection showed HLA-DP restricted recognition of allogeneic targets expressing
      HLA-DPB1*0901, *1001, *1701, *0301, *1401, and *4501, but not other alleles.
      Based on these findings, we developed an algorithm for prediction of
      nonpermissive HLA-DPB1 mismatches. Retrospective evaluation of 118
      transplantations showed that the presence of nonpermissive HLA-DPB1 mismatches
      was correlated with significantly increased hazards of acute grade II to IV graft
      versus-host disease (HR = 1.87, P =.046) and transplantation-related mortality
      (HR = 2.69, P =.027) but not relapse (HR = 0.98, P =.939), as compared with the
      permissive group. There was also a marked but statistically not significant
      increase in the hazards of overall mortality (HR = 1.64, P =.1). These data
      suggest that biologic characterization of in vivo alloreactivity can be a tool
      for definition of clinically relevant nonpermissive HLA mismatches for unrelated
      HSC transplantation.

PMID- 14576063
TI  - Dose-escalated donor lymphocyte infusions following reduced intensity
      transplantation: toxicity, chimerism, and disease responses.
AB  - Data on the application of donor lymphocyte infusions (DLIs) following reduced
      intensity transplantation (RIT) remain limited. Persistence of host antigen
      presenting cells might increase the efficacy or toxicity of cellular
      immunotherapies. We report the results of dose-escalating DLIs in 46 patients
      undergoing RIT, who received a total of 109 infusions to treat mixed chimerism or
      residual or progressive disease. Diagnoses were myeloma (n = 19), Hodgkin
      lymphoma (n = 13), non-Hodgkin lymphoma (n = 10), and other (n = 4). Thirty-two
      had an HLA-matched family donor and 14 an unrelated donor. Grades II to IV graft
      versus-host disease (GVHD) occurred in 5 sibling and 7 unrelated donor
      recipients. GVHD was more common (P =.002), occurred at lower T-cell doses, and
      was more severe in the unrelated donor cohort. Conversion from mixed to
      multilineage full donor chimerism occurred in 30 of 35 evaluable patients.
      Presence of mixed chimerism in the granulocyte lineage at the time of DLI did not
      predict for chimerism response or GVHD. Disease responses occurred in 63% of
      patients with myeloma and 70% of those with Hodgkin lymphoma and were not
      predicted by changes in chimerism. These data support the presence of clinically
      relevant graft-versus-Hodgkin activity and indicate that DLI may be associated
      with a significantly increased toxicity in unrelated compared to sibling donor
      transplant recipients receiving identical treatment protocols.

PMID- 14576062
TI  - An inhibitor of the EGF receptor family blocks myeloma cell growth factor
      activity of HB-EGF and potentiates dexamethasone or anti-IL-6 antibody-induced
      apoptosis.
AB  - We previously found that some myeloma cell lines express the heparin-binding
      epidermal growth factor-like growth factor (HB-EGF) gene. As the proteoglycan
      syndecan-1 is an HB-EGF coreceptor as well as a hallmark of plasma cell
      differentiation and a marker of myeloma cells, we studied the role of HB-EGF on
      myeloma cell growth. The HB-EGF gene was expressed by bone marrow mononuclear
      cells in 8 of 8 patients with myeloma, particularly by monocytes and stromal
      cells, but not by purified primary myeloma cells. Six of 9 myeloma cell lines and
      9 of 9 purified primary myeloma cells expressed ErbB1 or ErbB4 genes coding for
      HB-EGF receptor. In the presence of a low interleukin-6 (IL-6) concentration, HB
      EGF stimulated the proliferation of the 6 ErbB1+ or ErbB4+ cell lines, through
      the phosphatidylinositol 3-kinase/AKT (PI-3K/AKT) pathway. A pan-ErbB inhibitor
      blocked the myeloma cell growth factor activity and the signaling induced by HB
      EGF. This inhibitor induced apoptosis of patients'myeloma cells cultured with
      their tumor environment. It also increased patients' myeloma cell apoptosis
      induced by an anti-IL-6 antibody or dexamethasone. The ErbB inhibitor had no
      effect on the interaction between multiple myeloma cells and stromal cells. It
      was not toxic for nonmyeloma cells present in patients' bone marrow cultures or
      for the growth of hematopoietic progenitors. Altogether, these data identify ErbB
      receptors as putative therapeutic targets in multiple myeloma.

PMID- 14576065
TI  - Isolation of multipotent mesenchymal stem cells from umbilical cord blood.
AB  - It is well accepted that umbilical cord blood has been a source for hematopoietic
      stem cells. However, controversy exists as to whether cord blood can serve as a
      source of mesenchymal stem cells, which can differentiate into cells of different
      connective tissue lineages such as bone, cartilage, and fat, and little success
      has been reported in the literature about the isolation of such cells from cord
      blood. Here we report a novel method to obtain single cell-derived, clonally
      expanded mesenchymal stem cells that are of multilineage differentiation
      potential by negative immunoselection and limiting dilution. The immunophenotype
      of these clonally expanded cells is consistent with that reported for bone marrow
      mesenchymal stem cells. Under appropriate induction conditions, these cells can
      differentiate into bone, cartilage, and fat. Surprisingly, these cells were also
      able to differentiate into neuroglial- and hepatocyte-like cells under
      appropriate induction conditions and, thus, these cells may be more than
      mesenchymal stem cells as evidenced by their ability to differentiate into cell
      types of all 3 germ layers. In conclusion, umbilical cord blood does contain
      mesenchymal stem cells and should not be regarded as medical waste. It can serve
      as an alternative source of mesenchymal stem cells to bone marrow.

PMID- 14576064
TI  - Geldanamycin and herbimycin A induce apoptotic killing of B chronic lymphocytic
      leukemia cells and augment the cells' sensitivity to cytotoxic drugs.
AB  - We studied the actions of geldanamycin (GA) and herbimycin A (HMA), inhibitors of
      the chaperone proteins Hsp90 and GRP94, on B chronic lymphocytic leukemia (CLL)
      cells in vitro. Both drugs induced apoptosis of the majority of CLL isolates
      studied. Whereas exposure to 4-hour pulses of 30 to 100 nM GA killed normal B
      lymphocytes and CLL cells with similar dose responses, T lymphocytes from healthy
      donors as well as those present in the CLL isolates were relatively resistant.
      GA, but not HMA, showed a modest cytoprotective effect toward CD34+ hematopoietic
      progenitors from normal bone marrow. The ability of bone marrow progenitors to
      form hematopoietic colonies was unaffected by pulse exposures to GA. Both GA and
      HMA synergized with chlorambucil and fludarabine in killing a subset of CLL
      isolates. GA- and HMA-induced apoptosis was preceded by the up-regulation of the
      stress-responsive chaperones Hsp70 and BiP. Both ansamycins also resulted in down
      regulation of Akt protein kinase, a modulator of cell survival. The relative
      resistance of T lymphocytes and of CD34+ bone marrow progenitors to GA coupled
      with its ability to induce apoptosis following brief exposures and to synergize
      with cytotoxic drugs warrant further investigation of ansamycins as potential
      therapeutic agents in CLL.

PMID- 14576066
TI  - Dual roles of the C-terminal Src kinase (Csk) during developmental
      vascularization.
AB  - Here we report that C-terminal Src kinase (Csk), a tyrosine kinase that
      negatively regulates the activity of Src and related kinases, is important for
      vascular development. In Csk(-/-) embryos, although vascular tubules were formed
      and organized into capillary-like networks during the initial genesis of blood
      vessels, the vessels failed to engage in normal sprout formation. In chimeric
      embryos containing both wild-type and Csk(-/-) cells, the presence of wild-type
      cells enabled Csk(-/-) endothelial cells to participate in branching
      morphogenesis. We suggest that wild-type cells may have supplied an angiogenic
      factor absent in Csk(-/-) cells. Despite the partial rescue of vascular
      development in chimeric embryos, the embryos failed to form vitelline vessels and
      died at E9.5. These results indicate that Csk is required both for angiogenic
      sprouting and vascular remodeling.

PMID- 14576067
TI  - Signaling by ephrinB1 and Eph kinases in platelets promotes Rap1 activation,
      platelet adhesion, and aggregation via effector pathways that do not require
      phosphorylation of ephrinB1.
AB  - We have previously shown that platelets express 2 receptor tyrosine kinases,
      EphA4 and EphB1, and the Eph kinase ligand, ephrinB1, and proposed that
      transcellular Eph/ephrin interactions made possible by the onset of platelet
      aggregation promote the further growth and stability of the hemostatic plug. The
      present study examines how this might occur. The results show that clustering of
      either ephrinB1 or EphA4 causes platelets to adhere to immobilized fibrinogen via
      alpha(IIb)beta(3). Adhesion occurs more slowly than with adenosine diphosphate
      (ADP) and requires phosphatidylinositol 3 (PI3)-kinase and protein kinase C
      activity but not ephrinB1 phosphorylation. By itself, Eph and ephrin signaling is
      insufficient to cause aggregation or the binding of soluble fibrinogen, but it
      can potentiate aggregation initiated by a Ca(++) ionophore or by agonists for
      thrombin and thromboxane receptors. It also enhances Rap1 activation without
      requiring ADP secretion, ephrinB1 phosphorylation, or the activation of PI3
      kinase and Src. From this we conclude that (1) Eph/ephrin signaling enhances the
      ability of platelet agonists to cause aggregation provided that those agonists
      can increase cytosolic Ca(++); (2) this is accomplished in part by activating
      Rap1; and (3) these effects require oligomerization of ephrinB1 but not
      phosphotyrosine-based interactions with the ephrinB1 cytoplasmic domain.

PMID- 14576068
TI  - Raf-1 is not required for megakaryocytopoiesis or TPO-induced ERK
      phosphorylation.
AB  - Thrombopoietin stimulates extracellular signal-related kinase 1/2 (ERK1/2)
      phosphorylation in megakaryocytes, and the classic mitogen-activated protein
      (MAP) kinase (Raf/mitogen-induced extracellular kinase [MEK]/ERK) pathway has
      been implicated directly and indirectly to play a critical role in
      megakaryocytopoiesis. However, the involvement of specific Raf family members in
      megakaryocytopoiesis is unknown. raf-1(-/-) mice were therefore used to directly
      determine the role of Raf-1 in megakaryocytopoiesis. Surprisingly, raf-1(-/-)
      mice have a modestly higher platelet count than their raf-1(+/+) littermates.
      Nonetheless, the absence of Raf-1 does not alter thrombopoietin-induced expansion
      of primary megakaryocyte-lineage cells, the development of apoptotic
      megakaryocytes in the presence or absence of thrombopoietin, or the development
      of megakaryocyte DNA ploidy distribution. Moreover, raf-1(-/-) megakaryocytes do
      not have a compensatory increase in A-Raf or B-Raf expression, and thrombopoietin
      induced ERK1/2 phosphorylation is similar in raf-1(-/-) and raf-1(+/+)
      megakaryocytes. These unexpected findings demonstrate that Raf-1 is dispensable
      for megakaryocytopoiesis, and for thrombopoietin-induced ERK1/2 activation in
      primary megakaryocyte-lineage cells.

PMID- 14576069
TI  - Relative increase in leukemia-specific DNA in peripheral blood plasma from
      patients with acute myeloid leukemia and myelodysplasia.
AB  - Using loss of heterozygosity (LOH) and X-chromosome inactivation, we compared
      peripheral blood (PB) plasma with bone marrow (BM) cells in detecting genomic
      abnormalities in patients with acute myeloid leukemia (AML) and myelodysplastic
      syndrome (MDS). We detected LOH in the PB plasma of all 45 patients who had
      cytogenetically documented chromosomal abnormalities (5q-, 7-, +8, 17-, or 20-).
      BM cells from the same patients showed LOH in 89% of patients with MDS and 70% of
      patients with AML. Posttherapy samples from 16 of these patients demonstrated
      complete concordance between LOH and cytogenetics in detecting residual disease
      in 15 samples. Of the 16 samples, 4 showed LOH in plasma with normal BM
      morphology. Using X-chromosome inactivation, clonality was detectable in 19 (73%)
      of 26 BM samples, whereas all PB plasma samples showed clonality. These data
      support the conclusion that PB plasma is enriched by tumor-specific DNA and can
      replace BM cells for studying genomic abnormalities.

PMID- 14576070
TI  - Antibody-induced intracellular signaling works in combination with radiation to
      eradicate lymphoma in radioimmunotherapy.
AB  - Radioimmunotherapy (RIT) has emerged as an effective treatment for lymphoma,
      however the underlying mechanisms are poorly understood. We therefore
      investigated the relative contributions of antibody and targeted radiation to the
      clearance of tumor in vivo, using 2 different syngeneic murine B-cell lymphoma
      models. Although RIT with (131)I-anti-major histocompatibility complex class II
      (MHCII) was effective in targeting radiation to tumor, no improvement in survival
      was seen by escalating the radiation dose alone and there were no long-term
      survivors. In contrast, using the combination of (131)I anti-MHCII in the
      presence of unlabeled anti-idiotype (anti-Id), 100% prolonged disease-free
      survival was seen in both B-cell lymphoma models at the higher radiation dose.
      Using in vivo tracking we show that treatment with radiation plus anti-Id
      monoclonal antibody (mAb) results in a substantially greater reduction of splenic
      tumor cells than with either treatment alone. Prolonged survival could also be
      achieved using (131)I anti-MHCII plus the signaling anti-CD19 mAb. Furthermore,
      the ability of these anti-B-cell mAbs to improve survival with targeted
      radiotherapy appeared to correlate with their ability to initiate intracellular
      signal transduction. Together these data illustrate that using 1 mAb to target
      radiation to tumor and a second to induce cell signaling is an effective new
      strategy in RIT.

PMID- 14576071
TI  - Long-term outcome of hepatitis C infection after bone marrow transplantation.
AB  - Chronic hepatitis C is often asymptomatic, at least during the first decade
      following hematopoietic stem cell transplantation. Progression to advanced liver
      disease or cirrhosis in patients surviving more than 10 years is currently
      thought to be rare. Among 1078 patients who underwent an allogeneic
      transplantation between January 1973 and January 1995, 96 patients infected by
      hepatitis C virus (HCV) during the transplantation period were studied.
      Cumulative incidence and analysis of risk factors for cirrhosis were analyzed,
      and the rate and risk of cirrhosis in transplant recipients were compared with
      those of 158 HCV-infected controls who did not receive transplants. At a median
      follow-up of 15.7 years, 15 patients developed biopsy-proven cirrhosis, leading
      to a cumulative incidence of cirrhosis of 11% and 24% at 15 and 20 years,
      respectively. By multivariate analysis, extrahepatic HCV manifestations and HCV
      genotype 3 were associated with risk of cirrhosis. The median time to cirrhosis
      in transplant recipients was 18 years as compared with 40 years in the control
      population. The risk of cirrhosis in transplant recipients relative to controls
      was significantly higher by multivariate analysis (P =.0008). Roughly a quarter
      of long-term HCV-infected survivors with transplants progressed to cirrhosis that
      is much more rapid than in patients without transplants. Systematic detection of
      HCV infection, liver biopsy, and therapeutic intervention are therefore warranted
      in long-term marrow transplant recipients.

PMID- 14576072
TI  - Gene expression in macrophage-rich inflammatory cell infiltrates in human
      atherosclerotic lesions as studied by laser microdissection and DNA array:
      overexpression of HMG-CoA reductase, colony stimulating factor receptors,
      CD11A/CD18 integrins, and interleukin receptors.
AB  - OBJECTIVE: Inflammatory cells play an important role in atherogenesis. However,
      more information is needed about their gene expression profiles in human lesions.
      METHODS AND RESULTS: We used laser microdissection (LMD) to isolate macrophage
      rich shoulder areas from human lesions. Gene expression profiles in isolated
      cells were analyzed by cDNA array and compared with expression patterns in normal
      intima and THP-1 macrophages. Upregulation of 72 genes was detected with LMD and
      included 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, interferon
      regulatory factor-5 (IRF-5), colony stimulating factor (CSF) receptors,
      CD11a/CD18 integrins, interleukin receptors, CD43, calmodulin, nitric oxide
      synthase (NOS), and extracellular superoxide dismutase (SOD). Several of these
      changes were also present in PMA-stimulated THP-1 macrophages in vitro. On the
      other hand, expression of several genes, such as VEGF, tissue factor pathway
      inhibitor 2, and apolipoproteins C-I and C-II, decreased. CONCLUSIONS:
      Overexpression of HMG-CoA reductase in macrophage-rich lesion areas may explain
      some beneficial effects of statins, which can also modulate increased expression
      of CD11a/CD18 and CD43 found in microdissected cells. We also found increased
      expression of CSF receptors, IRF-5, and interleukin receptors, which could become
      useful therapeutic targets for the treatment of atherosclerotic diseases.

PMID- 14576074
TI  - Soy protein with isoflavones, but not an isoflavone-rich supplement, improves
      arterial low-density lipoprotein metabolism and atherogenesis.
AB  - OBJECTIVE: We sought to determine if arterial LDL metabolism contributes to the
      decreased atherosclerosis seen with soy and if isolated isoflavones would have
      similar effects. METHODS AND RESULTS: Ovariectomized monkeys were fed an
      atherogenic diet for 20 weeks with a protein source of (1) casein/lactalbumin
      (CAS, n=20), (2) soy protein isolate (SOY, n=20), or (3) casein/lactalbumin with
      isolated soy isoflavones (ISO, n=17). Plasma lipoprotein concentrations were
      improved with SOY but not ISO. Arterial LDL metabolism was characterized with one
      subset (n=12/group) injected with dual-labeled tyramine-cellobiose (TC)-LDL (125I
      TC-131I-LDL) 24 hours before necropsy to determine LDL degradation and
      accumulation, while another subset (n=8/group) was injected with 125I-TC-LDL 1
      hour before necropsy to determine LDL permeability and delivery. CONCLUSIONS:
      Coronary artery LDL degradation was reduced by 50% (P=0.02) with SOY but not with
      ISO compared with CAS. Neither treatment altered arterial permeability. Reduced
      LDL degradation with SOY was due to decreased arterial LDL delivery (P=0.02).
      Carotid artery cholesterol ester was also decreased with SOY, but not with ISO.
      Plasma isoprostanes or plasma markers of inflammation did not differ among
      treatment groups. Thus, the decreased arterial LDL delivery and subsequent LDL
      degradation may explain, in part, the atheroprotective effects of soy.

PMID- 14576075
TI  - Flow-induced vascular remodeling in the mouse: a model for carotid intima-media
      thickening.
AB  - OBJECTIVE: Vascular remodeling of the carotid artery with intima-media thickness
      (IMT) is an important predictive factor for human cardiovascular disease. We
      characterized a mouse model of vascular remodeling. METHODS AND RESULTS: The left
      external and internal carotid branches were ligated so that left carotid blood
      flow was reduced to flow via the occipital artery. In response to partial
      ligation of the left carotid artery (LCA), blood flow significantly decreased (
      90%) in the LCA and increased (+70%) in the right carotid artery (RCA).
      Morphometry showed that both RCA and LCA underwent outward remodeling that was
      maximal at one week. Remodeling was greater in the RCA with predominantly
      increased lumen and very little increase in media or adventitia. In the LCA there
      was a dramatic increase in media with adventitia growth and intima formation.
      Correlation analysis indicated that the outward remodeling was more likely due to
      primary changes in the vessel wall rather than to changes in the lumen, such as
      shear stress. Mechanistic studies suggested roles for macrophage infiltration,
      upregulation of matrix metalloproteinase (MMP)-9, extracellular matrix
      reorganization, and vascular smooth muscle cell proliferation in LCA remodeling.
      CONCLUSIONS: The mouse model described here may be useful to define genetic
      determinants of IMT and identify new targets for therapy based on vascular
      remodeling.

PMID- 14576076
TI  - Cell structural changes in the needles of Norway spruce exposed to long-term
      ozone and drought.
AB  - Effects of ozone and/or drought on Norway spruce needles were studied using light
      microscopy and electron microscopy. Saplings were exposed to ozone in open-top
      chambers during 1992-1995 and also to drought in the late summers of 1993-1995.
      Samples from current and previous year needles were collected five times during
      1995. Ozone increased the numbers of peroxisomes and mitochondria, which suggests
      that defence mechanisms against oxidative stress were active. The results from
      peroxisomes suggest that the oxidative stress was more pronounced in the upper
      side of the needles, and those from mitochondria that defence was more active in
      the younger needle generation. Possibly due to the good nitrogen status and the
      active defence, no ozone-specific chloroplast alterations were seen. At the end
      of the season, older needles from ozone treatments had smaller central vacuoles
      compared with other needles. Cytoplasmic vacuoles around the nucleus were
      increased by ozone in the beginning of the experiment, and did not increase
      towards the end of the season as in the controls. These results from vacuoles may
      indicate that ozone affected the osmotic properties of the cells. Decreased
      number and underdevelopment of sclerenchyma cells and proliferation of tonoplast
      were related to nutrient imbalance, which was enhanced by drought. Larger
      vascular cylinders and more effective starch accumulation before and after the
      drought periods compensated for the reduced water status. Numbers of peroxisomes
      and mitochondria were increased in the drought-exposed needles before the onset
      of drought treatments of the study year, i.e. these changes were memory effects.
      Interactions between ozone and drought were few.

PMID- 14576077
TI  - The theory and application of plant competition models: an agronomic perspective.
AB  - Many studies of plant competition have been directed towards understanding how
      plants respond to density in monocultures and how the presence of weeds affects
      yield in crops. In this Botanical Briefing, the development and current
      understanding of plant competition is reviewed, with particular emphasis being
      placed on the theory of plant competition and the development and application of
      mathematical models to crop-weed competition and the dynamics of weeds in crops.
      By consolidating the results of past research in this manner, it is hoped to
      offer a context in which researchers can consider the potential directions for
      future research in competition studies and its application to integrated weed
      management.

PMID- 14576078
TI  - Neuropeptide Y enhances permeability across a rat aortic endothelial cell
      monolayer.
AB  - Previously, in vivo studies showed that neuropeptide Y (NPY) elevates vascular
      permeability in isolated lung perfusion preparations, possibly through binding to
      the NPY Y(3) receptor. The present study used monolayers in a double-chamber
      culture method under conditions of normoxia (5% CO(2)-20% O(2)-75% N(2)) or
      hypoxia (5% CO(2)-5% O(2)-90% N(2)) to test the hypothesis that NPY directly
      affects rat aortic endothelial cells (RAECs). RAECs were cultured on the base of
      the upper chamber, into which FITC-labeled albumin was introduced, and permeation
      into the lower chamber was measured. The RAEC monolayer was treated with 10(-8)-3
      x 10(-7) M NPY for 2 h in normoxia or hypoxia. In hypoxia, NPY concentration
      dependently increased the permeability of the RAEC monolayer, whereas in normoxia
      no significant change was observed. Peptide YY, NPY Y(1), and NPY Y(2) receptor
      agonists and NPY Y(1) receptor antagonist exerted no significant effects under
      hypoxic conditions. NPY-(18-36), an NPY Y(3) receptor antagonist, elicited an
      inhibitory action on the NPY-induced increase in monolayer permeability.
      Furthermore, neither N-monomethyl-l-arginine, a nitric oxide synthase inhibitor,
      the bradykinin B(2) receptor antagonist FK-3657, nor the vascular endothelial
      growth factor receptor-coupled tyrosine kinase inhibitor tyrphostin SU-1498,
      injected into the medium of the upper chamber, affected the NPY-induced
      permeability changes under hypoxic conditions. The results suggest that the NPY
      induced increase in permeability across the RAEC monolayer is closely related to
      low O(2) tension, possibly mediated by direct action on the NPY Y(3) receptor
      expressed on the endothelial cell membrane. Furthermore, this NPY-induced
      increase is not likely due to nitric oxide, bradykinin, or vascular endothelial
      growth factor.

PMID- 14576079
TI  - Are cardiovascular and sympathoadrenal effects of human "new pressor protein"
      preparations attributable to human coagulation beta-FXIIa?
AB  - "New pressor protein" (NPP) derived from normal human plasma is an extra renal
      enzyme that shares strong sequence homology with human coagulation beta-FXIIa.
      Under our bioassay conditions, human NPP (10-20 microl plasma equivalent/
      approximately 300 g rat iv) can raise the systolic blood pressure (SBP) by 40-50
      mmHg, the diastolic blood pressure (DBP) by 15-20 mmHg, and the heart rate (HR)
      by 70-90 beats/min. Plasma epinephrine (of adrenal medullary origin) and
      norepinephrine rise by about 50- and 10-fold, respectively. Because beta-FXIIa is
      not normally associated with pressor properties, we endeavored to substantiate
      that the hypertensive effects of impure NPP preparations used in our experiments
      are attributable to their content of beta-FXIIa. We carried out comparisons with
      highly purified (>90%) commercial human beta-FXIIa and found that by gel
      filtration (Sephadex G-100 and G-75), NPP bioactivity appeared in the
      approximately 30-kDa elution zone, consistent with the molecular mass of beta
      FXIIa. Retention time using fast-protein liquid chromatography anion exchange
      chromatography was identical. Molecular mass and comigration were confirmed by
      SDS-PAGE gel electrophoresis, and the recovered approximately 30-kDa protein
      bands yielded beta-FXIIa fragments identified by mass spectrometry. Matched doses
      of the NPP preparations produced dose-response curves very similar to those
      elicited by beta-FXIIa with respect to increments of SBP, DBP, and HR, whereas
      plasma catecholamine increments were generally comparable. We propose that beta
      FXIIa is substantially, if not exclusively, responsible for the observed effects
      of our NPP preparations and that this points to a novel axis connecting the FXII
      coagulation cascade and the sympathoadrenal gland to other cardiovascular
      regulatory mechanisms.

PMID- 14576080
TI  - Superoxide, H2O2, and iron are required for TNF-alpha-induced MCP-1 gene
      expression in endothelial cells: role of Rac1 and NADPH oxidase.
AB  - Reactive oxygen species (ROS) play an important but not yet fully defined role in
      the expression of inflammatory genes such as monocyte chemoattractant protein
      (MCP)-1. We used complementary molecular and biochemical approaches to explore
      the roles of specific ROS and their molecular linkage to inflammatory signaling
      in endothelial cells. Adenovirus-mediated expression of superoxide dismutase and
      catalase inhibited TNF-alpha-induced MCP-1 gene expression, suggesting important
      roles of superoxide (O(2)(-).) and H(2)O(2) in MCP-1 gene activation. In
      addition, the iron chelator 1,2-dimethyl-3-hydroxypyridin-4-one and the hydroxyl
      radical scavengers dimethylthiourea and dimethyl sulfoxide inhibited TNF-alpha
      induced MCP-1 expression, suggesting important roles of iron and hydroxyl
      radicals in inflammatory signal activation. In contrast, scavenging of
      peroxynitrite with 5,10,15,20-tetrakis-(4-sulfonatophenyl)prophyrinato iron (III)
      chloride had no effect on TNF-alpha-induced MCP-1 expression. Inhibition of NADPH
      oxidase, the major oxidase responsible for O(2)(-). generation, with diphenylene
      iodonium suppressed TNF-alpha-induced MCP-1 mRNA accumulation. Rac1 is an
      upstream signaling molecule for the activation of NADPH oxidase and O(2)(-).
      generation. Expression of dominant negative N17Rac1 by adenovirus suppressed TNF
      alpha-induced MCP-1 mRNA levels and MCP-1 protein secretion. Expression of
      N17Rac1 inhibited TNF-alpha-induced MCP-1 and NF-kappaB transcriptional activity.
      These data suggest that ROS such as superoxide and H(2)O(2) derived from Rac1
      activated NADPH oxidase mediate TNF-alpha-induced MCP-1 expression in endothelial
      cells.

PMID- 14576081
TI  - Decreased skeletal muscle pump activity in patients with postural tachycardia
      syndrome and low peripheral blood flow.
AB  - Standing translocates thoracic blood volume into the dependent body. The skeletal
      muscle pump participates in preventing orthostatic intolerance by enhancing
      venous return. We investigated the hypothesis that skeletal muscle pump function
      is impaired in postural tachycardia (POTS) associated with low calf blood flow
      (low-flow POTS) and depends in general on muscle blood flow. We compared 12
      subjects that have low-flow POTS with 10 controls and 7 patients that have POTS
      and normal calf blood flow using strain-gauge plethysmography to measure
      peripheral blood flow, venous capacitance, and calf muscle pump function. Blood
      volume was estimated by dye dilution. We found that calf circumference was
      reduced in low-flow POTS (32 +/- 1 vs. 39 +/- 3 and 43 +/- 3 cm) and, compared
      with controls and POTS patients with normal blood flow, is related to the reduced
      fraction of calf venous capacity emptied during voluntary muscle contraction
      (ejection fraction, 0.52 +/- 0.07 vs. 0.76 +/- 0.07 and 0.80 +/- 0.06). We found
      that blood flow was linearly correlated (r(p) = 0.69) with calf circumference
      (used as a surrogate for muscle mass). Blood volume measurements were 2.2 +/- 0.3
      in low-flow POTS vs. 2.6 +/- 0.5 in controls (P = 0.17) and 2.4 +/- 0.7 in normal
      flow POTS patients. Decreased calf blood flow may reduce calf size in POTS and
      thereby impair the upright ejective ability of the skeletal muscle pump and
      further contribute to overall reduced blood flow and orthostatic intolerance in
      these patients.

PMID- 14576082
TI  - Acute and specific collagen type I degradation increases diastolic and developed
      tension in perfused rat papillary muscle.
AB  - Collagen degradation is suggested to be responsible for long-term contractile
      dysfunction in different cardiomyopathies, but the effects of acute and specific
      collagen type I removal (main type in the heart muscle) on tension have not been
      studied. We determined the diastolic and developed tension length relations in
      isometric contracting perfused rat papillary muscles (perfusion pressure 60
      cmH(2)O) before and after acute and specific removal of small collagen struts
      with the use of purified collagenase type I. At 95% of the maximal length
      (95%L(max)), diastolic tension increased 20.4 +/- 8.1% (P < 0.05, n = 6) and
      developed tension increased 15.0 +/- 6.7% after collagenase treatment compared
      with time controls. Treatment increased the diastolic muscle diameter by 7.1 +/-
      3.4% at 95%L(max), whereas the change in diameter due to contraction was not
      changed. Diastolic coronary flow and normalized coronary arterial flow impediment
      did not change after collagenase treatment. Electron microscopy revealed that the
      number of small collagen struts, interconnecting myocytes, and capillaries was
      reduced to approximately 32% after treatment. We conclude that removal of the
      small collagen struts by acute and specific collagen type I degradation increases
      diastolic and developed tension in perfused papillary muscle. We suggest that
      diastolic tension is increased due to edema, whereas developed tension is
      increased because the removal of the struts poses a lower lateral load on the
      cardiac myocytes, allowing more myocyte thickening.

PMID- 14576083
TI  - 5-HT induces duodenal mucosal bicarbonate secretion via cAMP- and Ca2+-dependent
      signaling pathways and 5-HT4 receptors in mice.
AB  - In previous studies, we have found that 5-hydroxytryptamine (5-HT) is a potent
      stimulant of duodenal mucosal bicarbonate secretion (DMBS) in mice. The aim of
      the present study was to determine the intracellular signaling pathways and 5-HT
      receptor subtypes involved in 5-HT-induced DMBS. Bicarbonate secretion by murine
      duodenal mucosa was examined in vitro in Ussing chambers. 5-HT receptor
      involvement in DMBS was inferred from pharmacological studies by using selective
      5-HT receptor antagonists and agonists. The expression of 5-HT(4) receptor mRNA
      in duodenal mucosa and epithelial cells was analyzed by RT-PCR. cAMP-dependent
      signaling pathway inhibitors MDL-12330A, Rp-cAMP, and H-89 and Ca(2+)-dependent
      signaling pathway inhibitors verapamil and W-13 markedly reduced 5-HT-stimulated
      duodenal bicarbonate secretion and short-circuit current (I(sc)), whereas cGMP
      dependent signaling pathway inhibitors NS-2028 and KT-5823 failed to alter these
      responses. Both SB-204070 and high-dose ICS-205930 (selective 5-HT(4) receptor
      antagonists) markedly inhibited 5-HT-stimulated bicarbonate secretion and I(sc),
      whereas methiothepine (5-HT(1) receptor antagonist), ketanserin (5-HT(2) receptor
      antagonist), and a low concentration of ICS-205930 (5-HT(3) receptor antagonist)
      had no effect. RS-67506 (partial 5-HT(4) receptor agonist) concentration
      dependently increased bicarbonate secretion and I(sc), whereas 5
      carboxamidotryptamine (5-HT(1) receptor agonist), alpha-methyl-5-HT (5-HT(2)
      receptor agonist), and phenylbiguanide (5-HT(3) receptor agonist) did not
      significantly increase bicarbonate secretion or I(sc). RT-PCR analysis confirmed
      the expression of 5-HT(4) receptor mRNA in murine duodenal mucosa and epithelial
      cells. These results demonstrate that 5-HT regulates DMBS via both cAMP- and
      Ca(2+)-dependent signaling pathways and 5-HT(4) receptors located in the duodenal
      mucosa and/or epithelial cells.

PMID- 14576084
TI  - Tension development during contractile stimulation of smooth muscle requires
      recruitment of paxillin and vinculin to the membrane.
AB  - Cytoskeletal reorganization of the smooth muscle cell in response to contractile
      stimulation may be an important fundamental process in regulation of tension
      development. We used confocal microscopy to analyze the effects of cholinergic
      stimulation on localization of the cytoskeletal proteins vinculin, paxillin,
      talin and focal adhesion kinase (FAK) in freshly dissociated tracheal smooth
      muscle cells. All four proteins were localized at the membrane and throughout the
      cytoplasm of unstimulated cells, but their concentration at the membrane was
      greater in acetylcholine (ACh)-stimulated cells. Antisense oligonucleotides were
      introduced into tracheal smooth muscle tissues to deplete paxillin protein, which
      also inhibited contraction in response to ACh. In cells dissociated from paxillin
      depleted muscle tissues, redistribution of vinculin to the membrane in response
      to ACh was prevented, but redistribution of FAK and talin was not inhibited.
      Muscle tissues were transfected with plasmids encoding a paxillin mutant
      containing a deletion of the LIM3 domain (paxillin LIM3 dl 444-494), the primary
      determinant for targeting paxillin to focal adhesions. Expression of paxillin
      LIM3 dl in muscle tissues also inhibited contractile force and prevented cellular
      redistribution of paxillin and vinculin to the membrane in response to ACh, but
      paxillin LIM3 dl did not inhibit increases in intracellular Ca2+ or myosin light
      chain phosphorylation. Our results demonstrate that recruitment of paxillin and
      vinculin to smooth muscle membrane is necessary for tension development and that
      recruitment of vinculin to the membrane is regulated by paxillin. Vinculin and
      paxillin may participate in regulating the formation of linkages between the
      cytoskeleton and integrin proteins that mediate tension transmission between the
      contractile apparatus and the extracellular matrix during smooth muscle
      contraction.

PMID- 14576085
TI  - Rb regulates C/EBPbeta-DNA-binding activity during 3T3-L1 adipogenesis.
AB  - Two pathways are initiated upon 3T3-L1 preadipocyte differentiation: the reentry
      of cells into the cell cycle and the initiation of a cascade of transcriptional
      events that "prime" the cell for differentiation. The "priming" event involves
      the synthesis of members of the CCAAT/enhancer binding protein (C/EBP) family of
      transcription factors. However, the relationship between these two pathways is
      unknown. Here we report that in the 3T3-L1 preadipocytes induced to
      differentiate, cell cycle progression and the initiation of differentiation are
      linked by a cell cycle-dependent Rb-C/EBPbeta interaction. Cell cycle arrest in
      G1 by l-mimosine inhibited differentiation-induced C/EBPbeta-DNA-binding activity
      and Rb phosphorylation. However, cell cycle arrest after the G1/S transition by
      aphidicolin or nocodazole did not prevent C/EBPbeta-DNA-binding activity or Rb
      phosphorylation. Furthermore, hypophosphorylated Rb and C/EBPbeta
      coimmunoprecipitated, whereas phosphorylated Rb and C/EBPbeta did not.
      Electrophoretic mobility shift assays demonstrated that recombinant
      hypophosphorylated Rb decreased C/EBPbeta-DNA-binding activity and that Rb
      overexpression inhibited C/EBPbeta-induced transcriptional activation of a
      C/EBPalpha-promoter-luciferase reporter gene. We conclude that C/EBPbeta-DNA
      binding activity is regulated by its interaction with hypophosphorylated Rb,
      thereby linking the progression of the cell cycle to the initiation of
      differentiation during 3T3-L1 adipogenesis.

PMID- 14576086
TI  - Copper-inducible transcription: regulation by metal- and oxidative stress
      responsive pathways.
AB  - Although copper is an essential metal, it is capable of catalyzing the formation
      of reactive oxygen species that can cause intracellular oxidative damage. We
      investigated the hypothesis that metal- and oxidative stress-responsive signal
      transduction pathways mediate the cellular and molecular responses associated
      with copper exposure. Transient transfection assays using COS-7 cells and mouse
      metallothionein-I (MT-I) or rat NAD(P)H:oxidoreductase 1-based reporter genes
      demonstrate that copper activates transcription via metal and antioxidant
      response elements. Concomitant with copper exposures is a decrease in the level
      of total glutathione and an increase in oxidized glutathione. Depletion of
      glutathione, before copper exposure, increases metal- and oxidative stress
      inducible transcription and cytotoxicity. Pretreatment with the reactive oxygen
      scavengers aspirin or vitamin E provides partial protection against copper
      toxicity and reduces inducible transcription. Experiments using signal
      transduction inhibitors and a metal transcription factor (MTF)-1 null cell line
      demonstrate that copper-inducible MT-I transcription is regulated by protein
      kinase C and mitogen-activated protein kinase signaling pathways and requires MTF
      1. The results of these studies indicate that copper activates transcription
      through both metal- and oxidative stress-responsive signal transduction pathways.

PMID- 14576087
TI  - Sevenfold-reduced osmotic water permeability in primary astrocyte cultures from
      AQP-4-deficient mice, measured by a fluorescence quenching method.
AB  - A calcein fluorescence quenching method was applied to measure osmotic water
      permeability in highly differentiated primary cultures of brain astrocytes from
      wild-type and aquaporin-4 (AQP-4)-deficient mice. Cells grown on coverglasses
      were loaded with calcein for measurement of volume changes after osmotic
      challenge. Hypotonic shock producing twofold cell swelling resulted in a
      reversible approximately 12% increase in calcein fluorescence, which was
      independent of cytosolic calcein concentration at levels well below where calcein
      self-quenching occurs. Calcein fluorescence was quenched in <200 ms in response
      to addition of cytosol in vitro, indicating that the fluorescence signal arises
      from changes in cytosol concentration. In astrocytes from wild-type CD1 mice,
      calcein fluorescence increased reversibly in response to hypotonic challenge with
      a half-time of 0.92 +/- 0.05 s at 23 degrees C, corresponding to an osmotic water
      permeability (Pf) of approximately 0.05 cm/s. Pf was reduced 7.1-fold in
      astrocytes from AQP-4-deficient mice. Temperature dependence studies indicated an
      increased Arrhenius activation energy for water transport in AQP-4-deficient
      astrocytes (11.3 +/- 0.5 vs. 5.5 +/- 0.4 kcal/mol). Our studies establish a
      calcein quenching method for measurement of cell membrane water permeability and
      indicate that AQP-4 provides the principal route for water transport in
      astrocytes.

PMID- 14576088
TI  - Differential aggregation properties of secretory proteins that are stored in
      exocrine secretory granules of the pancreas and parotid glands.
AB  - Low-pH- and calcium-induced aggregation of regulated secretory proteins has been
      proposed to play a role in their retention and storage in secretory granules.
      However, this has not been tested for secretory proteins that are stored in the
      exocrine parotid secretory granules. Parotid granule matrix proteins were
      analyzed for aggregation in the presence or absence of calcium and in the pH
      range of 5.5 to 7.5. Amylase did not aggregate under these conditions, although
      <10% of parotid secretory protein (PSP) aggregated below pH 6.0. To test
      aggregation directly in isolated granules, rat parotid secretory granules were
      permeabilized with 0.1% saponin in the presence or absence of calcium and in the
      pH range of 5.0 to 8.4. In contrast to the low-pH-dependent retention of amylase
      in exocrine pancreatic granules, amylase was quantitatively released and most PSP
      was released from parotid granules under all conditions. Both proteins were
      completely released upon granule membrane solubilization. Thus neither amylase
      nor PSP show low-pH- or calcium-induced aggregation under physiological
      conditions in the exocrine parotid secretory granules.

PMID- 14576089
TI  - Amiloride-sensitive epithelial Na+ channel currents in surface cells of rat
      rectal colon.
AB  - Surface cells of the mammalian distal colon are shown to molecularly express the
      amiloride-sensitive epithelial Na+ channel composed of three homologous subunits
      (alpha-, beta-, and gamma-ENaC). However, because basic electrophysiological
      properties of amiloride-sensitive Na+ channels expressed in these cells are
      largely unknown at the cellular level, functional evidence for the involvement of
      the subunits in the native channels is incomplete. Using electrophysiological
      techniques, we have now characterized functional properties of native ENaC in
      surface cells of rectal colon (RC) of rats fed a normal Na+ diet. Ussing chamber
      experiments showed that apical amiloride inhibited a basal short-circuit current
      in mucosal preparation of RC with an apparent half-inhibition constant (Ki) value
      of 0.20 microM. RT-PCR analysis confirmed the presence of transcripts of alpha-,
      beta-, and gamma-rENaC in rectal mucosa. Whole cell patch-clamp experiments in
      surface cells of intact crypts acutely isolated from rectal mucosa identified an
      inward cationic current, which was inhibited by amiloride with a Ki value of 0.12
      microM at a membrane potential of -64 mV, the inhibition being weakly voltage
      dependent. Conductance ratios of the currents were Li+ (1.8) > Na+ (1) >> K+ (
      approximately 0), respectively. Amiloride-sensitive current amplitude was almost
      the same at 15 or 150 mM extracellular Na+, suggesting a high Na+ affinity for
      current activation. These results are consistent with the hypothesis that a
      heterooligomer composed of alpha-, beta-, and gamma-ENaC may be the molecular
      basis of the native channels, which are responsible for amiloride-sensitive
      electrogenic Na+ absorption in rat rectal colon.

PMID- 14576090
TI  - System-specific O2 sensitivity of the tandem pore domain K+ channel TASK-1.
AB  - Hypoxic inhibition of TASK-1, a tandem pore domain background K+ channel,
      provides a critical link between reduced O2 levels and physiological responses in
      various cell types. Here, we examined the expression and O2 sensitivity of TASK-1
      in immortalized adrenomedullary chromaffin (MAH) cells. In physiological
      (asymmetrical) K+ solutions, 3 microM anandamide or 300 microM Zn2+ inhibited a
      strongly pH-sensitive current. Under symmetrical K+ conditions, the anandamide-
      and Zn2+-sensitive K+ currents were voltage independent. These data demonstrate
      the functional expression of TASK-1, and cellular expression of this channel was
      confirmed by RT-PCR and Western blotting. At concentrations that selectively
      inhibit TASK-1, anandamide and Zn2+ were without effect on the magnitude of the
      O2-sensitive current or the hypoxic depolarization. Thus TASK-1 does not
      contribute to O2 sensing in MAH cells, demonstrating the failure of a known O2
      sensitive K+ channel to respond to hypoxia in an O2-sensing cell. These data
      demonstrate that, ultimately, the sensitivity of a particular K+ channel to
      hypoxia is determined by the cell, and we propose that this is achieved by
      coupling distinct hypoxia signaling systems to individual channels. Importantly,
      these data also reiterate the indirect O2 sensitivity of TASK-1, which appears to
      require the presence of an intracellular mediator.

PMID- 14576091
TI  - Molecular impact of the M184V mutation in human immunodeficiency virus type 1
      reverse transcriptase.

PMID- 14576093
TI  - In vitro-in vivo model for evaluating the antiviral activity of amprenavir in
      combination with ritonavir administered at 600 and 100 milligrams, respectively,
      every 12 hours.
AB  - The study objective was to evaluate the pharmacodynamics of amprenavir in an in
      vitro system, develop an exposure target for maximal viral suppression, and
      determine the likelihood of target attainment based on the pharmacokinetics of
      amprenavir and ritonavir in human immunodeficiency virus (HIV)-infected patients.
      Population pharmacokinetic data were obtained from 13 HIV-infected patients
      receiving amprenavir and ritonavir in doses of 600 and 100 mg, respectively,
      every 12 h. A 2,500-subject Monte Carlo simulation was performed. Target
      attainment was also estimated for a target derived from clinical data. Maximal
      viral suppression (in vitro) was achieved when amprenavir free-drug
      concentrations remained greater than four times the 50% effective concentration
      (EC(50)) for 80% of the dosing interval. At an amprenavir EC(50) of 0.03 microM,
      the likelihood of target attainment is 97.4%. For reduced-susceptibility isolates
      for which the EC(50)s are 0.05 and 0.08 microM, target attainment is 91.0 and
      75.8%, respectively. For the clinical target of a trough concentration/EC(50)
      ratio of 5, the target attainment rates were similar. Treatment with amprenavir
      and ritonavir at doses of 600 and 100 mg, respectively, twice a day provides
      excellent suppression of wild-type isolates and reduced-susceptibility isolates
      up to an EC(50) of 0.05 micro M. Even at 0.12 microM, target attainment
      likelihood exceeds 50%, making this an option for patients with extensive
      exposure to protease inhibitors when this treatment is used with additional
      active antiretroviral agents.

PMID- 14576092
TI  - Mitochondrial and metabolic effects of nucleoside reverse transcriptase
      inhibitors (NRTIs) in mice receiving one of five single- and three dual-NRTI
      treatments.
AB  - Although treatments with nucleoside reverse transcriptase inhibitors (NRTIs) can
      modify fat metabolism and fat distribution in humans, the mechanisms of these
      modifications and the roles of diverse NRTIs are unknown. We studied the
      mitochondrial and metabolic effects of stavudine (d4T), zidovudine (AZT),
      didanosine (ddI), lamivudine (3TC), zalcitabine (ddC), and three combinations
      (AZT-3TC, d4T-3TC, and d4T-ddI) in mice treated for 2 weeks with daily doses
      equivalent to the human dose per body area. Concentrations of AZT and d4T in
      plasma were lower when these drugs were administered with 3TC or ddI. Whatever
      the treatment, mitochondrial DNA was not significantly decreased in muscle,
      heart, brain, or white adipose tissue but was moderately decreased in liver
      tissue after the administration of AZT, 3TC, or d4T alone. Blood lactate was
      unchanged, even when NRTIs were administered at supratherapeutic doses. In
      contrast, the level of plasma ketone bodies increased with the administration of
      AZT or high doses of d4T but not with ddC, 3TC, or ddI, suggesting that the
      thymine moiety could be involved. Indeed, the levels of plasma ketone bodies
      increased in mice treated with beta-aminoisobutyric acid, a thymine catabolite.
      Treatment with AZT, d4T, or beta-aminoisobutyric acid increased hepatic carnitine
      palmitoyltransferase I (CPT-I) mRNA expression and the mitochondrial generation
      of ketone bodies from palmitate. In conclusion, therapeutic doses of NRTIs have
      no or moderate effects on mitochondrial DNA and no effects on plasma lactate in
      mice. However, AZT and high doses of d4T increase the levels of hepatic CPT-I,
      mitochondrial fatty acid beta-oxidation, and ketone bodies, and these catabolic
      effects are reproduced by beta-aminoisobutyric acid, a thymine metabolite.

PMID- 14576094
TI  - Anti-clumping factor A immunoglobulin reduces the duration of methicillin
      resistant Staphylococcus aureus bacteremia in an experimental model of infective
      endocarditis.
AB  - SA-IGIV is a human polyclonal immunoglobulin containing elevated levels of
      antibodies specific for the fibrinogen-binding MSCRAMM protein clumping factor A
      (ClfA). In vitro, SA-IGIV specifically recognized ClfA that was expressed on the
      surface of Staphylococcus aureus and inhibited bacterial adherence to immobilized
      human fibrinogen by >95%. Moreover, SA-IGIV efficiently opsonized ClfA-coated
      fluorescent beads and facilitated phagocytosis by human polymorphonuclear
      leukocytes. To determine its potential therapeutic efficacy, SA-IGIV was
      evaluated in combination with vancomycin in a rabbit model of catheter-induced
      aortic valve infective endocarditis (IE) caused by methicillin-resistant S.
      aureus (MRSA). The combination therapy was more effective than vancomycin alone
      in sterilizing all valvular vegetations when used therapeutically during early
      (12-h) IE. The combination therapy resulted in clearance of bacteremia that was
      significantly faster than that of vancomycin alone in animals with well
      established (24-h) IE. Therefore, in both early and well-established MRSA IE, the
      addition of SA-IGIV to a standard antibiotic regimen (vancomycin) increased
      bacterial clearance from the bloodstream and/or vegetations.

PMID- 14576096
TI  - Heterogeneity of macrolide-lincosamide-streptogramin B resistance phenotypes in
      enterococci.
AB  - We determined the macrolide resistance phenotypes of 241 clinical isolates of
      erythromycin-resistant enterococci (MICs, > or = 1 microg/ml), including 147
      Enterococcus faecalis strains and 94 Enterococcus faecium strains, collected from
      a hospital in Seoul, Korea, between 1999 and 2000. By the erythromycin (40 micro
      g)-josamycin (100 microg) double-disk test, 93 strains were assigned to the
      constitutive macrolide, lincosamide, and streptogramin B (MLS(B)) resistance
      (cMLS(B)) phenotype, and the remaining 148 strains were assigned to the inducible
      MLS(B) resistance (iMLS(B)) phenotype. Of the strains with the iMLS(B) phenotype,
      36 exhibited a reversibly inducible MLS(B) (riMLS(B)) phenotype, i.e., blunting
      of the erythromycin zone of inhibition, which indicates that the 16-membered-ring
      macrolide josamycin is a more effective inducer than the 14-membered-ring
      macrolide erythromycin. Sequence analysis of the regulatory regions of the erm(B)
      genes from all of the strains exhibiting the riMLS(B) phenotype revealed not only
      erm(Bv) [where v represents variant; previously erm(AMR)] (n = 13), as reported
      previously, but also three kinds of erm(B) variants, which were designated
      erm(Bv1) (n = 17), erm(Bv2) (n = 3), and erm(Bv3) (n = 3), respectively. In lacZ
      reporter gene assays of these variants, the 16-membered-ring macrolide tylosin
      had stronger inducibility than erythromycin at > or = 0.1 microg/ml. These
      findings highlight the versatility of erm(B) in induction specificity.

PMID- 14576095
TI  - Lysostaphin disrupts Staphylococcus aureus and Staphylococcus epidermidis
      biofilms on artificial surfaces.
AB  - Staphylococci often form biofilms, sessile communities of microcolonies encased
      in an extracellular matrix that adhere to biomedical implants or damaged tissue.
      Infections associated with biofilms are difficult to treat, and it is estimated
      that sessile bacteria in biofilms are 1,000 to 1,500 times more resistant to
      antibiotics than their planktonic counterparts. This antibiotic resistance of
      biofilms often leads to the failure of conventional antibiotic therapy and
      necessitates the removal of infected devices. Lysostaphin is a glycylglycine
      endopeptidase which specifically cleaves the pentaglycine cross bridges found in
      the staphylococcal peptidoglycan. Lysostaphin kills Staphylococcus aureus within
      minutes (MIC at which 90% of the strains are inhibited [MIC(90)], 0.001 to 0.064
      microg/ml) and is also effective against Staphylococcus epidermidis at higher
      concentrations (MIC(90), 12.5 to 64 microg/ml). The activity of lysostaphin
      against staphylococci present in biofilms compared to those of other antibiotics
      was, however, never explored. Surprisingly, lysostaphin not only killed S. aureus
      in biofilms but also disrupted the extracellular matrix of S. aureus biofilms in
      vitro on plastic and glass surfaces at concentrations as low as 1 microg/ml.
      Scanning electron microscopy confirmed that lysostaphin eradicated both the
      sessile cells and the extracellular matrix of the biofilm. This disruption of S.
      aureus biofilms was specific for lysostaphin-sensitive S. aureus, as biofilms of
      lysostaphin-resistant S. aureus were not affected. High concentrations of
      oxacillin (400 microg/ml), vancomycin (800 microg/ml), and clindamycin (800
      microg/ml) had no effect on the established S. aureus biofilms in this system,
      even after 24 h. Higher concentrations of lysostaphin also disrupted S.
      epidermidis biofilms.

PMID- 14576098
TI  - Interlaboratory comparison of agar dilution and Etest methods for determining the
      MICs of antibiotics used in management of Neisseria meningitidis infections.
AB  - Previous studies have shown that there is considerable variation in the methods
      and media used to determine the susceptibility of Neisseria meningitidis to
      antimicrobial agents in different countries. In this study, national and regional
      reference laboratories used a standardized methodology to determine the MICs of
      antibiotics used in the management of meningococcal infection. Fourteen
      laboratories participated in the study, determining the susceptibility to
      penicillin G, rifampin, cefotaxime, ceftriaxone, ciprofloxacin, and ofloxacin of
      a collection of 17 meningococci, of which 11 strains were previously defined as
      having intermediate resistance to penicillin (Pen(I)) by sequencing and
      restriction fragment length polymorphism analysis of the penA gene. The MIC was
      determined by agar dilution and Etest with Mueller-Hinton agar (MH), MH
      supplemented with sheep blood (MH+B), and MH supplemented with heated
      (chocolated) blood. Several laboratories encountered problems obtaining confluent
      growth with unsupplemented MH. MH+B was considered to give the most congruent and
      reproducible results among the study laboratories. The modal MIC for MH+B for
      each antibiotic and method was calculated to define the MIC consensus, allowing
      assessment of each individual laboratory's data in relation to the others. The
      agreement in each antibiotic/method/medium combination was defined as the
      percentage of laboratories with a result within one dilution of the modal result.
      For the whole study, an agreement of 90.6% was observed between agar dilution and
      Etest methods. The agreement in each laboratory/antibiotic/method combination
      ranged from 98.2% to 69.7%, with six laboratories demonstrating agreement higher
      than 90% and 11 more than 80%. The ability of the laboratories to detect the
      Pen(I) isolates ranged from 18.2% to 100%. The apparent difficulty in
      interpreting susceptibility to rifampin, particularly with the Etest method, is
      very interesting.

PMID- 14576099
TI  - Synthesis, degradation, and antimicrobial properties of targeted macromolecular
      prodrugs of norfloxacin.
AB  - Long-term antibiotic treatment is required to cure tuberculosis. Targeted
      antibiotics should improve the efficacy of treatment by concentrating the drugs
      close to the bacteria. The aim of the present study was to synthesize targeted
      conjugates. For this purpose, we used mannose as a homing device to direct
      norfloxacin into macrophages. Dextran was used as the polymer bearing both
      mannose and norfloxacin. Using different peptide spacer arms to link norfloxacin
      to dextran, we demonstrated that norfloxacin acts as an antibiotic only when it
      is released in its native form. Also, targeting by using mannose as a homing
      device is required to achieve antimycobacterial activity in vivo. Thus,
      norfloxacin, which is inactive against mycobacteria in its native form in vivo,
      can be transformed into an active drug by targeting.

PMID- 14576097
TI  - CesRK, a two-component signal transduction system in Listeria monocytogenes,
      responds to the presence of cell wall-acting antibiotics and affects beta-lactam
      resistance.
AB  - Listeria monocytogenes is a food-borne pathogen that can cause a variety of
      illnesses ranging from gastroenteritis to life-threatening septicemia. The beta
      lactam antibiotic ampicillin remains the drug of choice for the treatment of
      listeriosis. We have previously identified a response regulator of a putative two
      component signal transduction system that plays a role in the virulence and
      ethanol tolerance of L. monocytogenes. Here we present evidence that the response
      regulator, CesR, and a histidine protein kinase, CesK, which is encoded by the
      gene downstream from cesR, are involved in the ability of L. monocytogenes to
      tolerate ethanol and cell wall-acting antibiotics of the beta-lactam family.
      Furthermore, CesRK controls the expression of a putative extracellular peptide
      encoded by the orf2420 gene, located immediately downstream from cesRK.
      Inactivation of orf2420 revealed that it contributes to ethanol tolerance and
      pathogenesis in mice. Interestingly, we found that transcription of orf2420 was
      strongly induced by subinhibitory concentrations of various cell wall-acting
      antibiotics, ethanol, and lysozyme. The induction of orf2420 expression was
      abolished in the absence of CesRK. Our data suggest that CesRK is involved in
      regulating aspects of the cell envelope architecture and that changes in cell
      wall integrity provide a potent stimulus for CesRK-mediated regulation. These
      results further our understanding of how L. monocytogenes senses and responds to
      antibiotics that are used therapeutically in the treatment of infectious
      diseases.

PMID- 14576100
TI  - Cefepime versus imipenem-cilastatin for treatment of nosocomial pneumonia in
      intensive care unit patients: a multicenter, evaluator-blind, prospective,
      randomized study.
AB  - In a randomized, evaluator-blind, multicenter trial, we compared cefepime (2 g
      three times a day) with imipenem-cilastatin (500 mg four times a day) for the
      treatment of nosocomial pneumonia in 281 intensive care unit patients from 13
      centers in six European countries. Of 209 patients eligible for per-protocol
      analysis of efficacy, favorable clinical responses were achieved in 76 of 108
      (70%) patients treated with cefepime and 75 of 101 (74%) patients treated with
      imipenem-cilastatin. The 95% confidence interval (CI) for the difference between
      these response rates (-16 to 8%) failed to exclude the predefined lower limit for
      noninferiority of -15%. In addition, therapy of pneumonia caused by an organism
      producing an extended-spectrum beta-lactamase (ESBL) failed in 4 of 13 patients
      in the cefepime group but in none of 10 patients in the imipenem group. However,
      the clinical efficacies of both treatments appeared to be similar in a secondary
      intent-to-treat analysis (95% CI for difference, -9 to 14%) and a multivariate
      analysis (95% CI for odds ratio, 0.47 to 1.75). Furthermore, the all-cause 30-day
      mortality rates were 28 of 108 (26%) patients in the cefepime group and 19 of 101
      (19%) patients in the imipenem group (P = 0.25). Rates of documented or presumed
      microbiological eradication of the causative organism were similar with cefepime
      (61%) and imipenem-cilastatin (54%) (95% CI, -23 to 8%). Primary or secondary
      resistance of Pseudomonas aeruginosa was detected in 19% of the patients treated
      with cefepime and 44% of the patients treated with imipenem-cilastatin (P =
      0.05). Adverse events were reported in 71 of 138 (51%) and 62 of 141 (44%)
      patients eligible for safety analysis in the cefepime and imipenem groups,
      respectively (P = 0.23). Although the primary end point for this study does not
      exclude the possibility that cefepime was inferior to imipenem, some secondary
      analyses showed that the two regimens had comparable clinical and microbiological
      efficacies. Cefepime appeared to be less active against organisms producing an
      ESBL, but primary and secondary resistance to imipenem was more common for P.
      aeruginosa. Selection of a single agent for therapy of nosocomial pneumonia
      should be guided by local resistance patterns.

PMID- 14576101
TI  - Pharmacology of novel heteroaromatic polycycle antibacterials.
AB  - Heteroaromatic polycycle (HARP) compounds are a novel class of small (M(w), 600
      to 650) DNA-binding antibacterials. HARP compounds exhibit a novel mechanism of
      action by preferentially binding to AT-rich sites commonly found in bacterial
      promoters and replication origins. Noncovalent binding in the minor groove of DNA
      results in inhibition of DNA replication and DNA-dependent RNA transcription and
      subsequent bacterial growth. HARP compounds have previously been shown to have
      potent in vitro activities against a broad spectrum of gram-positive organisms.
      The present report describes the extensive profiling of the in vitro and in vivo
      pharmacology of HARP antibacterials. The efficacies of representative compounds
      (GSQ-2287, GSQ-10547, and GSQ-11203), which exhibited good MIC activity, were
      tested in murine lethal peritonitis and neutropenic thigh infection models
      following intravenous (i.v.) administration. All compounds were efficacious in
      vivo, with potencies generally correlating with MICs. GSQ-10547 was the most
      potent compound in vitro and in vivo, with a 50% effective dose in the murine
      lethal peritonitis model of 7 mg/kg of body weight against methicillin-sensitive
      Staphylococcus aureus (MSSA) and 13 mg/kg against methicillin-resistant S. aureus
      (MRSA). In the neutropenic mouse thigh infection model, GSQ-11203 reduced the
      bacterial load (MRSA and MSSA) 2 log units following administration of a 25-mg/kg
      i.v. dose. In a murine lung infection model, treatment with GSQ-10547 at a dose
      of 50 mg/kg resulted in 100% survival. In addition to determination of efficacy
      in animals, the pharmacokinetic and tissue disposition profiles in animals
      following administration of an i.v. dose were determined. The compounds were
      advanced into broad safety screening studies, including screening for safety
      pharmacology, genotoxicity, and rodent toxicity. The results support further
      development of this novel class of antibiotics.

PMID- 14576102
TI  - Quinine pharmacokinetic-pharmacodynamic relationships in uncomplicated falciparum
      malaria.
AB  - The relationships between the pharmacokinetic properties of quinine during a 7
      day treatment course and the therapeutic response were studied in 30 adult
      patients with uncomplicated falciparum malaria monitored for > or = 28 days. All
      patients received a 7-day oral quinine regimen either alone (n = 22) or in
      combination with rifampin (n = 8). The median fever clearance time was 58.5 h,
      and the mean +/- standard deviation parasite clearance time was 73 +/- 24 h.
      After recovery, six patients had recrudescences of Plasmodium falciparum malaria
      and seven had delayed appearances of P. vivax infection between days 16 and 23.
      Between the patients with and without recrudescences, there were no significant
      differences either in fever clearance time or parasite clearance time or in the
      overall pharmacokinetics of quinine and 3-hydroxyquinine. Patients for whom the
      area under the concentration-time curve from 3 to 7 days for quinine in plasma
      was <20 microg.day/ml had a relative risk of 5.3 (95% confidence interval = 1.6
      to 17.7) of having a subsequent recrudescence of infection (P = 0.016). Modeling
      of these data suggested an average minimum parasiticidal concentration of quinine
      in plasma of 3.4 microg/ml and an MIC of 0.7 microg/ml for uncomplicated
      falciparum malaria in Thailand. To ensure a cure, the minimum parasiticidal
      concentration must be exceeded during four asexual cycles (>6 days).

PMID- 14576103
TI  - Chloramphenicol is a potent inhibitor of cytochrome P450 isoforms CYP2C19 and
      CYP3A4 in human liver microsomes.
AB  - The inhibitory effect of chloramphenicol on human cytochrome P450 (CYP) isoforms
      was evaluated with human liver microsomes and cDNA-expressed CYPs.
      Chloramphenicol had a potent inhibitory effect on CYP2C19-catalyzed S-mephytoin
      4'-hydroxylation and CYP3A4-catalyzed midazolam 1-hydroxylation, with apparent
      50% inhibitory concentrations (inhibitory constant [K(i)] values are shown in
      parentheses) of 32.0 (7.7) and 48.1 (10.6) microM, respectively. Chloramphenicol
      also weakly inhibited CYP2D6, with an apparent 50% inhibitory concentration
      (K(i)) of 375.9 (75.8) microM. The mechanism of the drug interaction reported
      between chloramphenicol and phenytoin, which results in the elevation of plasma
      phenytoin concentrations, is clinically assumed to result from the inhibition of
      CYP2C9 by chloramphenicol. However, using human liver microsomes and cDNA
      expressed CYPs, we showed this interaction arises from the inhibition of CYP2C19-
      not CYP2C9-catalyzed phenytoin metabolism. In conclusion, inhibition of CYP2C19
      and CYP3A4 is the probable mechanism by which chloramphenicol decreases the
      clearance of coadministered drugs, which manifests as a drug interaction with
      chloramphenicol.

PMID- 14576104
TI  - Antiviral activity of RhoA-derived peptides against respiratory syncytial virus
      is dependent on formation of peptide dimers.
AB  - A synthetic peptide containing amino acids 77 to 95 of the intracellular GTPase
      RhoA has previously been shown to inhibit replication of respiratory syncytial
      virus (RSV) in cultured cells. We show that residues 80 to 90 of RhoA are
      sufficient for this activity and that the cysteine residue at position 83 is
      critical. Further studies with an optimal peptide sequence containing amino acids
      80 to 94 of RhoA revealed that the antiviral potency of the peptide is dependent
      on the oxidation of cysteine 83. Size-exclusion chromatography and sedimentation
      equilibrium studies of the peptide comprising residues 80 to 94 revealed that it
      is capable of forming aggregates in both reduced and oxidized states. A peptide
      (83A) in which the cysteine residue is replaced by an alanine does not form
      dimers or higher-order aggregates and did not inhibit RSV replication at any
      concentration tested. These data indicate that formation of peptide multimers is
      necessary for the antiviral activities of RhoA-derived peptides and suggest that
      the observed antiviral activities of these peptides may be unrelated to the
      biological functions of their parent molecule.

PMID- 14576105
TI  - Tenofovir resistance and resensitization.
AB  - Human immunodeficiency viruses in 321 samples from tenofovir-naive patients were
      retrospectively evaluated for resistance to this nucleotide analogue. All virus
      strains with insertions between amino acids 67 and 70 of the reverse
      transcriptase (n = 6) were highly resistant. Virus strains with the Q151M
      mutation were divided into susceptible (n = 12) and highly resistant (n = 8)
      viruses. This difference was due to the absence or presence of the K65R mutation,
      which was confirmed by site-directed mutagenesis. Viral clones with various
      combinations of the mutations M41L, K70R, L210W, and T215F or T215Y were analyzed
      for cross-resistance induced by thymidine analogue mutations (TAMs). The levels
      of increased resistance induced by single, double, and triple mutations at the
      indicated positions could be ranked as follows: for mutants with single
      mutations, mutations at positions 41 > 215 > 70; for mutants with double
      mutations, mutations at positions 41 and 215 > 70 and 215 = 210 and 215 > 41 and
      70; for mutants with triple mutations, mutations at positions 41, 210, and 215 >
      41, 70, and 215. Viral clones with M184V or M184I exhibited slightly increased
      susceptibilities to tenofovir (0.7-fold). Almost all clones with TAM-induced
      resistance were resensitized when M184V was present (P < 0.001). Among the
      viruses in the clinical samples, the rate of tenofovir resistance significantly
      increased with the number of TAMs both in the samples with 184M and in those with
      184V (P = 0.005 and P = 0.003, respectively). A resensitizing effect of M184V was
      confirmed for all samples exhibiting at least one TAM (P = 0.03). However,
      accumulation of at least two TAMs resulted in more than 2.0-fold reduced
      susceptibility to tenofovir, irrespective of the presence of M184V. Decision tree
      building, a classical machine learning technique, was used to generate models for
      the interpretation of mutations with respect to tenofovir resistance. The
      application of previously proposed cutoffs for a reduced response to therapy and
      treatment failure demonstrated the central roles of positions 215 and 65 for 1.5-
      and 4.0-fold reduced susceptibilities, respectively. Thus, clinically relevant
      resistance may be conferred by the accumulation of TAMs, and the resensitizing
      effect of M184V should be considered only minor.

PMID- 14576106
TI  - Controlled expression of an rpoS antisense RNA can inhibit RpoS function in
      Escherichia coli.
AB  - We show that an inducible rpoS antisense RNA complementary to the rpoS message
      can inhibit expression of RpoS in both exponential and stationary phases and can
      attenuate expression of the rpoS regulon in Escherichia coli. Plasmids containing
      rpoS antisense DNA expressed under the control of the T7lac promoter and T7 RNA
      polymerase were constructed, and expression of the rpoS antisense RNA was
      optimized in the pET expression system. rpoS antisense RNA levels could be
      manipulated to effectively control the expression of RpoS and RpoS-dependent
      genes. RpoS expression was inhibited by the expression of rpoS antisense RNA in
      both exponential and stationary phases in E. coli. RpoS-dependent catalase HPII
      was also downregulated, as determined by catalase activity assays and with native
      polyacrylamide gels stained for catalase. Induced RpoS antisense expression also
      reduced the level of RpoS-dependent glycogen synthesis. These results demonstrate
      that controlled expression of antisense RNA can be used to attenuate expression
      of a regulator required for the expression of host adaptation functions and may
      offer a basis for designing effective antimicrobial agents.

PMID- 14576107
TI  - In vitro activity and interaction of clindamycin combined with dihydroartemisinin
      against Plasmodium falciparum.
AB  - Combination regimens are considered a valuable tool for the fight against drug
      resistant falciparum malaria. This study was conducted to evaluate the
      antimalarial potential of clindamycin in combination with dihydroartemisinin in
      continuously cultured and in freshly isolated Plasmodium falciparum parasites,
      measuring the inhibition of Plasmodium falciparum histidine-rich protein II
      synthesis. Interaction analysis revealed a synergistic or additive mode of
      interaction at various concentration ratios in all continuously cultured
      parasites at the 50% effective concentration (EC(50)) level. Antagonism was not
      found for any of the culture-adapted parasites. In fresh P. falciparum isolates,
      a fixed clindamycin-dihydroartemisinin combination exhibited additive activity at
      the EC(50) and EC(90) levels. The drug mixture showed no significant activity
      correlation to other commonly used antimalarials. The clindamycin
      dihydroartemisinin combination appears to be a promising candidate for clinical
      investigation.

PMID- 14576108
TI  - pfcrt Allelic types with two novel amino acid mutations in chloroquine-resistant
      Plasmodium falciparum isolates from the Philippines.
AB  - Mutations in the pfcrt and pfmdr1 genes have been associated with chloroquine
      resistance in Plasmodium falciparum. Ten and five mutations, respectively, have
      been identified in these genes from chloroquine-resistant parasites worldwide.
      Mutation patterns in pfcrt revealed that chloroquine resistance evolved
      independently in southeast Asia, South America, and Papua New Guinea. However,
      the evolution of chloroquine resistance in the rest of the Pacific region is
      unclear. In this study, we examined sequence polymorphisms in these genes in
      isolates from Morong, Philippines, and compared them to known chloroquine
      resistance sequences. Two novel mutations, A144T and L160Y, were identified
      outside of the 10 known mutations in pfcrt in Morong isolates. These novel
      mutations were identified only in parasites with K76T and N326D but without the
      common A220S mutation found in most chloroquine-resistant isolates. This
      represents a unique chloroquine resistance allelic type (K76T/A144T/L160Y/N326D)
      not previously found elsewhere in the world. One Morong isolate also had an
      additional C72S mutation, whereas only one isolate possessed an allelic type
      typical of chloroquine resistance in Asia. Parasites with the novel pfcrt allelic
      types were resistant to chloroquine in vitro and were unresponsive to verapamil
      (0.9 microM) chemosensitization, similar to chloroquine-resistant parasites from
      South America and Papua New Guinea. These results suggest that chloroquine
      resistance evolved independently in the Philippines and represents a second
      chloroquine resistance founder event in the South Pacific.

PMID- 14576109
TI  - Extended-spectrum beta-lactamase-producing Enterobacteriaceae in community and
      private health care centers.
AB  - In 1999, 39 of 2,599 isolates of the family Enterobacteriaceae (1.5%) collected
      by eight private laboratories in the Aquitaine region in France produced an
      extended-spectrum beta-lactamase (ESBL). Among these were 19 Enterobacter
      aerogenes isolates; 8 Klebsiella pneumoniae isolates; 6 Escherichia coli
      isolates; 3 Proteus mirabilis isolates; and 1 isolate each of Serratia
      marcescens, Morganella morganii, and Providencia stuartii. ESBL producers were
      isolated from 38 patients, including 33 residents of 11 clinics or nursing homes
      and 5 ambulatory patients. Seven different ESBLs were characterized. These mainly
      consisted of TEM-24 (25 isolates) and TEM-21 (9 isolates), but TEM-15 (2
      isolates) and TEM-3, TEM-19, SHV-4, and CTX-M-1 (1 isolate each) were also
      characterized. Seven strains showed the coexistence of different TEM- and/or SHV
      encoding genes, including a new SHV-1 variant, SHV-44, defined by the
      substitution R205L previously reported for SHV-3 in association with S238G. The
      epidemiology of the ESBL producers was investigated by random amplification of
      polymorphic DNA, typing by enterobacterial repetitive intergenic consensus PCR,
      analysis of resistance cotransferred with the ESBL, and analysis of the
      restriction profiles of the ESBL-encoding plasmids. Of the TEM-24-expressing
      strains, 18 were E. aerogenes isolates, including 9 from the same clinic, that
      were representatives of the epidemic clone disseminating in France. Of the TEM-21
      producing strains that belonged to different species of the family
      Enterobacteriaceae (E. coli, K. pneumoniae, and P. mirabilis), 8 were isolated in
      the same nursing home. Outbreaks due to strain and/or plasmid dissemination in
      these clinic and nursing home were demonstrated. The presence of ESBL producers
      in five ambulatory patients probably resulted from nosocomial acquisition. Our
      data highlight the serious need to monitor patients for ESBL-producing
      Enterobacteriaceae in general practice.

PMID- 14576110
TI  - Influence of VanD type resistance on activities of glycopeptides in vitro and in
      experimental endocarditis due to Enterococcus faecium.
AB  - The consequences of VanD type glycopeptide resistance on the activity of
      vancomycin and teicoplanin were evaluated in vitro and in a rabbit model of
      aortic endocarditis with VanD type clinical isolate Enterococcus faecium BM4339
      (MICs: vancomycin, 64 microg/ml; teicoplanin, 4 microg/ml) and its susceptible
      derivative BM4459 (MICs: vancomycin, 1 microg/ml; teicoplanin, 1 microg/ml). The
      two antibiotics were inactive against BM4339 in vivo, in terms both of reduction
      of bacterial counts and of prevention of emergence of glycopeptide-resistant
      subpopulations, despite using teicoplanin at concentrations greater than the MIC
      for VanD strains. This could be due to the high inoculum effect also observed in
      vitro with BM4339 and two other VanD type isolates against both antibiotics.
      These results suggest that detection of VanD type resistance is of major
      importance because it abolishes in vivo glycopeptide activity and allows the
      emergence of mutants highly resistant to glycopeptides.

PMID- 14576111
TI  - Tylosin resistance in Arcanobacterium pyogenes is encoded by an erm X
      determinant.
AB  - Arcanobacterium pyogenes, a commensal on the mucous membranes of many
      economically important animal species, is also a pathogen, causing abscesses of
      the skin, joints, and visceral organs as well as mastitis and abortion. In food
      animals, A. pyogenes is exposed to antimicrobial agents used for growth
      promotion, prophylaxis, and therapy, notably tylosin, a macrolide antibiotic used
      extensively for the prevention of liver abscessation in feedlot cattle in the
      United States. Of 48 A. pyogenes isolates, 11 (22.9%) exhibited inducible or
      constitutive resistance to tylosin (MIC of > or = 128 microg/ml). These isolates
      also exhibited resistance to other macrolide and lincosamide antibiotics,
      suggesting a macrolide-lincosamide resistance phenotype. Of the 11 resistant
      isolates, genomic DNA from nine hybridized to an erm(X)-specific probe. Cloning
      and nucleotide sequencing of the A. pyogenes erm(X) gene indicated that it was
      >95% similar to erm(X) genes from Corynebacterium and Propionibacterium spp.
      Eight of the erm(X)-containing A. pyogenes isolates exhibited inducible tylosin
      resistance, which was consistent with the presence of a putative leader peptide
      upstream of the erm(X) open reading frame. For at least one A. pyogenes isolate,
      98-4277-2, erm(X) was present on a plasmid, pAP2, and was associated with the
      insertion sequence IS6100. pAP2 also carried genes encoding the repressor
      regulated tetracycline efflux system determinant Tet 33. The repA gene from pAP2
      was nonfunctional in Escherichia coli and at least one A. pyogenes isolate,
      suggesting that there may be host-encoded factors required for replication of
      this plasmid.

PMID- 14576112
TI  - Resistance profile of a hepatitis C virus RNA-dependent RNA polymerase
      benzothiadiazine inhibitor.
AB  - Recently, a benzo-1,2,4-thiadiazine antiviral agent (C(21)H(21)N(3)O(4)S;
      compound 4) was shown to be a potent, highly specific inhibitor of the primary
      catalytic enzyme of the hepatitis C virus (HCV) replicase complex. In this study,
      we selected for resistance to confirm the mechanism of action for compound 4 in
      HCV replicon cells. As expected, spontaneous mutations or fluidity in the HCV
      polymerase (NS5B) coding sequence occurred upon routine passage of the HCV
      replicon cells in the absence of compound 4. After 1 month of culture in the
      presence of 10 microM compound 4, or 20 times the 50% inhibitory concentration of
      the replicon, replicon cells were almost 20-fold less susceptible to compound 4.
      Twenty-one NS5B cDNA clones were generated from the resistant replicon cells.
      Five mutations in the 21 NS5B clones were present at frequencies higher than that
      of control replicon cells, and no clone contained more than a single mutation
      within the polymerase gene. RNA-dependent RNA polymerase studies using purified
      recombinant NS5B containing these single point mutations allowed the
      identification of residue 414 as sufficient for biochemical resistance to
      compound 4. Further, the contribution of this residue to confer cell-based
      resistance to compound 4 was validated using a stable recombinant mutant replicon
      cell line which harbors a methionine-to-threonine change at residue 414. The
      potential for additional mutations in other nonstructural genes of HCV to
      contribute to the resistance profile of compound 4 is discussed.

PMID- 14576113
TI  - Effects of triclosan-containing rinse on the dynamics and antimicrobial
      susceptibility of in vitro plaque ecosystems.
AB  - Dental plaque microcosms were established under a feast-famine regimen within
      constant-depth film fermentors and exposed four times daily postfeeding to a
      triclosan (TR)-containing rinse (dentifrice) (TRD). This was diluted so that the
      antimicrobial content was 0.6 mg/ml. Microcosms were characterized by
      heterotrophic plate counts and PCR-denaturing gradient gel electrophoresis (DGGE)
      with primers specific for the V2-V3 region of the eubacterial 16S rRNA gene
      (rDNA). Dominant isolates and PCR amplicons were identified by partial sequencing
      of 16S rDNA. TRD caused considerable decreases in the counts of both gram
      negative organisms and total anaerobic cells, transiently lowered the numbers of
      streptococci and actinomycetes, and markedly increased the proportion of
      lactobacilli. DGGE indicated the presence of putatively unculturable bacteria and
      showed that a Porphyromonas sp. and Selenomonas infelix had been inhibited by
      TRD. Pure culture studies of 10 oral bacteria (eight genera) showed that
      Neisseria subflava, Prevotella nigrescens, and Porphyromonas gingivalis were
      highly susceptible to TR, while the lactobacilli and streptococci were the least
      susceptible. Clonal expansion of the lactobacilli in the pulsed microcosm could
      be explained on the basis of TR activity. The mean MICs of TR, chlorhexidine,
      erythromycin, penicillin V, and vancomycin for the population before and after 5
      days of exposure to TRD showed few significant changes. In conclusion, changes in
      plaque microcosm populations following repeated exposure to TRD showed inhibition
      of the most susceptible flora and clonal expansion of less susceptible species.

PMID- 14576114
TI  - In vitro activities of garenoxacin (BMS-284756) against Haemophilus influenzae
      isolates with different fluoroquinolone susceptibilities.
AB  - The in vitro activity of garenoxacin (BMS-284756) against 62 clinical Haemophilus
      influenzae isolates with different fluoroquinolone susceptibilities was
      determined by the microdilution susceptibility testing method and compared with
      the activities of other oral quinolones and nonquinolone oral antimicrobial
      agents. Cefixime presented the highest intrinsic activity (MIC at which 50% of
      the isolates tested were inhibited [MIC(50)], 0.01 microg/ml), followed by
      garenoxacin, moxifloxacin, and ciprofloxacin (MIC(50), 0.06 microg/ml),
      levofloxacin (MIC(50), 0.12 microg/ml), cefuroxime (MIC(50), 1.0 microg/ml), and
      amoxicillin-clavulanate (MIC(50), 1.0/0.5 microg/ml), amoxicillin (MIC(50), 2
      microg/ml), azithromycin (MIC(50), 4 microg/ml), and erythromycin (MIC(50), 8
      microg/ml). In strains with ciprofloxacin MICs of < or =0.06 microg/ml,
      ciprofloxacin and garenoxacin displayed similar MIC(50)s and MIC(90)s, one
      dilution lower than those of moxifloxacin and levofloxacin. For strains for which
      ciprofloxacin MICs were > or = 0.12 microg/ml, MIC(50)s were similar for the four
      quinolones tested, although garenoxacin presented the widest activity range (0.03
      to 32 microg/ml) and the highest MIC at which 90% of the isolates tested were
      inhibited (16.0 microg/ml). For strains without amino acid changes in the
      quinolone resistance determining region (QRDR) of GyrA and ParC, garenoxacin MICs
      were < or =0.03 microg/ml; with a single amino acid change in GyrA, garenoxacin
      MICs were 0.06 to 0.12 microg/ml; with one amino acid change each in GyrA and
      ParC, garenoxacin MICs were 0.5 to 2.0 micro g/ml; one amino acid change in ParC
      combined with two amino acid changes in GyrA increased the MICs to > or = 4
      microg/ml for all assayed quinolones. We conclude that garenoxacin has excellent
      activity against H. influenzae, although progressive acquired resistance was
      observed by step-by-step mutation in the QRDR of gyrA and parC.

PMID- 14576115
TI  - In vitro activities of garenoxacin (BMS-284756) against Streptococcus pneumoniae,
      viridans group streptococci, and Enterococcus faecalis compared to those of six
      other quinolones.
AB  - The activity of garenoxacin, a new quinolone, was determined in comparison with
      other quinolones against different strains of S. pneumoniae, viridans group
      streptococci (VGS), and Enterococcus faecalis. Strains were quinolone-susceptible
      clinical isolates and quinolone-resistant strains with defined mechanisms of
      resistance obtained from either clinical isolates or derivatives of S. pneumoniae
      R6. Clinical quinolone-susceptible strains of S. pneumoniae, VGS and E. faecalis
      showed garenoxacin MICs within a range of 0.03 microg/ml to 0.25 micro g/ml.
      Garenoxacin MICs increased two- to eightfold when one mutation was present in the
      ParC quinolone resistance-determining region (QRDR), fourfold when one mutation
      was present in the GyrA QRDR (S. pneumoniae), 8- to 64-fold when two or three
      mutations were associated in ParC and GyrA QRDR, and 2,048-fold when two
      mutations were present in both the GyrA and ParC QRDRs (Streptococcus
      pneumoniae). Increased active efflux had a moderate effect on garenoxacin MICs
      for S. pneumoniae and VGS. Against S. pneumoniae, garenoxacin behaved like
      moxifloxacin and sparfloxacin, being more affected by a single gyrA mutation than
      by a single parC mutation. Although garenoxacin was generally two- to fourfold
      more active than moxifloxacin against the different wild-type or mutant strains
      of S. pneumoniae, VGS, and E. faecalis, it was two- to fourfold less active than
      gemifloxacin. At four times the respective MIC for each strain, the bactericidal
      effect of garenoxacin, observed at 6 h for S. pneumoniae and at 24 h for S.
      oralis and E. faecalis, was not influenced by the presence of mutation either in
      the ParC or in both the ParC and GyrA QRDRs.

PMID- 14576116
TI  - Relevance of soft-tissue penetration by levofloxacin for target site bacterial
      killing in patients with sepsis.
AB  - Antimicrobial therapy of soft tissue infections in patients with sepsis sometimes
      lacks efficiency, despite the documented susceptibility of the causative pathogen
      to the administered antibiotic. In this context, impaired equilibration between
      the antibiotic concentrations in plasma and those in tissues in critically ill
      patients has been discussed. To characterize the impact of tissue penetration of
      anti-infective agents on antimicrobial killing, we used microdialysis to measure
      the concentration-versus-time profiles of levofloxacin in the interstitial space
      fluid of skeletal muscle in patients with sepsis. Subsequently, we applied an
      established dynamic in vivo pharmacokinetic-in vitro pharmacodynamic approach to
      simulate bacterial killing at the site of infection. The population mean areas
      under the concentration-time curves (AUCs) for levofloxacin showed that
      levofloxacin excellently penetrates soft tissues, as indicated by the ratio of
      the AUC from time zero to 8 h (AUC(0-8)) for muscle tissue (AUC(0-8 muscle)) to
      the AUC(0-8) for free drug in plasma (AUC(0-8 plasma free)) (AUC(0-8
      muscle)/AUC(0-8 plasma free) ratio) of 0.85. The individual values of tissue
      penetration and maximum concentration (C(max)) in muscle tissue were highly
      variable. No difference in bacterial killing of a select Staphylococcus aureus
      strain for which the MIC was 0.5 microg/ml was found between individuals after
      exposure to dynamically changing concentrations of levofloxacin in plasma and
      tissue in vitro. In contrast, the decrease in the bacterial counts of Pseudomonas
      aeruginosa (MIC = 2 microg/ml) varied extensively when the bacteria were exposed
      to levofloxacin at the concentrations determined from the individual
      concentration-versus-time profiles obtained in skeletal muscle. The extent of
      bacterial killing could be predicted by calculating individual C(max)/MIC and
      AUC(0-8 muscle)/AUC(0-8 plasma free) ratios (R = 0.96 and 0.93, respectively). We
      have therefore shown in the present study that individual differences in the
      tissue penetration of levofloxacin may markedly affect target site killing of
      bacteria for which MICs are close to 2 microg/ml.

PMID- 14576117
TI  - Extended-spectrum beta-lactamases in Klebsiella pneumoniae bloodstream isolates
      from seven countries: dominance and widespread prevalence of SHV- and CTX-M-type
      beta-lactamases.
AB  - A huge variety of extended-spectrum beta-lactamases (ESBLs) have been detected
      during the last 20 years. The majority of these have been of the TEM or SHV
      lineage. We have assessed ESBLs occurring among a collection of 455 bloodstream
      isolates of Klebsiella pneumoniae, collected from 12 hospitals in seven
      countries. Multiple beta-lactamases were produced by isolates with phenotypic
      evidence of ESBL production (mean of 2.7 beta-lactamases per isolate; range, 1 to
      5). SHV-type ESBLs were the most common ESBL, occurring in 67.1% (49 of 73) of
      isolates with phenotypic evidence of ESBL production. In contrast, TEM-type ESBLs
      (TEM-10 type, -12 type, -26 type, and -63 type) were found in just 16.4% (12 of
      73) of isolates. The finding of TEM-10 type and TEM-12 type represents the first
      detection of a TEM-type ESBL in South America. PER (for Pseudomonas extended
      resistance)-type beta-lactamases were detected in five of the nine isolates from
      Turkey and were found with SHV-2-type and SHV-5-type ESBLs in two of the
      isolates. CTX-M-type ESBLs (bla(CTX-M-2) type and bla(CTX-M-3) type) were found
      in 23.3% (17 of 73) of isolates and were found in all study countries except for
      the United States. We also detected CTX-M-type ESBLs in four countries where they
      have previously not been described-Australia, Belgium, Turkey, and South Africa.
      The widespread emergence and proliferation of CTX-M-type ESBLs is particularly
      noteworthy and may have important implications for clinical microbiology
      laboratories and for physicians treating patients with serious K. pneumoniae
      infections.

PMID- 14576118
TI  - Analysis of daptomycin efficacy and breakpoint standards in a murine model of
      Enterococcus faecalis and Enterococcus faecium renal infection.
AB  - Daptomycin efficacy against clinical isolates of Enterococcus faecalis,
      Enterococcus faecium, and a lab-derived daptomycin-resistant isolate of E.
      faecalis was investigated in a mouse model of renal infection. The daptomycin
      MICs against these enterococci ranged from 0.5 to 50 micro g/ml. The objective of
      this study was to determine the relationship between the MICs of drugs against E.
      faecalis and E. faecium and the level of daptomycin exposure needed to evaluate
      the drug's efficacy. Correlating the required therapeutic exposures of mice with
      the exposures achieved clinically allowed us to project enterococcal breakpoint
      values. Mice pretreated with carrageenan were infected intravenously with 3 x
      10(8) to 4 x 10(8) CFU of E. faecalis or E. faecium. Daptomycin (5 to 50 mg of
      drug/kg of body weight) or saline control was administered 4 h postinfection and
      continued once daily for 2 days (three total doses). On day 4, infected kidneys
      were harvested, homogenized, and dilution plated. Efficacy was defined as a > or
      = 2-log(10) (99%) reduction in bacterial burden in infected kidneys. At
      clinically relevant dosages and exposures (area under the curve, 400 to 600
      microg.hr/ml), daptomycin demonstrated similar and marked efficacy against all
      clinical enterococcal isolates tested. Daptomycin achieved efficacy with
      comparable doses against both vancomycin-sensitive (MIC, < or = 4 microg/ml) and 
      resistant enterococcal strains tested. Efficacy was also established against the
      lab-derived daptomycin-resistant E. faecalis isolate. In this murine renal
      infection model, clinically relevant exposures of daptomycin were effective
      against E. faecalis and E. faecium strains for which MICs were < or = 8
      microg/ml. These murine efficacy data for daptomycin, along with surveillance
      data and human pharmacokinetic exposures achieved, suggest a breakpoint
      concentration value of < or = 8 microg/ml (susceptible) and > or = 16 microg/ml
      (resistant) for daptomycin against E. faecium and E. faecalis.

PMID- 14576119
TI  - Mutations in topoisomerase genes of fluoroquinolone-resistant salmonellae in Hong
      Kong.
AB  - A total of 88 salmonella isolates (72 clinical isolates for which the
      ciprofloxacin MIC was >0.06 microg/ml, 15 isolates for which the ciprofloxacin
      MIC was < or =0.06 microg/ml, and Salmonella enterica serotype Typhimurium ATCC
      13311) were studied for the presence of genetic alterations in four quinolone
      resistance genes, gyrA, gyrB, parC, and parE, by multiplex PCR amplimer
      conformation analysis. The genetic alterations were confirmed by direct
      nucleotide sequencing. A considerable number of strains had a mutation in parC,
      the first to be reported in salmonellae. Seven of the isolates sensitive to 0.06
      micro g of ciprofloxacin per ml had a novel mutation at codon 57 of parC (Tyr57-
      >Ser) which was also found in 29 isolates for which ciprofloxacin MICs were >0.06
      micro g/ml. Thirty-two isolates had a single gyrA mutation (Ser83-->Phe, Ser83-
      >Tyr, Asp87-->Asn, Asp87-->Tyr, or Asp87-->Gly), 34 had both a gyrA mutation and
      a parC mutation (29 isolates with a parC mutation of Tyr57-->Ser and 5 isolates
      with a parC mutation of Ser80-->Arg). Six isolates which were isolated recently
      (from 1998 to 2001) were resistant to 4 micro g of ciprofloxacin per ml. Two of
      these isolates had double gyrA mutations (Ser83-->Phe and Asp87-->Asn) and a parC
      mutation (Ser80-->Arg) (MICs, 8 to 32 microg/ml), and four of these isolates had
      double gyrA mutations (Ser83-->Phe and Asp87-->Gly), one parC mutation (Ser80-
      >Arg), and one parE mutation (Ser458-->Pro) (MICs, 16 to 64 micro g/ml). All six
      of these isolates and those with a Ser80-->Arg parC mutation were S. enterica
      serotype Typhimurium. One S. enterica serotype Typhi isolate harbored a single
      gyrA mutation (Ser83-->Phe), and an S. enterica serotype Paratyphi A isolate
      harbored a gyrA mutation (Ser83-->Tyr) and a parC mutation (Tyr57-->Ser); both of
      these isolates had decreased susceptibilities to the fluoroquinolones. The MICs
      of ciprofloxacin, levofloxacin, and sparfloxacin were in general the lowest of
      those of the six fluoroquinolones tested. Isolates with a single gyrA mutation
      were less resistant to fluoroquinolones than those with an additional parC
      mutation (Tyr57-->Ser or Ser80-->Arg), while those with double gyrA mutations
      were more resistant.

PMID- 14576120
TI  - Related clones containing SCCmec type IV predominate among clinically significant
      Staphylococcus epidermidis isolates.
AB  - SCCmec is a mobile genetic element that carries the gene (mecA) mediating
      methicillin resistance in staphylococci. For Staphylococcus aureus, four SCCmec
      types have been described, one (type IV) of which has been associated with newly
      identified community-acquired methicillin-resistant S. aureus. However, the
      distribution of SCCmec types among S. epidermidis is not known. SCCmec typing of
      a collection of 44 methicillin-resistant Staphylococcus epidermidis (MRSE)
      isolates recovered between 1973 and 1983 from the blood of patients with
      prosthetic valve endocarditis (PVE) was performed by PCR amplification of key
      genetic elements (mecA, mecI, IS1272, and ccrAB). Of the 44 isolates, 1 (2%)
      harbored SCCmec type I, 15 (34%) harbored type II, 12 (28%) harbored type III,
      and 16 (36%) harbored type IV. The complete nucleotide sequence of SCCmec type IV
      was determined for 16 isolates and found to be identical in size (24 kb) and 98%
      homologous to DNA sequences published for S. aureus. Type IV SCCmec was also
      common (5 of 10 isolates) among a geographically dispersed collection of 10
      recent (1998 to 2001) S. epidermidis bloodstream isolates. Multilocus sequence
      typing (MLST) (using the same seven genes presently employed for S. aureus MLST)
      of these MRSE isolates and of 10 additional recent geographically dispersed
      methicillin-susceptible isolates demonstrated that all 16 PVE isolates and 2 of 5
      recent isolates harboring type IV SCCmec were in three related clonal groups. All
      three MSSE PVE isolates recovered from patients between 1976 and 1979 were in the
      same clonal groups as type IV SCCmec MRSE isolates. These data support the
      hypothesis of intra- and interspecies transfer of type IV SCCmec and suggest that
      there are clonal associations in S. epidermidis that correlate with SCCmec type.

PMID- 14576121
TI  - In vitro and ex vivo activities of minocycline and EDTA against microorganisms
      embedded in biofilm on catheter surfaces.
AB  - Minocycline-EDTA (M-EDTA) flush solution has been shown to prevent catheter
      related infection and colonization in a rabbit model and in hemodialysis
      patients. We undertook this study in order to determine the activities of M-EDTA
      against organisms embedded in fresh biofilm (in vitro) and mature biofilm (ex
      vivo). For the experiment with the in vitro model, a modified Robbin's device
      (MRD) was used whereby 25 catheter segments were flushed for 18 h with 10(6) CFU
      of biofilm-producing Staphylococcus epidermidis, Staphylococcus aureus, and
      Candida albicans per ml. Subsequently, each of the catheter segments was
      incubated in one of the following solutions: (i) streptokinase, (ii) heparin,
      (iii) broth alone, (iv) vancomycin, (v) vancomycin-heparin, (vi) EDTA, (vii)
      minocycline (high-dose alternating with low-dose), or (viii) M-EDTA (low-dose
      minocycline alternating with high-dose minocycline were used to study the
      additive and synergistic activities of M-EDTA). All segments were cultured
      quantitatively by scrape sonication. For the experiment with the ex vivo model,
      54 catheter tip segments removed from patients and colonized with bacterial
      organisms by roll plate were longitudinally cut into two equal segments and
      exposed to either saline, heparin, EDTA, or M-EDTA (with high-dose minocycline).
      Subsequently, all segments were examined by confocal laser electron microscopy.
      In the in vitro MRD model, M-EDTA (with a low concentration of minocycline) was
      significantly more effective than any other agent in reducing colonization of S.
      epidermidis, S. aureus, and C. albicans (P < 0.01). M-EDTA (with a high
      concentration of minocycline) eradicated all staphylococcal and C. albicans
      organisms embedded in the biofilm. In the ex vivo model, M-EDTA (with a high
      concentration of minocycline) reduced bacterial colonization more frequently than
      EDTA or heparin (P < 0.01). We concluded that M-EDTA is highly active in
      eradicating microorganisms embedded in fresh and mature biofilm adhering to
      catheter surfaces.

PMID- 14576122
TI  - Salvage treatment with amphotericin B in progressive human alveolar
      echinococcosis.
AB  - Most patients with alveolar echinococcosis are diagnosed at a late stage when the
      disease has advanced to unresectable hepatic lesions. These patients require
      lifelong therapy with benzimidazoles, the only medical treatment currently
      available. To date, no treatment option remains for patients with benzimidazole
      intolerance or treatment failure. Amphotericin B was recently shown to exert
      antiparasitic activity in vitro. Here, we report the efficacy of amphotericin B
      in human alveolar echinococcosis. In three patients with extensive disease and
      without further treatment options, disease progression had been documented over
      several months. They were treated with amphotericin B intravenously at a dose of
      0.5 mg/kg of body weight three times per week. Follow-up parameters were physical
      examination, laboratory parameters, and imaging techniques. Amphotericin B
      treatment effectively halted parasite growth in all three patients. The
      antiparasitic effect was most evident by spontaneous closure of cutaneous
      fistulae in two patients and by constant size of parasitic lesions during
      treatment, as assessed radiologically. Metabolic activity in parasitic areas was
      visualized by positron emission tomography and significantly decreased during
      treatment. However, progressive affection of the heart in one patient could not
      be stopped. All patients currently continue on amphotericin B and have been
      treated for 25, 17, and 14 months, respectively. We introduce amphotericin B as
      salvage treatment for alveolar echinococcosis patients with intolerance or
      resistance to benzimidazoles, as it effectively suppresses parasite growth.
      Amphotericin B is not parasitocidal; therefore long-term treatment has to be
      anticipated.

PMID- 14576123
TI  - Attenuation of itraconazole fungicidal activity following preexposure of
      Aspergillus fumigatus to fluconazole.
AB  - Fluconazole (FLC), a triazole with limited activity against Aspergillus species,
      is frequently used as prophylaxis in leukemia patients and bone marrow transplant
      recipients. Prior FLC use has been associated with an increasing incidence of
      invasive aspergillosis in these patients. We hypothesized that prior exposure of
      Aspergillus fumigatus to FLC could result in altered in vitro susceptibility of
      this fungus to other, more active triazoles. Thus, we performed serial passages
      of conidia of 10 clinical isolates of A. fumigatus (all itraconazole [ITC]
      susceptible) on FLC-containing yeast agar glucose plates. The MICs and minimal
      fungicidal concentrations (MFCs) of amphotericin B, FLC, ITC, and voriconazole
      (VRC) for A. fumigatus conidia were measured following four passages on FLC
      containing medium according to the National Committee for Clinical Laboratory
      Standards microdilution method. Serial passages on FLC-containing plates resulted
      in a fourfold increase in the MFCs (but not the MICs) of ITC for nine isolates.
      The attenuated ITC fungicidal activity against A. fumigatus following FLC
      preexposure was medium independent and was also observed against FLC-preexposed
      A. fumigatus hyphae with the viability staining FUN-1 dye. Moreover, FLC
      preexposure of A. fumigatus conidia resulted in an analogous increase in the MFCs
      (but not the MICs) of VRC. Our findings suggest that preexposure of A. fumigatus
      to FLC attenuates the in vitro fungicidal activity of subsequent ITC use against
      it. This phenotypic adaptation is not captured by a routine MIC determination but
      requires MFC measurement. The in vivo significance of this in vitro phenomenon
      requires further investigation.

PMID- 14576125
TI  - In vitro activity of TD-6424 against Staphylococcus aureus.
AB  - TD-6424, a rapidly bactericidal agent with multiple mechanisms of action, is more
      potent in vitro and more rapidly bactericidal than currently available agents
      against methicillin-susceptible and methicillin-resistant Staphylococcus aureus.
      TD-6424 produces a postantibiotic effect with a duration of 4 to 6 h against
      these organisms. The results suggest potential efficacy against susceptible and
      resistant strains of S. aureus.

PMID- 14576124
TI  - Active internalization of the Penicillium chrysogenum antifungal protein PAF in
      sensitive aspergilli.
AB  - The Penicillium chrysogenum antifungal protein PAF inhibits the growth of various
      filamentous fungi. In this study, PAF was found to localize to the cytoplasm of
      sensitive aspergilli by indirect immunofluorescence staining. The internalization
      process required active metabolism and ATP and was prevented by latrunculin B,
      suggesting an endocytotic mechanism.

PMID- 14576126
TI  - First Streptococcus agalactiae isolates highly resistant to quinolones, with
      point mutations in gyrA and parC.
AB  - Three isolates of Streptococcus agalactiae highly resistant to multiple
      fluoroquinolones were isolated in Japan. Compared with susceptible strains of S.
      agalactiae, these quinolone-resistant strains had double point mutations within
      the quinolone resistance-determining regions of gyrA and parC; Ser-81 was changed
      to Leu (TCA --> TTA) in the amino acid sequence deduced from gyrA, and Ser-79 was
      changed to Phe (TCC --> TTC) in the amino acid sequence deduced from parC.
      Comparative sequence analysis revealed the possibility of gene transfer between
      S. agalactiae and another beta-hemolytic streptococcus, Streptococcus difficile.

PMID- 14576127
TI  - Effect of parenteral antibiotic administration on establishment of intestinal
      colonization in mice by Klebsiella pneumoniae strains producing extended-spectrum
      beta-lactamases.
AB  - A mouse model was used to test the hypothesis that antibiotics with activity
      against anaerobes promote overgrowth of extended-spectrum beta-lactamase
      producing Klebsiella pneumoniae strains in stool. Subcutaneous clindamycin
      consistently promoted establishment of high-density colonization, whereas
      piperacillin-tazobactam, ceftriaxone, and ceftazidime promoted colonization only
      when a large inoculum and/or more resistant strain was administered.

PMID- 14576128
TI  - In vitro activity of recombinant lysostaphin against Staphylococcus aureus
      isolates from anterior nares and blood.
AB  - The in vitro activity of recombinant lysostaphin was tested against a collection
      of well-characterized clinical Staphylococcus aureus isolates by disk diffusion
      (429 isolates) and minimum bactericidal concentration (10 isolates) assays.
      Minimum bactericidal concentrations of 0.16 microg/ml and zones of inhibition
      ranging between 15 and 21 mm in diameter demonstrate that lysostaphin was highly
      active against all isolates tested.

PMID- 14576129
TI  - Resazurin microtiter assay plate testing of Mycobacterium tuberculosis
      susceptibilities to second-line drugs: rapid, simple, and inexpensive method.
AB  - The emergence of multidrug-resistant tuberculosis calls for new, rapid drug
      susceptibility tests. We have tested 150 Mycobacterium tuberculosis isolates
      against the second-line drugs ethionamide, kanamycin, capreomycin, ofloxacin, and
      para-aminosalicylic acid by the colorimetric resazurin microtiter assay and the
      proportion method. By visual reading, MICs were obtained after 8 days. A very
      good correlation between results by the colorimetric resazurin microtiter assay
      and the proportion method was obtained. The colorimetric resazurin microtiter
      assay is inexpensive, rapid, and simple to perform, and implementation of the
      assay is feasible for low-resource countries.

PMID- 14576130
TI  - Rapid detection and estimation by pyrosequencing of 23S rRNA genes with a single
      nucleotide polymorphism conferring linezolid resistance in Enterococci.
AB  - Pyrosequencing was used to detect rapidly and estimate the number of 23S rRNA
      genes with a G2576T mutation in 43 linezolid-resistant and -susceptible clinical
      isolates of enterococci. The method showed 100% concordance with PCR-restriction
      fragment length polymorphism for detecting isolates homozygous for either G2576
      or T2576 or heterozygous for this mutation. A good correlation was found between
      linezolid MICs and the number of 23S rRNA gene copies carrying the mutation.

PMID- 14576132
TI  - Flow cytometry antifungal susceptibility testing of Aspergillus fumigatus and
      comparison of mode of action of voriconazole vis-a-vis amphotericin B and
      itraconazole.
AB  - Aspergillus fumigatus isolates were tested with three antifungals by flow
      cytometry (FC) and fluorescence-activated cell sorting. FC results after 4 h
      correlated well with MICs obtained by the NCCLS M38-A method; voriconazole
      exhibited fungicidal activity, albeit to a lesser extent than amphotericin B, but
      to a greater extent than itraconazole.

PMID- 14576131
TI  - R57K polymorphism in the human immunodeficiency virus type 1 protease as
      predictor of early virological failure in a cohort of antiretroviral-naive
      patients treated mostly with a nelfinavir-containing regimen.
AB  - In 243 antiretroviral-naive human immunodeficiency-infected patients starting a
      first-line-protease inhibitor (mainly nelfinavir)-containing therapy, the
      presence of the polymorphism R57K in the protease at the inception of therapy was
      independently associated with a higher rate of virological failure.

PMID- 14576133
TI  - Doxycycline is anti-inflammatory and inhibits staphylococcal exotoxin-induced
      cytokines and chemokines.
AB  - Proinflammatory cytokines mediate the toxic effect of superantigenic
      staphylococcal exotoxins (SE). Doxycycline inhibited SE-stimulated T-cell
      proliferation and production of cytokines and chemokines by human peripheral
      blood mononuclear cells. These results suggest that the antibiotic doxycycline
      has anti-inflammatory effects and is therapeutically useful for mitigating the
      pathogenic effects of SE.

PMID- 14576134
TI  - In vitro analysis of the ability of Trichophyton rubrum to become resistant to
      terbinafine.
AB  - In this study, we have investigated in vitro the resistance frequency and
      development of resistance to terbinafine of Trichophyton rubrum. Results
      demonstrated that naturally occurring mutants are rare and that T. rubrum appears
      to have little capacity to develop resistance to terbinafine even after prolonged
      exposure.

PMID- 14576135
TI  - Genetic relatedness of recently collected Spanish respiratory tract Streptococcus
      pneumoniae isolates with reduced susceptibility to amoxicillin.
AB  - Of Streptococcus pneumoniae isolates from 17 hospitals, 9.8% were amoxicillin
      nonsusceptible (MIC > or = 4 microg/ml). The genetic relatedness of 138 isolates
      was studied by pulsed-field gel electrophoresis. Although 44 different clones
      were detected, more than 62% of these isolates were related to four clones
      (Spain(23F)-1, Spain(6B)-2, Spain(9V)-3, and Spain(14)-5).

PMID- 14576136
TI  - Multiple-drug resistance in D-tartrate-positive Salmonella enterica serovar
      paratyphi B isolates from poultry is mediated by class 2 integrons inserted into
      the bacterial chromosome.
AB  - The presence of integrons in 85 multiresistant German isolates of the
      predominating Salmonella enterica subsp. enterica serovar Paratyphi B dT(+) clone
      was investigated. All isolates possessed a chromosomally located Tn7-like class 2
      integron carrying the same dfrA1-sat1-aadA1 array of gene cassettes. Only four
      isolates (4.7%) revealed an additional class 1 integron with two strains each
      containing the aadA1 or dfrA1-aadA1 gene cassettes.

PMID- 14576138
TI  - Activity of posaconazole in treatment of experimental disseminated zygomycosis.
AB  - Three isolates of zygomycetes were used to produce a disseminated infection in
      nonimmunocompromised mice. Against all zygomycete strains, amphotericin B
      significantly prolonged survival. Itraconazole was inactive against Rhizopus
      microsporus and Rhizopus oryzae but was partially active against Absidia
      corymbifera. Posaconazole had no beneficial effects against R. oryzae but showed
      partial activity against A. corymbifera. Posaconazole had a clear dose-response
      effect against R. microsporus.

PMID- 14576137
TI  - Favorable interactions between enfuvirtide and 1-beta-D-2,6-diaminopurine
      dioxolane in vitro.
AB  - We evaluated the in vitro anti-human immunodeficiency virus type 1 (HIV-1)
      interactions between 1-beta-D-2,6-diaminopurine dioxolane (DAPD) and enfuvirtide
      (T-20) against clinical isolates sensitive and resistant to reverse transcriptase
      and protease inhibitors. Interactions between T-20 and DAPD were synergistic to
      nearly additive, with combination index values ranging from 0.53 to 1.06 at 95%
      inhibitory concentrations. These studies suggest that a combination of T-20 and
      DAPD might be useful in the treatment of antiretroviral drug-experienced
      patients.

PMID- 14576139
TI  - Activity of AZD2563, a novel oxazolidinone, against Staphylococcus aureus strains
      with reduced susceptibility to vancomycin or linezolid.
AB  - The susceptibilities of clinical vancomycin-intermediate Staphylococcus aureus
      (VISA), heterogeneous VISA, and laboratory-generated linezolid-resistant S.
      aureus strains to the new oxazolidinone AZD2563 were assessed by agar dilution
      MIC determination. All clinical strains were susceptible to linezolid, and the
      linezolid MICs for them were equal to or twofold higher than those of AZD2563.
      Cross-resistance with linezolid was seen in laboratory-generated mutants, and for
      these strains the MIC of AZD2563 was twofold higher than that of linezolid.

PMID- 14576140
TI  - G484S amino acid substitution in lanosterol 14-alpha demethylase (ERG11) is
      related to fluconazole resistance in a recurrent Cryptococcus neoformans clinical
      isolate.
AB  - Five sequential Cryptococcus neoformans isolates recovered from an AIDS patient
      with recurrent meningitis were analyzed. Four isolates were fluconazole
      susceptible, while the fifth isolate developed fluconazole resistance. Analysis
      of the 14-alpha lanosterol demethylase gene (ERG11) showed a point mutation in
      the resistant strain responsible for the amino acid substitution G484S.

PMID- 14576141
TI  - Antifungal combinations against Candida albicans biofilms in vitro.
AB  - Candida biofilms display increased resistance to most antifungal agents. We have
      evaluated the efficacy of combinations of fluconazole (FLC), amphotericin B, and
      caspofungin (CSP) against Candida albicans biofilms in vitro. Indifference was
      observed for all the combinations of paired antifungal agents when a checkerboard
      titration method was used. Time-kill experiments revealed an antagonistic effect
      of high FLC doses with CSP.

PMID- 14576142
TI  - Norfloxacin-induced electroencephalogram alteration and seizures in rats are not
      triggered by enhanced levels of intracerebral glutamate.
AB  - Pharmacokinetic-pharmacodynamic modeling of the electroencephalogram (EEG) effect
      was combined with intracerebral glutamate determinations using microdialysis for
      rats receiving norfloxacin intravenously (150 mg/kg of body weight). The EEG
      effect (accompanied by tremors and seizures) was consistently observed without
      glutamate level modifications. Therefore, norfloxacin-inducted seizures are not
      triggered by intracerebral glutamate level enhancement.

PMID- 14576143
TI  - Simulation of human gentamicin pharmacokinetics in an experimental Enterococcus
      faecalis endocarditis model.
AB  - Significant differences between animal and human pharmacokinetics may be
      responsible for the conflicting results of experimental studies. This study
      determined the impact of human pharmacokinetic simulation (HPS) on gentamicin
      activity in an Enterococcus faecalis endocarditis model. The decrease in
      bacterial counts was greater with HPS than with a dose-equivalent regimen without
      HPS.

PMID- 14576144
TI  - In vitro activities of a new des-fluoro(6) quinolone, garenoxacin, against
      clinical anaerobic bacteria.
AB  - The antimicrobial activities of garenoxacin and eight other antibiotics against
      641 anaerobic isolates were evaluated with the NCCLS agar dilution method.
      Overall, the MICs of garenoxacin for 50 and 90% of the strains tested (in
      micrograms per milliliter) were as follows: Bacteroides fragilis group, 0.5 and
      2; Prevotella spp., 0.25 and 2; Fusobacterium spp., 0.25 and 0.5; Porphyromonas
      spp., 0.125 and 0.25; Bilophila wadsworthia, 0.5 and 1; Veillonella spp., 0.25
      and 0.5; Clostridium spp., 0.25 and 1; Clostridium difficile, 2 and >64;
      Bifidobacterium spp., 1 and 2; Eggerthella lenta, 0.25 and 1; Propionibacterium
      spp., 0.5 and 0.5; gram-positive cocci, 0.125 and 0.25.

PMID- 14576145
TI  - Correlation between pyrazinamide activity and pncA mutations in Mycobacterium
      tuberculosis isolates in Taiwan.
AB  - A total of 76 clinical Mycobacterium tuberculosis isolates from Taiwan were
      tested for pyrazinamidase activity, pyrazinamide susceptibility, and pncA
      mutations. Frequency of resistance to PZA rose with increases in resistance to
      first-line drugs. Of 17 pyrazinamide-resistant strains, 7 (3 of which had not
      been previously described) possessed mutations in the pncA gene.

PMID- 14576146
TI  - A novel hormone-sensitive lipase isoform expressed in pancreatic beta-cells.
AB  - Hormone-sensitive lipase (HSL) is a key enzyme in fatty acid mobilization in many
      cell types. Two isoforms of HSL are known to date, namely HSL(adi) (84 kDa in
      rat) and HSL(tes) (130 kDa in rat). These are encoded by the same gene, with
      exons 1-9 encoding the parts that are common to both and an additional 5'-exon
      encoding the additional amino acids in HSL(tes). HSL of various tissues, among
      these the islet of Langerhans, is larger than HSL(adi), but not as large as
      HSL(tes), indicating that there may be other 5'-coding exons. Here we describe
      the molecular basis for a novel 89-kDa HSL isoform that is expressed in beta
      cells, adipocytes, adrenal glands, and ovaries in the rat and that is encoded by
      exons 1-9 and exon A, which is spliced to exon 1 and thereby introducing an
      upstream start codon. The additional 5'-base pairs encode a 43-amino acid
      peptide, which is highly positively charged. Conglomerates of HSL molecules are
      in close association with the secretory granules of the beta-cell, as determined
      by immunoelectron microscopy with antibodies targeting two separate regions of
      HSL. We have also determined that the human genomic sequence upstream of exon A
      has promoter activity in INS-1 cells as well as glucose sensing capability,
      mediating an increase in expression at high glucose concentration. The minimal
      promoter is present within 170 bp from the transcriptional start site and maximal
      glucose responsiveness is conferred by sequence within 850 bp from the
      transcriptional start site.

PMID- 14576148
TI  - TRPM6 forms the Mg2+ influx channel involved in intestinal and renal Mg2+
      absorption.
AB  - Mg2+ is an essential ion involved in a multitude of physiological and biochemical
      processes and a major constituent of bone tissue. Mg2+ homeostasis in mammals
      depends on the equilibrium between intestinal Mg2+ absorption and renal Mg2+
      excretion, but little is known about the molecular nature of the proteins
      involved in the transepithelial transport of Mg2+ in these organs. Recently, it
      was shown that patients with mutations in TRPM6, a member of the transient
      receptor potential family of cation channels, suffer from hypomagnesemia with
      secondary hypocalcemia (HSH) as a result of impaired renal and/or intestinal Mg2+
      handling. Here, we show that TRPM6 is specifically localized along the apical
      membrane of the renal distal convoluted tubule and the brush-border membrane of
      the small intestine, epithelia particularly associated with active Mg2+
      (re)absorption. In kidney, parvalbumin and calbindin-D28K, two divalent-binding
      proteins, are co-expressed with TRPM6 and might function as intracellular Mg2+
      buffers in the distal convoluted tubule. Heterologous expression of wild-type
      TRPM6 but not TRPM6 mutants identified in HSH patients induces a Mg2+- and Ca2+
      permeable cation channel tightly regulated by intracellular Mg2+ levels. The
      TRPM6-induced channel displays strong outward rectification, has a 5-fold higher
      affinity for Mg2+ than for Ca2+, and is blocked in a voltage-dependent manner by
      ruthenium red. Our data indicate that TRPM6 comprises all or part of the apical
      Mg2+ channel of Mg2+-absorbing epithelia.

PMID- 14576149
TI  - Functional characterization of an archaeal GroEL/GroES chaperonin system:
      significance of substrate encapsulation.
AB  - In all three kingdoms of life chaperonins assist the folding of a range of newly
      synthesized proteins. As shown recently, Archaea of the genus Methanosarcina
      contain both group I (GroEL/GroES) and group II (thermosome) chaperonins in the
      cytosol. Here we report on a detailed functional analysis of the archaeal
      GroEL/GroES system of Methanosarcina mazei (Mm) in comparison to its bacterial
      counterpart from Escherichia coli (Ec). We find that the groESgroEL operon of M.
      mazei is unable to functionally replace groESgroEL in E. coli. However, the
      MmGroES protein can largely complement a mutant EcGroES protein in vivo. The
      ATPase rate of MmGroEL is very low and the dissociation of MmGroES from MmGroEL
      is 15 times slower than for the EcGroEL/GroES system. This slow ATPase cycle
      results in a prolonged enclosure time for model substrate proteins, such as
      rhodanese, in the MmGroEL:GroES folding cage before their release into the
      medium. Interestingly, optimal functionality of MmGroEL/GroES and its ability to
      encapsulate larger proteins, such as malate dehydrogenase, requires the presence
      of ammonium sulfate in vitro. In the absence of ammonium sulfate, malate
      dehydrogenase fails to be encapsulated by GroES and rather cycles on and off the
      GroEL trans ring in a non-productive reaction. These results indicate that the
      archaeal GroEL/GroES system has preserved the basic encapsulation mechanism of
      bacterial GroEL and suggest that it has adjusted the length of its reaction cycle
      to the slower growth rates of Archaea. Additionally, the release of only the
      folded protein from the GroEL/GroES cage may prevent adverse interactions of the
      GroEL substrates with the thermosome, which is not normally located within the
      same compartment.

PMID- 14576147
TI  - Androgen control of cell proliferation and cytoskeletal reorganization in human
      fibrosarcoma cells: role of RhoB signaling.
AB  - We recently generated an HT-1080-derived cell line called HT-AR1 that responds to
      dihydrotestosterone (DHT) treatment by undergoing cell growth arrest in
      association with cytoskeletal reorganization and induction of neuroendocrine-like
      cell differentiation. In this report, we show that DHT induces a dose-dependent
      increase in G0/G1 growth-arrested cells using physiological levels of hormone.
      The arrested cells increase in cell size and contain a dramatic redistribution of
      desmoplakin, keratin 5, and chromogranin A proteins. DHT-induced cytoskeletal
      changes were also apparent from time lapse video microscopy that showed that
      androgen treatment resulted in the rapid appearance of neuronal-like membrane
      extensions. Expression profiling analysis using RNA isolated from DHT-treated HT
      AR1 cells revealed that androgen receptor activation leads to the coordinate
      expression of numerous cell signaling genes including RhoB, PTGF-beta, caveolin
      2, Egr-1, myosin 1B, and EHM2. Because RhoB has been shown to have a role in
      tumor suppression and neuronal differentiation in other cell types, we
      investigated RhoB signaling functions in the HT-AR1 steroid response. We found
      that steroid induction of RhoB was DHT-specific and that newly synthesized RhoB
      protein was post-translationally modified and localized to endocytic vesicles.
      Moreover, treatment with a farnesyl transferase inhibitor reduced DHT-dependent
      growth arrest, suggesting that prenylated RhoB might function to inhibit HT-AR1
      cell proliferation. This was directly shown by transfecting HT-AR1 cells with
      RhoB coding sequences containing activating or dominant negative mutations.

PMID- 14576150
TI  - Depletion of endogenous nitric oxide enhances cisplatin-induced apoptosis in a
      p53-dependent manner in melanoma cell lines.
AB  - The expression of inducible nitric-oxide synthase in melanoma tumor cells was
      recently shown to correlate strongly with poor patient survival after combination
      biochemotherapy (p<0.001). Furthermore, evidence suggests that nitric oxide, a
      reaction product of nitric oxide synthase, exhibits antiapoptotic activity in
      melanoma cells. We therefore hypothesized that nitric oxide antagonizes
      chemotherapy-induced apoptosis. Whether nitric oxide is capable of regulating
      cell growth and apoptotic responses to cisplatin treatment in melanoma cell lines
      was evaluated. We demonstrate herein that depletion of endogenously produced
      nitric oxide can inhibit melanoma proliferation and promote apoptosis. Moreover,
      our data indicate that the depletion of nitric oxide leads to changes in cell
      cycle regulation and enhances cisplatin-induced apoptosis in melanoma cells.
      Strikingly, we observed that the depletion of nitric oxide inhibits cisplatin
      induced wild type p53 accumulation and p21(Waf1/Cip1/Sdi1) expression in melanoma
      cells. When cisplatin-induced p53 binding to the p21(Waf1/Cip1/Sdi1) promoter was
      examined, it was found that nitric oxide depletion significantly reduced the
      presence of p53-DNA complexes after cisplatin treatment. Furthermore, dominant
      negative inhibition of p53 activity enhanced cisplatin-induced apoptosis.
      Together, these data strongly suggest that endogenously produced nitric oxide is
      required for cisplatin-induced p53 activation and p21(Waf1/Cip1/Sdi1) expression,
      which can regulate melanoma sensitivity to cisplatin.

PMID- 14576151
TI  - Characterization of the menaquinone reduction site in the diheme cytochrome b
      membrane anchor of Wolinella succinogenes NiFe-hydrogenase.
AB  - The majority of bacterial membrane-bound NiFe-hydrogenases and formate
      dehydrogenases have homologous membrane-integral cytochrome b subunits. The
      prototypic NiFe-hydrogenase of Wolinella succinogenes (HydABC complex) catalyzes
      H2 oxidation by menaquinone during anaerobic respiration and contains a membrane
      integral cytochrome b subunit (HydC) that carries the menaquinone reduction site.
      Using the crystal structure of the homologous FdnI subunit of Escherichia coli
      formate dehydrogenase-N as a model, the HydC protein was modified to examine
      residues thought to be involved in menaquinone binding. Variant HydABC complexes
      were produced in W. succinogenes, and several conserved HydC residues were
      identified that are essential for growth with H2 as electron donor and for
      quinone reduction by H2. Modification of HydC with a C-terminal Strep-tag II
      enabled one-step purification of the HydABC complex by Strep-Tactin affinity
      chromatography. The tagged HydC, separated from HydAB by isoelectric focusing,
      was shown to contain 1.9 mol of heme b/mol of HydC demonstrating that HydC
      ligates both heme b groups. The four histidine residues predicted as axial heme b
      ligands were individually replaced by alanine in Strep-tagged HydC. Replacement
      of either histidine ligand of the heme b group proximal to HydAB led to HydABC
      preparations that contained only one heme b group. This remaining heme b could be
      completely reduced by quinone supporting the view that the menaquinone reduction
      site is located near the distal heme b group. The results indicate that both heme
      b groups are involved in electron transport and that the architecture of the
      menaquinone reduction site near the cytoplasmic side of the membrane is similar
      to that proposed for E. coli FdnI.

PMID- 14576152
TI  - Identification of genetic pathways activated by the androgen receptor during the
      induction of proliferation in the ventral prostate gland.
AB  - The androgen receptor (AR), when complexed with 5alpha-dihydrotestosterone (DHT),
      supports the survival and proliferation of prostate cells, a process critical for
      normal development, benign prostatic hypertrophy, and tumorigenesis. However, the
      androgen-responsive genetic pathways that control prostate cell division and
      differentiation are largely unknown. To identify such pathways, we examined gene
      expression in the ventral prostate 6 and 24 h after DHT administration to
      androgen-depleted rats. 234 transcripts were expressed significantly differently
      from controls (p < 0.05) at both time points and were subjected to extensive data
      mining. Functional clustering of the data reveals that the majority of these
      genes can be classified as participating in induction of secretory activity,
      metabolic activation, and intracellular signaling/signal transduction, indicating
      that AR rapidly modulates the expression of genes involved in proliferation and
      differentiation in the prostate. Notably AR represses the expression of several
      key cell cycle inhibitors, while modulating members of the wnt and notch
      signaling pathways, multiple growth factors, and peptide hormone signaling
      systems, and genes involved in MAP kinase and calcium signaling. Analysis of
      these data also suggested that p53 activity is negatively regulated by AR
      activation even though p53 RNA was unchanged. Experiments in LNCaP prostate
      cancer cells reveal that AR inhibits p53 protein accumulation in the nucleus,
      providing a post-transcriptional mechanism by which androgens control prostate
      cell growth and survival. In summary these data provide a comprehensive view of
      the earliest events in AR-mediated prostate cell proliferation in vivo, and
      suggest that nuclear exclusion of p53 is a critical step in prostate growth.

PMID- 14576153
TI  - Simultaneous blockade of both the epidermal growth factor receptor and the
      insulin-like growth factor receptor signaling pathways in cancer cells with a
      fully human recombinant bispecific antibody.
AB  - Both the epidermal growth factor receptor (EGFR) and the insulin-like growth
      factor receptor (IGFR) have been implicated in the tumorigenesis of a variety of
      human cancers. Effective tumor inhibition has been achieved both experimentally
      and clinically with a number of strategies that antagonize either receptor
      activity. Here we constructed and produced two fully human recombinant bispecific
      antibodies (BsAb) that target both EGFR and IGFR, using two neutralizing human
      antibodies originally isolated from a phage display library. The BsAb not only
      retained the antigen binding capacity of each of the parent antibodies, but also
      were capable of binding to both targets simultaneously as demonstrated by a cross
      linking enzyme-linked immunosorbent assay. Furthermore, the BsAb effectively
      blocked both ligands, EGF and IGF, from binding to their respective receptors,
      and inhibited tumor cell proliferation as potently as a combination of both the
      parent antibodies. More importantly, the BsAb were able to completely block
      activation of several major signal transduction molecules, including Akt and
      p44/p42 MAP kinases, by both EGF and IGF, whereas each individual parent antibody
      was only effective in inhibiting those signal molecules activated by the relevant
      single growth factor. The BsAb molecules retained good antigen binding activity
      after incubation with mouse serum at 37 degrees C for up to 6 days. Taken
      together, our results underscore the benefits of simultaneous targeting multiple
      growth factor receptor pathways for more efficacious cancer treatment. This
      report describes the first time use of a recombinant BsAb for targeting two tumor
      associated molecules on either a single or adjacent tumor cells for enhanced
      antitumor activity.

PMID- 14576154
TI  - Non-redundant role of Shc in Erk activation by cytoskeletal reorganization.
AB  - We have shown previously that cytoskeletal reorganization (CSR) induced by
      pharmacological reagents such as colchicine or cytochalasins can up-regulate the
      urokinase-type plasminogen activator (uPA) gene via the Ras/Erk signaling
      pathway. In this present study using the small interfering RNA technique, we have
      found that ShcA adapter proteins play a rather active role in CSR-induced Erk
      activation, contrary to their mostly redundant role in other signaling pathways,
      e.g. growth factor-induced Erk activation, where Grb2 can bind directly to the
      receptor tyrosine kinase and activate Erk in the absence of ShcA. ShcA knockdown
      abolished CSR-induced activation of both Erk and the uPA promoter. Expression of
      small interfering RNA-escaping silent mutants of p52 or p46 but not p66 ShcA
      isoform efficiently rescued CSR-induced Erk activation. Moreover, we have shown
      that phosphorylation of either Tyr-239/Tyr-240 or Tyr-313 in p52(ShcA) can
      mediate CSR-induced Erk activation equally well. In a quest for molecules
      upstream of ShcA in this signaling, we found that CSR-induced ShcA tyrosine
      phosphorylation, its association with Grb2, Erk activation, and uPA gene
      expression were all dependent on Rho kinase, p38 mitogen-activated protein
      kinase, and Src. In summary, we have found a novel, non-redundant role for ShcA
      in contrast to its redundant role in many other signaling pathways.

PMID- 14576155
TI  - AKT activity determines sensitivity to mammalian target of rapamycin (mTOR)
      inhibitors by regulating cyclin D1 and c-myc expression.
AB  - Prior work demonstrates that AKT activity regulates sensitivity of cells to G(1)
      arrest induced by mammalian target of rapamycin (mTOR) inhibitors such as
      rapamycin and CCI-779. To investigate this, a novel high-throughput microarray
      polysome analysis was performed to identify genes whose mRNA translational
      efficiency was differentially affected following mTOR inhibition. The analysis
      also allowed the assessment of steady-state transcript levels. We identified two
      transcripts, cyclin D1 and c-myc, which exhibited differential expression in an
      AKT-dependent manner: High levels of activated AKT resulted in rapamycin-induced
      down-regulation of expression, whereas low levels resulted in up-regulation of
      expression. To ectopically express these proteins we exploited the finding that
      the p27(kip1) mRNA was efficiently translated in the face of mTOR inhibition
      irrespective of AKT activity. Thus, the p27(kip1) 5'-untranslated region was
      fused to the cyclin D1 and c-myc coding regions and these constructs were
      expressed in cells. In transfected cells, expression of cyclin D1 or c-myc was
      not decreased by rapamycin. Most importantly, this completely converted sensitive
      cells to a phenotype resistant to G(1) arrest. Furthermore, the AKT-dependent
      differential expression patterns of these two genes was also observed in a mouse
      xenograft model following in vivo treatment with CCI-779. These results identify
      two critical downstream molecular targets whose expression is regulated by AKT
      activity and whose down-regulation is required for rapamycin/CCI-779 sensitivity.

PMID- 14576157
TI  - Binding of the replication terminator protein Fob1p to the Ter sites of yeast
      causes polar fork arrest.
AB  - Fob1p protein has been implicated in the termination of replication forks at the
      two tandem termini present in the non-transcribed spacer region located between
      the sequences encoding the 35 S and the 5 S RNAs of Saccharomyces cerevisiae.
      However, the biochemistry and mode of action of this protein were previously
      unknown. We have purified the Fob1p protein to near-homogeneity, and we developed
      a novel technique to show that it binds specifically to the Ter1 and Ter2
      sequences. Interestingly, the two sequences share no detectable homology. We
      present two lines of evidence showing that the interaction of the Fob1p with the
      Ter sites causes replication termination. First, a mutant of FOB1, L104S, that
      significantly reduced the binding of the mutant form of the protein to the tandem
      Ter sites, also failed to promote replication termination in vivo. The mutant did
      not diminish nucleolar transport, and interaction of the mutant form of Fob1p
      with itself and with another protein encoded in the locus YDR026C suggested that
      the mutation did not cause global misfolding of the protein. Second, DNA site
      mutations in the Ter sequences that separately and specifically abolished
      replication fork arrest at Ter1 or Ter2 also eliminated sequence-specific binding
      of the Fob1p to the two sites. The work presented here definitively established
      Ter DNA-Fob1p interaction as an important step in fork arrest.

PMID- 14576156
TI  - Molecular basis for atovaquone resistance in Pneumocystis jirovecii modeled in
      the cytochrome bc(1) complex of Saccharomyces cerevisiae.
AB  - Atovaquone is a substituted hydroxynaphthoquinone that is widely used to prevent
      and clear Plasmodium falciparum malaria and Pneumocystis jirovecii pneumonia.
      Atovaquone inhibits respiration in target organisms by specifically binding to
      the ubiquinol oxidation site at center P of the cytochrome bc(1) complex. The
      failure of atovaquone treatment and mortality of patients with malaria and P.
      jirovecii pneumonia has been linked to the appearance of mutations in the
      cytochrome b gene. To better understand the molecular basis of atovaquone
      resistance, we have introduced seven of the mutations from atovaquone-resistant
      P. jirovecii into the cytochrome b gene of Saccharomyces cerevisiae and thus
      obtained cytochrome bc(1) complexes resistant to inhibition by atovaquone. In
      these enzymes, the IC(50) for atovaquone increases from 25 nm for the enzyme from
      wild-type yeast to >500 nm for some of the mutated enzymes. Modeling of the
      changes in cytochrome b structure and atovaquone binding with the mutated bc(1)
      complexes provides the first quantitative explanation for the molecular basis of
      atovaquone resistance.

PMID- 14576158
TI  - Extramembrane central pore of multidrug exporter AcrB in Escherichia coli plays
      an important role in drug transport.
AB  - We previously reported the crystal structure of the major multidrug exporter AcrB
      in Escherichia coli (Murakami, S., Nakashima, R., Yamashita, E., and Yamaguchi,
      A. (2002) Nature 419, 587-593). The extramembrane headpiece of the AcrB trimer
      contains a central pore composed of three alpha-helices. Each pore helix belongs
      to a different monomer. In this study, we constructed cysteine-scanning mutants
      as to the residues comprising the pore helix. Of the 21 mutants (D99C to P119C),
      5 (D101C, V105C, N109C, Q112C, and P116C) showed significantly reduced drug
      resistance and drug-exporting activity. These residues are localized on one side
      of the pore helix, i.e. on the wall of the pore. These observations strongly
      indicate the important role of this pore in the drug transport process. A N
      ethylmaleimide binding experiment revealed that the pore is in the closed state,
      and the thickness of the permeability barrier in the middle of the pore
      corresponds to 2.5 alpha-helical turns. Two mutants (V105C and Q112C), which
      showed the greatest loss of activity of all of the pore mutants, were detected in
      the form of disulfide cross-linking dimers under normal conditions, suggesting
      that a conformational change of the pore is indispensable during the transport
      process.

PMID- 14576159
TI  - The cellular prion protein PrPc is expressed in human enterocytes in cell-cell
      junctional domains.
AB  - The physiological function of PrPc, the cellular isoform of prion protein, still
      remains unclear, although it has been established, in vitro or by using nerve
      cells, that it can homodimerize, bind copper, or interact with other proteins.
      Expression of PrPc was demonstrated as necessary for prion infection propagation.
      Considering the importance of the intestinal barrier in the process of oral prion
      infectivity, we have analyzed the expression of PrPc in enterocytes, which
      represent the major cell population of the intestinal epithelium. Our study,
      conducted both on normal human intestinal tissues and on the enterocytic cell
      line Caco-2/TC7, shows for the first time that PrPc is present in enterocytes.
      Interestingly, we found that this glycosylphosphatidylinositol-anchored
      glycoprotein was localized in cholesterol-dependent raft domains of the upper
      lateral membranes of enterocytes, beneath tight junctions, in cell-cell
      junctional domains. We observed that PrPc, E-cadherin, and Src co-localized in
      adherens junctions and that PrPc was co-immunoprecipitated with Src kinase but
      not with E-cadherin. Alteration of cell polarity after cholesterol depletion or
      loosening of the cell-cell junctions after EGTA treatment rapidly impaired
      membrane targeting of PrPc. Overall, our results point out the signaling of cell
      cell contacts as a putative role for PrPc in epithelial cells.

PMID- 14576160
TI  - Inactivation of the chloroplast ATP synthase gamma subunit results in high non
      photochemical fluorescence quenching and altered nuclear gene expression in
      Arabidopsis thaliana.
AB  - The nuclear atpC1 gene encoding the gamma subunit of the plastid ATP synthase has
      been inactivated by T-DNA insertion mutagenesis in Arabidopsis thaliana. In the
      seedling-lethal dpa1 (deficiency of plastid ATP synthase 1) mutant, the absence
      of detectable amounts of the gamma subunit destabilizes the entire ATP synthase
      complex. The expression of a second gene copy, atpC2, is unaltered in dpa1 and is
      not sufficient to compensate for the lack of atpC1 expression. However, in vivo
      protein labeling analysis suggests that assembly of the ATP synthase alpha and
      beta subunits into the thylakoid membrane still occurs in dpa1. As a consequence
      of the destabilized ATP synthase complex, photophosphorylation is abolished even
      under reducing conditions. Further effects of the mutation include an increased
      light sensitivity of the plant and an altered photosystem II activity. At low
      light intensity, chlorophyll fluorescence induction kinetics is close to those
      found in wild type, but non-photochemical quenching strongly increases with
      increasing actinic light intensity resulting in steady state fluorescence levels
      of about 60% of the minimal dark fluorescence. Most fluorescence quenching
      relaxed within 3 min after dark incubation. Spectroscopic and biochemical studies
      have shown that a high proton gradient is responsible for most quenching.
      Thylakoids of illuminated dpa1 plants were swollen due to an increased proton
      accumulation in the lumen. Expression profiling of 3292 nuclear genes encoding
      mainly chloroplast proteins demonstrates that most organelle functions are down
      regulated. On the contrary, the mRNA expression of some photosynthesis genes is
      significantly up-regulated, probably to compensate for the defect in dpa1.

PMID- 14576161
TI  - The peptides acetyl-(Gly-3(S)Hyp-4(R)Hyp)10-NH2 and acetyl-(Gly-Pro-3(S)Hyp)10
      NH2 do not form a collagen triple helix.
AB  - Hydroxylation of proline residues in the Yaa position of the Gly-Xaa-Yaa repeated
      sequence to 4(R)-hydroxyproline is essential for the formation of the collagen
      triple helix. A small number of 3(S)-hydroxyproline residues are present in most
      collagens in the Xaa position. Neither the structural nor a biological role is
      known for 3(S)-hydroxyproline. To characterize the structural role of 3(S)
      hydroxyproline, the peptide Ac-(Gly-3(S)Hyp-4(R)Hyp)10-NH2 was synthesized and
      analyzed by circular dichroism spectroscopy, analytical ultracentrifugation, and
      1H nuclear magnetic resonance spectroscopy. At 4 degrees C in water the circular
      dichroism spectrum indicates that this peptide was in a polyproline-II-like
      secondary structure with a positive peak at 225 nm similar to Ac-(Gly-Pro
      4(R)Hyp)10-NH2. The positive peak at 225 nm almost linearly decreases with
      increasing temperature to 95 degrees C without an obvious transition. Although
      the peptide Ac-(Gly-Pro-4(R)Hyp)10-NH2 forms a trimer at 10 degrees C,
      sedimentation equilibrium experiments indicate that Ac-(Gly-3(S)Hyp-4(R)Hyp)10
      NH2 is a monomer in water at 7 degrees C. To study the role of 3(S)
      hydroxyproline in the Yaa position, we synthesized Ac-(Gly-Pro-3(S)Hyp)10-NH2.
      This peptide also does not form a triple helix in water. 1H Nuclear magnetic
      resonance spectroscopy data (including line widths and nuclear Overhauser
      effects) are entirely consistent, with neither Ac-(Gly-3(S)Hyp-4(R)Hyp)10-NH2 nor
      Ac-(Gly-Pro-3(S)Hyp)10-NH2 forming a triple helix in water. Therefore 3(S)
      hydroxyproline destabilizes the collagen triple helix in either position. In
      contrast, when 3(S)-hydroxyproline is inserted as a guest in the highly stable 
      Gly-Pro-4(R)Hyperepeated host sequence, Ac-(Gly-Pro-4(R)Hyp)3-Gly-3(S)Hyp-4(R)Hyp
      (Gly-Pro-4(R)Hyp)4-Gly-Gly-NH2 forms as stable a trimer (Tm=49.6 degrees C) as Ac
      (Gly-Pro-4(R)Hyp)8-Gly-Gly-NH2 (Tm=48.9 degrees C). Given that Ac-(Gly-Pro
      4(R)Hyp)3-Gly-4(R)Hyp-Pro-(Gly-Pro-4(R)Hyp)4-Gly-Gly-NH2 forms a triple helix
      nearly as stable as the above two peptides (Tm=45.0 degrees C) and the knowledge
      that Ac-(Gly-4(R)Hyp-Pro)10-NH2 does not form a triple helix, we conclude that
      the host environment dominates the structure of host-guest peptides and that
      these peptides are not necessarily accurate predictors of triple helical
      stability.

PMID- 14576162
TI  - Metallothionein protects islets from hypoxia and extends islet graft survival by
      scavenging most kinds of reactive oxygen species.
AB  - Islet transplantation is a promising therapy for Type 1 diabetes, but many
      attempts have failed due to early graft hypoxia or immune rejection, which
      generate reactive oxygen species (ROS). In the current study, we determined that
      transgenic overexpression of the antioxidant metallothionein (MT) in pancreatic
      beta cells provided broad resistance to oxidative stress by scavenging most kinds
      of ROS including H2O2, peroxynitrite radical released from streptozotocin, 3
      morpholinosydnonimine (SIN-1), and superoxide radical produced by
      xanthine/xanthine oxidase. MT also reduced nitric oxide-induced beta cell death.
      A direct test of hypoxia/reperfusion sensitivity was made by exposing FVB and MT
      islets to hypoxia (1% O2). MT markedly reduced ROS production and improved islet
      cell survival. Because MT protected beta cells from a broad spectrum of ROS and
      from hypoxia, we considered it to be an ideal candidate for improving islet
      transplantation. We first tested syngeneic transplantation by implanting islets
      under the kidney capsule of the same strain, FVB mice, thereby eliminating the
      immune rejection component. Under these conditions, MT islets maintained much
      greater insulin content than control islets. Allotransplantation was then tested.
      MT transgenic and normal FVB islets were implanted under the kidney capsule of
      BALB/c mice that were previously treated with streptozotocin to induce diabetes.
      We found that MT islets extended the duration of euglycemia 2-fold longer than
      nontransgenic islets. The benefit of MT was due to protection from ROS since
      nitrotyrosine staining, an indicator of free radical damage, was much lower in MT
      grafts than in FVB grafts. The time course of protection suggested that the major
      mode of MT action may have been protection from hypoxia or hypoxia/reperfusion.
      These data demonstrate that treatment with a broad spectrum antioxidant protects
      islets from ROS damage such as that produced during the early phase of islet
      transplantation.

PMID- 14576163
TI  - Insulin-like growth factor-independent effects mediated by a C-terminal metal
      binding domain of insulin-like growth factor binding protein-3.
AB  - Insulin-like growth factors (IGFs) play a central role in the integration of
      proliferative and survival responses of most mammalian cell types. IGF-binding
      protein-3 (IGFBP-3) influences IGF action directly as a carrier of IGFs but also
      modulates these actions indirectly via independent mechanisms involving
      interactions with plasma, extracellular matrix and cell surface molecules,
      conditional proteolysis, cellular uptake, and nuclear transport. Here we
      demonstrate that a short C-terminal metal-binding domain (MBD) of IGFBP-3
      mediates binding to metals. MBD epitopes, sequestered in the intact molecule, are
      unmasked by incubation in the presence of ferrous (but not ferric or zinc) ions.
      An isolated 14-mer MBD peptide triggered apoptotic effects in stressed HEK293
      cells as effectively as IGFBP-3. The MBD, which encompasses a nuclear
      localization sequence and an adjacent putative caveolin-binding sequence,
      mobilizes rapid cellular uptake and nuclear localization of unrelated proteins
      such as green fluorescent protein and streptavidin-horseradish peroxidase
      conjugate. Metal ions stimulate MBD-mediated cellular/nuclear uptake in vivo.
      Cross-linking studies showed a direct physical interaction of MBD with integrins
      alphav and beta1, caveolin-1, and transferrin receptor. MBD-mediated protein
      mobilization and pro-apoptotic effects are inhibited by nystatin but not
      chlorpromazine, suggesting an involvement of caveolar-mediated endocytosis.
      However, MBD effects are inhibited by antibodies to transferrin receptor or
      integrins. These results are discussed with particular reference to the cell
      target specificity of IGFBP-3 in disease processes such as cancer and
      atherosclerosis.

PMID- 14576164
TI  - Cellular internalization of insulin-like growth factor binding protein-3:
      distinct endocytic pathways facilitate re-uptake and nuclear localization.
AB  - Insulin-like growth factor binding protein-3 (IGFBP-3) is well established as a
      growth-inhibitory, apoptosis-inducing secreted molecule that acts via insulin
      like growth factor (IGF)-independent as well as IGF-dependent pathways. Nuclear
      localization of IGFBP-3 has been observed and nuclear binding partners for IGFBP
      3 demonstrated. However, little is known about the mechanism of IGFBP-3
      internalization. We hypothesized that IGFBP-3 is first secreted then taken up
      again into cells and that its internalization could occur via binding to
      transferrin or caveolin. Incubation of cells with an IGFBP-3-neutralizing
      antibody demonstrated that nuclear translocation of endogenous IGFBP-3 requires
      IGFBP-3 secretion and re-uptake. Nuclear localization of exogenously added IGFBP
      3 was rapid, occurring within 15 min, inhibited by co-incubation and
      extracellular sequestration with IGF-I, and dependent on the transferrin-binding
      C-terminal peptide region of IGFBP-3. Co-immunoprecipitation assays confirmed
      that IGFBP-3 binds transferrin but not directly to the transferrin receptor
      (TfR1); however, transferrin binds TfR1 and a ternary complex is formed. Specific
      binding to caveolin scaffolding docking sequence was confirmed utilizing
      radiolabeled IGFBP-3. Blocking TfR1-mediated endocytosis prevents both endogenous
      and exogenous IGFBP-3 re-uptake and inhibitors of caveolae formation also retard
      IGFBP-3 nuclear entry. Co-treatment with anti-transferrin receptor antibody and
      cholesterol depletion agents completely abolished endogenous and exogenous IGFBP
      3 uptake. Suppression of IGFBP-3 internalization by TfR1 blockade inhibited IGFBP
      3-induced apoptosis. Together, these data indicate that the actions of IGFBP-3
      are mediated by internalization via distinct endocytic pathways.

PMID- 14576165
TI  - Phosphorylation of presenilin 1 at the caspase recognition site regulates its
      proteolytic processing and the progression of apoptosis.
AB  - The Alzheimer's disease-associated presenilin (PS) 1 is intimately involved in
      gamma-secretase cleavage of beta-amyloid precursor protein and other proteins. In
      addition, PS1 plays a role in beta-catenin signaling and in the regulation of
      apoptosis. Here we demonstrate that phosphorylation of PS1 is regulated by two
      independent signaling pathways involving protein kinase (PK) A and PKC and that
      both kinases can directly phosphorylate the large hydrophilic domain of PS1 in
      vitro and in cultured cells. A phosphorylation site at serine residue 346 was
      identified that is selectively phosphorylated by PKC but not by PKA. This site is
      localized within a recognition motif for caspases, and phosphorylation strongly
      inhibits proteolytic processing of PS1 by caspase activity during apoptosis.
      Moreover, PS1 phosphorylation reduces the progression of apoptosis. Our data
      indicate that phosphorylation/dephosphorylation at the caspase recognition site
      provides a mechanism to reversibly regulate properties of PS1 in apoptosis.

PMID- 14576166
TI  - Activation of the pro-survival phosphatidylinositol 3-kinase/AKT pathway by
      transforming growth factor-beta1 in mesenchymal cells is mediated by p38 MAPK
      dependent induction of an autocrine growth factor.
AB  - Transforming growth factor-beta1 (TGF-beta1) is a multifunctional cytokine
      involved in differentiation, growth, and survival of mesenchymal cells while
      inhibiting growth/survival of most other cell types. The mechanism(s) of pro
      survival signaling by TGF-beta1 in mesenchymal cells is unclear. In this report,
      we demonstrate that TGF-beta1 protects against serum deprivation-induced
      apoptosis of mesenchymal cells isolated from patients with acute lung injury and
      of normal human fetal lung fibroblasts (IMR-90). TGF-beta receptor(s)-activated
      signaling in these cells involves rapid activation of the Smad and p38 MAPK
      pathways within minutes of TGF-beta1 treatment followed by a more delayed
      activation of the pro-survival phosphatidylinositol 3-kinase-protein kinase B
      (PKB)/Akt pathway. Pharmacological inhibition of p38 MAPK with SB203580 or
      expression of a p38 kinase-deficient mutant protein inhibits TGF-beta1-induced
      PKB/Akt phosphorylation. Conditioned medium from TGF-beta1-treated cells rapidly
      induces PKB/Akt activation in an SB203580- and suramin-sensitive manner,
      suggesting p38 MAPK-dependent production of a secreted growth factor that
      activates this pro-survival pathway by an autocrine/paracrine mechanism.
      Inhibition of the phosphatidylinositol 3-kinase-PKB/Akt pathway blocks TGF-beta1
      induced resistance to apoptosis. These results demonstrate the activation of a
      novel TGF-beta1-activated pro-survival/anti-apoptotic signaling pathway in
      mesenchymal cells/fibroblasts that may explain cell-specific actions of TGF-beta1
      and provide mechanistic insights into its pro-fibrotic and tumor-promoting
      effects.

PMID- 14576167
TI  - Bone morphogenetic protein receptor IB signaling mediates apoptosis independently
      of differentiation in osteoblastic cells.
AB  - Bone morphogenetic protein-2 (BMP-2) is an important regulator of osteoblast
      differentiation. However, the regulation of osteoblast apoptosis by BMP signaling
      remains poorly understood. Here we examined the role of type I BMP receptor (BMP
      RI) in osteoblast apoptosis promoted by BMP-2. Despite undetectable BMP-RIB
      expression in OHS4 cells, BMP-2 or BMP-2 overexpression increased osteoblast
      differentiation similarly as in SaOS2 cells which express BMP-RIB, as shown by
      alkaline phosphatase and CBFA1/RUNX2 expression. In contrast to SaOS2 cells,
      however, BMP-2 or BMP-2 overexpression did not increase caspase-9 and caspases-3,
      -6, and -7 activity and DNA fragmentation in OHS4 cells. Consistently, BMP-2
      increased protein kinase C (PKC) activity, and PKC inhibition suppressed BMP-2
      induced caspase activity in SaOS2 but not in OHS4 cells that lack BMP-RIB. A
      dominant negative BMP-RIB inhibited BMP-2-induced caspase activity, whereas wild
      type BMP-RIB promoted caspase activity induced by BMP-2 in SaOS2 and MC3T3-E1
      cells. Wild-type BMP-RIB rescued the apoptotic response to BMP-2, and a
      constitutively active BMP-RIB restored the apoptotic signal in OHS4 cells,
      supporting an essential role for BMP-RIB in osteoblast apoptosis. We also
      assessed whether BMP-2-induced apoptosis occurred independently of osteoblast
      differentiation. General inhibition of caspases did not abolish BMP-2-induced
      alkaline phosphatase and CBFA1/RUNX2 expression in SaOS2 cells. Furthermore,
      broad caspases inhibition increased matrix mineralization but did not reverse the
      BMP-2 effect on mineralization in MC3T3-E1 cells. These results indicate that BMP
      2-induced apoptosis was mediated by BMP-RIB in osteoblasts and occurred
      independently of BMP-2-induced osteoblast differentiation, which provides
      additional insights into the dual mechanism of BMP-2 action on osteoblast fate.

PMID- 14576169
TI  - Carbohydrate recognition by enterohemorrhagic Escherichia coli: characterization
      of a novel glycosphingolipid from cat small intestine.
AB  - A key virulence trait of pathogenic bacteria is the ability to bind to receptors
      on mucosal cells. Here the potential glycosphingolipid receptors of
      enterohemorrhagic Escherichia coli were examined by binding of 35S-labeled
      bacteria to glycosphingolipids on thin-layer chromatograms. Thereby a selective
      interaction with two nonacid glycosphingolipids of cat small intestinal
      epithelium was found. The binding-active glycosphingolipids were isolated and, on
      the basis of mass spectrometry, proton NMR spectroscopy, and degradation studies,
      identified as Galalpha3Galbeta4Glcbeta1Cer (isoglobotriaosylceramide) and
      Galalpha3Galalpha3Galbeta4Glcbeta1Cer. The latter glycosphingolipid has not been
      described before. The interaction was not based on terminal Galalpha3 because the
      bacteria did not recognize the structurally related glycosphingolipids
      Galalpha3Galalpha4Galbeta4Glcbeta1Cer and
      Galalpha3Galbeta4GlcNAcbeta3Galbeta4Glcbeta1Cer (B5 glycosphingolipid). However,
      further binding assays using reference glycosphingolipids showed that the
      enterohemorrhagic E. coli also bound to lactosylceramide with phytosphingosine
      and/or hydroxy fatty acids, suggesting that the minimal structural element
      recognized is a correctly presented lactosyl unit. Further binding of
      neolactotetraosylceramide, lactotetraosylceramide, the Le(a)-5 glycosphingolipid,
      as well as a weak binding to gangliotriaosylceramide and
      gangliotetraosylceramide, was found in analogy with binding patterns that
      previously have been described for other bacteria classified as lactosylceramide
      binding.

PMID- 14576168
TI  - A mammalian homolog of Drosophila melanogaster transcriptional coactivator
      intersex is a subunit of the mammalian Mediator complex.
AB  - The multiprotein Mediator complex is a coactivator required for transcriptional
      activation of RNA polymerase II transcribed genes by DNA binding transcription
      factors. We previously partially purified a Med8-containing Mediator complex from
      rat liver nuclei (Brower, C. S., Sato, S., Tomomori-Sato, C., Kamura, T., Pause,
      A., Stearman, R., Klausner, R. D., Malik, S., Lane, W. S., Sorokina, I., Roeder,
      R. G., Conaway, J. W., and Conaway, R. C. (2002) Proc. Natl. Acad. Sci. U. S. A.
      99, 10353-10358). Analysis of proteins present in the most highly enriched
      Mediator fractions by tandem mass spectrometry led to the identification of
      several new mammalian Mediator subunits, as well as several potential Mediator
      subunits. Here we identify one of these proteins, encoded by the previously
      uncharacterized AK000411 open reading frame, as a new subunit of the mammalian
      Mediator complex. The AK000411 protein, which we designate hIntersex (human
      Intersex), shares significant sequence similarity with the Drosophila
      melanogaster intersex protein, which has functional properties expected of a
      transcriptional coactivator specific for the Drosophila doublesex transactivator.
      In addition, we show that hIntersex assembles into a subcomplex with Mediator
      subunits p28b and TRFP. Taken together, our findings identify a new subunit of
      the mammalian Mediator and shed new light on the architecture of the mammalian
      Mediator complex.

PMID- 14576170
TI  - Beta1,4-N-Acetylglucosaminyltransferase III down-regulates neurite outgrowth
      induced by costimulation of epidermal growth factor and integrins through the
      Ras/ERK signaling pathway in PC12 cells.
AB  - A rat pheochromocytoma cell line (PC12), when transfected with beta1,4-N
      acetylglucosaminyltransferase III (GnT-III), which catalyzes the formation of a
      bisecting GlcNAc structure in N-glycans, resulted in the suppression of neurite
      outgrowth induced by costimulation of epidermal growth factor (EGF) and
      integrins. The neurite outgrowth was restored by the overexpression of a
      constitutively activated mitogen- or extracellular signal-regulated kinase kinase
      1 (MEK-1). Consistent with this, the EGF receptor (EGFR)-mediated ERK activation
      was blocked in GnT-III transfectants. Conversely, the overexpression of dominant
      negative MEK-1 or treatment with PD98059, a specific inhibitor of MEK-1,
      inhibited neurite outgrowth in controls transfected with mock. Furthermore GnT
      III activity is required for these inhibitions, because the overexpression of a
      dominant negative GnT-III mutant (D321A) failed to reduce neurite outgrowth and
      EGFR-mediated ERK activation. Lectin blot analysis confirmed that EGFR from wild
      type GnT-III transfectants had been modified by bisecting GlcNAc in its N-glycan
      structures. This modification led to a significant decrease in EGF binding and
      EGFR autophosphorylation. Collectively, the results constitute a comprehensive
      body of evidence to show clearly that the overexpression of GnT-III prevents
      neurite outgrowth induced by costimulation of EGF and integrins through the
      Ras/MAPK activation pathway and indicates that GnT-III may be an important
      regulator for cell differentiation in neural tissues.

PMID- 14576171
TI  - Hydrolysis, lactonization, and identification of alpha(2 --> 8)/alpha(2 --> 9)
      alternatively linked tri-, tetra-, and polysialic acids.
AB  - Alpha-(2 --> 8)/alpha(2 --> 9) alternatively linked polysialic acid (PSA) can be
      identified by controlled hydrolysis followed by the analysis with capillary
      electrophoresis (CE). Due to the different stability of alpha(2 --> 8) and
      alpha(2 --> 9) linkages in acidic hydrolysis, oligosialic acids (OSAs) from the
      hydrolysis of alpha(2 --> 8)/alpha(2 --> 9) OSA/PSA could be classified into two
      groups in the CE profile. The group with an odd numerical degree of
      polymerization (DP) had two peaks in the CE profile, and the other group, with
      even number of DP, showed one peak. Each alternating alpha(2 --> 8)/alpha(2 -->
      9) linked OSA contains two isomers: one starts with the alpha(2 --> 8) linkage
      from the nonreducing end and the other starts with the alpha(2 --> 9) linkage
      from the nonreducing end. Trimers and tetramers were isolated by using a Mono Q
      column with an HPLC system. The two trimer isomers are alpha(2 --> 8)/alpha(2 -->
      9) and alpha(2 --> 9)/alpha(2 --> 8) linkages and only showed partial separation
      by CE. After lactonization, sialidase hydrolysis, and alkaline treatment, the two
      trimer isomers could be separated and identified by CE analysis, but only the
      alpha(2 --> 8)/alpha(2 --> 9) trimer could be converted to the dilactone in
      glacial acetic acid. The two tetramer isomers could be converted to four
      monolactones and three dilactones. These lactonized species could be identified
      on the basis of several principles in sialidase hydrolysis and lactonization. In
      conclusion, regioselectivity on the lactonization of oligosialic acids proceeds
      under several principles: (1) Lactonization takes place more easily in the
      alpha(2 --> 8) linkage than in the alpha(2 --> 9) linkage; (2) all of the
      positions of alpha(2 --> 8) linkages in alpha(2 --> 8)/alpha(2 --> 9)
      alternatively linked OSA can be lactonized regardless of external or internal
      carboxyl groups involved; and (3) for the site of alpha(2 --> 9) linkage, only
      internal carboxyl groups can be lactonized.

PMID- 14576172
TI  - Human galectin-1 recognition of poly-N-acetyllactosamine and chimeric
      polysaccharides.
AB  - Human galectin-1 is a dimeric carbohydrate binding protein (Gal-1) (subunit 14.6
      kDa) widely expressed by many cells but whose carbohydrate binding specificity is
      not well understood. Because of conflicting evidence regarding the ability of
      human Gal-1 to recognize N-acetyllactosamine (LN, Galbeta4GlcNAc) and poly-N
      acetyllactosamine sequences (PL, [-3Galbeta4GlcNAcbeta1-]n), we synthesized a
      number of neoglycoproteins containing galactose, N-acetylgalactosamine, fucose,
      LN, PL, and chimeric polysaccharides conjugated to bovine serum albumin (BSA).
      All neoglycoproteins were characterized by MALDI-TOF. Binding was determined in
      ELISA-type assays with immobilized neoglycoproteins and apparent binding
      affinities were estimated. For comparison, we also tested the binding of these
      neoglycoconjugates to Ricinus communis agglutinin I, (RCA-I, a galactose-binding
      lectin) and Lycopersicon esculentum agglutinin (LEA, or tomato lectin), a PL
      binding lectin. Gal-1 bound to immobilized Galbeta4GlcNAcbeta3Galbeta4Glc-BSA
      with an apparent K(d) of approximately 23 micro M but bound better to BSA
      conjugates with long PL and chimeric polysaccharide sequences (K(d)'s ranging
      from 11.9 +/- 2.9 microM to 20.9 +/- 5.1 micro M). By contrast, Gal-1 did not
      bind glycans lacking a terminal, nonreducing unmodified LN disaccharide and also
      bound very poorly to lactosyl-BSA (Galbeta4Glc-BSA). By contrast, RCA bound well
      to all glycans containing terminal, nonreducing Galbeta1-R, including lactosyl
      BSA, and bound independently of the modification of the terminal, nonreducing LN
      or the presence of PL. LEA bound with increasing affinity to unmodified PL in
      proportion to chain length. Thus Gal-1 binds terminal beta4Gal residues, and its
      binding affinity is enhanced significantly by the presence of this determinant on
      long-chain PL or chimeric polysaccharides.

PMID- 14576173
TI  - LacZ expression in Fut2-LacZ reporter mice reveals estrogen-regulated
      endocervical glandular expression during estrous cycle, hormone replacement, and
      pregnancy.
AB  - The secretor gene (FUT2) encodes an alpha(1,2)fucosyltransferase (E.C. 2.4.1.69)
      that elaborates alpha(1,2)fucose residues on mucosal epithelium and secreted
      mucins. Though uterine alpha(1,2)fucosylated glycans have been proposed to be
      involved in embryo adhesion, mice with a homozygous null mutation of Fut2
      displayed normal fertility. To help develop alternative hypotheses for function,
      the cell type and regulation of Fut2 expression during the estrous cycle, hormone
      replacement, and pregnancy was examined in Fut2-LacZ reporter mice containing
      targeted replacement of Fut2 with bacterial lacZ. LacZ expression in the
      reproductive tract of Fut2-LacZ mice is most prominent in the glandular
      epithelium of the endocervix during estrus and pregnancy. Nuclear LacZ expression
      identifies cell-specific expression of Fut2 in mucus-secreting cells of the
      endocervix, uterine glands, foveolar pit and chief cells of the stomach, and
      goblet cells of the colon. In ovariectomized Fut2-LacZ mice, estradiol treatment
      stimulates X-gal staining in endocervix and uterus but does not affect expression
      in stomach and colon. Northern blot analysis in wild-type mice shows 15-fold
      elevations of Fut2 steady-state mRNA with estradiol treatment, whereas Fut1
      varies little. Fut2 levels in the glandular stomach and distal colon remain
      constant, and uterine Fut2 levels vary eightfold during the estrous cycle. These
      data represent the first demonstration of a glycosyltransferase gene under tissue
      specific hormonal regulation in a LacZ reporter mouse model. Endocervical
      expression of Fut2 in estrus and pregnancy may modify cervical mucus barrier
      properties from microbial infection analogous to the potential role of mucosal
      glycans in humans.

PMID- 14576174
TI  - Upon thyrotropin binding the thyrotropin receptor is internalized and localized
      to endosome.
AB  - To study the fate of TSH receptor (TSHR) on TSH binding, we constructed a
      chimeric cDNA that encodes a yellow fluorescent protein (YFP) fused to the
      carboxyl terminus of human TSHR. The protein expression in transfected cells was
      confirmed using flow cytometry. The functionality of the chimeric protein was
      determined by its ability to transduce signal leading to activation of cAMP in a
      TSH dose-dependent manner. The levels of cAMP produced by these cells were
      comparable with the levels seen in cells transfected with unfused TSHR without
      the YFP. Using deconvolution microscopy, we observed that the receptor is largely
      expressed on the cell surface, but on addition of TSH, some of the receptors were
      rapidly internalized. This conclusion was supported by several independent
      observations involving different cells expressing either native or recombinant
      TSHR. On TSH treatment, we observed internalization of human TSHR-YFP and human
      TSHR, expressed on 293 and CHO cells, respectively. This was further
      substantiated when we observed colocalization of rhodamine-labeled TSH with TSHR
      YFP within the cell and by the uptake of radiolabeled TSH. Furthermore, shortly
      after ligand binding, there was a profound change in the morphology of the cells
      and some of the receptors accumulated in the perinuclear region of the cell. The
      TSHR-YFP was colocalized with RhoB-cyan fluorescent protein, indicating that it
      accumulated within the endosomes. These results indicate that the receptor
      internalization might in part be responsible for TSHR desensitization on TSH
      binding.

PMID- 14576175
TI  - High dietary fructose induces a hepatic stress response resulting in cholesterol
      and lipid dysregulation.
AB  - High-fructose feeding causes diet-induced alterations of lipid metabolism and
      decreased insulin sensitivity with alterations of hepatic pyruvate dehydrogenase
      and hepatic very low-density lipoprotein secretion. Inflammatory cytokines also
      induce dramatic changes in lipid metabolism, particularly in serum triglycerides
      via increased hepatic secretion and/or delayed clearance of very low-density
      lipoprotein. The aim of this study was to determine whether the mechanism of
      lipid dysregulation in the high-fructose diet is induced by stress response
      pathways. Animals were fed a high-fructose diet for 14 d to establish
      hypertriglyceridemia and then were treated with lipoxygenase inhibitors for 4 d
      concurrent with the diet. At the end of drug treatment, the animals were divided
      into two groups and treated with lipopolysaccharide or a vehicle. Serum samples
      were taken pretreatment and posttreatment, and liver tissue was harvested at the
      end of study. Serum samples were tested for metabolic parameters, and the tissue
      samples were tested for metabolic and stress pathway responses. Our results show
      that fructose-fed rats have changes in the c-Jun N-terminal kinase pathway with
      correspondingly elevated activator protein-1 activity, consistent with an
      inflammatory response. Treatment with lipoxygenase inhibitors reversed the
      hypertriglyceridemia and also reduced activator protein-1 activation, suggesting
      that the basis for lipid dysregulation in this model is due to activation of
      inflammatory pathways in the liver.

PMID- 14576176
TI  - The evolutionarily conserved gonadotropin-releasing hormone II modifies food
      intake.
AB  - GnRH is an evolutionarily conserved peptide of which there are multiple
      structural variants. One form, GnRH II, is the most widespread in vertebrates,
      but its primary function remains unclear. In female musk shrews, administration
      of GnRH II, but not GnRH I, reinstates mating behavior previously inhibited by
      food restriction. Because this finding suggests that the function of GnRH II may
      be linked to energetic status, we tested whether GnRH II directly affects food
      intake. Adult female musk shrews were maintained on ad libitum feeding or food
      restricted for 48 h, after which they were infused centrally with GnRH I (1
      microg), GnRH II (1 microg), or saline. Food intake was recorded 90 min, and 3,
      6, 24, and 48 h after infusion. GnRH II administration, but not saline or GnRH I,
      reduced 24-h food intake in ad libitum animals. Short-term food intake (90 min
      and 3 h) of both ad libitum and underfed shrews receiving GnRH II was also
      reduced by as much as 33%, relative to the food intake of saline-infused
      controls. GnRH I infusion did not affect short-term food intake differently than
      saline infusion in shrews fed ad libitum. In underfed females, GnRH I had an
      effect on short-term food intake that was intermediate to saline and GnRH II. We
      conclude that, in addition to its permissive role in regulating reproduction,
      GnRH II may also modulate food intake in mammals. Because GnRH II is present in
      primate brain, it may also serve a similar function in humans.

PMID- 14576177
TI  - Low-dose immunization with adenovirus expressing the thyroid-stimulating hormone
      receptor A-subunit deviates the antibody response toward that of autoantibodies
      in human Graves' disease.
AB  - Immunization with adenovirus expressing the TSH receptor (TSHR) induces
      hyperthyroidism in 25-50% of mice. Even more effective is immunization with a
      TSHR A-subunit adenovirus (65-84% hyperthyroidism). Nevertheless, TSHR antibody
      characteristics in these mice do not mimic accurately those of autoantibodies in
      typical Graves' patients, with a marked TSH-blocking antibody response. We
      hypothesized that this suboptimal antibody response was consequent to the
      standard dose of TSHR-adenovirus providing too great an immune stimulus. To test
      this hypothesis, we compared BALB/c mice immunized with the usual number (10(11))
      and with far fewer viral particles (10(9) and 10(7)). Regardless of viral dose,
      hyperthyroidism developed in a similar proportion (68-80%) of mice. We then
      examined the qualitative nature of TSHR antibodies in each group. Sera from all
      mice had TSH binding-inhibitory (TBI) activity after the second immunization,
      with TBI values in proportion to the viral dose. After the third injection, all
      groups had near-maximal TBI values. Remarkably, in confirmation of our
      hypothesis, immunization with progressively lower viral doses generated TSHR
      antibodies approaching the characteristics of autoantibodies in human Graves'
      disease as follows: 1) lower TSHR antibody titers on ELISA and 2) lower TSH
      blocking antibody activity without decrease in thyroid-stimulating antibody
      activity. In summary, low-dose immunization with adenovirus expressing the free
      TSHR A-subunit provides an induced animal model with a high prevalence of
      hyperthyroidism as well as TSHR antibodies more closely resembling autoantibodies
      in Graves' disease.

PMID- 14576178
TI  - Does cortisol inhibit pulsatile luteinizing hormone secretion at the hypothalamic
      or pituitary level?
AB  - Elevations in glucocorticoids suppress pulsatile LH secretion in sheep, but the
      neuroendocrine sites and mechanisms of this disruption remain unclear. Here, we
      conducted two experiments in ovariectomized ewes to determine whether an acute
      increase in plasma cortisol inhibits pulsatile LH secretion by suppressing GnRH
      release into pituitary portal blood or by inhibiting pituitary responsiveness to
      GnRH. First, we sampled pituitary portal and peripheral blood after
      administration of cortisol to mimic the elevation stimulated by an
      immune/inflammatory stress. Within 1 h, cortisol inhibited LH pulse amplitude. LH
      pulse frequency, however, was unaffected. In contrast, cortisol did not suppress
      either parameter of GnRH secretion. Next, we assessed the effect of cortisol on
      pituitary responsiveness to exogenous GnRH pulses of fixed amplitude, duration,
      and frequency. Hourly pulses of GnRH were delivered to ewes in which endogenous
      GnRH secretion was blocked by estradiol. Cortisol, again, rapidly and robustly
      suppressed the amplitude of GnRH-induced LH pulses. We conclude that, in the
      ovariectomized ewe, cortisol suppresses pulsatile LH secretion by inhibiting
      pituitary responsiveness to GnRH rather than by suppressing hypothalamic GnRH
      release.

PMID- 14576179
TI  - A transgenic mouse with a deletion in the collagenous domain of adiponectin
      displays elevated circulating adiponectin and improved insulin sensitivity.
AB  - Adiponectin is a plasma protein expressed exclusively in adipose tissue.
      Adiponectin levels are linked to insulin sensitivity, but a direct effect of
      chronically elevated adiponectin on improved insulin sensitivity has not yet been
      demonstrated. We identified a dominant mutation in the collagenous domain of
      adiponectin that elevated circulating adiponectin values in mice by 3-fold.
      Adiponectinemia raised lipid clearance and lipoprotein lipase activity, and
      suppressed insulin-mediated endogenous glucose production. The induction of
      adiponectin during puberty and the sexual dimorphism in adult adiponectin values
      were preserved in these transgenic animals. As a result of elevated adiponectin,
      serum PRL values and brown adipose mass both increased. The effects on
      carbohydrate and lipid metabolism were associated with elevated phosphorylation
      of 5'-AMP-activated protein kinase in liver and elevated expression of
      peroxisomal proliferator-activated receptor gamma2, caveolin-1, and mitochondrial
      markers in white adipose tissue. These studies strongly suggest that increasing
      endogenous adiponectin levels has direct effects on insulin sensitivity and may
      induce similar physiological responses as prolonged treatment with peroxisomal
      proliferator-activated receptor gamma agonists.

PMID- 14576180
TI  - Nuclear factor-kappaB activates transcription of the androgen receptor gene in
      Sertoli cells isolated from testes of adult rats.
AB  - The androgen receptor (AR) in Sertoli cells mediates the actions of testosterone
      on spermatogenesis. However, the transcription factors responsible for AR gene
      regulation in Sertoli cells remain unknown. In this study, we determined that
      nuclear factor-kappaB (NF-kappaB) regulates transcription of AR in primary
      cultures of Sertoli cells isolated from testes of adult rats. Electrophoretic
      mobility shift and antibody supershift assays with nuclear extracts prepared from
      Sertoli cells identified two binding sites, termed kappaB1 at -491/-482 bp and
      kappaB2 at -574/-565 bp, upstream of the transcription start site of the AR gene
      that bind the NF-kappaB subunits, p50 and p65. DNAse I footprint analyses showed
      that binding of the p50 NF-kappaB subunit protected the same regions on the rat
      AR promoter. Analyses of AR promoter-luciferase reporter gene activity after
      transfection of primary cultures of Sertoli cells demonstrated that mutation of
      the kappaB2 site or combined mutation of the kappaB1 and kappaB2 sites reduced
      activity by 40%. Preferential binding of the transcriptionally active p65/p50
      heterodimer to the kappaB2 site rather than to the kappaB1 site supported these
      observations. Overexpression of the NF-kappaB p65 and p50 subunits in Sertoli
      cells increased activity from the wild-type AR promoter and the promoter with
      mutation of the kappaB1 site, but not the kappaB2 site. Activity was further
      stimulated by CBP (CREB binding protein), a coactivator of p65 transcriptional
      activity. Taken together, our data show that NF-kappaB is an activator of AR gene
      transcription in Sertoli cells and may be an important determinant of androgen
      activity during spermatogenesis.

PMID- 14576181
TI  - Desensitization and endocytosis mechanisms of ghrelin-activated growth hormone
      secretagogue receptor 1a.
AB  - In this study, a sequential analysis of pathways involved in the regulation of GH
      secretagogue receptor subtype 1a (GHSR-1a) signaling has been undertaken to
      characterize the process of rapid desensitization that is observed after ghrelin
      binding. This process was evaluated by studying the binding of [(125)I]ghrelin,
      measurement of intracellular calcium mobilization, and confocal microscopy. The
      results indicate that GHSR-1a is mainly localized at the plasma membrane under
      unstimulated conditions and rapidly desensitizes after stimulation. The agonist
      dependent desensitization is not mediated by protein kinase C because phorbol
      ester, phorbol-12-myristate-13-acetate, failed to block the ghrelin-induced
      calcium response. The ghrelin/GHSR-1a complex progressively disappears from the
      plasma membrane after 20 min exposure to ghrelin and accumulates in the
      perinuclear region after 60 min. Colocalization of the internalized GHSR-1a with
      the early endosome marker (EEA1) after 20 min exposure to ghrelin suggests that
      endocytosis occurs via clathrin-coated pits, which is consistent with the lack of
      internalization of this receptor observed after potassium depletion. Different
      from other G protein-coupled receptors, GHSR-1a showed slow recycling. Surface
      binding slowly recovered after agonist treatment and returned to control levels
      within 360 min. Furthermore, inhibition of vacuolar H(+)-ATPases prevented
      recycling of the receptor, suggesting that the nondissociation of the
      ligand/receptor complex is responsible for this effect. The GHSR-1a
      internalization may explain the characteristic physiological responses mediated
      by this receptor.

PMID- 14576182
TI  - Valproate potentiates androgen biosynthesis in human ovarian theca cells.
AB  - In patients with epilepsy, treatment with valproate (VPA) has been reported to be
      associated with polycystic ovary syndrome-like symptoms including weight gain,
      hyperandrogenemia, and hyperinsulinemia. We examined the effect of VPA on
      androgen biosynthesis in ovarian theca cells isolated from follicles of normal
      cycling women to determine whether the hyperandrogenemia reported with VPA
      treatment could be a result of direct effects of VPA on the ovary. In long-term
      cultures of theca cells treated for 72 h with sodium valproate (30-3000 microm),
      we observed an increase in basal and forskolin-stimulated dehydroepiandrosterone
      (DHEA), androstenedione, and 17alpha-hydroxyprogesterone production compared with
      control values. In contrast, low doses of VPA treatment (i.e. 30-300 microm) had
      no effect on basal and forskolin-stimulated progesterone production, whereas
      higher doses of VPA (1000-3000 microm) inhibited progesterone production. The
      most pronounced effect of VPA on androgen biosynthesis was observed in the dose
      range of 300-3000 microm, which represent therapeutic levels in the treatment of
      epilepsy and bipolar disorder. Western analyses demonstrated that VPA treatment
      increased both basal and forskolin-stimulated P450c17 and P450scc protein levels,
      whereas the amount of steroidogenic acute regulatory protein was unaffected. In
      transient transfection studies, VPA was found to increase P450 17alpha
      hydroxylase and P450 cholesterol side-chain cleavage promoter activity, whereas
      steroidogenic acute regulatory protein promoter activity was unaffected.
      Consistent with the ability of VPA to act as a histone deacetylase (HDAC)
      inhibitor in other cell systems, VPA (500 microm) treatment was observed to
      increase histone H3 acetylation and P450 17alpha-hydroxylase mRNA accumulation.
      The HDAC inhibitor butyric acid (500 microm) similarly increased histone H3
      acetylation and DHEA biosynthesis, whereas the VPA derivative valpromide (500
      microm), which lacks HDAC inhibitory activity, had no effect on histone
      acetylation or DHEA biosynthesis. These data suggest that VPA-induced ovarian
      androgen biosynthesis results from changes in chromatin modifications (histone
      acetylation) that augment transcription of steroidogenic genes. These studies
      provide the first biochemical evidence to support a role for VPA in the genesis
      of polycystic ovary syndrome-like symptoms, and establish a direct link between
      VPA treatment and increased ovarian androgen biosynthesis.

PMID- 14576183
TI  - The axolotl (Ambystoma mexicanum), a neotenic amphibian, expresses functional
      thyroid hormone receptors.
AB  - Neotenic amphibians such as the axolotl (Ambystoma mexicanum) are often unable to
      undergo metamorphosis under natural conditions. It is thought that neoteny
      represents a deviation from the standard course of amphibian ontogeny, affecting
      the thyroid axis at different levels from the central nervous system to
      peripheral organs. Thyroid hormone receptors (TRs) that bind the thyroid hormone
      (TH) T(3) have been described in axolotl. However, the full sequences of TR were
      needed to better characterize the TH response and to be able to assess their
      functional capacity at the molecular level. We report that each of the alpha and
      beta axolotl TRs bind both DNA and TH, and they activate transcription in
      response to TH in a mammalian cell-based transient transfection assay. Moreover,
      both TRs are expressed in axolotl tissues. Interestingly, each TR gene generates
      alternatively spliced isoforms, harboring partial or total deletions of the
      ligand-binding domain, which are expressed in vivo. Further, we found that in the
      axolotl, TH regulates the expression of stromelysin 3 and collagenase 3, which
      are TH target genes in Xenopus. Taken together, these results suggest that
      axolotl TRs are functional and that the molecular basis of neoteny in the axolotl
      is not linked to a major defect in TH response in peripheral tissues.

PMID- 14576184
TI  - Cell-specific pituitary gene expression profiles after treatment with leukemia
      inhibitory factor reveal novel modulators for proopiomelanocortin expression.
AB  - Leukemia inhibitory factor (LIF) mediates the hypothalamo-pituitary-adrenal
      stress response. Transgenic mice overexpressing LIF in the developing pituitary
      have altered pituitary differentiation with expansion of corticotropes,
      maintenance of Rathke's cleft cysts, and suppression of all other pituitary cell
      types. Affymetrix GeneChips were used to identify modulators of LIF effects in
      corticotrope (AtT-20) and somatolactotrope (GH(3)) cells. In addition to genes
      known to respond to LIF in corticotrope cells [e.g. suppressor of cytokine
      signaling-3 (SOCS-3), signal transducer and activator of transcription-3, SH2
      domain-containing tyrosine phosphatase-1, and proopiomelanocortin (POMC)],
      corticotrope-specific changes were also observed for genes involved in glycolysis
      and gluconeogenesis, transcription factors, signaling molecules, and expressed
      sequence tags. Two transcription factors identified, CCAAT/enhancer-binding
      protein beta (C/EBPbeta) and glial cell-derived neurotrophic factor (GDNF)
      inducible factor (GIF), dose-dependently induced expression of the rat POMC
      promoter when overexpressed in AtT-20 cells. LIF further induced POMC
      transcription with C/EBPbeta, but not with GIF. C/EBPbeta also induced expression
      of the SOCS-3 promoter that was further enhanced by cotreatment with LIF.
      However, GIF did not affect SOCS-3 expression. These results indicate that
      C/EBPbeta and GIF are downstream effectors of LIF corticotrope action. LIF also
      stimulates the expression of inhibitors of its actions, such as SOCS-3 and SH2
      domain-containing tyrosine phosphatase-1. alpha(2)-HS-glycoprotein (AHSG)/fetuin,
      a secreted protein that antagonizes bone TGFbeta/bone morphogenic protein
      signaling, was induced by LIF in a signal transducer and activator of
      transcription-3-dependent fashion. Pretreatment with AHSG/fetuin blocked LIF
      induced expression of the POMC promoter independently of SOCS-3. Thus, using
      GeneChips, C/EBPbeta and GIF have been identified as novel mediators and
      AHSG/fetuin as an inhibitor of LIF action in corticotropes.

PMID- 14576185
TI  - Galanin-like peptide stimulates the release of gonadotropin-releasing hormone in
      vitro and may mediate the effects of leptin on the hypothalamo-pituitary-gonadal
      axis.
AB  - Leptin regulates the hypothalamo-pituitary-gonadal axis in relation to
      nutritional status. The mechanism through which leptin mediates its effects on
      neuroendocrine reproductive circuits remains unclear. Galanin-like peptide (GALP)
      is a recently identified hypothalamic peptide, localized in the arcuate nucleus,
      which seems to be regulated by leptin and stimulates LH when administered
      centrally. Here, we demonstrate that leptin stimulates the release of GALP and
      GnRH in vitro from hypothalamic explants harvested from male rats. In addition,
      we show that GALP stimulates the release of GnRH from hypothalamic explants and
      GT1-7 cells. Furthermore, we demonstrate that GALP antiserum blocks the
      stimulatory action of leptin on GnRH release from hypothalamic explants. GALP is
      a ligand of the galanin receptors. We therefore investigated whether the effect
      of GALP on GnRH release may be mediated via a known galanin receptor. GALP
      stimulated GnRH release from hypothalamic explants was attenuated (but not
      abolished) by the galanin receptor antagonist galantide. However, GALP-stimulated
      GnRH release from GT1-7 cells was not diminished by the coadministration of
      galantide. In addition, none of the cloned galanin receptors were expressed in
      GT1-7 cells by RT-PCR. These observations suggest that GALP may stimulate GnRH
      release through an indirect pathway involving a galanin receptor and via a direct
      action on GnRH neurons, possibly through a novel receptor. These findings suggest
      that GALP may mediate the actions of leptin on the reproductive axis and provide
      a link between nutrition and fertility.

PMID- 14576186
TI  - Biosynthesis of proopiomelanocortin-derived peptides in prohormone convertase 2
      and 7B2 null mice.
AB  - Prohormone convertases (PCs) are thought to represent the major proteinases
      involved in the biosynthetic processing of peptide hormone precursors to
      bioactive peptide products. The maturation of PC2 requires the aid of a helper
      protein, 7B2, in order for the zymogen to become an active enzyme species. The
      7B2 and PC2 nulls should thus be functionally equivalent with regard to deficits
      in precursor processing. In this article, we have examined this proposition
      through the study of proopiomelanocortin (POMC) biosynthesis and granule content
      in both null models. RIA data indicate that both PC2 and 7B2 nulls lack pituitary
      alpha-MSH; interestingly, 7B2 nulls are still able to generate beta-endorphin
      from beta-lipotropin, whereas PC2 nulls contain little if any beta-endorphin.
      Labeling experiments demonstrate a build-up of POMC, high molecular weight
      intermediates, and intact ACTH, as well as the disappearance of alpha-MSH, in
      both null models. Electron microscopy of neurointermediate lobe melanotrophs
      reveals the presence of a significantly greater number of secretory granules in
      both 7B2 and PC2 nulls compared with wild-type controls. However, PC2 null
      melanotrophs contain twice as many granules as 7B2 null melanotrophs. Another
      difference between the two null models is a relatively enhanced accumulation of
      precursors in the PC2 null compared with the 7B2 null; these include not only PC2
      substrates, but also presumed PC1 substrates. These data indicate that the two
      nulls are not phenotypically equivalent.

PMID- 14576187
TI  - Corticotropin-releasing hormone and its structurally related urocortin are
      synthesized and secreted by human mast cells.
AB  - Stress activates the hypothalamic-pituitary-adrenal axis through CRH, leading to
      production of glucocorticoids that down-regulate immune responses. However, acute
      stress also has proinflammatory effects. We previously showed that restraint
      stress, as well as CRH and its structurally related urocortin (Ucn), could
      activate mast cells and trigger mast cell-dependent vascular permeability. Here
      we show for the first time that human cord blood-derived cultured mast cells
      (hCBMC) at 10 wk, but not at 2 wk, are immunocytochemically positive for CRH and
      Ucn; human leukemic mast cells are weakly positive for both peptides. The ability
      of these mast cells to synthesize CRH and Ucn was confirmed by showing mRNA
      expression with RT-PCR. hCBMC (8-14 wk) synthesize and store 1-10 ng/106 cells
      (10-20 microg/g) of both CRH and Ucn detected by ELISA of cell homogenates.
      Stimulation of IgE-sensitized hCBMC with anti-IgE results in secretion of most
      CRH and Ucn. These findings indicate that mast cells are not only the target, but
      also a potential source of CRH and Ucn that could have both autocrine and
      paracrine functions, especially in allergic inflammatory disorders exacerbated by
      stress.

PMID- 14576188
TI  - Expression and distribution of MAL2, an essential element of the machinery for
      basolateral-to-apical transcytosis, in human thyroid epithelial cells.
AB  - Polarized transport of newly synthesized proteins to the apical surface of
      epithelial cells takes place by a direct pathway from the Golgi or by an indirect
      route involving the delivery of the protein to the basolateral surface, followed
      by its endocytosis and transport across the cell. The indirect pathway, named
      transcytosis, is also used to translocate external material across the cell. MAL,
      a raft-associated integral membrane protein required for the direct apical route,
      is known to be expressed in the thyroid epithelium. MAL2, a member of the MAL
      protein family, has been recently identified as an essential component of the
      machinery for the transcytotic route in human hepatoma cells. Herein, we have
      investigated the expression and distribution of MAL2 in the human thyroid. MAL2
      mRNA species were detected in the thyroid. Immunohistochemical analysis of
      thyroid follicles indicated that, in contrast to MAL, which predominantly
      distributed to the Golgi region, MAL2 distributed to the apical membrane.
      Biochemical analysis in primary thyrocyte cultures indicated that MAL2
      exclusively resides in raft membranes. Confocal immunofluorescence analysis of
      thyrocyte cultures revealed that MAL2 predominantly localized in a subapical
      endosome compartment that was positive for Rab11a. Alterations in MAL2
      expression, distribution, and appearance were found in specific types of
      follicular cell-derived carcinomas. Although the role of MAL2 has not been
      directly addressed in this study, the simultaneous expression of MAL and MAL2
      suggests that traffic to the apical membrane in thyrocytes may rely on MAL for
      the direct route and on MAL2 for the transcytotic pathway.

PMID- 14576189
TI  - Dose-dependent switch in response of gonadotropin-releasing hormone (GnRH)
      neurons to GnRH mediated through the type I GnRH receptor.
AB  - Pulsatile release of GnRH provides central control of reproduction. GnRH neuron
      activity is likely synchronized to produce hormone pulses, but the mechanisms are
      largely unknown. One candidate for communication among these neurons is GnRH
      itself. Cultured embryonic and immortalized GnRH neurons express GnRH receptor
      type I (GnRHR-1), but expression has not been shown in adult GnRH neurons. Using
      mice that express green fluorescent protein (GFP) in GnRH neurons, we tested
      whether adult GnRH neurons express GnRHR-1. GFP-positive (n = 42) and -negative
      neurons (n = 22) were harvested from brain slices, and single-cell RT-PCR was
      performed with cell contents. Fifty-two percent of the GnRH neurons tested
      expressed GnRHR-1, but only 9% of non-GnRH hypothalamic neurons expressed GnRHR
      1; no false harvest controls (n = 13) were positive. GnRHR-1 expression within
      GnRH neurons suggested a physiological ultrashort loop feedback role for GnRH.
      Thus, we examined the effect of GnRH on the firing rate of GnRH neurons. Low-dose
      GnRH (20 nm) significantly decreased firing rate in 12 of 22 neurons (by 42 +/-
      4%, P < 0.05), whereas higher doses increased firing rate (200 nm, five of 10
      neurons, 72 +/- 26%; 2000 nm, nine of 13 neurons, 53 +/- 8%). Interestingly, the
      fraction of GnRH neurons responding was similar to the fraction in which GnRHR-1
      was detected. Together, these data demonstrate that a subpopulation of GnRH
      neurons express GnRHR-1 and respond to GnRH with altered firing. The dose
      dependence suggests that this autocrine control of GnRH neurons may be not only a
      mechanism for generating and modulating pulsatile release, but it may also be
      involved in the switch between pulse and surge modes of release.

PMID- 14576190
TI  - Fetal programming: prenatal testosterone excess leads to fetal growth retardation
      and postnatal catch-up growth in sheep.
AB  - Alterations in the maternal endocrine, nutritional, and metabolic environment
      disrupt the developmental trajectory of the fetus, leading to adult diseases.
      Female offspring of rats, subhuman primates, and sheep treated prenatally with
      testosterone (T) develop reproductive/metabolic defects during adult life similar
      to those that occur after intrauterine growth retardation. In the present study
      we determined whether prenatal T treatment produces growth-retarded offspring.
      Cottonseed oil or T propionate (100 mg, im) was administered twice weekly to
      pregnant sheep between 30-90 d gestation (term = 147 d; cottonseed oil, n = 16;
      prenatal T, n = 32). Newborn weight and body dimensions were measured the day
      after birth, and postnatal weight gain was monitored for 4 months in all females
      and in a subset of males. Consistent with its action, prenatal T treatment
      produced females and males with greater anogenital distances relative to
      controls. Prenatal T treatment reduced body weights and heights of newborns from
      both sexes and chest circumference of females. Prenatally T-treated females, but
      not males, exhibited catch-up growth during 2-4 months of postnatal life. Plasma
      IGF-binding protein-1 and IGF-binding protein-2, but not IGF-I, levels of
      prenatally T-treated females were elevated in the first month of life, a period
      when the prenatally T-treated females were not exhibiting catch-up growth. This
      is suggestive of reduced IGF availability and potential contribution to growth
      retardation. These findings support the concept that fetal growth retardation and
      postnatal catch-up growth, early markers of future adult diseases, can also be
      programmed by prenatal exposure to excess sex steroids.

PMID- 14576191
TI  - Attenuation by reactive oxygen species of glucocorticoid suppression on
      proopiomelanocortin gene expression in pituitary corticotroph cells.
AB  - Up-regulation of hypothalamo-pituitary-adrenal axis is maintained during acute
      inflammation and/or infection, in the face of sustained elevation of plasma
      glucocorticoid hormone. Inflammatory stress is usually associated with high
      plasma cytokine levels and increased generation of reactive oxygen species (ROS)
      as well. In this study, we examined the effect of ROS on the negative feedback
      regulation of glucocorticoid in hypothalamo-pituitary-adrenal axis using AtT20
      corticotroph cells in vitro. When the cells were treated with H2O2,
      glucocorticoid suppression on the proopiomelanocortin gene promoter activity was
      attenuated in a dose-dependent manner. H2O2 also inhibited the ligand-stimulated
      nuclear translocation of glucocorticoid receptor. The released glucocorticoid
      suppression by H2O2 was not observed when the cells were cotreated with
      antioxidants. Together, these results suggest that increased ROS generation in
      the oxidative redox state attenuates the glucocorticoid negative feedback system,
      at least in part, by interfering with the nuclear translocation of glucocorticoid
      receptor and eliminating the repression on proopiomelanocortin gene expression.

PMID- 14576192
TI  - Transcriptional regulation of P450scc gene expression in the embryonic rodent
      nervous system.
AB  - Steroid hormones are synthesized in adrenals, gonads, placenta, and the central
      and peripheral nervous systems (neurosteroids). Neurosteroidogenesis, like
      conventional steroidogenesis, begins with the conversion of cholesterol to
      pregnenolone, catalyzed by mitochondrial P450 side-chain cleavage enzyme
      (P450scc). Transcription of the P450scc gene in the adrenals and gonads requires
      steroidogenic factor-1, which is not expressed in the nervous system cells that
      express P450scc. A crucial transcriptional regulatory region of the rat P450scc
      gene is at -130/-94. We have purified two nuclear proteins (70 and 86 kDa) from
      rat glial C6 cells that specifically bind to the -130/-94 region of the rat
      P450scc promoter and identified them as the DNA-binding subunits of autoimmune
      antigen Ku. Ku colocalized with P450scc in several regions of the nervous system,
      but its overexpression in C6 cells did not augment transcription from a -130/-94
      Luciferase construct. Members of the Sp family of transcription factors also bind
      to the same DNA sequence as Ku. Sp4 and Sp2 colocalize with P450scc in the
      nervous system early in development, whereas Sp1 and Sp4 colocalize later in
      development. Sp1 robustly increased transcription from this element in Sp
      deficient Drosophila SL2 cells, and Ku synergistically enhanced this Sp1
      stimulated transcription. Thus, members of the Sp transcription family play a
      role in activating P450scc gene transcription in the nervous system, and Ku may
      further augment this activation.

PMID- 14576193
TI  - Tumor necrosis factor-mediated E2F1 suppression in endothelial cells:
      differential requirement of c-Jun N-terminal kinase and p38 mitogen-activated
      protein kinase signal transduction pathways.
AB  - After balloon angioplasty, locally expressed tumor necrosis factor (TNF)-alpha
      disrupts endothelial cell (EC) proliferation and reendothelialization of the
      injured vessel. We have previously reported that TNF inhibits the EC cycle and
      downregulates the transcription factor E2F1. Ectopic expression of E2F1 at the
      site of injury improves reendothelialization of the injured vessel. In this
      study, we report that c-Jun N-terminal kinase (JNK) 1 and p38 mitogen-activated
      protein kinases (MAPKs) are differentially required for E2F1 expression and
      activity in ECs. Overexpression of constitutively active JNK1 mimicked TNF
      mediated inhibitory events, whereas dominant-negative JNK1 prevented these
      effects. E2F cis elements in the promoter of E2F1 gene mediate suppressive
      actions of TNF, because removal of these sites rendered E2F1 promoter activity
      insensitive to TNF. JNK1 physically interacted with E2F1 and inactivated it via
      direct phosphorylation. Additionally, TNF inhibited Rb phosphorylation and
      dissociation from E2F1. Overexpression of constitutively active p38 MAPK
      facilitated Rb-E2F1 dissociation, whereas that of dominant-negative p38 MAPK did
      not. Taken together, these data suggest a differential requirement of JNK1 and
      p38 MAPK in TNF regulation of E2F1. Targeted inactivation of JNK1 at arterial
      injury sites may represent a potential therapeutic intervention for ameliorating
      TNF-mediated EC dysfunction.

PMID- 14576194
TI  - AlphaB-crystallin modulates protein aggregation of abnormal desmin.
AB  - AlphaB-crystallin (CryAB) is the most abundant small heat shock protein in the
      heart. Upregulation of CryAB in desmin-related myopathy and its downregulation in
      end-stage congestive heart failure have both been reported. We previously
      demonstrated via cardiac-specific transgenesis that modest increases in normal
      CryAB are not detrimental to the heart, whereas expression of the R120G mutation
      of CryAB caused a desminopathy. It is generally believed that CryAB plays an
      important role in protecting the intermediate filaments, but the underlying
      mechanism is unclear. We hypothesized that CryAB protects the desmin filaments
      via preventing abnormal desmin protein from aggregating adversely. To test this
      hypothesis in vivo, mice expressing a desmin mutation that causes a desmin
      related cardiomyopathy (D7) were bred into the R120G-CryAB transgenic (TG)
      background to examine the accumulation and aberrant aggregation of desmin
      protein. Despite lower mRNA expression of D7-des than in the D7-des TG hearts,
      the double-TG myocardium exhibited significantly higher desmin protein levels and
      dramatically more aberrant desmin aggregates than the D7-des TG hearts. The
      double-TG mice displayed a significantly stronger cardiac hypertrophic response,
      with the mice dying of congestive heart failure before 7 weeks. To explore the
      ability of wild-type (WT) CryAB to protect against mutant desmin, a desmin mutant
      was expressed in both the conventional and WT-CryAB stably transfected HEK cells.
      Significantly less aberrant desmin aggregation was observed in the WT-CryAB
      overexpressing cells than in the HEK cells. The results suggest that CryAB
      modulates abnormal desmin aggregation and can serve a cardioprotective role.

PMID- 14576196
TI  - Influence of Na+-independent Cl--HCO3- exchange on the slow force response to
      myocardial stretch.
AB  - Previous work demonstrated that the slow force response (SFR) to stretch is due
      to the increase in calcium transients (Ca2+T) produced by an autocrine-paracrine
      mechanism of locally produced angiotensin II/endothelin activating Na+-H+
      exchange. Although a rise in pHi is presumed to follow stretch, it was observed
      only in the absence of extracellular bicarbonate, suggesting pHi compensation
      through the Na+-independent Cl--HCO3- exchange (AE) mechanism. Because available
      AE inhibitors do not distinguish between different bicarbonate-dependent
      mechanisms or even between AE isoforms, we developed a functional inhibitory
      antibody against both the AE3c and AE3fl isoforms (anti-AE3Loop III) that was
      used to explore if pHi would rise in stretched cat papillary muscles superfused
      with bicarbonate after AE3 inhibition. In addition, the influence of this
      potential increase in pHi on the SFR was analyzed. In this study, we present
      evidence that cancellation of AE3 isoforms activity (either by superfusion with
      bicarbonate-free buffer or with anti-AE3Loop III) results in pHi increase after
      stretch and the magnitude of the SFR was larger than when AE was operative,
      despite of similar increases in [Na+]i and Ca2+T under both conditions.
      Inhibition of reverse mode Na+-Ca2+ exchange reduced the SFR to the half when the
      AE was inactive and totally suppressed it when AE3 was active. The difference in
      the SFR magnitude and response to inhibition of reverse mode Na+-Ca2+ exchange
      can be ascribed to a pHi-induced increase in myofilament Ca2+ responsiveness.

PMID- 14576197
TI  - Alteration of NMDA NR1 receptors within the paraventricular nucleus of
      hypothalamus in rats with heart failure.
AB  - One of the pathophysiological characteristics of chronic heart failure (HF) is
      elevated sympathetic drive, which is a major factor contributing to the morbidity
      and mortality of HF. Resent evidence points to a central mechanism that
      contributes to the sympathetic abnormality in HF. The paraventricular nucleus
      (PVN) of the hypothalamus is an important site that integrates sympathetic nerve
      activity. Studies have shown that glutamate elicits excitatory effects on neurons
      in the PVN through the NMDA receptor. The goal of the present study was to
      examine the role of NMDA receptors in the altered sympathetic nerve activation
      during HF. The left coronary ligation-induced heart failure model in the rat was
      used. In alpha-chloralose and urethane anesthetized rats, microinjection of NMDA
      into the PVN (50 to 200 pmol) produced dose-dependent increases in renal
      sympathetic nerve discharge (RSND), arterial blood pressure (BP), and heart rate
      (HR). This response to NMDA was significantly potentiated (27+/-7%) in HF
      compared with sham rats. On the other hand, microinjection of the NMDA receptor
      antagonist AP-5 (4 to 16 nmol) into the PVN caused significant decreases in RSND,
      BP, and HR only in rats with HF but very slight changes in sham rats.
      Furthermore, using microdialysis and HPLC in combination with electrochemical
      detection techniques, we found that the glutamate level in the PVN was not
      increased significantly in HF compared with sham rats. However, using RT-PCR,
      Western blot, and immunofluorescence techniques, it was found that NMDA NR1
      subunit mRNA expression and protein level in the PVN were significantly increased
      in HF compared with sham rats. These data suggest that the increased
      glutamatergic activity on sympathetic regulation, due to the upregulation of NMDA
      NR1 receptor subunits within the PVN may contribute to the elevated
      sympathoexcitation during HF.

PMID- 14576198
TI  - Pharmacological activation of normal and arrhythmia-associated mutant KCNQ1
      potassium channels.
AB  - KCNQ1 alpha-subunits coassemble with KCNE1 beta-subunits to form channels that
      conduct the slow delayed rectifier K+ current (IKs) important for repolarization
      of the cardiac action potential. Mutations in KCNQ1 reduce IKs and cause long-QT
      syndrome, a disorder of ventricular repolarization that predisposes affected
      individuals to arrhythmia and sudden death. Current therapy for long-QT syndrome
      is inadequate. R-L3 is a benzodiazepine that activates IKs and has the potential
      to provide gene-specific therapy. In the present study, we characterize the
      molecular determinants of R-L3 interaction with KCNQ1 channels, use computer
      modeling to propose a mechanism for drug-induced changes in channel gating, and
      determine its effect on several long-QT syndrome-associated mutant KCNQ1 channels
      heterologously expressed in Xenopus oocytes. Scanning mutagenesis combined with
      voltage-clamp analysis indicated that R-L3 interacts with specific residues
      located in the 5th and 6th transmembrane domains of KCNQ1 subunits. Most KCNQ1
      mutant channels responded to R-L3 similarly to wild-type channels, but one mutant
      channel (G306R) was insensitive to R-L3 possibly because it disrupted a key
      component of the drug-binding site.

PMID- 14576195
TI  - Aldosteronism and peripheral blood mononuclear cell activation: a neuroendocrine
      immune interface.
AB  - Aldosteronism eventuates in a proinflammatory/fibrogenic vascular phenotype of
      the heart and systemic organs. It remains uncertain whether peripheral blood
      mononuclear cells (PBMCs) are activated before tissue invasion by
      monocytes/macrophages and lymphocytes, as is the case for responsible pathogenic
      mechanisms. Uninephrectomized rats treated for 4 weeks with dietary 1% NaCl and
      aldosterone (ALDOST, 0.75 microg/h) with or without spironolactone (Spi, 100
      mg/kg per daily gavage) were compared with unoperated/untreated and
      uninephrectomized/salt-treated controls. Before intramural coronary vascular
      lesions appeared at week 4 of ALDOST, we found (1) a reduction of PBMC cytosolic
      free [Mg2+]i, together with intracellular Mg2+ and Ca2+ loading, whereas plasma
      and cardiac tissue Mg2+ were no different from controls; (2) increased H2O2
      production by monocytes and lymphocytes together with upregulated PBMC gene
      expression of oxidative stress-inducible tyrosine phosphatase and Mn2+-superoxide
      dismutase and the presence of 3-nitrotyrosine in CD4+ and ED-1-positive
      inflammatory cells that had invaded intramural coronary arteries; (3) B-cell
      activation, including transcription of immunoglobulins, intracellular adhesion
      molecule-1, and CC and CXC chemokines and their receptors; (4) expansion of B
      lymphocyte subset and myosin heavy chain class II-expressing lymphocytes; and (5)
      autoreactivity with gene expression for antibodies to acetylcholine receptors and
      a downregulation of RT-6.2, which is in keeping with cell activation and
      associated with autoimmunity. Spi cotreatment attenuated the rise in
      intracellular Ca2+, the appearance of oxidative/nitrosative stress in PBMCs and
      invading inflammatory cells, and alterations in PBMC transcriptome. Thus,
      aldosteronism is associated with an activation of circulating immune cells
      induced by iterations in PBMC divalent cations and transduced by
      oxidative/nitrosative stress. ALDO receptor antagonism modulates this
      neuroendocrine-immune interface. The full text of this article is available
      online at http://www.circresaha.org.

PMID- 14576199
TI  - Mechanisms of hepatocyte growth factor-mediated vascular smooth muscle cell
      migration.
AB  - The migration of vascular smooth muscle cells (SMCs) from the media into the
      neointima and their subsequent proliferation is important in the pathogenesis of
      atherosclerosis. This process is regulated by multiple factors, including growth
      factors, and involves changes in the interaction of SMCs with the extracellular
      matrix and in intracellular signaling cascades that regulate cell movement. We
      demonstrated previously that hepatocyte growth factor (HGF) is expressed in human
      atherosclerotic plaques. Although HGF has been shown to promote SMC migration,
      the mechanisms involved in this process have not been characterized fully. In
      this study, inhibitory antibodies were used to determine which integrins mediated
      HGF-induced SMC migration. Inhibition of beta1 or beta3 integrin resulted in a
      significant decrease in migration. Subsequent experiments were performed to
      characterize additional biochemical mechanisms involved in HGF-mediated
      migration. HGF induced the redistribution of focal adhesions, the activation of
      focal adhesion kinase (FAK) and proline-rich tyrosine kinase 2 (Pyk2) and their
      increased association with beta1 and beta3 integrins, and the production of pro
      matrix metalloproteinase-2. Migration levels were significantly reduced by
      cotreatment of SMCs with the extracellular signal-regulated kinase 1/2 (ERK1/2)
      inhibitor, UO126, the p38 inhibitor, SB203580, or the phosphatidylinositol-3
      kinase inhibitor, LY294002. In HGF-treated SMCs, focal adhesion redistribution
      and FAK and Pyk2 activation were decreased by ERK1/2 inhibition. Neither SB203580
      nor LY294002 inhibited HGF-induced ERK1/2 activation. Thus, ERK1/2 signaling may
      play an important role in HGF-mediated SMC migration by contributing to focal
      adhesion redistribution and FAK and Pyk2 activation.

PMID- 14576200
TI  - Cell type-specific regulation of angiogenic growth factor gene expression and
      induction of angiogenesis in nonischemic tissue by a constitutively active form
      of hypoxia-inducible factor 1.
AB  - Understanding molecular mechanisms regulating angiogenesis may lead to novel
      therapies for ischemic disorders. Hypoxia-inducible factor 1 (HIF-1) activates
      vascular endothelial growth factor (VEGF) gene expression in hypoxic/ischemic
      tissue. In this study we demonstrate that exposure of primary cultures of cardiac
      and vascular cells to hypoxia or AdCA5, an adenovirus encoding a constitutively
      active form of HIF-1alpha, modulates the expression of genes encoding the
      angiogenic factors angiopoietin-1 (ANGPT1), ANGPT2, placental growth factor, and
      platelet-derived growth factor-B. Loss-of-function effects were also observed in
      HIF-1alpha-null embryonic stem cells. Depending on the cell type, expression of
      ANGPT1 and ANGPT2 was either activated or repressed in response to hypoxia or
      AdCA5. In all cases, there was complete concordance between the effects of
      hypoxia and AdCA5. Injection of AdCA5 into mouse eyes induced neovascularization
      in multiple capillary beds, including those not responsive to VEGF alone.
      Analysis of gene expression revealed increased expression of ANGPT1, ANGPT2,
      platelet-derived growth factor-B, placental growth factor, and VEGF mRNA in AdCA5
      injected eyes. These results indicate that HIF-1 functions as a master regulator
      of angiogenesis by controlling the expression of multiple angiogenic growth
      factors and that adenovirus-mediated expression of a constitutively active form
      of HIF-1alpha is sufficient to induce angiogenesis in nonischemic tissue of an
      adult animal.

PMID- 14576201
TI  - Novel polypyrimidine variation (IVS46: del T -39...-46) in ABCA1 causes exon
      skipping and contributes to HDL cholesterol deficiency in a family with premature
      coronary disease.
AB  - Recent studies have implicated mutations in the ATP-binding cassette transporter
      A1, ABCA1, as a cause of Tangier disease (TD) and familial
      hypoalphalipoproteinemia (FHA). We investigated a proband with very low levels of
      high-density lipoprotein cholesterol (HDL-C, 6 mg/dL) and a history of premature
      coronary heart disease (CHD). Sequencing of the ABCA1 gene revealed 2 distinct
      variants. The first mutation was a G5947A substitution (R1851Q). The second
      mutation was a single-nucleotide deletion of thymidine in a polypyrimidine tract
      located 33 to 46 bps upstream to the start of exon 47. This mutation does not
      involve the 3' acceptor splice site and is outside the lariat branchpoint
      sequence (IVS46: del T -39...-46). Amplification of cDNA obtained in cultured
      fibroblasts of the proband and affected family member revealed an abnormally
      spliced cDNA sequence with skipping of exon 47. These variants were not
      identified in over 400 chromosomes of healthy whites. Compound heterozygotes
      (n=4) exhibited the lowest HDL-C (11+/-5 mg/dL) and ApoA-I (35+/-15 mg/dL)
      compared with wild-type (n=25) (HDL-C 51+/-14 mg/dL; ApoA-I 133+/-21 mg/dL)
      (P<0.0005) or subjects affected with either R1851Q (n=6) (HDL-C 36+/-8; ApoA-I
      117+/-19) or IVS46: del T -39...-46 (n=5) (HDL-C 31+9; ApoA-I 115+28 (P<0.01).
      These data suggest that polypyrimidine tract variation may represent a novel
      mechanism for altered splicing and exon skipping that is independent of
      traditional intronic variants as previously identified in acceptor/donor splice
      regions or the lariat branchpoint domain.

PMID- 14576202
TI  - Transcriptional profiling of the heart reveals chamber-specific gene expression
      patterns.
AB  - Cardiac chamber-specific gene expression is critical for the normal development
      and function of the heart. To investigate the genetic basis of cardiac anatomical
      specialization, we have undertaken a nearly genome-wide transcriptional profiling
      of the four heart chambers and the interventricular septum. Rigorous statistical
      analysis has allowed the identification of known and novel members of gene
      families that are felt to be important in cardiac development and function,
      including LIM proteins, homeobox proteins, wnt and T-box pathway proteins, as
      well as structural proteins like actins and myosins. In addition, these studies
      have allowed the identification of thousands of additional differentially
      expressed genes, for which there is little structural or functional information.
      Clustering of genes with known and unknown functions provides insights into
      signaling pathways that are essential for development and maintenance of chamber
      specific features. To facilitate future research in this area, a searchable
      internet database has been constructed that allows study of the chamber-specific
      expression of any gene represented on this comprehensive microarray. It is
      anticipated that further study of genes identified through this effort will
      provide insights into the specialization of heart chamber tissues, and their
      specific roles in cardiac development, aging, and disease.

PMID- 14576204
TI  - Persistent neural activity: experiments and theory.

PMID- 14576203
TI  - Impaired acetylcholine-induced release of nitric oxide in the aorta of male
      aromatase-knockout mice: regulation of nitric oxide production by endogenous sex
      hormones in males.
AB  - The consequences of estrogen deficiency on the cardiovascular system have been
      widely examined in females. The effects of endogenous estrogen deficiency in
      males are less clear. The aromatase-knockout (ArKO) mouse lacks a functional
      Cyp19 gene, which encodes aromatase, and is thus incapable of synthesizing
      endogenous estrogen. In the present study, we examined the effect of lack of
      endogenous estrogens on vascular function in aortic rings isolated from male ArKO
      mice and compared these effects to rings from wild-type (WT) littermates. Full
      concentration-response curves to norepinephrine, acetylcholine, isoprenaline, and
      sodium nitroprusside were obtained in the absence and presence of the nitric
      oxide synthase inhibitor Nomega-nitro-L-arginine in aortic segments set up in
      isometric myographs. Responses to noradrenaline were not different in aorta from
      ArKO compared with WT mice. Both Nomega-nitro-L-arginine and endothelium
      denudation significantly shifted the noradrenaline concentration-response curve
      to the left; however, this shift was not different in ArKO compared with WT.
      Responses to the endothelium-dependent vasodilator acetylcholine were
      significantly blunted in aortic rings from ArKO mice (Emax, 58.2+/-0.9% and
      34.0+/-0.5% in wild-type and ArKO, respectively; P<0.05), whereas responses to
      the endothelium-independent agonist sodium nitroprusside and to the partial
      endothelium-dependent agonist isoprenaline were not affected. These findings
      suggest that endogenous estrogen facilitate vasorelaxation in males. This may be
      via modulating endothelial function rather than vascular smooth muscle cell
      responsiveness.

PMID- 14576205
TI  - Cortex, cognition and the cell: new insights into the pyramidal neuron and
      prefrontal function.
AB  - Arguably the most complex cortical functions are seated in human cognition, the
      how and why of which have been debated for centuries by theologians, philosophers
      and scientists alike. In his best-selling book, An Astonishing Hypothesis: A
      Scientific Search for the Soul, Francis Crick refined the view that these
      qualities are determined solely by cortical cells and circuitry. Put simply,
      cognition is nothing more, or less, than a biological function. Accepting this to
      be the case, it should be possible to identify the mechanisms that subserve
      cognitive processing. Since the pioneering studies of Lorent de No and Hebb, and
      the more recent studies of Fuster, Miller and Goldman-Rakic, to mention but a
      few, much attention has been focused on the role of persistent neural activity in
      cognitive processes. Application of modern technologies and modelling techniques
      has led to new hypotheses about the mechanisms of persistent activity. Here I
      focus on how regional variations in the pyramidal cell phenotype may determine
      the complexity of cortical circuitry and, in turn, influence neural activity.
      Data obtained from thousands of individually injected pyramidal cells in sensory,
      motor, association and executive cortex reveal marked differences in the numbers
      of putative excitatory inputs received by these cells. Pyramidal cells in
      prefrontal cortex have, on average, up to 23 times more dendritic spines than
      those in the primary visual area. I propose that without these specializations in
      the structure of pyramidal cells, and the circuits they form, human cognitive
      processing would not have evolved to its present state. I also present data from
      both New World and Old World monkeys that show varying degrees of complexity in
      the pyramidal cell phenotype in their prefrontal cortices, suggesting that
      cortical circuitry and, thus, cognitive styles are evolving independently in
      different species.

PMID- 14576206
TI  - Selective delay activity in the cortex: phenomena and interpretation.
AB  - The present article does not intend to present technical progress nor recent
      successes in accounting for experiments, as this issue of the journal presents a
      rich inventory. Rather, the paper presents a retrospective reflection on the
      history of the subject; on the relation between the different aspects of the
      concepts and the phenomena involved; on its strengths and weaknesses; and on some
      future prospects. It is a tribute to an extremely rich and growing wealth of
      physiological phenomena and of interpretative concepts. Yet the extent of
      achievement is used to expose open questions, which appear to become ever deeper.
      It is also an attempt to make the subject a matter of discourse between
      biologists and modelers, without the distraction of technical details.

PMID- 14576207
TI  - Dynamics and plasticity of stimulus-selective persistent activity in cortical
      network models.
AB  - Persistent neuronal activity is widespread in many areas of the cerebral cortex
      of monkeys performing cognitive tasks with a working memory component. Modeling
      studies have helped understanding of the conditions under which persistent
      activity can be sustained in cortical circuits. Here, we first review several
      basic models of persistent activity, including bistable models with excitation
      only and multistable models for working memory of a discrete set of pictures or
      objects with structured excitation and global inhibition. In many experiments,
      persistent activity has been shown to be subject to changes due to associative
      learning. In cortical network models, Hebbian learning shapes the synaptic
      structure and, in turn, the properties of persistent activity when pictures are
      associated together in the course of a task. It is shown how the theoretical
      models can reproduce basic experimental findings of neurophysiological recordings
      from inferior temporal and perirhinal cortices obtained using the following
      experimental protocols: (i) the pair-associate task; (ii) the pair-associate task
      with color switch; and (iii) the delay match to sample task with a fixed sequence
      of samples.

PMID- 14576208
TI  - Persistent neural activity in head direction cells.
AB  - Many neurons throughout the rat limbic system discharge in relation to the
      animal's directional heading with respect to its environment. These so-called
      head direction (HD) cells exhibit characteristics of persistent neural activity.
      This article summarizes where HD cells are found, their major properties, and
      some of the important experiments that have been conducted to elucidate how this
      signal is generated. The number of HD and angular head velocity cells was
      estimated for several brain areas involved in the generation of the HD signal,
      including the postsubiculum, anterior dorsal thalamus, lateral mammillary nuclei
      and dorsal tegmental nucleus. The HD cell signal has many features in common with
      what is known about how neural integration is accomplished in the oculomotor
      system. The nature of the HD cell signal makes it an attractive candidate for
      using neural network models to elucidate the signal's underlying mechanisms. The
      conditions that any network model must satisfy in order to accurately represent
      how the nervous system generates this signal are highlighted and areas where key
      information is missing are discussed.

PMID- 14576209
TI  - History dependence of rate covariation between neurons during persistent activity
      in an oculomotor integrator.
AB  - Persistent firing in response to a brief stimulus is a neural correlate of short
      term memory in a variety of systems. In the oculomotor neural integrator,
      persistent firing that encodes eye position is maintained in response to
      transient saccadic eye-velocity commands. To a first approximation, firing rates
      in the integrator vary linearly with eye position. Thus, viewed across many
      cells, the pattern of persistent firing in the integrator may be constrained to a
      unique line of stable states. Here this idea was tested by examining the
      relationship between firing rates of simultaneously recorded neurons. Paired
      recordings were obtained in awake goldfish from neurons in hindbrain area I, an
      essential part of the horizontal eye-position integrator. During spontaneous eye
      movements consisting of sequential fixations at different horizontal positions,
      the pair relationship between the majority of cells on the same side of the
      integrator was not unique: for a given rate of one cell, the rate of the paired
      cell assumed different values that depended systematically on the preceding
      saccade history. This finding suggests that the set of persistent firing states
      that encode eye position is not constrained to a unique line, and that models
      with stable states restricted to a such a line need to be modified accordingly.

PMID- 14576210
TI  - Robust persistent neural activity in a model integrator with multiple hysteretic
      dendrites per neuron.
AB  - Short-term memory is often correlated with persistent changes in neuronal firing
      rates in response to transient inputs. We model the persistent maintenance of an
      analog eye position signal by an oculomotor neural integrator receiving transient
      eye movement commands. Previous models of this network rely on precisely tuned
      positive feedback with <1% tolerance to mistuning, or use neurons that exhibit
      large discontinuities in firing rate with small changes in eye position. We show
      analytically how using neurons with multiple bistable dendritic compartments can
      enhance the robustness of eye fixations to mistuning while reproducing the
      approximately linear and continuous relationship between neuronal firing rates
      and eye position, and the dependence of neuron pair firing rate relationships on
      the direction of the previous saccade. The response of the model to continuously
      varying inputs makes testable predictions for the performance of the
      vestibuloocular reflex. Our results suggest that dendritic bistability could
      stabilize the persistent neural activity observed in working memory systems.

PMID- 14576211
TI  - Timing and neural encoding of somatosensory parametric working memory in macaque
      prefrontal cortex.
AB  - We trained monkeys to compare the frequencies of two mechanical vibrations
      applied sequentially to the tip of a finger and to report which of the two
      stimuli had the higher frequency. This task requires remembering the first
      frequency during the delay period between the two stimuli. Recordings were made
      from neurons in the inferior convexity of the prefrontal cortex (PFC) while the
      monkeys performed the task. We report neurons that fire persistently during the
      delay period, with a firing rate that is a monotonic function of the frequency of
      the first stimulus. Separately from, and in addition to, their correlation with
      the first stimulus, the delay period firing rates of these neurons were
      correlated with the behavior of the monkey, in a manner consistent with their
      interpretation as the neural substrate of working memory during the task. Most
      neurons had firing rates that varied systematically with time during the delay
      period. We suggest that this time-dependent activity may encode time itself and
      may be an intrinsic part of active memory maintenance mechanisms.

PMID- 14576213
TI  - Persistent cortical activity: mechanisms of generation and effects on neuronal
      excitability.
AB  - Local cortical networks in the prefrontal cortex and visual cortex are capable of
      spontaneously generating sustained activity for periods of seconds or longer.
      This sustained activity is generated through recurrent excitation between
      pyramidal cells that is controlled by feedback inhibition and can have both a
      rapid onset and a rapid offset. The period of activity is associated with a
      marked increase in neuronal responsiveness to the intracellular injection of
      current pulses, especially those of smaller amplitude. Independently mimicking
      the depolarization, increase in membrane conductance and increase in noise
      associated with sustained activity revealed that the depolarization is largely
      responsible for the increase in neuronal responsiveness, although an increase in
      membrane noise also facilitates responses to small inputs. These results indicate
      that the persistent activity associated with the performance of working memory
      tasks may be generated largely through recurrent networks. They also suggest that
      feedback pathways, such as those involved in selective attention, may exert a
      powerful influence on neuronal responsiveness through synaptic bombardment.

PMID- 14576212
TI  - A recurrent network model of somatosensory parametric working memory in the
      prefrontal cortex.
AB  - A parametric working memory network stores the information of an analog stimulus
      in the form of persistent neural activity that is monotonically tuned to the
      stimulus. The family of persistent firing patterns with a continuous range of
      firing rates must all be realizable under exactly the same external conditions
      (during the delay when the transient stimulus is withdrawn). How this can be
      accomplished by neural mechanisms remains an unresolved question. Here we present
      a recurrent cortical network model of irregularly spiking neurons that was
      designed to simulate a somatosensory working memory experiment with behaving
      monkeys. Our model reproduces the observed positively and negatively monotonic
      persistent activity, and heterogeneous tuning curves of memory activity. We show
      that fine-tuning mathematically corresponds to a precise alignment of cusps in
      the bifurcation diagram of the network. Moreover, we show that the fine-tuned
      network can integrate stimulus inputs over several seconds. Assuming that such
      time integration occurs in neural populations downstream from a tonically
      persistent neural population, our model is able to account for the slow ramping
      up and ramping-down behaviors of neurons observed in prefrontal cortex.

PMID- 14576214
TI  - Regulation of persistent activity by background inhibition in an in vitro model
      of a cortical microcircuit.
AB  - We combined in vitro intracellular recording from prefrontal cortical neurons
      with simulated synaptic activity of a layer 5 prefrontal microcircuit using a
      dynamic clamp. During simulated in vivo background conditions, the cell responded
      to a brief depolarization with a sequence of spikes that outlasted the
      depolarization, mimicking the activity of a cell recorded during the delay period
      of a working memory task in the behaving monkey. The onset of sustained activity
      depended on the number of action potentials elicited by the cue-like
      depolarization. Too few spikes failed to provide enough NMDA drive to elicit
      sustained reverberations; too many spikes activated a slow intrinsic
      hyperpolarization current that prevented spiking; an intermediate number of
      spikes produced sustained activity. When high dopamine levels were simulated by
      depolarizing the cell and by increasing the amount of NMDA current, the cell
      exhibited spontaneous 'up-states' that terminated by the activation of a slow
      intrinsic hyperpolarizing current. The firing rate during the delay period could
      be effectively modulated by the standard deviation of the inhibitory background
      synaptic noise without significant changes in the background firing rate before
      cue onset. These results suggest that the balance between fast feedback
      inhibition and slower AMPA and NMDA feedback excitation is critical in initiating
      persistent activity and that the maintenance of persistent activity may be
      regulated by the amount of correlated background inhibition.

PMID- 14576215
TI  - Synaptic basis of persistent activity in prefrontal cortex in vivo and in
      organotypic cultures.
AB  - Persistent activity is observed in many cortical and subcortical brain regions,
      and may subserve a variety of functions. Within the prefrontal cortex (PFC),
      neurons transiently maintain information in working memory via persistent
      activity patterns; however, the mechanisms involved are largely unknown. The
      present study used intracellular recordings from deep layer PFC neurons in vivo
      and patch-clamp recordings from PFC neurons in organotypic brain slice cultures
      to examine the ionic mechanisms underlying persistent activity states evoked by
      various inputs. Persistent activity had consistent features regardless of the
      initiating stimulus; it was driven by non-NMDA glutamate receptors yet consisted
      of an initial GABA mediated component, followed by a prolonged synaptically
      mediated inward current that maintained the sustained depolarization on which
      rode many asynchronous GABA-mediated events. The stereotyped nature of the
      multiple-component persistent activity pattern reported here might be a common
      feature of interconnected cortical networks but within PFC could be related to
      the persistent activity required for working memory.

PMID- 14576216
TI  - Dopaminergic modulation of long-term synaptic plasticity in rat prefrontal
      neurons.
AB  - In rat prefrontal cortex (the prelimbic area of medial frontal cortex), the
      induction of long-term depression (LTD) and long-term potentiation (LTP) of
      glutamatergic synapses is powerfully modulated by dopamine. The presence of
      dopamine in the bathing medium facilitates LTD in slice preparations, whereas in
      the anesthetized intact brain, dopamine released from dopaminergic axon terminals
      in the prefrontal cortex facilitates LTP. Dopaminergic facilitation of LTD is at
      least partly achieved by postsynaptic biochemical mechanisms in which enzymatic
      processes triggered by dopamine receptor activation cooperate with those
      triggered by glutamate metabotropic receptor activation. Evidence suggests that
      dopamine facilitates LTP also in the slice condition. In this case, dopamine
      receptors must be pre-stimulated ('primed') before the application of high
      frequency stimuli in the presence of dopamine. This procedure may mimic baseline
      stimulation of dopamine receptors that occurs under physiological conditions.

PMID- 14576217
TI  - A role for neural integrators in perceptual decision making.
AB  - Decisions based on uncertain information may benefit from an accumulation of
      information over time. We asked whether such an accumulation process may underlie
      decisions about the direction of motion in a random dot kinetogram. To address
      this question we developed a computational model of the decision process using
      ensembles of neurons whose spiking activity mimics neurons recorded in the
      extrastriate visual cortex (area MT or V5) and a sensorimotor association area of
      the parietal lobe (area LIP). The model instantiates the hypothesis that neurons
      in sensorimotor association areas compute the time integral of sensory signals
      from the visual cortex, construed as evidence for or against a proposition, and
      that the decision is made when the integrated evidence reaches a threshold. The
      model explains a variety of behavioral and physiological measurements obtained
      from monkeys.

PMID- 14576218
TI  - Health needs of women who have sex with women.

PMID- 14576219
TI  - Britain prefers talk to action.

PMID- 14576220
TI  - Why a special issue of the BMJ on South Asia?

PMID- 14576221
TI  - Topical corticosteroids in atopic dermatitis.

PMID- 14576222
TI  - The rise of trust doctors.

PMID- 14576223
TI  - Belgium to subsidise costs of contraception to teenagers.

PMID- 14576226
TI  - Competition body rules that drug companies "abused" their position.

PMID- 14576227
TI  - Silicone breast implants still available in UK.

PMID- 14576228
TI  - Journal apologises for publishing author's work without permission.

PMID- 14576229
TI  - Safety concerns about breast implants persist.

PMID- 14576231
TI  - NHS cervical screening programme to introduce liquid based cytology.

PMID- 14576232
TI  - Tobacco companies start price war in Poland to offset tax rises.

PMID- 14576233
TI  - Charities say southern Sudan faces a health crisis and record malnutrition.

PMID- 14576234
TI  - Smallpox bioterrorist conference highlights divisions over vaccines.

PMID- 14576235
TI  - Regulatory body is ordered to inquire into doctor's decision to test patient for
      HIV without permission.

PMID- 14576236
TI  - Governor Jeb Bush intervenes in "right to die" case.

PMID- 14576238
TI  - The virus hunter.

PMID- 14576240
TI  - Nigerian immunisation programme accused of distributing expired vaccines.

PMID- 14576241
TI  - WHO inquiry into SARS leaves questions unanswered.

PMID- 14576242
TI  - Disabled mother whose sterilisation failed cannot claim the extra costs of
      bringing up a child.

PMID- 14576243
TI  - Man convicted of grievous bodily harm for infecting two women with HIV.

PMID- 14576244
TI  - Drug company and pharmacy send unsolicited samples of Prozac to Florida
      residents.

PMID- 14576245
TI  - Metformin in polycystic ovary syndrome: systematic review and meta-analysis.
AB  - OBJECTIVE: To assess the effectiveness of metformin in improving clinical and
      biochemical features of polycystic ovary syndrome. DESIGN: Systematic review and
      meta-analysis. DATA SOURCES: Randomised controlled trials that investigated the
      effect of metformin compared with either placebo or no treatment, or compared
      with an ovulation induction agent. SELECTION OF STUDIES: 13 trials were included
      for analysis, including 543 women with polycystic ovary syndrome that was defined
      by using biochemical or ultrasound evidence. MAIN OUTCOME MEASURE: Pregnancy and
      ovulation rates. Secondary outcomes of clinical and biochemical features of
      polycystic ovary syndrome. RESULTS: Meta-analysis showed that metformin is
      effective in achieving ovulation in women with polycystic ovary syndrome, with
      odds ratios of 3.88 (95% confidence interval 2.25 to 6.69) for metformin compared
      with placebo and 4.41 (2.37 to 8.22) for metformin and clomifene compared with
      clomifene alone. An analysis of pregnancy rates shows a significant treatment
      effect for metformin and clomifene (odds ratio 4.40, 1.96 to 9.85). Metformin has
      an effect in reducing fasting insulin concentrations, blood pressure, and low
      density lipoprotein cholesterol. We found no evidence of any effect on body mass
      index or waist:hip ratio. Metformin was associated with a higher incidence of
      nausea, vomiting, and other gastrointestinal disturbance. CONCLUSIONS: Metformin
      is an effective treatment for anovulation in women with polycystic ovary
      syndrome. Its choice as a first line agent seems justified, and there is some
      evidence of benefit on variables of the metabolic syndrome. No data are available
      regarding the safety of metformin in long term use in young women and only
      limited data on its safety in early pregnancy. It should be used as an adjuvant
      to general lifestyle improvements and not as a replacement for increased exercise
      and improved diet.

PMID- 14576247
TI  - Recruitment of doctors to non-standard grades in the NHS: analysis of job
      advertisements and survey of advertisers.
AB  - OBJECTIVES: To estimate the proportion of advertised non-consultant hospital
      posts that do not conform to nationally recognised terms and conditions of
      service and to investigate why these posts exist, who fills them, and what the
      doctors in such jobs do. DESIGN: Analysis of job advertisements and a cross
      sectional survey of advertisers. SETTING: Job advertisements in one of the
      leading UK publications listing hospital doctor vacancies (BMJ Careers). RESULTS:
      Nearly a quarter of non-consultant posts advertised in the two study periods (23%
      and 21%) were for non-standard grade posts. A questionnaire was sent to the
      medical staffing officer for each post. Of 430 questionnaires sent out 192 (45%)
      were returned. 98 trusts said they advertised non-standard grades because there
      was no more funding from the deanery for approved posts and 75 because service
      needs could not be met by doctors in training grades. In 132 posts (69%) the post
      holder would be required to do on-call work, and 50 advertisers (26%) required on
      call duty for 1 in 5 or more frequently, which would conflict with the European
      Working Time Directive. 131 advertisers (68%) expected the posts to be filled by
      doctors from outside the European Economic Area. CONCLUSIONS: Non-standard grade
      posts are mostly being created to meet service requirements when there is no more
      funding for standard training posts and are expected to be filled by doctors from
      overseas. Doctors in such posts can be more easily exploited and their careers
      hindered. The Department of Health's annual census should include non-standard
      grade doctors.

PMID- 14576246
TI  - Hydralazine for treatment of severe hypertension in pregnancy: meta-analysis.
AB  - OBJECTIVE: To review outcomes in randomised controlled trials comparing
      hydralazine against other antihypertensives for severe hypertension in pregnancy.
      STUDY DESIGN: Meta-analysis of randomised controlled trials (published between
      1966 and September 2002) of short acting antihypertensives for severe
      hypertension in pregnancy. Independent data abstraction by two reviewers. Data
      were entered into RevMan software for analysis (fixed effects model, relative
      risk and 95% confidence interval); in a secondary analysis, risk difference was
      also calculated. RESULTS: Of 21 trials (893 women), eight compared hydralazine
      with nifedipine and five with labetalol. Hydralazine was associated with a trend
      towards less persistent severe hypertension than labetalol (relative risk 0.29
      (95% confidence interval 0.08 to 1.04); two trials), but more severe hypertension
      than nifedipine or isradipine (1.41 (0.95 to 2.09); four trials); there was
      significant heterogeneity in outcome between trials and differences in
      methodological quality. Hydralazine was associated with more maternal hypotension
      (3.29 (1.50 to 7.23); 13 trials); more caesarean sections (1.30 (1.08 to 1.59);
      14 trials); more placental abruption (4.17 (1.19 to 14.28); five trials); more
      maternal oliguria (4.00 (1.22 to 12.50); three trials); more adverse effects on
      fetal heart rate (2.04 (1.32 to 3.16); 12 trials); and more low Apgar scores at
      one minute (2.70 (1.27 to 5.88); three trials). For all but Apgar scores,
      analysis by risk difference showed heterogeneity between trials. Hydralazine was
      associated with more maternal side effects (1.50 (1.16 to 1.94); 12 trials) and
      with less neonatal bradycardia than labetalol (risk difference -0.24 (-0.42 to 
      0.06); three trials). CONCLUSIONS: The results are not robust enough to guide
      clinical practice, but they do not support use of hydralazine as first line for
      treatment of severe hypertension in pregnancy. Adequately powered clinical trials
      are needed, with a comparison of labetalol and nifedipine showing the most
      promise.

PMID- 14576248
TI  - Russian mortality trends for 1991-2001: analysis by cause and region.
AB  - OBJECTIVES: To investigate trends in Russian mortality for 1991-2001 with
      particular reference to trends since the Russian economic crisis in 1998 and to
      geographical differences within Russia. DESIGN: Analysis of data obtained from
      the Russian State statistics committee for 1991-2001. All cause mortality was
      compared between seven federal regions. Comparison of cause specific rates was
      conducted for young (15-34 years) and middle aged adults (35-69 years). The
      number of Russian adults who died before age 70 in the period 1992-2001 and whose
      deaths were attributable to increased mortality was calculated. MAIN OUTCOME
      MEASURES: Age, sex, and cause specific mortality standardised to the world
      population. RESULTS: Mortality increased substantially after the economic crisis
      in 1998, with life expectancy falling to 58.9 years among men and 71.8 years
      among women by 2001. Most of these fluctuations were due to changes in mortality
      from vascular disease and violent deaths (mainly suicides, homicides,
      unintentional poisoning, and traffic incidents) among young and middle aged
      adults. Trends were similar in all parts of Russia. An extra 2.5-3 million
      Russian adults died in middle age in the period 1992-2001 than would have been
      expected based on 1991 mortality. CONCLUSIONS: Russian mortality was already high
      in 1991 and has increased further in the subsequent decade. Fluctuations in
      mortality seem to correlate strongly with underlying economic and societal
      factors. On an individual level, alcohol consumption is strongly implicated in
      being at least partially responsible for many of these trends.

PMID- 14576249
TI  - Whispered voice test for screening for hearing impairment in adults and children:
      systematic review.
AB  - OBJECTIVE: To determine the accuracy of the whispered voice test in detecting
      hearing impairment in adults and children. DESIGN: Systematic review of studies
      of test accuracy. DATA SOURCES: Medline, Embase, Science Citation Index,
      unpublished theses, manual searching of bibliographies of known primary and
      review articles, and contact with authors. STUDY SELECTION: Two reviewers
      independently selected and extracted data on study characteristics, quality, and
      accuracy of studies. Studies were included if they had cross sectional designs,
      at least one of the index tests was the whispered voice test, and the reference
      test (audiometry) was performed on at least 80% of the participants. DATA
      EXTRACTION: Data were used to form 2x2 contingency tables with hearing impairment
      by audiometry as the reference standard. DATA SYNTHESIS: The eight studies that
      were found used six different techniques. The sensitivity in the four adult
      studies was 90% or 100% and the specificity was 70% to 87%. The sensitivity in
      the four childhood studies ranged from 80% to 96% and specificity ranged from 90%
      to 98%. CONCLUSION: The whispered voice test is a simple and accurate test for
      detecting hearing impairment. There is some concern regarding the lower
      sensitivity in children and the overall reproducibility of the test, particularly
      in primary care settings. Further studies should be conducted in primary care
      settings to explore the influence of components of the testing procedure to
      optimise test sensitivity and to promote standardisation of the testing
      procedure.

PMID- 14576250
TI  - Evaluation of extended training for general practice in Northern Ireland:
      qualitative study.
AB  - OBJECTIVE: To evaluate participants' perceptions of the impact on them of an
      additional six months' training beyond the standard 12 month general practice
      vocational training scheme. DESIGN: Qualitative study using focus groups.
      SETTING: General practice vocational training in Northern Ireland. PARTICIPANTS:
      13 general practitioner registrars, six of whom participated in the additional
      six months' training, and four trainers involved in the additional six months'
      training. MAIN OUTCOME MEASURES: : Participants' views about their experiences in
      18 month and 12 month courses. RESULTS: Participants reported that the 12 month
      course was generally positive but was too pressurised and focused on
      examinations, and also that it had a negative impact on self care. The nature of
      the learning and assessment was reported to have left participants feeling averse
      to further continuing education and lacking in confidence. In contrast, the
      extended six month component was reported to have restimulated learning by
      focusing more on patient care and promoting self directed learning. It developed
      confidence, promoted teamwork, and gave experience of two practice contexts, and
      was reported as valuable by both ex-registrars and trainers. However, both the 12
      and 18 month courses left participants feeling underprepared for practice
      management and self care. CONCLUSIONS: 12 months' training in general practice
      does not provide doctors with the necessary competencies and confidence to enter
      independent practice. The extended period was reported to promote greater
      professional development, critical evaluation skills, and orientation to lifelong
      learning but does not fill all the gaps.

PMID- 14576251
TI  - Disseminated intravascular coagulation: old disease, new hope.

PMID- 14576252
TI  - Assisted conception and the law in the United Kingdom.

PMID- 14576253
TI  - NHS and the Health and Social Care Bill: end of Bevan's vision?

PMID- 14576254
TI  - "Failed back surgery syndrome".

PMID- 14576255
TI  - Label is unhelpful.

PMID- 14576256
TI  - Health of indigenous people: health of Aboriginal communities can be improved by
      innovative methods.

PMID- 14576257
TI  - Health of indigenous people: local practices and practitioners can become part of
      comprehensive programme.

PMID- 14576258
TI  - Health of indigenous people: use of health services by indigenous population can
      be improved.

PMID- 14576259
TI  - Health of indigenous people: traditional medicine is being practised
      successfully.

PMID- 14576260
TI  - Feasibility of opportunistic disease prevention: personal and public health are
      at stake.

PMID- 14576261
TI  - More transparency in reviewing is called for.

PMID- 14576262
TI  - Feasibility of opportunistic disease prevention: doctors' responsibilities should
      not be reduced.

PMID- 14576263
TI  - Task imposed on prisons is impossible.

PMID- 14576264
TI  - Longevity and C282Y mutation for haemochromatosis: survival of C282Y homozygotes
      does not preclude screening for HFE mutations.

PMID- 14576265
TI  - Longevity and C282Y mutation for haemochromatosis: data do not support
      conclusion.

PMID- 14576266
TI  - More on copying letters to patients: audiotapes can be helpful in outpatient
      clinics.

PMID- 14576267
TI  - More on copying letters to patients: use of letters in the consulting process
      still seems Victorian.

PMID- 14576269
TI  - In praise of medical secretaries: pay and conditions should reflect crucial role
      of medical secretaries in clinical teams.

PMID- 14576270
TI  - Non-standard grade (trust grade) doctors: the human resources view.

PMID- 14576271
TI  - Non-standard grade (trust grade) doctors: the BMA seniors' view.

PMID- 14576272
TI  - Non-standard grade (trust grade) doctors: the BMA juniors' view.

PMID- 14576273
TI  - Non-standard grade (trust grade) doctors: the Department of Health's view.

PMID- 14576274
TI  - Non-standard grade (trust grade) doctors: a postgraduate dean's view.

PMID- 14576276
TI  - Convergent neofunctionalization by positive Darwinian selection after ancient
      recurrent duplications of the xanthine dehydrogenase gene.
AB  - Gene duplication is a primary source of molecular substrate for the emergence of
      evolutionary novelties. The chances for redundant gene sequences to evolve new
      functions are small compared with the probability that the copies become disabled
      by deleterious mutations. Functional divergence after gene duplication can result
      in two alternative evolutionary fates: one copy acquires a novel function
      (neofunctionalization), or each copy adopts part of the tasks of their parental
      gene (subfunctionalization). The relative prevalence of each outcome is unknown.
      Similarly unknown is the relative importance of positive selection versus random
      fixation of neutral mutations. Aldehyde oxidase (Ao) and xanthine dehydrogenase
      (Xdh) genes encode two complex members of the xanthine oxidase family of molybdo
      flavoenzymes that carry different functions. Ao is known to have originated from
      a duplicate of an Xdh gene in eukaryotes, before the origin of multicellularity.
      We show that (i) Ao evolved independently twice from two different Xdh paralogs,
      the second time in the chordates, before the diversification of vertebrates; (ii)
      after each duplication, the Ao duplicate underwent a period of rapid evolution
      during which identical sites across the two molecules, involving the flavin
      adenine dinucleotide and substrate-binding pockets, were subjected to intense
      positive Darwinian selection; and (iii) the second Ao gene likely endured two
      periods of redundancy, initially as a duplicate of Xdh and later as a functional
      equivalent of the old Ao, which is currently absent from the vertebrate genome.
      Caution is appropriate in structural genomics when using sequence similarity for
      assigning protein function.

PMID- 14576277
TI  - Contribution of climate-driven change in continental water storage to recent sea
      level rise.
AB  - Using a global model of continental water balance, forced by interannual
      variations in precipitation and near-surface atmospheric temperature for the
      period 1981-1998, we estimate the sea-level changes associated with climate
      driven changes in storage of water as snowpack, soil water, and ground water;
      storage in ice sheets and large lakes is not considered. The 1981-1998 trend is
      estimated to be 0.12 mm/yr, and substantial interannual fluctuations are
      inferred; for 1993-1998, the trend is 0.25 mm/yr. At the decadal time scale, the
      terrestrial contribution to eustatic (i.e., induced by mass exchange) sea-level
      rise is significantly smaller than the estimated steric (i.e., induced by density
      changes) trend for the same period, but is not negligibly small. In the model the
      sea-level rise is driven mainly by a downtrend in continental precipitation
      during the study period, which we believe was generated by natural variability in
      the climate system.

PMID- 14576278
TI  - The proteome of Saccharomyces cerevisiae mitochondria.
AB  - We performed a comprehensive approach to determine the proteome of Saccharomyces
      cerevisiae mitochondria. The proteins of highly pure yeast mitochondria were
      separated by several independent methods and analyzed by tandem MS. From >20
      million MS spectra, 750 different proteins were identified, indicating an
      involvement of mitochondria in numerous cellular processes. All known components
      of the oxidative phosphorylation machinery, the tricarboxylic acid cycle, and the
      stable mitochondria-encoded proteins were found. Based on the mitochondrial
      proteins described in the literature so far, we calculate that the identified
      proteins represent approximately 90% of all mitochondrial proteins. The function
      of a quarter of the identified proteins is unknown. The mitochondrial proteome
      will provide an important database for the analysis of new mitochondrial and
      mitochondria-associated functions and the characterization of mitochondrial
      diseases.

PMID- 14576279
TI  - Evidence that the bypassing ribosome travels through the coding gap.
AB  - In translational bypassing, a peptidyl-tRNA::ribosome complex skips over a number
      of nucleotides in a messenger sequence and resumes protein chain elongation after
      a "landing site" downstream of the bypassed region. The present experiments
      demonstrate that the complex "scans" processively through the bypassed region.
      This conclusion rests on three observations. (i) When two potential "landing
      sites" are present, the protein sequence of the product shows that virtually all
      ribosomes land at the first and virtually none at the second. (ii) In such a
      sequence with two landing sites, the presence of a terminator triplet in phase in
      the coding region immediately after the first landing site drastically reduces
      the efficiency of bypassing. (iii) Internally complementary sequences that can
      form a stable stemloop in the bypassed region significantly reduce the efficiency
      of bypassing. We analyze bypassing from a given "takeoff" site to "landing sites"
      at different distances downstream so as to derive estimates of the frequency of
      ribosome takeoff and of the stability of the bypassing complex.

PMID- 14576280
TI  - Engineering of a water-soluble plant cytochrome P450, CYP73A1, and NMR-based
      orientation of natural and alternate substrates in the active site.
AB  - CYP73A1 catalyzes cinnamic acid hydroxylation, a reaction essential for the
      synthesis of lignin monomers and most phenolic compounds in higher plants. The
      native CYP73A1, initially isolated from Jerusalem artichoke (Helianthus
      tuberosus), was engineered to simplify purification from recombinant yeast and
      improve solublity and stability in the absence of detergent by replacing the
      hydrophobic N terminus with the peptitergent amphipathic sequence PD1. Optimized
      expression and purification procedures yielded 4 mg engineered CYP73A1 L(-1)
      yeast culture. This water-soluble enzyme was suitable for 1H-nuclear magnetic
      resonance (NMR) investigation of substrate positioning in the active site. The
      metabolism and interaction with the enzyme of cinnamate and four analogs were
      compared by UV-visible and 1H-NMR analysis. It was shown that trans-3
      thienylacrylic acid, trans-2-thienylacrylic acid, and 4-vinylbenzoic acid are
      good ligands and substrates, whereas trans-4-fluorocinnamate is a competitive
      inhibitor. Paramagnetic relaxation effects of CYP73A1-Fe(III) on the 1H-NMR
      spectra of cinnamate and analogs indicate that their average initial orientation
      in the active site is parallel to the heme. Initial orientation and distances of
      ring protons to the iron do not explain the selective hydroxylation of cinnamate
      in the 4-position or the formation of single products from the thienyl compounds.
      Position adjustments are thus likely to occur during the later steps of the
      catalytic cycle.

PMID- 14576281
TI  - Synthesis of the Arabidopsis bifunctional lysine-ketoglutarate
      reductase/saccharopine dehydrogenase enzyme of lysine catabolism is concertedly
      regulated by metabolic and stress-associated signals.
AB  - In plants, excess cellular lysine (Lys) is catabolized into glutamic acid and
      acetyl-coenzyme A; yet, it is still not clear whether this pathway has other
      functions in addition to balancing Lys levels. To address this issue, we examined
      the effects of stress-related hormones, abscisic acid (ABA), and jasmonate, as
      well as various metabolic signals on the production of the mRNA and polypeptide
      of the bifunctional Lys-ketoglutarate reductase (LKR)/saccharopine dehydrogenase
      (SDH) enzyme, which contains the first two linked enzymes of Lys catabolism. The
      level of LKR/SDH was strongly enhanced by ABA, jasmonate, and sugar starvation,
      whereas excess sugars and nitrogen starvation reduced its level; thus this
      pathway appears to fulfill multiple functions in stress-related and
      carbon/nitrogen metabolism. Treatments with combination of hormones and/or
      metabolites, as well as use of ABA mutants in conjunction with the tester sugars
      mannose and 3-O-methyl-glucose further supported the idea that the hormonal and
      metabolic signals apparently operate through different signal transduction
      cascades. The stimulation of LKR/SDH protein expression by ABA is regulated by a
      signal transduction cascade that contains the ABI1-1 and ABI2-1 protein
      phosphatases. By contrast, the stimulation of LKR/SDH protein expression by sugar
      starvation is regulated by the hexokinase-signaling cascade in a similar manner
      to the repression of many photosynthetic genes by sugars. These findings suggest
      a metabolic and mechanistic link between Lys catabolism and photosynthesis
      related metabolism in the regulation of carbon/nitrogen partitioning.

PMID- 14576283
TI  - Urea transport by nitrogen-regulated tonoplast intrinsic proteins in Arabidopsis.
AB  - Urea is the major nitrogen (N) form supplied as fertilizer in agricultural plant
      production and also an important N metabolite in plants. Because urea transport
      in plants is not well understood, the aim of the present study was to isolate
      urea transporter genes from the model plant Arabidopsis. Using heterologous
      complementation of a urea uptake-defective yeast (Saccharomyces cerevisiae)
      mutant allowed to isolate AtTIP1;1, AtTIP1;2, AtTIP2;1, and AtTIP4;1 from a cDNA
      library of Arabidopsis. These cDNAs encode channel-like tonoplast intrinsic
      proteins (TIPs) that belong to the superfamily of major intrinsic proteins (or
      aquaporins). All four genes conferred growth of a urea uptake-defective yeast
      mutant on 2 mm urea in a phloretin-sensitive and pH-independent manner. Uptake
      studies using 14C-labeled urea into AtTIP2;1-expressing Xenopus laevis oocytes
      demonstrated that AtTIP2;1 facilitated urea transport also in a pH-independent
      manner and with linear concentration dependency. Expression studies showed that
      AtTIP1;2, AtTIP2;1, and AtTIP4;1 genes were up-regulated during early germination
      and under N deficiency in roots but constitutively expressed in shoots.
      Subcellular localization of green fluorescent protein-fused AtTIPs indicated that
      AtTIP1;2, AtTIP2;1, and AtTIP4;1 were targeted mainly to the tonoplast and other
      endomembranes. Thus, in addition to their role as water channels, TIP
      transporters may play a role in equilibrating urea concentrations between
      different cellular compartments.

PMID- 14576282
TI  - The maize Single myb histone 1 gene, Smh1, belongs to a novel gene family and
      encodes a protein that binds telomere DNA repeats in vitro.
AB  - We screened maize (Zea mays) cDNAs for sequences similar to the single myb-like
      DNA-binding domain of known telomeric complex proteins. We identified, cloned,
      and sequenced five full-length cDNAs representing a novel gene family, and we
      describe the analysis of one of them, the gene Single myb histone 1 (Smh1). The
      Smh1 gene encodes a small, basic protein with a unique triple motif structure of
      (a) an N-terminal SANT/myb-like domain of the homeodomain-like superfamily of 3
      helical-bundle-fold proteins, (b) a central region with homology to the conserved
      H1 globular domain found in the linker histones H1/H5, and (c) a coiled-coil
      domain near the C terminus. The Smh-type genes are plant specific and include a
      gene family in Arabidopsis and the PcMYB1 gene of parsley (Petroselinum crispum)
      but are distinct from those (AtTRP1, AtTBP1, and OsRTBP1) recently shown to
      encode in vitro telomere-repeat DNA-binding activity. The Smh1 gene is expressed
      in leaf tissue and maps to chromosome 8 (bin 8.05), with a duplicate locus on
      chromosome 3 (bin 3.09). A recombinant full-length SMH1, rSMH1, was found by band
      shift assays to bind double-stranded oligonucleotide probes with at least two
      internal tandem copies of the maize telomere repeat, TTTAGGG. Point mutations in
      the telomere repeat residues reduced or abolished the binding, whereas rSMH1
      bound nonspecifically to single-stranded DNA probes. The two DNA-binding motifs
      in SMH proteins may provide a link between sequence recognition and chromatin
      dynamics and may function at telomeres or other sites in the nucleus.

PMID- 14576284
TI  - Identification of a locus increasing rice yield and physiological analysis of its
      function.
AB  - I identified a new locus responsible for increased yield potential and evaluated
      its physiological function to understand how to improve potential yield in rice
      (Oryza sativa) plants. Quantitative trait loci (QTLs) for 1,000-grain weight
      (TGW) were analyzed under different environments over 3 years in backcross inbred
      lines of rice japonica cv Nipponbare x indica cv Kasalath. Four QTLs for this
      trait were detected across environments; rice cv Kasalath had a positive allele
      only at one QTL on chromosome 6 (tgw6). A near-isogenic line (NILtgw6) that
      carried a rice cv Kasalath chromosomal segment corresponding to tgw6 in the rice
      cv Nipponbare genetic background was selected and analyzed to clarify the
      physiological function of this locus. The carbohydrate storage capacity before
      heading in NILtgw6 was superior to that in rice cv Nipponbare (control), but
      other characters (e.g. photosynthetic ability in flag leaf and traits related to
      plant type) were the same in both plants. In the leaf sheath, the main organ that
      accumulates carbohydrate before heading in rice, higher contents of carbohydrate
      and transcripts of genes related to starch synthesis were found in NILtgw6 than
      in rice cv Nipponbare. Compared with those in rice cv Nipponbare, a high-yield
      modern cultivar, TGW and yield per plant were significantly higher in NILtgw6, by
      10% and 15%, respectively (P[f] < 0.01). These results suggest that tgw6 improves
      the carbohydrate storage capacity and consequently increases the yield potential
      in NILtgw6.

PMID- 14576285
TI  - Changes in mitochondrial electron partitioning in response to herbicides
      inhibiting branched-chain amino acid biosynthesis in soybean.
AB  - The adaptation of the respiratory metabolism in roots of soybean (Glycine max L.
      Merr. cv Ransom) treated with herbicides that inhibit the enzyme acetolactate
      synthase (ALS) was analyzed. A new gas phase dual-inlet mass spectrometry system
      for simultaneous measurement of 34O2 to 32O2 and O2 to N2 ratios has been
      developed. This system is more accurate than previously described systems, allows
      measurements of much smaller oxygen gradients, and, as a consequence, works with
      tissues that have lower respiration rates. ALS inhibition caused an increase of
      the alternative oxidase (AOX) protein and an accumulation of pyruvate. The
      combination of these two effects is likely to induce the activation of the
      alternative pathway and its participation in the total respiration. Moreover, the
      start of the alternative pathway activation and the increase of AOX protein were
      before the decline in the activity of cytochrome pathway. The possible role of
      AOX under ALS inhibition is discussed.

PMID- 14576287
TI  - Blue light and phytochrome-mediated stomatal opening in the npq1 and phot1 phot2
      mutants of Arabidopsis.
AB  - Recent studies have shown that blue light-specific stomatal opening is reversed
      by green light and that far-red light can be used to probe phytochrome-dependent
      stomatal movements. Here, blue-green reversibility and far-red light were used to
      probe the stomatal responses of the npq1 mutant and the phot1 phot2 double mutant
      of Arabidopsis. In plants grown at 50 micromol m-2 s-1, red light
      (photosynthetic)-mediated opening in isolated stomata from wild type (WT) and
      both mutants saturated at 100 micromol m-2 s-1. Higher fluence rates caused
      stomatal closing, most likely due to photo-inhibition. Blue light-specific
      opening, probed by adding blue light (10 micromol m-2 s-1) to a 100 micromol m-2
      s-1 red background, was found in WT, but not in npq1 or phot1 phot2 double mutant
      stomata. Under 50 micromol m-2 s-1 red light, 10 micromol m-2 s-1 blue light
      opened stomata in both WT and npq1 mutant stomata but not in the phot1 phot2
      double mutant. In npq1, blue light-stimulated opening was reversed by far-red but
      not green light, indicating that npq1 has a phytochrome-mediated response and
      lacks a blue light-specific response. Stomata of the phot1 phot2 double mutant
      opened in response to 20 to 50 micromol m-2 s-1 blue light. This opening was
      green light reversible and far-red light insensitive, indicating that stomata of
      the phot1 phot2 double mutant have a detectable blue light-specific response.

PMID- 14576286
TI  - Tissue-specific and developmentally regulated expression of a cluster of tandemly
      arrayed cell wall-associated kinase-like kinase genes in Arabidopsis.
AB  - The Arabidopsis cell wall-associated kinase (WAK) and WAK-like kinase (WAKL)
      family of receptor-like kinase genes encodes transmembrane proteins with a
      cytoplasmic serine/threonine kinase domain and an extracellular region containing
      epidermal growth factor-like repeats. Previous studies have suggested that some
      WAK members are involved in plant defense and heavy metal responses, whereas
      others are required for cell elongation and plant development. The WAK/WAKL gene
      family consists of 26 members in Arabidopsis and can be divided into four groups.
      Here, we describe the characterization of group 2 members that are composed of a
      cluster of seven tandemly arrayed WAKL genes. The predicted WAKL proteins are
      highly similar in their cytoplasmic region but are more divergent in their
      predicted extracellular ligand-binding region. WAKL7 encodes a truncated WAKL
      isoform that is predicted to be secreted from the cytoplasm. Ratios of
      nonsynonymous to synonymous substitutions suggest that the extracellular region
      is subject to diversifying selection. Comparison of the WAKL and WAK gene
      clusters suggests that they arose independently. Protein gel-blot and
      immunolocalization analyses suggest that WAKL6 is associated with the cell wall.
      Histochemical analyses of WAKL promoters fused with the beta-glucuronidase
      reporter gene have shown that the expressions of WAKL members are developmentally
      regulated and tissue specific. Unlike WAK members whose expressions were found
      predominately in green tissues, WAKL genes are highly expressed in roots and
      flowers. The expression of WAKL5 and WAKL7 can be induced by wounding stress and
      by the salicylic acid analog 2,6-dichloroisonicotinic acid in an nonexpressor of
      pathogenesis-related gene 1-dependent manner, suggesting that they, like some WAK
      members, are wound inducible and can be defined as pathogenesis-related genes.

PMID- 14576288
TI  - An Arabidopsis pex10 null mutant is embryo lethal, implicating peroxisomes in an
      essential role during plant embryogenesis.
AB  - Peroxisomes participate in many important functions in plants, including seed
      reserve mobilization, photorespiration, defense against oxidative stress, and
      auxin and jasmonate signaling. In mammals, defects in peroxisome biogenesis
      result in multiple system abnormalities, severe developmental delay, and death,
      whereas in unicellular yeasts, peroxisomes are dispensable unless required for
      growth of specific substrates. PEX10 encodes an integral membrane protein
      required for peroxisome biogenesis in mammals and yeast. To investigate the
      importance of PEX10 in plants, we characterized a Ds insertion mutant in the
      PEX10 gene of Arabidopsis (AtPEX10). Heterozygous AtPEX10::dissociation element
      mutants show normal vegetative phenotypes under optimal growth conditions, but
      produce about 20% abnormal seeds. The embryos in the abnormal seeds are
      predominantly homozygous for the disruption allele. They show retarded
      development and some morphological abnormalities. No viable homozygous mutant
      plants were obtained. AtPEX10 fused to yellow fluorescent protein colocalized
      with green fluorescent protein-serine-lysine-leucine, a well-documented
      peroxisomal marker, suggesting that AtPEX10 encodes a peroxisomal protein that is
      essential for normal embryo development and viability.

PMID- 14576289
TI  - Knockout analysis of Arabidopsis transcription factors TGA2, TGA5, and TGA6
      reveals their redundant and essential roles in systemic acquired resistance.
AB  - Arabidopsis nonexpresser of pathogenesis-related (PR) genes (NPR1) is the sole
      positive regulator that has been shown to be essential for the induction of
      systemic acquired resistance. In npr1 mutant plants, salicylic acid (SA)-mediated
      PR gene expression and pathogen resistance are abolished completely. NPR1 has
      been shown to interact with three closely related TGA transcription factors-TGA2,
      TGA5, and TGA6-in yeast two-hybrid assays. To elucidate the biological functions
      of these three TGA transcription factors, we analyzed single and combined
      deletion knockout mutants of TGA2, TGA5, and TGA6 for SA-induced PR gene
      expression and pathogen resistance. Induction of PR gene expression and pathogen
      resistance by the SA analog 2,6-dichloroisonicotinic acid (INA) was blocked in
      tga6-1 tga2-1 tga5-1 but not in tga6-1 or tga2-1 tga5-1 plants. Loss of INA
      induced resistance to Peronospora parasitica Noco2 cosegregated with the tga6-1
      mutation in progeny of multiple lines that were heterozygous for tga6-1 and
      homozygous for tga2-1 tga5-1 and could be complemented by genomic clones of wild
      type TGA2 or TGA5, indicating that TGA2, TGA5, and TGA6 encode redundant and
      essential functions in the positive regulation of systemic acquired resistance.
      In addition, tga6-1 tga2-1 tga5-1 plants had reduced tolerance to high levels of
      SA and accumulated higher basal levels of PR-1 under noninducing conditions,
      suggesting that these TGA factors also are important for SA tolerance and the
      negative regulation of the basal expression of PR-1.

PMID- 14576290
TI  - A gain-of-function mutation in a plant disease resistance gene leads to
      constitutive activation of downstream signal transduction pathways in suppressor
      of npr1-1, constitutive 1.
AB  - Plants have evolved sophisticated defense mechanisms against pathogen infections,
      during which resistance (R) genes play central roles in recognizing pathogens and
      initiating defense cascades. Most of the cloned R genes share two common domains:
      the central domain, which encodes a nucleotide binding adaptor shared by APAF-1,
      certain R proteins, and CED-4 (NB-ARC), plus a C-terminal region that encodes Leu
      rich repeats (LRR). In Arabidopsis, a dominant mutant, suppressor of npr1-1,
      constitutive 1 (snc1), was identified previously that constitutively expresses
      pathogenesis-related (PR) genes and resistance against both Pseudomonas syringae
      pv maculicola ES4326 and Peronospora parasitica Noco2. The snc1 mutation was
      mapped to the RPP4 cluster. In snc1, one of the TIR-NB-LRR-type R genes contains
      a point mutation that results in a single amino acid change from Glu to Lys in
      the region between NB-ARC and LRR. Deletions of this R gene in snc1 reverted the
      plants to wild-type morphology and completely abolished constitutive PR gene
      expression and disease resistance. The constitutive activation of the defense
      responses was not the result of the overexpression of the R gene, because its
      expression level was not altered in snc1. Our data suggest that the point
      mutation in snc1 renders the R gene constitutively active without interaction
      with pathogens. To analyze signal transduction pathways downstream of snc1,
      epistasis analyses between snc1 and pad4-1 or eds5-3 were performed. Although the
      resistance signaling in snc1 was fully dependent on PAD4, it was only partially
      affected by blocking salicylic acid (SA) synthesis, suggesting that snc1
      activates both SA-dependent and SA-independent resistance pathways.

PMID- 14576291
TI  - Toward the analysis of the petunia MADS box gene family by reverse and forward
      transposon insertion mutagenesis approaches: B, C, and D floral organ identity
      functions require SEPALLATA-like MADS box genes in petunia.
AB  - We have initiated a systematic functional analysis of the MADS box, intervening
      region, K domain, C domain-type MADS box gene family in petunia. The starting
      point for this has been a reverse-genetics approach, aiming to select for
      transposon insertions into any MADS box gene. We have developed and applied a
      family signature insertion screening protocol that is highly suited for this
      purpose, resulting in the isolation of 32 insertion mutants in 20 different MADS
      box genes. In addition, we identified three more MADS box gene insertion mutants
      using a candidate-gene approach. The defined insertion lines provide a sound
      foundation for a systematic functional analysis of the MADS box gene family in
      petunia. Here, we focus on the analysis of Floral Binding Protein2 (FBP2) and
      FBP5 genes that encode the E-function, which in Arabidopsis has been shown to be
      required for B and C floral organ identity functions. fbp2 mutants display
      sepaloid petals and ectopic inflorescences originating from the third floral
      whorl, whereas fbp5 mutants appear as wild type. In fbp2 fbp5 double mutants,
      reversion of floral organs to leaf-like organs is increased further. Strikingly,
      ovules are replaced by leaf-like structures in the carpel, indicating that in
      addition to the B- and C-functions, the D-function, which specifies ovule
      development, requires E-function activity. Finally, we compare our data with
      results obtained using cosuppression approaches and conclude that the latter
      might be less suited for assigning functions to individual members of the MADS
      box gene family.

PMID- 14576294
TI  - Diversity of type II restriction endonucleases that require two DNA recognition
      sites.
AB  - Orthodox Type IIP restriction endonucleases, which are commonly used in molecular
      biological work, recognize a single palindromic DNA recognition sequence and
      cleave within or near this sequence. Several new studies have reported on
      structural and biochemical peculiarities of restriction endonucleases that differ
      from the orthodox in that they require two copies of a particular DNA recognition
      sequence to cleave the DNA. These two sites requiring restriction endonucleases
      belong to different subtypes of Type II restriction endonucleases, namely Types
      IIE, IIF and IIS. We compare enzymes of these three types with regard to their
      DNA recognition and cleavage properties. The simultaneous recognition of two
      identical DNA sites by these restriction endonucleases ensures that single
      unmethylated recognition sites do not lead to chromosomal DNA cleavage, and might
      reflect evolutionary connections to other DNA processing proteins that
      specifically function with two sites.

PMID- 14576293
TI  - Therapeutic modulation of endogenous gene function by agents with designed DNA
      sequence specificities.
AB  - Designer molecules that can specifically target pre-determined DNA sequences
      provide a means to modulate endogenous gene function. Different classes of
      sequence-specific DNA-binding agents have been developed, including triplex
      forming molecules, synthetic polyamides and designer zinc finger proteins. These
      different types of designer molecules with their different principles of
      engineered sequence specificity are reviewed in this paper. Furthermore, we
      explore and discuss the potential of these molecules as therapeutic modulators of
      endogenous gene function, focusing on modulation by stable gene modification and
      by regulation of gene transcription.

PMID- 14576295
TI  - 8-Hydroxyguanine in a mutational hotspot of the c-Ha-ras gene causes
      misreplication, 'action-at-a-distance' mutagenesis and inhibition of replication.
AB  - Mutations in particular codons of c-Ha-ras have a strong activating potential,
      and an activated ras oncogene has been found in a number of human cancers. Using
      fragments of the human c-Ha-ras gene containing 8-hydroxyguanine (8-OH-G) in
      codon 12, we provide evidence for highly complex biochemical events leading to
      activation of the oncogene. Replication with DNA polymerases alpha (Pol(alpha))
      and beta (Pol(beta)) led to misincorporation of dAMP, while DNA polymerase eta
      (Pol(eta)) caused additional insertion of dGMP. For the first time we report an
      'action-at-a-distance' mutagenic effect for Pol(eta). Replication catalyzed by
      this enzyme resulted in misincorporating dAMP, dTMP and dGMP opposite non
      oxidized guanine 3'-flanked by 8-OH-G. Interestingly, two adjacent 8-OH-G
      residues greatly relaxed the specificity of Pol(eta), which in this system was
      able to incorporate all four nucleotides. Moreover, two adjacent 8-OH-G residues
      completely blocked Pol(alpha) and strongly inhibited Pol(beta), whereas Pol(eta)
      was entirely resistant to this inhibition. These results suggest an important
      role for Pol(eta) in inducing hypermutability in codon 12. Our observations are
      important for understanding the consequences of 8-OH-G being positioned within
      the mutational hot spots of oncogenes, the outcome of which appears to be
      relatively complex even in minimal in vitro systems.

PMID- 14576296
TI  - Exegesis: a procedure to improve gene predictions and its use to find
      immunoglobulin superfamily proteins in the human and mouse genomes.
AB  - Exegesis is a procedure to refine the gene predictions that are produced for
      complex genomes, e.g. those of humans and mice. It uses the program Genewise,
      sequences determined by experiment, experimental maps of gene segment libraries
      and a new browser that allows the user to rapidly inspect and compare multiple
      gene maps to regions of genomic sequences. The procedure should be of general
      use. Here, we use the procedure to find members of the immunoglobulin superfamily
      in the human and mouse genomes. To do this, Exegesis was used to process the
      original gene predictions from the automated Ensembl annotation pipeline.
      Exegesis produced (i) many more complete genes and new transcripts and (ii) a
      mapping of the immunoglobulin and T cell receptor gene libraries to the genome,
      which are largely absent in the Ensembl set.

PMID- 14576297
TI  - Identification of peptide inhibitors of pre-mRNA splicing derived from the
      essential interaction domains of CDC5L and PLRG1.
AB  - CDC5L and PLRG1 are both spliceosomal proteins that are highly conserved across
      species. They have both been shown to be part of sub- spliceosomal protein
      complexes that are essential for pre-mRNA splicing in yeast and humans. CDC5L and
      PLRG1 interact directly in vitro. This interaction is mediated by WD40 regions in
      PLRG1 and the C-terminal domain of CDC5L. In order to determine whether this
      interaction is important for the splicing mechanism, we have designed peptides
      corresponding to highly conserved sequences in the interaction domains of both
      proteins. These peptides were used in in vitro splicing experiments as
      competitors to the cognate sequences in the endogenous proteins. Certain peptides
      derived from the binding domains of both proteins were found to inhibit in vitro
      splicing. This splicing inhibition could be prevented by preincubating the
      peptides with the corresponding partner protein that had been expressed in
      Escherichia coli. The results from this study indicate that the interaction
      between CDC5L and PLRG1 is essential for pre-mRNA splicing and further
      demonstrate that small peptides can be used as effective splicing inhibitors.

PMID- 14576298
TI  - POLQ (Pol theta), a DNA polymerase and DNA-dependent ATPase in human cells.
AB  - The genomes of eukaryotic cells predict the existence of multiple DNA
      polymerases, which are proposed to serve specialized roles in DNA replication and
      repair. We report here the isolation of the full-length human DNA POLQ gene, and
      an initial characterization of its gene product, DNA polymerase theta. POLQ is of
      particular interest as it is orthologous to Drosophila Mus308, a gene implicated
      in cellular resistance to interstrand DNA cross-linking agents. The POLQ cDNA
      encodes a polypeptide of 2592 amino acids with an ATPase-helicase domain in the N
      terminal part of the protein, a central spacer domain, and a DNA polymerase
      domain in the C-terminal portion. This arrangement is conserved with Mus308.
      Expression of an mRNA of approximately 8.5 kb was detected in human cell lines.
      In a survey of human and mouse tissues, expression was highest in testis.
      Immunoblotting with POLQ antibodies detected a protein of >250 kDa in extracts
      from HeLa cells. Prominent fragments of approximately 100 kDa suggest that POLQ
      is readily proteolyzed. Full-length human POLQ was expressed from a baculovirus
      system. Purified POLQ showed DNA polymerase activity on nicked double-stranded
      DNA and on a singly primed DNA template. The enzyme activity was resistant to
      aphidicolin, consistent with its membership of the A family of DNA polymerases,
      and inhibited by dideoxynucleotides. POLQ further exhibited a single-stranded DNA
      dependent ATPase activity.

PMID- 14576299
TI  - Transcriptional response to DNA damage in the archaeon Sulfolobus solfataricus.
AB  - Exposure of cells to DNA-damaging agents triggers a complex biological response
      involving cell cycle arrest and modulation of gene expression. Genomic sequencing
      has revealed the presence of archaeal genes homologous to components of the
      eucaryal nucleotide excision repair (NER) pathway, which is involved in the
      repair of ultraviolet (UV) light-induced DNA damage. However, the events involved
      in the cell response to UV irradiation and their regulation have not been studied
      in Archaea. We show here that UV radiation induces the formation of cyclobutane
      pyrimidine dimers (CPDs) in the hyperthermophilic archaeon Sulfolobus
      solfataricus, and that these lesions are efficiently repaired in vivo in the
      dark, suggesting that a NER pathway is active. DNA damage is a signal for
      concomitant growth arrest and transcriptional induction of the NER genes XPF, XPG
      and XPB. The cell response to UV irradiation includes transcriptional regulation
      of genes encoding two DNA binding proteins involved in chromosome dynamics.
      Moreover, several of these genes are also strongly induced by the intercalating
      agent actinomycin D. Thus, response to DNA damage in S.solfataricus has features
      essentially conserved in all three domains of life.

PMID- 14576300
TI  - Cold-sensitive mutants of Taq DNA polymerase provide a hot start for PCR.
AB  - Although the thermophilic bacterium Thermus aquaticus grows optimally at 70
      degrees C and cannot grow at moderate temperatures, its DNA polymerase I has
      significant activity at 20-37 degrees C. This activity is a bane to some PCRs,
      since it catalyzes non-specific priming. We report mutations of Klentaq (an N
      terminal deletion variant) DNA polymerase that have markedly reduced activity at
      37 degrees C yet retain apparently normal activity at 68 degrees C and resistance
      at 95 degrees C. The first four of these mutations are clustered on the outside
      surface of the enzyme, nowhere near the active site, but at the hinge point of a
      domain that has been proposed to move at each cycle of nucleotide incorporation.
      We show that the novel cold-sensitive mutants can provide a hot start for PCR and
      exhibit slightly improved fidelity.

PMID- 14576301
TI  - A role for c-Myc in the regulation of ribosomal RNA processing.
AB  - The proto-oncogene c-myc encodes a basic helix-loop-helix leucine zipper
      transcription factor (c-Myc) that has a profound role in growth control and cell
      cycle progression. Previous microarray studies identified various classes of c
      Myc target genes, including genes involved in ribosome biogenesis. By screening
      the human B-cell line P493-6 and rat fibroblasts conditionally expressing c-Myc,
      we could substantially extend the list of c-Myc target genes, particularly those
      required for ribosome biogenesis. The identification of 38 new c-Myc target genes
      with nucleolar function, prompted us to investigate processing of ribosomal RNA
      (rRNA). Using pulse-chase labelling experiments we show that c-Myc regulates the
      efficiency of rRNA maturation. In serum-stimulated P493-6 cells, only the
      processing of the 47S rRNA precursor to mature 18S and 28S rRNA, but not the
      synthesis of the 47S transcript, was dependent on the presence of c-Myc. As
      processing of rRNA is sensitive to inhibition of cyclin-dependent kinase (cdk)
      activity by roscovitine, we conclude that c-Myc regulates cell growth and
      proliferation by the coordinated induction of cdk activity and rRNA processing.

PMID- 14576302
TI  - Inhibition of pre-mRNA splicing by synthetic branched nucleic acids.
AB  - The cellular transformation of a precursor mRNA (pre-mRNA) into its mature or
      functional form proceeds by way of a splicing reaction, in which the exons are
      ligated to form the mature linear RNA and the introns are excised as branched or
      lariat RNAs. We have prepared a series of branched compounds (bRNA and bDNA), and
      studied the effects of such molecules on the efficiency of mammalian pre-mRNA
      splicing in vitro. Y-shaped RNAs containing an unnatural L-2'-deoxycytidine unit
      (L-dC) at the 3' termini are highly stabilized against exonuclease hydrolysis in
      HeLa nuclear extracts, and are potent inhibitors of the splicing pathway. A bRNA
      containing internal 2'-O-methyl ribopyrimidine units and L-dC at the 3' ends was
      at least twice as potent as the most potent of the bRNAs containing no 2'
      modifications, with an IC50 of approximately 5 micro M. Inhibitory activity was
      maintained in a branched molecule containing an arabino-adenosine branchpoint
      which, unlike the native bRNAs, resisted cleavage by the lariat- debranching
      enzyme. The data obtained suggest that binding and sequestering of a branch
      recognition factor by the branched nucleic acids is an early event, which occurs
      prior to the first chemical step of splicing. Probably, an early recognition
      element preferentially binds to the synthetic branched molecules over the native
      pre-mRNA. As such, synthetic bRNAs may prove to be invaluable tools for the
      purification and identification of the putative branchpoint recognition factor.

PMID- 14576303
TI  - Gene positional changes relative to the nuclear substructure correlate with the
      proliferating status of hepatocytes during liver regeneration.
AB  - In the interphase nucleus the DNA of higher eukaryotes is organised in loops
      anchored to a proteinaceous substructure variously named but commonly known as
      the nuclear matrix. Important processes of nuclear physiology, such as
      replication, transcription and processing of primary transcripts, occur at
      macromolecular complexes located at discrete sites upon the nuclear substructure.
      The topological relationships between gene sequences located in the DNA loops and
      the nuclear substructure appear to be non-random, thus posing the question of
      whether such relationships remain invariant or change after the critical nuclear
      transitions associated with cell proliferation and tissue regeneration in vivo.
      The hepatocytes are cells that preserve a proliferating capacity that is readily
      displayed after partial ablation of the liver, leading to liver regeneration in
      experimental animals such as the rat. Using this animal model coupled to a
      recently developed PCR-based method for mapping the position of specific DNA
      sequences relative to the nuclear substructure, we provide evidence that
      transient changes in the topological relationships between specific genes and the
      nuclear substructure occur during liver regeneration and that such changes
      correlate with the actual proliferating status of the cells, thus suggesting that
      specific transitions in the higher-order DNA structure are characteristic of the
      quiescent (G0) and replicating (S) phases of the cell cycle in vivo.

PMID- 14576304
TI  - DNA mismatches and GC-rich motifs target transposition by the RAG1/RAG2
      transposase.
AB  - In addition to their essential role in V(D)J recombination, the RAG proteins
      function as a transposase capable of inserting the V(D)J recombination
      intermediate, the signal end DNA fragment, into target DNA. RAG-mediated
      transposition has been suggested to contribute to genome instability and the
      development of lymphoid malignancies. Previous studies suggested that the RAG
      transposase exhibits a target site preference for GC rich sequences and hairpin
      structures. Here we demonstrate that a transposition hot spot (5'-GCCGCCGGGCC
      3'), smaller portions of this hot spot and other GC rich motifs are able to
      target RAG-mediated transposition. Tracks of GC base pairs have been shown to
      have an unusually high rate of base pair breathing. Intriguingly, we find that
      DNA mismatches can efficiently target RAG-mediated transposition and suppress the
      use of other target sites. Hairpins, however, are not generally preferred
      targets. Our results indicate that target DNA melting may be a crucial step
      during RAG-mediated transposition, and that target site selection by the RAG
      transposase may be intimately linked to mutagenic and metabolic processes that
      transiently present favorable DNA structures to the transposition machinery.

PMID- 14576305
TI  - Energetics of echinomycin binding to DNA.
AB  - Differential scanning calorimetry and UV thermal denaturation have been used to
      determine a complete thermodynamic profile for the bis-intercalative interaction
      of the peptide antibiotic echinomycin with DNA. The new calorimetric data are
      consistent with all previously published binding data, and afford the most
      rigorous and direct determination of the binding enthalpy possible. For the
      association of echinomycin with DNA, we found DeltaG degrees = -7.6 kcal mol(-1),
      DeltaH = +3.8 kcal mol(-1) and DeltaS = +38.9 cal mol(-1) K(-1) at 20 degrees C.
      The binding reaction is clearly entropically driven, a hallmark of a process that
      is predominantly stabilized by hydrophobic interactions, though a deeper analysis
      of the free energy contributions suggests that direct molecular recognition
      between echinomycin and DNA, mediated by hydrogen bonding and van der Waals
      contacts, also plays an important role in stabilizing the complex.

PMID- 14576307
TI  - ssDNA-dependent colocalization of adeno-associated virus Rep and herpes simplex
      virus ICP8 in nuclear replication domains.
AB  - The subnuclear distribution of replication complex proteins is being recognized
      as an important factor for the control of DNA replication. Herpes simplex virus
      (HSV) single-strand (ss)DNA-binding protein, ICP8 (infected cell protein 8)
      accumulates in nuclear replication domains. ICP8 also serves as helper function
      for the replication of adeno-associated virus (AAV). Using quantitative 3D
      colocalization analysis we show that upon coinfection of AAV and HSV the AAV
      replication protein Rep and ICP8 co-reside in HSV replication domains. In
      contrast, Rep expressed by a recombinant HSV, in the absence of AAV DNA,
      displayed a nuclear distribution pattern distinct from that of ICP8. Colocal
      ization of Rep and ICP8 was restored by the reintroduction of single-stranded AAV
      vector genomes. In vitro, ICP8 displayed direct binding to Rep78. Single-stranded
      recombinant AAV DNA strongly stimulated this interaction, whereas double-stranded
      DNA was ineffective. Our findings suggest that ICP8 by its strong ssDNA-binding
      activity exploits the unique single-strandedness of the AAV genome to form a
      tripartite complex with Rep78 and AAV ssDNA. This novel mechanism for recruiting
      components of a functional replication complex directs AAV to subnuclear HSV
      replication compartments where the HSV replication complex can replicate the AAV
      genome.

PMID- 14576306
TI  - Poly(ADP-ribose) polymerase-1 is a survival factor for radiation-exposed
      intestinal epithelial stem cells in vivo.
AB  - Poly(ADP-ribose) polymerase-1 (PARP-1) is a key enzyme mediating the cellular
      response to DNA strand breaks. It plays a critical role in genomic stability and
      survival of proliferating cells in culture undergoing DNA damage. Intestinal
      epithelium is the most proliferative tissue in the mammalian body and its stem
      cells show extreme sensitivity to low-level genotoxic stress. We investigated the
      role of PARP-1 in the in vivo damage response of intestinal stem cells in crypts
      of PARP-1-/- and control mice following whole-body gamma-irradiation (1 Gy). In
      the PARP-1-/- mice there was a significant delay during the first 6 h in the
      transient p53 accumulation in stem cells whereas an increased number of cells
      were positive for p21(CIP1/WAF1). Either no or only marginal differences were
      noted in MDM2 expression, apoptosis, induction of or recovery from mitotic
      blockage, or inhibition of DNA synthesis. We further observed a dose-dependent
      reduction in crypt survival measured at 4 days post-irradiation in control mice,
      and this crypt-killing effect was significantly potentiated in PARP-1-/- mice.
      Our results thus establish that PARP-1 acts as a survival factor for intestinal
      stem cells in vivo and suggest a functional link with early p53 and
      p21(CIP1/WAF1) responses.

PMID- 14576308
TI  - Splice site prediction with quadratic discriminant analysis using diversity
      measure.
AB  - Based on the conservation of nucleotides at splicing sites and the features of
      base composition and base correlation around these sites we use the method of
      increment of diversity combined with quadratic discriminant analysis (IDQD) to
      study the dependence structure of splicing sites and predict the exons/introns
      and their boundaries for four model genomes: Caenorhabditis elegans, Arabidopsis
      thaliana, Drosophila melanogaster and human. The comparison of compositional
      features between two sequences and the comparison of base dependencies at
      adjacent or non-adjacent positions of two sequences can be integrated
      automatically in the increment of diversity (ID). Eight feature variables around
      a potential splice site are defined in terms of ID. They are integrated in a
      single formal framework given by IDQD. In our calculations 7 (8) base region
      around the donor (acceptor) sites have been considered in studying the
      conservation of nucleotides and sequences of 48 bp on either side of splice sites
      have been used in studying the compositional and base-correlating features. The
      windows are enlarged to 16 (donor), 29 (acceptor) and 80 bp (either side) to
      improve the prediction for human splice sites. The prediction capability of the
      present method is comparable with the leading splice site detector--GeneSplicer.

PMID- 14576309
TI  - Recognition of threosyl nucleotides by DNA and RNA polymerases.
AB  - Alpha-L-threose nucleic acids (TNA) are potentially natural nucleic acids that
      could have acted as an evolutionary alternative to RNA. We determined whether DNA
      or RNA polymerases could recognize phosphorylated threosyl nucleosides. We found
      that for both the Vent (exo-) DNA polymerase and HIV reverse transcriptase K(m)
      values were increased and kcat values decreased for the incorporation of tTTP in
      comparison to their natural counterparts. Our results suggest that TNA may have
      played a role in the evolution of the DNA-RNA-protein world. Thus, TNA may be a
      candidate for further studies in evolutionary chemistry and biology.

PMID- 14576310
TI  - Groove-binding unsymmetrical cyanine dyes for staining of DNA: syntheses and
      characterization of the DNA-binding.
AB  - Two new crescent-shaped unsymmetrical cyanine dyes have been synthesised and
      their interactions with DNA have been investigated by different spectroscopic
      methods. These dyes are analogues to a minor groove binding unsymmetrical cyanine
      dye, BEBO, recently reported by us. In this dye, the structure of the known
      intercalating cyanine dye BO was extended with a benzothiazole substituent. To
      investigate how the identity of the extending heterocycle affects the binding to
      DNA, the new dyes BETO and BOXTO have a benzothiazole group and a benzoxazole
      moiety, respectively. Whereas BEBO showed a heterogeneous binding to calf thymus
      DNA, linear and circular dichroism studies of BOXTO indicate a high preference
      for minor groove binding. BETO also binds in the minor groove to mixed sequence
      DNA but has a contribution of non-ordered and non-emissive species present. A non
      intercalative binding mode of the new dyes, as well as for BEBO, is further
      supported by electrophoresis unwinding assays. These dyes, having comparable
      spectral properties as the intercalating cyanine dyes, but bind in the minor
      groove instead, might be useful complements for staining of DNA. In particular,
      the benzoxazole substituted dye BOXTO has attractive fluorescence properties with
      a quantum yield of 0.52 when bound to mixed sequence DNA and a 300-fold increase
      in fluorescence intensity upon binding.

PMID- 14576311
TI  - Groove-binding unsymmetrical cyanine dyes for staining of DNA: dissociation rates
      in free solution and electrophoresis gels.
AB  - The rates of dissociation of three non-intercalative unsymmetrical cyanine dyes,
      BEBO, BETO and BOXTO from mixed-sequence DNA have been studied with the DNA
      either free in solution or in confining porous agarose gels. The properties of
      the new dyes were compared to the related intercalating dyes BO, BO-PRO, TO-PRO
      and YO-PRO. With DNA in solution, BEBO dissociates more slowly than the
      monovalent BO and interestingly also more slowly than the divalent dye BO-PRO.
      Similarly, both BETO and BOXTO exhibit considerably slower dissociation than TO
      PRO. The new dyes show biexponential dissociation kinetics in mixed-sequence DNA.
      The average rate of dissociation increases with increasing ionic strength, but
      the salt dependence of the dissociation is weaker than for the corresponding
      intercalating dye. The rate of dye-dissociation decreases by a factor of about
      10(5) in the gel. The rates for the dyes generally follow the pattern that we
      observe with the DNA in free solution, however a more accentuated stabilization
      was seen for intercalators than for groove-bound dyes. The results show that, in
      particular, BOXTO is a promising candidate as a preferentially groove-bound DNA
      stain with a large enhancement of the fluorescence quantum yield upon binding to
      DNA, and which exhibits slow and salt-insensitive dissociation compared to
      corresponding intercalative dyes.

PMID- 14576312
TI  - The fragile X syndrome repeats form RNA hairpins that do not activate the
      interferon-inducible protein kinase, PKR, but are cut by Dicer.
AB  - We show here that under physiologically reasonable conditions, CGG repeats in RNA
      readily form hairpins. In contrast to its DNA counterpart that forms a complex
      mixture of hairpins and tetraplexes, r(CGG)22 forms a single stable hairpin with
      no evidence for any other folded structure even at low pH. RNA with the sequence
      (CGG)9AGG (CGG)12AGG(CGG)97, found in a fragile X syndrome pre-mutation allele,
      forms a number of different hairpins. The most prominent hairpin forms in the 3'
      part of the repeat and involves the 97 uninterrupted CGG repeats. In contrast to
      the CUG-RNA hairpins formed by myotonic dystrophy type 1 repeats, we found no
      evidence that CGG-RNA hairpins activate PKR, the interferon-inducible protein
      kinase that is activated by a wide range of double-stranded RNAs. However, we do
      show that the CGG-RNA is digested, albeit inefficiently, by the human Dicer
      enzyme, a step central to the RNA interference effect on gene expression. These
      data provide clues to the basis of the toxic effect of CGG-RNA that is thought to
      occur in fragile X pre-mutation carriers. In addition, RNA hairpins may also
      account for the stalling of the 40S ribosomal subunit that is thought to
      contribute to the translation deficit in fragile X pre-mutation and full mutation
      alleles.

PMID- 14576313
TI  - Automated identification of RNA conformational motifs: theory and application to
      the HM LSU 23S rRNA.
AB  - We develop novel methods for recognizing and cataloging conformational states of
      RNA, and for discovering statistical rules governing those states. We focus on
      the conformation of the large ribosomal subunit from Haloarcula marismortui. The
      two approaches described here involve torsion matching and binning. Torsion
      matching is a pattern-recognition code which finds structural repetitions.
      Binning is a classification technique based on distributional models of the data.
      In comparing the results of the two methods we have tested the hypothesis that
      the conformation of a very large complex RNA molecule can be described accurately
      by a limited number of discrete conformational states. We identify and eliminate
      extraneous and redundant information without losing accuracy. We conclude, as
      expected, that four of the torsion angles contain the overwhelming bulk of the
      structural information. That information is not significantly compromised by
      binning the continuous torsional information into a limited number of discrete
      values. The correspondence between torsion matching and binning is 99% (per
      residue). Binning, however, does have several advantages. In particular, we
      demonstrate that the conformation of a large complex RNA molecule can be
      represented by a small alphabet. In addition, the binning method lends itself to
      a natural graphical representation using trees.

PMID- 14576314
TI  - Repair of oxidative DNA damage by amino acids.
AB  - Guanyl radicals, the product of the removal of a single electron from guanine,
      are produced in DNA by the direct effect of ionizing radiation. We have produced
      guanyl radicals in DNA by using the single electron oxidizing agent (SCN)2-,
      itself derived from the indirect effect of ionizing radiation via thiocyanate
      scavenging of OH. We have examined the reactivity of guanyl radicals in plasmid
      DNA with the six most easily oxidized amino acids cysteine, cystine, histidine,
      methionine, tryptophan and tyrosine and also simple ester and amide derivatives
      of them. Cystine and histidine derivatives are unreactive. Cysteine, methionine,
      tyrosine and particularly tryptophan derivatives react to repair guanyl radicals
      in plasmid DNA with rate constants in the region of approximately 10(5), 10(5),
      10(6) and 10(7) dm3 mol(-1) s(-1), respectively. The implication is that amino
      acid residues in DNA binding proteins such as histones might be able to repair by
      an electron transfer reaction the DNA damage produced by the direct effect of
      ionizing radiation or by other oxidative insults.

PMID- 14576315
TI  - U2AF modulates poly(A) length control by the poly(A)-limiting element.
AB  - The poly(A)-limiting element (PLE) restricts the length of the poly(A) tail to
      <20 nt when present in the terminal exon of a pre-mRNA. We previously identified
      a 65 kDa protein that could be cross-linked to a functional PLE, but not to an
      inactive mutant element. This binding was competed by poly(U) and poly(C), but
      not poly(A) or poly(G). Selectivity for the pyrimidine-rich portion of the PLE
      was demonstrated by RNase footprinting of the binding activity in total nuclear
      extract. A 65 kDa protein that selectively cross-linked to the functional PLE was
      purified by conventional chromatography and identified as the large subunit of U2
      snRNP auxiliary factor (U2AF). Overexpression of U2AF65 in cells transfected with
      a PLE-containing reporter construct resulted in the appearance of a population of
      mRNAs with heterogeneous poly(A) tails. However, this effect was lost following
      deletion of the C-terminal RNA recognition motifs (RRMs). A C-->G mutation
      following the AG dinucleotide in the PLE resulted in mRNA with poly(A) ranging
      from 25-50 nt. This reverted to a discrete, <20 nt poly(A) tail in cells
      expressing U2AF65. Our results suggest that U2AF modulates the function of the
      PLE, perhaps by facilitating the binding of another protein to the element.

PMID- 14576316
TI  - Possible anti-recombinogenic role of Bloom's syndrome helicase in double-strand
      break processing.
AB  - Bloom's syndrome (BS) which associates genetic instability and predisposition to
      cancer is caused by mutations in the BLM gene encoding a RecQ family 3'-5' DNA
      helicase. It has been proposed that the generation of genetic instability in BS
      cells could result from an aberrant non-homologous DNA end joining (NHEJ), one of
      the two main DNA double-strand break (DSB) repair pathways in mammalian cells,
      the second major pathway being homologous recombination (HR). Using cell
      extracts, we report first that Ku70/80 and the catalytic subunit of the DNA
      dependent protein kinase (DNA-PKcs), key factors of the end-joining machinery,
      and BLM are located in close proximity on DNA and that BLM binds to DNA only in
      the absence of ATP. In the presence of ATP, BLM is phosphorylated and dissociates
      from DNA in a strictly DNA-PKcs-dependent manner. We also show that BS cells
      display, in vivo, an accurate joining of DSBs, reflecting thus a functional NHEJ
      pathway. In sharp contrast, a 5-fold increase of the HR-mediated DNA DSB repair
      in BS cells was observed. These results support a model in which NHEJ activation
      mediates BLM dissociation from DNA, whereas, under conditions where HR is
      favored, e.g. at the replication fork, BLM exhibits an anti-recombinogenic role.

PMID- 14576317
TI  - Functional modules by relating protein interaction networks and gene expression.
AB  - Genes and proteins are organized on the basis of their particular mutual
      relations or according to their interactions in cellular and genetic networks.
      These include metabolic or signaling pathways and protein interaction, regulatory
      or co-expression networks. Integrating the information from the different types
      of networks may lead to the notion of a functional network and functional
      modules. To find these modules, we propose a new technique which is based on
      collective, multi-body correlations in a genetic network. We calculated the
      correlation strength of a group of genes (e.g. in the co-expression network)
      which were identified as members of a module in a different network (e.g. in the
      protein interaction network) and estimated the probability that this correlation
      strength was found by chance. Groups of genes with a significant correlation
      strength in different networks have a high probability that they perform the same
      function. Here, we propose evaluating the multi-body correlations by applying the
      superparamagnetic approach. We compare our method to the presently applied mean
      Pearson correlations and show that our method is more sensitive in revealing
      functional relationships.

PMID- 14576319
TI  - Transcription profiles of the bacterium Mycoplasma pneumoniae grown at different
      temperatures.
AB  - Applying microarray technology, we have investigated the transcriptome of the
      small bacterium Mycoplasma pneumoniae grown at three different temperature
      conditions: 32, 37 and 32 degrees C followed by a heat shock for 15 min at 43
      degrees C, before isolating the RNA. From 688 proposed open-reading frames, 676
      were investigated and 564 were found to be expressed (P < 0.001; 606 with P <
      0.01) and at least 33 (P < 0.001; 77 at P < 0.01) regulated. By quantitative real
      time PCR of selected mRNA species, the expression data could be linked to
      absolute molecule numbers. We found M.pneumoniae to be regulated at the
      transcriptional level. Forty-seven genes were found to be significantly up
      regulated after heat shock (P < 0.01). Among those were the conserved heat shock
      genes like dnaK, lonA and clpB, but also several genes coding for ribosomal
      proteins and 10 genes of unassigned functions. In addition, 30 genes were found
      to be down-regulated under the applied heat shock conditions. Further more, we
      have compared different methods of cDNA synthesis (random hexamer versus gene
      specific primers, different RNA concentrations) and various normalization
      strategies of the raw microarray data.

PMID- 14576318
TI  - Functional dissection of the mouse tyrosinase locus control region identifies a
      new putative boundary activity.
AB  - Locus control regions (LCRs) are complex high-order chromatin structures
      harbouring several regulatory elements, including enhancers and boundaries. We
      have analysed the mouse tyrosinase LCR functions, in vitro, in cell lines and, in
      vivo, in transgenic mice and flies. The LCR-core (2.1 kb), located at -15 kb and
      carrying a previously described tissue-specific DNase I hypersensitive site,
      operates as a transcriptional enhancer that efficiently transactivates
      heterologous promoters in a cell-specific orientation-independent manner.
      Furthermore, we have investigated the boundary activity of these sequences in
      transgenic animals and cells. In mice, the LCR fragment (3.7 kb) rescued a weakly
      expressed reference construct that displays position effects. In Drosophila, the
      LCR fragment and its core insulated the expression of a white minigene reporter
      construct from chromosomal position effects. In cells, sequences located 5' from
      the LCR-core displayed putative boundary activities. We have obtained genomic
      sequences surrounding the LCR fragment and found a LINE1 repeated element at 5'.
      In B16 melanoma and L929 fibroblast mouse cells, this element was found heavily
      methylated, supporting the existence of putative boundary elements that could
      prevent the spreading of condensed chromatin from the LINE1 sequences into the
      LCR fragment, experimentally shown to be in an open chromatin structure.

PMID- 14576320
TI  - Intrinsic differences between authentic and cryptic 5' splice sites.
AB  - Cryptic splice sites are used only when use of a natural splice site is disrupted
      by mutation. To determine the features that distinguish authentic from cryptic 5'
      splice sites (5'ss), we systematically analyzed a set of 76 cryptic 5'ss derived
      from 46 human genes. These cryptic 5'ss have a similar frequency distribution in
      exons and introns, and are usually located close to the authentic 5'ss.
      Statistical analysis of the strengths of the 5'ss using the Shapiro and Senapathy
      matrix revealed that authentic 5'ss have significantly higher score values than
      cryptic 5'ss, which in turn have higher values than the mutant ones. beta-Globin
      provides an interesting exception to this rule, so we chose it for detailed
      experimental analysis in vitro. We found that the sequences of the beta-globin
      authentic and cryptic 5'ss, but not their surrounding context, determine the
      correct 5'ss choice, although their respective scores do not reflect this
      functional difference. Our analysis provides a statistical basis to explain the
      competitive advantage of authentic over cryptic 5'ss in most cases, and should
      facilitate the development of tools to reliably predict the effect of disease
      associated 5'ss-disrupting mutations at the mRNA level.

PMID- 14576321
TI  - Human EFO1p exhibits acetyltransferase activity and is a unique combination of
      linker histone and Ctf7p/Eco1p chromatid cohesion establishment domains.
AB  - Proper segregation of chromosomes during mitosis requires that the products of
      chromosome replication are paired together-termed sister chromatid cohesion. In
      budding yeast, Ctf7p/Eco1p is an essential protein that establishes cohesion
      between sister chromatids during S phase. In fission yeast, Eso1p also functions
      in cohesion establishment, but is comprised of a Ctf7p/Eco1p domain fused to a
      Rad30p domain (a DNA polymerase) both of which are independently expressed in
      budding yeast. In this report, we identify and characterize the first candidate
      human ortholog of Ctf7p/Eco1p, which we term hEFO1p (human Establishment Factor
      Ortholog). As in fission yeast Eso1p, the hEFO1p open reading frame extends well
      upstream of the C-terminal Ctf7p/Eco1p domain. However, this N-terminal extension
      in hEFO1p is unlike Rad30p, but instead exhibits significant homology to linker
      histone proteins. Thus, hEFO1p is a unique fusion of linker histone and cohesion
      establishment domains. hEFO1p is widely expressed among the tissues tested.
      Consistent with a role in chromosome segregation, hEFO1p localizes exclusively to
      the nucleus when expressed in HeLa tissue culture cells. Moreover, biochemical
      analyses reveal that hEFO1p exhibits acetyltransferase activity. These findings
      document the first characterization of a novel human acetyltransferase, hEFO1p,
      that is comprised of both linker histone and Ctf7p/Eco1p domains.

PMID- 14576322
TI  - Characterisation of new substrate specificities of Escherichia coli and
      Saccharomyces cerevisiae AP endonucleases.
AB  - Despite the progress in understanding the base excision repair (BER) pathway it
      is still unclear why known mutants deficient in DNA glycosylases that remove
      oxidised bases are not sensitive to oxidising agents. One of the back-up repair
      pathways for oxidative DNA damage is the nucleotide incision repair (NIR) pathway
      initiated by two homologous AP endonucleases: the Nfo protein from Escherichia
      coli and Apn1 protein from Saccharomyces cerevisiae. These endonucleases nick
      oxidatively damaged DNA in a DNA glycosylase-independent manner, providing the
      correct ends for DNA synthesis coupled to repair of the remaining 5'-dangling
      nucleotide. NIR provides an advantage compared to DNA glycosylase-mediated BER,
      because AP sites, very toxic DNA glycosylase products, do not form. Here, for the
      first time, we have characterised the substrate specificity of the Apn1 protein
      towards 5,6-dihydropyrimidine, 5-hydroxy-2'-deoxyuridine and 2,6-diamino-4
      hydroxy-5-N-methylformamidopyrimidine deoxynucleotide. Detailed kinetic
      comparisons of Nfo, Apn1 and various DNA glycosylases using different DNA
      substrates were made. The apparent K(m) and kcat/K(m) values of the reactions
      suggest that in vitro DNA glycosylase/AP lyase is somewhat more efficient than
      the AP endonuclease. However, in vivo, using cell-free extracts from paraquat
      induced E.coli and from S.cerevisiae, we show that NIR is one of the major
      pathways for repair of oxidative DNA base damage.

PMID- 14576323
TI  - Matrix attachment region (MAR) properties and abnormal expansion of AT island
      minisatellites in FRA16B fragile sites in leukemic CEM cells.
AB  - AT-rich minisatellites (AT islands) are sites of genomic instability in cancer
      cells and targets for extremely lethal AT-specific drugs, such as bizelesin. Here
      we investigated the AT islands in the FRA16B fragile site region for their
      possible roles in the organization of DNA on the nuclear matrix. The FRA16B AT
      island nominally spans approximately 3 kb of mostly >90% A/T DNA. In silico
      analysis indicates that this domain exhibits characteristics of nuclear matrix
      attachment regions (MARs): an exceptionally intense computed 'MAR potential' and
      profound duplex destabilization and flexibility. FRA16B repeats specifically bind
      to isolated nuclear matrices, which indicates their in vitro MAR function. This
      binding is several-fold greater than that of a known MAR in the c-myc gene. AT
      islands in fragile sites FRA16B and FRA16D are significantly more abundant in CEM
      cells that are hypersensitive to bizelesin compared to normal WI-38 cells. FRA16B
      overabundance in CEM is due to an approximately 10-fold expansion of FRA16B
      repeats. The expanded FRA16B minisatellites in CEM cells preferentially localize
      to the nuclear matrix-associated DNA indicating their in vivo MAR function. The
      unexpanded repeats in WI-38 cells localize to the loop DNA. The c-myc MAR is also
      matrix-associated in CEM cells while localizing to loop DNA in WI-38 cells. These
      results are the first to demonstrate that AT islands in fragile sites can
      function as MARs both in vitro and in vivo. The ability of FRA16B-mediated MAR
      sites to rearrange depending on the repeat expansion status could be relevant to
      both genomic instability of cancer cells and their sensitivity to AT-island
      targeting drugs.

PMID- 14576324
TI  - Expanding the design horizon of antisense oligonucleotides with alpha-L-LNA.
AB  - Oligonucleotides containing Locked Nucleic Acids (LNA) to various extents and at
      various positions were evaluated for antisense activity, RNase H recruitment,
      nuclease stability and thermal affinity. In this work, two different
      diastereoisomers of LNA were studied: the beta-D-LNA and the alpha-L-LNA
      (abbreviated as beta-D-LNA and alpha-L-LNA). Our findings show that the best
      antisense activity with 16mer gapmers containing beta-D-LNA (oligonucleotides
      containing consecutive segments of LNA and DNA with a central DNA stretch flanked
      by two LNA segments, LNA-DNA-LNA) is found with gap sizes between 7 and 10 nt.
      The optimal gap size is motif-dependent, and requires the right balance between
      gap size and affinity. Compared to beta-D-LNA, alpha-L-LNA shows superior
      stability against a 3'-exonuclease. The design possibilities of alpha-L-LNA were
      explored for different gapmers and other designs, collectively called chimeras.
      The placement of alpha-L-LNA in the junctions or in the flanks resulted in potent
      antisense oligonucleotides. Moreover, different chimeras with an alternate
      composition of DNA, alpha-L-LNA and beta-D-LNA were evaluated in terms of
      antisense activity and RNase H recruitment. Chimeras with an interrupted DNA
      stretch with alpha-L-LNA still recruit RNase H and show good levels of antisense
      activity, while the same design with beta-D-LNA results in a drop in antisense
      potency. Our findings indicate that alpha-L-LNA is a powerful and versatile
      nucleotide analogue for designing potent antisense oligonucleotides.

PMID- 14576325
TI  - Triplex hydration: nanosecond molecular dynamics simulation of the solvated
      triplex formed by mixed sequences.
AB  - A theoretical model for the hydration pattern and motion of ions around the
      triple helical DNA with mixed sequences d(GACTGGTGAC)d(GTCACCAGTC)*d(GACTGGTGAC)
      in solution, during MD simulation, using the particle mesh Ewald sum method, is
      elaborated here. The AMBER 5.0 force field has been used during the simulation in
      solvent. The simulation studies support a dynamically stable atmosphere around
      the DNA triplex in solution over the entire length of the trajectory. The results
      have been compared with Hoogsteen triplexes and examined in the context of the
      observed behaviour of hydration in crystallographic data of duplexes. The
      dynamical organization of counterions and water molecules around the triplex
      formed by mixed sequences is described here. It has been observed that cations
      prefer to bind between two adjoining purines of the second and the third strands.
      The idea of localized complexes (mobile counterions in unspecific electronegative
      pockets around the DNA triplex with water molecules) may have important
      implications for understanding the specificity of the interactions of nucleic
      acids with proteins and other ligands.

PMID- 14576326
TI  - Enhanced crossover SCRATCHY: construction and high-throughput screening of a
      combinatorial library containing multiple non-homologous crossovers.
AB  - SCRATCHY is a methodology for the construction of libraries of chimeras between
      genes that display low sequence homology. We have developed a strategy for
      library creation termed enhanced crossover SCRATCHY, that significantly increases
      the number of clones containing multiple crossovers. Complementary chimeric gene
      libraries generated by incremental truncation (ITCHY) of two distinct parental
      sequences are created, and are then divided into arbitrarily defined sections.
      The respective sections are amplified by skewed sets of primers (i.e. a
      combination of gene A specific forward primer and gene B specific reverse primer,
      etc.) allowing DNA fragments containing non-homologous crossover points to be
      amplified. The amplified chimeric sections are then subjected to a DNA shuffling
      process generating an enhanced crossover SCRATCHY library. We have constructed
      such a library using the rat theta 2 glutathione transferase (rGSTT2) and the
      human theta 1 glutathione transferase (hGSTT1) genes (63% DNA sequence identity).
      DNA sequencing analysis of unselected library members revealed a greater
      diversity than that obtained by canonical family shuffling or with conventional
      SCRATCHY. Expression and high-throughput flow cytometric screening of the
      chimeric GST library identified several chimeric progeny that retained rat-like
      parental substrate specificity.

PMID- 14576327
TI  - Inducible shRNA expression for application in a prostate cancer mouse model.
AB  - RNA interference (RNAi) is a powerful tool to induce loss-of-function phenotypes
      by inhibiting gene expression post-transcriptionally. Synthetic short interfering
      RNAs (siRNAs) as well as vector-based siRNA expression systems have been used
      successfully to silence gene expression in a variety of biological systems. We
      describe the development of an inducible siRNA expression system that is based on
      the tetracycline repressor and eukaryotic RNA polymerase III promoters (U6 and
      7SK). For proof of concept we selectively inhibited expression of two catalytic
      subunits of the phosphatidylinositol 3-kinase (PI 3-kinase), p110alpha and
      p110beta, by using vector-derived short hairpin RNAs (shRNAs). Stable pools of
      human prostate cancer cells (PC-3) exhibiting reduced levels of both PI 3-kinase
      catalytic subunits due to the expression of corresponding shRNAs in an inducible
      fashion were established and analyzed for their invasive potential in vitro as
      well as in an orthotopic metastatic mouse model. This inducible system for RNAi
      allows an unbiased and comparable analysis of loss-of-function phenotypes by
      comparing selected isogenic cell populations on the induced and non-induced
      level. In addition, conditional RNAi allows the study of essential and
      multifunctional genes involved in complex biological processes by preventing
      inhibitory and compensatory effects caused by constitutive knockdown.

PMID- 14576328
TI  - Exploiting features of adenovirus replication to support mammalian kinase
      production.
AB  - Faced with the current wealth of genomic data, it is essential to have robust and
      reliable methods of converting DNA sequences into their functional gene products.
      We demonstrate here that when conditions are established that take advantage of
      the replication-associated virus amplification, the virus-induced shutdown of
      host protein synthesis as well as the activation of signalling pathways that
      normally occur during virus replication, adenovirus biology can be exploited to
      generate a potent kinase expression system. Residual virus in the protein
      production has always been a limitation for adenovirus systems and we describe a
      DNA intercalator/ultraviolet light treatment that eliminates residual adenovirus
      in protein preparations that has no deleterious effect on enzyme activity. The
      use of mammalian cells in combination with adenovirus generated a variety of
      active enzymes which could not be produced in Escherichia coli or baculovirus
      infected insect cells. Thus, the utility of adenovirus-mediated enzyme expression
      as a versatile alternative to established protein production technologies is
      demonstrated.

PMID- 14576329
TI  - Quantitative evaluation by minisequencing and microarrays reveals accurate
      multiplexed SNP genotyping of whole genome amplified DNA.
AB  - Whole genome amplification (WGA) procedures such as primer extension
      preamplification (PEP) or multiple displacement amplification (MDA) have the
      potential to provide an unlimited source of DNA for large-scale genetic studies.
      We have performed a quantitative evaluation of PEP and MDA for genotyping single
      nucleotide polymorphisms (SNPs) using multiplex, four-color fluorescent
      minisequencing in a microarray format. Forty-five SNPs were genotyped and the WGA
      methods were evaluated with respect to genotyping success, signal-to-noise
      ratios, power of genotype discrimination, yield and imbalanced amplification of
      alleles in the MDA product. Both PEP and MDA products provided genotyping results
      with a high concordance to genomic DNA. For PEP products the power of genotype
      discrimination was lower than for MDA due to a 2-fold lower signal-to-noise
      ratio. MDA products were indistinguishable from genomic DNA in all aspects
      studied. To obtain faithful representation of the SNP alleles at least 0.3 ng DNA
      should be used per MDA reaction. We conclude that the use of WGA, and MDA in
      particular, is a highly promising procedure for producing DNA in sufficient
      amounts even for genome wide SNP mapping studies.

PMID- 14576332
TI  - DANCER: a program for digital anatomical reconstruction of gene expression data.
AB  - A digital anatomy construction (DANCER) program was developed for gene expression
      data. DANCER can be used to reconstruct anatomical images from in situ
      hybridization images, microarray or other gene expression data. The program fills
      regions of a drawn figure with the corresponding values from a gene expression
      data set. The output of the program presents the expression levels of a
      particular gene in a particular region relative to other regions. The program was
      tested with values from experimental in situ hybridization autoradiographs and
      from a microarray experiment. Reconstruction of in situ hybridization data from
      adult rat brain made by DANCER corresponded well with the original
      autoradiograph. Reconstruction of microarray data from adult mouse brains
      provided images that reflect actual expression levels. This program should help
      to provide visualization and interpretation of data derived from gene expression
      experiments. DANCER may be freely downloaded.

PMID- 14576330
TI  - Short bioactive Spiegelmers to migraine-associated calcitonin gene-related
      peptide rapidly identified by a novel approach: tailored-SELEX.
AB  - We developed an integrated method to identify aptamers with only 10 fixed
      nucleotides through ligation and removal of primer binding sites within the
      systematic evolution of ligands by exponential enrichment (SELEX) process. This
      Tailored-SELEX approach was validated by identifying a Spiegelmer ('mirror-image
      aptamer') that inhibits the action of the migraine-associated target calcitonin
      gene-related peptide 1 (alpha-CGRP) with an IC50 of 3 nM at 37 degrees C in cell
      culture. Aptamers are oligonucleotide ligands that can be generated to bind to
      targets with high affinity and specificity. Stabilized aptamers and Spiegelmers
      have shown activity in vivo and may be used as therapeutics. Aptamers are
      isolated by in vitro selection from combinatorial nucleic acid libraries that are
      composed of a central randomized region and additional fixed primer binding sites
      with approximately 30-40 nt. The identified sequences are usually not short
      enough for efficient chemical Spiegelmer synthesis, post-SELEX stabilization of
      aptamers and economical production. If the terminal primer binding sites are part
      of the target recognizing domain, truncation of aptamers has proven difficult and
      laborious. Tailored-SELEX results in short sequences that can be tested more
      rapidly in biological systems. Currently, our identified CGRP binding Spiegelmer
      serves as a lead compound for in vivo studies.

PMID- 14576331
TI  - Regulation of Cre recombinase by ligand-induced complementation of inactive
      fragments.
AB  - Cre recombinase is extensively used to engineer the genome of experimental
      animals. However, its usefulness is still limited by the lack of an efficient
      temporal control over its activity. To overcome this, we have developed DiCre, a
      regulatable fragment complementation system for Cre. The enzyme was split into
      two moieties that were fused to FKBP12 (FK506-binding protein) and FRB (binding
      domain of the FKBP12-rapamycin-associated protein), respectively. These can be
      efficiently heterodimerized by rapamycin. Several variants, based on splitting
      Cre at different sites and using different linker peptides, were tested in an
      indicator cell line. The fusion proteins, taken separately, had no recombinase
      activity. Stable transformants, co-expressing complementing fragments based on
      splitting Cre between Asn59 and Asn60, displayed low background activity
      affecting 0.05-0.4% of the cells. Rapamycin induced a rapid recombination,
      reaching 100% by 48-72 h, with an EC50 of 0.02 nM. Thus, ligand-induced
      dimerization can efficiently regulate Cre, and should be useful to achieve a
      tight temporal control of its activity, such as in the case of the creation of
      conditional knock-out animals.

PMID- 14576333
TI  - One step assembly of multiple DNA fragments with a designed order and orientation
      in Bacillus subtilis plasmid.
AB  - A universal method to reconstitute sets of genes was developed. Owing to the
      intrinsic nature of the plasmid establishment mechanism in Bacillus subtilis, the
      assembly of five antibiotic resistance genes with a defined order and orientation
      was achieved. These five fragments and the plasmid have three-base protruding
      sequences at both ends. The protruding sequences are designed so that each
      fragment is ligated once in a row according to the pairing. Ligation by T4 DNA
      ligase in the presence of 150 mM NaCl and 10% polyethylene glycol at 37 degrees C
      yielded high molecular tandem repeat linear form DNA. This multimeric form of DNA
      was preferentially used for plasmid establishment in B.subtilis. The method,
      referred to as Ordered Gene Assembly in B.subtilis (OGAB), allows for the design
      of multiple fragments with very high efficiency and great fidelity.

PMID- 14576334
TI  - Efficient labeling of fission yeast Schizosaccharomyces pombe with thymidine and
      BUdR.
AB  - In this paper we report the construction of a Schizosaccharomyces pombe strain
      that facilitates analysis of replicating DNA. The strain co-expresses the Herpes
      simplex virus thymidine kinase gene (hsv-tk) and a human equilibrative nucleoside
      transporter (hENT1). The double integrant efficiently incorporates 3H-thymidine
      into nuclear DNA as monitored by scintillation counting. These strains also
      incorporate the thymidine analog Bromodeoxy uridine (BUdR) into newly replicated
      DNA, which can be detected by immunofluorescence and flow cytometry. This strain
      provides a valuable tool for direct study of DNA replication in S.pombe.

PMID- 14576335
TI  - Rapid purification of RNA secondary structures.
AB  - A new method for rapid purification and structural analysis of
      oligoribonucleotides of 19 and 20 nt is applied to RNA hairpins SL3 and SL2,
      which are stable secondary structures present on the psi recognition element of
      HIV-1. This approach uses ion-pairing reversed-phase liquid chromatography (IP
      RPLC) to achieve the separation of the stem-loop from the transcription mix.
      Evidence is presented that IP-RPLC is sensitive to the different conformers of
      these secondary structures. The purity of each stem-loop was confirmed by mass
      spectrometry and PAGE. IP-RPLC purification was found to be superior to PAGE in
      terms of time, safety and, most importantly, purity.

PMID- 14576336
TI  - Neurogenin3 activates the islet differentiation program while repressing its own
      expression.
AB  - Expression of the proendocrine factor Neurogenin3 determines which progenitor
      cells in the developing pancreas will differentiate into the endocrine cells of
      the islets of Langerhans. To better understand how Neurogenin3 directs endocrine
      differentiation, we examined the mechanisms by which Neurogenin3 regulates the
      promoters of three transcription factor genes expressed in endocrine precursor
      cells: the nkx2.2 gene, the PAX4 gene, and the NEUROG3 gene, the human gene
      encoding Neurogenin3 itself. The function of all three promoters depends on at
      least one critical E box, a common DNA sequence that forms a binding site for
      basic helix-loop-helix proteins like Neurogenin3. Neurogenin3 bound to and
      effectively activated transcription through the nkx2.2 and PAX4 E boxes. In
      contrast, Neurogenin3 strongly repressed the NEUROG3 promoter, although a
      proximal E box was required for activity in the absence of Neurogenin3,
      suggesting that a ubiquitous transcriptional activator may bind to this site, and
      that Neurogenin3 could act as a competitive inhibitor of this activator. This
      hypothesis was supported by the lack of evidence for significant intrinsic
      transcriptional repression capacity in the Neurogenin3 protein, and by the
      ability of isolated DNA-binding basic helix-loop-helix domains to repress the
      NEUROG3 promoter. Neurogenin3 produced additional repression, however, when the
      protein included an intact transcriptional activation domain, suggesting that it
      may also induce the expression of a downstream transcriptional repressor. In
      summary, while Neurogenin3 orchestrates islet cell differentiation by activating
      islet cell transcription factor genes, it simultaneously represses its own
      promoter.

PMID- 14576337
TI  - Androgen receptor corepressor-19 kDa (ARR19), a leucine-rich protein that
      represses the transcriptional activity of androgen receptor through recruitment
      of histone deacetylase.
AB  - Androgen receptor (AR) that mediates androgen action is a crucial factor in male
      reproductive functions. Here, we report a novel AR corepressor ARR19 (androgen
      receptor corepressor-19 kDa), which has been isolated as a putative androgen
      induced gene from murine testis. ARR19 encoding a leucine-rich protein is
      expressed only in male reproductive organs such as testis and prostate. ARR19
      expression in the testis is developmentally regulated. Functional analysis
      conducted by the transient transfection of mammalian cells shows that ARR19
      represses AR transactivation in a dose-dependent manner. Furthermore, yeast two
      hybrid and glutathione S-transferase pull-down analyses reveal that ARR19
      directly associates with AR through the N-terminal and leucine zipper-containing
      regions of ARR19 and the DNA binding-hinge domain of AR. Interestingly, ARR19
      localized in the cytoplasmic compartment cotranslocates into the nucleus with AR
      upon androgen exposure. The ARR19 repression of AR transactivation is through the
      recruitment of histone deacetylase 4 (HDAC4) by ARR19. Overexpression of HDAC4
      further inhibits the ARR19-repressed AR transactivation. In addition, ARR19
      directly interacts with HDAC4 in vitro. Furthermore, DNA-protein complex
      immunoprecipitation assays reveal that HDAC4 is recruited to an androgen
      regulated promoter through ARR19. Taken together, the results suggest that ARR19
      may act as an AR corepressor in vivo and play an important role in male
      reproductive functions.

PMID- 14576338
TI  - Membrane restraint of estrogen receptor alpha enhances estrogen-dependent nuclear
      localization and genomic function.
AB  - Estrogen receptor (ER) alpha localizes to both the nucleus and the plasma
      membrane, mediating estrogen-dependent genomic and nongenomic signaling,
      respectively. In some cells, ERalpha appears to be excluded from the nucleus, and
      it is unclear whether genomic signaling takes place. The purpose of this study
      was to determine whether membrane-associated ERalpha is capable of genomic
      signaling, or whether this pool of receptors strictly serves membrane-mediated
      signaling. ERalpha fused to the C-terminal cytoplasmic tail of bovine rhodopsin
      (Rh-ERalpha) activates ER response element-dependent transcription only in the
      presence of estrogen; the activity is antagonized by the estrogen antagonist ICI
      182,780 and by the dominant-negative mutant of ERalpha and is unaffected by
      inhibitors of MAPKs and Akt signaling, indicating that this was due to direct
      genomic action. The activity of Rh-ERalpha containing the activating Y537S
      mutation was also estrogen dependent, suggesting that estrogen gated the entry of
      Rh-ERalpha into the nucleus. Indeed, cell fractionation studies demonstrated that
      Rh-ERalpha protein, in contrast to ERalpha that was nuclear at baseline, was
      excluded from the nucleus in the absence of hormone, and localized to the inner
      nuclear membrane on incubation with estrogen. These data demonstrate that
      membrane tethered ERalpha is capable of nuclear function and that its
      transcriptional activity is regulated by hormone-dependent entry into the inner
      nuclear membrane. Furthermore, these experiments provide evidence that under
      certain circumstances, membrane proteins are capable of nuclear function without
      detectable nucleoplasmic localization.

PMID- 14576339
TI  - Androgens promote maturation and signaling in mouse oocytes independent of
      transcription: a release of inhibition model for mammalian oocyte meiosis.
AB  - Normal fertility in females depends upon precise regulation of oocyte meiosis.
      Oocytes are arrested in prophase I of meiosis until just before ovulation, when
      meiosis, or maturation, is triggered to resume. Whereas sex steroids appear to
      promote maturation in fish and amphibians, the factors regulating mammalian
      oocyte maturation have remained obscure. We show here that, similar to lower
      vertebrates, steroids may play a role in promoting the release of meiotic
      inhibition in mammals. Specifically, testosterone induced maturation of mouse
      oocytes arrested in meiosis, as well as activation of MAPK and cyclin-dependent
      kinase 1 signaling. These responses appeared to be transcription independent and
      might involve signaling through classical androgen receptors expressed in the
      oocytes. Our results are the first to show that sex steroids can modulate meiosis
      in mammalian oocytes and suggest a model whereby dominant ovarian follicles in
      mammals may produce sufficient androgen and/or other steroids to overcome
      constitutive inhibitory signals and allow oocyte maturation and subsequent
      ovulation to occur.

PMID- 14576340
TI  - Pharmacological and physiological functions of the polyspecific organic cation
      transporters: OCT1, 2, and 3 (SLC22A1-3).
AB  - For the elimination of environmental toxins and metabolic waste products, the
      body is equipped with a range of broad-specificity transporters that are
      generally present in the liver, kidney, and intestine. The polyspecific organic
      cation transporters OCT1, 2, and 3 (SLC22A1-3) mediate the facilitated transport
      of a variety of structurally diverse organic cations, including many drugs,
      toxins, and endogenous compounds. OCT1 and OCT2 are found in the basolateral
      membrane of hepatocytes, enterocytes, and renal proximal tubular cells. OCT3 has
      a more widespread tissue distribution and is considered to be the major component
      of the extraneuronal monoamine transport system (or uptake-2), which is
      responsible for the peripheral elimination of monoamine neurotransmitters.
      Studies with knockout mouse models have directly demonstrated that these
      transporters can have a major impact on the pharmacological behavior of various
      substrate organic cations. The recent identification of polymorphic genetic
      variants of human OCT1 and OCT2 that severely affect transport activity thus
      suggests that some of the interpatient differences in response and sensitivity to
      cationic drugs may be caused by variable activity of these transporters.

PMID- 14576341
TI  - Gap junctions - from cell to molecule.

PMID- 14576342
TI  - Nongenic transcription, gene regulation and action at a distance.
AB  - In eukaryotes, motifs such as silencers, enhancers and locus control regions act
      over thousands of base pairs to regulate adjacent genes; insulators limit such
      effects, and barriers confine repressive heterochromatin to particular
      chromosomal segments. Recent results show that many of these motifs are nongenic
      transcription units, and two of them directly contact their targets lying further
      down the chromosome to loop the intervening DNA: the barriers (scs and scs')
      flanking the 87A7 heat-shock locus in the fly contact each other, and a locus
      control region touches the beta-globin gene in the mouse. I hypothesize that the
      act of transcription underlies the function of these regulators; active
      polymerizing complexes tend to cluster into 'factories' and this facilitates
      molecular contact between the transcribed regulator and its distant (and
      transcribed) target.

PMID- 14576343
TI  - Bcl-2 on the endoplasmic reticulum: protecting the mitochondria from a distance.
AB  - Bcl-2 has been described both as an inhibitor of programmed cell death and as an
      inhibitor of mitochondrial dysfunction during apoptosis. It is still not clear
      what biochemical activity of Bcl-2 is responsible for its function, but
      increasing evidence indicates that a functional activity of Bcl-2 on the
      endoplasmic reticulum (ER) protects mitochondria under diverse circumstances.
      Indeed, an emerging hypothesis is that, during apoptosis, the Bcl-2 family
      regulates ER-to-mitochondrion communication by BH3-only proteins and calcium ions
      and thereby triggers mitochondrial dysfunction and cell death.

PMID- 14576344
TI  - Cytoplasmic dynein in fungi: insights from nuclear migration.
AB  - Cytoplasmic dynein is a microtubule motor that mediates various biological
      processes, including nuclear migration and organelle transport, by moving on
      microtubules while associated with various cellular structures. The association
      of dynein with cellular structures and the activation of its motility are crucial
      steps in dynein-dependent processes. However, the mechanisms involved remain
      largely unknown. In fungi, dynein is required for nuclear migration. In budding
      yeast, nuclear migration is driven by the interaction of astral microtubules with
      the cell cortex; the interaction is mediated by dynein that is probably
      associated with the cortex. Recent studies suggest that budding yeast dynein is
      first recruited to microtubules, then delivered to the cortex by microtubules and
      finally activated by association with the cortex. Nuclear migration in many other
      fungi is probably driven by a similar mechanism. Recruitment of dynein to
      microtubules and its subsequent activation upon association with cellular
      structures are perhaps common to many dynein-dependent eukaryotic processes,
      including organelle transport.

PMID- 14576345
TI  - Migrating fibroblasts perform polarized, microtubule-dependent exocytosis towards
      the leading edge.
AB  - Cell migration might involve biased membrane traffic toward the leading edge to
      facilitate the building of extracellular matrix, membrane protrusions and
      adhesion plaques. We tested the hypothesis that secretory vesicles are
      preferentially delivered toward the leading lamella in wound-edge fibroblasts.
      Single fusion events of vesicles containing LDLR-GFP were mapped by total
      internal reflection fluorescence microscopy (TIR-FM). In migrating fibroblasts,
      exocytic events were polarized towards the leading edge. After disrupting
      microtubules with nocodazole, exocytosis continued, but fusion sites were
      clustered around central Golgi elements; there was no peripheral exocytosis. We
      conclude that microtubules are necessary for the domain-specific fusion of post
      Golgi vesicles with the plasma membrane during migration.

PMID- 14576346
TI  - The Chironomus tentans translation initiation factor eIF4H is present in the
      nucleus but does not bind to mRNA until the mRNA reaches the cytoplasmic
      perinuclear region.
AB  - In the cell nucleus, precursors to mRNA, pre-mRNAs, associate with a large number
      of proteins and are processed to mRNA-protein complexes, mRNPs. The mRNPs are
      then exported to the cytoplasm and the mRNAs are translated into proteins. The
      mRNAs containing in-frame premature stop codons are recognized and degraded in
      the nonsense-mediated mRNA decay process. This mRNA surveillence may also occur
      in the nucleus and presumably involves components of the translation machinery.
      Several translation factors have been detected in the nucleus, but their
      functional relationship to the dynamic protein composition of pre-mRNPs and mRNPs
      in the nucleus is still unclear. Here, we have identified and characterized the
      translation initiation factor eIF4H in the dipteran Chironomus tentans. In the
      cytoplasm, Ct-eIF4H is associated with poly(A+) RNA in polysomes. We show that a
      minor fraction of Ct-eIF4H enters the nucleus. This fraction is independent on
      the level of transcription. CteIF4H could not be detected in gene-specific pre
      mRNPs or mRNPs, nor in bulk mRNPs in the nucleus. Our immunoelectron microscopy
      data suggest that Ct-eIF4H associates with mRNP in the cytoplasmic perinuclear
      region, immediately as the mRNP exits from the nuclear pore complex.

PMID- 14576347
TI  - The 5T4 oncofoetal antigen is an early differentiation marker of mouse ES cells
      and its absence is a useful means to assess pluripotency.
AB  - 5T4 oncotrophoblast antigen is a transmembrane glycoprotein expressed by
      trophoblast and many carcinomas but not most normal adult tissues. Results from
      overexpression of human and mouse 5T4 cDNA in cell lines are consistent with it
      having an influence on adhesion, shape and motility. We show that murine
      embryonic stem cell lines are 5T4 negative but that there is rapid up regulation
      of protein and transcripts upon differentiation, including derivatives of each
      primary germ layer, as evidenced by cell surface FACS, western and RT-PCR
      analyses. The kinetics of differentiation and 5T4 expression are closely
      correlated, with early events linking 5T4 expression to changes in motility and
      morphology. Comparison of 5T4 expression with other ES cell transcript (Oct 3/4;
      Rex-1) and antigen markers (Forsmann, SSEA-1) establishes 5T4 as a useful marker
      for the non-destructive detection of early differentiation of ES cells. For
      example, 'undifferentiated' ES phenotype defined as SSEA-1 positive and 5T4
      negative is seven times more efficient at chimera formation than SSEA-1
      positive/5T4-positive cells. Thus, 5T4 glycoprotein expression is associated with
      early differentiative events of ES cells involving altered motility, and it has
      useful practical consequences for assessing ES potency and studying similar
      processes in development and metastasis.

PMID- 14576348
TI  - Bpag1 localization to actin filaments and to the nucleus is regulated by its N
      terminus.
AB  - Plakins are a family of giant cytoskeleton binding proteins. One member of this
      group is bullous pemphigoid antigen 1 (Bpag1)/dystonin, which has neuronal and
      muscle isoforms that consist of actin-binding and microtubule-binding domains at
      either end separated by a plakin domain and several spectrin repeats. The better
      characterized epithelial isoform has only the plakin domain in common with the
      neuronal and muscle isoforms. Here, we have analyzed the localization of
      muscle/neuronal (Bpag1a/b) isoforms and the epithelial (Bpag1e) isoform within
      C2C12 myoblast cells. Although an antibody specific to Bpag1a/b isoform 2
      detected protein co-aligning actin stress fibers, this same antibody and two
      Bpag1e antibodies predominantly detected protein in the nuclei. A Bpag1a/b
      isoform 2 N-terminal fusion protein containing the plakin domain also localized
      to actin stress fibers and to nuclei. Within the plakin domain, we characterized
      a functional nuclear localization signal, which was responsible for localization
      of the fusion protein to the nucleus. Bpag1a/b isoform 1 N-terminal fusion
      proteins differed in their interaction with the actin cytoskeleton and with their
      ability to localize to the nucleus, suggesting that Bpag1 isoforms with different
      N-termini have differing roles. These results show the importance of N-terminal
      domains in dictating the localization and function of Bpag1 isoforms. We provide
      the first indication that Bpag1 is not strictly a cytoplasmic/membrane protein
      but that it can also localize to the nucleus.

PMID- 14576349
TI  - Tetraspanin CD82 regulates compartmentalisation and ligand-induced dimerization
      of EGFR.
AB  - We have previously shown that CD82, a transmembrane protein of the tetraspanin
      superfamily is associated with EGFR and has a negative effect on EGF-induced
      signalling (Odintsova, E., Sugiura, T. and Berditchevski, F. (2000) Curr. Biol.
      10, 1009-1012). Here we demonstrate that CD82 specifically attenuates ligand
      induced dimerization of EGFR. The recombinant soluble large extracellular loop of
      CD82 has no effect on the dimerization thereby suggesting that other parts of the
      protein are required. Although CD82 is also associated with ErbB2 and ErbB3,
      ligand-induced assembly of the ErbB2-ErbB3 complexes is not affected in CD82
      expressing cells. Furthermore, in contrast to the CD82-EGFR association, CD82
      ErbB2 and CD82-ErbB3 complexes are stable in the presence of ErbB3 ligand. The
      effect of CD82 on the formation of EGFR dimers correlates with changes in
      compartmentalisation of the ErbB receptors on the plasma membrane. Expression of
      CD82 causes a significant increase in the amount of EGFR and ErbB2 in the light
      fractions of the sucrose gradient. This correlates with the increased surface
      expression of gangliosides GD1a and GM1 and redistribution of GD1a and EGFR on
      the plasma membrane. Furthermore, in CD82-expressing cells GD1a is co-localised
      with EGFR and the tetraspanin. Taken together our results offer a molecular
      mechanism of the attenuating activity of CD82 towards EGFR, whereby GD1a
      functions as a mediator of CD82-dependent compartmentalisation of the receptor.

PMID- 14576350
TI  - Fhos, a mammalian formin, directly binds to F-actin via a region N-terminal to
      the FH1 domain and forms a homotypic complex via the FH2 domain to promote actin
      fiber formation.
AB  - Formins constitute a family of eukaryotic proteins that are considered to
      function as a cytoskeleton organizer to regulate morphogenesis, cell polarity and
      cytokinesis. Fhos is a recently identified mammalian formin, which contains the
      conserved domains FH (formin homology) 1 and FH2 in the middle region and the Dia
      autoregulatory domain (DAD) in the C-terminus. The role of Fhos in the regulation
      of cytoskeleton, however, has remained unknown. Here we show that Fhos, in an
      active form, induces the formation of actin stress fibers and localizes to the
      actin-based structure. Fhos appears to normally exist in a closed inactive form
      via an intramolecular interaction between the N-terminal region and the C
      terminal DAD. Both FH1 and FH2 domains are required for the induction of the
      stress fiber formation. However, the N-terminal region of Fhos is required for
      the targeting of this protein to stress fibers, which is probably mediated via
      its F-actin-binding activity. We also show that Fhos occurs as a homotypic
      complex in cells. The self-association of Fhos seems to be mediated via the FH2
      domain: the domains bind to each other in a direct manner. Thus, the mammalian
      formin Fhos, which directly binds to F-actin via the N-terminal region, forms a
      homotypic complex via the FH2 domain to organize actin cytoskeleton.

PMID- 14576351
TI  - Direct translocation of histone molecules across cell membranes.
AB  - The present work shows that histones are able to directly cross cell plasma
      membranes and mediate penetration of macromolecules covalently attached to them.
      Adding a mixture containing the five nucleosomal histones, H1, H2A, H2B, H3 and
      H4, as well as each of the last four individual histones to intact HeLa and Colo
      205 cultured cells resulted in cell penetration and nuclear import of these
      externally added histones. This was observed by fluorescent and confocal
      microscopy using fixed and unfixed cells, showing that penetration was not due to
      the fixation process. Accumulation was also estimated by a quantitative assay
      that did not require cell fixation and allowed neutralization of surface-bound
      histones. Translocation into the HeLa and Colo-205 cells occurred at 4 degrees C,
      in ATP-depleted cells and in cells incubated with sucrose (0.5 M) - conditions
      that block the endocytic pathway. Furthermore, various endocytosis inhibitors
      such as colchicine, nocodazole, cytochalasin D, brefeldin A, chloroquine and
      nystatin did not have any effect on the penetration process. Thus, cellular
      uptake was mostly due to direct translocation of the histones through the cell
      plasma membrane and not to endocytosis. The histones were also able to mediate
      penetration of covalently attached bovine serum albumin (BSA) molecules,
      indicating their potential as carriers for the delivery of macromolecules into
      living mammalian cells.

PMID- 14576352
TI  - Defective endochondral ossification in mice with strongly compromised expression
      of JunB.
AB  - Functional analysis in mice has established an absolute requirement of JunB, a
      member of the AP-1 transcription factor family, during early embryonic
      development. To investigate the role of JunB during mid and late gestation and
      postnatally Ubi-junB transgenic mice were used to generate two junB-/- Ubi-junB
      mutant lines, in which embryonic lethality was rescued but strongly reduced JunB
      expression in several adult tissues was observed. Mutant mice from both rescue
      lines were growth retarded and shared significantly reduced longitudinal bone
      growth. Mutant long bones were characterised by reduced numbers of growth plate
      chondrocytes and a severe osteoporosis. Decreased JunB levels in epiphysal growth
      plate chondrocytes and bone lining osteoblasts correlated with deregulated
      expression of Cyclin A, Cyclin D1 and p16INK4a, key regulators of cell cycle
      control. Furthermore, junB-/- Ubi-junB bone marrow stromal cells were unable to
      differentiate into bone forming osteoblasts in vitro. Our data demonstrate that
      JunB plays a crucial role in endochondral ossification by regulating
      proliferation and function of chondrocytes and osteoblasts.

PMID- 14576353
TI  - DIAP1 suppresses ROS-induced apoptosis caused by impairment of the selD/sps1
      homolog in Drosophila.
AB  - The cellular antioxidant defense systems neutralize the cytotoxic by-products
      referred to as reactive oxygen species (ROS). Among them, selenoproteins have
      important antioxidant and detoxification functions. The interference in
      selenoprotein biosynthesis results in accumulation of ROS and consequently in a
      toxic intracellular environment. The resulting ROS imbalance can trigger
      apoptosis to eliminate the deleterious cells. In Drosophila, a null mutation in
      the selD gene (homologous to the human selenophosphate synthetase type 1) causes
      an impairment of selenoprotein biosynthesis, a ROS burst and lethality. We
      propose this mutation (known as selDptuf) as a tool to understand the link
      between ROS accumulation and cell death. To this aim we have analyzed the
      mechanism by which selDptuf mutant cells become apoptotic in Drosophila imaginal
      discs. The apoptotic effect of selDptuf does not require the activity of the
      Ras/MAPK-dependent proapoptotic gene hid, but results in stabilization of the
      tumor suppressor protein Dmp53 and transcription of the Drosophila pro-apoptotic
      gene reaper (rpr). We also provide genetic evidence that the initiator caspase
      DRONC is activated and that the effector caspase DRICE is processed to commit
      selDptuf mutant cells to death. Moreover, the ectopic expression of the inhibitor
      of apoptosis DIAP1 rescues the cellular viability of selDptuf mutant cells. These
      observations indicate that selDptuf ROS-induced apoptosis in Drosophila is mainly
      driven by the caspase-dependent Dmp53/Rpr pathway.

PMID- 14576354
TI  - Early molecular events in the assembly of matrix adhesions at the leading edge of
      migrating cells.
AB  - Cellular locomotion is driven by repeated cycles of protrusion of the leading
      edge, formation of new matrix adhesions and retraction of the trailing edge. In
      this study we addressed the molecular composition and dynamics of focal
      complexes, formed under the leading lamellae of motile cells, and their
      maturation into focal adhesions. We combined phase-contrast and fluorescence
      microscopy approaches to monitor the incorporation of phosphotyrosine and nine
      different focal adhesion proteins into focal complexes in endothelial cells,
      migrating into an in vitro 'wound'. We show that newly formed complexes are
      located posterior to an actin-, VASP- and alpha-actinin-rich region in the
      lammelipodium. They are highly tyrosine phosphorylated, contain beta3-integrin,
      talin, paxillin and low levels of vinculin and FAK, but are apparently devoid of
      zyxin and tensin. The recruitment of these proteins into focal complexes occurs
      sequentially, so that their specific protein composition depends on their age.
      Interestingly, double color, time-lapse movies visualizing both paxillin and
      zyxin, indicated that the transition from paxillin-rich focal complexes to
      definitive, zyxin-containing focal adhesions, takes place only after the leading
      edge stops advancing or retracts. These observations illuminate, for the first
      time, early stages in focal complex assembly and the dynamic process associated
      with its transformation into focal adhesion.

PMID- 14576355
TI  - Potential role of MCP-1 in endothelial cell tight junction 'opening': signaling
      via Rho and Rho kinase.
AB  - The expression of the monocyte chemoattractant protein-1 (MCP-1) receptor CCR2 by
      brain endothelial cells suggests that MCP-1 may have other functions than purely
      driving leukocyte migration into brain parenchyma during inflammation. This study
      examines one of these potential novel roles of MCP-1 regulation of endothelial
      permeability using primary cultures of mouse brain endothelial cells. MCP-1
      induces reorganization of actin cytoskeleton (stress fiber formation) and
      redistribution of tight junction proteins, ZO-1, ZO-2 occludin and claudin-5,
      from the Triton X-100-soluble to the Triton X-100-insoluble fractions. These
      morphological changes are associated with a decrease in transendothelial
      electrical membrane resistance and an increase in [14C]inulin permeability. MCP-1
      did not induce these events in brain endothelial cells prepared from mice
      genotype CCR2-/-. The Rho kinase inhibitor Y27632 and inhibition of Rho (C3
      exoenzyme, and dominant negative mutant of Rho, RhoT19N) prevented MCP-1-induced
      stress fiber assembly, reorganization of tight junction proteins and alterations
      in endothelial permeability. In all, this suggests that a small GTPase Rho and
      Rho kinase have a pivotal role in MCP-1-induced junction disarrangement. These
      data are the first to strongly suggest that MCP-1, via CCR2 present on brain
      endothelial cells, contributes to increased brain endothelial permeability.

PMID- 14576356
TI  - Keratin-8 null mice have different gallbladder and liver susceptibility to
      lithogenic diet-induced injury.
AB  - Keratin transgenic mouse models and the association of human keratin mutations
      with liver disease highlight the importance of keratins in protecting the liver
      from environmental insults, but little is known regarding keratins and their
      function in the gallbladder. We characterized keratin expression pattern and
      filament organization in normal and keratin polypeptide-8 (K8)-null, K18-null and
      K19-null gallbladders, and examined susceptibility to liver and gallbladder
      injury induced by a high-fat lithogenic diet (LD) in K8-null mice. The major
      keratins of normal mouse gallbladder are K8>K19>K18 which become markedly
      depleted in K8-null mice with minor K18/K19 remnants and limited K7 over
      expression. Compensatory K18/K20 protein and RNA overexpression occur in K19-null
      but not in K18-null gallbladders, probably because of the higher levels of K19
      than K18 in normal gallbladder. LD challenge causes more severe liver injury in
      K8-null than wild-type mice without altering keratin protein levels. In contrast,
      wild-type and K8-null gallbladders are equally susceptible to LD-induced injury
      and stone formation, but wild-type gallbladders do overexpress keratins upon LD
      challenge. LD-induced injury triggers keratin hyperphosphorylation in wild-type
      livers and gallbladders. Hence, mouse gallbladder K8/K18/K19 expression is
      induced in response to cholelithiasis injury. A high-fat LD increases the
      susceptibility of K8-null mice to liver but not gallbladder injury, which
      suggests that keratin mutations may increase the risk of liver damage in patients
      with steatohepatitis. Differences between K8-null mouse gallbladder and
      hepatocyte susceptibility to injury may be related to their minimal versus absent
      keratin expression, respectively.

PMID- 14576357
TI  - Myosin Va and microtubule-based motors are required for fast axonal retrograde
      transport of tetanus toxin in motor neurons.
AB  - Using a novel assay based on the sorting and transport of a fluorescent fragment
      of tetanus toxin, we have investigated the cytoskeletal and motor requirements of
      axonal retrograde transport in living mammalian motor neurons. This essential
      process ensures the movement of neurotrophins and organelles from the periphery
      to the cell body and is crucial for neuronal survival. Unlike what is observed in
      sympathetic neurons, fast retrograde transport in motor neurons requires not only
      intact microtubules, but also actin microfilaments. Here, we show that the
      movement of tetanus toxin-containing carriers relies on the nonredundant
      activities of dynein as well as kinesin family members. Quantitative kinetic
      analysis indicates a role for dynein as the main motor of these carriers.
      Moreover, this approach suggests the involvement of myosin(s) in retrograde
      movement. Immunofluorescence screening with isoform-specific myosin antibodies
      reveals colocalization of tetanus toxin-containing retrograde carriers with
      myosin Va. Motor neurons from homozygous myosin Va null mice showed slower
      retrograde transport compared with wild-type cells, establishing a unique role
      for myosin Va in this process. On the basis of our findings, we propose that
      coordination of myosin Va and microtubule-dependent motors is required for fast
      axonal retrograde transport in motor neurons.

PMID- 14576358
TI  - Control of embryonic Xenopus morphogenesis by a Ral-GDS/Xral branch of the Ras
      signalling pathway.
AB  - Ras proteins mediate biological responses through various effectors and play a
      key role in relaying the Fibroblast Growth Factor (FGF) mesoderm induction signal
      during embryogenesis of the frog, Xenopus laevis. One Ras effector pathway
      involves the activation of the small G protein Ral. In the present study, we have
      investigated the role of key components in the Ral branch of FGF and Ras
      signalling during early Xenopus development. Treatment of animal caps with bFGF,
      which converts prospective ectoderm to mesoderm, activates Xral. The Ras mutant
      12V37G, which can bind to Ral-GDS but not Raf, also activates Xral as well as
      causing developmental defects and cortical F-actin disassembly. A similar
      phenotype is induced by Ral-GDS itself. FGF-induced expression of several
      signature mesodermal genes, by contrast, is independent of Xral signalling. This
      and other data suggest that the RalB branch of Ras and FGF signalling regulates
      the actin cytoskeleton and morphogenesis in a transcriptionally independent
      manner. We also find Xral to be specifically activated in the marginal zone of
      Xenopus embryos, and find that disruption of the Ral pathway in this region
      prevents closure of the blastopore during gastrulation. We conclude that Ral
      signalling is autonomously required by mesodermal cells to effect essential
      morphogenetic changes during Xenopus gastrulation.

PMID- 14576359
TI  - Stimulation of extracellular matrix remodeling by the first type III repeat in
      fibronectin.
AB  - The fibronectin matrix contains cryptic sites which are thought to modulate
      cellular biological responses. One of these sites, located in fibronectin's first
      type III repeat (III1c), influences signaling pathways that are relevant to
      cytoskeletal organization and cell cycle progression. The purpose of this study
      was to identify possible mechanisms responsible for the effects of III1c on cell
      behavior. Recombinant peptides representing various type III repeats of
      fibronectin were compared for their effects on fibronectin matrix organization
      and activation of intracellular signaling pathways. III1c and III13 but not
      III11c or III10 bound to monolayers of human skin fibroblasts in a dose- and time
      dependent manner and were localized to the extracellular matrix. Binding of
      III13, but not III1c, to matrix was sensitive to heparitinase, suggesting that
      the association of III1c with the matrix was not dependent on heparan sulfate
      proteoglycans. Quantitative and morphological assessment indicated that, in
      contrast to previously published reports, the binding of III1c to cell layers did
      not result in the loss or disruption of matrix fibronectin. Binding of III1c but
      not III13 to the extracellular matrix did result in the loss of a
      conformationally sensitive epitope present within the EDA type III module of
      cellular fibronectin. III1c-induced loss of the EDA epitope did not require the
      presence of cells, occurred within 1 hour and was associated with the activation
      of p38 mitogen-activated protein kinase (MAPK) followed by the formation of
      filopodia. Maximal phosphorylation of p38 MAPK occurred within 1 hour, whereas
      cytoskeletal changes did not appear until 12 hours later. These findings are
      consistent with a model in which the binding of III1c to the extracellular matrix
      results in a conformational remodeling of the fibronectin matrix, which has both
      short- and long-term effects on cell physiology.

PMID- 14576360
TI  - Mutation of an unusual mitochondrial targeting sequence of SODB2 produces
      multiple targeting fates in Toxoplasma gondii.
AB  - Proteins destined for the mitochondria travel an intricate pathway through two
      membranes, each with its own receptors and channels. These proteins interact with
      receptors via N-terminal presequences that form amphipathic helices. Generally,
      these helices contain abundant positive charges on one face and hydrophobic
      residues on the other, but share little primary sequence homology. While
      extensive research on mitochondrial import has been done in yeast and mammalian
      cells, little is known about import or contents of the single mitochondrion of
      Toxoplasma gondii, a parasite in the phylum Apicomplexa. We describe here the
      characterization of TgSODB2, a novel, mitochondrial superoxide dismutase in T.
      gondii with an unusual targeting sequence consisting of a hydrophobic segment
      resembling a signal peptide, followed by a presequence. We show that although the
      hydrophobic segment is competent to target a reporter protein to the secretory
      system, it is prevented from directing ER translocation when coupled with the
      presequence. When we mutated the only charged residue in the hydrophobic
      sequence, ER translocation is restored and the reporter targeted to the
      apicoplast, a chloroplast-like organelle found in most apicomplexans. The
      presequence that follows is predicted to form an amphipathic helix, but targeted
      the cytoplasm when the hydrophobic peptide is removed. In addition to having an
      unusual targeting sequence, TgSODB2 is only the second mitochondrially imported,
      iron-containing SOD to be described.

PMID- 14576361
TI  - Aggregation of beta2 integrins activates human neutrophils through the IkappaB/NF
      kappaB pathway.
AB  - Neutrophils are now considered central to the pathogenesis of most forms of acute
      lung injury. Neutrophils do not cause damage while suspended in the bloodstream;
      however, a release of cytotoxic agents occurs when neutrophils are adherent to
      endothelium, epithelium, or extracellular matrix proteins in the interstitium.
      Such neutrophil adherence is mediated predominantly through beta(2) integrins
      (CD11/CD18) on its surface. This study was undertaken to investigate whether the
      IkappaB/nuclear factor (NF)-kappaB cascade is involved in this beta(2) integrin
      mediated activation of human neutrophils. beta(2) Integrin Mac-1 (CD11b/CD18)
      aggregation was induced by antibody cross-linking of the integrins on the cell
      surface. beta(2) Integrin aggregation induced interleukin-1beta and tumor
      necrosis factor-alpha production, which suggests the activation of neutrophils by
      beta(2) integrin. IkappaBalpha was markedly degraded at 1 h, and NF-kappaB-DNA
      binding activity markedly increased 2 h after beta(2) integrin aggregation, which
      activated IkappaB kinase activity at 1 h. beta(2) Integrin-induced cytokine
      production was suppressed by MG132 or SN50 pretreatment, which blocked the
      activation of NF-kappaB. These findings suggest that the activation of human
      neutrophils by beta(2) integrin aggregation is mediated through the activation of
      the IkappaB/NF-kappaB pathway.

PMID- 14576362
TI  - Phenotypic and functional alterations of peripheral blood monocytes in neutrophil
      specific granule deficiency.
AB  - Neutrophil-specific granule deficiency (SGD) is a rare, congenital disease
      characterized by atypical neutrophil structure and function, resulting in
      recurrent bacterial infections from early infancy. Homozygous recessive mutations
      in the CCAAT/enhancer-binding protein epsilon (C/EBPepsilon) gene were described
      in two of five SGD patients, indicating loss of C/EBPepsilon function as the
      primary genetic defect in this disease. C/EBPepsilon is expressed in murine and
      human macrophages. Macrophages from the C/EBPepsilon-deficient mice show impaired
      differentiation, phagocytic activity, and transcription of macrophage-specific
      genes. To determine if monocyte/macrophage cells are impacted in SGD, we analyzed
      phenotypic features of peripheral blood (PB) monocytes in a SGD individual
      lacking functional C/EBPepsilon. Flow cytometric analysis of PB leukocytes
      revealed aberrant expression of CD45, CD11b, CD14, CD15, and CD16 on cells from
      the SGD individual. Also, the PB CD14(+) cells from this individual, weakly
      stained for the monocyte-specific enzyme, nonspecific esterase, and electron
      microscopic examination, indicated morphologic differences between the SGD cells
      and those from normal controls. Serum interleukin (IL)-6 levels in the SGD
      individual during a severe bacterial infection were lower compared with levels in
      other non-SGD individuals with sepsis. In contrast, serum IL-8 levels were
      markedly elevated in the SGD individual compared with those of non-SGD
      individuals in sepsis. PB CD14(+) cells from the SGD individual expressed higher
      IL-8 mRNA levels compared with normal controls in response to lipopolysaccharide
      and interferon-gamma. These phenotypic and functional alterations of PB monocytes
      in the SGD individual suggest that C/EBPepsilon plays a critical role in
      monocyte/macrophage development of humans and is consistent with observations in
      the murine system. This study implicates abnormalities in monocytes/macrophages
      and neutrophils in the onset and development of SGD.

PMID- 14576363
TI  - Autocrine inhibitory influences of alpha-melanocyte-stimulating hormone in
      malignant pleural mesothelioma.
AB  - Malignant pleural mesothelioma is a highly aggressive tumor arising from the
      mesothelial cells that line the pleural cavities. This tumor is resistant to most
      conventional anticancer treatments and appears to be very sensitive to growth
      promoting influences of cytokines and growth factors. Identification of natural
      inhibitory pathways that control growth should aid discovery of novel therapeutic
      approaches. We hypothesized that alpha-melanocyte-stimulating hormone (alpha
      MSH), which is produced by many cell types and antagonizes cytokines and growth
      factors, could be an endogenous inhibitory molecule in mesothelioma. Twelve
      mesothelioma cell lines were established from pleural effusions of patients with
      malignant mesothelioma. Mesothelioma cells were found to express mRNA for
      proopiomelanocortin and its processing enzymes; release alpha-MSH peptide into
      supernatants; and express melanocortin 1 receptor (MC1R), the high-affinity
      receptor for alpha-MSH. Immunoneutralization of MC1R in the cell lines enhanced
      expression of interleukin-8 (IL-8), IL-6, and transforming growth factor-beta.
      These molecules promote mesothelioma proliferation and are considered therapeutic
      targets in this tumor. Coincubation of mesothelioma cells with synthetic alpha
      MSH significantly reduced cell proliferation. The present research shows an
      autocrine-inhibitory circuit based on alpha-MSH and its receptor MC1R. Activation
      of MC1R by selective peptides or peptidomimetics might provide a novel strategy
      to reduce mesothelioma cell proliferation by taking advantage of this endogenous
      inhibitory circuit.

PMID- 14576364
TI  - Autologous stem-cell transplantation restores the functional properties of
      CD14+CD16+ monocytes in patients with myeloma and lymphoma.
AB  - The CD14+CD16+ monocytes appear to be important to immune defense against
      infection, as these cells are very potent with respect to tumor necrosis factor
      (TNF) production, phagocytosis, and antigen presentation. Myeloablative high-dose
      chemotherapy (HDT) and subsequent autologous stem-cell transplantation (ASCT) are
      being used increasingly for therapy of hematological malignancies, but the
      pronounced immunosuppression renders the patients prone to infection. To
      determine the functional properties of CD14+CD16+ monocytes under these
      conditions, 15 patients with lymphoma or myeloma were examined. Before HDT, the
      ratio of CD14+CD16+ cells to the population of the classical CD14++ monocytes was
      0.28 +/- 0.12; this ratio changed during the course of HDT and ASCT in favor of
      the CD14+CD16+ monocytes to a maximum of 12.4 +/- 7.8 (P<0.001) on day 3.5 +/-
      1.6 after transplanation (Tx) and returned to 0.11 +/- 0.07 (P<0.001) after
      engraftment on day 11.3 +/- 2.2. Although the absolute number of classical CD14++
      monocytes declined to less than 1/microl at the nadir, the number of
      CD14+CD16+monocytes fell from 29.7 +/- 9.8/microl to 4.5 +/- 3.0/microl at the
      nadir and increased to 13.8 +/- 9.8/microl at the day of discharge from the
      hospital. Flow cytometric analysis of phagocytosis of fluorescein isothiocyanate
      (FITC)-labeled Escherichia coli showed that 30 +/- 10% CD14+CD16+ monocytes of
      patients were FITC-positive before Tx, and at engrafment, the percentage of FITC
      positive cells had doubled to 60 +/- 6% (healthy controls, 41+/-7%). When
      determining generation of reactive oxygen species after E. coli ingestion, the
      CD14+CD16+ monocytes showed a decreased response before Tx (32+/-12% positve
      cells), which increased to 53 +/- 24% after ASCT. The median fluorescence
      intensity of human leukocyte antigen (HLA)-DR expression on the CD14+CD16+
      monocytes increased from 11 +/- 6 before Tx to 17 +/- 11 after Tx, and the
      production of TNF after lipopolysaccharide showed no remarkable difference (46+/
      13 vs. 49+/-14 channels). At the same time, expression of TNF and of HLA-DR
      showed a dramatic decrease in the CD14++ monocytes. Taken together after stem
      cell Tx, the function of the CD14++ monocytes is impaired, and the functional
      properties of CD14+CD16+ monocytes recover, indicating that these cells may be
      important for defense against infections post-ASCT.

PMID- 14576365
TI  - Editorial comment--Early supported discharge: an idea whose time has come?

PMID- 14576366
TI  - Editorial comment--Utility of abciximab during carotid stenting when distal
      protection is contraindicated.

PMID- 14576367
TI  - Bone mineral density, blood pressure, and stroke in elderly women.

PMID- 14576368
TI  - PWI/DWI mismatch: better definition required.

PMID- 14576369
TI  - Effect of area-based deprivation on the severity, subtype, and outcome of
      ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Markers of low socioeconomic status (deprivation) are
      associated with stroke and its causes. In the United Kingdom, area-based
      deprivation measures are available routinely through links with postal codes. We
      hypothesized that deprivation is associated with ischemic stroke risk factors,
      severity, subtype, and outcome. METHODS: We studied 2026 patients, each with at
      least 2 years of outcome follow-up by record linkage after first admission with
      ischemic stroke to an acute stroke unit. Baseline factors recorded routinely were
      age, sex, medical history, blood pressure, and stroke severity and subtype.
      Deprivation was assessed by the Womersley score (WS) and Murray score (MS).
      RESULTS: Higher WS and MS were associated with stroke at younger age (eg, WS
      linear regression coefficient (r)=-0.26; 95% confidence interval [CI], -0.51 to 
      0.01 per additional point), smoking (odds ratio [OR], 1.12; 95% CI, 1.08 to
      1.17), and claudication (OR, 1.09; 95% CI, 1.01 to 1.17); WS was associated with
      higher systolic blood pressure (r=0.13; 95% CI, 0.02 to 0.24); and MS was
      associated with severe stroke. Deprivation was not associated with case fatality
      in univariate analysis or after correction for all baseline factors. Deprivation
      was associated with readmission to hospital as a result of any vascular event in
      univariate analysis (hazard ratio [HR], 1.05; 95% CI, 1.02 to 1.09) and after
      correction for all baseline factors (HR, 1.06; 95% CI, 1.02 to 1.10).
      CONCLUSIONS: Tackling health inequalities in stroke should focus on stroke
      primary prevention by tackling deprivation, including promoting changes in
      lifestyle.

PMID- 14576371
TI  - Editorial comment--Secondary prevention of stroke: beyond meta-analyses.

PMID- 14576370
TI  - Beyond mismatch: evolving paradigms in imaging the ischemic penumbra with
      multimodal magnetic resonance imaging.
AB  - BACKGROUND: The ability to quickly and efficiently identify the ischemic penumbra
      in the acute stroke clinical setting is an important goal for stroke researchers
      and clinicians. Early and accurate identification of potentially salvageable
      versus irreversibly infarcted brain tissue may enable selection of the most
      appropriate candidates for early stroke therapies and identify patients who may
      still benefit from late recanalization or neuroprotective treatment. Recent
      advances in magnetic resonance imaging of the ischemic penumbra have been driven
      by serial MRI studies characterizing the natural evolution of cerebral infarction
      as well as the brain's response to reperfusion. SUMMARY OF COMMENT: Based on
      these studies, various models for imaging the penumbra with MRI have been
      proposed, including the pioneering diffusion-perfusion mismatch model and later
      multivariate approaches. Each model has its own unique advantages and
      disadvantages. CONCLUSIONS: There now are sufficient data to support paradigm
      shifts in a variety of central tenets regarding MRI and the ischemic penumbra.
      These include the insights that diffusion-perfusion mismatch does not optimally
      define the penumbra; that early diffusion lesions are in part reversible and
      often include both irreversibly infarcted tissue and penumbra; that the visible
      zone of perfusion abnormality overestimates the penumbra by including regions of
      benign oligemia; that MRI is a very practical method for acute stroke imaging;
      and that therapeutic salvage of the ischemic penumbra has been demonstrated in
      humans using diffusion-perfusion MRI.

PMID- 14576372
TI  - Cyclooxygenase-2 inhibitors: are they really atherothrombotic, and if not, why
      not?
AB  - BACKGROUND AND SUMMARY: Selective cyclooxygenase (COX)-2 inhibitors are
      increasingly being used in place of "conventional" nonsteroidal anti-inflammatory
      drugs (NSAIDs). This is because they are just as effective as NSAIDs in relieving
      arthritic pain and yet less gastrotoxic. However, the cardiovascular safety of
      selective COX-2 inhibitors has been questioned because they selectively reduce
      prostacyclin production, thus disrupting the normal homeostatic balance and
      promoting a prothrombotic state. These theoretical concerns appear to be
      supported by the results of clinical trials demonstrating an increased risk of
      myocardial infarction with COX-2 inhibitors compared with a conventional NSAID,
      and indirect comparisons of the rates of myocardial infarction among patients
      treated with a selective COX-2 inhibitor compared with aspirin in different
      trials. However, emerging data from animal, experimental and clinical studies
      suggest that COX-2 is atherogenic and thrombogenic, and that selective COX-2
      inhibitors may be cardioprotective. Meta-analyses of randomized trials of
      selective COX-2 inhibitors compared with placebo have demonstrated no excess of
      cardiovascular events among patients allocated COX-2 inhibitors, and preliminary
      data from a randomized controlled trial of the selective COX-2 inhibitor
      meloxicam, in patients with acute coronary syndrome who were treated with
      aspirin, demonstrated a reduction in cardiovascular events among patients
      allocated the COX-2 inhibitor. CONCLUSIONS: Continuing uncertainty regarding the
      direction and magnitude of any cardiovascular effects of selective COX-2
      inhibitors, coupled with their widespread and increasing use, mandates
      prospective randomized evaluation of their efficacy and safety in patients at
      increased risk of future cardiovascular events.

PMID- 14576373
TI  - Endothelial nitric oxide synthase T-786C single nucleotide polymorphism: a
      putative genetic marker differentiating small versus large ruptured intracranial
      aneurysms.
AB  - BACKGROUND AND PURPOSE: Anecdotal evidence exists for at least 2 subpopulations
      of intracranial saccular aneurysms, namely, those that may form rapidly and
      rupture when small versus those that enlarge slowly and may rupture particularly
      when > or =10 mm in diameter. We sought to determine whether the endothelial
      nitric oxide synthase (eNOS) T-786C single nucleotide polymorphism (SNP),
      implicated in cardiovascular disease susceptibility, could facilitate
      differentiation between small (< or =5 mm) versus large (> or =10 mm) ruptured
      aneurysms. METHODS: In accordance with institutional guidelines, clinical data
      were recorded prospectively and genomic DNA was isolated from blood samples
      obtained from 52 aneurysmal subarachnoid hemorrhage (SAH) patients (cases) and 90
      randomly selected controls. Samples were assayed for eNOS gene promoter T-786C
      SNP with the use of gene microarray technology. Statistical analyses included
      multiple logistic regression. RESULTS: Although there was no difference in
      genotype distributions between cases and controls, all 13 patients with large
      aneurysms were (T/C) heterozygous for the polymorphism, while 9 of 22 patients
      (41%) with small aneurysms were (T/T or C/C) homozygous (P=0.01). The mean (+/
      SD) ruptured aneurysm diameter among all heterozygotes (8.5+/-5.2 mm) was
      significantly greater than that for C/C (6.0+/-2.3 mm) or T/T (4.7+/-1.8 mm)
      homozygotes (P=0.04). With the use of multivariate analysis, heterozygosity
      remained significantly associated with aneurysm size > or =10 mm (P=0.03).
      CONCLUSIONS: The eNOS T-786C SNP distinguishes genetically between small and
      large ruptured aneurysms. Although not predictive of SAH in the population at
      large, our data suggest that among persons with known intracranial aneurysms,
      eNOS T-786C genotype may be a factor influencing the size at which an aneurysm
      ruptures, a finding that should be taken into consideration along with other
      anatomic features of the aneurysm.

PMID- 14576374
TI  - Access to care, acculturation, and risk factors for stroke in Mexican Americans:
      the Brain Attack Surveillance in Corpus Christi (BASIC) project.
AB  - BACKGROUND AND PURPOSE: Mexican Americans are the largest subgroup of Hispanic
      Americans, now the most numerous US minority population. We compared access to
      care, acculturation, and biological risk factors among Mexican American and non
      Hispanic white stroke patients and the general population. METHODS: The Brain
      Attack Surveillance in Corpus Christi project is a population-based stroke
      surveillance study conducted in southeast Texas. All stroke cases were
      ascertained through active and passive surveillance from January 2000 through
      April 2002 and compared with population estimates from a random-digit telephone
      survey. RESULTS: Compared with non-Hispanic white stroke patients (n=405),
      Mexican American stroke patients (n=403) were less likely to have graduated from
      high school (odds ratio [OR], 15.4; 95% confidence interval [CI], 10.6 to 22.4)
      and more likely to earn less than 20 000 dollars per year (OR, 6.5; 95% CI, 4.5
      to 9.4). Mexican American stroke patients were more likely to have diabetes (OR,
      2.7; 95% CI, 2.0 to 3.7) and less likely to have atrial fibrillation (OR, 0.5;
      95% CI, 0.4 to 0.8). Compared with population estimates (n=719), stroke was
      associated with diabetes (Mexican Americans: OR, 3.6; 95% CI, 2.2 to 5.8; non
      Hispanic whites: OR, 3.0; 95% CI, 1.7 to 5.5), hypertension (Mexican Americans:
      OR, 2.8; 95% CI, 1.8 to 4.3; non-Hispanic whites: OR, 3.3; 95% CI, 2.2 to 5.0),
      lower incomes (Mexican Americans: OR, 3.4; 95% CI, 2.1 to 5.4; non-Hispanic
      whites: OR, 3.0; 95% CI, 1.7 to 5.2), and lower educational attainment (Mexican
      Americans: OR, 5.1; 95% CI, 3.2 to 8.1; non-Hispanic whites: OR, 4.5; 95% CI, 2.2
      to 9.3). CONCLUSIONS: Biological and social variables are associated with stroke
      to a similar extent in both Mexican Americans and non-Hispanic whites. Health
      behavior interventions for both populations may follow from this work. Stroke
      disparities between these populations may be explained only partially by
      differences in the prevalence of currently identified biological and social
      factors.

PMID- 14576375
TI  - Anatomy and functionality of leptomeningeal anastomoses: a review.
AB  - BACKGROUND: This review seeks to provide a structured presentation of existing
      knowledge of leptomeningeal anastomoses from anatomic and functional points of
      view and to identify problems and possible research directions to foster a better
      understanding of the subject and of stroke mechanisms. SUMMARY OF REVIEW:
      Available data show that leptomeningeal anastomoses may be important in
      understanding stroke mechanisms and that leptomeningeal anastomoses play an
      important role in penumbra outcome. However, the literature shows no consensus
      between statements on the existence of leptomeningeal anastomoses and
      compensatory capacity. CONCLUSIONS: By analyzing the available literature and
      identifying the factors that contribute to this confusion, we found that
      variability and the functional consequences thereof are important but that
      quantitative data are lacking. Moreover, vascular remodeling is an issue to
      consider.

PMID- 14576376
TI  - Stroke unit care combined with early supported discharge: long-term follow-up of
      a randomized controlled trial.
AB  - BACKGROUND AND PURPOSE: Early supported discharge from a stroke unit reduces the
      length of hospital stay. Evidence of a benefit for the patients is still unknown.
      The aim of this trial was to evaluate the long-term effects of an extended stroke
      unit service (ESUS), characterized by early supported discharge. The short-term
      effects were published previously. METHODS: We performed a randomized controlled
      trial in which 320 acute stroke patients were allocated to either ordinary stroke
      unit service (OSUS) (160 patients) or stroke unit care with early supported
      discharge (160 patients). The ESUS consists of a mobile team that coordinates
      early supported discharge and further rehabilitation. Primary outcome was the
      proportion of patients who were independent as assessed by modified Rankin Scale
      (RS) (RS < or =2=global independence). Secondary outcomes measured at 52 weeks
      were performance on the Barthel Index (BI) (BI > or =95=independent in activities
      of daily living), differences in final residence, and analyses to identify
      patients who benefited most from an early supported discharge service. All
      assessments were blinded. RESULTS: We found that 56.3% of the patients in the
      ESUS versus 45.0% in the OSUS were independent (RS < or =2) (P=0.045). The number
      needed to treat to achieve 1 independent patient in ESUS versus OSUS was 9. The
      odds ratio for independence was 1.56 (95% CI, 1.01 to 2.44). There were no
      significant differences in BI score and final residence. Patients with moderate
      to severe stroke benefited most from the ESUS. CONCLUSIONS: Stroke service based
      on treatment in a stroke unit combined with early supported discharge appears to
      improve the long-term clinical outcome compared with ordinary stroke unit care.
      Patients with moderate to severe stroke benefit most.

PMID- 14576377
TI  - Unexpected nocturnal hypoxia in patients with acute stroke.
AB  - BACKGROUND AND PURPOSE: Patients who have had a stroke are at risk of hypoxia
      through alterations in the central regulation of respiration, through aspiration,
      and through respiratory muscle weakness. Sleep-related breathing disorders are
      common and may lead to episodes of nocturnal hypoxia even when daytime
      oxygenation is normal. The aim of this study was to assess the prevalence of
      unexpected nocturnal hypoxia in stroke patients. METHODS: Consecutive adult
      patients with stroke were recruited within 72 hours of admission to hospital.
      Patients with indications for oxygen treatment were excluded. Older adults from
      the local community were recruited as control subjects. Oxygenation was assessed
      by pulse oximetry (Minolta 3i) for 5 minutes when awake before bedtime and
      continuously from 11 pm until 7 am. RESULTS: Of the 238 potentially eligible
      stroke patients, 120 were excluded because they required oxygen, 118 were
      recruited, and 100 had adequate pulse oximetry data. The mean+/-SD age was 74+/-8
      years for stroke patients and 72+/-8 years for control subjects (n=85). Mean
      awake oxygen saturation (So2) was 94.5+/-1.7% for the stroke group and 95.8+/
      1.7% for the control group (P<0.001). Mean nocturnal So2 was 93.5+/-1.9% in
      stroke patients and 94.3+/-1.9% in control subjects (P<0.01). Stroke patients had
      a higher oxygen desaturation index (ODI 4%) (8.9 versus 2.1, P<0.001). In
      addition, 23% of stroke patients spent >30 minutes with So2 <90% during the
      night. CONCLUSIONS: Oxygen saturation at night is approximately 1% lower than
      when awake. Almost a quarter of stroke patients who are normoxic at screening
      during the day spend >30 minutes with an oxygen saturation <90%.

PMID- 14576379
TI  - Editorial comment--Age-dependent brain AVM characteristics: what is the evidence?

PMID- 14576378
TI  - Effect of age on clinical and morphological characteristics in patients with
      brain arteriovenous malformation.
AB  - BACKGROUND AND PURPOSE: The goal of this work was to determine the effect of age
      at initial presentation on clinical and morphological characteristics in patients
      with brain arteriovenous malformation (AVM). METHODS: The 542 consecutive
      patients from the prospective Columbia AVM database (mean+/-SD age, 34+/-15
      years) were analyzed. Univariate statistical models were used to test the effect
      of age at initial presentation on clinical (AVM hemorrhage, seizures, headaches,
      neurological deficit, other/asymptomatic) and morphological (AVM size, venous
      drainage pattern, AVM brain location, concurrent arterial aneurysms)
      characteristics. RESULTS: Hemorrhage was the presenting symptom in 46% (n=247);
      29% (n=155) presented with seizures, 13% (n=71) with headaches, 7% (n=36) with a
      neurological deficit, and 6% (n=33) without AVM-related symptoms. Increasing age
      correlated positively with intracranial hemorrhage (P=0.001), focal neurological
      deficits (P=0.007), infratentorial AVMs (P<0.001), and concurrent arterial
      aneurysms (P<0.001); an inverse correlation was found with seizures (P<0.001),
      AVM size (P=0.001), and lobar (P<0.001), deep (P=0.008), and borderzone (P=0.014)
      location. No age differences were found for sex, headache, asymptomatic
      presentation, and venous drainage pattern. CONCLUSIONS: Our data suggest a
      significant interaction of patient age and clinical and morphological AVM
      features and argue against uniform AVM characteristics across different age
      classes at initial presentation. In particular, AVM patients diagnosed at a
      higher age show a higher fraction of AVM hemorrhage and are more likely to harbor
      additional risk factors such as concurrent arterial aneurysms and small AVM
      diameter. Longitudinal population-based AVM data are necessary to confirm these
      findings.

PMID- 14576380
TI  - Photothrombotic middle cerebral artery occlusion and reperfusion laser system in
      spontaneously hypertensive rats.
AB  - BACKGROUND AND PURPOSE: To establish a less invasive and reproducible focal
      ischemia model in the rat, we adopted a 2-laser system (ie, photothrombosis and
      YAG laser-induced reperfusion). METHODS: The distal middle cerebral artery (MCA)
      of spontaneously hypertensive rats was occluded by 568-nm krypton laser and
      intravenous infusion of the photosensitizing dye rose bengal and was recanalized
      by 355-nm ultraviolet laser irradiation. Cerebral blood flow was determined by
      laser-Doppler flowmetry at the penumbral cortex. Infarct volume was determined at
      3 days after distal MCA occlusion. RESULTS: Brain temperature determined with
      infrared thermography was maintained within an acceptable range of approximately
      1 degrees C upper shift of the center of brain temperature distribution during
      krypton or YAG laser irradiation. The average of the values (23 experiments;
      n=163) of coefficient of variation of infarct volume was 21+/-6%, indicating high
      reproducibility of this model. After distal MCA occlusion, cerebral blood flow
      was decreased to 32+/-16% of the control values and was increased to 98+/-21%
      after YAG laser-induced reperfusion. Infarct volume in these rats was 61+/-18 mm3
      (coefficient of variation=30%; n=6). CONCLUSIONS: We have characterized a highly
      reproducible focal ischemia model utilizing a 2-laser system, one to induce
      thrombotic MCA occlusion and the other to facilitate reperfusion.

PMID- 14576381
TI  - Effect of basic fibroblast growth factor treatment on brain progenitor cells
      after permanent focal ischemia in rats.
AB  - BACKGROUND AND PURPOSE: Intracisternal basic fibroblast growth factor (bFGF)
      enhances sensorimotor recovery after focal cerebral infarction in rats. One
      possible mechanism is stimulation of endogenous progenitor cells in brain. We
      investigated the effects of intracisternal bFGF on brain progenitor cells after
      stroke. METHODS: Proliferating brain cells were labeled with bromodeoxyuridine
      (BrdU) before middle cerebral artery (MCA) occlusion or sham surgery in rats.
      bFGF (0.5 microg) or vehicle was administered intracisternally at 24 and 48 hours
      after MCA occlusion, and rats were killed at 7, 14, or 21 days after stroke.
      Immunohistochemistry for BrdU and neuron- or astrocyte-specific markers was used
      to characterize progenitor cells and their progeny in the subventricular zone and
      dentate gyrus of the hippocampus. RESULTS: Infarct size did not differ among rats
      with or without bFGF treatment. MCA occlusion alone increased the number of BrdU
      labeled cells in the ipsilateral subventricular zone at days 7 to 21, and there
      was a trend toward increased cell proliferation with bFGF treatment. In the
      dentate gyrus, the number of BrdU-labeled cells was increased bilaterally after
      MCA occlusion (peak at day 7). This increase was greater after bFGF treatment. In
      the subventricular zone, 30% of BrdU-labeled cells were immunopositive for the
      immature neuron-specific marker doublecortin at day 7, and their number declined
      to 2% at day 21. In the dentate gyrus, the majority of BrdU-labeled cells
      colabeled with doublecortin at day 7, becoming NeuN positive at day 21.
      CONCLUSIONS: Stroke produces significant changes in progenitor cells in brain
      that are augmented by bFGF treatment.

PMID- 14576382
TI  - Blood pressure reduction and secondary prevention of stroke and other vascular
      events: a systematic review.
AB  - BACKGROUND: High blood pressure is a risk factor for stroke recurrence. We
      assessed the effectiveness of lowering blood pressure in preventing recurrent
      vascular events in patients with previous stroke or transient ischemic attack.
      SUMMARY OF REVIEW: We performed a systematic review and meta-regression of
      completed randomized controlled trials that investigated the effect of lowering
      blood pressure on recurrent vascular events in patients with prior ischemic or
      hemorrhagic stroke or transient ischemic attack. Trials were identified from
      searches of 3 electronic databases (Cochrane Library, EMBASE, MEDLINE). Seven
      randomized controlled trials, with 8 comparison groups, were included. Lowering
      blood pressure or treating hypertension with a variety of antihypertensive agents
      reduced stroke (odds ratio [OR], 0.76; 95% CI, 0.63 to 0.92), nonfatal stroke
      (OR, 0.79; 95% CI, 0.65 to 0.95), myocardial infarction (OR, 0.79; 95% CI, 0.63
      to 0.98), and total vascular events (OR, 0.79; 95% CI, 0.66 to 0.95). No effect
      was seen on vascular or all-cause mortality. Heterogeneity was present for
      several outcomes and was partly related to the class of antihypertensive drugs
      used; angiotensin-converting enzyme inhibitors and diuretics separately, and
      especially together, reduced vascular events, while beta-receptor antagonists had
      no discernable effect. The reduction in stroke was related to the difference in
      systolic blood pressure between treatment and control groups (P=0.002).
      CONCLUSIONS: Evidence from randomized controlled trials supports the use of
      antihypertensive agents in lowering blood pressure for the prevention of vascular
      events in patients with previous stroke or transient ischemic attack. Vascular
      prevention is associated positively with the magnitude by which blood pressure is
      reduced.

PMID- 14576383
TI  - Humanity as the model system.

PMID- 14576384
TI  - Agrobiotechnology. Mixed message could prove costly for GM crops.

PMID- 14576385
TI  - Bioweapons. Plague researcher recants account about fate of vials.

PMID- 14576386
TI  - Middle East. Islamic science is casualty of war on terrorism.

PMID- 14576387
TI  - Planetary science. Failed CONTOUR comet mission melted itself down.

PMID- 14576388
TI  - Astronomy. Asteroid returns 66 years after a close brush with Earth.

PMID- 14576389
TI  - Biomedical funding. In step with advocates, NIH backs targeted research centers.

PMID- 14576390
TI  - Paleontology. Hulking dinosaurs were buoyant but unseaworthy.

PMID- 14576391
TI  - Genetics. The Grand Canyon's cattalo.

PMID- 14576392
TI  - Scientific publishing. Opening the books on open access.

PMID- 14576393
TI  - Scientific publishing. The fight over a phrase.

PMID- 14576394
TI  - Scientific publishing. Money woes force some to change course.

PMID- 14576395
TI  - Scientific publishing. House bill triggers internecine battle.

PMID- 14576396
TI  - Modern human origins meeting. On the trail of the first dingo.

PMID- 14576397
TI  - Modern human origins meeting. Tracing the road down under.

PMID- 14576398
TI  - Molecular electronics. Next-generation technology hits an early midlife crisis.

PMID- 14576399
TI  - Biodiversity. New Chinese center marks a coming of age for field.

PMID- 14576400
TI  - A serendipitous purchase.

PMID- 14576401
TI  - Iron limitation in the Southern Ocean.

PMID- 14576402
TI  - European Union R&D spending.

PMID- 14576403
TI  - The structure of D. radiodurans.

PMID- 14576405
TI  - Comment on "14C dates from Tel Rehov: Iron-Age chronology, pharaohs, and Hebrew
      kings".

PMID- 14576406
TI  - Education. The long road to race-blindness.

PMID- 14576407
TI  - Cancer. A risky business--assessing breast cancer risk.

PMID- 14576408
TI  - Plant sciences. How legumes select their sweet talking symbionts.

PMID- 14576409
TI  - Geophysics. Glacial flow goes seismic.

PMID- 14576410
TI  - Cell signaling. The BRCT domain: signaling with friends?

PMID- 14576411
TI  - Geochemistry. The importance of being alkaline.

PMID- 14576412
TI  - Atmospheric science. An environmental experiment with H2?

PMID- 14576413
TI  - Amersham Prize winner. Expanding the genetic code.

PMID- 14576414
TI  - Amersham Prize. 2002 grand prize winner.

PMID- 14576416
TI  - Preventing toxicity with a gene test.

PMID- 14576417
TI  - First check my genome, doctor.

PMID- 14576418
TI  - The twists and turns in BRCA's path.

PMID- 14576420
TI  - Race and medicine.

PMID- 14576419
TI  - Choices--and uncertainties--for women with BRCA mutations.

PMID- 14576421
TI  - Genomics and global health: time for a reappraisal.
AB  - Although currently there are only a limited number of genomic technologies that
      are applicable to health care in the developing countries, this is unlikely to be
      the case in the near future. If, however, the full potential of genomics for
      health care is to be fulfilled, there will have to be a complete change of
      emphasis in education and research in the richer countries toward a more global
      view of disease and its consequences.

PMID- 14576422
TI  - Genomic priorities and public health.
AB  - Given the continuing difficulty of identifying genes for complex disorders in a
      robust, replicable manner, and the extensive resources devoted to this effort, it
      is becoming increasingly important to analyze the relative benefits of genomics
      research for public health applications and for the understanding of disease
      pathogenesis. To establish priorities for genetics research, we review and
      evaluate several characteristics of selected exemplary complex diseases,
      including phenotypic accuracy, knowledge of specific and nonspecific genetic and
      environmental risk factors, and population prevalence and impact. We propose that
      complex diseases with the strongest evidence for genetic etiology, limited
      ability to modify exposure or risk factors, and high public health impact should
      have the highest priority for genetics research.

PMID- 14576423
TI  - Reverse vaccinology and genomics.
AB  - The genomic revolution has had a dramatic effect on our ability to find new
      vaccine targets and develop effective vaccines.

PMID- 14576424
TI  - Attrition and translation.
AB  - The recently published NIH Roadmap proposes that public-sector science should
      place increased emphasis on the development of new therapeutics and diagnostics
      based on the fruits of fundamental research. Such "translational research"
      activities, traditionally the province of the private sector, have long been
      compromised by high rates of attrition (failure during the course of preclinical
      or clinical development of therapeutics). Attrition has led to growing financial
      costs, as well as opportunity costs. The new focus offers a way to reverse these
      trends, especially if the scientific community can improve on its ability to
      reconcile molecular genetic research with integrative organ- and organism-based
      research.

PMID- 14576425
TI  - Molecular imaging: looking at problems, seeing solutions.
AB  - Noninvasive molecular-imaging technologies are providing researchers with
      exciting new opportunities to study small-animal models of human disease. With
      continued improvements in instrumentation, identification of better imaging
      targets by genome-based approaches, and design of better imaging probes by
      innovative chemistry, these technologies promise to play increasingly important
      roles in disease diagnosis and therapy.

PMID- 14576426
TI  - Healthy animals with extreme longevity.

PMID- 14576427
TI  - Generating diverse skeletons of small molecules combinatorially.
AB  - Lack of efficient access to collections of synthetic compounds that have skeletal
      diversity is a key bottleneck in the small-molecule discovery process. We report
      a synthesis strategy that involves transforming substrates with different
      appendages that pre-encode skeletal information, named sigma elements, into
      products that have different skeletons with the use of common reaction
      conditions. With this approach, split-pool synthesis can be used to pre-encode
      skeletal diversity combinatorially and thereby generate such small molecules very
      efficiently. A split-pool synthesis of more than 1000 compounds produced
      overlapping, combinatorial matrices of molecular skeletons and appended building
      blocks in both enantiomeric and diastereomeric forms.

PMID- 14576429
TI  - Air pollution and climate-forcing impacts of a global hydrogen economy.
AB  - If today's surface traffic fleet were powered entirely by hydrogen fuel cell
      technology, anthropogenic emissions of the ozone precursors nitrogen oxide (NOx)
      and carbon monoxide could be reduced by up to 50%, leading to significant
      improvements in air quality throughout the Northern Hemisphere. Model simulations
      of such a scenario predict a decrease in global OH and an increased lifetime of
      methane, caused primarily by the reduction of the NOx emissions. The sign of the
      change in climate forcing caused by carbon dioxide and methane depends on the
      technology used to generate the molecular hydrogen. A possible rise in
      atmospheric hydrogen concentrations is unlikely to cause significant
      perturbations of the climate system.

PMID- 14576428
TI  - Experimental models of primitive cellular compartments: encapsulation, growth,
      and division.
AB  - The clay montmorillonite is known to catalyze the polymerization of RNA from
      activated ribonucleotides. Here we report that montmorillonite accelerates the
      spontaneous conversion of fatty acid micelles into vesicles. Clay particles often
      become encapsulated in these vesicles, thus providing a pathway for the prebiotic
      encapsulation of catalytically active surfaces within membrane vesicles. In
      addition, RNA adsorbed to clay can be encapsulated within vesicles. Once formed,
      such vesicles can grow by incorporating fatty acid supplied as micelles and can
      divide without dilution of their contents by extrusion through small pores. These
      processes mediate vesicle replication through cycles of growth and division. The
      formation, growth, and division of the earliest cells may have occurred in
      response to similar interactions with mineral particles and inputs of material
      and energy.

PMID- 14576430
TI  - Discovery of olivine in the Nili Fssae region of Mars.
AB  - We have detected a 30,000-square-kilometer area rich in olivine in the Nili
      Fossae region of Mars. Nili Fossae has been interpreted as a complex of grabens
      and fractures related to the formation of the Isidis impact basin. We propose
      that post-impact faulting of this area has exposed subsurface layers rich in
      olivine. Linear mixture analysis of Thermal Emission Spectrometer spectra shows
      surface exposures of 30% olivine, where the composition of the olivine ranges
      from Fo30 to Fo70.

PMID- 14576431
TI  - Kin discrimination and the benefit of helping in cooperatively breeding
      vertebrates.
AB  - In many cooperatively breeding vertebrates, a dominant breeding pair is assisted
      in offspring care by nonbreeding helpers. A leading explanation for this
      altruistic behavior is Hamilton's idea that helpers gain indirect fitness
      benefits by rearing relatives (kin selection). Many studies have shown that
      helpers typically provide care for relatives, but relatively few have shown that
      helpers provide closer kin with preferential care (kin discrimination), fueling
      the suggestion that kin selection only poorly accounts for the evolution of
      cooperative breeding in vertebrates. We used meta-analysis to show that (i)
      individuals consistently discriminate between kin, and (ii) stronger
      discrimination occurs in species where the benefits of helping are greater. These
      results suggest a general role for kin selection and that the relative importance
      of kin selection varies across species, as predicted by Hamilton's rule.

PMID- 14576432
TI  - BRCT repeats as phosphopeptide-binding modules involved in protein targeting.
AB  - We used a proteomic approach to identify phosphopeptide-binding modules mediating
      signal transduction events in the DNA damage response pathway. Using a library of
      partially degenerate phosphopeptides, we identified tandem BRCT (BRCA1 carboxyl
      terminal) domains in PTIP (Pax transactivation domain-interacting protein) and in
      BRCA1 as phosphoserine- or phosphothreonine-specific binding modules that
      recognize substrates phosphorylated by the kinases ATM (ataxia telangiectasia
      mutated) and ATR (ataxia telangiectasia- and RAD3-related) in response to gamma
      irradiation. PTIP tandem BRCT domains are responsible for phosphorylation
      dependent protein localization into 53BP1- and phospho-H2AX (gamma-H2AX)
      containing nuclear foci, a marker of DNA damage. These findings provide a
      molecular basis for BRCT domain function in the DNA damage response and may help
      to explain why the BRCA1 BRCT domain mutation Met1775 --> Arg, which fails to
      bind phosphopeptides, predisposes women to breast and ovarian cancer.

PMID- 14576433
TI  - The BRCT domain is a phospho-protein binding domain.
AB  - The carboxyl-terminal domain (BRCT) of the Breast Cancer Gene 1 (BRCA1) protein
      is an evolutionarily conserved module that exists in a large number of proteins
      from prokaryotes to eukaryotes. Although most BRCT domain-containing proteins
      participate in DNA-damage checkpoint or DNA-repair pathways, or both, the
      function of the BRCT domain is not fully understood. We show that the BRCA1 BRCT
      domain directly interacts with phosphorylated BRCA1-Associated Carboxyl-terminal
      Helicase (BACH1). This specific interaction between BRCA1 and phosphorylated
      BACH1 is cell cycle regulated and is required for DNA damage-induced checkpoint
      control during the transition from G2 to M phase of the cell cycle. Further, we
      show that two other BRCT domains interact with their respective physiological
      partners in a phosphorylation-dependent manner. Thirteen additional BRCT domains
      also preferentially bind phospho-peptides rather than nonphosphorylated control
      peptides. These data imply that the BRCT domain is a phospho-protein binding
      domain involved in cell cycle control.

PMID- 14576434
TI  - Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2.
AB  - Risks of breast and ovarian cancer were determined for Ashkenazi Jewish women
      with inherited mutations in the tumor suppressor genes BRCA1 and BRCA2. We
      selected 1008 index cases, regardless of family history of cancer, and carried
      out molecular analysis across entire families. The lifetime risk of breast cancer
      among female mutation carriers was 82%, similar to risks in families with many
      cases. Risks appear to be increasing with time: Breast cancer risk by age 50
      among mutation carriers born before 1940 was 24%, but among those born after 1940
      it was 67%. Lifetime risks of ovarian cancer were 54% for BRCA1 and 23% for BRCA2
      mutation carriers. Physical exercise and lack of obesity in adolescence were
      associated with significantly delayed breast cancer onset.

PMID- 14576435
TI  - Structure of Rab GDP-dissociation inhibitor in complex with prenylated YPT1
      GTPase.
AB  - Rab/Ypt guanosine triphosphatases (GTPases) represent a family of key membrane
      traffic regulators in eukaryotic cells whose function is governed by the
      guanosine diphosphate (GDP) dissociation inhibitor (RabGDI). Using a combination
      of chemical synthesis and protein engineering, we generated and crystallized the
      monoprenylated Ypt1:RabGDI complex. The structure of the complex was solved to
      1.5 angstrom resolution and provides a structural basis for the ability of RabGDI
      to inhibit the release of nucleotide by Rab proteins. Isoprenoid binding requires
      a conformational change that opens a cavity in the hydrophobic core of its domain
      II. Analysis of the structure provides a molecular basis for understanding a
      RabGDI mutant that causes mental retardation in humans.

PMID- 14576436
TI  - A new class of bacterial RNA polymerase inhibitor affects nucleotide addition.
AB  - RNA polymerase (RNAP) is the central enzyme of gene expression. Despite
      availability of crystal structures, details of its nucleotide addition cycle
      remain obscure. We describe bacterial RNAP inhibitors (the CBR703 series) whose
      properties illuminate this mechanism. These compounds inhibit known catalytic
      activities of RNAP (nucleotide addition, pyrophosphorolysis, and Gre-stimulated
      transcript cleavage) but not translocation of RNA or DNA when translocation is
      uncoupled from catalysis. CBR703-resistance substitutions occur on an outside
      surface of RNAP opposite its internal active site. We propose that CBR703
      compounds inhibit nucleotide addition allosterically by hindering movements of
      active site structures that are linked to the CBR703 binding site through a
      bridge helix.

PMID- 14576437
TI  - Immune control of tuberculosis by IFN-gamma-inducible LRG-47.
AB  - Interferon-gamma (IFN-gamma) provides an essential component of immunity to
      tuberculosis by activating infected host macrophages to directly inhibit the
      replication of Mycobacterium tuberculosis (Mtb). IFN-gamma-inducible nitric oxide
      synthase 2 (NOS2) is considered a principal effector mechanism, although other
      pathways may also exist. Here, we identify one member of a newly emerging 47
      kilodalton (p47) guanosine triphosphatase family, LRG-47, that acts independently
      of NOS2 to protect against disease. Mice lacking LRG-47 failed to control Mtb
      replication, unlike those missing the related p47 guanosine triphosphatases IRG
      47 or IGTP. Defective bacterial killing in IFN-gamma-activated LRG-47-/-
      macrophages was associated with impaired maturation of Mtb-containing phagosomes,
      vesicles that otherwise recruited LRG-47 in wild-type cells. Thus, LRG-47 may
      serve as a critical vacuolar trafficking component used to dispose of
      intracellular pathogens like Mtb.

PMID- 14576438
TI  - HCV persistence and immune evasion in the absence of memory T cell help.
AB  - Spontaneous resolution of hepatitis C virus (HCV) infection in humans usually
      affords long-term immunity to persistent viremia and associated liver diseases.
      Here, we report that memory CD4+ Tcells are essential for this protection.
      Antibody-mediated depletion of CD4+ Tcells before reinfection of two immune
      chimpanzees resulted in persistent, low-level viremia despite functional intra
      hepatic memory CD8+ Tcell responses. Incomplete control of HCV replication by
      memory CD8+ Tcells in the absence of adequate CD4+ Tcell help was associated with
      emergence of viral escape mutations in class I major histocompatibility complex
      restricted epitopes and failure to resolve HCV infection.

PMID- 14576439
TI  - A cellular framework for gut-looping morphogenesis in zebrafish.
AB  - Many vertebrate organs adopt asymmetric positions with respect to the midline,
      but little is known about the cellular changes and tissue movements that occur
      downstream of left-right gene expression to produce this asymmetry. Here, we
      provide evidence that the looping of the zebrafish gut results from the
      asymmetric migration of the neighboring lateral plate mesoderm (LPM). Mutations
      that disrupt the epithelial structure of the LPM perturb this asymmetric
      migration and inhibit gut looping. Asymmetric LPM migration still occurs when the
      endoderm is ablated from the gut-looping region, suggesting that the LPM can
      autonomously provide a motive force for gut displacement. Finally, reducing left
      sided Nodal activity randomizes the pattern of LPM migration and gut looping.
      These results reveal a cellular framework for the regulation of organ laterality
      by asymmetrically expressed genes.

PMID- 14576440
TI  - Targeted protein degradation and synapse remodeling by an inducible protein
      kinase.
AB  - Synaptic plasticity involves the reorganization of synapses at the protein and
      the morphological levels. Here, we report activity-dependent remodeling of
      synapses by serum-inducible kinase (SNK). SNK was induced in hippocampal neurons
      by synaptic activity and was targeted to dendritic spines. SNK bound to and
      phosphorylated spine-associated Rap guanosine triphosphatase activating protein
      (SPAR), a postsynaptic actin regulatory protein, leading to degradation of SPAR.
      Induction of SNK in hippocampal neurons eliminated SPAR protein, depleted
      postsynaptic density-95 and Bassoon clusters, and caused loss of mature dendritic
      spines. These results implicate SNK as a mediator of activity-dependent change in
      the molecular composition and morphology of synapses.

PMID- 14576441
TI  - A transient rise in tropical sea surface temperature during the Paleocene-Eocene
      thermal maximum.
AB  - The Paleocene-Eocene Thermal Maximum (PETM) has been attributed to a rapid rise
      in greenhouse gas levels. If so, warming should have occurred at all latitudes,
      although amplified toward the poles. Existing records reveal an increase in high
      latitude sea surface temperatures (SSTs) (8 degrees to 10 degrees C) and in
      bottom water temperatures (4 degrees to 5 degrees C). To date, however, the
      character of the tropical SST response during this event remains unconstrained.
      Here we address this deficiency by using paired oxygen isotope and minor element
      (magnesium/calcium) ratios of planktonic foraminifera from a tropical Pacific
      core to estimate changes in SST. Using mixed-layer foraminifera, we found that
      the combined proxies imply a 4 degrees to 5 degrees C rise in Pacific SST during
      the PETM. These results would necessitate a rise in atmospheric pCO2 to levels
      three to four times as high as those estimated for the late Paleocene.

PMID- 14576442
TI  - Regulation of NF-kappaB-dependent lymphocyte activation and development by
      paracaspase.
AB  - Paracaspase (MALT1), a member of an evolutionarily conserved superfamily of
      caspase-like proteins, has been shown to bind and colocalize with the protein
      Bcl10 in vitro and, because of this association, has been suggested to be
      involved in the CARMA1-Bcl10 pathway of antigen-induced nuclear factor kappaB (NF
      kappaB) activation. We demonstrate that primary T and B lymphocytes from
      paracaspase-deficient mice are defective in antigen-receptor-induced NF-kappaB
      activation, cytokine production, and proliferation. Paracaspase acts downstream
      of Bcl10 to induce NF-kappaB activation and is required for the normal
      development of B cells, indicating that paracaspase provides the missing link
      between Bcl10 and activation of the IkappaB kinase complex.

PMID- 14576443
TI  - Asbestosis and idiopathic pulmonary fibrosis: comparison of thin-section CT
      features.
AB  - PURPOSE: To identify differences, if any, in thin-section computed tomographic
      (CT) features between asbestosis and idiopathic pulmonary fibrosis (IPF) and to
      test the findings in a subset of histopathologically proved cases of usual
      interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP).
      MATERIALS AND METHODS: Consecutive patients with a diagnosis of IPF (n = 212) or
      asbestosis (n = 74) were included. The relationships derived from the initial
      comparison were tested in a separate group of biopsy-proved UIP (n = 30) and NSIP
      (n = 23) cases. Two observers independently scored thin-section CT images for
      extent, distribution, and coarseness of fibrosis; proportion of ground-glass
      opacification; severity of traction bronchiectasis; and extent of emphysema.
      RESULTS: After controlling for extent of fibrosis, patients with asbestosis had
      coarser fibrosis than those with IPF (odds ratio, 1.52; 95% CI: 1.25, 1.84; P
      <.001). Compared with the biopsy-proved cases, the asbestosis cases involved
      coarser fibrosis (after controlling for disease extent) than the NSIP cases (odds
      ratio, 2.48; 95% CI: 1.49, 4.11; P <.001) but fibrosis similar to that in the UIP
      cases. A basal and subpleural distribution of disease was usual in all subgroups
      but significantly more prevalent (P, <.01 to.001) with asbestosis than with UIP
      or NSIP. CONCLUSION: The thin-section CT pattern of asbestosis closely resembles
      that of biopsy-proved UIP and differs markedly from that of biopsy-proved NSIP.

PMID- 14576444
TI  - Hepatic vein stenosis after living donor liver transplantation: evaluation with
      Doppler US.
AB  - PURPOSE: To determine the spectral Doppler ultrasonographic (US) findings that
      would indicate hepatic vein stenosis after living donor liver transplantation
      (LDLT). MATERIALS AND METHODS: The authors retrospectively reviewed postoperative
      Doppler US images of the hepatic veins in 113 consecutive patients who underwent
      LDLT. Doppler US was performed 1-25 times (mean, 5.2 times) during 1-433 days
      after LDLT. Nineteen patients who were inadequate for analysis were excluded;
      thus, 94 patients (72 male patients and 22 female patients; mean age, 40 years)
      were included in the study. Patients with more than 10 mm Hg of pressure gradient
      between the hepatic vein and the inferior vena cava were considered to have
      substantial hepatic vein stenosis (stenosis group). Those without substantial
      stenosis (control group) included patients with no clinical or radiologic
      evidence of hepatic vein stenosis for at least 3 months after LDLT. The wave
      pattern and peak flow velocity of the hepatic veins were compared between the
      groups. RESULTS: Five patients (5%) had substantial hepatic vein stenosis: three
      had persistent monophasic wave patterns at all US examinations, and two had
      monophasic wave patterns at most US examinations and biphasic or triphasic wave
      patterns at 6- and 9-day follow-up examinations. In the control group, 52 (58%)
      of 89 patients had a persistent triphasic or biphasic wave pattern and 37 (42%)
      had a monophasic wave pattern at one or more US examinations; this included two
      patients with persistent monophasic wave patterns. A monophasic wave pattern was
      more frequent in the stenosis group than in the control group (P =.015). There
      was no significant difference between the velocities of the hepatic veins in the
      stenosis group (22.3 cm/sec +/- 9.6 [SD]) and those in the control group (37.5
      cm/sec +/- 20.3) (P =.14). CONCLUSION: A persistent monophasic wave pattern on
      Doppler US images of the hepatic veins is suggestive of, but not specific for,
      substantial hepatic vein stenosis after LDLT. A persistent triphasic wave pattern
      on Doppler US images can exclude the possibility of substantial stenosis.

PMID- 14576445
TI  - MR imaging in the diagnosis of denervated and reinnervated skeletal muscles:
      experimental study in rats.
AB  - PURPOSE: To describe the magnetic resonance (MR) imaging findings of denervation
      and reinnervation of skeletal muscles in rats. MATERIALS AND METHODS: The
      posterior tibial nerve was transected in 48 rats (nerve section group) and was
      repaired just after transection in another 48 rats (nerve repair group). At 2, 4,
      6, and 8 weeks after surgery, changes in the area and signal intensity of the
      gastrocnemius muscle on T1- and T2-weighted MR images in vivo (four rats in each
      group) and T1s and T2s were analyzed in vitro in both groups (20 rats each) and
      compared with electromyographic findings. Water volume content and extracellular
      fluid space of the muscle in vitro were also examined in both groups (24 rats
      each). Four rats were used as controls for in vitro analysis. RESULTS: At T2
      weighted MR imaging, the muscle showed continuously high signal intensity in the
      nerve section group. In the nerve repair group, the signal intensity was high
      until 4 weeks, when it recovered. Increases in signal intensity on T2-weighted MR
      images and T2s were seen in the nerve section group throughout the study period.
      In the nerve repair group, increased signal intensity on T2-weighted MR images
      was noted at 2 and 4 weeks and significantly returned to normal at 6 weeks (P
      <.014), just after the detection of the M wave at electromyography. T2 increased
      at 2 weeks, then decreased significantly at 4 weeks (P =.012). Extracellular
      fluid space significantly increased in the nerve section group at all measurement
      times and in the nerve repair group at 2 and 4 weeks, then it decreased after 6
      weeks (P <.003), which is parallel to the change in signal intensity on T2
      weighted MR images, although there was little change in total water volume
      content in either group. CONCLUSION: Changes in signal intensity on T2-weighted
      MR images that are related to denervation may result from an increase of
      extracellular fluid space. MR imaging clearly demonstrates that changes in rat
      skeletal muscle are reversed when the nerve heals and reinnervation proceeds.

PMID- 14576446
TI  - Quantification of breast tumor microvascular permeability with feruglose-enhanced
      MR imaging: initial phase II multicenter trial.
AB  - PURPOSE: To investigate use of the macromolecular contrast agent feruglose for
      differentiating and grading of human benign and malignant breast tumors on the
      basis of their microvascular characteristics. MATERIALS AND METHODS: Sixty-three
      women with 63 primary breast lesions were examined with dynamic T1-weighted
      gradient-echo magnetic resonance (MR) imaging after intravenous injection of
      feruglose. A two-compartment unidirectional kinetic model applied to the dynamic
      data yielded estimates of the endothelial transfer coefficient, KPS, and the
      fractional plasma volume of the tumors. These MR imaging-derived parameters were
      correlated with the histologic tumor grade and quantified according to the Scarff
      Bloom-Richardson (SBR) score by means of Pearson product moment correlation
      analyses. Differences between malignant and nonmalignant breast lesions with
      respect to KPS for feruglose were evaluated by means of the chi2 test and by
      calculating the sensitivity, specificity, and positive and negative predictive
      values. RESULTS: Histologic analysis revealed 26 benign and 37 malignant tumors.
      A moderate yet statistically significant correlation between KPS and SBR score
      was found (R = 0.496, P <.001). No significant correlation was observed between
      fractional plasma volume and SBR score (R = 0.085, P =.507). The KPS values were
      zero for 19 (73%) of the 26 benign tumors and were greater than zero for 27 (73%)
      of the 37 carcinomas. This distribution was significantly different (chi2 =
      13.035, P =.001). With the criterion KPS > 0 in carcinomas, sensitivity was 0.73,
      specificity was 0.73, and the positive predictive value was 0.79. CONCLUSION:
      Quantitative measures of tumor microvascular permeability can be used for breast
      tumor characterization. The probability of breast tumor microvascular
      hyperpermeability to be associated with malignancy is 79%.

PMID- 14576447
TI  - Population-based mammography screening: comparison of screen-film and full-field
      digital mammography with soft-copy reading--Oslo I study.
AB  - PURPOSE: To compare screen-film and full-field digital mammography with soft-copy
      reading in a population-based screening program. MATERIALS AND METHODS: Full
      field digital and screen-film mammography were performed in 3,683 women aged 50
      69 years. Two standard views of each breast were acquired with each modality.
      Images underwent independent double reading with use of a five-point rating scale
      for probability of cancer. Recall rates and positive predictive values were
      calculated. Cancer detection rates determined with both modalities were compared
      by using the McNemar test for paired proportions. Retrospective side-by-side
      analysis for conspicuity of cancers was performed by an external independent
      radiologist group with experience in both modalities. RESULTS: In 3,683 cases, 31
      cancers were detected. Screen-film mammography depicted 28 (0.76%) malignancies,
      and full-field digital mammography depicted 23 (0.62%) malignancies. The
      difference between cancer detection rates was not significant (P =.23). The
      recall rate for full-field digital mammography (4.6%; 168 of 3,683 cases) was
      slightly higher than that for screen-film mammography (3.5%; 128 of 3,683 cases).
      The positive predictive value based on needle biopsy results was 46% for screen
      film mammography and 39% for full-field digital mammography. Side-by-side image
      comparison for cancer conspicuity led to classification of 19 cancers as equal
      for probability of malignancy, six cancers as slightly better demonstrated at
      screen-film mammography, and six cancers as slightly better demonstrated at full
      field digital mammography. CONCLUSION: There was no statistically significant
      difference in cancer detection rate between screen-film and full-field digital
      mammography. Cancer conspicuity was equal with both modalities. Full-field
      digital mammography with soft-copy reading is comparable to screen-film
      mammography in population-based screening.

PMID- 14576448
TI  - White matter and cerebral metabolite changes in children undergoing treatment for
      acute lymphoblastic leukemia: longitudinal study with MR imaging and 1H MR
      spectroscopy.
AB  - PURPOSE: To assess the development of white matter and cerebral metabolite
      changes during and after treatment in children with acute lymphoblastic leukemia.
      MATERIALS AND METHODS: Twenty-three children (10 boys, mean age of 6.3 years; 13
      girls, mean age of 6.6 years) with acute lymphoblastic leukemia were examined
      prospectively with magnetic resonance (MR) imaging and MR spectroscopy at 0, 8,
      and 20 weeks and 1, 2, and 3 years after diagnosis. White matter changes were
      diagnosed on the basis of hyperintense abnormalities on T2-weighted MR images.
      Single-voxel hydrogen 1 MR spectroscopy results from the right frontoparietal
      region of 21 children who received intravenous high-dose methotrexate were
      analyzed for cerebral metabolite changes. Multilevel models were used to assess
      the change in metabolites from baseline levels at subsequent follow-up. RESULTS:
      At 20 weeks, MR spectroscopy showed a significant reduction (P <.05) of mean N
      acetylaspartate to choline ratio and increase in mean choline to creatine ratio
      (P <.05) in the children given high-dose methotrexate. This decline in N
      acetylaspartate to choline ratio subsequently reversed and increased, possibly
      because of normal age-related brain maturation. Seventeen of 21 (81%) children
      showed metabolite changes at MR spectroscopy, while five of 22 (23%) showed white
      matter changes at MR imaging at 20 weeks. One more child developed white matter
      changes at 32 weeks. The associated changes resolved or reduced with time.
      CONCLUSION: MR spectroscopy demonstrated metabolite changes in the brain after
      high-dose methotrexate treatment in the absence of structural white matter
      abnormalities at MR imaging. MR spectroscopy might thus be a more sensitive
      method of monitoring the effects of high-dose methotrexate in the brain.

PMID- 14576450
TI  - DNA repair in photoreceptor survival.
AB  - Light triggers a sequence of events that damage photoreceptor cells within the
      superior central portion of the retina, resulting in apoptotic cell death. This
      damage is mediated by energy absorbed by rhodopsin and the intermediates of the
      rhodopsin-bleaching process. Furthermore, inhibition of the visual cycle and the
      re-isomerization of all-trans retinol preserve photoreceptors. We have recently
      shown light-induced DNA fragmentation to occur only within photoreceptors, and,
      in time-courses following light treatment, these cells exhibit two peaks of
      damage, approx 24 h apart. This was also observed by quantification of nucleosome
      length DNA fragments and their multimers (DNA ladders) as well as by highly
      repetitive short interspersed nuclear element (SINE) analysis. This bimodal
      pattern of photoreceptor DNA fragmentation suggests two populations of cells, and
      each of these were affected by light at a different rate or time. However, the
      rat retina is composed of 500 nm-sensitive rods, and approx 2% cones, suggesting
      that a two-cell-type hypothesis is incorrect. Thus, there is a possibility that
      light-induced DNA fragmentation is triggered and that some photoreceptors are
      able to initiate a repair mechanism, resulting in a temporary decrease in DNA
      damage followed by another wave of fragmentation that ultimately leads to cell
      death. Subsequently, we observed that the repair enzyme DNA polymerase beta was
      upregulated following light treatment, again suggesting the presence of a repair
      mechanism. Our results suggest that a DNA-repair mechanism exists within
      photoreceptors, and indicate that manipulation of this process may provide
      additional protection and/or recovery from events that trigger DNA fragmentation
      and apoptotic cell death in photoreceptors.

PMID- 14576452
TI  - Retinal remodeling in inherited photoreceptor degenerations.
AB  - Photoreceptor degenerations initiated in rods or the retinal pigmented epithelium
      usually evoke secondary cone death and sensory deafferentation of the surviving
      neural retina. In the mature central nervous system, deafferentation evokes
      atrophy and connective re-patterning. It has been assumed that the neural retina
      does not remodel, and that it is a passive survivor. Screening of advanced stages
      of human and rodent retinal degenerations with computational molecular
      phenotyping has exposed a prolonged period of aggressive negative remodeling in
      which neurons migrate along aberrant glial columns and seals, restructuring the
      adult neural retina (1). Many neurons die, but survivors rewire the remnant inner
      plexiform layer (IPL), forming thousands of novel ectopic microneuromas in the
      remnant inner nuclear layer (INL). Bipolar and amacrine cells engage in new
      circuits that are most likely corruptive. Remodeling in human and rodent retinas
      emerges regardless of the molecular defects that initially trigger retinal
      degenerations. Although remodeling may constrain therapeutic intervals for
      molecular, cellular, or bionic rescue, the exposure of intrinsic retinal
      remodeling by the removal of sensory control in retinal degenerations suggests
      that neuronal organization in the normal retina may be more plastic than
      previously believed.

PMID- 14576451
TI  - Light regulation of the insulin receptor in the retina.
AB  - The peptide hormone insulin binds its cognate cell-surface receptors to activate
      a coordinated biochemical-signaling network and to induce intracellular events.
      The retina is an integral part of the central nervous system and is known to
      contain insulin receptors, although their function is unknown. This article,
      describes recent studies that link the photobleaching of rhodopsin to tyrosine
      phosphorylation of the insulin receptor and subsequent activation of
      phosphoinositide 3- kinase (PI3K). We recently found a light-dependent increase
      in tyrosine phosphorylation of the insulin receptor-beta-subunit (IR beta) and an
      increase in PI3K enzyme activity in isolated rod outer segments (ROS) and in anti
      phosphotyrosine (PY) and anti-IR beta immunoprecipitates of retinal homogenates.
      The light effect, which was localized to photoreceptor neurons, is independent of
      insulin secretion. Our results suggest that light induces tyrosine
      phosphorylation of IR beta in outer-segment membranes, which leads to the binding
      of p85 through its N-terminal SH2 domain and the generation of PI-3,4,5-P3. We
      suggest that the physiological role of this process may be to provide
      neuroprotection of the retina against light damage by activating proteins that
      protect against stress-induced apoptosis. The studies linking PI3K activation
      through tyrosine phosphorylation of IR beta now provide physiological relevance
      for the presence of these receptors in the retina.

PMID- 14576453
TI  - The nature of dominant mutations of rhodopsin and implications for gene therapy.
AB  - Mutations in the rhodopsin gene are the most common cause of retinitis pigmentosa
      (RP) among human patients. The nature of the rhodopsin mutations has critical
      implications for the design of strategies for gene therapy. Nearly all rhodopsin
      mutations are dominant. Although dominance does not arise because of
      haploinsufficiency, it is unclear whether it is caused by gain-of-function or
      dominant-negative mutations. Current strategies for gene therapy have been
      devised to deal with toxic, gain-of-function mutations. However, analysis of
      results of transgenic and targeted expression of various rhodopsin genes in mice
      suggests that dominance may arise as a result of dominant-negative mutations.
      This has important consequences for gene therapy. The effects of dominant
      negative mutations can be alleviated, in principle, by supplementation with
      additional wild-type rhodopsin. If added wild-type rhodopsin could slow retinal
      degeneration in human patients, as it does in mice, it would represent a valuable
      new strategy for gene therapy of RP caused by dominant rhodopsin mutations.

PMID- 14576454
TI  - Experimental retinal reattachment: a new perspective.
AB  - In the feline model, retinal detachment initiates a cascade of changes that
      include photoreceptor- cell "deconstruction," apoptotic death of some
      photoreceptors, neurite outgrowth from second- and third-order neurons,
      remodeling of photoreceptor synaptic terminals, and Muller-cell gliosis. We have
      previously shown that reattachment within 24 h halts or reverses many of these
      presumed detrimental changes. However, in patients with retinal detachments,
      reattachment cannot always be performed within this 24-h window. Moreover,
      recovery of vision following successful reattachment surgery in the macula is
      often imperfect. Here, we examine the ability of relatively long-term
      reattachment (28 d) to stop or reverse several cellular events that occur at 3 d
      of detachment. In contrast to earlier studies of reattachment, which focused on
      the regeneration of outer segments, we focus our attention here on other cellular
      events such as neuronal remodeling and gliosis. Some of these changes are
      reversed by reattachment, but reattachment itself appears to stimulate other
      changes that are not associated with detachment. The implications of these events
      for the return of vision are unknown, but they do indicate that simply
      reattaching the retina does not return the retina to its pre-detachment state
      within 28 d.

PMID- 14576458
TI  - An oath for bioscientists.
AB  - In this paper, by examining the idea of a 'Hippocratic Oath for scientists',
      promoted by Sir Joseph Rotblat, oaths for medical professionals and scientists
      and the definitions and relationships of different moral norms such as oaths,
      codes and guidelines, we propose an oath for bioscientists with justifications
      based on professional and organizational ethics.

PMID- 14576459
TI  - Receptors of glutamate and neurotrophin in vestibular neuronal functions.
AB  - The last decade has witnessed advances in understanding the roles of receptors of
      neurotrophin and glutamate in the vestibular system. In the first section of this
      review, the biological actions of neurotrophins and their receptors in the
      peripheral and central vestibular systems are summarized. Emphasis will be placed
      on the roles of neurotrophins in developmental plasticity and in the maintenance
      of vestibular function in the adult animal. This is reviewed in relation to the
      developmental expression pattern of neurotrophins and their receptors within the
      vestibular nuclei. The second part is focused on the functional role of different
      glutamate receptors on central vestibular neurons. The developmental expression
      pattern of glutamate receptor subunits within the vestibular nuclei is reviewed
      in relation to the potential role of glutamate receptors in regulating the
      development of vestibular function.

PMID- 14576455
TI  - Age-related macular degeneration and retinal pigment epithelium wound healing.
AB  - Choroidal new vessel (CNV) excision may improve vision in patients with age
      related macular degeneration (AMD) by eliminating the source of subretinal
      bleeding and scarring. Visual recovery after CNV excision is usually poor in AMD
      patients, probably because of removal of the associated retinal pigment
      epithelium (RPE), coupled with the inability of native RPE at the edge of the
      dissection bed to resurface the iatrogenic RPE defect. Experiments using in vitro
      and in vivo RPE wound-healing models have provided insight into the factors that
      regulate RPE wound healing in situ.Wound-healing studies using aged submacular
      human Bruch's membrane in organ culture show that resurfacing of localized RPE
      defects is influenced by the depth of damage to Bruch's membrane as well as
      factors that are intrinsic to the aged RPE at the wound edge. The Bruch's
      membrane organ-culture paradigm provides a surface for RPE wound healing that
      closely resembles the surface on which RPE must grow after CNV excision in AMD
      patients. An understanding of the factors that influence RPE wound healing might
      lead to treatments that stimulate RPE resurfacing and improve visual outcome
      after CNV excision.

PMID- 14576456
TI  - Molecular substrates of potassium spatial buffering in glial cells.
AB  - It is generally accepted that the foremost mechanism for the buffering of K+ from
      the extracellular space ([K+]o) in the brain is "K+ spatial buffering." This is
      the process by which glial cells dissipate local K+ gradients by transferring K+
      ions from areas of high to low [K+]o. These glial K+ fluxes are mediated mainly
      by inwardly rectifying K+ (Kir) channels. The K+ spatial buffering hypothesis has
      been tested and confirmed in the retina, in which is has been termed as "K+
      siphoning". In Muller cells, the primary glial cells of the retina, Kir channels
      are distributed in a highly non-uniform manner, exhibiting high concentrations in
      membrane domains facing the vitreous humor (endfeet) and in proximity to the
      blood vessels (perivascular processes). Such nonuniform distribution of Kir
      channels facilitates directed K+ fluxes in the retina from the synaptic plexiform
      layers to the vitreous humor and blood vessels. Recent molecular and
      electrophysiological studies in Muller cells have revealed a high degree of
      complexity in terms of Kir channel subunit composition, mechanisms of subcellular
      localization, and regulation. How such complexity fits into their proposed role
      in buffering [K+]o in retina is the main topic of this article.

PMID- 14576460
TI  - Acute respiratory distress syndrome.
AB  - Acute respiratory distress syndrome (ARDS) can be associated with various
      disorders. Among these, coronavirus infection may cause life-threatening severe
      acute respiratory syndrome (SARS). In this review, we present animal models and
      techniques for the study of ARDS, and discuss the roles and possible mechanisms
      of various chemical factors, including nitric oxide (NO). Our early work revealed
      that cerebral compression elicits severe hemorrhagic pulmonary edema (PE),
      leading to central sympathetic activation that results in systemic
      vasoconstriction. The consequence of systemic vasoconstriction is volume and
      pressure loading in the pulmonary circulation. Vasodilators, but not oxidant
      radical scavengers, are effective in the prevention of centrogenic PE. In
      isolated perfused lung, exogenous and endogenous NO enhances lung injury
      following air embolism and ischemia/reperfusion. In contrast, NO synthase (NOS)
      inhibitors reverse such lung injury. Although NO is important in maintaining
      vasodilator tone, hypoxia-induced pulmonary vasoconstriction is accompanied by an
      increase instead of a decrease in NO release. In animal and isolated lung
      studies, endotoxin produces acute lung injury that is associated with increases
      in cytokines and inducible NOS mRNA expression, suggesting that NO is toxic to
      the lung in endotoxin shock. Recently, we reported several rare cases that
      indicate that ARDS in patients with Japanese B encephalitis, lymphangitis with
      breast cancer and fat embolism is caused by different mechanisms. Our early and
      recent studies on ARDS and PE may provide information for clinical practice and
      the understanding of the pathogenesis of SARS.

PMID- 14576461
TI  - Transcriptional regulation of CYP11A1.
AB  - Steroid hormones are important physiological regulators that control our glucose
      and salt balance, as well as sexual characteristics. The synthesis of steroid
      hormones is under tight control; disturbed secretion of steroids often leads to
      diseases. The mechanism controlling the secretion of steroids, namely
      steroidogenesis, has been the focus of intensive studies. CYP11A1 controls the
      first and rate-limiting step of steroid biosynthesis. It is expressed in the
      adrenal cortex and gonads, under the control of pituitary hormones, through the
      cAMP-signaling pathway. The promoter of the CYP11A1 gene contains sequences that
      bind to transcription factor SF-1, which plays an important role in the tissue
      specific and hormonally regulated expression of steroidogenic genes. Detailed
      transcriptional analysis documents the importance of SF-1 in activating CYP11A1
      in vitro and in vivo. Other factors like c-Jun are also involved. The assembly of
      various transcription factors forming protein-DNA complexes appears to be the key
      step in CYP11A1 transcription.

PMID- 14576462
TI  - Identification of an endogenous inhibitor of arachidonate metabolism in human
      epidermoid carcinoma A431 cells.
AB  - Eicosanoids, which include prostaglandins, thromboxanes, and leukotrienes, are
      produced from arachidonic acid by three main pathways in cells, including
      cyclooxygenases and lipoxygenases, and cytochrome P450 enzymes. Accumulated
      evidence indicates that a certain peroxide tone is required for the initiation of
      reaction by lipoxygenases and cyclooxygenases. An endogenous inhibitor of
      arachidonate oxygenation was suspected in the cytosolic fraction of human
      epidermoid carcinoma A431 cells. After a series of studies, the existence of this
      inhibitor was confirmed, while it was purified and characterized. By amino acid
      sequence analysis, the inhibitor in A431 cells was subsequently identified as a
      phospholipid hydroperoxide glutathione peroxidase (PHGPx). Depletion of cellular
      glutathione in cells by diethyl maleate or by dibuthionine-sulfoximine results in
      an increase in enzyme activities of 12(S)-lipoxygenase and cyclooxygenase,
      suggesting that glutathione-depleting agents abolish the enzyme activity of PHGPx
      in cells. Stable transfectants of A431 cells with overexpression and depletion of
      PHGPx have been constructed, respectively. Reduction of arachidonate metabolism
      through 12(S)-lipoxygenase and cyclooxygenase 1 and that of the arsenite-induced
      generation of reactive oxygen species are observed in cells overexpressing PHGPx.
      On the other hand, enhancement of arachidonate metabolism and the arsenite
      induced generation of reactive oxygen species is detected in PHGPx-depleted
      cells. In conclusion, the endogenous inhibitor of arachidonate metabolism present
      in A431 cells is a PHGPx, which plays a functional role in the down-regulation of
      arachidonate oxygenation catalyzed by 12(S)-lipoxygenase and cyclooxygenase 1
      through the reduction of the level of intracellular lipid hydroperoxides. The
      latter acts as the peroxide tone for arachidonate metabolism in A431 cells.

PMID- 14576463
TI  - Inhibition of virus replication by RNA interference.
AB  - RNA interference (RNAi) is a sequence-specific gene-silencing mechanism in
      eukaryotes, which is believed to function as a defence against viruses and
      transposons. Since its discovery, RNAi has been developed into a widely used
      technique for generating genetic knock-outs and for studying gene function by
      reverse genetics. Additionally, inhibition of virus replication by means of
      induced RNAi has now been reported for numerous viruses, including several
      important human pathogens such as human immunodeficiency virus type 1, hepatitis
      C virus, hepatitis B virus, dengue virus, poliovirus and influenza virus A. In
      this review, we will summarize the current data on RNAi-mediated inhibition of
      virus replication and discuss the possibilities for the development of RNAi-based
      antiviral therapeutics.

PMID- 14576464
TI  - Identification and functional analysis of truncated human glutamic acid
      decarboxylase 65.
AB  - Human brain glutamate decarboxylase 65 (hGAD65) was found to exist as full-length
      and truncated forms when the glutathione S-transferase-tagged hGAD65 fusion
      protein was subjected to factor Xa cleavage. The truncated form is produced by
      cleavage at arginine 69 based on N-terminal amino acid sequence analysis, and has
      a molecular weight of 58 kD. It is resistant to further factor Xa cleavage or
      mild trypsin treatment and is more active and more stable than the full-length
      form. Both the full-length and truncated forms of GAD are also observed in brain
      preparations in the presence of protease inhibitors. Furthermore, full-length GAD
      could be converted to the truncated form by endogenous proteases, suggesting that
      the conversion of full-length to truncated GAD mediated by endogenous protease
      may represent an important mechanism in the regulation of GABA biosynthesis in
      the brain.

PMID- 14576465
TI  - Overexpression of a novel imprinted gene, PEG10, in human hepatocellular
      carcinoma and in regenerating mouse livers.
AB  - Many of the promising applications of the microarray technology are pertinent to
      identifying abnormalities in gene expression that contribute to malignant
      progression. We developed a bioinformatics tool to identify differentially
      expressed genes in human hepatocellular carcinoma (HCC). This involved the
      construction of a liver EST database (http://lestdb.nhri.org.tw) and in silico
      verification of differentially expressed genes with a human hepatoma microarray
      database. The stringency of the search was reinforced with a statistical
      analysis. A novel imprinted gene, paternally expressed 10(PEG10) was identified
      as having an elevated level of expression in the majority of the HCC samples and
      was also induced to express during G2/M phase of regenerating mouse liver.
      Ectopic expression of PEG10 in 293T cells affects cell cycle progression. PEG10
      is distributed in the cytosol and associates with the nuclear membrane. This is
      the first time that an imprinted gene has been found to reexpress in both human
      HCC and in the regenerating mouse liver. This result indicates that the induction
      of the paternally imprinted gene may play an important role during liver
      regeneration or carcinogenesis of the human hepatocyte. Understanding the
      molecular basis of the abnormal imprinting of PEG10 will shed new light on the
      process that leads to liver disease.

PMID- 14576466
TI  - Large-scale sequencing analysis of the full-length cDNA library of human
      hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is one of the human cancers clearly linked to
      viral infections. Although the major risk factors for HCC development have been
      elucidated, the hepatocellular carcinogenesis pathway resulting in malignant
      transformation of liver cells remains to be clarified. Recently, some results of
      microarray and comparative genomic hybridization analysis have been provided as
      comprehensive studies of genomic instability in HCC, including mutation, deletion
      and DNA copy losses. In this work, the full-length cDNA library has been
      constructed and sequenced, and the sequencing results have been further clustered
      and analyzed. The results show that 1,342 genes have been found, and about 300 of
      these genes may be important in e.g. cell proliferation, DNA repair and
      apoptosis. After further analysis of DNA sequences, the deletion genotypes of at
      least 24 genes have been found. However, the functional changes of these deletion
      mutants and their significance in hepatocellular carcinogenesis remain to be
      clarified. This research may be one of the best to obtain the candidate genes for
      hepatocellular carcinogenesis.

PMID- 14576467
TI  - Cytotoxic T lymphocytes generated by short-term in vitro TCR stimulation in the
      presence of IL-4 are therapeutically effective against B16 melanoma.
AB  - P14 TCR transgenic CD8+ T cells (LCMV gp33-specific) were activated by antigen in
      the presence of either IL-2 or IL-2 + IL-4 to generate effector cytotoxic T
      lymphocytes (CTLs). The therapeutic effectiveness of such IL-2- or IL-2 + IL-4
      grown CTLs was tested in mice that had received intravenous inoculations of
      B16.gp33 melanoma cells 7 days previously. Administration of P14 CTLs activated
      by antigen + IL-2 + IL-4 was significantly more effective at reducing melanoma
      colony formation in the lung than those grown in the presence of antigen + IL-2.
      Highly significant improvement in survival was observed with 80% of B16.gp33
      inoculated mice showing long-term survival after therapy with 10 x 10(6) antigen
      + IL-2 + IL-4-activated P14 CTLs. Similar therapeutic effectiveness of antigen +
      IL-2 + IL-4-activated P14 CTLs against subcutaneously inoculated B16.gp33
      melanoma cells was also found. There was significant reduction in P14 CD8+ T
      cells in the peripheral blood of B16.gp33-inoculated mice than in mice that did
      not receive B16.gp33 melanoma cells, indicating possible homing of P14 CD8+ T
      cells to the site of tumor growth or antigen-induced apoptotic cell death. These
      results may have implications in tumor therapy using CTLs grown ex vivo,
      especially during early stages of tumor formation. They also support the concept
      that the therapeutic effectiveness of CTLs can be governed by the cytokine
      context in which they are activated.

PMID- 14576468
TI  - Requirement for the second coding exon of Tat in the optimal replication of
      macrophage-tropic HIV-1.
AB  - HIV-1 Tat is essential for virus replication and is a potent transactivator of
      viral gene expression. Evidence suggests that Tat also influences virus
      infectivity and cytopathicity. Here, we find that the second coding exon of Tat
      contributes a novel function for the replication/infectivity of macrophage-tropic
      HIV-1. We show that macrophage-tropic HIV-1 which expresses the full-length two
      exon form of Tat replicates better in monocyte-derived macrophages (MDM) than an
      otherwise isogenic virus which expresses only the one-exon form of Tat.
      Similarly, two-exon Tat expressing HIV-1 also replicates better than one-exon Tat
      expressing HIV-1 in two different models of human cells/tissue reconstituted SCID
      mice.

PMID- 14576469
TI  - The significance of clinical signs and blood indices for the diagnosis of
      appendicitis during pregnancy.
AB  - OBJECTIVE: To evaluate the significance of clinical signs and blood indices for
      the diagnosis of appendicitis during pregnancy. SAMPLE: Of the 40,112 women
      delivering at our institution (January 1995 to June 2002), 38 women (0.094%) were
      operated due to the suspicion of appendicitis during pregnancy. METHODS: Body
      temperature, clinical examination, white blood cell counts and lag time from
      arrival to operation were obtained for each patient. All women were operated with
      the clinical diagnosis of appendicitis, and their appendices were removed and
      examined by a pathologist. RESULTS: Inflammatory appendix was discovered in 19
      (0.047%) of the pregnancies with subsequent deliveries while a normal appendix
      was found in 19 of the 38 (50%) appendices removed. The group with normal
      appendix did not significantly differ from women with inflamed appendix with
      regard to gestational age at presentation, signs of peritoneal irritation, body
      temperature, leukocyte count, time elapsed between arrival and surgery,
      gestational age at delivery and birth weight. CONCLUSIONS: The accurate diagnosis
      of appendicitis during pregnancy is a difficult task requiring a very high level
      of suspicion and clinical skills and not merely relying upon laboratory and
      classic signs.

PMID- 14576470
TI  - Modified hysteroscopic myomectomy of large submucous fibroids.
AB  - OBJECTIVE: To compare the efficacy, feasibility, operative time and possible
      complications of a modified technique of hysteroscopic removal of large submucus
      myomata versus traditional morcellation technique, and to assess the efficacy of
      preoperative sonohysterography (SHG). DESIGN: A prospective comparative study.
      SETTING: Gynecologic Endoscopy Unit, Assiut University Hospital, Assiut, Egypt.
      SUBJECTS: One hundred forty-two women of childbearing age with a clinical and
      transvaginal sonographic diagnosis of large solitary submucous myomata (>3 cm in
      diameter) with or without an intramural element. INTERVENTIONS: The patients were
      divided into two groups. In group A (65 patients), a modified resectoscopic
      technique was used where the base of the myoma was excised followed by ring
      forceps extraction after misoprostol priming. In group B (77 patients), the myoma
      was cut using traditional resectoscopic morcellation. MAIN OUTCOME MEASURES: For
      each patient, operating time, intra- and postoperative complications and
      feasibility of the procedure were recorded. The accuracy of preoperative SHG in
      localizing submucous myoma and detecting intramural extension was assessed by
      diagnostic hysteroscopy. RESULTS: Transvaginal SHG showed good agreement with
      hysteroscopy in localizing submucous myomata and detecting intramural extension
      (k = 0.83). The operating time was significantly shorter in group A (15.6 +/-
      3.02 min) than in group B (28.9 +/- 4.3 min). The procedure was completed in 60
      (92%) and 51 patients (66%), whereas a second session was required in 2 (3%) and
      20 patients (25.9%) in both groups respectively. Glycine volume was highly
      significantly less in group A (2.3 +/- 0.86 vs. 6.3+/- 1.7 liters, p = 0.001).
      Intraoperative complications were encountered in 9 (13.8%) and 22 patients
      (28.5%) in both groups respectively (p = 0.03). Cervical laceration was diagnosed
      in 3 cases (4.6%) in group A. Postoperative visual disturbances were diagnosed in
      4 cases (5%) in group B. CONCLUSIONS: Hysteroscopic resection of large submucous
      myomata with minimal intramural encroachment is feasible using a modified
      technique. It shows a minimal complication rate and fluid deficit and a shorter
      operative time than the standard morcellation technique. If the excised myoma is
      extracted as one mass, this carries a minimal risk of cervical lacerations and
      possible cervical incompetence in a subsequent pregnancy. Transvaginal SHG is a
      reliable diagnostic aid to assess submucous myomata.

PMID- 14576471
TI  - Nitric oxide metabolites in preterm and induced labor.
AB  - BACKGROUND: Nitric oxide has potent relaxant effects on the pregnant uterus and
      has been associated with a quiescent uterus in animal and human studies. Nitric
      oxide donors have been used to arrest preterm labor and a reduction in nitric
      oxide production has been reported before the onset of labor. OBJECTIVE: The aim
      of the study was to estimate the serum levels of nitrate and nitrite in women
      undergoing spontaneous preterm labor and induced labor. MATERIALS AND METHOD:
      Venous blood was drawn from 39 patients before the onset of labor (control) and
      also from 17 patients undergoing induction of labor who were in active labor
      (study group A), and 24 patients in spontaneous preterm labor (study group B).
      Serum concentrations of nitrate and nitrite were estimated in the samples using
      the HPLC method. RESULTS: The maternal age of the patients was similar in all the
      groups. There was no significant difference in the mean gestational age at
      delivery between the control and group-A patients (38.86 vs. 38.29 weeks);
      however, there was a significant difference between the control and group-B
      patients (38.86 vs. 30.92; p < 0.0001), and between study groups A and B (38.29
      vs. 30.92 weeks; p < 0.0001). The mean serum levels of nitrite in groups A and B
      (0.563 +/- 0.15 and 0.512 +/- 0.13, respectively) were significantly lower than
      the level in the control group (0.915 +/- 0.13; p < 0.0001). Although the serum
      nitrate levels in study groups A and B were lower than in the control group, this
      difference was not significant. The maternal outcome was satisfactory but, as
      expected, the mean birth weight of the babies in group B (1,665.73 +/- 863.84 g)
      was significantly lower than the birth weights in the control and group-A
      patients (p < 0.0001). CONCLUSION: There is a drop in nitric oxide production in
      active preterm labor and induced labor. These findings need to be confirmed in
      larger studies to establish the role of nitric oxide in the initiation of labor.

PMID- 14576472
TI  - Histopathology and mismatch repair status of 458 consecutive colorectal
      carcinomas.
AB  - Defects in the mismatch repair (MMR) genes hMLH1 and hMSH2 have been found in 10%
      to 20% of sporadic colorectal carcinomas and also many cases of hereditary
      nonpolyposis colorectal cancer syndrome. Patients with these tumors have an
      improved prognosis and may show greater sensitivity to chemotherapy. We examined
      458 resected colorectal carcinomas from 430 consecutive patients and used
      immunohistochemistry to determine which tumors lacked expression of these genes
      (MMR-d). We correlated the status of MMR-d or "intact" expression with stage,
      site, and histology. Eighty-nine of 458 tumors (19.4%) were MMR-d, including 80
      hMLH1 and 9 hMSH2 tumors. A total of 6% of patients had synchronous tumors, and
      37.7% of these were MMR-d (P=0.0008). A high proportion of patients with previous
      breast cancer (4 of 6 patients) had hMLH1-defective colorectal carcinomas. MMR-d
      tumors presented at an earlier stage than intact tumors, and the node-positive
      MMR-d tumors were less likely than intact tumors to have pericolonic extranodal
      tumor deposits (18.2% vs. 44%). The proportion of tumors at each site that were
      MMR-d increased progressively from cecum (32%) to ascending (35%) to transverse
      colon, where 41% of all tumors were defective. The proportions then rapidly
      decreased, reaching the lowest rate (4.7%) in the rectum. Both types of MMR-d
      tumors more often had expansive borders, intraepithelial lymphocytosis,
      peritumoral lymphoid, and Crohn's-like lymphoid responses than the intact tumors;
      the frequencies of these features diminished with advancing stage. Tumor budding
      was less common in stage II and III MMR-d tumors than in intact tumors. Keloid
      and myxoid type stromas correlated with stage and vascular invasion and were not
      related to mismatch repair status. Significant differences existed between the
      hMLH1 and hMSH2 tumors. The reported right-sided preponderance of MMR-d tumors is
      due to most hMLH1, but not hMSH2, tumors being found there (87.5% vs. 44.4%).
      hMSH2 tumors were most common in the rectum (55.6%). Mucinous tumors were common
      in hMLH1 tumors (36.3%) but not in hMSH2 tumors (11.1%). hMLH1 tumors were most
      likely to be poorly differentiated (70%), which was uncommon with hMSH2 tumors
      (22.2%). hMSH2 tumors were more likely to be confined to the wall (66.7%) than
      hMLH1 (20%) or intact tumors (23%). We conclude that hMLH1 and hMSH2-defective
      tumors have distinctly differing histologic features from each other.

PMID- 14576473
TI  - Value of histopathology in predicting microsatellite instability in hereditary
      nonpolyposis colorectal cancer and sporadic colorectal cancer.
AB  - Identification of colorectal carcinomas with high levels of DNA microsatellite
      instability (MSI-H) is important because of the suggested prognostic and
      therapeutic significance associated with MSI. The role of histology in
      identifying MSI-H colorectal carcinomas has been suggested by some studies but
      not confirmed by others. Furthermore, previous studies assumed that hereditary
      nonpolyposis colorectal cancer (HNPCC)-associated MSI-H tumors and sporadic MSI-H
      tumors have similar histology. This assumption, however, has been challenged by
      more recent studies. In this report, we first analyzed the value of various
      histologic features in predicting MSI-H in a series of 218 colorectal carcinomas
      containing mixed HNPCC and sporadic cases [77 tumors (35%) were MSI-H by
      polymerase chain reaction (PCR) method]. Then, we evaluated the various
      histologic features comparatively in two groups extracted from the 218 cases.
      Group A was composed of 84 tumors from 82 patients obtained based on a strong
      family history (HNPCC/HNPCC-like group) (male to female ratio, 42:40; age range,
      23-80 years, median, 53.5 years). Thirty-one of the 84 tumors (41.7%) were MSI-H
      by PCR, and all 31 cases were HNPCC by Amsterdam criteria. Group B was composed
      of 109 patients with no family history of colorectal cancer or HNPCC-associated
      cancer, obtained from surgical clinics (sporadic group) (male to female ratio,
      65:69; age range, 31-84 years, median, 65 years). Thirty-five of the 109 tumors
      (32.1%) were MSI-H by PCR. Our results showed that, overall, poor tumor
      differentiation, medullary type, mucinous type, signet-ring cell component,
      histologic heterogeneity, and increased tumor-infiltrating lymphocytes (TILs)
      were features more commonly seen in MSI-H tumors than in non-MSI-H tumors.
      Comparative analyses showed that the overall TIL count was significantly higher
      in HNPCC/HNPCC-like group, and mucinous type appeared to be more frequent in
      HNPCC MSI-H tumors than in sporadic MSI-H tumors. However, there was no
      significant difference in the odds ratio for predicting MSI-H status for any of
      the analyzed histologic features between HNPCC/HNPCC-like group and sporadic
      group, indicating that differences between HNPCC and sporadic MSI-H tumors did
      not significantly impact on the informative value of histology in predicting MSI
      in the two different clinical settings. TIL counts followed by histologic
      heterogeneity provided the greatest sensitivity and specificity in predicting MSI
      status in both HNPCC/HNPCC-like and sporadic cases. Using a stepwise logistic
      regression model, a formula was generated that could be used to calculate the
      probability of a colorectal carcinoma being MSI-H based on morphologic features.

PMID- 14576474
TI  - Application of mesothelin immunostaining in tumor diagnosis.
AB  - Mesothelin is a differentiation antigen that was first described as the antigenic
      target of the monoclonal antibody K1. Using this antibody, it was demonstrated
      that mesothelin is strongly expressed in normal mesothelial cells, mesotheliomas,
      nonmucinous ovarian carcinomas, and some other malignancies. Immunostaining with
      the K1 antibody was suggested to be useful in the diagnosis of mesothelioma in
      the early 1990s. This, however, could not be further explored until recently
      because of the lack of commercially available anti-mesothelin antibodies. In a
      recent investigation by this author, all epithelioid mesotheliomas and about 40%
      of the lung adenocarcinomas reacted with the 5B2 anti-mesothelin antibody, which
      has only recently become commercially available. It was concluded that
      immunostaining with this antibody has limited value in discriminating between
      these conditions. The aim of the current study was to further investigate the
      potential application of the 5B2 antibody in tumor diagnosis. Mesothelin
      expression was evaluated in formalin-fixed, paraffin-embedded samples of normal
      tissues and in 471 tumors of various origins. The carcinomas that most frequently
      exhibited strong mesothelin reactivity were nonmucinous carcinomas of the ovary
      (14 of 14 serous, 3 of 3 endometrioid, 6 of 8 clear cell, and 4 of 4 transitional
      cell carcinoma), and adenocarcinomas of the pancreas (12 of 14), the ampulla of
      Vater (3 of 3), endometrium (7 of 11), lung (14 of 34), and liver (7 of 19
      cholangiocarcinomas). The carcinomas that did not express mesothelin included
      renal cell carcinomas, hepatomas, carcinomas of the thyroid, adrenal cortical
      carcinomas, prostatic adenocarcinomas, and carcinoid tumors. All germ cell
      tumors, with the exception of teratomas, were consistently negative for
      mesothelin. Because of the strong mesothelin expression in nonmucinous carcinomas
      of the ovary, but not in a variety of tumors with which these lesions may be
      confused (eg, clear cell carcinoma of the ovary versus endodermal sinus tumor or
      renal cell carcinoma, clear cell type; transitional cell carcinoma of the ovary
      versus TCC of the urinary tract), immunostaining for this marker could be useful
      in establishing the differential diagnosis. The strong mesothelin expression in
      the large majority of pancreatic ductal adenocarcinomas (12 of 14), but not in
      normal pancreas, confirms that this marker may have some diagnostic utility in
      discriminating between neoplastic and nonneoplastic pancreatic ductal epithelium.
      The mesothelin expression in about one-third of the cholangiocarcinomas, but not
      in hepatomas, suggests that this marker may have some utility in distinguishing
      between these two malignancies when they are poorly differentiated. In the group
      of small round blue cell tumors, only desmoplastic small round cell tumors
      exhibited mesothelin positivity (7 of 12). Of the soft tissue tumors, only the
      epithelial component of biphasic synovial sarcomas (9 of 9) expressed mesothelin.
      These findings indicate that, in some instances, mesothelin immunostaining can
      assist in the diagnosis of these tumors. Finally, the strong mesothelin
      reactivity seen in the adenomatoid tumors (3 of 3) provides further support for a
      mesothelial derivation for this lesion.

PMID- 14576475
TI  - Signet-ring cell change versus signet-ring cell carcinoma: a comparative
      analysis.
AB  - Signet-ring cell change (SCC) is a nonneoplastic condition that morphologically
      simulates signet-ring cell carcinoma (SRCA). The few case reports on SCC have
      focused on morphologic characteristics in distinguishing benign from malignant.
      In biopsy specimens, however, SCC can be easily confused with SRCA, which often
      demonstrates innocuous cytologic features. The object of this study is twofold:
      1) to report 14 additional cases of SCC, comparing their morphologic and
      phenotypic features with that of SRCA; and 2) to evaluate the incidence of SCC in
      pseudomembranous colitis. Paraffin sections of biopsy or resection specimens
      containing focal or extensive SCC and 5 cases of colonic SRCA were stained with
      hematoxylin and eosin, periodic-acid Schiff stain with and without diastase
      digestion, and by standard ABC immunoperoxidase procedure using antibodies to E
      cadherin, p53, and Ki-67. Both cells in SCC and SRCA were strongly positive for
      neutral mucins. Cells in SCC were strongly positive for E-cadherin and negative
      for p53 and Ki-67. In contrast, cells in SRCA were strongly positive for p53,
      exhibited high proliferation, and demonstrated absent or weak positivity for E
      cadherin. Although SCC is not well recognized in pseudomembranous colitis, the
      incidence is fairly high: 14 of 50 (28%) cases showed variable numbers of signet
      ring cells. Extensive SCC, although rare, can occur in different clinical
      conditions and can be easily mistaken for SRCA. When in doubt, routine
      immunohistochemical stains such as p53, Ki-67, and E-cadherin can help to
      differentiate SCC from SRCA.

PMID- 14576476
TI  - Immunoprofile of ovarian tumors with putative transitional cell (urothelial)
      differentiation using novel urothelial markers: histogenetic and diagnostic
      implications.
AB  - Ovarian tumors containing cells with transitional cell morphology are recognized
      in the 1999 World Health Organization classification of ovarian tumors and
      include benign Brenner tumor, borderline and malignant Brenner tumor, and
      transitional cell carcinoma. Recent immunohistochemical investigations have
      reached conflicting conclusions regarding true urothelial differentiation in
      ovarian Brenner tumors. We evaluated a panel consisting of antibodies to
      uroplakin III (UROIII), thrombomodulin (THR), cytokeratin 7 (CK7), cytokeratin 20
      (CK20), and Wilms' tumor protein (WT1) to study urothelial differentiation in
      ovarian transitional cell tumors. Additionally, we compared the
      immunohistochemical profile of transitional cell carcinoma of the ovary (TCC-O)
      with that of transitional cell carcinoma of the bladder (TCC-B), to ascertain if
      immunohistochemistry may aid in distinguishing primary from metastatic TCC-O.
      Seventeen benign Brenner tumors and 17 TCC-O were stained with antibodies to
      UROIII, THR, CK7, CK20, and WT1. Additionally, 6 Brenner tumors of borderline
      malignancy were stained with antibodies to UROIII, THR, CK7, and CK20. The
      immunohistochemical results were compared with those of 30 cases of noninvasive
      TCC-B (low malignant potential n=14, low grade n=16) and 36 cases of invasive TCC
      B stained with a similar panel of antibodies as part of another study. Twenty-one
      nontransitional cell ovarian carcinomas (9 serous, 4 clear cell, 5 endometrioid,
      2 mixed endometrioid/serous, and 1 mucinous) were used as controls. Most Brenner
      tumors showed positivity with UROIII (82%) and THR (76%), supporting true
      urothelial differentiation in these tumors. Although TCC-O has considerable
      morphologic overlap with TCC-B, they had only partial immunophenotypic overlap.
      TCC-O rarely expressed UROIII (6%) and THR (18%) and none expressed CK20. In
      contrast, nearly 40% of invasive TCC-B expressed UROIII, 61% expressed THR, and
      50% expressed CK20. Nearly 82% of TCC-O expressed WT1, which was negative in all
      TCC-B. Our results may have diagnostic value in distinguishing TCC-O (CK20-,
      UROIII-/+, WT1+) and invasive TCC-B (CK20+, UROIII+/-, WT1-) metastatic to the
      ovary. They also indicate that the morphologic similarity between TCC-O and TCC-B
      does not indicate any histogenic similarity and, as others have noted, TCC-O is a
      variant morphology in the spectrum of surface epithelial carcinomas.

PMID- 14576477
TI  - Cdx2 as a marker of epithelial intestinal differentiation in the esophagus.
AB  - The histologic diagnosis of Barrett's esophagus requires the presence of goblet
      cells, but this finding may not be the earliest indicator of intestinal
      metaplasia. We used immunohistochemistry to detect Cdx2, a transcriptional
      regulator important in the early differentiation and maintenance of intestinal
      epithelium, in 134 esophageal biopsy or resection specimens, including 62 with
      junctional-type epithelium (13 of which had equivocal histologic features of
      Barrett's epithelium), 34 with Barrett's epithelium without dysplasia, and 38
      with Barrett's epithelium and dysplasia or carcinoma (13 low-grade dysplasias, 19
      high-grade dysplasias, and 6 adenocarcinomas). We also performed PAS-alcian blue
      staining (pH 2.5) on adjacent sections. Cdx2 was observed in all cases of
      Barrett's epithelium. In some dysplasias (chiefly high-grade) and
      adenocarcinomas, there was diminution or focal loss of detectable protein. Cdx2
      was detected in 20 of 62 cases (30%) of junctional-type epithelium, including 10
      of 13 (77%) with equivocal histologic features of Barrett's epithelium. Acid
      mucin was present in goblet cells and non-goblet columnar cells in all cases of
      Barrett's esophagus and in non-goblet columnar cells in 48 of 62 cases (77%) with
      junctional-type epithelium only, including 17 of 20 (85%) that were Cdx2 positive
      and 31 of 42 (74%) that were Cdx2 negative. These results provide evidence that
      Cdx2 protein is a sensitive marker of intestinal metaplasia in the upper
      gastrointestinal tract and may be useful in detecting histologically equivocal
      cases of Barrett's esophagus. Cdx2 is present in dysplasia and adenocarcinoma,
      with some loss of protein primarily in high-grade dysplasia and adenocarcinoma.
      Acid mucin in non-goblet columnar cells is a common feature of Barrett's and
      junctional-type epithelium and may not always be indicative of intestinal
      metaplasia.

PMID- 14576478
TI  - Lichen sclerosus in 68 patients with squamous cell carcinoma of the penis:
      frequent atypias and correlation with special carcinoma variants suggests a
      precancerous role.
AB  - Lichen sclerosus, an unusual chronic mucocutaneous condition of the penis, has
      been found in association with invasive penile cancer, and squamous cell
      carcinoma has been reported in patients with longstanding lichen sclerosus. The
      aim of this study was to determine the anatomic distribution and prevalence of
      lichen sclerosus in patients with squamous cell carcinoma of the penis and to
      search for a correlation with special types of carcinomas. Clinical and
      pathologic data from 207 penectomy and circumcision specimens with squamous cell
      carcinomas and giant condylomas were evaluated, and 68 patients with lichen
      sclerosus were identified. Mean age was 61 years. The preferential anatomic site
      of lichen sclerosus was the foreskin, but other sites (glans and coronal sulcus)
      including urethra were also involved. Grossly, the lesions showed white-gray
      smooth or irregular patches and plaques adjacent to invasive cancers.
      Microscopically, the lesion was stromal-epithelial with atrophic and hyperplastic
      epithelium and edematous or densely eosinophilic hyalinized lamina propria. A
      variable band of lymphocytic infiltration beneath the sclerosis was noted. Lichen
      sclerosus were preferentially associated with non-human papillomavirus variants
      of squamous cell carcinoma. When lichen sclerosus was associated with malignancy,
      it often showed, in addition to the hyperplastic epithelium, a low-grade squamous
      intraepithelial lesion. These findings suggest that lichen sclerosus may
      represent preneoplastic condition for at least some types of penile cancers, in
      particular those not related to human papillomavirus.

PMID- 14576479
TI  - Bile ducts and ductules are positive for CD56 (N-CAM) in most cases of
      extrahepatic biliary atresia.
AB  - The diagnosis of extrahepatic biliary atresia can be challenging as the
      histologic features can overlap with other pediatric cholestatic liver diseases.
      Several previous studies have noted that biliary epithelium is positive for CD56
      in the setting of extrahepatic biliary tract disease. Thus, we explored the use
      of CD56 in evaluating liver biopsy specimens for extrahepatic biliary atresia. A
      total of 22 cases were selected and immunostained for CD56, including 14 cases of
      confirmed extrahepatic biliary atresia and 8 cases of other cholestatic liver
      diseases in which the differential diagnosis included extrahepatic biliary
      atresia. Bile ducts and proliferating ductules were positive for CD56 in 13 of 14
      cases of extrahepatic biliary atresia. The staining intensity was generally
      strong with most cases showing positivity in more than two thirds of portal
      tracts. The one negative case was a very small biopsy (<0.3 cm), and sampling may
      have played a role. In contrast, 4 of 8 cases in the control group were
      completely negative for CD56, with the remaining cases showing weak and focal
      positivity. In conclusion, bile ducts and ductules are CD56 positive in most
      cases of extrahepatic biliary atresia, and CD56 immunostaining can be a useful
      supplemental stain for diagnosing extrahepatic biliary atresia in its early,
      ductular proliferative phase when used in conjunction with traditional
      hematoxylin and eosin morphology and clinical information.

PMID- 14576480
TI  - Use of oxytocin receptor expression in distinguishing between uterine smooth
      muscle tumors and endometrial stromal sarcoma.
AB  - The present study aimed to investigate oxytocin receptor (OTR) expression in the
      normal uterus, and particularly in uterine smooth muscle tumors and endometrial
      stromal sarcomas (ESSs) because these tumors can be difficult to distinguish. The
      expressions of OTR, CD10, h-caldesmon, calponin, smooth muscle actin, and desmin
      were analyzed in 10 conventional leiomyomas (LMs), 10 highly cellular leiomyomas
      (HCLs), eight leiomyosarcomas (LMSs), and nine ESSs. In five normal uteri and
      five cases of adenomyosis, OTR was strongly expressed in the myometrium and
      showed expression pronounced in the surface epithelium during the late
      proliferative phase and at the time of ovulation, whereas the endometrial stromal
      cells were negative. All LMs and HCLs were strongly positive for OTR. Five cases
      of LMS showed moderate to strong OTR expression in 100% of the tumor cells,
      whereas three cases were weakly positive in 10-20% of the tumor cells. Every ESS
      was negative for OTR, except in regions of smooth muscle differentiation. All
      ESSs were positive for CD10, as were one LM, six HCLs, and five LMSs. The ESSs
      were negative for h-caldesmon and showed desmin positivity mainly in regions of
      smooth muscle metaplasia. h-Caldesmon, calponin, smooth muscle actin, and desmin
      were expressed in all LMs, HCLs, and LMSs except for one leiomyosarcoma with
      epithelioid features, which was negative for h-caldesmon and calponin. Our study
      indicates that the evaluation of OTR expression is useful in the distinction of
      uterine smooth muscle tumors from ESSs, and that the OTR is expressed in normal
      and neoplastic uterine smooth muscle cells.

PMID- 14576482
TI  - Bottoms up to a Nobel-worthy chicken's bottom.

PMID- 14576481
TI  - Prevalence of human papillomavirus type 16 DNA in squamous cell carcinoma of the
      palatine tonsil, and not the oral cavity, in young patients: a distinct
      clinicopathologic and molecular disease entity.
AB  - Squamous cell carcinoma of the head and neck commonly affects patients in their
      sixth decade and older, particularly those with a prolonged history of alcohol
      and tobacco abuse. Less frequently, carcinomas occur in young individuals even in
      the absence of known risk factors. The purpose of this study is to investigate a
      possible relationship between these tumors and human papilloma virus (HPV).
      Thirty-three cases of squamous cell carcinoma of the head and neck in young
      patients under the age of 40 years were studied: 15 oral, 11 tonsillar, and 7
      laryngeal. HPV DNA was detected by polymerase chain reaction in 10 tonsillar and
      2 laryngeal carcinomas and in none of the oral tumors. Of the 12 HPV-positive
      tumors, 11 were HPV16 and 1 was HPV31. HPV-positive tumors had a distinct
      nonkeratinizing basal cell morphology, they stained diffusely and strongly with
      p16 antibodies, had higher Ki-67 and lower p53 staining scores as compared with
      the conventional keratinizing HPV negative carcinomas. It is concluded that in
      young patients high-risk HPV, particularly HPV16, is strongly associated with
      tonsillar squamous cell carcinoma and some cases of laryngeal, but not oral,
      tumors. The HPV-positive carcinomas have a distinct histopathologic and
      immunophenotypic features.

PMID- 14576483
TI  - A case of a diffuse large B-cell lymphoma of plasmablastic type associated with
      the t(2;5)(p23;q35) chromosome translocation.
AB  - Anaplastic large cell lymphomas are associated with the t(2;5)(p23;q35)
      chromosome translocation in 40% to 60% of cases, leading to a new chimeric gene
      NPM-ALK. NPM-ALK positive lymphomas are generally reported to be of either T cell
      or null phenotype. In this report, we describe a diffuse large B-cell lymphoma
      associated with the classic t(2;5) translocation and both nuclear and cytoplasmic
      expression of ALK. The tumor consisted of medium-sized to large immunoblasts and
      plasmablasts that on immunohistology were negative for CD30, CD20, and CD79a but
      showed monotypic cytoplasmic expression of lambda light chains. Clonality
      analysis confirmed B-cell lineage of the tumor cells. The t(2;5)(p23;q35)
      chromosome translocation was demonstrated as part of a complex karyotypic
      alteration by classic banding and spectral karyotyping (SKY) analyses. Reverse
      transcription polymerase chain reaction confirmed rearrangement of NPM and ALK
      genes. This case exemplifies that the t(2;5) can, albeit rarely, occur in large B
      cell lymphomas and is not entirely limited to anaplastic large cell lymphomas of
      T or null cell phenotypes.

PMID- 14576484
TI  - Metachronous development of nonamyloidogenic [lambda] light chain deposition
      disease and IgG heavy chain amyloidosis in the same patient.
AB  - We report a highly unusual case of monoclonal immunoglobulin deposition disease
      associated nephrotic syndrome in which a patient developed both lambda light
      chain deposition disease and 6 years afterward IgG-heavy chain amyloidosis. The
      patient initially underwent autologous peripheral blood stem cell transplantation
      as treatment of the underlying plasma cell dyscrasia causing the light chain
      deposition disease-related nephrotic syndrome. After 6 years of clinical
      remission, recurrence of the nephrotic syndrome led to a renal biopsy
      demonstrating IgG-heavy chain amyloidosis. Interestingly, much of the
      characteristic nodular glomerular sclerosis seen in light chain deposition
      disease regressed between the time of the first biopsy and the second. Given the
      length of time between the development of the two diseases and the apparent
      success of stem cell transplantation in treating the first, we think that the
      patient produced two distinctly different abnormal plasma cell clones. To our
      knowledge, this is the first report of two different monoclonal immunoglobulin
      deposition diseases occurring in the same patient.

PMID- 14576485
TI  - Analysis of a clonally related mantle cell and Hodgkin lymphoma indicates Epstein
      Barr virus infection of a Hodgkin/Reed-Sternberg cell precursor in a germinal
      center.
AB  - The simultaneous occurrence of a Hodgkin lymphoma (HL) and a non-Hodgkin lymphoma
      (NHL) is a rare event, and single cell analyses of such composite lymphomas
      revealed that NHL and Hodgkin/Reed-Sternberg (HRS) tumor cells are frequently
      descendants of the same tumor clone precursors. Here we present a composite
      lymphoma consisting of a mantle cell lymphoma (MCL) and an HL with EBV- and EBV+
      HRS cells. Analysis of rearranged V genes of single cells revealed a clonal
      relationship between MCL and HL tumor cells. Although V gene rearrangements of
      the MCL were unmutated, mutations were observed in HRS cells. Besides mutations
      shared by all HRS cells, the EBV+ HRS cells carried identical additional
      mutations. These findings show that both lymphomas derive from a common
      precursor, most likely a pre germinal center (GC) B cell that already carried
      some transforming event(s). However, the presence of mutations in the V genes of
      the HRS cells further corroborates the importance of the GC reaction for the
      pathogenesis of HL. Importantly, the finding that only a subclone of the HRS
      clone, defined by a particular mutation pattern, was EBV infected represents a
      strong indication that EBV infection of the HRS cell precursor happened in the
      GC.

PMID- 14576487
TI  - Mechanisms of alcoholic pancreatitis. Proceedings of a conference. Chicago,
      Illinois, USA, November 2002.
AB  - Long-term, heavy alcohol consumption is associated with both acute and chronic
      pancreatitis. Progression of pancreatitis may lead to multiple comorbidities
      including maldigestion, diabetes, and pancreatic cancer. Understanding the
      underlying molecular, biochemical, and cellular mechanisms by which alcohol
      ingestion leads to the development of pancreatitis may help to develop strategies
      for the treatment and prevention of the disease. The National Institute on
      Alcohol Abuse and Alcoholism and the Office of Rare Diseases of National
      Institutes of Health sponsored a satellite symposium on "Mechanisms of Alcoholic
      Pancreatitis" at the annual meeting of the American Pancreatic Association,
      Chicago, IL, November 2002. For this symposium, 8 speakers were invited to
      address the following issues: (1) epidemiology of alcoholic pancreatitis; (2)
      pathophysiology of alcoholic pancreatitis; (3) animal models of alcoholic
      pancreatitis--roles of cholecystokinin (CCK) and viral infections; (4) alcohol
      and zymogen activation in the pancreatic acinar cell; (5) role of alcohol
      metabolism in alcoholic pancreatitis; (6) pancreatic stellate cell activation in
      alcoholic pancreatitis; and (7) genetic predisposition to alcoholic chronic
      pancreatitis. It was concluded that alcohol abuse is a major contributory factor
      to the development of both acute and chronic pancreatitis. The injurious effects
      of ethanol on the pancreas may be mediated through (1) sensitization of acinar
      cells to CCK-induced premature activation of zymogens; (2) potentiation of the
      effect of CCK on the activation of transcription factors, nuclear factor kappaB
      (NF-kappaB) and activating protein-1 (AP-1); (3) generation of toxic metabolites
      such as acetaldehyde and fatty acid ethyl esters; (4) sensitization of the
      pancreas to the toxic effects of coxsackievirus B3; and (5) activation of
      pancreatic stellate cells by acetaldehyde and oxidative stress and subsequent
      increased production of collagen and other matrix proteins.

PMID- 14576486
TI  - Neoplasms derived from plasmacytoid monocytes/interferon-producing cells:
      variability of CD56 and granzyme B expression.

PMID- 14576488
TI  - The epidemiology of alcohol-induced pancreatitis.
AB  - Although the association between alcohol and pancreatitis has been recognized for
      centuries, the precise magnitude of the impact of alcohol remains poorly
      quantified. Epidemiologic research on this condition has been seriously
      handicapped by several factors. Classifications are based on morphology rather
      than on etiology; the diagnostic differences between acute and chronic
      pancreatitis are imprecise and confusing; and coding by the International
      Classification of Diseases (ICD) has been inadequate. The current ICD (ICD-10),
      used in the United States since 1999, identifies alcohol-induced chronic
      pancreatitis as a separate code for the first time, an enhancement that will
      greatly improve the quality of data collected in current and future studies.
      Unfortunately, no code yet exists for acute alcoholic pancreatitis. Of the
      approximately 2.4 million deaths in the United States in 1999, pancreatitis was
      listed as the underlying cause for 3289 deaths, making it the 235th leading cause
      of death. Acute pancreatitis accounted for 84% of these deaths, and chronic
      pancreatitis the remaining 16%. Alcohol is a primary cause of both acute and
      chronic pancreatitis in most developed countries. About one-third of acute
      pancreatitis in the United States is alcohol-induced. In the United States and
      other developed countries, 60%-90% of chronic pancreatitis is alcohol induced.
      Both forms are more common in men. The development of chronic pancreatitis is
      proportional to the dose and duration of alcohol consumption (minimum, 6-12 years
      of approximately 80 g of alcohol per day). Autopsy studies reveal subclinical
      chronic pancreatitis in another 10% of alcohol abusers. Yet, since <10% of
      chronic alcoholics develop chronic pancreatitis, clearly other predisposing
      factors besides alcohol are involved. Genetic variability and environmental
      exposures, such as diet, are prime candidates for further investigation. To date,
      there have been few large epidemiological studies of alcoholic pancreatitis in
      the United States or other developed countries. Additional studies are needed to
      improve the quality of existing baseline epidemiologic data and allow better
      assessment of risk. Improved diagnostic precision, more complete and specific
      coding, and greater understanding of covariables and mechanisms would also
      advance the field.

PMID- 14576489
TI  - Pathophysiology of alcohol-induced pancreatitis.
AB  - Excessive ethanol consumption is a common risk factor for acute and chronic
      pancreatitis. Ethanol could lead to the onset of pancreatitis in a number of
      ways; the most recently discovered is its effect on intrapancreatic digestive
      enzyme activation, by either sensitizing acinar cells to pathologic stimuli or
      stimulating the release of a secretagogue (cholecystokinin) from duodenal I
      cells. Recent advances in cell biologic and molecular techniques have permitted
      us to address the intracellular events involved in digestive enzyme activation in
      a manner that was previously considered impossible. Investigations that used
      these novel techniques found that (a) trypsin is, in contrast to its role in the
      small intestine, not necessarily involved in the premature intracellular
      activation of other digestive proteases such as proelastase; (b) trypsinogen does
      not autoactivate intracellularly but is instead largely activated by the
      lysosomal hydrolase cathepsin B; and (c) the role of trypsin in the
      intrapancreatic protease cascade is most likely one that involves the
      degradation, rather than the activation, of active digestive proteases including
      trypsin itself. These studies, as well as investigations that have addressed the
      role of mutant trypsin in the disease onset of hereditary pancreatitis, suggest
      that trypsin may not be critical for triggering pancreatitis but might have a
      protective role against the action of some of the other digestive proteases.
      While the specific role of different digestive enzymes in initiating pancreatitis
      is still a matter of debate and the topic of ongoing investigations, experimental
      evidence suggests that ethanol can directly interfere with the processes involved
      in digestive zymogen activation.

PMID- 14576490
TI  - Animal and in vitro models of alcoholic pancreatitis: role of cholecystokinin.
AB  - Although ethanol abuse is the major etiologic factor in the development of acute
      and chronic pancreatitis, the mechanisms of ethanol effects to cause pancreatitis
      are poorly understood. The major reason for the lack of progress is the relative
      lack of animal models that reproduce the deleterious effects of ethanol on the
      pancreas that are observed in human disease. We propose that the effect of
      ethanol on the pancreas is due to its ability to sensitize animals and humans to
      the potentially injurious effects of other stimuli. We have developed models of
      ethanol-induced acute and chronic pancreatitis in rats as well as pancreatic
      acinar cells in primary culture demonstrating that ethanol sensitizes the
      pancreas to the inflammatory, cell death, and fibrosing responses caused by
      cholecystokinin (CCK). Our results indicate that the ethanol-sensitized
      inflammatory response is the key or trigger event for the development of the
      other pathologic responses in both acute and chronic pancreatitis, such as cell
      death, intracellular digestive enzyme activation, and fibrosis. These findings
      suggest that experimental strategies designed to reveal the modulating effects of
      ethanol on the mechanisms underlying the inflammatory, cell death, and fibrosing
      responses stimulated by CCK will provide the key information needed to understand
      how ethanol abuse causes pancreatitis.

PMID- 14576491
TI  - Animal model of alcoholic pancreatitis: role of viral infections.
AB  - Pancreatitis is clearly associated with alcohol abuse, but only a relatively
      small percentage of people who abuse alcohol develops obvious pancreatitis. These
      observations have led to the concept that the development of alcoholic
      pancreatitis requires cofactors. Although diet and smoking have been studied, a
      clear cofactor has not been identified. The study results presented in this paper
      were obtained to determine whether viral infection of the pancreas would be a
      cofactor for alcoholic pancreatitis similar to the role of hepatitis virus
      infections in the development of alcoholic liver disease. To test this
      hypothesis, mice were fed ethanol with a liquid diet protocol and infected with
      coxsackievirus B3 (CVB3). It was found that consumption of alcohol alone did not
      result in pancreatitis as determined by serum levels of amylase or histologic
      changes in the pancreas. Two strains of CVB3 that are tropic for the pancreas
      were used; a virulent and an avirulent strain. Infection of alcohol-fed animals
      with the virulent CVB3 strain 28 resulted in a more severe pancreatitis than the
      pancreatitis noted in control animals. Alcohol-fed mice infected with the
      avirulent strain (GA) showed severe pancreatitis, whereas the infection of
      control mice did not result in obvious pathologic effects in the pancreas. This
      model allows mechanistic studies to define the role of viral infection as a
      cofactor for alcoholic pancreatitis.

PMID- 14576492
TI  - Alcohol and zymogen activation in the pancreatic acinar cell.
AB  - SUMMARY: Activation of zymogens within the pancreatic acinar cell is an early
      feature of acute pancreatitis. Supraphysiologic concentrations of cholecystokinin
      (CCK) cause intrapancreatic zymogen activation and pancreatitis. Supraphysiologic
      concentrations of CCK also cause zymogen activation in isolated pancreatic acini.
      This activation first occurs in a nonzymogen granule compartment that contains
      lysosomal markers. A low pH environment may also be needed for activation. To
      examine the ability of alcohols to sensitize the acinar cell to CCK, the
      conversion of zymogens to active enzymes in isolated acini was assayed. Alcohols,
      including 35 mmol/L ethanol, sensitized acini to CCK induced activation. The
      sensitization increased with chain length and was less in branched compared with
      unbranched alcohols. The relationship of alcohol's structure to sensitization may
      be related to the mechanism of sensitization.

PMID- 14576493
TI  - Role of alcohol metabolism in alcoholic pancreatitis.
AB  - Metabolism of ethanol by acinar and other pancreatic cells and the consequent
      generation of toxic metabolites are postulated to play an important role in the
      development of alcohol-related acute and chronic pancreatic injury. Studies using
      cultured pancreatic acinar cells and isolated pancreatic acini have established
      that (i) the pancreas can metabolize ethanol via the oxidative pathway involving
      the enzymes alcohol dehydrogenase (ADH) and possibly cytochrome P4502E1 (although
      the role of the latter remains to be fully delineated) as well as the
      nonoxidative pathway [involving fatty acid ethyl ester (FAEE) synthases] and (ii)
      the oxidative pathway (which generates acetaldehyde) is quantitatively greater
      than the nonoxidative pathway, which yields FAEEs. Most recently, pancreatic
      stellate cells (PSCs) (implicated in pancreatic fibrogenesis) have been reported
      to exhibit ADH activity, suggesting that the capacity of the pancreas to
      metabolize ethanol may reside not only in parenchymal (acinar) cells but also in
      nonparenchymal cells. Polymorphisms/mutations of ethanol metabolizing enzymes
      have been examined to determine whether they may confer individual susceptibility
      to alcoholic pancreatitis. However, no association has been demonstrated between
      ADH and CYP2E1 polymorphisms and the predisposition to alcoholic pancreatitis.
      Other candidate factors that remain to be studied include polymorphisms of FAEE
      synthetic enzymes and proteins relevant to antioxidant pathways in the cell.
      Injury to the pancreas due to its capacity to metabolize ethanol may be mediated
      by direct effects of both acetaldehyde and FAEEs and by alterations induced
      within the cells during ethanol metabolism, such as changes in the intracellular
      redox state and the generation of oxidant stress.

PMID- 14576494
TI  - Stellate cell activation in alcoholic pancreatitis.
AB  - The pathogenesis of pancreatic fibrosis, a characteristic feature of alcohol
      induced chronic pancreatitis, has received increasing attention over the past few
      years, largely due to the identification and characterization of stellate cells
      in the pancreas. These cells are morphologically similar to hepatic stellate
      cells, the principal effector cells in liver fibrosis. The role of pancreatic
      stellate cells (PSCs) in alcoholic pancreatic fibrosis has been studied using 2
      approaches: (i) in vivo studies using pancreatic tissue from patients with
      alcohol-induced chronic pancreatitis and from animal models of experimental
      pancreatitis and (ii) in vitro studies using cultured PSCs. These studies
      indicate that PSCs are activated early in the course of pancreatic injury and are
      the predominant source of collagen in the fibrotic pancreas. Several factors that
      may be responsible for mediating PSC activation during chronic alcohol exposure
      have also been identified. From the findings to date, it may be speculated that
      the pathogenesis of alcoholic pancreatic fibrosis may involve 2 pathways: (i) a
      necroinflammatory pathway involving cytokine release and PSC activation and (ii)
      a nonnecroinflammatory pathway involving direct activation of PSCs by ethanol via
      its metabolism to acetaldehyde and the generation of oxidant stress.

PMID- 14576495
TI  - Genetic predisposition to alcoholic chronic pancreatitis.
AB  - The mechanisms leading to alcoholic chronic pancreatitis in humans have remained
      elusive. Numerous questions surround the apparent random nature of the disease in
      which 1 person is hit with alcoholic chronic pancreatitis while the next is
      spared. Why do fewer than 10% of chronic, heavy alcohol users ever develop
      pancreatitis, while others develop alcoholic liver disease, neuropathy, or other
      alcohol-associated problems? Why do laboratory animals, fed large amounts of
      alcohol for prolonged periods of time, fail to develop typical chronic
      pancreatitis? Why are heavy alcohol users from a black African background more
      likely to develop pancreatic diseases than Caucasians, whereas the opposite is
      true for the development of liver disease? The answers underlying these questions
      appear to reflect the differences in underlying genetic susceptibility,
      environmental exposure, and the interaction between these factors. Thus, even
      cases of "typical" alcoholic chronic pancreatitis or other forms of pancreatitis
      appear to be complex diseases. Recently, several genetic mutations have been
      identified that increase the susceptibility to pancreatitis. However, the major
      common gene mutations in CFTR, PRSS1, and SPINK1 only slightly increase the risk
      of alcoholic chronic pancreatitis. New genetic, environmental, and triggering
      factors must be considered to gain further insight into the mechanisms leading to
      alcoholic chronic pancreatitis so that strategies for treatment and prevention
      can be developed.

PMID- 14576496
TI  - Pathophysiology of alcohol-induced pancreatic injury.
AB  - The evidence that ethanol abuse can lead to pancreatitis is overwhelming, but the
      mechanism(s) by which ethanol causes pancreatic injury and pancreatitis are not
      known. Many studies have focused on short-term effects of ethanol administration
      on exocrine pancreatic function, but the results reported have been variable and
      no clear picture has emerged. Attempts to induce pancreatitis by long-term
      ethanol administration have, for the most part, failed. We evaluated the effects
      of ethanol administration on pancreatic secretion of digestive enzymes. These
      studies indicate that administration of ethanol results in a transient increase
      in pancreatic amylase output and plasma cholecystokinin (CCK) levels. This
      phenomenon is mediated by a trypsin-sensitive CCK-releasing factor that is
      present within the duodenal lumen. These observations lead us to speculate that
      repeated CCK-mediated, ethanol-induced stimulation of pancreatic digestive enzyme
      secretion may play a role in the events that link ethanol abuse to the
      development of pancreatic injury.

PMID- 14576497
TI  - Mutations of the CFTR gene in pancreatic disease.
AB  - INTRODUCTION: An association has been found between CFTR gene mutations and
      chronic pancreatitis; however, there is a lack of information about the frequency
      of CFTR gene mutations in acute pancreatitis and in pancreatic cancer. AIM: To
      prospectively evaluate the prevalence of CFTR gene mutations in acute
      pancreatitis, chronic pancreatitis, and pancreatic cancer. METHODOLOGY: Ninety
      eight consecutive patients were studied and divided into 3 groups: 34 patients
      with acute pancreatitis, 46 patients with chronic pancreatitis, and 18 patients
      with pancreatic cancer. The mutation analysis of the CFTR gene was carried out
      using diagnostic commercial kits for the simultaneous detection of 29 mutations
      and Tn polymorphism. RESULTS: Among the 98 patients studied, 12 (12.2%) had CFTR
      gene mutations: 2 of the 34 patients (5.9%) with acute pancreatitis, 9 of the 46
      (19.6%) with chronic pancreatitis, and 1 of the 18 (5.6%) with pancreatic cancer.
      All the mutations were found in heterozygosis (2 DeltaF508, 1 W1282X, and 9 T5
      allele). CONCLUSION: Our prospective study adds further information about the
      frequency of CFTR mutations in patients with a single episode of acute
      pancreatitis. Furthermore, our results suggest an association of CFTR gene
      mutations with chronic alcoholic pancreatitis and emphasize the need for a
      multicenter study, possibly multinational, to conclusively establish the role of
      CFTR mutations as a genetic susceptibility factor for this disease.

PMID- 14576498
TI  - MEK inhibition of pancreatic carcinoma cells by U0126 and its effect in
      combination with sulindac.
AB  - OBJECTIVES: The MAP kinase kinase (MEK)-extracellular signal-regulated kinase
      (ERK) pathway is critical for cell growth and survival. In the current study, we
      examined the effect of inhibiting the MEK-ERK pathway in pancreatic tumor cells
      with the MEK-specific inhibitor U0126. In addition, we investigated whether the
      MEK-ERK pathway influenced the response of pancreatic cancer cells to
      nonsteroidal antiinflammatory drugs (NSAIDs). METHODS: Cell growth was monitored
      by a colorimetric proliferation assay and cell counts. Cell cycle analysis was
      performed using flow cytometry. Apoptosis was measured using a DNA fragmentation
      ELISA. Protein expression was detected by Western blot. CONCLUSION: Treatment
      with U0126 dose dependently inhibited the growth of 3 human pancreatic carcinoma
      cell lines (BxPC-3, PANC-1, and MIA PaCa-2). U0126 treatment resulted in cell
      cycle alterations but did not induce apoptosis. Growth inhibitory concentrations
      of NSAIDs unexpectedly increased ERK phosphorylation in BxPC-3 and MIA PaCa-2
      cells. We therefore evaluated the effect of treating pancreatic tumor cells with
      the combination of the NSAID sulindac and U0126. Treatment with U0126
      complemented sulindac-induced growth inhibition in BxPC-3 and PANC-1 cells. The
      expression of several cell cycle (p21, p27, cyclin D1) and apoptotic (survivin,
      Bcl-xL) regulatory proteins was altered after U0126 and/or sulindac treatment.
      Our findings suggest that inhibition of the MEK-ERK signaling pathway may
      sensitize pancreatic tumor cells to NSAID therapy.

PMID- 14576499
TI  - Analysis of expression profiles of islet-associated transcription and growth
      factors during beta-cell neogenesis from duct cells in partially duct-ligated
      mice.
AB  - INTRODUCTION: Beta-cell neogenesis from pancreatic duct cells has been reported
      to occur in duct-ligated rat. Nevertheless, detailed process of this phenomenon
      has not been clarified. AIMS AND METHODOLOGY: To clarify the mechanism of beta
      cell neogenesis, a partial pancreatic duct ligation mouse model was created.
      Proliferation of duct cells, beta-cell neogenesis, and expression of
      transcription factors and differentiation/growth factors were studied by
      immunohistochemistry, cDNA array, and RT-PCR methods. RESULTS: In the duct
      ligated portion of the pancreas, newly formed islet-like cell clusters (ICCs)
      were observed arising from the ducts on day 7 and afterward. Transcription
      factors, such as pancreatic and duodenal homeobox gene-1 (PDX-1), paired box
      factor 6 (Pax6), islet1 and Nkx2.2-positive cells, and protein gene product 9.5
      (PGP9.5) were also induced in duct lining cells. By cDNA microarray analysis,
      expression of insulin-like growth factor-1 (IGF-1) and transforming growth factor
      beta1 (TGF-beta1) were above control levels on day 5, and RT-PCR showed an
      increase from day 5 to day 28. IGF-1 and activin A-positive cells were detected
      in ducts. In addition, expression of betacellulin (BTC), heparin-binding
      epidermal growth factor-like growth factor (HB-EGF), and TGF-alpha were also
      increased from day 3 or 5. CONCLUSION: These findings suggest that beta-cell or
      endocrine precursors are localized among duct lining cells. Induction of several
      islet cell-associated transcription factors and differentiation and/or growth
      factors may play important roles during beta-cell neogenesis in this model.

PMID- 14576500
TI  - Nutritional links to plausible mechanisms underlying pancreatic cancer: a
      conference report.
AB  - Adenocarcinoma of the pancreas is one of most catastrophic and least understood
      of cancers. Evidence from clinical studies indicates that the development of
      pancreas cancer progresses over many years before symptoms appear. Most people
      with pancreatic cancer die within six months of diagnosis. The lack of early
      disease markers, the paucity of direct subject/patient interview data and limited
      availability of high quality biological samples have slowed progress toward
      identifying environmental and genetic disease risk factors. Much remains to be
      learned about the development of pancreatic cancer and about potential
      interventions for disease prevention. Epidemiological and mechanistic studies
      examining risk factors for pancreatic cancer supply little consistent or strong
      evidence to provide a cohesive prevention strategy for this cancer, but offer
      clues for future research concerning the prevention and early detection of this
      devastating disease. This Executive Summary provides background discussion on
      pancreatic cancer and summaries of each of the topics discussed at the workshop,
      including 1) Molecular aspects, 2) Dietary and other risk factors for pancreatic
      cancer, 3) The metabolic hypothesis for pancreatic cancer, 4) Preclinical studies
      on pancreatic cancer, 5) Methylation, 6) Oxidative stress and 7) Biomarker
      Profiling. This document also contains a compilation of recommendations for
      future research, concluding remarks, a list of speakers and participants
      attending the workshop, and a selection of key references to aid future research
      into nutritional links to mechanisms underlying pancreas cancer. The
      recommendations section suggests gaps in current knowledge and articulates future
      directions for this area of investigation.

PMID- 14576501
TI  - Prophylaxis with meropenem of septic complications in acute pancreatitis: a
      randomized, controlled trial versus imipenem.
AB  - OBJECTIVES: Prophylactic antibiotics are helpful in decreasing the incidence of
      septic complications in acute pancreatitis. The aim of this study was to compare
      the efficacy of meropenem, a new carbapenem antibiotic, with that of imipenem,
      which is the standard prophylactic treatment in patients with severe acute
      pancreatitis. METHODS: One hundred seventy-six patients with necrotizing
      pancreatitis were prospectively randomized to prophylactic treatment with 0.5 g
      meropenem t.i.d. intravenously or 0.5 g imipenem q.i.d. intravenously. The
      occurrence of infection of pancreatic necrosis, rate of extrapancreatic
      infections, systemic and local complications, need for surgery, mortality rate,
      and length of hospitalization were recorded for each group. When a septic
      complication of pancreatic necrosis was suspected, fine needle aspiration with
      cultures of the sample was performed. Surgery was performed in cases of verified
      infected necrosis. CONCLUSION: No difference was observed between patients
      treated with meropenem and those treated with imipenem in terms of incidence of
      pancreatic infection (11.4% versus 13.6%) and extrapancreatic infections (21.6%
      versus 23.9%) and clinical outcome. Meropenem is as effective as imipenem in
      preventing septic complications of patients with severe acute pancreatitis.

PMID- 14576502
TI  - Activation of somatostatin receptor subtype 2 inhibits insulin secretion in the
      isolated perfused human pancreas.
AB  - OBJECTIVES: Five distinct somatostatin receptors (SSTRs) have been cloned,
      characterized, and designated SSTRs 1-5. The role of these receptors in B-cell
      signaling has not been well characterized. METHODS: In the current study, the
      isolated perfused human pancreas model was used to determine the specific effect
      of 4 different somatostatin receptor agonists on insulin secretion. CONCLUSION:
      We demonstrated that the SSTR 2 agonist and octreotide significantly suppressed
      insulin secretion. Furthermore, even during the immunoneutralization of
      endogenous intrapancreatic somatostatin, the SSTR 2 agonist was able to reverse
      the effect of somatostatin immunoneutralization by suppressing insulin secretion.
      These results demonstrate that activation of SSTR 2 suppresses insulin secretion
      in the isolated perfused human pancreas.

PMID- 14576503
TI  - Circulating ethanol does not stimulate pancreatic secretion in conscious rats.
AB  - The purpose of this study was to test the hypothesis that circulating ethanol at
      concentrations of approximately 0.1 mg% stimulates pancreatic secretion. Awake
      rats recovered from surgery were used in these experiments. Intravenous infusion
      protocols were established that produced blood ethanol concentrations 0.1 mg% for
      over an hour. Maintenance of 0.1 mg% blood ethanol concentration or transient
      concentrations as high as 0.17 mg% did not cause significant increases in
      pancreatic protein or fluid secretion. To test whether elevated blood ethanol
      would augment stimulated pancreatic secretion, the trypsin inhibitor camostat was
      infused intraduodenally at doses of 0.05, 0.2, and 0.5 mg/hr, each dose level
      infused for 2 hours. Elevated blood ethanol concentrations (0.1 mg%) did not
      significantly affect camostat-stimulated pancreatic protein or fluid secretion.
      In contrast to intravenous infusion, intraduodenal infusion of ethanol
      significantly stimulated pancreatic protein and fluid secretion, which was
      associated with blood ethanol concentrations of > or =0.19 mg%. The increases in
      pancreatic secretion were completely blocked by intravenous infusion of the
      cholecystokinin (CCK) receptor antagonist CR1409. We conclude that circulating
      ethanol does not stimulate pancreatic secretion in awake, recovered rats and that
      intraduodenal ethanol-stimulated pancreatic secretion is mediated by CCK.

PMID- 14576504
TI  - Study of the interaction of lubeluzole with cardiac sodium channels.
AB  - The effects of lubeluzole on sodium currents were examined in guinea-pig isolated
      cardiac myocytes by use of the whole-cell patch clamp technique. Lubeluzole (0.01
      100 microM) reduced peak Na+ current (INa) obtained at a holding potential of -80
      mV with an IC50 value of 9.5 (3.5-21.9) microM and a Hill coefficient of 1.1.
      These effects were rapid and reversible. Lubeluzole (10 microM) produced a shift
      in the inactivation curve to hyperpolarized potentials (by -9.7 mV, P < 0.05),
      but produced no change in the voltage-dependence of activation. Lubeluzole (10
      microM) produced significant tonic block of INa obtained at a holding potential
      of -120 mV (2.7 +/- 1.4% and 27.5 +/- 5.8% for control and lubeluzole,
      respectively; n = 6; P < 0.05). Use-dependent block of INa was also observed.
      Recovery from block was delayed by lubeluzole (10 microM; tau1=4.4 +/- 6.2,
      tau2=22.7 +/- 1.5 milliseconds for control and tau1=311 +/- 144, tau2 = 672 +/-
      23 milliseconds for lubeluzole; n = 6; P < 0.001) confirming use-dependency of
      block. The results indicate that lubeluzole produces both tonic and use-dependent
      block of cardiac sodium channels at concentrations similar to those that block
      neuronal sodium channels, due mainly to interaction of the drug with channels in
      the inactivated state.

PMID- 14576505
TI  - Anti-oxidant effects of coenzyme Q10 on experimental viral myocarditis in mice.
AB  - We studied the effects of coenzyme Q10 (CoQ10) on mice with acute myocarditis
      inoculated with the encephalomyocarditis (EMC) virus with the analysis of indices
      of effects of oxidative injury and DNA damage in the myocardium. The mice were
      treated as follows: CoQ10 group (n = 118); CoQ10 1.0 mg (0.1 mL) x 2/d (0.1
      mg/g/d), control group (n = 128); sham-liquid 0.1 mL x 2/d. The mice were
      injected intraperitoneally 1 day before and daily for 12 days after EMC virus
      inoculation. The expression of thioredoxin, a marker of oxidative stress
      overload, as well as 8-hydroxy-2'-deoxyguanosine, an established marker of DNA
      damage, in the myocardium was investigated. The survival rate was significantly
      higher (P < 0.01) in the CoQ10 group (46.8%, 29/62) than in the control group
      (14.3%, 10/70). There were significant increases of CoQ9 and CoQ10 in the heart,
      which are the biologically active forms of CoQ in mice, and significant decrease
      of serum creatine kinase (CK)-MB in the CoQ10 group as compared with the control
      group. Histologic examination showed that the severity of myocarditis was less
      severe (P < 0.01) in the CoQ10 group than in the control group. In addition, the
      up-regulation of myocardial thioredoxin with DNA damage, which was induced by the
      inflammatory stimuli by the virus, was suppressed by the CoQ10 treatment, which
      may reflect the anti-oxidant effects of CoQ10 treatment. Thus, pretreatment with
      CoQ10 may reduce the severity of viral myocarditis in mice associated with
      decreasing oxidative stress in the condition.

PMID- 14576506
TI  - Ischemic preconditioning: triggering role of nitric oxide-derived oxidants in
      isolated hearts.
AB  - There is evidence that oxidants generated during ischemic preconditioning (IPC)
      trigger or mediate cardioprotection. We examined whether a causal relationship
      exists between oxidant formation during ischemic preconditioning and
      cardioprotection. We monitored formation of dityrosine in crystalloid-perfused
      guinea pig isolated hearts after a preconditioning protocol and after prolonged
      ischemia. Superoxide dismutase, catalase, and glutathione (SCG), or the L
      arginine analogue NGnitro L-arginine methyl ester (L-NAME) were given during
      preconditioning. Dityrosine was observed in the coronary effluent immediately
      after both stimuli, but not after bracketing with SCG or L-NAME. After prolonged
      ischemia, dityrosine was significantly lower in the IPC group than in other
      groups. IPC was evidenced by improved mechanical and metabolic function on
      reperfusion, and by reduced infarction. These effects were abrogated by either
      SCG or L-NAME. These data support the hypothesis that the formation of nitric
      oxide-derived oxidants during ischemic preconditioning is causally related to
      myocardial adaptation to reperfusion injury.

PMID- 14576507
TI  - High dietary sodium blunts affects of angiotensin-converting enzyme inhibition on
      vascular angiotensin I-to-angiotensin II conversion in rats.
AB  - High sodium intake blunts the efficacy of angiotensin (Ang)-converting enzyme
      (ACE) inhibition (ACEi), but the underlying mechanism is incompletely
      characterized. High sodium has been reported to increase vascular expression and
      vascular activity of ACE. To investigate whether high-dietary sodium-induced
      effects on vascular conversion of Ang I might be involved in the sodium-induced
      blunting of the response to ACEi, the authors studied the vasoconstrictor
      responses to Ang I and Ang II of isolated aortic rings from healthy rats on low
      dietary sodium (LS: 0.05% NaCl) and high dietary sodium (HS: 2.0% NaCl) after 3
      weeks of ACEi (lisinopril 75 mg/L) or vehicle (CON). Blood pressure was similar
      in LS and HS in CON, but HS blunted the blood pressure response to ACEi.
      Functional conversion of Ang I was assessed as the difference in dose-response
      curves to Ang I and Ang II in parallel aortic rings. Sodium intake did not affect
      the dose-response curves to Ang I and Ang II in CON. In the ACEi groups, a
      significant difference was present between the curves for Ang I and Ang II on LS
      (deltaEC50, 6.7 nM; range, 2.2-13 nM; P < 0.01) but not on HS (deltaEC50: 1.3 nM;
      range, 0.0-4.1 nM, median [interquartile range], NS). Thus, HS blunts the ACEi
      induced reduction of functional vascular Ang I conversion compared with LS.
      Whether the blunted functional vascular conversion is causally related to the
      blunted blood pressure response remains to be elucidated.

PMID- 14576508
TI  - C-reactive protein directly inhibits nitric oxide production by cytokine
      stimulated vascular smooth muscle cells.
AB  - C-reactive protein (CRP) is an important risk factor for atherosclerosis and
      coronary artery disease. The authors investigated the effects of CRP on nitric
      oxide (NO) synthesis in vascular smooth muscle cells (VSMCs). Production of
      nitrite, a stable metabolite of NO, was measured, as was the expression of
      inducible NO synthase (iNOS) messenger RNA and protein in cultured rat VSMCs.
      Incubation of cultures with interleukin (IL)-1beta (10 ng/mL) caused a
      significant increase in nitrite production. C-reactive protein significantly
      decreased the IL-1beta-induced nitrite production by VSMCs in a dose-dependent
      manner (10-100 microg/mL). Incubation with IL-1beta induced expression of iNOS
      mRNA and protein in VSMCs, whereas CRP showed a suppressive effect on their
      expression. Addition of IL-1beta activated nuclear factor-kappaB (NFkappaB) in
      VSMCs, whereas CRP did not affect IL-1beta-induced NFkappaB activation. In
      conclusion, CRP acts on VSMCs and inhibits NO synthesis, which might contribute
      to the development of atherosclerosis and vascular events.

PMID- 14576509
TI  - Does QT widening in the Langendorff-perfused rat heart represent the effect of
      repolarization delay or conduction slowing?
AB  - It has been suggested that class I antiarrhythmic drugs and ischemia can widen
      the QT interval in the Langendorff-perfused rat heart preparation as a
      consequence of slowed ventricular conduction. If this were so, it would undermine
      the clinical relevance of the preparation and its effectiveness as an
      antiarrhythmic bioassay. To test this, the authors determined whether three
      different class I drugs could prolong QT in the preparation and whether this
      effect was augmented by ischemia and elevation of the potassium (K+) content of
      the perfusion solution. Baseline drug-free QT intervals correlated inversely with
      the K+ content (3 microM vs. 5 mM). QT intervals widened during the first 3-5
      minutes of ischemia (P < 0.05), then returned gradually to baseline. Lidocaine
      (3.88 microM and 12.93 microM) had no effect on the QT interval before or during
      ischemia, whereas quinidine (7.90 microM but not 0.79 microM) and flecainide
      (1.48 microM but not 0.74 microM) caused QT widening before and during ischemia
      (P < 0.05). Elevating perfusion solution K+ content from 3 microM to 5 mM reduced
      the QT-widening effects of quinidine and flecainide (P < 0.05). Because
      lidocaine, a relatively selective sodium (Na+) channel blocker, failed to widen
      QT interval whereas quinidine and flecainide (combined Na+ and K+ channel
      blockers) did so, and because K+ elevation reduced rather than potentiated the
      drug-induced QT widening, it is unlikely that Na+ channel blockade and conduction
      slowing play any role in ischemia- or class I drug-induced QT widening in this
      model.

PMID- 14576510
TI  - Comparative effects of irbesartan versus amlodipine on left ventricular mass
      index in hypertensive patients with left ventricular hypertrophy.
AB  - The aim of this study was to comparatively assess the effects of irbesartan and
      amlodipine monotherapies on left ventricular mass index (LVMI) in patients with
      mild to moderate untreated hypertension and echocardiographically determined left
      ventricular hypertrophy (LVH). Sixty hypertensive patients (35 men, 25 women;
      mean age, 52.8 years +/- 12.6) with diastolic blood pressure (BP) > or = 100 mm
      Hg were randomized to irbesartan 150 mg once daily or amlodipine 5 mg once daily
      for a 4-week titration period. Dosage of both drugs was increased to irbesartan
      300 mg once daily or amlodipine 10 mg once daily in case of sitting diastolic BP
      still >90 mm Hg after the first 2 weeks of treatment. Dosage doubling was
      necessary in more than 50% of patients in both treatment groups. After the
      titration period, only the responders (sitting diastolic BP < or = 90 mm Hg)
      entered a 5-month maintenance period. After 3 months, echocardiographically
      estimated LVMI decreased by 23.2% in the irbesartan-treated patients and 11.4% in
      the amlodipine-treated patients, with an adjusted mean difference of 11.8% in
      favor of irbesartan (P < 0.0001). After 6 months, it decreased by 24.7% in the
      irbesartan-treated patients and 13.0% in the amlodipine-treated patients, with an
      adjusted mean difference of 11.6% in favor of irbesartan (P < 0.0001).

PMID- 14576511
TI  - The influence of calcium channel antagonists on isolated human distal radial
      arteries.
AB  - A comparison was made between the efficacies and potencies of calcium channel
      antagonists on contractions induced by 5-hydroxytryptamine, norepinephrine, or
      high-potassium buffer in isolated human distal radial arteries. Also, the impact
      of removal of extracellular calcium ions on contractions induced by 5
      hydroxytryptamine or norepinephrine was assessed. Isometric contractions were
      induced by agonists, and relaxant responses to calcium channel antagonists,
      nifedipine, diltiazem, verapamil, or mibefradil were examined. 5
      hydroxytryptamine-induced contractions when compared with norepinephrine or high
      potassium induced contractions were significantly more sensitive to inhibition by
      nifedipine (pIC50 = 7.53 +/- 0.15; 6.78 +/- 0.12; 6.6 +/- 0.22, respectively,
      mean +/- SEM). Diltiazem was more effective in producing relaxations when
      contractions were elicited with 5-hydroxytryptamine (pIC50 = 6.48 +/- 0.84) or
      norepinephrine (pIC50 = 6.20 +/- 0.21) than with high potassium (pIC50 = 5.43 +/-
      0.10). Verapamil was more effective at relaxing arteries contracted with 5
      hydroxytryptamine (pIC50 = 6.09 +/- 0.19) or norepinephrine (pIC50 = 6.00 +/-
      0.17) than with high potassium (pIC50 = 5.60 +/- 0.16). Mibefradil was not very
      effective in producing relaxations. The studies revealed that removal of
      extracellular calcium significantly attenuated contractions produced by 5
      hydroxytryptamine (-67.7 +/- 6.3%) and norepinephrine (-89 +/- 1.5%). In
      conclusion, our data indicates that nifedipine was the most effective drug in
      producing relaxations; also, contractions produced by 5-hydroxytryptamine and
      norepinephrine were found to be critically dependent on the presence of
      extracellular calcium.

PMID- 14576512
TI  - Synthetic human alpha-atrial natriuretic peptide improves the management of
      postoperative hypertension and renal dysfunction after the repair of abdominal
      aortic aneurysm.
AB  - OBJECTIVE: Delayed hypertension (HT) and renal dysfunction (RD) are observed
      after aortic operations accompanied by infra-renal aortic cross-clamping (AXC).
      Atrial natriuretic peptide (ANP) has effects on vasodilation and renal
      protection, and we examined the hypothesis that synthetic human alpha-ANP (hANP)
      improves the postoperative management for abdominal aortic aneurysm (AAA).
      METHODS: Fifty patients undergoing elective aneurysmectomy for infrarenal-AAA
      between 1998 and 2001 (M:F = 43:7, mean age 70.5 +/- 7.7 years) were randomly
      allocated to one of 2 groups; Group H (n = 24) received hANP immediately after
      operation (initial dose: 0.025 microg/kg/min), and Group C (n = 26) served as a
      control group. RESULTS: All patients in Group C required nicardipine
      hydrochloride (4.41 +/- 1.68 mg/h) for prevention of postoperative HT, whereas
      only 6 patients in Group H required the increase in hANP dose due to HT (P <
      0.0001). Maximum hANP dose was 0.035 +/- 0.019 microg/kg/min. Group H showed
      significantly smaller furosemide dosage in the initial 3 days (H vs. C; 9.2 +/-
      11.0 vs. 58.8 +/- 41.5 mg, P < 0.0001), significantly lower peak-Crn (H vs. C;
      1.16 +/- 0.53 vs. 2.58 +/- 1.42 mg/dL, P < 0.0001), and significantly lower
      plasma renin-activity (7.09 +/- 2.38 vs. 11.52 +/- 4.89 ng/mL/h, P = 0.0002) and
      aldosterone (51.6 +/- 12.7 vs. 81.2 +/- 34.2 pg/mL, P = 0.0002) on the first
      postoperative day than Group C did. CONCLUSIONS: These results imply that renin
      angiotensin system may play a role in the incidence of postoperative HT and RD,
      and suggest that hANP infusion is a simple, reliable, and effective method for
      management during the immediate period after AAA operations.

PMID- 14576513
TI  - Prolonged cardiac dysfunction after withdrawal of chronic cocaine exposure in
      rats.
AB  - Cocaine abuse causes myocardial dysfunction and induces oxidative stress.
      However, the reversibility of these effects is unknown. We evaluated myocardial
      function and oxidative stress after cocaine withdrawal, in a rat model of chronic
      cocaine exposure. Standard echocardiography and Doppler tissue imaging were
      performed after 4 weeks (W4) of cocaine administration (2 x 7.5 mg/kg/d, i.p.)
      and 4 weeks after interruption (W8). At these time points, redox state (reduced
      glutathione GSH, oxidized glutathione GSH, and GSH/GSSG) as well as activities of
      GSH peroxidase (GPX), superoxide dismutase (SOD), and catalase were determined in
      the left ventricle (LV). At W4, LV fractional shortening, posterior wall
      thickening, systolic myocardial ventricular gradient (SMVG), dP/dt(max), and
      dp/dt(min) were decreased, compared with control values while LV myocardial
      thickness was increased. At W8, even though dP/dtmax and dp/dt(min) were
      restored, myocardial function was still impaired as demonstrated by the decrease
      in posterior wall thickening, and systolic myocardial velocity gradient. At W4,
      CAT and GPX activities as well as GSH/GSSG ratio were reduced while SOD activity
      was increased. Antioxidant markers and redox ratio remained altered 4 weeks after
      the last injection. Thus, these data demonstrate the persistence of LV
      dysfunction after cocaine withdrawal, which occurs in a context of a deficit in
      antioxidant defenses.

PMID- 14576514
TI  - Differential recovery of action potential duration and HERG currents from the
      effects of two methanesulfonamide class III antiarrhythmic agents, KCB-328 and
      dofetilide.
AB  - A novel pure class III antiarrhythmic agent, 1-(2-amino-4
      methanesulfonamidophenoxy)-2-[N-(3,4-dimethoxyphen-ethyl)-N-methylamino]ethane
      hydrochloride (KCB-328) prolongs action potential duration (APD) by blocking the
      rapid component delayed rectifier K+ current (IKr). However, KCB-328 manifests
      little of the reverse frequency dependence (RFD) that is a general characteristic
      of class III antiarrhythmic agents. We have studied the onset and recovery
      kinetics of KCB-328 and dofetilide on APD in guinea-pig papillary muscle and on
      human ether-a-go-go-related gene (HERG) channel, which encodes IKr, expressed in
      Xenopus oocytes. KCB-328 (1 microM) and dofetilide (0.1 microM) progressively
      increased the duration of post-rest AP at 1-Hz stimulation, with onset time
      constants of 6.4 +/- 0.6 seconds and 20.7 +/- 1.8 seconds, respectively. With a
      100-second resting period, the effect of KCB-328 recovered by 70% with a time
      constant of 13.2 +/- 4.2 seconds, whereas that of dofetilide recovered only by
      25%. Both drugs blocked activated HERG channels in a biexponential decay fashion,
      with faster time constants for KCB-328 (3 microM) than for dofetilide (0.3
      microM). After a 300-second resting period, HERG current inhibited by KCB-328 was
      recovered more at depolarized membrane potentials than at hyperpolarized ones,
      with a time constant of 179.9 seconds during the rest at -60 mV. In contrast,
      recovery after dofetilide was negligible at all voltages tested. These results
      suggest that KCB-328 binds to IKr at a preferentially open state in a use
      dependent manner, but that KCB-328 unbinds from the resting state more readily
      than dofetilide. The less striking RFD of KCB-328 than of dofetilide might be
      related to the faster recovery from its effect on IKr.

PMID- 14576515
TI  - Effects of inhibition of alpha-CGRP receptors on cardiac and peripheral vascular
      dynamics in conscious dogs with chronic heart failure.
AB  - Whether endogenous calcitonin gene-related peptide (CGRP) plays a role in heart
      failure is unclear. Seven dogs were instrumented with left ventricular (LV)
      pressure gauges, pacers, coronary occluder and aortic, atrial, and coronary sinus
      catheters. Hemodynamic recordings and response to alpha-CGRP challenge were
      obtained for baseline in the conscious state. Rapid pacing (240 beats/min) was
      then initiated. The coronary artery was occluded for 90 minutes followed by
      reperfusion after 2 weeks of pacing. After 6 weeks of pacing, LV pressure (-11 +/
      6%), LV dP/dt (-53 +/- 5%), and mean arterial pressure (-15 +/- 4%) decreased (P
      < 0.01), while left atrial pressure (+19 +/- 3 mm Hg from 7 +/- 1 mm Hg) and
      heart rate (+53 +/- 16%) increased (P < 0.01). Infusion of the alpha-CGRP
      receptor antagonist alpha-CGRP[8-37] (30 microg/kg/min, i.v.), which blocked the
      exogenous alpha-CGRP challenge, did not affect any of these indices. Regional
      blood flow, as measured by the microsphere technique, in the nonischemic
      myocardium, as well as cerebral and renal vasculatures were unaltered during the
      infusion of alpha-CGRP[8-37]. Plasma concentrations of CGRP from both arterial
      and coronary sinus samples were unchanged after 6 weeks of pacing as compared
      with control. Thus, we conclude that endogenous alpha-CGRP does not appear to
      play a major role in the regulation of cardiac and peripheral vascular dynamics
      in the late stage of heart failure.

PMID- 14576516
TI  - Age increases expression and receptor-mediated activation of G alpha i in human
      atria.
AB  - Recently, we demonstrated that beta2AR and several other Galphas-coupled
      receptors in human atria also couple to Galphai, a G protein that inhibits
      adenylyl cyclase (AC). The present study was undertaken to determine whether age
      increases expression of Galphai in human atrium, and more specifically whether it
      results in an increase in receptor-mediated activation of Galphai. Right atrial
      appendages were obtained from 14 mature adult (40-55 years) and 14 elderly (71-79
      years) patients undergoing cardiac surgery. Immunoblotting of atrial membranes
      indicates that elderly atria have 82 +/- 18% more Galphai2 than atria from mature
      adults (P < 0.002); this increase in Galphai with age is confirmed by pertussis
      toxin-catalyzed ADP-ribosylation as well as by photoaffinity labeling with
      [32P]azidoanilido-GTP. We also find that receptor-mediated activation of Galphai
      is greater in elderly atria and that both basal and receptor-mediated AC
      activities decrease in elderly atria. These decreases in AC activity can be
      reversed by disabling Galphai with pertussis toxin, indicating that the age
      dependent increases in Galphai expression and activation have functional
      consequences. Because beta2ARs in human atria mediate contractility through cAMP
      mediated phosphorylation of phospholamban, we conclude that an age-induced
      increase in Galphai may have a role in depressing cardiac function in aged human
      atria.

PMID- 14576517
TI  - Systemic depletion of macrophages by liposomal bisphosphonates reduces neointimal
      formation following balloon-injury in the rat carotid artery.
AB  - OBJECTIVES: Macrophage depletion by liposomal clodronate inhibits neointimal
      formation after balloon-injury. The present study examined bisphosphonates (BPs)
      potency-effect relationship and the role of systemic versus local monocytes in
      vascular repair. METHODS AND RESULTS: Liposomal preparations of clodronate,
      pamidronate, alendronate, and ISA-13-1 inhibited RAW-264 macrophages growth in a
      dose-response manner. Administration to balloon-injured rats suppressed
      neointimal growth. Neointima to media ratio (N/M) at 14 days was reduced from
      1.35 +/- 0.22 (control) to 0.4 +/- 0.1 and 0.9 +/- 0.17 by liposomal alendronate
      (1.5 mg/kg, i.v.) and liposomal ISA-13-1 (15 mg/kg), respectively (n = 8-10, P <
      0.05). Suppression of neointimal formation was preserved at 30 days. Subcutaneous
      administration of liposomal BP (LBP) was also effective in suppressing neointimal
      formation, while short local intraluminal application had no effect.
      Immunostaining for ED-1 and ED-2 revealed no resident macrophages in the arterial
      wall, and reduced macrophage infiltration in LBP-treated animals. Arterial PDGF-B
      chain and PDGF-beta receptor activation were reduced in LBP-treated animals and
      up-regulation of the PDGF receptor was noted. CONCLUSIONS: Systemic transient
      inactivation of monocytes and macrophages by LBPs reduced macrophage infiltration
      and neointimal formation in the rat carotid injury model. The findings
      demonstrate a BP potency-effect relationship, and highlight the role of
      circulating monocytes in vascular injury and repair.

PMID- 14576518
TI  - Non-invasive functional and biochemical assessment of mitoxantrone cardiotoxicity
      in patients with multiple sclerosis.
AB  - As mitoxantrone is a recently approved immunosuppressant for managing multiple
      sclerosis, the number of patients treated with this effective but potentially
      cardiotoxic anthracenedione derivative will increase substantially. To detect
      subclinical mitoxantrone-induced cardiotoxicity, sensitive non-invasive
      diagnostic tools are required. Assuming that changes in myocardial high-energy
      phosphate metabolism and alterations in left ventricular (LV) diastolic
      performance might be early markers of mitoxantrone-induced cardiotoxicity we
      examined fifteen MS patients treated with mitoxantrone up to 100 mg/m2 compared
      with 15 matched control MS patients. 31P-magnetic resonance (MR) spectroscopy was
      employed to measure myocardial high-energy phosphate metabolism, MR imaging for
      morphometric evaluation of changes in LV geometry. Indices of diastolic
      performance were assessed by Doppler echocardiography. In this exploratory study,
      phosphocreatine/ATP ratios were comparable between mitoxantrone-treated and
      control patients (1.48 +/- 0.23 and 1.43 +/- 0.41). LV mass, LV end-diastolic and
      systolic volumes, wall motion score, EF and cardiac output did not differ between
      both groups. All parameters of diastolic performance (E/A-ratio, isovolumic
      relaxation time, and E-wave deceleration time) were not different and within
      normal limits.In conclusion, using advanced diagnostic methodology, including
      functional, morphometric, and biochemical measurements no cardiotoxic effect of
      mitoxantrone up to a cumulative dose range of 100 mg/m2 could be detected.

PMID- 14576519
TI  - Anti-ischemic effects of ivabradine, a selective heart rate-reducing agent, in
      exercise-induced myocardial ischemia in pigs.
AB  - The effects of ivabradine, a novel heart rate-reducing agent that inhibits the
      cardiac pacemaker current If, were compared with those of the beta-adrenergic
      blocker propranolol, in a model of exercise-induced regional myocardial ischemia
      in pigs. Five Yucatan micropigs were chronically instrumented to measure
      hemodynamics, regional myocardial contractility, and local electrograms, and a
      fixed stenosis of the left anterior descending coronary artery was induced using
      a clip. Each animal underwent three experiments on different days, each
      consisting of two treadmill exercise sessions, 4 hours apart. Ivabradine 5 mg/kg,
      propranolol 5 mg/kg, or vehicle was administered orally 3 hours before the second
      exercise session. Exercises before treatment and after vehicle produced
      reproducible hemodynamic changes and regional myocardial ischemia in the area
      perfused by the stenosed coronary artery, indicated by ST segment shift and
      regional contractile dysfunction. Ivabradine and propranolol were equipotent in
      reducing heart rate at rest and limiting tachycardia during exercise. Ivabradine,
      unlike propranolol, did not reduce left ventricular contractility at rest or
      during exercise, and did not increase atrio-ventricular conduction time. Both
      compounds reduced the exercise-induced ST segment shift in the ischemic region by
      approximately 80%, but ivabradine preserved systolic shortening to a
      significantly greater degree than propranolol (P < 0.05).

PMID- 14576520
TI  - Comparison of the effects of topical levobunolol and timolol solution on the
      human ocular surface.
AB  - PURPOSE: To compare the effects of levobunolol hydrochloride and timolol maleate
      on tear volume, precorneal tear film stability, and corneal epithelial barrier
      function in normal human eyes. SUBJECTS AND METHODS: The study population
      consisted of 14 healthy volunteers. To obtain pretreatment baseline values, we
      determined the radius of the tear meniscus (RTM) by meniscometry; the noninvasive
      breakup time (NIBUT) of the precorneal tear film with a tear specular microscope;
      and corneal fluorescein uptake with a fluorophotometer. Levobunolol hydrochloride
      (0.5%) or timolol maleate solution (0.5%) was instilled twice daily for 4 weeks
      into 1 eye; the contralateral eye was treated with the other topical drug twice
      daily for the same period. At the end of the study period, the same tests were
      performed, and the pre- and posttreatment results were compared. RESULTS: Timolol
      solution did, and levobunolol did not, significantly reduce NIBUT from the
      baseline values. RTM was significantly decreased by treatment with either timolol
      or levobunolol solution. Corneal fluorescein uptake was not significantly
      changed, although it was higher after treatment with both topical drugs.
      CONCLUSIONS: Four-week treatment with timolol solution resulted in significant
      instability of the precorneal tear film. Both timolol and levobunolol solution
      significantly decreased tear volume on the ocular surface. These results indicate
      that levobunolol solution applied twice daily has equal effects on the tear
      volume and corneal epithelial barrier function as does timolol solution applied
      twice daily and that it affects precorneal tear film stability less than timolol
      solution.

PMID- 14576521
TI  - Keratometric astigmatism after suture removal in penetrating keratoplasty: double
      running versus single running suture techniques.
AB  - BACKGROUND AND OBJECTIVE: To compare astigmatism after suture removal in a
      retrospective sequential series of patients who had penetrating keratoplasty with
      either a double running suture technique or an adjustable single running suture
      technique. During the first year postkeratoplasty, when sutures were in place,
      the latter technique had produced less astigmatism. MATERIALS AND METHODS:
      Keratometry and keratometric astigmatism were measured before and after suture
      removal. We compared these variables in 30 grafts with the double running suture
      technique to the same variables in 24 grafts with the single running suture
      technique. RESULTS: The final portion of the double running suture was removed
      408 +/- 177 (mean +/- SD) days after keratoplasty, whereas the single running
      suture was removed 611 +/- 224 days after keratoplasty (P<0.001). After suture
      removal, there was no difference between the double running and single running
      groups in either mean keratometry [46.5 +/- 1.8 diopters (D) versus 45.6 +/- 2.0
      D, P=0.09, minimum detectable difference (MDD)=1.5D] or mean astigmatism (4.6 +/-
      2.7 D versus 5.2 +/- 3.2D, P=0.72, MDD=2.3). CONCLUSION: In this consecutive
      series of corneal transplants performed by one surgeon, the results suggest no
      difference in astigmatism between the two suturing techniques after all sutures
      have been removed.

PMID- 14576522
TI  - Pterygium surgery with mitomycin C: how much sclera should be left bare?
AB  - PURPOSE: To evaluate the effect of covering the sclera with conjunctiva during
      surgical treatment of pterygium on the rate of postoperative complications,
      cosmetic outcome, and risk of recurrence. METHODS: A comparative, prospective
      clinical design was used. The study population consisted of 371 consecutive
      patients with unilateral primary advanced pterygium. All underwent bare sclera
      technique for pterygium excision. At completion of surgery, topical mitomycin C
      0.02% was applied for 5 minutes. In the first 189 patients (group A), the
      conjunctiva was sutured to the sclera 2 mm from the limbus. The next 146 patients
      (group B), the conjunctiva was sutured at the limbus, covering the whole scleral
      postexcision defect. In the last 36 patients (group C), the conjunctiva remained
      unsutured to the sclera. The patients were followed for complications, cosmetic
      outcome, and recurrence for 26 months. RESULTS: After 26 months, 12 patients in
      group A (6.35%), 10 in group B (6.85%), and 9 in group C (25%) had recurrent
      pterygium. There were no cases of acute drug toxicity or scleral melting.
      Treatable delen were noted in 2 patients in group A (1.05%), 2 (1.36%) in group
      B, and 9 (25%) in group C. The cosmetic appearance was much better in group A
      than in groups B and C. CONCLUSIONS: Leaving the whole sclera uncovered in
      pterygium surgery places patients at high risk of complications and recurrence.
      There is no difference in complications and recurrence between covering the whole
      sclera with conjunctiva and leaving 2 mm bare, although the latter yields a more
      esthetic outcome.

PMID- 14576523
TI  - Therapeutic use of Focus Night & Day contact lenses.
AB  - PURPOSE: To evaluate the safety and efficacy of Focus Night & Day extended-wear
      contact lenses when used for therapeutic purposes. METHODS: Fifty eyes of 50
      consecutive patients presenting at the Ankara University Medical Center, Cornea
      and Contact Lens Service, and requiring bandage contact lens use for ocular
      surface disorders, were enrolled. All patients were fitted with Focus Night & Day
      contact lenses and were followed in regard to patient satisfaction, contact lens
      fit and performance, and success of treatment. RESULTS: Twenty-four patients
      (48%) were male, and 26 (52%) were female. Average age at the time of
      presentation was 46.9 +/- 21.6 years (range 1.5 to 88 years). Therapeutic contact
      lens indications included Fuchs' dystrophy (2 eyes), toxic epitheliopathy (1
      eye), filamentous keratopathy (2 eyes), corneal perforation (2 eyes), corneal
      stromal melting (2 eyes), recurrent corneal erosion (4 eyes), chemical or
      traumatic epithelial defect (3 eyes), epithelial irregularity (1 eye), persistent
      epithelial defect (4 eyes), lamellar laceration (5 eyes), graft insufficiency (2
      eyes), pseudophakic bullous keratopathy (7 eyes), aphakic bullous keratopathy (4
      eyes), disciform keratitis (1 eye), postkeratectomy (4 eyes), and post-amniotic
      membrane transplantation or post-limbal autograft transplantation (6 eyes). Mean
      duration of continuous contact lens wear was 2.4 +/- 3.0 months (range 3 days to
      12 months). At the end of the follow-up period, the mean change in visual acuity
      was a gain of 1.8 +/- 2.8 logMAR units (0-9 Snellen lines). No sight-threatening
      complications related to contact lens wear were encountered. A culture-negative
      sterile corneal infiltrate developed in one patient and was treated with
      cessation of lens wear and subsequent topical antibiotic and steroids.
      CONCLUSION: Focus Night & Day contact lenses are safe and effective when used for
      therapeutic purposes. Infrequent replacement of these lenses seems to be
      especially advantageous in patients for whom frequent lens insertion and removal
      may be associated with epithelial trauma, pain, and a potential increase in
      infection risk. Infrequent replacement of these lenses also decreased the office
      time and the cost of treatment without an increase in hypoxia-related
      complications.

PMID- 14576524
TI  - Human fibrin tissue glue for corneal lamellar adhesion in rabbits: a preliminary
      study.
AB  - PURPOSE: To evaluate the use of a human fibrin tissue adhesive in the adherence
      of corneal lamellar flaps in rabbit eyes. METHODS: Corneal flaps were made using
      a microkeratome in both eyes of six New Zealand white rabbits. In the right eyes,
      the flaps were glued with fibrin tissue adhesive; in the left eyes, flaps were
      allowed to heal without adhesive (controls). All eyes were treated with
      antibiotics and steroids once daily for 10 days. Slit-lamp biomicroscopy was
      performed 1 and 10 days after surgery. The rabbits with surviving flaps were
      euthanized and the corneas obtained for histopathologic examination 10 days after
      surgery. RESULTS: Slit-lamp examinations showed no interface deposits and no
      other signs of corneal toxicity. Histologically, a few inflammatory cells were
      seen in both the experimental and control eyes, and microscopic gapping and
      tissue debris were observed in three of the six control eyes. CONCLUSIONS: Human
      fibrin tissue glue was well tolerated in these eyes, with no or minimal corneal
      toxicity. Further studies are needed to determine the tensile strength of the
      adhesive bond in the cornea.

PMID- 14576526
TI  - Culture plate temperature and delayed incubation effect on bacterial recovery.
AB  - PURPOSE: To discover if initial culturing conditions (plate temperature and time
      delay to incubation) adversely influence the recovery of organisms associated
      with bacterial keratitis. METHODS: The rate of temperature equilibration of
      culture plates taken from a refrigerator and placed in an incubator and left on
      the desk was evaluated with a digital thermometer. A standard inoculum for each
      of five organisms (S. aureus, S. pneumoniae, P. aeruginosa, E. aerogenes, K.
      oxytoca) isolated from human bacterial keratitis was spread evenly on blood agar
      plates at refrigerator (Tcold; 4 degrees C), room (Troom; 24 degrees C), and
      incubator (Twarm; 37 degrees C) temperatures. The plates were then kept at room
      temperature for 0, 1, 3, 5, and 8 hours before overnight incubation at 37 degrees
      C (S. pneumoniae under microaerophilic conditions), and the number of colony
      forming units was counted. RESULTS: Cold plates took at least 15 minutes in an
      incubator to attain room temperature, and up to an hour when left on the desk.
      Increased organism recovery was found comparing both Twarm and Troom plates (6.2
      to 24.8% and 7.0 to 14.7%, respectively, P<0.001) to Tcold plates for all
      organisms except S. pneumoniae (P=0.057). Comparing Twarm plates to Troom plates
      demonstrated an increased recovery (P<0.001) for S. aureus. Delayed incubation
      resulted in decreased recovery for S. pneumoniae (P<0.001). CONCLUSIONS: Culture
      plates should preferably be warmed at least to room temperature before
      inoculation, as well as promptly incubated to increase bacterial recovery from
      cases of septic keratitis.

PMID- 14576525
TI  - Clinical appearance and microscopic analysis of mucin balls associated with
      contact lens wear.
AB  - PURPOSE: The structure of mucin balls collected from silicone hydrogel contact
      lens wearers was examined to determine their nature. METHODS: Tears containing
      mucin balls were collected using a capillary tube. These were processed for light
      microscopic histochemistry, scanning electron microscopy, and electron
      microscopic elemental analysis. Mucin balls were also observed in vivo using
      confocal microscopy. RESULTS: Histology showed that the mucin balls were PAS
      positive, indicating that glycoproteins form a major component. Lipids and
      bacteria were not detected. Scanning electron microscopy did not show the surface
      to be smooth but revealed a variation in density across the surface. Elemental
      analysis was inconclusive. CONCLUSIONS: Mucin balls are likely to be made from
      collapsed mucin and are unlikely to have been formed as a result of pearling
      around a silicon, lipid, or bacterial kernel.

PMID- 14576527
TI  - Atypical vortex pattern of corneal deposits in granular corneal dystrophy.
AB  - PURPOSE: To report the appearance of an unusual vortex pattern of corneal
      deposits in two patients with the R555W mutation in the transforming growth
      factor beta-induced gene (TGFB1) associated with granular corneal dystrophy.
      METHODS: DNA from affected patients and unaffected relatives was isolated from
      buccal swabs, and TGFB1 mutation screening was performed. RESULTS: The proband
      and an affected daughter demonstrated rays of deposits emanating from a point in
      the inferior cornea of each eye in a "sea fan" or vortex pattern. Screening all
      17 exons of TGFB1 in the proband identified a single missense mutation (C1710T)
      in exon 12, consistent with the diagnosis of granular corneal dystrophy. The
      identical mutation was identified in the affected daughter. CONCLUSIONS: In spite
      of the strict phenotype-genotype correlation reported for the TGFB1-associated
      corneal dystrophies, atypical clinical findings may be produced by previously
      identified, conserved mutations.

PMID- 14576528
TI  - Treatment of ligneous conjunctivitis with topical plasmin and topical
      plasminogen.
AB  - PURPOSE: To describe treatment of a child with recalcitrant ligneous
      conjunctivitis secondary to a systemic plasminogen deficiency. DESIGN:
      Interventional case report. METHODS: A seven-year-old boy developed severe
      unilateral membranous conjunctivitis recalcitrant to surgical debridement and
      treatment with topical prednisone, topical cyclosporine, and oral prednisone.
      Systemic evaluation revealed a severe plasminogen deficiency. RESULTS: Treatment
      with surgical debridement and topical plasmin was ineffective and resulted in
      prompt recurrence of dense conjunctival membranes. Treatment with topical
      plasminogen resulted in dramatic improvement and complete resolution of the
      membranes. CONCLUSIONS: Ligneous conjunctivitis is secondary to a systemic
      plasminogen deficiency. Treatment with topical plasminogen resulted in prompt
      resolution of the membranes. Treatment with topical plasmin was ineffective.

PMID- 14576529
TI  - Intraoperative daunorubicin versus conjunctival autograft in primary pterygium
      surgery.

PMID- 14576530
TI  - Intraocular lens power calculation after laser in situ keratomileusis and retinal
      detachment repair.

PMID- 14576532
TI  - The right dose of succinylcholine.

PMID- 14576533
TI  - Target-controlled infusions for intravenous anesthetics: surfing USA not!

PMID- 14576534
TI  - Sepsis and hypothermia: call in the granulocytes?

PMID- 14576535
TI  - A role for cyclooxygenase-1 in neuropathic pain?

PMID- 14576536
TI  - Optimal dose of succinylcholine revisited.
AB  - BACKGROUND: The authors reappraised the conventional wisdom that the intubating
      dose of succinylcholine must be 1.0 mg/kg and attempted to define the lower range
      of succinylcholine doses that provide acceptable intubation conditions in 95% of
      patients within 60 s. METHODS: This prospective, randomized, double-blind study
      involved 200 patients. Anesthesia was induced with 2 mug/kg fentanyl and 2 mg/kg
      propofol. After loss of consciousness, patients were randomly allocated to
      receive 0.3, 0.5, or 1.0 mg/kg succinylcholine or saline (control group).
      Tracheal intubation was performed 60 s later. A blinded investigator performed
      all laryngoscopies and also graded intubating conditions. RESULTS: Intubating
      conditions were acceptable (excellent plus good grade combined) in 30%, 92%, 94%,
      and 98% of patients after 0.0, 0.3, 0.5, and 1.0 mg/kg succinylcholine,
      respectively. The incidence of acceptable intubating conditions was significantly
      greater (P < 0.05) in patients receiving succinylcholine compared with those in
      the control group but was not different among the different succinylcholine dose
      groups. The calculated doses of succinylcholine (and their 95% confidence
      intervals) that were required to achieve acceptable intubating conditions in 90%
      and 95% of patients at 60 s were 0.24 (0.19-0.31) mg/kg and 0.56 (0.43-0.73)
      mg/kg, respectively. CONCLUSIONS: The use of 1.0 mg/kg of succinylcholine may be
      excessive if the goal is to achieve acceptable intubating conditions within 60 s.
      Comparable intubating conditions were achieved after 0.3, 0.5, or 1.0 mg/kg
      succinylcholine. In a rapid-sequence induction, 95% of patients with normal
      airway anatomy anesthetized with 2 mug/kg fentanyl and 2 mg/kg propofol should
      have acceptable intubating conditions at 60 s after 0.56 mg/kg succinylcholine.
      Reducing the dose of succinylcholine should allow a more rapid return of
      spontaneous respiration and airway reflexes.

PMID- 14576537
TI  - The "intubating dose" of succinylcholine: the effect of decreasing doses on
      recovery time.
AB  - BACKGROUND: The usually cited "intubation dose" of succinylcholine is 1.0 mg/kg.
      In the majority of patients, this dose will produce apnea of sufficient duration
      that significant hemoglobin desaturation may occur before neuromuscular recovery
      takes place in those whose ventilation is not assisted. This study was undertaken
      to examine the extent to which reducing this dose would decrease the duration of
      action of succinylcholine. METHODS: During stable desflurane/oxygen/opioid
      anesthesia and after adequate twitch stabilization, neuromuscular function was
      recorded with an acceleromyographic monitor. Supramaximal stimuli were delivered
      at 0.10 Hz. Patients received 0.40, 0.60, or 1.0 mg/kg succinylcholine, and
      twitch height was monitored for at least 20 min thereafter. RESULTS: The onset
      times to maximal effect were 105 +/- 23 s, 81 +/- 19 s, and 71 +/- 22 s,
      respectively. The lowest dose (0.40 mg/kg) did not reliably produce 100% twitch
      depression. The times to 90% twitch recovery at the adductor pollicis in the
      three groups were 6.6 +/- 1.5 min, 7.6 +/- 1.6 min, and 9.3 +/- 1.2 min,
      respectively. CONCLUSIONS: Reducing the dose of succinylcholine from 1.0 mg/kg to
      0.60 mg/kg shortens the duration of effect at the adductor pollicis by more than
      90 s. The authors believe that even this modest decrease in the duration of drug
      induced paralysis is often worth pursuing.

PMID- 14576538
TI  - Influence of nitrous oxide on minimum alveolar concentration of sevoflurane for
      laryngeal mask insertion in children.
AB  - BACKGROUND: Inhalational induction with sevoflurane and nitrous oxide is
      frequently used for Laryngeal Mask Airway (LMA; Laryngeal Mask Company, Henley-on
      Thames, United Kingdom) insertion in children. The authors determined the
      influence of nitrous oxide on the minimum alveolar concentration (MAC) of
      sevoflurane for LMA insertion. METHODS: One hundred twenty unpremedicated
      children (age, 1-9 yr; American Society of Anesthesiologists physical status I)
      were randomly assigned to receive 1 of 15 end-tidal concentrations of nitrous
      oxide and sevoflurane for inhalational induction via a facemask: 0% nitrous oxide
      with 1.2, 1.4, 1.6, 1.8, or 2.0% sevoflurane; 33% nitrous oxide with 0.8, 1.0,
      1.2, 1.4, or 1.6% sevoflurane; or 67% nitrous oxide with 0.4, 0.6, 0.8, 1.0, or
      1.2% sevoflurane. The LMA was inserted after steady state end-tidal anesthetic
      concentrations had been maintained for 15 min. The response to insertion was
      recorded by three independent blinded observers. The interaction between nitrous
      oxide and sevoflurane was determined using logistic regression analysis. RESULTS:
      The MAC of sevoflurane for LMA insertion (95% confidence limit) was 1.57% (1.42
      1.72%), and the concentration of sevoflurane required to prevent movement in 95%
      of children was 1.99% (1.81-2.57%). The addition of 33% and 67% nitrous oxide
      linearly decreased the MAC of sevoflurane for LMA insertion by 22% and 49%,
      respectively (P < 0.001). The interaction coefficient between nitrous oxide and
      sevoflurane did not differ from zero (P = 0.7843), indicating that the relation
      was additive. CONCLUSIONS: Nitrous oxide and sevoflurane suppress the responses
      to LMA insertion in a linear and additive fashion in children.

PMID- 14576539
TI  - Women appear to have the same minimum alveolar concentration as men: a
      retrospective study.
AB  - BACKGROUND: A recent report finds that elderly Japanese women given xenon have a
      significantly smaller (26% less) MAC (minimum alveolar concentration required to
      eliminate movement in response to surgical incision in 50% of patients) than
      Japanese men of the same age. The authors assessed whether this finding applied
      to other/all anesthetics. METHODS: The authors reviewed data obtained previously
      for 258 patients (127 women and 131 men) anesthetized with desflurane, diethyl
      ether, halothane, methoxyflurane, sevoflurane, or xenon. Data were normalized to
      the MAC for the anesthetic as determined by logistic regression (i.e., MAC would
      equal a value of 1.000). RESULTS: The MAC for the normalized combined (all) data
      for women (1.013 +/- 0.017; mean +/- SEM) did not differ significantly from the
      normalized combined data for men (1.005 +/- 0.009), and neither differed
      significantly from 1.000. However, a significantly smaller MAC value was found
      for women in two studies of sevoflurane (subsets of the above studies) given to
      Japanese patients: 12% in one study and 16% in the other. CONCLUSIONS: Overall,
      no difference in MAC was found for women versus men. Whether women (particularly
      older Japanese women) have a smaller MAC than men remains to be confirmed by
      prospective studies.

PMID- 14576540
TI  - Women have the same desflurane minimum alveolar concentration as men: a
      prospective study.
AB  - BACKGROUND: Women generally report greater sensitivity to pain than do men, and
      healthy young women require 20% more anesthetic than healthy age-matched men to
      prevent movement in response to noxious electrical stimulation. In contrast,
      minimum alveolar concentration (MAC) for xenon is 26% less in elderly Japanese
      women than in elderly Japanese men. Whether anesthetic requirement is similar in
      men and women thus remains in dispute. The authors therefore tested the
      hypothesis that the desflurane concentration required to prevent movement in
      response to skin incision (MAC) differs between men and women. METHODS: Using the
      Dixon "up and down" method, the authors determined MAC for desflurane in 15
      female and 15 male patients (18-40 yr old) undergoing surgery. RESULTS: MAC was
      6.2 +/- 0.4% desflurane for women versus 6.0 +/- 0.3% for men (P = 0.31), a
      difference of only 3%. These data provide 90% power to detect a 9% difference
      between the groups. CONCLUSIONS: The MAC of desflurane did not differ between
      young men and women undergoing surgery with a true surgical incision. Although
      pain sensitivity may differ in women versus men, MAC of desflurane does not.

PMID- 14576541
TI  - Comparison of the LMA-classic with the new disposable soft seal laryngeal mask in
      spontaneously breathing adult patients.
AB  - BACKGROUND: The laryngeal mask airway LMA-Classic has been used widely in
      clinical practice. A new disposable supraglottic airway device, the Soft Seal LM,
      has been introduced recently. In a randomized study, the authors compared the LMA
      Classic and the disposable Soft Seal LM in terms of their clinical performance,
      cuff pressures during nitrous oxide anesthesia, position of the laryngeal mask in
      situ by fiberoptic evaluation, and morbidity in a wide range of routine general
      surgery procedures. METHODS: A total of 200 adult patients were randomly assigned
      to a size 4 laryngeal mask in two equal-sized groups for airway management during
      surgery: (1) LMA-Classic (Intavent Orthofix Ltd., Maidenhead, Berkshire, United
      Kingdom); or (2) Soft Seal LM (Portex Ltd., Hythe, Kent, United Kingdom).
      Anesthesia was administered with fentanyl, propofol, nitrous oxide, oxygen, and
      sevoflurane. The variables studied were ease of insertion, fiberoptic view, time
      in situ, incidence of blood on the laryngeal mask at the time of removal, and the
      incidence of postoperative sore throat at 2 and 24 h. The laryngeal mask cuff
      pressures were measured continuously. Intracuff pressure limitation was not
      attempted. RESULTS: The LMA-Classic and the Soft Seal LM showed similar clinical
      performances, as shown by their insertion time (successful insertion at first
      attempt was achieved within 20 s in 97% with LMA-Classic trade mark vs. 95% with
      Soft Seal LM), fiberoptic evaluation of the anatomic position of the laryngeal
      mask, and satisfactory anesthesia conditions. Laryngeal mask cuff pressures
      increased from 45 to 100.3 mmHg in the LMA-Classic and from 45 to 46.8 mmHg in
      the Soft Seal LM (P < 0.001). Macroscopic blood was seen on only four occasions
      in the LMA-Classic group. The incidence of sore throat was significantly
      increased at 2 h postoperatively when using the LMA-Classic, although there was
      no difference at 24 h after surgery. CONCLUSIONS: In spontaneously breathing
      adult patients requiring a size 4 laryngeal mask airway, the new disposable Soft
      Seal LM device is an acceptable alternative to the reusable LMA-Classic trade
      mark, resulting in a good laryngeal seal and offering similar clinical
      performance. Cuff pressures increase substantially when the LMA-Classic is used
      but not when using the Soft Seal LM. There was less trauma to patients using the
      Soft Seal LM, as assessed by the incidence of sore throat in the early
      postoperative period.

PMID- 14576542
TI  - Narcotrend and Bispectral Index monitor are superior to classic
      electroencephalographic parameters for the assessment of anesthetic states during
      propofol-remifentanil anesthesia.
AB  - BACKGROUND: A new electroencephalogram monitor, the Narcotrend, was developed to
      measure anesthetic depth. The authors compared the Narcotrend, the Bispectral
      Index, and classic electroencephalographic and hemodynamic parameters during
      anesthesia with propofol and remifentanil. METHODS: The authors investigated 25
      patients undergoing laminectomy at different anesthetic states: awake, steady
      state anesthesia, first reaction during emergence, and extubation. Narcotrend
      value; BIS; relative power (percent) in delta, theta, alpha, and beta; median
      frequency; spectral edge frequency; and hemodynamic parameters were recorded
      simultaneously. The ability of the classic and processed electroencephalographic
      and hemodynamic parameters to predict the clinically relevant anesthetic states
      of awake, steady state anesthesia, first reaction, and extubation was tested
      using prediction probability. RESULTS: Only the Narcotrend was able to
      differentiate between awake versus steady state anesthesia and steady state
      anesthesia versus first reaction/extubation with a prediction probability value
      of more than 0.90. CONCLUSIONS: Modern electroencephalographic parameters,
      especially Narcotrend, are more reliable indicators for the clinical assessment
      of anesthetic states than classic parameters.

PMID- 14576543
TI  - Using front-end kinetics to optimize target-controlled drug infusions.
AB  - BACKGROUND: The mode of drug administration, blood sampling schedule, and
      sampling site affect the pharmacokinetic model derived. The present study tested
      the hypothesis that three-compartment pharmacokinetic model parameters derived
      from arterial drug concentrations obtained after rapid intravenous administration
      can be used to design a target-controlled drug infusion (TCI) that deviates
      minimally from the target. METHODS: Arterial thiopental concentration data
      obtained from the moment of injection in a previous study of five dogs were used.
      Three three-compartment models were constructed, one based on early
      concentrations classically obtained at 1, 2, and 3 min; another using all
      concentrations obtained beginning with the thiopental recirculation peak; and the
      last with the initial distribution volume (VC) fixed to the sum of VC and the
      nondistributive volume of the recirculatory model from the earlier study. Using
      these models, TCIs were designed that would maintain 20 mug/ml thiopental
      concentrations in VC for 60 min if simulated with the models used in their
      design. Drug concentrations resulting from these TCIs were then simulated using
      recirculatory model kinetics, and prediction errors were evaluated. RESULTS:
      Models with VCs estimated from intermittent or frequent early blood
      concentrations overestimated not only VC but also the volume and clearance of the
      rapidly equilibrating tissues, and their TCIs significantly overshot the target.
      With VC fixed to recirculatory model parameters, drug distribution was described
      in a manner consistent with that of the recirculatory model, and the TCI deviated
      minimally from the target. A similar three-compartment model was derived from
      data obtained from a simulation of a 2-min infusion using recirculatory kinetic
      parameters. CONCLUSIONS: Because three-compartment models based on drug
      concentration histories obtained after rapid intravenous administration do not
      characterize VC accurately, TCIs based on them produce concentrations exceeding
      the target. A model capable of producing TCIs deviating minimally from the target
      can be derived from data obtained during and after a brief drug infusion.

PMID- 14576544
TI  - Deleterious effects of mild hypothermia in septic rats are ameliorated by
      granulocyte colony-stimulating factor.
AB  - BACKGROUND: The authors studied the effects of mild hypothermia on the outcome in
      a rat model of intraabdominal sepsis and tested whether granulocyte colony
      stimulating factor (G-CSF) augments the host response and improves outcome during
      mild hypothermia. METHODS: A rat model of peritoneal contamination and infection
      with human stool bacteria was used to simulate clinical trials that included
      increasing complexity. In trial 1, postoperative hypothermia (32 degrees C) was
      compared with normothermia (38 degrees C), without supportive treatment (10 rats
      per group). In trial 2, with a more severe infection, rats were given antibiotic
      prophylaxis. Using 20 rats per group, the authors compared postoperative
      hypothermia (32 degrees C), normothermia, and postoperative hypothermia (32
      degrees C) with 20 mug/kg G-CSF prophylaxis given 12 h before surgery and 12 h
      and 36 h after surgery. The primary endpoint was death at 120 h. Secondary
      endpoints were systemic cytokine concentrations, leukocyte counts, and the
      phagocytic activity of granulocytes and monocytes. RESULTS: In trial 1, 50% of
      the normothermia group and 10% of the postoperative hypothermia group survived.
      In trial 2, 50% of the normothermia group, 20% of the hypothermia group, and 60%
      of the hypothermia plus G-CSF group survived. Postoperative hypothermia plus G
      CSF reduced plasma concentrations of interleukin-6 (hypothermia group, 511 +/-
      104 pg/ml; hypothermia plus G-CSF group, 247 +/- 51 pg/ml) and macrophage
      inflammatory protein-2 (hypothermia group, 239 +/- 43 pg/ml; hypothermia plus G
      CSF group, 178 +/- 21 pg/ml). CONCLUSIONS: In this rat model of intraabdominal
      sepsis, postoperative hypothermia was deleterious. However, G-CSF treatment,
      initiated before contamination, reduced the mortality rate, increased the
      neutrophil count, and downgraded the systemic cytokine response.

PMID- 14576545
TI  - Lidocaine enhances Galphai protein function.
AB  - BACKGROUND: Local anesthetics inhibit several G protein-coupled receptors by
      interaction with the Galphaq protein subunit. It is not known whether this effect
      on G protein function can be extrapolated to other classes of G proteins. The
      authors investigated interactions of lidocaine with the human adenosine 1
      receptor (hA1R)-coupled signaling pathway. Activated A1Rs couple to adenylate
      cyclase via the pertussis toxin sensitive Galphai protein, thereby decreasing
      cyclic adenosine monophosphate formation. A1Rs are widely expressed and abundant
      in the spinal cord, brain, and heart. Interactions of LAs with the hA1R-coupled
      transduction cascade therefore might produce a broad range of clinically relevant
      effects. METHODS: The function of hA1Rs stably expressed in Chinese hamster ovary
      cells was determined with assays of cyclic adenosine monophosphate, receptor
      binding, and guanosine diphosphate/guanosine triphosphate gamma35S exchange by
      using reconstituted defined G protein subunits. Involvement of phosphodiesterase
      and Galphai was characterized by using the phosphodiesterase inhibitor rolipram
      and pertussis toxin, respectively. RESULTS: Lidocaine (10-9-10-1 M) had no
      significant effects on agonist or antagonist binding to the hA1R or on receptor-G
      protein interactions. However, cyclic adenosine monophosphate levels were reduced
      significantly to 50% by the LAs, even in the absence of an A1R agonist or
      presence of an A1R antagonist. This effect was unaffected by rolipram (10 mum),
      but abolished completely by pretreatment with pertussis toxin, which inactivates
      the Galphai protein. Therefore, the main target site for LAs in this pathway is
      located upstream from adenylate cyclase. CONCLUSIONS: Lidocaine potentiates
      Galphai-coupled A1R signaling by reducing cyclic adenosine monophosphate
      production. The study suggests an interaction site for LAs in a Galphai-coupled
      signaling pathway, with the Galphai protein representing the prime candidate.
      Taken together with previous results showing inhibitory LA interactions on the
      Galphaq protein subunit, the data in the current study support the hypothesis
      that specific G protein subunits represent alternative sites of LA action.

PMID- 14576546
TI  - Open-lung protective ventilation with pressure control ventilation, high
      frequency oscillation, and intratracheal pulmonary ventilation results in similar
      gas exchange, hemodynamics, and lung mechanics.
AB  - BACKGROUND: Pressure control ventilation (PCV), high-frequency oscillation (HFO),
      and intratracheal pulmonary ventilation (ITPV) may all be used to provide lung
      protective ventilation in acute respiratory distress syndrome, but the specific
      approach that is optimal remains controversial. METHODS: Saline lavage was used
      to produce acute respiratory distress syndrome in 21 sheep randomly assigned to
      receive PCV, HFO, or ITPV as follows: positive end-expiratory pressure (PCV and
      ITPV) and mean airway pressure (HFO) were set in a pressure-decreasing manner
      after lung recruitment that achieved a ratio of Pao2/Fio2 > 400 mmHg. Respiratory
      rates were 30 breaths/min, 120 breaths/min, and 8 Hz, respectively, for PCV,
      ITPV, and HFO. Eucapnia was targeted with peak carinal pressure of no more than
      35 cm H2O. Animals were then ventilated for 4 h. RESULTS: There were no
      differences among groups in gas exchange, lung mechanics, or hemodynamics. Tidal
      volume (PCV, 8.9 +/- 2.1 ml/kg; ITPV, 2.7 +/- 0.8 ml/kg; HFO, approximately 2.0
      ml/kg) and peak carinal pressure (PCV, 30.6 +/- 2.6 cm H2O; ITPV, 22.3 +/- 4.8 cm
      H2O; HFO, approximately 24.3 cm H2O) were higher in PCV. Pilot histologic data
      showed greater interstitial hemorrhage and alveolar septal expansion in PCV than
      in HFO or ITPV. CONCLUSION: These data indicate that HFO, ITPV, and PCV when
      applied with an open-lung protective ventilatory strategy results in the same gas
      exchange, lung mechanics, and hemodynamic response, but pilot data indicate that
      lung injury may be greater with PCV.

PMID- 14576547
TI  - Evaluation of rapid ischemic preconditioning in a rabbit model of spinal cord
      ischemia.
AB  - BACKGROUND: Rapid ischemic preconditioning (IPC) has been shown to reduce
      cellular injury after subsequent cardiac and cerebral ischemia. However, the data
      on rapid IPC of the spinal cord is limited. The authors investigated whether
      pretreatment with sublethal ischemia of spinal cord can attenuate neuronal injury
      after spinal cord ischemia in rabbits. METHODS: Forty-seven male New Zealand
      white rabbits were randomly assigned to one of three groups (n = 15 or 16 each).
      In the IPC(-) group, the infrarenal aorta was occluded for 17 min to produce
      spinal cord ischemia. In the IPC(+) group, 5 min of aortic occlusion was
      performed 30 min before 17 min of spinal cord ischemia. In the sham group, the
      aorta was not occluded. Hind limb motor function was assessed at 3 h, 24 h, 4
      days, and 7 days after reperfusion using Tarlov scoring (0 = paraplegia; 4 =
      normal). Animals were killed for histopathologic evaluation at 24 h or 7 days
      after reperfusion. The number of normal neurons in the anterior spinal cord (L4
      L6) was counted. RESULTS: Neurologic scores were significantly higher in the
      IPC(+) group than the IPC(-) group at 3 and 24 h after reperfusion (P < 0.05).
      However, neurologic scores in the IPC(+) group gradually decreased and became
      similar to those in the IPC(-) group at 4 and 7 days after reperfusion. At 24 h
      after reperfusion, the numbers of normal neurons were significantly higher in the
      IPC (+) group than in the IPC(-) group (P < 0.05) and were similar between the
      IPC(+) and sham groups. At 7 days after reperfusion, there was no difference in
      the number of normal neurons between the IPC(+) and IPC(-) groups. CONCLUSION:
      The results indicate that rapid IPC protects the spinal cord against neuronal
      damage 24 h but not 7 days after reperfusion in a rabbit model of spinal cord
      ischemia, suggesting that the efficacy of rapid IPC may be transient.

PMID- 14576548
TI  - Selective blockade of AT1 receptor attenuates impairment of hypotensive
      autoregulation and improves cerebral blood flow after brain injury in the newborn
      pig.
AB  - BACKGROUND: Fluid percussion injury (FPI) in piglets produces vasoconstriction of
      pial arteries (PAs), decreases in cerebral blood flow (CBF), and impairment of
      hypotensive autoregulation. Two types of angiotensin II receptors, AT1 and AT2,
      have been identified in the brain. This study characterized the effect of
      pretreatment with AT1- and AT2-selective antagonists on CBF and hypotensive
      autoregulation after FPI. METHODS: Fluid percussion injury was induced in
      chloralose-anesthetized newborn pigs equipped with closed cranial windows. CBF
      was determined by the radiolabeled microsphere technique. RESULTS: Moderate and
      severe hypotension (71 +/- 3, 53 +/- 2, and 40 +/- 1 mmHg for normotension,
      moderate hypotension, and severe hypotension, respectively) elicited PA dilation
      without changes in CBF in sham control piglets. The AT1 antagonist ZD 7155
      partially restored impaired hypotension-induced PA dilation after FPI (19 +/- 1
      and 34 +/- 1 vs. 5 +/- 1 and 7 +/- 1 vs. 12 +/- 1 and 20 +/- 3% for PA dilation
      during moderate and severe hypotension in sham control, FPI, and FPI + ZD 7155
      animals, respectively). ZD 7155 also blunted the reductions in CBF during
      normotension and hypotension observed in untreated animals (43 +/- 4, 38 +/- 5,
      and 55 +/- 3 vs. 32 +/- 4, 19 +/- 2, and 27 +/- 5% CBF reductions during
      normotension, moderate hypotension, and severe hypotension in untreated and
      pretreated animals, respectively). The AT2 selective antagonist PD 123,319 did
      not restore hypotension-induced PA dilation and did not prevent decreases in CBF
      observed during normotension and moderate and severe hypotension after FPI.
      CONCLUSION: These data indicate that blockade of the AT1 and not the AT2 receptor
      diminished the reduction in hypotensive PA dilation after FPI. AT1 blockade also
      blunted the decrease in CBF during normotension as well as the further decrease
      in CBF observed during hypotension after FPI. These data suggest that AT1
      receptor activation by angiotensin II contributes to cerebrovascular
      dysregulation during hypotension after FPI.

PMID- 14576549
TI  - Cholinergic reversal of isoflurane anesthesia in rats as measured by cross
      approximate entropy of the electroencephalogram.
AB  - BACKGROUND: Pharmacologic modulation of the state of consciousness is of interest
      for clinical practice and for a better understanding of anesthetic mechanisms.
      The cholinergic activating system is an important regulator of the state of
      consciousness during general anesthesia. Entropy of the electroencephalogram has
      been proposed as a promising measure of anesthetic depth. The authors have shown
      that volatile anesthetics decrease cross-approximate entropy (C-ApEn) of the
      bihemispheric frontal electroencephalogram in rats. The effect of cholinergic
      agents on C-ApEn has not been examined. Here, the authors test the hypothesis
      that cholinergic activation reverses the effect of isoflurane anesthesia on C
      ApEn. METHODS: An electroencephalogram in the 1- to 100-Hz range was recorded
      bipolarly, with epidural leads from the frontal cortex of both hemispheres, and
      used to calculate C-ApEn, which reflects statistical independence of
      bihemispheric electroencephalographic activity. Cholinesterase inhibitor,
      neostigmine (25 mug), or the muscarinic agonist oxotremorine (25 mug) were
      infused intracerebroventricularly while the rats were inhaling 1.0% (0.7 minimum
      alveolar concentration) isoflurane. In other animals, isoflurane was lowered to
      0.4% (0.3 minimum alveolar concentration) to assess the electroencephalogram in a
      sedated, waking state. RESULTS: At 1.0% isoflurane, C-ApEn decreased by 54%
      compared with that at 0.4%, but the motor reflex response to tail pinch was still
      present. Cholinergic agents reversed the electroencephalogram-depressant effect
      of isoflurane, i.e., C-ApEn rose to the level measured at 0.4% isoflurane. The
      rise in C-ApEn was paralleled by the appearance of spontaneous limb and orofacial
      explorative movements, suggesting a return of consciousness. In contrast,
      cholinergic agents fully blocked the motor reflex to tail pinch. CONCLUSIONS: C
      ApEn of the bihemispheric electroencephalogram correlates with the return of
      spontaneous motor signs but not with the nociceptive reflex. Cerebral cholinergic
      activation dissociates central and peripheral anesthetic effects. C-ApEn, a novel
      measure of interhemispheric electroencephalogram independence, is a promising
      correlate of depth of sedation and state of consciousness.

PMID- 14576550
TI  - Induction of malignant hyperthermia in susceptible swine by 3,4
      methylenedioxymethamphetamine ("ecstasy").
AB  - BACKGROUND: 3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") can mediate acute
      toxic effects such as muscle rigidity, metabolic acidosis, and hyperthermia.
      Because of close clinical similarities, an association between MDMA intoxication
      and malignant hyperthermia (MH) was suggested. The aim of this study was to
      investigate whether MDMA is a trigger of MH in susceptible swine. METHODS: MH
      nontriggering general anesthesia was performed in six MH-susceptible (MHS) and
      six MH-normal swine. The animals were exposed to MDMA in cumulative doses of 0.5,
      1, 2, 4, 8, and 12 mg/kg. The clinical occurrence of MH was defined by
      achievement of two of three conditions: central venous Pco2 >/=75 mmHg, central
      venous pH </= 7.20, and increase of body core temperature >/= 2.0 degrees C. Once
      MH occurred, a standardized therapy with dantrolene, sodium bicarbonate, and
      hyperventilation with 100% oxygen was initialized. RESULTS: Administration of 8
      mg/kg MDMA triggered MH in all MHS swine. The MH-normal swine also developed
      clinical signs of hypermetabolism, but even after administration of 12 mg/kg
      MDMA, changes were moderate compared with the MHS swine. Dantrolene therapy of
      MDMA-induced MH crisis in the MHS swine partially counteracted the clinical signs
      of MH immediately. CONCLUSIONS: MDMA induces MH in genetically susceptible swine
      in relevant doses. Therefore, MHS patients should avoid use of MDMA or related
      drugs. Patients with a personal or family history of MDMA-induced hyperthermia
      should be tested for a diagnosis of MH susceptibility. Dantrolene is effective in
      therapy of MDMA-induced porcine MH.

PMID- 14576551
TI  - Effects of spontaneous breathing during airway pressure release ventilation on
      intestinal blood flow in experimental lung injury.
AB  - BACKGROUND: In critical illness, the gut is susceptible to hypoperfusion and
      hypoxia. Positive-pressure ventilation can affect systemic hemodynamics and
      regional blood flow distribution, with potentially deleterious effects on the
      intestinal circulation. The authors hypothesized that spontaneous breathing (SB)
      with airway pressure release ventilation (APRV) provides better systemic and
      intestinal blood flow than APRV without SB. METHODS: Twelve pigs with oleic acid
      induced lung injury received APRV with and without SB. When SB was abolished,
      either the tidal volume or the ventilator rate was increased to maintain pH and
      arterial carbon dioxide tension constant as compared to APRV with SB. Systemic
      hemodynamics were determined by double indicator dilution. Blood flow to the
      intestinal mucosa-submucosa and muscularis-serosa was measured using colored
      microspheres. RESULTS: Systemic blood flow increased during APRV with SB. During
      APRV with SB, mucosal-submucosal blood flow (ml. g-1. min-1) was 0.39 +/- 0.21 in
      the stomach, 0.76 +/- 0.35 in the duodenum, 0.71 +/- 0.35 in the jejunum, 0.71 +/
      0.59 in the ileum, and 0.63 +/- 0.21 in the colon. During APRV without SB and
      high tidal volumes, it decreased to 0.19 +/- 0.03 in the stomach, 0.42 +/- 0.21
      in the duodenum, 0.37 +/- 0.10 in the jejunum, 0.3 +/- 0.14 in the ileum, and
      0.41 +/- 0.14 in the colon (P < 0.001, respectively). During APRV without SB and
      low tidal volumes, the respective mucosal-submucosal blood flows decreased to
      0.24 +/- 0.10 (P < 0.01), 0.54 +/- 0.21 (P < 0.05), 0.48 +/- 0.17 (P < 0.01),
      0.43 +/- 0.21 (P < 0.01), and 0.50 +/- 0.17 (P < 0.001) as compared to APRV with
      SB. Muscularis-serosal perfusion decreased during full ventilatory support with
      high tidal volumes in comparison with APRV with SB. CONCLUSION: Maintaining SB
      during APRV was associated with better systemic and intestinal blood flows.
      Improvements were more pronounced in the mucosal-submucosal layer.

PMID- 14576552
TI  - Severe hypotension is not essential for isoflurane neuroprotection against
      forebrain ischemia in mice.
AB  - BACKGROUND: Volatile anesthetics provide protection in experimental models of
      global cerebral ischemia. To date, all models evaluated have included profound
      systemic arterial hypotension as a component of the ischemic insult. This study
      was designed to determine if isoflurane protection persists in a global insult
      devoid of hypotension. METHODS: C57BL/6J mice having a high incidence of
      posterior communicating artery atresia were anesthetized with isoflurane (1.2%)
      or fentanyl/N2O and subjected to bilateral carotid artery occlusion for 15 min or
      20 min with normotension (80-110 mmHg mean arterial pressure) or for 10 min with
      hypotension (35 mmHg mean arterial pressure). Three days later, neurologic
      function and histologic damage were assessed. Other mice underwent measurement of
      intraischemic cerebral blood flow (4-iodo-N-methyl-[14C]antipyrine
      autoradiography) or plasma norepinephrine. RESULTS: Isoflurane reduced the
      percentage of hippocampal CA1 dead neurons (e.g., 10 min bilateral carotid
      occlusion + hypotension: 43 +/- 18 (isoflurane) vs. 67 +/- 20 (fentanyl/N2O), P =
      0.003; 20 min bilateral carotid occlusion + normotension: 49 +/- 27 (isoflurane)
      vs. 71 +/- 22 (fentanyl/N2O), P = 0.003). Isoflurane also reduced CA3 damage and
      improved neurologic function under all conditions. Intraischemic forebrain blood
      flow was similar during bilateral carotid occlusion plus normotension for the two
      anesthetic states. Plasma norepinephrine values were greater when hypotension was
      added to the ischemic insult. CONCLUSIONS: Isoflurane resulted in improved
      neurologic function and reduced histologic damage regardless of the presence or
      absence of systemic hypotension during the ischemic insult. This indicates that
      beneficial effects of isoflurane are most likely attributable to direct effects
      at the neuronal level as opposed to indirect effects resulting from interactions
      with profound hypotension.

PMID- 14576553
TI  - Arthroscopic knee surgery does not modify hyperalgesic responses to heat injury.
AB  - BACKGROUND: Experimental studies suggest that surgical injury may up- or down
      regulate nociceptive function. Therefore, the aim of this clinical study was to
      evaluate the effect of elective arthroscopically assisted knee surgery on
      nociceptive responses to a heat injury. METHODS: Seventeen patients scheduled to
      undergo repair of the anterior cruciate ligament and 16 healthy controls were
      studied. The first burn injury was induced 6 days before surgery, and the second
      burn was induced 1 day after surgery with a contact thermode (12.5 cm2, 47
      degrees C for 7 min) placed on the medial aspect of the calf contralateral to the
      surgical side. Ibuprofen and acetaminophen were given for 2 days before the first
      burn injury and again from the time of surgery. In the controls, the two burn
      injuries were separated by 7 days. Sensory variables included cumulated pain
      score during induction of the burn (visual analog scale), secondary hyperalgesia
      area, and mechanical and thermal pain perception and pain thresholds assessed
      before and 1 h after the burn injury. RESULTS: The heat injuries induced
      significant increases in pain perception (P < 0.001) and decreases in pain
      thresholds (P < 0.02). Baseline heat pain thresholds were higher during the
      second burn injury in patients (P < 0.001) and controls (P < 0.01). However,
      there were no significant differences in pain to heat injury (P > 0.8), secondary
      hyperalgesia areas (P > 0.1), mechanical and thermal pain perception (P > 0.1),
      or mechanical and thermal pain thresholds (P > 0.08) in the burn area before
      surgery compared to after surgery. CONCLUSION: Arthroscopic knee surgery did not
      modify nociceptive responses to a contralaterally applied experimental burn
      injury.

PMID- 14576554
TI  - Quality of recovery from anesthesia in neurosurgical patients.
AB  - BACKGROUND: Factors influencing quality of recovery in cranial and spinal
      neurosurgical patients are not known, possibly because of lack of a suitable
      instrument. Therefore, the authors measured quality of recovery using the QoR-40
      score (a 40-item questionnaire on quality of recovery from anesthesia). METHODS:
      With informed consent, 200 patients undergoing elective neurosurgery were
      recruited. The QoR-40 score, visual analog scores for pain and quality of
      recovery, and data on complications were collected over 90 days. The
      psychometrics of the QoR-40 were tested and regression models were developed to
      determine predictors of quality of recovery and postoperative pain. RESULTS: The
      QoR-40 score demonstrated significant responsiveness, validity, and reliability.
      In cranial surgery patients, QoR-40 scores were lower on days 1 and 2 than either
      preoperatively or on days 3, 30, and 90. In spinal surgery patients, QoR-40
      scores were lower preoperatively and on days 1 and 2 than on days 3, 30, and 90.
      Longer duration of surgery, more complications, and higher visual analog scores
      for pain were predictors of poor quality of recovery on day 3. Cranial surgery
      patients had moderately severe pain on days 1 and 2, whereas spinal surgery
      patients reported moderate pain for the whole study period. Neurologic deficits
      were negatively correlated with QoR-40 scores in cranial and spinal surgery
      patients. CONCLUSIONS: The QoR-40 score is a useful instrument with which to
      assess quality of recovery in cranial and spinal surgery patients. Postoperative
      pain and neurologic deficits correlate with poor quality of recovery in these
      patients.

PMID- 14576555
TI  - Efficacy, safety, and pharmacokinetics of levobupivacaine with and without
      fentanyl after continuous epidural infusion in children: a multicenter trial.
AB  - BACKGROUND: Levobupivacaine, the levo-enantiomer of bupivacaine, is as potent as
      bupivacaine but less toxic. Therefore, the authors investigated the efficacy,
      safety, and pharmacokinetics of perioperative epidural levobupivacaine with and
      without fentanyl in children. METHODS: After Research Ethics Board approval and
      informed written consent, 120 healthy children aged 6 months to 12 yr who were
      scheduled to undergo urologic or abdominal surgery were randomized in a double
      blinded and concealed manner to receive one of four epidural solutions as a
      continuous infusion for 24 h: 0.125% levobupivacaine; 0.0625% levobupivacaine; 1
      mug/ml fentanyl; or the combination, 0.0625 levobupivacaine and 1 mug/ml
      fentanyl. After induction of anesthesia and tracheal intubation, a lumbar
      epidural catheter was sited, a loading dose was administered (0.75 ml/kg
      levobupivacaine, 0.175%), and the epidural infusion was commenced. The primary
      endpoint was the need for rescue analgesia (morphine) in the first 10 h after
      surgery. Pain, motor strength, and side effects were recorded for 24 h. Venous
      blood was collected from 18 children to determine the plasma concentrations of
      levobupivacaine and/or fentanyl before and 2, 4, 8, 16, 24, and 26 or 30 h after
      the start of the epidural infusion. RESULTS: Of the 114 children who were
      analyzed for intention to treat, a similar number of children in each group
      reached the 10-h mark. The time to the first dose of morphine in the first 10 h
      was less in the plain fentanyl group (P < 0.044). All other effects were similar
      among the four groups. The plasma concentration of levobupivacaine increased
      during the infusion period, reaching a maximum of 0.76 +/- 0.11 mug/ml in the
      0.125% group and 0.48 +/- 0.12 mug/ml in the 0.0625% group by 24 h. The plasma
      concentration of fentanyl also increased steadily, reaching a maximum
      concentration of 0.37 +/- 0.11 ng/ml by 24 h. CONCLUSION: We conclude that
      0.0625% levobupivacaine without fentanyl is an effective perioperative epidural
      solution in children when infused at a rate of 0.3 ml. kg-1. h-1. The plasma
      concentrations of 0.125% and 0.0625% levobupivacaine and fentanyl (1 mug/ml) at
      the end of a 24-h infusion are low.

PMID- 14576556
TI  - Cyclooxygenase-1 in the spinal cord is altered after peripheral nerve injury.
AB  - BACKGROUND: The mechanisms underlying neuropathic pain are incompletely
      understood and its treatment is often unsatisfactory. Spinal cyclooxygenase-2
      (COX-2) expression is upregulated after peripheral inflammation, associated with
      spinal prostaglandin production leading to central sensitization, but the role of
      COX isoenzymes in sensitization after nerve injury is less well characterized.
      The current study was undertaken to determine whether COX-1 was altered in this
      model. METHODS: Male rats underwent partial sciatic nerve transsection (PSNT) or
      L5-L6 spinal nerve ligation (SNL). Four weeks after PSNT and 4 h, 4 days, or 2
      weeks after SNL, COX-1 immunohistochemistry was performed on the L2-S2 spinal
      cord. RESULTS: COX-1 immunoreactivity (COX-1-IR) was unaffected 4 h after SNL. In
      contrast, 4 days after SNL, the number of COX-1-IR cells increased in the
      ipsilateral spinal cord. COX-1-IR increased in cells with glial morphology in the
      superficial laminae, but decreased in the rest of the ipsilateral spinal cord 4
      weeks after PSNT and 2 weeks after SNL. These changes in immunostaining were
      greatest at the L5 level. CONCLUSION: These data suggest that COX-1 expression in
      the spinal cord is not static, but changes in a time- and laminar-dependent
      manner after nerve injury. These anatomic data are consistent with observations
      by others that spinally administered specific COX-1 inhibitors may be useful to
      prevent and treat neuropathic pain.

PMID- 14576557
TI  - Inhibition of spinal prostaglandin synthesis early after L5/L6 nerve ligation
      prevents the development of prostaglandin-dependent and prostaglandin-independent
      allodynia in the rat.
AB  - BACKGROUND: Prostaglandins, synthesized in the spinal cord in response to noxious
      stimuli, are known to facilitate nociceptive transmission, raising questions
      about their role in neuropathic pain. The current study tested the hypothesis
      that spinal nerve ligation-induced allodynia is composed of an early
      prostaglandin-dependent phase, the disruption of which prevents allodynia.
      METHODS: Male Sprague-Dawley rats, fitted with intrathecal drug delivery or
      microdialysis catheters, underwent left L5-L6 spinal nerve ligation or sham
      surgery. Paw withdrawal threshold, brush-evoked behavior, and the concentration
      of prostaglandin E2 (PGE2) in spinal cerebrospinal fluid ([PGE2]dialysate) were
      determined for up to 24 days. PGE2-evoked glutamate release from spinal slices
      was also determined. RESULTS: Paw withdrawal threshold decreased from at least 15
      g (control) to less than 4 g, beginning 1 day after ligation. Brushing the
      affected hind paw evoked nociceptive-like behavior and increased [PGE2]dialysate
      (up to 257 +/- 62% of baseline). There was no detectable change in basal
      [PGE2]dialysate from preligation values. The EC50 of PGE2-evoked glutamate
      release (2.4 x 10-11 M, control) was significantly decreased in affected spinal
      segments of allodynic rats (8.9 x 10-15 M). Treatment with intrathecal S(+)
      ibuprofen or SC-560, beginning 2 h after ligation, prevented the decrease in paw
      withdrawal threshold, the brush-evoked increase in [PGE2]dialysate, and the
      change in EC50 of PGE2-evoked glutamate release. R(-)-ibuprofen or SC-236 had no
      effect. CONCLUSIONS: The results of this study provide solid evidence that spinal
      prostaglandins, synthesized by cyclooxygenase-1 in the first 4-8 h after
      ligation, are critical in the pathogenesis of prostaglandin-dependent and
      prostaglandin-independent allodynia and that their early pharmacologic disruption
      affords protection against this neuropathic state in the rat.

PMID- 14576558
TI  - The critical role of concentration for lidocaine block of peripheral nerve in
      vivo: studies of function and drug uptake in the rat.
AB  - BACKGROUND: The adjustment of local anesthetic dosage for peripheral nerve block
      must meet two basic requirements: a drug concentration sufficient to inhibit Na+
      channels to the point of impulse failure and a volume of drug sufficient to
      expose a length of nerve longer than the "critical length" for propagation
      failure. This study examines the lidocaine dosage requirement, in milligrams, for
      functionally assayed sciatic nerve block in the rat using a fourfold range of
      volume corresponding to concentrations from 2 to 7 mg/ml and compares these
      blocks with the intraneural lidocaine content after injection of equipotent
      doses. METHODS: Lidocaine was injected percutaneously at the sciatic nerve in
      volumes of 0.05 ml, 0.1 ml, and 0.2 ml (all at pH 6.8), and quantitative
      neurobehavioral assays were conducted on male Sprague-Dawley rats weighing from
      200 to 250 g. The dose requirements for 50% maximum possible effect (ED50) and
      for just achieving complete block (i.e., minimal blocking dose for 90% effect),
      the fraction of completely blocked animals, and the duration of complete block at
      all doses were assessed for the inhibition of three different functions:
      proprioception, motor, and nocifensive activities. Radiolabeled (14C) lidocaine
      was injected in separate experiments, and the total drug content and its
      longitudinal distribution were determined in nerves dissected from animals
      (sevoflurane anesthetized) at 10 min, the time of peak block, after injection of
      the E50 and minimal blocking dose for 100% effect for the three different
      volumes. RESULTS: For all functions, the smaller the volume, the lower was the
      E50, resulting in a nearly constant concentration to achieve an equivalent degree
      of block. Durations of block were longer, and the dose to full block was lower
      for the smaller injected volumes. Intraneural lidocaine, at the equipotent doses
      for analgesia, was not related to concentration but rather increased with
      increasing volume, being almost proportional to the given dose. The longitudinal
      spread of lidocaine was also greater with increasing volume of lidocaine
      solution. CONCLUSION: Blocks of greater depth and longer duration result from
      injection of smaller volumes and, correspondingly, higher lidocaine
      concentrations containing the same dose. The corollary is that lower lidocaine
      doses are required to achieve the same effect when smaller volumes are injected.
      Curiously, when the equivalent E50 is injected, total drug taken into the nerve
      is less from the smaller volumes than from the larger volumes, even though the
      peak functional effects are equal. Total intraneural local anesthetic may not
      represent the effective drug in the compartment that contains nerve axons, the
      actual location of neural blockade.

PMID- 14576559
TI  - Cyclooxygenase-2 inhibitors in postoperative pain management: current evidence
      and future directions.

PMID- 14576560
TI  - Reporting of ethical approval and informed consent in clinical research published
      in leading anesthesia journals.
AB  - BACKGROUND: Ethical conduct in human research in anesthesia includes approval by
      an institutional review board (IRB) or ethics committee and informed consent.
      Evidence of these is sometimes lacking in journal publications. METHODS: The
      authors reviewed all publications involving human subjects in six leading
      anesthesia journals for the year 2001 (n = 1189). Rates of IRB approval and
      informed consent were examined and compared with potential predictors that
      included journal, type of publication, and patient demographics (age, sex,
      elective or emergency status). Rates were compared by use of chi-square and
      logistic regression. RESULTS: The authors found that IRB approval was documented
      in 71% of publications and consent was obtained in 66% of publications.
      Significant variation in IRB approval and consent was found among journals (P <
      0.0005) and according to type of publication (P < 0.0005). Because publication
      type affected rates of IRB approval and consent (trials > mechanistic studies >
      observational studies > case reports), an analysis restricted to prospective
      studies also found a significant difference in IRB approval and consent among
      journals (P < 0.0005). CONCLUSIONS: This study suggests that rates of IRB
      approval and informed consent vary among publications in anesthesia journals.
      Clearer guidelines (and author adherence) for all types of publication are
      needed, both as a protection for research subjects and to maintain public trust
      in the process.

PMID- 14576561
TI  - Target-controlled drug delivery: progress toward an intravenous "vaporizer" and
      automated anesthetic administration.

PMID- 14576562
TI  - Biotransformation of halothane in humans. 1967.

PMID- 14576563
TI  - Bispectral index decreased to "0" in propofol anesthesia after a cross-clamping
      of descending thoracic aorta.

PMID- 14576564
TI  - Recording electrocardiograms can be dangerous.

PMID- 14576565
TI  - Successful resuscitation from prolonged ventricular fibrillation using a portable
      percutaneous cardiopulmonary support system.

PMID- 14576566
TI  - Neuropathy following axillary brachial plexus block: is it the tourniquet?

PMID- 14576567
TI  - Investigation of electrochemical carbon monoxide sensor monitoring of anesthetic
      gas mixtures.

PMID- 14576568
TI  - Is the Parker Flex-Tip tube really superior to the standard tube for fiberoptic
      orotracheal intubation?

PMID- 14576569
TI  - Fiberoptic intubation: troubles with the "Tube"?

PMID- 14576570
TI  - Posterior approach to the sciatic nerve: can "common sense" replace science and
      logic?

PMID- 14576571
TI  - Acute myocardial infarction: which treatment?

PMID- 14576572
TI  - Preoperative cardiology consultation: how helpful is it?

PMID- 14576573
TI  - Indications for cardiology consultation.

PMID- 14576574
TI  - Isoflurane promotes extravascular fluid accumulation in humans.

PMID- 14576575
TI  - Low volume neurolytic celiac plexus block with computed tomography guidance.

PMID- 14576576
TI  - A device to stimulate central venous cannulation in the human patient simulator.

PMID- 14576577
TI  - The rapid infusion system: error of the infused volume readout caused by the
      kinking of a tube.

PMID- 14576578
TI  - [Should one screen systematically for genetic haemochromatosis?].

PMID- 14576579
TI  - [The consequences of the heat wave in August 2003 on the mortality of the
      elderly. The first overview].
AB  - THE DELETERIOUS EFFECTS OF HEAT WAVES: In fragile persons, particularly in the
      elderly, heat waves provoke excessive mortality. They may also have indirect
      effects through the decompensation of a chronic, notably cardiovascular or
      respiratory, disease, or direct heat stroke effects. Heat stroke is defined as a
      severe disease with body temperature exceeding 40 degrees C and central
      neurological manifestations, heat stroke in the very elderly leads to a high rate
      of mortality, particularly when complications related to bed rest and loss of
      autonomy are since added. Regarding therapeuty, treatment of heat stroke relies
      on cooling the body and reanimation measures to compensate organ failure, with
      relief of the dehydration hypovolemia. The heat wave in August 2003 provoked
      excess mortality particularly in the elderly with 69% of the deaths concerning
      persons aged over 75. In the future, preventive measures must be taken to limit
      the health consequences of any heat waves to come.

PMID- 14576580
TI  - [Pseudoxanthoma elasticum, 5 case reports].
AB  - INTRODUCTION: Pseudoxanthoma elasticum (PXE) is an inherited metabolic disease
      with many systemic manifestations. We report 5 cases. OBSERVATIONS: The first
      patient presented cutaneous (yellowish grouped papules with reticulate
      pigmentation) and ocular manifestations (angioid streaks). The second patient is
      the sister of the first and presented the same clinical signs. The third is the
      mother of the two previous patients. The diagnosis of PXE was made on using a
      skin biopsy of healthy skin during family screening. The fourth patient presented
      yellow grouped papules with cutaneous hyper-elasticity and angioid streaks. The
      fifth patient presented essentially cardiovascular symptoms: arterial
      hypertension, total aortal dilation, arteriopathy and a cerebral vascular
      accident. DISCUSSION: Cutaneous manifestations are frequent (70 to 85%). Ocular
      signs are associated with the cutaneous signs in around 90% of PXE. The vascular
      lesions condition the vital prognosis. The gold standard of diagnosis is skin
      biopsy taken from damaged skin but it can also be positive even in normal skin
      (cases 3 and 5). Our series is characterised by the existence of unusual clinic
      manifestations of PXE: reticulated pigmentation and total aortal dilation.
      CONCLUSION: The PXE is a rare metabolic disease whose diagnosis is classically
      histopathological. Nowadays, molecular diagnosis is also possible.

PMID- 14576581
TI  - [Assessment of the habits of physicians involved in the management of HIV
      infected patients. A clinical audit on the biological follow-up].
AB  - BACKGROUND: The aim of this study was to assess the habits of hospital and
      community-based physicians involved in the management of HIV-infected patients
      and to measure the gap between their practice and follow-up guidelines. METHOD:
      The guidelines considered as reference were the 1998 Dormont report. Data were
      prospectively collected from the medical files of the first 10 HIV-infected
      patients who presented for an out-patient visit (laboratory tests at initial
      consultation, type and frequency of follow-up during the previous year, relation
      between biological data and treatment strategy). RESULTS: 22 physicians (14
      hospital-based physicians (HP) and 8 community-based general practitioners (GP)
      participated in the survey. Initial biological data were available for 211
      patients; 45% had tests strictly conforming to the recommendations (HP: 57%, GP
      23%; p<0.001). Among patients followed by a GP, the initial biological assessment
      was adequate in 7% of cases when an opiate substitute was prescribed versus 33%
      in the absence of opiate substitute prescription (p=0.05). For all patients,
      syphilis serology was the test most frequently lacking (38%). Among 78 patients
      with HIV-RNA levels>5,000 copies/ml, 18% did not benefit from a change in
      treatment. Among the patients treated by a GP, 15% had a three-fold increase in
      HIV-RNA, compared to their initial measurement. Of these, 3/4 were redirected to
      a hospital out-patient unit. CONCLUSION: This study highlights the discrepancy
      between initial laboratory testing and expert recommendations, particularly
      concerning patients attended by a GP. Improvement in data collection is
      essential. However, recommendations concerning patients' biological follow-up are
      applied, with the exception of the delay between the initial prescription or
      treatment modification and HIV-RNA measurement, which should be shortened.

PMID- 14576582
TI  - [Severe Legionnaire's disease revealing an invasive aspergillosis in an
      apparently immunocompetent patient].
AB  - INTRODUCTION: Invasive aspergillosis, a sever disease, usually occurs in immuno
      depressed patients. However, it may also develop in presumably immuno-competent
      patients. OBSERVATION: A 54-year-old man, smoker, was hospitalised for hypoxemia
      of the right lung and septic shock, rapidly requiring mechanical ventilation
      combined with administration of vasopressors, and followed by dialysis because of
      the rapid worsening of an acute kidney failure. The diagnosis of pulmonary
      Legionnaire's disease was made on the second day in view of the positivity of the
      urinary legionella antigen. The progression of the disease was marked by the
      discovery of a histologically documented gastric aspergillosis and three
      abscessed intracerebral lesions within the context of a strongly positive
      aspergillus antigenemia. The disease worsened and the patient died on D 17,
      despite the antibiotic and anti-aspergillus treatments, haemodynamic support and
      dialysis. DISCUSSION: To our knowledge, the association of invasive aspergillosis
      and severe Legionnaire's disease has never been described in an presumably
      immunocompetent patient. This clinical case suggests the existence, other than
      the usual risk factors of invasive aspergillosis that characterise profound
      states of immunodepression, of more subtle alterations in the immune system that
      may enhance this type of infection.

PMID- 14576584
TI  - [Non-traumatic VI paralysis might evoke mumps].

PMID- 14576583
TI  - [Acute severe leukoencephalitis with posterior lesions due to Borrelia
      burgdorferi infection].
AB  - INTRODUCTION: Central nervous system manifestations represent 0.54 to 8% of
      neurological complication in Lyme disease. OBSERVATION: A 78-year-old woman
      presented a severe meningo-encephalitis with visual disorders (agnosia, alexia)
      progressing towards coma. Cranial magnetic resonance imaging revealed large areas
      of hypersignal T2 in the white matter of the lower, parieto-occipital lobes and
      left temporal lobe. The cerebrospinal fluid (CSF) contained 16 then 293 white
      corpuscles/mm3 of lympho-monocytes, increased protein level from 2.67 to 5.83 g/l
      and an increase in IgG index with oligoclonal distribution of IgG. Serological
      Elisa analysis for Lyme disease was slightly positive in blood (confirmed by
      western blot) but clearly in the CSF (IgG and IgM). Treatment with ceftriaxone
      followed by methylprednisolone provided clinical improvement 3 months later.
      DISCUSSION: Acute meningo-encephalitis is often benign, protein-like and of good
      prognosis: the gnosic visual disorders with posterior leukoencephalopathy are
      unusual. A blood level of specific antibodies slightly positive on Elisa at the
      early stage of the infection warrants confirmation by Western blot in the blood
      and by Elisa in the CSF. Additional corticosteroid therapy may be required in the
      severe forms that evoke acute disseminated encephalomyelitis.

PMID- 14576585
TI  - [Viral genomic screening before transfusion. The first French case of HIV-1
      infection discovered in pre-serological phase].

PMID- 14576586
TI  - [Munchhausen's syndrome with an artificial psychiatric disorder].

PMID- 14576588
TI  - [Q fever, a potential biowarfare agent].
AB  - SEVERAL POSSIBLE METHODS OF TRANSFUSION: Q fever is a zoonosis due to Coxiella
      burnetii. Its interest as a potential biowarfare agent is in its possible
      transmission by inhalation of sprayed particles. This form of transmission would
      probably be used: the inhalation of 1 to 10 bacteria could provoke the
      development of an infection in humans. Another possible method of transmission in
      the context of a terrorist act would be the intentional introduction of the
      bacteria into foodstuff. A DISABLING WEAPON: However, C. burnetii has never been
      used as a biological weapon. The probability that this germ could be used is very
      low: indeed, the incubation of Q fever is very long, and the majority of the
      infections is asymptomatic and mortality is low. In fact C. burnetii would more
      likely be used as a disabling weapon.

PMID- 14576587
TI  - [Antipsychotic drugs. Risk factors for diabetes].
AB  - ANTIPSYCHOTICS AND DIABETES: After 50 years' use of antipsychotics, it is
      pertinent to draw-up a circumspect review of the side effects of these
      psychotropic agents. Moreover, few articles have attempted to elucidate the
      relationship between the monitoring of carbohydrate metabolism and the
      prescription of this type of medication. SEVERAL MECHANISMS AT THE ORIGIN OF AN
      IMBALANCE IN GLYCAEMIA: Antipsychotics, notably the atypical forms, represent an
      additional factor of risk for developing diabetes. The weight gain secondary to
      this treatment plays an important part in this imbalance, but other mechanisms
      may also contribute. DEPENDING ON THE TYPE OF ANTIPSYCHOTIC: Our present
      knowledge is insufficient to be able to quantify the effect of each atypical
      antipsychotic on diabetes. The only tendency that has been reproduced in several
      studies concerns the increased risk associated with dibenzodiazepine
      antipsychotics (clozapine and olanzapine), compared with the other
      antipsychotics.

PMID- 14576589
TI  - [Invalidity in the general health scheme].
AB  - THE CONTEXT OF ATTRIBUTION: The invalidity insurance is aimed at providing
      financial assistance to working people aged under 60 years of age and who have
      lost more than 2/3 of their capacity to work or earn a living, following a non
      occupational disease or accident or due to "premature ageing of the organism".
      THREE CATEGORIES OF INVALIDITY: Depending on the extent of the reduction in
      earning capacity, distinction is made between invalid persons capable of earning
      a living, those totally incapable of working and persons incapable of working but
      who also are obliged to rely on help of a third person to perform ordinary daily
      functions. THE ATTRIBUTION CRITERIA: The evaluation is made by the counselling
      physician of the social security system, who must take into account not only the
      medical but also professional and social criteria. The invalidity can be revised.
      Since the pension is attributed temporarily, it can be suspended or withdrawn.
      ASSISTANCE IN THE CASE OF REFUSAL: There are 3 routes of assistance, depending on
      whether the refusal is administrative, medical due to a non-stabilised affection,
      or medical due to a stabilised affection with incapacity inferior to 2/3.

PMID- 14576590
TI  - [What is the future for laparoscopic colorectal surgery?].

PMID- 14576591
TI  - [Information for the patient. 1/2 the contribution of the law dated March 4,
      2202].

PMID- 14576592
TI  - [EVE, a regional campaign for the screening of cervical cancer. Organization, 7
      years results and perspectives].
AB  - OBJECTIVE: Based on the 7-years results, assess the interest of organised
      cervical cancer screening on regional level (the EVE campaign). ORGANISATION AND
      METHOD: The screening relied on existing medical structures. The centralised data
      collection, with data from the cyto-pathology laboratories assessed the quality
      of screening and the participation of the women to the follow-up of abnormal
      smears. The campaign run by a local women's rights association and sponsored by
      National educational and health information funds (FNPEIS) and the local
      councils. RESULTS: To date, 814 649 smears in the Bas-Rhin and 62 227 in the Haut
      Rhin have been collected. After 3 years, 72% of women aged 25 to 64 in the year
      1997, in the Bas-Rhin, had had at least one smear, and 82% after 5 years.
      Inadequate smears represented less than 1% of all smears of the region.
      Pathological smears represented around 4% of the total and benefited from strict
      monitoring which could be improved. However this could be improved on since only
      75% of women in whom a low-grade lesion was suspected underwent a second
      examination within the year that followed. The rate was on 80% for those with
      suspected high-grade lesions. Reminders made by the EVE association, in agreement
      with practitioners, permitted postponed follow-up and improved screening
      coverage. CONCLUSION: The EVE programme clearly shows that organized screening is
      feasible in France because the results obtained are satisfactory in terms of
      screening coverage and quality of smears. Centralised data collection permits
      detection of possible weak points and contributes to the improvement in efficacy.

PMID- 14576593
TI  - [Identification of drug misuse. Study of spontaneous notifications of adverse
      drug events in a regional safety reporting centre].
AB  - INTRODUCTION: The misuse of drugs, common practice for some, is a source of
      iatrogenic diseases and considerable supplementary costs in hospital budgets. The
      aim of this study was to quantify the number of adverse events (AE) related to
      the misuse of drugs. METHODS: This was a study conducted on 200 new validated AE
      case reports. In each report, we searched for the drug(s) responsible and checked
      whether the prescription respected the SPC (summary of product characteristics)
      and current guidelines or not. RESULTS: Among the 200 reports, 49 (24.5%) cases
      of AE were related to the misuse of a drug in 46 patients, with a mean age of
      65.8 years [24 to 97]. Among these cases, 33 (67.3%) were at the origin of
      hospitalisation or prolongation of the latter. In 17 cases (34.7%), there was no
      therapeutic alternative to the drug used in the framework of misuse. DISCUSSION:
      The notion of good or bad use of a drug progresses with the life of the drug. We
      therefore selected as criterion of misuse the non-respect of the SCP but also
      other guidelines. Regarding the cases that could have been avoided, these
      concerned an AE related to poor surveillance and assessment of the benefit/risk
      ratio of treatments prescribed to elderly patients and also the commonplace use
      of non-steroidal anti-inflammatories, at the origin of digestive haemorrhages.
      CONCLUSION: The prevention of misuse implies all the actors of the health system.
      A reassessment of the prescription of certain therapeutic classes of drugs would
      avoid a great number of iatrogenic accidents and would lead to considerable
      economy in the field of health.

PMID- 14576594
TI  - [Hypersensitive reaction to abacavir or syphilitic hepatitis?].
AB  - INTRODUCTION: Syphilis remains a current infection in France, with an increase in
      cases associated with the increase in sexual practices at risk. OBSERVATION: An
      HIV-seropositive homosexual male presented with a perturbed hepatic profile and
      roseola-like exanthema 15 days after starting treatment with Trizivir. Because of
      the combination of hepatitis and cutaneous eruption evoking hypersensitivity to
      abacavir, treatment was suspended, but no improvement was noted. The diagnosis of
      syphilitic hepatitis associated with roseola was made following a sero-conversion
      and improvement was obtained with benzathine-penicillin and the re-introduction
      of Trizivir without further problem. COMMENTS: This case report underlines the
      possibility of discovering syphilis when confronted with cholestatic and
      cytolytic hepatitis that regresses with penicillin and is isolated or associated
      with evocative cutaneous signs.

PMID- 14576595
TI  - [Prevention of preeclampsia].
AB  - THE CURRENT SITUATION: Preeclampsia is associated with increased risk of adverse
      maternal (abruptio placentae, HELLP syndrome, eclampsia.) and perinatal death.
      Its prevention, therefore, is of particular importance. The latter must be
      determined together with the group of women who would benefit from it. THE
      INTEREST OF ASPIRIN: The best studied preventive treatment is low dose aspirin.
      The various studies on low-dose aspirin have confirmed its safety in pregnant
      women. These studies, in small cohorts of selected patients at risk or in large
      series of women with moderate risk, show that the use of aspirin is associated
      with a 15% reduction in the risk of preeclampsia. OTHER THAN ASPIRIN: Other
      preventive treatments, such as calcium have not demonstrated their efficacy, or
      their effect requires confirmation, such as with anti-oxidants or low molecular
      weight heparin. IN PRACTICE: The prevention of preeclampsia currently relies on
      low-dose aspirin started at the beginning of pregnancy. The moderate benefit of
      such prevention justifies its administration in patients at high risk, selected
      on their obstetrical past history.

PMID- 14576596
TI  - [Diabetes and schizophrenia, which links?].
AB  - WHAT IS OBSERVED: Epidemiology and clinical practice show an increased prevalence
      of diabetes in schizophrenic patients, preceding even the use of antipsychotics.
      Several patho-physiological mechanisms have been proposed to explain the
      phenomenon, although none is completely satisfactory. SEVERE CONSEQUENCES:
      Diabetic schizophrenics exhibit a significantly greater number of other physical
      diseases than non-diabetic schizophrenic patients. These diseases are at the
      origin of early mortality and reduced quality of life. THE NEED FOR SCREENING:
      Schizophrenic patients should be included in the groups of those at risk for
      diabetes, together with patients treated with anti-psychotics. Diabetes is
      diagnosed if fasting blood sugar is>7.0 mmol/L and a glucose tolerance test>11,1
      mmol/L. IN PRACTICE: The epidemiology and extent of the impact on mortality and
      morbidity of the association between schizophrenia and diabetes mellitus requires
      particular attention of the practitioners and the screening for diabetes, its
      prevention and treatment must be conducted according to regularly updated
      guidelines.

PMID- 14576597
TI  - [The sick building syndrome (SBS)].
AB  - AN INCREASINGLY COMMON ENVIRONMENTAL HEALTH PROBLEM: Complaints related to indoor
      environment represent one of the most frequent problems that environmental health
      practitioners are confronted with. Hence the incidence of the Sick Building
      Syndrome (SBS) has been increasing since the Seventies. DIFFERING DEFINITIONS AND
      CLINICAL PRESENTATIONS: The WHO defines SBS as an excess of complaints and
      symptoms occurring in certain occupants of non-industrial buildings. The syndrome
      can only be evoked after elimination in the person concerned of a disease related
      to the building, the aetiological agent of which is identifiable. The symptoms
      described during SBS (headaches, concentration problems, asthenia, irritation of
      the skin or nasal mucosa, of the eyes and upper respiratory tract.) are non
      specific and frequently observed in the general population. AN UNKNOWN CASE, BUT
      NUMEROUS AETIOLOGICAL FACTORS SUSPECTED: There is no unanimously accepted
      definition nor physio-pathological theory to explain the occurrence of SBS in a
      particular building. Many favouring factors, including the type and rate of
      ventilation, volatile organic compounds, particles and humidity have been
      suspected. TECHNICAL, SOCIAL, AND MEDICAL MANAGEMENT IS REQUIRED: Although the
      symptoms are benign, they can be uncomfortable or even handicapping and prevent
      the functioning of workplaces. The SBS, the social and economical costs of which
      are high, requires multidisciplinary management.

PMID- 14576598
TI  - [Antibiotics: occasional individual benefits but always collective risks!].

PMID- 14576599
TI  - [Imiquimod and resiquimod. The onset of a new pharmaco-therapeutic class?].

PMID- 14576600
TI  - [The history of Tunisian pemphigus].

PMID- 14576601
TI  - [Community-acquired cutaneous infections: causal role of some bacteria and
      sensitivity to antibiotics].
AB  - OBJECTIVE: Identify the bacteria responsible for cutaneous infections observed in
      private practice and test their sensitivity to currently used antibiotics.
      PATIENTS AND METHODS: The patients were examined by dermatologists. A
      bacteriological sample was taken and sent to a central laboratory for
      identification of the germ and antibiograms were performed and the minimal
      inhibiting concentrations (MIC) determined. RESULTS: Folliculitis, impetigo and
      furuncles were the three most frequent primary infections. Four hundred and forty
      three patients were included and 442 samples were placed in culture. Cultures
      were positive in 265 cases (a single bacterial strain in 231 cases).
      Staphylococcus aureus was isolated in 208 cases, streptococci in 11 and
      enterobacteria in 3; occasionally several germs were present. Eight strains of
      staphylococci were meti-R (4 p. 100). All the strains were sensitive to
      pristinamycin and mupirocin and 90 p. 100 were sensitive to fusidic acid.
      CONCLUSION: The occurrence and diffusion of resistant strains is a daily concern
      in hospitals. In general practice, although care must be taken, the problem
      rarely occurs and the antibiotics used remain effective.

PMID- 14576602
TI  - [A model-based comparison of cost effectiveness of imiquimod versus
      podophyllotoxin for the treatment of external anogenital warts in France].
AB  - OBJECTIVES: For the National health scheme, to compare the costs and the efficacy
      of treatment of external anogenital warts with imiquimod and podophyllotoxin and
      laser therapy in the case of failure or relapse. PATIENTS AND METHODS: A model
      simulating the two successive treatments was built. In the first phase, the two
      topical treatments applied by the patients: podophyllotoxin for 4 weeks and
      imiquimod for 16 weeks were compared. In the case of failure or relapse, laser
      therapy that is widely used in France in this indication and, was applied. The
      efficacy of the topical treatments was assessed after reanalysis of the results
      of two controlled clinical trials versus placebo. These two trials were retained
      because they were comparable in method and had been recently published at the
      same time. A review of the literature assessed the results of laser therapy. A
      survey was conducted to collect the medical resources consumed by the different
      treatments. RESULTS: Imiquimod provided a clearance rate of 49.5 p. 100, i.e.,
      the disappearance of the lesions at 16 weeks, greater than that of
      podophyllotoxin (28.3 p. 100) at 4 weeks. The relapse rate was lowest with
      imiquimod (13.3 p. 100) than with podophyllotoxin (30.9 p. 100). The remission
      rate without relapse 3 months after the end of treatment was, including the
      laser, of 62 p. 100 following imiquimod and of 47 p. 100 following
      podophyllotoxin. The costs per patient cured was of 668 Euros for imiquimod and
      of 689 Euros for podophyllotoxin. CONCLUSION: Imiquimod, because of its greater
      initial efficacy, is at least as cost-effective as podophyllotoxin the treatment
      of external genital warts.

PMID- 14576603
TI  - [The value of radiological follow-up for stage III melanoma].
AB  - INTRODUCTION: The modalities of follow-up (frequency of consultations and
      interest of repeated radiological examinations) of patients presenting with
      glandular metastases of melanoma (stage III of the AJCC classification) have not
      reached a consensus. PATIENTS AND METHODS: Since 1995, we have proposed clinical
      follow-up every two months and radiological controls with a thoracic-abdominal
      pelvic scan every 4 months, to patients at high risk of relapse for the early
      screening of an infra-clinical relapse. RESULTS: The median follow-up was of 16
      months (range: 1 to 82 months). Eight patients out of 24 (33 p. 100) followed-up
      in this manner, had asymptomatic metastases discovered by the radiological
      examinations. Among these 8 patients, three presented with a an operable, single,
      metastatic localization and two patients underwent surgery. One patient relapsed
      3 months later, the other was still alive without relapse 24 months later.
      DISCUSSION: Surgery remains the treatment of choice for all stages of melanoma.
      In the absence of clearly effective treatment of metastatic melanoma, the early
      discovery of an infra-clinical metastatic relapse presents two major advantages.
      The first is the discovery of a single, operable metastasis, as was the case in
      two of the patients out of 24. The second is to be able to suspend an eventual
      adjuvant therapy with interferon alpha, as soon as a relapse has been discovered.

PMID- 14576605
TI  - [1801-2001: two centuries of dermatology and venereology in the Assistance
      Publique-Hopitaux de Paris].
AB  - The specialization "Dermatology" was born at the Saint-Louis hospital in France
      in 1801, in the light of the revolutionary reforms that led to fundamental
      changes in the functioning of the hospitals in Paris. Hence, the Saint-Louis
      hospital occupies an eminent position in the history of dermatology in France,
      reinforced by the role of Jean-Louis Alibert, who founded the French school of
      Dermatology. Despite the place occupied by the physicians of the Saint-Louis
      Hospital in the creation and development of the French school of dermatology,
      other physicians in other hospitals contributed to the expansion of the
      dermatology school. The work of Pierre Rayer, in the nineteenth century, at the
      Saint-Antoine and subsequently the Charite hospitals, are within this scope. More
      recently, the re-organization of the Faculty of Medicine into University Hospital
      Centers has permitted the creation of various treatment, teaching and research
      centers within the structure of the public hospitals in Paris. From the start,
      syphilis was part of the Dermatology teaching and practice. In Paris, several so
      called "specialized" hospitals were created to house patients presenting with
      syphilis. Later on, the existence of these hospitals was questioned notably
      because of the constraints that their functioning imposed on the patients. Anti
      venereal care centers were developed in response to the request of the
      practitioners to facilitate the access to treatment.

PMID- 14576606
TI  - [Imatinib-induced purpuric vasculitis].
AB  - INTRODUCTION: Imatinib (Glivec) is a new molecule that specifically inhibits
      tyrosine-kinase activity and is used in the treatment of chronic myeloid
      leukemia. Cutaneous side effects with imatinib are frequent. We report the first
      case of purpuric vasculitis probably due to this drug. OBSERVATION: A 65 year-old
      man was treated for chronic myeloid leukemia with imatinib. After two months of
      treatment, he developed an erythematous and squamatous on the trunk, which
      regressed spontaneously one week after suspension of the product. Imatinib was
      reintroduced two months later. The patient immediately developed a painful,
      infiltrated, purpuric eruption on the legs. Histological examination revealed
      vasculitis compatible with the diagnosis of toxiderma. Since treatment could not
      be suspended, oral corticosteroids were introduced and the lesions cleared within
      three weeks. DISCUSSION: Adverse cutaneous reactions to imatinib are frequent.
      Their physiopathological mechanism is unknown.

PMID- 14576607
TI  - [Herpetic-like worsening of an epidermolysis bullosa simplex during pregnancy].
AB  - INTRODUCTION: Episodes of hereditary epidermolysis bullosa simplex are usually
      provoked by repeated cutaneous traumas or exposure to heat. We report a case of
      hereditary epidermolysis bullosa simplex worsened during pregnancy. OBSERVATION:
      A 21 year-old woman suffering from hereditary epidermolysis bullosa simplex
      presented with unusual symptoms in the form of an extensive vesicular-bullous
      eruption at two months of her first pregnancy. Standard histological examination
      revealed an eosinophilic infiltrate in the bullae. The global results of the
      initial examinations suggested a herpetic-like episode of epidermolysis bullosa
      as is observed during the Dowling-Meara form of the disease. DISCUSSION: Various
      physiopathological hypotheses can be advanced to explain the worsening of the
      eruption during pregnancy: a mechanical origin with scratching of pruritus,
      enhanced fragility of the inter-keratinocyte bridges secondary to edema provoked
      by salt-water retention or a loss in antigenic tolerance to muted keratins 5 and
      14, as in pemphigoid gestationis. The presence of eosinophils in the dermis and
      epidermis may also participate directly in the formation of bullae due to the
      release of cationic proteins.

PMID- 14576608
TI  - [Aleukemic monoblastic leukemia cutis].
AB  - BACKGROUND: The diagnostic and prognostic value of specific cutaneous lesions in
      acute leukemia is well-known. Paradoxically, these lesions may initially develop
      without peripheral blood or bone marrow involvement. We report the case of a
      patient with cutaneous lesions of acute monoblastic leukemia whereas peripheral
      blood was normal and massive infiltration of dermis was demonstrated.
      OBSERVATION: A 49 year-old man had papules and nodules of the back and upper arms
      evolving for several months. Histological examination with appropriate
      immunostaining led to the diagnosis of specific cutaneous lesions of acute
      monoblastic leukemia. Several hemograms with peripheral blood smears were normal,
      bone marrow smear demonstrated an important blastic infiltration on one site and
      a discrete infiltration on another. Cutaneous lesions disappeared with
      chemotherapy. DISCUSSION: Specific cutaneous lesions may be isolated during acute
      leukemia, and called aleukemic leukemia cutis. These are a rare form, the
      underlying mechanism of which relies on the accumulation of small quantities of
      myeloblasts in bone narrow and with high tropism for the dermis.

PMID- 14576609
TI  - [Pachydermatodactyly associated with plantar pachydermy].
AB  - INTRODUCTION: Pachydermodactyly is a superficial fibromatosis located on the
      proximal portion of fingers'phalanges and interphalangeal joints. Several types
      of this disease have been described depending on topography, etiology and
      pathological associations. We report a typical observation of pachydermodactyly
      associated with a plantar pachydermy. CASE-REPORT: A 19 year-old man was followed
      for a psychotic disease, associated with mental retardation. On clinical
      examination, he showed a typical pachydermodactyly, predominantly located on the
      second, third and fourth fingers of both hands, associated with recent
      acrocyanosis. A pachydermic aspect was also observed on the external part of the
      feet sole. Histopathological analysis was identical on digital and plantar
      lesions with collagen swelling. These lesions extended into the subcutaneous fat
      only in the feet. DISCUSSION: This observation is compatible with the most
      classical form of pachydermodactyly which involves several fingers of both hands,
      usually in men. Furthermore, the association with a psychiatric disorder and the
      notion of repeated traumatisms have been frequently reported in the literature.
      However, acrocyanosis and the important disability observed in our case are
      unusual. Association with plantar pachydermy has never been reported. The
      identical histological aspect on finger and feet sole suggests that
      pachydermatodactyly should be integrated in framework of acral pachydermy.

PMID- 14576610
TI  - [Subcutaneous mycosis due to Scopulariopsis brevicaulis in an aplasic patient].
AB  - INTRODUCTION: Among the filamentous fungi of the Hyphomycete class, Annellospore
      group, the Scopulariopsis genera presently includes 16 species considered as
      opportunist pathogens. We report some unusual cutaneous manifestations due to
      Scopulariopsis brevicaulis in an immunodepressed patient. OBSERVATION: A 67 year
      old man presented with a lymphomatous form of Waldenstrom's macroglobulinemia.
      During chemotherapy with medullar aplasia, inflammatory cutaneous nodules
      appeared on the forearm and leg. Microbiological and histological examinations
      identified Scopulariopsis brevicaulis. The patient improved with rapid remission
      from aplasia using hematopoietic growth factors and treatment with itraconazole.
      COMMENTS: In a patient in medullar aplasia, the rapid onset of an extra-ungual
      cutaneous localization (forearm and leg) of a Scopulariopsis brevicaulis
      infection, without systemic involvement, suggests that the cutaneous inoculation
      occurred through scratching (from the nails) or from another cutaneous origin.
      Prolonged neutropenia enhanced the pathogenicity of this mycosis. The mycological
      and histological examinations are fundamental to confirm the diagnosis.

PMID- 14576611
TI  - [Prevention of aspirin-induced angioedema with an association of leukotriene
      inhibitors and antihistamines].

PMID- 14576612
TI  - [Doxycycline: in reply to Jean-Marie Bonnetblanc].

PMID- 14576613
TI  - [Post-traumatic ulcerations].

PMID- 14576614
TI  - [A papular nodule on the forehead].

PMID- 14576615
TI  - [Allergy to iodine].

PMID- 14576616
TI  - [Lichen].

PMID- 14576617
TI  - [Two types of errors].

PMID- 14576618
TI  - [Addisonian hyperpigmentation].

PMID- 14576619
TI  - [What must be done to improve the quality of antibiotic therapy in health care
      centers?].

PMID- 14576622
TI  - Lowering plasma homocysteine.

PMID- 14576620
TI  - [Rofecoxib-induced aquagenic edema with puckering of the palms of the hands: the
      first case].

PMID- 14576623
TI  - Iodine-131 tositumomab (bexxar) for treatment of lymphoma.

PMID- 14576624
TI  - Alpha-L-iduronidase (laronidase; aldurazyme).

PMID- 14576625
TI  - Adolescent sex education: making it a priority.

PMID- 14576626
TI  - Environmental health of children.
AB  - Pediatric primary health care providers are responsible for providing
      comprehensive care to children. This includes assessing for and identifying the
      effect of environmental hazards on children's health and managing conditions that
      may result from exposure to environmental toxins. This article begins by
      reviewing the unique developmental, biologic, and behavioral characteristics of
      children and age-specific issues that make them particularly vulnerable to
      toxins. It then provides the reader with general assessment and management
      strategies related to environmental toxins, including an assessment tool that can
      be used in a pediatric primary care office. The qualities of selected toxins that
      have been implicated in childhood illnesses are discussed. Routes of exposure,
      signs and symptoms of toxicity, and assessment and management approaches are
      presented specifically for lead, mercury, environmental tobacco smoke,
      particulate matter, asbestos, radon, molds, and pesticides. Because prevention is
      the best intervention in environmental health, the article emphasizes ways
      pediatric providers can work with caregivers to prevent or minimize exposure.

PMID- 14576628
TI  - Childhood immunizations: a parent education and incentive program.
AB  - This article describes some strategies to help reduce the immunization barriers
      of parental knowledge deficits and transportation costs through a parent
      education and incentive program. A record review of 471 children in 22 licensed
      Norfolk, Virginia, day-care centers revealed that 141 (29.9%) had inadequate age
      appropriate immunizations. Educational programs included depictions of
      preventable communicable diseases and their consequences. Upon completion of
      appropriate immunizations, parents received transportation vouchers and gifts. By
      June 2000, 255 parents, day-care administrators, teachers, and staff had
      participated in educational programs and seven day-care centers earned
      certificate awards for improved immunization rates among enrollees. Four centers
      had 100% age-appropriate immunization rate, and three had a rate of 92% to 95%.

PMID- 14576627
TI  - Integrating healthy steps into PNP graduate education.
AB  - INTRODUCTION: The purpose of this project was to explore a) the value of an
      adapted version of the Healthy Steps program for Pediatric Nurse Practitioner
      (PNP) graduate students and b) the perceptions of PNP program directors regarding
      practice issues, educational preparation and the Healthy Steps program. METHOD: A
      four-part workshop was offered to students in their final year of the program.
      Outcomes were measured through evaluations and a pre-test/post-test design. A
      survey was also mailed to 24 PNP program directors. RESULTS: More than 90% of the
      participating students rated this workshop as "good or excellent." All of the
      students recommended integration of Healthy Steps content into PNP graduate
      education. PNP program directors voiced concern about the effect of the managed
      care environment on PNP practice, acknowledged the importance of strengthening
      health supervision visits, and expressed interest in the Healthy Steps program.
      DISCUSSION: This project demonstrated that an adapted version of the Healthy
      Steps program enhanced the education of final year PNP students. PNP program
      directors expressed concern about practice issues, preparation for practice, and
      would consider potential adoption of portions of the Healthy Steps curriculum.

PMID- 14576629
TI  - Promoting safety of young children with guided participation processes.
AB  - The infant's complete dependence on others for protection and the young child's
      desire to explore the world puts them in harm's way without the caregiver's
      vigilance and commitment to practices that promote safety. Using a car seat,
      placing an infant in the supine position for sleep, and watching and monitoring a
      child's activities within the home are just a few of the safety practices
      required of a young child's caregiver. Safety information alone may not be
      adequate to develop a caregiver's competencies for safe practice. A process of
      clinician-caregiver co-participation to support competency development for
      current and future caregiving safety practice is described for clinicians who are
      in a position to support development of these competencies, including public
      health nurses and nurse practitioners.

PMID- 14576630
TI  - Pediatric HIV medication adherence: the views of medical providers from two
      primary care programs.
AB  - INTRODUCTION: The purpose of this study was to examine medical providers' views
      from two primary care programs regarding adherence to antiretroviral therapy
      among HIV-infected children. METHOD: Ten medical providers (five physicians and
      five registered nurses) working with perinatally HIV-infected children completed
      a structured questionnaire examining provider-patient/family relationship and
      participated in an individual qualitative interview regarding providers' views on
      pediatric adherence to antiretroviral therapy. RESULTS: Providers believed that
      the limited treatment options currently available to HIV-infected children
      presented families with tremendous challenges to adherence. Most children were
      prescribed difficult treatment regimens and needed increasingly complex regimens
      for possible success in the future, placing further demands on the adherence
      issue. Although providers were able to identify several helpful communication
      strategies in theory, they were not able to consistently implement them in
      practice. Further, many families are also struggling with poverty, mental health
      and substance use problems, additional HIV disease in the family, and disclosure
      issues. DISCUSSION: Adherence to antiretroviral therapy is a long-term, ongoing
      problem that is directly tied to the family life of the HIV-infected child.
      Providers clearly play an integral part in this struggle.

PMID- 14576631
TI  - Evaluation and management of childhood idiopathic (immune) thrombocytopenia.

PMID- 14576632
TI  - A toddler with hepatomegaly.

PMID- 14576635
TI  - What's new in infant formulas?

PMID- 14576634
TI  - Research considerations with children and adolescents.

PMID- 14576636
TI  - President's message: to infinity and beyond.

PMID- 14576637
TI  - NAPNAP position statement on credentialing and privileging for pediatric nurse
      practitioners.

PMID- 14576638
TI  - Atypical generalized eruptive histiocytosis associated with acute monocytic
      leukemia.
AB  - Histiocytoses are diseases caused by proliferation of either dendritic
      cells/Langerhans cells or of monocytes/macrophages. Generalized eruptive
      histiocytosis belongs to the cutaneous non-Langerhans cell histiocytoses and is a
      rare monocyte-macrophage proliferative disorder that usually follows a benign
      clinical course. We present the case of a 59-year-old man who presented with a 7
      month history of progressively developing erythematous macules and slightly
      elevated papules widely distributed over the trunk, neck, face, and thighs.
      Ultrastructurally, no Birbeck granules were observed, and immunochemistry did not
      reveal any S-100 protein or CD1a antigen in any of the lesional cells, excluding
      Langerhans cell histiocytosis. In addition, the histiocytic infiltrate in the
      skin of our patient was shown to strongly express MS-1 high molecular weight
      protein, a marker described as highly characteristic for cutaneous non-Langerhans
      cell histiocytoses. Bone-marrow smear examination and flow cytometric analysis
      revealed monocytic leukemia. This is the second report of generalized eruptive
      histiocytosis associated with acute monocytic leukemia. We discuss the
      differential diagnoses of the clinical picture and stress that this benign
      cutaneous disorder may indicate an underlying hematologic malignancy.

PMID- 14576639
TI  - Darier's disease associated with an underlying neoplasm in combination with a
      nodular fibroproliferative disease.
AB  - Darier's disease is an autosomal dominant disease that typically arises during
      the first or second decades of life. It involves the abnormal keratinization of
      the epidermis, mucosa, and nails. We describe a 74-year-old man with metastatic
      carcinoma in whom fibroproliferative disease and an acquired variant of Darier's
      disease developed, both of which may have been paraneoplastic processes.

PMID- 14576640
TI  - Late-onset Papillon-Lefevre syndrome without alteration of the cathepsin C gene.
AB  - Mutations in the cathepsin C gene have recently been detected in Papillon-Lefevre
      syndrome (PLS). Until now, 5 cases with the late-onset variation of this disease
      have been reported in the literature. The genetic background of this type of PLS
      is still unknown. We describe a 46-year-old woman with late-onset transgredient
      palmar hyperkeratosis and a 10-year history of severe periodontal disease.
      Histology of skin biopsy specimens revealed a psoriasiform pattern. Dental
      examination showed severe gingival inflammation with loss of alveolar bone.
      Dental plaque investigated by a polymerase chain reaction method revealed DNA
      signals of 5 different dental bacteria. DNA from EDTA blood was investigated for
      mutations in the cathepsin C gene by polymerase chain reaction analysis and
      direct sequencing. A silent variation in the codon for proline-459 was detected
      but interpreted as a polymorphism of this gene. All genetic linkage and mutation
      studies for PLS performed so far have shown that PLS is genetically homogeneous.
      Our patient with late-onset variation of PLS, however, did not show a mutation in
      the cathepsin C gene. Thus, we suspect that there is another genetic cause for
      the late-onset forms of PLS.

PMID- 14576641
TI  - Hyperpigmentation in Chediak-Higashi syndrome.
AB  - We describe a 4 1/2 -year-old Saudi Arabian boy born to consanguineous parents
      who was initially seen with gradual onset of fever and abdominal distention. The
      patient was found to have speckled hypopigmentation and hyperpigmentation of the
      sun-exposed areas. The finding of large cytoplasmic granules in blood and bone
      marrow leukocytes established the diagnosis of Chediak-Higashi syndrome. We
      review the literature on this finding, which might be underreported, especially
      in darkly pigmented races.

PMID- 14576642
TI  - Leukoderma associated with Sezary syndrome: a rare presentation.
AB  - We describe a patient with Sezary syndrome who was initially seen with the rare
      occurrence of both generalized erythroderma and extensive leukoderma of his lower
      limbs. Apart from the absence of melanocytes in the leukodermic skin,
      histopathologic features of both areas were identical, showing an infiltrate of
      atypical lymphocytes with epidermotropism. This form of Sezary syndrome
      associated leukoderma is clinically distinguishable from hypopigmented mycosis
      fungoides in which hypopigmented lesions are the sole manifestation of the
      cutaneous T-cell lymphoma.

PMID- 14576643
TI  - Acquired progressive lymphangioma.
AB  - Acquired progressive lymphangioma is a very rare disorder that presents in
      childhood or early adolescence as a lymphatic proliferation that gradually
      enlarges. It most commonly involves an extremity and is typically characterized
      as an indurated plaque that may be brownish-red, violaceous, or yellow. We report
      the case of a 15-year-old boy with a 10-year history of acquired progressive
      lymphangioma on the sole.

PMID- 14576644
TI  - Widespread metastatic eccrine porocarcinoma.
AB  - Eccrine porocarcinoma is a rare malignant sweat gland tumor arising from the
      acrosyringium. These lesions can show multiple epidermotropic metastases,
      however, systemic spread is rare. We describe the case of a 42-year-old African
      American man who presented in February 1998 with a lesion on the plantar surface
      of his right foot that was diagnosed as an eccrine porocarcinoma. Subsequently,
      during the next year, cutaneous metastases developed to his left shoulder and
      flank. Two years after his initial presentation, he was admitted with an
      esophageal mass and multiple gastric ulcers. Biopsy specimens of these lesions
      demonstrated metastatic eccrine porocarcinoma. Further evaluation revealed
      multiple metastases to lymph nodes, lungs, and brain. Histologic examination
      revealed nests of basaloid cells with eosinophilic cytoplasm and intracellular
      ductlike lumina lined by eosinophilic basement membranelike material. These
      ductular structures where highlighted by immunohistochemical stains for
      carcinoembryonic antigen, confirming their eccrine differentiation. There were
      mitotic figures and individual cell necrosis. Although rare, systemic metastases
      from an eccrine porocarcinoma must enter the differential diagnoses of a tumor
      mass in such patients.

PMID- 14576645
TI  - Extramedullary plasmacytoma in cardiac transplant recipients.
AB  - Extramedullary plasmacytomas are an immunoproliferative, monoclonal disease of B
      cell lineage and are classified as non-Hodgkin's lymphomas. Cutaneous
      extramedullary plasmacytomas are rare. We report 2 cases of transplantation
      associated cutaneous extramedullary plasmacytomas in a setting of chronic
      immunosuppression.

PMID- 14576646
TI  - Facial erythema as a result of benzophenone allergy.
AB  - Benzophenones are common causes of photoallergy and are increasingly used in
      products other than traditional sunscreens. Patients may be unaware of any
      sunscreen exposure when using a product such as shampoo containing benzophenone.
      Benzophenones also may produce photoallergic contact urticaria, in addition to
      delayed contact and photocontact dermatitis, which may complicate the clinical
      presentation. Allergy to benzophenone should be considered in the diagnosis of
      patients with patchy erythema of the face and neck that is not typically
      eczematous and that may otherwise be attributed to a rosacea diathesis, lupus
      erythematosis, or simple flushing. Patch and photopatch testing are indicated to
      evaluate these patients for allergy to benzophenone.

PMID- 14576647
TI  - Ocular and cutaneous squamous cell carcinoma in an African American man with
      epidermodysplasia verruciformis resulting in blindness and death.
AB  - Epidermodysplasia verruciformis (EV) is a hereditary disease that has served as a
      model for viral-induced carcinogenesis. Patients with EV have an increased
      susceptibility to infection with human papillomavirus, which results in the
      development of benign lesions in childhood. The lesions may resemble tinea
      versicolor in appearance and distribution, and usually remain benign. However,
      later in life cutaneous squamous cell carcinoma may develop on sun-exposed areas,
      such as the forehead. Radiation therapy may not only result in the malignant
      conversion of EV lesions, but may also increase the risk of metastases. To our
      knowledge, this is the first report of a patient with EV in whom squamous cell
      carcinoma of the conjunctiva developed. His clinical course was complicated by
      ocular invasion causing blindness, metastasis, and eventually death.

PMID- 14576648
TI  - Pseudoxanthoma elasticum: Temporary treatment of chin folds and lines with
      injectable collagen.
AB  - Pseudoxanthoma elasticum is characterized by calcification of dermal connective
      tissues. Typical rhytides and horizontal creases of the chin are cutaneous
      manifestations that begin at an early age and are often overlooked. We report 2
      patients with pseudoxanthoma elasticum who had characteristic rhytides and
      horizontal creases of the chin ("mental" creases). Rhytides and horizontal
      creases were successfully treated with injectable collagen.

PMID- 14576649
TI  - Stevens-Johnson syndrome associated with ciprofloxacin: a review of adverse
      cutaneous events reported in Sweden as associated with this drug.
AB  - Stevens-Johnson syndrome is a severe mucocutaneous reaction, which can be
      elicited by various drugs. We present 2 cases with this syndrome associated with
      ciprofloxacin treatment and review the adverse cutaneous events reported as
      possibly related to ciprofloxacin treatment in Sweden between 1988 and 2000.
      Eight cases, excluding ours, of Stevens-Johnson syndrome, toxic epidermal
      necrolysis, and erythema multiforme were reported. This implies an annual
      incidence of these adverse cutaneous events of 0.045 per 100,000 treated patients
      (assuming an average treatment length of 10 days). One patient died, but
      ciprofloxacin was not considered to be the major cause of death. Together with
      previous data from the literature, our report supports the view that
      ciprofloxacin can cause severe adverse cutaneous events.

PMID- 14576650
TI  - Arcuate plantar plaques as the initial sign of chronic cutaneous lupus in a
      child.
AB  - A 9-year-old girl was initially seen with bilateral mildly pruritic plantar skin
      lesions. Skin biopsy demonstrated a superficial and deep perivascular lymphoid
      infiltrate with mucin but was not specific. Laboratory evaluation revealed a
      mildly elevated antinuclear antibody and mild leukopenia. Over the following
      year, an annular skin lesion developed in the preauricular area, her antinuclear
      antibody titer rose, and she was found to have positive anti-SS-B antibodies. She
      responded to oral hydrochloroquine with resolution of her skin lesions. This
      report highlights the unusual presentation of a case of chronic cutaneous lupus
      with a plantar skin eruption.

PMID- 14576652
TI  - Infliximab for the treatment of hidradenitis suppurativa.
AB  - We describe a patient with hidradenitis suppurativa whose lesions responded to
      the administration of infliximab for suspected Crohn's disease.

PMID- 14576651
TI  - Demodex abscesses: clinical and therapeutic challenges.
AB  - A 53-year-old man had a 6-week history of confluent erythematous papules,
      pustules, and abscesses of the face initially limited to the right nasolabial
      fold. Histologic investigation revealed a perifollicular infiltrate with
      lymphocytes, histiocytes, and many Demodex folliculorum mites. A large number of
      mites were seen in skin scrapings. The skin manifestations progressed and
      persisted for the following 5 years and were unresponsive to numerous
      antiparasitic treatments, including repeated oral administration of ivermectin
      and external application of lindane, permethrin, and benzoyl benzoate. Therapy
      with oral administration of 250 mg metronidazole 3 times a day for 2 weeks
      resulted in rapid and lasting recovery. Demodex folliculitis remains a diagnostic
      and therapeutic challenge. Antiparasitic therapies used against lice or scabies
      may fail in control of D folliculorum mites. In the presence of clinical and
      microscopic findings typical of Demodex folliculitis or abscesses, treatment
      failure with acaricidal agents does not exclude the diagnosis. Oral metronidazole
      seems to work in the management of this chronic mite infestation.

PMID- 14576653
TI  - Pyoderma gangrenosum in a patient with collagenous colitis.
AB  - The association between pyoderma gangrenosum and inflammatory bowel disease is
      well established. Collagenous colitis is one of the microscopic colitides, which
      are thought to be on the same spectrum of disease as Crohn's disease and
      ulcerative colitis. Before this study there had been no reported cases of
      pyoderma gangrenosum in the setting of collagenous colitis. We report a case of a
      79-year-old woman with symptomatic collagenous colitis and refractory pyoderma
      gangrenosum.

PMID- 14576654
TI  - Idiopathic eruptive macular pigmentation: a case of 21 years' duration.
AB  - Idiopathic eruptive macular pigmentation is a rare condition characterized by
      asymptomatic pigmented macules involving the neck, trunk, and proximal portions
      of the extremities. Age at onset usually varies from 1 to 20 years. The lesions
      usually appear abruptly and remit spontaneously over months to years. An unusual
      case of a 24-year-old woman with idiopathic eruptive macular pigmentation lasting
      21 years was characterized by several periods of spontaneous resolution followed
      by recurrences.

PMID- 14576655
TI  - Hypocomplementemic urticarial vasculitis with angioedema, a rare presentation of
      systemic lupus erythematosus: rapid response to rituximab.
AB  - We report a case of hypocomplementemic urticarial vasculitis and recurrent
      angioedema in a patient with systemic lupus erythematosus unresponsive to
      mycophenolate mofetil, high-dose methylprednisolone, and intravenous
      immunoglobulin that responded rapidly to rituximab. Rituximab is a monoclonal
      antibody against CD20 transmembrane protein on the surface of mature and
      malignant B cells. No adverse effects occurred during or after therapy, and the
      patient was discharged from the hospital for outpatient rituximab infusion and
      follow-up care.

PMID- 14576656
TI  - Traumatic pseudoaneurysm of the superficial temporal artery: two cases and review
      of the literature.
AB  - Aneurysms of the facial vasculature have been reported since the mid-seventeenth
      century from a variety of accidental, violent, and surgical injuries. Of the 386
      cases of facial aneurysm reported in the world literature, 327 involve the
      superficial temporal artery. The nomenclature is somewhat confusing, because
      pseudoaneurysms are often referred to as simply "aneurysms" in the literature.
      Given that superficial temporal artery pseudoaneurysms might be seen in the guise
      of a cyst or lipoma, it is imperative that the dermatologist be aware of their
      presentation. To date, there have been 7 cases reported in the dermatologic
      literature. We report 2 additional cases of traumatic superficial temporal artery
      pseudoaneurysm and review the dermatologic literature.

PMID- 14576657
TI  - Instruments and new technologies for the in vivo diagnosis of melanoma.
AB  - The principal objective of screening individuals at risk for melanoma is
      detection of cutaneous melanoma during the curable stages of its early evolution.
      Unaided visual inspection of the skin is often suboptimal at diagnosing melanoma.
      Improving the diagnostic accuracy for melanoma remains an area of active
      research. These research efforts have focused on both the detection of early
      melanoma and the in-depth evaluation of suspicious pigmented lesions for the
      presence or absence of melanoma. Numerous instruments are under investigation to
      determine their usefulness in imaging and ascertaining a correct in vivo
      diagnosis of melanoma. It is anticipated that some of these tools, alone or in
      combination, will improve our ability to differentiate, in vivo, melanoma from
      its simulators. Ultimately, these advances may prevent unnecessary biopsies
      (increased specificity) while increasing the sensitivity for diagnosing melanoma.
      This article reviews the current instruments and new technologies for the in vivo
      diagnosis of melanoma. Learning objective At the conclusion of this learning
      activity, participants should be acquainted with the instruments designed to
      facilitate the early detection of melanoma. They should also be familiar with the
      basic technology behind these instruments and should recognize the potential
      benefits and limitations inherent in each.

PMID- 14576658
TI  - Topical bexarotene therapy for patients with refractory or persistent early-stage
      cutaneous T-cell lymphoma: results of the phase III clinical trial.
AB  - OBJECTIVES: We sought to determine the safety and efficacy of topical bexarotene
      (Targretin; Ligand Pharmaceuticals, La Jolla, Calif) gel 1% in patients with
      refractory or persistent early-stage cutaneous T-cell lymphoma. METHODS: We
      conducted a multinational, open-label, phase III study of 50 patients with stage
      IA to IIA cutaneous T-cell lymphoma. The primary end point classification was the
      overall complete and partial response rate by the higher of 2 measures: the
      Physician's Global Assessment of Clinical Condition or the Composite Assessment
      of Index Lesion Disease Severity. RESULTS: The overall response rates for the
      Physician's Global Assessment of Clinical Condition, Composite Assessment of
      Index Lesion Disease Severity, and primary end point classification were 44%,
      46%, and 54%, respectively. The most common adverse events possibly related to
      study medication were mild to moderate irritant dermatitis, pruritus, pain (ie,
      primarily burning at application site), and skin disorder (eg, skin inflammation,
      excoriation, and new lesions). There were no serious treatment-related adverse
      events. CONCLUSIONS: Topical bexarotene gel was generally well tolerated and
      demonstrated substantial efficacy in patients with refractory or persistent early
      stage cutaneous T-cell lymphoma.

PMID- 14576659
TI  - CD4+ T-cell-directed antibody responses are maintained in patients with psoriasis
      receiving alefacept: results of a randomized study.
AB  - BACKGROUND: Alefacept, human LFA-3/IgG(1) fusion protein, selectively reduces
      memory-effector (CD45RO(+)) T cells, a source of the pathogenic mediators of
      psoriasis. OBJECTIVE: To evaluate the effect of alefacept on immune function, T
      cell-dependent humoral responses to a neoantigen (PhiX174) and recall antigen
      (tetanus toxoid) were assessed. METHODS: Patients with psoriasis were randomized
      to the control group or to receive alefacept (7.5 mg intravenously weekly for 12
      weeks). The alefacept group received PhiX174 immunizations at weeks 6, 12, 20,
      and 26 and tetanus toxoid at week 21; control subjects received PhiX174 at weeks
      6 and 12 and tetanus at week 10. RESULTS: Mean anti-PhiX174 titers were
      comparable in both groups. There was no difference in the percentage of
      responders (anti-PhiX174 IgG >/=30% of the total anti-PhiX174) between the
      alefacept group and the control group (86% and 82%, respectively; P =.73). The
      percentage of patients with anti-tetanus toxoid titer increases >/=2 times
      baseline also was similar (alefacept, 89%; control 91%). CONCLUSION: A single 12
      week course of alefacept did not impair primary or secondary antibody responses
      to a neoantigen or memory responses to a recall antigen. The selective
      immunomodulatory effect of alefacept against a potentially pathogenic T-cell
      subset is associated with maintenance of a significant aspect of immune function
      (antibody response) to fight infection and respond to vaccinations.

PMID- 14576660
TI  - Injection site reactions with the HIV-1 fusion inhibitor enfuvirtide.
AB  - BACKGROUND: Enfuvirtide is the first of a new class of antiretroviral agents for
      the treatment of HIV-1 infection, called the fusion inhibitors. The most common
      type of adverse event associated with enfuvirtide treatment is injection site
      reactions, occurring in up to 98% of patients. Many of these lesions are
      symptomatic. This study investigated injection site reactions occurring in 7
      patients with HIV infection who were receiving enfuvirtide. OBSERVATIONS: All
      biopsy specimens revealed an inflammatory response consistent with a localized
      hypersensitivity reaction; this was regardless of type of clinical lesion and
      included the patient with no clinical reaction. The pattern of inflammation
      resembled that of granuloma annulare and the recently described interstitial
      granulomatous drug reaction. Immunoperoxidase staining indicated that the
      inflammatory and collagen changes were greatest in areas where enfuvirtide was
      deposited. CONCLUSIONS: The pathologic changes and clinicopathologic correlations
      associated with injection site reactions in human enfuvirtide recipients have
      been described for the first time. This information also provides valuable
      insights into unusual pathogenic response to foreign antigens for patients with
      HIV.

PMID- 14576661
TI  - Epidemiology of primary Merkel cell carcinoma in the United States.
AB  - BACKGROUND: Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer.
      OBJECTIVE: We sought to describe primary MCC incidence trends, epidemiology, and
      predictors of survival. METHODS: The population covered by the Surveillance,
      Epidemiology, and End Results Program was analyzed as a prospective cohort. We
      measured age-adjusted incidence rates (per 100,000 person-years) and effect of
      age, anatomic site, and stage on survival. RESULTS: Incidence was higher in males
      (0.34) than in females (0.17). Cases (n = 1034) occurred mostly in whites (94%),
      in people older than 65 years (76%), and at the head (48%). The 5-year relative
      survival was 75%, 59%, and 25% for localized, regional, and distant MCC,
      respectively. Female sex, limb presentation, localized disease, and younger age
      were positive predictors of survival. CONCLUSION: The highest incidence of MCC
      was observed in whites, males, and in people older than 65 years. Only 49% of
      cases were reported as localized. Better survival was associated with limb
      localization, early-stage disease, younger age, and female sex.

PMID- 14576663
TI  - Lichen planus associated with hepatitis C virus: no viral transcripts are found
      in the lichen planus, and effective therapy for hepatitis C virus does not clear
      lichen planus.
AB  - BACKGROUND: Although hepatitis C virus (HCV) was not discovered until 1989, it
      was recognized for many years that a viral agent was responsible for many cases
      of posttransfusion or parenterally transmitted hepatitis. Acute HCV is often
      relatively mild; however, 70% to 80% of patients with HCV go on to develop
      chronic liver disease during a prolonged period of up to 40 years, and up to 50%
      of them may remain relatively asymptomatic during that time. A number of
      associated cutaneous findings have been reported in up to 15% of these patients
      including lichen planus-like eruptions (LP). OBJECTIVE: We sought to determine
      whether viral transcripts were present within the skin of patients with HCV and
      LP, and if systemic virologic response to interferon alfa and ribavirin
      correlated with response of the LP. Materials and methods A total of 4 men and 1
      woman all presented with cutaneous eruptions of LP, and 1 had oral LP lesions.
      Cutaneous biopsies were performed on all patients. All patients were found to
      have chronic HCV. In addition to pathologic examination, immunohistochemical
      stains for lymphoid markers and reverse-transcriptase polymerase chain reaction
      for HCV was performed on the biopsy specimens. All patients were treated with
      interferon alfa and ribavirin. RESULTS: In LP there were scattered eosinophils
      seen in biopsy specimens of 4 of the 5 patients. The lymphoid infiltrate
      contained predominantly CD3(+) T cells and scattered KP-1(+) mononuclear cells,
      without CD20(+) B cells. Approximately one fourth of the T cells failed to mark
      with CD4. Although all patients were seropositive for HCV RNA at the time of
      biopsy, we were unable to detect HCV RNA by reverse-transcription polymerase
      chain reaction in any of the patients. The patients' LP showed an inconsistent
      response to therapy. CONCLUSION: The virus was not found in the LP lesion using
      reverse-transcription polymerase chain reaction for HCV. Thus, LP appears to be
      related to the pattern of immune dysregulation induced by HCV, probably in a host
      with an underlying susceptibility for autoimmune disease. The combination of
      interferon alfa and ribavirin may be effective in clearing the virus, but viral
      response did not correlate with clearing of LP.

PMID- 14576662
TI  - Prevalence and characterization of uremic pruritus in patients undergoing
      hemodialysis: uremic pruritus is still a major problem for patients with end
      stage renal disease.
AB  - BACKGROUND: Pruritus is a common disabling problem in patients with advanced end
      stage renal disease. Few studies have evaluated the clinical characteristics of
      uremic itch. OBJECTIVES: The aim of this multicenter study was to provide a
      comprehensive description of the prevalence and clinical characteristics of
      pruritus affecting patients with end-stage renal disease who are undergoing
      hemodialysis. METHODS: A detailed questionnaire recently developed was used to
      evaluate pruritus in 219 patients undergoing hemodialysis treatment in 3 dialysis
      units. We examined the relationship of the quality of dialysis and various
      factors and medical parameters to itch. RESULTS: Pruritus was a common symptom in
      the study population. Approximately 66% of the patients had pruritus at some
      point, and 48% were affected by it at the time of the study. There was no
      correlation between the occurrence of pruritus and demographic or medical
      parameters (type of kidney disease, medical management, dialysis efficacy as
      expressed by Kt/V) of the patient. The data suggest that uremic pruritus tends to
      be prolonged, frequent, and intense, and it can impair the patient's quality of
      life including a negative effect on sleep and mood. Major factors found to
      exacerbate pruritus include rest, heat, dry skin, and sweat. Major factors found
      to reduce pruritus include activity, sleep, hot and cold shower, and cold.
      Treatment with angiotensin inhibitors seemed to be more common among those with
      uremia who had itch (P =.02) whereas furosemide was more commonly used among
      those who never itched (P =.002). CONCLUSION: This study provides a detailed
      description of uremic pruritus with new data on its characteristics including
      affective and sensory dimensions and associated symptoms.

PMID- 14576664
TI  - Hair transplanting: an important but often forgotten treatment for female pattern
      hair loss.
AB  - The techniques used in the early days of hair transplanting were not suitable for
      the treatment of a majority of women with pattern hair loss. For at least the
      last 10 years, changes in those techniques have resulted in a reversal of that
      situation. Today, many women with female pattern hair loss are suitable
      candidates for transplanting, however, this is not widely appreciated. This
      article provides potential explanations for this and demonstrates examples of the
      current methods. Hair transplanting should be considered as a potential treatment
      option for most women with pattern hair loss.

PMID- 14576665
TI  - The effect of antibiotic therapy for patients infected with Helicobacter pylori
      who have chronic urticaria.
AB  - BACKGROUND: Several small trails looking at antibiotic therapy targeted at
      Helicobacter pylori for the treatment of chronic urticaria have been published
      and have had conflicting results. We conducted a systematic review of existing
      studies to help answer the clinical question of whether this therapy has a role
      in the treatment of chronic urticaria. METHODS: We identified studies published
      in the English language with searches of MEDLINE, PREMEDLINE, American College of
      Physicians Journal Club, Database of Abstracts of Reviews of Effectiveness, and
      Cochrane Libraries using the key words "Helicobacter pylori" and "urticaria."
      Relevant studies from bibliography reviews were also included. Studies included
      met the following criteria: (1) patients had urticaria for at least 6 weeks; (2)
      other known causes of urticaria were excluded by appropriate testing; (3) the
      initial diagnosis of H pylori infection was made by either serology, urea breath
      test, or upper endoscopy; and (4) an adequate trial of an antibiotic with known
      activity against H pylori was completed. RESULTS: In all, 10 studies met our
      inclusion criteria. The rate of remission of urticaria when H pylori was
      eradicated was 30.9% (59/191) compared with 21.7% (18/83) when H pylori was not
      eradicated; the background remission rate among control subjects without H pylori
      infection was 13.5% (10/74). When data from the 10 studies were combined,
      eradication of H pylori was both quantitatively and statistically associated with
      remission of urticaria (odds ratio 2.9; 95% confidence interval 1.4-6.8; P
      =.005). CONCLUSION: We found that resolution of urticaria was more likely when
      antibiotic therapy was successful in eradication of H pylori infection than when
      patients who were infected did not achieve eradication. These results suggest
      that clinicians, after considering other causes of urticaria, should constitute
      (1) testing for H pylori; (2) treating with appropriate antibiotics if H pylori
      is present; and (3) confirming successful eradication of infection.

PMID- 14576666
TI  - PTEN expression in normal skin, acquired melanocytic nevi, and cutaneous
      melanoma.
AB  - BACKGROUND: Although various studies have shown mutations of the tumor suppressor
      gene, PTEN/MMAC1, in primary, metastatic, and cultured cutaneous melanoma
      specimens, little is known about the pattern of PTEN protein expression in early
      melanocytic tumor progression. OBJECTIVE: To further investigate the role of PTEN
      in melanocytic tumor development. METHODS: We assessed the level and distribution
      of PTEN in normal skin, 39 acquired melanocytic nevi, and 30 primary cutaneous
      melanomas, including lentigo malignas, by immunostaining. RESULTS: We found high
      levels of PTEN expression in cutaneous muscles, nerves, and muscular arteries,
      and moderate-to-high amounts of PTEN in the epidermis, follicular epithelium, and
      sebaceous and eccrine glands. PTEN staining in cutaneous lymphatics, dermal and
      periadnexal adventitial fibroblasts, and chondrocytes were variably absent.
      Junctional melanocytes and chondrocytes frequently exhibited preferential nuclear
      staining. We found uniformly strong PTEN expression in the cytoplasm of almost
      all benign and dysplastic nevi. However, there was some evidence of nuclear PTEN
      loss even in the benign melanocytic proliferations. In addition, out of 30
      primary cutaneous melanomas and lentigo malignas, we detected diffuse expression
      of PTEN in 11 (37%) tumors, widespread loss of PTEN in 11 (37%) tumors and mixed
      PTEN expression in 8 (27%) lesions. In the primary cutaneous melanomas, PTEN was
      largely localized to the cytoplasm. CONCLUSIONS: The presence of PTEN in benign
      melanocytic tumors and the absence of PTEN in a significant proportion of primary
      cutaneous melanomas support a role for PTEN loss in the pathogenesis of melanoma.

PMID- 14576667
TI  - Low-dose methotrexate to treat mycosis fungoides: a retrospective study in 69
      patients.
AB  - BACKGROUND: Although low-dose methotrexate has been used to treat mycosis
      fungoides for many years, documentation is very limited. OBJECTIVE: Our purpose
      was to review our experience with methotrexate in the treatment of 69 patients
      with patch/plaque and tumor stage mycosis fungoides observed for up to 201
      months. METHODS: This was a retrospective study. Data are presented in terms of
      response rates and time to treatment failure. RESULTS: The greatest number of
      patients (60) had patch/plaque stage T2 disease (>/=10% skin involved). Of these,
      7 (12%) achieved complete remission and 13 (22%) achieved partial remission for a
      total response rate of 20 of 60 (33%). The median time to treatment failure was
      15 months. Only 1 of 7 patients with tumor stage disease responded. Side effects
      caused treatment failure in 6 (9%) of the total cohort of 69 patients.
      CONCLUSION: Low-dose methotrexate may be of value in the treatment of a subset of
      patients with patch/plaque mycosis fungoides resistant to other therapies.

PMID- 14576668
TI  - Pulsed dye laser treatment of thick/raised vascular lesions using compression
      with clear plastic.

PMID- 14576669
TI  - Incidence of side effects after laser hair removal.
AB  - BACKGROUND: Despite the widespread use of lasers for hair removal there are few
      data published on the incidence of side effects from this treatment. OBJECTIVE:
      The aim of this study was to generate data on a large number of patients
      receiving laser hair removal to obtain an accurate assessment of the incidence
      and type of side effects resulting from treatment. METHODS: A multicenter
      prospective study of patients presenting for laser hair removal was conducted to
      determine incidence of side effects in relation to skin type and laser or lasers
      used. RESULTS: Laser hair removal is associated with a low incidence of side
      effects that are self-limiting in the majority of cases. The highest incidence of
      side effects was seen in patients with darker skin treated with the long-pulsed
      ruby laser. CONCLUSIONS: Laser hair removal is inherently safe. For darker
      Fitzpatrick skin types the long-pulsed neodymium:yttrium-aluminum-garnet laser is
      preferred to the ruby laser.

PMID- 14576670
TI  - Cutaneous reactive angiomatoses: patterns and classification of reactive vascular
      proliferation.
AB  - New and relatively old types of vascular (capillary) proliferations in the skin
      have been described or better categorized in the last few years. They include
      reactive angioendotheliomatosis, acroangiodermatitis (pseudo-Kaposi sarcoma),
      diffuse dermal angiomatosis, intravascular histocytosis, glomeruloid
      angioendotheliomatosis, and angiopericytomatosis (angiomatosis with
      cryoproteins). Clinically, all of them present with multiple, erythematous
      violaceous and purpuric patches and plaques, sometimes evolving toward necrosis
      and ulceration with a wide distribution but a propensity to involve limbs.
      Histologically, they are characterized by different patterns of intravascular or
      extravascular lobular or diffuse hyperplasia of endothelial cells, pericytes, and
      sometimes histiocytes. Although these angioproliferations can histologically
      mimic vascular tumors, they are reactive in that they seem to originate from the
      occlusion of vascular lumina by different localized or systemic disorders and the
      vascular proliferation stops after the inducing hypoxic stimulus has been
      withdrawn. In this article, the authors review all these forms of reactive
      angioproliferations in the skin, suggest a novel title, cutaneous reactive
      angiomatoses, and propose a unifying pathogenetic mechanism.

PMID- 14576671
TI  - AAD consensus statement on psoriasis therapies.

PMID- 14576672
TI  - Medical pearl: cytodiagnosis for subepidermal calcified nodule.

PMID- 14576673
TI  - Surgical pearl: use of sterile glove finger as a surgical drain.

PMID- 14576674
TI  - Mondor's disease: a rare cause of anterior chest pain.
AB  - We report the case of a 52-year-old patient who sought a rheumatologic
      consultation for anterior chest pain of 2 weeks' duration. Radiology for trauma
      did not reveal any pathology. The laboratory findings focusing on rheumatologic
      diseases remained unhelpful and no abnormalities were found. After a cutaneous
      linear cordlike lesion at the right lateral chest wall occurred, the diagnosis of
      Mondor's disease could be made on the basis of clinical and histologic
      investigation. Because pain precedes the typical clinical manifestation, problems
      of diagnosis can occur in the early phase of the illness.

PMID- 14576675
TI  - Localization of Sweet's syndrome in radiation-induced locus minoris resistentae.
AB  - Sweet's syndrome is a reactive dermatosis clinically characterized by fever,
      leukocytosis, and multiple, erythematous, painful plaques. Histopathologically,
      the lesions show edema of the papillary dermis and a dermal infiltrate mainly
      composed of neutrophils, without vasculitis. We describe a patient with breast
      carcinoma and Sweet's syndrome mostly involving previously irradiated skin.

PMID- 14576676
TI  - Milker's nodule in a healthy young woman.
AB  - Milker's nodules (pseudocowpox) are harmless skin lesions most commonly seen in
      persons whose occupation regularly brings them into close contact with cattle.
      They are caused by the paravaccinia virus, a member of the poxvirus family.
      Awareness of their clinical and histopathologic features is important, especially
      with today's heightened awareness of the threat of biologic warfare, to
      distinguish them from more worrisome entities such as tularemia and anthrax.

PMID- 14576677
TI  - Hematoma-like metastasis in melanoma.
AB  - Three years after removal of a primary tumor, spontaneous hematoma developed on
      the anterior aspect of the chest of a 33-year-old woman. Ultrasound examination
      verified by histologic findings indicated subcutaneous metastasis. This new type
      of metastasis with characteristic clinical features has not been mentioned in the
      literature, and we named it "hematoma-like metastasis." Special care should be
      taken in examining patients with melanoma and spontaneous hematoma.

PMID- 14576678
TI  - Kaposi's varicelliform eruption in a patient with Grover's disease.
AB  - Kaposi's varicelliform eruption is a secondary herpes simplex virus infection
      that affects patients in the setting of primary dermatologic conditions. It
      occurs with a variety of skin diseases, although association with Grover's
      disease has never been reported in the literature. This report describes the
      manifestations and clinical course. A review of the literature on Kaposi's
      varicelliform eruption includes disease associations, pathogenesis, and
      treatment.

PMID- 14576679
TI  - Sclerosing lymphangitis of the penis.
AB  - Nonvenereal sclerosing lymphangitis is a rare penile lesion consisting of a
      minimally tender, indurated cord involving the coronal sulcus and occasionally
      adjacent distal penile skin. This disorder most often occurs after vigorous
      sexual activity and resolves spontaneously. However, as evidenced by 2 of the 3
      cases reported, this condition also may be associated with underlying sexually
      transmitted disease that necessitates specific therapy.

PMID- 14576680
TI  - Dermal endothelial cells express eotaxin in hypereosinophilic syndrome.
AB  - We describe a patient with hypereosinophilic syndrome, who had severe cutaneous
      eruptions. Immunohistochemical study revealed that dermal endothelial cells in
      the lesional skin of this patient expressed eotaxin, which indicates eotaxin
      plays a part in inducing eosinophil migration into cutaneous tissue in
      hypereosinophilic syndrome.

PMID- 14576681
TI  - Necrobiosis lipoidica of the glans penis.
AB  - We report a 65-year-old diabetic man with necrobiosis lipoidica occurring on the
      glans of penis. He was initially seen with chronic ulcerative balanitis that
      eventually healed with strict control of diabetes mellitus, cystostomy, and
      pentoxifylline, leaving heavily depressed scars. Penile necrobiotic palisading
      granulomas include necrobiosis lipoidica and granuloma annulare. On the basis of
      the literature review, these 2 diseases manifest different skin lesions.

PMID- 14576682
TI  - Dermal melanocytic proliferation with features of a plaque-type blue nevus and
      neurocristic hamartoma.
AB  - Blue nevi (BN) and neurocristic hamartomas (NCH) are pigmented lesions that
      originate from the aberrant development of cells derived from the neural crest.
      BN are composed of dermal melanocytes, whereas NCH have a broader histology and
      show Schwann cell differentiation as well. In addition, BN and NCH might differ
      in their potential to develop into a malignancy. We describe a patient with a
      lesion showing features of both a plaque-type BN and NCH.

PMID- 14576683
TI  - Whorled scarring alopecia: a rare phenomenon in incontinentia pigmenti?
AB  - Incontinentia pigmenti is a rare X-linked dominant disease that affects the
      ectodermal tissues and is usually lethal in males. Two girls, 1 Malay and 1
      Chinese, with incontinentia pigmenti of the Bloch-Sulzberger type had a whorled
      pattern of scarring alopecia. This phenomenon, hitherto unreported in association
      with this disorder, corresponded to the lines of Blaschko. The mother and
      maternal grandmother of the Malay girl also had whorled scarring alopecia. This
      phenomenon is permanent and can be used as a marker to ascertain affected adult
      women who may no longer have cutaneous manifestations. X chromosome inactivation
      in females during early embryogenesis results in a mosaic population of cells,
      which explains the linear and patchy cutaneous manifestations of incontinentia
      pigmenti.

PMID- 14576684
TI  - Fatal squamous cell carcinoma arising from transplant-associated porokeratosis.
AB  - Porokeratosis is a disorder of epidermal keratinization characterized by variably
      sized plaques with central depression and a well-demarcated keratotic border.
      Associations of porokeratosis with immunosuppression and of porokeratosis with
      malignancy have been observed. The authors report a case of fatal metastatic
      squamous cell carcinoma arising from porokeratosis in an immunosuppressed
      patient.

PMID- 14576685
TI  - Epidermoid cyst with perforation of the skull.
AB  - A rare case of an epidermoid cyst associated with a skull defect is reported. The
      patient was a 59-year-old healthy woman from Japan who exhibited an elastic,
      soft, subcutaneous tumor on the left side of the parietal scalp for approximately
      10 years without a history of trauma. On radiographic findings, a punched-out
      lesion was shown. Computed tomography of the cranium revealed a mass on the left
      parietal side that adhered to the cerebrum through the bone defect. Surgical
      excision resulted in remission. The tumor was peridurally located and showed no
      adhesion to the dura mater encephali. Histopathologically, a hybrid epidermoid
      cyst with no malignant features was seen. We hypothesized that long-term
      continuous pressure by the cyst resulted in a bone defect called scalloping.

PMID- 14576686
TI  - Topical methotrexate for lymphomatoid papulosis.
AB  - Lymphomatoid papulosis is a lymphoproliferative disease characterized by
      recurrent papules, nodules, or plaques that spontaneously involute within several
      weeks. Despite having a histologically malignant-appearing infiltrate, patients
      with lymphomatoid papulosis have a clinically benign course. Several treatment
      options have been described for the management of lymphomatoid papulosis. We
      describe a patient who had complete resolution of lesions with the use of topical
      methotrexate.

PMID- 14576687
TI  - Beryllium dermatitis.
AB  - Chronic beryllium disease is a granulomatous disorder characterized by a cell
      mediated immune response to beryllium. Most reports of chronic beryllium disease
      discuss pulmonary and noncutaneous immunologic findings. This report of
      occupational chronic beryllium disease emphasizes cutaneous findings and
      discusses the potential role of skin exposure in the disease.

PMID- 14576688
TI  - Primary mucinous carcinoma in a 54-year-old man.
AB  - Primary mucinous carcinoma is a rare malignant tumor that most frequently occurs
      in the periorbital area. This tumor originates from the deepest portion of the
      eccrine sweat duct. This normally asymptomatic and slow-growing tumor has
      demonstrated a local recurrence rate of 30% after excision with narrow surgical
      margins and can have local metastases. It is difficult to differentiate this
      tumor histologically from metastatic lesions. Immunohistochemical staining and
      cytokeratin profiles have been studied to aid in the differentiation between
      primary lesions and metastatic mucinous carcinomas. We present a case of a 54
      year-old man with recurrent primary eccrine mucinous carcinoma and review the
      clinical, histologic, and immunohistochemical features of this tumor.

PMID- 14576689
TI  - Primary cutaneous coccidioidomycosis.
AB  - Primary cutaneous coccidioidomycosis is usually secondary to laboratory or
      autopsy inoculation, but can result from trauma in endemic areas. We describe an
      unusual case of primary inoculation cutaneous coccidioidomycosis occurring in an
      immunocompetent woman in a nonendemic area. The clinical features, diagnostic
      tests, and therapy of this extremely rare disease are reviewed.

PMID- 14576690
TI  - Short anagen hair with persistent synchronized pattern of scalp hair growth.
AB  - Unlike other mammals that molt hair seasonally, human beings have scalp hair
      follicles that exhibit an asynchronized pattern of cycling, with the growth and
      subsequent shedding of each hair being independent of others around it. This
      mosaic cycling behavior is established early and continues throughout life. We
      describe a boy who continues to have a synchronized pattern of hair growth and
      shedding, and a short anagen duration at 4 years of age. He appears to never have
      established the expected asynchronized pattern of hair growth.

PMID- 14576691
TI  - Orofacial granulomatosis in a patient with Crohn's disease.
AB  - Orofacial granulomatosis encompasses the previously recognized clinical entities
      Melkersson-Rosenthal syndrome and cheilitis granulomatosa. We report the case of
      a 39-year-old patient with cheilitis granulomatosa, intestinal Crohn's disease,
      and optic neuropathy. Cheilitis granulomatosa and optic neuropathy represent 2
      rare manifestations of orofacial granulomatosis in Crohn's disease.

PMID- 14576692
TI  - Adoption of new technologies for early detection of melanoma in dermatologic
      practice.
AB  - The identification and diagnosis of early melanoma will reduce unnecessary
      operations and may be important in reducing mortality from melanoma and impacting
      cost savings to the health system. New technologies are being developed and used
      at some specialized centers to facilitate the detection and diagnosis of early
      melanoma for patients at high risk. These technologies include but are not
      limited to digital photography, dermoscopy, computerized image analysis systems,
      and confocal scanning laser microscopy. To most effectively implement these novel
      approaches, it is important to identify the key factors that influence the
      adoption or diffusion of new medical technologies. We propose patient-, physician
      , and health care system-related factors that influence the diffusion of new
      technologies for the early detection of skin cancer. Studies involving physicians
      and patients in a variety of clinical settings need to be conducted to achieve a
      greater understanding of the barriers to the adoption of these new technologic
      tools that are intended to aid in skin cancer screening.

PMID- 14576693
TI  - Ultraviolet autorepigmentation in scleroderma.

PMID- 14576695
TI  - X-linked ichthyosis in southern Italy.

PMID- 14576694
TI  - Bilharziasis cutanea tarda: a rare presentation of schistosomiasis.

PMID- 14576696
TI  - A case of erythema elevatum diutinum associated with antiphospholipid antibodies.

PMID- 14576697
TI  - Lidocaine patch helpful in managing the chronic pain of leg ulceration.

PMID- 14576698
TI  - Cutaneous infections with herpes simplex virus and tacrolimus ointment.

PMID- 14576699
TI  - Treatment of vitiligo with limited resources in Bangladesh.

PMID- 14576700
TI  - Conflict of interest statement.

PMID- 14576707
TI  - Ways dietitians of different generations can work together.

PMID- 14576708
TI  - Interim report of the State Issues Task Force.

PMID- 14576709
TI  - Complementary and alternative medicine: competencies for dietetics professionals.

PMID- 14576710
TI  - Nutrition diagnosing and order writing: value for practitioners, quality for
      clients.

PMID- 14576711
TI  - Development and implementation of a visual card-sorting technique for assessing
      food and activity preferences and patterns in African American girls.
AB  - OBJECTIVE: Card-sorting tasks for assessing food and activity preferences and
      patterns among African American girls were developed. Associations among food
      preference and intake frequency, activity preference and frequency, and body mass
      index were examined. DESIGN: Participants completed newly developed card-sorting
      tasks assessing food and activity preferences and patterns. Height and weight
      were measured. SUBJECTS/SETTING: Ninety-six 8- to 10-year-old African American
      girls from schools and community centers in Minneapolis-St. Paul. MAIN OUTCOME
      MEASURES: Preference and frequency data for 64 foods/beverages and 34 activities.
      STATISTICAL ANALYSES: Frequencies for food and activity preference and frequency
      categories were computed. Pearson correlations among food and activity
      preference, frequency, and body mass index were computed. RESULTS: High-sugar
      (eg, fruit drinks, soda) and/or high-fat (eg, ice cream, cookies) foods were
      among the most popular and frequently consumed. Ninety-six percent of girls liked
      fruit drinks, with 35% consuming them "almost every day." Less-structured
      activities such as biking, games, jump rope, and dance were most popular. Biking
      was preferred by 85% of girls, with 48% biking "almost every day." Food
      preference and frequency categories were moderately correlated (r=0.30 to 0.58),
      as were activity preference and frequency (r=0.37 to 0.49). APPLICATIONS: The
      card-sorting tasks are useful tools for assessing food and activity preferences
      and patterns in girls. Obesity prevention programs for African American girls
      should include preferred activities such as dance, jump rope, and active play.
      Programs may also benefit from a focus on replacing high fat/high sugar snacks
      and sweetened beverages with low-fat, lower-calorie snacks and beverages (eg,
      fruit, vegetables, water).

PMID- 14576712
TI  - Food habits are associated with lipid peroxidation in an elderly population.
AB  - OBJECTIVE: The purpose of this study was to assess the association between
      dietary intake and lipid peroxidation. DESIGN: Cross-sectional population
      analysis from an ongoing prospective study. Malondialdehyde (MDA) was measured as
      a marker of lipid peroxidation. Diet was assessed through direct observation and
      food frequency questionnaire. SUBJECTS: Participants with no missing data were
      162 nonsmoking elderly individuals residing in 7 institutions across Asturias
      (Spain). STATISTICAL ANALYSES PERFORMED: Comparisons of adjusted group means by
      tertiles of plasma MDA were made by analysis of variance. Stepwise regression
      analysis was done using MDA as a dependent variable and food intake as an
      independent variable. Food intakes were categorized into quartiles and logistic
      regression was applied to calculate the odds ratio for being in the highest
      tertile of plasma MDA. RESULTS: Consumption of potatoes had an independent direct
      effect and accounted for a sizeable proportion of the variation in plasma MDA
      levels (18%, P<.001). In addition to potatoes, other foods that had an apparently
      independent effect on plasma MDA were eggs, cooked vegetables, and red wine
      (R(2)=0.028, 0.023 and 0.018, respectively). In this study, dietary factors
      accounted for 25% of the variation in plasma MDA levels. CONCLUSION: Identifying
      nutritional determinants of oxidative stress is important because of its negative
      health effect. Consumption of cooked vegetables and moderate intake of wine has
      been shown to be appropriate for reducing the risk of oxidative damage. On the
      contrary, caution must be used with the intake of potatoes because we have found
      a positive association with MDA levels. Further studies are required to
      investigate the mechanism(s) of this association and whether it is related to the
      preparation method or to the potato itself.

PMID- 14576713
TI  - Did dietetics begin with the ADA or the cure of scurvy?

PMID- 14576714
TI  - A video lesson series is effective in changing the dietary intakes and food
      related behaviors of low-income homemakers.
AB  - OBJECTIVE: To examine the relative cost-effectiveness of a self-administered
      video series in delivering nutrition education to low-income homemakers. DESIGN:
      A quasi-experimental design was used, with subjects randomly assigned to
      traditional lessons (Traditional Group) or video lessons (Video Group).
      SUBJECTS/SETTING: 108 subjects were recruited, with 93 nonpregnant, low-income,
      female homemakers completing the study (response rate = 86%). Subjects had
      recently enrolled in the Expanded Food and Nutrition Education Program, or the
      Food Stamp Nutrition Education Program, and had a videocassette recorder and
      telephone. INTERVENTION: Both groups received 12 lessons from the Eating Right Is
      Basic Series, 3rd edition, with the Traditional Group being taught in face-to
      face sessions and the Video Group receiving self-administered, video-lesson
      packets. OUTCOME MEASURES: Dietary intake and food behaviors were assessed at pre
      and post intervention with 24-hour recalls and a 14-item checklist. STATISTICAL
      ANALYSES: Chi(2) and t tests were used to compare the groups on demographics and
      pre-intervention dietary factors. Multiple analysis of variance was used for
      comparisons of change from pre to post intervention. RESULTS: Significant
      improvements were observed in both groups for fruits, calcium, and vitamins A and
      C. The Video Group improved on fiber intake (P<or=.005). The groups did not
      differ on dietary or behavior change (P=.2357). Duplication and implementation
      costs of the video series totaled 4,820 dollars, or 36% of the traditional lesson
      cost of 13,463 dollars. APPLICATIONS: Both methods achieved similar improvements
      in diet and behaviors, but the video method was less expensive. The video series
      seems to be a cost-effective method for delivering nutrition education to low
      income homemakers.

PMID- 14576715
TI  - Low dietary quality among older adults with self-perceived ill-fitting dentures.
AB  - OBJECTIVE: To examine dietary quality and nutrient intakes of participants
      wearing dentures with and without poor fit as determined by questionnaire and
      dental exam. DESIGN: Nutrient intakes, Healthy Eating Index (HEI) score, and
      serum nutrient values were examined among individuals wearing either adequate- or
      poor-fitting dentures and individuals who had at least 18 teeth.
      SUBJECTS/SETTING: Data was collected from 4,820 participants in the Third
      National Health and Nutrition Examination Survey ages 50 years and older with at
      least 18 teeth (n=3,207) or those wearing dentures (n=1,613), who responded to a
      questionnaire about denture fit and had their dentures evaluated by a dentist.
      STATISTICAL ANALYSES PERFORMED: Analysis of covariance and multivariate linear
      regression analyses were used to examine associations between individuals fully
      dentate, wearing good-or ill-fitting dentures, and nutritional status indicators.
      RESULTS: The group with self-perceived ill-fitting dentures compared with the
      group with natural teeth had significantly lower total HEI (66.5 vs 68.5 P<.002),
      vegetables (6.3 vs 6.8 P<.01), and variety scores (7.8 vs 8.2 P<.02); lower
      ascorbic acid (P<.009) and carotene intakes (P<.004). The group with self
      perceived good-fitting dentures did not differ significantly from the dentate
      group. However, both groups wearing dentures had significantly lower serum levels
      of vitamins C and E, beta carotene, folate, lutein, and lycopene/zeaxanthin
      compared with the dentate group. APPLICATIONS/CONCLUSIONS: Dietary quality and
      intake of certain nutrients was poorer among the group with self-perceived ill
      fitting dentures than among those wearing adequate dentures or those with natural
      teeth. Administering a simple questionnaire to patients about their perceptions
      of denture fit may be useful in identifying denture wearers at increased risk of
      dietary inadequacy.

PMID- 14576716
TI  - Nonvitamin, nonmineral supplement use over a 12-month period by adult members of
      a large health maintenance organization.
AB  - OBJECTIVE: National survey data show an increase in the prevalence of nonvitamin,
      nonmineral (NVNM) supplement use among adults over the past 10 years. Concern
      over this trend is based in part on reports of potential drug-supplement
      interactions. The type and prevalence of supplement use by demographic and
      behavior characteristics were examined among members of a large group model
      health plan, including those with selected health conditions. DESIGN: Data on the
      use of herbal medicines and dietary supplements among survey respondents were
      analyzed. Questions employed a checklist for six specific NVNM supplements with
      optional write-ins. SUBJECTS/SETTING: A stratified random sample of 15,985 adult
      members of a large group model health maintenance organization in northern
      California, who were respondents to a 1999 general health survey. STATISTICAL
      ANALYSES PERFORMED: Analyses were conducted with poststratification weighted data
      to reflect the actual age, gender, and geographic distribution of the adult
      membership from which the sample was drawn. RESULTS: An estimated 32.7% of adult
      health plan members used at least one NVNM supplement. The most frequently used
      herbs were Echinacea (14.7%) and Gingko biloba (10.9%). Use of all NVNM
      supplements was highest among females, 45 to 64 years of age, whites, college
      graduates, and among those with selected health conditions. APPLICATIONS:
      Dietetics professionals need to uniformly screen clients for dietary supplement
      use and provide accurate information and appropriate referrals to users.

PMID- 14576717
TI  - An examination of at-home food preparation activity among low-income, food
      insecure women.
AB  - A secondary analysis of data from a study of nutritional vulnerability among 153
      women in families seeking charitable food assistance was undertaken to estimate
      the extent and nutritional significance of at-home food preparation activity for
      these women. At-home food preparation was estimated from women's reported food
      intakes from three 24-hour recalls. The relationships between food preparation
      and energy and nutrient intake, food intake, and 30-day household food security
      status were characterized. Almost all participants (97%) consumed foods prepared
      from scratch at least once during the three days of observation; 57% did so each
      day. Both the frequency and complexity of at-home food preparation were
      positively related to women's energy and nutrient intakes and their consumption
      of fruits and vegetables, grain products, and meat and alternates. The intakes by
      women in households with food insecurity with hunger reflected less complex food
      preparation but no less preparation from scratch than women in households where
      hunger was not evident, raising questions about the extent to which food skills
      can protect very poor families from food insecurity and hunger. Our findings
      indicate the need for nutrition professionals to become effective advocates for
      policy reforms to lessen economic constraints on poor households.

PMID- 14576718
TI  - Food mixture or ingredient sources for dietary calcium: shifts in food group
      contributions using four grouping protocols.
AB  - Identifying dietary sources of nutrients by assigning survey foods to food groups
      can under- or overestimate the contribution a group makes to the intake of
      specific nutrients. Using calcium and food intakes from USDA's 1994-1996, 1998
      Continuing Survey of Food Intakes by Individuals, the authors determined the
      proportion of dietary calcium from the dairy, grains, meats, fruits, and
      vegetables groups using four grouping protocols. Calcium contributions from milk
      and cheese were higher as more ingredient sources and fewer survey food items
      were represented in the dairy group. Milk, cheese, and yogurt reported as
      separate survey food items contributed 42% of total calcium intake. An additional
      21% of dietary calcium came from dairy ingredients in mixed foods such as
      macaroni and cheese, pizza, sandwiches, and desserts. The remaining dietary
      calcium sources were single grains (16%); vegetable (7%); meat, poultry, and fish
      (5%); fruit (3%); and miscellaneous foods (7%). Data quantifying the nutrient
      contributions from dairy ingredients could affect dietary guidance messages or
      research using dairy foods as variables.

PMID- 14576719
TI  - Dietetic technicians report low to moderate levels of burnout.
AB  - This study identified and described the status of burnout experienced by dietetic
      technicians (DTRs) in various settings. A questionnaire was sent to a random
      sample of 300 members from the American Dietetic Association's (ADA's) Dietetic
      Technician in Practice practice group. The Maslach Burnout Inventory-Human
      Services Survey was used to measure burnout. On the emotional exhaustion
      subscale, the respondents reported a mean score of 20.6 (high level of burnout
      >27), 5.3 on the depersonalization subscale (high level of burnout >14), and 38.6
      on the personal accomplishment subscale (high level of burnout <30). These
      results suggest that the DTRs as a group perceive themselves to be moderately
      emotionally exhausted, to have a low level of depersonalization, and to have a
      high level of personal accomplishment. Further analysis also suggests that DTRs
      in nontraditional settings experience more personal accomplishment than those in
      traditional healthcare and foodservice settings.

PMID- 14576720
TI  - Decision-making patterns for dietary supplement purchases among women aged 25 to
      45 years.
AB  - Women frequently consume dietary supplements but the criteria used to select
      supplements have received little investigation. This research identified the
      decision-making criteria used for dietary supplements among women aged 25 to 45
      years who consumed a supplement at least four times per week. Participants (N=51)
      completed an in-store shopping interview that was audiotaped, transcribed, and
      analyzed qualitatively for the criteria used to make supplement selections.
      Qualitative analysis revealed 10 key criteria and the number of times each person
      used each criterion was quantified. Cluster analysis identified five homogeneous
      subgroups of participants based on the criteria used. These included brand
      shopper, bargain shopper, quality shopper, convenience shopper, and information
      gatherer. Supplement users vary in the criteria used to make point-of-purchase
      supplement selections. Dietetics professionals can classify supplement users
      according to the criteria used to tailor their nutrition counseling and better
      meet the educational needs of consumers.

PMID- 14576721
TI  - Environmental and behavioral factors are associated with the calcium intake of
      low-income adolescent girls.
AB  - Based on social cognitive theory, the purpose of this study was to determine
      whether selected environmental and behavioral factors were associated with the
      calcium intake of low-income adolescent girls. Teachers in three public middle
      schools administered a written survey resulting in data from 105 girls (the
      majority were Asian American). Calcium intake was lower than recommended and was
      associated with eating breakfast, number of children in the household,
      availability of some high-calcium foods, and seeing important others drink milk
      or being encouraged to drink milk. Educational interventions should be targeted
      to parents in relation to making affordable sources of calcium available and
      modeling adequate intake to adolescents.

PMID- 14576722
TI  - Measuring fruit and vegetable consumption: providing serving size information
      doubles estimated percent eating five per day.
AB  - Measuring the extent to which individuals meet the 5 A Day dietary recommendation
      for fruits and vegetables can provide information on the effectiveness of public
      health efforts to increase consumption of these foods. However, dietary
      measurement is complicated by the issue of serving size. We compared two methods
      of measuring fruit and vegetable consumption using a random-digit-dialed
      telephone survey of 917 Washington state adults. The survey included two sets of
      questions about fruit and vegetable consumption, one providing and the other not
      providing standard definitions of serving size. The specific wording of questions
      had a large effect on the conclusions about levels of fruit and vegetable
      consumption. Although only 26% of respondents met the 5 A Day recommendations
      without serving size information, 50% met these recommendations when using a
      measure that included a definition of serving size.

PMID- 14576723
TI  - Celiac diet: its impact on quality of life.
AB  - The objective of this study was to determine the effects of a gluten-free diet,
      examining food consumption and limitations on quality of life for those with
      celiac disease. Twenty-nine items on self-administered questionnaires queried
      demographics, lifestyle, and food use. Some items were from the Rand Survey (Rand
      Corporation, Santa Monica, CA). Most responses used three- or five-point Likert
      scales. They were mailed to members of the Westchester Celiac Sprue Support
      Group. Of the 274 responses, 253 were usable and were the basis of the compiled
      results. Seventy-four percent of the respondents were female; 42% were between
      the ages of 36 and 55 years of age, and 46% were more than 55 years of age.
      Frequencies and cross-tabulations indicated several areas of negative impact in
      maintaining a gluten-free diet. They included the difficulties of dining out
      (86%), travel (82%), and impact on family (67%) and less of a negative impact on
      career or work (41%). The gluten-free diet impacted various lifestyle aspects of
      the quality of life for individuals with celiac disease.

PMID- 14576724
TI  - Ruby P. Puckett, MA, RD, FCSI, CFE receives 2003 Copher Memorial Award.

PMID- 14576728
TI  - What kids say they do and what parents think kids are doing: The ADAF/Knowledge
      Networks 2003 Family Nutrition and Physical Activity Study.

PMID- 14576730
TI  - Comparative analysis of T-cell receptor gene rearrangements at diagnosis and
      relapse of T-cell acute lymphoblastic leukemia (T-ALL) shows high stability of
      clonal markers for monitoring of minimal residual disease and reveals the
      occurrence of second T-ALL.
AB  - A total of 28 children and nine adults with relapsed T-ALL were analyzed for the
      configuration of their T-cell receptor (TCR) and TAL1 genes at diagnosis and
      relapse to evaluate their stability throughout the disease course. A total of 150
      clonal TCR and TAL1 gene rearrangements were identified in the 37 patients at
      diagnosis. In 65% of cases all rearrangements and in 27% of cases most
      rearrangements found at diagnosis were preserved at relapse. Two children with
      unusually late T-ALL recurrences displayed completely different TCR gene
      rearrangement sequences between diagnosis and relapse. This indicates that a
      proportion of very late T-ALL recurrences might represent second T-ALL.
      Specifically, 88% of clonal rearrangements identified at diagnosis in truly
      relapsed T-ALL were preserved at relapse. This is significantly higher as
      compared to previously studied precursor-B-ALL ( approximately 70%). Thus, from
      biological point of view, immunogenotype of T-ALL is more stable as compared with
      precursor-B-ALL. The overall stability of TCR gene rearrangements was higher in
      adult T-ALL (97%) than in childhood T-ALL (86%). Based on the stability of TCR
      gene rearrangements, we propose a strategy for PCR target selection (TCRD+TAL1 -
      > TCRB --> TCRG), which probably allows reliable minimal residual disease
      detection in all T-ALL patients.

PMID- 14576732
TI  - Adult lymphoblastic lymphoma: a retrospective analysis of 92 patients under 61
      years included in the LNH87/93 trials.
AB  - Since 1987, the GELA has initiated multicenter prospective trials for aggressive
      non-Hodgkin's lymphomas (NHL). Lymphoblastic lymphomas (LBL) were included in
      those studies until 1997, and 92 LBL patients under 61 years were identified
      after histological review. The protocols prescribed high-dose anthracycline
      regimens, four cycles given every 15 days as induction and lasted for </=6
      months. A total of 23 patients underwent high-dose therapy consolidation followed
      by autologous stem-cell transplantation and 69 received standard chemotherapy
      regimens. Clinical characteristics showed a male predominance (66%) with a median
      age of 31 years, bone marrow (BM) involvement (22%), mediastinal involvement
      (66%) and elevated LDH (62%). At the end of treatment, it was seen that 71% of
      the patients achieved complete remission; four (4%) patients died during
      induction; 43 patients relapsed at a median time of 10 months. With a median
      follow-up of 34 months, the 5-year overall survival (OS) and event-free survival
      (EFS) rates were 32 and 22%, respectively. The only favorable factor
      significantly associated with survival was young age. These results are poorer
      than those obtained in other aggressive lymphomas treated with the same regimens
      and suggest that adult LBL patients should be treated with acute lymphoblastic
      leukemia protocols.

PMID- 14576731
TI  - Pretransplant minimal residual disease level predicts clinical outcome in
      patients with acute myeloid leukemia receiving high-dose chemotherapy and
      autologous stem cell transplantation.
AB  - A total of 31 adult patients with AML entered in the EORTC/GIMEMA AML-10 trial,
      who received autologous stem cell transplantation (ASCT) after induction and
      consolidation chemotherapy, were prospectively evaluated for minimal residual
      disease (MRD) by multidimensional flow cytometry (MFC). Using a cutoff level of
      3.5 x 10(-4) leukemic cells pre-ASCT, 12 patients (39%) were stratified to MRD
      high-risk group and 19 (61%) into MRD low-risk group. During follow-up, all
      patients who were in the high-risk group relapsed at a median time of 7 months;
      in the low-risk group, five patients relapsed at a median time of 11 months and
      14 remained in remission for 56 (range 7-80) months (P=0.00004). Longitudinal MFC
      determinations post-ASCT showed increased MRD levels in three of the five
      patients who underwent subsequent relapse, while disease recurrence was
      unpredicted in the remaining two cases. The pre-ASCT MRD status was the factor
      most strongly associated with relapse risk in the multivariate analysis
      (P=0.0014). We conclude that: (1) pre-ASCT MRD status predicts successful outcome
      in patients receiving ASCT; (2) high-dose chemotherapy conditioning regimen
      followed by ASCT has no impact on the unfavorable prognostic value of high pre
      ASCT MRD level; and (3) sequential MRD monitoring post-ASCT may allow the
      prediction of impending relapse.

PMID- 14576733
TI  - T-cell signaling and costimulatory molecules in B-chronic lymphocytic leukemia (B
      CLL): an increased abnormal expression by advancing stage.

PMID- 14576736
TI  - Microspatial structure of Drosophila melanogaster populations in Brazzaville:
      evidence of natural selection acting on morphometrical traits.
AB  - Two genetically distinct habitat races of Drosophila melanogaster coexist in
      Brazzaville (Congo). One is the typical field type of Afrotropical populations,
      the other mainly breeds in beer residues in breweries. These two populations
      differ in their ethanol tolerance, in their allelic frequencies at several enzyme
      and microsatellite loci and in the composition of their cuticular hydrocarbons.
      The brewery population is quite similar to European temperate populations with
      regard to all these traits. Previous investigations of two morphological traits
      (ovariole number and sternopleural bristle number) failed to detect any
      difference between the two habitat races. Here we investigated other
      morphological traits (wing and thorax length, thorax pigmentation and female
      abdomen pigmentation). The reaction norms of these traits according to growth
      temperature were compared in the two Afrotropical habitat races and in a French
      temperate population. As expected, the French population was very different from
      the field African population: as a general rule, the brewery population
      (Kronenbourg) was intermediate in several aspects between the other two. We
      conclude that the strong selective forces that maintain the genetic divergence
      between the two habitat races also act on morphometrical traits, and the possible
      selective mechanisms are discussed.

PMID- 14576737
TI  - Genetic neighbourhood of clone structures in eelgrass meadows quantified by
      spatial autocorrelation of microsatellite markers.
AB  - Limited dispersal distances in plant populations frequently cause local genetic
      structure, which can be quantified by spatial autocorrelation. In clonal plants,
      three levels of spatial organization can contribute to positive autocorrelation;
      namely, the neighbourhood of (a) ramets, (b) clone fragments and (c) entire
      clones. Here we use data from an exhaustive sampling scheme on a clonal plant to
      measure the contribution of the neighbourhoods of each distinct clonal structure
      to total spatial autocorrelation. Four plots (256 grid points each) within dense
      meadows of the marine clonal plant Zostera marina (eelgrass) were sampled for
      clone structure with nine microsatellite markers ( approximately 80 alleles). We
      found significant coancestry (f(ij)), at all three levels of spatial
      organization, even when not allowing for joins between samples of identical
      genets. In addition, absolute values of f(ij) and the maximum distance with
      significant positive f(ij) decreased with the progressive exclusion of joins
      between alike genotypes. The neighbourhood of this clonal plant thus consists of
      three levels of organization, which are reflected in different kinship
      structures. Each of these kinship structures may affect the level of biparental
      inbreeding and the physical distance between flowering shoots and their
      outcrossing neighbourhood. These results also emphasize the notion that spatial
      autocorrelation crucially depends on the scale and intensity of sampling.

PMID- 14576738
TI  - Genetics of quantitative traits in Arabidopsis thaliana.
AB  - The genetic control of 22 quantitative traits, including developmental rates and
      sizes, was examined in generations of Arabidopsis thaliana derived from the cross
      between the ecotypes, Columbia (Col) and Landsberg erecta (Ler). The data were
      obtained from three sets of families raised in the same trial: the 16 basic
      generations, that is, parents, F(1)'s, F(2)'s, backcrosses, recombinant inbred
      lines (RILs) and a triple test cross (TTC), the latter produced by crossing the
      RILs to Col, Ler and their F(1). The data were analysed by two approaches. The
      first (approach A) involved traditional generation mean and variance component
      analysis and the second (B), based around the RILs and TTC families, involved
      marker-based QTL analysis. From (A), genetic differences between Col and Ler were
      detected for all traits with moderate heritabilities. Height at flowering was the
      only trait to show heterosis. Dominance was partial to complete for all height
      traits, and there was no overdominance but there was strong evidence for
      directional dominance. For most other traits, dominance was ambidirectional and
      incomplete, with average dominance ratios of around 80%. Epistasis, particularly
      of the duplicate type that opposes dominance, was a common feature of all traits.
      The presence of epistasis must imply multiple QTL for all traits. The QTL
      analysis located 38 significant effects in four regions of chromosomes I, II, IV
      and V, but not III. QTL affecting rosette size and leaf number were identified in
      all four regions, with days to maturity on chromosomes IV and V. The only QTL for
      height was located at the expected position of the erecta gene (chromosome II; 50
      cM), but the additive and dominance effects of this single QTL did not adequately
      explain the generation means. The possible involvement of other interacting
      height QTL is discussed.

PMID- 14576739
TI  - Absence of geographical structure of chloroplast DNA variation in sallow, Salix
      caprea L.
AB  - In the present study, we have used PCR-RFLP markers to investigate the
      chloroplast DNA variation in 24 European populations of Salix caprea L. A subset
      of these populations has also been analysed with chloroplast microsatellites. The
      main feature of both markers is the absence of a clear geographic structure
      (G(ST(PCR-RFLP))=0.090, G(ST(microsatellites))=-0.017) and high levels of
      variation within populations. This lack of phylogeographic structure in S. caprea
      is suggested to be the consequence of the joint action of several factors: (i)
      presence of intermediate latitude refugia with large population sizes during the
      last glacial maximum, (ii) a high speed of recolonisation and dispersal ability,
      (iii) a high mutation rate and (iv) extensive hybridisation with other willow
      species. In addition to the S. caprea samples, a limited number of individuals
      from several other Salix species were also analysed with PCR-RFLP: S. cinerea, S.
      aurita, S. purpurea, S. atrocinerea, S. appendiculata, S. elaeagnos, S. fragilis
      and S. alba. Many of the haplotypes found in Salix caprea were also detected in
      S. cinerea, S. aurita, S. purpurea, S. atrocinerea and/ or S. appendiculata but
      not in S. alba, S. elaeagnos or S. fragilis. Our data suggest that hybridisation
      and gene flow have occurred within these two groups but not between them.

PMID- 14576740
TI  - Effects of seed bank disturbance on the fine-scale genetic structure of
      populations of the rare shrub Grevillea macleayana.
AB  - Dispersal in most plants is mediated by the movement of seeds and pollen, which
      move genes across the landscape differently. Grevillea macleayana is a rare, fire
      dependent Australian shrub with large seeds lacking adaptations for dispersal;
      yet it produces inflorescences adapted to pollination by highly mobile
      vertebrates (eg birds). Interpreting fine-scale genetic structure in the light of
      these two processes is confounded by the recent imposition of anthropogenic
      disturbances with potentially contrasting genetic consequences: (1) the unusual
      foraging behaviour of exotic honeybees and 2. widespread disturbance of the soil
      stored seedbank by road building and quarrying. To test for evidence of fine
      scale genetic structure within G. macleayana populations and to test the
      prediction that such structure might be masked by disturbance of the seed bank,
      we sampled two sites in undisturbed habitat and compared their genetic structure
      with two sites that had been strongly affected by road building using a test for
      spatial autocorrelation of genotypes. High selfing levels inferred from genotypes
      at all four sites implies that pollen dispersal is limited. Consistent with this,
      we observed substantial spatial clustering of genes at 10 m or less in the two
      undisturbed populations and argue that this reflects the predicted effects of
      both high selfing levels and limited seed dispersal. In contrast, at the two
      sites disturbed by road building, spatial autocorrelation was weak. This suggests
      there has been mixing of the seed bank, counteracting the naturally low dispersal
      and elevated selfing due to honeybees. Pollination between near neighbours with
      reduced relatedness potentially has fitness consequences for G. macleayana in
      disturbed sites.

PMID- 14576741
TI  - Test for a population expansion after a drastic reduction in population size
      using DNA sequence data.
AB  - Populations may, during their evolutionary history, go through drastic changes in
      population size due to bottlenecks or founder events upon colonization of new
      areas. This involves a subsample of haplotypes, causing the allele frequencies to
      be different from the original population. In addition, the period of recovery
      after a bottleneck can be of considerable length. If reproduction is unequal
      among individuals but random with regard to haplotype, large deviations from the
      patterns expected in a stable population may result. By means of computer
      simulation, I have analysed the patterns arising when populations undergo
      bottlenecks and then slowly recover, and used two new statistical tests for the
      detection of the bottleneck. A test based on the variance of the relative
      frequency of haplotypes had generally high power even at low sample size (n=25).
      This statistic was most powerful after very strong bottlenecks and lost power
      with increasing propagule size. A test based on the variance of the pairwise
      differences shows slightly less power. As expected, power was reduced when
      migration into the founder population was allowed from the source population.
      This suggests that the test is particularly suited for detecting relatively
      recent and strong bottlenecks, and thus may be a valuable tool for identifying
      population events on a fine temporal scale, such as colonisations after the last
      glaciation.

PMID- 14576743
TI  - Discrimination between selected lines of pigs using AFLP markers.
AB  - Amplified fragment length polymorphic (AFLP) markers were used to discriminate
      between lines of pigs, divergently selected over seven generations for components
      of efficient lean growth rate. A total of 270 animals with 30 animals per line
      were genotyped for 239 polymorphic AFLP markers. Canonical variate analysis
      identified linear combinations of the AFLP marker scores that grouped animals by
      selection line with no overlap between selection lines. Cluster analysis of AFLP
      marker scores identified 10 groups of animals with 226 of the 270 animals
      clustered into nine groups, each consisting of animals from only one selection
      line. AFLP marker genotyping, using the EcoRI and TaqI restriction enzymes,
      provided an effective means of discriminating between animals of different
      selection lines that have arisen from one base population.

PMID- 14576742
TI  - Population genetic structure of the malaria vector Anopheles minimus A in
      Vietnam.
AB  - Anopheles minimus A, a major malaria vector in Southeast Asia, is the main target
      of vector control in this area. The impact of these control measures can be
      influenced by the population structure of the target species. In rural areas, An.
      minimus breeds along the banks of small clear-water streams, yet in the suburbs
      of Hanoi, northern Vietnam, there is an An. minimus population whose immature
      stages develop in water tanks. This study uses allozyme data (1) to assess the
      population structure of An. minimus A and (2) to evaluate the taxonomic status of
      the urban An. minimus population from Hanoi. The population from the suburbs of
      Hanoi was identified as An. minimus A. Although significant genetic
      differentiation was observed between rural and urban An. minimus A populations,
      they have not differentiated substantially by genetic drift. Limited
      macrogeographical differentiation was observed between two rural populations at
      distances of more than 1000 km. Consequently, geographical distance is not the
      primary factor in differentiating An. minimus A populations having the typical
      breeding ecology. The estimated effective population size is consistent with the
      moderate macrogeographical differentiation. Furthermore, no genetic structuring
      was observed between adult mosquitoes having different behaviour. The
      macrogeographical population structure indicates that genes may spread over large
      areas, whereas the presence of an 'urban' An. minimus A population shows the
      ability of this species to adapt to anthropogenic environmental changes.

PMID- 14576744
TI  - Population genetics of sporophytic self-incompatibility in Senecio squalidus L.
      (Asteraceae) II: a spatial autocorrelation approach to determining mating
      behaviour in the presence of low S allele diversity.
AB  - We recently estimated that as few as six S alleles represent the extent of S
      locus diversity in a British population of the self-incompatible (SI) coloniser
      Senecio squalidus (Oxford Ragwort). Despite the predicted constraints to mating
      imposed by such a low number of S alleles, S. squalidus maintains a strong
      sporophytic self-incompatibility (SSI) system and there is no evidence for a
      breakdown of SSI or any obvious negative reproductive consequences for this
      highly successful coloniser. The present paper assesses mating behaviour in an
      Oxford S. squalidus population through observations of its effect on spatial
      patterns of genetic diversity and thus the extent to which it is responsible for
      ameliorating the potentially detrimental reproductive consequences of low S
      allele diversity in British S. squalidus. A spatial autocorrelation (SA)
      treatment of S locus and allozyme polymorphism data for four loci indicates that
      mating events regularly occur at all the distance classes examined from 60 to 480
      m throughout the entire sample population. Less SA is observed for S locus data
      than for allozyme data in accordance with the hypothesis that SSI and low
      diversity at the S locus are driving these large-scale mating events. The limited
      population structure at small distances of 60 m and less observed for SA analysis
      of the Me-2 locus and by F-statistics for all the allozyme data, is evidence of
      some local relatedness due to limited seed and pollen dispersal in S. squalidus.
      However, the overall impression of mating dynamics in this S. squalidus
      population is that of ample potential mating opportunities with many individuals
      at large population scales, indicating that reproductive success is not seriously
      affected by few S alleles available for mating interactions.

PMID- 14576745
TI  - Genetic diversity of nuclear and mitochondrial genomes in Pinus parviflora Sieb.
      & Zucc. (Pinaceae) populations.
AB  - Genetic diversities of the nuclear and mitochondrial genomes in Pinus parviflora
      were studied in 16 populations, which were distributed across most of the
      species' range in Japan. Six mitochondrial DNA haplotypes were identified among
      the 16 populations. The intrapopulation diversity of allozymes was similar to
      that of other endemic woody species (H(S)=0.259). Although P. parviflora is
      distributed in discrete populations, differentiation between these was very low
      (G(ST)=0.044). In addition, the extent of genetic differentiation between two
      varieties (var. pentaphylla and var. parviflora) was extremely low (G(VT)=0.001).
      Intrapopulation diversity of mitochondrial DNA was also very low (H(S)=0.098),
      but population differentiation was high (G(ST)=0.863). Moreover, the distribution
      of haplotypes reflected the taxonomic differences between P. parviflora var.
      pentaphylla and var. parviflora. The populations of var. pentaphylla and var.
      parviflora contained different haplotypes. Differing modes of inheritance may
      account for the differences in nuclear and mitochondrial genetic diversity.

PMID- 14576746
TI  - Genetic differentiation among populations of Sesleria albicans Kit. ex Schultes
      (Poaceae) from ecologically different habitats in central Europe.
AB  - As observed for many other plant species, the populations of Sesleria albicans in
      Central Europe are located in habitats, which differ to a high degree from each
      other with regard to ecological factors such as nutrients, light and water as
      well as in type of land use. The species colonizes limestone cliffs, pavements,
      screes, grazed and mown grasslands, heaths, fens and open woodlands. In this
      study, we used random amplified polymorphic DNA (RAPD) analysis to investigate
      the genetic differentiation among 25 populations of S. albicans from six
      different types of habitat (beech forests, alpine and lowland rocky ridges,
      lowland screes, fens, calcareous grasslands). With RAPD analysis, 344 fragments
      could be amplified, of which 95.9% were polymorphic. The level of polymorphism
      ranged from 29.7 to 56.7% polymorphic bands per population and was correlated
      with population size. In an analysis of molecular variance (AMOVA), used to
      detect variation among individuals within populations, among populations from the
      same habitat and among different habitats, most of the genetic variation was
      found within populations (62.06%) and among populations from the same habitat
      (33.36%). In contrast, only a very low level of differentiation could be observed
      among different habitats (4.58%). The results of our study give only little
      evidence for an ecotypic differentiation of Sesleria albicans. This
      differentiation is principally conceivable, but obviously not related to the
      investigated RAPD loci.

PMID- 14576747
TI  - Yield stability in Coffea canephora from diallel mating designs monitored for 14
      years.
AB  - The genetic parameters of several agronomic traits were estimated in Coffea
      canephora in a triangular diallel with six parents and in a partial diallel with
      18 parents. The yield data came from harvests obtained over 14 years divided into
      an initial 6-year cycle, a second cycle of 5 years after cutting back and a third
      cycle of 3 years after topping. Risk incidence was also observed over several
      years. The general combining abilities (GCA) were the principal sources of
      variation for the various traits considered. Parents derived from the Yangambi
      selections (Democratic Republic of Congo) proved to be best for yields in the
      three cropping cycles. The rank correlations between the GCA of the various
      traits indicated that first-cycle production was still not enough to predict the
      GCA for yield over 14 years. Susceptibility to leaf anthracnose and to drought
      could lead to modifications in successive classifications, with a more
      significant impact on production during the first cycle. The differences in
      susceptibility to Coffee Berry Borers had an impact on yield, which increased in
      line with coffee tree age. There was a rather good relation between inherent
      values and values in parent combinations and it was thus possible to choose
      parents on their own performance.

PMID- 14576748
TI  - The role and potential of sialic acid in human nutrition.
AB  - Sialic acids are a family of nine-carbon acidic monosaccharides that occur
      naturally at the end of sugar chains attached to the surfaces of cells and
      soluble proteins. In the human body, the highest concentration of sialic acid (as
      N-acetylneuraminic acid) occurs in the brain where it participates as an integral
      part of ganglioside structure in synaptogenesis and neural transmission. Human
      milk also contains a high concentration of sialic acid attached to the terminal
      end of free oligosaccharides, but its metabolic fate and biological role are
      currently unknown. An important question is whether the sialic acid in human milk
      is a conditional nutrient and confers developmental advantages on breast-fed
      infants compared to those fed infant formula. In this review, we critically
      discuss the current state of knowledge of the biology and role of sialic acid in
      human milk and nervous tissue, and the link between sialic acid, breastfeeding
      and learning behaviour.

PMID- 14576749
TI  - Precision of the doubly labeled water method in a large-scale application:
      evaluation of a streamlined-dosing protocol in the Observing Protein and Energy
      Nutrition (OPEN) study.
AB  - OBJECTIVE: To evaluate whether the doubly labeled water (DLW) method is precise
      under conditions required for a large-scale evaluation of dietary intake
      instruments. DESIGN: Energy expenditure was measured in 484 subjects (main
      study). Subjects received one of five different weight DLW dose bottles prepared
      in advance of the study. A repeat energy expenditure measure was obtained in a
      subset of 24 subjects (substudy). DLW measures of energy expenditure were
      performed over a 2-week interval with urine collection at the beginning and end.
      SETTING: Free-living environment with three clinic visits in the Maryland
      suburban area of Washington, DC. SUBJECTS: A total of 484 subjects (261 men and
      223 women) aged 40-69 y, 24 of whom (13 men and 11 women) participated in a
      substudy in which DLW was administered a second time. RESULTS: The coefficient of
      variation of the DLW energy expenditure measurement was 5.1%. This included a
      2.9% analytical and a 4.2% physiologic variation. Based on observed initial
      isotopic enrichment, the preweighed dosages were optimal in 70% of the main study
      subjects, and 9% received a dose that was less than optimal. Only six subjects
      (1%) were excluded because the final isotopic enrichment was too low to conduct
      precise measurement. CONCLUSIONS: Use of preweighed DLW dosages did not
      compromise the precision of the DLW method. The DLW method is a reliable measure
      of energy expenditure for large-scale evaluations of dietary intake instruments.

PMID- 14576750
TI  - Tracing the Mediterranean diet through principal components and cluster analyses
      in the Greek population.
AB  - OBJECTIVE: To identify dietary patterns, and their socio-demographic and
      lifestyle correlates in a large sample of Greek adults, and assess their
      adherence to the traditional Mediterranean diet. DESIGN: Principal component (PC)
      analysis was used to identify dietary patterns among 28 034 participants of the
      Greek branch of the European Prospective Investigation into Cancer and Nutrition.
      Dietary information was collected through a validated, semiquantitative, food
      frequency questionnaire. The extracted PCs were subsequently regressed on
      sociodemographic and lifestyle variables. Analyses were also performed to
      classify individuals with similar dietary behavior into clusters. RESULTS: Four
      PCs were identified: PC1 resembled the Mediterranean diet, PC2 approximated a
      vegetarian diet with emphasis on seed oils, PC3 reflected a preference for
      sweets, and PC4 reflected a Western diet. PC1 and PC2 were positively associated
      with age, education, physical activity, and nonsmoking status. Females, in
      comparison to males, scored higher on PC1 but lower on PC2. Males, younger, more
      educated individuals, nonsmokers and residents of Greater Athens (Attica) scored
      higher on PC3. PC4 was associated with younger age, less education, and current
      smoking. In cluster analyses, cluster A contrasted clusters B and C in having
      much higher mean PC1- and PC2-scores and substantially lower PC3- and PC4-scores.
      PC1 and PC4 were, respectively, positively and inversely correlated with an a
      priori Mediterranean-diet score; PC2 and PC3 were unrelated to it. CONCLUSION:
      The Mediterranean-like PC1-score as well as the vegetarian-like PC2 were higher
      among older, more educated people, and were associated with a healthier lifestyle
      than PC4, which reflected a Western-type diet. PC1 was strongly positively
      associated with an a priori Mediterranean-diet score.

PMID- 14576751
TI  - Lifestyle factors associated with glycaemic control and body mass index in older
      adults with diabetes.
AB  - OBJECTIVE: To investigate the relations between lifestyle factors (diet and
      exercise), glycated haemoglobin (HbA(1c)) and body mass index (BMI) in older
      adults with diabetes. DESIGN AND SETTING: A community hospital-based cross
      sectional study of 150 noninstitutionalized, ambulatory adults (>/=65 y) with
      diabetes, residing within New Zealand's Kapiti region. SUBJECTS: Patients were
      recruited from all general practices; two diabetes clinics; local diabetes
      society and through advertisements in community newspapers. A total of 211
      eligible people were identified, but 60 refused to participate and one withdrew.
      In all, 150 people completed the study (71% participation rate). METHODS:
      Nutrient intakes were calculated by a food-frequency questionnaire. Physical
      activity was assessed by interview using a validated questionnaire. Medical
      history and demographic data were obtained by interview or self-completed
      questionnaires; height, weight and HbA(1c) were measured. Multivariate models
      using bootstrapping and stepwise linear regression were used to select factors
      associated with HbA(1c) and BMI. RESULTS: Each five-unit increase in energy from
      dietary saturated fat and five-unit increase in BMI were associated with 6% (95%
      confidence interval=2-10%; P=0.004) and 4% (0.3-7%; P=0.031) increases in
      HbA(1c), respectively. For females with moderate, compared with low overall
      activity, there was a 14% (7-20%; P=0.000) reduction in BMI while for males the
      reduction was only 5% (-1-11%; P=0.116). BMI decreased 5% (2-9%; P=0.004) with
      each 10-y increase in age, while a five-unit increment in energy from dietary
      sucrose was associated with a 6% (1-11%; P=0.025) increase in BMI. CONCLUSIONS:
      Reducing dietary saturated fat and excess body weight may be useful means of
      improving glycaemic control in older adults with diabetes. Increasing physical
      activity and reducing energy from dietary sucrose may assist weight control, the
      former particularly in women.

PMID- 14576752
TI  - Estimation of body fatness from body mass index and bioelectrical impedance:
      comparison of New Zealand European, Maori and Pacific Island children.
AB  - OBJECTIVE: To compare percentage body fat (%BF) for a given body mass index (BMI)
      among New Zealand European, Maori and Pacific Island children. To develop
      prediction equations based on bioimpedance measurements for the estimation of fat
      free mass (FFM) appropriate to children in these three ethnic groups. DESIGN:
      Cross-sectional study. Purposive sampling of schoolchildren aimed at recruiting
      three children of each sex and ethnicity for each year of age. Double cross
      validation of FFM prediction equations developed by multiple regression. SETTING:
      Local schools in Auckland. SUBJECTS: Healthy European, Maori and Pacific Island
      children (n=172, 83 M, 89 F, mean age 9.4+/-2.8(s.d.), range 5-14 y).
      MEASUREMENTS: Height, weight, age, sex and ethnicity were recorded. FFM was
      derived from measurements of total body water by deuterium dilution and
      resistance and reactance were measured by bioimpedance analysis. RESULTS: For
      fixed BMI, the Maori and Pacific Island girls averaged 3.7% lower %BF than
      European girls. For boys a similar relation was not found since BMI did not
      significantly influence %BF of European boys (P=0.18). Based on bioimpedance
      measurements a single prediction equation was developed for all children: FFM
      (kg)=0.622 height (cm)(2)/resistance+0.234 weight (kg)+1.166, R(2)=0.96,
      s.e.e.=2.44 kg. Ethnicity, age and sex were not significant predictors.
      CONCLUSIONS: A robust equation for estimation of FFM in New Zealand European,
      Maori and Pacific Island children in the 5-14 y age range that is more suitable
      than BMI for the determination of body fatness in field studies has been
      developed.

PMID- 14576753
TI  - Estimates of percentage body fat in young adolescents: a comparison of dual
      energy X-ray absorptiometry and air displacement plethysmography.
AB  - OBJECTIVE: To evaluate the accuracy of percentage body fat (%fat) estimates from
      air displacement plethysmography (ADP) against an increasingly recognised
      criterion method, dual-energy X-ray absorptiometry (DXA), in young adolescents.
      DESIGN: Cross-sectional evaluation. SETTING: Leeds General Infirmary, Centre for
      Bone and Body Composition Research, Leeds, UK. SUBJECTS: In all, 28 adolescents
      (12 males and 16 females), age (mean+/-s.d.) 14.9+/-0.5 y, body mass index 21.2+/
      2.9 kg/m(2) and body fat (DXA) 24.2+/-10.2% were assessed. RESULTS: ADP estimates
      of %fat were highly correlated with those of DXA in both male and female subjects
      (r=0.84-0.95, all P<0.001; s.e.e.=3.42-3.89%). Mean %fat estimated by ADP using
      the Siri (1961) equation (ADP(Siri)) produced a nonsignificant overestimation in
      males (0.67%), and a nonsignificant underestimation in females (1.26%). Mean %fat
      estimated by ADP using the Lohman (1986) equations (ADP(Loh)) produced a
      nonsignificant underestimation in males (0.90%) and a significant underestimation
      in females (3.29%; P<0.01). Agreement between ADP and DXA methods was examined
      using the total error (TE) and methods of Bland and Altman (1986). Males produced
      a smaller TE (ADP(Siri) 3.28%; ADP(Loh) 3.49%) than females (ADP(Siri) 3.81%;
      ADP(Loh) 4.98%). The 95% limits of agreement were relatively similar for all %fat
      estimates, ranging from +/-6.57 to +/-7.58%. Residual plot analyses, of the
      individual differences between ADP and DXA, revealed a significant bias
      associated with increased %fat (DXA), only in girls (P<0.01). CONCLUSIONS: We
      conclude that ADP, at present, has unacceptably high limits of agreement compared
      to a criterion DXA measure. The ease of use, suitability for various populations
      and cost of ADP warrant further investigation of this method to establish
      biological variables that may influence the validity of body fat estimates.

PMID- 14576754
TI  - Folic acid supplement decreases the homocysteine increasing effect of filtered
      coffee. A randomised placebo-controlled study.
AB  - OBJECTIVE: Elevated levels of plasma total homocysteine (tHcy) are identified as
      independent risk factors for coronary heart disease and for fetal neural tube
      defects. tHcy levels are negatively associated with folic acid, pyridoxine and
      cobalamine, and positively associated with coffee consumption and smoking. A
      total of 600 ml of filtered coffee results in a tHcy increase that 200 mug of
      folic acid or 40 mg of pyridoxine supplementation might eliminate. DESIGN:
      Randomised, blinded study with two consecutive trial periods. SETTING: Free
      living population. Volunteers. SUBJECTS: A total of 121 healthy, nonsmoking men
      and women (78%) aged 29-65 y. INTERVENTIONS: (1) A coffee-free period of 3 weeks,
      (2) 600 ml coffee/day and a supplement of 200 mug folic acid/day or placebo for 4
      weeks, (3) 3-week coffee-free period, (4) 600 ml coffee/day and 40 mg
      pyridoxine/day or placebo for 4 weeks. MAIN OUTCOME MEASURES: The difference
      between the change in tHcy in the supplement group and the change in tHcy in the
      placebo group during the 4-week trial period. RESULTS: Coffee abstention resulted
      in a tHcy decrease of 1.04 mumol/l for the whole group. In the subsequent coffee
      period, a further decrease of 0.17 mumol/l was observed in the folic acid group
      whereas an increase of 1.26 mumol/l was observed in the placebo group, the
      difference was 1.43 mumol/l (95% CI: 0.80, 2.07). Pyridoxine supplement had no
      impact on tHcy levels. CONCLUSIONS: Supplementation of 200 mug folic acid/day
      eliminates the tHcy increasing effect of 600 ml filtered coffee in subjects not
      already on folic acid supplements. A supplement of 40 mg pyridoxine/day does not
      have the same effect.

PMID- 14576755
TI  - Childhood and adult dietary vitamin E intake and cardiovascular risk factors in
      mid-life in the 1946 British Birth Cohort.
AB  - OBJECTIVES: To determine whether dietary vitamin E intake in childhood or mid
      life was predictive of adult hypertension and high waist circumference, as two
      important risk factors for cardiovascular disease. DESIGN: Longitudinal study of
      a social class stratified random sample of all the legitimate, singleton births
      in the week of 3-9 March 1946. SETTINGS: England, Scotland and Wales. SUBJECTS:
      The 2980 survey members who provided information on diet, health and
      sociodemographic information at two time points; age 4 y in 1950 (24-h dietary
      recall) and 43 y in 1989 (48-h dietary recall). MAIN OUTCOME MEASURES: Outcomes
      were adjusted odds ratios (ORs) for hypertension and high waist circumference at
      age 43 y by thirds of vitamin E intake, relative to the highest intake thirds at
      both ages. RESULTS: The lowest consumers of vitamin E in both childhood and
      adulthood were more likely to be hypertensive (OR 1.8, 95% confidence interval
      (CI): 1.03-3.08) and have high waist circumference (OR 1.6, 95% CI: 1.02-2.43)
      than those consuming high levels at both ages. A low intake of vitamin E at just
      one time point was not associated with a statistically significant increased risk
      of hypertension or high waist circumference. Social class was also an independent
      and equally strong predictor of these coronary risk factors, indicating that the
      relation between social class and cardiovascular risks was not mediated solely by
      the current measures of diet and lifestyle. CONCLUSIONS: Unique data on vitamin E
      intake from foods in both childhood and adulthood have indicated that relatively
      low intake of vitamin E at both ages predicted hypertension and high waist
      circumference at age 43 y.

PMID- 14576756
TI  - Reduction of plasma homocysteine and serum methylmalonate concentrations in
      apparently healthy elderly subjects after treatment with folic acid, vitamin B12
      and vitamin B6: a randomised trial.
AB  - OBJECTIVES: To investigate, in an elderly population: (1) the effects of oral B
      vitamin therapy on P-tHcys, S-MMA and Hb/MCV, (2) the appropriate decision limit
      for 'high' metabolite concentrations and (3) the estimated prevalence of vitamin
      B(12)/folate deficiency on the basis of different decision limits. DESIGN: Double
      blind placebo-controlled intervention study. SETTING: Outpatient clinic.
      SUBJECTS: A total of 209 community-dwelling subjects, median age 76 y (range 70
      93) y. INTERVENTION: Four months of oral daily supplementation with 0.5 mg
      cyanocobalamin, 0.8 mg folic acid and 3 mg vitamin B(6). RESULTS: High P- tHcys
      was found in 64% of men and 45% of women, high S-MMA in 11% of both. Vitamin
      B(12) deficiency was observed in 7.2% and folate deficiency in 11% of all
      subjects. Health-related upper reference limits for the metabolites at the start
      were higher than the laboratory's upper reference limits. The latter were,
      however, similar to those of the vitamin replete group. There was a significant
      decrease in P-tHcys (P<0.001) and S-MMA (P=0.009) after 4 months of vitamin
      treatment. In a multivariate analysis, the P-Hcys change correlated positively
      with baseline P-tHcys and inversely with baseline P-folate and transferrin
      saturation (Fe/TIBC ratio). The S-MMA change correlated with baseline S-MMA and
      inversely with baseline vitamin B(12) and age. CONCLUSIONS: Suboptimal vitamin
      status is an important cause of elevated P-tHcys and S-MMA in apparently healthy
      elderly subjects. Oral B-vitamin therapy is an effective and convenient way to
      normalise P-tHcys and S-MMA.

PMID- 14576757
TI  - Food consumed does not account for the higher prevalence of obesity among stunted
      adults in a very-low-income population in the Northeast of Brazil (Maceio,
      Alagoas).
AB  - OBJECTIVE: To study the food pattern of stunted and nonstunted, obese and
      nonobese individuals in a very-low-income population. DESIGN: A household survey.
      SETTING: Slum set up by the 'Homeless Movement', city of Maceio (Alagoas),
      Brazil. SUBJECTS AND METHODS: A total of 532 adults classified by sex, stature
      (Z</= and Z > -2s.d. of the NCHS curves), and body mass index (BMI) were compared
      using the following variables: waist circumference, waist-hip circumference ratio
      (W/H), percentage body fat (skinfold thickness and bioelectrical impedance), and
      food intake (24-h recall). RESULTS: The prevalence of stunting was 22.6%. In all,
      30% of the stunted subjects were overweight or obese, compared with 23% for the
      nonstunted individuals (P<0.05). In women, logistic regression analysis showed a
      strong association among weight, abdominal fat, and stunting (r=0.81). No
      significant differences were observed in the values of W/H or in the qualitative
      menu of the different categories. Energy intake was below the RDA figures (about
      63%). There was similarity among the groups regarding the proportion of
      macronutrients, except for the fact that stunted obese women ingested less fat
      and protein than nonstunted obese women. Stunted obese individuals consumed less
      energy (5962 kJ) than the population as a whole (6213 kJ), an amount far lower
      than their average needs, which were calculated on the basis of their shorter
      stature (8109 kJ). CONCLUSION: The observed energy consumption seems compatible
      with the panorama of undernutrition present in the population, but it does not
      explain the high prevalence of obesity detected.

PMID- 14576758
TI  - Individual saturated fatty acids and nonfatal acute myocardial infarction in
      Costa Rica.
AB  - BACKGROUND: Epidemiological studies on the effect of individual saturated fatty
      acids (SFAs) on cardiovascular disease, especially in developing countries with
      different dietary patterns, are scarce. OBJECTIVE: To determine the risk of
      nonfatal acute myocardial infarction (MI) associated with consumption of
      individual SFAs and their food sources in Costa Rica. DESIGN: The cases (n=485)
      were survivors of a first acute MI and were matched by age, sex and area of
      residence to population controls (n=508). Data on anthropometrical measurements,
      lifestyle and diet were collected using interviewer-administered questionnaires.
      RESULTS: In analyses adjusted for confounders, consumption of total and
      individual SFAs was associated with an increased risk of MI. The odds ratio (OR)
      (95% confidence intervals) for 1% increase in energy from total saturated fat was
      1.12 (1.03-1.21) while it was 1.51 (1.03-2.22) for lauric acid+myristic acid,
      1.14 (1.01-1.30) for palmitic acid and 2.00 (1.34-3.00) for stearic acid.
      Although lauric and myristic acids were associated with increased risk of MI,
      they were consumed in small amounts and most of the saturated fat (87%) came from
      palmitic and stearic acids, which derived mainly from red meat and fried foods.
      Consumption of cheese (1-2 vs 0 servings/day) was associated with increased risk
      of MI (OR=3.07; 95% confidence interval: 1.74-5.39; P for trend <0.0001), while
      consumption of low-fat milk was not. CONCLUSION: Increased consumption of total
      and individual SFAs is associated with increased risk of MI. Lauric, myristic and
      stearic acids were more potent than palmitic acid.

PMID- 14576759
TI  - Salivary cortisol and heart rate in stunted and nonstunted Nepalese school
      children.
AB  - OBJECTIVE: To test the hypothesis that stunted Nepalese children have an altered
      stress response system when compared with matched nonstunted children in response
      to a battery of psychological tests. DESIGN: Case-control study. SETTING: Poor
      urban areas of Kathmandu, Nepal. SUBJECTS: A total of 64 stunted (less than -2
      s.d. height-for-age) children compared with 64 nonstunted (> -1s.d. height-for
      age) schoolchildren between 8 and 10 y old matched for school and sex. METHODS: A
      psychological test session was administered, which included mental arithmetic and
      two tests of working memory. Salivary cortisol samples were obtained at five
      points during testing, and heart rate was measured during testing and also at
      baseline. Salivary cortisol samples were also obtained once early in the morning.
      Hemoglobin was assessed at the testing session, and extensive data were obtained
      on the social background of the children's families. RESULTS: Stunted Nepalese
      children showed a blunted physiologic response (salivary cortisol and heart rate)
      to psychological stressors (P<0.05) when compared with nonstunted children, but
      were not different from the nonstunted children in baseline measures, when
      controlling for social background. The two groups were not different in terms of
      social background. CONCLUSIONS: These findings suggest that childhood growth
      retardation may be associated with changes in physiological arousal, and that
      stunting could be associated with hyporesponsivity in response to psychological
      stress.

PMID- 14576760
TI  - Earlier smoking habits are associated with higher serum lipids and lower milk fat
      and polyunsaturated fatty acid content in the first 6 months of lactation.
AB  - OBJECTIVE: To investigate the relation between maternal smoking habits, plasma
      lipids and milk fatty acid (FA) content and composition. DESIGN: Breastfeeding
      mothers who gave birth to healthy, full-term infants were recruited. Mothers were
      interviewed on smoking habits, being defined smokers (S) when usually smoking at
      least five cigarettes per day before pregnancy. SETTING: Department of
      Pediatrics, San Paolo Hospital, Milan, Italy. SUBJECTS: In total, 92 mothers: 61
      non-S (NS) and 31 S. INTERVENTIONS: Pooled hindmilk was collected at the first
      raise of milk (colostrum stage), 1, 3 and 6 months, and total lipid (TL) content
      and fatty acid (FA) composition were evaluated. Maternal dietary habits were
      assessed by a food-frequency questionnaire. Two subsamples (16 NS, 6 S) were
      investigated after delivery and at 3 months for serum lipids and FA status. At 6
      months after delivery, the number of mothers still breastfeeding decreased to 30.
      Variables were compared using nonparametric tests. RESULTS: In smoking mothers
      serum levels of triglycerides, cholesterol and low-density lipoproteins were
      higher, while those of high-density lipoproteins were lower. TL content in breast
      milk was similar in the two groups just after delivery but higher in milk from NS
      at 1 month. TL content and FA absolute amounts of linoleic, arachidonic, alpha
      linolenic and docosahexaenoic (DHA) acid in breast milk were lower in S vs NS 1
      month after delivery. Also 3 months after delivery, the breast milk of smoking
      mothers contained less DHA than the breast milk of nonsmoking mothers.
      CONCLUSIONS: Maternal cigarette smoking in early pregnancy is associated with
      higher plasma lipid levels and lower milk TL and DHA content in the first months
      of lactation.

PMID- 14576761
TI  - Influence of renal function on spontaneous dietary intake and on nutritional
      status of chronic renal insufficiency patients.
AB  - OBJECTIVE: To analyze the spontaneous food intake and the nutritional parameters
      of patients with different degrees of chronic renal insufficiency (CRI) at the
      onset of predialysis treatment. DESIGN: Cross-sectional. SETTING: Outpatient
      Clinic of the Nephrology Division of Federal University of Sao Paulo, Brazil.
      SUBJECTS: The analysis involved 487 (187 women and 300 men) patients with
      moderate to advanced CRI who were evaluated in the first visit to the clinic.
      RESULTS: Patients were divided according to creatinine clearance (CrCl)
      quartiles. CrCl in the first quartile was lower than 19.9 ml/min/1.73 m(2) and in
      the fourth one was higher than 43 ml/min/1.73 m(2). Energy intake was
      significantly (P<0.05) lower in the first quartile when compared with the fourth
      one while protein intake estimated by protein equivalent of nitrogen appearance
      (PNA) was significantly lower in the first, second and third quartiles in
      comparison with the fourth (P<0.05). Body mass index (BMI) and percentage of
      ideal body weight were significantly decreased in the three lowest levels of
      renal function. Standard per cent of triceps skinfold thickness was lower in the
      first quartile when compared with the fourth one. Compared with the fourth
      quartile, standard per cent of midarm muscle circumference (MAMC) was lower in
      the second and in the third quartile. CrCl correlated directly and significantly
      with PNA (r=0.30; P<0.01), energy intake (r=0.17; P<0.01), and MAMC (r=0.20;
      P<0.01). In a multiple linear regression analysis, controlling for energy and
      protein intake, CrCl correlated significantly and positively with BMI and MAMC.
      CONCLUSION: This study suggests that a spontaneous decrease in energy and protein
      intake as well as in anthropometric indices follows a decline in renal function
      in patients with no previous dietary intervention.

PMID- 14576762
TI  - Birth weight, growth and feeding in infancy: relation to serum lipid
      concentration in 12-month-old infants.
AB  - OBJECTIVE: To assess the effects of birth size, growth and feeding in infancy on
      serum lipids in 12-month-old infants. DESIGN: A longitudinal observation study on
      infants' consumption and growth. Food and growth records were made every month.
      At 6, 9 and 12 months, food records were weighed to calculate intake. Serum total
      cholesterol (TC), high-density lipoprotein-cholesterol (HDL), low-density
      lipoprotein (LDL) -cholesterol and triglyceride concentrations were analysed at
      12 months. SETTINGS: Birth and growth information was gathered from maternity
      wards and healthcare centres in Iceland and food consumption data at home.
      SUBJECTS: Randomly selected newborns (n=180) according to the mother's domicile
      and 77% (n=138) participated, of them 75% (n=103), came in for blood sampling.
      RESULTS: Among boys, a 1 kg higher birth weight resulted in a 0.79 mmol/l higher
      TC (P=0.005), but nonsignificant after adjustment for growth. Duration of
      breastfeeding was related to LDL-cholesterol (B=0.06 +/-0.02, P=0.020, adj.
      R(2)=0.039), adjusting for gender. Independent of size at birth and
      breastfeeding, increase in length from 6 to 12 months and in weight from birth to
      12 months were negatively related to TC (B=-0.455+/-0.156, P=0.008 and B=-1.086+/
      0.474, P=0.032, respecitvely) in boys. PUFA was the strongest nutrient variable
      predicting TC (B=0.332, adj. R(2)=0.24, P>0.001). Cod liver oil consumption
      increased both TC and LDL-cholesterol in girls (B=0.141+/-0.051, P=0.008 and
      B=0.112+/-0.047, P=0.021, respectively). CONCLUSION: Slower growth of high birth
      weight infants and breastfeeding contributes to higher TC concentration at the
      age of 12 months. Nutrient intake in infancy also affects lipid profile. The
      effect of birth weight, growth and nutrient intake in infancy on lipid profile is
      different for boys and girls.

PMID- 14576763
TI  - Starch fermentation by faecal bacteria of infants, toddlers and adults:
      importance for energy salvage.
AB  - OBJECTIVE: Little is known of the degree to which the colon salvages energy
      through starch fermentation in young children. Using a simulated colonic
      environment, we aimed to account for the fate of fermented raw and cooked starch
      in two groups of young children and in adults. DESIGN: A slurry was prepared from
      faecal samples from six infants (7-10 months), six toddlers (16-21 months) and
      seven adults (24-56 y). Each slurry was anaerobically incubated with raw or
      cooked maize starch in MacCartney bottles in a shaking water bath. Parallel
      incubations were stopped at 4 and 24 h. The headspace gas volume was analysed for
      CO(2) and methane. The culture supernatant was analysed for short-chain fatty
      acids (SCFA), lactate and residual starch. RESULTS: Different patterns of
      fermentation were seen at 4 and 24 h. For raw starch, the production of SCFA
      decreased with subject age at 4 h but not at 24 h. With both substrates at 4 h,
      toddler stools produced significantly more CO(2) than infants or adults, but
      there were no statistical differences at 24 h. Methane was detected in three
      adults only. Lactate was detected mainly at 4 h in children. CONCLUSIONS: The
      results suggest that fermentation, particularly of raw starch, is a more rapid
      process in young children than in adults. A highly efficient energy salvage
      process may occur in the colon of young children.

PMID- 14576765
TI  - Short-term repeatability of a food frequency questionnaire in New Zealand
      children aged 1-14 y.
AB  - OBJECTIVE: To evaluate the repeatability of a children's food frequency
      questionnaire (FFQ) by gender, ethnicity, and age group. DESIGN: A 117-item FFQ
      asking about food intake patterns over the past 4 weeks was developed using food
      records from 428 children (204 boys and 224 girls) and the reproducibility on
      average 13 days apart was tested in 130 children (78 boys and 52 girls). Children
      were recruited using clustered probability sampling (n=103), and a convenience
      sample of 25 Maori children. SETTING: Children aged 1-14 y from Auckland,
      Feilding and Shannon, New Zealand. SUBJECTS: There were 71 Maori, 20 Pacific, and
      39 Other children. RESULTS: Spearman correlations between the two FFQs ranged
      from 0.50 for bread to 0.82 for fruit, with a median of 0.76 for spreads and
      nonmilk drinks, and Cronbach's coefficient alpha's ranged from 0.59 for bread to
      0.92 for nonmilk drinks, with a median of 0.85 for mixed meat dishes. There were
      no significant differences between the two administrations, apart from reporting
      higher intakes of vegetables and snacks & sweets in the first FFQ. Correlation
      coefficients tended to be slightly higher in boys than in girls, and in Other
      ethnic groups compared to Maori and Pacific children. Correlations were slightly
      higher for the 1-4 y age group, intermediate in the 10-14 y age group, and lowest
      in the 5-9 y-old age group. CONCLUSIONS: Overall, the FFQ described here shows
      similar or better repeatability in New Zealand children of all major ethnic
      groups compared to other child or adolescent FFQs.

PMID- 14576764
TI  - Dietary pattern and usual nutrient intakes of Peruvian women during pregnancy.
AB  - OBJECTIVE: To describe dietary intakes and nutrient adequacy during pregnancy in
      a sample of Peruvian women. DESIGN: Descriptive, observational prospective study,
      nested within a double-masked, controlled, zinc-supplementation trial during
      pregnancy. SETTING: Hospital Materno-Infantil 'Cesar Lopez Silva', in Villa El
      Salvador, an impoverished shantytown in Lima, Peru. SUBJECTS: A subsample of
      women enrolled in the larger trial. These women all had low-risk singleton
      pregnancies and were receiving prenatal care at the study hospital. A total of
      168 24-h dietary recalls were collected at 10-24 weeks gestation and 120 recalls
      were collected at 28-30 weeks gestation. RESULTS: Median intakes of protein,
      riboflavin, niacin, vitamin C and phosphorus met the current US RDA for
      pregnancy, whereas intakes of thiamin, folate, vitamin A, calcium, iron and zinc
      were well below the recommendations at both time periods. Dietary intake of
      energy (mostly from carbohydrates) showed a significant increase from 10-24 to 28
      30 weeks gestation, as did intakes of folate and vitamin A. The nutrients with
      the highest estimated prevalences of inadequacy at both points in pregnancy were
      iron (93%), zinc (88-80%), folate (87-74%) and calcium (86-82%). CONCLUSION:
      Usual dietary intakes were found to be relatively adequate in terms of their
      energy and protein contents. However, high prevalences of inadequate intakes were
      estimated, particularly for iron, zinc and calcium.

PMID- 14576766
TI  - Serum magnesium level among pregnant women in a rural community of Haryana State,
      India.
AB  - OBJECTIVE: Assessment of serum magnesium levels among pregnant women in a rural
      community. DESIGN: A community-based cross-sectional study. SETTING:
      Investigation was conducted in six villages of a rural block of District
      Faridabad, Haryana State, India. SUBJECTS: In total, 283 pregnant women with
      pregnancy duration of 28 weeks and more were enrolled for the detailed study.
      Blood from the antecubital vein was drawn and serum magnesium levels were
      estimated by the atomic absorption spectrophotometric method. RESULTS: In all,
      44% of the pregnant women had serum levels less than the normal level (1.80
      mg/dl). There was a significant decrease (P=0.01) in serum magnesium levels with
      the increase in parity. CONCLUSION: A high prevalence of magnesium deficiency was
      found among the pregnant women.

PMID- 14576767
TI  - Functional characterization of mitochondria in neutrophils: a role restricted to
      apoptosis.
AB  - Mitochondria are known to combine life-supporting functions with participation in
      apoptosis by controlling caspase activity. Here, we report that in human blood
      neutrophils the mitochondria are different, because they preserve mainly death
      mediating abilities. Neutrophil mitochondria hardly participate in ATP synthesis,
      and have a very low activity of the tested marker enzymes. The presence of
      mitochondria in neutrophils was confirmed by quantification of mitochondrial DNA
      copy number, by detection of mitochondrial porin, and by JC-1 measurement of
      Deltapsi(m). During neutrophilic differentiation, HL-60 cells demonstrated a
      profound cytochrome c depletion and mitochondrial shape change reminiscent of
      neutrophils. However, blood neutrophils containing extremely low amounts of
      cytochrome c displayed strong caspase-9 activation during apoptosis, which was
      also observed in apoptotic neutrophil-derived cytoplasts lacking any detectable
      cytochrome c. We suggest that other proapoptotic factors such as Smac/DIABLO and
      HtrA2/Omi, which are massively released from the mitochondria, have an important
      role in neutrophil apoptosis.

PMID- 14576768
TI  - Cyclin D3 and c-MYC control glucocorticoid-induced cell cycle arrest but not
      apoptosis in lymphoblastic leukemia cells.
AB  - Glucocorticoids (GC) induce cell cycle arrest and apoptosis in lymphoblastic
      leukemia cells. To investigate cell cycle effects of GC in the absence of
      obscuring apoptotic events, we used human CCRF-CEM leukemia cells protected from
      cell death by transgenic bcl-2. GC treatment arrested these cells in the G1 phase
      of the cell cycle due to repression of cyclin D3 and c-myc. Cyclin E and Cdk2
      protein levels remained high, but the kinase complex was inactive due to
      increased levels of bound p27(Kip1). Conditional expression of cyclin D3 and/or c
      myc was sufficient to prevent GC-induced G1 arrest and p27(Kip1) accumulation
      but, importantly, did not interfere with the induction of apoptosis. The combined
      data suggest that repression of both, c-myc and cyclin D3, is necessary to arrest
      human leukemia cells in the G1 phase of the cell division cycle, but that neither
      one is required for GC-induced apoptosis.

PMID- 14576769
TI  - Retinoid-related molecules require caspase 9 for the effective release of Smac
      and the rapid induction of apoptosis.
AB  - Certain retinoid-related molecules (RRMs) with agonist or antagonist activities
      have been described to induce apoptosis in a variety of cancer cell lines and
      show promise for the treatment of cancer. Similar to other chemotherapeutic
      drugs, these retinoid analogs have been suggested to induce apoptosis through the
      intrinsic pathway, which requires the release of cytochrome c from the
      mitochondria for the effective activation of caspase 9. Expression of a
      catalytically inactive form of caspase 9, which functions as a dominant negative
      mutant, inhibits the induction of DEVDase activity and nuclear fragmentation by
      selective RRMs. Whereas the RRMs could induce the release of cytochrome c in the
      absence of caspase 9 activity, the later is necessary for the effective release
      of Smac/Diablo from the mitochondria. Furthermore, overexpression of Bcl-2 or Bcl
      X(L) also inhibits RRM-induced apoptosis. We demonstrate that activation of
      caspase 2 by the agonist MX2870-1 requires caspase 9 activity and is inhibited by
      Bcl-2 overexpression. In contrast, the antagonist MX781 induces cleavage of
      procaspase 2 upstream of mitochondria and independently of caspase 9. Thus, two
      retinoid analogs with unique characteristics activate two distinct apical
      caspases (2 or 9) to initiate apoptosis. In addition to caspase-mediated cell
      death, sustained exposure to the RRMs can also lead to loss of cell viability in
      cells lacking caspase 9 activity or in cells stimulated in the presence of the
      caspase inhibitor Z-VAD-fmk. Moreover, MX2870-1 and MX781 produce cell cycle
      arrest independently of caspase activity and the retinoid receptors.

PMID- 14576770
TI  - VEIDase is a principal caspase-like activity involved in plant programmed cell
      death and essential for embryonic pattern formation.
AB  - Plant embryogenesis is intimately associated with programmed cell death. The
      mechanisms of initiation and control of programmed cell death during plant embryo
      development are not known. Proteolytic activity associated with caspase-like
      proteins is paramount for control of programmed cell death in animals and yeasts.
      Caspase family of proteases has unique strong preference for cleavage of the
      target proteins next to asparagine residue. In this work, we have used synthetic
      peptide substrates containing caspase recognition sites and corresponding
      specific inhibitors to analyse the role of caspase-like activity in the
      regulation of programmed cell death during plant embryogenesis. We demonstrate
      that VEIDase is a principal caspase-like activity implicated in plant
      embryogenesis. This activity increases at the early stages of embryo development
      that coincide with massive cell death during shape remodeling. The VEIDase
      activity exhibits high sensitivity to pH, ionic strength and Zn(2+)
      concentration. Altogether, biochemical assays show that VEIDase plant caspase
      like activity resembles that of both mammalian caspase-6 and yeast metacaspase,
      YCA1. In vivo, VEIDase activity is localised specifically in the embryonic cells
      during both the commitment and in the beginning of the execution phase of
      programmed cell death. Inhibition of VEIDase prevents normal embryo development
      via blocking the embryo-suspensor differentiation. Our data indicate that the
      VEIDase activity is an integral part in the control of plant developmental cell
      death programme, and that this activity is essential for the embryo pattern
      formation.

PMID- 14576771
TI  - Human normal hepatocytes are susceptible to apoptosis signal mediated by both
      TRAIL-R1 and TRAIL-R2.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) triggers
      apoptosis in tumor cells without toxicity to normal cells, but some recombinant
      versions of TRAIL caused hepatocyte death. We generated fully human monoclonal
      antibodies (mAbs) that bind specifically to TRAIL receptor 1 (TRAIL-R1) and TRAIL
      receptor 2 (TRAIL-R2), which mediate apoptosis signal when they ligate with
      TRAIL, to investigate the contribution of each receptor to induce tumor cell
      apoptosis and hepatocyte toxicity. All of mAbs to TRAIL-R1 and TRAIL-R2 induced
      cell death in several cancer cell lines susceptible to TRAIL but not in human
      umbilical vein endothelial cells in vitro. Both anti-TRAIL-R1 mAbs and anti-TRAIL
      R2mAbs also caused cell death in hepatocytes. However, a subset of mAbs to TRAIL
      R2, which was characterized by the TRAIL blocking activity, did not show strong
      hepatocyte toxicity. These results indicate that human normal hepatocytes are
      susceptible to both TRAIL-R1- and TRAIL-R2-mediated apoptosis signal. Cell Death
      and Differentiation (2004) 11, 203-207. doi:10.1038/sj.cdd.4401331 Published
      online 24 October 2003

PMID- 14576772
TI  - Negative regulatory effect of an oligodendrocytic bHLH factor OLIG2 on the
      astrocytic differentiation pathway.
AB  - In the developing vertebrate nervous system, multipotent neural stem cells
      produce both neurons and glia. OLIG2 is a basic helix-loop-helix transcription
      factor that plays critical roles in oligodendrocyte and motor neuron development;
      however, its role in astrocytic development remains elusive. In this study, we
      analyzed an effect of OLIG2 on cytokine-induced astrocytic differentiation from
      mouse telencephalic neuroepithelial cells. We show that the presence of OLIG2
      protein leads to inhibition of the promoter activation of astrocyte-specific
      glial fibrillary acidic protein gene. We found that OLIG2 abolishes complex
      formation between a transcriptional coactivator p300 and a transcription factor,
      signal transducer and activator of transcription 3 (STAT3), which is activated by
      astrocytic differentiation-inducing cytokines, such as leukemia inhibitory factor
      (LIF). The enforced expression of OLIG2 in neuroepithelial cells inhibits the LIF
      induced astrocytic differentiation. We also show that the OLIG2 protein in the
      nuclei of neural precursor cells disappears in accordance with astrocytic
      differentiation during culture with LIF. Together, these results reveal a novel
      molecular function of OLIG2 on the astrocyte development. Cell Death and
      Differentiation (2004) 11, 196-202. doi:10.1038/sj.cdd.4401332 Published online
      24 October 2003

PMID- 14576773
TI  - Restoration of sensitivity to anoikis in Ras-transformed rat intestinal
      epithelial cells by a Ras inhibitor.

PMID- 14576774
TI  - Exacerbated inflammatory responses in transgenic mice expressing an inhibitor of
      apoptosis protein (OpIAP).
AB  - Members of the inhibitor of apoptosis protein family are involved not only in
      suppressing apoptosis, but also in signal transduction, cell division, and are
      associated with some types of cancers. Here we show that transgenic expression of
      the inhibitor of apoptosis protein OpIAP in murine T lymphocytes leads to a
      significant increase in T-cell receptor-induced cell activation, proliferation
      and cytokine production. Transgenic T lymphocytes expressing OpIAP have a lower
      proliferation threshold in response to T-cell receptor stimulation. Unstimulated
      OpIAP transgenic T lymphocytes show elevated nuclear levels of NF-kappaB
      transcription factor that increase after in vivo antigen peptide treatment. OpIAP
      transgenic animals present an exacerbated inflammatory response in an
      experimental contact hypersensitivity model, suggesting increased T-cell
      activation in vivo. These data indicate a new role for the inhibitor of apoptosis
      proteins in T-lymphocyte activation and proliferation.

PMID- 14576775
TI  - Substrate cleavage by caspases generates protein fragments with Smac/Diablo-like
      activities.
AB  - Smac/Diablo and HtrA2/Omi promote apoptosis by binding to and antagonizing IAP
      proteins, including the 'X chromosome-linked inhibitor of apoptosis' (XIAP). Here
      we show that caspase-mediated proteolysis of a limited subset of cell death
      substrates exposes functional Smac/Diablo-like N-termini after cleavage, which
      are able to bind to and antagonize XIAP. We propose that this mechanism may
      establish a feedforward sensitization of the apoptotic pathway and contribute to
      the functional redundancy of IAP antagonism. In addition, this may be
      particularly relevant in Alzheimer's disease since the caspase-generated C31
      peptide, an established cytotoxin, acquires Smac/Diablo-like properties after
      apoptotic processing.

PMID- 14576776
TI  - Caspase-dependent and -independent T-cell death pathways in pathogenic simian
      immunodeficiency virus infection: relationship to disease progression.
AB  - Studies of human immunodeficiency virus (HIV) and nonhuman primate models of
      pathogenic and nonpathogenic simian immunodeficiency virus (SIV) infections have
      suggested that enhanced ex vivo CD4 T-cell death is a feature of pathogenic
      infection in vivo. However, the relative contributions of the extrinsic and
      intrinsic pathways to programmed T-cell death in SIV infection have not been
      studied. We report here that the spontaneous death rate of CD4+ T cells from
      pathogenic SIVmac251-infected rhesus macaques ex vivo is correlated with CD4 T
      cell depletion and plasma viral load in vivo. CD4+ T cells from SIVmac251
      infected macaques showed upregulation of the death ligand (CD95L) and of the
      proapoptotic proteins Bim and Bak, but not of Bax. Both CD4+ and CD8+ T cells
      from SIVmac251-infected macaques underwent caspase-dependent death following CD95
      ligation. The spontaneous death of CD4+ and CD8+ T cells was not prevented by a
      decoy CD95 receptor or by a broad-spectrum caspase inhibitor (zVAD-fmk),
      suggesting that this form of cell death is independent of CD95/CD95L interaction
      and caspase activation. IL-2 and IL-15 prevented the spontaneous death of CD4+
      and CD8+ T cells, whereas IL-10 prevented only CD8 T-cell death and IL-7 had no
      effect on T-cell death. Our results indicate that caspase-dependent and caspase
      independent pathways are involved in the death of T cells in pathogenic SIVmac251
      infected primates.

PMID- 14576777
TI  - Cathepsin D mediates cytochrome c release and caspase activation in human
      fibroblast apoptosis induced by staurosporine.
AB  - There is increasing evidence that proteases other than caspases, for example, the
      lysosomal cathepsins B, D and L, are involved in apoptotic cell death. In the
      present study, we present data that suggest a role for cathepsin D in
      staurosporine-induced apoptosis in human foreskin fibroblasts. Cathepsin D and
      cytochrome c were detected partially released to the cytosol after exposure to
      0.1 muM staurosporine for 1 h. After 4 h, activation of caspase-9 and -3 was
      initiated and later caspase-8 activation and a decrease in full-length Bid were
      detected. Pretreatment of cells with the cathepsin D inhibitor, pepstatin A,
      prevented cytochrome c release and caspase activation, and delayed cell death.
      These results imply that cytosolic cathepsin D is a key mediator in staurosporine
      induced apoptosis. Analysis of the relative sequence of apoptotic events
      indicates that, in this cell type, cathepsin D acts upstream of cytochrome c
      release and caspase activation.

PMID- 14576784
TI  - FDI president outlines goals.

PMID- 14576778
TI  - Nothing changes... or does it?

PMID- 14576789
TI  - Alphabet soup--why do we need so many postgraduate qualifications?

PMID- 14576790
TI  - Orthodontics. Part 1: Who needs orthodontics?

PMID- 14576791
TI  - Dental management considerations for the patient with an acquired coagulopathy.
      Part 1: Coagulopathies from systemic disease.

PMID- 14576798
TI  - Parental attitudes to the care of the carious primary dentition.
AB  - OBJECTIVES: To examine parents' attitudes to the dental care of their children,
      taking into account the family's socio-economic background, dentally-related
      behaviour including the child's level of dental anxiety and dental treatment
      history. METHODS: A cross sectional study of all 5-year-old children living in
      Ellesmere Port and Chester. All children were clinically examined; dmft and its
      components were recorded. A postal questionnaire was sent to the children's
      parents to measure their preferences for dental care with reference to two
      scenarios, (1) if their child had a carious but asymptomatic primary tooth, or
      (2) if their child had a carious primary tooth which was causing toothache.
      Parents were also asked to provide information on the dental attendance pattern
      of their child and an assessment of their child's dental anxiety. Family socio
      economic status was recorded using the Townsend material deprivation index of the
      electoral ward in which they resided. RESULTS: Questionnaires were distributed to
      the home addresses of the 1,745 children who were clinically examined, and 1,437
      were returned, giving a response rate of 82%. In both scenarios the majority of
      parents were happy to leave the decision on treatment to the dentist. In the
      asymptomatic tooth scenario, approximately one third of parents wanted the tooth
      to remain untreated but periodically monitored, only 6% expressed a desire to
      have their child's tooth restored. Multivariate analysis showed that parents of
      children who had a filling (OR 4.32 95%CI 2.21-8.43) or extraction (OR 2.24 95%CI
      1.11-4.53) in the past were significantly more likely to want restorative care
      for their children. In the scenario where the child had toothache, multivariate
      analysis confirmed that parents had a preference for an intervention (extraction
      or filling) if they lived in a deprived area (Townsend score OR 1.10, 95% CI
      1.04, 1.16) or if their child had had an extraction (OR 4.35, 95% CI 1.59, 11.88)
      or filling (OR 2.39, 95% CI 1.05, 5.45) in the past, after controlling for
      gender, attendance and parentally reported anxiety. When preference for an
      extraction was considered as the dependent variable, there was no significant
      relationship with past restorative treatment. In both scenarios there was no
      association between parentally reported anxiety of the child and parental
      preferences for treatment. CONCLUSIONS: In this part of the UK, there was little
      explicit support amongst parents for the restoration of asymptomatic carious
      primary teeth. Parental expectations for the dental care of young children with
      caries in their primary teeth, were closely related to the treatment experiences
      of the child. Families living in deprived areas expressed a preference for more
      interventionist care than their more affluent counterparts. Parentally judged
      anxiety of the child or their past dental attendance behaviour had no association
      with parents' preferences for the care of their children.

PMID- 14576799
TI  - Access to NHS dentistry in South Cheshire: a follow up of people using telephone
      helplines to obtain NHS dental care.
AB  - OBJECTIVE: To follow up calls made to NHS Direct and South Cheshire Dental
      Helpline concerning getting access to an NHS dentist in South Cheshire. DESIGN:
      Contact details of callers who had consented to a follow up call were passed by
      helpline staff to a researcher at regular intervals. In a structured interview,
      callers were asked why they had telephoned the helpline and whether they had
      subsequently obtained NHS dental care. Follow up calls continued until a total of
      200 replies had been gathered, either by telephone or post (for those where
      telephone contact could not be made). Follow up calls were made between September
      2001 and March 2002. RESULTS: During the study period only three callers from
      South Cheshire contacted NHS Direct with a dental access query and consented to a
      follow up call, compared with 219 callers to South Cheshire Dental Helpline. Only
      10% were not contacted either by telephone or post. A comparison with figures for
      calls made to South Cheshire Dental Helpline between April 2000 and March 2001
      suggests that during the study period a year later the access problem has
      improved. However, there were still a few areas in South Cheshire where
      significant numbers of dental access queries were being received. Twenty five per
      cent of unregistered and 22% of registered callers still felt that they had
      problems getting access to NHS dental care after using information from the
      helplines. CONCLUSION: A small but significant number of people in South Cheshire
      have problems accessing NHS dental care.

PMID- 14576800
TI  - Developing teaching and learning innovations in dental training: the example of
      the Progress File Learning System.

PMID- 14576813
TI  - Focus Awards 2003.

PMID- 14576816
TI  - Oncogenes, tumor suppressors and p52 NF-kappaB.
AB  - A role for the p52 NF-kappaB subunit in tumorigenesis has been steadily emerging
      since its discovery as a gene associated with chromosomal translocations in B-
      and T-cell lymphomas. Now Eliopoulos and co-workers have extended these studies
      to examine the effect of the Epstein-Barr virus (EBV)-encoded latent infection
      membrane protein 1 (LMP1) on p52. They find that LMP1 stimulates the processing
      of p100 to p52 NF-kappaB. Moreover, nuclear p52 is also associated with LMP1
      expression in tumor tissue biopsies. They also demonstrate that the pathway
      leading to p100/p52 processing is distinct from that engaged by LMP1 to activate
      other NF-kappaB subunits through IkappaBalpha degradation. A clearer picture is
      now developing of the important role that p52 NF-kappaB plays during normal cell
      growth and how subverting its function can contribute to oncogenesis.

PMID- 14576817
TI  - Epstein-Barr virus-encoded latent infection membrane protein 1 regulates the
      processing of p100 NF-kappaB2 to p52 via an IKKgamma/NEMO-independent signalling
      pathway.
AB  - The oncogenic Epstein-Barr virus (EBV)-encoded latent infection membrane protein
      1 (LMP1) constitutively activates the 'canonical' NF-kappaB pathway that involves
      the phosphorylation and degradation of IkappaBalpha downstream of the IkappaB
      kinases (IKKs). In this study, we show that LMP1 also promotes the proteasome
      mediated proteolysis of p100 NF-kappaB2 resulting in the generation of active
      p52, which translocates to the nucleus in complex with the p65 and RelB NF-kappaB
      subunits. LMP1-induced NF-kappaB transactivation is reduced in nf-kb2(-/-) mouse
      embryo fibroblasts, suggesting that p100 processing contributes to LMP1-mediated
      NF-kappaB transcriptional effects. This pathway is likely to operate in vivo, as
      the expression of LMP1 in primary EBV-positive Hodgkin's lymphoma and
      nasopharyngeal carcinoma biopsies correlates with the nuclear accumulation of
      p52. Interestingly, while the ability of LMP1 to activate the canonical NF-kappaB
      pathway is impaired in cells lacking IKKgamma/NEMO, the regulatory subunit of the
      IKK complex, p100 processing remains unaffected. As a result, nuclear
      translocation of p52, but not p65, occurs in the absence of IKKgamma. These data
      point to the existence of a novel signalling pathway that regulates NF-kappaB in
      LMP1-expressing cells, and may thereby play a role in both oncogenic
      transformation and the establishment of persistent EBV infection.

PMID- 14576818
TI  - Regulation of the gene encoding glutathione S-transferase M1 (GSTM1) by the Myb
      oncoprotein.
AB  - The identification of Myb 'target' genes will not only aid in the understanding
      of how overexpression of Myb, or expression of activated forms of Myb, leads to
      cellular transformation but will also shed light on its role in normal cells.
      Using a combination of an estrogen-regulated Myb-transformed cell line (ERMYB)
      and PCR-based subtractive hybridization, we have identified the gene (GSTM1)
      encoding the detoxification enzyme glutathione S-transferase M1 as being
      transcriptionally upregulated by Myb. Functional analysis of the GSTM1 promoter
      using reporter assays indicated that both the DNA binding and transactivation
      domains of Myb were required for transcriptional activation. Mutational ana-lysis
      of consensus Myb-binding sites (MBS) in the promoter and electrophoretic mobility
      gel shift analysis indicated that one of the three potential MBS can bind Myb
      protein, and is the primary site involved in the regulation of this promoter by
      Myb.

PMID- 14576819
TI  - Critical role of cyclin D3 in TSH-dependent growth of thyrocytes and in
      hyperproliferative diseases of the thyroid gland.
AB  - We report that cyclin D3 is rate limiting for G1 progression in thyroid
      follicular cells and that its constitutive upregulation by chronic stimulation of
      the TSH/cAMP pathway plays a role in human and experimental hyperproliferative
      diseases of the thyroid gland. These conclusions are supported by in vitro and in
      vivo studies. In rat thyrocytes (PC Cl 3 cells), cyclin D3 expression is enhanced
      in response to activation of the TSH/cAMP pathway. Interference with the
      expression of G1 cyclins (in particular cyclin D3) by the antisense methodology
      strongly reduced TSH-dependent proliferation of PC Cl 3 cells, indicating that
      proper progression through G1 requires cyclin D3. Accordingly, PC Cl 3 cells
      engineered to overexpress cyclin D3 (PC-D3 cells) show enhanced growth rate and
      elude hormone-dependence and contact inhibition. Using an animal experimental
      model of thyroid stimulation, we demonstrate that cyclin D3 is a key mediator of
      TSH-dependent proliferation of thyroid follicular cells also in vivo. Cyclin D3
      protein levels were higher in the thyrocytes from glands of propylthiouracil
      treated rats compared with control animals. The increase in cyclin D3 expression
      occurred after the propylthiouracil-induced increase in TSH levels and preceded
      the burst of cell proliferation. Finally, we found that cyclin D3 protein is
      expressed in a fraction of human goiters but it is strongly overexpressed in most
      follicular adenomas.

PMID- 14576820
TI  - Overexpression of mammalian Rad51 does not stimulate tumorigenesis while a
      dominant-negative Rad51 affects centrosome fragmentation, ploidy and stimulates
      tumorigenesis, in p53-defective CHO cells.
AB  - Rad51 protein plays a pivotal role in homologous recombination (HR), which is
      involved in double-strand break repair and in genome maintenance. Despite
      interactions with tumor suppressor proteins, the role of mammalian Rad51 and more
      generally of HR in tumor prevention is not clearly established. Indeed, both high
      and low frequencies of HR as well as high and low levels of RAD51 expression have
      been reported in tumors and in precancerous conditions. To address the question
      of the impact of HR on tumorigenesis, we used Chinese hamster ovary (CHO) p53
      defective cell lines overexpressing the mouse MmRAD51, which stimulates HR (we
      name these lines: Hyper-rec lines). In parallel, we used CHO cell lines
      expressing a RAD51 dominant-negative form that specifically inhibits gene
      conversion without affecting cell viability (Hypo-rec lines). These different
      lines were injected into nude mice to measure their tumorigenicity. Hypo-rec
      lines generated a higher frequency of tumors, which also exhibited faster growth,
      compared to control and Hyper-rec lines. Consistent with tumorigenicity, Hypo-rec
      cells exhibit spontaneous centrosome duplication defects and aneuploidy. These
      results are the first direct evidence of involvement of RAD51 in tumor
      repression.

PMID- 14576821
TI  - Breast cancer-specific gene 1 interacts with the mitotic checkpoint kinase BubR1.
AB  - The abnormal expression of breast cancer-specific gene 1 (BCSG1) in malignant
      mammary epithelial cells is highly associated with the development and
      progression of breast cancer. A series of in vitro and in vivo studies performed
      in our laboratory and others have demonstrated that BCSG1 expression
      significantly stimulates proliferation, invasion, and metastasis of breast cancer
      cells. However, currently little is known about how BCSG1 exerts its oncogenic
      functions. To elucidate the cellular mechanisms underlying the effects of BCSG1
      in breast cancer cells, we used a yeast two-hybrid system to screen for proteins
      that could associate with BCSG1. Through this screening, we identified the
      mitotic checkpoint protein BubR1 as a novel binding partner of BCSG1. The
      specific association of BCSG1 with BubR1 in breast cancer cells was demonstrated
      by immunoprecipitation and GST pull-down assays. Intriguingly, experiments
      conducted in four different cell lines all showed that exogenous expressions of
      BCSG1 consistently reduce the cellular levels of the BubR1 protein without
      affecting BubR1 mRNA expression. The tendency of endogenous BCSG1 expression
      coinciding with lower BubR1 protein levels was also observed in seven out of
      eight breast cancer cell lines. We further showed that the reducing effect of
      BCSG1 on BubR1 protein expression could be prevented by treating BCSG1
      transfected cells with MG-132, a selective 26S proteasome inhibitor, implying
      that the proteasome machinery may be involved in the BCSG1-induced reduction of
      the BubR1 protein. Accompanied with a reduction of BubR1 protein level, BCSG1
      expression resulted in multinucleation of breast cancer cells upon treatment with
      spindle inhibitor nocodazole, indicating an impaired mitotic checkpoint. Taken
      together, our novel findings suggest that BCSG1 may accelerate the progression of
      breast cancer at least in part by compromising the mitotic checkpoint control
      through inactivation of BubR1.

PMID- 14576822
TI  - Expression of estrogen receptor beta isoforms in normal breast epithelial cells
      and breast cancer: regulation by methylation.
AB  - Two novel estrogen receptor beta (ERbeta) mRNA isoforms that diverge in their 5'
      untranslated regions, ERbeta mRNA (0K-1) and ERbeta mRNA (0N-1), have recently
      been identified. This indicates that transcription of the human ERbeta gene
      occurs from at least two different promoters, named promoter 0K and promoter 0N.
      The aim of this study was to investigate the expression of ERbeta isoforms in
      primary cultures of normal breast epithelial cells, a panel of breast cancer cell
      lines and in normal breast and breast cancer tissues; and to examine whether
      methylation of the two ERbeta promoters is involved in regulation of ERbeta gene
      expression. Using quantitative real-time PCR techniques, we found that ERbeta
      mRNA levels were significantly lower in breast cancer cell lines than in primary
      cultures of normal breast epithelial cells. Bisulfite genomic sequencing analysis
      revealed that two promoters of the ERbeta gene exhibit distinct methylation
      patterns. Promoter 0N was unmethylated in normal breast epithelial cells, but
      extensively methylated in breast cancer cell lines. In contrast, promoter 0K was
      unmethylated in both normal and malignant breast epithelial cells. We
      demonstrated a significant correlation between promoter 0N hypermethylation and
      loss of ERbeta mRNA expression in breast cancer cell lines. Treatment of breast
      cancer cells with demethylating agent effectively reactivated the expression of
      ERbeta mRNA. The observations from the cell lines were also reflected in primary
      breast cancer tumors. Thus, expression of ERbeta mRNA in breast tumors was found
      to be inversely associated with the degree of methylation of promoter 0N. Our
      results suggest that a decreased level of ERbeta mRNA may be associated with
      breast tumorigenesis, and that DNA methylation is an important mechanism for
      ERbeta gene silencing in breast cancer.

PMID- 14576823
TI  - Positive and negative regulation of deltaN-p63 promoter activity by p53 and
      deltaN-p63-alpha contributes to differential regulation of p53 target genes.
AB  - Mammary epithelial regeneration implies the existence of cellular progenitors
      with retained replicative capacity, prolonged lifespan and developmental potency.
      Evidence exists that deltaN-p63 isoforms preserve these features by modulating
      p53 activity in basal epithelia. deltaN-p63 mRNA levels decline at the onset of
      differentiation suggesting that its transcriptional regulation may contribute to
      the initiation of differentiation. To study transcriptional regulation of deltaN
      p63, a 10.3 kbp fragment containing the deltaN-p63 promoter was isolated. We
      report here that deltaN-p63 is a positive and negative transcriptional target of
      p53 and deltaN-p63-alpha, respectively. Disruption of p53 activity or expression
      abolishes the expression of deltaN-p63-alpha. This regulation is mediated by a
      p53-binding element sufficient to confer these activities to a heterologous
      promoter. Chromatin immune-precipitation indicates that, in asynchronously
      growing cells, p53 occupies this element. In response to DNA damage, deltaN-p63
      alpha is recruited to this element as transcription of deltaN-p63 declines.
      Disruption of deltaN-p63-alpha expression had differential effects on the
      transcriptional regulation of several p53-target genes. These findings indicate
      that p53 contributes to the preservation of basal epithelia by driving the
      expression of deltaN-p63 isoforms. These studies also suggest that in response to
      genotoxic stress, deltaN-p63-alpha mediates the silencing of its own promoter
      thereby altering the pattern of p53-target gene expression.

PMID- 14576824
TI  - Inhibition of Akt kinase signalling and activation of Forkhead are indispensable
      for upregulation of FasL expression in apoptosis of glioma cells.
AB  - Activation of Akt signalling pathway is frequently found in glioma cells and may
      contribute to their resistance to undergo apoptosis in response to conventional
      therapies. We found that cyclosporin A (CsA) induces apoptosis of C6 glioma
      cells, which is associated with transcriptional activation of fasL. In the
      present paper, we investigated an involvement of Akt signalling in the regulation
      of FasL expression in CsA-induced apoptosis. We demonstrated that the level of
      active Akt decreases significantly after CsA treatment, which results in the
      decrease of Forkhead phosphorylation and its translocation to the nucleus. It
      correlated with an increase of binding to the Forkhead-responsive element FHRE
      from the FasL promoter, as demonstrated by gel-shift assays. Although treatment
      with LY294002, a specific inhibitor of PI3 K, decreased the phosphorylation of
      Akt and increased Fkhr translocation to the nucleus, these events were not
      sufficient to induce FasL expression and apoptosis of C6 glioma cells.
      Interference with Akt/Forkhead signalling by membrane-targeted Akt or removal of
      the FKHR-binding sites from the FasL promoter significantly abolished its
      activation. These results indicate that downregulation of Akt signalling and
      activation of Forkhead is a prerequisite for the induction of FasL promoter. It
      may be clinically important for pharmacological intervention in gliomas.

PMID- 14576825
TI  - Gene expression profile by blocking the SYT-SSX fusion gene in synovial sarcoma
      cells. Identification of XRCC4 as a putative SYT-SSX target gene.
AB  - Increasing evidence suggests that the SYT-SSX fusion gene plays an important role
      in synovial sarcoma development and progression. However, very little is known
      about the downstream targets of SYT-SSX. In this study, we used antisense
      oligonucleotides to block the expression of the SYT-SSX fusion gene in synovial
      sarcoma cells. By comparing SYT-SSX inhibited cells with noninhibited cells, the
      gene expression profile was analysed using cDNA microarray and established by
      real-time PCR. Herewith, using a filter containing 1176 cancer-relevant genes, we
      found that the DNA repair gene XRCC4 and the DNA mismatch repair gene MSH2 were
      downregulated, whereas the gene encoding for the serine/threonine protein kinase
      PRK (also known as CNK), and the macrophage inhibitory cytokine MICI (also known
      as PLAB) were upregulated after the inhibition of SYT-SSX. In comparison,
      expression of the XRCC4 gene was undergoing the strongest alteration.
      Consistently, the protein expression of XRCC4 was found to be decreased after SYT
      SSX inhibition, whereas there were no detectable changes for the other gene
      products. Our study provides some clues to elucidate the signaling pathways of
      the SYT-SSX fusion gene, as well as it demonstrates a valuable model system for
      search for other SYT-SSX targets.

PMID- 14576826
TI  - Distinct recruitment of E2F family members to specific E2F-binding sites mediates
      activation and repression of the E2F1 promoter.
AB  - The activity of E2F transcription factors plays a crucial role in mammalian cell
      cycle progression and is controlled by physical association with the pocket
      proteins (pRb and its related p107 and p130). The E2F1 promoter, which contains
      two overlapping E2F-binding sites, is activated at the G1/S transition in an E2F
      dependent manner. Mutational experiments have shown that the distal E2F-binding
      site on the E2F1 promoter is required for transcriptional repression in the G0
      phase, whereas the proximal E2F-binding site contributes to transcriptional
      activation at the G1/S boundary. Consistent with these results, chromatin
      immunoprecipitation assays have revealed that the E2F4/p130 repressor complex
      specifically binds to the distal E2F-binding site, whereas E2F1 and E2F3
      activators preferentially bind to the proximal E2F-binding site. The assays also
      showed that the specific binding of E2F4/p130 complex to the distal site was
      dramatically impaired by a mutation introduced into the contiguous repression
      site (cell Cycle gene Homology Region; CHR). Taken together, these findings
      indicate that the two E2F-binding sites play distinct roles in the regulation of
      E2F1 transcription by interacting with different sets of E2F members and
      cooperating with the contiguous repressor element.

PMID- 14576827
TI  - Single cell tracking reveals that Msh2 is a key component of an early-acting DNA
      damage-activated G2 checkpoint.
AB  - Dysfunction of cell-cycle checkpoints in DNA mismatch repair (MMR)-deficient
      cells in response to DNA damage has implications for anticancer therapy and
      genetic instability. We have studied the cell-cycle effects of MMR deficiency
      (Msh2(-/-)) in primary mouse embryonic fibroblasts (MEFs) exposed to cisplatin
      (10 microM x 1 h) using time-lapse microscopy. Kinetic responses of MEFs from
      different embryos and passage ages varied, but we report a consistent drug
      induced inhibition of mitotic entry (approx. 50%). There was a loss of an early
      acting (<5 h) delay in G2 to M transition in Msh2(-/-) cells, although a later
      acting G2 arrest was apparently normal. This suggests that Msh2 primarily acts to
      delay mitotic entry of cells already in G2, that is, DNA damage incurred during
      G2 does not influence the cell once committed to mitotic traverse. Irrespective
      of Msh2 status, cisplatin treatment and the incurred DNA damage did not effect
      mitotic traverse or show any evidence for early (within 24 h) cell death. The
      results indicate that Msh2(-/-) status can result in the premature commitment to
      mitosis of a cell subpopulation, determined by the fraction residing in G2 at the
      time of damage induction. The findings suggest a new route to MMR-driven genetic
      instability that does not rely primarily on the integrity of the late-acting
      checkpoint.

PMID- 14576828
TI  - Dual-specificity phosphatase Pyst2-L is constitutively highly expressed in
      myeloid leukemia and other malignant cells.
AB  - Northern blotting confirmed previous results indicating that the mitogen
      activated protein kinase (MAPK) phosphatase Pyst2-L was highly expressed in
      leukocytes obtained from acute myeloid leukemia (AML) patients. High levels of
      Pyst2-L mRNA were expressed in bone marrow (BM) and peripheral leukocytes from
      nine AML and acute lymphoblastic leukemia (ALL) patients. BM from healthy
      individuals expressed very low levels of Pyst2-L. Whereas high levels of Pyst2-L
      mRNA and protein were detected in several leukemia cell lines, Pyst2-L mRNA was
      detected neither in 33/34 samples of normal peripheral blood mononuclear cells
      (PBMC) nor in leukocyte fractions enriched with CD34+ cells. Certain solid tumor
      and lymphoblastoid cell lines expressed high levels of Pyst2-L mRNA. In view of
      the association of Pyst2-L to MAPK signaling cascades, we tested if cell
      activation, a process involving MAPK signaling, influences Pyst2-L expression.
      Indeed, activation of T cells and endothelial cells increased Pyst2-L in these
      cells. Furthermore, TPA, a known MAPK activator, induces the expression of both
      Pyst2-L mRNA as well as the Pyst2-L protein in leukemia cells. This induction was
      partially inhibited by PD098059, an Mek1/2-specific inhibitor. Based on the
      results of this and previous studies, we hypothesize that the high levels of
      Pyst2-L detected in the active state of AML and ALL diseases and in other types
      of cancer reflect an altered MAPK signaling pathway in such malignant processes.
      This alteration may be the result of a failed attempt to counter the constitutive
      activation of MAPK in transformed cells or alternatively, may represent the
      activated state of such cells.

PMID- 14576829
TI  - Transient expression of E1A and Ras oncogenes causes downregulation of c-fos gene
      transcription in nontransformed REF52 cells.
AB  - Stable transformation of rat embryo fibroblast (REF) cells with E1A and cHa-ras
      oncogenes leads to downmodulation of c-fos gene transcription. This repression is
      provided in part by the association of Elk-1 transcription factor with histone
      deacetylases mediated through effects of Ras on MAP-kinase cascades. Here, we
      focus on the primary effects of E1A and Ras displayed in transient transfection
      assay on the transactivating capability of Elk-1, which is a key transcription
      factor of c-fos gene regulation. Our data show that E1A is able to suppress serum
      and Ras-induced stimulation of Gal-luc reporter activity by a full-length Gal
      Elk1-428 fusion protein as well as the expression of c-fos promoter-driven
      luciferase constructs (fos-luc). The repression can be relieved by trichostatin
      A, a histone deacetylase (HDAC) inhibitor, implying the involvement of HDACs and
      an inactive chromatin structure formed due to underacetylation of nucleosomal
      histones. Thus, upon transient transfection of E1A and Ras oncogenes in REF52
      cells or their stable expression in E1A+cHa-ras cells, E1A contributes to the
      formation of inactive chromatin structure through association with p300/CBP
      histone acetyltransferases at c-fos promoters, whereas Ras mediates its effect
      through constitutive activation of the MAP/ERK kinase cascade, thereby promoting
      the recruitment of HDAC1 to the Elk-1 transcription factor. As a result,
      downregulation of c-fos gene transcription revealed in established E1A+Ras
      transformants is unlikely to be a consequence of cell transformation itself, but
      follows from primary effects of E1A and Ras on chromatin remodeling factors.

PMID- 14576830
TI  - Transfection of K-rasAsp12 cDNA markedly elevates IL-1beta- and
      lipopolysaccharide-mediated inducible nitric oxide synthase expression in rat
      intestinal epithelial cells.
AB  - Activating mutations of K-ras are frequent in colon tumors and aberrant crypt
      foci, and may play important roles in colon carcinogenesis. Here, we investigated
      the effects of a K-ras codon 12 mutation on inducible nitric oxide synthase
      (iNOS) expression. When rat intestinal epithelial cells (IEC-6) were transfected
      with K-rasAsp12 cDNA, the iNOS expression linked to interleukin-1beta (IL-1beta)
      or lipopolysaccharide (LPS) treatment was markedly increased and prolonged. In
      contrast, it was only very faint and transient in cells transfected with the
      control vector or K-rasWT. Electrophoretic mobility-shift assays demonstrated
      that NF-kappaB binding activity induced by IL-1beta or LPS was also increased in
      K-rasAsp12-transfected cells, along with the binding of CREB-1, CREM-1, ATF-1,
      ATF-2, and Jun D to a cAMP-responsive element (CRE)-like site and the binding of
      C/EBPbeta to a C/EBP-binding consensus site. Furthermore, the anchorage
      independent growth of K-rasAsp12-transfected cells was markedly increased by IL
      1beta or LPS treatment, and decreased by ONO-1714, an iNOS inhibitor. In
      addition, tumor growth in nude mice injected with K-rasAsp12-transfected cells
      was significantly suppressed by NOS inhibition with 50 p.p.m. ONO-1714 or 100
      p.p.m. L-NG-nitroarginine methyl ester. These results suggest that an activating
      mutation of K-ras can markedly enhance the iNOS expression mediated by IL-1beta
      or LPS, through the activation of promoters on NF-kappaB, C/EBP, and CRE-like
      sites, and that nitric oxide contributes to the colony formation and tumor growth
      of K-ras-transformed cells.

PMID- 14576831
TI  - Type-2A protein phosphatase activity is required to maintain death receptor
      responsiveness.
AB  - Type-2A protein phosphatase (PP2A) is a key regulator in many different cell
      signaling pathways and an important determinant in tumorigenesis. One of the
      signaling targets of PP2A is the mitogen-activated protein kinase (MAPK/ERK)
      cascade. In this study, we wanted to determine whether PP2A could be involved in
      regulation of death receptor activity through its capacity to regulate MAPK/ERK.
      To this end, we studied the effects of two different routes of protein
      phosphatase inhibition on death receptor-mediated apoptosis. We demonstrated that
      the apoptosis mediated by Fas, TNF-alpha, and TRAIL in U937 cells is suppressed
      by calyculin A, an inhibitor of type-1 and type-2A protein phosphatases. The
      inhibition of the protein phosphatase activity was shown to subsequently increase
      the MAPK activity in these cells, and the level of activation corresponded to the
      degree of suppression of cytokine-mediated apoptosis. A more physiological
      inhibitor, the intracellular PP2A inhibitor protein I2(PP2A), protected
      transfected HeLa cells in a similar way from Fas-mediated apoptosis and induced
      activation of MAPK in I2(PP2A) transfected cells. A corresponding inhibition
      could also be obtained by stable transfection with a constitutively active form
      of the MAPK kinase, MKK1 (also referred to as MEK1). The inhibitor-mediated
      protection was highly efficient in preventing early stages of apoptosis, as no
      caspase-8 cleavage occurred in these cells. The observed apoptosis suppression is
      likely to facilitate the tumor-promoting effect of a range of different type-2A
      protein phosphatase inhibitors, and could explain the reported tumor association
      of I2(PP2A).

PMID- 14576832
TI  - Comparison of medulloblastoma and normal neural transcriptomes identifies a
      restricted set of activated genes.
AB  - Over 1.4 million transcript tags expressed in 20 different human medulloblastomas
      were counted using serial analysis of gene expression. Digital gene expression
      profiles in the medulloblastoma were compared to multiple regions of the normal
      human brain, revealing 30 transcripts with high expression in multiple tumors and
      little or no expression in the normal cerebellum and other adult and pediatric
      brain regions. Using independent medulloblastoma samples and normal tissue, real
      time PCR verified eight of nine selected genes as candidate tumor-associated
      antigens. Differential protein expression for CD24, prolactin and Topo2A was
      further confirmed by immunohistochemical analysis using medulloblastoma and
      normal brain sections and a tissue microarray. The genes highly expressed in the
      medulloblastoma include PRAME, a cancer-testis antigen and potential targets for
      immunotherapy.

PMID- 14576833
TI  - 12p-amplicon structure analysis in testicular germ cell tumors of adolescents and
      adults by array CGH.
AB  - All invasive testicular germ cell tumors of adolescents and adults (TGCTs), that
      is, seminomas and nonseminomas, show gain of 12p sequences, mostly as
      isochromosomes. Although several candidate genes have been suggested, the
      relevant gene(s) have not been identified yet. About 10% of testicular seminomas,
      however, show a more restricted amplification of the 12p11.2-p12.1 region, in
      which the various amplicons show an apparent overlap, allowing for the shortest
      region of amplification overlap approach, aiming at the identification of
      pathogenetically relevant sequences residing in this region. Here we report on a
      high-resolution 12p-amplicon architecture analysis using microarray-based
      comparative genomic hybridization, the results of which were subsequently
      confirmed by fluorescent in situ hybridization studies. The 12p-specific
      microarray contained 63 positionally selected BAC clones, which are more or less
      evenly distributed over the short arm of chromosome 12 (average spacing: less
      than 500 Kb), including 20 clones within the region of amplification. Out of a
      series of 17 seminomas, seven seminomas showed amplification of the whole
      amplicon region, of which three showed a dip in T/R value in the center of the
      amplified area. A more complex amplification pattern was found in the other 10
      seminomas: three showed predominant amplification at the centromeric border; one
      mainly at the telomeric border; six showed a balanced amplification of both the
      centromeric and telomeric regions. The only nonseminoma investigated showed a
      structure in which the centromeric border was only amplified. These data support
      a mechanistic model in which at least two 12p genes, situated at the border
      regions of the amplicon, are positional candidates capable of actively supporting
      tumor progression in TGCTs.

PMID- 14576834
TI  - Molecular analysis of transitional cell carcinoma using cDNA microarray.
AB  - The incidence of transitional cell carcinoma (TCC), the fourth most common
      neoplasm diagnosed in men, is rising. Despite the development of several
      noninvasive diagnostic tests, none have gained full recognition by the
      clinicians. Gene expression profiling of tumors can identify new molecular
      markers for early diagnosis and disease follow-up. It also allows the
      classification of tumors into subclasses assisting in disease diagnosis and
      prognosis, as well as in treatment selection. In this paper, we employed
      expression profiling for molecular analysis of TCC. A TCC-derived cDNA microarray
      was constructed and hybridized with 19 probes from normal urothelium and TCC
      tissues. Hierarchical clustering analysis identified all normal urothelium
      samples to be tightly clustered and separated from the TCC samples, with 29 of
      the genes significantly induced (t-test, P<10(-5)) in noninvasive TCC compared to
      normal urothelium. The identified genes are involved in epithelial cells'
      functions, tumorigenesis or apoptosis, and could become molecular tools for
      noninvasive TCC diagnosis. Principal components analysis of the noninvasive and
      invasive TCC expression profiles further revealed sets of genes that are
      specifically induced in different tumor subsets, thus providing molecular
      fingerprints that expand the information gained from classical staging and
      grading.

PMID- 14576836
TI  - Introduction to resistance to anticancer agents.

PMID- 14576837
TI  - Cisplatin: mode of cytotoxic action and molecular basis of resistance.
AB  - Cisplatin is one of the most potent antitumor agents known, displaying clinical
      activity against a wide variety of solid tumors. Its cytotoxic mode of action is
      mediated by its interaction with DNA to form DNA adducts, primarily intrastrand
      crosslink adducts, which activate several signal transduction pathways, including
      those involving ATR, p53, p73, and MAPK, and culminate in the activation of
      apoptosis. DNA damage-mediated apoptotic signals, however, can be attenuated, and
      the resistance that ensues is a major limitation of cisplatin-based chemotherapy.
      The mechanisms responsible for cisplatin resistance are several, and contribute
      to the multifactorial nature of the problem. Resistance mechanisms that limit the
      extent of DNA damage include reduced drug uptake, increased drug inactivation,
      and increased DNA adduct repair. Origins of these pharmacologic-based mechanisms,
      however, are at the molecular level. Mechanisms that inhibit propagation of the
      DNA damage signal to the apoptotic machinery include loss of damage recognition,
      overexpression of HER-2/neu, activation of the PI3-K/Akt (also known as PI3
      K/PKB) pathway, loss of p53 function, overexpression of antiapoptotic bcl-2, and
      interference in caspase activation. The molecular signature defining the
      resistant phenotype varies between tumors, and the number of resistance
      mechanisms activated in response to selection pressures dictates the overall
      extent of cisplatin resistance.

PMID- 14576839
TI  - Mechanisms of resistance to topoisomerase I-targeting drugs.
AB  - DNA topoisomerases are a class of enzymes that alter the topology of DNA and are
      targets of several anticancer drugs. Camptothecins (CPTs) are a relatively new
      family of compounds that specifically target topoisomerase I (Top1). These
      compounds "poison" Top1 by binding to the Top1-DNA complex in a manner that
      prevents the religation of DNA. Topotecan and irinotecan are two CPTs that are
      approved for the treatment of a variety of malignancies, including colorectal,
      ovarian, and small cell lung cancers, as well as myeloid malignancies. Although
      CPTs have proven to be effective anticancer drugs, resistance is still a critical
      clinical problem. The mechanisms underlying de novo and acquired clinical
      resistance to CPTs and the newer classes of Top1 poisons are unclear. However,
      based on preclinical studies, it is likely that clinical resistance to these
      drugs is the result of: (1) inadequate accumulation of drug in the tumor, (2)
      resistance-conferring alterations in Top1, or (3) alterations in the cellular
      response to the Top1-CPT interaction. This review will focus on the current
      knowledge regarding mechanisms of resistance to CPTs and other Top1-targeting
      drugs.

PMID- 14576838
TI  - Mechanisms of Taxol resistance related to microtubules.
AB  - Since its approval by the FDA in 1992 for the treatment of ovarian cancer, the
      use of Taxol has dramatically increased. Although treatment with Taxol has led to
      improvement in the duration and quality of life for some cancer patients, the
      majority eventually develop progressive disease after initially responding to
      Taxol treatment. Drug resistance represents a major obstacle to improving the
      overall response and survival of cancer patients. This review focuses on
      mechanisms of Taxol resistance that occur directly at the microtubule, such as
      mutations, tubulin isotype selection and post-translational modifications, and
      also at the level of regulatory proteins. A review of tubulin structure,
      microtubule dynamics, the mechanism of action of Taxol and its binding site on
      the microtubule are included, so that the reader can evaluate Taxol resistance in
      context.

PMID- 14576840
TI  - Retinoids in cancer therapy and chemoprevention: promise meets resistance.
AB  - Retinoids (natural and synthetic derivatives of vitamin A) signal potent
      differentiation and growth-suppressive effects in diverse normal, premalignant,
      and malignant cells. A strong rationale exists for the use of retinoids in cancer
      treatment and chemoprevention based on preclinical, epidemiological, and early
      clinical findings. Despite the success of all-trans-retinoic acid (RA)-based
      differentiation therapy in acute promyelocytic leukemia (APL), the broad promise
      of retinoids in the clinic has not yet been realized. In addition to the expected
      limited activity of any single therapeutic agent, translation of retinoid
      activities from the laboratory to the clinic has met with intrinsic or acquired
      retinoid resistance. Evidence suggests that solid tumors develop intrinsic
      resistance to retinoids during carcinogenesis. In contrast, relapse of APL is
      often associated with acquired resistance to retinoid maturation induction. This
      review discusses what is known about retinoid resistance mechanisms in cancer
      therapy and chemoprevention. Strategies to overcome this resistance will be
      discussed, including combination therapy with other differentiation-inducing,
      cytotoxic or chromatin-remodeling agents, as well as the use of receptor
      selective and nonclassical retinoids. Opportunities exist in the post-genomic era
      to bypass resistance to classical retinoids by identifying target genes and
      associated pathways that directly mediate the antineoplastic effects of
      retinoids. In this regard, the retinoids are useful pharmacological tools to
      reveal important pathways targeted in cancer therapy and chemoprevention.

PMID- 14576841
TI  - Antiestrogen resistance in breast cancer and the role of estrogen receptor
      signaling.
AB  - Antiestrogens include agents such as tamoxifen, toremifene, raloxifene, and
      fulvestrant. Currently, tamoxifen is the only drug approved for use in breast
      cancer chemoprevention, and it remains the treatment of choice for most women
      with hormone receptor positive, invasive breast carcinoma. While antiestrogens
      have been available since the early 1970s, we still do not fully understand their
      mechanisms of action and resistance. Essentially, two forms of antiestrogen
      resistance occur: de novo resistance and acquired resistance. Absence of estrogen
      receptor (ER) expression is the most common de novo resistance mechanism, whereas
      a complete loss of ER expression is not common in acquired resistance.
      Antiestrogen unresponsiveness appears to be the major acquired resistance
      phenotype, with a switch to an antiestrogen-stimulated growth being a minor
      phenotype. Since antiestrogens compete with estrogens for binding to ER, clinical
      response to antiestrogens may be affected by exogenous estrogenic exposures. Such
      exposures include estrogenic hormone replacement therapies and dietary and
      environmental exposures that directly or indirectly increase a tumor's estrogenic
      environment. Whether antiestrogen resistance can be conferred by a switch from
      predominantly ERalpha to ERbeta expression remains unanswered, but predicting
      response to antiestrogen therapy requires only measurement of ERalpha expression.
      The role of altered receptor coactivator or corepressor expression in
      antiestrogen resistance also is unclear, and understanding their roles may be
      confounded by their ubiquitous expression and functional redundancy. We have
      proposed a gene network approach to exploring the mechanistic aspects of
      antiestrogen resistance. Using transcriptome and proteome analyses, we have begun
      to identify candidate genes that comprise one component of a larger, putative
      gene network. These candidate genes include NFkappaB, interferon regulatory
      factor-1, nucleophosmin, and the X-box binding protein-1. The network also may
      involve signaling through ras and MAPK, implicating crosstalk with growth factors
      and cytokines. Ultimately, signaling affects the expression/function of the
      proliferation and/or apoptotic machineries.

PMID- 14576842
TI  - Multidrug resistance mediated by the breast cancer resistance protein BCRP
      (ABCG2).
AB  - Observations of functional adenosine triphosphate (ATP)-dependent drug efflux in
      certain multidrug-resistant cancer cell lines without overexpression of P
      glycoprotein or multidrug resistance protein (MRP) family members suggested the
      existence of another ATP-binding cassette (ABC) transporter capable of causing
      cancer drug resistance. In one such cell line (MCF-7/AdrVp), the overexpression
      of a novel member of the G subfamily of ABC transporters was found. The new
      transporter was termed the breast cancer resistance protein (BCRP), because of
      its identification in MCF-7 human breast carcinoma cells. BCRP is a 655 amino
      acid polypeptide, formally designated as ABCG2. Like all members of the ABC G
      (white) subfamily, BCRP is a half transporter. Transfection and enforced
      overexpression of BCRP in drug-sensitive MCF-7 or MDA-MB-231 cells recapitulates
      the drug-resistance phenotype of MCF-7/AdrVp cells, consistent with current
      evidence suggesting that functional BCRP is a homodimer. BCRP maps to chromosome
      4q22, downstream from a TATA-less promoter. The spectrum of anticancer drugs
      effluxed by BCRP includes mitoxantrone, camptothecin-derived and indolocarbazole
      topoisomerase I inhibitors, methotrexate, flavopiridol, and quinazoline ErbB1
      inhibitors. Transport of anthracyclines is variable and appears to depend on the
      presence of a BCRP mutation at codon 482. Potent and specific inhibitors of BCRP
      are now being developed, opening the door to clinical applications of BCRP
      inhibition. Owing to tissue localization in the placenta, bile canaliculi, colon,
      small bowel, and brain microvessel endothelium, BCRP may play a role in
      protecting the organism from potentially harmful xenobiotics. BCRP expression has
      also been demonstrated in pluripotential "side population" stem cells,
      responsible for the characteristic ability of these cells to exclude Hoechst
      33342 dye, and possibly for the maintenance of the stem cell phenotype. Studies
      are emerging on the role of BCRP expression in drug resistance in clinical
      cancers. More prospective studies are needed, preferably combining BCRP protein
      or mRNA quantification with functional assays, in order to determine the
      contribution of BCRP to drug resistance in human cancers.

PMID- 14576843
TI  - Rituximab (monoclonal anti-CD20 antibody): mechanisms of action and resistance.
AB  - Rituximab, a chimeric monoclonal antibody targeted against the pan-B-cell marker
      CD20, was the first monoclonal antibody to be approved for therapeutic use.
      Treatment with rituximab at standard weekly dosing is effective in more than 50%
      of patients with relapsed or refractory CD20-positive follicular non-Hodgkin's
      lymphoma, but is not curative. It is less effective in other subtypes of CD20
      positive lymphoma and for retreatment, even with CD20 still expressed. Thus,
      binding of rituximab to CD20 is not sufficient to kill many lymphoma cells,
      indicating that there are mechanisms of resistance. Mechanisms of cell
      destruction that have been demonstrated to be activated by rituximab binding to
      CD20 include direct signaling of apoptosis, complement activation and cell
      mediated cytotoxicity. The relative importance of each of these mechanisms in
      determining clinical response to rituximab treatment remains a matter of
      conjecture. Thus, the role of various resistance pathways, some documented in
      experimental systems and others still hypothetical, remains uncertain. Resistance
      could potentially be mediated by alterations in CD20 expression or signaling,
      elevated apoptotic threshold, modulation of complement activity or diminished
      cellular cytotoxicity. As the first of an expanding class of anticancer agents,
      lessons learned regarding the mechanism of rituximab action and resistance will
      be of increasing importance.

PMID- 14576844
TI  - The role of glutathione-S-transferase in anti-cancer drug resistance.
AB  - Glutathione-S-transferases (GSTs) are a family of Phase II detoxification enzymes
      that catalyse the conjugation of glutathione (GSH) to a wide variety of
      endogenous and exogenous electrophilic compounds. GSTs are divided into two
      distinct super-family members: the membrane-bound microsomal and cytosolic family
      members. Microsomal GSTs are structurally distinct from the cytosolic in that
      they homo- and heterotrimerize rather than dimerize to form a single active site.
      Microsomal GSTs play a key role in the endogenous metabolism of leukotrienes and
      prostaglandins. Human cytosolic GSTs are highly polymorphic and can be divided
      into six classes: alpha, mu, omega, pi, theta, and zeta. The pi and mu classes of
      GSTs play a regulatory role in the mitogen-activated protein (MAP) kinase pathway
      that participates in cellular survival and death signals via protein : protein
      interactions with c-Jun N-terminal kinase 1 (JNK1) and ASK1 (apoptosis signal
      regulating kinase). JNK and ASK1 are activated in response to cellular stress.
      GSTs have been implicated in the development of resistance toward chemotherapy
      agents. It is plausible that GSTs serve two distinct roles in the development of
      drug resistance via direct detoxification as well as acting as an inhibitor of
      the MAP kinase pathway. The link between GSTs and the MAP kinase pathway provides
      a rationale as to why in many cases the drugs used to select for resistance are
      neither subject to conjugation with GSH, nor substrates for GSTs. GSTs have
      emerged as a promising therapeutic target because specific isozymes are
      overexpressed in a wide variety of tumors and may play a role in the etiology of
      other diseases, including neurodegenerative diseases, multiple sclerosis, and
      asthma. Some of the therapeutic strategies so far employed are described in this
      review.

PMID- 14576845
TI  - A role for DNA mismatch repair in sensing and responding to fluoropyrimidine
      damage.
AB  - The phenomenon of damage tolerance, whereby cells incur DNA lesions that are
      nonlethal, largely ignored, but highly mutagenic, appears to play a key role in
      carcinogenesis. Typically, these lesions are generated by alkylation of DNA or
      incorporation of base analogues. This tolerance is usually a result of the loss
      of specific DNA repair processes, most often DNA mismatch repair (MMR). The
      availability of genetically matched MMR-deficient and -corrected cell systems
      allows dissection of the consequences of this unrepaired damage in carcinogenesis
      as well as the elucidation of cell cycle checkpoint responses and cell death
      consequences. Recent data indicate that MMR plays an important role in detecting
      damage caused by fluorinated pyrimidines (FPs) and represents a repair system
      that is probably not the primary system for detecting damage caused by these
      agents, but may be an important system for correcting key mutagenic lesions that
      could initiate carcinogenesis. In fact, clinical studies have shown that there is
      no benefit of FP-based adjuvant chemotherapy in colon cancer patients exhibiting
      microsatellite instability, a hallmark of MMR deficiency. MMR-mediated damage
      tolerance and futile cycle repair processes are discussed, as well as possible
      strategies using FPs to exploit these systems for improved anticancer therapy.

PMID- 14576846
TI  - Mechanisms of resistance to STI571 in Philadelphia chromosome-associated
      leukemias.
AB  - Philadelphia chromosome-associated leukemias are among the most well-understood
      human malignancies. The importance of BCR-ABL enzymatic activity in the
      proliferation of the leukemic clone has been confirmed by the high response rates
      of these leukemias to the ABL-selective tyrosine kinase inhibitor STI571, even in
      advanced disease phases, which are characterized by increased genetic
      heterogeneity. Disease relapse has been observed in a subset of patients who had
      initially responded to STI571. Evidence suggests that BCR-ABL activity is
      restored in the majority of these cases of acquired resistance. Molecular studies
      of resistant leukemia cells isolated from patients have implicated BCR-ABL kinase
      domain point mutation as the most common mechanism of resistance. Additionally,
      genomic amplification of the BCR-ABL gene can occasionally be detected. This
      review will highlight mechanisms of STI571 resistance in clinical samples as well
      as preclinical models.

PMID- 14576847
TI  - Role of the tumor microenvironment in mediating de novo resistance to drugs and
      physiological mediators of cell death.
AB  - The emergence of clinical drug resistance continues to be an obstacle for the
      successful treatment of cancer. Our current understanding of mechanisms
      associated with drug resistance has been ascertained by investigating drug
      resistant models created by exposing a parental population to increasing
      concentrations of a cytotoxic. These unicellular drug-resistant models have been
      critical in elucidating drug-resistant mechanism and in some cases have aided in
      the identification of drug targets. However, these models do not address
      resistance mechanisms that contribute to de novo drug resistance. We propose that
      specific niches within the tumor microenvironment may provide a sanctuary for
      subpopulations of tumors cells that affords a survival advantage following
      initial drug exposure and may facilitate the acquisition of acquired drug
      resistance. More specifically, we propose that the bone marrow microenvironment
      is a sanctuary for hema-topoietic cancers. This review will focus on the bone
      marrow microenvironment and its role in conferring resistance to cytotoxics and
      physiological mediators of cell death.

PMID- 14576848
TI  - Drug methylation in cancer therapy: lessons from the TPMT polymorphism.
AB  - The genetic polymorphism of thiopurine methyltransferase (TPMT) is one of the
      most developed examples of pharmacogenetics, spanning from molecular genetics to
      clinical diagnostics for individualizing thiopurine therapy (i.e. azathioprine,
      mercaptopurine, and thioguanine). Elucidation of the molecular mechanisms and
      biochemical consequences of TPMT deficiency demonstrates how pharmacogenetic
      traits can be identified, characterized, and translated to the bedside. Insights
      gained from studies of the TPMT polymorphism illustrate the potential of
      pharmacogenomics to optimize cancer therapy by avoiding toxic side effects in
      genetically distinct subgroups of patients.

PMID- 14576849
TI  - Alterations in the apoptotic machinery and their potential role in anticancer
      drug resistance.
AB  - Anticancer drugs can potentially kill cells in two fundamentally different ways,
      by interfering with cellular processes that are essential for maintenance of
      viability or by triggering an endogenous physiological cell death mechanism.
      Apoptosis is a form of physiological cell death mediated by caspases, a unique
      family of intracellular cysteine proteases. Zymogen forms of these proteases are
      found in virtually all somatic cells, but remain latent until their activation is
      induced by ligation of specific cell surface receptors (the so-called "death
      receptors"), by mitochondrial alterations that allow release of cytochrome c and
      other intermembrane components, or possibly by other mechanisms. Most anticancer
      drugs activate the mitochondrial pathway. This apoptotic pathway is regulated by
      pro- and antiapoptotic members of the Bcl-2 family of proteins. Once activated,
      certain caspases might also be controlled by the inhibitor of apoptosis (IAP)
      proteins. Alterations in apoptotic pathway components or their regulators have
      been detected in a variety of cancers, suggesting that loss of the ability of
      cells to undergo apoptosis might contribute to carcinogenesis. Because cancer
      therapies such as radiation, glucocorticoids, and chemotherapeutic drugs exert
      their beneficial effects, at least in part, by inducing apoptosis of cancer
      cells, the same alterations in apoptotic pathways would be predicted to
      contribute to resistance. A key issue is whether the direct toxic activity of
      these treatments is of benefit when neoplastic cells contain changes that
      diminish their ability to undergo apoptosis.

PMID- 14576850
TI  - Resistance to antifolates.
AB  - The antifolates were the first class of antimetabolites to enter the clinics more
      than 50 years ago. Over the following decades, a full understanding of their
      mechanisms of action and chemotherapeutic potential evolved along with the
      mechanisms by which cells develop resistance to these drugs. These principals
      served as a basis for the subsequent exploration and understanding of the
      mechanisms of resistance to a variety of diverse antineoplastics with different
      cellular targets. This section describes the bases for intrinsic and acquired
      antifolate resistance within the context of the current understanding of the
      mechanisms of actions and cytotoxic determinants of these agents. This
      encompasses impaired drug transport into cells, augmented drug export, impaired
      activation of antifolates through polyglutamylation, augmented hydrolysis of
      antifolate polyglutamates, increased expression and mutation of target enzymes,
      and the augmentation of cellular tetrahydrofolate-cofactor pools in cells. This
      chapter also describes how these insights are being utilized to develop gene
      therapy approaches to protect normal bone marrow progenitor cells as a strategy
      to improve the efficacy of bone marrow transplantation. Finally, clinical studies
      are reviewed that correlate the cellular pharmacology of methotrexate with the
      clinical outcome in children with neoplastic diseases treated with this
      antifolate.

PMID- 14576851
TI  - Vaults: a ribonucleoprotein particle involved in drug resistance?
AB  - Vaults are ribonucleoprotein particles found in the cytoplasm of eucaryotic
      cells. The 13 MDa particles are composed of multiple copies of three proteins: an
      M(r) 100 000 major vault protein (MVP) and two minor vault proteins of M(r) 193
      000 (vault poly-(ADP-ribose) polymerase) and M(r) 240 000 (telomerase-associated
      protein 1), as well as small untranslated RNA molecules of approximately 100
      bases. Although the existence of vaults was first reported in the mid-1980s no
      function has yet been attributed to this organelle. The notion that vaults might
      play a role in drug resistance was suggested by the molecular identification of
      the lung resistance-related (LRP) protein as the human MVP. MVP/LRP was found to
      be overexpressed in many chemoresistant cancer cell lines and primary tumor
      samples of different histogenetic origin. Several, but not all, clinico
      pathological studies showed that MVP expression at diagnosis was an independent
      adverse prognostic factor for response to chemotherapy. The hollow barrel-shaped
      structure of the vault complex and its subcellular localization indicate a
      function in intracellular transport. It was therefore postulated that vaults
      contributed to drug resistance by transporting drugs away from their
      intracellular targets and/or the sequestration of drugs. Here, we review the
      current knowledge on the vault complex and critically discuss the evidence that
      links vaults to drug resistance.

PMID- 14576852
TI  - P-glycoprotein: from genomics to mechanism.
AB  - Resistance to chemically different natural product anti-cancer drugs (multidrug
      resistance, or MDR) results from decreased drug accumulation, resulting from
      expression of one or more ATP-dependent efflux pumps. The first of these to be
      identified was P-glycoprotein (P-gp), the product of the human MDR1 gene,
      localized to chromosome 7q21. P-gp is a member of the large ATP-binding cassette
      (ABC) family of proteins. Although its crystallographic 3-D structure is yet to
      be determined, sequence analysis and comparison to other ABC family members
      suggest a structure consisting of two transmembrane (TM) domains, each with six
      TM segments, and two nucleotide-binding domains. In the epithelial cells of the
      gastrointestinal tract, liver, and kidney, and capillaries of the brain, testes,
      and ovaries, P-gp acts as a barrier to the uptake of xenobiotics, and promotes
      their excretion in the bile and urine. Polymorphisms in the MDR1 gene may affect
      the pharmacokinetics of many commonly used drugs, including anticancer drugs.
      Substrate recognition of many different drugs occurs within the TM domains in
      multiple-overlapping binding sites. We have proposed a model for how ATP
      energizes transfer of substrates from these binding sites on P-gp to the outside
      of the cell, which accounts for the apparent stoichiometry of two ATPs hydrolysed
      per molecule of drug transported. Understanding of the biology, genetics, and
      biochemistry of P-gp promises to improve the treatment of cancer and explain the
      pharmacokinetics of many commonly used drugs.

PMID- 14576853
TI  - The role of p53 in chemosensitivity and radiosensitivity.
AB  - The role of p53 as a central mediator of the DNA damage and other cellular stress
      responses is well established. The ultimate growth-suppressive function of p53 in
      part explains its ability to confer chemosensitivity and radiosensitivity upon
      tumor cells. Recent work in the field has added complexity to our understanding,
      in terms of identifying novel regulators of p53 stability and function,
      elucidation of the importance of the p53 family towards p53 function, a growing
      list of transcriptional targets as well as transcription-independent apoptotic
      effects and mechanisms, tissue specificity of the p53 response, a molecular
      understanding of p53-dependent therapeutic sensitization, and efforts towards
      molecular targeting of the p53 pathway. p53 remains an attractive target for drug
      development in cancer because its alteration provides a fundamental difference
      between normal and cancer cells. Strategies are emerging for the identification
      of mutant p53-specific therapies, therapies targeted at mutant p53-expressing
      tumors, as well as therapies that target various aspects of the p53 life cycle to
      enhance chemosensitization. The tools of molecular imaging are beginning to
      accelerate the pace of discovery and preclinical testing of p53 in animal models.
      The future holds promise for specific, individualized targeting of mutant or wild
      type p53, or its transcriptional targets, in combination therapies with other
      cancer-specific drugs, to maximize tumor cell killing while protecting normal
      cells from toxic side effects.

PMID- 14576854
TI  - Transcriptional regulation of ABC drug transporters.
AB  - P-glycoprotein, the founding member of the ATP-binding cassette (ABC) family of
      drug transporters, was first identified almost three decades ago and shown to
      confer resistance to multiple chemotherapeutic agents when overexpressed in human
      tumors. Subsequent years have witnessed a tremendous effort to characterize the
      function and regulation of P-glycoprotein, initially spurred by the hope that its
      inhibition was the key to overcoming clinical resistance to multiple anticancer
      agents. However, the identification of MRP1, another member of the ABC drug
      transporter family, led to the realization that the multidrug resistance (MDR)
      phenotype is considerably more complex than initially believed. Indeed, at the
      present time at least 10 members of the ABC transporter family have been
      implicated in an MDR phenotype, and it is likely that more will be added to this
      list as studies progress. With this complexity comes the imperative to improve
      our understanding of the function of individual transporters, as well as to
      delineate the mechanisms underlying their expression in normal and tumor cells,
      particularly those that may be amenable to therapeutic intervention. Several
      articles within this volume address the structure and function of drug
      transporters. This review will focus on our current understanding of the
      regulation of ABC drug transporters at the level of transcription.

PMID- 14576855
TI  - Strategies for reversing drug resistance.
AB  - Drug resistance, intrinsic or acquired, is a problem for all chemotherapeutic
      agents. In this review, we examine numerous strategies that have been tested or
      proposed to reverse drug resistance. Included among these strategies are
      approaches targeting the apoptosis pathway. Although the process of apoptosis is
      complex, it provides several potential sites for therapeutic intervention. A
      variety of targets and approaches are being pursued, including the suppression of
      proteins inhibiting apoptosis using antisense oligonucleotides (ASOs), and small
      molecules targeted at proteins that modulate apoptosis. An alternate strategy is
      based on numerous studies that have documented methylation of critical regions in
      the genome in human cancers. Consequently, efforts have been directed at re
      expressing genes, including genes that affect drug sensitivity, using 5
      azacytidine and 2'-deoxy-5-azacytidine (DAC, decitabine) as demethylating agents.
      While this strategy may be effective as a single modality, success will most
      likely be achieved if it is used to modulate gene expression in combination with
      other modalities such as chemotherapy. At a more basic level, attempts have been
      made to modulate glutathione (GSH) levels. Owing to its reactivity and high
      intracellular concentrations, GSH has been implicated in resistance to several
      chemotherapeutic agents. Several approaches designed to deplete intracellular GSH
      levels have been pursued including the use of buthionine-(S,R)-sulfoxime (BSO), a
      potent and specific inhibitor of gamma-glutamyl cysteine synthetase (gamma-GCS),
      the rate-limiting step in the synthesis of GSH, a hammerhead ribozyme against
      gamma-GCS mRNA to downregulate specifically its levels and targeting cJun
      expression to reduce GSH levels. Alternate strategies have targeted p53. The
      frequent occurrence of p53 mutations in human cancer has led to the development
      of numerous approaches to restore wild-type (wt) p53. The goals of these
      interventions are to either revert the malignant phenotype or enhance drug
      sensitivity. The approach most extensively investigated has utilized one of
      several viral vectors. An alternate approach, the use of small molecules to
      restore wt function to mutant p53, remains an option. Finally, the conceptually
      simplest mechanism of resistance is one that reduces intracellular drug
      accumulation. Such reduction can be effected by a variety of drug efflux pumps,
      of which the most widely studied is P-glycoprotein (Pgp). The first strategy
      utilized to inhibit Pgp function relied on the identification of non
      chemotherapeutic agents as competitors. Other approaches have included the use of
      hammerhead ribozymes against the MDR-1 gene and MDR-1-targeted ASOs. Although
      modulation of drug resistance has not yet been proven to be an effective clinical
      tool, we have learned an enormous amount about drug resistance. Should we
      succeed, these pioneering basic and clinical studies will have paved the road for
      future developments.

PMID- 14576856
TI  - Nucleoside anticancer drugs: the role of nucleoside transporters in resistance to
      cancer chemotherapy.
AB  - The clinical efficacy of anticancer nucleoside drugs depends on a complex
      interplay of transporters mediating entry of nucleoside drugs into cells, efflux
      mechanisms that remove drugs from intracellular compartments and cellular
      metabolism to active metabolites. Nucleoside transporters (NTs) are important
      determinants for salvage of preformed nucleosides and mediated uptake of
      antimetabolite nucleoside drugs into target cells. The focus of this review is
      the two families of human nucleoside transporters (hENTs, hCNTs) and their role
      in transport of cytotoxic chemotherapeutic nucleoside drugs. Resistance to
      anticancer nucleoside drugs is a major clinical problem in which NTs have been
      implicated. Single nucleotide polymorphisms (SNPs) in drug transporters may
      contribute to interindividual variation in response to nucleoside drugs. In this
      review, we give an overview of the functional and molecular characteristics of
      human NTs and their potential role in resistance to nucleoside drugs and discuss
      the potential use of genetic polymorphism analyses for NTs to address drug
      resistance.

PMID- 14576857
TI  - The MRP family of drug efflux pumps.
AB  - The MRP family is comprised of nine related ABC transporters that are able to
      transport structurally diverse lipophilic anions and function as drug efflux
      pumps. Investigations of this family have provided insights not only into
      cellular resistance mechanisms associated with natural product chemotherapeutic
      agents, antifolates and nucleotide analogs, but also into factors that influence
      drug distribution in the body, membrane systems that are involved in the
      extrusion of reduced folates, cysteinyl leukotrienes and bile acids, and the
      molecular basis of two hereditary conditions in humans. The review will describe
      the biochemical properties, drug resistance activities and potential in vivo
      functions of these unusual pumps.

PMID- 14576858
TI  - [Public health and severe acute respiratory syndrome].

PMID- 14576859
TI  - [Air pollution and health].
AB  - The authors have investigated the issue of air pollution and its impact on
      people's health. The study touches such topics as the origins and types of
      pollutants, airspread contaminants, pollutants' biological effect and
      consequences on human health. Although pollution levels have recently shown to be
      lower, they still reflect a major concern for public health. Automobile traffic
      is the main responsible for air pollution and thin dusts are virtually the most
      dangerous particles in the atmosphere. Prevention will only be possible if
      governing bodies adopt effective strategies and public health agents develop
      adequate prevention plans.

PMID- 14576860
TI  - [Organigraphs].

PMID- 14576861
TI  - [Health care quality as perceived by the users of an emergency unit in Rome].
AB  - This study is aimed at assessing health care quality within the St. Eugenio
      Emergency Unit in Rome. The survey covers the months of March, June and November
      2000. Patients were given about 9 thousand forms to fill before and after their
      access. Only 4% of them got to the hospital by ambulance and as many as 85% were
      immediately discharged after the exam. Their expectations were centred primarily
      on the health staff's professional skills, whereas their retroactive judgment
      focused on the poor quality of support services (parking lots, directional signs,
      waiting time), thus neglecting the very professional skills they previously
      considered as a priority.

PMID- 14576862
TI  - [New procedures for improving case sheets editing].
AB  - Case sheets are very important instruments for improving health care quality in
      hospitals. Despite their importance, they are very seldom used and filled in the
      right way. The study is based on an attempt to optimise case sheets editing; it
      implies multiple steps: 1. Project development; implementation of a pattern for
      assessing markers (thoroughness, clearness, reliability and record tracking); 2.
      Delivery of personal research protocols; 3. Early analysis, assessment of
      results; detection of severity; 4. Correctional interventions; 5. Secondary
      analysis; assessment of interventions. Although most indicators have shown an
      improvement, outcomes remain unsatisfactory, given the extent of shortfalls
      before intervention.

PMID- 14576863
TI  - [Behavioural risks in food-related disorders: a teen-age sample from senior high
      schools in Catania, Sicily].
AB  - The authors have carried out a survey on teen-age girls (398 girls aged 15-18)
      from five different senior high schools in Catania, Sicily. Students were
      submitted a questionnaire aimed at detecting behaviours at risk as regards food
      related disorders. The most significant data concerned low body weight (20.4%
      having a Body Mass Index < 18.5), drug intake to lose weight (2.5%), self-induced
      vomit or intention to do so (12.1%), as well as a sort of uneasiness to attend
      other schoolmates due to one's own body weight (9.6%). These variables might
      reflect risk indicators as regards food-related disorders.

PMID- 14576864
TI  - [Diffusion of biological agents in air in a closed environment and related
      pathologies].
AB  - This study is focused on some biological factors, liable to increase health risks
      within specific indoor settings. The authors describe the pathologies associated
      with the exposure to specific indoor biological agents. For lack of threshold
      levels and appropriate regulations on the matter, research has hardly provided
      any reliable results. This study is therefore to be considered a starting point
      for further investigation.

PMID- 14576865
TI  - [The "vicissitudes" of dangerous health wastes].

PMID- 14576866
TI  - Cardiovascular function in elderly patients with chronic chagasic cardiopathy.
AB  - The objective of this work was to verify the degree and type of heart damage of
      elderly chagasic patients seen at an outpatient referral center and to compare
      them with the changes found in young chagasic patients with a similar degree of
      heart damage. Elderly and young patients without advanced cardiopathy presented
      good functional behavior. Elderly patients with advanced cardiopathy had more
      ventricular premature beats (VPB) in 24 h and less functional capacity in the
      exercise test than young patients of the same subgroup. There was a higher
      occurrence of effort-induced VPB and a lower prevalence of severe forms in
      elderly men, suggesting that Chagas' disease may have a worse evolution in males.
      The association of cardiac damage characteristic of aging with the secondary
      damage due to Chagas' disease could explain the greater functional damage found
      in elderly chagasic patients. Thus, it appears that the physiopathological
      components of Chagas' disease do have an influence on the clinical course of
      cardiopathy in the elderly population.

PMID- 14576867
TI  - [Leishmania (Viannia) braziliensis in naturally infected dogs].
AB  - Eight dogs from Marica Municipality (RJ), with suggestive lesion of American
      tegumentary leishmaniasis were studied by parasitological and serological
      methods. Leishmania spp was found in six dogs by in vitro cultivation. Specific
      antibodies were detected in six dogs by ELISA and in two by indirect
      immunofluorescence. Five canine isolates were found to belong to the same
      zymodeme as Leishmania (Viannia) braziliensis. The authors suggest that
      clinically suspect dogs should be followed-up in an attempt to confirm the
      diagnostic of canine tegumentary leishmaniasis.

PMID- 14576868
TI  - [Parasitological and morphological characteristics of Brazilian strains of
      Schistosoma mansoni in Mus musculus].
AB  - Aiming to determine parasitological and morphological differences between
      Brazilian strains (CMO, CM and BE) of Schistosoma mansoni the following
      parameters were studied: prepatent period, kinetics of egg releasing in feces,
      intestinal oogram, infectivity and the morphology of adult worms. No statistical
      difference (p>0.05) was found regarding the mean prepatent period (44 and 46
      days) and infectivity (26% and 29%). All strains showed a higher concentration of
      trapped eggs in the small intestine than large intestine (p<0.05). All
      characteristics of the reproductive system and suckers of male worms presented
      significant differences (p<0.05). CMO strain was smaller in all measurements.
      Females showed significant differences (p<0.05) in the larger diameter of the
      eggs, in the area and perimeter of the spine egg and in the oral sucker area. We
      conclude that differences in strains can be expressed even when the strains have
      been cycled for several generations under laboratory conditions.

PMID- 14576869
TI  - [Prevalence of hepatitis B virus markers within household contacts in the State
      of Amazonas].
AB  - The aim of our investigation was to evaluate, with a prevalence study, the modes
      of transmission of Hepatitis B virus (HBV), within infected subjects and their
      household contacts in the State of Amazon, western Brazilian Amazon. We studied
      97 index cases and 258 household contacts. Out of the 258 household contacts of
      HBV, 51.6% had serological markers of a past infection, 12.0% signs of active
      infection, suggesting that the virus circulates within household members. The
      high prevalence among siblings (23.6%) demonstrates the importance of personal
      contact in the transmission of this virus. Another indirect indicator of intra
      familial transmission was the high prevalence of HBV markers within contacts of a
      fulminant hepatitis. The vertical transmission of HBV in our region may or may
      not occur, but if it does it as a rare event. Our results demonstrate the
      importance of the presence of HBV, and demand other investigations to clarify the
      inter-familial transmission of these viruses in our region.

PMID- 14576870
TI  - [Evaluation of cellular immune response in patients with recurrent candidiasis].
AB  - Recurrent cutaneous or mucosal candidiasis is characterized by the occurrence of
      at least four candidiasis episodes within a one-year period. The factors involved
      in recurrence of infection are still unknown. In the present study the
      lymphoproliferative response and the IFN-gamma production by candidiasis patients
      were evaluated. The stimulation index of mononuclear cell cultures of candidiasis
      patients stimulated with Candida albicans antigen, PPD and TT were 6 +/- 8, 17 +/
      20 and 65 +/- 30, respectively. The addition of monoclonal antibody anti-IL-10
      to Candida albicans antigen stimulated cultures raised the lymphoproliferative
      response from 735 +/- 415 to 4143 +/- 1746 cpm. The IFN-gamma production by cells
      of candidiasis patients stimulated with Candida albicans antigen was 162 +/- 345
      pg/ml. Candidiasis patients have an impairment in the lymphoproliferative
      response specific to C. albicans antigen and on IFN-gamma production and the
      lymphoproliferative response can be partially restored, in vitro, by IL-10
      neutralization.

PMID- 14576871
TI  - Production of septal fibrosis of the liver by means of foreign protein injections
      into rats.
AB  - Similarities and differences in antigenic humoral responses and electrophoretic
      patterns between Capillaria hepatica and pig-serum were investigated as a
      contribution to the understanding of hepatic fibrosis induced by the parenteral
      administration of foreign proteins. Only two out of 10 rats receiving repeated
      intraperitoneal injections of an extract of Capillaria hepatica-infected mouse
      liver presented septal hepatic fibrosis (20%). Under the same experimental
      conditions, 4 out of 9 rats (44.4%) developed septal fibrosis following whole pig
      serum administration. Injections of normal mouse liver extracts did not result in
      hepatic fibrosis. Since a 100% septal fibrosis rate is observed in experimentally
      Capillaria hepatica-infected rats, it appeared that Capillaria hepatica products
      continuously released from inside the liver creates a much more effective
      fibrosis inducing mechanism than the parenteral administration of such factors.
      Thus, repeated peritoneal administration of a foreign protein to rats would not
      reveal the full fibrogenic potential it may have under natural conditions.

PMID- 14576872
TI  - [Malaria outside the Brazilian Amazonian region: the situation in Santa Catarina
      State].
AB  - This study aimed to evaluate the malaria epidemiological aspects in Santa
      Catarina State, Brazil, by using National Health Foundation data from 1996 to
      2001. From 4,707 thick smears analyzed 5.5% were positive. Plasmodium vivax was
      found in 69.0%; Plasmodium falciparum in 25.6%, mixed infection with both in 5%,
      and Plasmodium malariae in only 0.4%. It was observed that 67.4% were
      heterochthonous cases and 32.6% autochthonous cases. In recent years, the
      incidence of heterochthonous cases has increased. The majority of these cases
      come from the Brazilian Amazon region and the remainder from African countries.
      However, the municipalities of Joinville, Blumenau, Sao Francisco do Sul and
      Florianopolis registered higher rates of autochthonous cases in 1996/1997.
      Control and epidemiological surveillance are necessary to prevent the
      reintroduction of Plasmodium in this region. It would be useful to investigate
      each epidemiological setting in order to prevent the reappearance of the disease
      in areas currently considered under control.

PMID- 14576873
TI  - [Clinical and diagnostic aspects of American tegumentary leishmaniosis in
      soldiers simultaneously exposed to the infection in the Amazon Region].
AB  - Military exercises in the forest of the Amazon region constitute an important
      factor in the incidence of American cutaneous leishmaniasis in this region. This
      report describes 48 cases of American tegumentary leishmaniosis. All these
      patients acquired the disease after military exercises in the Amazon. The mean
      incubation time was 27.6 days. The lesions were predominantly in the upper
      extremities, face and neck. The majority of patients presented two lesions.
      Ulcers were the most common clinical manifestation. The diagnosis was obtained
      through skin smears of the lesions. A total of 43 cases (89.6 %) were found to be
      positive.

PMID- 14576874
TI  - [Aquatic animals of medical importance in Brazil].
AB  - The injuries caused by venomous and poisonous aquatic animals may provoke
      important morbidity in the victim. The cnidarians (jellyfishes, especially
      cubomedusas and Portuguese-Man-of-War) caused nearly 25% of 236 accidents by
      marine animals, while sea urchins were responsible for about 50% and catfish,
      stingrays and scorpionfish nearly 25%). In freshwater, stingrays and catfish
      cause injuries with a very similar mechanism to the poisoning and the effects of
      the toxins of marine species. In a series of about 200 injuries observed among
      freshwater fishermen, nearly 40% were caused by freshwater catfish, 5% freshwater
      stingrays and 55% by traumatogenic fish, such as piranhas and trairas. The author
      presents the aquatic animals that cause injuries to humans in Brazil, the
      clinical aspects of the envenoming and the first measures for the control of the
      severe pain observed mainly in the accidents caused by cnidarians and venomous
      fishes.

PMID- 14576875
TI  - [Epidemiology of hematogenous infections due to Candida spp].
AB  - Candida spp is associated to almost 80% of all nosocomial fungal infections and
      is considered a major cause of blood stream infections. Candida spp is the fourth
      most common cause of blood stream infections in the United States, where this
      agent is responsible for 8% of all invasive infections documented in this site.
      At the present, non-albicans species are related to at least 50% of all invasive
      infections due to Candida spp and they present differences in terms of clinical
      outcome as well as susceptibility to antifungal drugs. The crude mortality rate
      of candidemia is between 40 and 60% which makes this infection an important
      challenge for all clinicians from tertiary care hospitals of diverse different
      countries.

PMID- 14576876
TI  - Autochthonous Chagas' disease in Santa Catarina State, Brazil: report of the
      first case of digestive tract involvement.
AB  - We report the first case of digestive tract pathology (megaesophagus) determined
      by Trypanosoma cruzi infection in Santa Catarina State, southern Brazil. A 63
      year-old female had presumptive clinical diagnosis of Chagas' disease, which was
      confirmed by imaging (endoscopy and esophagogram) and immunological methods.
      Further molecular diagnosis was carried out with esophagus and blood samples
      collected during corrective surgery. Polymerase chain reaction tested positive
      for Trypanosoma cruzi in both esophagus and buffy coat samples.

PMID- 14576877
TI  - [Trypanosoma cruzi high parasitemia in patient with systemic lupus
      erythematosus].
AB  - A case of Trypanosoma cruzi high parasitemia in patient with systemic lupus
      erythematosus is reported. A xenodiagnostic test was useful in the identification
      of high and uncommon parasitemia, and Benznidazole was able to reduce the
      parasitemia. Benznidazole can be an alternative to control the Trypanosoma cruzi
      high parasitemia in people with autoimmune disease and immunosuppression.

PMID- 14576878
TI  - [Environmental contamination by helminth eggs and larvae in dog feces from
      central area of Cassino beach, Rio Grande do Sul].
AB  - In order to investigate the presence of helminths agents of parasitic zoonoses,
      were examined 237 fecal samples of dogs from central area of the main beach of
      south coast of Rio Grande do Sul State. The eggs and larvae of genus Ancylostoma
      (71.3%) and Trichuris (32.5%) and Toxocara eggs (9.3%) were the most prevalent
      parasites detected.

PMID- 14576879
TI  - [Frequency of intestinal parasites in samples of lettuce (Lactuca sativa)
      commercialized in Lavras, Minas Gerais State].
AB  - The aim of this study was to evaluate the parasitological contamination in
      samples of lettuce (Lactuca sativa) commercialized in Lavras city, Minas Gerais.
      The samples of lettuce showed low hygienic conditions, indicated by the presence
      of parasites of animal or human origin and high concentration of fecal coliforms.

PMID- 14576880
TI  - [Influence of specific treatment of intestinal parasites and schistosomiasis on
      prevalence in students in Barra de Santo Antonio, AL].
AB  - From a total of 1,020 students examined, 983 (92%) showed positive results for at
      least one species of parasite. Six months after treatment, a sample of 383
      students (37.5%) was reevaluated and 347 (90.6%) presented positive results.
      There was no significant change in prevalence before and after treatment,
      although the number of individuals that had multiple parasitism was significantly
      lower in the second sample.

PMID- 14576881
TI  - Parasitoids of Ophyra aenescens (Wiedemann) (Diptera: Muscidae): fly of medical
      sanitary importance collected in State of Goias, Brazil.
AB  - The objective of the study was to report the first occurrence of the parasitoid
      Brachymeria podagrica in pupae of Ophyra aenescens, a fly of medical-sanitary
      importance. Human feces was used as bait to collect the insects. In the study 20
      pupae of Ophyra aenescens (Wiedemann) (Diptera: Muscidae) were obtained, of which
      20% of the total yielded the parasitoid Brachymeria podagrica (Hymenoptera:
      Chalcididae).

PMID- 14576882
TI  - The presence of Lutzomyia longipalpis in a focus of American visceral
      leishmaniasis where the only proven vector is Lutzomyia cruzi. Corumba, Mato
      Grosso do Sul State.
AB  - The present communication reports the presence of Lutzomyia longipalpis in
      Corumba, Mato Grosso do Sul, where the principal vector is Lutzomyia cruzi.

PMID- 14576883
TI  - Magnetic resonance imaging of cerebellar schistosomiasis mansoni.

PMID- 14576884
TI  - The making of a convention on tobacco control.

PMID- 14576885
TI  - Sugar revisited -- again.

PMID- 14576886
TI  - Introducing auto-disable syringes to the national immunization programme in
      Madagascar.
AB  - OBJECTIVE: To evaluate the safety and coverage benefits of auto-disable (AD)
      syringes, weighed against the financial and logis- tical costs, and to create
      appropriate health policies in Madagascar. METHODS: Fifteen clinics in
      Madagascar, trained to use AD syringes, were randomized to implement an AD
      syringe only, mixed (AD syringes used only on non-routine immunization days), or
      sterilizable syringe only (control) programme. During a five-week period, data on
      administered vaccinations were collected, interviews were conducted, and
      observations were recorded. FINDINGS: The use of AD syringes improved coverage
      rates by significantly increasing the percentage of vaccines administered on non
      routine immunization days (AD-only 4.3%, mixed 5.7%, control 1.1% (P<0.05)). AD
      only clinics eliminated sterilization sessions for vaccinations, whereas mixed
      clinics reduced the number of sterilization sessions by 64%. AD syringes were
      five times more expensive than sterilizable syringes, which increased AD-only and
      mixed clinics' projected annual injection costs by 365% and 22%, respectively.
      However, introducing AD syringes for all vaccinations would only increase the
      national immunization budget by 2%. CONCLUSION: The use of AD syringes improved
      vaccination coverage rates by providing ready-to-use sterile syringes on non
      routine immunization days and decreasing the number of sterilization sessions,
      thereby improving injection safety. The mixed programme was the most beneficial
      approach to phasing in AD syringes and diminishing logistical complications, and
      it had minimal costs. AD syringes, although more expensive, can feasibly be
      introduced into a developing country's immunization programme to improve
      vaccination safety and coverage.

PMID- 14576887
TI  - Labour complications remain the most important risk factors for perinatal
      mortality in rural Kenya.
AB  - OBJECTIVES: To identify and quantify risk factors for perinatal mortality in a
      Kenyan district hospital and to assess the proportion of perinatal deaths
      attributable to labour complications, maternal undernutrition, malaria, anaemia
      and human immunodeficiency virus (HIV). METHODS: A cross-sectional study of 910
      births was conducted between January 1996 and July 1997 and risk factors for
      perinatal mortality were analysed. FINDINGS: The perinatal mortality rate was 118
      per 1000 births. Complications of labour such as haemorrhage, premature rupture
      of membranes/premature labour, and obstructed labour/ malpresentation increased
      the risk of death between 8- and 62-fold, and 53% of all perinatal deaths were
      attributable to labour complications. Placental malaria and maternal HIV, on the
      other hand, were not associated with perinatal mortality. CONCLUSIONS: Greater
      attention needs to be given to the quality of obstetric care provided in the
      rural district-hospital setting.

PMID- 14576888
TI  - Changes in morbidity and medical care utilization after the recent economic
      crisis in the Republic of Korea.
AB  - OBJECTIVE: To examine and quantify the impact of the recent economic crisis on
      morbidity and medical care utilization in the Republic of Korea. METHODS: 22 675
      people from 6791 households and 43 682 people from 12 283 households were
      questioned for two nationwide surveys that took place in 1995 and 1998,
      respectively. A separate sample pretest-posttest design was used and we conducted
      c2 test and logistic regression analysis after controlling for the maturation
      effect of the morbidity and medical care utilization. FINDINGS: The morbidity
      rates of chronic disease and acute disease increased significantly by 27.1% and
      9.5%, respectively, whereas the utilization rates of outpatient and inpatient
      services decreased by 15.1% and 5.2%, respectively. In particular, the pace of
      decline in the utilization rate of outpatient services varied depending on the
      type of disease: morbidity rates for mental and behavioural disorders were 13.7%;
      for cardiovascular disease, 7.1%; and for injury, 31.6%. CONCLUSION: After the
      Republic of Korean economic crisis, the morbidity and medical care utilization
      rates changed significantly but the degree of change depended on the type of
      disease or service. The time-dependent relationship between the national economy
      and the morbidity and medical care utilization rates needs to be further
      investigated.

PMID- 14576889
TI  - Annual risk of tuberculous infection in the northern zone of India.
AB  - OBJECTIVE: To estimate the annual risk of infection with tubercle bacilli in the
      northern zone of India. METHODS: A community-based cross-sectional tuberculin
      survey was conducted among children aged 1-9 years who lived in a sample of
      villages and urban blocks of six selected districts in a defined north zone of
      India. A two-stage cluster sampling method was used to select rural and urban
      clusters. A total of 48 624 children in 598 clusters were subjected to tuberculin
      testing with one tuberculin unit (1 TU) of PPD RT23 stabilized with Tween 80. The
      maximum transverse diameter of induration was measured about 72 hours after the
      test. FINDINGS: Among the 48 624 test-read children, 22 064 (45.4%) had a bacille
      Calmette-Gu rin (BCG) scar. On the basis of the frequency distribution of
      tuberculin reaction size among 25 816 children without a BCG scar, the prevalence
      of infection with tubercle bacilli was estimated as 10.3%. The annual risk of
      infection was computed as 1.9%. The proportion of infected children was
      significantly higher in urban than rural areas. CONCLUSION: The high rate of
      tuberculous infection in the north zone of India suggests the need for further
      intensification of tuberculosis control efforts on a sustained and long-term
      basis.

PMID- 14576890
TI  - The silent burden of anaemia in Tanzanian children: a community-based study.
AB  - OBJECTIVE: To document the prevalence, age-distribution, and risk factors for
      anaemia in Tanzanian children less than 5 years old, thereby assisting in the
      development of effective strategies for controlling anaemia. METHODS: Cluster
      sampling was used to identify 2417 households at random from four contiguous
      districts in south-eastern United Republic of Tanzania in mid-1999. Data on
      various social and medical parameters were collected and analysed. FINDINGS:
      Blood haemoglobin concentrations (Hb) were available for 1979 of the 2131 (93%)
      children identified and ranged from 1.7 to 18.6 g/dl. Overall, 87% (1722) of
      children had an Hb <11 g/dl, 39% (775) had an Hb <8 g/dl and 3% (65) had an Hb <5
      g/dl. The highest prevalence of anaemia of all three levels was in children aged
      6-11 months, of whom 10% (22/226) had an Hb <5 g/dl. However, the prevalence of
      anaemia was already high in children aged 1-5 months (85% had an Hb <11 g/dl, 42%
      had an Hb <8 g/dl, and 6% had an Hb <5 g/dl). Anaemia was usually asymptomatic
      and when symptoms arose they were nonspecific and rarely identified as a serious
      illness by the care provider. A recent history of treatment with antimalarials
      and iron was rare. Compliance with vaccinations delivered through the Expanded
      Programme of Immunization (EPI) was 82% and was not associated with risk of
      anaemia. CONCLUSION: Anaemia is extremely common in south-eastern United Republic
      of Tanzania, even in very young infants. Further implementation of the Integrated
      Management of Childhood Illness algorithm should improve the case management of
      anaemia. However, the asymptomatic nature of most episodes of anaemia highlights
      the need for preventive strategies. The EPI has good coverage of the target
      population and it may be an appropriate channel for delivering tools for
      controlling anaemia and malaria.

PMID- 14576891
TI  - Injury prevention counselling to improve safety practices by parents in Mexico.
AB  - OBJECTIVES: To evaluate the effectiveness of educational counselling programmes
      aimed at increasing parents' practice of childhood safety in Monterrey, Mexico,
      and to provide information aimed at helping to improve the effectiveness of
      future efforts in this field. METHODS: Three different counselling programmes
      were designed to meet the needs of the upper, middle and lower socioeconomic
      strata. Evaluation involved the use of baseline questionnaires on parents'
      existing safety-related practices for intervention and control groups and the
      administration of corresponding questionnaires after the programmes had been
      carried out. FINDINGS: Data were obtained on 1124 children before counselling
      took place and on 625 after it had been given. Overall safety scores (% safe
      responses) increased from 54% and 65% for the lower and upper socioeconomic
      strata, respectively, before counselling to 62% and 73% after counselling (P
      <0.001 for all groups). Improvements occurred both for activities that required
      caution and for activities that required the use of safety-related devices (e.g.
      helmets, car seats). However, scores for the use of such devices remained
      suboptimal even after counselling and there were wide discrepancies between the
      socioeconomic strata. The post-counselling scores for the use of safety-related
      devices were 55%, 38% and 19% for the upper, middle and lower socioeconomic
      strata, respectively. CONCLUSIONS: Brief educational interventions targeting
      parents' practice of childhood safety improved safe behaviours. Increased
      attention should be given to specific safety-related devices and to the safety of
      pedestrians. Educational efforts should be combined with other strategies for
      injury prevention, such as the use of legislation and the improvement of
      environmental conditions.

PMID- 14576892
TI  - Evidence to support a food-based dietary guideline on sugar consumption in South
      Africa.
AB  - Since 1997, South Africa has been developing and implementing food-based dietary
      guidelines for people aged >6 years. The complexity of the population, which
      contains different ethnic groups, as well as the rapid urbanization that is
      taking place, means that food-based dietary guidelines need to consider both
      overnutrition and undernutrition. The initial guidelines did not include guidance
      on sugar, and the Department of Health was not prepared to approve them until
      appropriate guidance on sugar was included. This paper summarizes the evidence
      available for such a guideline and the nature of that evidence. Other low- and
      middle-income countries, particularly those in Africa, may face a similar dilemma
      and might learn from our experience.

PMID- 14576893
TI  - Poverty and common mental disorders in developing countries.
AB  - A review of English-language journals published since 1990 and three global
      mental health reports identified 11 community studies on the association between
      poverty and common mental disorders in six low- and middle-income countries. Most
      studies showed an association between indicators of poverty and the risk of
      mental disorders, the most consistent association being with low levels of
      education. A review of articles exploring the mechanism of the relationship
      suggested weak evidence to support a specific association with income levels.
      Factors such as the experience of insecurity and hopelessness, rapid social
      change and the risks of violence and physical ill-health may explain the greater
      vulnerability of the poor to common mental disorders. The direct and indirect
      costs of mental ill-health worsen the economic condition, setting up a vicious
      cycle of poverty and mental disorder. Common mental disorders need to be placed
      alongside other diseases associated with poverty by policy-makers and donors.
      Programmes such as investment in education and provision of microcredit may have
      unanticipated benefits in reducing the risk of mental disorders. Secondary
      prevention must focus on strengthening the ability of primary care services to
      provide effective treatment.

PMID- 14576894
TI  - Promoting safe motherhood through the private sector in low- and middle-income
      countries.
AB  - The formal private sector could play a significant role in determining whether
      success or failure is achieved in working towards goals for safe motherhood in
      many low- and middle-income settings. Established private providers, especially
      nurses/midwives, have the potential to contribute to safe motherhood practices if
      they are involved in the care continuum. However, they have largely been
      overlooked by policy-makers in low-income settings. The private sector (mainly
      doctors) contributes to overprovision and high Caesarean section rates in
      settings where it provides care to wealthier segments of the population; such
      care is often funded through third-party payment schemes. In poorer settings,
      especially rural areas, private nurses/midwives and the women who choose to use
      them are likely to experience similar constraints to those encountered in the
      public sector - for example, poor or unaffordable access to higher level
      facilities for the management of obstetrical emergencies. Policy-makers at the
      country-level need to map the health system and understand the nature and
      distribution of the private sector, and what influences it. This potential
      resource could then be mobilized to work towards the achievement of safe
      motherhood goals.

PMID- 14576895
TI  - Health research systems: an evolving framework.

PMID- 14576896
TI  - How SARS changed the world in less than six months.

PMID- 14576897
TI  - The Costa Rican health system: low cost, high value.

PMID- 14576898
TI  - WHO news Lee Jong-Wook takes office with pledge for results in countries.

PMID- 14576899
TI  - The role of chemokines and chemokine receptors in eosinophil activation during
      inflammatory allergic reactions.
AB  - Chemokines are important chemotactic cytokines that play a fundamental role in
      the trafficking of leukocytes to sites of inflammation. They are also potent cell
      activating factors, inducing cytokine and histamine release and free radical
      production, a fact that makes them particularly important in the pathogenesis of
      allergic inflammation. The action of chemokines is regulated at the level of
      agonist production and processing as well as at the level of receptor expression
      and coupling. Therefore, an analysis of the ligands must necessarily consider
      receptors. Eosinophils are target cells involved in the allergic inflammatory
      response since they are able to release a wide variety of mediators including CC
      and CXC chemokines and express their receptors. These mediators could damage the
      airway epithelial cells and might be important to stimulate other cells inducing
      an amplification of the allergic response. This review focuses on recently
      emerging data pertaining to the importance of chemokines and chemokine receptors
      in promoting eosinophil activation and migration during the allergic inflammatory
      process. The analysis of the function of eosinophils and their chemokine
      receptors during allergic inflammation might be a good approach to understanding
      the determinants of asthma severity and to developing novel therapies.

PMID- 14576900
TI  - Interruption of the blood-stage cycle of the malaria parasite, Plasmodium
      chabaudi, by protein tyrosine kinase inhibitors.
AB  - Malaria is a devastating disease caused by a unicellular protozoan, Plasmodium,
      which affects 3.7 million people every year. Resistance of the parasite to
      classical treatments such as chloroquine requires the development of new drugs.
      To gain insight into the mechanisms that control Plasmodium cell cycle, we have
      examined the effects of kinase inhibitors on the blood-stage cycle of the rodent
      malaria parasite, Plasmodium chabaudi. In vitro incubation of red blood cells for
      17 h at 37 degrees C with the inhibitors led to a decrease in the percent of
      infected cells, compared to control treatment, as follows: genistein (200 microM 
      75%), staurosporine (1 microM - 58%), R03 (1 microM - 75%), and tyrphostins B44
      (100 microM - 66%) and B46 (100 microM - 68%). All these treatments were shown to
      retard or prevent maturation of the intraerythrocytic parasites. The diverse
      concentration ranges at which these inhibitors exert their effects give a clue as
      to the types of signals that initiate the transitions between the different
      developmental stages of the parasite. The present data support our hypothesis
      that the maturation of the intraerythrocytic cycle of malaria parasites requires
      phosphorylation. In this respect, we have recently reported a high Ca2+
      microenvironment surrounding the parasite within red blood cells. Several kinase
      activities are modulated by Ca2+. The molecular identification of the targets of
      these kinases could provide new strategies against malaria.

PMID- 14576901
TI  - Screening for mutations in human alpha-globin genes by nonradioactive single
      strand conformation polymorphism.
AB  - Point mutations and small insertions or deletions in the human alpha-globin genes
      may produce alpha-chain structural variants and alpha-thalassemia. Mutations can
      be detected either by direct DNA sequencing or by screening methods, which select
      the mutated exon for sequencing. Although small (about 1 kb, 3 exons and 2
      introns), the alpha-globin genes are duplicate (alpha2 and alpha1) and highly G-C
      rich, which makes them difficult to denature, reducing sequencing efficiency and
      causing frequent artifacts. We modified some conditions for PCR and
      electrophoresis in order to detect mutations in these genes employing
      nonradioactive single-strand conformation polymorphism (SSCP). Primers previously
      described by other authors for radioactive SSCP and phast-SSCP plus denaturing
      gradient gel electrophoresis were here combined and the resultant fragments (6
      new besides 6 original per alpha-gene) submitted to silver staining SSCP. Nine
      structural and one thalassemic mutations were tested, under different conditions
      including two electrophoretic apparatus (PhastSystem and GenePhor, Amersham
      Biosciences), different polyacrylamide gel concentrations, run temperatures and
      denaturing agents, and entire and restriction enzyme cut fragments. One hundred
      percent of sensitivity was achieved with four of the new fragments formed, using
      the PhastSystem and 20% gels at 15 degree C, without the need of restriction
      enzymes. This nonradioactive PCR-SSCP approach showed to be simple, rapid and
      sensitive, reducing the costs involved in frequent sequencing repetitions and
      increasing the reliability of the results. It can be especially useful for
      laboratories which do not have an automated sequencer.

PMID- 14576902
TI  - Comparative sequence analysis of the P-, M- and L-coding region of the measles
      virus CAM-70 live attenuated vaccine strain.
AB  - Measles virus is a highly contagious agent which causes a major health problem in
      developing countries. The viral genomic RNA is single-stranded, nonsegmented and
      of negative polarity. Many live attenuated vaccines for measles virus have been
      developed using either the prototype Edmonston strain or other locally isolated
      measles strains. Despite the diverse geographic origins of the vaccine viruses
      and the different attenuation methods used, there was remarkable sequence
      similarity of H, F and N genes among all vaccine strains. CAM-70 is a Japanese
      measles attenuated vaccine strain widely used in Brazilian children and produced
      by Bio-Manguinhos since 1982. Previous studies have characterized this vaccine
      biologically and genomically. Nevertheless, only the F, H and N genes have been
      sequenced. In the present study we have sequenced the remaining P, M and L genes
      (approximately 1.6, 1.4 and 6.5 kb, respectively) to complete the genomic
      characterization of CAM-70 and to assess the extent of genetic relationship
      between CAM-70 and other current vaccines. These genes were amplified using long
      range or standard RT-PCR techniques, and the cDNA was cloned and automatically
      sequenced using the dideoxy chain-termination method. The sequence analysis
      comparing previously sequenced genotype A strains with the CAM-70 Bio-Manguinhos
      strain showed a low divergence among them. However, the CAM-70 strains (CAM-70
      Bio-Manguinhos and a recently sequenced CAM-70 submaster seed strain) were
      assigned to a specific group by phylogenetic analysis using the neighbor-joining
      method. Information about our product at the genomic level is important for
      monitoring vaccination campaigns and for future studies of measles virus
      attenuation.

PMID- 14576903
TI  - Production of a cloned calf from a fetal fibroblast cell line.
AB  - The present study examined the in vitro and in vivo development of bovine nuclear
      transferred embryos. A bovine fetal fibroblast culture was established and used
      as nucleus donor. Slaughterhouse oocytes were matured in vitro for 18 h before
      enucleation. Enucleated oocytes were fused with fetal fibroblasts with an
      electric stimulus and treated with cytochalasin D and cycloheximide for 1 h
      followed by cycloheximide alone for 4 h. Reconstructed embryos were cultured for
      7-9 days and those which developed to blastocysts were transferred to recipient
      cows. Of 191 enucleated oocytes, 83 (43.5%) were successfully fused and 24
      (28.9%) developed to blastocysts. Eighteen freshly cloned blastocysts were
      transferred to 14 recipients, 5 (27.8%) of which were pregnant on day 35 and 3
      (16.7%) on day 90. Of the three cows that reached the third trimester, one
      recipient died of hydrallantois 2 months before term, one aborted fetus was
      recovered at 8 months of gestation, and one delivered by cesarian section a
      healthy cloned calf. Today, the cloned calf is 15 months old and presents normal
      body development (378 kg) and sexual behavior (libido and semen characteristics).

PMID- 14576904
TI  - Antioxidant status of dog aqueous humor after extracapsular lens extraction.
AB  - We determined the antioxidant status of the aqueous humor after extracapsular
      lens extraction in 14 mongrel dogs weighing about 10 kg. The animals were
      examined by slit lamp biomicroscopy, applanation tonometry and indirect
      ophthalmoscopy. One eye was submitted to conventional extracapsular lens
      extraction and the other was used as control. Samples of aqueous humor were
      obtained by anterior chamber paracentesis before and at days 1, 2, 3, 7 and 15
      after surgery. Total antioxidant status was determined as the capacity of aqueous
      humor to inhibit free radical generation by 2,2-azobis(2-amidopropane) chlorine.
      Ascorbic acid concentration was measured by HPLC with UV detection. Protein
      content was determined with the biuret reagent. Statistical analysis was
      performed by ANOVA followed by the Tukey-Kramer test. Protein concentration
      increased from 0.61 to 22 mg/ml 24 h after surgery. These levels were maintained
      and returned to normal at day 7. Total antioxidant capacity was reduced from 50
      to about 30 min until day 3 and at day 7 it was equal to control. Ascorbic acid
      levels were reduced from 252 to about 110 microM and then returned to control
      values at day 15. Considering the importance of ascorbic acid concentration in
      aqueous humor for the maintenance of the antioxidant status of the anterior
      segment of the eye, the decrease of antioxidant defenses suggests that the
      surgical procedures promote an oxidative stress condition in the eye.

PMID- 14576905
TI  - Thiol-independent activity of a cholesterol-binding enterohemolysin produced by
      enteropathogenic Escherichia coli.
AB  - Enterohemolysin produced by Escherichia coli associated with infant diarrhea
      showed characteristics similar to those of thiol-activated hemolysins produced by
      Gram-positive bacteria, including inactivation by cholesterol, lytic activity
      towards eukaryotic cells and thermoinstability. However, enterohemolysin activity
      was not inactivated by oxidation or by SH group-blocking agents (1 mM HgCl2, 1 mM
      iodoacetic acid) and the hemolysin (100 microg/ml) was not lethal to mice, in
      contrast to the lethality of the thiol-activated hemolysin family to animals.
      Earlier reports showed that intravenous injection of partially purified
      streptolysin O preparations (0.2 microg) was rapidly lethal to mice. These
      results suggest that E. coli enterohemolysin is not a thiol-activated hemolysin,
      despite its ability to bind cholesterol, probably due to the absence of free
      thiol-group(s) that characterize the active form of the thiol-activated hemolysin
      molecule.

PMID- 14576906
TI  - Evaluation of stunned and infarcted canine myocardium by real time myocardial
      contrast echocardiography.
AB  - Differentiation between stunned and infarcted myocardium in the setting of acute
      ischemia is challenging. Real time myocardial contrast echocardiography allows
      the simultaneous assessment of myocardial perfusion and function. In the present
      study we evaluated infarcted and stunned myocardium in an experimental model
      using real time myocardial contrast echocardiography. Sixteen dogs underwent 180
      min of coronary occlusion followed by reperfusion (infarct model) and seven other
      dogs were submitted to 20 min of coronary occlusion followed by reperfusion
      (stunned model). Wall motion abnormality and perfusional myocardial defect areas
      were measured by planimetry. Risk and infarct areas were determined by tissue
      staining. In the infarct model, the wall motion abnormality area during coronary
      occlusion (5.52 1.14 cm(2) ) was larger than the perfusional myocardial defect
      area (3.71 1.45 cm (2); P < 0.001). Reperfusion resulted in maintenance of wall
      motion abnormality (5.45 1.41 cm (2); P = 0.43 versus occlusion) and reduction of
      perfusional myocardial defect (1.51 1.29 cm (2); P = 0.004 versus occlusion).
      Infarct size determined by contrast echocardiography correlated with tissue
      staining (r = 0.71; P = 0.002). In the stunned model, the wall motion abnormality
      area was 5.49 0.68 cm (2) during occlusion and remained 5.1 0.63 cm (2) after
      reperfusion (P = 0.07). Perfusional defect area was 2.43 0.79 cm (2) during
      occlusion and was reduced to 0.2 0.53 cm(2) after reperfusion (P = 0.04). 2,3,5
      Triphenyl tetrazolium chloride staining confirmed the absence of necrotic
      myocardium in all dogs in the stunned model. Real time myocardial contrast
      echocardiography is a noninvasive technique capable of distinguishing between
      stunned and infarcted myocardium after acute ischemia.

PMID- 14576907
TI  - Modulation of B lymphocyte function by an aqueous fraction of the ethanol extract
      of Cissampelos sympodialis Eichl (Menispermaceae).
AB  - Cissampelos sympodialis Eichl species are used in folk medicine for the treatment
      of asthma, arthritis and rheumatism. In the present study, we investigated the
      immunomodulatory effect of an aqueous fraction of a 70% (v/v) ethanol extract of
      C. sympodialis leaves on B lymphocyte function. The hydroalcoholic extract
      inhibited the in vitro proliferative response of resting B cells induced by LPS
      (IC50 = 17.2  g/ml), anti-delta-dextran (IC50 = 13.9  g/ml) and anti-IgM (IC50 =
      24.3  g/ml) but did not affect the anti-MHC class II antibody-stimulated
      proliferative response of B cell blasts obtained by stimulation with IL-4 and
      anti-IgM. Incubation with the hydroalcoholic extract used at 50  g/ml induced a
      700% increase in intracellular cAMP levels. IgM secretion by resting B cells
      (obtained from normal mice) and polyclonally activated B cells (obtained from
      Trypanosoma cruzi-infected animals) was inhibited by the hydroalcoholic extract.
      The latter were more sensitive to the hydroalcoholic extract since 6.5  g/ml
      induced a 20% inhibition in the response of cells from normal mice while it
      inhibited the response of B cells from infected animals by 75%. The present data
      indicate that the alcoholic extract of C. sympodialis inhibited B cell function
      through an increase in intracellular cAMP levels. The finding that the
      hydroalcoholic extract inhibited immunoglobulin secretion suggests a therapeutic
      use for the extract from C. sympodialis in conditions associated with unregulated
      B cell function and enhanced immunoglobulin secretion. Finally, the inhibitory
      effect of the hydroalcoholic extract on B cells may indicate an anti-inflammatory
      effect of this extract.

PMID- 14576908
TI  - Identification of Mycobacterium bovis antigens by analysis of bovine T-cell
      responses after infection with a virulent strain.
AB  - Purification and characterization of individual antigenic proteins are essential
      for the understanding of the pathogenic mechanisms of mycobacteria and the immune
      response against them. In the present study, we used anion-exchange
      chromatography to fractionate cell extracts and culture supernatant proteins from
      Mycobacterium bovis to identify T-cell-stimulating antigens. These fractions were
      incubated with peripheral blood mononuclear cells (PBMC) from M. bovis-infected
      cattle in lymphoproliferation assays. This procedure does not denature proteins
      and permits the testing of mixtures of potential antigens that could be later
      identified. We characterized protein fractions with high stimulation indices from
      both culture supernatants and cell extracts. Proteins were identified by two
      dimensional gel electrophoresis followed by N-terminal sequencing or MALDI-TOF.
      Culture supernatant fractions containing low molecular weight proteins such as
      ESAT6 and CFP10 and other proteins (85B, MPB70), and the novel antigens TPX and
      TRB-B were associated with a high stimulation index. These results reinforce the
      concept that some low molecular weight proteins such as ESAT6 and CFP10 play an
      important role in immune responses. Also, Rv3747 and L7/L12 were identified in
      high stimulation index cell extract fractions. These data show that protein
      fractions with high lymphoproliferative activity for bovine PBMC can be
      characterized and antigens which have been already described and new protein
      antigens can also be identified in these fractions.

PMID- 14576909
TI  - Validation of the Brazilian Children's Test of Pseudoword Repetition in
      Portuguese speakers aged 4 to 10 years.
AB  - The phonological loop is a component of the working memory system specifically
      involved in the processing and manipulation of limited amounts of information of
      a sound-based phonological nature. Phonological memory can be assessed by the
      Children's Test of Nonword Repetition (CNRep) in English speakers but not in
      Portuguese speakers due to phonotactic differences between the two languages. The
      objectives of the present study were: 1). to develop the Brazilian Children's
      Test of Pseudoword Repetition (BCPR), a Portuguese version of the CNRep, and 2).
      to validate the BCPR by correlation with the Auditory Digit Span Test from the
      Stanford-Binet Intelligence Scale. The BCPR and Digit Span were assessed in 182
      children aged 4-10 years, 84 from Minas Gerais State (42 from a rural region) and
      98 from the city of S o Paulo. There are subject age and word length effects
      causing repetition accuracy to decline as a function of the number of syllables
      of the pseudowords. Correlations between BCPR and Digit Span forward (r = 0.50; P
      <or= 0.01) and backward (r = 0.43; P <or= 0.01) were found, and partial
      correlation indicated that higher BCPR scores were associated with higher Digit
      Span scores. BCPR appears to depend more on schooling, while Digit Span was more
      related to development. The results demonstrate that the BCPR is a reliable
      measure of phonological working memory, similar to the CNRep.

PMID- 14576910
TI  - Arachidonic acid triggers an oxidative burst in leukocytes.
AB  - The change in cellular reducing potential, most likely reflecting an oxidative
      burst, was investigated in arachidonic acid- (AA) stimulated leukocytes. The
      cells studied included the human leukemia cell lines HL-60 (undifferentiated and
      differentiated into macrophage-like and polymorphonuclear-like cells), Jurkat and
      Raji, and thymocytes and macrophages from rat primary cultures. The oxidative
      burst was assessed by nitroblue tetrazolium reduction. AA increased the oxidative
      burst until an optimum AA concentration was reached and the burst decreased
      thereafter. In the leukemia cell lines, optimum concentration ranged from 200 to
      400 microM (up to 16-fold), whereas in rat cells it varied from 10 to 20 microM.
      Initial rates of superoxide generation were high, decreasing steadily and ceasing
      about 2 h post-treatment. The continuous presence of AA was not needed to
      stimulate superoxide generation. It seems that the NADPH oxidase system
      participates in AA-stimulated superoxide production in these cells since the
      oxidative burst was stimulated by NADPH and inhibited by N-ethylmaleimide,
      diphenyleneiodonium and superoxide dismutase. Some of the effects of AA on the
      oxidative burst may be due to its detergent action. There apparently was no
      contribution of other superoxide-generating systems such as xanthine-xanthine
      oxidase, cytochromes p-450 and mitochondrial electron transport chain, as
      assessed by the use of inhibitors. Eicosanoids and nitric oxide also do not seem
      to interfere with the AA-stimulated oxidative burst since there was no systematic
      effect of cyclooxygenase, lipoxygenase or nitric oxide synthase inhibitors, but
      lipid peroxides may play a role, as indicated by the inhibition of nitroblue
      tetrazolium reduction promoted by tocopherol.

PMID- 14576911
TI  - Biological evaluation of recombinant human erythropoietin in pharmaceutical
      products.
AB  - The potencies of mammalian cell-derived recombinant human erythropoietin
      pharmaceutical preparations, from a total of five manufacturers, were assessed by
      in vivo bioassay using standardized protocols. Eight-week-old normocythemic mice
      received a single subcutaneous injection followed by blood sampling 96 h later or
      multiple daily injections with blood sampling 24 h after the last injection.
      Reticulocyte counting by microscopic examination was employed as the end-point
      using the brilliant cresyl blue or selective hemolysis methods, together with
      automated flow cytometry. Different injection schedules were investigated and
      dose-response curves for the European Pharmacopoeia Biological Reference
      Preparation of erythropoietin were compared. Manual and automated methods of
      reticulocyte counting were correlated with respect to assay validity and
      precision. Using 8 mice per treatment group, intra-assay precision determined for
      all of the assays in the study showed coefficients of variation of 12.1-28.4% for
      the brilliant cresyl blue method, 14.1-30.8% for the selective hemolysis method
      and 8.5-19.7% for the flow cytometry method. Applying the single injection
      protocol, a combination of at least two independent assays was required to
      achieve the precision potency and confidence limits indicated by the
      manufacturers, while the multiple daily injection protocol yielded the same
      acceptable results within a single assay. Although the latter protocol using flow
      cytometry for reticulocyte counting gave more precise and reproducible results
      (intra-assay coefficients of variation: 5.9-14.2%), the well-characterized manual
      methods provide equally valid alternatives for the quality control of recombinant
      human erythropoietin therapeutic products.

PMID- 14576912
TI  - Effect of cyproterone acetate on alpha1-adrenoceptor subtypes in rat vas
      deferens.
AB  - Gonadal hormones regulate the expression of alpha1-adrenoceptor subtypes in
      several tissues. The present study was carried out to determine whether or not
      cyproterone acetate, an anti-androgenic agent, regulates the alpha1-adrenoceptor
      subtypes that mediate contractions of the rat vas deferens in response to
      noradrenaline. The actions of subtype selective alpha1-antagonists were
      investigated in vas deferens from control and cyproterone acetate-treated rats
      (10 mg/day, sc, for 7 days). Prazosin (pA2 approximately 9.5), phentolamine (pA2
      approximately 8.3) and yohimbine (pA2 approximately 6.7) presented competitive
      antagonism consistent with activation of alpha1-adrenoceptors in vas deferens
      from both control and treated rats. The pA2 values estimated for WB 4101 (
      approximately 9.5), benoxathian ( approximately 9.7), 5-methylurapidil
      (approximately 8.5), indoramin ( approximately 8.7) and BMY 7378 ( approximately
      6.8) indicate that alpha1A-adrenoceptors are involved in the contractions of the
      vas deferens from control and cyproterone acetate-treated rats. Treatment of the
      vas deferens from control rats with the alpha1B/alpha1D-adrenoceptor alkylating
      agent chloroethylclonidine had no effect on noradrenaline contractions,
      supporting the involvement of the alpha1A-subtype. However, this agent partially
      inhibited the contractions of vas deferens from cyproterone acetate-treated rats,
      suggesting involvement of multiple receptor subtypes. To further investigate
      this, the actions of WB 4101 and chloroethylclonidine were reevaluated in the vas
      deferens from rats treated with cyproterone acetate for 14 days. In these organs
      WB 4101 presented complex antagonism characterized by a Schild plot with a slope
      different from unity (0.65 0.05). After treatment with chloroethylclonidine, the
      complex antagonism presented by WB 4101 was converted into classical competitive
      antagonism, consistent with participation of alpha1A-adrenoceptors as well as
      alpha1B-adrenoceptors. These results suggest that cyproterone acetate induces
      plasticity in the alpha1-adrenoceptor subtypes involved in the contractions of
      the vas deferens.

PMID- 14576913
TI  - Melatonin and N-acetyl-serotonin cross the red blood cell membrane and evoke
      calcium mobilization in malarial parasites.
AB  - The duration of the intraerythrocytic cycle of Plasmodium is a key factor in the
      pathogenicity of this parasite. The simultaneous attack of the host red blood
      cells by the parasites depends on the synchronicity of their development.
      Unraveling the signals at the basis of this synchronicity represents a
      challenging biological question and may be very important to develop alternative
      strategies for therapeutic approaches. Recently, we reported that the synchrony
      of Plasmodium is modulated by melatonin, a host hormone that is synthesized only
      during the dark phases. Here we report that N-acetyl-serotonin, a melatonin
      precursor, also releases Ca2+ from isolated P. chabaudi parasites at micro- and
      nanomolar concentrations and that the release is blocked by 250 mM luzindole, an
      antagonist of melatonin receptors, and 20 mM U73122, a phospholipase C inhibitor.
      On the basis of confocal microscopy, we also report the ability of 0.1 microM
      melatonin and 0.1 microM N-acetyl-serotonin to cross the red blood cell membrane
      and to mobilize intracellular calcium in parasites previously loaded with the
      fluorescent calcium indicator Fluo-3 AM. The present data represent a step
      forward into the understanding of the signal transduction process in the host
      parasite relationship by supporting the idea that the host hormone melatonin and
      N-acetyl-serotonin generate IP3 and therefore mobilize intracellular Ca2+ in
      Plasmodium inside red blood cells.

PMID- 14576914
TI  - A leucine-supplemented diet improved protein content of skeletal muscle in young
      tumor-bearing rats.
AB  - Cancer cachexia induces host protein wastage but the mechanisms are poorly
      understood. Branched-chain amino acids play a regulatory role in the modulation
      of both protein synthesis and degradation in host tissues. Leucine, an important
      amino acid in skeletal muscle, is higher oxidized in tumor-bearing animals. A
      leucine-supplemented diet was used to analyze the effects of Walker 256 tumor
      growth on body composition in young weanling Wistar rats divided into two main
      dietary groups: normal diet (N, 18% protein) and leucine-rich diet (L, 15%
      protein plus 3% leucine), which were further subdivided into control (N or L) or
      tumor-bearing (W or LW) subgroups. After 12 days, the animals were sacrificed and
      their carcass analyzed. The tumor-bearing groups showed a decrease in body weight
      and fat content. Lean carcass mass was lower in the W and LW groups (W = 19.9  
      0.6, LW = 23.1   1.0 g vs N = 29.4   1.3, L = 28.1   1.9 g, P < 0.05). Tumor
      weight was similar in both tumor-bearing groups fed either diet. Western blot
      analysis showed that myosin protein content in gastrocnemius muscle was reduced
      in tumor-bearing animals (W = 0.234   0.033 vs LW = 0.598   0.036, N = 0.623  
      0.062, L = 0.697   0.065 arbitrary intensity, P < 0.05). Despite accelerated
      tumor growth, LW animals exhibited a smaller reduction in lean carcass mass and
      muscle myosin maintenance, suggesting that excess leucine in the diet could
      counteract, at least in part, the high host protein wasting in weanling tumor
      bearing rats.

PMID- 14576915
TI  - Effects of losartan combined with exercise training in spontaneously hypertensive
      rats.
AB  - We investigate whether combined treatment with losartan, an angiotensin II
      receptor blocker, and exercise training (ET) in spontaneously hypertensive rats
      (SHR) would have an additive effect in reducing hypertension and improving
      baroreflex sensitivity when compared with losartan alone. Male SHR (8 weeks old)
      were assigned to 3 groups: sedentary placebo (SP, N = 16), sedentary under
      losartan treatment (SL, N = 11; 10 mg kg-1 day-1, by gavage), and ET under
      losartan treatment (TL, N = 10). ET was performed on a treadmill 5 days/week for
      60 min at 50% of peak VO2, for 18 weeks. Blood pressure (BP) was measured with a
      catheter inserted into the carotid artery, and cardiac output with a microprobe
      placed around the ascending aorta. The baroreflex control of heart rate was
      assessed by administering increasing doses of phenylephrine and sodium
      nitroprusside (iv). Losartan significantly reduced mean BP (178   16 vs 132   12
      mmHg) and left ventricular hypertrophy (2.9   0.4 vs 2.5   0.2 mg/g), and
      significantly increased baroreflex bradycardia and tachycardia sensitivity (1.0  
      0.3 vs 1.7   0.5 and 2.0   0.7 vs 3.2   1.7 bpm/mmHg, respectively) in SL
      compared with SP. However, losartan combined with ET had no additional effect on
      BP, baroreflex sensitivity or left ventricular hypertrophy when compared with
      losartan alone. In conclusion, losartan attenuates hypertension and improves
      baroreflex sensitivity in SHR. However, ET has no synergistic effect on BP in
      established hypertension when combined with losartan, at least at the dosage used
      in this investigation.

PMID- 14576916
TI  - [Four years ago].

PMID- 14576917
TI  - [Pharmaceutical care for drug-related problems in inpatients].
AB  - Drug therapy-induced high morbidity results in pharmacists participating in the
      prevention and solution of drug-related problems (DRPs). OBJECTIVE: To assess DRP
      prevalence amongst inpatients, and the clinical results derived from
      pharmaceutical intervention. METHODS: DRPs detected during 6 months at Hospital
      Comarcal de Sant Bernabe were recorded and classified, and their severity
      established. Pharmaceutical intervention was evaluated by using two codes: impact
      and clinical significance. Interventions were reassessed by another pharmacist
      and a physician, and the degree of agreement was calculated. RESULTS: The
      prevalence of DRPs amongst inpatients was 10.8%. A total of 425 DRPs was
      detected, with a mean of 1.51 DRPs/patient. The highest percentage involved
      inappropriate drugs (26%), overdosing (22%), and inadequate dosing (22%). Eighty
      four percent of DRPs were a severity level 2. Drugs mainly involved were
      antibiotics (21.6%), anti-ulcer agents (21.8%), and analgesic-anti-inflammatory
      compounds (8.1%). In all, 58% of interventions impacted on treatment
      effectiveness, and 42% on toxicity. Intervention acceptance was 91%. Seventy
      percent of interventions were appropriate and highly significant. The percentage
      of agreements in reassessments exceeded 88%. CONCLUSIONS: Pharmaceutical care
      allows DRPs to be prevented and solved. Methodology validation makes it safer in
      daily practice.

PMID- 14576918
TI  - [Therapeutic interchange between angiotensin II receptor blockers in
      institutionalized elderly patients. Implimenting a protocol].
AB  - OBJECTIVE: To assess the effectiveness of a therapeutic interchange protocol for
      angiotensin II receptor blockers (ARB's) in the maintenance of blood pressure
      levels for institutionalized elderly patients diagnosed with hypertension.
      METHODS: A new protocol was discussed by the Pharmacy and Therapeutics Committee,
      and its implementation by the Pharmacy Department was authorized. The protocol
      specifies equivalent doses between drugs and the patients' clinical follow-up.
      Criteria used in the assessment includes: need to change dosage for an ARB
      included in the Pharmacotherapeutic Guide, and blood pressure changes after drug
      interchange. RESULTS: In the absence of hepatic insufficiency, the protocol may
      replace the standard doses of any drugs within this group with losartan 50 mg
      daily. If needed, the dose of losartan may be increased to 100 mg daily divided
      into two doses. Eighteen patients, which represent 10% of all interchange
      operations carried out by the Pharmacy Department, were included in this study.
      Blood pressures both before and after the interchange process show no major
      differences between them. Only two patients required an increase in the dose of
      losartan. CONCLUSION: The implementation of a therapeutic interchange protocol as
      agreed upon by the Pharmacy and Therapeutics Committee allows the clinical follow
      up of patients and therefore facilitates an evaluation of the process. This ARB
      interchange protocol, as suggested for the institutionalized elderly population
      setting, has proven effective in maintaining anti-hypertensive activity.

PMID- 14576919
TI  - [Urinary tract infection in institutionalized elderly patients. Incidence of
      bacterial resistance and risk factors].
AB  - INTRODUCTION: The goal of the present work was to study urinary tract infections
      (UTI) in a sociosanitary center in order to characterize etiology, define
      sensitivity profiles, and study associations between these profiles and various
      clinical parameters. MATERIAL AND METHODS: A prospective study of all urinary
      tract infections at the caring unit of a geriatric sociosanitary center was
      carried out. Antibiograms were performed on all patients in which a UTI was
      suspected, and the association between the isolated organism or E. coli
      resistance with various clinical parameters (gender, bed confinement, recurrence,
      incontinence, neural impairment, basic daily life activities and drug use) was
      studied using a multivariate logistic regression analysis. RESULTS: Escherichia
      coli and Proteus mirabilis are the most commonly isolated organisms (51% and 15%,
      respectively). The former is associated with bed confinement and the female
      gender. The latter shows an inverse relation with recurrence in 90 days.
      Resistance to the antibiotics studied correlates with a number of clinical
      parameters, although associations vary for each antimicrobial agent. Previous use
      of antibiotics and recurrence of infection have no influence on resistance.
      DISCUSSION: Geriatric patients' characteristics may well account for some of the
      results encountered. However, the development of resistance in the center may be
      related to spreading from direct contact between patients. The relationship
      between resistance and drug use may be affected by the external administration,
      rather than in-center administration, of drugs.

PMID- 14576920
TI  - [Stability of prostaglandin E1 when fractioned into polypropylene syringes].
AB  - Prostaglandin E1 is indicated for the temporary maintenance of patent ductus
      arteriosus in newborns with ductus-dependent congenital heart defects. Since the
      standard daily dose is smaller (0.2-0.4 ml) than one ampoule (1 ml), we performed
      a chemical stability study of prostaglandin E1 when it is fractioned into
      polypropylene syringes. Three concentrations were studied: 500 mg/ml (original),
      and 1:2 and 1:4 dilutions in sodium chloride 0.9%. Syringes were kept at 4
      degrees C for 30 days. Prostaglandin E1 levels were determined by using high
      pressure chromatography. In all three formulations, the concentrations underwent
      no statistically significant changes over time (p>0.05). CONCLUSION: PGE1 is
      chemically stable at 4 degrees C for 30 days when fractioned into polypropylene
      syringes, both in the original and the 1:2 and 1:4 diluted formulations.

PMID- 14576921
TI  - [Wasting syndrome in cancer patients: pathophysiology, clinical manifestations
      and drug therapy].
AB  - Wasting is a syndrome related to patient functional impairment that characterizes
      many conditions, including cancer. The development of wasting includes changes in
      the metabolism, as well as in hormones and other cell mediators, which trigger a
      syndrome that cannot be solved by forced nutrient ingestion. The goal of this
      study is to review the pathophysiological components of wasting, as well as its
      clinical manifestations and the available specific drug therapy options for the
      treatment of this condition. To this end, a review of papers published during the
      last four years has been carried out. The treatment of wasting with drugs
      includes a number of combination therapies for the underlying condition,
      nutritional support administration, and specific drug therapy for the wasting
      clinical picture. Currently, the clinical efficacy of cyproheptadine, hydrazine
      and pentoxyfilline in the treatment of anorexia is uncertain. Only progestagen
      derivatives have shown to increase appetite and food intake, and to improve
      nutritional status, in these patients. Corticoids also appear to increase
      appetite, but their effects are short-lasting.

PMID- 14576922
TI  - [Role of allopurinol and rofecoxib in agranulocytosis and acute tubular
      necrosis].
AB  - OBJECTIVE: To report the case of a patient who developed a life-threatening
      agranulocytosis and acute tubular necrosis after the administration of
      allopurinol and rofecoxib. CASE REPORT: After minor surgery, a 70-year-old male
      underwent a routine blood test which encountered: anemia, leucopenia,
      neutropenia, thrombopenia, and altered creatinine levels. Both marrow and renal
      biopsies were performed, yielding the following results: acute tubular necrosis
      and agranulocytosis in the recovery stage. One month and a half before the
      aforementioned surgery a routine blood test had been performed, which showed
      normal values. The patient had then received allopurinol 100 mg/day for around 2
      months, and rofecoxib 2.5 mg/day for 14 days. DISCUSSION: After ruling out other
      possible causes, a diagnosis of iatrogenically induced agranulocytosis and acute
      tubular necrosis was reached. We used a (modified) Karch-Lasagna algorithm with
      both drugs, and found the following imputability values: possible for rofecoxib
      and probable for allopurinol. In view of the widespread use of rofecoxib and COX
      2 inhibitors, despite their recent availability, and of their potential role in
      the severe adverse effects discussed, healthcare professionals must be on the
      alert for the development of symptoms suggesting said or other adverse effects.

PMID- 14576923
TI  - [Hematopoietic progenitor cell transplantation and immune tolerance induction in
      autoimmune diseases].

PMID- 14576924
TI  - [Drug safety. Notes regarding drug surveillance].

PMID- 14576928
TI  - Transduction efficiency of MLV but not of HIV-1 vectors is pseudotype dependent
      on human primary T lymphocytes.
AB  - The success of several gene therapeutic approaches requires efficient
      transduction of human primary T lymphocytes. For this it is important to enhance
      the transduction efficiency, and this can be achieved by various means, mainly
      technical development of transduction procedures and use of different vectors and
      vector pseudotypes. We analyzed the transduction efficiency of an HIV-1 vector
      encoding enhanced green fluorescent protein (GFP) as a marker gene and
      pseudotyped with the envelopes of MLV-A, MLV-10A1, GaLV, RD114, and VSV for human
      primary T lymphocytes in comparison to an MLV vector pseudotyped with the same
      envelopes. Pseudotyping of the MLV vector with the envelopes of 10A1 and GaLV
      resulted in efficient transduction of preactivated human primary T lymphocytes
      (32.4% and 32.7% CD3+/GFP+ cells, respectively) while MLV-A (14.0%), RD114
      (8.8%), and VSV (1.5%) envelopes were less efficient when using titrated vector
      stocks equilibrated to a multiplicity of infection of 1. In contrast, the HIV-1
      vectors pseudotyped with these envelope proteins transduced preactivated T
      lymphocytes with similar efficiency (approx. 20% CD3+/GFP+ cells). Thereby, CD4+
      and CD8+ T lymphocyte subpopulations were transduced at equivalent levels. The
      similar performance of the different HIV-1 vector pseudotypes may be due in part
      to the similar half-lives of the vector particles. Independently of the envelope
      used for pseudotyping neither the MLV nor the HIV-1 vectors yielded any
      significant transduction in nonactivated T lymphocytes (below 0.55% of GFP+
      cells)

PMID- 14576929
TI  - High sexual signalling rates of young individuals predict extended life span in
      male Mediterranean fruit flies.
AB  - In a laboratory study, we monitored the lifetime sexual signalling
      (advertisement) of wild male Mediterranean fruit flies, and we tested the
      hypothesis that high lifetime intensity of sexual signalling indicates high
      survival probabilities. Almost all males exhibited signalling and individual
      signalling rates were highly variable from the beginning of the adults' maturity
      and throughout their life span (average life span 62.3 days). Sexual signalling
      rates after day 10 (peak maturity) were consistently high until about 1 week
      before death. There was a positive relationship between daily signalling rates
      and life span, and an increase in signalling level by one unit over all times was
      associated with an approximately 50% decrease in mortality rate. Signalling rates
      early in adult life (day 6-20) were higher in the longest-lived than in the
      shortest-lived flies. These results support the hypothesis that intense sexual
      signalling indicates longer life span. We discuss the importance of age-specific
      behavioural studies for understanding the evolution of male life histories.

PMID- 14576930
TI  - Extensive summer water pulses do not necessarily lead to canopy growth of Great
      Basin and northern Mojave Desert shrubs.
AB  - Plant species and functionally related species groups from arid and semi-arid
      habitats vary in their capacity to take up summer precipitation, acquire nitrogen
      quickly after summer precipitation, and subsequently respond with
      ecophysiological changes (e.g. water and nitrogen relations, gas exchange). For
      species that respond ecophysiologically, the use of summer precipitation is
      generally assumed to affect long-term plant growth and thus alter competitive
      interactions that structure plant communities and determine potential responses
      to climate change. We assessed ecophysiological and growth responses to large
      short-term irrigation pulses over one to three growing seasons for several
      widespread Great Basin and northern Mojave Desert shrub species: Chrysothamnus
      nauseosus, Sarcobatus vermiculatus, Atriplex confertifolia, and A. parryi. We
      compared control and watered plants in nine case studies that encompassed adults
      of all four species, juveniles for three of the species, and two sites for two of
      the species. In every comparison, plants used summer water pulses to improve
      plant water status or increase rates of functioning as indicated by other
      ecophysiological characters. Species and life history stage responses of
      ecophysiological parameters (leaf N, delta15N, delta13C, gas exchange, sap flow)
      were consistent with several previous short-term studies. However, use of summer
      water pulses did not affect canopy growth in eight out of nine comparisons,
      despite the range of species, growth stages, and site conditions. Summer water
      pulses affected canopy growth only for C. nauseosus adults. The general lack of
      growth effects for these species might be due to close proximity of groundwater
      at these sites, co-limitation by nutrients, or inability to respond due to
      phenological canalization. An understanding of the connections between short-term
      ecophysiological responses and growth, for different habitats and species, is
      critical for determining the significance of summer precipitation for desert
      community dynamics.

PMID- 14576931
TI  - On the use of spleen mass as a measure of avian immune system strength.
AB  - The avian spleen has been frequently used in studies of avian ecology,
      parasitology, and evolution to infer immune system strength in birds.
      Traditionally, it has been assumed that a large spleen is representative of a
      strong immune system and conclusions based on this assumption have led to
      interesting interpretations of the role of disease and parasitism, for example in
      predator-prey interactions. This assumption of a positive relationship between
      spleen size and immune system strength has been made despite an incomplete
      understanding of the physiology of the avian spleen and little evidence of the
      validity of such an assumption. In this response, we demonstrate that the
      assumption of a predictable, positive relationship between spleen size and
      immunocompetence may be unjustified based on what is known of avian splenology.
      We also review recent research that may indicate that the inverse of the above
      assumption is true and we discuss general limitations of the use of the spleen as
      an indicator of immune system strength in birds. Finally, we make recommendations
      for future research topics in this field of study.

PMID- 14576932
TI  - Breeding suppression in free-ranging grey-sided voles under the influence of
      predator odour.
AB  - The breeding suppression hypothesis predicts that females of certain small mammal
      species will reduce reproduction as a response to the odour of a specialised
      mammalian predator. This was tested in a field experiment with grey-sided voles
      (Clethrionomys rufocanus) during three summer seasons (1997-1999) in the
      subalpine tundra of northern Norway, which is a natural habitat of this species.
      In a first phase free-ranging voles in six unfenced 1-ha plots were monitored by
      live-trapping from June to August each year. In a second phase from August to
      September, three of the plots were sprayed with weasel (Mustela nivalis) odour to
      simulate increased apparent predation risk, while the remaining three plots
      served as untreated controls. On all plots voles were individually marked with
      ear tattoos and were regularly live-trapped during the whole breeding season to
      follow their performance. On the treatment plots the recruitment rate of
      juveniles did not increase in late summer as it did on the control plots. The
      proportion of reproductively non-active adult females was significantly higher on
      the treatment plots for both old and young females. Our results thus verify the
      breeding suppression hypothesis for the first time under natural conditions.
      However, the response in overwintered females is in conflict with the original
      hypothesis because the assumed fitness benefits from breeding delayed until the
      next season are inaccessible to them. As an alternative explanation we propose a
      short-term response of reduced activity and interrupted breeding until the
      predator has exploited and left the feeding patch. Such a "duck and cover"
      strategy would increase the fitness of females of all age classes when prey
      habitats are patchy.

PMID- 14576933
TI  - Survival, growth, and escape from herbivory are determined by habitat and
      herbivore species for three Australian woodland plants.
AB  - To understand how plant communities are structured by herbivory it is essential
      to investigate the roles of different herbivores and the responses of a variety
      of plant species in different habitats. We examined the effects of mammalian
      herbivores on survival and growth of transplanted seedlings of two native trees
      (Eucalyptus albensand Callitris glaucophylla), and one native grass (Themeda
      australis) in white box ( E. albens) woodlands in eastern Australia over 3 years.
      Herbivores were manipulated using four fencing treatments that successively
      excluded livestock, macropods, and rabbits from woodland and grassland (cleared
      pasture). Survival was highest in the absence of mammalian herbivores and in
      woodlands, and patterns differed among plant species. Survival of T. australis
      was low, especially in grasslands, and mortality by overgrowth was common in
      ungrazed treatments. All plant species were taller in fenced plots, and
      differences between treatments were greater in grassland. Rabbits and livestock
      had the greatest influence on C. glaucophylla, while T. australis and E. albens
      were most affected by livestock and macropods. We used field data to parameterize
      stage-classified matrix models to predict escape from herbivory (escape height
      >100 cm) for tree species. Reduced herbivory increased the proportion of
      individuals reaching escape height after 15 years. Rate of escape was greater in
      grassland, and this faster growth appeared to counteract much of the negative
      impact of herbivores. While T. australis was unable to escape herbivory, larger,
      ungrazed individuals were more likely to flower and therefore contribute to the
      maintenance of the population. Our results show that habitat and herbivore
      species strongly influence the effect of herbivory on vegetation.

PMID- 14576934
TI  - Characterization of the hrp pathogenicity cluster of Erwinia carotovora subsp.
      carotovora: high basal level expression in a mutant is associated with reduced
      virulence.
AB  - Extracellularly targeted proteins are crucial for virulence of gram-negative
      phytopathogenic bacteria. Erwinia carotovora subsp. carotovora employs the so
      called type II (GSP) pathway to secrete a number of pectinases and cellulases,
      which cause the typical tissue maceration symptoms of soft-rot disease. The type
      III (hrp) pathway is the major virulence determinant in the genera Pseudomonas,
      Ralstonia and Xanthomonas, and in non-macerating species of Erwinia. The hrp
      cluster was recently partially characterized from E. carotovora sp. carotovora,
      and shown to affect virulence during early stages of infection. Here we have
      isolated and characterized 15 hrp genes comprising the remaining part of the
      cluster. The genes hrpL, hrpXY and hrpS were deduced to be transcribed as
      separate units, whereas the 11 remaining genes from hrpJ to hrcU form a single
      large operon. The hrpX gene, which codes for the sensory kinase of the two
      component regulatory locus hrpXY was insertionally inactivated by placing a
      transposon (entranceposon) in the gene. The resulting mutant bacterium expresses
      the hrp genes at high basal level even in a non-inducing medium. This relative
      overexpression was shown to be due to the hrpX::entranceposon insertion causing
      enhanced transcription of the downstream hrpY gene. The hrpX(-)-hrpYC mutant
      bacterium exhibited a slower growth rate and the appearance of disease symptoms
      in infected Arabidopsis plants was delayed, as compared to the wild-type strain.
      The need for hrp gene expression for virulence has been documented in both non
      macerating plant pathogens and in soft-rotting Erwinia sp. but this is the first
      demonstration that high basal-level expression of hrp -regulated genes may
      actually have a negative impact on disease progress in a susceptible host plant.

PMID- 14576935
TI  - Association of gastric and intestinal phenotypic marker expression of gastric
      carcinomas with tumor thymidylate synthase expression and response to
      postoperative chemotherapy with 5-fluorouracil.
AB  - PURPOSE: It is well known that both gastric and intestinal phenotypic markers are
      expressed in gastric carcinomas, irrespective of their histological type. In the
      present study, the associations among phenotypic marker expression of gastric
      carcinomas, tumor thymidylate synthase (TS) expression, and the chemotherapeutic
      response to 5-fluorouracil (5-FU) were examined. METHODS: The gastric and
      intestinal phenotypic marker expression of the tumor was determined by the
      combination of the expression of human gastric mucin (HGM), MUC6, MUC2, and CD10,
      and was evaluated in comparison with tumor TS expression in 137 advanced gastric
      carcinomas in 137 patients (75 with postoperative chemotherapy with 5-FU and 62
      without postoperative chemotherapy). Tumors were classified into the gastric- (G
      ), gastric and intestinal mixed- (GI-), intestinal- (I-), or unclassified- (UC-)
      phenotype according to the immunopositivity of HGM, MUC6, MUC2, and CD10
      stainings. The associations among the gastric and intestinal phenotypic marker
      expression of the tumor, tumor TS expression, effect of postoperative
      chemotherapy with 5-FU, and the patient's prognosis were examined. RESULTS: Of
      the 137 gastric carcinomas, 48 (35.0%), 58 (42.3%), 23 (16.8%), and 8 (5.8%)were
      classified as the G-, GI-, I- and UC-phenotype, respectively. The high TS
      expression of more than 25% tumor cell positivity was found in 25 (52.1%) of the
      48 G-phenotype tumors, 39 (67.2%) of the 58 GI-phenotype tumors, 18 (78.3%) of
      the 23 I-phenotype tumors, and 4 (50.0%) of the 8 UC-phenotype tumors. The I
      phenotype tumors were significantly correlated with the higher rate of the high
      TS expression as compared with the G-phenotype tumors (P<0.05). Among 48 patients
      with the G-phenotype tumor, the 5-year survival rate in patients with and without
      postoperative chemotherapy was 39.7 and 27.8%, respectively. The patients with
      postoperative chemotherapy had a significantly better prognosis than those
      without postoperative chemotherapy (P<0.05). Conversely, there were no
      significant correlations between the presence of postoperative chemotherapy and
      the patient's prognosis among patients with GI-, I-, and UC-phenotype tumors.
      CONCLUSIONS: These results indicate that postoperative chemotherapy with 5-FU
      could be effective for patients with the G-phenotype tumor, since the incidence
      of intratumoral expression of TS, the target enzyme of 5-FU, is significantly low
      in G-phenotype tumors.

PMID- 14576936
TI  - Prevention of vitamin K deficiency bleeding with oral mixed micellar
      phylloquinone: results of a 6-year surveillance in Switzerland.
AB  - In 1995, a new form of vitamin K prophylaxis with two oral doses of 2 mg mixed
      micellar phylloquinone (Konakion MM) on the 1st and 4th day of life was
      introduced in Switzerland. It was hoped that this new galenic preparation of
      phylloquinone would protect infants with insufficient or absent bile acid
      excretion from late vitamin K deficiency bleeding (VKDB). Subsequently, the
      occurrence of VKDB was monitored prospectively between July 1, 1995 and June 30,
      2001 with the help of the Swiss Paediatric Surveillance Unit (SPSU). Over a
      period of 6 years (475,000 deliveries), there were no cases of early (<24 h of
      age), one case of classical (2-7 days of life), and 18 cases of late (1-12 weeks)
      VKDB fulfilling standard case definitions. In 13/18 patients with late VKDB there
      was pre-existing liver disease and in 4/18 patients, parents had refused
      prophylaxis. The incidence of late VKDB for infants with completed Konakion MM
      prophylaxis was 2.31/100,000 (95% CI: 1.16-4.14) and for the entire population
      3.79/100,000 (95% CI: 2.24-5.98). There was only one case of late VKDB after
      complete prophylaxis in an infant without underlying liver disease. CONCLUSION:
      two oral doses of 2 mg of a mixed micellar vitamin K preparation failed to
      abolish VKDB. The recommendations for vitamin K prophylaxis in Switzerland have
      therefore been changed to include a third dose at 4 weeks of age. Starting on
      January 1, 2004, the incidence of vitamin K deficiency bleeding will again be
      monitored prospectively by the Swiss Paediatric Surveillance Unit.

PMID- 14576937
TI  - Immunostaining for the tumour suppressor gene p16 product is a useful marker to
      differentiate melanoma metastasis from lymph-node nevus.
AB  - Upon the introduction of extensive sampling protocols of sentinel node biopsies,
      pathologists are increasingly confronted with small melanoma metastases. Using
      conventional histology, it proves sometimes difficult or impossible to
      differentiate small melanoma metastases from lymph-node nevi. Loss of the tumour
      suppressor gene p16 has been shown to be associated with tumour progression of
      melanoma. We investigated nevus and melanoma cells for the presence of the
      product of the gene p16, using immunohistochemistry. All nevus cells, independent
      of their location (nodal or skin) displayed an extensive nuclear and cytoplasmic
      staining for p16. In contrast, all cells of melanoma metastases, except one skin
      metastasis, lacked nuclear staining for p16. These findings indicate that p16 is
      a reliable marker to distinguish lymph-node nevi from melanoma metastasis.

PMID- 14576938
TI  - The identification of monoclonality in fibrous dysplasia by methylation-specific
      polymerase chain reaction for the human androgen receptor gene.
AB  - The nature of fibrous dysplasia, a well-known and relatively common bone lesion,
      is controversial. We report here the first polymerase chain reaction (PCR)-based
      clonality analysis of fibrous dysplasia in which 11 cases obtained from females
      with a polymorphism at the human androgen receptor gene locus ( HUMARA) were
      examined using a methylation-specific PCR procedure. This assay allowed accurate
      evaluation of the clonality status of this disease by eliminating restriction
      enzyme digestion that had been used previously in conventional HUMARA analysis.
      Eight samples proved to be informative for the assay, and they all showed non
      random X-chromosome inactivation, indicative of a monoclonal pattern. These
      findings demonstrate a clonal origin for fibrous dysplasia, suggesting that the
      disease is a neoplastic lesion rather than a "dysplastic" process, as has been
      generally believed.

PMID- 14576940
TI  - Wegener's granulomatosis presenting with gross hematuria due to prostatitis.

PMID- 14576939
TI  - CDX2 immunoreactivity in primary and metastatic ovarian mucinous tumours.
AB  - The caudal-related homeobox transcription factor CDX2 regulates the
      differentiation of intestinal epithelial cells. Recent studies have suggested
      that CDX-2 immunoreactivity is strictly confined to benign and malignant
      intestinal epithelium. In the present study, we evaluated the prevalence of CDX2
      immunoreactivity in a series of benign, borderline and malignant primary ovarian
      mucinous neoplasms. We tested 62 mucinous tumours of the ovary, including 28
      benign cystadenomas, 18 borderline tumours, 16 adenocarcinomas, 35 serous and
      endometrioid ovarian lesions and 10 ovarian metastases of colonic adenocarcinoma.
      Overall, the CDX2 prevalence in primary mucinous tumours was 79%, including 20 of
      28 (71.5%) cystadenomas, 14 of 18 (77.7%) borderline tumours and 15 of 16 (93.5%)
      adenocarcinomas. Immunoreactivity usually correlated with intestinal
      differentiation of tumour cells, although wide heterogeneity in the distribution
      of immunolabelled cells was noted. No immunoreactivity was observed in serous
      lesions; whereas, 1 of 13 (7.7%) endometrioid adenocarcinomas and all of the 10
      metastatic colonic adenocarcinomas were immunostained. These results indicate
      that CDX2 is detectable in the majority of benign, borderline and malignant
      ovarian mucinous tumours and, therefore, makes this marker unsuitable when
      distinguishing primary from metastatic ovarian mucinous adenocarcinomas. However,
      CDX2 immunoreactivity could be useful in the distinction between endocervical and
      intestinal-type mucinous tumours of the ovary, which may have clinical relevance.

PMID- 14576941
TI  - Masked excitatory action of noradrenaline on rat islet beta-cells via activation
      of phospholipase C.
AB  - The effect of noradrenaline (NE) on rat islet beta-cells was examined. NE reduced
      insulin secretion from rat islets exposed to extracellular solutions containing
      glucose at 5.5 or 16.6 mM. In islets treated with pertussis toxin (PTX), however,
      NE increased insulin secretion. The NE-induced augmentation of insulin secretion
      was inhibited by prazosin. In intact islets, NE increased phospholipase C (PLC)
      activity, an effect that was prevented by treatment of islets with U-73122. NE
      elevated intracellular [Ca2+] ([Ca2+]i) in isolated beta-cells independently of
      PTX. Although this NE effect was inhibited by prazosin, phenylephrine did not
      mimic it. The [Ca2+]i response to NE was also prevented by the treatment of cells
      with U-73122. NE produced depolarization of beta-cells followed by nifedipine
      sensitive action potentials. NE reduced the whole-cell membrane currents through
      ATP-sensitive K+ channels (KATP), responsible for the depolarization. This NE
      effect was prevented by treatment of beta-cells with U-73122 or BAPTA/AM.
      Although at least some of our results imply the presence of alpha1-adrenoceptors,
      beta-cells were not stained by a polyclonal IgG antibody recognizing all
      adrenergic alpha1-receptor subtypes so far identified. These results suggest that
      an interaction of NE with an unknown type of receptor activates rat islet beta
      cells via a PLC-dependent signal pathway. This effect is, however, masked by the
      inhibitory action via a PTX-sensitive pathway also activated by NE.

PMID- 14576943
TI  - A one-step dual-labeling method for antigen detection in mast cells.
AB  - This paper describes a one-step light microscopy method for demonstrating the
      antigen contents of unequivocally identified mast cells. It is based on the
      differential metachromatic properties of proteoglycans, mostly heparin and
      chondroitin sulfate, and 1-naphthol in the presence of toluidine blue in an
      acidic medium. Proteoglycans occur in all mast cells and 1-naphthol is used to
      demonstrate the peroxidase activity of the sections treated by the horseradish
      peroxidase-labeled avidin-biotin complex method for antigen detection. Granules
      containing proteoglycans present the classical metachromatic reaction by
      appearing purplish-red, while granules containing antigen appear a brilliant
      green. When both types of granules are distinct inside the cell, single- and
      double-stained cells can be accurately separated and counted. We hope that this
      new procedure will contribute to a further identification of mast cell mediator
      contents and to a better understanding of the physiology of this cellular
      population.

PMID- 14576942
TI  - Decreased collagen type I/III ratio in patients with recurring hernia after
      implantation of alloplastic prostheses.
AB  - BACKGROUND: Abnormal collagen metabolism is suspected to play an important role
      in the pathogenesis of recurring inguinal and incisional hernias. Whereas
      alloplastic prostheses are nowadays routinely used, the quantity and quality of
      collagen formation after repair in humans has not been analysed in a large
      cohort. METHOD: Seventy-eight prostheses (Prolene, Atrium, Marlex, Vypro,
      Mersilene, Gore-Tex) implanted for inguinal and incisional hernia repair were
      explanted because of recurrence, chronic pain or infection. The mean implantation
      period was 17.9+/-11.2 (range 0.5-48) months. Collagen formation was investigated
      quantitatively (collagen-protein ratio) and qualitatively (collagen type I/III
      ratio). Results were related to clinical data that included gender, age,
      implantation period, indication for implantation/explantation, type and location
      of prosthesis. RESULTS: Mean collagen-protein ratio was 45.3+/-8.5 microg/mg,
      with significant differences between male (43.8+/-9.1 microg/mg) and female
      tissue samples (48.1+/-6.8 microg/mg, P=0.033). The mean collagen type I/III
      ratio of all samples investigated was 2.1+/-1.4. Samples explanted for recurring
      hernias exhibited a significantly decreased ratio (1.3+/-0.7, P<0.05) compared to
      samples explanted because of pain (3.4+/-1.2) or infection (2.9+/-1.6).
      Multivariate analysis excluded independent effects of age, gender, indication for
      implantation of prostheses, location and implantation period on collagen type
      I/III ratio. CONCLUSION: The present study confirms the importance of a
      biological approach, next to technical aspects, to the understanding of the
      pathogenesis of recurrent hernia formation and underscores the presence of a
      disturbed scarring process. The composition of scar tissue with a lowered
      collagen type I/III ratio and, therefore, reduced tensile strength may be a major
      contribution to hernia recurrence.

PMID- 14576944
TI  - Immunoelectron microscopic study for histamine in the gastric enterochromaffin
      like cells of rats treated with the proton pump inhibitor lansoprazole.
AB  - The enterochromaffin-like (ECL) cells of the gastric mucosa in animals play an
      important role in gastric acid secretion. They contain few granules and numerous
      secretory vesicles and microvesicles. They operate under the control of
      circulating gastrin. In the present study, we conducted an immunoelectron
      microscopic study for histamine (HA) in the ECL cells of rats given the proton
      pump inhibitor lansoprazole (LP), which is known to induce hypergastrinemia. The
      pre-embedding indirect immunoperoxidase procedure utilized a mouse monoclonal
      antibody AHA-2 against glutaraldehyde-conjugated HA. Rats received LP (50
      microg/kg per day, subcutaneously) over a period of a month, and developed
      hypertrophy of the ECL cells in the stomach. It was clearly demonstrated that HA
      was located to a much higher degree in the cytoplasm of ECL cells of LP-treated
      rats than in normal rats. HA immunoreactivity was observed in the cores of the
      granules and secretory vesicles of the ECL cells in all the rats, but in the LP
      treated rats it was observed in the cores of the newly developed vacuoles as
      well. These results may suggest that HA may be actively generated in the
      cytoplasm of the hypertrophic ECL cells of LP-treated rats. Also suggested in the
      present study is that HA is instrumental in the transformation of granules into
      secretory vesicles and in their consequent enlargement, and that vacuoles are
      formed by the fusion of large secretory vesicles. Furthermore, the finding that
      relatively little HA immunoreactivity existed in the vacuoles may suggest that
      the vacuoles actively degrade superfluous secretory products (for example, HA)
      through enhanced autophagocytosis and/or oxidative stress. Another possibility
      may be that the membrane-bounded structure regarded as the vacuoles in this study
      might actually be an invagination structure produced as a result of successive
      series of exocytosis through which the secretory vesicles actively and rapidly
      release HA.

PMID- 14576945
TI  - Increased levels of Helicobacter pylori IgG antibodies in aqueous humor of
      patients with primary open-angle and exfoliation glaucoma.
AB  - PURPOSE: A prospective, nonrandomized, comparative study was carried out to
      investigate the levels of anti- H. pylori-specific IgG antibodies in the aqueous
      humor and serum of patients with primary open-angle glaucoma (POAG) and patients
      with exfoliation glaucoma (XFG), and to compare them with those in age-matched
      cataract patients. METHODS: Aqueous humor was aspirated at the beginning of
      glaucoma surgery from 26 eyes of 26 patients with POAG, 27 eyes of 27 patients
      with XFG, and at the beginning of phakoemulsification cataract surgery from 31
      eyes of 31 age-matched normotensive cataract patients. Serum samples were
      obtained the day before surgery from all patients. Anti- H. pylori IgG
      concentration in the aqueous humor and serum was measured by means of an enzyme
      linked immunosorbent assay. RESULTS: The mean concentration (+/- SE) of anti- H.
      pylori-specific IgG was significantly greater in the aqueous humor samples from
      patients with POAG (14.27+/-3.86 U/ml) and XFG (14.25+/-3.39 U/ml) than in those
      from age-matched control cataract patients (4.67+/-1.07 U/ml); ( P=0.006 and
      P=0.003, respectively). No difference was observed in the levels of H. pylori
      specific IgG antibodies between POAG and XFG aqueous humor samples ( P=0.5).
      Similarly, the serum concentration of anti- H. pylori antibodies was
      significantly greater in patients with POAG (69.96+/-9.69 U/ml; P=0.013) and XFG
      (81.37+/-10.62 U/ml; P=0.002) than in the cataract controls (44.16+/-6.48 U/ml).
      The mean vertical cupping correlated significantly with the titer of anti- H.
      pylori-specific IgG in the aqueous humor in the POAG patients. CONCLUSION: H.
      pylori-specific IgG antibody levels are significantly increased in the aqueous
      humor and serum of patients with POAG and XFG. Moreover, the titer of anti- H.
      pylori antibody in the aqueous humor might reflect the severity of glaucomatous
      damage in POAG patients. These findings support a role for H. pylori infection in
      the pathobiology of these two common glaucomas.

PMID- 14576946
TI  - Histologic and immunohistochemical characterization of tumor and inflammatory
      infiltrates in oral squamous cell carcinomas treated with local multikine
      immunotherapy: the macrophage at the front line.
AB  - Squamous cell carcinomas of the head and neck (SCCHN) are excellent candidates
      for local immunotherapy owing to their accessibility and their infiltration by
      mononuclear cells that are susceptible to immunomodulation. A response rate of 25
      60% has been reported for treatment with natural IL-2 or a mixture of natural
      lymphokines. In the present study, biopsies and posttreatment excision specimens
      from nine patients with operable SCCHN treated systemically with a variety of
      immunomodulators and locally with natural lymphokines (multikine, CelSci) were
      analyzed in an attempt to correlate clinical response to histopathological and
      immunohistochemical changes. Formalin-fixed, paraffin-embedded tissues were
      stained with antibodies against lymphocytes (CD45, CD3, CD4, CD8, CD20),
      macrophages (CD68) including dendritic cells (S-100), markers for lymphocyte
      activation (CD30, HLA-DR), natural killer cells (CD56 and CD57), beta-2
      microglobulin and keratin. One patient showed a complete response to treatment
      and two a partial response. Tumor size was significantly smaller after therapy.
      Clinical and pathological regression were more prominent in the smaller tumors.
      Numerous macrophages, both mononucleated and multinucleated, were present along
      the tumor-stroma interface in the posttreatment specimens of seven patients, most
      prominently in the three patients with tumor regression. The increase in the
      number of CD68+ and S-100+ macrophages after treatment was statistically
      significant. Lymphocytic infiltrates, which showed some increase following
      treatment, were composed of a mixture of T and B lymphocytes, the former mostly
      in contact with the tumor and the latter placed more peripherally. CD8+
      lymphocytes extended into the tumors, whereas CD4+ lymphocytes showed minimal
      extension. Intensity of beta-2-microglobulin staining in tumors was significantly
      higher following therapy and associated with a better outcome. The marked
      increase in macrophages following treatment may indicate that the macrophage
      plays a major role in tumor recognition, destruction and clearance. An increase
      in the number of macrophages in a posttreatment specimen may indicate
      immunoresponsiveness.

PMID- 14576948
TI  - Bilateral high-frequency electrical impulses to the thalamus reduce voice tremor:
      acoustic and electroglottographic analysis. A case report.
AB  - An 81-year-old female patient suffering from disabling Holmes' tremor affecting
      both upper extremities, the head and additionally the vocal apparatus underwent
      bilateral thalamic ventralis intermedius nucleus (v.i.m.) stimulation. With the
      stimulation ON, the patient experienced complete suppression of the limb and head
      tremor and thorough voice normalization. Acoustic and electroglottographic (EGG)
      analysis showed a tendency towards hyperfunctional phonation with the stimulation
      ON as well as OFF, but a less disturbed vocal cord vibration pattern with the
      stimulation ON in comparison with a group of normal female speakers. This example
      shows that long-term monitoring of the vocal apparatus under deep brain
      stimulation therapy (DBS) of movement disorders must be planned in order to
      modify the stimulation parameters, if necessary, or to initiate logopaedic
      treatment.

PMID- 14576947
TI  - Frequent detection of Mycoplasma pneumoniae in Bell's palsy.
AB  - The cause of Bell's palsy (BP) remains unknown despite various hints to an
      infectious etiology. Mycoplasma pneumoniae is a common pathogen of the
      respiratory tract causing pharyngitis, tracheobronchitis or pneumonia.
      Neurological complications are the most frequent extrapulmonary manifestation. So
      far, only a few case reports suggested an association between cranial nerve palsy
      and M. pneumoniae infection. Patients with a BP who were admitted to the
      Department of Otorhinolaryngology or Neurology of the University of Wuerzburg
      between 2000 and 2002 were tested serologically for the presence of antibodies
      against Borrelia burgdorferi, herpes viruses (HSV-1/2, VZV) and M. pneumoniae.
      The diagnosis of mycoplasmal infection was made when at least one of the
      following criteria was met: a threefold rise or more in the titer of antibody of
      M. pneumoniae in paired sample or a microparticle agglutination assay (MAG) of >
      or =1:40 and the detection of IgA and/or IgM antibodies in the acute phase serum.
      Ninety-one consecutive patients could be included. Fifteen patients showed a
      reactivation of a VZV ( n=12) or of a HSV-1 ( n=3) infection. In six cases the
      immunoblot revealed specific antibody bands for B. burgdorferi. In 24 patients
      (26.4%) a seroconversion of M. pneumoniae could be detected. Only two patients
      complained of mild respiratory symptoms. According to our results, M. pneumoniae
      is frequently associated with Bell's palsy. Thus, a routine screening for this
      pathogen, even in the absence of respiratory symptoms, is necessary.

PMID- 14576949
TI  - A simple surgical technique for tracheoesophageal fistula closure.
AB  - Placement of a voice device in a tracheoesophageal fistula provides successful
      speech rehabilitation after total laryngectomy. However, in the long term,
      removal of the voice device and permanent closure of the fistula is sometimes
      necessary. This paper presents and evaluates a simple surgical technique for
      primary closure of tracheo-esophageal fistulae. We retrospectively review 12
      laryngectomees who received this technique of primary closure from 1997 to 2000.
      In 58% of the patients, permanent fistula closure could be obtained. Six patients
      (50%) healed primarily; in one patient (8%) the residual fistula opening healed
      secondarily. Four patients (33%) needed a second surgical procedure, and in one
      patient (8%) inserting a new speech prosthesis obliterated the residual fistula.
      Radiotherapy seems to compromise wound healing and therefore may be considered as
      a contraindication. Complications such as tracheal stenosis, tissue necrosis and
      pneumonia, etc., did not occur.

PMID- 14576950
TI  - Unilateral spontaneous dissection of the internal carotid artery presenting as
      hypoglossal nerve palsy.
AB  - A rare case of an isolated unilateral hypoglossal nerve palsy in a 61-year-old
      man is reported. Imaging showed a dissection of the extracranial internal carotid
      artery. The expansion of the circumference of the artery causes compression of
      the hypoglossal nerve resulting in a palsy. To the best of our knowledge this
      disorder has twice been dealt with in the otorhinolaryngological literature.

PMID- 14576952
TI  - Duration of the increase in amniotic fluid index (AFI) after acute maternal
      hydration.
AB  - The long-term effect of acute maternal hydration on amniotic fluid index (AFI)
      has not been previously studied. We evaluated the AFI of 25 pregnant women (ten
      women with normal AFI and 15 with decreased AFI) at 3, 24 and 48 h after maternal
      oral hydration with 2 l of water over 1 h. Post-hydration AFI at 3 h was
      significantly greater than pre-hydration AFI. However, AFI at 24 and 48 h were
      not significantly different from pre-hydration AFI. Maternal hydration increases
      AFI in women with normal and decreased amniotic fluid, but the increase in AFI
      lasts for less than 24 h.

PMID- 14576953
TI  - Premalignant lesions of the uterine cervix in a large cohort of Israeli Jewish
      women.
AB  - Israeli Jewish women are at low risk for cancer of the uterine cervix. In view of
      absent screening programs in Israel, there are only scarce data available with
      regard to results of PAP smears. The aim of this study was to assess the
      incidence of premalignant cervical lesions in the largest sample of PAP smears
      reported so far from Israel. We retrospectively analyzed the results of 297,849
      PAP smears, which had been examined in a single laboratory, during 9 years (1991
      1999). The incidence of low- and high-grade squamous intraepithelial was 0.69%
      and 0.29%, respectively. Our data indicate similar incidence rates for
      premalignant lesions in Jewish Israeli women as observed in Western countries,
      but no increase during the study period. In spite of relatively high incidence
      rates for premalignant lesions of the uterine cervix, the incidence rate for
      invasive cervical cancer remains conspicuously low. For unknown reason the
      conversion rate from premalignant cervical lesions to invasive cancer is lower in
      Israeli Jewish women than in European and North American women. We discuss
      possible reasons for this phenomenon and suggest that at this time mass screening
      for cervical cancer in Israel may probably not be justified.

PMID- 14576954
TI  - Assessment of TGF-beta1-mediated growth inhibition of HPV-16- and HPV-18
      transfected foreskin keratinocytes during and following immortalization.
AB  - The responsiveness to transforming growth factor-beta1 (TGF-beta1) of two human
      keratinocyte cell lineages (FK16A and FK18B) generated after transfection with
      HPV-16 and HPV-18, respectively, was investigated. Both cell lineages revealed
      loss of heterozygosity (LOH) at 18q and/or 3p associated with the acquisition of
      the immortal phenotype. These loci harbour genes (TGF-beta receptor II gene at
      3p, and Smad2 and Smad4 genes at 18q) encoding products involved in the TGF-beta1
      signalling pathway. Mortal and early immortal stages of both cell lineages
      displayed growth reduction upon exposure to TGF-beta1 concentrations in the range
      100 pg/ml to 1 ng/ml. However, the late immortal stages were resistant to TGF
      beta1 at concentrations up to 10 ng/ml. TGF-beta1 receptors type I and II were
      expressed at all stages in both cell lineages. Moreover, mRNA levels of Smad2 and
      Smad4 genes were nearly constant throughout. TGF-beta1 expression and secretion,
      which were demonstrated in all analysed stages, may provide selective conditions
      underlying unresponsiveness to TGF-beta1 upon prolonged monolayer culturing.
      Thus, LOH at 3p and/or 18q seen during HPV-mediated immortalization of human
      keratinocytes was not associated with resistance to TGF-beta1-mediated growth
      inhibition or a marked reduction in TGF- beta1 receptors and mRNA levels of Smad2
      or Smad4. Therefore, alternative events are likely to underlie unresponsiveness
      to TGF- beta1 in late-passage FK16A and FK18B cells.

PMID- 14576955
TI  - Hierarchy of evidence: differences in results between non-randomized studies and
      randomized trials in patients with femoral neck fractures.
AB  - INTRODUCTION: There have been a number of non-randomized studies comparing
      arthroplasty with internal fixation in patients with femoral neck fractures.
      However, there remains considerable debate about whether the results of non
      randomized studies are consistent with the results of randomized, controlled
      trials. Given the economic burden of hip fractures, it remains essential to
      identify therapies to improve outcomes; however, whether data from non-randomized
      studies of an intervention should be used to guide patient care remains unclear.
      We aimed to determine whether the pooled results of mortality and revision
      surgery among non-randomized studies were similar to those of randomized trials
      in studies comparing arthroplasty with internal fixation in patients with femoral
      neck fractures. MATERIALS AND METHODS: We conducted a Medline search from 1969 to
      June 2002, identifying both randomized and non-randomized studies comparing
      internal fixation with arthroplasty in patients with femoral neck fractures.
      Additional strategies to identify relevant articles included Cochrane database,
      SCISEARCH, textbooks, annual meeting programs, and content experts. We abstracted
      information on mortality and revision rates in each study and compared the pooled
      results between non-randomized and randomized studies. In addition, we explored
      potential reasons for dissimilar results between the two study designs. RESULTS:
      We identified 140 citations that addressed the general topic of comparison of
      arthroplasty and internal fixation for hip fracture. Of these, 27 studies met the
      eligibility criteria, 13 of which were non-randomized studies and 14 of which
      were randomized trials. Mortality data was available in all 13 non-randomized
      studies ( n=3108 patients) and in 12 randomized studies ( n=1767 patients). Non
      randomized studies overestimated the risk of mortality by 40% when compared with
      the results of randomized trials (relative risk 1.44 vs 1.04, respectively).
      Information on revision risk was available in 9 non-randomized studies ( n=2764
      patients) and all 14 randomized studies ( n=1901 patients). Both estimates from
      non-randomized and randomized studies revealed a significant reduction in the
      risk of revision surgery with arthroplasty compared with internal fixation
      (relative risk 0.38 vs 0.23, respectively). The reduction in the risk of revision
      surgery with arthroplasty compared with internal fixation was 62% for non
      randomized studies and 77% for randomized trials. Thus, non-randomized studies
      underestimated the relative benefit of arthroplasty by 19.5%. Non-randomized
      studies with point estimates of relative risk similar to the pooled estimate for
      randomized trials all controlled for patient age, gender, and fracture
      displacement in their comparisons of mortality. We were unable to identify
      reasons for differences in the revision rate results between the study designs.
      CONCLUSIONS: Similar to other reports in medical subspecialties, non-randomized
      studies provided results dissimilar to randomized trials of arthroplasty vs
      internal fixation for mortality and revision rates in patients with femoral neck
      fractures. Investigators should be aware of these discrepancies when evaluating
      the merits of alternative surgical interventions, especially when both randomized
      trials and non-randomized comparative studies are available.

PMID- 14576956
TI  - Does false aneurysm behave like a sarcoma? Distal femoral arterial false aneurysm
      simulated a malign mesenchymal tumor. A case report and review of the literature.
AB  - We report a case of a pseudo-aneurysm of the distal femoral artery presenting as
      a malignant mesenchymal tumor with insidious onset, progressive symptoms, large
      volume mass, and atypical radiological findings.

PMID- 14576957
TI  - Giant anterior sacral meningocele and posterior sagittal approach.
AB  - OBJECT: Anterior sacral meningocele (ASM) is a rare congenital malformation.
      Often while still asymptomatic, ASM may achieve a considerably size, to the
      extent of exerting a mass effect on the pelvic structures. Spontaneous rupture
      with subsequent septic meningitis is the most frequent and dangerous
      complication. The meningocelic sac is usually isolated by a surgical procedure
      that requires a sacral laminectomy or a transabdominal approach. Recently an
      alternative surgical technique, the posterior sagittal approach, has been
      proposed. METHODS: We report on a 15-year-old girl with a long clinical history
      of constipation and sporadic cystitis. Radiological examinations showed
      progressive enlargement of a presacral lipomeningocele, which grew to 12x14 cm. A
      posterior sagittal approach was performed; the stalk was ligated, the sac totally
      excised and a small associated tumour removed. No intra-/post-operative
      complications were observed. CONCLUSION: The posterior sagittal approach is an
      easy and safe surgical technique for the treatment of ASM, as it allows a
      complete isolation of the lesion and the removal of associated tumors without
      significant morbidity.

PMID- 14576958
TI  - Neurocutaneous melanosis.
AB  - BACKGROUND: Neurocutaneous melanosis (NCM) is a rare phakomatosis characterized
      by a focal or diffuse proliferation of melanin-producing cells in both the skin
      and the leptomeninges. This syndrome is believed to result from an error in the
      morphogenesis of embryonal neuroectoderm. FEATURES: Two-thirds of patients with
      NCM have giant congenital melanocytic nevi, and the remaining third have numerous
      lesions but no giant lesions. Most patients present neurological manifestations
      early in life, which can be secondary to intracranial hemorrhages, to impairment
      of cerebrospinal fluid circulation, and to malignant transformation of the
      melanocytes. PROGNOSIS: The prognosis of patients with symptomatic neurocutaneous
      melanosis is extremely poor, even in the absence of malignancy. Chemotherapy has
      been ineffective in the few patients in whom it has been tried.

PMID- 14576959
TI  - Androgen therapy in the aging male.
AB  - The world population is expanding rapidly; at the same time, life expectancy is
      increasing, and fertility rates are decreasing. Due to these facts, it is
      expected that the biggest increases of population growth will occur in the aging
      population. In the aging male, endocrine changes and a decline in endocrine
      function involve tissue responsiveness as well as reduced secretory output from
      peripheral glands and alterations in the central mechanism controlling the
      temporal organization of hormonal release. The latter are likely to be
      responsible for the dampened circadian hormonal and non-hormonal rhythms. These
      are in part responsible for the age-dependent decrease of the peripheral levels
      of testosterone, dehydroepiandrosterone (DHEA), the thyroid hormones, growth
      hormone (GH), IGF1 and melatonin. These hormonal changes, which develop in most
      men at about the age of 50, are in part responsible for endocrine deficiencies of
      some older men. One of the best-studied endocrine deficiencies is late-onset
      hypogonadism. This is a syndrome characterized by adverse effects on multiple
      organ systems and decreased quality of life, associated with advancing age and
      characterized by signs and symptoms of hypogonadism and a deficiency in serum
      androgen levels with or without a decreased genomic sensitivity to androgens. In
      cases of endocrine deficiencies, traditional endocrinology aims to replace the
      missing hormone or hormones with substitutes. It has been demonstrated that
      interventions such as hormone therapies may favorably influence some of the
      pathological conditions in aging men by preventing the preventable and delaying
      the inevitable. A comprehensive medical, psycho-social and life-style history, a
      physical examination and laboratory testing are essential for the diagnosis and
      management of late-onset hypogonadism. Acute, chronic or inter-current diseases
      must be taken into consideration prior to initiating any hormonal substitution
      therapy. In the era of evidence-based medicine, we have to acknowledge that data
      on testosterone therapy (HT) in the aging male is mostly circumstantial, based on
      experience in the treatment of transitional or chronic hypogonadism in young men
      resulting from disease or experiments of nature. However, over the past several
      years prospective studies on testosterone therapy in the aging male were
      performed and shown to be beneficial for certain older men in preventing or
      delaying some aspects of aging. Recommendations for algorithms for the diagnosis
      of late-onset hypogonadism and monitoring therapy for safety and efficacy are the
      subject of this paper.

PMID- 14576960
TI  - Fatigue stress fractures of the sacrum: diagnosis with MR imaging.
AB  - The aim of this study was to describe the MRI findings and clinical observations
      in a fatigue stress fracture of the sacrum. In this retrospective study, 380
      conscripts (53 women, 327 men; age range 18-29 years, mean age 20.7 years) who
      suffered from stress-related hip pain were studied with MRI of the pelvis. The
      findings of MRI were evaluated with regard to stress fracture of the sacrum.
      Thirty-one (8%) patients had MRI changes in signal intensity of the cranial part
      of the sacrum, extending to the first and second sacral foramina. The MRI changes
      in signal intensity were intermediate on T1-weighted images, and high on short
      tau inversion recovery or T2-weighted fat-suppressed images. A linear signal void
      fracture line was also seen. Multiple stress injuries to the pelvic bones were
      also seen in 7 of 31 (23%) patients. Five patients (16%) had bilateral sacral
      stress fracture. Fatigue sacral stress fractures appeared more commonly in women
      than in men ( p<0.001). During recovery time 20 of the 31 patients underwent
      control MRI, and fatty marrow conversion was seen in 8 (40%) cases as high signal
      intensity on T1-weighted images, which disappeared 5-6 months after the onset of
      symptoms. Fatigue sacral stress fractures are associated with stress-related hip
      pain. These fractures were more common in women than in men. Other stress
      injuries of the pelvis may be seen simultaneously with sacral stress fractures.
      Signal intensity of the sacrum was normal after 5-6 months.

PMID- 14576961
TI  - Functional disability and quality of life in patients with ankylosing
      spondylitis.

PMID- 14576963
TI  - Occupational risk for nephrolithiasis and bladder dysfunction in a chauffeur.
AB  - The occupational risks for nephrolithiasis have not been widely studied. The
      published literature focuses on exposure to heat stress and toxic substances, not
      on the equally important behavioral risk factor of limited water consumption over
      many years. Urologic morbidity has been associated with suppressing the need to
      drink or void under restrictive work environments; however, no such studies link
      work related behavioral change with the development of kidney stones. This case
      report is the first to associate a restrictive work environment with limited
      fluid consumption, resulting in the development of nephrolithiasis.

PMID- 14576965
TI  - Report of fogging effect on fast FLAIR magnetic resonance images of cerebral
      infarctions.
AB  - We report a case of multiple small, presumably iatrogenic, cortical infarctions
      detected incidentally on magnetic resonance imaging (MRI) 5 days after
      preoperative cerebral angiography but not apparent 12 days after the angiography
      on noncontrast MRI including a fast fluid-attenuated inversion recovery (FLAIR)
      sequence. However, the lesions showed marked contrast enhancement with gadolinium
      on postcontrast T1-weighted images. Cortical laminar necrosis was observed on MRI
      35 days after the initial angiographic study. This case shows that the MRI
      fogging effect may prevent detection of small cortical infarctions in the
      subacute stage even on fast FLAIR sequences. Postcontrast images should be
      studied to reduce diagnostic errors associated with this effect.

PMID- 14576966
TI  - Increase in dihydroxycarbamazepine serum levels in patients co-medicated with
      oxcarbazepine and lamotrigine.

PMID- 14576968
TI  - Always learning: continuing education for industrial chemists (and others, too!).

PMID- 14576967
TI  - A case of rhabdomyolysis with fatal outcome after a treatment with levofloxacin.
AB  - Fluoroquinolones are known to cause rhabdomyolysis. Levofloxacin is a recent
      fluoroquinolone and its muscular toxicity is not well documented. We describe the
      case of a 77-year-old female patient, who presented with an acute rhabdomyolysis
      after treatment with levofloxacin. She had a background of serious cardio
      pulmonary disease. She received an oral ambulatory treatment with levofloxacin
      for pulmonary infection. After 6 days, she presented with severe rhabdomyolysis,
      resulting in complete anuria with hyperkalaemia, complicated with acute liver
      cytolysis and respiratory failure. The treatment was a daily repeated
      haemodialysis. She presented with a fatal myocardial infarction 13 days after
      admission. The medical history inclines us to strongly suspect levofloxacin as
      the cause of this severe adverse drug reaction. We also reviewed 27 other suspect
      cases reported in the database provided by the World Health Organization
      Collaborating Centre for Drug Monitoring (Uppsala, Sweden). We conclude that
      rhabdomyolysis can be a rare, severe adverse effect of levofloxacin, as well as
      the other fluoroquinolones.

PMID- 14576969
TI  - Bioanalytical applications of Raman spectroscopy.

PMID- 14576970
TI  - Headspace solid-phase microextraction (HS-SPME): a microscale sampling technique
      for determination of monoterpene hydrocarbons in coniferous needles by gas
      chromatography/mass spectrometry (GC/MS).
AB  - A headspace solid-phase microextraction (HS-SPME) technique has been applied for
      the microscale sampling (single needle for Picea omorica, two needles of Picea
      abies) of volatile monoterpene hydrocarbons (MTHs) from conifer needles. A simple
      device consisting of a closed headspace vial equipped with an integral cutting
      device was used for the collection, homogenisation, and HS-SPME sampling. The
      highly sensitive gas chromatographic/mass spectrometric (GC/MS) analyses (LODs in
      tenths of ng g(-1) FW were obtained for 3xS/N criteria) of individual needles
      confirmed the space distribution of MTHs in different parts of a single sprout
      (base, centre, apex) and among the left, central and right sprout of a whorl. The
      highest concentrations of MTHs were found in the apical (leading) sprout (S) of a
      whorl. The serious increase of MTHs content near the base of the left (SNL)
      sprout and nearly zero concentrations in the central parts of both the side
      sprouts of P. abies corresponded to the morphology of the whorl. On the other
      hand, similar concentrations of MTHs were found in the apex of the side (SNL and
      SNR) sprouts. The distributions of MTHs obtained after HS-SPME and solvent
      extraction followed the similar trends for both species. HS-SPME is more suitable
      for the evaluation of distribution of volatiles in microscale experiments due to
      the more precise separation of needles into correct categories and elimination of
      "averaging" effects of the larger quantities of needles needed for the solvent
      extraction. The precision was improved by one order of magnitude due to the
      reduction of uncontrolled losses of volatile species during the sample treatment.

PMID- 14576971
TI  - Headspace SPME followed by GC/PFPD for the analysis of malodorous sulfur
      compounds in liquid industrial effluents.
AB  - Headspace SPME was used to analyse malodorous sulfur compounds in liquid
      industrial effluents. A pulsed flame photometric detector (PFPD) was selected for
      a specific and sensitive analysis. Two fibres, PDMS/Dvb and PDMS/Carboxen, which
      are particularly convenient for extracting small and volatile molecules were
      tested. To compare these fibres, both sensitivity and artefact formation were
      considered. The PDMS/Carboxen fibre showed the lower limits of detection and
      moreover the least artefact formation yields. It was therefore selected and
      headspace SPME extraction conditions were optimised. Limits of detection of the
      target compounds evaluated were 12-31 ng L(-1) and repeatability was around 7%.
      Due to the adsorption mechanism involved, extraction is strongly influenced by
      the sample matrix and the low affinity compounds can suffer displacement effects.
      To investigate the occurrence of this phenomenon, two sampling times
      corresponding to non-equilibrium (5 min) and equilibrium conditions (60 min) were
      investigated. An external calibration was carried out by using standard solutions
      for both sampling times. The developed procedure was then compared to the
      standard addition method on a real industrial effluent. The results obtained from
      the two methods and for the two extraction times were in good agreement,
      demonstrating that even a long sampling time can be used. Therefore, the simple
      and timesaving external calibration was defined as relevant for an accurate
      quantification of sulfur compounds by headspace SPME.

PMID- 14576973
TI  - Increased temporal patterns in choice responding and altered cognitive processes
      in schizophrenia and mania.
AB  - RATIONALE: The THEME method for measuring time-determined patterns (T-patterns)
      in behavior has been suggested as a new, more objective method for assessing
      cognitive disturbances in schizophrenia. OBJECTIVES: THEME was used to compare
      responses of schizophrenic patients with those having mood, schizoaffective, or
      severe anxiety disorders, and with healthy control subjects. METHODS: A two
      choice, button-pressing task was used to elicit T-patterns among responses, with
      knowledge-of-results (K) rewards and coin reinforcements (RF) as reinforcers.
      Subjects were compared by diagnosis, drug treatment, and gender. RESULTS:
      Schizophrenic and manic patients showed excessive numbers of, and more complex T
      patterns than controls. Schizophrenic and manic patients frequently demonstrated
      repetitive (stereotyped) responding, an effect never seen in healthy controls.
      Although clozapine (CLZ) reduced both excessive T-pattern structure and
      stereotyped responding, it also reduced growth of responding to the coin RF.
      CONCLUSIONS: Significant T-pattern increases may represent a common, time-related
      symptom of schizophrenia and mania. CLZ's effect on T-pattern production suggests
      that receptor effects other than the DAD(2) antagonism of "typical" neuroleptics'
      may be relevant to these findings.

PMID- 14576974
TI  - Di(2-ethylhexyl)phthalate (DEHP) metabolites in human urine and serum after a
      single oral dose of deuterium-labelled DEHP.
AB  - Human metabolism of di(2-ethylhexyl)phthalate (DEHP) was studied after a single
      oral dose of 48.1 mg to a male volunteer. To avoid interference by background
      exposure the D4-ring-labelled DEHP analogue was dosed. Excretion of three
      metabolites, mono(2-ethyl-5-hydroxyhexyl)phthalate (5OH-MEHP), mono(2-ethyl-5
      oxohexyl)phthalate (5oxo-MEHP) and mono(2-ethylhexyl)phthalate (MEHP), was
      monitored for 44 h in urine and for 8 h in serum. Peak concentrations of all
      metabolites were found in serum after 2 h and in urine after 2 h (MEHP) and after
      4 h (5OH-MEHP and 5oxo-MEHP). While the major metabolite in serum was MEHP, the
      major metabolite in urine was 5OH-MEHP, followed by 5oxo-MEHP and MEHP. Excretion
      in urine followed a multi-phase elimination model. After an absorption and
      distribution phase of 4 to 8 h, half-life times of excretion in the first
      elimination phase were approximately 2 h with slightly higher half-life times for
      5OH- and 5oxo-MEHP. Half-life times in the second phase-beginning 14 to 18 h post
      dose-were 5 h for MEHP and 10 h for 5OH-MEHP and 5oxo-MEHP. In the time window 36
      to 44 h, no decrease in excreted concentrations of 5OH- and 5oxo-MEHP was
      observed. In the first elimination phase (8 to 14 h post dose), mean excretion
      ratios of MEHP to 5oxo-MEHP and MEHP to 5OH-MEHP were 1 to 1.8 and 1 to 3.1. In
      the second elimination phase up to 24 h post dose mean excretion ratios of MEHP
      to 5oxo-MEHP to 5OH-MEHP were 1 to 5.0 to 9.3. The excretion ratio of 5OH-MEHP to
      5oxo-MEHP remained constant through time at 1.7 in the mean. After 44 h, 47% of
      the DEHP dose was excreted in urine, comprising MEHP (7.3%), 5OH-MEHP (24.7%) and
      5oxo-MEHP (14.9%).

PMID- 14576975
TI  - The tumorigenic characteristics of lime-piper betel quid-transformed JB6 cells.
AB  - Betel quid chewing is a general oral habit in Taiwan, India, southeastern Asian
      and South Africa with or without the additive of tobacco, alcohol or lime. In
      this study, the tumor-promoting neoplastic transformation effect of Lime-Piper
      betel quid (LPB) was examined on JB6 cells. The treatment of LPB at a high dose
      (1.0 mg/ml) for over 5 days or at lower doses (0.1, 0.5 mg/ml) for over 15 days
      induced the formation of transformed foci. The transformed cells showed the
      characteristics of colony formation in soft agar, higher growth rate and
      multilayer on culture dish. A two-fold induction of the protein levels of c-fos
      and c-jun proto-oncogenes was observed in the cells from the 50th passage
      (Cl1/p50, Cl2/p50 and Cl3/p50), suggesting that LPB-transformed cells were
      oncogenic. In addition, the LPB-transformed cells possessed an elevated level of
      c-Myc and an increased cell population distributed in the S phase of the cell
      cycle. These results demonstrated the promotion effect of LPB and indicate that
      it could be a tumor promoter.

PMID- 14576976
TI  - Purification and characterization of a lactonase from Erwinia cypripedii 314B
      that hydrolyzes ( S)-5-oxo-2-tetrahydrofurancarboxylic acid.
AB  - A bacterium, strain 314B, able to assimilate ( S)-5-oxo-2
      tetrahydrofurancarboxylic acid was isolated from soil and identified as Erwinia
      cypripedii. A lactonase hydrolyzing ( S)-5-oxo-2-tetrahydrofurancarboxylic acid
      to l-alpha-hydroxyglutaric acid was purified 63-fold with 2% recovery from crude
      extracts of this bacterium to homogeneity as judged by SDS-PAGE. The molecular
      masses estimated by SDS-PAGE and gel filtration were 41 kDa and 79 kDa,
      respectively. The maximum activity was observed at pH 6.5-7.5 and 35-45 degrees
      C. The enzyme showed lower activity toward dl-2-oxotetrahydrofuran-4,5
      dicarboxylic acid, but did not act on ( R)-5-oxo-2-tetrahydrofurancarboxylic acid
      and other natural and synthetic lactones tested.

PMID- 14576977
TI  - Diverse Mesorhizobium plurifarium populations native to Mexican soils.
AB  - Forty-six Mesorhizobium strains associated with the leguminous plants Leucaena
      leucocephala and Sesbania herbacea in an uncultivated Mexican field were
      characterized using a polyphasic approach. The strains were identified as
      Mesorhizobium plurifarium based upon the close relationships with the reference
      strains for this species in PCR-based restriction fragment length polymorphism
      analyses, sequencing of 16S rRNA genes, multilocus enzyme electrophoresis, and
      DNA-DNA hybridization. Although the strains isolated from both plants formed the
      same group in multilocus enzyme electrophoresis and cross-nodulations were
      observed in the laboratory, different electrophoretic types were obtained from
      the two plants grown in natural soils, indicating the existence of a preferable
      association between the plants and the rhizobia. The M. plurifarium strains from
      Mexico and the reference strains from Africa and Brazil formed different
      phenotypic clusters in a numerical taxonomy. The Mexican strains did not grow at
      37 degrees C and were sensitive to salty-alkaline conditions, while the reference
      strains from Africa and Brazil grew at 42 degrees C and were more resistant to
      salty-alkaline conditions. These results demonstrate that both the plants and
      environmental factors affected the evolution of rhizobia and that the Mexican
      strains had adapted to the neutral soils and the cool climate where they were
      isolated.

PMID- 14576979
TI  - A genome scan for loci linked to quantitative insulin traits in persons without
      diabetes: the Framingham Offspring Study.

PMID- 14576980
TI  - Processed meat intake and incidence of Type 2 diabetes in younger and middle-aged
      women.
AB  - AIM/HYPOTHESIS: The aim of this study was to investigate the association between
      processed and other meat intake and incidence of Type 2 diabetes in a large
      cohort of women. METHODS: Incident cases of Type 2 diabetes were identified
      during 8 years of follow-up in a prospective cohort study of 91246 U.S. women
      aged 26 to 46 years and being free of diabetes and other major chronic diseases
      at baseline in 1991. RESULTS: We identified 741 incident cases of confirmed Type
      2 diabetes during 716276 person-years of follow-up. The relative risk adjusted
      for potential non-dietary confounders was 1.91 (95% CI: 1.42-2.57) in women
      consuming processed meat five times or more a week compared with those consuming
      processed meat less than once a week ( p<0.001 for trend). Further adjustment for
      intakes of magnesium, cereal fibre, glycaemic index, and caffeine or for a
      Western dietary pattern did not appreciably change the results and associations
      remained strong after further adjustment for fatty acid and cholesterol intake.
      Frequent consumption of bacon, hot dogs, and sausage was each associated with an
      increased risk of diabetes. While total red meat (beef or lamb as main dish, pork
      as main dish, hamburger, beef, pork or lamb as sandwich or mixed dish) intake was
      associated with an increased risk of diabetes, this association was attenuated
      after adjustment for magnesium, cereal fiber, glycaemic index, and caffeine
      (relative risk: 1.44; 95% CI: 0.92-2.24). CONCLUSION/INTERPRETATION: Our data
      suggest that diets high in processed meats could increase the risk for developing
      Type 2 diabetes.

PMID- 14576981
TI  - Peroxisome proliferator-activated receptor gamma coactivator-1-dependent
      uncoupling protein-2 expression in pancreatic islets of rats: a novel pathway for
      neural control of insulin secretion.
AB  - AIMS/HYPOTHESIS: Sympathetic inputs inhibit insulin secretion through alpha2
      adrenergic receptors coupled with Gi protein. High adrenergic tonus generated by
      exposure of homeothermic animals to cold reduces insulin secretion. In this study
      we evaluate the participation of UCP-2 in cold-induced regulation of insulin
      secretion. METHODS: Static insulin secretion studies, western blotting and
      immunohistochemistry were used in this investigation. RESULTS: Exposure of rats
      to cold during 8 days promoted 60% ( n=15, p<0.05) reduction of basal serum
      insulin levels concentration accompanied by reduction of the area under insulin
      curve during i.p. GTT (50%, n=15, p<0.05). Isolated islets from cold-exposed rats
      secreted 57% ( n=6, p<0.05) less insulin following a glucose challenge. Previous
      sympathectomy, partially prevented the effect of cold exposure upon insulin
      secretion. Islets isolated from cold-exposed rats expressed 51% ( n=6, p<0.5)
      more UCP-2 than islets from control rats, while the inhibition of UCP-2
      expression by antisense oligonucleotide treatment partially restored insulin
      secretion of islets obtained from cold-exposed rats. Cold exposure also induced
      an increase of 69% ( n=6, p<0.05) in PGC-1 protein content in pancreatic islets.
      Inhibition of islet PGC-1 expression by antisense oligonucleotide abrogated cold
      induced UCP-2 expression and partially restored insulin secretion in islets
      exposed to cold. CONCLUSION/INTERPRETATION: Our data indicate that sympathetic
      tonus generated by exposure of rats to cold induces the expression of PGC-1,
      which participates in the control of UCP-2 expression in pancreatic islets.
      Increased UCP-2 expression under these conditions could reduce the beta-cell
      ATP/ADP ratio and negatively regulate insulin secretion.

PMID- 14576982
TI  - Effect of glycated LDL on microvascular tone in mice: a comparative study with
      LDL modified in vitro or isolated from diabetic patients.
AB  - AIMS/HYPOTHESIS: In vitro studies have suggested that glycation of LDL might be
      implicated in diabetic microangiopathy. We therefore investigated the in vivo
      effects of LDL glycated in vitro on the mouse skeletal muscle arteriolar tone.
      Since glycation naturally occurs during diabetes, we also tested the effects of
      LDL isolated from diabetic patients. METHODS: In anaesthetized mice, the
      spinotrapezius muscle microcirculation was observed, in situ, using the
      orthogonal polarization spectral imaging technology. The diameter of terminal
      (<20 microm) and small arterioles (20-40 microm) was measured before and after a
      bolus intravenous injection of glycated LDL followed by a continuous perfusion
      (115 micro g/kg/min). RESULTS: A slight decrease of terminal and small arterioles
      diameter (<10%) was observed with native LDL and LDL isolated from healthy
      subjects. In contrast, mildly glycated LDL induced a clear vasoconstriction of
      arterioles (>15%), which was further increased when highly glycated LDL was
      perfused (>22%). LDL isolated from diabetic patients mimicked the
      vasoconstriction obtained with in vitro mildly glycated LDL, which underwent
      similar glycation as those isolated from diabetic patients.
      CONCLUSION/INTERPRETATION: Our results show in vivo that acute perfusion of both
      types of glycated LDL (artificially or naturally modified), cause major
      microvascular modification by enhancing arteriolar tone in skeletal muscle. These
      findings highlight a new role of glycated LDL at the level of microvessels. We
      suggest that glycation of LDL could contribute to the impaired vascular
      reactivity observed in diabetes.

PMID- 14576983
TI  - Identification of differentially expressed genes in skeletal muscle of non
      diabetic insulin-resistant and insulin-sensitive Pima Indians by differential
      display PCR.
AB  - AIMS/HYPOTHESIS: Whole body insulin resistance results largely from impaired
      insulin-stimulated glucose disposal into skeletal muscle. We carried out muscle
      gene expression profiling to identify differentially expressed genes associated
      with insulin resistance. METHODS: Skeletal muscle total RNA samples from six
      pairs of non-diabetic insulin-resistant and insulin-sensitive Pima Indians
      matched for percent body fat were analyzed by DDPCR with 90 primer combinations.
      The mRNA expression concentrations of selected 13 known genes and four expressed
      sequences tags were measured by quantitative real-time RT-PCR in 50 non-diabetic
      Pima subjects. RESULTS: From over 6500 displayed DDPCR cDNA bands, 36 of the most
      differentially expressed cDNAs were identified, revealing 29 unique sequences: 16
      known genes, 10 expressed sequences tags and three unknown transcripts. Multiple
      regression analyses indicated that whole body insulin-mediated glucose disposal
      rates of the subjects, independent of age, sex, and percent body fat, were
      negatively correlated with mRNA concentrations of an EST (DD23; r=-0.38,
      p=0.007), ATP1A2 (r=-0.27, p=0.05), MAP2K4 (r=-0.34, p=0.02), and PRPSAP1 (r=
      0.37, p=0.008). Transcript concentrations of DD23 (r=0.27, p=0.05) and MTND4 (r=
      0.29, p=0.05) were correlated with plasma insulin concentration, independent of
      age, sex, and percent body fat. CONCLUSION/INTERPRETATION: Altered expression
      concentrations of these genes might be causes or consequences of insulin
      resistance, and these genes serve as candidate susceptibility genes for insulin
      resistance.

PMID- 14576984
TI  - Two loci on chromosome 5H determine low-temperature tolerance in a 'Nure'
      (winter) x 'Tremois' (spring) barley map.
AB  - Barley ( Hordeum vulgare subsp. vulgare) is an economically important diploid
      model for the Triticeae; and a better understanding of low-temperature tolerance
      mechanisms could significantly improve the yield of fall-sown cereals. We
      developed a new resource for genetic analysis of winter hardiness-related traits,
      the 'Nure' x 'Tremois' linkage map, based on a doubled-haploid population that is
      segregating for low-temperature tolerance and vernalization requirement. Three
      measures of low-temperature tolerance and one measure of vernalization
      requirement were used and, for all traits, QTLs were mapped on chromosome 5H. The
      vernalization response QTL coincides with previous reports at the Vrn-1/Fr1
      region of the Triticeae. We also found coincident QTLs at this position for all
      measures of low-temperature tolerance. Using Composite Interval Mapping, a second
      proximal set, of coincident QTLs for low-temperature tolerance, and the
      accumulation of two different COR proteins (COR14b and TMC-Ap3) was identified.
      The HvCBF4 locus, or another member of the CBF loci clustered in this region, is
      the candidate gene underlying this QTL. There is a CRT/DRE recognition site in
      the promoter of cor14b with which a CBF protein could interact. These results
      support the hypothesis that highly conserved regulatory factors, such as members
      of the CBF gene family, may regulate the stress responses of a wide range of
      plant species.

PMID- 14576985
TI  - Identification of quantitative trait loci involved in fruit quality traits in
      melon (Cucumis melo L.).
AB  - Two populations [an F(2) and a set of 77 double haploid lines (DHLs)] developed
      from a cross between a 'Piel de Sapo' cultivar (PS) and the exotic Korean
      accession PI 161375 were used to detect QTLs involved in melon fruit quality
      traits: earliness (EA), fruit shape (FS), fruit weight (FW) and sugar content
      (SSC); and loci involved in the colour traits: external colour (ECOL) and flesh
      colour (FC). High variation was found, showing transgressive segregations for all
      traits. The highest correlation among experiments was observed for FS and the
      lowest for FW and SSC. Correlations among traits within experiments were, in
      general, not significant. QTL analysis, performed by Composite Interval Mapping,
      allowed the detection of nine QTLs for EA, eight for FS, six for FW and five for
      SSC. Major QTLs ( R(2)>25%) were detected for all traits. QTLs for different
      traits were no clearly co-localised, suggesting low pleiotropic effects at QTLs.
      Sixty-one per cent of them were detected in two or more experiments. QTLs for FS
      were detected in more trials than QTLs for FW and SSC, confirming that FS is
      under highly hereditable polygenic control. ECOL segregated as yellow:green in
      both experimental populations. The genetic control of ECOL was found to be
      complex, probably involving more than two loci with epistatic interactions. One
      of these loci was mapped on linkage group 9, but the other loci could not be
      clearly resolved. FC segregated as white:green:orange. The locus responsible for
      the green FC was mapped on linkage group 1, and it was proposed to correspond to
      the previously described locus gf. The genetic control of orange FC was complex:
      two loci in linkage groups 2 and 12 were associated with orange flesh, but larger
      population sizes would be necessary to elucidate completely the genetic control
      of orange flesh in this cross. Exotic alleles from PI161375 showed beneficial
      effects on EA, FW and SSC, indicating the usefulness of PI 161375 as a new source
      of genetic variability to improve European and American cultivars.

PMID- 14576986
TI  - Micrococcus infection in patients receiving epoprostenol by continuous infusion.

PMID- 14576987
TI  - The role of apoptosis in childhood Henoch-Schonlein purpura.
AB  - The pathogenesis of vasculitis is complex and is yet to be fully elucidated,
      although it is known that inflammatory cells play a major role. Dysregulation of
      apoptosis and defective clearance of inflammatory cells could lead to the
      persistence of inflammation and excessive tissue injury. In this study we aimed
      to investigate Fas (CD95) and apoptosis on peripheral blood (PB) neutrophil and
      lymphocytes in Henoch-Schonlein purpura, both in the acute phase and after
      resolution to determine the role of apoptosis in this self-limited vasculitis.
      Leukocytoclastic vasculitis presenting with Henoch-Schonlein purpura (HSP) was
      diagnosed according to ACR 1990 criteria and confirmed by skin biopsy. Thirty
      seven patients (22 boys, 15 girls) aged 2.5-17 years (9 +/- 3.3) were enrolled in
      the study. Expression of CD95 and apoptosis were investigated by the annexin/PI
      method on peripheral blood neutrophils and lymphocytes in both the acute and the
      resolution phases of the disease. The mean neutrophil and lymphocyte CD95
      expression was 65.4 +/- 37.6% and 33.3 +/- 7.3%, respectively, in the acute stage
      and 62.8 +/- 44.2% and 41 +/- 20%, respectively, in the resolution ( P > 0.05).
      The percentage of apoptotic peripheral blood neutrophils and lymphocytes as
      determined by annexin positivity was 13.3 +/- 11.31% and 8.6 +/- 9.5%,
      respectively, during the acute phase and 4.6 +/- 3.4% and 3.1 +/- 3.1%,
      respectively, in the resolution (P = 0.002, P = 0.008). These results suggest
      that increased apoptotic process in the immune effector cells in the acute phase
      of the disease may play an important role in the early control of inflammatory
      response and repair in leukocytoclastic vasculitis, thereby contributing to the
      self-limited nature of the disease.

PMID- 14576988
TI  - Proteus mirabilis and rheumatoid arthritis: no association with the disease.
AB  - Proteus mirabilis (PM) is implicated in different studies in the pathogenesis of
      rheumatoid arthritis (RA) because of the structural homogeneity of its haemolysin
      B precursor with EQRRAA sequences in DRB 1 haplotype. The aim of the study was to
      compare the levels of antibodies specific to PM in the sera of patients with RA
      and healthy controls in our population. Serum samples from 78 consecutive RA
      patients and 75 healthy controls were analysed for the presence of IgG isotype
      and total immunoglobulins (IgG + IgA + IgM) against PM using enzyme-linked
      immunosorbent assay (ELISA) with two kinds of antigen preparations, whole
      bacteria and SDS-lysed bacterial extract. There was no significant increase in
      the concentrations of anti- Proteus antibodies (APA) in patients with RA compared
      to healthy controls in our population, when SDS-lysed bacterial extract or whole
      bacteria were used as antigen. The APA levels did not correlate with serum CRP
      levels. We conclude that P. mirabilis has no pathological or aggravating role in
      RA.

PMID- 14576989
TI  - Anti-C1q antibodies and antiendothelial cell antibodies in systemic lupus
      erythematosus - relationship with disease activity and renal involvement.
AB  - The aim of this study was to investigate the relationship between the presence
      and titre of antibodies against C1q (anti-C1q Ab) and disease activity and renal
      involvement in patients with systemic lupus erythematosus (SLE). Anti-C1q Ab were
      measured in 79 patients with SLE (70 women and 9 men; mean age 41.7 years; mean
      disease duration 8.4 years): 19 patients had active disease with lupus nephritis,
      8 active disease without nephritis, 26 inactive disease with nephritis and 26
      inactive disease without nephritis. Anti-dsDNA antibodies (EIA and
      immunofluorescence), antiendothelial cell antibodies (AECA) and complement levels
      (C3, C4, total haemolytic complement activity) were determined in parallel. Anti
      C1q Ab were positive in 49%, anti-dsDNA Ab in 61% and AECA in 19% of the
      patients, respectively. Significantly higher titres of anti-C1q Ab were found in
      patients with active disease compared with those with inactive SLE ( P < 0.01).
      Serum levels of anti-C1q Ab showed a positive correlation with anti-dsDNA Ab and
      SLEDAI score ( P < 0.01) and a negative correlation with C3 ( P < 0.05), C4 ( P <
      0.01) and CH50U ( P < 0.01). The presence of anti-C1q Ab was not different
      between patients with or without nephritis. In patients with ( P < 0.05) and
      without nephritis ( P < 0.01) the frequency of anti-C1q Ab was significantly
      higher in active patients compared with inactive patients. Both anti-C1q and anti
      ds-DNA Ab were detectable in 74% of patients with active nephritis but only in
      30% of all other patients ( P=0.001). None of the patients with active nephritis
      was negative for anti-C1q and anti-dsDNA Ab, whereas 37% of the patients without
      active nephritis were negative for both antibodies ( P < 0.01). Sensitivity,
      specificity, positive and negative predictive values for active lupus nephritis
      among SLE patients were 100%, 50%, 51.9% and 100% for anti-dsDNA Ab (EIA) and
      74%, 70%, 57% and 89.4% for positive findings of both anti-dsDNA and anti-C1q Ab.
      The presence and titre of anti-C1q-Ab in SLE are related to disease activity.
      Absence of anti-dsDNA Ab excludes active nephritis; positive findings of both
      anti-dsDNA Ab and anti-C1q Ab are of relatively high specificity for active
      nephritis.

PMID- 14576990
TI  - Raynaud's phenomenon: clinical spectrum of 118 patients.
AB  - OBJECTIVES: To establish the prevalence of the associated secondary diseases in
      patients with Raynaud's phenomenon (RP) attending a rheumatology specialty centre
      and to determine the frequency with which a secondary illness develops in those
      having RP, in absence of a well-defined secondary cause. METHODS: 118 consecutive
      patients were evaluated. Medical history, physical and laboratory investigations
      entered into a database. Patients with primary RP and patients with RP who did
      not fulfil any diagnostic criteria for inclusion in a secondary form were
      followed up over a three-year period. RESULTS: 63 RP patients were found with
      related conditions. 35 patients met criteria for inclusion in a primary RP group,
      20 patients had 'unclassifiable' RP, of which two (10%) developed a well-defined
      disease. None of the primary RP patients developed a secondary disease.
      CONCLUSIONS: This study shows that less than 50% of patients with RP attending a
      rheumatology specialty centre have a connective tissue disease. Patients with
      isolated RP appear to have a benign disease, since primary RP remains as such,
      and only a small percentage of patients with 'unclassifiable' RP evolve into a
      well-defined CTD.

PMID- 14576991
TI  - Avocado-soybean unsaponifiables (ASU) for osteoarthritis - a systematic review.
AB  - Patients suffering from osteoarthritis (OA) are often tempted to try
      'alternative' treatment options. Avocado/soybean unsaponifiables (ASU) have shown
      some promise for OA. This systematic review is aimed at critically evaluating the
      data from rigorous clinical trials of ASU. Six databases were searched for
      randomised, placebo-controlled, double-blind trials of ASU. Four studies could be
      included. Key data were extracted according to predefined criteria and tabulated
      as well as discussed in narrative form. The methodological quality of the four
      studies was high. They included patients with OA of the knee and hip. The dose of
      ASU was 300 mg/day and one trial also included a group treated with 600 mg/day.
      Three of the four trials suggested efficacy of ASU for improving the symptoms of
      OA. The majority of rigorous trial data available to date suggest that ASU is
      effective for the symptomatic treatment of OA and more research seems warranted.
      However, the only real long-term trial yielded a largely negative result.

PMID- 14576992
TI  - Inclusion body myositis in connective tissue disorders: case report and review of
      the literature.
AB  - We report a patient with systemic lupus erythematosus (SLE) and secondary
      Sjogren's syndrome (SS) who developed inclusion body myositis (IBM) which,
      contrary to the typical presentation of this disorder, was symmetrical in nature
      although the diagnosis was only made after electron microscopy was performed.
      Therapy with increased doses of methotrexate proved to be beneficial, with the
      patient having full recovery after 8 months of therapy. It appears that a subset
      of IBM may be related to autoimmune disorders, an issue that was disputed in the
      past, and these patients may have a better prognosis than typical IBM patients.
      This is the first case report of IBM in a patient who had the dual diagnosis of
      SLE and SS.

PMID- 14576993
TI  - Efficacy of imatinib mesylate (STI571) treatment for a patient with rheumatoid
      arthritis developing chronic myelogenous leukemia.
AB  - We report on an 80-year-old man with rheumatoid arthritis (RA) who presented with
      chronic myelogenous leukemia (CML). Five years after the onset of RA, the CML
      diagnosis was made. The patient was treated for CML with 300 mg of imatinib
      mesylate (STI; signal transduction inhibitor 571) for 8 weeks. Laboratory tests
      showed that the C-reactive protein level, percentage of cells exhibiting the
      Philadelphia chromosome (Ph1), WBC count, and Lansbury index for RA all dropped
      respectively from 7.5 mg/dl to 1.0 mg/dl, 74.9% to 1%, 25, 100/microl to
      9900/microl, and 51% to 14%. Administration of imatinib mesylate is felt to be
      effective in treating not only CML but also RA in the active stage.

PMID- 14576995
TI  - Thrombosis in systemic lupus erythematosus: effect of inherited thrombophilic
      mutations.
AB  - Thrombosis in the venous or arterial system is quite common in systemic lupus
      erythematosus (SLE). We describe a young female patient whose first presentation
      was in the form of deep venous thrombosis of the right lower extremity. Her
      family history for thrombosis was positive and further studies revealed her to
      have SLE. Genetic studies showed that she had thrombophilic mutations of factor
      V, prothrombin and methylene tetrahydrofolate reductase genes. Her therapeutic
      response to anticoagulant therapy was satisfactory. The presence of inherited
      thrombophilic mutations must be searched for in SLE patients with thrombosis,
      especially in cases with a positive family history.

PMID- 14576994
TI  - Eosinophilia and hyperimmunoglobulinemia E as the presenting manifestations of
      Wegener's granulomatosis.
AB  - Eosinophilia has long been known as a hallmark of Churg-Strauss syndrome but has
      rarely been reported in Wegener's granulomatosis (WG). Here we describe a patient
      with WG who had skin, kidney and lung involvement as well as striking peripheral
      eosinophilia and hyperimmunoglobulinaemia E (hyper-IgE). The patient's clinical
      picture was complicated by intra-alveolar haemorrhage resulting in severe anaemia
      and respiratory failure. The pulmonary symptoms recovered completely, but the
      renal involvement evolved into end-stage renal failure despite intensive
      immunosuppressive treatment, intravenous immunoglobulin and plasmapheresis. We
      suggest that the presence of eosinophilia and hyper-IgE might contribute to the
      development of different disease patterns in WG.

PMID- 14576996
TI  - Weber-Christian disease presenting with ocular manifestations.
AB  - A Japanese patient with Weber-Christian disease (WCD) presenting with ocular
      symptoms is reported. Panniculitis in the retrobulbar fat was diagnosed according
      to the histological findings from biopsy specimens, and improved over a month
      under steroid administration. Only three patients showing ocular manifestations
      have previously been reported. Panniculitis was in the late stage and a medium
      dose of prednisolone was effective in this patient. A biopsy of the orbital fat
      was useful for diagnosis. However, it is important to recognise that the stage of
      inflammation varies according to the fat tissue involved by WCD.

PMID- 14576997
TI  - Unusual causes of reactive arthritis: Leptospira and Coxiella burnetii.
AB  - Reactive arthritis is a well-defined clinical syndrome occurring after various
      infections, although most cases are usually associated with Chlamydiae and
      gastrointestinal pathogens. Its immunologic background has been extensively
      studied, as has its relationship with HLA-B27. We describe two cases of reactive
      arthritis arising after infections with two pathogens not so far related to the
      occurrence of reactive arthritis: one patient exhibited migratory oligoarthritis
      shortly after the course of acute Q fever, and another patient developed
      monoarthritis during recovery from leptospirosis. Arthritis was transient and did
      not exhibit a chronic course in either patient. We further discuss the context of
      pathophysiology of the arthritis in these patients, with an emphasis on the
      immunomodulatory properties of these two pathogens.

PMID- 14576998
TI  - Clinical features of septic arthritis at a tertiary teaching hospital in Lebanon.

PMID- 14577000
TI  - False dactylitis of the thumb.

PMID- 14576999
TI  - Rheumatoid arthritis in a patient with Asperger's syndrome and IDDM.

PMID- 14577001
TI  - Rheumatoid factor seropositivity and rheumatoid symptoms in coal worker's
      pneumoconiosis.

PMID- 14577003
TI  - Structural basis of the GM2 gangliosidosis B variant.
AB  - To study the structural basis of the GM2 gangliosidosis B variant, we constructed
      the three-dimensional structures of the human beta-hexosaminidase alpha-subunit
      and the heterodimer of the alpha- and beta-subunits, Hex A, by homology modeling.
      The alpha-subunit is composed of two domains, domains I and II. Nine mutant
      models due to specific missense mutations were constructed as well and compared
      with the wild type to determine structural defects. These nine mutations were
      divided into five groups according to structural defects. R178H is deduced to
      affect the active site directly, because R178 is important for binding to the
      substrate. C458Y and W420C are predicted to cause drastic structural changes in
      the barrel structure carrying the active site pocket. R504C/H is deduced to
      introduce a disruption of an essential binding with D494 in the beta-subunit for
      dimerization. R499C/H, located in an extra-helix, is deduced to disrupt hydrogen
      bonds with domain I and the barrel. R170W and L484P are deduced to affect the
      interface between domains I and II, causing destabilization. The structural
      defects reflect the biochemical abnormalities of the disease.

PMID- 14577002
TI  - Mutations in the gene encoding KIAA1199 protein, an inner-ear protein expressed
      in Deiters' cells and the fibrocytes, as the cause of nonsyndromic hearing loss.
AB  - We report three possibly disease-causing point mutations in one of the inner-ear
      specific genes, KIAA1199. We identified an R187C mutation in one family, an R187H
      mutation in two unrelated families, and an H783Y mutation in one sporadic case of
      nonsyndromic hearing loss. In situ hybridization indicated that the murine
      homolog of KIAA1199 mRNA is expressed specifically in Deiters' cells in the organ
      of Corti at postnatal day zero (P n) P0 before the onset of hearing, but
      expression in those cells disappears by day P7. The signal of KIAA1199 was also
      observed in fibrocytes of the spiral ligament and the spiral limbus through to
      P21, when the murine cochlea matures. Thus, the gene product may be involved in
      uptake of potassium ions or trophic factors with a particular role in auditory
      development. Although the R187C and R187H mutations did not appear to affect
      subcellular localization of the gene product in vitro, the H783Y mutation did
      present an unusual cytoplasmic distribution pattern that could underlie the
      molecular mechanism of hearing impairment. Our data bring attention to a novel
      candidate for hearing loss and indicate that screening of mutations in inner-ear
      specific genes is likely to be an efficient approach to finding genetic elements
      responsible for deafness.

PMID- 14577005
TI  - Mild head injury - mortality and complication rate: meta-analysis of findings in
      a systematic literature review.
AB  - BACKGROUND: Whether the strategy for care of mild head injury should be in
      hospital observation or computed tomography (CT) investigation and home care has
      been discussed lately. A necessary requirement for guidelines and the design of
      clinical trials would be knowledge about the risks of the condition. These have
      not been reliably summarised. The study aims to estimate as accurately as
      possible the mortality, the complication rates, and the frequency of pathological
      findings on CT in patients with mild head injury. METHODS: Mild head injury was
      defined as head trauma involving loss of consciousness or amnesia, but where
      neurological findings on arrival at hospital are normal (GCS 15). Large databases
      were searched to find relevant scientific literature, and the retrieved studies
      were critically appraised. Findings were used from all representative patient
      data sets that met predefined standards for minimum quality. Meta-analysis using
      the random-effects model was performed on the data collected. FINDINGS: The
      search yielded 24 studies on 24249 patients fulfilling the requirements. The mean
      mortality of patients was low, 0.1% (CI 0.05-0.15). Complications, mostly
      requiring surgery, occurred in 0.9% (CI 0.6-1.2) of the cases. In approximately
      8% (CI 6.1-9.5), pathological CT findings, dominated by haemorrhages, were
      identified in the acute phase. CONCLUSIONS: Of 1000 patients arriving at hospital
      with mild head injury, 1 will die, 9 will require surgery or other intervention,
      and about 80 will show pathological findings on CT. At least these 8% of patients
      will probably need in-hospital care.

PMID- 14577006
TI  - Role of brain natriuretic peptide in cerebral vasospasm.
AB  - BACKGROUND: Brain natriuretic peptide (BNP) is a potent natriuretic factor
      responsible for hyponatremia observed in patients with SAH. Through its systemic
      effects (reduction of blood volume and blood pressure) BNP may augment cerebral
      blood flow reduction and ischemia secondary to vasospasm. The purpose of the
      present study was to evaluate the relationship between BNP plasma concentration
      during the first 12 days following SAH and the development of cerebral vasospasm
      (CVS). The authors propose a hypothesis for the role played by natriuretic
      peptides in the pathophysiology of cerebral vasospasm based on the present
      findings and review the literature. METHODS: Thirty eight patients with
      spontaneous SAH were prospectively included in the present study. BNP plasma
      concentrations were assessed at four different time periods following SAH (day 1
      3, 4-6, 7-9, 10-12). TCD evidence of CVS was found in 26 patients (68.5%),
      fourteen patients (36.8%) had delayed ischemic neurological deficits (DIND).
      FINDINGS: Initial BNP plasma concentrations were significantly more elevated in
      patients who eventually did not develop DIND (95.07+/-107.65 pg/ml vs. 25.81+/
      22.57 pg/ml, p=0.0053). However, in patients with DIND, the BNP plasma
      concentration increased by 3.69 ( p<0.05), 5.89 ( p<0.001) and 4.54 fold (
      p<0.001) between days 1-3 to days 4-6, 7-9 and 10-12 respectively (day 1 was
      regarded as the day of hemorrhage). In patients without CVS or asymptomatic CVS
      the BNP plasma concentration decreased between days 1-3 to day 10-12. A similar
      trend in BNP plasma concentration was found in patients with severe SAH (Fisher's
      score 3-4) as compared with patients with non visible or moderate SAH (BNP
      concentration ratio day 7-9/1-3: 4.37 vs. 0.75, p=0.015; day 10-12/1-3: 3.37 vs.
      0.3, p=0.0144). The trend in BNP plasma concentration between day 1-3 to day 7-9
      was found to correlate with CVS severity with an average increase of 2.01, 3.8
      and 5.44 fold for mild, moderate and severe VS respectively ( p<0.01, r=0.4174).
      INTERPRETATION: These results suggest that BNP secretion in SAH patients is
      closely related to the bleeding intensity and vasospasm severity as well as to
      development of DIND with a progressive and marked increase during the clinical
      course in patients who eventually develop cerebral ischemia. Taken together the
      local and systemic effects of BNP on CBF suggest that BNP might play a role in
      the pathophysiology of CVS through its systemic effects on blood pressure and
      plasma volume BNP leading to an aggravation of brain ischemia secondary to
      vasospasm.

PMID- 14577007
TI  - Difference in configuration of ruptured and unruptured intracranial aneurysms
      determined by biplanar digital subtraction angiography.
AB  - There is an ongoing discussion about the risk of bleeding from unruptured
      intracranial aneurysms. Management guidelines were developed recently and some of
      the recommendations for decision making are based on the anatomical configuration
      of the aneurysm. The common assumption is that the presence of multiple lobes or
      a daughter sac indicates a higher risk of rupture. We have investigated the
      anatomical configuration of ruptured and unruptured intracranial aneurysms using
      biplanar digital subtraction angiography (DSA). The objective was to determine,
      whether there was a difference between ruptured and unruptured aneurysms
      regarding lobulation, the presence of a daughter sac or the shape as measured by
      the height/neck ratio. Biplanar DSA images of 124 patients were retrospectively
      analyzed. A total of 53 unruptured and 94 ruptured aneurysms were found (=147
      aneurysms in total). Aneurysms of less than 10 mm diameter accounted for 82% of
      all aneurysms. Overall, 10% of unruptured aneurysm showed a multilobular
      appearance on DSA compared with 20% of ruptured aneurysms (Fisher's exact test,
      p=0.10). In the 5-9 mm aneurysm group, multiple lobes were found significantly
      more frequent in ruptured aneurysms (26% vs. 4%, Fisher's exact test, p<0.05). A
      height/neck ratio of less than 1.5 was not found in unruptured aneurysms (0/26)
      but in 21% (12/57) of ruptured aneurysms (p<0.05). Our data provide scientific
      support for using morphological features for the decision making process in the
      management of unruptured intracranial aneurysms. An irregular multilobar
      appearance was significantly more common in aneurysms of 5-9 mm size that
      ruptured.

PMID- 14577008
TI  - Neuropsychological assessment after microsurgical clipping or endovascular
      treatment for anterior communicating artery aneurysm.
AB  - BACKGROUND: After open surgery for ruptured ACoA aneurysms, several patients who
      have achieved a favourable neurological outcome still exhibit significant
      cognitive deficits. The aim of this study was to investigate the cognitive
      performances in patients with ACoA aneurysms submitted to different therapeutic
      options such as endovascular treatment and surgical clipping. METHODS: We
      evaluated 37 consecutive patients in WFNS grade I or II, who underwent an early
      treatment (within 48 hours) of a bleeding ACoA aneurysm: 20 out of 37 were
      surgically clipped (group A) and 17 were treated with endovascular coiling (group
      B). These two groups were compared with 16 patients (group C) with subarachnoid
      haemorrhage and negative cerebral panangiography and with 18 volunteers (group D)
      without neurological or psychiatric disorders. All patients were neurologically
      intact at discharge and were in Glasgow Outcome Scale 1 at 6 months follow-up
      after SAH. All subjects were tested to assess selective attention, verbal,
      spatial and logical memory, frontal lobe executive functions, language and
      intelligence. Depressive symptoms and anxiety were also examined. FINDINGS:
      Selective attention, verbal and spatial memory, and intelligence tests didn't
      show any significant difference between the patients and the controls. Surgically
      treated patients showed a significant worse performance on the logical memory and
      on the frontal lobe executive functions compared to controls, while the
      endovascular group and the group C (not treated) showed a significant decrease
      only in the literal fluency score.Moreover, the surgical group showed a
      significant impairment in using grammatical and syntactical rules to produce
      sentences. No significant difference was found between the group B, C and
      controls. Treated patients were not significantly more depressive or anxious than
      controls. INTERPRETATION: Investigation of neuropsychological deficits can show
      an impairment, even in patients classified as good outcome by Glasgow Outcome
      Scale (GOS). The frontal lobe functions and language are impaired especially in
      surgically treated in comparison with controls, but no significant difference was
      found respect to the endovascular and no treated patients (group C).

PMID- 14577009
TI  - Results and outcome of neurosurgical treatment for extradural metastases in the
      cervical spine.
AB  - Metastatic lesions are the most common spinal extradural tumours. Significant
      advances in their neurosurgical management have been made in the last two
      decades. This retrospective study was undertaken to summarise the long-term
      results of surgery and the outcome of patients with cervical spine metastases.
      Sixty-two patients with cervical spine metastases who underwent instrumented
      spinal surgery at a single centre in an 12-year period (1989-2000) were analysed.
      All patients presented with local pain and with either neurological deficits,
      spinal instability, or a combination of both. A standard anterior approach to the
      cervical spine was chosen, and a partial or total vertebrectomy and vertebral
      body replacement with subsequent anterior instrumented fusion were carried out in
      all cases. General and neurological status was evaluated at baseline and in
      regular intervals thereafter. Plain X-rays, CT, and MRI were used for
      preoperative planning. Postoperative follow-up was done by X-rays. The mean
      follow-up time for all patients was 1.5 years. A stable bony fusion of the
      cervical spine was achieved in 60 patients (96.8%), with two additional patients
      needing a further procedure for maintaining the mechanical stability of the
      spine. There was mild early surgery-related morbidity, and no mortality. The most
      frequent temporary surgery-related side effect was reversible vocal cord paresis
      in 5 cases (8.0%). There were 3 cases (4.8%) of early instrumentation failure.
      One of these was symptomatic and underwent second-look surgery. No late
      complications occurred due to instrumentation hardware failure. The 1-year
      survival rate of all patients after surgery was 58%, and the 2-year survival rate
      was 21%. Our results demonstrate that surgical removal of extradural metastases
      with subsequent instrumented fusion is a low-morbidity and low-complications
      procedure with high rates of permanent stabilisation of the compromised cervical
      spine. In addition, it improves the neurological deficits and relieves the local
      pain in a significant proportion of patients. Excellent local control of
      malignant disease can be achieved by the surgical procedure aided by subsequent
      local and systemic adjuvant therapy. Overall survival time and prognosis of the
      patients, however, are mainly depending on the type and the stage of the primary
      malignancy.

PMID- 14577010
TI  - Gamma knife radiosurgical management of petroclival meningiomas results and
      indications.
AB  - BACKGROUND: Surgical treatment of petroclival meningiomas remains challenging. In
      order to refine indications for the use of stereotactic radiosurgery in the
      treatment of these tumours, we retrospectively evaluated our experience in this
      field. METHODS: Thirty-two patients harboring a petroclival meningioma were
      treated consecutively using a Gamma knife between December 92 and June 1998.
      Eight patients underwent radiosurgery after one or more attempted surgical
      removals and 24 had radiosurgery as the primary treatment. The main symptoms
      before radiosurgery were cranial nerve palsies, including a sixth nerve deficit
      in 10 patients and a trigeminal nerve disturbance in 9. All patients underwent a
      conformal multi-isocentric treatment (mean isocenter's number 8.8) and the dose
      delivered at the tumour margin ranged from 10 to 15 Gy (mean dose 13 Gy).
      FINDINGS: The duration of follow-up varied from 24 to 118 months (mean clinical
      follow-up 56 months, mean radiological follow-up 52.6 months). All 32 patients
      survived. The tumour volume remained unchanged in 28 patients and decreased
      slightly in 4. Neurological status worsened permanently in 2 patients with a
      delayed hemiparesis due to focal pontine infarction. These complications were
      associated with large meningiomas with vascular involvement and ventral brainstem
      compression, and occurred at the very early stage of our experience. At last
      follow-up, preoperative fifth or sixth cranial nerve deficits had improved or
      recovered in 13 out of 19 patients and any delayed worsening or new cranial nerve
      deficits were not observed after radiosurgery. CONCLUSIONS: Stereotactic
      radiosurgery with a Gamma knife provides effective management of small to middle
      sized petroclival meningiomas and is an alternative to microsurgery. Careful
      selection of patients and use of major technical refinements should improve the
      safety of this treatment.

PMID- 14577011
TI  - Clinical evaluation of stereotactic brain biopsies with an MKM-mounted instrument
      holder.
AB  - OBJECT: The aim of this study was to assess the clinical usefulness and accuracy
      of robot-assisted frameless stereotactic brain biopsies with a recently
      introduced MKM-mounted instrument holder. METHODS: Twenty-three patients with
      intracranial lesions participated in this study. Depending on the size of the
      intracranial lesion, fiducials for image-to-patient co-ordinate transformation
      consisted either of bone screws or adhesive markers. Shortly after surgery,
      postoperative MRI-imaging was performed to demonstrate the location of the biopsy
      site. These images were compared with the preoperative images to assess the
      biopsy localisation error. RESULTS: Postoperative biopsy sites could be
      demonstrated in six patients with bone screws and in 14 with adhesive markers.
      These two subgroups yielded average biopsy localisation errors of 3.3 mm (SD 1.7
      mm) and 4.5 mm (SD 2.0 mm) respectively. This difference was not statistically
      significant. One biopsy was located in a liquefied haematoma. All others yielded
      pathological tissue. There were two postoperative haemorrhages, of which only one
      was temporarily symptomatic. There was no mortality in the first 30 days after
      surgery. CONCLUSIONS: Robot-assisted frameless point-stereotactic techniques
      represent an alternative to frame-based techniques for the performance of
      stereotactic biopsies.

PMID- 14577012
TI  - Ethylene oxide sterilization of autologous bone flaps following decompressive
      craniectomy.
AB  - INTRODUCTION: In patients undergoing decompressive craniectomy, the bone flap is
      temporarily preserved either in the subcutaneous tissue of the patient or frozen.
      However, there are some drawbacks related to these methods. MATERIAL AND METHODS:
      In 16 patients in whom the bone flap was removed for decompressive craniectomy,
      the bone was firstly washed in hydrogen peroxide and then placed in hermetically
      sealed bags and sterilized using ethylene oxide. The bone was repositioned after
      an average period of 4.3 months. RESULTS: One patient sustained an infection of
      the surgical wound which required permanent exclusion of the bone flap. In all
      the others, esthetic and functional results were good after an average follow-up
      of 20 months. Control CT-scan of the bone flap demonstrated preservation of its
      structural features with fusion of the bone margins and revitalization of the
      flap. On MRI a subdural space was again visible. CONCLUSIONS: Sterilization of
      the bone flap with ethylene oxide in patients undergoing decompressive
      craniectomy avoids some of the drawbacks related to the techniques currently
      used. The easiness, low cost, good aesthetic and functional results of this
      procedure make it a valid alternative to other techniques for preservation of
      autologous bone in decompressive craniectomies.

PMID- 14577013
TI  - Epidermoid cysts of the fourth ventricle: very long follow up in 9 cases and
      review of the literature.
AB  - This study reports late surgical results obtained in 9 patients operated on for
      an epidermoid cyst of the fourth ventricle. They represent 19/9% of all cases of
      epidermoids treated at our Department over a period of 25 years (1975-2000). 7
      cases were diagnosed with CT and 2 cases with MR. Duration of clinical history
      ranged from 2 months to 6 years (mean: 2,2 years). Preoperatively, 2 cases
      presented spontaneous remission of neurological symptoms and signs lasting about
      1 year. 7 (77,8%) patients underwent subtotal removal of the cyst whereas in 2
      patients the lesion was totally excised. 3 patients (33,3%) underwent a second
      operation for symptomatic recurrence diagnosed between 10 and 17 years from the
      first operation. At present, 7 (77,8%) patients are alive (mean follow up of 14,5
      years, ranging from 5 to 23 years) without neuroradiological and clinical
      evidence of tumour recurrence. In this group, 6 have no neurological problems and
      1 suffers from a light vestibulo-cerebellar syndrome. Fourth ventricle
      epidermoids have a good long-term prognosis even in the case of only subtotal
      removal. Follow-up clinical and MR controls allow an earlier diagnosis of
      recurrence. Surgery of recurrent cysts can be more demanding; nonetheless, long
      term prognosis can be quite good for patients in well preserved neurological
      condition.

PMID- 14577014
TI  - Extra-axial subarachnoid ependymoma of the cerebral convexity.
AB  - A 29-year-old man had two episodes of seizures in 9 months. Following the first
      seizure he developed hemiparesis, which gradually progressed. Investigations
      revealed a large cerebral convexity mass lesion simulating a meningioma. During
      operation, a reddish-brown and well-defined tumor located in the subarachnoid
      space was encountered. Histopathological examination revealed a typical
      ependymoma. Extra-axial cerebral convexity ependymomas are extremely rare. The
      case is reported and a brief review of six similar cases reported in the
      literature is undertaken.

PMID- 14577015
TI  - Salmonella enteritidis causing brain abscess and coxitis following intracranial
      surgery.
AB  - We report the case of a 46-year-old woman who underwent surgery for an
      adamantinous craniopharyngeoma (WHO grade I). The postoperative course, during
      which the patient received 16 mg/day of dexamethasone, was initially uneventful.
      After a fortnight the patient developed infectious signs and an intracranial
      abscess at the operation site with simultaneous purulent coxitis. Both the
      intracranial abscess and the coxitis were evacuated and drained. In tissue
      samples and pus obtained during re-craniotomy and during surgery on the hip,
      Salmonella enteritidis was detected by cultivation. Salmonella enteritidis was
      also isolated from several stool specimens. There was no known salmonellosis in
      the patient's medical history. She recovered as a result of antibiotic treatment
      with ciprofloxacin and chloramphenicol. The intracranial abscess healed without
      leaving any neurological deficit. Unfortunately the left hip subsequently
      required further surgery, culminating in removal of the entire femoral head.
      Prosthetic replacement could not yet be performed due to the recurrent septic
      course of the hip. Our case illustrates a serious complication with presumed
      haematogenous spread of the infection from a pre-existing asymptomatic and
      unknown colon infection. The immunosuppressive effect of corticosteroids in the
      treatment of the brain neoplasm might have been a contributing factor to the
      sudden exacerbation of the latent infection.

PMID- 14577016
TI  - A case of germinoma in the septum pellucidum manifesting as amnesia and
      hemiparesis.
AB  - BACKGROUND: We report a rare case of germinoma mainly located in the septum
      pellucidum. CASE DESCRIPTION: A 19-year-old man presented with germinoma located
      in the septum pellucidum manifesting as amnesia and right hemiparesis. Magnetic
      resonance imaging demonstrated a heterogeneously enhanced mass in the septum
      pellucidum and abnormal T2-weighted signals in the left basal ganglia. An
      anterior transcallosal approach was performed to remove the mass in the septum
      pellucidum. The histological diagnosis was germinoma. Radiotherapy and
      chemotherapy were given. He was discharged with slight amnesia and right
      hemipareis. INTERPRETATION: Intracranial germinoma can arise from the septum
      pellucidum.

PMID- 14577017
TI  - Simple bone cyst occurring in calvarium.
AB  - A 60 year-old female presented with a non-specific headache that she had
      experienced for 4 years. A simple skull X-ray indicated a well-defined, lobulated
      and radiolucent lesion with a thin sclerotic rim involving the parietal bone
      (Fig. 1A). Computed tomography revealed a hypodense lesion. Magnetic resonance
      imaging showed a 2 cm-sized cystic lesion in the diploic space with both tabular
      involvement. This lesion was not enhanced by contrast agent. It was well defined
      and the periosteum was intact. The cyst paralleled the CSF in signal intensity on
      all pulse sequences. No fluid levels were detected (Fig. 1B, C, D). After the
      scalp was incised, a semi-translucent and light yellow- to white-coloured bony
      lesion was easily identified. The outer bony cortex of this lesion was slightly
      elevated, and the consistency was same as that of the normal skull. A craniectomy
      was performed and the cystic skull lesion was removed. The inner surface of this
      cystic lesion was intact but appeared irregular. The cystic cavity was empty and
      the dura did not appear to be involved. Histologically, it was a simple cystic
      cavity without lining epithelium, and the surrounding bony structures were normal
      (Fig. 1E, F). It was diagnosed as a simple bone cyst (SBC). The postoperative
      course was uneventful.

PMID- 14577019
TI  - Oral morphine and respiratory function amongst hospice inpatients with advanced
      cancer.
AB  - BACKGROUND: Respiratory depression is the opioid adverse effect feared most by
      physicians. This may hinder adequate dosing in cancer pain. The study was
      conducted to examine the respiratory function of patients with advanced cancer
      receiving significant doses (>100 mg/24 h) of oral morphine. PATIENTS AND
      METHODS: Consecutive pain-free hospice inpatients with advanced cancer receiving
      high-dose immediate-release oral morphine were evaluated. A single assessment of
      respiratory rate (RR), arterial blood gas (ABG), and peak flow rate (PFR) was
      made at assumed morphine steady state. Venous blood was drawn for a trough
      morphine plasma level. RESULTS: Of 31 patients who consented to examination, 20
      completed the study assessment; 12 had chronic bronchitis. The median morphine
      dose was 30 mg 4-hourly (range 20 to 90 mg). Only one patient had evidence of
      ventilatory impairment. CONCLUSIONS: Morphine does not commonly cause chronic
      ventilatory impairment when given in this way in this population even in the
      presence of pre-existing or concurrent respiratory disease. Oral morphine given
      repeatedly in individualized dosage is a safe and efficacious analgesic in the
      majority of those with advanced cancer.

PMID- 14577020
TI  - Utilization of palliative radiotherapy for breast cancer patients with bone
      metastases treated with bisphosphonates-Toronto Sunnybrook Regional Cancer Centre
      experience.
AB  - BACKGROUND: The use of both bisphosphonates and palliative radiotherapy for the
      prevention and treatment of skeletal complications in women with bone metastases
      from breast cancer is well established. We undertook an evaluation of palliative
      radiotherapy utilization rates in breast cancer patients who received
      bisphosphonates for the treatment of bone metastases in a major Canadian cancer
      center. METHODS: Charts and electronic files of breast cancer patients with bone
      metastases who had received either clodronate or pamidronate at any time between
      January 2000 and December 2001 at our center were retrospectively reviewed. The
      utilization rates of palliative radiotherapy in these patients were examined.
      RESULTS: The percentage of patients receiving bisphosphonates for the treatment
      of bone metastases who also received palliative radiotherapy to bone remained
      relatively constant over our study period in the range of 70%. In patients
      commenced on bisphosphonates before 1998, 42.9% received palliative radiotherapy
      as initial therapy for bone metastases, whereas in 2001 only 27.8% of patients
      received palliative radiotherapy before commencing bisphosphonate therapy. There
      has been a marked improvement in the time between the diagnosis of bone
      metastases and the commencement of bisphosphonates from a median of 446 days
      before 1998 to 21 days in 2001. At the same time, there was also an improvement
      in time between diagnosis of bone metastases and initiation of palliative
      radiotherapy from a median of 265 days before 1998 to 49 days in 2001.
      CONCLUSION: Use of bisphosphonates has not reduced the utilization rates of
      palliative radiotherapy in breast cancer patients with bone metastases. There is
      a trend of initiating bisphosphonates before delivery of palliative radiotherapy.
      The latter was also delivered earlier in the course of bone metastases.

PMID- 14577021
TI  - Cyclosporine absorption profiles in pediatric kidney and liver transplant
      patients.
AB  - Cyclosporine absorption profiling uses either the area under the concentration
      curve in the first 4 h post dose, AUC(0-4), or the concentration 2 h post dose
      (C2) to optimize immunosuppression in adult kidney and liver transplantation. We
      characterized C2 versus AUC(0-4) relationships over time after transplant and
      across transplant indications in 56 pediatric transplant patients. There were 36
      kidney transplant patients aged 9.7+/-3.9 years. Nineteen of these patients were
      studied in the de novo period on day 7 post transplant and 17 in the maintenance
      phase more than 1 year post transplant. In addition, 20 liver transplant patients
      aged 8.9+/-4.2 years were studied in the maintenance phase. All patients had five
      blood samples collected over the 12-h dose interval that were analyzed by
      validated assay methods at a central laboratory. Pediatric C2 values were 1,463+/
      658 ng/ml for de novo kidney, 954+/-322 ng/ml for maintenance kidney, and 619+/
      339 ng/ml for maintenance liver transplant patients. C2 was a strong predictor of
      AUC(0-4) in all three pediatric groups, with coefficients of determination (
      r(2)) ranging from 0.861 to 0.936. Although data were limited from the de novo
      period, the C2 versus AUC(0-4) regression was consistent over time after
      transplant and between transplant indications, with a regression slope of 2.50 in
      de novo kidney, 2.54 in maintenance kidney, and 2.76 in maintenance liver
      transplant recipients. These slopes were also comparable to that in adult
      maintenance kidney transplant patients (2.60). In conclusion, C2 versus AUC(0-4)
      relationships demonstrated consistency over time (de novo vs. maintenance phase),
      between transplant indications (kidney vs. liver), and across age groups
      (pediatric vs. adult patients). Average C2 values achieved with current pediatric
      cyclosporine dosing practices cluster around the target C2 ranges recommended for
      adults.

PMID- 14577022
TI  - The effects of corticosteroids on behavior in children with nephrotic syndrome.
AB  - The objective of this study was to measure the frequency and severity of the
      behavioral effects of high-dose oral steroid therapy in children with nephrotic
      syndrome. We conducted a prospective assessment of the behavior of 12 children
      using a standardized psychological questionnaire at the time of diagnosis and
      again after 4 weeks of steroid therapy. A group of control children was also
      assessed. There was a significant increase in the total behavior score ( P=0.03)
      and specifically in aggressive and poor attention behavior items in the group of
      nephrotic children compared with the control group. Four of the children with
      nephrotic syndrome developed abnormal behavior in the clinical range compared
      with none of the controls. In conclusion, children with nephrotic syndrome
      treated with high-dose oral steroids are at risk of developing clinically
      relevant behavioral changes.

PMID- 14577023
TI  - Laparoscopic cholecystectomy in cirrhotic patients.
AB  - BACKGROUND: This study aimed to evaluate the safety of laparoscopic
      cholecystectomy for patients with cirrhosis. METHODS: The records of 22
      laparoscopic cholecystectomies performed in patients with cirrhosis Child-Pugh A
      and B, from January 1995 to July 2001 were retrospectively reviewed. RESULTS: No
      deaths occurred. Conversion to open cholecystectomy was necessary in two cases.
      The average operative time was 115 min, which was significantly shorter than that
      for patients undergoing open cholecystectomy. None of the patients required blood
      transfusion. Intraoperative problems occurred in two patients who experienced
      liver bed bleeding. Postoperative morbidity occurred in 36% of the patients and
      included hemorrhage, wound complications, intraabdominal collections, and
      cardiopulmonary complications, but all were controlled. The patients were
      dismissed after an average of 4 days. CONCLUSION: The authors believe
      laparoscopic cholecystectomy can be performed safely in selected patients with
      cirrhosis Child-Pugh A and B who manifest indication for surgery. Laparoscopic
      cholecystectomy offers several advantages over open cholecystectomy: lower
      morbidity, shorter operative time, and reduced hospital stay.

PMID- 14577024
TI  - Laparoscopic transperitoneal adrenalectomy.
AB  - BACKGROUND: From November 1993 to May 2002 a total of 172 laparoscopic
      adrenalectomies were attempted in 152 patients in centers throughout the United
      Kingdom. RESULTS: The median age was 52 years (18-77 years). Sixty-three percent
      were female. Indications for resection were Conn's syndrome (60),
      pheochromocytoma (35), Cushing's disease (24), Cushing's adenoma (8), cortisol
      secreting carcinoma (1), other secreting tumor (2), nonfunctioning adenoma (17),
      congenital adrenal hyperplasia (4), metastatic disease (7), nonsecreting adrenal
      carcinoma (2), others (12). Median size of the lesions was 3.0 cm (0.5-20 cm).
      Median operating time was 65 min (30-170 min). Conversion to an open procedure
      was necessary in 10 patients (7%). Minor morbidity occurred in nine patients
      (5%). Major morbidity occurred in two patients (pancreatitis, peritonitis).
      Median hospital stay was 3 days (1-16 days). At median follow-up of 36 months (1
      105 months) five patients (4%) had persistent hypertension. No patient had
      evidence of recurrent hormonal excess. CONCLUSIONS: Laparoscopic removal of the
      adrenal gland should be considered the surgical procedure of choice in
      experienced minimally invasive centers.

PMID- 14577025
TI  - Preincisional local infiltration of levobupivacaine vs ropivacaine for pain
      control after laparoscopic cholecystectomy.
AB  - BACKGROUND: Postoperative pain is less intense after laparoscopic surgery than
      after open surgery. However, patients may gain additional benefit from a
      preincisional local infiltration of anesthetic. The aim of this study was to
      compare the analgesic efficacy of two local anesthetics, ropivacaine and
      levobupivacaine, for tissue infiltration as a means of improving postoperative
      pain control after laparoscopic cholecystectomy. METHODS: Using a randomized,
      double-blind study design, 57 American Society of Anesthesiologists (ASA) I and
      II patients scheduled for laparoscopic cholecystectomy were randomly assigned to
      receive local infiltration with 0.9% saline solution (Placebo group, n = 18),
      ropivacaine 1% (Rop group, n = 20), or levobupivacaine 0.5% (Lev group, n = 19).
      The local anesthetic was administered, prior to trocar placement, using the same
      technique and delivering the same volume (20 ml) for all three groups. The
      anesthetic technique was standardized for all groups. Postoperative pain was
      rated at 2 h, 4 h, and 24 h postoperatively by visual analogue scale (VAS) score.
      Cumulative analgesic consumption and adverse effects were also recorded. Data
      were analyzed by analysis of variance (ANOVA), followed by a post hoc test.
      RESULTS: The Lev and Rop groups did not differ significantly in their VAS scores
      at 2 h postoperatively, but the Lev group experienced significantly ( p < 0.001)
      less pain than the Placebo and Rop groups at 4 h and 24 h postoperatively. The
      Rop group registered significantly lower VAS scores ( p < 0.001) than the Placebo
      group at 4 h postoperatively. Additionally, the consumption of analgesics was
      significantly lower in the Lev group than in the Rop ( p < 0.01) and Placebo ( p
      < 0.001) groups, and patients in the Rop group consumed significantly less
      analgesics ( p < 0.001) than the to patients in the Placebo group. CONCLUSION:
      Local tissue infiltration with levobupivacaine is more effective than ropivacaine
      in reducing the postoperative pain associated with laparoscopic cholecystectomy.

PMID- 14577026
TI  - Successful treatment of radiofrequency-induced biliary lesions by interventional
      endoscopic retrograde cholangiography (ERC).
AB  - BACKGROUND: Radiofrequency ablation (RFA) of malignant liver lesions is
      considered a procedure with low morbidity. However, RFA performed close to hilar
      structures carries the risk of heat-induced biliary tract damage and subsequent
      septic episodes. METHODS: We performed an analysis of complications in 42
      patients with 211 liver lesions treated with a combined approach of liver
      resection and RFA. RESULTS: One patient died due to postoperative liver failure.
      There was one case of temporary liver dysfunction, one vena cava thrombosis, and
      six febrile episodes. Four of the six febrile episodes were related to bile duct
      injuries. They became evident 3-5 weeks after the procedure. All four patients
      were treated successfully by the placement of stents within the biliary tract.
      None of the patients developed a hepatic abscess. CONCLUSION: Biliary tract
      damage is a complication that can occur weeks after RFA. Immediate endoscopic
      intervention can obviate the occurrence of prolonged septic complications.

PMID- 14577027
TI  - Differences in perioperative coagulation between Japanese and other ethnic groups
      undergoing laparoscopic cholecystectomy.
AB  - BACKGROUND: Japanese patients experience fewer episodes of postoperative
      thrombosis than those in certain other countries. To investigate this phenomenon,
      we measured perioperative coagulation activation markers and conducted
      thromboelastography (TEG) in 27 Japanese patients undergoing laparoscopic
      cholecystectomy. METHODS: D-dimer, thrombin-antithrombin complex (TAT), and
      prothrombin fragment 1+2 (F1+2) were measured as coagulation activation markers.
      TEG was performed to measure reaction time (R), clot formation time (K), maximum
      amplitude (MA), and maximum elastance (ME). These measurements were performed
      before and after the operation and the day after the operation. RESULTS:
      Coagulation activation markers increased significantly postoperatively. With
      respect to TEG, MA and ME increased postoperatively. R and K did not change.
      CONCLUSION: Whereas clotting factor activation sthenia is common in Europe and
      North America, thrombocyte function sthenia occurs in Japanese patients. This
      difference may account for the differing incidences of phlebothrombosis in
      Japanese and white populations.

PMID- 14577028
TI  - Diagnosis and classification of inguinal hernias.
AB  - BACKGROUND: The aim of this prospective clinical study was to determine whether
      the presence of a hernia, its size, and its type can be established
      preoperatively by clinical and ultrasound, examination. METHODS: The study
      population comprised 220 consecutive patients referred to our department for the
      surgical management of an inguinal hernia. On admission, both inguinal regions
      were examined clinically and by ultrasound. All patients were operated on
      laparoscopically. RESULTS: In regard to the intraoperative findings for both
      inguinal regions, clinical and ultrasound examination for the diagnosis of
      inguinal hernia yielded a high total rate of accuracy of 93% respective 94%.
      However, when the same methods were used to differentiate between lateral and
      medial hernia, the total rate of accuracy fell to only 54% respective 62%. In the
      determination of inguinal hernia size, it was even lower: 50% respective 53%.
      CONCLUSIONS: Although a diagnosis of inguinal hernia can be established reliably
      by clinical and ultrasound examination, only an approximate classification is
      possible by these methods.

PMID- 14577029
TI  - Obesity does not adversely affect the outcome of laparoscopic antireflux surgery
      (LARS).
AB  - BACKGROUND: Because it has been suggested that obesity adversely affects the
      outcome of LARS, it is unclear how surgeons should counsel obese patients
      referred for antireflux surgery. METHODS: A prospective database of patients
      undergoing LARS from 1992 to 2001 was used to compare obese and nonobese
      patients. Patients were surveyed preoperatively and annually thereafter.
      Questionnaires were completed regarding global symptoms and overall satisfaction.
      RESULTS: Of the 505 patients, the body mass index (BMI) was <25 (normal) in 16%,
      25-29 (overweight) in 42%, and >30 (obese) in 42%. Although the operative time
      was longer in the obese group than in the normal weight group (137 +/- 55 min vs
      115 +/- 42 min, p = 0.003), the time to discharge and rate of complications did
      not differ. At a mean follow-up of 35 +/- 25 months, there were no differences in
      symptoms, overall improvement, or patient satisfaction. Further, the rates of
      anatomic failure were similar among the obese, overweight, and normal weight
      groups. CONCLUSIONS: Although the operative time is longer in the obese,
      complication and anatomic failure rates are similar to those in the nonobese at
      long-term follow-up. Obese patients have equivalent symptom relief and are
      equally satisfied postoperatively. Therefore, obesity should not be a
      contraindication to LARS.

PMID- 14577031
TI  - [Treatment of choroidal neovascularisations with photodynamic therapy].

PMID- 14577032
TI  - [The potential and the limits of photodynamic therapy - a review].
AB  - BACKGROUND: The spectrum of possible treatments for choroidal neovascularisation
      has been considerably increased with the introduction of photodynamic therapy. On
      the other hand the technical complexity and high cost associated with this new
      method require a pinpointed and dedicated application to achieve not only
      treatment benefits for the patients, but also not to exceed the available
      resources. This focussed application of the new treatment method can only be
      performed if the basics of diagnosis, indication, treatment and follow-up care
      are sufficiently known and used. MATERIAL, METHODS AND RESULTS: The standard
      treatment protocol, the results of published clinical trials as well as many
      published clinical observations are presented and discussed. CONCLUSIONS:
      Photodynamic therapy with verteporfin can prevent massive loss of vision in many
      cases of subfoveal choroidal neovascularisation, but the treatment outcome
      depends on many factors, the most important being the underlying disease process.
      Hence, indication for photodynamic therapy should adhere to the published
      treatment guidelines. In the future, additional medications or alterations of the
      treatment protocol might improve treatment outcome.

PMID- 14577030
TI  - Laparoscopic skills training.

PMID- 14577033
TI  - [On the effect of mutations of the fibroblast growth factor receptors as
      exemplified by three cases of craniosynostoses].
AB  - PURPOSE: Craniosynostoses are premature ossifications of cranial sutures. They
      occur isolated and syndromic. Syndromic craniosynostoses are mainly associated
      with mutations of the Fibroblast Growth Factor Receptors (FGFR) 1 - 3. This paper
      gives an overview of the etiology and pathophysiology of isolated and syndromic
      craniosynostoses and discusses the molecular genetic results in 21 index cases
      (19 seemingly isolated craniosynostoses, 2 cases with a clinical diagnosis of
      Crouzon's syndrome). METHOD: Mutation analysis in exons of the FGFR 1 - 3 known
      to be preferentially affected in craniosynostoses was performed on DNA samples
      from peripheral blood and bone specimen excised at the time of surgery to correct
      the craniosynostosis. RESULTS: In a girl with seemingly isolated plagiocephaly we
      identified a P250L (749C-->T) mutation in FGFR3. Her mother showed minor signs of
      craniosynostosis when the family was re-evaluated. She was shown to carry the
      same mutation. In two patients with suspected Crouzon's syndrome 2 different
      mutations were detected at the same nucleotide (1025G-->A or C) and confirmed the
      clinical diagnosis. No mutation was found in 18/19 seemingly isolated
      craniosynostosis cases. CONCLUSION: In contrast to syndromic forms isolated
      craniosynostoses are rarely associated with mutations in FGFR. The affection of
      further family members is a strong indication of involvement of FGFR mutations.
      Because of variable expressivity, parents should be examined carefully in
      isolated craniosynostoses to identify minor signs.

PMID- 14577034
TI  - [Current State of Corneal Pathology in Germany: Results of a Survey Conducted
      Among Members of the Cornea Section of the German Ophthalmological Society
      (DOG)].
AB  - BACKGROUND: The current situation of corneal pathology is widely unknown.
      Especially, there are no data available how corneal tissue is processed after
      penetrating keratoplasty. MATERIAL AND METHODS: In November 2002 a questionnaire
      with 15 questions was sent to all registered members of the cornea section of the
      German Ophthalmological Society (DOG) ( www.sektionkornea.org ) via email. Only
      one answer per eye clinic was allowed. RESULTS: Answers were obtained from 40 eye
      hospitals in which 3070 penetrating keratoplasties had been performed in 2001. 90
      % of the surgeons believe that ophthalmopathological investigations of excised
      corneal specimens are always or at least in some cases important, and 80 %
      examine 75 to 100 % of all corneal buttons. However, the corneoscleral rim is
      investigated only exceptionally. 45 % of all corneal buttons are examined by a
      pathologist within the hospital while 33 % of the corneal specimens are
      investigated by an ophthalmopathologist in an ophthalmopathological laboratory.
      In most cases the hospital itself has to bear the cost. Clinics with a high
      number of corneal transplantations do not differ from the average regarding the
      fate of corneal buttons. Morphological investigations and publications concerning
      the cornea are more frequent when an ophthalmopathological laboratory is
      available in the hospital. CONCLUSIONS: For most eye hospitals performing
      keratoplasties, the histopathological examination of excised corneal buttons is
      very important. It is carried out to a large extent by pathologists, but
      specialised ophthalmopathological laboratories are consulted when a profound
      expertise is needed. Thus, this survey is an argument for the preservation of
      these laboratories too. Based on the obtained data and on several comments by the
      section members initiatives to intensify histopathological investigations of
      excised corneal specimens should be undertaken.

PMID- 14577035
TI  - [Visual field in patients with arterial hypertension].
AB  - BACKGROUND: The aim of this study was to investigate the quantitative changes of
      visual field in patients with arterial hypertension using standard white-on-white
      perimetry. MATERIALS AND METHODS: Sixty-two patients (f : m = 33 : 29) with
      arterial hypertension without damage in end-organs were included and divided into
      three groups: Group 1: systolic/diastolic blood pressure: 120 - 139/80 - 89 mm Hg
      (n = 18, f : m = 14 : 4, mean age 55 +/- 13 years), group 2: systolic/diastolic
      blood pressure: 140 - 159/90 - 99 mm Hg (n = 24; f : m = 9 : 15, mean age 55 +/-
      12 years), group 3: systolic/diastolic blood pressure: 160 - 179/100 - 109 mm Hg
      (n = 20; f : m = 10 : 10, mean age 55 +/- 12 years). We compared these patients
      with an ophthalmological and healthy control group (systolic/diastolic blood
      pressure < 120/80 mm Hg, n = 20, f:m = 12 : 8, mean age 55 +/- 9 years). Beside
      the ophthalmological examinations (visual acuity, refraction, intraocular
      pressure, slit lamp and fundus examination) quantitative analysis of visual field
      by Octopus 1-2-3 perimeter was performed. Different parameters (mean deviation
      (MD), mean sensitivity (MS), loss variance (LV), pattern standard deviation (PSD)
      and the test-duration) were statistically compared using the Mann-Whitney-U test
      and the Wilcoxon test. RESULTS: Hypertensive retinopathy grade I - II was found
      in 10 patients with arterial hypertension. Statistic analysis showed no
      significant difference of MD, MS, LV, PSD and test duration between the patients
      with arterial hypertension and the control group (Mann-Whitney-U test: p > 0.05).
      There was also no significant difference between the three hypertonic groups
      (Mann-Whitney-U test: p > 0.05). CONCLUSIONS: The examination of visual field
      using standard achromatic automated perimetry based on investigation of the
      parvocellular system. Arterial hypertension, however, does not damage this
      parvocellular system enough to assess disturbances in the white-on-white
      perimetry. Further studies are necessary to clarify the value of Frequency
      Doubling Perimetry, which is based on the detection of early damage of the
      magnocellular system.

PMID- 14577036
TI  - [Evaluation of posterior capsule opacification after implantation of the Akreos
      Disc and Akreos Fit acrylic intraocular lenses - pilot studies].
AB  - In the course of the past few years the incidence of secondary cataract has
      reduced continually due to advanced surgical technique and better lens material
      and design. To evaluate the progression of posterior capsule opacification (PCO)
      and IOL-decentration after implantation of two hydrophilic acrylic intraocular
      lenses (IOL) we set up two pilot studies at two different ophthalmological
      surgical centres. After extracapsular cataract extraction 15 patients got the
      Akreos Disc-IOL (Bausch and Lomb) and 12 patients the Akreos Fit-IOL (Bausch and
      Lomb) implanted. Examinations were done over a period of 12 months. The protocol
      included the determination of visual acuity, an examination of the anterior
      segment, evaluation of IOL-decentration and the scoring of PCO with EPCO 2000 by
      digital photography of the posterior capsule. All patients showed a well centred
      IOL and stable visual acuity over 12 months. None had to undergo Nd:YAG
      capsulotomy. PCO was low and only slightly progressive over the time period.

PMID- 14577037
TI  - [Telemedicine in Ophthalmology: A Useful Tool in Store-and-Forward Counselling?].
AB  - Side by side with the progress in computers and imaging, telemedicine has already
      been used successfully in a large number of specialties of medicine. But high
      quality images are not always suitable for transfer via modem because of their
      file size. The present experimental study was conducted to determine the effects
      of image compression by the JPEG algorithm on image quality and on the
      reliability of diagnosis after compression. Digital photographs of the retina
      were taken and the JPEG compressed images assessed by an experienced
      ophthalmologist. The present study showed a high reliability of diagnosis and a
      good agreement between the observations taken at the patient and at the computer.
      For this reason, JPEG image compression algorithm is suitable for reducing image
      size for producing high-quality images manageable for transmitting via modem in a
      store-and-forward teleophthalmological system.

PMID- 14577038
TI  - [Hormone therapy for ophthalmoprophylaxis].
AB  - BACKGROUND: It has been demonstrated that HRT which was administered directly
      after the onset of the menopause had vascularprotective and neuroprotective
      effects. It has therefore hypothesised that eye function could benefit from such
      treatment. MATERIAL AND METHODS: Visual acuity, intraocular pressure, patient's
      gynaecological and ophthalmological history, especially HRT were obtained from
      women visiting the gynaecological and ophthalmological ambulance. Measuring the
      visus and the intraocular pressure of women with HRT from the gynaecological
      ambulance was easily undertaken in the neighbouring ophthalmological department.
      Unfortunately, due to absence of compliance a control group without HRT could not
      be recruited. Of 514 women, 402 without having had hysterectomy and adnexectomy
      could be included in the study from which data were received about the menopausal
      age. RESULTS: In the group of women with cataract HRT over 5 years was
      administered less often (two times) than in the group of women with glaucoma.
      Women mainly aged over 70 suffering from age-related conditions such as glaucoma
      and cataract almost never had HRT. Thus in the following only women aged up to 60
      have been of interest. 7 of 10 women being in the menopause for over 10 years
      with a visus higher than 0.7 received HRT. Only 1 of 10 women had a visual acuity
      less than 0.4. There was also a correlation between receiving HRT and intraocular
      pressure. In the group aged up to 60 without taking HRT 19 % had an intraocular
      pressure above 19. In women with HRT over 5 years this occurred in only 7 %.
      CONCLUSIONS: Initiating HRT in healthy women shortly after the onset of the
      menopause may have vascularprotective and neuroprotective effects for the eye.
      This is supported by the fact that HRT administered for more than 5 years to
      healthy women aged up to 60 years was associated with better visual acuity and
      normal intraocular pressure. This is further highlighted by ultrasound scan
      studies in the literature. Thus an ophthalmoprophylaxis could be expected, which
      has to be confirmed in prospective studies using suitable control groups.

PMID- 14577039
TI  - [Brivudine as an alternative systemic therapy to aciclovir and ganciclovir in
      acute retinal necrosis syndrome due to varicella-zoster virus].
AB  - BACKGROUND: Two cases of acute retinal necrosis (ARN-) syndrome caused by an
      infection with varicella zoster virus (VZV) are demonstrated. VZV-DNA was
      detected in vitreous biopsies by polymerase-chain-reaction (PCR). The course of
      retinal necrosis was decisively improved by changing antiviral therapy from
      aciclovir and/or ganciclovir to brivudine. MATERIAL AND METHODS: Patient 1: 51
      years, male, initial visual acuity 20/40; patient 2: 17 years, female, initial
      visual acuity 20/30. Both patients were immunocompetent and presented with an
      unilateral acute retinal necrosis syndrome with peripheral chorioretinitis,
      retinal vasculitis, vitreous inflammation and optic disc swelling, which resulted
      in progressive visual loss in a few days. RESULTS: In both patients VZV-DNA was
      detected in vitreous biopsies with PCR. A regression of intraocular inflammation
      and necrotic retinal foci was only observed after changing the initial systemic
      therapy from aciclovir (Zovirax) intravenously 1500 mg/day) and/or ganciclovir
      (Cymeven) intravenously 250 mg/day) to brivudine (Zostex) per os 500 mg/day).
      Vitreoretinal surgery was necessary in both patients because of rhegmatogenous
      retinal detachment. Visual acuity stabilised in patient 1 to 20/200 and in
      patient 2 to 20/25 during a follow-up of 16 or 32 months, respectively.
      CONCLUSION: Brivudine represents an alternative therapy, if standard treatment
      with aciclovir and/or ganciclovir failed in cases of ARN-syndrome due to presumed
      drug-resistant varicella zoster virus-subtypes. Complete remission and
      preservation of a satisfactory function can be achieved.

PMID- 14577041
TI  - [Dysplasia epiphysealis hemimelica of the carpus].
AB  - Dysplasia epiphysealis hemimelica is a rare benign osteochondromatous disorder
      which develops in childhood mostly on the epiphyses of the bones in the lower
      extremities. While the tarsal bones are often involved, it is very rare in the
      carpus. Four patients are reported. Two were treated operatively with good
      results. In consequence of the experience of Lamesch, an excision was not
      performed in the other two cases. The patients were followed up for many years
      with the findings of some reduction in size and figure. Therefore, it is
      recommended not to operate this special tumour as long as no functional
      disturbances will occur.

PMID- 14577042
TI  - [The posttraumatic carpal collapse--long-term results after midcarpal fusion].
AB  - PURPOSE: Midcarpal fusion is a reliable treatment for posttraumatic carpal
      collapse in the short or midlong term. The long-term results remain, however,
      unclear. The objective of this study was to assess the long-term clinical outcome
      but also the incidence of an arthrosis of the radiolunate joint or an ulnar
      translocation after excision of the scaphoid. METHOD AND MATERIAL: 37 patients
      after midcarpal fusion were reexamined after an average follow-up of 97 months
      clinically and radiologically. RESULTS: The average range of motion from
      extension to flexion was 62 degrees, the average grip strength changed from 69 %
      of the opposite side before surgery to 80 % after surgery. Pain in the verbal
      analogue scale improved from 2.7 preoperatively to 1.7 postoperatively. The
      Krimmer wrist score was 72, whereas 28 patients (76 %) reached a good or
      excellent result. The mean DASH score was 24 points. At the X-rays, ten patients
      (27 %) showed an arthrosis of the radiolunate joint and/or an ulnar
      translocation. Differences in clinical results between the groups with or without
      X-ray pathology were not statistically significant. From 107 patients with a
      midcarpal fusion in the time of interest, seven (6.5 %) had to be converted into
      wrist arthrodesis because of ongoing pain. CONCLUSION: Also in the long-term the
      motion-sparing midcarpal fusion offers a functional advantage over wrist
      arthrodesis.

PMID- 14577043
TI  - [Complications after midcarpal arthrodesis--attempt to analyse the pitfalls].
AB  - BACKGROUND: Midcarpal arthrodesis (MCA) with excision of the scaphoid is in our
      opinion a reliable procedure. Pitfalls and unsatisfactory results can be
      attributed to technical shortcomings during the operation or to poor indication.
      PATIENTS AND METHODS: From 1993 to 2001, 64 MCA were performed in 62 patients.
      Patients' subjective assessment of the results were evaluated according to the
      clinical records and telephone interviews concerning pain, function and patient
      satisfaction. Pre- and postoperative standard X-rays were analyzed. RESULTS:
      Among 27 patients operated because of SNAC wrist, the following severe
      complications were observed: three painful non-unions, which healed after
      revision doing the same procedure, one deep infection, treated by complete wrist
      arthrodesis later on. Among 25 patients operated because of SLAC wrist there was
      one non-union, treated by complete arthrodesis, two transient dystrophies, one
      marked malposition of the lunate and two patients with persistent pain without
      any recognisable reason on X-rays. Among seven patients operated because of SLAC
      wrist due to chondrocalcinosis, three had pain correlating to a too proximal
      position of the triquetrum, one of them together with a malposition of the lunate
      in the p.a. view. One other patient was dissatisfied without any obvious reason.
      Among three patients operated because of carpal instability persisting after
      closed reduction of perilunar dislocation, two had persistent pain also
      correlating to a proximal position of the triquetrum. One patient operated
      because of destruction of only the midcarpal joint complained of persistent pain
      on loading the wrist. The overall non-union rate was 6 %. After treating the
      complications 14 patients remained with unsatisfactory results, seven of them due
      to a special preoperative situation, four due to technical shortcomings during
      surgery. The other patients have been free of pain or much improved and able to
      work. Optimum results may only be obtained, if the lunate is carefully aligned.
      CONCLUSION: After SNAC and SLAC without more complex lesions of the carpal
      ligaments, good results may be predicted, a correct operative technique provided.
      Chondrocalcinosis is a relative contraindication to MCA.

PMID- 14577044
TI  - [Proximal row carpectomy in carpal collapse].
AB  - Proximal row carpectomy (PRC) is a generally accepted procedure in the treatment
      of an advanced radiocarpal arthrosis. The aim of this retrospective study was the
      evaluation of individual, functional and radiological results after proximal row
      carpectomy. Seventeen patients (15 male, two female) who had undergone proximal
      row carpectomy between 1991 and 1999, were reviewed. The most common indication
      was degenerative arthrosis secondary to carpal collapse associated with chronic
      scaphoid nonunion (SNAC), scapholunate advanced collapse (SLAC) deformity, late
      Kienbock's disease or perilunate dislocations. Clinical and subjective results
      were assessed using different scores (DASH-, modified Mayo wrist-score) and
      evaluating the individual wrist range of motion. Anteroposterior and lateral X
      rays were obtained for radiological analysis. At follow-up evaluation (mean 65.4
      months), the majority of patients reported pain relief and a significant
      increased range of motion for the operated wrist. Radiographical analysis showed
      degenerative changes at the radiocapitate articulation in ten patients. The
      intermediate-term results of this review would suggest that proximal row
      carpectomy is an effective procedure providing pain relief and a satisfactory
      range of motion in a variety of pathologic wrist disorders. Because of eventual
      radiocapitate arthrosis, we suggest PRC only in patients without significant
      degenerative changes at the proximal pole of the capitate or the lunate fossa.

PMID- 14577045
TI  - [The treatment of carpal collapse: proximal row carpectomy or limited midcarpal
      arthrodesis? A comparative study].
AB  - Between July 2000 and February 2002, 26 wrists were treated because of SLAC, SNAC
      and radiocarpal arthrosis after fracture of the distal radius. In 14 cases
      proximal row carpectomy (PRC) and in twelve cases limited midcarpal arthrodesis
      (LWF) was performed. Follow-up was after a mean time of 16.8 (PRC) and 13.7
      months (LWF) on ten wrists each. There was one complication in the PRC group and
      two in the LWF group. In all cases significant reduction of extension/flexion was
      observed with a mean range of motion of 69 degrees (PRC) and 71 degrees (LWF).
      The reduction of pain postoperatively was almost identical in both groups.
      Comparing grip-strength to the unoperated hand, we measured 26 compared to 39 kg
      in the PRC group and 28 compared to 46 kg in the LWF group, respectively. The
      DASH-score for the LWF group was 30 points and therefore better than the 36
      points for the PRC group.

PMID- 14577046
TI  - [Preliminary results with Cuenod's osteoligamentoplasty and capsulodesis for
      treatment of chronic scapholunate dissociation].
AB  - Until now, the ideal treatment of scapholunate dissociation has not yet been
      found. Cuenod described an operation with reconstruction of the dorsal part of
      the scapholunate ligament using a bone-ligament-bone autograft (dorsal
      trapezoidometacarpal II ligament) and an additional dorsal capsulodesis using the
      dorsal intercarpal ligament. From December 2000 until January 2002, we operated
      on twelve patients with symptomatic chronic scapholunate dissociation without
      signs of osteoarthrosis using Cuenod's procedure. Preoperatively as well as at
      follow-up patients were evaluated using a traditional wrist score and a DASH
      questionnaire in addition to clinical examination. X-rays of both wrists in two
      planes each and additional stress radiographs were done. All patients had an
      arthroscopy preoperatively and a CT scan before K-wire removal. The mean follow
      up time was twelve months. Clinical follow-up showed good results (traditional
      wrist score: 77 points; DASH-score: 27 points), but with regard to the good
      preoperative findings (traditional wrist score: 73 points; DASH-score: 28 points)
      no significant improvement. Postoperative X-rays showed a correction of static
      instability in three cases; in four cases we found a recurrent SL gap, which was
      interpreted as failure of the transplanted ligament. Until now, one patient had
      to be reoperated by STT-fusion. In our patients, Cuenod's operation showed
      different results. So, further studies are necessary to find the correct
      indications for applying this procedure.

PMID- 14577047
TI  - [Radioscapholunate fusion: long-term results].
AB  - INTRODUCTION: A review of the literature on long-term results (> or = 10 years)
      following radiocarpal arthrodesis as recommended by Gordon and King shows a
      paucity of data. Regarding the suitability of this procedure for treating
      radiocarpal arthrosis, especially in younger patients, we collected and evaluated
      long-term results of this surgical procedure. MATERIALS AND METHODS: Five
      patients (four men, one woman), who were treated between 1978 and 1984 at our
      institution with a partial radiocarpal arthrodesis as described by Gordon and
      King were reexamined clinically and radiologically by the same examiner in the
      year 1990 and again in the year 2000. RESULTS: All five patients were very
      satisfied with the result of the operation. Two patients were completely free of
      pain, whereas the other three patients reported minor pain in the radiocarpal
      joint when applying strain. The active range of motion in the operated joint
      remained constant over the years (mean 60 degrees dorsopalmar, 30 degrees
      ulnoradial, 162 degrees pro-/supination). Conventional radiological imaging
      showed proper osseous consolidation in the areas of partial arthrodesis, and
      slight degenerative intercarpal alterations in the distal radioulnar joint were
      observed. Complete postprocedural reintegration into the workforce, including
      manually demanding work, was achieved. CONCLUSIONS: The results of the follow-up
      examinations of these five patients indicate that satisfying long-term results
      can be achieved after radiocarpal arthrodesis provided that the procedure is
      correctly indicated and the operation is conducted in a technically proper
      manner. This method of radiocarpal arthrodesis is likely also appropriate for
      young manual labourers suffering from painful radiocarpal arthrosis after distal
      intraarticular fracture of the radius, scaphoid non-union, scapholunar
      dissociation and Kienbock's disease.

PMID- 14577048
TI  - [Scapho-trapezio-trapezoid arthrodesis (triscaphe arthrodesis)].
AB  - BACKGROUND: Scapho-trapezio-trapezoid (STT)/triscaphe fusion is used to stabilize
      the radial column of the wrist. However the reported results are controversial.
      MATERIAL AND METHODS: 111 patients were treated with STT fusion from 1992 to
      1997. Indications were chronic dissociation of the scapholunate joint (n = 15),
      idiopathic arthrosis of the scaphotrapeziotrapezoid joint (n = 11), Kienbock's
      disease in advanced stage (n = 84) and dislocation of the trapezium (n = 1). This
      study reviews the results after an average follow-up period of four years (range,
      two to eight years). RESULTS: Patients showed an average wrist motion (ROM) in
      extension and flexion of 81 % of the preoperative range and in radial and ulnar
      deviation of 68 % of the preoperative range. Preoperative pain values (VAS) were
      reduced 76 % (non-stress) and 55 % (stress). The average grip strength improved
      to 65 % of the contra-lateral side. Good results were reached according to the
      modified Mayo wrist score with a score of 66 points (71 points in arthritis of
      the STT joint; 62 points in Kienbock's disease, 60 points in SL-dissociation).
      The patients described low disability in the DASH scores, with an average of 27
      points. CONCLUSIONS: Our data show that STT fusion is reliable and effective for
      treatment and pain relief and offers reasonable functional results in the above
      mentioned indications.

PMID- 14577049
TI  - [STT-arthrodesis versus radial shortening osteotomy for Kienbock's disease].
AB  - Thirteen patients treated by STT fusion for Kienbock's disease (five stage 3 a,
      seven stage 3 b, and one stage 4) and 36 patients treated by radial shortening
      osteotomy (20 stage 3 a, 16 stage 3 b) were checked after 26 and 83 months
      average. The active range of motion and grip strength were compared by means of
      the Cooney score, discomfort and pain by the DASH score. X-rays were compared for
      the bone structure of the lunate and development or progress of carpal collapse.
      After STT fusion the active over-all range of motion decreased by about 10
      degrees, grip strength improved slightly by approximately 10 %, pain and
      discomfort improved well. Consolidation of the lunate was seen in ten of thirteen
      patients. The patients treated with radial shortening osteotomy could all improve
      their range of motion by about 10 degrees and the grip strength by about 20 %,
      whereas discomfort and pain persisted in some cases. X-rays showed consolidation
      of the lunate in cases of eleven patients stage 3 a and twelve patients stage 3
      b. Radiological results were not always corresponding to the clinical results and
      the patients' subjective estimation. A group of eight patients could be followed
      up after more than ten years; all of them showed excellent results. This may
      indicate the long-term result for those patients who benefit from radius
      shortening with early pain relief. We recommend both procedures for stage 3 a and
      3 b and suggest to decide from case to case, according to the needs of the
      patient. Ulna minus variance or the patient's wish to restore full active range
      of motion indicate radial shortening.

PMID- 14577050
TI  - [Computer-assisted planning and corrective osteotomy in distal radius malunion].
AB  - Corrective osteotomy of the malunited distal radius following fracture was
      performed in six patients using virtual planning and computer-assisted surgery.
      Radius joint angles and ulnar variance were assessed by CT scan and compared with
      the uninvolved wrist. Dorsal tilt was improved by 6 degrees, radial inclination
      by 3 degrees, radius rotation by 7 degrees and ulnar variance by 4.6 mm. Results
      were almost equivalent to the noninvolved radius. Corrective osteotomy in
      extraarticular malunited distal radius fracture was optimized by computer
      assisted planning and surgery.

PMID- 14577051
TI  - [Functional results two years after the treatment of a delayed diagnosed scapho
      capitate fracture syndrome].
AB  - The scapho-capitate syndrome (Fenton syndrome) is so rare that diagnosing is a
      real challenge to every clinician. Therefore, its primary treatment is not always
      possible. In this case we are reporting about a delayed open treatment of a
      Fenton syndrome ten days after the original injury. Open reduction was performed
      via a dorsal approach and the capitate fracture was stabilized with K-wires and
      the scaphoid fracture with screw fixation. After postoperative immobilization of
      the wrist using an external fixator for six weeks the patient was already able to
      work again only twelve weeks after surgery.

PMID- 14577052
TI  - Osteoblasts generate an osteogenic microenvironment when grown on surfaces with
      rough microtopographies.
AB  - Osteoblasts respond to microarchitectural features of their substrate. On smooth
      surfaces (tissue culture plastic, tissue culture glass, and titanium), the cells
      attach and proliferate but they exhibit relatively low expression of
      differentiation markers in monolayer cultures, even when confluent. When grown on
      microrough Ti surfaces with an average roughness (Ra) of 4-7 mum, proliferation
      is reduced but differentiation is enhanced and in some cases, is synergistic with
      the effects of surface microtopography. In addition, cells on microrough Ti
      substrates form hydroxyapatite in a manner that is more typical of bone than do
      cells cultured on smooth surfaces. Osteoblasts also respond to growth factors and
      cytokines in a surface-dependent manner. On rougher surfaces, the effects of
      regulatory factors like 1alpha,25(OH)2D3 or 17beta-estradiol are enhanced. The
      response to the surface is mediated by integrins, which signal to the cell
      through many of the same mechanisms used by growth factors and hormones. Studies
      using PEG-modified surfaces indicate that increased differentiation may be
      related to altered attachment to the surface. When osteoblasts are grown on
      surfaces with chemistries or microarchitectures that reduce cell attachment and
      proliferation, and enhance differentiation, the cells tend to increase production
      of factors like TGF-beta1 that promote osteogenesis while decreasing osteoclastic
      activity. Thus, on microrough Ti surface, osteoblasts create a microenvironment
      conducive to new bone formation.

PMID- 14577056
TI  - Genes of aging.
AB  - According to developmental genetics theories, aging is a genetically programmed
      and controlled continuum of development and maturation. Being dynamic and
      malleable processes, development and aging are controlled not only by genes but
      also by environmental and epigenetic influences that predominate in the second
      half of life. Genetic mutations affect many phenotypes in flies, worms, rodents,
      and humans which share several diseases or their equivalents, including cancer,
      neurodegeneration, and infectious disorders as well as their susceptibility to
      them. Life span and stress resistance are closely linked. Oxidative stress
      actually constitutes a defined hypothesis of aging in that macromolecule
      oxidative damage accumulates with age and tends to be associated with life
      expectancy. DNA methylation, a force in the regulation of gene expression, is
      also one of the biomarkers of genetic damage. The mitotic clock of aging is
      marked, if not guided, by telomeres, essential genetic elements stabilizing
      natural chromosomic ends. The dream of humans to live longer, healthy lives is
      being tested by attempts to modify longevity in animal models, frequently by
      dietary manipulation. The quest continues to understand the mechanisms of healthy
      aging, one of the most compelling areas of research in the 21st century.

PMID- 14577057
TI  - Interacting mediators of allostasis and allostatic load: towards an understanding
      of resilience in aging.
AB  - Individual differences in the aging process can be conceptualized as an
      accumulation of wear and tear of daily experiences and major life stressors that
      interact with the genetic constitution and predisposing early life experiences.
      The neuroendocrine system, autonomic nervous system, and immune system are
      mediators of adaptation to challenges of daily life, referred to as allostasis,
      meaning "maintaining stability through change." Physiological mediators such as
      adrenalin from the adrenal medulla, glucocorticoids from the adrenal cortex, and
      cytokines from cells of the immune system act upon receptors in various tissues
      and organs to produce effects that are adaptive in the short run but can be
      damaging if the mediators are not shut off when no longer needed. When release of
      the mediators is not efficiently terminated, their effects on target cells are
      prolonged, leading to other consequences that may include receptor
      desensitization and tissue damage. This process has been named "allostatic load,"
      and it refers to the price the tissue or organ pays for an overactive or
      inefficiently managed allostatic response. Therefore, allostatic load refers to
      the "cost" of adaptation. This article discusses the mediators of allostasis and
      their contributions to allostatic load as well as their role in resilience of the
      aging organism to stressful experiences.

PMID- 14577058
TI  - Effects of aging and stress on hippocampal structure and function.
AB  - Aging is often simply defined as the decline in various body systems and
      functions (eg, endocrine, cognitive, motor, etc) that occur with the passage of
      time, although the degree of deterioration can vary greatly across individuals.
      Increases in average life span have brought a greater focus on brain aging. There
      is an emphasis on understanding how aging contributes to a decline in brain
      functions (eg, cognition) because such a decline adversely affects the quality of
      life. The hippocampus is a key brain structure for cognition and the feedback
      control of the stress response. Herein we describe how the hippocampus changes
      with age and we examine the idea that age-related changes in the secretory
      patterns of the hypothalamic-pituitary adrenal (HPA) axis can contribute to
      hippocampal aging. We also examine the proposal that cumulative stress, perhaps
      due to compromised HPA axis function, can contribute to hippocampal aging by
      subjecting it to exposure to excessive levels of glucocorticoids. The aging
      hippocampus does not appear to suffer a generalized loss of cells or synapses,
      although atrophy of the structure may occur in humans. Thus, age-related
      cognitive impairments are likely related to other neurobiological alterations
      that could include changes in the signaling, information encoding, and plastic,
      electrophysiological, or neurochemical properties of neurons or glia. Dysfunction
      of the HPA axis sometimes occurs with aging, and while excessive glucocorticoids
      can disrupt cognition as well as hippocampal neuronal integrity, these are not an
      inevitable consequence of aging. The general preservation of cells and the
      plastic potential of the hippocampus provide a focus for the development of
      pharmacological, nutritional, or life-style strategies to combat age-related
      declines.

PMID- 14577059
TI  - Frailty in the elderly: contributions of sarcopenia and visceral protein
      depletion.
AB  - In any given population of free-living individuals 65 years of age and older, a
      substantial proportion (in the range of 6% to 25%) suffers from many of the
      elements of the syndrome of frailty. Although the syndrome is complex and still
      lacks a standard definition, there is a growing consensus about the signs and
      symptoms as well as the pattern of biological correlates that characterize this
      disorder. Patients who are afflicted with frailty typically exhibit loss of
      muscle strength, fatigue easily, are physically inactive, and have a slow-and
      often unsteady-gait, with an increased risk (and fear) of falling. They are
      likely to have a poor appetite and to have undergone a recent, unintentional loss
      of weight. Frail individuals are more likely than the nonfrail to experience
      impaired cognition and depression. They die sooner. Frailty, of course, is
      frequently complicated by a variety of coexistent illnesses. Among the biological
      correlates of frailty are sarcopenia (now readily measurable by dual-energy x-ray
      absorptiometry [DXA]), osteopenia (with an increased susceptibility to fracture),
      and activation of the inflammatory and coagulation systems, with a rise in
      inflammatory cytokines and several markers of coagulopathy. Age-dependent changes
      in a number of hormones also appear to promote the development of frailty in the
      elderly, particularly via their effects on muscle mass and strength, bone
      density, and by contributing to activation of the catabolic cytokines. In
      particular, serum levels of growth hormone (GH) and insulin-like growth factor-1
      (IGF-1) decline progressively during aging, and an association between reduction
      in the levels of these hormones and the involution of advancing age has been
      proposed. It is not yet known whether, in comparison with their nonfrail
      counterparts, frail individuals consistently manifest larger reductions in GH and
      IGF-1 (and other anabolic hormones). More research is needed before it will be
      known whether the benefits of administering GH to the frail elderly will outweigh
      the disadvantages. The poor appetite and weight loss that occur in many frail
      individuals are likely to be accompanied by a degree of visceral protein
      depletion (with its attendant morbidity), which can be estimated by making serial
      measurements of indicators of visceral protein status such as transthyretin
      (TTR), retinol-binding protein (RBP), and albumin. One characteristic of the
      frailty syndrome that distinguishes it from the effects of aging per se is the
      potential reversibility of many of its features. Progressive resistance training
      is feasible for many elderly individuals-even the oldest old-and, by increasing
      muscle mass and strength, can ameliorate or reverse important aspects of physical
      frailty. To the extent that visceral protein depletion has been caused by an
      inadequate intake of calories and protein, consumption of a more adequate diet
      can result in betterment of the frail patient's nutritional status, as determined
      by clinical improvement and favorable changes in TTR, RBP, and albumin.

PMID- 14577060
TI  - Drug therapy in the elderly.
AB  - This review examines altered drug responses during aging. The incidence of
      diseases and disorders that require drug treatment rapidly increases with
      advancing age; elderly patients tend to receive more medications more often and
      are therefore at a correspondingly higher risk of experiencing adverse drug
      reactions and interactions. The cognitive decline that commonly accompanies aging
      can exacerbate this problem, with elderly individuals becoming confused and
      forgetful about their prescribed medications. Physiological responses to drugs
      depend on several factors, including the time course of drug absorption,
      distribution, metabolism, and elimination in the body (pharmacokinetics), and the
      actions of these drugs at the intracellular level (pharmacodynamics). As people
      age, the pathophysiologic processes of aging will influence all of these factors,
      including the time course of drug concentration in the body and target organ
      sensitivity. These age-related pharmacokinetic and pharmacodynamic effects must
      always be kept in mind by those responsible for the medical care of the elderly.

PMID- 14577061
TI  - Impact of aging on the body's vascular system.
AB  - In this review, the effect of aging on the body's vascular system is considered
      in terms of potential mechanisms involved in target organ damage. First, the
      effects of aging on body fluid compartments, including changes that occur in
      subdivisions of the interstitial space (quite heterogeneous among organs), are
      described, with particular reference to the macromolecular composition of the
      fluid compartments. Second, the structure and function of different segments of
      the vascular system during aging are examined, with emphasis on: (1) large
      arterial conduits responsible for isolated systolic hypertension; (2) arteries
      most responsible for peripheral resistance (the "resistance arteries"); (3)
      microcirculation networks, including the vasa vasorum; and (4) large collecting
      veins that can have such an important effect on the cardiac output. Third, a
      detailed discussion is provided of the heterogeneous macromolecular composition
      of interstitial fluid compartments that are involved in the critical traffic of
      vital substrates, including pharmacologic agents, in transit from the systemic
      circulation to the various organs. The strategic position of interstitial fluid
      compartments, situated as they are between microcirculation networks and vital
      organs, is considered to be critically involved in the morbidity and mortality
      caused by the vascular diseases afflicting elderly persons. Finally, with respect
      to "physiological" and/or "morbid" aging, a re-examination is undertaken of the
      target organ damage observed in elderly individuals who suffer from isolated
      systolic hypertension, type II diabetes mellitus, peripheral vascular disease,
      chronic heart failure, and renal failure. Potentially new and noninvasive
      approaches available to clinicians for early detection of large artery rigidity
      are considered, along with the possible benefits of nonpharmacologic and/or
      pharmacologic interventions.

PMID- 14577062
TI  - Dysphagia and aspiration pneumonia in patients with Alzheimer's disease.
AB  - Dysphagia and aspiration pneumonia are the 2 most serious medical conditions seen
      in late-stage Alzheimer's disease (AD) patients. Pseudobulbar dysphagia is
      associated with weight loss, which is not always prevented by optimizing the
      management of the dysphagia. Failure of basic homeostatic mechanisms appears to
      play an important role in the nutritional status of these patients. Aspiration
      pneumonia is the most common cause of death in end-stage AD. The primary problems
      that predispose to aspiration pneumonia include a reduced level of consciousness,
      dysphagia, loss of the gag reflex, periodontal disease, and the mechanical
      effects of inserting various tubes into the respiratory and gastrointestinal
      tracts. The bacterial flora involved include the indigenous oral flora (among
      which aerobes predominate) and, in the hospital or nursing home setting,
      nosocomially acquired pathogens such as Staphylococcus aureus and various aerobic
      and facultative gram-negative bacilli that may colonize in patients. In addition
      to treatment with antibiotics, adequate symptomatic treatment of AD patients with
      pneumonia is a priority in order to relieve suffering.

PMID- 14577063
TI  - Small evidence for small incisions: pediatric laparoscopy and the need for more
      rigorous evaluation of novel surgical therapies.
AB  - BACKGROUND/PURPOSE: Laparoscopic surgery has been widely adopted for many
      pediatric surgical diseases for its potential to reduce morbidity and hospital
      stay. To date, no study has examined the qualitative state of evidence supporting
      the use of these techniques in children. The authors present a systematic and
      objective review of this evidence. METHODS: The authors identified all clinical
      reports during the last 10 years for the 3 most common pediatric surgical
      diseases managed laparoscopically (appendicitis, gastroesophageal reflux, and
      conditions requiring splenectomy). Standardized and previously validated quality
      assessment instruments were used to examine individual studies in 4 areas: (1)
      clinical relevance, (2) generalizability to clinical practice, (3) reporting
      methodology, and (4) strength of conclusions. RESULTS: The authors evaluated a
      total of 131 clinical reports (39 to 48 per disease). Ninety-three percent of all
      studies were retrospective, with single institution case reports accounting for
      the majority of evidence. Only 23% of studies used a control group of any kind.
      Randomized trials comprised 3% of all evidence (4 studies). Forty-five percent of
      nonrandomized studies were found to be of poor quality, and 55% were of fair
      quality by epidemiologic standards. The distribution of quality scores was not
      significantly different between the 3 operative indications examined (analysis of
      variance P =0.10). Randomized studies also were found to be of poor methodologic
      quality by standardized assessment criteria. CONCLUSIONS: The current body of
      evidence is of insufficient quality to justify the widespread adoption of
      laparoscopic techniques into accepted standards of care. Wider use of prospective
      studies such as multicenter databases and randomized trials are needed to clarify
      the indications and outcomes for these innovative techniques. Significant
      improvement in the quality of published observational studies is also warranted,
      and this may be facilitated by the adoption of standardized reporting guidelines
      specific to nonrandomized data.

PMID- 14577064
TI  - Further evidence on totally transanal one-stage pull-through procedure for
      Hirschsprung's disease.
AB  - BACKGROUND/PURPOSE: Fifteen consecutive children aged 20 days to 12 years with
      biopsy-proven Hirschsprung's Disease (HD) underwent a transanal pull-through
      procedure over a 17-month period. These patients have been divided into 2 groups.
      The first was a series of 9 patients, which helped us gain familiarity and
      confidence with technical and postoperative gestational problems, and the second
      series was of 6 patients, which fully corroborates and adds further evidence on
      the minimally invasive nature of the technique. Mucosectomy of aganglionic bowel,
      access to the peritoneal cavity, division of rectosigmoid mesenteric vessels,
      pull-through of normoganglionic colon, colectomy, and coloanal anastomosis all
      were performed transanally. Patients underwent a program of progressive anal
      dilatations and were assessed for postoperative clinical course, continence,
      constipation, diarrhea, postoperative enterocolitis, perianal excoriations, and
      anal stricture. RESULTS: Mucosectomy was done under direct vision. Operating time
      ranged from 150 to 350 minutes. The average length of bowel resected was 13.5 cm
      with a range of 8 cm to 25 cm. There were neither intraoperative nor significant
      postoperative complications. All but 2 patients accepted full oral feedings on
      postoperative day 2. Mean hospital stay in the first series of 9 patients was 7
      days, range, 5 to 12 days; that of the second series of 6 patients was 5 days,
      range, 4 to 8 days. All children currently experience 1 to 6 bowel movements per
      day at a follow-up period of 1 to 17 months. CONCLUSIONS: A one-stage pull
      through procedure for HD can be performed successfully with a completely
      transanal approach. This technique is associated with excellent early clinical
      results. Many more cases and a longer follow-up period will be required to
      compare long-term results with other one-stage procedures for definitive
      treatment of HD.

PMID- 14577065
TI  - Laparoscopic Swenson procedure--an optimal approach for both primary and
      secondary pull-through for Hirschsprung's disease.
AB  - BACKGROUND/PURPOSE: Several pull-through procedures are available for the
      surgical management of Hirschsprung's disease (HD) in children. The authors have
      adopted a laparoscopic approach since 1995, including laparoscopic Swenson
      procedure (LSw), both for one-stage primary and 2-stage secondary procedures. The
      aim of this study was to examine the role of LSw in children with HD in both
      primary and secondary procedures. METHODS: From January 1995 to December 2001, 42
      children with biopsy-proven HD underwent laparoscopic pull-through procedure for
      HD. This group included 29 children who underwent LSw, a detailed analysis of
      which forms the basis of this report. RESULTS: Sixteen children underwent a
      single-stage neonatal LSw; the median weight of this group at the time of surgery
      was 3.2 kg and the median age was 5 days. Secondary LSw was performed in the
      remaining 13 children, which included 3 children with total colonic HD who
      underwent laparoscopic total colectomy and LSw. The median operating time was 105
      minutes (range, 66 to 175 minutes). The median time to commence full diet was 48
      hours (range, 24 to 86 hours), and median time to return to normal play and
      activity was 72 hours (range, 48 hours to 5 days). There was no difference in
      operating time between primary and secondary pull-through procedures. There were
      no intraoperative complications, and no patient required open conversion.
      Postoperative ileus was noted in 3 children and enterocolitis in 2. The median
      hospital stay was 4 days (range, 2 to 6 days). Follow-up was between 6 months to
      7 years with a median follow-up of 2.2 years. At follow-up, 2 children required
      laparoscopic antegrade continence enema procedure. A satisfactory continence was
      noted in 15 of the 19 children who were older than 3 years at the time of last
      follow-up. CONCLUSIONS: LSw seems to be a suitable procedure for laparoscopic
      management of HD in children. LSw is safe and effective, both for primary and
      secondary type of pull-through procedures, with good short-term results.

PMID- 14577066
TI  - Fetal heart development in the nitrofen-induced CDH rat model: the role of
      mechanical and nonmechanical factors.
AB  - BACKGROUND/PURPOSE: In congenital diaphragmatic hernia (CDH), it was recently
      shown that early and late gestational lung underdevelopment is caused by
      nonmechanical and mechanical factors, respectively. Heart underdevelopment, which
      might predict lung hypoplasia, is commonly attributed to mechanical factors. The
      authors analyzed whether nonmechanical and mechanical factors affect cardiac
      growth and correlations between lung and heart weights during gestation. METHODS:
      Left-sided CDH was induced in pregnant Wistar rats by administration of nitrofen
      on E9.5. At selected gestational ages (E18, E20, and E22), the lungs and heart
      were harvested, weighed, and analyzed for DNA and protein contents. Left lung and
      heart weights were correlated at those gestational ages. Two experimental groups:
      nitrofen without CDH (nitrofen), and nitrofen with CDH (CDH), were compared with
      normal controls. RESULTS: At E18, both nitrofen-exposed groups presented similar
      and significant left lung (LL) hypoplasia. As gestation progressed (E20 and E22),
      in the nitrofen group left lung (LL) hypoplasia decreased, whereas in the CDH
      group LL hypoplasia was exacerbated relative to normal controls. In contrast, at
      E18 and E20, heart-to-body weight ratios as well as cardiac DNA and protein
      contents were reduced significantly in all animals exposed to nitrofen, with no
      significant differences observed between nitrofen and CDH groups. As gestation
      progressed, the difference between cardiac parameters in nitrofen-exposed and
      normal control rats diminished, and at E22 no significant differences were
      documented. In the CDH group, significant correlations were seen between lung and
      heart weights at E18 (r = 0.65; P <.05) and E20 (r = 0.4; P <.05), whereas at
      term gestation (E22) no significant correlation was observed (r = 0.21, not
      significant). CONCLUSIONS: Nonmechanical factors, which might be directed by
      nitrofen, play a role in the pathogenesis of lung and heart hypoplasia manifested
      precociously in fetal life, whereas mechanical compression might influence only
      lung growth during late gestation. Heart weight predicts lung weight only in
      early gestational ages.

PMID- 14577067
TI  - Patterns of management of congenital tracheal stenosis.
AB  - BACKGROUND/PURPOSE: Stenosing airway disease, including congenital and acquired
      lesions, is rare in the pediatric age group. Until recently, the outlook for
      patients with congenital tracheal stenosis (CTS) was dismal because medical
      management was the only way of treatment. Surgical and endoscopical techniques
      developed in the last years have improved the prognosis. This report reviews the
      short and long-term outcomes of a single-institution experience in the management
      of CTS in children, comparing different treatment modalities. METHODS: From 1991
      to 2002, 13 cases of CTS have been managed in the authors unit. Respiratory
      symptoms varied from mild stridor on exertion to severe distress. Bronchoscopy
      established the diagnosis in all cases. According to clinical and endoscopical
      features, patients have been classified into 3 groups. The following data have
      been studied in each case: sex, age at diagnosis and treatment, anatomic type,
      associated anomalies, treatment modality, complications, outcome, and time of
      follow-up. RESULTS: Seven girls and 6 boys have been included in this study. Age
      at diagnosis ranged from 3 days to 7 years (median, 8 months), and 77% showed
      associated anomalies. Four patients presented mild or no symptoms and have been
      treated expectantly. The other 9 patients have been operated on because of
      persistent or severe symptomatology. The following procedures have been
      performed: costal cartilage tracheoplasty (n = 5), tracheal resection (n = 3),
      slide tracheoplasty (n = 2), endoscopical dilatation (n = 3), and laser resection
      (n = 1). Three patients required 2 or more procedures, and there were 3 early
      deaths, all after costal cartilage tracheoplasty. Overall mortality rate in the
      series is 23%. Follow-up is complete in all survivors (n = 10) ranging from 6
      months to 10 years (mean, 4.7 years). CONCLUSIONS: Selection of the type of
      treatment depends on the patient's clinical status and the anatomic pattern of
      the stenosis. In symptomatic cases of short-segment stenoses the authors prefer
      tracheal resection with end-to-end anastomosis; for long-segment stenoses, slide
      tracheoplasty is the procedure of choice.

PMID- 14577068
TI  - Thoracoscopic treatment of spontaneous pneumothorax in children.
AB  - BACKGROUND/PURPOSE: This study describes the authors experience and results with
      thoracoscopic treatment of spontaneous pneumotrorax (SP) in 22 children. METHODS:
      A total of 32 thoracoscopic procedures were performed in 22 children. The
      patients ranged in age from 9 to 21 years at the time of their first
      thoracoscopy. SP was primary in 9 and secondary in 13 patients. Pleurodesis was
      performed in all thoracoscopies using talc in 28 and pleural abrasion in 4
      procedures. In 2 of these, apical pleurectomy was added to abrasion. Blebectomy
      was the additional surgical procedure associated with pleurodesis in 4 patients.
      RESULTS: Thoracoscopy usually was performed with the patient under general
      anesthesia. In children with severe respiratory insufficiency, regional
      anesthesia was used. The mean operative time was 42.6 minutes (range, 8 to 114
      minutes). The mean time of postoperative chest tube drainage was 4.6 days (range,
      2 to 12 days). Three patients with cystic fibrosis had prolonged air leak lasting
      longer than 7 days after thoracoscopy. None of them required an additional
      surgical intervention, and the air leak ceased in 8, 8, and 12 days with
      continuous suction. One patient required a repeat thoracoscopy for bleeding from
      an intercostal artery on postoperative day one. The mean follow-up was 4 years
      (range, 2.5 months to 14 years). There have been 2 partial recurrences (6.25%),
      both in patients with secondary SP, which were treated by a repeat thoracoscopy
      and talc pleurodesis. CONCLUSIONS: Thoracoscopic treatment of SP is safe and
      effective in children. It can be performed under regional anesthesia also in
      children with severe respiratory insufficiency. Because the complications and
      recurrences are encountered more frequently in children with an underlying lung
      disease, special care in surgical manipulation is required in this subgroup of
      patients with SP.

PMID- 14577069
TI  - Splenectomy attenuates intestinal ischemia-reperfusion-induced acute lung injury.
AB  - BACKGROUND/PURPOSE: Intestinal ischemia-reperfusion (IIR) induced acute lung
      injury (ALI) has been documented. Kupffer cell blockage with gadolinium chloride
      (GdCl(3)) has been shown to attenuate IIR-induced ALI. However, the effects of
      splenic monocytes/macrophages on IIR-induced ALI has not been studied previously.
      In the current study, the authors aimed to investigate the role of splenectomy in
      IIR-induced ALI. METHODS: Forty-eight rats were divided randomly into 6 groups as
      follows: SHAM, SHAM + KCB, SHAM + SPLN, IIR, IIR + KCB, IIR + SPLN. Two hours of
      ischemia and 1 hour of reperfusion has been applied by clipping the SMA. GdCl3
      was given 24 hours before experiment. Splenectomy was done just before SMA
      clipping. Lung levels of tumor necrosis-factor (TNF), interleukin (IL)-6,
      myeloperoxidase (MPO), and malondialdehyde (MDA) were assayed biochemically. Lung
      leukosequestration was determined by counting PMNLs histologically. Kruskal
      Wallis and Mann-Whitney U tests were done; P values less than.003 were considered
      significant. RESULTS: Polimorphonuclear leukocyte (PMNL) counts and biochemical
      parameters in the IIR group were significantly higher than the other groups (P
      <.003). When compared with IIR group, PMNL counts and biochemical parameters were
      significantly decreased in the IIR+KCB and IIR+SPLN groups, respectively (P
      <.003). However, they were still significantly higher than their sham-operated
      controls (P <.003). CONCLUSIONS: This study documents that splenectomy attenuates
      ALI as well as Kupffer cell blockage. Spleen, an important component of
      mononuclear phagocytic system as liver Kupffer cells, might play an important
      role in the IIR-induced ALI.

PMID- 14577071
TI  - The Kasai portoenterostomy for biliary atresia: A review of a 27-year experience
      with 81 patients.
AB  - PURPOSE: The aim of this study was to utilize clinical outcome methodology
      through multivariable analysis of perioperative factors to predict a successful
      Kasai-portoenterostomy (PE). METHODS: Records of 81 patients treated for biliary
      atresia (BA) were reviewed. Outcome was defined as successful if the patient was
      alive and had no liver transplant (LT). To predict future successful or failed
      PE, patients were categorized at 6 months post-PE into 2 groups: Success: direct
      bilirubin (DB) less than 2.0 mg/dL; Failure: DB greater than 2 mg/dL, or the
      patient was listed/had undergone LT, or had died. Groups were analyzed for
      positive or negative predictive values (PPV, NPV) at 2 and 5 years after PE. Cox
      regression was used to determine risk factors for PE. RESULTS: PE was successful
      in 38% and failed in 62%. PPV of future success was 96% at 2 years post-PE and
      95% at 5 years post-PE, NPV of failure was 76% and 74%, respectively. Bridging
      liver fibrosis at the time of PE and postoperative cholangitic episodes were
      interdependent risk factors for a failed PE (P <.05). Other covariates showed no
      significant relationship for PE outcome. CONCLUSION: Classifying of patients 6
      months postoperatively allowed us to determine a successful PE outcome. Bridging
      liver fibrosis at the time of the Kasai, and the increased number of
      postoperative cholangitic episodes were predictive of a poor PE outcome.

PMID- 14577070
TI  - The spectrum of surgical jaundice in infancy.
AB  - BACKGROUND: Conjugated jaundice arising during infancy may be caused by a number
      of different surgical conditions. The aim of this study was to compare clinical
      features, management, and outcome of all types of surgical jaundice presenting in
      the first year of life. METHODS: A retrospective review was conducted of all
      infants born in the United Kingdom with jaundice caused by a surgical cause
      referred to the authors' institution from January 1992 to December 1999. RESULTS:
      There were 171 infants who could be separated into 3 specific groups: biliary
      atresia (BA, n = 137), inspissated bile syndrome (IBS; n = 14), and choledochal
      malformation (CM; n = 12) together with a group containing various miscellaneous
      conditions (n = 8). Infants with BA had higher bilirubin (P <.01) and aspartate
      aminotransferase levels (P <.001) and came to surgery earlier (P <.01) than
      infants with either IBS or CM. Infants with IBS and CM were more likely to be
      premature and have other malformations, respectively. Ultrasound scan was the
      principal investigation in the differentiation of BA from other causes of
      jaundice. Accurate prelaparotomy diagnosis was made by percutaneous liver biopsy
      in 87% of cases later shown to be BA. Currently, 88 (64%) of children with BA are
      alive with their native liver postportoenterostomy, 4 have died, and 45 have
      undergone liver transplantation (with 1 death postoperatively). A policy of
      primary portoenterostomy for BA followed by transplantation, if necessary,
      resulted in a survival rate of over 95%. All children in the other diagnostic
      groups are alive and anicteric after appropriate surgical intervention.
      CONCLUSIONS: Approximately 80% of infants presenting with surgical jaundice have
      biliary atresia, whereas those with inspissated bile syndrome and choledochal
      malformations make up most of the remainder. Mortality in this age-group is
      confined to infants with BA, but even on these infants an overall survival rate
      of greater than 95% is currently expected.

PMID- 14577072
TI  - Clinical significance of 99mTc-DTPA-galactosyl human serum albumin liver
      scintigraphy in follow-up patients with biliary atresia.
AB  - PURPOSE: Technetium 99m DTPA-galactosyl human serum albumin (GSA) liver
      scintigraphy was performed in follow-up patients with biliary atresia, and its
      clinical significance was investigated. METHODS: Between 1994 and 2001, GSA liver
      scintigraphy was performed 153 times in 57 follow-up patients. HH15, LHL15, and
      H/L15 (HH15/LHL15) were obtained. Patients were divided into 3 groups according
      to the clinical status (good, n = 17; fair, n = 24; poor, n = 16). The
      correlation between these parameters and liver function tests was examined.
      Twenty-six patients of the 57 underwent 3 serial GSA scintigraphies and also were
      divided into 3 groups (good, n = 13; fair, n = 8; poor, n = 5). (3rd/1st)H/L15
      (3rd H/L15/1st H/L15) was obtained and compared. RESULTS: H/L15 had a correlation
      with serum albumin and serum cholinesterase. H/L15 was statistically different
      among 3 groups (good, 0.97 +/- 0.15; fair, 0.94 +/- 0.09; poor, 1.12 +/- 0.21; P
      <.05). Although most patients in the good (10 patients; 76.9%) and fair (7
      patients; 87.5%) groups showed (3rd/1st)H/L15 of less than 1.1, 3 patients (60%)
      in the poor group showed (3rd/1st)H/L15 of more than 1.1. (3rd/1st)H/L15 in the
      poor group was significantly higher than those in good and fair groups (P <.05).
      CONCLUSIONS: Technetium 99m-GSA liver scintigraphy is useful to assess the
      functional hepatic reserve in follow-up patients with biliary atresia. Serial
      assessment with GSA scintigraphy can provide the trend of the patient's liver
      condition and can estimate the prognosis of the liver.

PMID- 14577073
TI  - Recurrent inflammatory pseudotumors in children.
AB  - BACKGROUND/PURPOSE: pulmonary (PPT) and extrapulmonary pseudotumors (EPPT) are
      uncommon benign tumors, which, in general, do not recur after complete resection.
      Recurrence rates for both types of pseudotumors are undocumented in a large
      population of children, and the salient features of potential recurrences are
      unspecified. METHODS: This is a report of 15 children with PPT and EPPT; 3
      children had a recurrence. These pseudotumors recurred despite adequate primary
      resection of all gross disease at first presentation. The literature was reviewed
      to determine rate of recurrence for PPT and EPPT and also to document features
      common to recurrent pseudotumors. RESULTS: Overall recurrence rate for
      pseudotumors was 14%. PPT and EPPT, which were not confined to a single organ,
      had a high chance of recurrence (46% and 30%, respectively) compared with PPT and
      EPPT, which were confined to a single organ (1.5% and 8%, respectively).
      Recurrences have appeared between 3 months and 7 years. Intraabdominal EPPT
      accounts for more than 75% of the EPPT recurrences. CONCLUSIONS: PPT and EPPT
      recur more frequently than anticipated. All pseudotumors, which on initial
      presentation extend beyond the confines of a single organ, have a high chance of
      recurrence despite what appears to be adequate resection. Children with
      pseudotumors that extend beyond a single organ, require frequent postoperative
      evaluation for recurrence and may be candidates for chemotherapy or radiotherapy
      at the time of initial resection.

PMID- 14577074
TI  - Jessop and the Wilms' tumor.
AB  - The earliest specialists in the field of pediatric surgical oncology were the
      surgeons of 19th century Europe, particularly Billroth, Kocher, and Wilms.
      However, the first successful nephrectomy for a Wilms' tumor in a child was
      performed by a less famous name, Thomas Richard Jessop (1837-1903) at the Leeds
      General Infirmary on June 7, 1877. Jessop ultimately became Vice President of the
      Royal College of Surgeons of England and was a gifted teacher, being at the
      forefront in the development of medical education outside of London as first
      Professor of Surgery in Leeds. The clinical case history and operative procedure
      of this first successful nephrectomy for Wilms' tumor in a child is presented.

PMID- 14577075
TI  - Continuous versus intermittent administration of human endostatin in xenografted
      human neuroblastoma.
AB  - PURPOSE: The authors examined whether recombinant human endostatin
      (rhEndostatin), an antiangiogenic agent, is effective against a human
      neuroblastoma cell line (designated TNB9) using a human neuroblastoma xenograft
      model and investigated whether continuous infusion is more effective than
      intermittent administration. METHODS: In the first experiment, when tumors on the
      back of nude mice reached a weight of 90 to 95 mg, rhEndostatin, 10 mg/kg/d mouse
      weight, was administered subcutaneously to the mice (n = 5) every day for 10
      consecutive days. In the second experiment, the same daily dose of rhEndostatin
      was administered continuously to the TNB9-bearing mice (n = 6) via subcutaneous
      infusion pumps for 3 consecutive days with total dose being 30% of that in the
      first experiment. Nestin and factor VIII expression levels were studied
      immunohistochemically to elucidate whether histologic evidence of the effects of
      rhEndostatin was present on day 4 in the second experiment. RESULTS: In the first
      experiment, relative tumor weight in treated mice (n = 5) was significantly less
      than that in controls (n = 12) on day 2 only after treatment initiation (P <.05).
      The maximum inhibition rate (MIR) of TNB9 xenograft growth by rhEndostatin was
      46.4%, indicating lack of efficacy. In the second experiment, the effects of
      rhEndostatin were much more marked than those in the first experiment, with an
      MIR of 60.7%. The mean relative tumor weight in the treated group (n = 6) in the
      second experiment was significantly less than that in controls (n = 10) on days
      2, 4, and 6 (P <.01) as well as on days 8 and 10 (P <.05). Nestin staining in the
      endothelium of control tumors (n = 2) was marked, whereas it showed a loss of
      fibrillar structure in rhEndostatin-treated tumors (n = 2). The number of vessels
      immunostained with antifactor VIII antibody was markedly reduced in tumors (n =
      2) from rhEndostatin-treated mice compared with that in tumors from control
      animals (n = 2). CONCLUSIONS: Continuous administration of rhEndostatin resulted
      in more significant tumor regression than intermittent administration of the
      agent in the same model. This indicates that rhEndostatin, if administered in
      continuous fashion, could become an effective agent for treating patients with
      neuroblastoma in the future.

PMID- 14577076
TI  - Alterations of enteric nerve plexus in experimental gastroschisis: is there a
      delay in the maturation?
AB  - BACKGROUND/PURPOSE: After surgical correction of gastroschisis, intestinal
      transitory hypoperistalsis usually occurs. Long-term parenteral nutrition often
      is necessary leading to a higher morbidity associated with this malformation. The
      etiology of this transitory intestinal hypomotility is unknown. It may be caused
      by a reversible inflammatory process in the intestinal wall or other causes,
      including an alteration of the maturation of intestinal neural plexus, because
      the disturbance disappears spontaneously after a variable period. The aim of this
      work was to study the neuronal cells of the myenteric plexus of the fetal
      intestine in experimental gastroschisis. The main hypothesis was that the
      transitory intestinal dismotility seen in gastroschisis could be secondary to
      alteration in the maturation of the enteric nervous plexus. METHODS: Twenty-seven
      time-mated rabbits, on gestational day 25, were submitted to a midline
      laparotomy; the gravid bicornuate uterus was exposed and opened, and the more
      distal fetuses relative to the vaginal opening had the abdominal wall opened by a
      small incision to produce gastroschisis (n = 29). The fetuses not submitted to
      gastroschisis were used as controls (n = 12). The amniotic fluid was carefully
      aspirated from the opened uterus and saved for later repositions. On gestational
      day 30, the does were again submitted to general anesthesia, and the fetuses were
      delivered by cesarean section. The fetal intestine was removed, the adjacent
      mesentery excised, and intestinal specimens were harvested for histologic
      studies. The specimens were stained for acetyl-cholinesterase activity (AChE) to
      assess the maturity of the nervous enteric cells and for lactate dehydrogenase
      (LDH) that identify specifically immature nervous cells. The histologic sections
      stained by LDH were submitted to histomorphometric analysis of the nervous cells
      through an image system analysis (Kontron 300). The results were submitted to
      statistical analyses (P <.05). RESULTS: Macroscopic alterations of the fetal
      gastroschisis intestine are similar to the human findings: shortening of the
      intestine, intestinal wall thickening, and a hypertrophied muscular layer. In the
      gastroschisis group, histologic AChE activity was decreased in comparison with
      control intestines. The histomorphometric assessment in slices stained with LDH,
      which identify immature nervous cells, showed that the neuronal intestinal cells
      of the gastroschisis group were significantly smaller and more numerous relative
      to the control group. CONCLUSIONS: There were significant differences in the
      nervous plexus of the intestine of fetuses with gastroschisis relative to the
      controls. The observed morphologic changes may be caused by alteration in the
      maturation of the intestinal neuronal in gastroschisis. This alteration may
      explain the transitory intestinal hypomotility observed in infants after surgical
      correction of gastroschisis.

PMID- 14577077
TI  - Percutaneous endoscopic gastrostomy: the technique of choice?
AB  - BACKGROUND/PURPOSE: The percutaneous endoscopic gastrostomy (PEG) is contested on
      the ground that it could cause gastroesophageal reflux (GER). The authors studied
      the complications of PEG to ponder the validity of this contraindication.
      METHODS: The authors followed up with a group of 81 patients subjected to PEG to
      assess their complications, GER in particular. RESULTS: In half of the patients,
      PEG was performed under deep sedation in the intensive care unit and the other
      half under general anesthesia. The procedure lasted about 12 minutes in both
      subgroups. Early complications were not observed. Late complications relating to
      the care of the tube were similar to those reported for other techniques. GER
      appeared in 8%, but surgical treatment was unnecessary, whereas in patients that
      presented GER before surgery, it subsided in 38%. A colocutaneous fistula
      observed in one patient was a consequence of previous interventions. CONCLUSIONS:
      PEG is minimally invasive, general anesthesia may be avoided, the procedure is
      rapid, major complications are conspicuously absent, and the incidence of GER is
      smaller than that associated with alternative techniques. In addition, the cost
      is low. The authors consider PEG the technique of choice because it has important
      advantages compared with open or laparoscopic techniques.

PMID- 14577078
TI  - Early enteral feeding after closure of colostomy in pediatric patients.
AB  - BACKGROUND/PURPOSE: The aim of this study was to determine the benefits and
      adverse effects of protocolized early postoperative enteral feeding in pediatric
      patients undergoing a closure of colostomy. METHODS: Pediatric patients,
      completely treated for anorectal malformation, who underwent a closure of
      colostomy during September 2000 and May 2002 received early postoperative feeding
      according to the authors' protocol (EF group). Retrospective data of consecutive
      patients operated on from March 1998 to August 2000 who received traditional
      feeding practice were used as a control (TF group). The protocol began with a
      small volume of formula or breast feeding within the first postoperative day.
      Volume allowance was advanced every 4 hours up to the daily maintenance volume.
      Full feeding was defined as when the patient was able to tolerate at least 80% of
      daily maintenance volume. TF group received nothing by mouth until documentation
      of bowel function. The groups were compared with regard to postoperative stay,
      postoperative hour of full feeding, first bowel movement, and adverse effects.
      Statistical analyses were performed with chi2 test, Student's t test, and Mann
      Whitney U test. RESULTS: There were 34 and 30 patients in EF and TF groups,
      respectively. Median age of the patients was 13 months, and median weight was
      8.39 kg. Except for the associated anomalies, which were found more in the EF
      group, there were no differences in the demographic characteristics of the 2
      groups. On average, feeding was initiated at 19.7 (16 to 24) hours in the EF
      group and 51.7 (18 to 92) hours in the TF group (P <.01). Median full feeding
      hours were 45.5 and 70.5 hours in the EF and TF group, respectively (P <.01).
      First bowel movement in the EF group was recorded at the average of 4.14
      postoperative nurse shifts, compared with 5.96 shifts in the TF group (P <.01).
      Postoperative stay was significantly reduced from the average of 6.1 days to 4.5
      days (P <.01). The overall hospital expenses were not significantly different
      between the 2 groups. (203.95 dollars US in TF group and 198.50 dollars US in EF
      group; P =.75) There was 1 vomiting case in the EF group that was temporary and
      resolved spontaneously. Septic complications were noted in 8 patients in the EF
      group and 6 patients in the TF group (P =.27). The majority were uncomplicated
      urinary tract infections. CONCLUSIONS: Early feeding after a closure of colostomy
      in pediatric patients stimulated early bowel movement and reduced hospital stay
      with no increased adverse effects.

PMID- 14577080
TI  - Pediatric trauma caused by personal watercraft: a ten-year retrospective.
AB  - BACKGROUND/PURPOSE: Evidence indicates that young adults are at significant risk
      for powered personal watercraft (PWC)-related injuries. This article examines the
      nature of PWC injuries sustained in the pediatric population over a 10-year
      period. METHODS: Retrospective analysis was conducted of trauma registry charts
      on 66 pediatric patients, aged 5 to 19 years, hospitalized for PWC-related
      injuries between 1990 and 1999. The keywords PWC and Jet Ski were used to extract
      anonymous data from the National Pediatric Trauma Registry, which then were
      analyzed using descriptive statistics. RESULTS: The most common mechanism of
      injury was a collision with another PWC, a boat, or a fixed object (70%). A total
      of 55.1% of all the injury diagnoses involved the head, face, and/or neck, and
      72.7% of the injuries occurred to the operator of the PWC. A total of 83.3% of
      the patients required at least 1 surgical procedure, and 42.2% required admission
      to the intensive care unit. Four children (6.1%) died, and 28 (42.4%) of the
      children had disabilities as a consequence of the injury. CONCLUSIONS: Operation
      of PWCs can result in severe injures, death, and long-term disability in the
      pediatric population. Possible safety recommendations include minimum age
      regulations, operator training, operating regulations, design improvements, and
      required helmet use.

PMID- 14577079
TI  - Perforated appendicitis in children: is there a best treatment?
AB  - PURPOSE: This study was performed to provide outcome data for the development of
      evidenced-based management techniques for children with appendicitis in the
      authors' hospital. METHODS: This is a retrospective analysis of 1,196 consecutive
      children with appendicitis over a 5-year period (1996 to 2001) at a metropolitan
      hospital. RESULTS: The median age was 9 years (7 months to 18 years). The
      perforation rate was 38.9%, and the nonappendicitis rate was 5.6%. Predictors of
      perforation included age less than 8 years, Hispanic ethnicity, generalized
      abdominal tenderness, rebound tenderness, and increased number of bands. In
      perforated cases, the median length of stay was 5 days, and the complication rate
      was 13.5%. There was no difference in complication rates related to type or
      timing of antibiotics or related to the individual surgeon. There was no
      difference in infection rates related to type of wound management. CONCLUSIONS:
      Children with perforated appendicitis are treated effectively by a less expensive
      broad-spectrum antibiotic regimen, expeditious operation by open or laparoscopic
      technique, primary wound closure, and postoperative intravenous antibiotics until
      they are afebrile for 24 hours and have a white blood cell count of less than
      12,000/mm3. This approach is to be used in our prospective, randomized analysis
      of children treated on or off a clinical pathway.

PMID- 14577081
TI  - Temporary stretch of the testicular pedicle may damage the vas deferens and the
      testis.
AB  - BACKGROUND/PURPOSE: The authors aimed to investigate the effects of temporary
      stretching of the spermatic cord, a commonly performed manipulation during
      inguinal surgery, on the vas deferens and the testis. METHODS: Forty adult male
      Wistar-Albino rats were divided equally into 4 groups. The right spermatic cord
      and testis were exposed via a transverse suprascrotal incision. In the study
      groups, a continuous horizontal stretch force was applied to the vas deferens and
      vessels in a distal direction for 60 seconds. In group 1 (G1) a 1.25-Newton (N),
      and in group 2 (G2) a 0.75-N stretch force was applied. Group 3 (G3) and group 4
      (G4) served as sham and control groups, respectively. The animals were killed 28
      days later. Sections of the vas deferens were examined histologically and their
      dimensions measured. Both testes were excised, weighed, and examined
      microscopically. Kruskal-Wallis test and Mann-Whitney U test were used to compare
      means in the different groups. RESULTS: The mean wall thickness of the vas
      deferens was 378 +/- 133 mum in G1 and was significantly diminished compared to
      G2, G3, and G4, in which the mean wall thickness was 497 +/- 142 mum, 500 +/- 10
      mum and 521 +/- 95 mum, respectively (P <.05). The mean right testicular weights
      were 1.18 +/- 0.10 g and 1.23 +/- 0.17 g in G1 and G2, respectively, and each was
      significantly lower than in G3 (1.23 +/- 0.09 g) and G4 (1.25 +/- 0.08 g; P
      <.05). The mean right testicular weights showed no difference between G1 and G2
      (P >.05). Necrosis was seen in the right testes in 50.0% and 42.9% of the animals
      in G1 and G2, respectively. No histopathologic alterations were observed in the
      vas deferens in all groups. Microscopic examination of the left testes was
      normal. CONCLUSIONS: In an experimental animal model, temporary stretching of the
      spermatic cord resulted in significant thinning of the smooth muscle layer of the
      vas deferens and testicular atrophy.

PMID- 14577082
TI  - Laparoscopy for nonpalpable testes.
AB  - PURPOSE: Laparoscopy is now considered integral to the management of nonpalpable
      testes, although its benefits are not clearly documented. The authors
      prospectively determined the value of laparoscopy in patients with nonpalpable
      testes. METHODS: Between December 1997 and October 2001, 37 patients with 40
      nonpalpable testes were scheduled for laparoscopy followed by definitive
      treatment. Laparoscopy was cancelled in 4 patients (5 testes) because their
      testes became palpable under anesthesia. In the remaining 33 patients (35
      testes), it was determined at the time of surgery whether, as a consequence of
      laparoscopy: (1) retroperitoneal exploration was avoided (2) definitive treatment
      was facilitated. RESULTS: Laparoscopy did not alter the management of 27 testes
      (77%) that were treated through an inguinal incision with orchiopexy for 17
      testes (6 intraabdominal and 9 at the deep ring) and removal of 10 atrophic
      nubbins. It was only useful in avoiding retroperitoneal dissection for 5 (14%)
      vanishing testes, and it may have been of benefit for 3 testes treated with a 2
      stage Fowler-Stephens orchiopexy. CONCLUSIONS: The majority of our patients with
      nonpalpable testes could have been treated through an inguinal incision with
      laparoscopy being reserved for situations in which the testis was not identified
      on inguinal exploration.

PMID- 14577083
TI  - Massive ischemic intestinal necrosis at the onset of diabetes mellitus with
      ketoacidosis in a three-year-old girl.
AB  - A previously healthy 3-year-old girl had severe diabetic ketoacidosis complicated
      by hypovolemic shock. When her abdominal pain and acidosis failed to improve
      despite vigorous fluid resuscitation and insulin therapy, further investigation
      found an intestinal perforation. At laparotomy, gangrenous bowel was found,
      requiring an extensive enterectomy from the distal jejunum to the transverse
      colon; less than 90 cm of viable small intestine remained. The child survived a
      complicated postoperative course and currently is thriving on a normal diet.

PMID- 14577084
TI  - Extraabdominal desmoid tumor in a surgical scar of a patient with Sprengel's
      deformity.
AB  - Patients with an extraabdominal desmoid tumor have multiple minor bone
      abnormalities. The authors describe a rare case of an extraabdominal desmoid
      tumor that developed in a scar 2 years after surgery for Sprengel's deformity of
      the right shoulder in an 8-year-old girl. The association between the tumor and
      Sprengel's deformity has never been reported previously. Antecedent surgical
      trauma might play a role in the development of this tumor.

PMID- 14577085
TI  - Chromosomal translocation in mesenchymal hamartoma of liver: what is its
      significance?
AB  - Mesenchymal hamartoma of the liver is generally considered to be benign in
      nature, and surgical excision has been the treatment of choice. There have been 3
      reports on the association of cytogenetic abnormalities with this tumor, and the
      possibility of malignant potential has been raised. The authors report a fourth
      case with a previously unreported complex chromosomal translocation between
      chromosomes 11, 17, and 19 at bands q12, p11, and q13.3, respectively in all
      cells examined and discuss the significance of this finding.

PMID- 14577086
TI  - Paratesticular rhabdomyoma.
AB  - A case of rhabdomyoma of the spermatic cord in an infant with cryptorchidism is
      reported. This extremely rare tumor has not been described in an extrascrotal
      position or at such a young age. Differential diagnosis includes malignant
      rhabdomyosarcoma. Although fetal-type rhabdomyoma of the head and neck generally
      is a benign tumor, the prognosis of paratesticular fetal-type rhabdomyoma is
      unknown. Long-term follow-up is recommended.

PMID- 14577087
TI  - Small bowel complication caused by magnetic foreign body ingestion of children:
      two case reports.
AB  - Accidental ingestion of foreign bodies is a common pediatric problem. The
      majority of such cases occur between 6 months and 3 years. When several magnets
      are ingested, they can be attracted to each other through the intestinal wall,
      causing necrosis and intestinal perforation or fistula, so they should be removed
      while they are still in the stomach. The authors experienced 2 cases of unusual
      small bowel complication caused by the ingestion of magnets. The first case was
      in a 10-month-old boy with ileal perforation caused by to 2 ingested magnetic
      beads, and the second case was in a 22-month-old boy with ileo-ileal fistula
      caused by to 7 ingested magnetic beads.

PMID- 14577088
TI  - A case confirming the progressive stages of pyomyositis.
AB  - A teenage boy presented in the early stage of pyomyositis. He had neck pain,
      tenderness, and fever. A computed tomography scan showed inflammation in the
      sternocleidomastoid muscle with no fluid collection. This progressed to a pus
      filled drainable mass caused by Stapylococcus aureus. The authors describe this
      case to highlight the predictable stages and increase the index of suspicion to
      enhance its early recognition.

PMID- 14577089
TI  - Retained foreign body in a 14-year-old boy.
AB  - The authors describe a 14-year-old boy who presented at the emergency department
      after he deliberately inserted a soda can in his rectum 48 hours before
      presentation. The authors were able to remove the foreign body in the operating
      room by squeezing and twisting the upper round of the empty soda can, in this way
      changing the original cylinder shape into a conus-shape. Retained foreign bodies
      in the rectum of children are rare. The authors report our case and discuss the
      relevant literature.

PMID- 14577090
TI  - External jugular venous aneurysm: an unusual cause of a neck mass in a young
      child.

PMID- 14577092
TI  - Metastatic osteosarcoma causing intussusception.
AB  - Osteosarcoma is the most common malignant bone neoplasm. It has a very high
      metastatic potential, and lungs are the most common site of metastasis followed
      by bones. Multiagent chemotherapy has been reported to alter the biological
      behavior of the disease so that the tumor metastasizes to more rare sites such as
      brain, bowel, and soft tissues. The authors report a case of jejuno-jejunal
      intussusception caused by metastases from osteosarcoma.

PMID- 14577093
TI  - Gastric augmentation in isolated congenital microgastria.
AB  - A 10-month-old boy with isolated congenital microgastria is reported. This is an
      extremely rare condition with only 2 previous similar case reports. The patient
      was treated successfully with early gastric augmentation. Although the
      embryologic origin of this anomaly was widely believed to be in the fourth week
      of gestation, the anatomic features in the current case point to the arrest of
      development at least after the eighth week of fetal life.

PMID- 14577094
TI  - Laparoscopic distal pancreatectomy for traumatic pancreatic transection.
AB  - Laparoscopic pancreatic surgery has been discussed but remains relatively limited
      to resection for benign disease. Laparoscopic intervention for pancreatic trauma
      has been documented briefly, and the authors now report a case of traumatic
      pancreatic transection managed by laparoscopic distal pancreatectomy.

PMID- 14577095
TI  - Extrahepatic portal hypertension treated by anastomosing inferior mesenteric vein
      to left portal vein at Rex recessus.
AB  - For the treatment of recurrent bleeding despite sclerotherapy or clinically
      significant hypersplenism, portosystemic shunt procedures should be performed in
      cases of extrahepatic portal hypertension caused by extrahepatic portal vein
      thrombosis. A novel alternative to portosystemic shunt procedures in extrahepatic
      portal hypertension is mesenterico-left portal bypass. Portal vein thrombosis is
      bypassed by an autologous vein graft (usually left internal jugular vein)
      interposed between superior mesenteric vein and left portal vein. In the presence
      of an enlarged right gastroepiploic vein, the distal end of this vein can be
      anastomosed to left portal vein without disturbing its proximal end. Herein, the
      authors report a case of extrahepatic portal hypertension treated by anastomosing
      enlarged inferior mesenteric vein to left portal vein to bypass portal vein
      thrombosis.

PMID- 14577096
TI  - A rare case of combined type I and II first branchial sinus.
AB  - The authors report a rare case of first branchial sinus with combined Work's type
      I and type II characteristics. Instead of a sinus opening in the neck, this sinus
      opened above the angle of the jaw in the face. The facial nerve was significantly
      more superficial to the tympanomastoid suture line than normal. Early diagnosis,
      ensuring complete resection, and avoidance of facial nerve injury are challenging
      issues discussed here.

PMID- 14577097
TI  - Management of giant omphalocele in a premature low-birth-weight neonate utilizing
      a bedside sequential clamping technique without prosthesis.
AB  - Management of giant omphalocele in a full-term neonate is a challenging clinical
      situation. Even more challenging is giant omphalocele in a premature low-birth
      weight infant. The authors describe a successful staged noninvasive technique for
      the management of giant omphalocele in a premature, low-birth-weight neonate
      without the use of prosthetic material until delayed primary closure could be
      attempted.

PMID- 14577098
TI  - Congenital multifocal inflammatory pseudotumor: a case report.
AB  - Inflammatory pseudotumor is an uncommon benign tumor found in various sites
      throughout the body. The etiology is unclear with evidence to support both
      neoplastic and infective processes. The authors present a case with several
      unique features. It represents the first reported case detected antenatally. The
      tumor was found separately within the abdomen and thorax. The thoracic component
      of the tumor was managed without resection or ablative treatment but showed
      spontaneous regression.

PMID- 14577099
TI  - Use of a silastic silo for closure of the abdominal wall in a pediatric patient
      receiving a cadaveric split liver.
AB  - Presented is the successful management of a difficult abdominal wall closure
      after pediatric liver transplantation. A 5-week-old boy with biliary atresia
      underwent urgent cadaveric split liver transplantation. The left lateral segment
      of an adult donor was utilized. Postoperatively, abdominal skin and fascia could
      not be closed. A SILASTIC (Dow Corning, Midland, MI) silo was applied, and
      complete closure was possible 6 days later.

PMID- 14577100
TI  - A fighting chance.

PMID- 14577101
TI  - Vacant expression.

PMID- 14577102
TI  - Data briefing. Choice of A & E.

PMID- 14577103
TI  - Clinical management where medicine meets management. Network solutions.
AB  - Sexual health appears to be an ideal candidate for a managed clinical network,
      although there are doubts about whether networks deliver better patient care.
      With no dedicated staff, clinicians have to put in much of their own time to
      establish and run a network. For SWAGNET in south-west London, Inclusion is a
      problem. HIV teams are large and multidisciplinary--everyone needs to be
      represented.

PMID- 14577104
TI  - Mental health. Stop the rot.

PMID- 14577105
TI  - Law. Balance of payments.

PMID- 14577106
TI  - HSJ people. I spy.

PMID- 14577107
TI  - [The San Giacomo Hospital in Augusta through history, service, and culture].

PMID- 14577108
TI  - [Penetrating injuries of the neck: review of 16 operated cases].
AB  - BACKGROUND: Cervical lesions from penetrating trauma in the neck are increasing
      together with other types of trauma especially in big towns. Nevertheless in
      Italy a Register of Trauma is still lacking and no guidelines are available.
      Conservative management is also advocated and is still under discussion.
      Comparison of diagnostic tools and evaluation of different treatments in case of
      vascular damage is also expected. PATIENTS AND METHODS: A series of 16
      penetrating lesions of the neck including various degrees of severity were
      treated over a span of 5 year. The penetrating trauma was due to stab wound or
      similar causes in 11 cases; to gunshot wound in 3 and to traffic accidents in 2
      cases. All of them received surgical treatment. In 56% of cases (9/16) of cases
      vascular structures were involved, in 4 cases the aerodigestive tract was
      involved (25%), and in 1 the spinal cord was injured (6%) resulting in a Brown
      Sequard syndrome. Other patients presented with superficial lesions, and
      reconstruction of muscles by simple suture or ligature of veins could obtain
      complete healing. RESULTS: The penetrating trauma brought about death in 2 cases
      (1 stab wound, 1 gunshot wound), while 1 lesion of carotid artery and 4 lesions
      of jugular vein were successfully repaired. In 1 case of lesion in zone 3 a
      serious bleeding from damage to lingual artery was cured in spite of the minimal
      width of the external injury. Hypopharyngeal lesions could be treated in 2 cases.
      One was associated with lethal vascular damage. In 1 case of tracheal lesion with
      cervical hematoma and dyspnea, patency of the airways became the main concern and
      and a cannula was placed in the trachea. The Brown-Sequard syndrome could improve
      with rehabilitation therapy in 3 years. All of the minimal cervical lesions
      healed with uneventful course. CONCLUSIONS: The penetrating trauma in the neck
      may show various degrees of severity: nevertheless, no cervical penetrating
      trauma should be underestimated in spite of the minimal width of the lesion.
      Surgical exploration was invariably the preferred treatment in our experience.

PMID- 14577110
TI  - [Multinodular goiter as an organ disease: study of continual nodulogenesis.
      Biological bases indicating total thyroidectomy].
AB  - Multinodular goitre is a very common pathology among people especially female
      adult and represents more than 90% of the thyroid surgery. We analyzed 37
      patients, demonstrating that the whole gland is progressively affected by an
      incessant nodulogenesis and we confirm the necessity of total thyroidectomy in
      order to eliminate any persistent pathology.

PMID- 14577109
TI  - [A rare salivary gland neoplasm: cystadenolymphoma].
AB  - The authors, after having examined three recent cases, explain some basic
      concepts about diagnostics and therapy in cystadenolymphoma of salivary glands.
      As a matter of fact this neoplasia, in spite of its low frequency, is very
      important because of its still controversial etiopathology and recent tendency in
      increasing its incidence in females. Today the diagnostic protocol, undertaken
      after clinical examination, which is necessary, consists of ultrasonography or
      computerized tomography. But only postoperative histological examination gives a
      sure diagnosis and can point out main histomorphological characteristics of
      tumour. Therapeutic approach can be limited to conservative treatment, which is
      able to respect the parotid gland, its vascularization and innervation.

PMID- 14577111
TI  - [The treatment of inguinal hernia: experience of a Operative Surgery Unit].
AB  - INTRODUCTION: 550 patients submitted to surgical hernia reparation are reviewed
      for a retrospective analysis. PERSONAL EXPERIENCE: The case report shows a
      predominance of prosthesis reconstruction according to Trabucco (254 patients)
      and of the surgical technique of Shouldice (191 patients). Other procedures of
      the experience refer to the surgical techniques of Bassini (46 patients),
      Lichtenstein (46 patients), Mugnai/Ferrari (7 patients), Postenski (3 patients),
      Rives (2 patients), and Stoppa (1 patient). RESULTS: The reconstruction procedure
      was performed from a number of surgeons, all let free to choice the kind of
      operation following his personal skill and preference, but always in the most
      correct technique way. The results were satisfying in terms of short hospital
      stay, both precocious and late low complications, and always without failure.
      DISCUSSION: A first consideration is that there is no data from the literature
      that any prosthesis procedure offers a lower postoperative complication incidence
      than the Shouldice's technique, and our experience confirms this option.
      CONCLUSIONS: A surgeon can nowadays freely cultivate his preference for any of
      the possible procedures in reconstructing an inguinal hernia, but it is highly
      advisable that all the possibilities, also the pure surgical ones, remain in the
      surgeon's possibility of choice not to waste a precious previous surgical
      culture.

PMID- 14577112
TI  - [Spigelio's hernia. Anatomo-clinical considerations and description of 5 clinical
      cases].
AB  - Spigelian hernia, or ventro-lateral hernia is a rare clinical condition, it
      represents about 1.5% of hernial formation cases of the abdominal wall. It is
      localised laterally to the rectus muscle and emerges from the semilunar arch. The
      line, which joins the IX rib to the pubic tubercle, defines the limit between
      muscular and aponeurotic portion of trasversus abdominis muscle. Diagnosis often
      results misunderstood. As a matter of fact, this hernia has typically an
      intraparietal localization and the clinical picture seldom presents
      characteristic signs. The hernial sac and its content can be appreciated
      subcutaneously in only 2% of cases. It is estimated that about 50% of patients
      affected by this condition have a certain diagnosis before surgery. The early
      clinical signs are generally aspecific and deceitful, represented by oppressive
      grief and rarely by an abdominal wall tumor; it occurs that it starts with a
      complication: intestinal occlusion (23%), subocclusion (8%), strangulation (20%,
      but some authors report percentage up to 50%). We report 5 cases who came to our
      observation during the last 7 years; all patients underwent elective surgery, and
      specifically 3 patients in day surgery. Starting from the discussion of these
      cases, we review anatomy, etiology, clinical nature, instrumental investigation
      and surgical technique of this rare kind of hernia, comparing our experience to
      literature reported case histories.

PMID- 14577113
TI  - [Surgical treatment of carcinoma of the left colon and rectum as an emergency. A
      new method for assessing operative risk].
AB  - BACKGROUND/AIMS: The surgical treatment of the left colon and rectal cancer
      emergencies is still controversial. In our opinion the choices to be based on the
      general health status of the patient. METHODOLOGY: The authors analysed a series
      of 63 patients submitted to immediate resection and anastomosis. RESULTS: Factors
      significantly related to short term results were chronic heart disease, low
      albumin serum levels, and colonic perforation. The presence of a diverting
      colostomy did not provide a protective factor against anastomotic dehiscence. We
      constructed a Colorectal Tumours Emergencies Score made of the identified four
      factors in which the score of each factor is the approximated odds ratio (chronic
      renal failure 7 points, low albumin serum levels 6 points, heart disease 5
      points, colon perforation 4 points). Each patient was classified as Low Risk
      (CTES < 4), Moderate Risk (CTES 4-12), High Risk (CTES > 12), mortality and
      morbidity being 4% and 20%, 19.3% and 61.3%, 88.9% and 88.9% respectively.
      CONCLUSIONS: High risk patients may undergo a staged procedure. Moderate risk
      patients may be treated by immediate resection of the tumor, without anastomosis.
      Immediate resection and anastomosis may be reserved to low risk patients.

PMID- 14577114
TI  - [Iatrogenic lesions of the femoral vessels during hernia surgery].
AB  - The vascular lesions in hernia surgery are difficult to be found: on the basis of
      three cases personally treated and on literature data, the authors dwell upon the
      factors that influence the frequency of this event, they discuss about the
      therapeutic choices and they illustrate the short and long term prognosis.

PMID- 14577115
TI  - [Simulated used of the "grasping tie" as in esophago-jejunostomy after total
      gastrectomy].
AB  - Simulated test of effectiveness of the original tool grasping tie--technically
      already illustrated in a former paper listed in bibliography--for fixing a spongy
      rubber tube simulating an oesophagus on a circular stapler head axis, by
      tightening over it a nylon ribbon slip-knot (the tie). After connecting the head
      to the stapler anvil through an other spongy rubber tube simulating a jejunal
      loop, and the firing of the stapler, it is demonstrated the correct circular
      anastomosis achievable.

PMID- 14577116
TI  - [Isolated jejunal rupture after closed thoraco-abdominal trauma].
AB  - INTRODUCTION: Short bowel disruption following blunt abdominal trauma is rare and
      hard to diagnose and to treat. Death rate depends both on timing of surgical
      procedure and on associated lesions. MATERIAL AND METHODS: We show a case of
      short bowel isolated lesion following fall from mountain bike, III degree in
      O.I.S. Classification. Abdominopelvic US and helicoidal CT scan were performed,
      reveling pneumoperitonaeum due to hollow viscus disruption. Surgical procedure
      was performed within five hours from trauma. RESULTS: No complications occurred
      in postoperative period. Upper alimentary tract X-ray proved a regular transit,
      without any fistula. Patient was discharged on 13th day. CONCLUSION: Laparotomy
      must not be delayed if there is any doubt about bowel conditions: it's
      demonstrated that timing of surgical procedure is related to prognosis. If
      haemodynamic status of the patient allows, careful abdomen CT evaluation is
      mandatory; adequate nutritional support in postoperative period is also very
      important.

PMID- 14577117
TI  - [Hemorrhage and gastric perforation in patients with percutaneous endoscopic
      gastrostomy (PEG)].
AB  - INTRODUCTION: PEG is more and more used for those patients who need a medium and
      above all long term enteral nutrition, especially at home. This is the closest
      technical system to the requirements to have an ideal nutritional access; however
      it is burdened, on average in 32.5% of cases, with complications linked to
      technical mistakes of positioning or to a wrong management, such as haemorrhage
      and gastric perforation. CASE REPORT: A patient, subjected to supraglottic
      laryngectomy, to removal of tongue's base and to bilateral laterocervical
      lymphadenectomy and PEG carrier for 4 months, has arrived to our observation for
      a clinical outline of acute abdomen for perforation of hollow internal organ,
      preceded by progressive anaemia due to high digestive haemorrhage. Performed an
      exploratory laparotomy, it was discovered on the gastric fore face, between body
      and antrum, in proximity to the small curvature and in front of the PEG gastric
      access, a perforation with max 2 cm of diameter, crossed by probe's internal disk
      of retention. They proceeded to remove that, to unstick the gastric stoma from
      the parietal peritoneum, to suture the access of gastrostomy and the perforation
      by omentoplasty. Finally they carried out a jejunostomy for enteral feeding.
      DISCUSSION: We think we can pathogenetically identify the cause of the
      haemorrhage and of the stomach's perforation, occurred in a short time in the
      case we have examined, in the probe's movement for incorrect fixing of the plate
      of external anchorage or for excessive slimming of the patient due to not
      balanced nutritional supply, as well as in the consequent extension of its
      intraluminal part with continuous rubbing by internal disk on the gastric wall
      and with onset decubitus ulcer. Physiopathologic moments, connected with the
      supposed etiological factor, make both occurred complications as an unique
      pathologic entity, which has to be observed in the PEG carriers, in order to be
      able to diagnose it and treat it precociously and above all in order to be able
      to prevent it. Only a correct technique of positioning and of nursing and of
      management of nutritional supply is able not to thwart the finality of the PEG
      device which can be considered, in the elective indications and for the
      favourable requisites that marks it, a valid access to enteral nutrition
      realization.

PMID- 14577118
TI  - [Giant aneurysm of the splenic artery: case report and review of the literature].
AB  - INTRODUCTION: The authors describe an unusual case of giant aneurysm of the
      splenic artery. The problem of deciding between endovascular and open vascular
      surgery and what are the tools necessary to choose the most appropriate procedure
      are discussed in this report. CASE REPORT: A man 55 years old was admitted to the
      hospital for an unspecified abdominal pain. Subsequent examinations (TC and
      angiography) showed a large aneurysm of the splenic artery without any sign of
      rupture. Endovascular treatment was excluded because of the extreme tortuosity of
      the artery; the patient underwent open surgical operation of legation of the
      aneurysm and splenectomy. The patient was discharged in 6th postoperative day.
      DISCUSSION: Splenic artery aneurysm are usually an occasional finding but they
      are related with an important risk of rupture and mortality; elective treatment
      both surgical and endovascular is recommended. Emergency surgery is still
      complicated with an high rate of mortality related to the patient's
      comorbidities. Endovascular treatment by covered stent-graft or selective
      embolization may represent the best option but it can be proposed only after an
      accurate selection of the patients. Endovascular treatment also seems to be
      feasible even in emergency but only in very selected cases and in expert vascular
      interventional units. Laparoscopic surgery has been performed only sporadically.
      CONCLUSIONS: We would like to point out that nowadays the treatment of splenic
      artery aneurysm doesn't give a real choice and each case should be assessed
      singularly with the purpose to choose the best therapeutic approach either
      percutaneous or surgical.

PMID- 14577119
TI  - [Endoscopic removal of a Dormia basket impacted in the biliary tract during
      treatment of a difficult residual choledocholithiasis. Report of a case].
AB  - OBJECTIVE: The authors report their experience about the treatment of a broken
      Dormia in CBD in elder with "difficult" residual choledocholithiasis, with T
      tube. DESIGN: Report of case. Evaluation of effectiveness of endoscopic treatment
      with 2-years follow-up. SETTING: Operative Unit of General and Thoracic Surgery,
      Department of Surgical, Anatomical and Oncological Disciplines. Policlinico
      "Paolo Giaccone"--Palermo. INTERVENTION: Endoscopic removal of Dormia broken and
      impacted in CBD after 2 session of extracorporeal shock wave lithotripsy (ESWL).
      RESULTS: Resolution of the pathology with 2 session of ERCP and cholangiographic
      control. CONCLUSIONS: ERCP and ES are the gold standard in the treatment of
      choledocholithiasis. Rare complication of this method is the rupture of Dormia
      Basket in CBD: this occurrence can be solved by endoscopy, but only in well
      experienced endoscopic teams.

PMID- 14577120
TI  - Severe gastrointestinal bleeding in Crohn's disease.
AB  - INTRODUCTION: Acute gastrointestinal bleeding is rare in Crohn's disease.
      METHODS: We characterized the clinical features and course of such hemorrhage in
      patients seen at our institution from 1992 to 2000. RESULTS: Five patients had
      gastrointestinal bleeding during Crohn's disease. All patients had a known
      Crohn's disease, with a mean duration of the disease of 6 years. The source of
      bleeding was identified in four patients (80%). Endoscopy was, in all patients,
      the first diagnostic procedure. An Hartmann total colectomy with closure of the
      rectal stump and ileostomy was performed in three patients, while two patients
      with ileal massive bleeding were treated conservatively. One patient had a
      recurrence of bleeding from the small bowel one week later but he didn't required
      surgical treatment. One patient with pancolic Crohn's disease died on 10th
      postoperative day because of multiorgan failure and septic complications.
      CONCLUSIONS: Gastrointestinal bleeding is rare in Crohn's disease, with a
      predilection for site of involvement. The preoperative diagnosis of the site of
      bleeding is not easy, and enteroscopy should be mandatory in such patients.
      Surgery is required for half of cases and recurrent haemorrhage should be an
      appropriate indication for surgery.

PMID- 14577121
TI  - Traumatic rupture of nodular focal fatty infiltration of the liver: case report.
AB  - Hepatic fatty infiltration generally appears in a widespread form but it can
      occasionally involve the liver in an irregular way. As regards focal forms,
      nodular focal fatty infiltration (NFFI) has great importance regarding problems
      of differential diagnosis with benign and malignant focal pathology of the liver.
      Except for this aspect, NFFI has little clinical importance as it is mainly
      asymptomatic. We report a case of an acute bleeding of a big nodule of FFI which
      required an urgent hepatectomy.

PMID- 14577122
TI  - Teaching Czech to the international medical students: teamwork approach.
AB  - Some aspects of team teaching Medical Czech to international medical students as
      a part of the mandatory curricular subject the Czech language are discussed on
      the basis of ten years of experience with the applied pedagogical method. As the
      patient is involved in the team, principles of medical ethics are to be strictly
      observed by both the teachers and the students. In the teaching situation, the
      roles of the linguist and medical specialist are not interchangeable. The
      examination results show the normal distribution curve, but the process of
      language skills acquisition may be so far measured only by usual pedagogical
      methods without deeper knowledge of the inborn language capabilities, brain
      potential and psychological differences of individual students.

PMID- 14577123
TI  - [Acute phase proteins in female patients with breast carcinoma].
AB  - BACKGROUND: Serum levels of C-reactive protein (CRP) and orosomucoid are
      increased in more than one half of patients with metastatic breast cancer. The
      information concerning their levels in non-metastatic breast cancer is
      inconclusive. The aim of our study was to examine some acute phase proteins (CRP,
      orosomucoid, prealbumin, alpha 2-macroglobulin and transferrin) in patients with
      various clinical stages of breast cancer before hormonal and/or chemotherapy and
      3 and 12 months after its institution and to assess the influence of their levels
      on the outcome of patients. METHODS AND RESULTS: Altogether 59 women with breast
      cancer in clinical stage 0-IV, median age 62 years (47 of them after menopause)
      were examined. One patient was in stage 0, ten patients in stage I, 24 patients
      in stage IIA, 11 patients in stage IIB, five patients in stage III and eight
      patients in stage IV. Acute phase proteins (CRP, orosomucoid, transferrin,
      prealbumin and alpha 2-macroglobulin) were examined in the sera samples using
      microturbidimetry. Serum levels of CRP and orosomucoid were higher in patients
      with breast cancer in all stages compared to controls. Serum levels of CRP (resp.
      of orosomucoid) higher than mean +2 SD had 30.5% (resp. 39%) of patients with
      breast cancer. One year after the beginning of therapy serum levels of CRP and
      orosomucoid significantly decreased, however, in case of orosomucoid they remain
      higher compared to controls. Serum levels of CRP and orosomucoid correlated
      before therapy in patients with breast cancer one to another and also with serum
      levels of soluble TNF (tumour necrosis factor) receptor type I and soluble ICAM
      1. IN CONCLUSION: Patients with breast cancer before hormonal therapy and/or
      chemotherapy had compared to controls increased serum levels of CRP and
      orosomucoid, however, there was no difference between stages I-III. Observed
      correlation between serum levels of CRP and soluble TNF receptors suggests the
      important role of proinflammatory cytokines in stimulating their hepatic
      synthesis also in patients with breast cancer. Putative prognostic role of
      persistently increased levels of orosomucoid in patients with non-metastatic
      breast cancer warrants further investigation.

PMID- 14577124
TI  - [Effect of parathormone on bone blood flow in rats--possible role of NO].
AB  - Parathyroid hormone (PTH)--besides its main osteotrophic action--exerts also
      vascular effect demonstrated formerly also in bones. The aim of the presented
      work was to verify this effect of PTH using the radioactive microsphere method
      and to ascertain simultaneously whether NO does participate or not in this effect
      of PTH. We performed two experiments which were arranged in the same way, as
      follows: group I--controls, group II--PTH, group III--L-NAME, group IV--L-NAME +
      PTH. Parathyroid hormone 1.34 fragment (Sigma, USA) was administered to each
      animal 6-12 minutes before the injection of radioactive microspheres in the dose
      of 3 micrograms in the experiment A, 10 micrograms in the experiment B. NG-nitro
      L-arginin methyl ester (Sigma, USA) was given in the food for ten days before the
      experiment in the concentration of 0.025% in experiment A, 0.05% in experiment B.
      RESULTS: We present the results of experiment A in the part "Results" of the
      paper briefly in percentages--they are similar to the results of experiment B,
      but without statistical significance. Administration of PTH increased
      statistically significantly the microsphere uptake in tibia and distal femur and
      also the blood flow in both bones, increased the cardiac output and lowered blood
      pressure. Administration of L-NAME alone induced decrease of the heart rate only.
      After the injection of PTH to the rats fed L-NAME there was--compared to the
      injection of PTH only--the blood flow through both bones significantly lower. The
      observed increase in the bone blood flow as well as changes in the general
      circulation show that i.v. injection of PTH under the experimental conditions
      used does induce vasodilatation in female rats. Influence of these changes by the
      administration of L-NAME indicates possible participation of the nitric oxide
      (NO) in the observed effect of PTH on the vessles.

PMID- 14577125
TI  - Severe late complication of appendicitis. Case report.
AB  - BACKGROUND: Diffuse necrotizing soft-tissue infections are severe due to their
      rapid progression; there is a vital need for settling proper early diagnosis. The
      task of the clinician is mainly in distinguishing localized infection from the
      diffuse process. CASE PRESENTATION: In our case report we demonstrate a 32 yr old
      man with a curious development of severe necrotizing infection of submucosis with
      gas production as a conclusion of perforation of Schloffer's tumour, which
      developed after appendectomy carried 20 years ago. CONCLUSIONS: In case of
      diffuse necrotizing soft-tissue infections only immediate surgical revision can
      confirm initial stages of severe forms of infection.

PMID- 14577126
TI  - Role of zinc in eukaryotic cells, zinc transporters and zinc-containing proteins.
      Review article.
AB  - As a catalytic and/or structural cofactor for countless of zinc-dependent enzymes
      and proteins, zinc is an essential element for all organisms. This review
      summarizes the basics of human zinc physiology and biochemistry. The role of zinc
      in the regulation of gene expression and cellular signal transmission is
      described in more details. The present explosive growth of new knowledge about
      various biological roles of zinc will undoubtedly lead to the future development
      of new powerful drugs and to treatment of many diseases including cancer.

PMID- 14577127
TI  - Molecular basis of Diamond-Blackfan anaemia: what have we learnt so far? Review
      article.
AB  - A considerable progress has been made in the last three years in the uncovering
      of the molecular basis of Diamond-Blackfan anaemia (DBA). Two genetic loci on
      19q13.2 and 8p23 chromosomes have been associated with the DBA phenotype, and the
      ribosomal protein S19 (RP S19) located at 19q has been found mutated in 25% of
      DBA patients. In this review we will outline possible mechanisms of how mutations
      in RP S19 might lead to the DBA phenotype, we will discuss candidate genes on
      8p23 chromosome, and finally, a complex molecular model of DBA development will
      be proposed.

PMID- 14577128
TI  - The interaction and functional properties of leukocyte molecules of human
      leukemia/lymphoma cells.
AB  - The expression of 82 cell surface molecules was analysed on pathological cells
      from 52 patients with acute lymphoblastic leukemia (T and B), acute myeloid
      leukemia (FAB: M0, M1, M2, M3, M4, M5), chronic myeloid leukemia, chronic myelo
      monocytic leukemia) and non Hodgkin's lymphoma (T and B types). We have selected
      patients with a high leukocyte count and percentage of blasts. Staining for
      membrane molecules was done by the immunofluorescence method and evaluated by
      flow cytometry. The findings indicate that expression of membrane molecules on
      pathological cells is quantitatively and qualitatively different in individual
      cases. The leukemia/lymphoma cells in their crude from represent the main
      phenotypes of normal haematopoietic cells, which reveal the great diversity of
      immunophenotypes within the main functional characterization of blood
      malignancies. The immunophenotype heterogeneity of leukemic cells has proved to
      be much greater than the match with existing classification criteria, this fact
      could raise the necessity for further functional evaluation and specification of
      immunophenotyping of the leukemia/lymphoma cells. The concept of explanation of
      pathogenesis and pathophysiology of different types of leukemia/lymphoma cells on
      the basis that they are derived from normal haematopoiesis must be accepted,
      because the number of membrane markers and their functional properties are
      correspondingly convincing.

PMID- 14577129
TI  - Nucleolar abnormalities--a defect of the nucleolar preribosome assembly--in
      ringed sideroblasts in refractory anaemia with ringed sideroblasts (RARS) of
      myelodysplastic syndrome (MDS). An electron microscopic study.
AB  - Ringed sideroblasts were studied by means of transmission electron microscopy in
      patients suffering from refractory anaemia with ringed sideroblasts (RARS) of
      myelodysplastic syndrome (MDS) to provide more information on the structural
      organization of nucleoli in these abnormal erythroblasts. For control of the
      electron microscopic observations nucleoli in erythroblasts were also visualized
      by two widely used cytochemical procedures for the demonstration of RNA and AgNOR
      proteins. In contrast to previously described ultrastructure of nucleoli in
      "normal" erythroblasts, nucleoli of ringed erythroblasts in RARS of MDS were
      frequently characterized by a reduced incidence or lack of dense ribonucleic acid
      (RNA) containing granular components. Since the dense RNA containing granular
      components represent preribosomes, such sideroblasts in RARS of MDS exhibit a
      further nucleolar abnormality, which reflects a severe alteration of the
      nucleolar ribosome assembly in these abnormal cells. On the other hand, the
      alteration of the preribosome assembly was not noted in early developmental
      stages of ringed sideroblasts such as proerythroblasts. In addition, nucleoli in
      advanced or terminal stages of few ringed sideroblasts also did not exhibit such
      nucleolar abnormality and thus confirm a great structural and functional
      variability of these cells. The defect of RNA containing structures in nucleoli
      of advanced and terminal stages of erythroblasts are in a hormony with the light
      microscopic cytochemistry, which demonstrated a significantly smaller incidence
      of micronucleoli in specimens stained for RNA than in those stained for AgNOR
      (silver stained nucleolus organizer region) proteins.

PMID- 14577130
TI  - Long-term follow-up of chimerical state of the patients transplanted for
      different haematologic diseases.
AB  - Long-term follow-up of peripheral cellular chimerism in patients treated with BMT
      or PBSCT revealed the usefulness of their continuous monitoring at molecular
      level. Our results are based on monitoring of 120 patients, who were followed for
      at least 24 months. Comparison of the patients treated for chronic myelogenous
      leukemia (CML), acute myelocytic leukemia (AML), acute lymphocytic leukemia
      (ALL), myelodysplastic syndromes (MDS) and aplastic anaemia (AA) revealed that
      mixed chimerism was practically absent in MDS and relatively long-lasting in ALL
      and AA (regardless to substantially different post-transplantation treatment).
      The first disease relapses signalized by molecular checking of mixed peripheral
      chimerism were observed also after a period of remission lasting for several
      years. Molecular watching enables us to detect relapses at their very beginning
      that would remain hidden to less sensitive methods. We believe that all of the
      transplanted patients ought to be monitored for residual disease i.e. cellular
      chimerism using molecular methods without time limits. On the other hand low
      level of mixed cellular chimerism is not necessarily a sign of disease
      progression and can remain unchanged as "status quo" for a very long period.

PMID- 14577131
TI  - On the way to functional genomics.
AB  - Proteomics, the global comprehensive analysis of cellular proteins, will
      contribute to our understanding of gene function in the post-genomic era. The
      strategies of proteome analysis include the protein expression proteomics dealing
      with the comparison of cellular or tissue protein levels in the control and
      affected state (e.g. in the disease) and cell mapping proteomics aimed to define
      protein-protein interactions that constitute intracellular signalling network.
      The currently used methods of proteome analysis represent two-dimensional gel
      electrophoresis for protein separation, the image analysis means for protein maps
      comparison and the mass spectrometry (MALDI-TOF, MALDI-ESI) and bioinformatics
      means (sequence databases) for protein identification. For the protein
      interaction studies the yeast two-hybrid system is mostly employed. New concepts
      of disease diagnosis and treatment as well as new drugs design can be envisioned
      from the proteomic analysis.

PMID- 14577132
TI  - Image analysis of blood platelets adhesion.
AB  - Adhesion of blood platelets is one of the major events in haemostatic and
      thrombotic processes. We studied adhesion of blood platelets on fibrinogen and
      fibrin dimer sorbed on solid support material (glass, polystyrene). Adhesion was
      carried on under static and dynamic conditions and measured as percentage of the
      surface covered with platelets. Within a range of platelet counts in normal and
      in thrombocytopenic blood we observed a very significant decrease in platelet
      adhesion on fibrin dimer with bounded active thrombin with decreasing platelet
      count. Our results show the imperative use of platelet poor blood preparations as
      control samples in experiments with thrombocytopenic blood. Experiments carried
      on adhesive surfaces sorbed on polystyrene showed lower relative inaccuracy than
      on glass. Markedly different behaviour of platelets adhered on the same adhesive
      surface, which differed only in support material (glass or polystyrene) suggest
      that adhesion and mainly spreading of platelets depends on physical quality of
      the surface. While on polystyrene there were no significant differences between
      fibrin dimer and fibrinogen, adhesion measured on glass support material markedly
      differed between fibrin dimer and fibrinogen. We compared two methods of
      thresholding in image analysis of adhered platelets. Results obtained by image
      analysis of spreaded platelets showed higher relative inaccuracy than results
      obtained by image analysis of platelets centres and aggregates.

PMID- 14577133
TI  - Hemostyptic effect of oxidized cellulose on blood platelets.
AB  - Cellulose is one of the hemostyptic biomaterials, which are able to initiate or
      accelerate blood coagulation at the site of their application. It belongs to
      surgical sealants. The mechanism of its action is not clearly understood. We
      studied the participation of blood platelets in this mechanism. As a marker of
      platelet activation we used serotonin release reaction. Serotonin release in
      platelet rich plasma incubated with various concentrations of oxidized cellulose
      (0.5%-2.0%) started in about 20 min. Washed platelets were not directly activated
      by oxidized cellulose within one hour. Washed platelets reconstituted in plasma
      obtained from two patients with coagulation factor XII deficiency were activated
      by oxidized cellulose with a prolonged lag phase. Our results demonstrate the
      significant influence of factor XII on blood platelets activation by oxidized
      cellulose.

PMID- 14577134
TI  - Laboratory tests for precise classification and genetic analysis of von
      Willebrand disease.
AB  - von Willebrand disease (vWD) is the most common inherited bleeding disorder,
      which is highly heterogeneous ranging from asymptomatic laboratory abnormality to
      a life threatening bleeding. The condition is caused by a quantitative or
      qualitative deficiency of von Willebrand factor (vWF). Since 1994 it has been
      classified into six subgroups based on evaluation of the vWF level and function.
      Correct classification of vWD is required for its optimal management. vWD is
      inherited as a dominant or recessive trait linked to the vWF gene. However, the
      inheritance of type 1 vWD is not always linked to the vWF gene and novel
      modifying genes are expected to play a significant role in the type 1
      pathophysiology. Laboratory tests required for correct type classification and
      for genetic analysis have long been awaited in Czech Republic. The purpose of
      this report is to inform about discriminatory and genetic tests recently made
      available at the Institute of Haematology and Blood transfusion.

PMID- 14577135
TI  - Complete proteinogram of cerebrospinal fluid and its contribution to the
      diagnostics of inflammatory and autoimmune diseases of the central nervous
      system.
AB  - Complete evaluation of cerebrospinal fluid proteinogram represents a routine
      request of the clinician in the analysis of CSF in the Czech Republic. It
      comprises the measurement of concentrations of acute phase proteins (CRP,
      orosomucoid, haptoglobin, transferrin, prealbumin), immunoglobulins (IgG, IgA,
      IgM), compressive markers (albumin, fibrinogen), markers of CNS tissue
      destruction (apolipoproteins A-I, A-II, Apo B), complement components (C3, C4),
      alpha-1-microglobulin, beta-2-microglobulin, and proteinase inhibitors (alpha-1
      antitrypsin, antithrombin III). Therefore, 19 CSF proteins of precisely verified
      clinical relevance are routine parameters for the assessment of the functional
      state of the blood-CSF barrier, presence of the intrathecal synthesis of
      immunoglobulins, inflammatory changes and verification of CNS tissue destruction.
      Evidence of these clinically relevant and independent parameters enabled the
      detection of the presence of autoimmune and neuroinfective diseases of CNS, even
      in clinical cases where the basic CSF parameters do not express relevant changes,
      or they are of a bordering or non-specific character. Clinically typical and the
      most significant abnormalities in the CSF proteinogram represent themselves a new
      access to a contemporary CSF analysis. Despite the fact that assessment of CSF
      proteins and their analysis is quite a difficult field in laboratory medicine, it
      is now routinely requested and routinely performed in the Czech Republic.

PMID- 14577136
TI  - Volumetry of striatum and pallidum in man--anatomy, cytoarchitecture,
      connections, MRI and aging.
AB  - BACKGROUND: For comparing of the pathological and normal healthy state it is
      essential to obtain sufficient amount of the volumetric data. Nevertheless most
      of the publicized works use only few healthy controls opposite to the patients
      for the measuring of the basal ganglia volume. Further essential condition is to
      take into account the effect of age to the basal ganglia volume in such analysis.
      PURPOSE: The goal of our study was (1) to give the current review of the
      structure, neurotransmitters, connections and general integration of the basal
      ganglia in the pathways of the central nervous system, (2) aggregate sufficient
      amount of volumetric data by virtue of MRI and post-mortem studies, and appoint
      volumes of the striatum and pallidum, (3) evaluate aging of these structures in
      adult healthy patients. Another goal was (4) to inspect the correlations between
      the size of the basal ganglia and volume characteristics of the brain, cranial
      capacity or frequently measured dimensions within CNS. In the spite of the fact
      that it is not possible to measure all of these dimensions for clinicians who
      want to determine if the structure is "normal" or not. Another goal was (5) to
      find a simple measure, which could serve as the indicator of the real size of
      structure of the interest. METHODS: By virtue of the classical anatomical methods
      and MRI examination we appointed volumes of the striatum (furthermore divided
      into the complex of the caudatum--nucleus accumbens--CD-Acc and putamen) and
      pallidum in the sample of 108 healthy adults (18-89 years old). From another
      measurements we calculated the cranial capacity and volume characteristics of
      each brain. RESULTS: In a general view that does not respect changes due to age
      neither volumetric difference between two sexes nor interhemispheric difference
      was significant for absolute volumes of the striatum, CD-Acc complex, putamen and
      pallidum. In the case of the striatum, significant correlation between size and
      age was found (p < 0.0001) for absolute volumes in both sexes. In men, striatum
      showed a decrease about 14.3% in volume in the 20-50-year age range (about 4.8%
      per decade). In woman, the age related shrinkage is about 16.9% (about 5.6% per
      decade). Dependence on age was not statistically proven for volume of female
      complex CD-Acc (p = 0.061). Age related decrease of female putamen was about
      23.15% in the 20-50 year age range (7.7% per decade). In men, the seizure
      decrease of the caudate--accumbens complex amounts 16.2%, in the same age range
      (5.4% per decade). Similarly, volume of the putamen in men decreases up to 12.3%
      between 20-50 years of age (4.1% per decade). In men, the pallidum showed a
      decrease about 21.6% in volume in the 20-50-year age range (7.2% per decade). In
      women, it amounts only 11.5% (3.8% per decade). Plane of the striatum in the
      level of the commissura anterior showed high correlation with total striatal
      volume (p < 0.0001, r = 0.668). The percentual portion of striatal volume at the
      level of the commissura anterior (1 cm thick slice) does not differ statistically
      between males and females. In our data it gives 28.56% (SD = 3.05). Correlation
      between the striatal planes and age was significant in both sexes (in women: p =
      0.007, r = 0.348, and in men: p = 0.029, r = 0.349) as in the case of the
      correlation between striatal volume and age. CONCLUSIONS: Our findings suggest
      that age mirror differently on separate structures in the brain. We have found
      unequal volume decrease within both sexes even particular nuclei. Our findings
      also suggest that decrease of the basal ganglia volume in the dependence on age
      is not linear but it is composed from periods without changes and periods with
      reduction of its size. In the case of the striatum, behaviour of changes looks
      similar (with only 5 years), while in the case of the pallidum this situation is
      markedly different. Our observations may suggest intersexual singularity in the
      aging of brain structures. From one MRI, from one frontal slice in the level of
      the commissura anterior is possible to reduce total volume of the striatum for
      every examined individual. Simple graph shows interval, where the normal value of
      this plain should be in dependency on age and sex of the examined patient.
      Another graph allows reducing from this plane the total volume of the striatum.
      These findings can be the quick and reliable aid in better diagnostics of
      different diseases.

PMID- 14577137
TI  - Anomalous maxillary lateral incisor--the only product of dental lamina, difficult
      classifiable in the time. Symptom of hypodontia syndrome non-described until
      present time.
AB  - The authors described anomalous development of maxillary lateral incisor non-yet
      published in stomatologic literature. Diagnostics and clinical findings of the
      anomaly and the prognosis of the affected tooth they based on the description of
      six longitudinal observed patients. The principal symptom of the anomaly is the
      disturbance of time-plan of the tooth development. Terms of the tooth
      mineralization, the time of eruption and root completion cannot be included
      either in deciduous or in permanent dentition. The tooth is the only product of
      the dental lamina; it has no predecessor or successor. Frequent disturbances of
      the eruption pathway result often in anomalous position of the tooth. Taking into
      consideration the fact that the anomaly appeared always in connection with
      hypodontia syndrome, it is possible to consider it to be the symptom of
      hypodontia syndrome. This fact is more significant as it enables to establish the
      diagnosis of hypodontia syndrome already in early deciduous dentition.

PMID- 14577138
TI  - The role of specific CD4+ T helper cell response in the course of hepatitis C
      virus infection.
AB  - Changes in the specific CD4+ T-cell immunity against HCV in response to the
      treatment with alpha-interferon and ribavirin have been studied in 56 patients
      with chronic HCV infection. It was shown that after the treatment enhancement of
      the immune response to HCV infection was mainly due to the elevation of the
      numbers of NS3 and NS4 antigen-specific CD4+ T cells, which indicates that these
      cells play an important role in the development of the specific defense directed
      towards elimination of the virus from the human organism.

PMID- 14577139
TI  - [Fibrillary glomerulonephritis].
AB  - An overview of fibrillary glomerulonephritis (GN) is given as well as the
      description of clinical course in four patients diagnosed and treated in our
      department. Fibrillary GN and immunotactoid glomerulopathy are entities,
      characterized by fibrillar and microtubular deposits in mesangium and the
      glomerular capillary loops. Decisive for diagnosis of fibrillary GN (resp.
      immunotactoid GN) remains the electron microscopy (EM) of the renal biopsy (RB)
      specimen. At the nephrologic division of 1st Internal Department of 1st Medical
      School of Charles University four cases of patients with fibrillary GN were
      diagnosed from the mid seventies (when both entities were newly described) by the
      end of the year 2001. In all patients the diagnosis was proven by EM. RB was
      indicated mainly for proteinuria, hematuria and decrease of renal function. On
      conclusion: though fibrillary GN/immunotactoid GN are relatively rare disorders,
      they represent entities, which should not be omitted in the differential
      diagnosis of nephrotic syndrome/renal insufficiency and which deserve further
      study.

PMID- 14577140
TI  - [Levels of advanced oxidation protein products (AOPP) in the first trimester of
      pregnancy].
AB  - Advanced oxidation protein products (AOPP) may be sensitive biomarkers for
      protein damage mediated by reactive oxygen species. AOPP were measured in the
      serum of 41 pregnant women in the 8th-12th week of pregnancy. Parameters of
      prenatal screening in the first trimester (pregnancy-associated plasma protein A-
      PAPP-A and free beta human chorionic gonadotrophin--free beta HCG) and
      anticardiolipin antibodies (ACA) IgG and IgM were determined as well. A group of
      healthy blood donors--women and men was used for comparison. AOPP were determined
      spectrophotometrically according to Witko-Sarsat [24] (absorbance at 340 nm) and
      were expressed in chloramine units (mumol/l). Other analytes were determined by
      immunoanalytic methods. AOPP levels in pregnant women in the first trimester are
      significantly higher in comparison with blood donors--women (89.46 +/- 33.38
      mumol/l vs 57.34 +/- 16.31 mumol/l, p < 0.0001) but there is no statistically
      significant difference between pregnant women and blood donors--men (89.46 +/-
      33.38 mumol/l vs 78.60 +/- 44.01 mumol/l). AOPP level does not correlate either
      with the age of pregnant women or with the parameters of prenatal screening and
      ACA IgG and IgM. Higher levels of AOPP in the serum of pregnant women in
      comparison with women--blood donors may reflect an increase of oxidative stress
      in pregnancy.

PMID- 14577141
TI  - [Role of IGF-I and NO on regulation of regional blood circulation in the bones of
      rats].
AB  - We present the results of two experiments aimed at the role of IGF-I and NO in
      the regulation of bone blood flow. In the first experiment A we determined the
      blood circulation in tibia and distal part of femur and the blood level of IGF-I
      after oophorectomy (OOX, 4 weeks before the experiment) and/or administration of
      NG-nitro-L-arginin methyl ester (L-NAME, Sigma, USA, 0.05% in the food for 10
      days before the experiment). In the second experiment B we checked up the
      possibility of correlation between the bone blood flow and IGF-I level in female
      rats control and after the administration of estradiol (Agofollin Depot, Biotika,
      Slovak Republic, 1 mg s.c., two times weekly, for 4 weeks before the experiment).
      The bone blood flow was ascertained by means of 85-Sr microsphere (NEN, USA)
      technique, IGF level was estimated with Rat IGF-I RIA kit (DSL, USA). RESULTS:
      Experiment A: group I: controls--sham operation, group II: oophorectomy (OOX),
      group III: L-NAME + sham operation, group IV: OOX + L-NAME. OOX elevated the 85
      Sr microsphere uptake and bone blood flow in tibia and distal femur. The
      administration of L-NAME to non-castrated females lowered significantly the blood
      flow in the femur only, whereas in OOX females it inhibited completely the usual
      OOX-induced increase in circulatory indicators in both bones. IGF-I level was
      higher after OOX, administration of L-NAME did not exert any effect on it.
      Experiment B: group I: control females, group II: estradiol. After the
      administration of estradiol, there was marked decrease in the uptake of 85-Sr
      microspheres and blood flow in both bones, decrease in body weight, cardiac
      output, heart rate, blood pressure and also in the blood level of IGF-I. Density
      and ash weight of the tibia were elevated. Important results found in the group I
      of experiment B seem to be the correlations between the blood level of IGF-I and
      85-Sr microsphere uptake in tibia (r = 0.68, p < 0.01), between IGF-I and blood
      flow in tibia (r = 0.54, p < 0.05) and between IGF-I and 85-Sr microsphere uptake
      in distal femur (r = 0.55, p < 0.05). However, in the group II of females after
      estradiol no significant dependence could be demonstrated. The results support
      the conception of the role of IGF-I and NO in the regulation of local blood flow
      also in the bones of rats. The possible sequence of the interrelations could be
      as follows: OOX--increase in the blood level of IGF-I--increase in the production
      of NO--vasodilatation and increase in the bone blood flow. Significant
      correlations between the blood level of IGF-I and bone blood flow represent
      further evidence of the participation of IGF-I in the regulation of bone blood
      flow in rats.

PMID- 14577142
TI  - Civil rights enforcement in the modern healthcare system: reinvigorating the role
      of the federal government in the aftermath of Alexander v. Sandoval.

PMID- 14577143
TI  - Sex & gender: the politics, policy, and practice of medical research.

PMID- 14577144
TI  - Advocating for a Medicare prescription drug benefit.

PMID- 14577145
TI  - The responsibility of research universities to promote access to essential
      medicines.

PMID- 14577146
TI  - The role of university technology transfer operations in assuring access to
      medicines and vaccines in developing countries.

PMID- 14577147
TI  - [Interferon-induced 2',5'-oligoadenylate system: key components and biological
      functions].
AB  - The current data about the 2',5'-oligoadenylate system is reviewed. Its role in
      interferon signaling and cell metabolism regulation is discussed. The interferon
      system is known to be characterized by a wide range of biological functions such
      as antiviral defense, control of cell growth and differentiation, oncogenic
      stability, apoptosis, immune activation, etc. The biological role of interferon
      that is the multifunctional cytokine is discussed more in detail. The structure
      of main components of interferon signal transduction cascade (2',5'
      oligoadenylate, 2',5'-oligoadenylate-synthetase and ribonuclease L) is reviewed.
      The interferon-induced 2',5'-oligoadenylate system is considered as the component
      of common regulatory system coordinating cell metabolism.

PMID- 14577149
TI  - [Methods and prospects of development of the affinitive sorbents for plasminogen
      isolation from human blood plasma].
AB  - The review paper was dedicated to development of the promising photochemical
      synthesis of affine sorbents for plasminogen isolation from the human blood
      plasma. Some most interesting, from the viewpoint of practice, types of sorbents
      and carriers based on high-molecular compounds of natural (organic) or synthetic
      origin have been considered. The advantages of the use of photochemical synthesis
      of biospheric sorbent as compared with thermochemical method have been shown. The
      most promising methods of creation of affine sorbents on the basis of oligomer
      polymeric photoinitiators and oligomerpolymeric photosensibilizing (donor
      acceptor) systems are presented.

PMID- 14577148
TI  - [Enzymes of snake venoms].
AB  - Snakes' venom is a mixture of biologically active substances, containing proteins
      and peptides. A number of these proteins interact with haemostasis system
      components. Activators and inhibitors affecting blood coagulation and
      fibrinolysis systems are of special interest. Venom components can be classified
      into three main groups, such as procoagulants, anticoagulants and fibrinolytic
      enzymes according to their action. This review is focused on enzymes from
      Agkistrodon halys halys venom. They are thrombine-like enzyme, named Ancystron-H,
      flbrinogenolytic enzyme, protein C activator and platelet aggregation inhibitor.
      Ancystron-H is used for determination of fibrinogen level in blood plasma of
      patients undergoing heparin treatment and blood coagulation inhibitors
      accumulation. The fibrinogenolytic enzyme can be used as the instrument for
      protein-protein interactions in fibrinogen-fibrin system. The protein C activator
      is used for protein C level determination in blood plasma with different
      pathologies. Functions of the platelet aggregation inhibitor, belonging to
      disintegrins group, can be used for development of antithrombotic preparations.
      Information about the use of snake venoms in science and medicine is presented.

PMID- 14577150
TI  - [Effect of temperature on structure and functional properties of horseradish
      peroxidase].
AB  - The dynamics of structural and functional changes proceeding in a peroxidase
      molecule under the effect of temperature was studied. It was shown that
      peroxidase thermoinactivation proceeds in two consequent stages. Based on the
      analysis of enzyme peroxidase and oxidase activity and peroxidase spectral and
      buffer characteristics, it was established that at temperatures from 20 to 55
      degrees C reversible conformation there occur changes of the hemoprotein molecule
      related to consequent unfolding and folding of the protein globule. The influence
      of temperature of 60 degrees C and above induces the protein globule unfolding
      and loosing of peroxidase activity.

PMID- 14577151
TI  - [Effect of eosin Y on Ca2+, Mg2+-ATPase of the smooth muscle sarcolemma].
AB  - Eosin Y was studied with the aim to elucidate the mechanism of its inhibitory
      effect on the activity of Ca(2+)-transporting ATPase of myometrium cell plasma
      membrane. The inhibitor was studied for its effect on the maximal rate of the ATP
      hydrolase reaction catalyzed by Ca2+, Mg(2+)-ATPase, on the enzyme affinity for
      the substrate and a possibility of enzyme activity protection under the inhibitor
      effect by the main reagents of ATP-hydrolase reaction. It was established that
      eosin Y decreased the turnover rate of this enzyme and his affinity for ATP.
      Preincubation of ATPase with ATP (or ATP plus MgCl2) had no effect on the extent
      of enzyme inhibition by eosin Y. This result proves that eosin Y and ATP do not
      compete for the site of binding on the enzyme.

PMID- 14577152
TI  - [Effect of sodium nitroprusside on Na+, K+-ATPase of rat myocardium and renal
      cortex].
AB  - The influence of NO donor, sodium nitroprusside (SNP) in concentrations of 10(-5)
      10(-3) M, on the Na-pump activity in membrane preparations (microsomes) of rat
      miocardium and renal cortex was studied. A correlation has been observed between
      Na-pump activation by 31.4% and 73.6% and increase in thiol group content by
      45.0% and 94.0% in native microsomes of myocardium and renal cortex by low
      concentrations of SNP (10(-5)-10(-4) M). The Na-pump activation as well as the
      increase in the number of DTNB-reactive thiol groups was abolished after the
      detergent treatment (0.025% sodium dodecylsulphate); however, the detergent by
      itself exerted similar influence on Na-pump activity and thiol group content in
      microsomes. A comparable effect of other oxidants (hydrogen peroxide and
      nitroglycerine) on SH-group content in microsomes of renal cortex was also shown.
      A conclusion was made that non-specific oxidative action of SNP on some membrane
      structures in microsome preparations led to their exposure and activation of the
      Na-pump by demasking of its latent activity.

PMID- 14577153
TI  - [Effect of polyamines on actomyosine-ATP-ase activity in smooth muscles of the
      uterus].
AB  - The ability of the aliphatic polyamines to inhibit [figure: see text] the ATPase
      activity of smooth muscle actomyosine satisfies the succession: spermine >
      spermidine > putrescine that is correlated with magnitude of positive charge at
      physiological value of pH. The most effective inhibitor of the ATP hydrolysis
      process is the spermine, which highest inhibitory action is manifested at 10(-3)
      M concentration, in lesser concentration (10(-5) M) activates the actomyosine
      ATPase. While defining the kinetic parameters of the ATP hydrolysis reaction
      catalyzed by uterus myometrium the correlation between inhibiting the ATPase
      activity of myometrium contractile complex under introduction into the incubation
      medium of 10(-3) M spermine and decreasing the affinity of actomyosine for ATP
      was made; the activating effect of spermine on ATPase activity of actomyosine
      complex in the presence of 10(-5) M spermine correlated with the increase of
      actomyosine affinity for Mg2+.

PMID- 14577154
TI  - [Use of 1- and 2-thionaphthylacetates as cholinesterase substrates].
AB  - 1- and 2-thionaphthylacetates were tested as cholinesterase substrates. It was
      shown that the butyrilcholinesterase from horse serum can hydrolize these
      compounds. The hydrolysis velocity of 1-thionaphthylacetate was comparable with
      hydrolysis velocity of acetylthiocholine (the well known cholinesterase
      substrate), but 2-thionaphthylacetate was hydrolysed more slowly. The values of
      the kinetic parameters V and K(m) for butyrylcholinesterase hydrolysis of 1- and
      2-thionaphthylacetates were determined. It was offered to use 1
      thionaphthylacetates as the substrate for cholinesterases.

PMID- 14577155
TI  - [Catalytic characteristics of 5'-nucleotidase in the structure of cell membrane
      rafts in smooth muscles].
AB  - 5'-nucleotidase (EN 3.1.3.5) is widely distributed enzyme occurring in
      vertebrate, bacterial and plant cells. The main physiological function of 5'
      nucleotidase is hydrolysis of 5'-AMP to adenosine and Pi. It was found that the
      detergent-insoluble membrane domains (rafts) are enriched by proteins possessing
      high 5'-AMPase activity. This study is aimed to investigate some physical and
      chemical properties of 5'-nucleotidase, which is present in detergent insoluble
      membrane domains isolated from pig stomach and lung. It was shown for the first
      time that catalytic properties of the raft-associated 5'-nucleotidase and of the
      pure enzyme described in literature differ. Our results demonstrate that the
      greatest activity of the raft-associated enzyme takes place in the physiological
      conditions contrary to the pure enzyme. Our data suggest that such changes of 5'
      nucleotidase catalytic activity might be due to the disruption of its interaction
      with membrane rafts.

PMID- 14577156
TI  - [Role of extra- and intracellular Ca2+ in changes of NO2- and H2O2 production by
      endometrium].
AB  - The work is aimed to find out the role of extra- and intracellular Ca2+ in cyclic
      mechanisms of NO2- and H2O2 metabolism in the stroma cells of endometrium
      activated by acetylcholine. High activity of Mg2+, Ca(2+)-ATP-ase is
      characteristic of stroma cells of the endometrium. This activity is tested in the
      presence of 0.01% of the Triton X-100 (36 +/- +/- 2 mumole Pi/mg of protein for 1
      hour). The acetylcholinesterase activity in these systems is equal to 9.8 +/- 0.2
      mumole thiocholinebromide/mg of protein for 1 hour. Acetylcholine (10 microM)
      elevated essentially the concentration of cytosolic Ca2+ in them. It was
      established, that in the control the suspension of stroma cells produced 1
      nmol/NO2-/10(6) of cells, this value being constant for the experimental period
      of time in the range of 5-60 s. The activation of cells (1 microM acetylcholine +
      10 microM Ca2+) results in the appearance of cyclicity (maxima on 5, 15 and 60 s)
      and 5-fold intensification of NO2- production. The rise of extracellular
      concentration of Ca2+ up to 0.1-1--10 mM results in essential change of the
      character of the time dependence of NO2- metabolism and only in inappreciable
      intensification of the response amplitude. Such a pattern is observed for H2O2:
      0.77 mumol H2O2/10(6) of cells in the control, at 10 microM Ca2+ maxima of
      production on the 5 and 30 s, change of the form of the time response, instead of
      the amplitude under the increase of concentration of extracellular Ca2+.
      Preincubation of cells with modifiers endoplasmic reticulum ryanodine, caffeine
      (1 mM) and heparine (10 mM) results in essential drop of NO2- production and
      infringement of cyclicity, the effect of ryanodine being more expressed on 5 s,
      than on 15 s, and heparine--also on 5 s, and on 15 s. Preincubation of cells with
      methylene blue (10 mM), which inhibits guanilate cyclase, result in considerable
      intensification of NO2- and H2O2 formation and cyclicity losses. Dynamics of NO2-
      formation (is controversy) reciprocated with cGMP, whereas nitrosoglutathione
      production and NO3- tends to saturation in the course of time. Thus,
      acetylcholine-dependent variations of NO2- and H2O2 concentrations in the
      suspension of stroma cells depend on the state of extra- and intracellular Ca(2+)
      stores, are controlled by cGMP. It may be assumed, that the NO2- production
      minima are caused by its transfer in NO3- and its binding with glutathione.

PMID- 14577157
TI  - [Effect of ADP and GroES on interaction of molecular chaperonin GroEL with non
      native lysozyme].
AB  - The interaction of the molecular chaperonin GroEL with fluorescein-labeled
      lysozyme in the presence of high concentrations of thiol reagent--dithiothreitol
      (DTT) has been studied. In case of high concentrations of DTT lysozyme loses the
      native conformation due to the disruption of the intramolecular disulfide bonds
      stabilizing its structure and effectively aggregates. It has been shown that in
      the presence of high concentrations of DTT and two-fold molar excess of GroEL the
      lysozyme tightly interacts with GroEL that essentially decreases the efficiency
      of its aggregation. The addition of ADP to the complex of GroEL with nonnative
      lysozyme noticeably decreases the interaction of the chaperonin with nonnative
      protein target resulting in some increase of the efficiency of its aggregation.
      However, the addition of the co-chaperonin GroES together with ADP (i.e. the
      formation of the complex of GroEL with GroES) leads to drastic weakness of the
      interaction of GroEL with nonnative lysozyme and the efficiency of its
      aggregation becomes comparable with that in the absence of GroEL.

PMID- 14577158
TI  - [Effect of colloid gold on physiologic-biochemical processes in Escherichia coli
      1257].
AB  - The influence of colloid gold on the growth processes, ATP-ase activity and
      extrusion of protons in Escherichia coli 1257 was studied. The particles of
      colloid gold exert nonmonotonous influence on these processes with different
      direction is such a way that small concentration of this metal (5 x 10(-7)-5 x
      10(-6) mg/ml) exert stimulative effect, while higher concentrations of colloid
      gold result in the suppression of biological activity of the bacterial cells. The
      discovered peculiarities of colloid gold influence of E. coli strain may be
      determined by specificity of contact interaction of metal particles with the
      surface of bacterial cells.

PMID- 14577159
TI  - [Effect of mycotoxin T-2 on bioluminescence intensity of bacteria].
AB  - The acute and chronic toxicity of T-2 was studied by bioluminescent method with
      the use of two strains of luminous bacteria--P. phosphorum Sq3 u V. fischeri F1
      as biological objects. It was shown that in acute experiments after 10 min
      incubation of bacteria in the presence of T-2 the bioluminescence inhibition on
      the 50% level was observed at the toxin concentration equal to 12 mg/mL. In
      chronic experiments such a level of bioluminescence inhibition was registered
      after 16 hours incubation at the toxin concentration of 18 mg/mL. T-2 toxicity
      was also investigated in the presence of different serum albumin concentrations.
      It decreases with the increase of albumin concentration at the short term of
      incubation (5 min) of the mixture to be analyzed. In case of the longer term of
      incubation (up to 30 min) of this mixture T-2 toxicity was restored. Probably, it
      is a result of destruction of protein-toxin complex, which is, evidently,
      reversible and may be characterized by some index. It is necessary to emphasize
      that the sensitivity of T-2 analysis increases under the decrease of pH value up
      to lower bacterial physiological level, i.e. to 5-5.5. The revealed abilities of
      T-2 toxin effect on the intensity of bacterial bioluminescence may be used under
      the development of instrumental analytical approach on the basis of biosensor
      technology for testing this toxin in the environment. Taking into account the
      analysis simplicity and rapidity, such analytical device may have a perspective
      for wide practical application.

PMID- 14577160
TI  - [Complement-binding and immuno-modulating properties of polyreactive
      immunoglobulins].
AB  - New data concerning biological properties of polyreactive immunoglobulins (PRIG)
      were obtained as a result of treatment of mouse serum immunoglobulins by 4 M KSCN
      and are presented in the paper. In particular, the capacity of PRIG to bind C1q,
      the subunit of the first component of complement was studied. It was shown that
      PRIG's binding capacity to C1q is similar to that of intact immunoglobulins.
      Intravenous administration of PRIG into mice together with either sheep red blood
      cells or heat-inactivated staphylococcal bacteria did not affect the immune
      response to these antigens. Meanwhile, the same administration of PRIG together
      with the purified protein derivate of tuberculin resulted in 10-fold increase of
      mouse antibody response to PPD. These results demonstrate that PRIG can have some
      immuno-modulating properties concerning low-immunogenic antigens.

PMID- 14577161
TI  - [Activity of key enzymes of heme metabolism and cytochrome P-450 content in the
      rat liver in experimental rhabdomyolysis and hemolytic anemia].
AB  - The 5-aminolevulinate synthase, heme oxygenase, tryptophan-2,3-dioxygenase
      activities, the content of total heme and cytochrome P-450 content in the rat
      liver and absorption spectrum of blood serum in Soret region under glycerol model
      of rhabdomiolisis and hemolytic anemia caused by single phenylhydrazine injection
      have been investigated. The glycerol injection caused a considerable accumulation
      of heme-containing products in the serum and the increase of the total heme
      content, holoenzyme, total activity and heme saturation of tryptophan-2,3
      dioxygenase, as well as the increase of the 5-aminolevulinate synthase and heme
      oxygenase activities in the liver during the first hours of its action and the
      decrease of cytochrome P-450 content in 24 h. Administration of phenylhydrazine
      lead to the increasing of hemolysis products content in blood serum too, although
      it was less expressed. The phenylhydrazine injection caused the increase of
      activities of 5-aminolevulinate synthase, holoenzyme, total activity and heme
      saturation of tryptophan-2,3-dioxygenase, as well as decrease of cytochrome P-450
      content in the rat liver in 2 h. The increase of the total heme content and heme
      oxygenase activity has been observed in 24 h. The effect of heme arrival from the
      blood stream, as well as a direct influence of glycerol and phenylhydrazine on
      the investigated parameters are discussed.

PMID- 14577162
TI  - [Comparison of dyslipoproteinemias in vascular and Alzheimer dementia].

PMID- 14577163
TI  - [Ontogenic characteristics of changes in fatty acid composition of the liver
      lipids as a main substrate for peroxidation in geese].
AB  - Dynamics of fatty acid composition of geese liver lipids in embryogenesis and
      early postnatal period has been investigated. High nonsaturation of these tissues
      lipids is shown during all the period of researches. It is established, that in
      the second half of embryogenesis and in the beginning of postnatal period (first
      two weeks) the increase of oleic acid contents is observed with simultaneous
      decrease of the contents of the polynonsaturated fatty acids (PUFA) showing
      properties of endogenous bioregulators (arachidonic acid (AA), docosahexaenoic
      acid [figure: see text] (DHA). From the two-weeks age of gosling the contents of
      the mentioned acids changes in the opposite direction. The coordination of
      dynamics of TBA-active products with nonsaturation of fatty acids (FA) expressed
      in mEqu/g concerning double bonds, and also with respect to AA/DHA has been
      revealed.

PMID- 14577164
TI  - [Laureates of the Palladin Premium of the National Academy of Science of
      Ukraine].
AB  - The article presents a short information about the Resolution of Ukr.SSR Soviet
      of Ministers on establishing the nominal premium of Presidium the Academy of
      Sciences of Ukr.SSR (of NAS of Ukraine, now) in the field of biochemistry and
      molecular biology dedicated to the famous scientists, founder of the Ukrainian
      biochemical school and the Institute of Biochemistry named after him--academician
      O. V. Palladin. There is a chronologically sequential list presenting all
      Laureates (with photo pictures) awarded by this honourable bonus with displaying
      their scientific works for which they received this reward.

PMID- 14577165
TI  - [Mechanism of antioxidant protection of an organism from oxidative stress].
AB  - The analysis of the literature and authors' data concerning the mechanism of
      antioxidant protection of the organism under conditions of "oxygen stress" is
      submitted. Possible mechanisms of initiation of free radical reactions with
      participation of oxygen and the role of hydroxyl radicals, being one of the basic
      factors, determining toxic action of oxygen, are considered. The methods of
      estimation of antiradical activity of biologically active compounds are
      characterized.

PMID- 14577166
TI  - [Directed immobilization of recognizing elements of biosensor transducers].
AB  - Data about the directed immobilisation of recognising structures on metal and
      silicon surfaces of biosensor transducers are analyzed in the review. Attention
      is paid to such approaches as pretreatment of surface by silanes, thiol compounds
      as well as to formation of polyelectrolyte-based layers.

PMID- 14577167
TI  - [Role of lysine binding sites in activation of plasminogen by streptokinase].
AB  - The function of lysine-binding sites in kringle domains K1-4 and K5 of
      plasminogen (Pg) during its activation by streptokinase (SK) was studied.
      Activation rates of Glu- and Lys-Pg exceed activation rate of mini- and micro-Pg
      26 and 40 times, respectively. 6-Animohexanoic acid (6-AHA) in concentrations
      from 10(-5) to 10(-2) M inhibits activation of Glu-, Lys- and mini-Pg and does
      not impact the activation of micro-Pg. Complete inhibition of Lys-Pg activation
      occurs with presence of 10(-3) M 6-AHA while 90% inhibition of mini-Pg activation
      and 70% inhibition of Glu-Pg activation occur with 10(-2) M 6-AHA. Isolated
      kringles K1-3 and K4 of Pg inhibit activation of Glu-Pg by SK and concentrations
      [I]50 are 4.0 and 8.1 x 10(-6) M, respectively. Catalytic activity of Glu-Pg-SK,
      Lys-Pg-SK and Pm-SK complexes with respect to S 2251 is not inhibited by 6-AHA in
      concentrations from 10(-5) to 10(-2) M. Activation of substrate Pg by Pm-SK
      complex is also inhibited by 6-AHA in concentrations from 10(-5) to 10(-2) M;
      however, this effect of inhibition is significantly weaker than that with
      activation by SK. Cleavage of C-terminal Lys or chemical modification of NH2
      groups of amino acid residues in SK molecule also results in the decrease of the
      Glu-Pg activation rate. Lysin-binding sites in K1-4 and K5 of Pg molecule are
      important at different steps of Pg activation process which includes formation of
      equimolar complex; structural reorganizations resulted in formation of active
      center in Pg; and binding of substrate Pg with Pg-SK complex. Lysin-binding sites
      in K1-4 of Pg are necessary for maintenance of high rate of Pg activation by SK.

PMID- 14577169
TI  - [Interaction of metal cations with Ca2+-transport sites of the plasma membrane
      Ca2+ pump of secretory cells of gastric glands].
AB  - Investigation of Ca2+ transport by calcium pump of the cell plasma membrane of
      the gastric glands isolated from guinea pigs and its inhibition by metal cations
      has been performed. The mainly competitive type of Ca2+ translocation inhibition
      by the calcium pump by metals cations (0.025-1.00 mM) was determined. Potency of
      inhibition increases in such an order (I50, mM): Ba2+ (0.336) < Sr2+ (0.251) <
      Mn2+ (0.099) < Co2+ (0.029) < Cd2+ (0.016). It was shown by one-factor dispersion
      analysis that potency of inhibition depends on ionic radii and hydration enthalpy
      of metal cations and also on stability constants of their complexes with oxygen
      containing bioligands (acetic, aspartic and glutamic acid) (hx2 = 83.73-85.95).
      Dependence of the inhibition constants (I50) on ionic radii is most adequately
      described by the parabolic equation, such a dependence on hydration enthalpy and
      stability constants with oxygen-containing bioligands--by exponential or
      multiplicative equations. The conclusion has been made that selective Ca2+
      translocation by the calcium pump and its inhibition by metal cations is
      determined by the interaction between energy of their interaction with cation
      binding sites of the transport system and energy of hydration. Energetics of such
      interactions depends on the steric factors. The physicochemical model of the Ca2+
      selective translocation by calcium pump and its inhibition by metal cations has
      been proposed.

PMID- 14577168
TI  - [Utilization of purified myometrium cell plasma membrane Ca2+, Mg2+-ATPase for
      comparative estimation of the efficiency of energy-dependent Ca2+-transport
      inhibitors].
AB  - With the aim of comparative estimation of efficacy of well-known inhibitors of
      energy-dependent Ca(2+)-transporting systems their effects were investigated on
      the activity of purified Ca2+, Mg(2+)-ATPase of the myometrium cell plasma
      membranes. From the approved inhibitors (eosin Y, o-vanadate, thapsigargin,
      cyclopiazonic acid, ruthenium red, sodium azide) only eosin Y and o-vanadate are
      potent inhibitors of myometrium sarcolemma Ca(2+)-pump: the values of Ki equal
      0.8 and 4.7 microM, respectively. Thapsigargin and cyclopiazonic acid as well as
      ruthenium red in concentrations inhibiting, respectively, endo(sarco)plasmic
      reticulum Ca(2+)-pump and energy-dependent Ca(2+)-transport in mitochondria had
      no effect on the Ca2+, Mg(2+)-ATPase of the uterus smooth muscle cell plasma
      membrane. Sodium azide (10 mM) blocking completely Ca(2+)-transport in
      mitochondria inhibited activity of the plasma membrane Ca(2+)-transporting ATPase
      by 14%.

PMID- 14577170
TI  - [Changes in hydrodynamic diameter of myometrium plasmalemma vesicles under
      artificial creation of transmembrane proton gradients].
AB  - A method of laser-correlation spectrophotometry was applied for finding the
      effect of proton transmembrane gradient on hydrodynamic diameter of plasmalemma
      smooth muscle vesicles. It is shown, that the building of protons gradient on the
      membrane of vesicles, pHi = 6.0; pHo = 7.5 (delta pH = 1.5) results in the
      reliable decrease of their hydrodynamic diameter (from 212 +/- 6 nm in monitoring
      to 174 +/- +/- 0.25 nm in experiment). The exit of K+ from vesicles (KCl
      concentration inside vesicles is 150 mM), on the contrary, evokes augmentation of
      hydrodynamic diameter. The chemical paravariation of COO-, NH(3+)-groups and
      stabilization of SH-groups of plasmalemma surface results in essential
      modifications in magnitude of the hydrodynamic diameter of vesicles. On the basis
      of experimental data a supposition is expressed about the role of modifications
      of regional position of the functionally important groups of plasmalemma with
      respect to the membrane surface in mechanisms of H+ transport.

PMID- 14577171
TI  - [Effect of ethanol on structural and functional characteristics of rat brain
      cortical membranes in vitro].
AB  - When finding the mechanism of the in vitro ethanol membrane action it was
      established that alcohol in moderate concentrations enhanced the inactivation of
      the rat brain cortex Na+, K(+)-ATPase after modification of the microsomal
      fraction by phospholipase A2 from cobra venom. It is supposed that ethanol
      sensitivity is determined by the structural state of the functional protein-lipid
      enzyme complexes in membrane. The decrease of the intrinsic tryptophan
      fluorescence of the membrane proteins and fluorescence of the probe 1
      anilinonaphthalene-8-sulfonate (both without and under membrane surface charge
      shielding) in the presence of ethanol was revealed. It is concluded, that
      conformational changes of the membrane polar surface area coincide with the
      enzyme inactivation by ethanol.

PMID- 14577172
TI  - [Interaction of oligonucleotides and ATP with preparations of sIgA possessing
      protein kinase activity].
AB  - Interaction of secretory immunoglobulins A of a varying degree of purity with
      oligonucleotides and ATP has been studied by the method of affinity modification.
      For this aim we used reactive derivatives of 32P-labeled deoxyoligonucleotide
      (ClRCH2NHp(T)14) and [gamma-32P]ATP (ClR-32PppA) or ATP (ClR-pppA) bearing a 4
      [(N-2-chloroethyl-N-methyl)amino]benzylamine residue. Preparations of sIgA were
      obtained from human milk by sequential chromatography on protein A-sepharose
      (P1), DEAE-fractogel (P2) and by gel-filtration in 50 mM NaOH (P3). It was
      revealed, that the H- and L-chains of sIgA P1; H-, L-chains and secretory
      component (SC) in sIgA P2 and only SC in sIgA P3 were exposed to modification
      after incubation with ClRCH2NHp(T)14. LPS, DNA, tRNA, heparin, sufficiently
      inhibited the modification of chains of sIgA P1. These competitors did not
      influence the modification of H- and L-chains of sIgA P2, but DNA, tRNA, heparin,
      inhibited binding of SC with the modifier. Suppressing affect of binding of
      ClRCH2NHp(T)14 with secretory component of sIgA P3 by d(T)14 has been observed as
      well. The research of ClR-32PppA interaction with sIgA P3 has shown that H- and L
      chains of sIgA are exposed to modification. ATP inhibited the reaction. Study of
      the influence of modification on the protein kinase activity of sIgA P3 has
      revealed, that the preliminary incubation of sIgA P3 with ClR-pppA leads to
      inhibition of protein kinase activity. We suggest that sIgA, possessing the
      protein kinase activity (sIgA-abzymes) has an ATP-binding center (catalytic
      center) and has an oligonucleotide-binding center as well.

PMID- 14577174
TI  - [Interaction of annexin VI with actin].
AB  - Actin polymerization was investigated using fluorescence probe N-(1
      pyrenyl)iodoacetamide, which was bound covalently to reactive sulfhydryl group,
      Cys-373. Labeled actin in the bulk was 0.5 to 1% of total actin concentration.
      Actin polymerization at concentration 12 mM was started by addition of 20 mM KCl
      and 2 mM MgCl2. The label fluorescence was excited at 365 nm and registered at
      386 nm. Under actin polymerization the label fluorescence increased almost 10
      times. Two main phases may be distinguished in the process of actin
      polymerization: 1) monomer activation and nucleus (trimer) formation, 2) growth
      of actin filaments on the nuclei. In our experimental conditions, both for pure
      actin and for that with added annexin VI, the 1st phase continued for about 3 min
      and after that the 2nd phase was perfectly approximated by exponential
      dependence. An analysis of the exponential curves showed that actin monomer
      lifetime increased from 327 s, at annexin absence, to about 373 s at 0.7 microM
      annexin and more. Calculation of rate constants at two ends of growing actin
      filament suggests that annexin VI binds with pointed ("slow") end so that at
      sufficient annexin concentration the filament grows only on barbed ("fast") end.
      Our results, together with data of other researchers showing that annexin VI
      binds with the inner membrane surface of smooth muscle cell through Ca2+, may
      indicate that, at Ca2+ entering the cell, this annexin binds actin filament
      pointed ends to cell surface making it ready for the act of contraction.

PMID- 14577173
TI  - [Antihypoxic effect of vitamin E and its derivative in rats under modeling of
      hypoxic conditions of different origin].
AB  - The increase of ubiquinone content in myocardial mitochondria and
      succinateubiquinone reductase activity in rat blood leucocytes under hypoxic
      hypoxia and acute microfocal myocardial damage [table: see text] have been shown.
      At the same time the succinateubiquinone reductase activity of rat myocardial
      mitochondria do not change substantially. We simultaneously observe the dramatic
      drop in NADH-ubiquinone reductase activity under experimental myocarditis. This
      fact demonstrates higher stability of succinateubiquinone reductase system and
      differences in metabolical processes under hypoxic conditions of different
      origin. All vitamin E derivatives studied demonstrate substantial antihypoxic
      activity, which is connected with increased animals' survivability, ubiquinone
      content in myocardial mitochondria and stabilization and leveling of
      succinateubiquinone reducatse activity in rat blood leucocytes. alpha
      Tocopherolacetate with shortened to six carbon atoms side chain is the most
      effective in this respect. We discuss possible mechanisms for the realization of
      vitamin E and its active derivative's antihypoxic effect.

PMID- 14577175
TI  - [Effect of glutaminic acid on the activity of the sympatho-adrenal system and the
      concentration of calcium in urine under conditions of development of the alcohol
      abstinence syndrome].
AB  - The paper deals with the influence of glutaminic acid on the functional activity
      of the sympatho-adrenal system and the concentration of calcium in urine under
      conditions of the alcoholic abstinence syndrome development. Changes in the
      functional activity of sympatho-adrenal system and in the concentration of
      calcium in the process of the abstinence syndrome development are shown to be of
      the phase character. It is established that in the period of the developed
      abstinence syndrome glutaminic acid produces a normalizing action on the
      excretion of adrenaline and dopamine and also facilitates a decrease in the level
      of calcium in urine.

PMID- 14577176
TI  - [State of GABA-benzodiazepine receptor complex in diabetic neuropathy: effect of
      nicotinamide and nicotinoyl-GABA].
AB  - An increase in GABA uptake by isolated rat brain synaptic endings as well as a
      decrease of pharmacologically active GABA analogue muscimol specific binding have
      indicated a physiologically drastic failure in realization of GABA-mediated
      inhibitory effects in CNS induced by diabetic encephalopathy. In spite of the
      impairment of inhibitory function of GABAergic transmission in diabetes a crucial
      activation of benzodiazepine receptors was determined, as it is tested by the
      increase in specific binding of flunitrazepam by synaptic membranes. This
      increase may play an important role in endogenous control of neural activity
      associated with the factors undefined so far. Using the approach that GABA, and
      several synthetic GABA agonists, appear to increase the affinity of the
      benzodiazepine recognition sites for such ligands, presumably by some allosteric
      mechanism, the findings concerning the in vitro binding assay technique confirm
      at least some of the functional characteristics observed between GABA and
      benzodiazepine receptors in vivo under pathological conditions. Indeed, the
      absence of activating effect on the affinity of flunitrazepam specific binding in
      the presence of micromolar concentrations of exogenous GABA implicate diabetes
      induced alterations in coupling GABA- and benzodiazepine receptors that might be
      linked to changes in conformantial state of this membrane-bound complex and could
      partially explain diabetes-induced impairments of GABAergic transmission
      evaluated in the present study. Our study suggests that nicotinamide and
      especially GABA play an important role in improving the functioning of brain GABA
      benzodiazepine complex impaired in diabetes through specific ligand-mediated
      mechanism and can be useful in the management of diabetes-associated brain
      failures.

PMID- 14577177
TI  - [Obtaining bioluminescent bacterial strains for detection of thallium ions].
AB  - The possibility of Alcaligenes eutrophus T1 luxphenotype creation by temperature
      induced mutagenesis has been shown. These mutants are able to emit light after
      induction by thallium ions. This biological method of thallium detection
      possesses high specificity and sensitivity (0.5 microM of metal). Such microbial
      cells can be used to quantify bioavailability of thallium part in the
      environment.

PMID- 14577178
TI  - [Effect of surface-active substances on bioluminescence intensity of bacteria].
AB  - The study of sensitivity of luminous bacteria isolated from the Black and Azov
      seas to surfactants from various classes was carried out. It was shown that
      cationic surfactants had a strong inhibition effect on bacterial luminescence in
      contrast to anionic and in particular nonionic surfactants. To increase the
      luminous bacteria sensitivity to the action of OP-10 (nonionic surfactant) and
      ABS (anionic surfactant), which are widely used in industry, several approaches
      have been developed. They include modulation of bacterial sensitivity by the
      additives of cationic substances, use of luminous bacteria at a logarithmic stage
      of growth, realization of biotesting at low pH = 5.5. The use of these approaches
      allows to lower effective concentrations of OP-10 and ABS, which caused a
      decrease of bioluminescence by 50%, 3-200 times and opens perspectives for the
      use of the bioluminescent method to study these surfactants toxicity on the
      principle of biosensorics.

PMID- 14577179
TI  - [Activity of 5-aminolevulinate synthase in rat liver during degradation of
      cytochrome P-450 caused by administration of cadmium chloride].
AB  - The 5-aminolevulinate synthase, tryptophan-2,3-dioxygenase activities and
      cytochrome P-450 content in the rat liver was studied in different terms after
      CdCl2 administration and after administration of metal salt against a background
      of 2-hours action of alpha-tocopherol. The lowering of activity of 5
      aminolevulinate synthase in 2 h with the consequent increase of the enzyme
      activity in 6 h and 24 h was detected. The holoenzyme activity and heme
      saturation of tryptophan-2,3-dioxygenase increased 6 h after CdCl2
      administration. The holoenzyme activity and the total activity of tryptophan-2,3
      dioxygenase rised in 24 h. The level of cytochrome P-450 lowered. Preliminary
      administration of alpha-tocopherol prevented changes of studied parameters 24 h
      after CdCl2 administration. The relationship between decrease of cytochrome P-450
      level and 5-aminolevulinate synthase activation are discussed.

PMID- 14577180
TI  - [Effect of TMV-infection on protein and carbohydrate content in hypersensitive
      tobacco plants and their antiviral and hemagglutinating activity].
AB  - Changes in content of proteins and carbohydrates of sensitive and supersensitive
      tobacco and datura plants and their antiviral and hemagglutinating activity under
      tobacco mosaic virus infection were investigated. It was shown that the content
      of these substances was increased on early stages of virus infection in
      hypersensitive plants. Antiviral and hemagglutinating activity of the obtained
      substances was shown.

PMID- 14577181
TI  - [Activity of purine enzyme metabolism in rat thymocytes after irradiation and
      after administration of riboxine].
AB  - It has been established, that the total X-ray irradiation of animals takes
      influence upon the functional activity of key enzymes of adenine nucleotides
      metabolism: adenylatekinase, AMP deaminase, 5'-nucleotidase, adenosine deaminase
      and purine nucleoside phosphorylase in rat's thymocytes. The increase of activity
      of the investigated enzymes is observed in our experiment, except 5'
      nucleotidase, which activity is authentically decreasing after irradiation (1.0
      and 7.78 Gy). The injection of the preparation riboxine to experimental animals
      15 min prior to the exposure has normalized the purine exchange enzymes activity.

PMID- 14577182
TI  - The problem of prozone in serum antibody titration and its mathematical
      interpretation.
AB  - The question of the mechanism of "prozone" creation was considered from the point
      of view of the concentrations of free and semi-blocked bivalent antibodies in the
      mixture of these antibodies with monovalent antigen. Using the so called
      "coordinates of dilution", suggested by the author earlier, it was possible to
      calculate the relationships between the concentrations of either free or semi
      blocked bivalent antibodies and the dilution of the antigen-antibody mixture. It
      was shown that dilution of antigen-antibody mixture leads to an increase of the
      concentration of free bivalent antibodies and simultaneous sharp decrease of the
      concentration of semi-blocked antibodies. It is suggested, that such a
      relationship is quite enough for the creation of prozone effect in reactions,
      when only bivalent antibodies are active and semi-blocked antibodies compete with
      free antibodies, providing inhibition of the reaction.

PMID- 14577184
TI  - Gold Medal Award for Life Achievement in the Practice of Psychology. Nicholas A.
      Cummings.

PMID- 14577183
TI  - Gold Medal Award for Life Achievement in the Application of Psychology. Charles
      D. Spielberger.

PMID- 14577185
TI  - Gold Medal Award for Life Achievement in Psychology in the Public Interest. Ethel
      Tobach.

PMID- 14577186
TI  - Gold Medal Award for Life Achievement in the Science of Psychology. Robert
      Rosenthal.

PMID- 14577187
TI  - Award for Distinguished Teaching of Psychology. Victor A. Benassi.

PMID- 14577188
TI  - Psychology and health. Research, practice, and policy.
AB  - Since World War II, American psychology's role in health care has significantly
      expanded. This was formally recognized in 2001 when the membership of the
      American Psychological Association (APA) approved a bylaw change in its mission
      statement to include the word health. An accumulating body of research
      demonstrates and recent reviews conclude that psychological factors are primary
      in health and in illnesses. This article proposes a vision of psychology that
      endorses a bio-psycho-socio-cultural model of health research and interventions.
      The author provides 4 definitions of health, reviews selected psychology health
      research and interventions, summarizes APA's recent health-related activities,
      and presents 5 policy recommendations for consideration and debate.

PMID- 14577189
TI  - Rethinking education in psychology and psychology in education. The inaugural
      Education Leadership Conference.
AB  - The inaugural Education Leadership Conference was convened by the American
      Psychological Association (APA) in October 2001 to provide a forum for groups and
      organizations across all levels of education and training to address issues of
      mutual concern, to promote a shared disciplinary identity among education and
      training leaders in psychology, and to influence public policy regarding
      education in psychology and psychology in education. Participants from 23
      national education and training organizations, 25 APA divisions, and national
      credentialing organizations in psychology identified 8 major issues for education
      and training in psychology and addressed a number of specific questions relevant
      to ongoing work of the Board of Educational Affairs.

PMID- 14577190
TI  - [Phenotypic characteristics of coagulase-negative Staphylococci colonizing
      pleural drains in patients with lung cancer after thoracic surgery].
AB  - Coagulase-negative staphylococci (CNS) represent an important group of etiologic
      agents of infections associated with plastic biomaterials, e.g. drains. In the
      present paper 33 strains of CNS were characterized. All of them were isolated
      from fluid of pleural drains in patients with lung cancer after pulmonary
      resection under conditions of antimicrobial prophylaxis. The most frequently
      isolated species were Staphylococcus epidermidis and S. warneri. The majority of
      CNS strains showed ability to produce slime and possessed hydrophobic properties
      of cell surface. Strains of CNS resistant to penicillin and oxacillin, but
      sensitive to amoxicillin/clavulanate were isolated most frequently. Only two
      methicillin-resistant strains, belonging to S. haemolyticus, were found. The
      obtained data indicate that CNS strains colonizing pleural drains had potential
      ability to adhere to smooth surfaces. Most of isolated strains were susceptible
      to antibiotics and chemotherapeutics routinely used in staphylococcal infections.

PMID- 14577192
TI  - [Application of released proteins (RPs) of Yersinia Enterocolitica for
      serological diagnosis of yersiniosis. I. Antigen for ELISA].
AB  - The usefulness of the released proteins (RPs) prepared in our laboratory from the
      strain Y. enterocolitica for the serological diagnosis of yersiniosis was
      estimated. Yersinia enterocolitica 0:8 was cultured under calcium deficient
      conditions and the virulence factors were isolated from the culture supernatant.
      The purified proteins were solubilized using sodium dodecyl sulfate. The results
      of ELISA using released proteins obtained in our laboratory as the antigen were
      compared to the results of commercial ELISA-Mikrogen and ELISA-Euroimmun. One
      hundred serum samples obtained from patients suspected in clinical investigations
      for jersiniosis were tested. Comparison of the frequency of detecting in
      particular ELISA antibodies to Yersinia showed a high (> 85%) agreement of the
      results in all of the immunoglobulin classes. The highest sensitivity (97.4%) and
      specificity (95.4%) was displayed by the ELISA with our antigen in relation to
      the ELISA-Mikrogen when determining antibodies of IgM class.

PMID- 14577191
TI  - [Application of PCR-fingerprinting reactions for typing group B Streptococci
      using ERIC-1 and ERIC-2].
AB  - Usefulness of PCR--fingerprinting technic using ERIC 1 and ERIC 2 primers for
      epidemiologic analysis of Group B Streptococci was assessed. 120 strains isolated
      from various clinical samples were tested. Amplification reactions were carried
      out in automatic termocycler Poly Gen using two primers ERIC 1 and ERIC 2.
      Products of the amplification were subjected to horizontal electrophoresis in
      1.5% agarose gel. Using primer ERIC 1 six DNA patterns were found. Patterns B and
      C were the most often encountered, containing 34.2% and 35.0% of strains. Less
      often pattern D occurred including 12.5% of strains. In case of primer ERIC 2
      lower differentiation has been achieved, because only four DNA patterns has been
      found, three of them occurred with similar frequency 29.2% to 33.3%. Taking into
      consideration the patterns gained by means of two primers thirteen genotypes have
      been identified. Dominated two patterns CD and BC, comprising 30.0% and 24.1%
      Group B Streptococci. More rarely DA and BA occurred (10.8% and 8.3%). Remaining
      patterns make 0.8% to 6.7% strains. Among reference Group B Streptococci strains
      belonging to nine serologic types using two primers various genetic patterns were
      obtained.

PMID- 14577193
TI  - [Occurrence and characteristic of P-like adhesin among Klebsiella strains].
AB  - Colonisation and remaining of microorganism on mucus membrane of microorganism is
      tightly connected with adhesion mechanisms and determine the first step of
      physiological settlement of the organism or the first stage of clinically
      demonstrated infection. In Klebsiella rods there are known three types of
      fimbrial adhesins (type 1, 3 and KPF-28) and non-fimbrial adhesin CF29K. It is
      stated that Klebsiella strains adhesions are responsible for their adherence to
      the epithelial cells of both respiratory and urinary tracts and to intestine
      epithelium. The in vitro research affirmed Klebsiella rods adherence to protein
      matrix. The aim of our work was the establishment of character, receptor
      specificity and the appearance frequency of P-like called adhesin. The frequency
      of expression of P-like adhesin was estimated among 380 isolated from the
      patients strains on the basis of agglutinating methods. The amorphic character of
      P-like adhesin was proved using electron microscopy method. The isolation and
      purification of P-like protein with a help of affinity chromatography enabled to
      estimate the receptor specificity of the adhesin. The receptor specificity was
      established as similar to E.coli PapG adhesin.

PMID- 14577194
TI  - [Evaluation of the usefulness of multitemperature single-stranded conformational
      polymorphism (MSSCP) for differentiation of selected bacterial gene variants
      (alleles)].
AB  - Recently, the single strand conformation polymorphism (SSCP) analyses were shown
      to be useful for identification a variety of bacterial genes. Although, SSCP was
      successfully applied for detection of single nucleotide polymorphism (SNP), it
      was also considered a time consuming and insufficiently reliable technique.
      Therefore, the modified Multitemperature-SSCP method was introduced. It was shown
      to be reliable and time effective technique due to a stringent control of the gel
      temperature and utilization of a high voltage up to 1 kV. In this study the
      usefulness of MSSCP for differentiation of gene variants and detection of the
      single point mutations was evaluated, using Yersinia enterocolitica O3 and O8 ail
      alleles or genes blaCTX-M-15 and blaCTX-M-3, which differs by a single point
      mutation. The 425 and 251 bp fragments of O3 and O8 ail alleles containing 15 and
      11 point mutations respectively, as well as 277 and 208 bp fragments of both
      blaCTX-M genes differing in positions 243 and 62 were PCR amplified, denatured
      and loaded onto 7% and 9% polyacrylamide nondenaturing gel. Electrophoresis was
      carried out in the DNA-Pointer apparatus (Kuchrczyk, Poland) at voltage ranging
      from 500 to 750 V. The thermal profile consisted of 50 min. at 35 degrees C, 40
      min at 20 degrees C and 40 min at 5 degrees C. Obtained results showed, MSSCP was
      capable to differentiate ail alleles independently of the length of analyzed
      fragment. However, the 425 bp fragment profile consisted of three bands, whereas
      251 bp revealed two bands. The single point mutation in blaCTM, genes was also
      successfully distinguished by MSSCP in both tested fragments. Surprisingly, 277
      bp fragment profile showed differences more apparently than 208 bp. Summarizing,
      MSSCP was found to be useful, sensitive and time efficient tool for detection of
      multiple and single point mutations in DNA fragments ranging from 208-425 bp.

PMID- 14577195
TI  - [Cytotoxicity of DMSO for MRC5, Chang liver and CV1 cells evaluated in vitro by
      LK, MTT and NR assays].
AB  - Evaluation of chemicals cytotoxicity plays fundamental role in many in vitro
      investigations. The way of assessment of cytotoxicity depend on aim of study,
      characteristic of used cells and mode of action of investigated chemicals. The
      principal aspect of these investigations is validation of used method. In this
      paper validation of three different cytotoxicity assays is presented: total cell
      number measurement (LK), microplate assay measured mitochondrial dehydrogenase
      activity (MTT) and colorimetric assay measured ability of live cell to uptake
      neutral red (NR). The investigation was performed on different cells (MRC5, CV1 i
      Chang Liver) with DMSO as reference agent.

PMID- 14577196
TI  - [Fluoroquinolone susceptibility of Pseudomonas aeruginosa strains isolated from
      clinical materials].
AB  - The goal of our research was an analysis of sensitivity of Pseudomonas aeruginosa
      to fluoroquinolones (SPX, PEF, UB, LOM, CIP, ENX, OFX, NOR). The sensitivity was
      tested by disk diffusion method, according to NCCLS standards. 120 strains
      isolated from hospitalized (76 strains) and outpatient clinic (44 strains)
      persons were tested. The highest sensitivity of strains was observed to
      norfloxacin (36.8% and 86.4% of strains, respectively) and ciprofloxacin (30.3%
      and 81.8%). None of tested microorganisms was sensitive to flumequine. Resistant
      strains, isolated from sick persons in outpatient clinics were fewer (13.6%) as
      compared to hospitalized persons (51.3%).

PMID- 14577198
TI  - [The extent of immune response impairment vs. the prevalence and clinical form of
      oral candidiasis in HIV patients].
AB  - The objective of the study was a mycological and clinical evaluation of the
      course of oral cavity fungal infection in HIV patients in relation to the immune
      response impairment. The patients were examined physically (symptoms and signs)
      and mycologically (isolation and identification of fungi, semiquantitative
      evaluation their growth abundance in the cultures); the immunity status was
      expressed in terms of the number of CD4 lymphocytes. The most frequently isolated
      fungal species was Candida albicans. The decreasing immunity was conductive to
      more abundant fungal growth in the oral cavity as well as to more frequent
      occurrence of clinical manifestations of candidiasis.

PMID- 14577197
TI  - [Anaerobic bacteria in bronchoalveolar lavage fluid (BAL) after thoracic
      surgery].
AB  - Purpose of this study was to find out what kind of anaerobic bacteria were in
      lower respiratory tract and how often they were present there considering
      patients after thoracic surgery. Also, what is susceptibility of bacteria to
      antibiotics. Research covered 30 patients after operation. Material for research
      was bronchoalveolar lavage (BAL) taken during bronchoscopy. Collected sample was
      cultivated in anaerobic and aerobic conditions. Anaerobic bacteria were found in
      28 samples (93%). Totally there were 100 anaerobic bacteria strains. The most
      common Gram-negative rods were from genus Prevotella (24 strains, 24%) and
      Bacteroides (15 strains, 15%). Gram-negative bacteria except Bacteroides
      characterised biggest susceptibility to imipenem, piperacillin/tazobactam,
      amoxicillin/clavulanate, ampicillin/sulbactam, piperacillin, clindamycin and
      metronidazol. Bacteroides were susceptible to imipenem, piperacillin/tazobactam
      and metronidazol. Among Gram-positive anaerobic bacteria mostly were isolated
      from cocci Peptostreptococcus (18 strains, 18%) and were susceptible to all
      antibiotics. Gram-positive rods were in most cases represented by Actinomyces (12
      strains 12%) and were highly susceptible to all antibacterial means except
      metronidazol (100% is resistant).

PMID- 14577199
TI  - [The presence of bacteria and yeast like fungi in specimens from surgical
      patients].
AB  - The aim of this study was to determine the incidence of Candida spp. strains in
      specimens obtained from surgically treated patients as well as to analyze the
      accompanying bacterial flora, both aerobic and anaerobic. The material came from
      two groups of patients. In the first group consisting of patients operated for
      colon and rectum carcinoma, the samples included peritoneal fluid, colon or
      rectum bioptates, pus, blood, and wound swabs. In the other group, biopsy
      material and smears from post operation wounds were taken from patients who
      underwent a surgical treatment of larynx carcinoma. Altogether, 282 various
      clinical specimens from 165 patients were analysed, and 41 Candida spp. strains
      were isolated: 39 strains of C. albicans and 2 strains of C. tropicalis. In 20
      out of 41 specimens infected with Candida spp. (48.8%) the co-infection with
      bacterial aerobic flora was found. In 10 cases (24.4%), the fungi were isolated
      together with aerobic and anaerobic bacterial flora, whereas in 2 specimens
      (4.9%) the anaerobes and Candida albicans were diagnosed. The remaining 9 samples
      showed only the presence of Candida spp. (21.9%). From among aerobic bacterial
      flora Enterococcus spp. strains (n = 17) and Gram negative rods from
      Enterobacteriaceae family (n = 13) were the most frequently isolated. The
      bacterial strains of Streptococcus spp. (n = 5), Pseudomonas spp. (n = 3),
      Staphylococcus spp. and Corynebacterium spp. (2 strains, both) were identified
      more rarely. Bacteroides spp. were the most frequent members of bacterial
      anaerobic flora (n = 10). Other isolated anaerobic bacteria were classified as
      Fusobacterium spp. or Peptostreptococcus spp. (1 strain each). E. coli and
      Enterococcus spp. strains of aerobic bacterial flora were more frequently
      isolated together with Candida spp. CONCLUSIONS: (i) Mixed bacterial flora was
      found to predominate in the clinical material from the patients after surgery.
      (ii) Candida spp. were most frequently found together with aerobic bacterial
      flora.

PMID- 14577200
TI  - [Quality control in pathological anatomy: 10 years' experience].
AB  - The quality assurance scheme in use at the Section of Anatomic Pathology of the
      University of Bologna-Bellaria Hospital is described. Since 1992 a quality
      assurance (QA) scheme has been set up in this Institution. The scheme and results
      have been reported in this same Journal previously 1-3: here are reported the
      changes to the scheme that have intervened in the last four years. All data
      collected from January 1999 to December 2002 have been reviewed for monitoring
      the laboratory performance. Emphasis has been given to changes that have been
      introduced recently to improve QA.

PMID- 14577201
TI  - [Thin-layer cytology in endometrial diagnosis].
AB  - Our purpose was to test the liquid-based thin layer method on the endometrial
      cytology. One hundred sixty two consecutive patients before the hysterectomy (55
      women because of various causes; 107 asymptomatic postmenopausal women because of
      prolapsed uterus) had the endometrial cytology (all women) and the biopsy (107
      postmenopausal women prolapsed uterus affected). Cytohistologic concordance was
      98%: all endometrial neoplasms and atypical hyperplasia (10 cases) and 15 of the
      18 (83%) simple hyperplasias were diagnosed by thin layer endometrial cytology.
      In asymptomatic postmenopausal women cytology gave sufficient material for the
      diagnosis significantively more often than endometrial biopsy (respectively 82%
      and 24%; p = 0.000).

PMID- 14577202
TI  - [Expression of the cdx2 gene in benign intestinal-type mucinous ovarian tumors].
AB  - INTRODUCTION: Cdx2 gene belongs to the homeobox caudal gene family and it is
      located, in humans, on the 13q12.3 chromosome; in particular it codifies for a
      specific nuclear transcription factor which induces intestinal epithelium
      development, differentiation and preservation. Cdx2 expression in the human
      embryo can be observed in the intestinal epithelium starting from the sixth week
      of gestation. In the foetus and in adults it is observed in the whole enteric
      tube from the duodenum to the anal canal. Because of its organ specificity, cdx2
      is an important marker for metastatic neoplastic lesions. Cdx2 is expressed in
      intestinal metaplasia and it is focally positive in adenocarcinomas of intestinal
      type of the stomach, pancreas and gall bladder as well as in ovarian mucinous
      adenocarcinomas. FINALITY OF THE STUDY: The aim of our study is to detect cdx2
      positivity, with evaluation of its characteristics and expression, in ovarian
      mucinous cistoadenomas. MATERIALS AND METHODS: We examined cdx2 expression in 50
      ovarian mucinous cistoadenomas (mean age between 17 and 85), 19 of which were
      localised in the right ovary while 31 in the left one. Standard staining
      techniques (H&E), histochemistry (AB-PAS) ed immunohistochemistry with monoclonal
      antibodies against cdx2 (Biogenex/Menarini cdx2-88, batch MU3920402XS) were
      performed on formalin fixed and paraffin embedded material. For each case two
      samples were analysed. RESULTS: Morphological evaluation of the 50 benign
      mucinous tumours distinguished 47 of endocervical type and 3 of intestinal type.
      These data were also confirmed by characterisation of mucin profile by AB-PAS
      staining. Using anti-cdx2 antibodies tumours of endocervical type were negative,
      while 3 intestinal type tumours were positive. In particular 2 cases presented
      diffuse nuclear positivity, while in one positivity was only focal. DISCUSSION:
      Until today only two studies deal with cdx2 expression in mucinous ovarian
      tumours: 5 and 14 cases strong respectively. In the former, cdx2 expression was
      positive in all cases (100% positivity--5/5), in the latter cdx2 expression was
      positive in 64% of cases (9/14). In order to explain the lack of consistency in
      these data one must analyse ovarian mucinous tumours in detail. These neoplasms
      are divided into two subtypes: endocervical type and intestinal type. Distinction
      between these two types is near to impossible in malignant tumours, difficult in
      borderline tumours while it becomes easy in benign ones. Among benign tumours,
      endocervical type tumours are the majority, while intestinal type are much more
      infrequent. Our 50 case strong casistic is sufficiently ample to include 3 cases
      of intestinal type, all of which are cdx2 positive, compared to a complete
      negativity in the remaining 47 tumours clearly of endocervical type. We believe
      that the lack of consistency between the aforementioned studies is probably due
      to the fact that neither work contemplates the subdivision in intestinal and
      endocervical types. It is hence possible to hypothesise a selective and specific
      correlation between cdx2 positivity and the intestinal type epithelial component
      of ovarian tumours.

PMID- 14577203
TI  - [Solitary ganglioneuroma of the ileo-cecal valve].
AB  - Ganglioneuromas may occur in the small and large intestine as either solitary
      lesions or, more commonly, as multiple lesions (ganglioneuromatosis). The former
      are very rare, whereas ganglioneuromatosis may be associated with von
      Recklinghausen's disease and multiple endocrine neoplasia (MEN) type II B. We
      described the clinicopathologic features of a case of solitary polypoid
      ganglioneuroma of the ileocecal valve. The lesion was endoscopically diagnosed in
      a 27 year old man, with a history of abdominal pain. No association with von
      Reckling-hausen's disease or MEN was identified. Mutational analysis for RET was
      negative. Microscopically, the tumor consisted of a proliferation of well
      differentiated Schwann cells and ganglion cells in the lamina propria. The
      solitary polipoid ganglioneuroma is invariably benign. It shows no evidence of
      recurrence after total excision.

PMID- 14577204
TI  - [Cutaneous angiosarcoma arising after radiotherapy treatment of a breast
      carcinoma. Description of a case and review of the literature].
AB  - Cutaneous angiosarcomas occurring as a complication of radiation therapy for
      breast cancer are rare. To the best of our knowledge 37 cases have been reported
      in English literature during the last two decades. We describe a case of
      angiosarcoma arising in the skin of a breast previously irradiated for breast
      carcinoma. The patient, a 74-year-old woman, had been treated with conservative
      surgery and radiotherapy for a pT1N0 infiltrating ductal carcinoma of the left
      breast in 1993. Nine years later a skin lesion, which was interpreted as a
      recurrence, arose in the same site. A biopsy obtained from the lesion, and
      initially considered to be negative for cancer, showed istological features
      consistent with those of the atypical vascular lesion. Seven months later the
      same lesion transformed in a 5 x 3 reddish mass which at histological examination
      was diagnosed as an high grad post-irradiation angiosarcoma of the skin of the
      breast. Data on previously reported post iradiation angiosarcoma of the breast
      are reviewed; further consideration on differential diagnosis between those
      lesions and atypical vascular lesions are presented.

PMID- 14577205
TI  - [Enterocolic phlebitis. Description of a case and review of the literature].
AB  - OBJECTIVE: To report about a case of enterocolic phlebitis, a rare cause of
      ischemic intestinal necrosis. RESULTS AND CONCLUSIONS: The patient, a 71 year-old
      male, presented with signs of acute abdomen. A right hemicolectomy was performed,
      which revealed a tubulovillous adenoma with high grade dysplasia located in the
      ascending colon, and a diffuse ischemic colitis. A localized lymphocytic and
      granulomatous phlebitis was present in the resected colon. The arteries were
      spared by the inflammatory process. The patient is alive and well 7 years after
      surgery. The literature concerning enterocolic phlebitis, a peculiar form of
      localized intestinal vasculitis, is briefly summarized.

PMID- 14577206
TI  - [Poorly differentiated breast carcinoma with an abundant myoepithelial component:
      morphologic and immunohistochemical features and mammaglobin gene expression ].
AB  - In this report, we describe a case of poorly differentiate myoepithelial cell
      rich carcinoma in with morphological findings of large poligonal nests with
      festoon-like pattern sometimes showing central necrosis, reminiscent of a comedo
      like pattern and numerous mitoses. Immunohistochemical staining shows positive
      reaction for cytokeratin AE/1, CAM 5.2, 34 beta E12, vimentin, smooth muscle
      actin, EMA, S100 protein and oncogene cERB.b2 and negative for estrogen,
      progesterone, GFAP and chromogranin. Moreover, this carcinoma show the expression
      of the mammaglobin mRNA, a highly specific marker of breast epithelial cells that
      it is not expressed in all breast carcinoma.

PMID- 14577207
TI  - [Mixed neoplasia of the stomach: description of a case of tubular adenoma
      combined with carcinoid].
AB  - We report about a gastric polyp that was a combination of tubular adenoma and
      carcinoid. The patient, a 76 year-old male, presented with 1 cm sessile polyp,
      located in the gastric body, that was a combination of a tubular adenoma with
      moderate dysplasia and a small carcinoid. Immunohistochemically, the latter
      component was positive for chromogranin and synaptophysin. The patient is alive
      and well 10 months after endoscopical polypectomy.

PMID- 14577208
TI  - The role of methods in the discovery of the cytochromes P450.

PMID- 14577209
TI  - Cytochrome P450 nomenclature.

PMID- 14577210
TI  - Spectral analyses of cytochromes P450.

PMID- 14577211
TI  - Purification of cytochromes P450. Rat and human hepatic forms.

PMID- 14577212
TI  - Isolation and purification of constitutive forms of microsomal cytochrome P450.

PMID- 14577213
TI  - Purification of extrahepatic cytochromes P450.

PMID- 14577214
TI  - Purification of cytochromes P450: products of bacterial recombinant expression
      systems.

PMID- 14577215
TI  - Cytochrome P450 reconstitution systems.

PMID- 14577216
TI  - Catalytic assays for human cytochrome P450.

PMID- 14577217
TI  - Enzymatic analysis of cDNA-expressed human CYP1A1, CYP1A2, and CYP1B1 with 7
      ethoxyresorufin as substrate.

PMID- 14577218
TI  - Spectrofluorometric analysis of CYP2A6-catalyzed coumarin 7-hydroxylation.

PMID- 14577219
TI  - Determination of the CYP2B6 component of 7-ethoxy-4-trifluoromethylcoumarin O
      deethylation activity in human liver microsomes.

PMID- 14577220
TI  - High-performance liquid chromatographic analysis of CYP2C8-catalyzed paclitaxel 6
      alpha-hydroxylation.

PMID- 14577221
TI  - Determination of CYP2C9-catalyzed diclofenac 4'-hydroxylation by high-performance
      liquid chromatography.

PMID- 14577222
TI  - CYP2C19-mediated (S)-mephenytoin 4'-hydroxylation assayed by high-performance
      liquid chromatography with radiometric detection.

PMID- 14577223
TI  - CYP2D6-dependent bufuralol 1'-hydroxylation assayed by reversed-phase ion-pair
      high-performance liquid chromatography with fluorescence detection.

PMID- 14577225
TI  - Thin-layer chromatographic analysis of human CYP3A-catalyzed testosterone 6 beta
      hydroxylation.

PMID- 14577224
TI  - Spectrophotometric analysis of human CYP2E1-catalyzed p-nitrophenol
      hydroxylation.

PMID- 14577226
TI  - Determination of CYP4A11-catalyzed lauric acid 12-hydroxylation by high
      performance liquid chromatography with radiometric detection.

PMID- 14577227
TI  - An isocratic high-performance liquid chromatographic assay for CYP7A1-catalyzed
      cholesterol 7 alpha-hydroxylation.

PMID- 14577228
TI  - Use of 7-ethoxycoumarin to monitor multiple enzymes in the human CYP1, CYP2, and
      CYP3 families.

PMID- 14577229
TI  - Expression of eukaryotic cytochromes P450 in E. coli.

PMID- 14577230
TI  - Expression of mammalian cytochromes P450 in yeast.

PMID- 14577231
TI  - Expression of cytochromes P450 in a baculovirus system.

PMID- 14577232
TI  - Expression of cytochromes P450 in mammalian cells.

PMID- 14577233
TI  - Monoclonal antibodies to cytochromes P450.

PMID- 14577234
TI  - Targeting antipeptide antibodies towards cytochrome P450 enzymes.

PMID- 14577235
TI  - Signals for retention of cytochrome P450 in the endoplasmic reticulum.

PMID- 14577236
TI  - Quantification of cytochrome P450 gene expression by RNase protection analysis.

PMID- 14577237
TI  - Hepatocyte cultures in drug metabolism and toxicological research and testing.

PMID- 14577238
TI  - Isolation of rat hepatocytes.

PMID- 14577239
TI  - Collagen-gel cultures of rat hepatocytes: collagen-gel sandwich and
      immobilization cultures.

PMID- 14577240
TI  - Rat hepatocyte cultures. Conventional monolayer cultures and cocultures with rat
      liver epithelial cells.

PMID- 14577241
TI  - Isolation of periportal and pericentral hepatocytes.

PMID- 14577242
TI  - Perifusion culture of hepatocytes.

PMID- 14577244
TI  - Reconstruction of human epidermis in vitro.

PMID- 14577243
TI  - Human hepatocyte culture.

PMID- 14577245
TI  - Gene transfer and expression.

PMID- 14577246
TI  - Lipid-mediated gene transfer into normal adult human hepatocytes in primary
      culture.

PMID- 14577247
TI  - Identification of regulatory protein-binding sites in cytochrome P450 genes by
      means of the gel-retardation assay.

PMID- 14577248
TI  - Cytochrome P450 gene regulation. Analysis of protein-DNA interactions in situ.

PMID- 14577249
TI  - Analysis of cytochrome P450 polymorphisms.

PMID- 14577250
TI  - Induction of cytochrome P450 1A (CYP1A) in fish. A biomarker for environmental
      pollution.

PMID- 14577251
TI  - Generation of allelic series in mice by gene targeting.

PMID- 14577252
TI  - [Surgical treatment of nasosinus tumor involving base of the anterior cranial
      fossa].
AB  - OBJECTIVE: To explore the operative approach for nasosinus tumors involving the
      base of the anterior cranial fossa. METHOD: Seven cases with defects, diameter
      less than 2 cm, on the skull base without damage of the duramater were not
      repaired. Other 7 cases with defects, diameter more than 2.5 cm, on both the
      skull base and duramater were covered with frontalis muscle flap or temporalis
      fascia flap. RESULT: Following up 1-8 year. 6 of the 11 malignant tumors survived
      after 3 years and 2 cases did after 4 years; 3 cases of benignant tumors are
      still alive, neither meningoephalocele nor cerebrospinal fluid fistula and
      extracranial or intracranial infection occurred. CONCLUSION: This operative mode
      is closer to the tumor and easy to repair duramater and stop bleeding, and has
      fine exposure of every nasal sinus, minimal retraction of the frontal lobe. If
      diameter of defect is more than 2 cm on the skull base, the reconstruction is
      necessary.

PMID- 14577253
TI  - [Exploring of surgery solution for chronic sinusitis treatment and application of
      partial middle turbinectomy].
AB  - OBJECTIVE: To explore the effective surgery solution for chronic sinusitis
      treatments and the effect of partial middle turbinectomy which excise the head of
      middle turbinate in treating chronic sinusitis. METHOD: The chronic sinusitis
      patients were divided into three groups due to its cause and its specific ill
      state, each group was treated with suitable surgery solution. RESULT: Thirty-nine
      were cured and 4 improved of 43 sides in the first group. 69 were cured, 10
      improved and 2 ineffective in 81 sides for the second group. 17 were cured, 9
      improved and 5 ineffective in 31 sides for the third group. The collective
      statistics showed that 80.6% were cured and the total effective rate were 95.5%.
      CONCLUSION: Different surgery solutions can be chosen in the treatment of chronic
      sinusitis based on its cause and its specific ill state, and partial middle
      turbinectomy have important effect.

PMID- 14577254
TI  - [Analysis of complications in functional endoscopic sinus surgery].
AB  - OBJECTIVE: Inquiring into the interrelated factors of complications of functional
      endoscopic sinus surgery (FESS). METHOD: The complications of 1,207 FESS were
      reported. The complications were discussed within the fixed indication and the
      resection extent. RESULT: The over/all complications rate was 3.0%. Bleeding and
      periorbital ecchyosis were the common complications, and 1 temporary diplopia, 2
      fever of undetermined origin were found in this group. CONCLUSION: The lower rate
      of complication of FESS is related to limited resection. FESS are a safe
      procedure in experienced hands.

PMID- 14577255
TI  - [Expression of main heat stress proteins and p53 in nasopharyngeal carcinoma].
AB  - OBJECTIVE: To investigate the expression and the significance of main heat stress
      proteins (HSPs) and p53 in nasopharyngeal carcinoma. METHOD: Tissues homogenate
      and western blot were used to determine the level of HSPs and p53. RESULT: HSP27
      and p53 elevated remarkably (P < 0.05) while HSP90 and HSP70 showed no
      significance between nasopharyngeal carcinoma and control tissues. Elevated level
      of HSP27 and p53 don't correlated with histological type and clinical stage.
      CONCLUSION: Expression of HSPs and p53 show some difference in nasopharyngeal
      carcinoma tissue. These data suggest that HSPs and p53 may play a role in the
      development of nasopharyngeal carcinoma.

PMID- 14577256
TI  - [Analysis of the nasal complication after radiotherapy in patients with
      nasopharyngeal carcinoma by logistic regression].
AB  - OBJECTIVE: To study of the risk factors of the nasal complication after
      radiotherapy in patients with nasopharyngeal carcinoma(NPC). METHOD: Observed 131
      cases nasal disease in NPC patients, analyzed the factors that might cause the
      complication by using Logistic regression model. RESULT: The highest incidences
      of complication after radiotherapy was chronic purulent sinusitis (116/131), the
      chosen factors in the regression formula were T staging and radiation for
      anterior field of the nose. The second was nasal synechia(33/131), the chosen
      factors were total dose of external irradiation, intracavitary irradiation and
      medicamentous rhinitis. The incidences of atrophic rhinitis was the lowest
      (9/131), the chosen factors were chemotherapy and medicamentous rhinitis.
      CONCLUSION: T staging of tumor and radiation for anterior field of the nose had
      relation with post radiotherapy sinusitis. It was easy to lead to nasal synechia
      when the does of external irradiation being higher or adding intracavitary
      irradiation or using the decongestant for long time. Chemotherapeutic drugs and
      decongestant may be the risk factors of atrophic rhinitis.

PMID- 14577257
TI  - [The damaged types of eustachian tube function in the patients of nasopharyngeal
      carcinoma after radiotherapy].
AB  - OBJECTIVE: To study the types and the influences of eustachian tube function
      disorder in the patients of nasopharyngeal carcinoma(NPC) after radiotherapy.
      METHOD: Thirty-two patients of NPC (50 ears) that the eustachian tube function
      were damaged after radiotherapy were examined by general examination, audiometer
      test, tympanometry, Tubo-tymanoaerodynamic grapy (TTAG), sonotubometry and
      endoscope. RESULT: Two cases (4 ears) showed abnormal patency of eustachian tube,
      the patients' symptoms were lightly. The eustachian tube adhesion were found in
      five patients(7 ears), and 17 patients(27 ears) showed eustachian tube complete
      obstruction, eight patients (12 ears) showed eustachian tube uncompleted
      obstruction, they had the similitude symptoms. CONCLUSION: The damaged types of
      eustachian tube function in patients of NPC after radiotherapy are different, it
      will harm the ear function. Finding it out will help to choose the treating
      measures.

PMID- 14577258
TI  - [Adenoid cystic carcinoma of the maxillary sinuses].
AB  - OBJECTIVE: To investigate characteristic clinical features and outcomes for
      patients with adenoid cystic carcinoma of the maxillary sinuses (ACC). METHOD:
      Thirteen patients with ACC were treated with a combination of surgery and
      radiation. Prognostic factors were retrospectively analyzed. RESULT: The most
      frequent cause of failure was local recurrence at the primary site. There was no
      neck node failure, 1 patient experienced distant metastases after the treatment.
      The overall disease-free survival rate at 5 years and 10 years were 72.5% and
      54.4%, respectively. CONCLUSION: The symptoms of the ACC occurred in the
      maxillary sinuses are not specific. The early diagnoses are usually difficult.
      Surgeries combined with postoperative radiation are recommended for optimal local
      control and survival. The prognostic factors include the clinic stages of the
      tumor and the resection margins.

PMID- 14577259
TI  - [Effects of taking the pingzhi tablets on cellular infiltration in tissues of
      nasal polyps].
AB  - OBJECTIVE: To assess the effects of taking the "Pingzhi Tablets" on infiltration
      of inflammatory in tissues of chronic sinusitis and nasal polyps. METHOD: Nasal
      polyps from taking the "Pingzhi Tablets" treated patients (40 cases) and
      untreated patients (40 cases) were investigated. The samples were stained by HE
      and SABC-AP immunohistochemical methods. RESULT: Compared with untreated polyps,
      the polyps treated by taking the "Pingzhi Tablets" contained significantly lower
      tissue densities of CD 11b+, CD7+ positive cells. Although the densities of CD
      19+ positive cells were lower in treated polyps, the differences were not
      statistically significant. CONCLUSION: The findings demonstrated tissue effects
      of treatment with taking "Pingzhi Tablets" and the treatment was effective in
      suppressing the inflammatory cell infiltration.

PMID- 14577260
TI  - [Acoustic analysis in different background of hearing].
AB  - OBJECTIVE: To find out the changes of voice in different noisy background by
      computer acoustic analysis. METHOD: Twenty-five young people who got normal
      hearing level and normal vocal cords were selected. They were tested after
      trained. Sustained /a/,/i/ and sentences were recorded in the three different
      background: quite, white band noise and speech noise. The software of MDVP was
      used. Testing parameters included: F0, Jitter, Shimmer, APQ, PPQ, HNR. RESULT:
      Fundamental frequencies of noisy groups are significantly higher in male-/a/,
      female-/a/ and female-/i/ groups. The perturbations are not significantly
      different among them. The HNR is negatively relative with F0. CONCLUSION: Normal
      hearing persons increase their fundamental frequencies in the noisy surroundings.

PMID- 14577261
TI  - [The effects of intranasal FP on the expression of aquaporin-2 in nasal polyps].
AB  - OBJECTIVE: To study the effects of intranasal FP on the expression of AQP-2 in
      nasal polyps. METHOD: Fourteen cases of type II phase 3 and 12 cases of type III
      nasal polyps were selected. FP were intranasally used in 7 cases of type II phase
      3 and 6 cases of type III nasal polyps for 7 days before operation. The others,
      treated with nothing, were used as control. 26 nasal polyps were obtained and
      studied with immunohistochemical technique. RESULT: The volume of nasal polyps in
      FP-using group became smaller. Both the number of AQP-2 positive cells and the
      area density were significantly lower in the FP-using group than in the control
      group (P < 0.01). CONCLUSION: Under the action of intranasal FP the expression of
      AQP-2 reduced, so is the volume of nasal polyps. It indicated that AQP-2
      contributed to edema of nasal polyps and FP may lesson edema through changing the
      expression of AQP-2.

PMID- 14577262
TI  - [Effects of corticosteroid on eosinophils and expression of transforming growth
      factor beta 1 in nasal polyps].
AB  - OBJECTIVE: To observe the effects of systemic steroids on the infiltration of
      eosinophils and the expression of TGF beta 1 in nasal polyps. METHOD: The SP
      immunohistochemical methods were applied to explore the expression of TGF beta 1
      in nasal polyps before and after corticosteroids use; the optical density of
      positive cells in mucosal epithelia, eosinophils, glandular epithelium, vascular
      endothelial, matrix and mucous membrane was measured by using HPIAS-1,000 image
      conduct system. RESULT: The expression of TGF beta 1 was positive in nasal
      polyps. The number of eosinophils and the expression of TGF beta 1 was
      significantly reduced in nasal polyps after treated with corticosteroids compared
      with pre-treated. CONCLUSION: The effects of systemical steroid use on the nasal
      polyps may depend on decreasing the infiltration of eosinophils and the
      expression of TGF beta 1.

PMID- 14577263
TI  - [A study on the application of Nickle-Titanium alloys stent for prevention and
      treatment tracheostomal stenosis after total laryngectomy].
AB  - OBJECTIVE: To evaluate the effect of Nickle-Titanium alloys annular stent to
      prevent and treatment tracheostomal stenosis after total laryngectomy. METHOD:
      The stent was used following total laryngectomy and after total laryngectomy.
      RESULT: Long stent was implanted in 2 cases following total laryngectomy and in 1
      cases after total laryngectomy, Which resulted in widening stenosis and relieving
      obstruction of airway. The tracheostomal diameter is 2 cm afterwards, but the
      patients have crusts, granuloma and stretch feeling in tracheostoma.
      Tracheostomaplasty was performed using short stent in 18 cases during
      laryngectomy. All the cases have no tracheostomal stenosis following over 6
      months. The tracheostoma is smooth, enough larger and stable. CONCLUSION: Nickle
      Titanium alloys annular short stent is fixed outside the wall of trachea, its
      complication is less. It may prevent from tracheostomal stenosis. Nickle-Titanium
      alloys annular long stent is a better method to resolve dyspnea.

PMID- 14577265
TI  - ICD-9 changes and other spooky things.

PMID- 14577264
TI  - [Expression of oncogene C-jun in the cells of rat nasal mucosa and relevance with
      rhinorrhea].
AB  - OBJECTIVE: To study the expression of oncogene C-jun in rat nasal mucosa with
      allergic rhinitis and the relevance with rhinorrhea. METHOD: By using EA to make
      animal model of allergic rhinitis successfully; the amount of rhinorrhea was
      calculated at 30 min. 4 h, 8 h. Immunohistochemical technique, computer image
      analysis technique and histologic examination were used to investigated the
      expression of C-jun in rat nasal mucosa at the same time. The relevance between
      them was used explored. RESULT: There was a lot of C-jun protein at 30 min. The
      difference of C-jun between 30 min group and control group was significant (P <
      0.01) and the relevant coefficient was r = 0.784 (P < 0.05). The C-jun protein
      decreased at 4 h, but there was still significant difference (P < 0.05) and r =
      0.626 (P < 0.05). The C-jun was as same as control group at 8 h, There was no
      difference between them. CONCLUSION: The expression of oncogene C-jun in
      inflammatory cells may be a marker in early stage of activation of inflammatory
      cells, and related to the producing and secreting of cytokines and inflammatory
      mediators in inflammatory cells of allergic rhinitis.

PMID- 14577266
TI  - Solo practice: the way of the future.

PMID- 14577267
TI  - How to get all the 99214s you deserve.

PMID- 14577268
TI  - Leadership is a learned skill.

PMID- 14577269
TI  - 2 tried-and-true tools for E/M documentation.

PMID- 14577270
TI  - Rediscovering the joy of family practice.

PMID- 14577271
TI  - Cost-effectiveness begins between your ears.

PMID- 14577272
TI  - [Comparison of the literature on medical accidents from a medical database and
      articles in daily newspapers in Japan].
AB  - PURPOSE: We analyzed the frequency and content of journal reports on medical
      accidents over the past 15 years, and compared these findings with related
      articles in daily newspapers as a means of assessing medical professionals'
      awareness of current public opinion reflected in daily newspaper coverage.
      METHODS: A search of medical accident reports was conducted using CD-ROM versions
      of the medical literature database Japana Centra Revuo Medicina (1987-2001), with
      the key words "medical accident" and "medical error." The numbers of medical
      accident articles in newspapers and medical lawsuits were taken as indicators of
      public opinion. Relationships were investigated using correlation and time series
      analyses. RESULTS: 1) The total number of reports on medical accidents (including
      medical errors; hereinafter, medical accident reports) in the database was 2,858,
      equaling 0.78 medical accident reports for each 1,000 reports in the CD-ROM
      database. 2) The number of medical accident reports was 174 in 1987, gradually
      increasing to 333 in 2000 and 618 in 2001. 3) The proportion of the reports from
      the nursing field increased from 8.9% (1989) to 31.7% (1999). In contrast, the
      proportion concerning the medical field decreased from 68.8% to 50.2%. 4) The
      number of medical accident articles in two newspapers was investigated. The
      yearly trends were similar in both of these newspapers, showing an increase in
      1999 and a peak in 2000. 5) A review of Supreme Court records revealed that the
      number of medical lawsuits each year increased gradually from 352 in 1990 to 805
      in 2001. 6) There were significant correlations between the number of medical
      accident reports and the numbers of newspaper articles or medical lawsuits. A
      time series analysis of these trends showed that the trend in number of medical
      accident reports was closely linked with those for numbers of newspaper articles
      and medical lawsuits, with a time lag. CONCLUSION: Research trends in papers on
      medical accidents from a database of scientific papers were found to correspond
      with trend curves for medical lawsuits and articles on medical accidents in daily
      newspapers. It was thus demonstrated that awareness of medical accidents among
      medical professionals reflects social emphasis.

PMID- 14577273
TI  - [Study on factors for caries and infant feeding characteristics in children aged
      1.5-3 years in a Kanto urban area].
AB  - PURPOSES: Generally, the incidence of caries in infants is decreasing, but the
      volume for children age 3 at Nakahara Ward in Kawasaki City is nearly 5 times
      higher than that of children at one year and 6 months of age (age 1.5). Here, we
      investigated the risk factors for cariogenesis during the period from age 1.5
      till age 3, focusing on the household environment, lifestyle, diary habits and
      dental hygiene behavior. METHODS: A total of 491 children who had no caries at
      periodical health check at age 1.5 were chosen as subjects from those undergoing
      health check at our Public Health Center. The health check data at ages 1.5 and
      age 3 along with findings from the questionnaire survey at age 3 were analyzed by
      with reference to the presence or absence of caries in children at age 3. Odds
      ratios and 95% confidence intervals (CI95) were first estimated for each risk
      factor to identify those highly correlated to cariogenesis. Then, logistic
      regression analysis was performed after adjustment for mutual correlation among
      the factors. RESULTS: The risk factors significantly correlated to cariogenesis
      during ages 1.5-3 were maternal feeding at age 1.5 (Odds ratio: 2.80, CI95: 1.42
      5.57) and sweet intake of sweets 3 times or more everyday at age 3 (Odds ratio:
      2.07, CI95: 1.24-3.43). Moreover, the lack of nightly teethbrushing by parents
      appeared linked with cariogenesis, (Odds ratio: 1.68, CI95: 0.90-3.14), albeit
      without statistical significance. CONCLUSION: The present results indicate that
      caries is likely to be increased when maternal feeding is prolonged to age 1.5
      and by consumption of sweets more than 3 times a day at age 3.

PMID- 14577274
TI  - [Quantitative analysis of the demand for emergency medicine in Yokohama City,
      Japan].
AB  - PURPOSE: We analyzed regional characteristics that potentially might affect
      regional demand for emergency medicine in Yokohama city and projected the number
      of future ambulance users. METHODS: The number of patients transported by
      ambulance was regarded as an index of the demand for emergency medicine. Various
      factors that may affect regional demand for emergency medicine were used as
      dependent variables in multiple regression analysis. The future population was
      estimated by the cohort change rate method based on the 1995 and 2000 censuses.
      Data pertaining to ambulance use were obtained from the Annual Fire Fighting
      Bulletin, Yokohama. Data pertaining to regional factors were obtained from the
      Annual Health Statistics Report, Yokohama; the Annual Health Statistics Report,
      Kanagawa; and the Statistics Report, Yokohama. RESULTS: Statistically significant
      relations were observed between ambulance use per 1000 population and particular
      regional characteristics, i.e. the proportion of persons undergoing health
      examinations conducted by public health centers, the number of educational health
      promotion programs managed by the public sector, the proportion of persons in
      receipt of livelihood protection, the proportions of roads and commercial areas
      in each district in relation to the total area, the mean land price, the age
      adjusted mortality rate, and the proportion of persons aged 65 years or over. The
      demand for emergency medicine in Yokohama city was predicted to increase
      dramatically as the population ages. The number of patients transported by
      ambulance, which was 121,606 in 2000, was projected to exceed 250,000 in 2030 and
      to approximate 300,000 in 2050. CONCLUSION: The demand for emergency medicine
      will increase dramatically in Yokohama city as the society ages, Regional
      emergency medical systems should be improved accordingly.

PMID- 14577275
TI  - [Fecal weight and its daily fluctuation in young women. Part 2. Related
      parameters].
AB  - OBJECTIVE: In the first part of this survey, we examined the influence of one's
      dietary habits and physical conditions on the frequency of defection and fecal
      weight. We concluded a need for a time series analysis for further investigation.
      In the present supplementary study, we analyzed the correlation between fecal
      weight and nutrient intake, dietary intake and exercise and the daily variation
      in defection and its related aspects. METHOD: The survey was conducted for two 30
      day sessions, during which we amassed data for four 20- to 22-year-old females,
      focusing an eight different parameters, includeing the fecal weight, the number
      of defecations per day, the weight of free-access food items, and kinds of
      dietary intake. We first standardized the measured data: for comparison of the
      date from the two time series analyses, we used the "relative", standardized
      weight, after minimizing the difference between the measured weight and the
      average weight. This allowed examination individual of correlation coefficients,
      for the relation between the two time series, in terms of the cycles of the
      constituents. RESULTS: Time series analysis indicated that variation in fecal
      weight occurs 3- or 4-day cycles with a correlation coefficient higher than 0.7.
      Fecal weight and physical exercise or dietary intake are correlated; the total
      dietary intake over the two previous days is the most important influence
      followed by how much dietary fiber one continues. A correlation with the total
      quantity of water was also found, with lower correlation coefficients for fat
      intake and physical exercise. Regarding relationships between fecal weight and
      dietary compornent: the greatest correlations were with vegetables, followed by
      fruits, cereals, potatoes, and starch in that order.

PMID- 14577276
TI  - [Nationwide survey of municipality's maternal & child health promotion planning
      processes and consequent changes].
AB  - PURPOSE: The purpose of this study was to offer insight into the revisions needed
      for promotion of Maternal and Child Health Promotion Plans in the coming years.
      METHODS: The maternal and child health promotion planning process and changes in
      maternal and child health services were surveyed by questionnaires to all
      municipalities in Japan. RESULTS: Completed questionnaires were obtained from
      2,362 municipalities (response rate: 72.6%) Replies from 2,202 municipalities,
      which had completed planning by March, 1998, were analyzed. Planning committees
      were established by 63.9% of municipalities, and working committees were set up
      in 55.4% of them. Members involved in the working committees were more limited
      when compared to the planning committees and only 9.3% of the committees had
      representatives from mothers. 37.5% of working committees held meetings more than
      5 times. 56.0% of municipalities conducted hearings or questionnaire surveys of
      mothers and health personnel for assessment of maternal and child healthcare
      needs. Most prefectural public health centers provided statistical data for
      planning assistance. Public health center staff participated as planning members
      in 38.5% of municipalities, and a training program for the planning sponsored by
      health centers was utilized by 33.8% of municipalities. Only 18.3% of
      municipalities received support for explanation of the plans to the mayor and/or
      executive officers, only 12.1% received support for the management of the
      planning committees, and only 11.8% received support for needs analysis. Less
      than half of minicipalities conducted PR activities of the plans and progress
      management. A higher proportion conducted these activities in larger cities.
      After the planning process, 72.9% of municipalities started new projects
      according to the plans. However, 10.1% scrapped one or more projects. Changes in
      maternal and child healthcare services and promotion of coordination with other
      related organization were seen more in municipalities with a larger population.
      There were major differences found between prefectures with regards to the
      planning process, including the support from public health centers, and the
      effective use of plan reports, progress management, and changes in maternal and
      child healthcare services after the formulation of plans.

PMID- 14577277
TI  - [An investigation of the experiences of hearing-impaired people undergoing
      medical examinations in health-checkups].
AB  - OBJECTIVE: The end purpose of this research is to ascertain modifications that
      are needed in order to provide an environment in which hearing-impaired people
      can receive health-checkups equivalent to those received by people with normal
      hearing. The problems experienced by hearing-impaired person when undergoing a
      health consultation was thus investigated and differences in the requirements of
      deaf people and those with impaired hearing were also examined. METHODS:
      Questionnaires were completed by 250 members of the Tokyo Federation of the Deaf
      and 100 members of the Tokyo Association for the Hard of Hard of Hearing. Areas
      investigated included, the person's history of health-checkups, aspects of
      medical examinations found to be inconvenient, communication that occurred during
      medical examinations, communication that a hearing-impaired person experts of a
      hospital, and methods by which hospitals could ensure information was understood.
      Responses to questionnaires were compared between the members of Tokyo Federation
      of the Deaf and the members of Tokyo Association for the Hard of Hearing.
      RESULTS: Of 151 subjects enrolled in the present study, 56 were male and 96 were
      female (2 did not reveal their gender). Respondents were aged between 21-85 years
      (mean 54.8 years), with 50.3% receiving an annual health-checkup. The problems
      described by respondents in the context of a medical examination included; 1) not
      being able to recognize when their turn to be seen had arrived, even if called by
      name, 2) not being able to understand medical information and instructions given
      by healthcare staff. In order to ensure they understood the information given,
      respondents described measures that they wished to see implemented. These
      differed between the 2 organizations, with members of the Tokyo Federation of the
      Deaf wanting information to be provided in both sign language and written form,
      whereas members of the Tokyo Association for the Hard of Hearing wished only for
      written information. CONCLUSIONS: Compared to people with normal hearing,
      relatively few hearing-impaired people receive health checkups. In order to
      ensure that hearing-impaired people can understand the information given, and
      therefore receive maximal health benefits, while reducing the risk of potentially
      harmful mishearing of advice, both sign language and written information are
      required.

PMID- 14577278
TI  - [From the point of view of a Naikan counselor].
AB  - I will portrait of my clinical experience in hospitals with Naikan therapy in
      this short paper. At the first hospital, I mainly took care of alcoholics. I
      initially tried to introduce intensive Naikan, the original form of the method,
      into the therapeutic program of alcoholics. Encountering some stumbling blocks,
      however, I ended up using daily Naikan journals but not intensive Naikan form. At
      the second hospital I worked for, I was able to have the private room for the
      sole use of Naikan therapy thanks to the director's consideration. Using
      intensive Naikan this time, I first worked with alcoholics and their families,
      and then I also worked with neurotics and psychosomatics. In April 2000, I
      finally started to devote myself entirely to working as a Naikan therapist at a
      Naikan center, established by the founder of Naikan, Ishin Yoshimoto. This is a
      revision of my address at the 12th WPA symposium in Yokohama held in August 2002.

PMID- 14577279
TI  - [The present state of Naikan in Japan].
AB  - I. Questionnaires concerning the state of propagation of Naikan therapy:
      comparison between 1984 and 2002 (1) OBJECTIVE: I maintained that Naikan will be
      difficult to introduce unless it is known to and recognized by many researchers
      and therapists at the symposium titled "How Naikan should be introduced" in the
      7th Conference of the Japanese Naikan Society in 1984 and carried out a
      questionnaire survey about how much knowledge about Naikan the respondents had,
      whether they had experienced Naikan or not, and whether they were willing to
      practice Naikan or not in April, 1984. This year, 18 years after the initial
      survey, I conducted a questionnaire survey with the same contents in similar
      subjects to evaluate whether Naikan had become more accepted and better known
      since the previous survey. (2) SUBJECTS: Since I thought that the attitudes of
      young assistant professors have the greatest effect on future trends of
      psychiatry, 80 assistant professors at psychiatric departments of medical schools
      of universities and medical colleges throughout Japan were selected as subjects.
      In the present survey, 80 professors were also included as subjects. Also, 3
      hospitals were randomly selected in each prefecture from medium-sized private
      psychiatric hospitals with 200-300 beds, a size considered to be appropriate for
      practicing Naikan therapy, and the directors of the total of 141 hospitals were
      included in the subjects. II. RESULT AND SUMMARY (1) The response rate increased
      slightly in the assistant professors, more than doubled in the hospital
      directors, and was highest in the professors (67.5%). (2) Knowledge about Naikan
      therapy had scarcely spread among assistant professors since the previous survey.
      However, it markedly spread among hospital directors, and 37.6% of the hospital
      directors surveyed, a nearly 4-fold increase compared with the previous survey,
      were relatively well informed about Naikan. About half (46.4%) of the professors
      had considerable knowledge about Naikan. (3) Most of the assistant professors had
      little experience in the practice of Naikan therapy, but 28.9% of the hospital
      directors, more than double the percentage of the previous survey, had practiced
      or used Naikan. Few professors practiced it. (4) About whether the respondents
      are willing to practice Naikan in the future or not, a greater percentage of the
      assistant professors had no intention to practice it in the future, and the
      percentage of hospital directors who had no intention to practice it also
      increased while the percentage of those who wanted to practice it in the future
      increased simultaneously, showing polarization of the attitude. Of the
      professors, 53.7% hoped to practice it, but its realization was difficult due to
      the lack of cooperation by the staff and the restriction of time. (5) Factors
      that prevented spread of Naikan therapy were: [1] Young assistant professors were
      so preoccupied with their specialties that they took little interest in other
      fields, [2] research subjects of assistant professors are recently titled
      markedly to biological fields, [3] Naikan therapy is difficult to be accepted by
      young researchers because of the immaturity of its theorization, impreciseness of
      its indications, and the difficulty of evaluation of its therapeutic effects with
      the resultant ambiguity of the results, [4] it is difficult to gain support from
      hospital directors, because it is not covered by insurance policies so that its
      practice produces a large economic burden, because the place for its daily
      practice is difficult to secure, and because it requires a long time each day to
      both the patients and instructors. I hope that these factors that prevent
      propagation of Naikan are eliminated one by one and that it comes to be practiced
      worldwide to relieve many people of mental and physical ailments.

PMID- 14577280
TI  - [The application of Naikan therapy in China].
AB  - PURPOSE: To briefly introduce the application of Naikan therapy in China. METHOD:
      Naikan therapy of one-day-type was adapted towards 1,226 out-patients of
      neurasthenia diagnosed according to ICD-10, with a neurotic factor higher than
      norm obtained by means of Eyesenck personality questionnaire (Chinese version of
      EPQ-RSC). For each visit, the one-day-type Naikan therapy would need 8 hours,
      with a noon break of an hour for lunch. At the final hour of each visit, the
      patient would say their own thought to the therapist and receive advice. The
      therapy for a common case would need 1 visit to 5 visits, with a week between two
      consecutive visits. For a few cases, 10 visits were needed. RESULT: The mood of
      the patients was obviously improved through Naikan therapy. Among the 248 out
      patients with a relatively complete personal data and a L-score lower than norm,
      111 out-patients (44.76%) with a N-score higher than norm before therapy, 40 out
      patients (16.13%) with a N-score higher than norm post therapy. CONCLUSION: The
      Naikan therapy showed its effectiveness in improving the neurotic factor as well
      as mood of the patients.

PMID- 14577282
TI  - [Philosophical concept and practice of psychiatry: their introduction by a
      symposium planner].

PMID- 14577281
TI  - [The current situation of the internationalization of the Naikan therapy].
AB  - In Japan, there are 27 Naikan medical institutions in which are included 5
      clinics, 5 general hospitals and 17 mental hospitals. As for Naikan meditation
      center, there are 32 places. Generally, Naikan medical institutions and Naikan
      meditation center coexist in Japan. It is rare to see institutions for Naikan
      therapy in more north than Kanto area. Around Nara prefecture, which is Naikan
      therapy cradle, fairly numbers of Naikan meditation center are located.
      Surprisingly, no Naikan medical institutions are located. Naikan medical
      institutions and Naikan meditation center are distributed over the world. Total
      Naikan medical institutions are 32 and it only located in Japan and China. Total
      Naikan meditation center are 38 and 32 in Japan, 3 in Austria, 2 in Germany, and
      1 in U.S.A. I would like to make suggestions as follows. At first, it is
      important to make cooperating with Naikan medical institution and Naikan
      meditation center. Also, it is necessary to enhance the technique ability of
      Naikan therapy. Secondary, we should guide medical workers to make understand
      useful of Naikan therapy as many as possible. Third, in order to do so, it is
      desirable to establish international Naikan Medical Association. Fourthly, it is
      necessary to systematize theory of the disease, therapeutic theory and
      therapeutic mechanism in Naikan therapy.

PMID- 14577283
TI  - Anthropology and psychiatry.

PMID- 14577285
TI  - Mind-body concepts and mental illness: a study of Japanese values.
AB  - This paper examines Japanese mind-body concepts and attempts to tease out some of
      the ways this philosophical orientation influences the Japanese view of mental
      illness. An analysis of key Japanese words will demonstrate that traditionally
      the Japanese have viewed the mind and body as inextricably intertwined and that
      this interconnectedness extends to the Japanese self conceptualization. It is
      argued that this Japanese value orientation sheds light on the stigma associated
      with mental illness and equally helps to explain the Japanese tendency to
      somatisize psychological distress. Because "mental" illness is perceived as a
      character weakness, "somatic talk" becomes a culturally coded idiom of distress
      providing the Japanese with a culturally acceptable way to influence the behavior
      of others while at the same time avoiding being labeled with a psychiatric
      disorder. Somatization in Japan, then, can be understood as an inherently ethical
      event that has more to do with morals than medicine.

PMID- 14577284
TI  - Rebuilding reality: a phenomenology of aspects of chronic schizophrenia.
AB  - Schizophrenia, like other "pathological" conditions, has not been systematically
      included in the general study of consciousness. By focusing on aspects of chronic
      schizophrenia, we attempt to survey one way of remedying this omission. Some
      basic components of Edmund Husserl's phenomenology of human experience
      (intentionality, constitution, and unbuilding) are explicated in detail, and
      these components are then employed in an account of exemplary aspects of chronic
      schizophrenia. We maintain that in schizophrenic experience some very basic
      constituents of reality--constituents so basic we call them "ontological"--are
      lost so that the patient must try to explicitly re-constitute those ontological
      features of the world. Using Husserl's concepts such experiences are described as
      a weakening of "automatic mental life" so that much of the world that is normally
      taken-for-granted cannot continue to be so. This requires the patient to actively
      busy him or herself with re-laying the ontological foundations of reality.

PMID- 14577287
TI  - [Structuralistic and meta-psychological approaches to ambivalence in
      schizophrenia].
AB  - The word "ambivalence" generally signifies a psychic state in which a subject
      holds a contradictory or conflicted attitude towards an object. The literal
      meaning of the word is that two valences occur simultaneously, and this connotes
      the epistemological and ethical problem of where and how the valences arise. The
      concept of ambivalence implies that the relationship between the subject and the
      world is ambivalent, that the subject has free will in the alternative
      evaluation, and that the meanings of the two valences derive from the meta-level
      outside the world. These reflections lead us to the supposition that ambivalence
      is closely associated with the function of language. The ambivalent attitude of
      the subject divides the significance of the object; the appearance of the given
      ambivalent meanings is the moment of the subject's choice. This phenomenon of
      division, choice, and given meanings is more than analogous to F. de Saussure's
      conception of language in terms of sign, differenciation, and l'arbitraire de
      langue. A view of ambivalence as a fundamental phenomenon concerning subject,
      world, and language affords insight specifically into ambivalence in
      schizophrenia. For people with schizophrenia, ambivalent conflict often takes the
      form of a dichotomy between "good and bad". The more severe the ambivalent
      symptom, the more similar it seems to a philosophical question about the nature
      of existence in the world. When schizophrenic people raise philosophical
      questions directly such as "Is my existence good or bad?" or "To be or not to
      be?", they seek approval for their existence, assaying to live with "good"
      intentions. Unfortunately they come to be blamed for harbouring "bad" intentions.
      When they have an interrogative attitude even to everyday matters, they cannot
      resolve such questions as "Is the red cup good or bad?", or "Is the green cup
      good or bad?", and hence "Which cup should I use?". If the projection of the self
      into the world is essentially the choice of a daily behavior as its own praxis,
      such indecisiveness thus entails existential conflict. The alternatives of choice
      appear before them as a tollgate to the world. Wishing admission to the world,
      they choose the thing that they think "good", but which later turns out to be
      "bad". These consequences sometimes occur in their inner conflicts and sometimes
      in their paranoidhallucinatory experiences. We have observed that in these
      processes, there is an inversion between "good and bad", and "bad" predominates,
      driving patients to despair. Rethinking E. Bleuler's conception of the
      ambivalence of schizophrenia, we have found that it is accessible to
      structuralistic and meta-psychological interpretations. From the viewpoint of
      linguistic semiology, ambivalence can be considered as a disorder of exclusive
      differentiation in the associative system resulting from the appearance of
      antithetical meanings, a phenomenon that is also common in primal words and
      children's thinking. In the context of psycho-analysis, it is suggested that the
      dominance of the negative side in ambivalence may be caused by death instinct.
      These interpretations are consistent with both the philosophical considerations
      and the clinical observations introduced above, but the problem of schizophrenic
      specificity is still opened beside the affinity between philosophical conflict
      and schizophrenic ambivalence. References to ethical and philosophical thinking
      shed light on the sources of the dichotomous existential conflict and the
      characteristic inversion between "good and bad" that schizophrenic patients
      experience. Descriptions of the root of ambivalence can be traced back to ancient
      times. In the Ecclesiastes of the Apocrypha, Jesus, son of Sirach, elucidates the
      fundamental ambivalence of will, teaching that the subject has the power of its
      own choice: at its most extreme, the choice between life and death. In the modern
      age, L. Wittgenstein offers a strict description of this ambivalence in his
      "Notebooks 1914-1916". Wittgenstein doubted the possibility of pure subjectivity
      without individual will and furthermore argued that the will is either good or
      evil, that is, the bearer of good and evil. In his view, good and evil are
      somehow connected with the meaning of the world, and meaning ("Sinn" in German)
      is discerned from significance ("Bedeutung" in German). He went on to write that
      the meaning does not lie in the world but outside it. As K. Shingu has noted,
      Wittgenstein's conception is essentially consistent with psycho-analysis. The
      subject recognizes the world with ambivalent will, the world appears with
      ambivalent significance, but its ambivalent meaning is given from outside the
      world, that is, from the meta-level. For E. Husserl's concept of intentionality,
      it is said that the fundamental disorder of schizophrenia is a preverbal or pre
      predicative problem that is connected with intentionality. Yet one wonders
      whether or not pure, neutral intentionality is really possible. Presumably,
      intentionality has an intrinsic ambivalence, since the fundamental relationship
      between the subject and the world may itself be ambivalent. When one becomes
      conscious of a thing, the potential exists to divide one's intentionality between
      "good and bad", and the thing thus appears as "good" or "bad". In the healthy
      psyche, this intrinsic ambivalence emerges only in ethical or philosophical
      thinking. In schizophrenia, however, the ambivalence of intentionality is
      explicitly engaged in diverse situations. The inversion of "good and bad"
      observed in the clinical context signifies that the will of the patient shifts
      from "good" to "bad", alluding to a contradiction between the subject and the
      world that is logically inevitable due to the structure of their relationship.
      The subject objectivfies the world positively, yet is contained by the world
      passively. That the subject simultaneously announces and is announced in the
      language system also reflects this paradoxical relationship. Thus, ambivalence of
      dichotomy between "good and bad" is the very basic phenomenon of consciousness,
      and the inversion of "good and bad" is a reflection of the structure of the
      relationship of the subject and the world. If the schizophrenic specificity
      exists, it may involve the exposure of this intrinsic ambivalence and this
      paradoxical structure in confrontations with the tellgate into the world under
      the dominance of the negative side.

PMID- 14577286
TI  - The notion of subjectivity in psychopathology.
AB  - The aim of this essay is to show that a dialectically shaped theory of
      subjectivity is necessary for psychopathology. After introductory remarks about
      the tasks of psychopathology in general a critique of the so-called
      "anthropological psychiatry" leads to the finding that this theoretical framework
      is not sufficient to offer psychopathology a philosophical orientation in accord
      with the needs of our time. By analyzing the meaning of psychopathology the
      special dialectics involved are demonstrated, and a concept of subjectivity is
      elaborated using proposals by the Czech philosopher Milan Prucha.

PMID- 14577288
TI  - [Developmental consideration on the loss of self-evidence (naturlichen
      Selbstverstandlichkeit) in pervasive developmental disorders].
AB  - The "loss of self-evidence" has been noted by many, particularly in our country,
      as a fundamental dysfunction in schizophrenia. Recent recognition of this "loss
      of self-evidence" in personality disorders such as borderline cases, and
      developmental disorders such as autism and Asperger's syndrome is focusing
      renewed interest on this perspective. It is possible that investigation into this
      "loss of self-evidence" noted in the pervasive developmental disorders may
      provide clues into the process of its development and acquisition. This paper
      takes up the issue of "loss of self-evidence" illustrated through the treatment
      process of 2 patients (female, adulthood autism, adolescent Asperger's syndrome)
      the author has treated. The psychopathology of the "loss of self-evidence" seen
      in the pervasive developmental disorders is discussed through these cases in
      terms of development from the standpoint of clinical intervention for
      relationship disturbance. The conclusions are as follows. First, the grave
      psychopathology pertaining to "self-evidence" in the adult autism and adolescent
      Asperger's syndrome cases is discussed, wherein difficulty in controlling one's
      action by one's own will giving rise to serious estrangement between experience
      and consciousness is noted as the pathology held in common by the two. Next,
      through examination of the normal acquisition process of words and language, it
      is shown that the essence of the language disorder seen in pervasive
      developmental disorders lies in the acquisition of meanings of objects being
      based upon the absence of common experience between subject and caregiver. As
      such, words representing meaning and content as we see them are imprinted on such
      individuals, never harmonizing with their own experiential world, giving rise to
      serious estrangement between their experience and consciousness. Third, sharing
      what the child is focusing upon in the outer world and how he/she is relating to
      it in their experiential world, and approaching them with words appropriate to
      their interpretation, is pointed out as being of critical importance in the self
      evidence. In support of this, it is asserted that the establishment of affective
      communication characterized by mutual resonance of body and affect, and the
      development of communication upon this basis will, for the first time, enable
      transmission of culture to such individuals in favorable form, emphasizing the
      exceptional importance of attachment formation (amae) as being the key to this
      process.

PMID- 14577289
TI  - [Delinquency by a juvenile with pervasive developmental disorder: a case in which
      interaction between disorder and family dysfunction played a key role].
AB  - Pervasive Developmental Disorder (PDD) is characterized by peculiar psycho
      behavioral patterns. Youths with PDD who commit delinquent acts often exhibit
      strange behavior beyond ordinary comprehension. In order to fully understand and
      identify PDD it is important to take a comprehensive psychosocial history. Here
      we report on a 19-year-old delinquent male from a juvenile detention home who was
      exhibiting PDD. Both the psycho-behavioral patterns of the subject and the
      dysfunctional family background were key factors in this case. The subject
      persistently stalked and harassed an elementary school girl despite repeated
      intervention by police and the girl's parents to stop doing so. This behavior
      culminated in the subject being arrested and put on probation. While on probation
      his behavior continued, leading to his arrest and confinement to a correctional
      facility for juveniles with medical needs. Several features that included
      sustained impairment in social interaction and repetitive patterns of behavior
      that are often identified in delinquents with PDD were found to exist in the
      subject and he was diagnosed with PDD (probably Asperger's disease). The subject
      presented with a superficial understanding of the consequences his behavior had
      on others and for himself. Also, impaired family function was found to be a major
      contributing factor to his delinquency. Together theses factors hindered the
      subject from acquiring appropriate social skills. The major responsibility for
      providing care and support of an individual with PDD is within the family.
      Failure of the family to undertake such responsibilities can lead to ineffective
      treatment even after a specialist has identified the disorder. Given the slow
      decline of the nuclear family in Japan, it is important to understand the role of
      the family in caring for a child with PDD. Also, public recognition of PDD and
      social support for individuals with the disorder is important.

PMID- 14577290
TI  - [Acute thromboembolism and the related organs].

PMID- 14577291
TI  - [Acute pulmonary thromboembolism--prologue].
AB  - For a long time, the studies of acute pulmonary thromboembolism in Japan have
      been focused on its early diagnosis and the rescue of the patients. However, the
      recent trends in the trials in the courts or the headlines in the newspapers have
      indicated that the major public interests are directed to its primary
      prophylaxis. Thus, the guidelines for the prophylactic strategy of acute
      pulmonary thromboembolism are needed today. It would be important to know (1) to
      what extent the thrombotic tendency should be examined, (2) how the patients with
      the risk could be identified, (3) which prophylactic interventions should be
      selected, and finally (4) what are the expected cost-benefit effects. An emphasis
      should be put on that the researches to derive quantitative estimates of the
      risks of thromboembolism and the studies of the efficacy of each of the
      prophylactic interventions in Japanese patients would provide the basis of such
      guidelines.

PMID- 14577292
TI  - [The epidemiology of acute pulmonary thromboembolism].
AB  - In contrast to the decreasing incidence of pulmonary thromboembolism in Western
      countries, the incidence examined as determined by autopsy, vital statistics, and
      clinical surveys is increasing in Japan. The combination of these data indicates
      the possibility of low diagnostic ability in Japan. The causes of the disease and
      the predictors of in-hospital death are summarized. The most popular congenital
      coagulopathies in Western countries, factor V Leiden and prothrombin G20210A
      mutation, have not been found in Japan. But recent reports showed that
      coagulopathy might have a greater contribution to the occurrence of the disease
      than was previously thought. We introduce reports that show a relation between
      the disease and life style.

PMID- 14577293
TI  - [Postoperative pulmonary thromboembolism].
AB  - Since 1986, American College of Chest Physicians (ACCP) has been regularly
      releasing guidelines for antithrombotic therapy for prevention and treatment of
      thrombosis. The sixth ACCP consensus 2001 conference has recommended successful
      prevention strategies in surgical patients. A few Japanese prospective studies
      disclosed that the incidence of deep vein thrombosis(DVT) after general surgery
      in Japan is about half in western countries. On the other hand, it is reported
      that the incidence of DVT after total hip replacement and total knee replacement
      in Japan is almost as same as in western countries. Since there is still little
      data available for the incidence of postoperative DVT and pulmonary
      thromboembolism in Japan, it is necessary to organize some prospective
      multicenter surveys for them.

PMID- 14577294
TI  - [Risk factors].
AB  - By entrances to facilities, injury, invasions of the operation, and complication
      as cancer, etc., a crisis risk remarkably increases on pulmonary embolism
      thrombosis(PE). As risk factors of thrombosis except for above, abnormal protein
      C, abnormal protein S and abnormal antithrombin are often observed. Caucasians
      have frequently FV Leiden or abnormal FII as congenital thrombophilia, though
      those are not observed to Japanese. As an acquired risk factor for PE, there are
      cancer, high homocysteinemia, lipid abnormality and anti-phospholipid antibody
      syndrome. It is necessary to evaluate these risk factors for the prevention of
      PE.

PMID- 14577295
TI  - [Haemostatic molecular markers].
AB  - Because a significant number of the deaths caused by acute (massive) pulmonary
      thromboembolism occur within the hours after the onset of symptoms, its early
      diagnosis is very important. The gold standard diagnostic tests for venous
      thromboembolism (VTE), contrast venography and pulmonary angiography,
      respectively, are invasive, expensive, not readily available, and labor
      intensive. A diagnostic tool for VTE is needed that is noninvasive and highly
      accurate, allowing immediate treatment decisions to be made in most cases. D
      dimer, a one of haemostatic molecular markers, is specific cross linked fibrin
      derivatives. This is the most promising blood test for VTE screening. Although
      elevated concentrations of D-dimers are sensitive for the presence of VTE, they
      are not specific. They therefore cannot be used to make a positive diagnosis of
      VTE.

PMID- 14577296
TI  - [The role of echocardiography and venous ultrasonography in the diagnosis of
      acute pulmonary thromboembolism].
AB  - Patients with pulmonary embolism (PE) are undergoing echocardiography and venous
      ultrasonography with increasing frequency. Echocardiography is ideal because it
      is readily available and is useful for the differential diagnosis in
      hemodynamically unstable patients. Although predominantly employed to
      characterize RV pressure overload, echocardiography may detect right heart
      thrombus or may provide alternative diagnosis. Echocardiography also is useful in
      assessing the prognosis of patients as well as their response to therapy. Right
      ventricular hypokinesis, a patent foramen ovale, and right heart thrombus are
      markers identifying patients at risk for death. PE and deep vein thrombosis are
      different clinical manifestations of a common disease entity. Venous
      ultrasonography may reduce pulmonary angiography in patients with non-diagnostic
      lung scan.

PMID- 14577297
TI  - [Lung scintigraphy and CT. MRI].
AB  - Helical CT became a reliable tool for diagnosing acute pulmonary thromboembolism
      (APTE) together with lower extremity ultrasound, though lung scintigraphy is
      still popular test for surveying and following the patients for APTE. Novel
      technology of multi-slice CT enabled us to obtain images on thinner slice
      thickness with better contrast. Development of workstation helped us to analyzing
      3-dimensionally as well as providing useful 3D images quickly. CT venography,
      additional scan for surveying deep venous thrombosis, was utilized as an
      effective and time-saving technique. These condition should improve diagnostic
      accuracy of CT. MRI was proposed to be a promising tool for diagnosing APTE in a
      noninvasive manner.

PMID- 14577298
TI  - [Intravascular ultrasound and angioscopy].
AB  - We observed pulmonary artery thrombi and parietal lesions in patients with acute
      pulmonary thromboembolism (APTE), using intravascular ultrasound (IVUS) and
      angioscopy (AS). In APTE without underlying disease mainly non-echorich
      intraluminal mass was noted, with a pulsatile and thin intima. On AS red thrombi
      with white fibrin coating could be directly observed, and no parietal lesions
      were found. The findings of the pulmonary arterial intima and thrombus were
      different between APTE and chronic pulmonary thromboembolism (CPTE), and even
      among CPTE cases. IVUS and AS are useful in characterizing the thrombi and
      related pulmonary artery lesions in PTE.

PMID- 14577299
TI  - [Pulmonary angiogram in the diagnosis of acute pulmonary embolism].
AB  - The indication, complication, diagnostic finding, pit fall of pulmonary
      angiogram(PAG) for the diagnosis of acute pulmonary embolism (PE) were described.
      Current non-invasive test such as V/Q scan, CT and MR have been accepted as
      useful tools for diagnosis and decision making of the treatment of PE. The
      indications of PAG seems to be limited as the cases with 1) discrepancy between
      clinical findings and the results of V/Q scan, 2) high suspicious of PE with some
      risk of anti-coagulant therapy or presenting complication of this therapy, 3)
      prior to IVR. However, the PAG is still accepted as final clinical test to make a
      decision of PE or not.

PMID- 14577300
TI  - [An update consideration for the use of antithrombotic agents].
AB  - Despite recent introduction of catheter-based invasive strategy, the mainstay of
      the treatment for acute pulmonary thromboembolism is antithrombotic medication.
      The most standard tactics is to start intravenous unfractionated heparin (for a
      better substitute, low-molecular-weight heparin is available overseas), and to
      shift it to oral warfarin and maintain for at least 3 months. The duration of
      prophylactic anticoagulation may be extended longer by weighing the risks of
      recurrence and anticoagulant-related bleeding. Use of fibrinolytic agents should
      be considered first of all in patients who have hemodynamic instability or
      cardiogenic shock (massive type), because its effects are rapid and drastic in
      many cases. Recent evidence suggests that fibrinolytic therapy be also effective
      in patients with right ventricular pressure overload and dysfunction (sub-massive
      type).

PMID- 14577301
TI  - [Endovascular treatment].
AB  - Acute pulmonary thromboembolism is a common condition with non-specific findings,
      high mortality, and multiple therapeutic options. Death in patients with acute
      massive pulmonary thromboembolism is caused by sudden circulatory collapse as a
      consequence of obstructed pulmonary blood flow. Initial therapy must therefore be
      directed toward quickly restoring pulmonary circulation. In a number of cases,
      thrombolytic therapy may fail to achieve this therapeutic goal in time.
      Percutaneous catheter treatment may represent an additional option for high-risk
      patients. In this paper, different concepts of such treatment include pigtail
      catheter thrombectomy and embolus aspiration with PTCA guiding catheter are
      described.

PMID- 14577302
TI  - [Surgical treatment for acute massive pulmonary thromboembolism].
AB  - Acute massive pulmonary thromboembolism is a life threatening disorder that must
      be treated immediately. We performed emergent pulmonary thrombectomy using
      cardiopulmonary bypass on 15 patients. The patients were 7 men and 8 women aged
      28 to 81 years. Early diagnosis was made by body CT scan and echocardiography.
      When patient had massive pulmonary thromboembolism, when hemodynamics could not
      be improved by medical treatment, direct embolectomy was performed immediately.
      12 patients developed shock and 8 patients underwent cardiac massage. Among 15
      patients, 11 were saved by surgical treatment, while the remaining 4 died of
      multiple organ failure, cardiac failure and mediastinitis. The lives of patients
      with acute massive pulmonary thromboembolism can be saved by early detection and
      emergent thrombectomy using cardiopulmonary bypass.

PMID- 14577303
TI  - [The inferior vena caval filter to prevent from an onset or a recurrence of acute
      pulmonary thromboembolism].
AB  - Patients suffered from APTE(acute pulmonary thromboembolism) are mainly treated
      with anticoagulation therapy. IVCF(the inferior vena cava filter) is a device to
      prevent the occurrence and recurrence of APTE. The use of IVCF as a treatment of
      thromboembolic disease applies fundamentally for patients of the less efficacy
      and contraindications to anticoagulation. IVCF is effective for short-term
      protection of APTE than anticoagulation therapy alone. Mortality from filter
      placement appears to be quite low, regardless of which filter is used. The
      majority of clinically important complications appear to involve venous
      thrombosis at the insertion site and the inferior vena cava obstruction in long
      term, therefore the short-term temporary IVCF is useful and it requires further
      follow-up data.

PMID- 14577304
TI  - [General surgery].
AB  - Perioperative prophylaxis for pulmonary embolism (PE) is now an emerging issue in
      Japan because its frequency is increasing very rapidly. Although the optimal
      prophylaxis should be performed individually on the basis of clinical evidence,
      the available data on the incidence and prophylaxis of PE are limited in Japanese
      surgical patients. Both mechanical and pharmacological methods of prophylaxis
      have been developed. Intermittent pneumatic compression (IPC) appears to be
      effective. The importance of thromboprophylaxis with anticoagulants including
      heparin is also emphasized. A new guideline for PE prophylaxis is expected to be
      established based on Japanese clinical evidence.

PMID- 14577305
TI  - [Obstetrics and gynecology].
AB  - Pregnancy has been recognized as a predisposing risk factor of deep venous
      thrombosis(DVT) and pulmonary thromboembolism(PTE). Recently, we investigated the
      incidence of PTE between 1991 and 2000 among 64 facilities of Obstetrics and
      Gynecology in Japan. As a result, incidences of PTE are 0.006% (14/227,318) in
      cases of vaginal delivery and 0.046%(25/54,277) in cases of cesarean section (CS)
      in Obstetrics. In Gynecology, they are 0.03% (34/106,598) in patients of benign
      tumors and 0.33%(54/16,206) in patients of malignant tumors. Classification of
      level of risks in Japanese subjects at present is thought to be as follows; cases
      of normal delivery and minor surgery are low risk, cases of CS and benign
      gynecological tumors are moderate risk, cases of CS with elderly fatty pregnant
      women and gynecological malignant tumors are high risk, and cases of CS or
      malignant tumors with thrombophilia or pre-DVT are the highest risk. Prophylaxis
      of DVT should be recommended early ambulation and adequate hydration in low risk
      cases, graduated compression stocking (GCS) or intermittent pneumatic compression
      (IPC) in moderate risk cases, IPC or the use of low-dose unfractionated
      heparin(LDUH) (and/or GCS) in high risk cases, and LDUH and IPC or LDUH and GCS
      in the highest risk cases.

PMID- 14577306
TI  - [Orthopedic surgery].
AB  - The incidence of proximal deep venous thrombosis after total hip or total knee
      replacement and surgery of hip fracture in patients in Japan is more than 10%,
      and intermittent pneumatic compression (foot pump) or anticoagulation therapy
      should be performed after these surgeries to prevent venous thromboembolism.
      Early surgery and early walking exercise are most effective prophylaxis of venous
      thromboembolism for patients with hip fracture. The incidence of proximal deep
      venous thrombosis after spine surgery is low, and that of deep venous thrombosis
      after general surgery of lower extremity is nuclear, and gradual compression
      stockings or foot pump should be performed after these surgeries.

PMID- 14577307
TI  - [Prevention of pulmonary thromboembolism in medical patients].
AB  - In contrast to surgical patients, prevention of acute pulmonary thromboembolism
      has been less well studied in hospitalized medical patients even in Western
      countries. But some data apparently showed the high prevalence of venous
      thromboembolism in medical patients. The combination of mechanical prophylactic
      measures should be indicated for medical patients with risk factors including
      stroke, cancer, prolonged bedrest, heart failure and severe lung disease.
      Prospective studies to evaluate the frequency of venous thromboembolism in
      medical patients with risk factors and the efficacy and safety of each
      prophylactic measure, especially of pharmacological prophylaxis are necessary to
      establish the guidelines for prevention of pulmonary thromboembolism for Japanese
      people.

PMID- 14577308
TI  - [Economy class syndrome].
AB  - Economy class syndrome is venous thromboembolism following air travel. This
      syndrome was firstly reported in 1946, and many cases have been reported since
      1990s. Low air pressure and low humidity in the aircraft cabin may contribute to
      the mechanism of this syndrome. Risk factors for venous thrombosis in the plane
      were old age, small height, obesity, hormonal therapy, malignancy, smoking,
      pregnancy or recent parturition, recent trauma or operation, chronic disease and
      history of venous thrombosis. In Japan, the feminine gender is also risk factor
      though reason was not well known. For prophylaxis, adequate fluid intake and leg
      exercise are recommended to all passengers. For passengers with high risk,
      prophylactic measures such as compression stockings, aspirin or low molecular
      weight heparin should be considered.

PMID- 14577309
TI  - [Guidelines for prevention of venous thromboembolism in the West and Japan].
AB  - Venous thromboembolism has been a common illness even in Japan and gets increased
      social as well as medical attention, especially during postoperative period,
      while guideline for prevention of the disease has been available in the West.
      Since the clinical experience has shown that there are ethnic differences between
      Japanese and westerners in coagulability, we need a Japanese own guideline. The
      guideline based on experts' views in Japan has been formulating, although it is
      difficult to prepare an ideal one based on reliable evidences for Japanese at
      present. We expect this first guideline be the foundation for establishment of an
      ideal one.

PMID- 14577310
TI  - [Problems in digestive system diseases treated within the framework of the
      National Health Insurance coverage--chronic gastritis and gastric ulcer:
      discussion].

PMID- 14577311
TI  - [NF kappa B decoy for clinical applications].
AB  - Recent progress in DNA technology, such as antisense oligodeoxynucleotides (ODNs)
      to regulate the transcription of disease-related genes, has important roles in
      therapeutic applications. Recently, transfection of cis-element double-stranded
      DNA, named as 'decoy', has been reported to be a useful method for gene therapy.
      This 'decoy' strategy has been not only a useful method for the experimental
      studies of endogenous gene regulation but also a novel clinical strategy for gene
      therapy. In this article, we reviewed (1) experimental results from the several
      disease models, (2) the ongoing clinical trials including coronary angioplasty,
      arthritis, and dermatitis in Japan.

PMID- 14577312
TI  - [What is 'metabolic domino effect'?--new concept in lifestyle-related diseases].
AB  - Lifestyle-related diseases such as hypertension, hyperlipidemia, and impaired
      glucose tolerance are independent risk factors for cardiovascular diseases. When
      these risk factors accumulate, the risk of cardiovascular diseases remarkably
      increases. This condition, marked by an accumulation of these risk factors in one
      person, is considered a disease entity by itself called the 'metabolic syndrome'.
      The effects of this syndrome over time are now being referred to as 'metabolic
      domino effect'. This new concept considers factors such as the flow of time and
      the chain reaction of the risk factors. When these risk factors accumulate in one
      person over time, the risk factors interact and multiply the cardiovascular risk,
      leading to a process similar to falling dominoes; once the process begins, it
      leads to cardiovascular diseases that are irreversible. Data strongly suggests
      that angiotensin II is a contributing factor at every step of the process in this
      metabolic domino effect, starting from obesity to the progression of
      macroangiopathy and microangiopathy. The key to effectively preventing
      cardiovascular diseases is to suppress production of angiotensin II at an early
      stage of the metabolic syndrome.

PMID- 14577313
TI  - [Acquired inhibitor against coagulation factor V with severe hematuria].
AB  - A 42-year-old man was admitted with hematuria after a common cold. No purpura
      could be observed but there was oozing on the site of the forearm where blood had
      been taken in a previous hospital. Platelet count was 292 x 10(3)/microliter,
      examination of coagulation system showed abnormalities; prolonged prothrombin
      time: PT (99.7 sec) and activated partial thromboplastin time: APTT (more than
      200 sec), which suggested deficiency of coagulation factor II (FII), factor V
      (FV) or factor X (FX). In fact, the FV activity was only 2% of the pooled normal
      plasma. Mixing test of patient's plasma with normal pooled plasma revealed the
      existence of an FV inhibitor (FVI), which was IgA with an activity levels of 3
      Bethesda unit/ml. Although hematuria stopped soon after beginning treatment with
      steroids (PSL), the abnormalities in PT and APTT improved very slowly and
      incompletely. At the time of writing, FVI is still observed ten months after
      onset. The patient had no underlying disease, and in this case FVI appeared
      following a common cold. Previous reports have said that FVI can cause mild
      bleeding, and it disappear in a short time. This case showed the possibility of
      the hidden presence of FVI in patients with hematuria.

PMID- 14577314
TI  - [Abscopal effect of small intestinal NK/T-cell lymphoma].
AB  - The abscopal effect is characterized by the spontaneous regression of
      unirradiated tumors resulting from the effect of irradiation on remote tissue. We
      report a case of NK/T-cell lymphoma of the small intestine that achieved complete
      remission as a result of an abscopal effect. A 74-year-old Japanese woman was
      referred to our hospital because of ileus and suspected perforation of the
      gastrointestinal tract. An emergency operation was performed and a perforated
      ulcerative tumor in the small intestine and enlarged mesenteric lymph nodes were
      found. Histopathological examination of the resected small bowel showed
      infiltration of large lymphoid cells with irregular nuclei and they were positive
      for CD3, CD56, TIA-1 and granzyme B. Physical examination did not reveal any
      lymphadenopathy in the neck, axillary or inguinal regions, skin involvement or
      nasal infiltration. The CT scans revealed multiple tumors in her upper abdomen
      and an obstructing conglomerate of small intestinal tumors. The patient did not
      show any response to CHOP therapy and radiotherapy was delivered to the lower
      abdominal field for the treatment of the ileus at a total dose of 44 Gy. Two
      months after radiotherapy, abdominal CT scans showed the disappearance of not
      only the tumors in the irradiation field but also the upper abdominal tumors that
      had not been irradiated. The patient has remained in complete remission for 15
      months.

PMID- 14577316
TI  - [Isolated granulocytic sarcoma in the breast].
AB  - A 16-year-old female, who was diagnosed as having non-Hodgkin lymphoma following
      a biopsy of a tumor of her right breast, was admitted to our hospital. The
      diagnosis made by the referring hospital was not reconfirmed because of the
      pathological findings with suspicion of sarcoma. As another tumor appeared in the
      contralateral breast 10 days after hospitalization, a second biopsy of the tumor
      was performed. Touch preparations of the tumor were positive for myeloperoxidase
      and naphthol AS-D chloroacetate esterase staining. The diagnosis of granulocytic
      sarcoma (GS) was made. No abnormalities were found in the peripheral blood and
      bone marrow at this time. Chromosomal examination of the bone marrow was normal.
      The number of copies for WT-1 mRNA was high both in the bone marrow cells and the
      tumor cells. The expression of WT-1 mRNA in peripheral blood was not detected.
      She was treated with the same protocol as for acute myelogenous leukemia and the
      breast tumor disappeared. The titer of WT-1 mRNA in bone marrow slightly
      decreased but remained high. Taken together, these findings suggest that the GS
      seems to be bone marrow origin and the monitoring of WT-1 mRNA may be useful for
      early diagnosis of any relapse.

PMID- 14577315
TI  - [Acute myeloid leukemia originating from the same leukemia clone after the
      complete remission of acute lymphoid leukemia].
AB  - A 22-year-old female was diagnosed as having acute lymphoid leukemia (ALL) in
      February 1995, from the findings of peroxidase negative, CD10+, CD19+, TdT+ and
      rearrangement of IgH and TCR beta. AdVP (doxorubicin, vincristine and
      prednisolone) therapy achieved a complete remission (CR). Bone marrow
      transplantation had to be abandoned because of the lack of an HLA-identical
      donor. Intensification therapy was thus carried out repeatedly. In June 1998,
      myeloblast with Auer rods, peroxidase positive, CD13+, CD33+ and HLA-DR+,
      appeared. The patient was diagnosed as having lineage switch acute myeloid
      leukemia (AML) from ALL. Though A-DMP (cytosine arabinoside, daunorubicin, 6
      mercaptopurine) therapy was resistant, AdVP therapy led to a CR. The patient died
      of cardiotoxicity from anthracyclines in February 1999. From the results of the
      Ramasamy method using the clonal rearrangements of the Ig heavy chain gene locus,
      the origin of the pathological cells of ALL and AML was indicated to be the same
      leukemia clone.

PMID- 14577317
TI  - [IgM type multiple myeloma expressing various surface adhesion molecules and
      demonstrating an aggressive clinical course].
AB  - A 70-year-old woman was admitted for anemia, elevated serum total protein and a
      right axillary mass. Laboratory data showed monoclonal x IgM with a decrease in
      serum IgG and IgA levels. An occipital punched-out lesion was detected on a
      cranial X-ray. A tumor lesion was detected on chest X-ray and computed
      tomography. Biopsy specimen revealed plasmacytoma with cytoplasmic IgM. Bone
      marrow aspiration revealed an elevated plasma cell count. An immunophenotype
      analysis of the plasma cells showed positivity of cytoplasmic IgM, x, CD5, CD38,
      CD11a (LFA-1), CD44 (HCAM), CD49d (VLA-4) and CD54 (ICAM-1). From the above
      results, we diagnosed the patient as having IgM myeloma associated with
      plasmacytoma. Melphalan and prednisolone therapy were prescribed, their effect on
      the myeloma was short term, so we changed the chemotherapy to VAD (vincristine,
      adriamycin and dexamethasone), but this treatment had little effect. The patient
      developed bacterial pneumonia and died. IgM myeloma is a rare disease and reports
      of immunophenotype analysis are also rare. There is no case report of
      plasmacytoma associated with IgM myeloma.

PMID- 14577318
TI  - [Efficacy and pharmacokinetics of imatinib mesylate in a child with chronic
      myeloid leukemia].
AB  - A 6-year-old girl with chronic myeloid leukemia (CML) was treated with imatinib
      230 mg/m2/day and its pharmacokinetics were investigated. The patient had a
      complete hematologic response on day 21, but had a minor cytogenetic response and
      the CML progressed to a blast crisis on day 133. At present, she has maintained
      complete cytogenetic remission with allogenetic peripheral blood stem cell
      transplantation. The pharmacokinetics revealed that the maximum concentration
      (1.4 micrograms/ml); time to maximum concentration (5.1 h); half-life (11.0 h);
      trough concentration (0.4 microgram/ml); and, area under the concentration-time
      curve (28.1 micrograms.h/ml) were inferior to those for adult patients in the 400
      mg/day group. This observation suggests that a suboptimal plasma concentration
      might be related to resistance to imatinib and/or blast crisis.

PMID- 14577319
TI  - [Unrelated HLA-mismatched cord blood transplantation using nonmyeloablative
      conditioning in an adult patient with very severe aplastic anemia].
AB  - An adult patient suffering from G-CSF-resistant very severe aplastic anemia
      received a cord blood transplantation from a three-loci HLA-mismatched unrelated
      donor after nonmyeloablative conditioning. Cord blood was infused after
      conditioning with fludarabine (180 mg/m2) and cyclophosphamide (100 mg/kg).
      Cyclosporin A and short-term methotrexate were used for prophylaxis against acute
      GVHD. Engraftment was achieved on day 23, and there was no serious GVHD. A full
      donor type T-cell chimerism was obtained by day 30. Normal hematopoiesis and
      complete chimerism have been maintained 14 months after transplantation.

PMID- 14577320
TI  - [Successful treatment of refractory acute GVHD with mycophenolate mofetil after
      peripheral blood stem cell transplantation from the patient's one locus
      mismatched mother].
AB  - A 35-year-old male with chronic myeloid leukemia in the accelerated phase
      received a peripheral blood stem cell transplant from his HLA-DR-mismatched
      mother. Graft-versus-host disease (GVHD) prophylaxis was with short-term
      methotrexate and tacrolimus. After transplantation, grade II skin acute GVHD
      occurred and was unsuccessfully treated with bolus methylprednisolone
      administration. The acute GVHD progressed to grade III of the skin, gut and
      liver, and mycophenolate mofetil (MMF) was accordingly administered at a daily
      dose of 2 g. This treatment resulted in a dramatic improvement in the clinical
      features of the acute GVHD. The patient suffered from hemorrhagic cystitis and
      several episodes of cytomegalovirus antigenemia. MMF may be useful for steroid
      resistant acute GVHD despite an increasing risk of viral infections.

PMID- 14577321
TI  - [Significance of diagnostic imaging in otorhinolaryngology emergencies].

PMID- 14577322
TI  - [Congenital middle ear cholesteatoma: experience in 48 cases].
AB  - We studied 48 patients (48 ears) with congenital cholesteatoma who underwent
      surgery at our department from 1979 to 2000, and investigated symptoms at initial
      onset, tympanic membrane findings, cholesteatoma configuration and site, type of
      surgical procedure, and surgical outcome. Patients were from 2 to 62 years old
      (mean: 16.7 years), with 60.4% aged 15 years or younger. The symptom at initial
      onset was hearing loss in most (58.2%). Hearing loss was the main symptom in all
      with open type cholesteatoma, and most of these patients had normal tympanic
      membrane findings. The cholesteatoma was located mainly in the superior posterior
      portion of the tympanic cavity in many patients. The site of involvement was the
      tympanic cavity in 12 (25.0%), mastoid cavity in 2 (4.2%) and the petrous apex in
      1 (2.1%). In many of (31 ears, 64.6%), the cholesteatoma was advanced and
      extended from the tympanic cavity to the mastoid antrum. For 23 of the 48 ears,
      treatment was completed in one operation. The remaining 25 ears required staged
      surgery. Loss of the structure of the upper part of the stapes was seen in 58.3%
      of patients, so most underwent type IV ossiculoplasty, with types III and I next
      most common.

PMID- 14577323
TI  - [Internet survey of the relationship between vertigo and stress].
AB  - We studied the relationship between vertigo and stress, using an internet survey.
      A questionnaire posted on our homepage quantified and measured 4 categories:
      cause of anxiety, behavioral characteristics, mean of relaxation, and frequency
      of vertigo. There were 6065 responses. Scores for the cause of anxiety were
      significantly greater and scores of means of relaxation were less in older than
      younger respondents. Scores for the cause of anxiety and behavioral
      characteristics were singificantly greater in more frequent than less frequent
      vertigo. Scores for means of relaxation were less in frequent vertigo. These
      findings indicate an intimate relationship between the onset of vestibular
      disorder and stress.

PMID- 14577324
TI  - [Temporal bone study of residual mastoid inflammation in ears with normally
      appearing tympanic membrane].
AB  - We examined 395 temporal bones with an intact tympanic membrane to explore the
      relationship between residual inflammation in the middle ear cavity and
      development of mastoid pneumatization. Histopathological changes were studied in
      the middle ear cavity. Mastoid pneumatization was classified as good or poor
      based on the extent of mastoid tip development to the lateral semicircular canal.
      Specimens were 344 temporal bones with well-pneumatized mastoid and 51 with
      poorly-pneumatized mastoid. Otitis media was noted in 119 (34.6%) bones in the
      good group and 9 (17.6%) in the poor group. In well-pneumatized mastoid, chronic
      inflammatory changes were frequently observed at the lower portion of mastoid
      cells, the round window niche, and the tympanic sinus. In contrast, no such
      incidence of inflammatory change was noted in poorly-pneumatized mastoid. Our
      findings indicate that an intact tympanic membrane does not always mean freedom
      from mastoid inflammation, especially when the mastoid is well-pneumatized. This
      makes it important to check for possible remaining otitis media in patients with
      a well-pneumatized mastoid, even if the tympanic membrane appears normal.

PMID- 14577325
TI  - [Middle ear overpressure treatment in severe Meniere's disease].
AB  - To evaluate the therapeutic effect of middle ear pressure pulse on endolymphatic
      hydrops in humans, Meniett20k was used for 12 months in two severe elderly
      patients with definite Meniere's disease. The average number of vertigo
      occurrences in the 6 months before treatment and in the 12 months after treatment
      started was compared. Numeric values (NV) among patients were calculated and
      categorized into an improved group (NV = 1-40). For hearing function, the pure
      tone average (PTA) before and 12 months after treatment started was compared. PTA
      was calculated based on the following equation: PTA = (A + 2XB + C)/4. A, B, and
      C were thresholds of the pure-tone audiometory at 0.5, 1.0, and 2.0 kHz. In one
      case, hearing function was unchanged, but deteriorated in the other. Pressure
      pulse treatment may thus be useful in severe cases of Meniere's, especially in
      the elderly, bilateral cases, and in endolymphatic hydrops in a single hearing
      ear.

PMID- 14577327
TI  - [Treatment of tonsillitis: evidence based medicine].

PMID- 14577326
TI  - [A case of cervical necrotizing soft tissue infection].
AB  - We treated a 62-year-old woman with a cervical necrotizing soft tissue infection
      of the Streptococcus milleri group. Numerous spot gas images were recognized from
      the right pharynx to the neck in CT at initial diagnosis, but we chose
      conservative treatment because abscess findings were not clear. The inflammation
      improved temporarily, but we operated through an outside incision because
      symptoms recurred and cervical skin became necrotic after one week. Inside, the
      fascia were necrotic and an abscess extended from the precordia to the left upper
      arm and the right axillary region. The cervical skin defect was restored in due
      course in about 2 months and cured without mediastinitis or sepsis developing.
      The S. milleri group was detected in pus. A cervical necrotizing soft tissue
      infection does not form an abscess mainly in one space as does a normal deep neck
      infection and invades fascia space rapidly and widely. We took this disease into
      consideration and had to intervene surgical rather soon. A review of this case
      and the literature indicates that the S. milleri group may have become an
      important pathogen in cervical necrotizing soft tissue infection.

PMID- 14577328
TI  - [Finding of O-mannosyl glycan in mammals and congenital muscular dystrophies due
      to glycosylation defects].
AB  - Most proteins within living organisms contain glycans. Glycan structures can
      modulate the biological properties and function of glycoproteins. Developments in
      glycobiology have revealed a new type of glycosidic linkage to the peptide
      portion, the O-mannosyl linkage in mammals, although heretofore it had been
      thought to be specific to yeast. One of the best known O-mannosyl-modified
      glycoproteins is dystroglycan, which is a central component of
      dystrophinglycoprotein complex isolated from skeletal muscle membranes. We
      identify and characterize a glycosyltransferase, UDP-N-acetylglucosamine: protein
      O-mannose beta 1,2-N-acetylglucosaminyltransferase (POMGnT1), involved in the
      biosynthesis of mammalian type O-mannosyl glycans. Finally, we find that the
      POMGnT1 gene is responsible for muscle-eye-brain disease (MEB). MEB is an
      autosomal recessive disorder characterized by congenital muscular dystrophy,
      ocular abnormalities and brain malformation (type II lissencephaly). Like MEB,
      recent data suggest that the aberrant protein glycosylation of a specific
      glycoprotein, alpha-dystroglycan, is the primary cause of some forms of
      congenital muscular dystrophy. Here I review the new insight into glycobiology of
      muscular dystrophy and neuronal migration disorder.

PMID- 14577329
TI  - [Cooperation of two subtypes of PGE2 receptor, Gi coupled EP3 and Gs coupled EP2
      or EP4 subtype].
AB  - Four prostaglandin E (EP) receptor subtypes have been identified and cloned,
      designated as EP1, EP2, EP3 and EP4. These EP receptors are members of the G
      protein coupled receptor family. EP3 receptor signals are primarily involved in
      inhibition of adenylyl cyclase via Gi activation, while EP2 and EP4 receptor
      signals cause a stimulation of adenylyl cyclase via Gs activation. Immune cells,
      such as mast cells, express multiple EP subtypes on their cell membranes, but few
      studies have been conducted to understand exactly what signals the main flow for
      the multiple subtypes expressing immune cells. We previously demonstrated that
      activation of Gi-coupled EP3 receptor exhibited a cooperative effect on cAMP
      synthesis induced by Gs-coupled EP2 receptor in COS-7 cells. Here we report that
      a selective EP4 agonist-induced adenylyl cyclase activity was augmented by
      simultaneous addition of a selective EP3 agonist in mastocytoma P-815 cells,
      which express mRNAs for both EP3 and EP4 subtypes. The augmentation in cAMP
      synthesis was found to be pertussis toxin-sensitive. P-815 cells are demonstrated
      to bind to Pronectin-F, a proteolytic fragment of fibronectin, in adhesion
      protein of the extracellular matrix, by addition of PGE2, which is mediated by
      PKA. The binding of P-815 cells to Pronectin-F mediated by EP4 receptor was
      augmented by the EP3 receptor. These findings indicate that two subtypes of PGE2
      receptors, EP3 and EP4, cooperatively activate the cAMP-mediated adhesion event
      through induction of fibronectin ligand elicited by PGE2 in P-815 cells.
      Furthermore, the PGE2-induced adhesion response may contribute to the mast cell
      recruitment function on extracellular matrix during inflammation.

PMID- 14577330
TI  - [Involvement of phospholipase A2 in the supply of fatty acids required for
      cholesterol esterification associated with uptake of oxidized low-density
      lipoprotein in macrophages].
AB  - The formation of foam cells, a critical event in the early stages of
      atherosclerosis, is associated with the uptake of oxidized low-density
      lipoprotein (oxLDL) by macrophages and the subsequent accumulation of cholesterol
      ester formed by the catalytic action of acyl-CoA: cholesterol acyltransferase
      (ACAT). Although free cholesterol, a substrate for ACAT, is supplied from the
      intracellular cholesterol pool, little is known about the pathways involved in
      the supply of fatty acids, precursors for fatty acyl-CoA as another substrate for
      ACAT. Our recent studies were undertaken to examine the possible involvement of
      phospholipase A2 (PLA2) in the supply of fatty acids required for the cholesterol
      esterification. In mouse peritoneal macrophages and RAW264.7 macrophages, oxLDL
      induced the liberation of fatty acids from membrane phospholipids to increase
      cholesterol ester having the fatty acids as an acyl chain. The changes in these
      lipids were suppressed by the inhibition of cytosolic PLA2 (cPLA2). Although
      oxLDL did not affect the activity or amounts of cPLA2, preincubation with oxLDL
      enhanced the release of fatty acids induced by Ca2+ ionophore, which accelerates
      the hydrolytic action of cPLA2. We further observed that oxLDL induced the
      generation of ceramide through the de novo synthesis. Exogenous ceramide and 13
      hydroxyoctadecadienoic acid, an oxidized lipid in oxLDL particles, also
      stimulated fatty acid release. Based on these findings, we propose that oxLDL
      activates cPLA2 to supply fatty acids required for the cholesterol
      esterification, through the acceleration of the hydrolytic action of cPLA2 by
      endogenous ceramide and by oxidized lipids in oxLDL particles in macrophages.

PMID- 14577331
TI  - [Free radicals mediate cardiac toxicity induced by adriamycin].
AB  - Anthracycline antibiotics, including adriamycin (ADM), are widely used to treat
      various human cancers, but their clinical use has been limited because of their
      cardiotoxicity. ADM is especially toxic to heart tissue. The mechanisms
      responsible for the cardiotoxic effect of ADM have been very/extremely
      controversial. This review focuses on the participation of free radicals
      generated by ADM in the cardiotoxic effect. ADM is reduced to a semiquinone
      radical species by microsomal NADPH-P450 reductase and mitochondrial NADH
      dehydrogenase. In the presence of oxygen, the reductive semiquinone radical
      species produces superoxide and hydroxyl radicals. Generally, lipid peroxidation
      proceeds by mediating the redox of iron. ADM extracts iron from ferritin to form
      ADM-Fe3+, which causes lipid peroxidation of membranes. These events may lead to
      disturbance of the membrane structure and dysfunction of mitochondria. However,
      superoxide dismutase and hydroxyl radical scavengers have little effect on lipid
      peroxidation induced by ADM-Fe3+. Alternatively, ADM is oxidatively activated by
      peroxidases to convert to an oxidative semiquinone radical, which participates in
      inactivation of mitochondrial enzymes or including succinate dehydrogenase and
      creatine kinase. Here, we discuss the activation of ADM and the role of reductive
      and oxidative ADM semiquinone radicals in the cardiotoxic effect of this
      antibiotic.

PMID- 14577332
TI  - Preliminary pharmacological study of purified snake enzymatic cream isolated from
      Agkistrodon Halys venom.
AB  - To investigate the pharmacological and toxicological actions of purified snake
      enzymatic cream (PSE) isolated from Agkistrodon Halys Venom, erythematous
      dermatitis was induced by applying dinitrofluorobenezene (DNFB) on the back skin
      of guinea pigs. Consequent local alterations at different doses of PSE were
      observed and compared using negative control methods. In skin irritation and
      acute toxicological experiments, 500 times the effective doses were used in
      artificially lesioned skin. The marking criteria in the former were based on
      local manifestations, and in the latter, on changes of some indicators including
      body weight, breath, and heart rate before and after the experiments. PSE
      significantly alleviated erythematous dermatitis (p < 0.01, t test) without
      systemic or local adverse drug reactions within 7 days. PSE as a new drug
      candidate poses a bright prospect in the prevention and treatment of dermatitis.

PMID- 14577333
TI  - [Biological activities of Salacia chinensis originating in Thailand: the quality
      evaluation guided by alpha-glucosidase inhibitory activity].
AB  - In the course of our characterization studies on anti-obese and antidiabetogenic
      principles in medicinal foodstuffs, we found that the methanolic extract from the
      stems of Salacia chinensis (Hippocerateaceae) showed potent anti-hyperglycemic
      effects in oral sucrose or maltose-loaded rats, inhibitory effects on intestinal
      alpha-glucosidase, rat lens aldose reductase, formation of Amadori compounds and
      advanced glycation end-products, nitric oxide production from lipopolysaccharide
      activated mouse peritoneal macrophage, and radical scavenging activities. Those
      in vivo and in vitro biological activities were compared with those of S. oblonga
      and S. reticulata. In addition, we isolated the principal alpha-glucosidase
      inhibitor, salacinol, from the stems of S. chinensis and examined alpha
      glucosidase inhibitory activities of eleven samples of S. chinensis collected in
      Thailand.

PMID- 14577335
TI  - [Investigation of the reconsultation rate and pharmacoeconomic evaluation of
      period of influenza treatment by oseltamivir].
AB  - In the epidemic of influenza in fiscal 2002, there was a shortage in Japan of the
      anti-influenza virus medicine "oseltamivir". For this reason, many medical
      institutions were forced to shorten the treatment period with this medication. In
      this study, we compared the shorter oseltamivir treatment and the indicated 5-day
      course of treatment with the index for the reconsultation rate and medication
      dispensing fee from the viewpoint of pharmacoeconomics and clinical effect.
      Oseltamivir was prescribed for 2, 3 or 5 days for the treatment of influenza, and
      the rate of reconsultation, type of virus and age were analyzed. The total fees
      paid to a pharmacy for influenza treatment were also calculated for
      pharmacoeconomic evaluation. Two-day treated patients had a higher rate of
      reconsultation compared with the 3- and 5-day treatment groups. Analysis of
      patients by influenza virus type and age showed no significant difference in
      reconsultation rate. The total medication dispensing fees for 2-, 3- and 5-day
      treatment with oseltamivir were 4713, 4755 and 6520 yen, respectively, that of 5
      day treatment being significantly higher. These results suggest that 2-day
      treatment by oseltamivir was significantly high in reconsultation rate, and 5-day
      treatment was significantly high in medication dispensing fee, so 3-day treatment
      of influenza by this medicine is the most suitable from the viewpoint of
      pharmacoeconomics and clinical effect.

PMID- 14577334
TI  - Establishing a comprehensive questionnaire for detecting drug-induced
      extrapyramidal symptoms.
AB  - OBJECTIVE: Drug-induced extrapyramidal symptoms (DIEPS) often substantially
      compromise quality of life (QOL) of patients receiving drugs with central
      antidopaminergic activities. A lack of comprehensive screening method based upon
      patients' subjective symptoms for detecting DIEPS appears to have prevented
      pharmacists from delivering satisfactory pharmaceutical care for these patients.
      Thus, we have attempted to develop a comprehensive questionnaire for screening
      patients having higher risks of developing DIEPS. METHODS: One hundred fourteen
      outpatients taking gastroprokinetic drugs (itopride, cisapride, trimebutine,
      domperidone and metoclopramide) at least 2 weeks participated in the study. One
      patient with familial Parkinson disease served as a positive reference. They
      undertook a questionnaire consisting of 9 comprehensive questions written in non
      technical words that were aimed to detect typical symptoms of Parkinsonism
      including akathisia and dyskinesia. Each symptom was scored in a semiquantitative
      scale [i.e., from 1 (not at all) to 5 (very much)] by the patients. RESULTS: Of
      the 108 subjects who successfully completed the questionnaires, 43 gave scores 2
      or greater indicating the presence of DIEPS. However, no statistically
      significant correlations were observed between the scores of any possible pairs
      of the questionnaire items. Five subjects had a mean questionnaire score of equal
      to or greater than 1.6, and the patient with familiar Parkinsonism had the
      highest mean score of 1.9. CONCLUSION: The questionnaire presented herein
      detected 4 patients with suspected DIEPS. Further studies should be warranted to
      assess whether it would be useful for pharmacists as a screening tool for DIEPS
      in patients having higher risks of DIEPS.

PMID- 14577336
TI  - [Establishment and effect of the drug safety management monitoring system].
AB  - Early detection and early treatment of adverse drug reactions have recently
      become more important. It is natural that physicians should treat adverse drug
      reactions carefully, but it is also important to establish a system for their
      early systematic detection and treatment. Therefore, by comparing current data
      with that preserved in our clinical laboratory's data management registry and
      identifying values significantly different from earlier values, we established a
      screening system for any condition which may have a possible relationship with
      drugs and feeds back the results to the physician(s) in charge (drug safety
      management monitoring system). The effectiveness of the system was then
      evaluated. The subjects were outpatients who visited the Diabetes Endocrine
      Metabolism Center of our hospital during a six-month period. Cases where the
      possibility of a relationship between abnormal changes of laboratory data and
      drugs was not ruled out were reported to the attending physician using a drug
      safety monitoring report form. In 14 of 34 cases reported, a relationship with
      drugs could not be ruled out. Two of these 14 cases were reported to the Ministry
      of Health, Labour and Welfare because they were serious. Therefore, it was
      concluded that this system was useful for early detection of adverse reactions.

PMID- 14577337
TI  - [Biomechanics and biomaterials--dental instruments, prosthesis and bone
      regeneration].

PMID- 14577338
TI  - [Factors determining radioresistance of tumors].

PMID- 14577339
TI  - [Patients' survey on regular check-up system in dental clinics].
AB  - This survey classified the issues involved in promoting the regular check-up
      system in dental clinics. The survey was conducted in two parts: interviews with
      39 dental clinics and a questionnaire survey of 5,129 patients (response rate:
      56.8%). The results are summarized as follows: 1. Among the dental clinics that
      participated in this survey, the proportion of regular patients, the number of
      dental hygienists working at clinics, and the number of patients per day were
      higher than those of the national average. 2. The demographic patterns of
      regularly attending patients were "female, aged under 14 years and students or
      public servants". 3. Satisfaction with the technical competence of hygienists has
      the strongest correlation with regularity of visiting. The degree of correlation
      was about twice that of the correlation with technical competence of the dentist.
      4. Patients' priorities for improving dental services to enhance satisfaction
      were treatment charges, appointment system, and attitude of staff and doctors
      toward welcoming the patients.

PMID- 14577340
TI  - [Fit of electroformed porcelain-fused-to-metal crown on implant abutment].
AB  - This study compared the adaptation of a conventional and an electroformed
      porcelain-fused-to-metal crown. A master model was selected from an ITI implant
      with a solid abutment (height: 4 mm). Conventional cast metal frameworks of 0.7
      mm thickness were prepared with a high noble metal alloy (Degudent U, Degussa)
      for porcelain fusing (n = 5). Electroformed frameworks of 0.2 mm thickness were
      determined using pure gold deposition on the abutment using the Auro-Galva-Crown
      system (AGC, Wieland) (n = 5). Subsequently, a porcelain (Super Porcelain AAA,
      Noritake) was fused to each framework. Internal gaps between the framework and
      its abutment were determined using the thickness of a silicone fit checking
      material. The gaps were measured both before and after porcelain fusing. The
      thicknesses of the silicone layer of the electroformed and the conventional
      porcelain-fused-to-metal crown were 34.6 and 38.5 microns at the margin, 33.2 and
      39.6 microns at the internal slope, 22.0 and 33.0 microns at the axial, 58.6 and
      65.1 microns at the occlusal, respectively. Three-way analysis of variance
      revealed that the mean gaps in the electroformed porcelain-fused-to-metal crown
      were significantly thinner than those in the conventional porcelain-fused-to
      metal crown (p < 0.05). The electroformed porcelain-fused-to-metal crown showed
      better adaptability than the conventional porcelain-fused-to-metal crown
      regardless of porcelain fusing.

PMID- 14577341
TI  - [A clinical study on unfavorable cases of dental implant].
AB  - The clinical analysis of 462 patients (154 men and 308 women) with problems of
      implant therapy done at other clinics is reported. They visited the clinic for
      oral implant of the Tokyo Medical and Dental University Hospital during the
      period from January 1996 to March 2002. The results were as follows: 1) The
      majority of the patients (76.6%) were 40 to 69 years of age. 2) Of the total
      patients, 26.8% had been referred from the other outpatient clinics in our
      hospital, 14.7% from private dental offices and 2.6% from attending doctors. 3)
      There were 361 patients with complications related to the implant therapy.
      Seventy-six patients asked for second opinions concerned about a diagnosis or
      treatment recommendation. Thirty patients required maintenance of the implants.
      4) The most common complications observed were peri-implantitis (184 cases).
      Prosthodontic complications (72 cases) included framework/resin/veneering
      material fractures, screw loosening and fractures. There were implant fractures
      in 21 cases, sensory disturbance in 20 cases, problems related to sinus in 13
      cases, problems of connected teeth in 30 cases and phonetic/esthetic
      complications in 10 cases. 5) The types of problem implants were osseointegrated
      implants (196 cases), alumina-ceramic implants (74 cases), metallic blade-type
      implants (35 cases), pin-type implants (10 cases), subperiosteal implants (6
      cases) and other implants.

PMID- 14577342
TI  - [Postoperative evaluation of surgically treated cases with temporary silicone
      implant in temporomandibular joint].
AB  - We have carried out temporary silicone implants after diskectomies or
      arthroplasties in temporomandibular joint surgeries to avoid postoperative
      adhesion and to maintain articular space. We evaluated 19 joints in 15 patients
      who had received dacron-reinforced silicone implant after silicone sheet removal
      through follow-up for at least 6 months. The cases included temporomandibular
      joint disorder (10 joints in 9 patients), psoriatic arthritis (2 joints in 1
      patient), ankylosis (4 joints in 3 patients) and synovial chondromatosis (2
      joints in 2 patients). On the basis of the criteria of temporomandibular
      dysfunction for the results, they were classified as bad (4 patients). It is
      thought that factors other than the implant are related to the bad results in the
      postoperative evaluation. In this study, lymphadenopathy induced by exfoliated
      silicone debris could not be confirmed. The temporary silicone implant in the
      temporomandibular joint was thought to be useful.

PMID- 14577343
TI  - [The importance of the examination of, education on, and infection control of
      tuberculosis in medical school hospitals in Japan].
AB  - Since the incidence of tuberculosis (TB) has markedly decreased over the last
      half-century, dedicated TB hospitals in Japan have been reducing the beds or have
      been merging with other hospitals. In accordance with this situation, less than
      30% of medical school hospitals (MSHs) have facilities for infectious TB
      patients. In the meantime, and contrary to the previous trend, elderly TB
      patients or those who have serious underlying diseases have been increasing. MSHs
      have therefore not only to take care of these patients, but at the same time they
      have to reform their TB education system in addition to upgrading TB infection
      control. To elucidate the current problem regarding TB in MSHs, the survey in the
      current study was performed for 80 MSHs in Japan in January 2002. Two sets of
      questionnaires were prepared and delivered to doctors in these hospitals. One set
      mainly asked about the status of TB examination and education, and was aimed at
      doctors in the division of respiratory diseases of the department of internal
      medicine (Rs); and the other mainly asked about the status of TB infection
      control and was aimed at doctors in the divisions of infectious diseases, or
      whoever in charge of hospital infection control (Is). Response rates from Rs and
      Is were 75.0% (60/80) and 65.0% (52/80), respectively. Seventy-three point three
      percent (44/60) of Rs and 73.1% (38/52) of Is were working in hospitals without
      TB beds. Because of the current incidence of TB, the number of TB patients they
      examined in a year was small (35/60 of hospitals examined less than 20 TB
      patients in a year). Although there were some experienced doctors on TB in each
      hospital, most MSHs had only a small number of experienced nurses. Nevertheless,
      89.3% of doctors in MSHs (a total of 100/112 Rs and Is) believed that they
      required TB rooms exclusively for TB patients who have some underlying diseases,
      and for TB education. Regarding the role of MSHs for TB patients care, the
      majority of doctors (70.5% of Rs and 68.4% of Is) considered MSHs should be able
      to offer treatment to TB patients with underlying complications. As to the
      educational aspect, most medical schools (MSs) devoted little time to lectures on
      TB (the median was 1 to 1.5 hour); on the other hand, some MSs (31.8%: 14/44 of
      MSHs without TB rooms) included a clinical practices in TB hospitals for TB
      education, although its term was short. Regarding TB infection control issues,
      most of the MSHs had active infection control committees in their hospitals and
      TB was thought to be one of the most important targets for these committees.
      About 40% (20/51) of these hospitals over the past few years had experienced
      nosocomial TB infection due in part to the so called "Doctor's delay". As one of
      the strategies to prevent nosocomial TB infection, special education sessions,
      not only for staff and residents but also students, were therefore performed in
      60.8% (31/51) of MSHs. As to the evaluation of the tuberculin skin test (TST)
      status of medical students, the two-step TST was performed in 47.1% (24/51) of
      MSs (as most Japanese underwent their BCG vaccination in their childhood) and
      54.9% (28/51) of MSs had a BCG revaccination policy for TST negative students.
      Although steps toward reforms in TB issues in MSHs were slow, some minor progress
      had been made as compared with previous surveys performed by us and others. Even
      though the numbers of TB patients examined in MSHs have been smaller than before,
      MHSs still have to take care of some TB patients with some complications. A great
      deal of effort still needs to be expended to establish efficient and effective TB
      education and infection control systems. Even though many ideas have been put
      forward to improve the current situation, one of the most successful answers is
      to set up small number of special rooms, not only for TB patients but also for
      other airborne infectious diseases, in all MHSs. The other clue is to establish
      an intimate collaboration between MSHs and TB hospitals with regard to clinical
      TB education not only for medical students but also for medical staff.

PMID- 14577344
TI  - [Usefulness of directly observed therapy (DOT) during hospitalization as DOTS in
      Japanese style].
AB  - Many patients with smear positive tuberculosis were hospitalized during the
      initial phase of chemotherapy but DOT was not applied to patients with
      tuberculosis in Japan. We tried randomized clinical study to evaluate the
      usefulness of DOT during admission. 135 culture positive TB patients were
      administered by DOT and 124 culture positive TB patients were self-administered
      during admission. There was no significant difference between 2 groups in the
      clinical background factors, treatment and the incidence of adverse reactions.
      Treatment completion rate was 94.1% in DOT group and 87.9% in non-DOT group.
      Default rate was significantly lower in DOT group (4.4%) than in non-DOT group
      (11.3%). We concluded that "DOT during admission" was useful to improve the
      outcome of chemotherapy for tuberculosis and it is preferable to apply DOT
      throughout treatment course for patients with tuberculosis in Japan.

PMID- 14577345
TI  - [Activity of cephems and carbapenems against clinically isolated Mycobacterium
      abscessus].
AB  - To screen effective useful drugs for disease due to M. abscessus, we determined
      MIC of 3 cephems [ceftazidime (CAZ), cefoxitin (CFX), flomoxef (FMOX)] and 3
      carbapenems [imipenem (IPM), panipenem (PAPM), meropenem (MEPM)] for 8 strains of
      clinically isolated M. abscessus by micro-dilution method using MGIT system. In
      all the 8 strains, MICs of CAZ are higher than 32 micrograms/ml. MIC50, MIC90,
      MIC range of CFX are 32 micrograms/ml, > 32 micrograms/ml and 16- > 32
      micrograms/ml respectively, and for FMOX, 16 micrograms/ml, 32 micrograms/ml and
      16-32 micrograms/ml; for IPM, 8 micrograms/ml, 16 micrograms/ml and 8-16
      micrograms/ml; for PAPM, 4 micrograms/ml, 16 micrograms/ml and 4-16
      micrograms/ml; for MEPM, 8 micrograms/ml, 16 micrograms/ml and 8-16
      micrograms/ml. From this study, it is concluded that FMOX, IPM, PAPM and MEPM can
      be clinically useful drugs in the treatment of the disease due to M. abscessus.

PMID- 14577346
TI  - [Pulmonary Mycobacterium kansasii infection in Okayama, Japan].
AB  - Our group discovered the first patient with pulmonary M. kansasii infection in
      Okayama Prefecture in 1976. The first case and another ten more patients over
      about eight years came exclusively from the southern seaside area of Kurashiki
      City (Mizushima Marine Industrial District and its vicinity). Thereafter, the
      cases of pulmonary M. kansasii infection have spread geographically and
      chronologically from the Mizushima district to neighboring areas in the
      prefecture. We considered the possibility of human-to-human transmission of M.
      kansasii by both the observed geographic spread and the existence of at least two
      occupational clusters (three welders working on the same line in the same factory
      building and nine workers in one ironworks), but we could not resolve several
      controversial problems.

PMID- 14577347
TI  - [Development of new therapeutic method for empyema].
AB  - OBJECTIVES: We have investigated whether polylactic acid (PLA) sponge and
      fibroblast-growth-factor (FGF) released slowly from gelatin beads can induce
      fibrotic tissue in postpneumonectomy dead space. METHODS: Left pneumonectomy was
      performed in white Japanese rabbits. In the control group (N = 5), left chest was
      closed without any treatment. In the PLA sponge group (N = 5), PLA sponge and FGF
      (100 micrograms) released from gelatin beads were introduced into the left chest
      cavity. RESULTS: In the control group, herniation of the heart and right lung
      were observed without fibrotic material in the left chest cavity. In the PLA
      sponge group, dense fibrotic material was observed by chest CT scan 1 month after
      the operation. Pathological examinations revealed that PLA sponge and FGF did
      promote the organization of the fibrotic materials. CONCLUSIONS: Fibrotic
      materials can be induced in the postpneumonectomy dead space by PLA sponge and
      FGF released slowly from a gelatin sponge. New therapeutic method may be
      introduced near future by this concept, reduction of dead space with newly
      developed own fibrotic materials.

PMID- 14577348
TI  - [Role of new quinolones in the treatment of mycobacteriosis].
AB  - New quinolones (NQs) have acquired potent antimicrobial activity against gram
      positive cocci and penetrate well into organs when compared with old quinolones.
      Their indications were extended to the treatment of respiratory infection caused
      by gram-negative and gram-positive bacteria, and their possibility of an
      indication for the treatment of mycobacteriosis has been considered.
      Mycobacteriosis, against which NQs are expected to be effective, includes
      tuberculosis, which involves a problem of multiple-drug resistant bacteria, and
      atypical mycobacteriosis, for which there are few remedies. Since, there has been
      no established evaluation of NQs against mycobacteriosis, the purpose of the
      present evening symposium was to evaluate the role of NQs at present in the
      treatment of mycobacteriosis, as well as to present future prospects. Four
      speakers made presentations. Dr. Chiaki Sano reported that STFX, GFLX, MXFX, and
      SPFX had a potent antibacterial activity against various acid-fast bacteria and
      were particularly effective against M. tuberculosis, M. kansasii, and M.
      fortuitum. Among these drugs, MXFX had a greater therapeutic effect in
      experimental mice model of a tuberculosis than SM when used concomitantly with
      INH + RPT. These results suggested that MXFX might become one of the first-line
      drugs, taking the place of SM. However, OFLX, SPFX, and STFX are not effective
      against MAC. Only MXFX exhibited a significant therapeutic effect when
      administered alone and potent therapeutic effect when used concomitantly with EB,
      in experimental mice model of MAC infection. These results suggested that 8
      methoxy quinolone might be effective. Dr. Yuka Sasaki reported the results of a
      questionnaire survey among national sanatoriums, as well as the current status of
      administration of NQs for the treatment of pulmonary tuberculosis based on the
      results of her study. The ATS recommended in 2002 that LVFX, MXFX, and GFLX be
      second-line drugs, which should be used alternatively only when first-line drugs
      cannot be used due to drug-resistant M. tuberculosis or adverse reactions. She
      reported that LVFX, MXFX, and GFLX were used in a similar manner also in Japan
      and that they achieved therapeutic results equivalent to those by first-line
      drugs. She stated that there were some urgent problems, for example, these drugs
      are not listed in the Tuberculosis Control Law of Japan or in health insurance,
      and no testing system for sensitivity to NQs has been established. Dr. Atsuyuki
      Kurashima reported the results of a study conducted in other countries and his
      study on atypical acid-fast bacteria. He indicated the position of NQs in the
      treatment of pulmonary atypical mycobacteriosis. However, the significance of
      concomitant use of CPFX with RFP + EB in the treatment of MAC disease associated
      with AIDS has already been recognized. He was of the opinion that atypical acid
      fast bacteria against which NQs were useful were M. kansasii and M. fortuitum
      alone at present and that NQs had a very limited effect in the treatment of
      pulmonary MAC infection, although there were only an insufficient number of
      studies on pulmonary MAC disease. Dr. Koichi Wada reported on the advisability of
      administration of NQs in the treatment of mycobacteriosis as a whole and
      prospects for NQs. His conclusion was similar to those by the two former
      speakers: he stated that NQs are important for the treatment of tuberculosis as
      alternative drugs and that they should be used in sufficient doses when first
      line drugs could not be used due to drug resistance or adverse reactions. He also
      stated that use of NQs, including duration of administration, should be discussed
      after the testing method for drug sensitivity has been established and that long
      term use of NQs should be avoided in the treatment of atypical mycobacteriosis at
      present, although significant results have not been obtained in atypical acid
      fast bacteria, mainly MAC. In the last part of the symposium, an active
      discussion was held. Many opinions similar to those of the speakers were
      expressed also from the floor. Lastly, President Dr. Matsushima summarized the
      role of NQs in the treatment of mycobacteriosis at present and future prospects
      for NQs and confirmed the significance of having held the present symposium.

PMID- 14577350
TI  - [Regulation of NO production and NO-mediated apoptosis].

PMID- 14577349
TI  - [Small Maf proteins as transcription factors regulating maturation and
      maintenance of the cell].

PMID- 14577351
TI  - [Structure and function of Ca2+ pump and diseases caused by its gene mutations].

PMID- 14577352
TI  - [Identification and characterization of aminopeptidases belonging to the
      oxytocinase subfamily].

PMID- 14577353
TI  - [AGE-RAGE system in the development of diabetic vascular complications].

PMID- 14577354
TI  - [The development of vitamin D analogs as a therapeutic agent].

PMID- 14577355
TI  - [Relationship between phagocyte functions and regulation of actin cytoskeleton by
      LIM-kinase and cofilin].

PMID- 14577356
TI  - [Disturbance of intracellular signaling by Helicobacter pylori infection].

PMID- 14577358
TI  - [Photo-mediated gene activation/inactivation by novel caging agent].

PMID- 14577359
TI  - [Diagnostic conization of the uterine cervix and its effect on survival of
      patients after Wertheim-Meigs hysterectomy].
AB  - The aim of this retrospective work was to evaluate the diagnostic conization and
      its influence on morbidity and survival of patients with cervical cancer IB and
      IIA stage after radical hysterectomy a modo Wertheim-Meigs. The impact and
      influence of the irradical conization on the lymph node metastases and prognosis
      was analyzed. 535 patients in stage IB and IIA were examined for the period of
      1990 and 2002. All of them were radically operated by Wertheim-Meigs method.
      There were 35 patients mainly from the countryside, who were treated by
      conization priory to radical hysterectomy. The time interval between the
      conization and the radical hysterectomies was between 5 and 8 weeks. The surgical
      morbidity and death incidence for patients with prior conization was not
      significantly different from other patients with directly radical hysterectomies.
      The survival was not significantly different between the two groups (84% vs 81%,
      p = 0.21). The Multivariate analysis which we used showed us that the irradical
      conization is not connected with higher risk of metastases or poor prognosis. We
      think that in early cervical cancer, the diagnostic conization has no adverse
      negative effect on the following radical hysterectomy a modo Werheim-Meigs. The
      irradical conization has no influence on prognosis.

PMID- 14577357
TI  - [Expression of SSEA-1 in the developing brain].

PMID- 14577360
TI  - [Antibiotic prophylaxis in limited gynecological surgeries for pregnancy
      termination].
AB  - The authors attempted with this trial to confirm the necessity of periabortal
      antibiotic prophylaxis after spontaneous and induced abortion. The trial included
      172 patients with abortion; 53 of them with induced abortion and 119 with
      spontaneous abortion. The term of gestation was between 5 and 22 week. Three
      therapeutic groups were compared to a control no-treatment group. The first group
      was given Ampicillin orally 4 x 500 mg for 5 consecutive days. The second group
      was administered a combination of Ampicillin orally 4 x 500 mg plus Gentamycin 2
      x 80 mg i.m. for 3 to 5 days postoperatively. The third group was given 3 x 2 g
      i.v. Cefazolin intraoperatively and 24 hours following the manipulation. The
      trial aimed at establishing the efficiency and cost-effectiveness of the
      antibiotic prophylaxis. The results tend to prove the perioperative prophylaxis
      with Cefazolin is preferable since it is most efficient and cost-effective.

PMID- 14577361
TI  - [Comparative diagnostic characteristics of carbohydrate metabolism disorders in
      women with polycystic ovary syndrome (PCOS)].
AB  - The aim of the study was to compare the information provided by both fasting and
      stimulated during a standard oral glucose tolerance test (oGTT) levels of glucose
      and insulin as regards glucose tolerance and insulin resistance in women with
      PCOS. Few criteria are used in practice to verify insulin resistance in PCOS-
      elevated fasting insulin, decreased basal glucose/insulin ratio (< 6 for glucose
      in mg/dl or < 0.333 for glucose in mmol/l), insulin increase of more than 100 lul
      during an oGTT, and HOMA index > 2. The study comprised of 94 women (mean age
      21.8 +/- 5 = 8 ys, mean BMI-30.38 +/- 7 = 7 kg/m2), divided in 4 groups according
      to BMI--group with BMI < 25, n = 21; group with BMI25-30, n = 27; group with BMI
      = 30-35, n = 23 and group with BMI > 35, n = 23. An oGTT with parallel
      determination of blood glucose and insulin was performed in all patients. The
      ratio basal glucose/insulin and HOMA index were calculated. Glucose levels on the
      2 md hour during the oGTT pointed at IGT (impaired glucose tolerance) and/or
      diabetes in 8.5% of the investigated patients while the fasting levels indicated
      disturbances in only 2.2% of them. Fasting insulin levels were in the normal
      range in a considerable part of PCOSE women, mainly those with normal weight, and
      were not predictive for the response of insulin to glucose load. Relative percent
      of patients with elevated fasting insulin rose with the increasing of BMI.
      Decreased glucose/insulin ratio, elevated HOMA index, and abnormal stimulation of
      insulin were seen in more than 2/3 of the PCOS women including nonobese ones.
      Information provided by the above three markers was similar and they could be
      used alternatively according to the particular case and assessment of the
      cost/benefit ratio.

PMID- 14577362
TI  - [Clinical study of the low dose oral contraceptive novynette].
AB  - The authors review the efficacy, control of the menstrual cycle and the tolerance
      of the low-dosed oral contraceptive Novynette (20 mkg EE/150 desogestrel) of
      Gedeon Richter at 25 women, included in the study. The results show: Pearl index
      = 0.00, a good control over the menstrual cycle, not significant and transitor
      side effects.

PMID- 14577363
TI  - [Is the directed biopsy accurate?].
AB  - The aim of the present study was to evaluate the diagnostic accuracy of the
      colposcopically directed biopsy of cytologically signalized women.
      Retrospectively were analyzed sixty women aged between 20 and 69 (mean 37.4), to
      whom was performed colposcopically directed biopsy and consequent in the interval
      of no more than 3 months extended excision (to 30 of them--surgical conisation
      and to another 30--LLETZ/LEEP). Summarized data shows, that in 47 (78.3%) of them
      there are coincidence to one degree difference in the histological findings, and
      of the remain 13 cases--in 4 (6.7%) there are false positive results, and in 9
      (15.0%)--false negative. The value of the sensitivity is 83% and of the
      predictive value of the positive results is 91.7%, which put them in the borders
      of the good performance of the diagnostic test. The conclusion is that the
      accuracy of the directed biopsy is determined by the presence or absence of the
      good correlation between cytological, colposcopical and histological
      investigation, as the implementation of the excisional biopsies enlarged the
      possibilities of the diagnostic protocol for the following adequate therapeutic
      action.

PMID- 14577364
TI  - [Autohemotransfusion].
AB  - The new tendency in used transfusion practice in surgery treat the problem of
      blood loss and its supplementation with minimal transfusion risk. Transmissive
      infections and immune complication after blood transfusion are still actual
      today. The autotransfusion is reasonal alternative in modern transfusion therapy.

PMID- 14577365
TI  - [Induction of labor--current concepts].

PMID- 14577366
TI  - [Diagnostic and clinical status of premature ovarian failure].
AB  - Premature Ovarian Failure is a heterogeneous disorder with numerous causes. The
      exact prevalence of POF is unknown. In this study, we want to make Differentiate
      diagnosis of hypergonadotropic amenorrhea and to determine the difference between
      them. Retrospective, we follow up 475 women at which we perform ovarian
      stimulation and we observe that 6 (1.3%) have Gonadotropin resistant ovary
      syndrome in IVF-centre--MU--Varna.

PMID- 14577367
TI  - [Estrogen replacement therapy with oestrogel].
AB  - The author makes an overview of the characteristics of the ERT (estrogen
      replacement therapy) with Oestrogel (Laboratoires Besins-International). The
      latter is a hydro-alcoholic gel, containing 0.06% 17 beta estradiol for
      transdermal application. The specific characteristics of this type of estrogene
      replacement are discussed as well as some of its advantages over the rest
      products.

PMID- 14577368
TI  - [Efficacy of duphaston treatment in women with endometriosis after reconstructive
      surgery].
AB  - The authors present outcomes of inspection of 300 women suffering from genital
      endometriosis. Localization and thermocoagulation of endometriosis was performed
      by diagnostic and operative laparoscopy. After operation women were treated with
      hormonomodulative therapy. Patients were divided in five groups, depending on
      prescribed treatment. The authors concluded that the most effective is therapy
      with progestine dydrogesterone (Duphaston). For comparison there are presented
      groups of patients without hormonal treatment after operation. The authors
      recommend hormonomodulative therapy after surgical treatment of endometriosis.
      Duphaston was indicated as the most preferable drug.

PMID- 14577369
TI  - Expressions of human p53 and c-myc gene homologues during caryopsis development
      in maize.
AB  - Tumor suppressor gene p53 and proto-oncogene c-myc have been proved to be highly
      conserved and participate in many PCD processes in animals. In maize, proteins
      and RNAs related to p53 and c-myc have already been reported and the sequences
      homologous to these two genes have also been localized onto maize chromosomes by
      FISH. In this study, using immunohistochemistry we investigated the expression
      patterns of maize genes homologous to human p53 and c-myc during caryopsis
      development stages in maize. In a giving stage after pollination, p53 homologue
      showed high levels in the antipodal cells, integument, immature endosperm, ovary
      wall, tracheary elements, and aleurone layer, while c-myc homologue showed low
      levels in these tissues, only before pollination showed high expression in polar
      nucleus. The results of TUNEL assay demonstrated that TUNEL positive signals were
      detected where p53 homologue showed high expression levels. In animal cells, p53
      shows reverse function with that of c-myc, so does it in maize basically. These
      results demonstrated that p53 and c-myc homologues might play some important
      roles in PCD during caryopsis development in maize. There may be conserved
      mechanisms for PCD in animals and in high plants.

PMID- 14577370
TI  - [Analysis of photoperiod-sensitivity genes in Minghui63, an restorer line of
      indica rice(Oryza sativa L.)].
AB  - Hybrid rice is very important in agriculture production in China. Its selecting
      property makes it significant to study the genetic performance of F1's date to
      heading (DH). Minghui63, an indica rice restorer line, has been widdly applied to
      hybrid rice seed production in China, but the photoperiod-sensitivity gene of
      heading date in this restorer line is still unknown. This definitely limited the
      further use of this restorer line in breeding practice and re-production of
      hybrid seeds. To solve this problem, using heading time nearly isogenic lines EGO
      EG7, ER-LR and two heading date QTL-isogenic lines, NIL (Hd1) and NIL (Hd4), with
      the genes of Nipponbare but Hd1 (Se-1) and Hd4 (E1) genes from Kasalath,
      respectively, we performed a genetic analysis of Minghui63 with special reference
      to photoperiod-sensitivity loci, using natural long days in Nanjing(32 degrees N)
      and natural short days in Linshui county, Hainan province (18 degrees 29'N),
      where the average day-length is about 14 h and 11.6 h during the course of rice
      growing, respectively. The F1 and F2 generations from the crosses "heading time
      nearly isogenic lines x Minghui63" were subjected to genetic analyses.
      Experimental results showed that Minghui63 carries photoperiod-sensitivity allele
      gene E1 and E3 in E1 and E3 loci, respectly, and a photoperiod insensitivity
      allele Se-1e in Se-1 locus, and it also carries a recessive inhibitor for
      photoperiod-sensitivity gene E1. Meanwhile, the photoperiod-sensitive genes, E1
      and the photoperiod-insensitive genes, Se-1e, in Minghui63 were also identified
      by crossing with the nearly isogenic lines for heading time QTLs, NIL (Hd1) and
      NIL(Hd4). The results indicated that Minghui63's genotype of heading date was:
      E1E1e2e2E3E3Se-1eSe-1e. The result from this research indicated that Minghui63
      carries a major dominant photoperiod-sensitive gene E1 in E1 locus, and our
      previous researches indicated that Zhenshan97A carried a major dominant
      photoperiod-sensitive gene Se-1n in Se-1 locus and a recessive inhibitor gene i
      Se-1. The DH of the hybrid rice "Shanyou63" is 94.7 in Nanjing, lying between
      Zhenshan97A's and Minghui63's, but more nearer to late maturity parent Minghui63.
      It has been not expressed that E1 gene usually prolongs days to heading by about
      20 days when coexisting with Se-1u or Se-1n. This is possibly made by that
      inhibitor genes exist in respective parents, which make DH transgression of
      "Shanyou63" not appear. This phenomenon indicated that the heading date of indica
      hybrid rice is resulted from the interaction among the photoperiod-sensitive
      genes and their inhibitor genes in the sterile and the restorer lines.

PMID- 14577371
TI  - [Towards the positional cloning of a spikelet identity gene frizzle panicle (FZP)
      in rice (Oryza sativa L.)].
AB  - FZP is a key gene for spikelet differentiation in rice. Mutation of the gene
      blocks the differentiation of spikelets and makes rachis branches develop
      unlimitedly. A mutant of the gene named frizzle panicle (fzp) was previously
      found from the high-generation progeny of a cross between two Oryza sativa ssp.
      indica rice varieties, V20B and Hua1B. With the mutant, FZP had been mapped to a
      chromosomal region of about 26.4 cM in width between two SSR (Simple Sequence
      Repeat) markers, RM172 and RM18, on chromosome 7. In this study, high-resolution
      mapping of the gene was carried out for the positional cloning of the gene. Two
      flanking SSR markers, NRM6 and NRM8, were identified, which are 0.2 cM and 1.0 cM
      apart from the target gene, respectively, bracketing the target gene within an
      interval of 1.2 cM or 144 kb. An APETALA2 (AP2)-domain like gene was found at the
      expected position of FZP. As AP2 is known to play an important role in the floral
      development, we took it as the most possible candidate of FZP. PCR analysis
      showed that the mutant allele of the AP2-domain like gene contains an insert of
      about 4 kb in length, suggesting that the gene is very likely FZP.

PMID- 14577372
TI  - [Genetic analysis about maize male sterile mutant obtained by space flight].
AB  - The seeds of maize single hybrid Chuandan No. 9 were carried into space in 1996
      by satellite. After the seeds were planted in field in comparison with travel in
      space seeds which was not carried into space. Fortunately, male sterile plants
      were discovered in one of the ear rows. The stability of male sterile expression
      was observed in different years, different locations and different generations.
      In order to analysis the genetic characteristic of male sterility, test cross,
      sister cross, back cross, reciprocal cross and self-pollination were conducted
      with these male sterile plants. The results showed that the male sterility was
      stable in different years and different locations, it is inheritable from
      generation to generation. The sterility is controlled by a single nuclear
      recessive gene. The appearance of male sterile mutant is the conclusion of gene
      mutation which happened in nuclear by space flight. This mutant material always
      accompanies with lower plant height.

PMID- 14577373
TI  - [Cloning and characterization of the PTS2 receptor gene (GhPex7) from cotton
      (Gossypium hirsutum L.)].
AB  - Peroxisomal targeting signals (PTS), including PTS1 and PTS2, were proposed to
      play an important role in introducing proteins into the peroxisomal matrix. Pex7,
      the PTS2 receptor, is crucial to the import of PTS2 proteins. Based on the
      sequence of a fragment (F010) recovered from cDNA-AFLP, the full-length cDNA
      sequence was obtained by RACE and the contig in cotton ESTs, and the coding
      sequence was further cloned. The GhPex7 cDNA, 1314 bp in length, contained 5 non
      coding (77 bp) upstream, 3 complete downstream with polyA signal tail and ORF of
      954 bp, which coded for a deduced protein of 317 amino acids. The deduced protein
      had a predicted MW 35.57 kDa and a pI of 5.603. Homology analysis demonstrated
      that GhPex7 protein contained three highly conserved domains and three G-bata
      domains of WD-40 proteins family. The sequence of nucleotides and amino acids
      shared 83% and 76% identity with known Arabidopsis AtPex7, respectively, and its
      amino acid sequence shared from 28% to 42% identity with those of Drosophila
      melanogaster, Saccach, cerevisiae, Mus musculus and Homo sapiens. Southern
      blotting suggested that at least two copies of GhPex7 gene existed in Gossypium
      hirstum genome. By Northern blotting and RT-PCR analysis, expression of the
      GhPex7 was detected in roots, stems, leaves, buds, ovules and fibers, however it
      was stronger in leaves and stems than in other tissues. At the stage of cotton's
      ovules and fibers development, RT-PCR analysis also indicated that expression
      activity of GhPex7 in ovule at 0DPA mutant plant (no-fiber) was stronger than in
      wild type plant, its expression in wild type fiber at 23DPA was stronger than at
      12, 16 DPA too.

PMID- 14577374
TI  - Research on the genetic variations of a1-fucosytransferase (FUT1) gene in 26 pig
      breeds.
AB  - Enterotoxigenic Escherichia coli F18(ECF18) is a main pathogen that causes edema
      disease and post-weaning diarrhoea in piglets, and al-fucosytransferase (FUT1)
      gene has been identified as a candidate gene for controlling the expression of
      the receptor for ECF18 bacteria. The genetic variations at position 307
      nucleotide in open reading frame of FUT1 gene in 26 pig breeds (total 1458
      individuals) from 5 western commercial pig breeds and 21 Chinese native pig
      breeds were investigated by PCR-RFLP. The results showed that the genetic
      polymorphisms of the FUT1 locus were only detected in 5 western pig breeds and
      the Chinese Lingao pig breed, 5 western pig breeds possessed 3 different
      genotypes, and Lingao pig breed had two susceptible genotypes GG and AG, while
      all the other 20 Chinese native pig breeds only presented the susceptible
      genotype GG. The results indicated that if M307G-A point mutation in the coding
      region of FUT1 gene was the key factor determining the expression of the ECF18
      receptor, most of Chinese native pig breeds were absent of the genetic background
      on the resistance to ECF18 bacteria. In this case, it was inferred that the
      resistance gene to ECF18 might be originated from western pig breeds. In
      addition, it is of great importance for the conservation of Lingao pig breed as
      it is the only found Chinese native pig breed possessing resistance M307A allele
      in FUT1 gene. Generally, compared with exotic pig breeds, Chinese native pig
      breeds have stronger resistance to edema disease and post-weaning diarrhoea in
      piglets. The results suggested that further study should be done to identify and
      characterize putative QTL (quantitative trait locus) or/and the functional gene
      responsible for the resistance to ECF18 in Chinese native pig breeds.

PMID- 14577375
TI  - Genetic effects of IGF-1 gene on the performance in Landrace x Lantang pig
      resource population.
AB  - A Landrace x Lantang resource population (LL-SCAU) including 216 F2 pigs was
      founded by F2 design for analysis of IGF-1 gene polymorphism by PCR-RFLP. The
      least square means of divergent IGF-1 genotypes for the measured traits were
      estimated with the fixed model. The genetic effects of IGF-1 gene were estimated
      with a mixed model and the additive and dominant effects of IGF-1 gene were
      accordingly calculated. The results of the fixed model and the mixed model showed
      that IGF-1 locus significantly affected average daily gain after weaning. Average
      daily gain after weaning for AA genotype on IGF-1 locus was 20.58 g (P = 0.0347)
      higher than for AB. The additive and dominant effects attributed to IGF-1 were
      1.78 g and -18.81 g respectively. IGF-1 locus also significantly affected carcass
      composition. Bone percentages for AA and AB on IGF-1 locus were lower than for BB
      by 5.22% (P = 0.0008) and 5.19% (P = 0.0007) respectively, and the additive and
      dominant effects were -2.61% and -2.58% respectively. Amount of carcass lean for
      AA on IGF-1 locus was less than for AB by 0.45 kg (P = 0.0264), and the additive
      and dominant effects were 0.16 kg and 0.61 kg respectively. Skin and fat
      percentage for AA and AB on IGF-1 locus was higher than for BB by 8.81% (P =
      0.0206) and 7.64% (P = 0.0431) respectively, and the additive and dominant
      effects were 4.41% and 3.24% respectively. The genetic analysis of IGF-1 gene
      showed that IGF-1 locus significantly affected average daily gain after weaning,
      bone percentage, carcass lean, skin and fat percentage. The estimated additive
      and dominant effects showed that only the additive effect of IGF-1 locus on skin
      and fat percentage was much higher than dominant effect, and IGF-1 gene can be
      used as a major gene for effective selection of these traits.

PMID- 14577376
TI  - [Expression of mRNAs for GHR, IGF-IR, FSHR and LHR in granulosa and theca layers
      of ovarian follicles of Shaoxing ducks].
AB  - Expression of genes encoding growth hormone receptor (GHR), type I insulin-like
      growth factor receptor (IGF-IR), follicle-stimulating hormone receptor (FSHR) and
      luteinizing hormone receptor (LHR) was measured in granulosa and theca layers of
      the largest (F1), third largest (F3), fifth largest (F5) preovulatory follicles
      and large white follicles (LWF) in the ovary of Shaoxing ducks, with relative
      quantitative reverse transcription-polymerase chain reaction (RT-PCR) using beta
      actin as an internal standard. The results showed that GHR mRNA was more abundant
      in theca layer than in granulosa layer in all the follicles investigated, in
      theca layer, the LWF follicle expressed highest the level of GHR mRNA, while no
      differences in granulosa layer were observed among follicles at different stages
      of development. In contrast, the expression of IGF-IR mRNA in theca layer was
      evidently lower than that in granulosa layer, but no significant changes were
      found among different stages of follicles in either layers, except that LWF
      trended to express higher IGF-IR mRNA in the theca layer compared to other
      preovulatory follicles. Similar to IGF-IR mRNA, FSHR mRNA was more abundant in
      granulosa layer and no significant differences were found among different stages
      of follicles in either layers. In contrast, the expression of LHR mRNA followed a
      different pattern. In the theca layer, the expression level maintained
      consistent, while in the granulosa layer, a significant stepwise increase was
      observed as the follicles matured, resulting in higher mRNA level of LHR in the
      granulosa layer of largest follicles (F1), but lower mRNA level of LHR in the
      granulosa layer of smaller follicles (F5 and LWF). These results suggest that GH
      and IGF-I regulate ovary function by respective dominant sites in the follicles,
      and they cooperate with LH and FSH to regulate the follicle development via their
      respective receptors. The high expression of LHR mRNA in granulosa layer of large
      follicles might be related to the establishment of the follicle hierarchy and
      ovulation.

PMID- 14577377
TI  - [Microsatellite analysis of genetic diversity and phylogenetic relationship of
      eight sheep breeds in Xinjiang].
AB  - To reveal the genetic diversity and syseighttemic relationship of main sheep
      breeds in north Xingjiang, the genetic polymorphisms of 10 microsatellites in 8
      sheep breeds and one first filial generation (F1) in north Xinjiang were studied
      by means of PCR, polyacrylamide gel electrophoresis and silver staining. Number
      of alleles, average effective number of alleles (E) and average rates of
      homozygote of each breeds were counted. According to allele frequencies of ten
      microsatellites, polymorphism information content (PIC), mean heterozygosity (h)
      and genetic distances were calculated for each breeds. By using the Neighbor
      joining method of Molecular Evolutionary Genetics Analysis software, a dendrogram
      was obtained based on genetic distances. Another dendrogram was obtained by
      Maximum Likelihood method in PHYLIP (3.6) software. The bootstrap values were
      evaluated for each crunode of the dendrogram by means of bootstrap test. The
      systemic relationship was analyzed as well. The results showed that 8 of 10
      microsatellite loci were highly polymorphic, but BM1824 and MAF65 were low and
      medium polymorphic respectively, so the 8 microsatellite loci were effective
      markers for analysis of genetic relationship among sheep breeds. The average PIC
      (0.5631), h (0.5721) and E(2.9) of the whole population was all lower than those
      of other sheep breeds reported in the documents, which showed the gene
      polymorphisms and genetic diversity in these sheep breeds are relative rare. The
      genetic distances of native Aletai, Kazak and Bashibai sheeps in Xingjiang from
      foreign sheep breeds and cultivated breeds bearing foreign bloodline are
      relatively large. Consequently, they clustered in two groups. The phylogenetic
      relationship between different sheep breeds was in accordance with their
      resource, breeding history, differentiation and localities.

PMID- 14577378
TI  - [Analysis of genetic diversity of Shandong indigenous chicken breeds using
      microsatellite marker].
AB  - Microsatellite marker is one of the frequently used molecular markers. It has
      been used in the genotype identification, pedigree analysis and estimation of
      genetic distance. In this paper, five microsatellite markers with high
      polymorphisms were selected to detect the genetic diversity of seven chicken
      breeds. The alleles frequencies, polymorphism information content (PIC) and
      average heterozygosity within each population, and DA genetic distance among
      breeds were analyzed. The application of microsatellite polymorphisms to the
      detection of genetic variability and relationship among populations was
      discussed. Altogether, forty alleles were found in this experiment, and among
      them the most alleles (10) were detected by ADL0136 and the least (5) were
      detected by ADL0146. The distribution of alleles was not balanced, each locus
      having one or more dominant alleles. The average heterozygosity in the Shouguang
      chicken was the lowest (0.3327), and that in other breeds was also less than 0.4.
      It can be seen then that microsatellite polymorphisms can be used to reveal the
      variability within population through calculation of average heterozygosity. The
      PIC values ranged from 0.6169 (Shouguang chicken) to 0.7027 (Laiwu Black
      chicken). UPGMA tree was completed through analysis of DA genetic distance. In
      the tree, the Rizhao Pockmarked and the Jining Hundred chicken were first grouped
      together with a bootstrap value of 92%, before they were grouped with the Laiwu
      Black and the Shouguang chickens. The Anoka Yellow and the Guangxi Yellow chicken
      were grouped together with a bootstrap value of 80%, but the Luxi Fighting
      chicken had its own branch. In summary, the UPGMA tree well reflected the
      evolutionary and breeding history of the seven breeds.

PMID- 14577379
TI  - Cloning and characterization analysis of the genes encoding precursor of mast
      cell degranulating peptide from 2 honeybee and 3 wasp species.
AB  - The precursors of mast cell degranulating peptide (MCDP) genes were amplified by
      RT-PCR from the total RNA of venom gland of two honeybee species, Apis mellifera
      ligustica, Apis cerana cerana, and three wasp species, Vespa magnifica, Vespa
      velutina nigrothorax and Polistes hebraeus, respectively. Their PCR products were
      ligated into pGEM T-easy vector and the nucleotide sequences were analyzed. The
      length of five fragments was the same, it was 341 bp containing an ORF of 153 bp
      coding the precursor of MCDP and 188 bp 3' noncoding region. They have more than
      90% homologues with each other in nucleotide sequences. The precursors of MCDP of
      A. cerana cerana, V. magnifica, V. velutina nigrothorax and P. hebraeus shared
      96%, 100%, 94% and 98% homology with A. mellifera ligustica, respectively. The
      two species of wasps, V. magnifica and V. velutina nigrothorax, contained the
      same MCDP as A. mellifera ligustica, though they belong to different families
      with quite different biological properties, while A. cerana cerana contained the
      different MCDP in their venom as A. mellifera ligustica though they belong to the
      same genus. The fifth amino acid residue of MCDP in A. cerana cerana and P.
      hebraeus is arginine, replacing the cysteine, an important disulfide bridges
      element, in the position as in A. mellifera ligustica.

PMID- 14577380
TI  - [Phylogenetic reconstruction of DNA polymerase X family].
AB  - Phylogeny within DNA polymerase X family requires a re-examination as the
      expansion of family members, particularly considering the enter of two
      entomopoxvirus(EPV) members. A total of 37 DNA polymerase core-domain
      sequences(SMART domain), which come from numerous species with different
      evolutional levels, including above two virus members, were analyzed. The result
      showed that, the phylogenetic relationship within this family basically assorted
      with the distribution status of used species, of which two virus members and DNA
      polymerase beta(pol beta) of eukaryote were clustered together into sister group,
      indicating the likelihood that the two entomopoxviruses originated from
      eukaryote. The divergence time of subgroups, similarity of gene structure and
      conservation of syntenic genes were also analyzed, and evidences showed that, DNA
      polymerase mu (pol mu) is only present in Mammals, and as a recently occured
      duplication-gene of terminal deoxynucleotidyl transferase(TdT).

PMID- 14577381
TI  - [Origin of Hakka and Hakkanese: a genetics analysis].
AB  - Hakka is a distinctive Han Chinese population in Southern China speaking
      Hakkanese. The origin of Hakka has been controversial. In this report, we
      analyzed Y chromosomal markers in 148 Hakka males. Principle component analysis
      of Y-SNP haplotype distribution shows Hakka is clusteed strongly with the Han in
      Northern China, and is also close to She, a Hmong-Mien-speaking population, while
      the general Southern Han is fairly close to Daic populations. Admixture analysis
      revealed that the relative genetic contribution 80.2% (Han), 13% (She) and 6.8%
      (Kam) in Hakka. The network of Y-STR haplotype of M7 individuals in all concerned
      populations suggested two possible origins of Hmong-Mien contribution in Hakka:
      One is from Hubei and the other is from Canton. The Kam contribution in Hakka is
      likely from Kan-Yue, the ancient aborigine of Kiangsi (Jiangxi). The frequency of
      9bp-deletion in Region V of mitochondrial DNA of Hakka is 19.7%, which is quite
      close to She but far from Han. We therefore concluded that genetically the
      majority of Hakka gene pool shall come from North Han with She contributing the
      most among all non-Han groups. Regarding the Hmong-Mien character of Hakkanese,
      the genetic structure of Hakka shows their core may be Kim-man, the ancient Hmong
      Mien. We hypothesized that a great number of Han people from North China join
      this population in succession. Southern Chinese dialects, such as Hakkanese may
      also be those languages of Southern aborigines at first, and turn to extant
      appearance under the continuance effect of Northern Chinese.

PMID- 14577382
TI  - [Application of atomic force microscopy in the study of morphology of double
      minute chromosomes].
AB  - Atomic force microscopy (AFM) has many advantages in the study of biological
      samples, such as the convenient specimen preparation and the high resolution. In
      the present study, AFM was used to observe the double minute chromosomes (DMs) in
      mouse methotrexate-resistant cell line 3T3R500. AFM images were obtained by
      tapping mode, contact mode and later force mode of AFM. DMs were composed of two
      compact spheres connected with fibers. The number of DMs in the 3T3R500 cells
      increased with increasing levels of methotrexate (MTX) resistance. The data of
      the height and the underside diameter of the DMs were also obtained. The details
      of specimen preparation and scan mode selection of AFM were discussed. Our
      results show that AFM is a powerful method in the study of DMs.

PMID- 14577383
TI  - [Progress in molecular biology study of DNA computer].
AB  - DNA (deoxyribonucleotide acids) computer is an emerging new study area that
      basically combines molecular biology study of DNA molecules and computational
      study on how to employ these specific molecules to calculate. In 1994 Adleman
      described his pioneering research on DNA computing in Science. This is the first
      experimental report on DNA computer study. In 2001 Benenson et al published a
      paper in Nature regarding a programmable and autonomous DNA computing device.
      Because of its Turing-like functions, the device is regarded as another milestone
      progress for DNA computer study. The main features of DNA computer are massively
      parallel computing ability and potential enormous data storage capacity.
      Comparing with conventional electronic computers, DNA molecules provide
      conceptually a revolution in computing, and more and more implications have been
      found in various disciplines. DNA computer studies have brought great progress
      not only in its own computing mechanisms, but also in DNA manipulation
      technologies especially nano-technology. This article presents the basic
      principles of DNA computer, its applications, its important relationship with
      genomic research and our comments on all above issues.

PMID- 14577384
TI  - Rural hospital HIPAA readiness and resource needs.
AB  - PRINCIPAL FINDING: rural hospitals with fewer than 50 beds were most in need of
      assistance and resources to prepare for HIPAA indicating that the Small Hospital
      Improvement Program chose well in making HIPAA readiness one of three purposes
      for grants to those hospitals.

PMID- 14577385
TI  - Enrollment in FEHBP plans in rural America: what are the implications for
      Medicare reform?
AB  - In places where the competing health plans are unlikely to ever emerge, any
      policy predicated on assumptions that competing plans will deliver health
      insurance benefits needs to have a "fallback" option that is guaranteed to work.

PMID- 14577386
TI  - Building a foundation for evidence-based practice: experiences in a tertiary
      hospital.

PMID- 14577387
TI  - Providing free smoke alarms did not reduce fire related injuries in a deprived
      multiethnic urban population.

PMID- 14577388
TI  - Review: self management education improves outcomes in children and adolescents
      with asthma.

PMID- 14577389
TI  - Review: regular medical review is not better than written self management plans
      for optimising asthma control.

PMID- 14577390
TI  - Review: day hospital is as effective as inpatient care but has lower costs for
      patients with acute psychiatric disorders.

PMID- 14577391
TI  - Treatment of hypertension reduces risk of complications in type 2 diabetes.

PMID- 14577392
TI  - An intensive, target driven intervention reduced cardiovascular and microvascular
      events in patients with type 2 diabetes and microalbuminuria.

PMID- 14577393
TI  - A COPD self management programme reduced hospital use and improved health status.

PMID- 14577394
TI  - Review: several interventions prevent ventilator associated pneumonia in
      critically ill patients.

PMID- 14577395
TI  - Oral vitamin D3 supplementation reduced fractures in community dwelling elderly
      people.

PMID- 14577396
TI  - A multifactorial intervention after a fall did not prevent falls in elderly
      patients with cognitive impairment and dementia.

PMID- 14577397
TI  - A structured education programme increased hip protector use and may reduce hip
      fractures in nursing homes.

PMID- 14577398
TI  - Resistance exercises or vitamin D did not improve physical health or reduce falls
      in frail older people.

PMID- 14577399
TI  - Characterization of the testicular binding site for iodinated rat FSH in the
      turtle, Chrysemys picta.
AB  - 1. To correlate the morphological observations with the known gonadotropic
      activity of FSH in the turtle testis, studies of the binding of iodinated FSH
      were conducted. 2. These demonstrated the presence of gonadotropin-binding sites
      of high affinity (apparent Kd = 10(-10) M) for [125I]rFSH in turtle testicular
      membrane preparations. 3. Although these sites did not bind iodinated human LH or
      avian LH, these hormones, as well as PMSG and FSH, were effective competitive
      inhibitors of the binding of the radioligand. 4. Binding of the radioligand to
      the testis was influenced by duration of incubation and temperature. 5. Binding
      activity was lost after incubation with proteolytic enzymes (trypsin, pronase)
      but not with DNAase, lipase, collagenase and neuraminidase. 6. The binding
      exhibited target organ specificity (no binding observed in brain, epididymis,
      lung, muscle and pancreas). 7. In addition, the number of binding sites varied
      according to the stage spermatogenesis, being highest when the tubules contained
      spermatocytes and spermatids, intermediate when the tubules consisted to Sertoli
      cells and spermatogonia and lowest st spermiation.

PMID- 14577400
TI  - An exercise and incontinence intervention did not reduce the incidence or cost of
      acute conditions in nursing home residents.

PMID- 14577401
TI  - The SCOFF questionnaire was less sensitive but more specific than the ESP for
      detecting eating disorders.

PMID- 14577402
TI  - Needing help to use a toilet was associated with faecal incontinence at 3 months
      in new onset faecal incontinence after stroke.

PMID- 14577403
TI  - Eating alone, parents' marital status, and use of radio and girls' magazines were
      risk factors for eating disorders.

PMID- 14577405
TI  - Preoperative assessments by trained nurses were equal in quality to assessments
      by preregistration house officers.

PMID- 14577404
TI  - Intentional weight loss was associated with lower mortality, whereas
      unintentional weight loss was associated with increased mortality.

PMID- 14577406
TI  - The benefits of nurse led secondary prevention clinics for coronary heart disease
      continued after 4 years.

PMID- 14577407
TI  - Individuals taking combination therapies for HIV or AIDS faced barriers to
      remaining in, or returning to work.

PMID- 14577408
TI  - Living with untreated localised prostate cancer was seen as living under a dark
      shadow.

PMID- 14577410
TI  - Women with ovarian cancer described waiting for recurrence, facing the diagnosis
      of recurrence, managing treatment related concerns, and attempting to regain
      control.

PMID- 14577409
TI  - Women living with ovarian cancer described changes in day to day living, major
      challenges, and sources of support.

PMID- 14577411
TI  - Organ scaling in the raccoon dog Nyctereutes procyonoides gray 1834, as monitored
      by influences of internal and external factors.
AB  - 1. Animals fed a high energy ration had bigger body weight, and bigger heart,
      brain and genitals then animals fed a normal diet, but they had substantially
      smaller liver, kidneys, adrenals and thyroid glands than the otherwise smaller
      animals. Restricted feeding did not necessarily produce smaller organ sizes than
      normal. 2. The yearly variation in organ sizes was astonishingly large whereas
      the sex differences were rather rare. 3. For organs like liver, kidneys and
      thyroid glands the conclusion from the results was independent of the method of
      expressing the organ mass. The organ sizes seemed to be influenced by many
      coexisting factors like yearly differences, sex and age of animals, feed and
      farm.

PMID- 14577412
TI  - Parents of adult children with schizophrenia dealt with societal objections in
      order to provide the necessary care.

PMID- 14577413
TI  - The decline of sugar maples (Acer saccharum).

PMID- 14577414
TI  - The Bohr effect of the blood in rainbow trout (Salmo gairdnerii). A comparative
      study with human blood, using precise oxygen equilibrium curves and the Adair
      model.
AB  - 1. The Bohr effects of trout blood (which exhibits the Root effect) and of human
      blood were compared. Precise oxygen equilibria were measured with an automatic
      recording system, on normal trout red blood cell suspensions at pH 7.6 - 8.6, at
      10 and 20 degrees C, and on normal human red blood cell suspensions at pH 6.8 -
      8.0, at 37 degrees C. 2. The data were fitted to the Adair's stepwise oxygenation
      model which describes experimental curves with four constants ki (i = 1-4). 3.
      Adair's scheme successfully fits the equilibrium data for trout and human blood,
      in the range of conditions examined. 4. The R-state Bohr effect (d log k4/ d pH),
      is very large in trout blood, indicating a large pH dependence of the R
      structure, as opposed to human blood. 5. The T-state Bohr effect (d log k1/ d
      pH), and the overall Bohr effect (d log Pm/ d pH), are equivalent in trout and
      human blood. 6. The overall Bohr effect is essentially accounted for by the first
      and fourth oxygenation steps in trout blood and shows a significant effect of
      temperature. 7. The data attribute a major role to Hb4 in trout blood isotherms
      and confirm the importance of the C-termini of Beta chains in Bohr and Root
      effects.

PMID- 14577415
TI  - Prolonged modification of action potential shape by synaptic inputs in molluscan
      neurones.
AB  - 1. Somatic action potentials of Lymnaea neurons are modified by excitatory or
      inhibitory synaptic inputs and have been studied using phase-plane techniques and
      an action potential duration monitor. 2. Excitatory synaptic inputs increase the
      rate of neuronal discharge, cause action potential broadening, a decrease in the
      maximum rate of depolarization (Vd) and a decrease in the maximum rate of
      repolarization (Vr). 3. Inhibitory synaptic inputs decrease the discharge rate
      and cause narrowing of action potentials, an increase in Vd and an increase in
      Vr. 4. The effects reported above outlast the original synaptic inputs by many
      seconds and, if the somatic action potentials are similar to those in the axon
      terminals, they may have far-reaching effects on transmitter release.

PMID- 14577416
TI  - Proximity to service providers and service utilization among welfare recipients:
      the interaction of place and race.
AB  - Currently, welfare programs coordinate a range of services to support work among
      welfare recipients and help them overcome barriers to employment. This paper
      considers the relationship between spatial proximity to and utilization of
      support services among welfare recipients. Accessibility of mental health and
      substance abuse service providers among welfare recipients is examined in the
      three-county Detroit metropolitan area and the relationship between mental health
      service accessibility and mental health service utilization among welfare
      recipients considered. Not only does access to service providers vary
      significantly across the metropolitan area by race and place, but these analyses
      reveal that greater spatial proximity to service providers increases the
      probability that welfare recipients will receive services. When controlling for
      access to providers and individual-level characteristics, we also find that
      African American welfare recipients are about half as likely to use mental health
      services as white recipients.

PMID- 14577417
TI  - Insured Americans drive surge in emergency department visits.
AB  - Visits to hospital emergency departments (EDs) have increased greatly in recent
      years, contributing to crowded conditions and ambulance diversions. Contrary to
      the popular belief that uninsured people are the major cause of increased
      emergency department use, insured Americans accounted for most of the 16 percent
      increase in visits between 1996-97 and 2000-01, according to a study by the
      Center for Studying Health System Change (HSC). This Issue Brief examines trends
      in emergency department and other ambulatory care use, focusing on differences
      among insurance groups. Although insured people accounted for most of the
      increase in emergency department visits, uninsured Americans increasingly rely on
      emergency departments because of decreased access to other sources of primary
      medical care. Emergency department waiting times also have increased
      substantially, which may lower both insured and uninsured patients' perceptions
      of the quality of their care.

PMID- 14577418
TI  - [Considerations against the use of EPO in the acute treatment of stroke].

PMID- 14577420
TI  - [Interleukin-4: a new option in the therapy of systemic psoriasis?].

PMID- 14577419
TI  - [The treatment of keloids].
AB  - Keloids are benign fibrous growths with characteristic clinical features, whose
      underlying pathogenic mechanisms are not fully understood. While numerous
      treatment approaches are available, there is little evidence for efficacy based
      on controlled clinical studies. Therapeutic results are often not satisfactory.
      The best approach employs multiple modalities appropriate for the stage of the
      lesion. Combining invasive methods such as cryotherapy, surgery, intralesional
      steroid injections, laser or radiotherapy with external or physical approaches
      has helped to optimize treatment efficacy. Newer clinical studies with
      intralesional substances such as interferons which may directly influence
      collagen metabolism show promising results; these substances may be valuable
      therapeutic additions.

PMID- 14577421
TI  - Protecting the nation's military may include the use of investigational new
      drugs.

PMID- 14577422
TI  - Protecting the public's health in an era of bioterrorism: the Model State
      Emergency Health Powers Act.
AB  - During the fall of 2001, public health law scholars at the Center for Law and the
      Public's Health at Georgetown and Johns Hopkins Universities were asked by the
      Centers for Disease Control and Prevention (CDC) and a series of national
      partners to develop the Model State Emergency Health Powers Act (MSEHPA). The
      MSEHPA provides a series of modern powers for states to consider in responding to
      catastrophic public health emergencies, including bioterrorism events. Since
      December 2001, provisions based on the MSEHPA have been introduced in nearly 40
      states and passed in 20. Underlying the development of the act is a long-standing
      debate between legal and ethical scholars and law- and policymakers as to the
      appropriate ways to balance individual and communal rights. The drafting
      challenge was to create a comprehensive model law that provides adequate powers
      to protect the public's health while also respecting individual and group rights.
      The MSEHPA empowers public health agents with broad authority and simultaneously
      limits the exercise of power in time, duration, and scope to accomplish communal
      goals of abating serious public health threats. Coercive public health powers,
      particularly isolation and quarantine, are exercised on a temporary basis, only
      so long as are reasonably necessary and only among persons who justifiably may
      pose a risk to others because of their contagious conditions. Individual rights
      to contest the coercive use of public health powers, even during an emergency,
      are secured.

PMID- 14577423
TI  - Balancing pluralism and the common good: a look at open-air experiments of
      biowarfare agents.

PMID- 14577424
TI  - From Baltimore to Bell Labs: reflections on two decades of debate about
      scientific misconduct.
AB  - This essay proposes a new definition of scientific "misconduct," which is broader
      than the definition recently adopted by the U.S. government. According to the
      proposed definition, misconduct is a serious and intentional violation of
      accepted scientific practices, commonsense ethical norms, or research regulations
      in proposing, designing, conducting, reviewing, or reporting research. Punishable
      misconduct includes fabrication of data or experiments, falsification of data,
      plagiarism, or interference with a misconduct investigation. Misconduct does not
      include honest errors, differences of opinion, or ethically questionable research
      practices.

PMID- 14577425
TI  - 9 IT healthcare information technology innovators.

PMID- 14577426
TI  - Does grief counseling work?
AB  - Most bereavement caregivers accept as a truism that their interventions are
      helpful. However, an examination of the bereavement intervention literature
      suggests that the scientific basis for accepting the efficacy of grief counseling
      may be quite weak. This article summarizes the findings of four recent
      qualitative and quantitative reviews of the bereavement intervention literature.
      It then discusses three possible explanations for these surprising findings and
      concludes with recommendations for both researchers and clinicians in thanatology
      that could help to focus efforts to answer the questions of when and for whom
      grief counseling is helpful.

PMID- 14577427
TI  - Gallstone ileus diagnosed by computed tomography.

PMID- 14577428
TI  - FDA alerts asthmatics to drug safety risk.

PMID- 14577429
TI  - A shore thing.

PMID- 14577430
TI  - The worm has turned.

PMID- 14577431
TI  - How to step out of line and not step out of your job.

PMID- 14577432
TI  - [Choroid melanoma. Proton rays save the eyesight].

PMID- 14577433
TI  - End-of-life issues as perceived by Lebanese judges.
AB  - OBJECTIVES: to assess the attitudes of judges in Beirut, Lebanon, regarding end
      of-life issues such as assisted suicide and withholding or withdrawing life
      sustaining treatment. SUBJECTS AND METHODS: 85% of all currently acting and in
      training judges and public prosecutors in Beirut (N=135) were surveyed using a
      mailed questionnaire that assessed attitudes toward intervention in five
      hypothetical cases. The associations of attitudes, on a scale from least to most
      'sympathetic' toward assisting those who desire to end their lives, were measured
      by a variety of personal, social and professional variables. RESULTS: younger
      individuals, and those who have not yet been formally appointed as judges, were
      significantly more sympathetic to withdrawal or withholding of life-sustaining
      devices when patients or their proxies requested it, and more in support of
      assisted suicide. Gender, religious denomination, religious practice, and
      personal experience with prolonged illness leading to death among close friends
      or family, were generally not significant predictors of respondents' attitudes.
      Years of experience as a judge correlated strongly with age and may have
      contributed to its predictive effect. DISCUSSION AND CONCLUSIONS: a relatively
      more sympathetic attitude among younger judges, many of them women, and among
      trainees, may reflect a historical evolution in younger age-groups in Lebanon
      today. A survey of opinions in the public may help reach a more conclusive
      understanding in this regard. In any case, judges in Lebanon will remain
      important partners in the debate, as they will continue to be the final
      interpreters of the letter of the law in end-of-life issues.

PMID- 14577434
TI  - Who--and how--to kill are focus of US death penalty cases. Questions about
      prisoners' mental competence and use of pancuronium bromide ignite recent
      controversy.

PMID- 14577435
TI  - Struggling to rebuild Iraq's health-care system. War, sanctions, and
      mismanagement have left health system in shambles.

PMID- 14577436
TI  - Canadian infection-control experts push for health reform.

PMID- 14577437
TI  - Canada to change patent law to allow export of cheap drugs.

PMID- 14577438
TI  - Report finds shortage of US physicians by 2020.

PMID- 14577439
TI  - Care of learning-disabled Russian children condemned.

PMID- 14577440
TI  - Indian experts favour IPV to eradicate polio.

PMID- 14577441
TI  - EU urged to create European Research Council.

PMID- 14577442
TI  - China makes preparations for possible new SARS outbreak. Measures include
      improved training, more hospital beds, and a better national reporting system.

PMID- 14577443
TI  - The ineffectiveness of retrospective drug utilization review.
AB  - As policymakers debate adding a prescription drug benefit to Medicare, they must
      also seek ways to promote cost-effective use of drugs and minimize inappropriate
      prescribing. For more than a decade, all state Medicaid agencies and most private
      insurers have used computerized drug utilization review (DUR) programs to prevent
      or rectify potential prescribing errors. DUR can be retrospective, in which
      claims data are reviewed to identify patterns of drug use, or prospective, in
      which prescriptions are reviewed before a drug is dispensed. This Issue Brief
      summarizes a landmark study that suggests that retrospective DUR has had no
      measurable effects on outpatient drug use or clinical outcomes in the Medicaid
      program.

PMID- 14577444
TI  - ["Evidence-based" medicine].

PMID- 14577446
TI  - [Evidence-based cariology].

PMID- 14577445
TI  - The politics of grief and continuing bonds with the dead: the cases of Maoist
      China and Wahhabi Islam.
AB  - The article is a contribution to a cross-cultural theory of grief. It examines
      the relationship between individual/family continuing bonds with the dead and
      cultural narratives that legitimize political power. The dead are collective
      representations (Dirkheim) that mediate the larger culture to individuals and to
      smaller communities and that reinforce social solidarity and identity. The
      political question is which collective--family, community, church, party, nation-
      owns the dead and controls the rituals by which bonds with the dead are
      maintained or relinquished? The article discusses one historical condition: times
      of rapid change in power arrangements. Bonds with the dead have a power in
      individual, family, or tribal life that can threaten the narrative that
      legitimizes the new political power holders. Ancestor rituals that support
      identity as a family or tribal member are surpressed and replaced by allegiance
      to collective representations of the new political order. Two historical examples
      are given: China under Chairman Mao and the Wahhabi reform in Arabic Islam.

PMID- 14577447
TI  - The cost of the muse: poets die young.
AB  - Although several investigations have found that poets tend to die younger than
      other types of writers, these studies often do not take into account variables of
      gender and culture. This study examines 1,987 deceased writers from four
      different cultures: American, Chinese, Turkish, and Eastern European. Both male
      and female poets had the shortest life spans of all four types of writers
      (fiction writers, poets, playwrights, and non-fiction writers), and poets had the
      shortest life spans in three of the four cultures (and the second shortest life
      span among Eastern European writers). Possible reasons for the poet's shorter
      life span are then discussed.

PMID- 14577448
TI  - [Digital libraries, home access to the literature].

PMID- 14577449
TI  - Effects of sentencing options and strict / lenient instructions on convicting
      suicide attempters.
AB  - Sentence and strictness of instructions influence juries' willingness to convict.
      To see whether this result holds for suicide attempters, 240 undergraduates read
      jury instructions for a suicide attempt that varied sentence (jail term, fine,
      community service, or mandatory counseling) and instructions, voted guilty / not
      guilty, and rated their certainty and effectiveness. With sentences of 25 hours
      mandatory counseling, or strict instructions, more respondents voted guilty.
      Sentence did not impact certainty or effectiveness, but strictness enhanced
      certainty. Overall, respondents were neutral that convicting a suicide attempter
      would reduce future attempts. Consistent with terror management theory, present
      students were willing to punish regardless of whether they thought that the
      punishment was preventive.

PMID- 14577450
TI  - Effect of convective disturbances induced by g-jitter on the periodic
      precipitation of lysozyme.
AB  - Numerical simulations are carried out to investigate the crystallization process
      of a protein macromolecular substance under two different conditions: pure
      diffusive regime and microgravity conditions present on space laboratories. The
      configuration under investigation consists of a protein reactor and a salt
      chamber separated by an "interface". The interface is strictly related to the
      presence of agarose gel in one of the two chambers. Sedimentation and convection
      under normal gravity conditions are prevented by the use of gel in the protein
      chamber (pure diffusive regime). Under microgravity conditions periodic time
      dependent accelerations (g-jitter) are taken into account. Novel mathematical
      models are introduced to simulate the complex phenomena related to protein
      nucleation and further precipitation (or resolution) according to the
      concentration distribution and in particular to simulate the motion of the
      crystals due to g-litter in the microgravity environment. The numerical results
      show that gellified lysozyme (crystals "locked"on the matrix of agarose gel)
      precipitates to produce "spaced deposits". The crystal formation results
      modulated in time and in space (Liesegang patterns), due to the non-linear
      interplay among transport, crystal nucleation and growth. The propagation of the
      nucleation front is characterized by a wave-like behavior. In microgravity
      conditions (without gel), g-jitter effects act modifying the phenomena with
      respect to the on ground gellified configuration. The role played by the
      direction of the applied sinusoidal acceleration with respect to the imposed
      concentration gradient (parallel or perpendicular) is investigated. It has a
      strong influence on the dynamic behaviour of the depletion zones and on the
      spatial distribution of the crystals. Accordingly the possibility to obtain
      better crystals for diffraction analyses is discussed.

PMID- 14577451
TI  - The dilemma of intellectual property rights for pharmaceuticals: the tension
      between ensuring access of the poor to medicines and committing to international
      agreements.
AB  - In this paper, we provide an overview of how the outcomes of the Uruguay Round
      affected the application of pharmaceutical intellectual property rights globally.
      Second, we explain how specific pharmaceutical policy tools can help developing
      states mitigate the worst effects of the TRIPS Agreement. Third, we put forward
      solutions that could be implemented by the World Bank to help overcome the divide
      between creating private incentives for research and development of innovative
      medicines and ensuring access of the poor to medicine. Fourth, we evaluate these
      solutions on the basis of utilitarian considerations and urge that equitable
      pricing is morally preferable to the other solutions.

PMID- 14577452
TI  - Through a glass, darkly: data and uncertainty in the AIDS debate.
AB  - The HIV/AIDS epidemic is the greatest threat to development in much of Africa. It
      is already the main cause of death in many countries, especially those in
      Southern Africa. However there is an absence of solid data on the scale and scope
      of the disease and how it is evolving. In this article we discuss the data on the
      epidemic--where it comes from and how it is presented. We note the limitations of
      the use of antenatal clinic surveys--which provide the bulk of our information.
      We then turn to the evidence of impact. The paper shows that the long incubation
      period between infection and illness means that it takes time for HIV infections
      to turn into AIDS cases, and AIDS cases to translate into deaths with all the
      consequences of orphaning, poverty and changing population structures.
      Furthermore it means that once the HIV prevalence has peaked, AIDS impact will
      take years to work through--this epidemic is a 'long-wave' event. The paper is
      premised on the view that HIV causes AIDS and AIDS causes death. It notes that
      insufficient and/or unreliable data have allowed leaderships to deny the scope
      and scale of the problem and that this is unacceptable. However it is incumbent
      on all to accept the moral responsibility for and the moral consequences of their
      work, and this includes those who gather, interpret and use the data.

PMID- 14577453
TI  - [Study on constituents of buckwheat].

PMID- 14577454
TI  - The Steve Biko affair: a case study in medical ethics.
AB  - Steve Biko died in detention in South Africa in 1977. Critical ethical issues are
      raised both by the conduct of the doctors responsible for Biko's care and by the
      subsequent response of the medical profession as a whole. Because those issues
      are relevant to all healthcare professionals everywhere, the Biko affair provides
      a useful case study in medical ethics. We discuss the case in this article,
      describing how we use it in our teaching.

PMID- 14577455
TI  - "To become father and mother only through each other".

PMID- 14577456
TI  - Is there a common morality?

PMID- 14577457
TI  - Zones of consensus and zones of conflict: questioning the "common morality"
      presumption in bioethics.
AB  - Many bioethicists assume that morality is in a state of wide reflective
      equilibrium. According to this model of moral deliberation, public policymaking
      can build upon a core common morality that is pretheoretical and provides a basis
      for practical reasoning. Proponents of the common morality approach to moral
      deliberation make three assumptions that deserve to be viewed with skepticism.
      First, they commonly assume that there is a universal, transhistorical common
      morality that can serve as a normative baseline for judging various actions and
      practices. Second, advocates of the common morality approach assume that the
      common morality is in a state of relatively stable, ordered, wide reflective
      equilibrium. Third, casuists, principlists, and other proponents of common
      morality approaches assume that the common morality can serve as a basis for the
      specification of particular policies and practical recommendations. These three
      claims fail to recognize the plural moral traditions that are found in
      multicultural, multiethnic, multifaith societies such as the United States and
      Canada. A more realistic recognition of multiple moral traditions in pluralist
      societies would be considerable more skeptical about the contributions that
      common morality approaches in bioethics can make to resolving contentious moral
      issues.

PMID- 14577458
TI  - Common morality, coherence, and the principles of biomedical ethics.
AB  - The fifth edition of Beauchamp and Childress's Principles of Biomedical Ethics is
      distinguished by its emphatic embrace of common morality as the ultimate source
      of moral norms. This essay critically evaluates the fifth edition's discussion of
      common morality and, to a lesser extent, its treatment of coherence (both the
      model of ethical justification and the associated concept). It is argued that the
      book is overly accommodating of existing moral beliefs. The paper concludes with
      three suggestions for improving this leading text.

PMID- 14577459
TI  - Consistency, common morality, and reflective equilibrium.
AB  - Biomedical ethicists often assume that common morality constitutes a largely
      consistent normative system. This premise is not taken for granted in general
      normative ethics. This paper entertains the possibility of inconsistency within
      common morality and explores methodological implications. Assuming common
      morality to be inconsistent casts new light on the debate between principlists
      and descriptivists. One can view the two approaches as complementary attempts to
      evade or transcend that inconsistency. If common morality proves to be
      inconsistent, then principlists might have reason to prefer a less pluralist
      theory, thereby moving closer to descriptivism. Descriptivists, by contrast,
      might want to qualify their claim to accommodate all of people's basic moral
      convictions. Finally, both camps might wish to adopt a more revisionist posture,
      accepting that an adequate ethical theory occasionally will contradict some of
      people's deepest moral convictions. Proper application of the method of
      reflective equilibrium, to which both descriptivists and principlists claim
      allegiance, may entail greater openness to revisionism than either camp admits.

PMID- 14577461
TI  - Changing vocabularies: a guide to help bioethics searchers find relevant
      literature in National Library of Medicine databases using the Medical Subject
      Headings (MeSH) indexing vocabulary.

PMID- 14577460
TI  - A defense of the common morality.
AB  - Phenomena of moral conflict and disagreement have led writers in ethics to two
      antithetical conclusions: Either valid moral distinctions hold universally or
      they hold relative to a particular and contingent moral framework, and so cannot
      be applied with universal validly. Responding to three articles in this issue of
      the Journal that criticize his previously published views on the common morality,
      the author maintains that one can consistently deny universality to some
      justified moral norms and claim universality for others. Universality is located
      on the common morality and nonuniversality in other parts of the moral life,
      called "particular moralities." The existence of universal moral standards is
      defended in terms of: (1) a theory of the objectives of morality, (2) an account
      of the norms that achieve those objectives, and (3) an account of normative
      justification (both pragmatic and coherentist).

PMID- 14577462
TI  - [Surgical professorship appointments in Germany. Requirements for professorship
      applicants in general and visceral surgery].

PMID- 14577463
TI  - [Gastroenterology and visceral surgery. 2 societies formulate common goals].

PMID- 14577464
TI  - Serology: recent developments, strengths, limitations and prospects: a state of
      the art overview.
AB  - Specific antibodies can be used as a surrogate marker for bacterial load in
      leprosy. Tests to detect antibodies can be used for (i) the classification of
      patients for treatment purposes [most multibacillary (MB) patients are
      seropositive, most paucibacillary (PB) patients are not], (ii) the prediction of
      an increased risk of relapse and (iii) the identification of contacts having an
      increased risk of developing leprosy. With the advent of fast, robust and easy to
      perform serological tests such as lateral flow, agglutination and card tests, the
      application of serology in the field for these purposes becomes a feasible
      prospect. We hereby present an overview of the current knowledge and new
      developments in this area and discuss the strengths, limitations and possible
      applications of antibody detection in leprosy research and control.

PMID- 14577465
TI  - Thalidomide does not modify the ability of cells in leprosy patients to
      incorporate [3H]-thymidine when incubated with M. leprae antigens.
AB  - The immune response in reversal reaction, (RR) and in erythema nodosum leprosum
      (ENL) is characterized in vitro by an enhancement in lymphocyte blast
      transformation against M. leprae. As thalidomide is an effective treatment for
      ENL, this study assessed the effect of this drug on these phenomena. Mononuclear
      cells from patients attending the clinic at ALERT and from healthy staff were
      cultured for 5 days with integral M. leprae (IMl), or a modified Dharmendra
      antigen (Dhar), or PPD from M. tuberculosis. In one set of cultures, thalidomide
      was added once at the initiation of the culture; in the other set thalidomide was
      added a second time (2x), 18 h prior to harvesting the cells. The mononuclear
      cells, in the absence of thalidomide, from healthy staff, borderline tuberculoid
      patients (BT) and BT patients in RR (BT/RR) incorporated [3H]-thymidine best when
      cultured with PPD > Dhar > M. leprae. The cells from patients with ENL did not
      respond well to the M. leprae antigens. Thalidomide (2x) enhanced proliferation
      to Dhar in the BTRR group (Wilcoxon signed rank test, P < 0.05). No significant
      changes occurred for the other groups. Comparing PPD-stimulated cells treated
      with thalidomide once to those treated with thalidomide twice, thalidomide (2x)
      suppressed incorporation of [H3]-thymidine by the PPD-stimulated (P < 0.05) as
      well as IMl-stimulated (P < 0.05) cells in the healthy staff group. In the Dhar
      stimulated cells from the healthy staff thalidomide significantly suppressed TNF
      alpha (P < 0.05). A mixed effect was seen within and between the other groups,
      but there was a trend for thalidomide to suppress TNF-alpha induced by the M.
      leprae, Dhar and PPD antigens.

PMID- 14577466
TI  - Assessment of disability, social and economic situations of people affected by
      leprosy in Shandong Province, People's Republic of China.
AB  - With the decline in prevalence of leprosy, social and economic rehabilitation
      (SER) has become a major priority in leprosy control programme in Shandong
      Province. In the preparative phase of an SER programme, a province-wide survey
      was conducted with a semi-structured questionnaire in order to provide policy
      makers and programme managers with some basic information on the disability, and
      social and economic situation of the people affected by leprosy. This paper
      presents the results of a study in the people affected by leprosy living in the
      communities.

PMID- 14577467
TI  - Role of leprosy villages and leprosaria in Shandong Province, People's Republic
      of China: past, present and future.
AB  - In the late phase of the leprosy control programme in Shandong Province, People's
      Republic of China, there are a few old and disabled ex-patients living in 54
      leprosy villages/leprosaria. The small, and declining number of patients makes
      the running of these leprosy villages/leprosaria uneconomic. In this paper, we
      review the history and the role of leprosy villages/leprosaria in the care of
      leprosy patients and the control programme in Shandong province. We then analyse
      the present situation of the 643 people still living in these leprosy
      villages/leprosaria, using information collected from a questionnaire-based
      survey. Finally, we offer some suggestions and recommendations for policy makers
      and leprosy control managers, in order to improve the present situation and make
      better use of existing resources.

PMID- 14577468
TI  - Characteristics and treatment outcomes of leprosy patients detected during a
      leprosy elimination campaign in Mozambique compared with routinely detected
      patients.
AB  - The objective of this study is to assess whether the case-finding method is a
      determinant for diagnostic characteristics and treatment outcome of newly
      diagnosed leprosy patients in Northern Mozambique. This is a retrospective cohort
      study of 3202 patients on the differences between entrance characteristics and
      treatment outcome in self-reporting patients and patients detected during a
      leprosy elimination campaign (LEC) in 1999 in Northern Mozambique. As a
      consequence of LEC activities, 3 times more patients were found compared with the
      same period 1 year earlier. After the LEC, case detection remained higher in the
      years 2000-2002 compared with the years preceding the LEC. More young (<15 years)
      paucibacillary (PB) cases were diagnosed during LEC activities with,
      surprisingly, equal percentage of disability grades. No gender imbalance was
      found in diagnosed LEC patients contrary to self-reporting patient groups.
      Comparing patients detected during a LEC in 1999 with the passive group of 1998
      and 1999 showed a slight but statistically significant better treatment result
      for the passive group. The classification of leprosy (in favour of PB) and age
      (in favour of older age groups) were also determinants for favourable treatment
      outcomes. Volunteers had a significantly better result of treatment compared with
      trained nurses and regardless of detection method. LEC proved to be a useful
      addition to the National Leprosy and Tuberculosis Programme in Northern
      Mozambique. As a result, many new cases were diagnosed and put on treatment and
      their treatment results were very satisfactory. LEC had a lasting impact on case
      finding. Volunteers make a valuable contribution to leprosy control in Mozambique
      because they have consistently better treatment results compared with nurses.

PMID- 14577469
TI  - Screening for leprosy in immigrants--a decision analysis model.
AB  - Almost all leprosy cases reported in industrialized countries occur amongst
      immigrants or refugees from developing countries where leprosy continues to be an
      important health issue. Screening for leprosy is an important question for
      governments in countries with immigration and refugee programmes. A decision
      analysis framework is used to evaluate leprosy screening. The analysis uses a set
      of criteria and parameters regarding leprosy screening, and available data to
      estimate the number of cases which would be detected by a leprosy screening
      programme of immigrants from countries with different leprosy prevalences,
      compared with a policy of waiting for immigrants who develop symptomatic clinical
      diseases to present for health care. In a cohort of 100,000 immigrants from high
      leprosy prevalence regions (3.6/10,000), screening would detect 32 of the 42
      cases which would arise in the destination country over the 14 years after
      migration; from medium prevalence areas (0.7/10,000) 6.3 of the total 8.1 cases
      would be detected, and from low prevalence regions (0.2/10,000) 1.8 of 2.3 cases.
      Using Australian data, the migrant mix would produce 74 leprosy cases from 10
      years intake; screening would detect 54, and 19 would be diagnosed subsequently
      after migration. Screening would only produce significant case-yield amongst
      immigrants from regions or social groups with high leprosy prevalence. Since the
      number of immigrants to Australia from countries of higher endemnicity is not
      large routine leprosy screening would have a small impact on case incidence.

PMID- 14577470
TI  - Delayed diagnosis of leprosy and the potential role of educational activities in
      Brazil.
AB  - This study identifies possible obstacles to the early diagnosis of leprosy. Semi
      structured interviews were held with 40 patients at a secondary health service in
      upstate Sao Paulo, Brazil. The data concerning the sample were: 75% males, age
      range 13-76 years, 85% with elementary school education, 85% multibacillary. Skin
      lesions associated with sensory alterations had been noticed by 55% of the
      patients; 32.5% of the patients had been misdiagnosed as having conditions other
      than leprosy. The diagnosis was made 1 year after the awareness of signs/symptoms
      in 55% of the patients. In this group, 54% had impairment grade 1, while 23% had
      no disabilities. Forty-five percent of all patients interviewed had some
      information about the disease prior to diagnosis. Eleven patients (27.5%) had
      previous contact with leprosy patients, but this did not prevent late diagnosis
      in 64%. After the disease was confirmed, about half of the interviewed patients
      (47.5%) showed mainly positive feelings due to the prospect of treatment and
      cure. Our results suggest that misdiagnoses and unawareness of the disease were
      the main factors that influenced the delayed diagnosis. We consider the effective
      involvement of various segments of society, particularly the integration and
      partnership of the public health services and health education centres to be
      valuable tools for the planning and execution of educational activities directed
      at risk groups and the community.

PMID- 14577471
TI  - Field treatment of leprosy reactions in Northern Nigeria: feasibility, including
      the use of prednisolone in blister packs.

PMID- 14577472
TI  - Comparison between anti-PGL-I serology and Mitsuda reaction: clinical reading,
      microscopic findings and immunohistochemical analysis.
AB  - The lepromin test, serum IgM antibodies against Mycobacterium leprae and in situ
      observations of T cell subsets in biopsies of Mitsuda reaction using monoclonal
      antibodies were performed on 44 untreated leprosy patients belonging to various
      classifications of the disease. The Mitsuda reaction was accessed clinically and
      histologically after 28 days. Clinical reading and histological analysis of
      Mitsuda reaction showed good agreement. The high positivity in clinical reading
      correlated with compact granulomas in histology. There is a graduation of Mitsuda
      reaction that follows the immunological spectrum of the disease. The histological
      study of Mitsuda reaction is valuable to confirm the immunological condition in
      doubtful clinical reaction. Anti-PGL-I IgM levels correlated with disease
      classification, increasing from the tuberculoid towards the lepromatous pole of
      the disease spectrum. There was an inverse correlation between serum IgM antibody
      levels and clinical and histological reading of Mitsuda reaction. There were no
      statistical difference in quantities and distribution of CD4+ and CD8+ T cells in
      all Mitsuda reactions. The pattern of cellular content of Mitsuda reaction could
      not be related to the T cells.

PMID- 14577473
TI  - Generalized anetoderma in a patient with HIV and dual mycobacterial infection.
AB  - A middle-aged HIV infected man receiving treatment for pulmonary tuberculosis,
      presented with a febrile illness along with evanescent, erythematous nodular
      lesions all over the body. On examination, he had features suggestive of
      lepromatous leprosy with lesions of erythema nodosum leprosum. In addition, there
      were multiple small, circumscribed areas of slack skin, clinically and
      histopathologically suggestive of anetoderma. Both leprosy and HIV infection are
      known to give rise to lesions of anetoderma. Pathogenesis of anetoderma in these
      infectious conditions is discussed.

PMID- 14577474
TI  - Leprosy: from the clinics of a tertiary institution in South Eastern Nigeria.

PMID- 14577476
TI  - Patient and health services delay in the diagnosis of leprosy in Kaduna State,
      Nigeria.

PMID- 14577475
TI  - Begging as a profession and dehabilitation among leprosy patients.

PMID- 14577477
TI  - The return of thalidomide: new uses and renewed concerns.

PMID- 14577478
TI  - On thalidomide and WHO policies.

PMID- 14577479
TI  - The return of thalidomide: new uses and renewed concerns--reply.

PMID- 14577480
TI  - The return of thalidomide: new uses and renewed concerns--reply.

PMID- 14577481
TI  - Psycho-social well-being and general health status after surgical treatment for
      localized renal cell carcinoma.
AB  - OBJECTIVE: To comparatively assess the psychological, social well-being and
      general state of health in patients with stage 1 renal cell carcinoma (RCC)
      (according to 1997 TNM), who underwent either elective nephron sparing surgery
      (NSS) or radical nephrectomy. PATIENTS AND METHODS: We evaluated the health
      related quality of life (HR-QoL) in 88 patients who underwent radical nephrectomy
      and in 56 treated with elective NSS. The measurement of the main QoL components
      has been made using domain-specific questionnaires tested and validated in
      Italian language. Each questionnaire has been self-administrated during follow-up
      (cross-sectional study). RESULTS: The two analysed group resulted perfectly
      comparable regarding age, gender, civil status, educational level, profession and
      mean follow-up. A low level anxiety has been documented in 11.4% of patients
      after radical nephrectomy and in 1.8% of those treated with an elective
      conservative surgery. The mean score difference between the two groups resulted
      statistically significant (p = 0.003). A mild depression has been recorded in 7%
      of patients who underwent radical nephrectomy and in 2.3% of NSS group. The mean
      score difference between the two groups was statistically significant (p = 0.01).
      The general health status was impaired in 12.5% of cases after radical
      nephrectomy and in 7% after elective NSS. Social problems were present in 18% of
      patients who underwent radical nephrectomy and in 18% of NSS group. There was no
      significant difference between radical and conservative group in terms of both
      General health Questionnaire and Social Problem Questionnaire mean scores.
      CONCLUSION: HR-QoL in patients who underwent surgery for RCC is not particularly
      negatively affected. Nevertheless, the comparative analysis of the results showed
      that, at a long term follow-up, radical surgery seems to eventually cause a more
      relevant negative impact on the psychological well-being than conservative
      surgery.

PMID- 14577482
TI  - Synergism between the brushite and hydroxyapatite urinary crystallization
      inhibitors.
AB  - The aim of this paper is to study possible synergic effects between
      crystallization-inhibitor molecules of low molecular weight on the hydroxyapatite
      and brushite crystal nucleation. Kinetic-turbidimetric measurements were
      performed to follow the nucleation process in synthetic urine at 37 degrees C.
      Only pyrophosphate + phytate mixture manifested synergic effects on the brushite
      nucleation, whereas the mixture pyrophosphate + citrate exhibited synergic
      effects only on the hydroxyapatite nucleation. It seems clear that synergic
      effects between the crystallization inhibitory capacity of some substances in
      urine can take place and as a consequence, the high crystallization inhibitory
      capacity of healthy urine could be assigned not only to the individual inhibitory
      capacity of each product but also to the synergic effects between different
      products.

PMID- 14577483
TI  - Percutaneous endopyelotomy for ureteropelvic junction obstruction.
AB  - Percutaneous endopyelotomy was performed 13 times on 11 patients with primary and
      secondary UPJ obstruction between 1994 and 2002. Excretory urogram revealed
      improvement in ten of eleven patients. One of the ten successfully treated
      patients required repeated endopyelotomy. Endopyelotomy failed in one patient,
      who had secondary UPJ obstruction that had been stenosed by granuloma caused by a
      ureteral stone. As the patient had UPJ obstruction of high insertion type with
      thinned renal parenchyma, nephrectomy was performed after repeated endopyelotomy.
      Compared with open pyeloplasty, percutaneous endopyelotomy is less invasive and
      is cosmetically advantageous.

PMID- 14577484
TI  - Extracorporeal shock wave lithotripsy for cystine urolithiasis in children:
      outcome and complications.
AB  - The Siemens Lithostar Litotriptor was used to treat 6 children with cystine
      nephrolithiasis, previously treated by open surgery. Five children had renal
      calculi (3 multiple caliceal, 2 pelvis) and one had ureteral calculus. Stone size
      ranged from 0.2-2.5 cm in diameter, and stone burden was from 0.24 to 10.81 cm3
      per kidney. From one to 4 ESWL sessions per unit were applied, with a total of
      1,800 to 12,000 shock waves. The stone free rate at 3 months was 50%. A complete
      elimination was obtained with cystine stones in renal pelvis and ureter, however,
      up to 4 ESWL treatments failed in caliceal stones. Rather location of cystine
      calculi than previous surgery was associated with ESWL success rate. Two patients
      with positive urine cultures were successfully treated with appropriate
      antibiotics before ESWL was attempted. Perirenal hematoma was major complication
      demonstrated by radionuclide scintigraphy in one patient, and resolved
      spontaneously by 3 months. In the combined treatment of cystine urolithiasis in
      children ESWL, as auxillary procedure, was safe and effective in pelvis stone but
      failed in caliceal stones. Medical dissolution for retained fragments was found
      effective.

PMID- 14577485
TI  - Holmium: YAG laser rescue for a stuck stone basket.
AB  - A 35-year-old man with left lower ureteric stone underwent ureteroscopic stone
      removal. Holmium: YAG laser lithotripsy was used to break the stone and to remove
      a larger fragment a 3 Fr. steel wire stone basket was introduced through the
      ureteroscope. However, during removal the basket with the stone became impacted
      in the intramural part of the ureter. All attempts to dislodge the stone and the
      basket failed. Laser fiber was introduced through the second channel of the
      ureteroscope bridge and the laser activated at settings of 0.5J and 10Hz.
      Pulverization of the stone did not free the basket and hence 2 wires of the stuck
      basket were cut with the laser. This enabled the basket to be freed and easily
      removed.

PMID- 14577486
TI  - A rare co-existence of focal xanthogranulomatous pyelonepheritis, angiomyolipoma
      and renal cysts simulating renal cell carcinoma.
AB  - A 70-year-old male presented with left flank pain and history of gross, total
      painless haematuria of 6 months duration. Investigations revealed a large solid
      and cystic mass suggestive of renal cell carcinoma in left kidney with possible
      infiltration of left psoas muscle. Histology of radical nephrectomy showed
      angiomyolipoma with multiple cysts lined by columnar epithelium suggestive of
      tuberous sclerosis and focal area of xanthogranulomatous pyelonepheritis. The
      rare combination of such lesions leading to diagnostic dilemma has not been
      reported in medical literature to the best of our knowledge.

PMID- 14577487
TI  - Fluid volume compartments and biochemical measurements for disclosing fluid
      depletion during acute and rigorous bed rest in normal subjects.
AB  - Rigorous bed rest (RBR) induces fluid depletion, however, little is known about
      the mechanisms of development of fluid depletion during acute bed rest (ABR).
      Measuring fluid retention and body hydration parameters, the aim of this study
      was to establish whether ABR than RBR could depress significantly more fluid
      retention contributing to greater fluid depletion development. Studies were
      conducted during pre bed rest (BR) period of three days and during seven days
      period of ABR and RBR. Thirty normal male individuals aged, 24.2 +/- 5.0 years
      chosen as subjects. They were divided into three groups: unrestricted ambulatory
      control subjects (UACS), acute bed rested subjects (ABRS) and rigorous bed rested
      subjects (RBRS). Acute bed rested subjects confined abruptly to RBR, while they
      did not have any prior knowledge of the exact date and time when they would be
      asked to stay in bed. Rigorous bed rested subjects submitted to RBR on a
      predetermined date and time known to them right from the start of the study.
      Unrestricted ambulatory control subjects were not confined to any type of bed
      rest. Fluid loss, urinary and plasma sodium (Na+) and potassium (K+), urinary
      osmolality and plasma osmolality, whole blood hematocrit (Hct), whole blood
      hemoglobin (Hb), and total plasma protein increased significantly (p < 0.05) with
      time, while fluid retention, extracellular volume (ECV), plasma volume (PV), red
      cell volume (RCV), blood volume (BV), interstitial volume (IV) and fluid intakes
      reduced significantly (p < 0.05) with time in ABRS and RBRS compared with their
      pre-BR values and the control values (UACS). However, the measured parameters
      changed significantly (p < 0.05) more with time in ABRS than RBRS. Fluid rention,
      fluid loss, fluid intake, urinary and plasma Na+ and K+, Hct, Hb, plasma protein,
      urinary and plasma osmolality, ECV, PV, RCV, BV and IV did not change in UACS
      compared with their pre-BR values. It was concluded that significant increase of
      urinary and plasma osmolality, whole blood Hct and Hb, total plasma protein,
      plasma Na+ and K+, and significant decrease of ECV, PV, RCV, BV, and IV may
      demonstrate fluid depleteion, while a higher increase of fluid loss in spite of
      fluid depletion may show decreased fluid retention. Dissociation between fluid
      losses and fluid depletion may suggest the presence of impair fluid retention as
      a mechanism of development of fluid depletion.

PMID- 14577488
TI  - The prevalence and pattern of congenital anomalies of the urinary tract detected
      by intravenous urography in Kuwait.
AB  - We conducted a prospective population-based study in Kuwait to determine the
      prevalence and pattern of previously undiagnosed congenital anomalies of urinary
      tract in patients undergoing intravenous urography (IVU) and to examine the
      demographic factors associated with these anomalies. The study included 2398
      consecutive patients undergoing IVU, for various indications, in all the six
      public hospitals in Kuwait, during the period 1 June 1999-30 September 2000.
      Patients were also interviewed to obtain selected demographic information.
      Multiple logistic regression was used to identify factors associated with the
      anomalies. The average age (+/- SD) of the patients (1623 males, 775 females) was
      39.2 +/- 15.1 years. A total of 335 anomalies (12.1% in males, 17.9% in females;
      p < 0.001) were detected in 300 (12.5%) patients (10.9% males, 15.9% females; p <
      0.01). About half (47.2%) of the anomalies involved the kidney, 28.4% renal
      pelvis, 22.4% ureters, and 2.1% bladder. Multiple regression analysis showed that
      age < 20 years (odds ratio (OR) = 12.5; 95% confidence interval (95% CI): 7.0
      22.3) female gender (OR = 1.5; 95% CI: 1.2-2.0) Kuwaiti nationality (OR = 1.7;
      95% CI: 1.2-2.3) and family history of congenital malformation (OR = 3.8; 95% CI:
      2.2-6.6) were independently associated with the anomalies of the urinary tract.
      Overall, 42% of the patients reported a consanguineous marriage between their
      parents. The frequency of anomalies was higher in individuals who had
      consanguineous parents (13.8 vs. 11.6%; OR = 1.2) but this positive association
      did not reach statistical significance. Considering the relatively high
      prevalence of previously undiagnosed congenital anomalies of the urinary tract,
      it is important to establish clinical guidelines for early detection and
      management of these conditions to decrease the associated morbidity and
      mortality.

PMID- 14577489
TI  - Radiopaque shadow in the lumbar region on plain X-ray abdomen: diagnostic
      dilemma.
AB  - A 28-year-old man presented with right flank pain. Radiological investigations
      suggested the diagnosis of a calcified mass in the retroperitoneum below the
      right kidney. Laparoscopic exploration using the retroperitoneoscopic approach
      was performed. However, it was not possible to locate the lesion and an open
      exploration was done. During exploration a large fecolith was found trapped in a
      diverticulum of the cecum.

PMID- 14577490
TI  - Genitourinary fistulas of obstetric origin.
AB  - OBJECTIVE: To review the results of management of 42 cases of genitourinary
      fistulas of obstetric origin. SETTINGS: Department of urology, Nishtar Hospital,
      Multan, Pakistan. METHODS: Forty two cases of genitourinary fistulas (36
      vesicovaginal, 2 vesicouterine, one ureterovaginal and 3 urethrovaginal) were
      repaired from 1st December, 1999 to 31st May, 2002). All fistulas were repaired
      three months or more after formation. Trans-abdominal and vaginal repair of
      vesicovaginal fistulas was undertaken in 29 and 7 patients respectively. Two
      patients had trans-abdominal closure of vesicouterine fistulas.
      Ureteroneocystostomy with antireflux mechanism was performed for uretereovaginal
      fistula. For three urethrovaginal fistulas transvaginal layered repair was
      carried out. RESULTS: Overall success rate for all types of fistula was 85.7% (36
      pts). CONCLUSION: The surgical treatment of genitourinary fistulas will depend
      upon the type, size and location of fistula. Acceptable results can be achieved
      by adhering to the surgical principles of fistula repair i.e. optimal tissue
      conditions, adequate exposure and tension free closure.

PMID- 14577491
TI  - The expression of PAX5, p53 immunohistochemistry and p53 mutation analysis in
      superficial bladder carcinoma tissue. Correlation with pathological findings and
      clinical outcome.
AB  - OBJECTIVES: The expression pattern of PAX5 in the tissue of superficial bladder
      transitional cell carcinoma (TCC), its prognostic value and its correlation with
      p53 immunohistochemistry and p53 mutation analysis were evaluated. METHODS: Study
      comprised 61 patients with histologically confirmed superficial bladder TCC.
      Expression level of PAX5 mRNA was investigated using reverse transcriptase
      polymerase chain reaction (RT-PCR) and determined semiquantitatively. The
      presence of p53 mutations was determined by SSCP and confirmed by direct
      sequencing. The p53 immunohistochemistry was performed with DO1 antibody and
      semiquantitatively evaluated using HSCORE (HS) method. As the control group for
      the evaluation of the PAX5 expression served 8 men with benign prostatic
      hyperplasia. RESULTS: PAX5 expression was found in 50 patients with bladder TCC
      but in no patient from the control group. Its quantity however correlated neither
      with the stage nor with the grade of the tumor. P53 mutation was confirmed only
      in 1 patient with pTaG2 tumor in exon 5 (deletion of proline 128). On the
      contrary, positive immunohistochemical staining of p53 was detected in most
      patients. Using the cutoff value of HS 200, 56.9% of patients showed p53
      overexpression. Quantity of p53 immunochistochemical positivity did not correlate
      with the quantity of PAX5 expression. Using the cutoff values of HS 200 for p53
      and of 0.2 for PAX5, 7 of 8 patients with future progression had p53 and 4 had
      PAX5 overexpression respectively. CONCLUSION: The expression of gene PAX5 is a
      frequent event in superficial TCC of the bladder.

PMID- 14577493
TI  - Xanthoma of urinary bladder.

PMID- 14577492
TI  - Screening for prostate cancer in Romania.
AB  - In Romania, more than 95% of patients present with advanced stage prostate cancer
      at the time of diagnosis. Our purpose was to detect early prostate cancer in the
      Romanian city of Oradea, with a screening based on digital rectal examination and
      fine needle aspiration biopsy. We performed digital rectal examinations on 701
      men, between 50 to 80 years of age. Four men with a history of prostate cancer
      were excluded from the study. Transrectal fine-needle aspiration biopsies were
      done in 15 men who presented with suspicious findings at the digital rectal
      examination. Prostate cancer was cytologically proven in eleven men. Nine of
      these were low- to intermediate grade (GI-II) and clinically localized (T2). Two
      patients had clinical stage T3 tumors. The prostate cancer detection rate in the
      screened population was 1.6% (11/697). Currently, eight men have undergone total
      retropubic prostatectomy. One patient presented with pelvic lymph node metastases
      and, after a staging lymphadenectomy, only a bilateral orchiectomy was performed.
      This first Romanian mass screening study for prostate cancer revealed a great
      interest in early cancer detection among the general public. Continued effort to
      make asymptomatic men aware of the disease may ultimately lead to an overall
      stage reduction at the time of diagnosis in Romania.

PMID- 14577494
TI  - Urethral recurrence after sigmoid orthotopic neobladder. What should be the ideal
      treatment approach?
AB  - Orthotopic neobladder reconstruction has become a standard procedure in patients
      undergoing radical cystectomy for invasive bladder cancer. In addition the known
      sequelae like nocturnal enuresis, need of self-intermittent catherisation and
      stricture at urethro or ureteroileal anastomosis, one of the most unfortunate
      event to happen is the recurrence of malignancy that may require the removal of
      the neobladder lessening the quality of life suddenly. There is a little
      information about the cases of urethral recurrence of transitional cell carcinoma
      of the bladder after cystectomy and orthotopic neobladder. We report such a case
      and management dilemma as the patient is young and does not want to loose body
      image and a brief review of literature is presented.

PMID- 14577495
TI  - Quality and cost between transcervical and transurethral prostatectomy.
AB  - Although transurethral resection of the benign prostate (TURP) is a popular
      technique, it is not without problems. The average postoperative morbidity could
      be up to 50%. Therefore the quality of life and the total cost have been
      evaluated in this study, since the incidence of re-TURP was reported to be as
      high as 25% in 8 years period. This was attributable to incomplete resection, in
      that only about 40% of the prostatic tissue being resected by this technique. In
      contrast, transcervical prostatectomy (TCP) performs a total enucleation of the
      gland. It seems to be cost effective, in that the postoperative urethral catheter
      is removed routinely on the second day and the patients are discharged home on
      the fourth day routinely. The total incidence of morbidity, by contrast, was less
      than 5% and that of mortality under 1%. The initial cost for the primary
      operation would not be much difference between the these two techniques, but the
      average cumulative cost per TURP would be expensive, if all the expenses incurred
      for the treatment of postoperative complications are added together. It would be
      between pounds sterling 2574.00 and pounds sterling 2434.00, for the primary
      operation. But the cumulative cost for TURP would be pounds sterling 4333.00 and
      for TCP pounds sterling 2580.00. The true cost for the operation of TURP could be
      as high as pounds sterling 10720, compared to pounds sterling 2434.00, being the
      operation charge for TCP, if all expenses have to be paid by the patient.
      CONCLUSION: Transcervical Prostatectomy compares favourably with TURP in every
      aspect, apart from the skin cut in the lower abdomen.

PMID- 14577496
TI  - The free-to-total serum prostatic specific antigen ratio as a predictor of the
      pathological features of prostate cancer.
AB  - OBJECTIVES: Curative therapy and extended period of disease free survival for
      patients with prostate cancer is possible only if the radical prostatectomy is
      performed when the disease is organ confined. It has been shown that combined use
      of local clinical stage, Gleason score of transrectal needle biopsy and serum PSA
      can accurately predict the final pathological stage in men undergoing radical
      prostatectomy. Recently the free/total PSA (F/T PSA) has been shown to improve
      the specificity of serum PSA level in early detection prostate cancer. In this
      study the utility of F/T PSA ratio in prediction the final pathological features
      of the prostate cancer was investigated. METHODS: 52 patients who had undergone
      radical prostatectomy were included in this study with mean age of 63 (ranging
      from 49 to 73). According to the pathologic features of the tumors, patients were
      classified as organ confined in 37 (%71), specimen-confined in 39 (%75) and as
      with favorable pathology which was defined as organ confined or specimen confined
      with Gleason score lower than 7, 39 (%75) patients. RESULTS: Neither total PSA
      levels nor F/T PSA values correlate significantly with the pathological
      characteristics of the tumor. The logistic regression analysis showed that the
      biopsy Gleason score was the only variable that was able to predict the pathology
      of the tumor (p < 0,05). CONCLUSION: As a conclusion Gleason score of the needle
      biopsy specimen is the most predictive factor of the final pathological outcome.
      F/T PSA ratio did not provide additional information about predicting
      pathological stage.

PMID- 14577497
TI  - Ectopic prostate: an unusual bladder tumor.
AB  - A 25-year-old man presented with gross painless hematuria. Cystoscopy revealed a
      smooth surfaced mass in the supratrigonal region. Complete transurethral
      resection of the mass was done. Histopathological examination revealed benign
      prostatic tissue situated ectopically.

PMID- 14577498
TI  - Echinococcal cyst of the seminal vesicles: a case-report and literature review.
AB  - Solitary echinococcal cysts of the seminal vesicles are very uncommon. The use of
      ultrasonography, computed tomography and magnetic resonance imaging aids
      considerably in the differential diagnosis. Surgical removal of pelvic
      echinococcal cysts should be performed with great caution to avoid accidental
      puncture and parasite spillage in the retroperitoneal space. We report on a case
      of a male patient presenting with urinary retention owing to a large hydatid cyst
      of the seminal vesicles. The literature regarding this rare clinical entity is
      also reviewed.

PMID- 14577499
TI  - Primary embryonal rhabdomyosarcoma of prostate in adults: diagnosis and
      management.
AB  - Embryonal rhabdomyosarcoma of the prostate is a common tumour in infants and
      children. It is rarely seen in adults. The combined modality has improved outcome
      in children, where as in adults prognosis is poor. The lack of awareness of this
      entity in adults, delay in diagnosis and a more aggressive behavior of this
      malignancy are some of the reasons. We report two cases of embroyonal
      rhabdomyosarcoma of prostate in adults along with review of literature with an
      aim to define natural history and formulate treatment policy.

PMID- 14577500
TI  - Tubularized incised plate urethroplasty for distal hypospadia, using overlapping
      dorsal subcutaneous flaps.
AB  - This paper presents a newly developed simple procedure using overlapping
      vascularized dorsal dartos subcutaneous flaps to cover the neourethra after
      hypospadias correction. A 3-year old boy with distal hypospadias underwent the
      tubularized incised plate urethroplasty using this method. Postoperative
      complications, which include urethrocutaneous fistula, were not observed, but the
      glans did exhibit a vertical, slit-like meatus. Covering the neourethra with
      overlapping dorsal dartos flaps is expected to prevent the development of
      urethrocutaneous fistula in patients with distal hypospadias.

PMID- 14577501
TI  - Electrourethrogram: study of the electric activity of the urethra and its
      clinical significance.
AB  - PURPOSE: Apart from the urethral sphincters, the electric activity of the urethra
      has not been fully addressed in the literature. We investigated the hypothesis
      that also the non-sphincteric part of the urethra possesses electric activity
      which may have clinical significance. MATERIALS AND METHODS: Urethral electric
      activity was studied in 24 healthy volunteers (mean age 40.6 +/- 13.6 years, 14
      women). Two electrodes in women and three in men were applied to the urethral
      mucosa distal to the striated urethral sphincter. A manometric catheter was
      placed into the penile urethra in men and distal to the striated sphincter in
      women. RESULTS: Monophasic negatively deflected slow waves were recorded. Their
      frequency, amplitude and conduction velocity were identical in the electrodes of
      the individual subject and were reproducible. The slow waves were followed or
      superimposed by fast activity spikes or action potentials which occurred randomly
      and were associated with urethral pressure rise. The pattern of electric activity
      was stable in the same subject on all test sessions. CONCLUSIONS: A normal
      electrourethrogram could be identified. It consisted of slow waves and action
      potentials. The waves had a regular rhythm. The action potentials appear to have
      a motor activity and are suggested to clear the urethra of the residual urine and
      secretions that may exist in the urethra after micturition. The clinical
      significance and diagnostic role of the electrourethrogram need to be further
      investigated.

PMID- 14577502
TI  - Changes in serum sodium, sodium balance, water balance, and plasma hormone levels
      as the result of pelvic surgery in women.
AB  - Postoperative hyponatremia in women has been associated with the development of
      serious neurological disorders and even death, with a predisposition for
      menstruant women. The objective of this study was to evaluate the immediate
      hormonal, water and electrolyte responses to pelvic surgery in both pre and
      postmenopausal women. Of the twenty-five consecutive women studied, twenty were
      premenopausal while five were postmenopausal. Mean age was 45.4 +/- 1.6 years.
      Measurements of plasma renin activity, follicular stimulating hormone and
      luteinizing hormone showed no significant change pre to postoperatively. There
      was a significant decrease in pre to postoperative values of estrogen, 97.4 +/-
      20.3 to 36.3 +/- 7.5 pg/mL (p < 0.05). There was also a significant decline in
      postoperative values for plasma aldosterone and plasma progesterone. Data were
      similar in pre and postmenopausal patients. Serum sodium levels decreased from
      141.5 +/- 0.5 to 137.2 +/- 0.5 mEq/L (p < 0.01). During the twenty-four hours
      following surgery, mean net sodium balance was positive 122 mEq and mean measured
      fluid balance was positive 1108 mL. Ringers lactate or normal saline were used.
      On the first postoperative day, plasma arginine vasopressin levels were elevated
      at 4.0 +/- 0.8 pg/mL, with a mean urine osmolality of 504 +/- 29 mOsm/kg H2O. The
      data illustrate that women undergoing pelvic surgery decrease their serum sodium
      in the immediate postoperative period. Despite both positive sodium and water
      balance, there is a stronger tendency to conserve water. Decreased estrogen
      levels occur and this decrease may facilitate brain cell adaptation to plasma
      hypotonicity. Since the administration of isotonic fluid will not protect against
      the decrease in serum sodium, postoperative sodium concentration should be
      carefully monitored.

PMID- 14577503
TI  - Tuberculosis in renal transplant recipients: rifampicin sparing treatment
      protocol.
AB  - The reactivation of mycobacterium infection in renal transplant recipients in
      developing countries is a common therapeutic dilemma, especially in those
      patients receiving cyclosporin immunosuppression. The inclusion of rifampicin in
      the antituberculosis protocol increases the risk of precipitating acute allograft
      rejection due to its interaction with cyclosporin and also increases the
      financial burden. We successfully treated 16 patients who developed mycobacterial
      infection post renal transplant with a rifampicin sparing antituberculosis drug
      regimen. Pyrexia of unknown origin was the most common manifestation observed and
      a therapeutic trial with antituberculosis drugs is justified. De novo diabetes
      mellitus appears to be an added risk factor and increases the susceptibility to
      mycobacterial infection.

PMID- 14577504
TI  - Down regulation of CD45 expression on CD4 T cells during acute renal allograft
      rejection: evidence of a decline in T suppressor/inducer activity.
AB  - Acute rejection is associated with the activation of helper and cytotoxic cells.
      A shifting balance between the suppressor/inducer CD45+ CD4+ and T helper/inducer
      (CD4+CD45-) cells may be responsible for the transition from quiescence to overt
      rejection. We examined the kinetics of CD45 expression on CD4+ T cells in renal
      allograft recipients from pretransplant values to acute rejection and after
      reversal of rejection, searching for a shift in balance between helper/inducer
      and suppressor/inducer cell subsets. Using two color flow cytometry, the
      peripheral blood levels of CD4+, CD4+CD45- [T helper/inducer (Thi)], CD4+CD45+ [T
      suppressor/inducer (Tsi)], CD3+, and CD8+ T cells subsets and their
      interrelationships, were determined in 49 patients prior to transplantation, and
      in 10 of them, during acute rejection and after its reversal. Results were
      analyzed and compared to data obtained from 10 healthy blood donors. Acute
      rejection was associated with a significant decline in CD45+ CD4+ expression
      compared to quiescent phase (22% +/- 3.7% vs. 26.5% +/- 3.2%, p = 0.05) and
      controls (29.5% +/- 6.2%, p = 0.01). No difference was observed compared to
      pretransplant levels (19.9% +/- 3.2%, p = ns). CD45-/CD45+ (Thi/Tsi) ratio was
      lowest during quiescence (0.75) compared to rejection (0.97, p = 0.05), in
      controls (0.98, p = 0.05) and pretransplant values (1.4, p = 0.01). Acute
      rejection was characterized by higher Thi/CD8+ and lower Tsi/CD8+ ratio (103 and
      88 respectively, p = 0.045), compared to clinical quiescence (104 and 116
      respectively, p = 0.039). These data suggest that acute rejection is associated
      with down regulation of CD4+CD45+ suppressor/inducer subset. This shift may
      account for the transition from quiescence to overt rejection, concurring with
      reports on CD4+CD45 regulatory function.

PMID- 14577505
TI  - Wegener's granulomatosis diagnosed by testicular biopsy.
AB  - Urogenital involvement, other than the kidneys, is extremely rare in Wegener's
      granulomatosis (WG) and occurs in less than 1% of the cases. When encountered it
      is confined to prostate, bladder, urethra, cervix, and vagina. Granulomatous
      infiltration of the testis from WG has not been cited in the medical literature.
      We report a case of WG in a Hispanic male who presented with sensorineural
      hearing loss and hemoptysis. He had a pulmonary lesion and a painless right
      testicular mass, which was found to have necrotizing granulomas on excisional
      biopsy. This may be the first reported case of WG diagnosed by testicular biopsy
      as testicular involvement is rare in WG. We believe that the actual incidence of
      testicular involvement in WG may be higher as genital examination may be ignored
      during routine physical examinations.

PMID- 14577506
TI  - Possible factors contributing to similar peritoneal dialysis outcome in patients
      over 60 years of age and the younger ones.
AB  - The aim of studies was a comparison of dialysis adequacy, nutritional parameters,
      results of the peritoneal equilibration test (PET) and selected standard clinical
      and laboratory data in peritoneal dialysis (PD) patients with different age, but
      comparable PD duration and outcome. Two groups of patients were examined: group I
      (n = 21, 9 F, 12 M) - age 67.7 +/- 4.5 yrs, PD duration 20.1 +/- 12.1 months;
      group II (n = 21, 9 F, 12 M) - age 42.8 +/- 9.1 yrs, PD duration 20.7 +/- 12.1
      months. Parameters of PD adequacy, results of PET, markers of nutrition and
      standard laboratory measures were determined every 3 months to the end of PD
      treatment. First obtained values, mean values representing the entire PD course
      and last values obtained before the end of PD therapy were compared in group I
      and II. Differences in results obtained at the beginning and at the end of PD
      therapy were also compared in each group. At the beginning of PD therapy the
      older patients showed higher total fat mass (TFM) expressed as % of total body
      mass (TBM), lower lean body mass (LBM), lower serum levels of iron, phosphorus
      and creatinine as well as lower transferrin saturation. When mean values
      representing the entire PD course were compared, the older patients showed higher
      TFM as % of TBM and serum ferritin level, whereas lower values were observed for
      diastolic blood pressure (DBP), LBM, serum creatinine, phosphorus and iron. At
      the end of PD therapy TFM as % of TBM and serum ferritin level remained higher in
      older patients as well as lower both DBP and LBM were maintained. Additionally,
      serum cholesterol level and residual renal function (RRF) became at the end of PD
      treatment higher in the older individuals compared to the younger ones. The
      difference in RRF between the two groups was caused by the decline in RRF in the
      younger patients with relatively stable values of RRF in the older ones.
      Nutritional parameters improved in the course of PD only in the younger group. In
      conclusion, the older patients reach similar PD outcome parameters compared to
      the younger ones while they show higher TFM as % of TBM, stable RRF and more
      satisfactory DBP. However, elderly patients show a greater progress in the
      deterioration of indices of both inflammation and atherosclerosis and therefore
      are not able to improve nutritional parameters.

PMID- 14577507
TI  - The very elderly dialysis patient: indication and discontinuation of dialysis.
AB  - 1. When the current available data in the literature is summarized it becomes
      evident that the majority of it supports the position that it is, at least for
      medical reasons, not advisable to exclude patients over the age of 80 years from
      chronic dialysis. 2. It is correct to say that the refusal of dialysis therapy
      for elderly dialysis patients would lead to a not insignificant cutting of costs,
      although elderly patients are not as 'expensive' as younger dialysis patients. 3.
      The decision to exclude patients over 80 from dialysis treatment is difficult, in
      our opinion, to support ethically. 4. The refusal of therapy by a dialysis
      patient--independent of his age--can only occur with his/her consent, as long as
      the patient is clearly conscious of the decision. 5. Should the patient no longer
      be in the condition to exercise his/her autonomy, and there is no AD, the
      Surrogate's Court must be consulted. 6. AD can be seen as helpful, since they not
      only make the decisions for physicians easier, but also because they can be seen
      as an act of care for family members. 7. Whenever dialysis therapy is
      discontinued the problematic nature of so-called essential care should be
      carefully considered, especially if no clear position has been taken in an AD.

PMID- 14577508
TI  - A case report of tubulo-interstitial nephritis with uveitis (TINU syndrome) and
      follow-up for one year.

PMID- 14577509
TI  - Geriatric nephrology and urology literature.

PMID- 14577510
TI  - Pioneers in cholesterol research capture America's top award in medicine.

PMID- 14577511
TI  - Bristol-Myers Squibb announces Distinguished Achievement Awards and unrestricted
      biomedical grant recipients.

PMID- 14577512
TI  - Charles C. J. Carpenter receives John E. Fogarty Recognition Award for
      international health.

PMID- 14577513
TI  - Gairdner Foundation recognizes achievement in medical research.

PMID- 14577514
TI  - National Academy of Sciences honors Carol W. Greider with the Richard Lounsbery
      Award.

PMID- 14577515
TI  - Protection of human research subjects.

PMID- 14577516
TI  - Unresolved issues stall approval of Project Bioshield.

PMID- 14577517
TI  - Molecular mechanisms, diagnosis, and rational approaches to management of and
      therapy for Charcot-Marie-Tooth disease and related peripheral neuropathies.
AB  - During the last decade, 18 genes and 11 additional loci harboring candidate genes
      have been associated with Charcot-Marie-Tooth disease (CMT) and related
      peripheral neuropathies. Ten of these 18 genes have been identified in the last 2
      years. This phenomenal pace of CMT gene discovery has fomented an unprecedented
      explosion of information regarding peripheral nerve biology and its pathologic
      manifestations in CMT. This review integrates molecular genetics with the
      clinical phenotypes and provides a flowchart for molecular-based diagnostics. In
      addition, we discuss rational approaches to molecular therapeutics, including
      novel biologic molecules (eg, small interfering ribonucleic acid [siRNA],
      antisense RNA, and ribozymes) that potentially could be used as drugs in the
      future. These may be applicable in attempts to normalize gene expression in cases
      of CMT type 1A, wherein a 1.5 Mb genomic duplication causes an increase in gene
      dosage that is associated with the majority of CMT cases. Aggresome formation by
      the PMP22 gene product, the disease-associated gene in the duplication cases,
      could thus be avoided. We also discuss alternative therapeutics, in light of
      other neurodegenerative disorders, to disrupt such aggresomes. Finally, we review
      rational therapeutic approaches, including the use of antioxidants such as
      vitamin E, coenzyme Q10, or lipoic acid to relax potential oxidative stress in
      peripheral nerves, for CMT management.

PMID- 14577518
TI  - Antioxidant potential and transferrin, ceruloplasmin, and lipid peroxidation
      levels in women with preeclampsia.
AB  - BACKGROUND: The aim of this study was to evaluate lipid peroxidation and
      antioxidant function in patients with preeclampsia and in normotensive pregnant
      women and to assess an association with the severity of the disease. METHODS:
      Twenty-one patients with mild preeclampsia, 15 patients with severe preeclampsia,
      and 19 normotensive pregnant women were included in the study. Plasma antioxidant
      potential (AOP) status, ceruloplasmin (Cp) and transferrin (Trf) levels as
      antioxidants, and malondialdehyde (MDA) levels as an indicator of lipid
      peroxidation were measured. RESULTS: Whereas the AOP and Trf levels of the severe
      and mild preeclampsia groups were found to be reduced, the MDA and Cp levels were
      increased compared with those of the normotensive pregnant group. There were
      statistically significant negative correlations between AOP and MDA in all
      groups. No differences were observed between the groups with severe and mild
      preeclampsia with respect to these analytes. CONCLUSION: Our findings suggest
      that lipid peroxidation may be an important factor in the pathogenesis of
      preeclampsia and that plasma antioxidants and oxidants are altered in
      preeclampsia. However, these findings may not be useful in distinguishing women
      with severe and mild preeclampsia.

PMID- 14577519
TI  - Perinatal asphyxia exerts lifelong effects on neuronal responsiveness to stress
      in specific brain regions in the rat.
AB  - BACKGROUND: Perinatal asphyxia (PA) causes irreversible damage to the brain of
      newborns and can produce neurologic and behavioral changes later in life. To
      identify neuronal substrates underlying the effects of PA, we investigated
      whether and how neuronal responsiveness to an established stress challenge is
      affected. METHODS: We used Fos expression as a marker of neuronal activation and
      examined the pattern of Fos expression in response to acute swim stress in 24
      month-old rats exposed to a 20-minute PA insult. RESULTS: Swim stress produced a
      similar pattern of Fos expression in control and asphyxiated rats in 34 brain
      areas. Asphyxiated rats displayed a higher number of stress-induced Fos-positive
      cells in the nucleus of the solitary tract, parabrachial nucleus, periaqueductal
      gray, paraventricular hypothalamic nucleus, nucleus accumbens, caudate-putamen,
      and prelimbic cortex. No differences in the Fos response to stress were observed
      in other regions, including the locus ceruleus, amygdala, hippocampus, or septum.
      CONCLUSION: These data provide functional anatomic evidence that PA has lifelong
      effects on neuronal communication and leads to an abnormal, augmented neuronal
      responsiveness to stress in specific brain areas, particularly in the main
      telencephalic target regions of the mesencephalic dopamine projections, as well
      as in a functionally related set of brain regions associated with autonomic and
      neuroendocrine regulation.

PMID- 14577520
TI  - Serum metalloproteinase 9 levels in patients with coronary artery disease: a
      novel marker of inflammation.
AB  - BACKGROUND: The finding that expression of metalloproteinases (MMPs) is induced
      in atherosclerotic plaques prone to rupture suggests the possibility that
      patients with atherosclerotic diseases would show enhanced blood levels of MMPs
      and that MMPs might represent a potential inflammatory risk factor for
      atherosclerosis. Therefore, the present study was aimed at verifying whether MMPs
      may represent sensitive markers of inflammation in patients with coronary artery
      disease. METHODS: MMP-2, MMP-9, interleukin (IL)-6, C-reactive protein (CRP), and
      fibrinogen levels were measured in blood samples obtained from 66 cases with
      previous acute myocardial infarction and 66 control subjects similar for age,
      sex, and major atherosclerotic risk factors but without history or evidence of
      atherothrombotic diseases. RESULTS: Biohumoral markers of inflammation and MMP-9
      levels were significantly elevated in cases compared with controls (median values
      40.6 versus 9.8 ng/mL; p < .0001), whereas MMP-2 levels did not differ between
      the two groups (median values 839 versus 873 ng/mL; p = .53). A direct
      correlation was found among MMP-9, CRP, IL-6, and fibrinogen levels. Conditional
      logistic regression analysis showed that MMP-9 is related to myocardial
      infarction (p = .006) even after adjusting for cardiovascular medications and
      CRP. CONCLUSION: These findings suggest that measurement of serum MMP-9 levels
      may represent a novel marker of inflammation in patients with known coronary
      artery disease and might provide an index of plaque activity in this clinical
      setting.

PMID- 14577521
TI  - The current impossibility of peer review.

PMID- 14577522
TI  - Radiologic case study. Soft-tissue chondroma.

PMID- 14577523
TI  - Intramedullary fixation of humeral shaft fractures using an inflatable nail.

PMID- 14577524
TI  - Computer-assisted total knee arthroplasty: navigation in TKA.

PMID- 14577525
TI  - A cost analysis of bone morphogenetic protein versus autogenous iliac crest bone
      graft in single-level anterior lumbar fusion.
AB  - An economic model was developed to compare costs of stand-alone anterior lumbar
      interbody fusion with recombinant human bone morphogenetic protein 2 on an
      absorbable collagen sponge versus autogenous iliac crest bone graft in a tapered
      cylindrical cage or a threaded cortical bone dowel. The economic model was
      developed from clinical trial data, peer-reviewed literature, and clinical expert
      opinion. The upfront price of bone morphogenetic protein (3380 dollars) is likely
      to be offset to a significant extent by reductions in the use of other medical
      resources, particularly if costs incurred during the 2 year period following the
      index hospitalization are taken into account.

PMID- 14577526
TI  - Complications and surgical considerations in posterior lumbar interbody fusion
      with carbon fiber interbody cages and Steffee pedicle screws and plates.
AB  - Sixty consecutive patients undergoing posterior lumbar interbody fusion with a
      carbon fiber cage and posterolateral fusion using Steffee VSP (Depuy, Raynham,
      Mass) pedicle screw and plate instrumentation were reviewed. Perioperative
      complications, operative blood loss, and operative time were evaluated. Six dural
      tears, three transient sensory deficits, and two cases of deep venous thrombosis
      were reported. Operative blood loss for primary cases averaged 269 cc for one
      level and 569 cc for two levels fused. Patients with prior surgery averaged 378
      cc for one level and 470 cc for two levels fused. Operative time for primary
      cases averaged 202 minutes for one level and 251 minutes for two levels fused.
      Patients with prior surgery required 208 minutes for one level and 251 minutes
      for two levels fused. Posterior lumbar interbody fusion with instrumented
      posterolateral fusion can be performed with a low intraoperative complication
      rate. Blood loss and operative time compare favorably with alternative methods of
      obtaining 360 degree fusion. Radiographic fusion was obtained in 100% of
      patients. Outcome analysis revealed 67% excellent or good results.

PMID- 14577527
TI  - Relationship between mortality and proximal femur fractures in the elderly.
AB  - Four hundred ninety-three patients aged > 65 years with proximal femur fractures
      were examined to assess the mortality rate within 1 year postoperatively. The
      risk factors that are most often associated with death were identified. Within
      the inhomogeneous group of patients, mortality was significantly higher in
      patients with poor mental status, with > or = 2 pre-existing diseases, a 3 or 4
      American Society of Anesthetists class rating, and a lateral fracture. Regarding
      treatment and rehabilitation, special attention needs to be paid to these
      patients postoperatively.

PMID- 14577528
TI  - Minimally invasive surgical techniques for the reconstruction of calcaneal
      fractures.
AB  - The soft tissues play a crucial part in both the stabilization of the multiple
      joint surfaces of the calcaneus and in allowing propulsion as needed. Therefore,
      minimally invasive functional stabilization of heel bone fracture is a promising
      technique, which may bypass all published controversies. Experience has shown
      that ligamentotaxis, which means the use of mechanical forces applied to the soft
      tissue envelope of fractures without the surgical disruption of the latter,
      contributes to fracture healing and reconstruction. Therefore, based on our
      results, minimally invasive techniques are useful and promising in calcaneal
      fracture treatment.

PMID- 14577529
TI  - Successful antibiotic treatment for a cervical spinal cord abscess following a
      stab injury on the neck.

PMID- 14577530
TI  - Peroneus longus rupture following a modified Evans lateral ankle ligament
      reconstruction.

PMID- 14577531
TI  - Odontoid fracture in a 50-year-old patient presenting 40 years after cervical
      spine trauma.

PMID- 14577533
TI  - Scene-based Shack-Hartmann wave-front sensing: analysis and simulation.
AB  - In many situations it is not possible for an adaptive optics system to use a
      point source to measure the phase derivative, such as imaging along slant paths
      through the atmosphere and observation of the earth from space with a lightweight
      optic. Instead, small subimages of the observed scene can be used in a scene
      based wave-front sensing technique. This study presents three important advances
      in the understanding of this technique. Rigorous analysis shows how slope
      estimation performance depends precisely on scene content and illumination.
      Scaling laws for changes in illumination are derived. The technique, when applied
      to point sources, is more robust to detect size changes and background levels
      than current methods.

PMID- 14577532
TI  - Osteoarthritis and beyond: a consensus on the past, present, and future of
      hyaluronans in orthopedics.

PMID- 14577534
TI  - Imaging phase objects with square-root, Foucault, and Hoffman real filters: a
      comparison.
AB  - Methods of imaging phase objects are considered. First the square-root filter is
      inferred from a definition of fractional-order derivatives given in terms of the
      integration of a fractional order called the Riemann-Liouville integral. Then we
      present a comparison of the performance of three frequency-domain real filters:
      square root, Foucault, and Hoffman. The phase-object imaging method is useful as
      a phase-shift measurement technique under the condition that the output image
      intensity is a known function of object phase. For the square-root filter it is
      the first derivative of the object phase function. The Foucault filter, in spite
      of its position, gives output image intensities expressed by Hilbert transforms.
      The output image intensity obtained with the Hoffman filter is not expressed by
      an analytical formula. The performance of the filters in a 4f imaging system with
      coherent illumination is simulated by use of VirtualLab 1.0 software.

PMID- 14577535
TI  - Holodiagrams in birefringent media.
AB  - The modifications to the holodiagram concept to describe free propagation (the
      extraordinary ray) inside birefringent materials are described. Holodiagrams are
      graphs showing the loci where the sum or the difference in the optical path from
      a generic point to two foci is the same. The holodiagrams obtained in this way
      give the shape of the surfaces that satisfy Fermat's principle, conjugate by
      reflection of one focus into the other, and represent the interference fringes
      obtained if both points are coherent sources. The reflection law in birefringent
      media is investigated in relation to this diagram. One direction for the optical
      axis is considered: parallel to the line joining the source and the observation
      point. Quartz-type and calcite-type crystals are studied.

PMID- 14577536
TI  - Reconstructing two-dimensional acoustic object fields by use of digital phase
      conjugation of scanning laser vibrometry recordings.
AB  - A scanning laser Doppler vibrometer is used to record two-dimensional ultrasound
      fields in air. The laser light of the vibrometer traverses the sound field to and
      from a rigid reflector and determines the velocity field, a quantity proportional
      to the sound pressure rate, in each scanned point relative to the sound source.
      The object sound is the scattered field from objects outside the recording area.
      Digital reconstruction by use of phase conjugation (time reversal) of the object
      sound field is then performed, and the original object field intensity and phase
      is reconstructed.

PMID- 14577537
TI  - Diffusion-based model to predict the conservation of gratings recorded in
      poly(vinyl alcohol)-acrylamide photopolymer.
AB  - Photopolymers are interesting materials for use in recording information in
      holography. We study the holographic behavior and stability of volume holograms
      recorded in poly(vinyl alcohol)--acrylamide photopolymers with and without a
      cross linker. Using a first-harmonic diffusion model, we analyze the residual
      monomer that remains when volume diffraction gratings are recorded in
      photopolymer materials. The importance of this residual monomer to the stability
      of the gratings is evaluated.

PMID- 14577538
TI  - Temporal phase unwrapping of digital hologram sequences.
AB  - A method for recording and evaluating digital image-plane holograms is presented.
      Hundreds of holograms of an object that has been subjected to dynamic deformation
      (e.g., vibrations) are recorded. The phase of the wave front is calculated from
      the recorded holograms by use of a two-dimensional digital Fourier-transform
      method. By temporal phase unwrapping it is possible to determine the absolute
      deformation (included the direction of motion) of the object. Experimental
      results are presented, and the advantages of temporal phase unwrapping compared
      with spatial phase unwrapping are discussed.

PMID- 14577539
TI  - Content-based searching of multimedia databases by use of approximate digital
      signatures.
AB  - We propose the use of approximate digital signatures of selected multimedia
      feature vectors for fast content-based retrieval in large multimedia databases.
      We adapt and extend the approximate message authentication code (AMAC),
      introduced by some of the authors recently in the area of message authentication,
      to the multimedia searching problem. An AMAC is a binary signature with the
      ability to reflect changes in the message it represents. The Hamming distance
      between two AMACs is used to measure the degree of the similarity between
      multimedia objects. We develop a method to compress AMAC signatures to create a
      direct look-up table that allows for fast searching of a database. The color
      histogram is used as the example feature space to show how the signature is
      applied. Experimental results show that the performance of the proposed method is
      comparable with existing methods based on other popular metrics, but it
      significantly decreases search time.

PMID- 14577540
TI  - Scene-based nonuniformity correction for focal plane arrays by the method of the
      inverse covariance form.
AB  - What is to our knowledge a new scene-based algorithm for nonuniformity correction
      in infrared focal-plane array sensors has been developed. The technique is based
      on the inverse covariance form of the Kalman filter (KF), which has been reported
      previously and used in estimating the gain and bias of each detector in the array
      from scene data. The gain and the bias of each detector in the focal-plane array
      are assumed constant within a given sequence of frames, corresponding to a
      certain time and operational conditions, but they are allowed to randomly drift
      from one sequence to another following a discrete-time Gauss-Markov process. The
      inverse covariance form filter estimates the gain and the bias of each detector
      in the focal-plane array and optimally updates them as they drift in time. The
      estimation is performed with considerably higher computational efficiency than
      the equivalent KF. The ability of the algorithm in compensating for fixed-pattern
      noise in infrared imagery and in reducing the computational complexity is
      demonstrated by use of both simulated and real data.

PMID- 14577541
TI  - Pose estimation from a two-dimensional view by use of composite correlation
      filters and neural networks.
AB  - We present a technique to estimate the pose of a three-dimensional object from a
      two-dimensional view. We first compute the correlation between the unknown image
      and several synthetic-discriminant-function filters constructed with known views
      of the object. We consider both linear and nonlinear correlations. The filters
      are constructed in such a way that the obtained correlation values depend on the
      pose parameters. We show that this dependence is not perfectly linear, in
      particular for nonlinear correlation. Therefore we use a two-layer neural network
      to retrieve the pose parameters from the correlation values. We demonstrate the
      technique by simultaneously estimating the in-plane and out-of-plane orientations
      of an airplane within an 8-deg portion. We show that a nonlinear correlation is
      necessary to identify the object and also to estimate its pose. On the other
      hand, linear correlation is more accurate and more robust. A combination of
      linear and nonlinear correlations gives the best results.

PMID- 14577542
TI  - Radar-echo tracking by use of invariant moments.
AB  - A number of techniques to track rainfall patterns by use of radar observations
      have been developed over the years. We present a method for radar-echo tracking
      based on Hu invariant moments. The method has been tried on several sequences of
      test images, and the derived displacement fields were in good agreement with the
      real motions of the tested objects. For the real data obtained from the
      conventional meteorological radar in Legionowo the method occasionally failed
      when changes in the radar echo between observations were too large.

PMID- 14577543
TI  - Comparison of linear and rotationally shearing interferometric layouts for
      extrasolar planet detection from space.
AB  - We use the point spread function and the modulation transfer function (MTF) as
      two figures-of-merit to evaluate the performance of the multiaperture
      interferometric configurations for the detection of a faint planet in the
      vicinity of its bright star. We design nonredundant interferometric layouts that
      provide satisfactory coverage of the spatial frequencies of interest. We propose
      a design incorporating a rotating, rotationally shearing interferometer in a
      gravity-free environment and compare its performance with the Earth-based, fixed,
      linear configurations. The side peak of its MTF may be centered on the coordinate
      associated with a likely planet spatial frequency, resulting in planet signal
      enhancement and isolation.

PMID- 14577544
TI  - Determination of the optimum cluster parameters in a clustered free-space optical
      interconnect.
AB  - A model for a clustered free-space optical interconnect is developed and is used
      to determine the maximum array density that can be achieved, together with the
      optimal cluster parameters that maximize this density. This model includes
      misalignment tolerance and the impact of multimode vertical-cavity surface
      emitting laser beams. We find that for short interconnect distances, the maximum
      channel density is limited by the speed of the relay lenses, but as the
      interconnect distance increases, geometric aberrations become the limiting
      factor. We also determine the interconnect distance below which a micro-channel
      relay is more suitable and the distance above which a single-lens solution is
      adequate.

PMID- 14577545
TI  - Photoinduced anisotropy in a family of amorphous azobenzene polyesters for
      optical storage.
AB  - We investigate parameters associated with optical data storage in a variety of
      amorphous side-chain azobenzene-containing polyesters denoted as E1aX. The
      polyesters possess a common cyano-substituted azobenzene chromophore as a side
      chain, but differ in their main-chain polyester composition. Seventeen different
      polymers from the E1aX family divided into four classes, depending on the type of
      the main-chain substituent (one-, two-, and three-ring aromatic or alicyclic)
      have been thoroughly investigated. Various parameters characterizing the
      photoinduced birefringence in these materials, such as the response time, thermal
      and light stability, and long-term stability under ambient light at room
      temperature have been measured. Each of these parameters is quantitatively
      represented and therefore it is possible to make a clear comparison between the
      properties of the polymers. The results indicate that the long-term stability at
      ambient temperature is closely related to the thermal stability of the
      photoinduced birefringence. A strong correlation has also been found between the
      response time and the stability of the induced anisotropy toward illumination
      with unpolarized white light. One of the classes of E1aX polymers characterized
      by two-ring aromatic substituent in the main chain is a good candidate for
      optical data storage media. A recording energy of approximately 2 J/cm2 is
      sufficient to induce high refractive-index modulations of deltan = 0.13 in these
      materials, which is retained even at elevated temperatures (>130 degrees C). Long
      term stability of greater than one year for the induced anisotropy has also been
      achieved.

PMID- 14577546
TI  - Elemental versus configural perception in a people-present/people-absent
      discrimination task by pigeons.
AB  - In the present experiment, we investigated whether pigeons rely exclusively on
      elemental information or whether they are also able to exploit configural
      information in a people-present/people-absent discrimination task. Six pigeons
      were trained in a go/no-go procedure to discriminate between 800 color
      photographs characterized by the presence or absence of people. The people
      present stimuli were designated as positive, and the people-absent stimuli were
      designated as negative. After training and a subsequent generalization test, the
      pigeons were presented with both familiar and novel people-present stimuli
      containing human figures that were distorted in one of seven different ways. All
      the pigeons learned the initial discrimination and also showed generalization to
      novel stimuli. In the subsequent test, performance on all types of distorted
      stimuli was diminished in comparison with that on the intact original pictures
      from which they had been derived. At the same time, however, peck rates clearly
      exceeded the level of responding found for regular people-absent stimuli. This
      result strongly suggests that responding was controlled by both the constituting
      target components and their spatial relations and, therefore, points to the dual
      importance of elemental and configural information.

PMID- 14577548
TI  - Temporal integration and temporal backward associations in human and nonhuman
      subjects.
AB  - Two experiments are reported that demonstrate temporal integration of
      independently acquired temporal relationships, including backward associations,
      in both human (Experiment 1) and nonhuman (rats, Experiment 2) subjects. The
      experiments were designed and analyzed in the framework of the temporal coding
      hypothesis (e.g., Matzel, Held, & Miller, 1988; Savastano & Miller, 1998) as a
      strategy toward illuminating the use of temporal information and assessing the
      existence of temporal backward associations. Both experiments provided evidence
      of retrieval of associations to an event that was expected to occur prior to the
      moment in time at which a stimulus was presented (i.e., backward associations).
      In addition, Experiment 1 constitutes the first controlled demonstration of
      temporal integration by human subjects.

PMID- 14577547
TI  - The effect of rate of reinforcement and time in session on preference for
      variability.
AB  - Pigeons pecked keys on concurrent-chains schedules that provided a variable
      interval 30-sec schedule in the initial link. One terminal link provided
      reinforcers in a fixed manner; the other provided reinforcers in a variable
      manner with the same arithmetic mean as the fixed alternative. In Experiment 1,
      the terminal links provided fixed and variable interval schedules. In Experiment
      2, the terminal links provided reinforcers after a fixed or a variable delay
      following the response that produced them. In Experiment 3, the terminal links
      provided reinforcers that were fixed or variable in size. Rate of reinforcement
      was varied by changing the scheduled interreinforcer interval in the terminal
      link from 5 to 225 sec. The subjects usually preferred the variable option in
      Experiments 1 and 2 but differed in preference in Experiment 3. The preference
      for variability was usually stronger for lower (longer terminal links) than for
      higher (shorter terminal links) rates of reinforcement. Preference did not change
      systematically with time in the session. Some aspects of these results are
      inconsistent with explanations for the preference for variability in terms of
      scaling factors, scalar expectancy theory, risk-sensitive models of optimal
      foraging theory, and habituation to the reinforcer. Initial-link response rates
      also changed within sessions when the schedules provided high, but not low, rates
      of reinforcement. Within-session changes in responding were similar for the two
      initial links. These similarities imply that habituation to the reinforcer is
      represented differently in theories of choice than are other variables related to
      reinforcement.

PMID- 14577549
TI  - Timing in retroactive interference.
AB  - Retroactive interference is conventionally viewed as attenuated retrieval of a
      target association due to the training of a second association between training
      and testing of the target association. In three experiments in which water
      deprived rats were used as subjects, we manipulated the durations of the time
      between cue termination and outcome onset (Experiment 1), the durations of the
      target and the interfering cues (Experiment 2), and the durations of the outcome
      used during target and interfering training (Experiment 3). Greater interference
      was consistently observed between associations bearing a high degree of
      similarity in their temporal structure, which suggests that interference occurs
      between complex representations that encode not only the physical attributes of
      the stimuli, but also their temporal characteristics.

PMID- 14577550
TI  - Competition between ethanol-induced reward and aversion in place conditioning.
AB  - Previous place conditioning studies in mice have shown that injection of ethanol
      immediately before a conditioned stimulus (CS+) produces conditioned preference,
      whereas injection of ethanol immediately after CS+ produces conditioned aversion.
      In the present experiments, we examined the learning that occurs when ethanol is
      injected in "ambiguous" procedures that provide the opportunity for both types of
      conditioning. When ethanol was given midway through the CS (Experiments 1 and 2)
      or both before and after the CS (Experiment 3), the direction of place
      conditioning was the same as when mice were exposed only to whichever contingency
      occurred first (a primacy effect). That is, injection of ethanol in the middle of
      the CS conditioned aversion, whereas injection both before and after the CS
      conditioned preference. Because these results support the idea that ethanol
      elicits both aversive and rewarding effects, they are most consistent with
      conditioning theories that conceptualize unconditioned stimuli (USs) as events
      that can activate multiple representational components.

PMID- 14577551
TI  - Negative priming and occasion setting in an appetitive Pavlovian procedure.
AB  - Rats received training in which two auditory target stimuli, X and Y, were
      signaled by two visual stimuli, A and B, and followed by food (i.e., A-->X+, B-
      >Y+). The test consisted of presentations of X and Y preceded either by the same
      signal as during training (same trials: A-->X, B-->Y) or by the alternative
      signal (different trials: A-->Y, B-->X). After 8 training sessions, the animals
      responded less on same trials than on different trials; this effect was
      significantly reduced after 24 training sessions. In two additional experiments,
      animals that had also experienced presentations of A and B alone, either before
      or during training, showed the opposite pattern of results, responding more on
      same trials than on different trials. These results are interpreted as being due
      to the interaction between the effects of occasion setting and negative priming
      (see Wagner, 1981).

PMID- 14577552
TI  - Conditioning-specific reflex modification of the rabbit (Oryctolagus cuniculus)
      nictitating membrane response: US intensity effects.
AB  - Conditioning-specific reflex modification (CRM) of the rabbit's nictitating
      membrane response (NMR) describes changes in responding to an unconditioned
      stimulus (US) when the rabbit is tested in the absence of the conditioned
      stimulus. Specifically, after at least 3 days of tone-electrical stimulation
      pairings, responses to the US increase in size, especially at intensities weaker
      than the training intensity. CRM is similar to classical conditioning in that it
      is a function of the strength of conditioning, it can be extinguished, and it can
      be generalized from one stimulus to another. To compare CRM and classical
      conditioning further, we conducted three experiments to examine the effects of US
      intensity (1.0, 2.0, and 4.0 mA) on CRM. CRM was weak following conditioning with
      1.0 mA and extremely strong following conditioning with 2.0 mA and 4.0 mA. The
      data suggest that CRM is a function of US intensity and have implications for
      posttraumatic stress disorder, a disorder potentially modeled by CRM.

PMID- 14577553
TI  - Recovery effects after extinction in the Morris swimming pool navigation task.
AB  - In three experiments in which rats were used as subjects, we developed an
      extinction procedure using a Morris pool. The animals were trained to find a
      hidden platform located at a fixed position and were then given extinction trials
      in which the platform was removed from the pool. When training and extinction
      were carried out in the same context and time was allowed to elapse between
      extinction and test, spontaneous recovery of learning was observed. On the other
      hand, those rats that received extinction in a context different from the one
      used for training failed to show spontaneous recovery of learning when tested in
      the extinction context after an interval of 96 h. However, they did show renewal
      of spatial learning when tested in the training context. These results show that
      extinction in the spatial domain behaves like extinction in standard conditioning
      preparations.

PMID- 14577554
TI  - Our founders would be proud.

PMID- 14577555
TI  - Medical memory bank.

PMID- 14577556
TI  - The history of the MMA.

PMID- 14577557
TI  - Called up.

PMID- 14577558
TI  - University base hospitals.

PMID- 14577559
TI  - Lundy's legacy.

PMID- 14577560
TI  - Open-heart pioneers.

PMID- 14577561
TI  - Tobacco and the times.

PMID- 14577562
TI  - Doctors to the town.

PMID- 14577563
TI  - Aviation medicine at Mayo.

PMID- 14577564
TI  - Setting up solo.

PMID- 14577565
TI  - One doctor's records.

PMID- 14577567
TI  - A fraternity for women.

PMID- 14577566
TI  - The Eitels and their hospital.

PMID- 14577568
TI  - Pioneer in student health services.

PMID- 14577569
TI  - "The first adequate graduate school of medicine in America": a brief history of
      the University of Minnesota-Mayo Graduate School of Medicine.

PMID- 14577570
TI  - Reactive oxygen species play roles on B cell surface receptor CD40-mediated
      proximal and distal signaling events: effects of an antioxidant, N-acetyl-L
      cysteine treatment.
AB  - Reactive oxygen species (ROS) have been indicated as important signal mediators
      for many cell surface receptors. We previously demonstrated that ROS are
      generated by cross-linking surface receptor CD40 and consequently induce c-Jun N
      terminal kinase activation and interleukin-6 secretion in murine B cells. In this
      study, we investigated further the involvement of ROS in CD40-mediated signaling
      events in B cells. CD40-mediated proximal events, which include protein serine
      phosphorylation, protein translocation between membranes and cytosol, as well as
      receptor complex formation, were inhibited after the pre-incubation of cells with
      an antioxidant N-acetyl-L-cysteine (NAC). Additionally, B cell responses after
      long-term ligation of CD40, such as protein expression, nuclear transcription
      factor kappaB (NFkappaB) activation, and cell proliferation, were also affected
      when cells were treated with NAC. These data suggest that CD40-induced ROS play
      critical roles in CD40-mediated B cell regulation.

PMID- 14577571
TI  - Regulation of the expression and activity of beta1,4-galactosyltransferase I by
      focal adhesion kinase.
AB  - beta1,4-Galactosyltransferase I (GalT) participates in both glycoconjugates and
      cellular interactions. GalT's role in lamellipodia formation and cell migration
      on laminin is associated with a transient phosphorylation of focal adhesion
      kinase (FAK) and a consequent reorganization of the actin cytoskeleton and focal
      adhesions. We transfected wild type FAK and different FAK mutants into NIH3T3
      cell line, measured GalT gene expression by Northern blot hybridization, and
      evaluated its activity. It was found that wtFAK and FAKY576F up-regulated GalT
      gene expression and its surface activity, while FAKY397F down-regulated them. At
      the same time, we used ricinus communis agglutinin (RCA)-I lectin staining to
      demonstrate its binding reactions. We found that wtFAK and FAKY576F bound
      stronger, while FAKY397F bound weaker than the control. By flow cytometry
      analysis, it was found that FAK promoted G1/S transition and enhanced the
      expression of cyclin D1 while FAKY397F inhibited these steps compared with the
      control NIH3T3 cells. G1/S checkpoint regulation proteins control GalT mRNA
      transcription. The results indicate that FAK regulated the expression of GalT and
      its activity in NIH3T3 cells may contribute to the effect of FAK on the cell
      cycle.

PMID- 14577572
TI  - Cytoprotection against ischemia-induced DNA cleavages and cell injuries in the
      rat liver by pro-vitamin C via hydrolytic conversion into ascorbate.
AB  - To search a regimen for prevention of post-ischemic reperfusional (I/R) injuries,
      I/R in the liver was induced by 30-min clamping and subsequent unfastening of the
      portal vein of a rat, which underwent previous i.v. administration with ascorbic
      acid (Asc) of 1 mg/kg or the autooxidation-resistant pro-vitamin C, 2-O-alpha-D
      glucosylated Asc (Asc2G) or 2-O-phosphorylated Asc (Asc2P) of 1 mg Asc
      equivalent/kg from the viewpoint of utilization of antioxidants that can promptly
      scavenge I/R-derived reactive oxygen species. The administration with Asc, Asc2P
      or Asc2G prevented some features of hepatic I/R injuries such as release of
      hepatic marker enzymes GOT and GPT into the blood vessel, cellular degenerative
      symptoms including vacuolation and cell fragmentation, and nuclear DNA strand
      cleavage as detected by TUNEL staining. The preventive effects on I/R injuries
      were in the order: Asc2G > Asc2P >> Asc. This order of preventive degrees of
      three anti-oxidants is partly attributable to proper efficiency of conversion to
      vitamin C and stability in blood stream; Asc2P was moderately converted to a free
      monoanion form of Asc in human serum, but, in rat serum, so efficiently converted
      to Asc as to undergo the resultant oxidative decomposition before reaching the
      liver, whereas Asc2G underwent scarce conversion to Asc in human serum but
      moderate conversion in rat serum, suggesting that Asc2P might be less
      cytoprotective against I/R injury than Asc2G in the rat liver in a way different
      from the human liver. In contrast Asc was so susceptible to autooxidation as to
      be rapidly decomposed in either rat or human serum. The concentrations of
      ascorbyl radicals (AscR) in serum were unchanged during I/R for sham-operated
      rats, but appreciably diminished time-dependently for I/R-operated rats as shown
      by ESR spectra. A marked increase in serum AscR occurred in rats receiving Asc,
      Asc2G or Asc2P, but it was time-dependently restored down to the pre-ischemic
      level of AscR in I/R-operated rats more rapidly than in sham-operated rats. Thus,
      hepatic I/R injuries were shown to be prevented more markedly by Asc2G or Asc2P
      than by Asc, which is attributable to efficiencies of both vitamin C conversion
      and subsequent AscR retention.

PMID- 14577573
TI  - Cardiac expression of urocortin (Ucn) in diseased heart; preliminary results on
      possible involvement of Ucn in pathophysiology of cardiac diseases.
AB  - Recently, several studies reported that urocortin (Ucn) had beneficial effects on
      cardiovascular system and was expressed both in the normal heart and in the heart
      of dilated cardiomyopathy (DCM), yet the relationship between high expression of
      Ucn and pathophysiology of Ucn in diseased heart has been discussed. Thus, the
      present study was designed to elucidate the expression of Ucn in the diseased
      heart by immunohistochemical approach using endomyocardial biopsy specimens. The
      involvement of immunoreactive Ucn in pathophysiology of cardiac disease was
      evaluated using endomyocardial biopsy specimens obtained from the patients with
      some heart diseases, including DCM and hypertrophic cardiomyopathy (HCM). Ucn was
      detected in all endomyocardial biopsy specimens of ventricular tissue obtained
      from the patients with such cardiac diseases, a specimens of atrial tissue, and
      normal heart specimens obtained from autopsy cases. In DCM patients, left
      ventricular end-diastolic pressure significantly elevated in severely stained
      group. On the contrary, in HCM patients, left ventricular ejection fraction was
      higher in the severely stained group. Ucn was expressed more abundantly in the
      diseased heart, especially in HCM and DCM, than in the normal heart. In
      conclusion, such close relationship between Ucn expression in the heart and
      cardiac function indicated that clinical features of Ucn resembled those of
      norepinephrine and Ucn could play a certain pathophysiological roles in the
      cardiac diseases.

PMID- 14577574
TI  - Transcriptional control of the DNA methyltransferases is altered in aging and
      neoplastically-transformed human fibroblasts.
AB  - Although it has been known for quite some time that genomic methylation is
      significantly altered in aging and neoplastic tissues and cells, the underlying
      mechanisms responsible for these alterations are not yet known. Since DNA
      methylation affects many different cellular processes including, most
      significantly, gene expression, elucidation of the basis for aberrations in DNA
      methylation in aging and cancer is of high priority. To address this problem, we
      sought to analyze changes in gene expression, protein production and enzyme
      activity of the three major DNA methyltransferases (Dnmtl, 3a, and 3b) in aging
      and neoplastically-transformed WI-38 human fetal lung fibroblasts. We have found
      that the gene expression of each of the three Dnmts parallels changes in protein
      production and enzyme activity of the Dnmts not only in aging cells, but also in
      WI-38 fibroblasts induced to undergo neoplastic transformation using defined
      genetic elements. These findings strongly implicate change in gene expression as
      an underlying mechanism in the altered genomic methylation of these cells.
      Striking changes in the gene expression of the Dnmts were observed in aging cells
      with the mRNA of Dnmtl becoming reduced while the mRNA of Dnmt3b increased
      steadily in aging cells consistent with our observations in protein production
      and activity of these enzymes. Surprisingly, Dnmt3a actually decreased in gene
      expression in aging cells. We therefore propose that the transcriptional control
      of Dnmt1, the predominant maintenance methyltransferase, is significantly
      suppressed in aging cells and contributes to the reduced genomic methylation of
      these cells. The paradoxical sporadic gene hypermethylation in aging cells
      appears to be related to transcriptional up-regulation of the Dnmt3b gene. In
      addition, we sought to explore the coordinated changes in gene expression,
      protein production, and enzyme activity of these Dnmts in early cellular
      transformation. In these cells, the gene expression of all the three major Dnmts
      were up-regulated followed by marked increases in Dnmt protein and enzyme
      activity. These results therefore collectively indicate that changes in
      transcriptional control of the Dnmts are the likely cause for the known
      alterations in DNA methylation in aging cells and in cells undergoing
      tumorigenesis. They also show that changes in transcription of Dnmtl and Dnmt3b
      are probably most important in affecting the generalized hypomethylation and
      specific hypermethylation seen in aging cells while gene expression of all the
      Dnmts is significantly increased in cancer cells. These findings should have
      broad implications in elucidating the underlying causes of changes in DNA
      methylation in aging and tumorigenesis and point to variations in gene expression
      of the individual Dnmts as a likely mechanism involved in these processes.

PMID- 14577575
TI  - Protein glycans alteration and a different distribution of some enzymatic
      activities involved in the glycan processing are found in AZT-treated K562 cells.
AB  - In this paper we report that 3'-azido-3'-deoxythymidine (AZT) treatment of human
      erythroleukemia (K562) cells greatly alters the pattern of protein glycans and
      significantly modifies beta,(1 --> 4)galactosyltransferase, beta-galactosidase,
      and alpha,(2 --> 8)sialyltransferase activities. In particular, AZT-treated K562
      cells exhibited a decreased incorporation of sialic acid (86% of control) into
      protein glycans, being the reduced alpha,(2 --> 6) incorporation almost of the
      same magnitude with respect to that of alpha,(2 --> 3) (93 and 90% of control,
      respectively). Moreover, the drug exposure of cells induced a decrease of both
      mannose terminally linked and galactose linked as beta,(1 --> 4) (90 and 92% of
      control, respectively) and a significant increase of galactose beta,(1 --> 3)
      (112% of control). In addition, beta,(1 --> 4)galactosyltransferase and beta
      galactosidase activities were found enhanced in K562-treated cells (30 and 12%,
      respectively), while alpha,(2-8 )sialyltransferase activity decreased (75% of
      control). Sialyltransferase activities of other types i.e. 30, 60, 3 N, 6 N, did
      not show any appreciable differences irrespective of AZT-treatment. Besides
      previous studies which report that AZT exposure of K562 cells, indirectly
      prevents nucleotide-sugar import into the Golgi complex, with consequent
      inhibition of glycosylation, our observations show for the first time that AZT
      affects several enzymatic activities involved in specific glycosylation reactions
      leading, in turn, to protein glycans alteration.

PMID- 14577576
TI  - Postanoxic functional recovery of the developing heart is slightly altered by
      endogenous or exogenous nitric oxide.
AB  - Nitric oxide synthase (NOS) is strongly and transiently expressed in the
      developing heart but its function is not well documented. This work examined the
      role, either protective or detrimental, that endogenous and exogenous NO could
      play in the functioning of the embryonic heart submitted to hypoxia and
      reoxygenation. Spontaneously beating hearts isolated from 4-day-old chick embryos
      were either homogenized to determine basal inducible NOS (iNOS) expression and
      activity or submitted to 30 min anoxia followed by 100 min reoxygenation. The
      chrono-, dromo- and inotropic responses to anoxia/reoxygenation were determined
      in the presence of NOS substrate (L-arginine 10 mM), NOS inhibitor L-NIO (1-5
      mM), or NO donor (DETA NONOate 10-100 microM). Myocardial iNOS was detectable by
      immunoblotting and its activity was specifically decreased by 53% in the presence
      of 5 mM L-NIO. L-Arginine, L-NIO and DETA NONOate at 10 microM had no significant
      effect on the investigated functional parameters during anoxia/reoxygenation.
      However, irrespective of anoxia/reoxygenation, DETA NONOate at 100 microM
      decreased ventricular shortening velocity by about 70%, and reduced atrio
      ventricular propagation by 23%. None of the used drugs affected atrial activity
      and hearts of all experimental groups fully recovered at the end of
      reoxygenation. These findings indicate that (1) by contrast with adult heart,
      endogenously released NO plays a minor role in the early response of the
      embryonic heart to reoxygenation, (2) exogenous NO has to be provided at high
      concentration to delay postanoxic functional recovery, and (3) sinoatrial
      pacemaker cells are the less responsive to NO.

PMID- 14577577
TI  - Nitric oxide and iron metabolism in exercised rat with L-arginine
      supplementation.
AB  - The present study was designed to investigate whether L-arginine (Arg)
      supplementation in exercise affects nitric oxide (NO) synthesis in tissues and
      thus iron metabolism. Rats were assigned to one of four groups: EG (Exercise), SG
      (Sedentary), EAG (Exercise + Arg), and SAG (Sedentary + Arg). Both EG and EAG
      swam 2 h/day for 3 months. Both SAG and EAG received 3% Arg supplementation in
      their drinking water. The results showed that Arg supplementation in exercise
      (EAG) significantly increased nitrite and nitrate (NOx) concentration in the
      kidney and BMC, rather than in the liver, spleen and heart. Arg supplementation
      significantly increased both nonheme iron (NHI) and catalytic iron (CI) content
      in the kidney, to the extent that the ratio of CI/NHI or storage iron (SI)/NHI
      was not significantly affected, and significantly decreased NHI content and
      increased CI content in BMC, to the extent that SI content or SI/NHI was
      significantly decreased. These findings suggest that Arg supplementation in
      exercise, possibly through increasing NO synthesis, may change CI formation in
      the kidney and BMC, and affect iron storage in BMC rather than in the kidney.

PMID- 14577578
TI  - Identification of a new missense mutation in the mtDNA of hereditary
      hypertrophic, but not dilated cardiomyopathic hamsters.
AB  - The cardiomyopathic hamster is characterized by a naturally occurring deletion in
      the delta-sarcoglycan gene generating either the hypertrophic or the dilatative
      phenotype of cardiomyopathy. This evidence suggests that other genetic or
      environmental factors might concur to the pathogenesis of cardiomyopathy. The aim
      of the present study was to investigate on the possibility that other genes are
      involved in the pathogenesis of hamster cardiomyopathy. For this purpose, a
      series of genes of cardiomyopathic and healthy hamsters were compared by the
      differential display technique. The hamster cytochrome c oxidase mitochondrial
      subunit III (COIII) gene has been sequenced and identified as the gene
      upregulated in brain and skeletal muscle. The gene sequencing and restriction
      analysis demonstrated that a missense mutation is present in the COIII gene of
      hamsters exhibiting hypertrophic cardiomyopathy while no mutations were present
      in dilatative cardiomyopathic hamsters. The mutation was heteroplasmic and the
      heteroplasmy level was increased with age in skeletal muscle and heart. The
      ultrastructural analysis of cardiac tissue showed severe damage in the
      mitochondrial structure of hypertrophic but not dilatative hamster hearts. These
      results suggest that the pathogenesis of the cardiac damage in hypertrophic
      cardiomyopathic hamster may be sustained by multiple mutations exerting a
      cumulative effect on both structure and function of cardiac muscle.

PMID- 14577579
TI  - PD-136,450: a CCK2 (gastrin) receptor antagonist with antisecretory, anxiolytic
      and antiulcer activity.
AB  - This study investigated the effects of PD-136,450 (PD), a highly selective ligand
      for the CCK2 receptor, on gastric acid and pancreatic secretions, gastric
      cytoprotection and anxious behaviour in the rat and rabbit. PD inhibited gastrin
      (but not dimaprit) stimulated acid secretion in anaesthetized and conscious rats
      (IC50 of 1 mg kg(-1) sc) and inhibited 14C-aminopyrine uptake in isolated gastric
      glands from rabbits. In addition, PD decreased dose-dependently gastric
      haemorrhagic lesions in rats treated orally with acidified ethanol. Both, the
      antisecretory effects on gastric acid secretion and the gastric cytoprotective
      effects were less potent compared with the proton pump inhibitor omeprazole. PD
      strongly increased pancreatic secretion, which was substantially inhibited by the
      CCK1 antagonist L-364,718 (but not by the CCK2 antagonist L-365,260). PD also
      showed significant anxiolytic activity as assessed by a black and white box two
      compartment activity assay. Both, time spent in the dark compartment and latency
      for movement from the light to the dark compartment was increased by PD
      (similarly with 5 mg kg(-1) diazepam). In conclusion, PD inhibited gastrin
      stimulated gastric acid secretion, decreased ethanol-induced damage to the
      gastric mucosa, stimulated pancreatic secretion (via CCK1 receptors) and
      displayed anxiolytic activity. Thus, PD may have utility as an adjunct therapy in
      peptic ulcer disease by countering the actions of gastrin and increasing acid
      neutralization and mucosal protection.

PMID- 14577580
TI  - Transport kinetics of zinc, copper, selenium, and iron in perfused human
      placental lobule in vitro.
AB  - Transport characteristics of essential trace elements as zinc, copper, selenium
      and iron have been studied in maternal-fetal direction in normal pregnancies,
      using in vitro perfusion of human placental lobules. Solutions of trace elements
      corresponding to twice the physiological concentrations were injected (100 microl
      bolus) into the maternal arterial perfusate. Serial perfusate samples were
      collected every 30 sec from venous outflows for a study period of 5 min.
      Concentrations of these trace elements and their transport kinetics were
      determined. Transport fractions (TF) of zinc, copper, selenium and iron averaged
      0.21, 0.49, 0.55 and 0.10% of maternal load respectively. Other parameters such
      as area under the curve, clearance, elimination constant, absorption and
      elimination rates showed some significant differences between the various
      elements. Copper and selenium appear to be transported passively in maternal
      fetal direction, while for iron and zinc, role of active transport for transfer
      across the human placental membrane cannot be discounted. We speculate that
      alterations in copper: zinc TR50 (transport rate for 50% efflux) and TF ratios
      could serve as useful indicators for assessing placental transport status of
      these essential elements in complicated pregnancy states.

PMID- 14577581
TI  - Antiprotease effect of anti-inflammatory lupeol esters.
AB  - Lupeol-3-palmitate (LP) and lupeol-3-linoleate (LL), two synthetic long chain
      fatty acid ester analogues of the plant-derived anti-inflammatory pentacyclic
      triterpenoid lupeol (L), were studied in vitro as potential inhibitors of serine
      protease activity. With respect to the natural protein substrate bovine serum
      albumin (BSA), lupeol palmitate and lupeol linoleate inhibited trypsin activity
      in a manner consistent with mixed inhibition (K(IC) values of 103 and 52 microM
      respectively; K(IU) values of 30 and 14 microM respectively). However, the lupeol
      esters showed no inhibitory effect on the catalytic activity of porcine
      pancreatic elastase (PPE) with respect to the synthetic tetrapeptide substrate
      succinyl-(alanyl)3-p-nitroanilide (SAAANA). The present paper shows the lupeol
      triterpenes to be selective protease inhibitors.

PMID- 14577582
TI  - Functional study on baculovirus anti-apoptosis genes.
AB  - Apoptosis of bollworm cell line Hz-AM1 can be delayed by transient expression of
      AcNPV (Autographa californica Nuclear Polihedrosis Virus) p35 gene. Acp35Z, a p35
      inactivated AcNPV by inserting with LacZ gene, cannot replicate in Hz-AM1 cells.
      However, the replication can be rescued by co-transfection with a plasmid
      containing AcNPV p35 gene. It is also realized that the transient expression of
      AcNPV p35 gene in Hela cells can put off cell apoptosis which is induced by
      adding actinomycin-D. Through co-transfection and G418 screening, two anti
      apoptosis cell lines named Sf9-35 and Vero-35 are established by integrating
      AcNPV p35 and Neo expression cassette into the cell chromosomes. The Sf9-35
      enhances the yield of budded virus of AcNPV, while the Vero-35 increases the
      propagation of measles virus.

PMID- 14577583
TI  - Resistance to thapsigargin-induced intracellular calcium mobilization in a
      multidrug resistant tumour cell line.
AB  - A multidrug resistant (MDR) cell line, derived from the human leukaemic cell K562
      and selected for its resistance to Vincristine, was shown to be resistant to
      Thapsigargin (TG). A concentration of 50 nM TG was toxic to K562 cells whereas
      the MDR cell line, known as Lucena I cells, survived unaffected for up to seven
      days in culture. Similarly, no intracellular Ca2+ mobilization was observed in
      the MDR cell line treated with TG. This effect was not a result of TG extrusion
      by P glycoprotein (Pgp), as no mobilization was observed even in the presence of
      the Pgp inhibitors Verapamil (5 microM) and Cyclosporin A (0.16 microM). In the
      present study, both cell lines expressed comparable levels of Bcl-2 making it
      unlikely that Bcl-2 was involved in this process. Similarly, no overexpression of
      the endoplasmic reticulum Ca2+ ATPase (SERCA) could be detected in the MDR cell
      line and Ca2+ uptake by vesicles of the two cell types were equally sensitive to
      TG. These results confirm that MDR cells do not mobilize Ca2+ in the presence of
      TG but go against the possibility that this might be due to TG extrusion or to
      the overexpression of a resistant SERCA isoform.

PMID- 14577585
TI  - Regional variations in intestinal brush border membrane fluidity and function
      during diabetes and the role of oxidative stress and non-enzymatic glycation.
AB  - The physical state (fluidity) of lipids modulates the activities of several
      membrane bound enzymes and transport proteins. Alteration of brush border
      membrane (BBM) fluidity is one of the several changes exhibited by the small
      intestine during diabetes. In the present study, an investigation of the diabetes
      induced regional changes in fluidity, oxidative damage, non-enzymatic glycation
      as well as the activities and the kinetic parameters of the enzymes alkaline
      phosphatase and gamma-glutamyl transpeptidase was carried out on the intestinal
      BBM. At the end of 6 weeks of diabetes, significant increases in the extent of
      both oxidative damage and non-enzymatic glycation were observed along the length
      of the intestine along with a simultaneous decrease in membrane fluidity. A
      significant correlation between the decrease in BBM fluidity and increase in non
      enzymatic glycation was observed in the duodenum and jejunum. Additionally
      regional variations in the activities and kinetic parameters of both the enzymes
      were observed.

PMID- 14577584
TI  - Polymorphism of the p53 codon 72 Arg/Pro and the risk of HPV type 16/18
      associated cervical and oral cancer in India.
AB  - Infection of high risk human papillomaviruses (HPVs) specifically the types 16
      and 18 has been strongly implicated in the development of cervical cancer. The E6
      oncoproteins of these high risk HPVs are known to bind and induce degradation of
      p53 tumour suppressor protein through the ubiquitin pathways. This degradation is
      controlled by a common polymorphism of the p53 gene encoding either a proline or
      an arginine at its codon 72 in exon 4. Recently, it has been demonstrated that
      the presence of homozygous arginine at codon 72 renders p53 about seven times
      more susceptible to E6-mediated proteolytic degradation as well as to cervical
      cancer than those with proline homozygotes or proline/arginine heterozygotes. In
      India, prevalence of HPV as well as cancers of the uterine cervix and the oral
      cavity are highest in the world. We have examined this allele-specific
      predisposition in cervical and oral cancer which is associated with HPV as well
      as in a non-HPV-linked cancer of the breast. We have carried out investigation in
      women comprising whole spectrum of cervical lesions with 128 HPV 16/18 positive
      and 35 HPV negative invasive cervical carcinomas and 34 cases of HPV (16/18)
      positive and 16 HPV negative cervical dysplasias (mild, moderate and severe) and
      104 age-group-matched healthy women as controls. Additionally, we have analysed
      p53Arg-Pro polymorphism in 13 high risk HPV positive and 31 HPV negative oral
      cancers along with 20 normal controls and 77 breast cancers with 41 age-matched
      healthy controls. We observed more than two fold higher risk for homozygous
      arginine (chi2 = 6.3, df = 2, p = 0.04; OR = 2.3; 95% CI: 1.08-5.16) for HPV
      16/18-positive cervical carcinomas when comparison was made only between HPV
      positive cervical cancers and normal controls but most interestingly, no
      significant association either in the frequency of homozygous arginine or proline
      alleles or their heterozygotes could be observed when all the three groups i.e.
      HPV-positive, HPV-negative cervical cancers and controls were considered
      simultaneously. No difference was also observed for either arginine or proline
      polymorphism between women with precancerous lesions of the uterine cervix
      carrying HPV 16/18 infection and controls. Similarly, increased risk of oral or
      breast cancer could not be correlated with the polymorphism of arginine/proline
      allele. Thus the interaction between HPV oncoproteins and the p53 gene
      polymorphism specifically, homozygous arginine at codon 72 appears to play no
      role in the development of either cervical or oral cancer and also it can not
      serve as a biomarker for early identification of cervical, oral or breast cancer.

PMID- 14577586
TI  - Adenosine protects against angiotensin II-induced apoptosis in rat cardiocyte
      cultures.
AB  - Adenosine has been found to be cardioprotective during episodes of cardiac
      ischemia/reperfusion through activation of the A1 and possibly A1 receptors.
      Therefore, we have investigated whether activation of these receptors can protect
      also against apoptotic death induced by angiotensin II (Ang II) in neonatal rat
      cardiomyocyte cultures. Exposure to Ang II (10 nM) resulted in a 3-fold increase
      in programmed cell death (p < 0.05). Pretreatment with the A1 adenosine receptor
      agonist 2-chloro-N6-cyclopentyladenosine (CCPA, 1 microM), abolished the effects
      of Ang II on programmed cardiomyocyte death. Moreover, exposure of cells to the
      A1 adenosine receptor antagonist 8-cyclopentyl- 1,3-dipropylxanthine (CPX) before
      pretreatment with CCPA, prevented the protective effect of the latter.
      Pretreatment with the A3 adenosine receptor agonist N6-(3-iodobenzyl) adenosine
      5'-N-methyluronamide (IB-MECA, 0.1 microM), led to a partial decrease in
      apoptotic rate induced by Ang II. Exposure of myocytes to Ang II caused an
      immediate increase in the concentration of intracellular free Ca2+ that lasted 40
      60 sec. Pretreatment of cells with CCPA or IB-MECA did not block Ang II-induced
      Ca2+ elevation. In conclusion, activation of adenosine A1 receptors can protect
      the cardiac cells from apoptosis induced by Ang II, while activation of the
      adenosine A3 receptors confers partial cardioprotection.

PMID- 14577588
TI  - Flutamide-induced hepatic dysfunction in relation to steady-state plasma
      concentrations of flutamide and its metabolites.
AB  - The frequency, severity, and outcome of flutamide-induced hepatic injury were
      prospectively evaluated in 55 patients with prostate cancer who received 125 mg
      of flutamide 3 times a day (daily dose: 375 mg) combined with an agonistic
      analogue of luteinizing hormone-releasing hormone. In addition, we examined
      plasma and urine concentrations of flutamide and its major metabolites 4 weeks
      after the beginning of flutamide therapy, and evaluated their significance in
      predicting flutamide-induced hepatic dysfunction. Hepatic function could be
      assessed in 50 patients and hepatic dysfunction during therapy was observed in 9
      patients (18%); 3 patients (6%) were classified as having moderate liver
      dysfunction and 6 (12%) were classified as having mild liver dysfunction. The
      steady-state plasma levels of flutamide and its biologic active metabolite,
      hydroxyflutamide (OH-Flu), were not related to hepatic dysfunction. However, the
      concentration of another major metabolite, 4-nitro-3-(trifluoromethyl)phenylamine
      (FLU-1) was considerably higher in 2 patients who developed clinically
      significant hepatic dysfunction. These findings suggest that clinically
      significant hepatic dysfunction could be induced in patients with compromised
      flutamide metabolism, which leads to a high concentration of FLU-1. Based on
      results of this study, we propose that plasma FLU-1 levels are one of the
      predictive factors for flutamide-induced hepatic dysfunction. This hypothesis
      will be confirmed in a large-scale study.

PMID- 14577587
TI  - Dietary G-rutin suppresses glycation in tissue proteins of streptozotocin-induced
      diabetic rats.
AB  - The present study focused on examining the efficacy of feeding a rutin-glucose
      derivative (G-rutin) to inhibit glycation reactions that can occur in muscle,
      kidney and plasma proteins of diabetic rats. Both thiobarbituric acid-reactive
      substance levels and protein carbonyl contents in muscle and kidney were
      significantly (p < 0.05) reduced in streptozotocin-induced diabetic rats fed G
      rutin supplemented diet, compared to diabetic rats fed control diet. The
      N(epsilon)-fructoselysine content in muscle and kidney, a biomarker of early
      glycation reaction, was markedly (p < 0.05) increased by diabetes, but
      significantly (p < 0.05) reduced in diabetic rats fed G-rutin. Advanced glycation
      end-products (AGEs) in serum and kidney protein were measured by immunoblot using
      anti-AGE antibody, and were also reduced in diabetic rats fed dietary G-rutin.
      Feeding G-rutin also slightly inhibited aldose reductase activity in these
      animals. These results demonstrate for the first time that dietary G-rutin
      consumption can provide potential health benefits that are related to the
      inhibition of tissue glycation reactions common to diabetes.

PMID- 14577589
TI  - Expression and characterization of Asp fI, an immunodominant allergen/antigen of
      A. fumigatus in insect cell.
AB  - Asp fI is a major allergen/antigen/cytotoxin of Aspergillus fumigatus and
      exhibits ribonuclease activity. This allergen plays a role in allergic and
      invasive Aspergillosis and reported as a major cytotoxin with ribonuclease
      activity. To express the protein in large quantity and to characterize the
      multifunctional nature of Asp fI, we have generated recombinant baculovirus by
      introducing the gene in pFastBac HTa expression vector and expressed in insect
      cell. The baculovirus expression vector system has been used as a versatile
      system for the efficient expression of proteins with most eukaryotic
      posttranslational modification. Recombinant Asp fI was expressed as approximately
      1% of the total cellular protein in infected Sf9 insect cells. The protein was
      purified using Ni2+ affinity column chromatography and the yield of purified
      protein was approximately 10 mg/l g of total cellular protein. Immunoreactivity
      of the protein was determined by immunoblot analysis using both poly His
      monoclonal antibody, IgG and IgE antibodies present in the sera of ABPA patients.
      The protein was glycosylated as revealed by the glycoprotein staining and was
      observed to retain both ribonuclease and cytotoxic activities. These results
      suggest that Asp fI expressed in insect cell was post translationally modified
      and biologically active that can be used as a diagnostic marker for biochemical
      studies.

PMID- 14577590
TI  - Vitamin A metabolism in cultured somatic cells from rat testis.
AB  - Sertoli and peritubular myoid cells, the somatic cells of the seminiferous
      tubule, support growth and differentiation of developing germ cells. This action
      strictly depends on the availability of in situ synthesized retinoic acid and we
      have previously documented the ability of Sertoli, but not peritubular cell
      extracts, to support the oxidation of retinol to retinoic acid. Using primary
      cultures of somatic cells treated with a physiological concentration of free
      retinol, we show here that the same is essentially true also for whole cultured
      cells. Sertoli cells are capable of producing not only retinoic acid, but are
      also the major site of retinyl ester (mainly, retinyl palmitate) formation.
      Compared with retinyl palmitate accumulation, retinoic acid synthesis was both
      faster and positively influenced by prior exposure to retinol. This increase in
      retinoic acid synthesis was further augmented by treatment with the retinoic acid
      catabolic inhibitor liarozole, thus indicating that enhanced synthesis, rather
      than reduced catabolism, is responsible for such an effect. Myoid cells had a
      higher capacity to incorporate exogenously supplied retinol, yet retinoic acid
      synthesis, and even more so retinyl palmitate formation, were considerably lower
      than in Sertoli cells. Retinoic acid synthesis in myoid cells was not only
      depressed, but also very little influenced by prior retinol exposure and totally
      insensitive to liarozole. These data further support the view that myoid cells
      are involved in retinol uptake from the blood and its transfer to other cells,
      rather than in metabolic interconversion or long-term storage of vitamin A, two
      processes that mainly take place in Sertoli cells.

PMID- 14577591
TI  - Alterations in myocardial ultrastructure and protein expression after a single
      injection of isoproterenol.
AB  - Immunochemical and electron microscopic characterization of rat myocardium was
      conducted 2 h and 3 weeks after a single injection of isoproterenol in rats. The
      relative content of several myospecific proteins (KRP--kinase-related protein,
      desmin), cytoskeletal proteins (tubulin, vinculin, myosin light chain kinase-
      MLCK) and extracellular matrix protein fibronectin was determined by
      immunoblotting. Two hours after injection of 50 mg/kg isoproterenol a destruction
      of some cardiomyocytes, contracture of myofibrils and mild edema of intercellular
      space was observed. The content of all the studied proteins except KRP decreased
      below control levels. This situation sustained 3 weeks after injection and
      paralleled alterations in cardiomyocyte ultrastructure. Areas of myofibrillar
      contracture and lysis were noted, glycogen granules were sparse; mitochondria
      contained arrow-like inclusions that are characteristic for calcium overload,
      also huge mitochondria contacting each other by specialized intermitochondrial
      contacts were detected. Clumps of unripe elastic fibers in enlarged intercellular
      space were combined with increased deposition of collagens type I and III forming
      areas of fibrosis. The smaller dosage of isoproterenol (10 mg/kg) rendered no
      significant damage in the acute postinjection period but 3 weeks later it induced
      the thickening of extracellular matrix around cardiac cells and the increase in
      KRP and tubulin content by 26 and 32%, correspondingly. MLCK levels remained
      depressed throughout the experiment. The rise in KRP expression was also observed
      after the addition of isoproterenol to cultured chicken embryo cardiomyocytes.
      Obtained results indicate that even a single injection of isoproterenol creates
      long lasting structural alterations in cardiac muscle accompanied by the
      increased expression of extracellular matrix proteins and several sarcoplasmic
      proteins apparently involved in hypertrophic response of cardiomyocytes.

PMID- 14577592
TI  - Biochemical characterization of Ca2+/calmodulin dependent protein kinase from
      Candida albicans.
AB  - A multifunctional Ca2+/calmodulin dependent protein kinase was purified
      approximately 650 fold from cytosolic extract of Candida albicans. The purified
      preparation gave a single band of 69 kDa on sodium dodecyl sulfate polyacrylamide
      gel electrophoresis with its native molecular mass of 71 kDa suggesting that the
      enzyme is monomeric. Its activity was dependent on calcium, calmodulin and ATP
      when measured at saturating histone IIs concentration. The purified Ca2+/CaMPK
      was found to be autophosphorylated at serine residue(s) in the presence of
      Ca2+/calmodulin and enzyme stimulation was strongly inhibited by W-7 (CaM
      antagonist) and KN-62 (Ca2+/CaM dependent PK inhibitor). These results confirm
      that the purified enzyme is Ca2+/CaM dependent protein kinase of Candida
      albicans. The enzyme phosphorylated a number of exogenous and endogenous
      substrates in a Ca2+/calmodulin dependent manner suggesting that the enzyme is a
      multifunctional Ca2+/calmodulin-dependent protein kinase of Candida albicans.

PMID- 14577593
TI  - Alterations in aortic antioxidant components in an experimental model of
      atherosclerosis: a time-course study.
AB  - Antioxidant component alterations in the aorta during atherogenesis were examined
      in atherosclerosis-susceptible (SUS) Japanese quail fed a cholesterol
      supplemented (0.5% w/w) diet. Birds fed a non-supplemented diet provided
      information on the effects of aging on endogenous antioxidants. One hundred adult
      SUS males were used. Birds were sacrificed after 0, 4, 8 and 12 weeks on the
      diets and were examined for plaque development and corresponding antioxidant
      component alterations in aorta and myocardium. With aging, superoxide dismutase
      (SOD) activity was increased in both tissues, whereas aortic glutathione
      peroxidase (GPx) activity and myocardial glutathione reductase (GRd) activity
      decreased. Myocardial ascorbate levels increased with aging, with a reciprocal
      decrease in myocardial tocopherol levels. Following 4 weeks of cholesterol
      supplementation, aortic GRd decreased, SOD activity increased, but activities of
      GPx and catalase were unchanged. This same qualitative pattern of antioxidant
      enzyme changes was also found in myocardium. Thus, although aortic antioxidant
      enzyme changes produced by cholesterol feeding and aging showed some
      similarities, the early phase of atherogenesis does not simply reflect
      accelerated aging. In the late stages of atherogenesis, SOD activity returned to
      baseline, but other antioxidant enzymes remained unaltered from levels
      characterizing the early phase of lesion development. There was no detectable
      functional coupling between changes in GPx and GRd, nor between SOD (which
      produces hydrogen peroxide) and GPx or catalase (which utilize hydrogen peroxide
      as substrate). Previously reported alterations in erythrocyte antioxidant enzyme
      components during atherogenesis in quail were not predictive of changes in the
      corresponding enzymes in the aorta and myocardium.

PMID- 14577594
TI  - Effects of phosphodiesterase 3,4,5 inhibitors on hepatocyte cAMP levels,
      glycogenolysis, gluconeogenesis and susceptibility to a mitochondrial toxin.
AB  - Various phosphodiesterase (PDE) 3,4 and 5 inhibitors have been compared with
      glucagon for their effectiveness at increasing hepatocyte cAMP, glycogenolysis
      and gluconeogenesis. Preincubation of isolated hepatocytes with PDE 3 and 4
      inhibitors (50 microM) for 2 h induced significant increases in cellular cAMP
      level. The order of effectiveness was: glucagon (78%), V11294A (42%), rolipram
      (40%), milrinone (36%), CDP-840 (33%), R(0) 20-1724 (31%), papaverine (27%),
      isobutylmethylxanthine (28%), isoliquiritigenin (25%), theophylline (22%), and
      amrinone (22%). The PDE 5 inhibitors dipyridamol and sildenafil had only a slight
      effect on cAMP levels. Glucose formation was increased as a result of increased
      glycogenolysis in the following order of effectiveness: glucagon (89%), V11294A
      (63%), rolipram (61%), milrinone (50%), CDP-840 (46%), R(0) 20-1724 (45%),
      sildenafil (34%), dipyridamol (31%), papaverine (30%), isobutylmethylxanthine
      (29%), theophylline (20%), amrinone (20%), and isoliquiritigenin (20%). Rolipram
      and milrinone, selective PDE 4 and PDE 3 inhibitors respectively, stimulated the
      gluconeogenesis of alanine, lactate + pyruvate, or fructose in hepatocytes
      isolated from fasted rats. On the other hand, selective cGMP specific
      phospodiesterase inhibitors, sildenafil and dipyridamol inhibited alanine-induced
      gluconeogenesis. All PDE inhibitors increased hepatocyte susceptibility to
      cyanide toxicity (3-4 fold) which was prevented by fructose whereas PDE 5
      inhibitors did not significantly increase hepatocyte susceptibility.

PMID- 14577595
TI  - Membrane-bound alkaline phosphatase gene induces antitumor effect by G2/M arrest
      in etoposide phosphate-treated cancer cells.
AB  - Gene therapy is used to induce immune responses, regulate tumor growth, or
      sensitize tumor cells to specific treatment. For sensitizing tumor cells to
      specific drug, we considered a prodrug-converting system using membrane-bound
      intestinal alkaline phosphatase (IAP) as the prodrug-activating genes. The IAP is
      capable of converting a relatively non-cytotoxic prodrug, etoposide phosphate
      (EP), into etoposide with a significant antitumor activity. We used the
      retroviral vector for transducing IAP gene into SNU638 gastric cancer cells and
      EP was prepared by phosphorylation of etoposide. To determine the chromosomal
      incorporation of membrane-bound IAP gene and AP activity in IAP gene-transduced
      cells (SNU638/IAP), we performed genomic PCR and AP activity analysis. In genomic
      DNA of SNU638/IAP cells, full cDNA fragment of a 2.5 kb IAP was detected, and AP
      activity was shown at most 15 approximately 18-fold increase compared with
      control cells. According to the in vitro cytotoxicity study, SNU638/IAP cells
      greatly enhanced the cytotoxic effect in proportion to the concentration of EP,
      while control cells didn't cause any cytotoxic effects after EPtreatment.
      Especially, the cell population of G2/M phase was increased in EP-treated SNU638/
      IAP cells because P4 DNA unknotting activity of topoisomerase II was decreased by
      EP treatment such as the action mechanism of etoposide. Finally, a strong
      antitumor response was observed in SNU638/IAP cancer cells-bearing nude mice that
      were treated with EP. These results suggest that the prodrug-converting system by
      membrane-bound IAP gene and EP prodrug is useful as the strong strategy of gene
      therapy for cancer treatment.

PMID- 14577596
TI  - Gene expression profiling during thymus ontogeny and its association with
      TCRVbeta8.1-Dbeta2.1 rearrangements of inbred mouse strains.
AB  - The V(D)J recombination of TCRalpha and beta in early developing T-cells is a
      highly modulated phenomenon initiated and completed by recombinase complex (RAG-1
      and RAG-2), and regulated by other gene products such as interleukins. To further
      evaluate the association of several other gene products with the evolution of
      TCRVbeta8.1 V(D)J rearrangements in vivo, the mRNA expression levels of seven
      interleukins, three cytokines, receptors TCRVbeta8.1 and IL-2Rbeta, MHC-I/MHC-II,
      RAG-1/ RAG-2 and retroviral superantigen MMTV(SW) were measured by RT-PCR during
      the fetal development of the thymus of three inbred mouse strains (Balb-c,
      C57B1/6 and CBA/J). Clustering using the Tree View software, was used to organize
      these genes based on similarity of expression patterns. Each strain displayed a
      different expression profile during thymus ontogeny. During the late
      developmental stage the most evident association was the kinetics of MMTV(SW)
      retrovirus, IL-2Rbeta and IL-7 overexpression with reduction of TCRVbeta8.1
      D1beta2.1 rearrangement in the thymus of CBA/J mice. These data suggest a
      susceptibility of this strain to expression of MMTV(SW) upon reduction of the
      rearranged TCRVbeta8.1-Dbeta2.1 segment in developing thymocytes, with parallel
      IL-7 overexpression.

PMID- 14577598
TI  - Phospholamban phosphorylation in ischemia-reperfused heart. Effect of pacing
      during ischemia and response to a beta-adrenergic challenge.
AB  - The status of phospholamban (PLB) phosphorylation in the ischemia-reperfused
      hearts remains controversial. Although a decrease in the phosphorylation of both
      PLB residues (Ser16, PKA site, and Thr17, CaMKII site) was previously reported,
      experiments from our laboratory failed to detect this decrease. In an attempt to
      elucidate the cause for this discrepancy, experiments were performed in
      Langendorff-perfused rat hearts with two main goals: (1) To determine whether
      keeping pacing during ischemia, a protocol followed in other ischemia-reperfusion
      models, decreases the phosphorylation of PLB residues, below pre-ischemic values;
      (2) To investigate whether a maximal beta-adrenergic challenge allows to detect a
      decrease in the ability of PLB to be phosphorylated in ischemia-reperfused
      hearts. Hearts were submitted to a global ischemia/reperfusion protocol (20/30
      min) with (P) or without (NP) pacing during ischemia, and phosphorylation of PLB
      residues was assessed by immunodetection. The recovery of contractility upon
      reperfusion was lower in P vs. NP hearts. Ser16 of PLB, was phosphorylated at the
      end of ischemia in NP hearts. This increase appeared earlier in P hearts and was
      significantly diminished by catecholamine depletion and beta-blockade. Thr17 site
      was phosphorylated at the beginning of ischemia and the onset of reperfusion. The
      ischemia-induced phosphorylation of Thr17 was higher and more sustained in P vs.
      NP hearts, and inhibited by the calcium channel blocker, nifedipine, whereas the
      reperfusion-induced increase in Thr17 phosphorylation was similar in P and NP
      hearts and was significantly diminished by the Na+/Ca2+ exchanger inhibitor KB
      R7943. Phosphorylation of PLB residues did not decrease below basal levels at any
      time during ischemia and reperfusion. However, the phosphorylation, inotropic and
      lusitropic response to beta-adrenergic stimulation was significantly decreased
      both in P and NP hearts.

PMID- 14577597
TI  - Norepinephrine-induced cardiac hypertrophy and fibrosis are not due to mast cell
      degranulation.
AB  - The norepinephrine (NE)-induced hypertrophy of the left ventricle (LV) in the rat
      is preceded by increased interleukin (IL)-6 expression and associated with LV
      fibrosis. We have examined whether the elevated level of IL-6 may be due to mast
      cell degranulation. Therefore we tested the effect of cromoglycate sodium salt
      (cromolyn), an inhibitor of mast cell degranulation with anti-inflammatory and
      membrane-stabilizing activity, on the increased expression of IL-6 mRNA and of
      mRNAs of proteins involved in the remodelling of the extracellular matrix (ECM)
      which is induced by NE (0.1 mg/kg x h). After 4 h, the NE-induced increase in IL
      6 mRNA expression was not influenced by cromolyn (20 mg/kg x h). Cromolyn
      infusion for 3 days did not affect the extent of LV hypertrophy induced by NE, as
      measured by the LV weight/body weight (LVW/BW) ratio and by atrial natriuretic
      peptide (ANP) expression. Cromolyn induced a slight depression of the NE-induced
      elevation of the matrix metalloproteinase (MMP)-2. However, it did not affect the
      NE-induced elevated levels of mRNAs of collagen I and III and the tissue
      inhibitor of matrix metalloproteinase (TIMP)-2. Since cromolyn did not reduce the
      NE-effects in rat hearts in vivo we conclude that mast cell degranulation seems
      not to be involved in them.

PMID- 14577599
TI  - Labelling of lipids by D-[1-14C]glucose, D-[6-14C] glucose and D-[3-3H]glucose in
      pancreatic islets from normal and GK rats.
AB  - In pancreatic islets prepared from either normal or GK rats and incubated at
      either low (2.8 mM) or high (16.7 mM) D-glucose concentration, the labelling of
      both lipids and their glycerol moiety is higher in the presence of D-[1
      14C]glucose than D-[6-14C]glucose. The rise in D-glucose concentration augments
      the labelling of lipids, the paired 14C/3H ratio found in islets exposed to both
      D-[1-14C]glucose or D-[6-14C]glucose and D-[3-3H]glucose being even slightly
      higher at 16.7 mM D-glucose than that found, under otherwise identical
      conditions, at 2.8 mM D-glucose. Such a paired ratio exceeds unity in islets
      exposed to D-[1-14C]glucose. The labelling of islet lipids by D-[6-14C]glucose is
      about 30 times lower than the generation of acidic metabolites from the same
      tracer. These findings indicate (i) that the labelling of islet lipids accounts
      for only a minor fraction of D-glucose catabolism in pancreatic islets, (ii) a
      greater escape to L-glycerol-3-phosphate of glycerone-3-phosphate generated from
      the C1-C2-C3 moiety of D-glucose than D-glyceraldehyde-3-phosphate produced from
      the C4-C5-C6 moiety of the hexose, (iii) that only a limited amount of [3
      3H]glycerone 3-phosphate generated from D-[3-3H]glucose is detritiated at the
      triose phosphate isomerase level before being converted to L-glycerol-3
      phosphate, and (iv) that a rise in D-glucose concentration results in an
      increased labelling of islet lipids, this phenomenon being somewhat more
      pronounced in the case of D-[1-14C]glucose or D-[6-14C]glucose rather than D-[3
      3H]glucose.

PMID- 14577600
TI  - Heme oxygenase and antioxidant status in cultured aortic endothelial cells
      isolated from atherosclerosis-susceptible and -resistant Japanese quail.
AB  - We have investigated heme oxygenase (HO) and antioxidant status in the novel
      isolation and characterization of aortic endothelial cells (AECs) from a random
      bred wild-type strain (WILD) and selectively bred atherosclerosis-susceptible
      (SUS) and -resistant (RES) strains of Japanese quail. Cultured AECs expressed
      acetylated LDL, and were probed with endothelial and smooth muscle cell specific
      antibodies to confirm purity of culture. Subconfluent monolayers of RES AECs had
      higher HO activity than SUS AECs. At confluence, HO activity levels were similar
      among strains. However, RES AECs had higher HO-1 protein than WILD and SUS cells.
      Although ferritin protein levels were similar among the three strains, catalytic
      iron was higher in SUS AECs than WILD and RES cells. Glutathione levels were
      highest in SUS cells, intermediate in WILD, and lowest in RES, while glutathione
      reductase was higher in WILD and RES AECs than SUS AECs. We suggest that
      differences in atherosclerosis susceptibility between RES and SUS may be due, at
      least in part, to differences in endothelial HO and antioxidant components.

PMID- 14577601
TI  - Atrial natriuretic hormone prohormone gene expression in cardiac and extra
      cardiac tissues of diabetic Goto-Kakizaki rats.
AB  - The present investigation was designed to determine if the mechanism for the
      increased atrial natriuretic peptides within the circulation of diabetic animals
      involves atrial natriuretic hormone prohormone (proANH) gene expression
      upregulation. The tissue specificity of this potential upregulation of the proANH
      gene was investigated in a spontaneous model of type 2 diabetes, i.e. the Goto
      Kakizaki (GK) rat with comparison to age-matched non-diabetic Wistar rats from
      which the GK colony was originally derived. Reverse transcription-polymerase
      chain reaction revealed that proANH gene expression was increased 3.1-fold in the
      left heart ventricle, 5-fold in lung, 2-fold in kidney, 3-fold within mucosa and
      1.8-fold within muscle of gastric antrum (p < 0.05 for each) of GK rats compared
      to Wistar rats. There was no significant increase in proANH gene expression in
      atria and right ventricle of the heart of GK rats compared to Wistars. These
      results indicate that steady-state ANH prohormone mRNA levels increase within the
      left ventricle and extracardiac tissues in type 2 diabetic animals. This enhanced
      gene expression is a functional increase with its expressed proteins (4 peptide
      hormones; ANPs) increasing 2-6 fold within the circulation of GKs. The greater
      increase in proANH messenger RNA in the extracardiac tissues compared to the
      amount of increase within the heart and the greater tissue mass of these combined
      extra cardiac tissues suggests the majority of the increase in ANPs within the
      circulation of diabetics is secondary to increased synthesis in extracardiac
      tissues. This also suggests that there is a systemic regulatory mechanism of
      proANH gene expression not only within the heart but also within the lung,
      gastrointestinal tract and kidney. Diabetes is the first disease in which there
      is more upregulation of ANH prohormone in extracardiac tissues compared to
      upregulation within the heart itself.

PMID- 14577602
TI  - Thermally induced disintegration of the oligomeric structure of alphaB-crystallin
      mutant F28S is associated with diminished chaperone activity.
AB  - alphaB-crystallin, a member of the small heat-shock protein (hsp) family of
      proteins, is able to function as a molecular chaperone by protecting other
      proteins from stress-induced aggregation by recognizing and binding to partially
      unfolded species of damaged proteins. The present work has investigated the role
      of phenylalanine-28 (F28) of the 22RLFDQFF28 region of alphaB-crystallin in
      maintaining chaperone function and oligomeric structure under physiological
      condition and under thermal stress. Bovine alphaB-crystallin was cloned for the
      first time and the cDNA sequence revealed greater than 90% homology to that of
      human, rat and mouse alphaB-crystallins. F28 was mutated to a serine followed by
      expression of the mutant F28S and the wild-type alphaB (alphaB-wt) in E. coli and
      subsequent purification of the protein by size-exclusion chromatography.
      Secondary and tertiary structure analyses showed some structural changes in the
      mutant. Chaperone activity and oligomeric size of the mutant was unchanged at 37
      degrees C whereas at 58 degrees C the chaperone activity was significantly
      decreased and the oligomeric size ranged from low molecular weight to high
      molecular weight showing disintegration of the oligomeric structure. The data
      support the idea that the participation of large oligomeric structure rather than
      smaller units is required to have optimal chaperone activity and the hydrophobic
      F28 residue is needed for maintaining the native oligomeric structure under
      thermal stress.

PMID- 14577603
TI  - Two novel spliced presenilin 2 transcripts in human lymphocyte with oxidant
      stress and brain.
AB  - We identified two novel spliced human presenilin 2 (PS2) transcripts. The first,
      PS2deltaEx3-7, lacked part ofexon 3, all of exons 4, 5, and 6, and part of exon
      7, resulting in an in-frame shift and inclusion of the natural start codon and
      proteolytic region. This transcript was detected in cerebral cortex and
      peripheral lymphocytes. The second transcript, PS2deltaEx4, lacked exon 4,
      resulting in a frame shift and inclusion of the natural start codon, and was
      transcribed in peripheral lymphocytes and heart but not in brain. Quantitative RT
      PCR analysis revealed that the PS2deltaEx3-7 significantly increased in
      lymphocytes treated with H2O2, suggesting that this transcript is a novel genetic
      marker that can be used to study the pathogenesis of Alzheimer's disease.

PMID- 14577604
TI  - Inhibition of the group I ribozyme splicing by NADP+.
AB  - The coenzyme NADP+ (nicotinamide adenine dinucleotide phosphate) and its analogs
      were tested for inhibition of the self-splicing of primary transcripts of the
      phage T4 thymidylate synthase gene (td). Of all compounds examined, the 3'-NADP
      was the most potent inhibitor and the order of inhibitory efficiency for
      compounds tested was as follows: 3'-NADP+ > NADP+ > NADP(+)-dialdehyde > NADPH >
      1,N6-etheno-NADP+. Increasing guanosine concentration up to 40 microM overcame
      the suppression of self-splicing by NADP+ up to 76% of the level of normal
      splicing but didn't recover the full splicing activity. Similarly, Mg2+ also
      served to restore the splicing activity by about 90% at 25 mM concentration above
      which the splicing started to decline. The kinetic analysis showed that NADP+
      acts as a mixed type non-competitive inhibitor for the td intron RNA with a Ki of
      4.1 mM. The specificity of the splicing inhibition by NADP+ is predominantly due
      to increases in Km and decreases in kcat values. The results indicate that the
      inhibition by NADP+ was guanosine and Mg2+ dependent.

PMID- 14577605
TI  - Effect of hypo- and hyperthyroid states on phospholipid composition in developing
      rat heart.
AB  - The aim of this study was to examine the effect of hypo- and hyperthyroidism on
      the phospholipid composition in developing rat heart. The hypothyroid state (PTU)
      was induced by 0.05% 6-n-propyl-2-thiouracil in drinking water given to nursing
      mothers from the postnatal day 2-21. The hyperthyroidism (T3) was made by daily
      injection of 3,3',5-triiodo-L-thyronine (10 microg/100 g body wt) to newborns in
      the same time period. Age matched intact littermates were taken as euthyroid
      controls. PTU decreased the concentration of total phospholipids (PL), choline
      phosphoglycerides (PC), ethanolamine phosphoglycerides (PE) and
      diphosphatidylglycerol (DPG) and increased the proportion of plasmalogen
      component of PE (PLPE). T3 increased the concentration of PL, PC, PE, DPG and
      decreased PLPE in comparison with euthyroid controls. The ratio of
      saturated/unsaturated fatty acids (FA) in PE was decreased in PTU and increased
      in T3 group. The ratio of n-6/n-3 polyunsaturated FA in PC, PE and
      phosphatidylinositol (PI) was increased in PTU due to increase of 18:2n-6 and
      decrease of 22:6n-3 proportion. T3 decreased this ratio because of decline in
      20:4n-6 and rise in 22:6n-3 proportion. Both hypo- and hyperthyroidism decreased
      the ratio of 20:4n-6/18:2n-6 in the majority of phospholipids. PTU decreased the
      unsaturation index in PC, PI and phosphatidylserine. It is concluded that thyroid
      state plays an essential role in the development of membrane phospholipid
      components in cardiac membranes during the early postnatal period.

PMID- 14577607
TI  - Metabolism, not autoxidation, plays a role in alpha-oxoaldehyde- and reducing
      sugar-induced erythrocyte GSH depletion: relevance for diabetes mellitus.
AB  - Erythrocyte and lens reduced glutathione (GSH) levels are often lower in patients
      with diabetes whereas erythrocyte dicarbonyl levels are often higher. We
      hypothesise that high plasma carbohydrates may be metabolised by glycolytic and
      pentose phosphate pathways to form alpha-oxoaldehydes, which deplete cellular
      GSH. Our aims were: (1) to compare the effectiveness of various carbohydrates or
      metabolites at depleting erythrocyte GSH, (2) to determine if GSH loss is related
      to the autoxidation or metabolism of carbohydrates. It was found that erythrocyte
      GSH was depleted by 50% (ED-50) at t = 2.5 h when erythrocytes were incubated
      with the following: methylglyoxal (MG) 23 microM, glyoxal 75 microM, DL
      glyceraldehyde 299 microM, deoxyribose 606 microM, xylitol 626 microM, and ribose
      2 mM. The glycolytic inhibitors, sodium arsenate and KF prevented ribose,
      deoxyribose, xylitol and MG-induced GSH depletion in erythrocytes over 2 h.
      However, the antioxidant trolox and the ferric chelator detapac did not affect MG
      induced GSH depletion. These data suggest that the carbohydrates or
      glyceraldehyde were metabolised to form carbonyls such as MG which depleted
      erythrocyte GSH as a result of catalysis by glyoxalase I. None of the
      carbohydrates were autoxidised to carbonyls over this time period. We speculate
      that as a result of GSH depletion, subsequent glycoxidative stress affects
      erythrocyte function and contributes to diabetic complications.

PMID- 14577608
TI  - Implication of adenosine 3',5'-cyclic monophosphate, guanosine 3',5'-cyclic
      monophosphate, adenosine 5'-mono-, di-, and triphosphate and fructose-2,6
      bisphosphate in the regulation of the glycolytic pathway in relation to the
      gametogenic cycle in the mussel mytilus galloprovincialis Lmk.
AB  - The changes in the contents of cyclic AMP, cyclic GMP, ATP, ADP, AMP and fructose
      2,6-bisphosphate that occur in the mantle tissue of the mussel Mytilus
      galloprovincialis Lmk were analysed with regard to the annual gametogenic cycle.
      Throughout 2 years, the lowest contents of AMP, ADP and ATP were detected during
      late winter-spring, whereas the maximum appeared in the autumn months. During the
      second year, fructose-2,6-bisphosphate and cAMP showed a very similar behaviour.
      The levels of both compounds rose throughout the year until a maximum in
      September. Their behaviour was also similar to that observed during the first
      year, but displaced in time. Both in 1998 and in 1999, the highest level of cGMP
      was detected during the spring-summer months. The results obtained suggest that
      the glycolytic pathway, with regard to the breeding cycle, might be regulated by
      fructose-2,6-bisphosphate and cyclic AMP through the activation of 6
      phosphofructo-1-kinase, which is the main regulating enzyme of the glycolysis in
      mantle of M. galloprovincialis.

PMID- 14577609
TI  - S-nitrosothiol detection in isolated perfused rat heart.
AB  - Nitrogen monoxide (NO) has important cardiovascular actions, and it has been
      suggested that they may be partly mediated by the reaction with protein
      sulfhydryl groups to produce S-nitrosothiols. In this work we describe and test a
      method that allows S-nitrosothiol detection in crude membrane preparations
      obtained from isolated perfused rat hearts. Isolated rat hearts were perfused
      under control conditions or in the presence of the NO donors SIN-1 and isosorbide
      dinitrate. Additional hearts were subjected to 10-20 min of ischemia followed or
      not by 10-20 min of reperfusion. At the end of perfusion a crude membrane
      fraction was prepared, and S-nitrosothiol concentration was assayed
      fluorometrically, on the basis of 2,3-naphthotriazole production from 2,3
      diaminonaphthylene. The sensitivity of the method, as evaluated using S
      nitrosoalbumin, was on the order of 1-2 pmol/mg of protein. S-nitrosothiols were
      undetectable under control conditions, as well as after ischemia or ischemia
      reperfusion. On the other hand, significant S-nitrosothiol formation was observed
      after infusion of SIN-1 or isosorbide dinitrate (26.4 +/- 7.4 and 19.9 +/- 5.6
      pmol per mg of protein, respectively). In conclusion, S-nitrosothiol production
      was observed in rat heart membranes after exposure to NO donors, while S
      nitrosothiol concentration was below the sensitivity limits of the assay either
      under baseline conditions or after acute ischemia and reperfusion.

PMID- 14577606
TI  - Clinical implications of matrix metalloproteinases.
AB  - Matrix metalloproteinases (MMPs) are a family of neutral proteinases that are
      important for normal development, wound healing, and a wide variety of
      pathological processes, including the spread of metastatic cancer cells,
      arthritic destruction of joints, atherosclerosis, pulmonary fibrosis, emphysema
      and neuroinflammation. In the central nervous system (CNS), MMPs have been shown
      to degrade components of the basal lamina, leading to disruption of the blood
      brain barrier and to contribute to the neuroinflammatory responses in many
      neurological diseases. Inhibition of MMPs have been shown to prevent progression
      of these diseases. Currently, certain MMP inhibitors have entered into clinical
      trials. A goal to the future should be to design selective synthetic inhibitors
      of MMPs that have minimum side effects. MMP inhibitors are designed in such a way
      that these can not only bind at the active site of the proteinases but also to
      have the characteristics to bind to other sites of MMPs which might be a
      promising route for therapy. To name a few: catechins, a component isolated from
      green tea; and Novastal, derived from extracts of shark cartilage are currently
      in clinical trials for the treatment of MMP-mediated diseases.

PMID- 14577610
TI  - Oxidant-induced pHi/Ca2+ changes in rat aortic smooth muscle cells. The role of
      atrial natriuretic peptide.
AB  - The aim of this study was to investigate the effects of oxidative stress on PLD
      activity, [Ca2+]i and pHi levels and the possible relationship among them.
      Moreover, since atrial natriuretic peptide (ANP) protects against oxidant-induced
      injury, we investigated the potential protective role of the hormone in rat
      aortic smooth muscle (RASM) cells exposed to oxidative stress. Water-soluble 2,2'
      Azobis (2-amidinopropane) dihydrochloride (AAPH) was used as free radical
      generating system, since it generates peroxyl radicals with defined reaction and
      the half time of peroxyl radicals is longer than other ROS. A significant
      increase of PLD activity was related to a significant decrease in pHi, while
      [Ca2+]i levels showed an increase followed by a decrease after cell exposure to
      AAPH. [Ca2+]i changes and pHi fall induced by AAPH were prevented by cadmium
      which inhibits a plasma membrane Ca2+ ATPase coupled to Ca2+/H+ exchanger, that
      operates the efflux of Ca2+ coupled to H+ influx. The involvement of PLD in pHi
      and [Ca2+]i changes was confirmed by calphostin-c treatment, a potent inhibitor
      of PLD, which abolished all AAPH-induced effects. Pretreatment of RASM cells with
      pharmacological concentrations of ANP attenuated the AAPH effects on PLD activity
      as well as [Ca2+]i and pHi changes, while no effects were observed with
      physiological ANP concentrations, suggesting a possible role of the hormone as
      defensive effector against early events of the oxidative stress.

PMID- 14577611
TI  - AMP-deaminase from human term placenta.
AB  - AMP-deaminase from human term placenta was chromatographed on a phosphocellulose
      column and physico-chemical and immunological properties of the purified enzyme
      were investigated. At physiological pH 7.0, in the absence of regulatory ligands
      (control conditions) studied AMP-deaminase manifested sigmoid-shaped substrate
      saturation kinetics, with half-saturation parameter (S0.5) value of about 7 mM.
      Addition of important allosteric effectors (ATP, ADP or orthophosphate) modified
      kinetic properties of studied AMP-deaminase, influencing mainly the value of
      S0.5, parameter. Micromolar concentrations of stearylo-CoA inhibited potently the
      enzyme making it no longer sensitive towards 1 mM ATP-induced activation. SDS
      PAGE electrophoresis of the purified enzyme revealed presence of 68 kDa protein
      fragment, reacting with anti-(human) liver AMP-deaminase antibodies. Experimental
      results presented indicate that 'liver type' of AMP-deaminase is an enzyme form
      present in human term placenta.

PMID- 14577612
TI  - Effects of niacin-bound chromium, Maitake mushroom fraction SX and (-)
      hydroxycitric acid on the metabolic syndrome in aged diabetic Zucker fatty rats.
AB  - Previous studies in our laboratories have demonstrated that niacin-bound chromium
      (NBC), Maitake mushroom and (-)-hydroxycitric acid (HCA-SX) can ameliorate
      hypertension, dyslipidemias and diabetes mellitus, and therefore may be useful in
      weight management. In the present study, we used aged, diabetic Zucker fatty rats
      (ZFR) (70-75 weeks) in order to determine whether NBC, fraction SX of Maitake
      mushroom (MSX) and 60% (-)-hydroxycitric acid (HCA-SX) from Garcinia cambogia,
      alone or in combination, can affect certain aspects of the metabolic syndrome.
      Syndrome X or metabolic syndrome has been described as a concurrence of disturbed
      glucose and insulin metabolism, overweight and abdominal fat distribution, mild
      dyslipidemia, and hypertension, which are associated with subsequent development
      of type 2 diabetes mellitus and cardiovascular disease. Four groups of eight ZFR
      were gavaged daily with different supplements. For the initial three weeks, the
      control group of ZFR received only water, the second group received NBC 40 mcg
      elemental chromium/day, the third group received MSX 100 mg/day and the last
      group received HCA-SX 200 mg/day. During weeks 4-6, the doses of each treatment
      were doubled. The control animals lost approximately 50 g body weight (BW) per
      rat over 6 weeks of treatment, which is characteristic of these animals in
      declining health. In contrast, eight ZFR receiving NBC lost approximately 9 g BW
      per rat, while rats consuming MSX lost 16 g BW per rat. However, ZFR receiving
      HCA-SX simulated the pattern in the control group because these animals lost
      approximately 46 g BW per rat. The wide individual variations resulted in a lack
      of statistical significance among groups. Nevertheless, 75% of the ZFR in the
      control group lost more than 50 g BW over the 6 weeks duration, whereas none of
      the ZFR receiving NBC, 25% of the ZFR receiving MSX and 57% of the ZFR receiving
      HCA-SX lost over 50 g BW over the 6 weeks of the study. ZFR in all 3 treatment
      groups showed significantly lower blood pressures as compared to control, which
      seemed to be dose related. The general trend was for renal and liver blood
      parameters, hepatic and renal lipid peroxidation and DNA fragmentation to improve
      due to the supplementation of these natural products. Treatment of animals with a
      combination of these three novel supplements resulted in a lower SBP and
      maintenance of BW compared to control animals. These results demonstrate that
      elderly diabetics and even aging individuals might benefit from a similar
      regimen.

PMID- 14577613
TI  - Inducible expression of long-chain acyl-CoA hydrolase gene in cell cultures.
AB  - A long-chain acyl-CoA hydrolase, BACH, is markedly distributed in the brain and
      localized in neurons. However, the physiological significance of BACH is unclear.
      To study the gene function, we expressed the mouse BACH gene in C3H 10T1/2
      fibroblastic cells using a mifepristone (RU486)-inducible gene expression system.
      A cell clone, 10T-S6/44, was generated by stable transfection of two plasmids
      encoding a mifepristone-dependent transactivator and an inducible transgene
      product, BACH with a C-terminal MYC-tag (BACH-MYC). The transgene expression in
      the 10T-S6/44 cells was tightly regulated by mifepristone. Induction of BACH-MYC
      and an increase in palmitoyl-CoA hydrolase activity were observed in the cells
      treated with 3 x 10(-11) M mifepristone and reached maximal levels at a
      concentration of 1 x 10(-9) M for 48 h. The growth rate of cells showing the
      maximal induction of BACH-MYC was reduced, whereas phospholipid synthesis was
      unchanged. These results suggested that BACH affects specific cellular systems
      and functions, but not all acyl-CoA-utilizing processes.

PMID- 14577614
TI  - Effects of 2-amino-4,6-dinitrotoluene on p53 tumor suppressor gene expression.
AB  - 2-Amino-4,6-dinitrotoluene (2-Am-DNT) and its isomers are the most common
      metabolites of 2,4,6-trinitrotoluene (TNT). It is desirable to know the toxicity
      of this metabolite particularly because of its role in carcinogenicity and
      because it could contaminate drinking water. We used MCF-7 human breast cancer
      cells which have p53 tumor suppressor gene in wild type form in both the loci.
      Immunoblotting with p53 antibody showed enhanced p53 level in treated cells
      compared to untreated control cells. Similarly, p53 DNA-protein binding assays
      (gel-shift) showed accumulation of p53 protein in treated cells. This is the
      first report which shows p53 accumulation in 2-Am-DNT treated cells providing
      evidence of potential carcinogenic effects of 2-Am-DNT.

PMID- 14577615
TI  - Characterization of a pseudogene for murine methylenetetrahydrofolate reductase.
AB  - Methylenetetrahydrofolate reductase (MTHFR) reduces 5,10
      methylenetetrahydrofolate to 5-methyltetrahydrofolate, the major carbon donor in
      the remethylation of homocysteine to methionine. Mild MTHFR deficiency, due to a
      common variant at nucleotide 677, has been reported to influence risk for several
      disorders including cardiovascular disease, neural tube defects, pregnancy
      complications and cancer. In recent work, we characterized the complete cDNA and
      gene sequences in the human and mouse genes, which had previously been mapped to
      chromosomes 1 and 4, respectively. During the course of this work, we observed
      that PCR primers in exons 1 and 2 of Mthfr generated amplicons of the expected
      size for the normal Mthfr transcript, using both reverse-transcribed RNA and
      genomic DNA as templates. These findings alluded to the existence of a pseudogene
      in the murine genome. Here, we report the characterization of this pseudogene.
      The absence of intron 1, the partial retention of intron 2, the location of this
      gene on chromosome 5, and the presence of sequences unrelated to Mthfr at the 5'
      and 3' ends of the 1259 bp fragment are features that are indicative of a
      partially-processed pseudogene, that we have designated Mthfr-ps. A Mthfr-ps
      transcript was not detectable by sensitive RT-PCR using assays designed to
      simultaneously detect the authentic Mthfr transcript. The structure of this
      paralogous gene and the identification of a repeat sequence at the 3' end of this
      pseudogene suggest that it arose by retrotransposition of a mis-spliced Mthfr
      transcript. Investigations of the Mthfr gene should take into account the
      presence of the non-functional Mthfr-ps to avoid misinterpretation of results.

PMID- 14577616
TI  - Resistin expression in different adipose tissue depots during rat development.
AB  - Resistin is a hormonal factor synthesised by adipocytes that was first thought to
      be related with the resistance to insulin in obesity, but whose function is not
      yet completely established. Here we have studied the ontogenic pattern of
      resistin mRNA expression in different white adipose tissue depots (WAT)-
      epididymal, inguinal, mesenteric and retroperitoneal--and in brown adipose tissue
      (BAT), as well as the circulating resistin levels, in rats of different ages
      (from the suckling period to one year of age). Resistin mRNA was determined by
      Northern blotting, and serum levels by enzyme immunoassay. In WAT, resistin
      expression remains almost constant with age, except in early development, where
      there is a peak of expression in the epididymal and retroperitoneal depots, and a
      decrease in the inguinal one, while the expression remains constant for the
      mesenteric depot. Moreover, there is a site-specific difference regarding
      resistin expression: all the depots express characteristic levels of mRNA,
      especially at the age of 2 months, the moment when resistin mRNA levels are
      significantly higher in the epididymal and the retroperitoneal than in the
      inguinal and mesenteric WAT and than in the BAT. The transient increased resistin
      expression in the epididymal and the retroperitoneal WAT at a period of time in
      which there is a change in diet (from milk to chow) suggests a common nutritional
      regulation of the resistin gene. Circulating resistin levels increase with age
      probably reflecting the increase in the body fat content.

PMID- 14577617
TI  - Function of beta-carotene and tocopherol in photosystem II.
AB  - New and known structural and functional insights in the role of beta-carotene and
      of alpha-tocopherol in photosytem II are reviewed. A concept is presented
      connecting the failure of P680 triplet quenching by beta-carotene with the
      formation of singlet oxygen and its scavenging in the turnover of the D1 protein
      and by tocopherol in the maintenance of PS II structure and function.

PMID- 14577618
TI  - Rhoiptelenol and rhoiptelenone, two pentacyclic triterpenes from Sideritis
      macrostachya.
AB  - The pentacyclic triterpenes rhoiptelenol and rhoiptelenone have been isolated
      from Sideritis macrostachya. Rhoiptelenone is a new natural compound, whose
      structure has been determined as D:B-friedo-urs-5-en-3-one. The 1H and 13C NMR
      spectra of rhoiptelenol, rhoiptelenol acetate and glutinol have been reassigned.
      The natural occurrence of the D:B-friedo-ursene and D:B-friedo-oleanene
      derivatives has been examined.

PMID- 14577619
TI  - Tropane alkaloids from Latua pubiflora.
AB  - Four known tropane alkaloids were isolated from the leaves of the endemic Chilean
      plant Latua pubiflora (Solanaceae). For the first time; 3alpha
      cinnamoyloxitropane and apoatropine are reported in this plant. Scopolamine and
      hyoscyamine were previously reported.

PMID- 14577620
TI  - Chemical composition of the fixed and volatile oils of Nigella sativa L. from
      Iran.
AB  - The chemical composition of the extracted fixed oil (total fatty acid
      composition) and volatile oil of Nigella sativa L. seeds grown in Iran were
      determined by GC and GC/MS. Eight fatty acids (99.5%) and thirty-two compounds
      (86.7%) have been identified in the fixed and volatile oils, respectively. The
      main fatty acids of the fixed oil were linoleic acid (55.6%), oleic acid (23.4%),
      and palmitic acid (12.5%). The major compounds of the volatile oil were trans
      anethole (38.3%), p-cymene (14.8%), limonene (4.3%), and carvone (4.0%).

PMID- 14577621
TI  - Thalictricoside, a new phenolic compound from Thalictrum orientale.
AB  - From the underground parts of Thalictrum orientale Boiss., a new phenolic
      compound 1 was isolated in addition to one known cyanoglycoside, lithospermoside
      (2). For the structure elucidation of all compounds, 1D- and 2D-NMR techniques
      (DEPT, COSY, HMBC, HSQC) and MS (HR-MALDI) were used. The structure of the new
      compound was established as 2-(4'-hydroxyphenyl)-nitroethane-4'-O-[beta
      xylopyranosyl-(1 --> 6)-beta-glucopyranoside] (1).

PMID- 14577622
TI  - Pyrone glycosides from Acosmium panamense (Benth.) Yacovlev.
AB  - Besides caffeic acid three pyrones have been isolated from aquous bark extracts
      from Acosmium panamense and their structures were determined using
      spectroscopical methods. Besides the already described desmethylyangonine its O4'
      mono as well as the di(1-6)glucoside are found the first time.

PMID- 14577623
TI  - The first occurrence in nature of two compounds from hops.
AB  - Two compounds, (p-methoxyphenyl) diphenylmethanol (1) and tribenzylamine (2),
      were isolated from Humulus lupulus. Their structures were established on the
      basis of spectral evidence (MS, IR, NMR, HMBC, HMQC, 1H-1H COSY experiments).
      Compounds 1 and 2 were found as natural products at the first time.

PMID- 14577624
TI  - Floral resin of Tovomitopsis saldanhae (Guttiferae) and 7-epi-nemorosone:
      structural revision.
AB  - The floral resin of Tovomitopsis saldanhae (Guttiferae) is composed of
      poliisoprenylated benzophenone and the major constituent is 7-epi-nemorosone
      which has now been revised.

PMID- 14577625
TI  - Two new 24-isopropenyl-lanostanoids from Tillandsia brachycaulos.
AB  - The leaves of Tillandsia brachycaulos afforded two novel tetracyclic
      triterpenoids identified as (24S)-24-isopropenyl-29-nor-5alpha-lanosta-7-en-3beta
      ol (1) and (24S)-24-isopropenyl-29-nor-5alpha-lanosta-7-en-3-one (2), in addition
      to the known isopimaric acid (3) and chlorogenic acid (4). Their structures were
      elucidated on the basis of spectral analysis, including homo- and heteronuclear
      correlation NMR experiments (COSY, ROESY, HMQC and HMBC) and by comparison with
      data in the literature. The antimicrobial and antifungal activities were studied.
      The compounds did not show significant activity.

PMID- 14577626
TI  - A new polyisoprenylated phloroglucinol derivative from Hypericum perfoliatum
      (Clusiaceae).
AB  - Hyperfoliatin, a new polyisoprenylated phloroglucinol derivative was isolated
      from the aerial parts of Hypericum perfoliatum (Clusiaceae) collected in Algeria.
      The structure of hyperfoliatin was elucidated on the basis of its spectral data,
      mainly MS and multiple-pulse NMR.

PMID- 14577627
TI  - Chemical constituents of the basidiomycete Cortinarius umidicola.
AB  - A new natural pyridine derivative (3-aldehyde-2-amino-6-methoxypyridine, 1)
      together with (R)-glycidyl octadecanoate (2) and five ergostane-type sterols (3
      7) were isolated from the fruiting bodies of the basidiomycete Cortinarius
      umidicola Kauffm. Their structures were established by spectral methods (MS, IR,
      1D and 2D-NMR experiments).

PMID- 14577628
TI  - Further meroterpenes produced by Penicillium sp., an endophyte obtained from
      Melia azedarach.
AB  - From the methanol extract of Penicillium sp. cultivated on sterilized rice for
      three weeks we isolated three new meroterpenes preaustinoid A1, A2 and B1. The
      fungus was isolated from the root bark of Melia azedarach after surface
      sterilization. The structures of these compounds were identified by intensive
      spectroscopic studies.

PMID- 14577629
TI  - Antibacterial polyphenol from Erodium glaucophyllum.
AB  - Geraniin and gallic acid were isolated from the alcohol extract of the aerial
      parts of Erodium glaucophyllum (Geraniaceae). The identity of the compounds was
      verified through different physical and spectrometric methods. The antibacterial
      and antifungal activity of geraniin is presented.

PMID- 14577630
TI  - Antiproliferative effects of several compounds isolated from Amburana cearensis
      A. C. Smith.
AB  - Amburana cearensis a common tree found in Northeastern Brazil is widely used in
      folk medicine. The present work evaluated the cytotoxicity of kaempferol,
      isokaempferide, amburoside A and protocatechuic acid isolated from the ethanol
      extract of the trunk bark of A. cearensis. The compounds were tested for their
      cytotoxicity on the sea urchin egg development, hemolysis assay and 3-(4,5
      dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay using tumor cell
      lines. Isokaempferide and kaempferol, but not amburoside A and protocatechuic
      acid, inhibited the sea urchin egg development as well as tumor cell lines, but
      in this assay isokaempferide was more potent than kaempferol. Protocatechuic acid
      was the only compound able to induce hemolysis of mouse erythrocytes, suggesting
      that the cytotoxicity of kaempferol and isokaempeferide was not related to
      membrane damage.

PMID- 14577631
TI  - Chemical composition and biological activity of Nepeta parnassica oils and
      isolated nepetalactones.
AB  - Essential oils of Nepeta parnassica, collected at different developmental stages,
      were analyzed by means of GC/MS. From the fifty-five identified constituents in
      samples A and B, representing 94.8% and 98.7% of the oils respectively,
      4a(alpha),7alpha,7alpha(beta)-nepetalactone (22.0%), 1,8-cineole (21.1%), alpha
      pinene (9.5%) and 4a(alpha),7,beta,7alpha(beta)-nepetalactone (7.9%) were the
      major components of sample A (vegetative stage), whereas in sample B (flowering
      stage) the main contributors were 1,8-cineole (34.6%), 4a(alpha),7alpha,7a(alpha)
      nepetalactone (17.3%), alpha-pinene (11.4%) and 4a(alpha),7alpha,7alpha(beta)
      nepetalactone (8.9%). The oils were tested on human health important insects such
      as the Pogonomyrmex sp. ants and the Culex pipiens molestus mosquitoes with
      promising results on insect repellency/toxicity.

PMID- 14577632
TI  - Analysis of essential oil of Coridothymus capitatus (L.) and its antibacterial
      and antifungal activity.
AB  - The water-distilled essential oil the leaves of Coridothymus capitatus were
      analyzed by GC/MS and also analyzed by direct thermal desorption GC/MS.
      Comparison was made between two analyses techniques. The essential oil consisted
      mainly of monoterpenes 98.9%, while oxygenated hydrocarbons were identified as
      55.6 % and non-oxygenated hydrocarbons as 43.6%. As major components were found
      carvacrol (35.6%), p-cymene (21.0%), thymol (18.6%), gamma-terpinene (12.3%),
      alpha-terpinene (3.2%), beta-myrcene (3.0%) and alpha-thujene (1.3%) by
      hydrodistillation and by the GC/MS method. The direct thermal desorption GC/MS
      analysis also showed the same major components, namely carvacrol (51.6%), thymol
      (21.7%), p-cymene (9.7%) gamma-terpinene (8.2%), alpha-terpinene (1.64%). The
      essential oil of C. capitatus showed strong activity against S. aureus, P.
      vulgaris, P. aeruginosa, E. coli, K. pneumonia, B.

PMID- 14577633
TI  - Synthesis of montroumarin.
AB  - A simple stereoselective synthesis of montroumarin [(3S)-6,8-dihydroxy-3-phenyl
      3,4-dihydroisocoumarin] isolated from Montrouziera sphaeroidea has been achieved.
      Condensation of benzoyl chloride with 3,5-dimethoxyhomophthalic acid afforded 6,8
      dimethoxy-3-phenylisocoumarin (3) which on sequential saponification and
      esterification yielded the keto ester 5. Enantioselective reduction of the latter
      with baker's yeast directly furnished the (3S)-6,8-dimethoxy-3-phenyl-3,4
      dihydroisocoumarin (6) in good enantioselectivity which on demethylation provided
      montroumarin. All of the synthesized compounds were examined in vitro for
      antifungal activity.

PMID- 14577634
TI  - GC/MS analysis of some bioactive constituents from Carthamus lanatus L.
AB  - Sterols, triterpenes, volatiles, polar and other constituents in aerial parts of
      Carthamus lanatus were analyzed by gas chromatography-mass spectrometry. Over 90
      compounds were identified most of them new for the species. Sitosterol and
      stigmasterol were the most abundant of 10 sterols identified in the sterol
      fraction. Taraxasterol, alpha- and beta-amyrine prevailed in the triterpene
      fraction. Volatiles, sterols and a fraction of the dichloromethane extract showed
      strong cytotoxicity (Artemia salina assay).

PMID- 14577635
TI  - Bioactive phenolics from Carthamus lanatus L.
AB  - Two flavonoid aglycons, eight flavonoid glycosides, chlorogenic acid and syringin
      were isolated from aerial parts of Carthamus lanatus. Isorhamnetin 3-O-beta-D
      glucoside and chlorogenic acid were found for the first time in the genus
      Carthamus and respectively, quercimeritrin, astragalin, kaempferol 3-O-beta-D
      sophoroside and syringin in the species. The ethyl acetate fraction of the
      methanol extract exhibited a higher antioxidant activity than the butanol
      fraction measured by the alpha,alpha-diphenyl-beta-picrazylhydrazyl (DPPH) free
      radical scavenging assay. Cytotoxicity and antioxidant activities of the main
      constituent, luteolin 7-O-beta-D-glucoside, were evaluated.

PMID- 14577636
TI  - Influence of carbon, nitrogen and phosphorous sources on glucoamylase production
      by Aspergillus awamori in solid state fermentation.
AB  - It was the objective of the present study to increase the production of
      glucoamylase by Aspergillus awamori through solid state fermentation, using wheat
      bran as the main carbon source and (NH4)2SO4, urea, KH2PO4, glucose, maltose and
      starch as additional nitrogen, phosphorus, and carbon sources. The production of
      glucoamylase is strongly influenced by N and C sources. A 100% increase was
      observed when the (NH4)2SO4 was replaced by urea, with C/N = 4.8, using maltose
      as the additional carbon source. C/P ratios in a range of 5.1 to 28.7 did not
      induce glucoamylase production under the studied conditions.

PMID- 14577637
TI  - Tyrosinase inhibition kinetics of anisic acid.
AB  - Anisic acid (p-methoxybenzoic acid) was characterized as a tyrosinase inhibitor
      from ani-seed, a common food spice. It inhibited the oxidation of L-3,4
      dihydroxyphenylalanine (L-DOPA) catalyzed by tyrosinase with an IC50 of 0.60 mM.
      The inhibition of tyrosinase by anisic acid is a reversible reaction with
      residual enzyme activity. This phenolic acid was found to be a classical
      noncompetitive inhibitor and the inhibition constant K(I) was obtained as 0.603
      mM. Anisic acid also inhibited the hydroxylation of L-tyrosine catalyzed by
      tyrosinase. The lag phase caused by the monophenolase activity was lengthened and
      the steady-state activity of the enzyme was decreased by anisic acid.

PMID- 14577638
TI  - Tyrosinase inhibitors from galls of Rhus javanica leaves and their effects on
      insects.
AB  - As a defense mechanism of the leaves of Rhus javanica (Anacardiaceae) against the
      aphid Melaphis chinensis (Aphididae) attack, tannic acid is rapidly accumulated
      and forms galls along the midrib of the leaves resulting in a unique natural
      medicine Gallae Rhois. Tannic acid was found to inhibit the oxidation of L-3,4
      dihydroxyphenylalanine (L-DOPA) catalyzed by tyrosinase (EC 1.14.18.1) with an
      IC50 of 22 microM. The aphid would detoxify the ingested toxic tannic acid to
      relatively nontoxic gallic acid, whereas the non-adapted pink bollworm
      Pectinophora gossypiella larvae are sensitive to the ingested tannic acid.

PMID- 14577639
TI  - Biodegradation of naphthalene by free and alginate entrapped Pseudomonas sp.
AB  - Naphthalene degradation by freely suspended and immobilized cells of Pseudomonas
      sp. isolated from contaminated effluents has been investigated in batch cultures
      and continuously in a packed bed reactor. Naphthalene concentration was varied
      from 25 mM to 75 mM, the temperature (30 degrees C) and pH (7.0) were kept
      constant. The results showed good acclimation of the strain to carbon source and
      degradation rate was highly affected by initial concentration. Alginate-entrapped
      cells have given good yields although initial rates were not as high as those
      encountered with free cells. A first order exponential decay kinetic model was
      proposed with values of parameters for each initial concentration. A laboratory
      scale packed-bed bioreactor was designed using parameters calculated above and
      continuous experiments were realized at different flow rates (100 to 200 ml/h),
      with different feed concentrations and operating during 30 days. The conversion
      at low feed concentrations and low flow rates was complete whereas at high flow
      rates and high concentrations it was less efficient because of diffusional
      limitations and short residence time.

PMID- 14577640
TI  - DNA breaks induction by mimosine.
AB  - Mouse erythroleukemic F4 N cells were treated with mimosine, etoposide, Fe(II)
      EDTA, and Cu(II) in the presence of ascorbate. DNA was isolated and subjected to
      agarose gel electrophoresis and the size and distribution of the DNA fragments
      produced by the agents were compared. With increasing concentration of Cu(II) the
      production of DNA fragments was increased without decrease of the average length
      of the fragments, and their sizes were similar to those produced by etoposide as
      expected for cleavage of DNA at the nuclear matrix attachments sites. In
      contrast, mimosine and Fe(II) produced fragments of random size and with the
      progression of the reaction the average length of the fragments decreased. These
      results indicate that mimosine cuts DNA in a random fashion, regardless of its
      higher order chromatin organization. A conclusion is drawn that the DNA fragments
      obtained after mimosine treatment are a result of mimosine-assisted, Fe(II)
      dependent Fenton-like reactions randomly cutting chromosomal DNA.

PMID- 14577641
TI  - Expression of the endoplasmic reticulum chaperone GRP94 gene in ischemic gerbil
      brain.
AB  - GRP94 (glucose regulated protein 94) gene expression in the ischemic-hippocampus
      of gerbils, which was induced by a temporary occlusion of the bilateral common
      carotid arteries (CCAs), was tested by Northern blot analysis. The maximum GRP94
      gene expression level was detected at the occipital lobe 10 min after the
      induction of ischemia. In the hippocampus, GRP94 gene expression reached a
      maximum 15 min after inducing ischemia. Following reperfusion, the maximum
      expression level was shown at 12 h and continuing thereafter.

PMID- 14577642
TI  - A novel cyclopeptide from a bacterium associated with the marine sponge Ircinia
      muscarum.
AB  - A new cyclotetrapeptide 1, together with three known cyclopeptides were isolated
      from the exo-cellular extract of Pseudomonas sp. a bacterium associated with the
      sponge Ircinia muscarum. The structure of 1 was suggested on the basis of
      spectroscopic analytical data and chemical degradation.

PMID- 14577644
TI  - Elucidation of endemic neurodegenerative diseases--a commentary.
AB  - Recent investigations of scrapie, Creutzfeldt-Jakob disease (CJD), and chronic
      wasting disease (CWD) clusters in Iceland, Slovakia and Colorado, respectively,
      have indicated that the soil in these regions is low in copper and higher in
      manganese, and it has been well-known that patients of ALS or Parkinson's disease
      were collectively found in the New Guinea and Papua islands, where the
      subterranean water (drinking water) contains much Al3+ and Mn2+ ions. Above facts
      suggest that these neurodegenerative diseases are closely related with the
      function of a metal ion. We have investigated the chemical functions of the metal
      ions in detail and established the unique mechanism of the oxygen activation by
      the transition metal ions such as iron and copper, and pointed out the notable
      difference in the mechanism among iron, aluminum and manganese ions. Based on
      these results, it has become apparent that the incorporation of Al(III) or Mn(II)
      in the cells induces the "iron-overload syndrome", which is mainly due to the
      difference in an oxygen activation mechanism between the iron ion and Al(III) or
      the Mn(II) ion. This syndrome highly promotes formation of hydrogen peroxide, and
      hydrogen peroxide thus produced can be a main factor to cause serious damages to
      DNA and proteins (oxidative stress), yielding a copper(II)- or manganese(II)
      peptide complex and its peroxide adduct, which are the serious agents to induce
      the structural changes from the normal prion protein (PrP(c)) to abnormal disease
      causing isoforms, PrP(Sc), or the formation of PrP 27-30 (abnormal cleavage at
      site 90 of the prion protein). It seems reasonable to consider that the essential
      origin for the transmissible spongiform encephalopathies (TSEs) should be the
      incorporation and accumulation of Al(III) and Mn(II) ions in the cells, and the
      sudden and explosive increase of scrapie and bovine spongiform encephalopathy
      (BSE) in the last decade may be partially due to "acid rain", because the acid
      rain makes Al(III) and Mn(II) ions soluble in the subterranean aquifers.

PMID- 14577643
TI  - Antimicrobial compounds of fungi vectored by Clusia spp. (Clusiaceae) pollinating
      bees.
AB  - The production of antimicrobial compounds by fungi associated with Clusia spp.
      pollinating bees (Trigona sp., Trigonini) was investigated in order to approach
      natural mechanisms of microbial density control within nest environment. By using
      a bioassay-guided approach based on bioautography and minimal inhibitory
      concentration (MIC), known alpha,beta-dehydrocurvularin and curvularin were
      isolated from Curvularia eragrostidis (CCT 5634) and Curvularia pallescens (CCT
      5654), and known cochlioquinone A and isocochlioquinone A were isolated from
      Drechslera dematioidea (CCT 5631).

PMID- 14577645
TI  - A new sweet dihydrochalcone-glucoside from leaves of Lithocarpus pachyphyllus
      (Kurz) Rehd. (Fagaceae).
AB  - A new sweet dihydrochalcone-glucoside, trilobatin 2"-acetate (1), was isolated
      from the leaves of Lithocarpus pachyphyllus, together with phlorizin and
      trilobatin. The structures were established by spectroscopic methods, including
      one- and two-dimensional NMR (COSY, HMQC and HMBC).

PMID- 14577646
TI  - Quantitative analysis of flavonoids in the flowers and leaves of Ficaria verna
      Huds.
AB  - The quantitative determination of flavonoid compounds in flowers and leaves of
      Ficaria verna Huds. (Ranunculaceae) was carried out in different growing seasons
      of the plant, using Christ-Muller's method (Polish Pharmacopoeia, 1999) and high
      performance liquid chromatography (HPLC) analysis after acid hydrolysis. The
      flavonoid content was much higher in flowers than in leaves.

PMID- 14577647
TI  - Transcription factor as molecular targets: is transcription factor decoy a novel
      drug?

PMID- 14577648
TI  - New vector innovation for drug delivery: development of fusigenic non-viral
      particles.
AB  - Efficient and minimally invasive drug delivery systems have been developed to
      treat intractable human diseases. One approach has been the development of
      chimeric vector systems combining at least two different vector systems. Based on
      this concept, chimeric drug delivery systems that combine viral and non-viral
      features have been developed. Fusigenic non-viral particles have been constructed
      by conferring viral fusion proteins onto non-viral vectors. HVJ (hemagglutinating
      virus of Japan; Sendai virus)-liposomes were constructed by the combination of
      DNA-loaded liposomes with a fusigenic envelope derived from HVJ (hemagglutinating
      virus of Japan, Sendai virus). Reconstituted HVJ-liposomes were also developed by
      the insertion of isolated fusion proteins of HVJ into DNA-loaded liposomes.
      Recently, the technology has been developed to incorporate macromolecules
      directly into inactivated HVJ particles without liposomes. The resulting HVJ
      envelope vector introduced plasmid DNA, efficiently and rapidly into both
      cultured cells in vitro and organs in vivo. Furthermore, proteins, synthetic
      oligonucleotides and drugs have also been effectively introduced into cells using
      the HVJ envelope vector. The HVJ envelope vector will be a promising tool for
      both ex vivo and in vivo gene therapy experiments.

PMID- 14577649
TI  - Transcription factors as molecular targets: molecular mechanisms of decoy ODN and
      their design.
AB  - Recent progress in cellular and molecular research has provided a new technique
      to inhibit target gene expression based on DNA technology such as antisense
      oligonucleotides (ODN) or decoy ODN. Especially, application of an antisense
      strategy to regulate the transcription of disease-related genes in vivo has
      important therapeutic potential to treat or cure a variety of diseases and
      abnormal physiological conditions. On the other hand, recently, a successful ODN
      based approach termed decoy ODN has used synthetic ODN containing an enhancer
      element that can penetrate cells, to bind to sequence-specific DNA-binding
      proteins and interfere with transcription in vitro and in vivo. Transfection of
      cis-element double-stranded decoy ODN has been reported as a new powerful tool in
      a new class of anti-gene strategies to treat various diseases as gene therapy or
      as a research tool to examine the molecular mechanisms of expression of a
      specific gene. Transfection of double-stranded ODN corresponding to the cis
      sequence will result in attenuation of the authentic cis-trans interaction,
      leading to removal of trans-factors from the endogenous cis-elements with
      subsequent modulation of gene expression. To date, we have chosen several target
      transcription factors such as NFkappaB (nuclear factor-kappaB) and E2F to prevent
      the progression of diseases, and negative regulatory element (NRE) for the renin
      gene and angiotensinogen gene-activating element (AGE) for the angiotensinogen
      gene to examine the molecular mechanisms of gene expression. In this section, we
      introduce the principles of the decoy strategy and how to design decoy ODN.

PMID- 14577650
TI  - Gene therapy for arthritis.
AB  - Recent progress in molecular biology has provided application of gene transfer
      methods in arthritis. Two clinical trails using ex vivo retrovirus mediated
      delivery of interleukin -1 receptor antagonist gene for rheumatoid arthritis has
      begun in USA and Germany. However, there are still many issues to be elucidated;
      one is the development of gene delivery system, and the other is the selection of
      therapeutic gene. Arthritis is nonlethal disease, and safety is one of the
      important issues. Currently viral mediated vectors are major even in clinical
      trials however, non viral efficient gene transfer system should be developed in
      future. Recently the application of DNA technologies, such as antisense
      oligonucleotide (ODN) strategies to regulate the transcription of disease-related
      genes in vivo, has significant therapeutic potential. Transfection of cis-clement
      double-stranded oligonucleotides (decoy ODN) for nuclear factor kappaB binding
      site has been reported as a new powerful tool in arthritis. The concept of
      regulation the disease related gene expression at the level of transcriptional
      factor may be more therapeutic effects compared with monotherapy in arthritis.

PMID- 14577651
TI  - Oligonucleotide-based molecular therapy for restenosis after angioplasty.
AB  - Molecular therapy is emerging as a potential strategy for the treatment of
      cardiovascular disease such as restenosis after angioplasty, vascular bypass
      graft occlusion, transplant coronary vasculopathy, homozygous familial
      hypercholesterolemia and cystic fibrosis, for which no known effective therapy
      exists. Molecular biology and pathophysiology of the cardiovascular system have
      started to emerge, and the time is ripe for the introduction of gene therapy to
      the management of cardiovascular disorders. In this review, we have focused on
      the future potential of oligonucleotide-based gene therapy for restenosis after
      angioplasty, which still remains an issue in the field of cardiovascular disease.

PMID- 14577652
TI  - Advantages of the circular dumbbell decoy in gene therapy and studies of gene
      regulation.
AB  - Decoy oligodeoxynucleotides (ODN) that can reduce the trans-activity of
      transcription factors may be highly useful in gene therapy and the study of
      transcriptional regulation. Several different types of these double-stranded DNA
      decoys have been developed, including unmodified oligonucleotide duplexes,
      alphabeta-anomeric oligonucleotides, and oligonucleotide duplexes with
      methylphosphonate- and phosphorothioate-modified linkages. The latter ODNs have
      been particularly extensively studied but suffer from a number of limitations,
      including their insensitivity to polymerases, their lack of sequence specificity,
      and their tendency to activate immune responses. To resolve these problems,
      circular dumbbell (CD) double-stranded ODNs were developed. These CD ODNs are
      constructed by the circularization of the 3' and 5' ends of the oligonucleotides
      and enzymatic ligation. They exhibit high resistance to nucleases, are easily
      taken up by cells, and have a nontoxic unmodified backbone that resembles natural
      DNA. In this article, we review the method of constructing CD ODNs and their
      advantages compared to other modified ODNs for use as transcription decoys.

PMID- 14577653
TI  - Aldose reductase: a novel target for cardioprotective interventions.
AB  - Recanalization therapy remains the most effective way for treatment of evolving
      myocardial infarction and thereby salvaging jeopardized tissue. However, the
      efficacy of reperfusion in limiting infarction and improving recovery of
      contractile function depends on the amount of irreversible damage occurring prior
      to initiating reperfusion and is related to failure of energy production to meet
      the basal needs of the injured myocardium. In recent years, a variety of
      metabolic therapies that enhance myocardial metabolism and attenuate changes in
      sodium and calcium homeostasis during ischemia have been proposed. They focus on
      (a) increasing myocardial glucose metabolism during ischemia or (b) inhibiting
      fatty acid metabolism to increase glucose use, and (c) inhibiting sodium and
      calcium influx pathways that deplete high energy phosphates. Recent studies from
      our laboratory showed that inhibition of aldose reductase, a key regulatory
      enzyme in the substrate flux via polyol pathway, reduces ischemic injury and
      improves functional and metabolic recovery after ischemia-reperfusion in hearts.
      These and subsequent studies have generated considerable interest in the use of
      aldose reductase inhibitors as potential therapeutic adjuncts in treating
      evolving myocardial infarction in patients. This review will discuss the
      mechanisms by which aldose reductase inhibitors protect ischemic myocardium and
      provide rationale for their use as cardioprotective drugs.

PMID- 14577654
TI  - Peptides and liposomes: from biophysical to immunogenic studies.
AB  - Synthetic peptide sequences constitute a useful tool to understand protein
      related diseases. A preliminary study consists of the analysis of peptide
      interaction with model membranes. The simplest one is based on monomolecular
      films of lipids spread at the air-water interface that imitate the interfacial
      environment in which some proteins function. Monolayer methodology provides a
      reliable screen of the extent to which hydrophobic interactions, charges, dipole
      potentials and subphase composition drive protein-lipid interaction. One step
      forward is based on the use of liposomes (lipid-based vesicles) that were
      originally introduced in 1965 as models of lipid bilayer membranes. Later, they
      have been widely studied as drug delivery systems mainly due to their safety,
      structural versatility, composition, fluidity and also because of their ability
      to incorporate almost any molecule regardless of its structure. In this sense,
      liposomes have been used as carriers of proteins and peptide antigens. Antigenic
      materials can be attached to the outer surface, encapsulated within the internal
      aqueous spaces or reconstituted within the lipid bilayers of the liposomes. In
      the present review we describe the steps going from the selection of peptides
      related to viral hepatitis proteins to its diagnostic and therapeutic
      application, with special emphasis on the use of model membranes to predict
      peptide mode of interaction with the target cell.

PMID- 14577655
TI  - Bacterial resistance to antimicrobial host defenses--an emerging target for novel
      antiinfective strategies?
AB  - Increasing bacterial resistance to virtually all available antibiotics causes an
      urgent need for new antimicrobial drugs, drug targets and therapeutic concepts.
      This review focuses on strategies to render bacteria highly susceptible to the
      antimicrobial arsenal of the immune system by targeting bacterial immune escape
      mechanisms that are conserved in a major number of pathogens. Virtually all
      innate molecules that inactivate bacteria, ranging from antimicrobial peptides
      such as defensins and cathelicidins to bacteriolytic enzymes such as lysozyme and
      group IIA phospholipase A2, are highly cationic in order to facilitate binding to
      the anionic bacterial cell envelopes. Bacteria have found ways to modulate their
      anionic cell wall polymers such as peptidoglycan, lipopolysaccharide, teichoic
      acid or phospholipids by introducing positively charged groups. Two of these
      mechanisms involving the transfer of D-alanine into teichoic acids and of L
      lysine into phospholipids, respectively, have been identified and characterized
      in Staphylococcus aureus, a major human pathogen in community- and hospital
      acquired infections. Inactivation of the responsible genes, dltABCD for
      alanylation of teichoic acids and mprF for lysinylation of phosphatidylglycerol,
      renders S. aureus highly susceptible to many human antimicrobial molecules and
      leads to profoundly attenuated virulence in several animal models. dltABCD- and
      mprF-related genes are found in the genomes of many bacterial pathogens
      indicating that the escape from human host defenses by modulation of the cell
      envelope is a general trait in pathogenic bacteria. This review suggests that
      inhibitors of DltABCD or MprF should have great potential in complementing or
      replacing the conventional antibiotic therapies.

PMID- 14577656
TI  - Antioxidants in peripheral arterial disease.
AB  - Peripheral arterial disease (PAD) is an important manifestation of systemic
      atherosclerosis that is characterized by obstruction of the arteries in the lower
      limbs. Experimental and epidemiological studies suggested a key role for
      oxidative stress in initiation and progression of the atherosclerotic process.
      The results of these studies provided a good basis for interventional trials with
      antioxidants, particularly with vitamin E, but the findings were conflicting. In
      this paper we review the observational and interventional studies with
      antioxidants, and ask whether vitamins supplementation should or should be not be
      recommended for PAD patients.

PMID- 14577657
TI  - Proteasomes as drug targets.
AB  - The ubiquitin-proteasome pathway plays a role in the degradation of the bulk of
      proteins in the cytoplasmic and nuclear compartments. In this pathway proteins
      are targeted for degradation by covalent ligation with ubiquitin, a reaction that
      requires ATP. Following the binding of the first ubiquitin molecule with the
      epsilon-amino group of a lysine residue of the substrate protein, a polyubiquitin
      chain is usually formed, in which the C-terminus of each ubiquitin unit is linked
      to a specific Lys residue of the previous ubiquitin. Central to this pathway is
      the 26S proteasome, a high molecular mass multifunctional protease which requires
      ATP for its catalytic activity. Substrates of the 26S proteasome are not only old
      or damaged proteins, but also short lived proteins functioning as regulatory
      factors in a large array of cellular processes, such as cell cycle progression,
      cell growth and gene expression, inflammatory response and immune surveillance. A
      number of inhibitors of the catalytic activity of proteasomes have been developed
      and successfully employed in the study of their functional and structural
      properties, as well as of their involvement in different cellular processes. Some
      of these molecules due to their toxicity are used only as experimental research
      tools; others instead are now in clinical trials for treatment of a variety of
      hematologic malignancies and solid tumors and of reperfusion injury occurring
      after cerebral ischemia and myocardial infarction. Furthermore, proteasome
      inhibitors are described to interfere with HIV maturation, budding and
      aggressiveness, and cytostatic drugs, as well as antiretroviral agents used in
      HAART, have been shown to behave in vitro and in cultured cell lines as
      inhibitors of proteasome proteolytic activity at therapeutic dosages.

PMID- 14577658
TI  - Supplementation with CLA: isomer incorporation into serum lipids and effect on
      body fat of women.
AB  - Animal studies have suggested that CLA, a natural component of meat and dairy
      products, may confer beneficial effects on health. However, human studies using
      supplementation with CLA have produced contradictory results. The aim of the
      present study was to further investigate the effect of CLA supplementation on
      human body fat, serum leptin, and serum lipids, as well as the incorporation of
      CLA isomers into serum lipids classes. Sixteen young healthy nonobese sedentary
      women received 2.1 g of CLA (divided equally between the cis,trans-9,11 and
      trans,cis-10,12 isomers) daily for 45 d and placebo for 45 d in a randomized
      double-blind crossover design. Body fat was estimated (by measurement of skinfold
      thickness at 10 sites), and blood was sampled at the beginning, middle, and end
      of the entire intervention period; an additional blood sample was obtained 2 wk
      thereafter. No significant differences in energy, carbohydrate, lipid, or protein
      intake existed between the CLA and placebo intake periods. No significant
      differences were found in body fat or serum leptin, TAG, total cholesterol, HDL
      cholesterol, and alanine aminotransferase between CLA and placebo. The CLA isomer
      content of serum TAG, phospholipids, and total lipids increased 2-5 times with
      CLA supplementation (P < 0.05). In contrast, the CLA content of cholesteryl
      esters did not change significantly. The period of 2 wk after the end of CLA
      supplementation was sufficient for its washout from serum lipids. These data
      indicate that supplementation with 2.1 g of CLA daily for 45 d increased its
      levels in blood but had no effect on body composition or the lipidemic profile of
      nonobese women.

PMID- 14577659
TI  - Vitamin E supplementation increases circulating vitamin E metabolites tenfold in
      end-stage renal disease patients.
AB  - Vitamin E supplementation could elevate circulating vitamin E metabolites while
      modulating oxidative and inflammatory status in end-stage renal failure patients
      undergoing hemodialysis. Plasma concentrations of carboxyethyl-hydroxychromanols
      (alpha- and gamma-CEHC), ascorbic acid, alpha- and gamma-tocopherols, F2
      isoprostanes, and inflammatory biomarkers [tumor necrosis factor-alpha (TNF
      alpha), interleukin-6 (IL-6), ferritin, and C-reactive protein (CRP)] were
      measured in blood samples obtained from patients (n = 11) before and after
      dialysis on two occasions prior to, and at 1 and 2 mon of daily vitamin E
      supplementation (400 IU RRR-alpha-tocopherol). Supplementation nearly doubled
      plasma alpha-tocopherol concentrations (from 18 +/- 0.5 to 31 +/- 1.7 microM, P <
      0.0001), whereas gamma-tocopherol concentrations decreased (from 2.8 +/- 0.3 to
      1.7 +/- 0.2 microM, P = 0.001). Serum alpha-CEHC increased 10-fold from 68 +/- 3
      to 771 +/- 175 nM (P < 0.0001), and gamma-CEHC increased from 837 +/- 164 to 1136
      +/- 230 nM (P = 0.008). Vitamin E supplementation also increased postdialysis
      hematocrits from 38 +/- 1% to 41 +/- 1% (P < 0.001). Dietary antioxidant intakes
      (vitamins E and C) were low in most subjects; plasma ascorbic acid levels (88 +/-
      27 microM) decreased significantly with dialysis (33 +/- 11 microM, P = 0.01).
      Plasma IL-6, CRP, TNF-alpha, and free F2-isoprostane concentrations were elevated
      throughout the study. There is a complex relationship between chronic
      inflammation and oxidative stress that is not mitigated by short-term vitamin E
      supplementation. Importantly, serum vitamin E metabolite concentrations that
      increased 10-fold within 30 d of supplementation did not increase further,
      suggesting routes other than urine for removal of metabolites.

PMID- 14577661
TI  - Hepatic delta9, delta6, and delta5 desaturations in non-insulin-dependent
      diabetes mellitus eSS rats.
AB  - Both diabetes mellitus type 1 and diabetes mellitus type 2 are widespread
      diseases that alter carbohydrate and lipid metabolism. e Stilmann-Salgado (eSS)
      rats are experimental animals that spontaneously evolve to a state similar to
      that of young people affected by non-insulin-dependent diabetes mellitus (NIDDM;
      type 2). Using 6-mon-old eSS rats that, according to the literature [Martinez,
      S.M., Tarres, M.C., Montenegro, S., Milo, R., Picena, J.C., Figueroa, N., and
      Rabasa, S.R. (1988) Spontaneous Diabetes in eSS Rats, Acta Diabetol. Lat. 25, 303
      313], had already developed insulin resistance, we investigated the changes
      evoked on delta9, delta6, and delta5 liver desaturases. The abundance of mRNA and
      enzymatic activities were measured, as well as the FA composition of liver
      microsomal lipids. Compared to control rats, the mRNA content and activity of SCD
      1 (stearoyl CoA-desaturase, isoform of the delta9 desaturase) were significantly
      higher, whereas the mRNA and activities of delta6 and delta5 desaturases were not
      significantly modified. Correspondingly, the proportion of 18:1n-9 and the ratios
      of 18:1n-9/18:0 and 16:1/16:0 in lipids were significantly increased, whereas the
      proportion of 20:4n-6 was unaltered. These effects were found while glycemia was
      constant or increased. The results are completely opposite those described in
      insulin-dependent diabetes mellitus (type 1), in which a depression of all the
      desaturases is found. They suggest that in eSS rats, the activities of the
      desaturases were not modified by an insulin-resistance effect. Moreover, we
      suggest that the enhancement of SCD-1 activity might be considered as another
      typical sign of the NIDDM syndrome, because it has also been found in other
      animal models of NIDDM, for example, the ones evoked by the sucrose-rich diet and
      in the Zucker rat.

PMID- 14577660
TI  - A sardine oil-rich diet increases iron absorption but does not compensate the
      hypoferremia associated with inflammation.
AB  - Inflammatory disorders are associated with a decrease in iron absorption because
      of the blockade of iron in storage organs. Fish oils, rich in n-3 PUFA, are used
      to prevent and treat inflammatory disorders and increase iron absorption in
      noninflamed rats. Here we examine whether n-3 PUFA prevent inflammation-related
      hypoferremia. Two groups of rats were fed isoenergetic semipurified diets (a
      standard diet and a sardine oil-rich diet). A carrageenan granuloma was induced
      in half of the rats of each dietary group. Ferrokinetic studies using 59Fe,
      hematological analyses, and iron store evaluation were performed in noninflamed
      and inflamed rats. Although dietary n-3 PUFA increased 59Fe absorption in
      carageenan-treated rats, they did not restore the hypoferremia associated with
      inflammation, which is due to several mechanisms. Among these mechanisms, the
      blockade of iron in storage organs is relevant. However, this blockade was less
      evident in the spleen of inflamed rats fed the sardine oil diet.

PMID- 14577662
TI  - Influence of temperature and high dietary linoleic acid content on
      esterification, elongation, and desaturation of PUFA in Atlantic salmon
      hepatocytes.
AB  - The esterification, desaturation, and elongation of [1-14C]18:3n-3, [1-14C]18:2n
      6, and [1-14C]20:5n-3 at 5 and at 12 degrees C were studied using cultivated
      hepatocytes from Atlantic salmon. The salmon were fed diets, in which 0, 50, or
      100% of the supplementary fish oil had been replaced by soybean oil, for 950 day
      degrees at 5 and 12 degrees C. The endogenous percentage of 18:2n-6 in hepatocyte
      lipids was 2% in cells from fish fed a diet with 100% of the supplemental lipid
      from fish oil, and it was slightly less than 25% in cells from fish fed the diet
      with 100% of the supplemental lipid from soybean oil. Furthermore, the
      percentages of 20:3n-6 and 20:4n-6 were significantly higher in hepatocytes from
      fish fed on soybean oil than they were in those of fish fed on fish oil. The
      percentages of 20:5n-3 and 22:6n-3, on the other hand, were lower. The endogenous
      levels of n-6 FA were not significantly correlated with the total amounts of
      radiolabeled FA esterified in hepatocyte lipids. The main radiolabeled products
      formed from 18:2n-6 were 20:2n-6 and 20:3n-6. The level of the important
      eicosanoid precursor 20:4n-6 was twice as high in hepatocyte phospholipids from
      fish fed the 100% soybean oil diet as it was in hepatocytes from fish fed the
      diet with 100% of supplemental lipid from fish oil. The main products formed from
      18:3n-3 were 20:4n-3, 20:5n-3, and 22:6n-3. High levels of dietary 18:2n-6 do
      allow, or even seem to increase, the production of 22:6n-3 from 18:3n-3 in
      hepatocytes. The main products formed from 20:5n-3 were 22:5n-3 and 22:6n-3. The
      production of 22:6n-3 from 20:5n-3 was higher at 5 degrees C than at 12 degrees
      C. The percentage of 24:5n-3 was higher at 5 degrees C than it was at 12 degrees
      C, as was the ratio of 24:5 to 22:5. These results suggest that the elongation
      rate of 22:5n-3 to 24:5n-3 is higher at the lower temperature.

PMID- 14577663
TI  - Pharmacological modulation of fatty acid desaturation and of cholesterol
      biosynthesis in THP-1 cells.
AB  - In THP-1 cells, simvastatin decreases, in a concentration-dependent manner,
      cholesterol synthesis and increases linoleic acid (LA) conversion to its long
      chain derivatives, in particular to arachidonic acid, activating delta6 and
      delta5 fatty acid (FA) desaturases. The intermediates in cholesterol synthesis,
      mevalonate and geranylgeraniol, partially reverse the effects of simvastatin on
      the LA conversion. The aims of this work were to evaluate: (i) the correlation
      between cholesterol synthesis and desaturase activity and (ii) the possible
      involvement of protein isoprenylation in desaturase activity, assessed through
      pharmacological treatments. THP-1 cells were incubated with [1-14C]LA or with [1
      14C]di-homo-gamma-linolenic acid (DHGLA) and treated with simvastatin or with
      curcumin and nicardipine, inhibitors of desaturases. Curcumin was more active
      than nicardipine in inhibiting LA and DHGLA conversion: 20 microM curcumin, alone
      or with simvastatin, totally inhibited delta6 and delta5 desaturation steps; 10
      microM nicardipine only partially inhibited the enzymes, being more active on
      delta5 desaturase. Simvastatin treatment decreased the incorporation of acetate
      in cholesterol (-93.8%) and cholesterol esters (-70.2%), as expected. Curcumin
      and nicardipine also decreased cholesterol synthesis and potentiated simvastatin.
      Finally, the isoprenylation inhibitors (perillic acid and GGTI-286) neither
      affected the conversion of LA nor inhibited the delta5 desaturase activity. In
      conclusion, our results indicate that there is no direct relationship between
      cholesterol synthesis and desaturase activity. In fact, simvastatin decreased
      cholesterol synthesis and enhanced LA conversion (mainly delta5 desaturation),
      whereas curcumin and nicardipin decreased delta5 desaturation, with a limited
      effect on cholesterol synthesis.

PMID- 14577664
TI  - Comparison of ex vivo inhibitory effect between 2-hydroxyestradiol and its 17
      sulfate on rat hepatic microsomal lipid peroxidation.
AB  - Two endogenous antioxidants that are speculated to be defense substances against
      preeclampsia, 2-hydroxyestradiol (2-OH-E2) and its 17-sulfate, 2-hydroxyestradiol
      17-sulfate (2-OH-E2-17-S), were administered to rats to compare their inhibitory
      effects on hepatic microsomal lipid peroxidation, and the lipid peroxides were
      determined in NADPH- and ascorbic acid-dependent systems. The two catechols
      showed a strong inhibitory effect on lipid peroxidation in both systems, and the
      effect was dose dependent. However, a large difference was observed in their
      inhibition patterns. After administration of 2-OH-E2, the effect appeared
      immediately and decreased gradually with time. In contrast, the effect of 2-OH-E2
      17-S appeared some time after administration and persisted for a longer time.
      Both catechols also showed a striking difference in their dynamics. After
      administration, 2-OH-E2 was detected in the blood together with its metabolites,
      2-methoxyestradiol and 2-methoxyestrone, and they disappeared immediately. In
      contrast, 2-OH-E2-17-S was present in the blood for a longer time together with
      its O-methylated product, 2-methoxyestradiol 17-sulfate, but disappeared from
      liver microsomes within 2 h after administration. The results imply no occurrence
      of a direct inhibition effect of 2-OH-E2-17-S.

PMID- 14577666
TI  - Synthesis of fluorinated analogs of myristic acid as potential inhibitors of
      Egyptian armyworm (Spodoptera littoralis) delta11 desaturase.
AB  - To study the activity of the different desaturases present in the pheromone
      biosynthetic pathway of the Egyptian armyworm, Spodoptera littoralis, we prepared
      a series of mono- and gem-difluorinated analogs of myristic acid with halogen
      substitution at the C8-C11 positions of the aliphatic chain via specifically
      positioned dithiane precursors. Thus, transformation of dithianes by treatment
      with N-bromosuccinimide in the presence of H2O followed by reduction with LiAlH4
      afforded the appropriate alcohols, which reacted with diethylaminosulfur
      trifluoride to give rise to the corresponding monofluoroderivative intermediates.
      Alternatively, the introduction of the gem-difluoro functionality was carried out
      by reaction of the appropriate dithiane intermediate with 1,3-dibromo-5,5
      dimethylhydantoin in the presence of HF/pyridine. The activity of these
      fluorinated FA as substrates and inhibitors of the desaturases involved in the
      biosynthesis of the sex pheromonal blend of S. littoralis has been studied. In
      this case, 11-fluorotetradecanoic acid elicited a moderate inhibitory activity of
      delta11 desaturase.

PMID- 14577665
TI  - Chemical and enzymatic transacylation of amide-linked FA of buttermilk
      gangliosides.
AB  - The goal of this work was to alter the composition of amide-linked FA of bovine
      buttermilk gangliosides, particularly the disialoganglioside GD3, to adjust lipid
      sources to special food specifications and pharmacological or cosmetic
      applications. The chemical transacylation of amide-linked FA of buttermilk
      gangliosides with free arachidic acid (20:0) by a combination of basic hydrolysis
      and diethylphosphorylcyanide/triethylamine-catalyzed reacylation was compared to
      an enzymatic sphingolipid ceramide N-deacylase (EC 3.5.1.23)-catalyzed FA
      exchange by GC analysis and nano electrospray ionization-MS. The buttermilk
      predominantly contained the disialoganglioside GD3 and the monosialoganglioside
      GM3. The heterogeneity of FA that are incorporated into gangliosides, mainly
      palmitic acid (29.4 wt%), stearic acid (16.9 wt%), oleic acid (17.8 wt%), and
      myristic acid (8.5 wt%), was effectively altered by both transesterification
      techniques. Arachidic acid, which was not integrated into the initial buttermilk
      gangliosides, was transacylated to total gangliosides with 23.2 wt% (GD3, 6.7
      wt%) by the chemical process and with 8.7 wt% (GD3, 13.8 wt%) when catalyzed
      enzymatically. Mainly behenic acid and lignoceric acid of GD3 were exchanged
      chemically, and stearic acid was exchanged by the enzymatic process. This
      observation might depend on hydrolytic sensitivities of amide-linked very long
      chain saturated FA or specific enzyme subtrate affinities, respectively. Results
      of chemical hydrolysis indicated there was a risk of sialic acid decomposition
      and unspecific degradations. Regarding specificity and avoidance of critical
      agents, the enzymatic transesterification is recommended for industrial-scale
      production of consumer goods.

PMID- 14577667
TI  - Synthesis and characterization of deoxycholyl 2-deoxyglucuronide: a water-soluble
      affinity labeling reagent.
AB  - Acyl glucuronides, which are biosynthesized by the action of
      glucuronosyltransferases to material for detoxification, are water-soluble and
      chemically active; they produce irreversible protein adducts via both the
      transacylation mechanism and the imine mechanism. The acyl group at the C-1
      position migrates from the anomeric carbon to the C-2 position of the glucuronic
      acid moiety, producing the aldehyde group at the C-1 position, where the protein
      easily condenses through a Schiff's base, in the open-chain aldose form. The
      elimination of the hydroxyl group at the C-2 position therefore may prevent a
      protein-bound adduct via the imine mechanism. In this paper, we describe the
      synthesis and characterization of an acyl 2-deoxyglucuronide of deoxycholic acid
      as a model compound to investigate its possible utility as a water-soluble
      affinity labeling reagent for lipophilic carboxylic acids. The solubility of
      deoxycholyl 2-deoxyglucuronide in an aqueous solution was sufficient under
      physiological conditions, and the desired material reacted with model peptides to
      produce covalently bound adducts only via the transacylation mechanism.

PMID- 14577668
TI  - Lipid synthesis and acyl-CoA synthetase in developing rice seeds.
AB  - Developing rice seeds rapidly accumulated storage lipids between 5 and 12 d after
      flowering. The contents of palmitic, oleic, and linoleic acids increased
      throughout seed development, while the alpha-linolenic acid content remained low.
      The activity of acyl-CoA synthetase varied coincidentally during the period of
      lipid accumulation, and rice seeds had a sufficient capacity to supply acyl-CoA
      substrates for TAG synthesis. Acyl-CoA synthetase showed a broad specificity for
      native FA of rice seeds except for stearic acid, and pi electrons of a delta9
      delta11 double bond in the C16-C18 acyl chains were required for its maximal
      activity.

PMID- 14577669
TI  - Phospholipid FA of piezophilic bacteria from the deep sea.
AB  - Phospholipid FA (PLFA) profiles were determined on four piezophilic bacteria from
      the deep sea: Moritella japonica DSK1, Shewanella violacea DSS12, S. benthica
      DB6705, and S. benthica DB21MT-2. The total concentrations of PLFA were higher in
      strains grown at low pressure (DSK1, 10 MPa, 27.0 mg/g dry wt cells; DSS12, 50
      MPa, 24.0 mg/g), and lower in strains grown at high pressure (DB6705, 85 MPa, 1.9
      mg/g; DB21MT-2, 100 MPa, 3.0 mg/g). The piezophilic bacteria were characterized
      by a high abundance of unsaturated FA (62-73% of total FA). In particular, PUFA
      were detected in all piezophiles examined. Moritella japonica DSK1 produced 22:6n
      3 (DHA), whereas the three Shewanella strains produced 20:5n-3 (EPA) with trace
      amounts of DHA. The detection of low levels of the medium-chain-length PUFA 18:2n
      6 and 18:3 (DSK1) and 20:2 (DB6705 and DB21MT-2) suggests that the biosynthesis
      of EPA and DHA may be regulated by the formation and desaturation of di- and tri
      unsaturated FA.

PMID- 14577670
TI  - Which of the n-3 FA should be called essential?

PMID- 14577671
TI  - The XYY syndrome: a follow-up study on 38 boys.
AB  - In the last decade there has been a significant increase in the proportion of XYY
      males detected prenatally, mostly as a fortuitous finding. It is of utmost
      importance to obtain a clear idea of the developmental profile of boys with
      karyotype 47,XYY and of possible problem areas during further development in
      order to inform the parents correctly during pregnancy and to provide an adequate
      surveillance later on. In this study we observed 38 XYY males, of which 12 were
      diagnosed prenatally. We found that these patients are at considerably increased
      risk for delayed language--and/or motor development. From birth on, weight,
      height and head circumference are above average values. The majority attends
      kindergarten in the normal education circuit although in 50% of the cases
      psychosocial problems are documented. From primary school age on, there is an
      increased risk for child psychiatric disorders such as autism. Moreover, although
      normally intelligent, many of these boys are referred to special education
      programmes.

PMID- 14577672
TI  - Multiple malformations in a male and maternal osteopathia strata with cranial
      sclerosis (OSCS).
AB  - Osteopathia striata with cranial sclerosis (OSCS), conductive hearing impairment
      and a characteristic facial appearance is the clinical manifestation in carrier
      women of an X-linked disease. We report on a family with typical OSCS in the
      mother, a maternal aunt and the grandmother, and multiple severe malformations in
      the son. He was affected by cranial sclerosis with frontal bossing, conductive
      hearing impairment, cleft palate, thoracic dysplasia, mesenterium commune with
      non-rotation of the gut, anal atresia, bilateral cutaneous syndactyly of 3rd and
      4th fingers, duplication of the distal phalanx of 2nd and 3rd fingers on the
      right, bilateral fibular aplasia with clubfeet, developmental retardation,
      epileptic seizures, hypothyroidism, and hypertrophic pyloric stenosis. The X
      inactivation pattern in peripheral leucocytes of one informative carrier woman
      was random. Our case and several literature reports confirm that males which are
      hemizygous for the OSCS trait suffer from a dysmorphic syndrome with
      characteristic multiple malformations as a distinct entity. There is, at present,
      no reason to assume genetic heterogeneity with an autosomal dominant OSCS
      variant.

PMID- 14577673
TI  - Multiple congenital malformations including generalized hypertrichosis with gum
      hypertrophy in a child exposed to valproic acid in utero.
AB  - Fetal valproate syndrome results from in utero exposure to valproic acid. It is
      characterized by a distinctive facial appearence, a cluster of minor and major
      anomalies, and central nervous system dysfunction. We report on a child exposed
      prenatally to valproic acid with unusual anomalies. This patient was the first
      child of young parents. Mother had several generalized seizures one year before
      this pregnancy, and since than she took valproic acid. Pregnancy was otherwise
      uneventful. At birth physical examination showed generalized hypertrichosis
      sparing palms and soles, coarse face, gum hypertrophy, hypotonia, club feet and
      club hands, two annular constrictions of the right lower leg, and abnormal
      dermatoglyphics. Skeletal X-rays were normal. Gum hypertrophy and hypertrichosis
      may be part of a broader pattern of altered morphogenesis in fetus exposed to
      valproic acid or this patient had two conditions, fetal valproate syndrome and
      hypertrichosis with gum fibromatosis.

PMID- 14577674
TI  - Expanding the phenotypic spectrum of the Baller-Gerold syndrome.
AB  - We report on two sisters off-spring of healthy consanguineous parents, where
      their major clinical features absent thumb, radial aplasia and craniosynostosis
      led to a diagnosis of Baller-Gerold syndrome BGS (OMIM:218600). Syndromes with
      associated preaxial reduction defects mainly Fanconi pancytopenia, VATER
      association, Rothmund-Thompson and Roberts phocomelia syndrome were excluded by
      proper clinical and cytogenetic studies. In addition to craniosynostosis and
      radial deficiency, our studied cases had absent or hypoplastic thumbs, postaxial
      polydactyly in the left foot, genital anomalies and orodental manifestations.
      Review of the literature depicted phenotypic variability of BGS. The presence of
      affected sibs the offspring of consanguineous parents confirms autosomal
      recessive inheritance. The observation of associated postaxial polydactyly, blue
      sclera, rotatory nystagmus, other skeletal and orodental anomalies broadened the
      spectrum of phenotypic variability. Awareness of the expanded phenotypic spectrum
      will improve the diagnosis and genetic counseling of BGS.

PMID- 14577675
TI  - Two unusual types of syndactyly in the same family; Cenani-Lenz type and "new"
      type versus severe type I syndactyly?
AB  - Cenani-Lenz syndactyly is a very rare syndrome where the syndactyly is totally
      disorganized with abnormal development of pattern formation of the hand. We
      report here an additional case of Cenani-Lenz syndactylism in a woman who has
      congenital cataract and an unusual type of duplication of big toes not described
      so far. She had a half cousin who had an unusual new type or severe type I
      syndactyly. It is not clear whether these two types of syndactyly present in this
      family may be coincidental or not.

PMID- 14577676
TI  - Pre-auricular tags and associated anomalies: considerations for genetic
      counseling.
AB  - Pre-auricular tags are relatively common isolated congenital anomalies with a
      prevalence of about 5 per 1000 live births. Several associations with congenital
      anomalies have been reported and the opportunity of systematic ultrasonography
      examinations in these patients were debated in the literature. We conducted a
      retrospective epidemiological study on 95 affected newborns, to evaluate whether
      infants with pre-auricular tags may be at risk for associated anomalies. Our
      results focus the attention on the increased risk of congenital urinary tract and
      heart malformations in newborns with isolated pre-auricular tags. Therefore, we
      recommend that a carefully genetic clinical examination to evaluated dysmorphic
      features evocative of a specific pattern or syndrome and an urinary and cardiac
      ultrasonography should be performed in infants with isolated pre-auricular tags.

PMID- 14577677
TI  - Associated anomalies in asymmetric crying facies and 22q11 deletion.
AB  - Congenital asymmetric crying facies, a minor congenital anomaly due to unilateral
      absence or hypoplasia of the depressor anguli oris muscle, is associated at times
      with major congenital anomalies. A large number of asymmetric crying facies cases
      with chromosome 22q11 microdeletions have presently been reported. Fluorescence
      in situ hybridization (FISH) analysis for 22q11 deletion was performed on 8
      infants with asymmetric crying facies. Five of our patients had at least one
      associated systemic anomaly. Two of 5 patients had conotruncal heart disease
      (Cayler cardiofacial syndrome). In three of the affected infants, we failed to
      reveal additional congenital malformation. The 22q11 deletion was present in only
      one patient. This baby had congenital hypoparathyroidism, severe neonatal
      hypocalcaemia and tetralogy of Fallot. We suggest, a 22q11 deletion should be
      excluded not in all cases but in cases with Cayler cardiofacial syndrome and in
      ACF associated with additional congenital anomalies.

PMID- 14577678
TI  - A prenatal counseling conundrum: mosaic trisomy 16. A case study presenting
      cognitive functioning and adaptive behavior.
AB  - We report developmental data on a patient prenatally diagnosed with mosaic
      trisomy 16. At age six years her intellectual functioning, academic achievement,
      and adaptive behavior are normal. The myriad of findings among cases prenatally
      diagnosed with mosaic trisomy 16 are discussed. The diagnosis presents a dilemma
      for genetic counselors and clinicians.

PMID- 14577679
TI  - A girl with cutaneous hyperpigmentation, cafe au lait spots and ring chromosome
      15 without significant deletion.
AB  - Ring chromosome 15 [r(15)] syndrome is characterised by specific facial features,
      cafe au lait spots, failure to thrive, mental retardation and typically with a
      terminal deletion of the long arm of chromosome 15. We report a 2.5 year old girl
      showing normal growth and development, large hyperpigmented skin changes showing
      hypopigmentated areas inside, multiple cafe au lait spots and premature graying
      like hypopigmentation of scalp hair. She had a karyotype of r(15) in peripheral
      lymphocytes and fibroblasts. By FISH analysis the breakpoint was located distal
      to locus D15S936 (15q26.3) and within 300 kb of the end of the chromosome,
      indicating no deletion of functional genes on 15q. Hyperpigmentation and cafe au
      lait spots are rare signs in ring chromosome syndromes, but with r(15) syndrome,
      cafe au lait spots have been described in about 30% of patients and have been
      considered to result from the deletion of gene(s) on distal 15q. Based on the
      frequent observation of patchy hyperpigmentation with the r(15) syndrome, absent
      hyperpigmentation in cases of distal 15q deletion without a ring chromosome, and
      the telomeric breakpoint location in our patient indicating no significant
      deletion, we propose that the cutaneous hyperpigmentation and cafe au lait spots
      in our proband represent effects of the r(15) chromosome but are not caused by
      the deletion of specific gene(s) on distal 15q. Patchy skin hypopigmentation is a
      well known nonspecific sign in cytogenetic mosaicism which is commonly seen in
      ring syndrome.

PMID- 14577680
TI  - A Turkish case of subcortical/subependymal heterotopia associated with corpus
      callosum dysgenesis, craniofacial dysmorphism, severe eye abnormalities, and
      growth-mental retardation.
AB  - The patient is a 12-year-old boy with a history of learning disability, growth
      retardation, and strabismus. Weight, height and head circumference were below the
      3rd percentile. A cafe-au-lait spot, 1x1 cm a diameter, on the back region and
      pectus excavatum deformity were diagnosed. He had facial asymmetry, a broad nose,
      sparse eyebrows and eyelashes, a rudimentary frontal sinus, deviation of the
      nasal septum, and bilateral small maxillary bones. The left orbital fossa was
      also mildly rudimentary. On eye examination the movements of the left globe to
      the upward and lateral side were limited and internal strabismus was noted at
      this side. Visual acuity was 1/10, bilaterally. Bilateral choroid coloboma,
      glaucoma, vertical and horizontal nystagmus were diagnosed. Fundoscopic
      examination revealed bilateral optic atrophy and macular and paramacular
      granulation tissues on the left side. Intelligence quotient was 46.
      Electroencephalography revealed bilateral frontal slow-wave activity. Visual
      evoked potential revealed prolonged p100 wave latencies bilaterally. Magnetic
      resonance imaging of the brain demonstrated corpus callosum dysgenesis, bilateral
      subcortical heterotopia in the frontal lobes and subependymal heterotopia in the
      posterior horn of the left ventricle. Chromosomal analysis revealed a normal male
      karyotype, 46, XY. Although several cases of heterotopia in association with
      mental retardation, craniofacial dysmorphism, cerebral, and eye abnormalities
      have been described the combination of abnormalities diagnosed in our case has
      not previously been reported. We hypothesize that the combination of
      subcortical/subependymal heterotopia, corpus callosum dysgenesis, craniofacial
      dysmorphism, severe eye abnormalities, and growth-mental retardation may be a new
      syndrome.

PMID- 14577681
TI  - Superior sternal cleft and minor hemangiomas in a newborn.
AB  - The association of hemangioma and sternal cleft is rare. It may present as
      sternal malformation/vascular dysplasia association or PHACES syndrome when
      associated with other ventral developmental defects. We report on a newborn
      infant with superior sternal cleft and minor hemangiomas.

PMID- 14577682
TI  - Schwartz-Jampel syndrome: three pediatric case reports.
AB  - Schwartz-Jampel syndrome is a heterogeneous autosomal recessive syndrome defined
      by myotonia, short stature, bone dysplasia and growth retardation. Three types
      have been described: type 1A, usually recognized in childhood, with moderate bone
      dysplasia; type 1B similar to type 1A but recognizable at birth, with more
      prominent bone dysplasia and type 2, a rare, more severe form with increased
      mortality in the neonatal period. In this paper we report three pediatric cases,
      one with neonatal manifestation.

PMID- 14577683
TI  - Distal 10q trisomy associated with bilateral hydronephrosis in infancy.
AB  - We present clinical and cytogenetic data on a 2.5 year-old boy with partial
      monosomy 22p (p11.2-->pter) and distal 10q trisomy (10q24.1-->qter), resulting
      from maternal t(10;22) reciprocal translocation. The patient had bilateral
      hydronephrosis and hydroureters but without evidence of vesicoureteral reflux.
      Our clinical observation suggests that urinary collecting system anomaly may be
      an integral part of distal 10q trisomy syndrome. We recommend detailed imaging
      studies of urinary tracts be performed on probands with chromosomal disorders
      involving a duplication of distal 10q.

PMID- 14577684
TI  - Gaucher disease and brucella: just a mere coincidence?
AB  - Gaucher disease type I and brucellosis are chronic diseases with similar symptoms
      and physical signs though the former is the most common lysosomal storage disease
      and the latter is an infectious disease. The similarities between these diseases
      make differential diagnosis difficult. Immunodeficiency is a feature of Gaucher
      disease type I and increases the susceptibility towards infections. A Gaucher
      disease type I patient with brucellosis is presented with improvement after
      treatment of brucellosis.

PMID- 14577685
TI  - Middle and inner ear anomalies in a patient with CHARGE association.

PMID- 14577686
TI  - Anti-oxidative activity of glycosides from Ligustrum sinense.
AB  - Three active glycosides that afford protection to red blood cell membrane to
      resist hemolysis induced by a peroxyl radical initiator, 2,2'-azo-bis-(2
      amidinopropane) dihydrochloride (AAPH) were isolated from the MeOH extract of
      Ligustrum sinense. The compounds are 10-hydroxyl-oleuropein (1), 3-O-alpha-L
      rhamnopyranosyl-kaempferol-7-O-beta-D-glucopyranoside (4), and 8'-alpha-hydroxyl
      lariciresinol-4'-O-beta-D-glucopyranoside (6). The structures of these glycosides
      were determined by 1D and 2D NMR spectral analysis.

PMID- 14577687
TI  - Microbial transformation of cortisol and prolyl endopeptidase inhibitory activity
      of its transformed products.
AB  - Incubation of cortisol (1) with Gibberella fujikuruoi for 12 days yielded an
      oxidatively cleaved product, 11beta-hydroxyandrost-4-en-3,17-dione (2), while
      incubation with Bacillus subtilis and Rhizopus stolonifer yielded the reduced
      product, 11beta, 17alpha,20,21-tetrahydroxy-(20S)-pregn-4-en-3-one (3). Other
      reduced products, 11beta, 17alpha, 21-trihydroxy-5alpha-pregnan-3, 20-dione (4)
      and 3beta, 11beta, 17alpha, 21-tetrahydroxy-5alpha-pregnan-20-one (5) were
      obtained by incubation of compound 1 with Bacillus cerus. The inhibitory activity
      of compounds 1-5 against prolyl endopeptidase enzyme (PEP) was also assayed.
      Compounds 2 (IC50 162.8 microM) and 4 (IC50 157 microM) have shown significant
      inhibitory activity against PEP.

PMID- 14577688
TI  - Two new alkaloids from Miliusa cuneata.
AB  - Two new isoquinoline alkaloids, 2,10-dimethoxy-3,11-dihydroxy-5,6
      dihydroprotoberberine (1) and 1,9-dihydroxy-2,11 -dimethoxy-4,5-dihydro-7
      oxoaporphine (2), together with thirteen known alkaloids, were isolated from the
      ethanolic extracts of the stem and leaves of Miliusa cuneata (Graib). Their
      structures were elucidated predominantly by spectral evidence.

PMID- 14577689
TI  - Antioxidant capacity of flavonoids and a new arylphenol of the resinous exudate
      from Heliotropium sinuatum.
AB  - From the resinous exudate of Heliotropium sinuatum (family Boraginaceae), a new
      compound: 4-(3',5'-dihydroxynonadecyl)phenol 1, together with eight previously
      described flavonoids, were isolated and their antioxidant activities were
      assessed by quenching measurements with ABTS and DPPH cation radicals.

PMID- 14577690
TI  - New cembranolide analogues from the formosan soft coral Sinularia flexibilis and
      their cytotoxicity.
AB  - Using a bioactivity-guided fractionation procedure, five cembranolides, 11-epi
      sinulariolide acetate (1), 11-dehydrosinulariolide (2), sinulariolide (3),
      dihydrosinularin (4), and 3,4:8,11-bisepoxy-7-acetoxycembra-15(17)-en-1,12-olide
      (5), along with two nucleosides, 2'-deoxyadenosine and thymidine, were isolated
      from the Formosan soft coral Sinularia flexibilis. Moreover, 7,8-epoxy-11-epi
      sinulariolide acetate (1a), 11-sinulariolide acetate (3a), dihydrosinulariolide
      (3b), 3,4:8,11-bisepoxy-7-hydroxycembra-15(17)-en-1,12-olide (3c), 11-acetoxyl
      15(17)-dihydrosinulariolide (3d), 7,8-epoxy-11-sinulariolide acetate (3e), and
      3,4:8,11-bisepoxy-7-hydroxycembra-15(17)-dihydro-1,12-olide (3f) were derived
      from compounds 1 and 3, respectively. These structures were deduced on the basis
      of physical and chemical evidence. Among them, 1a, 3d, 3e, and 3f are new
      cembranolide analogues. The structure of compound 1 was further confirmed by X
      ray analysis. In addition, the isolated cembranolides and the analogues under
      went a cytotoxicity assay, and the structure-activity relationship (SAR) of these
      compounds was studied.

PMID- 14577691
TI  - Microwave-assisted rapid synthesis of methyl 2,4,5-trimethoxyphenylpropionate, a
      metabolite of Cordia alliodora.
AB  - Microwave assisted condensation of asaronaldehyde (2) with malonic acid in
      piperidine-AcOH provides 2,4,5-trimethoxycinnamic acid (3) in 87% yield within 4
      min, which upon further reduction with PdCl2- HCOOH-aq. NaOH gives 3-(2,4,5
      trimethoxy)phenyl propionic acid (4) in 88% yield within 3 min. Esterification of
      4 with MeOH-H+ gives methyl 2,4,5-trimethoxyphenylpropionate (1), a metabolite of
      Cordia alliodora, in 94% yield within 3 min (overall 69% yield).

PMID- 14577692
TI  - A new lignan from the seeds of Sphaerophysa salsula.
AB  - A novel lignan: sphaerophyside SC was isolated from ethanolic extract of the
      seeds of Sphaerophysa salsula (Pall.) DC. The structure of the compound was
      elucidated mainly on the basis of the 1D NMR and 2D NMR data.

PMID- 14577693
TI  - A new isocoumarin from bark of Pellodendron chinense.
AB  - A new isocoumarin, 3-acetyl-3,4-dihydro-5,6-dimethoxy-1H-2-benzopyran-1-one, was
      isolated from the cortex of Phellodendron chinense schneid. The structure was
      determined on the basis of spectroscopic evidences.

PMID- 14577694
TI  - 7, 8-dihydroxyflavanone as an inhibitor for Jun-Fos-DNA complex formation and its
      cytotoxic effect on cultured human cancer cells.
AB  - 7,8-Dihydroxyflavanone, isolated from the seeds of Alpinia Katsumadai Hayata,
      showed an inhibitory effect on Jun-Fos dimer action. 7,8-Dihydroxyflavanone
      blocked the action of the dimer on a DNA consensus sequence, the AP-1 binding
      site. We have concluded that the Jun-Fos heterodimer, bound with 7,8
      dihydroxyflavanone, cannot bind to the AP-1 site and therefore results in signal
      interruption. The 7,8-dihydroxyflavanone was also found to have an in vitro
      cytotoxic effect against A549 (a human lung cancer cell line) and K562 (a human
      leukemia cell line).

PMID- 14577695
TI  - Alkaloids from Croton flavens L. and their affinities to GABA-receptors.
AB  - Phytochemical investigation of several plants of Croton flavens L. from Barbados
      has led to the isolation of the tetrahydroprotoberberine alkaloids scoulerine and
      coreximine, as well as the morphinanedienones salutaridine and its racemic form
      salutarine, sebiferine, norsinoacutine and flavinantine. In a screening for 3H
      GABA displacing activity coreximine showed the highest affinity to the GABA(A)
      receptor.

PMID- 14577696
TI  - Monoterpenes produced by Cupressus lusitanica cultured cells including a novel
      monoterpene (1R, 2S, 6S)-(+)-1,6-epoxy-4(8)-p-menthen-2-ol [corrected].
AB  - A novel monoterpene,(1R, 2S, 6S)-(+)-1,6-epoxy-4(8)-p-menthen-2-ol [corrected],
      was isolated from an elicitor-treated cell culture of Cupressus lusitanica
      (Mexican cypress). Ten known monoterpenes--limonene, myrcene, beta-ocimene,
      sabinene, terpinolene, 4-terpineol, alpha-terpineol, 4(8)-p-menthen-1,2-diol, 4
      hydroxyphellandric acid methylester and beta-thujaplicin methylether--were also
      identified. Regioselective metabolisms of monoterpenes were observed in this
      culture.

PMID- 14577697
TI  - A new xanthone from Hedychium gardnerianum.
AB  - A new xanthone (2), 3-(2-hydroxyethoxy)xanthone, and three known compounds, 1
      hydroxyxanthone, salicylic acid and the sesquiterpene oplopanone, were isolated
      for the first time from the rhizomes of Hedychium gardnerianum Rosc. The
      structures of these compounds were elucidated on the basis of detailed spectral
      analysis, including 2D NMR experiments.

PMID- 14577698
TI  - New 2-o-methylrhamno-isoflavones from Streptomyces sp.
AB  - Chemical screening with extracts of Actinomycetes strains resulted in the
      detection, isolation and structure elucidation of five new isoflavone glycosides
      from Streptomyces sp. (GT 51173): 5-O-alpha-L-rhamnopyranosyl genestein
      (genestein G1, 1), 5-O-alpha-L-rhamnopyranosyl-7-O-[2-O-(methyl)-alpha-L
      rhamnopyranosyl] genestein (genestein G2, 2), 7,4'-O-di-[2-O-(methyl)-alpha-L
      rhamnopyranosyl] daidzein (daidzein G1, 3), 6-O-methyl-7-O-[2-O-(methyl)-alpha-L
      rhamnopyranosyl] daidzein (daidzein G2, 4) and 7-O-[2-O-(methyl)-alpha-L
      rhamnopyranosyl] daidzein (daidzein G3, 5). As a striking structural feature, 2-5
      bear one or two alpha-L-rhamnopyranosyl sugar moieties with methoxy groups in an
      axial position at C-2.

PMID- 14577699
TI  - Triterpenoids from the stembark of Pyrus communis.
AB  - Three triterpenoids were isolated from the stem bark of Pyrus communis Linn. and
      identified as lup-20(29)-ene-3alpha, 27-diol (1), lup-20(29)-ene-3alpha-ol (2)
      and lup-20(29)-ene-3alpha, 28-diol (3) on the basis of spectral and chemical
      analysis. The Compound (1) is a novel triterpene, being reported first time by
      us.

PMID- 14577700
TI  - Canadian surgery and the events of 2003.

PMID- 14577701
TI  - Error and surgery: can we do better?

PMID- 14577702
TI  - October 2003, 25th anniversary of the Canadian Society for Vascular Surgery.

PMID- 14577703
TI  - Perioperative stroke occurring in patients who undergo neck dissection for head
      and neck cancer: unanswered questions.
AB  - Stroke represents a major cause of disability among middle-aged and elderly
      people. Carotid artery stenosis is an important risk factor for stroke and is
      prevalent in elderly men with hypertension, diabetes mellitus, and those who
      smoke or have atherosclerotic disease, or both. Patients who undergo neck
      dissection for head and neck cancer may have some or all of the above
      characteristics and may experience surgical manipulation of the carotid arteries.
      This combination of medical and surgical factors may predispose such patients to
      perioperative stroke. A critical review of the literature was completed to
      determine the incidence of stroke perioperatively in patients undergoing a neck
      dissection for head and neck cancer. We found 2 studies that quoted the risk of
      stroke to be between 3.2% and 4.8%. The implications of these results are
      significant because they suggest a need for preoperative screening (with Doppler
      ultrasonography) or intervention (with carotid endarterectomy), or both. However,
      the quality of these 2 studies is such that future research is first needed to
      define the rate of stroke in head and neck surgery.

PMID- 14577704
TI  - General surgery in a district hospital in Tajikistan: clinical impact of a
      partnership between visiting volunteers and host specialists.
AB  - After the collapse of the Soviet Union and 5 years of civil war, health care
      services in Tajikistan are in disarray. Nongovernmental organizations are playing
      a key role in recovery programs. A group of volunteer physicians from the West
      went to Khorog General Hospital in the Pamiri mountains to establish a dialogue
      with their physician counterparts, recommend evidence-based best practice
      appropriate for local conditions, and reintroduce a culture of continuing medical
      education. The arrangements included a group visit to Khorog for 3 weeks annually
      over 3 years. In this article we describe the experiences of the 2 general
      surgeons attached to the group in the second year and the status of the
      partnership 1 year later.

PMID- 14577705
TI  - Laparoscopic adrenalectomy: pathologic features determine outcome.
AB  - INTRODUCTION: The differential outcomes of laparoscopic adrenalectomy are not
      well described. Therefore, we evaluated these outcomes in the 3 groups most often
      seen clinically: bilateral adrenalectomy for Cushing's disease (group 1),
      pheochromocytoma (group 2) and unilateral adrenalectomy for non-pheochromocytoma
      (group 3). METHODS: We reviewed a longitudinal database of 72 consecutive cases
      of laparoscopic adrenalectomy carried out between 1997 and 2001 at the Centre for
      Minimally Invasive Surgery, University of Toronto. RESULTS: Patients in group 1
      tended to be older (median 49 yr) and heavier (median 87 kg). They had a longer
      operating time (median 255 min), more postoperative complications (15%) and a
      longer median postoperative stay (4 d). Patients in group 2 had intermediate
      outcomes: a median operating time of 198 minutes, complication rate of 8.3% and a
      median postoperative hospital stay of 3 days. However, they had more
      intraoperative blood loss (median 150 mL). Group 3 patients had the best outcomes
      with the shortest median operating time (125 min), least blood loss (median 50
      mL), fewer complications (6%) and shortest hospital stay (median 2 d).
      CONCLUSIONS: Although the outcomes of laparoscopic adrenalectomy are uniformly
      good, on the basis of the underlying pathologic characteristics, patients can be
      divided into groups that have different expected outcomes. Patients requiring a
      unilateral adrenalectomy except for pheochromocytoma have the best recorded
      outcomes. Surgeons transferring to laparoscopic adrenalectomy would benefit from
      selecting patients in this group during their learning curve.

PMID- 14577706
TI  - Anorectal malignant melanoma: treatment with surgery or radiation therapy, or
      both.
AB  - INTRODUCTION: Anorectal malignant tumours are increasing in frequency for unknown
      reasons. Surgery is the principal treatment, and the role of adjuvant therapy has
      not been defined. We therefore decided to review the experience of the Princess
      Margaret Hospital in Toronto, a large tertiary care cancer hospital, with respect
      to the surgical management of anorectal melanoma. METHODS: We reviewed the charts
      of all registered patients with anorectal malignant melanoma (AMM) treated with
      surgery or radiotherapy, or both, at the hospital between 1980 and 1999, paying
      particular attention to survival, and local and distant recurrences. RESULTS:
      There were 14 patients, all of whom were followed up to the time of death or for
      a minimum of 28 months for surviving patients. The mean ages at diagnosis were 56
      years for men and 68 years for women. Clinical staging was as follows: local, 10
      patients; locoregional, 3 patients and metastatic disease, 1 patient. Local
      therapy included local resection alone in 7 cases and abdominoperineal resection
      in 7. Seven patients received pelvic irradiation at some time during their
      disease, using different doses and fractionation schemes. Three of them had
      concomitant chemotherapy and radiotherapy with no tumour regression. In all 3
      patients the lesions was reclassified as AMM and the patient underwent surgery.
      The other 4 patients had a short course of radiotherapy for palliation after the
      original lesion recurred. The overall median survival was 12 (range from 3-51)
      months. Two patients remained alive at last follow-up. Patients managed by local
      excision had a median survival of 12 (range from 3-51) months, and those managed
      by abdominoperineal resection had a median survival of 7 (range 5-51) months. Of
      the 10 patients treated initially with local excision, 6 required reoperation.
      Three underwent salvage abdominoperineal resection. Six patients were alive 1
      year after treatment (median survival 32.5 mo [range from 21-51 mo]). Eight
      patients had a rapid evolution of their disease with a median survival of 5.5
      (range from 3-12) months. Eleven of the 12 patients who died had metastatic
      disease. CONCLUSIONS: Systemic dissemination is almost universal in patients with
      AMM. The overall survival was poor regardless of local treatment. There was a 60%
      failure rate of local excision, which necessitated further surgery. Improving
      local control is important since some patients will survive up to 3 years.

PMID- 14577707
TI  - Discoid meniscus in children: treatment and outcome.
AB  - INTRODUCTION: Discoid meniscus is an atavistic anomaly in which the meniscus of
      the knee, predominantly the lateral meniscus, is discoid rather than semilunar in
      shape. The abnormality is diagnosed relatively infrequently and may even go
      unrecognized or be untreated. Treatment has consisted of either partial or
      complete meniscectomy performed either arthroscopically or by open arthrotomy.
      Our purpose was to examine the outcome of treatment for discoid meniscus in
      children. METHODS: Since 1974, 34 children, including 2 with bilateral
      involvement, have been treated for discoid meniscus at the Children's Hospital of
      Eastern Ontario, a major pediatric referral centre. The average age of the
      children at the time of surgery was 11 years 4 months (range from 6 yr 2 mo-18 yr
      6 mo). The average follow-up was 3 years (range from 1 mo-22 yr). The lateral
      meniscus was affected in 35 of the 36 knees. Treatment consisted of partial
      resection in 19 cases, complete resection in 13; 4 did not undergo resection.
      RESULTS: There were 16 excellent, 10 good, 6 fair and 4 poor results at the time
      of most recent follow-up. In 2 cases degenerative changes were evident
      radiologically. CONCLUSION: Partial resection of discoid menisci is preferable in
      children, but in complete dislocation of the entire menisci, total removal is
      necessary.

PMID- 14577708
TI  - Surgical images: Soft tissue obstructing colon carcinoma in an irreducible
      scrotal hernia.

PMID- 14577709
TI  - Radiology for the surgeon: musculoskeletal case 30. Osteochondritis dissecans of
      the medial femoral condyle.

PMID- 14577710
TI  - Surgical Education and Self-assessment Program (SESAP). Category 11, item 9.

PMID- 14577711
TI  - International surgery: definition, principles and Canadian practice.
AB  - This article is dedicated to the Canadian international surgeon, Norman Bethune
      (1890-1939). International surgery is defined as a humanitarian branch of
      medicine concerned with the treatment of bodily injuries or disorders by incision
      or manipulations, emphasizing cooperation and understanding among nations and
      involving education, research, development and advocacy. In this article I review
      the colonial past, the dark ages following the Declaration of Alma-Ata, the
      progress made and the present challenges in international surgery. I present a
      definition of international surgery that recognizes the current era of surgical
      humanitarianism, validates a global understanding of surgical issues and promotes
      cooperation among nations. Included are the principles of international surgery:
      education, research, infrastructure development and advocacy. International
      surgical projects are classified according to type (clinical, relief,
      developmental) and integration strategy (vertical or horizontal). Also reviewed
      are the Canadian practice of international surgery by nongovernmental,
      professional and academic organizations and the requirements of international and
      Canadian funding agencies, the development concepts basic to all projects,
      including results-based management and the cross-cutting themes of gender equity,
      environmental protection and human safety. I recommend formalizing international
      surgery into a discipline as a means of promoting surgical care in low-income
      countries. If international surgery is to be sustained in Canada, infrastructure
      and support from Canadian surgeons is particularly important. An understanding of
      the history, definition and classification of international surgery should
      promote surgical care in low-income countries.

PMID- 14577713
TI  - Canadian Association of General Surgeons Evidence Based Reviews in Surgery. 7.
      Quality of life after bile duct injury during laparoscopic cholecystectomy.

PMID- 14577712
TI  - Occult pneumothorax in the mechanically ventilated trauma patient.
AB  - The term occult pneumothorax (OP) describes a pneumothorax that is not suspected
      on the basis of clinical examination or plain radiography but is ultimately
      detected with thoracoabdominal computed tomography (CT). This situation is
      increasingly common in trauma care with the increased use of CT. The rate is
      approximately 5% in injured people presenting to hospital, with CT revealing at
      least twice as many pneumothoraces as suspected on plain radiography. Whereas
      pneumothorax is a common and treatable cause of mortality and morbidity, there is
      substantial disagreement regarding the appropriate treatment of OP. The greatest
      controversy is in patients in the critical care unit who require positive
      pressure ventilation. There is little current evidence to direct the proper
      management of ventilated trauma patients with OP, and no studies have focussed
      specifically on these patients. Future randomized trials will need to consider
      the potential effects of OP on pulmonary mechanics and potential influences on
      the known risks of ventilator-induced lung injury associated with mechanical
      ventilation.

PMID- 14577714
TI  - Late neurologic deterioration after nonoperative treatment of a Chance fracture
      in an adolescent.

PMID- 14577716
TI  - Spontaneous rectus sheath hematoma.

PMID- 14577715
TI  - Endovascular stent-graft for blunt thoracic aortic rupture: a novel and useful
      approach in selected cases.

PMID- 14577717
TI  - Defining and characterizing the late-stage biopharmaceutical pipeline.
AB  - OBJECTIVE: To identify and describe biopharmaceuticals in late-stage development
      in the United States and to understand their implications for third-party payers.
      STUDY DESIGN AND METHODS: "Biopharmaceutical" and biopharmaceuticals in late
      stage US development (had completed Phase 2 or higher) were identified through
      reviews of literature, 4 drug-development databases, a clinical trial database,
      and informal telephone conversations with representatives of the US Food and Drug
      Administration, faculty at academic institutions, and manufacturers. RESULTS:
      "Biopharmaceutical" was defined as "any biology-based therapeutic that
      structurally mimics compounds found within the body." This includes recombinant
      proteins, monoclonal and polyclonal antibodies, peptides, antisense
      oligonucleotides, therapeutic genes, and certain therapeutic vaccines. As of
      April 2003, there were 102 unique biopharmaceuticals in late-stage development
      for 156 indications in 36 disease categories, affecting at least 22 distinct
      physician specialties. Cancer agents are most common, with 30 agents (29%)
      targeting 62 indications (40%). Nearly 90% of the biopharmaceuticals require
      administration via injection or infusion, nearly 70% will require administration
      by a healthcare provider, and more than 60% will be administered in ambulatory
      care settings. All 22 physician specialties are affected by healthcare provider
      administered biopharmaceuticals. Excluding cancer-related biopharmaceuticals, 60%
      of biopharmaceuticals and 54% of indications require chronic administration. Up
      to 81 biopharmaceuticals for 123 indications may be approved within the next 4
      years (including secondary approvals). CONCLUSIONS: The broad range of the late
      stage US biopharmaceutical pipeline has significant implications for third-party
      payers due to their likely premium price, once approved, as well as novel
      logistical considerations. Payers must prepare for a wide range of clinical,
      administrative, delivery, and economic issues.

PMID- 14577718
TI  - Treatment compliance and dosage administration among rheumatoid arthritis
      patients receiving infliximab, etanercept, or methotrexate.
AB  - OBJECTIVE: To examine treatment compliance and dosage administration associated
      with infliximab, etanercept, and methotrexate therapy for rheumatoid arthritis
      (RA). STUDY DESIGN: Retrospective analysis using administrative and claims data
      from a large US health plan. PATIENTS AND METHODS: Patients were Medicare or
      commercial enrollees in a health plan with a pharmacy benefit and had a diagnosis
      of RA. The first (index) claim for infliximab, etanercept, or methotrexate
      occurred between July 1, 1998, and December 31, 2000. Continuous enrollment in
      the plan was required from 182 days before to 365 days after the index claim.
      Treatment groups were compared according to compliance (defined as the actual
      number of therapy administrations or filled prescriptions divided by the expected
      number) and changes in dosage administration over time. The costs of infliximab
      therapy also were explored. RESULTS: A total of 2662 patients (infliximab = 141;
      etanercept = 853; and methotrexate = 1668) were included in the analyses.
      Infliximab patients were older and more likely to have a Medicare benefit. In
      addition, infliximab patients had more comorbidities and had greater medical
      costs preceding the index claim. Compliance with at least 80% of the expected
      dosages was significantly lower for etanercept (odds ratio [OR] 0.462; 95%
      confidence interval [CI] 0.290-0.736) and methotrexate (OR 0.385; 95% CI 0.245
      0.604) patients than infliximab patients. Methotrexate patients had the largest
      dosage increases (61.6%), followed by infliximab (37.4%) and etanercept (7.4%)
      patients. Assuming 6.5 dosages per year, the annual cost of infliximab was
      dollars 10446 to dollars 12363, or dollars 1887 to dollars 1902 per
      administration, depending on site of service. CONCLUSIONS: Compliance is higher
      with infliximab compared with etanercept or methotrexate; whereas, fewer
      etanercept patients change dosages. The cost of infliximab was lower than
      expected based on previous predictions, even with a 37% increase in dosage.

PMID- 14577720
TI  - The duPont kyphosis brace for the treatment of adolescent Scheuermann kyphosis.
AB  - The purpose of this study was to evaluate the effectiveness of a newly designed
      brace in the treatment of adolescent Scheuermann thoracic kyphosis. Twenty-two
      children who met the roentgenographic criteria of Scheuermann kyphosis and were
      compliant with treatment were followed until skeletal maturity. Sixteen patients
      (73%) showed nonprogression of their kyphosis (nine patients demonstrated an
      improvement, seven patients remained unchanged), and had a mean improvement of 9
      degrees (64 degrees to 55 degrees). Six patients (27%) demonstrated progression
      of the kyphosis and had a mean increase in their kyphosis of 9 degrees (59
      degrees to 68 degrees). One patient underwent posterior spinal fusion for
      progressive thoracic kyphosis despite bracing. It was recommended that this brace
      be worn until skeletal maturity; in this study this time period was determined to
      be at least 16 months to induce improvement or halt progression of this disease.
      Flexible curves are a positive predictor of a successful outcome of bracing with
      the kyphosis brace. These results are comparable to previous reports in the
      literature describing the effectiveness of the modified Milwaukee brace in the
      treatment of Scheuermann thoracic kyphosis prior to skeletal maturity, and the
      kyphosis brace has the advantage of concealability under normal attire.

PMID- 14577719
TI  - Recurrence of equinus foot deformity in cerebral palsy patients following
      surgery: a review.
AB  - Although equinus deformity in children with cerebral palsy is often corrected
      with surgery, postsurgical recurrence of the deformity is not uncommon. In order
      to isolate factors that may be related to its recurrence, 31 studies were
      evaluated. Data from nine articles indicated that children younger than
      approximately 7 years of age at the time of surgery had a higher risk of
      recurrence than children who were older at the time of surgery. Recurrence rates
      may be understated in studies including less than a minimum of 4-5 years of
      patient follow-up. Lower recurrence rates are documented in diplegic patients
      compared with hemiplegic patients, and postoperative casting/splinting is stated,
      but not documented, to reduce recurrence. One study demonstrated that the use of
      chemodenervation delayed surgery and by inference theoretically would decrease
      recurrence after surgical release.

PMID- 14577721
TI  - Osteoid osteoma of scaphoid.
AB  - Osteoid osteoma is infrequently localized to the hand. Initially the lesion may
      cause nonspecific symptoms. A 14-year-old boy presented with spontaneous onset
      swelling and pain wrist for 2 months. Initially he was suspected of having
      tuberculosis, but radiographs revealed a sclerotic lesion of the scaphoid and the
      sedimentation rate was not high. CT scan of the wrist showed a double-ring sign,
      indicating osteoid osteoma. Lesion was curetted and the nidus excised. This
      resulted in rapid resolution of the symptoms.

PMID- 14577722
TI  - A biomechanical comparison of suture constructs used for coracoclavicular
      fixation.
AB  - There is no consensus regarding surgical treatment for severely dislocated
      acromioclavicular joints. Although many treatments are suture-based, the suture
      materials and resulting suture-bone constructs have been subjected to limited
      systematic evaluation. This study identifies the strongest and least deforming
      suture construct among those commonly used for such repairs. Each suture-based
      repair was tested on a simulated clavicle and coracoid process with the skeletal
      components distracted until the suture failed to obtain tensile strength.
      Additional groups of sutures were subjected to cyclic loading to determine
      resistance to deformation. Panacryl braid had significantly greater tensile
      strength than all other constructs: Polydioxanone (PDS) braid, Mersilene tape,
      and Ethibond #5. Deformation after cyclic loading of Panacryl braid, PDS braid,
      and two strands of Mersilene tape was significantly less than that of the other
      constructs. A bioabsorbable suture loop, such as Panacryl, can act as a temporary
      internal splint, maintaining acromioclavicular joint reduction long enough for
      ligamentous healing during rehabilitation, and can avoid complications associated
      with permanent fixation materials. Panacryl braid deserves serious consideration
      for coracoclavicular fixation because of its strength, resistance to deformation,
      and bioabsorbable properties.

PMID- 14577723
TI  - Sagittal knee kinematics following combined hamstring lengthening and rectus
      femoris transfer.
AB  - The purpose of this study was to review knee kinematics following combined
      hamstring lengthening and rectus femoris transfer. Previous findings reported in
      the literature include kinematic changes in the magnitude of stance-phase maximum
      knee flexion, stance-phase minimum knee flexion (extension), and swing-phase
      maximum knee flexion; the timing of swing-phase maximum knee flexion and swing
      phase minimum knee flexion (extension); and total knee excursion. Twenty-three
      children underwent bilateral (22) or unilateral (1) hamstring lengthening and
      rectus femoris transfer (45 knees) at the Shriners Hospitals for Children in
      Lexington, KY between January 1996 and December 2001. Sagittal knee kinematic
      data were obtained as part of a complete gait study accomplished before surgery
      and at 1 year after surgery. Values were compared using a paired t test method
      set at a p < .05 level to determine statistical significance. Changes were seen
      in the magnitude of stance-phase maximum knee flexion, stance-phase minimum knee
      flexion (extension), swing-phase maximum knee flexion, and swing-phase minimum
      knee flexion (extension); in the timing of swing-phase maximum knee flexion; and
      in total knee excursion.

PMID- 14577724
TI  - Distal interphalangeal joint arthrodesis: treatment with Herbert screw.
AB  - From 1996 to 2000, 20 patients with a mean age of 53 underwent 20 arthrodeses
      with Herbert screws. There were 16 (80%) distal interphalangeal joint (DIP) and 4
      (20%) thumb interphalangeal (IP) joint arthrodeses. Average follow-up was 25
      months (range, 6-39 months). The diagnoses included rheumatoid arthritis in 10
      patients, degenerative arthritis in 4, and post-traumatic arthritis in 6.
      Arthrodesis relieved pain and restored stability in all patients. Solid osseous
      union occurred in 19 patients (95%). The average interval to fusion was 8 weeks
      for DIP and 12 weeks for IP joint arthrodesis. Solid osseous union occurred in 19
      patients (95%). The average interval to fusion was 8 weeks for distal
      interphalangeal joint arthrodesis and 12 weeks for interphalangeal joint of the
      thumb. There were three complications: one delayed union, one nonunion because of
      a short screw, and one dorsal skin necrosis with amputation. It was shown that
      distal interphalangeal joint arthrodesis with a Herbert screw is a technique with
      several advantages: good clinical results, high rates of fusion, early
      mobilization, and the screw does not need to be removed after the fusion heals.
      Potential complications may be avoided by using the Herbert mini-screw.

PMID- 14577725
TI  - A previously unreported complication of the AO cannulated 4.0- and 4.5-mm screw
      systems: a review of three cases.
AB  - Cannulated screws are utilized widely in the management of periarticular
      fractures and osteotomies. Reports of complications related to these screws have
      increased as use has become more commonplace. A novel mode of mechanical failure
      of 4.0-mm and 4.5-mm A-O cannulated screws is described in three patients, as
      well as hypotheses regarding possible causes of the failure. It may be prudent to
      predrill and tap dense cortical bone when such devices are used in teenagers and
      young adults patients in an attempt to avoid similar damage to the screw during
      insertion.

PMID- 14577726
TI  - Lipoma arborescens (diffuse articular lipomatosis).
AB  - Lipoma arborescens (LA) (diffuse articular lipomatosis, synovial lipomatosis,
      Hoffa disease) is a rare intra-articular lesion of unknown etiology. This article
      presents three patients who had LA, which was diagnosed in the knee in two
      patients and in the wrist of the third patient. Details of the clinical and
      histomorphological examination and treatment, in addition to a review of the
      literature, are discussed. The article concludes that in patients with a slow
      increase in painless swelling of the joints, unresolving articular pain with or
      without limited motion, or intermittent effusions following a minor trauma, LA
      should be considered in the differential diagnosis. It should be remembered that
      LA occurs in joints other than the knee, such as the elbow, shoulder, and wrist.
      Although recommended surgery involves arthrotomy and synovectomy, arthroscopic
      synovectomy may be a useful treatment modality, particularly in the larger joints
      as the recurrence rate is low.

PMID- 14577727
TI  - Building the bridge to quality.

PMID- 14577728
TI  - Students who fail clinical courses: keeping open a future of new possibilities.

PMID- 14577729
TI  - Walking a fine line: graduate nurses' transition experiences during orientation.
AB  - A phenomenological study was conducted to investigate graduate nurses' transition
      experiences during orientation. A purposive sample of 10 graduate nurses
      participated. Ten theme clusters emerged when the formulated meanings were
      organized into categories. Graduates experienced mixed emotions as they began
      orientation. Preceptors played a key role in the transition process, affecting
      participants' thoughts and progress. Graduates quickly realized the many
      differences between work and school, and were surrounded by feelings of stress as
      they assumed the new role of RN. For some, coping with death and dying was an
      emotionally difficult experience for which they felt unprepared. Finding a rhythm
      brought graduates confidence and feelings of accomplishment, and self-reflection
      emerged as an important and integral part of the transition process. Despite the
      challenges and stress of orientation, graduates found great meaning in their
      work, and most expressed readiness to be on their own by the end of 12 weeks.

PMID- 14577730
TI  - The effectiveness of standardized patients as a teaching method for nursing
      fundamentals.
AB  - This study compared two teaching methods and examined their effects on student
      nurses' clinical competence. A nonequivalent control group was used for this
      quasi-experimental research, and a posttest design was used to compare the
      effects on clinical competence. A protocol was developed to include critical
      behaviors and was used as a checklist for evaluation. The results showed that the
      standardized patient (SP) method was more effective than the traditional method
      in helping students: * Identify patient needs. * Perform mouth care, back care,
      position change, nelaton catheterization, and glycerine enema. * Use more
      effective communication skills. The authors believe use of the SP method should
      be expanded to more areas of the fundamentals of nursing course, and its
      effectiveness and efficiency evaluated. Also, the SP method should be used to
      evaluate the clinical competence of both students and graduate nurses.

PMID- 14577731
TI  - The effect of intimate partner violence education on nurse practitioners'
      feelings of competence and ability to screen patients.
AB  - This study examined the prevalence of formal intimate partner violence (IPV)
      education during basic and advanced practice programs and its effect on the
      likelihood of screening for IPV. A national, random sample of 553 nurse
      practitioners completed a written survey documenting their IPV educational
      experiences in both their basic and advanced practice programs. Although 77.9%
      had received IPV education at some point in their nursing education, this
      education had a far greater effect on their subjective feelings of competence and
      comfort in working with IPV patients than it had on the likelihood of their
      screening or identifying IPV victims in their practice. Nurse educators must
      provide students with the words, body language, and screening measures to use to
      screen effectively. Study implications for nursing education, limitations, and
      recommendations are discussed.

PMID- 14577732
TI  - Medication errors: more basic than a system issue.
AB  - The Institute of Medicine's 2000 report drew attention to both U.S. health care
      agencies and the medication errors that occur within them. However, this
      attention focused on a more basic and fundamental issue within the medication
      error concern: nurses' mathematical skills and competence. This article describes
      a nationwide study assessing processes to validate mathematical skills for
      medication administration. Practices within educational and acute care
      institutions are explored, and recommendations for future action are noted with a
      call for 100% accuracy on all mathematical examinations for medication
      administration.

PMID- 14577733
TI  - Teaching baccalaureate nursing students to prevent medication errors using a
      problem-based learning approach.
AB  - An objective of the baccalaureate nursing curriculum at Thomas Jefferson
      University, Jefferson College of Health Professions is to facilitate nursing
      students' transfer of medication error knowledge into preventive action in the
      clinical unit. Using a problem-based learning approach, first-semester students
      are exposed to situations that reflect the real-world scope and complexity of
      medication administration and errors. Using the frameworks of Failure Mode
      Analysis and Human Error Mode and Effects Analysis, student groups identify
      hypotheses, devise solutions, and develop continuous quality improvement
      processes to prevent errors and facilitate error reporting. Problem-based
      learning is used in subsequent clinical experiences throughout the curriculum.
      This reinforcement, combined with a focus on increasingly complex pharmacological
      agents and medication calculations, enables students to employ critical thinking
      skills and develop the confidence necessary for safe, professional practice.

PMID- 14577734
TI  - Read all about it: writing health articles for the student newspaper.
AB  - The thrust of health care is prevention. Individuals are encouraged to become
      better informed about health issues and to assume more responsibility for their
      own health. Health has become a popular topic in the press, on radio and
      television, and on the Internet. Like other health care professionals, nurses are
      placing increased emphasis on health promotion and consumer education. Expanding
      the nurse educator role means oral and written communication skills are assuming
      greater importance, and nursing students need the opportunity to continuously
      develop these skills as part of their educational experience. Writing for the
      student newspaper gives students the opportunity to broaden and improve their
      writing skills and to share their expertise while promoting health.

PMID- 14577735
TI  - Teaching medication calculation for conceptual understanding.
AB  - Medication calculation ability has been identified as a common weakness among
      nursing students. However, few new methods for teaching this skill have been
      devised. This article describes the development of a teaching strategy based on a
      constructivist learning model.

PMID- 14577736
TI  - Use of videotaping to assess competencies and course outcomes.
AB  - A constant challenge in nursing education is effectively teaching competencies
      and allowing students to safely practice essential nursing skills. Faculty
      members must develop sound methods of instruction to achieve program outcomes,
      which determine program effectiveness, assure professional readiness, and meet
      accreditation standards. To this end, the use of videotaping is suggested.
      Videotaping offers a safe way for students to practice skills and develop
      confidence prior to actual performance. This article reviews the literature on
      videotaping and discusses videotaping as used at Central Missouri State
      University baccalaureate school of nursing. Videotaping is a teaching-learning
      strategy used to help students develop effective communication, physical
      assessment, and selected psychomotor skills. Videotaping also provides students
      with a mechanism for detailed instructor feedback to improve performance.

PMID- 14577737
TI  - The growing epidemic of child and youth obesity--another twist?

PMID- 14577738
TI  - Predicting change in physical activity, dietary restraint, and physique anxiety
      in adolescent girls: examining covariance in physical self-perceptions.
AB  - OBJECTIVES: To examine: i) the mean changes in adolescent females' body mass
      index (BMI), global self-esteem, physical self-perceptions, social physique
      anxiety, physical activity, and dietary restraint; ii) the stability of measuring
      self-perceptions, BMI, self-esteem, physique anxiety, activity, and dietary
      restraint; and iii) the relationships among changes in these variables over 12
      months. METHODS: 631 female adolescents (15-16 years old) involved in a two-year
      study of self-report measures completed validated questionnaires in high school
      classroom settings. RESULTS: There were small but significant group increases in
      BMI and social physique anxiety and significant decreases in sport, conditioning,
      and strength physical self-perceptions and physical activity. Stability analysis
      indicates moderate to strong stability for all variables. Change analyses
      indicated that BMI, due to its high stability, is a poor predictor of change in
      all variables. Stronger significant correlations were noted between change in
      body appearance self-perceptions and change in social physique anxiety (r=-0.54)
      and dietary restraint (r=-0.27). There was also a significant relationship
      between change in physical activity and the physical self-perceptions, although
      conditioning was the only significant (p<0.05) predictor of change in physical
      activity (beta=0.340). INTERPRETATION: Physical self-perceptions are a stronger
      predictor of change in physical activity, dietary restraint, and social physique
      anxiety compared to BMI. This demonstrates the importance of physical self
      perceptions when investigating health-related behaviours associated with dieting
      and physical activity. The decline in physical activity and increase in BMI is an
      ongoing concern, as is the link between body appearance self-perceptions and
      dietary restraint and social physique anxiety.

PMID- 14577739
TI  - A collaborative system-wide response to influenza outbreak management in
      Saskatoon Health Region.
AB  - OBJECTIVE: To describe the benefits of a regional, collaborative, system-wide
      approach to influenza outbreak management. PARTICIPANTS: Senior management
      representatives from affected parts of the Regional Health Authority. SETTING:
      Saskatoon Health Region. INTERVENTION: Public Health proactively engaged a broad
      based, multidisciplinary planning/management group to minimize the effect of the
      influenza outbreak, and institute best practice in prevention and outbreak
      management system-wide for the future. OUTCOMES: Earlier recognition and faster
      resolution of influenza outbreaks, fewer outbreaks, reduced pressure on acute
      care, greater compliance with amantadine prophylaxis, and improved immunization
      rates in seniors and health care workers. CONCLUSION: While many of these
      interventions and best practices have been recommended by individual sectors,
      when Public Health takes a system-wide approach facilitated by regionalization,
      it results in optimized planning, co-ordination, evaluation and successful
      outcomes.

PMID- 14577740
TI  - The association between influenza immunization coverage rates and hospitalization
      for community-acquired pneumonia in Alberta.
AB  - BACKGROUND: We compared regional coverage rates of influenza vaccination
      (composition in 1999/00 was A/Sydney-like A/Beijing-like B/Yamanashi-like and in
      2000/01 was A/Moscow A/New Caledonia B/Beijing) to the rates, cost, and mortality
      for community-acquired pneumonia. METHODS: We used the Pearson's correlation
      coefficient to establish linear associations between variables derived from
      Alberta administrative data during the period April 1, 1999 to March 31, 2001.
      RESULTS: The influenza vaccination coverage rate for the 17 health regions varied
      between 30% to 80% (mean 70%) in Alberta seniors (n=298,473). The annual
      hospitalization and ambulatory community-acquired pneumonia attack rates were 2%
      and 6.5% per year respectively. There were strongly negative correlations between
      vaccination coverage rates and pneumonia rates requiring hospitalization (r1999=
      0.59 and r2000=-0.79 with both p<0.05), total per capita physician and hospital
      costs for pneumonia (r1999=-0.57 and r2000=-0.79 with both p<0.01), community
      diagnosed pneumonia rate (r1999=-0.39, p=0.12 and r2000=-0.70, p<0.01) and per
      capita in-hospital mortality for pneumonia (r1999=-0.30, p=0.24 and r2000=-0.57,
      p<0.05). Per capita costs, rates, and mortality were highest and influenza
      vaccinations rate lowest in the northern, remote health regions. The per capita
      vaccination cost (about 10 dollars) was small in relationship to the per capita
      cost of hospital care for pneumonia (about 100 dollars). CONCLUSION: Regional
      under-utilization of preventive influenza vaccination in Alberta seniors is
      associated with increased utilization of health services for community-acquired
      pneumonia.

PMID- 14577741
TI  - Temporal correlation between opiate seizures in East/Southeast Asia and B.C.
      heroin deaths: a transoceanic model of heroin death risk.
AB  - BACKGROUND: Because heroin supply changes cannot be measured directly, their
      impact on populations is poorly understood. British Columbia has experienced an
      injection drug use epidemic since the 1980s that resulted in 2,590 illicit drug
      deaths from 1990-1999. Since previous work indicates heroin seizures can
      correlate with supply and B.C. receives heroin only from Southeast Asia, this
      study examined B.C. heroin deaths against opiate seizures in East/Southeast Asia.
      METHODS: Opiate seizures in East/Southeast Asia and data from two B.C. mortality
      datasets containing heroin deaths were examined. The Pearson correlation
      coefficient for seizures against each mortality dataset was determined. RESULTS:
      Opiate seizures, all illicit drug deaths and all opiate deaths concurrently
      increased twice and decreased twice from 1989-1999, and all reached new peak
      values in 1993. Three B.C. sub-regions exhibited illicit drug deaths rate trends
      concurrent with the three principal datasets studied. The Pearson correlation
      coefficient for opiate-induced deaths against opiate seizures from 1980-1999 was
      R=0.915 (p<0.0001), and for illicit drug deaths against opiate seizures from 1987
      1999 was R=0.896 (p<0.0001). CONCLUSIONS: From 1980-1999, opiate seizures in
      East/Southeast Asia were very strongly correlated with B.C. opiate and illicit
      drug deaths. The number of B.C. heroin-related deaths may be strongly linked to
      heroin supply. Enforcement services are not effective in preventing harm caused
      by heroin in B.C.; therefore, Canada should examine other methods to prevent
      harm. The case for harm reduction is strengthened by the ineffectiveness of
      enforcement and the unlikelihood of imminent eradication of heroin production in
      Southeast Asia.

PMID- 14577742
TI  - Who seeks treatment for cannabis-related problems?
AB  - PURPOSE: To examine the types of presenting problems and symptoms among
      individuals seeking treatment for cannabis-related problems in a large treatment
      centre in Ontario. METHODS: Data from assessment interviews conducted with
      clients who identified cannabis as their primary drug problem (n=426) were
      analyzed using descriptive statistics. RESULTS: The majority of people seeking
      treatments were male (80%) and single (77%). Cannabis treatment seekers varied in
      their socio-demographic characteristics, drug consumption, pressure to seek
      treatment, and adverse consequences of cannabis use. They experienced a broad
      range of substance-related problems, however, the majority were classified as
      below the action stage in terms of readiness to change their drug consumption.
      Daily users were older, more likely to be employed, to be cannabis dependent, to
      suffer from an anxiety disorder, and to use multiple substances. DISCUSSION:
      Cannabis treatment seekers are a heterogeneous group. A better understanding of
      the relationship between client characteristics and different interventions may
      improve outcomes.

PMID- 14577743
TI  - Requiring help injecting as a risk factor for HIV infection in the Vancouver
      epidemic: implications for HIV prevention.
AB  - BACKGROUND: Requiring help injecting was recently associated with syringe
      sharing, and later HIV-1 and HCV seroconversion among injection drug users (IDU)
      in Vancouver. This risk factor remains poorly understood. The present study
      investigates this risk factor among Vancouver IDUs. METHODS: We evaluated factors
      associated with requiring help injecting among participants enrolled in the
      Vancouver Injection Drug User Study (VIDUS) using univariate and logistic
      regression analyses. VIDUS participants who were followed-up during the period
      December 2000 to December 2001 were eligible for the present analyses. We also
      evaluated self-reported reasons for requiring help injecting. RESULTS: Overall,
      661 active injection drug users were interviewed during the study period. Among
      this population, 151 (22.8%) had required help injecting during the last six
      months, whereas 510 (77.2%) indicated that they had not. Variables that were
      independently associated with requiring help injecting included borrowing a used
      syringe (adjusted odds ratio [AOR] = 2.18), frequent cocaine injection (AOR =
      1.57), and female gender (AOR = 2.29). Among males, the most common reasons for
      requiring help injecting were: having no viable veins (77.1%), and anxiousness or
      being drug sick (42.9%). Among females, the most common reasons reported were:
      having no viable veins (71.6%), jugular injection or 'jugging' (45.7%), and being
      anxious or drug sick (27.2%). Almost twice as many females (13.6% vs 7.1%)
      reported not knowing how to inject as their reason for requiring help injecting.
      CONCLUSION: Although current public health approaches, such as needle exchange,
      are unable to address the concerns associated with requiring help injecting,
      available evidence suggests that safer injecting facilities have the potential to
      substantially mitigate this risk behaviour.

PMID- 14577744
TI  - 'What is Health?' campaign.

PMID- 14577745
TI  - Defining health and the physician's social responsibility.

PMID- 14577746
TI  - Emerging issues associated with HIV patients seeking advice from health food
      stores.
AB  - OBJECTIVES: To ascertain the recommendations, training and education of health
      food store employees and determine how they communicate the costs, benefits and
      risks associated with natural health products for the HIV/AIDS community.
      METHODS: Four male research assistants, posing as asymptomatic HIV-positive
      individuals, inquired of employees of all retail health food stores in a major
      Canadian city as to what is recommended for their condition. The research
      assistants asked about product costs, side effects, potential drug interactions
      and efficacy. They also inquired as to employee education related to
      Complementary and Alternative Medicine (CAM) and noted whether employees asked
      about which conventional medications they were taking and whether they
      recommended that the subjects seek physician or CAM provider advice. RESULTS: A
      total of 32 stores were included. Eight store employees (25%) offered no advice;
      eight (25%) inquired whether the subjects were currently taking medications; six
      (19%) suggested visiting a physician; and eight (25%) suggested visiting a CAM
      provider. A total of 36 different products (mean 2.3 per employee) were
      recommended with considerable variability in product evidence and cost. The
      education of the employees varied from postgraduate education (n=3), to
      undergraduate degree (n=3), college level (n=5) in CAM, or no formal education in
      CAM (n=21). CONCLUSION: There was considerable heterogeneity in advice on natural
      food products provided by employees of natural food stores and, in general, these
      individuals had limited formal training in CAM. The products they recommended had
      limited evidence supporting their efficacy and in some instances were potentially
      harmful and had considerable costs. The findings of this study support the need
      to further examine how best to regulate this growing component of the health care
      system.

PMID- 14577747
TI  - Estimation of the misclassification rate of self-reported visual disability.
AB  - PURPOSE: To estimate the misclassification rate of self-reported visual
      disabilities in a hospital-based population with known visual impairment.
      METHODS: Subjects (N=570) were recruited among patients aged 50 years and more
      and classified to three categories of visual impairment level. The questionnaire
      was administered to consenting patients through a telephone interview. Data
      collected from questionnaires and medical records were compared regarding
      severity of visual impairment. Sensitivity and specificity were determined for
      each question. Predictive ability and misclassification rates were computed for
      various prevalences. RESULTS: Questions related to near and far distance visual
      acuity with glasses have both a good sensitivity (82.6% and 81.8%) and a good
      specificity (85.6% and 88.9%) for the presence of severe visual impairment.
      CONCLUSION: The findings allow the determination of the misclassification rate
      and predictive ability. This could be useful to estimate the prevalence of visual
      impairment from health surveys.

PMID- 14577748
TI  - Respiratory symptoms and exposure to wood smoke in an isolated northern
      community.
AB  - BACKGROUND: Wood smoke has been associated with respiratory symptoms. This study
      examined the prevalence of respiratory symptoms and health effects of wood smoke
      exposures (from home heating, curing meat, and tanning hides) among residents of
      Deline, Northwest Territories (NWT). METHODS: A survey was conducted of all
      residents. Relationships between wood smoke and respiratory symptoms were
      examined. RESULTS: The response rate was 70.2% (n=402). 71% of people at least 18
      years old were current smokers. Prevalence of symptoms was higher for women (odds
      ratios (ORs) 1.3-3.1). Women who smoked were more likely to be exposed to indoor
      smoke from curing and tanning. ORs for respiratory symptoms were higher for
      females, increased with age, and were strongly affected by smoking. Among those
      at least 18 years old, phlegm on winter mornings (6.5 (95% CI: 2.3-18.1)),
      dyspnoea (5.1 (95% CI: 1.9-13.2)), and watery or itchy eyes (3.6 (95% CI: 1.4
      9.0)) were significantly related to self-reported outdoor wood smoke and smoke
      curing. Home heating was marginally associated with wheeze. No significant
      associations were found for males. CONCLUSIONS: Women engaged in curing/tanning
      demonstrated increased prevalence of respiratory symptoms. The cultural
      importance of these activities precludes abandoning them. Smoking cessation,
      limiting wood smoke exposure times, and process modifications in curing and
      tanning could reduce risk of adverse health effects.

PMID- 14577749
TI  - Method for ascertaining denominators for evaluation of population coverage with
      pneumococcal vaccine.
AB  - BACKGROUND: Immunization programs may collect numerator data for the estimation
      of pneumococcal vaccine coverage, but program evaluators do not have appropriate
      denominator data for estimation of pneumococcal vaccine coverage, particularly
      among those eligible for vaccine on the grounds of having chronic health
      conditions. METHODS: We partitioned the Alberta population into 6 mutually
      exclusive groups, all but one of which met Canadian recommendations for
      pneumococcal vaccination. Age-sex specific prevalence rates for each group were
      estimated using data on chronic health conditions from the Alberta over-sample of
      the 1996 Household component of the National Population Health Survey, from
      Alberta Health and Wellness rosters of nursing home residents, and from the
      Alberta Health Care Insurance Plan Stakeholder Registry. We applied these to
      Alberta Population Projections to estimate the numbers of persons who should be
      vaccinated. RESULTS: The proportion of persons recommended for vaccination on the
      grounds of chronic health condition ranged from 1.5% among those aged less than
      12 years to 36% among persons aged 80 years or older. The total number of persons
      recommended for vaccination at mid-year 2000 is estimated to be 638,561 (21.5% of
      the Alberta population). INTERPRETATION: This methodology provides denominators
      for the estimation of pneumococcal vaccine coverage and permits monitoring of
      local and regional progress towards national goals.

PMID- 14577750
TI  - How are new refugees doing in Canada? Comparison of the health and settlement of
      the Kosovars and Czech Roma.
AB  - BACKGROUND: In 1999, a group of Kosovars arrived in Hamilton, Ontario, with a
      coordinated international pre-migration plan, as part of the United Nations
      Humanitarian Evacuation Program. Since 1997, a substantial number of Roma
      refugees from the Czech Republic also arrived in Hamilton, with no special pre
      migration planning. This study examined whether the organized settlement efforts
      led to better adaptation and perceived health for the Kosovars, using the Czech
      Roma as a comparison group. METHODS: Adult members of 50 Kosovar (n=157
      individuals) and 50 Czech Roma (n=76 individuals) randomly selected families
      completed a questionnaire on sociodemographics, health, well-being, and perceived
      adaptation to Canada. Differences between groups were examined using univariate
      and multivariate analyses. Comparison was made to the Ontario population where
      possible. RESULTS: There were more Kosovars than Czech Roma over the age of 50
      (22.1% vs 10.5%, p=0.03). Nearly one quarter (21.7%) of the Kosovars had a score
      indicating post-traumatic stress disorder (PTSD) on the Harvard Trauma
      Questionnaire (HTQ), compared to none of the Roma (p<0.001). After adjustment for
      age and PTSD, the Kosovars were significantly more likely to report fair or poor
      adaptation to Canada (OR=10.5, 95% CI=3.6-31.2) and that life is somewhat or very
      stressful (OR=3.9, 95% CI=2.1-7.4). Differences for other measures were no longer
      significant after adjustment. CONCLUSIONS: The health and adaptation of the
      Kosovars was not better than that of the Czech Roma. Reasons for this finding may
      include differences in demographics, the presence of PTSD, and differing length
      of time since arrival in Canada.

PMID- 14577751
TI  - Vitamin A concentration in umbilical cord blood of infants from three separate
      regions of the province of Quebec (Canada).
AB  - BACKGROUND: Inuit women from Northern Quebec have been shown to consume
      inadequate quantities of vitamin A. This study was conducted to evaluate the
      prevalence of blood vitamin A deficiency in newborns from 3 distinct populations
      of the province of Quebec. METHODS: 594 newborns were included in this study (375
      Inuit newborns from northern Quebec (Nunavik), 107 Caucasian and Native newborns
      from the Lower Northern Shore of the Saint-Lawrence River (LNS) and 112 newborns
      from Southern Quebec where clinical vitamin A deficiency is uncommon). Mothers
      were recruited at delivery and vitamin A (retinol) was analyzed from umbilical
      cord blood samples by reversed-phase high-pressure liquid chromatography.
      RESULTS: Nunavik and LNS newborns had significantly lower mean vitamin A
      concentrations in cord blood compared to Southern Quebec participants (15.7
      microg/dL, 16.8 microg/dL and 20.4 microg/dL respectively). The differences
      observed were similar when adjusted for sex and birthweight. Results also showed
      that 8.5% of Nunavik newborns and 12.2% of LNS newborns were below 10.0
      microg/dL, a level thought to be indicative of blood vitamin A deficiency in
      neonates. CONCLUSION: These data suggest that a carefully planned vitamin A
      supplementation program during pregnancy in Nunavik and LNS might be indicated to
      promote healthy infant development.

PMID- 14577752
TI  - Accountability in public health units: using a modified nominal group technique
      to develop a balanced scorecard for performance measurement.
AB  - BACKGROUND: Little attention has been paid to the need for accountability
      instruments applicable across all health units in the public health system. One
      tool, the balanced scorecard was created for industry and has been successfully
      adapted for use in Ontario hospitals. It consists of 4 quadrants: financial
      performance, outcomes, customer satisfaction and organizational development. The
      aim of the present study was to determine if a modified nominal group technique
      could be used to reach consensus among public health unit staff and public health
      specialists in Ontario about the components of a balanced scorecard for public
      health units. METHODS: A modified nominal group technique consensus method was
      used with the public health unit staff in 6 Eastern Ontario health units (n=65)
      and public health specialists (n=18). RESULTS: 73.8% of the public health unit
      personnel from all six health units in the eastern Ontario region participated in
      the survey of potential indicators. A total of 74 indicators were identified in
      each of the 4 quadrants: program performance (n=44); financial performance
      (n=11); public perceptions (n=11); and organizational performance (n=8).
      INTERPRETATION: The modified nominal group technique was a successful method of
      incorporating the views of public health personnel and specialists in the
      development of a balanced scorecard for public health.

PMID- 14577753
TI  - A novel three-dimensional network constructed from tetramolybdate clusters linked
      via two types of copper complex fragments: synthesis, characterization, and
      magnetic behavior of [[CuII(2,2'-bpy)][CuII(IN)2][Mo4O12(OH)2]].
AB  - A novel three-dimensional copper molybdate with mixed ligands, [[Cu(II)(2,2'
      bpy)][Cu(II)(IN)(2)][Mo(4)O(12)(OH)(2)]] (IN(-) = isonicotinate ion, 2,2'-bpy =
      2,2'-bipyridine), 1, has been hydrothermally synthesized and structurally
      characterized, and this compound is built from an unprecedented tetranuclear
      molybdenum oxide cluster covalently bonded to two types of copper complex
      fragments, [Cu(II)(2,2'-bpy)](2+) and [Cu(II)(IN)(2)], via terminal oxygen atoms
      of [MoO(6)] octahedra. Crystal data for compound 1: monoclinic, space group C2/c,
      a = 16.4755 A, b = 10.3714 A, c = 17.4382 A, alpha = 90.0000 degrees, beta =
      94.8098 degrees, gamma = 90.0000 degrees; V = 2969.24 A(3); Z = 2. Variable
      temperature magnetic susceptibility indicates that both ferromagnetic and
      antiferromagnetic interactions exist in 1.

PMID- 14577754
TI  - Copper(I) pseudorotaxane monolayers assembled on gold electrodes.
AB  - Two new copper (I) pseudorotaxanes bearing a thioctic acid appended unit have
      been prepared and deposited onto a gold electrode surface, leading to surface
      attached electroactive pseudorotaxanes.

PMID- 14577755
TI  - A novel one-dimensional cyano-bridged Ni3Fe2 ferromagnet constructed from
      bimetallic molecular squares.
AB  - Reaction of the complex [Ni(rac-CTH)](2+) (rac-CTH = rac-5,7,7,12,14,14
      hexamethyl-1,4,8,11-tetraazacyclotetradecane) with [Fe(CN)(6)](3-) leads to a
      novel cyano-bridged Ni(3)Fe(2) complex, [[Ni(rac-CTH)](3)[Fe(CN)(6)](2)](4). The
      structure consists of an alternating arrangement of [Fe(CN)(6)Ni(rac-CTH)](2)
      squares and trans-planar [Ni(rac-CTH)](2+) units bridged by cyanide groups to
      give a neutral 1D chain running along the a axis. Magnetic measurements reveal
      the occurrence of ferromagnetic coupling between Fe(III) and Ni(II) ions and 3D
      magnetic ordering at 3 K due to interchain interactions. Canting of the moments
      is inferred from the low value of the magnetization of the saturation below T(c).

PMID- 14577756
TI  - Ferromagnetism in a dinuclear nickel(II) complex containing triethylenetetramine
      and tricyanomethanide.
AB  - Triethylenetetramine (L(4)) was used as a tetradentate blocking ligand that,
      after complexation with Ni(II), leaves two sites ready for ligation with
      tricyanomethanide. The formed binuclear complex
      [L(4)Ni(NCC(CN)CN)(2)NiL(4)](ClO(4))(2) exhibits a ferromagnetic coupling with
      J/hc = +0.15 cm(-1) and g(Ni) = 2.126; below 16 K, a ferromagnetic ordering is
      evidenced by ac magnetic susceptibility (both in-phase and out-of-phase),
      magnetization, field-cooled magnetization, and zero-field-cooled magnetization
      measurements.

PMID- 14577757
TI  - Copper hydroperoxo species activated by hydrogen-bonding interaction with its
      distal oxygen.
AB  - A novel copper(II)[bond]OOH complex with functional ligand that can form a
      hydrogen bond with the distal oxygen of hydroperoxide has been designed and
      prepared as a structural/functional model of dopamine beta-hydroxylases, whose
      spectroscopic characterization and decomposition rates have indicated that the
      hydroperoxide is activated through the hydrogen-bonding interaction with the
      distal oxygen.

PMID- 14577758
TI  - New routes to high nuclearity clusters: fluoride-based octametallic and
      tridecametallic clusters of manganese.
AB  - The reaction of MnF(3) with 5,6-dimethylbenzotriazole (Me(2)BTAH) gives the
      [Mn(III)(8)] complex [Mn(8)O(4)(OMe)(2)(Me(2)BTA)(6)F(8)(Me(2)BTAH)(MeOH)(8)] and
      the [Mn(IV)(3)Mn(III)(10)] complex
      [Mn(13)O(12)(Me(2)BTA)(12)F(6)(MeOH)(10)(H(2)O)(2)]. The octametallic species is
      an "intermediate" in the formation of the tridecametallic cluster.

PMID- 14577759
TI  - [Na(THF)2Cr(N3N)]: The first trigonal monopyramidal chromium(II) complex.
AB  - Reduction of [Cr(N(3)N)] (1) [(N(3)N)(3)(-) = ((SiMe(3)NCH(2)CH(2))(3)N)(3)(-)]
      with sodium powder in THF affords the yellow, extremely air-sensitive
      amidochromate(II) [Na(THF)(2)Cr(N(3)N)] (2) in good yield. Complex 2 has an
      effective magnetic moment of 5.1 mu(B) indicative of a d(4) high-spin electronic
      configuration. (1)H NMR spectroscopy in solution and single-crystal X-ray
      crystallography show that compound 2 is composed of idealized C(s) symmetric
      contact ion pairs, in which trigonal-monopyramidal [Cr(II)(N(3)N)](-) anions are
      linked to the [Na(THF)(2)](+) countercations by two bridging amide ligands. DFT
      calculations of 1, 2, and the anion [Cr(N(3)N)](-) at the RI-BP86/TZVPP level of
      theory provide in combination with extended Huckel calculations a rationale for
      the observed structural changes from 1 to 2.

PMID- 14577760
TI  - Photoluminescent dinuclear lanthanide complexes with tris(2-pyridyl)carbinol
      acting as a new tetradentate bridging ligand.
AB  - A tripodal ligand, tris(2-pyridyl)carbinol, affords a novel tetradentate
      coordination mode in homodinuclear lanthanide complexes, which exhibit remarkably
      short distances between metal ions. The strong luminescences of Eu(III) and
      Tb(III) complexes with the ligand demonstrate that the ligand has a suitable
      excited state for energy transfer from the ligand to the Eu(III) and Tb(III)
      centers, respectively.

PMID- 14577761
TI  - (NaLa2)NaPtO6: The first 2H-perovskite related oxide with a rare earth cation on
      the A-site.
AB  - Crystals of (NaLa(2))NaPtO(6) were grown in an acidic ("wet") NaOH flux.
      (NaLa(2))NaPtO(6) forms in a 2H-perovskite related structure type and contains
      mixed cation (Na/La) occupancy on the A-site. The crystal was a rhombohedral
      obverse-reverse twin, and it crystallizes in the space group R3c (hexagonal
      setting) with lattice parameters of a = 9.5031(2) A and c = 11.4625(5) A.
      (NaLa(2))NaPtO(6) is the first example of an m = 0, n = 1 (A(3)A'BO(6)) member of
      the A(3n)+3m)A'(n)B(3m+n)O(9m+6n) family of oxides where either a lanthanide or a
      sodium cation occupies the A-site.

PMID- 14577762
TI  - Nanoparticles of Prussian blue ferritin: a new route for obtaining nanomaterials.
AB  - The dissociation of apoferritin into subunits at pH 2 followed by its re
      formation at pH 8.5 in the presence of hexacyanoferrate(III) gave rise to a
      solution containing hexacyanoferrate(III) trapped within the apoferritin and
      hexacyanoferrate(III) outside it. The addition of Fe(II) to the dialyzed solution
      resulted in the appearance of the characteristic Prussian blue color. The UV-vis
      spectrum of this solution showed a broad band centered at 710 nm, and the IR
      spectrum contained a broad-medium band at 2083 cm(-1). Both features are
      consistent with the charge-transfer band and the C[bond]N stretching mode in the
      Fe(II)[bond]CN[bond]Fe(III) fragment of PB. TEM images of the obtained Prussian
      blue solution showed discrete spherical electron dense iron particles with an
      average size of about 5 nm. This represents a new route for preparing metallic
      nanoparticles that offers control over the size and protection against
      aggregation. Moreover, the fact that the particles are obtained by reaction of
      hexacyanoferrate(III) and iron(II) building blocks opens up the possibility of
      obtaining not only homo- but also heterobimetallic nanoparticles.

PMID- 14577763
TI  - Density functional calculations on the binding of dinitrogen to the FeFe cofactor
      in Fe-only nitrogenase: FeFeco(mu 6-N2) as intermediate in nitrogen fixation.
AB  - The geometries and stabilities of the FeFe cofactor at different oxidation states
      and its complexes with N(2) have been determined by density functional
      calculations. These calculations support an EPR-inactive resting state of the
      FeFe cofactor with four Fe(2+) and four Fe(3+) sites (4Fe(2+)4Fe(3+)).
      FeFeco(mu(6)-N(2)) with a central dinitrogen ligand is predicted to be the most
      stable complex of the FeFe cofactor with N(2). It is easily formed by penetration
      of N(2) into the trigonal Fe(6) prism of the FeFe cofactor with an approximate
      barrier of 4 kcal mol(-1). The present DFT results suggest that an FeFeco(mu(6)
      N(2)) entity is a plausible intermediate in dinitrogen fixation by nitrogenase.
      CO is calculated to bind even more strongly than N(2) to the FeFe cofactor so
      that CO may inhibit the reduction of nitrogen by Fe-only nitrogenase.

PMID- 14577764
TI  - Exploration of composition space in templated uranium sulfates.
AB  - The phase stability of organically templated uranium sulfates in the
      [UO(2)(CH(3)CO(2))(2).2H(2)O/homopiperazine/H(2)SO(4)] and
      [UO(2)(CH(3)CO(2))(2).2H(2)O/N,N-dimethylethylenediamine/H(2)SO(4)] systems has
      been studied using composition space. Two new compounds were formed in each
      system; [N(2)C(5)H(14)](2)[UO(2)(SO(4))(3)] (USO-17) and
      [N(2)C(5)H(14)][UO(2)(H(2)O)(SO(4))(2)] (USO-18) contain homopiperazine, and
      [N(2)C(4)H(14)][UO(2)(SO(4))(2)] (USO-19) and
      [N(2)C(4)H(14)][(UO(2))(2)(H(2)O)(SO(4))(3)].H(2)O (USO-20) contain N,N
      dimethylethylenediamine. The relative stability of the products from each system
      is dependent upon the reactant mole fractions in the initial reaction gel.
      Crystal data: USO-17, a = 14.4975(3) A, b = 11.9109(3) A, c = 13.0157(3) A, beta
      = 110.475(1) degrees, monoclinic, C2/c (No. 15), Z = 4; for USO-18, a = 7.6955(2)
      A, b = 11.7717(3) A, c = 14.7038(4) A, orthorhombic, P22(1)2(1) (No. 18), Z = 4;
      for USO-19, a = 9.3322(1) A, b = 9.7743(2) A, c = 13.8897(3) A, orthorhombic,
      P2(1)2(1)2(1) (No. 19), Z = 4; and for USO-20, a = 11.2460(2) A, b = 10.5387(2)
      A, c = 17.0432(3) A, beta = 92.9884(6) degrees, monoclinic, P2(1)/c (No. 14), Z =
      4.

PMID- 14577765
TI  - 77Se and 87Rb Solid state NMR study of the structure of Rb2[Pd(Se4)2].Se8.
AB  - The structure of Rb(2)[Pd(Se(4))(2)].Se(8) has been investigated using (87)Rb
      magic angle spinning and static NMR and (77)Se magic angle spinning NMR. The
      number and the integrated intensities of the (87)Rb and (77)Se resonances are in
      full agreement with the crystallographic structure of the compound. The (87)Rb
      and (77)Se nuclear spin interaction parameters have been used to characterize the
      main structural units of the compound: infinite [Rb(Se(8))](x)(x+) columns and
      polymeric [Pd(Se(4))(2)](x)(2x-) sheet anions.

PMID- 14577766
TI  - A new family of spin crossover complexes with a tripod ligand containing three
      imidazoles: synthesis, characterization, and magnetic properties of
      [FeIIH3LMe](NO3)2.1.5H2O, [FeIIILMe].3.5H2O, [FeIIH3LMe][FeIILMe]NO3, and
      [FeIIH3LMe][FeIIILMe](NO3)2 (H3LMe) = Tris[2-(((2-methylimidazol-4
      yl)methylidene)amino)ethyl]amine).
AB  - A new family of spin crossover complexes, [Fe(II)H(3)L(Me)](NO(3))(2).1.5H(2)O
      (1), [Fe(III)L(Me)].3.5H(2)O (2), [Fe(II)H(3)L(Me)][Fe(II)L(Me)]NO(3) (3), and
      [Fe(II)H(3)L(Me)][Fe(III)L(Me)](NO(3))(2) (4), has been synthesized and
      characterized, where H(3)L(Me) denotes a hexadentate N(6) tripod ligand
      containing three imidazole groups, tris[2-(((2-methylimidazol-4
      yl)methylidene)amino)ethyl]amine. It was found that the spin and oxidation states
      of the iron complexes with this tripod ligand are tuned by the degree of
      deprotonation of the imidazole groups and by the 2-methyl imidazole substituent.
      Magnetic susceptibility and Mossbauer studies revealed that 1 is an HS-Fe(II)
      complex, 2 exhibits a spin equilibrium between HS and LS-Fe(III), 3 exhibits a
      two-step spin transition, where the component [Fe(II)L(Me)](-) with the
      deprotonated ligand participates in the spin transition process in the higher
      temperature range and the component [Fe(II)H(3)L(Me)](2+) with the neutral ligand
      participates in the spin transition process in the lower temperature range, and 4
      exhibits spin transition of both the Fe(II) and Fe(III) sites. The crystal
      structure of 3 consists of homochiral extended 2D puckered sheets, in which the
      capped tripodlike components [Fe(II)H(3)L(Me)](2+) and [Fe(II)L(Me)](-) are
      alternately arrayed in an up-and-down mode and are linked by the imidazole
      imidazolate hydrogen bonds. Furthermore, the adjacent 2D homochiral sheets are
      stacked in the crystal lattice yielding a conglomerate as confirmed by the
      enantiomeric circular dichorism spectra. Compounds 3 and 4 showed the LIESST
      (light induced excited spin state trapping) and reverse-LIESST effects upon
      irradiation with green and red light, respectively.

PMID- 14577767
TI  - Proof of innocence for the quintessential noninnocent ligand TCNQ in its
      tetranuclear complex with four [fac-Re(CO)3(bpy)]+ groups: unusually different
      reactivity of the TCNX ligands (TCNX = TCNE, TCNQ, TCNB).
AB  - The reactions of [fac-Re(CO)(3)(bpy)(MeOH)](PF(6)), bpy = 2.2'-bipyridine, with
      the TCNX ligands (TCNE = tetracyanoethene, TCNQ = 7,7,8,8-tetracyano-p
      quinodimethane, and TCNB = 1,2,4,5-tetracyanobenzene) in CH(2)Cl(2) gave very
      different results. No reaction was observed with TCNB whereas TCNE produced very
      labile intermediates which converted under mild conditions to structurally
      characterized [(mu-CN)[fac-Re(CO)(3)(bpy)](2)](PF(6)) with an eclipsed
      conformation relative to the almost linear Re-CN-Re axis (Re-N(NC) 2.134(8) A, Re
      C(CN) 2.098(8) A). With TCNQ, a stable tetranuclear complex [(mu(4)
      TCNQ)[Re(CO)(3)(bpy)](4)](BF(4))(4) was obtained. Its structural,
      electrochemical, and spectroscopic analysis indicates only negligible charge
      transfer from the rhenium(I) centers to the extremely strong pi acceptor TCNQ.
      Evidence includes a calculated charge of only -0.09 for coordinated TCNQ
      according to the empirical structure/charge correlation of Kistenmacher, a high
      energy nitrile stretching band nu(CN) = 2235 cm(-1), and unprecedented large
      anodic shifts >0.7 V of the reduction potentials. DFT calculations were used to
      confirm and explain the absence of electron delocalization from the electron-rich
      metals to the TCNQ acceptor bridge. Correspondingly, the X-band and high
      frequency (285 GHz) EPR data (g = 2.007) as well as the IR and UV-vis-NIR
      spectroelectrochemical results (marginal nu(CO) shifts, TCNQ(*-) chromophore
      bands) support the almost exclusive confinement of the added electron in [(mu(4)
      TCNQ)[Re(CO)(3)(bpy)](4)](3+) to the TCNQ bridge.

PMID- 14577769
TI  - Novel acetate binding modes in [Na2Cu(CH3COO)4(H2O)].H2O.
AB  - A new copper(II) acetate, [Na(2)Cu(CH(3)COO)(4)(H(2)O)].H(2)O (1), has been
      crystallized from an aqueous solution containing sodium acetate and copper(II)
      acetate monohydrate in a 4:1 ratio and the structure determined by X-ray
      crystallography. 1 crystallizes in the monoclinic space group P2(1)/c, with a =
      16.638(3) A, b = 11.781(2) A, c = 15.668(3) A, beta = 90.11(3) degrees, V =
      3071.0(11) A(3), and Z = 4. In the asymmetric unit, sodium ions bridge two
      crystallographically unique square planar [Cu(CH(3)COO)(4)](2-) units to their
      symmetry-generated neighbors to form corrugated 2D sheets of
      Na(2)Cu(CH(3)COO)(4), which are held together by H-bonding interactions involving
      the waters of crystallization. In contrast, the structures of known sodium copper
      acetates are better described as 3D frameworks. The metal centers are bridged by
      a number of acetates in novel coordination modes. The square planar Cu(II)
      geometry generated by oxygen atoms from four different acetates is an unexpected
      feature given the weak ligand field provided by the acetate ligands.

PMID- 14577768
TI  - A solid-state spectral effect in eclipsed tetracyanonickelates: X-ray crystal
      structure, polarized specular reflectance spectroscopy, and ZINDO modeling of
      Sr[Ni(CN)4].5H2O, Rb2[Ni(CN)4].H2O, and Na2[Ni(CN)4].3H2O.
AB  - Crystal structures of three Ni(CN)(4)(2)(-) salts all with eclipsed ligands and
      varying axial stacking arrangements are presented. The absorption spectra of all
      three salts show a slight red shift in the x,y-polarizations and a large red
      shift in their z-polarizations upon crystallization from solution. Semiempirical
      ZINDO calculations provide a good model of the solid state, even with only a
      three-molecule segment, allowing reproduction of the red-shifting and intensity
      increase upon crystallization found experimentally. The modified nickel beta(s,p)
      bonding parameter of -5 found appropriate for Ni coordination in our previous
      studies of single Ni(CN)(4)(2-) planes and a helically stacked
      Cs(2)[Ni(CN)(4)].H(2)O crystal was changed to -3 for the more parallel-stacked
      Ni(CN)(4)(2-) planes in this case, while beta(d) was retained at -41. Crystal
      data are as follows: Na(2)[Ni(CN)(4)].3H(2)O, triclinic space group P1, a =
      7.2980(10) A, b = 8.8620(10) A, c = 15.132(2) A, alpha = 89.311(5) degrees, beta
      = 87.326(5) degrees, gamma = 83.772(6) degrees, V = 971.8(2) A(3), T = 100 K, Z =
      4, R = 0.024, R(w) = 0.064; Sr[Ni(CN)(4)].5H(2)O, monoclinic space group C2/m, a
      = 10.356(2) A, b = 15.272(3) A, c = 7.1331(10) A, beta = 98.548(12) degrees, V =
      1115.6(3) A(3), T = 100 K, Z = 4, R = 0.024, R(w) = 0.059;
      Rb(2)[Ni(CN)(4)].1.05H(2)O, triclinic space group P1, a = 8.6020(10) A, b =
      9.6930(10) A, c = 12.006(2) A, alpha = 92.621(6) degrees, beta = 94.263(6)
      degrees, gamma = 111.795(10) degrees, V = 924.0(2) A(3), T = 100 K, Z = 4, R =
      0.034, R(w) = 0.067.

PMID- 14577770
TI  - Topological evolution in uranyl dicarboxylates: synthesis and structures of one
      dimensional UO2(C6H8O4)(H2O)2 and three-dimensional UO2(C6H8O4).
AB  - Two novel uranyl adipates are reported as synthesized via hydrothermal treatment
      of uranium oxynitrate and adipic acid. One-dimensional
      UO(2)(C(6)H(8)O(4))(H(2)O)(2) (1) [a = 9.6306(6) A, c = 11.8125(10) A,
      tetragonal, P4(3)2(1)2 (No. 96), Z = 4] consists of chains of
      (UO(2))O(4)(H(2)O)(2) hexagonal bipyramids tethered through a linear adipic acid
      backbone. Three-dimensional UO(2)(C(6)H(8)O(4)) (2) [a = 5.5835(12) A, b =
      8.791(2) A, c = 9.2976(17) A, alpha = 87.769(9) degrees, beta = 78.957(8)
      degrees, gamma = 81.365(11) degrees, triclinic, P1 (No. 2), Z = 2] is produced by
      decreasing the hydration level of the reaction conditions. This structure
      contains a previously unreported [(UO(2))(2)O(8)] building unit cross-linked into
      a neutral metal-organic framework topology with vacant channels.

PMID- 14577771
TI  - Cobalt phosphonates: an unusual polymeric cobalt phosphonate containing a
      clathrated phosphonate anion and a layered bisphosphonate.
AB  - Novel cobalt phosphonates [Co(H(2)O)(4)(H(4)L)][H(2)L].2H(2)O, 1, and
      Co(2)(H(2)O)(2)(L), 2, have been synthesized from 1,8-octylenediphosphonic acid
      (H(4)L). 1 has been fully characterized by X-ray single-crystal data, TGA, IR
      spectroscopy, and chemical analysis. The compound crystallizes in the triclinic
      space group P1 with a = 5.5415(8) A, b = 8.6382(8) A, c = 16.794 (2) A, alpha =
      87.694(2) degrees, beta = 80.859(2) degrees, gamma = 76.005(2) degrees, V =
      770.11(19) A(3), and Z = 1. A cobalt atom lies in the center of symmetry and is
      octahedrally coordinated by two oxygen atoms from two undissociated diphosphonic
      ligands H(4)L and four molecules of water. The cobalt atom and undissociated
      ligand H(4)L are combined to form polymeric chains along the c-axis, resulting in
      the formation of a one-dimensional framework. The positive charge on the cobalt
      atom remains upon coordination and is balanced by a negatively charged
      uncoordinated ligand (H(2)L) found as a clathrate in the lattice. Two lattice
      water molecules, hydrogen-bonded with the coordinated and uncoordinated ligands,
      complete the structure. The metal phosphonate chains are held together and bridge
      the uncoordinated anionic ligands by a number of strong hydrogen bonds, which
      make the structure possible. Cobalt phosphonate 2 has been characterized by TGA
      measurements, IR spectroscopy, and chemical analysis. The compound has a layered
      structure with an interlayer spacing of 14.26 A. Metal phosphonate layers are
      cross-linked by hydrocarbon chains. The water molecules are coordinated to the
      metal atom. According to IR data, compound 2 contains two equivalent PO bonds and
      one different PO bond, which may be a result of the different types of Co-O-P
      connectivity within one phosphonic group.

PMID- 14577772
TI  - Crystal structures and magnetic properties of two octacyanotungstate(IV) and (V)
      cobalt(II) three-dimensional bimetallic frameworks.
AB  - The synthesis, X-ray structures, and magnetic behavior of two new, three
      dimensional compounds [W(IV)[(mu-CN)(4)Co(II)(H(2)O)(2)](2).4H(2)O](n) (1) and
      [[W(V)(CN)(2)](2)[(mu-CN)(4)Co(II)(H(2)O)(2)](3).4H(2)O](n) (2) are presented.
      Compound 1 crystallizes in the tetragonal system, space group I4/m with cell
      constants a = b = 11.710(3) A, c = 13.003(2) A, and Z = 4, whereas 2 crystallizes
      in the orthorhombic system, space group Cmca with cell constants a = 13.543(5) A,
      b = 16.054(6) A, c = 15.6301(9) A, and Z = 4. The structure of 1 shows
      alternating eight-coordinated W(IV) and six-coordinated Co(II) ions bridged by
      single cyanides in a three-dimensional network. The geometry of each
      [W(IV)(CN)(8)](4-) entity in 1 is close to a square antiprism. Its eight cyanide
      groups are coordinated to Co(II) ions which have two coordinated water molecules
      in trans position. The structure of 2 consists of alternating eight-coordinated
      W(V) and six-coordinated Co(II) ions linked by single cyanide bridges in a three
      dimensional network. Each [W(V)(CN)(8)](3-) unit shows a geometry close to a
      square antiprism. Only six of its eight cyanide groups are coordinated to Co(II)
      ions while the other two are terminal. The Co(II) ion in 2 has the same
      CoN(4)O(2) environment as in 1. The magnetic behavior of 1 is that of
      magnetically isolated high spin Co(II) ions (S(Co) = 3/2), bridged by the
      diamagnetic [W(IV)(CN)(8)](3-) units (S(W(IV)) = 0). The magnetic behavior of 2,
      where the high spin Co(II) ions are bridged by the paramagnetic [W(V)(CN)(8)](3-)
      units [S(W(V)) = 1/2], is that of ferromagnetically coupled Co(II) and W(V)
      giving rise to an ordered ferromagnetic phase below 18 K. The magnetic properties
      of 1 are used as a blank to extract the parameters that are useful to analyze the
      magnetic data of compound 2.

PMID- 14577773
TI  - The structure of magnesium alanate.
AB  - Mg(AlH(4))(2) was produced as a nanocrystalline powder by metathesis of NaAlH(4)
      and MgCl(2). Starting with a structure estimation which was developed from an
      evaluation of FTIR data and comparison of structural properties of two solvent
      adducts, quantum chemical calculations were performed on the density functional
      theory (DFT) level. The calculated atomic positions were used to simulate an X
      ray powder diffraction pattern, based on a trigonal unit cell. The simulated
      pattern was congruent to experimental data. Thus, magnesium alanate exhibits a
      CdI(2) layer structure, the layers being formed by Mg atoms occupying the Cd
      sites and AlH(4) tedrahedra occupying the sites of the iodine atoms in CdI(2).

PMID- 14577774
TI  - Heptanuclear and decanuclear manganese complexes with the anion of 2
      hydroxymethylpyridine.
AB  - The synthesis and magnetic properties are reported of two new clusters
      [Mn(10)O(4)(OH)(2)(O(2)CMe)(8)(hmp)(8)](ClO(4))(4) (1) and
      [Mn(7)(OH)(3)(hmp)(9)Cl(3)](Cl)(ClO(4)) (2). Complex 1 was prepared by treatment
      of [Mn(3)O(O(2)CMe)(6)(py)(3)](ClO(4)) with 2-(hydroxymethyl)pyridine (hmpH) in
      CH(2)Cl(2), whereas 2 was obtained from the reaction of MnCl(2).4H(2)O, hmpH, and
      NBu(n)(4)MnO(4) in MeCN followed by recrystallization in the presence of
      NBu(n)(4)ClO(4). Complex 1.2py.10CH(2)Cl(2).2H(2)O crystallizes in the triclinic
      space group P1. The cation consists of 10 Mn(III) ions, 8 mu(3)-O(2)(-) ions, 2
      mu(3)-OH(-) ions, 8 bridging acetates, and 8 bridging and chelating hmp(-)
      ligands. The hmp(-) ligands bridge through their O atoms in two ways: two with
      mu(3)-O atoms and six with mu(2)-O atoms. Complex 2.3CH(2)Cl(2).H(2)O
      crystallizes in the triclinic space group P1. The cation consists of four Mn(II)
      and three Mn(III) ions, arranged as a Mn(6) hexagon of alternating Mn(II) and
      Mn(III) ions surrounding a central Mn(II) ion. The remaining ligation is by three
      mu(3)-OH(-) ions, three terminal chloride ions, and nine bridging and chelating
      hmp(-) ligands. Six hmp(-) ligands contain mu(2)-O atoms and three contain mu(3)
      O atoms. The Cl(-) anion is hydrogen-bonded to the three mu(3)-OH(-) ions.
      Variable-temperature direct current (dc) magnetic susceptibility data were
      collected for complex 1 in the 5.00-300 K range in a 5 kG applied field. The
      chi(M)T value gradually decreases from 17.87 cm(3) mol(-1) K at 300 K to 1.14
      cm(3) mol(-1) K at 5.00 K, indicating an S = 0 ground state. The ground-state
      spin of complex 2 was established by magnetization measurements in the 0.5-3.0 T
      and 1.80-4.00 K ranges. Fitting of the data by matrix diagonalization,
      incorporating only axial anisotropy (DS(z)(2)), gave equally good fits with S =
      10, g = 2.13, D = -0.14 cm(-1) and S = 11, g = 1.94, D = -0.11 cm(-1).
      Magnetization versus dc field scans down to 0.04 K reveal no hysteresis
      attributable to single-molecule magnetism behavior, only weak intermolecular
      interactions.

PMID- 14577775
TI  - PtII diimine chromophores with perfluorinated thiolate ligands: nature and
      dynamics of the charge-transfer-to-diimine lowest excited state.
AB  - The synthesis of new Pt(II) diimine complexes bearing perfluorinated thiolate
      ligands, Pt(II)(NN)(4-X-C(6)F(4)-S)(2), where NN = 2,2'-bipyridine or 1,10
      phenanthroline and X = F or CN, is reported, together with an investigation of
      the nature and dynamics of their lowest excited states. A combined UV-vis,
      (spectro)electrochemical, resonance Raman, and time-resolved infrared (TRIR)
      study has suggested that the HOMO is mainly composed of thiolate(pi)/S(p)/Pt(d)
      orbitals and that the LUMO is largely localized on the pi*(diimine) orbital, thus
      revealing the [charge-transfer-to-diimine] nature of the lowest excited state. An
      enhancement of the thiolate ring vibrations, C-F vibrations, and the vibration of
      the CN-substituent on the thiolate moiety was observed in the resonance Raman
      spectra, whereas no such enhancement was seen for the nonfluorinated analogues.
      Thus, the introduction of fluorine substituents on the thiolate moiety probably
      leads to a more pronounced contribution of the intrathiolate modes to the HOMO
      compared to the analogous complexes with nonfluorinated thiolates. Furthermore,
      the introduction of the p-CN group into the thiolate moiety has allowed the
      dynamics of the lowest excited state of Pt(bpy)(4-CN-C(6)F(4)-S)(2) to be
      monitored by picosecond TRIR spectroscopy. The dynamics of the lowest [charge
      transfer-to-diimine] excited state are governed by ca. 2-ps vibrational cooling
      and 35-ps back electron transfer.

PMID- 14577777
TI  - The first coordination complexes of selenones: a structural comparison with
      complexes of sulfones.
AB  - Reactivity of the two classes of very weak donors R(2)XO(2) (X = S, R = Me (1)
      and Ph (2); X = Se, R = Me (3) and Ph (4)) have been studied. Coordination
      properties of sulfones and selenones in solution and in the gas phase have been
      compared for the first time using a model bidentate metal complex,
      [Rh(2)(O(2)CCF(3))(4)]. Two coordination modes, bridging mu(2)-O,O' and terminal
      eta(1)-O, have been detected. These types of binding were realized in two series
      of sulfone and selenone metal complexes, polymeric mono-adducts
      [Rh(2)(O(2)CCF(3))(4).(R(2)XO(2))]( infinity ) (X = S, R = Me (1a); R = Ph (2a);
      X = Se, R = Ph (4a)) and discrete bis-adducts
      [Rh(2)(O(2)CCF(3))(4).(R(2)XO(2))(2)] (X = S, R = Ph (2b); X = Se, R = Me (3b)).
      The compositions and structures of new compounds have been confirmed by NMR and
      IR spectroscopy, chemical analyses, and X-ray diffraction studies. Compounds 3b
      and 4a are the first crystallographically characterized metal complexes having
      selenone ligands coordinated to the metal centers. Preparation and X-ray study of
      analogous metal complexes of sulfone and selenone ligands allow, for the first
      time, tracking the structural changes induced by metal coordination. In addition,
      the X-ray structure of dimethyl selenone, Me(2)SeO(2) (3), an analogue of
      Me(2)SO(2), has been determined. Geometries of coordinated sulfone and selenones
      ligands have been compared with those of the corresponding "free" molecules.

PMID- 14577776
TI  - Electroswitchable photoluminescence activity: synthesis, spectroscopy,
      electrochemistry, photophysics, and X-ray crystal and electronic structures of
      [Re(bpy)(CO)3(C[triple bond]C[bond]C6H4[bond]C[triple
      bond]C)Fe(C5Me5)(dppe)][PF6](n) (n = 0, 1).
AB  - A novel heterobimetallic alkynyl-bridged complex, [Re(bpy)(CO)(3)(C[triple
      bond]C[bond]C(6)H(4)[bond]C[triple bond]C)Fe(C(5)Me(5))(dppe)], 1, and its
      oxidized species, [Re(bpy)(CO)(3)(C[triple bond]C[bond]C(6)H(4)[bond]C[triple
      bond]C)Fe(C(5)Me(5))(dppe)][PF(6)], 2, have been synthesized and their X-ray
      crystal structures determined. A related vinylidene complex,
      [Re(bpy)(CO)(3)(C[triple bond]C[bond]C(6)H(4)[bond](H)C[double
      bond]C)Fe(C(5)Me(5))(dppe)][PF(6)], 3, has also been synthesized and
      characterized. The cyclic voltammogram of 1 shows a quasireversible reduction
      couple at -1.49 V (vs SCE), a fully reversible oxidation at -0.19 V, and a
      quasireversible oxidation at +0.88 V. In accord with the electrochemical results,
      density-functional theory calculations on the hydrogen-substituted model complex
      Re(bpy)(CO)(3)(C[triple bond]C[bond]C(6)H(4)[bond]C[triple
      bond]C)Fe(C(5)H(5))(dHpe) (Cp = C(5)H(5), dHpe =
      H(2)P[bond](CH(2))(2)[bond]PH(2)) (1-H) show that the LUMO is mainly bipyridine
      ligand pi* in character while the HOMO is largely iron(II) d orbital in
      character. The electronic absorption spectrum of 1 shows low-energy absorption at
      390 nm with a 420 nm shoulder in CH(2)Cl(2), while that of 2 exhibits less
      intense low-energy bands at 432 and 474 nm and additional low-energy bands in the
      NIR at ca. 830, 1389, and 1773 nm. Unlike the related luminescent rhenium(I)
      alkynyl complex [Re(bpy)(CO)(3)(C[triple bond]C[bond]C(6)H(4)[bond]C[triple
      bond]C[bond]H)], 4, complex 1 is found to be nonemissive, and such a phenomenon
      is attributed to an intramolecular quenching of the emissive d pi(Re) -->
      pi*(bpy) (3)MLCT state by the low-lying MLCT and LF excited states of the iron
      moiety. Interestingly, switching on of the luminescence property derived from the
      d pi(Re) --> pi*(bpy) (3)MLCT state can be demonstrated in the oxidized species 2
      and the related vinylidene analogue 3 due to the absence of the quenching
      pathway.

PMID- 14577778
TI  - Structural studies on the stepwise chelating processes of bidentate 2
      (aminomethyl)pyridine and tridentate bis(2-pyridylmethyl)amine toward an acetate
      bridged dirhodium(II) center.
AB  - Several intermediates and final products of the reactions of [Rh(2)(mu
      CH(3)COO)(4)(CH(3)OH)(2)] with a tridentate ligand bis(2-pyridylmethyl)amine
      (bpa) and bidentate 2-(aminomethyl)pyridine (amp) have been isolated, and the
      chelation processes of these ligands to the dirhodium(II) center are discussed.
      The reaction of a 2 equiv amount of bpa in chloroform afforded three products,
      [Rh(2)(mu-CH(3)COO)(2)(eta(1)-CH(3)COO)(bpa)(2)](+) ([1]+), C(2)-[Rh(2)(mu
      CH(3)COO)(2)(bpa)(2)](2+) ([2a](2+)), and C(s)-[Rh(2)(mu
      CH(3)COO)(2)(bpa)(2)](2+) ([2b](2+)), where C(2) and C(s) denote the molecular
      symmetry of the two geometrical isomers. X-ray crystallography revealed that
      [1](+) contains ax-eq chelated bidentate and ax-eq-eq tridentate bpa and that
      [2a](2+) and [2b](2+) have two ax-eq-eq tridentate bpa ligands (ax denotes the
      site trans to the Rh-Rh bond, and eq, the site perpendicular to it). The reaction
      is initiated by almost instantaneous monodentate or inter-Rh(2)-unit bridging
      coordination of bpa at the ax sites, which is followed by very slow ax-eq chelate
      formation and then ultimate ax-eq-eq tridentate coordination. The reaction of
      [Rh(2)(mu-CH(3)COO)(4)(CH(3)OH)(2)] with amp in 1:2 ratio in chloroform initially
      gives an insoluble polymer in which amp interconnects the ax sites of the
      dirhodium(II) units. Further reactions afforded [Rh(2)(mu-CH(3)COO)(2)(eta(1)
      CH(3)COO)(amp)(2)](+) ([4](+)) and [Rh(2)(mu-CH(3)COO)(2)(amp)(2)](2+)
      ([5](2)(+)). The X-ray structural studies show that [4](+) has one ax-eq and one
      eq-eq chelate and [5](2)(+) two eq-eq chelates. More rigid tridentate ligands
      2,2':6',2"-terpyridine (tpy) and 4'-chloro-2,2':6',2"-terpyridine (Cl-tpy) have
      been introduced at ax sites in a monodentate mode ([Rh(2)(mu
      CH(3)COO)(4)(tpy)(2)] (8) and [Rh(2)(mu-CH(3)COO)(4)(Cl-tpy)(2)] (9)). While the
      Rh-Rh distances of these complexes and [Rh(2)(mu-CH(3)COO)(2)(2,2'
      bipyridine)(2)(py)(2)](2+) ([7](2)(+)) are practically unchanged (2.56-2.60 A)
      except for 8 and 9 (2.4 A), the Rh-N(ax) distances range from 2.11 to 2.35 A.
      Relatively short distances are found for the compounds with ax-eq or ax-eq-eq
      chelates (<2.22 A). Longest distances (2.32-2.35 A) found for 8 and 9 may be due
      to the steric effect. The distances of other complexes fall in the normal region.
      The visible band of the pi*(Rh-Rh) --> sigma*(Rh-Rh) transition in solid-state
      reflectance spectra shows a red-shift as the Rh[bond]N(ax) distances becomes
      longer.

PMID- 14577779
TI  - Fluorination of [Os3(CO)12] and [Ir4(CO)12].
AB  - Fluorination of [Os(3)CO(12)] in HF/SbF(5) affords [Os(CO)(4)(FSbF(5))(2)].
      According to its crystal structure (orthorhombic, Pna2(1), a = 1590.3(3), b =
      1036.6(1), c = 878.2(2) pm, Z = 4), the two SbF(6) units occupy cis positions in
      the octahedral environment around the Os atom. Fluorination of [Ir(4)(CO)(12)] in
      HF/SbF(5) produced three different compounds: (1) [Ir(4)(CO)(8)(mu
      F)(2)(Sb(2)F(11))(2)] (tetragonal, P4n2, a = 1285.2(2), c = 952.9(1) pm, Z = 2).
      Here, two of the six edges of the Ir(4) tetrahedron in [Ir(4)CO(12)] are replaced
      by bridging fluorine atoms. (2) [fac-Ir(CO)(3)(FSbF(5))(2)HF]SbF(6).HF
      (orthorhombic, Pnma, a = 1250.6(1), b = 1340.7(2), c = 1092.6(2) ppm, Z = 4). The
      Ir(4) tetrahedron in Ir(4)(CO)(12) is completely broken down, but the facial
      Ir(CO)(3) configuration is retained. (3) [mer-Ir(CO)(3)F(FSbF(5))(2)] (triclinic,
      P1, a = 834.9(1), b = 86 4.9(1), c = 1060.0(1) pm, alpha = 69.173(4) degrees,
      beta = 77.139(4) degrees, gamma = 88.856(4) degrees, Z = 2).

PMID- 14577780
TI  - Crystal structure and spectroscopic characterization of K8(VO)2O(SO4)6.
AB  - Red and yellow dichroistic crystals of a vanadium(V) compound, potassium (mu-oxo,
      di-mu-sulfato)bis(oxodisulfatovanadate), K(8)(VO)(2)O(SO(4))(6), have been
      obtained from the ternary catalytic model melt system
      K(2)S(2)O(7)[bond]K(2)SO(4)[bond]V(2)O(5). By slow cooling of the melt from 420
      to 355 degrees C, crystal growth occurred, using solid V(2)O(5) crystals present
      in the melt as nucleation promoter. The compound crystallizes in the monoclinic
      space group P2(l) with a = 13.60(9) A, b = 13.93(9) A, c = 14.05(9) A, beta =
      90.286(10) degrees, and Z = 2. It contains two VO(6) octahedra linked together by
      a mu-oxo and two mu-sulfato bridges. Furthermore, each octahedron has two
      monodentate sulfate ligands, making the dimeric entity coordinatively saturated.
      IR spectroscopy shows bands arising from V[bond]O[bond]V and V[double bond]O
      stretches as well as splitting of sulfate bands due to the different degrees of
      freedom present for different conformations of sulfate ligands. The coordination
      of vanadium in K(8)(VO)(2)O(SO(4))(6) is discussed in relation to the reaction
      mechanism of SO(2) oxidation catalysis.

PMID- 14577781
TI  - Structural changes, P-P bond energies, and homolytic dissociation enthalpies of
      substituted diphosphines from quantum mechanical calculations.
AB  - The molecular structures of the diphosphines P(2)[CH(SiH(3))(2)](4),
      P(2)[C(SiH(3))(3)](4), P(2)[SiH(CH(3))(2)](4), and P(2)[Si(CH(3))(3)](4) and the
      corresponding radicals P[CH(SiH(3))(2)](2), P[C(SiH(3))(3)](2),
      P[SiH(CH(3))(2)](2), and P[Si(CH(3))(3)](2) were predicted by theoretical quantum
      chemical calculations at the HF/3-21G*, B3LYP/3-21G*, and MP2/6-31+G* levels. The
      conformational analyses of all structures found the gauche conformers of the
      diphosphines with C(2) symmetry to be the most stable. The most stable conformers
      of the phosphido radicals were also found to possess C(2) symmetry. The
      structural changes upon dissociation allow the release of some of the energy
      stored in the substituents and therefore contribute to the decrease of the P-P
      bond dissociation energy. The P-P bond dissociation enthalpies at 298 K in the
      compounds studied were calculated to vary from -11.4 kJ mol(-1)
      (P(2)[C(SiH(3))(3)](4)) to 179.0 kJ mol(-1) (P(2)[SiH(CH(3))(2)](4)) at the
      B3LYP/3-21G* level. The MP2/6-31+G* calculations predict them to be in the range
      of 52.8-207.9 kJ mol(-1). All the values are corrected for basis set
      superposition error. The P-P bond energy defined by applying a mechanical analogy
      of the flexible substituents connected by a spring shows less variation, between
      191.3 and 222.6 kJ mol(-1) at the B3LYP/3-21G level and between 225.6 and 290.4
      kJ mol(-1) at the MP2/6-31+G* level. Its average value can be used to estimate
      bond dissociation energies from the energetics of structural relaxation.

PMID- 14577782
TI  - Electrochemistry of niobium(V) in sulfuric and methanesulfonic acids: formation
      of the Nb3O2(SO4)6(H2O)(3)(5-) cluster and designed electrochemical generation of
      "Nb3O2" core clusters by double potential pulse electrolysis.
AB  - The electrochemical and spectroelectrochemical properties of niobium(V) and the
      Nb(3)O(2)(SO(4))(6)(H(2)O)(3)(5-) cluster in sulfuric acid and methanesulfonic
      acid were investigated using cyclic voltammetry, constant potential electrolysis,
      and spectroelectrochemistry. These chemical systems were suitable to probe the
      formation of "Nb(3)O(2)" core trinuclear clusters. In 9 M H(2)SO(4) the cluster
      Nb(3)O(2)(SO(4))(6)(H(2)O)(3)(5-) exhibited a reversible 1-electron reduction
      peak at E(pc) = -1.30 V vs Hg/Hg(2)SO(4) electrode, as well as a 4-electron
      irreversible oxidation peak at E(pa) = -0.45 V. Controlled potential reduction at
      E = -1.40 V produced the green Nb(3.33+) cluster anion
      Nb(3)O(2)(SO(4))(6)(H(2)O)(3)(6-). In 12 M H(2)SO(4) Nb(V) displayed two
      reduction peaks at E(pc) = -1.15 V and E(pc) = -1.30 V. It was determined that
      the first process involves a quasi-reversible 2-electron reduction. After
      reduction of Nb(V) to Nb(III) the following chemical step involves formation of
      [Nb(III)](2) dimer, which further reacts with Nb(V) to produce the
      Nb(3)O(2)(SO(4))(6(H(2)O)(3)(5-) cluster (ECC process). The second reduction peak
      at E(pc) = -1.30 V corresponds to further 2-electron reduction of Nb(III) to
      Nb(I). The electrogenerated Nb(I) species also chemically reacts with starting
      material Nb(V) to produce additional [Nb(III)](2). In 5 M H(2)SO(4), the rate of
      the second chemical step in the ECC process is relatively slower and reduction of
      Nb(V) at E = -1.45 V/-1.2 V produces a mixture of Nb(3)O(2)(SO(4))(6)(H(2)O)(3)(5
      ) and [Nb(III)](2) dimer. [Nb(III)](2) can be selectively oxidized by two 2
      electron steps at E = -0.65 V to Nb(V). However, if the oxidation is performed at
      E = -0.86 V, the product is Nb(3)O(2)(SO(4))(6)(H(2)O)(3)(5-). A double potential
      pulse electrolysis waveform was developed to direct the reduction of Nb(V) toward
      selective formation of the Nb(3)O(2)(SO(4))(6)(H(2)O)(3)(5-) cluster. Proper
      application of dc-voltage pulses alternating between E(1) = -1.45 V and E(2) = 
      0.86 V yields only the target trinuclear cluster. Analogous double potential
      pulse electrolysis of Nb(V) in methanesulfonic acid generates the "Nb(3)O(2)"
      core cluster Nb(3)O(2)(CH(3)SO(3))(6)(H(2)O)(3)(+).

PMID- 14577783
TI  - Microwave-assisted polyol synthesis of CuInTe2 and CuInSe2 nanoparticles.
AB  - Nanoparticles of the CuInTe(2) (CIT) and CuInSe(2) (CIS) alloys have been
      prepared using the microwave-assisted polyol method. In this simple and quick
      reaction the polyol is both the solvent and the reducing agent. XRD studies show
      that nanoparticles of CIT and CIS are formed in the body-centered tetragonal
      structure and their average diameters are approximately 94 and approximately 83
      nm, respectively. Electron microscopy studies show that these formed particles
      are poorly aggregated with a mean diameter of 100 and 85 nm, respectively. The
      products have been characterized by different analytical techniques, and the
      electronic properties have been measured using photoacoustic spectroscopy (PAS).

PMID- 14577784
TI  - Reduction of the allylic substituents in Ni(I)(1,8-dipropenyl-1,4,8,11
      tetraazacyclotetradecane)+ by the central Ni(I) in aqueous solutions.
AB  - The complex Ni(II)(1,8,-di-2-propenyl-1,4,8,11-tetraazacyclotetradecane)(2+),
      (NiL(1))(2+), was synthesized. X-ray crystallography demonstrates that the
      complex obtained is the trans-III isomer. The allylic substituents shift the
      redox couples (NiL(1))(3+/2+) and (NiL(1))(2+/+) anodically relative to the
      corresponding couples for Ni(II)(1,4,8,11-tetraazacyclotetradecane)(2+),
      (NiL(2))(2+), as expected. Surprisingly, the lifetime of (NiL(1))(+) in neutral
      aqueous solutions is shorter than that of (NiL(2))(+). Pulse radiolysis
      experiments reveal that the allylic substituents are reduced by the central Ni(I)
      ion. The first step in this reduction is a general acid catalyzed process. The
      results suggest that this step involves schematically the reaction
      Ni(I)[bond]NCH(2)CH[double bond]CH(2)(+) + H(+) -->
      Ni(III)[bond]NCH2CH2CH(2)(2+). The latter transient decomposes slowly with a half
      life time of several minutes. Preliminary results support the suggestion that
      (NiL(2))(+), or other Ni(I)L complexes of this family, might reduce many alkenes
      present in the solution.

PMID- 14577785
TI  - How strong can the bend be on a DNA helix from cisplatin? DFT and MP2 quantum
      chemical calculations of cisplatin-bridged DNA purine bases.
AB  - The B3LYP/6-31G(d) level of theory was used for the optimization of
      [Pt(NH(3))(4)](2+), [Pt(NH(3))(3)(H(2)O)](2+), cis-[Pt(NH(3))(2)(H(2)O)(2)](2+),
      and related platinum complexes. In addition, water or ammonium ligands were
      replaced by DNA purine bases so that finally cis-diammineplatinum with two bases
      (Pt-bridged complexes) is obtained. Single point calculations using the MP2/6
      31+G(d) method were performed on the obtained reference geometries and were
      utilized for estimating bond dissociation energies (BDEs) and stabilization
      energies, and for electron density analyses. After reoptimization, IR spectra
      were determined from HF second derivatives. It was found that replacement of both
      water and ammonium by the DNA base is an exothermic process (20-50 kcal/mol
      depending on the ligands present in the complex). Asymmetric structures with one
      interbase H-bond were obtained for cis-diammine[bond](N(7),N(7)'
      diadenine)[bond]platinum and mixed cis-diammine[bond](N(7)-adenine)[bond](N(7)
      guanine)[bond]platinum complexes. In the case of the diguanine Pt-bridge, a
      symmetrical complex with two ammonium...O(6) H-bonds was found. The higher
      stabilization energy of the di-guanine complex is linked to a larger component of
      the Coulombic interaction. However, the BDE of Pt[bond]N(7)(G) is smaller in this
      complex than the BDE of Pt[bond]N(7)(G) from the mixed Pt[bond]AG complex. Also,
      steric repulsion of the ligands is about 10 kcal/mol smaller for the asymmetrical
      Pt[bond]AA and Pt[bond]AG bridges. The influence of the trans effect on DBE can
      be clearly seen. Adenine exhibits the largest trans effect, followed by guanine,
      ammonium, and water. The strength of the H-bond can be determined from the IR
      spectra. The strongest H-bond is the interbase H-bridge between adenine and
      guanine in the mixed Pt[bond]AG complex; otherwise, the H-bonds of adenine
      complexes are weaker than in guanine complexes. BDE can be traced in the guanine
      containing complexes. The nature of the covalent bonding is analyzed in terms of
      partial charges and MO. A general explanation of the lower affinity of transition
      metals to oxygen than nitrogen can be partially seen in the less favorable
      geometrical orientation of lone electron pairs of oxygen.

PMID- 14577786
TI  - Novel ET-coordinated copper(I) complexes: syntheses, structures, and physical
      properties (ET = BEDT-TTF = Bis(ethylenedithio)tetrathiafulvalene).
AB  - New molecular charge-transfer complexes of bis(ethylenedithio)tetrathiafulvalene
      (ET), (ET)Cu(2)Br(4) (1), (ET)(2)Cu(6)Br(10) (2), (ET)(2)[Cu(4)Br(6)ET] (3),
      (ET)(2)Cu(2)Br(4) (4), (ET)(2)Cu(3)Br(7)(H(2)O) (5), and
      (ET)(2)Cu(6)Br(10)(H(2)O)(2) (6), have been synthesized by diffusing reaction of
      ET and Cu(II)Br(2). Their crystal structures and physical properties have been
      investigated. X-ray analyses revealed that ET molecules coordinated to the copper
      ions with the sulfur atoms of the ethylenedithio groups in all compounds. The Cu
      S distances are found in the range 2.268(5)-2.417(8) A, being close to the
      typical Cu(I)-S coordination bond distances. Strong d-pi interactions between d
      electrons of the copper ions and pi-electrons of the ET molecules can be expected
      through the Cu-S coordination bonds. ET molecules behave as trans-bidentate
      ligands bonding to two different copper ions in 1 and 3, as cis-bidentate ligands
      in 2, 5, and 6, and as monodentate ligands in 4. In the crystal structure of 3,
      there are two types of ET molecules in the crystal structure, where the first
      type is a trans-bidentate ligand and the second forms a stacking structure by
      itself. Compounds 1, 2, 4, and 6 show semiconducting behavior down to low
      temperature (sigma(RT) = 1.6 x 10(-2) S cm(-1) and E(a) = 122 meV for 1,
      sigma(RT) = 2.1 S cm(-1) and E(a) = 21 meV for 2, sigma(RT) = 5.4 x 10(-4) S cm(
      1) and E(a) = 239 meV for 4, and sigma(RT) = 5.1 x 10(-2) S cm(-1) and E(a) = 207
      meV for 6). On the other hand, in 3, a metal-like region is observed along the b
      axis and c-axis, due to the contribution of stacked ET molecules, and a metal
      semiconductor transition occurs at 280 and 270 K, respectively. Also, 5 exhibits
      metallic conductivity in the temperature ranges 240-300 and 200-300 K along the b
      axis and c-axis, respectively, despite the oxidation state of ET with 2+.

PMID- 14577787
TI  - Bis(pyrazol-1-yl)acetates as tripodal heteroscorpionate ligands in iron
      chemistry: syntheses and structures of iron(II) and iron(III) complexes with
      bpza, bdmpza, and bdtbpza ligands.
AB  - The molecular structure of the previously reported species "[Fe(bdtbpza)Cl]" has
      been revealed by X-ray structure determination to be a ferrous dimer
      [Fe(bdtbpza)Cl](2) (2c) [bdtbpza = bis(3,5-di-tert-butylpyrazol-1-yl)acetate].
      The syntheses of ferrous 2:1 complexes [Fe(bpza)(2)] (3a) and [Fe(bdtbpza)(2)]
      (3c) as well as ferric 1:1 complexes [NEt(4)][Fe(bpza)Cl(3)] (4a) and
      [NEt(4)][Fe(bdmpza)Cl(3)] (4b) [bpza = bis(pyrazol-1-yl)acetate, bdmpza = bis(3,5
      dimethylpyrazol-1-yl)acetate] are reported. Complexes 3a, previously reported
      [Fe(bdmpza)(2)] (3b), and 3c are high-spin. No spin crossover to the low-spin
      state was observed in the temperature range of 5-350 K. 4a and 4b are synthesized
      in one step and in high yield from [NEt(4)](2)[Cl(3)FeOFeCl(3)]. 4a and 4b are
      iron(III) high-spin complexes. Crystallographic information: 2c
      (C(24)H(39)ClFeN(4)O(2).CH(2)Cl(2).CH(3)CN) is triclinic, P1, a = 12.171(16) A, b
      = 12.851(14) A, c = 13.390(13) A, alpha = 98.61(9) degrees, beta = 113.51(11)
      degrees, gamma = 108.10(5) degrees, Z = 2; 3a (C(8)H(7)Fe(0.5)N(4)O(2)) is
      monoclinic, P2(1)/n, a = 7.4784(19) A, b = 7.604(3) A, c = 16.196(4) A, beta =
      95.397(9) degrees, Z = 4; 3c (C(24)H(39)Fe(0.5)N(4)O(2)) is monoclinic, P2(1)/n,
      a = 9.939(6) A, b = 18.161(10) A, c = 13.722(8) A, beta = 97.67(7) degrees, Z =
      4; 4b (C(20)H(35)Cl(3)FeN(5)O(2)) is monoclinic, C2/c, a = 30.45(6) A, b =
      12.33(2) A, c = 16.17(3) A, beta = 118.47(5) degrees, Z = 8.

PMID- 14577788
TI  - Mixed-spin binuclear nickel(II) complexes in unsymmetrical ligand environments
      and related mononuclear compounds: electronic and molecular structures in
      solution and in the solid state.
AB  - Nickel(II) complexes of three new heterodonor ligands (HL(1), H(2)L(2), and
      H(3)L(3)) based on 2-aminocyclopent-1-ene-1-dithiocarboxylate have been
      synthesized, and their crystallographic characterizations are reported. With the
      pentacoordinating ligands HL(1) and H(3)L(3), the products obtained (1 and 2) are
      both mononuclear square planar compounds in which one of the pyrazolyl arms of
      ligand HL(1) and the bridgehead alkoxy oxygen of H(3)L(3) are staying away from
      coordination in 1 and 2, respectively. The saturated three carbon alkanyl chain
      in the ligand H(3)L(3) provides enough flexibility to generate tetrahedral
      distortion (dihedral angle, 22.7 degrees ) in the planarity of 2. Compound 1
      displays paramagnetic line-broadening in its (1)H NMR spectrum due to
      oligomerization in solution. With the unsymmetrical binucleating ligand H(2)L(2),
      two mixed-spin homodinuclear complexes (3 and 4) have been synthesized using
      pyrazole and 2-mercaptopyridine as ancillary mu(2)-bridging ligands. Both these
      complexes have square planar low-spin and spin-triplet nickel(II) centers which
      display both coordination number and donor set asymmetry in tandem. The compounds
      have been characterized by (1)H NMR, electronic spectroscopy, and electrochemical
      studies.

PMID- 14577789
TI  - Tropochemical cell-twinning in the new quaternary bismuth selenides KxSn(6
      2x)Bi(2+x)Se9 and KSn5Bi5Se13.
AB  - The quaternary K(x)Sn(6-2x)Bi(2+x)Se(9) and KSn(5)Bi(5)Se(13) were discovered
      from reactions involving K(2)Se, Bi(2)Se(3), Sn, and Se. The single crystal
      structures reveal that K(x)Sn(6-2x)Bi(2+x)Se(9) is isostructural to the mineral
      heyrovskyite, Pb(6)Bi(2)S(9), crystallizing in the space group Cmcm with a =
      4.2096(4) A, b = 14.006(1) A, and c = 32.451(3) A while KSn(5)Bi(5)Se(13) adopts
      a novel monoclinic structure type (C2/m, a = 13.879(4) A, b = 4.205(1) A, c =
      23.363(6) A, beta = 99.012(4) degrees ). These compounds formally belong to the
      lillianite homologous series xPbS.Bi(2)S(3), whose characteristic is derivation
      of the structure by tropochemical cell-twinning on the (311) plane of the NaCl
      type lattice with a mirror as twin operation. The structures of K(x)Sn(6
      2x)Bi(2+x)Se(9) and KSn(5)Bi(5)Se(13) differ in the width of the NaCl-type slabs
      that form the three-dimensional arrangement. While cell-twinning of 7 octahedra
      wide slabs results in the heyrovskyite structure, 4 and 5 octahedra wide slabs
      alternate in the structure of KSn(5)Bi(5)Se(13). In both structures, the Bi and
      Sn atoms are extensively disordered over the metal sites. Some physicochemical
      properties of K(x)Sn(6-2x)Bi(2+x)Se(9) and KSn(5)Bi(5)Se(13) are reported.

PMID- 14577790
TI  - Comparison of M[bond]S, M[bond]O, and M[bond](eta 2-SO) structures and bond
      dissociation energies in d6 (CO)5M(SO2)nq complexes using density functional
      theory.
AB  - Density functional theory studies of the series of isomeric d(6)
      (pentacarbonyl)metal complexes (CO)(5)M(eta(1)-SO(2))(nq), (CO)(5)M(eta(1)
      OSO)(nq)(), and (CO)(5)M(eta(2)-SO(2))(nq) (M = Ti-Hf, nq = 2-; M = V-Ta, nq = 1
      ; M = Cr -W, nq = 0; M = Mn-Re, nq = 1+; M = Fe-Os, nq = 2+) provide accurate
      structural modeling and quantitative prediction of the relative stabilities of
      the isomers. The eta(1)-S-bound complexes display planar SO(2) moieties that
      adopt staggered orientations with respect to the carbonyl ligands, in keeping
      with experimental observations. The OSO chain in the eta(1)-O-bound complexes
      generally adopts the u-shape with a staggered orientation. The dianions
      (CO)(5)(Ti-Hf)(eta(1)-OSO)(2-) differ in that the OSO chain adopts the eclipsed z
      shape orientation. The eta(2)-SO(2) complexes exhibit a facial interaction and
      are stable only for anionic and neutral complexes, supporting the view that this
      motif involves substantial M --> SO(2) pi-back-bonding. The relative stabilities
      of the isomers generally follow u-shaped trends both across a row and down a
      family. This fits with qualitative ideas that the bond dissociation energies
      (BDEs) for the (CO)(5)M(SO(2))(nq) complexes track competition between relative
      hardness/softness of the metal fragment and its capacity for pi-back-bonding.
      Quantitatively, examination of BDEs by bond energy decomposition approaches
      suggests that electrostatic considerations dominate bonding for the eta(1)-SO(2)
      complexes and covalent effects dominate for the eta(2)-SO(2) species, while both
      are important for eta(1)-OSO complexes.

PMID- 14577791
TI  - Reactions of palladium germylene complexes: formation of sulfide bridges.
AB  - Reactivity of three novel Pd germylene species is presented.
      (Et(3)P)(2)PdGe[N(SiMe(3))(2)](2) (1) and (dppe)PdGe[N(SiMe(3))(2)](2) (6) react
      with COS to give the sulfide bridged species (Et3P)2Pd(mu S)Ge[N(SiMe3)2]2 (2)
      and (dppe)Pd(mu S)Ge-[N(SiMe3)2]2 (7) (dppe = (diphenylphosphino)ethane).
      (Ph(3)P)(2)PdGe[N(SiMe(3))(2)](2) (4) reacts with COS to give the disulfide
      bridged complex (Ph(3)P)(2)Pd(muS)(2)Ge[N(SiMe(3))(2)](2) (5) resulting in Pd-Ge
      bond cleavage. This phosphine dependent reactivity is explored. Crystal
      structures of 2, 5, 7, and the dimeric form of complex 2, (8), are reported. In
      the presence of excess germylene, complexes 2 and 5 are shown to partially
      regenerate their parent palladium germylene complexes, 1 and 4, respectively, via
      photolysis or heating.

PMID- 14577792
TI  - Diphosphines possessing electronically different donor groups: synthesis and
      coordination chemistry of the unsymmetrical Di(N-pyrrolyl)phosphino
      functionalized dppm analogue Ph2PCH2P(NC4H4)2.
AB  - The unsymmetrical diphosphinomethane ligand Ph(2)PCH(2)P(NC(4)H(4))(2) L has been
      prepared from the reaction of Ph(2)PCH(2)Li with PCl(NC(4)H(4))(2). The
      diphenylphosphino group can be selectively oxidized with sulfur to give
      Ph(2)P(S)CH(2)P(NC(4)H(4))(2) 1. The reaction of L with [MCl(2)(cod)] (M = Pd,
      Pt) gives the chelate complexes [MCl(2)(L-kappa(2)P,P')] (2, M = Pd; 3, M = Pt)
      in which the M-P bond to the di(N-pyrrolyl)phosphino group is shorter than that
      to the corresponding diphenylphosphino group. However, the shorter Pd-P bond is
      cleaved on reaction of 2 with an additional 1 equiv of L to give [PdCl(2)(L
      kappa(1)P)(2)] 4. Complex 4 reacts with [PdCl(2)(cod)] to regenerate 2, and with
      [Pd(2)(dba)(3)].CHCl(3) to give the palladium(I) dimer [Pd(2)Cl(2)(mu-L)(2)] 5,
      which exists in solution and the solid state as a 1:1 mixture of head-to-head
      (HH) and head-to-tail (HT) isomers. The palladium(II) dimer
      [Pd(2)Cl(2)(CH(3))(2)(mu-L)(2)] 6, formed by the reaction of [PdCl(CH(3))(cod)]
      with L, also exists in solution as a mixture of HH and HT isomers, although in
      this case the HT isomer prevails at low temperature and crystallizes
      preferentially. Complex 6 reacts with TlPF(6) to give the A-frame complex
      [Pd(2)(CH(3))(2)(mu-Cl)(mu-L)(2)]PF(6) 7. The reaction of L with [RuCp*(mu(3)
      Cl)](4) leads to the dimer [Ru(2)Cp*(2)(mu-Cl)(2)(mu-L)] 8, for which the
      enthalpy of reaction has been measured. The reaction of L with [Rh(mu
      Cl)(cod)](2) gives a mixture of compounds from which the dimer [Rh(2)(mu
      Cl)(cod)(2)(mu-L)]PF(6) 9 can be isolated. The crystal structures of 2.CHCl(3),
      3.CH(2)Cl(2), 4, 5.(1)/(4)CH(2)Cl(2), 6, 7.2CH(2)Cl(2), 8, and 9.CH(2)Cl(2) are
      reported.

PMID- 14577793
TI  - Facile Ni(II)/ketoxime-mediated conversion of organonitriles into imidoylamidine
      ligands. Synthesis of imidoylamidines and acetyl amides.
AB  - Treatment of alkyl nitriles with NiX(2).6H(2)O (X = Cl, NO(3)) and 2-propanone
      oxime, followed by (X = Cl) addition of [i-Pr(4)N](NO(3)) for precipitation of
      the product, resulted in the formation of amidinium nitrates [RC([double
      bond]NH(2))NH(2)](NO(3)) (R = Me, Et, n-Pr). The reaction went to another
      direction with NiX(2).2H(2)O, i.e., the reaction between neat RCN (R = Me, Et, n
      Pr, i-Pr, n-Bu, CH(2)Cl, CH(2)C(6)H(4)OMe-p) and NiCl(2).2H(2)O/2-propanone oxime
      (other ketoximes can also be used) gave the (imidoylamidine)Ni(II) complexes
      [Ni[N(H)[double bond]C(R)NHC(R)[double bond]NH](2)](2+) (1(2+)-7(2+)). The latter
      were isolated in good yields (65-91%) as the bis-chloride salts 1.Cl(2)-6.Cl(2)
      and the mixed salt 7.(Cl)(p-MeOC(6)H(4)CH(2)CO(2)). Remarkably, the latter
      transformation does not proceed at all if NiCl(2).2H(2)O or the ketoxime are
      taken alone. Liberation of imidoylamidines was performed for one alkyl-containing
      complex [2.Cl(2)] and one benzyl-containing complex [7.(Cl)(p
      MeOC(6)H(4)CH(2)CO(2))], by (i) addition of HBF(4).Et(2)O to the acetonitrile
      solution of the complexes to yield [N(H)[double bond]C(R)NHC(R)[double
      bond]NH].2HBF(4) (R = Et 8 and R = CH(2)C(6)H(4)OMe-p 9) or (ii) substitution for
      ethanediamine (en) with following precipitation of the complex [Ni(en)(3)]Cl(2)
      with formation of free N(H)[double bond]C(R)NHC(R)[double bond]NH (R = Et 10 and
      R = CH(2)C(6)H(4)OMe-p 11). In contrast to the liberation in nonaqueous media,
      treatment of 2.Cl(2) and 7.(Cl)(p-MeOC(6)H(4)CH(2)CO(2)) with Na(2)EDTA.2H(2)O in
      water-methanol solutions led to substitution and hydrolysis to furnish the acyl
      amides [EtC([double bond]O)](2)NH (12) and [p-MeOC(6)H(4)CH(2)C([double
      bond]O)](2)NH (13). Alternatively, 12 and 13 were obtained by hydrolysis of 10
      and 11 in water at pH ca. 8.5. It was shown that the oxime complexes trans
      [NiCl(2)(C(4)H(8)C[double bond]NOH)(4)] (14) or cis-[Ni(O,O
      NO(3))(2)(C(4)H(8)C[double bond]NOH)(2)] (15) can be intermediates in the
      formation of amidines and imidoylamidines. The sequence of the Ni(II)/oxime
      mediated formation of (imidoylamidine)Ni complexes and liberation (or hydrolytic
      liberation) of the ligands opens up a novel, facile and environmentally benign
      route to imidoylamidines and acyl amides.

PMID- 14577794
TI  - Kinetic stability of the peroxidase activity of unfolded cytochrome c: heme
      degradation and catalyst inactivation by hydrogen peroxide.
AB  - Unfolding converts Paracoccus versutus cytochrome c-550 into a potent peroxidase
      (Diederix, R. E. M.; Ubbink, M.; Canters, G. W. ChemBioChem 2002, 3, 110-112).
      The catalytic activity is accompanied by peroxide-driven inactivation that is
      prevented, in part, by reducing substrate. Here, the kinetics of inactivation are
      described, and evidence is presented for the occurrence of a labile intermediate
      on the catalytic peroxidase pathway of unfolded cytochrome c-550. This
      intermediate represents a branching point, whereby the protein proceeds along
      either the productive pathway or self-inactivates. Reducing substrate suppresses
      inactivation by decreasing the steady-state concentration of the labile
      intermediate. Inactivation is accompanied by heme degradation. Its chemical
      reactivity, UV-vis, and EPR properties identify the first intermediate as
      hydroxyheme-cytochrome c-550, i.e. with heme hydroxylated at one of the heme meso
      positions. The occurrence of this species argues for the peroxo-iron species in
      the peroxidase mechanism as the labile intermediate leading to inactivated
      cytochrome c-550.

PMID- 14577795
TI  - Cr(III)(salen)Cl catalyzed asymmetric epoxidations: insight into the catalytic
      cycle.
AB  - Intermediates of chromium-salen catalyzed alkene epoxidations were studied in
      situ by EPR, (1)H and (2)H NMR, and UV-vis/NIR spectroscopy (where chromium
      salens were (S,S)-(+)-N,N'-bis(3,5-di-tert-butylsalicylidene)-1,2
      cyclohexanediamino chromium(III) chloride (1) and racemic N,N'-bis(3,4,5,6-tetra
      deuterosalicylidene)-1,2-cyclohexanediamino chromium(III) chloride (2)). High
      valence chromium complexes, intermediates of epoxidation reactions, were detected
      and characterized by EPR and NMR. They are the reactive mononuclear
      oxochromium(V) intermediate (A) Cr(V)O(salen)L (where L = Cl(-) or a solvent
      molecule) and an inactive chromium-salen binuclear complex (B) which acts as a
      reservoir of the active species. The latter complex demonstrates an EPR signal
      characteristic of oxochromium(V)-salen species and (1)H NMR spectra typical for
      chromium(III)-salen complexes, and it is identified as mixed-valence binuclear
      L(1)(salen)Cr(III)OCr(V)(salen)L(2) (L(1), L(2) = Cl(-) or solvent molecules).
      The intermediates Cr(V)O(salen)L and L(1)(salen)Cr(III)OCr(V)(salen)L(2) exist in
      equilibrium, and their ratio can be affected by addition of donor ligands (DMSO,
      DMF, H(2)O, pyridine). Addition of donor additives increases the fraction of A
      over that of B. The same two complexes can be obtained with m-CPBA as oxidant.
      Reactivities of the Cr(V)O(salen)L complexes toward E-beta-methylstyrene were
      measured in DMF. The L(1)(salen)Cr(III)OCr(V)(salen)L(2) intermediate has been
      proposed to be a reservoir of the true reactive chromium(V) species. The chromium
      salen catalysts demonstrate low turnover numbers (ca. 5), probably due to ligand
      degradation processes.

PMID- 14577796
TI  - Reactivity of dioxoosmium(VI) porphyrins toward arylhydrazine. Isolation of
      hydrazidoosmium and amidoosmium porphyrins.
AB  - Reactions of dioxoosmium(VI) porphyrins [Os(VI)(Por)O(2)] with excess 1,1
      diphenylhydrazine in tetrahydrofuran at ca. 55 degrees C for 15 min afforded
      bis(hydrazido(1-))osmium(IV) porphyrins [Os(IV)(Por)(NHNPh(2))(2)] (1a, Por = TPP
      (meso-tetraphenylporphyrinato dianion); 1b, Por = TTP (meso-tetrakis(p
      tolyl)porphyrinato dianion)), hydroxo(amido)osmium(IV) porphyrins
      [Os(IV)(Por)(NPh(2))(OH)] (2a, Por = TPP; 2b, Por = TTP), and bis(hydrazido(2
      ))osmium(VI) porphyrin [Os(VI)(Por)(NNPh(2))(2)] (3c, Por = TMP (meso
      tetramesitylporphyrinato dianion)). The same reaction under harsher conditions
      (in refluxing tetrahydrofuran for ca. 1 h) gave a nitridoosmium(VI) porphyrin,
      [Os(VI)(Por)(N)(OH)] (4b, Por = TTP). Oxidation of 1a,b with bromine in
      dichloromethane afforded bis(hydrazido(2-)) complexes [Os(VI)(TPP)(NNPh(2))(2)]
      (3a) and [Os(VI)(TTP)(NNPh(2))(2)] (3b), respectively. All the new osmium
      porphyrins were identified by (1)H NMR, IR, and UV-vis spectroscopy and mass
      spectrometry; the structure of 2b was determined by X-ray crystallography (Os
      NPh(2) = 1.944(6) A, Os-OH = 1.952(5) A).

PMID- 14577797
TI  - Volatile beta-ketoiminato- and beta-diketiminato-based zirconium complexes as
      potential MOCVD precursors.
AB  - An amine elimination pathway has been used to produce a number of homo- and
      heteroleptic zirconium complexes, starting from tetrakis(dialkylamido)zirconium
      complexes and beta-diketimine or, alternatively, Schiff Base compounds. Reaction
      of 2 equiv of the bidentate beta-diketimine (2Z,4E)-N-methyl-4-(methylimino)pent
      2-en-2-amine with Zr(NR(2))(4) (R = Me, Et) affords the six-coordinate
      heteroleptic compounds bis(N-methyl-4-(methylimino)pent-2-en-2
      amido)bis(dialkylamido)zirconium 1 (alkyl = Me) and 2 (alkyl = Et). The dynamic
      behavior of these two compounds in solution has been investigated. Reaction with
      the isopropyl-substituted beta-diketimine (2Z)-N-isopropyl-4-(isopropylimino)pent
      2-en-2-amine gives the five-coordinate mono(diketiminato)-substituted compound (N
      isopropyl-4-(isoropylimino)pent-2-en-2-amido)tris(dimethylamido )zirconium, 3.
      With employment of the Schiff base (3Z)-4-(methylamino)pent-3-en-2-one, it was
      also possible to prepare the six-coordinate bis(4-(methylamino)pent-3-en-2
      onato)bis(diethylamido)zirconium compound 4. When the bidentate ligand bearing
      hydrogen as substituent on the imino-nitrogen atom was employed, homoleptic
      tetrakis(beta-ketoiminato)- and tetrakis(beta-diketiminato)zirconium compounds 5
      and 6 can be obtained. Complexes 1 and 5 have been tested for their air stability
      with reference to Zr(NMe(2))(4). The stability order turned out to be 1 > 5 >>
      Zr(NMe(2))(4). The thermal properties and volatility of all the compounds are
      discussed in view of their potential application in metal-organic chemical vapor
      deposition processes (MOCVD) of zirconium nitride.

PMID- 14577798
TI  - Crystal structures of rubidium and cesium anthranilates and salicylates.
AB  - In an attempt to probe a potential template role of the large alkali-metal
      cations rubidium and cesium in the organization of biorelevant ligands,
      salicylate and anthranilate complexes of the two elements were prepared and
      structurally investigated. The studies were also expected to show the marked
      structural differences compared to the corresponding thallium(I) compounds.
      Rubidium anthranilate and cesium salicylate could be crystallized as the
      monohydrates Rb(Anth)(H(2)O) and Cs(Sal)(H(2)O). Both have layer structures
      containing the cations and the polar groups of the ligands in core domains
      sandwiched by the aromatic rings above and below. The metal atoms have
      coordination numbers 7 and 8, respectively, with an irregular coordination sphere
      made up exclusively of oxygen atoms. Crystalline material with a 1:2
      stoichiometry, Cs[H(Anth)(2)], is obtained from aqueous solutions of Cs(Anth)
      upon absorption of carbon dioxide with concomitant formation of cesium
      bicarbonate, Cs(HCO(3)). The crystal structure of Cs(HCO(3)) was redetermined to
      obtain precise benchmark data for cesium carbonates and carboxylates. The cesium
      hydrogen bisanthranilate also has a layer structure with eight-coordinate cesium
      atoms. The coordination sphere includes one nitrogen donor atom. The organization
      of all layer structures appears to be governed mainly by steric effects and
      electrostatic forces with very little directional influence of the cations. This
      result suggests that the large alkali metals have no efficient template effect
      for the organization of biological substrates and can explain the low toxicity of
      rubidium and cesium salts.

PMID- 14577799
TI  - Unusual coordination assemblies from platinum(II) thienyl and bithienyl
      complexes.
AB  - Dinuclear Pt(2)Br(2)(dppf)(2)(mu-C(8)H(4)S(2)) exchanges with isonicotinic acid
      to release free bithiophene and gives a molecular square [Pt(4)(dppf)(4)(mu(2)
      O(2)CC(5)H(4)N)(4)](4+)4OTf(-) which is an "all-ring" system with four Pt rings
      disposed at the corners of a larger macrocyclic ring. The related mononuclear
      complex PtBr(eta(1)(C2)-C(4)H(3)S)(dppf) reacts with AgOTf (OTf = triflate) to
      give [Pt(2)(dppf)(2)(mu(2),eta(1)(C),eta(1)(S)-C(4)H(3)S)(2)](2+)2OTf(-) with an
      unusual six-membered ring formed by the fusion of two Pt-thienyl entities at the
      sulfur sites. All the complexes are structurally characterized by single-crystal
      X-ray crystallography.

PMID- 14577800
TI  - Trifluoromethyl chlorosulfonate, CF3OSO2Cl: gas phase and crystal structure,
      conformation and vibrational analysis studied by experimental and theoretical
      methods.
AB  - The geometric structure and conformational properties of trifluoromethyl
      chlorosulfonate (chlorosulfuric acid trifluoromethyl ester), CF(3)OSO(2)Cl, have
      been determined by X-ray crystallography, gas electron diffraction (GED), and
      vibrational spectroscopy (IR(gas), IR(matrix), and Raman(liquid)). These
      experimental investigations were supplemented by quantum chemical calculations
      (B3LYP with 6-311G* and 6-311+G(3df) basis sets). All experimental methods result
      in a single conformer with gauche orientation of the CF(3) group relative to the
      S[bond]Cl. The dihedral angle delta(COSCl) is determined to be 91.7(3) degrees in
      the crystal and 94(3) degrees in the gas phase. This dihedral angle corresponds
      to a near-eclipsed orientation of the O[bond]C relative to one of the S[double
      bond]O bonds (delta(CO[bond]SO) = -23.0(3) degrees and -21(3) degrees in the
      crystal and gas phase, respectively).

PMID- 14577801
TI  - Novel mixed-valence heteropolyoxometalates: a molybdenum diphosphonate anion
      [MoV7MoVIO16(O3PPhPO3H)4]3- and its one- and two-dimensional assemblies.
AB  - A novel mixed-valence polyoxomolybdenum anion,
      [Mo(V)(7)Mo(VI)O(16)(O(3)PPhPO(3)H)(4)](3)(-), was synthesized hydrothermally
      from molybdenum oxide, molybdenum metal, boric and phosphoric acids, 1,2
      phenyldiphosphonic acid, and imidazole (ImH) and was structurally characterized
      as an imidazolium salt (orthorhombic, Aba2; a = 16.674(4), b = 17.238(1), and c =
      24.81(2) A). One- and two-dimensional structures of this anion and additional
      molybdenum diphosphonate linkers were assembled as well. They were structurally
      characterized as their pyridinium (pyH) salts
      (pyH)(4)[[Mo(V)(7)Mo(VI)O(16)(O(3)PPhPO(3))(2)(O(3)PPhPO(3)H)(2)][Mo(2)O(4)(OH)(H
      (3)PPhPO(3)H)]].5H(2)O (monoclinic, P2(1)/c; a = 20.8506(9), b = 22.866(1), and c
      = 21.1403(9) A; beta = 118.7087(8) degrees ) and
      (pyH)(3)[[Mo(V)(7)Mo(VI)O(16)(O(3)PPhPO(3))(4)][Mo(2)O(2)(OH)(2)(HO(3)PPhPO(3)H)]
      .3H(2)O (orthorhombic, Pca2(1); a = 19.057(1), b = 20.402(2), and c = 20.660(2)
      A). The compounds were also characterized by IR spectroscopy and magnetic
      measurements.

PMID- 14577802
TI  - Structure and properties of a novel 3D straight-channel polyoxovanadate and an
      unexpected trimeric barbiturate obtained by hydrothermal reactions.
AB  - The hydrothermal reaction of NaVO(3).H(2)O, barbituric acid, NH(2)NH(2).2HCl,
      H(3)PO(4), and H(2)O gave a novel heteropolyoxovanadate
      Na(6)[(P(V)O(4))V(V)(6)V(IV)(12)O(39)](2).H(3)PO(4).31H(2)O (1) and an unexpected
      phase Na(2)[C(12)H(6)N(6)O(9)].7H(2)O (2). The basic building blocks in 1 are the
      six-capped sphere-shaped heteropoly anion [(P(V)O(4))V(V)(6)V(IV)(12)O(39)](3-)
      with framework similar to that of the reported polyoxovanadates possessing
      [V(18)O(42)] clusters encapsulating VO(4) or other ions. These heterpoly anionic
      units are linked via V[bond]O[bond]V bridges into an interesting 3D straight
      channel structure. The structure of 2 consists of novel organic anions
      ([C(12)H(6)N(6)O(9)](2-), 5,5-bis(2',4',6'-trioxopyrimidyl)barbital, representing
      the first oxidized barbituric acid trimer) linked via sodium ions into 1D hollow
      tubes with diameter of 4.49 x 6.86 A and further connected into a three
      dimensional framework via hydrogen bonds.

PMID- 14577803
TI  - Synthesis, structure, and magnetoresistance of SmPd2Ga2.
AB  - Single crystals of a new ternary compound, SmPd(2)Ga(2), have been synthesized by
      flux growth methods. This compound adopts a tetragonal space group I4/mmm, Z = 2,
      with lattice parameters a = 4.2170(3) A and c = 10.4140(3) A. The crystal
      structure is composed of layers of isolated Sm atoms and layers of PdGa(4) edge
      sharing tetrahedra alternating along the c-axis. The sample is metallic (d rho/dT
      > 0) with a weak temperature dependence above 100 K. This new material has
      physical properties similar to those of other Sm intermetallics and has, most
      notably, a large positive magnetoresistance at low temperatures. Magnetic
      measurements indicate that SmPd(2)Ga(2) is ferromagnetic with T(c) approximately
      5 K.

PMID- 14577804
TI  - MA(delta)Sb(2-delta) (M = Zr, Hf; A = Si, Ge): a new series of ternary
      antimonides and not "beta-ZrSb2".
AB  - The ternary antimonides ZrSi(delta)Sb(2-delta), HfGe(delta)Sb(2-delta), and
      ZrGe(delta)Sb(2-delta) were prepared by annealing of the elements in
      stoichiometric ratios below 800 degrees C. ZrSi(delta)Sb(2-delta) was earlier
      erroneously described as the binary "beta-ZrSb(2)", which does not exist as such,
      because the incorporation of tetrel atoms is necessary for the formation of this
      structure. ZrSi(delta)Sb(2-delta) has a small yet significant phase width with at
      least 0.066(7) < or = delta < or = 0.115(3), whereas the Ge analogues exist with
      larger tetrel concentration, i.e., ZrGe(0.211(5))Sb(1.789) and
      HfGe(0.205(6))Sb(1.795). The whole series of title compounds crystallizes in the
      Co(2)Si type (space group Pnma), with lattice dimensions of, e.g., for
      ZrGe(0.211(5))Sb(1.789), a = 730.4(1) pm, b = 395.13(6) pm, c = 957.6(2) pm, V =
      0.27635(7) nm(3), Z = 4. The anionic substructure comprises infinite ribbons
      formed by the atom sites Q1 and Sb2, with Q1 being mixed occupied by Si or Ge and
      Sb atoms. These ribbons exhibit Q1-Q1 single bonds and Q1-Sb2 "half" bonds.
      Assuming the validity of the 8 - N rule, one can assign seven valence-electrons
      to Sb2 but only five to Q1, which might explain the preference of the tetrel
      atoms for the latter site.

PMID- 14577805
TI  - Organometallic chemistry of azuliporphyrins: synthesis, spectroscopy,
      electrochemistry, and structural characterization of nickel(II), palladium(II),
      and platinum(II) complexes of azuliporphyrins.
AB  - Four azuliporphyrins, two meso-unsubstituted and two meso-tetraaryl substituted,
      were investigated in the synthesis of novel organometallic compounds. The meso
      unsubstituted or "etio" series azuliporphyrins 8 reacted with nickel(II) acetate,
      palladium(II) acetate, and platinum(II) chloride in DMF to give the corresponding
      chelates 14-16, where the metal cation lies within the macrocyclic cavity and
      binds to all three nitrogens and the internal carbon atom. The newly available
      meso-tetraarylazuliporphyrins 13 similarly afforded the corresponding nickel(II),
      palladium(II), and platinum(II) complexes, 17-19, respectively. The new
      organometallic complexes are stable nonpolar compounds and were fully
      characterized spectroscopically and by mass spectrometry. The UV-vis data
      indicate that these complexes, in common with the parent azuliporphyrin system 8,
      do not possess porphyrin-type aromaticity. However, electron donation from the
      azulene unit can give rise to dipolar resonance contributors that provide a
      degree of carbaporphyrin-type aromatic character. The platinum(II)
      azuliporphyrins 16 gave noteworthy proton NMR spectra where the meso-protons
      showed satellite peaks due to transannular coupling to platinum-195. The pyrrolic
      protons of the platinum(II) meso-tetraarylazuliporphyrin 19b also showed similar
      satellite peaks due to coupling from the platinum-195 isotope. The
      electrochemistry of free base tetraphenylazuliporphyrin 13a and the related
      nickel(II) and palladium(II) complexes was investigated using cyclic voltammetry,
      and these data indicate that metal coordination improves the reversibility of the
      ligand-based oxidations. Nickel(II) azuliporphyrin 14a and palladium(II)
      tetrakis(4-chlorophenyl)azuliporphyrin 18b were also structurally characterized
      by X-ray crystallography. The macrocyclic core of the palladium(II) complex 18b
      was significantly more planar than the nickel(II) derivative 14b, and this
      difference was attributed to the better size match between the azuliporphyrin
      cavity and the larger palladium(II) ion. The straightforward synthesis of
      metalloazuliporphyrins under mild conditions, and their interesting
      spectroscopic, electrochemical, and structural features, demonstrates that the
      azuliporphyrin system holds great promise as a platform for organometallic
      chemistry.

PMID- 14577807
TI  - "Phonological development of toddlers with unilateral cleft lip and palate who
      were treated with and without infant orthopedics: a randomized clinical trial",
      by Konst E M, et al.

PMID- 14577808
TI  - Orthopedically induced condylar growth in a patient with hemifacial microsomia.
AB  - OBJECTIVE: Hemifacial microsomia is a congenital abnormality that causes three
      dimensional facial asymmetry, affection of the dental occlusion, and failure of
      growth of the midface in the growing child. This report outlines orthopedically
      induced condylar growth in a patient with hemifacial microsomia. PATIENT: A 7
      year-old girl with hemifacial microsomia, complete absence of the left mandibular
      condyle, and severe facial asymmetry was treated orthopedically in an early stage
      by means of a functional appliance. Functional therapy was instituted to stretch
      the deficient soft tissues to guide and promote skeletal growth and stimulate the
      affected areas. The treatment was completed with fixed appliances. RESULTS: The
      effect of the therapy was an excessive change in condylar growth in the affected
      side. Facial asymmetry was corrected and a symmetric mouth opening was
      established. CONCLUSIONS: The treatment of patients with hemifacial microsomia
      should be initiated early enough so that the stimulus could in some degree
      normalize the deficient tissues and induce bone apposition, and in some cases
      surgical intervention could be avoided.

PMID- 14577809
TI  - Treatment of an infant with a rare cleft resolved with use of an orthopedic
      appliance.
AB  - OBJECTIVE: Cases of bilateral complete clefts of the primary palate and
      unaffected secondary palate are very rare. One of these cases as well as a new
      method of presurgical orthopedics to solve the protruding premaxilla protrusion
      is presented.

PMID- 14577810
TI  - Congenital common cavity deformity of frontal, ethmoid, and sphenoid sinuses.
AB  - OBJECTIVE: To present a 17-year-old adolescent patient with lost right eye visual
      field and intermittent headache since the age of 14 years. The cranium was
      prominent at the right frontal region. The patient had no history of head trauma
      or infection and his past medical story was unremarkable. His mental status was
      normal. Computed tomography scanning revealed an abnormal occurrence of a common
      cavity deformity of the frontal, ethmoid, and sphenoid sinuses. No other lesions
      or deformities were present. Such common cavity deformity of these paranasal
      sinuses has not previously been reported in the English literature.

PMID- 14577811
TI  - A missense mutation in the SH3BP2 gene on chromosome 4p16.3 found in a case of
      nonfamilial cherubism.
AB  - OBJECTIVE: Cherubism is a rare hereditary multilocular cystic disease of the
      jaws, characterized by its typical appearance. Although nonfamilial cases have
      been reported, it is difficult to distinguish nonfamilial cherubism from central
      giant cell granuloma. Recent studies have revealed the point mutations in the
      SH3BP2 gene on chromosome 4p16.3 in cherubism families. In this article, the
      SH3BP2 gene in nonfamilial cherubism was examined. PATIENT: A 21-year-old
      Japanese woman with nonfamilial cherubism. INTERVENTIONS: Genomic DNA was
      purified from a blood sample obtained from the patient and used for direct
      sequencing. In addition, a sample of the lesion, resected during surgery, was
      used for histologic and immunohistochemical purposes. RESULTS: Genomic DNA
      sequencing found a Pro418Arg mutation in the SH3BP2 gene of the patient. In a
      histochemical analysis, the multinucleated giant cells proved to be strongly
      positive for PGM-1, KP-1, and tartrate-resistant acid phosphatase and faintly
      positive for osteopontin. CONCLUSIONS: The missense mutation Pro418Arg was
      identified in the SH3BP2 gene from a nonfamilial case of cherubism. DNA diagnosis
      may play a significant role in the identification of cherubism.

PMID- 14577812
TI  - Cleft palate repair in spondyloepiphyseal dysplasia congenita: minimizing the
      risk of cervical cord compression.
AB  - OBJECTIVE: Spondyloepiphyseal dysplasia congenita (SEDC) is a rare, inheritable
      condition that can include dwarfism, cleft palate, and C(1-2) instability. When
      repairing a cleft palate in a patient with SEDC, there is a significant risk of
      cord compression at the C(1-2) level because of neck hyperextension required for
      the operation. This reports presents a patient with SEDC who underwent surgery
      for a cleft palate, using a Ferno vacuum splint to immobilize the spine.
      INTERVENTION: The patient underwent general anesthesia. Good access was gained to
      the palate, and it was repaired without any complications. Particular attention
      was paid to maintaining the neck in a neutral position. CONCLUSIONS: The
      described technique provides the patient with the safest possible situation
      during anesthesia for cleft palate repair.

PMID- 14577813
TI  - Maternal drug use and infant cleft lip/palate with special reference to
      corticoids.
AB  - OBJECTIVE: To study the association between maternal drug use in early pregnancy
      and orofacial cleft in the infant. DESIGN: Register analysis based on
      prospectively collected information. PATIENTS: All delivered women in Sweden July
      1, 1995, through December 31, 2001. MAIN OUTCOME MEASURE: Presence of orofacial
      cleft in infant. RESULTS: Prospective information on maternal drug use during the
      first trimester, as reported in early pregnancy, was studied in 1142 infants with
      orofacial clefts, isolated or with other malformations, excluding chromosome
      anomalies. Any drug use was not associated with clefts (odds ratio [OR] = 0.98,
      95% confidence interval [95% CI] = 0.85 to 1.13), with isolated clefts (OR =
      0.92) with isolated median cleft palate (OR = 1.03, 95% CI = 0.79 to 1.36) or
      with isolated cleft lip with or without cleft palate (OR = 0.86, 95% CI = 0.71 to
      1.05). Reported use of multivitamins, folic acid, or B(12) was not associated
      with a decrease in orofacial cleft risk (OR = 1.00, 95% CI = 0.63 to 1.52). ORs
      above 2 were seen for some drugs: sulfasalazine, naproxen, and anticonvulsants,
      but only a few exposed cases occurred. An association between glucocorticoid use
      and infant cleft was indicated and seemed to be strongest for median cleft
      palate. CONCLUSION: Maternal drug use seems to play only a small role for the
      origin of orofacial clefts, at least in Sweden.

PMID- 14577814
TI  - Nasopharyngoscopy in Robin sequence: clinical and predictive value.
AB  - OBJECTIVE: To correlate nasopharyngoscopic findings with clinical manifestations
      during the first month of life and study the course of respiratory obstruction
      during the first year in infants with Robin sequence (RS). DESIGN: A longitudinal
      prospective study of children with RS. SETTING: Hospital de Reabilitacao de
      Anomalias Craniofaciais, University of Sao Paulo, Bauru-SP, Brazil, 1998 to 2000.
      PATIENTS: Fifty-six children were studied from the age of 1 month to 12 months.
      INTERVENTIONS: The type of respiratory obstruction was defined by
      nasopharyngoscopy. Patients for whom glossoptosis was the only mechanism of
      respiratory obstruction were classified as having mild, moderate, or severe
      glossoptosis by nasopharyngoscopy and as mild, moderate, or severe cases with
      respect to the clinical manifestations. RESULTS: Forty-two (75%) patients showed
      respiratory obstruction caused by glossoptosis; seven (43.7%) of these infants
      with mild clinical manifestations showed moderate glossoptosis during the first
      month of life and five (31.3%) presented severe glossoptosis; 10 (45.5%) of the
      infants with severe clinical manifestations showed moderate and 11 (50.0%) severe
      glossoptosis. At 12 months of age, glossoptosis was mild or absent in 83.3% of
      the patients, moderate in 14.3% and severe in 2.4%. CONCLUSIONS: A poor
      correlation between the severity of glossoptosis and the severity of clinical
      manifestations was observed for patients with respiratory obstruction caused by
      glossoptosis during the first month of life, but the correlation between
      glossoptosis and respiratory distress according to age was statistically
      significant. Nasopharyngoscopy is not a good method for predicting the severity
      of the clinical course of respiratory obstruction caused by glossoptosis.

PMID- 14577815
TI  - Velopharyngeal morphology of patients with persistent velopharyngeal incompetence
      following repushback surgery for cleft palate.
AB  - OBJECTIVE: To characterize the velopharyngeal morphology of patients with
      persistent velopharyngeal incompetence (VPI) following repushback surgery for
      cleft palate. PARTICIPANTS: Seven patients with moderate to severe VPI following
      repushback surgery for secondary correction of cleft palate, and 14 patients who
      had already obtained complete velopharyngeal closure function (VPF) were
      enrolled. Control data were obtained from the longitudinal files of 20 normal
      children in Kyushu University Dental Hospital. MAIN OUTCOME MEASURES: Skeletal
      landmarks and measurements were derived from tracing of lateral roentgenographic
      cephalograms. The measurements included velar length, pharyngeal depth, and
      pharyngeal height and the ratio of velar length to pharyngeal depth.
      Additionally, the configuration of the upper pharynx (pharyngeal triangle)
      involving the cranial base, cervical vertebrae, and the posterior maxilla and
      also the position of posterior pharyngeal wall (PPW) in the pharyngeal triangle
      were analyzed. RESULTS: The VPI group had a significantly shorter velar length
      and greater pharyngeal depth, resulting in a smaller length/depth ratio than the
      controls. The points of PPW and cervical vertebrae of the VPI group were located
      more posteriorly and inferiorly than those in the group with complete VPF after
      the primary operation and the controls. The positions of cranial base and maxilla
      were not significantly different. Additionally, the position of PPW in the
      pharyngeal triangle was located significantly posteriorly and superiorly in the
      VPI group, compared with the controls. CONCLUSIONS: The craniopharyngeal
      morphology of patients with persistent VPI was characterized by a short palate,
      wide-based and counterclockwise-rotated pharyngeal triangle, and posteriorly and
      superiorly positioned PPW. These might be contributory factors for the prediction
      of VPF before repushback surgery for cleft palate.

PMID- 14577816
TI  - Development of the orohypopharyngeal cavity in normal infants and young children.
AB  - OBJECTIVE: To study the growth of the oropharynx and hypopharynx in infants and
      young children by measuring the lengths of the segments between nasopharyngeal
      valve and tongue base, tongue base and arytenoids, and arytenoids and upper
      esophageal sphincter. These measurements will be used as references for
      developing manofluoroscopy to study deglutition in infants and young children.
      PATIENTS AND METHODS: Twenty-three children (14 boys, 9 girls) between birth and
      4 years of age were prospectively studied. All children had near normal growth
      parameters and were free of medical illnesses or other major medical conditions
      that are known to influence the pharyngeal cavity. Lateral videofluoroscopy was
      used to assess the pharyngeal structures during breathing. All images were
      digitally recorded and analyzed using a computer program designed specifically
      for this study. RESULTS AND CONCLUSIONS: Statistically significant correlations
      were found between the age or height of the patient and the distance from
      velopharyngeal valve to tongue base and the distance from tongue base to
      arytenoids, showing a linear increase of the length of the oro- and hypopharynx
      with age and patient height. There was no significant difference in the
      pharyngeal distances between boys and girls. On the basis of these results, a
      linear regression comparison could be established to define the length of each
      pharyngeal segment for any age until 4 years and for the 50th percentile of
      height.

PMID- 14577817
TI  - Use of a perceptual evaluation instrument to assess the effects of infant
      orthopedics on the speech of toddlers with cleft lip and palate.
AB  - OBJECTIVE: To investigate the effects of infant orthopedics (IO) administered in
      the first year of life on the speech characteristics of 2.5-year-old children
      with complete unilateral cleft lip and palate (UCLP) using a perceptual
      evaluation instrument with equal-appearing interval (EAI) scales. DESIGN: In a
      prospective randomized clinical trial (Dutchcleft), two groups of children with
      complete UCLP were followed longitudinally. One group received IO based on a
      modified Zurich approach (IO group), and the other group did not (non-IO group).
      The appliance was used until soft palate closure at age 12 months. Hard palate
      closure is delayed until 9 years of age. PARTICIPANTS: Three groups of 2.5-year
      old toddlers participated in this investigation: 10 IO, 10 non-IO, and 8 noncleft
      controls matched for age and socioeconomic status. METHOD: Five trained listeners
      assessed the children's speech in a blinded perceptual rating procedure. They
      judged 13 specific speech characteristics and indicated their total impression of
      speech on EAI scales. RESULTS: The reliability and consistency of 11 of the
      rating scales was good. The intelligibility rating scale was the single speech
      characteristic that distinguished the IO group from the non-IO group; the IO
      group was judged to be superior. The cleft groups differed from the noncleft
      group on 9 of the 11 scales. CONCLUSIONS: Evaluation of speech by means of the
      present newly developed perceptual rating instrument showed that the IO group
      obtained significantly higher ratings for intelligibility than the non-IO group.
      The groups did not differ regarding any of the other speech aspects.

PMID- 14577818
TI  - The relationship between the characteristics of speech and velopharyngeal gap
      size.
AB  - OBJECTIVE: The purpose of this study was to examine the relationship between
      perceptual characteristics of hypernasality, nasal emission and nasal rustle, and
      size of the velopharyngeal gap. DESIGN: A retrospective medical chart review.
      SETTING: Cincinnati Children's Hospital Medical Center. SUBJECTS: Subjects were
      patients of the Craniofacial Anomaly Team. All were between ages 3 and 12 years
      and diagnosed with velopharyngeal dysfunction secondary to cleft palate +/- cleft
      lip. A total of 173 charts were reviewed. OUTCOME MEASURES: Speech
      characteristics were assessed perceptually by an experienced speech-language
      pathologist. Following that assessment, velopharyngeal closure was evaluated
      using videofluoroscopy, nasopharyngoscopy, or both. RESULTS: Based on the
      perceptual ratings alone, 21 subjects were diagnosed with nasal rustle only, 27
      had hypernasality with nasal rustle, 89 had hypernasality with nasal emission
      without nasal rustle, and 36 had hypernasality with no audible nasal emission. An
      ordinal logit regression was conducted and showed that moderate and severe
      hypernasality contributed significantly to the prediction of a large gap size;
      nasal rustle contributed significantly to prediction of a small gap size.
      Perceptual characteristics of speech correctly predicted gap size for 121 of the
      173 subjects (70%). CONCLUSIONS: This investigation revealed that some
      information regarding velopharyngeal gap size may be predicted from the speech
      assessment alone. Confidence in the prediction is strongest if the patient has
      nasal rustle, suggesting a small gap, or if the patient has moderate to severe
      hypernasality, which is more commonly associated with a large opening.

PMID- 14577819
TI  - Clinical and microbiological evaluation of the periodontal status of children
      with unilateral complete cleft lip and palate.
AB  - OBJECTIVE: To compare periodontal conditions in children with and without cleft.
      DESIGN: Clinical examinations and microbiological analysis of 57 selected
      children, including 30 with unilateral complete cleft lip and palate
      (experimental group) and 27 without clefts (control group). SETTING: Hospital of
      Rehabilitation of Craniofacial Anomalies (HRCA) in Bauru, Sao Paulo, Brazil.
      PATIENTS, PARTICIPANTS: All children examined were healthy and between the ages
      of 5 and 6 years. RESULTS: The mean plaque index (PI) in the experimental group
      was higher (1.82 +/- 0.3) than in the control group (1.63 +/- 0.38), although
      this difference was not statistically significant. The mean gingival index (GI)
      in the experimental group (1.82 +/- 0.38) was found to be significantly higher (p
      <.05) than that of the control group (0.79 +/- 0.33). The cleft area in the
      experimental group, with a mean PI of 2.04 +/- 0.58 and mean GI of 1.11 +/- 0.26,
      compared with the posterior area, with a mean PI of 1.74 +/- 0.37 and mean GI of
      1.04 +/- 0.26, showed a statistically significant difference only in the PI. Most
      of the children in both experimental and control groups presented a moderate PI
      degree (73.33% and 81.48%, respectively) and a high prevalence of mild gingivitis
      (53.33% and 70.37%, respectively). Analysis of the organisms showed that
      Prevotella nigrescens was detected in 16.67% of the experimental group and 11.11%
      of the control, whereas Porphyromonas gingivalis and Treponema denticola were not
      detected. CONCLUSION: Children with clefts showed greater gingival inflammation,
      despite the same amount of plaque and prevalence of microorganisms.

PMID- 14577820
TI  - Three-dimensional morphology of the palate in subjects with isolated cleft palate
      at the stage of permanent dentition.
AB  - OBJECTIVE: Three-dimensional analysis of palate size and shape in patients with
      isolated cleft palate at the stage of permanent dentition. DESIGN: Cross
      sectional study using Fourier transform profilometry. SUBJECTS: Twenty-nine
      randomly selected dental casts of approximately 15-year-old boys with isolated
      cleft palate and 28 dental casts of normal boys of the same age. INTERVENTIONS:
      All patients were operated on by the same method (pushback and pharyngeal flap
      surgery) at a mean age of 4.5 years. MAIN OUTCOME MEASURES: Data on the palate
      height in 210 defined locations (pixels). RESULTS: The palate in isolated clefts
      is narrower throughout its whole extent and lower from the level of the first
      premolars. The difference, as compared with controls, increases in a posterior
      direction. At the level of the first molars, palatal height is reduced by one
      quarter, the area of the transversal section by more than one-third. The shaping
      of the palate vault is, on average, symmetrical with a marked interindividual
      variability. Palatal height does not depend on the width of the dentoalveolar
      arch, and the height of the primary palate is not reduced. CONCLUSION: The
      smaller width and reduced height from the level of the first premolars
      posteriorly confirm the substantially reduced space available for the tongue in
      patients with isolated cleft palate. Deviations are on the average symmetrical,
      and the anterior part of the palate is not shallower.

PMID- 14577821
TI  - Longitudinal evaluation of secondary bone grafting into the alveolar cleft.
AB  - OBJECTIVE: To longitudinally evaluate the outcome of secondary bone grafting
      (SBG) using computed tomograms (CTs) and conventional dental radiographs.
      SUBJECTS: Nineteen alveolar clefts from 17 patients were used in this study.
      METHOD: A two-dimensional evaluation of SBG was performed using dental
      radiographs at 1 year after SBG by assigning scores of 1 to 4 (from very good to
      poor) based on postoperative marginal bone level on the alveolar side. On the
      basis of postoperative marginal bone levels on the nasal side, clefts were also
      assigned to groups with the bony bridge on or above (group I) or below (group II)
      a horizontal reference line. Three-dimensional evaluation of the SBG was
      performed on horizontal CT slices with the residual cortical bone (RCB) ratio
      before SBG (T0) as well as 1.5 (T1), 3 (T2), 6 (T3), and 12 months (T4) after
      SBG. RESULTS: The RCB ratio at T4 in the group with scores 1 and 2 was
      significantly smaller than that of score 3. Furthermore, the mean RCB ratio at T4
      in group I was significantly smaller than that in group II. Nineteen alveolar
      clefts were divided into two groups, A and B, based on a cluster analysis of the
      RCB ratios. Group A showed a continuous decrease in the RCB ratio from T0 to T2,
      but group B showed a significant decrease only in the period from T0 to T1.
      CONCLUSION: These results suggested that the RCB ratio might be a useful
      parameter for evaluation of the bony bridge after SBG.

PMID- 14577822
TI  - Alternative impression technique for a speech-aid prosthesis.
AB  - OBJECTIVE: Prosthetic treatment for speech disorders attributable to surgically
      acquired soft palate defects are introduced. CASE: A patient who underwent soft
      palate resection for cancer is presented. The resected portion of the soft palate
      was confined to the posterior segments. A prosthesis with a speech bulb was
      adapted to the patient. CONCLUSION: Excellent restoration of speech and
      improvement of velopharyngeal function was achieved following placement of the
      special prosthesis.

PMID- 14577823
TI  - Segment distraction to reduce a wide alveolar cleft before alveolar bone
      grafting.
AB  - OBJECTIVE: To demonstrate a method for reduction of wide alveolar clefts prior to
      bone grafting. This method aims to facilitate bone grafting and achieve adequate
      soft tissue coverage of the graft with attached gingiva. CASE REPORT: Treatment
      of a patient with bilateral cleft lip and palate with a severe alveolar defect on
      the left side is illustrated. Distraction osteogenesis was used to mesialize the
      left segment so that the alveolar cleft was reduced to a minimum. After a 10-week
      retention period, bone grafting of the reduced alveolar defect was successfully
      performed. After consolidation of the bone graft, the alveolar cleft was found to
      have an osseous closure with adequate soft tissue coverage. CONCLUSION: In
      patients with a wide alveolar cleft, soft tissue coverage with keratinized mucosa
      can be more readily assured by reducing the alveolar cleft by callus distraction
      to mesialize the lateral segment prior to bone grafting.

PMID- 14577824
TI  - The quest for certainty: goodbye to index cards.

PMID- 14577825
TI  - Impact of explicit information on implicit motor-sequence learning following
      middle cerebral artery stroke.
AB  - BACKGROUND AND PURPOSE: Recovery of motor skills following stroke is supported,
      in part, by the implicit memory system. However, attempts to guide learning
      commonly use explicit instructions concerning "how to" perform a movement task.
      The purpose of this work was to systematically investigate the impact of explicit
      information (EI) on implicit motor-sequence learning using the ipsilesional arm
      in people with damage in the middle cerebral artery (MCA) distribution. SUBJECTS
      AND METHODS: Ten people with unilateral stroke in the MCA distribution affecting
      the sensorimotor cortical areas and 10 people with no known pathology or
      impairment (control participants) were randomly divided into 2 groups. One group
      was provided with EI and one group was not (EI and No-EI groups, respectively) as
      the participants practiced an implicit motor-sequencing task over 3 days, with a
      retention test on day 4. RESULTS: A 3-way interaction demonstrated that, across
      days of practice, EI had opposite effects on implicit motor-sequence performance
      for the 2 groups. Post hoc tests confirmed that EI facilitated the performance of
      the control participants in the EI group but interfered with the performance of
      the participants with stroke in the EI group. This interference effect persisted,
      and was evident during the retention test in the participants with stroke in the
      EI group. DISCUSSION AND CONCLUSION: Explicit information was detrimental for
      implicit motor-sequence learning following MCA stroke. Rehabilitation outcomes
      may benefit from consideration of stroke location when determining the degree to
      which EI can augment implicit motor skill learning.

PMID- 14577827
TI  - Pediatric constraint-induced movement therapy for a young child with cerebral
      palsy: two episodes of care.
AB  - BACKGROUND AND PURPOSE: This case report describes the use of "Pediatric
      Constraint-Induced Therapy (Pediatric CI Therapy)" given on 2 separate occasions
      for a young child with quadriparetic cerebral palsy. CASE DESCRIPTION: The child
      was 15 months of age at the beginning of the first episode of care. She had
      previously received weekly physical therapy and occupational therapy for 11
      months, but she had no functional use of her right upper extremity (UE),
      independently or in an assistive manner. She scored from 5 to 7 months below her
      chronological age on developmental assessments in gross motor, fine motor, and
      self-help skills. INTERVENTION: Pediatric CI Therapy involved placement of a full
      arm, bivalved cast on the child's less affected UE while providing 3 weeks of
      intensive intervention (6 hours a day) for the child's more affected UE
      (intervention 1). Therapy included activities that were goal oriented but broken
      down into progressively more challenging step-by-step tasks. Pediatric CI Therapy
      was administered again 5 months later to promote UE skills and independence
      (intervention 2). OUTCOMES: The child developed new behaviors throughout both
      interventions. During intervention 1, the child developed independent reach,
      grasp, release, weight bearing (positioned prone on elbows) of both UEs,
      gestures, self-feeding, sitting, and increased interactive play using both UEs.
      During intervention 2, she had increased independence and improved quality of UE
      movement, as supported by blinded clinical evaluations and parent ratings.

PMID- 14577826
TI  - Using clinical outcomes to identify expert physical therapists.
AB  - BACKGROUND AND PURPOSE: Previous studies of expert physical therapists have
      sampled therapists based on years of clinical experience or reputation, not on
      their patients' clinical outcomes. The purposes of this study were to identify
      expert physical therapists by using patient self-reported outcomes and to
      describe the characteristics of clinicians whose patients with lumbar spine
      syndromes reported higher health-related quality of life (HRQL) following
      rehabilitation. METHODS: Retrospective data were analyzed on 24276 patients (mean
      age=47.8 years, SD=16, range=14-97) with lumbar spine syndromes treated by 930
      physical therapists participating in the Focus On Therapeutic Outcomes database
      in 1999-2000. Physical therapists and staff answered questions concerning years
      of experience and practice setting when starting their participation in the
      outcomes system. Patient self-report HRQL data were collected at intake and
      discharge from outpatient rehabilitation. Discharge HRQL data were risk adjusted
      using patient characteristics. Data were aggregated by physical therapist. Risk
      adjusted discharge HRQL scores were used to classify physical therapists whose
      patients reported mean HRQL improvement above the 90th percentile as experts and
      physical therapists whose patients reported mean HRQL improvement between the
      45th and 55th percentiles as average. RESULTS: Therapists classified as expert
      had fewer patients in the database than did therapists classified as average
      (mean SD) (19 +/-17 versus 29 +/-22). Mean treatment duration was different
      between groups (32 +/- 11 days for the expert group versus 31+/-8 days for the
      average group). DISCUSSION AND CONCLUSION: The results challenge assumptions that
      extensive clinical experience is necessary to achieve superior patient outcomes,
      and they provide information about the relationship between therapist
      characteristics and patient outcomes.

PMID- 14577828
TI  - One grip a little stronger.

PMID- 14577829
TI  - Making vision 2020 a reality.

PMID- 14577830
TI  - Distribution and elimination of crystalloid fluid in pre-eclampsia.
AB  - Pre-eclampsia (PE) is a disease of pregnancy associated with peripheral oedema
      and hypovolaemia, but few details are known about how women with PE handle a
      volume load of crystalloid fluid compared with healthy pregnant women. To study
      this issue, Ringer's acetate solution (12.5 ml/kg of body weight) was given by
      intravenous infusion over 30 min to eight women with PE and to eight healthy
      pregnant women matched with respect to gestational week (mean, 34 weeks). Venous
      blood was sampled and excreted urine was collected over 90 min to study the time
      course of the volume expansion by means of volume kinetic analysis. The results
      show that the size of the central body fluid space expanded by the infused fluid
      was smaller in PE (mean, 2940 ml compared with 4240 ml respectively; P<0.04), and
      the clearance constants for distribution (100 ml/min compared with 43 ml/min;
      P<0.04) and elimination (125 ml/min compared with 36 ml/min; P<0.02) were higher
      in the women with PE than in the controls. Less excess volume accumulated in the
      central body fluid space in the presence of PE, whereas the rates of distribution
      and elimination were higher during and for 15 min after the infusion. It is
      concluded that Ringer's acetate solution fluid is both distributed and eliminated
      faster in women with PE than in matched pregnant controls.

PMID- 14577832
TI  - Mitogen-activated protein kinases in normal and (pre)neoplastic ovarian surface
      epithelium.
AB  - Mitogen-activated protein kinases (MAPKs) are a group of serine/threonine kinases
      which are activated in response to a diverse array of extracellular stimuli and
      mediate signal transduction from the cell surface to the nucleus. It has been
      demonstrated that MAPKs are activated by external stimuli including
      chemotherapeutic agents, growth factors and reproductive hormones in ovarian
      surface epithelial cells. Thus, the MAPK signaling pathway may play an important
      role in the regulation of proliferation, survival and apoptosis in response to
      these external stimuli in ovarian cancer. In this article, an activation of the
      MAPK signaling cascade by several key reproductive hormones and growth factors in
      epithelial ovarian cancer is reviewed.

PMID- 14577831
TI  - Estrogen, progesterone and epithelial ovarian cancer.
AB  - Ovarian carcinoma (OCa) continues to be the leading cause of death due to
      gynecologic malignancies and the vast majority of OCa is derived from the ovarian
      surface epithelium (OSE) and its cystic derivatives. Epidemiological evidence
      strongly suggests that steroid hormones, primarily estrogens and progesterone,
      are implicated in ovarian carcinogenesis. However, it has proved difficult to
      fully understand their mechanisms of action on the tumorigenic process. New
      convincing data have indicated that estrogens favor neoplastic transformation of
      the OSE while progesterone offers protection against OCa development.
      Specifically, estrogens, particularly those present in ovulatory follicles, are
      both genotoxic and mitogenic to OSE cells. In contrast, pregnancy-equivalent
      levels progesterone are highly effective as apoptosis inducers for OSE and OCa
      cells. In this regard, high-dose progestin may exert an exfoliation effect and
      rid an aged OSE of pre-malignant cells. A limited number of clinical studies has
      demonstrated efficacies of antiestrogens, aromatase inhibitors, and progestins
      alone or in combination with chemotherapeutic drugs in the treatment of OCa. As a
      result of increased life expectancy in most countries, the number of women taking
      hormone replacement therapies (HRT) continues to grow. Thus, knowledge of the
      mechanism of action of steroid hormones on the OSE and OCa is of paramount
      significance to HRT risk assessment and to the development of novel therapies for
      the prevention and treatment of OCa.

PMID- 14577833
TI  - Early events in ovarian oncogenesis.
AB  - Ovarian cancer represents the most lethal of the gynecological neoplasms. The
      molecular and genetic events associated with early ovarian oncogenesis are still
      largely unknown, thus contributing to the lack of reliable biomarkers for disease
      detection. Since the majority of ovarian tumors are diagnosed at an advanced
      stage, the availability of early ovarian cancer tissue samples for molecular
      analyses is very limited. In this review, problems encountered in the study of
      early ovarian cancer are presented, along with the controversies concerning
      precursor lesions and stepwise progression towards ovarian malignancy.
      Experimental modeling in the development of ovarian cancer is also described, as
      well as genetic and epigenetic alterations associated with early ovarian cancer.
      Lastly, examples of technological advances in the study of early ovarian cancer
      are discussed. Hopefully, the increasing knowledge about molecular and genetic
      events involved in the early stages of ovarian tumorigenesis will provide the
      basis for management of ovarian cancer in the future.

PMID- 14577834
TI  - Cardiac Tamponade Secondary to Metastasis from Adenocarcinoma of the Parotid
      Gland.
AB  - BACKGROUND: Metastatic involvement of pericardium producing cardiac tamponade is
      rare. When occurs it is mainly from the lung, breast and the neoplasms of the
      lymphoreticular system. Hematogenous spread of parotid adenocarcinoma to heart is
      extremely rare and only two cases have been reported in literature so far. CASE
      PRESENTATION: We report an unusual case of a patient with adenocarcinoma of the
      parotid gland, which presented with cardiac tamponade and was treated urgently
      with pericardial drainage and intrapericardial injection of cisplatin.
      CONCLUSIONS: Our case demonstrates the possibility of metastatic pericardial
      involvement and cardiac tamponade in patients with parotid adenocarcinoma. The
      patient was successfully treated with pericardial drainage and intrapericardial
      injection of chemotherapeutic agent to control recurrent pericardial effusion.

PMID- 14577835
TI  - Functional status of persons with chronic fatigue syndrome in the Wichita,
      Kansas, population.
AB  - BACKGROUND: Scant research has adequately addressed the impact of chronic fatigue
      syndrome on patients' daily activities and quality of life. Enumerating specific
      problems related to quality of life in chronic fatigue syndrome patients can help
      us to better understand and manage this illness. This study addresses issues of
      functional status in persons with chronic fatigue syndrome and other fatiguing
      illnesses in a population based sample, which can be generalized to all persons
      with chronic fatigue. METHODS: We conducted a random telephone survey in Wichita,
      Kansas to identify persons with chronic fatigue syndrome and other fatiguing
      illnesses. Respondents reporting severe fatigue of at least 1 month's duration
      and randomly selected non-fatigued respondents were asked to participate in a
      detailed telephone interview. Participants were asked about symptoms, medical and
      psychiatric illnesses, and about physical, social, and recreational functioning.
      Those meeting the 1994 chronic fatigue syndrome case definition, as determined on
      the basis of their telephone responses, were invited for clinical evaluation to
      confirm a diagnosis of chronic fatigue syndrome. For this analysis, we evaluated
      unemployment due to fatigue, number of hours per week spent on work, chores, and
      other activities (currently and prior to the onset of fatigue), and energy level.
      RESULTS: There was no difference between persons with chronic fatigue syndrome
      and persons with a chronic fatigue syndrome-like illness that could be explained
      by a medical or psychiatric condition for any of the outcomes we measured except
      for unemployment due to fatigue (15% vs. 40%, P <.01). Persons with chronic
      fatigue syndrome and other fatiguing illnesses had substantially less energy and
      spent less time on hobbies, schooling, or volunteer work than did non-fatigued
      controls (P <.01). CONCLUSIONS: Persons with chronic fatigue syndrome are as
      impaired as persons whose fatigue could be explained by a medical or psychiatric
      condition, and they have less energy than non-fatigued controls.

PMID- 14577836
TI  - Microarray analysis of gene expression during the cell cycle.
AB  - Microarrays have been applied to the determination of genome-wide expression
      patterns during the cell cycle of a number of different cells. Both eukaryotic
      and prokaryotic cells have been studied using whole-culture and selective
      synchronization methods. The published microarray data on yeast, mammalian, and
      bacterial cells have been uniformly interpreted as indicating that a large number
      of genes are expressed in a cell-cycle-dependent manner. These conclusions are
      reconsidered using explicit criteria for synchronization and precise criteria for
      identifying gene expression patterns during the cell cycle. The conclusions
      regarding cell-cycle-dependent gene expression based on microarray analysis are
      weakened by arguably problematic choices for synchronization methodology (e.g.,
      whole-culture methods that do not synchronize cells) and questionable statistical
      rigor for identifying cell-cycle-dependent gene expression. Because of the
      uncertainties in synchrony methodology, as well as uncertainties in microarray
      analysis, one should be somewhat skeptical of claims that there are a large
      number of genes expressed in a cell-cycle-dependent manner.

PMID- 14577837
TI  - Gender awareness among physicians--the effect of specialty and gender. A study of
      teachers at a Swedish medical school.
AB  - BACKGROUND: An important goal for medical education today is professional
      development including gender equality and awareness of gender issues. Are medical
      teachers prepared for this task? We investigated gender awareness among physician
      teachers, expressed as their attitudes towards the role of gender in professional
      relationships, and how it varied with physician gender and specialty. We discuss
      how this might be related to the gender climate and sex segregation in different
      specialties. METHOD: Questionnaires were sent to all 468 specialists in the
      clinical departments and in family medicine, who were engaged in educating
      medical students at a Swedish university. They were asked to rate, on visual
      analogue scales, the importance of physician and patient gender in consultation,
      of preceptor and student gender in clinical tutoring and of physician gender in
      other professional encounters. Differences between family physicians, surgical,
      and non-surgical hospital doctors, and between women and men were estimated by
      chi-2 tests and multivariate logistic regression analyses. RESULTS: The response
      rate was 65 %. There were differences between specialty groups in all
      investigated areas mainly due to disparities among men. The odds for a male
      family physician to assess gender important were three times higher, and for a
      male non-surgical doctor two times higher when compared to a male surgical
      doctor. Female teachers assessed gender important to a higher degree than men.
      Among women there were no significant differences between specialty groups.
      CONCLUSIONS: There was an interaction between physician teachers' gender and
      specialty as to whether they identified gender as important in professional
      relationships. Male physicians, especially from the surgical group, assessed
      gender important to a significantly lower degree than female physicians.
      Physicians' degree of gender awareness may, as one of many factors, affect
      working climate and the distribution of women and men in different specialties.
      Therefore, to improve working climate and reduce segregation we suggest efforts
      to increase gender awareness among physicians, for example educational programs
      where continuous reflections about gender attitudes are encouraged.

PMID- 14577838
TI  - Effect of simulated dawn on quality of sleep--a community-based trial.
AB  - BACKGROUND: Morning light exposure administered as simulated dawn looks a
      promising method to treat Seasonal Affective Disorder, but it may moreover help
      with resetting the inaccurate organisation of body clock functions relative to
      sleep occurring in winter among people in general. Disturbances in sleep patterns
      are common and may compromise wellbeing even in the short term. Our hypothesis
      was that simulated dawn could improve the subjective quality of sleep during
      winter. METHODS: A community-based trial with 100 volunteer subjects provided
      with dawn simulators. Study period lasted for eight weeks, and subjects used the
      dawn simulators for two weeks at a time, each subject acting as his own control
      (ABAB-design). Main outcome measure was subjective quality of sleep recorded each
      morning with Groningen Sleep Quality Scale. RESULTS: 77 subjects completed the
      trial. Quality of sleep improved while subjects were using dawn simulator-devices
      (p = 0.001). The treatment became beneficial after six days' use of dawn
      simulator, but the effect did not last after the use was ceased. CONCLUSION: Dawn
      simulation may help to improve the subjective quality of sleep, but the benefits
      are modest. Further research is needed to verify these findings and to elucidate
      the mechanism by which dawn simulation acts on the sleep-wake pattern.

PMID- 14577839
TI  - Functional profiling of mercuric reductase (mer A) genes in biofilm communities
      of a technical scale biocatalyzer.
AB  - BACKGROUND: Bacterial mercury resistance is based on enzymatic reduction of ionic
      mercury to elemental mercury and has recently been demonstrated to be applicable
      for industrial wastewater clean-up. The long-term monitoring of such biocatalyser
      systems requires a cultivation independent functional community profiling method
      targeting the key enzyme of the process, the merA gene coding for the mercuric
      reductase. We report on the development of a profiling method for merA and its
      application to monitor changes in the functional diversity of the biofilm
      community of a technical scale biocatalyzer over 8 months of on-site operation.
      RESULTS: Based on an alignment of 30 merA sequences from Gram negative bacteria,
      conserved primers were designed for amplification of merA fragments with an
      optimized PCR protocol. The resulting amplicons of approximately 280 bp were
      separated by thermogradient gelelectrophoresis (TGGE), resulting in strain
      specific fingerprints for mercury resistant Gram negative isolates with different
      merA sequences. The merA profiling of the biofilm community from a technical
      biocatalyzer showed persistence of some and loss of other inoculum strains as
      well as the appearance of new bands, resulting in an overall increase of the
      functional diversity of the biofilm community. One predominant new band of the
      merA community profile was also detected in a biocatalyzer effluent isolate,
      which was identified as Pseudomonas aeruginosa. The isolated strain showed lower
      mercury reduction rates in liquid culture than the inoculum strains but was
      apparently highly competitive in the biofilm environment of the biocatalyzer
      where moderate mercury levels were prevailing. CONCLUSIONS: The merA profiling
      technique allowed to monitor the ongoing selection for better adapted strains
      during the operation of a biocatalyzer and to direct their subsequent isolation.
      In such a way, a predominant mercury reducing Ps. aeruginosa strain was
      identified by its unique mercuric reductase gene.

PMID- 14577840
TI  - Quantitative trait loci in Anopheles gambiae controlling the encapsulation
      response against Plasmodium cynomolgi Ceylon.
AB  - BACKGROUND: Anopheles gambiae females are the world's most successful vectors of
      human malaria. However, a fraction of these mosquitoes is refractory to
      Plasmodium development. L3-5, a laboratory selected refractory strain,
      encapsulates transforming ookinetes/early oocysts of a wide variety of Plasmodium
      species. Previous studies on these mosquitoes showed that one major (Pen1) and
      two minor (Pen2, Pen3) autosomal dominant quantitative trait loci (QTLs) control
      the melanotic encapsulation response against P. cynomolgi B, a simian malaria
      originating in Malaysia. RESULTS: We have investigated the response of L3-5 to
      infection with P. cynomolgi Ceylon, a different but related parasite species, in
      crosses with the susceptible strain 4Arr. Refractoriness to this parasite is
      incompletely recessive. Infection and genotyping of F2 intercross females at
      genome-spanning microsatellite loci revealed that 3 autosomal QTLs control
      encapsulation of this species. Two loci map to the regions containing Pen2 and
      Pen3. The novel QTL maps to chromosome 3R, probably to polytene division 32 or
      33. Thus the relative contribution of any QTL to oocyst encapsulation varies with
      the species of parasite. Further, different QTLs were most readily identified in
      different F2 families. This, like the F1 data, suggests that L3-5 is not
      genetically homogeneous and that somewhat different pathways may be used to
      achieve an encapsulation response. CONCLUSION: We have shown here that different
      QTLs are involved in responses against different Plasmodium parasites.

PMID- 14577841
TI  - Telomere and ribosomal DNA repeats are chromosomal targets of the bloom syndrome
      DNA helicase.
AB  - BACKGROUND: Bloom syndrome is one of the most cancer-predisposing disorders and
      is characterized by genomic instability and a high frequency of sister chromatid
      exchange. The disorder is caused by loss of function of a 3' to 5' RecQ DNA
      helicase, BLM. The exact role of BLM in maintaining genomic integrity is not
      known but the helicase has been found to associate with several DNA repair
      complexes and some DNA replication foci. RESULTS: Chromatin immunoprecipitation
      of BLM complexes recovered telomere and ribosomal DNA repeats. The N-terminus of
      BLM, required for NB localization, is the same as the telomere association domain
      of BLM. The C-terminus is required for ribosomal DNA localization. BLM localizes
      primarily to the non-transcribed spacer region of the ribosomal DNA repeat where
      replication forks initiate. Bloom syndrome cells expressing the deletion alleles
      lacking the ribosomal DNA and telomere association domains have altered cell
      cycle populations with increased S or G2/M cells relative to normal. CONCLUSION:
      These results identify telomere and ribosomal DNA repeated sequence elements as
      chromosomal targets for the BLM DNA helicase during the S/G2 phase of the cell
      cycle. BLM is localized in nuclear bodies when it associates with telomeric
      repeats in both telomerase positive and negative cells. The BLM DNA helicase
      participates in genomic stability at ribosomal DNA repeats and telomeres.

PMID- 14577842
TI  - Mass spectrometric analysis of electrophoretically separated allergens and
      proteases in grass pollen diffusates.
AB  - BACKGROUND: Pollens are important triggers for allergic asthma and seasonal
      rhinitis, and proteases released by major allergenic pollens can injure airway
      epithelial cells in vitro. Disruption of mucosal epithelial integrity by
      proteases released by inhaled pollens could promote allergic sensitisation.
      METHODS: Pollen diffusates from Kentucky blue grass (Poa pratensis), rye grass
      (Lolium perenne) and Bermuda grass (Cynodon dactylon) were assessed for peptidase
      activity using a fluorogenic substrate, as well as by gelatin zymography.
      Following one- or two-dimensional gel electrophoresis, Coomassie-stained
      individual bands/spots were excised, subjected to tryptic digestion and analysed
      by mass spectrometry, either MALDI reflectron TOF or microcapillary liquid
      chromatography MS-MS. Database searches were used to identify allergens and other
      plant proteins in pollen diffusates. RESULTS: All pollen diffusates tested
      exhibited peptidase activity. Gelatin zymography revealed high Mr proteolytic
      activity at approximately 95,000 in all diffusates and additional proteolytic
      bands in rye and Bermuda grass diffusates, which appeared to be serine proteases
      on the basis of inhibition studies. A proteolytic band at Mr approximately 35,000
      in Bermuda grass diffusate, which corresponded to an intense band detected by
      Western blotting using a monoclonal antibody to the timothy grass (Phleum
      pratense) group 1 allergen Phl p 1, was identified by mass spectrometric analysis
      as the group 1 allergen Cyn d 1. Two-dimensional analysis similarly demonstrated
      proteolytic activity corresponding to protein spots identified as Cyn d 1.
      CONCLUSION: One- and two-dimensional electrophoretic separation, combined with
      analysis by mass spectrometry, is useful for rapid determination of the
      identities of pollen proteins. A component of the proteolytic activity in Bermuda
      grass diffusate is likely to be related to the allergen Cyn d 1.

PMID- 14577843
TI  - Endotoxemia and Gram-negative bacteremia as predictors of outcome in sepsis: a
      meta-analysis using ROC curves.
AB  - The prognostic value of the detection of endotoxin in plasma of patients with
      suspected Gram-negative sepsis is unclear despite numerous studies. Sixteen
      studies have reported endotoxemia detection and blood culture results with
      outcome data for 1937 patients with suspected Gram-negative sepsis. Comparisons
      of the fatality rates for the subgroups of patients with, respectively, either
      endotoxemia (group 3), or Gram-negative bacteremia (group 2), or both detected
      (group 1), versus the fatality rate for the subgroup of patients with these
      factors absent (group 4), were made based on summary odds ratios (and 95% CI).
      Summary odds ratios for the comparison of group 2 versus group 4 and group 3
      versus group 4 were non-significant (2.2; 0.9-5.8 and 2.0; 0.8-4.8,
      respectively). The summary odds ratio was significant for group 1 versus group 4
      (3.6; 2.1-6.3), and more so among studies in which non-Enterobacteriaceae were
      common among the Gram-negative blood culture isolates (4.8; 2.1-10.7).
      Endotoxemia, like Gram-negative bacteremia, is a weak prognostic indicator.
      Endotoxemia appears to have most prognostic significance when it is detected in
      the co-presence of Gram-negative bacteremia. The differing interpretations among
      published studies could be attributed to the variability in types of Gram
      negative bacteremia observed.

PMID- 14577844
TI  - Inhibition of LPS-responses by synthetic peptides derived from LBP associates
      with the ability of the peptides to block LBP-LPS interaction.
AB  - The ability of LPS-binding protein (LBP) to greatly potentiate cell responses to
      lipopolysaccharide (LPS) may largely contribute to LPS toxicity in sepsis. The
      study of agents with the capacity to block the interaction between LBP and LPS
      might improve the understanding of the role of LBP in Gram-negative infections as
      well as offering new therapeutic tools for septic disorders. Here we confirm the
      ability of synthetic peptides comprising the human LBP amino acid region 86-108
      to interfere with the LBP-LPS interaction. The analysis of selected alanine
      mutants of a blocking peptide corresponding to the LBP region 86-99 suggests the
      importance of peptide amphipathicity for the inhibitory activity. The potency of
      the native peptide and a selected analogue at inhibiting in vitro and in vivo LPS
      induced responses was associated with their relative activity in blocking LBP-LPS
      interaction. It was remarkable that these peptides were at least 500-fold more
      active in vivo than in vitro. Also, the inhibitory activity of peptides LBP86-99
      and LBPK95A seems to be independent of LBP concentrations, a behavior that may be
      relevant for the potential use of these peptides in septic disorders where LBP
      serum concentrations are considerably elevated.

PMID- 14577845
TI  - Role of lipopolysaccharide (LPS) in asthma and other pulmonary conditions.
AB  - Endotoxin significantly contaminates house dust and is an enhancing factor for
      asthma severity. Natural exposure to endotoxin in early life could influence
      immune development and protect from the risk of developing atopy. This article
      will focus on published data showing that home environmental contamination by
      endotoxin can participate in chronic airways diseases, in particular asthma.

PMID- 14577846
TI  - Molecular basis for lipopolysaccharide mimetic action of Taxol and flavolipin.
AB  - We previously reported that Taxol, which mimics the action of LPS on murine
      macrophages, induces signals via mouse TLR4/MD-2, but not via human TLR4/MD-2.
      Here we investigated the molecular basis for this species-specific action of
      Taxol. Expression of mouse MD-2 conferred both LPS and Taxol responsiveness on
      HEK293 cells expressing mouse TLR4, whereas expression of human MD-2 conferred
      LPS responsiveness alone, suggesting that MD-2 is responsible for the species
      specificity of Taxol responsiveness. Furthermore, mouse MD-2 mutants, in which
      Gln-22 was changed to other amino acids, showed dramatically reduced ability to
      confer Taxol responsiveness, although their ability to confer LPS responsiveness
      was not affected. These results indicated that Gln-22 of mouse MD-2 is essential
      for Taxol signaling, but not for LPS signaling. In this study, we also found that
      the TLR4/MD-2 complex, together with CD14, mediated signal transduction induced
      by flavolipin, an amino acid-containing lipid unique to Flavobacterium
      meningosepticum.

PMID- 14577847
TI  - Role of interferons in LPS hypersensitivity.
AB  - The innate immune response to Gram-negative bacteria depends mainly on the
      ability of the host to respond to the LPS component. Consequently, the state of
      LPS sensitivity at the time of infection and the numbers of invading bacteria
      (i.e. the amounts of LPS) are primary factors determining the innate responses
      provoked by Gram-negative pathogens. LPS sensitivity increases following
      treatment of mice with live or killed micro-organisms. Two types of sensitization
      have been recognized, strong, IFN-gamma-dependent and moderate IFN-gamma
      independent. IL-12 and IL-18 are intimately involved in the induction of IFN
      gamma by bacteria. We showed that Gram-negative bacteria induce IFN-gamma in mice
      also by an IFN-beta-dependent pathway that requires IL-18 and is independent of
      IL-12 signaling. This pathway is STAT4 dependent, the activation of which is
      directly linked to IFN-beta. Further, IFN-beta can be replaced by IFN-alpha.
      While different components of Gram-negative bacteria induce IL-12 and IL-18, LPS
      seems to be the only component in these bacteria capable of inducing IFN-beta.
      Therefore, the IFN-beta pathway of IFN-gamma induction, unlike the IL-12 pathway,
      proceeds only in LPS responder mice. The IFN-alpha/beta-dependent pathway is
      expected to play a role whenever IFN-alpha or IFN-beta, and IL-18 are produced
      concomitantly during infection.

PMID- 14577848
TI  - The role of STAT1 in viral sensitization to LPS.
AB  - The phenomenon of endotoxin sensitization by virus infection is well documented
      but not yet well understood. Infection by virtually any viral agent will quickly
      induce expression of type I interferons (IFN-alpha/beta), and type II IFN-gamma
      production will follow as NK cells and T cells are activated. It has been well
      established that type II IFN pretreatment can intensify the effects of endotoxin.
      We have recently demonstrated that type I IFN induction by lymphocytic
      choriomeningitis virus (LCMV) infection dramatically increases TNF-alpha
      production following LPS treatment, and that this sensitization by type I IFN is
      STAT1 dependent. Taken together these data suggest that the STAT1-mediated, MyD88
      independent, arm of the LPS signaling pathway plays an important role in
      endotoxin toxicity, and that this pathway mediates a major component of virus
      enhanced LPS sensitization.

PMID- 14577849
TI  - Activated protein C signals through the thrombin receptor PAR1 in endothelial
      cells.
AB  - The anti-inflammatory effects of activated protein C (APC) have lead to its
      recent approval for the treatment of sepsis. Although the endothelial cell
      protein C receptor (EPCR) plays a crucial role in APC's protective roles in
      septicemia, the precise signaling mechanism of the protease APC remains unclear.
      In fibroblast overexpression systems, we find that APC activates protease
      activated receptors (PAR) 1 and 2 in an EPCR-dependent manner. Human endothelial
      cells (HUVECs) express PAR1, PAR2 and EPCR. Stimulation of HUVECs with either
      APC, or specific receptor activating peptides for PAR1 or PAR2, show that all
      three agonists induce a very similar set of early response genes as assessed by
      high density microarray analysis. Only the transcript for monocyte chemo
      attractant protein-1 (MCP-1) was selectively induced by APC and the PAR1 agonist,
      but not by the PAR2 agonist. APC-mediated MAP kinase phosphorylation and gene
      induction were inhibited by cleavage blocking antibodies to PAR1, demonstrating
      that APC signals exclusively through PAR1 in endothelial cells. MCP-1 is
      protective in animal models of endotoxemia, suggesting that APC may prevent
      lethality in sepsis by inducing MCP-1 expression through EPCR-dependent
      activation of endothelial cell PAR1. These data demonstrate unexpected protective
      functions of the major thrombin receptor PAR1 in endothelial cells.

PMID- 14577850
TI  - TLR signaling at the intestinal epithelial interface.
AB  - The intestinal epithelium provides a critical interface between lumenal bacteria
      and the mucosal immune system. Whereas normal commensal flora do not trigger
      acute inflammation, pathogenic bacteria trigger a potent inflammatory response.
      Our studies emanate from the hypothesis that the intestinal epithelium is
      normally hyporesponsive to commensal pathogen-associated molecular patterns
      (PAMPs) such as LPS. Our data demonstrate that normal human colonic epithelial
      cells and lamina propria cells express low levels of TLR4 and its co-receptor MD
      2. This expression pattern is mirrored by intestinal epithelial cell (IEC) lines.
      Co-expression of TLR4 and MD-2 is necessary and sufficient for LPS responsiveness
      in IEC. Moreover, LPS sensing occurs along the basolateral membrane of polarized
      IEC in culture. Expression of MD-2 is regulated by IFN-gamma. Cloning of the MD-2
      promoter demonstrates that promoter activity is increased by IFN-gamma and
      blocked by the STAT inhibitor SOCS3. We conclude from our studies that the
      intestinal epithelium down-regulates expression of TLR4 and MD-2 and is LPS
      unresponsive. The Th1 cytokine IFN-gamma up-regulates expression of MD-2 in a
      STAT-dependent fashion. The results of our studies have important implications
      for understanding human inflammatory bowel diseases.

PMID- 14577851
TI  - Receptor cluster formation during activation by bacterial products.
AB  - The recognition of bacterial products, such as lipopolysaccharide (LPS) by the
      innate immune system lead to a strong pro-inflammatory response that can
      eventually lead to fatal sepsis syndrome in humans. Although CD14 and TLR4 have
      been identified as the key molecules involved in LPS-induced signal transduction,
      accumulating evidence indicates that multiple receptors are also involved. Our
      group has recently identified a cluster of receptors, involving heat-shock
      proteins 70 and 90, chemokine receptor 4 as well as growth differentiation factor
      5, that are formed following LPS stimulation. In addition, we present data
      demonstrating that these molecules associate with TLR4 and accumulate in membrane
      microdomains following LPS ligation. Our results suggest that the entire
      bacterial recognition is based around the recruitment of multiple signalling
      molecules, in addition to CD14 and TLRs, within the lipid rafts. We propose that
      different combinational associations of receptors within activation clusters
      determine the different responses to a variety of bacterial stimuli.

PMID- 14577852
TI  - Dynamical consequences of fast-rising, slow-decaying synapses in neuronal
      networks.
AB  - Synapses that rise quickly but have long persistence are shown to have certain
      computational advantages. They have some unique mathematical properties as well
      and in some instances can make neurons behave as if they are weakly coupled
      oscillators. This property allows us to determine their synchronization
      properties. Furthermore, slowly decaying synapses allow recurrent networks to
      maintain excitation in the absence of inputs, whereas faster decaying synapses do
      not. There is an interaction between the synaptic strength and the persistence
      that allows recurrent networks to fire at low rates if the synapses are
      sufficiently slow. Waves and localized structures are constructed in spatially
      extended networks with slowly decaying synapses.

PMID- 14577853
TI  - A universal model for spike-frequency adaptation.
AB  - Spike-frequency adaptation is a prominent feature of neural dynamics. Among other
      mechanisms, various ionic currents modulating spike generation cause this type of
      neural adaptation. Prominent examples are voltage-gated potassium currents (M
      type currents), the interplay of calcium currents and intracellular calcium
      dynamics with calcium-gated potassium channels (AHP-type currents), and the slow
      recovery from inactivation of the fast sodium current. While recent modeling
      studies have focused on the effects of specific adaptation currents, we derive a
      universal model for the firing-frequency dynamics of an adapting neuron that is
      independent of the specific adaptation process and spike generator. The model is
      completely defined by the neuron's onset f-I curve, the steady-state f-I curve,
      and the time constant of adaptation. For a specific neuron, these parameters can
      be easily determined from electrophysiological measurements without any
      pharmacological manipulations. At the same time, the simplicity of the model
      allows one to analyze mathematically how adaptation influences signal processing
      on the single-neuron level. In particular, we elucidate the specific nature of
      high-pass filter properties caused by spike-frequency adaptation. The model is
      limited to firing frequencies higher than the reciprocal adaptation time constant
      and to moderate fluctuations of the adaptation and the input current. As an
      extension of the model, we introduce a framework for combining an arbitrary spike
      generator with a generalized adaptation current.

PMID- 14577854
TI  - An adjustment to the time-rescaling method for application to short-trial spike
      train data.
AB  - It is important to validate models of neural data using appropriate goodness-of
      fit measures. Models summarizing some response features--for example, spike count
      distributions or peristimulus time histograms--can be assessed using standard
      statistical tools. Measuring the fit of a full point-process model of spike
      trains is more difficult. Recently, Barbieri, Quirk, Frank, Wilson, and Brown
      (2001) and Brown, Barbieri, Ventura, Kass, and Frank (2002) presented a method
      for rescaling time so that if an underlying description correctly describes the
      conditional intensity function of a point process, the rescaling will convert the
      process into a homogeneous Poisson process. The corresponding interevent
      intervals are exponential with mean 1 and can be transformed to be uniform; tests
      of the uniformity of the transformed intervals are thus tests of how well the
      model fits the data. When the lengths of interevent intervals are comparable to
      the length of the observation window, as can happen in common neurophysiology
      paradigms using short trials, the fact that long intervals cannot be observed
      (are censored) can cause the tests based on time rescaling to reject a correct
      model inappropriately. This article presents a simple adjustment to the time
      rescaling method to account for interval censoring, avoiding inappropriate
      rejection of acceptable models for short-trial data. We illustrate the
      adjustment's effect using both simulated data and short-trial data from monkey
      primary visual cortex.

PMID- 14577855
TI  - Characterization of subthreshold voltage fluctuations in neuronal membranes.
AB  - Synaptic noise due to intense network activity can have a significant impact on
      the electrophysiological properties of individual neurons. This is the case for
      the cerebral cortex, where ongoing activity leads to strong barrages of synaptic
      inputs, which act as the main source of synaptic noise affecting on neuronal
      dynamics. Here, we characterize the subthreshold behavior of neuronal models in
      which synaptic noise is represented by either additive or multiplicative noise,
      described by Ornstein-Uhlenbeck processes. We derive and solve the Fokker-Planck
      equation for this system, which describes the time evolution of the probability
      density function for the membrane potential. We obtain an analytic expression for
      the membrane potential distribution at steady state and compare this expression
      with the subthreshold activity obtained in Hodgkin-Huxley-type models with
      stochastic synaptic inputs. The differences between multiplicative and additive
      noise models suggest that multiplicative noise is adequate to describe the high
      conductance states similar to in vivo conditions. Because the steady-state
      membrane potential distribution is easily obtained experimentally, this approach
      provides a possible method to estimate the mean and variance of synaptic
      conductances in real neurons.

PMID- 14577856
TI  - Modeling reaching impairment after stroke using a population vector model of
      movement control that incorporates neural firing-rate variability.
AB  - The directional control of reaching after stroke was simulated by including cell
      death and firing-rate noise in a population vector model of movement control. In
      this model, cortical activity was assumed to cause the hand to move in the
      direction of a population vector, defined by a summation of responses from
      neurons with cosine directional tuning. Two types of directional error were
      analyzed: the between-target variability, defined as the standard deviation of
      the directional error across a wide range of target directions, and the within
      target variability, defined as the standard deviation of the directional error
      for many reaches to a single target. Both between- and within-target variability
      increased with increasing cell death. The increase in between-target variability
      arose because cell death caused a nonuniform distribution of preferred
      directions. The increase in within-target variability arose because the magnitude
      of the population vector decreased more quickly than its standard deviation for
      increasing cell death, provided appropriate levels of firing-rate noise were
      present. Comparisons to reaching data from 29 stroke subjects revealed similar
      increases in between- and within-target variability as clinical impairment
      severity increased. Relationships between simulated cell death and impairment
      severity were derived using the between- and within-target variability results.
      For both relationships, impairment severity increased similarly with decreasing
      percentage of surviving cells, consistent with results from previous imaging
      studies. These results demonstrate that a population vector model of movement
      control that incorporates cosine tuning, linear summation of unitary responses,
      firing-rate noise, and random cell death can account for some features of
      impaired arm movement after stroke.

PMID- 14577857
TI  - Radius margin bounds for support vector machines with the RBF kernel.
AB  - An important approach for efficient support vector machine (SVM) model selection
      is to use differentiable bounds of the leave-one-out (loo) error. Past efforts
      focused on finding tight bounds of loo (e.g., radius margin bounds, span bounds).
      However, their practical viability is still not very satisfactory. Duan, Keerthi,
      and Poo (2003) showed that radius margin bound gives good prediction for L2-SVM,
      one of the cases we look at. In this letter, through analyses about why this
      bound performs well for L2-SVM, we show that finding a bound whose minima are in
      a region with small loo values may be more important than its tightness. Based on
      this principle, we propose modified radius margin bounds for L1-SVM (the other
      case) where the original bound is applicable only to the hard-margin case. Our
      modification for L1-SVM achieves comparable performance to L2-SVM. To study
      whether L1- or L2-SVM should be used, we analyze other properties, such as their
      differentiability, number of support vectors, and number of free support vectors.
      In this aspect, L1-SVM possesses the advantage of having fewer support vectors.
      Their implementations are also different, so we discuss related issues in detail.

PMID- 14577858
TI  - Accurate on-line support vector regression.
AB  - Batch implementations of support vector regression (SVR) are inefficient when
      used in an on-line setting because they must be retrained from scratch every time
      the training set is modified. Following an incremental support vector
      classification algorithm introduced by Cauwenberghs and Poggio (2001), we have
      developed an accurate on-line support vector regression (AOSVR) that efficiently
      updates a trained SVR function whenever a sample is added to or removed from the
      training set. The updated SVR function is identical to that produced by a batch
      algorithm. Applications of AOSVR in both on-line and cross-validation scenarios
      are presented. In both scenarios, numerical experiments indicate that AOSVR is
      faster than batch SVR algorithms with both cold and warm start.

PMID- 14577859
TI  - Speeding up backpropagation using multiobjective evolutionary algorithms.
AB  - The use of backpropagation for training artificial neural networks (ANNs) is
      usually associated with a long training process. The user needs to experiment
      with a number of network architectures; with larger networks, more computational
      cost in terms of training time is required. The objective of this letter is to
      present an optimization algorithm, comprising a multiobjective evolutionary
      algorithm and a gradient-based local search. In the rest of the letter, this is
      referred to as the memetic Pareto artificial neural network algorithm for
      training ANNs. The evolutionary approach is used to train the network and
      simultaneously optimize its architecture. The result is a set of networks, with
      each network in the set attempting to optimize both the training error and the
      architecture. We also present a self-adaptive version with lower computational
      cost. We show empirically that the proposed method is capable of reducing the
      training time compared to gradient-based techniques.

PMID- 14577860
TI  - Traumatic cerebral vascular injury: the effects of concussive brain injury on the
      cerebral vasculature.
AB  - In terms of human suffering, medical expenses, and lost productivity, head injury
      is one of the major health care problems in the United States, and inadequate
      cerebral blood flow is an important contributor to mortality and morbidity after
      traumatic brain injury. Despite the importance of cerebral vascular dysfunction
      in the pathophysiology of traumatic brain injury, the effects of trauma on the
      cerebral circulation have been less well studied than the effects of trauma on
      the brain. Recent research has led to a better understanding of the physiologic,
      cellular, and molecular components and causes of traumatic cerebral vascular
      injury. A more thorough understanding of the direct and indirect effects of
      trauma on the cerebral vasculature will lead to improvements in current
      treatments of brain trauma as well as to the development of novel and, hopefully,
      more effective therapeutic strategies.

PMID- 14577861
TI  - Cerebral perfusion pressure directed therapy following traumatic brain injury and
      hypotension in swine.
AB  - There is a paucity of studies, clinical and experimental, attesting to the
      benefit of cerebral perfusion pressure (CPP) directed pressor therapy following
      traumatic brain injury (TBI). The current study evaluates this therapy in a swine
      model of TBI and hypotension. Forty-five anesthetized and ventilated swine
      received TBI followed by a 45% blood volume bleed. After 1 h, all animals were
      resuscitated with 0.9% sodium chloride equal to three times the shed blood
      volume. The experimental group (PHE) received phenylephrine to maintain CPP > 80
      mm Hg; the control group (SAL) did not. Outcomes in the first phase (n = 33) of
      the study were as follows: cerebro-venous oxygen saturation (S(cv)O(2)), cerebro
      vascular carbon dioxide reactivity (DeltaS(cv)O(2)), and brain structural damage
      (beta-amyloid precursor protein [betaAPP] immunoreactivity). In the second phase
      (n = 12) of the study, extravascular blood free water (EVBFW) was measured in the
      brain and lung. After resuscitation, intracranial and mean arterial pressures
      were >15 and >80 mm Hg, respectively, in both groups. CPP declined to 64 +/- 5 mm
      Hg in the SAL group, despite fluid supplements. CPP was maintained at >80 mm Hg
      with pressors in the PHE group. PHE animals maintained better S(cv)O(2) (p < 0.05
      at 180, 210, 240, 270, and 300 min post-TBI). At baseline, 5% CO(2) evoked a 16
      +/- 4% increase in S(cv)O(2), indicating cerebral vasodilatation and luxury
      perfusion. By 240 min, this response was absent in SAL animals and preserved in
      PHE animals (p < 0.05). Brain EVBFW was higher in SAL animals; however, lung
      EVBFW was higher in PHE animals. There was no difference in betaAPP
      immunoreactivity between the SAL and PHE groups (p > 0.05). In this swine model
      of TBI and hypotension, CPP directed pressor therapy improved brain oxygenation
      and maintained cerebro-vascular CO(2) reactivity. Brain edema was lower, but lung
      edema was greater, suggesting a higher propensity for pulmonary complications.

PMID- 14577862
TI  - Detrimental role of bradykinin B2 receptor in a murine model of diffuse brain
      injury.
AB  - Inhibition of the bradykinin B2 receptor type (B2R) has been shown to improve
      neurological outcome in models of focal traumatic brain injury. However, the
      involvement of B2R in trauma-induced diffuse injury has not yet been explored.
      This is an important point, since in humans a pattern of diffuse injury is
      commonly found in severely injured patients and has been associated with a poor
      neurological outcome and prognosis. Using the non-peptide B2R antagonist LF 16
      0687 Ms and B2R null (B2R-/-) mice, we investigated the role of B2R in a model of
      closed head trauma (CHT). LF 16-0687 Ms given 30 min after injury reduced the
      neurological deficit by 26% and the cerebral edema by 22% when evaluated 4 h
      after CHT. Neurological function after CHT was improved in B2R-/- mice compared
      to B2R+/+ mice, although there was no difference in the development of brain
      edema. Treatment with LF 16-0687 Ms and B(2)R gene deletion decreased the
      accumulation of neutrophils at 24 h after CHT (50% and 36%, respectively). In
      addition, the inducible NO synthase (iNOS) mRNA level increased markedly, and
      this was reduced by LF 16-0687 Ms. Taken together, these data support a
      detrimental role of B2R in the development of the neurological deficit and of the
      inflammatory secondary damage resulting from diffuse traumatic brain injury.
      Therefore, blockade of bradykinin B2 receptors might represent an attractive
      therapeutic approach in the pharmacological treatment of traumatic brain injury.

PMID- 14577863
TI  - Nervous tissue damage markers in cerebrospinal fluid after cervical spine
      injuries and whiplash trauma.
AB  - Clinical examination is the only tool available to assess the extent of the nerve
      tissue damage after a spinal cord injury, and it is well known that the
      reliability of classification based on clinical examination is not satisfactory,
      especially in cases with incomplete motor injuries. There is a need to evaluate
      new methods in order to improve the possibilities of classifying and
      prognosticating spinal cord injuries. Methods for assessing central nervous
      system (CNS) damage using markers in cerebrospinal fluid (CSF) have recently been
      developed. Previous studies have reported glial fibrillary acidic protein (GFAp)
      and neurofilament protein (NFL) levels in non-traumatic diseases in the central
      nervous system. The present study is the first report of GFAp and NFL levels in
      CSF after trauma to the cervical spine. Six cases with cord damage and pronounced
      neurological deficit showed significantly increased concentrations of both GFAp
      and NFL in the CSF. Patients with tetrapareses showed higher values than those
      with incomplete injuries. Three of the 17 whiplash cases had increased levels of
      NFL, but normal GFAp. Assessment of nervous tissue markers in CSF will probably
      improve possibilities to classify and prognosticate spinal cord injuries and also
      to evaluate pharmacological intervention. The increased levels of NFL in three
      whiplash cases indicate neural damage in a proportion of the cases with
      neurological deficit. Neurological examinations are presently the only tools for
      grading and prognostication of spinal cord injuries. Assessment of nervous tissue
      markers in CSF makes it possible to quantify the degree of nerve cell damage
      after different types of cervical spine injury ranging from spinal cord lesions
      to whiplash injuries.

PMID- 14577864
TI  - The delayed administration of dehydroepiandrosterone sulfate improves recovery of
      function after traumatic brain injury in rats.
AB  - The goal of the current study was to test the hypothesis that
      dehydroepiandrosterone-sulfate (DHEAS), a pro-excitatory neurosteroid, could
      facilitate recovery of function in male rats after delayed treatment following
      TBI. DHEAS has been found to play a major role in brain development and aging by
      influencing the migration of neurons, arborization of dendrites, and formation of
      new synapses. These characteristics make it suitable as a potential treatment to
      enhance neural repair in response to CNS injury. In our study, behavioral tests
      were conducted concurrently with DHEAS administration (0, 5, 10, or 20 mg/kg)
      starting seven days post-injury (PI). These assays included 10 days of Morris
      Water Maze testing (MWM; 7d PI), 10 days of Greek-Cross (GC; 21d PI), Tactile
      Adhesive Removal task (TAR; PI days: 6, 13, 20, 27, 34), and spontaneous motor
      behavior testing (SMB; PI days: 2, 4, 6, 12, 19, 26, 33). Brain-injured rats
      showed an improvement in performance in all tasks after 5, 10, or 20 mg/kg DHEAS.
      The most effective dose of DHEAS in the MWM was 10 mg/kg, while in the GC it was
      20 mg/kg, in TAR 5 mg/kg, and all doses, except for vehicle, were effective at
      reducing injury-induced SMB hyperactivity. In no task did DHEAS-treated animals
      perform worse than the injured controls. In addition, DHEAS had no significant
      effects on behavioral performance in the sham-operates. These results can be
      interpreted to demonstrate that after a 7-day delay, the chronic administration
      of DHEAS to injured rats significantly improves behavioral recovery on both
      sensorimotor and cognitive tasks.

PMID- 14577865
TI  - Soluble cell adhesion molecule L1-Fc promotes locomotor recovery in rats after
      spinal cord injury.
AB  - Previous studies suggest that the cell adhesion molecule L1 promotes neurite
      growth by neutralizing white matter associated inhibitors of axonal growth. We
      made a soluble chimeric dimer by linking mouse L1 to human Fc. This L1-Fc
      construct (40 microg/mL) markedly facilitated neurite outgrowth, as well as
      neuronal adhesion to white matter on frozen sections of spinal cord. We applied
      L1-Fc intrathecally (200 microg/mL at 0.5 microL/h) to rat spinal cords for 2
      weeks after a 25-mm weight drop contusion of the T13 spinal cord. Initial
      experiments indicated that L1-Fc is present in the spinal cord after 2 weeks of
      intrathecal infusion and significantly improved locomotor recovery by 6-12 weeks
      after injury. We then randomized 45 rats to intrathecal infusion of L1-Fc (L1),
      phosphate-buffered saline controls (PBS), and a mouse monoclonal IgM antibody
      (M1). By 12 weeks after injury, L1-treated rats recovered significantly (p <
      0.005) better locomotor function (BBB score 10.57 +/- 0.25, n = 14) than PBS
      treated rats (BBB score 9.00 +/- 0.33, n = 14) or M1-treated (BBB score 8.71 +/-
      0.16, n = 14). Only two rats of 22 treated with saline recovered weight-supported
      ambulation. Of 20 L1-Fc-treated rats, however, 18 recovered weight-supported
      walking by 12 weeks. The L1-Fc-treated rats also showed more consistent hindlimb
      contact placing than saline controls. We injected biotinylated dextran amine
      (BDA) into the motor cortices of 14 rats treated with L1-Fc to label
      corticospinal axons, comparing these with 13 rats treated with saline. In saline
      treated rats, BDA-labeled corticospinal axons often grew up to the impact edge
      and occasionally into the impact site. L1-treated rats showed longer
      corticospinal tract growth at the injury site. Three rats had BDA-labeled axons
      that extended beyond the impact center. One L1-Fc-treated rat showed axonal
      extension and synapse formation in cord distal to the injury. These results
      indicate that soluble L1-Fc promotes axonal growth and functional recovery after
      spinal cord injury. However, the limited corticospinal tract growth across the
      injury site cannot account for the observed locomotor recovery. Thus, L1 may be
      stimulating growth of other motor tracts or protecting axons and neurons. More
      studies are required to elucidate the mechanisms of L1-Fc-induced locomotor
      recovery.

PMID- 14577866
TI  - The role of excitotoxic injury in post-traumatic syringomyelia.
AB  - Fifty percent of patients with neurological deterioration from post-traumatic
      syringomyelia do not respond to treatment. Treatment failure is due in part to an
      incomplete understanding of the underlying aetiology. An animal model that mimics
      the human disease is required to investigate underlying pathophysiology and
      treatment options. A previous study was designed to mimic trauma-induced effects
      on the spinal cord that result in syringomyelia, combining an excitotoxic insult
      with kaolin-induced arachnoiditis. In this excitotoxic model, syringes were
      produced in 82% of animals. The aims of the current study were to improve the
      model to produce syringes in all animals treated, to examine the relative
      influences of excitotoxic injury and neuronal loss on syrinx formation, and to
      use magnetic resonance imaging (MRI) to examine syringes non-invasively. A
      temporal and dose profile of intraparenchymal quisqualic acid (QA) and
      subarachnoid kaolin was performed in Sprague Dawley rats. MRI was used to study
      four syrinx and six control animals. In one subgroup of animals surviving for 6
      weeks, 100% (eight of eight) developed syringes. Syrinx formation and enlargement
      occurred in a dose and time dependent manner, whilst significant neuronal loss
      was only dose dependent. Animal syrinx histology closely resembled human post
      traumatic syringomyelia. Axial T2-weighted MR images demonstrated syrinx
      presence. The results suggest that the formation of an initial cyst predisposes
      to syrinx formation in the presence of subarachnoid adhesions.

PMID- 14577867
TI  - Complement activation following optic nerve crush in the adult rat.
AB  - Activation of the complement cascade following peripheral nerve axotomy and
      following traumatic brain injury has been demonstrated in previous studies. This
      study investigates the temporal pattern of microglia/macrophages and complement
      activation following axotomy of sensory CNS neurons, using a standardized
      experimental crush injury of the optic nerve in adult rats. Numerous ED1-labeled
      macrophages were found at the lesion site and distal to the injury at 7 days post
      injury (dpi). Complement C3-mRNA was upregulated 2-28 days post lesion,
      indicating local synthesis of complement in the optic nerve. Furthermore,
      increased immunoreactivity (IR) for the end product of the complement cascade,
      the membrane attack complex (MAC), was detected along disintegrating axons co
      labeled with anti-neurofilament distal to the injury. Double-labeling for
      microglia show MAC-immunoreactivity expressed in their immediate vicinity,
      indicating a key role of microglia/macrophages in complement activation. The
      complement regulator Clusterin was upregulated in astrocytes at the lesion site
      as well as in the distal portion of the injured optic nerve, suggesting
      activation of a defense response to endogenous complement attack. A crush injury
      of the optic nerve leads to complement activation at the site of lesion and along
      the distal portion of the nerve, as well as upregulation of the complement
      inhibitor Clusterin at least in astrocytes. Reactive microglial cells seem to
      have a key role in complement activation as a local source of C3. We suggest that
      the balance between complement activation and their regulators may have impact on
      axonal degeneration following optic nerve injury.

PMID- 14577868
TI  - Neuropathology of fatal infant head injury.

PMID- 14577869
TI  - A tribute to the Columbia mission crew.

PMID- 14577870
TI  - The NASA Astrobiology Roadmap.
AB  - The NASA Astrobiology Roadmap provides guidance for research and technology
      development across the NASA enterprises that encompass the space, Earth, and
      biological sciences. The ongoing development of astrobiology roadmaps embodies
      the contributions of diverse scientists and technologists from government,
      universities, and private institutions. The Roadmap addresses three basic
      questions: How does life begin and evolve, does life exist elsewhere in the
      universe, and what is the future of life on Earth and beyond? Seven Science Goals
      outline the following key domains of investigation: understanding the nature and
      distribution of habitable environments in the universe, exploring for habitable
      environments and life in our own solar system, understanding the emergence of
      life, determining how early life on Earth interacted and evolved with its
      changing environment, understanding the evolutionary mechanisms and environmental
      limits of life, determining the principles that will shape life in the future,
      and recognizing signatures of life on other worlds and on early Earth. For each
      of these goals, Science Objectives outline more specific high-priority efforts
      for the next 3-5 years. These 18 objectives are being integrated with NASA
      strategic planning.

PMID- 14577871
TI  - Comment on "Does the rapid appearance of life on Earth suggest that life is
      common in the Universe?".

PMID- 14577873
TI  - To build a pre-RNA.

PMID- 14577876
TI  - Exobiological investigations on Russian spacecrafts.
AB  - To investigate the possibility of prebiotic synthesis of organic molecules in
      open space, conditions involved irradiating nucleosides and inorganic phosphate
      during five Earth-orbiting Russian space missions that included Salut-7 (13- and
      16-month missions), Mir, Bion-11, and Cosmos-2044. Dry films of samples were
      exposed from 2 weeks up to 16 months to the entire set of factors encountered in
      open space during Earth-orbiting missions. After each mission, products
      synthesized during flight and any compounds that remained undegraded were
      analyzed. The analyses demonstrated that increased flight duration led to the
      decay of both synthesized nucleotides and initial nucleosides. Corresponding
      laboratory experiments indicated that infrared radiation caused the greatest
      amount of decay to products of prebiotic reactions. Experiments revealed that 5'
      mononucleotides were the main chemical products of the major derivatives
      synthesized of certain nucleosides. Exposure to ultraviolet (UV) C(145) was more
      effective than UVC(254) in producing a comparatively higher yield of
      mononucleotides, while the energy flux of the latter was one order of magnitude
      less (10(-7) as compared with 10(-6) for UVC(145)). In the course of the
      laboratory simulation experiments the heating of solid samples yielded the
      greatest production amount (6.34% for adenosine derivatives).

PMID- 14577877
TI  - Magnetotactic bacteria on Earth and on Mars.
AB  - Continued interest in the possibility of evidence for life in the ALH84001
      Martian meteorite has focused on the magnetite crystals. This review is
      structured around three related questions: is the magnetite in ALH84001 of
      biological or non-biological origin, or a mixture of both? does magnetite on
      Earth provide insight to the plausibility of biogenic magnetite on Mars? could
      magnetotaxis have developed on Mars? There are credible arguments for both the
      biological and non-biological origin of the magnetite in ALH84001, and we suggest
      that more studies of ALH84001, extensive laboratory simulations of non-biological
      magnetite formation, as well as further studies of magnetotactic bacteria on
      Earth will be required to further address this question. Magnetite grains
      produced by bacteria could provide one of the few inorganic traces of past
      bacterial life on Mars that could be recovered from surface soils and sediments.
      If there was biogenic magnetite on Mars in sufficient abundance to leave fossil
      remains in the volcanic rocks of ALH84001, then it is likely that better
      preserved magnetite will be found in sedimentary deposits on Mars. Deposits in
      ancient lakebeds could contain well-preserved chains of magnetite clearly
      indicating a biogenic origin.

PMID- 14577878
TI  - The catalytic potential of cosmic dust: implications for prebiotic chemistry in
      the solar nebula and other protoplanetary systems.
AB  - The synthesis of important prebiotic molecules is fundamentally reliant on basic
      starting ingredients: water, organic species [e.g., methane (CH(4))], and reduced
      nitrogen compounds [e.g., ammonia (NH(3)), methyl cyanide (CH(3)CN) etc.].
      However, modern studies conclude that the primordial Earth's atmosphere was too
      rich in CO, CO(2), and water to permit efficient synthesis of such reduced
      molecules as envisioned by the classic Miller-Urey experiment. Other proposed
      sources of terrestrial nitrogen reduction, like those within submarine vent
      systems, also seem to be inadequate sources of chemically reduced C-H-O-N
      compounds. Here, we demonstrate that nebular dust analogs have impressive
      catalytic properties for synthesizing prebiotic molecules. Using a catalyst
      analogous to nebular iron silicate condensate, at temperatures ranging from 500K
      to 900K, we catalyzed both the Fischer-Tropsch conversion of CO and H(2) to
      methane and water, and the corresponding Haber-Bosch synthesis of ammonia from
      N(2) and H(2). Remarkably, when CO, N(2), and H(2) were allowed to react
      simultaneously, these syntheses also yielded nitrogen-containing organics such as
      methyl amine (CH(3)NH(2)), acetonitrile (CH(3)CN), and N-methyl methylene imine
      (H(3)CNCH(2)). A fundamental consequence of this work for astrobiology is the
      potential for a natural chemical pathway to produce complex chemical building
      blocks of life throughout our own Solar System and beyond.

PMID- 14577879
TI  - Synchronized SETI-the case for "opposition".
AB  - If the signals being sought in search for extraterrestrial intelligence (SETI)
      programs exist but are brief (for example, they are produced intermittently to
      conserve energy), then it is essential to know when these signals will arrive at
      the Earth. Different types of transmitter/receiver synchronization schemes are
      possible, which vary in the relative amount of effort required by the transmitter
      and the receiver. The case is made for a scheme that is extremely simple for the
      receiver: Make observations of a target when it is at maximum angular distance
      from the Sun (i.e., "opposition"). This strategy requires that the transmitter
      has accurate knowledge of the distance and proper motion of the Sun and the orbit
      of the Earth. It is anticipated that within the next 10-20 years it will be
      possible to detect directly nearby extrasolar planets of approximately
      terrestrial mass. Since extraterrestrial transmitters are expected to have
      significantly more advanced technology, it is not unreasonable to expect that
      they would be able to detect the presence of the Earth and measure its orbit at
      even greater distances. This strategy is simple to implement, and opposition is
      also typically the time when observations are easiest to make. Limited opposition
      surveys contained in a number of all-sky surveys have already been performed.
      However, full-sky opposition surveys are best suited to detectors with very large
      fields of view.

PMID- 14577880
TI  - Delayed gratification habitable zones: when deep outer solar system regions
      become balmy during post-main sequence stellar evolution.
AB  - Like all low- and moderate-mass stars, the Sun will burn as a red giant during
      its later evolution, generating of solar luminosities for some tens of millions
      of years. During this post-main sequence phase, the habitable (i.e., liquid
      water) thermal zone of our Solar System will lie in the region where Triton,
      Pluto-Charon, and Kuiper Belt objects orbit. Compared with the 1 AU habitable
      zone where Earth resides, this "delayed gratification habitable zone" (DGHZ) will
      enjoy a far less biologically hazardous environment - with lower harmful
      radiation levels from the Sun, and a far less destructive collisional
      environment. Objects like Triton, Pluto-Charon, and Kuiper Belt objects, which
      are known to be rich in both water and organics, will then become possible sites
      for biochemical and perhaps even biological evolution. The Kuiper Belt, with
      >10(5) objects > or =50 km in radius and more than three times the combined
      surface area of the four terrestrial planets, provides numerous sites for
      possible evolution once the Sun's DGHZ reaches it. The Sun's DGHZ might be
      thought to only be of academic interest owing to its great separation from us in
      time. However, approximately 10(9) Milky Way stars burn as luminous red giants
      today. Thus, if icy-organic objects are common in the 20-50 AU zones of these
      stars, as they are in our Solar System (and as inferred in numerous main sequence
      stellar disk systems), then DGHZs may form a niche type of habitable zone that is
      likely to be numerically common in the Galaxy.

PMID- 14577881
TI  - Multifrequency electron spin resonance detection of solid-state organic free
      radicals in HCN polymer and a Titan tholin.
AB  - Macromolecules derived from hydrogen cyanide (HCN) may be major components of the
      dark matter observed in bodies in the outer Solar System, which include comets
      and asteroids. HCN oligomers and polymers are readily formed at room temperature
      and react with water to produce polypeptides and alpha-amino acids or undergo
      pyrolysis to produce nitrogen heterocycles. Electron spin resonance (ESR)
      spectroscopy shows that HCN polymer mixtures contain a significant amount of long
      lived organic free radicals that are primarily carbon-based. For comparison, we
      have also examined samples of tholins produced from experimental analogs of Titan
      aerosols, which has been shown by trace organic analysis to consist partly of HCN
      polymer. The "Titan tholin" exhibits at least two ESR signals that can be
      assigned to nitrogen- and carbon-centered radicals, although heating the sample
      eliminates the nitrogen centers and increases the signal from the carbon centers.
      This result suggests that the nitrogen-centered radicals may be thermodynamically
      less stable, but are kinetically trapped during the spark-discharge reactions
      that produce tholins from mixtures of gases such as methane and nitrogen. The
      results strongly support previous proposals of free radical mechanisms for HCN
      polymerization.

PMID- 14577882
TI  - Supercooled water brines within permafrost-an unknown ecological niche for
      microorganisms: a model for astrobiology.
AB  - This study describes brine lenses (cryopegs) found in Siberian permafrost derived
      from ancient marine sediment layers of the Arctic Ocean. The cryopegs were formed
      and isolated from sediment ~100,000-120,000 years ago. They remain liquid at the
      in situ temperature of -10 degrees C as a result of their high salt content (170
      300 g/L). [(14)C] Glucose is taken up by the cryopeg biomass at -15 degrees C,
      indicating microbial metabolism at low temperatures in this habitat. Furthermore,
      aerobic, anaerobic heterotrophs, sulfate reducers, acetogens, and methanogens
      were detected by most probable number analysis. Two psychrophilic microbes were
      isolated from the cryopegs, a Clostridium and a Psychrobacter. The closest
      relatives of each were previously isolated from Antarctica. The cryopeg econiche
      might serve as a model for extraterrestrial life, and hence is of particular
      interest to astrobiology.

PMID- 14577883
TI  - Subfreezing activity of microorganisms and the potential habitability of Mars'
      polar regions.
AB  - The availability of water-ice at the surface in the Mars polar cap and within the
      top meter of the high-latitude regolith raises the question of whether liquid
      water can exist there under some circumstances and possibly support the existence
      of biota. We examine the minimum temperatures at which liquid water can exist at
      ice grain-dust grain and ice grain-ice grain contacts, the minimum subfreezing
      temperatures at which terrestrial organisms can grow or multiply, and the maximum
      temperatures that can occur in martian high-latitude and polar regions, to see if
      there is overlap. Liquid water can exist at grain contacts above about -20
      degrees C. Measurements of growth in organisms isolated from Siberian permafrost
      indicate growth at -10 degrees C and metabolism at -20 degrees C. Mars polar and
      high-latitude temperatures rise above -20 degrees C at obliquities greater than
      ~40 degrees, and under some conditions rise above 0 degrees C. Thus, the
      environment in the Mars polar regions has overlapped habitable conditions within
      relatively recent epochs, and Mars appears to be on the edge of being habitable
      at present. The easy accessibility of the polar surface layer relative to the
      deep subsurface make these viable locations to search for evidence of life.

PMID- 14577884
TI  - Morphological biosignatures and the search for life on Mars.
AB  - This report provides a rationale for the advances in instrumentation and
      understanding needed to assess claims of ancient and extraterrestrial life made
      on the basis of morphological biosignatures. Morphological biosignatures consist
      of bona fide microbial fossils as well as microbially influenced sedimentary
      structures. To be recognized as evidence of life, microbial fossils must contain
      chemical and structural attributes uniquely indicative of microbial cells or
      cellular or extracellular processes. When combined with various research
      strategies, high-resolution instruments can reveal such attributes and elucidate
      how morphological fossils form and become altered, thereby improving the ability
      to recognize them in the geological record on Earth or other planets. Also,
      before fossilized microbially influenced sedimentary structures can provide
      evidence of life, criteria to distinguish their biogenic from non-biogenic
      attributes must be established. This topic can be advanced by developing process
      based models. A database of images and spectroscopic data that distinguish the
      suite of bona fide morphological biosignatures from their abiotic mimics will
      avoid detection of false-positives for life. The use of high-resolution imaging
      and spectroscopic instruments, in conjunction with an improved knowledge base of
      the attributes that demonstrate life, will maximize our ability to recognize and
      assess the biogenicity of extraterrestrial and ancient terrestrial life.

PMID- 14577885
TI  - Submicron magnetite grains and carbon compounds in Martian meteorite ALH84001:
      inorganic, abiotic formation by shock and thermal metamorphism.
AB  - Purported biogenic features of the ALH84001 Martian meteorite (the carbonate
      globules, their submicron magnetite grains, and organic matter) have reasonable
      inorganic origins, and a comprehensive hypothesis is offered here. The carbonate
      globules were deposited from hydrothermal water, without biological mediation.
      Thereafter, ALH84001 was affected by an impact shock event, which raised its
      temperature nearly instantaneously to 500-700K, and induced iron-rich carbonate
      in the globules to decompose to magnetite and other minerals. The rapidity of the
      temperature increase caused magnetite grains to nucleate in abundance; hence
      individual crystals were very small. Nucleation and growth of magnetite crystals
      were fastest along edges and faces of the precursor carbonate grains, forcing the
      magnetite grains to be platy or elongated, including the "truncated hexa
      octahedra" shape. ALH84001 had formed at some depth within Mars where the
      lithostatic pressure was significantly above that of Mars' surface. Also, because
      the rock was at depth, the impact heat dissipated slowly. During this interval,
      magnetite crystals approached chemical equilibria with surrounding minerals and
      gas. Their composition, nearly pure Fe(3)O(4), reflects those of equilibria;
      elements that substitute into magnetite are either absent from iron-rich
      carbonate (e.g., Ti, Al, Cr), or partitioned into other minerals during magnetite
      formation (Mg, Mn). Many microstructural imperfections in the magnetite grains
      would have annealed out as the rock cooled. In this post-shock thermal regime,
      carbon-bearing gas from the decomposition of iron carbonates reacted with water
      in the rock (or from its surroundings) to produce organic matter via Fischer
      Tropschlike reactions. Formation of such organic compounds like polycyclic
      aromatic hydrocarbons would have been catalyzed by the magnetite (formation of
      graphite, the thermochemically stable phase, would be kinetically hindered).

PMID- 14577886
TI  - Temperature and moisture conditions for life in the extreme arid region of the
      Atacama desert: four years of observations including the El Nino of 1997-1998.
AB  - The Atacama along the Pacific Coast of Chile and Peru is one of the driest and
      possibly oldest deserts in the world. It represents an extreme habitat for life
      on Earth and is an analog for life in dry conditions on Mars. We report on four
      years (September 1994-October 1998) of climate and moisture data from the extreme
      arid region of the Atacama. Our data are focused on understanding moisture
      sources and their role in creating suitable environments for photosynthetic
      microorganisms in the desert surface. The average air temperature was 16.5
      degrees C and 16.6 degrees C in 1995 and 1996, respectively. The maximum air
      temperature recorded was 37.9 degrees C, and the minimum was -5.7 degrees C.
      Annual average sunlight was 336 and 335 W m(-2) in 1995 and 1996, respectively.
      Winds averaged a few meters per second, with strong fohn winds coming from the
      west exceeding 12 m s(-1). During our 4 years of observation there was only one
      significant rain event of 2.3 mm, which occurred near midnight local time. We
      suggest that this event was a rainout of a heavy fog. It is of interest that the
      strong El Nino of 1997-1998 brought heavy rainfall to the deserts of Peru, but
      did not bring significant rain to the central Atacama in Chile. Dew occurred at
      our station frequently following high nighttime relative humidity, but is not a
      significant source of moisture in the soil or under stones. Groundwater also does
      not contribute to surface moisture. Only the one rain event of 2.3 mm resulted in
      liquid water in the soil and beneath stones for a total of only 65-85 h over 4
      years. The paucity of liquid water under stones is consistent with the apparent
      absence of hypolithic (under-stone) cyanobacteria, the only known primary
      producers in such extreme deserts.

PMID- 14577887
TI  - Biological potential of Martian hydrothermal systems.
AB  - A source of energy to power metabolism may be a limiting factor in the abundance
      and spatial distribution of past or extant life on Mars. Although a global
      average of chemical energy available for microbial metabolism and biomass
      production on Mars has been estimated previously, issues of how the energy is
      distributed and which particular environments have the greatest potential to
      support life remain unresolved. We address these issues using geochemical models
      to evaluate the amounts of chemical energy available in one potential biological
      environment, Martian hydrothermal systems. In these models, host rock
      compositions are based upon the compositions of Martian meteorites, which are
      reacted at high temperature with one of three groundwater compositions. For each
      model, the values for Gibbs energy of reactions that are important for
      terrestrial chemosynthetic organisms and likely representative for putative
      Martian microbes are calculated. Our results indicate that substantial amounts of
      chemical energy may be available in these systems, depending most sensitively
      upon the composition of the host rock. From the standpoint of sources of
      metabolic energy, it is likely that suitable environments exist to support
      Martian life.

PMID- 14577888
TI  - Climate model studies of synchronously rotating planets.
AB  - M stars constitute 75% of main sequence stars though, until recently, their star
      systems have not been considered suitable places for habitable planets to exist.
      In this study the climate of a synchronously rotating planet around an M dwarf
      star is evaluated using a three-dimensional global atmospheric circulation model.
      The presence of clouds and evaporative cooling at the surface of the planet
      result in a cooler surface temperature at the subsolar point. Water ice forms at
      the polar regions and on the dark side, where the minimum temperature lies
      between -30 degrees C and 0 degrees C. As expected, rainfall is extremely high on
      the starlit side and extremely low on the dark side. The presence of a dry
      continent causes higher temperatures on the dayside, and allows accumulation of
      snow on the nightside. The absence of any oceans leads to higher day-night
      temperature differences, consistent with previous work. The present study
      reinforces recent conclusions that synchronously rotating planets within the
      circumstellar habitable zones of M dwarf stars should be habitable, and therefore
      M dwarf systems should not be excluded in future searches for exoplanets.

PMID- 14577890
TI  - Time is of the essence: A selective review of the fall and rise of brief therapy
      research.
AB  - For compelling reasons of equity and the advance of public health, brief
      psychotherapy has become the dominant format in both practice and research. One
      consequence of this is the apparent decline of a distinct stream of brief therapy
      research. However, much of the agenda formerly identified with that research
      stream is of increasing importance to the field. Time is indeed of the essence in
      current psychotherapy research. For example, factors conducive to the time
      efficiency of brief psychodynamic therapy have been described recently. The
      important question 'How much therapy is enough?' has been addressed by studies
      inspired by the dose-response analysis of Howard and colleagues. The value of
      ultra-brief interventions has been examined. These issues are considered in a
      selective review, drawing in particular on the work of the Sheffield/Leeds
      psychotherapy of depression research group. This research treats the number of
      treatment sessions as an independent variable, thereby providing a causal
      analysis of the dose-response relationship over a range from two to 16 sessions,
      illuminated by a comparative analysis of change processes in treatments of
      different durations. Its results enable some specification of the extent and
      nature of incremental benefit derived from additional sessions in the
      psychotherapy of depression.

PMID- 14577891
TI  - Social comparison and submissive behaviour in eating disorder patients.
AB  - Animal analogues of anorexia nervosa suggest that submissive behaviour and social
      defeat may be implicated in the onset of wasting diseases. Data from human
      sufferers of anorexia nervosa and bulimia nervosa are also consistent with the
      presence of submissive behaviours and perceived low social rank (e.g. low self
      esteem, helplessness, and feelings of shame). A total of 101 patients with eating
      disorders completed the Submissive Behaviour Scale and the Social Comparison
      Rating Scale, and their responses were compared with 101 age- and sex-matched
      student controls. Patients with eating disorders reported significantly higher
      levels of submissive behaviour and a more unfavourable social comparison than did
      student controls. Furthermore, levels of submissive behaviour and unfavourable
      social comparison were significantly related to severity of eating disorder
      symptoms, even after taking account of depressive symptoms and other
      psychopathology. These preliminary results suggest that ranking theory may have
      some application to eating disorders. Further research is required to determine
      whether rank plays a specific role in eating disorders (beyond the increased
      rates of depression which also occur in eating disorders) and, if so, what is its
      precise role.

PMID- 14577892
TI  - Verbal and non-verbal disclosure of recalled negative experiences: relation to
      well-being.
AB  - This study investigated the relationship between methods of disclosure of
      recalled negative experience and well-being. Six first-year undergraduate class
      groups (N = 100) at an Australian university completed pre- and post-intervention
      measures of psychological and psychophysical well-being. For the disclosure
      intervention, three groups wrote, drew, or drew-and-wrote about a recalled
      negative experience (RNE groups); the three non-disclosure groups wrote, drew, or
      drew-and-wrote on neutral topics (NT groups). The expectation that disclosure of
      negative experiences would enhance well-being was partly supported, with writing
      and drawing-and-writing disclosure groups reporting increased psychological, but
      not psychophysical, well-being. As predicted, verbal disclosure methods were more
      effective than non-verbal methods, with the draw-and-write group showing the
      greatest improvement. Unexpectedly, disclosure via drawing alone was associated
      with decreased psychological well-being. Against predictions, changes were found
      in two NT groups: The draw-and-write group reported improved psychological, and
      the draw group improved psychophysical well-being. It was concluded that verbal
      disclosure, especially when combined with the non-verbal method of drawing, may
      enhance psychological well-being, but that drawing, without accompanying
      verbalization, may decrease psychological well-being. It is suggested that future
      studies address variables such as level of disclosure, content and time of the
      negative experience, with time taken to manifest changes in well-being, using
      both subjective and objective indicators.

PMID- 14577893
TI  - Positive change processes and post-traumatic growth in people who have
      experienced childhood abuse: understanding vehicles of change.
AB  - Post-traumatic growth is an emerging area of research concerned with the positive
      psychological changes that can follow the experience of traumatic events. The aim
      of this study is to explore themes of post-traumatic growth within personal
      experience narratives of individuals who have experienced some form of early
      emotional, physical, or sexual abuse. Using thematic analysis, we identified
      three domains of themes related to positive change processes: inner drive toward
      growth, vehicles of change, and psychological changes. Understanding the
      different vehicles of change has implications for facilitating post-traumatic
      growth in clients who have experienced traumatic events.

PMID- 14577894
TI  - Narrative transformation as an outcome in the psychotherapy of schizophrenia.
AB  - Assertions that changes or transformations in narratives contribute significantly
      to recovery from schizophrenia persist as a cornerstone of some psychotherapies.
      Yet when narrative transformation occurs in schizophrenia, what is there about
      the client's story that tangibly changes, and how might that be measured? To
      address this issue, we review literature on the importance of narrative
      transformation and identify narrative qualities that might theoretically change.
      We then report content and thematic analyses of the qualities of narratives that
      might potentially change over 14 months of psychotherapy. These analyses suggest
      that narratives in schizophrenia may gain complexity and dynamism, but the
      changes do not entail the creation of a new story or the 'awakening' of an 'old'
      self. From these analyses, the hypothesis that narrative transformation may occur
      in terms of growth in the richness of the internal dialogue that produces
      narrative is posed for future research.

PMID- 14577895
TI  - The Greek version of the Revised Person's Relating to Others Questionnaire (PROQ2
      GR): psychometric properties and factor structure.
AB  - The Revised Person's Relating to Others Questionnaire (PROQ2) is a self
      administered questionnaire of 96 items for measuring a person's negative
      relating. Its eight scales correspond to the eight octants of the theoretical
      structure called the interpersonal octagon, which is based upon the assumption
      that relating occurs along a horizontal, close-distant axis and a vertical, upper
      lower axis. The present study concerns the Greek translation of the questionnaire
      called the PROQ2-GR. The psychometric properties and the factor structure of the
      PROQ2-GR were studied in a Greek population sample of 457. The findings were
      compared with those of an English population sample of 276. All scales showed
      good internal reliability. Four factors were extracted, representing the four
      main poles of the interpersonal octagon, with good psychometric properties. The
      positive correlations between all adjacent scales and the negative correlations
      between certain pairs of opposite scales are as would be expected in a model of
      circular ordering. The PROQ2-GR showed a greater degree of bipolarity than the
      PROQ2. Women were significantly more upper close and neutral close than men. The
      Greeks had a higher total mean score than the English and had higher mean scores
      on five out of the eight scales.

PMID- 14577896
TI  - Anomalous experiences and the contents of persecutory delusions during acute
      psychotic episodes.
AB  - Criteria for judging the presence of persecutory delusions, and theoretical
      distinctions between different kinds of persecutory delusions, depend on the
      identification of the contents of such delusions. The first aim of this study was
      to assess whether contents can be assessed reliably. It has been suggested that
      anomalous experiences are involved in the formation and maintenance of delusions.
      The second aim of this study was to assess whether independent judges could agree
      when persecutory delusions depend on such experiences. Twenty-two inpatients
      suffering from acute psychotic episodes were recruited. Two independent raters
      categorized the contents of their delusions in terms of the timing, agent,
      intention, motivation, type, and severity of harm using information from a
      variety of sources. Agreement between the raters was adequate for all content
      areas and for judgments of associations with anomalous experiences. Using ideas
      of reference as evidence for the persecution was associated with believing that
      the harm is already very severe, that multiple types of harm are occurring, and
      that worse persecution is imminent. Theoretical explanations need to be
      elaborated to account for the variety of contents that can be identified
      reliably. Associations with anomalous experiences might guide such elaborations.

PMID- 14577897
TI  - Family representations in relationship episodes of patients with a diagnosis of
      bulimia nervosa.
AB  - The influence of the family on the development and the maintenance of bulimia
      nervosa can be seen both biologically and psychosocially. Genetic influences are
      discussed, but their effects do not explain the aetiology exclusively. Clinical
      observations and research findings support the role of family dynamics, family
      environment, and family functioning. In particular, a low level of cohesion, a
      lower degree of expressiveness, and more conflicts seem to characterize the
      family of patients with a diagnosis of bulimia nervosa. The present study
      addresses the question of how patients suffering from bulimia differ from other
      patients in psychotherapy and from non-clinical control subjects in the way they
      perceive their ongoing and their past family relationships. The Core Conflictual
      Relationship Theme method is applied to narrative material from patients
      belonging to these three groups. Results show expected differences between
      patients and normal control subjects and virtually no differences between the
      group of patients with a diagnosis of bulimia nervosa and the group of patients
      with diagnoses different from bulimia.

PMID- 14577898
TI  - Disease management accreditation: quality improvement in a new health care
      environment.

PMID- 14577899
TI  - Disease management can truly add value for providers.

PMID- 14577900
TI  - Interventions to improve chronic illness care: evaluating their effectiveness.
AB  - Three overlapping initiatives can be found in the effort to improve the
      management of chronic illness: the report card initiative, the disease management
      industry, and "Improving Chronic Illness Care." The third of these initiatives
      proposes the Chronic Care Model to assist provider organizations in chronic care
      improvement. The Chronic Care Model is made up of six major elements: community
      resources, the health care system surrounding the provider organization, patient
      self-management, decision support, delivery system redesign, and clinical
      information systems. Within these elements are a number of components, for
      example, clinical practice guidelines, reminder prompts, disease registries,
      provider feedback systems, primary care teams, planned chronic care visits, and
      case management. A literature review is provided to summarize the effectiveness
      of these Chronic Care Model components.

PMID- 14577901
TI  - Cultivating a disease management partnership: a value-chain model.
AB  - Disease management (DM) is one of the health care industry's more innovative
      value-chain models, whereby multiple relationships are created to bring complex
      and time-sensitive services to market. The very nature of comprehensive, seamless
      DM provided through an outsourced arrangement necessitates a level of
      cooperation, trust, and synergy that may be lacking from more traditional vendor
      customer relationships. This discussion highlights the experience of one health
      plan and its vendor partner and their approach to the development and delivery of
      an outsourced heart failure (HF) DM program. The program design and rollout are
      discussed within principles adapted from the theoretical framework of a value
      chain model. Within the value-chain model, added value is created by the
      convergence and synergistic integration of the partners' discrete strengths.
      Although each partner brings unique attributes to the relationship, those
      attributes are significantly enhanced by the value-chain model, thus allowing
      each party to bring the added value of the relationship to their respective
      customers. This partnership increases innovation, leverages critical
      capabilities, and improves market responsiveness. Implementing a comprehensive,
      outsourced DM program is no small task. DM programs incorporate a broad array of
      services affecting nearly every department in a health plan's organization. When
      true seamless integration between multiple organizations with multiple
      stakeholders is the objective, implementation and ongoing operations can become
      even more complex. To effectively address the complexities presented by an HF DM
      program, the parties in this case moved beyond a typical purchaser-vendor
      relationship to one that is more closely akin to a strategic partnership. This
      discussion highlights the development of this partnership from the perspective of
      both organizations, as revealed through contracting and implementation
      activities. It is intended to provide insight into the program development and
      rollout processes that one health plan and its partner have adopted to advance a
      DM model that integrates appropriately within the local environment. This
      discussion also highlights how an organizational culture can shift from an
      emphasis on cost, growth, and control to an emphasis on quality, innovation, and
      service within a value-chain model.

PMID- 14577902
TI  - Management of osteoporosis in women aged 50 and older with osteoporosis-related
      fractures in a managed care population.
AB  - This study describes the pattern of evaluation and management of osteoporosis in
      women aged 50 and older following an osteoporosis-related fracture, conducted as
      a retrospective cohort study using the administrative claims database of a
      managed care organization. Subjects were women, aged 50 years and older, with at
      least one osteoporosis-related fracture in the years 1996-1998 who were
      continuously enrolled in the system's health plan for at least 6 months prior to
      and post-fracture. Bone mineral density (BMD) testing, diagnosis of osteoporosis,
      and treatment with any Food and Drug Administration-approved medication for
      osteoporosis were identified using CPT, ICD-9, and National Drug Codes for the 6
      month post-fracture period. There were 658 women with an osteoporosis-related
      fracture: 189 (29%) hip fractures, 226 (34%) wrist fractures, 127 (19%) vertebral
      fractures, and 116 (18%) rib fractures. In the post-fracture period, 46 (7%)
      underwent BMD testing, 153 (23%) had a diagnosis of osteoporosis, and 220 (31%)
      were treated with a medication approved for the prevention or treatment of
      osteoporosis. Of the 220 women with medication claims, 124 (56%) were for
      estrogen, and 96 (44%) were for other antiresorptive agents. Of the 507 women who
      did not have medication claims during the 6 months prior to the fracture, only
      17% had new fills after the fracture. Management of osteoporosis in women aged 50
      and older with fractures was inadequate, despite the high risk of subsequent
      fractures and recommendations that osteoporosis be the presumptive diagnosis.
      Significant opportunity exists for improvement in assuring post-fracture followup
      care.

PMID- 14577903
TI  - An assessment of the total population approach for evaluating disease management
      program effectiveness.
AB  - A key challenge currently facing the disease management industry is accurately
      demonstrating program effectiveness at controlling utilization of services and
      medical costs of populations with chronic disease. The most common method used in
      the disease management industry to date for determining financial outcomes is
      referred to as the "total population approach." This model is a pretest-posttest
      design, which is a relatively weak research and evaluation technique. This paper
      describes the "total population approach," details many of the biases and
      confounding factors that may influence outcomes using this method, and
      illustrates the potential consequences of these factors.

PMID- 14577904
TI  - Care management for persistent pain: an introduction.
AB  - Persistent pain is a frequently occurring condition with significant economic,
      clinical, and humanistic implications, for both individuals and society. Current
      literature, however, points to unresolved issues with regard to its
      identification, assessment, diagnosis, and treatment, and a number of suggestions
      have been made for improving the quality of care for pain sufferers. Because
      persistent pain shares many of the salient features of other chronic conditions
      such as diabetes and congestive heart failure, it is reasonable to believe that
      the adoption of a coordinated approach to care management could substantially
      improve the quality of care. Several strategies--including identification,
      appropriate referral, education, and planning--can and should be implemented to
      offer comprehensive, individualized treatment alternatives that are not currently
      available and that improve patient outcomes, including quality of life.

PMID- 14577905
TI  - Use of the short form 36 in a primary care based disease management program for
      patients with congestive heart failure.
AB  - While disease management has been described as an important strategy for the care
      of patients with congestive heart failure (CHF) in the managed care setting,
      little is known about the impact of this approach on overall health-related
      quality of life. In this study the Short Form 36 (SF-36) was administered to all
      patients entering CHF disease management at the time of program entry and at 1
      year following entry. Scores on the eight subscales and the two composite scales
      were calculated and compared before and after. Patients were enrolled from a
      mixed-model health maintenance organization (HMO) with 34,740 Medicare + Choice
      enrollees residing in 38 counties in central and northeastern Pennsylvania. Two
      hundred sixty-eight continuously enrolled patients in an HMO-sponsored CHF
      disease state management program with completed baseline and follow-up SF-36
      surveys were sampled. All patients entered into disease management received
      primary care based, nurse-directed education about CHF self-management including
      instruction on etiology of CHF, the importance of medication compliance, home
      care services if indicated, monitoring weight gain, increased understanding of
      the warning signs of worsening CHF, and coaching on strategies to contact a
      physician in a timely manner when CHF worsens. Nurses also facilitated for CHF
      guidelines among primary care physicians, including the need to obtain a baseline
      assessment of cardiac function, prescribe angiotensin I-converting enzyme (ACE)
      inhibitors and beta blockers when appropriate, and initiated appropriate
      specialist referral. Compared with enrollees who did not complete a pair of SF-36
      surveys, the 268 respondents were younger and had a significantly higher rate of
      cardiac imaging as well as use of ACE inhibitors and beta blocker medications.
      Analysis of the SF-36 data revealed that three of the eight (Role Physical,
      General Health Perceptions, and Role Emotional) subscales increased in a
      statistically significant manner, as did the Mental Health Composite Score. No
      statistically significant declines in SF-36 scores were observed. Despite
      limitations to our study, we found disease management for patients with CHF can
      be associated with significant improvements in quality of life as measured by the
      SF-36. Compared with nonrespondents, respondents had a higher prevalence of
      cardiac imaging, ACE inhibitor use, and beta blocker medication use. Our findings
      are also limited by a lack of a control group with the possibility that the
      improvements we observed were unrelated to the disease management intervention.
      However, our findings and success with the use of this tool indicate the SF-36
      can be an important part of the ongoing assessment of patients in a disease
      management program for CHF.

PMID- 14577906
TI  - Administration of parathyroid hormone, prostaglandin E2, or 1-alpha,25
      dihydroxyvitamin D3 restores the bone inductive activity of rhBMP-2 in aged rats.
AB  - Bone morphogenetic protein (BMP) induces bone formation in young rodents, but
      aging causes a reduction in the bone-forming ability of BMP. Most patients who
      require bone reconstruction are relatively old. Accordingly, we examined whether
      anabolic hormones could restore the bone inductive activity of rhBMP-2 in aged
      rats. rhBMP-2 in a carrier pellet was implanted subcutaneously in both 4- and 50
      week-old female Wistar rats. PTH, PGE2, or 1,25(OH)2D3 was injected every day
      during the period of BMP implantation. The pellets were harvested, and were
      examined both histologically and biochemically 2 weeks after implantation. Bone
      forming ability was measured by alkaline phosphatase (ALP) activity and calcium
      (Ca) content. Pellets in 50-week-old rats showed a significant reduction in bone
      formation compared to pellets in 4-week-old rats. However, daily injections of
      PTH into 50-week-old rats restored both ALP activity (103 +/- 4.6%) and Ca
      content (105 +/- 2.6%). 1,25(OH)2D3 and PGE2 also restored Ca content (103 +/-
      4.5% and 98 +/- 3.8%, respectively) and stimulated ALP activity (142 +/- 2.3% and
      133 +/- 3.6%). These results show that the administration of these hormones
      restores bone-forming ability in aged rats. A combination treatment of these
      hormones with rhBMP-2 might be applicable to the reconstruction of bone defects
      in elderly patients.

PMID- 14577907
TI  - Regenerative medicine/cellular engineering for diseases of the head and neck.

PMID- 14577908
TI  - Tissue engineering in otorhinolaryngology.
AB  - Tissue engineering is a field of research with interdisciplinary cooperation
      between clinicians, cell biologists, and materials research scientists. Many
      medical specialties apply tissue engineering techniques for the development of
      artificial replacement tissue. Stages of development extend from basic research
      and preclinical studies to clinical application. Despite numerous established
      tissue replacement methods in otorhinolaryngology, head and neck surgery, tissue
      engineering techniques opens up new ways for cell and tissue repair in this
      medical field. Autologous cartilage still remains the gold standard in plastic
      reconstructive surgery of the nose and external ear. The limited amount of
      patient cartilage obtainable for reconstructive head and neck surgery have
      rendered cartilage one of the most important targets for tissue engineering in
      head and neck surgery. Although successful in vitro generation of bioartificial
      cartilage is possible today, these transplants are affected by resorption after
      implantation into the patient. Replacement of bone in the facial or cranial
      region may be necessary after tumor resections, traumas, inflammations or in
      cases of malformations. Tissue engineering of bone could combine the advantages
      of autologous bone grafts with a minimal requirement for second interventions.
      Three different approaches are currently available for treating bone defects with
      the aid of tissue engineering: (1) matrix-based therapy, (2) factor-based
      therapy, and (3) cell-based therapy. All three treatment strategies can be used
      either alone or in combination for reconstruction or regeneration of bone. The
      use of respiratory epithelium generated in vitro is mainly indicated in
      reconstructive surgery of the trachea and larynx. Bioartificial respiratory
      epithelium could be used for functionalizing tracheal prostheses as well as
      direct epithelial coverage for scar prophylaxis after laser surgery of shorter
      stenoses. Before clinical application animal experiments have to prove
      feasability and safety of the different experimental protocols. All diseases
      accompanied by permanently reduced salivation are possible treatment targets for
      tissue engineering. Radiogenic xerostomia after radiotherapy of malignant head
      and neck tumors is of particular importance here due to the high number of
      affected patients. The number of new diseases is estimated to be over 500,000
      cases worldwide. Causal treatment options for radiation-induced salivary gland
      damage are not yet available; thus, various study groups are currently
      investigating whether cell therapy concepts can be developed with tissue
      engineering methods. Tissue engineering opens up new ways to generate vital and
      functional transplants. Various basic problems have still to be solved before
      clinically applying in vitro fabricated tissue. Only a fraction of all somatic
      organ-specific cell types can be grown in sufficient amounts in vitro. The
      inadequate in vitro oxygen and nutrition supply is another limiting factor for
      the fabrication of complex tissues or organ systems. Tissue survival is doubtful
      after implantation, if its supply is not ensured by a capillary network.

PMID- 14577909
TI  - Regeneration of inner ear cells from stem cell precursors--a future concept of
      hearing rehabilitation?
AB  - The use of stem cells offers new and powerful strategies for future tissue
      development and engineering. Common features of stem cells are both their
      capacity for self-renewal and the ability to differentiate into mature effector
      cells. Since the establishment of embryonic stem cells from early human embryos,
      research on and clinical application of human ES cells belong to the most
      controversial topics in our society. Great hopes are based upon the remarkable
      observation that human ES cells can be greatly expanded in vitro, and that they
      can differentiate into various clinically important cell types. Recent advances
      in the cloning of mammals by nuclear transplantation provide new concepts for
      autologous replacement of damaged and degenerated tissues. In contrast, somatic
      stem cells of the adult organism were considered to be more restricted in their
      developmental potential. However, recent investigations suggest that somatic stem
      cells may have a wider differentiation potential than previously thought. In
      otology, initial experiments have revealed neural stem cell survival in cochlear
      cell cultures and under neurotrophin influence, neural stem cells seemed to
      develop into a neuronal phenotype. Further studies have to be carried out to
      investigate the full potential of stem cells as well as the molecular mechanisms
      that are involved in regulating cellular identity and plasticity. Clinically,
      advances in stem cell biology may provide a permanent source of replacement cells
      for treating human diseases and could open the development of new concepts for
      cell and tissue regeneration for a causal treatment of chronic degenerative
      diseases.

PMID- 14577910
TI  - Regenerative medicine for diseases of the head and neck: principles of in vivo
      regeneration.
AB  - The application of endogenous regeneration in regenerative medicine is based on
      the concept of inducing regeneration of damaged or lost tissues from residual
      tissues in situ. Therefore, endogenous regeneration is also termed in vivo
      regeneration as opposed to mechanisms of ex vivo regeneration which are applied,
      for example, in the field of tissue engineering. The basic science foundation for
      mechanisms of endogenous regeneration is provided by the field of regenerative
      biology. The ambitious vision for the application of endogenous regeneration in
      regenerative medicine is stimulated by investigations in the model organisms of
      regenerative biology, most notably hydra, planarians and urodeles. These model
      organisms demonstrate remarkable regenerative capabilities, which appear to be
      conserved over large phylogenetical stretches with convincing evidence for a
      homologue origin of an endogenous regenerative capability. Although the
      elucidation of the molecular and cellular mechanisms of these endogenous
      regenerative phenomena is still in its beginning, there are indications that
      these processes have potential to become useful for human benefit. Such
      indications also exist for particular applications in diseases of the head and
      neck region. As such epimorphic regeneration without blastema formation may be
      relevant to regeneration of sensorineural epithelia of the inner ear or the
      olphactory epithelium. Complex tissue lesions of the head and neck as they occur
      after trauma or tumor resections may be approached on the basis of relevant
      mechanisms in epimorphic regeneration with blastema formation.

PMID- 14577911
TI  - The role of growth factors for disease and therapy in diseases of the head and
      neck.
AB  - Growth factors are a large family of polypeptide molecules that regulate cell
      division in many tissues by autocrine or paracrine mechanisms. Depending on what
      receptors are activated, growth factors can initiate mitogenic,
      antiproliferative, or trophic effects, that is, growth factors act as positive or
      negative modulators of cell proliferation. Therefore, growth factors do not only
      play an important role in embryonic development and adult tissue homeostasis, but
      also in pathological situations like infection, wound healing, and tumorigenesis.
      Consequently, the application of growth factors, or vice versa the application of
      substances which are directed against growth factors like antigrowth factor
      antibodies, may have therapeutic applications. This review provides a brief
      account of what we know regarding growth factors in otorhinolaryngology,
      particularly in the field of otology, wound healing, oncology, peripheral nerve
      regeneration, and rhinology.

PMID- 14577912
TI  - Phase I/II clinical trial of a nonreplicative vaccinia virus expressing multiple
      HLA-A0201-restricted tumor-associated epitopes and costimulatory molecules in
      metastatic melanoma patients.
AB  - We performed a phase I/II clinical trial in metastatic melanoma patients with an
      ultraviolet (UV)-inactivated nonreplicating recombinant vaccinia virus enabling
      the expression, from a single construct, of endoplasmic reticulum-targeted HLA
      A0201-restricted Melan-A/MART-1(27-35), gp100(280-288), and tyrosinase(1-9)
      epitopes, together with CD80 and CD86 costimulatory proteins. Corresponding
      soluble peptides were used to boost responses and granulocyte-macrophage colony
      stimulating factor was used as systemic adjuvant. Safety and immunogenicity, as
      monitored with in vitro-restimulated peripheral blood mononuclear cells by
      cytotoxic T lymphocyte precursor (CTLp) frequency analysis and tetramer staining,
      were specifically addressed. Of 20 patients entering the protocol, 2 had to
      withdraw because of rapidly progressing disease. Immune responses were evaluated
      in 18 patients (stage III, n = 5; stage IV, n = 13) and increases in specific
      CTLp frequencies were observed in 15. In 16 patients responsiveness against all 3
      antigens could be analyzed: 7 (43%), including all stage III cases, showed
      evidence of induction of CTLs specific for the three epitopes, and 2 (12%) and 4
      (25%), respectively, showed reactivity against two or one tumor-associated
      antigen. In three stage IV patients no specific CTL reactivity could be induced.
      Increases in CTLp frequency were detected mostly after viral vaccine injections.
      However, in a majority of patients final CTLp levels were comparable to initial
      levels. Tetramer characterization of Melan-A/MART-1(27-35)-specific CTLs during
      the protocol also suggested preferential expansion after recombinant virus
      administration. Vector-specific humoral responses, frequently undetectable in
      stage IV patients, did not appear to prevent tumor-associated antigen-specific
      CTL induction. Aside from a single occurrence of transient grade 3 leukopenia, no
      major clinical toxicity was reported. Seventeen of 18 patients completed the 3
      month trial (one patient died before the last delayed-type hypersensitivity
      test). Three displayed regression of individual metastases, seven had stable
      disease, and progressive disease was observed in seven patients. This is the
      first report on the administration of a UV-inactivated recombinant vaccinia virus
      coexpressing five transgenes in cancer patients. The results described here, in
      terms of safety and immunogenicity, support the use of this reagent in active
      specific immunotherapy.

PMID- 14577914
TI  - Lentivector-mediated transfer of Bmi-1 and telomerase in muscle satellite cells
      yields a duchenne myoblast cell line with long-term genotypic and phenotypic
      stability.
AB  - Conditionally immortalized human cells are valuable substrates for basic biologic
      studies, as well as for the production of specific proteins and for the creation
      of bioartificial organs. We previously demonstrated that the lentivector-mediated
      transduction of immortalizing genes into human primary cells is an efficient
      method for obtaining such cell lines. Here, we used human muscle satellite cells
      as model targets to examine the impact of the transduced genes on the genotypic
      and phenotypic characteristics of the immortalized cells. The most commonly used
      immortalizing gene, the SV40 large T antigen (T-Ag), was extremely efficient at
      inducing the continuous growth of primary myoblasts, but the resulting cells
      rapidly accumulated major chromosomal aberrations and exhibited profound
      phenotypic changes. In contrast, the constitutive expression of telomerase and
      Bmi-1 in satellite cells from a control individual and from a patient suffering
      from Duchenne's muscular dystrophy yielded cell lines that remained diploid and
      conserved their growth factor dependence for proliferation. However, despite the
      absence of detectable cytogenetic abnormalities, clones derived from satellite
      cells of a control individual exhibited a differentiation block in vitro. In
      contrast, a Duchenne-derived cell line exhibited all the phenotypic
      characteristics of its primary parent, including an ability to differentiate
      fully into myotubes when placed in proper culture conditions. This cell line
      should constitute a useful reagent for a wide range of studies aimed at this
      disease.

PMID- 14577915
TI  - Dystrophin delivery in dystrophin-deficient DMDmdx skeletal muscle by isogenic
      muscle-derived stem cell transplantation.
AB  - Duchenne's muscular dystrophy (DMD) is a lethal muscle disease caused by a lack
      of dystrophin expression at the sarcolemma of muscle fibers. We investigated
      retroviral vector delivery of dystrophin in dystrophin-deficient DMD(mdx)
      (hereafter referred to as mdx) mice via an ex vivo approach using mdx muscle
      derived stem cells (MDSCs). We generated a retrovirus carrying a functional human
      mini-dystrophin (RetroDys3999) and used it to stably transduce mdx MDSCs obtained
      by the preplate technique (MD3999). These MD3999 cells expressed dystrophin and
      continued to express stem cell markers, including CD34 and Sca-1. MD3999 cells
      injected into mdx mouse skeletal muscle were able to deliver dystrophin. Though a
      relatively low number of dystrophin-positive myofibers was generated within the
      gastrocnemius muscle, these fibers persisted for up to 24 weeks postinjection.
      The injection of cells from additional MDSC/Dys3999 clones into mdx skeletal
      muscle resulted in varying numbers of dystrophin-positive myofibers, suggesting a
      differential regenerating capacity among the clones. At 2 and 4 weeks
      postinjection, the infiltration of CD4- and CD8-positive lymphocytes and a
      variety of cytokines was detected within the injected site. These data suggest
      that the transplantation of retrovirally transduced mdx MDSCs can enable
      persistent dystrophin restoration in mdx skeletal muscle; however, the
      differential regenerating capacity observed among the MDSC/Dys3999 clones and the
      postinjection immune response are potential challenges facing this technology.

PMID- 14577913
TI  - Interleukin-7 gene-modified dendritic cells reduce pulmonary tumor burden in
      spontaneous murine bronchoalveolar cell carcinoma.
AB  - The antitumor efficiency of dendritic cells transduced with an adenovirus vector
      expressing interleukin (IL)-7 (DC-AdIL-7) was evaluated in a murine model of
      spontaneous bronchoalveolar cell carcinoma. These transgenic mice (CC-10 TAg),
      expressing the SV40 large T antigen under the Clara cell promoter, develop
      bilateral multifocal pulmonary adenocarcinomas and die at 4 months as a result of
      progressive pulmonary tumor burden. Injection of DC-AdIL-7 in the axillary lymph
      node region (ALNR) weekly for 3 weeks led to a marked reduction in tumor burden
      with extensive lymphocytic infiltration of the tumors and enhanced survival. The
      antitumor responses were accompanied by the enhanced elaboration of interferon
      (IFN)-gamma and IL-12 as well as an increase in the antiangiogenic chemokines,
      IFN-gamma-inducible protein 10 (IP-10/CXCL10) and monokine induced by IFN-gamma
      (MIG/CXCL9). In contrast, production of the immunosuppressive mediators IL-10,
      transforming growth factor (TGF)-beta, prostaglandin E(2) (PGE(2)), and the
      proangiogenic modulator vascular endothelial growth factor (VEGF) decreased in
      response to DC-AdIL-7 treatment. Significant reduction in tumor burden in a model
      in which tumors develop in an organ-specific manner provides a strong rationale
      for further evaluation of DC-AdIL-7 in regulation of tumor immunity and its use
      in lung cancer genetic immunotherapy.

PMID- 14577916
TI  - Ectopic bone formation by human bone morphogenetic protein-2 gene transfer to
      skeletal muscle using transcutaneous electroporation.
AB  - Therapy using recombinant human bone morphogenetic protein-2 (rhBMP-2) is
      expected to promote bone healing and regeneration. Previous studies using protein
      or virus vectors for direct clinical application had problems, including a lack
      of efficiency, safety, and simplicity of the delivery system, and required an
      expensive protein, carrier matrix, or antigenic viral vector. In vivo gene
      transfer by electroporation is a simple and inexpensive method that only requires
      a plasmid and an electroporation device. Here, we created a plasmid-based human
      BMP-2 construct (pCAGGS-BMP-2) and examined the induction of bone in the skeletal
      muscle of rats after transferring different doses of this plasmid (25 microg, 100
      microg, and 400 microg) by transcutaneous electroporation (8 electrical pulses of
      100 V and 50 msec, in 1 to 5 sessions). First, we verified the gene transfer by
      transcutaneous electroporation using pCAGGS-lacZ. Next, the BMP-2 gene transfer
      and the production and localization of BMP-2 were identified by reverse
      transcription-polymerase chain reaction (RT-PCR), Western blots, and
      immunohistochemistry. Ectopic bone formation was verified by radiography,
      histologic and immunohistochemical analyses, and quantitative examination.
      Ectopic bone formation, consisting of active osteoblasts and osteoclasts, was
      observed in all rats treated with electroporation. Thus, transcutaneous
      electroporation with pCAGGS-BMP-2 induced ectopic bone formation in the skeletal
      muscle of rats. This supports the possibility of applying human BMP-2 gene
      transfer using transcutaneous electroporation clinically.

PMID- 14577917
TI  - Targeting a retroviral vector in the absence of a known cell-targeting ligand.
AB  - An important requirement for many gene therapy applications is to direct
      therapeutic genes specifically to target cells. Here we describe an improved
      vector targeting method that does not depend on the use of a known cell-targeting
      ligand. It entails screening a library of constitutively produced retroviruses
      with random amino acid substitutions in the cell-targeting region of the envelope
      proteins for their ability to mediate gene delivery to a target cell. By
      screening such a library on the ras-transformed 143B human cell line, we have
      isolated an envelope protein that preferentially targets 143B cells and 293T
      cells expressing the SV40 T antigen via a novel, unidentified receptor.
      Furthermore, retroviruses expressing the library-derived envelope protein can be
      concentrated by centrifugation. This is the first demonstration of a novel
      concept in vector targeting: the selection of productive retroviral entry via an
      alternate receptor with modified cellular tropism in the absence of a known cell
      targeting moiety. The method is, in principle, applicable even to cells that have
      not been well characterized, and therefore potentially suitable for targeting
      many diverse cell types.

PMID- 14577918
TI  - Biodistribution of oncolytic measles virus after intraperitoneal administration
      into Ifnar-CD46Ge transgenic mice.
AB  - In support of a proposed phase I clinical trial, we studied the biodistribution
      of virus-infected cells after intraperitoneal administration of oncolytic measles
      viruses to alpha/beta interferon-defective mice expressing human CD46 with human
      like tissue specificity. Various marker genes were employed, and green
      fluorescent protein proved to be most informative. Mesothelium and ovarian
      surface epithelium were remarkably resistant to infection, but infected
      peritoneal macrophages were present in abundance both in peritoneal lavage fluid
      and in the greater omentum, where they were heavily concentrated in "milky
      spots". Infected macrophages were also identified outside the peritoneal cavity,
      along the peritoneal fluid drainage pathway and in the spleen. Thus,
      diaphragmatic stomata, thoracic lymphatic vessels, and parathymic lymph nodes
      contained numerous measles-infected cells, as did the marginal zones of the white
      pulp of the spleen. Splenic marginal zone macrophages were the predominant
      targets of infection after intravenous administration of oncolytic measles
      viruses. When measles-infected peritoneal macrophages were adoptively
      transferred, they did not migrate beyond the confines of the peritoneal cavity,
      suggesting that, after intraperitoneal virus administration, the positive cells
      in thoracic lymphatics, parathymic lymph nodes, and spleen are nonmigratory cells
      transduced in situ by viral particles that have exited from the peritoneal
      cavity.

PMID- 14577919
TI  - A comparison of targeting performance of oncoretroviral versus lentiviral vectors
      on human keratinocytes.
AB  - The epidermis, like other rapidly renewing tissues, relies on a stem cell
      compartment to undergo constant regeneration. In order to develop realistic and
      long-lasting therapeutic approaches for some skin disorders, gene transfer to
      these critical cells must be obtained. While efficient retroviral ex vivo
      targeting and transgene integration in human keratinocytes is tightly dependent
      on proliferation, transferring genetic information to quiescent cells in culture
      also presents advantages, including the possibility of targeting putative dormant
      epidermal stem cells. In the present study we compared the efficiency of
      transduction achieved with a third-generation of human immunodeficiency virus
      (HIV)-based lentiviral vector to that obtained with a Moloney murine leukemia
      oncoretroviral vector (MLV) on proliferating and quiescent human keratinocytes
      growing in vitro in standard Rheinwald and Green cultures as well as in confluent
      organotypic cultures. Each viral vector contained the enhanced green fluorescent
      protein (EGFP) as a reporter gene. The lentiviral vector, but not the MLV vector,
      led to EGFP expression both in nondividing and proliferating epidermal cell
      populations in vitro. This feature was clearly evident when direct targeting of
      human keratinocytes, forming part of the epidermal component of an organotypic
      skin culture, was attempted. Keratinocytes modified by both MLV and the
      lentiviral vector allowed long-term regeneration of genetically engineered human
      skin on the backs of immunodeficient nonobese diabetic/severe combined
      immunodeficiency disorders (NOD/SCID) mice. However, EGFP transgene expression in
      the context of the MLV (long-terminal repeat [LTR]-driven) or lentiviral vector
      (cytomegalovirus [CMV]-driven) demonstrated clear differences both in
      quantitative terms and in the in vivo localization pattern.

PMID- 14577920
TI  - A therapy modality using recombinant IL-12 adenovirus plus E7 protein in a human
      papillomavirus 16 E6/E7-associated cervical cancer animal model.
AB  - Interleukin (IL)-12 has been reported to induce cellular immune responses for
      protection against tumor formation. Here we investigate the utility of adenoviral
      delivery of IL-12 as an adjuvant for a human papillomavirus E7 subunit vaccine in
      a mouse tumor challenge model. Direct intratumoral injection of AdIL-12 resulted
      in a significant suppression of tumor growth compared to the control group.
      Injection of E7 protein into either a tumor site or the distance site along with
      AdIL-12 further enhanced antitumor effects significantly higher than either AdIL
      12 or E7 injection alone. This combined injection resulted in complete regression
      of 9-mm-sized tumor in 40% of animals as well as lasting antitumor immunity
      against tumor recurrence. We also evaluated immune responses induced by these
      injections. AdIL-12 plus E7 enhanced E7-specific antibody responses significantly
      higher than AdIL-12 or E7 injection. In particular, the production level of
      interferon (IFN)-gamma from E7-specific CD4(+) T cells was similar between AdIL
      12 group and AdIL-12 + E7 group. However, IFN-gamma production from E7-specific
      CD8(+) T cells was the most significant when injected with AdIL-12 + E7. This was
      consistent with intracellular IFN-gamma staining levels of CD8(+) T cells,
      suggesting that AdIL-12 + E7 injection enhances antitumor immunity in the human
      papillomavirus (HPV) 16 tumor model through increased expansion of the cytotoxic
      T-lymphocyte (CTL) subset. This enhanced protection appeared to be mediated by
      CD8(+) T cells, as determined by in vivo T-cell subset deletion. Thus, these
      studies demonstrate that E7 vaccines can induce CTL responses responsible for
      antitumor effects in the presence of IL-12 delivered via adenovirus vectors. This
      likely provides one additional approach for immune therapy against cervical
      cancers.

PMID- 14577921
TI  - Glucose-responsive hepatic insulin gene therapy of spontaneously diabetic BB/Wor
      rats.
AB  - Hepatic insulin gene therapy (HIGT) ameliorates hyperglycemia in multiple rodent
      models of diabetes mellitus, with variable degrees of glucose control. We
      demonstrate here that adenoviral delivery of a glucose-regulated transgene into
      rat hepatocytes produces near-normal glycemia in spontaneously diabetic BB/Wor
      rats without administration of exogenous insulin. We compared growth, glycemia,
      counterregulatory hormones, and lipids in HIGT-treated diabetic rats to
      nondiabetic rats and diabetic rats treated with either insulin injections or
      sustained-release insulin pellets. HIGT-treated rats achieved near-normal blood
      glucose levels within 1 week and maintained glycemic control for up to 3 months.
      Rats treated with sustained release insulin implants had similar blood sugars,
      but more hypoglycemia and gained more weight than HIGT-treated rats. HIGT-treated
      rats normalized blood glucose within 2 hr after a glucose load, and tolerated a
      24-hr fast without hypoglycemia. HIGT treatment suppressed ketogenesis similarly
      to peripheral insulin. However, glucagon levels and free fatty acids were
      increased in HIGT-treated rats compared to either nondiabetic controls or rats
      treated with exogenous insulin. In addition to extending successful application
      of HIGT to a rat model of autoimmune diabetes, these findings emphasize the
      relative contribution of hepatic insulin effect in the metabolic stabilization of
      diabetes mellitus.

PMID- 14577922
TI  - Ad-mTERT-delta19, a conditional replication-competent adenovirus driven by the
      human telomerase promoter, selectively replicates in and elicits cytopathic
      effect in a cancer cell-specific manner.
AB  - Human telomerase reverse transcriptase (hTERT), the catalytic subunit of
      telomerase, functions to stabilize telomere length during chromosomal
      replication. Previous studies have shown that hTERT promoter is highly active in
      most tumor and immortal cell lines but inactive in normal somatic cell types. The
      use of wild-type hTERT promoter, however, may be limited by its inability to
      direct high level and cancer cell-specific expression necessary for effective
      targeted gene therapy. To improve cancer cell specificity and the strength of the
      hTERT promoter, a modified hTERT, m-hTERT promoter was generated in which
      additional copies of c-Myc and Sp1 binding sites were incorporated adjacent to
      the promoter. As assessed using relative lacZ expression, hTERT and m-hTERT
      promoter activity was significantly upregulated in cancer cells but not in normal
      cells, and within these upregulated cancer cells, m-hTERT promoter strength was
      substantially higher than that of the wild-type hTERT. Next, to restrict viral
      replication to tumor cells, a conditional replication-competent adenoviruses, Ad
      TERT-Delta19 and Ad-mTERT-delta19 were generated in which the E1A gene, which is
      essential for viral replication, was placed under the control of the hTERT and m
      hTERT promoter, respectively. While the wild-type Ad-TERT-delta19 replicated in
      and induced cytopathic effect in cancer and in some normal cell lines, Ad-mTERT
      delta19 enhanced viral replication and cytopathic effect only in cancer cells.
      Furthermore, the growth of established human cervical carcinoma in nude mice was
      significantly suppressed by intratumoral injection of Ad-mTERT-delta19. Taken
      together, present results strongly suggest that the use of the m-hTERT promoter
      is not only useful in the regulation of therapeutic gene expression but also that
      replication-competent oncolytic adenovirus under the control of the m-hTERT
      promoter may be a new promising tool for the treatment of human malignancies.

PMID- 14577923
TI  - Prospects for delivery of recombinant angiostatin by cell-encapsulation therapy.
AB  - Implantation of encapsulated nonautologous cells that have been genetically
      modified to secrete proteins with tumor suppressor properties represents an
      alternative nonviral strategy to cancer gene therapy. We report an approach to
      raise the yield of recombinant proteins from encapsulated cells substantially. We
      hypothesized that by optimizing the encapsulation procedure, the production
      efficacy from the encapsulated cells could be increased. HEK 293 EBNA cells were
      genetically engineered to produce angiostatin. Encapsulation was performed by
      varying bead size, cellular density, homogeneity, and ion composition of the gel.
      The morphology and viability of the cells and the release of angiostatin were
      studied. Computer software was developed for three-dimensional imaging and
      quantification of cell viability. Angiostatin production was assessed at 3, 6,
      and 11 weeks using enzyme-linked immunosorbent assay (ELISA). Inhomogeneous gels
      facilitated cell growth and viability. The most efficient inhomogeneous
      microcapsules were generated by reducing the size and cellular density of the
      beads. The viability and the production of angiostatin were 3 to 5 times higher
      than in the homogeneous capsules. Significant amounts of viable cells were
      present in both homogeneous and inhomogeneous beads after 6 months of culture.
      The stability of the alginate matrix was greatly enhanced by gelling in the
      presence of barium. In conclusion, the viability and production efficacy of
      recombinant angiostatin from alginate-encapsulated cells can be increased
      considerably by optimizing the encapsulation procedure. The development of such
      optimized microcapsules brings cell-encapsulation therapy further towards
      clinical use in cancer therapy.

PMID- 14577924
TI  - Correction of the dystrophic phenotype by in vivo targeting of muscle progenitor
      cells.
AB  - Successful gene therapy for most inherited diseases will require stable
      expression of the therapeutic gene. This can be addressed with integrating or
      self-replicating viruses by targeting postmitotic cells that have a long lifetime
      or stem cells that can replenish defective tissue with corrected cells. In this
      study, we explore the possibility of targeting a muscle stem cell population in
      situ through in vivo administration of vector. To develop this concept, we
      selected a mouse model of muscular dystrophy (mdx mice) that undergoes rapid
      turnover of muscle fibers. In vivo targeting of muscle progenitor cells, notably
      satellite cells, with a pseudotyped lentiviral vector encoding the minidystrophin
      restores dystrophin expression and provides functional correction in skeletal
      muscle of mdx mice. This study shows that progenitor cells can be genetically
      engineered in vivo and subsequently proliferate into terminally differentiated
      tissue carrying the genetic graft in a way that stably corrects function.

PMID- 14577925
TI  - Angiogenic responses of vascular endothelial growth factors in periadventitial
      tissue.
AB  - Recent discovery of new members of the vascular endothelial growth factor (VEGF)
      family has generated much interest as to which members may be best suited for
      therapeutic angiogenesis in various tissues. In this study we evaluated
      angiogenic responses of the different members of the VEGF family in vivo using
      adenoviral gene transfer. Adenoviruses (1 x 10(9) plaque-forming units [pfu])
      encoding for VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-C(deltaNdeltaC) and VEGF
      D(deltaNdeltaC) (deltaNdeltaC are proteolytically cleaved forms) were transferred
      locally to the periadventitial space of the rabbit carotid arteries using a
      collar technique that allows efficient local transfection of the periadventitial
      tissue. Expression of the transfected VEGFs was confirmed by immunohistochemistry
      and reverse transcription-polymerase chain reaction (RT-PCR). Seven days after
      the gene transfer maximum neovessel formation was observed in VEGF-A-, VEGF-D-,
      and VEGF-D(deltaNdeltaC)-transfected arteries. VEGF-C(deltaNdeltaC) also showed
      angiogenic activity whereas VEGF-B was not effective in inducing angiogenesis.
      Pericytes were detected around the neovessels, which also frequently showed the
      presence of intraluminal erythrocytes. Infiltration of inflammatory cells in
      response to VEGF-D and VEGF-D(deltaNdeltaC) was less prominent than that caused
      by other VEGFs. In line with the absence of lymphatics in the normal carotid
      arteries no significant evidence of lymphatic vessel formation was seen in
      response to any of the studied VEGFs in the periadventitial space. The results
      help to define possibilities for local angiogenic therapy around blood vessels
      and support the concept that angiogenic effects may be tissue-specific and depend
      both on the growth factor ligands and the target tissues. It is concluded that
      VEGF-A, VEGF-D, and VEGF-D(deltaNdeltaC) are the best candidates for therapeutic
      angiogenesis when delivered around large arteries.

PMID- 14577926
TI  - Long-term neuronal effects and disposition of ectopic preproNGF gene transfer
      into the rat septum.
AB  - Although NGF gene therapy has been proposed to treat age- or disease-related
      brain cholinergic decline, little is known about the ectopic expression or
      function of this trophic factor after transduction in the brain especially over
      long intervals. The neuron-targeting, recombinant adeno-associated virus serotype
      2 (rAAV2) vector was used to express mouse NGF with C-terminal myc-tag in septum
      using a full-length preproNGF sequence. While the predominant form of endogenous
      NGF immunoreactivity in septum was 31 kd of proNGF, almost all of the ectopic NGF
      immunoreactivity attributable to the rAAV2-mediated transduction in this region
      was recovered as mature NGF. Transgene expression was found in both cholinergic
      and GABAergic neurons, with the number of transduced neurons dependent on vector
      dose. To determine the long-term effects of this NGF-expression on neuron
      function, fimbria-fornix (FF) lesions were conducted 6 months after NGF gene
      transfer. NGF gene transfer attenuated the lesion-induced loss of septal
      cholinergic but not GABAergic neurons, indicating that long-term expression did
      not eliminate this response, which has been noted over short intervals. The
      effects and dose dependency of NGF gene delivery on neuroprotection and
      neurotrophism were also examined. NGF transduction increased cholinergic cell
      size in the septum, but required a higher vector dose than neuroprotection. These
      results reveal potential long-term benefits as well as concerns for genetically
      modifying septal NGF gene expression to preserve neuronal viability and function.

PMID- 14577927
TI  - Telomerase alone extends the replicative life span of human skeletal muscle cells
      without compromising genomic stability.
AB  - Continuous cycles of muscle fiber necrosis and regeneration are characteristic of
      the muscular dystrophies, and in some cases this leads to premature replicative
      senescence of myoblasts in vitro. The molecular mechanism of senescence in human
      myoblasts is poorly understood but there is evidence to suggest that telomeric
      attrition may be one of the ways by which this is achieved. We report here, for
      the first time, the extension of normal human skeletal muscle cell replicative
      life span by the reconstitution of telomerase activity. The telomerase-expressing
      cells show no features of transformation in vitro and have stable genomes with
      diploid karyotypes, do not express exceptionally high levels of c-myc and have
      wild-type, unmethylated CDKN2A genes. In vivo, they regenerate to repair muscle
      injury in immunosuppressed RAG-1 mice. This work suggests that telomerase
      expression to repair short telomeres may aid the expansion of diploid human
      muscle cells and consequently attempts at gene therapy for muscle diseases.

PMID- 14577928
TI  - Correction of bleeding diathesis without liver toxicity using arenaviral
      pseudotyped HIV-1-based vectors in hemophilia A mice.
AB  - Hemophilia A is an inheritable X-linked bleeding disorder most frequently
      occurring as a consequence of genetic alterations within the factor VIII (FVIII)
      gene. In the present study, pseudotyped human immunodeficiency virus type 1 (HIV
      1)-derived lentivectors expressing hFVIII were assessed for the ability to
      correct the hemophilia A phenotype in FVIII knockout mice. Therapeutic levels of
      plasma hFVIII (1-7 ng/mL) were detected in C57B1/6 mice (4-5 weeks old) after
      portal vein administration of hFVIII-expressing lentivectors pseudotyped with the
      rhabdoviral vesicular stomatitis viral G protein (VSV-G). More importantly,
      transduction of hemophilia A mice with FVIII expressing lentivectors resulted in
      transient correction of the bleeding diathesis phenotype. Moreover, the use of
      alternate viral pseudotypes based on the lymphocytic choriomeningitis virus
      (LCMV) resulted in similar circulating levels of FVIII. Interestingly, similar
      doses of LCMV-pseudotyped lentiviral vectors resulted in minimal systemic or
      hepatic injury as measured by plasma alanine transferase (ALT), aspartate
      transferase (AST), and tumor necrosis factor (TNF)-alpha compared to the more
      commonly used envelope, VSV-G. In summary, these studies demonstrated both the
      potential merit of lentivectors in terms of correcting monogenic inherited
      disorders, and also the importance of using alternate pseudotypes, such as LCMV,
      to safely transfer therapeutic genes in vivo without producing adverse effects.

PMID- 14577929
TI  - [Physical, psychological, emotional, and sexual violence during pregnancy as a
      reproductive-risk predictor of low birthweight in Costa Rica].
AB  - OBJECTIVE: To determine the prevalence of physical, psychological, emotional, and
      sexual violence during pregnancy and the association that that violence has with
      low birthweight. METHODS: For 118 women who gave birth between September 1998 and
      November 1999 we explored the violence that they had suffered during their
      pregnancy. All the women were residents of Finca San Juan, a low-income urban
      settlement in the Rincon Grande de Pavas section of San Jose, Costa Rica. We used
      a previously validated questionnaire with closed questions. A multiple linear
      regression model was used to adjust the average weights of the newborns according
      to the characteristics of the mother: age, years of schooling, marital status,
      desire for the pregnancy, harmful habits (smoking, drinking alcohol), number of
      previous pregnancies and childbirths, birth interval, physical stature, total
      increase in weight during the pregnancy, and illnesses during the gestation. A
      logistic regression model was used to measure the direct effect of violence on
      low birthweight, and a nonparametric method was used to calculate the
      attributable fraction among the exposed women. RESULTS: The newborns of the
      mothers who suffered acts of violence weighed on average 449.4 g less that the
      newborns of the women who had not been exposed to acts of violence (P < 0.001).
      The mothers who suffered acts of violence were three times as likely to have a
      newborn with low birthweight (95% confidence interval: 1.39 to 8.10). The
      variables that were most closely associated with low birthweight were violence
      suffered by the mother (direct association) and the mother's weight gain during
      pregnancy (inverse relation). CONCLUSIONS: Our results indicate the need to
      investigate this subject more deeply, to train health workers concerning violence
      toward women as a reproductive-risk factor, and to form groups of experts on this
      subject to develop specialized protocols for the early identification of pregnant
      women subject to violence.

PMID- 14577930
TI  - Behavioral problems and tobacco use among adolescents in Chile.
AB  - OBJECTIVE: To examine the association between behavioral problems and tobacco
      smoking among adolescent students in Chile. METHODS: Data were drawn from a study
      that included questionnaire surveys of 46 907 school-attending adolescents in all
      13 of the administrative regions of Chile. Assessments were based on an adapted,
      Spanish-language version of the Drug Use Screening Inventory. The conditional
      form of the logistic regression model was used for analysis, with matching of
      students on individual schools, and with further statistical adjustments for sex,
      age, and selected risk factors. RESULTS: The prevalence of tobacco smoking among
      the adolescents was very high across all of Chile, with a level between 56% and
      65% in each of the 13 regions. The estimated odds of tobacco use in youths at the
      highest level of behavioral problems was about twice that for youths at the
      lowest levels, both before and after controlling for sex, age, lack of
      participation in recreational activities, level of irritability, and levels of
      problems with school, family attention, and mental health. CONCLUSIONS: These
      findings help to complement and complete the evidence of prior studies on tobacco
      smoking among adolescents with behavior problems, including recent research on
      Central American youths. Although the magnitude of observed associations in Chile
      was not as great as that for the associations found in Central America, both the
      strength of these associations and their statistical significance were observed
      throughout Chile. This is the first study in Chile on potentially causal
      relationships such as these.

PMID- 14577931
TI  - [An overview of hepatitis B in Brazil and in the state of Santa Catarina].
AB  - OBJECTIVE: To provide an overview of hepatitis B infection in Brazil overall, in
      the South of Brazil, and in the state of Santa Catarina (in southeastern Brazil)
      for the period of 1996 through 2002, taking into consideration such
      epidemiological aspects as age and sex. SOURCE OF DATA: Data were obtained
      through a literature review and by consulting with Brazil's National Health
      Foundation and with Santa Catarina's Department of Epidemiological Surveillance.
      RESULTS: In Brazil, from 1996 through 2000, hepatitis B was the second most
      prevalent type of viral hepatitis (25%), with hepatitis A leading in terms of the
      proportion of cases (43%). In Santa Catarina there was a predominance of
      hepatitis B in relation to other types of hepatitis from 1997 through 2001. In
      both Brazil and Santa Catarina there was a larger number of cases among males
      than among females. In terms of age, the highest incidence was found among those
      20 to 49 years old in Santa Catarina and among those over 30 for Brazil overall.
      The South of Brazil was the country's region with the highest incidence of
      hepatitis B from 1997 through 1999. In Santa Catarina the largest number of cases
      from 1996 through 2002 occurred in the southern part of the state, followed by
      the northeastern and far western sections of the state. CONCLUSIONS: The number
      of cases of hepatitis B is still growing in Brazil, and it is important to
      consider that underreporting may have affected the results described in this
      study. Throughout Brazil, vaccination should be extended to include adolescents
      in regions that have a moderate to high incidence of hepatitis B.

PMID- 14577932
TI  - Perceptions and experiences of violence among secondary school students in urban
      Jamaica.
AB  - OBJECTIVE: To obtain information on the perceptions and experiences of violence
      among secondary school students in Kingston, Jamaica, and its environs. METHODS:
      Data collection was carried out from September through December 1998. Two
      researchers administered questionnaires in 11 randomly selected secondary
      schools, to a total of 1 710 students who were in either grade 7 or grade 9 and
      who were aged 9-17 years old (mean of 13.2 years). Frequency distributions of the
      responses were compared by gender, age, grade level, socioeconomic status, and
      school type. RESULTS: Seventy-five percent of the students thought that someone
      who was reluctant to fight would be "picked on" more, 89% thought it generally
      wrong to hit other people, and 91% thought it wrong to insult other people.
      Eighty-four percent knew of students who carried knives or blades from such items
      as a scalpel or a utility knife to school, and 89% were worried about violence at
      school. Thirty-three percent had been victims of violence, and 60% had a family
      member who had been a victim of violence. Eighty-two percent thought that violent
      television shows could increase aggressive behavior. Factor analysis of selected
      responses was carried out, yielding five factors: neighborhood violence, school
      violence, perceptions of acceptable behaviors, level of concern about violence,
      and general experiences and perceptions of violence. The factors varied with
      gender, age, grade level, socioeconomic status, and school type. CONCLUSIONS:
      These results will help focus interventions aimed at reducing violence, provide a
      baseline for later comparisons of perceptions and experiences of violence, and
      offer a basis for comparing the experiences of young people in urban Jamaica with
      those of young persons elsewhere.

PMID- 14577933
TI  - [National neuroepidemiological study in Colombia (EPINEURO)].
AB  - OBJECTIVE: To determine the prevalence of eight neurological problems-migraine,
      cerebrovascular disease, Parkinson's disease, peripheral neuropathy, disorders of
      neurological development, epilepsy, dementia, and sequelae of head trauma-in
      Colombia as a part of the National Neuroepidemiological Study (EPINEURO).
      METHODS: A cross-sectional survey was carried out in two phases between September
      1995 and August 1996. In the first phase persons who might be suffering from a
      neurological disease were identified, and in the second phase a specific
      diagnosis was made. A sample of 8 910 people were examined, distributed in
      proportion to the population in each of the five geographical areas of Colombia
      (central, southwest, northwest, eastern, and Caribbean coast). The evaluation was
      done using a modified version of the neuroepidemiology protocol of the World
      Health Organization, along with a simplified physical examination. With the
      patients with possible dementia a neuropsychological examination designed for
      this study was used in order to thoroughly examine the cognitive aspects analyzed
      in the initial mental screening. The scales of Hachinski, Yesavage, and Blessed
      and the diagnostic criteria of the NINCDS-ADRDA were used for Alzheimer's
      disease; the NINDS-AIREN criteria for dementia of vascular origin; and the DSM-IV
      criteria for all types of dementia. A survey was conducted in order to determine
      if there were sequelae of head trauma. Persons 12 years old or older were
      evaluated by an adult neurologist and those under 12 years old by a pediatric
      neurologist. The prevalences of neurological disorders were calculated by age and
      sex, for each region and also for the entire country, with 95% confidence
      intervals (CIs). RESULTS: The prevalence per 1 000 population for the disorders
      investigated was: migraine, 71.2 (95% CI: 65.5 to 76.8); disorders of
      neurological development, 46.1 (95% CI: 35.5 to 58.9); cerebrovascular disease,
      19.9 (95% CI: 14.3 to 27.4); dementia, 13.1 (95% CI: 8.5 to 19.3); epilepsy, 10.3
      (95% CI: 8.5 to 13.0); peripheral neuropathy, 8.5 (95% CI: 6.8 to 10.7); sequelae
      of head trauma, 6.4 (95% CI: 5.0 to 7.8); and Parkinson's disease, 4.7 (95% CI:
      2.2 to 8.9). In all those cases except head trauma the prevalence was higher
      among women than among men. CONCLUSIONS: These results make it possible to design
      more up-to-date health policies aimed at achieving more effective prevention,
      better control, and more adequate treatment of neurological disorders in
      Colombia. The easy application of these surveys and the low cost of this type of
      research make this methodology ideal for countries with shortages of specialized
      personnel.

PMID- 14577934
TI  - [The association between oral manifestations and the socioeconomic and cultural
      characteristics of HIV-infected children in Brazil and in the United States of
      America].
AB  - OBJECTIVES: This study had two objectives: (1) to investigate the socioeconomic
      and cultural characteristics of HIV-infected children and their families in
      relation to the presence of oral manifestations of AIDS and (2) to identify the
      most frequent oral manifestations of AIDS in the sample of children studied.
      METHODS: The sample consisted of a total of 184 children - both boys and girls -
      from 0 to 13 years old. The children were receiving care at two hospitals in the
      city of Porto Alegre, Brazil (the Hospital de Clinicas de Porto Alegre and the
      Hospital Sao Lucas da Pontificia Universidade Catolica), and at Stony Brook
      University Hospital, which is in the state of New York, United States. Data were
      analyzed using the chisquare test, Student's t test, and analysis of variance.
      RESULTS: Of the 184 patients, 117 of them (63.59%) were receiving care at the
      Hospital de Clinicas de Porto Alegre, 26 (14.13%) at the Hospital Sao Lucas, and
      41 (22.28%) at Stony Brook University Hospital. In the Brazilian sample (the two
      hospitals in Porto Alegre) 42.66% of the children were living with their natural
      parents (mostly with the mother), while in the United States 56.10% of the
      children were living with foster families. Concerning income, 39.86% of the
      Brazilian families had a monthly income ranging from US$ 180 to US$ 450, and
      33.57% had no income or did not provide information. With the United States
      sample, we were not allowed to ask about income, but all the families were
      classified by the social workers as having a monthly income below US$ 1 000. HIV
      was acquired through vertical transmission by 97.20% of the Brazilian children
      and by 97.56% of the children in the United States sample. Oral manifestations
      were more frequent in the Brazilian children (72.73%) than in the children in the
      United States sample (53.66%) (P = 0.01). CONCLUSIONS: The frequency of oral
      manifestations in the samples in both Brazil and the United States was influenced
      by socioeconomic and cultural conditions, family structure and income, access to
      information concerning AIDS, and adherence to treatment.

PMID- 14577935
TI  - [Factors associated with stages of behavior change in Cuban smokers].
AB  - OBJECTIVE: To describe the distribution of Cuban smokers in the first two stages
      of the process of behavior change (precontemplation (that is, no desire to quit
      smoking) and contemplation (thinking about quitting)), the characteristics of
      these smokers, and the relationship between these characteristics and some
      variables of interest. METHODS: The First National Survey of Risk Factors and
      Chronic Non-communicable Disease Prevention Activities was carried out in Cuba in
      1996. As a part of that Survey, a probability sample was selected using three
      stage clustering, with stratification of the primary units, which were the census
      districts in the 14 provinces and 169 municipalities that make up the country.
      The census districts were selected in proportion to their number of dwellings. A
      total of 4 835 smokers 15 years old or older were selected to answer a
      questionnaire on sociodemographic variables and smoking-related behaviors. The
      sociodemographic variables included age, sex, skin color, level of schooling
      completed, and work status (working, looking for work, retired, housewife, or
      student). The smoking-related behaviors included knowledge of tobacco's harmful
      effects on health, age when smoking began, number of cigarettes smoked daily,
      willingness to give up the habit, and the number of attempts made to quit
      smoking. The questionnaire information made it possible to place the smokers in
      one or the other of the two initial stages of smoking behavior change. The
      probability of being in the precontemplation stage was modeled through logistic
      regression. The standardized coefficients that the model produced were used to
      calculate the weight of the explanatory variables included in the model. To
      calculate the estimates and their errors, the SAS 6.12 and SUDAAN 7.5 statistical
      software packages were used, taking into account the complex design of the
      sample. The level of significance was set at 0.05. RESULTS: We found that 46.4%
      of the smokers surveyed were in the precontemplation stage, and 53.6% were in the
      contemplation stage. Women were more prepared to quit the habit than were men.
      The more formal the education that a person had, the stronger was the desire to
      quit smoking. Persons who were retired were the ones least likely to be
      considering giving up smoking. The probability of being in the precontemplation
      stage decreased with an increase in the age of beginning to smoke, the number of
      cigarettes smoked daily, and the number of attempts made to quit smoking.
      CONCLUSIONS: The proportion of Cuban smokers in the contemplation stage places
      the country in a favorable position for developing effective smoking prevention
      interventions. The majority of the factors identified (age when smoking began,
      number of cigarettes consumed daily, and number of attempts to give up the habit)
      can be modified through preventive actions. Identifying the stages in the process
      of change and the factors linked to them are necessary for designing and
      implementing effective smoking prevention and control programs.

PMID- 14577936
TI  - Abortion, contraceptive use, and adolescent pregnancy among first-year medical
      students at a major public university in Mexico City.
AB  - OBJECTIVE: If properly trained, medical students could become future opinion
      leaders in health policy and could help the public to understand the consequences
      of unwanted pregnancies and of abortions. The objective of this study was to
      analyze the frequency of unwanted pregnancies and induced abortions that had
      occurred among women who were first-year medical students at a major public
      university in Mexico City and to compare the experiences of those women with the
      experiences of the general population of Mexican females aged 15 to 24. METHODS:
      In 1998 we administered a cross-sectional survey to all the first-year medical
      students at the National Autonomous University of Mexico, which is the largest
      university in Latin America. For this study we analyzed 549 surveys completed by
      female students. RESULTS: Out of the 549 women, 120 of them (22%) had been
      sexually active at some point. Among those 120 sexually active students, 100 of
      them (83%) had used a contraceptive method at some time, and 19 of the 120 (16%)
      had been pregnant. Of those 19 women who had been pregnant, 10 of them had had an
      illegal induced abortion (in Mexico, abortions are illegal except under a small
      number of extenuating circumstances). The reported abortion rate among the female
      medical students, 2%, was very low in comparison with the 11% rate for women of
      similar ages in the Mexican general population. CONCLUSIONS: The lower incidence
      of abortion among the female medical students indicates that when young Mexican
      women have access to medical information and are highly motivated to avoid
      unintended pregnancy and abortion, they can do so.

PMID- 14577941
TI  - Assessing an Internet health information site by using log analysis: the
      experience of the National Cancer Institute of Brazil.

PMID- 14577942
TI  - [New treatment guidelines for persons with HIV infection. 2003].

PMID- 14577943
TI  - Biomechanical stresses in computer-aided design and in data entry.
AB  - A study of the risk factors of musculoskeletal disorders (MSDs) of the upper
      limbs was carried out on 2 populations, 1 performing a computer-aided design
      (CAD) task and the other performing a data entry task. A questionnaire on MSD
      complaints and working life was completed by a sample of each population.
      Biomechanical measurements of the forces, the angles, and the repetitiveness of
      movements of the upper limbs were carried out on some operators in each sample.
      It emerged that complaints of the upper limbs seem to be linked to the use of
      input devices. The grip forces exerted when using the keyboard and mouse were
      higher in CAD than in data entry.

PMID- 14577944
TI  - Application of neural networks in active noise reduction systems.
AB  - Active noise reduction systems based on a control unit in the form of a finite
      impulse response filter assume the linearity of every single component. Neural
      networks, which have so far been seldom used in this field, are a kind of a
      filter with the ability to project nonlinear characteristics of an active noise
      reduction system. This paper presents some simulation research studies of active
      noise reduction systems based on neural networks. Also presented are results of
      the operation of systems with different levels of complexity as well as the
      influence of different parameters of a neural network and of the system itself on
      those results.

PMID- 14577946
TI  - Resistance of medical gloves to permeation by methyl methacrylate (MMA), ethylene
      glycol dimethacrylate (EGDMA), and 1,4-butanediol dimethacrylate (1,4-BDMA).
AB  - Gloves afford hand protection by minimizing skin contact. The effectiveness of
      medical gloves to protect against permeation of the monomers, methyl methacrylate
      (MMA), ethylene glycol dimethacrylate (EGDMA), and 1,4-butanediol dimethacrylate
      (1,4-BDMA), was assessed focusing on permeation rates and degradation of glove
      materials caused by monomer contact. Fifteen different brands of gloves were
      tested using a European Standard procedure. Surface images of glove materials
      before and after exposure to the monomer mixture were obtained using a scanning
      electron microscope. The standard is not applicable as the only method for
      estimating the safety of gloves, but it is useful as guideline together with the
      cumulative permeation of acrylic monomers. Monomer contact on the outside
      resulted in substantial swelling of most glove materials, and structure changes
      of the inside surface.

PMID- 14577945
TI  - Evaluation and quantification of manual materials handling risk factors.
AB  - This study investigated the ability of the Revised NIOSH Lifting Equation (RNLE)
      to measure the risk of low back injury as verified by employee health outcomes.
      In addition, several basic risk factors and combinations of risk factors presumed
      related to low back disorders were explored. The RNLE was modified to allow
      analysis of one-handed and two-handed, asymmetric lifts. Predictive performance
      was not changed. Simplifying the RNLE by removing several variables did not
      significantly reduce the RNLE's predictive performance. These modifications to
      the RNLE show promise for increasing both the usability and utility of the RNLE.

PMID- 14577947
TI  - Adsorption air cleaning from ozone.
AB  - Not much has been written about air cleaning from ozone. The aim of this paper
      was to demonstrate the possibility of adsorption air cleaning from ozone. The
      second aim was to investigate the dependence of the efficiency of ozone removal
      from the air on the height of the adsorber layer and on concentrations of ozone,
      and to obtain empirical formulas for calculating the efficiency of ozone
      treatment. Equipment for air cleaning from ozone and nitrogen and sulphur
      dioxides is suggested.

PMID- 14577948
TI  - Test method for retractable type fall arresters designed for horizontal use.
AB  - Retractable type fall arresters are designed to protect against falls from a
      height of people who need freedom of vertical movement. The practice of fall
      protection shows that the devices are also used to protect people who work on
      flat roofs. This application creates quite different operating conditions for the
      devices. In some situations those conditions can be dangerous for users. The
      article presents a theoretical analysis of phenomena occurring during a fall
      arrest with retractable type fall arresters arranged horizontally. The analysis
      was verified with laboratory tests. The article presents a proposal for the
      construction of a test stand and a test method for estimating retractable type
      fall arresters intended for horizontal use.

PMID- 14577949
TI  - Emission of dust and gases in tubular cored wire welding of steel.
AB  - The emission of dusts and gases, which are generated during tubular cored wire
      welding and which are hazardous to health and the environment, were studied.
      Tests included various kinds of tubular electrode wires used for welding steel,
      that is, rutile flux cored wires, basic flux cored wires, and metal cored wires
      for welding unalloyed, low-alloy, and high-alloy steels as well as self-shielded
      flux cored wires used for welding low-alloy steels. The research results make it
      possible to assess the influence of the type of wire and welding conditions on
      the emission volume and to compare chemical hazards generated during tubular
      cored wire welding with those typical for other arc welding processes.

PMID- 14577950
TI  - Noise emission--a part of risk assessment with a view to machine safety.
AB  - For specific machinery groups standards on International Organization for
      Standardization (ISO) or European Committee for Standardization (CEN) levels
      describe safety aspects, technical data, or test methods. Problems with the
      implementation of noise aspects in safety standards are discussed. The reduction
      of emissions from machinery (noise, vibration, radiation, hazardous substances)
      has to date clearly been almost neglected, due, it seems, to the unsuitable
      approach of classical risk reduction. The concepts of the ISO/IEC Guide 51:1999,
      Standards No. EN 292, and the Directive of the European Parliament and the
      Council 98/37/EC (the so-called Machinery Directive) to reduce risks are compared
      and specific requirements to safety standards according to emission, especially
      of noise, are presented.

PMID- 14577951
TI  - Opportunities and challenges.

PMID- 14577952
TI  - Antiviral therapy in children with varicella zoster virus and herpes simplex
      virus infections.
AB  - A small number of antiviral drugs are available for the treatment of varicella
      zoster virus (VZV) and herpes simplex virus (HSV) infections in children. This
      review presents pharmacokinetic data on the following selected antiviral agents:
      aciclovir, valaciclovir, famciclovir, cidofovir and foscarnet. Support and
      current recommendations for the treatment of selected VZV and HSV infections in
      children will also be reviewed.

PMID- 14577953
TI  - Herpes zoster in the immunocompetent patient: management of post-herpetic
      neuralgia.
AB  - Post-herpetic neuralgia (PHN) is the most common complication of herpes zoster
      (HZ, shingles), particularly in the elderly and those with severe acute phase
      symptoms. Unless or until varicella vaccination reduces the incidence of HZ and
      attenuates the risk and/or severity of complications, PHN will continue to result
      in patient suffering and remain a significant cause of healthcare and social
      support resource consumption. There have been useful advances in PHN management
      (e.g. use of the anticonvulsant gabapentin and topical local anaesthetic
      patches), but some cases remain intractable. Prevention is an important strategy,
      and antiviral drugs, while not totally effective, provide the most accepted
      method. Other acute interventions require further evaluation (nerve blocks, acute
      phase use of tricyclic antidepressants or anticonvulsants). As prevention of PHN
      requires early recognition and prompt management of at-risk patients presenting
      with acute HZ, public education and provision of information to relevant
      healthcare personnel are important. This article discusses issues relevant to PHN
      management and prevention, and provides a review of the pertinent literature.

PMID- 14577954
TI  - New antiviral drugs that target herpesvirus helicase primase enzymes.
AB  - Herpesviruses have infected the majority of the world's population and the
      associated diseases have plagued humanity since ancient times. Nine causative
      human herpesviruses have been identified so far. The first antiviral drug was
      launched in 1962, and since then several drugs for treating herpesvirus
      infections, which work via different mechanisms, have been developed. Current
      treatments abrogate or suppress disease symptoms but are not curative. A vaccine
      based on the OKA strain of varicella zoster virus is being marketed, but to date
      no therapeutic or prophylactic herpes vaccinations that can treat or stop spread
      of other herpes diseases are available. Herpes simplex virus causes mucocutaneous
      infections such as herpes genitalis (genital herpes) and herpes labialis (cold
      sores), the potentially sight-impairing herpetic eye disease, and life
      threatening herpes encephalitis or disseminated disease. Recently, reports of
      helicase primase inhibitors, the first non-nucleosidic antiviral compounds, which
      are superior in pre-clinical profile to current herpes simplex virus medication,
      have been published. This review summarizes the data on helicase primase
      inhibitors and compares their pre-clinical profile with the established medical
      standard.

PMID- 14577955
TI  - No significant analgesic benefit of adding lidocaine 2% to aciclovir 5% cream as
      treatment of episodes of herpes labialis.

PMID- 14577972
TI  - Cellular uptake of a dexamethasone palmitate-low density lipoprotein complex by
      macrophages and foam cells.
AB  - To evaluate the utility of a dexamethasone palmitate (DP)-low density lipoprotein
      (LDL) complex to transport drug into foam cells, the cellular uptake of DP-LDL
      complex by macrophages and foam cells was examined. The DP-LDL complex was
      prepared by incubation with DP and LDL, and the DP-LDL complex and murine
      macrophages were incubated. No cellular uptake of the DP-LDL complex by
      macrophages was found until 6 h after the start of incubation, but this gradually
      increased from 12 to 48 h. On the other hand, the cellular uptake of the oxidized
      DP-LDL complex was already apparent at 3 h after the start incubation, and then
      markedly increased until 48 h incubation along with that of the lipid emulsion
      (LE) containing DP (DP-LE). The cellular uptake of DP-LE by foam cells was
      significantly lower than that by macrophages. However, the cellular uptake of DP
      LDL complex by foam cells was similar to that by macrophages. These findings
      suggest that the DP-LDL complex is oxidatively modified, and then incorporated
      into macrophages and foam cells through the scavenger receptor pathway. Since
      selective delivery of drugs into foam cells in the early stage of atherosclerosis
      is a useful protocol for antiatherosclerosis treatment, the DP-LDL complex
      appears to be a potentially useful drug-carrier complex for future
      antiatherosclerotic therapy.

PMID- 14577973
TI  - Single chain antibody vaccination in mice against human ovarian cancer enhanced
      by microspheres and cytokines.
AB  - Experimental studies using monoclonal antibody have demonstrated that anti
      idiotypic immunity can be enhanced by microspheres or cytokines. The underlying
      physiological principles behind these strategies involve sustained release of
      antigen and arousal of the immune system. In this study, a murine model was used
      to investigate the combination effect of microspheres and cytokines on anti
      idiotypic response. A single chain antibody scFv-pDL1.0, which recognizes the
      human ovarian cancer antigen CA125 was formulated in microspheres and injected to
      mice alone or in the presence of colony stimulating factor (GM-CSF) or tumor
      necrosis factor (TNF-alpha). The immunization of mice with formulated single
      chain antibody and cytokines resulted in enhanced production of anti-idiotypic
      antibody, and which subsequently induced the production of anti-anti-idiotypic
      antibody. These results raise the possibility of cancer immunotherapy by
      administration of single chain antibody encapsulated in microspheres with GM-CSF
      or TNF-alpha.

PMID- 14577974
TI  - In-vitro evaluation and vaginal absorption of metronidazole suppositories in
      rabbits.
AB  - Vaginal suppository formulations of metronidazole were prepared using six
      different bases as Witepsol H15, Cremao, Ovucire WL2944, Ovucire WL3264, PEG
      1500, PEG 6000. Three different dissolution methods were used to evaluate the in
      vitro drug release from the suppositories. The diffusion studies were performed
      through synthetic (cellophane) and natural membrane (rabbit vagina), but the drug
      did not show good permeation characteristics from natural membrane. Ovucire
      WL3264 suppositories of metronidazole labeled with 99mTc (Tecnetium-99m) were
      used for the vaginal absorption and biodistribution studies in the rabbits.
      Scintigraphic images were collected after vaginal administration of the labeled
      suppositories using SPECT gamma fitted with a low energy, high-resolution
      parallel hole collimator. The labeled drug showed high biodistribution in urine
      beside vaginal site. The results of this study suggested that the Ovucire WL3264
      suppository of metronidazole prepared for vaginal infections could also be
      effective in the urinary infections.

PMID- 14577976
TI  - C. Everett Koop, M.D., Sc.D.: a visionary leader of science-based public health
      policy and tobacco control.

PMID- 14577977
TI  - Tobacco addiction: accomplishments and challenges in science, health, and policy.

PMID- 14577978
TI  - Nicotine metabolite ratio as a predictor of cigarette consumption.
AB  - The rate of nicotine metabolism is hypothesized to be a determinant of how much a
      person smokes. That is, rapid metabolizers would be expected to need more
      nicotine and, therefore, smoke more than slow metabolizers. Nicotine is
      metabolized extensively by the liver enzyme CYP2A6, primarily to cotinine.
      Cotinine is itself metabolized by CYP2A6 to 3'-hydroxycotinine (3-HC). The ratio
      of metabolite to parent (i.e., 3-HC:cotinine) would be expected to reflect CYP2A6
      activity. We measured the ratio of 3-HC:cotinine in the urine of 72 smokers. This
      ratio was significantly correlated with the number of cigarettes smoked per day
      (r=.33, p=.005), though not with the Fagerstrom Test for Nicotine Dependence.
      This finding supports the hypothesis that the rate of nicotine metabolism is a
      determinant of the level of cigarette consumption and supports the use of the 3
      HC:cotinine ratio as a noninvasive marker of nicotine metabolism.

PMID- 14577979
TI  - A comparison of self-report measures of nicotine dependence among male
      drug/alcohol-dependent cigarette smokers.
AB  - This study examined the psychometric properties and validity of the Fagerstrom
      Tolerance Questionnaire (FTQ), the Fagerstrom Test for Nicotine Dependence
      (FTND), and the Heaviness of Smoking Index (HSI) when used as self-report
      measures of nicotine dependence among male drug/alcohol-dependent smokers (n=191
      participants in a large stop-smoking study). All three measures had fairly low
      internal consistency. The FTQ and FTND had similar two-factor structures, but the
      FTND factor structure accounted for a greater percentage of the item variance.
      All three measures were significantly correlated in the expected directions with
      several independent self-report and biochemical indicators of nicotine dependence
      (e.g., cigarette pack-years, cotinine) and with baseline measures of smoking
      topography. The FTND outperformed the FTQ on several correlations, and the HSI
      outperformed both the FTQ and the FTND. Results concerning correlations between
      each of the three measures and indicators of compensation in response to
      reductions in nicotine availability were equivocal. The HSI and FTND were
      predictive of at least 4 weeks of biochemically verified postquit abstinence
      among a subsample of individuals receiving smoking treatment (n=93). All three
      measures had mediocre psychometric properties, and the magnitudes of their
      relationships with independent indicators were generally modest. All three
      measures appeared to be valid as self-report measures of nicotine dependence
      among male drug/alcohol-dependent individuals. The HSI appeared to be the best of
      the three measures; thus, studies of drug/alcohol-dependent smokers should be
      sure to report the results from this measure. Efforts to develop self-report
      measures of nicotine dependence with better properties and performance in this
      population should continue to be pursued.

PMID- 14577980
TI  - Pharmacokinetics of a nicotine polacrilex lozenge.
AB  - To evaluate the pharmacokinetic characteristics of the 2-mg and 4-mg nicotine
      polacrilex lozenges, the following four separate studies were conducted in
      healthy adult smokers: (a) A single-dose, four-way crossover (replicate design)
      study to compare the 4-mg lozenge and the 4-mg nicotine polacrilex gum, (b) a
      single-dose, two-way crossover study to compare the 2-mg lozenge and the 2-mg
      gum, (c) a multiple-dose, four-way crossover study to compare the lozenges
      administered every 90 min and the gums administered every 60 min at 2- and 4-mg
      dose levels, and (d) a single-dose, three-way crossover study to compare the
      pharmacokinetic profiles of the 4-mg lozenge when administered in three different
      ways: (i) Used as directed, (ii) chewed and immediately swallowed, and (iii)
      chewed, retained in the mouth for 5 min, and then swallowed. The single-dose
      studies consistently demonstrated 8%-10% higher maximal plasma concentrations and
      25%-27% higher AUC values (area under the concentration-time curve) from the
      lozenges compared with the gums at the 2- and 4-mg dose levels, probably owing to
      the residual nicotine retained in the gum. The multiple-dose study applying
      different dosing intervals (i.e., every 90 min for the lozenges and every 60 min
      for the gums) resulted in approximately 30% lower AUC(0-t) values for the
      lozenges compared with those for the gums. Administration of the lozenge contrary
      to the label-specified instructions for use did not lead to a faster or higher
      absorption of nicotine. These pharmacokinetic characteristics should allow the
      lozenge to become an effective and safe therapeutic alternative for smoking
      cessation.

PMID- 14577981
TI  - Tobacco Craving Questionnaire: reliability and validity of a new multifactorial
      instrument.
AB  - This study documented the initial reliability and validity of the Tobacco Craving
      Questionnaire (TCQ), a new multidimensional questionnaire to assess tobacco
      craving. Current cigarette smokers (n=213) not attempting to reduce or quit
      smoking completed the 47-item TCQ and other forms assessing demographics, tobacco
      and other drug use history, quit attempts, and current mood. Exploratory factor
      analyses and structural equation modeling indicated that a four-factor solution
      best described the item structure. Factor subscales derived from the 17 items
      with significant loadings had low to high internal consistencies and interitem
      correlations and exhibited low to moderate, positive intercorrelations. Factor
      scales were significantly correlated with single-item measures of craving,
      current mood, and daily cigarette smoking. Results indicated that four specific
      constructs characterized craving for tobacco: (a) Emotionality, or smoking in
      anticipation of relief from withdrawal symptoms or negative mood, (b) expectancy,
      or anticipation of positive outcomes from smoking, (c) compulsivity, or an
      inability to control tobacco use, and (d) purposefulness, or intention and
      planning to smoke for positive outcomes. These preliminary data suggest that the
      TCQ is a reliable and valid instrument for assessing tobacco craving in
      individuals not attempting to reduce or quit smoking.

PMID- 14577982
TI  - A multidimensional model for characterizing tobacco dependence.
AB  - The standard tool for assessing tobacco dependence is the Fagerstrom Tolerance
      Questionnaire (FTQ) or its more recent variant, the Fagerstrom Test for Nicotine
      Dependence (FTND). Although both of these scales reportedly assess physiological
      dependence on nicotine, they might not tap some facets of dependence,
      particularly psychosocial factors. To determine whether tobacco dependence
      exhibits multidimensional properties, we examined two existing, independent data
      sets, one from SRI International (n=443) and another from the University of
      Michigan (n=445). Based on our knowledge from existing literature, standard
      psychometric statistical analyses, and results from exploratory factor analysis
      using SRI's data set, we identified two competing models for dependence
      representing a hybrid of the FTQ/FTND and the Smoking Motives Questionnaire. We
      then examined these models using confirmatory factor analysis with data from the
      University of Michigan. We characterized the final model by five first-order
      factors, each consisting of two to four items, and one higher-order factor. The
      first-order factors were termed stimulation, automaticity, sedation, psychosocial
      motives, and morning smoking; the higher-order factor, tobacco dependence,
      underlay each of the first-order factors. The ranges of interitem correlations
      and Cronbach's alpha estimates of internal consistency for the first-order
      factors were .34 - .68 and .64 - .81, respectively. Results of these analyses
      support the hypothesis that tobacco dependence is multidimensional.

PMID- 14577983
TI  - Switching to lower tar cigarettes does not increase or decrease the likelihood of
      future quit attempts or cessation.
AB  - This study examined whether switching to low-tar cigarettes predicts future quit
      attempts or smoking cessation. Prior studies of whether switching to low-tar
      cigarettes increases or decreases cessation behavior have produced contradictory
      results. We believed a large, prospective population-based study was needed.
      Participants in the Community Intervention Trial for Smoking Cessation (COMMIT),
      who were smokers in 1989 and 1991 and provided their smoking status in a 1993
      interview, provided product code information so that the tar categories of their
      cigarettes could be identified. Smokers' brands were classified as ultralight (0
      6 mg tar), light (7-15 mg tar), and regular (16+ mg tar). The main predictor
      measure was switching to a lower tar yield category: 8% of baseline light smokers
      and 19% of baseline regular smokers switched to a lower yield product between
      1989 and 1991. The main outcome measures were attempts to quit and successful 6
      month cessation. Despite greater desire to quit among switchers, switching down
      was not associated with increased or decreased number of attempts to quit or the
      likelihood of future cessation. No evidence of differential effects was found for
      subgroups of smokers, including those who did and did not believe that low-tar
      cigarettes are safer. The data show that switching to a low-tar cigarette does
      not appear to increase or decrease the likelihood of future cessation, though
      motivation to stop smoking may be associated with switching.

PMID- 14577984
TI  - Smoking topography: reliability and validity in dependent smokers.
AB  - Data from two studies were analyzed to determine whether smoking through the
      mouthpiece of a topography unit yields consistent measures over time and to
      verify that smoking through a mouthpiece results in a similar degree of smoke
      exposure as conventional smoking. In both studies, subjects smoked their usual
      brand of cigarette ad libitum. In study A, subjects (n=7) smoked through a
      mouthpiece on 4 separate experimental days. In study B, subjects (n=10) smoked on
      2 separate days: Once conventionally and once through a mouthpiece. In both
      studies, exhaled carbon monoxide (CO) and physiological effects (heart rate and
      blood pressure) were measured before and after smoking. In study B, plasma
      nicotine concentrations also were measured. In study A, puff volume, puff
      duration, interpuff interval, and maximum puff velocity averaged 30.8 ml,.9 s,
      19.9 s, and 44.6 ml/s, respectively. Intraclass correlation coefficients computed
      for puff volume (0.66), puff duration (0.75), and maximum puff velocity (0.68)
      indicated that these measures showed good reliability. In study B, smoking
      through the mouthpiece yielded similar topographical (time to smoke and number of
      puffs per cigarette) measures as conventional smoking. Also similar were changes
      in biochemical values: Plasma nicotine (18.5 ng/ml vs. 25.5 ng/ml), exhaled CO
      (4.6 ppm vs. 5.1 ppm), and heart rate (8.6 beats/min vs. 7.4 beats/min) for
      conventional and topography mouthpiece smoking conditions, respectively.
      Topography measures did not differ significantly between the two studies.
      Overall, the data from these two small-sample studies suggest that smoking
      topography provides a valid and reliable index of conventional smoking and an
      indirect measure of smoke exposure.

PMID- 14577985
TI  - The representation of smoking expectancies by single-word adjectives and their
      relationship to smoking characteristics.
AB  - A pool of single-word adjectives representing smoking outcome expectancies was
      derived and tested in two studies. In Study One, smoking-related words were
      generated and then clustered together to form 39 categories representing smoking
      expectancy nodes. Analysis of the number of times words in each category were
      generated indicated that expectancies varied as a function of smoking status
      (measured at two levels: Ever smoked daily vs. never smoked daily), smoking
      history (current vs. past smoker), and dependence (nondependent vs. dependent).
      In Study Two, participants rated the words in terms of expectations of smoking
      outcomes. A principal components analysis of the ratings indicated that three
      components accounted for 74.10% of the variance in participants' ratings:
      Component 1 (adverse effects), 30.92%; component 2 (positive image), 28.08%; and
      component 3 (positive mood), 15.09%. Further analyses revealed that ratings of
      words comprising the three components differed as a function of smoking status
      (measured at three levels: Never smoked daily, daily nondependent smoker, daily
      dependent smoker), with dependent smokers rating the outcomes associated with all
      three components as occurring more frequently when they smoked compared with
      nondependent smokers or those who never smoked daily. The results suggest that
      the single-word adjectives are appropriate for use in research investigating
      smoking outcome expectancies.

PMID- 14577986
TI  - Placebo effects of tobacco smoking and other nicotine intake.
AB  - Nicotine intake is a necessary but insufficient factor in maintaining tobacco
      smoking behavior, and nonpharmacological factors associated with smoking play a
      key role. Some of these factors may influence smoking behavior by eliciting
      placebo effects, or responses related specifically to the belief that one is
      consuming a drug. Greater knowledge of placebo effects of smoking would improve
      our understanding of factors that maintain smoking behavior, thereby aiding
      efforts to develop treatments to counter the influence of these factors. In
      addition, better understanding of placebo effects from other means of nicotine
      intake could help determine mechanisms of the therapeutic actions of nicotine
      replacement therapy, perhaps enhancing its efficacy in smoking cessation. Placebo
      effects of smoking or other nicotine intake have received little research
      attention. In this review, we first discuss common terms and methods of placebo
      research, especially the balanced-placebo design. We then examine the limited
      research directly assessing placebo effects of smoking and other nicotine intake,
      namely studies that manipulated instructions to subjects about the drug content
      of an ingested substance. Finally, we examine other studies relevant to gauging
      the likely magnitude of placebo smoking effects. In an effort to encourage more
      research on these placebo effects, we pay substantial attention to future
      directions. Among recommendations are testing the utility of the balanced-placebo
      design and other rigorously controlled designs, and including multiple measures
      of placebo effects in addition to self-report. Future research also should
      explore the moderating influences of the environmental context and of individual
      difference factors on placebo effects of smoking and other nicotine intake.

PMID- 14577987
TI  - Development and validation of a self-rating scale for positive- and negative
      reinforcement smoking: The Michigan Nicotine Reinforcement Questionnaire.
AB  - Positive- and negative-reinforcement consequences of smoking were assessed using
      a self-report inventory. Data from 429 current smokers (348 women, 81 men) were
      subjected to an exploratory factor analysis, with concurrent validation of
      resulting scales in 288 current smokers (235 women, 53 men), controlling for sex
      and age. The solution with three factors--positive reinforcement, negative
      reinforcement, and smoking patterns--provided the clearest and most interpretable
      factor solution. The Michigan Nicotine Reinforcement Questionnaire (M-NRQ), which
      yields positive- and negative-reinforcement scales, was developed based on these
      results. Positive-reinforcement smoking was associated with higher scores on
      novelty seeking, reward dependence, alcohol dependence, and pleasurable
      sensations upon early smoking experimentation, and with lower scores on
      displeasurable sensations and nausea upon early smoking experimentation. Negative
      reinforcement smoking was associated with higher scores for nicotine dependence,
      depression, anxiety, and harm avoidance. The M-NRQ has potential as a diagnostic
      tool for individualizing behavioral intervention and pharmacotherapy and also may
      be useful in identifying new phenotypes for genetic research on smoking.

PMID- 14577988
TI  - Electronic monitoring of long-term use of the nicotine nasal spray and predictors
      of success in a smoking cessation program.
AB  - This study evaluated the efficacy of prolonged administration (18 months) of a
      nicotine nasal spray in smoking cessation and attempted to characterize the
      pattern of use of the nasal spray with a specially developed electronic monitor
      in an effort to assess the factors associated with cessation success or failure.
      Study participants were 92 patients in a smoking cessation unit of a medical
      outpatient clinic in Switzerland. Participants were daily smokers who had smoked
      for more than 5 years and were highly motivated to quit. The main outcome measure
      was the number of abstainers at 12 and 24 months. Their use of the spray was
      monitored using a microchip (MDILog) that recorded the date and time of every
      actuation. Success rates were 17.4% at 12 months and 9.8% at 24 months. During
      the first month of study, median use was 12 puffs/day in abstainers and 6
      puffs/day in failures (p=.049). Abstainers used the spray less in the morning
      compared with failures (26.6% vs. 32.8% of the total median daily dose; p=.028).
      By contrast, abstainers used the spray more in the evening/night compared with
      failures (35.3% vs. 26.7% of the total median daily dose; p=.007). Abstinence
      during the first two weeks was associated significantly with cessation success at
      6 months (OR=17.10) and 24 months (OR=11.09). Although the pattern of use of the
      nasal spray differed between successful quitters and failures (used in higher
      doses by the successful quitters), mean daily consumption during the first month
      was not predictive of success. Mean daily consumption of the nicotine nasal spray
      remained lower than expected in most participants, particularly in failures.

PMID- 14577989
TI  - Assessment of the relative reinforcement value of smoking and drinking using a
      multiple-choice measurement strategy.
AB  - To examine the relative reinforcement value of smoking and drinking, separately
      and in combination, a multiple-choice questionnaire was administered to 78
      individuals seeking outpatient treatment for concurrent tobacco and alcohol
      dependence. Participants made choices between pairs of substances and then
      between each substance and a series of monetary values. Results demonstrated that
      the combination (one cigarette and one drink) was preferred over each individual
      substance. The mean crossover monetary points for a cigarette (8.1 US dollars)
      and a drink (10.8 US dollars) were significantly lower than for the combination
      (13.75 US dollars). Correlational analyses revealed positive associations between
      drug reinforcement values and dependence-related measures. The utility of this
      measurement strategy in understanding and treating polydrug use is discussed.

PMID- 14577990
TI  - Nicotine dependence measures among adolescents with psychiatric disorders:
      evaluating symptom expression as a function of dependence severity.
AB  - Using methods based in item response theory, we examined a structured interview
      assessment of Diagnostic and Statistical Manual of Mental Disorders, 4th edition
      (DSM-IV) nicotine dependence and the Modified Fagerstrom Tolerance Questionnaire
      (mFTQ) symptoms to explore the expression of particular symptoms as a function of
      level of nicotine involvement in a sample of 191 adolescents with psychiatric
      disorders. Despite our attempts to capture a broad range of smokers, 64% of teens
      were daily smokers and 68% met DSM-IV criteria for nicotine dependence. This
      paper describes the relative severity of DSM-IV and mFTQ items, as well as each
      item's ability to discriminate among individuals at various levels of nicotine
      involvement. Comparisons across measures revealed that the mFTQ was not
      particularly sensitive to individual variation in DSM-IV symptom counts,
      suggesting the physiological components were not strongly related to the
      predominantly cognitive and behavioral components of the DSM-IV nicotine
      dependence syndrome. However, the mFTQ relative to the DSM-IV consistently showed
      stronger relationships to the immediate consequences of nicotine deprivation
      (urge, craving), supporting the conceptualization of the mFTQ as measuring
      nicotine exposure. These analyses provide us with some preliminary understanding
      of the severity of particular symptoms and the order in which symptoms are likely
      to be expressed across levels of nicotine dependence.

PMID- 14577991
TI  - Determination of tar, nicotine, and carbon monoxide yields in the smoke of bidi
      cigarettes.
AB  - A survey of the nicotine, tar, and carbon monoxide (CO) levels in mainstream
      smoke from 21 brands of bidi cigarettes and five brands of traditional cigarettes
      was conducted using a variation of the Federal Trade Commission (FTC)
      standardized cigarette smoking machine method. The primary difference between
      this method and the FTC method was a reduction of the 60-s puff interval to 15 s.
      The shorter puff interval was required to prevent the bidi cigarettes from self
      extinguishing and may represent a closer approximation to human usage. The goal
      of this study was to evaluate the smoke-delivery potential for tar, nicotine, and
      CO in mainstream smoke from bidi cigarettes compared with traditional domestic
      cigarettes smoked under identical conditions. Approximately half of the bidi
      brands examined were marketed as filtered varieties. Unlike traditional
      cigarettes, the filtered and unfiltered bidi brands yielded comparable smoke
      deliveries. Thus, a filtered bidi cigarette brand does not provide any harm
      reduction benefit that might result from a reduction in levels of tar, nicotine,
      and CO compared with an unfiltered variety. Our findings indicate that bidi
      cigarettes can deliver high levels of tar (77.9+/-9.5 mg/bidi), nicotine (2.7+/
      .4 mg/bidi), and CO (39.2+/-5.7 mg/bidi). In comparison, traditional cigarettes
      smoked using the bidi cigarette protocol have lower tar and CO yields, but have
      nicotine deliveries comparable with bidi cigarettes.

PMID- 14577992
TI  - Nondaily smokers: a descriptive analysis.
AB  - To describe the characteristics of persons in the United States who smoke but do
      not smoke daily, we analyzed 1997-1998 data from the National Health Interview
      Survey (NHIS). The NHIS collects self-reported information on cigarette smoking
      from a representative sample of the U.S. civilian, noninstitutionalized
      population aged 18 years or older through in-home surveys. Nondaily smokers were
      defined as persons who had ever smoked 100 cigarettes, smoked "some days," and
      smoked on fewer than 30 of the past 30 days. In 1997-1998, an estimated 16.0% of
      current smokers were nondaily smokers. Being a nondaily smoker was more common
      among smokers aged 18-24 years (19.9%) than among those aged 45-64 years (12.0%),
      more common among Black and Hispanic smokers (19.2% and 29.9%, respectively) than
      among White smokers (13.9%), and more common among smokers with at least a
      college education (28.2%) than among those with 9-11, 12, or 13-15 years of
      education (10.0%, 12.5%, or 15.9%, respectively). Mean cigarettes smoked per day
      for those who had smoked on 1-9, 10-19, and 20-29 of the past 30 days equaled
      3.9, 5.3, and 7.0, respectively, compared with 19.0 for daily smokers. Nondaily
      smokers were more likely than daily smokers to have a quit attempt in the past
      year (55.2% vs. 40.0%). In conclusion, rates of nondaily smoking vary
      substantially by age, race/ethnicity, and educational attainment. Differences by
      education suggest that this behavior may be influenced by knowledge and social
      norms. Nondaily smoking may be a useful intermediate outcome for assessing
      changes in smoking prevalence. Cessation interventions need to be tailored for
      nondaily smokers, who may differ from daily smokers in important ways.

PMID- 14577993
TI  - Recent advances in nicotine and tobacco research. Ninth SRNT annual meeting. New
      Orleans, Louisiana, USA. 19-22 February 2003.
AB  - The ninth annual meeting of the Society for Research on Nicotine and Tobacco
      (SRNT) was held February 19-22, 2003, in New Orleans, Louisiana. With over 800
      registered attendees, this year's meeting was the largest to date. The 3-day
      scientific program included C. Everett Koop as the keynote speaker, four
      exemplary plenary speakers, 10 symposia, nine oral paper sessions, and four
      poster sessions that contained nearly 100 presentations per session. The meeting
      content emphasized three major areas of SRNT's scientific focus:
      Epidemiology/public health research, preclinical research, and clinical research.
      Thus, the meeting was an outstanding opportunity to interact with and learn from
      colleagues engaged in the broad area of nicotine and tobacco research around the
      globe. Additional events included pre- and postconference meetings, evening
      workshops that ranged from future directions for global tobacco research to grant
      writing for the new investigator, several scientific and travel awards, a
      members' meeting, and an opening reception. The scientific excellence and
      innovation presented at this year's meeting signifies SRNT's continued
      contributions to advancing our understanding of nicotine addiction and tobacco
      use.

PMID- 14577994
TI  - Access to diabetes services: the experiences of Bangladeshi people in Bradford,
      UK.
AB  - Recent years have seen a renewed emphasis in UK healthcare policy on access to
      services, yet there has been little research into possible inequalities in access
      for people from different ethnic backgrounds. This paper examines access from the
      point of view of a group of Bangladeshi people with diabetes, whose views were
      obtained as part of a wider evaluation of diabetes services. Their message is a
      powerful one. The problems they experienced, however, cannot be attributed solely
      to cultural insensitivity, in which providers adopt a 'like it or lump it'
      approach. The wider evaluation provides a context within which to identify
      similarities with, as well as differences from, other groups in the community,
      and the findings show that the experiences of this vulnerable group highlight
      more general weaknesses in service provision. The paper also shows that
      conventional analysis of access in terms of barriers to be overcome misses a
      crucial dimension: the ability to make full use of services. Gaining access does
      not mean that needs will be met appropriately, and patients vary in the extent to
      which they are able and enabled to play an active role in obtaining the services
      they need.

PMID- 14577995
TI  - Cross-cultural experiences of maternal depression: associations and contributing
      factors for Vietnamese, Turkish and Filipino immigrant women in Victoria,
      Australia.
AB  - OBJECTIVES: To investigate in an Australian study of immigrant women conducted 6
      9 months following childbirth (a) the associations of a range of demographic,
      obstetric, health and social context variables with maternal depression, and (b)
      women's views of contributing factors in their experiences of depression. DESIGN:
      Three hundred and eighteen Vietnamese, Turkish and Filipino women participated in
      personal interviews conducted by three bicultural interviewers in the language of
      the women's choice. Utilising three approaches to the assessment of maternal
      depression, the consistency of associations on the different measures is
      examined. Women's views of contributing factors are compared with previous
      research with largely English-speaking Australian-born women. RESULTS: Analysis
      of the associations of maternal depression revealed considerable consistency in
      associations among the three approaches to assessing depression. Significant
      associations with depression on at least two of the measures were seen for:
      mothers under 25 years, shorter residence in Australia, speaking little or no
      English, migrating for marriage, having no relatives in Melbourne, or no friends
      to confide in, physical health problems, or a baby with feeding problems. There
      were no consistent associations found with family income or maternal education,
      method of delivery and a range of other birth events, or women's views about
      maternity care. The issues most commonly identified by women in this study as
      contributing to depression are similar to those found previously for Australian
      born women: isolation (in this study, including being homesick)--29%; lack of
      support and marital issues--25%; physical ill-health and exhaustion--23%; family
      problems--19%, and baby-related issues--17%. There were some differences in the
      importance of these among the three country-of-birth groups, but all except
      family issues were in the top four contributing factors mentioned by women in all
      groups. CONCLUSIONS: These findings support the evidence for quite marked cross
      cultural similarity in the associations of maternal depression and in women's
      views about their experiences.

PMID- 14577996
TI  - The experiences of postnatal depression in women from black and minority ethnic
      communities in Wiltshire, UK.
AB  - OBJECTIVES: To describe the experiences of women suffering from postnatal
      depression in black and minority ethnic communities in Wiltshire, UK. DESIGN:
      Semi-structured interviews and focus groups with women across Wiltshire with
      current and past experience of postnatal depression. EPDS data are also reported.
      Qualitative data (via telephone and face-to-face interviews) were also collected
      from GPs and health visitors who worked with these women. RESULTS: Qualitative
      analysis identified four main themes that were part of the experience of
      postnatal depression for the women and the primary health care professionals in
      contact with them--issues specific to pregnancy and birth (including postnatal
      depression), issues specific to primary health care, issues relating to culture,
      and 'other' issues. This latter theme describes the multitude of problems that
      many of the women endured, e.g. family/marital problems, violence, drinking
      alcohol, bereavement, financial difficulties, unemployment, accommodation and
      (racial) harassment. CONCLUSIONS: All the women had problematic lives, affected
      by a multitude of factors, and raised a number of serious concerns that related
      to health and social care. This has implications for practice and service
      provision, as demonstrated by the data from GPs and health visitors, in, for
      example, the provision of advice and information (and in different languages),
      training, improved communication and inter-agency working, in this area (where
      the research was conducted) and elsewhere in England. More research is needed to
      further explore the needs of women from minority ethnic groups, taking issues of,
      for example, cultural specificity and urbanity/rurality into account. Further
      research also needs to investigate ways of offering help and support to this
      patient group.

PMID- 14577997
TI  - Roma health issues: a review of the literature and discussion.
AB  - OBJECTIVES: Roma health issues are under-studied from a comprehensive,
      epidemiological perspective. The Roma peoples (including 'Travellers') have been
      living in and around Central and Eastern Europe for centuries, and may be one of
      the oldest systematically oppressed minority groups in Europe. This review
      examines the research literature in regard to the health and epidemiology of this
      group with the aim of examining the breadth and depth of the literature and
      reflecting on the primary and applied research needed to address the health needs
      of Roma groups. DESIGN: Internet, database and ancestral searches were conducted
      via such electronic databases as Medline and PubMed. Ancestral searches involved
      consulting previous literature reviews in select topical areas and obtaining all
      appropriate, primary literature. The time parameters of the search began with the
      year 1990 to current but was later expanded to 1985-2003 in order to capture
      slightly older published work. RESULTS: This paper describes what is known
      concerning Roma health via a review of the published studies, with special
      emphasis on population health and epidemiological studies. One hundred and twenty
      nine articles are reviewed and discussed. The majority of research (50%) examines
      the genetic characteristics of this group. CONCLUSIONS: Surveillance and
      population health indices for this international minority population is scarce to
      lacking in the published literature. Concluding comments focus on the unique
      character of the study population and the need for scientific studies of Roma
      health issues and the cultural concerns which might affect them.

PMID- 14577998
TI  - Cervical cancer screening in a Vietnamese nominal cohort.
AB  - BACKGROUND: In New South Wales (NSW) information on migrant status is not
      collected in routinely recorded cervical screening data, yet some migrant groups,
      particularly Vietnamese-born women, have a higher incidence of cervical cancer
      and, purportedly, lower cervical screening rates than Australian-born women. To
      investigate this, screening rates in a cohort of women with Vietnamese surnames
      were estimated and compared with survey data. METHODS: A cohort of women with
      common Vietnamese surnames was extracted from the NSW electoral roll and matched
      over three periods with data held on the NSW Pap Test Register (PTR), and
      estimates of cervical screening in the cohort derived. Screening rates for each
      of the three periods were pro-rated to biennial rates, and time-related changes
      compared. Screening rates in the cohort were also compared to those in Vietnamese
      migrant respondents to a population-based health interview survey. RESULTS:
      Estimated biennial screening rates in the overall Vietnamese nominal cohort of
      women aged 20-69 years were significantly and substantially lower than those for
      NSW overall, by 10-12 percentage points. Screening rates in the Vietnamese cohort
      were found to increase over the study period, from 44% for 1997/98 to 47% for
      1998/99. While the biennial screening rate for 1998 in the nominal cohort was 19
      percentage points lower than the self-reported surveyed screening rate of 63%,
      the relative screening ratios between Vietnamese and all NSW women were similar
      for both data sources. CONCLUSION: This study demonstrates the feasibility of
      estimating and monitoring cervical screening participation in minority groups
      with distinctive names using a Pap Test Register and information from a
      population register.

PMID- 14577999
TI  - Social networks and coronary heart disease risk factors in South Asians and
      Europeans in the UK.
AB  - OBJECTIVES: To compare the social networks of South Asian (Indians, Pakistanis
      and Bangladeshis) and European-origin participants in the Newcastle Heart
      Project, and to examine the relationships between social network sizes and
      coronary heart disease (CHD) risk factors in both groups, testing the hypothesis
      that part of the reason for high rates of CHD in the South Asian UK population
      may be social isolation. DESIGN: Participants were 684 South Asian (259 Indians,
      305 Pakistanis, 120 Bangladeshis) and 825 European men and women aged 25-74
      years, who completed a questionnaire and were screened for CHD risk factors in a
      cross-sectional study. RESULTS: South Asians were more likely to be married than
      Europeans, had bigger households and were more likely to attend a place of
      worship regularly. Europeans saw more friends and relatives on a regular basis
      than did South Asians. There was also some heterogeneity between the South Asian
      groups. Europeans who reported bigger social networks were less likely to smoke
      than those with smaller networks, but there was little evidence of an association
      between social network size and waist circumference, blood pressure or TC:HDL
      ratio in either Europeans or South Asians. CONCLUSION: The results provided only
      partial support for the hypothesis that South Asians in the UK are socially
      isolated, and suggest that South Asians and Europeans in the UK utilise different
      sources of social support. Future work should acknowledge variation in sources of
      social support between ethnic groups, and should explore the possibility that
      different mechanisms link social support and health in different ethnic groups.

PMID- 14578000
TI  - Meeting the mental health needs of older adults with intellectual disabilities.

PMID- 14578001
TI  - Responding to the challenges of ageing and dementia in intellectual disability in
      Ireland.
AB  - The intellectual disability (ID) population in Ireland is ageing and the number
      of older persons with the dual disability of ID and dementia is increasing. In
      spite of these demographic trends, as in other countries adequate policy and
      service provision for this population are lacking. This paper draws upon data
      available on the population with ID and dementia, reviews both generic and ID
      specific literature, considers the policy context and argues for a specific model
      of service provision. A service model is proposed for the development of
      multidisciplinary specialist teams within ID, delivered through mobile regional
      ID dementia clinics.

PMID- 14578002
TI  - A memory clinic for older people with intellectual disabilities.
AB  - Cognitive decline in older people with intellectual disabilities (ID) is often
      under-recognized. Following the publication of the National Service Framework for
      Older People and the white paper Valuing People, older people with intellectual
      disabilities of all aetiologies should have access to a systematic assessment of
      their cognitive function in order to detect decline in cognition and adaptive
      skills and implement appropriate treatments as early as possible. The development
      of a memory clinic for older people with ID is described, including instruments
      used and characteristics of attendees. Such projects are in line with current UK
      government policies and can contribute to the improvement of standards of care
      and support research in this vulnerable group of people.

PMID- 14578003
TI  - Associations between behavior disorders and health status among older adults with
      intellectual disability.
AB  - Few studies have examined the relationship of behavior and health status among
      aging persons with intellectual and developmental disabilities (I/DD). Behavioral
      disorders, which often are coincident with functional decline in older persons
      with I/DD, may be more related to medical morbidity than previously reported.
      This cross-sectional study examined the association between health status and
      behavior disorders with increasing age in a cohort of 60,752 adults with I/DD
      clustered into four adult-age groupings (21-44, 45-59, 60-74, and >74). Age
      grouping data suggested an association between morbidity and increased likelihood
      of behavior symptoms in all but the oldest age grouping. The magnitude of the
      association and trend varied by specific disease across age groupings compared to
      that found in healthy cohorts. About 25% of the adults with I/DD had psychiatric
      diagnoses and the frequency of such diagnoses did not decrease with age grouping.
      These results suggest that adverse health status may increase the likelihood of
      persistent behavioral disturbances in older persons with I/DD. Moreover,
      behavioral disorders may be sentinels for occult medical morbidity, which in turn
      may be responsive to intervention.

PMID- 14578004
TI  - Diagnostic instruments for dementia in older people with intellectual disability
      in clinical practice.
AB  - There is a need for simple and reliable screening instruments for dementia in the
      intellectual disability (ID) population that can also be used to follow their
      progress, particularly if they are being treated with anti-dementia drugs.
      Commonly used tests for the general population such as the Mini Mental State
      Examination (MMSE) are not appropriate for many people with ID. This paper is a
      literature review of alternative instruments that have been used in research or
      recommended by experts since 1991 and have the potential to be used as screening
      instruments. Two types of tests have been identified: those administered to
      informants, and those that rely on direct assessment of the individual. The most
      promising informant rated screening tool in most adults with ID including Down
      syndrome (DS) diagnosis is the Dementia Questionnaire for Persons with Mental
      Retardation (DMR). However, sensitivity in single assessments is variable and cut
      off scores need further optimisation. In those with DS, the Dementia Scale for
      Down Syndrome (DSDS) has good specificity but mediocre sensitivity. The Test for
      Severe Impairment and Severe Impairment Battery are two direct assessment tools
      that show promise as screening instruments, but need further evaluation.

PMID- 14578005
TI  - Humor coping, health status, and life satisfaction among older adults residing in
      assisted living facilities.
AB  - The present study examined the relationships between humor coping, health status,
      and life satisfaction among older residents of assisted living facilities. A
      structural equation model with latent variables was specified for the three
      variables. Health status was expected to directly affect humor coping and life
      satisfaction. Humor coping was hypothesized to have a direct association with
      life satisfaction and indirectly affect the relationship between health status
      and life satisfaction. Participants completed the Multidimensional Functional
      Assessment Questionnaire, Coping Humor Scale, and Life Satisfaction Index A. The
      relationships between health status and humor coping and health status and life
      satisfaction were statistically significant. Both the direct association of humor
      coping on life satisfaction and the intervening role between health status and
      life satisfaction were not supported. Humor as a coping strategy seems to be
      available to older adults who are in better health.

PMID- 14578006
TI  - Identification of psychological morbidity in older people in primary care by
      practice nurses.
AB  - Older people with psychological morbidity generally first present to health
      services in primary care, where they are increasingly seen by primary care
      nurses. In order to evaluate primary care nurses' identification of psychological
      morbidity, 190 older patients attending eight practice nurses completed the
      General Health Questionnaire (GHQ) and the practice nurses made an assessment as
      to the presence or absence of psychological problems. The practice nurses
      identified only 26% of probable cases of psychological morbidity identified by
      the GHQ. Their threshold for identification was high, rating only 12% of patients
      as experiencing psychological problems compared to 29% probable cases identified
      by the GHQ, and their accuracy was low (kappa for agreement between GHQ and nurse
      ratings = 0.23). Likelihood of identification depended on length and type of
      visit. The findings suggest that it may be unrealistic to expect practice nurses,
      without additional training and reorganisation of their work, to identify more
      than a minority of older patients with psychological morbidity in the course of
      their routine work.

PMID- 14578007
TI  - Group psychotherapy and people with dementia.
AB  - Psychotherapy and counselling approaches are being used increasingly with people
      with dementia, but there has been little structured research into the
      effectiveness of such work. This research reports findings from the evaluation of
      six, ten-week long psychotherapy groups for people with dementia in the south of
      England. Measures of depression and anxiety were taken independently of the
      clinical work at four time points: six weeks before the group began, at the start
      of the group, at the end of the group and at follow-up after a gap of ten-weeks.
      Forty-two participants entered the project at different points, of whom 19
      completed the baseline, intervention and follow-up phases of the project.
      Analysis of the data for depression and anxiety levels using a repeated measures
      ANOVA showed a statistically significant treatment effect for Cornell depression
      scores which was maintained at follow-up and a similar reduction in anxiety as
      measured by the rating for anxiety in dementia (RAID) which was borderline for
      significance. Although not all people with dementia would be suitable for group
      psychotherapy, nevertheless this research provides some of the first clear
      evidence that group psychotherapy may have a role to play in reducing levels of
      depression and anxiety of people with mild and moderate levels of dementia.

PMID- 14578008
TI  - Comparison of methods for analyzing longitudinal binary outcomes: cognitive
      status as an example.
AB  - Longitudinal data generate correlated observations. Ignoring correlation can lead
      to incorrect estimation of standard errors, resulting in incorrect inferences of
      parameters. In the example used here, standard logistic regression, a population
      averaged (PA) model fit using generalized estimating equations (GEE), and random
      intercept models are used to model binary outcomes at baseline, three and six
      years later. The outcomes indicate cognitive impairment versus no cognitive
      impairment in a sample of community dwelling elders. The models include both time
      invariant (age, gender) and time-varying (time, interactions with time)
      covariates. The absolute estimates from random-intercept models are larger than
      those of both standard logistic and GEE models. Compared to the model fit using
      GEE that accounts for time dependency, standard logistic regression models
      overestimate standard errors of time-varying covariates (such as time, and time
      by problems with activities of daily living), and underestimate the standard
      errors of time-invariant covariates (such as age and gender). The standard errors
      from the random-intercept model are larger than those from logistic regression
      and GEE models. The choice of models, GEE or random-intercept, depends on the
      research question and the nature of the covariates. Population-averaged methods
      are appropriate when between-subjects effects are of interest, and random-effects
      are useful when subject-specific effects are important.

PMID- 14578009
TI  - Linking depressive symptoms and functional disability in late life.
AB  - We hypothesized that the relationship of depressive symptoms to functional
      disability might be mediated by cognitive processes such as memory and problem
      solving. The study sample consisted of 147 community-dwelling older adults (mean
      age = 74.0 years, SD = 5.9). In regression models that included terms for age,
      gender, and years of education, depressive symptoms were significantly inversely
      associated with two performance-based measures of functioning: everyday problems
      test (beta = -0.15, p = 0.04) and observed tasks of daily living (beta = -0.14, p
      = 0.02). When memory and problem-solving ability were added to the model, the
      relationship of depressive symptoms with function was attenuated. A structural
      equation model based on our conceptual framework revealed that both memory and
      problem-solving abilities were important mediators in the relationship of
      depressive symptoms and functional disability. The results suggest that
      intervention studies intended to limit functional disability secondary to
      depression among older adults may need to consider the effect of depression on
      cognition.

PMID- 14578010
TI  - The pharmacology of psilocybin.
AB  - Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) is the major psychoactive
      alkaloid of some species of mushrooms distributed worldwide. These mushrooms
      represent a growing problem regarding hallucinogenic drug abuse. Despite its
      experimental medical use in the 1960s, only very few pharmacological data about
      psilocybin were known until recently. Because of its still growing capacity for
      abuse and the widely dispersed data this review presents all the available
      pharmacological data about psilocybin.

PMID- 14578011
TI  - Human alcoholism studies of genes identified through mouse quantitative trait
      locus analysis.
AB  - Coding region DNA sequence variants have been recently identified in several QTL
      candidate genes in a mouse model of differential sensitivity to alcohol [inbred
      long-sleep (ILS) and inbred short-sleep (ISS)]. This work has been extended into
      a human population characterized for their initial level of response to alcohol
      (LR). The coding region of one of the most promising of these candidate genes,
      zinc finger 133 (Znf133), has been sequenced completely in 50 individuals who
      participated in alcohol challenges at approximately age 20 and have been followed
      subsequently for the last 15 years. PCR products were obtained for the protein
      coding region of ZNF133 using human genomic DNA and directly sequenced using
      automated sequencers. Novel single nucleotide polymorphisms (SNPs) were detected
      by analyzing the sequence data using a suite of bioinformatics programs including
      Consed, Phred, Phrap and Polyphred. Five human SNPs were detected, two that
      correspond to amino acid changes in the protein, two that are silent DNA changes
      and one located in an intron. In this small sample, no significant association
      between any of the SNPs and alcohol diagnosis was detected. A follow-up of these
      SNPs in a larger sample should allow a more definitive conclusion to be reached.
      Significantly, the data presented here demonstrate the feasibility of directly
      testing genes in human alcoholic populations that had been identified first by
      comparative DNA sequencing of candidate genes located within mouse alcohol
      related QTLs, even without detailed knowledge of the gene's function.

PMID- 14578012
TI  - Similar rewarding effects of testosterone in mice rated as short and long attack
      latency individuals.
AB  - An attempt was made to confirm and extend the findings of an earlier study on the
      rewarding properties of testosterone in male mice using conditioned place
      preference (CPP). Previous results had only partially demonstrated such an effect
      because the reinforcement depended on environmental cues such as the colour of
      the compartment. High individual variability was evident, suggesting that basal
      levels of aggressiveness may modulate such effects. Animals were pre-screened for
      aggressive behaviour and allocated to short and long attack latency (SAL and LAL)
      categories. Five days later the CPP procedure started. This involved pre
      conditioning tests, conditioning and post-conditioning tests. SAL and LAL animals
      were treated with vehicle, 1 or 2 mg/kg of testosterone. During conditioning (on
      alternate days), a distinctive floor was paired four times with testosterone. On
      the intervening days animals were paired with a different floor with vehicle. CPP
      was clearly observed after testosterone treatment when the colour of the
      compartment was controlled in both SAL and LAL animals. These results provide
      additional support for the idea that testosterone and its derivatives have
      rewarding properties, which could explain processes of dependence.

PMID- 14578013
TI  - Correlations between orbitofrontal dysfunction and tobacco smoking.
AB  - Orbitofrontal cortex is involved in various reward and reinforcement processes in
      the human brain. There is both anatomical and functional evidence for a
      dysfunction of orbitofrontal cortex in substance abusers, and nicotine has been
      shown to activate reward-related structures in the brain similarly to other
      abused drugs. This study shows positive correlations between smoking parameters
      (smoking status and packs smoked per day) and impairment on putative measures of
      orbitofrontal dysfunction (go/no-go, antisaccades, delayed alternation and
      impulsivity ratings). While causality could not be determined, other research
      suggests that an orbitofrontal dysfunction predisposes one toward tobacco abuse.

PMID- 14578014
TI  - Intravenous flumazenil versus oxazepam tapering in the treatment of
      benzodiazepine withdrawal: a randomized, placebo-controlled study.
AB  - Flumazenil (FLU), a benzodiazepine (BZD) partial agonist with a weak intrinsic
      activity, was previously found unable to precipitate withdrawal in tolerant
      subjects submitted to long-lasting BZD treatment. The potential use of FLU to
      treat BZD withdrawal symptoms has also been evaluated tentatively in clinical
      studies. In the present experiment, FLU (treatment A) was compared with oxazepam
      tapering (treatment B) and placebo (treatment C) in the control of BZD withdrawal
      symptoms in three groups of BZD dependent patients. Group A patients (20)
      received FLU 1 mg twice a day for 8 days, and oxazepam 30 mg in two divided doses
      (15 mg + 15 mg) during the first night, oxazepam 15 mg during the second night
      and oxazepam 7.5 mg during the third night. FLU was injected i.v. in saline for 4
      hours in the morning and 4 hours in the afternoon, in association with placebo
      tablets. Group B patients (20) were treated by tapering of oxazepam dosage (from
      120 mg) and with saline solution (as placebo) instead of FLU for 8 days. Group C
      patients (10) received saline instead of FLU and placebo tablets instead of
      oxazepam for 8 days. FLU immediately reversed BZD effects on balance task and
      significantly reduced withdrawal symptoms in comparison with oxazepam and placebo
      on both self-reported and observer-rated withdrawal scales. The partial agonist
      also reduced craving scores during the detoxification procedure. In addition,
      during oxazepam tapering, group B patients experienced paradoxical symptoms that
      were not apparent in FLU patients. Patients treated with FLU showed a
      significantly lower relapse rates on days 15, 23 and 30 after the detoxification
      week. Our data provide further evidence of FLUs ability to counteract BZD
      effects, control BZD withdrawal and normalize BZD receptor function. The
      effectiveness of FLU may reflect its capacity to upregulate BZD receptors and to
      reverse the uncoupling between the recognition sites of BZD and GABA, on the
      GABA(A) macromolecular complex, that has been reported in tolerant subjects.

PMID- 14578016
TI  - Assay of salsolinol in peripheral blood mononuclear cells of alcoholics and
      healthy subjects by gas chromatography-mass spectrometry.
AB  - Endogenous 6,7-dihydroxy-1-methyl-1,2,3,4-tetrahydroisoquinoline (salsolinol)
      could be a potential marker involved in the aetiology of alcoholism. Whereas the
      amount of salsolinol in plasma and urine depends on several dietary conditions,
      the salsolinol from peripheral mononuclear cells should be formed endogenously.
      Salsolinol was quantified in lymphocytes of 10 controls and 11 alcoholics (after
      1 and 13 weeks of abstinence) using solid phase extraction and gas
      chromatography/mass spectrometry. Alcoholics showed significantly lower
      salsolinol concentration than the controls. After 13 weeks of abstinence a
      further significant decrease of SAL levels could be seen in the lymphocytes of
      alcoholics. The findings of this study support the theory that salsolinol might
      be a trait marker in alcoholism.

PMID- 14578015
TI  - Smoking addiction among university students in Istanbul.
AB  - In this study, we investigated smoking addiction and some risk factors among
      university students in Istanbul. A questionnaire survey of 236 university
      students studying in Istanbul Medical Faculty (n: 148) and other faculties (n:
      88) was performed with cross-sectional and responding-under-observation methods
      in March-May 1999. Thirty-six per cent of the university students with mean age
      24.0 (2.9 were addicted to smoking (n: 85): 41.3% males and 26.7% females; 67.5%
      were using imported and 32.5% were using local product cigarettes. Of the
      subjects, 18.1% were smoking 1-10 cigarettes a day, 61.4% 11-20 cigarettes a day
      and 20.5% more than 20 cigarettes a day. When alcohol and smoking addiction were
      compared with logistic regression analysis, with respect to gender, age, school,
      parents' educational levels, living style and the sources of income, the risk
      factor for alcohol addicts was found to be more 2.54 times than smoking addicts
      (OR = 2.54, 95% CI = 1.38-4.67; p = 0.003). The study has emphasized the
      association of alcohol and smoking addiction in university students and the
      prevalence of smoking addiction among adolescent females.

PMID- 14578017
TI  - Detection of DNA single-strand breaks and glutathione in mononuclear blood cells
      of radiotherapy technicians.
AB  - We wanted to investigate the effects of gamma radiation on DNA single-strand
      breaks (SSB) and glutathione (GSH) levels in mononuclear blood cells (MNC) of
      radiotherapy technicians. DNA SSB in MNC of radiotherapy technicians who use
      (60)Co-gamma source in their works were detected by alkaline filter elution and
      compared to control subjects. In addition, GSH levels were measured using the
      enzymatic method in MNC. Blood samples were collected from radiotherapy
      technicians on Monday and Friday. DNA SSB levels were found to be significantly
      higher in smoking controls compared to non-smoking controls. Significant
      increases of 36% and 49% in DNA SSB were detected from Monday to Friday for non
      smoking and smoking radiotherapy technicians, respectively. GSH levels were found
      to be decreased significantly from Monday to Friday. Gamma-radiation resulted in
      increased DNA SSB levels of MNC in radiotherapy technicians throughout the
      working week and these breaks have been observed to be repaired at the weekend.
      Smoking habit caused an additional increase in the SSBs observed in radiotherapy
      technicians.

PMID- 14578018
TI  - Acupuncture in the treatment of alcohol withdrawal symptoms: a randomized,
      placebo-controlled inpatient study.
AB  - Thirty-four alcoholics were treated with acupuncture to the ear and the body in a
      randomized single-blind placebo-controlled design over 14 days. Orthodox points
      and placebo needles to orthodox points were used daily for a total of 10
      treatments starting on the first day of admission as add-on therapy to standard
      medication with carbamazepine. The primary outcome was the Clinical Institute
      Withdrawal Assessment (CIWA-Ar-scale) assessed on days 1-6, 9 and 14. No initial
      differences were found regarding sociodemographic data, drinking history and
      alcohol-related data, indicating successful randomization. Longitudinal analysis
      of the Clinical Institute Withdrawal Assessment (CIWA-Ar-scale) data showed that
      patients assigned to acupuncture had a general tendency towards better outcome
      results and significantly fewer withdrawal symptoms on day 14 (Wilcoxon
      W=177.500, Z=-2.009, p = 0.045). No significant differences were found in the
      Beck Depression Inventory (BDI), State-Trait Anxiety Inventory (STAI X1 and X2)
      and Eigenschaftswoerterliste (EWL S60). We conclude that acupuncture as an
      adjunctive treatment to carbamazepine medication shows promise for the treatment
      of alcohol withdrawal symptoms. Further investigation of this treatment modality
      appears to be warranted.

PMID- 14578019
TI  - The apomorphine test: a biological marker for heroin dependence disorder?
AB  - This experimental study was conducted in the inpatient detoxification addictive
      behavior unit of the Sant Pau Hospital in Barcelona and included 22 healthy
      subjects (HS) and 42 intravenous heroin-dependent subjects (HDS). Apomorphine
      induced yawning rates were investigated in three different groups; heroin
      dependent patients stabilized on d-propoxiphene, heroin-dependent patients
      recently withdrawn from d-propoxiphene and normal controls. Yawning responses
      were recorded continuously by independent observers for periods of 45 minutes
      following administration of low doses of subcutaneous apomorphine and NaCl. The
      lowest subcutaneous apomorphine dose able to induce a significantly higher number
      of yawning responses in HS was 0.005 mg/kg. The yawning responses induced by this
      dose in HDS were also significantly higher than those induced by placebo. When
      comparing the number of yawning responses between the study groups, differences
      were observed only between HDS and HS and no effect of gender was obtained. The
      apomorphine test may be useful in assessing central dopamine system alterations
      associated with chronic heroin consumption and could be a stable and reliable
      biological marker of heroin-dependence disorders.

PMID- 14578020
TI  - Ethyl glucuronide: on the time course of excretion in urine during
      detoxification.
AB  - Ethyl glucuronide (EtG) is a promising new biological state marker of recent
      alcohol consumption that detects alcohol use reliably over a definite time
      period. Other currently available markers lack acceptable sensitivity and
      specificity. Our aim is to elucidate under naturalistic conditions the time
      course of EtG excretion in urine following alcohol consumption and to show how
      this can be utilized for monitoring and prognosis in patients. There are no other
      existing data on this issue to date. One hundred and thirty-eight urine samples
      from 28 male alcohol withdrawal patients were drawn every 3-24 hours for up to 94
      hours after hospitalization. Breath ethanol concentration (mean) at
      hospitalization was 900 mg/L. Patient age in years was 40.3 (mean). Determination
      of urine EtG was performed by gas chromatography/mass spectrometry (GC/MS) with
      deuterium-labelled EtG as an internal standard. The strongest correlations
      (p<0.01) were found between EtG determinations in the different patient when
      breath ethanol concentrations (BEC) were 0 and 48 hours after BEC=0 (r=0.747),
      EtG 24 and 48 hours after BEC=0 (r=0.872), and in the time frame of detection
      (hours) of EtG and EtG 48 hours after BEC=0 (r=0.762). No significant correlation
      was found (Mann-Whitney test) between EtG concentrations in urine at different
      time points between the groups of patients with (a) 1 or less-2, (b) 3-4 or more
      previous hospitalizations, (c) a history of seizures (yes/no) or (d) an age above
      or below the median (40.5). EtG excretion in urine is not random, but seems
      rather to follow a kinetic profile. Furthermore our preliminary data indicate,
      that there is no significant difference for EtG concentration in urine when
      correlated to group variables such as age, seizures and hospitalizations.

PMID- 14578021
TI  - Nicotine reversal effects of the benzoflavone moiety from Passiflora incarnata
      Linneaus in mice.
AB  - A benzoflavone moiety (BZF) has recently been reported to be liable for many of
      the biological effects of the plant Passiflora incarnata Linneaus. In light of
      various reports mentioning the usefulness of P. incarnata in tobacco addiction,
      studies have been performed using four doses (1, 5, 10 and 20 mg/kg) of the
      bioactive BZF moiety isolated from the aerial parts of P. incarnata. In a 7-day
      experimental regimen, mice (n = 5) were given nicotine hydrogen tartrate (2
      mg/kg), and combinations of nicotine with four doses of BZF (NnP-1, NnP-5, NnP-10
      and NnP-20) q.i.d. by the s.c. route. At the end of the 7 days of treatment,
      naloxone was given to the mice from all groups to induce a nicotine withdrawal
      syndrome. The mice that had been treated with 10 and 20 mg/kg dose of BZF
      concurrently with nicotine showed a significantly fewer number of withdrawal
      jumps relative to the group treated with nicotine alone (Nn group). Separately,
      in a 14-day treatment regimen, mice (n = 10; for the N group, n = 12) were
      administered nicotine (2 mg/kg) and combinations of nicotine with four doses of
      BZF (NP-1, NP-5, NP-10, NP-20 groups) q.i.d. by the s.c. route. Spontaneous
      physical and behavioural signs of nicotine dependence were observed 3 hours after
      cessation of treatments on the 14th day. Mice administered with combinations of
      nicotine and 5, 10 and 20 mg/kg doses of BZF (i.e. NP-5, NP10 and NP-20 groups),
      exhibited less intensity and severity of withdrawal effects compared to the mice
      treated with nicotine alone. Those mice treated with the two highest doses of
      BZF,in combination with nicotine (NP-10 and NP-20), showed significantly fewer
      nicotine-abstinence withdrawal jumps and normal ambulatory behaviour. BZF
      treatment prevented weight loss and resulted in normal performance in the
      swimming endurance test, which may be a measure of stress and/or depression.
      Similarly, acute administration of a single 20 mg/kg dose of BZF prevented some
      of the nicotine-withdrawal effects; lower doses were almost inert. These studies,
      although preliminary, suggest that the BZF may have value in treating nicotine
      addiction.

PMID- 14578022
TI  - Obesity as a cause of "false-positive" alcohol misuse laboratory investigations.
AB  - Three patients are reported with a prior history of alcohol misuse accompanied by
      abnormal liver toxicity tests and other indices of alcohol misuse. A decreased
      but persistently raised serum gamma-glutamyl transferase activity during
      subsequent abstinence or controlled drinking was interpreted incorrectly as due
      to continued alcohol misuse whereas obesity-related fatty liver was the probable
      cause. The value of serum carbohydrate deficient transferrin assays in the
      differential diagnosis of abnormal liver toxicity tests is emphasized.

PMID- 14578025
TI  - Childhood multifocal skeletal non-Hodgkin lymphoma is a differential diagnosis of
      battered child syndrome.
AB  - Skeletal lesions observed in battered children include fractures, subperiostal
      new bone formation, irregular metaphyses, and cone-shaped epiphyses. A 4-year-old
      girl presented with bone pain. Radiographs revealed multiple fractures and
      epiphyseal and metaphyseal lesions highly significant for battered child
      syndrome. Six weeks later the authors diagnosed primary multifocal skeletal non
      Hodgkin lymphoma. This case report illustrates that multifocal skeletal non
      Hodgkin lymphoma is a differential diagnosis of battered child syndrome.

PMID- 14578026
TI  - Progression of osteosarcoma after high-dose methotrexate: over-rescue by folinic
      acid.
AB  - A 16-year-old girl with a distal femur osteosarcoma became pain-free with the
      first treatment of methotrexate 12.5 g/m(2) and folinic acid 760 mg/m(2). She was
      inadvertently given 1275 mg folinic acid after the third dose. Four days later,
      pain and swelling recurred. Appreciating that this was "over rescue" rather than
      drug resistance led to the successful use of a further 8 doses of high-dose
      methotrexate when a suboptimal response was achieved with cisplatinum,
      Adriamycin, and ifosfamide. This is the first time "over rescue" has been
      documented in humans from high-dose folinic acid after methotrexate.

PMID- 14578027
TI  - Abdominal malignant mesothelioma following autologous bone marrow
      transplantation: a case report.
AB  - Secondary malignancies are a well-known late complication occurring in patients
      who undergo bone marrow transplant (BMT) during childhood. A boy with acute
      lymphoblastic leukemia experienced a BM relapse at the age of 14 years and
      underwent an autologous BMT conditioned with TBI and melphalan. Sixteen years
      later a malignant mesothelioma of the peritoneum was diagnosed. A surgical
      approach according to the Sugarbaker technique and hyperthermic peritoneal
      perfusion with CDDP and Adriamycin were performed. The patient is alive and well
      after a follow-up of 20 months. To the authors' knowledge this is the first case
      of mesothelioma as a secondary malignancy after BMT.

PMID- 14578028
TI  - Solitary eosinophilic granuloma of the third metacarpal at pediatric age.
AB  - Langerhans cell histiocytosis involves disorders previously referred to as
      "histiocytosis X" (including eosinophilic granuloma of bone, Letterer-Siwe, and
      Hand-Schuller-Christian syndrome). Eosinophilic granuloma of the hand, especially
      if solitary, is extremely rare. This is the third pediatric case reported in the
      literature with solitary eosinophilic granuloma of the hand and the second with
      metacarpal involvement. The patient's lesion was curetted and the histologic
      examination showed eosinophilic granuloma. The patient received adjuvant
      radiotherapy because of continuing mild functional impairment and fracture risk.
      At 12-month follow-up near complete recovery of the lesion was observed.
      Radiologically, there was sclerosis and remodeling of the third metacarpal. The
      patient is disease-free at 26 months.

PMID- 14578029
TI  - Thrombocytopenia in Kawasaki disease: a risk factor for the development of
      coronary artery aneurysms.
AB  - The authors report on a 2-year-old boy with atypical Kawasaki disease (KD) and
      thrombocytopenia who developed 3 coronary artery aneurysms. The mechanism of
      thrombocytopenia in KD seems to be consumption coagulopathy. Review of the 30
      reported cases of KD and thrombocytopenia revealed that this combination is more
      common in girls and in young age groups, and is associated with an increased risk
      of coronary artery aneurysm and myocardial infarction.

PMID- 14578030
TI  - Clinical and genetic studies of familial hemophagocytic lymphohistiocytosis in
      Oman: need for early treatment.
AB  - Hemophagocytic lymphohistiocytosis (HLH) embraces the frequently
      indistinguishable conditions of familial hemophagocytic lymphohistiocytosis (FHL)
      and virus-associated hemophagocytic syndrome (VAHS). Without therapy FHL is
      invariably fatal, but successful therapy, including chemotherapy and
      immunotherapy followed by bone marrow transplantation (BMT), has been presented.
      To clarify the outcome of HLH in a developing country, with regard to clinical,
      laboratory, and genetic features, a nationwide study on all patients diagnosed
      with HLH in Oman during the 5-year period 1997-2001 was performed. In 5 patients
      and their families, mutational analysis was made. Thirteen patients with HLH were
      identified, 5 of whom had clinical manifestations of central nervous system
      involvement at presentation. In none of the patients could an infectious cause be
      identified. Ten children were referred late in the disease course, and the
      concern about starting chemotherapy before exclusion of an acute viral infection
      resulted in delayed treatment in some patients. Two children were started early
      on the HLH-94-therapy followed by successful BMT in one child. In the
      successfully transplanted child, the response to intrathecal hydrocortisone
      appeared to be better than standard therapy with intrathecal methotrexate.
      Finally, a novel missense mutation in the perforin gene was identified in 2
      patients and their family members, causing a transition of proline to threonine
      at codon 89. Early diagnosis and treatment is important to improve outcome.
      Intrathecal corticosteroids may be considered, in addition to intrathecal
      methotrexate, in certain patients. Since the novel perforin mutation has been
      reported in only 2 patients from Oman, and since similar polymorphism in the
      sequencing data of the members of their families has been identified, a founder
      effect is possible in this population.

PMID- 14578031
TI  - Is agranulocytosis following infectious mononucleosis caused by autoimmunity?
AB  - A patient developed agranulocytosis after Epstein-Barr infection. Bone marrow
      examination revealed normal myelopoiesis with reduced mature neutrophil
      polymorphonuclear cells. IgG-specific antineutrophil antibodies (anti-HNA-1a)
      were found in serum and on polymorphonuclear cells, suggesting that the
      agranulocytosis after infectious mononucleosis was caused by an autoimmune
      mechanism.

PMID- 14578032
TI  - Second malignant neoplasms after primary central nervous system malignancies of
      childhood and adolescence.
AB  - The standardized incidence ratios (SIR) and cumulative incidence rates were
      determined for developing second malignant neoplasms (SMNs) after primary central
      nervous system (CNS) malignancies occurring during childhood using registry data.
      A total of 4553 cases of primary CNS malignancies were identified. Forty-six
      cases developed SMNs, 19 occurring in a previously radiated field. The SIRs of
      developing second malignant neoplasms were 6.3 and 3.1 for those cases receiving
      and not receiving radiation therapy, respectively. The 20-year cumulative
      incidences for developing SMNs were 3.3 and 1.2% for cases receiving and not
      receiving radiation therapy, respectively. Children surviving CNS malignancies
      have an increased susceptibility for SMNs.

PMID- 14578033
TI  - Factor V Leiden and prothrombin gene 20210A variant in neonatal thromboembolism
      and in healthy neonates and adults: a study in a single center.
AB  - This study was conducted to identify the prevalence of FV1691A and PT20210A
      mutations in neonates with symptomatic thromboembolism and in healthy neonates
      and adults. A review of 137 healthy neonates, 368 healthy adults, and 9 neonates
      with clinical thrombosis was done to investigate for hereditary prothrombotic
      mutations. For the neonates with thromboembolism, data were collected to reveal
      the underlying diagnosis, site of thrombosis, and associated risk factors.
      Investigations included screening for factor V 1691A and prothrombin 20210A.
      Seven of 9 neonates had one or more risk factors at the time of thromboembolism.
      Seventy percent (5/7) had underlying congenital thrombophilia (4/7 FV Leiden, 1/7
      homozygote protein C deficiency). Among the healthy population, 11.9% of the
      neonates and 9% of the adults had FV1691A mutation, 4.8% of the neonates and 2.7%
      of the adults had PT 20210A mutation. Incidence of FV1691A mutation in the
      neonates with symptomatic thromboembolism was very high. The prevalence of both
      FV1691A and PT20210A mutations were remarkably higher than previously reported.

PMID- 14578034
TI  - Retroperitoneal infantile fibrosarcoma: clinical, molecular, and therapeutic
      aspects of an unusual tumor.
AB  - The authors describe a patient with a large retroperitoneal infantile
      fibrosarcoma that responded well to preoperative chemotherapy, which subsequently
      facilitated the complete surgical resection of the mass. The patient had an
      unusual site of metastasis presumed to be to a regional lymph node. The histology
      on initial core biopsies was not classic but showed a round cell, myxoid pattern.
      The presence of the t(12;15)(p13;q25) and the fusion transcript ETV6-NTRK3 by
      RTPCR facilitated the diagnosis.

PMID- 14578035
TI  - MultiCenter outcome of pediatric oncology patients requiring intensive care.
AB  - A retrospective cohort study was conducted to evaluate the intensive care outcome
      of pediatric cancer patients between 1996 and 1998. The study comprised 20
      pediatric intensive care units (PICUs) and 802 patients with cancer requiring
      PICU care. Patients with a history of cancer were identified from PICUs
      participating in the Pediatric Intensive Care Unit Evaluations program. Their
      demographics, resource requirements, and outcomes were compared with those of
      noncancer patients. Cancer patients comprised 3.3% (802/24,431) of PICU
      admissions. Overall PICU survival was not different between cancer and noncancer
      patients (95% vs. 96%, p =.2). Cancer patients were older (99 +/- 3 vs. 72 +/- 1
      months, p <.001), had similar gender distributions, and had similar lengths of
      stay (3.3 +/- 0.2 vs. 3.9 +/- 0.1 days, p =.98). The majority (72%) were admitted
      to the PICU for postoperative care; PICU survival in these patients was 100, 100,
      and 71% for those not receiving mechanical ventilation or vasoactive agent
      infusion, those receiving either mechanical ventilation or vasoactive agent
      infusion, and those receiving both, respectively. PICU survival in nonoperative
      patients was 87% overall; survival for those requiring ventilation, vasoactive
      infusions, or both was 93, 89 and 46%. Overall hospital survival was 99% in
      operative cancer patients and 81% in nonoperative patients (p =.004, operative
      vs. nonoperative patients). Pediatric cancer patients receiving intensive care do
      well overall. Outcomes have substantially improved and, in general, the diagnosis
      of cancer should not limit the provision of intensive care. Additionally,
      resource use in terms of lengths of stay in the PICU is not different between
      cancer and noncancer patients.

PMID- 14578036
TI  - Sensitivity to radiation and alkylating agent of peripheral lymphocytes and
      fibroblasts in a Hoyeraal-Hreidarsson syndrome patient.
AB  - Hoyeraal-Hreidarsson syndrome (HHS) is a severe infantile variant of X-linked
      dyskeratosis congenita (DC). The authors report evidence of increased in vitro
      sensitivity to radiation and alkylating agent in circulating lymphocytes and
      fibroblasts obtained from a 7-year-old boy with HHS. A major telomere shortening
      was also found (3 kb) as compared to healthy donors (10 kb). The standard
      treatments, chemotherapy regimens, and radiation therapy were not possible. The
      data suggest that conditioning regimens including TBI should not be used when a
      bone marrow transplantation procedure is planned in these patients.

PMID- 14578037
TI  - Is neutropenia a clue for early diagnosis of X-linked agammaglobulinemia?

PMID- 14578038
TI  - Characterization of cellular phenotypes and cytokine expression in balt from
      children with congenital heart diseases.
AB  - The present study was performed to target and call attention to the bronchial
      associated lymphoid tissue (BALT), part of our immune system, from which, we
      believe, several forms of prophylactic and therapeutic approaches can be
      developed. The characterization of its immune components, cells, and cytokines,
      in absence of antigenic stimuli, is pioneer in literature. Eighteen cases of
      necropsies were chosen and selected the paraffin-embedded lungs. The ages of 11
      females and 7 males varied from 5 to 31 months. Cause of death: congenital heart
      diseases. EXCLUSION CRITERIA: lung infection at necropsy and/or arterial
      hypertrophy greater than Heath-Edwards' 1st degree. Immunohistochemical technique
      was applied to identify the cell phenotypes and the cytokines in situ. BALT was
      identified in all cases in this study. The main cellular phenotypes in BALT were
      T helper (TH) and B lymphocytes surrounded by T cytotoxic lymphocytes, natural
      killer cells, and dendritic cells in less quantities. Interleukin 10 and Tumor
      Necrosis Factor alpha were the predominant cytokines in BALT without antigenic
      stimuli. BALT is an important structure of the lung immune system in infants,
      with a tendency to maintain an environment favorable to the Th2 arm of immune
      response. It needs more exploration to define its behavior in front of
      infections, especially those with pulmonary tropism.

PMID- 14578039
TI  - Case report: lethal multiple pterygium syndrome.
AB  - We report a case of lethal multiple pterygium syndrome (LMPS). Intrauterine fetal
      demise was diagnosed at 31 weeks' estimated gestational age. Subsequent fetopsy
      established the diagnosis of LMPS. Macroscopic, microscopic, and radiographic
      findings in the case are discussed, and LMPS is reviewed.

PMID- 14578040
TI  - Clinico-pathologic conference: 12-year-old girl with fatigue, anemia, weight
      loss, abdominal distention, and occasional nausea and vomiting.
AB  - A clinicopathologic case is presented. The patient was a 12-year-old white girl
      with a history of fatigue and dizziness, occasional nausea and vomiting, and
      anemia, who showed abdominal distention, especially in the epigastrium. An
      epigastric mass was palpable. Gastroscopy was done, and surgery followed.
      Pertinent laboratory findings are presented, and clinical discussion follows. The
      pathology is then presented and discussed.

PMID- 14578041
TI  - Clinico-pathologic conference: newborn with hydrops fetalis caused by CMV
      infection case report.

PMID- 14578042
TI  - Pathologic quiz case: missed abortion at 6 weeks gestation.

PMID- 14578043
TI  - Protein-lipid interactions studied with designed transmembrane peptides: role of
      hydrophobic matching and interfacial anchoring.
AB  - Biological membranes are characterized by a heterogeneous composition, which is
      not only manifested in the wide variety of their components, but also in aspects
      like the lateral organization, topology, and conformation of proteins and lipids.
      In bringing about the correct membrane structure, protein-lipid interactions can
      be expected to play a prominent role. The extent of hydrophobic matching between
      transmembrane protein segments and lipids potentially constitutes a versatile
      director of membrane organization, because a tendency to avoid hydrophobic
      mismatch could result in compensating adaptations such as tilt of the
      transmembrane segment or segregation into distinct domains. Also, interfacial
      interactions between lipid headgroups and the aromatic and charged residues that
      typically flank transmembrane domains may act as an organizing element. In this
      review, we discuss the numerous model studies that have systematically explored
      the influence of hydrophobic matching and interfacial anchoring on membrane
      structure. Designed peptides consisting of a polyleucine or polyleucine/alanine
      hydrophobic stretch, which is flanked on both sides by tryptophan or lysine
      residues, reflect the general layout of transmembrane protein segments. It is
      shown for phosphatidylcholine bilayers and for other model membranes that these
      peptides adapt a transmembrane topology without extensive peptide or lipid
      adaptations under conditions of hydrophobic matching, but that significant
      rearrangements can result from hydrophobic mismatch. Moreover, these effects
      depend on the nature of the flanking residues, implying a modulation of the
      mismatch response by interfacial interactions of the flanking residues. The
      implications of these model studies for the organization of biomembranes are
      discussed in the context of recent experiments with more complex systems.

PMID- 14578044
TI  - Mutational analysis of the major proline transporter (PrnB) of Aspergillus
      nidulans.
AB  - PrnB, the l-proline transporter of Aspergillus nidulans, belongs to the Amino
      acid Polyamine Organocation (APC) transporter family conserved in prokaryotes and
      eukaryotes. In silico analysis and limited biochemical evidence suggest that APC
      transporters comprise 12 transmembrane segments (TMS) connected with relatively
      short hydrophilic loops (L). However, very little is known on the structure
      function relationships in APC transporters. This work makes use of the A.
      nidulans PrnB transporter to address structure-function relationships by
      selecting, constructing and analysing several prnB mutations. In the sample, most
      isolated missense mutations affecting PrnB function map in the borders of
      cytoplasmic loops with transmembrane domains. These are I119N and G120W in L2
      TMS3, F278V in L6-TMS7, NRT378NRTNRT and PY382PYPY in L8-TMS9 and T456N in L10
      TMS11. A single mutation (G403E) causing, however, a very weak phenotype, maps in
      the borders of an extracellular loop (L9-TMS10). An important role of helix TMS6
      for proline binding and transport is supported by mutations K245L and,
      especially, F248L that clearly affect PrnB uptake kinetics. The critical role of
      these residues in proline binding and transport is further shown by constructing
      and analysing isogenic strains expressing selected prnB alleles fused to the gene
      encoding the Green Fluorescent Protein (GFP). It is shown that, while some prnB
      mutations affect proper translocation of PrnB in the membrane, at least two
      mutants, K245E and F248L, exhibit physiological cellular expression of PrnB and,
      thus, the corresponding mutations can be classified as mutations directly
      affecting proline binding and/or transport. Finally, comparison of these results
      with analogous studies strengthens conclusions concerning amino acid residues
      critical for function in APC transporters.

PMID- 14578045
TI  - ATP and GSH dependence of MRP1-mediated outward translocation of phospholipid
      analogs in the human erythrocyte membrane.
AB  - The active outward translocation of phospholipid analogues from the inner to the
      outer membrane leaflet of human erythrocytes by the multi-drug resistance protein
      MRP1 (ABCC1) depends on intracellular reduced glutathione (GSH). Entrapment of
      ATP and increasing amounts of GSH inside resealed ghosts prepared from
      erythrocytes resulted in an up to six-fold increase of the translocation rate.
      Entrapped oxidized glutathione (GSSG) acted inhibitory but produced stimulation
      after addition of the disulphide-reducing reagent dithioerythritol. Modification
      of GSH by esterification of the C-terminal carboxylate of Gly, removal of the N
      terminal Glu or substitution of the SH group by an anionic S-dicarboxyethyl or
      sulphonate group abolished stimulation. The effect of S-alkylation of GSH
      depended on the length of the alkyl group. S-methyl GSH was somewhat more
      effective than GSH, but maximal stimulation was similar. S-butyl GSH acted poorly
      stimulatory while S-hexyl GSH was essentially ineffective. Analyses of the
      kinetic data of translocation revealed K(m) values for GSH and methyl-GSH of
      respectively 7.4 +/- 2.4 and 4.9 +/- 1.1 mmol l(-1). At high GSH levels and
      defined constant ATP levels using an ATP-regenerating system, the Km for ATP of
      the outward translocation was 0.16 +/- 0.02 mmol l(-1). In the same system
      lacking GSH, the Km for ATP of the inward translocation by the aminophospholipid
      flippase was 0.53 +/- 0.23 mmol l(-1).

PMID- 14578046
TI  - Structural and functional characterization of the human NBC3 sodium/bicarbonate
      co-transporter carboxyl-terminal cytoplasmic domain.
AB  - The sodium bicarbonate co-transporter, NBC3, is expressed in a range of tissues
      including heart, skeletal muscle and kidney, where it modulates intracellular pH
      and bicarbonate levels. NBC3 has a three-domain structure: 67 kDa N-terminal
      cytoplasmic domain, 57 kDa membrane domain and an 11 kDa C-terminal cytoplasmic
      domain (NBC3Ct). The role of C-terminal domains as important regulatory regions
      is an emerging theme in bicarbonate transporter physiology. This study determined
      the functional role of human NBC3Ct and characterized its structure using
      biochemical techniques. The NBC3 C-terminal domain deletion mutant (NBC3DeltaCt)
      had only 12 +/- 5% of wild-type transport activity. This low activity is
      attributable to low steady-state levels of NBC3DeltaCt and almost complete
      retention inside the cell, as assessed by immunoblots and confocal microscopy,
      suggesting a role of NBC3Ct in cell surface processing. To characterize the
      structure of NBC3Ct, amino acids 1127-1214 of NBC3 were expressed as a GST fusion
      protein (GST.NBC3Ct). GST.NBC3Ct was cleaved with PreScission Protease and native
      NBC3Ct could be purified to 94% homogeneity. Gel permeation chromatography and
      sedimentation velocity ultracentrifugation of NBC3Ct indicated a Stokes radius of
      26 and 30 angstroms, respectively. Shape modelling revealed NBC3Ct as a prolate
      shape with long and short axes of 19 and 2 nm, respectively. The circular
      dichroism spectra of NBC3Ct did not change over the pH 6.2-7.8 range, which rules
      out a large change of secondary structure as a component of pH sensor function.
      Proteolysis with trypsin and chymotrypsin identified two proteolytically
      sensitive regions, R1129 and K1183-K1186, which could form protein interaction
      sites.

PMID- 14578047
TI  - Mixed lipid aggregates containing gangliosides impose different 2H-NMR dynamical
      parameters on water environment depending on their lipid composition.
AB  - Water dynamics in samples of ceramide tetrasaccharide (Gg4Cer) vesicles and GM1
      ganglioside micelles at 300:1 water/lipid mole ratio were studied by using
      deuterium nuclear magnetic resonance (2H-NMR). GM1 imposes a different
      restriction on water dynamics that is insensitive to temperatures either above or
      below its phase transition temperature or below the freezing point of water. The
      calculated correlation times are in the range of 10(-10) s, typical of water
      molecules near to the polar groups. Pure GM1 micelles have two distinct water
      microenvironments dynamically characterized. Their dynamic parameters remain
      constant with temperature ranging from -18 to 32 degrees C, but the amount of
      strongly associated water is modified. By contrast, a mixture of single soluble
      carbohydrates corresponding to GM1 polar head group does not preserve the dynamic
      parameters of water hydration when the temperature is varied. Incorporation of
      cholesterol or lysophosphatidylcholine into GM1 micelles substantially increases
      the mobility of water molecules compared with that found in pure GM1 micelles.
      The overall results indicate that both the supramolecular organization and the
      local surface quality (lipid-lipid interaction) strongly influence the
      interfacial water mobility and the extent of hydration layers in
      glycosphingolipid aggregates.

PMID- 14578048
TI  - Voltage-dependent ionic conductances in the human malignant astrocytoma cell line
      U87-MG.
AB  - Although the human malignant astrocytoma cell line U87-MG has been used in
      numerous studies, few findings are available on the properties of its membrane
      ion conductances. Characterization of the ion channels expressed in these cells
      will make it possible to study membrane ion conductance changes when a receptor
      is activated by its ligand. This will help to elucidate the functional properties
      of these receptors and their signal-transduction pathways in pathophysiological
      events. This work studied the voltage-dependent ionic conductances of U87-MG
      cells using the Whole-Cell Recording patch-clamp technique. Six types of voltage
      dependent ionic currents were identified: (i) a TEA-, 4-AP- and CTX-sensitive
      Ca2+-dependent K+ current, (ii) a transient K+ current inhibited by 4-AP, (iii)
      an inwardly rectifying K+ current blocked by Ba2+ and 4-AP, (iv) a DIDS- and SITS
      sensitive Cl- current, (v) a TTX-sensitive Na+ conductance and (vi) a L-type Ca2+
      conductance activated by BayK-8644 and inhibited by Ni and the L-type Ca2+
      channel inhibitor, nifedipine. In addition, electrical depolarizations elicited
      inward currents due to voltage-independent, Ca2+-dependent K+ influx against the
      electrochemical gradient, probably via an ouabain-sensitive Na+-K+ pump.

PMID- 14578049
TI  - Fluorescence evidence for a loose self-assembly of the fusion peptide of
      influenza virus HA2 in the lipid bilayer.
AB  - Steady state fluorescence experiments were performed on a 25-mer synthetic
      peptide incorporated in the phospholipid vesicle to study the role of
      oligomerization of the fusion peptide in membrane fusion. It was found from
      fluorescence resonance energy transfer (FRET) that the extent of lipid mixing and
      the initial mixing rate varied with the fusion peptide concentration in a higher
      than linear fashion, indicating that the peptide promoted membrane mixing as
      oligomers. Results of self-quenching of the Rhodamine (Rho) in Rho-labelled
      peptide incorporated in the phospholipid bilayer indicated that the peptide
      molecules assembled in the bilayer with an order higher than dimer. The data also
      revealed that the peptides were not tightly packed in the membrane. Binding
      affinity measurement monitored by the NBD fluorescence intensity on the
      fluorophore-labelled fusion peptide supports the notion of self-association of
      the peptide in the vesicular dispersion. In the sodium dodecyl sulphate
      polyacrylamide gel electrophoresis (SDS-PAGE) experiments, a diffuse band with
      apparent molecular mass close to a dimeric species of the wild type fusion
      peptide suggested that the fusion peptides formed loose oligomers under the
      influence of SDS detergent in the electric field. The result is in contrast to a
      less fusion-active variant which appears to exhibit less propensity for self
      association.

PMID- 14578050
TI  - Comparison of the effectiveness of the Hanen Parent Programme and traditional
      clinic therapy.
AB  - BACKGROUND: Both direct (clinician to child) and indirect (clinician to carer)
      approaches are currently used in the management of children with language delay,
      but there is as yet little evidence about their relative effects or resource
      implications. AIMS: This research project compared the Hanen Parent Programme
      (HPP) in terms of its effectiveness and consequent suitability for an inner-city
      UK population with clinic-based, direct intervention. METHODS & PROCEDURES:
      Thirty-seven children aged 2;06-3;06 years with a diagnosis of language
      impairment and their parents took part in the research project. The children were
      allocated on a geographical basis to receive therapy either as part of an HPP or
      in a clinic. Nineteen children and their families took part in one of the five
      Hanen groups that ran successively over 16 months; 18 children and their families
      received clinic-based intervention. The children's language was assessed using
      the PLS-3 (UK version) and from an analysis of audio-taped parent and child
      interaction at three assessment points, one pretherapy and two post-therapy over
      12 months. Two parent language measures were also analysed. OUTCOMES & RESULTS:
      Significant gains in language scores were shown by 71% of the children over 12
      months. There were no statistically significant differences in child language
      scores between the two therapy groups at any assessment point. However, the HPP
      was twice as intensive (in terms of therapist time) as clinic therapy based on
      average group size, which has resource implications. CONCLUSIONS. Results suggest
      that there are parent and child factors that need consideration when choosing an
      appropriate intervention programme for a child with language impairment. Parental
      expectations, existing interaction style and the level of child language may be
      important influencing factors.

PMID- 14578051
TI  - Prosody in autism spectrum disorders: a critical review.
AB  - BACKGROUND: Many individuals with autism spectrum disorders present with unusual
      or odd-sounding prosody. Despite this widely noted observation, prosodic ability
      in autism spectrum disorders is often perceived as an under-researched area.
      AIMS: This review seeks to establish whether there is a prosodic disorder in
      autism, what generalizations can be made about its various manifestations and
      whether these manifestations vary according to the diagnosis. A literature review
      was carried out to establish what areas of prosody in autism spectrum disorders
      have been researched to date, what the findings have been and to determine what
      areas are yet to be researched. MAIN CONTRIBUTION: It is shown that prosody in
      autism spectrum disorders is an under-researched area and that where research has
      been undertaken, findings often conflict. The findings of these conflicting
      studies are compared and recommendations are made for areas of future research.
      CONCLUSIONS: Research in this area has covered mostly prosodic expression,
      although some more recent studies cover comprehension, processing and the
      relationship of receptive prosodic ability to theory of mind. Findings conflict
      and methodology varies greatly.

PMID- 14578052
TI  - Providing an equitable service to bilingual children in the UK: a review.
AB  - BACKGROUND: The UK is a multicultural, multilingual society and the majority of
      paediatric speech and language therapists in England have at least one bilingual
      child on their caseload. There are many imperatives driving the profession to
      provide an equitable service for bilingual children. Evidence is beginning to
      emerge, however, that bilingual children with specific language impairment are
      not being identified and are, therefore, not accessing services. The situation
      facing clinicians in the UK is not unique: it is mirrored around the world. AIMS:
      This paper reviews the literature relating to speech and language services for
      bilingual children and begins by providing an overview of the forces driving the
      need to provide equity of service. All aspects of the therapeutic process are
      then examined, from referral to therapy, in order to identify features that are
      regarded as best practice. Whilst the focus is on delivery of services in the UK,
      research findings from around the world are considered. MAIN CONTRIBUTION:
      Certain themes emerged during the review and their implications are discussed. In
      particular, the need for assessment tools, training and research is highlighted.
      CONCLUSIONS: Features indicative of best practice are highlighted and tentative
      suggestions made that would enable services to address the challenges of serving
      bilingual paediatric caseloads.

PMID- 14578053
TI  - Protection from harm: the experience of adults after therapy with prolonged
      speech.
AB  - BACKGROUND: It is well documented that adults can control stuttering if they use
      certain novel speech patterns referred to generically as prolonged-speech (PS).
      These speech patterns were refined in the 1960s and developed into behavioural
      treatment programmes. The bulk of available PS treatment research has focused on
      speech parameters thought to reflect favourable treatment outcome. Considering
      this, and that post-treatment relapse is known to be common, clinicians and
      researchers could be usefully informed by knowledge about the experiences of
      those who receive these treatments. Subsequently, they could use such information
      in attempts to control stuttering in their clients. Yet, at present, systematic
      research on this topic is scant. AIMS: The continued development of PS treatments
      could be usefully informed by research into the experiences of those who use PS
      to control stuttering. Hence, that is the topic of the present report. METHODS &
      PROCEDURES: The method used was phenomenology. Participants were a purposive
      sample of 10 people who had received PS treatment. During a 2-year period, a
      collaborative approach to the study of the topic was developed between the
      participants and interviewer. Interviews were from 1.5 to 2 hours, and a total of
      34 interviews and discussions were undertaken with participants. Transcripts of
      these were used to generate text from which themes were identified using line-by
      line, holistic and selective approaches. OUTCOMES & RESULTS: The main findings
      were that even after therapy with PS there is a continued risk of stuttering
      occurring, and although adults have the novel experience of controlling
      stuttering, they also continue to experience feeling different from those who do
      not stutter, which may be exacerbated after therapy. Given the negative
      consequences associated with stuttering and feeling different, the essence of the
      experience after therapy with PS is that adults use their own resources to
      integrate behavioural skills with existing experiences in order to protect
      themselves from the harm of stuttering as best they can. PS changes speech, but
      not the dynamic and often unpredictable communication situations of everyday
      life. Hence, the maximum benefits of PS are attained when clients use a strategic
      approach to control stuttered speech and daily communication. CONCLUSIONS: These
      findings are consistent with the results of existing outcome research as well as
      with other current research from the present group. Their implications are
      discussed in relation to the structure of PS treatments as well as in relation to
      future PS outcome research. The clinical implications of these findings are
      discussed in terms of informing prospective clients of the experiential
      consequences of PS, selecting clients who might benefit from PS and in terms of
      assisting clients to achieve optimal benefits from PS.

PMID- 14578054
TI  - Oral diadochokinetic rates for normal Thai children.
AB  - BACKGROUND: The diadochokinetic (DDK) rate represents an index for assessing
      motor skills. It is commonly used in routine clinical evaluation of diseases of
      the central nervous system, disturbances of the peripheral sensory motor
      formations and immaturity of the speech mechanism. Oral DDK rates are a popular
      guideline for the assessment, diagnosis and treatment of patients with a
      neurological deficit of the speech mechanism. Baseline DDK rates have been
      published for English-speaking children, but not for Thai-speaking children.
      Thailand is situated in South East Asia, and the language belongs to the
      monosyllabic, tonal, Sino-Tibetan group with extensive multisyllabic borrowings
      from the non-tonal, Pali-Sanskrit group. AIMS: To assess the oral DDK rates for
      normal Thai children aged between 6 and 13 attending primary schools in order to
      establish a baseline for assessing, diagnosing and treating patients. METHODS &
      PROCEDURES: Subjects included 197 students who repeated, in rapid succession,
      specified sounds representing different levels of physiologic complexity, as
      indicated by differences in the developmental schedule, articulatory placement
      and syllabic content. Twenty syllable repetitions were required for monosyllabic
      utterances, 15 for bisyllablics and 10 for trisyllablics. Visi Pitch Analysis was
      used to calculate the average time that subjects took to produce the sounds.
      OUTCOMES & RESULTS: The time taken for the lip functions /pe,Cyrillic/, /a:-u:/,
      /u:-i/ and /i:-a:/ averaged 4.55, 6.67, 7.53 and 7.27 seconds, respectively. The
      tongue functions /te,Cyrillic/, /le,Cyrillic/, /ke,Cyrillic/ and click averaged
      4.58, 4.82, 4.85 and 5.87 seconds, respectively. Tongue movement side-to-side
      between the corners of the mouth averaged 8.73 seconds, while the lip-tongue
      functions /pe,Cyrillic-te,Cyrillic/, /pe,Cyrillic-ke,Cyrillic/ and /pe,Cyrillic
      te,Cyrillic-ke,Cyrillic/ were 6.97, 7.52 and 6.85 seconds, respectively. Sex and
      age influenced oral DDK time. The findings differ from those reported for English
      speaking children. CONCLUSIONS: A basis for assessment of children with
      neuromotor deficits or oral structure impairment is provided for both Thai and
      South East Asian children with similar physiological development and languages
      with similar sounds.

PMID- 14578058
TI  - Inter-rater reliability and concurrent validity of step length and step width
      measurement after traumatic brain injury.
AB  - PURPOSE: To determine the inter-rater reliability and concurrent validity of step
      length and step width measurement after traumatic brain injury. METHOD: Twelve
      people with traumatic brain injury completed six comfortable and six fast paced
      walking trials over a 10 m distance. Step length and step width were measured by
      five observers using two procedures. First, using pens taped on the subjects'
      heels which marked the floor at each heel strike and a tape measure. Second, by
      videotaping the subjects' feet as they walked on a mat marked with 5 cm grids and
      using a computer program to digitize foot position and calculate step length and
      width. RESULTS: The inter-rater reliability of step length and width measurements
      was very high, with intraclass correlation coefficients between 0.94 and 1.00,
      for both procedures. Concurrent validity was excellent, with correlations between
      the procedures ranging from 0.93 to 1.00. However, attaching pens to the heels
      did cause a slight reduction in right step length and walking speed when walking
      at a fast or comfortable pace, respectively. CONCLUSIONS: Assessing step length
      and width using pens taped to the subjects' heels and a tape measure is a
      reliable and valid clinical measure after traumatic brain injury.

PMID- 14578060
TI  - External validation of a housing recommendation model for clients following
      stroke rehabilitation.
AB  - PURPOSE: Using a Social Judgment Theory approach, mathematical models of clinical
      decisions can be developed to predict new decisions. However, since these models
      are often developed under 'laboratory conditions' using hypothetical cases rather
      than real world client samples, questions may be raised concerning the external
      validity of such models. The purpose of this research was to validate a discharge
      housing decision making model developed with hypothetical clients with stroke
      with a real sample. This process is referred to as external validation. METHODS:
      Cross-tabulations were performed to compare the model discharge housing
      prediction against the team's actual recommendations for 60 clients from three
      rehabilitation centres. A sensitivity and specificity analysis was used to
      compare the model predictions against the client's actual discharge housing.
      RESULTS: A simple mathematical model was constructed to accurately predict
      housing recommendations. However, the predictive power of the model appeared to
      be limited by clinician/team consideration of unmeasured factors such as client
      personality and motivation. CONCLUSION: It is suggested that the housing decision
      model developed may be useful for rehabilitation teams as a starting point when
      discussing the best place to recommend a client reside on discharge from
      rehabilitation. Such a model may assist teams to standardise their decision
      processes and minimise the potential for unwarranted bias.

PMID- 14578059
TI  - The efficacy of a work-station intervention programme to improve functional
      ability and flexibility in ageing clients with Cerebral Palsy: a pilot study.
AB  - PURPOSE: Health care workers associated with the long-term care of ageing clients
      with Cerebral Palsy have reported on the adverse effects of less active daily
      activity programmes with resultant decreased functional mobility. While the
      negative effects of ageing have been reported in these clients, programmes have
      not been implemented to determine whether these adverse changes can be reversed
      or prevented. The efficacy of a work-station intervention programme to improve
      functional ability and flexibility in ageing clients with cerebral palsy was
      investigated. METHOD: A clinical intervention study using repeated measures
      (pre/post-intervention and at follow-up) to evaluate efficacy was undertaken.
      Twenty-two clients with Cerebral Palsy participated in a twice-weekly work
      station programme delivered over 8 weeks. The Physical Mobility Scale items, two
      upper limb function measures, range limitation of hip and knee extension and
      gleno-humeral movement were assessed. RESULTS: Results showed a significant
      improvement that was retained at follow-up in functional but not flexibility
      measures. CONCLUSION: The efficacy of a work-station exercise programme for
      ageing clients with Cerebral Palsy was demonstrated. Evidence was provided that
      the PMS is effective in showing level of dependency for these clients.

PMID- 14578061
TI  - Lower limb joint moment during walking in water.
AB  - PURPOSE: Walking in water is a widely used rehabilitation method for patients
      with orthopedic disorders or arthritis, based on the belief that the reduction of
      weight in water makes it a safer medium and prevents secondary injuries of the
      lower-limb joints. To our knowledge, however, no experimental data on lower-limb
      joint moment during walking in water is available. The aim of this study was to
      quantify the joint moments of the ankle, knee, and hip during walking in water in
      comparison with those on land. METHOD: Eight healthy volunteers walked on land
      and in water at a speed comfortable for them. A video-motion analysis system and
      waterproof force platform were used to obtain kinematic data and to calculate the
      joint moments. RESULTS: The hip joint moment was shown to be an extension moment
      almost throughout the stance phase during walking in water, while it changed from
      an extension- to flexion-direction during walking on land. The knee joint moment
      had two extension peaks during walking on land, whereas it had only one extension
      peak, a late one, during walking in water. The ankle joint moment during walking
      in water was considerably reduced but in the same direction, plantarflexion, as
      that during walking on land. CONCLUSIONS: The joint moments of the hip, knee, and
      ankle were not merely reduced during walking in water; rather, inter-joint
      coordination was totally changed.

PMID- 14578062
TI  - A functional assessment methodology for alcohol dependent patients undergoing
      rehabilitative treatments.
AB  - PURPOSE: We propose a functional assessment approach for patients with alcoholic
      dependence of working age undergoing aerobic training. The background is the WHO
      indication (ICIDH-2) to use measurable 'activities' as a means to assess the
      individual 'participation' in social life which also implies work capacity.
      Defining sustainable energetic levels for the individual is an important issue
      for both the quantification of an effective training and the evaluation of
      possible improvements following training. METHODS: Fifty-six 'alcohol dependent'
      patients, as defined by DSM IV (Diagnostic and Statistical Manual of Mental
      Disorders), admitted to our Unit in a 16 month-period participated in the study.
      Eighteen healthy subjects served as controls (Group C). Out of all the 56
      patients, 33 (Group A) underwent an aerobic training and 23 subjects (Group N)
      underwent the same pharmacological and psychological therapy but without aerobic
      training. Patients were assigned to the treatment (A) or no treatment (N) group
      according to a 'quasi-experimental' design (i.e. temporal selection criteria).
      The evaluation protocol consisted of submaximal symptom-limited tests. The tests
      consisted of bouts of 'basic' activities (walking, lifting, arm-work) to be
      performed at different intensities. We estimated the total energetic work (TW)
      performed in the tests by means of formulas available in the literature. The
      maximal energetic intensity (EI) reached during the tests was also estimated and
      expressed in MET (multiple of the basal metabolism). RESULTS: Significant
      differences in work capacity were observed between patients and healthy subjects
      at baseline. Group A significantly increased TW after rehabilitation, while Group
      N did not increment their performance at the re-test. CONCLUSIONS: The proposed
      approach could be useful in the functional assessment of deconditioned subjects
      with alcohol dependence in working age, and could monitor the changes in work
      capacity following training.

PMID- 14578063
TI  - Services for aphasia, other acquired adult neurogenic communication and
      swallowing disorders in the United Kingdom, 2000.
AB  - PURPOSE: We developed a questionnaire designed to determine the state of services
      provided by the National Health Service within the UK for adults with acquired
      neurologically caused communication disorders. A further aim was to compare our
      results with those from a similar survey conducted 10 years ago by Mackenzie et
      al. METHOD: We sent questionnaires to 264 managers and directors of adult speech
      and language therapy services in the UK. We asked questions about staffing
      levels, regional variations, patterns of service delivery at acute and chronic
      stages and staff time spent working with different communication and swallowing
      problems. RESULTS: Nearly 53% of average staff time was spent working with
      swallowing disorders accompanying neurological damage (dysphagia) compared to 24%
      with aphasia. As the percentage of time spent working with swallowing increased,
      the percentage of time spent working with aphasia reduced. Out of the time spent
      on aphasia treatment, 48% averages less than 3 h per week duration and just 4.8%
      averages more than 3 h per week, which was correlated with total number of speech
      and language therapists employed by a service. We found a significant difference
      only between London, with the highest total staff numbers, and the South West,
      with the lowest. We also found significant relationships between staff numbers
      and population size and staff numbers and the level of referrals to the service.
      CONCLUSIONS: Our main conclusions are: (1) while there may have been an increase
      in the number of speech and language therapists working with acquired and
      progressive neurogenic conditions in the past 10 years, they are mainly working
      with swallowing disorders, and (2) findings agree with recent studies showing
      that the amount of treatment or therapy that aphasic clients receive is well
      below that recommended by the literature.

PMID- 14578064
TI  - Functional evaluation of vascular hemiparetics and traditional Japanese houses.
AB  - PURPOSE: To study the functional status of vascular hemiparetics in outpatient
      clinics in Japan. METHOD: Following five functional tasks were evaluated to (1)
      pick up a pencil from the floor, (2) stand up from the floor, (3) sit up
      straight, (4) squat, (5) ambulate as far as possible. Patients were asked whether
      they added handrails and used a bed or a Japanese Futon. RESULTS: Sixty-three of
      85 patients were able to pick up a pencil from the floor and to stand up from the
      floor. Patients with poor motor recovery of the lower extremities were able get
      into and out of a bathtub as well as patients with good motor recovery. All
      patients who could not ambulate for more than 100 m and could not stand up from
      the floor began to use beds after their strokes. CONCLUSIONS: Ninety-five per
      cent of patients who could stand up from the floor were able to get into and out
      of bathtubs. All of the patients who could not stand up from the floor started to
      use beds.

PMID- 14578073
TI  - FilaBavi, a demographic surveillance site, an epidemiological field laboratory in
      Vietnam.
AB  - BACKGROUND: This Supplement to the Scandinavian Journal of Public Health brings
      together a collection of community-based studies for which the common denominator
      is a demographic surveillance site, FilaBavi, established in northern Vietnam in
      1999. This introductory paper sets out some of the background to FilaBavi as well
      as setting the scene for the individual studies.

PMID- 14578074
TI  - Patterns of mortality in Bavi, Vietnam, 1999-2001.
AB  - AIMS: Demographic data including detailed mortality patterns for Vietnam are
      relatively sparse, mainly coming from national census data. This paper describes
      detailed mortality findings from a sample drawn from the population of one
      district of northern Vietnam, over the three-year period 1999-2001. METHODS:
      These data were based on quarterly household visits to collect data on vital
      events, covering 142,318 person-years of observation over a three-year period.
      RESULTS: Crude mortality was 5.1 per 1,000 person-years (4.7 for females and 5.6
      for males). Infant mortality was 21.6 per 1,000 live births and crude birth rate
      was 14.7 per 1,000. Life expectancy at birth was 75.2 years (78.8 year for
      females and 71.1 for males). Residents of mountainous and highland areas
      experienced lower mortality than riverside and island dwellers. CONCLUSIONS:
      These findings are discussed in the light of two major demographic factors: the
      legacy of the Vietnam War and, more recently, the effect of Vietnam's two-child
      policy. Although these mortality estimates seem low, there is good reason to
      believe that they accurately reflect the current state of this population.
      Vietnam as a whole enjoys low mortality in relation to its socioeconomic status
      compared with neighbouring countries.

PMID- 14578075
TI  - Community-based assessment of unintentional injuries: a pilot study in rural
      Vietnam.
AB  - AIMS: Although unintentional injuries are recognised as a major public health
      problem globally, little is known about their patterns and rates at the community
      level in most low-income countries. Rapid social development, leading to
      increased traffic and industrialization, may be changing patterns of injury.
      Injuries within the home environment have not so far been recognized to the same
      extent as traffic and work-related injuries in Vietnam, largely because they have
      not been effectively counted. This study took place in northern Vietnam, in the
      context of a longitudinal community surveillance site called FilaBavi, as a pilot
      project aiming to determine the community incidence of unintentional injury and
      to explore appropriate methods for community-based injury surveillance. METHODS:
      An initial study population of 23,807 was identified and asked about their
      experience of injury in the preceding three months. RESULTS: Overall 450 new
      injuries were detected over 5,952 person-years, a rate of 76 per 1,000 person
      years. Males were injured at 1.6 times the rate of females, and home and road
      traffic accidents were most common. Most injuries occurred during unpaid
      household tasks. Cutting and crushing injuries occurred most frequently. Of 221
      deaths from all causes in the FilaBavi population during 1999 among 43,444 person
      years, 25 were attributed to unintentional injuries and two to suicide.
      Unintentional injury was the third leading cause of death in this community, with
      a case-fatality rate of 0.8%. DISCUSSION: The findings suggest that greater
      attention needs to be directed toward the prevention of injuries occurring in the
      home in rural Vietnam. On the basis of this pilot study, a one-year study using
      the same approach is under way to characterize the patterns of unintentional
      injury in more detail, including any seasonal variation.

PMID- 14578076
TI  - The role of health economics in Vietnam: a tentative research agenda.
AB  - Little health economics research has been done in developing countries,
      reflecting the fact that 10% of the world's health research is devoted to 90% of
      the world's health problems. Healthcare in developing countries relies more on
      market mechanisms than healthcare in developed countries. From a health
      economist's point of view, there are reasons to suspect that healthcare systems
      in many developing countries are both inefficient and inequitable. The public
      healthcare model in Europe offers better solutions to the problems in developing
      countries than the private health care model in the USA. In this article aspects
      of the health economics situation in Vietnam are discussed and some important
      health economics research questions identified.

PMID- 14578077
TI  - FilaBavi and the future of community-based health research in Vietnam.

PMID- 14578078
TI  - More is not necessarily better: Examining the nature of the temporal reference
      memory component in timing.
AB  - Three experiments compared the timing performance of humans on a modified
      temporal generalization task with 1, 3, or 5 presentations of the standard
      duration. In all three experiments subjects received presentations of a standard
      duration at the beginning of a trial block and then had to judge whether each of
      a number of comparison stimuli was or was not the standard. The duration of the
      standard changed between blocks. The three experiments varied the experimental
      design (between or within subjects), task difficulty (how closely the comparison
      stimuli were spaced around the standards), and presence or absence of feedback on
      performance accuracy. Number of presentations of the standard never affected the
      proportion of identifications of the standard when it was presented, nor other
      features of the temporal generalization gradients observed. The implications for
      the operation of reference memories within the scalar timing system were explored
      via models that made different assumptions about how the individual presentations
      of the standard were stored and used.

PMID- 14578079
TI  - Secondary task difficulty modulates forward blocking in human contingency
      learning.
AB  - The influence of a secondary task on forward blocking of human contingency
      ratings was examined. A smaller blocking effect was found when participants
      performed a highly demanding secondary task than when they performed a less
      demanding secondary task. The modulatory effect of secondary task difficulty was
      significant only when the secondary task was administered during both the
      learning and the test phase of the contingency judgement task. The results
      suggest that forward blocking in human contingency learning cannot be fully
      accounted for by associative processes. Instead, forward blocking seems to depend
      at least partially on deliberate deductive reasoning processes.

PMID- 14578080
TI  - Inhibitory conditioning in honeybees.
AB  - Honeybees were rewarded with sucrose solution for choosing AX(a grey target, X,
      labelled with a distinctive stimulus, A) rather than ABX (a grey target labelled
      both with A and with another distinctive stimulus, B)-AX+/ABX- training. Tests of
      independent groups made after such training showed a clear preference not only
      for AX over ABX, but also for ABX over BX, and for X over BX. These experiments,
      along with some earlier ones to which they bring a new perspective, provide
      persuasive evidence, previously lacking, of inhibitory conditioning in honeybees.

PMID- 14578081
TI  - Interaction between preexposure and overshadowing: further analysis of the
      extended comparator hypothesis.
AB  - Three experiments with rats used conditioned suppression of barpress to test
      predictions of the extended comparator hypothesis, which assumes that the
      effectiveness of (first-order) comparator stimuli in modulating responding to a
      target conditioned stimulus (CS) is itself modulated by other (second-order)
      comparator stimuli. Experiment 1 demonstrated that both pretraining exposure to
      the target CS alone (i.e., CS-preexposure effect, also known as latent
      inhibition) and pretraining exposure to a compound of the target CS and nontarget
      CS (i.e., compound-CS-preexposure effect) counteract overshadowing, and that
      posttraining deflation (i.e., extinction) of the overshadowing stimulus
      attenuates responding to the target CS when overshadowing is preceded by a CS
      preexposure treatment (i.e., yields a CS-preexposure effect), but not when
      overshadowing is preceded by a compound-CS-preexposure treatment. Experiment 2
      examined the consequences of posttraining associative inflation of the
      overshadowing stimulus or the preexposure companion stimulus following conjoint
      compound-CS-preexposure and overshadowing treatment. Experiment 3 examined the
      consequences of posttraining inflation of the overshadowing stimulus or the
      context following conjoint CS-alone preexposure and overshadowing treatment. The
      results support the expression-focused comparator view in contrast to recent
      acquisition-focused models of retrospective reevaluation.

PMID- 14578082
TI  - Disruption of verbal STM by irrelevant speech, articulatory suppression, and
      manual tapping: do they have a common source?
AB  - Under appropriate conditions, immediate serial verbal recall is impaired by
      irrelevant speech, articulatory suppression, and syncopated tapping.
      Interpretation of these variables in terms of the phonological loop component of
      working memory assumes separate phonological storage and articulatory rehearsal
      processes. In contrast, the Object-Oriented Episodic Record (O-OER) of Jones and
      the feature theory of Neath interpret these and other phenomena in terms of a
      unitary multimodal system. Three experiments investigate these disrupting tasks,
      with each experiment emphasizing one parameter. In each case, recall of
      phonologically similar and dissimilar letter sequences is compared as a marker of
      the presence or absence of phonological coding. In Experiment 1, subjects heard
      or articulated a single item, or tapped a single key at equal intervals. Only
      articulatory suppression impaired performance; it also abolished the effects of
      phonological similarity. Experiment 2 was identical, except that items were
      heard, or generated in a syncopated rhythm. Both suppression and tapping impaired
      performance to an equivalent extent and obliterated the effect of phonological
      similarity. Syncopated irrelevant speech caused a modest but significant
      impairment in performance. Experiment 3 was identical to Experiment 1, except
      that six tokens were used. Irrelevant speech and tapping had a clear impact on
      recall, but neither removed the phonological similarity effect. Again
      articulatory suppression had a major impact on performance and removed the effect
      of phonological similarity. We conclude that the pattern of results readily fits
      the phonological loop hypothesis, provided one accepts Saitos proposal that
      generating syncopated sequences uses common processes with speech production. It
      is not clear how the results can be explained by either the O-OER or the feature
      hypothesis.

PMID- 14578083
TI  - Directly assessing the relationship between irrelevant speech and articulatory
      suppression.
AB  - Larsen and Baddeley (2003) examine whether the disruption caused by articulatory
      suppression on immediate memory tasks is similar to or different from the
      disruption caused by irrelevant speech. Based on experiments in which they test
      whether the phonological similarity effect is present or absent, they conclude
      that articulatory suppression and irrelevant speech are different. We assessed
      whether articulatory suppression and irrelevant speech are similar or different
      by correlating the disruption each causes. A significant correlation obtained,
      indicating a relation between the two. These apparently different conclusions can
      be readily resolved by adopting the view that articulatory suppression,
      irrelevant speech, and many other factors vary in the degree to which they are
      likely to cause subjects to abandon reliance on phonological/acoustic cues in
      particular tasks.

PMID- 14578084
TI  - Reification of phonological storage.
AB  - We question the arguments and data presented by Larsen and Baddeley (this issue
      2003) in support of the phonological loop account of verbal short-term memory on
      a number of grounds. These include the correlation between effect size and the
      presence of a phonological similarity effect in the data, and the existence
      elsewhere in the literature of effects of articulatory suppression and
      interference between verbal and nonverbal information that undermines the
      phonological loop account. We question the idea that short-term memory phenomena
      are best conceived of in terms of phonological storage, and we sketch an
      alternative perspective that does not rely on the notion of a bespoke
      phonological store, an entity that we argue represents a reification.

PMID- 14578085
TI  - The irrelevant sound effect: what needs modelling, and a tentative model.
AB  - This paper reviews the literature on the irrelevant sound effect and concludes
      that, contrary to some claims, the data consistently show that irrelevant sound
      and articulatory suppression are not functionally equivalent. We evaluate the
      contribution of Larsen and Baddeley (2003 in this issue) and briefly discuss
      additional data in support of their position. We perform an error analysis on
      data from their third experiment and simulate detailed aspects of those data
      using our primacy model of immediate serial recall. Our model is briefly related
      to a number of findings in the literature on irrelevant sound.

PMID- 14578087
TI  - Selective interference with verbal short-term memory for serial order
      information: a new paradigm and tests of a timing-signal hypothesis.
AB  - Many recent computational models of verbal short-term memory postulate a
      separation between processes supporting memory for the identity of items and
      processes supporting memory for their serial order. Furthermore, some of these
      models assume that memory for serial order is supported by a timing signal. We
      report an attempt to find evidence for such a timing signal by comparing an item
      probe task, requiring memory for items, with a list probe task, requiring memory
      for serial order. Four experiments investigated effects of irrelevant speech,
      articulatory suppression, temporal grouping, and paced finger tapping on these
      two tasks. In Experiments 1 and 2, irrelevant speech and articulatory suppression
      had a greater detrimental effect on the list probe task than on the item probe
      task. Reaction time data indicated that the list probe task, but not the item
      probe task, induced serial rehearsal of items. Phonological similarity effects
      confirmed that both probe tasks induced phonological recoding of visual inputs.
      Experiment 3 showed that temporal grouping of items during list presentation
      improved performance on the list probe task more than on the item probe task. In
      Experiment 4, paced tapping had a greater detrimental effect on the list probe
      task than on the item probe task. However, there was no differential effect of
      whether tapping was to a simple or a complex rhythm. Overall, the data illustrate
      the utility of the item probe/list probe paradigm and provide support for models
      that assume memory for serial order and memory for items involve separate
      processes. Results are generally consistent with the timing-signal hypothesis but
      suggest further factors that need to be explored to distinguish it from other
      accounts.

PMID- 14578088
TI  - The time course of negative repetition effects in post-cue naming.
AB  - It has previously been shown that when picture pairs are repeated across blocks
      in a post-cue naming task, former distractors are named faster than former
      targets: the "negative repetition effect" (Mayall, Humphreys, & Kotsanis, 2002).
      In the present study the time course of this effect was examined. Experiment 1
      demonstrated that the effect became apparent after a lag of only two intervening
      trials, with former targets being named faster than former distractors after a
      lag of zero trials. Experiment 2 used a new baseline condition with repeated
      picture pairs for which no response was required on the first presentation.
      Comparisons with this baseline indicated that the negative repetition effect is
      the result of suppression of former targets as opposed to facilitation of former
      distractors. The results support the proposal of Mayall et al. that the negative
      repetition effect reflects a form of speech monitoring that is applied when there
      is competition in the process of mapping from semantics to name representations.

PMID- 14578089
TI  - The interplay of stop signal inhibition and inhibition of return.
AB  - Inhibition of return (IOR) refers to slower responding to a stimulus that appears
      in the same rather than a different location as that of a preceding stimulus. The
      goal of the present study was to examine the relationship between IOR and stop
      signal inhibition. Participants were presented with two stimuli (S1 and S2) on
      each trial. On half of the trials (go trials), participants were required to make
      a speeded button-press response to report the location of S1; on the other half
      of trials (stop trials), they were required to cancel the response to S1, as
      indicated by the appearance of a stop signal at a variable delay (stop signal
      delay, SSD) after the appearance of S1. Success in cancelling an S1 response
      varied directly as a function of the SSD: The longer the delay, the more
      difficult it was for participants to cancel the prepared response. We examined
      the magnitude of IOR in the S2 reaction times as a function of whether
      participants made a correct go response to S1, made an erroneous non-cancelled
      response to S1, or successfully cancelled a response to S1. Our results indicated
      that the presentation of a stop signal increased the magnitude of IOR, even when
      the S1 response was not successfully cancelled. However, this was true only when
      the to-be-cancelled response involved the same effectors as the response used to
      reveal IOR. These results suggest that there may be a motor component to IOR that
      is sensitive to the same inhibitory processes that are used to cancel responses
      in a stop signal paradigm.

PMID- 14578090
TI  - Distinct mechanisms account for the linear non-separability and conjunction
      effects in visual shape encoding.
AB  - In a series of visual search experiments involving simple 2D shapes, Arguin and
      Saumier (2000) showed that targets that were made of conjunctions of distractor
      features or that were a linear combination of distractor features were searched
      at significantly slower rates than single-feature linearly separable targets. The
      present study assessed whether these conjunction and linear nonseparability
      effects can be attributed to distinct mechanisms. Specifically, we studied the
      impact of target-distractor similarity on the search rates for single-feature,
      conjunction, and linearly nonseparable targets. The results replicate the
      conjunction and linear nonseparability effects obtained by Arguin and Saumier.
      They also show that the conjunction and linear separability effects are
      differently modulated by variations in target-distractor similarity. This
      dissociation demonstrates that both effects are based on distinct mechanisms. The
      possible nature of these mechanisms is discussed.

PMID- 14578092
TI  - Acitretin suppression of squamous cell carcinoma: case report and literature
      review.
AB  - Retinoids have been used for the treatment and suppression of cutaneous
      malignancies in patients with basal cell nevus syndrome, xeroderma pigmentosum,
      and in patients with recurrent skin cancers as a result of immunosuppression for
      renal transplantation. We report a 40-year-old male who began to develop multiple
      squamous cell carcinomas of the skin after treatment with PUVA for severe
      psoriasis. The numbers of squamous cell carcinomas increased when acitretin was
      discontinued and decreased when he was taking the drug at a dose of 25 mg daily.
      Acitretin should be considered as a maintenance therapy for psoriasis patients
      developing squamous cell carcinomas as a result of PUVA therapy.

PMID- 14578093
TI  - Transition from methotrexate and cyclosporine to other therapies including
      retinoids, ultraviolet light and biologic agents in the management of patients
      with psoriasis.
AB  - Patients with psoriasis typically face longterm therapy for their chronic
      disease. Often, the therapeutic agents that physicians use to treat them may
      become less effective or may cause safety or toxicity issues. The clinician must
      then decide the next therapy for his/her patient and assess benefit/risk of the
      next therapeutic agent or combination. In moving the patient from one therapy to
      the next, specific characteristics of the transition must be assessed, and how to
      stop the existing therapy, and introduce the new agent(s). The decision making
      process must take into account the longterm risks to the patient. This article
      focuses on the transition for patients with psoriasis being managed with
      methotrexate and cyclosporine to retinoids, phototherapy, and newer agents.

PMID- 14578094
TI  - Retrospective study of the efficacy of narrowband UVB and acitretin.
AB  - BACKGROUND: In this retrospective analysis the effect of narrowband ultraviolet B
      treatment in combination with acitretin is reviewed in 40 patients with plaque
      psoriasis. Narrowband UVB is highly effective for plaque psoriasis, but requires
      multiple phototherapy treatments, making patient compliance problematic. Oral
      acitretin is moderately effective as monotherapy, but when combined with
      ultraviolet B or PUVA, its use has reduced the number of treatments required for
      clearing, and has resulted in clearing of patients otherwise refractory to these
      phototherapeutic modalities. There is only sparse data on the combination of
      acitretin with narrowband UVB. We therefore analyzed data on 40 patients treated
      with this combination. RESULTS: The majority of patients treated had psoriasis
      that was refractory to treatment with broadband ultraviolet B, monotherapy with
      narrowband UVB, monotherapy with acitretin, or the combination of acitretin and
      broadband UVB. In this difficult-to-treat group of patients, the combination of
      low dose acitretin (25 mg po daily) and narrowband UVB three times per week
      resulted in greater than 75% improvement in 29 (72.5%) patients. Only 5 (12.5%)
      patients had less than 50% improvement. The combination was well tolerated and
      associated with typical retinoid and narrowband UVB side effects including
      elevation of serum lipids, burn and cheilitis. CONCLUSION: The combination of
      acitretin with narrowband UVB results in faster improvement even in more
      difficult-to-treat patients. In combination the treatments appear to have
      synergistic effects.

PMID- 14578095
TI  - Retrospective analysis of the treatment of psoriasis of the palms and soles.
AB  - In this retrospective analysis, the effect of currently used treatments in 26
      patients with psoriasis of the palms and soles were analyzed. In general,
      patients are treated initially with topical medications including superpotent
      topical corticosteroids in combination with calcipotriene ointment or tazarotene
      gel or both. If satisfactory improvement is not achieved in 4-8 weeks, systemic
      retinoids are added, formerly etretinate and currently acitretin, except in women
      of childbearing potential. If the latter regimen is not effective within two
      months, soak PUVA is added to the regimen of oral retinoids and topical
      medications. If improvement is inadequate, or if the treatment regimen is not
      tolerated, methotrexate or cyclosporine have been added in the past. The
      availability of the excimer laser has recently modified our approach so that this
      therapy is used in combination with acitretin before soak PUVA. With the
      availability of biologic agents, methotrexate is avoided because of its
      hepatotoxicity and bone marrow toxicity and cyclosporine is avoided because of
      its nephrotoxicity. If oral acitretin plus topical therapy is not adequate to
      control the disease and the excimer laser is not an option because of its limited
      availability, alefacept, etanercept and infliximab are added when possible. Other
      biologic agents are likely to be added to this list in the future.

PMID- 14578096
TI  - Case studies in severe psoriasis: A clinical strategy.
AB  - Individuals with moderate-to-severe psoriasis perceive that the disease exerts
      profound emotional, social and physical effects on their lives, and a significant
      percentage report that they do not consider their treatment sufficiently
      aggressive. A survey of individuals with a variety of chronic diseases reveals
      that those with psoriasis have the lowest estimation of their health-related
      quality of life, lower than that of patients with arthritis, congestive heart
      failure, chronic lung disease or depression. Although psoriasis can be treated
      effectively, many treatments are associated with long-term risks. Toxicity
      sparing treatment strategies that include combination, rotational and sequential
      regimens can help to control moderate-to-severe psoriasis while reducing risk.
      Algorithms for the treatment of moderate-to-severe psoriasis detail possible
      options for specific types of psoriasis and for patients with specific needs. The
      purpose of the algorithms is to make optimum use of phototherapy, traditional
      cytotoxic and immunosuppressive agents, retinoids, and newer biologic agents.

PMID- 14578097
TI  - A comparison of ex vivo expanded DCs derived from cord blood and mobilized adult
      peripheral blood plastic-adherent mononuclear cells: decreased alloreactivity of
      cord blood DCs.
AB  - BACKGROUND: Cord blood (CB) has been used as an alternative source of
      transplantable allogeneic stem cells for a variety of malignant and non-malignant
      diseases. However, we have demonstrated delayed recovery of T- and B-cell
      function, and T-cell subsets post unrelated CB transplantation (UCBT), and
      deficiencies of CB mononuclear cells (MNC) in producing cytokines, including G
      CSF, GM-CSF, M-CSF, IL-12, and IL-15. In this study we have investigated the ex
      vivo generation of DC from CB versus mobilized adult peripheral blood (APB) for
      later use as adoptive cellular immunotherapy. METHODS: CB and APB-adherent MNC
      were cultured in serum-free media with GM-CSF IL-4, FLT-3 ligand, tumor growth
      factor-beta (TGF-beta), and tumor necrosis factor-alpha (TNF-alpha) for 7 days.
      Morphology, phenotype, immunohistochemistry, clonogenic activity, and
      alloreactivity in MLR were evaluated. RESULTS: CB and APB monocyte-derived ex
      vivo expanded DC expressed similar DC markers CD83 (31.27+ 11.7% versus 34.0+
      5.2%, CB versus APB), CD1a (23.4+ 4.2% versus 27.6+ 6.3%), and CD80 (21.97+
      12.01% versus 27.7+ 5.95). Immunohistochemistry showed that cells with DC
      morphology expressed CDla but not CD14. Neither FLT-3 ligand nor TGF-fl enhanced
      DC expansion. Addition of 10% autologous plasma to CB cultures promoted greater
      cell survival and a 150% increase in CDla + /CD80+ cell recovery. CB DC were 62%
      as effective stimulators of adult allogeneic T-cels as APB DC (p < .05) in
      allogeneic MLR. DISCUSSION: While phenotypically similar, CB and APB DC have
      differential potency in allogeneic MLR, which may account for the difference in
      GvHD and infection incidence and severity between UCBT and allogeneic stem cell
      transplantation, and may require a different approach for adoptive cellular
      immunotherapy. The mechanism(s) associated with these differences require further
      elucidation.

PMID- 14578098
TI  - Adipose-derived adult stem cells: isolation, characterization, and
      differentiation potential.
AB  - Adipose tissue is an abundant, accessible, and replenishable source of adult stem
      cells that can be isolated from liposuction waste tissue by collagenase digestion
      and differential centrifugation. These adipose-derived adult stem (ADAS) cells
      are multipotent, differentiating along the adipocyte, chondrocyte, myocyte,
      neuronal, and osteoblast lineages, and can serve in other capacities, such as
      providing hematopoietic support and gene transfer. ADAS cells have potential
      applications for the repair and regeneration of acute and chronically damaged
      tissues. Additional pre-clinical safety and efficacy studies will be needed
      before the promise of these cells can be fully realized.

PMID- 14578099
TI  - Cryopreservation of cord blood after liquid storage.
AB  - BACKGROUND: The processing of cord blood may result in delays prior to RBC
      depletion and cryopreservation. The overall objective of this investigation is to
      determine the influence of liquid storage prior to cryopreservation on the post
      thaw viability. METHODS: UC blood supplemented with CPD anticoagulant (CB) was
      obtained from normal donors with informed consent. CB was stored undiluted, or
      diluted with 1:1 ratio of storage solution STM-sav for up to 72 h. The undiluted
      control samples were stored at room temperature. CB samples supplemented with STM
      sav were stored at 4 degrees C. After completion of the storage protocol, the
      sample was RBC depleted, frozen, stored, thawed, and assayed for viability.
      Nucleated cell counts, percentage of CD34+ cells, and frequency of colony
      formation were determined during liquid storage and after cryopreservation.
      RESULTS: The post-thaw mononuclear cell recovery and viability of cord blood
      stored for 72 h was significantly lower than that of cord blood stored for 24 h
      prior to cryopreservation. This difference was true for cord bloods stored in STM
      sav and controls. Dilution of the cord blood with STM-sav improved the frequency
      of CFU-GM observed. DISCUSSION: Liquid storage of cord blood for 24 h prior to
      cryopreservation does not adversely influence the post-thaw cell recovery. The
      use of a storage solution (STM-Sav) enhances the retention of colony-forming
      capabilities post-thaw. These and other studies provide an important foundation
      for the development of integrated protocols for cord blood banking.

PMID- 14578100
TI  - Microbial contamination of cellular products for hematolymphoid transplantation
      therapy: assessment of the problem and strategies to minimize the clinical
      impact.
AB  - BACKGROUND: Hematopoietic progenitor stem cells (HPSC) are a specialized
      transfusion product used for transplantation. Microbial contamination may occur
      during harvest or subsequent manipulation of these cells. The same difficulties
      in ensuring a safe, sterile, final product are faced in the preparation of other
      cell-therapy products directly obtained from donors. Detection of contamination
      is problematic, and the clinical significance of infusing contaminated HPSC is
      controversial. METHODS: Chimeric Therapies' manufacturing and clinical experience
      with BM HPSC products and validation of a culture method for detection are
      described. In addition, this paper reviews the literature concerning contaminated
      blood products, including rates and circumstances of contamination, organisms,
      methods of detection, and the clinical significance of infusion of contaminated
      products. RESULTS: Seven of 33 BM harvest products received at Chimeric Therapies
      were culture positive for skin commensal organisms. Three of seven were culture
      positive in the infused product. This compares with literature reports of 0-42%.
      No patients had significant infusion reactions or evidence of infection related
      to the contamination. DISCUSSION: The risks associated with microbial
      contamination with skin commensals are insignificant compared with other
      components of transplantation. Contamination with pathogens can be eliminated
      with careful good manufacturing practices (GMP). A series of practical
      recommendations are presented for the reduction of contamination in HPSC and cell
      therapy products.

PMID- 14578101
TI  - Monocyte enrichment from leukapharesis products for the generation of DCs by
      plastic adherence, or by positive or negative selection.
AB  - BACKGROUND: DCs for use in immunotherapy are frequently generated from peripheral
      blood monocytes. However, there are different approaches to monocyte enrichment.
      METHOD: Plastic adherence is a widely used method for the enrichment of monocytes
      collected in a leukapheresis procedure. Alternatively,monocytes may be enriched
      by positive selection using magnetic beads coupled to CD14 Abs, or by cell
      depletion using beads coupled to Abs against CD2 and CD19 to remove non
      monocytes. RESULTS: Positive selection resulted in the highest purity of immature
      DCs (97 +/- 1%), but in a low yield (8 +/- 3%). In contrast, depletion of non
      monocytes gave a good yield (21 +/- 6%), but insufficient purity (42 +/- 10%).
      Conventional adherence procedures resulted in a good yield (25 +/- 5%) and
      reasonable purity (72 +/- 4%). All three monocyte enrichment procedures resulted
      in DCs that underwent maturation upon exposure to a combination of
      lipopolysaccharide and IFN-gamma. These DCs had a typical immune phenotype, they
      released similar amounts of IL-12, and had the capacity to support MLR.
      CONCLUSION: Our data provide a basis to choose a monocyte enrichment procedure
      that favors high purity or a high yield. However, if a manual open system
      suffices, plastic adherence is a reasonable alternative.

PMID- 14578102
TI  - Generation of confluent cardiomyocyte monolayers derived from embryonic stem
      cells in suspension: a cell source for new therapies and screening strategies.
AB  - BACKGROUND: Cellular cardiomyoplasty is evolving as a new strategy to treat
      cardiac diseases. A prerequisite is a reliable source of pure cardiomyocytes,
      which could also help in the exploitation of recent advances in genomics and drug
      screening. Our goal was to establish a robust lab-scale process for the
      generation of embryonic stem (ES)-cell-derived cardiomyocytes in suspension.
      METHODS: A 71 ES cell clone carrying a construct consisting of the alpha-cardiac
      myosin heavy chain (alphaMHC) promoter driving the neomycin resistance gene was
      used for antibiotic-driven cardiomyocyte enrichment. Rotating suspension culture
      was established to initiate embryoid body (EB) formation. To track growth and
      differentiation kinetics, cell count and flow cytometry for SSEA-I, E-cadherin
      (stem-cell marker)and sarcomeric myosin (cardiomyocytes marker) was performed.
      Oct4 expression was measured via real time (RT)-PCR. RESULTS: Cultures comprising
      2.5-8 x 10(6) differentiating FS cells/mL were obtained after 9 days in rotating
      suspension. Upon G418 addition,vigorous contracting spheres, termed cardiac
      bodies (CB), developed. These cultures consisted of about 2.1 x 10(5) enriched
      cardiomyocytes/mL after 6- 10 days of selection. Suspensions comprising 90-
      95%viable single cells were generated using an improved dissociation method.
      Seeding of cardiomyocytes with 7 x 10(4) cell/cm(2) resulted in a homogeneous
      monolayer of synchronously contracting cells. Myocyte specific
      immunohistochemistry indicated purity of > 99%. DISCUSSION: We have established a
      reliable lab-scale protocol to generate cultures of highly enriched
      cardiomyocytes in suspension. This will facilitate development of larger-scale
      processes for stem-cell based cardiomyocyte supply. An improved method is
      provided to derive vital suspensions of cardiomyocytes, which could be utilized
      for transplantation as well as for drug screening purposes.

PMID- 14578103
TI  - HPC enumeration with the Sysmex XE-2100 can guide further flow cytometric CD34(+)
      measurements and timing of leukaphereses.
AB  - BACKGROUND: The aim of this study was to evaluate whether HPC counts measured
      with the hematology analyzer can predict CD34+ levels in peripheral blood and in
      the apheresis product, as detected by standard flow cytometry. The main focus was
      the evaluation of HPC counts in poor mobilizers. METHODS: Progenitor cell
      quantification was performed measuring HPC counts provided by the Sysmex XE-2100
      hematology analyzer and CD34+ counts obtained in parallel by flow cytometry.
      Peripheral blood of patients who had received chemotherapy and G-CSF (142
      measurements) and healthy donors mobilized with G-CSF alone (106 measurements)
      was investigated HPC counts in peripheral blood were also correlated with
      apheresis yield. RESULTS: HPC counts were significantly higher than CD34+ counts
      (3.5 fold inpatients and 1.7 fold in healthy donors, p= 0.0015). Our data
      indicate that HPC counts < or = 10/microL in pretreated patients predict a low
      probability of adequate CD34+ counts in peripheral blood and yields < 2 x
      10(6)/kg in subsequent aphereses. Furthermore, repetitive low HPC enumerations in
      an individual were followed by insufficientCD34+ counts in peripheral blood or
      aphereses in 81% of investigations. In healthy donors low HPC counts (< or =
      10/microL; 12/106 measurements) did not exclusively predict low CD34+ counts
      (median 23/microL). DISCUSSION: HPC counts can be used to schedule the start of
      CD34+ measurements(threshold > 10 HPC/microL) in patients mobilized after
      chemotherapy for autologous donation. Thus, expensive and time-consuming CD34+
      enumerations can perhaps be minimized HPC measurements cannot completely replace
      flow cytometric CD34+ enumeration. In particular healthy stem-cell donors should
      be monitored with both methods to exclude false negative HPC measurements.

PMID- 14578106
TI  - Bovine serum albumin modified the intracellular distribution and improved the
      antiviral activity of an oligonucleotide.
AB  - In the present work, we describe the ability of bovine serum albumin (BSA) to
      improve the cytoplasmatic delivery of a phosphodiester oligonucleotide (PO),
      whose phosphorotioate analogue is ISIS 2922 (Vitravene). The changes in intensity
      and lambda(max) in fluorescence spectroscopy and the increase in fluorescence
      anisotropy upon complex formation between the oligonucleotide and the protein (PO
      BSA) were used to determine the dissociation constant, Km=6.3 x 10(-8) M. The
      stoichiometry of the complex is mainly 1:1, although 2 PO per BSA have been
      detected at high PO/BSA ratios. The complexation did not protect PO against
      enzymatic degradation by snake venom phosphodiesterase (0.1 mg/mL). Fluorescence
      microscopy revealed that PO-BSA complexes showed a decreased uptake and modified
      pattern of intracellular distribution with a rapid nuclear accumulation (rather
      than vesicular localization in the cytoplasm observed for free oligonucleotide).
      The effect was only observed over a certain threshold of BSA concentration
      (higher than found in media supplemented with 10% serum). By this way, the
      interaction with albumin increased the antiviral activity of the oligonucleotide,
      tested by a plaque reduction assay in MRC-5 fibroblasts infected with human
      cytomegalovirus (strain RC 256) at a MOI of 0.0035. At 10 microM PO
      concentration, free PO decreased virus plaques to 85% of the control, while PO
      BSA complexes reduced to 60%, in the same order than ISIS 2922. The
      phosphorotioate analogue complexed by BSA (ISIS 2922-BSA) showed the highest
      activity with 45% of the control plaques.

PMID- 14578104
TI  - Collection of autologous PBSC in patients with polycythemia vera.
AB  - BACKGROUND: Allogeneic stem-cell transplantation (SCT) can eradicate
      myelofibrosis (MF), but is limited by donor availability and toxicity. We
      previously reported normalization of counts and resolution of MF after ablative,
      syngeneic SCT in spent phase polycythemia vera (PV). Hence, GvL is not required
      to eradicate MF. Autologous SCT may advance treatment for spent phase PV by
      restoring effective hematopoiesis. The influence of organomegaly,
      myelosuppression and MF on PBSC collection has not been studied in the setting of
      PV. METHODS: Sixteen patients with PV underwent PBSC collection. Mobilization was
      with filgrastim alone, with a target cell content of 2.5 x 10(6) CD34(+)/kg. All
      myelosuppression was discontinued 2 weeks prior to collection. RESULTS: Median
      ages at diagnosis and collection were 47 and 57 years, respectively.
      Organomegaly, MF and use of myelosuppressive therapies were present in 10 (63%),
      4 (25%) and 7 (44%) patients. Median total nucleated cells (TNC) and CD34(+)
      counts were 8.3 x 10(8)/kg and 4.98 x 10(8)/kg. MF had an adverse effect on TNC
      (p=0.05) but not on the CD34(+) content. Time from diagnosis and the use of
      myelosuppresion had no influence on TNC and CD34(+) contents. Four patients had
      CD34(+) contents <2.5 x 10(6)/kg. Complete blood count (CBC) parameters were not
      predictive of CD34(+) content. DISCUSSION: Autologous PBSC collection is feasible
      in PV several years after diagnosis. Organomegaly and MF are not absolute
      contraindications for collection. Discontinuing myelosuppresion for 2 weeks
      before mobilization appears sufficient to collect adequate numbers of CD34(+)
      progenitors.

PMID- 14578107
TI  - Nucleic acid-matrix attachment recognition regions--as facilitators in plasmid
      transfer.
AB  - Non-viral gene transfer is an alternative to viral vectors for gene transfer.
      However, non-viral transgene expression remains undesirably low and transient.
      Matrix attachment regions (MARs) are DNA elements that are defined by their high
      affinity for the nuclear matrix. MARs may also be related to long-term transgene
      expression in vitro. The purpose of this research is to evaluate human interferon
      beta MARs element in various cell types. This was accomplished by constructing
      MARs-containing plasmid DNA (pDNA) and comparing their transgene expression with
      non-MARs-containing pDNA. We found that MARs-containing pDNA increased and
      prolonged the expression in Chinese hamster ovary (CHO) cells, but not in human
      neuroblastoma cells (SKnSH) and neuronal cells (primary neuron, astroglia and
      microglia). From the cotransfection experiment, MARs-containing pDNA had a trans
      effect on another pDNA expression. A PCR method was used to monitor the
      intracellular distribution of pDNA after cellular fractionalization. We found
      that non-MAR containing pDNA demonstrates similar intracellular distribution as
      non-MARs-containing pDNA.

PMID- 14578108
TI  - Kinetic modeling of triamterene intestinal absorption and its inhibition by folic
      acid and methotrexate.
AB  - The aim of this work was to study the intestinal absorption process of
      triamterene in situ in rats in order to gain insight on its absorption mechanism.
      The study shows an example of application of a pharmacokinetic model for drug
      disappearance from a compartment by simultaneous first order and Michaelis-Menten
      processes to the intestinal drug disappearance by absorption in a non-steady
      state system. The parameter used to quantify absorption was the absorption rate
      constant, determined in situ by means of a loop perfusion technique, performed in
      colon and in whole small intestine of rat at three pHs (5.00, 7.00 and 8.00) and
      in the presence of folic acid and methotrexate. Different concentrations of the
      drug were perfused in each condition. The concentrations versus time data were
      modeled with different kinetic absorption and inhibition differential equations
      to obtain the passive and active transport components and to elucidate the
      inhibition mechanisms. The results obtained confirm that triamterene is absorbed
      by means of passive diffusion and by a transporter or transporters related to
      folates. Folic acid and methotrexate are able to inhibit triamterene absorption.
      The results do not allow the selection of a competitive or non-competitive model
      for inhibition and this fact could be due to the presence of different carriers.
      The possibility of the existence of a secretion process sensitive to verapamil is
      also discussed.

PMID- 14578109
TI  - Plasma protein adsorption of Tween 80- and poloxamer 188-stabilized solid lipid
      nanoparticles.
AB  - The plasma proteins adsorbing onto intravenously injected carriers are considered
      to be crucial factors determining the organ distribution. Plasma protein
      adsorption patterns were analyzed on solid lipid nanoparticles (SLN) stabilized
      with Tween 80 or stabilized with poloxamer 188. The binding patterns were
      determined by applying two different sample preparation methods, i.e. removal of
      the SLN from the plasma by (a) centrifugation and (b) gel filtration to assess,
      if the separation method has an effect on the patterns obtained. The Tween 80
      modified SLN adsorbed the major plasma proteins known from particles with blood
      brain barrier specificity. Poloxamer 188-surface modified SLN adsorbed the
      proteins known from model particles that exhibit prolonged circulation time in
      the blood. It is concluded that the biodegradable SLN stabilized with Tween 80
      can potentially be used as drug carriers to the blood-brain barrier having a
      relatively long residence time in the blood stream. For the poloxamer 188
      stabilized SLN a relatively long resistance time in the blood is predicted
      leading to potential accumulation in the bone marrow when looking at the distinct
      CII/CIII adsorption.

PMID- 14578110
TI  - Synthesis, characterization and in vitro evaluation of dimethyl-beta-cyclodextrin
      4-biphenylylacetic acid conjugate.
AB  - Biphenylylacetic acid (BPAA) was linked to the free hydroxyl group of 2,6-di-O
      methyl-beta-Cyclodextrin (DM-beta-CyD) through an ester linkage to obtain the
      site specific release of the drug to the colon. The conjugate at 1:1 mole ratio
      was separated from the reaction mixture by semipreparative reverse-phase HPLC and
      characterized by 1H-NMR, 13C-NMR, IR spectroscopy, mass spectrometry and
      elemental analysis. Chemico-physical characteristics, such as water solubility
      and dissolution rate, were evaluated comparatively to the BPAA-DM-beta-CyD
      inclusion complex. Hydrolysis rates were investigated in media simulating gastro
      intestinal fluids and at pH 7.4 in the presence of porcine liver esterase. A
      rapid release of the drug was observed at acid pH value. In all cases a first
      order kinetic was observed, characterized by t1/2 value of 1.19, 19 and 4 h for
      chemical hydrolysis at pH 1.1, at pH 7.4 and enzymatic hydrolysis, respectively.
      In vitro permeation studies through caco-2 cells confirmed the ability of DM-beta
      CyD to increase the absorption of included BPAA. A slow permeation was observed
      for the drug conjugate to DM-beta-CyD due to the slow release of BPAA.

PMID- 14578112
TI  - Effect of particle size on the pharmacokinetics of menatetrenone incorporated in
      O/W lipid emulsions prepared with hydrogenated castor oils and soybean oil in
      rats.
AB  - Previously, we prepared lipid emulsions with soybean oil (SO; 20%) as oil phase
      and hydrogenated castor oils (HCOs; 2.4%) as emulsifiers (SO(20)/HCOs(2.4)), and
      found that the lipid emulsions prepared with HCO of 10 oxyethylene units
      (SO(20)/HCO10(2.4)) were quickly cleared from the plasma, while those prepared
      with HCO of 20 oxyethylene units (SO(20)/HCO20(2.4)) showed prolonged plasma
      circulation of the incorporated drug (Ueda et al., 2003). In the present study,
      the pharmacokinetics of menatetrenone incorporated into SO/HCO10s and SO/HCO20s
      of different particle sizes (100-280 nm), obtained by altering the SO contents,
      were examined in rats. The plasma half-lives of menatetrenone as SO/HCO10s were
      similar to each other, irrespective of particle size, even though the liver
      uptake of menatetrenone as SO(2.5)/HCO10(2.4) was larger than that as
      SO(20)/HCO10(2.4). The menatetrenone half-lives were also similar to each other
      for SO/HCO20s. The pretreatment with dextran sulfate 500,000 (DS500), a
      suppressor of the reticuloendothelial system (RES), increased the plasma
      concentration and inhibited the liver uptake of menatetrenone as SO/HCO10s, but
      not for those as SO/HCO20s. These findings indicated that the particle sizes did
      not affect the minimum oxyethylene units within HCOs for the prolonged plasma
      circulation of menatetrenone as SO/HCOs, which was 20.

PMID- 14578113
TI  - Immunomodulator tuftsin augments antifilarial activity of diethylcarbamazine
      against experimental brugian filariasis.
AB  - In the present study, we evaluated the potential of an immunomodulator tuftsin in
      increasing the efficacy of liposomised diethylcarbamazine (DEC) against
      experimental filarial infection of Brugia malayi. The liposomised form of DEC,
      when used at sub-optimal dose of 25 mg/kg body weight, successfully eliminated
      filarial parasite from systemic circulation in animals inflicted with B. malayi
      infection. However, the formulation was effective upto 60 days post infection
      only, followed by recurrence of the infection. In contrast, the co-administration
      of liposomal formulation of DEC along with an immunomodulator tuftsin was found
      to be competent enough to suppress microfilarial stage of parasite till 90 days
      post treatment. Interestingly, tuftsin bearing DEC liposomes were found to be
      effective against adult parasite as well.

PMID- 14578114
TI  - Humid heat acclimation does not elicit a preferential sweat redistribution toward
      the limbs.
AB  - We tested the hypothesis that local sweat rates would not display a systematic
      postadaptation redistribution toward the limbs after humid heat acclimation.
      Eleven nonadapted males were acclimated over 3 wk (16 exposures), cycling 90
      min/day, 6 days/wk (40 degrees C, 60% relative humidity), using the controlled
      hyperthermia acclimation technique, in which work rate was modified to achieve
      and maintain a target core temperature (38.5 degrees C). Local sudomotor
      adaptation (forehead, chest, scapula, forearm, thigh) and onset thresholds were
      studied during constant work intensity heat stress tests (39.8 degrees C, 59.2%
      relative humidity) conducted on days 1, 8, and 22 of acclimation. The mean body
      temperature (Tb) at which sweating commenced (threshold) was reduced on days 8
      and 22 (P < 0.05), and these displacements paralleled the resting thermoneutral
      Tb shift, such that the Tb change to elicit sweating remained constant from days
      1 to 22. Whole body sweat rate increased significantly from 0.87 +/- 0.06 l/h on
      day 1 to 1.09 +/- 0.08 and 1.16 +/- 0.11 l/h on days 8 and 22, respectively.
      However, not all skin regions exhibited equivalent relative sweat rate elevations
      from day 1 to day 22. The relative increase in forearm sweat rate (117 +/- 31%)
      exceeded that at the forehead (47 +/- 18%; P < 0.05) and thigh (42 +/- 16%; P <
      0.05), while the chest sweat rate elevation (106 +/- 29%) also exceeded the thigh
      (P < 0.05). Two unique postacclimation observations arose from this project.
      First, reduced sweat thresholds appeared to be primarily related to a lower
      resting Tb, and more dependent on Tb change. Second, our data did not support the
      hypothesis of a generalized and preferential trunk-to-limb sweat redistribution
      after heat acclimation.

PMID- 14578115
TI  - Impaired substance P release from renal sensory nerves in SHR involves a
      pertussis toxin-sensitive mechanism.
AB  - Stretching the renal pelvic wall activates renal mechanosensory nerves by a PGE2
      mediated release of substance P via activation of the cAMP-PKA pathway. Renal
      pelvic ANG II modulates the responsiveness of renal sensory nerves by suppressing
      the PGE2-mediated activation of adenylyl cyclase via a pertussis toxin (PTX)
      sensitive mechanism. In SHR, activation of renal mechanosensory nerves is
      impaired. This is due to suppressed release of substance P in response to
      increased pelvic pressure. The present study was performed to investigate whether
      the PGE2-mediated release of substance P was suppressed in SHR vs. WKY and, if
      so, whether the impaired PGE2-mediated release of substance P was due to ANG II
      activating a PTX-sensitive mechanism. In an isolated renal pelvic wall
      preparation, PGE2, 0.14 microM, increased substance P release from 9 +/- 3 to 22
      +/- 3 pg/min (P < 0.01) in Wistar-Kyoto rats (WKY), but had no effect in
      spontaneously hypertensive rats (SHR). A tenfold higher concentration of PGE2,
      1.4 microM, was required to increase substance P release in SHR, from 7 +/- 1 to
      22 +/- 3 pg/min (P < 0.01). In SHR, treating renal pelvises with losartan
      enhanced the release of substance P produced by subthreshold concentration of
      PGE2, 0.3 microM, from 16 +/- 2 to 26 +/- 3 pg/min (P < 0.01). Likewise, treating
      renal pelvises with PTX enhanced the PGE2-mediated release of substance P from 10
      +/- 1 to 33 +/- 3 pg/min (P < 0.01) in SHR. In WKY, neither losartan nor PTX had
      an effect on the release of substance P produced by subthreshold concentrations
      of PGE2, 0.03 microM. In conclusion, the impaired responsiveness of renal sensory
      nerves in SHR involves endogenous ANG II suppressing the PGE2-mediated release of
      substance P via a PTX-sensitive mechanism.

PMID- 14578116
TI  - Role of EETs in regulation of endothelial permeability in rat lung.
AB  - This study tested the hypothesis that epoxyeicosatrienoic acids (EETs) derived
      from arachidonic acid via P-450 epoxygenases are soluble factors linking
      depletion of endoplasmic reticulum Ca(2+) stores and store-dependent regulation
      of endothelial cell (EC) permeability in rat lung. EC permeability was measured
      via the capillary filtration coefficient (K(f,c)) in isolated, perfused rat
      lungs. 14,15-EET and 5,6-EET increased EC permeability, a response that was
      significantly different from that of 8,9-EET, 11,12-EET, and vehicle control. The
      permeability response to 14,15-EET was not significantly attenuated by the
      nonspecific Ca(2+) channel blocker Gd(3+) (P = 0.068). In lungs perfused with low
      [Ca(2+)], 14,15-EET tended to increase EC permeability, although a significant
      increase in K(f,c) was observed only following Ca(2+) add-back. As positive
      control, we showed that the 3.7-fold increase in K(f,c) evoked by thapsigargin
      (TG), a known activator of store depletion-induced Ca(2+) entry, was blocked by
      both Gd(3+) and low [Ca(2+)] buffer. Nonetheless, the permeability response to TG
      could not be blocked by the phospholipase A(2) inhibitors mepacrine or methyl
      arachidonyl fluorophosphonate or the P-450 epoxygenase inhibitors 17-octadecynoic
      acid or propargyloxyphenyl hexanoic acid. Similarly, combined pretreatment with
      ibuprofen and dicyclohexylurea to block EET metabolism had no effect on the
      permeability response to TG. We conclude that EETs have a heterogeneous impact on
      EC permeability. Despite a requirement for Ca(2+) entry with both TG and 14,15
      EET, our data suggest that distinct signaling pathways or heterogeneity in EC
      responsiveness is responsible for the observed EC injury evoked by EETs and store
      depletion in the isolated rat lung.

PMID- 14578117
TI  - Pepsinogen C: a type 2 cell-specific protease.
AB  - Pepsinogen C, also known as progastricsin or pepsinogen II, is an aspartic
      protease expressed primarily in gastric chief cells. Prior microarray studies of
      an in vitro model of type 2 cell differentiation indicated that pepsinogen C RNA
      was highly induced, comparable to surfactant protein RNA induction. Using second
      trimester human fetal lung, third-trimester postnatal and adult lung, and a model
      of type 2 cell differentiation, we examined the specificity of pepsinogen C
      expression in lung. Pepsinogen C RNA and protein were only detected in >22 wk
      gestation samples of neonatal lung or in adult lung tissue. By
      immunohistochemistry and in situ hybridization, pepsinogen C expression was
      restricted to type 2 cells. Pepsinogen C expression was rapidly induced during
      type 2 cell differentiation and rapidly quenched with dedifferentiation of type 2
      cells after withdrawal of hormones. In all samples, pepsinogen C expression
      occurred concomitantly with or in advance of processing of surfactant protein-B
      to its mature 8-kDa form. Our results indicate that pepsinogen C is a type 2 cell
      specific marker that exhibits tight developmental regulation in vivo during human
      lung development, as well as during in vitro differentiation and
      dedifferentiation of type 2 cells.

PMID- 14578118
TI  - Activation of the anterior cingulate gyrus by 'Green Odor': a positron emission
      tomography study in the monkey.
AB  - The equivalent mixture of cis-3-hexenol and trans-2-hexenal (hexenol/hexenal),
      'green odor', is known to have a healing effect on the psychological damage
      caused by stress. Behavioral studies in humans and monkeys have revealed that
      hexenol/hexenal prevents the prolongation of reaction time caused by fatigue. In
      the present study, we investigated which brain regions are activated by the odor
      of hexenol/hexenal using positron emission tomography with alert monkeys.
      Regional cerebral blood flow (rCBF) in the prepyriform area (the primary
      olfactory cortex) was commonly increased by the passive application of odor:
      acetic acid, isoamylacetate or hexenol/hexenal. We observed rCBF increases in the
      orbitofrontal cortex (the secondary olfactory cortex) by these olfactory stimuli
      in two of three monkeys, and found no predominance of laterality of the activated
      hemisphere. Furthermore, rCBF increase in the cerebellum was observed in two of
      three monkeys, and the odor of acetic acid increased rCBF in the substantia
      innominata in all monkeys. In addition to these olfactory related regions, the
      anterior cingulate gyrus was activated by the odor of hexenol/hexenal. These
      findings suggest that the increase of rCBF in the anterior cingulate gyrus by the
      odor of hexenol/hexenal may contribute the healing effects of this mixture
      observed in the monkey.

PMID- 14578119
TI  - Behavioral evidence for a role of alpha-gustducin in glutamate taste.
AB  - The taste perception of monosodium glutamate (MSG) is termed 'umami'. Two
      putative taste receptors for glutamate have been identified, a truncated form of
      mGluR4 (taste-mGluR4) and the presumed heterodimer T1R1 + T1R3. Both receptors
      respond to glutamate when expressed in heterologous cells, but the G protein
      involved is not known. Galpha-Gustducin mediates the transduction of several
      bitter and sweet compounds; however, its role in umami has not been determined.
      We used standard two-bottle preference tests on alpha-gustducin knockout (KO) and
      wildtype (WT) mice to compare preferences for ascending concentrations of MSG and
      MSG + 5'-inosine monophosphate (IMP). A Latin Square was used to assign the order
      of tastants presented to each mouse. Statistical comparisons between KO and WT
      mice revealed that whereas WT mice preferred solutions of MSG and MSG + IMP over
      water, KO mice showed little preference for these stimuli. Denatonium and sucrose
      served as control stimuli and, as shown previously, WT mice prefered sucrose and
      avoided denatonium significantly more than did KO mice. Naive mice were also
      tested, and while prior exposure to taste stimuli influenced the magnitude of the
      preferences, experience did not change the overall pattern of intake. These data
      suggest that alpha-gustducin plays a role in glutamate taste.

PMID- 14578120
TI  - The septal organ of the rat during postnatal development.
AB  - The septal organ of Masera (SO) is a small, isolated patch of olfactory
      epithelium, located in the ventral part of the nasal septum. We investigated in
      this systematic study the postnatal development of the SO in histological
      sections of rats at various ages from the day of birth (P1) to P666. The SO-area
      increases to a maximum at P66-P105, just as the animals reach sexual maturity,
      and decreases thereafter, significantly however only in males, indicating a
      limited neurogenetic capacity for regeneration. In contrast, the main olfactory
      epithelium area continues to expand beyond P300. The modified respiratory
      epithelium ('zwischen epithelium') separating the SO and the main olfactory
      epithelium contains a few olfactory neurons up to age P66. Its length increases
      postnatally so that the SO becomes more ventral to the OE. Although the position
      of the SO relative to other anatomical landmarks changes with development it is
      consistently located just posterior to the opening of the nasopalatine duct
      (NPAL). Thus, a possible function of the SO is in sensing chemicals in fluids
      entering the mouth by licking and then delivered to the nasal cavity via the
      NPAL; therefore the SO may be involved in social/sexual behavior as is the
      vomeronasal organ (VNO). We suggest that the SO is a separate accessory olfactory
      organ with properties somewhat different from both OE and VNO and may exist only
      in species where the NPAL does not open into the VNO.

PMID- 14578121
TI  - Real-time monitoring of nasal mucosal pH during carbon dioxide stimulation:
      implications for stimulus dynamics.
AB  - Carbon dioxide is a commonly employed irritant test compound in nasal
      chemesthetic studies because it is essentially free of olfactory stimulus
      properties. CO(2) is thought to act via hydration to H(2)CO(3) and dissociation
      to H(+) in nasal mucus, with resulting activation of acid sensors. However,
      transient changes in nasal mucosal pH have not been documented during CO(2)
      stimulation in humans. We placed a small pH probe on the floor of the right
      anterior nasal cavity during CO(2) stimulation in eight human subjects with
      historically high (>30%) and low (< or =20%) CO(2) detection thresholds. Three
      second pulses of CO(2) (15-45% v/v) paired with air in random order (12-15 s
      inter-stimulus interval; 60 s inter-trial interval) were administered by nasal
      cannula at 5 l/min. in an ascending series. For each subject, both a CO(2)
      detection threshold and suprathreshold psychophysical ratings [psi; labeled
      magnitude scale] were generated. All subjects showed phasic drops in pH
      associated with CO(2) stimulation (DeltapH). For all subjects combined, a
      positive correlation was apparent between applied [CO(2)] and both DeltapH and
      psi, as well as between DeltapH and psi themselves (P < 0.0001 for each
      comparison). Subjects with historically low CO(2) thresholds showed steeper dose
      response curves for psi as a function of both applied [CO(2)] and DeltapH, but
      not for DeltapH as a function of applied [CO(2)]. For the six of eight subjects
      with measurable pH changes at threshold, DeltapH was positively related to log
      [CO(2) threshold] (P < 0.01). These data imply that variability in CO(2)
      detection thresholds and suprathreshold rating may derive from intrinsic
      differences in neural sensitivity, rather than differences in stimulus activation
      to hydrogen ion.

PMID- 14578122
TI  - Expression of bHLH transcription factors NSCL1 and NSCL2 in the mouse olfactory
      system.
AB  - We examined the expression of basic helix-loop-helix transcription factors NSCL1
      and NSCL2 in the olfactory epithelium (OE) and the vomeronasal organ (VNO) during
      development. As detected by in situ hybridization, at embryonic day (E) 10 NSCL1
      was weakly expressed in the entire olfactory placodes. From E12 to postnatal day
      (P) 3, NSCL1 was expressed in olfactory receptor neurons (ORNs) and receptor
      neurons of the VNO. The expression pattern of NSCL2 was similar to that of NSCL1.
      By Northern blot analysis, strong expression of NSCL1 was detected in the OE from
      E12 to P7, but the expression there was low in the adult (P35). NSCL2 mRNA was
      detected in the E12 and P1 OE, but its level was very low in the P7 and adult OE.
      The spatial pattern of expression suggests that NSCL1 and NSCL2 contribute to the
      maturation of ORNs (VNO receptor neurons) or maintenance of their differentiated
      state. Moreover, the temporal pattern of expression suggests that NSCL1 and NSCL2
      may function during development rather than in the adult stage.

PMID- 14578123
TI  - Functional characterization of olfactory binding proteins for appeasing compounds
      and molecular cloning in the vomeronasal organ of pre-pubertal pigs.
AB  - The appeasing behaviour of pre-pubertal pigs appears to result from the
      perception of maternal odours (fatty acids) and of steroids coming from the male.
      We have used a ligand-oriented approach to functionally characterize olfactory
      binding proteins involved in the detection of appeasing compounds in the nasal
      mucosa (NM) and the vomeronasal organ (VNO) of pre-pubertal pigs. Several
      proteins were identified, combining binding assay, immunodetection and protein
      sequencing. Their sites of expression in nasal and vomeronasal tissues were
      studied by reverse transcription polymerase chain reaction (RT-PCR). The proteins
      belong to the lipocalin superfamily: Alpha-1-acid glycoprotein (AGP), odorant
      binding protein (OBP), salivary lipocalin (SAL) and Von Ebner's gland protein
      (VEG), and displayed different binding capacities for the appeasing compounds. RT
      PCR experiments showed that OBP and VEG are expressed not only in the NM, but
      also in the VNO and that SAL is only expressed in the VNO. This is the first
      report of the expression of these lipocalins in the VNO. Different binding
      affinities between lipocalins and appeasing compounds, together with their
      different localizations in the olfactory systems, suggest multiple possibilities
      for the peripheral coding of appeasing signals.

PMID- 14578124
TI  - Gene expression for carbonic anhydrase isoenzymes in human nasal mucosa.
AB  - Carbonic anhydrase (CA) is physiologically important in the reversible hydration
      reaction of CO(2); it is expressed in a number of isoforms (CA I-XIV) with
      varying degrees of enzymatic activity. In nasal chemesthesis, CA inhibition
      decreases the electrophysiologic response to CO(2), a common irritant test
      compound. CA enzymatic activity has been demonstrated in the human nasal mucosa
      using enzyme histochemical methods, but no systematic study of nasal mucosal CA
      isoenzyme gene expression has been published. We examined CA gene expression in
      superficial nasal mucosal scrapings from 15 subjects (6 females; 6 allergic
      rhinitics; age range, 21-56 years). Both non-quantitative and quantitative
      reverse transcription polymerase chain reaction (RT-PCR) were performed using
      primers for each gene coding for the 11 catalytically active CA isoenzymes and
      the housekeeping gene GADPH. Amplification products of GADPH and 10 of the 11 CA
      genes were detected in the specimens (CA VA was not detected). Relative
      expression of the CA genes was quantified using real-time PCR. Averaged across
      subjects, the relative abundance of the CA isoenzyme transcripts is as follows:
      CA XII > CA II > CA VB > CA IV > CA IX > CA III > CA XIV > CA I > CA VI > CA VII.
      Limited qualitative validation of gene expression was obtained by
      immunohistochemistry for CA I, CA II and CA IV. We also observed inter-individual
      variability in the expression of CA isoenzymes in human nasal mucosa, potentially
      contributing to differences in nasal chemosensitivity to CO(2) between
      individuals

PMID- 14578125
TI  - Monosodium glutamate and sweet taste: generalization of conditioned taste
      aversion between glutamate and sweet stimuli in rats.
AB  - Even though monosodium glutamate (MSG) is a prototypical umami substance,
      previous studies reported that a conditioned taste aversion (CTA) to MSG, mixed
      with amiloride to block the taste of sodium, generalizes to sucrose. These
      findings suggest that the taste of glutamate mimics the taste of sucrose and
      raise the question of whether glutamate has a broadly tuned sweet taste
      component. To test this hypothesis, CTA experiments were conducted to test for
      generalization between MSG and several sweet stimuli: sucrose, glucose, maltose,
      saccharin and SC-45647. Strong bidirectional generalization was seen between MSG
      mixed with amiloride and sucrose, glucose, saccharin and SC-45647. Weak
      generalization was seen between MSG and maltose, and sucrose and maltose. None of
      the CTAs generalized to NMDA. These findings support the hypothesis that the
      taste of MSG has broadly tuned, sweet-like characteristics, possibly due to the
      convergence of afferent signals for MSG, natural sugars and artificial
      sweeteners.

PMID- 14578126
TI  - Individual differences in sensitivity to the odor of 4,16-androstadien-3-one.
AB  - Individual differences in sensitivity to the putative human pheromone
      androstadienone were investigated in three experiments. In experiment 1, the
      absolute detection threshold for androstadienone was determined to be 211 micro M
      using the method of constant stimuli. Detection for the related compound
      estratetraenol was also investigated but a threshold could not be determined. In
      experiment 2, using an adaptive threshold test on 100 participants, the
      sensitivity distribution for androstadienone, but not for the reference odor
      phenylethyl alcohol, was bimodal, with a smaller group of individuals with a high
      sensitivity to androstadienone (supersmellers). A lack of correlation between
      thresholds for androstadienone and phenylethyl alcohol further suggested that the
      bimodality for androstadienone was not due to individuals with a high general
      olfactory sensitivity. In line with an earlier observation, there was a
      statistical tendency for women to be more sensitive to androstadienone than men.
      Results of experiment 3 preclude the possibility that the bimodal sensitivity
      distribution for androstadienone would depend on individual differences in
      trigeminal activation. Altogether, the current study suggests that olfactory
      sensitivity to androstadienone is bimodally distributed in the population with a
      subgroup consisting of highly sensitive people.

PMID- 14578127
TI  - Olfactory metacognition.
AB  - The current paper focuses on the subjective knowledge people have about their
      ability to name odors. Previous investigations of such metacognitive aspects of
      olfactory cognition are very scarce and have yielded results that need further
      scrutiny. In two experiments, we investigated three metamemory judgments about
      odor identity. As opposed to previous findings, participants' feeling of knowing
      judgments about odor identity predicted later recognition. Participants were also
      accurate but highly overconfident in their retrospective confidence in odor
      identification. A strong and imminent feeling of being able to name an odor, a so
      called 'tip of the nose' experience, was found to predict later recall, but was
      otherwise poorly related to any partial activation of the odor name or other
      information associated with the odor. This makes it different from the commonly
      investigated 'tip of the tongue' phenomenon. The current study shows that
      olfactory metamemory is related to actual knowledge, a finding that is in line
      with what has been observed for other modalities.

PMID- 14578128
TI  - Relationship between mechanisms, bioavailibility, and preclinical chemopreventive
      efficacy of resveratrol: a conundrum.

PMID- 14578129
TI  - Polymorphism in the thymidylate synthase promoter enhancer region modifies the
      risk and survival of colorectal cancer.
AB  - Thymidylate synthase (TS) converts dUMP to dTMP, the rate-limiting nucleotide in
      DNA synthesis. It is also the target for 5-flurorouracil, the most common
      chemotherapy agent for treatment of colorectal cancer (CRC). We designed a nested
      case-control study within the prospective Physicians' Health Study to investigate
      whether TS polymorphisms independently predict risk of CRC and simultaneously the
      overall survival after the disease in the same population. We also investigated
      influences of this polymorphism on plasma folate and homocysteine levels. The
      study consists of 270 incident CRC and 454 control subjects. Risk of CRC was
      estimated by use of conditional multiple logistic regression analysis. Survival
      was analyzed by Cox proportional hazards regression analysis. Compared with the
      TS 3R/3R genotype, the multivariate-adjusted risk ratio was 0.86 (0.59-1.25) for
      the 2R/3R genotype and 0.59 (0.36-0.98) for the 2R/2R genotype with P for trend
      of 0.03. The TS 2R/2R genotype was also associated with better survival, although
      the results were not significant. Compared with those with either the 3R/3R or
      2R/3R genotypes, the age-adjusted hazard ratio for the 2R/2R genotype was 0.57
      (0.30-1.07). Individuals with the 2R/2R genotype had significantly lower plasma
      folate levels than those with the 3R/3R genotype, whereas their plasma
      homocysteine levels were unaffected by the TS promoter polymorphism. The deletion
      polymorphism at the TS 3'-untranslated region did not influence the CRC risk and
      survival, nor did it modify the plasma folate and total homocysteine levels.
      Given that individuals with high plasma folate had a better survival outcome with
      a hazard ratio of 0.68 (0.45-1.03) compared with those with low plasma folate, we
      conclude that the TS promoter polymorphism may modify both the risk and the
      survival of CRC; however, these effects do not appear to be mediated through its
      modulation of biological folate levels.

PMID- 14578130
TI  - Association between low dietary folate intake and suboptimal cellular DNA repair
      capacity.
AB  - Both reduced DNA repair capacity (DRC) and folate deficiency are associated with
      increased cancer risk. Furthermore, folate is involved in DNA repair through de
      novo DNA synthesis and methylation. To determine whether low dietary folate
      intake is associated with low cellular DRC in humans, we assessed total dietary
      folate intake using a food frequency questionnaire in 559 non-Hispanic white
      cancer-free subjects enrolled from 1995 through 2001 as controls for ongoing
      molecular epidemiological studies from among enrollees in a community-based
      multispecialty physician practice in the Houston metropolitan area. We assessed
      cellular DRC using the host-cell reactivation assay that measures nucleotide
      excision repair capacity in peripheral blood lymphocytes. The distribution of DRC
      was approximately normal in this study population. In univariate analysis,
      subjects in the lowest tertile of total dietary folate intake (<170 microg/1000
      kcal/day) exhibited a significant reduction (-18%) in DRC compared with those in
      the upper tertile (>225 microg/1000 kcal/day; P < 0.001). In multivariate linear
      regression analysis, calorie-adjusted total folate intake remained an independent
      predictor of DRC (P < 0.001). Additional stratification analysis indicated that
      this association was more pronounced in those who did not use folate
      supplementation (n = 230; P < 0.001) compared with those who did (n = 329; P =
      0.177). Our findings suggest that low dietary folate intake is associated with
      suboptimal cellular DRC. Once replicated by other investigators, this finding has
      public health implications by reinforcing the need for folate supplementation or
      dietary modification for the at-risk population.

PMID- 14578131
TI  - Methylenetetrahydrofolate reductase, alcohol dehydrogenase, diet, and risk of
      colorectal adenomas.
AB  - An increased occurrence of colorectal cancer and its adenoma precursor is
      observed among individuals with low intakes or circulating levels of folate,
      especially if alcohol intake is high, although results have not been
      statistically significant in all studies. We examined folate and alcohol intake
      and genetic polymorphisms in methylenetetrahydrofolate reductase [MTHFR 667-->T
      (ala-->val) and MTHFR 1298A-->C (gln-->ala)] (associated with reduced MTHFR
      activity) and in alcohol dehydrogenase 3 [ADH3 (2-2) associated with decreased
      alcohol catabolism] in relation to risk of colorectal adenoma in the Health
      Professionals Follow-Up Study. Among 379 cases and 726 controls, MTHFR genotypes
      were not appreciably related to risk of adenoma, but a suggestive interaction (P
      = 0.09) was observed between MTHFR 677C-->T and alcohol intake; men with TT
      homozygotes who consumed 30+ g/day of alcohol had an odds ratio (OR) of 3.52 [95%
      confidence interval (CI), 1.41-8.78] relative to drinkers of < or =5 g/day with
      the CC/CT genotypes. ADH3 genotype alone was not appreciably related to risk, but
      its influence was modified by alcohol intake. Compared with fast alcohol
      catabolizers [ADH3(1-1)] with low intakes of alcohol (< or =5 g/day), high
      consumers of alcohol (30+ g/day) had a marked increase in risk if they had the
      genotype associated with slow catabolism [ADH3(2-2); OR, 2.94; 95% CI, 1.24-6.92]
      or intermediate catabolism [ADH3(1-2)] of alcohol (OR, 1.83; 95% CI, 1.03-3.26)
      but not if they were fast catabolizers [ADH3(1-1); OR = 1.27; 95% CI = 0.63
      2.53). In addition, an increased risk of colorectal adenoma (OR, 17.1; 95% CI,
      2.1-137) was observed for those with the ADH3(2-2) genotype and high alcohol-low
      folate intake compared with those with low alcohol-high folate intake and the
      ADH3(1-1) genotype (P for interaction = 0.006). Our results indicate that high
      intake of alcohol is associated with an increased risk of colorectal adenoma,
      particularly among MTHFR 677TT and ADH3(2-2) homozygotes. The findings that
      alcohol interacts with a folate-related gene (MTHFR) and that the interaction
      between alcohol and ADH3 is stronger among those with low folate intake support
      the hypothesis that the carcinogenic influence of alcohol in the large bowel is
      mediated through folate status.

PMID- 14578132
TI  - Dietary folate intake and lung cancer risk in former smokers: a case-control
      analysis.
AB  - No studies have focused on the role of dietary folate intake in risk of lung
      cancer in former smokers, in whom dietary folate intake is less likely confounded
      with current smoking. Therefore, we evaluated the association between dietary
      folate intake and risk of lung cancer in a population of 470 histopathologically
      confirmed incident lung cancer cases from M. D. Anderson Cancer Center and 472
      cancer-free controls from enrollees at a community-based multispecialty physician
      practice, frequency-matched on age (5 years), sex, and ethnicity. Dietary folate
      intake levels were estimated from a National Cancer Institute standard food
      frequency questionnaire. Unconditional logistic regression analyses were used to
      calculate the crude and adjusted ORs and their 95% CIs. Dietary folate intake
      from natural food was significantly higher among the controls than among the
      cases (P < 0.001), and folate intake above the control median value was
      associated with a 40% decreased risk of lung cancer (adjusted OR, 0.60; 95% CI,
      0.45-0.79). A significant inverse dose-response relationship between increasing
      dietary folate and decreasing risk of lung cancer was also evident (adjusted OR,
      1.02; 95% CI, 0.71-1.47; OR, 0.67; 95% CI, 0.46-0.99; and OR, 0.53; 95% CI, 0.35
      0.80 for the second, third, and fourth quartiles of average folate intake,
      respectively; P for trend <0.001). A more pronounced inverse association between
      dietary folate intake and lung cancer risk was observed among subjects who drank
      alcohol, had smoked relatively more, those who did not take supplemental folate,
      and those who reported a family history of lung cancer. Our data suggest that
      there is a possible protective role of dietary folate in lung carcinogenesis, a
      finding which may have implications in public health and cancer prevention.

PMID- 14578133
TI  - Sputum cytological atypia as a predictor of incident lung cancer in a cohort of
      heavy smokers with airflow obstruction.
AB  - Individuals with cytological atypia in sputum may be at increased risk for lung
      cancer. We conducted a longitudinal analysis of the association between lung
      cancer incidence and cytological atypia in sputum samples collected prospectively
      from an ongoing cohort of adults at high risk for lung cancer. Cohort members had
      a smoking history of > or = 30 pack-years and chronic obstructive pulmonary
      disease documented by pulmonary airflow testing. Sputum samples collected at
      baseline and periodically thereafter were examined by standard cytological
      methods. From the cohort of 2,006 people, there were 83 incident lung cancers
      over 4,469 person-years of observation. At baseline, the association between
      personal and behavioral characteristics, and sputum cytological atypia was
      assessed by multiple logistic regression. The association between sputum
      cytological atypia and incident lung cancer was then assessed by hazard ratios
      using proportional hazards regression analysis, adjusting for potential
      confounding factors. Cytological atypia graded as moderate or worse was
      associated with continuing cigarette smoking (adjusted odds ratio, 2.5; 95%
      confidence interval, 1.5-4.1), and with lower levels of intake of fruits and
      vegetables (P for trend = 0.04). Atypia was not associated with several other
      factors, including the degree of airflow obstruction, the use of vitamin
      supplements, nonsteroidal anti-inflammatory drugs, or metered-dose steroid
      inhalers. Incident lung cancer was increased among those with moderate or worse
      cytological atypia (adjusted hazards ratio, 2.8; 95% confidence interval, 1.4
      5.5). This association was not confounded by other risk factors. We conclude that
      in this high-risk cohort, cytological atypia is associated with continuing
      smoking and low intake of fruits and vegetables, but that independent of these
      and other factors, the risk of incident lung cancer is increased among those with
      moderate or worse grades of cytological atypia in their sputum.

PMID- 14578136
TI  - The I1307K adenomatous polyposis coli gene variant does not contribute in the
      assessment of the risk for colorectal cancer in Ashkenazi Jews.
AB  - Ashkenazi Jews with the I1307K adenomatous polyposis coli gene variant were
      suggested to confer a higher risk for colorectal cancer (CRC). We assessed the
      clinical importance of this polymorphism in Israeli Jews at average and elevated
      risk for CRC. Among 1,370 consecutive subjects that were examined, 975 Ashkenazi
      Jews were stratified into those at average risk (no personal or family history of
      colorectal neoplasia) and those at high risk. DNA was obtained from peripheral
      leukocytes and amplified by PCR, with primers designed to detect the I1307K
      variant. Overall, I1307K polymorphism was found in 7.1% (9.1% among Ashkenazi and
      1.7% among non-Ashkenazi Jews). The carrier rate was 8.3 and 9.3% in average and
      high-risk Ashkenazim, respectively (P = 0.65). The overall odds ratio for
      neoplasia in carriers was 1.43 (95% confidence interval, 0.89-2.30). Age, gender,
      and the histopathological features of adenomas and cancers did not differ between
      carriers and noncarriers. No interaction on the CRC risk was found between I1307K
      variant and lifestyle modifiers (such as cigarette smoking, alcohol consumption,
      high body mass index, low physical activity, and vitamins/antioxidant intake).
      The I1307K adenomatous polyposis coli gene variant is not an important marker for
      increased risk for CRC. It confirms previous reports of a slight nonsignificant
      increase (OR, 1.4) in the risk of CRC in these carriers. There is no interaction
      effect on the risk of colorectal neoplasia between the I1307K variant and various
      lifestyle risk factors. The usual recommended screening and surveillance
      strategies should be used for carriers of this polymorphism.

PMID- 14578135
TI  - Smoking exposure as a risk factor for prevalent and recurrent colorectal
      adenomas.
AB  - Colorectal adenomatous polyps are considered to be the precursor lesion of
      colorectal cancer (1-3). Greater understanding of the association between smoking
      and adenoma development enable better detection and prevention of colorectal
      cancer. This study was conducted in men and women, ages 40-80, participating in a
      randomized trial testing the effects of wheat bran fiber supplement on adenoma
      recurrence. First, we investigated smoking exposure (status, cigarettes/day, and
      years of smoking) and colorectal adenoma characteristics (location, histology,
      size, and multiplicity) at baseline colonoscopy (n = 1429). Second, we evaluated
      smoking exposure and adenoma recurrence (n = 1304). The prevalence of distal
      versus proximal adenomas was greater for < or =30 cigarettes/day [odds ratio
      (OR), 1.48; 95% CI, 1.02-2.16] and 15 to <25 years of smoking (OR, 1.95; 95% CI,
      1.23-3.09) compared with never smokers. Tubular versus villous histology
      prevalence was increased for > or =30 cigarettes and > or =35 years of smoking
      (OR, 1.74; 95% CI, 1.21-2.49 and OR, 1.74; 95% CI, 1.24-2.45, respectively)
      compared with never-smokers. Years of smoking increased prevalence of multiple
      versus single adenomas, whereas cigarettes/day and years of smoking were
      associated with large adenomas (> or =1 cm) prevalence as compared with small
      lesions (< or =0.5 cm). Greater than 35 years of smoking was significantly
      associated with an increased risk of adenoma recurrence (OR, 1.42; 95% CI, 1.01
      1.98). These results suggest that the association between smoking and adenoma
      prevalence varies by the characteristic of the lesion. Furthermore, the
      association between smoking and adenoma recurrence is modest and was only
      significant after a long duration of exposure. Additional investigations that
      characterize the genetic changes in specific subgroups of prevalent and recurrent
      adenomas associated with smoking exposure are needed.

PMID- 14578137
TI  - No effect of 600 grams fruit and vegetables per day on oxidative DNA damage and
      repair in healthy nonsmokers.
AB  - In several epidemiological studies, high intakes of fruits and vegetables have
      been associated with a lower incidence of cancer. Theoretically, intake of
      antioxidants by consumption of fruits and vegetables should protect against
      reactive oxygen species and decrease the formation of oxidative DNA damage. We
      set up a parallel 24-day dietary placebo-controlled intervention study in which
      43 subjects were randomized into three groups receiving an antioxidant-free basal
      diet and 600 g of fruits and vegetables, or a supplement containing the
      corresponding amounts of vitamins and minerals, or placebo. Blood and urine
      samples were collected before, once a week, and 4 weeks after the intervention
      period. The level of strand breaks, endonuclease III sites, formamidopyrimidine
      sites, and sensitivity to hydrogen peroxide was assessed in mononuclear blood
      cells by the comet assay. Excretion of 7-hydro-8-oxo-2'-deoxyguanine was measured
      in urine. The expressions of oxoguanine glycosylase 1 and excision repair cross
      complementing 1 DNA repair genes, determined by real-time reverse transcription
      PCR of mRNAs, were investigated in leukocytes. Consumption of fruits and
      vegetables or vitamins and minerals had no effect on oxidative DNA damage
      measured in mononuclear cell DNA or urine. Hydrogen peroxide sensitivity,
      detected by the comet assay, did not differ between the groups. Expression of
      excision repair cross complementing 1 and oxoguanine glycosylase 1 in leukocytes
      was not related to the diet consumed. Our results show that after 24 days of
      complete depletion of fruits and vegetables, or daily ingestion of 600 g of fruit
      and vegetables, or the corresponding amount of vitamins and minerals, the level
      of oxidative DNA damage was unchanged. This suggests that the inherent
      antioxidant defense mechanisms are sufficient to protect circulating mononuclear
      blood cells from reactive oxygen species.

PMID- 14578134
TI  - Environmental and genetic determinants of tobacco use: methodology for a
      multidisciplinary, longitudinal family-based investigation.
AB  - This article describes the ongoing collaborative effort of six research teams to
      operationalize and execute an integrative approach to the study of gene x
      environment interactions in the development of tobacco dependence. At the core of
      the project is a longitudinal investigation of social and behavioral risk factors
      for tobacco use in individuals who were, on average, 13 years of age at intake
      and for whom smoking outcomes extending from early adolescence to young adulthood
      have been characterized previously (current average age of the cohort is 29
      years). The conceptual framework for the integrative approach and the
      longitudinal investigation on which the study is based is presented. A
      description is also provided of the methods used to: (a) recruit participants and
      families to provide DNA samples and information on tobacco use; (b) assess
      participants for relevant tobacco-related phenotypes including smoking history,
      current use of tobacco, and nicotine metabolism; (c) assess the quality of the
      DNA samples collected from participants for genome-wide scanning and candidate
      gene analysis; (d) examine several research questions concerning the role of
      genetic and environmental factors in the onset and maintenance of tobacco use;
      and (e) ensure adherence to local and federal guidelines for ethical and legal
      investigations of genotypic associations with tobacco-related phenotypes in
      families. This investigation is unique among ongoing studies of the genetics of
      tobacco dependence in the extent to which equal importance has been assigned to
      both phenotypic and genotypic measurements.

PMID- 14578138
TI  - The APC E1317Q variant in adenomatous polyps and colorectal cancers.
AB  - Genetic susceptibility may play a role in many colorectal cancers (CRCs). Known
      syndromes such as familial adenomatous polyposis and hereditary nonpolyposis CRC
      account for <5% of CRCs. The germ-line missense variant of the APC gene, E1317Q,
      has been proposed to confer a risk for colonic adenomatous polyps (adenomas), but
      not for CRCs in the general population. These findings are contradictory and
      controversial. In the present study, 608 cases (377 patients with CRC, 145
      patients with 4-100 lifetime adenomas, and 86 with < or =3 lifetime adenomas),
      and 679 controls (362 spouses and 317 patients with normal colonoscopy) were
      screened for the APC E1317Q variant. The frequency of heterozygotes for E1317Q
      among patients with CRC (2.4%), patients with 4-100 adenomas (1.4%), and < or =3
      adenomas (3.5%) did not differ from spouse controls (2.8%). When CRC patients
      were examined by DNA mismatch repair status, age at onset (< or =age 50 versus
      >50), or family history of CRC, no differences in the frequency of E1317Q were
      found. The APC variant E1317Q does not appear to be associated with increased
      risk for colorectal neoplasia in the general population. However, when we used
      normal colonoscopy controls (E1317Q carrier frequency = 0.3%), the prevalence of
      E1317Q was significantly increased in CRC patients, in patients with < or =3
      adenomas, and in CRC patients with intact mismatch repair status, suggesting a
      possible role for E1317Q in colorectal tumorigenesis. These results underscore
      the importance of carefully defining the controls to be used in comparisons of
      allele frequencies.

PMID- 14578139
TI  - Predictors of cervical coinfection with multiple human papillomavirus types.
AB  - Women infected with multiple human papillomavirus (HPV) types seem to be at
      higher risk of cervical intraepithelial neoplasia, although there is controversy
      about whether coinfections are associated with lower or higher grades of
      dysplasia. There is no established risk factor profile for infection with
      multiple HPV types. We analyzed data from a prospective cohort of 2,075 Brazilian
      women to identify determinants of HPV coinfection. Cervical specimens were
      collected for cytology and HPV DNA detection. Data on baseline and time-dependent
      putative risk factors were obtained by interview. Baseline predictors of HPV
      coinfection included younger age, greater number of recent sexual partners, a
      history of condyloma but not of other sexually transmitted diseases, and younger
      age at first sexual intercourse. In repeated measures analyses, there was a weak
      positive association between the number of sexual partners in the time interval
      between two study visits and the risk of coinfection. Our results suggest that
      the risk factor profile for HPV coinfection among HPV-infected women shares
      several similarities with risk factors for any HPV infection.

PMID- 14578140
TI  - Determinants of human papillomavirus load among women with histological cervical
      intraepithelial neoplasia 3: dominant impact of surrounding low-grade lesions.
AB  - Measurement of human papillomavirus (HPV) DNA load has been suggested as a means
      for improving the positive predictive value of HPV testing for detecting cervical
      intraepithelial neoplasia 3 and cancer (CIN3+). We hypothesized that lesions
      surrounding CIN3+ (especially the extent of associated CIN1) are important
      determinants of load, which limit its clinical use. To test this hypothesis, we
      reviewed the pathology of women at enrollment in the Atypical Squamous Cells of
      Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study
      who were managed at enrollment with oncogenic HPV testing using Hybrid Capture 2
      (Digene Corp., Gaithersburg, MD) or colposcopy. We focused our analysis on 133
      cases of CIN3+ that were identified, stratified by the number of HPV types
      detected using a PCR-based method (62 single, 71 multiple infections). Infection
      with multiple types (P < 0.01) and identification of CIN1 or CIN2 in tissues
      surrounding CIN3 (P = 0.01) were each significantly associated with higher load
      (two-way ANOVA). Higher load was associated with more extensive CIN1 (P < 0.01),
      especially when associated with multiple HPV types. Intensive partial rescreening
      of enrollment thin-layer slides obtained from women with histopathological CIN3+
      revealed that ASC-US/LSIL cells were more numerous than ASC-H/HSIL cells. ASC
      US/LSIL cell counts were significantly correlated with load (r = 0.31; P < 0.01),
      whereas counts of ASC-H/HSIL cells were uncorrelated. We conclude that the extent
      of histopathological CIN1, number of HPV types, and the number of ASC-US/LSIL
      cells in exfoliative cervical samples vary greatly among cases of CIN3+ and
      strongly affect HPV load. These factors severely limit the clinical use of load
      measurements irrespective of HPV testing methodology.

PMID- 14578141
TI  - Segregation analysis of 231 Ashkenazi Jewish families for evidence of additional
      breast cancer susceptibility genes.
AB  - Between 5 and 10% of breast cancer is attributable to inherited cancer
      susceptibility genes. Mutations in the genes BRCA1 and BRCA2 account for two
      thirds of hereditary breast cancer cases. Using segregation analysis, families of
      cases without BRCA1/2 mutations were studied for statistical evidence of another
      major breast cancer gene in a community-based sample of Jewish probands tested
      previously for the presence of three BRCA founder mutations. A total of 231
      probands with breast cancer, who do not carry a founder mutation, reported
      complete data on 602 female first-degree relatives of probands over age 20; 78 of
      these relatives had breast cancer. Segregation analysis was used to evaluate the
      likelihood of various genetic and nongenetic models. Sporadic, environmental, and
      general Mendelian genetic models fit the family data poorly and were rejected. A
      Mendelian recessive model fit better than dominant and codominant models,
      although none of these could be rejected. Cumulative incidence curves predicted
      by the recessive and codominant models fit observed incidence among first-degree
      relatives well. The assumption of Mendelian transmission of a major recessive
      gene(s) is compatible with the data. The recessive model predicts that 4% of
      women would carry the high-risk genotype, with 85% of them developing breast
      cancer by age 70. There was significant heterogeneity between these families and
      the 114 BRCA1/2 mutation-positive families from the same study population,
      implying that this apparent recessive effect is not because of undetected BRCA1/2
      mutations. The study adds support for a major autosomal recessive component to
      breast cancer susceptibility.

PMID- 14578142
TI  - Hormonal factors and the risk of breast cancer according to estrogen- and
      progesterone-receptor subgroup.
AB  - Evidence suggests hormonal factors may be more strongly associated with estrogen
      receptor+progesterone receptor+ (ER+PR+) than ER-PR- breast cancer risk. This
      study evaluated risk factors according to ERPR tumor status among pre- and
      postmenopausal women participating in two recent population-based case-control
      studies. Breast cancer cases, ages 25-74 years, and diagnosed 1995-1998 were
      sampled from the Ontario Cancer Registry. Controls were a random sample of women
      identified using the Ontario Ministry of Finance rolls and were frequency-matched
      to cases within 5-year age groups. Epidemiological data were collected from
      breast cancer cases and controls using two self-administered questionnaires. ERPR
      data were obtained for 87% of the breast cancer cases (3,276 of 3,748).
      Multivariate polytomous logistic regression was used to obtain odds ratios
      estimates and 95% confidence intervals. The following significant differences
      were observed in the risk factor profiles for ER+PR+ and ER-PR- breast cancer:
      among premenopausal women, late age at menarche was only associated with a
      reduction in ER+PR+ breast cancer risk; obesity was associated with an increased
      ER-PR- and decreased ER+PR+ cancer risk; and the association between alcohol
      intake and breast cancer risk was heterogeneous across ERPR subgroups, although
      the direction varied across the levels of alcohol intake. Among postmenopausal
      women, there were no statistically significant differences observed in the risk
      factor profiles for ER+PR+ and ER-PR- breast cancer. Some heterogeneity exists in
      the risk factor profiles of ER+PR+ and ER-PR- premenopausal breast cancer;
      however, risk factor profiles did not differ markedly for postmenopausal breast
      cancer.

PMID- 14578143
TI  - The relationship between alcohol use and risk of breast cancer by histology and
      hormone receptor status among women 65-79 years of age.
AB  - Alcohol consumption is associated with a moderate increase in breast cancer risk,
      possibly because alcohol increases estrogen levels in blood. Certain types of
      breast carcinomas are more hormonally responsive than others, including those
      that have a lobular histology or are hormone receptor positive, but few studies
      evaluating alcohol use and breast cancer risk have stratified results by
      histology or estrogen receptor (ER)/progesterone receptor (PR) status. We
      conducted a population-based case-control study of women 65-79 years of age in
      western Washington State. Women (975) diagnosed with invasive breast cancer
      during 1997-1999 were compared with 1007 controls. Ever-use of alcohol over the
      past 20 years was associated with a 1.3-fold [95% confidence interval (CI), 1.0
      1.5] increased risk of breast cancer, although this increase was primarily
      limited to women who consumed > or =30.0 g/day of alcohol [odds ratio (OR), 1.7;
      95% CI, 1.1-2.6]. Differences in risk by histology were observed: ever-use of
      alcohol was associated with a 1.8-fold (95% CI, 1.3-2.5) increased risk of
      lobular cancer but only a 1.2-fold (95% CI, 0.9-1.4) increased risk of ductal
      cancer. Ever-users of alcohol had an increase in risk of ER+/PR+ tumors (OR, 1.3;
      95% CI, 1.1-1.7), but no change in their risks of ER+/PR- or ER-/PR- tumors.
      Alcohol use appears to be more strongly associated with risk of lobular
      carcinomas and hormone receptor-positive tumors than it is with other types of
      breast cancer. These results are consistent with there being an underlying
      hormonal basis for the known association between alcohol use and breast cancer
      incidence.

PMID- 14578144
TI  - Joint effect of insulin-like growth factors and sex steroids on breast cancer
      risk.
AB  - Insulin-like growth factors (IGFs) and estrogens are essential hormones
      regulating the growth and differentiation of mammary cells. Studies have shown
      that IGFs and estrogens are strong mitogens for breast cancer cells and that high
      circulating IGF-I and estrogens are risk factors of breast cancer. Laboratory
      experiments further indicate that these hormones act synergistically on the
      pathogenesis of breast cancer. Estrogens increase the effect of IGF-I on breast
      cancer cells by stimulating the expression of IGF-I and IGF-I receptor; IGFs
      enhance the action of estrogens by regulating the production of estrogen
      receptor. Furthermore, the two systems have substantial signal transduction cross
      talk. Despite the laboratory indications, there is no epidemiological evidence in
      support of the joint effect of IGFs and estrogens on breast cancer risk. To test
      this hypothesis in human populations, we compared plasma levels of IGFs and sex
      steroid hormones among 300 incident breast cancer patients and 300 age- and
      menopause-matched control women derived from a large population-based case
      control study conducted in Shanghai, China between 1996 and 1998. Fasting morning
      blood samples were measured for plasma concentrations of IGF-I, IGF-II, IGF
      binding protein (IGFBP)-3, estradiol, estrone, estrone sulfate, testosterone, and
      dehydroepiandrosterone sulfate using commercial immunoassay kits. Levels of these
      hormones were classified into two groups based on the median levels in the
      control group and combined between IGFs and steroid hormones. Conditional
      logistic regression analysis was performed to examine the association of breast
      cancer risk with the combined variables of sex steroids and IGFs. A synergistic
      effect on breast cancer risk was suggested for IGF-I or IGFBP-3 with estrone or
      testosterone among both pre- and postmenopausal women. Compared with
      premenopausal women with low circulating levels of both IGF-I and estrone, the
      odds ratios were 1.21 [95% confidence interval (CI), 0.61-2.40] for high estrone,
      1.50 (95% CI, 0.77-2.93) for high IGF-I, and 2.30 (95% CI, 1.21-4.37) for both
      high estrone and high IGF-I. Similar patterns of association were also seen for
      IGF-I with testosterone as well as for IGFBP-3 with estrone or testosterone, and
      some of the interactions were statistically significant or borderline significant
      (P < 0.10). No joint effects were found for IGF-I or IGFBP-3 with estradiol or
      estrone sulfate. In conclusion, the study suggests a possible synergy between IGF
      peptide hormone and sex steroid hormones, including both estrogen and androgen,
      in relation to breast cancer risk.

PMID- 14578145
TI  - Associations of breast cancer risk factors with breast density in Hispanic women.
AB  - Although there has been much research on the factors associated with breast
      density, most studies did not include Hispanic women or relied on
      semiquantitative methods of assessing density. Using data from the Chicago Breast
      Health Project, which targeted Hispanic women and assessed density quantitatively
      using full-field digital mammography, we assessed cross-sectional associations of
      breast cancer risk factors with percentage of breast density. Between November
      2000 and June 2002, 296 Hispanic women recruited from three community health
      centers in Chicago, Illinois completed a health and lifestyle questionnaire, had
      their height and weight measured, and underwent screening mammography. The
      average percentage of total breast area occupied by fibroglandular tissue was
      computed from each mammographic view. Associations of breast cancer risk factors
      with percentage of breast density were assessed using multivariate linear
      regression analyses. Overall, the mean percentage of breast density was 17.6%. In
      multivariate analysis, older age was associated with lower density (P = 0.03),
      and density was lower among postmenopausal than premenopausal women (beta = 5.2%;
      P = 0.002). Body mass index was significantly inversely related to percentage of
      breast density (P < 0.00001). Women currently taking hormone replacement therapy
      had a higher percentage of breast density (beta = 3.3%; P = 0.03). In
      premenopausal women, cigarette smokers had a marginally higher percentage of
      density (beta = 6.23%; P = 0.06) compared with nonsmokers, but there was no
      relationship for postmenopausal women. Other breast cancer risk factors were not
      associated with density. In summary, breast density was strongly and inversely
      associated with age, body mass index, and menopausal status, and positively
      associated with hormone replacement therapy use and cigarette smoking. Additional
      research focusing on relationships of other, potentially modifiable, factors with
      the extent of breast density is warranted to better understand the
      interindividual variability in density among Hispanic women.

PMID- 14578146
TI  - Relationship of mammographic parenchymal patterns to breast cancer risk factors
      and smoking in Alaska Native women.
AB  - The purpose is to determine breast cancer risk factors and correlates of
      mammographic parenchymal patterns among Alaska Native women. A retrospective
      review was performed of mammograms and mammogram records among 528 sequential
      screening mammogram examinations performed in Anchorage, Alaska. Mammogram
      density was classified by American College of Radiology (Breast Imaging Reporting
      and Data System) density patterns 1-4 (fat-->dense) and by percent density.
      Clinical data, including risk factors, ethnic group (Indian, Aleut, or Eskimo),
      and smoking status were obtained. Results were analyzed by univariate and
      multivariate analyses. Of 528 women, 164 were Indian, 155 were Aleut, and 209
      were Eskimo. Mean age at first birth was lower and parity higher compared with
      published data in white women. Breast cancer risk factors were similar across
      ethnic groups. In multivariate analysis, patient age, parity, hormone replacement
      therapy, hysterectomy, and history of biopsy were associated, and smoking was not
      associated with density scores. Aleut and Indian women were less likely to have
      high-density mammograms than were Eskimo women (P = 0.0448). No significant
      differences were found between ethnic group for conventional breast cancer risk
      factors. Mammogram density was associated with age at screening, parity, hormone
      replacement therapy, hysterectomy, history of biopsy, and ethnicity but not
      smoking status. Eskimo women had higher mammogram density than Aleuts or Indians.

PMID- 14578147
TI  - Recruitment and retention challenges in breast cancer survivorship research:
      results from a multisite, randomized intervention trial in women with early stage
      breast cancer.
AB  - The Moving Beyond Cancer trial is a multisite randomized, controlled trial of an
      individualized psychoeducational intervention for women with early stage breast
      cancer. Recruitment early in the cancer trajectory and assessment of retention at
      multiple points are notable features of the research, offering a unique
      opportunity to examine recruitment, retention, and predictors of participation.
      Patients were registered for the study within 6 weeks after definitive surgery
      and followed until primary medical treatment completion, whereupon they were
      enrolled, administered baseline measures, and randomized to one of three arms. Of
      2,242 women referred, 41% were ineligible. Of eligible women, 42% elected
      participation through the point of randomization (n = 558). Participants did not
      differ from nonparticipants on initial self-reported physical functioning and
      mental health status, employment status, cancer history, cancer treatment plan,
      or previous cancer-related research participation. Women who were over 65 years
      of age, of racial minority status, unmarried, or less educated were less likely
      to participate through the point of randomization. Thus, several patient
      characteristics predicted trial participation, indicating the need for targeted
      recruitment attempts.

PMID- 14578148
TI  - Influence of the Mediterranean diet on the risk of cancers of the upper
      aerodigestive tract.
AB  - The hypothesis that the Mediterranean diet has a beneficial role on the risk of
      cancers of the upper aerodigestive tract has been evaluated using data from three
      case-control studies conducted in Italy between 1992 and 2000. The first study
      included 598 cases with incident, histologically confirmed cancers of the oral
      cavity and pharynx and 1491 hospital controls admitted to the same network of
      hospitals as cases for acute, nonneoplastic diseases. The second one included 304
      subjects with squamous cell carcinoma of the esophagus and 743 controls. The
      third one included 460 laryngeal cancer cases and 1088 controls. A score
      summarizing eight of the major characteristics of the Mediterranean diet was
      used. Odds ratios and corresponding 95% confidence intervals (CIs) for increasing
      levels of this score were estimated using unconditional regression models,
      adjusted for age, sex, study center, years of education, tobacco consumption,
      body mass index, and total energy intake. For all cancers considered, a reduced
      risk was found for increasing levels of the Mediterranean score: the odds ratios
      for subjects with six or more Mediterranean characteristics, compared with those
      with less than three characteristics, were 0.40 (95% CI, 0.26-0.62) for oral and
      pharyngeal, 0.26 (95% CI, 0.13-0.51) for esophageal, and 0.23 (95% CI, 0.13-0.40)
      for laryngeal cancer. All of the estimates were consistent in strata of the major
      identified risk factors for these neoplasms. This study provides evidence that an
      a priori defined nutritional pattern, which includes several aspects of the
      Mediterranean diet, favorably affects the risk of cancers of the upper
      aerodigestive tract.

PMID- 14578149
TI  - Detection of gastric cancer and premalignant lesions by novel marker glycoprotein
      87 using monoclonal antibody Adnab-9.
AB  - Gastric adenocarcinoma (GC), the second most frequent cancer in the world, is
      highly prevalent in Asia. A screening test for early-stage GC would represent a
      major advance in the management of this disease. Associated conditions such as
      chronic atrophic gastritis (CAG) with intestinal metaplasia are manifested by
      specialized intestinalized tissue that often includes Paneth cells. Adenoma
      associated antigen glycoprotein 87 (GP87), defined by the Adnab-9 monoclonal
      antibody and shed into the gut, is associated with epithelial cells, some of
      which resemble Paneth cells. We evaluated the diagnostic value of GP87 for cancer
      and gastric premalignant lesions. One hundred and seven sections of normal,
      benign, and premalignant gastric mucosa and 79 sections of pericancerous tissue
      were evaluated for expression of GP87 by immunohistochemistry. Eighty-two
      patients with GC, 34 patients with benign chronic disease, 35 patients with
      premalignant conditions, and 80 normal controls were evaluated by ELISA for GP87
      in feces and gastric juice. Adnab-9 immunostaining for GP87 was significantly
      positive in CAG and intestinal metaplasia (>77.8%), compared with 0% in normal
      controls (P < 0.05). Fecal GP87 was positive in 79.3% of patients with gastric
      cancer, including early-stage lesions, and in 84% of patients with CAG versus 10%
      of controls (P < 0.05). Positive proportions for each pathological group in
      tissue correlated with that in feces (r = 0.99; P < 0.02). GP87 is differentially
      expressed in premalignant gastric lesions that appear to be the origin for fecal
      GP87, which may be useful for early detection of GC.

PMID- 14578150
TI  - Nasopharyngeal carcinoma and genetic polymorphisms of DNA repair enzymes XRCC1
      and hOGG1.
AB  - Nitrosamine consumption and polymorphisms in CYP2E1, the product of which is
      involved in the activation of nitrosamines into reactive intermediates, have been
      shown to be associated with nasopharyngeal carcinoma (NPC) risk. Given that
      reactive intermediates created during nitrosamine metabolism are capable of DNA
      damage, we further hypothesized that differences between individuals in their
      ability to repair DNA damage might be important in NPC pathogenesis. To evaluate
      this hypothesis, this study focused on effects of genetic polymorphisms of DNA
      repair genes hOGG1 and XRCC1 on the development of NPC. We conducted a case
      control study to investigate the genotypes of 334 patients with NPC and 283
      healthy community controls matched by sex, age, and residence. The PCR-based RFLP
      assay was used to identify genetic polymorphisms. After adjustment for sex, age,
      and ethnicity, the odds ratio (OR) of developing NPC for hOGG1 codon 326
      genotypes of Ser/Cys and Cys/Cys compared with the Ser/Ser genotype was 1.6 (95%
      CI, 1.0-2.6). For XRCC1 codon 280 genotypes of Arg/His and His/His compared with
      the Arg/Arg genotype, the OR was 0.64 (95% CI, 0.43-0.96). Among subjects with
      putative high-risk genotypes for both hOGG1 and XRCC1, the OR was 3.0 (95% CI,
      1.0-8.8). Furthermore, subjects with putative high-risk genotypes for hOGG1,
      XRCC1, and CYP2E1 had an OR of disease of 25 (95% CI, 3.5-177). Polymorphisms of
      the DNA repair genes hOGG1 (codon 326) and XRCC1 (codon 280) are associated with
      an altered risk of NPC. Carriers of multiple putative high-risk genotypes have
      the highest risk of developing NPC.

PMID- 14578151
TI  - Changes in nonmelanoma skin cancer incidence between 1977-1978 and 1998-1999 in
      Northcentral New Mexico.
AB  - Nonmelanoma skin cancer (NMSC) is a highly common form of malignant disease in
      light-skinned populations. In 1977-1978, the National Cancer Institute sponsored
      a population-based skin cancer survey that found marked geographic variability in
      the incidence of NMSC within the United States. Some of the highest rates were
      observed in the southwestern state of New Mexico within its non-Hispanic white
      population. We recently undertook a follow-up survey of NMSC in New Mexico and
      report here incidence rate data for non-Hispanic white residents of a three
      county area in northcentral New Mexico for two 12-month time periods: June 1,
      1977 to May 31, 1978 and July 1, 1998 to June 31, 1999. Our results show that
      incidence rates of basal cell carcinoma increased by 50% in males and 20% in
      females, whereas rates of squamous cell carcinoma roughly doubled in both males
      and females. Temporal analysis of rates according to major anatomical site showed
      the head and neck was consistently the most frequent site of occurrence, however,
      the greatest percentage increase in rates over time occurred at the upper and
      lower limbs. These findings are consistent with those reported for various other
      populations showing the incidence of NMSC has measurably increased since the
      1970s.

PMID- 14578152
TI  - The HER2 I655V polymorphism and risk of breast cancer in women < age 40 years.
AB  - The HER2 gene controls cellular function and has prognostic significance in
      breast cancer. The I655V polymorphism was associated with increased risk of
      breast cancer in Chinese women under the age of 45 years and in women with a
      first-degree family history of the disease. These associations, however, have not
      been confirmed in several studies of older women. We conducted a population-based
      case-control-family study of the I655V polymorphism using 409 Australian women
      with breast cancer diagnosed before the age of 40 years and 299 controls
      frequency matched for age. The I655V polymorphism was more common in cases (P =
      0.01). A recessive model, in which homozygotes were associated with an adjusted
      odds ratio of 2.8 (95% confidence interval 1.3-6.2; P = 0.005), gave the best fit
      under parsimony. Although the biological role of the I655V polymorphism is not
      known, large independent studies of early onset breast cancer are warranted to
      attempt to replicate this finding.

PMID- 14578153
TI  - Evidence for a familial esophageal cancer susceptibility gene on chromosome 13.
AB  - Previous segregation analyses of pedigrees from areas of China where esophageal
      squamous cell carcinoma (ESCC) rates are extraordinarily high suggested a
      Mendelian mode of transmission. We initiated a search for a major ESCC gene by
      conducting a genome-wide scan in ESCC tumors. Chromosome 13 showed loss of
      heterozygosity (LOH) in 95% of microsatellite markers, the highest frequency of
      LOH on any chromosome. In the current study, we established a high-resolution
      deletion map using 107 markers on 13q and compared LOH frequency by family
      history of upper gastrointestinal cancer. Overall allelic loss was significantly
      higher in those with a positive (versus negative) family history, suggesting the
      presence of an inherited tumor suppressor gene on 13q in ESCC.

PMID- 14578154
TI  - Correspondence re: K. Toide et al., Aryl hydrocarbon hydroxylase represents
      CYP1B1, and not CYP1A1, in human freshly isolated white cells: trimodal
      distribution of Japanese population according to induction of CYP1B1 mRNA by
      environmental dioxins. 12: 219-222, 2003.

PMID- 14578156
TI  - Metabolism and DNA binding studies of 4-hydroxyestradiol and estradiol-3,4
      quinone in vitro and in female ACI rat mammary gland in vivo.
AB  - Studies of estrogen metabolism, formation of DNA adducts, carcinogenicity, cell
      transformation and mutagenicity have led to the hypothesis that reaction of
      certain estrogen metabolites, predominantly catechol estrogen-3,4-quinones, with
      DNA can generate the critical mutations initiating breast, prostate and other
      cancers. The endogenous estrogens estrone (E1) and estradiol (E2) are oxidized to
      catechol estrogens (CE), 2- and 4-hydroxylated estrogens, which can be further
      oxidized to CE quinones. To determine possible DNA adducts of E1(E2)-3,4-quinones
      [E1(E2)-3,4-Q], we reported previously that the reaction of E1(E2)-3,4-Q with dG
      produces the depurinating adduct 4-hydroxyE1(E2)-1-N7Gua [4-OHE1(E2)-1-N7Gua] by
      1,4-Michael addition (Stack et al., Chem. Res. Toxicol., 1996, 9, 851). We report
      here that reaction of E1(E2)-3,4-Q with Ade results in the formation of 4
      OHE1(E2)-1-N3Ade by 1,4-Michael addition. The N7Gua and N3Ade depurinating
      adducts formed both in vitro and in rat mammary gland in vivo were analyzed by
      HPLC with electrochemical detection and, for some samples, by LC/MS/MS. When E2
      3,4-Q was reacted with DNA in vitro, the depurinating adducts 4-OHE1(E2)-1-N3Ade
      and 4-OHE1(E2)-1-N7Gua, which are rapidly lost from DNA by cleavage of the
      glycosyl bond, were formed (>99% of the total adducts), as well as traces of
      stable adducts, which remain in DNA unless removed by repair. Similar results
      were obtained when 4-OHE2 was oxidized by horseradish peroxidase,
      lactoperoxidase, tyrosinase or phenobarbital-induced rat liver microsomes in the
      presence of DNA. When 4-OHE2 or E2-3,4-Q was injected into the mammary glands of
      female ACI rats in vivo and the mammary tissue was excised 1 h later, the
      depurinating adducts 4-OHE2-1-N3Ade and 4-OHE2-1-N7Gua constituted >99% of the
      total adducts formed. In addition, 4-OHE2 conjugates formed by reaction of E2-3,4
      Q with glutathione were also detected. These results demonstrate that the 4-CE
      are metabolized to CE-3,4-Q, which react with DNA to form primarily depurinating
      adducts. These adducts can generate the critical mutations that initiate cancer
      (Chakravarti et al., Oncogene, 2001, 20, 7945; Chakravarti et al., Proc. Am.
      Assoc. Cancer Res., 2003, 44, 180).

PMID- 14578157
TI  - Sulforaphane: a naturally occurring mammary carcinoma mitotic inhibitor, which
      disrupts tubulin polymerization.
AB  - Sulforaphane (SUL), an isothiocyanate found in broccoli and other cruciferous
      vegetables, has been shown to induce phase II detoxification enzymes, inhibit
      chemically induced mammary tumors in rats, and more recently to induce cell cycle
      arrest and apoptosis in cancer cells of the colon. Here, we provide evidence that
      SUL also acts as a breast cancer anti-proliferative agent. The BALB/c mouse
      mammary carcinoma cell line F3II was treated with SUL at concentrations up to 15
      microM and examined for markers of cell cycle arrest and apoptosis. Treatment of
      asynchronous F3II cells with 15 microM SUL resulted in G2/M cell cycle arrest,
      elevated p34cdc2 (cdc2) kinase activity, Bcl-2 down-regulation, evidence of
      caspase activation, and aggregation of condensed nuclear chromatin. Subsequent
      exposure of synchronized cells to 15 microM SUL resulted in elevated numbers of
      prophase/prometaphase mitotic figures, indicating cell cycle progression beyond
      G2 and arrest early within mitosis. Moreover, cells treated with 15 microM SUL
      displayed aberrant mitotic spindles, and higher doses of SUL inhibited tubulin
      polymerization in vitro. In addition, BALB/c mice injected s.c. with F3II cells
      and subsequently injected daily i.v. with SUL (15 nmol/day for 13 days) developed
      significantly smaller tumors (approximately 60% less in mass) than vehicle
      treated controls. Western blot analysis of tumor proteins demonstrated
      significantly (P<0.05) reduced PCNA and elevated PARP fragmentation in samples
      from animals dosed with SUL. Taken together, these results indicate that SUL has
      mammary cancer suppressive actions both in cell culture and in the whole animal.
      Inhibition of mammary carcinogenesis appears in part to involve perturbation of
      mitotic microtubules and early M-phase block associated with cdc2 kinase
      activation, indicating that cells arrest prior to metaphase exit.

PMID- 14578158
TI  - Gene expression profiling in respiratory tissues from rats exposed to mainstream
      cigarette smoke.
AB  - Cigarette smoke (CS) is known to cause cancer and other diseases, but little is
      known about the global molecular and cellular changes that occur prior to the
      appearance of clinically detectable symptoms. Using DNA microarrays covering 2031
      cDNA probes, we investigated differential gene expression in tissues of the rat
      respiratory tract, i.e. respiratory nasal epithelium (RNE) and lungs of rats
      exposed either acutely (3 h) or subchronically (3 h/day, 5 days/week, 3 weeks) to
      mainstream CS with death either immediately or at 20 h after exposure.
      Differential gene expression was most evident in RNE of rats exposed once and was
      characterized by strong up-regulation of genes encoding oxidative stress
      responsive and Phase II drug-metabolizing enzymes, such as haem oxygenase-1 and
      NAD(P)H:quinone oxidoreductase, which are all, at least in part,
      transcriptionally regulated by NF-E2-related factor 2 (Nrf2). After 3 weeks of
      exposure, the strength of expression of this class of genes was markedly reduced,
      pointing to an adaptive response. The generally lower response in the lungs of
      exposed rats is indicative of a deposition gradient of active smoke constituents
      from the upper to the lower respiratory tract. In sharp contrast to the CS
      induced expression of oxidative stress and Phase II-responsive genes, induction
      of the genes encoding the Phase I drug-metabolizing enzymes cytochrome P450
      (CYP)1A1 and aldehyde dehydrogenase-3 was not reduced after 3 weeks of exposure
      and was similarly high in lungs and RNE. Gene expression patterns in rats allowed
      to recover for 20 h showed that the CS-induced transcriptional changes observed
      immediately after exposure returned almost completely to normal, even after 3
      weeks of repeated CS exposure. In general, these results demonstrate that CS
      induces a specific differential gene expression pattern in vivo, which may be
      instrumental in identifying the molecular mechanisms leading to the onset of
      inflammatory and/or morphological changes.

PMID- 14578159
TI  - Grapefruit juice intake does not enhance but rather protects against aflatoxin B1
      induced liver DNA damage through a reduction in hepatic CYP3A activity.
AB  - Influence of grapefruit juice intake on aflatoxin B1 (AFB1)-induced liver DNA
      damage was examined using a Comet assay in F344 rats given 5 mg/kg AFB1 by
      gavage. Rats allowed free access to grapefruit juice for 5 days prior to AFB1
      administration resulted in clearly reduced DNA damage in liver, to 65% of the
      level in rats that did not receive grapefruit juice. Furthermore, rats treated
      with grapefruit juice extract (100 mg/kg per os) for 5 days prior to AFB1
      treatment also reduced the DNA damage to 74% of the level in rats that did not
      receive grapefruit juice. No significant differences in the portal blood and
      liver concentrations of AFB1 were observed between grapefruit juice intake rats
      and the controls. In an Ames assay with AFB1 using Salmonella typhimurium TA98,
      lower numbers of revertant colonies were detected with hepatic microsomes
      prepared from rats administered grapefruit juice, compared with those from
      control rats. Microsomal testosterone 6beta-hydroxylation was also lower with
      rats given grapefruit juice than with control rats. Immunoblot analyses showed a
      significant decrease in hepatic CYP3A content, but not CYP1A and CYP2C content,
      in microsomes of grapefruit juice-treated rats than in non-treated rats. No
      significant difference in hepatic glutathione S-transferase (GST) activity and
      glutathione content was observed in the two groups. GSTA5 protein was not
      detected in hepatic cytosol of the two groups. In microsomal systems, grapefruit
      juice extract inhibited AFB1-induced mutagenesis in the presence of a microsomal
      activation system from livers of humans as well as rats. These results suggest
      that grapefruit juice intake suppresses AFB1-induced liver DNA damage through
      inactivation of the metabolic activation potency for AFB1 in rat liver.

PMID- 14578160
TI  - Involvement of the PI 3-kinase signaling pathway in progression of colon
      adenocarcinoma.
AB  - The phosphoinositide 3-kinase (PI 3-kinase) signaling pathway has been shown to
      play a pivotal role in intracellular signal transduction pathways involved in
      cell growth, cellular transformation and tumorigenesis. Analysis of several colon
      adenocarcinoma cell lines indicates that the PI 3-kinase signaling pathway is up
      regulated in colon cancers. In particular, the protein levels and phosphorylation
      status of Akt and p70 S6 kinase are up-regulated in colon adenocarcinoma cell
      lines. More significantly, we have demonstrated for the first time that the
      phosphorylation of FKHR, a downstream target of Akt, is increased in these cell
      lines. Intriguingly, phosphorylation of three components of the PI 3-kinase
      signaling pathway, namely Akt, p70 S6 kinase and FKHR, are in direct correlation
      with the degree of tumorigenic potential of the colon cell lines tested. No
      differences in the protein levels of the two subunits of PI 3-kinase, p85 and
      p110alpha, and PTEN were noted. Real-time quantitative PCR indicated an increase
      in levels of Akt message only, and not of the other signaling pathway components.
      Inhibition of the PI 3-kinase with wortmannin decreased the anchorage-independent
      growth of colon cells in a soft agar assay. Hence, the components of the PI 3
      kinase signaling pathway could serve as potential candidates for drug development
      in treatment of colon cancer.

PMID- 14578161
TI  - Effect of chemopreventive agents on separate stages of progression of
      benzo[alpha]pyrene induced lung tumors in A/J mice.
AB  - The effects of aerosol budesonide and dietary myo-inositol on progression of
      benzo[alpha]pyrene (B[alpha]P) induced carcinogenesis were studied in A/J mouse
      lung. First, we determined when to intervene in the carcinogenesis process by
      exposing several animals to B[alpha]P at 100 and 150 mg/kg of body wt. Groups of
      these animals were necropsied from 1 to 36 weeks post-carcinogen. The presence of
      different categories of lung tumors was noted over the 36 week time period.
      Hyperplasia first appeared approximately 6 weeks post-carcinogen followed by
      adenoma at 9 weeks, then by carcinoma at 26 weeks. From this temporal sequence we
      determined we could test for effects of preventive agents on progression to
      hyperplasia by intervening at 3 weeks, for effects on progression to adenoma by
      intervening at 6 weeks and for effects on progression to carcinoma by
      intervention at 12 weeks. Intervention at 3 weeks post-carcinogen with
      aerosolized budesonide delayed both hyperplasia and adenoma formation. Once
      hyperplasia appeared in budesonide treated animals, however, it increased at the
      same rate as in control animals, indicating a delay in progression. Progression
      from adenoma to carcinoma was reduced when budesonide was given 12 weeks post
      carcinogen. Dietary myo-inositol failed to suppress progression from adenoma to
      carcinoma when started 12 weeks post-carcinogen. In summary, budesonide is a
      chemopreventive agent that has inhibitory effects on B[alpha]P induced
      carcinogenesis of the lung in A/J mice at all stages of progression from
      hyperplasia formation to cancer.

PMID- 14578162
TI  - Dietary genistein results in larger MNU-induced, estrogen-dependent mammary
      tumors following ovariectomy of Sprague-Dawley rats.
AB  - Due to the estrogenic properties of soy-derived isoflavones, many postmenopausal
      women are using these compounds as a natural alternative to hormone replacement
      therapy (HRT). How isoflavones impact breast cancer in postmenopausal women is
      important, because a majority of breast cancer cases occur in this age group.
      Chemical induction of mammary tumors in female rats has been used to determine
      that exposure of the mammary gland to soy isoflavones prior to tumor induction is
      protective against tumor formation. Here we investigate the effect of dietary
      genistein on mammary tumors that have already formed. The study was designed to
      determine the action of dietary genistein in a low endogenous estrogen
      environment as is observed in postmenopausal women. Animals were ovariectomized
      (OVX) after mammary tumor development and were then placed into one of three
      treatment groups: positive-control (OVX+ estradiol implant), genistein (OVX+ 750
      p.p.m. genistein) and negative-control (OVX alone). Tumors were distinguished as
      malignant or benign by histopathological examination and were further
      characterized as either estrogen-dependent or estrogen-independent using
      immunohistochemistry to identify the presence of both estrogen receptor (ER)
      alpha and the progesterone receptor (PR). Genistein at 750 p.p.m. increased the
      weight of estrogen-dependent adenocarcinomas in ovariectomized rats compared with
      the negative-control animals. Genistein treatment also resulted in a higher
      percentage of proliferative cells in tumors and increased uterine weights when
      compared with negative-control animals. Collectively, these effects are probably
      due to the estrogenic activity of genistein. Plasma genistein concentrations in
      animals fed the isoflavone-containing diet were at physiological levels relevant
      to human exposure. Estradiol concentrations in ovariectomized animals not
      receiving an estradiol supplement were similar to those observed in
      postmenopausal women. The data suggest that in an endogenous estrogen environment
      similar to that of a postmenopausal woman, dietary genistein can stimulate the
      growth of a mammary carcinogen MNU-induced estrogen-dependent mammary tumors.

PMID- 14578163
TI  - Effect of arsenic on benzo[a]pyrene DNA adduct levels in mouse skin and lung.
AB  - Concomitant exposures to arsenic and polycyclic aromatic hydrocarbons (PAHs) such
      as benzo[a]pyrene (BaP) are widespread. While BaP acts by binding to and inducing
      mutations in critical sites on DNA, the mechanism(s) of arsenic carcinogenesis
      remains unknown. Data from epidemiological studies of arsenic copper smelter
      workers and arsenic ingestion in drinking water suggest a positive interaction
      for arsenic exposure and smoking and lung cancer. A previous in vitro study
      showed that arsenic potentiated the formation of DNA adducts at low doses of BaP
      and arsenic. The present study was conducted to test the effect of arsenic on BaP
      DNA adduct formation in vivo. We hypothesized that arsenic co-treatment would
      significantly increase BaP adduct levels in C57BL/6 mouse target organs: skin and
      lung. Treatment groups were: five mice, -BaP/-arsenic; five mice, -BaP/+arsenic;
      15 mice, +BaP/-arsenic; 15 mice, +BaP/+arsenic. Mice in the appropriate groups
      were provided sodium arsenite in drinking water (2.1 mg/l), ad libitum, for 13
      days (starting 9 days before BaP treatment), and 200 nmol BaP/25 ml acetone (or
      acetone alone) was applied topically, once per day for 4 days. DNA was extracted
      from skin and lung and assayed by (32)P-postlabeling. Statistical comparisons
      were made using independent t-tests (unequal variances assumed). BaP-DNA adduct
      levels in the +BaP groups were significantly higher than -BaP controls. Arsenic
      co-treatment increased average BaP adduct levels in both lung and skin; the
      increase was statistically significant in the lung (P = 0.038). BaP adduct levels
      in the skin of individual animals were positively related to skin arsenic
      concentrations. These results corroborate our in vitro findings and provide a
      tentative explanation for arsenic and PAH interactions in lung carcinogenesis.

PMID- 14578164
TI  - Polymorphisms in DNA double-strand break repair genes and breast cancer risk in
      the Nurses' Health Study.
AB  - Genetic polymorphisms in double-strand break repair genes may influence DNA
      repair capacity and, in turn, confer predisposition to breast cancer. We
      prospectively assessed the associations of candidate polymorphisms G31479A
      (R188H) in XRCC2, A4541G (5'-UTR), A17893G (IVS5-14) and C18067T (T241 M) in
      XRCC3, and C299T (5'-UTR) and T1977C (D501D) in Ligase IV with breast cancer risk
      in a nested case-control study within the Nurses' Health Study (incident cases,
      n=1004; controls, n=1385). We observed no overall associations of these six
      genotypes with breast cancer risk. Four common haplotypes in XRCC3 accounted for
      99% of the chromosomes of the present study population. We observed that Ligase
      IV 1977C carriers were at increased breast cancer risk if they had a first degree
      family history of breast cancer (test for interaction, P=0.01). We observed that
      the XRCC2 R188H polymorphism modified the association of plasma alpha-carotene
      level and breast cancer risk (test for ordinal interaction, P=0.03); the
      significantly decreased risk seen overall for women in the highest quartile of
      plasma alpha-carotene was only present among 188H non-carriers (the top quartile
      versus the bottom quartile; multivariate odds ratio, 0.55; 95% confidence
      interval, 0.40-0.75). No significant interactions were seen between any of these
      polymorphisms and duration or dose of cigarette smoking. The gene-environment
      interaction data suggest that the subtle effects of some of these variants on
      breast cancer risk may be magnified in the presence of certain exposures.

PMID- 14578165
TI  - RING protein Trim32 associated with skin carcinogenesis has anti-apoptotic and E3
      ubiquitin ligase properties.
AB  - Tripartite motif protein 32, Trim32, mRNA and protein expression was elevated in
      independently transformed and tumorigenic keratinocytes of a mouse epidermal
      carcinogenesis model, in ultraviolet B (UVB)-induced squamous cell carcinomas
      (SCC), and in approximately 20-25% of chemically induced mouse papillomas and
      human head and neck SCCs. This suggests that elevated Trim32 expression occurs
      frequently in experimental epidermal carcinogenesis and is relevant to human
      cancer. Transduced Trim32 increased colony number in an epidermal in vitro
      transformation assay and epidermal thickening in vivo when skin-grafted to
      athymic nu/nu mice. These effects were not associated with proliferation and were
      not sufficient for tumorigenesis, even with 12-O-tetradecanoylphorbol-13-acetate
      treatment or defects in the tumor suppressor p53. However, transduced Trim32
      inhibited the synergistic effect of tumor necrosis factor alpha (TNFalpha) on UVB
      induced apoptosis of keratinocytes in vitro and the apoptotic response of
      keratinocyte grafts exposed to UVB-light in vivo. Consistent with its RING
      domain, Trim32 exhibited characteristics of E3-ubiquitin ligases, including being
      ubiquitylated itself and interacting with ubiquitylated proteins, with increases
      in these properties following treatment of cultured keratinocytes with
      TNFalpha/UVB. Interestingly, missense point mutation of human TRIM32 has been
      reported in Limb-Girdle Muscular Dystrophy Type 2H, an autosomal recessive
      disease. We propose a model in which Trim32 activities as an E3-ubiquitin ligase
      favor initiated cell survival in carcinogenesis by blocking UVB-induced TNFalpha
      apoptotic signaling.

PMID- 14578166
TI  - Phosphorylation state-specific antibodies: applications in investigative and
      diagnostic pathology.
AB  - Until recently, the investigation of protein phosphorylation was limited to
      biochemical studies of enzyme activities in homogenized tissues. The availability
      of hundreds of phosphorylation state-specific antibodies (PSSAs) now makes
      possible the study of protein phosphorylation in situ, and is opening many
      exciting opportunities in investigative and diagnostic pathology. This review
      illustrates the power of PSSAs, especially in immunohistochemical applications to
      human disease and animal models. Technical considerations, including antibody
      specificity and lability of phosphoepitopes, are covered, along with potential
      pitfalls, illustrated by a case study. In the arena of oncology, PSSAs may prove
      especially valuable in directly demonstrating the efficacy of chemotherapies
      targeted at protein kinase cascades. Novel applications of PSSAs are also
      beginning to reveal molecular mechanisms of inflammatory, degenerative, and toxin
      induced diseases.

PMID- 14578167
TI  - Exposing a killer: pathologists angle for anthrax.

PMID- 14578168
TI  - Comparative neuropathology and diabetic autonomic neuropathy.

PMID- 14578169
TI  - Beta-catenin mutations are frequent in calcifying odontogenic cysts, but rare in
      ameloblastomas.
AB  - We have reported previously that alterations to beta-catenin occur frequently in
      adamantinomatous craniopharyngioma. Based on its histological resemblance to some
      odontogenic tumors, we suspected the presence of common genetic alterations among
      these tumors. To address this issue, 11 cases of calcifying odontogenic cyst
      (COC) and 20 cases of ameloblastoma were investigated for the presence of beta
      catenin mutations and beta-catenin expression. Ten COCs were successfully
      analyzed by direct sequencing, and nine of them were found to harbor somatic beta
      catenin mutations. Immunohistochemically, all of the COCs showed nuclear and
      cytoplasmic expression of beta-catenin with a heterogeneous pattern. No beta
      catenin mutations were found in ameloblastomas, except for one case of the
      follicular type. All follicular ameloblastomas exhibited moderate nuclear and
      cytoplasmic accumulation of beta-catenin, in contrast to the predominantly
      membranous expression seen in the plexiform type. beta-Catenin mutation is
      considered to be a characteristic genetic feature of COC, and may play a critical
      role in its histogenesis. Although ameloblastoma closely resembles COC
      histologically, the two have genetically distinctive features.

PMID- 14578170
TI  - Introduction of estrogen receptor-alpha into the tTA/TAg conditional mouse model
      precipitates the development of estrogen-responsive mammary adenocarcinoma.
AB  - Conditional expression of estrogen receptor (ER)-alpha) was introduced into
      tetracycline-responsive MMTV-tTA/tetop-TAg mice to develop a mouse model of
      estrogen-responsive ER-alpha-positive mammary adenocarcinoma. Mammary
      adenocarcinomas developed in the mice with a mean latency of 11 months. Precursor
      lesions including ductal hyperplasia and hyperplastic alveolar nodules were
      present by the age of 4 months. The mammary adenocarcinomas exhibited
      histological features similar to human breast cancers. ER steroid-binding studies
      conducted on adenocarcinoma lysates demonstrated binding to estradiol. Tumor
      explant studies in the presence and absence of estradiol in ovariectomized
      athymic nude mice revealed that growth of mammary tumors was stimulated by
      estrogen. In addition, the presence of ER-alpha altered the tumor spectrum in
      other MMTV-targeted tissues in the tTA/TAg female mice. Lymphomas, which develop
      in 40% of tTA/TAg female mice, were found in only 4% of tTA/TAg/ER-alpha mice (P
      = 0.014, chi-square test). These experiments demonstrate that the introduction of
      an ER-alpha transgene targeted to mammary epithelial cells can be used to develop
      mouse models of ER-alpha-responsive mammary cancer.

PMID- 14578172
TI  - p53 haploinsufficiency profoundly accelerates the onset of tongue tumors in mice
      lacking the xeroderma pigmentosum group A gene.
AB  - Mice lacking the xeroderma pigmentosum group A gene (XPA-/- mice), which have a
      complete deficiency in nucleotide excision repair (NER), are highly predisposed
      to tongue squamous cell carcinoma (SCC) when exposed to 4-nitroquinoline 1-oxide
      (4NQO). To explore the effects of the interaction of the NER machinery with p53
      in oral tumorigenesis, we generated an XPA-/- mouse strain carrying mutant
      alleles for p53. This mouse model of 4NQO carcinogenesis demonstrated that
      despite the same tumor frequency, XPA-/-p53+/- mice reached 100% SCC incidence at
      25 weeks compared with 50 weeks for XPA-/-p53+/+ littermates. XPA-/-p53-/- mice
      succumbed to spontaneous thymic lymphomas before the development of tongue tumors
      (before 13 weeks of age). SCC originated in XPA-/-p53+/- mice maintained the
      p53+/- genotype and the retained wild-type p53 allele appeared to be structurally
      intact. Only one of 20 XPA-/-p53+/+ SCC showed a missense mutation of p53.
      Collectively, the accelerated tongue tumor growth may be a consequence of
      haploinsufficiency but not of mutation of p53 in the context of NER deficiency.

PMID- 14578171
TI  - Gene expression patterns in ependymomas correlate with tumor location, grade, and
      patient age.
AB  - To elucidate the molecular events responsible for tumorigenesis and progression
      of ependymomas, we analyzed molecular alterations on the gene expression level in
      a series of newly diagnosed ependymal neoplasms (n = 39). To this aim, tumor RNA
      was hybridized to microarrays comprising 2600 different genes with relevance to
      mitosis, cell-cycle control, oncogenesis, or apoptosis. For CLU, IGF-2, and RAF
      1, which are apparent candidate genes because they had been previously described
      to be involved in tumorigenesis of other human malignancies, we found a high
      expression on the mRNA as well as the protein level. We identified gene
      expression signatures for the differentiation of tumors with respect to location,
      grade, and patient age. Spinal ependymomas were characterized by high-expression
      levels of HOXB5, PLA2G, and CDKN2A and tumors in young patients (< or =16 years
      of age) by high-expression levels of LDHB and STAM. Notably, we were able to
      classify supratentorial grade II and III tumors with 100% accuracy, whereas this
      did not apply for infratentorial ependymomas. The similar gene expression
      patterns of grade II and III infratentorial malignancies suggest that grade III
      tumors may develop through a secondary multistep transformation process involving
      genes that are related to cell proliferation (LDHA, cyclin B, MAT2A) or tumor
      suppression (PTEN). In summary, our results provide new insight in the
      biochemical pathways particularly intriguing in the pathomechanism of ependymomas
      and suggest that this entity comprises molecularly distinct diseases.

PMID- 14578173
TI  - Susceptibility to anthrax lethal toxin is controlled by three linked quantitative
      trait loci.
AB  - Anthrax lethal toxin (LT) is the principal virulence factor associated with
      lethal pathologies following infection with Bacillus anthracis. Macrophages are
      the primary effector cells mediating lethality since macrophage-depleted mice are
      resistant to LT challenge. Recently, Ltxs1, the gene controlling differential
      susceptibility of murine macrophages to cytolysis following in vitro exposure to
      LT, was identified as Kif1c. To directly assess the in vivo role of Kif1c alleles
      in mortality, we studied a panel of interval-specific recombinant congenic lines
      carrying various segments of central chromosome 11 derived from LT-resistant
      DBA/2 mice on the LT-susceptible BALB/c background. The results of this study
      reveal that mortality is controlled by three linked quantitative trait loci
      (QTL): Ltxs1/Kif1c (42-43 cM), Ltxs2 (35-37 cM), and Ltxs3 (45-47 cM). The Ltxs3
      interval encompasses Nos2, which is an attractive candidate gene for Ltxs3. In
      this regard, we demonstrate that selective, pharmacologically based inhibition of
      Nos2 activity in vivo partially overrides genetic resistance to LT and that Nos2
      expression as determined by reverse transcription-polymerase chain reaction
      differs significantly between DBA/2 and BALB/c macrophages. Additionally, to
      recapitulate dominant resistance to mortality as seen in (BALB/c x DBA/2) F(1)
      hybrids, DBA/2 alleles are required at all three QTL.

PMID- 14578174
TI  - Function and structure of pressurized and perfused porcine carotid arteries:
      effects of in vitro balloon angioplasty.
AB  - In this report we describe the application of an in vitro pressure-perfusion
      system for study of functional/structural changes after in vitro balloon dilation
      injury. Pig carotid arteries were perfused at P = 100 mm Hg and Q = 100 ml/min,
      balloon angioplastied (BA), and cultured under these hemodynamic conditions for 4
      or 8 days (n = 5 BA and 6 controls for each time point). To assess endothelial
      function, outer diameter changes in response to bradykinin (BK) were measured
      daily. Remodeling was determined from the shift in pressure-passive diameter
      relation, as obtained after papaverine addition. Arterial samples were processed
      for histology. Control arteries showed spontaneous tone, BK-induced relaxation,
      and inward remodeling that was more pronounced at day 8 (ratio end-to-start
      passive diameter at P = 100 mm Hg, 0.69 +/- 0.04; P < 0.001) than at day 4 (0.85
      +/- 0.03, P = 0.03). Intimal hyperplasia was detectable in these control vessels
      at day 8 with accumulation of alpha-smooth muscle actin-positive cells around the
      lumen. Angioplasty caused ruptures and dissections and abolished tone that
      returned after 5 days of perfusion along with BK-dependent relaxation. No
      significant inward remodeling or intimal hyperplasia was observed at day 8 after
      angioplasty. Thus, BA inhibits remodeling, which occurs after in vitro perfusion
      of conductance arteries.

PMID- 14578175
TI  - Quantifying telomere lengths of human individual chromosome arms by centromere
      calibrated fluorescence in situ hybridization and digital imaging.
AB  - Telomere length analysis has aroused considerable interest in biology and
      oncology. However, most published data are pan-genomic Southern-blot-based
      estimates. We developed T/C-FISH (telomere/centromere-FISH), allowing precise
      measurement of individual telomeres at every single chromosome arm. Metaphase
      preparations are co-hybridized with peptide nucleic acid probes for telomeric
      sequences and the chromosome 2 centromere serving as internal reference.
      Metaphase images are captured and karyotyped using dedicated software. A software
      module determines the absolute integrated fluorescence intensities of the p- and
      q-telomeres of each chromosome and the reference signal. Normalized data are
      derived by calculating the ratio of absolute telomere and reference signal
      intensities, and descriptive statistics are calculated. T/C-FISH detects even
      small differences in telomere length. Using T/C-FISH we have discovered an
      epigenetic process occurring in the human male postzygote or early embryo: in
      umbilical cord blood lymphocytes, telomeres on male Xqs are around 1100 bp
      shorter than female Xqs.

PMID- 14578176
TI  - Spontaneous aberrant crypt foci in Apc1638N mice with a mutant Apc allele.
AB  - The Apc1638N/+ mouse has a chain-terminating mutation in one allele of the
      adenomatous polyposis coli (Apc) gene that is similar to most mutations observed
      in the human familial adenomatous polyposis syndrome. Aberrant crypt foci (ACF),
      the earliest identified neoplastic lesions in the colon, are morphologically
      abnormal structures that are identifiedmicroscopically in the grossly normal
      colonic mucosas of rodents treated with colon carcinogens and of human patients.
      The colons and cecums of 62 Apc1638N/+ mice were evaluated for the spontaneous
      occurrence of ACF and tumors. Both male and female mice were killed at different
      times between 5 and 28 weeks of age. Wild-type littermates, ie, Apc(+/+) mice, at
      22 to 26 weeks of age served as controls. ACF were identified in 97% of the
      Apc1638N/+ mice starting at 5 weeks of age and not in any wild-type littermates.
      Although the number of ACF increased with age (P < 0.0001), the average number of
      crypts per focus of the ACF did not increase significantly. In addition, wild
      type Apc protein was detected by immunohistochemistry in all 22 ACF evaluated.
      Together these data suggest that heterozygous loss of Apc may be sufficient to
      initiate ACF in these mice and that these mice may be suitable models to study
      the interaction of environmental factors with an inherited mutation of the Apc
      gene that is associated with colon cancer.

PMID- 14578177
TI  - Classifying melanocytic tumors based on DNA copy number changes.
AB  - Melanoma and benign melanocytic nevi can overlap significantly in their
      histopathological presentation and misdiagnoses are common. To determine whether
      genetic criteria can be of diagnostic help we determined DNA copy number changes
      in 186 melanocytic tumors (132 melanomas and 54 benign nevi) using comparative
      genomic hybridization. We found highly significant differences between melanomas
      and nevi. Whereas 127 (96.2%) of the melanomas had some form of chromosomal
      aberration, only 7 (13.0%) of the benign nevi cases had aberrations. All seven
      cases with aberrations were Spitz nevi, in six of which the aberration was an
      isolated gain involving the entire short arm of chromosome 11. This aberration
      was not observed in any of the 132 melanomas. We also analyzed the 132 melanomas
      for genetic differences depending on anatomical site, Clark's histogenetic type,
      and sun-exposure pattern. We show that melanomas on acral sites have
      significantly more aberrations involving chromosomes 5p, 11q, 12q, and 15, as
      well as focused gene amplifications. Melanomas classified as lentigo maligna
      melanomas or as occurring on severely sun-damaged skin showed markedly more
      frequent losses of chromosomes 17p and 13q. This study shows a pattern of
      chromosomal aberration in melanoma that is distinct from melanocytic nevi and
      should be further evaluated as a diagnostic test for melanocytic lesions that are
      now ambiguous. In addition, we show marked differences in the genetic make-up of
      melanomas that depend on anatomical location and sun-exposure pattern indicating
      that potential therapeutic targets might vary among melanoma types.

PMID- 14578178
TI  - Recessive epidermolysis bullosa simplex phenotype reproduced in vitro: ablation
      of keratin 14 is partially compensated by keratin 17.
AB  - Recessive epidermolysis bullosa simplex (REBS) is characterized by generalized
      cutaneous blistering in response to mechanical trauma. This results from
      fragility of the basal keratinocytes that lack keratin tonofilaments because of
      homozygote null mutation in the keratin 14 gene. REBS patients display in
      addition focal dyskeratotic skin lesions with histology of epidermolytic
      hyperkeratosis (EHK) and tonofilament clumping in the suprabasal layers of the
      epidermis. In this study we examined whether it is possible to mimic in vitro the
      bullous and dyskeratotic cellular phenotype. For this purpose, fibroblasts from
      nondyskeratotic (K14-/-) and dyskeratotic (K14-/-) skin of a REBS patient and
      fibroblasts from a healthy donor (K14+/+) were isolated and incorporated into
      collagen matrices. Subsequently, fresh biopsies originating from the
      nondyskeratotic and dyskeratotic skin of the patient and from a healthy donor
      were placed onto the collagen matrices and cultured at the air-liquid interface.
      Epidermal morphogenesis was evaluated on the basis of tissue morphology and the
      expression of a series of keratins. The results of the present study indicate
      that basal cell vacuolization in REBS can be mimicked in vitro but not the EHK.
      Fibroblasts seem to play an important regulatory role in establishing the REBS
      phenotype. These findings suggest that wild-type fibroblasts may enhance the
      stability of K14-/- keratinocytes in vitro.

PMID- 14578179
TI  - Human SPF45, a splicing factor, has limited expression in normal tissues, is
      overexpressed in many tumors, and can confer a multidrug-resistant phenotype to
      cells.
AB  - Our effort to identify novel drug-resistant genes in cyclophosphamide-resistant
      EMT6 mouse mammary tumors led us to the identification of SPF45. Simultaneously,
      other groups identified SPF45 as a component of the spliceosome that is involved
      in alternative splicing. We isolated the human homologue and examined the normal
      human tissue expression, tumor expression, and the phenotype caused by
      overexpression of human SPF45. Our analyses revealed that SPF45 is expressed in
      many, but not all, normal tissues tested with predominant expression in normal
      ductal epithelial cells of the breast, liver, pancreas, and prostate. Our
      analyses using tissue microarrays and sausages of tumors indicated that SPF45 is
      highly expressed in numerous carcinomas including bladder, breast, colon, lung,
      ovarian, pancreatic, and prostate. Interestingly, this study revealed that
      overexpression of SPF45 in HeLa, a cervical carcinoma cell line, resulted in drug
      resistance to doxorubicin and vincristine, two chemotherapeutic drugs commonly
      used in cancer. To our knowledge, this is the first study showing tumor
      overexpression of an alternate splicing factor resulting in drug resistance.

PMID- 14578180
TI  - Beta4 integrin and laminin 5 are aberrantly expressed in polycystic kidney
      disease: role in increased cell adhesion and migration.
AB  - Extracellular matrix alterations have been suggested to be part of the early
      events occurring in Autosomal Dominant Polycystic Kidney Disease (ADPKD), a
      disease characterized by formation of renal cysts and progressive renal failure.
      Here we report that cDNA array analysis identified beta(4) integrin aberrant
      expression in ADPKD cells. Furthermore, laminin 5 (Ln-5), the main
      alpha(6)beta(4) integrin ligand, was also found to be abnormally expressed in
      ADPKD. Studies performed with ADPKD cyst-lining epithelial cells (CC) by
      comparison with normal tubular cells indicate that integrin alpha(6)beta(4)-Ln-5
      interactions are involved in cellular events of potential importance for
      cystogenesis: 1) laminin 5 is a preferential adhesion substrate for CC, mainly
      through alpha(6)beta(4) interaction, 2) CC increased haptotactic and chemotactic
      motility depends on the presence of Ln-5 and requires integrin alpha(3)beta(1)
      cooperation, and 3) CC haptotactic or chemotactic migration is specifically
      increased by mAb-mediated beta(4) integrin ligation, through an alpha(3)beta(1)
      integrin-dependent and independent pathway, respectively. These results highlight
      the role of Ln-5 and alpha(6)beta(4) integrin in adhesive and motility properties
      of cyst-lining epithelial cells, and further suggest that integrins and
      extracellular matrix modifications may be of general relevance to kidney
      epithelial cell cyst formation.

PMID- 14578181
TI  - Abnormalities of basement membrane on blood vessels and endothelial sprouts in
      tumors.
AB  - Often described as incomplete or absent, the basement membrane of blood vessels
      in tumors has attracted renewed attention as a source of angiogenic and anti
      angiogenic molecules, site of growth factor binding, participant in angiogenesis,
      and potential target in cancer therapy. This study evaluated the composition,
      extent, and structural integrity of the basement membrane on blood vessels in
      three mouse tumor models: spontaneous RIP-Tag2 pancreatic islet tumors, MCa-IV
      mammary carcinomas, and Lewis lung carcinomas. Tumor vessels were identified by
      immunohistochemical staining for the endothelial cell markers CD31, endoglin
      (CD105), vascular endothelial growth factor receptor-2, and integrin alpha5
      (CD49e). Confocal microscopic studies revealed that basement membrane identified
      by type IV collagen immunoreactivity covered >99.9% of the surface of blood
      vessels in the three tumors, just as in normal pancreatic islets. Laminin,
      entactin/nidogen, and fibronectin immunoreactivities were similarly ubiquitous on
      tumor vessels. Holes in the basement membrane, found by analyzing 1- micro m
      confocal optical sections, were <2.5 micro m in diameter and involved only 0.03%
      of the vessel surface. Despite the extensive vessel coverage, the basement
      membrane had conspicuous structural abnormalities, including a loose association
      with endothelial cells and pericytes, broad extensions away from the vessel wall,
      and multiple layers visible by electron microscopy. Type IV collagen
      immunoreactive sleeves were also present on endothelial sprouts, supporting the
      idea that basement membrane is present where sprouts grow and regress. These
      findings indicate that basement membrane covers most tumor vessels but has
      profound structural abnormalities, consistent with the dynamic nature of
      endothelial cells and pericytes in tumors.

PMID- 14578182
TI  - 12E2: a cloned murine dermal cell with features of dermal dendrocytes and
      capacity to produce pathologic changes resembling early Kaposi's sarcoma.
AB  - Factor XIIIa-positive dendrocytes are abundant within the dermis and have been
      implicated in the pathogenesis of various disorders, including AIDS-related
      Kaposi's sarcoma. Purified cultures of factor XIIIa-positive normal dermal
      dendrocytes have not as yet been achieved. 12E2 is a cloned cell line derived
      from superficial murine dermis where factor XIIIa-positive dendrocytes are
      abundant. Subconfluent cultures of 12E2 demonstrate polydendritic cell contours
      with thin, elongated membranous projections. These cells express Factor XIIIa and
      VCAM-1 by immunohistochemistry and by Western blot analysis of 12E2 cell lysates.
      12E2 cells also constitutively express the Langerhans-cell-related epitope DEC
      205, detected by NLDC-145 antibody and the CD80 co-stimulatory molecule, as well
      as Ia antigen on exposure to interferon-gamma. Cells so treated exhibit
      significant ability to present alloantigens in vitro. 12E2 cells are shown to
      express mRNA for numerous cytokines, including interleukin (IL)-1alpha, IL-1beta,
      IL-5, IL-6, IL-7, tumor necrosis factor-alpha and granulocyte macrophage-colony
      stimulating factor, by reverse-transcriptase polymerase chain reaction followed
      by Southern blot hybridization. Microinjection of 12E2 cells, but not 3T3control
      fibroblasts, into footpads of syngeneic and SCID mice results in lesions that
      mimic the histology and immunohistochemistry of human Kaposi's sarcoma. In
      aggregate, these data indicate that 12E2 cells 1) share lineage characteristics
      with factor XIIIa-positive dermal dendrocytes, 2) produce mRNA for numerous
      cytokines and are cytokine responsive to interferon-gamma, and 3) behave in vivo
      in a manner that resembles Kaposi's sarcoma, a condition known to involve
      proliferation of human dermal dendrocytes.

PMID- 14578183
TI  - Collagen type II-specific monoclonal antibody-induced arthritis in mice:
      description of the disease and the influence of age, sex, and genes.
AB  - Transfer of collagen type II (CII)-specific monoclonal antibodies induces an
      acute form of arthritis (collagen type II antibody-induced arthritis, CAIA) in
      naive mice. Arthritis was induced using a pair of monoclonal antibodies M2139 and
      CIIC1, binding to J1 and C1(I) epitopes of CII, respectively. Thereafter,
      lipopolysaccharide injection was used to increase the incidence and severity of
      the disease. This model was used to investigate the effect of genes, age, and sex
      as well as effector cells in the end-stage effector phase of arthritis
      pathogenesis. Injection of a single monoclonal antibody induced arthritis only
      after lipopolysaccharide stimulation. CAIA showed differences in disease
      penetration among the susceptible strains indicating the importance of non-major
      histocompatibility complex genes on the antibody effector pathway. B-cell
      deficient mice were susceptible to CAIA and in some genetic backgrounds B-cell
      deficiency leads to enhanced arthritis. Histology of the affected paws revealed
      massive infiltrations of neutrophils along with bone and cartilage erosion,
      pannus formation, and fibrin deposition. Depletion of neutrophils significantly
      reduced the incidence and severity of the disease. CAIA susceptibility increased
      with age. Males were more susceptible than females and estrogen treatment
      decreased the development of arthritis. We conclude that CAIA is an acute
      arthritis triggered by antibody binding and neutrophils bypassing immune
      activation but with many characteristics in common with collagen-induced
      arthritis.

PMID- 14578184
TI  - The inhibitory receptor FcgammaRII reduces joint inflammation and destruction in
      experimental immune complex-mediated arthritides not only by inhibition of
      FcgammaRI/III but also by efficient clearance and endocytosis of immune
      complexes.
AB  - Studies of FcgammaRII-/- mice identified the inhibitory function of this receptor
      in joint inflammation and cartilage destruction induced with immune complexes
      (ICs). To extend our insight in the role of FcgammaRII in arthritis, we explored
      the role of FcgammaRII in the absence of activating receptors I and III using
      FcgammaRI/III-/- as well as FcgammaRI/II/III-/- mice. When antigen-induced
      arthritis (AIA) was elicited, which is a mixture of T cell and IC-driven
      inflammation, arthritis was almost absent at day 7 in FcgammaRI/III-/- mice.
      Remarkably, in FcgammaRI/II/III-/- mice, this model induced a tremendously
      increased arthritis as compared to wild-type controls. This implies that
      FcgammaRII regulates joint inflammation also in the absence of activating
      FcgammaRI and III. To confirm the IC specificity of this finding, similar studies
      were done with ICs or zymosan as arthritogenic stimuli. Strongly elevated
      inflammation was found in FcgammaRI/II/III-/- mice with IC but not with zymosan.
      Clearance studies identified accumulation of IgG in the knee joint in the absence
      of FcgammaRII. Moreover, macrophages expressing only FcgammaRII showed prominent
      endocytosis of preformed soluble ICs not different from controls. In total
      absence of FcgammaR (FcgammaRI/II/III-/-), macrophages completely failed to
      endocytose ICs. Although joint inflammation was much higher in AIA arthritic knee
      joints of FcgammaRI/II/III-/- and the inflammatory cells still expressed an
      inflammatory phenotype, severe cartilage destruction (MMP-mediated neoepitopes in
      the matrix and chondrocyte death) was completely prevented in contrast to the
      marked destruction which was observed in the wild-type. Our study indicates that
      FcgammaRII reduces joint inflammation in the absence of activating FcgammaR by
      promoting endocytosis and clearance of ICs from the joint. Infiltrating cells,
      which fail to express activating FcgammaR although they still become stimulated
      are no longer capable of inducing severe cartilage destruction.

PMID- 14578185
TI  - Hepatocytes express nerve growth factor during liver injury: evidence for
      paracrine regulation of hepatic stellate cell apoptosis.
AB  - A key feature of recovery from liver fibrosis is hepatic stellate cell (HSC)
      apoptosis, which serves the dual function of removing the major source of
      neomatrix and tissue inhibitors of metalloproteinases thereby facilitating matrix
      degradation. The mechanisms regulating HSC apoptosis remain undefined but may
      include the interaction of nerve growth factor (NGF) with its receptor, p75, on
      HSC. In this study, by TaqMan polymerase chain reaction in situ hybridization and
      immunohistochemistry, we demonstrate that NGF is expressed by hepatocytes during
      fibrotic injury. Peak hepatocyte expression of NGF (48 hours after CCl(4)
      injection) coincides with maximal rate of apoptosis of HSC by terminal dUTP nick
      end labeling staining. Addition of recombinant NGF to HSC in tissue culture
      causes a dose-dependent increase in apoptosis. NGF regulates nuclear factor (NF)
      kappaB activity, reducing p50/p65 binding detected by electromobility shift assay
      and reduced NF-kappaB CAT reporter activities from both basal unstimulated levels
      and after NF-kappaB induction by tumor necrosis factor. In each case, a relative
      reduction in NF-kappaB binding was associated with a significant increase in
      caspase 3 activity. These data provide evidence that NGF is expressed during
      fibrotic liver injury and may regulate number of activated HSCs via induction of
      apoptosis.

PMID- 14578186
TI  - In vivo interrogation of the molecular display of atherosclerotic lesion
      surfaces.
AB  - The endothelial surface of atherosclerotic lesions of ApoE knockout mice was
      interrogated by in vivo biopanning with a phage-displayed constrained peptidyl
      library. Through repeated biopanning, 103 peptidyl sequences were identified,
      many are homologous to known proteins. The sequence CAPGPSKSC contains motifs
      that are shared by 9.7% of selected peptides. On phage or as a synthetic peptide,
      this constrained peptide selectively bound to atherosclerotic lesion surfaces of
      ApoE knockout mice in vivo and of human atherosclerotic lesions ex vivo. A cell
      surface protein of approximately 82 kd recognized by this peptide was affinity
      purified and determined by mass spectrometry analysis as glucose-regulated
      protein 78 (Grp78), indicating the surprising presence of this endoplasmic
      reticulum chaperone on the endothelial cell surface of atherosclerotic lesions.
      Peptides that mimicked binding functions of their homologues were demonstrated
      with three peptides homologous to tissue inhibitor of metalloproteinase-2 (TIMP
      2), ie, CNHRYMQMC, CNQRHQMSC, and CNNRSDGMC. Phage carrying CNHRYMQMC bound to
      atherosclerotic lesion endothelium of ApoE knockout mice in vivo. The three
      peptides bound to endothelial cells in a dose-dependent manner and were inhibited
      by TIMP-2 protein. These peptides provide a set of probes to interrogate the cell
      surface repertoire associated with atherogenesis and thrombotic complications.

PMID- 14578187
TI  - Implications of glucose transporter protein type 1 (GLUT1)-haplodeficiency in
      embryonic stem cells for their survival in response to hypoxic stress.
AB  - Glucose transporter protein type 1 (GLUT1) is a major glucose transporter of the
      fertilized egg and preimplantation embryo. Haploinsufficiency for GLUT1 causes
      the GLUT1 deficiency syndrome in humans, however the embryo appears unaffected.
      Therefore, here we produced heterozygous GLUT1 knockout murine embryonic stem
      cells (GT1+/-) to study the role of GLUT1 deficiency in their growth, glucose
      metabolism, and survival in response to hypoxic stress. GT1(-/-) cells were
      determined to be nonviable. Both the GLUT1 and GLUT3 high-affinity, facilitative
      glucose transporters were expressed in GT1(+/+) and GT1(+/-) embryonic stem
      cells. GT1(+/-) demonstrated 49 +/- 4% reduction of GLUT1 mRNA. This induced a
      posttranscriptional, GLUT1 compensatory response resulting in 24 +/- 4% reduction
      of GLUT1 protein. GLUT3 was unchanged. GLUT8 and GLUT12 were also expressed and
      unchanged in GT1(+/-). Stimulation of glycolysis by azide inhibition of oxidative
      phosphorylation was impaired by 44% in GT1(+/-), with impaired up-regulation of
      GLUT1 protein. Hypoxia for up to 4 hours led to 201% more apoptosis in GT1(+/-)
      than in GT1(+/+) controls. Caspase-3 activity was 76% higher in GT1(+/-) versus
      GT1(+/+) at 2 hours. Heterozygous knockout of GLUT1 led to a partial GLUT1
      compensatory response protecting nonstressed cells. However, inhibition of
      oxidative phosphorylation and hypoxia both exposed their increased susceptibility
      to these stresses.

PMID- 14578188
TI  - The myofibroblast is the predominant plasminogen activator inhibitor-1-expressing
      cell type in human breast carcinomas.
AB  - The tumor level of plasminogen activator inhibitor-1 (PAI-1) is an informative
      biochemical marker of a poor prognosis in several cancer types. However, the
      tumor biological functions of PAI-1 and the identity of PAI-1-expressing cells
      are controversial. With the aim of immunohistochemically localizing PAI-1 in
      formalin-fixed, paraffin-embedded invasive ductal breast carcinoma samples, we
      raised new polyclonal antibodies against PAI-1 from different expression systems.
      The antibodies were affinity purified by absorption on immobilized preparations
      of PAI-1 different from those used for immunization. The specificity of the
      antibodies was ensured by immunoblotting analysis. In immunohistochemistry, the
      staining pattern obtained with the antibodies showed a good correlation with the
      PAI-1 mRNA expression pattern. In all 25 cases analyzed, PAI-1 immunoreactivity
      was predominantly localized in fibroblast-like cells. Double-immunofluorescence
      analyses showed co-expression of PAI-1 and alpha-smooth muscle actin in these
      cells, suggesting that they are myofibroblasts. PAI-1 was also seen in some
      myoepithelial cells surrounding occasional foci of ductal carcinoma in situ (9 of
      25), some endothelial cells (8 of 25), some cancer cells (3 of 25), and some mast
      cells (6 of 25). In conclusion, we have provided a robust immunohistochemical
      procedure for detection of PAI-1 and shown that the majority of the PAI-1
      expressing cells in invasive ductal breast carcinomas are myofibroblasts.

PMID- 14578189
TI  - The critical role of pathology in the investigation of bioterrorism-related
      cutaneous anthrax.
AB  - Cutaneous anthrax is a rare zoonotic disease in the United States. The clinical
      diagnosis traditionally has been established by conventional microbiological
      methods, such as culture and gram staining. However, these methods often yield
      negative results when patients have received antibiotics. During the bioterrorism
      event of 2001, we applied two novel immunohistochemical assays that can detect
      Bacillus anthracis antigens in skin biopsy samples even after prolonged
      antibiotic treatment. These assays provided a highly sensitive and specific
      method for the diagnosis of cutaneous anthrax, and were critical in the early and
      rapid diagnosis of 8 of 11 cases of cutaneous anthrax during the outbreak
      investigation. Skin biopsies were obtained from 10 of these 11 cases, and
      histopathological findings included various degrees of ulceration, hemorrhage,
      edema, coagulative necrosis, perivascular inflammation, and vasculitis. Serology
      was also an important investigation tool, but the results required several weeks
      because of the need to test paired serum specimens. Other tests, including
      culture, special stains, and polymerase chain reaction assay, were less valuable
      in the diagnosis and epidemiological investigation of these cutaneous anthrax
      cases. This report underscores the critical role of pathology in investigating
      potential bioterrorism events and in guiding epidemiological studies, a role that
      was clearly demonstrated in 2001 when B. anthracis spores were intentionally
      released through the United States postal system.

PMID- 14578190
TI  - Cell-type-specific repression of the maspin gene is disrupted frequently by
      demethylation at the promoter region in gastric intestinal metaplasia and cancer
      cells.
AB  - Maspin, a serine protease inhibitor, was originally reported as a tumor
      suppressor gene in breast and prostatic cancers. We examined maspin expression
      and/or the allele-specific methylation status in four gastric cancer cell lines,
      as well as normal, metaplastic, and cancerous epithelia obtained from 50 gastric
      cancer patients. Three gastric cancer cell lines exhibiting maspin overexpression
      showed hypomethylation at either both alleles or a haploid allele. Only one cell
      line (GCIY) was maspin-negative but maspin expression was reactivated after
      treatment with a demethylating agent, 5-aza-2'-deoxycytidine. Dense and diffuse
      immunoreactivity for maspin was observed in 40 (80%) of 50 gastric cancers and
      all gastric normal epithelia (GNE) with intestinal metaplasia (IM), but not in
      GNE without IM. We further analyzed the allele-specific methylation status in 10
      of 50 cases subjected to immunohistochemistry by the crypt isolation technique
      followed by a bisulfite genome sequencing method. The maspin gene promoter region
      of all GNE without IM was hypermethylated on both alleles whereas those with IM
      frequently represented the haploid type of hypomethylation status. In six of
      seven gastric cancers in which crypt isolation was possible, demethylation
      frequently occurred and extended to both alleles. Maspin mRNA was amplified from
      GNE with IM and cancerous crypts but not from GNE without IM. These results
      suggest that demethylation at the maspin gene promoter disrupts the cell-type
      specific gene repression in both GNE and gastric cancer.

PMID- 14578191
TI  - Overexpression of semicarbazide-sensitive amine oxidase in smooth muscle cells
      leads to an abnormal structure of the aortic elastic laminas.
AB  - Elevated semicarbazide-sensitive amine oxidase (SSAO) activity has been observed
      in several human conditions, eg, diabetes, and it has been speculated that SSAO
      contributes to the development of vasculopathies associated with this disease. To
      investigate in vivo consequences of elevated expression of SSAO in vascular
      tissues, we have developed a transgenic model for overexpression of human SSAO in
      mice. A smooth muscle-specific promoter, smooth muscle alpha-actin promoter 8
      (SMP8) was used. Transgenic expression of human SSAO in tissues with a high
      content of smooth muscle cells was confirmed by Northern blot analysis. Enzymatic
      analysis of homogenates from transgenic tissues showed elevated levels of SSAO
      activity compared to non-transgenic littermates. Furthermore, when plasma SSAO
      activity was analyzed, much higher activity was detected compared to plasma from
      control mice, indicating that plasma SSAO may originate from smooth muscle cells.
      Histopathological evaluation of aorta and renal artery from transgenic mice
      revealed an abnormal structure of the elastin tissue. Instead of the regularly
      folded elastic laminae normally found in tunica media of sacrificed mice, the
      elastic laminae were straight and unfolded with irregularly arranged elastic
      fibers, forming tangled webs, between the intercalating elastic laminae. These
      alterations of the elastin structures suggest that overexpression of SSAO has led
      to a reduced elasticity of the arteries. Moreover, the mean femoral arterial
      pressure of the SMP8 SSAO transgenic mice was significantly lower in comparison
      to non-transgenic littermates. This suggests that the transgenic mice have a
      defect in their ability to regulate blood pressure.

PMID- 14578192
TI  - Loss of calpain-3 autocatalytic activity in LGMD2A patients with normal protein
      expression.
AB  - The diagnosis of limb girdle muscular dystrophy (LGMD) type 2A (due to mutations
      in the gene encoding for calpain-3) is currently based on protein analysis, but
      mutant patients with normal protein expression have also been identified. In this
      study we investigated 150 LGMD patients with normal calpain-3 protein expression,
      identified gene mutations by an allele-specific polymerase chain reaction test,
      and analyzed the mutant calpain-3 catalytic activity. Four different mutations
      were found in eight patients (5.5%): a frame-shifting deletion (550 A del) and
      three missense (R490Q, R489Q, R490W). Patients with normal calpain-3 protein
      expression on Western blot are a considerable proportion (20%) of our total
      LGMD2A population. While in control muscle the calpain-3 Ca(++)-dependent
      autocatalytic activity was evident within 5 minutes and was prevented by ethylene
      diaminetetraacetic acid, in all mutant patient samples the protein was not
      degraded, indicating that the normal autocatalytic function had been lost. By
      this new functional test, we show that conventional protein diagnosis fails to
      detect some mutant proteins, and prove the pathogenetic role of R490Q, R489Q,
      R490W missense mutations. We suggest that these mutations impair protein activity
      by affecting interdomain protein interaction, or reduce autocatalytic activity by
      lowering the Ca(++) sensitivity.

PMID- 14578193
TI  - Angiotensin II increases connective tissue growth factor in the kidney.
AB  - Connective tissue growth factor (CTGF) has been described as a novel fibrotic
      mediator. CTGF is overexpressed in several kidney diseases and is induced by
      different factors involved in renal injury. Angiotensin II (AngII) participates
      in the pathogenesis of kidney damage, contributing to fibrosis; however, whether
      AngII regulates CTGF in the kidney has not been explored. Systemic infusion of
      AngII into normal rats for 3 days increased renal CTGF mRNA and protein levels.
      At day 7, AngII-infused rats presented overexpression of CTGF in glomeruli,
      tubuli, and renal arteries, as well as tubular injury and elevated fibronectin
      deposition. Only treatment with an AT(1) receptor antagonist, but not an AT(2),
      diminished CTGF and fibronectin overexpression and ameliorated tubular damage. In
      rats with immune complex nephritis, renal overexpression of CTGF was diminished
      by the ACE inhibitor quinapril, correlated with a diminution in fibrosis. In
      cultured renal cells (mesangial and tubular epithelial cells) AngII, via AT(1),
      increased CTGF mRNA and protein production, and a CTGF antisense oligonucleotide
      decreased AngII-induced fibronectin synthesis. Our data show that AngII regulates
      CTGF in the kidney and cultured in mesangial and tubular cells. This novel
      finding suggests that CTGF could be a mediator of the profibrogenic effects of
      AngII in the kidney.

PMID- 14578194
TI  - Non-small-cell lung cancer molecular signatures recapitulate lung developmental
      pathways.
AB  - Current paradigms hold that lung carcinomas arise from pleuripotent stem cells
      capable of differentiation into one or several histological types. These
      paradigms suggest lung tumor cell ontogeny is determined by consequences of gene
      expression that recapitulate events important in embryonic lung development.
      Using oligonucleotide microarrays, we acquired gene profiles from 32
      microdissected non-small-cell lung tumors. We determined the 100 top-ranked
      marker genes for adenocarcinoma, squamous cell, large cell, and carcinoid using
      nearest neighbor analysis. Results were validated by immunostaining for 11
      selected proteins using a tissue microarray representing 80 tumors. Gene
      expression data of lung development were accessed from a publicly available
      dataset generated with the murine Mu11k genome microarray. Self-organized mapping
      identified two temporally distinct clusters of murine orthologues. Supervised
      clustering of lung development data showed large-cell carcinoma gene orthologues
      were in a cluster expressed in pseudoglandular and canalicular stages whereas
      adenocarcinoma homologues were predominantly in a cluster expressed later in the
      terminal sac and alveolar stages of murine lung development. Representative large
      cell genes (E2F3, MYBL2, HDAC2, CDK4, PCNA) are expressed in the nucleus and are
      associated with cell cycle and proliferation. In contrast, adenocarcinoma genes
      are associated with lung-specific transcription pathways (SFTPB, TTF-1), cell
      adhesion, and signal transduction. In sum, non-small-cell lung tumors histology
      gene profiles suggest mechanisms relevant to ontogeny and clinical course.
      Adenocarcinoma genes are associated with differentiation and glandular formation
      whereas large-cell genes are associated with proliferation and differentiation
      arrest. The identification of developmentally regulated pathways active in
      tumorigenesis provides insights into lung carcinogenesis and suggests early steps
      may differ according to the eventual tumor morphology.

PMID- 14578195
TI  - Interleukin-12-independent down-modulation of cockroach antigen-induced asthma in
      mice by intranasal exposure to bacterial lipopolysaccharide.
AB  - Several studies have shown that exposure to bacterial lipopolysaccharide (LPS)
      can either prevent or inhibit asthma in humans and laboratory rodents. Much
      emphasis has been placed on the role of cytokines and chemokines in the
      establishment and maintenance of allergic airway disease. Therefore, it is of
      interest to study the role of LPS in affecting airway pathology and lung cytokine
      and chemokine responses in the maintenance phase of asthma. Increasing doses of
      LPS were administered into the airways of mice presensitized with cockroach
      allergen (CRAg), then allergic airway disease parameters were assessed after CRAg
      challenge. Airway hyperresponsiveness after antigen challenge decreased at the
      highest dose of LPS tested, which was accompanied by a decrease in airway and
      lung eosinophils. However, a dramatic increase in lung inflammation because of
      neutrophil influx was observed. Measurement of cytokines in lungs of LPS-treated,
      CRAg-sensitized mice indicated that interleukin (IL)-12 levels were increased by
      LPS treatment in a dose-dependent manner, as were levels of several inflammatory
      chemokines. In contrast, levels of IL-4, IL-13, IL-5, and IL-10 were reduced in
      whole lung homogenates only of high-dose LPS-treated mice. Intranasal
      administration of neutralizing anti-IL-12 at the time of high-dose LPS challenge
      reduced lung IL-12, interferon-gamma, CXCL9, and CXCL10 but did not affect levels
      of the other chemokines or Th2-type cytokines, and did not restore AHR. These
      findings suggest that the amelioration of airway hyperresponsiveness observed in
      LPS-treated, CRAg-sensitized mice is coincident with an immune deviation of the
      lung inflammatory response, independent of IL-12.

PMID- 14578197
TI  - Amplification of a 280-kilobase core region at the ERBB2 locus leads to
      activation of two hypothetical proteins in breast cancer.
AB  - Amplification of the ERBB2 oncogene at 17q12 is clinically the most relevant
      genetic aberration in breast cancer and several studies have linked ERBB2
      activation to poor clinical outcome. The development of targeted antibody-based
      therapy for ERBB2-overexpressing tumors and the possible role of ERBB2 as a
      predictor of chemotherapy treatment response have further emphasized the
      essential role of ERBB2 in breast cancer. Here, we performed a detailed
      characterization of the molecular events occurring at the ERBB2 amplicon in
      primary breast tumors. Analysis of the amplicon structure in 330 breast tumors by
      fluorescence in situ hybridization to a tissue microarray revealed a 280-kb
      common region of amplification that contains 10 transcribed sequences, including
      eight known genes. The expression levels of these 10 transcripts were determined
      in 36 frozen samples of grade-matched ERBB2-amplified and -nonamplified (as
      determined by fluorescence in situ hybridization) primary breast tumors by using
      quantitativereal-time reverse transcriptase-polymerase chain reaction. A highly
      significant association between amplification and expression levels was observed
      for six of these genes, including ERBB2 and two uncharacterized hypothetical
      proteins, MGC9753 and MGC14832. These results support the recent findings on the
      influence of copy number on gene expression levels and highlight novel genes that
      might contribute to the clinical behavior of ERBB2-amplified breast tumors.

PMID- 14578196
TI  - Interferon-gamma increases hPepT1-mediated uptake of di-tripeptides including the
      bacterial tripeptide fMLP in polarized intestinal epithelia.
AB  - Interferon-gamma causes a global phenotypic switch in intestinal epithelial
      function, in which enterocytes become immune accessory cells. The phenotypic
      switch is characterized by a down-regulation of membrane transporters and up
      regulation of immune accessory molecules in intestinal epithelial cells. However,
      the effect of interferon-gamma on the intestinal epithelia di-tripeptide hPepT1
      transporter has not been investigated. In this study we demonstrate that 1)
      interferon-gamma increases di-tripeptide uptake in dose- and time-dependent
      manner in model intestinal epithelia (Caco-2 BBE cell monolayers), 2) the
      increase in di-tripeptides induced by interferon-gamma is hPepT1 mediated, 3)
      interferon-gamma does not affect the hPept1 expression at the mRNA and protein
      levels 4) interferon-gamma increases the intracellular pH and consequently
      enhances the H+-electrochemical gradient across apical plasma membrane in model
      intestinal epithelia (Caco2-BBE monolayers). We suggest that interferon-gamma
      could increase the hPepT1 mediated di-tripeptides uptake in inflamed epithelial
      cells. Under these conditions, interferon-gamma will increase the intracellular
      amount of such diverse prokaryotic and eucaryotic small di-tripeptides in
      inflamed epithelial cells. The intracellular accumulation of such di-tripeptides
      may be important in enterocytes becoming immune accessory cells.

PMID- 14578198
TI  - Accurate molecular classification of human cancers based on gene expression using
      a simple classifier with a pathological tree-based framework.
AB  - Recent studies suggest accurate prediction of tissue of origin for human cancers
      can be achieved by applying sophisticated statistical learning procedures to gene
      expression data obtained from DNA microarrays. We have pursued the hypothesis
      that a more straightforward and equally accurate strategy for classifying human
      tumors is to use a simple algorithm that considers gene expression levels within
      a tree-based framework that encodes limited information about pathology and
      tissue ontogeny. By considering gene expression data within this framework, we
      found only a small number of genes were required to achieve a relatively high
      accuracy level in tumor classification. Using as few as 45 genes we were able to
      classify 157 of 190 human malignant tumors correctly, which is comparable to
      previous results obtained with sophisticated classifiers using thousands of
      genes. Our simple classifier accurately predicted the origin of metastatic tumors
      even when the classifier was trained using only primary tumors, and the
      classifier produced accurate predictions when trained and tested on expression
      data from different labs, and from different microarray platforms. Our findings
      suggest that accurate and robust cancer diagnosis from gene expression profiles
      can be achieved by mimicking the classification strategies routinely used by
      surgical pathologists.

PMID- 14578199
TI  - Neuroprotective effect of (-)Delta9-tetrahydrocannabinol and cannabidiol in N
      methyl-D-aspartate-induced retinal neurotoxicity: involvement of peroxynitrite.
AB  - In glaucoma, the increased release of glutamate is the major cause of retinal
      ganglion cell death. Cannabinoids have been demonstrated to protect neuron
      cultures from glutamate-induced death. In this study, we test the hypothesis that
      glutamate causes apoptosis of retinal neurons via the excessive formation of
      peroxynitrite, and that the neuroprotective effect of the psychotropic Delta9
      tetrahydroxycannabinol (THC) or nonpsychotropic cannabidiol (CBD) is via the
      attenuation of this formation. Excitotoxicity of the retina was induced by
      intravitreal injection of N-methyl-D-aspartate (NMDA) in rats, which also
      received 4-hydroxy-2,2,6,6-tetramethylpiperidine-n-oxyl (TEMPOL,a superoxide
      dismutase-mimetic), N-omega-nitro-L-arginine methyl ester (L-NAME, a nitric oxide
      synthase inhibitor), THC, or CBD. Retinal neuron loss was determined by TDT
      mediated dUTP nick-end labeling assay, inner retinal thickness, and
      quantification of the mRNAs of ganglion cell markers. NMDA induced a dose- and
      time-dependent accumulation of nitrite/nitrate, lipid peroxidation, and
      nitrotyrosine (foot print of peroxynitrite), and a dose-dependent apoptosis and
      loss of inner retinal neurons. Treatment with L-NAME or TEMPOL protected retinal
      neurons and confirmed the involvement of peroxynitrite in retinal neurotoxicity.
      The neuroprotection by THC and CBD was because of attenuation of peroxynitrite.
      The effect of THC was in part mediated by the cannabinoid receptor CB1. These
      results suggest the potential use of CBD as a novel topical therapy for the
      treatment of glaucoma.

PMID- 14578200
TI  - Differential expression of metallothionein 1 and 2 isoforms in breast cancer
      lines with different invasive potential: identification of a novel nonsilent
      metallothionein-1H mutant variant.
AB  - Metallothionein (MT), a low-molecular weight protein with pleiotropic functions,
      is believed to play an important role in tumorigenesis. The aim of this study was
      to compare the expression of functional MT-1 and MT-2 mRNA isoforms in five
      breast cancer cell lines ranging from noninvasive MCF7 breast cancer cells to
      highly aggressive MDA-MB-231 breast cancer cells together with breast
      myoepithelial cells in vitro by conventional semiquantitative reverse
      transcriptase-polymerase chain reaction (RT-PCR) and quantitative real-time RT
      PCR. The MT-2A isoform was observed to be differentially upregulated in the
      invasive phenotype. The MT-1E isoform was found to be present in estrogen
      receptor-negative breast cancer cell lines (MDA-MB-231 and Hs578T) but not
      detectable in the estrogen receptor-positive cell lines (T47D, MCF7, and ZR75-1
      cells). Only the myoepithelial cells exhibited the presence of the MT-1G
      transcript. Direct sequencing of the RT-PCR products revealed the occurrence of a
      variant MT-1H isoform with changes in amino acid residues in the protein sequence
      and notable differences in the predicted secondary protein structure. The
      observations in this study are relevant to the development of novel approaches to
      metastatic breast cancer disease, and may herald the search for novel MT mutants
      and the elucidation of their biological roles.

PMID- 14578201
TI  - Receptor activator of nuclear factor kappaB ligand (RANKL)/osteoprotegerin (OPG)
      ratio is increased in severe osteolysis.
AB  - Pathological osteolyses are considered a consequence of a disturbance in the
      mechanisms that govern the bone remodeling, mainly the communication between
      osteoclasts and osteoblasts. Osteoprotegerin (OPG) and receptor activator of NF
      kappaB ligand (RANKL) are newly discovered molecules that play a key role in
      these communications. RANKL is essential for osteoclast differentiation via its
      receptor RANK located on the osteoclast membrane. OPG is a soluble decoy receptor
      that inhibits osteoclast differentiation through its binding to RANKL. The aim of
      this study is the analysis of the RANKL/OPG balance by complementary methods
      (semiquantitative reverse transcription-polymerase chain reaction,
      immunohistochemistry, and enzyme-linked immunosorbent assay) in human osteolysis
      associated to various bone etiologies (n = 60), tumoral (primitive, secondary) or
      not, compared to healthy tissues (n = 16). Results demonstrated that RANKL/OPG
      ratio was significantly increased in patients suffering from severe osteolysis
      compared to the control group and that this imbalance is involved in bone
      resorption mechanisms. In this study, OPG expression appears to reflect a
      protective mechanism of the skeleton to compensate increased bone resorption by
      inhibiting osteoclast formation and bone resorbing activity. Moreover, as
      revealed by immunohistochemistry, RANKL and OPG were colocalized in all of the
      tissues analyzed. To define the veracity of RANKL/OPG index in assessing and
      managing patients with severe osteolysis, an extended population of patients
      suffering from severe osteolysis must be now monitored.

PMID- 14578202
TI  - Heterogeneity of macrophage activation in anti-Thy-1.1 nephritis.
AB  - Macrophages infiltrating glomeruli in telescoped nephrotoxic nephritis are
      programmed. The purpose of this study was to assess whether macrophages
      infiltrating glomeruli of rats with passively induced injury become similarly
      programmed, and to determine whether macrophage commitment is an early event.
      Glomerular macrophages isolated from rats with resolving and proliferative anti
      Thy-1 nephritis were examined for nitric oxide (NO) generation and expression of
      lysosomal hydrolases. After a single injection of Thy-1 antibody the cells
      generated large amounts of NO that was attenuated ex vivo by transforming growth
      factor-beta and other anti-inflammatory cytokines. In contrast macrophages
      infiltrating glomeruli immediately after a second injection of Thy-1 antibody
      generated NO spontaneously and were unresponsive to alternative activation. beta
      Glucuronidase expression was used as a second independent assay for macrophage
      activation and the results confirmed the observations made for NO. Furthermore,
      macrophages infiltrating the glomerulus after the second antibody injection
      exhibited a striking dichotomy in that 70% of the cells behave as programmed by
      interferon-gamma and 30% by transforming growth factor-beta. The results show
      that macrophage commitment occurs very early after monocyte migration and that
      infiltration itself does not invariably induce macrophage programming. It
      demonstrates that macrophages infiltrating inflamed glomeruli at the same time do
      not respond uniformly, but are capable of engaging different activation programs.
      This emphasizes the critical importance of the underlying disease process for
      macrophage functional development in an inflamed environment.

PMID- 14578203
TI  - Mediation of transforming growth factor-beta(1)-stimulated matrix contraction by
      fibroblasts: a role for connective tissue growth factor in contractile scarring.
AB  - Excessive cell-mediated tissue contraction after injury can lead to morbid
      contractile scarring in the body. In the eye this can cause blindness because of
      posterior capsule opacification, proliferative vitroretinopathy, failure of
      glaucoma filtration surgery, and corneal haze. During repair, transforming growth
      factor (TGF)-beta and connective tissue growth factor (CTGF) genes are co
      ordinately expressed. Although TGF-beta and CTGF stimulate new matrix deposition,
      their role and regulation during contractile scarring is unknown. In this study,
      an in vitro model of collagen matrix contraction culminating from tractional
      forces generated by fibroblasts showed that both TGF-beta(1) and CTGF-stimulated
      contraction. Using a specific anti-sense oligodeoxynucleotide to CTGF the
      procontractile activity of TGF-beta(1) was found to be mediated by CTGF. During
      contraction fibroblasts produced similar levels of matrix metalloproteinases
      (MMPs)-2 and -9 with TGF-beta(1) or CTGF and a modest increase in MMP-1 with CTGF
      only (indicated by zymography and enzyme-linked immunosorbent assay). The
      requirement of MMPs for contraction was demonstrated using a broad-spectrum
      synthetic inhibitor. This study demonstrates a new function for CTGF in mediating
      matrix contraction by fibroblasts involving MMPs and suggests a novel regulatory
      mechanism for TGF-beta-stimulated contraction. Inhibition of CTGF activity or
      gene transcription could be a suitable target for anti-scarring therapies.

PMID- 14578204
TI  - The combination of calmodulin antagonists and interferon-gamma induces apoptosis
      through caspase-dependent and -independent pathways in cholangiocarcinoma cells.
AB  - Calmodulin (CaM) antagonists have been shown to inhibit tumor cell invasion and
      metastasis and to induce apoptosis in various tumor models, but the molecular
      mechanism of CaM antagonist-mediated apoptosis is poorly understood. Here, we
      demonstrate that interferon (IFN)-gamma induces susceptibility to CaM antagonist
      mediated apoptosis in human cholangiocarcinoma cells weakly expressing Fas (Fas
      low cells). During CaM antagonist-mediated apoptosis in IFN-gamma-pretreated Fas
      low cells, cleavage of caspases-8, -9, and -3 and Bid, release of cytochrome c
      from the mitochondria and an increase in the free cytosolic calcium concentration
      were observed. CaM antagonists also caused depolarization of the mitochondrial
      membrane independent of caspase activation. Although a broad-range caspase
      inhibitor partially blocked CaM antagonist-mediated apoptosis, the neutralizing
      Fas antibody had no effect, suggesting that CaM antagonist-mediated apoptosis
      does not require interaction between CaM antagonists and surface Fas. CaM
      antagonists induce apoptosis via mechanisms other than inhibition of CaM
      dependent protein kinase II and calcineurin, as their inhibitors, KN93 and
      cyclosporine A, had no effect on apoptosis. Taken together, these results
      indicate that CaM antagonists induce apoptosis in both caspase-dependent and 
      independent manners, and that susceptibility to CaM antagonists is modulated by
      IFN-gamma. The combination of IFN-gamma and CaM antagonists, including tamoxifen,
      may be a potential therapeutic modality for cholangiocarcinoma and possibly other
      malignancies.

PMID- 14578205
TI  - PARC/CCL18 is a plasma CC chemokine with increased levels in childhood acute
      lymphoblastic leukemia.
AB  - Chemokines play an important role in leukocyte mobilization, hematopoiesis, and
      angiogenesis. Tissue-specific expression of particular chemokines also influences
      tumor growth and metastasis. Here, the CC chemokine pulmonary and activation
      regulated chemokine (PARC)/CCL18 was measured in pediatric patients with acute
      lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML). Surprisingly, PARC
      immunoreactivity was consistently detected in plasma from healthy donors. After
      purification to homogeneity, the presence of intact PARC (1-69) and processed
      PARC (1-68) in normal human plasma was confirmed by sequence and mass
      spectrometry analysis. Furthermore, PARC serum levels were significantly
      increased in children with T-ALL and prepreB-ALL compared to control serum
      samples, whereas serum levels in AML and preB-ALL patients were not significantly
      different from controls. In contrast, the hemofiltrate CC chemokine-1 (HCC
      1)/CCL14 was not found to be a biomarker in any of these patients' strata,
      whereas the cytokine interleukin-6 (IL-6) was significantly decreased in AML and
      prepreB-ALL. Stimulated leukocytic cell lines or lymphoblasts from patients
      produced IL-8/CXCL8 or macrophage inflammatory protein-1alpha (MIP-1alpha/CCL3)
      but not PARC, not even after IL-4 or IL-10 treatment. However, PARC was produced
      by superantigen or IL-4 stimulated monocytes co-cultured with lymphocytes or
      lymphoblastic cells. Serum PARC levels thus constitute a novel leukemia marker,
      possibly reflecting tumor/host cell interactions in the circulation.

PMID- 14578206
TI  - Non-obese diabetic mice rapidly develop dramatic sympathetic neuritic dystrophy:
      a new experimental model of diabetic autonomic neuropathy.
AB  - To address the pathogenesis of diabetic autonomic neuropathy, we have examined
      the sympathetic nervous system in non-obese diabetic (NOD) and streptozotocin
      (STZ)-induced diabetic mice, two models of type 1 diabetes, and the db/db mouse,
      a model of type 2 diabetes. After only 3 to 5 weeks of diabetes, NOD mice
      developed markedly swollen axons and dendrites ("neuritic dystrophy") in the
      prevertebral superior mesenteric and celiac ganglia (SMG-CG), similar to the
      pathology described in diabetic STZ- and BBW-rat and man. Comparable changes
      failed to develop in the superior cervical ganglia of the NOD mouse or in the SMG
      CG of non-diabetic NOD siblings. STZ-induced diabetic mice develop identical
      changes, although at a much slower pace and to a lesser degree than NOD mice. NOD
      SCID mice, which are genetically identical to NOD mice except for the absence of
      T and B cells, do not develop diabetes or neuropathology comparable to diabetic
      NOD mice. However, STZ-treated NOD-SCID mice develop severe neuritic dystrophy,
      evidence against an exclusively autoimmune pathogenesis for autonomic neuropathy
      in this model. Chronically diabetic type 2 db/db mice fail to develop neuritic
      dystrophy, suggesting that hyperglycemia alone may not be the critical and
      sufficient element. The NOD mouse appears to be a valuable model of diabetic
      sympathetic autonomic neuropathy with unambiguous, rapidly developing
      neuropathology which corresponds closely to the characteristic pathology of other
      rodent models and man.

PMID- 14578207
TI  - Viable mouse models of acid beta-glucosidase deficiency: the defect in Gaucher
      disease.
AB  - Gaucher disease is an autosomal recessively inherited disease caused by mutations
      at the acid beta-glucosidase (GCase) locus (GBA). To develop viable models of
      Gaucher disease, point mutations (pmuts), encoding N370S, V394L, D409H, or D409V
      were introduced into the mouse GCase (gba) locus. DNA sequencing verified each
      unique pmut. Mutant GCase mRNAs were near wild-type (WT) levels. GCase activities
      were reduced to 2 to 25% of WT in liver, lung, spleen, and cultured fibroblasts
      from pmut/pmut or pmut/null mice. The corresponding brain GCase activities were
      approximately 25% of WT. N370S homozygosity was lethal in the neonatal period.
      For the other pmut mice, a few storage cells appeared in the spleen at > or =7
      months (D409H or D409V homozygotes) or > or =1 year (V394L homozygotes).
      V394L/null, D409H/null, or D409V/null mice showed scattered storage cells in
      spleen at approximately 3 to 4 months. Occasional storage cells (sinusoidal
      cells) were present in liver. In D409V/null mice, large numbers of Mac-3-positive
      storage cells (ie, macrophages) accumulated in the lung. Glycosphingolipid
      analyses showed varying rates of progressive glucosylceramide accumulation in
      visceral organs of pmut/pmut or pmut/null mice, but not in brain. These GCase
      deficient mice provide tools for gaining insight into the pathophysiology of
      Gaucher disease and developing improved therapies.

PMID- 14578208
TI  - A new model for inflammation-induced preterm birth: the role of platelet
      activating factor and Toll-like receptor-4.
AB  - Preterm birth is a leading cause of neonatal morbidity and mortality. Despite a
      growing body of evidence correlating inflammation with preterm birth, the signal
      transduction pathways responsible for the emptying of the uterus in the setting
      of intrauterine inflammation has not been elucidated. We now report a unique,
      reproducible mouse model of localized intrauterine inflammation. This model
      results in 100% preterm delivery with no maternal mortality. Using our model, we
      also show that platelet-activating factor is a crucial mediator of both
      inflammation-induced preterm birth and fetal demise. Using C3H/HeJ mice, we
      demonstrate that toll-like receptor-4 (TLR-4) plays a role in lipopolysaccharide
      induced preterm birth but not in inflammation-induced fetal death.
      Immunohistochemistry studies demonstrate the presence of the platelet-activating
      factor receptor in both endometrial glands and smooth muscle in uterine tissues.
      Molecular studies demonstrate the differential expression of platelet-activating
      factor receptor and TLR-4 in uterine and cervical tissue throughout gestation.
      Quantitative polymerase chain reaction revealed an up-regulation of TLR-4 in the
      fundal region of the uterus in response to intrauterine inflammation. The use of
      this model will increase our understanding of the significant clinical problem of
      inflammation-induced preterm birth and will elucidate signal transduction
      pathways involved in an inflammatory state.

PMID- 14578209
TI  - Progression to malignancy in the polyoma middle T oncoprotein mouse breast cancer
      model provides a reliable model for human diseases.
AB  - Animal models are powerful tools to analyze the mechanism of the induction of
      human breast cancer. Here we report a detailed analysis of mammary tumor
      progression in one mouse model of breast cancer caused by expression of the
      polyoma middle T oncoprotein (PyMT) in the mammary epithelium, and its comparison
      to human breast tumors. In PyMT mice, four distinctly identifiable stages of
      tumor progression from premalignant to malignant stages occur in a single primary
      tumor focus and this malignant transition is followed by a high frequency of
      distant metastasis. These stages are comparable to human breast diseases
      classified as benign or in situ proliferative lesions to invasive carcinomas. In
      addition to the morphological similarities with human breast cancer, the
      expression of biomarkers in PyMT-induced tumors is also consistent with those
      associated with poor outcome in humans. These include a loss of estrogen and
      progesterone receptors as well as integrin-beta1 expression and the persistent
      expression of ErbB2/Neu and cyclinD1 in PyMT-induced tumors as they progress to
      the malignant stage. An increased leukocytic infiltration was also closely
      associated with the malignant transition. This study demonstrates that the PyMT
      mouse model is an excellent one to understand the biology of tumor progression in
      humans.

PMID- 14578210
TI  - A golden hamster model for human acute Nipah virus infection.
AB  - A predominantly pig-to-human zoonotic infection caused by the novel Nipah virus
      emerged recently to cause severe morbidity and mortality in both animals and man.
      Human autopsy studies showed the pathogenesis to be related to systemic
      vasculitis that led to widespread thrombotic occlusion and microinfarction in
      most major organs especially in the central nervous system. There was also
      evidence of extravascular parenchymal infection, particularly near damaged
      vessels (Wong KT, Shieh WJ, Kumar S, Norain K, Abdullah W, Guarner J, Goldsmith
      CS, Chua KB, Lam SK, Tan CT, Goh KJ, Chong HT, Jusoh R, Rollin PE, Ksiazek TG,
      Zaki SR, Nipah Virus Pathology Working Group: Nipah virus infection: Pathology
      and pathogenesis of an emerging paramyxoviral zoonosis. Am J Pathol 2002,
      161:2153-2167). We describe here a golden hamster (Mesocricetus auratus) model
      that appears to reproduce the pathology and pathogenesis of acute human Nipah
      infection. Hamsters infected by intranasal or intraperitoneal routes died within
      9 to 29 days or 5 to 9 days, respectively. Pathological lesions were most severe
      and extensive in the hamster brain. Vasculitis, thrombosis, and more rarely,
      multinucleated endothelial syncytia, were found in blood vessels of multiple
      organs. Viral antigen and RNA were localized in both vascular and extravascular
      tissues including neurons, lung, kidney, and spleen, as demonstrated by
      immunohistochemistry and in situ hybridization, respectively. Paramyxoviral-type
      nucleocapsids were identified in neurons and in vessel walls. At the terminal
      stage of infection, virus and/or viral RNA could be recovered from most solid
      organs and urine, but not from serum. The golden hamster is proposed as a
      suitable model for further studies including pathogenesis studies, anti-viral
      drug testing, and vaccine development against acute Nipah infection.

PMID- 14578211
TI  - Altered epithelial cell proportions in the fetal lung of glucocorticoid receptor
      null mice.
AB  - Glucocorticoids provide important signals for maturation of the fetal lung and
      antenatal glucocorticoids are used to reduce the respiratory insufficiency
      suffered by preterm infants. To further understand the role of glucocorticoids in
      fetal lung maturation, we have analyzed mice with a targeted null mutation for
      the glucocorticoid receptor (GR) gene, which severely retards lung development.
      The lungs of fetal GR-null mice have increased lung weight and DNA content, are
      condensed and hypercellular, with reduced septal thinning leading to a 6-fold
      increase in the airway to capillary diffusion distance. In fetal GR-null mice,
      mRNA levels of the type II epithelial cell surfactant protein genes A and C were
      reduced by approximately 50%. Analysis of epithelial cell types by electron
      microscopy revealed that the proportions of type II cells were increased by
      approximately 30%, whereas the proportions of type-I cells were markedly reduced
      (by approximately 50%). Similarly, we found a 50% reduction in mRNA levels for
      T1alpha and aquaporin-5, two type I cell-specific markers, and a 20% reduction in
      aquaporin-1 mRNA levels. This demonstrates that during murine embryonic
      development, receptor-mediated glucocorticoid signaling facilitates the
      differentiation of epithelial cells into type I cells, but is not obligatory for
      type II cell differentiation.

PMID- 14578212
TI  - Monocyte recruitment into the lungs in pneumococcal pneumonia.
AB  - The recruitment of monocytes into the alveolar spaces is crucial for clearing
      infections and resolving the inflammatory response. We have previously reported
      the effect of acute pneumonia on monocyte transport through the bone marrow, and
      the present study concerns their clearance from the blood and migration into the
      lung airspaces. Dividing monocytes were labeled with the thymidine analog, 5'
      bromo-2'-deoxyuridine (BrdU). Whole blood containing the labeled monocytes
      (MO(BrdU)) was transfused from either donor rabbits with pneumonia or from
      uninfected controls into recipients with pneumonia, where they were detected in
      blood and tissues using a double immunostaining method. The results show that
      MO(BrdU) from infected animals rapidly disappeared from the circulation (P <
      0.05), preferentially sequestered in the infected lung tissue within 1 h (22.0 +/
      3.3% versus 6.0 +/- 0.4%, pneumonic region versus peripheral blood, P < 0.05),
      and accumulated to a greater degree in pneumonic airspaces than control monocytes
      48 h after transfusion (3.9 +/- 0.5% versus 1.1 +/- 0.1%, P < 0.05). We conclude
      that immature monocytes released from the marrow by pneumonia sequester rapidly
      in lung microvessels but their migration in pneumonic airspaces is delayed.

PMID- 14578213
TI  - Surfactant in newborn compared with adolescent pigs: adaptation to neonatal
      respiration.
AB  - Surfactant composition and function differ between vertebrates, depending on
      pulmonary anatomy and respiratory physiology. Because pulmonary development in
      pigs is similar to that in humans, we investigated surface tension function,
      composition of phospholipid molecular species, and concentrations of surfactant
      protein (SP)-A to -D in term newborn pigs (NP) compared with adolescent pigs
      (AP), using the pulsating bubble surfactometer, mass spectrometry, high
      performance liquid chromatography, and immunoblot techniques (IT). NP was more
      potent than AP surfactant in reaching minimal surface tension values near zero
      mN/m. Whereas SP-A and SP-D were comparable, SP-B and SP-C were increased 3- to 4
      fold in NP surfactant. Moreover, fluidizing phospholipids such as
      palmitoylmyristoyl-PC (PC16:0/14:0) and palmitoylpalmitoleoyl-PC (PC16:0/16:1)
      were increased at the expense of PC16:0/16:0 (32.4 +/- 0.6 versus 44.5 +/- 3.2%,
      respectively). Whereas concentrations of total anionic phospholipids were similar
      in NP and AP surfactant (9.9 +/- 0.3 and 12.0 +/- 0.3%, respectively),
      phosphatidylinositol was the predominant anionic phospholipid in NP surfactant.
      We conclude that, compared with AP, NP surfactant displays better surface tension
      function under dynamic conditions, which is associated with increased
      concentrations of SP-B and SP-C, as well as fluidizing phospholipids at the
      expense of PC16:0/16:0.

PMID- 14578214
TI  - Phosphoinositide 3-OH kinase inhibition prevents ventilation-induced lung cell
      activation.
AB  - In acute respiratory distress syndrome patients, protective ventilation
      strategies reduce mortality and proinflammatory mediator levels. It has been
      suggested that some of the side effects of mechanical ventilation are caused by
      the excessive release of mediators capable of causing pulmonary inflammation and
      tissue destruction (biotrauma). Selective inhibition of this process might be
      used to minimize the side effects of artificial mechanical ventilation. This
      study was designed to identify the cell types and specific signaling mechanisms
      that are activated by ventilation with increased pressure/volume
      (overventilation). In isolated perfused mouse lungs, overventilation caused
      nuclear translocation of nuclear factor-kappaB (NF-kappaB) and enhanced
      expression of interleukin-6 mRNA in alveolar macrophages and alveolar epithelial
      type II cells. The phosphoinositide 3-OH kinase inhibitor Ly294002 prevented
      nuclear translocation of NF-kappaB and the subsequent release of interleukin-6
      and macrophage inflammatory protein-2alpha in overventilated but not in endotoxic
      lungs. Similar results were obtained in rats in vivo, where Ly294002 prevented NF
      kappaB activation by overventilation but not by endotoxin. These findings show
      that alveolar macrophages and alveolar epithelial type II cells contribute to the
      ventilation-induced release of proinflammatory mediators and that selective
      inhibition of this process is possible without inhibiting the activation of NF
      kappaB by endotoxin.

PMID- 14578215
TI  - Leukotriene D4 activates alveolar epithelial Na,K-ATPase and increases alveolar
      fluid clearance.
AB  - Cysteinyl leukotrienes are increased during acute lung injury in animals and
      humans. In this study, we determined the effect of leukotriene D4 (LTD4) on the
      function of Na,K-ATPase in alveolar epithelial cells and on alveolar fluid
      clearance in rat lungs. LTD4 (1 x 10(-7) M) increased Na,K-ATPase activity at 1
      and 5 minutes by 14% (p < 0.05) and 31% (p < 0.001), respectively, in A549
      alveolar epithelial cells. This was accompanied by recruitment of Na,K-ATPase
      alpha1 subunits from intracellular compartment(s) to the basolateral plasma
      membrane. LTD4-induced alpha1 Na,K-ATPase membrane translocation was blocked by
      the dual cysteinyl LT1 (cysLT1)/ cysteinyl LT3 (cysLT3) receptor antagonist BAY
      u9773, but not by the cysLT1 antagonist MK571, implicating the cysLT3 receptor.
      Expression of mRNA for cysLT2, but not cysLT1, was confirmed in A549 cells and
      rat alveolar type 2 cells by reverse transcriptase-polymerase chain reaction.
      Finally, compared with control, LTD4 (1 x 10(-11) M) increased alveolar fluid
      clearance by 41% (p < 0.001) in isolated, perfused rat lungs; this was also
      blocked by BAY-u9773 but not MK571. By activating alveolar epithelial Na,K-ATPase
      and increasing alveolar fluid reabsorption, cysteinyl leukotrienes may, in part,
      have a beneficial role in the acute respiratory distress syndrome.

PMID- 14578216
TI  - A monoclonal antibody to alpha1beta1 blocks antigen-induced airway responses in
      sheep.
AB  - The integrin alpha1beta1 (very late antigen-1; CD49a/CD29) is a major adhesion
      receptor for collagen I, IV, and VI, and its induced expression on activated
      monocytes and lymphocytes plays a central role in their retention and activation
      at inflammatory sites in autoimmune pathologies. However, the role of alpha1beta1
      in allergic settings has not been explored. In this study, we show that a single
      45-mg dose of aerosolized monoclonal antibody AQC2 to the alpha1 chain of human
      and sheep very late antigen-1, given 30 minutes before challenge, blocks both the
      allergen-induced late response and the associated airway hyperresponsiveness,
      functional indicators of allergen-induced inflammation, in sheep. AQC2 does not
      affect the early response. Consistent with these effects, AQC2 tended to reduce
      the cell response associated with local antigen instillation. An isotype-matched
      control antibody had no protective effects. Two humanized versions of AQC2, a
      wild-type IgG1 and an aglycosyl form of the same monoclonal antibody, which has
      reduced Fc receptor-mediated effector functions, are equally effective in
      blocking the antigen-induced late response and airway hyperresponsiveness in the
      sheep model. These data suggest that mononuclear leukocyte adhesion-dependent
      pathologies contribute to allergic lung disease and provide proof-of-concept that
      antagonists of alpha1 integrins may be useful in preventing these events.

PMID- 14578217
TI  - Airway inflammation after cessation of exposure to agents causing occupational
      asthma.
AB  - Subjects with occupational asthma (OA) generally present asthma symptoms and
      airway hyperresponsiveness after cessation of exposure. We hypothesized that they
      are also left with airway inflammation. We assessed 133 subjects with OA at a
      mean interval of 8.7 years (0.5-20.8 years) after cessation of exposure by
      questionnaire, airway caliber, and responsiveness to methacholine. Satisfactory
      samples of induced sputum were obtained from 98 subjects. We defined three groups
      of subjects: (1) cured: normalization of the concentration of methacholine
      provoking a 20% decrease in FEV1 (PC20), (2) improved: increase in PC20 by 3.2
      fold or more but PC20 still abnormal, and (3) not improved: no significant change
      in PC20. In all, 9/28 subjects (32.1%) with no improvement versus 6/56 (10.7%)
      subjects with partial and complete improvements had sputum eosinophils equal to
      or greater than 2% and 11/28 (39.3%) subjects versus 11/56 (19.6%) subjects
      showed sputum neutrophils equal to or greater than 61%. Levels of interleukin-8
      and of the neutrophil-derived myeloperoxidase were significantly more elevated in
      sputum of subjects with no improvement. Those in the cured or improved groups had
      a significantly longer time lapse since diagnosis and a higher PC20 at the time
      of diagnosis. We conclude that failure to improve after cessation of exposure to
      an agent causing OA is associated with airway inflammation at follow-up.

PMID- 14578219
TI  - Insulin-like growth factor I and calcium balance: evolving concepts of an
      evolutionary process.

PMID- 14578218
TI  - Moxifloxacin-containing regimen greatly reduces time to culture conversion in
      murine tuberculosis.
AB  - Tuberculosis continues to be a major cause of morbidity and mortality in the
      world. The expansion of tuberculosis control programs has been limited by the
      lengthy and cumbersome nature of current chemotherapeutic regimens. A new drug
      that improves the sterilizing activity of current regimens would reduce the
      duration of therapy without sacrificing efficacy, thereby enhancing treatment
      completion rates and preserving precious public health resources. The new 8
      methoxyfluoroquinolone moxifloxacin has potent activity against both actively
      multiplying and nonactively multiplying tubercle bacilli. Using a murine model
      that is representative of chemotherapy for human tuberculosis, we show that the
      combination of moxifloxacin, rifampin, and pyrazinamide reduced the time needed
      to eradicate Mycobacterium tuberculosis from the lungs of infected mice by up to
      2 months when compared with the standard regimen of isoniazid, rifampin, and
      pyrazinamide. The findings suggest that this regimen has the potential to
      substantially shorten the duration of therapy needed to cure human tuberculosis.

PMID- 14578220
TI  - The brainstem is a key target for neuroendocrine research on obesity.

PMID- 14578221
TI  - Good versus evil: changing the approach to hormone replacement therapy.

PMID- 14578222
TI  - Galanin-like peptide functions more like leptin than like galanin.

PMID- 14578223
TI  - Individual differences in maternal care reveal the neural mechanisms of
      nurturance.

PMID- 14578224
TI  - Endocrine-related resources from the National Institutes of Health.

PMID- 14578225
TI  - National Hormone and Peptide Program, National Institute of Diabetes and
      Digestive and Kidney Diseases: Peptide hormones, subunits, antisera other
      reagents available.

PMID- 14578226
TI  - Effective exercise modality to reduce insulin resistance in women with type 2
      diabetes.
AB  - OBJECTIVE: The purpose of this study was to evaluate whether a combined
      resistance and aerobic training program would improve insulin sensitivity
      compared with aerobic training alone in postmenopausal women with type 2
      diabetes. A second objective was to relate the improved insulin sensitivity to
      changes in abdominal adipose tissue (AT) and thigh muscle density. RESEARCH
      DESIGN AND METHODS: A total of 28 obese postmenopausal women with type 2 diabetes
      were randomly assigned to one of three 16-week treatments: control, aerobic only
      training (Ae only), or aerobic plus resistance training (Ae+RT). Pre- and
      posttreatment outcome measures included glucose disposal by hyperinsulinemic
      euglycemic clamp and computed tomography scans of abdominal AT and mid-thigh
      skeletal muscle. RESULTS: Glucose infusion rates increased significantly (P <
      0.05) in the Ae+RT group. Both exercise groups had reduced abdominal subcutaneous
      and visceral AT and increased muscle density. The Ae+RT training group exhibited
      a significantly greater increase in muscle density than the Ae only group.
      Improved glucose disposal was independently associated with changes in
      subcutaneous AT, visceral AT, and muscle density. Muscle density retained a
      relationship with glucose disposal after controlling for abdominal AT.
      CONCLUSIONS: Adding resistance training to aerobic training enhanced glucose
      disposal in postmenopausal women with type 2 diabetes. The improved insulin
      sensitivity is related to loss of abdominal subcutaneous and visceral AT and to
      increased muscle density.

PMID- 14578227
TI  - Use of thiazolidinediones and risk of heart failure in people with type 2
      diabetes: a retrospective cohort study.
AB  - OBJECTIVE: To compare the incidence of heart failure in individuals with type 2
      diabetes receiving thiazolidinediones (TZDs) versus other oral antihyperglycemic
      agents. RESEARCH DESIGN AND METHODS: We conducted a retrospective cohort study
      using a health insurance claims database. The study sample included patients with
      type 2 diabetes who received an oral antihyperglycemic agent between January 1995
      and March 2001. Those with any claims for TZDs were designated "exposed," and
      each was compared with five randomly selected unexposed patients. Those with
      diagnoses of heart failure or who received digoxin or a diuretic in the year
      before their index date were excluded. The primary measure of interest was
      incidence of heart failure, which was defined as a hospitalization or outpatient
      visit with a diagnosis of heart failure. RESULTS: TZD patients (n = 5441) were
      younger than control subjects (n = 28103) but more likely to have coronary artery
      disease or diabetes complications, receive ACE inhibitors, beta-blockers,
      metformin, or insulin, and have undergone HbA(1c) tests or eye exams; they also
      had more comorbidities and higher costs (all P < 0.05). However, TZD use was
      predictive of heart failure even after controlling for these variables (hazard
      ratio = 1.7, P < 0.001). Adjusted incidence of heart failure at 40 months was
      8.2% for TZD patients and 5.3% for control subjects. CONCLUSIONS: The results of
      this observational study suggest that TZDs may increase the risk of heart
      failure. Physicians should use TZDs with caution in patients with heart failure,
      remain vigilant for manifestations of heart failure in those receiving these
      drugs (especially patients with cardiovasculopathy), and consider alternate
      therapies for patients who develop symptoms of heart failure, such as shortness
      of breath.

PMID- 14578228
TI  - French multicentric survey of outcome of pregnancy in women with pregestational
      diabetes.
AB  - OBJECTIVE: To evaluate perinatal outcome in pregnancies in women with type 1 and
      type 2 diabetes and the influence of preconception care 10 years after the St.
      Vincent's declaration. RESEARCH DESIGN AND METHODS: A cross-sectional study was
      conducted in 12 perinatal centers in France in 2000-2001. The main investigated
      outcomes were perinatal mortality, major congenital malformations, and preterm
      delivery. RESULTS: Among 435 single pregnancies, 289 (66.4%) were from women with
      type 1 and 146 (33.6%) from women with type 2 diabetes. Perinatal mortality rate
      was 4.4% (0.7% national rate), severe congenital malformations rate was 4.1%
      (2.2% national rate), and preterm delivery rate was 38.2% (4.7% national rate).
      Preconception care was provided in 48.5% women with type 1 diabetes and in 24.0%
      women with type 2 diabetes. Women whose first trimester HbA(1c) was >8% had
      higher rates of perinatal mortality (9.2 vs. 2.5%; odds ratio 3.9; 95% CI 1.5
      9.7; P < 0.005), major congenital malformations (8.3 vs. 2.5%; 3.5; 1.3-8.9; P <
      0.01), and preterm delivery (57.6 vs. 24.8%; 1.4; 1.1-1.7; P < 0.005) than those
      with first trimester HbA(1c) <8%. These results are similar to those reported in
      France in 1986-1988. CONCLUSIONS: Pregnancies in women with diabetes are still
      poorly planned and complicated by higher rates of perinatal mortality and major
      congenital malformations. Despite knowledge of the importance of intensified
      glycemic control before pregnancy, reaching the St. Vincent's target needs
      further implementation in France.

PMID- 14578229
TI  - Cigarette smoking and the risk of gestational and pregestational diabetes in two
      consecutive pregnancies.
AB  - OBJECTIVE: Cigarette smoking during pregnancy may increase the risk of
      gestational diabetes mellitus (GDM) or pregestational diabetes mellitus (PDM).
      Smoking has been associated positively with hyperinsulinemia and insulin
      resistance in experimental studies, although the association with diabetes
      remains unclear. To further explore this issue, we examined the association with
      smoking in the largest prospective cohort study of GDM and PDM to date. RESEARCH
      DESIGN AND METHODS: The study population comprised 212190 women in the population
      based Swedish Birth Registry who had their first and second deliveries between
      January 1987 and December 1995. Maternal characteristics were recorded in a
      standardized manner at the first prenatal visit, followed by a clinical
      examination and a standardized in-person interview to assess lifestyle habits.
      Women were categorized as nonsmokers, light smokers (one to nine cigarettes per
      day), or moderate-to-heavy smokers (at least 10 cigarettes per day). RESULTS:
      Women with GDM in their first pregnancy experienced an eight- to ninefold
      increased risk of GDM or PDM in their second pregnancy. Cigarette smoking was not
      associated with increased risk of these conditions. Neither women who smoked
      during their first and second pregnancies nor those who commenced smoking between
      pregnancies had a higher risk of GDM or PDM than nonsmokers. CONCLUSIONS: Our
      findings do not support an association between cigarette smoking and risk of GDM
      or PDM in young women of childbearing age.

PMID- 14578230
TI  - Complications in young adults with early-onset type 2 diabetes: losing the
      relative protection of youth.
AB  - OBJECTIVE: To determine whether adults diagnosed with type 2 diabetes from age 18
      to 44 years more aggressively develop clinical complications after diagnosis than
      adults diagnosed at >or=45 years of age. RESEARCH DESIGN AND METHODS: We compared
      outcomes among 7844 adults in a health maintenance organization who were newly
      diagnosed with type 2 diabetes between 1996 and 1998. We abstracted clinical data
      from electronic medical, laboratory, and pharmacy records. To adjust for length
      of follow-up and sex, we used proportional hazards models to compare incident
      complication rates through 2001 between onset groups (mean follow-up 3.9 years).
      To adjust for the increasing prevalence of macrovascular disease with advancing
      age, onset groups were matched by age and sex to control subjects without
      diabetes for macrovascular outcomes. RESULTS: Adults with early-onset type 2
      diabetes were 80% more likely to begin insulin therapy than those with usual
      onset type 2 diabetes (hazards ratio [HR] 1.8, 95% CI 1.5-2.0), despite a similar
      average time to requiring insulin ( approximately 2.2 years). Although the
      combined risk of microvascular complications did not differ overall,
      microalbuminuria was more likely in early-onset type 2 diabetes than usual-onset
      type 2 diabetes (HR 1.2, 95% CI 1.1-1.4). The hazard of any macrovascular
      complication in early-onset type 2 diabetic patients compared with control
      subjects was twice as high in usual-onset type 2 diabetic patients compared with
      control subjects (HR 7.9 vs. 3.8, respectively). Myocardial infarction (MI) was
      the most common macrovascular complication, and the hazard of developing an MI in
      early-onset type 2 diabetic patients was 14-fold higher than in control subjects
      (HR 14.0, 95% CI 6.2-31.4). In contrast, adults with usual-onset type 2 diabetes
      had less than four times the risk of developing an MI compared with control
      subjects (HR 3.7, P < 0.001). CONCLUSIONS: Early-onset type 2 diabetes appears to
      be a more aggressive disease from a cardiovascular standpoint. Although the
      absolute rate of cardiovascular disease (CVD) is higher in older adults, young
      adults with early-onset type 2 diabetes have a much higher risk of CVD relative
      to age-matched control subjects.

PMID- 14578231
TI  - Pathways of infant and childhood growth that lead to type 2 diabetes.
AB  - OBJECTIVE: Although a link between small body size at birth and later type 2
      diabetes has been repeatedly documented, less is known about the associations
      between the disease and growth during infancy. The aim of this study was to
      explore the pathways of infant and early growth that lead to type 2 diabetes in
      adult life. RESEARCH DESIGN AND METHODS: We carried out a longitudinal study of
      8760 subjects born in Helsinki from 1934 to 1944. On average, they had 8
      measurements of height and weight between birth and 1 year of age and another 10
      measurements between 1 and 12 years of age. We identified people with type 2
      diabetes using a national register. RESULTS: Among babies whose birth weights
      were <or=3.5 kg, the rate of infant growth was unrelated to later type 2
      diabetes. Among babies with birth weights >3.5 kg, slow growth in length between
      birth and 3 months of age predicted later disease. Rapid gain in BMI after age 2
      years increased the risk of later disease in both groups of babies, but this
      effect was greatest among children who had slow growth in length between birth
      and 3 months of age. In children whose Z-scores for length decreased, an SD
      increase in BMI at age 12 years was associated with an odds ratio (OR) for type 2
      diabetes of 1.77 (95% CI 1.50-2.09). The corresponding OR in subjects whose Z
      scores for length increased was 1.42 (95% CI 1.20-1.69). Rapid gain in childhood
      BMI was associated with high maternal BMI and socioeconomic factors (fewer people
      in the home and lower social class). CONCLUSIONS: Babies with above-average birth
      weights may develop type 2 diabetes later in life if poor living conditions lead
      to faltering growth in length in the first few months after birth. We speculate
      that growth faltering at this time is associated with lifelong impairment of
      insulin metabolism and inability to meet the challenge of rapid childhood
      increase in BMI.

PMID- 14578232
TI  - HBsAg carrier status and the association between gestational diabetes with
      increased serum ferritin concentration in Chinese women.
AB  - OBJECTIVE: To determine whether the high prevalence of hepatitis B surface
      antigen (HBsAg) carriage in our population can explain the previous observation
      of an association between increased maternal serum ferritin concentration and
      gestational diabetes in Hong Kong Chinese women. RESEARCH DESIGN AND METHODS: A
      retrospective study was performed on 767 nonanemic women with singleton pregnancy
      who had iron status assessed at 28-30 weeks. The result of the routine antenatal
      HBsAg screening was retrieved from patient records. The HBsAg-positive and 
      negative groups were compared for maternal characteristics, prevalence of
      gestational diabetes in the third trimester, prevalence of high serum ferritin
      and iron concentrations, and transferrin saturation, which is defined as a value
      in the highest quartile established by the measurements obtained from the HBsAg
      negative group. RESULTS: The incidences of oral glucose tolerance test and
      gestational diabetes were significantly increased in the HBsAg-positive group.
      The HBsAg-positive women with gestational diabetes had significantly increased
      prevalence of high serum ferritin compared with the HBsAg-negative women,
      irrespective of the latter's gestational diabetes status. Multiple logistic
      regression analysis confirmed the independent association between HBsAg carrier
      status with gestational diabetes (relative risk 3.51, 95% CI 1.83-6.73) but
      excluded high ferritin as an independent factor. CONCLUSIONS: Our results
      indicate that maternal HBsAg carriage could explain in part the association
      between increased serum ferritin concentration with gestational diabetes in Hong
      Kong Chinese women, and that HBsAg carrier status is an independent risk factor
      for gestational diabetes.

PMID- 14578233
TI  - Applying diabetes-related Prevention Quality Indicators to a national cohort of
      veterans with diabetes.
AB  - OBJECTIVE: The Prevention Quality Indicators (PQIs) are measures of
      hospitalizations that reflect quality of ambulatory care. We applied the PQIs of
      metabolic decompensation to Veterans Health Administration (VHA) utilizers with
      diabetes. We identified patient-level characteristics associated with
      hospitalization for metabolic decompensation, developed a risk-adjustment model
      for the measures, and compared regional network performance using these PQIs.
      RESEARCH DESIGN AND METHODS: This was a retrospective cohort study of 406575
      veterans with diabetes who used the VHA between 1997 and 1999. The outcomes were
      the PQIs of uncontrolled diabetes, short-term complications, or a combined
      measure. Patient-level variables were identified from administrative databases.
      Variation in performance of the networks was compared between full risk
      adjustment and age and sex adjustment only. RESULTS: In fiscal year 1999, there
      were 1719 VHA discharges (4.2 per 1000 cohort members) for uncontrolled and short
      term complications of diabetes. A logistic regression model including age, sex,
      marital status, Charlson Comorbidity Index, mental health condition, insulin use,
      and oral antiglycemic medication use was developed for risk adjustment of the
      combined PQI. Full risk adjustment changed performance ranks of the networks
      using the combined PQI outcome relative to age and sex adjustment only. Ten
      networks remained in the same quartile of performance, five moved one quartile,
      and seven moved two or more quartiles. CONCLUSIONS: The PQIs of uncontrolled and
      short-term complications of diabetes are uncommon outcomes among veterans with
      diabetes and should be used only as a combined outcome. More complete risk
      adjustment should be used when comparing systems of care using the combined
      measure.

PMID- 14578234
TI  - The Singapore impaired glucose tolerance follow-up study: does the ticking clock
      go backward as well as forward?
AB  - OBJECTIVE: To 1). document the change in glucose tolerance for subjects with
      normal glucose tolerance (NGT) and impaired glucose tolerance (IGT) over time,
      2). identify baseline factors associated with worsening of glucose tolerance, and
      3). determine whether cardiovascular disease (CVD) risk factors associated with
      IGT improved in tandem with glucose tolerance. RESEARCH DESIGN: Subjects with IGT
      and NGT (matched for age, sex, and ethnic group) were identified from a cross
      sectional survey conducted in 1992. Subjects with IGT (297) and NGT (298) (65.0%)
      were reexamined in 2000. Glucose tolerance (assessed by 75-g oral glucose
      tolerance test), anthropometric data, serum lipids, blood pressure, and insulin
      resistance were determined at baseline and at the follow-up examination. RESULTS:
      For NGT subjects, 14.0% progressed to IGT and 4.3% to diabetes over 8 years. For
      IGT subjects, 41.4% reverted to NGT, 23.0% remained impaired glucose tolerant,
      and 35.1% developed diabetes. Obesity, hypertriglyceridemia, higher blood
      pressure, increased insulin resistance, and lower HDL cholesterol at baseline
      were associated with worsening of glucose tolerance in both IGT and NGT subjects.
      Those with IGT who reverted to NGT remained more obese and had higher blood
      pressure than those with NGT in both 1992 and 2000. However, serum triglyceride,
      HDL cholesterol, and insulin resistance values in 2000 became indistinguishable
      from those of subjects who maintained NGT throughout the study period.
      CONCLUSIONS: Some, but not all, CVD risk factors associated with IGT and with the
      risk of future diabetes normalize when glucose tolerance normalizes. Continued
      surveillance and treatment in subjects with IGT, even after they revert to NGT,
      may be important in the prevention of CVD.

PMID- 14578235
TI  - High prevalence of diabetes in Adana, a southern province of Turkey.
AB  - OBJECTIVE: To determine the prevalence of diabetes and glucose intolerance and
      their relationship with risk factors in Adana, a southern province of Turkey,
      where risk factors are more prominent, probably because of social and economic
      reasons. RESEARCH DESIGN AND METHODS: The study population included 1637 randomly
      selected adults aged 20-79 years. Diagnosis of diabetes was based on plasma
      glucose values using the 1999 diagnostic criteria recommended by the World Health
      Organization. RESULTS: The crude prevalence of diabetes was 12.9% in men and
      10.9% in women (P = 0.207). Total prevalence of diabetes was 11.6%. The screening
      process identified previously undiagnosed diabetes in 4.2% of individuals and
      impaired glucose homeostasis (consisting of impaired glucose tolerance and
      impaired fasting glucose) in an additional 4.3% of subjects. The prevalence of
      hypertension was 26.4% among men and 36.6% among women (P < 0.0001). Total
      prevalence of hypertension was 32.9%, and prevalence of obesity was 43.4%. Age,
      sex, BMI, waist circumference, hypertension, family history of diabetes, and
      triglycerides were independently associated with diabetes. CONCLUSIONS: The
      prevalence of diabetes in Adana is higher than expected in both urban and rural
      areas. Obesity and hypertension also seem to be common metabolic disorders in
      this area. Age, hypertension, obesity, high triglyceride level, and family
      history of diabetes are independently associated with diabetes. Therefore,
      primary prevention through lifestyle modifications may have a critical role in
      the control of diabetes.

PMID- 14578236
TI  - Influence of autonomic nervous system dysfunction on the development of type 2
      diabetes: the CARDIA study.
AB  - OBJECTIVE: We investigated whether autonomic nervous system dysfunction,
      estimated by slow heart rate recovery (HRR) following cessation of an exercise
      treadmill test, was associated with increases in insulin and glucose over time
      and the development of type 2 diabetes. RESEARCH DESIGN AND METHODS: Maximal
      exercise tests were performed by 3295 healthy adults aged 18-30 years in the
      Coronary Artery Risk Development in Young Adults (CARDIA) study. Repeat
      measurements of insulin and glucose collected at 7-, 10-, and 15-year
      examinations were compared by quartiles of HRR (maximum heart rate minus heart
      rate 2 min after cessation of the test). Incident diabetes was identified at any
      follow-up examination as glucose >or=7 mmol/l or the use of diabetes control
      medication. RESULTS: Among participants who did not develop diabetes, fasting
      insulin concentrations increased from baseline to year 15. Following adjustment
      (for age, race, sex, smoking status, and BMI), participants with the slowest HRR
      (quartile 1) had higher fasting insulin at each examination than participants
      with faster HRR (e.g., year 15 examination: 88.1 vs. 81.3 pmol/l for quartile 1
      vs. quartile 4, respectively, P = 0.05). Glucose did not differ by quartile of
      HRR at any examination. Among participants with poor fitness, the risk of
      developing diabetes (n = 98) was 3.4-fold greater (95% CI 1.5-8.0) when HRR was
      <42 vs. >42 bpm. This persisted following adjustment for baseline insulin.
      CONCLUSIONS: Autonomic dysfunction, in combination with poor physical fitness,
      may be a mechanism associated with early glucose dysmetabolism and the
      development of diabetes.

PMID- 14578237
TI  - The relationship between provider coordination and diabetes-related foot
      outcomes.
AB  - OBJECTIVE: To investigate the relationship between provider coordination and
      amputations in patients with diabetes. RESEARCH DESIGN AND METHODS: The study
      design was a cross-sectional, descriptive study of process and outcomes for
      diabetes-related foot care at 10 Department of Veterans Affairs (VA) medical
      centers representing different geographic regions, population densities, patient
      populations, and amputation rates. The subjects included all providers of
      diabetes foot care and a random sample of primary care providers at each medical
      center. The main outcome measures were the Foot Systems Assessment Tool
      (FootSAT), nontraumatic lower extremity amputation rates, and investigators'
      ordinal ranking of site effectiveness based on site visits. RESULTS: The survey
      response rate was 48%. Scale reliability, as measured by Cronbach's alpha, ranged
      from 0.73 to 0.93. The scale scores for programming coordination (i.e.,
      electronic medical record, policies, reminders, protocols, and educational
      seminars) and feedback coordination (i.e., discharge planning, quality of care
      meetings, and curbside consultations) were negatively associated with amputation
      rates, suggesting centers with higher levels of coordination had lower amputation
      rates. Statistically significant associations were found for programming
      coordination with minor amputations (P = 0.02) and total amputations (P = 0.04).
      CONCLUSIONS: The FootSAT demonstrated a stronger association with amputation
      rates than site visit rankings. Among these 10 VA facilities, those with higher
      levels of programming and feedback coordination had significantly lower
      amputation rates.

PMID- 14578238
TI  - Integrating medical management with diabetes self-management training: a
      randomized control trial of the Diabetes Outpatient Intensive Treatment program.
AB  - OBJECTIVE: This study evaluated the Diabetes Outpatient Intensive Treatment
      (DOIT) program, a multiday group education and skills training experience
      combined with daily medical management, followed by case management over 6
      months. Using a randomized control design, the study explored how DOIT affected
      glycemic control and self-care behaviors over a short term. The impact of two
      additional factors on clinical outcomes were also examined (frequency of case
      management contacts and whether or not insulin was started during the program).
      RESEARCH DESIGN AND METHODS: Patients with type 1 and type 2 diabetes in poor
      glycemic control (A1c >8.5%) were randomly assigned to DOIT or a second
      condition, entitled EDUPOST, which was standard diabetes care with the addition
      of quarterly educational mailings. A total of 167 patients (78 EDUPOST, 89 DOIT)
      completed all baseline measures, including A1c and a questionnaire assessing
      diabetes-related self-care behaviors. At 6 months, 117 patients (52 EDUPOST, 65
      DOIT) returned to complete a follow-up A1c and the identical self-care
      questionnaire. RESULTS: At follow-up, DOIT evidenced a significantly greater drop
      in A1c than EDUPOST. DOIT patients also reported significantly more frequent
      blood glucose monitoring and greater attention to carbohydrate and fat contents
      (ACFC) of food compared with EDUPOST patients. An increase in ACFC over the 6
      month period was associated with improved glycemic control among DOIT patients.
      Also, the frequency of nurse case manager follow-up contacts was positively
      linked to better A1c outcomes. The addition of insulin did not appear to be a
      significant contributor to glycemic change. CONCLUSIONS: DOIT appears to be
      effective in promoting better diabetes care and positively influencing glycemia
      and diabetes-related self-care behaviors. However, it demands significant time,
      commitment, and careful coordination with many health care professionals. The
      role of the nurse case manager in providing ongoing follow-up contact seems
      important.

PMID- 14578239
TI  - Inconsistent use of diabetes medications, diabetes complications, and mortality
      in older mexican americans over a 7-year period: data from the Hispanic
      established population for the epidemiologic study of the elderly.
AB  - OBJECTIVE: The aim of this study was to examine the relationship between
      inconsistency in use of diabetes drugs and risk of renal, eye, and circulation
      problems and death over a 7-year period in community-dwelling older Mexican
      Americans. RESEARCH DESIGN AND METHODS: Data are from the four waves of the
      Hispanic Established Population for the Epidemiologic Study of the Elderly. In
      home interviewers assessed consistency in use of diabetes medications among 908
      diabetic Mexican Americans, aged >or=65 years. Diabetes and complications were by
      self-report. Subjects with poor consistency in use of medication were those who,
      at any time during the 7-year follow-up, discontinued or inconsistently used
      their diabetes medications and those who had no diabetic medications at home
      despite self-report of taking medicine for diabetes. RESULTS: Thirty-six percent
      of our sample were inconsistent with diabetes medication usage. Older age and
      lack of supplemental health insurance were significantly associated with
      inconsistency of use of medication. In a multivariate logistic regression model,
      subjects with poor consistency in use of medication were more likely to report
      kidney problems (odds ratio [OR] 1.59; 95% CI 1.13-2.23; P = 0.008) at follow-up
      compared with those with good consistency, after controlling for age, sex,
      medication type, duration of diabetes, education, income, marital status,
      language of interview, insurance status, cognitive function, presence of
      depressive symptoms, activities of daily living, and instrumental activities of
      daily living. In Cox regression models, poor consistency with diabetic medication
      was also associated with increased all-cause mortality (hazard ratio [HR] 1.43;
      95% CI 1.13-1.82; P = 0.003) and diabetes-related deaths (1.66; 1.20-2.30; P =
      0.002) over a 7-year period after adjusting for relevant confounders.
      CONCLUSIONS: Inconsistent use of diabetic medication was associated with an
      increased risk of kidney problems and deaths over a 7-year period in older
      Mexican Americans.

PMID- 14578240
TI  - Controlled trial of a multifaceted intervention for improving quality of care for
      rural patients with type 2 diabetes.
AB  - OBJECTIVE: Despite good evidence and clinical practice guidelines, studies
      document that treatment of type 2 diabetes is less than optimal. Lack of
      resources or limited access may put patients in rural communities at particular
      risk for suboptimal care. RESEARCH DESIGN AND METHODS: We conducted a
      prospective, before/after study with concurrent controls to assess the
      effectiveness of a multidisciplinary diabetes outreach service (intervention) for
      improving the quality of care for rural patients with type 2 diabetes. Our
      intervention consisted of six monthly visits by a traveling team of specialist
      physicians, nurses, dieticians, and a pharmacist. The core of this service was
      specialist-to-rural primary care physician academic group detailing. Two
      comparable regions in Northern Alberta were randomly allocated to control or
      intervention. Data were collected before and 6 months after intervention in a
      representative volunteer sample. The primary outcome was a 10% improvement in any
      one of the following: blood pressure, total cholesterol, or HbA(1c). RESULTS: Our
      analysis included 200 intervention and 179 control subjects; 14 subjects were at
      all three primary outcome targets at baseline. The intervention was associated
      with a trend toward improvement in primary outcome at 6 months (44% intervention
      vs. 37% control; odds ratio 1.32, 95% CI 0.87-1.99). The intervention was
      associated with a significant improvement in blood pressure (42% intervention vs.
      25% control, P = 0.004); however, there were only small, nonsignificant changes
      in cholesterol or HbA(1c). The intervention was associated with a significant
      increase in satisfaction with diabetes care. Multivariate adjustment for baseline
      differences between intervention and control subjects did not affect any of the
      main results. CONCLUSIONS: A diabetes outreach service has the potential to
      improve the quality of diabetes care for rural patients. Future studies need to
      involve longer timelines and larger sample sizes.

PMID- 14578241
TI  - General quality of life in youth with type 1 diabetes: relationship to patient
      management and diabetes-specific family conflict.
AB  - OBJECTIVE: To evaluate self-report and parent proxy report of child/teen general
      quality of life in youth with type 1 diabetes, compare their responses with those
      of a general pediatric population, and identify relationships between diabetes
      management, diabetes-related family behavior, and diabetes-specific family
      conflict with quality of life in youth with type 1 diabetes. RESEARCH DESIGN AND
      METHODS: Study participants included 100 children, 8-17 years of age (12.1 +/-
      2.3), with type 1 diabetes for 0.5-6 years (2.7 +/- 1.6). Each child and a parent
      completed the Pediatric Quality of Life Inventory (PedsQL), completed the
      Diabetes Family Conflict Scale, and provided data on parent involvement in
      diabetes management. An independent measure of adherence to treatment assessed by
      the patient's clinician and a measure of glycemic control (HbA(1c)) were also
      collected. RESULTS: PedsQL responses from youth with type 1 diabetes were stable
      over 1 year and similar to norms from a healthy standardization sample for all
      three scales of the PedsQL: total, physical, and psychosocial quality of life.
      After controlling for age, duration of diabetes, sex, HbA(1c), and family
      involvement, child report of diabetes-specific family conflict (P < 0.01) was the
      only significant predictor of child report of quality of life (model R(2) = 0.21,
      P < 0.02). CONCLUSIONS: Youth with type 1 diabetes report remarkably similar
      quality of life to a nondiabetic youth population. Greater endorsement of
      diabetes-specific family conflict predicted diminished quality of life for the
      child. As treatment programs focus on intensifying glycemic control in youth with
      type 1 diabetes, interventions should include efforts to reduce diabetes-specific
      family conflict in order to preserve the child's overall quality of life.

PMID- 14578242
TI  - Pramlintide reduces postprandial glucose excursions when added to regular insulin
      or insulin lispro in subjects with type 1 diabetes: a dose-timing study.
AB  - OBJECTIVE: To assess the postprandial glucose-lowering effect of the human amylin
      analog pramlintide when given with either regular insulin or insulin lispro in
      subjects with type 1 diabetes, with an emphasis on the optimal dose timing
      relative to meals. RESEARCH DESIGN AND METHODS: In this randomized, single-blind,
      placebo-controlled, five-way crossover study, 19 subjects with type 1 diabetes
      using regular insulin and 21 subjects with type 1 diabetes using insulin lispro
      underwent five consecutive mixed meal tests. In randomized order, subjects
      received subcutaneous injections of placebo at -15 min or 60 microg pramlintide
      at -15, 0, +15, or +30 min relative to the meal after an overnight fast. Regular
      insulin or insulin lispro was injected at -30 and 0 min, respectively, at doses
      that were adjusted appropriately for both the content of the standardized meal
      and the anticipated effects of pramlintide. Plasma glucose concentrations were
      measured before and during the 4-h postmeal period. RESULTS: In both the regular
      insulin and insulin lispro groups, pramlintide injections at all four time points
      lowered the postprandial glucose excursion (36 to >100% reduction in incremental
      area under the concentration time curve from 0 to 4 h (AUC(0-4 h)) compared with
      placebo. However, only preprandial injections of pramlintide (-15 and 0 min) were
      able to prevent the initial postprandial surge in glucose. The optimal time for
      pramlintide injection was 0 min, which reduced the postprandial glucose excursion
      by >100% compared with regular insulin plus placebo (incremental AUC(0-4 h): -0.6
      +/- 2.5 vs. 11.0 +/- 2.9 mmolx h(-1) x l(-1), P < 0.0007) and by 75% compared
      with insulin lispro plus placebo (incremental AUC(0-4 h): 2.5 +/- 2.1 vs. 10.0 +/
      2.5 mmol x h(-1) x l(-1), P < 0.0098). No serious adverse events were reported.
      CONCLUSIONS: Pramlintide, given at or just before a meal, reduces the
      postprandial glucose excursion in subjects with type 1 diabetes, regardless of
      whether added to regular insulin or a rapid-acting insulin analog.

PMID- 14578243
TI  - The treat-to-target trial: randomized addition of glargine or human NPH insulin
      to oral therapy of type 2 diabetic patients.
AB  - OBJECTIVE: To compare the abilities and associated hypoglycemia risks of insulin
      glargine and human NPH insulin added to oral therapy of type 2 diabetes to
      achieve 7% HbA(1c). RESEARCH DESIGN AND METHODS: In a randomized, open-label,
      parallel, 24-week multicenter trial, 756 overweight men and women with inadequate
      glycemic control (HbA(1c) >7.5%) on one or two oral agents continued prestudy
      oral agents and received bedtime glargine or NPH once daily, titrated using a
      simple algorithm seeking a target fasting plasma glucose (FPG) <or=100 mg/dl (5.5
      mmol/l). Outcome measures were FPG, HbA(1c), hypoglycemia, and percentage of
      patients reaching HbA(1c) <or=7% without documented nocturnal hypoglycemia.
      RESULTS: Mean FPG at end point was similar with glargine and NPH (117 vs. 120
      mg/dl [6.5 vs. 6.7 mmol/l]), as was HbA(1c) (6.96 vs. 6.97%). A majority of
      patients ( approximately 60%) attained HbA(1c) <or=7% with each insulin type.
      However, nearly 25% more patients attained this without documented nocturnal
      hypoglycemia (<or=72 mg/dl [4.0 mmol/l]) with glargine (33.2 vs. 26.7%, P <
      0.05). Moreover, rates of other categories of symptomatic hypoglycemia were 21
      48% lower with glargine. CONCLUSIONS: Systematically titrating bedtime basal
      insulin added to oral therapy can safely achieve 7% HbA(1c) in a majority of
      overweight patients with type 2 diabetes with HbA(1c) between 7.5 and 10.0% on
      oral agents alone. In doing this, glargine causes significantly less nocturnal
      hypoglycemia than NPH, thus reducing a leading barrier to initiating insulin.
      This simple regimen may facilitate earlier and effective insulin use in routine
      medical practice, improving achievement of recommended standards of diabetes
      care.

PMID- 14578244
TI  - Insulin detemir is characterized by a consistent pharmacokinetic profile across
      age-groups in children, adolescents, and adults with type 1 diabetes.
AB  - OBJECTIVE: This trial aimed to characterize for the first time the
      pharmacokinetic profile of insulin detemir, the novel soluble basal insulin
      analog, in children and adolescents compared with adults. Comparisons were also
      made with NPH insulin to determine any between-treatment difference in the effect
      of age on pharmacokinetic profile. RESEARCH DESIGN AND METHODS: This single
      center, open-label, randomized, crossover trial included children (aged 6-12
      years, n = 13), adolescents (aged 13-17 years, n = 10), and adults (aged 18-65
      years, n = 11) of both sexes. Subjects were given single doses of 0.5 units/kg
      s.c. insulin detemir or 0.5 IU/kg NPH insulin on 2 separate days. Serial blood
      sampling was performed for 24 h for analysis of serum insulin detemir, human
      insulin, and glucose concentrations. RESULTS: The mean pharmacokinetic profile of
      insulin detemir was similar across all three age-groups. This was determined by
      statistical analyses of the data, which showed no overall age effect or between
      group differences when pairwise comparisons were made between children (or
      adolescents) and adults on the parameters of the area under the curve (AUC), AUC
      from zero to infinity, AUC from 0 to 24 h [AUC((0-24 h))], and the maximum
      concentration measured during the 24 h after closing. No overall age effect for
      AUC((0-24 h)) and C(max) was detected for NPH insulin, but data were only
      analyzable from seven adults and pairwise comparisons did indicate that children
      and adults had different pharmacokinetic profiles. Less total variability in the
      pharmacokinetics of insulin detemir than NPH insulin was indicated by lower
      coefficients of variation in AUC, C(max), and time to maximum concentration in
      all three age-groups. CONCLUSIONS: The data suggest that insulin detemir can be
      used in children and adolescents with type 1 diabetes using titration guidelines
      similar to those used in adults. Moreover, insulin detemir may offer the
      advantage of greater predictability of response in comparison to NPH insulin due
      to lower total variability and a lesser degree of kinetic disparity across age
      groups.

PMID- 14578245
TI  - Archimedes: a trial-validated model of diabetes.
AB  - OBJECTIVE: To build a mathematical model of the anatomy, pathophysiology, tests,
      treatments, and outcomes pertaining to diabetes that could be applied to a wide
      variety of clinical and administrative problems and that could be validated.
      RESEARCH DESIGN AND METHODS: We used an object-oriented approach, differential
      equations, and a construct we call "features." The level of detail and realism
      was determined by what clinicians considered important, by the need to
      distinguish clinically relevant variables, and by the level of detail used in the
      conduct of clinical trials. RESULTS: The model includes the pertinent organ
      systems, more than 50 continuously interacting biological variables, and the
      major symptoms, tests, treatments, and outcomes. The level of detail corresponds
      to that found in general medical textbooks, patient charts, clinical practice
      guidelines, and designs of clinical trials. The model is continuous in time and
      represents biological variables continuously. As demonstrated in a companion
      article, the equations can simulate a variety of clinical trials and reproduce
      their results with good accuracy. CONCLUSIONS: It is possible to build a
      mathematical model that replicates the pathophysiology of diabetes at a high
      level of biological and clinical detail and that can be tested by simulating
      clinical trials.

PMID- 14578246
TI  - Validation of the archimedes diabetes model.
AB  - OBJECTIVE: To validate the Archimedes model of diabetes and its complications for
      a variety of populations, organ systems, treatments, and outcomes. RESEARCH
      DESIGN AND METHODS: We simulated a variety of randomized controlled trials by
      repeating in the model the steps taken for the real trials and comparing the
      results calculated by the model with the results of the trial. Eighteen trials
      were chosen by an independent advisory committee. Half the trials had been used
      to help build the model ("internal" or "dependent" validations); the other half
      had not. Those trials comprise "external" or "independent" validations. RESULTS:
      A total of 74 validation exercises were conducted involving different treatments
      and outcomes in the 18 trials. For 71 of the 74 exercises there were no
      statistically significant differences between the results calculated by the model
      and the results observed in the trial. Considering only the trials that were
      never used to help build the model-the independent or external validations-the
      correlation was r = 0.99. Including all of the exercises, the correlation between
      the outcomes calculated by the model and the outcomes seen in the trials was r =
      0.99. When the absolute differences in outcomes between the control and treatment
      groups were compared, the correlation coefficient was r = 0.97. CONCLUSIONS: The
      Archimedes diabetes model is a realistic representation of the anatomy,
      pathophysiology, treatments, and outcomes pertinent to diabetes and its
      complications for applications that involve the populations, treatments,
      outcomes, and health care settings spanned by the trials.

PMID- 14578247
TI  - Association of the p22phox component of NAD(P)H oxidase with susceptibility to
      diabetic nephropathy in patients with type 1 diabetes.
AB  - OBJECTIVE: Increased production of reactive oxygen species (ROS) in diabetes is
      thought to play a major role in the pathogenesis of diabetic microvascular
      complications such as nephropathy and retinopathy. The NAD(P)H oxidase complex is
      an important source of ROS in the vasculature. The p22 subunit is polymorphic
      with a C242T variant that changes histidine-72 for a tyrosine in the potential
      heme binding site, together with a A640G in the 3' untranslated region. The aim
      was to investigate the frequency of these polymorphisms in 268 patients with type
      1 diabetes with or without microvascular complications. RESEARCH DESIGN AND
      METHODS: There was a highly significant increase in the frequency of the T/T242
      genotype in patients with nephropathy compared with those with retinopathy alone
      or no microvascular disease after 20 years' diabetes duration (uncomplicated) or
      normal healthy control subjects (33.3 vs. 6.5, 5.7, and 0.0%, respectively, P <
      0.000001). Furthermore, the T242/G640 haplotype was found in 39.4% of the
      patients with nephropathy but in only 26.5% of the patients with retinopathy and
      15.3 and 10.6% of the uncomplicated and normal control subjects, respectively.
      RESULTS: When these variants of NAD(P)H oxidase were analyzed together with
      aldose reductase (5'ALR2) susceptibility genotypes, >46.0% of the patients with
      nephropathy possessed a T242 allele with the Z-2 5'ALR2 allele compared with only
      11.2% of the uncomplicated patients (P < 0.00003). CONCLUSIONS: In conclusion,
      these results suggest NAD(P)H oxidase together with the polyol pathway may
      contribute to the pathogenesis of diabetic nephropathy.

PMID- 14578248
TI  - Prevalence of delayed gastric emptying in diabetic patients and relationship to
      dyspeptic symptoms: a prospective study in unselected diabetic patients.
AB  - OBJECTIVE: Data on the prevalence of abnormal gastric emptying in diabetic
      patients are still lacking. The relation between gastric emptying and dyspeptic
      symptoms assessed during gastric emptying measurement has not yet been
      investigated. The aim was to investigate the prevalence of delayed gastric
      emptying in a large cohort of unselected diabetic patients and to investigate the
      relation between gastric emptying and gastrointestinal sensations experienced in
      the 2 weeks before and during the test meal, prospectively. RESEARCH DESIGN AND
      METHODS: Gastric emptying was evaluated in 186 patients (106 with type 1
      diabetes, mean duration of diabetes 11.6 +/- 11.3 years) using 100 mg (13)C
      enriched octanoic acid added to a solid meal. RESULTS: Gastric emptying was
      significantly slower in the diabetic subjects than in the healthy volunteers
      (T(50): 99.5 +/- 35.4 vs. 76.8 +/- 21.4 min, P < 0.003; Ret(120 min): 30.6 +/-
      17.2 vs. 20.4 +/- 9.7%, P < 0.006). Delayed gastric emptying was observed in 51
      (28%) diabetic subjects. The sensations experienced in the 2 weeks before the
      test were weakly correlated with the sensation scored during the gastric emptying
      test. Sensations assessed during the gastric emptying test did predict gastric
      emptying to some extent (r = 0.46, P < 0.0001), whereas sensations experienced in
      the previous 2 weeks did not. CONCLUSIONS: This prospective study shows that
      delayed gastric emptying can be observed in 28% of unselected patients with
      diabetes. Upper gastrointestinal sensations scored during the gastric emptying
      tests do predict the rate of gastric emptying to some extent and sensation
      experienced during daily life does not.

PMID- 14578249
TI  - Semiquantitative analysis of the histopathological features of the neuropathic
      foot ulcer: effects of pressure relief.
AB  - OBJECTIVE: This study was designed to evaluate the histopathology of neuropathic
      ulcers and whether pressure relief could change such histological patterns.
      RESEARCH DESIGN AND METHODS: We compared neuropathic plantar ulcers tissue
      excised from 10 diabetic patients (group A) with those taken from 10 patients
      with comparable lesions and glycemic control after 20 days in a total contact
      cast (group B). Tissue specimens were blindly examined by two independent
      pathologists for hyperkeratosis, fibrosis, cutaneous annexes, capillaries,
      inflammation, cellular debris, and granulating tissue. For each parameter,
      quantification was obtained according to an arbitrary score: 0, absent; 1,
      present in <33%; 2, present in 34-66%; and 3, present in >67% of the lesion.
      RESULTS: Patients in group B showed a marked reduction in ulcer size after 20
      days of casting (P < 0.01). The histopathological features of the two groups
      markedly differed. Group A patients showed a predominance of inflammatory
      elements as well as matrix alterations, vessel disruptions, inflammation, and
      debris. Group B ulcers showed a shift toward a reparative pattern with prevalence
      of neoformed capillaries and fibroblasts. Semiquantitative analysis confirmed the
      prevalence of hyperkeratosis, fibrosis, inflammation, and cellular debris in
      group A patients (P < 0.05), whereas cutaneous annexes, capillaries, and
      granulating tissue were more prevalent in group B lesions (P < 0.01).
      CONCLUSIONS: These results indicate that pressure relief with a total contact
      cast is associated with changes in the histology of neuropathic foot ulcers,
      indicating reduction of inflammatory and reactive components and acceleration of
      reparative processes.

PMID- 14578250
TI  - Effects of stress hyperglycemia on acute myocardial infarction: role of
      inflammatory immune process in functional cardiac outcome.
AB  - OBJECTIVE: Stress hyperglycemia has been associated with increased mortality in
      patients with myocardial infarction (MI). We examined the association between
      plasma glucose levels, circulating inflammatory markers, T-cell activation, and
      functional cardiac outcome in patients with first MI. RESEARCH DESIGN AND
      METHODS: Echocardiographic parameters, circulating levels of interleukin-18 (IL
      18), C-reactive protein (CPR), and the percent of CD16-CD56, CD4/CD8, CD152, and
      HLA-DR expression were investigated in 108 patients with acute MI on admission to
      the emergency ward. RESULTS: Our review found that 31 new hyperglycemic patients
      (glycemia >or=7 mmol/l) had higher infarct segment length (P < 0.05) and
      myocardial performance index (P < 0.02) and reduced transmitral Doppler flow (P <
      0.05), pulmonary flow analysis (P < 0.02), and ejection fraction (P < 0.05)
      compared with 36 hyperglycemic diabetic patients and 41 normoglycemic patients.
      Plasma IL-18 and CRP were higher in the hyperglycemic than in the normoglycemic
      patients (P < 0.005), with the highest values in patients with new hyperglycemia
      (P < 0.05). Hyperglycemic patients had a higher percent of CD16+/CD56+ cells and
      CD4/CD8 ratio (P < 0.01), whereas they had lower CD152 expression (which has a
      negative regulatory function in T-cell activation) compared with normoglycemic
      patients (P < 0.001). CONCLUSIONS: During MI, hyperglycemia is associated with
      increased levels of inflammatory markers, enhanced expression of cytotoxic T
      cells, and reduced expression of T-cells, which are implicated in limiting the
      immune process. An increased inflammatory immune process seems a likely mechanism
      linking acute hyperglycemia to poor cardiac outcome in MI patients.

PMID- 14578251
TI  - Symptoms of common maternal infections in pregnancy and risk of islet
      autoimmunity in early childhood.
AB  - OBJECTIVE: The aim of this study was to test whether symptoms of maternal
      infections during pregnancy and indicators of postnatal infections predict
      development of islet autoimmunity in children at genetically increased risk of
      type 1 diabetes. RESEARCH DESIGN AND METHODS: A total of 871 children with type 1
      diabetes-associated HLA genotypes born in Denver, Colorado, and 391 siblings or
      offspring of individuals with type 1 diabetes referred from clinics in the Denver
      metropolitan area were enrolled soon after birth and seen in the clinic at age
      <or=15 months. Information on indicators of infection was collected by structured
      interviews soon after birth and at ages 3-15 months. Clinic visits were scheduled
      at ages 9, 15, and 24 months, and yearly thereafter. The outcome was positivity
      for one or more islet autoantibodies (to GAD(65), insulin, or IA-2/ICA512) at two
      or more consecutive visits. During a mean follow-up of 4.2 years, 52 children
      developed islet autoimmunity. RESULTS: Children whose mother reported at least
      one symptom of infection during pregnancy (mostly respiratory or
      gastrointestinal) had a significantly lower risk of islet autoimmunity compared
      with other children (hazard ratio 0.48; 95% CI 0.27-0.83). After stratification,
      the association appeared among girls (0.21; 0.09-0.48) but not among boys (1.09;
      0.47-2.51) with a P value for interaction of 0.005. Symptoms of neonatal
      infections, early daycare attendance, exposure to cats or dogs, and household
      crowding were not related to islet autoimmunity. CONCLUSIONS: Symptoms of
      maternal infections in pregnancy predicted a significantly lower risk of islet
      autoimmunity in young girls, suggesting a protective effect of such infections.

PMID- 14578252
TI  - Sex differences in the prognostic importance of diabetes in patients with
      ischemic heart disease undergoing coronary angiography.
AB  - OBJECTIVE: Women with ischemic heart disease have poorer outcomes than men and
      are suggested to have greater risk associated with diabetes. We evaluated the
      prognosis associated with diabetes, in analyses stratified by sex, to determine
      whether similar differences are seen in a large unselected cohort of patients.
      RESEARCH DESIGN AND METHODS: Using the Alberta Provincial Project for Outcomes
      Assessment in Coronary Heart Disease (APPROACH), a clinical data collection and
      follow-up initiative capturing all patients undergoing cardiac catheterization in
      Alberta, Canada, the relative significance of diabetes on long-term survival in
      13152 men and 4249 women was evaluated in patients presenting with or without
      myocardial infarction and according to first treatment received. RESULTS: The 1
      year mortality rates were 4.7% and 6.8% in men and women (P < 0.001), 4.1% and
      7.4% in nondiabetic and diabetic men (P < 0.001), and 5.8% and 9.6% in
      nondiabetic and diabetic women, respectively (P < 0.001). The risk-adjusted Cox
      proportional hazard ratios associated with diabetes in myocardial infarction were
      1.03 in men and 1.20 in women. The diabetes hazard ratios for percutaneous
      coronary intervention were 1.28 in men and 1.40 in women, 1.23 in men and 1.32 in
      women for bypass surgery, and 1.26 in men and 1.31 in women for medical therapy
      (P = NS for all diabetes hazard ratio comparisons between men and women).
      CONCLUSIONS: Hazard ratios quantifying the adverse prognosis associated with
      diabetes in patients undergoing angiography are consistently higher among women
      than men, but the differences across sexes are not statistically significant.
      These slight sex differences noted in the APPROACH registry are similar to
      previously reported findings and may be clinically important.

PMID- 14578253
TI  - Effects of pioglitazone versus diet and exercise on metabolic health and fat
      distribution in upper body obesity.
AB  - OBJECTIVE: Insulin resistance is associated with visceral adiposity, and
      interventions that reduce this depot, e.g., diet and exercise, improve insulin
      resistance. Thiazolidinediones (TZDs) also improve insulin action but
      paradoxically increase total fat mass, perhaps through remodeling (recruitment of
      smaller fat cells) and redistribution of adipose tissue. We assessed the effects
      of pioglitazone versus diet and exercise on fat distribution and the relationship
      between fat distribution and insulin sensitivity in upper body obesity. RESEARCH
      DESIGN AND METHODS: Thirty-nine upper body obese, insulin-resistant, nondiabetic
      men and premenopausal women were randomly assigned to receive either 30 mg/day
      pioglitazone or a diet and exercise program for 20 weeks. Before and after the
      intervention, insulin sensitivity, body composition, body fat distribution (waist
      to-hip ratio [WHR], computed tomography abdomen, and dual-energy X-ray
      absorptiometry), and abdominal and femoral fat cell size were assessed. RESULTS:
      Diet and exercise resulted in an 11.8 +/- 1.1 kg weight loss. Both diet and
      exercise and pioglitazone improved insulin sensitivity, but only the former was
      associated with loss of intra-abdominal fat. Pioglitazone increased total body
      fat, which preferentially accumulated in the lower body depot in both men and
      women. WHRs decreased in both groups. Abdominal fat cell size decreased (P =
      0.06) after diet and exercise. No statistically significant changes in fat cell
      size were observed in pioglitazone-treated volunteers. CONCLUSIONS: In
      nondiabetic upper body obese subjects, increasing insulin sensitivity via diet
      and exercise accompanies reductions in visceral fat. Pioglitazone treatment also
      improves insulin sensitivity and lowers WHR, but this is due to a selective
      increase in lower body fat. This confirms a site-specific responsiveness of
      adipose tissue to TZD and suggests that improvements in insulin sensitivity by
      pioglitazone are achieved independent of changes in intra-abdominal fat.

PMID- 14578254
TI  - The metabolic syndrome as predictor of type 2 diabetes: the San Antonio heart
      study.
AB  - OBJECTIVE: The oral glucose tolerance test identifies high-risk subjects for
      diabetes, but it is costly and inconvenient. To find better predictors of type 2
      diabetes, we evaluated two different definitions of the metabolic syndrome
      because insulin resistance, which is commonly associated with this clustering of
      metabolic factors, frequently precedes the onset of type 2 diabetes. RESEARCH
      DESIGN AND METHODS: We compared the ability of the National Cholesterol Education
      Program (NCEP) definition, a modified version of the 1999 World Health
      Organization (WHO) definition that excludes the 2-h glucose requirement, and
      impaired glucose tolerance (IGT) to predict incident type 2 diabetes. In the San
      Antonio Heart Study, 1734 participants completed a 7- to 8-year follow-up
      examination. RESULTS: IGT and the NCEP definition had higher sensitivity than the
      modified WHO definition (51.9, 52.8, and 42.8%, respectively). IGT had a higher
      positive predictive value than the NCEP and modified WHO definitions (43.0, 30.8,
      and 30.4%, respectively). The combination of the IGT and NCEP definitions
      increased the sensitivity to 70.8% with an acceptable positive predictive value
      of 29.7%. Risk for incidence of type 2 diabetes using the NCEP definition was
      independent of other risk factors, including IGT and fasting insulin (odds ratio
      3.30, 95% CI 2.27-4.80). The NCEP definition performed better with fasting
      glucose >or=5.4 mmol/l (sensitivity 62.0% and positive predictive value 30.9%).
      CONCLUSIONS: The metabolic syndrome predicts diabetes independently of other
      factors. However, the NCEP definition performs better than the modified 1999 WHO
      definition. Lowering the fasting glucose cutoff to 5.4 mmol/l improves the
      prediction of diabetes by the metabolic syndrome.

PMID- 14578256
TI  - Dealing with complexity in clinical diabetes: the value of archimedes.

PMID- 14578255
TI  - Follow-up report on the diagnosis of diabetes mellitus.

PMID- 14578257
TI  - Prevention of obesity and diabetes.

PMID- 14578258
TI  - Metabolic syndrome/insulin resistance syndrome/pre-diabetes: new section in
      diabetes care.

PMID- 14578259
TI  - The coming of age of the metabolic syndrome.

PMID- 14578260
TI  - Diabetes modeling.

PMID- 14578261
TI  - Is treatment of insulin resistance beneficial independent of glycemia?

PMID- 14578262
TI  - Screening for adrenal antibodies in children with type 1 diabetes and autoimmune
      thyroid disease.

PMID- 14578263
TI  - Predictive value of autoantibodies to IA-2 for insulin requirements in Japanese
      subjects with type 1 diabetes.

PMID- 14578264
TI  - Prognostic value of the carotid artery intima-media thickness for the presence
      and severity of coronary artery disease in type 2 diabetic patients.

PMID- 14578265
TI  - Test strips for blood glucose monitors are not always accurate.

PMID- 14578266
TI  - Sirolimus-induced interstitial pneumonitis in an islet transplant recipient.

PMID- 14578267
TI  - No deterioration in glycemic control in HNF-1alpha maturity-onset diabetes of the
      young following transfer from long-term insulin to sulphonylureas.

PMID- 14578268
TI  - Type 1 diabetes and multiple sclerosis: together at last.

PMID- 14578269
TI  - Serum amylase and lipase in diabetic ketoacidosis.

PMID- 14578270
TI  - Rosiglitazone lowers blood pressure and increases arterial compliance in
      postmenopausal women with type 2 diabetes.

PMID- 14578271
TI  - Deficiency in the detection of microalbuminuria by urinary dipstick in diabetic
      patients.

PMID- 14578272
TI  - Type 2 diabetes and the Naaman syndrome.

PMID- 14578273
TI  - Extreme altitude mountaineering and type 1 diabetes: the Cho Oyu alpinisti in
      Alta Quota expedition.

PMID- 14578274
TI  - Acute angle closure glaucoma following rapid correction of hyperglycemia.

PMID- 14578275
TI  - Prevalence of the metabolic syndrome in middle-aged men and women.

PMID- 14578276
TI  - Clinical worth of adiponectin levels in obesity and glycemic control of Japanese
      type 2 diabetic patients.

PMID- 14578277
TI  - Amputation and mortality in new-onset diabetic foot ulcers stratified by
      etiology: response to Moulik, Mtonga, and Gill.

PMID- 14578278
TI  - Patients on atypical antipsychotic drugs: another high-risk group for type 2
      diabetes: response to Lean and Pajonk.

PMID- 14578281
TI  - Identification of a beta-cell-specific HLA class I restricted epitope in type 1
      diabetes.
AB  - Type 1 diabetes is an autoimmune disease in which pancreatic beta-cells are
      destroyed by cytotoxic T-cells that recognize peptide epitopes presented by HLA
      class I molecules. The identification of human beta-cell epitopes may
      significantly improve the prospects for immunodiagnosis and immunotherapy in type
      1 diabetes. Using algorithms to predict nonameric beta-cell peptides that would
      bind to the common HLA allele, HLA-A*0201, we identified a potential epitope from
      the leader sequence of islet amyloid polypeptide (human islet amyloid polypeptide
      [IAPP] precursor protein [preproIAPP] 5-13: KLQVFLIVL). Peripheral blood
      mononuclear cells (PBMCs) were isolated from 18 HLA-A*0201 patients with type 1
      diabetes (9 with recent-onset [<180 days; range, 1-120 days] and 9 with long
      standing diabetes [>180 days; range, 183-3,273 days]) and 9 healthy, nondiabetic
      control subjects. PBMCs were screened for peptide recognition using interferon
      gamma enzyme-linked immunospot (ELISpot) assays. Of the nine patients with recent
      onset type 1 diabetes, six had ELISpot responses to preproIAPP 5-13 that were >3
      SDs above the mean of the nondiabetic control subjects (P = 0.002). In contrast,
      no patients with type 1 diabetes for >180 days had a response above this
      threshold. In summary, preproIAPP 5-13 is a novel HLA class I epitope recognized
      by a significant proportion of cytotoxic T-cells from HLA-A*0201 patients with
      recent-onset type 1 diabetes and may prove to be a useful tool for the prediction
      and/or prevention of this disease.

PMID- 14578282
TI  - Hypothesis: shifting the equilibrium from activity to food leads to autonomic
      unbalance and the metabolic syndrome.

PMID- 14578283
TI  - Increased insulin sensitivity and hypoinsulinemia in APS knockout mice.
AB  - A tyrosine kinase adaptor protein containing pleckstrin homology and SH2 domains
      (APS) is rapidly and strongly tyrosine phosphorylated by insulin receptor kinase
      upon insulin stimulation. The function of APS in insulin signaling has heretofore
      remained unknown. APS-deficient (APS(-/-)) mice were used to investigate its
      function in vivo. The blood glucose-lowering effect of insulin, as assessed by
      the intraperitoneal insulin tolerance test, was increased in APS(-/-) mice.
      Plasma insulin levels during fasting and in the intraperitoneal glucose tolerance
      test were lower in APS(-/-) mice. APS(-/-) mice showed an increase in the whole
      body glucose infusion rate as assessed by the hyperinsulinemic-euglycemic clamp
      test. These findings indicated that APS(-/-) mice exhibited increased sensitivity
      to insulin. However, overexpression of wild-type or dominant-negative APS in
      3T3L1 adipocytes did not affect insulin receptor numbers, phosphorylations of
      insulin receptor, insulin receptor substrate-1, or Akt and mitogen-activated
      protein kinase. The glucose uptake and GLUT4 translocation were not affected by
      insulin stimulation in these cells. Nevertheless, the insulin-stimulated glucose
      transport in isolated adipocytes of APS(-/-) mice was increased over that of
      APS(+/+) mice. APS(-/-) mice also showed increased serum levels of leptin and
      adiponectin, which might explain the increased insulin sensitivity of adipocytes.

PMID- 14578284
TI  - Coordinated upregulation of oxidative pathways and downregulation of lipid
      biosynthesis underlie obesity resistance in perilipin knockout mice: a microarray
      gene expression profile.
AB  - Obesity is a major risk factor for diabetes and heart disease. We previously
      reported that the inactivation of the gene for perilipin (plin), an adipocyte
      lipid droplet surface protein, produced lean and obesity-resistant mice. To
      dissect the underlying mechanisms involved, we used oligonucleotide microarrays
      to analyze the gene-expression profile of white adipose tissue (WAT), liver,
      heart, skeletal muscle, and kidney of plin(-/-) and plin(+/+) mice. As compared
      with wild-type littermates, the WAT of plin(-/-) mice had 270 and 543 transcripts
      that were significantly up- or downregulated. There was a coordinated
      upregulation of genes involved in beta-oxidation, the Krebs cycle, and the
      electron transport chain concomitant with a downregulation of genes involved in
      lipid biosynthesis. There was also a significant downregulation of the stearoyl
      CoA desaturase-1 gene, which has been associated with obesity resistance. Thus,
      in response to the constitutive activation of lipolysis associated with absence
      of perilipin, WAT activated pathways to rid itself of the products of lipolysis
      and activated pathways of energy expenditure that contribute to the observed
      obesity resistance. The biochemical pathways involved in obesity resistance in
      plin(-/-) mice identified in this study may represent potential targets for the
      treatment of obesity.

PMID- 14578285
TI  - Transgenic neuronal expression of proopiomelanocortin attenuates hyperphagic
      response to fasting and reverses metabolic impairments in leptin-deficient obese
      mice.
AB  - Hypothalamic proopiomelanocortin (POMC) gene expression is reduced in many forms
      of obesity and diabetes, particularly in those attributable to deficiencies in
      leptin or its receptor. To assess the functional significance of POMC in
      mediating metabolic phenotypes associated with leptin deficiency, leptin
      deficient mice bearing a transgene expressing the POMC gene under control of the
      neuron-specific enolase promoter were produced. The POMC transgene attenuated
      fasting-induced hyperphagia in wild-type mice. Furthermore, the POMC transgene
      partially reversed obesity, hyperphagia, and hypothermia and effectively
      normalized hyperglycemia, glucosuria, glucose intolerance, and insulin resistance
      in leptin-deficient mice. Effects of the POMC transgene on glucose homeostasis
      were independent of the partial correction of hyperphagia and obesity.
      Furthermore, the POMC transgene normalized the profile of hepatic and adipose
      gene expression associated with gluconeogenesis, glucose output, and insulin
      sensitivity. These results indicate that central POMC is a key modulator of
      glucose homeostasis and that agonists of POMC products may provide effective
      therapy in treating impairments in glucose homeostasis when hypothalamic POMC
      expression is reduced, as occurs with leptin deficiency, hypothalamic damage, and
      aging.

PMID- 14578286
TI  - Learned meal initiation attenuates the anorexic effects of the melanocortin
      agonist MTII.
AB  - The central melanocortin system is critically involved in the control of food
      intake and body weight. Administration of melanocortin agonists reduces food
      intake and adiposity, and the central melanocortin system is demonstrated to
      mediate the anorexic effects of both leptin and insulin. An important unanswered
      question has been whether melanocortin agonists would also reduce food intake
      that is driven by factors other than homeostatic mechanisms (e.g., conditioned
      eating). In the first experiment, we identified that long-term maintenance on a
      meal-feeding schedule attenuated rats' sensitivity to central administration of
      the melanocortin agonist MTII. The results from a second experiment demonstrate
      that the attenuation of the MTII-induced anorexia was due to learned schedules of
      food intake rather than food deprivation per se. Results from the final
      experiment suggest that this attenuation of MTII-induced anorexia may be
      independent of the decreased sensitivity caused by a high-fat diet. These results
      support the hypothesis that meal-feeding schedules can lead to anticipatory
      physiological responses that attenuate the anorexic effects of exogenous
      melanocortin agonists.

PMID- 14578287
TI  - Recombinant Fabs of human monoclonal antibodies specific to the middle epitope of
      GAD65 inhibit type 1 diabetes-specific GAD65Abs.
AB  - Autoantibodies to the 65-kDa isoform of GAD (GAD65Abs) are associated with type 1
      diabetes development, but the conformational nature of the GAD65Ab epitopes
      complicates the evaluation of disease risk. Six GAD65-specific recombinant Fabs
      (rFabs) were cloned from monoclonal antibodies b96.11, DP-C, DP-A, DPD, 144, and
      221-442. The binding of GAD65Abs in 61 type 1 diabetic patients to GAD65 was
      analyzed by competitive radioimmunoassays with the six rFabs to ascertain disease
      specific GAD65Ab binding specificities. The median binding was reduced
      significantly by rFab b96.11 (72%) (P < 0.0001), DP-A (84%) (P < 0.0001), DP-C
      (84%) (P < 0.0001), 221-442 (79%) (P < 0.0001), and DP-D (80%) (P < 0.0001). The
      competition pattern in type 1 diabetic patients differed from that in GAD65Ab
      positive late autoimmune diabetes in adults (LADA) patients (n = 44), first
      degree relatives (n = 38), and healthy individuals (n = 14). Whereas 87 and 72%
      of the type 1 diabetic sera were competed by rFab b96.11 and DP-C, respectively,
      only 34 and 26% of LADA patients, 18 and 25% of first-degree relatives, and 7 and
      28% of healthy individuals showed competition (P < 0.0001). These findings
      support the view that type 1 diabetes is associated with disease- and epitope
      specific GAD65Abs and supports the notion that the middle epitope is disease
      associated. These GAD65-specific rFabs should prove useful in predicting type 1
      diabetes and in the study of conformational GAD65Ab epitopes.

PMID- 14578288
TI  - Target cell expression of suppressor of cytokine signaling-1 prevents diabetes in
      the NOD mouse.
AB  - Although lymphocyte infiltration and islet destruction are hallmarks of diabetes,
      the mechanisms of beta-cell destruction are not fully understood. One issue that
      remains unresolved is whether cytokines play a direct role in beta-cell death. We
      investigated whether beta-cell cytokine signaling contributes to autoimmune type
      1 diabetes. We demonstrated that NOD mice harboring beta-cells expressing the
      suppressor of cytokine signaling-1 (SOCS-1), an inhibitor of Janus kinase/signal
      transducers and activators of transcription (JAK/STAT) signaling, have a markedly
      reduced incidence of diabetes. Similar to their non-transgenic (Tg) littermates,
      SOCS-1-Tg mice develop insulitis and their splenocytes transfer disease to
      NODscid recipients. Disease protection correlates with suppression of cytokine
      induced STAT-1 phosphorylation in SOCS-1-expressing beta-cells and with a reduced
      sensitivity of these cells to destruction by diabetogenic cells in vivo.
      Interestingly, lymphocytes recruited to the pancreas of SOCS-1-Tg mice
      transferred diabetes to NODscid recipients with a reduced efficiency, suggesting
      that the pancreatic environment in SOCS-1-Tg mice does not support the
      maintenance of functionally differentiated T-cells. These results suggest that
      cytokines contribute to the development of type 1 diabetes by acting directly on
      the target beta-cell. Importantly, given that the SOCS-1-expressing mouse
      maintain normal blood glucose levels throughout life, this study also showed that
      SOCS-1 expression by beta-cells can represent a promising strategy to prevent
      type 1 diabetes.

PMID- 14578289
TI  - Discovery of gene networks regulating cytokine-induced dysfunction and apoptosis
      in insulin-producing INS-1 cells.
AB  - Locally released cytokines contribute to beta-cell dysfunction and apoptosis in
      type 1 diabetes. In vitro exposure of insulin-producing INS-1E cells to the
      cytokines interleukin (IL)-1beta + interferon (IFN)-gamma leads to a significant
      increase in apoptosis. To characterize the genetic networks implicated in beta
      cell dysfunction and apoptosis and its dependence on nitric oxide (NO)
      production, we performed a time-course microarray analysis of cytokine-induced
      genes in insulin-producing INS-1E cells. INS-1E cells were exposed in duplicate
      to IL-1beta + IFN-gamma for six different time points (1, 2, 4, 8, 12, and 24 h)
      with or without the inducible NO synthase (iNOS) blocker N(G)-monomethyl-L
      arginine (NMA). The microarray analysis identified 698 genes as cytokine modified
      (>or=2.5-fold change compared with control) in at least one time point. Based on
      their temporal pattern of variation, the cytokine-regulated genes were classified
      into 15 clusters by the k-means method. These genes were further classified into
      14 different groups according to their putative function. Changes in the
      expression of genes related to metabolism, signal transduction, and transcription
      factors at all time points studied indicate beta-cell attempts to adapt to the
      effects of continuous cytokine exposure. Notably, several apoptosis-related genes
      were modified at early time points (2-4 h) preceding iNOS expression. On the
      other hand, 46% of the genes modified by cytokines after 8-24 h were NO
      dependent, indicating the important role of this radical for the late effects of
      cytokines. The present results increase by more than twofold the number of known
      cytokine-modified genes in insulin-producing cells and yield comprehensive
      information on the role of NO for these modifications in gene expression. These
      data provide novel and detailed insights into the gene networks activated in beta
      cells facing a prolonged immune assault.

PMID- 14578290
TI  - Parathyroid hormone-related protein induces insulin expression through activation
      of MAP kinase-specific phosphatase-1 that dephosphorylates c-Jun NH2-terminal
      kinase in pancreatic beta-cells.
AB  - Parathyroid hormone-related protein (PTHrP) increases the content and mRNA level
      of insulin in a mouse beta-cell line, MIN6, and primary-cultured mouse islets. We
      examined the mechanism of PTHrP-induced insulin expression. The PTHrP effect was
      markedly augmented by SB203580, a mitogen-activated protein (MAP) kinase
      inhibitor, and SB203580 itself increased insulin expression extensively, even
      without PTHrP. Because SB203580 inhibits both p38 and c-jun NH(2)-terminal
      kinases (JNKs), we investigated the JNK-specific inhibitor SP600125. SP600125
      also increased insulin content and its mRNA level. PTHrP induced
      dephosphorylation of JNK1/2, and PTHrP-induced insulin expression was blocked by
      a dominant-negative type JNK-APF. We suspected that dual specificity MAP kinase
      phosphatases (MKPs) may be involved in the PTHrP-induced insulin expression by
      inactivating JNK1/2. MIN6 cells contained at least five MKPs, among which only
      MKP-1 was inducible by PTHrP. PTHrP-induced insulin expression was blocked by the
      MKP-1 expression inhibitor Ro-31-8220, indicating that the PTHrP effect is
      mediated by MKP-1. Indeed, adenoviral MKP-1 expression increased insulin
      expression by decreasing a phosphorylation form of JNKs and a resulting
      phosphorylated form of c-jun in MIN6 cells. The phosphorylated form of c-jun is
      known to repress cAMP-dependent insulin gene promoter activity. Thus, MKP-1
      controls the insulin expression by downregulating a JNK/c-jun pathway.

PMID- 14578291
TI  - Rapamycin has a deleterious effect on MIN-6 cells and rat and human islets.
AB  - Rapamycin (sirolimus) is a macrolide fungicide with immunosuppressant properties
      that is used in human islet transplantation. Little is known about the effects of
      rapamycin on MIN-6 cells and islets. Rapamycin had a dose-dependent, time
      dependent, and glucose-independent deleterious effect on MIN-6 cell viability. At
      day 1, using the MTT method, 0.01 nmol/l rapamycin reduced cell viability to 83
      +/- 6% of control (P < 0.05). Using the calcein AM method, at day 2, 10 nmol/l
      rapamycin caused a reduction in cell viability to 73 +/- 5% of control (P <
      0.001). Furthermore, 10 and 100 nmol/l rapamycin caused apoptosis in MIN-6 cells
      as assessed by the transferase-mediated dUTP nick-end labeling assay. Compared
      with control, there was a 3.1 +/- 0.6-fold increase (P < 0.01) in apoptosis in
      MIN-6 cells treated with 10 nmol/l rapamycin. A supra-therapeutic rapamycin
      concentration of 100 nmol/l significantly impaired glucose- and carbachol
      stimulated insulin secretion in rat islets and had a deleterious effect on the
      viability of rat and human islets, causing apoptosis of both alpha- and beta
      cells.

PMID- 14578292
TI  - Identification of subjects with insulin resistance and beta-cell dysfunction
      using alternative definitions of the metabolic syndrome.
AB  - Recently, the metabolic syndrome (MetS) has attracted much attention as a risk
      cluster for cardiovascular disease. Although it is believed that individuals with
      the MetS have insulin resistance (IR), there are few data using direct measures
      of IR such as glucose clamps or frequently sampled intravenous glucose tolerance
      tests (FSIGTTs). We examined associations of MetS with FSIGTT-derived measures of
      insulin sensitivity and secretion among nondiabetic subjects in the Insulin
      Resistance Atherosclerosis Study. Two sets of MetS criteria were evaluated: those
      from the 1999 World Health Organization (WHO) and the 2001 National Cholesterol
      Education Program (NCEP). Both WHO and NCEP MetS definitions were significantly
      associated with risk of being in the lowest quartile of directly measured insulin
      sensitivity (P < 0.0001 for all subjects as well as within ethnic subgroups).
      However, the associations with WHO-MetS were stronger for all subjects combined
      (WHO: odds ratio [OR] = 10.2; 95% CI 7.5-13.9; NCEP: OR = 4.6; 3.4-6.2) and in
      separate analyses of non-Hispanic whites, blacks, and Hispanics. WHO and NCEP
      MetS definitions were also significantly associated with risk of being in the
      lowest quartile of insulin sensitivity-adjusted acute insulin response (AIR) and
      disposition index (DI; all P < 0.01), although the associations were generally
      weaker than those for insulin sensitivity and there was no difference between the
      two definitions in all subjects combined (low AIR, WHO: OR = 1.7, 1.2-2.4; NCEP:
      OR = 1.7, 1.2-2.5). There were, however, a number of ethnic differences,
      including a stronger association of NCEP-MetS with low AIR among blacks. WHO-MetS
      was significantly more sensitive than NCEP-MetS in detecting low insulin
      sensitivity (65.4 vs. 45.6%, respectively; P < 0.0001), with no significant
      differences in specificity between the definitions (84.4 vs. 84.6%; P = 0.91),
      although WHO-MetS had a larger area under the receiver operating characteristic
      curve (75% vs. 65%; P < 0.0001). In conclusion, although both the WHO and NCEP
      MetS criteria identify nondiabetic individuals with low insulin sensitivity, the
      associations were notably stronger using the WHO definition. The definitions are
      generally less useful for identifying those with low AIR or DI, although NCEP
      MetS seems to differentiate black subjects with insulin secretion defects.

PMID- 14578293
TI  - Contribution of elevated free fatty acid levels to the lack of glucose
      effectiveness in type 2 diabetes.
AB  - Increased circulating free fatty acids (FFAs) inhibit both hepatic and peripheral
      insulin action. Because the loss of effectiveness of glucose to suppress
      endogenous glucose production and stimulate glucose uptake contributes
      importantly to fasting hyperglycemia in type 2 diabetes, we examined whether the
      approximate twofold elevations in FFA characteristic of poorly controlled type 2
      diabetes contribute to this defect. Glucose levels were raised from 5 to 10
      mmol/l while maintaining fixed hormonal conditions by infusing somatostatin with
      basal insulin, glucagon, and growth hormone. Each individual was studied at two
      FFA levels: with (NA+) and without (NA-) infusion of nicotinic acid in nine
      individuals with poorly controlled type 2 diabetes (HbA(1c) = 10.1 +/- 0.7%) and
      with (LIP+) and without (LIP-) infusion of lipid emulsion in nine nondiabetic
      individuals. Elevating FFA to approximately 500 micro mol/l blunted the ability
      of glucose to suppress endogenous glucose production (LIP- = -48% vs. LIP+ = 
      28%; P < 0.01) and increased glucose uptake (LIP- = 97% vs. LIP+ = 51%; P < 0.01)
      in nondiabetic individuals. Raising FFA also blunted the endogenous glucose
      production response in 10 individuals with type 2 diabetes in good control
      (HbA(1c) = 6.3 +/- 0.3%). Conversely, normalizing FFA nearly restored the
      endogenous glucose production (NA- = -7% vs. NA+ = -41%; P < 0.001) and glucose
      uptake (NA- = 26% vs. NA+ = 64%; P < 0.001) responses to hyperglycemia in
      individuals with poorly controlled type 2 diabetes. Thus, increased FFA levels
      contribute substantially to the loss of glucose effectiveness in poorly
      controlled type 2 diabetes.

PMID- 14578295
TI  - Extracellular glucose in rat ventromedial hypothalamus during acute and recurrent
      hypoglycemia.
AB  - The activity of neurons in the ventromedial hypothalamus (VMH) important for
      initiating compensatory responses to hypoglycemia is influenced by ambient
      glucose concentration. In the present study, we used in vivo microdialysis to
      evaluate interstitial glucose concentrations in rat VMH under various glycemic
      conditions. Using the zero-net-flux method, steady-state glucose concentration in
      the VMH was approximately 20% of blood glucose (approximately 1.4 mmol/l) in fed
      rats but approximately 14% of blood glucose (approximately 0.7 mmol/l) in
      overnight-fasted rats. During moderate hypoglycemia VMH glucose declined in
      parallel with blood glucose; however, VMH glucose decreased to a greater degree
      than blood glucose during a more severe hypoglycemic episode, falling to 10 +/-
      1.2% of blood levels (P < 0.01). To determine whether VMH glucose concentrations
      were influenced by recurrent episodes of hypoglycemia a second zero-net-flux
      study was conducted. Steady-state glucose concentrations in the VMH were
      approximately 20% lower after three episodes of recurrent hypoglycemia, a value
      17.8 +/- 0.8% of blood glucose, although the relative change in VMH glucose
      levels during the first and fourth hypoglycemic episodes were similar. From these
      results, we conclude that interstitial glucose concentrations in the VMH are not
      maintained at a constant level and are more dynamic than previously proposed.

PMID- 14578294
TI  - Prevalence and clinicopathological characteristics of islet amyloid in chinese
      patients with type 2 diabetes.
AB  - Islet amyloid has been suggested to be an important link between insulin
      resistance and beta-cell dysfunction in type 2 diabetes. To investigate the
      prevalence and clinicopathological characteristics of islet amyloid, we examined
      consecutive autopsies of 235 Chinese patients with type 2 diabetes and 533
      nondiabetic subjects. Islet amyloid deposits were identified using Congo red
      staining and quantitated by image analysis. We found that 3.0% of the nondiabetic
      subjects versus 39.6% of the diabetic patients displayed islet amyloid (P <
      0.001). In diabetic patients, the amyloid deposits occupied a mean islet area of
      36.2%, which was positively associated with BMI, blood pressure, and glycemic
      control. Pancreatic fibrosis and fat infiltration were more frequently found in
      diabetic patients with islet amyloid than those without islet amyloid, whereas
      pancreatic arteriosclerosis was identified in all diabetic patients. These
      findings suggest that islet amyloid deposits reflect greater insulin resistance
      and islet failure in a subgroup of type 2 diabetic patients. Islet failure may
      also have been exacerbated by fat infiltration, fibrosis, and arteriosclerosis.
      Optimal blood pressure and metabolic control may reduce these pathological
      changes and help preserve islet cell mass.

PMID- 14578296
TI  - Counterregulatory hormone and symptom responses to insulin-induced hypoglycemia
      in the postprandial state in humans.
AB  - Plasma counterregulatory hormones and symptoms were measured during hypoglycemia
      in the postprandial and in the fasting state in humans to establish differences
      in physiological responses. We studied 8 nondiabetic subjects and 10 subjects
      with type 1 diabetes on two different occasions during clamped insulin-induced
      hypoglycemia (2.4 mmol/l) in the sitting position. On one occasion, subjects ate
      a standard mixed meal, and on the other they remained fasting. In response to
      postprandial as compared with fasting hypoglycemia, nondiabetic subjects
      exhibited lower total symptom scores (6.6 +/- 0.4 vs. 11.5 +/- 0.8, P = 0.001),
      which was due to less hunger (1.1 +/- 0.1 vs. 4.2 +/- 0.2), lower suppression of
      plasma C-peptide (0.23 +/- 0.1 vs. 0.08 +/- 0.07 nmol/l, P = 0.032), and greater
      responses of plasma glucagon (248 +/- 29 vs. 163 +/- 25 ng x l(-1) x min(-1), P =
      0.018), plasma adrenaline (4.5 +/- 0.6 vs. 3.1 +/- 0.4 nmol x l(-1) x min(-1), P
      = 0.037), norepinephrine (3.8 +/- 0.3 vs. 3.2 +/- 0.2 nmol x l(-1) x min(-1), P =
      0.037), and pancreatic polypeptide (217 +/- 12 vs. 159 +/- 22 pmol x l(-1) x min(
      1), P = 0.08). Except for plasma C-peptide, responses in diabetic subjects were
      similarly affected. Notably, in diabetic subjects responses of glucagon, which
      were absent in the fasting state, nearly normalized after a meal. In conclusion,
      in the postprandial compared with the fasting hypoglycemic state, total symptoms
      are less, but counterregulatory hormones are greater and responses of glucagon
      nearly normalize in type 1 diabetic subjects.

PMID- 14578297
TI  - Chronic exposure to interleukin-6 causes hepatic insulin resistance in mice.
AB  - Interleukin (IL)-6 is one of several proinflammatory cytokines associated with
      the insulin resistance of obesity and type 2 diabetes. There is, however, little
      direct evidence in vivo for a causative role of IL-6 in insulin resistance. Here,
      a 5-day constant subcutaneous infusion of hIL-6 before portal vein insulin
      challenge resulted in impairment of early insulin receptor signaling in the liver
      of mice. Importantly, the sixfold elevation of IL-6 attained with constant
      infusion was similar to levels reached in obesity. Consistent with an hepatic
      response to IL-6, STAT3 phosphorylation was increased in livers of IL-6-treated
      mice at 5 days. Chronic infusion of IL-6 also reduced hepatic insulin receptor
      autophosphorylation by 60% and tyrosine phosphorylation of insulin receptor
      substrates-1 and -2 by 60 and 40%, respectively. IL-6 had no effect on the mass
      of these proteins. IL-6 also decreased refeeding-dependent glucokinase mRNA
      induction by approximately 40%. Insulin tolerance tests revealed reduced insulin
      sensitivity. In contrast to hepatic insulin receptor signal transduction, 5-day
      IL-6 exposure failed to suppress skeletal muscle insulin receptor signal
      transduction. These data suggest that chronic IL-6 treatment selectively impairs
      hepatic insulin signaling in vivo, further supporting a role for IL-6 in hepatic
      insulin resistance of obesity.

PMID- 14578298
TI  - Timing of changes in interstitial and venous blood glucose measured with a
      continuous subcutaneous glucose sensor.
AB  - The objective of this study was to use a subcutaneous continuous glucose sensor
      to determine time differences in the dynamics of blood glucose and interstitial
      glucose. A total of 14 patients with type 1 diabetes each had two sensors
      (Medtronic/MiniMed CGMS) placed subcutaneously in the abdomen, acquiring data
      every 5 min. Blood glucose was sampled every 5 min for 8 h, and two liquid meals
      were given. A smoothing algorithm was applied to the blood glucose and
      interstitial glucose curves. The first derivatives of the glucose traces defined
      and quantified the timing of rises, peaks, falls, and nadirs. Altogether, 24
      datasets were used for the analysis of time differences between interstitial and
      blood glucose and between sensors in each patient. Time differences between blood
      and interstitial glucose ranged from 4 to 10 min, with the interstitial glucose
      lagging behind blood glucose in 81% of cases (95% CIs 72.5 and 89.5%). The mean
      (+/-SD) difference between the two sensors in each patient was 6.7 +/- 5.1 min,
      representing random variation in sensor response. In conclusion, there is a time
      lag of interstitial glucose behind blood glucose, regardless of whether glycemia
      is rising or falling, but intersensor variability is considerable in this sensor
      system. Comparisons of interstitial and blood glucose kinetics must take
      statistical account of variability between sensors.

PMID- 14578299
TI  - Intermittent high glucose enhances apoptosis related to oxidative stress in human
      umbilical vein endothelial cells: the role of protein kinase C and NAD(P)H
      oxidase activation.
AB  - The effects of intermittent and constant high glucose in the formation of
      nitrotyrosine and 8-hydroxydeoxyguanosine (markers of oxidative stress), as well
      as the possible linkage between oxidative stress and apoptosis in endothelial
      cells, have been evaluated. Stable high glucose increased nitrotyrosine, 8
      hydroxydeoxyguanosine (8-OHdG), and apoptosis levels. However, these effects were
      more pronounced in intermittent high glucose. Protein kinase C (PKC) was elevated
      in both such conditions, particularly in intermittent glucose. The adding of the
      PKC inhibitors bisindolylmaleimide-I and LY379196, a specific inhibitor of PKC
      beta isoforms, normalized nitrotyrosine and reduced 8-OHdG concentration and cell
      apoptosis in both stable and intermittent high glucose. Similar results were
      obtained with the MnSOD mimetic Mn(III)tetrakis(4-benzoic acid)porphyrin chloride
      that normalized nitrotyrosine, 8-OHdG, and apoptosis and inhibited PKC
      activation. NAD(P)H oxidase was also measured. NAD(P)H oxidase components
      p47phox, p67phox, and p22phox was overexpressed during both stable and
      intermittent high glucose. PKC inhibition and MnSOD mimetic normalized this
      phenomenon. In conclusion, our study shows that the exposure of endothelial cells
      to both stable and intermittent high glucose stimulates reactive oxygen species
      overproduction also through PKC-dependent activation of NAD(P)H oxidase, leading
      to increased cellular apoptosis. Our data suggest that glucose fluctuations may
      also be involved in the development of vascular injury in diabetes.

PMID- 14578300
TI  - Adverse effects of dietary glycotoxins on wound healing in genetically diabetic
      mice.
AB  - Advanced glycoxidation end products (AGEs) are implicated in delayed diabetic
      wound healing. To test the role of diet-derived AGE on the rate of wound healing,
      we placed female db/db (+/+) (n = 55, 12 weeks old) and age-matched control db/db
      (+/-) mice (n = 45) on two diets that differed only in AGE content (high [H-AGE]
      versus low [L-AGE] ratio, 5:1) for 3 months. Full-thickness skin wounds (1 cm)
      were examined histologically and for wound closure. Serum 24-h urine and skin
      samples were monitored for N(epsilon)-carboxymethyl-lysine and methylglyoxal
      derivatives by enzyme-linked immunosorbent assays. L-AGE-fed mice displayed more
      rapid wound closure at days 7 and 14 (P < 0.005) and were closed completely by
      day 21 compared with H-AGE nonhealed wounds. Serum AGE levels increased by 53% in
      H-AGE mice and decreased by 7.8% in L-AGE mice (P < 0.04) from baseline. L-AGE
      mice wounds exhibited lower skin AGE deposits, increased epithelialization,
      angiogenesis, inflammation, granulation tissue deposition, and enhanced collagen
      organization up to day 21, compared with H-AGE mice. Reepithelialization was the
      dominant mode of wound closure in H-AGE mice compared with wound contraction that
      prevailed in L-AGE mice. Thus, increased diet-derived AGE intake may be a
      significant retardant of wound closure in diabetic mice; dietary AGE restriction
      may improve impaired diabetic wound healing.

PMID- 14578301
TI  - Influence of type 2 diabetes on functional and structural properties of coronary
      artery bypass conduits.
AB  - Recent studies have reported a high incidence of postoperative unfavorable
      cardiac-related events in patients with diabetes who underwent coronary artery
      bypass grafting (CABG). Structural and functional characteristics of CABG
      conduits, which have been shown to play an important role in patient outcome
      after myocardial revascularization, have not been fully investigated in diabetic
      subjects. Therefore, we sought to determine the influence of adult-onset diabetes
      on vasoreactivity and morphological profile of venous and arterial grafts. Of the
      160 consecutive patients enrolled in the study, 90 were diagnosed with type 2
      diabetes and 70 did not have diabetes (control group). All patients underwent
      evaluation of glucose control before surgery. Tissue specimens were collected
      from left internal thoracic artery (LITA) and saphenous vein (SV) grafts
      harvested during elective CABG. Functional tests were performed to assess
      contractile and vasodilative responses of bypass conduits. Histological
      evaluation was carried out to examine vessel wall structure. Univariate and
      multivariate analyses were performed to correlate the preoperative factors
      related to the control of the endocrine disorder with histological findings.
      Patient medical history and demographics did not differ between the groups.
      Diabetic patients showed significant microalbuminuria and higher plasma levels of
      C-peptide and GHb as compared with nondiabetic subjects. Functional tests of the
      LITA segments revealed no difference between groups with regard to contractile
      and vasodilative responses. In contrast, significant impairment in the
      endothelium-related vasodilation of the SV grafts was observed in diabetic
      subjects. Histological studies showed structural preservation of the arterial
      conduits in both groups. However, marked intimal abnormalities (also
      atherosclerotic calcified plaques) were detected in SV grafts harvested from
      diabetic patients. Logistic regression analysis showed that high levels of
      proteinuria and GHb were independent predictors of advanced structural
      degeneration of SV conduits. Treatment modality, duration of diabetes, and other
      demographic or metabolic factors were found to have no influence on the
      morphological characteristics of SV conduits. In conclusion, biological
      properties of LITA conduits for CABG were preserved in diabetic patients.
      However, these patients frequently showed impairment of the endothelium-dependent
      vasorelaxation and intimal degeneration of SV grafts. The extent of structural
      abnormalities of SV grafts was inversely correlated with the efficacy of the
      metabolic control of the endocrine disorder. Further studies are required to
      conclusively correlate preoperative SV graft abnormalities with postoperative
      conduit patency rate and the occurrence of adverse cardiac-related events in
      diabetic subjects.

PMID- 14578302
TI  - Leptin and wound inflammation in diabetic ob/ob mice: differential regulation of
      neutrophil and macrophage influx and a potential role for the scab as a sink for
      inflammatory cells and mediators.
AB  - In this study, we investigated the role of leptin for the inflammatory response
      in diabetes-impaired skin repair. We demonstrated, that systemic treatment of
      diabetic ob/ob mice with leptin blunted polymorphonuclear neutrophil (PMN), but
      not macrophage influx into the wound site. Closed wounds of leptin-administered
      mice were characterized by tremendous numbers of macrophage within the
      granulation tissue. In line, leptin supplementation potently attenuated
      epithelium-derived CXC- but not CC-chemokine expression. PMNs were preferentially
      located in the scab, but macrophages predominantly resided within the wound
      stroma of the animals. The scabs of nonhealing wounds were most likely to serve
      as sinks for bioactive inflammatory mediators, which were still capable to drive
      gene expression in keratinocytes in vitro. Differential effects of leptin on PMN
      and macrophage axes of inflammation must be indirect, as topical administration
      of leptin onto wounds of ob/ob mice did not reduce PMN influx into the wounded
      areas. Moreover, caloric-restricted, pair-fed ob/ob mice were characterized by
      impaired healing conditions that were associated with persisting PMNs.
      Interestingly, we documented the absence of leptin receptor expression in human
      diabetic foot ulcers. Thus, we show that leptin might function as a regulatory
      link between the endocrine and the immune system in the context of skin repair.

PMID- 14578303
TI  - Effect of type 1 diabetes on the gender difference in coronary artery
      calcification: a role for insulin resistance? The Coronary Artery Calcification
      in Type 1 Diabetes (CACTI) Study.
AB  - The objective of this is study was to examine whether estimated insulin
      resistance and insulin resistance-related factors are associated with coronary
      artery calcification (CAC) in 1,420 asymptomatic participants in the Coronary
      Artery Calcification in Type 1 Diabetes (CACTI) study. A total of 656 patients
      with type 1 diabetes and 764 control subjects aged 20-55 years were examined. CAC
      was assessed by electron-beam computed tomography. Insulin resistance was
      computed with linear regression based on an equation previously validated in
      clamp studies on type 1 diabetic adults. Insulin resistance was associated with
      CAC (OR 1.6 in type 1 diabetes and 1.4 in control subjects, P < 0.001),
      independent of coronary artery disease risk factors. There was a male excess of
      CAC in control subjects (OR 2.7, adjusted for age, smoking, and LDL and HDL
      cholesterol levels) and in type 1 diabetic patients (OR 2.2, adjusted for the
      same factors and diabetes duration). After adjusting for insulin resistance, the
      CAC male excess in diabetic patients decreased from OR 2.2 (P < 0.001) to 1.8 (P
      = 0.04). After adjustment for waist-to-hip ratio, waist circumference, or
      visceral fat, the gender difference in CAC was not significant in diabetic
      subjects. In conclusion, gender differences in insulin resistance-associated fat
      distribution may explain why type 1 diabetes increases coronary calcification in
      women relatively more than in men.

PMID- 14578304
TI  - Linkage analysis of a composite factor for the multiple metabolic syndrome: the
      National Heart, Lung, and Blood Institute Family Heart Study.
AB  - Recent studies have demonstrated significant genetic and phenotypic correlation
      underlying the clustering of traits involved in the multiple metabolic syndrome
      (MMS). The aim of this study was to identify chromosomal regions contributing to
      MMS-related traits represented by composite factors derived from factor analysis.
      Data from the National Heart, Lung, and Blood Institute (NHLBI) Family Heart
      Study were subjected to a maximum likelihood-based factor analysis. These
      analyses generated an MMS factor that was loaded by BMI, waist-to-hip ratio,
      subscapular skinfold, triglycerides, HDL, homeostasis model assessment index,
      plasminogen activator inhibitor-1 antigen, and serum uric acid. Genetic data were
      obtained for 2,467 subjects from 387 three-generation families (402 markers, the
      NHLBI Mammalian Genotyping Service) and 1,082 subjects from 256 sibships (243
      markers, the Utah Molecular Genetics Laboratory). Multipoint variance components
      linkage analysis (GENEHUNTER version 2.1) of the MMS factor was conducted in the
      combined marker set sample. The greatest evidence for linkage was found on
      chromosome 2, with a peak LOD of 3.34 at 240 cM. Suggestive linkage was also
      observed for regions on chromosomes 7, 12, 14, and 15. In summary, a genomic
      region on chromosome 2 may contain a pleiotropic locus contributing to the
      clustering of MMS-related phenotypes.

PMID- 14578305
TI  - Association of solute carrier family 12 (sodium/chloride) member 3 with diabetic
      nephropathy, identified by genome-wide analyses of single nucleotide
      polymorphisms.
AB  - To identify genetic elements that might confer susceptibility to diabetic
      nephropathy, we performed a genome-wide analysis of gene-based single nucleotide
      polymorphisms (SNPs) in a large cohort of Japanese patients with diabetes. In
      case-control association studies, patients with type 2 diabetes were divided into
      two groups, one having retinopathy as well as overt nephropathy and the other
      (the control group) having diabetic retinopathy but with no signs of renal
      involvement. Genotyping of these patients at >55,000 SNP loci indicated a gene
      encoding solute carrier family 12 member 3 (SLC12A3) to be a good candidate for
      the susceptibility to diabetic nephropathy, in view of a significant association
      of one landmark SNP located in the 24th intron (chi(2) = 15.4, P = 0.000087, odds
      ratio = 2.53 [95% CI 1.57-4.09]). Subsequent analysis of additional genetic
      variations in this gene identified several SNPs that were significantly
      associated with nephropathy, especially one in exon 23 (+78 G to A: Arg913Gln,
      chi(2) = 18.5, P = 0.00002, odds ratio = 2.53 [95% CI 1.64-3.90]). The results
      implicated that substitution of Arg913 to Gln in the SLC12A3 gene might reduce
      the risk to develop diabetic nephropathy and suggested that the gene product
      might be a potential target for the prevention or treatment of this disease.

PMID- 14578306
TI  - Permanent neonatal diabetes caused by glucokinase deficiency: inborn error of the
      glucose-insulin signaling pathway.
AB  - Neonatal diabetes can be either permanent or transient. We have recently shown
      that permanent neonatal diabetes can result from complete deficiency of
      glucokinase activity. Here we report three new cases of glucokinase-related
      permanent neonatal diabetes. The probands had intrauterine growth retardation
      (birth weight <1,900 g) and insulin-treated diabetes from birth (diagnosis within
      the first week of life). One of the subjects was homozygous for the missense
      mutation Ala378Val (A378V), which is an inactivating mutation with an activity
      index of only 0.2% of wild-type glucokinase activity. The second subject was
      homozygous for a mutation in the splice donor site of exon 8 (intervening
      sequence 8 [IVS8] + 2T-->G), which is predicted to lead to the synthesis of an
      inactive protein. The third subject (second cousin of subject 2) was a compound
      heterozygote with one allele having the splice-site mutation IVS8 + 2T-->G and
      the other the missense mutation Gly264Ser (G264S), a mutation with an activity
      index of 86% of normal activity. The five subjects with permanent neonatal
      diabetes due to glucokinase deficiency identified to date are characterized by
      intrauterine growth retardation, permanent insulin-requiring diabetes from the
      first day of life, and hyperglycemia in both parents. Autosomal recessive
      inheritance and enzyme deficiency are features typical for an inborn error of
      metabolism, which occurred in the glucose-insulin signaling pathway in these
      subjects.

PMID- 14578307
TI  - The endotoxin receptor TLR4 polymorphism is not associated with diabetes or
      components of the metabolic syndrome.

PMID- 14578308
TI  - Standardized testing for mutations in familial Mediterranean fever.

PMID- 14578309
TI  - Summarizing studies of diagnostic test performance.

PMID- 14578310
TI  - Report of the National Heart, Lung, and Blood Institute Workshop on
      Lipoprotein(a) and Cardiovascular Disease: recent advances and future directions.
AB  - It has been estimated that approximately 37% of the US population judged to be at
      high risk for developing coronary artery disease (CAD), based on the National
      Cholesterol Education Program guidelines, have increased plasma lipoprotein(a)
      [Lp(a)], whereas Lp(a) is increased in only 14% of those judged to be at low
      risk. Therefore, the importance of establishing a better understanding of the
      relative contribution of Lp(a) to the risk burden for CAD and other forms of
      vascular disease, as well as the underlying mechanisms, is clearly evident.
      However, the structural complexity and size heterogeneity of Lp(a) have hindered
      the development of immunoassays to accurately measure Lp(a) concentrations in
      plasma. The large intermethod variation in Lp(a) values has made it difficult to
      compare data from different clinical studies and to achieve a uniform
      interpretation of clinical data. A workshop was recently convened by the National
      Heart, Lung, and Blood Institute (NHLBI) to evaluate our current understanding of
      Lp(a) as a risk factor for atherosclerotic disorders; to determine how future
      studies could be designed to more clearly define the extent to which, and
      mechanisms by which, Lp(a) participates in these processes; and to present the
      results of the NHLBI-supported program for the evaluation and standardization of
      Lp(a) immunoassays. This report includes the most recent data presented by the
      workshop participants and the resulting practical and research recommendations.

PMID- 14578311
TI  - Use of tandem mass spectrometry for multianalyte screening of dried blood
      specimens from newborns.
AB  - BACKGROUND: Over the past decade laboratories that test for metabolic disorders
      have introduced tandem mass spectrometry (MS/MS), which is more sensitive,
      specific, reliable, and comprehensive than traditional assays, into their newborn
      screening programs. MS/MS is rapidly replacing these one-analysis, one
      metabolite, one-disease classic screening techniques with a one-analysis, many
      metabolites, many-diseases approach that also facilitates the ability to add new
      disorders to existing newborn-screening panels. METHODS: During the past few
      years experts have authored many valuable articles describing various approaches
      to newborn metabolic screening by MS/MS. We attempted to document key
      developments in the introduction and validation of MS/MS screening for metabolic
      disorders. Our approach used the perspective of the metabolite and which diseases
      may be present from its detection rather than a more traditional approach of
      describing a disease and noting which metabolites are increased when it is
      present. CONTENT: This review cites important historical developments in the
      introduction and validation of MS/MS screening for metabolic disorders. It also
      offers a basic technical understanding of MS/MS as it is applied to multianalyte
      metabolic screening and explains why MS/MS is well suited for analysis of amino
      acids and acylcarnitines in dried filter-paper blood specimens. It also describes
      amino acids and acylcarnitines as they are detected and measured by MS/MS and
      their significance to the identification of specific amino acid, fatty acid, and
      organic acid disorders. CONCLUSIONS: Multianalyte technologies such as MS/MS are
      suitable for newborn screening and other mass screening programs because they
      improve the detection of many diseases in the current screening panel while
      enabling expansion to disorders that are now recognized as important and need to
      be identified in pediatric medicine.

PMID- 14578312
TI  - Critique of the Guide to the expression of uncertainty in measurement method of
      estimating and reporting uncertainty in diagnostic assays.
AB  - BACKGROUND: The Guide to the Expression of Uncertainty in Measurement (GUM)
      provides instructions for constructing uncertainty intervals for a measurement.
      This method is usually reserved for reference materials, but GUM has been
      recently proposed as a way to express uncertainty for commercial diagnostic
      assays. METHODS: Using the official GUM standard and published applications of
      GUM to commercial diagnostic assays, I undertook an analysis to evaluate whether
      applying GUM to commercial diagnostic assays is warranted. RESULTS: Certain
      important assays, such as troponin I, would not be candidates for GUM because
      troponin I is not a well-defined physical quantity. Unlike definitive methods, in
      which efforts are taken to detect and eliminate all systematic error sources,
      commercial assays often trade off features such as ease of use and cost with
      accuracy and allow systematic errors to be present as long as the overall
      accuracy meets the medical need goal. Laboratories are hindered in preparing GUM
      models because the knowledge required to specify some systematic errors is often
      available only to manufacturers. Some non-GUM methods to estimate uncertainty
      rely on observed data, which include both known and unknown sources of error. The
      occurrence of large, unknown errors for assays in routine use (e.g., outliers) is
      not unusual because diagnostic assays must be chemically specific in the presence
      of thousands of potentially interfering substances. There is no provision in GUM
      to deal with unexplained outliers, which may lead to uncertainty intervals that
      are not wide enough. Some clinicians assume that diagnostic assay results have
      little uncertainty. This situation may be made worse by including an uncertainty
      interval, which implies certification. CONCLUSIONS: Evaluations for accuracy
      (total analytical error) based on describing the distribution of result
      differences between commercial assays and reference methods indicate that some
      assays have a few results with large differences (e.g., outliers). This leads to
      a wide accuracy interval (total analytical error limits). It is unlikely that GUM
      would be able to predict these wide intervals, especially because there is little
      or no provision for outlier treatment in GUM. Presenting too narrow GUM
      uncertainty intervals to clinicians would be misleading. The modeling used by
      practitioners of the GUM method is potentially useful in improving quality, but
      commercial diagnostic assays are not ready for GUM uncertainty statements.

PMID- 14578313
TI  - The Guide to expression of uncertainty in measurement approach for estimating
      uncertainty: an appraisal.
AB  - BACKGROUND: The aim of the Guide to Expression of Uncertainty in Measurement
      (GUM) is to harmonize the different practices for estimating and reporting
      uncertainty of measurement. Although there are clear advantages in having a
      common approach for evaluating uncertainty, application of the GUM approach to
      chemistry measurements is not straightforward. In the above commentary, Krouwer
      suggests that the GUM approach should not be applied to diagnostic assays,
      because (a) the quality of diagnostic assays is to low, and (b) the GUM
      uncertainty intervals are too narrow to predict the outliers that occasionally
      trouble these methods. METHODS: Some of the examples presented by Krouwer are
      reviewed. Sodium measurements are modeled mathematically to illustrate the GUM
      approach to uncertainty. A standardized uncertainty evaluation process is
      presented. RESULTS: Modeling of sodium measurements demonstrates how the GUM
      uncertainty interval reflects the treatment of a bias: The width of the
      uncertainty interval varied depending on whether a correction for a calibrator
      lot bias was applied, but in both cases it was consistent with the distribution
      of measurement results. Expanding the uncertainty interval to include outliers
      runs counter to the definition of uncertainty. Used appropriately, the GUM
      uncertainty can be helpful in detecting outliers. In standardizing the
      uncertainty evaluation, the importance of the analytical imprecision and
      traceability was emphasized. It is problematic that manufacturers of commercial
      assays rarely inform about the uncertainty of the values assigned to the
      calibrators. As demonstrated by an example, external quality-assurance data may
      be used to estimate this uncertainty. CONCLUSIONS: The GUM uncertainty should be
      applied to measurements in laboratory medicine because it may actually support
      the forces that drive the work on improving the quality of measurement
      procedures. However, it is important that the GUM approach is made more
      manageable by standardizing the uncertainty evaluation procedure as much as
      possible. It is essential to focus on the traceability and uncertainty of
      calibrators and reagents supplied by manufacturers of assays. Information about
      uncertainty is necessary in the evaluation of the uncertainty associated with
      manufacturers' measurement procedures, and in general it may force manufacturers
      to increase their efforts in improving the metrologic and analytical quality of
      their products.

PMID- 14578314
TI  - Capillary electrophoresis in diagnosis and monitoring of adenosine deaminase
      deficiency.
AB  - BACKGROUND: The diagnosis and monitoring of severe combined immunodeficiency
      disease (SCID) attributable to adenosine deaminase (ADA) deficiency requires
      measurements of ADA, purine nucleoside phosphorylase (PNP), and S-adenosyl-L
      homocysteine-hydrolase (SAHH) activity and of deoxyadenosine metabolites. We
      developed capillary electrophoresis (CE) methods for the detection of key
      diagnostic metabolites and evaluation of enzyme activities. METHODS:
      Deoxyadenosine metabolites were separated in 30 mmol/L sodium borate-10 mmol/L
      sodium dodecyl sulfate (pH 9.80) at 25 degrees C on a 60-cm uncoated capillary.
      For determination of enzyme activities, substrate-product separation and
      measurements were carried out in 20 mmol/L sodium borate (pH 10.00) at 25 degrees
      C on a 42-cm uncoated capillary. RESULTS: Deoxynucleotides and deoxyadenosine
      were readily detectable in erythrocytes and urine, respectively. Both methods
      were linear in the range 2-500 micro mol/L (r >0.99). Intra- and interassay CV
      were <4%. Enzyme activities were linear with respect to sample amounts in the
      incubation mixture and to incubation time (r >0.99 for both). In erythrocytes
      from healthy individuals, mean (SD) ADA activity was 5619 (2584) nmol/s per liter
      of packed cells. In erythrocytes of SCID patients at diagnosis, ADA activity was
      56.9 (48.3) nmol/s per liter of packed cells; SAHH activity was also much
      reduced. PNP activity was similar in patients and controls. CONCLUSIONS: CE can
      be used to test ADA deficiency and enables rapid assessment of ADA expression in
      hematopoietic cells of SCID patients during therapy.

PMID- 14578315
TI  - Apolipoprotein C-III isofocusing in the diagnosis of genetic defects in O-glycan
      biosynthesis.
AB  - BACKGROUND: Defects in the biosynthesis of N-glycans may be found by isoelectric
      focusing (IEF) of plasma transferrin. No test is available to demonstrate O
      glycan biosynthesis defects. METHODS: We used isoforms of apolipoprotein C-III
      (apoC-III) as a marker for the biosynthesis of core 1 mucin type O-glycans.
      Plasma samples from patients with primary defects and secondary alterations in N
      glycan biosynthesis were studied by apoC-III isofocusing. RESULTS: Age-related
      reference values for apoC-III were determined. Plasma samples from patients with
      the primary congenital disorders of glycosylation (CDG) types Ia-Ic, Ie, If, IIa,
      and IId all showed a normal apoC-III isofocusing profile. Plasma from two
      patients with CDG type IIx were tested: one showed a normal apoC-III
      distribution, whereas the other showed a hypoglycosylation profile. In plasma
      from patients with hemolytic uremic syndrome (HUS), a hypoglycosylation profile
      was obtained. CONCLUSIONS: IEF of apoC-III is a rapid and simple technique that
      may be used as a screening assay for abnormalities in core 1 mucin type O
      glycans. Evidence that a patient in this study has a primary genetic defect
      affecting both N- and O-glycosylation provides the first example of an inborn
      error of metabolism affecting the biosynthesis of core 1 mucin type O-glycans.
      Our data narrow the options for the position of the primary defect in this
      patient down to a step in the biosynthesis, activation, or transfer of galactose
      or N-acetylneuraminic acid to both N- and O-glycans. Circulating neuraminidase
      excreted by Streptococcus pneumoniae caused the high percentage of asialo apoC
      III in two HUS patients.

PMID- 14578316
TI  - Turbidimetric D-dimer test in the diagnosis of pulmonary embolism: a
      metaanalysis.
AB  - BACKGROUND: Clinicians in outpatient clinics and emergency departments desire an
      accurate quantitative D-dimer assay. The study objective was to evaluate the
      diagnostic performance characteristics of the latex turbidimetric D-dimer test in
      the diagnosis of pulmonary embolism (PE) in the emergency department population.
      METHODS: We conducted a search of MEDLINE, EMBASE, and bibliographies of previous
      systematic reviews with no language restriction. Experts in the field of PE
      research were contacted to identify unpublished studies. Prospective
      investigations involving predominately outpatient populations with suspected PE
      that used a turbidimetric D-dimer test were included. Two authors extracted data
      independently and assessed study quality based on the composition of the patient
      spectrum and the reference standard used. Consensus was reached by conference.
      The analysis was based on a summary ROC curve and combining sensitivity and
      specificity independently across studies using a random-effects model. RESULTS:
      The search yielded 264 publications and 2 unpublished studies. Nine studies met
      the inclusion criteria and provided a sample of 1901 individuals. Eight of the
      nine studies were homogeneous in terms of both sensitivity and specificity. One
      study had similar sensitivity but higher specificity. Combining the studies
      yielded an overall sensitivity of 0.93 (95% confidence interval, 0.89-0.96) and
      an overall specificity of 0.51 (95% confidence interval, 0.42-0.59). CONCLUSIONS:
      The turbidimetric D-dimer test is sensitive but nonspecific for the detection of
      PE in the emergency department setting. D-Dimer tests using latex turbidimetric
      methods appear to have test characteristics comparable to those for ELISA
      methods.

PMID- 14578317
TI  - Analyte comigrating with trisialotransferrin during capillary zone
      electrophoresis of sera from patients with cancer.
AB  - BACKGROUND: Serum concentrations of monoglycosylated isoforms of transferrin are
      increased by chronic ethanol intake. We investigated transferrin glycosylation in
      patients with cancer, in which aberrant glycosylation is also induced. METHODS:
      We used a P/ACE 5000 series capillary zone electrophoresis (CZE) apparatus and a
      CZE carbohydrate-deficient transferrin reagent set to study 200 cancer patients
      who consumed alcohol moderately and 33 who were alcohol abusers; we then compared
      these patients with 56 healthy teetotalers, 89 moderate, and 112 excessive
      alcohol drinkers without known malignancies. Transferrin isoforms were identified
      by immunosubtraction with anti-human transferrin polyclonal antibody. RESULTS:
      Seven peaks, P0-P6, were visualized and completely or partly immunosubtracted
      when CZE separation was performed at pH 8.5. P0 was present in 95% of alcohol
      abusers with or without cancer. P3 was significantly higher in cancer patients
      and was only partly immunosubtracted as trisialotransferrin in all groups. The
      comigrating analyte was not altered by papain, precipitation by ethanol, or
      extraction by organic solvents, but was sensitive to acid hydrolysis, suggesting
      a polysaccharide structure. When isolated at pH 8.25, this analyte was higher in
      cancer patients. ROC curve analysis identified localized malignant neoplasia at
      P3 values above 5.8% of total transferrin (sensitivity, 0.78; specificity, 0.87),
      regardless of alcohol consumption. Disseminated cancers were better
      differentiated above 8% (sensitivity, 0.94; specificity, 0.96). CONCLUSIONS:
      Malignant neoplasia, unlike excessive ethanol intake, did not alter the addition
      of two N-glycans to transferrin. A peak comigrating with trisialotransferrin had
      characteristics of a polysaccharide in all adults and was increased in sera of
      patients with cancer.

PMID- 14578318
TI  - Rapid separation of LDL subclasses by iodixanol gradient ultracentrifugation.
AB  - BACKGROUND: A predominance of small, dense LDL (sdLDL) confers in excess of a
      threefold increase in coronary heart disease (CHD) risk. The conventional method
      for the detection of sdLDL, salt density gradient ultracentrifugation (DGUC) has
      been superseded by more rapid techniques. This report presents novel methodology
      for the separation of sdLDL by a combination of iodixanol density gradient
      centrifugation and digital photography. METHODS: LDL subclasses were separated in
      3 h from prestained plasma on a self-forming density gradient of iodixanol. LDL
      subclass profiles were generated by digital photography and gel-scan software.
      Plasma samples from 106 normo- and dyslipidemic individuals were used to optimize
      the gradient for the resolution of LDL heterogeneity. A subgroup of 47 LDL
      profiles were then compared with LDL subclasses separated by salt DGUC. RESULTS:
      The peak density of the predominant LDL band correlated significantly with the
      relative abundance (as a percentage) of sdLDL as resolved by salt DGUC (P
      <0.001). As shown previously, LDL isolated at a lighter density in iodixanol
      compared with salt gradients. A predominance of sdLDL corresponded to a peak
      density on iodixanol of 1.028 kg/L. This density and the area under the LDL
      profile lying above this density were sensitive and specific markers for the
      prediction of a predominance of sdLDL (P <0.001) and showed predictable
      associations with plasma triglycerides (r = 0.59; P <0.001) and HDL (r = -0.4; P
      <0.001). CONCLUSIONS: This simple method for the detection of sdLDL can
      differentiate a predominance of sdLDL, is highly reproducible, and can be used
      preparatively to isolate sdLDL.

PMID- 14578319
TI  - Fractional esterification rate of cholesterol and ratio of triglycerides to HDL
      cholesterol are powerful predictors of positive findings on coronary angiography.
AB  - BACKGROUND: We examined the predictive value of various clinical and biochemical
      markers for angiographically defined coronary artery disease (aCAD).
      Specifically, we assessed the value of the ratio of plasma triglyceride (TGs) to
      HDL-cholesterol (HDL-C) and the fractional esterification rate of cholesterol in
      plasma depleted of apolipoprotein B (apoB)-containing lipoproteins (FER(HDL)), a
      functional marker of HDL and LDL particle size. METHODS: Patients (788 men and
      320 women) undergoing coronary angiography were classified into groups with
      positive [aCAD(+)] and negative [aCAD(-)] findings. Patient age, body mass index,
      waist circumference, blood pressure (BP), medications, drinking, smoking,
      exercise habits, and plasma total cholesterol (TC), LDL-cholesterol (LDL-C), HDL
      unesterified cholesterol, HDL-C, TGs, FER(HDL), apoB, log(TG/HDL-C), and TC/HDL-C
      were assessed. Lipids and apoproteins were measured by standard laboratory
      procedures; FER(HDL) was determined by a radioassay. RESULTS: Members of the
      aCAD(+) group were older and had a higher incidence of smoking and diabetes than
      those in the aCAD(-) group. The aCAD(+) group also had higher TG, apoB, FER(HDL),
      and log(TG/HDL-C) and lower HDL-C values. aCAD(+) women had greater waist
      circumference and higher plasma TC and TC/HDL-C. aCAD(+) men, but not women, had
      higher plasma LDL-C. In the multivariate logistic model, the significant
      predictors of the presence of aCAD(+) were FER(HDL), age, smoking, and diabetes.
      If only laboratory tests were included in the multivariate logistic model,
      FER(HDL) appeared as the sole predictor of aCAD(+). Log(TG/HDL-C) was an
      independent predictor when FER(HDL) was omitted from multivariate analysis.
      CONCLUSIONS: FER(HDL) was the best laboratory predictor of the presence of
      coronary atherosclerotic lesions.

PMID- 14578320
TI  - Improved HPLC method for carbohydrate-deficient transferrin in serum.
AB  - BACKGROUND: There is need for a reference method for transferrin glycoforms in
      serum to which routine immunologic methods for the alcohol marker carbohydrate
      deficient transferrin (CDT) can be traceable. We describe an improved HPLC method
      for transferrin glycoforms. METHODS: Transferrin was iron-saturated by mixing the
      serum with ferric nitrilotriacetic acid, and lipoproteins were precipitated with
      dextran sulfate and calcium chloride. Separation of glycoforms was performed on a
      SOURCE 15Q anion-exchange column using salt gradient elution. Quantification
      relied on selective absorbance of the iron-transferrin complex at 470 nm. The
      relative amount of each glycoform was calculated as a percentage of the area
      under the curve, using baseline integration. RESULTS: The HPLC system provided
      reproducible separation and quantification of the asialo-, monosialo-, disialo-,
      trisialo-, tetrasialo-, pentasialo-, and hexasialotransferrin glycoforms. Most
      importantly, disialo- and trisialotransferrin were almost baseline separated. The
      intra- and interassay CV for disialotransferrin were <5%. Serum and the
      pretreated samples were stable for at least 2 days at 22 or 4 degrees C. Sera
      from 132 healthy controls contained [mean (SD)] 1.16 (0.25)% disialotransferrin,
      4.77 (1.36)% trisialotransferrin, 80.18 (2.01)% tetrasialotransferrin, and 13.88
      (1.69)% pentasialo- + hexasialotransferrin. In some cases of a high (>6%)
      trisialotransferrin, monosialotransferrin was detected at <0.25%.
      Asialotransferrin was not detected in control sera, but was detected in 57% of
      chronic heavy drinkers and in 62% of sera with >/=2% disialotransferrin.
      CONCLUSIONS: The HPLC method fulfills the requirements of a preliminary reference
      method for CDT and should work for any combination of serum transferrin
      glycoforms. This method could also be useful for confirming positive CDT results
      by immunoassays in medico-legal cases.

PMID- 14578322
TI  - Sensitive HPLC-fluorescence method for irinotecan and four major metabolites in
      human plasma and saliva: application to pharmacokinetic studies.
AB  - BACKGROUND: We developed gradient HPLC methods for quantification of the
      antimitotic drug irinotecan (CPT-11) and its four metabolites, SN-38, SN-38 G, 7
      ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino]-carbonyloxycamptothecin
      (APC), and 7-ethyl-10-[4amino-1-piperidino]-carbonyloxycamptothecin (NPC), as the
      sum of the lactone and carboxylate forms, in human plasma and saliva.
      Camptothecin was used as internal standard. METHODS: The sample pretreatment
      involved protein precipitation with methanol-acetonitrile (50:50 by volume)
      followed by acidification with hydrochloric acid to convert the lactone ring
      opened form into its lactone form, quantitatively. HPLC separation was performed
      on a Xterra RP18 column. The excitation wavelength was 370 nm, and the emission
      wavelength was set at 470 nm for the first 24 min and then at 534 nm for the next
      4 min. The stabilities of irinotecan and its four metabolites in plasma, saliva,
      and acidic extracts were also investigated under various conditions. RESULTS:
      Assays were linear in the tested range of 0.5-1000 micro g/L. For the five
      analytes, limits of quantification were 0.5 micro g/L in both matrices. The
      interassay imprecision (as relative standard deviation) was 3.2-14% in plasma and
      2.6-5.6% in saliva. Assay recoveries ranged from 92.8% to 111.2% for plasma and
      100.1% to 104.1% for saliva. Mean extraction recovery from plasma or saliva was
      90%. CONCLUSION: The developed assay can be used to determine pharmacokinetic
      parameters for CPT-11, SN-38, SN-38 G, APC, and NPC in plasma and saliva from
      patients with metastatic colorectal cancer.

PMID- 14578321
TI  - Pharmacodynamic approach to immunosuppressive therapies using calcineurin
      inhibitors and mycophenolate mofetil.
AB  - BACKGROUND: Graft survival depends on adequate immunosuppression. To evaluate the
      effect on the immune system of immunosuppressive therapies using calcineurin
      inhibitors (CNIs), several pharmacodynamic indices have been proposed to
      complement pharmacokinetic data. In this preliminary study we compared some of
      these parameters during combined immunosuppressant therapies. METHODS: We treated
      65 stable renal transplant recipients with cyclosporin A (CsA; n = 16),
      tacrolimus (TRL; n = 10); CsA + mycophenolate mofetil (MMF; n = 14); TRL + MMF (n
      = 13), and MMF (n = 12). Twelve nontreated healthy controls were also included.
      Calcineurin activity (CNA) in peripheral blood mononuclear cells was measured
      using (32)P-labeled peptide. Interleukin-2 (IL-2) and interferon-gamma production
      in phytohemagglutinin-activated whole blood were measured at 0 and 2 h postdose.
      The areas under the curves, c(min), c(max), and concentration at 2 h (c(2 h))
      were also measured. RESULTS: We found no differences in CNA between groups
      receiving CNIs alone or combined with MMF [median (25th-75th percentiles)]: CsA(2
      h), 3.87 (3.00-6.85)% alkaline phosphatase (AP); CsA+MMF(2 h), 3.90 (1.78-5.19)%
      AP; TRL(2 h), 5.68 (3.02-16.00)% AP; TRL+MMF(2 h), 11.80 (4.05-14.63)% AP. In
      vitro IL-2 production was significantly lower in the groups receiving combined
      therapy than in groups receiving CNIs alone [median (25th-75th percentiles)]:
      CsA(2 h), 276.52 (190.41-385.25) ng/L; CsA+MMF(2 h), 166.48 (81.06-377.01) ng/L
      (P <0.001); TRL(2 h), 249.34 (127.48-363.50) ng/L; TRL+ MMF(2 h), 122.13 (51.02
      180.00) ng/L (P <0.001). The correlations (r) between c(2 h) and CNA 2 h postdose
      were as follows: CsA, r = -0.74; CsA+MMF, r = -0.84; TRL, r = -0.70; TRL+ MMF, r
      = -0.70 (P <0.001 in all cases). CONCLUSIONS: The measurement of CNA may be of
      help in following the effect on the immune system of CNI treatments, even in
      combined therapies, but does not reflect the additional effect of MMF. In
      contrast, IL-2 in vitro production reflects the effect of both MMF and CNIs.

PMID- 14578323
TI  - Automated multicapillary electrophoresis for analysis of human serum proteins.
AB  - BACKGROUND: We evaluated a new, automated multicapillary zone electrophoresis
      (CE) instrument (Capillarys), 4.51 software version; Sebia) for human serum
      protein analysis. METHODS: With the Capillarys beta1-beta2+ reagent set, proteins
      were separated at 7 kV for 4 min in 15.5 cm x 25 micro m fused-silica capillaries
      (n = 8) at 35.5 degrees C in a pH 10 buffer with online detection at 200 nm.
      Serum samples with different electrophoretic patterns (n = 265) or potential
      interference (n = 69) were analyzed and compared with agarose gel electrophoresis
      (AGE; Hydrasys)-Hyrys, Hydragel protein(e) 15/30 reagent set; Sebia). RESULTS:
      CVs were <3.5% for albumin, <11% for alpha(1)-globulin, <4.1% for alpha(2)
      globulin, <7.4% for beta-globulin, and <5.8% for gamma-globulin (3 control
      levels); measured throughput was 60 samples/h. In patients without paraprotein (n
      = 116), the median differences between CE and AGE were -5.4 g/L for albumin, 4.0
      g/L for alpha(1)-globulin, 0.7 g/L for alpha(2)-globulin, 0.6 g/L for beta
      globulin (P <0.001 for all fractions), and -0.1 g/L for gamma-globulin (not
      significant). More samples had at least one gamma-migrating peak detected by CE
      (n = 135 vs 130; paraprotein detection limit, approximately 0.5-0.7 g/L), but
      fewer were quantified (n = 84 vs 91) because of gamma- to beta-migration shifts.
      There was a 1.2 g/L median difference between CE and AGE for gamma-migrating
      paraprotein quantification (n = 69; P <0.001). Several ultraviolet-absorbing
      substances (lipid emulsion, hemoglobin) or molecules (contrast agent, gelatin
      based plasma substitute) induced CE artifacts. CONCLUSIONS: The Capillarys
      instrument is a reliable CE system for serum protein analysis, combining
      advantages of full automation (ease of use, bar-code identification, computer
      assisted correction of alpha(1)-globulins) with high analytical performances and
      throughput.

PMID- 14578324
TI  - Two-dimensional mapping of copper and zinc in liver sections by laser ablation
      inductively coupled plasma mass spectrometry.
AB  - BACKGROUND: Metals are not homogeneously distributed in organ tissues. Although
      most mapping techniques, such as histologic staining methods, have been developed
      for element imaging on a subcellular level, many suffer from either low precision
      or poor detection limits. Therefore, small variations in elemental distribution
      cannot be identified. We developed a method for two-dimensional mapping of trace
      elements to identify the influence of metabolic zonation by the liver on trace
      element distribution. METHODS: A prepared homogeneous Certified Reference
      Material (CRM; LGC 7112, pig liver) was used to characterize the laser ablation
      inductively coupled plasma time-of-flight mass spectrometry (LA-ICP-MS) in terms
      of precision. Different isotopes for copper and zinc were monitored, and the use
      of carbon as an internal standard was investigated to correct for differences in
      ablation efficiency to identify the most precise mapping technique for liver
      samples. RESULTS: For the homogeneous CRM, the reproducibility of the copper and
      zinc signals was approximately 3-24% depending on spot size and number of pulses.
      When carbon was used as an internal standard, the reproducibility was improved
      significantly. Line scan signals over a length of 1.5 mm were more precise
      [relative SD (RSD), 1.6-6.1% for copper ((63)Cu, (65)Cu) and zinc ((64)Zn,
      (66)Zn) depending on the spot size, the scanning speed, and the element]. Thin
      section of sheep liver achieved precisions of 27-59% (raster scan) and 9-47%
      (line scan) RSD for copper, whereas the precision for zinc was significantly
      better: 8-18% (raster scan) and 4-21% (line scan) RSD. Long line scans and two
      dimensional element maps of the thin sections revealed the zonation of copper in
      sheep liver containing extremely low copper concentrations. CONCLUSION: Elemental
      mapping of trace elements generated by LA-ICP-MS can be very precise so that
      small changes in the elemental concentration in the tissue can be detected and
      nonuniform spatial distribution of the elements in tissues can be established.

PMID- 14578325
TI  - IgG subclass concentrations in certified reference material 470 and reference
      values for children and adults determined with the binding site reagents.
AB  - BACKGROUND: There is currently no international reference preparation for IgG
      subclass (IgGSc) quantification. This situation has led to calibration
      differences among assays and a variety of reference interval values with
      consequential difficulties in comparing results. We therefore evaluated IgGSc
      concentrations in Certified Reference Material 470 (CRM 470). METHODS: Pure,
      polyclonal IgG1, -2, -3, and -4 were prepared from a large serum pool for use as
      primary standards. The IgG mass in each preparation was calculated from amino
      acid analysis data. IgGSc concentrations were assessed in CRM 470 by nephelometry
      with modern analytical techniques, using these reference preparations.
      Subsequently, IgGSc concentrations were measured in 380 healthy individuals (250
      males and 130 females), and age-dependent reference intervals were established.
      RESULTS: IgGSc concentrations in CRM 470 were as follows: IgG1, 5028 mg/L; IgG2,
      3418 mg/L; IgG3, 579 mg/L, and IgG4, 381 mg/L, with a total IgG concentration of
      9406 mg/L, 2.83% below the certified total IgG value of 9680 mg/L. Age-dependent
      percentile curves for the four IgGSc were constructed using a Box-Cox
      transformation. Maximum median values were as follows: IgG1, 6.02 g/L at 11
      years; IgG2, 3.45 g/L at 31 years; IgG3, 0.63 g/L at 17 years; and IgG4, 0.48 g/L
      at 14 years. No significant sex-related differences were observed. CONCLUSIONS:
      The correlation between the summation of individual IgGSc and separate
      measurements of total IgG concentrations was good and supports the accuracy of
      the results. The results are based on The Binding Site assays and should not be
      considered appropriate for other assays unless so demonstrated.

PMID- 14578326
TI  - Serum carnosinase activity in plasma and serum: validation of a method and values
      in cardiopulmonary bypass surgery.

PMID- 14578327
TI  - Correction of urine cotinine concentrations for creatinine excretion: is it
      useful?

PMID- 14578328
TI  - Fetal nucleated erythrocytes in maternal circulation do not display a classic
      membrane-associated apoptotic characteristic (phosphatidylserine exposure)
      despite being positive by terminal dUTP nuclear end labeling.

PMID- 14578329
TI  - Haptoglobin gene subtyping by restriction enzyme analysis.

PMID- 14578330
TI  - Colorectal carcinoma susceptibility and metastases are associated with matrix
      metalloproteinase-7 promoter polymorphisms.

PMID- 14578331
TI  - Clinical evaluation of a reverse hybridization assay for the molecular detection
      of twelve MEFV gene mutations.

PMID- 14578332
TI  - Simple sequence-specific-primer-PCR method to identify the three main
      apolipoprotein E haplotypes.

PMID- 14578333
TI  - Genetic testing for familial Mediterranean fever in Austria by means of reverse
      hybridization teststrips.

PMID- 14578334
TI  - Stability of plasma free metanephrines during collection and storage as assessed
      by an optimized HPLC method with electrochemical detection.

PMID- 14578335
TI  - Use of magnetic beads for plasma cell-free DNA extraction: toward automation of
      plasma DNA analysis for molecular diagnostics.

PMID- 14578336
TI  - Effect of anticoagulants and cell separation media as preanalytical determinants
      on zymographic analysis of plasma matrix metalloproteinases.

PMID- 14578337
TI  - Measurement of immunoglobulin free light chains in serum.

PMID- 14578343
TI  - Phosphopeptide binding specificities of BRCA1 COOH-terminal (BRCT) domains.
AB  - Protein phosphorylation by protein kinases may generate docking sites for other
      proteins. It thus allows the assembly of signaling complexes in response to
      kinase activation. Several protein domains that bind phosphoserine or
      phosphothreonine residues have been identified, including the 14-3-3, PIN1, FHA,
      KIX, WD-40 domain, and polo box (Yaffe, M. B., and Elia, A. E. (2001) Curr. Opin.
      Cell Biol. 13, 131-138; Elia, A. E., Cantley, L. C., and Yaffe, M. B. (2003)
      Science 299, 1228-1231). The BRCA1 COOH-terminal (BRCT) domains are protein
      modules found in many proteins that regulate DNA damage responses (Koonin, E. V.,
      Altschul, S. F., and Bork, P. (1996) Nat. Genet. 13, 266-268). Whether BRCT
      domains can mediate phosphorylation-dependent interactions has not been
      systematically investigated. We report here that the BRCT domains also recognize
      phosphopeptides. Oriented peptide library analysis indicated that the BRCT
      domains from BRCA1, MDC1, BARD1, and DNA Ligase IV preferred distinct
      phosphoserine-containing peptides. In addition, the interaction between BRCA1 and
      the BRCT binding motif of BACH1 was required for BACH1 checkpoint activity.
      Furthermore, BRCT domains of the yeast DNA repair protein Rad9 could bind
      phosphopeptides, suggesting that the BRCT domains represent a class of ancient
      phosphopeptide-binding modules. Potential targets of BRCT domains were identified
      through data base search. Structural analysis of BRCA1 BRCT repeats also
      predicted conserved residues that may form the phosphopeptide-binding pocket.
      Thus, the BRCT repeats are a new family of phosphopeptide-binding domains in DNA
      damage responses.

PMID- 14578344
TI  - SecYEG proteoliposomes catalyze the Deltaphi-dependent membrane insertion of
      FtsQ.
AB  - In Escherichia coli, the insertion of most inner membrane proteins is mediated by
      the Sec translocase. Ribosome-bound nascent chains of Sec-dependent inner
      membrane proteins are targeted to the SecYEG complex via the signal recognition
      particle pathway. We now demonstrate that the signal recognition particle
      dependent co-translational membrane targeting and membrane insertion of FtsQ can
      be reconstituted with proteoliposomes containing purified SecYEG. SecA and a
      transmembrane electrical potential are essential for the translocation of the
      large periplasmic domain of FtsQ, whereas co-reconstituted YidC has an inhibitory
      effect. These data demonstrate that membrane protein insertion can be
      reconstituted with a minimal set of purified Sec components.

PMID- 14578345
TI  - Molecular basis for Kv1.5 channel block: conservation of drug binding sites among
      voltage-gated K+ channels.
AB  - Kv1.5 channels conduct the ultrarapid delayed rectifier current (IKur) that
      contributes to action potential repolarization of human atrial myocytes. Block of
      these channels has been proposed as a treatment for atrial arrhythmias. Here we
      report a novel and potent inhibitor of Kv1.5 potassium channels, N-benzyl-N
      pyridin-3-yl-methyl-2-(toluene-4-sulfonylamino)-benzamide hydrochloride
      (S0100176), which exhibits features consistent with preferential block of the
      open state. The IC50 of S0100176 for Kv1.5 expressed in Xenopus oocytes was 0.7
      microm. Ala-scanning mutagenesis within the pore helix and the S6 segment,
      regions that form the walls of the central cavity, was combined with voltage
      clamp analysis to identify point mutations that altered drug affinity. This
      approach identified Thr-479, Thr-480, Val-505, Ile-508, and Val-512 as the most
      important residues for block by S0100176. Mutations of these key residues to Ala
      or other amino acids caused marked changes in the IC50 of S0100176 (p<0.01). For
      example, the IC50 of S0100176 increased 362-fold for T480A, 26-fold for V505A,
      150-fold for I508A, and 99-fold for V512A. We used modeling to dock S0100176 into
      the inner cavity of a Kv1.5 pore homology model that was generated based on the
      crystal structure of KcsA. The docking predicted that the five residues
      identified by the Ala scan were positioned less than 4.5 A from the compound.
      Based on the homology models, the positions of the five amino acids identified to
      interact with S0100176 face toward the central cavity and overlap with putative
      binding sites for other blockers and voltage-gated potassium channels.

PMID- 14578346
TI  - Multivalent mechanism of membrane insertion by the FYVE domain.
AB  - Targeting of a wide variety of proteins to membranes involves specific
      recognition of phospholipid head groups and insertion into lipid bilayers. For
      example, proteins that contain FYVE domains are recruited to endosomes through
      interaction with phosphatidylinositol 3-phosphate (PtdIns(3)P). However, the
      structural mechanism of membrane docking and insertion by this domain remains
      unclear. Here, the depth and angle of micelle insertion and the lipid binding
      properties of the FYVE domain of early endosome antigen 1 are estimated by NMR
      spectroscopy. Spin label probes incorporated into micelles identify a hydrophobic
      protuberance that inserts into the micelle core and is surrounded by
      interfacially active polar residues. A novel proxyl PtdIns(3)P derivative is
      developed to map the position of the phosphoinositide acyl chains, which are
      found to align with the membrane insertion element. Dual engagement of the FYVE
      domain with PtdIns(3)P and dodecylphosphocholine micelles yields a 6-fold
      enhancement of affinity. The additional interaction of phosphatidylserine with a
      conserved basic site of the protein further amplifies the micelle binding
      affinity and dramatically alters the angle of insertion. Thus, the FYVE domain is
      targeted to endosomes through the synergistic action of stereospecific PtdIns(3)P
      head group ligation, hydrophobic insertion and electrostatic interactions with
      acidic phospholipids.

PMID- 14578347
TI  - Maintenance DNA methylation of nucleosome core particles.
AB  - The enzyme responsible for maintenance methylation of CpG dinucleotides in
      vertebrates is DNMT1. The presence of DNMT1 in DNA replication foci raises the
      issue of whether this enzyme needs to gain access to nascent DNA before its
      packaging into nucleosomes, which occurs very rapidly behind the replication
      fork. Using nucleosomes positioned along the 5 S rRNA gene, we find that DNMT1 is
      able to methylate a number of CpG sites even when the DNA major groove is
      oriented toward the histone surface. However, we also find that the ability of
      DNMT1 to methylate nucleosomal sites is highly dependent on the nature of the DNA
      substrate. Although nucleosomes containing the Air promoter are refractory to
      methylation irrespective of target cytosine location, nucleosomes reconstituted
      onto the H19 imprinting control region are more accessible. These results argue
      that although DNMT1 is intrinsically capable of methylating some DNA sequences
      even after their packaging into nucleosomes, this is not the case for at least a
      fraction of DNA sequences whose function is regulated by DNA methylation.

PMID- 14578348
TI  - Structural analysis of the reaction center light-harvesting complex I
      photosynthetic core complex of Rhodospirillum rubrum using atomic force
      microscopy.
AB  - The bacterium Rhodospirillum rubrum contains a simple photosynthetic system, in
      which the reaction center (RC) receives energy from the light-harvesting (LH1)
      complex. We have used high-resolution atomic force microscopy (AFM) to image two
      dimensional crystals of the RC-LH1 complex of R. rubrum. The AFM topographs show
      that the RC-LH1 complex is approximately 94 A in height, the RC-H subunit
      protrudes from the cytoplasmic face of the membrane by 40 A, and it sits 21 A
      above the highest point of the surrounding LH1 ring. In contrast, the RC on the
      periplasmic side is at a lower level than LH1, which protrudes from the membrane
      by 12 A. The RC-LH1 complex can adopt an irregular shape in regions of uneven
      packing forces in the crystal; this reflects a likely flexibility in the natural
      membrane, which might be functionally important by allowing the export of quinol
      formed as a result of RC photochemistry. Nanodissection of the RC by the AFM tip
      removes the RC-H subunit and reveals the underlying RC-L and -M subunits. LH1
      complexes completely lacking the RC were also found, providing ideal conditions
      for imaging both rings of LH1 polypeptides for the first time by AFM. In
      addition, we demonstrate the ellipticity of the LH1 ring at the cytoplasmic and
      periplasmic sides of the membrane, in both the presence and absence of the RC.
      These AFM measurements have been reconciled with previous electron microscopy and
      NMR data to produce a model of the RC-LH1 complex.

PMID- 14578349
TI  - Bone morphogenetic protein-1/Tolloid-like proteinases process dentin matrix
      protein-1.
AB  - Bone morphogenetic protein-1 (BMP-1)/Tolloid-like metalloproteinases play key
      roles in formation of mammalian extracellular matrix (ECM), through the
      biosynthetic conversion of precursor proteins into their mature functional forms.
      These proteinases probably play a further role in formation of bone through
      activation of transforming growth factor beta-like BMPs. Dentin matrix protein-1
      (DMP1), deposited into the ECM during assembly and involved in initiating
      mineralization of bones and teeth, is thought to undergo proteolysis in vivo to
      generate functional cleavage fragments found in extracts of mineralized tissues.
      Here, we have generated recombinant DMP1 and demonstrate that it is cleaved, to
      varying extents, by all four mammalian BMP-1/Tolloid-like proteinases, to
      generate fragments similar in size to those previously isolated from bone.
      Consistent with possible roles for the BMP-1/Tolloid-like proteinases in the
      physiological processing of DMP1, NH2-terminal sequences of products generated by
      BMP-1 cleavage of DMP1 match those predicted from processing at the predicted
      DMP1 site that shows greatest cross-species conservation of sequences. Moreover,
      fibroblasts derived from mouse embryos homozygous null for genes encoding three
      of the four mammalian BMP-1/Tolloid-like proteinases appear to be deficient in
      processing of DMP1. Thus, a further role for BMP-1-Tolloid-like proteinases in
      formation of mineralized tissues is indicated, via proteolytic processing of
      DMP1.

PMID- 14578350
TI  - Role of p38alpha Map kinase in Type I interferon signaling.
AB  - Multiple signaling pathways are activated during engagement of the Type I
      interferon (IFN) receptor to mediate biological responses, including the Jak-Stat
      and Rac1/p38 Map kinase signaling cascades. In the present study we sought to
      determine the functional relevance of the p38alpha isoform in IFN signaling,
      using cells from mouse embryos with targeted disruption of the p38alpha gene. Our
      data demonstrate that p38alpha activation is essential for Type I IFN-dependent
      transcriptional regulation via ISRE or GAS elements. On the other hand, the
      function of p38alpha is not required for IFN-dependent Ser727 or Tyr701
      phosphorylation of Stat1 and does not impact on the formation of ISGF3 or SIF
      nuclear binding complexes. In efforts to identify downstream effectors of p38
      that may mediate IFN-dependent transcriptional responses, we found that IFNalpha
      activates the kinase Msk1, a known regulator of histone phosphorylation and
      chromatin remodeling. In other studies, we demonstrate that Type I IFN-dependent
      activation of the kinases MapKapK-2 and MapKapK-3 is defective in the absence of
      p38alpha, while Type I IFN-dependent antiviral properties are decreased in cells
      with targeted disruption of the MapKapK-2 gene. Altogether, our data establish
      that the p38alpha Map kinase pathway regulates activation of downstream effectors
      that participate in the induction of IFN-dependent gene transcription, to mediate
      IFN-responses.

PMID- 14578351
TI  - Multiple and distinct effects of mutations of Tyr122, Glu123, Arg324, and Arg334
      involved in interactions between the top part of second and fourth transmembrane
      helices in sarcoplasmic reticulum Ca2+-ATPase: changes in cytoplasmic domain
      organization during isometric transition of phosphoenzyme intermediate and
      subsequent Ca2+ release.
AB  - We explored, by mutational substitutions and kinetic analysis, possible roles of
      the four residues involved in the hydrogen-bonding or ionic interactions found in
      the Ca2+-bound structure of sarcoplasmic reticulum Ca2+-ATPase, Tyr(122)
      Arg(324), and Glu(123)-Arg(334) at the top part of second transmembrane helix
      (M2) connected to the A domain and fourth transmembrane helix (M4) in the P
      domain. The observed substitution effects indicated that Glu(123), Arg(334), and
      Tyr(122) contributed to the rapid transition between the Ca2+-unbound and bound
      states of the unphosphorylated enzyme. Results further showed the more profound
      inhibitory effects of the substitutions in the M4/P domain (Arg(324) and
      Arg(334)) upon the isomeric transition of phosphorylated intermediate (EP) (loss
      of ADP sensitivity) and those in M2/A domain (Tyr(122) and Glu(123)) upon the
      subsequent processing and hydrolysis of EP. The observed distinct effects suggest
      that the interactions seen in the Ca2+-bound structure are not functionally
      important but indicate that Arg(334) with its positive charge and Tyr(122) with
      its aromatic ring are critically important for the above distinct steps. On the
      basis of the available structural information, the results strongly suggest that
      Arg(334) moves downward and forms new interactions with M2 (likely Asn(111)); it
      thus contributes to the inclination of the M4/P domain toward the M2/A domain,
      which is crucial for the appropriate gathering between the P domain and the
      largely rotated A domain to cause the loss of ADP sensitivity. On the other hand,
      Tyr(122) most likely functions in the subsequent Ca2+-releasing step to produce
      hydrophobic interactions at the A-P domain interface formed upon their gathering
      and thus to produce the Ca2+-released form of EP. During the Ca2+-transport
      cycle, the four residues seem to change interaction partners and thus contribute
      to the coordinated movements of the cytoplasmic and transmembrane domains.

PMID- 14578352
TI  - An ancient enzyme domain hidden in the putative beta-glucan elicitor receptor of
      soybean may play an active part in the perception of pathogen-associated
      molecular patterns during broad host resistance.
AB  - A successful defense against potential pathogens requires that a host organism is
      able to discriminate between self and nonself structures. Soybean (Glycine max
      L.) exploits a specific molecular pattern, a 1,6-beta-linked and 1,3-beta
      branched heptaglucoside (HG), present in cell walls of the oomycetal pathogen
      Phytophthora sojae, as a signal compound eliciting the onset of defense
      reactions. The specific and high affinity HG-binding site is contained in the
      beta-glucan-binding protein (GBP), which in turn is part of a proposed receptor
      complex. The ability to perceive and respond to Phytophthora cell wall-derived
      beta-glucan elicitors is exclusive to plants that belong to the Fabaceae.
      However, we propose that the presence of the GBP is essential, but not sufficient
      for beta-glucan elicitor-dependent disease resistance because genes encoding GBP
      related proteins can be retrieved from many plant species. Furthermore, we show
      that the GBP is composed of two different carbohydrateactive protein domains, one
      containing the beta-glucan-binding site, and the other related to glucan
      endoglucosidases of fungal origin. The glucan hydrolase displays most likely an
      endo-specific mode of action, cleaving only 1,3-beta-d-glucosidic linkages of
      oligoglucosides consisting of at least four moieties. Thus, the intrinsic endo
      1,3-beta-glucanase activity of the GBP is perfectly suited during initial contact
      with Phytophthora to release oligoglucoside fragments enriched in motifs that
      constitute ligands for the high affinity binding site present in the same
      protein. The concept of innate immunity in plants receives substantial support by
      this highly sophisticated system using ancient enzyme modules as an active part
      of the recognition mechanism.

PMID- 14578353
TI  - NADPH oxidase mediates lipopolysaccharide-induced neurotoxicity and
      proinflammatory gene expression in activated microglia.
AB  - Parkinson's disease is characterized by the progressive degeneration of
      dopaminergic neurons in the substantia nigra. We have previously reported that
      lipopolysaccharide (LPS)-induced degeneration of dopaminergic neurons is mediated
      by the release of proinflammatory factors from activated microglia. Here, we
      report the pivotal role of NADPH oxidase in inflammation-mediated neurotoxicity,
      where the LPS-induced loss of nigral dopaminergic neurons in vivo was
      significantly less pronounced in NADPH oxidase-deficient (PHOX-/-) mice when
      compared with control (PHOX+/+) mice. Dopaminergic neurons in primary
      mensencephalic neuron-glia cultures from PHOX+/+ mice were significantly more
      sensitive to LPS-induced neurotoxicity in vitro when compared with PHOX-/- mice.
      Further, PHOX+/+ neuron-glia cultures chemically depleted of microglia failed to
      show dopaminergic neurotoxicity with the addition of LPS. Neuron-enriched
      cultures from both PHOX+/+ mice and PHOX-/- mice also failed to show any direct
      LPS-induced dopaminergic neurotoxicity. However, the addition of PHOX+/+
      microglia to neuron-enriched cultures from either strain resulted in
      reinstatement of LPS-induced dopaminergic neurotoxicity, supporting the role of
      microglia as the primary source of NADPH oxidase-generated insult and
      neurotoxicity. Immunostaining for F4/80 in mensencephalic neuron-glia cultures
      revealed that PHOX-/- microglia failed to show activated morphology at 10 h,
      suggesting an important role of reactive oxygen species (ROS) generated from
      NADPH oxidase in the early activation of microglia. LPS also failed to elicit
      extracellular superoxide and produced low levels of intracellular ROS in
      microglia-enriched cultures from PHOX-/- mice. Gene expression and release of
      tumor necrosis factor alpha was much lower in PHOX-/- mice than in control
      PHOX+/+ mice. Together, these results demonstrate the dual neurotoxic functions
      of microglial NADPH oxidase: 1) the production of extracellular ROS that is toxic
      to dopamine neurons and 2) the amplification of proinflammatory gene expression
      and associated neurotoxicity.

PMID- 14578354
TI  - Incorporation of heterologous outer membrane and periplasmic proteins into
      Escherichia coli outer membrane vesicles.
AB  - Gram-negative bacteria shed outer membrane vesicles composed of outer membrane
      and periplasmic components. Since vesicles from pathogenic bacteria contain
      virulence factors and have been shown to interact with eukaryotic cells, it has
      been proposed that vesicles behave as delivery vehicles. We wanted to determine
      whether heterologously expressed proteins would be incorporated into the membrane
      and lumen of vesicles and whether these altered vesicles would associate with
      host cells. Ail, an outer membrane adhesin/invasin from Yersinia enterocolitica,
      was detected in purified outer membrane and in vesicles from Escherichia coli
      strains DH5alpha, HB101, and MC4100 transformed with plasmid-encoded Ail. In
      vesicle-host cell co-incubation assays we found that vesicles containing Ail were
      internalized by eukaryotic cells, unlike vesicles without Ail. To determine
      whether lumenal vesicle contents could be modified and delivered to host cells,
      we used periplasmically expressed green fluorescent protein (GFP). GFP fused with
      the Tat signal sequence was secreted into the periplasm via the twin arginine
      transporter (Tat) in both the laboratory E. coli strain DH5alpha and the
      pathogenic enterotoxigenic E. coli ATCC strain 43886. Pronase-resistant
      fluorescence was detectable in vesicles from Tat-GFP-transformed strains,
      demonstrating that GFP was inside intact vesicles. Inclusion of GFP cargo
      increased vesicle density but did not result in morphological changes in
      vesicles. These studies are the first to demonstrate the incorporation of
      heterologously expressed outer membrane and periplasmic proteins into bacterial
      vesicles.

PMID- 14578355
TI  - Probing protein-tyrosine phosphatase substrate specificity using a
      phosphotyrosine-containing phage library.
AB  - Protein tyrosine phosphatases (PTPs) play important, highly dynamic roles in
      signaling. Currently about 90 different PTP genes have been described. The
      enzymes are highly regulated at all levels of expression, and it is becoming
      increasingly clear that substrate specificity of the PTP catalytic domains proper
      contributes considerably to PTP functionality. To investigate PTP substrate
      selectivity, we have set up a procedure to generate phage libraries that presents
      randomized, phosphotyrosine-containing peptides. Phages that expressed suitable
      substrates were selected by immobilized, substrate-trapping GST-PTP fusion
      proteins. After multiple rounds of selection, positive clones were confirmed by
      SPOT analysis, dephosphorylation by wild-type enzyme, and Km determinations. We
      have identified distinct consensus substrate motifs for PTP1B, Sap-1, PTP-beta,
      SHP1, and SHP2. Our results confirm substrate specificity for individual PTPs at
      the peptide level. Such consensus sequences may be useful both for identifying
      potential PTP substrates and for the development of peptidomimetic inhibitors.

PMID- 14578356
TI  - Reactive oxygen species mediate virus-induced STAT activation: role of tyrosine
      phosphatases.
AB  - Respiratory syncytial virus (RSV) is the leading cause of epidemic respiratory
      tract illness in children in the United States and worldwide. RSV infection of
      airway epithelial cells induces formation of reactive oxygen species (ROS), whose
      production mediates the expression of cytokines and chemokines involved the
      immune/inflammatory responses of the lung. In this study, we have investigated
      the role of ROS in RSV-induced signal transducers and activators of transcription
      (STAT) activation and interferon regulatory factor (IRF) gene expression in human
      airway epithelial cells. Our results indicate that RSV replication induces IRF-1
      and -7 gene transcription, a response abrogated by antioxidants. RSV infection
      induces binding of STAT to the IRF-1 gamma-interferon-activated sequence (GAS)
      and IRF-7 interferon-stimulated responsive element (ISRE). STAT1 and STAT3 bind
      IRF-1 GAS, whereas STAT1, STAT2, IRF-1, and IRF-9 bind IRF-7 ISRE. Antioxidant
      treatment blocks RSV-induced STAT binding to both the IRF-1 GAS and IRF-7 ISRE by
      inhibition of inducible STAT1 and STAT3 tyrosine phosphorylation, suggesting that
      RSV-induced ROS formation is required for STAT activation and IRF gene
      expression. Although protein tyrosine phosphorylation is necessary for RSV
      induced STAT activation, Janus kinase and Src kinase activation do not mediate
      this effect. Instead, RSV infection inhibits intracellular tyrosine phosphatase
      activity, which is restored by antioxidant treatment. Pharmacological inhibition
      of tyrosine phosphatases induces STAT activation. Together, these results suggest
      that modulation of phosphatases could be an important mechanism of virus-induced
      STAT activation. Treatment of alveolar epithelial cells with the NAD(P)H oxidase
      inhibitor diphenylene iodonium abolishes RSV-induced STAT activation, indicating
      that NAD(P)H oxidase-produced ROS are required for downstream activation of the
      transcription factors IRF and STAT in virus-infected airway epithelial cells.

PMID- 14578357
TI  - Rho GTPases and phosphoinositide 3-kinase organize formation of branched
      dendrites.
AB  - Neurons receive information from other neurons via their dendritic tree.
      Dendrites and their branches result from alternating outgrowth and retraction.
      The Rho GTPases Rac and Cdc42 (cell division cycle 42) facilitate the outgrowth
      of branches, whereas Rho attenuates it. The mechanism of neurite retraction is
      unknown. Because the adenylyl cyclase activator forskolin causes numerous
      branched extensions in NG108-15 cells, we have investigated the underlying
      mechanism in this cell line. In additional studies, we used cultured hippocampal
      neurons in which forskolin induces branched dendrites. In both cell types,
      forskolin enhanced the activity of Cdc42, but not that of Rac, although both
      GTPases were necessary for the formation of branched extensions. Time lapse
      microscopy showed that forskolin did not increase the rate of addition of new
      extensions or branches, but it reduced the rate of the retraction so that more
      branched extensions persisted. Inhibition of phosphoinositide 3-kinase activity
      by wortmannin or LY294002 also reduced the rate of retraction and thus
      facilitated dendritic arborization. Forskolin diminished the activity of
      phosphoinositide 3-kinases. Inhibitors of phosphoinositide 3-kinases not only
      reduced the retraction but also the addition of new dendrites and branches. This
      reduction was no longer present when Rho kinase was simultaneously inactivated,
      suggesting an interaction of phosphoinositide 3-kinases and Rho kinase. The
      present results show a central role of phosphoinositide 3-kinases in dendrite
      formation. In neuronal cells, increased levels of cAMP can support dendritic
      arborization by modulating the activity of the lipid kinase.

PMID- 14578359
TI  - FKBP12-rapamycin-associated protein or mammalian target of rapamycin (FRAP/mTOR)
      localization in the endoplasmic reticulum and the Golgi apparatus.
AB  - FKBP12-rapamycin-associated protein (FRAP) or mammalian target of rapamycin
      (mTOR) and its effector proteins form a critical signaling pathway that regulates
      eukaryotic cell growth and proliferation. Although the protein components in this
      pathway have begun to be identified, little is known about their subcellular
      localization or the physiological significance of their localization. By
      immunofluorescence, we find that both endogenous and recombinant FRAP/mTOR
      proteins show localization predominantly in the endoplasmic reticulum (ER) and
      the Golgi apparatus. Consistent with this finding, FRAP/mTOR is cofractionated
      with calnexin, an ER marker protein. Biochemical characterization suggests that
      FRAP/mTOR is a peripheral ER/Golgi protein with tight membrane association.
      Finally, we have identified domains of FRAP/mTOR which may mediate its
      association with the ER and the Golgi apparatus.

PMID- 14578358
TI  - Differential role of protein kinase C delta isoform in agonist-induced dense
      granule secretion in human platelets.
AB  - Several platelet agonists, including thrombin, collagen, and thromboxane A(2),
      cause dense granule release independently of thromboxane generation. Because
      protein kinase C (PKC) isoforms are implicated in platelet secretion, we
      investigated the role of individual PKC isoforms in platelet dense granule
      release. PKCdelta was phosphorylated in a time-dependent manner that coincided
      with dense granule release in response to protease-activated receptor-activating
      peptides SFLLRN and AYPGKF in human platelets. Only agonists that caused platelet
      dense granule secretion activated PKCdelta. SFLLRN- or AYPGKF-induced dense
      granule release and PKCdelta phosphorylation occurred at the same respective
      agonist concentration. Furthermore, AYPGKF and SFLLRN-induced dense granule
      release was blocked by rottlerin, a PKCdelta selective inhibitor. In contrast,
      convulxin-induced dense granule secretion was potentiated by rottlerin but was
      abolished by Go6976, a classical PKC isoform inhibitor. However, SFLLRN-induced
      dense granule release was unaffected in the presence of Go6976. Finally,
      rottlerin did not affect SFLLRN-induced platelet aggregation, even in the
      presence of dimethyl-BAPTA, indicating that PKCdelta has no role in platelet
      fibrinogen receptor activation. We conclude that PKCdelta and the classical PKC
      isoforms play a differential role in platelet dense granule release mediated by
      protease-activated receptors and glycoprotein VI. Furthermore, PKCdelta plays a
      positive role in protease-activated receptor-mediated dense granule secretion,
      whereas it functions as a negative regulator downstream of glycoprotein VI
      signaling.

PMID- 14578360
TI  - Serum levels of the fetuin-mineral complex correlate with artery calcification in
      the rat.
AB  - The present studies were carried out to evaluate the possible association between
      the presence of the fetuin-mineral complex in serum and vitamin D-induced artery
      calcification. The first experiment shows that there is a fetuin-mineral complex
      in the blood of rats in which extensive calcification of the artery media has
      been induced by treatment with vitamin D for 96 h, and that there is no
      detectable fetuin-mineral complex in the blood of rats in which artery
      calcification has been inhibited by concurrent treatment with ibandronate or
      osteoprotegerin. The second experiment shows that the timing of vitamin D-induced
      artery calcification correlates with the timing of the maximal increase in serum
      fetuin-mineral complex levels. Whereas both results indicate that serum levels of
      the fetuin-mineral complex are indeed associated with vitamin D-induced artery
      calcification, the biochemical basis for this association is presently unclear.
      One possibility is that high levels of the fetuin-mineral complex cause defects
      in the ability of fetuin to prevent the growth of the mineral component, which
      then seeds artery calcification. Another possibility is that the fetuin-mineral
      complex is the downstream product of a pathway that begins with the true
      causative agent, and that the serum level of the fetuin-mineral complex is a
      marker for the activity of this agent in blood. An unexpected finding of the
      present studies is that vitamin D-induced artery calcification is also correlated
      with a 65 to 75% reduction in serum fetuin, a reduction that appears to be caused
      by the clearance of the fetuin-mineral complex from serum.

PMID- 14578361
TI  - Phosphatidylinositide 3-kinase priming couples c-FLIP to T cell activation.
AB  - Cellular FLICE (FADD-like interleukin-1-beta-converting enzyme)-inhibitory
      protein (c-FLIP) inhibits death receptor-induced apoptosis by binding to FADD
      (Fas-associated death domain protein) and pro-caspase-8. c-FLIP has also been
      shown to transmit activation signals and to enhance interleukin (IL)-2
      production. However, c-FLIP-mediated T cell activation is difficult to detect in
      most cells. We found that in DO11.10 T cells, c-FLIP expression led to inhibition
      of IL-2 production, in contrast to the readily detectable c-FLIP-induced
      activation in Jurkat cells. A direct comparison revealed that distinct signal
      pathways were regulated by c-FLIP in Jurkat cells and DO11.10 cells. We
      investigated whether constitutively activated phosphatidylinositide 3-kinase
      (PI3K) in Jurkat cells stimulated c-FLIP. Inhibition of PI3K in Jurkat cells
      abrogated a c-FLIP-mediated increase in IL-2 production. In addition, c-FLIP
      coordinated with active PI3K for ERK activation. Furthermore, introduction of
      PTEN back into Jurkat cells eliminated the stimulatory effect of c-FLIP on IL-2
      production and ERK activation. Our results suggest that priming with PI3K
      promotes the coupling of c-FLIP to T cell activation.

PMID- 14578363
TI  - Decreasing size of cardiogenic oscillations reflects decreasing compliance of the
      respiratory system during long-term ventilation.
AB  - Part of the energy produced by the heartbeat is transferred to the lung and
      promotes intrapulmonary gas mixing. It is likely that this transmission in the
      form of local mechanical disturbances affects and reflects respiratory mechanics.
      The effects of the cardiogenic oscillations were studied in seven piglets during
      7 h of monotonous mechanical ventilation. During the 1st h of ventilation, every
      heartbeat triggered a noticeable transient increase in lung volume of 14 ml (95%
      confidence interval = 10-17 ml). After 7 h, the increase in lung volume due to
      heartbeat significantly decreased to 7 ml (95% confidence interval = 2-9 ml, P <
      0.05). During the course of ventilation, overall lung compliance and gas exchange
      were progressively compromised. We conclude that 1) sufficient mechanical energy
      is transferred from the beating heart to the lung to increase lung volume, and 2)
      the ability of the heartbeats to help increase lung volume is reduced during long
      term ventilation, which reflects the changes in lung compliance.

PMID- 14578362
TI  - Muscle metabolism with blood flow restriction in chronic fatigue syndrome.
AB  - The purpose of this study was to determine whether chronic fatigue syndrome (CFS)
      is associated with reduced blood flow and muscle oxidative metabolism. Patients
      with CFS according to Centers for Disease Control criteria (n = 19) were compared
      with normal sedentary subjects (n = 11). Muscle blood flow was measured in the
      femoral artery with Doppler ultrasound after exercise. Muscle metabolism was
      measured in the medial gastrocnemius muscle with (31)P-magnetic resonance
      spectroscopy. Muscle oxygen saturation and blood volume were measured using near
      infrared spectroscopy. CFS and controls were not different in hyperemic blood
      flow or phosphocreatine recovery rate. Cuff pressures of 50, 60, 70, 80, and 90
      mmHg were used to partially restrict blood flow during recovery. All pressures
      reduced blood flow and oxidative metabolism, with 90 mmHg reducing blood flow by
      46% and oxidative metabolism by 30.7% in CFS patients. Hyperemic blood flow
      during partial cuff occlusion was significantly reduced in CFS patients (P <
      0.01), and recovery of oxygen saturation was slower (P < 0.05). No differences
      were seen in the amount of reduction in metabolism with partially reduced blood
      flow. In conclusion, CFS patients showed evidence of reduced hyperemic flow and
      reduced oxygen delivery but no evidence that this impaired muscle metabolism.
      Thus CFS patients might have altered control of blood flow, but this is unlikely
      to influence muscle metabolism. Furthermore, abnormalities in muscle metabolism
      do not appear to be responsible for the CFS symptoms.

PMID- 14578365
TI  - Effect of resistance training on skeletal muscle-specific force in elderly
      humans.
AB  - This study assessed muscle-specific force in vivo following strength training in
      old age. Subjects were assigned to training (n = 9, age 74.3 +/- 3.5 yr; mean +/-
      SD) and control (n = 9, age 67.1 +/- 2 yr) groups. Leg-extension and leg-press
      exercises (2 sets of 10 repetitions at 80% of the 5 repetition maximum) were
      performed three times/wk for 14 wk. Vastus lateralis (VL) muscle fascicle force
      was calculated from maximal isometric voluntary knee extensor torque with
      superimposed stimuli, accounting for the patella tendon moment arm length,
      ultrasound-based measurements of muscle architecture, and antagonist
      cocontraction estimated from electromyographic activity. Physiological cross
      sectional area (PCSA) was calculated from the ratio of muscle volume to fascicle
      length. Specific force was calculated by dividing fascicle force by PCSA.
      Fascicle force increased by 11%, from 847.9 +/- 365.3 N before to 939.3 +/- 347.8
      N after training (P < 0.05). Due to a relatively greater increase in fascicle
      length (11%) than muscle volume (6%), PCSA remained unchanged (pretraining: 30.4
      +/- 8.9 cm(2); posttraining: 29.1 +/- 8.4 cm(2); P > 0.05). Activation capacity
      and VL muscle root mean square electromyographic activity increased by 5 and 40%,
      respectively, after training (P < 0.05), indicating increased agonist neural
      drive, whereas antagonist cocontraction remained unchanged (P > 0.05). The VL
      muscle-specific force increased by 19%, from 27 +/- 6.3 N/cm(2) before to 32.1 +/
      7.4 N/cm(2) after training (P < 0.01), highlighting the effectiveness of
      strength training for increasing the intrinsic force-producing capacity of
      skeletal muscle in old age.

PMID- 14578364
TI  - Regulation of brain water during acute glucose-induced hyperosmolality in ovine
      fetuses, lambs, and adults.
AB  - We tested the hypothesis that, during acute glucose-induced hyperosmolality, the
      brain shrinks less than predicted on the basis of an ideal osmometer and that
      brain volume regulation is present in fetuses, premature and newborn lambs. Brain
      water responses to glucose-induced hyperosmolality were measured in the cerebral
      cortex, cerebellum, and medulla of fetuses at 60% of gestation, premature
      ventilated lambs at 90% of gestation, newborn lambs, and adult sheep. After
      exposure of the sheep to increases in osmolality with glucose plus NaCl, brain
      water and electrolytes were measured. The ideal osmometer is a system in which
      impermeable solutes do not enter or leave in response to an osmotic stress. In
      the absence of volume regulation, brain solute remains constant as osmolality
      changes. The osmotically active solute demonstrated direct linear correlations
      with plasma osmolality in the cerebral cortex of the fetuses at 60% of gestation
      (r = 0.72, n = 24, P = 0.0001), premature lambs (r = 0.58, n = 22, P = 0.005),
      newborn lambs (r = 0.57, n = 24, P = 0.004), and adult sheep (r = 0.70, n = 18, P
      = 0.001). Similar findings were observed in the cerebellum and medulla. Increases
      in the quantity of osmotically active solute over the range of plasma
      osmolalities indicate that volume regulation was present in the brain regions of
      the fetuses, premature lambs, newborn lambs, and adult sheep during glucose
      induced hyperosmolality. We conclude that, during glucose-induced
      hyperosmolality, the brain shrinks less than predicted on the basis of an ideal
      osmometer and exhibits volume regulation in fetuses at 60% of gestation,
      premature lambs, newborn lambs, and adult sheep.

PMID- 14578366
TI  - Opening the pericardium during pulmonary artery constriction improves cardiac
      function.
AB  - During acute pulmonary hypertension, both the pericardium and the right ventricle
      (RV) constrain left ventricular (LV) filling; therefore, pericardiotomy should
      improve LV function. LV, RV, and pericardial pressures and RV and LV dimensions
      and LV stroke volume (SV) were measured in six anesthetized dogs. The pericardium
      was closed, the chest was left open, and the lungs were held away from the heart.
      Data were collected at baseline, during pulmonary artery constriction (PAC), and
      after pericardiotomy with PAC maintained. PAC decreased SV by one-half. RV
      diameter increased, and septum-to-LV free wall diameter and LV area (our index of
      LV end-diastolic volume) decreased. Compared with during PAC, pericardiotomy
      increased LV area and SV increased 35%. LV and RV compliance (pressure-dimension
      relations) and LV contractility (stroke work-LV area relations) were unchanged.
      Although series interaction accounts for much of the decreased cardiac output
      during acute pulmonary hypertension, pericardial constraint and leftward septal
      shift are also important. Pericardiotomy can improve LV function in the absence
      of other sources of external constraint to LV filling.

PMID- 14578367
TI  - Cardiovascular response to arousal from sleep under controlled conditions of
      central and peripheral chemoreceptor stimulation in humans.
AB  - The cardiovascular response to an arousal occurring at the termination of an
      obstructive apnea is almost double that to a spontaneous arousal. We investigated
      the hypothesis that central plus peripheral chemoreceptor stimulation, induced by
      hypercapnic hypoxia (HH), augments the cardiovascular response to arousal from
      sleep. Auditory-induced arousals during normoxia and HH (>10-s duration) were
      analyzed in 13 healthy men [age 24 +/- 1 (SE) yr]. Subjects breathed on a
      respiratory circuit that held arterial blood gases constant, despite the
      increased ventilation associated with arousal. Arousals were associated with a
      significant increase in mean arterial blood pressure at 5 s (P < 0.001) and with
      a significant decrease in the R-R interval at 3 s (P < 0.001); however, the
      magnitude of the changes was not significantly different during normoxia compared
      with HH (mean arterial blood pressure: normoxia, 91 +/- 4 to 106 +/- 4 mmHg; HH,
      91 +/- 4 to 109 +/- 5 mmHg; P = 0.32; R-R interval: normoxia, 1.12 +/- 0.04 to
      0.90 +/- 0.05 s; HH, 1.09 +/- 0.05 to 0.82 +/- 0.03 [corrected] s; P = 0.78).
      Mean ventilation increased significantly at the second breath postarousal for
      both conditions (P < 0.001), but the increase was not significantly different
      between the two conditions (normoxia, 5.35 +/- 0.40 to 9.57 +/- 1.69 l/min; HH,
      8.57 +/- 0.63 to 11.98 +/- 0.70 l/min; P = 0.71). We conclude that combined
      central and peripheral chemoreceptor stimulation with the use of HH does not
      interact with the autonomic outflow associated with arousal from sleep to augment
      the cardiovascular response.

PMID- 14578368
TI  - Immediate exercise hyperemia in humans is contraction intensity dependent:
      evidence for rapid vasodilation.
AB  - We tested the hypothesis that rapid vasodilation proportional to contraction
      intensity contributes to the immediate (first cardiac cycle after initial
      contraction) exercise hyperemia. Ten healthy subjects performed single 1-s
      isometric forearm contractions at 5, 10, 15, 20, 30, 50, and 70% maximal
      voluntary contraction intensity (MVC) in arm above heart (AH) and below heart
      (BH) positions. Forearm blood flow (FBF; brachial artery mean blood velocity,
      Doppler ultrasound), mean arterial pressure (arterial tonometry), and heart rate
      (electrocardiogram) were measured beat by beat. Venous emptying (measured with a
      forearm strain gauge) was already maximized at 5% MVC, indicating that increases
      in contraction intensity did not further empty the forearm veins. Immediate
      increases in FBF were linearly proportional to contraction intensity from 5 to
      70% MVC in AH (slope = 4.4 +/- 0.5%DeltaFBF/%MVC). In BH, the immediate increase
      in FBF demonstrated a curvilinear relationship with increasing contraction
      intensity and was greater than AH at 15, 20, 30, and 50% MVC (P < 0.05). Peak
      changes in FBF were greater in BH vs. AH from 10 to 50% MVC, even when venous
      refilling was complete (P < 0.05). These data support the existence of a rapid
      acting vasodilatory mechanism(s) at the onset of human forearm exercise.

PMID- 14578369
TI  - Enhanced survival effect of pyruvate correlates MAPK and NF-kappaB activation in
      hydrogen peroxide-treated human endothelial cells.
AB  - We recently reported that pyruvate inhibited translocation and activation of p53
      caused by DNA damage due to oxidant injury (Lee YJ, Kang IJ, Bunger R, and Kang
      YH. Microvasc Res 66: 91-101, 2003); this was associated with increased
      expression of apoptosis-related bcl-2 and decreased expression of bax gene. This
      study attempted to delineate possible regulatory sites and mechanisms of
      antiapoptotic pyruvate, focusing on reactive oxygen species-mediated signaling in
      a human umbilical vein endothelial cell model. We compared the effects of the
      cytosolic reductant l-lactate and malate-aspartate shuttle blocker
      aminooxyacetate, both of which increase cytosolic NADH, on the downstream
      signaling pathway. Hydrogen peroxide (0.5 mM H2O2) depleted intracellular total
      glutathione that was prevented by pyruvate but not by l-lactate or
      aminooxyacetate. Activation of caspase-3 and the cleavage of procaspase-6 and
      procaspase-7 were strongly inhibited by pyruvate but markedly enhanced by l
      lactate and aminooxyacetate, implicating redox-related antiapoptotic mechanisms
      of pyruvate. Western blot analysis and immunochemical data revealed that H2O2
      induced transactivation of nuclear factor-kappaB (NF-kappaB) was also inhibited
      by pyruvate but not by l-lactate or aminooxyacetate. In addition, H2O2
      downregulated extracellular signal-regulated kinase (ERK1/2) and phosphorylated
      p38 mitogen-activated protein kinase (MAPK), effects that were fully reversed by
      pyruvate within 2 h. Collectively, these findings indicate that pyruvate can
      protect cellular glutathione, thus enhancing cellular antioxidant potential, and
      that enhanced antioxidant potential can desensitize NF-kappaB transactivation due
      to reactive oxygen species, suggesting possible metabolic redox relations to NF
      kappaB. Furthermore, pyruvate blocked the p38 MAPK pathway and activated the ERK
      pathway in an apparently redox-sensitive manner, which may regulate expression of
      genes believed to prevent apoptosis and promote cell survival. Thus pyruvate may
      have therapeutic potential for reducing endothelial dysfunction and improving
      survival during oxidative stress.

PMID- 14578370
TI  - Treatment with oxandrolone and the durability of effects in older men.
AB  - We investigated the effects of the anabolic androgen, oxandrolone, on lean body
      mass (LBM), muscle size, fat, and maximum voluntary muscle strength, and we
      determined the durability of effects after treatment was stopped. Thirty-two
      healthy 60- to 87-yr-old men were randomized to receive 20 mg oxandrolone/day (n
      = 20) or placebo (n = 12) for 12 wk. Body composition [dual-energy X-ray
      absorptiometry (DEXA), magnetic resonance imaging, and (2)H(2)O dilution] and
      muscle strength [1 repetition maximum (1 RM)] were evaluated at baseline and
      after 12 wk of treatment; body composition (DEXA) and 1-RM strength were then
      assessed 12 wk after treatment was discontinued (week 24). At week 12,
      oxandrolone increased LBM by 3.0 +/- 1.5 kg (P < 0.001), total body water by 2.9
      +/- 3.7 kg (P = 0.002), and proximal thigh muscle area by 12.4 +/- 8.4 cm(2) (P <
      0.001); these increases were greater (P < 0.003) than in the placebo group.
      Oxandrolone increased 1-RM strength for leg press by 6.7 +/- 6.4% (P < 0.001),
      leg flexion by 7.0 +/- 7.8% (P < 0.001), chest press by 9.3 +/- 6.7% (P < 0.001),
      and latissimus pull-down exercises by 5.1 +/- 9.1% (P = 0.02); these increases
      were greater than placebo. Oxandrolone reduced total (-1.9 +/- 1.0 kg) and trunk
      fat (-1.3 +/- 0.6 kg; P < 0.001), and these decreases were greater (P < 0.001)
      than placebo. Twelve weeks after oxandrolone was discontinued (week 24), the
      increments in LBM and muscle strength were no longer different from baseline (P >
      0.15). However, the decreases in total and trunk fat were sustained (-1.5 +/-
      1.8, P = 0.001 and -1.0 +/- 1.1 kg, P < 0.001, respectively). Thus oxandrolone
      induced short-term improvements in LBM, muscle area, and strength, while reducing
      whole body and trunk adiposity. Anabolic improvements were lost 12 wk after
      discontinuing oxandrolone, whereas improvements in fat mass were largely
      sustained.

PMID- 14578371
TI  - Impact of interrupted leptin pathways on ventilatory control.
AB  - Leptin deficiency in ob/ob mice produces marked depression of the hypercapnic
      ventilatory response, particularly during sleep. We now extend our previous
      findings to determine whether 1) leptin deficiency affects the hypoxic
      ventilatory response and 2) blockade of the downstream excitatory actions of
      leptin on melanocortin 4 receptors or inhibitory actions on neuropeptide Y (NPY)
      pathways has an impact on hypercapnic and hypoxic sensitivity. We have found that
      leptin-deficient ob/ob mice have the same hypoxic ventilatory response as weight
      matched wild-type obese mice. There were no differences in the hypoxic
      sensitivity between agouti yellow mice and weight-matched controls, or NPY
      deficient mice and wild-type littermates. Agouti yellow mice, with blocked
      melanocortin pathways, exhibited a significant depression of the hypercapnic
      sensitivity compared with weight-matched wild-type controls during non-rapid eye
      movement sleep (5.8 +/- 0.7 vs. 8.9 +/- 0.7 ml x min(-1) x %CO(2)(-1), P < 0.01),
      but not during wakefulness. NPY-deficient transgenic mice exhibited a small
      increase in the hypercapnic ventilatory response compared with wild-type
      littermates, but this was only present during wakefulness. We conclude that
      interruption of leptin pathways does not affect hypoxic sensitivity during sleep
      and wakefulness but that melanocortin 4 blockade is associated with depressed
      hypercapnic sensitivity in non-rapid eye movement sleep.

PMID- 14578372
TI  - Relative contributions of eyelid and eye-retraction motor systems to reflex and
      classically conditioned blink responses in the rabbit.
AB  - Early compensatory mechanisms between eyelid and eye-retraction motor systems
      following selective nerve and/or muscle lesions were studied in behaving rabbits.
      Reflex and conditioned eyelid responses were recorded in 1). controls and
      following 2). facial nerve section, 3). retractor bulbi muscle removal, and 4).
      facial nerve section and retractor bulbi muscle removal. Animals were classically
      conditioned with a delay paradigm by using a tone (350 ms, 600 Hz, 90 dB) as
      conditioned stimulus, followed 250 ms later by an air puff (100 ms, 3 kg/cm(2))
      as unconditioned stimulus. Conditioned eyelid responses generated in the absence
      of the facial motor system (i.e., by the almost sole action of the retractor
      bulbi motor system) presented a wavy profile, due to the succession of eye
      retraction movements. Learned eyelid responses generated in the absence of the
      eye-retraction motor system (i.e., by the almost exclusive action of the facial
      motor system) were similar to those of controls, but were reduced in amplitude
      and peak velocity. Finally, the isolated action of the extraocular recti muscle
      produced very small eyelid movements during both reflex and learned eyelid
      responses. Although each of these motor systems could act independently of the
      others, the motor result of their joint action did not coincide with the simple
      addition of their separate actions. Both facial and eye-retraction motor systems
      appear to be necessary for normal eyelid closure during blinking in rabbits.
      Central reorganization to compensate for loss of either of these systems may
      explain why the response of each system in isolation cannot be added linearly to
      obtain normal blink response magnitudes and profiles.

PMID- 14578373
TI  - Cardiovascular and respiratory responses to apneas with and without face
      immersion in exercising humans.
AB  - The effect of the diving response on alveolar gas exchange was investigated in 15
      subjects. During steady-state exercise (80 W) on a cycle ergometer, the subjects
      performed 40-s apneas in air and 40-s apneas with face immersion in cold (10
      degrees C) water. Heart rate decreased and blood pressure increased during
      apneas, and the responses were augmented by face immersion. Oxygen uptake from
      the lungs decreased during apnea in air (-22% compared with eupneic control) and
      was further reduced during apnea with face immersion (-25% compared with eupneic
      control). The plasma lactate concentration increased from control (11%) after
      apnea in air and even more after apnea with face immersion (20%), suggesting an
      increased anaerobic metabolism during apneas. The lung oxygen store was depleted
      more slowly during apnea with face immersion because of the augmented diving
      response, probably including a decrease in cardiac output. Venous oxygen stores
      were probably reduced by the cardiovascular responses. The turnover times of
      these gas stores would have been prolonged, reducing their effect on the oxygen
      uptake in the lungs. Thus the human diving response has an oxygen-conserving
      effect.

PMID- 14578374
TI  - Tyrosine 116 of the herpes simplex virus type 1 IEalpha22 protein is an ocular
      virulence determinant and potential phosphorylation site.
AB  - PURPOSE: To determine whether tyrosine 116 of the HSV-1 alpha22 protein is
      involved in virulence and is a potential phosphorylation site. METHODS: Site
      directed mutagenesis was used to revert the Y116C mutation in the alpha22 gene of
      the strain OD4 to wild type (C116Y), and the effect of virulence was tested by
      using a marker transfer-infection protocol in mice. Immunoblot analysis, tryptic
      phosphopeptide mapping, and phosphotyrosine pulldown-immunoblot protocols were
      used to assess the OD4 alpha22 isoforms. RESULTS: Reversion of the Y116C mutation
      resulted in a significant increase in the severity of ocular disease compared
      with the OD4 virus alone. Reversion of the Y116C and a previously identified
      mutation (S34A) together did not alter the severity of virulence compared with
      either mutation alone. Immunoblot analysis revealed a loss or reduction in
      alpha22 isoforms in the OD4 virus compared with wild type (CJ394 virus). The OD4
      virus had numerous alterations in the alpha22 tryptic phosphopeptide pattern,
      including loss of specific peptides and shifts in the position of several
      peptides. Phosphotyrosine pulldowns revealed a loss of one or more isoforms and
      shifts in the apparent size of others. CONCLUSIONS: The data indicate that Y116
      is a determinant of peripheral virulence in mice and that mutations at S34 and
      Y116 affect virulence independently. The data also show that the S34 and Y116
      mutations substantially alter phosphorylation of the alpha22 protein, that Y116
      is a potential phosphorylation site, and that the alpha22 protein contains at
      least two phosphotyrosines. These results are the first to show that mutation of
      a specific tyrosine in the alpha22 protein is associated with virulence.

PMID- 14578375
TI  - Identification and analysis of a novel mutation in the FOXC1 forkhead domain.
AB  - PURPOSE: To determine the genetic and biochemical defects that underlie Axenfeld
      Rieger malformations, identify the pathogenic mutation causing these
      malformations, and understand how these mutations alter protein function.
      METHODS: FOXC1 was amplified from a proband with Axenfeld-Rieger malformations
      and the proband's mother. PCR products were sequenced to identify the pathogenic
      mutation. Site-directed mutagenesis was used to introduce this mutation into the
      FOXC1 cDNA. A synthetic mutation at the same position was also introduced, and
      both natural and synthetic proteins were tested for their ability to localize to
      the nucleus, bind DNA, and transactivate gene expression. RESULTS: A novel
      missense mutation (L86F) was identified in FOXC1 in this family. The mutation is
      located in alpha-helix 1 of the forkhead domain. Biochemical assays showed that
      the L86F mutation does not affect nuclear localization of FOXC1, but reduces DNA
      binding and significantly reduces transactivation. The severity of the disruption
      to FOXC1 protein activity does not appear to correspond well with the severity of
      the phenotype in the patient. Analogous studies using a L86P, a known alpha-helix
      breaker, severely disrupts FOXC1 function, revealing the importance of helix 1 in
      FOXC1 structure and function. CONCLUSIONS: A novel mutation in helix 1 of the
      FOXC1 forkhead domain has been identified and the importance of position 86 in
      FOXC1 activity demonstrated. These studies also identified the role of helix 1 in
      FOXC1 function and provide further evidence for the lack of strong genotype
      phenotype correlation in FOXC1 pathogenesis. Normal development appears to be
      dependent on tight upper and lower thresholds of FOXC1 activity.

PMID- 14578376
TI  - Transcriptional regulation and expression of the dominant drusen gene FBLN3
      (EFEMP1) in mammalian retina.
AB  - PURPOSE: To determine the important transcriptional control elements and sites of
      expression of fibulin-3 in mammalian retina. METHODS: Sequencing and 5' rapid
      amplification of cDNA ends (RACE) were undertaken to characterize the genomic
      sequence upstream of the FBLN3 coding sequence. Reporter deletion-mutation
      constructs were used in luciferase transfection assays to determine the important
      regulatory motifs. Fibulin-3 expression in mouse and human retina was studied by
      in situ hybridization and RT-PCR. The effect of 17beta-estradiol on fibulin-3
      production was studied in COS-7 and ARPE-19 cells. RESULTS: Two untranslated
      exons were fully sequenced completing the characterization of FBLN3 that
      comprises 12 exons. Reporter assays suggest that the FBLN3 proximal promoter is
      contained within 425 bp upstream of exon 1. Important regulatory elements include
      three Sp1-binding sites, a Tant motif (trans-activating) and an estrogen response
      element (ERE) binding site (trans-repressing). No TATA or CAAT regulatory boxes
      were identified. RT-PCR suggests that the fibulin-3 gene is expressed in murine
      and human RPE, and in situ studies confirm that Fbln3 is expressed in the outer
      and inner nuclear layers, but strikingly not in the ganglion cell layer. Fibulin
      3 expression in ARPE-19 cells could be modified by varying the amount of estrogen
      in the cell culture medium. CONCLUSIONS: The 5' end of the FBLN3 gene has been
      characterized, and the important upstream motifs regulating its transcription
      have been identified. Fibulin-3 is expressed in adult retina and at early stages
      in human and mouse development. Estrogen may be an important regulator of fibulin
      3 expression, and this highlights a novel mechanism by which circulating estrogen
      may control the composition of the retinal extracellular matrix.

PMID- 14578377
TI  - Cone photoreceptor betagamma-transducin: posttranslational modification and
      interaction with phosducin.
AB  - PURPOSE: To characterize the structure of cone betagamma-transducin
      (Tbeta3gamma8) and its interaction with phosducin (pdc). METHODS: The Tgamma8
      subunit of Tbeta3gamma8 was isolated by column chromatography for peptide mapping
      with mass spectrometry. Tbeta3gamma8 was compared with rod betagamma-transducin
      (Tbeta1gamma1) in terms of the electrophoretic mobility, pdc binding affinity,
      and the effects of phosphorylation and methylation, and then the correlation to
      the crystal structures and functional domains of Tbeta1gamma1 was determined.
      RESULTS: The mature Tgamma8 is a 65-amino-acid peptide encoded by the Ggamma8
      gene with an acetylated and a farnesylated-methylated N- and C-terminus,
      respectively. Purified Tbeta3gamma8 is similar to Tbeta1gamma1 in that (1) both
      are heterogeneous, containing methylated and demethylated Tgamma subunits; (2)
      each demethylated dimer migrates faster than its methylated counterpart during
      native gel electrophoresis, and the methylation-associated mobility differential
      is masked by pdc binding; and (3) both dimers bind pdc with the same affinity,
      and the affinity is reduced threefold by PKA phosphorylation of pdc and twofold
      by demethylation at the C-terminus of Tgamma. Tbeta3gamma8 differs from
      Tbeta1gamma1 in exhibiting lower intrinsic electrophoretic mobility, and the
      difference is unaffected by either pdc binding or the status of Tgamma
      methylation. CONCLUSIONS: Tbeta3gamma8 is identical with Tbeta1gamma1 in Tgamma
      isoprenylation, the spatial organization, and the mode of pdc binding, indicating
      that its interaction with pdc does not play an important role in the
      specialization of cones. Changes in Tbetagamma characteristics by Tgamma
      methylation reveal conformational changes on a surface domain that is essential
      for Tbetagamma functions and support a regulatory role for reversible
      methylation.

PMID- 14578378
TI  - Refractive errors in an elderly Chinese population in Taiwan: the Shihpai Eye
      Study.
AB  - PURPOSE: Few epidemiologic data are available on refractive status in elderly
      Asians. The purpose of the study was to determine prevalence and risk factors
      associated with refractive errors in a metropolitan elderly Chinese population in
      Taiwan. METHODS: A population-based survey was conducted in the Shihpai district
      of Taipei, Taiwan. A total of 2045 residents aged 65 years or more were randomly
      selected and invited to complete a comprehensive questionnaire and undertake a
      detailed ocular examination, including best corrected visual acuity and
      measurements of refractive error, using autorefraction. Of the subjects, 1361
      (66.6%) participated in the ocular examination. Spherical equivalent (SE) was
      calculated in diopters (D), and data from right eyes were reported. RESULTS: The
      age- and sex-adjusted prevalence rates were determined for myopia (SE<-0.5 D,
      19.4%; SE<-1.0 D, 14.5%), high myopia (SE<-6.0 D, 2.4%), hyperopia (SE>+0.5 D,
      59.0%; SE>+1.0 D, 44.2%), astigmatism (cylinder<-0.5 D, 74.0%; cylinder<-1.0 D,
      45.3%), and anisometropia (SE difference between right and left eyes>0.5 D,
      45.2%; SE difference>1.0 D, 21.8%). The prevalence of myopia, astigmatism, and
      anisometropia significantly increased with age (all P<0.01). The prevalence of
      hyperopia tended to decrease with age. There was no gender difference in
      prevalence rates in any type of refractive error, except that women had a higher
      rate of hyperopia (SE>+1.0 D) than men (P=0.004). Multivariate regression
      analysis showed that myopia was weakly associated with higher educational level.
      The severity of lens nuclear opacity was positively associated with the rates of
      myopia and negatively associated with the rates of hyperopia. CONCLUSIONS: The
      prevalence of myopia in this elderly Chinese population is not much higher than
      in similarly aged elderly white populations, compared with a much greater
      difference in prevalence among younger Chinese versus white people. This suggests
      that changing environmental factors may account for the increased prevalence of
      myopia in younger cohorts of Chinese.

PMID- 14578379
TI  - Lens opacities in a rural population of southern India: the Aravind Comprehensive
      Eye Study.
AB  - OBJECTIVES: To determine the prevalence of lens opacities in an older population
      in rural southern India. METHODS: A cross-sectional study of 5150 persons aged 40
      years and more who were selected as part of a representative sample from three
      southern districts of the state of Tamil Nadu in southern India. All lenses were
      graded and classified for opacities and other disorders by slit lamp after
      pupillary dilation, using the Lens Opacification Classification System (LOCS) III
      and standard photographs. Definite cataract was defined as either LOCS III
      nuclear opalescence of grade 3.0 or more and/or cortical cataract of grade 3.0 or
      more and/or posterior subcapsular cataract (PSC) of grade 2.0 or more. RESULTS:
      Definite cataract was present in one or both eyes in 2499 (47.5%) of 5150
      subjects. The age-adjusted prevalence (adjusted to U.S. population estimates for
      2000) of definite cataract in this population was 61.9% (95% CI, 60.6-6.3). The
      prevalence was significantly lower in men (P=0.0002). In those eyes with
      cataracts, nuclear cataract (59.7%) was most common, and cortical cataract was
      present in 20.0% and PSC in 24.3%. Cataract surgery had been performed in 9.4%
      persons, including 3.0% who had bilateral surgery for cataracts. Best corrected
      visual acuity was less than 6/60 in 3.7% of aphakic eyes and in 0.8% of
      pseudophakic eyes. CONCLUSIONS: The higher age-adjusted prevalence and relatively
      early onset of age-related cataract in this population suggest that the cataract
      centered approach to minimizing preventable blindness, adopted by the National
      Program for Prevention of Blindness in India, is appropriate.

PMID- 14578380
TI  - Retinal vessel diameters and their associations with age and blood pressure.
AB  - PURPOSE: To describe the cross-sectional relationship between retinal arteriolar
      and venular diameters with age and blood pressure. METHODS: A population-based
      study was conducted in Beaver Dam, Wisconsin (n=4926, age range, 43-84 years).
      Retinal photographs of right eyes taken at the baseline examination (1988-90)
      were digitized. All arterioles and venules located in the area between one-half
      and one disc diameter from the optic disc margin were measured with a computer
      based program. These measurements were combined to provide the average diameters
      of retinal arterioles and venules of each eye, and the association with age and
      blood pressure (BP) was analyzed. RESULTS: After controlling for gender,
      hypertension, diabetes, serum glucose and lipids, cigarette smoking, and body
      mass index, retinal arteriolar diameters were found to be decreased by 2.1 microm
      (95% confidence interval [CI], 1.5-2.7) for each decade increase in age, and by
      4.4 microm (95% CI, 3.8-5.0) for each 10-mm Hg increase in mean arterial BP. The
      association of narrowed retinal arterioles and higher BP was stronger in younger
      persons. For each 10-mm Hg increase in mean arterial BP, arteriolar diameters
      decreased by 7.0 microm in persons aged 43 to 54 years but by only 2.5 microm in
      persons aged 75 to 84 years. In contrast, retinal venular diameters narrowed with
      increasing age but not with increasing BP. CONCLUSIONS: Retinal arteriolar
      diameters are narrower in older persons and in persons with higher BP,
      independent of other factors. The weaker association of retinal arteriolar
      diameters and BP in older people may reflect greater sclerosis of the retinal
      arterioles, preventing a degree of narrowing with higher BP similar to that seen
      in younger persons.

PMID- 14578381
TI  - Very long-term prognosis of patients with malignant uveal melanoma.
AB  - PURPOSE: To investigate the very long-term prognosis of patients with uveal
      melanoma and the clinical characteristics influencing it. METHODS: Charts,
      registry data, and histopathologic specimens of 289 consecutive patients with
      choroidal and ciliary body melanoma treated in the district of the Helsinki
      University Central Hospital, Finland, between 1962 and 1981 were audited.
      Definitions for coding the cause of death were adapted from the Collaborative
      Ocular Melanoma Study (COMS). Competing risks were taken into account by using
      cumulative incidence analysis and competing risks regression. RESULTS: Of the 289
      patients treated, 239 were deceased at the end of follow-up. The audited cause of
      death was uveal melanoma in 145 (61%) of them. The median follow-up of the 50
      survivors was 28 years. The original histopathologic diagnosis of metastasis and
      second cancer was correct in 91% of all specimens, but immunohistochemical
      reassessment changed 10% of biopsy and 7% of autopsy diagnoses. Of 45 positive
      autopsies, 18% were performed without suspicion of melanoma. Uveal melanoma
      related mortality was 31% (95% confidence interval [CI], 26-37) by 5 years, 45%
      (95% CI, 40-51) by 15 years, 49% (95% CI, 43-55) by 25 years, and 52% (95% CI, 45
      58) by 35 years, according to cumulative incidence analysis. Of patients who died
      of uveal melanoma, 62%, 90%, 98%, and 100% did so within 5, 15, 25, and 35 years,
      respectively. Between 15 and 35 years, 20% to 33% of deaths were still due to
      uveal melanoma. By competing risks regression analysis, the hazard ratio was 1.08
      (P=0.0012) for each millimeter increase in tumor diameter, 2.27 (P=0.0076) for
      extraocular growth, and 1.89 (P=0.0011) for ciliary body involvement.
      CONCLUSIONS: Metastatic uveal melanoma was the leading single cause of death
      throughout the study. Cumulative incidences provide a sound basis for patient
      counseling and design of trials.

PMID- 14578382
TI  - Dose fractionation effects in primary and metastatic human uveal melanoma cell
      lines.
AB  - PURPOSE: To investigate the effects of split-dose irradiation on primary and
      metastatic uveal melanoma cell lines, with a clonogenic survival assay. METHODS:
      Appropriate cell concentrations of four primary and four metastatic human uveal
      melanoma cell lines were cultured for irradiation with single doses and with two
      equal fractions separated by 5 hours. After irradiation, colony formation was
      allowed for 7 to 21 days. Two cutaneous melanomas were also tested for
      comparison. All survival curves were analyzed using the linear quadratic (LQ)
      model. Specific parameters for the intrinsic radiosensitivity (alpha-component,
      SF2), for the capacity of repair of DNA damage (beta-component), as well as the
      alpha/beta ratio were calculated. RESULTS: After single-dose irradiation a wide
      range in the values of the alpha- and beta-component was obtained for both
      primary and metastatic uveal melanomas, which resulted in a wide range of
      alpha/beta ratios. In contrast, calculations based on split-dose data, with which
      the beta-component could be estimated independent of the alpha-component,
      indicated that estimates for the capacity of sublethal DNA damage repair was very
      similar in all cell lines. This indicated that intrinsic factors dominated the
      radiosensitivity of these cell lines. Split-dose irradiation had little influence
      on the intrinsic radiosensitivity (alpha-component), but cell survival increased
      for all cell lines. For the two cutaneous melanomas comparable split-dose results
      were obtained. CONCLUSIONS: For both primary and metastatic uveal melanoma cell
      lines, data from single and fractionated doses indicate large variations in
      radiosensitivity, which are mainly dominated by the intrinsic radiosensitivities.
      Doses of approximately 8 Gy in five fractions would be sufficient to eradicate
      10(9) cells (approximately 1 cm3) of the most radioresistant tumor cell lines,
      but this schedule is an overkill for the radiosensitive tumor cell lines. Based
      on specific morphologic and histologic tumor markers, more individualized dose
      fractionation schedules could improve the therapeutic ratio for uveal melanomas.

PMID- 14578383
TI  - The effect of posterior capsule opacification on visual function.
AB  - PURPOSE: To investigate how posterior capsule opacification (PCO) affects visual
      function in pseudophakic eyes. METHODS: One hundred and six eyes that had
      undergone uncomplicated phacoemulsification were recruited sequentially. Patients
      with surgical complications or other ocular disease were excluded. PCO was
      assessed by a digital retroillumination camera using a software program based on
      the analysis of texture in the image, and the percentage area within the central
      3-mm zone of the posterior capsule was calculated. Visual function assessment
      included Early Treatment Diabetic Retinopathy Study (ETDRS) high- and low
      contrast visual acuity, contrast sensitivity with the Pelli-Robson and CSV-1000
      grating charts, and forward light-scatter by the direct-compensation method (van
      den Berg). RESULTS: The percentage PCO required for decline in high-contrast
      ETDRS was 78%; for low-contrast acuity and Pelli-Robson, 46%; for CSV-1000
      contrast sensitivity, 38% to 51%; and for forward light-scatter, less than 1%
      PCO. CONCLUSIONS: Central PCO affects psychophysical test results with differing
      degrees of sensitivity. Forward light-scatter is the most sensitive, followed by
      contrast sensitivity and visual acuity.

PMID- 14578384
TI  - Postural stability changes in the elderly with cataract simulation and refractive
      blur.
AB  - PURPOSE: To determine the influence of cataractous and refractive blur on
      postural stability and limb-load asymmetry (LLA) and to establish how postural
      stability changes with the spatial frequency and contrast of the visual stimulus.
      METHODS: Thirteen elderly subjects (mean age, 70.76 +/- 4.14 [SD] years) with no
      history of falls and normal vision were recruited. Postural stability was
      determined as the root mean square [RMS] of the center of pressure (COP) signal
      in the anterior-posterior (A-P) and medial-lateral directions and LLA was
      determined as the ratio of the average body weight placed on the more-loaded limb
      to the less-loaded limb, recorded during a 30-second period. Data were collected
      under normal standing conditions and with somatosensory system input disrupted.
      Measurements were repeated with four visual targets with high (8 cyc/deg) or low
      (2 cyc/deg) spatial frequency and high (Weber contrast, approximately 95%) or low
      (Weber contrast, approximately 25%) contrast. Postural stability was measured
      under conditions of binocular refractive blur of 0, 1, 2, 4, and 8 D and with
      cataract simulation. The data were analyzed in a population-averaged linear
      model. RESULTS: The cataract simulation caused significant increases in postural
      instability equivalent to that caused by 8-D blur conditions, and its effect was
      greater when the input from the somatosensory system was disrupted. High spatial
      frequency targets increased postural instability. Refractive blur, cataract
      simulation, or eye closure had no effect on LLA. CONCLUSIONS: Findings indicate
      that cataractous and refractive blur increase postural instability, and show why
      the elderly, many of whom have poor vision along with musculoskeletal and central
      nervous system degeneration, are at greater risk of falling. Findings also
      highlight that changes in contrast sensitivity rather than resolution changes are
      responsible for increasing postural instability. Providing low spatial frequency
      information in certain environments may be useful in maintaining postural
      stability. Correcting visual impairment caused by uncorrected refractive error
      and cataracts could be a useful intervention strategy to help prevent falls and
      fall-related injuries in the elderly.

PMID- 14578385
TI  - Zernike polynomial fitting fails to represent all visually significant corneal
      aberrations.
AB  - PURPOSE: It is assumed that wavefront error data arising from aberrometry are
      adequately described by a Zernike polynomial function, although this assumption
      has not been extensively tested. Inaccuracies in wavefront error may compromise
      clinical testing and refractive correction procedures. The current retrospective
      study correlates visual acuity with corneal wavefront error and with the residual
      surface elevation error after fitting with the Zernike method. METHODS: Corneal
      topography maps were obtained from 32 keratoconus cases, 27 postoperative
      penetrating keratoplasty cases, and 29 postoperative conductive keratoplasty
      cases (88 total). The best spectacle-corrected visual acuity (BSCVA) for each
      case ranged from -0.2 to 1.3 logarithm of the minimum angle of resolution
      (logMAR) units (20/12.5-20/400). Topography was analyzed to determine wavefront
      error and the elevation fit error for a 4-mm optical zone. The 4th and 10th
      expansion series were analyzed with the 0th-order (piston) and 1st order (tip and
      tilt) removed. Linear regression analysis was performed. The difference in root
      mean square (RMS) error between the 4th- and 10th-order analyses was assessed for
      both wavefront and elevation fit error. RESULTS: The correlation of BSCVA to
      wavefront error for 4th-order terms was moderately strong and significant
      (R2=0.581; P<0.001). The 10th-order correlation for wavefront error had a similar
      result (R2=0.565; P<0.001), but the regression was not significantly different
      from the 4th-order result. The correlation of BSCVA to the elevation fit error
      was strong and significant for the 4th order (R2=0.658; P<0.001). The 10th-order
      data had a similar result (R2=0.509; P<0.001), and there was no significant
      difference between the two regressions. Only 72% of the cases showed a shift
      toward increased wavefront error with the 10th-order series, whereas 18% lost
      wavefront error. All cases showed a shift toward improved elevation fit with the
      10th-order expansion. CONCLUSIONS: The wavefront error correlation to acuity was
      moderately strong, but the corneal elevation fit error also strongly correlated
      with visual acuity, indicating that Zernike polynomials do not fully characterize
      the surface shape features that influence vision and that exist in postsurgical
      or pathologic eyes. In addition, the change in wavefront error when using a
      larger expansion series was found to increase or diminish somewhat unpredictably.
      The authors conclude that Zernike polynomials fail to model all the information
      that influences visual acuity, which may confound clinical diagnosis and
      treatment.

PMID- 14578386
TI  - Protective effect of D-beta-hydroxybutyrate on corneal epithelia in dry eye
      conditions through suppression of apoptosis.
AB  - PURPOSE: To investigate the effect of D-beta-hydroxybutyrate (HBA) on ocular
      surface epithelial disorders induced by tear fluid deficiency, the potency of HBA
      and serum, the efficacy of which has been well documented in clinical
      application, were compared. METHODS: Rat corneal epithelial erosion was induced
      by exposure of rat eyes to continuous low-humidity airflow, which accelerated the
      tear evaporation. During desiccation, one eye of each rat was treated with HBA
      (20, 40, or 80 mM) or rat serum (5%, 20%, or 100%), and in the other eye a drop
      of phosphate-buffered saline (PBS) was instilled as the control. Histopathologic
      examination and quantification of the epithelial defect area were performed. The
      apoptosis in the epithelia was determined by chromatin condensation using the
      Hoechst 33342 fluorescein probe. RESULTS: In PBS-treated eyes, thinning in the
      cell layer was seen on the periphery of the initial wound after 6 hours, and it
      progressed to defects after 12 hours. In the 80-mM HBA and 20% serum
      applications, the pathologic change in the epithelia was moderate, and the
      structure was maintained in an almost normal state in the 100% serum application.
      Significant decreases in the defect areas were observed in the 5%, 20%, and 100%
      serum and 40- and 80-mM HBA treatment groups compared with the PBS-treated eyes
      (n=12). A significant suppression of chromatin condensation was observed with HBA
      and serum treatment. CONCLUSIONS: These results suggest the potential clinical
      application of HBA for ocular surface epithelial disorders to maintain epithelial
      cell viability in patients with dry eye.

PMID- 14578387
TI  - Expression of CD34 and L-selectin on human corneal keratocytes.
AB  - PURPOSE: To investigate the expression of CD34, a hematopoietic stem cell marker
      and an adhesion molecule, and its ligand L-selectin in the human cornea. METHODS:
      Seventeen normal adult human corneal specimens were studied by
      immunohistochemistry using a panel of monoclonal antibodies against all three
      classes of the hematopoietic stem cell marker CD34 and its ligand L-selectin. An
      additional six corneal specimens were used for protein extraction and analysis by
      Western blotting, using the CD34 and L-selectin antibodies. PCR was used to
      determine expression of mRNA for CD34 and L-selectin in the corneal specimens.
      RESULTS: Only corneal keratocytes showed positive immunostaining for all three
      classes of CD34. Western blotting confirmed the expression of CD34 by these cells
      and mRNA expression for CD34 in the corneal stroma was demonstrated by PCR. For L
      selectin, positive staining around keratocytes was noted on immunohistochemistry
      but L-selectin could not be detected either by Western blotting or PCR.
      CONCLUSIONS: Normal human corneal keratocytes express all three classes of CD34.
      The expression of this adhesion molecule on corneal keratocytes suggests that it
      may have a role in keeping the keratocytes anchored in their microniche, between
      the collagen lamellae. The positive staining for L-selectin found by
      immunohistochemistry but not by Western blotting or PCR would indicate the
      presence of either another ligand from the selectin family or a cross-reactive
      epitope on corneal keratocytes.

PMID- 14578388
TI  - Computer-synthesis of an interference color chart of human tear lipid layer, by a
      colorimetric approach.
AB  - PURPOSE: To synthesize an interference color chart for the specific tear lipid
      layer interference camera, DR-1, for the conversion of the tear film lipid layer
      thickness into color graphic information--that is, for the quantification of the
      tear interference image--by a colorimetric approach. METHODS: Because the color
      of the tear lipid layer interference image is visualized by a white light source
      interference phenomena, to produce gamma-corrected red, green, and blue (RGB)
      values of a specific interference color at a certain tear lipid film thickness,
      XYZ tristimulus values of the Commission Internationale de l'Eclairage (CIE) were
      obtained. XYZ tristimulus values were calculated from the light source spectrum
      of the DR-1 camera, the color-matching function of CIE, and the reflectance of
      the tear interference image in wavelengths ranging from 380 to 780 nm. These
      calculated interference colors were synthesized ranging from 0 nm to 1000 nm of
      lipid film thickness to produce a color chart. The applicability of the new color
      chart in the analysis of the lipid layer thickness was tested on a healthy
      control subject with normal tear function and a patient with dry eye who had
      aqueous tear deficiency and meibomian gland obstruction. RESULTS: The specific
      tear interference color chart for the DR-1 camera was obtained with RGB and XYZ
      tristimulus values. The interference chart ranged from 0 to approximately the 5th
      interference order. The interference colors from clinical DR-1 images could be
      converted to lipid thickness data by using the color chart system. CONCLUSIONS: A
      new tear interference color chart was developed in this study, which may be of
      benefit in converting tear interference color information to data describing the
      thickness of the tear film lipid layer.

PMID- 14578389
TI  - Propagation and phenotypic preservation of rabbit limbal epithelial cells on
      amniotic membrane.
AB  - PURPOSE: To describe the phenotypic characteristics of a limbal epithelial cell
      sheet outgrowth from a limbal explant cultured on amniotic membrane. METHOD:
      Immunofluorescent staining and confocal microscopy were used to examine the
      expressions of p63, Ki-67, keratins 3 and 14, connexin 43, and the integrin
      alpha6/beta4 and alpha3/beta1 subunits in corneal and limbal tissues in a limbal
      explant and epithelial outgrowth cultured for 2 weeks on amniotic membrane.
      RESULTS: The expression patterns of p63, Ki-67, keratins, integrins, and connexin
      43 in a limbal explant with an epithelial outgrowth cultured for 2 weeks on
      amniotic membrane resembled those in freshly prepared limbus. Moreover, the
      distribution of integrin subunits in positive cells of the limbal explant and its
      epithelial outgrowth was similar to that of the corneal epithelial cells during
      wound repair. CONCLUSIONS: The epithelial cell sheet grown from a limbal explant
      on amniotic membrane exhibited a phenotype similar to that of the limbus,
      suggesting that amniotic membrane is a substrate capable of supporting the
      propagation and preservation of p63-positive limbal epithelial cells.

PMID- 14578391
TI  - Pinin/DRS/memA interacts with SRp75, SRm300 and SRrp130 in corneal epithelial
      cells.
AB  - PURPOSE: Pinin (Pnn/DRS/memA) is a cell-adhesion-related and nuclear protein that
      has been identified as central in the establishment and maintenance of corneal
      epithelial cell-cell adhesion. To begin the elucidation of the role of Pnn within
      the nucleus of corneal epithelial cells, this study was undertaken to identify
      the proteins that bind to Pnn. METHODS: Yeast two-hybrid analyses were performed.
      A human cDNA library in the pGAD-10 vector and C-terminal region of human Pnn
      (465-717) in a pAS2-1 vector were cotransformed into the PJ69-4A yeast strain,
      containing the lacZ, HIS3, and ADE2 reporter genes. To dissect domains of Pnn
      responsible for mediating the interaction with the identified proteins, PNN
      fragments were ligated with the DNA-binding domain of the pAS2-1 vector. Human
      corneal epithelial cells (HCE-T, RCB1384) and HEK-293 cells were cotransfected
      with mammalian expression vectors containing Pnn with identified interacting
      partners and subsequently immunostained and immunoblotted to determine expressed
      and endogenous proteins. RESULTS: Pnn colocalized and copurified with serine
      arginine (SR) proteins. Three SR-rich proteins were identified that interact with
      the C-terminus of Pnn: SRp75 and SRm300, known components of spliceosome
      machinery, and a novel 130-kDa nuclear protein, SRrp130. All of these proteins
      colocalized and coimmunoprecipitated with one another and exhibited speckled
      nuclear distribution that aligned with components of the pre-mRNA splicing
      machinery. The cDNA for SRrp130 encoded a protein of 805 amino acid residues and
      contained multiple arginine-serine (RS) repeats but had no RNA recognition motif.
      Analysis of the Pnn motifs using two-hybrid system assays demonstrated that the
      polyserine/RS motif within Pnn plays a central but not exclusive role in
      mediating molecular interactions with identified SR-rich proteins. CONCLUSIONS:
      The results suggest that Pnn and SR-rich proteins may be part of a multiprotein
      complex within the nucleus and may be involved in pre-mRNA processing.

PMID- 14578390
TI  - UVB-elicited induction of MMP-1 expression in human ocular surface epithelial
      cells is mediated through the ERK1/2 MAPK-dependent pathway.
AB  - PURPOSE: Pterygia are common, frequently recurring ocular surface lesions
      characterized by tissue remodeling, cellular proliferation, angiogenesis, and
      inflammation. The increased incidence of pterygia in persons exposed to excessive
      solar radiation suggests that ultraviolet (UV) light may play a critical role in
      the pathogenesis of this disease. These investigations were focused on the
      expression of collagenase-1 (matrix metalloproteinase [MMP]-1) in pterygia and
      cultured pterygium epithelial cells, to determine whether the expression of this
      protease could be modified after exposure to UVB. METHODS: Pterygium,
      conjunctival, and limbal epithelial cells were subcultured and exposed to various
      amounts of UVB. The conditioned medium and RNA were harvested for analysis by
      gelatin zymography, Western blot analysis, ELISA, and RT-PCR. Furthermore, whole
      pterygium specimens were irradiated to determine secreted MMP-1 levels. RESULTS:
      Immunohistochemical analysis revealed enhanced MMP-1 expression in pterygia that
      corresponded precisely with p63-positive epithelial cells. In contrast,
      significantly less MMP-1 reactivity was found in normal conjunctiva, limbus, and
      cornea. A dose- and time-dependent increase in MMP-1 was observed when pterygium
      epithelial cells were exposed to UVB with no significant modulation of inhibitor
      activity. MMP-1 was not affected in irradiated normal conjunctival epithelial
      cells or in pterygium fibroblasts but was induced in limbal epithelial cells.
      Although the induction of MMP-1 after UVB was not mediated by an intermediate
      soluble factor, the extracellular signal-regulated kinase (ERK)1/2 mitogen
      activated protein kinase (MAPK) intracellular pathway was involved. CONCLUSIONS:
      Collectively, these data support the hypothesis of the involvement of UV light
      and MMPs in the development of pterygia and may assist in devising new
      therapeutic approaches for the treatment and prevention of pterygia.

PMID- 14578392
TI  - Modulation of corneal fibroblast contractility within fibrillar collagen
      matrices.
AB  - PURPOSE: To investigate the migratory and contractile behavior of isolated human
      corneal fibroblasts in fibrillar collagen matrices. METHODS: A telomerase
      infected, extended-lifespan human corneal fibroblast cell line (HTK) was
      transfected by using a vector for enhanced green fluorescent protein (GFP)-alpha
      actinin. Cells were plated at low density on top of or within 100-microm-thick
      fibrillar collagen lattices. After 18 hours to 7 days, time-lapse imaging was
      performed. At each 1- to 3-minute interval, GFP and Nomarski differential
      interference contrast (DIC) images were acquired in rapid succession. Serum
      containing (S+) medium was used initially for perfusion. After 2 hours, perfusion
      was switched to either serum-free (S-) or S+ medium containing the Rho-kinase
      inhibitor Y-27632 for 1 to 2 hours. Finally, perfusion was changed back to S+
      medium for 1 hour. RESULTS: Two to 4 days after plating, many cells underwent
      spontaneous contraction and/or relaxation in S+ medium. A decrease in the
      distance between consecutive alpha-actinin-dense bodies along stress fibers was
      measured during contraction, and focal adhesion and matrix displacements
      correlated significantly. Removal of serum or inhibition of Rho-kinase induced
      cell body elongation and relaxation of matrix stress, as confirmed using finite
      element modeling. Rapid formation and extension of pseudopodia and filopodia were
      also observed, and transient tractional forces were generated by these extending
      processes. CONCLUSIONS: Cultured human corneal fibroblasts can undergo rapid
      changes in the subcellular pattern of force generation that are mediated, in
      part, by Rho-kinase. Sarcomeric shortening of stress fibers in contracting
      corneal fibroblasts is also demonstrated for the first time.

PMID- 14578393
TI  - Th2-biased immune system promotion of allogeneic corneal epithelial cell survival
      after orthotopic limbal transplantation.
AB  - PURPOSE: The Th2-biased immune system can promote penetrating keratoplasty
      survival in mice. A series of experiments were performed to determine whether
      this system could prolong corneal limbal transplant (LT) survival. METHODS:
      BALB/c (H-2d) mice were immunized with 50 microg of keyhole limpet hemocyanin
      (KLH) in incomplete Freud's adjuvant. Four weeks later, the corneal epithelium,
      including the limbal area, was removed, and the mice received LT from B10.D2 (H
      2d), C57BL/10 (H-2b), or enhanced green fluorescence protein (EGFP) transgenic (H
      2b) donor mice. Immediately thereafter, recipient mice were immunized with 50
      micro g of KLH or Hanks' balanced salt solution (HBSS; control) in complete
      Freund's adjuvant. The allograft fates were assessed clinically. Lymphocytes of
      recipients were examined for donor-specific proliferation and for donor-specific
      cytokine production in vitro. RESULT: The regenerated epithelia of all C57BL/10
      (n=14) and B10.D2 (n=18) grafts were rejected swiftly in control mice, whereas
      66.6% of C57BL/10 grafts (8/12, P<0.001) and 62.8% of B10.D2 grafts (22/35,
      P<0.001) in the KLH immune group remained significantly clear for 8 weeks.
      Moreover, EGFP donor epithelial cells were detected from the healthy corneas of
      KLH-immunized mice. As for the in vitro assay, at 1 week after B10.D2 grafting,
      lymphocytes from KLH-immunized groups showed neither proliferation nor increased
      cytokine secretion. CONCLUSIONS: The Th2-biased immune system can support LT
      prolongation irrespective of donor disparity and can suppress corneal
      neovascularization. This prolongation is not due to induction of donor-specific
      regulatory cells, but is presumably at least associated with the suppression of
      allosensitization.

PMID- 14578394
TI  - Topographical thickness of the epithelium and total cornea after overnight wear
      of reverse-geometry rigid contact lenses for myopia reduction.
AB  - PURPOSE: To investigate topographical thickness changes of the epithelium and
      total cornea measured with optical coherence tomography (OCT) after overnight
      wear of rigid gas-permeable lenses. METHODS: Reverse geometry design CRT (Dk=100)
      rigid (test) lenses (Paragon Vision Sciences, Mesa, AZ) were randomly fitted on
      one eye of each of 20 neophyte subjects (mean age, 24.6 +/- 2.7 years) and the
      other eye was fitted with an alignment tricurve rigid lens of the same material
      (control). Epithelial and total corneal thickness was measured at intervals of 10
      degrees across a 10-mm zone of the horizontal meridian of the cornea, before and
      after overnight wear. Refractive error was measured with an autorefractor. These
      measurements were repeated 20 and 60 minutes and 3, 6, and 12 hours after lens
      removal. RESULTS: After one night of lens wear, myopia decreased in the test eye
      by 1.18 +/- 0.81 D, which was significantly different from baseline (P<0.001). No
      significant change was found in the control eye. Twelve hours after removal, two
      thirds of the myopic reduction was still present. Different topographical
      swelling patterns were induced by the two lens designs, with greatest swelling
      occurring in the center with the control lens and in the midperiphery with the
      test lenses (polynomial regression: P<0.005). Significantly greater central
      corneal swelling was found with the control lens than the test lens (6.9% +/-
      3.1% vs. 4.9% +/- 2.0%, respectively, P=0.006). The effect on epithelial
      thickness differed between lenses and depended on both position and time
      (F(48,912)=2.3; P=0.000). Immediately after removal of the test lens, the central
      epithelium was 5.1% +/- 4.5% thinner than baseline, and all other locations
      (P<0.005 post hoc tests) and the epithelium in the midperiphery showed
      significant thickening (1.9% on the temporal side and 2.4% on the nasal side,
      both P<0.006 compared with the baseline). There were no significant changes in
      epithelial thickness with the control lens during the study period (post hoc
      tests: P>0.05). CONCLUSIONS: The optical coherence tomograph is a sensitive
      instrument that can detect small changes in epithelial and corneal thickness
      across the entire cornea. Topographical thickness changes of the epithelium and
      total cornea induced by one night of reverse-geometry lens wear appear to be
      associated with the decrease of myopia.

PMID- 14578395
TI  - Factors influencing the decline in endothelial cell density after corneal
      allograft rejection.
AB  - PURPOSE: Corneal allograft rejection is one of the major causes of transplant
      failure. The purpose of the current study was to examine the decline in
      endothelial cell density (ECD) in patients experiencing allograft rejection, by
      comparing this decline with the normal evolution in patients who undergo
      penetrating keratoplasty (PKP) and to identify possible factors predictive of
      this endothelial cell loss after corneal allograft rejection. METHODS: In a case
      control study of 45 corneas that underwent corneal allograft rejection, specular
      microscopy photographs taken within the shortest time preceding the onset of
      rejection and after the resolution of the rejection were analyzed. RESULTS: The
      observed percentage loss of ECD in 21 (47%) corneas was not significantly greater
      than expected. A second group of 13 (29%) corneas showed a decline in ECD that
      was significantly greater than expected. Finally there were 11 corneas (24%) in
      which endothelial cells were no longer observable. The only two risk factors that
      reached statistical significance after multiple logistic regression analysis were
      a delay in diagnosis (a delay of >1 day yielded an odds ratio of 10.40; P=0.02)
      and a recipient age of more than 60 years (odds ratio, 6.95; P=0.04).
      CONCLUSIONS: Corneal allograft rejection does not necessarily cause a higher than
      expected endothelial cell loss; almost half of the patients in this study showed
      a decline in ECD that is comparable to the decline in patients who undergo PKP
      and have an uneventful follow-up. The most important variable influencing the
      extent of endothelial cells loss is a delay in diagnosis and treatment.

PMID- 14578396
TI  - The relationship between habitual patient-reported symptoms and clinical signs
      among patients with dry eye of varying severity.
AB  - PURPOSE: To investigate symptom profiles and clinical signs in subjects with dry
      eye and normal subjects in a cross-sectional multicenter study. METHODS: Subjects
      aged 35 to 65 were recruited according to dry eye diagnostic codes and telephone
      interview and completed the Dry Eye Questionnaire 2001, among others, and
      underwent dry eye clinical tests. RESULTS: Subjects (122) included 28 control
      subjects (C), 73 with non-Sjogren's keratoconjunctivitis sicca (non-SS KCS) and
      21 with Sjogren's syndrome (SS). Subjects with SS or non-SS KCS reported
      discomfort and dryness most frequently and that many symptoms worsened over the
      day and were quite bothersome. Groups were significantly different in corneal
      fluorescein staining, conjunctival lissamine green staining, Schirmer 1 tear
      test, and tear break-up time (TBUT; chi2 and Kruskal-Wallis, P<0.0001).
      Statistically significant, but moderate, correlations were found between the
      frequency and evening intensity of dryness and discomfort and TBUT, Schirmer's
      tear test, overall corneal fluorescein staining, and temporal lissamine green
      conjunctival staining (Spearman r=0.31-0.45, P<0.01). Symptoms were moderately to
      highly correlated with the clinician's global grading of severity and highly
      correlated to patient's self-assessment of severity (r=0.46-0.86, P<0.0001),
      whereas signs showed lower correlations (r=0.22-0.46, P<0.0001). CONCLUSIONS:
      Subjects with SS or non-SS KCS reported frequent and intense ocular surface
      symptoms in the evening, some of which correlated moderately with clinical test
      results. The global clinician grade of dry eye correlated more highly with
      patient symptoms than did clinical signs, suggesting that patient symptoms
      influence dry eye diagnosis and grading of dry eye more than clinical test
      results.

PMID- 14578397
TI  - Threshold vision in amblyopia: orientation and phase.
AB  - PURPOSE: The visual deficit in amblyopia involves both elevated contrast
      thresholds and distorted suprathreshold percepts at high spatial frequencies. It
      is currently unclear whether these two anomalies are part of the same neural
      disturbance or whether they reflect different neural dysfunction. METHODS: The
      quality of the spatial percepts in amblyopia was assessed at detection threshold.
      The ability of amblyopes to discriminate the orientation and local spatial phase
      of well-localized spatial stimuli was measured at the detection threshold.
      Measurements were made as a function of spatial frequency. RESULTS: Performance
      seemed normal for orientation discrimination, even at high spatial frequencies,
      but, in some cases, it was disturbed in phase discrimination. CONCLUSIONS: A
      different explanation and neural basis is needed to encompass both threshold and
      suprathreshold spatial deficits in amblyopia.

PMID- 14578398
TI  - Distribution of myocilin and extracellular matrix components in the corneoscleral
      meshwork of human eyes.
AB  - PURPOSE: To examine ultrastructurally the composition of major extracellular
      matrix (ECM) components and the distribution of myocilin in the trabecular
      lamellae of corneoscleral (CS) meshwork in normal human eyes. The codistribution
      of myocilin with ECM components was also investigated. METHODS: Postembedding
      immunoelectron microscopic studies were performed with antibodies against
      myocilin and other ECM components, including fibronectin, laminin, vitronectin,
      tenascin, elastin, fibrillin-1, microfibril-associated glycoprotein (MAGP)-1,
      decorin, versican, hyaluronic acid, and five types of collagen (I, III, IV, V,
      and VI). Double labeling of myocilin with other ECM components was performed with
      different sized gold particles. RESULTS: In the trabecular beams of CS meshwork,
      fibronectin, laminin, and collagen type IV were associated with basement
      membranes, whereas elastin was specifically localized to the core of elastic-like
      fibers. Several types of collagens, glycoproteins, proteoglycans, and hyaluronic
      acid were detected both in the collagen fibers and ground substances. Myocilin
      predominantly localized in the long-spacing collagens and sheath materials
      surrounding elastic-like fibers, codistributed with fibronectin, fibrillin-1,
      MAGP-1, decorin, and type VI collagen. CONCLUSIONS: This study illustrated the
      composition of ECM materials in the trabecular lamellae of CS meshwork. Myocilin
      was specifically localized to long-spacing collagens and the surrounding sheath
      of elastic-like fibers interacting with microfibril-associated elements where
      changes have been documented to occur in glaucomatous and aging eyes.

PMID- 14578399
TI  - Peripheral resolution for achromatic and SWS gratings in early to moderate
      glaucoma and the implications for selective ganglion cell density loss.
AB  - PURPOSE: To investigate whether there is significant selective reduction in short
      wavelength-sensitive (SWS) ganglion cell density in early to moderate glaucoma.
      METHODS: Peripheral achromatic resolution acuity (an indirect measure of the
      underlying midget ganglion cell density) and peripheral chromatic resolution
      acuity under conditions of blue cone isolation (an indirect measure of the
      underlying small bistratified ganglion cell density) were measured at 13 degrees
      eccentricity in four oblique meridians in 15 eyes (mean age, 64.6 +/- 9.6 years)
      with early to moderate glaucoma. The results from the subjects with glaucoma were
      compared with those in a group of 17 age-matched normal eyes (mean age, 62.5 +/-
      6.6 years). RESULTS: Mean achromatic resolution acuity across the four locations
      was significantly lower in the subjects with glaucoma than in the normal subjects
      (2.92 vs. 4.01 cyc/deg). Mean chromatic resolution acuity across the four
      locations was also significantly lower in the subjects with glaucoma than the
      normal subjects (0.78 vs. 0.99 cyc/deg). There was no selective loss of mean SWS
      acuity in the subjects with glaucoma. Individual location analysis revealed that
      the chromatic-achromatic resolution ratio was not significantly different in the
      subjects with glaucoma who had early glaucomatous damage when compared with the
      normal subjects. The chromatic-achromatic resolution ratio was lower than normal
      at certain locations in certain individuals with early glaucoma. CONCLUSIONS: The
      results indicate that there is no evidence of significant selective reduction in
      global SWS ganglion cell density in early to moderate glaucoma. However, there
      may be selective loss of SWS ganglion cell density at individual locations in
      individual eyes.

PMID- 14578400
TI  - Properties of perimetric threshold estimates from full threshold, ZEST, and SITA
      like strategies, as determined by computer simulation.
AB  - PURPOSE: To investigate the accuracy and precision of threshold estimates
      returned by two Bayesian perimetric strategies, staircase-QUEST or SQ (a Swedish
      interactive threshold algorithm [SITA]-like strategy) and ZEST (zippy estimation
      by sequential testing), and to compare these measures with those of the full
      threshold (FT) algorithm. METHODS: A computerized visual field simulation model
      was developed to compare the performance (accuracy, precision, and number of
      presentations) of the three algorithms. SQ implemented aspects of the SITA
      algorithm that are in the public domain. The simulation was tested by using
      standard automated perimetry (SAP) visual field data from 265 normal subjects and
      163 observers with glaucomatous visual field loss and by exploring the effect of
      response variability and response errors on algorithm performance. RESULTS: SQ
      was faster than FT or ZEST, with a comparable mean error when simulating field
      tests on patients. Point-wise analysis revealed similar error and standard
      deviation of error as a function of threshold for FT and SQ. If the initial
      estimate of threshold for either procedure was incorrect, the means and standard
      deviations of the error increased markedly. ZEST produced more accurate
      thresholds than did the other two strategies when the initial estimate was
      removed from the true threshold. CONCLUSIONS: When simulated patients made
      errors, the accuracy and precision of sensitivity estimates were poor when the
      initial estimate of threshold either overestimated or underestimated the true
      threshold. This was particularly so for FT and SQ. ZEST demonstrated more
      consistent error properties than the other two measures.

PMID- 14578401
TI  - Effect of heparin II domain of fibronectin on aqueous outflow in cultured
      anterior segments of human eyes.
AB  - PURPOSE: To determine whether an integrin/syndecan-binding domain of fibronectin,
      called the heparin II (Hep II) domain, affects outflow facility in the human eye.
      METHODS: Anterior segments of human eyes were placed in perfusion organ culture.
      One eye of each pair received the Hep II domain, and the fellow eye received DMEM
      or a heat-denatured Hep II domain. The Hep II domain was produced as a
      recombinant glutathione S-transferase (GST)-fusion protein. Microscopic changes
      were assessed. RESULTS: Outflow facility in anterior segments treated with Hep II
      domain increased by 93% compared with that in anterior segments treated with
      DMEM. In contrast, facility in anterior segments treated with the heat-denatured
      Hep II domain showed very little change. Outflow facility remained high during
      Hep II domain perfusion and returned to baseline after removal of the protein.
      Electron microscopy revealed disruptions in the endothelial lining of Schlemm's
      canal in anterior segments fixed during maximum effect and in anterior segments
      after facility had returned to baseline. Scattered disruptions of canal cells
      were noted in control anterior segments. Trabecular cells in other regions looked
      normal. Major changes in the extracellular matrix of the juxtacanalicular tissue
      were not observed. Repeated doses of the Hep II domain administered after
      facility returned to baseline increased facility in two of three anterior
      segments. CONCLUSIONS: The Hep II domain of fibronectin increases outflow
      facility in the human anterior segment. This suggests that fibronectin-mediated
      interactions may have a role in modulating aqueous hydrodynamics. Such
      interactions may represent avenues of novel therapeutic interventions for
      glaucoma.

PMID- 14578402
TI  - Tgf-beta inhibits activation and uveitogenicity of primary but not of fully
      polarized retinal antigen-specific memory-effector T cells.
AB  - PURPOSE: TGF-beta exerts suppressive effects on immunity, but its potential
      applications in therapy of ocular autoimmunity have not been widely explored. In
      the present study, the effects of TGF-beta on uveitogenic T cells were examined.
      METHODS: The effects of TGF-beta on newly primed cells from mice given a
      uveitogenic regimen of interphotoreceptor retinoid-binding protein (IRBP) were
      compared with the effects on fully polarized Th1 cells from a long-term
      uveitogenic T-cell line. The parameters measured were T-cell proliferation, IFN
      gamma production, induction of IL-12R expression, triggering of pathogenicity,
      and expression of costimulatory molecules on antigen-presenting cells (APCs)
      during in vitro exposure to antigen. RESULTS: TGF-beta suppressed B7.1 expression
      on APCs in cultures of lymph node cells from immunized mice. It also suppressed T
      cell proliferation, IFN-gamma production, IL-12 receptor accumulation, and the IL
      12-promoted acquisition of uveitogenic function. In contrast, the polarized Th1
      cells were either resistant to suppression or were enhanced by TGF-beta.
      CONCLUSIONS: The results suggest that TGF-beta suppresses acquisition of effector
      functions by autopathogenic T cells, in part by interfering with their response
      to IL-12 through downregulation of IL-12R expression and in part through
      inhibition of APC function. The data suggest that although TGF-beta may
      effectively inhibit activation and recruitment of new T cells into the effector
      pool, it may be less effective in suppressing the reactivation of already
      polarized memory T cells that are less dependent on IL-12 and costimulation.

PMID- 14578403
TI  - Ca2+-mobilization and cell contraction after muscarinic cholinergic stimulation
      of the chick embryo lens.
AB  - PURPOSE: In the embryonic lens, cells of the anterior epithelium proliferate,
      migrate through the equatorial zone, and elongate to form primary lens fibers at
      the posterior pole. During this stage of development, cholinesterase (ChE)
      activity has been described as in other embryonic tissues implicated in
      morphogenesis. The purpose of the study was to demonstrate in addition to ChE the
      presence of muscarinic acetylcholine receptors (mAChR) and choline
      acetyltransferase (ChAT) and to test whether the muscarinic cholinergic system is
      involved in the regulation of cellular movements. METHODS: In the chick embryo
      lens (Hamburger-Hamilton [HH] stage 21), the expression of mAChR and ChAT were
      demonstrated by immunohistochemistry. Isolated whole embryonic lenses were loaded
      with fura-2/AM, and changes of cytosolic calcium were measured after muscarinic
      stimulation. Size changes were assessed by morphometry with the use of time-lapse
      videos. RESULTS: mAChR was present in the equatorial zone of the lens and in the
      elongating primary lens fibers. Anti-ChAT immunoreactivity was restricted to the
      primary lens fibers. Addition of carbachol induced an intracellular Ca2+ peak
      followed by a plateau phase of extracellular Ca2+ influx. The plateau phase was
      reversed by addition of atropine. Concomitant with the calcium release, a
      contraction of the lens and an increase in opacity was observed. CONCLUSIONS: The
      localization of ChAT in the differentiating fibers of the lens indicates that
      acetylcholine is synthesized during differentiation and modulates morphogenesis
      and elongation of mAChR-positive progenitor cells in the equatorial zone. The
      carbachol-induced contraction indicates that the embryonic muscarinic system may
      be involved in the regulation of cellular movements.

PMID- 14578404
TI  - Water permeability of C-terminally truncated aquaporin 0 (AQP0 1-243) observed in
      the aging human lens.
AB  - PURPOSE: To first assess the distribution of posttranslationally truncated
      products of aquaporin 0 (AQP0) in dissected sections of a normal human lens and
      to determine the effect of backbone cleavage on the water permeability of AQP0.
      METHODS: A 27-year-old lens was concentrically dissected into six sections.
      Membrane protein was isolated from each section and cleaved with cyanogen
      bromide, and the peptides were separated and analyzed by reverse-phase (RP)-HPLC
      mass spectrometry (MS). The sites of posttranslational AQP0 C-terminal truncation
      were determined by mass spectrometry. Truncated forms of AQP0 were expressed in a
      Xenopus laevis oocyte system, and the effect of truncation on AQP0 water
      permeability was assessed in an oocyte osmotic swelling assay. RESULTS: The
      extent of truncation at many sites within the C terminus increased with fiber
      cell age, and the effects of truncations after residues 234, 238, and 243 on AQP0
      water permeability were examined. Truncation after residue 243 resulted in an
      approximate 15% decrease in permeability compared with the full-length protein,
      AQP0 1-263. However, rather than a direct effect on water transport, analysis of
      surface protein expression indicated that the decrease in permeability was a
      result of less efficient protein trafficking to the oocyte surface and that the
      permeabilities of full-length and 1-243 AQP0 were indistinguishable. Further, C
      terminal truncation of AQP0 to 1-234 and 1-238, completely impaired trafficking
      into the plasma membrane, precluding the measurement of permeability.
      CONCLUSIONS: These data provide evidence that loss of 20 amino acids from the C
      terminus may not directly affect the ability of AQP0 to transport water.

PMID- 14578405
TI  - Proteome analysis of lens epithelia, fibers, and the HLE B-3 cell line.
AB  - PURPOSE: The purpose of this study is to compare the protein composition of the B
      3 line of transformed human lens epithelial (HLE) cells to that of freshly
      dissected HLE cells. This provides baseline data on lens cell proteins from fresh
      lens cells and from the B-3 cell line, which is often used as a model system for
      the lens. METHODS: Human lens epithelial cells adherent to the lens capsule were
      dissected into central (undifferentiated) and peripheral (partially
      differentiated) populations. Fully differentiated human lens fiber cells were
      isolated from the outer cortical layers of the lens. HLE B-3 cells were analyzed
      at several passage levels. Extracts were prepared from each cell type and the
      proteins resolved by two-dimensional polyacrylamide gel electrophoresis (2-DE).
      Representative gel patterns were visually compared, spots excised, and trypsin
      digests prepared. The peptide compositions of the digests were analyzed using
      either liquid chromatography electrospray ionization tandem mass spectrometry or
      atmospheric pressure-matrix-assisted laser desorption ionization mass
      spectrometry, using a liquid chromatography classic ion trap (LCQ) mass
      spectrometer. RESULTS: Two-DE patterns were obtained for fresh and cultured cell
      types. Similar patterns were observed between central and peripheral HLE cells,
      both of which contained high levels of alphaA-, alphaB-, and betaB2-crystallins;
      alpha-enolase; and aldehyde dehydrogenase. HLE B-3 cultured cells were
      characterized by a marked loss of crystallins and a relatively higher level of
      noncrystallin proteins--most notably, high molecular weight, acidic proteins.
      Whereas subunit d of adenosine triphosphate (ATP) synthase, alphaB-crystallin,
      galectin, glyceraldehyde-3-phosphate dehydrogenase, alpha-enolase, actin,
      peptidylprolyl isomerase A, phosphatidylethanolamine-binding protein, and
      vimentin were present in both fresh and cultured lens epithelium, only the high
      abundance of alpha-enolase, galectin-1, and vimentin suggested that B-3 cells
      were lens derived. CONCLUSIONS: Freshly dissected noncultured HLE cells from both
      central and peripheral regions contain a high concentration of crystallins that
      mask the detection of less abundant proteins by 2-DE. Transformation and culture
      of HLE cells causes a loss of these crystallins and an increase in the relative
      concentration of other proteins. However, most of these noncrystallin proteins
      were different from those observed in noncultured HLE cells. These results
      suggest that transformation markedly alters the protein expression pattern in
      immortalized HLE cells and that caution should be exercised when using them to
      study properties of HLE cells in vivo.

PMID- 14578406
TI  - Pharmacological characterization of a serotonin receptor (5-HT7) stimulating cAMP
      production in human corneal epithelial cells.
AB  - PURPOSE: To study the mRNA and pharmacology of a serotonin (5-HT) receptor
      positively coupled to adenylyl cyclase in normal, primary (P-CEPI), and
      immortalized human corneal epithelial cells (CEPI-17-CL4), by using numerous 5-HT
      agonists and antagonists. To determine and compare cloned human 5-HT7 receptor
      binding affinities of compounds with their functional potency data. METHODS: RT
      PCR was used to detect the presence of an mRNA for the human 5-HT7 receptor in
      CEPI-17-CL4 cells. Receptor-mediated production of cAMP in cultured cells was
      measured using an enzyme immunoassay. Compound binding affinities were determined
      using [3H]-lysergic acid diethylamide ([3H]-LSD) binding to cell membranes of
      human embryonic kidney (HEK-293) cells expressing the cloned human 5-HT7
      receptor. RESULTS: RT-PCR revealed the presence of a 5-HT7 receptor mRNA in CEPI
      17-CL4 cells. Normal P-CEPI cells generated cAMP in response to 5-HT (-log EC50;
      pEC50=7.6), 5-carboxamidotryptamine (5-CT; pEC50=7.8), 5-methoxy-tryptamine
      (pEC50=7.0) and 5-methoxy-dimethyl-tryptamine (pEC50=5.7). In CEPI-17-CL4 cells,
      serotonergic agonists also stimulated cAMP production with different potencies
      (pEC50): 5-CT (7.4)>5-HT (6.5)> or =5-methoxy-tryptamine (6.1)>5-methoxy-dimethyl
      tryptamine (5.4)> or =8-OH-DPAT (<5.0)=alpha-methyl-5-HT (<5.0). Various 5-HT
      receptor antagonists inhibited cAMP production induced by 5-CT in CEPI-17-CL4
      cells with different potencies (pKi): methiothepin (8.5)>mesulergine
      (8.1)=metergoline (8.0)>spiperone (7.4)> or =clozapine (7.2)=SB-258719
      (7.2)>mianserin (6.9)>ketanserin (6.3). Antagonist pKi values in P-CEPI cells
      were methiothepin (8.7), spiperone (7.4) and SB-258719 (6.6). The rank order of
      affinity for displacement of [3H]-LSD from the cloned human 5-HT7 receptor was:
      methiothepin>ritanserin>mesulergine=clozapine> or =metergoline=5-HT>SB-258719> or
      =spiperone>mianserin> or =ketanserin. The functional agonist and antagonist
      potency data obtained from CEPI-17-CL4 cells correlated well with cloned human 5
      HT7 receptor binding affinity data (r=0.69), with P-CEPI cell functional data
      (r=0.85), and with functional potency data in the literature for the cloned human
      5-HT7 receptor (r=0.88). CONCLUSIONS: These collective data support the presence
      of a pharmacologically defined, adenylyl cyclase-coupled 5-HT7 receptor in the
      CEPI-17-CL4 cells that may have relevance to physiological and/or pathologic
      functions of 5-HT7 receptors in the human cornea.

PMID- 14578407
TI  - Scleral plug of biodegradable polymers containing tacrolimus (FK506) for
      experimental uveitis.
AB  - PURPOSE: To evaluate the efficacy of a biodegradable polymeric scleral plug
      containing the immunosuppressive agent, FK506, in a rabbit model for experimental
      uveitis. METHODS: The scleral plugs were prepared by dissolving poly(DL-lactide
      co-glycolide; PLGA) and FK506 (weight, 8.5 mg; length, 5 mm; 1% FK506). The
      release of FK506 was evaluated in vitro by spectrophotometry on days 1, 3, 7, 14,
      21, and 35. In vivo, FK506 concentrations of the vitreous were measured by high
      performance liquid chromatography 2 and 4 weeks after intravitreous plug
      implantation in pigmented rabbits. Sixteen pigmented rabbits were immunized twice
      subcutaneously with 10 mg of Mycobacterium tuberculosis H37Ra antigen. Twelve
      days later, the right eyes of all rabbits were challenged with an intravitreal
      injection of 50 micro g of antigen. After the first challenge, the 16 eyes of 16
      pigmented rabbits were divided into two groups. Scleral plugs were implanted into
      the vitreous of the right eye of eight rabbits. Eight control rabbits received a
      sham device. The aqueous protein concentrations and cell counts were determined
      on postchallenge days 7, 14, and 28. To simulated chronic inflammation, the eyes
      were rechallenged with intravitreal antigen on day 14 and were observed for 1
      month. Inflammation of the anterior chamber and the vitreous were graded
      clinically by two masked observers. Retinal function was evaluated by
      electroretinography (ERG) and histologic examination. RESULTS: Clinical scores
      (anterior chamber cells, flare, and vitreous opacity) showed that treated eyes
      had significantly less inflammation than untreated eyes (P<0.001). Quantitative
      analysis of inflammatory cells (P<0.001) and protein concentrations (P<0.0001) in
      the anterior chamber showed significant decreases in treated eyes.
      Histopathologic examination showed marked inflammation and tissue disorganization
      in the untreated eyes. No retinal toxicity was detected, histopathologically and
      electroretinographically. After antigen rechallenge, inflammation in experimental
      eyes was still less than in control eyes. CONCLUSIONS: Intravitreal sustained
      release of FK506 from a biodegradable polymeric scleral plug was highly effective
      in suppressing the inflammation of experimental uveitis in a rabbit model for at
      least 6 weeks. This device may be useful in the management of patients with
      severe chronic uveitis.

PMID- 14578409
TI  - Effects of isometric exercise on subfoveal choroidal blood flow in smokers and
      nonsmokers.
AB  - PURPOSE: Little is known about potential effects of smoking on ocular blood flow
      regulation. In the present study, the hypothesis was that choroidal blood flow
      (CBF) changes during an increase in ocular perfusion pressure induced by
      isometric exercise are altered in chronic smokers. METHODS: The study was
      performed in 24 (12 smokers and 12 nonsmokers) healthy male volunteers in an
      observer-masked, two-cohort study design. The difference in CBF regulation
      between smokers and nonsmokers was tested during isometric exercise over a period
      of 6 minutes. CBF was assessed with laser Doppler flowery (LDF), and ocular
      perfusion pressure (OPP) was calculated from mean arterial pressure (MAP) and
      intraocular pressure (IOP). RESULTS: Six minutes of isometric exercise induced a
      significant increase in MAP, pulse rate (PR), OPP, and CBF in smokers and
      nonsmokers (each P<0.001). The increase in CBF was significantly higher in the
      smoking group (P<0.001) than in the healthy control group, whereas a comparable
      increase in MAP (P=0.18), PR (P=0.18), and OPP (P=0.43) occurred in smokers and
      nonsmokers. IOP remained unchanged during isometric exercise in both groups.
      Moreover, in smokers, CBF started to increase at OPPs more than 49% above
      baseline, whereas CBF in nonsmokers remained stable until an increase in OPP of
      74% over baseline. This difference between the two groups was significant
      (P<0.001). CONCLUSIONS: These data indicate abnormal CBF regulation in chronic
      smokers compared with age-matched nonsmoking subjects during isometric exercise.
      The pathways responsible for this abnormal blood flow response remain to be
      elucidated.

PMID- 14578408
TI  - Effect of ibopamine on aqueous humor production in normotensive humans.
AB  - PURPOSE: Ibopamine is a prodrug of epinine (deoxyepinephrine) that exhibits
      activity at dopaminergic and adrenergic receptors. Topical ocular application has
      been shown to cause mydriasis without cycloplegia and to increase the rate of
      aqueous humor flow in normotensive human eyes. Mydriasis can interfere with the
      measurement of aqueous flow. In this study ibopamine's effect on aqueous humor
      production was measured while making allowance for the potential artifact caused
      by its mydriatic effect. METHODS: The effects of topical ibopamine on pupillary
      diameter, aqueous humor flow measured by fluorophotometry, and intraocular
      pressure were studied in 24 healthy, blue-eyed humans. Ibopamine was administered
      with and without the alpha-adrenergic antagonist dapiprazole, and its effects
      were compared with those of tropicamide, with and without dapiprazole in a double
      masked, randomized, crossover design. RESULTS: Ibopamine dilated the pupil from a
      diameter of 3.7 +/- 0.64 (mean +/- SD, n=24) to 7.7 +/- 0.70 mm. Ibopamine,
      during its peak mydriasis, was associated with a very large increase in the rate
      of clearance of topically applied fluorescein from the cornea and anterior
      chamber, an effect that was not associated with tropicamide during its peak
      mydriasis. The mydriatic effect of ibopamine was completely blocked by
      dapiprazole, and the increase in fluorescein clearance was partially blocked.
      When mydriasis was blocked, ibopamine increased fluorescein clearance by 13%
      (P<0.0001), which was interpreted as an increased rate of aqueous humor
      production. Compared with placebo and with the tropicamide control, ibopamine
      decreased intraocular pressure, despite its stimulation of aqueous humor flow.
      CONCLUSIONS: Ibopamine is in a specific class of drug, along with pilocarpine,
      epinephrine, and bimatoprost that in humans increases the rate of aqueous humor
      flow as measured by fluorophotometry. This effect is partly responsible for its
      ability to increase intraocular pressure in persons suspected to have abnormally
      low aqueous humor outflow facility. The transient apparent doubling of aqueous
      humor flow, measured by fluorescein clearance after administration of ibopamine
      is an artifact of increased fluorescein clearance through the dilated pupil while
      accommodation is active.

PMID- 14578410
TI  - Effects of lomerizine, a calcium channel antagonist, on retinal and optic nerve
      head circulation in rabbits and humans.
AB  - PURPOSE: To investigate the effects of lomerizine, a Ca2+ antagonist, on the
      ocular tissue circulation in rabbits and on the circulation in the optic nerve
      head (ONH) and choroid in healthy volunteers. METHODS: Lomerizine (0.1 [n=10] or
      0.3 [n=11] mg/kg) or vehicle solution (n=11) was injected intravenously in
      urethane-anesthetized rabbits, and blood flow in the retina, choroid, and iris
      ciliary body was measured by the microsphere method and that in the ONH by the H2
      gas-clearance method (0.1 [n=6] or 0.3 [n=9] mg/kg or vehicle, n=6). Oral 5 mg
      lomerizine or placebo was administered to volunteers (n=8) in a crossover study,
      and in areas of the fovea and ONH, the normalized blur (NB), a quantitative index
      of blood velocity, was measured, together with blood pressure, heart rate, and
      intraocular pressure (IOP), before and 1.5, 3, 6, and 9 hours after
      administration. RESULTS: Blood flow in the rabbit retina increased significantly
      in the lomerizine-treated group, but blood flow changed little in the choroid or
      iris-ciliary body. Blood flow in the rabbit ONH also showed a significant
      increase in the lomerizine-treated group. In human studies, the NB obtained from
      the ONH during the experimental period showed a small but significant increase in
      the lomerizine-treated group compared with the placebo-treated group, but no
      significant intergroup difference was detected in the NB obtained from the fovea
      or in blood pressure, heart rate, or IOP. CONCLUSIONS: Lomerizine increases blood
      velocity, and probably blood flow, in the ONH and retina in rabbits, and it also
      increases blood velocity in the ONH in healthy humans, without significantly
      altering blood pressure or heart rate.

PMID- 14578411
TI  - Effects of sildenafil on retinal blood flow and flicker-induced retinal
      vasodilatation in healthy subjects.
AB  - PURPOSE: Sildenafil is a specific inhibitor of phosphodiesterase V, which is
      widely used for the treatment of erectile dysfunction. Sildenafil has been shown
      to induce vasodilation in several vascular beds by inhibiting the cGMP breakdown.
      The present study was conducted to investigate whether sildenafil increases blood
      flow in the human retina. METHODS: In a randomized, double-masked, placebo
      controlled, two-way crossover study in 12 healthy male volunteers the effects of
      a single dose of 100 mg sildenafil were studied. Subjects received sildenafil or
      placebo on two different study days. After administration, retinal hemodynamic
      parameters were measured every 20 minutes. Retinal vessel diameters and retinal
      blood velocity were assessed with the retinal vessel analyzer and bidirectional
      laser Doppler flowmetry, respectively. In addition, the response of retinal
      vessel diameters to stimulation with diffuse flicker light was studied. Blood
      pressure and intraocular pressure were measured with noninvasive techniques.
      RESULTS: Sildenafil had no effect on mean arterial pressure, pulse rate,
      intraocular pressure, retinal blood velocity, or retinal arterial diameter.
      However, a significant increase in retinal venous diameters (4.7% +/- 3.2%;
      P=0.0028 versus placebo) and retinal blood flow 15.7% +/- 18.0%; P=0.029 versus
      placebo) was observed. Sildenafil had no effect on flicker-induced vasodilation
      in retinal arteries or veins. CONCLUSIONS: The data indicate that sildenafil
      increases retinal venous diameters and retinal blood flow in healthy subjects. By
      contrast, it does not affect intraocular pressure and flicker-induced retinal
      vasodilation. Further studies are needed to elucidate whether this drug may be
      therapeutically used in retinal ischemic disease.

PMID- 14578412
TI  - Distribution of rat organic anion transporting polypeptide-E (oatp-E) in the rat
      eye.
AB  - PURPOSE: To examine the protein and mRNA expression levels of the recently cloned
      rat multifunctional Na+-independent organic anion transporting polypeptide (rat
      oatp-E), which is involved in the transport of thyroid hormone in the rat, the
      distribution and function of this transporter were investigated in the retina.
      METHODS: Real-time quantitative reverse transcription-polymerase chain reaction
      (RT-PCR) was performed with gene-specific primers for oatp-E in rat ocular
      tissues. Western blot analysis was performed by raising a specific antibody
      against oatp-E in rat ocular tissues. Immunohistochemistry was performed with a
      specific antibody for oatp-E in paraffin sections of rat eyes. The expression of
      oatp-E in isolated and cultured rat retinal pigment epithelial (RPE) cells was
      confirmed by RT-PCR, Western blot analysis, and immunohistochemistry. In
      addition, oatp-E function was analyzed in cultured rat RPE cells by measuring the
      uptake of triiodothyronine (T3), which is a known substrate for oatp-E. RESULTS:
      Using real-time quantitative RT-PCR, oatp-E mRNA was detected, in order of
      highest to lowest concentration, in the rat retina, cornea, and ciliary body
      iris. A single band for oatp-E was observed by Western blot analysis in the rat
      brain, retina, cornea, and ciliary body-iris. oatp-E immunostaining was
      predominantly expressed in the corneal epithelium, in the pigmented and
      nonpigmented epithelium of the ciliary body, and in the iris of the rat eye. In
      the rat retina, intense immunostaining was detected in the RPE, inner and outer
      nuclear layers, ganglion cell layer, and nerve fiber layer. In addition, oatp-E
      immunoreactivity in cultured rat RPE cells was expressed in the cell membrane and
      cytoplasm of RPE cells, a finding that was also confirmed by RT-PCR and Western
      blot analysis. RPE cells, which were shown to express high levels of oatp-E,
      transported T3 in a saturable and dose-dependent manner. Moreover, this uptake
      was significantly inhibited by sulfobromophthalein (BSP), an inhibitor of oatp,
      suggesting that oatp-E may in part contribute to this uptake. CONCLUSIONS:
      Results from the present study revealed that rat oatp-E is localized mainly to
      the corneal epithelium, ciliary body, iris, and retina. Furthermore, the findings
      appear to suggest that transport of T3 in the RPE may have a functional role for
      organic anion (i.e., thyroid hormone) transport in the rat eye.

PMID- 14578413
TI  - Endothelin-1 synthesis and secretion in human retinal pigment epithelial cells
      (ARPE-19): differential regulation by cholinergics and TNF-alpha.
AB  - PURPOSE: Endothelin (ET)-1 can produce nerve damage analogous to that in optic
      neuropathies such as glaucoma. The precise source of endothelin in the posterior
      segment of the eye remains unclear. The present study was conducted to determine
      whether the retinal pigment epithelium (RPE), which helps maintain the outer
      blood-retinal barrier, is a local source for ET-1 and whether the amount of ET-1
      secreted by the RPE is be differentially regulated by cholinergics and the
      cytokine TNF-alpha. METHODS: Human retinal pigment epithelial cells (ARPE-19)
      were cultured either to a mature state (mRPE) for 4 weeks, with well-defined
      tight junctions, or to a young state (yRPE) for 4 days, with incompletely formed
      tight junctions. ET-1-like immunoreactivity was determined by
      immunocytochemistry, and secreted ET-1 was quantified by radioimmunoassay in both
      cell types. Cells were stimulated with the cholinergic agonist carbachol or with
      the cytokine TNF-alpha for specific periods. The expression of muscarinic
      receptor subtypes M1 and M3 and the peripheral membrane protein ZO-1 were
      analyzed by immunoblot and immunocytochemistry, respectively. Expression of
      preproendothelin-1 (ppET-1) mRNA after application of different stimuli at
      specific time points was determined by real-time RT-PCR. Carbachol-mediated
      elevation in intracellular calcium ([Ca2+]i) was also measured in the presence or
      absence of a selective muscarinic receptor antagonist. RESULTS: Constitutive
      synthesis and secretion of ET-1 was greater in mRPE than in yRPE cells. TNF-alpha
      caused a significant increase in ppET-1 mRNA levels and ET-1 secretion in both
      phenotypes. The disruption and subsequent breakdown of the tight junction barrier
      was evident in either phenotype after treatments with TNF-alpha. There was a
      concentration-dependent increase in [Ca2+]i in both y- and mRPE cells in response
      to CCh. CCh at 1 microM significantly increased ET-1 secretion, a response
      observed in yRPE but not in mRPE cells. This effect may be mediated primarily by
      the M3 receptor subtype and is phospholipase C (PLC) dependent. CONCLUSIONS:
      Regulation of ET-1 release in ARPE-19 cells was differentially regulated by TNF
      alpha and CCh and was dependent on the age of the culture. RPE may be a source
      for ET-1 in the retina, and its increased release may become more important
      during breakdown of the blood-retinal barrier, as seen after TNF-alpha treatment.

PMID- 14578414
TI  - Pharmacokinetic and toxicity study of an intraocular cyclosporine DDS in the
      anterior segment of rabbit eyes.
AB  - PURPOSE: To establish the safety and pharmacokinetic efficacy of an Oculex Drug
      Delivery System (DDS; Oculex Pharmaceuticals, Inc., Sunnyvale, CA) containing
      cyclosporin A (CsA) in the anterior segment of the rabbit eye. METHODS: The
      Oculex DDS is an intraocular, sustained-release, drug delivery system comprising
      a biodegradable lactic acid-glycolic acid copolymer. A controlled prospective
      study was performed that involved implanting a DDS containing 0.5 mg of CsA into
      the anterior chamber (AC) of the right eyes of 16 New Zealand White rabbits. A
      placebo DDS was implanted into the left eyes of these same rabbits as the
      control. Slit lamp examinations and AC taps were performed serially, and the
      rabbits were killed and the globes removed at 2, 4, 8, and 12 weeks for histology
      and determination of CsA drug levels. Analysis of CsA levels was performed with
      high-performance liquid chromatography-mass spectrometry. RESULTS: High
      concentrations of CsA were detectable in all layers of the cornea (epithelium,
      corneal stroma and endothelium) throughout the 3-month period. Low CsA levels
      were detected in the aqueous, whereas no CsA was detectable in the blood. There
      were no adverse reactions observed. CONCLUSIONS: The Oculex DDS CsA device is
      effective in delivering long-term levels of CsA to corneal tissues, without
      adverse effects. Further studies in an animal model of corneal transplant
      rejection should be performed to determine the potential of this device in the
      prophylaxis and treatment of corneal transplant rejection in humans.

PMID- 14578415
TI  - The cavernous body of the human efferent tear ducts contributes to regulation of
      tear outflow.
AB  - PURPOSE: To test the hypothesis that the surrounding vascular plexus of the
      lacrimal sac and the nasolacrimal duct contributes to the regulation of tear
      outflow. METHODS: Experiments in 30 probands aged between 15 and 37 years were
      performed in both nasolacrimal systems of each subject by observing with an
      endoscope the transit time of an applied tear drop containing fluorescein dye
      until its entry into the inferior meatus of the nose. Four different experiments
      were performed to determine the median transit time under normal conditions and
      the influence on transit time of a decongestant drug, a foreign body on the
      ocular surface, and a decongestant drug applied together with a foreign body on
      the ocular surface. Comparisons were made between the right and left nasolacrimal
      system, in males and females, eyeglass wearers and non-eyeglass wearers, and the
      different experiments and the results statistically analyzed. RESULTS: The tear
      transit time was independent of side (right or left), gender, or eyeglass wear.
      It showed great individual variability. Application of a decongestant drug or
      placement of a foreign body on the ocular surface both prolonged the dye transit
      time significantly. Application of a decongestant drug simultaneously with
      placement of a foreign body shortened the dye transit time significantly compared
      with the effect of the decongestant drug alone but revealed no significant
      difference compared with application of a foreign body alone. CONCLUSIONS: The
      cavernous body of the lacrimal sac and nasolacrimal duct plays an important role
      in the physiology of tear outflow regulation. It is subject to autonomic control
      and is integrated into a complex neuronal reflex feedback mechanism starting with
      the dense innervation of the cornea. Moreover, its function can be
      pharmacologically influenced.

PMID- 14578416
TI  - The role of adult bone marrow-derived stem cells in choroidal neovascularization.
AB  - PURPOSE: Age-related macular degeneration (ARMD) is the primary cause of
      blindness in people aged of 50 years or more. The wet form leads to severe loss
      of central vision. Recent evidence supports that adult hematopoietic stem cells
      (HSCs) contribute to preretinal neovascularization. In the current study, it was
      determined whether HSCs, by producing both blood and blood vessels, provide
      functional hemangioblast activity during choroidal neovascularization (CNV) in
      mice. METHODS: Gfp chimeric mice were developed by bone marrow ablation of
      C57BL/6J mice and reconstitution with donor tissue from gfp(+/+) transgenic mice.
      Gfp chimeric mice underwent laser rupture of Bruch's membrane and were killed and
      eyes enucleated at 1, 2, 3, and 4 weeks after laser injury. CNV was examined by
      confocal microscopy of retinal flatmounts. Because endothelial progenitor cells
      (EPCs) derive from HSCs, immunocytochemistry was used to quantify relative the
      EPC contribution to CNV. RESULTS: Laser injury alone was sufficient to induce
      stem cell recruitment and subsequent CNV. Gfp+ cells formed part of the
      functional vasculature in the choroid as early as 1 week after injury and were
      present for the duration of the study. The relative EPC contribution to CNV
      remained fairly constant throughout the study and constituted almost 50% of the
      total vasculature. CONCLUSIONS: Adult stem cells are recruited to the choroid in
      a model of CNV, where they contribute to forming aberrant new vessels. This
      observation suggests that targeting stem cell recruitment to the eye may offer a
      novel therapeutic strategy for ARMD.

PMID- 14578417
TI  - Bone marrow-derived progenitor cells contribute to experimental choroidal
      neovascularization.
AB  - PURPOSE: The pathogenesis of choroidal neovascularization (CNV) is postulated to
      be driven by angiogenesis, a process in which the cellular components of the new
      vessel complex are derived from cells resident within an adjacent preexisting
      capillary. Recently, an alternative paradigm, termed postnatal vasculogenesis,
      has been shown to contribute to some forms of neovascularization. In
      vasculogenesis, the cellular components of the new vessel complex are derived
      from circulating vascular progenitors from bone marrow. In the current study,
      transplantation of green fluorescent protein (GFP)-labeled bone marrow and laser
      induced CNV were combined to examine the contribution of vasculogenesis to the
      formation of CNV. METHODS: Ten adult C57BL/6 female mice were used as recipients
      for bone marrow transplantation. Bone marrow was obtained from three C57BL/6
      female mice transgenic for the beta-actin promoter GFP. One month after bone
      marrow transplantation, CNV was induced in recipient mice by making four separate
      burns in the choroid of each eye with a red diode laser. Four weeks after CNV was
      induced, eyes of recipient mice were processed for immunohistochemistry to detect
      GFP and markers for vascular smooth muscle cells (alpha-smooth muscle actin,
      desmin, and NG2 chondroitin sulfate proteoglycan), endothelial cells (CD31, BS-1
      lectin), or macrophages (F4/80). RESULTS: GFP-labeled cells represented 17% of
      the total cell population in the lesion. Many of the GFP-labeled cells were
      immunoreactive for alpha-smooth muscle actin (39%), desmin, NG2, CD31 (41%), BS-1
      lectin, or F4/80. GFP-labeled cells were morphologically indistinguishable from
      cells normally present in CNV lesions. CONCLUSIONS: This study is the first to
      demonstrate that bone marrow-derived progenitor cells are a source of endothelial
      and smooth musclelike cells in CNV.

PMID- 14578418
TI  - Multifocal electroretinograms in X-linked retinoschisis.
AB  - PURPOSE: To study local retinal cone function in patients with X-linked
      retinoschisis (XLRS) by multifocal ERGs (mfERGs). METHODS: mfERGs were recorded
      from seven eyes of seven patients with XLRS (mean age +/- SD, 22.1 +/- 3.2 years;
      range, 18 to 25 years). Five eyes had microcystic changes in the macula and two
      eyes had nonspecific macular degeneration. Two eyes had peripheral retinoschisis,
      and some of the stimuli fell on this area. The stimulus array consisted of 103
      hexagons and the total recording time was set at approximately 4 minutes. The
      amplitudes and implicit times of both focal and summed responses for the first-
      and second-order kernels were analyzed. RESULTS: The amplitudes of the first
      order kernel were markedly reduced in the central retina in all eyes. A large
      variation was observed in the amplitudes outside the fovea. The amplitudes of the
      focal cone ERGs at the peripheral retinoschisis did not differ from those
      recorded from adjacent retinal loci without the retinoschisis. The implicit times
      of the first-order kernel were significantly delayed, and the amplitudes of the
      second-order kernels were more affected than the first-order kernels across the
      whole field in all XLRS eyes. CONCLUSIONS: The cone-mediated retinal responses
      were more impaired in the central than peripheral retina in eyes with XLRS.
      Delayed implicit times of the first-order kernel and reduced second-order kernel
      across the whole testing field in all XLRS eyes suggest that there is widespread
      cone-system dysfunction in XLRS.

PMID- 14578419
TI  - Upregulation of P-selectin and intercellular adhesion molecule-1 after retinal
      ischemia-reperfusion injury.
AB  - PURPOSE: Vascular endothelial cells and leukocytes express several inflammatory
      adhesion receptors, such as selectins and cell adhesion molecules, after retinal
      ischemia. They mediate the transmigration process of leukocytes. For further
      understanding of the role of leukocytes after retinal ischemia-reperfusion
      injury, the responses of the leukocyte-endothelial cell adhesion molecules P
      selectin and intercellular adhesion molecule (ICAM)-1 during retinal ischemia and
      reperfusion were examined. METHODS: Male pigmented rats were subjected to retinal
      ischemia by a 1-hour ligation of the optic nerve followed by reperfusion. Gene
      and protein expression of P-selectin and ICAM-1 were studied at 0.5, 1, 6, 12,
      and 24 hours after the onset of reperfusion with semiquantitative polymerase
      chain reaction and Western blot analysis. Immunohistochemical methods were used
      to detect specific lesions expressing ICAM-1. RESULTS: Significant upregulation
      of P-selectin and ICAM-1 mRNA (at 6, 12, and 24 hours of reperfusion) were
      observed, with the expression peaks of both P-selectin and ICAM-1 mRNA occurring
      at 12 hours after reperfusion. P-selectin protein gradually increased and reached
      a maximum 6 hours after reperfusion, whereas ICAM-1 protein increased until 24
      hours after reperfusion. Immunostaining with ICAM-1 antibodies was positive in
      endothelial cells after ischemia-reperfusion injury. CONCLUSIONS: Retinal
      ischemia-reperfusion stimulates P-selectin and ICAM-1 expression. Endothelial
      ICAM-1 expression in retinal vessels was observed. Upregulation of P-selectin and
      ICAM-1, which contribute to leukocyte rolling and adhesion, were observed after
      retinal ischemia.

PMID- 14578420
TI  - Neuronal integration in an abutting-retinas culture system.
AB  - PURPOSE: Limited integration is consistently observed between subretinal
      transplants and host retinas. In the current study, an in vitro model system for
      studying connections forming between two abutting retinas was developed. METHODS:
      Neuroretinas were dissected from normal wild-type (WT) mice and green fluorescent
      protein (GFP) transgenic mice (obtained at postnatal days [P]0, P5, or P60), as
      well as from adult rd mice. Pieces from two different retinas (WT-WT, GFP-WT, GFP
      rd) were placed side-by-side (contacting each other at the margins) or
      overlapping each other in organ cultures for 7 or 12 days. The abutting retinal
      pieces derived from animals of the same age (P5-P5; P60-P60) or of different ages
      (P0-P60; P5-P60). Retinal cells and fibers were visualized in wholemount
      preparations and in cross sections by immunocytochemistry using antibodies
      against neurofilament (NF+), neuronal nitric oxide synthase (NOS+), and protein
      kinase C (PKC+) and by GFP fluorescence (GFP+). RESULTS: In side-by-side pairs
      (WT-WT, GFP-WT), numerous horizontal cell fibers (NF+) and amacrine cell fibers
      (NOS+) crossed the interface between the two pieces, forming continuous plexiform
      layers. In overlapping pairs, NF+, NOS+, and PKC+ fibers displayed parallel
      plexiform layers, and no crossover of fibers was observed in any of the pair
      combinations examined (WT-WT, GFP-WT, GFP-rd). Some integration was seen only in
      small areas where the structure of both retinal pieces was disrupted at the
      interface. CONCLUSIONS: The results demonstrate the ability of neurites to extend
      between abutting retinas and to make appropriate target choices when they are
      placed side-by-side. However, this ability is limited when they overlap each
      other, similar to that observed in subretinal transplantation.

PMID- 14578421
TI  - Role of nitric oxide in regulation of retinal blood flow during hypercapnia in
      cats.
AB  - PURPOSE: To investigate whether nitric oxide (NO) contributes to the regulation
      of retinal circulation during hypercapnia in cats. METHODS: NG-nitro-L-arginine
      methylester (L-NAME; n=8), a NOS inhibitor; NG-nitro-D-arginine-methylester (D
      NAME; n=6), the inactive isomer; or phosphate-buffered saline (PBS; n=8) was
      injected intravitreously into the cat's eye. A selective neuronal nitric oxide
      synthase (nNOS) inhibitor, 7-nitroindazole (7-NI; n=6), was injected
      intraperitoneally. Hypercapnia was induced for 10 minutes by inhalation of 5%
      carbon dioxide with 21% oxygen and 74% nitrogen. The vessel diameter and blood
      velocity were measured simultaneously in large retinal arterioles in cats by
      laser Doppler velocimetry and the retinal blood flow (RBF) calculated. Retinal
      vascular resistance (RVR) was also estimated. RESULTS: In the PBS group, the
      vessel diameter (9.5% +/- 2.7%, P<0.05), blood velocity (15.6% +/- 4.4%, P<0.05),
      and RBF (37.2% +/- 3.7%, P<0.05) increased, and the RVR decreased (-26.0% +/-
      2.7%, P<0.05) during hypercapnia. In the L-NAME group, those changes were greatly
      suppressed in response to hypercapnia. D-NAME was inactive with regard to RBF
      during hypercapnia. The RBF responses to hypercapnia after the 7-NI injection
      were significantly attenuated compared with those before 7-NI injection (P<0.05).
      CONCLUSIONS: These results indicate that NO contributes to the increase in RBF
      during hypercapnia. Furthermore, the NO synthesized by the action of nNOS may
      participate in regulation of RBF during hypercapnia.

PMID- 14578422
TI  - Multifocal electroretinographic features of central retinal vein occlusion.
AB  - PURPOSE: To determine the features of wide-field multifocal electroretinography
      (WF-mfERG) recorded in patients with central retinal vein occlusion (CRVO) and to
      compare WF-mfERG responses of the affected and fellow eyes. In addition, WF-mfERG
      responses were also compared by using standard electroretinography (ERG).
      METHODS: WF-mfERG and ERG responses were recorded from both eyes of 56 patients
      with CRVO. The WF-mfERG responses, obtained using a custom-built system were
      grouped into central and peripheral rings. The P1 amplitudes, and P1 and N1
      implicit times were grouped and averaged within both rings. Nonparametric
      statistical analysis was used to compare the ERG results from the affected and
      fellow eyes. The results were also compared with normative data (5% to 95%
      confidence limits). RESULTS: CRVO markedly affected all the parameters of the WF
      mfERG. In the affected eyes, 98% of the central and 91% of the peripheral P1
      implicit times fell outside the normal range, as opposed to 35% of the 30-Hz
      flicker implicit times. The WF-mfERG responses obtained from eyes with CRVO were
      significantly different (P<0.01) from those derived from the fellow eye. The
      central and peripheral P1 implicit times were also abnormal in 59.2% and 46.9% of
      the fellow eyes, respectively. CONCLUSIONS: WF-mfERG is more susceptible than the
      standard ERG to changes in the nonlinear dynamics of the eye due to the multiple
      frequencies of stimulation used to record WF-mfERG responses. WF-mfERG could be a
      sensitive indicator of the underlying disease affecting the retina in eyes with
      CRVO and may have a role in the clinical setting.

PMID- 14578423
TI  - Structural and hemodynamic analysis of the mouse retinal microcirculation.
AB  - PURPOSE: In the holangiotic retina, little is known about the connections between
      and the circulation within microvessel layers. The goal of the present study was
      to explore the three-dimensional arrangement and hemodynamics of mouse retinal
      microvessels. METHODS: Confocal microscopy was performed on fluorescein dextran
      filled retinal flatmounts. Capillary velocity in the deep layer was measured by
      epifluorescence intravital microscopy. The changes in the studied parameters
      after branch retinal vein occlusion were evaluated. RESULTS: The superficial and
      intermediate layers are both asymmetric crossroads for capillary blood flow, with
      approximately 70% of the capillary connections directing the flow from the
      arterioles into the deep layer. The venous flow from the deep layer joins the
      major veins in the superficial layer through transverse venules, indicating that
      major veins are directly connected to the deep layer. Red and white blood cell
      velocities +/- SD in the deep layer were 1.26 +/- 0.34 and 0.8 +/- 0.32 mm/sec
      respectively. After branch vein occlusion, venule dilation and decreased velocity
      were observed in the deep layer. CONCLUSIONS: In the mouse retina, a
      tridimensional model of retinal microcirculation was established, showing that
      most microvessel connections on the arteriolar side direct the flow from the
      superficial to the deep layer, and vice versa on the venular side. However, the
      presence of direct arteriovenous connections in the superficial layer and the
      longer vessel length in the deep layer offer the possibility of actively
      modulating intraretinal flow. Compared with other capillary beds, both the
      capillary velocity and microhematocrit are high, a situation that favors nutrient
      delivery to the inner retina.

PMID- 14578424
TI  - Alleviation of constant-light-induced photoreceptor degeneration by adaptation of
      adult albino rat to bright cyclic light.
AB  - PURPOSE: To further test the hypothesis that light-adaptation-mediated
      photoreceptor protection works through inhibition of apoptosis by activation
      and/or upregulation of neuroprotective molecules. METHODS: Albino rats were born
      and raised in 5-lux cyclic light (12 hours OFF and ON). At 8 weeks of age,
      animals were adapted to 400-lux cyclic light for different periods. Light damage
      was induced by exposure to constant light for 1 day at an illumination of 1700
      lux. Animals were killed, and their eyes were removed for morphometric and
      biochemical analysis. TUNEL assay was used to evaluate photoreceptor cell
      apoptosis and Western blot analyses were used to determine the levels of basic
      fibroblast growth factor (bFGF), neuronal nitric oxide synthase (nNOS), and
      caspase-3. RESULTS: Exposure of dim-reared rats to constant light for 1 day
      dramatically increased TUNEL-positive cells in the outer nuclear layer.
      Adaptation to 400-lux bright cyclic light for 4 days significantly reduced TUNEL
      positive cells induced by exposure to constant light, which correlated with a
      significant increase in bFGF expression. Compared with control retinas, caspase-3
      levels were not changed by exposure to constant light or after adaptation to 400
      lux. There was a significant increase in nNOS level in the constant-light-exposed
      group, but not in the group adapted to 400-lux bright light before exposure to
      constant light. CONCLUSIONS: The retina of the adult rat can rapidly upregulate
      neuroprotective mechanisms when switched from dim to bright cyclic light.
      Identification of the molecules involved in this process may allow rational
      development of therapeutic approaches to treat retinal degenerative diseases.

PMID- 14578425
TI  - Synaptic plasticity in mammalian photoreceptors prepared as sheets for retinal
      transplantation.
AB  - PURPOSE: To investigate systematically the early morphologic changes in axon
      terminals of adult mammalian rod and cone photoreceptors prepared as a sheet for
      subretinal transplantation. METHODS: An in vitro system was designed to maintain
      adult porcine retinas for up to 48 hours. Photoreceptor sheets, prepared by
      vibratome sectioning, and full-thickness retinas were cultured at temperatures
      similar to those in pretransplantation storage (4 degrees C) and after
      transplantation (37 degrees C). Changes in the outer nuclear and outer plexiform
      layers were analyzed, using immunohistochemistry, laser scanning confocal
      microscopy, and image analysis. RESULTS: Morphologic changes were observed in
      photoreceptor sheets as early as 10 minutes after incubation. The most
      significant change was the retraction of photoreceptor axons and terminals toward
      their cell bodies. Retraction was temperature dependent, being exacerbated at 37
      degrees C compared with 4 degrees C, at its maximum by 24 hours of culture, and
      present in sheets obtained from both superior and inferior retina. The cause of
      this movement was not preparation techniques associated with vibratome sectioning
      or gelatin removal. Retraction was also present in full-thickness neural retina
      incubated at 37 degrees C. Reduction in outer nuclear layer cell counts and
      thickness were also evident in these preparations, primarily in photoreceptor
      sheets. CONCLUSIONS: Adult photoreceptor sheets, a potential graft preparation
      for retinal transplantation, show a rapid retraction of axon terminals toward the
      cell bodies during culture. Although retraction may impede synaptic integration
      after transplantation, this intrinsic plasticity could be redirected to stimulate
      graft-host interaction.

PMID- 14578426
TI  - Periocular injection of microspheres containing PKC412 inhibits choroidal
      neovascularization in a porcine model.
AB  - PURPOSE: Oral administration of PKC412, a kinase inhibitor that blocks several
      isoforms of protein kinase C (PKC) and receptors for vascular endothelial growth
      factor (VEGF), platelet-derived growth factor, and stem cell factor, inhibits
      ocular neovascularization in a murine model. The purpose of this study was to
      determine whether sustained local delivery of PKC412 in a human-sized eye
      inhibits choroidal neovascularization (CNV). METHODS: Laser photocoagulation was
      used to rupture Bruch's membrane in young domestic pigs, and then a periocular
      injection of control microspheres or microspheres containing 25% or 50% PKC412
      was given. After 10 days the integrated area of CNV at Bruch's membrane rupture
      sites was measured by image analysis. The levels of PKC412 in choroid, retina,
      and vitreous were measured either 10 or 20 days after periocular injection of 50%
      PKC microspheres or at 20 days after injection of 25% PKC412 microspheres.
      RESULTS: The areas of CNV at Bruch's membrane rupture sites were significantly
      smaller in eyes that received a periocular injection of microspheres containing
      25% (P=0.0042) or 50% (P=0.0012) PKC412 than those in eyes injected with control
      microspheres. Ten days after periocular injection of 50% PKC412 microspheres,
      PKC412 was detected in the choroid, but not in the retina or vitreous. Twenty
      days after periocular injection of 50% PKC412, high levels of PKC412 were
      measured in the choroid, vitreous, and retina. Levels were lower but still
      substantial in all three compartments 20 days after periocular injection of 25%
      microspheres. CONCLUSIONS: Sustained local delivery of PKC412 provides a
      promising approach for treatment of CNV.

PMID- 14578427
TI  - FGF-2 antagonizes the TGF-beta1-mediated induction of pericyte alpha-smooth
      muscle actin expression: a role for myf-5 and Smad-mediated signaling pathways.
AB  - PURPOSE: Although the FGF and TGF-beta families are known to play an important
      role in regulating vascular endothelial and smooth muscle cell behavior, the
      influence of these matrix-binding growth factors on microvascular pericyte
      morphogenesis is not well understood. The current study was undertaken to examine
      the molecular mechanisms that mediate the effects of the endothelium-produced
      growth regulators FGF-2 and TGF-beta1 on retinal pericyte proliferation and
      contractile phenotype. METHODS: Using purified retinal pericytes, a series of
      assays were implemented, including RT-PCR, DNA binding, immunoprecipitation,
      electrophoretic mobility shift, and indirect immunofluorescence, in an attempt to
      elucidate the FGF/TGF-beta1 signaling cascades that mediate retinal microvascular
      cell growth and contractile phenotype. RESULTS: Treatment of retinal pericytes
      with FGF-2 and heparin stimulated nearly a log order increase in proliferation,
      whereas removal of FGF-2 or addition of TGF-beta1 caused withdrawal from the
      growth cycle, inducing a smooth-muscle-like contractile phenotype, as indicated
      by upregulation of alpha-smooth muscle actin (alpha-SMA). This switch from a
      growth-potentiated to a growth-arrested state followed induction of the
      transcriptional regulator myf-5, as well as the nuclear translocation of myf-5
      and Smad2. CONCLUSIONS: Several critical features of the endothelial cell
      extracellular matrix-pericyte molecular signaling axis were elucidated in the
      study that are likely to be responsible for regulating retinal microvascular
      morphogenesis during normal development, as well as the pathologic angiogenesis
      accompanying several ocular disorders, including diabetic retinopathy and age
      related macular degeneration.

PMID- 14578428
TI  - Differential distribution of harmonin isoforms and their possible role in Usher-1
      protein complexes in mammalian photoreceptor cells.
AB  - PURPOSE: Human Usher syndrome is the most common form of combined deafness and
      blindness. Usher type I (USH1), the most severe form, is characterized by
      profound congenital deafness, constant vestibular dysfunction, and prepubertal
      onset retinitis pigmentosa. Previous studies have shown that the USH1-proteins
      myosin VIIa, harmonin, and cadherin 23 interact and form a functional network
      during hair cell differentiation in the inner ear. The purpose of the present
      study was to analyze the molecular and cellular functions of these USH1 proteins
      in the mammalian retina. METHODS: Antibodies to USH1 proteins were generated and
      used in Western blot analysis of subcellular photoreceptor fractions and
      immunofluorescence and electron microscopy of the retina. RESULTS: Splice
      variants of harmonin were differentially expressed in the photoreceptor cell
      compartments. Whereas harmonin b isoforms were restricted to the light-sensitive
      outer segment, the harmonin a and c isoforms were more ubiquitously distributed
      in the photoreceptors. At the synaptic terminal of photoreceptor cells, harmonin
      a and c colocalized with myosin VIIa and cadherin 23. CONCLUSIONS: USH1 molecules
      can assemble to a supramolecular complex at photoreceptor synapses. Such a
      complex may contribute to the cortical cytoskeletal matrices of the pre- and
      postsynaptic regions, which are thought to play a fundamental role in the
      organization of synaptic junctions. Dysfunction of any of the USH1 complex
      partners may lead to synaptic dysfunction causing retinitis pigmentosa, the
      clinical phenotype in the retina of patients with USH1. Furthermore, in
      photoreceptor outer segments, harmonin may also contribute to the clustering of
      outer segment proteins into supramolecular complexes.

PMID- 14578429
TI  - Dyslipidemia, but not hyperglycemia, induces inflammatory adhesion molecules in
      human retinal vascular endothelial cells.
AB  - PURPOSE: The initial determinants of retinal microvascular damage in diabetic
      retinopathy are not well understood, but are likely to be induced by
      hyperglycemia and/or dyslipidemia. The purpose of this study was to examine the
      effect of fatty acids and hyperglycemia on human retinal vascular endothelial
      (hRVE) cells as a means of mimicking diabetic metabolic disorders. METHODS: The
      expression of adhesion molecules in hRVE and human umbilical vein endothelial
      cells (HUVECs) was assayed by Western blot analysis and confirmed by leukocyte
      adhesion assay. The mechanisms underlying the induction of adhesion molecules by
      fatty acids were further investigated by using cyclooxygenase (COX), lipoxygenase
      (LOX), and P450 monooxygenase (MOX) inhibitors. RESULTS: Treatment of hRVE cells
      with the n6 polyunsaturated fatty acids (PUFAs) 18:2n6 and 20:4n6 for up to 24
      hours resulted in a significant induction of intercellular adhesion molecule
      (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 protein levels. In
      contrast, treatment with high glucose (22 mM) for 24 hours did not affect CAM
      expression. Induction of CAM by n6 PUFA correlated with enhanced leukocyte
      binding to hRVE cells. The effect of n6 PUFA on ICAM-1 and VCAM-1 was blocked by
      an inhibitor of LOX, but not by COX or MOX inhibitors. In contrast to hRVE cells,
      n6 PUFA did not induce ICAM-1 or VCAM-1 in HUVECs. CONCLUSIONS: The data obtained
      in this study demonstrate that acute exposure to linoleic or arachidonic acid,
      but not hyperglycemia, induces inflammatory adhesion molecule expression in the
      presence of LOX in microvascular hRVE cells, but not in HUVECs. These results are
      consistent with the emerging hypothesis recognizing early-stage diabetic
      retinopathy as a low-grade chronic inflammatory disease.

PMID- 14578431
TI  - Normal intersubject threshold variability and normal limits of the SITA SWAP and
      full threshold SWAP perimetric programs.
AB  - PURPOSE: To compare intersubject variability and normal limits of threshold
      values between the new Swedish interactive test algorithm short wavelength
      automated perimetry (SITA SWAP) and the older Full Threshold SWAP programs (Carl
      Zeiss Meditec, Dublin, CA). METHODS: Normal reduction of differential light
      sensitivity with age, age-corrected thresholds, intersubject variability, and
      normal limits of sensitivity were calculated from SITA SWAP and Full Threshold
      SWAP fields obtained in 53 normal subjects between 20 and 72 years of age.
      RESULTS: Age influence on threshold sensitivity was the same with the two SWAP
      programs. On average, sensitivity decreased by 0.13 dB per year of age. Age
      corrected normal threshold sensitivity was significantly higher (P<0.0001) for
      SITA SWAP than for Full Threshold SWAP. The means for a subject 45.4 years of age
      were 28.8 dB with SITA SWAP and 24.4 dB with Full Threshold SWAP. Intersubject
      variance was 22% smaller with SITA SWAP than with Full Threshold SWAP. Normal
      limits at the P<5% significance level were, on average, 14% narrower with SITA
      SWAP than with Full Threshold SWAP using Total Deviations from age-corrected
      normal thresholds and 11% narrower when applying Pattern Deviation, which is
      intended to adjust for general depression or elevation of the field. CONCLUSIONS:
      SITA SWAP test results from normal eyes showed higher sensitivities than results
      from the older Full Threshold SWAP. This represents an increase of the dynamic
      range, which implies that more patients can be tested with SWAP. The smaller
      intersubject variability with SITA SWAP means narrower normal limits and may be
      associated with more sensitive probability maps.

PMID- 14578430
TI  - Prevention of ornithine cytotoxicity by nonpolar side chain amino acids in
      retinal pigment epithelial cells.
AB  - PURPOSE: To investigate the effect of amino acids on ornithine cytotoxicity in
      ornithine-delta-aminotransferase (OAT)-deficient human retinal pigment epithelial
      (RPE) cells as an in vitro model of gyrate atrophy (GA) of the choroid and
      retina. METHODS: RPE cells were treated with 0.5 mM 5-fluoromethylornithine (5
      FMOrn), a specific and irreversible OAT inhibitor. OAT-deficient RPE cells were
      incubated with 10 mM ornithine in the presence of 20 mM of 1 of 18 amino acids or
      10 mM 2-amino-2-norbornane-carboxylic acid (BCH), a conventional inhibitor of the
      amino acid transporter system L. Ornithine cytotoxicity and cytoprotective
      effects of each amino acid was evaluated with a 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) colorimetric assay 72 hours after treatment
      with ornithine in OAT-deficient RPE cells. Ornithine incorporation into RPE cells
      was evaluated using DL-[14C]ornithine. RESULTS: An MTT colorimetric assay
      revealed that small and large zwitterionic amino acids, but not acidic or basic
      amino acids, decreased ornithine cytotoxicity in OAT-deficient RPE cells.
      Incorporation of DL-[14C]ornithine by RPE cells decreased to 79% of the control
      level after incubation for 48 hours with 20 mM leucine, the most effective
      cytoprotective amino acid. Further, BCH prevented ornithine cytotoxicity in a
      dose-dependent manner. Both light and heavy chains of L-type amino acid
      transporter (LAT)-1, LAT2, y+LAT1, and 4F2hc were expressed in RPE cells.
      CONCLUSIONS: The present results demonstrate that L-type amino acid
      transporter(s) may be involved in protection against ornithine cytotoxicity in
      human RPE cells. Thus, amino acid transportation in RPE cells may be a good
      target for a new therapy for GA as well as other kinds of chorioretinal
      degeneration.

PMID- 14578432
TI  - Facial recognition using simulated prosthetic pixelized vision.
AB  - PURPOSE: To evaluate a model of simulated pixelized prosthetic vision using
      noncontiguous circular phosphenes, to test the effects of phosphene and grid
      parameters on facial recognition. METHODS: A video headset was used to view a
      reference set of four faces, followed by a partially averted image of one of
      those faces viewed through a square pixelizing grid that contained 10x10 to 32x32
      dots separated by gaps. The grid size, dot size, gap width, dot dropout rate, and
      gray-scale resolution were varied separately about a standard test condition, for
      a total of 16 conditions. All tests were first performed at 99% contrast and then
      repeated at 12.5% contrast. RESULTS: Discrimination speed and performance were
      influenced by all stimulus parameters. The subjects achieved highly significant
      facial recognition accuracy for all high-contrast tests except for grids with 70%
      random dot dropout and two gray levels. In low-contrast tests, significant facial
      recognition accuracy was achieved for all but the most adverse grid parameters:
      total grid area less than 17% of the target image, 70% dropout, four or fewer
      gray levels, and a gap of 40.5 arcmin. For difficult test conditions, a
      pronounced learning effect was noticed during high-contrast trials, and a more
      subtle practice effect on timing was evident during subsequent low-contrast
      trials. CONCLUSIONS: These findings suggest that reliable face recognition with
      crude pixelized grids can be learned and may be possible, even with a crude
      visual prosthesis.

PMID- 14578433
TI  - Anatomy of a supergroup: does a criterion of normal perimetric performance
      generate a supernormal population?
AB  - PURPOSE: To interpret individual results from automated perimeters, a normative
      database must be developed. Typically, a set of criteria determines those
      subjects that may be included in the database. This study examined whether a
      criterion of normal performance on an established perimeter generates a subgroup
      with supernormal perimetric performance. METHODS: The right-eye perimetric
      results of 100 subjects were analyzed. Subjects had visual acuities of 6/12 or
      better, no history of eye disease, and normal slit lamp biomicroscopic and
      ophthalmoscopic examinations. Subjects performed test-retest visual field
      examinations on a Humphrey Field Analyzer (HFA) 24-2 test (Zeiss Humphrey
      Systems, Dublin, CA), and on a custom frequency-doubling (FD) perimeter with
      targets spaced in the same 24-2 pattern. RESULTS: Test-retest correlation
      (Spearman rank correlation coefficients, rs) for mean defect (MD) and pattern SD
      (PSD) were 0.65 and 0.40 (HFA), and 0.82 and 0.39 (FD perimeter). Three subjects
      with HFA MDs in the lower 5% had similarly low MDs on retest, whereas no subject
      was common between the test and retest for the lower 5% of HFA PSD. Correlation
      between the HFA and FD test results were 0.41 (MD) and 0.05 (PSD). Based on these
      correlations, the bias introduced into perimetric probability limits were
      determined, by using Monte Carlo simulations. CONCLUSIONS: Although a criterion
      of a normal MD may produce a subpopulation with supernormal perimetric
      performance, a criterion of a normal PSD is less likely to do so. Also, a
      criterion on one test type is less likely to create a supernormal group on a
      different test type. The bias introduced into perimetric probability limits is
      small.

PMID- 14578434
TI  - Efficiency of temporal integration of sinusoidal flicker.
AB  - PURPOSE: Detection efficiency for flickering stimuli of constant duration
      decreases with increasing temporal frequency. Increasing frequency in this case
      also implies increasing number of flicker cycles. The current study was conducted
      to investigate whether this result could be due to the limited ability of the
      central detector to integrate flicker cycles. METHODS: Flicker sensitivity was
      measured at 1 to 20 Hz in strong external temporal noise with increasing stimulus
      duration. RESULTS: Sensitivity increased with stimulus duration in a
      nonsaturating manner up to the longest exposure times used, indicating
      probability summation. When expressed in terms of detection efficiency (eta) as a
      function of number of cycles presented (n) all data could be modeled as a single
      decreasing function of the form eta=0.29n(-0.70). CONCLUSIONS: The results show
      that the number of cycles, not time, is the determinant of probability summation
      of flicker. The results are consistent with the idea that the central detector is
      a suboptimal matched filter spanning less than one cycle.

PMID- 14578435
TI  - Spontaneous pneumothorax: an unusual presentation of rheumatoid arthritis.

PMID- 14578436
TI  - Renal microinfarction in Behcet's disease.

PMID- 14578437
TI  - Exercise-induced urticarial vasculitis as a paraneoplastic manifestation of
      cystic teratoma.

PMID- 14578438
TI  - Early-onset polyarthritis as presenting feature of intestinal infection with
      Strongyloides stercoralis.

PMID- 14578440
TI  - The GALS examination.

PMID- 14578439
TI  - Musculoskeletal examination for medical students.

PMID- 14578442
TI  - DISHphagia--a difficult problem to swallow.

PMID- 14578443
TI  - Musculoskeletal examination for children and adolescents: do standard textbooks
      contain enough information?

PMID- 14578445
TI  - Lessons to be learned: review of a multidisciplinary foot clinic in rheumatology.

PMID- 14578444
TI  - Anti-TNF treatment in secondary amyloidosis.

PMID- 14578446
TI  - Kawasaki-like syndrome in an HIV-infected adult.

PMID- 14578447
TI  - Osteoclastic bone resorption in rheumatoid arthritis and the acute-phase
      response.

PMID- 14578449
TI  - Histone sumoylation is associated with transcriptional repression.
AB  - Histone proteins are subject to modifications, such as acetylation, methylation,
      phosphorylation, ubiquitination, glycosylation, and ADP ribosylation, some of
      which are known to play important roles in the regulation of chromatin structure
      and function. Here we report that histone H4 is modified by small ubiquitin
      related modifier (SUMO) family proteins both in vivo and in vitro. H4 binds to
      the SUMO-conjugating enzyme (E2), UBC9, and can be sumoylated in an E1 (SUMO
      activating enzyme)- and E2-dependent manner. We present evidence suggesting that
      histone sumoylation mediates gene silencing through recruitment of histone
      deacetylase and heterochromatin protein 1.

PMID- 14578450
TI  - Axonal transport of eukaryotic translation elongation factor 1alpha mRNA couples
      transcription in the nucleus to long-term facilitation at the synapse.
AB  - Long-term synaptic plasticity requires both gene expression in the nucleus and
      local protein synthesis at synapses. The effector proteins that link molecular
      events in the cell body with local maintenance of synaptic strength are not
      known. We now show that treatment with serotonin (5-HT) that produces long-term
      facilitation induces the Aplysia eukaryotic translation elongation factor 1alpha
      (Ap-eEF1A) as a late gene that might serve this coupling function in sensory
      neurons. Although the translation factor is induced, it is not transported into
      axon processes when the stimulation with 5-HT was restricted to the cell body. In
      contrast, its mRNA is transported when 5-HT was applied to both cell body and
      synapses. Intracellular injection of antisense oligonucleotides or antibodies
      that block the induction and expression of Ap-eEF1A do not affect the initial
      expression of long-term facilitation but do block its maintenance beyond 24 h.
      The transport of eEF1A protein and its mRNA to nerve terminals suggests that the
      translation factor plays a role in the local protein synthesis that is essential
      for maintaining newly formed synapses.

PMID- 14578451
TI  - Id-1 as a molecular target in therapy for breast cancer cell invasion and
      metastasis.
AB  - Mammary epithelial cells constitutively expressing Id-1 protein are unable to
      differentiate, acquire the ability to proliferate, and invade the extracellular
      matrix. In addition, Id-1 is aberrantly over-expressed in aggressive and
      metastatic breast cancer cells, as well as in human breast tumor biopsies from
      infiltrating carcinomas, suggesting Id-1 might be an important regulator of
      breast cancer progression. We show that human metastatic breast cancer cells
      become significantly less invasive in vitro and less metastatic in vivo when Id-1
      is down-regulated by stable transduction with antisense Id-1. Expression of the
      matrix metalloproteinase MT1-MMP is decreased in proportion to the decrease in Id
      1 protein levels, representing a potential mechanism for the reduction of
      invasiveness. Further, to more accurately recapitulate the biology of and
      potential therapeutic approaches to tumor metastasis, we targeted Id-1 expression
      systemically in tumor-bearing mice by using a nonviral approach. We demonstrate
      significant reduction of both Id-1 and MT1-MMP expressions as well as the
      metastatic spread of 4T1 breast cancer cells in syngeneic BALB/c mice. In
      conclusion, our studies have identified Id-1 as a critical regulator of breast
      cancer progression and suggest the feasibility of developing novel therapeutic
      approaches to target Id-1 expression to reduce breast cancer metastasis in
      humans.

PMID- 14578452
TI  - Hyposulfatemia, growth retardation, reduced fertility, and seizures in mice
      lacking a functional NaSi-1 gene.
AB  - Inorganic sulfate is required for numerous functions in mammalian physiology, and
      its circulating levels are proposed to be maintained by the Na+-SO42-
      cotransporter, (NaSi-1). To determine the role of NaSi-1 in sulfate homeostasis
      and the physiological consequences in its absence, we have generated a mouse
      lacking a functional NaSi-1 gene, Nas1. Serum sulfate concentration was reduced
      by >75% in Nas1-/- mice when compared with Nas1+/+ mice. Nas1-/- mice exhibit
      increased urinary sulfate excretion, reduced renal and intestinal Na+-SO42-
      cotransport, and a general growth retardation. Nas1-/- mouse body weight was
      reduced by >20% when compared with Nas1+/+ and Nas1+/- littermates at 2 weeks of
      age and remained so throughout adulthood. Nas1-/- females had a lowered
      fertility, with a 60% reduction in litter size. Spontaneous clonic seizures were
      observed in Nas1-/- mice from 8 months of age. These data demonstrate NaSi-1 is
      essential for maintaining sulfate homeostasis, and its expression is necessary
      for a wide range of physiological functions.

PMID- 14578453
TI  - Premature telomeric loss in rheumatoid arthritis is genetically determined and
      involves both myeloid and lymphoid cell lineages.
AB  - In rheumatoid arthritis, peripheral blood T cells have age-inappropriate
      telomeric erosion. We examined whether HLA-DRB1*04 alleles, the major
      susceptibility genes for this disease, confer risk for T cell senescence. In
      healthy individuals, HLA-DRB1*04 alleles were associated with excessive loss of
      telomeres in CD4+ T cells. Accelerated telomeric erosion occurred during the
      first two decades of life and was followed by reduced homeostatic T cell
      proliferation during adulthood. Premature telomeric loss also affected
      granulocytes, suggesting that the hematopoietic stem cell is the primary target.
      Telomeric repair mechanisms were intact in HLA-DRB1*04+ donors. We propose that
      HLA-DRB1*04 alleles or genes in linkage disequilibrium regulate stem cell
      replication and contribute to the accumulation of senescent and autoreactive T
      cells in rheumatoid arthritis.

PMID- 14578456
TI  - 'Fishing' out a long distance regulator of the sonic hedgehog gene associated
      with preaxial polydactyly.

PMID- 14578454
TI  - Isorhodopsin rather than rhodopsin mediates rod function in RPE65 knock-out mice.
AB  - The chromophore of visual pigments is 11-cis-retinal and, thus, in its absence,
      opsin is not photosensitive and no visual function exists. However, in the RPE65
      knockout (Rpe65-/-) mouse, where synthesis of 11-cis-retinal does not occur, a
      minimal visual response from rod photoreceptors is obtained. We have examined if
      an alternative pathway exists for cis-retinoid generation in the absence of
      RPE65. Cyclic-light-reared, 2-month-old Rpe65-/- mice were placed in complete
      darkness. No exogenous retinoids were administered. After 4 weeks, enhanced a-
      and b-wave amplitudes were obtained, increasing >10-fold for the a-wave and >3
      fold for the b-wave as compared with cyclic-light-reared Rpe65-/- mice. Visual
      pigment levels increased to approximately 10 pmol per retina, compared with no
      measurable pigment for cyclic-light-reared Rpe65-/- mice. The lambdamax of the
      isolated pigment was 487 nm, characteristic for isorhodopsin. Retinoid
      extractions confirmed the presence of 9-cis-retinal and the absence of 11-cis
      retinal. Once the Rpe65-/- mice were returned to cyclic light, within 48 h the
      electroretinogram function returned to levels found in Rpe65-/- mice maintained
      in cyclic light. This dark-mediated pathway is also operational in older animals,
      because 13-month-old Rpe65-/- mice kept in prolonged darkness (12 weeks) had
      increased isorhodopsin levels and electroretinogram a- and b-wave amplitudes.
      These studies demonstrate that a pathway exists in the eye for the generation of
      9-cis-retinal that is independent of RPE65 and light.

PMID- 14578455
TI  - Saccharomyces cerevisiae phenotypes can be predicted by using constraint-based
      analysis of a genome-scale reconstructed metabolic network.
AB  - Full genome sequences of prokaryotic organisms have led to reconstruction of
      genome-scale metabolic networks and in silico computation of their integrated
      functions. The first genome-scale metabolic reconstruction for a eukaryotic cell,
      Saccharomyces cerevisiae, consisting of 1,175 metabolic reactions and 733
      metabolites, has appeared. A constraint-based in silico analysis procedure was
      used to compute properties of the S. cerevisiae metabolic network. The computed
      number of ATP molecules produced per pair of electrons donated to the electron
      transport system (ETS) and energy-maintenance requirements were quantitatively in
      agreement with experimental results. Computed whole-cell functions of growth and
      metabolic by-product secretion in aerobic and anaerobic culture were consistent
      with experimental data, and thus mRNA expression profiles during metabolic shifts
      were computed. The computed consequences of gene knockouts on growth phenotypes
      were consistent with experimental observations. Thus, constraint-based analysis
      of a genome-scale metabolic network for the eukaryotic S. cerevisiae allows for
      computation of its integrated functions, producing in silico results that were
      consistent with observed phenotypic functions for approximately 70-80% of the
      conditions considered.

PMID- 14578458
TI  - A fluorine-labeled methotrexate as a probe for monitoring tumor antifolate
      pharmacokinetics: synthesis, in vitro cytotoxicity, and pilot in vivo 19F
      magnetic resonance spectra.
AB  - The synthesis and characterization of 3'-fluoromethotrexate (FMTX), a novel
      fluorine-labeled analogue of methotrexate, are presented. Molecular modeling
      studies indicate that the fluorine atom causes only minimal changes in the
      structure/binding in the complex of the antifolate with thymidine synthetase and
      dihydrofolate reductase (DHFR). The in vitro cytotoxicity of this compound is
      shown to be equivalent to that of the parent antifolate compound. While the focus
      of this report is the synthetic technique of FMTX, it is also demonstrated that
      tumor accumulation of the labeled compound in vivo can be observed via 19F
      magnetic resonance spectroscopy (MRS) in a human tumor xenograft model.

PMID- 14578459
TI  - Atorvastatin prevents RhoC isoprenylation, invasion, and metastasis in human
      melanoma cells.
AB  - Melanoma is a deadly cancer due to its propensity to metastasize. Pharmacological
      inhibition of cell motility may benefit patients with cutaneous melanoma by
      preventing metastasis to internal organs. The Rho GTPases are signaling molecules
      that drive metastasis by controlling cell motility. We found RhoC to be expressed
      in clinical melanoma specimens and hypothesized that inhibiting its activation
      might prevent metastasis. Some Rho proteins, such as RhoC, depend on
      posttranslational geranylgeranylation for biological activity. We investigated
      the effect that Atorvastatin, a 3-hydroxy 3-methylglutaryl CoA (HMG-CoA)
      reductase inhibitor that prevents Rho geranylgeranylation, had on subcellular
      localization and activity of Rho proteins as well as the metastatic ability of
      melanoma cells. Atorvastatin inhibited Rho activation and reverted the metastatic
      phenotype of human melanoma cells in vitro. Moreover, Atorvastatin, at plasma
      levels comparable to those used to treat of hypercholesterolemia, inhibited in
      vivo metastasis of melanoma cells overexpressing RhoC. These results support
      further examination of statins for primary prophylaxis of melanoma metastasis.

PMID- 14578460
TI  - Mechanistic studies of a novel human fusion toxin composed of vascular
      endothelial growth factor (VEGF)121 and the serine protease granzyme B: directed
      apoptotic events in vascular endothelial cells.
AB  - The serine protease granzyme B (GrB; 25 kDa) is capable of inducing apoptosis
      through both caspase-dependent and caspase-independent mechanisms. We designed a
      novel vascular-targeting fusion construct designated as GrB/vascular endothelial
      growth factor (VEGF)121, which is composed of a non-heparin-binding isoform of
      VEGF and the proapoptotic pathway enzyme GrB fused via a short, flexible tether
      (G4S). The chimeric fusion gene was then cloned into a bacterial vector, and the
      protein was expressed in Escherichia coli and purified by nickel-NTA metal
      affinity chromatography. Western blotting confirmed incorporation of both VEGF121
      and GrB proteins into the construct. GrB/VEGF121 specifically bound (ELISA) to
      porcine aortic endothelial (PAE)/FLK-1 cells overexpressing the FLK-1/KDR
      receptor but not to cells overexpressing the FLT-1 receptor. Immunofluoresence
      studies showed that the GrB moiety of GrB/VEGF121 was delivered efficiently and
      rapidly into the cytosol of PAE/FLK-1 cells but not into that of PAE/FLT-1 cells
      after 4 h treatment with GrB/VEGF121. Treatment of cells with GrB/VEGF121 showed
      that the IC50 was approximately 10 nM against PAE/FLK-1 cells; however, there
      were no cytotoxic effects observed on PAE/FLT-1 cells at doses up to 200 nM.
      GrB/VEGF121 induced apoptotic events specifically on PAE/FLK-1 as assessed by
      terminal deoxynucleotidyl transferase-mediated nick end labeling assay, DNA
      laddering, and cytochrome c release from mitochondria. In addition, the fusion
      construct mediated the cleavage of caspase-8, caspase-3, and poly(ADP-ribose)
      polymerase in target endothelial cells within 4 h after treatment. In conclusion,
      delivery of the human proapoptotic pathway enzyme GrB to tumor vascular
      endothelial cells or to tumor cells may have significant therapeutic potential
      and represents a potent new class of targeted therapeutic agents with a unique
      mechanism of action.

PMID- 14578461
TI  - p16 gene therapy: a potentially efficacious modality for nasopharyngeal
      carcinoma.
AB  - p16 is an important regulator of the cell cycle at the G(1) phase. Frequent
      aberration of p16 in nasopharyngeal carcinoma (NPC) suggests a role for this
      tumor suppressor gene in disease development. p16 gene transfer has been
      demonstrated to be effective in various human cancer models, including breast,
      lung, and prostate, causing cell cycle arrest, apoptosis, and tumor growth delay.
      We investigated the potential of adenoviral-mediated p16 therapy, in combination
      with ionizing radiation (RT), in two distinct NPC models. Two deltaE1 adenoviral
      vectors were employed: one carrying the human p16 gene (adv.p16), and the other a
      beta-galactosidase reporter gene (adv.beta-gal), both driven by the
      cytomegalovirus (CMV) promoter. Two NPC cell lines with differential endogenous
      p16 expression, CNE-1 (low) and CNE-2Z (high), were evaluated for protein
      expression, cytotoxicity, cell cycle analysis, apoptosis, and senescence. The CNE
      1 cells were exquisitely sensitive to adv.p16, with 0.1% survival level after
      gene therapy [25 plaque-forming unit (pfu)/cell], which further decreased to
      0.01% with the addition of RT (2 Gy). This reduction in survival was effected
      through necrosis, G1 arrest, and senescence. In contrast, CNE-2Z cells were
      resistant to adv.p16 gene transfer, with 75% surviving at an equivalent viral
      dose. This differential sensitivity was recapitulated in vivo in that adv.p16
      treated CNE-1 cells formed no tumors in severe-combined-immunodeficiency (SCID)
      mice, followed for over 100 days. In contrast, tumor formation was detected 40
      days after implantation of adv.p16-treated CNE-2Z cells. In conclusion, adv.p16
      gene transfer appears to be highly effective against NPC that lack functional
      p16, which is the situation in the majority of NPC patients.

PMID- 14578462
TI  - Histone deacetylase inhibitor LAQ824 down-regulates Her-2 and sensitizes human
      breast cancer cells to trastuzumab, taxotere, gemcitabine, and epothilone B.
AB  - Histone deacetylase inhibitors induce hyperacetylation of the amino-terminal
      lysine residues of the core nucleosomal histones, which results in chromatin
      remodeling and altered gene expression. Present studies demonstrate that exposure
      to a novel hydroxamic acid analogue histone deacetylase inhibitor, LAQ824,
      induced p21WAF1 and p27KIP1 and caused growth arrest and apoptosis of human
      breast cancer SKBR-3 and BT-474 cells that possess amplification and
      overexpression of Her-2/neu. Treatment with LAQ824 depleted the mRNA and protein
      levels of Her-2/neu-encoded Her-2, which was associated with attenuation of pAKT,
      c-Raf-1, and phosphorylated mitogen-activated protein kinase levels. LAQ824 also
      induced the acetylation of heat shock protein (hsp) 90, resulting in inhibition
      of its binding to ATP, which has been shown to impair the chaperone association
      of hsp 90 with its client proteins, Her-2, AKT, and c-Raf-1. Consistent with
      this, treatment with LAQ824 shifted the binding of Her-2 from hsp 90 to hsp 70,
      promoting proteasomal degradation of Her-2. Thus, LAQ824 depletes Her-2 through
      two mechanisms: attenuation of its mRNA levels and promotion of its degradation
      by the proteasome. Following LAQ824 treatment, the cell membrane association,
      autotyrosine phosphorylation, and colocalization of Her-2 with HER-3 also
      declined. Cotreatment with LAQ824 significantly increased trastuzumab-induced
      apoptosis of BT-474 and SKBR-3 cells. This was associated with greater
      attenuation of Her-2, c-Raf-1, and pAKT levels. LAQ824 also enhanced taxotere
      induced, epothilone B-induced, and gemcitabine-induced apoptosis of BT-474 and
      SKBR-3 cells. These findings suggest that LAQ824 is active against human breast
      cancer cells and has the potential to improve the efficacy of trastuzumab,
      taxotere, gemcitabine, and epothilone B against breast cancer with Her
      2/neuamplification.

PMID- 14578463
TI  - Antisense inhibition of laminin-8 expression reduces invasion of human gliomas in
      vitro.
AB  - Using gene array technology, we recently observed for the first time an up
      regulation of laminin alpha4 chain in human gliomas. The data were validated by
      semiquantitative reverse transcription-PCR for RNA expression and
      immunohistochemistry for protein expression. Moreover, increase of the alpha4
      chain-containing laminin-8 correlated with poor prognosis for patients with brain
      gliomas. Therefore, we hypothesized that inhibition of laminin-8 expression by a
      new generation of highly specific and stable antisense oligonucleotides
      (Morpholino) against chains of laminin-8 could slow or stop the spread of glioma
      and its recurrence and thus might be a promising approach for glioma therapy. We
      next sought to establish an in vitro model to test the feasibility of this
      approach and to optimize conditions for Morpholino treatment. To develop a model,
      we used human glioblastoma multiforme cell lines M059K and U-87MG cocultured with
      normal human brain microvascular endothelial cells (HBMVEC). Using Western blot
      analysis and immunohistochemistry, we confirmed that antisense treatment
      effectively blocked laminin-8 protein synthesis. Antisense oligonucleotides
      against both alpha4 and beta1 chains of laminin-8 were able to block
      significantly the invasion of cocultures through Matrigel. On average, the
      invasion was blocked by 62% in cocultures of U-87MG with HBMVEC and by 53% in
      cocultures of M059K with HBMVEC. The results show that laminin-8 may contribute
      to glioma progression and recurrence not only as part of the neovascularization
      process but also by directly increasing the invasive potential of tumor cells.

PMID- 14578464
TI  - Plasmid-based vaccines encoding rat neu and immune stimulatory molecules can
      elicit rat neu-specific immunity.
AB  - DNA vaccines are ideally suited for immunizing against tumor antigens because
      constructs can be formulated that not only encode the tumor antigen but also
      encode molecules chosen to improve the ability to elicit an antitumor response.
      Ligands expressed on antigen-presenting cells associated with stimulating a
      robust T-cell response are excellent candidates for inclusion in a DNA vaccine.
      Mice transgenic for the HER-2/neu homologue, rat neu, were immunized with full
      length rat neu cDNA given alone or in combination with plasmids encoding
      costimulatory molecules CD80 or CD86 and the ligand for CD137 (CD137L).
      Intradermal injection of the plasmid constructs resulted in both plasmid
      transcript and antigen protein expression being detected in lymph nodes draining
      the injection site. Immunization with plasmids encoding the neu antigen along
      with plasmids encoding CD137L and either CD80 or CD86 resulted in the generation
      of neu-specific antibodies that induced phopshorylation of the neu tyrosine
      kinase and inhibited the growth of cultured tumor cells overexpressing neu.
      Survival of animals was significantly prolonged after immunization with vaccines
      encoding neu together with the costimulatory molecules. Although tumors
      eventually occurred in the vaccinated animals, they were markedly infiltrated
      with CD4+ T cells. DNA vaccines encoding neu, when given in combination with both
      CD137L and either CD80 or CD86, can induce cellular and humoral immunity and
      result in an antitumor effect.

PMID- 14578465
TI  - Carcinoembryonic antigen-producing cell-specific oncolytic adenovirus, OV798, for
      colorectal cancer therapy.
AB  - Human carcinoembryonic antigen (CEA) is overexpressed in most colorectal cancers
      and has been widely used as a clinical marker for the management of colon cancer
      patients. The transcriptional regulatory elements (TREs) of CEA include two
      enhancer elements and a promoter in the 5'-flanking region of the CEA gene. By
      using these elements in different combinations to control reporter gene
      expression and the replication of adenovirus variants in various tumor cells, we
      have identified an optimal CEA regulatory cassette that tightly controls gene
      expression and viral replication in CEA-producing colon cancer cells. One of
      these variants, OV798, in which this regulatory cassette controls E1A expression,
      was further characterized. OV798 preferentially replicates in and kills CEA
      producing colorectal cancer cell lines such as LoVo and SW1463, but its
      replication is attenuated by 1000-fold in the CEA-negative cell lines Colo-320DM
      (colon cancer), PA-1 (ovarian cancer), G361 (melanoma), U118 MG (glioma), and HBL
      100 (human breast epithelial cell). The antitumor activity of OV798 was further
      examined in BALB/c nu/nu mice carrying s.c. human colon tumor xenografts. A
      single intratumoral administration of OV798 resulted in growth inhibition of
      human LoVo colon cancer xenografts. Six weeks after treatment, relative tumor
      volume decreased to 90% of baseline for the OV798 treatment group, compared to an
      increase to 1200% of baseline at 4 weeks for the vehicle-treated group. In vitro
      and in vivo characterization indicate that OV798 could be used as a therapy for
      human colon cancer.

PMID- 14578466
TI  - Preclinical evaluation of the tyrosine kinase inhibitor SU11248 as a single agent
      and in combination with "standard of care" therapeutic agents for the treatment
      of breast cancer.
AB  - SU11248 is an oral multitargeted tyrosine kinase inhibitor with antitumor and
      antiangiogenic activities through targeting platelet-derived growth factor
      receptor, vascular endothelial growth factor receptor, KIT, and FLT3, the first
      three of which are expressed in human breast cancer and/or its supporting
      tissues. The purpose of the present studies was to demonstrate the potent
      anticancer activity of SU11248 alone or in combination with conventional
      cytotoxic agents against several distinct preclinical models of breast cancer.
      SU11248 was administered as a monotherapy to (1) mouse mammary tumor virus-v-Ha
      ras mice and 7,12-dimethylbenz(a)anthracene-treated rats bearing mammary tumors
      and (2) mice bearing human breast cancer xenografts of s.c. MX-1 tumors and
      osseous metastasis of a MDA-MB-435-derived cell line (435/HAL-Luc). SU11248 was
      also administered in combination with docetaxel both in xenograft models and in
      combination with 5-fluorouracil and doxorubicin in the MX-1 model. SU11248
      treatment potently regressed growth of mammary cancers in mouse mammary tumor
      virus-v-Ha-ras transgenic mice (82% regression) and 7,12
      dimethylbenz(a)anthracene-induced mammary tumors in rats (99% regression at the
      highest dose; P < 0.05 for both). This agent also inhibited MX-1 tumor growth by
      52%, with markedly enhanced anticancer effects when administered in combination
      with docetaxel, 5-fluorouracil, or doxorubicin compared with either agent alone
      (P < 0.05). SU11248 treatment in combination with docetaxel effectively prolonged
      survival of mice, with 435/HAL-Luc cancer xenografts established in bone compared
      with either agent alone (P < 0.05). These results demonstrate that SU11248 is
      effective in preclinical breast cancer models and suggest that it may be useful
      in the treatment of breast cancer in the clinic.

PMID- 14578467
TI  - Macrophage inhibitory cytokine-1: a novel biomarker for p53 pathway activation.
AB  - The p53 tumor suppressor protein plays a key function in the cellular response to
      stress by activating a subset of genes responsible for cell cycle arrest and
      apoptosis. Activation of the p53 pathway in tumor cells has been proposed as a
      novel approach to cancer therapy and substantial efforts have been dedicated to
      the discovery of pharmacological p53 activators. Here, we show that the
      transforming growth factor-beta superfamily cytokine, macrophage inhibitory
      cytokine-1 (MIC-1), can serve as a secreted biomarker for activation of p53 in
      both cellular and xenograft models of human cancer. Using doxorubicin treatment
      in the HCT116 colon cancer cell line, we have shown that MIC-1 secretion into
      culture media is correlated with p53 pathway activation as measured by the up
      regulation of its downstream transcriptional target p21. When transplanted into
      nude mice, HCT116 cells continued to secret human MIC-1 and mouse plasma levels
      correlated well with tumor volume. Treatment of these animals with a single dose
      of doxorubicin led to activation of the p53 pathway and a nearly 4-fold elevation
      of the plasma MIC-1 level, which was paralleled by p21 induction in the tumor
      xenografts. Estimation of MIC-1 concentration, both in vivo and in vitro,
      represents a novel tool for the study of p53 pathway and development of p53
      activating therapeutics.

PMID- 14578469
TI  - Selected isothiocyanates rapidly induce growth inhibition of cancer cells.
AB  - Many plant-derived isothiocyanates (ITCs), which occur in human diet, are potent
      cancer chemopreventive agents in animals. Among the anticarcinogenic mechanisms
      that have been revealed for ITCs is the inhibition of cell proliferation. We
      report that exposure of cancer cells to either allyl-ITC (AITC), benzyl-ITC
      (BITC), or phenethyl-ITC (PEITC) for only 3 h was long enough for the inhibition
      of cell growth, based on a comparison of IC50 values; regardless of the origin of
      cancer cells; and even in drug-resistant cells that overexpressed multidrug
      resistance associated protein-1 (MRP-1) or P-glycoprotein-1 (Pgp-1). In contrast,
      the inhibitory effect of another ITC, sulforaphane (SF), on these cells was
      highly time dependent. The finding that some ITCs could inhibit the proliferation
      of cancer cells in a largely time-independent manner is significant because ITCs
      that enter the human body are rapidly cleared through urinary excretion. Using
      human promyelocytic leukemia HL60/S as model cells, and focusing on AITC and
      BITC, we found that these ITCs modulated multiple cellular targets involved in
      proliferation, including the disruption of mitochondrial membrane potential,
      activation of multiple caspases, arrest of cell cycle progression, and induction
      of differentiation. Again, only a 3-h incubation of the cells with the ITCs was
      enough to exert their full effect on these targets. Taken together, our findings
      suggest that selected ITCs can rapidly initiate growth inhibition of cancer cells
      by simultaneously modulating multiple cellular targets, and their
      antiproliferative activity may be largely unaffected by their metabolism and
      disposition in vivo.

PMID- 14578468
TI  - G3139 (oblimersen) may inhibit prostate cancer cell growth in a partially bis-CpG
      dependent non-antisense manner.
AB  - G3139 is an 18-mer phosphorothioate oligodeoxyribonucleotide, which is targeted
      to the initiation codon region of the bcl-2mRNA. Although treatment of PC3
      prostate cancer cells with G3139, which contains two CpG motifs, causes a
      dramatic decrease in bcl-2 protein expression after 3 days, it did not result in
      significant cellular apoptosis, as it does in many other cell lines. The absence
      of apoptosis was demonstrated by the absence of pro-caspase 3 cleavage products
      and of Annexin V cell surface expression. In addition, ATP production and the
      mitochondrial membrane potential DeltaPsim were preserved. Despite this, G3139
      significantly inhibited the rate of cellular proliferation in complete media and
      blocked cloning in soft agar. G4232, a variant of G3139 that down-regulates bcl-2
      expression to the same extent but has both CpG cytidines C5 methylated, was only
      minimally antiproliferative. A series of mismatched G3139-related oligomers were
      synthesized that could also substantially down-regulate bcl-2 protein expression,
      but only if the CpG motifs were preserved, demonstrating the presence of
      additional non-antisense mechanisms. G3139 caused production of reactive oxygen
      species in growth-arrested cells and oxidation of nuclear guanosine to 8-hydroxy
      2'-deoxyguanosine, as determined by 1F7 monoclonal antibody staining.
      Bromodeoxyuridine incorporation studies demonstrated that G3139 induced a G1-S
      entry block and an intra-S-phase block in PC3 cells that persisted as long as 3
      days. This finding coincides with the observation that expression of several
      proteins encoded by S-phase genes, including c-myb and poly(ADP-ribose)
      polymerase, were significantly reduced. These results illustrate the complexity
      of the mechanism of action of G3139 in PC3 cells.

PMID- 14578470
TI  - Cdc25A-inhibitory properties and antineoplastic activity of bisperoxovanadium
      analogues.
AB  - Bisperoxovanadium (bpV) compounds are irreversible protein tyrosine phosphatase
      (PTP) inhibitors with a spectrum of activity distinct from that of vanadium
      salts. We studied the efficacy of a panel of bpVs as antineoplastic agents in
      vitro and in vivo with a view to investigating phosphatases as potential
      antineoplastic targets. The Cdc25A dual-specificity phosphatase is an oncoprotein
      required for progression through G(1)-S. It cooperates with oncogenic Ras to
      transform cells and is overexpressed in several cancers. Cdc25A is therefore an
      attractive candidate phosphatase target for the antineoplastic activity of bpV
      compounds. Cytotoxicity was examined in 28 cancer cell lines and in vivo efficacy
      was examined in a DA3 murine mammary carcinoma model. In vitro phosphatase assays
      were used to directly measure phosphatase inhibition, comparing Cdc25A to
      hVH2/DSP4, leukocyte antigen related/receptor type PTPF catalytic domain (LAR),
      Yersinia pestis phosphatase (YOPH), and T-cell PTPase/non-receptor type PTP2
      (TCPTP). CDK2 activity and Rb phosphorylation were examined by immunocomplex
      kinase assays and Western blot. Cdc25A is at least 20-fold more sensitive to bpV
      inhibition than hVH2/DSP4, and 3- to 10- fold more sensitive than TCPTP and LAR.
      bpV inhibition of Cdc25A in cells leads to CDK2 inactivation and
      hypophosphorylation Rb, resulting in G1-S arrest and induction of p53-independent
      apoptosis. The most cytotoxic analogue, bpV[4,7-dimethyl-1,10-phenanthroline
      bisperoxo-oxo-vanadium (Me2Phen)], shows submicromolar IC50s against a panel of
      cell lines and inhibited tumor growth by 80% in mice. These results demonstrate
      that bpVs may have significant antineoplastic activity. In addition, they are in
      vitro and in vivo inhibitors of phosphatases including Cdc25A, suggesting that
      phosphatases may be appropriate targets for novel antineoplastic agents and that
      further development of these agents, targeting them to specific phosphatases such
      as CDC25A, may lead to novel agents with enhanced antineoplastic activity.

PMID- 14578471
TI  - Blockage of abasic site repair enhances antitumor efficacy of 1,3-bis-(2
      chloroethyl)-1-nitrosourea in colon tumor xenografts.
AB  - Methoxyamine (MX) has been shown to potentiate the antitumor effect of
      temozolomide (TMZ) in human tumor xenograft models. This potentiation is due to
      the reactivity of MX with apurinic/pyrimidinic (AP) sites in DNA, which are
      formed following DNA glycosylase removal of TMZ-induced methyl-purine adducts. MX
      bound AP sites cannot be further processed by base excision repair (BER),
      resulting in cell death. On the basis of this finding, we investigated in vivo
      whether MX enhanced therapeutic efficacy of other agents, such as 1,3-bis-(2
      chloroethyl)-1-nitrosourea (BCNU) that generates AP sites during DNA repair. Nude
      mice carrying human colon tumor xenografts, HCT116 and HCT116-Ch3, were treated
      by a single injection (i.p) of BCNU alone (30 mg/kg) or MX (2 mg/kg) combined
      with BCNU. The effect on tumor growth of BCNU alone was very moderate. Combined
      administration of MX and BCNU produced significant inhibition of tumor growth.
      Tumor growth delays were 14 +/- 3 days in HCT116 and 16 +/- 2 days in HCT116-Ch3
      tumors, respectively (P < 0.05 versus control or BCNU alone groups). Similar
      results were also observed in SW480 and DLD1 tumors. Importantly, no systemic
      toxicity was noted with BCNU and MX. In contrast, BCNU (at dose of 25 mg/kg)
      combined with O(6)-benzylguanine (BG), an inhibitor of O(6)-alkylguanine-DNA
      alkyltransferase (AGT) being tested in clinical trials, caused toxic death in all
      treated mice. However, a lower dose BCNU (10 mg/kg) combined with BG and MX had
      significant antitumor effect without toxic death. Thus, targeting BER with MX is
      a promising strategy to improve the antitumor activity of BCNU and perhaps other
      DNA-damaging agents.

PMID- 14578472
TI  - Inhibition of lysophosphatidic acid acyltransferase beta disrupts proliferative
      and survival signals in normal cells and induces apoptosis of tumor cells.
AB  - Lysophosphatidic acid acyltransferase beta (LPAAT-beta) is an intrinsic membrane
      protein that catalyzes the synthesis of phosphatidic acid (PA) from lysoPA. Given
      that PA is a cofactor in a number of signaling cascades that are constitutively
      active in tumors, we evaluated the role of PA produced by LPAAT-beta in Xenopus
      oocyte meiotic maturation assays and an isoform-specific inhibitor of LPAAT-beta
      in mammalian cell assays. We found that ectopic overexpression of LPAAT-beta
      cooperates in activation of the Ras/Raf/Erk pathway in Xenopus oocytes and that
      inhibition of LPAAT-beta inhibits signaling in both the Ras/Raf/Erk and PI3K/Akt
      pathways. When LPAAT-beta activity is suppressed by CT32228 (N-(4-bromo-phenyl)-6
      (5-chloro-2-methyl-phenyl)-[1,3,5]triazine-2,4-diamine), an isoform-specific
      noncompetitive inhibitor, tumor cells undergo mitotic catastrophe while most
      normal cells simply arrest or become quiescent. The data presented here suggest
      that PA produced by LPAAT-beta plays an important role in signaling pathways
      critical to tumor cell survival.

PMID- 14578473
TI  - New tools for cancer chemotherapy: computational assistance for tailoring
      treatments.
AB  - Computational models of cancer chemotherapy have the potential to streamline
      clinical trial design, contribute to the design of rational, tailored treatments,
      and facilitate our understanding of experimental results. Mechanistic models
      based on functional data from tumor biopsies will enable physicians to predict
      response to treatment for a specific patient, in contrast to statistical models
      in which the probability of response for a given patient may differ substantially
      from the population average. While microarray analyses of gene expression also
      show promise for guiding individualized treatments, it may be difficult to link
      statistical mining of microarray data with mechanistic, tailored treatments.
      Furthermore, gene expression does not identify how drugs should be scheduled.
      This review summarizes mechanistic mathematical models developed to improve the
      design of chemotherapy regimens. Mechanistic models that incorporate both genetic
      resistance and cell cycle-mediated resistance during treatment with multiple
      drugs will be most useful in designing treatment regimens tailored for
      individuals. Because there are already a number of papers that address the
      applications of microarray technology, we will limit our discussion to the
      contrasts between mechanistic computational models and microarray technology, and
      how these two approaches may complement one another.

PMID- 14578474
TI  - Modulation of the excitability of cholinergic basal forebrain neurones by KATP
      channels.
AB  - The expression of ATP-sensitive K(+) (K(ATP)) channels by magnocellular
      cholinergic basal forebrain (BF) neurones was investigated in thin brain slice
      and dissociated cell culture preparations using a combination of whole-cell,
      perforated-patch and single-channel recording techniques. Greater than 95% of BF
      neurones expressed functional K(ATP) channels whose activation resulted in
      membrane hyperpolarization and a profound fall in excitability. The whole-cell
      K(ATP) conductance was 14.0 +/- 1.5 nS and had a reversal potential of -91.4 +/-
      0.9 mV that shifted by 59.6 mV with a tenfold increase in [K(+)](o). I(KATP) was
      inhibited reversibly by tolbutamide (IC(50) of 34.1 microM) and irreversibly by
      glibenclamide (0.3-3 nM) and had a low affinity for [ATP](i) (67% reduction with
      6 mm[MgATP](i)). Using perforated-patch recording, a small proportion of the
      conductance was found to be tonically active. This was weakly potentiated by
      diazoxide (0.1 mm extracellular glucose) but insensitive to pinacidil (< or =500
      microM). Single-channel K(ATP) currents recorded in symmetrical 140 mm K(+)
      containing solutions exhibited weak inward rectification with a mean conductance
      of 66.2 +/- 1.9 pS. Channel activity was inhibited by MgATP (>50 microM) and
      activated by MgADP (200 microM). The K(+) channels opener diazoxide (200-500
      microM) increased channel opening probability (NP(o)) by 486 +/- 120% whereas
      pinacidil (500 microM) had no effect. In conclusion, the characteristics of the
      K(ATP) channels expressed by BF neurones are very similar to channels composed of
      SUR1 and Kir6.2 subunits. In the native cell, their affinity for ATP is close to
      the resting [ATP](i), potentially allowing them to be modulated by
      physiologically relevant changes in [ATP](i). The effect of these channels on the
      level of ascending cholinergic excitation of the cortex and hippocampus is
      discussed.

PMID- 14578476
TI  - Recovering from eccentric exercise: get weak to become strong.

PMID- 14578477
TI  - Cortisol enhances structural maturation of the hypoplastic fetal lung in sheep.
AB  - Although exogenous corticosteroids advance structural maturation of the fetal
      lung, they can adversely affect fetal lung and body growth. Our aim was to
      determine whether cortisol, at physiological doses, can enhance structural
      maturation of the hypoplastic fetal lung without affecting fetal lung growth.
      Fetal sheep were divided into four groups (n= 5 for each) and lung hypoplasia
      (LH) was induced in two groups. Increasing doses of cortisol (1.5-4.0 mg) were
      infused into one group of fetuses with LH and one group without LH; the other two
      groups received saline. LH retarded structural development, reduced tropoelastin
      mRNA levels, reduced hydroxyproline and elastin contents, and increased active
      matrix metalloproteinase-2 (MMP-2) levels in the fetal lung. Cortisol infusions
      had no effect on fetal lung growth or body weights. In fetuses with LH, cortisol
      increased the percentage airspace, reduced the interalveolar wall thickness,
      increased alveolar number and reduced the increase in active MMP-2 levels. Thus,
      relatively low doses of cortisol can enhance structural maturation of the fetal
      lung without adversely affecting fetal lung growth. However, cortisol did not
      correct the abnormal deposition of elastin within the alveolar parenchyma
      associated with LH, indicating that secondary septal crest formation remained
      abnormal.

PMID- 14578475
TI  - Electrophysiological properties of human mesenchymal stem cells.
AB  - Human mesenchymal stem cells (hMSC) have gained considerable interest due to
      their potential use for cell replacement therapy and tissue engineering. One
      strategy is to differentiate these bone marrow stem cells in vitro into
      cardiomyocytes prior to implantation. In this context ion channels can be
      important functional markers of cardiac differentiation. At present there is
      little information about the electrophysiological behaviour of the
      undifferentiated hMSC. We therefore investigated mRNA expression of 26 ion
      channel subunits using semiquantitative RT-PCR and recorded transmembrane ion
      currents with the whole-cell voltage clamp technique. Bone marrow hMSC were
      obtained from healthy donors. The cells revealed a distinct pattern of ion
      channel mRNA with high expression levels for some channel subunits (e.g. Kv4.2,
      Kv4.3, MaxiK, HCN2, and alpha1C of the L-type calcium channel). Outward currents
      were recorded in almost all cells. The most abundant outward current rapidly
      activated at potentials positive to +20 mV. This current was identified as a
      large-conductance voltage- and Ca(2+)-activated K(+) current, conducted by MaxiK
      channels, due to its high sensitivity to tetraethylammonium (IC(50)= 340 microm)
      and its inhibition by 100 nm iberiotoxin. A large fraction of cells also
      demonstrated a more slowly activating current at potentials positive to -30 mV.
      This current was selectively inhibited by clofilium (IC(50)= 0.8 microm). Ba(2+)
      inward currents, stimulated by 1 microm BayK 8644 were found in a few cells,
      indicating the expression of functional L-type Ca(2+) channels. Other inward
      currents such as sodium currents or inward rectifier currents were absent. We
      conclude that undifferentiated hMSC express a distinct pattern of ion channel
      mRNA and functional ion channels that might contribute to physiological cell
      function.

PMID- 14578479
TI  - Structural changes in loaded equine tendons can be monitored by a novel
      spectroscopic technique.
AB  - This study aimed to investigate the preferential collagen fibril alignment in
      unloaded and loaded tendons using elastic scattering spectroscopy. The device
      consisted of an optical probe, a pulsed light source (320-860 nm), a spectrometer
      and a PC. Two probes with either 2.75 mm or 300 microm source-detector
      separations were used to monitor deep and superficial layers, respectively.
      Equine superficial digital flexor tendons were subjected to ex vivo progressive
      tensional loading. Seven times more backscattered light was detected parallel
      rather than perpendicular to the tendon axis with the 2.75 mm separation probe in
      unloaded tendons. In contrast, using the 300 microm separation probe the plane of
      maximum backscatter (3-fold greater) was perpendicular to the tendon axis. There
      was no optical anisotropy in the cross-sectional plane of the tendon (i.e. the
      transversely cut tendon surface), with no structural anisotropy. During
      mechanical loading (9-14% strain) backscatter anisotropy increased 8.5- to 18.5
      fold along the principal strain axis for 2.75 mm probe separation, but almost
      disappeared in the perpendicular plane (measured using the 300 microm probe
      separation). Optical (anisotropy) and mechanical (strain) measurements were
      highly correlated. We conclude that spatial anisotropy of backscattered light can
      be used for quantitative monitoring of collagen fibril alignment and tissue
      reorganization during loading, with the potential for minimally invasive real
      time structural monitoring of fibrous tissues in normal, pathological or
      repairing tissues and in tissue engineering.

PMID- 14578481
TI  - Evidence for the involvement of VPAC1 and VPAC2 receptors in pressure-induced
      vasodilatation in rodents.
AB  - A transient increase in skin blood flow in response to an innocuous local
      pressure application, defined as pressure-induced vasodilatation (PIV), delays
      the occurrence of ischaemia, suggesting a protective feature against applied
      pressure. The PIV response depends on capsaicin-sensitive nerve fibres and
      calcitonin gene-related peptide (CGRP) has been shown to be involved. In these
      fibres, CGRP coexists with pituitary adenylate cyclase-activating polypeptide
      (PACAP). Three distinct receptors mediate the biological effects of PACAP: VPAC1
      and VPAC2 receptors binding with the same affinity for PACAP and vasoactive
      intestinal peptide and PAC1 receptors showing high selectivity for PACAP. Because
      the receptors are widely expressed in the nervous system and in the skin, we
      hypothesized that at least one of them is involved in PIV development. To verify
      this hypothesis, we used [D-p-Cl-Phe(6),Leu(17)]-VIP (nonspecific antagonist of
      VPAC1/VPAC2 receptors), PG 97-269 (antagonist of VPAC1 receptors), PACAP(6-38)
      (antagonist of VPAC2/PAC1 receptors) and Max.d.4 (antagonist of PAC1 receptors)
      in anaesthetized rodents. The blockade of VPAC1/VPAC2, VPAC1 or VPAC2/PAC1
      receptors eliminated the PIV response, whereas PAC1 blockade had no effect,
      demonstrating an involvement of VPAC1/VPAC2 receptors in PIV development.
      Moreover, endothelium-independent and -dependent vasodilator responses were
      unchanged by the VPAC1/VPAC2 antagonist. Thus, the absence of a PIV response
      following VPAC1/VPAC2 blockade cannot be explained by any dysfunction of the
      vascular smooth muscle or endothelial vasodilator capacity. The involvement of
      VPAC1/VPAC2 receptors in the development of PIV seems to imply a series
      relationship in which each receptor type (CGRP, VPAC1, VPAC2) is necessary for
      the full transmission of the response.

PMID- 14578482
TI  - Intersitial exluded volumes: the effect of charge.

PMID- 14578483
TI  - Thermogenesis elicited by skin cooling in anaesthetized rats: lack of
      contribution of the cerebral cortex.
AB  - Non-noxious cooling stimuli were delivered to the shaved back of urethane
      chloralose-anaesthetized, artificially ventilated rats using a plastic bag
      containing water at 24-40 degrees C. Cooling of the skin by 2-6 degrees C
      increased the rate of whole body oxygen consumption (.V(O(2)) and triggered
      electromyographic (EMG) activity recorded from the neck or femoral muscles. The
      cooling-induced (.V(O(2)) responses did not depend on core (colonic) temperature
      and followed skin temperature in a graded manner. Pretreatment with the beta
      blocker propranolol (10 mg kg(-1), i.v.) greatly attenuated the (.V(O(2))
      response but did not affect the EMG response. On the other hand, pretreatment
      with the muscle relaxant pancuronium bromide (2 mg kg(-1), i.v.) affected the
      (.V(O(2)) response very slightly but completely abolished the EMG activity.
      Accordingly, the cooling stimulus activated mainly non-shivering thermogenesis.
      Next, the contribution of the cerebral cortex to the cooling-induced
      thermogenesis was examined. Power spectral analysis of the electroencephalogram
      (EEG) showed that the cooling stimulus largely inhibited delta (0.5-3 Hz) waves,
      enhanced theta (3-8 Hz) waves, and slightly increased frequencies higher than 8
      Hz. Pinching the hindpaw elicited changes in EEG similar to those elicited by
      skin cooling but did not increase the (.V(O(2)). Therefore, there was no
      relationship between changes in the EEG and the magnitude of thermogenesis.
      Finally, skin cooling increased the (.V(O(2)) of decorticated rats but did not
      increase that of decerebrated rats. The results suggest that the subcortical
      forebrain structure, but not cortical activation, is indispensable for non
      shivering thermogenesis elicited by cooling stimulation of the skin.

PMID- 14578484
TI  - Ganglion cell contributions to the rat full-field electroretinogram.
AB  - The purpose of this study was to determine what contributions are made to the rat
      full-field electroretinogram (ERG) by ganglion cells (GCs). To that end, the ERG
      was assessed longitudinally following optic nerve transection (ONTx). Additional
      studies were conducted using intravitreal injections of pharmacologically active
      substances. The ERG was recorded simultaneously from both eyes of anaesthetized
      adult Brown-Norway rats (ketamine: xylazine: acepromazine, 55: 5: 1 mg kg(-1))
      using custom silver chloride electrodes. Stimuli were brief, white xenon
      discharges delivered via a Ganzfeld under dark-adapted and light-adapted
      conditions (150 cd m(-2)). ERGs were obtained 1, 2, 3, 4 and 9 weeks after ONTx
      (n = 8) or sham (n = 8) operations. ONTx reduced both positive and negative
      components of the scotopic threshold response (pSTR and nSTR). Scotopic ERG
      responses to brighter flashes, including a-waves, b-waves and oscillatory
      potentials (OPs) were unaffected by ONTx. ONTx reduced the photopic b-wave and
      OPs. TTX (6 microM) reduced the pSTR and nSTR, but not the scotopic a-wave, b
      wave or OPs. TTX had dramatic effects on the photopic ERG, surpassing the effects
      of ONTx. TTX application 9 weeks post-ONTx had little additional effect on the
      STR. Inhibition of inner retinal responses using GABA (10 mM) or NMDA (0.8 mM)
      reduced the nSTR substantially. Similar results were obtained with antagonists of
      AMPA/KA ionotropic glutamate receptors 6-cyano-7-nitroquinoxaline-2,3(1H,4H)
      dione (CNQX, 0.2 mM) or cis-2,3-piperidinedicarboxylic acid (PDA, 5 mm); however,
      both also reduced the scotopic b-wave by approximately 40 %. By contrast, the
      NMDA receptor antagonist D(-)-2-amino-7-phosphonoheptanoic acid (D-AP7, 0.2 mM)
      had no effect alone, but the combination of D-AP7 and CNQX completely abolished
      the STR. The results of this study indicate that: (1) both pSTR and nSTR
      components in the rat depend directly upon intact GC responses, and that amacrine
      cell contributions to these components are relatively small; (2) scotopic ERG
      response components to brighter flashes receive little influence from GCs; (3)
      the rat photopic ERG also reflects GC signals and may serve as an additional
      useful test of GC function; (4) TTX had dramatic effects on the rat photopic ERG
      that were not attributable to GC currents, but rather to voltage-gated sodium
      currents in amacrine or interplexiform cells; (5) a small residual negative STR
      persisted after ONTx that was likely to be generated by graded responses of third
      order retinal cells, most likely amacrine cells.

PMID- 14578485
TI  - Glycine rectifies vascular dysfunction induced by dietary protein imbalance
      during pregnancy.
AB  - Protein restriction in rat pregnancy programmes the development of elevated
      systolic blood pressure and vascular dysfunction in the offspring. A recent study
      has shown that hypertension is reversed by maternal glycine supplementation.
      Whether this protective effect is exerted directly on the embryo and fetus, or
      indirectly via effects on the mother, is unknown although we have previously
      shown abnormalities in the maternal vasculature. We tested the hypothesis that
      dietary glycine repletion would reverse endothelial dysfunction in protein
      restricted pregnant rat dams using wire myography. Impaired acetylcholine- (P <
      0.01) and isoprenaline-induced (P < 0.05) vasodilatation in isolated mesenteric
      arteries (MA) from protein-restricted pregnant dams was accompanied by reduced
      vascular nitric oxide (NO) release (P < 0.05). Dietary glycine supplementation
      reversed vascular dysfunction in MA (P < 0.05) and improved NO release thus
      potentially protecting the maternal circulation. The impaired NO release in the
      MA of low protein diet dams was not accompanied by reduced eNOS mRNA expression,
      suggesting that eNOS activity was altered. Protein restriction did not alter the
      vascular function of a conduit artery, the thoracic aorta. These results provide
      evidence that adequate provision of glycine, a conditionally essential amino acid
      in pregnancy, may play a role in the vascular adaptations to pregnancy,
      protecting the fetus from abnormal programming of the cardiovascular system.

PMID- 14578490
TI  - Phosphoarginine regulation of the squid nerve Na+/Ca2+ exchanger: metabolic
      pathway and exchanger-ligand interactions different from those seen with ATP.
AB  - In squid nerves the Na(+)-Ca(2+) exchanger is up-regulated by ATP and
      phosphoarginine (PA). ATP regulation involves drastic alterations in the
      Na(+)(i), H(+)(i) and Ca(2+)(i) interactions with the large intracellular
      cytoplasmic loop of the exchanger protein. In this work we explored the
      mechanisms associated with PA regulation in intracellular dialysed squid axons
      and squid optic nerve membrane vesicles. Dialysed axons were used to measure the
      four modes of exchange fluxes (Na(+)(o)-Ca(2+)(i) or forward exchange, Ca(2+)(o)
      Na(+)(i) or reverse exchange, Ca(2+)(o)-Ca(2+)(i) exchange and Na(+)(o)-Na(+)(i)
      exchange) under controlled intra- and extracellular conditions. Inside-out
      membrane vesicles allowed measurement of the Na(+)-gradient-dependent (45)Ca(2+)
      uptake (forward mode) as influenced by ligands and digestion with chymotrypsin
      from the intracellular side. The results show that, unlike ATP, PA regulation
      does not affect the H(+)(i), Na(+)(i) and Ca(2+)(i) interactions with the
      intracellular 'regulatory' loop, but increases the affinity of the intracellular
      transport sites, preferentially for Ca(2+)(i) (about 20-fold) over Na(+)(i)
      (50%); i.e. PA favours the forward mode over the other exchange modes.
      Intracellular chymotrypsin digestion removed ATP regulation while leaving
      modulation by PA unmodified. Western blot analysis suggested that chymotrypsin
      disrupts the large intracellular loop. Together these results indicate that ATP
      and PA regulations are associated with different structures inside and outside
      the exchanger protein. Based on these observations we expanded our previous model
      for metabolic regulation of the Na(+)-Ca(2+) exchanger by adding to the original
      'ATP region' a new zone, the 'PA region', related to the intracellular transport
      sites for Na(+)(i) and Ca(2+)(i). This new model is able to explain most previous
      and present results.

PMID- 14578486
TI  - Modulation of afterpotentials and firing pattern in guinea pig CA3 neurones by
      group I metabotropic glutamate receptors.
AB  - Activation of group I metabotropic glutamate receptors (mGluRs) alters the firing
      patterns of individual CA3 pyramidal cells in guinea pig hippocampal slices.
      Following addition of the selective group I agonist (S)-3,5
      dihydroxyphenylglycine (DHPG) to the bathing solution, pyramidal cells initially
      firing regular, single action potentials switched to firing in brief bursts. This
      change in firing pattern resulted from modulation by mGluRs of three
      afterpotentials. The medium and slow afterhyperpolarizations (m and sAHPs) were
      blocked by mGluR activation. In addition, a voltage-dependent after
      depolarization (ADP) was induced. Recordings from mutant mice lacking
      phospholipase C(beta1) (PLC(beta1)) showed that mGluR block of the mAHP, as well
      as induction of the ADP, depended on the phosphoinositide hydrolysis pathway.
      Block of the sAHP, however, was partly spared in the absence of PLC(beta1).
      Optical recordings of post spike intracellular Ca(2+) rises showed that mGluR
      block of the AHP was not mediated by alterations of action potential-associated
      Ca(2+) increases (Ca(2+) transients). The mGluR induction of an ADP was also
      independent of any changes in the Ca(2+) transient. The mGluR-induced change in
      the firing pattern of hippocampal pyramidal cells is thus the result of multiple
      mechanisms, including suppression of both m and sAHPs and activation of an ADP,
      that act together to produce a specific excitatory effect, namely an increased
      likelihood that a single action potential will lead immediately to one or more
      following action potentials.

PMID- 14578492
TI  - Enhancement of microvessel tortuosity in the vastus lateralis muscle of old men
      in response to endurance training.
AB  - Muscle microvascularization is usually quantified in transverse sections, in
      absolute terms (capillaries around fibres, CAF, or capillary-to-fibre ratio, C/F)
      or as CAF related to fibre area (CAF/area, CAFA). The capillary-to-fibre
      perimeter exchange ratio (CFPE) has been introduced in order to assess the role
      of the capillary-to-fibre interface in resistance to O(2) diffusion. The ratio
      between the length of capillaries in contact with fibres and fibre perimeter
      (LC/PF) has also been used as an index for capillary tortuosity. The possibility
      of change in capillary tortuosity with endurance training was not considered in
      previous studies. Consequently, this study investigated the effect of 14 weeks of
      endurance training on muscle microvascularization, including microvessel
      tortuosity, in 11 elderly men (8th decade). Microvessels were analysed using the
      CD31 antibody. Together with the significant increase in peak oxygen exchange and
      citrate synthase activity, there was a significant increase in C/F. While CFPE
      and CAFA remained unchanged, an important finding was the clear increase in LC/PF
      (56%; P < 0.001) for a same sarcomere length. We also found a strong correlation
      between oxidative enzyme activity and LC/PF both before and after training. These
      results indicate that endurance training induces significant remodelling in the
      microvessel network in elderly men and that an increase in the degree of
      microvessel tortuosity would be an important mechanism of adaptation to endurance
      training.

PMID- 14578493
TI  - Restorative dentistry and research: a contradiction?

PMID- 14578494
TI  - Construct and predictive validity of clinical caries diagnostic criteria
      assessing lesion activity.

PMID- 14578495
TI  - Coagulation derangements in oral and maxillofacial surgery in patients with a
      documented cancer: a follow-up study after surgery.

PMID- 14578496
TI  - Fascination with epithelia: architecture, proteins, and functions.

PMID- 14578497
TI  - Proteome analysis of oral pathogens.
AB  - The oral environment contains diverse communities of micro-organisms including
      bacteria, fungi, protozoa, and viruses. Studies of oral ecology have led to an
      appreciation of the complexity of the interactions that oral micro-organisms have
      with the host in both health and disease. Despite this, diseases such as dental
      caries and periodontal diseases are still worldwide human ailments, resulting in
      a high level of morbidity and an economic burden to society. Proteomics offers a
      new approach to the understanding of holistic changes occurring as oral micro
      organisms adapt to environmental change within their habitats in the mouth.

PMID- 14578498
TI  - Intracellular calcium in signaling human beta-defensin-2 expression in oral
      epithelial cells.
AB  - Expression of human beta-defensins is correlated with differentiation in the oral
      epithelium, consistent with their function as part of the epithelial
      antimicrobial barrier. Because calcium is a known regulator of epithelial
      differentiation, we tested the hypothesis that calcium concentration mediates
      beta-defensin expression. Gingival epithelial cells were cultured in medium
      containing low calcium concentration (0.03 mM), then either changed to high
      extracellular calcium concentrations or stimulated with thapsigargin to release
      intracellular calcium stores in the presence or absence of BAPTA-AM, a calcium
      chelator. Human beta-defensin-2 (hBD-2) mRNA expression was rapidly induced by
      thapsigargin, and more slowly induced by high extracellular calcium. Induction of
      hBD-2 peptide was confirmed by immunofluorescence. BAPTA-AM inhibited hBD-2
      induction by both thapsigargin and calcium in a dose-dependent fashion. In
      addition, BAPTA-AM inhibited hBD-2 induction by a bacterial stimulant.
      Collectively, these findings demonstrate that intracellular calcium is a critical
      mediator of hBD-2 expression. Abbreviations used in this study are: BAPTA-AM, 1,2
      bis(2-aminophenoxy)-ethane-N,N,N',N'-tetra-acetic acid tetrakis (acetoxymethyl
      ester); DMSO, dimethylsulfoxide; F. nucleatum, Fusobacterium nucleatum; GAPDH,
      glyceraldehyde-3-phosphate dehydrogenase; HBDs, human beta-defensins; HGECs,
      human gingival epithelial cells; MAP, mitogen-activated protein; and RT-PCR,
      reverse-transcriptase/polymerase chain-reaction.

PMID- 14578499
TI  - Pro-inflammatory cytokines up-regulate MUC1 gene expression in oral epithelial
      cells.
AB  - The membrane-bound mucin MUC1 is expressed ubiquitously on epithelial surfaces
      and is thought to provide protection from bacterial and chemical injury. The
      present study was undertaken to determine whether MUC1 was expressed in cultured
      oral epithelial cells and whether expression is modulated by pro-inflammatory
      mediators released as part of the host response to infection by oral pathogens.
      Northern and Western blotting experiments showed that KB cells express MUC1 mRNA
      and protein. When cells were treated with interleukins (IL-1beta, IL-6), tumor
      necrosis factor-alpha (TNF-alpha), or interferon-gamma (IFN-gamma), or
      combinations of these, real-time PCR demonstrated that MUC1 mRNA increased 1.4-
      to 3.2-fold. Interestingly, a significant increase in levels of MUC1 protein was
      also observed. While no effect was observed when KB cells were incubated with LPS
      from Porphyromonas gingivalis, infection of KB monolayers with this oral pathogen
      caused a 2.85-fold increase in MUC1 transcript levels. These results suggest that
      increased MUC1 synthesis may be a key element in the host response to infection
      with oral pathogens.

PMID- 14578500
TI  - Involvement of CD73 (ecto-5'-nucleotidase) in adenosine generation by human
      gingival fibroblasts.
AB  - Adenosine has various biological effects on human gingival fibroblasts (HGF) and
      epithelial cells closely associated with inflammation, such as cytokine
      production and cell adhesion. However, the mechanism of adenosine formation in
      periodontal tissues is not yet defined. In this study, we examined the
      involvement of CD73 (ecto-5'-nucleotidase) in adenosine generation by HGF. CD73
      was detected on in vitro-maintained HGF by immunocytochemistry and flow
      cytometric analysis. Adenosine production was observed following the addition of
      5'-AMP, the substrate of CD73-associated ecto-5'-nucleotidase. Moreover, the
      addition of 5'-AMP to cultured HGF resulted in the elevation of cyclic adenosine
      monophosphate (cAMP). The 5'-AMP-induced increase in intracellular cAMP level was
      inhibited markedly by xanthine amine congener, an adenosine receptor antagonist,
      and partially by alpha,beta-methylene adenosine 5'-diphosphate, an ecto-5'
      nucleotidase inhibitor. These results suggest that CD73 on HGF is a critical
      enzyme responsible for the generation of adenosine, an immunomodulator that
      activates adenosine receptors.

PMID- 14578501
TI  - Induction of CD13 on T-lymphocytes by adhesive interaction with gingival
      fibroblasts.
AB  - Lymphocytes in peripheral blood do not express CD13 (aminopeptidase N), a
      membrane alanyl metallopeptidase. However, it has been demonstrated that locally
      infiltrated lymphocytes in chronic inflammatory sites can be CD13-positive, and
      possible involvement of stromal cell adherence in the induction of CD13 has been
      suggested. In this study, we examined whether T-lymphocyte/gingival-fibroblast
      interaction can activate T-lymphocytes to express CD13. CD13 expression was
      induced on PMA-activated T-lymphocytes only when they adhered directly to human
      gingival fibroblasts (HGF) at 2 hrs after the co-culture began, while an increase
      in the enzyme activity of CD13 was also confirmed in activated T-lymphocytes that
      had been co-cultured with HGF. Furthermore, CD13-positive T-lymphocytes were
      detected in inflamed gingival tissues in vivo. Analysis of these results
      indicates that direct interaction with HGF is essential for the induction of CD13
      expression on T-lymphocytes that was also observed in periodontitis lesions.

PMID- 14578502
TI  - Blood flow and interstitial fluid pressure in the rat submandibular gland during
      changes in perfusion.
AB  - The submandibular gland is a cell-rich encapsulated organ with high transport of
      fluid through the interstitial space during salivation. We hypothesized that the
      gland is a low-compliant tissue, i.e., that a modest increase in fluid volume
      will produce a rise in interstitial fluid pressure (IFP) counteracting fluid
      filtration into the interstitium. To test this hypothesis, we measured IFP with
      micropipettes and glandular blood flow (GBF) with a laser-Doppler flowmeter
      during changes in perfusion. Clamping of the carotid artery or the jugular vein,
      or electrical stimulation of the sympathetic or parasympathetic nerve to the
      gland, induced changes in perfusion. Baseline IFP averaged 3.5 +/- 0.5 mm Hg.
      Clamping of the artery reduced IFP and GBF (-56.5 +/- 8.4% and -53.1 +/- 6.4%,
      respectively), whereas clamping of the vein decreased GBF (-21.6 +/- 14.3%) and
      increased IFP (141.2 +/- 27.4%). Sympathetic nerve stimulation reduced both
      parameters (-86.9 +/- 16.5% and -74.4 +/- 7.0%, respectively). In contrast,
      stimulation of the parasympathetic nerve elicited an increase in GBF (133.2 +/-
      5.9%) and in IFP (173.3 +/- 41.4%). Thus, changes in vascular volume led to
      concomitant changes in IFP consistent with low tissue compliance, a phenomenon of
      importance for fluid volume regulation.

PMID- 14578503
TI  - Regulating bone formation via controlled scaffold degradation.
AB  - It is widely assumed that coupling the degradation rate of polymers used as cell
      transplantation carriers to the growth rate of the developing tissue will improve
      its quantity or quality. To test this hypothesis, we developed alginate hydrogels
      with a range of degradation rates by gamma-irradiating high-molecular-weight
      alginate to yield polymers of various molecular weights and structures.
      Decreasing the size of the polymer chains increased the degradation rate in vivo,
      as measured by implant retrieval rates, masses, and elastic moduli. Rapidly and
      slowly degrading alginates, covalently modified with RGD-containing peptides to
      control cell behavior, were then used to investigate the effect of biodegradation
      rate on bone tissue development in vivo. The more rapidly degrading gels led to
      dramatic increases in the extent and quality of bone formation. These results
      indicate that biomaterial degradability is a critical design criterion for
      achieving optimal tissue regeneration with cell transplantation.

PMID- 14578504
TI  - How does fluoride concentration in the tooth affect apatite crystal size?
AB  - Despite fluoride's (F) well-documented ability to prevent caries, the effects of
      F concentrations on enamel and dentin apatite crystals are unknown. The present
      study examined the hypothesis that tooth F concentration and tooth crystallite
      size correlate. One hundred human unerupted third molars were studied-53 from
      Fortaleza-Brazil (F water 0.7 ppm), 23 from Toronto (1.0 ppm), and 24 from
      Montreal (0.2 ppm). F concentration was analyzed by Neutron Activation Analysis
      and apatite crystal size by powder x-ray diffraction. A positive correlation
      between dentin F concentration and enamel crystallite length and width was found.
      Enamel crystallite length was significantly greater in teeth from Fortaleza than
      in teeth from Toronto (p = 0.011) and Montreal (p = 0.003). Enamel crystallite
      widths were significantly greater in Fortaleza teeth compared with those from
      Toronto (p = 0.020) and Montreal (p < 0.001). No difference in the dentin
      crystallite size was seen in the 3 regions. Thus, tooth F concentration and
      crystallite size correlate.

PMID- 14578505
TI  - Incorporation of casein phosphopeptide-amorphous calcium phosphate into a glass
      ionomer cement.
AB  - Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) nanocomplexes have
      been shown to prevent demineralization and promote remineralization of enamel
      subsurface lesions in animal and in situ caries models. The aim of this study was
      to determine the effect of incorporating CPP-ACP into a self-cured glass-ionomer
      cement (GIC). Incorporation of 1.56% w/w CPP-ACP into the GIC significantly
      increased microtensile bond strength (33%) and compressive strength (23%) and
      significantly enhanced the release of calcium, phosphate, and fluoride ions at
      neutral and acidic pH. MALDI mass spectrometry also showed casein phosphopeptides
      from the CPP-ACP nanocomplexes to be released. The release of CPP-ACP and
      fluoride from the CPP-ACP-containing GIC was associated with enhanced protection
      of the adjacent dentin during acid challenge in vitro.

PMID- 14578506
TI  - Anti-cardiolipin antibodies in sera from patients with periodontitis.
AB  - Antiphospholipid antibodies are commonly found in patients with systemic lupus
      erythematosus or the antiphospholipid syndrome, and a subset of such antibodies
      is associated with prothrombotic events such as stroke and with adverse pregnancy
      outcomes and fetal loss. We examined sera from 411 patients who were clinically
      characterized as to their periodontal disease status for serum levels of beta2
      glycoprotein I-dependent anti-cardiolipin autoantibodies (anti-CL). The
      prevalence of patients with chronic periodontitis (CP) and generalized aggressive
      periodontitis (GAgP) positive for anti-CL (16.2% and 19.3%, respectively) was
      greater than that in healthy controls (NP) and localized aggressive periodontitis
      (LAgP) patients (6.8% and 3.2%). Patients with these autoantibodies demonstrated
      increased pocket depth and attachment loss compared with patients lacking the
      antibodies. Analysis of the data indicates that patients with generalized
      periodontitis have elevated levels of autoantibodies reactive with phospholipids.
      These antibodies could be involved in elevated risk for stroke, atherosclerosis,
      or pre-term birth in periodontitis patients.

PMID- 14578509
TI  - How the atomic force microscope works.

PMID- 14578508
TI  - The role of auditory cues in modulating the perception of electric toothbrushes.
AB  - Recent research shows that what people hear can influence what they feel. We
      investigated whether the perception of an electric toothbrush might also be
      affected by the sound that it makes. Participants were required to make
      stereotypical brushing movements with a standard electric toothbrush while they
      rated either the pleasantness or the roughness of the vibrotactile stimulation
      they felt on their teeth. The results demonstrate that the perception of the
      sensations experienced during toothbrush use were systematically altered by
      variations in the auditory feedback elicited by the brushing action. Participants
      reported that the toothbrush felt more pleasant and less rough when either the
      overall sound level was reduced, or when just the high-frequency sounds were
      attenuated. These results highlight the significant role that auditory cues can
      play in modulating the perception and evaluation of everyday products in use, and
      provide a paradigm for future study in this area.

PMID- 14578507
TI  - Survivin, a potential early predictor of tumor progression in the oral mucosa.
AB  - Survivin is a recently described apoptosis inhibitor selectively over-expressed
      in most tumors. Immunohistochemistry was used to investigate a potential role of
      survivin as an early predictor of malignant transformation in precancerous and
      cancerous lesions of the oral cavity. Survivin was present in 10/30 cases (33%)
      of oral precancerous lesions without malignant progression, and in 15/16 cases
      (94%) of oral precancerous lesions evolved into full-blown squamous cell
      carcinoma. Tumors that progressed from these precancerous lesions retained
      widespread survivin positivity (100%). Variations among group means were highly
      statistically significant (p < 0.001). No significant correlation was found
      between survivin expression and the degree of dysplasia. High expression of
      cytoplasmic/nuclear survivin is an early event during oral carcinogenesis and may
      provide a useful tool for the identification of precancerous lesions at higher
      risk of progression into invasive carcinoma.

PMID- 14578510
TI  - Imaging methods in atomic force microscopy.

PMID- 14578511
TI  - Recognizing and avoiding artifacts in AFM imaging.

PMID- 14578512
TI  - Advanced biosensing using micromechanical cantilever arrays.

PMID- 14578513
TI  - Analysis of human fibroblasts by atomic force microscopy.

PMID- 14578514
TI  - Corneal tissue observed by atomic force microscopy.

PMID- 14578515
TI  - AFM study of surface structure changes in mouse spermatozoa associated with
      maturation.

PMID- 14578516
TI  - Calculation of cuticle step heights from AFM images of outer surfaces of human
      hair.

PMID- 14578517
TI  - Imaging living chondrocyte surface structures with AFM contact mode.

PMID- 14578518
TI  - Growth cones of living neurons probed by atomic force microscopy.

PMID- 14578519
TI  - Evaluating demineralization and mechanical properties of human dentin with AFM.

PMID- 14578520
TI  - Applying atomic force microscopy to studies in cardiac physiology.

PMID- 14578521
TI  - Imaging bacterial shape, surface, and appendages before and after treatments with
      antibiotics.

PMID- 14578522
TI  - Visualizing nuclear structure in situ by atomic force microscopy.

PMID- 14578523
TI  - Imaging surface and submembranous structures in living cells with the atomic
      force microscope: notes and tricks.

PMID- 14578524
TI  - Atomic force microscopy of protein complexes.

PMID- 14578525
TI  - Atomic force microscopy of interfacial monomolecular films of pulmonary
      surfactant.

PMID- 14578526
TI  - High-resolution analysis of the 3D organization of human metaphase chromosomes.

PMID- 14578527
TI  - Shape and volume of living aldosterone-sensitive cells imaged with the atomic
      force microscope.

PMID- 14578528
TI  - Localization of epithelial sodium channels by atomic force microscopy.

PMID- 14578529
TI  - High-resolution imaging of bacteriorhodopsin by atomic force microscopy.

PMID- 14578530
TI  - Measurement of mechanical properties of intact endothelial cells in fresh
      arteries.

PMID- 14578531
TI  - Observation of oxidative stress on yeast cells.

PMID- 14578532
TI  - Lymphoblastoid cells exposed to low-frequency magnetic fields: study by atomic
      force microscopy.

PMID- 14578533
TI  - Sample preparation method for observing RNA polymerase activity by atomic force
      microscopy.

PMID- 14578535
TI  - How to build up biosensors with the cantilever of the atomic force microscope.

PMID- 14578534
TI  - Atomic force microscopy of beta-amyloid: static and dynamic studies of
      nanostructure and its formation.

PMID- 14578536
TI  - Measurement of single molecular interactions by dynamic force microscopy.

PMID- 14578538
TI  - Assisted living and use of health services among medicaid beneficiaries with
      schizophrenia.
AB  - BACKGROUND: Considerable attention has been given to the appropriateness of
      mental and medical health care provided to residents of certain assisted living
      facilities specialized for the severely mentally ill. However, there exists
      little objective evidence regarding the level of services provided by these
      facilities in general. AIMS OF THE STUDY: To compare the use of mental and
      medical health services among persons with schizophrenia who were residing in
      assisted living facilities compared to those received by patients living
      independently and those who were homeless. METHODS: Medicaid claims were combined
      with person level data on living situation and psychological and social
      functioning for 1998-2000. Regression models were used to analyze whether living
      in a board-and-care facility was related to use of outpatient mental health
      services including case management, therapy, crisis stabilization, medication
      supervision, day treatment, and drug treatment, the probability of acute
      psychiatric hospitalization, the probability of hospitalization for physical
      health, and costs. RESULTS: Residents of board-and-care facilities had greater
      use of outpatient mental health services and lower rates of psychiatric and
      medical hospitalization. Pharmacy costs and total health care costs were highest
      in assisted living. DISCUSSION: Our data was observational, and selection
      processes related to illness severity likely affect living arrangement. Our
      analysis suggests that assisted living was related to greater use of outpatient
      mental health services and lower rates of hospitalization. IMPLICATIONS FOR
      HEALTH POLICIES: Assisted living facilities may provide a suitable environment
      though which to provide outpatient mental health services. Policy makers
      interested in reducing homelessness through interventions might consider
      subsidizing these facilities. IMPLICATIONS FOR FURTHER RESEARCH: Research studies
      should be designed to evaluate characteristics of assisted living facilities that
      lead to improved function and outcomes among residents.

PMID- 14578539
TI  - Antipsychotic medication use patterns and associated costs of care for
      individuals with schizophrenia.
AB  - BACKGROUND: Schizophrenia is a costly and complicated disorder to treat. A
      variety of schizophrenia treatment guidelines have been developed to provide
      valuable expert advice to practicing psychiatrists on various treatment options
      that are presumed to result in the best outcomes. However, examination of
      antipsychotic medication use patterns has suggested that current prescribing
      practices do not mirror recommended treatment guidelines and may have adverse
      economic consequences. AIM OF THE STUDY: This study seeks to describe
      antipsychotic medication treatment patterns and estimate the total costs of care
      associated with treatment patterns for individuals diagnosed with schizophrenia
      in usual care settings. METHODS: Use of outpatient antipsychotic medications and
      other health services during 1997 was obtained for 2,082 individuals with a
      diagnosis of schizophrenia in the IMS Health LifeLink employer claims database.
      We describe outpatient antipsychotic treatment patterns, estimated the costs of
      schizophrenia care by treatment pattern, and compared costs by treatment pattern
      using regression models. RESULTS: During 1997, 26% (n=536) of individuals
      diagnosed with schizophrenia received no antipsychotic medication in the
      outpatient setting, while 52% (n=1,088) were treated with only one antipsychotic
      (Monotherapy). For individuals who received more than one antipsychotic
      medication during 1997 (n=458), 13% (n=262) switched antipsychotic medications
      (Switch), 7% (n=154) augmented their original antipsychotic therapy with an
      additional antipsychotic (Augment), and 2% (n=42) of individuals were on more
      than one antipsychotic therapy at the start of the year. After adjusting for
      covariates, Switch and Augment patterns were associated with significant
      increases in total costs (an increase of 4,706 dollars (p<0.0001) and 4,244
      dollars (p=0.0002), respectively) relative to Monotherapy. DISCUSSION: These
      results indicate that a substantial proportion of individuals with a diagnosis of
      schizophrenia were not treated with or had low exposure to antipsychotic therapy.
      Individuals treated with antipsychotic monotherapy experienced nearly half the
      annual costs as individuals who were treated with antipsychotic polytherapy or
      who switched antipsychotic medications. These observations should be interpreted
      in the context of the study limitations. IMPLICATIONS FOR HEALTH CARE PROVISION
      AND USE: This analysis indicates that there may be considerable room for
      improvement in the treatment for individuals diagnosed with schizophrenia.
      IMPLICATIONS FOR HEALTH POLICIES: Though schizophrenia affects a very small
      portion of the population, the individual and societal burden associated with the
      disorder is quite high. This paper suggests that antipsychotic monotherapy and
      continuous therapy, commonly recommended by published treatment guidelines, may
      be associated with economic savings. IMPLICATIONS FOR FURTHER RESEARCH: Future
      research should evaluate the impact of newer antipsychotic medications on
      patterns of care and economic outcomes. More information is also needed on which
      individual patient characteristics are likely to predict success or failure on
      specific treatments. Finally, more detailed information on the reasons or
      rationale for switching or augmenting original pharmacotherapy would be valuable
      in improving medication management in these complex and often difficult to treat
      patients.

PMID- 14578540
TI  - Closing service system gaps for homeless clients with a dual diagnosis:
      integrated teams and interagency cooperation.
AB  - BACKGROUND: There is great concern about fragmentation of mental health service
      delivery, especially for dually diagnosed homeless people, and apprehension that
      such fragmentation adversely affects service access and outcomes. AIMS OF THE
      STUDY: This study first seeks to articulate two alternative approaches to the
      integration of psychiatric and substance abuse services, one involving an
      integrated team model and the other a collaborative relationship between
      agencies. It then applies this conceptualization to a sample of dually diagnosed
      homeless people who participated in the ACCESS demonstration. METHODS:
      Longitudinal outcome data were obtained through interviews at baseline, 3 months,
      and 12 months with homeless clients with a dual diagnosis (N = 1074) who received
      ACT-like case management services through the ACCESS demonstration. A survey of
      ACCESS case managers was conducted to obtain information on: (i) the proportion
      of clients who received substance abuse services directly from ACCESS case
      management teams, and the proportion who received services from other agencies;
      and (ii) the perceived quality of the relationship (i.e. communication,
      cooperation and trust) between providers--both within the same teams and between
      agencies. Hierarchical linear modeling was then used to examine the relationship
      of these two factors to service use and outcome with mixed-model regression
      analysis. RESULTS: Significant (p<.05) and positive relationships were observed
      in 4 of the 20 analyses of the association of service use and measures of
      communication, cooperation, and trust (either intrateam or inter-agency) while
      none were significant and negative. At 12 months, receipt of a higher proportion
      of services from agencies other than the ACCESS team was associated with fewer
      days homeless, and greater reduction of psychiatric symptoms, contradicting the
      hypothesis that integrated team care is more effective than interagency
      collaborations. DISCUSSION AND LIMITATIONS: This study broadens the conceptual
      framework for addressing service system fragmentation by considering both single
      team integration and interagency coordination, and by considering both program
      structure and the quality of relationships between providers. Data from a multi
      site outcome study demonstrated suggestive associations between perceptions of
      communication, cooperation and measures of clinical service use. However, the
      proportion of clients treated entirely within a single team was associated with
      poorer housing and psychiatric outcomes. These empirical results must be regarded
      as illustrative rather than conclusive because of the use of a non-experimental
      study design, imperfections in the available measures, and the incomplete
      sampling of case managers. IMPLICATIONS FOR HEALTH POLICY: This study suggests
      that fragmentation of services for dually diagnosed clients may be reduced by
      improving the interactions within and between agencies providing these services.
      While primary emphasis has been placed on developing integrated teams,
      interagency approaches should not be prematurely excluded. IMPLICATIONS FOR
      FUTURE RESEARCH: Research on approaches to reducing system fragmentation have
      focused on either global efforts to integrate numerous agencies in a community or
      highly focused efforts to develop specialized teams. Future research should also
      focus on the possibility of fostering constructive relationships between selected
      pairs or subsets of agencies. Research in this area will also benefit from the
      further development measures of team integration and of both intra-team and inter
      agency communication, collaboration, and trust.

PMID- 14578541
TI  - How mental health providers spend their time: a survey of 10 Veterans Health
      Administration mental health services.
AB  - BACKGROUND: Allocation of provider time across clinical, administrative,
      educational, and research activities may influence job satisfaction,
      productivity, and quality of care, yet we know little about what determines time
      allocation. AIMS: To investigate factors associated with time allocation, we
      surveyed all mental health providers in one Veterans Health Administration (VHA)
      network. We hypothesized that both facility characteristics (academic
      affiliation, type of organization of services, serving as a  hub  for treatment
      of severely mentally ill, facility size) and individual provider characteristics
      (discipline, length of time in job, having an academic appointment) would
      influence time allocation. METHODS: Eligible providers were psychiatrists,
      psychologists, social workers, physician assistants, registered or licensed
      practical nurses or other providers (psychology technicians, addiction
      therapists, nursing assistants, rehabilitation, recreational, occupational
      therapists) who were providing care in mental health services. A brief self
      report survey was collected from all eligible providers at ten VHA facilities in
      late 1998 (N = 997). Data regarding facility characteristics were obtained by
      site visits and interviews with managers. Multilevel modeling was used to examine
      factors associated with three dependent variables: (i) total time allocation by
      activity (clinical, administrative, educational, research); (ii) clinical time
      allocation by treatment setting (inpatient vs. outpatient); and (iii) clinical
      time allocation by type of care (mental vs. physical). Licensed Practical Nurses
      (LPNs) were used as the reference group for all analyses because LPNs were
      expected to spend the majority of their time on clinical activities. RESULTS:
      Overall, providers spent most of their time on clinical activities (77%),
      followed by administrative (11%), and educational (10%). Surprisingly, research
      activities accounted for only 2% of their time. Multilevel analysis indicated
      none of the facility-level variables were significant in explaining facility
      variance in time allocation, but individual characteristics were associated with
      time allocation. The model for predicting time allocation by inpatient or
      outpatient settings explained 16-18% of the variance in the dependent variable.
      In all models, provider discipline and length of time in job played an important
      role. Having an academic appointment was important only in the model examining
      total time allocation by activity type. DISCUSSION: These simple models explained
      only a small amount of variance in the three dependent variables which were
      intended to capture issues related to time allocation; and the low number of
      facilities limited our power to examine effects of facility-level factors. Our
      models performed better in predicting allocation of clinical time to treatment
      setting and type of treatment than in predicting overall time allocation.
      Discipline and length of time in job were significant across all models. In
      contrast, having an academic appointment was associated with allocating
      significantly less time to clinical activities and more time to administrative
      activities but not to any significant difference in time spent in either research
      or education. IMPLICATIONS: While a  gold standard  of optimal time allocation
      does not exist, it is striking that research, a stated mission of the VHA,
      accounted for so little of providers' time. The lack of involvement of clinicians
      in research has implications for recruitment and retention of high-quality mental
      health providers in this network and for the education of future providers.
      Without involvement of clinicians, research conducted in the network by
      nonclinicians may be less relevant to "real-world" clinical issues. Reductions of
      funds available to mental health, coupled with increased clinical demands, may
      have prompted this pattern of time allocation, and these findings attest to the
      challenges faced by large institutions that are charged with balancing many often
      seemingly competing missions.

PMID- 14578542
TI  - Mental disorder and substance abuse.

PMID- 14578543
TI  - Managed care, networks and trends in hospital care for mental health and
      substance abuse treatment in Massachusetts: 1994-1999.
AB  - BACKGROUND: Rates of inpatient care for mental health and substance abuse
      treatment have been reported to fall after the introduction of managed care, but
      the actual decline may be overstated. Almost all managed care impact studies are
      based on pre-post comparisons, which have two drawbacks: secular downward trends
      may be attributed to a managed care effect and self-selection may exaggerate the
      impact of managed care. Therefore it is useful to examine long-term population
      based trends in use associated with the growth of managed care. AIMS OF STUDY:
      This paper examines trends in inpatient care for mental health and substance
      abuse treatment in Massachusetts between 1994 and 1999 by service provider and
      payer. We analyze how managed care impacts the trends in mental health and
      substance abuse care. METHODS: We provide an overview of the health market in
      Massachusetts and compare trends in mental health and substance abuse services
      with all inpatient services. To analyze the impact of managed care, we compare
      the per discharge cost of managed care and fee for service plans in Medicare and
      Medicaid. Finally, we examine the role played by hospital networks in managed
      care. RESULTS: The reduction in service costs for mental health and substance
      abuse, about 25% in six years, is mostly due to the decline in the average cost
      per inpatient episode. This is only slightly greater than the decline in costs
      for all inpatient care. Managed care has reduced both the quantity (average
      length of stay) and intensity of health care (expenditure per day). Simulations
      suggest that the creation of hospital networks by managed care accounts for
      around 50% of the differential between the average costs of the HMO and FFS
      sectors. DISCUSSION: We find that the cost reductions in mental health and
      substance abuse services are larger than for physical health, but not by much.
      The average length of stay and average day cost is lower for managed care plans
      than for FFS plans, and much of this difference is attributable to the hospitals
      managed care plans select to participate in their networks. The data are limited
      to inpatient discharges from Massachusetts and therefore our conclusions may not
      be readily extended to other places. Furthermore, our analysis is based on the
      estimated cost rather than the actual payments to hospitals. IMPLICATION FOR
      HEALTH CARE PROVISION AND USE: The analysis highlights the importance of hospital
      selection and networks in affecting the cost of care. IMPLICATIONS FOR HEALTH
      POLICIES: Contrary to popular belief, the analysis shows that the experience of
      mental health and substance abuse and non-mental health and substance abuse
      services is similar. Creation of networks is an important strategy in managed
      care. IMPLICATIONS FOR FURTHER RESEARCH: This paper provides the groundwork for
      extending the analysis to areas with market characteristics different to those of
      Massachusetts. Further research should focus on the long-term trends in health
      outcomes between managed care and fee for service patients.

PMID- 14578544
TI  - The effect of chronic illness on the psychological health of family members.
AB  - BACKGROUND: Chronic illness in a family member can cause emotional distress
      throughout the family, and may impair the family's ability to support the
      patient. OBJECTIVES: We compare the familial impact of mental illness to other
      common chronic conditions. We examine the impact of a person's chronic illness on
      the psychological health of all persons in his or her family and identify both
      individual and family-level risk factors associated with psychological
      spillovers. METHODS: Our analysis is based on data from the 1996 Medical
      Expenditure Panel Survey (MEPS) that, because of its sample design, can be used
      to model both individual and family health status. Psychological distress is
      measured using responses to the general mental health question for each family
      member. The chronic conditions considered include cancer, diabetes, stroke
      related disorders, arthritis, asthma, and mental illness (including dementia). We
      estimate the relationships of interest using a semi-parametric method, the
      discrete random effects probit model. RESULTS: Brain-related conditions,
      including mental illness, impose the most significant risk to the psychological
      well-being of family members. The effects of the other chronic conditions
      studied, while not as significant, are notable in that their negative impacts on
      the psychological health of family members are sometimes larger than their direct
      psychological impacts on the patient. Economic distress not only directly
      increases the chance that an individual will experience emotional distress, but
      it appears it also reduces the family's ability as a whole to cope
      psychologically with chronic illness. DISCUSSION: Our analysis suffers from
      problems common to all cross-sectional designs, although the impact of selection
      bias appeared to be small in sensitivity analysis. While health conditions were
      based on unverified self-reports, condition categories were broadly defined to
      reduce the required precision of such reports. IMPLICATIONS FOR HEALTH CARE
      PROVISION AND USE: Because psychological distress is fairly contagious in
      families confronted with chronic illness, effective treatment strategies may need
      to be targeted to all members of the primary patient's family. Providers should
      be particularly vigilant for intra-family effects when their patients come from
      families that lack the financial resources that might protect against the stress
      of caring for a family member with a chronic illness. IMPLICATIONS FOR HEALTH
      POLICIES: Results suggest that, of the chronic conditions considered, priority
      for respite care and supportive services should be given to families in which a
      member has a brain-related disorder, particularly in families with limited
      financial resources and inadequate insurance coverage. IMPLICATIONS FOR FURTHER
      RESEARCH: The use of the discrete random effects probit model identified
      important interpersonal health effects that could not have been detected with
      standard analytical methods. The potential clinical relevance of the resulting
      findings underlies the need for additional data collection efforts that, like the
      MEPS, consider individuals in a family context.

PMID- 14578545
TI  - Efficacy and cost-effectiveness of the first generation of HIV prevention
      interventions for people with severe and persistent mental illness.
AB  - BACKGROUND: People with serious mental illness are at elevated risk for human
      immunodeficiency virus (HIV) infection. A small body of published research has
      evaluated the efficacy of HIV prevention interventions that aim to help persons
      with mental illness modify sexual behaviors that place them at risk for HIV
      infection. Additional research has evaluated the economic efficiency ('cost
      effectiveness') of these interventions. AIMS OF THE STUDY: We provide a detailed
      and critical review of the efficacy and cost-effectiveness of randomized,
      controlled trials of HIV prevention interventions for this population. We present
      a brief overview of the epidemiology of HIV among men and women with serious
      mental illness and describe HIV risk factors for members of this population. The
      efficacy literature is critically reviewed, and the results of the available
      studies are compared using a common effect size metric. The cost-effectiveness of
      HIV prevention interventions for mentally ill adults is then reviewed. METHODS:
      The efficacy of interventions at reducing risk behaviors and increasing
      preventive behaviors was summarized using effect size estimation techniques.
      First, we reviewed interventions that have been evaluated in randomized clinical
      trials and published in the peer-reviewed scientific literature so as to
      summarize the interventions that have been subjected to the most rigorous
      evaluation. For each of the five studies that met the inclusion criteria, we
      briefly described the methodology and intervention content, summarized the
      evidence for intervention efficacy, and calculated appropriate effect size
      estimates. A narrative review of two cost-effectiveness studies published to date
      was included. RESULTS: The review of intervention efficacy indicated that the
      risk reduction interventions evaluated to date have had only limited success at
      helping people with severe mental illness reduce their HIV risk behavior. Most
      effect sizes indicating successful condom use increases were in the small or
      small to moderate range. Overall, studies with the largest sample sizes, and
      presumably the most generalizable results, produced smaller intervention effect
      sizes than studies with smaller samples. The cost-effectiveness literature
      revealed similarly mixed results: economic efficiency varied from not cost
      effective to highly cost-effective. DISCUSSION: Limited information is presently
      available regarding the efficacy and cost-effectiveness of HIV prevention
      interventions for people with severe and persistent mental illness. Encouraging
      results were obtained in some, but not all studies. Methodological limitations
      will need to be addressed in the next generation of HIV risk reduction
      intervention studies for this population. IMPLICATIONS FOR HEALTH CARE PROVISION
      AND USE: Persons with severe mental illness warrant attention from health care
      providers due to elevated risk for HIV infection. Interventions discussed herein,
      focusing on information and behavioral skills training, can be employed until
      strategies with stronger results are developed. IMPLICATIONS FOR HEALTH POLICIES:
      Effective and cost-effective HIV risk reduction interventions are available for
      adults with mental illness and should be more widely implemented. The cost
      effectiveness of these interventions could be further enhanced by screening
      potential participants for high-risk sexual behaviors. IMPLICATIONS FOR FURTHER
      RESEARCH: To advance the field, the next generation of intervention research for
      people with severe mental illness will need to improve upon the designs and
      intervention strategies of the first generation, include larger samples, and
      devote increased attention to the life circumstances and particular mental health
      issues of intervention participants.

PMID- 14578546
TI  - Estimating the impact of alcohol policies on youth suicides.
AB  - BACKGROUND: Alcohol consumption has been identified as one of the most important
      risk factors for youth suicide. Previous research has shown a strong, empirical
      link between alcohol use and suicide. If alcohol use is a contributing factor in
      determining suicidal behaviors, then policies designed to reduce the alcohol
      consumption may succeed in reducing youth suicides as well. AIMS OF THE STUDY:
      This paper looks at the role of alcohol-related policies in reducing completed
      suicides by American youths and young adults. This hypothesis comes from two well
      established relationships: i) the observed correlation between alcohol
      consumption and incidents of suicide, and ii) the negative relationship between
      the full price of alcohol and consumption. The alcohol policies examined are
      excise taxes on beer, measures of alcohol availability, and drunk driving laws.
      METHODS: Data on completed suicides for each state in the United States are
      analyzed for the period 1976-1999. Negative binomial regressions are used to
      estimate a reduced form model of youth suicide. Suicides are analyzed by gender
      and age groups (ages 10-14, 15-19 and 20-24). RESULTS: The results indicate that
      increases in the excise tax on beer are associated with a reduced number of male
      suicides. This tax, however, has no impact on female suicides. Suicides by males
      ages 20-24 are positively related to the availability of alcohol, and negatively
      related to the presence of a 0.08 BAC (blood alcohol concentration) law and a
      zero tolerance law for drunk driving. Female suicides are not impacted by the
      availability of alcohol, although the drunk driving laws may impact suicides by
      teenage females. IMPLICATIONS FOR HEALTH POLICIES: Policies designed to reduce
      alcohol consumption may have the unintended benefit of reducing suicides,
      particularly among young males. IMPLICATIONS FOR FURTHER RESEARCH: While this
      research shows that alcohol policies may be successful in reducing male suicides,
      such policies have little impact on female suicides. Future research should
      explore other potential types of policies and programs to reduce female suicides.
      Also, illegal drug use has been linked to suicides in a similar manner as alcohol
      consumption. Future research should consider the role of illegal drug consumption
      and related policies in determining youth suicides.

PMID- 14578548
TI  - Consistency in performance evaluation reports and medical records.
AB  - BACKGROUND: In the health care market managed care has become the latest
      innovation for the delivery of services. For efficient implementation, the
      managed care organization relies on accurate information. So clinicians are often
      asked to report on patients before referrals are approved, treatments authorized,
      or insurance claims processed. What are clinicians  responses to solicitation for
      information by managed care organizations? The existing health literature has
      already pointed out the importance of provider  gaming,   sincere reporting,  
      nudging,  and  dodging the rules. AIMS OF THE STUDY: We assess the consistency of
      clinicians  reports on clients across administrative data and clinical records.
      METHODS: For about 1,000 alcohol abuse treatment episodes, we compare clinicians 
      reports across two data sets. The first one, the Maine Addiction Treatment System
      (MATS), was an administrative data set; the state government used it for program
      performance monitoring and evaluation. The second was a set of medical record
      abstracts, taken directly from the clinical records of treatment episodes. A
      clinician s reporting practice exhibits an inconsistency if the information
      reported in MATS differs from the information reported in the medical record in a
      statistically significant way. We look for evidence of inconsistencies in five
      categories: admission alcohol use frequency, discharge alcohol use frequency,
      termination status, admission employment status, and discharge employment status.
      Chi-square tests, Kappa statistics, and sensitivity and specificity tests are
      used for hypothesis testing. Multiple imputation methods are employed to address
      the problem of missing values in the record abstract data set. RESULTS: For
      admission and discharge alcohol use frequency measures, we find, respectively,
      strong and supporting evidence for inconsistencies. We find equally strong
      evidence for consistency in reports of admission and discharge employment status,
      and mixed evidence on report consistency on termination status. Patterns of
      inconsistency may be due to both altruistic and self-interest motives. DISCUSSION
      AND LIMITATIONS: Payment contracts based on performance may be subject to
      provider mis-reporting, which could seriously undermine its purpose. However,
      further analysis is needed to determine how much of the inconsistencies observed
      are results of clinician gaming in reporting. IMPLICATIONS FOR HEALTH POLICY:
      Increasing system accountability is becoming more and more important for health
      care policy makers. Results of this study will lead to a better understanding of
      physician reporting behavior. IMPLICATIONS FOR FUTURE RESEARCH: Our work in this
      paper on the data sets confirms the statistical significance of strategic
      reporting in alcohol addiction treatment. It will be of interest to confirm our
      finding in other data sets. Our on-going research will model the motives behind
      strategic reporting. We will hypothesize that both altruistic and financial
      incentives are present. Our empirical identification strategy will use Maine s
      Performance-Based Contracting system and client insurance sources to test how
      these incentives affect the direction of clinician s strategic reporting.

PMID- 14578549
TI  - Psychotherapy and pharmacotherapy in depression.
AB  - BACKGROUND: Depression is a condition with various modes of treatment, including
      pharmacotherapy, psychotherapy, and some combination of each. The role of
      psychotherapy in the treatment of depression relative to the role of
      pharmacotherapy is not well understood, and guidelines for psychotherapy in the
      primary care setting differ from guidelines for specialty care. There is little
      evidence concerning circumstances in actual practice that affect the use of
      psychotherapy in conjunction with pharmacotherapy. AIMS OF THE STUDY: We
      retrospectively identify the most important factors associated with the use of
      psychotherapy in combination with pharmacotherapy in the treatment of depression.
      Specifically, we study provider choice, health plan characteristics, and patient
      characteristics. METHODS: We use a comprehensive medical and pharmacy claims data
      sample of 1,023 individuals during 1992 1994. We select persons prescribed with
      an antidepressant medication and diagnosed with a depressive disorder by a
      primary care physician, psychiatrist, or non-physician mental health specialist.
      Controlling for depression diagnosis, comorbidity, and demographics, we examine
      the role of provider type and insurance plan benefit characteristics. We study
      the intensity of psychotherapy using zero-inflated count regression, the
      intensity of pharmacotherapy using truncated count regression, and the likelihood
      of treatment failure using logistic regression. RESULTS: Patients initially
      seeing a psychiatrist receive more than double the amount of psychotherapy and
      slightly more pharmacotherapy than patients of other providers. An additional
      prescription for antidepressant medication reduces by five percent the likelihood
      of treatment failure, but the amount of psychotherapy does not affect treatment
      failure. Patients seeing a psychiatrist are half as likely to have failed
      treatment, independent of any effect of psychotherapy. Case management and
      coinsurance rates do not affect the amount of psychotherapy, but the presence of
      case management positively affects the amount of pharmacotherapy and the
      likelihood of treatment failure. DISCUSSION: Although the amount of psychotherapy
      provided in conjunction with medication does not lower the rate of treatment
      failure, psychotherapy may nonetheless provide beneficial outcomes not studied
      here. Choice of a psychiatrist reduces the likelihood of treatment failure,
      independent of the number of psychotherapy sessions and antidepressant
      prescriptions. The effect of provider choice on treatment failure could be an
      artefact of differences in provider follow-up practices or could represent a
      difference in provider skills. Managed care strategies do not appear to reduce
      the intensity of depression treatment, but case management does increase the
      likelihood of treatment failure. IMPLICATIONS FOR HEALTH CARE PROVISION: Combined
      treatment with pharmacotherapy and psychotherapy appears to be individualized, as
      there is no pattern of more or less psychotherapy associated with antidepressant
      medication use. Choice of psychiatrist as the initial provider appears to reduce
      the likelihood of treatment failure, suggesting coordinated care may be
      beneficial. The link between psychiatrists and more psychotherapy is consistent
      with the hypothesis that patients resistant to treatment may nonetheless receive
      high quality care. IMPLICATIONS FOR HEALTH POLICIES: Managed care tools such as
      case management and coinsurance rates do not appear to restrict the use of either
      psychotherapy or pharmacotherapy. The association of case management with an
      increased likelihood of treatment failure suggests that plan characteristics can
      affect outcomes. IMPLICATIONS FOR FURTHER RESEARCH: Our study focuses on
      psychotherapy combined with medication and does not consider psychotherapy alone
      in the treatment of depression, which may be a preferred mode of treatment for
      some. Outcomes other than treatment failure, as well as costs, should also be
      considered. Our findings that psychiatrists are associated with a decreased
      likelihood of treatment failure and that case management is associated with an
      increased likelihood of treatment failure despite a correlation with greater
      pharmacotherapy intensity present avenues for additional study.

PMID- 14578551
TI  - Reconsideration of contemporary U.S. drug policy.
AB  - In their recent book Drug War Heresies: Learning From Other Vices, Times, and
      Places (Cambridge: Cambridge University Press, 2001), MacCoun and Reuter
      challenge the continuation of contemporary U.S. drug policy. Depenalization and
      legalization of illicit drugs are evaluated as alternatives to U.S. prohibition
      policy, with harm reduction (mitigation of social damages) as the criterion for
      guiding drug regime change. The appraisal encompasses an analysis of underlying
      philosophical and social mechanisms of current U.S. policy as well as drawing
      analogies from a comprehensive review of American vices and also Western European
      governmental interventions into illicit drug activities. What is apparent is that
      the evaluation and the available evidence entail substantial complexity and do
      not readily present unequivocal positions. The evaluation also strongly indicates
      that considerable difficulty would be encountered not only for the implementation
      of alternative regimes but also for the engagement in open political discussion
      of prohibition alternatives.

PMID- 14578550
TI  - Managed care and the quality of substance abuse treatment.
AB  - BACKGROUND: In the US, the spiraling costs of substance abuse and mental health
      treatment caused many state Medicaid agencies to adopt managed behavioral health
      care (MBHC) plans during the 1990s. Although research suggests that these plans
      have successfully reduced public sector spending, their impact on the quality of
      substance abuse treatment has not been established. AIMS OF THE STUDY: The
      Massachusetts Medicaid program started a risk-sharing contract with MHMA, a
      private, for-profit specialty managed behavioral health care (MBHC) carve-out
      vendor on July 1, 1992. This paper evaluates the carve-out s impact on spending
      per inpatient episode and three proxy measures of quality: (i) access to
      inpatient treatment (ii) 30-day re-admissions and (iii) continuity of care.
      METHODS: Medicaid claims for inpatient treatment were collapsed into episodes.
      Clients were tracked across the five-year period and an interrupted time series
      design was used to compare the three quality outcomes and spending in the year
      prior to (FY1992) and the four years during MHMA (FY1993-FY1996). Logistic and
      linear regression models were used to control for race, disability status, age,
      gender and primary diagnosis. RESULTS: Despite a 99% reduction in the use of
      hospital-based settings, access to 24-hour services overall increased by 38%,
      largely due to an expansion in the use of freestanding detoxification and acute
      residential services. Continuity improved by 73%. Nevertheless, rates of 7-day
      (58%) and 30-day (24%) readmission increased significantly, even after
      controlling for increases in disability status. Per episode spending decreased by
      76% ($2,773), characterized by a dramatic spending reduction in FY1993 that was
      maintained but not augmented in subsequent years. DISCUSSION: The carve-out had
      mixed effects on the quality of substance abuse treatment. While one of the three
      measures (readmission rates) deteriorated, two improved (access and continuity).
      IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: Rapid re-admissions were strongly
      associated with shorter lengths of stay, suggesting that strengthening discharge
      planning may preserve the benefits of MBHC while avoiding its risks. IMPLICATIONS
      FOR HEALTH POLICIES: Since reductions in Medicaid spending were impressive but
      finite, MBHC may not be the permanent solution to inflation in behavioral health
      care. MBHC firms should implement quality-monitoring programs to ensure that
      aggressive utilization management strategies do not compromise quality of care.
      IMPLICATIONS FOR FURTHER RESEARCH: The impact of managed behavioral health care
      should ideally be evaluated in randomized controlled studies. In addition,
      research is needed to establish that the quality measures employed in this
      evaluation - improved access, enhanced continuity and fewer rapid re-admissions  
      actually correspond to reductions in drug or alcohol use and other favorable
      outcomes obtained through client self-report or urinalysis.

PMID- 14578552
TI  - Cutaneous type of adult T cell leukemia/lymphoma: a new entity among cutaneous
      lymphomas.
AB  - Adult T cell leukemia/lymphoma (ATL) is a malignancy of CD4+ T cells that is
      endemic in certain areas in Japan. Two types of cutaneous ATL thought to
      originate from skin include cutaneous tumor and erythematopapule types. Patients
      with cutaneous ATL show neither leukemic involvement nor invasion of tumor cells
      into the lymph nodes for at least six months. The differential diagnosis between
      cutaneous ATL and mycosis fungoides is often difficult. The presence of
      monoclonal integration of human T lymphotropic virus-I proviral DNA in skin
      samples is of definitive diagnostic value in cutaneous ATL.

PMID- 14578553
TI  - Topical antibacterial agents in dermatology.
AB  - Topical antibacterials are being widely used for the treatment or prevention of
      superficial bacterial infections. Emergence of drug resistant mutant strains of
      microorganisms and development of irritant and allergic contact dermatitis is a
      common problem with many of the topical antibacterials. Topical antibacterials
      are being reviewed with special emphasis on their spectrum of activity,
      resistance patterns, contact sensitivity potential and clinical uses. Factors
      which help the physician to choose a particular antibacterial for the specific
      indication in order to have the maximum efficacy and minimum adverse effects are
      discussed.

PMID- 14578554
TI  - Pattern of contact sensitivity in Indian patients with hand eczema.
AB  - One hundred consecutive patients with hand eczema were patch tested with the
      Indian Standard Series and indigenous antigens after a detailed history and
      clinical examination. Both sexes were involved and the majority of them were in
      the age group between 20-39 years (56%). Their occupational profile varied in
      order of frequency from household work (37%), to masons (14%), students (11%),
      factory workers (7%), and others (31%). Itching was the most common presenting
      complaint (93%). A history of atopy was found in 36% of the patients. The
      predominant sites involved were the palms (43%), followed by fingers (32%),
      dorsum (17%), and the entire hand (8%). Dry, scaly skin was the most common
      morphological picture, followed by hyperpigmentation, fissuring, and
      lichenification. Based on history, clinical examination and patch test results,
      the diagnosis was made as allergic contact dermatitis in 67% of cases and
      irritant contact dermatitis in 15% of cases. Positive patch tests with one or
      more allergens were noted in 67% of the patients. Vegetables (21%) were found to
      be the most common sensitizers, followed by nickel sulphate (20%), potassium
      dichromate (18%), and others. Wet work, soaps, and detergents were found to be
      the most offending irritants. The present study confirmed the fact that hand
      eczema is a multifactorial disease caused by both irritants and allergens.

PMID- 14578555
TI  - Structural changes in the glycosaminoglycan chain of rat skin decorin with
      growth.
AB  - Decorin controls collagen fibrilogenesis in skin, and its molecular weight
      changes in wound healing and with age. In this report, the quantitative and
      structural changes of decorin were investigated with growth in rat skin from the
      fetus to the young adult. A northern blot analysis showed that the highest level
      of skin decorin mRNA was at post partus 0.5 days; this level was about 3.7 times
      the level at embryo 16.5 days. The mRNA level in the rat skin decreased by 1/5
      from post partus 0.5 days until 90 days of age. Western blotting showed that the
      amount of decorin increased with age in protein level. The molecule size of
      decorin at embryo 18.5 days was about 110 kDa, and that at post partus 90 days
      was about 70 kDa. There were no changes in molecular size of its core protein, so
      the reduction in the size of decorin was dependent on the size of the
      glycosaminoglycan (GAG) as shown by western blot analyses. Electron micrography
      of the rat skin with cupromeronic blue staining showed that the length of GAG at
      embryo 18.5 days was about 78.58 +/- 13.94 nm, and that at post partus 90 days
      was about 54.05 +/- 4.79 nm. The reduction in length of decorin GAG with age
      shrunk the distance between the collagen fibrils. We suggested that decorin
      changes the GAG length in order to control skin reconstruction in response to
      inflammation and injury.

PMID- 14578556
TI  - The expression of melanogenic proteins in Korean skin after ultraviolet
      irradiation.
AB  - For proper melanin production, several specific enzymes such as tyrosinase,
      tyrosinase-related protein 1 (TRP-1) and dopachrome tautomerase are required.
      Their expressions are increased after exposure to UVB. However, it is not known
      how long tyrosinase and TRP-1 activities continue after UV irradiation in vivo.
      The purpose of this study is to measure the changes in expressions of tyrosinase,
      TRP1, and MITF after exposure to UV on skin in a Korean population. We
      established an immunohistochemical staining protocol for specimens which were
      obtained from UV-irradiated skin in five healthy Korean males on the 2nd, 5th,
      7th, 28th, and 56th days after UV irradiation. Tyrosinase, TRP-1, and MITF
      expressions increased until 7 days after UV irradiation and then dropped to the
      basal constitutive level 4 and 8 weeks later. Interestingly, tyrosinase increased
      prior to TRP-1. This study reveals the time-sequence of melanin-synthesized
      enzymes and provides important information for the clinical evaluation of the
      effectiveness of whitening agents.

PMID- 14578557
TI  - Skin graft fixation with negative-pressure dressings.
AB  - The tie-over bolster dressing is the most commonly used method for securing skin
      grafts. However, it requires surgical skill and experience to make a skin graft
      adhere closely to a grafting site when the site has a complicatedly curved
      surface. The lack of appropriate tension and pressure on the skin graft may
      produce hematoma, dislocation, or wrinkles in the graft. The grafting site for
      the dorsum of a hand is particularly complicated and irregular and requires
      delicate changes in pressure when the tie-over bolster dressing is used for sites
      supported and not supported by bones. We have obtained a high survival rate at
      such difficult sites by managing skin grafts with negative-pressure dressings.
      This paper describes the details of the technique with case reports. We have used
      this technique for skin graft fixation in 10 patients and confirmed its high
      utility as evidenced by a survival rate of 95% or higher of the grafted areas.
      Unlike existing techniques that apply pressure on skin grafts, this technique
      applies a negative pressure to the space between the skin graft and the grafting
      site to remove hematomas and pull the whole skin graft onto the grafting site
      with uniform force for adhesion.

PMID- 14578558
TI  - Melkersson-Rosenthal syndrome caused by saprodontia: a case report.
AB  - A 24-year-old female patient with Melkersson-Rosenthal syndrome (MRS) in
      association with saprodontia is reported. She presented with lower labial
      swelling and left facial edema. Histological examination of the involved oral
      mucosa showed a noncaseating epithelioid granuloma. Results from the laboratory
      and imaging examinations were normal or negative. Her orofacial swelling
      disappeared after treatment of the saprodontia of the left first molar.

PMID- 14578559
TI  - Primary cutaneous follicle center cell lymphoma of the scalp successfully treated
      with anti CD20 monoclonal antibody and CHOP combination therapy with no
      subsequent permanent loss of hair.
AB  - We present a primary cutaneous follicle center cell lymphoma (PCFCCL) patient who
      was successfully treated with Rituximab, a new anti-CD20 monoclonal antibody. A
      thirty-two-year-old male developed two asymptomatic tumors on the scalp.
      Histopathologically, the tumors were composed of diffuse and nodular infiltration
      of centrocytes and centroblasts. Immunohistopathologically, the tumor cells
      stained positively with anti-CD20 antibody and anti-kappa antibody, but not with
      anti-CD5, anti-CD10, or anti-Bcl-2 antibody. Radiation therapy is effective in
      treating PCFCCL; however, it usually results in the permanent loss of hair. This
      patient was treated with Rituximab and CHOP, and achieved a complete remission.
      He has had no recurrence in more than 12 months and no permanent loss of hair on
      the scalp.

PMID- 14578560
TI  - Multicentric Castleman's disease associated with inherited epidermolysis bullosa.
AB  - Multicentric Castleman's disease (MCD) is a rare disorder characterized by fever,
      polyclonal hypergammaglobulinemia, and generalized lymphadenopathy. It has three
      histological characteristics: a recognizable architecture, germinal center
      abnormalities, and plasmacytosis. Inherited epidermolysis bullosa (EB) is also a
      rare disorder caused by a genetic defect. We report a 43-year-old patient with
      dystrophic EB, non-Hallopeau-Siemens recessive type or dominant type, displaying
      clinicopathologic features of MCD. In addition, his serum interleukin-6, which is
      thought to be responsible for the clinical symptoms in MCD, was elevated.

PMID- 14578561
TI  - Bullous scabies mimicking bullous pemphigoid.
AB  - Scabies is an infestation caused by Sarcoptes scabiei and characterised by
      polymorphous lesions that may include burrows, papules, nodules, excoriation and
      crusts. Vesicular and bullous lesions are rather rare. Several diseases may be
      confused with scabies. We report a case of bullous scabies which, on the basis of
      the clinical and histopathological picture, mimicked bullous pemphigoid. Direct
      and indirect immunofluorescence were negative. Bullae recurred and persisted
      despite systemic corticosteroids. The patient was successfully treated with 5%
      permethrin and remained disease free for up to 12 months of follow-up.

PMID- 14578562
TI  - Dermatological side effects of brimonidine: a report of three cases.
AB  - Brimonidine is a potential first line therapy for primary open angle glaucoma
      (OAG) and ocular hypertension (OHT). It is known to cause various ocular and
      systemic side effects. Being a newer drug, the whole spectrum of its adverse
      effects is not known. The dermatological side effects caused by brimonidine have
      rarely been reported before. We present three OAG patients who presented to us
      with contact dermatitis of periorbital skin and lichen planus of nail following
      the use of topical brimonidine (0.2% twice a day) for more than six months. These
      side effects slowly disappeared on discontinuing the drug but reappeared on
      reintroducing topical formulation. Such side effects from the use of brimonidine
      have not been reported before.

PMID- 14578563
TI  - Anaphylaxis due to tosufloxacin tosilate.

PMID- 14578564
TI  - Molecular architecture of the sperm flagella: molecules for motility and
      signaling.
AB  - Sperm motility is generated by a highly organized, microtubule-based structure,
      called the axoneme, which is constructed from approximately 250 proteins. Recent
      studies have revealed the molecular structures and functions of a number of
      axonemal components, including the motor molecules, the dyneins, and regulatory
      substructures, such as radial spoke, central pair, and other accessory
      structures. The force for flagellar movement is exerted by the sliding of outer
      doublet microtubules driven by the molecular motors, the dyneins. Dynein activity
      is regulated by the radial spoke/central pair apparatus through protein
      phosphorylation, resulting in flagellar bend propagation. Prior to fertilization,
      sperm exhibit dramatic motility changes, such as initiation and activation of
      motility and chemotaxis toward the egg. These changes are triggered by changes in
      the extracellular ionic environment and substances released from the female
      reproductive tract or egg. After reception of these extracellular signals by
      specific ion channels or receptors in the sperm cells, intracellular signals are
      switched on through tyrosine protein phosphorylation, Ca2+, and cyclic nucleotide
      dependent pathways. All these signaling molecules are closely arranged in each
      sperm flagellum, leading to efficient activation of motility.

PMID- 14578565
TI  - Endocrine control of the reproductive activity in hibernating bats.
AB  - Bats, Chiroptera, constitute the second largest order of the class Mammalia and
      vary greatly in habitats, available foods and mating systems. The timing,
      duration and patterns of reproduction in bats vary considerably among species and
      different localities. Though much is known about the reproductive phenomena and
      associated endocrine characteristics of various species, the central mechanism
      regulating the peculiar delay and asynchrony in reproductive activity remains to
      be elucidated. The current understanding on the endocrine characteristics and
      possible mechanism of regulation of the hypothalamo-adenohypophysial-gonadal axis
      of bats will be reviewed, based mainly on our own studies in hibernating
      rhinolophid bats.

PMID- 14578566
TI  - Visualization of erythrocytes in the zebrafish brain.
AB  - We found that erythrocytes of zebrafish have cytoplasmic peroxidase activity.
      Blood in the zebrafish brain was visualized using a standard peroxidase staining
      method after formaldehyde fixation. The erythrocytes in the brain were heavily
      stained, but neurons and glias were not stained at all. This easy method enables
      the distribution of erythrocytes in the whole brain to be determined, and enables
      the actual number of erythrocytes in each area in the brain to be calculated. The
      paths of major, thick blood vessels in zebrafish brain are similar to those in
      higher vertebrates, however, the distribution of thin blood vessels is different.
      We also found that the erythrocytes were unevenly distributed in the brain. For
      example, the density of erythrocytes in the surface layer of the tectum was more
      than 30-fold higher than in the deeper granular layer. Very few erythrocytes were
      found in bundles of axons like cranial nerves and the medial longitudinal
      fascicle. In general, fewer erythrocytes were found in areas near the ventricle,
      whereas many more were found closer to the surface of the brain. The distribution
      of erythrocytes in the brains of sleeping, awake and actively moving fish were
      compared. In the brains of sleeping fish, most of the erythrocytes were present
      in large vessels. This was not observed in brains of awake or actively moving
      fish. We found that the blood supply to motor neurons in the ventral horn of the
      spinal cord increased during active movement compared to that in awake or
      sleeping fish.

PMID- 14578567
TI  - The impact of deafness to the survival of the newborn cells in the brain of
      juvenile white-rumped munia, Lonchura striata.
AB  - In white-rumped munia, early auditory experience is critical for normal song
      development. New neurons are constantly added to the telencephalon in juveniles.
      We examined the potential role of auditory experience in regulating the
      developmental changes in the song nuclei and the survival of newborn cells. We
      chose two special days, postnatal day 23 and 37, at which we deafened the birds
      through bilateral cochlea removal. All birds were injected with the cell birth
      marker BrdU two weeks before the lesion surgeries, and then were killed two weeks
      or one month later. The BrdU-positive cells were distributed throughout the
      brain, including the high vocal center (HVC), Lobus parolfactorius and the
      ventricle zone (VZ) in telencephalon, the granular cell layer (GCL) of
      cerebellum. Moreover, these BrdU-positive cells in the GCL could self-renew.
      However, the nucleus robustus archistriatalis (RA) did not sprout new neurons in
      juvenile. In telencephalon except the VZ, 41 percent of BrdU-positive cells were
      NeuN-positive, too. Deafness had no significant effect on development of HVC and
      RA, the distribution of new cells, and the survival of new cells in
      telencephalon. From these data, we propose that auditory deprivation could not
      affect the survival of new cells of telencephalon within one month. Surprisingly,
      we found deafness had a complex and dramatic effect on the number of new cells in
      cerebellum. Deafness at postnatal day 23 could increase the number of new cells
      in the GCL, while deafness at postnatal day 37 decreased the number.

PMID- 14578568
TI  - Significance of affinity and cooperativity in oxygen binding to hemoglobin of
      horse fetal and maternal blood.
AB  - The physiological significance of the position and shape of the oxygen
      equilibrium curve (OEC) of horse hemoglobin (Hb) is considered from the viewpoint
      of oxygen (O2) transport efficiency and the effectiveness of the Bohr effect. In
      horse fetal and maternal bloods, their physiological O2 affinities are nearly
      optimized with respect to the effectiveness of the Bohr shift occurring at the O2
      release site, when it is measured by the change in O2 saturation per unit change
      in P50. With relatively low cooperativity (n=2.69) of horse Hb under
      physiological conditions, the effectiveness of the Bohr shift for fetal blood at
      O2 uptake site and maternal blood at O2 release site is high. These facts imply
      that the position and the cooperativity of horse Hb OEC are optimized to receive
      maximal benefit from the double Bohr shift. Before exercise, the position of the
      OEC for adult mares is nearly optimized for the effectiveness of the Bohr shift
      occurring at the O2 release site, whereas, at maximal exercise, the position of
      the OEC tends to become advantageous for O2 transport efficiency.

PMID- 14578569
TI  - Embryonic development of the Pacific lamprey, Entosphenus tridentatus.
AB  - Embryonic development of the Pacific lamprey, Entosphenus tridentatus, from Japan
      is described. Egg sizes averaged 1.249 mm (longest axis) and 1.145 mm (shortest
      axis), the time required for hatching being 11 days at 18 degrees C, shorter than
      previously reported for a lower water temperature (19 days at 15 degrees C).
      Early development in E. tridentatus proceeded at a similar rate to that in other
      lampreys, in spite of different rearing water temperatures for the latter,
      indicating possible specific differences in basic developmental rates.

PMID- 14578570
TI  - Ultrastructural and cytochemical aspects of metamorphosis in the midgut of Apis
      mellifera L. (Hymenoptera: Apidae: Apinae).
AB  - The midgut of Apis mellifera is remodeled during metamorphosis. The epithelium
      and, to a lesser extent, the muscular sheath degenerate between the end of the
      last larval instar and the onset of pupation (prepupa). The larval epithelium is
      shed to the midgut lumen and digested, while a new epithelium is reconstructed
      from larval regenerative cells. During pupation, some reorganization still
      occurs, mainly in brown-eyed pupae. In pharate adult, the midgut wall shows the
      characteristics of adult, although some cells have pycnotic nuclei. The
      localization of alkaline and acid phosphatases showed that these enzymes were not
      involved in the reabsorption of the midgut wall.

PMID- 14578571
TI  - Fasting reduces plasma leptin-and ghrelin-immunoreactive peptide concentrations
      of the burbot (Lota lota) at 2 degrees C but not at 10 degrees C.
AB  - The effects of fasting at two water temperatures (2 and 10 degrees C) on plasma
      leptin- and ghrelin-immunoreactive peptide concentrations and energy metabolism
      were investigated in the burbot (Lota lota), a freshwater gadoid, which lives in
      cold waters and tolerates long periods of fasting. Burbot were assigned to fed
      and fasted groups at 2 and 10 degrees C. Leptin- and ghrelin-immunoreactive
      peptides were identified in burbot plasma. Fasting at 2 degrees C reduced the
      plasma leptin- and ghrelin-immunoreactive peptide concentrations and reduced the
      relative liver weights and the liver and muscle glycogen concentrations. The
      concentrations of the leptin- and ghrelin-immunoreactivities correlated
      positively with each other. At 10 degrees C there were decreased plasma thyroxine
      levels in both sexes, and slightly lower plasma testosterone concentrations in
      males. The results support previous studies in stating that immunoreactivities
      resembling mammalian leptin and ghrelin can be detected in burbot plasma and
      liver, but the specific functions of these peptides will have to be determined in
      future studies.

PMID- 14578572
TI  - Five different types of putative GnRH receptor gene are expressed in the brain of
      masu salmon (Oncorhynchus masou).
AB  - Recent studies have shown that there are multiple genes encoding gonadotropin
      releasing hormone receptor (GnRH-R) in single species. In salmonids, however,
      only a single gene has been identified in the rainbow trout. We therefore
      isolated partial cDNAs from the brain and the pituitary of masu salmon
      Oncorhynchus masou by reverse transcription-polymerase chain reaction and 5'
      rapid amplification of cDNA ends, using primers corresponding to conserved
      transmembrane domains (TMs). Five different partial cDNAs were isolated from an
      individual and termed as msGnRH-R1, R2, R3, R4 and R5. They are divided into two
      groups, msGnRH-R1, R2, R3 and msGnRH-R4, R5. Two groups share 59-71% nucleotide
      sequence identities. Phylogenetic analysis showed that the former group is
      closely related to the goldfish GnRH-R GfA, and the latter to GfB. All five
      msGnRH-R genes were expressed in the brain and msGnRH-R1, R3 and R5 were
      expressed in the pituitary. In addition, we found mRNA for msGnRH-R1 in the
      kidney and ovary, and R2 in the ovary, whereas msGnRH-R5 gene was widely
      expressed in the muscle, heart, kidney and testis. Differences in the expression
      of msGnRH-R genes between maturing and spawning fish were observed in the brain
      and pituitary, except for the constantly expressed msGnRH-R5. A splicing variant
      of msGnRH-R1 mRNA that is capable of generating a truncated GnRH-R that consists
      of 5TMs was also expressed in the brain, pituitary and kidney. These results
      indicate that five different types of putative GnRH-R gene are present and
      expressed in the brain of masu salmon.

PMID- 14578573
TI  - Detection, analysis and interactions of plasma ghrelin, leptin and growth hormone
      in the mink (Mustela vison).
AB  - The aim of this study was to obtain basic knowledge of the plasma concentrations
      and interactions of weight regulatory hormones in juvenile minks (Mustela vison).
      Ghrelin, leptin, and growth hormone (GH) levels were validated and determined by
      radioimmunoassay methods from the plasma of 30 female and 30 male minks. The
      female minks had higher plasma ghrelin and GH levels than the males. The plasma
      ghrelin concentrations of the females correlated positively with their body
      masses (BMs). The plasma leptin levels did not differ between sexes, but there
      was a positive correlation between the plasma leptin concentrations and BMs in
      the male minks. When the data from the male and female minks were combined, the
      correlation between the leptin levels and the BMs was still clear, but this was
      not observed in the females alone. In the male minks, the plasma GH levels
      correlated positively with the BMs and with the plasma leptin concentrations.
      However, there was no correlation between the plasma ghrelin and GH or leptin
      concentrations. The hormone concentrations were quite similar to earlier
      measurements in other carnivores.

PMID- 14578574
TI  - Effects of highly or relatively selective 5-HT1A receptor agonists on lordosis in
      female rats.
AB  - To investigate the role of serotonin (5-HT) receptor 1A or 7 in regulating
      lordosis behavior in female rats, ovariectomized rats were treated with 3 kinds
      of receptor agonists and lordosis behavior was observed. The injected agents were
      the selective 5-HT1A receptor agonist, buspirone (BUS), the highly selective 5
      HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin ((+/-)8-OH-DPAT),
      and the 5-HT1A and 5-HT7 receptor agonist, (R)-8-hydroxy-2-(di-n
      propylamino)tetralin ((+)8-OH-DPAT). A behavioral test was performed after
      ovariectomy and subcutaneous implantation of a silicon tube containing estradiol.
      Female rats in which the lordosis quotient (LQ) was over 70 were
      intraperitoneally injected with several doses of these agents. As a result, in
      the BUS group, the dose of 3 mg/kg bw, but not 1 mg/kg was effective for
      suppressing lordosis. On the other hand, an inhibitory effect was observed from
      0.25 mg/kg and 0.5 mg/kg in the (+)8-OH-DPAT and (+/-)8-OH-DPAT groups,
      respectively. In the time-course experiment, in all drug-treated groups, LQ
      decreased to lower than 20 after 15 min and low LQ continued for 1 hr at least.
      Measurement of locomotor activity using an infrared sensor system showed no
      relation between the decrease in lordosis by these agents and spontaneous
      locomotion. These results indicate that 5-HT1A is strongly involved in the
      lordosis-inhibiting circuit of the serotonin neurons.

PMID- 14578576
TI  - Studies on Japanese botryllid ascidians. IV. A new species of the genus Botryllus
      with a unique colony shape, from the vicinity of Shimoda.
AB  - The morphology and life history of a strange and unidentified botryllid ascidian
      were investigated. This ascidian was first collected from the stony shore of
      Ebisu Island in Shimoda, a city on Izu peninsula in central Japan. Unlike other
      botryllid ascidians, whose colonies are flat and smooth, this ascidian's colonies
      are rugged. In each colony, zooids are arranged into several oval systems, each
      of which has a thick part containing zooids and very thin parts that do not. The
      arrangement of ovary and testis in this species is the same as in other species
      of the genus Botryllus; the ovary is situated anterior to the testis. The embryo
      of this ascidian develops in the peribranchial cavity of its mother zooid without
      any brooding organs, as is the case with Botryllus scalaris and Botryllus
      puniceus. Meanwhile, the results of cut colony assay experiments did not show the
      existence of colony specificity in this ascidian. Even when two syngeneic
      colonies were brought into contact at their growing edges, none fused together.
      On the other hand, when two colonies were brought into contact with each other at
      their cut surfaces, they always fused into a single colony, regardless of their
      origin. Therefore, this species may be the only species that lacks colony
      specificity among the botryllids studied so far.

PMID- 14578575
TI  - Molecular cloning and expression of prohormone convertases PC1 and PC2 in the
      pituitary gland of the bullfrog, Rana catesbeiana.
AB  - We cloned cDNAs encoding PC1 and PC2 from a cDNA library constructed for the
      anterior pituitary gland of the bullfrog (Rana catesbeiana) and sequenced them.
      The bullfrog PC1 cDNA consisted of 2972 base pairs (bp) with an open reading
      frame of 2208 bp and encoded a protein of 736 amino acids, including a putative
      signal peptide of 26 amino acids. The protein showed a high homology to R.
      ridibunda PC1 (95.1%) and mammalian PC1 (72.6%). The bullfrog PC2 cDNA consisted
      of 2242 bp with an open reading frame of 1914 bp and encoded a protein of 638
      amino acids, including a putative signal peptide of 23 amino acids. This protein
      showed a high homology to R. ridibunda PC2 (95.5%) and mammalian PC2 (84.8%). The
      catalytic triad of serine proteinases of the subtilisin family was found at Asp
      168, His-209, and Ser-383 in the PC1 protein and at Asp-167, His-208, and Ser-384
      in the PC2 protein. In situ hybridization staining revealed that PC2 mRNA was
      detected in corticotrope cells of the tadpoles, but not in those of the adults.
      In the adult, only PC1 mRNA was detected in the pars distalis but both PC1 and
      PC2 mRNAs were detected in the pars intermedia. The data also showed that PC1
      mRNA was expressed in gonadotrope cells.

PMID- 14578577
TI  - A new species of lentic breeding Korean salamander of the genus Hynobius
      (Amphibia, Urodela).
AB  - A new species of salamander, Hynobius yangi, is described from Kori (=Hyoam-ri),
      Busan-shi, southeastern Korea. It is a lentic breeder belonging to the H.
      nebulosus species group, and has long been confused with another Korean species
      H. leechii. The new species, however, is genetically substantially differentiated
      from Korean and Japanese relatives. Hynobius yangi is morphologically very
      similar to H. leechii, but could be differentiated from it by the tail shape,
      degree of limb separation, shape of vomerine teeth series, shape of egg sac, and
      dorsal coloration.

PMID- 14578578
TI  - A new species of Euzonus (Polychaeta: Opheliidae) from subtidal zones in Japan.
AB  - A new opheliid polychaete, Euzonus japonicus sp. nov., is described. This species
      was collected from subtidal zones in Japanese coasts, while most Euzonus species
      inhabit intertidal sandy beaches. E. japonicus sp. nov. is morphologically most
      similar to another subtidal species, E. flabelliferus (Ziegelmeier, 1955)
      collected from northern Europe, but different from that in the form of branchiae.
      They share a unique characteristic on setiger 10, i. e., a pair of lateral
      transverse rows of conical cirri, instead of a pair of lateral smooth ridges that
      are common to all intertidal Euzonus species.

PMID- 14578579
TI  - Ascorbic Acid: a promising memory-enhancer in mice.
AB  - Alzheimer's disease is a progressive neurodegenerative disorder characterized by
      a gradual decline in memory. The occurrence of Alzheimer's disease is commonplace
      among the Asian population, particularly among senior citizens. The present study
      was undertaken to assess the potential of ascorbic acid as a memory-enhancer.
      Swiss mice of either sex were employed in the present investigation. Elevated
      plus-maze and passive-avoidance apparatus served as the exteroceptive behavioral
      models, and diazepam-, scopolamine-, and aging-induced amnesia served as the
      interoceptive behavioral models. Ascorbic acid (60, 120 mg/kg) injected for 3 and
      8 consecutive days improved learning and memory of aged mice as indicated by
      decreased transfer-latency and increased step-down latency. Furthermore, ascorbic
      acid provided protection to the young animals from scopolamine- and diazepam
      induced impairment of memory. Ascorbic acid was found to be more potent than
      piracetam as reflected by the smaller dose, more pronounced effect, and quicker
      onset of action. Ascorbic acid has shown promise as a powerful memory-improving
      agent particularly effective in aged animals. Hence, ascorbic acid might prove to
      be a useful memory-restorative agent in the treatment of dementia seen in elderly
      individuals. The underlying mechanism of action of ascorbic acid may be
      attributed to its antioxidant property.

PMID- 14578580
TI  - Pilot study of topical delivery of mono-L-aspartyl chlorin e6 (NPe6): implication
      of topical NPe6-photodynamic therapy.
AB  - Photodynamic therapy (PDT) is an evolving cancer treatment with promising results
      in treating malignant tumors by photoactivation of a photosensitizer with a
      specific wavelength. The second generation photosensitizer mono-L-aspartyl
      chlorin e6 (NPe6) was reported to have significant efficacy in killing cancer
      cells in vitro and in vivo. Though topical application might yield a higher local
      concentration and less systemic side effect, no data concerning topical
      absorption of NPe6 is available even though the drug has already been used in
      clinical trial for several years. To evaluate the possibility of topical delivery
      of NPe6 via an animal model, escalated concentrations of NPe6 were applied to
      BALB/c mouse skin for a different time periods after barrier disruption with tape
      stripping. Since NPe6 fluorescence intensity and drug concentration in tissue was
      well correlated, we evaluated drug penetration depth with frozen sections of
      treated and non-treated skin under a fluorescence microscope. An on-line
      fluorescence imaging system was used to monitor the NPe6 fluorescence kinetics in
      the skin. The fluorescence microscope confirmed successful topical delivery of
      NPe6 in mouse skin with or even without barrier disruption. Orange to red NPe6
      fluorescence appeared at the epidermis, dermis, and even the muscular layer when
      using 10 mg/ml NPe6 application. The fluorescence intensity peaked at 1 h and
      revealed a dose-dependent response pattern. NPe6 treated versus non-treated skin
      showed a statistically significant difference by Student's t-test (P<0.05). The
      results described here suggest that topical delivery of NPe6 is possible. It
      showed fast and deep penetration into mouse skin. This implies that NPe6 might be
      useful as a topical photosensitizer for PDT in treating skin cancers.

PMID- 14578581
TI  - Electrophysiological characterization of nicotine-induced excitation of
      dopaminergic neurons in the rat substantia nigra.
AB  - The electrophysiological characteristics of nicotine-induced excitation of
      dopaminergic neurons in the rat substantia nigra was investigated using the whole
      cell patch clamp technique under the voltage-clamp mode. Nicotine (0.01 - 100
      microM) induced inward currents corresponding to nicotine-induced depolarization
      with an increase in firing in a dose-dependent manner. This current was inhibited
      by dihydro-beta-erythroidine, a selective antagonist for the alpha4beta2 type
      neuronal nicotinic receptor. Nicotine directly acts on postsynaptic alpha4beta2
      type nicotinic receptors and induces inward currents, resulting in excitation of
      dopaminergic neurons in the substantia nigra and subsequent enhancement of
      dopamine release in the corpus striatum.

PMID- 14578582
TI  - Effect of dimethyl sulfoxide on excitation-contraction coupling in chicken slow
      skeletal muscle.
AB  - To evaluate the suitability of dimethyl sulfoxide (DMSO) as a solvent for muscle
      contraction studies in the chicken, its effect on the slow muscle contracture
      induced by high-K(+) solution was explored using the anterior latissimus dorsi
      (ALD) muscle from one-week-old chicks. Measurements were made of isometric
      tension and various characteristics of the contractures [peak tension, total
      tension (area under the curve), duration of contraction, drop in tension from
      peak to plateau, and resting tension], in the presence and absence of DMSO (20
      mM). Exposure to DMSO led to a concentration-dependent reduction in resting
      tension of up to 9 +/- 1.8% (n = 4) with respect to the control. The threshold
      concentration was 10 mM, and the maximum effect was reached between 20 and 30 mM.
      The drop in tension from peak to plateau was three times larger in the presence
      of DMSO (20 mM) than in its absence. At the same concentration, there was a 10 +/
      2.3% increase in the time constant of activation. No significant changes were
      observed in peak tension or in total tension in the presence of 20 mM DMSO. As a
      consequence, this type of biological preparation is not suitable for research on
      muscle contractures involving drugs that must be dissolved in DMSO (at the DMSO
      concentrations tested here).

PMID- 14578583
TI  - Pyrogens enhance beta-endorphin release in hypothalamus and trigger fever that
      can be attenuated by buprenorphine.
AB  - At first, we investigated whether both beta-endorphin release level in the
      hypothalamus and body temperature can be altered after intracerebroventricular
      (i.c.v.) injection of either lipopolysaccharide (LPS), interleukin-1beta (IL
      1beta), or prostaglandin E(2) (PGE(2)) in rats. It was found that in the rat,
      i.c.v. administration of either LPS (0.5 microg in 10 microl), IL-1beta (10 ng in
      10 microl), or PGE(2) (200 ng in 10 microl), in addition to producing fever,
      upregulated the immunoreactivity of beta-endorphin in the preoptic anterior
      hypothalamus of rat brain. Secondarily, we assessed whether the fever induced by
      either LPS, IL-1beta, or PGE(2) can be altered by pretreatment with buprenorphine
      (an opioid receptor antagonist). The results revealed that i.c.v. administration
      of buprenorphine (1 - 10 microg in 10 microl) alone had an insignificant effect
      on the body temperature. However, the fever induced by i.c.v. injection of either
      LPS, IL-1beta, or PGE(2) was significantly attenuated by pretreatment with i.c.v.
      injection of buprenorphine 1 h before the pyrogen injection in rats. The results
      suggest that pyrogens enhance beta-endorphin release in the hypothalamus and
      trigger fever which can be attenuated by buprenorphine, an opioid receptor
      antagonist.

PMID- 14578584
TI  - Protective effect of benidipine against sodium azide-induced cell death in
      cultured neonatal rat cardiac myocytes.
AB  - We investigated the effect of benidipine, a calcium antagonist, against sodium
      azide (NaN(3))-induced cell death in cultured neonatal rat cardiac myocytes with
      increase of LDH release, depletion of cellular ATP contents, and collapse of
      mitochondrial membrane potential (DeltaPsi) as indicators. Cells were treated
      with 1 mmol/L NaN(3) for 18 h. Benidipine concentration-dependently inhibited
      NaN(3)-induced cell death. The protective effect of benidipine was compared with
      those of amlodipine, nifedipine, candesartan, and captopril. Calcium antagonists
      exhibited a protective effect and the IC(50) values of benidipine, amlodipine,
      and nifedipine were 0.65, 90, and 65 nmol/L, respectively. NaN(3)-induced cell
      death was inhibited completely with the calpain inhibitor. It was considered that
      the sustained elevation of [Ca(2+)](i) might be implicated in NaN(3)-induced cell
      death. Benidipine, moreover, concentration-dependently preserved cellular ATP
      contents and maintained DeltaPsi the extent of the control level. In conclusion,
      benidipine exhibited the protective effect at an approximately 100-fold lower
      concentration than those of amlodipine and nifedipine in the NaN(3)-induced
      cardiac cell death model. It was considered that both the inhibition of Ca(2+)
      influx and the preservation of cellular ATP contents might play an important role
      in the protective effect of benidipine.

PMID- 14578585
TI  - Dependence of Ca2+-induced contraction on ATP in alpha-toxin-permeabilized
      preparations of rat femoral artery.
AB  - Effects of various concentrations of ATP on Ca(2+)-induced contraction were
      studied in alpha-toxin-permeabilized preparations obtained from the rat femoral
      artery. The contractile magnitude was highest in the presence of 1 mM ATP and
      decreased with both increasing and decreasing the concentration, suggesting the
      presence of an optimum ATP concentration in inducing contraction. The magnitude
      of the contractions in various concentrations of ATP correlated with the extent
      of the phosphorylated myosin light chain (MLC). The rate of contractions in the
      presence of 1 mM ATP under an inhibition of MLC phosphatase was faster than in
      the presence of 4 mM ATP, suggesting that the increased phosphorylation of MLC at
      1 mM ATP results from an increased activity of MLC kinase. On the other hand, MLC
      phosphatase activity appeared unchanged, because the rates of relaxations under
      the inhibition of MLC kinase were not different in the presence of either 1 or 4
      mM ATP. The high sensitivity to 1 mM ATP was absent in the preparations that were
      permeabilized with beta-escin or Triton X-100, suggesting the existence of an
      intracellular factor required for the increased activity of MLC kinase to ATP in
      the alpha-toxin-permeabilized preparations of the rat femoral artery.

PMID- 14578586
TI  - Epibatidine induces long-term potentiation (LTP) via activation of alpha4beta2
      nicotinic acetylcholine receptors (nAChRs) in vivo in the intact mouse dentate
      gyrus: both alpha7 and alpha4beta2 nAChRs essential to nicotinic LTP.
AB  - Activation of nicotinic acetylcholine receptors (nAChRs) induces nocotinic long
      term potentiation (LTPn) in vivo in the mouse dentate gyrus. We have found that
      alpha4beta2 nAChRs activated by epibatidine induce LTPn, the full size of which
      requires the involvement of alpha4beta2 and alpha7 nAChRs, in the intact mouse
      dentate gyrus using extracellular recording techniques. Intraperitoneal
      application of epibatidine, a potent alpha4beta2 nAChR agonist, at 0.3 - 3.0
      mug/kg induced a long-lasting increase similar to LTPn induced by choline, a
      selective alpha7 nAChR agonist, and at 10 mug/kg caused a transient increase
      followed by a depression. The LTPn induced by epibatidine at 3.0 mug/kg or
      choline at 30 mg/kg was significantly suppressed by pre-treatment but not post
      treatment with mecamylamine (0.5 mg/kg, i.p.), a non-selective neuronal nicotinic
      antagonist. Post-application of nicotine at 3.0 mg/kg enhanced epibatidine
      induced LTPn to the same level of nicotine-induced LTPn, but post-application of
      epibatidine had no effect on nicotine-induced LTPn. Epibatidine-induced LTPn was
      additionally increased by post-application of choline, and vice versa, reaching
      the same level of nicotine-induced LTPn. The present study revealed that
      epibatidine induced the LTPn via alpha4beta2 nAChRs and that both alpha7 and
      alpha4beta2 nAChRs were essential for full-sized LTPn, suggesting that both
      nAChRs play an important role in synaptic plasticity.

PMID- 14578587
TI  - Effect of nilvadipine on the cerebral ischemia-induced impairment of spatial
      memory and hippocampal apoptosis in rats.
AB  - We investigated the effects of nilvadipine and amlodipine on the cerebral
      ischemia-induced impairment of spatial memory in 8-arm radial maze performance
      and hippocampal CA1 apoptosis in rats. Single cerebral ischemia impaired memory
      without inducing apoptosis. In these rats, neither nilvadipine nor amlodipine at
      3.2 mg/kg, i.p. improved the impaired memory. On the other hand, repeated
      cerebral ischemia (10 min ischemia x 2, 1 h interval) impaired spatial memory and
      induced hippocampal apoptosis 7 days after the final occlusion/reperfusion.
      Moreover, repeated ischemia increased the apoptotic cell number, an effect
      observed after 3 days and peaked after 7 days. However, mRNA expression of the
      apoptosis-related early oncogene bax and CPP 32 (caspase-3) was observed after 24
      h. In these rats, nilvadipine, but not amlodipine, significantly improved memory,
      concomitantly decreased hippocampal apoptosis, and suppressed both bax and CPP 32
      expression. These results suggest that nilvadipine improved the memory impairment
      in repeated ischemia by reducing bax and CPP 32 expression and suppressing the
      induction of apoptosis in the hippocampus. Nilvadipine may have a neuroprotective
      effect and could be a useful pharmacotherapeutic agent for cerebrovascular
      dementia.

PMID- 14578588
TI  - Taxol inhibits melanoma metastases through apoptosis induction, angiogenesis
      inhibition, and restoration of E-cadherin and nm23 expression.
AB  - An in vivo melanoma spontaneous metastases model was adopted to study the
      molecular mechanisms of the anti-metastatic effect of Taxol. The morphology of
      melanoma cells in the melanoma tissue lesions was examined by hematoxylin/eosin
      (H&E) staining and electron microscopy. The in situ programmed cell death was
      tested by TUNEL analysis. Vascular endothelial growth factor (VEGF) and E
      cadherin expression were detected by immunohistochemistry. The metastases
      suppressor gene nm23 mRNA expression level was analyzed by in situ hybridization.
      The results showed that i.p. injection of Taxol at 5 mg/kg per day for three
      weeks significantly inhibited metastases formation in the pulmonary of mice.
      Taxol induced melanogenesis and apoptosis in the melanoma cells, inhibited
      angiogenesis in melanoma tissue lesions, and reduced the expression of VEGF.
      Conversely, Taxol increased the expression of E-cadherin and nm23. In conclusion,
      administration of Taxol in the early stage of melanoma metastases can
      significantly inhibit melanoma metastases. This effect was possibly related to
      apoptosis induction, tumor angiogenesis inhibition, and restoration of the
      metastasis suppression ability.

PMID- 14578589
TI  - Effect of zaleplon, a non-benzodiazepine hypnotic, on melatonin secretion in
      rabbits.
AB  - Melatonin, a major hormone secreted by the pineal gland, is known to play an
      important role in regulation of the circadian rhythm. (N-[3-(3-cyanopyrazolo[1,5
      a]pyrimidin-7-yl)phenyl]-N-ethylacetamide (zaleplon) is a non-benzodiazepine
      hypnotic that acts via the benzodiazepine site of the GABA(A) receptor. In the
      present study, we investigated the effect of zaleplon on melatonin secretion in
      rabbits using RIA and compared the effect to triazolam and zopiclone. Zaleplon
      increased a dose-dependent concentration of melatonin in rabbit plasma collected
      at 30 min after intravenous administration at doses of 1 and 2 mg/kg. The
      zaleplon-induced increase in plasma melatonin level was not blocked by
      flumazenil, a benzodiazepine-receptor antagonist. In contrast, triazolam and
      zopiclone failed to affect the plasma melatonin level. We also investigated the
      effect of zaleplon on intracellular cAMP in rat pinealocytes. Consequently,
      zaleplon had no effect on the intracellular cAMP levels in rat pinealocytes.
      These results of the present studies suggest that zaleplon may promote melatonin
      secretion and the elevation of plasma levels of melatonin may suggest an
      influence of zaleplon on chronobiology.

PMID- 14578590
TI  - Effect of volatile anesthetics on steroidogenesis in isolated bovine
      adrenocortical fasciculata cells.
AB  - To examine effects of volatile anesthetics (VAs) on steroidogenesis, cell
      suspensions of isolated bovine adrenocortical cells were incubated with several
      steroidogenic agents in the presence or absence of halothane and sevoflurane. The
      adrenocortical cells were dispersed by trypsin digestion of bovine adrenal
      cortex. The cortisol level was measured fluorometrically. VAs inhibited
      adrenocorticotropic hormone-, acetylcholine-, angiotensin-II-, and KCl-stimulated
      steroidogenesis in a concentration-dependent manner with extracellular Ca(2+).
      However, dibutyryl cyclic adenosine monophosphate-stimulated steroidogenesis was
      not inhibited by VAs. These results suggest that VAs inhibit steroidogenesis by
      blocking Ca(2+)-influx from the extracellular space without influencing the
      action of intracellular cyclic nucleotides.

PMID- 14578591
TI  - RNA interference with small hairpin RNAs transcribed from a human U6 promoter
      driven DNA vector.
AB  - RNA interference (RNAi), a process of sequence-specific gene suppression, has
      been known as a natural gene regulatory mechanism in a wide range of organisms.
      Recently, a small-interference RNA (siRNA) technology has been reported to
      produce post-transcriptional gene silencing in mammalian cells. In the present
      study, we constructed a human U6 promoter-driven mammalian expression vector to
      produce hairpin double-stranded RNA and transfected this into a human cell line.
      Using this siRNA system, we were able to knock down the gene expression of an
      enhanced green fluorescence protein. This result indicates that the plasmid
      vector-based siRNA system is a promising method to downregulate gene expression
      in human cells.

PMID- 14578592
TI  - Red ginseng inhibits exercise-induced increase in 5-hydroxytryptamine synthesis
      and tryptophan hydroxylase expression in dorsal raphe of rats.
AB  - Red ginseng has been used as an ergogenic aid for endurance exercise. In this
      study, the effect of aqueous extract of Red ginseng on the endurance in treadmill
      exercise and 5-hydroxytryptamine (serotonin) synthesis and tryptophan hydroxylase
      expression in the dorsal raphe of rats were studied. Rats receiving Red ginseng
      showed increased time to exhaustion for treadmill running, and Red ginseng
      treatment inhibited exercise-induced increases in 5-hydroxytryptamine synthesis
      and tryptophan hydroxylase expression in the dorsal raphe. These results suggest
      that the suppressive effect of Red ginseng on serotonin level during exercise is
      a possible ergogenic mechanism of Red ginseng.

PMID- 14578593
TI  - A novel in vitro model for screening and evaluation of anti-asthenopia drugs.
AB  - Patients suffering asthenopia are steadily increasing with an expanding use of
      visual display terminals such as computers. An attempt was made to develop an in
      vitro model for asthenopia. Ciliary muscle removed from eyeballs of a rabbit was
      stimulated with acethylcholine, resulting in contraction of the muscle. Repeated
      stimulations caused decreased contraction, which may be related to fatiguing of
      ciliary muscle and hence asthenopia. Treatment of the repeatedly stimulated
      muscle with cyanocobalamin restored contraction dose-dependently. Thus, the model
      developed in this study can be used to screen drug candidates for treating
      asthenopia.

PMID- 14578594
TI  - Current characteristics of infective endocarditis in Japan: an analysis of 848
      cases in 2000 and 2001.
AB  - The Japanese Circulation Society appointed a committee to develop guidelines for
      the prevention, diagnosis and management of infective endocarditis in Japan. In
      making such guidelines, the committee required information on the current
      clinical characteristics of infective endocarditis and therefore performed a
      nationwide questionnaire survey of cases from 2000 and 2001. In total, data were
      received for 848 cases from 277 of the 817 hospitals surveyed. Mean age was 55+/
      18 years and most patients were aged in their 50 s or 60 s; 53.9% of the patients
      had infective endocarditis of unknown origin (without any prior predisposing
      conditions or procedures) and the second most common etiology was post dental
      procedures. The most common microorganism was Gram-positive cocci (345
      streptococci and 221 staphylococci) and methicillin resistant Staphylococcus
      aureus (MRSA) was found in 7.3%. Although more than 90% of cases with
      Streptococcus viridans were sensitive to penicillin G, 6.6% were resistant. All
      MRSAs were sensitive to vancomycin. The information obtained from the survey
      assisted in the making of the guidelines, which should become an indispensable
      tool for all clinicians.

PMID- 14578595
TI  - Right ventricle to pulmonary artery reconstruction using a valved homograft.
AB  - Although the valved homograft is widely used to establish a connection between
      the right ventricle (RV) and the pulmonary artery (PA), its durability remains
      controversial. In the present study, the data on 141 valved homograft
      implantations in 107 consecutive patients performed from January 1990 to June
      2000 were analyzed. The mean follow-up period was 4.6 years (range, 0.2-9.4
      years). The clinical data, including clinic records, operative notes, follow-up
      visits, and letters from referring physicians, were analyzed with particular
      reference to variables associated with early and late mortality, deterioration of
      the homograft, and risk factors for patient survival and homograft failure. Early
      death occurred in 7.5% (n=8) of the cases, and each of these patients died
      without leaving the hospital. Late death occurred in 2 patients, for whom the
      cause of death was suggested to be related to arrhythmia. Thirteen patients
      underwent catheter intervention (ie, balloon dilatation and/or stenting) and 8 of
      these did not require homograft replacement following catheterization. The
      overall survival rate at both 3 years and 5 years was 88.9+/-3.4%. Cumulative
      freedom from total homograft failure was 82.5+/-3.6% at 1 year; 61.6+/-5.0% at 3
      years; and 42.4+/-6.2% at 5 years. In comparison with 2 criteria of homograft
      failure (ie, total homograft failure and homograft failure including catheter
      intervention), the incidence of freedom from homograft failure including catheter
      intervention was lower than that of total homograft failure, although the
      difference was not statistically significant. In the multivariate analysis,
      significant risk factors with respect to patient survival were homograft
      replacement and the use of expanded polytetrafluoroethylene (ePTFE); those judged
      to be significant with respect to homograft failure were total repair with first
      homograft implantation and diagnosis of truncus arteriosus. The valved homograft
      was thus considered an appropriate choice of conduit between the RV and the PA,
      and it provided excellent patient survival. However, this type of homograft did
      not provide a completely permanent solution for the repair of complex cardiac
      anomalies. Therefore, the use of ePTFE for homograft extensions should be
      avoided. Finally, the results suggest that catheter intervention plays an
      important role in the longevity of the implanted homograft.

PMID- 14578596
TI  - Medium- to long-term prognostic impact of dipyridamole thallum-201 myocardial
      single-photon emission computed tomography in elderly patients.
AB  - Dipyridamole thallium-201 single-photon emission computed tomography (SPECT) has
      not been extensively evaluated for risk stratification and the medium- to long
      term prognostic value in elderly cardiac patients who are unable to exercise. The
      present study group comprised 210 consecutive patients aged at least 70 years
      with known or suspected coronary artery disease (CAD). The SPECT findings were
      classified as a reversible, fixed, or combined (reversible and fixed) defect. Of
      the 210 patients, 201 (77+/-5 years, 85 male) were successfully followed for 49+/
      26 months. Thirteen (7%) patients had cardiac events: cardiac death (n=10), non
      fatal myocardial infarction (n=1), or coronary artery bypass grafting (n=2).
      Cardiac events occurred in 3 of 112 patients with normal SPECT and in 10 of 89
      patients with an abnormal scan (0.7% /year vs 2.8% /year, p=0.01). Stepwise Cox
      regression analysis revealed that the significant predictors of cardiac events
      were combined defects (relative risk 7.3) and the number of defect areas
      (relative risk 4.4). The predictive value of dipyridamole thallium-201 SPECT is
      maintained over 4 years in mixed populations of elderly CAD patients who are
      unable to exercise.

PMID- 14578597
TI  - Clinical value of iodine-123 beta-methyliodophenyl pentadecanoic acid (BMIPP)
      myocardial single photon emission computed tomography for predicting cardiac
      death among patients with chronic heart failure.
AB  - In the present study, the effectiveness of 123I-beta-methyliodophenyl
      pentadecanoic acid (BMIPP) single photon emission computed tomography (SPECT) for
      predicting cardiac death of patients with chronic heart failure was evaluated.
      Abnormalities of fatty acid metabolism are found in patients with chronic heart
      failure and BMIPP was developed as a tracer for scintigraphic assessment of
      myocardial fatty acid utilization. The study group comprised 74 patients with
      chronic heart failure with a left ventricular ejection fraction (LVEF) <45% on
      left ventriculography or radionuclide angiocardiography. They underwent both
      201Tl SPECT and BMIPP SPECT. The uptake of tracer was scored semiquantitatively
      from 0 (normal) to 4 (defect) in 20 segments and a total defect score (TDS) for
      all 20 segments was calculated. On planar images the mediastinum to heart count
      ratio (H/M) was calculated for the BMIPP and Tl studies, and the
      H/M(BMIPP):H/M(Tl) (H/M(BMIPP) divided by H/M(Tl)) was also calculated. The mean
      follow-up period was 660 days and there were 17 cases of cardiac death.
      Multivariate analysis identified H/M(BMIPP):H/M(Tl) (p<0.05) and LVEF (p<0.05) as
      independent predictors of cardiac death. The receiver-operating characteristic
      curve of H/M(BMIPP):H/M (Tl) was situated to the left relative to LVEF. Analysis
      of the myocardial metabolism by BMIPP SPECT can predict the high-risk patients
      with chronic heart failure.

PMID- 14578598
TI  - Arrhythmogenic right ventricular cardiomyopathy and sudden cardiac death in young
      Koreans.
AB  - The aim of this study was to assess the frequency and clinical characteristics of
      arrhythmogenic right ventricular cardiomyopathy (ARVC) in young victims of sudden
      cardiac death (SCD). From January 1999 to December 2000, postmortem studies were
      conducted in 38 cases of SCD (age < or =35 (27+/-7) years old, 26 male) from the
      Taegu-Kyungpook region of southeastern Korea. Cases of sudden infant death
      syndrome were excluded. The causes of SCD were ARVC in 42%, acute myocardial
      infarction in 11%, myocarditis in 11%, pulmonary embolism in 8%, hypertrophic
      cardiomyopathy in 5%, aortic rupture in 3%, aortic stenosis in 3%, and unknown in
      18%. The mean age of the 16 ARVC victims was 27+/-5 years and 10 were male. None
      were competitive athletes, or had been suspected of having cardiovascular disease
      before death. SCD was not related to vigorous physical or competitive activity
      and occurred during sleep in 7 cases, during work in 4, during bathing in 2,
      while driving, praying and eating in 1 case each. ARVC is an important cause of
      SCD in young people in this area of Korea.

PMID- 14578599
TI  - Early detection of doxorubicin-induced myocardial damage by ultrasound tissue
      characterization with integrated backscatter.
AB  - Doxorubicin (DXR) is one of the most effective antineoplastic agents, but its use
      is limited by its myocardial toxicity. Myocardial injury reduces the cyclic
      variation of integrated backscatter (CV-IBS) and so the present study was
      designed to investigate whether CV-IBS can be used to detect the early phase of
      myocardial damage in patients receiving DXR. Thirty-four subjects constituted the
      study population, none of whom showed clinically evident heart failure. CV-IBS
      was obtained for both the interventricular septum and the left ventricular
      posterior wall in the parasternal short-axis view. Standard echographic measures
      of left ventricular function were also made. Subjects without DXR exposure or
      evident cardiac diseases served as controls. The total dose of DXR administered
      per patient was 339+/-164 mg/m2 (range: 95-680 mg/m2). Conventional echographic
      parameters, including left ventricular wall thickness, dimensions, fractional
      shortening, and ejection fraction, showed no significant differences between the
      2 groups. In contrast, CV-IBS was significantly decreased in the DXR group
      compared with the control group (septum: 4.7+/-1.7 vs 7.2+/-1.9 dB, p<0.0001;
      posterior wall: 6.7 +/-2.2 vs 8.0+/-1.6 dB, p<0.05). CV-IBS can be used as an
      early indicator of DXR-induced myocardial damage in patients demonstrating normal
      left ventricular systolic function.

PMID- 14578600
TI  - Clinical characteristics of Brugada syndrome in a Korean population.
AB  - The objective of this study was to investigate the clinical features of Korean
      patients with Brugada syndrome (BS). Between June 1998 and April 2002, 15
      consecutive patients with BS (13 men, 2 women; mean age, 44+/-10 years) were
      identified. Eight patients had experienced at least 1 episode of aborted sudden
      death, 5 patients had had an episode of syncope or chest pain, and 2 patients
      were asymptomatic at diagnosis. The electrocardiographics (ECGs) of all patients
      showed spontaneous ST-segment elevation in leads V(1-3) at baseline and 13
      patients (87%) showed transient normalization of the ST-segment elevation during
      follow-up. Twelve patients received an implantable cardioverter-defibrillator (6
      patients with aborted sudden death, 5 patients with syncope or chest pain, 1
      asymptomatic patient). During a mean follow-up of 19+/-14 months, arrhythmic
      events occurred in 5 of the 6 patients with aborted sudden death and in 1 of the
      5 patients with syncope or chest pain. None of the asymptomatic patients
      developed any symptoms suggestive of an arrhythmic event. The clinical and ECG
      manifestation of BS in Korean patients is diverse, but the dynamic nature of the
      ST segment provides an important clue to the diagnosis of BS. Recurrence of
      malignant arrhythmia is extremely high in those patients who initially present
      with aborted sudden death.

PMID- 14578601
TI  - Identification of functional block line in atrial flutter using three-dimensional
      intracardiac echocardiography.
AB  - The crista terminalis (CT) is reportedly a critical barrier for maintaining
      typical atrial flutter (AFL), but recent observations have suggested the presence
      of posteromedial functional block, as well as crista conduction. Therefore, this
      study was designed to identify the correlation between the posterior boundary of
      AFL and anatomical architecture in the human right atrium (RA) using 3
      dimensional (D) intracardiac echocardiography (ICE). In 11 patients with AFL
      (typical 9, reverse typical 2), mapping with a 10-pole (n=5) or 32-pole (n=6)
      catheter was performed during AFL. ICE was used to determine the catheter's
      position relative to the intra-atrial structures. In all patients, double
      potentials were recorded at the posteromedial RA and the catheter positions were
      recognized as posterior to the CT by 3-D ICE. Double potentials were not recorded
      on the CT, and the activation sequence revealed a craniocaudal direction in the 9
      patients with typical AFL and caudocranial direction in the 2 patients with
      reverse typical AFL. These findings demonstrate that the posterior boundary of
      the AFL circuit is in the sinus venosa region posterior to the CT, which may
      provide an important insight into the mechanism of maintaining AFL.

PMID- 14578602
TI  - Optimum hypoglycemic therapy can improve coronary flow velocity reserve in
      diabetic patients: demonstration by transthoracic doppler echocardiography.
AB  - The purpose of this study was to determine whether the elimination or the
      alleviation of hyperglycemia would improve coronary flow velocity reserve (CFVR)
      using transthoracic Doppler echocardiography (TTDE). CFVR was measured by TTDE in
      the left anterior descending coronary artery in 49 poorly controlled diabetic
      patients before and after antidiabetic treatment and 15 well controlled diabetic
      patients also underwent the same measurements. The fasting blood glucose level in
      the poorly controlled patients reduced from 270 +/-106 mg/dl to 116+/-39 mg/dl at
      20+/-15 days after the intensive treatment. Although baseline coronary flow
      velocity (CFV) did not change between the 2 measurements (19.9+/-6.9 cm/s vs
      19.0+/-5.4 cm/s, p=NS), the hyperemic CFV increased significantly after the
      treatment (47.3+/-13.4 cm/s vs 55.4+/-13.2 cm/s, p<0.001). Thus, the CFVR
      improved significantly after the treatment (2.47+/-0.55 vs 2.98+/-0.56, p<0.001).
      Although there was minimal improvement in the control group (2.37+/-0.38 vs
      2.50+/-0.37, p<0.05), the improvement in CFVR was significantly greater in the
      poorly controlled patients with intensive treatment (0.51+/-0.33 vs 0.12+/-0.19,
      p<0.001) than that in the control group. These results suggest that optimal
      hypoglycemic therapy is important to improve the CFVR in poorly controlled
      diabetic patients.

PMID- 14578603
TI  - Effectiveness of thrombectomy before stent implantation in acute myocardial
      infarction.
AB  - Percutaneous coronary intervention (PCI) in patients with acute myocardial
      infarction (AMI) may cause distal embolization, with deterioration of distal flow
      and further extension of the infarct. The purpose of the present study was to
      evaluate the effectiveness of pretreatment by thrombectomy on myocardial salvage
      after stent implantation in patients with AMI. From January 2000 to July 2002,
      209 consecutive patients with AMI successfully underwent emergency stent
      implantation. They were divided into 2 groups: those treated in the year before
      the introduction of the thrombectomy device (Group A; n=109), and those treated
      the year after introduction of the device (Group B; n=100). Follow-up
      quantitative coronary angiography (QCA) and left ventriculography were carried
      out 6 months after PCI. Microvascular circulation after revascularization was
      assessed by Thrombolysis in myocardial infarction (TIMI) flow grade analysis, the
      maximum creatine kinase concentration was recorded, and the follow-up left
      ventricular ejection fraction and ST segment score were assessed on the 12-lead
      electrocardiography just before revascularization and on return to the coronary
      care unit. The QCA data, rate of restenosis (% restenosis) and rate of target
      lesion revascularization were also compared between the 2 groups. The results
      demonstrated that the introduction of thrombectomy had increased the number of
      patients who displayed blush-3 after primary angioplasty, which suggests that
      thrombectomy before stent implantation has the potential to minimize myocardial
      ischemic insult, presumably by protecting the coronary microvasculature.

PMID- 14578604
TI  - Ischemia-induced translocation of protein kinase C-epsilon mediates
      cardioprotection in the streptozotocin-induced diabetic rat.
AB  - The present study investigated the role of translocation of protein kinase C
      (PKC) during ischemia/reperfusion in cardioprotection in the streptozotocin (STZ)
      induced diabetic rat. Twelve weeks after injection of STZ or vehicle, male Wister
      King rat hearts were isolated and perfused in the presence or absence of 50
      nmol/L staurosporine or 2 mumol/L chelerythrine using a Langendorff apparatus.
      Thirty minutes of global ischemia was followed by the same period of reperfusion.
      The time to onset of contracture was determined during ischemia. The recovery of
      left ventricular function, incidence of ventricular tachycardia/fibrillation
      (VT/VF), and amount of released creatine kinase (CK) were determined during the
      reperfusion period. Translocation of the PKC-alpha, -beta, -delta and -epsilon
      isoforms was determined by immunoblotting. Development of contracture was
      delayed, the recovery of left ventricular function was greater, and the incidence
      of VT/VF and amount of released CK were lower in diabetic than in control hearts.
      Ischemia caused an increase in the particulate/cytosolic fraction ratio of the
      PKC- epsilon isoform in the diabetic and control hearts. However, this
      translocation of PKC-epsilon during ischemia was transient in the control heart,
      but was persistent in the diabetic heart. The ischemia-induced translocation of
      PKC-epsilon was abolished by chelerythrine perfusion. These results suggest that
      persistent translocation of PKC-epsilon during ischemia plays a major role in
      cardioprotection against ischemia/reperfusion injury in STZ-induced diabetic
      rats.

PMID- 14578605
TI  - Subepicardial aneurysm associated with ventricular septal perforation showing a
      normal coronary angiogram.
AB  - Subepicardial aneurysm is a rare complication of acute myocardial infarction and
      the present case was associated with ventricular septal perforation.
      Echocardiography showed the subepicardial aneurysm adjoining the true apico
      anteroseptal aneurysm, with the former being discontinuous with the myocardium at
      its neck, which was narrower than the diameter of the aneurysm. In addition,
      color Doppler imaging showed shunt flow from the aneurysm to the right ventricle.
      Coronary angiography revealed extension only of the anterior descending artery
      without any discernible stenosis. The apical aneurysm was excised and the defect
      closed with an epicardial patch. The myocardial infarction was probably caused by
      coronary spasm. Echocardiography was useful for diagnosing the anatomy and
      hemodynamic condition of the subepicardial aneurysm.

PMID- 14578606
TI  - Cardiac amyloidosis associated with a novel transthyretin aspartic acid-18
      glutamic acid de novo mutation.
AB  - A 40-year-old man presented with initial symptoms of syncope caused by
      restrictive cardiomyopathy and autonomic nervous system impairment, but it was
      confirmed that he had a novel transthyretin (TTR) variant, aspartic acid-18
      glutamic acid (Glu), and a de novo gene mutation. A polymerase chain reaction
      induced mutation restriction analysis with a mismatched sense primer demonstrated
      that he was heterozygous for TTR Glu 18. Liver transplantation was not performed
      because of profound weakness and severe postural hypotension. Right-sided heart
      failure predominated in association with low output syndrome and a gradual
      decrease in total QRS voltage on electrocardiogram over 5 years of follow-up.
      Autonomic neuropathy developed and he eventually died of both-sided heart failure
      at the age of 45 years. Immunohistochemical and DNA studies are important to
      diagnose and treat TTR-related cardiac amyloidosis.

PMID- 14578607
TI  - Restrictive cardiomyopathy with right-sided dominant heart failure after sinus
      conversion from atrial fibrillation: case report.
AB  - A 44-year-old woman with restrictive cardiomyopathy showed right-sided dominant
      heart failure after conversion to sinus rhythm from paroxysmal atrial
      fibrillation (AF). During cardiac catheterization, the hemodynamics were compared
      before and after cardioversion; that is, with AF and with sinus rhythm. The
      hemodynamic parameters worsened after conversion to sinus rhythm, with a
      significant decrease in heart rate, but improved with atrial pacing. Pacemaker
      implantation was performed to avoid bradycardia while keeping the sinus rhythm
      with amiodarone. As a result, the patient has been free from symptoms of heart
      failure for almost 1 year and her serum brain natriuretic peptide level also
      improved remarkably.

PMID- 14578608
TI  - Multiple left ventricular diverticula detected by second harmonic imaging: a case
      report.
AB  - A 51-year-old Japanese man was admitted to hospital for evaluation of anterior
      chest pain at rest. He had a past history of cerebellar infarction when he was 47
      years old. A conventional 2-dimensional echocardiogram revealed normal left
      ventricular function, and no abnormal findings. However, second harmonic imaging
      demonstrated 2 noncontractile diverticula at the submitral annular portion of the
      posterior wall of the left ventricle. Second harmonic imaging revealed another
      contractile diverticulum at the anterior wall of left ventricle in the short-axis
      view. These findings were confirmed by left ventriculography. After confirming
      the diagnosis of multiple left ventricular diverticula, a rare type of congenital
      anomaly, anticoagulant therapy was started and he is well to date. Left
      ventricular diverticula are clinically very important because they are often
      associated with serious complications such as systemic thromboembolism.
      Enhancement of the left ventricular endocardial borders by second harmonic
      imaging is useful for the diagnosis of left ventricular diverticula.

PMID- 14578609
TI  - Mikamo Lecture: a radical view on the 'superfamily' of cardiovascular risk
      factors.
AB  - Many risk factors for cardiovascular disease generate superoxide in the blood
      vessels and thereby impair endothelial function. To emphasize the critical role
      of oxygen radicals, this is a 'radical view' of those risk factors. It will be
      useful to organize risk factors into a 'superfamily', with consideration of
      mediators, mechanisms, and target organs. Studies are summarized which suggest
      that, in parallel with the impairment of endothelial vasomotor function, the
      thrombin/thrombomodulin/activated protein C anticoagulant mechanism, which
      requires endothelial thrombomodulin, is also impaired by atherosclerosis and
      improves during regression of atherosclerosis. Impairment of the anticoagulant
      mechanism may contribute to thrombosis in atherosclerotic arteries, and
      improvement of the anticoagulant mechanism during regression of atherosclerosis
      may reduce the risk of cardiovascular events.

PMID- 14578610
TI  - Decrease in the spatial dispersion at the termination of atrial fibrillation by
      intravenous cibenzoline.
AB  - Atrial electrograms were recorded from the high right atrium, coronary sinus, and
      right lateral wall in 15 patients with induced atrial fibrillation (AF).
      Intravenous cibenzoline terminated AF in 8 patients (T group), but not in 7
      patients (non-T group). The cycle length of the AF (AFCL) obtained by the
      autocorrelation function was measured every 5 s during the 30 s prior to the
      cibenzoline administration, and just before the termination of AF or at the end
      of the cibenzoline infusion in the non-T group. The mean AFCL, and spatial and
      temporal dispersion of the AFCL were then compared between the 2 groups
      (dispersion = standard deviation x 100 /mean AFCL). Cibenzoline significantly
      increased the mean AFCL and decreased the spatial dispersion in both groups. No
      significant difference in either the mean AFCL or temporal dispersion before or
      after cibenzoline was observed between the 2 groups. In addition, no significant
      difference in the spatial dispersion before the cibenzoline was observed, but the
      spatial dispersion after the cibenzoline was significantly smaller in the T group
      than in the non-T group. The mean AFCL, and the spatial and temporal dispersion
      before the cibenzoline did not predict the termination of AF. The decrease in the
      spatial dispersion may be the most important mechanism by which intravenous
      cibenzoline terminates AF.

PMID- 14578611
TI  - Effects of atorvastatin and pravastatin on malondialdehyde-modified LDL in
      hypercholesterolemic patients.
AB  - The aim of the present study was to compare the effects of atorvastatin and
      pravastatin on lipid parameters and the concentration of malondialdehyde-modified
      low-density lipoprotein (MDA-LDL) in hypercholesterolemic patients. A total of 17
      patients (10 men, 7 women; mean age, 68+/-9 years) who were indicated for drug
      therapy based on the National Cholesterol Education Program II underwent an 8
      week regimen of atorvastatin (10 mg/day) or pravastatin (10 mg/day) with a 4-week
      washout period between drugs. After an overnight fast, lipid parameters and MDA
      LDL concentration were measured before and after the 8-week treatment with each
      drug. Both atorvastatin and pravastatin produced significant reductions in low
      density lipoprotein (LDL) cholesterol and MDA-LDL concentrations, with a
      significant increase in high-density lipoprotein cholesterol concentration. The
      percent reductions in LDL cholesterol and MDA-LDL concentration were
      significantly greater with atorvastatin than pravastatin (46 +/-6% vs 24+/-10%,
      p<0.0001, and 44+/-10% vs 14+/-13%, p<0.0001, respectively). The ratios of
      percent reductions in MDA-LDL concentrations and percent reductions in LDL
      cholesterol concentrations were significantly greater for atorvastatin than
      pravastatin (0.96+/-0.19 vs 0.59+/-0.55, p<0.0001). In conclusion, atorvastatin
      reduced serum concentrations of LDL cholesterol and MDA-LDL to a greater degree
      than pravastatin, indicating that atorvastatin not only has stronger lipid
      lowering effects, but also stronger antioxidative effects than pravastatin.

PMID- 14578612
TI  - Effect of long-term beta-blocker therapy on microvolt-level T-wave alternans in
      association with the improvement of the cardiac sympathetic nervous system and
      systolic function in patients with non-ischemic heart disease.
AB  - The purpose of this study was to test a hypothesis that T-wave alternans (TWA) is
      improved in association with an improvement in cardiac sympathetic nervous system
      and systolic function by oral beta-blocker therapy in patients with non-ischemic
      heart disease (NIHD). TWA testing, (123)I-metaiodobenzylguanidine (MIBG) imaging
      and echocardiography were performed at the baseline and 3 months after beta
      blocker therapy in 26 patients with NIHD and positive TWA. The alternans voltage
      (V(alt)), the heart-to mediastinal-ratio on the early (e-H/M) and delayed (d-H/M)
      images, the washout rate (WR), the left ventricular ejection fraction (LVEF), and
      the calculated rate of change by beta-blocker therapy in each parameter (ie,
      deltaV(alt), deltae-H/M, deltad-H/M, deltaWR and deltaLVEF) were measured. After
      therapy, TWA turned negative in 8 patients (group A) and remained positive in 18
      (group B); V(alt) was significantly decreased in group B (p<0.001). In group A, e
      H/M, d-H/M and LVEF were significantly increased (e-H/M: p<0.05, d-H/M and LVEF:
      p<0.01), as were e-H/M and LVEF in group B (p<0.05). There were significant
      correlations between deltaV(alt) and deltae-H/M (r=-0.61, p<0.01), deltad-H/M (r=
      0.82, p<0.0001), deltaWR (r=0.60, p<0.01) and deltaLVEF (r=-0.70, p<0.01). In
      patients with NIHD, the TWA is improved in association with the improvement in
      cardiac sympathetic nervous system abnormalities and left ventricular systolic
      dysfunction by beta-blocker therapy.

PMID- 14578613
TI  - Effect of beta-blocker therapy in elderly patients with dilated cardiomyopathy.
AB  - The aim of this study was to evaluate whether beta-blocker therapy can be safely
      administered to and improve cardiac function of elderly patients with dilated
      cardiomyopathy (DCM). Echocardiography and measurement of the concentrations of
      natriuretic peptides were carried out in 67 patients with DCM before and after 6
      months of beta-blocker therapy: 20 patients >/=65 years of age (older group); 47
      <65 years of age (younger group). In all patients, beta-blocker was safely
      administered and well tolerated. There was no significant difference in the dose
      of beta-blocker between 2 groups. A reduction in the left ventricular dimensions
      and an associated increase in ejection fraction occurred in both treatment
      groups. The beta-blocker treatment resulted in a significant decrease in the
      concentrations of natriuretic peptides in both groups. In conclusion, beta
      blocker therapy is well-tolerated and has similar effects on cardiac function in
      older and younger patients with DCM.

PMID- 14578614
TI  - Reverse redistribution phenomenon on rest (99m)Tc-tetrofosmin myocardial single
      photon emission computed tomography involves impaired left ventricular
      contraction in patients with acute myocardial infarction.
AB  - The purpose of this study was to investigate the clinical significance of the
      reverse redistribution (RR) phenomenon on technetium-99m ((99m)Tc)-tetrofosmin
      myocardial single photon emission computed tomography (SPECT) performed at rest.
      Twenty-five patients underwent myocardial SPECT 3 weeks after the onset of acute
      myocardial infarction. Myocardial images were acquired at 40 min (early) and 4 h
      (delayed) after the injection of 740 MBq of (99m)Tc-tetrofosmin. The regional
      myocardial uptake of the tracer in 26 segments of the left ventricular (LV) wall
      was visually scored from 0 (no activity) to 3 (normal activity), and then the RR
      was defined as a decrease of more than 1 point in the activity score on the
      delayed image compared with that on the early image. Regions with an activity
      score of 3 on both the early and delayed images were defined as normal, and those
      with a score of 0 or 1 on the early image were considered to have a fixed defect.
      The regional myocardial (99m)Tc-tetrofosmin uptake and washout rate were also
      quantitatively assessed in each region. In addition, exercise stress
      electrocardiograph-gated SPECT with (99m)Tc-tetrofosmin was performed within 1
      week of the rest study, and the percent count increase (%CI) during myocardial
      contraction in each corresponding region was studied. RR was observed in 18 of
      the 25 patients. The regional washout rate of (99m)Tc-tetrofosmin was
      significantly higher in the RR regions (45.0+/-3.8%) than in either the normal
      regions (36.4+/-4.1%, p<0.001) or in those with a fixed defect (39.7+/-3.9%,
      p<0.001). The %CI in the RR regions (10.4+/-10.4%) was significantly less than
      that in the normal regions (23.5+/-10.1%, p<0.001); however, no significant
      difference was found between the RR regions and those with a fixed defect (8.0+/
      7.2%). In patients with acute myocardial infarction, the regions showing the RR
      phenomenon on (99m)Tc-tetrofosmin SPECT have severely impaired LV wall
      contraction after exercise.

PMID- 14578615
TI  - Diabetes influences the cardiac symptoms related to atrial fibrillation.
AB  - It is well known that diabetes mellitus (DM) masks the cardiac symptoms during an
      ischemic heart attack, but there have not been reports of whether DM influences
      the subjective symptoms of atrial fibrillation (AF). The present study
      retrospectively assessed 65 patients who were revealed to be in sinus rhythm at
      their first visit to hospital and who had experienced episodes of AF (or
      paroxysmal AF) during the follow-up period. Compared with non-DM cases (n=50), DM
      patients (n=15) had a tendency to a more rapid heart rate in sinus rhythm (73+/-4
      vs 66+/-2, p=0.07) and higher averaged ventricular response at the first-recorded
      episode of AF (111+/-7 vs 99+/-3, p=0.10). However, the ratio of symptomatic
      cases at first-recorded AF tended to be lower in DM cases (33% vs 58%, p=0.08).
      When patients with beta-blockers or other antiarrhythmic agents were excluded,
      the ratio of symptomatic patients at first-recorded AF was significantly lower in
      the DM cases (25% vs 61%, p=0.04), although there was not a significant
      difference in averaged ventricular response at first-recorded AF (112+/-8 vs
      106+/-5). The prevalence of DM neuropathy was significantly higher in
      asymptomatic patients (70% vs 0%, p=0.01). DM may mask the cardiac symptoms of
      the first-recorded episode of AF, possibly because of DM neuropathy.

PMID- 14578616
TI  - Impact of diabetes mellitus on worsening of the left ventricular ejection
      fraction in exercise-gated 201Tl myocardial single photon emission computed
      tomography in patients with coronary artery disease.
AB  - It remains uncertain whether factors other than the severity of coronary artery
      disease (CAD) are associated with the worsening of the left ventricular ejection
      fraction (LVEF) by exercise. In the present study the impact of coronary risk
      factors on the worsening of LVEF by exercise was investigated in 391 patients
      with known or suspected CAD using exercise-gated (201)Tl scanning to calculate
      the LVEF. Significant worsening of the LVEF by exercise was defined as >4.7%
      (mean plus 1 SD of the value in 116 patients without CAD). Multivariate analysis
      revealed that diabetes mellitus (DM) was an independent risk factor for the
      worsening of LVEF by exercise in patients with multivessel (2- or 3-vessel) CAD
      with an odds ratio (95% confidence interval) of 2.2 (1.1-4.5, p=0.037). In 157
      patients with 2- or 3-vessel CAD, 20 (23.5%) of 85 nondiabetic patients and 31
      (43.1%, p=0.009 vs nondiabetic patients) of 72 diabetic patients showed
      significant worsening of LVEF by exercise. In patients with 2- or 3-vessel CAD,
      there was no significant difference in Gensini score or reversibility of
      perfusion defects between nondiabetic and diabetic patients. Thus, DM is a risk
      factor for worsening LVEF by exercise in addition to the severity of CAD.

PMID- 14578617
TI  - Patterns of coronary artery movement and the development of coronary
      atherosclerosis.
AB  - Mechanical stress in coronary arteries has been postulated to cause endothelial
      injury and atherosclerotic lesions, but the relationship between the pattern of
      coronary artery movement (CAM) and lesion severity is not known. In the present
      study CAM was classified into 10 patterns, which were grouped into 3 classes: (1)
      bend type = coronary artery flexes into a curve; (2) compression type = segmental
      length is shortened without vertical deviation of the artery; (3) displacement
      type = location of the coronary artery shifts without change of segmental length
      or shape. Assessment of CAM was made for 6 segments from the left anterior
      descending artery and 3-5 segments from the left circumflex artery, and in total
      673 segments were analyzed. Coronary arterial segments with the compression type
      had a significantly higher percent stenosis than those without it (Compression
      57.9+/-29.4 % vs Bend 7.9+/-19.0 %, Displacement 4.3+/-13.0 %; p<0.00001). The
      compression type was seen frequently in the proximal and mid left anterior
      descending artery, ostial diagonal branch, obtuse marginal branch and mid left
      circumflex artery. The critical CAM (eg, compression pattern) may be an important
      mechanical stress inducing coronary atherosclerosis.

PMID- 14578618
TI  - CXCR3 chemokine receptor-plasma IP10 interaction in patients with coronary artery
      disease.
AB  - In rat models of transplant vasculopathy, the strongest staining of CXCR3 is
      observed in the innermost layer of the neointima and because neointimal
      hyperplasia is seen after coronary angioplasty, the CXC chemokines may be targets
      for preventing stenosis. The expression of leukocyte surface chemokine receptors
      (CCR2/CCR5/CXCR2/CXCR3), as determined by flow cytometry, and plasma
      concentrations of monocyte chemoattractant protein (MCP)-1 and interferon
      inducible protein (IP)10, as determined by enzyme immunoassays, were investigated
      in 55 patients with coronary artery disease (CAD) who underwent percutaneous
      transluminal coronary angioplasty (PTCA) and 20 patients without significant
      coronary stenosis based on the results of coronary catheterization during the
      same period (C group). The patients with CAD were divided into 3 groups: 20 with
      de novo stenosis (D group), 15 with restenosis (R group) and 20 without
      restenosis (N group) after PTCA. CXCR3 expression on lymphocytes, but not
      monocytes, in the R group was significantly lower than that in the C group.
      Although the plasma concentrations of IP10 in the D and N groups did not differ
      from that in the C group, the concentration in the R group was significantly
      higher. Increased plasma concentrations of IP10 were accompanied by a
      compensatory decrease in the CXCR3 expression on lymphocytes, but not monocytes,
      suggesting that a high plasma concentration of IP10 strongly induces monocytes
      signaling. The CXCR3 - plasma IP10 chemokine receptor - chemokine interaction on
      monocytes may affect the development of coronary restenosis, but not de novo
      stenosis, in patients with CAD.

PMID- 14578619
TI  - Echocardiographic assessment of right ventricular obstruction in hypertrophic
      cardiomyopathy.
AB  - Echocardiography was used to evaluate the incidence, flow dynamics and
      morphological characteristics of right ventricular obstruction in 91 patients
      with hypertrophic cardiomyopathy. Color flow mapping was used to define the sites
      of obstruction in the left and right ventricles. Ventricular obstruction was
      considered to be present if the flow velocity was less than 2.0 m/s as measured
      by continuous wave Doppler. The thickness of both the right ventricular free wall
      and anterior ventricular septum was measured to assess the magnitude and extent
      of hypertrophy. Right ventricular obstruction was present in 14 patients of whom
      6 (43%) had left ventricular obstruction also. The right ventricular obstructions
      were found in the outflow tract (9 patients), mid-base septal bulge (2 patients)
      and apical trabecular region (3 patients). Doppler waveform was confined to
      systole in all patients with obstruction in the outflow tract and in one of the
      patients with mid-base septal bulge. Moreover, the flow wave persisted into early
      diastole in 4 patients, including 2 with apical trabecular obstruction. The
      thickness of both the right ventricular free wall and anterior ventricular septum
      suggested that these hypertrophied regions were the sites of right ventricular
      obstruction. Thus, echocardiography was useful in evaluating right ventricular
      obstruction in hypertrophic cardiomyopathy.

PMID- 14578620
TI  - Segmental pulmonary vein isolation for paroxysmal atrial fibrillation improves
      quality of life and clinical outcomes.
AB  - The purpose of this study was to clarify the change in the quality of life (QOL)
      and clinical outcomes following segmental pulmonary vein (PV) isolation for
      paroxysmal atrial fibrillation (AF) in 50 patients with drug-refractory,
      paroxysmal AF. The left superior, left inferior, and right superior PVs were
      targeted for isolation in all patients, and the right inferior PV was isolated in
      4 patients. AF recurred in 22 of 50 patients, and these patients were treated
      with class I or class III antiarrhythmic drugs that had been ineffective before
      the ablation procedure. The symptom severity and frequency was scored and the QOL
      was assessed using the Short-Form-36 questionnaire (SF-36) before the PV
      isolation and at the end of the follow-up period (6.0+/-3.0 months). PV isolation
      resulted in a reduction in the symptom severity (p<0.001) and symptom frequency
      (p<0.001) scores as compared with the pre-ablation values. Ninety percent of the
      patients had a >90% reduction in the frequency of symptomatic episodes of AF
      after the ablation procedure. The mean SF-36 physical and mental component
      summary scores also significantly improved after PV isolation as compared with
      the pre-ablation values (both for p<0.001). With a segmental isolation approach
      that targets at least 3 PVs, satisfactory improvement in the symptoms and QOL can
      be achieved in patients with drug-refractory, paroxysmal AF.

PMID- 14578621
TI  - Effects of atorvastatin therapy on the low-density lipoprotein subfraction,
      remnant-like particles cholesterol, and oxidized low-density lipoprotein within 2
      weeks in hypercholesterolemic patients.
AB  - The short- and intermediate-term pleiotropic effects of atorvastatin were
      investigated in 18 hypercholesterolemic patients, as well as the temporal
      differences in these pleiotropic effects. Atorvastatin was given for 3 months and
      fasting lipid concentrations, thiobarbituric acid reactive substances (TBARS),
      fibrinolytic parameters, and flow-mediated dilation of the brachial artery (FMD)
      were measured at baseline and after 2 weeks and 3 months of therapy. Atorvastatin
      reduced the total cholesterol (273+/-34 vs 188+/-31 mg/dl, p<0.0001), low-density
      lipoprotein-cholesterol (LDL-C: 174+/-28 vs 111+/-23 mg/dl, p<0.0001), small,
      dense LDL-C (34+/-22 vs 18+/-20%, p<0.01), remnant-like particles cholesterol
      (RLP-C: 8.8+/-6.0 vs 5.1+/-2.6 mg/ml, p<0.01), and TBARS (3.3+/-1.0 vs 3.1+/-0.9
      nmol/ml, p<0.05) after 2 weeks. Atorvastatin decreased the concentration of
      small, dense LDL-C again after 3 months (8+/-13%, p<0.0001). The plasma
      concentrations of the fibrinolytic parameters did not change significantly after
      3 months of atorvastatin therapy. FMD increased significantly after 2 weeks
      (5.6+/-2.1 vs 6.3+/-2.0%, p<0.01) and additionally increased after 3 months of
      therapy (8.3+/-1.9%, p<0.0001). There were no correlations between the
      pleiotropic effects and the improvement in the lipid profile. The results
      indicate some short-term pleiotropic effects of atorvastatin therapy within 2
      weeks, which may be important with respect to the early benefits of statin
      therapy.

PMID- 14578622
TI  - Does myocardial revascularization with multiple arterial grafts improve the
      prognosis of dialysis patients?
AB  - In the present study it was examined whether myocardial revascularization with
      multiple arterial grafts improves the prognosis of dialysis patients. The 20
      subjects underwent coronary artery bypass grafting over 2 vessels (extra
      corporeal circulation in 11 patients, off-pump bypass in 9 patients) and were
      divided into 2 groups according the number of arterial grafts. Group A consisted
      of 9 patients in whom more than 2 arterial grafts were used and Group B, 11
      patients requiring 1 internal thoracic artery and additional saphenous vein
      grafts. The surgical procedure was examined, as well as the short-term and long
      term results of both groups. There were no differences in the profiles of the 2
      groups. The mean arterial graft number in group A was 2.2+/-0.6 and 1.0+/-0.0 in
      group B. There was neither mediastinitis nor brain complication in either group.
      There were no operative deaths in group A and 1 in group B. The 55-month
      actuarial survival rate including all deaths, and estimated by cardiac deaths,
      was, respectively, 0.53+/-0.21 and 0.80+/-0.18 in group A and 0.42+/-0.21 and
      0.53+/-0.23 in group B. The survival rate estimated by cardiac death in group A
      was better, but there was not a significant difference. Myocardial
      revascularization with multiple arterial grafts for dialysis patients had good
      short-term results without increased operative risk and may improve the long-term
      results related to cardiac death. However, there was no significant difference in
      survival including all deaths because of the numerous non-cardiac deaths.

PMID- 14578623
TI  - Biphasic response of action potential duration to sudden sympathetic stimulation
      in anesthetized cats.
AB  - Although certain roles of the sympathetic nervous system have been suggested as
      possible mechanisms of life-threatening arrhythmias and sudden cardiac death, the
      dynamic electrophysiological response to sympathetic activation remains unclear.
      The aim of this study was to investigate the dynamic response of action potential
      duration (APD) to sudden sympathetic stimulation (SYM) using monophasic action
      potential (MAP) recording. In 10 anesthetized cats, MAPs were continuously
      recorded from the right ventricular endocardium under constant pacing. The
      dynamic response of the APD to SYM (3 Hz) were examined before and after the
      administration of propranolol (0.5 mg/kg i.v.) (n=5) or phentolamine (1.0 mg/kg
      i.v.) (n=5). In response to SYM, the APD was transiently prolonged by 5.5+/-3.2
      ms at 7.0+/-1.3 s, and monotonically shortened toward a steady-state level (
      14.5+/-6.9 ms). Propranolol almost abolished both the transient prolongation
      (6.6+/-4.5 to 0.2+/-0.4 ms, p<0.05) and the steady-state shortening (-13.7+/-3.6
      to -1.1+/-2.4 ms, p<0.005), whereas phentolamine did not have a significant
      effect on the response of APD to SYM. These findings might partly account for the
      propensity of ventricular arrhythmias to occur immediately after sudden
      sympathetic activation.

PMID- 14578624
TI  - Gene expression of cardiac mast cell chymase and tryptase in a murine model of
      heart failure caused by viral myocarditis.
AB  - This study examined the gene expression of mouse mast cell proteases to clarify
      their role in the pathophysiology of viral myocarditis. Male DBA/2 mice were
      inoculated intraperitoneally with the encephalomyocarditis virus and the gene
      expression of mast cell chymase, mouse mast cell protease (mMCP)-4 and -5, and
      tryptase, mMCP-6, matrix metalloproteinase (MMP)-9 and type-I procollagen was
      measured by real-time quantitative RT-PCR analysis. The gene expression of mMCP
      4, -5 and -6 mRNA was increased at 5 days, and continued to increase to day 14,
      coinciding with a prominent inflammatory reaction and extensive myocardial
      necrosis and fibrosis. The gene expression of MMP-9 was also increased, and there
      was a significant correlation between upregulation of mast cell proteases and MMP
      9. The gene expression of type-I procollagen was increased at 5 days and
      continued to increase to day 14, suggesting that a fibrotic process had already
      begun during the acute stage of viral myocarditis. These findings suggest that
      mast cell chymase and tryptase participate in the acute inflammation and
      remodeling process of viral myocarditis.

PMID- 14578625
TI  - Ischemia in the territory of the first major septal perforator branch anomalously
      originating from the first diagonal branch leads to a transient leftward shift of
      the QRS axis in the frontal plane: a case report.
AB  - A patient with non-Q wave myocardial infarction had severe luminal narrowing in
      the first major septal perforator branch, which arose anomalously from the first
      diagonal branch. In this case, an exercise ECG showed a transient leftward QRS
      axis shift.

PMID- 14578626
TI  - Vascular surgery using argatroban in a patient with a history of heparin-induced
      thrombocytopenia.
AB  - For patients with a history of heparin-induced thrombocytopenia (HIT) who undergo
      cardiac or vascular surgery, the optimal anticoagulation substitute for heparin
      has yet to be established. Recombinant hirudin has been recommended; however,
      this agent is unsuitable for patients with renal dysfunction. Argatroban was used
      in the present patient who had a history of HIT and renal dysfunction and
      required peripheral vascular surgery. Argatroban was easy to monitor and control,
      regardless of renal function, and has advantages over other anticoagulants for
      such patients.

PMID- 14578627
TI  - Myocardial infarction in a patient with severe aortic stenosis and normal
      coronary arteriograms: involvement of the circumferential subendocardial wall of
      the left ventricle.
AB  - A case of severe aortic stenosis with normal coronary arteriograms was associated
      with myocardial infarction involving the circumferential subendocardial wall of
      the left ventricle. The infarct was caused solely by the severe aortic stenosis
      and resulted from the extreme disparity between myocardial oxygen supply and
      demand.

PMID- 14578628
TI  - Novel application of the hemostatic device TOMETA KUN.
AB  - A 79-year-old woman was admitted with worsening chest discomfort and diagnosed as
      having an acute myocardial infarction. She underwent emergency coronary
      angioplasty via the transradial artery, but during surgery the proximal portion
      of the radial artery was perforated by a wire injury. The TOMETA KUN compression
      system (Zeon Medical, Tokyo, Japan) was used for hemostasis at the perforation
      site and enabled an anterograde flow to be maintained in the radial and ulnar
      arteries without extravascular leakage. In addition to stabilizing the arterial
      perforation, the device allowed the successful completion of the percutaneous
      coronary intervention procedure without the need to cease anticoagulant therapy.

PMID- 14578629
TI  - Intravenous administration of nifekalant hydrochloride for the prevention of
      ischemia-induced ventricular tachyarrhythmia in patients with renal failure
      undergoing hemodialysis.
AB  - Excretion in the urine is an important pathway for the elimination of nifekalant
      hydrochloride (NIF), a novel class III antiarrhythmic agent. Three patients with
      renal failure were undergoing hemodialysis and receiving NIF for the prevention
      of ischemia-induced ventricular tachyarrhythmia. Because NIF is not dialyzed,
      dose adjustment at relatively low concentrations was required, with monitoring of
      the QT interval.

PMID- 14578630
TI  - [The Department of Histology and Embryology of Kaunas University of Medicine
      celebrates its 80th anniversary].
AB  - The Department of Histology and Embryology at Kaunas University was established
      in 1923. Professor E. Landau was the very first to head the Department. He
      arrived in Kaunas from the University of Bern (Switzerland) and worked here from
      1923 till 1932. At that time the staff of the Department had only four people:
      professor E. Landau, head of the Department, J. Bubenaite, senior assistant, D.
      Kesiunaite, assistant, and J. Masevicius, laboratory assistant. From 1934 till
      1937 the Department was headed by professor V. Danchakova, who came from
      Columbian University in New York. From 1939 till 1971 the Department was headed
      by professor B. Abraitis, and from 1971 till 1994 by professor A. Vitkus. In 1994
      associate professor K. Baltrusaitis was elected head of the Department. At
      present time the staff has five lecturers and four laboratory assistants. Various
      preparations for histology classes are being produced by the laboratory and
      teaching personnel. According to the curriculum requirements, lectures courses of
      histology, cytology and embryology are delivered to the first and second year
      students of the Faculties of Medicine, Odontology, Nursing and Public Health,
      taking into account specific aspects of each speciality. An optional course is
      also provided to senior students wishing to study the problems of histogenesis
      and changes associated with aging of body tissues. In 2003 professor A.
      Valanciute was elected head of the Department. The main research problem deals
      with experimental ischemic heart disease and the solution of problems of
      experimental myocardial infarction. The results of all thesis research works can
      be summed pointing out 12 presented inventions and more than 20 rationalizations.
      Staff of the Department also takes part in the realization of an international
      project called "Biotechnet".

PMID- 14578631
TI  - Prof. Eber Landau, the very first chief of Histology and Embryology Department at
      the University of Lithuania.
AB  - The article deals with the scientific activities of professor Eber Landau carried
      out in Estonia, Lithuania and Switzerland. Professor E. Landau was born November
      8, 1878, in a merchant's family in Rezekne, Latvia. On leaving a classical high
      school in Riga, E. Landau studied at the Medical Faculty of Tartu University,
      graduating it in 1902. Later he improved his qualification in histology and
      anatomy at Villafrenk Zoology station, at the Histology Laboratory in Munich, and
      in St. Petersburg under the guidance of professor P. Leshaft. In 1906-1912 Landau
      worked as a prosector assistant at the Anatomy Institute, headed by professor A.
      Rauber, Tartu University. In 1912 he was elected a director of the Anthropology
      Institute, Tartu. On the outbreak of the First World War, E. Landau, as a Russian
      citizen, was called to the army and served as a neurologist and psychiatrist in
      Paris military hospitals. In 1918, E. Landau returned to Bern and for 5 years
      worked at the Anatomy Institute headed by prof. H. Strasner. In December 1, 1923,
      E. Landau moved to Kaunas University. Here he established the Department of
      Histology and Embryology and headed the Department till 1932. From 1932 till 1950
      Eber Landau worked as a professor at the University of Lausanne. Professor E.
      Landau retired in 1950, but he still continued his research work in the field of
      neurohistology. Professor E. Landau died October 30, 1959. He left behind him an
      ample scientific heritage: 175 scientific publications and 12 doctoral theses
      done under his guidance.

PMID- 14578632
TI  - [Peculiarities of myocardial remodelling in rabbits' experimental
      hypercholesterolemia].
AB  - The aim of the investigation was to estimate the peculiarities of myocardial
      remodelling on the conditions of experimental hypercholesterolemia. Experiments
      were carried out on chinchilla breed male rabbits weighing from 2.3 to 3.0 kilos
      and being of three-four months of age (15 rabbits). Rabbits were fed daily with
      0.2 g/kilo of cholesterol during twelve months. We defined the percentage volume,
      perimeter and the number of separate fibers per field of collagenous matrix and
      the volume of cardiomyocytes by computerized image analysis system connected with
      the microscope by CCD camera. We defined that various degree of stenosis of
      epicardial coronary arteries and their intramural branches leading to absolute
      lumen narrowing due to long duration of hypercholesterolemia (12 months) is the
      cause of chronic ischemia and remodelling of the myocardial structures of left
      and right ventricles. In case of chronic ischemia, cardiomyocytes in the left
      ventricle are replaced by multifocal reparative fibrosis, in the right ventricle
      such changes were not observed. Percentage volume of interstitial collagenous
      fibres increases about 1.2 (p<0.05) in the left ventricle and 1.26 times (p<0.05)
      in the right ventricle, i. e. interstitial fibrosis is being formed.

PMID- 14578633
TI  - Changes of activated macrophages and apoptotic cell count in the organs of rats
      during experimental sepsis.
AB  - OBJECTIVE: Leukocyte migration plays an important role in inflammation. The aim
      of our study was to detect the activated macrophage count and to define the
      apoptotic cell count in the rat's liver and lungs during different stages of
      sepsis and to clarify whether the activity of macrophages is associated with the
      apoptotic cell count in the course of the septic process. MATERIAL AND METHODS:
      Experimental sepsis was induced by inoculating Wistar rats intraperitoneally with
      E. coli cells. The liver and lung tissue was obtained 2, 6, 24, 48 and 120 hours
      after inoculation, and blood smears to detect the leukocyte volume were prepared
      at the same time. Macrophage activity was studied by immunohistochemical
      staining, using the ABC method. Apoptotic cell count was detected with the "In
      Situ Cell Death Detection Kit". RESULTS: Decrease in the total count of leukocyte
      and lymphocyte percentage and a rise in the percentage of neutrophils in the
      blood were evidences of a strong inflammation process in an organism. The count
      of activated macrophages in the liver was high, showing the maximum level at the
      end of the 2(nd) h after inoculation, after which it began to fall. Apoptotic
      cell count rose after a decrease in macrophage activity. In the lungs both
      changes - a decrease in activated macrophage level and a rise in the apoptotic
      cell count took place later on. CONCLUSION: Our investigations indicate that a
      decrease in the activated macrophage level is connected with an increased rise in
      the apoptotic cell count in both organs depending on the stage of the disease and
      occurs in the liver earlier than in the lungs but the process of cell apoptosis
      was more intensive in the lungs.

PMID- 14578634
TI  - Callus area and glycosaminoglycans content of the traumatized tibia in rats.
AB  - The aim of the present work is the quantification of the post-traumatic bone
      healing histology (total callus morphometry) and histochemistry of the
      glycosaminoglycans (GAG) content (microspectrometry) in rats tibia after segment
      osteotomy and bicortical perforation of trained and immobilized animals. MATERIAL
      AND METHODS: A quantified investigation of post-traumatic bone repair histology
      and GAG content after osteotomy and perforation of tibia in 105 young adult male
      Wistar rats has been performed. The repair was studied in normal and affected
      (training and immobilization) animals at 1-42 days after operation. RESULTS: The
      posttraumatic bone repair is an ordinary process of osteohisto- and
      organogenesis, and dependent on the environment factors (mode and degree of
      trauma, training of animals, etc.). The repair is trauma-dependent; after
      osteotomy the total callus area is significantly larger respectively to
      perforation. Otherwise, the training did not significantly influence the repair
      callus area and GAG content and therefore did not accelerate the bone repair,
      whereas the immobilization of animals depressed these processes and the bone
      repair was inhibited. CONCLUSIONS: Quantified study of histology and
      histochemistry of bone repair after perforation gave important new, more detailed
      results on the reparative histogenesis of the bone tissues: repair dynamics of
      callus areas, dynamics of GAG concentration, effects of mode and degree of
      trauma, training and immobilization on the repair process.

PMID- 14578635
TI  - Features of elastic tissue staining and its arrangement in the wall of human
      basilar artery.
AB  - OBJECTIVES: 1. To evaluate the effectiveness of the main elastic tissue staining
      methods in a. basilaris. 2. To study the arrangement of elastic fibers in human
      a. basilaris wall. MATERIALS AND METHODS: For anatomical material we used a.
      basilaris removed from cadavers of ten people who died from violent death, their
      age ranging from 21 to 30 years. We studied histological structure staining by
      Hematoxylin-Eosin, Orcein, Gomori and Van Gieson methods. The samples were
      examined under the microscope "Zeiss-Standart 25" and photographed with a MC80DX
      photocamera. RESULTS: The internal elastic lamina was distinctly seen while
      staining by Hematoxylin-Eosin, Orcein, Gomori and Van Gieson methods. The elastic
      fibers and muscle cells of the middle layer were hardly distinguished. We found
      collagen fibers and several elastic fibers in the external layer of the vascular
      wall. We studied the arrangement of elastic fibers in medial and cranial segments
      of human a. basilaris wall. CONCLUSIONS: Several staining methods have to be
      provided to differentiate the elastic fibers from collagen fibers and muscle
      cells in the best way, because only complex staining enables to differentiate one
      from another. Human a. basilaris has a mixed elastic-muscular structure. The
      elastic tissue distributes gradually in medial and cranial segments of a.
      basilaris medial layer. There is thin, sharp, solid and undulate internal elastic
      lamina in the internal layer. There are elastic fibers, smooth muscle cells and
      several collagen fibers in the middle layer of the vessel. The external layer of
      a. basilaris consists of several elastic fibers and the main part is occupied by
      collagen fibers.

PMID- 14578636
TI  - The morphological and functional basis of the new conception about the suprarenal
      cortex regeneration.
AB  - The exhaustion of main intracellular and cellular reserves of the regeneration in
      suprarenal cortex under the influence of exogenous hyperthermia activates the
      supplementary sources of cellular regeneration. First type of low differentiated
      cortical cells appears under the outer connective tissue capsule on approximately
      the 7(th) day of hyperthermia. These cells proliferate and some of them migrate
      along the cortical blood capillaries towards the deep portion of zona
      fasciculate. They differentiate into the typical cortical cells (spongiocytes) of
      zona glomerulosa and zona fasciculate according to their location. Second type of
      low differentiated cortical cells appears through one circadian-septal period
      (during 7 days) near the inner connective tissue capsule that separate cortex
      from the medulla. This cell type gradually differentiates into the typical
      cortical cells of zona reticularis. Stem cortical cells were found in suprarenal
      cortex. They did not have specific morphological signs and could synthesize
      nucleus DNA.

PMID- 14578637
TI  - Evaluation of peculiarities of the acetylcholinesterase-positive nerve plexus and
      its length in the cornea.
AB  - The objective of this study was to evaluate age-related peculiarities of
      acetylcholinesterase-positive nerve plexus and its length in the dog cornea.
      MATERIAL AND METHODS: Nine mixed breed dogs (male and female) of 1.8-20 kg weight
      were used. They were divided into three age groups: young (until 1 year), adult
      (1-7 years) and old (8 and more years). Acetylcholinesterase-positive nerve
      plexus was identified using acetylcholinesterase method of M. J. Karnowsky and L.
      A. Roots (1964) modified by D. H. Pauza et al. (1996). The length of nerve
      bundles was measured by mm in 1 mm(2) of cornea. RESULTS AND CONCLUSIONS:
      Branching thick, medium and thin nerve bundles form acetylcholinesterase-positive
      nerve plexus in dog cornea. The average of the length of nerve bundles between
      the left and the right corneas was similar in different age groups (p>0.05). The
      length of acetylcholinesterase-positive nerve bundles in 1 mm(2) of the cornea in
      the group of adult dogs (10.32+/-0.11 mm) was higher than in the groups of young
      (9.42+/-0.02 mm) and old dogs (7.75+/-0.14 mm) (p<0.001).

PMID- 14578638
TI  - [Microstructure of dental cementum and individual biological age estimation].
AB  - Evaluation of annual incremental lines of dental cementum is one of potentially
      valuable methods for biological age estimation in forensic anthropology. The
      objective of this work was to elucidate the relation between the number of those
      lines and the chronological age of an individual. Material of the study consisted
      of undecalcified sections of 227 permanent teeth of 178 individuals (89 males, 89
      females, average age 47.5 years) (3-4 of each tooth, thickness 33-35 mum).
      Sections were analyzed under magnification of 20-40 times, photographed and
      evaluated using digitalized visual analysis system. Biological age was estimated
      by pooling the number of lines counted and the average age of tooth eruption. It
      was found that the number of lines strongly correlates with the chronological age
      (r>0.95, p<0.001). Factor of sex has no significant influence on the number of
      lines. Absolute average error was 5.58 years (11.75%), but the preciseness of the
      method decreases with age: among younger individuals it is lower - 3.71 years
      (10.09%), and higher among older - 7.86 years (13.1%). Regression power equation
      produces higher error than the traditional method: the best results are obtained
      by pooling the number of lines and average age of tooth eruption. Conclusion is
      made that the method is suitable for forensic anthropology, and digitalized
      system enhances the count and provides better results.

PMID- 14578639
TI  - Alpha B-crystallin in corpora lutea of pseudopregnant rat.
AB  - Localization sites and labeling intensity of alphaB-crystallin in corpus luteum
      (CL) of pseudopregnant rats has been studied using postembedding light and
      electron microscopical immunohistochemistry. At days 2 and 18 alphaB-crystallin
      labeling was found to be significantly higher compared with the luteal
      maintenance period (days 6 and 10). alphaB-crystallin localized both to luteal
      and interstitial cells of CL. At light microscopical level alphaB-crystallin
      labeling decreased during CL life span in the central area of luteal cells
      cytoplasm and increased in the peri-plasmalemmal area. Interstitial cells
      labeling was found to increase at day 6, followed by almost complete
      disappearance during functional luteolysis (days 15 and 18). Our results at
      electron microscopical level showed alphaB-crystallin to localize in cytoplasm
      with close relationship with endoplasmic reticulum, Golgi apparatus, mitochondria
      and also in nuclei of luteal and interstitial cells. At day 2 labeling of luteal
      cells was abundant in cytoplasm but weak in nuclei. During the luteal maintenance
      period and functional luteolysis labeling in luteal cells was relocalized to the
      peri-plasmalemmal and perinuclear areas. Labeling in nuclei of luteal cells was
      weak. At the same time (day 6) interstitial cells including nuclei showed strong
      labeling, which was significantly decreased during luteolysis.
      Immunohistochemically detectable tubulin decreased in CL tissue during CL life
      span allowing to suggest that alphaB-crystallin acts as chaperone, one possible
      role of which is to stabilize the cytoskeleton in different CL cell types during
      CL formation and active functioning.

PMID- 14578640
TI  - Ultrastructural changes in the remnant kidney (after 5/6 nephrectomy) glomerulus
      after losartan and atenolol treatment.
AB  - The aim of our study was to investigate the effect of losartan on the changes in
      the early stages (at week 4) of experimental chronic renal failure after 5/6
      nephrectomy compared with the impact of atenolol. Attention was focused on the
      ultrastructural changes in the renal corpuscles. Twenty-seven male Wistar rats
      were divided into three groups: nephrectomized group, nephrectomized losartan
      treated group and nephrectomized atenolol-treated group. Rats were kept in a
      climate-controlled facility, where animals were housed under standard conditions
      on a 12-hour light/dark cycle and fed with standard rodent chow. Angiotensin
      receptor antagonist losartan (180 mg/L) or beta-blocking agent atenolol (750
      mg/L) was added to the drinking water and treatment was started on the first day
      after the operation. Systolic blood pressure and 24 hour protein excretion was
      measured every week. Nephrectomized rats had higher proteinuria and systolic
      blood pressure than the treated rats. Rats were killed 4 weeks after surgery.
      Early stage renal disease was characterized by glomerular hypertrophy and focal
      segmental glomerulosclerosis. The morphological study revealed that
      ultrastructural changes in the atenolol-treated group were smaller than those in
      the nephrectomized and losartan-treated groups. Glomerular basement membrane
      (GBM) thickness was significantly increased in losartan-treated (206.8 nm) and
      atenolol-treated (198.8 nm) rats compared to nephrectomized (169.2 nm) rats. The
      podocytes demonstrated hypertrophy and foot process effacement, especially in
      nephrectomized group. In conclusion, our results show that firstly, treatment
      with losartan and atenolol significantly increased GBM thickening and secondly,
      treatment with atenolol reduced ultrastructural changes in the podocytes.

PMID- 14578641
TI  - [Elbow joint formation in grafts of the limbs lacking the anterior or posterior
      necrotic zones].
AB  - The purpose of this experimental work is to examine the joint formation in limb
      bud grafts lacking the anterior or posterior necrotic zones where programmed cell
      death (apoptosis) occurs. METHODS: The embyonic chick limbs were transplanted
      onto the chorioallantoic membrane. The limbs of experimental group were
      transplanted without the prospective anterior or posterior necrotic zones.
      Transplants containing all limb bud material served as the control group.
      RESULTS: Most experimental grafts showed wide or complete fussions of the bones
      forming the elbow joint in the early developmental stages. The regression of the
      elbow joint in the control grafts was gradually progressive: from the narrow
      cartilaginous bridges between articular surfaces in early stages to extensive
      fusion of bone primodia in late developmental stages. CONCLUSIONS: The
      elimination of the anterior or posterior necrotic zones suppressed apoptosis in
      the "opaque patch" and caused the fussion of the bones in elbow joint.

PMID- 14578642
TI  - [The defect of the breast managed by subaxillary flap after breast cancer
      removal].
AB  - The treatment of early breast cancer by breast conserving therapy should ensure
      the local control and accebtable cosmetic result. To repair the defect caused by
      the partial mastectomy in upper inner quadrant various methods of plastic
      reconstruction should be used. Eight patients underwent breast conserving therapy
      due to cancer in upper inner quadrant. The subaxillary flap was used for the
      reconstruction of the defect with good cosmetic effect. The best oncological and
      cosmetic result is achieved by breast surgeon, competent in oncology and plastic
      surgery, or by multidisciplinary approach.

PMID- 14578643
TI  - [Indications for surgical treatment of Parkinson's disease and outcome].
AB  - There is no single opinion about the indications and best method of surgical
      treatment of Parkinson's disease. We presented the most common indications for
      surgery and evaluated the results of stereothalamotomies and stereopallidotomies,
      performed in our clinic, analyzed their effectiveness on the main motor symptoms
      of parkinsonism. During the last 29 years we performed 219 thalamotomies (45
      bilateral) and 131 pallidotomies (23 bilateral) on 279 patients. Pallidotomy of
      the same side was repeated for 3 patients to correct the size of too small
      destruction and shortlasting effect. Good effect for parkinsonian tremor was
      achieved in 89.54% of patients after thalamotomies and in 77.42% after
      pallidotomies; for rigidity in 84.4% after thalamotomies and 83.15% after
      pallidotomies; for hypokinesia in 55% after pallidotomies and 6.5% after
      thalamotomies. In both types of operations the best effect was observed on the
      controlateral side. Bilateral effect (less on the ipsilateral side) was present
      in 5.17% of unilateral thalamotomies and in 14.28% of pallidotomies.

PMID- 14578644
TI  - Radiofrequency fistulotomy in anal fistula. An alternative to conventional
      surgical fistulotomy.
AB  - Most of surgeons prefer fistulotomy by laying open technique in treating
      different types of anal fistula. We used the radiofrequency fistulotomy procedure
      in 136 cases of various types of low anal fistulae in a one-year period. The
      patients were followed for 18 months. The average time for complete wound healing
      was 37 days and additional follow-up was continued for 7 days. Delayed wound
      healing occurred in 7 patients. It failed completely in 2 patients and 3 were
      lost to follow up. No patient had interference with continence. Radiofrequency
      fistulotomy method was effective with easy tissue excision and minimum bleeding.
      It permitted use in deep and difficult areas like the adjoining tracts. The
      failure rate was 3.7%.

PMID- 14578645
TI  - [The prevalence and trends of the smoking habits among middle-aged Kaunas
      population during 20 years and their relation with sociodemographic status].
AB  - THE AIM: To evaluate the prevalence and time trends of smoking habits among
      middle-aged Kaunas population during 20 years and its relation with
      sociodemographic status. MATERIAL AND METHODS: Four cross-sectional surveys were
      carried out according to the WHO MONICA protocol in 1983-1985, 1986-1987, 1992
      1993, and 2001-2002. During these surveys, 2,450, 1,762, 1,238, and 1,404 persons
      aged 35-64 years, respectively, were screened. Data of the last survey were used
      to evaluate the relationship between smoking habits and sociodemografic status
      (educational level, occupation). Data of all four surveys were used to assess the
      prevalence of smoking habits among the Kaunas population aged 35-64 years and its
      trends during 20 years. Regular smoker was subject who smoked at least one
      cigarette per day. Prevalence rates for age group of 35-64 years were age
      standardized using the European population as the standard. RESULTS: According to
      the results of the last survey, 41.4% of men and 11.3% of women were regular
      smokers. During the last twenty years the prevalence of regular smokers increased
      by 2.7-fold among women and didn't change among men. Age, educational level,
      occupation and age when starting smoking showed a strong relationship with the
      smoking habits among men. Education level didn't show any association with
      smoking habits among women. The lowest prevalence of the regular smoking was
      among men with a higher education (24.9%) and among professional workers (27.1%)
      as compared to those with a lowest education (44.6%, p<0.01) and workers (47.3%,
      p<0.001), respectively. Among all regular smokers, 65.2% of men started to smoke
      at age 16-21 years, and 52.3% of women - at age 22 years or more. During 20-year
      period the prevalence of never smokers decreased (beta=-0.95, p<0.05) and that of
      ex-smokers increased (beta=0.96, p<0.05) among women. No statistically
      significant trends in smoking habits were detected among men during the study
      period. CONCLUSION: The prevalence of never smokers decreased and that of ex
      smokers increased among women 2.7-fold while no significant changes in smoking
      habits were found among men during 20-year study period. The lowest prevalence of
      regular smokers was among men with higher education and among professional
      workers.

PMID- 14578646
TI  - [Motivation to participate in mammography screening program for breast cancer].
AB  - The rates of incidence and mortality of breast cancer in Lithuania are
      increasing. The causal prophylaxis is unknown. The early mammography diagnosis
      improves results of treatment. The aim of the study is to investigate the
      motivation to participate in mammography screening program for breast cancer and
      to evaluate the relationship between these motives and women age, education,
      family history, personal income. Two hundred three women were interviewed about
      the motivation to participate in mammography screening program for breast cancer.
      The strength of motivation was estimated in parametric variable. It was attempted
      at evaluating the influence of age, education, family history and personal income
      on the level of motivation. Logistic analysis was used. Asymptotic women
      participated in mammography screening program for breast cancer. Complaints about
      their breasts as a motive to participate indicated only 31.8% of all women. After
      the survey it was observed that women understand the danger of breast cancer
      (86.1%) and believe that early diagnosis can protect from the poor outcome of the
      disease. Out of interviewed women, 85.3% (independently from their income, age,
      education and family history) think that it is essential for every woman to
      participate in mammography screening program for breast cancer. The majority of
      all surveyed women were informed about the program by their doctors. This motive
      became the main one to consult about breast cancer for 63% of women. The mass
      media made no significant impact to participate in mammography screening program
      for breast cancer.

PMID- 14578648
TI  - [Cementless total hip replacement in patients with high total dislocation: the
      results of femoral shortening by subtrochanteric segmental resection].
AB  - OBJECTIVES: We evaluated the results of femoral shortening by subtrochanteric
      segmental resection in patients who underwent total hip replacement (THR) for
      high total dislocation of the hip. METHODS: We performed THR in 19 hips of 16
      patients (15 females, 1 male; mean age 41 years; range 22 to 55 years) with high
      total dislocation of the hip. All the patients had severe hip pain. In all cases,
      femoral shortening by subtrochanteric segmental resection and an anatomical
      reconstruction of the acetabulum were performed with the use of cementless
      femoral components and cementless acetabular components with screws,
      respectively. The Harris hip scoring system was used for functional assessments.
      Radiologic assessments were based on the DeLee and Charnley criteria for the
      acetabular component, and on the Gruen zones and the Engh criteria for the
      femoral component. The mean follow-up period was 44 months (range 22 to 79
      months). RESULTS: Union was achieved in all cases in a mean of 14 weeks (range 11
      to 15 weeks). The mean leg length discrepancy decreased from 4 cm to 1.5 cm
      postoperatively. A positive Trendelenburg sign was found in 13 patients and four
      patients before and after surgery, respectively. The mean Harris hip score
      improved from 37 to 83 postoperatively. None of the patients developed deep
      infection, dislocation, sciatic nerve palsy, or nonunion at the osteotomy site.
      No clinical and radiologic signs of loosening were observed and no revisions were
      required. CONCLUSION: Femoral shortening with subtrochanteric segmental resection
      in THR is a safe technique in patients with high total dislocation of the hip,
      leading to satisfactory functional results.

PMID- 14578647
TI  - [The update on pancreatic cancer chemotherapy].
AB  - In the world five-year overall survival of patients with pancreatic cancer is
      low, i.e. about 5-6%. Patients without treatment live few months. Patients with
      pancreatic cancer are treated with combined treatment modalities. Chemotherapy is
      one of the three treatment methods. In the article we review chemotherapeutic
      agents that are used in everyday practice like fluorouracil and it's use in
      combination with other chemotherapeutic agents, and also, new drugs like
      gemcitabine, taxanes, capecitabine and other. Effectivity of the treatment with
      these agents, results of survival, toxicity and particularities of intraarterial
      chemotherapy are discussed. New perspectives in the treatment of patients with
      pancreatic cancer and methods of new chemotherapeutic strategies are analyzed.

PMID- 14578649
TI  - [An evaluation of the types and the results of surgical treatment for congenital
      scoliosis].
AB  - OBJECTIVES: We evaluated the types and the results of surgical treatment
      performed for congenital scoliosis. METHODS: Forty-one patients (26 females, 15
      males; mean age 12.8 years) with congenital scoliosis were included. The patients
      were classified according to the Winter's system. Transpedicular
      hemiepiphysiodesis, "egg shell" procedure, and anterior hemiarthrodesis and
      posterior convex fusion were performed in infantile (n=1) and juvenile (n=8)
      patients. In the adolescent (n=32) group, posterior in situ fusion was performed
      for rigid curves (n=15), posterior fusion after correction with posterior
      instrumentation for moderate curves (n=8), and posterior fusion and correction
      with posterior instrumentation after an anterior osteotomy for segmentation
      failures (n=6). Five patients with unincarcerated fully segmented hemivertebrae
      had anterior or posterior instrumentation following anterior-posterior
      hemivertebrectomy. The mean follow-up was 51.8 months (range 26 to 132 months).
      RESULTS: Fourteen patients (34.2%) had formation failures, 19 patients (46.2%)
      had segmentation failures, and eight patients (19.6%) had mixed types of
      deformities. Klippel-Feil syndrome was detected in two patients, and heart valve
      abnormality was found in two patients. Although the infantile patient who
      underwent transpedicular hemiepiphysiodesis showed no improvement after surgery,
      a spontaneous correction rate of 60% was found during her final controls.
      Patients who underwent anterior hemiarthrodesis obtained a final correction rate
      of 54.3% following a 42% of correction at surgery. The correction rates for
      posterior instrumentation were 26.2% with translation and 49.3% after an anterior
      osteotomy. Patients who had anterior or posterior instrumentation after anterior
      posterior hemivertebrectomy had final correction rates of 73.3% and 59.2%,
      respectively. Final evaluations showed that nine patients (21.9%) had no change
      in their curves, while 10 patients (24.4%) had spontaneous correction. Four
      patients developed superficial (n=2) and deep (n=2) infections following
      posterior instrumentation. Of these, three patients were successfully treated
      with debridement and antibiotic therapy, whereas one patient required implant
      removal in the eighth month. No neurologic deficits or systemic complications
      occurred during or after surgery. CONCLUSION: Surgical treatment may yield
      successful results in progressive congenital scoliosis when an appropriate
      surgical technique is selected based on the patient's age and the type of
      deformity.

PMID- 14578650
TI  - [Treatment of trimalleolar fractures. Is osteosynthesis needed in posterior
      malleolar fractures measuring less than 25% of the joint surface?].
AB  - OBJECTIVES: We evaluated the effect of posterior malleolar fractures, which
      measured less than 25% of the joint surface, on the results of ankle fractures.
      METHODS: The study included 44 patients (21 females, 23 males; mean age 44 years;
      range 17 to 76 years) who underwent surgical treatment for Weber types B or C
      ankle fractures. Fibula fractures were associated with deltoid ligament ruptures
      in 12 patients, and with medial malleolar fractures in 32 patients. Sixteen
      patients and 28 patients with and without posterior malleolar fractures,
      respectively, were evaluated as separate groups according to the Phillips'
      criteria for comparison of clinical, anatomical, and arthritic scores. The mean
      follow-up was 29.5 months (range 18 to 64 months). RESULTS: There were no
      significant differences between the two groups with regard to clinical and
      anatomical scores. Although the mean arthritic score was higher in patients with
      a posterior malleolar fracture, it did not reach significance (p>0.05).
      CONCLUSION: Our data show that satisfactory results can be achieved in posterior
      malleolar fractures measuring less than 25% of the joint surface when an
      acceptable reduction is performed even without osteosynthesis.

PMID- 14578652
TI  - [Surgical treatment of volar wrist ganglia].
AB  - OBJECTIVES: We evaluated surgery-related issues concerning the excision of volar
      wrist ganglia in the light of data obtained from our patients. METHODS: The study
      included 40 patients (10 males, 30 females; mean age 32.5 years; range 18 to 65
      years) who underwent surgery for volar ganglia. All the patients had unilateral
      involvement. All operations were performed under axillary brachial plexus
      regional anesthesia in the microsurgery operating room. The mean follow-up period
      was 2.5 years (range 1 to 5 years). RESULTS: The ganglia originated from the
      radioscaphoid joint capsule in 18 patients (45%), scaphotrapezial joint capsule
      in 16 patients (40%), and from the flexor carpi radialis tendon in two patients
      (5%). The ganglia were attached to the radial artery in 26 patients (65%), in two
      patients (5%) the radial artery completely merged into the lesion. The pedicles
      could not be dissected in four patients (10%), all of whom developed recurrences.
      Complications included recurrences in nine patients (22%), injury to the median
      palmar cutaneous nerve in four patients (10%), injury to the radial artery in two
      patients (5%) and wrist stiffness in five patients (12.5%). No significant
      correlation was found between complications and experience of the operating
      surgeons. CONCLUSION: Considering possible dissections and interventions for
      complication-associated repairs, and potential recurrences, surgical removal of
      volar ganglia should be performed under appropriate circumstances, especially in
      a formal operating room.

PMID- 14578651
TI  - [Surgical treatment of elbow fracture-dislocations seen in children and
      adolescents].
AB  - OBJECTIVES: We evaluated surgical indications and radiologic features of elbow
      fracture-dislocations in children and adolescents. METHODS: Thirteen patients (12
      boys, 1 girl; mean age 13 years; range 6 to 17 years) with elbow fracture
      dislocations were treated surgically. Coexisting fractures included medial
      epicondyle fractures (n=5), medial and lateral epicondyle fractures (n=3), radial
      head and olecranon fractures (n=2), radial head and medial epicondyle fractures
      (n=1), lateral condyle fracture (n=1), and fracture of the coronoid process
      (n=1). Eleven dislocations were closed, two were open. Open reduction and
      Kirschner wire fixation were performed in all the patients. Posterior (n=6),
      medial (n=5), anteromedial, and lateral incisions were used. Active range of
      motion exercises were initiated following the removal of sutures. Above-elbow
      cast was applied for three weeks. The mean follow-up period was 38 months (range
      7 to 58 months). The results were evaluated with the use of the Mayo elbow
      performance score. RESULTS: Ten patients had satisfactory (very good or good)
      results, while two patients with open dislocations and ipsilateral major
      injuries, and one patient who developed myositis ossificans postoperatively had
      unsatisfactory (moderate or bad) results. No postoperative nerve injuries were
      detected. CONCLUSION: The surgical indications for fracture-dislocations of the
      elbow in children and adolescents are the presence of intraarticular loose bodies
      or instability after reduction. The presence of open dislocation or ipsilateral
      major injuries are associated with unsatisfactory results.

PMID- 14578653
TI  - [Allogeneic blood transfusion policy in orthopedic surgery].
AB  - OBJECTIVES: This retrospective study was performed to evaluate transfusions in
      orthopedic surgery and, in the light of our successful practice, to contribute to
      the development of appropriate transfusion policies in Turkey. METHODS: In this
      study 1,811 female patients who underwent orthopedic elective or emergency
      surgery from January 1997 to December 1999 (group 1) and from January 2000 to
      December 2002 (group 2) were retrospectively evaluated with respect to ordered
      and transfused blood units. Autologous blood transfusions were not included.
      Group 1 consisted of 990 patients (mean age 50.4 years); group 2 consisted of 821
      patients (mean age 53.3 years). Maximum surgical blood order schedule (MSBOS)
      ratios and preference for red blood cell transfusions were determined.
      Perioperative target hemoglobin level was 10 gr /dL in both groups. In group 2,
      allogeneic blood transfusions were performed according to the principles
      established in January 2000, which aimed (i) to more precisely estimate blood
      loss during surgical procedures and to prevent inappropriate use of blood
      products; (ii) to reduce the frequency of "standard one unit transfusion" through
      administration of crystalloids and colloids to the extent of complete elimination
      of transfusions; and (iii) to use blood components (erythrocyte suspensions)
      instead of whole blood. RESULTS: In both groups, the MSBOS ratios were below 2,
      being 1.83 in group 1, and 1.59 in group 2. The medians of requested and
      transfused blood units were 2 and 1 in group 1, and 3 and 2 in group 2,
      respectively, resulting in statistically significant differences (p<0.05). The
      "standard one unit transfusion" rate was 28.7% in group 1, and 18.9% in group 2.
      Preferences for red blood cell transfusions showed statistically significant
      increases over the consecutive years. The use of erythrocyte suspensions was
      found as 29.2% in group 1, and 95% in group 2. CONCLUSION: Our data demonstrated
      that the transfusion policy established for orthopedic surgical procedures at our
      center resulted in successful applications thanks to a good cooperation between
      relevant departments and achieved the level of international standards.

PMID- 14578654
TI  - [The accuracy of references in Turkish journals in orthopedics and traumatology].
AB  - OBJECTIVES: The accuracy of references was assessed in Turkish journals of
      orthopedics and traumatology. METHODS: All references cited in four journals
      (Acta Orthopaedica et Traumatologica Turcica, Arthroplasty Arthroscopic Surgery,
      Hacettepe Journal of Orthopaedic Surgery, and The Journal of Turkish Spinal
      Surgery) throughout 1995 to 1999 were numbered consecutively. One percent of
      references from each journal was randomly selected to be evaluated in comparison
      with primary sources. Errors were classified in three categories. Another
      randomized selection was made to check 50 references from each journal. The
      results were assessed by the t-test. RESULTS: Of 18,193 references cited in four
      journals, 182 references were checked. Errors were found in 117 references (63%),
      seven of which were major errors that prevented location of the primary source.
      When 50 references were checked from each journal, the mean inaccuracy rate was
      60%. No significant differences were found between the journals with respect to
      the frequency of erroneous references. CONCLUSION: The high rate of inaccuracy
      emphasizes the need for greater care in the use of references on the part of
      authors, journal editors, and reviewers.

PMID- 14578655
TI  - [Doxorubicin-induced chemomyectomy effects in rat skeletal muscle].
AB  - OBJECTIVES: This study was based on the assumption that decreased number of
      active muscle fibres in the spastic muscle may be associated with restoration of
      the balance. Hence, the effect of doxorubicin was evaluated in inducing permanent
      cell necrosis on skeletal muscle (chemomyectomy). METHODS: Eighteen Wistar rats
      were divided into two groups, equal in size, to receive doxorubicin injections
      (0.02 and 0.05 mg/0.5 ml) into the left quadriceps muscles under general
      anaesthesia. The right quadriceps muscles (controls) were assigned to receive 0.5
      ml of physiologic saline solution. Three rats in each group were sacrificed on
      the 1st, 6th, and 10th post-injection weeks, after which all the quadriceps
      muscles were histologically evaluated. RESULTS: Histopathologic findings were
      normal in the control muscles. Dose-dependent acute inflammatory reactions were
      observed in both groups at the end of the first week, with a higher severity at
      0.05 mg doses. The size of the inflammation areas were 2.5% and 10% at 0.02 mg
      and 0.05 mg doses, respectively. At the end of six weeks, acute inflammatory
      reactions were replaced by the development of regeneration and fibrosis
      accounting to 0.8% of all the areas, regardless of the dose given. Specimens of
      the 10th week exhibited no regeneration; there was a mean of 2.5% fragmentation
      within the impaired areas, with atrophic fibrils and marked fibrosis showing no
      dose-dependence. CONCLUSION: Doxorubicin induces a dose-dependent inflammatory
      reaction during the early postoperative period. In the long-term, permanent
      effects, which are not dose-dependent, are observed characterized by
      fragmentation, atrophy, fibrosis of muscle fibres, and losses in contractile
      muscle elements. These doxorubicin-induced chemomyectomy effects may prove
      therapeutic in the treatment of spasticity-associated diseases.

PMID- 14578656
TI  - [Radiologic and morphologic evaluation of the lateral sacral mass].
AB  - OBJECTIVES: Morphologic measurements of the lateral sacral mass (LSM) and
      adjacent bone structures were made on dried sacrum specimens, together with
      radiologic evaluations on computed tomography (CT) scans in order to assess the
      appropriateness of this area in iliosacral screw applications. METHODS: On thirty
      dried human sacral bone specimens, morphologic measurements of the LSM were made
      by a compass sensitive to millimeters. Computed tomographic views of S1 and S2
      pedicle-bodies and intervertebral foramina were obtained to make radiologic
      measurements by a millimeter-sensitive ruler to examine the relationship between
      LSM and the neural canal and intervertebral foramina. RESULTS: The average widths
      of the LSM on the posterior and anterior surfaces of the sacrum were as follows.
      Posterior aspect: 24.1 mm on S1, 18.4 mm on S2 levels on the right; 24.5 mm on S1
      and 18.8 mm on S2 levels on the left. Anterior aspect: 28.9 mm on S1, 22.6 mm on
      S2 levels on the right; 29.1 mm on S1 and 23 mm on S2 levels on the left. The
      average (oblique) heights of LSM on the postero-lateral surface were 39 mm on S1,
      28.6 mm on S2 levels on the right; 37.4 mm on S1, 27.6 mm on S2 levels on the
      left. The average depth of the sacral ala was 50.6 mm on the right, 50.7 mm on
      the left. The average posterior alar height was 26 mm on both sides. On CT scans,
      the average widths of pedicle+sacral ala were measured as 37.6 mm (right) and
      36.3 mm (left) at the S1 pedicle-body level. The average widths of LSM were 22 mm
      (right) and 22.3 mm (left) at the S1 intervertebral foramina level. The average
      widths of pedicle+LSM were 27.8 mm (right) and 26.4 mm (left) at the S2 pedicle
      body level. The average widths of LSM at the S2 intervertebral foramina level
      were 15.9 mm (right) and 16.3 mm (left). CONCLUSION: Our results suggest that
      iliosacral screw fixation may be more safely performed, especially at the S1
      pedicle-body level and lateral to the sacral neural canal and intervertebral
      foramina. Injury to the neural tissues and surrounding structures is more
      unlikely if preoperative measurements of LSM are made on CT scans.

PMID- 14578657
TI  - [Avulsion fracture of the anterior superior iliac spine in a volleyball player].
AB  - Avulsion fractures of the apophyses of the pelvis rarely occur in adolescent
      athletes as a result of sudden and strong contraction of the muscles attached to
      the growth cartilage. We present a 16-year-old male patient who had an avulsion
      fracture of the left anterior superior iliac spine while he was playing
      volleyball. He presented with complaints of pain in the left hip and difficulty
      in walking. The diagnosis was made by means of pelvis x-rays, computed
      tomography, and three-phase radionuclide bone imaging. He underwent conservative
      treatment with a non-steroidal anti-inflammatory drug and bed rest. After two
      weeks, ambulation with crutches was allowed. At the end of four weeks, he was
      able to walk without crutches. He returned to his preinjury level of sports
      activities at the end of six weeks, without any complaint of pain.

PMID- 14578658
TI  - [Ankylosis of the spine in a case with ochronosis].
AB  - A thirty-nine-year-old man presented with a complaint of low back pain with a
      history of 20 years. Cervical and thoracolumbar radiographs showed wide
      calcification areas and ankylosis in the intervertebral discs. Observation of
      blue-gray pigmentation around his nose and ears suggested a diagnosis of
      ochronosis, which was confirmed by the detection of high levels of homogentisic
      acid in the urine and dark urine color following alkalization. Ochronosis should
      be included in the differential diagnosis in patients with chronic low back pain,
      calcified intervertebral discs, and black pigmentation in cartilagenous and
      collagenous tissues.

PMID- 14578659
TI  - [The course of historical development of treatment approaches to rotator cuff
      related problems].
AB  - Rotator cuff-related issues and problems first appeared in the medical literature
      in the eighteenth century. A significant amount of knowledge was obtained on
      diagnosis and treatment over the twentieth century, most of which is the result
      of pioneering work of Codman and Neer. In this review, a chronological course of
      development is tracked to better understand future venues.

PMID- 14578660
TI  - [Anatomy, biomechanics, and physiopathology of the rotator cuff].
AB  - Rotator cuff disease is the most common cause of shoulder pain and dysfunction in
      adults. Despite the significant amount of pain and disability related to rotator
      cuff pathology, there is insufficient information to guide the clinician in
      planning therapeutic interventions. In this article, we reviewed the anatomy,
      biomechanics, and pathophysiology of the rotator cuff in an attempt to cover
      recent literature thereof. A consensus is now emerging that the etiology of
      rotator cuff disease is multifactorial, including extrinsic and intrinsic
      factors. Further investigations are needed to clarify the mechanisms and the
      pathogenesis of rotator cuff disease, as well as the effectiveness of various
      treatment modalities.

PMID- 14578661
TI  - [Diagnostic imaging of the rotator cuff].
AB  - The importance of imaging modalities in the evaluation of the rotator cuff has
      increased thanks to the development of non-invasive methods. An optimum
      application of the technique, appreciation of the anatomical details and imaging
      pitfalls, and proper interpretation of clinical findings should be incorporated
      in order to increase diagnostic accuracy. Ultrasonography (US) and magnetic
      resonance imaging (MRI) are commonly used for rotator cuff pathologies. The
      former has a high diagnostic accuracy in full-thickness tears, but requires
      operator dependency and long-term training. Both US and MRI require sophisticated
      equipment and present difficulties in distinguishing between partial and small
      full-thickness tears. In full-thickness tears, MRI may be more appropriate if
      imaging findings are likely to alter the course of surgical treatment. However,
      it is not necessary in patients in whom US may clearly show tendinosis. Magnetic
      resonance imaging or MR arthrography may be required in order to evaluate partial
      tears or suspicious small full-thickness tears in patients unresponsive to
      conservative therapy. A close collaboration is essential between the radiologist
      and the shoulder surgeon in the interpretation of clinical findings. The
      diagnostic accuracy will increase if the examinations are performed by a
      musculoskeletal radiologist.

PMID- 14578662
TI  - [Subacromial impingement syndrome: pathogenesis, clinical features, and
      examination methods].
AB  - Although subacromial impingement syndrome is the most common cause of shoulder
      pain with a specific diagnosis, it is not the only cause of pain in the
      anterosuperior aspect of the shoulder. Appreciation of the pathophysiology plays
      a key role in the diagnosis and management of this syndrome. The purpose of this
      paper is to review some essential aspects of pathogenesis, physical examination,
      and diagnosis in the light of the current literature.

PMID- 14578663
TI  - [The value of acromioplasty in the treatment of subacromial impingement
      syndrome].
AB  - Although acromioplasty is widely used in the treatment of subacromial impingement
      syndrome, there is some controversy about the role of acromion morphology in the
      etiology. The acromion and the coracoacromial ligament provide passive
      stabilization against upward migration of the humeral head and play an important
      role in shoulder biomechanics. This article discusses relevant issues on
      subacromial impingement syndrome pertaining to the acromion and the value of
      acromioplasty in the treatment.

PMID- 14578664
TI  - [Problems pertaining to the long head of the biceps brachii in subacromial
      impingement syndrome].
AB  - In this paper, we presented the pathological changes occurring in the long head
      of the biceps muscle in subacromial impingement syndrome, and evaluated treatment
      approaches in the light of the relevant data.

PMID- 14578665
TI  - [Open surgical techniques for subacromial impingement syndrome].
AB  - Various surgical techniques have been used for the treatment of subacromial
      impingement syndrome, ranging from complete acromionectomy to arthroscopic
      subacromial decompression. Following the recognition of the importance of the
      acromial arch in maintaining superior stability of the glenohumeral joint,
      attempts have been directed to minimize the amount of acromial excision. In this
      article, open surgical subacromial decompression techniques and the importance of
      the amount of acromial excision are discussed.

PMID- 14578666
TI  - [Arthroscopy of the shoulder: general principles and stages for promoting
      competence].
AB  - Arthroscopic surgery of the shoulder has replaced several open procedures because
      of minimal morbidity. However, like other joint arthroscopic procedures, it
      involves a significant learning curve. In addition, it requires availability of
      special equipment and certain operating conditions. It is advisable to achieve
      enhanced experience and competence in diagnostic arthroscopy and then to practice
      arthroscopic surgery in a staged manner. This review aims to provide an outline
      of current knowledge about general principles of shoulder arthroscopy, diagnostic
      arthroscopy, and arthroscopic surgical procedures.

PMID- 14578667
TI  - [Arthroscopic subacromial decompression in the treatment of impingement
      syndrome].
AB  - During the past decade, arthroscopy has become an accepted tool for the
      evaluation and management of shoulder disorders. The glenohumeral joint,
      subacromial space, acromioclavicular joint, and even the scapulothoracic
      articulation can be assessed through arthroscopy. Proper portal placement allows
      a safe access without risk for neurovascular, tendon, or articular injuries.
      Anterior acromioplasty is probably the most common arthroscopic procedure
      performed in the shoulder, with reported results similar to open techniques. This
      article focuses on the arthroscopic treatment of impingement syndrome in the
      light of published data, together with its technical aspects.

PMID- 14578668
TI  - [Classification of rotator cuff tears].
AB  - Classification of rotator cuff tears may yield useful information on diagnosis,
      treatment, prognosis, and evaluation of treatment results. The shape,
      localization, etiology, size, topography, pathology, and history of rotator cuff
      tears, together with the involvement of specific tendons in the occurrence of a
      tear may be of great value in the hand of expert interpreters. This article
      intends to give a brief description of rotator cuff tears by way of illustration.

PMID- 14578669
TI  - [Methods for fixation of the rotator cuff].
AB  - Rotator cuff repair has gained increasing popularity in recent years. Fixation of
      the tendon to the bone presents challenging difficulties like those in many parts
      of the human body. There is ongoing research concerning clinical and
      biomechanical features of open and arthroscopic repair methods, though
      accumulated evidence in the past years suggests that the latter may provide a
      more secure fixation. Considering the general advantages of arthroscopy, we may
      propose that arthroscopic rotator cuff repair with anchor fixation will gain more
      acceptance. This article reviews the most recent literature on the subject.

PMID- 14578670
TI  - [Massive rotator cuff tears: diagnosis and treatment techniques].
AB  - The treatment of massive rotator cuff tears presents challenging difficulties. Re
      rupture after treatment may be frequently seen, along with it muscular
      degeneration, leading to insufficient clinical results. There is still
      controversy as to whether conservative or surgical treatment methods will be more
      appropriate for massive and partial tears. This article aimed to provide an
      update on the diagnosis and treatment of massive rotator cuff tears.

PMID- 14578671
TI  - [All arthroscopic treatment of rotator cuff tears].
AB  - Although shoulder arthroscopy was initially performed solely for subacromial
      decompression, at present it is widely used for rotator cuff repairs and
      reconstruction. All arthroscopic rotator cuff repairs have been performed
      increasingly over the past decade and favorable long-term results have been
      reported in the literature. All arthroscopic rotator cuff repair has advantages
      over mini-open, or open rotator cuff repair, because it is associated with less
      postoperative pain and morbidity, and a more rapid improvement in shoulder
      motion. However, complete arthroscopic rotator cuff repair is a technically
      difficult procedure, with some limitations including relative weakness of tendon
      sutures and the need for more experience. It is essential that the merits and
      demerits associated with this technique should be balanced depending on the
      individual condition of the patient and the degree of experience gained. This
      article revisits all arthroscopic rotator cuff repair with regard to advantages
      and disadvantages, surgical techniques, indications, postoperative
      rehabilitation, and the results both in the light of the literature and our
      experience.

PMID- 14578672
TI  - [Arthroscopic capsular shrinkage for posterosuperior internal impingement of the
      shoulder].
AB  - OBJECTIVES: We evaluated clinical and radiological findings and functional
      results following arthroscopic capsular shrinkage in patients with internal
      impingement of the shoulder. METHODS: The study included four patients (2
      females, 2 males; mean age 27.5 years; range 25 to 32 years) who underwent
      arthroscopic capsular shrinkage between 1997 and 2001. Three patients were
      overhead athletes (2 volleyball, 1 water polo player), the fourth was a clerk.
      All the patients suffered from shoulder pain upon abduction and external rotation
      and all received a preoperative unsuccessful rehabilitation for at least three
      months (range 3 to 10 months). Following arthroscopic examination of the
      glenohumeral joint, anterior joint capsule was shrunk using a radiofrequency
      probe. A specific rehabilitation program was applied postoperatively. The mean
      follow-up was 3.5 years (range 2 to 6 years). RESULTS: The Neer test was positive
      in all cases, and the relocation test in 3 cases, preoperatively. Magnetic
      resonance imaging showed contact between the glenoid rim and the greater
      tuberosity in three cases, degeneration in the rotator cuff in two cases, a
      partial tear in one patient, and a subchondral cyst in another. Arthroscopic
      examination revealed glenoid-rotator cuff contact in all cases and degeneration
      in the contact areas. Drive-through sign was positive in all cases. Kissing
      lesion was present in one case. No SLAP lesion was identified. The patients'
      complaints disappeared and the three athletes were able to resume their
      professional sporting activities. CONCLUSION: Arthroscopic shrinkage of the
      stretched anterior capsule proved successful throughout a follow-up period of at
      least two years.

PMID- 14578673
TI  - [Conservative treatment of subacromial impingement syndrome].
AB  - Impingement syndrome affects a wide range of active population with various
      pathologies and presentations. Symptoms include pain, weakness, and loss of
      motion. Causes of impingement include acromioclavicular joint arthritis,
      calcified coracoacromial ligament, structural abnormalities of the acromion, and
      weakness of the rotator cuff muscles. Conservative treatment (rest, ice packs,
      non-steroidal anti-inflammatory drugs and physical therapy) is usually
      sufficient. This paper evaluated some conservative treatment programmes.

PMID- 14578674
TI  - [Rehabilitation following anterior acromioplasty].
AB  - The shoulder region is one of the most challenging part of the human body to
      rehabilitate. Postoperative days following anterior acromioplasty are painful,
      with a high potential course of developing soft tissue fibrosis and joint
      contracture. In the past, following anterior acromioplasty and/or rotator cuff
      repair, the rehabilitation process was usually delayed for up to four to six
      weeks to allow healing of the repaired site. This conservative rehabilitation
      approach resulted in significant restrictions in glenohumeral and scapular joint
      mobility, weakness of the shoulder girdle musculature, prolonged pain, and
      functional limitations. Currently the trend of rehabilitation following anterior
      acromioplasty shifted toward a more earlier and aggressive approach thanks to
      improved surgical and soft tissue fixation techniques and advances in
      arthroscopic procedures. This has allowed active-assisted shoulder motion
      immediately after subacromial decompression and rotator cuff surgery. The
      rehabilitation team following anterior acromioplasty of the shoulder should
      consist of the physiatrist, orthopedic surgeon, physical therapist, and the
      patient.

PMID- 14578675
TI  - [Subacromial impingement syndrome in athletes: prevention and exercise programs].
AB  - The shoulder joint, the most mobile joint in the human body, is at greater risks
      for injuries. Several factors contribute to shoulder impingement syndrome
      including rotator cuff weakness, capsular tightness, poor scapulohumeral rhythm,
      and muscle imbalance of the scapular upward rotation force couple. Rehabilitation
      and training of the shoulder in throwing and overhead athletes has dramatically
      improved during the last decade. There are numerous reasons for rapid return to
      athletic training and competition. A preventive program designed for the
      glenohumeral joint is mainly based on an appropriate preparation, which should
      include overall body conditioning, flexibility, and strengthening of the
      musculature around the glenohumeral joint and the scapula. Activity levels
      represent a helpful guide in determining an appropriate rehabilitation program
      for shoulder patients ranging from disabled to those competing at the highest
      levels of athletics. This article discusses issues related to prophylactic
      measures, non-operative treatment, postoperative treatment, and rehabilitation
      programme of impingement syndrome in athletes.

PMID- 14578676
TI  - The mechanism of action of docetaxel (Taxotere) in xenograft models is not
      limited to bcl-2 phosphorylation.
AB  - Docetaxel is a new taxoid compound with a broad spectrum of antitumor activity.
      Previous studies have shown that in vitro treatment of specific human tumor lines
      with docetaxel is associated with the phosphorylation and inactivation of the bcl
      2 protein and the occurrence of apoptosis. The goal of this study was to examine
      whether bcl-2 expression is truly required for in vivo responsiveness to
      docetaxel. The expression and state of phosphorylation of bcl-2 was examined in
      human MX-1 breast or DU-145 prostate tumors explanted from nu/nu mice treated
      with docetaxel. The MX-1 cells accumulated in the G2/M phase of the cell cycle
      and exhibited phosphorylation of bcl-2 after treatment with docetaxel. By Western
      blot analysis DU-145 prostate tumor cells did not express bcl-2 protein before or
      following in vivo treatment with docetaxel. However, docetaxel was highly active
      against the DU-145 tumor xenograft model. Thus, docetaxel induces apoptosis and
      cell death through a different, bcl-2-independent mechanism in the DU-145 human
      prostate tumor, indicating that bcl-2 may not have prognostic value for treatment
      with docetaxel.

PMID- 14578677
TI  - The alkylating agent penclomedine induces degeneration of purkinje cells in the
      rat cerebellum.
AB  - PURPOSE: Penclomedine (PEN), a multichlorinated alpha-picoline derivative which
      is metabolized to highly reactive alkylating species, was selected for clinical
      development due to its prominent activity against a wide range of human tumor
      xenografts when administered either parentally or orally. Its principal dose
      limiting toxicity in preclinical and clinical studies has been neurocerebellar
      toxicity, which has been related to the magnitude of peak plasma PEN
      concentrations, but not to plasma concentrations of its putative principal
      alkylating metabolite, 4,o-demethylpenclomedine (DMPEN). These observation, as
      well as PEN's toxicologic, pharmacologic, and tissue distribution profiles, have
      suggested that the parent compound is primarily responsible for cerebellar
      toxicity. The studies described in this report were undertaken to characterize
      the neuropathology of PEN neurotoxicity, with a long-term goal of developing
      strategies to maximize its therapeutic index. DESIGN: Male Sprague-Dawley rats
      were treated with therapeutically relevant doses of PEN, orally and
      intraperitoneally (i.p.), on various administration schedules, and DMPEN
      administered i.p. The animals were monitored for neurotoxicity, and brain
      sections were examined for neuropathology, particularly Purkinje cell loss and
      neuronal injury. Brain sections were stained using standard histochemical
      techniques and immunostained with OX-42 to detect microglial cells that are
      activated following neuronal damage, and calbindin D(28K), a calcium-binding
      protein expressed by cerebellar Purkinje cells. RESULTS: Dose-related
      neurocerebellar toxicity associated with parasagittal bands of Purkinje cell
      degeneration and microglial activation in the cerebellar vermis were evident in
      rats treated with PEN 100-400 mg/kg i.p. as a single dose. Neuronal injury was
      not observed in other regions of the brain. Furthermore, neither clinical nor
      histopathological evidence of cerebellar toxicity was apparent in rats treated
      with similar total doses of PEN administered i.p. on a dailyx5-day dosing
      schedule. Similar histological findings, in an identical neuroanatomical
      distribution, were observed in rats treated with PEN orally; however, the
      magnitude of the neuronal toxicity was much less than in animals treated with
      equivalent doses of PEN administered i.p. Although acute lethality occurred in
      some rats treated with equimolar doses of DMPEN as a single i.p. treatment,
      surviving animals exhibited neither signs nor histopathological evidence of
      neurocerebellar toxicity. CONCLUSIONS: PEN produces selective dose- and schedule
      dependent Purkinje cell degeneration in the cerebellar vermis of rats, whereas
      therapeutically relevant doses of PEN administered orally are better tolerated
      and produce less neurocerebellar toxicity. In addition, roughly equivalent,
      albeit intolerable, doses of the major active metabolite DMPEN, which was lethal
      to some animals, produced neither clinical manifestations of neurocerebellar
      toxicity nor Purkinje cell loss. These results support a rationale for
      investigating whether PEN administered orally, which may undergo significant
      first-pass metabolism to DMPEN and other less toxic intermediates, or treatment
      with DMPEN, itself, may result in less neurocerebellar toxicity and superior
      therapeutic indices than PEN administered parenterally.

PMID- 14578679
TI  - Effect of valspodar on the pharmacokinetics of unbound paclitaxel.
AB  - The aim of this multicenter study was to determine whether valspodar (Amdray;
      code designation, SDZ PSC 833), a potent P-glycoprotein (P-gp) inhibitor, affects
      the pharmacokinetics of unbound paclitaxel (Cu). Data were obtained from 31
      patients with advanced breast cancer. Thirteen patients were treated with
      paclitaxel alone (3-h infusion at 175 mg/m2) and another 18 received paclitaxel
      (3-h infusion at 70 mg/m2) in combination with a 21-day cycle of oral valspodar
      (5 mg/kg given four times a day) starting 1 day before administration of
      paclitaxel. Serial blood samples were taken in the first course and Cu in plasma
      determined using equilibrium dialysis with a [G-3H]paclitaxel tracer. The
      apparent clearance of Cu was not significantly different between the two groups,
      with mean +/- standard deviation (+/- SD) values of 230 +/- 56.0 and 202 +/- 49.9
      L/h/m2 in the absence and presence of valspodar, respectively (P = 0.17). The
      volume of Cu distribution was slightly larger in the presence of valspodar (1160
      +/- 474 vs. 1620 +/- 552 L/m2; P = 0.025), which contributed to a minor
      difference in the terminal disposition half-life (6.12 +/- 3.42 vs. 8.50 +/- 2.06
      h; P = 0.028). These data indicate that (i) valspodar lacks the significant
      interaction with paclitaxel observed previously with other P-gp modulators, (ii)
      the majority of the increased toxicity of the combination does not appear to be
      attributable to increased levels of Cu, and (iii) provide further evidence of the
      conjecture that the plasma concentration of paclitaxel may not be an appropriate
      measure to monitor the impact of P-gp inhibition.

PMID- 14578678
TI  - Immunomodulatory effects of docetaxel on human lymphocytes.
AB  - Docetaxel is an antineoplastic taxoid that interferes with microtubule
      polymerization dynamics and is used clinically to treat advanced cancers. Because
      microtubules play significant roles in T lymphocyte activation and function we
      characterized the in vitro immunomodulatory properties of docetaxel. Effects of
      docetaxel on lectin-induced peripheral blood mononuclear cell (PBMC)
      proliferation were measured by the 3-(4,5-dimethylthiazol-2-yl)-5-(3
      carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay and
      proliferating cell nuclear antigen (PCNA) staining. In addition, apoptosis was
      measured by annexin V staining and cell activation by determination of CD25 and
      CD71 cell surface expression. Intracellular calcium kinetics in lectin-activated
      Jurkat T lymphocytes exposed to docetaxel were investigated. Th1 cytokine
      production was assessed in T lymphocytes by intracellular cytokine staining.
      Docetaxel significantly inhibited PBMC proliferation and promoted apoptosis of
      lectin-activated PBMCs. Docetaxel significantly decreased expression of CD71 but
      not that of CD25. Docetaxel altered intracellular calcium homeostasis but did not
      affect Th1 cytokine production in T lymphocytes. In conclusion we demonstrate
      that docetaxel, although exerting significant antiproliferative effects on
      lymphocytes and promoting activation-induced apoptosis does affect only partially
      lymphocyte activation and function and does not affect Th1 cytokine production.
      These results suggest maintenance of lymphocyte functions important for host
      tumor surveillance and suggest that this compound may have a role in the
      treatment of cancer arising organ transplant recipients.

PMID- 14578680
TI  - Phase I studies of weekly administration of cytotoxic agents: implications of a
      mathematical model.
AB  - Certain toxic effects of cytotoxic anticancer agents typically evolve over weeks.
      When such agents are administered weekly, these effects are cumulative. With such
      schedules, good medical practice mandates dose modifications with mild or
      moderate toxicity in order to avoid progression to serious or life-threatening
      toxicity. These modifications lead to differences between scheduled and delivered
      doses. Phase I studies are designed to identify the maximum tolerated dose for a
      given schedule. Yet neither standard phase I study designs nor the theoretical
      literature acknowledge the existence or incorporate the impact of dose
      modifications upon phase I study outcomes. Our purpose was to better understand
      the impact of dose reductions/omissions upon outcomes of phase I studies of
      weekly administration of cytotoxic agents. We created a mathematical model in
      which toxicity was represented as a power function of dose in order to represent
      extremes of behavior observed with actual cytotoxic agents in the clinic. We used
      the model to simulate dosing and toxicity experiences across a wide range of
      doses. From these simulations we identified "best doses" according to a variety
      of traditional and novel criteria. We find the concept of maximum tolerated dose
      inadequate for the determination of best doses. We also suggest a strategy for a
      new phase I study design which can be used to estimate the "best dose"
      corresponding to a specified delivery rate. In summary, identification of best
      doses requires attention, not only to dose limiting toxic events, but also to
      delivered dose rates and schedule adherence.

PMID- 14578682
TI  - Phase II trial of ZD1839 (IRESSA) in patients with advanced renal cell carcinoma.
AB  - Eighteen patients with advanced renal cell carcinoma (RCC) were treated on a
      phase II trial with ZD1839 (IRESSA). Treatment efficacy was determined using the
      endpoint of improvement in time to progression (TTP) compared to TTP in patients
      who received interferon-alpha therapy. The Memorial Sloan Kettering Cancer Center
      database of renal cell patients shows that patients receiving therapy with
      interferon-alpha had a median TTP of 4.7 months, with 40% of patients having
      disease progression at 4 months. To show efficacy in this trial, 60% of evaluable
      patients would have to remain progression free at 4 months. Treatment with ZD1839
      did not result in any complete or partial responses, and 13 patients (81%) had
      progression of disease within 4 months of start of therapy. At the dose and
      schedule used in this trial, the lack of antitumor activity associated with
      ZD1839 does not support further study in patients with metastatic RCC.

PMID- 14578683
TI  - Phase II study of XR5000 (DACA), an inhibitor of topoisomerase I and II,
      administered as a 120-h infusion in patients with advanced ovarian cancer.
AB  - BACKGROUND: XR5000 is a tricyclic carboxamide-based cytotoxic agent that binds to
      DNA by intercalation and stimulates DNA cleavage by inhibition of both
      topoisomerase I and II. The aim of the present study was to evaluate the
      antitumoral activity and safety profile of XR5000 given as second-line
      chemotherapy in patients with ovarian cancer who had relapsed within 1 year after
      first-line chemotherapy with taxanes and platinum for advanced disease. PATIENTS
      AND METHODS: Patients received XR5000 at the dose of 3010 mg/m(2) through a 120-h
      central venous infusion every 3 weeks. Toxicity was graded according to the
      Common Toxicity Criteria (CTC), version 2.0. An independent panel assessed
      response every two cycles according to the World Health Organization (WHO)
      criteria. Gehan's rule was used for sample size determination. RESULTS: Sixteen
      patients were enrolled; one patient was ineligible because of prior melphalan
      single agent treatment. Eastern Cooperative Oncology Group (ECOG) performance
      status was 0 (eight patients), 1 (five patients), or 2 (two patients). The 15
      eligible patients received 43 cycles of XR5000 (median 2, range 1-8).
      Hematological toxicity was mild with only one grade 3 anemia in one patient.
      Other drug-related toxicities never exceeded grade 3 and included fatigue (four
      patients), thrombosis (one patient), nausea (one patient), stomatitis (one
      patient) as well as dyspnea/cough (one patient). One patient who had refused
      further therapy and controls after the first cycle was not assessable for
      response evaluation. No objective responses were observed. Four patients
      experienced stable disease and 10 patients progressive disease. The median time
      to progression was 42 days (CI 95% 40; 54). CONCLUSIONS: The complete lack of any
      objective response does not justify further evaluation of XR5000 in patients with
      advanced ovarian cancer using this dose and schedule, although the therapy was
      generally well tolerated.

PMID- 14578681
TI  - Positron emission tomography (PET): expanding the horizons of oncology drug
      development.
AB  - Positron emission tomography (PET) allows three-dimensional quantitative
      determination of the distribution of radioactivity permitting measurement of
      physiological, biochemical, and pharmacological functions at the molecular level.
      Until recently, no method existed to directly and noninvasively assess transport
      and metabolism of neoplastic agents as a function of time in various organs as
      well as in the tumor. Standard preclinical evaluation of potential anticancer
      agents entails radiolabeling the agent, usually with tritium or 14C, sacrifice
      experiments, and high-performance liquid chromatography (HPLC) analysis to
      determine the biodistribution and metabolism in animals. Radiolabeling agents
      with positron-emitting radionuclides allows the same information to be obtained
      as well as in vivo pharmacokinetic (PK) data by animal tissue and plasma sampling
      in combination with PET scanning. In phase I/II human studies, classic PK
      measurements can be coupled with imaging measurements to define an optimal dosing
      schedule and help formulate the design of phase III studies that are essential
      for drug licensure [1]. Many of the novel agents currently in development are
      cytostatic rather than cytotoxic and therefore, the traditional standard
      endpoints in phase I and II studies may no longer be relevant. The use of a
      specialized imaging modality that allows PK and pharmacodynamic (PD) evaluation
      of a drug of interest has been proposed to permit rapid and sensitive assessment
      of the biological effects of novel anticancer agents. The progress to date and
      the challenges of incorporating PET technology into oncology drug development
      from the preclinical to clinical setting are reviewed in this article.

PMID- 14578684
TI  - A phase II trial of pemetrexed in patients with metastatic renal cancer.
AB  - BACKGROUND: Metastatic renal cell carcinoma (RCC) is rising in incidence but
      remains difficult to treat. This clinical trial evaluated the effects of
      pemetrexed (multitargeted antifolate, ALIMTAR) for the treatment of metastatic
      RCC. PATIENTS AND METHODS: Patients were required to have histological diagnosis
      of metastatic RCC with measurable disease and no prior chemotherapy. In addition,
      patients were required to have a World Health Organization (WHO) performance
      status of 0-2 and adequate bone marrow reserve. Patients received pemetrexed at a
      dose of 600 mg/m2 as a 10 min infusion every 3 weeks. Patients did not receive
      folic acid or vitamin B12 supplementation. RESULTS: Thirty-nine patients were
      enrolled and thirty two were evaluable for response. Three patients had a partial
      response for a response rate of 9% (95% CI 2-25%). The median time to progressive
      disease was 10.5 months. Of the nonresponders, twenty two had stable disease
      (median duration was 5.8 months; range 1.5-27.7) and seven had progressive
      disease (median time to progression was 5.4 months). Median time to progression
      for all qualified patients was 5.7 months. Common toxicities experienced were
      diarrhea and infection. Fatigue, stomatitis, and rash were also reported. The
      most common hematologic toxicity was grade 3/4 lymphopenia in 76% of patients.
      Leukopenia, granulocytopenia, and thrombocytopenia were also frequently reported.
      CONCLUSION: Single-agent pemetrexed has moderate activity in the treatment of
      metastatic RCC and should be investigated in combination with other potential
      active agents, as first-line treatment.

PMID- 14578685
TI  - Phase II trial and pharmacokinetic study of thalidomide in patients with
      metastatic colorectal cancer.
AB  - INTRODUCTION: This study was designed to estimate the percentage of objective
      tumor responses, toxicity profile, and obtain additional information about the
      plasma pharmacokinetics of thalidomide in patients with refractory and
      progressing metastatic colorectal cancer. STUDY DESIGN: This phase II clinical
      trial was conducted according to the two-stage Simon method with the inclusion of
      consecutive patients. The study protocol was approved by the Institutional Review
      Board (IRB) of the Academic Hospital (HCPA) of the Federal University of Rio
      Grande do Sul (UFRGS), Porto Alegre, Brazil. PATIENTS AND METHODS: Seventeen
      patients with previously treated, refractory progressive metastatic colorectal
      cancer were eligible. Six patients had prior radiotherapy. The patients had a
      median of one previous chemotherapy regimen. Patients were initially treated with
      200 mg/day of thalidomide with an increase in dose by 200 mg/day every 2 weeks
      until a final daily dose of 800 mg/day was achieved. Patients were evaluated
      every 8 weeks for response by radiographic criteria. Plasma pharmacokinetics
      studies were performed in four patients at 200 mg level and in one patient at 600
      mg during the first 24 h. MAIN OUTCOME MEASURES AND RESULTS: A total of 17
      patients were accrued, all of them being evaluable for toxicity and 14 for
      response. Thalidomide was well tolerated, with constipation, somnolence,
      dizziness, and dry mouth being the major toxicities. There were no objective
      response or stable disease. The median survival was 3.6 months. Single-agent
      thalidomide is a generally well-tolerated drug that showed no antitumor activity
      in patients with advanced pretreated metastatic colorectal cancer. Although
      thalidomide did not show antitumor activity in this patient population, future
      studies of this agent in patients at initial stages of the disease (when its
      antiangiogenic properties may be more relevant to disease progression) could be
      considered.

PMID- 14578686
TI  - Phase II trial of perillyl alcohol (NSC 641066) administered daily in patients
      with metastatic androgen independent prostate cancer.
AB  - OBJECTIVE: We conducted a phase II multicenter trial of perillyl alcohol in
      patients with advanced hormone refractory prostate cancer (HRPC). The primary
      endpoint was to evaluate the 6-month progression-free survival given the
      potential cytostatic nature of the drug. Secondary objectives included assessing
      acute and chronic toxicities, as well as measuring objective response rates.
      METHODS: Patients with metastatic androgen-independent prostate cancer that
      failed at least one prior chemotherapeutic or experimental regimen were eligible.
      Perillyl alcohol was administered orally at 1200 mg/m2/dose four times daily and
      continued until disease progression or development of unacceptable toxicity.
      RESULTS: Fifteen patients were eligible. Six patients received less than one
      cycle (4 weeks) of drug, four of which stopped because of drug intolerance. Only
      six patients received more than two cycles of therapy and were considered
      evaluable for response. Main toxicity included grade 1-2 gastrointestinal
      intolerance (nausea/vomiting in 60% of the patients) and fatigue (47%). One
      patient developed a grade 4 hypokalemia that was felt likely attributable to the
      drug. No objective responses were seen. All patients either progressed or
      withdrew from the study secondary to drug intolerance before the 6-month time
      period. CONCLUSION: Perillyl alcohol administered at this dose and formulation
      did not have any objective clinical activity in this patient population.

PMID- 14578687
TI  - A randomized phase II evaluation of bryostatin-1 (NSC #339555) in recurrent or
      persistent platinum-sensitive ovarian cancer: a Gynecologic Oncology Group Study.
AB  - OBJECTIVES: The Gynecologic Oncology Group (GOG) performed a randomized phase II
      study to determine the antitumor activity and toxicity of two different schedules
      of bryostatin-1 administration in patients with recurrent or persistent platinum
      sensitive epithelial ovarian cancer or primary peritoneal carcinoma. METHODS:
      Eligible patients were randomized to receive either bryostatin-1 25 microg/m2 as
      a 1h infusion weekly for 3 weeks followed by a 1-week rest (Regimen I) or
      bryostatin-1 120 microg/m2 as a 72 h continuous infusion every 2 weeks (Regimen
      II). RESULTS: Fifty-five patients were enrolled on this study. There was one
      durable response among 27 eligible patients (response rate=3.7%) on Regimen II
      and no responses in the 27 eligible patients on Regimen I. Nineteen patients
      (eleven on Regimen I and eight on Regimen II) had stable disease. The most common
      adverse event was myalgia, with 12 of 27 patients (44%) on each regimen
      experiencing some degree of myalgia. There were no other significant toxicities
      on either treatment arm. CONCLUSIONS: Both of these schedules and doses of
      bryostatin-1 are inactive as single agents in previously treated epithelial
      ovarian cancer.

PMID- 14578688
TI  - IT integration transforms the care continuum.

PMID- 14578691
TI  - Four-year follow-up study of sleep and psychiatric symptoms in preadolescents:
      relationship of persistent and temporary sleep problems to psychiatric symptoms.
AB  - The course of sleep disturbances in preadolescents was assessed during a 4-year
      follow-up, and psychiatric problems associated with persistent and temporary
      sleep problems were investigated in an epidemiological setting. A representative
      random sample of 1,290 children, their parents, and school teachers filled out
      various questionnaires when the children were aged 8 and 12 years. Response rates
      to the relevant items varied between 66.8% and 81.2%. Parental reports of sleep
      problems decreased from 23.4% to 9.1% during the 4-year period, whereas
      children's reports remained steady at 18%. Persistent sleep disturbances were
      found in 12% of children, and 33.3% of sleep problems reported at age 8 were
      continued. Both current and persistent sleep disturbances were associated with
      the broad range of mental health problems reported by teachers. However,
      multivariate modeling suggested that especially current sleep problems were
      associated with an increased risk for psychiatric problems (odds ratio [OR] 2.45;
      95% confidence interval [CI] 1.20-4.99), particularly emotional problems (OR
      2.92; 95% CI 1.58-5.38).

PMID- 14578692
TI  - Parental opinions regarding treatment for social anxiety disorder in youth.
AB  - This study surveyed parents' opinions about treatment for childhood social
      anxiety disorder and assessed variables that may affect treatment acceptability.
      A 20-item survey assessing treatment attitudes and a semistructured interview
      were administered to 190 parents of children (8-17 years) who were randomly
      selected from a pediatric primary care setting. An exploratory factor analysis of
      the treatment attitudes survey yielded four factors: medication acceptability,
      counseling acceptability, counseling feasibility, and general beliefs about
      social anxiety treatment. Findings revealed that parents endorsed favorable
      attitudes toward counseling and somewhat neutral beliefs about medication. White
      parents were more accepting of medication and counseling and also perceived
      counseling as more feasible than nonwhite parents. Treatment acceptance was
      associated with past mental health utilization but not with severity of social
      anxiety. Further research is necessary to determine if clinical interventions for
      child anxiety disorders may be more efficacious if parents' attitudes and beliefs
      about prescribed treatments are addressed.

PMID- 14578693
TI  - Developmental trajectories of cocaine-and-other-drug-exposed and non-cocaine
      exposed children.
AB  - Few data are available concerning the trajectories of mental and motor
      development across time for cocaine-exposed children compared with others.
      Findings are presented from individual group curve analyses of the mental and
      motor development measured by the Bayley Scales of Infant Development-II (BSID
      II) on repeated visits from 3 through 36 months of a group of prenatally cocaine
      and-other-drug-exposed children (n = 265) compared with those exposed to no drugs
      (n = 129) or no-cocaine-but-other-drugs (n = 66), including alcohol and/or
      tobacco. Across time, there was a general decline in motor performance but
      cocaine-exposed-infants showed a trend toward a greater decrease than children in
      the other two comparison groups. For mental performance, there was also a decline
      across age but only through 24 months and no differences in the trajectory of the
      cocaine-exposed group compared to the other two. And, across all assessment ages,
      cocaine-exposed-infants showed lower BSID-II mental performance compared to both
      non-drug and non-cocaine-exposed children. Results suggest that prenatally
      cocaine-exposed children show delayed developmental indices, particularly in
      their mental performance, but their trajectories across time are similar to those
      from impoverished, non-cocaine-exposed groups.

PMID- 14578694
TI  - Emotion self-regulation in preschool-aged children with and without orofacial
      clefts.
AB  - Emotion self-regulation is an important developmental task in the preschool
      period that is related to children's emotional and behavioral adjustment in early
      childhood. Emotion self-regulation and its relation to later adjustment has not
      been studied in children born with orofacial clefts, despite their risk for
      externalizing and internalizing behavior problems. Eighty-three 5-year-old
      children with cleft lip and palate, isolated cleft palate, or no cleft condition
      were videotaped during a laboratory disappointment situation. Results showed that
      children in the cleft group expressed less disappointment than children in the
      comparison group. Longitudinal analyses revealed that parenting stress measured
      when the children were 2 years of age predicted Expressed Disappointment at age 5
      years, which, in turn, predicted severity of behavior problems at age 7 years.
      Although tentative, results indicate that control over mild negative affect may
      be a protective factor for children with clefts, buffering the effects of early
      stress on the development of later behavioral and emotional problems. Thus,
      interventions that reduce parenting stress and enhance children's emotion
      regulation strategies may decrease the risk for later psychological problems in
      this population.

PMID- 14578695
TI  - Inhibitory motor control at five years as a function of prenatal cocaine
      exposure.
AB  - This study examined children's (n = 140, age 5 years) ability to inhibit a motor
      response as a function of prenatal cocaine exposure. We hypothesized that cocaine
      exposed children would perform worse than unexposed children on the Contrary
      Tapping task. Results indicated that cocaine exposure, high environmental risk,
      male gender, and low child IQ each were related to poorer inhibitory control. An
      interaction indicated that cocaine effects were specific to children who lived in
      relatively low-risk environments. Cocaine-exposed children made an error sooner
      than unexposed children in low-risk environments but in the same trial as both
      exposed and unexposed children living in high-risk environments. Potential
      underlying mechanisms and the importance of examining cocaine exposure effects in
      the context of children's existing environment are discussed.

PMID- 14578696
TI  - Effects of gun admonitions on the behaviors and attitudes of school-aged boys.
AB  - Gun-safety programs frequently warn children not to touch guns with little
      consideration that the messages may enhance the allure of the guns. In the
      current study, boys rated and ranked their preference for a gun in comparison
      with other desirable objects. One week later, when left alone in the room with
      the objects, they were forbidden to touch either the gun or some other object.
      Observations of their behavior and reevaluation of their attitudes followed.
      Although the boys forbidden to touch the gun did not report an increased
      preference for it, all participants were significantly more likely to touch the
      forbidden gun than to touch other forbidden objects. Age, parent- and coach
      reported simulated gun-play, and coach-reported risky behavior predicted gun
      touching behavior. The results of the current study indicate that guns hold a
      unique allure and cast further doubt on the ability of gun admonitions to keep
      children safe around guns.

PMID- 14578697
TI  - Organic or psychosomatic? Facilitating inquiry with children and parents.

PMID- 14578698
TI  - Implications of attachment theory and research for developmental-behavioral
      pediatrics.
AB  - This article presents a basic overview of attachment theory, concepts, and
      research. The review includes a discussion of the nature of the attachment
      relationship, its origins in human evolutionary history, and common
      misconceptions about attachment. We describe phases in the development of
      attachment relationships and review research on factors that influence attachment
      variations. We discuss the implications of variations in early attachment
      relationships for later development (adaptation and maladaptation). And finally,
      we review briefly the implications of attachment theory and research for
      pediatric practice. Some key points are that (1) virtually all infants become
      attached to caregivers regardless of quality of care; (2) attachment
      relationships evolve in phases over time; (3) children with disabilities form
      attachment relationships in ways comparable to nondisabled children but manifest
      attachment somewhat differently; (4) the consequences for attachment of out-of
      home care, separations, and significant disruptions (e.g., adoption) depend on
      timing and circumstances; (5) many infant regulatory difficulties, as well as
      child behavior problems, originate in the caregiving relationship; and finally,
      (6) change in parent-child relationship disturbances is complex and requires time
      and effort.

PMID- 14578699
TI  - Problem of attention-deficit hyperactivity disorder treatment.

PMID- 14578700
TI  - Pigmented villonodular synovitis and giant cell tumor of the tendon sheath:
      scintigraphic findings in 10 cases.
AB  - The purpose of this report was to determine the pattern of thallium (T1-201)
      uptake in pigmented villonodular synovitis (PVNS) and giant cell tumor of the
      tendon sheath (GCTTS) and to evaluate for features that might help to distinguish
      these lesions from malignant disease. Scintigraphic images from patients
      subsequently found to have pigmented villonodular synovitis confirmed by
      histopathologic analysis were assessed. The patients had been evaluated with T1
      201 scintigraphy for a suspicious musculoskeletal lesion. All 6 patients with
      PVNS had significant T1-201 uptake on the early images with retention on the
      delayed images. The T1-201 activity was in a juxta-articular location and
      generally conformed to the synovial cavity with scattered irregular nodular
      components. Of 4 cases of giant cell tumor of the tendon sheath, all had T1-201
      uptake on the early images, and 3 cases (75%) also had uptake on the delayed
      images. T1-201 uptake is observed almost invariably in pigmented villonodular
      synovitis on both early and delayed images and can simulate the findings of
      malignant disease. Features that should raise suspicion of PVNS include close
      proximity to a joint, especially with distribution corresponding to that of the
      synovial cavity. When T1-201 activity is detected in a lesion in the hand or
      foot, giant cell tumor of the tendon sheath should be considered. Magnetic
      resonance imaging will often aid in the differentiation by demonstrating features
      of hemosiderin degradation products.

PMID- 14578701
TI  - Super scan leading to definitive diagnosis in a patient with recurrent syncope.
AB  - A "super scan" pattern detected on bone scintigraphy usually indicates either
      metabolic bone disease or diffuse metastases. We report a rare case of a 45-year
      old man with recurrent episodes of syncope of 10 years' duration in whom bone
      scintigraphy showed a super scan with an axial skeleton distribution of uptake.
      Bone marrow biopsy established the diagnosis of systemic mastocytosis. The few
      reports in the literature of super scans associated with systemic mastocytosis
      showed diffuse axial and appendicular increased uptake. The present case shows a
      super scan involving the axial skeleton, which led to the diagnosis of systemic
      mastocytosis.

PMID- 14578702
TI  - Increased myocardial uptake of iodine-123 metaiodobenzylguanidine on delayed
      images, compared with early images, in patients with multiple system atrophy.
AB  - We present 2 interesting cases of multiple system atrophy in which increased
      myocardial iodine-123 metaiodobenzylguanidine uptake was observed on delayed
      images (3 hours after injection) compared with early images (15 minutes after
      injection). These findings have not been previously described. The duration of
      symptoms was less than 1 year in both these patients. The mechanism responsible
      for these findings is not clearly understood, but could be related to the
      pathophysiological changes in the early stage of multiple systemic atrophy.

PMID- 14578703
TI  - Paraneoplastic encephalitis associated with cystic teratoma is detected by
      fluorodeoxyglucose positron emission tomography with negative magnetic resonance
      image findings.
AB  - The role of fluorodeoxyglucose (FDG) positron emission tomography (PET) as a
      functional imaging technique used in the evaluation of a variety of malignancies
      has been well known. Paraneoplastic encephalitis is a rare central nervous
      complication, which has been reported in some tumors. Traditionally, magnetic
      resonance imaging of the brain is performed to aid in its diagnosis. The authors
      report a case of paraneoplastic encephalitis, associated with cystic teratoma,
      which had positive FDG-PET findings but appeared normal on magnetic resonance
      imaging.

PMID- 14578704
TI  - Scintigraphic probability and angiographic diagnostic certainty in acute
      pulmonary embolism.
AB  - The objectives of this study were to determine if diagnostic certainty on
      angiography correlates with scintigraphic probability for the diagnosis of
      pulmonary embolism. From a total of 160 consecutive patients who underwent both
      nuclear imaging and invasive selective pulmonary angiography, we reviewed the
      xenon-133 ventilation images in 2 posterior oblique views and the Tc-99m
      macroaggregated serum albumin perfusion scans and angiograms of 40 patients (15
      men, 25 women; average age 57 years) who were discharged from the hospital on
      anticoagulants with a diagnosis of pulmonary embolism. The angiograms were
      reviewed and the diagnosis of embolism was considered certain in the presence of
      an intraluminal filling defect, a trailing embolus, or a branch occlusion equal
      to or larger than a segmental branch (n=29; 73%), and uncertain when the studies
      were reinterpreted as either equivocal or negative or in the presence of a
      single, small subsegmental filling defect of questionable clinical significance.
      The ventilation-perfusion scans were read as high (n=18; 45%), intermediate
      (n=10; 25%), or low (n=12; 30%) probability. The proportion of patients with
      diagnostic certainty on angiography in the high-, intermediate-, and low
      probability scintigraphic subgroups was, respectively, 100% (18 of 18), 70% (7 of
      10), and 33% (4 of 12) (P=0.004). In patients diagnosed with pulmonary embolism
      based on selective angiography, a lower probability of pulmonary embolism on
      ventilation-perfusion scintigraphy correlates with a lesser degree of diagnostic
      certainty on angiography and a higher incidence of single subsegmental emboli.

PMID- 14578705
TI  - Temporal correlation of the erythrocyte sedimentation rate with Tc-99m WBC uptake
      on children with inflammatory bowel diseases.
AB  - The goal of this study was to evaluate the temporal correlation of Tc-99m WBC
      studies with the erythrocyte sedimentation rate, a commonly used index of
      intensity of inflammation, in a large population of children with inflammatory
      bowel diseases. Over a 6-year period, 313 Tc-99m WBC studies were performed and
      the hospital charts of these consecutive children were reviewed. In each set of
      scans (0.5-1 hour and 2-3 hours) from the 313 patients, the bowel was divided
      into 8 segments resulting in 5008 bowel segments for scoring. The intensity of
      uptake on the planar images was graded on a scale of 0 to 6 and compared with the
      erythrocyte sedimentation rate obtained within 3 days, 1 week, 2 weeks, 1 month,
      3 months, 6 months, or 1 year of the Tc-99m WBC scan, when available. A dataset
      of 508 erythrocyte sedimentation rates was available for computation. In children
      with Crohn's disease, when erythrocyte sedimentation rate is obtained within 3
      days of the Tc-99m WBC scan, the correlation coefficient is R=0.314 (P<0.005),
      within 1 week R=0.358 (P<0.05), within 2 weeks R=0.254 (P=0.129), within 1 month
      R=-0.029 (P=0.84), within 3 months R=-0.002 (P=0.989), within 6 months R=0.241
      (P=0.145), and within 1 year R=0.068 (P=0.759). In children with Crohn's disease,
      the uptake of Tc-99m WBC correlates well with the erythrocyte sedimentation rate
      during the flare of inflammation, and the correlation progressively subsides
      after a few weeks. No such correlation was noted in children with ulcerative
      colitis.

PMID- 14578706
TI  - A moving Meckel's diverticulum on Tc-99m pertechnetate imaging in a patient with
      lower gastrointestinal bleeding.
AB  - Meckel's diverticulum is one of the most common causes of lower gastrointestinal
      hemorrhage in the young. We report a case of a 16-year-old youth who presented
      with a 3-day history of bright red bleeding per rectum. Clinical examination
      revealed pallor but nothing else of note. The patient had a hemoglobin of 9 G% on
      admission. Tc-99m pertechnetate scintigraphy was performed and demonstrated an
      abnormal focus in the pelvis on the right that changed in position during the
      course of imaging. A laparotomy was done and a 5 x 2-cm Meckel's diverticulum was
      removed from the ileum. Histopathologic examination revealed heterotopic gastric
      mucosa of the body type. The patient recovered fully after operation.

PMID- 14578707
TI  - Poor labeling of Tc-99m red blood cells in vivo in a radionuclide intestinal
      bleeding study of a patient who had recently undergone frequent blood
      transfusions.
AB  - The authors report poor labeling of Tc-99m red blood cells (RBCs) in vivo in a
      radionuclide intestinal bleeding study of a patient who had recently undergone
      frequent blood transfusions. The existence of RBC antibodies, as a result of the
      recent blood transfusions in this patient, was one of the causes of the poor
      labeling. In radionuclide bleeding studies with patients with recent blood
      transfusion, Tc-99m HSA-D must be chosen instead of Tc-99m RBCs in vivo.

PMID- 14578708
TI  - Chemotherapy-induced pericarditis on F-18 FDG positron emission tomography scan.
AB  - F-18 FDG positron emission tomography (PET) is a highly valuable imaging tool in
      evaluation and follow up of lymphoma and many other malignancies. Constrictive or
      effusive constrictive pericarditis is an uncommon complication of chemotherapy.
      The authors report a case in which pericardial FDG uptake was seen on a whole
      body PET scan performed for posttreatment follow-up evaluation for a mantle cell
      lymphoma.

PMID- 14578709
TI  - Spontaneous cervical spine cerebrospinal fluid leak with resultant intracranial
      hypotension.

PMID- 14578710
TI  - Renal cell carcinoma detected on Tc-99m-labeled red blood cell imaging.
AB  - A 61-year-old-man with persistent anemia was referred for a Tc-99m-labeled red
      blood cell (RBC) scan to detect any source of gastrointestinal bleeding. RBC
      scintigraphy revealed a hypervascular mass in the left renal fossa with
      functional loss in that kidney, suggesting the possibility of a renal cell
      carcinoma (RCC). Computed tomography confirmed this. Most RCC tumors are
      hypervascular on conventional angiography, with a maximum incidence in men in the
      sixth decade. The incidental diagnosis of RCC during radionuclide imaging has
      been documented in previous reports, but the authors are not aware of any case of
      RCC diagnosed during a RBC scan. This case illustrates the importance of careful
      attention to the appearance of the kidneys on radionuclide scans. Noticeable
      asymmetric renal activity in a patient without known renal parenchymal disease
      warrants further investigation.

PMID- 14578711
TI  - Scintigraphic findings in a case of bilateral urinomas and ascites secondary to
      posterior urethral valves.
AB  - The authors present the scintigraphic findings in a case of bilateral urinomas
      and ascites secondary to posterior urethral valves in a 9-day-old boy. There was
      progressive tracer accumulation in the urinomas and ascites with a distinct urine
      jet medially from the upper left kidney, which suggested direct urinary egress
      into the peritoneal cavity.

PMID- 14578712
TI  - Bone scan appearance in aggressive osteogenic sarcoma with pleural, lung, bone,
      and soft-tissue metastases.
AB  - A 40-year-old woman presented with a known case of osteogenic sarcoma of the
      right leg and underwent below-the-knee amputation. The preoperative workup was
      negative for distant metastases, and the patient was followed regularly. Two
      years later she developed dyspnea and chest pain. Computed tomography revealed
      diffuse left lung metastases with pleural involvement and nodular metastases in
      the right lung. Tc-99m methylene diphosphonate whole-body bone scanning revealed
      the amputated right leg with a clean stump but with widespread metastases in the
      right thigh involving soft tissue and bone, and the pelvis, left femur, and
      skull. In addition, diffuse left lung metastases involving both parietal pleura
      and lung parenchyma were seen. Tc-99m methylene diphosphonate uptake has been
      observed in the soft tissue and lungs in patients with osteogenic sarcoma but is
      rarely observed in practice with this degree of aggressiveness.

PMID- 14578713
TI  - "Cold" and "hot" osteomyelitis on bone scintigraphy.
AB  - Bone scanning is frequently used for the assessment of a child with pain around
      the hip joint. The authors present a child with septic hip arthritis in which a
      striking abnormality of complete absence of tracer uptake in an extensive region
      of the proximal femur was demonstrated on bone scintigraphy. Later during the
      course of his disease, markedly increased tracer uptake was seen along most of
      the femoral diaphysis with the exception of the avascular proximal bone. These
      scintigraphic findings represent extensive osteomyelitis of the femur with
      avascular necrosis of its proximal part.

PMID- 14578714
TI  - Unusual bilateral Tc-99m DPD uptake on bone scan.
AB  - A 74-year-old man with prostate cancer was screened for bone metastases. The scan
      exhibited severe degenerative skeletal changes (especially in the spine and the
      right knee) and catheter drainage of the bladder, but obviously no bone
      metastases. Surprisingly, 2 almost symmetric "devil-like"-looking lesions were
      noted in the frontolateral skull. The patient was treated with bilateral bore
      hole trepanation because of a subdural hematoma 3 weeks earlier. The lesions can
      be interpreted as augmented bone metabolism in these regions. Although subdural
      hematoma is fairly common (incidence, 15:100,000 annually), bilateral trepanation
      is only performed in approximately 5% of patients.

PMID- 14578715
TI  - Bilateral iliac metastases with sunburst pattern from prostate cancer.
AB  - Bone metastases from prostatic carcinoma commonly exhibit blastic characteristics
      with radiographically dense lesions. Occasionally they may demonstrate an unusual
      pattern of spiculation mimicking primary neoplasms of sarcomatous origin. The
      author presents a case of bone metastases from prostate carcinoma with bilateral
      and relatively symmetric iliac "sunburst" lesions documented on computed
      tomography and bone scintigraphy.

PMID- 14578716
TI  - Aneurysmal bone cyst of the sacrum: value of three-phase imaging.
AB  - Aneurysmal bone cyst is an uncommon nonneoplastic lesion that occurs
      predominantly during the first 2 decades of life. Angiographic- and tissue-phase
      imaging provided more striking evidence of this unexpected lesion than skeletal
      phase imaging in a 13-year-old girl with pain in the right buttock and posterior
      thigh.

PMID- 14578717
TI  - Scintigraphic findings of Mycobacterium avium complex tenosynovitis of the index
      finger in a patient with systemic lupus erythematosus.
AB  - The presented case is a 36-year-old woman with a history of systemic lupus
      erythematosus for 10 years. She had progressively painful swelling of the right
      index finger that later proved to be a rare case of tenosynovitis caused by
      Mycobacterium avium complex. Serial images of 3-phase bone scans, gallium scan,
      and magnetic resonance imaging demonstrate the area of involvement.

PMID- 14578718
TI  - Multifactorial uptake of Tc-99m methylene diphosphonate in chronic renal failure.
AB  - Soft-tissue calcifications are a frequent complication in patients with chronic
      renal failure. Numerous underlying factors are thought to favor their formation.
      A case is presented of a patient who was in end-stage renal failure, secondary to
      glomerulonephritis. A renal transplant had not been successful. She was on long
      term dialysis and had suffered aluminum toxicity (positive desferrioxamine test).
      She complained of proximal myopathy and bone pain.

PMID- 14578719
TI  - Confirmation by spiral CT of a partially occlusive thrombus of the right
      pulmonary artery suggested by a V/Q lung scan.
AB  - Findings on perfusion and ventilation imaging in a 24-year-old woman with
      anterior chest pain were consistent with pulmonary embolism involving the right
      lung. An astute physician raised the possibility of a thrombus occluding the
      right pulmonary artery, and subsequent spiral computed tomography confirmed the
      suspicion of an occluding thrombus at that site. Had spiral computed tomography
      been done first, the diagnosis would have been made much more rapidly.

PMID- 14578720
TI  - Respiratory artefact causing malpositioning of liver dome lesion in right lower
      lung.
AB  - The new combined positron emission (PET)/computed tomographic (CT) scanners have
      many advantages over PET scanners alone. However, physicians must be aware of the
      potential artefacts observed in PET/CT scanners. A body PET/CT was performed on
      an 81-year-old man with colorectal cancer. The CT-based, attenuation-corrected
      PET image showed a right lower lung lesion. However, there was no lung lesion on
      the transmission CT image. Nonattenuation-corrected PET, and rod source-based,
      attenuation-corrected PET images demonstrated focal uptake in the dome of the
      liver. Dedicated CT with intravenous contrast confirmed that the lesion was in
      the liver dome and not in the right lower lung. The liver lesion was misplaced to
      the right lower lung in the CT-based, attenuation-corrected PET image because of
      a respiratory artefact. To overcome this respiration artefact the authors suggest
      a routine review of the nonattenuation-corrected PET images, particularly when
      evaluating liver dome and lower lung lesions.

PMID- 14578721
TI  - Increased uptake on I-131 whole-body scintigraphy in Warthin tumor despite false
      negative Tc-99m pertechnetate salivary gland scintigraphy.
AB  - Whole-body I-131 scintigraphy is an important component of the postoperative
      follow-up of patients with well-differentiated thyroid cancer. However, false
      positive scans showing abnormal uptake in the absence of residual thyroid tissue
      or metastases may occur. Unless recognized as false positive, these abnormal
      sites of uptake may lead to unnecessary administration of therapeutic doses of I
      131. The authors report a patient with Warthin tumor whose I-131 whole-body scan
      demonstrated increased uptake in the parotid gland, despite a negative Tc-99m
      pertechnetate salivary gland scintigraphy.

PMID- 14578722
TI  - Parapharyngeal lymph node involvement in papillary thyroid carcinoma.
AB  - Papillary thyroid cancer extends to lymphatic nodes in approximately 40% of
      cases. Node involvement often occurs in the internal jugular and recurrent
      laryngeal chain on the side of the lesion. To the authors' knowledge, only 4
      cases with I-131 uptake in pharyngeal metastatic nodes have been reported
      previously in the literature. The authors report parapharyngeal node involvement
      demonstrated by I-131 scintigraphy in a patient with papillary thyroid cancer.

PMID- 14578723
TI  - Effects of intravenous fluid restriction on postoperative complications:
      comparison of two perioperative fluid regimens: a randomized assessor-blinded
      multicenter trial.
AB  - OBJECTIVE: To investigate the effect of a restricted intravenous fluid regimen
      versus a standard regimen on complications after colorectal resection. SUMMARY
      BACKGROUND DATA: Current fluid administration in major surgery causes a weight
      increase of 3-6 kg. Complications after colorectal surgery are reported in up to
      68% of patients. Associations between postoperative weight gain and poor survival
      as well as fluid overload and complications have been shown. METHODS: We did a
      randomized observer-blinded multicenter trial. After informed consent was
      obtained, 172 patients were allocated to either a restricted or a standard
      intraoperative and postoperative intravenous fluid regimen. The restricted
      regimen aimed at maintaining preoperative body weight; the standard regimen
      resembled everyday practice. The primary outcome measures were complications; the
      secondary measures were death and adverse effects. RESULTS: The restricted
      intravenous fluid regimen significantly reduced postoperative complications both
      by intention-to-treat (33% versus 51%, P = 0.013) and per-protocol (30% versus
      56%, P = 0.003) analyses. The numbers of both cardiopulmonary (7% versus 24%, P =
      0.007) and tissue-healing complications (16% versus 31%, P = 0.04) were
      significantly reduced. No patients died in the restricted group compared with 4
      deaths in the standard group (0% versus 4.7%, P = 0.12). No harmful adverse
      effects were observed. CONCLUSION: The restricted perioperative intravenous fluid
      regimen aiming at unchanged body weight reduces complications after elective
      colorectal resection.

PMID- 14578724
TI  - Evidence for conservative fluid administration following elective surgery.

PMID- 14578725
TI  - Preoperative dexamethasone improves surgical outcome after laparoscopic
      cholecystectomy: a randomized double-blind placebo-controlled trial.
AB  - OBJECTIVE: To determine the effects of preoperative dexamethasone on surgical
      outcome after laparoscopic cholecystectomy (LC). SUMMARY BACKGROUND DATA: Pain
      and fatigue are dominating symptoms after LC and may prolong convalescence.
      METHODS: In a double-blind, placebo-controlled study, 88 patients were randomized
      to intravenous dexamethasone (8 mg) or placebo 90 minutes before LC. Patients
      received a similar standardized anesthetic, surgical, and multimodal analgesic
      treatment. All patients were recommended 2 days postoperative duration of
      convalescence. The primary endpoints were fatigue and pain. Preoperatively and at
      several times during the first 24 postoperative hours, we measured C-reactive
      protein (CRP) and pulmonary function, pain scores, nausea, and number of vomiting
      episodes were registered. Analgesic and antiemetic requirements were recorded.
      Also, on a daily basis, patients reported scores of fatigue and pain before and
      during the first postoperative week and the dates for resumption of work and
      recreational activities. RESULTS: Eight patients were excluded from the study,
      leaving 40 patients in each study group for analysis. There were no apparent side
      effects of the study drug. Dexamethasone significantly reduced postoperative
      levels of CRP (P = 0.01), fatigue (P = 0.01), overall pain, and incisional pain
      during the first 24 postoperative hours (P < 0.05) and total requirements of
      opioids (P < 0.05). In addition, cumulated overall and visceral pain scores
      during the first postoperative week were significantly reduced (P < 0.05).
      Dexamethasone also reduced nausea and vomiting on the day of operation (P <
      0.05). Resumption of recreational activities was significantly faster in the
      dexamethasone group versus placebo group (median 1 day versus 2 days) (P < 0.05).
      CONCLUSION: Preoperative dexamethasone (8 mg) reduced pain, fatigue, nausea and
      vomiting, and duration of convalescence in patients undergoing noncomplicated LC,
      when compared with placebo, and is recommended for routine use.

PMID- 14578726
TI  - Preoperative steroids for laparoscopic surgery.

PMID- 14578728
TI  - Hand-assisted laparoscopic hepatectomy for solid tumor in the posterior portion
      of the right lobe: initial experience.
AB  - OBJECTIVE: To prove the feasibility of hand-assisted laparoscopic liver resection
      for tumors located in the posterior portion of the right hepatic lobe. SUMMARY
      BACKGROUND DATA: Use of laparoscopic liver resection remains limited due to
      problems with technique, especially when the tumor is located near the diaphragm,
      or in the posterior portion of the right lobe. METHODS: Between October 2001 and
      June 2002, a total of 7 patients with solid hepatic tumors involving the
      posterior portion of the right lobe of liver underwent hand-assisted laparoscopic
      hepatectomy with the HandPort system at our hospital. Surgical techniques used
      included CO2 pneumoperitoneum and the creation of a wound on the right upper
      quadrant of the abdomen for HandPort placement. The location of tumor and its
      transection margin were decided by laparoscopic ultrasound. The liver resection
      was performed using the Ultrashear without portal triad control, with the
      specimens obtained then placed in a bag and removed directly via the HandPort
      access. RESULTS: The 5 male and 2 female patients ranged in age from 41 to 76
      years (mean 62.3 +/- 14.4). Surgical procedures included partial hepatectomy for
      6 patients and segmentectomy for one, all successfully completed using a variant
      of the minimally invasive laparoscopic procedure without conversion to open
      surgery. The mean duration of the operation was 140.7 +/- 42.2 minutes (90-180).
      The blood loss during surgery was 257.1 +/- 159 mL (250-500), without any
      requirement for intraoperative or postoperative transfusion. Pathology revealed
      hemagioma (n = 2), colon cancer metastasis (n = 2), and hepatocellular carcinoma
      (n = 3). There were no deaths postoperatively, with 1 patient suffering bile
      leakage. Mean hospital stay was 5.3 +/- 1.3 days postsurgery. CONCLUSION: The
      results of this study suggest that laparoscopic liver resection using the
      HandPort system is feasible for selected patients with lesions in the posterior
      portion of the right hepatic lobe requiring limited resection. Individuals with
      small tumors may benefit; because a large abdominal incision is not required, the
      wound-related complication rate might be reduced.

PMID- 14578729
TI  - Laparoscopy-assisted distal gastrectomy for early gastric cancer: is it
      beneficial for patients of heavier weight?
AB  - OBJECTIVE: In this retrospective review, we evaluated the advantages and
      disadvantages of LADG for patients of heavier weight with early gastric cancer.
      SUMMARY BACKGROUND DATA: LADG has been used to treat early gastric cancer. We and
      others have reported less operative blood loss, less pain, early recovery of
      bowel activity, early restart of oral intake, and a shorter hospital stay with
      LADG compared with a conventional open method. There is, however, little
      information on the advantages of LADG for obese patients with early gastric
      cancer. METHODS: Between January 1996 and March 2002, 76 patients with
      preoperatively diagnosed early gastric carcinoma underwent LADG in our
      department. We classified these patients into 2 groups on the basis of body mass
      index (BMI). Nineteen patients had a high-BMI (>/= 24.2 kg/m2), and 57 patients
      had a normal-BMI (<24.2 kg/m2). We collected data by retrospectively reviewing
      the medical charts. RESULTS: Extension of the minilaparotomic incision or
      conversion to laparotomy was needed in 6 (32%) of the 19 patients in the high-BMI
      group, whereas only 3 (5%) of 57 patients in the normal-BMI group required
      either. In the high-BMI group, Roux-en-Y anastomosis rather than Billroth I
      anastomosis was adopted more often than in the normal-BMI group, due to the
      difficulty of the reconstruction (58% versus 4%, P = 0.001). Significantly longer
      operative time (370 +/- 61 minutes versus 317 +/- 58 minutes, P = 0.015) and
      prolonged recovery of bowel activity (3.5 +/- 1.0 days versus 2.6 +/- 1.0 days, P
      = 0.007) were observed in the patients in the high-BMI group. CONCLUSIONS: In the
      current study, LADG in patients of heavier weight was accompanied by more
      technical difficulties, and the disadvantages of longer operative time and
      delayed recovery of bowel activity was observed in patients of heavier weight.
      Heavier weight appears to be an ominous factor in the successful completion of
      LADG and should be considered in the decision to use LADG. There are still
      benefits of a decreased incidence of serious wound and hernia complications in
      successful cases.

PMID- 14578727
TI  - The role of epidural anesthesia and analgesia in surgical practice.
AB  - OBJECTIVE: To review the potential and proven benefits and complications of
      epidural anesthesia/analgesia. SUMMARY BACKGROUND DATA: Advances in
      analgesia/anesthesia have improved patient satisfaction and perioperative
      outcomes. Epidural anesthesia/analgesia is one of these advances that is gaining
      rapid acceptance due to a perceived reduction in morbidity and overall patient
      satisfaction. METHODS: A MEDLINE search was conducted for all pertinent articles
      on epidural anesthesia/analgesia. RESULTS: Retrospective, prospective, and meta
      analysis studies have demonstrated an improvement in surgical outcome through
      beneficial effects on perioperative pulmonary function, blunting the surgical
      stress response and improved analgesia. In particular, significant reduction in
      perioperative cardiac morbidity ( approximately 30%), pulmonary infections (
      approximately 40%), pulmonary embolism ( approximately 50%), ileus (
      approximately 2 days), acute renal failure ( approximately 30%), and blood loss (
      approximately 30%) were noted in our review of the literature. Potential
      complications related to epidural anesthesia/analgesia range from transient
      paresthesias (<10%) to potentially devastating epidural hematomas (0.0006%).
      CONCLUSIONS: Epidural anesthesia/analgesia has been demonstrated to improve
      postoperative outcome and attenuate the physiologic response to surgery.

PMID- 14578730
TI  - Gastroesophageal reflux: prevalence in adults older than 28 years after
      correction of esophageal atresia.
AB  - OBJECTIVE: To study the incidence of gastroesophageal reflux (GER)related
      complications after correction of esophageal atresia (EA). SUMMARY BACKGROUND
      DATA: The association of EA and GER in children is well known. However, little is
      known about the prevalence of GER and its potential complications in adults who
      have undergone correction of EA as a child. METHODS: Prospective analysis of the
      prevalence of GER and its complications over 28 years after correction of EA by
      means of a questionnaire, esophagogastroscopy, and histologic evaluation of
      esophageal biopsies. RESULTS: The questionnaire was returned by 38 (95%) of 40
      patients. A quarter of the patients had no complaints. Swallowing solid food was
      a problem for 13 patients (34%), and mashed foods for 2 (5%). Heartburn was
      experienced by 7 patients (18%), retrosternal pain by 8 (21%). However, none of
      the patients were using antireflux medication. Twenty-three patients (61%) agreed
      to undergo esophagogastroscopy, which showed macroscopic Barrett esophagus in 1
      patient, which was confirmed by histology. One patient developed complaints of
      dysphagia at the end of the study. A squamous cell esophageal carcinoma was
      diagnosed and treated by transthoracic subtotal esophagectomy. CONCLUSIONS: This
      study shows a high incidence of GER-related complications after correction of EA,
      but it is still very disputable if all EA patients should be screened at an adult
      age.

PMID- 14578731
TI  - The association of pretreatment health-related quality of life with surgical
      complications for patients undergoing open surgical resection for colorectal
      cancer.
AB  - OBJECTIVE: The purpose of this study was to define the association between
      pretreatment health-related quality of life (HRQL) and surgical complications for
      patients with colorectal cancer. SUMMARY BACKGROUND DATA: For patients with
      colorectal cancer, surgical complications arise from an interaction between
      underlying medical comorbidity, colorectal cancer severity, and quality and type
      of treatment provided. Measurement of HRQL provides a summarization of well-being
      in the context of medical comorbidity and colorectal cancer severity. The
      summarization of these factors may be useful in prospective risk assessment of
      patients about to undergo surgery for colorectal cancer. METHODS: A single
      institution, prospective, cohort study of patients with colorectal adenocarcinoma
      was performed from August 1, 1999, to March 31, 2002. Before treatment, all
      participants completed Medical Outcomes Survey SF-36 (SF-36); after the first
      year of the study, patients also completed the colorectal cancer module of the
      Functional Assessment of Cancer Therapy survey (FACT-C). Information was
      collected on demographics, treatment, tumor variables, and complications.
      RESULTS: Ninety-seven patients have undergone open resection of their colorectal
      cancer. All patients completed SF-36; 65 completed FACT-C. Thirty patients (31%)
      experienced complications, including 4 (4%) deaths. Age, race, albumin level,
      American Society of Anesthesia class, specialty surgical training, tumor
      location, and stage were not associated with complications in univariate
      analysis. Patients experiencing surgical complications had significantly lower
      HRQL scores on SF-36 Social Functioning, General Health Perception, and Mental
      Health Index scales as well as the Mental Health Component summary score. FACT-C
      Social/Family, Emotional, Functional Well-Being scores, and the Colorectal Cancer
      Concerns score were also significantly lower for patients sustaining
      complications. When these HRQL scales were examined in a multivariate model
      including albumin level, tumor location, and ASA class, SF-36 Social Functioning
      (Odds Ratio [OR] = 0.98; 95% Confidence Interval [CI] = 0.97-0.99) and FACT-C
      Colorectal Cancer Concerns (OR = 0.89; 95% CI = 0.79-0.99) scales retained a
      significant association with complications. CONCLUSIONS: Pretreatment HRQL scores
      as measured by several scales of SF-36 and FACT-C were significantly associated
      with complications. Future studies should concentrate on defining the predictive
      role of HRQL in determining surgical outcome for patients with colorectal cancer.

PMID- 14578732
TI  - Gallstone formation prophylaxis after gastric restrictive procedures for weight
      loss: a randomized double-blind placebo-controlled trial.
AB  - OBJECT: To determine if a 6-month regimen of prophylactic ursodeoxycholic acid is
      effective in the prevention of gallstones. SUMMARY BACKGROUND DATA: Rapid weight
      loss after surgery for the treatment of morbid obesity is associated with a high
      incidence of gallstone formation. METHODS: Patients with vertical banded
      gastroplasty (VBG) and adjustable gastric banding (AGB) were enrolled in this
      study. A single-center, randomized, double-blind, prospective trial evaluated 500
      mg of ursodeoxycholic acid versus placebo, beginning within 3 days after surgery
      and continuing for 6 months or until gallstone development, for patients with
      morbid obesity. Transabdominal sonography or abdominal CT scan was obtained
      preoperatively at 3, 6, 12, and 24 months after surgery or until gallstone
      formation. RESULTS: From March 1997 to April 2000, 262 patients were submitted to
      surgery. Seventy-seven patients refused to participate in the study; 43 patients
      with previous gallstone operation or verified gallstones preoperatively were
      excluded. Of 152 patients, 76 were randomized to placebo and 76 to 500 mg of
      ursodeoxycholic acid daily. Preoperative age, sex, weight, BMI, and postoperative
      weight loss were not significantly different between groups. Gallstone formation
      was significantly less (P = 0.0018, Fisher exact test) frequent with
      ursodeoxycholic acid than with placebo at 12 months, 3% versus 22%, and 8% versus
      30% (P = 0.0022) at 24 months, cholecystectomy in 4.7% versus 12%, respectively
      (P < 0,02, Fisher exact test). CONCLUSION: A daily dose of 500 mg of
      ursodeoxycholic acid for 6 months is effective prophylaxis for gallstone
      formation following gastric restrictive procedures.

PMID- 14578733
TI  - Selection criteria for repeat hepatectomy in patients with recurrent
      hepatocellular carcinoma.
AB  - OBJECTIVE: The purpose of this study was to evaluate prognostic factors in
      patients with recurrence after curative resection of hepatocellular carcinoma
      (HCC) and to identify selection criteria for repeat resection. SUMMARY BACKGROUND
      DATA: Recent studies have demonstrated that repeat hepatectomy is effective for
      treating intrahepatic recurrent HCC in selected patients. However, the prognostic
      factors in these patients have not been fully evaluated. METHODS: From October
      1994 to December 2000, 334 patients underwent primary resection for HCC, and 67
      received a 2nd hepatectomy for recurrent HCC. The survival results in these 67
      patients were analyzed, and prognostic factors were determined using 38
      clinicopathological variables. The prognosis and operative risk in 11 and 6
      patients who received a 3rd and 4th resection were also evaluated. RESULTS: The
      overall 1-, 3-, and 5-year survival rates of the 334 patients after primary
      hepatectomy were 94%, 75%, and 56%, while those of the 67 patients after a 2nd
      resection were 93%, 70%, and 56%, respectively. There was no difference in
      survival (P = 0.64). All of the patients who underwent a 3rd or 4th are currently
      alive at a median follow-up of 2.5 and 1.4 years, respectively. The operative
      time and blood loss in the 2nd resection in patients who underwent a major
      primary resection were not different from those in patients who underwent minor
      hepatectomy at the 1st resection, and there were also no differences in these
      variables among the 2nd, 3rd, and 4th resections. In a multivariate analysis,
      absence of portal invasion at the 2nd resection (P = 0.01), single HCC at primary
      hepatectomy (P = 0.01), and a disease-free interval of 1 year or more after
      primary hepatectomy (P = 0.02) were independent prognostic factors after the 2nd
      resection. Twenty-nine patients with all 3 of these factors showed 3- and 5-year
      survival rates of 100% and 86%, respectively, after the 2nd resection.
      CONCLUSIONS: Repeat hepatic resection is the treatment of choice for patients who
      have previously undergone resection of a single HCC at the primary resection and
      in whom recurrence developed after a disease-free interval of 1 year or more and
      the recurrent tumor had no portal invasion.

PMID- 14578734
TI  - Comparison of clinicopathologic characteristics and outcomes after resection in
      patients with hepatocellular carcinoma treated in the United States, France, and
      Japan.
AB  - OBJECTIVE: To compare the clinicopathologic characteristics and outcomes after
      resection of patients with hepatocellular carcinoma (HCC) treated in the United
      States, France, and Japan. SUMMARY BACKGROUND DATA: Some epidemiologic data
      suggests that HCC in different regions of the world may represent different forms
      of the disease. METHODS: We compared the patient and tumor characteristics,
      underlying liver damage, and surgical outcomes of 586 patients who underwent
      resection of HCC from a multi-institutional database. RESULTS: A total of 169
      patients were treated in the United States, 187 in France, and 230 in Japan. The
      median tumor size for patients treated in the United States was 8 cm, compared
      with 6 cm and 3.5 cm in France and Japan, respectively (P < 0.001); 20%, 38%, and
      74% of patients in the United States, France, and Japan, respectively, had
      positive hepatitis C serology (P < 0.001). In addition, 65% of patients in Japan
      had severe fibrosis/cirrhosis in the adjacent liver compared with 52% and 23% of
      patients in France and the United States, respectively (P < 0.001). There was no
      association between site of treatment and 30-day (P = 0.4) or 1-year mortality (P
      = 0.3). The 5-year survival of patients treated in United States, France, and
      Japan was not statistically different (31% vs. 31% vs. 41%, respectively; P =
      0.3). CONCLUSIONS: Although the etiology of HCC and clinicopathologic
      characteristics of patients treated at western and eastern centers vary widely,
      postresection 5-year survival is similar when controlling for these factors.
      Future studies should account for histopathologic differences using uniform
      criteria to allow better comparison of results.

PMID- 14578735
TI  - Hepatectomy with portal vein resection for hilar cholangiocarcinoma: audit of 52
      consecutive cases.
AB  - OBJECTIVE: To better determine the role of portal vein resection and its effect
      on survival, as well as to appreciate the impact of portal vein invasion on
      prognosis in hilar cholangiocarcinoma. SUMMARY BACKGROUND DATA: Hepatectomy with
      portal vein resection is sometimes performed for locally advanced hilar
      cholangiocarcinoma. However, the significance of microscopic invasion of the
      portal vein has not been determined. METHODS: Medical records of 160 patients
      with hilar cholangiocarcinoma who underwent macroscopically curative hepatectomy
      with (n = 52) or without portal vein resection (n = 108) were reviewed. Invasion
      of the portal vein was assessed histologically on the surgical specimen, and
      results were correlated with clinicopathologic features and survival. RESULTS:
      Surgical mortality, including all hospital deaths, was similar in patients who
      did and did not undergo portal vein resection (9.6% vs. 9.3%), but the primary
      tumor was more advanced in patients who underwent portal vein resection.
      Histologically, no invasion was found in 16 (30.8%) of resected portal veins.
      However, dense fibrosis adjacent to the portal vein was common, and the mean
      distance between the leading edge of cancer cells and the adventitia of the
      portal vein was 437 +/- 431 mum. The prognosis was worse in patients with than
      without portal vein resection (5-year survival, 9.9% vs. 36.8%; P < 0.0001). The
      presence or absence of microscopic invasion of the resected portal vein did not
      influence survival (16.6 months in patients with microscopic invasion vs. 19.4
      months in those without; P = 0.1506). Multivariate analysis identified histologic
      differentiation, lymph node metastasis, and macroscopic portal vein invasion as
      independent prognostic factors. CONCLUSIONS: Microscopic invasion of the portal
      vein may be misdiagnosed clinically in patients with hilar cholangiocarcinoma.
      However, the distance between tumor and adventitia is so narrow that curative
      resection without portal vein resection is unlikely to be possible. Gross portal
      vein invasion has a negative impact on survival, and hepatectomy with portal vein
      resection can offer long-term survival in some patients with advanced hilar
      cholangiocarcinoma.

PMID- 14578736
TI  - BREASTAID: Clinical results from early development of a clinical decision rule
      for palpable solid breast masses.
AB  - OBJECTIVE: To develop a clinical decision rule (entitled BREASTAID) that will
      predict the probability of malignancy in women with palpable solid breast masses.
      SUMMARY BACKGROUND DATA: Currently, 80% of open breast biopsies are benign,
      resulting in excessive economic, psychologic, and physical morbidity. METHODS: A
      total of 452 solid breast masses were evaluated in a surgical breast clinic
      between November 1994 and February 1998. Breast cancer status was defined
      histologically as ductal carcinoma in situ or invasive cancer. Noncancer status
      included benign histology, mass resolution, or stability at 12-month follow-up.
      Data were collected on risk factors, clinical breast examination, mammography,
      and cytology results. Three multiple logistic regression models were used to
      generate the probability of cancer at 3 logical steps in the workup; Bayes'
      theorem was applied in a stepwise fashion to generate a final probability of
      cancer. RESULTS: A model incorporating only clinical breast examination and
      mammography resulted in an excessive number of either missed cases or biopsies
      compared with one that included cytology. Using a cut-point of 4%, this latter
      BREASTAID model had 97.6% sensitivity and 85.1% specificity. Compared with triple
      diagnosis, BREASTAID would have reduced the open biopsy rate from 39.8% (180 of
      452) to 22.3% (101 of 452), improving the diagnostic yield from 22.7% to 40.6%.
      CONCLUSIONS: This study convincingly demonstrates that at minimum, clinical,
      radiologic, and cytologic evaluations are required to accurately evaluate a solid
      breast mass. BREASTAID has the potential to minimize the number of open biopsies
      performed while allowing safe triage to follow-up. Before widespread application,
      further validation studies are required.

PMID- 14578737
TI  - Intraoperative ultrasonographically guided excisional biopsy or vacuum-assisted
      core needle biopsy for nonpalpable breast lesions.
AB  - OBJECTIVE: To compare duration and rates of underestimation and complete excision
      for nonpalpable breast lesions using either intraoperative ultrasonographically
      guided excisioned biopsy (IUGE) or directional vacuum-assisted biopsy (DVAB).
      SUMMARY BACKGROUND DATA: Percutaneous ultrasonography-guided core needle biopsy
      is preferable to stereotactic biopsy for treatment of nonpalpable breast lesions;
      however, underestimation and false-negative results can occur, and rebiopsy may
      be required. To date, however, there has been no comparison of these two
      procedures in terms of diagnostic accuracy and duration. METHODS: For 4
      consecutive years, IUGE was performed for 104 nonpalpable breast lesions and DVAB
      for 128 lesions at Chang Gung Memorial Hospital. Of the DVAB cases, the handheld
      mammotome was used for 53 procedures, with all lesions removed as completely as
      possible. The duration of the two procedures was calculated from initial skin
      incision until completion of wound closure. Most of the patients with benign
      pathology underwent ultrasonographic examination at 3 months after surgery, with
      a follow-up examination at 1 year. Surgery was performed subsequently for all of
      the malignancy cases. RESULTS: The average ages and mean tumor sizes for patients
      undergoing IUGE or DVAB were 46 and 47 years and 1.1 and 1.0 cm, respectively.
      The average IUGE and DVAB surgery durations for 88 benign tumors and 117 benign
      lesions were 44.3 and 21.5 minutes, respectively (P < 0.001), and 43.5 and 20.6
      minutes for the malignant tumors (n = 16 and n = 11), respectively (P = 0.036).
      The IUGE and DVAB surgery durations for tumors <1 cm in diameter were 43.5 and
      20.6 minutes, respectively, and 44.2 and 23.6 minutes for tumors over that size
      (P < 0.001). An older-model mammotome was used for 75 patients, with an average
      duration of 24 minutes in comparison to 18 minutes for the handheld variant (P <
      0.001). No false-negative results were noted and, except in the case of the
      malignant tumors, there was no need for reexcisional biopsy. Further, there were
      no underestimates of the disease for the 4 cases of atypical ductal hyperplasia
      and the 12 of noninvasive carcinoma. No further ultrasonographic evidence of
      tumors was noted for 95% of the benign pathologies, with no residual abnormality
      detected for 13 of the 27 malignant tumors after IUGE or DVAB. CONCLUSIONS: For
      treatment of nonpalpable breast lesions, both IUGE and DVAB eliminate false
      negative results, underestimates, and the requirement for reexcisional biopsies.
      In comparison to IUGE, DVAB is more convenient and time efficient for excisional
      biopsy of nonpalpable breast lesions.

PMID- 14578738
TI  - Is sentinel lymph node mapping indicated for isolated local and in-transit
      recurrent melanoma?
AB  - OBJECTIVE: To determine the feasibility of sentinel lymph node mapping in local
      and in-transit recurrent melanoma. SUMMARY BACKGROUND DATA: The accuracy of
      intraoperative lymphatic mapping and sentinel lymphadenectomy (LM/SL) for
      identification of occult lymph node metastases is well established in primary
      melanoma. We hypothesized that LM/SL could be useful to detect regional node
      metastases in patients with isolated local and in-transit recurrent melanoma
      (RM). METHODS: Review of our prospective melanoma database of 1600 LM/SL patients
      identified 30 patients who underwent LM/SL for RM. Patients with tumor-positive
      sentinel nodes (SNs) were considered for completion lymph node dissection.
      RESULTS: Of the 30 patients, 17 were men and 13 were women; their median age was
      57 years (range, 29-86 years). Primary lesions were more often on the extremities
      (40%) than the head and neck (33%) or the trunk (8%). At least 1 SN was
      identified in each lymph node basin that drained an RM. Of the 14 (47%) patients
      with tumor-positive SNs, 11 (78%) underwent complete lymph node dissection; 4 had
      tumor-positive non-SNs. The median disease-free survival after LM/SL was 16
      months (range, 1-108 months) when an SN was positive and 36 months (range, 6-132
      months) when SNs were negative. At a median follow-up of 20 months (range, 2-48
      months), there were no dissected basin recurrences after a tumor-negative SNs.
      CONCLUSIONS: LM/SL can accurately identify SNs draining an RM, and the high rate
      of SN metastases and associated poor disease-free survival for patients with
      tumor-positive SN suggests that LM/SL should be routinely considered in the
      management of patients with isolated RM.

PMID- 14578739
TI  - Bone marrow failure following severe injury in humans.
AB  - BACKGROUND: Hematopoietic failure has been observed in experimental animals
      following shock and injury. In humans, bone marrow dysfunction has been observed
      in the red cell component and characterized by a persistent anemia, low
      reticulocyte counts, and the need for repeated transfusions despite adequate iron
      stores. While a quantitative defect in white blood cell count has not been noted,
      an alteration in white blood cell function manifesting as an increased
      susceptibility to infection is well established. Since the etiology of this
      anemia remains unknown and the bone marrow has been rarely studied following
      injury, we measured various parameters of hematopoiesis directly using bone
      marrow from trauma patients and tested the hypothesis that trauma results in
      profound bone marrow dysfunction, which could explain both the persistent anemia
      and the alteration in white blood cell function. METHODS: Bone marrow aspirates
      and peripheral blood were obtained between day 1 and 7 following injury from 45
      multiple trauma patients. Normal volunteers served as controls. Peripheral blood
      was assayed for hemoglobin concentration, reticulocyte count, erythropoietin
      levels, white blood cell count, and differential. Peripheral blood and bone
      marrow were cultured for hematopoietic progenitors (CFU-GM, BFU-E, and CFU-E
      colonies). RESULTS: Bone marrow CFU-GM, BFU-E, and CFU-E colony formation was
      significantly reduced while peripheral blood CFU-GM, BFU-E, and CFU-E was
      increased in the trauma patients compared with normal volunteers. Bone marrow
      stroma failed to grow to confluence by day 14 in >90% of trauma patients. In
      contrast, bone marrow stroma from volunteers always reached confluence between
      days 10 and 14 in culture. The mean hemoglobin concentration and reticulocyte
      counts of the trauma patients were 8.6 +/- 1.0 g/dL and 2.75 +/- 0.7%
      respectively, while their plasma erythropoietin levels were 2 to 10 times greater
      than control values. CONCLUSIONS: Release of immature white blood cells into the
      circulation may also contribute to a failure to clear infection and an increased
      propensity to organ failure. Concomitantly, profound changes occur within the
      bone marrow, which include the increased release of erythroid and myeloid
      progenitors into the circulation, a decrease in progenitor cell growth within the
      bone marrow, and an impaired growth of the bone marrow stroma. Erythropoietin
      levels are preserved following trauma, implying that the persistent anemia of
      injury is related to the failure of the bone marrow to respond to erythropoietin.

PMID- 14578740
TI  - Pseudomonas aeruginosa expresses a lethal virulence determinant, the PA-I
      lectin/adhesin, in the intestinal tract of a stressed host: the role of epithelia
      cell contact and molecules of the Quorum Sensing Signaling System.
AB  - OBJECTIVE: We have previously demonstrated that P. aeruginosa can have profound
      effects on the intestinal epithelial barrier via one of its virulence factors,
      the PA-I lectin/adhesin. The aims of the present study were to further
      characterize the interaction of P. aeruginosa and the intestinal epithelium using
      both in vitro and in vivo approaches. METHODS: In vitro assays examining the
      effect of bacterial growth phase, epithelial cell contact, and butanoyl
      homoserine lactone (C4-HSL), a quorum sensing signaling molecule know to affect
      various extracellular virulence factors in P. aeruginosa, on PA-I expression in
      P. aeruginosa were performed. In vivo studies were carried out by modeling
      catabolic stress in mice using a 30% surgical hepatectomy and direct introduction
      of P. aeruginosa and various virulence components into the cecum. The effect of
      this model on PA-I expression in P. aeruginosa was determined. RESULTS: Results
      demonstrated that PA-I expression in P. aeruginosa is affected by its phase of
      growth, its contact to the intestinal epithelium, and its exposure to the quorum
      sensing molecule, C4-HSL. Furthermore, data from the present study suggest that
      the PA-I lectin/adhesin of P. aeruginosa may be increased in vivo by local
      factors within the cecum of mice in response to surgical stress. CONCLUSIONS:
      These data indicate that multiple factors present in the intestinal
      microenvironment of a stressed host may induce certain opportunistic pathogens to
      express key virulence factors leading to a state of lethal gut-derived sepsis.

PMID- 14578741
TI  - Systemic intravenous infusion of bovine hemoglobin significantly reduces
      microcirculatory dysfunction in experimentally induced pancreatitis in the rat.
AB  - OBJECTIVE: To evaluate the effectiveness of bovine hemoglobin on pancreatic
      microcirculation and outcome in experimental acute rodent pancreatitis. SUMMARY
      BACKGROUND DATA: Stasis of the pancreatic microcirculation initiates and
      aggravates acute pancreatitis. Hydroxyethyl-starch (HES) has been shown to
      improve pancreatic microcirculation. Similarly, bovine hemoglobin might improve
      rheology due to its colloid effect, but additionally supplies oxygen to oxygen
      depleted pancreatic tissue. METHODS: In Wistar rats, severe acute pancreatitis
      was induced by administration of glucodeoxycholic acid i.d. and cerulein i.v.
      Pancreatic microcirculation was continuously monitored by fluorescence
      microscopy. Fifteen minutes after the initiation of acute pancreatitis, animals
      received either 0.8 mL bovine hemoglobin (Oxyglobin), HES, or 2.4 mL 0.9% NaCl
      i.v. at random. After 6 hours, animals were killed and histopathological damage
      of the pancreas was assessed using a validated histology score (0-16). RESULTS:
      In comparison to controls, pancreatic microcirculation improved significantly in
      the HBOC group (mean difference of capillary density 31.4%; standard error 5.6%;
      P < 0.001; 95% confidence interval for difference 17.5-45.3). HES was not as
      effective as HBOC substitution. The histology score revealed less tissue damage
      in the HBOC group [6.25 vs. 9.25 (3-8.5 vs. 8-10.75, P < 0.001)] in comparison to
      controls and also in comparison to the HES group [6.25 vs. 8 (3-8.5 vs. 6.5
      10.25, P < 0.006)]. CONCLUSIONS: In severe acute pancreatitis, single i.v.
      injection of bovine hemoglobin improves pancreatic microcirculation and reduces
      tissue damage.

PMID- 14578742
TI  - Anthony Eden's (Lord Avon) biliary tract saga.
AB  - Anthony Eden (Lord Avon) was the youngest foreign secretary in Great Britain's
      history. He subsequently became Prime Minister, succeeding Winston Churchill.
      Eden had the misfortune to have, during cholecystectomy, a biliary tract injury
      which required four subsequent biliary tract operations. He was subject to
      recurrent fevers and postoperative disability at important times in his career
      and during international crises. This report details the operative procedures
      used and his clinical status at crucial times in national and international
      affairs.

PMID- 14578743
TI  - Induction of heme oxygenase-1 in kidneys during ex vivo warm perfusion.
AB  - BACKGROUND: Reperfusion injury plays a pivotal role in the occurrence of delayed
      graft function and chronic rejection. Heme oxygenase-1 (HO-1), an inducible heat
      shock protein, is known to have cytoprotective effects against reperfusion
      injury. We report on the potential for ex vivo induction of HO-1 expression
      during acellular warm perfusion of canine kidneys, using cobalt protoporphyrin
      (CoPP) as an HO-1 inducer and zinc protoporphyrin as an HO-1 inhibitor. METHODS:
      Canine kidneys were used to evaluate HO-1 increase after exposure to warm
      ischemia (WI), hypothermic perfusion (mechanical perfusion [MP], 4 degrees C),
      warm perfusion (exsanguineous metabolic support [EMS], 32 degrees C), or various
      combinations. RESULTS: WI alone, MP, or EMS with or without WI, had no effect on
      HO-1 activity. However, the presence of CoPP during EMS perfusion resulted in a
      significant increase in kidney HO-1 activity, whereas zinc protoporphyrin reduced
      HO-1 activity. The presence of CoPP during MP did not induce elevated HO-1
      expression. The results of our study demonstrate that sufficient metabolism
      supporting new protein synthesis resulting in the expression of the protective
      gene, HO-1, can be accomplished during an acellular near-normothermic perfusion
      using CoPP. Most importantly, the time required for ex vivo HO-1 induction with
      this method is compatible with the current time frame for which organs are
      preserved clinically. CONCLUSIONS: The ability to induce HO-1 expression ex vivo
      eliminates the need for donor therapy to induce HO-1 increase before retrieving
      organs and also prevents the potential of decreasing HO-1 enzyme activity that is
      known to occur with temperature-mediated inhibition of oxidative metabolism
      during hypothermic organ storage.

PMID- 14578744
TI  - Brain death induces apoptosis in donor liver of the rat.
AB  - BACKGROUND: A difference in short- and long-term function between living-related
      and cadaveric donor organs is consistently shown in kidney- and liver-transplant
      studies. We hypothesize that this is caused by induction of apoptosis and
      inflammation of the potential graft because of the phase of brain death (BD) in
      the cadaveric donor that predisposes for additional transplant injury.
      Previously, we have shown inflammation in the liver of brain-dead donors by
      increased expression of cell adhesion molecules and influx of leukocytes. The key
      inflammatory mediator in inflammation is tumor necrosis factor (TNF)-alpha. In
      addition to being involved in inflammation, TNF-alpha also activates the
      potential detrimental process of apoptosis and, on the other hand, activates an
      antiapoptotic survival pathway by way of NF-kB. The aim of the present study was
      to investigate whether the inflammatory response in the liver of brain-dead
      donors is accompanied by changes in apoptosis and in expression of apoptosis
      related proteins, in particular those regulated by NF-kB. METHODS: BD was induced
      by inflation of an intracranially placed balloon. Apoptosis was assessed by
      caspase-3 enzyme activity and terminal deoxynucleotide transferase-mediated dUTP
      nick-end labeling (TUNEL) assay. Changes in expression of proteins involved in
      pathways leading to apoptosis were studied by determination of mRNA levels using
      semiquantitative reverse-transcriptase polymerase chain reaction followed by
      image analysis. TNF-receptor (TNFR), Fas, and Fas-ligand (FasL) were used as
      indicators for activation of the death receptor mediated pathway. Bcl-2, Bax,
      Bak, Bid, and A1 were used as indicators for activation of the mitochondrial
      pathway. RESULTS: After 6 hours of normotensive BD, the number of apoptotic cells
      and caspase-3 activity were significantly increased compared with non-brain-dead
      control rats. TUNEL staining revealed that the apoptotic cells were primarily
      hepatocytes. mRNA levels of all NF-kappaB induced activators (Fas, bid) and
      inhibitors (A1, BCl-xl, cIAP2) of both apoptotic pathways were significantly
      increased in liver tissue of BD donors versus non-BD controls. CONCLUSIONS: The
      phase of BD in the donor induces increased apoptosis of hepatocytes despite an
      enhanced expression of NF-kB-dependent antiapoptotic genes.

PMID- 14578745
TI  - FTY720 does not abrogate acute graft-versus-host disease in the dog leukocyte
      antigen-nonidentical unrelated canine model.
AB  - BACKGROUND: Acute graft-versus-host disease (GVHD) remains a significant
      impediment to successful hematopoietic stem-cell transplantation (HSCT). Here, we
      examined the effectiveness of 2-amino-2-(2-[4-octylphenyl]ethyl)-1,3-propanediol
      hydrochloride (FTY720), an immunosuppressant that retraffics activated
      lymphocytes to secondary lymphoid organs, for the treatment of acute GVHD in an
      established dog leukocyte antigen-nonidentical unrelated canine HSCT model.
      METHODS: Dogs were given HSCT after conditioning with 920 cGy total body
      irradiation. The dogs received methotrexate 0.4 mg/kg/day on days 1, 3, 6, and 11
      and FTY720 (5 mg/kg/day orally) after developing GVHD. RESULTS: Five of six dogs
      achieved engraftment, developed acute GVHD, and were treated with FTY720. FTY720
      resulted in a profound decrease in lymphocytes and a temporary mitigation of
      clinical GVHD; however, GVHD recurred in all dogs. Four of five dogs were
      euthanized because of severe GVHD and the fifth because of severe inanition
      associated with moderate GVHD. CONCLUSIONS: Compared with controls, treatment of
      GVHD with FTY720 did not control this complication or significantly increase
      survival.

PMID- 14578746
TI  - A short course of mycophenolate immunosuppression inhibits rejection, but not
      tolerance, of rat liver allografts in association with inhibition of interleukin
      4 and alloantibody responses.
AB  - BACKGROUND: Some immunosuppressive drug therapies inhibit transplant tolerance in
      animal models, and we have shown that treatment of recipients with
      methylprednisolone, but not cyclosporine, inhibits spontaneous acceptance of
      liver transplants. This study investigates the effects of mycophenolate mofetil
      (MMF) on liver acceptance and rejection. METHODS: Piebald Virol Glaxo rat livers
      were transplanted into Dark Agouti recipients, which spontaneously tolerate (TOL)
      the liver, or into Lewis recipients, which reject (REJ) the liver. MMF (40
      mg/kg/day subcutaneously) was given for 5 days from days 0 to 4 (early) or from
      days 3 to 7 (late). In separate experiments, liver grafts were collected for
      assessment of infiltrate and of interleukin (IL)-2, IL-4, IL-10, and interferon
      gamma mRNA expression. RESULTS: TOL liver transplants had a median survival time
      (MST) of more than 100 days (n=6), and neither early nor late MMF treatment of
      TOL transplants reduced survival (MST 85 days, P=0.19 and 78 days, P=0.08,
      respectively). Liver failure in most of these animals was the result of biliary
      problems, not rejection. There were few consistent differences between treated
      and untreated TOL animals in infiltrate or liver cytokine expression, although
      there was a moderate reduction in T-cell infiltrate in MMF-treated TOL animals
      (P=0.003 on day 5 TOL). In contrast, REJ transplants had an MST of 13 days
      (n=10), and early MMF treatment led to five of six animals surviving more than
      100 days (P=0.0002), whereas late treatment was much less effective, with one of
      six animals surviving more than 100 days. REJ livers had significantly more IL-4
      mRNA expression and immunoglobulin G1 deposition in the graft than TOL livers,
      and this was inhibited by early, but not late, MMF treatment. CONCLUSIONS: MMF
      treatment inhibited rejection but not acceptance of liver allografts. Early
      administration was more effective in preventing rejection and demonstrated a more
      marked effect on IL-4 expression and alloantibody deposition than on graft T-cell
      infiltrate and expression of other cytokines.

PMID- 14578747
TI  - Differential effect of cyclosporine A and SDZ RAD on neointima formation of
      carotid allografts in apolipoprotein E-deficient mice.
AB  - BACKGROUND: Apolipoprotein E-deficient (apoE-/-) mice spontaneously develop
      hypercholesterolemia and atherosclerotic lesions. This may be an appropriate
      background for the development of graft vessel disease. The authors therefore
      investigated the effects of cyclosporine A (CsA) and SDZ RAD (RAD, everolimus,
      Certican) on neointima formation of carotid allografts in apoE-/- mice. To
      ascertain that equipotent immunosuppressive doses were used, the authors also
      investigated their effects on cardiac allografts using the same wild-type strain
      combination. METHODS: Heterotopic heart allotransplantation was performed in the
      BALB/c to C57BL/6 strain combination. Graft survival was monitored daily.
      Orthotopic carotid artery allotransplantation was performed from BALB/c to apoE-/
      (C57BL/6) mice. Groups of mice were treated for 8 weeks with placebo; CsA 10,
      20, and 30 mg/kg/d; or RAD 0.3, 1.0, and 3.0 mg/kg/d using ALZET minipumps. Body
      weight, CsA blood levels, serum lipids, and histology were examined 8 weeks after
      transplantation or on the day of rejection. RESULTS: Compared with the placebo
      group, CsA or RAD did not affect body weight. Both CsA and RAD prolonged the
      survival of cardiac grafts in a dose-dependent manner. CsA blood levels were not
      different between wild-type and apoE-/- recipients. CsA increased total
      cholesterol and low-density lipoprotein, but not high-density lipoprotein dose
      dependently and significantly, but RAD did not affect the lipids. RAD but not CsA
      significantly attenuated neointima formation. CONCLUSIONS: These results suggest
      that RAD at a dose preventing organ rejection may also prevent transplant
      vasculopathy even in the presence of hyperlipidemia.

PMID- 14578748
TI  - Use of candesartan cilexetil decreases proteinuria in renal transplant patients
      with chronic allograft dysfunction.
AB  - BACKGROUND: Posttransplant proteinuria and hypertension are difficult to treat
      after renal transplantation. Therefore, we examined whether candesartan cilexetil
      is effective in reducing urinary protein excretion or in controlling hypertension
      in patients with renal allograft dysfunction. METHODS: Sixty-two renal transplant
      recipients with proteinuria were enrolled in this study. They underwent kidney
      transplantation under cyclosporine or tacrolimus immunosuppression between
      February 1983 and December 1998. Causes of proteinuria were chronic rejection in
      28, glomerulonephritis in 16, cyclosporine or tacrolimus nephrotoxicity in 9, and
      unknown in 9 recipients. The dose of candesartan cilexetil ranged from 4 to 12
      mg/day. Eleven patients with proteinuria who had not been treated with
      candesartan cilexetil constituted a matched control population. RESULTS:
      Hypertension was well controlled by administration of candesartan cilexetil. Both
      systolic blood pressure and diastolic blood pressure significantly decreased from
      141.7+/-14.8 mm Hg to 118.7+/-11.9 mm Hg and 121.2+/-11.6 mm Hg, and from 89.0+/
      13.0 mm Hg to 72.0+/-10.4 mm Hg and 74.9+/-9.4 mm Hg, at 2 months and 1 year
      after administration, respectively. Urinary protein excretion was reduced from
      0.93+/-1.2 g/day to 0.34+/-0.7 g/day and 0.43+/-1.2 g/day at 2 months and 1 year
      after administration, respectively. The levels of creatinine clearance were
      55.7+/-28.9 mL/min before treatment, 50.9+/-24.8 mL/min at 2 months, and 52.6+/
      24.8 mL/min at 1 year after treatment, respectively. There was no clinically
      significant difference between them. Regarding the calcineurin inhibitor levels,
      there was no significant difference between the levels before and 1 year after
      treatment. There was a significant difference in all examinations (systolic blood
      pressure, diastolic blood pressure, proteinuria, and renal function) between the
      patients with and without candesartan at 1 year after treatment. No significant
      adverse effects occurred. CONCLUSIONS: Candesartan cilexetil can effectively
      control hypertension and proteinuria without deterioration in renal allograft
      function. These data suggest that treatment with candesartan cilexetil may be
      useful for maintaining long-term renal allograft function.

PMID- 14578749
TI  - Live-donor liver transplantation for acute-on-chronic hepatitis B liver failure.
AB  - BACKGROUND: The survival results of patients demonstrating acute-on-chronic liver
      failure and undergoing live-donor liver transplantation (LDLT) have been reported
      to be poor. This study evaluates the survival outcomes of patients who underwent
      LDLT using right-lobe liver grafts for acute-on-chronic hepatitis B liver
      failure. METHODS: The study comprised 32 patients who demonstrated acute-on
      chronic hepatitis B liver failure with mean (+/- standard error of mean) Model
      for End-Stage Liver Disease scores of 36+/-1.8. The mean preoperative intensive
      care unit stay was 2.4 days. LDLT using a right-lobe liver graft including the
      middle hepatic vein was performed in all patients. Oral lamivudine 100 mg daily
      was used for hepatitis B prophylaxis. RESULTS: The patients received liver grafts
      that were 52%+/-2% of the estimated standard liver weight. Hospital mortality
      occurred in two patients, and two other patients died on follow-up. At a median
      follow-up of 23 months, both patient and graft survival rates were 88%. The
      survival results were not different from those of 49 patients who underwent right
      lobe LDLT for elective conditions during the same study period (graft
      survival=82%, P=0.55; patient survival=84%, P=0.75). Two (6.3%) patients
      developed hepatitis B virus DNA breakthrough 47 and 53 months, respectively,
      after transplantation, but they remained well after treatment with adefovir.
      CONCLUSION: Right-lobe LDLT is an effective therapeutic option for patients with
      acute-on-chronic hepatitis B liver failure. It results in satisfactory survival
      outcomes comparable to those in patients undergoing LDLT for elective conditions.

PMID- 14578750
TI  - Increasing the donor pool using en bloc pediatric kidneys for transplant.
AB  - OBJECTIVES: En bloc pediatric kidney transplants (EBPKT) are still a subject of
      controversy. The aim of this study was to determine whether acceptable long-term
      graft survival and function can be achieved in EBPKT compared with the transplant
      of single, cadaveric, adult donor kidneys. METHODS: A retrospective review was
      conducted of 66 recipients of en bloc kidneys from cadaveric pediatric donors and
      434 patients who underwent transplantation with a single kidney from an adult
      donor between January 1990 and May 2002 at the authors' hospital. The recipients
      were well-matched demographically. Both transplant groups were analyzed for short
      and long-term performance in terms of transplant outcome and quality of graft
      function. RESULTS: Overall death-censored actuarial graft survival rates at 1 and
      5 years were 89.2% and 84.6% in the adult kidney transplants (AKT) and 83.3% and
      81.1% in EBPKT, respectively (P=0.56). In the EBPKT group, graft function was
      improved over that observed in AKT. Vascular thrombosis was the most common cause
      of graft loss in EBPKT. Acute rejection occurred more frequently in AKT and Cox's
      regression analysis indicated that undergoing an AKT was a predictive factor for
      acute vascular rejection (adjusted risk ratio, 3.8; 95% confidence interval, 1.4
      10.2; P=0.001). CONCLUSIONS: Overall graft survival was similar in both groups,
      vascular complications were the main cause of graft loss in EBPKT, and the EBPKT
      showed excellent long-term graft function and a low incidence of acute rejection.

PMID- 14578751
TI  - A prognostic model for predicting waiting-list mortality for a total national
      cohort of adult heart-transplant candidates.
AB  - BACKGROUND: Current trends in medical management of advanced heart failure and
      transplant medicine and the enactment of a national transplant law forced a
      change toward allocation driven by disease severity. OBJECTIVE: The aim of this
      study was to create a model for predicting waiting-list survival on the basis of
      simple clinical parameters. METHODS: The clinical profiles of all patients
      registered for heart transplantation in Germany in 1997 (n=889) were used as a
      derivation set, and the total German 1998 cohort (n=897) was used as a validation
      set. The model was validated by the c statistic and by comparison of risk
      stratified mortality rates. The validated model was fine tuned by the appropriate
      calibration procedures. The data were first classified into physiologic
      subscores: an urgency score, a left ventricular heart failure score, a right
      ventricular heart failure score, and a systemic heart failure score. A stepwise
      modeling procedure was undertaken using these subscores as factors as well as the
      recipient's age, ABO blood group, and body surface area. RESULTS: The urgency and
      the left ventricular subscore were found to be significantly associated with
      waiting-list mortality. A summary index termed German Transplant Society (GTS)
      score was then calculated on the basis of seven parameters contained in these two
      subscores. The GTS score was able to predict waiting-list mortality risks for the
      1998 cohort: 1-year mortality before transplantation was 71%, 34%, 11% for the
      high, medium, and low risk groups, respectively. CONCLUSION: The use of this
      continuous disease severity index may improve the selection of cardiac transplant
      candidates.

PMID- 14578752
TI  - High urine sIL-6R as a predictor of late graft failure in renal transplant
      recipients.
AB  - BACKGROUND: Chronic allograft nephropathy is an important cause of late renal
      transplant failure. Although numerous studies on cytokines have been carried out,
      the pathogenetic role of cytokines in chronic renal allograft nephropathy remains
      unclear. METHODS: In a retrospective study, the authors compared posttransplant
      plasma and urine cytokine levels (interleukin [IL]-1alpha, IL-1beta, soluble [s]
      IL-1 receptor [R] antagonist [A], IL-2, sIL-2R, IL-3, IL-4, IL-6, sIL-6R, IL-10,
      tumor necrosis factor-alpha, transforming growth factor-beta2, and interferon
      gamma) in 34 matched pairs of patients with or without late graft failure and in
      50 matched pairs with either normal or increased serum creatinine levels and
      continued stable graft function. RESULTS: Twelve and 6 months before late graft
      failure, urine levels of sIL-6R were significantly increased (P=0.003 and P=0.01,
      respectively). Serum creatinine levels were not associated with increased urine
      sIL-6R. CONCLUSION: High urine sIL-6R appears to be predictive of late graft
      failure in renal transplant recipients.

PMID- 14578753
TI  - Long-term outcomes in pediatric renal transplant recipients who survive into
      adulthood.
AB  - BACKGROUND: Long-term results in renal transplant recipients who underwent
      transplantation as children are often buried within the outcomes of adult
      centers, leaving a void in our knowledge regarding this unique cohort. The
      authors aim to describe the long-term outcomes of children who experienced renal
      failure and subsequently underwent transplantation during childhood and who have
      now reached adulthood, with an emphasis on social and economic rehabilitation.
      METHODS: Two hundred seventeen children were identified who underwent
      transplantation between 1967 and 1999. Of those 217174 who were born before
      October 1982 and who would therefore have reached adulthood were selected for
      study. A questionnaire and consent form were sent to the surviving 132 patients
      of this subpopulation. RESULTS: Fifty-seven adult survivors answered the
      questionnaire. No significant differences were found comparing the respondents to
      the nonrespondents. Nearly half of all respondents were severely short and 27%
      were obese. Questionnaire respondents had high rates of hypertension, bone and
      joint symptoms, fractures, hypercholesterolemia, and cataracts. Despite
      significant remaining health issues, 82% of respondents were employed, 95%
      reported their health as "fair" or "good," 61% reported "no" or "minor" physical
      limitations, and 82% described themselves as "just as" or "more content than
      others." Nearly 50% of the respondents were married, and the overwhelming
      majority reported satisfaction in their sexual lives. CONCLUSIONS: Despite a high
      retransplantation rate and the presence of significant morbidity, renal
      transplantation in children can lead to attainment of a productive and satisfying
      life, with a high degree of rehabilitation in adulthood.

PMID- 14578754
TI  - Selection of lowly immunogenic and highly tolerogenic donor and recipient
      allochimeric class I major histocompatibility complex proteins.
AB  - BACKGROUND: Ten different highly polymorphic amino acids (AAs) are located in the
      alpha1 (alpha1h) and alpha2 (alpha2h) helical regions of the class I major
      histocompatibility complex RT1. An rat alloantigen. We examined the potential of
      alpha1h-RT1. An versus alpha2h-RT1. An polymorphic AAs to induce accelerated
      rejection or tolerance of heart allografts. METHODS: The allochimeric alpha1h52
      90n-RT1.Ac and alpha2h148-179n-RT1.Ac cDNAs were produced by the substitution of
      nucleotides encoding recipient RT1.Ac AAs for donor RT1. An AAs. Allochimeric and
      wild-type (WT)-RT1. An proteins were generated in an Escherichia coli expression
      system. RESULTS: A single portal vein administration of 100 mug alpha1h52-90n
      RT1.Ac protein in combination with a 7-day course of oral cyclosporine A (4
      mg/kg) induced tolerance to Brown Norway (BN) (RT1n) heart allografts in PVG
      (RT1c) recipients more effectively than did WT-RT1. An protein; alpha2h148-179n
      RT1.Ac protein was ineffective. However, subcutaneous injection of 100 mug WT
      RT1. An (but neither alpha1h52-90n-RT1.Ac nor alpha2h148-179n-RT1.Ac) protein
      induced accelerated rejection of BN heart allografts. Untreated PVG recipients of
      BN heart allografts displayed activation of both interleukin (IL)-2- and
      interferon-gamma-producing T helper (Th) 1 cells and IL-4- and IL-10-producing
      Th2 cells on days 5, 7, and 14 postgrafting, as measured by an enzyme-linked
      immunospot assay. In contrast, in comparison with rejectors, tolerant recipients
      showed down-regulation of Th1 cells and up-regulation of Th2 cells on days 5, 7,
      14, and 200 postgrafting. Histology of heart allografts showed that tolerant BN
      heart allografts had no evidence of acute or chronic rejection when examined on
      day 100 after transplantation. CONCLUSIONS: The poorly immunogenic alpha1h52-90n
      RT1.Ac allochimeric protein induces tolerance by selective activation of
      regulatory Th2 cells.

PMID- 14578755
TI  - Mesenchymal stem cells inhibit the formation of cytotoxic T lymphocytes, but not
      activated cytotoxic T lymphocytes or natural killer cells.
AB  - BACKGROUND: Mesenchymal stem cells (MSCs) can reduce the incidence of graft
      versus-host disease because of their ability to inhibit T-lymphocyte
      proliferation. There are no publications on the effect that MSCs have on
      cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells, effector cells
      vital for the graft-versus-leukemia effect. METHODS: Cytotoxic T cells were
      primed in mixed lymphocyte culture (MLC) against irradiated stimulator
      lymphocytes, and irradiated third-party MSCs were added at different time points.
      The CTLs were collected, and their cytotoxic potential was analyzed in a chromium
      release assay against the same stimulator cells as in the MLC. Purified NK cells
      were mixed with irradiated MSCs, and the lysis was measured in chromium-release
      assay against K562 target cells. RESULTS: We found that MSCs inhibited CTL
      mediated lysis by 70% if added at the beginning of the 6-day MLC. The lysis was
      not affected on day 3 or in the cytotoxic phase. Furthermore, MSCs inhibited the
      formation of cytotoxic lymphocytes when the cells were separated in a transwell
      system, which indicates that the effect is mediated by a soluble factor. NK cell
      mediated lysis of K562 cells was not inhibited by MSCs. MSCs did not induce
      proliferation of allogeneic lymphocytes, and they were not lysed by allogeneic
      CTLs or NK cells. CONCLUSION: Our findings indicate that MSCs escape recognition
      by CTLs and alloreactive NK cells, and inhibit the formation of cytotoxic T cells
      by secreting a soluble factor, but that they do not interfere with CTLs and NK
      cell lysis.

PMID- 14578756
TI  - Reduction of recipient macrophages by gadolinium chloride prevents development of
      obliterative airway disease in a rat model of heterotopic tracheal
      transplantation.
AB  - BACKGROUND: Recent studies have shown the possible role of growth factors and the
      involvement of macrophages as a source of them in the pathogenesis of
      bronchiolitis obliterans (BO) after lung transplantation. OBJECTIVE: The authors
      intended to determine whether depletion of recipient macrophages by gadolinium
      chloride (GdCl3) resulted in decreased obliterative airway disease (OAD) in a rat
      model of heterotopic tracheal transplantation. METHODS: A tracheal segment of
      donor rats (Brown Norway) was transplanted into a subcutaneous pouch of fully
      major histocompatibility complex-incompatible recipient rats (Lewis). Recipients
      were injected intravenously with 80 mg/kg of GdCl3.6H2O or saline on days 0, 7,
      and 14 posttransplant. Allografts were harvested on days 7, 14, 17, and 21 and
      the degree of OAD resulting from fibroproliferative tissue was pathologically
      scored on a scale of 0 to 4. A portion of allografts was submitted to reverse
      transcriptase polymerase chain reaction analysis to examine mRNA expression for
      platelet-derived growth factor (PDGF), basic fibroblast growth factor, and
      transforming growth factor-beta1. RESULTS: Immunohistochemical studies confirmed
      reduction in the number of ED2+ macrophages in tracheal allografts by GdCl3
      injection. GdCl3 treatment significantly decreased OAD of allografts, with the
      histologic score of 1.4+/-0.3 in the treated animals compared with 3.0+/-0.5 in
      the controls (mean+/-SE, P=0.02) at day 21 posttransplant, and this was
      accompanied by decreased PDGF-A and PDGF-B gene expression in the GdCl3 group at
      day 17 posttransplant. CONCLUSIONS: Macrophage reduction by GdCl3 resulted in
      significantly decreased OAD development and reduced PDGF mRNA expression in
      allografts. This suggests a potential effectiveness of therapies targeting
      recipient macrophages in preventing BO after lung transplantation.

PMID- 14578757
TI  - Natural killer-cell activity after human renal transplantation in relation to
      killer immunoglobulin-like receptors and human leukocyte antigen mismatch.
AB  - BACKGROUND: Natural killer (NK) cells use killer immunoglobulin-like receptors
      (KIR) that bind to self-class I major histocompatibility complex (MHC) molecules
      to prevent killing of autologous cells. Mismatched allografts, which do not
      express recipient MHC class I molecules, can therefore be potential targets for
      NK-cell killing. In our living related-unrelated renal transplantation program,
      donor-recipient pairs vary in the amount of both HLA and KIR genes they share.
      This provides us with a unique opportunity to dissect the influence of KIR on NK
      cell function after transplantation. METHODS: Recipient NK cells were used in a
      cytotoxicity assay against donor peripheral blood mononuclear cells 2 days
      before, on the day of, and 3 days after transplantation. Results were correlated
      to HLA-KIR compatibility between donor and recipient. RESULTS: NK killing, in a
      direct ex vivo setting, was demonstrated to be HLA mismatch dependent. Recipient
      NK antidonor cytotoxicity was unaltered despite having received 2 days' treatment
      with cyclosporine A before transplantation. However, cytotoxicity increased 3
      days after transplantation in 71% of recipients. Recipients exhibiting increased
      NK cytotoxicity against their donors after transplantation were found to possess
      more activating KIR genes specific for donor class I MHC molecules than those in
      whom killing activity did not increase (P<0.04). CONCLUSIONS: NK cells are
      activated after transplantation despite quadruple immunosuppression, suggesting
      that recipient NK-cell cytotoxicity against the donor may be a previously
      unrecognized area of the rejection process, especially in poorly matched donor
      recipient pairs where the recipient may not express the correct repertoire of
      inhibitory receptors to prevent killing of donor cells.

PMID- 14578758
TI  - Is the cytomegalovirus serologic status always accurate? A comparative analysis
      of humoral and cellular immunity.
AB  - BACKGROUND: The precise knowledge of cytomegalovirus (CMV) status is important in
      a variety of clinical settings such as transplantation or blood transfusion.
      There are, however, various situations where an immunoglobulin-based diagnostic
      approach has limitations. METHODS: The CMV status of 388 individuals was
      determined by the analysis of both CMV-specific immunoglobulins and cellular
      immunity using a standard enzyme-linked immunosorbent assay and a rapid-flow
      cytometric approach, respectively. RESULTS: In 386 of 388 individuals, both
      assays yielded concordant results in assigning the CMV status (294 positive and
      92 negative). In 2 of 94 (2.1%) CMV immunoglobulin (Ig) G-negative individuals,
      CMV-specific CD4 T cells were detectable. Repeated testing of the index and
      follow-up samples yielded one positive and one marginally positive IgG titer.
      CONCLUSIONS: Both assays yielded highly concordant results. Thus, the T-cell
      based approach may represent a reliable alternative for defining CMV status in
      any clinical situation where serologic testing is limited by borderline titers or
      by the presence of passively administered antibodies.

PMID- 14578759
TI  - Strong human leukocyte antigen matching effect in nonsensitized kidney recipients
      with high pretransplant soluble CD30.
AB  - The influence of human leukocyte antigen (HLA) matching on graft survival is
      greater in patients with preformed lymphocytotoxic antibodies than in
      nonsensitized patients. Pretransplant serum soluble CD30 (sCD30) affects graft
      outcome independently of presensitization status. The impact of HLA compatibility
      on kidney transplant survival was analyzed in 3980 nonsensitized first cadaveric
      kidney recipients in relation to the pretransplant serum sCD30 content. Although
      HLA compatibility influenced graft outcome only marginally in nonsensitized
      recipients with low sCD30 (at 3 years: P=0.0095; at 5 years: P=0.1033), a strong
      HLA matching effect was observed in nonsensitized recipients with high sCD30 (at
      3 years: P<0.0001; at 5 years: P=0.0001). Nonsensitized patients with high
      pretransplant sCD30 benefit from an HLA well-matched kidney. Patients should be
      tested for sCD30 while on the waiting list for a kidney transplant, and HLA well
      matched kidneys should be allocated to patients with high sCD30.

PMID- 14578760
TI  - Impact of cytochrome p450 3A5 genetic polymorphism on tacrolimus doses and
      concentration-to-dose ratio in renal transplant recipients.
AB  - BACKGROUND: Tacrolimus pharmacokinetic characteristics vary greatly among
      individuals. Tacrolimus is a substrate of cytochrome p450 (CYP), of subfamily
      CYP3A. CYP3A activity is the sum of the activities of the family of CYP3A genes,
      including CYP3A5. Subjects with the CYP3A5*1/*1 genotype express large amounts of
      CYP3A5. Heterozygotes (genotype CYP3A5*1/*3) also express the enzyme. We
      postulated that CYP3A5 polymorphism is associated with tacrolimus pharmacokinetic
      variations. METHODS: CYP3A5 genotype was evaluated in 80 renal transplant
      recipients and correlated with the daily tacrolimus dose and concentration-to
      dose ratio. RESULTS: The frequency of the homozygous CYP3A5*1 genotype
      (CYP3A5*1/*1) was 5%, and 11% of subjects were heterozygous (CYP3A5*1/*3). The
      mean doses required to obtain the targeted concentration-to-dose ratio were
      significantly lower in patients with the CYP3A5*1/*1 genotype. CONCLUSIONS:
      Determination of CYP3A5 genotype is predictive of the dose of tacrolimus in renal
      transplant recipients and may help to determine the initial daily dose needed by
      individual patients for adequate immunosuppression without excess nephrotoxicity.

PMID- 14578761
TI  - C2 monitoring in maintenance renal transplant recipients: is it worthwhile?
AB  - Presently, there is little knowledge regarding cyclosporine (CsA) concentration
      at 2 hr post-dose (C2) monitoring in maintenance patients. This study evaluates
      the actual C2 range in stable renal transplant recipients (who underwent
      transplantation >12 months ago). In addition, we investigated whether
      underexposure or overexposure to CsA (assessed by C2) affects graft function (as
      measured by serum [S]-creatinine). All renal transplant recipients in Norway
      receiving CsA were asked to participate; 1447 fulfilled the criteria. Valid C2
      and CsA trough concentration (C0) measurements were performed in 1032 renal
      transplant recipients (71%) monitored by C0. Target C0 level was 75 to 125
      mumol/L. CsA levels were measured using a Cloned Enzyme Donor Immunoassay method,
      and all analyses were performed in the same laboratory (overall mean [+/-standard
      deviation] CsA C0=112+/-31 mug/L, CsA C2=697+/-211 mug/L [range 81-1580 mug/L],
      CsA dose [mg/day]=208+/-61, CsA dose [mg/kg/day]=2.8+/-1.1, and S
      creatinine=141+/-58 mumol/L). A univariate analysis of variance showed that
      patients with C2 levels between 700 and 800 mug/L (n=203, S-creatinine=136+/-49
      mumol/L) had significantly lower S-creatinine levels compared with patients with
      C2 levels greater than 950 mug/L (n=94, S-creatinine=152+/-56 mumol/L) (P<0.02).
      The same was true for patients with C2 levels less than 450 mug/L (n=95, S
      creatinine 141+/-72 mumol/L) (P<0.05) when compared with patients with C2 levels
      greater than 950 mug/L. There was no significant difference in S-creatinine
      between patients in the low and intermediate C2 group; 666 patients had C0 levels
      in the therapeutic range (75-125 mumol/L). A linear regression showed a
      significant relation between S-creatinine and C2 for these patients (P=0.03). The
      corresponding relation between S-creatinine and C0 was nonsignificant (P=0.3).
      Monitoring of C2 in maintenance patients is a valuable tool to detect
      overexposure to CsA. Until results from prospective studies are available, we
      recommend C0 in the therapeutic range and reduction in CsA in overexposed
      patients, aiming at a C2 value between 700 and 800 mug/L.

PMID- 14578762
TI  - Successful use of a cardiac allograft from tricyclic antidepressant intoxication.

PMID- 14578764
TI  - The living donor.

PMID- 14578763
TI  - Cyclosporine withdrawal in stable renal transplant recipients.

PMID- 14578765
TI  - Becoming a living kidney donor.
AB  - Earlier investigations of attitudes of living kidney donors have been performed
      in retrospect. We saw a need to investigate in depth those motives and feelings
      that are relevant in potential kidney donors. With a phenomenologic approach,
      interviews were performed with 12 potential donors. Seven categories of motives
      were identified: a desire to help, increased self-esteem from doing good deeds,
      identification with the recipient, self-benefit from the relative's improved
      health, mere logic, external pressure, and a feeling of moral duty. In the
      individual, these categories interacted to create a perception of donation being
      the only option.

PMID- 14578766
TI  - Live related renal transplantation: psychological, social, and cultural issues.
AB  - Cadaveric donation rates have remained static, whereas transplant waiting lists
      continue to rise as demand for renal transplants far exceeds supply. One solution
      to bridge the supply and demand gap is to increase live donation. If live
      donation is to increase, it is important to offer evidence-based psychologic and
      social support to ensure that transplant clinical success is not at the cost of
      psychologic and social harm. This article reports the findings of two substantive
      qualitative studies, both examining similar aspects of live donation: study A
      from a psychologic perspective and study B from a social-cultural perspective.
      The findings show that living-related renal donors do not express regret after
      donation and do report enhanced self-esteem. The decision to donate is immediate
      and altruistic for most parents, although some fathers expressed a degree of
      ambivalence. The decision to donate is more difficult and complex for siblings
      and may lead to conflict between family of birth and family of marriage.
      Reciprocity and feelings of obligation did not appear to cause relationship
      difficulties for siblings but were reported by some of the adolescent recipients
      who had received a parental graft, leading to psychologic distress and social
      familial alienation. These two qualitative studies have demonstrated psychosocial
      risks within the live donation process. These risks should be recognized within
      transplant programs and professional care provided to ensure confidential
      presurgery donor and recipient advocacy and continuing psychosocial support for
      the family unit postdonation.

PMID- 14578767
TI  - Should people who donate a kidney to a stranger be permitted to choose their
      recipients? Views of the United States public.
AB  - BACKGROUND: Several transplant centers have begun to accept kidneys donated by
      altruistic living strangers. Many of these centers insist that such donations be
      nondirected, meaning that the donors may not choose their recipients. On the
      other hand, some authors have argued that anonymous donors should be allowed to
      select their recipients. This study was designed to explore public attitudes
      toward this issue. METHODS: Two telephone surveys of US adults, each including
      more than 1000 participants, were conducted. The first asked about the general
      acceptability of allowing altruistic strangers to direct donations, the
      willingness to donate a kidney to a stranger, and the impact of permitting
      directed donation on willingness to give. The second survey asked about the
      acceptability of directed donation to members of specific groups. RESULTS: About
      one quarter of the respondents said they would donate a kidney to a stranger for
      free, and the vast majority of them would donate even if they could not choose
      their recipients. Two thirds would not allow anonymous kidney donors to direct
      their gifts to a member of a specific racial or religious group, but three
      quarters would support kidney donations directed to children. CONCLUSIONS: These
      data support the current policy of several transplant centers that people who
      wish to donate a kidney to a stranger are not permitted to choose their
      recipients on the basis of membership in a racial or religious group. On the
      other hand, theoretical considerations and the results of this study suggest that
      people who wish to donate a kidney only to an unknown child should be permitted
      to do so.

PMID- 14578768
TI  - Is this live-organ donor your patient?
AB  - The transplant community is in the midst of an ethical reflection regarding the
      manner in which live-organ transplantation should be practiced. There is a
      fundamental aspect to be addressed and reaffirmed. It is the doctor-patient
      relationship between the transplant surgeon and the live-organ donor. This
      relationship brings a mutual responsibility to the physician and the donor
      patient to each other, which should not be abrogated by the claim of donor
      autonomy nor the obligation fostered by the recipient's needs. If equipoise is
      not affirmatively achieved in the risk-benefit calculation for the donor and the
      recipient, then sound medical judgment should override all other concerns.

PMID- 14578769
TI  - Living liver donation: a survey of the attitudes of the public in Great Britain.
AB  - BACKGROUND: Living liver donation (LLD) is becoming an accepted way of increasing
      the donor pool for liver transplantation. The procedure is associated with major
      ethical difficulties because there is a significant risk of death to the healthy
      donor. METHODS: We therefore conducted two surveys of the Great Britain
      population to determine their attitudes to LLD. RESULTS: Approximately three
      quarters of the population of 1734 adults aged more than 15 years were supportive
      of LLD. Those in favor were more likely to be men, better educated, and younger.
      Seventy-four percent were supportive of the donor being reimbursed for costs
      incurred in donation, and 19% agreed that the donor should be paid for donation,
      although there was great variation in the amount suggested. Forty-two percent of
      the population believed that a risk of 1:200 or less was acceptable when donating
      to a family member, and only 14% believed that this risk was acceptable when
      donating to a friend. CONCLUSIONS: Most adults in Great Britain are in favor of
      LLD, although more than half believe that a donor risk of mortality of 1:200 is
      acceptable.

PMID- 14578770
TI  - A nondirected kidney donation and its consequences: personal experience of a
      transplant surgeon.
AB  - Until 1996, living kidney donation had been neglected in Germany. To encourage
      potential donors and to convince them that nephrectomy is not too risky for a
      healthy person, the author decided to set an example with a personal nondirected
      donation. This donation, controversially discussed in the public domain,
      nevertheless succeeded in raising the percentage of living donors in Germany from
      4% to 20% of renal transplants. In 1997, the new German Transplant Act prohibited
      nondirected donation. With the aim of allowing nondirected donation as an act of
      Christian charity, a plaint had been submitted to the Constitutional Court
      against that law on the basis that it violated several fundamental rights, but it
      was dismissed because of strong medical opposition. The author experienced some
      unpleasant professional consequences of his act but, nevertheless, is convinced
      that he had taken the right step when deciding to give a kidney to a stranger.

PMID- 14578771
TI  - Part of my liver.

PMID- 14578772
TI  - Living donors: options and meanings.
AB  - Both the phenomenologic study by Lennerling and colleagues and the case study by
      Dwyer raise interesting moral issues. Lennerling et al.'s finding that
      prospective kidney donors understood their decisions as "the only option" invites
      further examination into how donors understand this phrase, because, as
      ordinarily construed, it seems false; other options do exist for patients
      undergoing renal failure. Dwyer's case challenges our moral understanding of
      transplantation at an even deeper level, presenting us with a possible example of
      an instance of organ provision, not as a "gift" to the recipient, but as a
      "shield" for a third party. There is no existing moral consensus that surgeons or
      other health professionals may gravely worsen the health and threaten the lives
      of healthy people on the grounds that someone other than their patients may be
      benefited.

PMID- 14578773
TI  - Magnetic resonance imaging in gynecologic disease.

PMID- 14578774
TI  - Magnetic resonance imaging of mullerian duct anomalies of the uterus.
AB  - Congenital uterine anomalies (mullerian duct anomalies) comprise a spectrum of
      developmental malformations associated with varying degrees of adverse
      reproductive outcomes. Although traditionally diagnosed by hysterosalpingography
      or ultrasound, further elaboration of the findings frequently was performed with
      laparoscopy/laparotomy and hysteroscopy. The need for diagnostic surgical
      intervention has largely been eclipsed with the advent of magnetic resonance
      imaging, which has become the imaging modality of choice for characterization of
      congenital mullerian anomalies.

PMID- 14578775
TI  - Benign myometrial conditions: leiomyomas and adenomyosis.
AB  - Leiomyomas and adenomyosis are common benign myometrial conditions. Although
      their symptoms overlap, traditional treatment of these two entities differs;
      thus, making the correct diagnosis is critical. Specifically, uterine-conserving
      therapy is well established for many women with symptomatic leiomyomas, whereas
      hysterectomy is the treatment for debilitating adenomyosis. Magnetic resonance
      imaging (MRI) is the most accurate modality for identifying leiomyomas and
      adenomyosis. T2-weighted sequences often are diagnostic. For leiomyomas, MRI
      reliably identifies their number, size, and location. These features help triage
      patients to appropriate therapy. For adenomyosis, MRI establishes the diagnosis
      in cases of equivocal or nondiagnostic ultrasounds. MRI also has been used to
      confirm an ultrasound diagnosis of adenomyosis when curative surgery is being
      considered. Intravenous gadolinium chelates are not necessary to make the
      diagnosis of either adenomyosis or leiomyomas, but it provides useful information
      about vascularity of lesions, a factor that may impact the type of treatment
      undertaken.

PMID- 14578776
TI  - Magnetic resonance imaging of benign adnexal disease.
AB  - Magnetic resonance imaging (MRI) plays an important role in localizing and
      characterizing pelvic masses, particularly adnexal masses. The multiplanar
      capability of MRI helps to locate an abnormality outside the ovary and facilitate
      the exclusion of malignancy. Its superior soft-tissue contrast features help to
      diagnose specific benign masses, including teratoma, endometrioma, and ovarian
      fibroma. In addition, cystic ovarian neoplastic lesions can be further
      characterized as benign versus malignant, particularly after gadolinium
      administration. An approach to adnexal evaluation using MRI is discussed based on
      these features.

PMID- 14578777
TI  - Ovarian malignancies.
AB  - Ovarian cancer is the second most common pelvic tumor and the leading cause of
      death from a gynecologic malignancy. MRI plays a strategic role in patient care
      for initial evaluation and treatment planning in patients with ovarian cancer.
      This article reviews the pathologic classification and characteristic findings on
      MRI of ovarian malignancies, patterns of tumor spread and staging, and the
      utility of cross-sectional imaging prior to primary and secondary to
      cytoreproductive surgery.

PMID- 14578778
TI  - Benign and malignant diseases of the endometrium.

PMID- 14578779
TI  - A comparison of the long-term morbidity following deep circumflex iliac and
      fibula free flaps for reconstruction following head and neck cancer.
AB  - Composite free tissue transfer has an established role in head and neck oncology
      for the reconstruction of the bony defect following tumor ablation, and while
      donor-site morbidity is variably reported, there is little consensus on the most
      favorable donor site. The fibula and deep circumflex iliac artery have distinct
      advantages in terms of the volume and length of bone in mandibular
      reconstruction. Few studies have compared their donor-site morbidity. The aim of
      this study was to compare the fibula and deep circumflex iliac artery flaps using
      a review of the case notes and cross-sectional review of patients attending a
      research clinic for validated orthopedic examination and completion of health
      related quality-of-life questionnaires. Between February of 1993 and May of 2001,
      44 fibula free flaps and 73 deep circumflex iliac artery free flaps were
      performed. Ninety-nine case notes and 36 patients were available for review of
      donor-site morbidity. Sixteen patients with fibula flaps and 20 patients with
      deep circumflex iliac artery flaps took part in the clinical examination
      component of the study, which was composed of a clinical examination by an
      orthopedic surgeon using the American Orthopedic Foot and Ankle Society ankle
      scoring system and the Harris hip scoring system, and two patient-completed
      questionnaires, the University of Washington Questionnaire and the Hospital
      Anxiety and Depression Scale. Subjective and objective markers of morbidity
      related to both flaps were similar in most parameters. However, fibula flaps were
      associated with more problems with donor-site healing, reduced power, and
      sensation. Poor orthopedic scores for both flaps were associated with notably
      poor scores on the University of Washington Questionnaire and the Hospital
      Anxiety and Depression Scale. The study would suggest that both deep circumflex
      iliac artery and fibula donor sites result in an acceptable and comparable
      morbidity for most patients, but in cases in which significant donor-site
      morbidity is encountered, health-related quality of life is significantly
      compromised.

PMID- 14578780
TI  - A new method of subcutaneous placement of free jejunal flaps to reconstruct a
      diversionary conduit for swallowing in complicated pharyngoesophageal injury.
AB  - Choking is a serious problem in pharyngoesophageal reconstruction, which may
      occur following tumor ablation of the pharynx or following corrosive injury
      involving the epiglottis and other parts of the upper airway. To prevent choking
      and the risk of severe pulmonary complications, patients have to give up oral
      intake and assume feeding via jejunostomy for the rest of their lives. After
      reconstruction of the esophagus, eight patients experienced frequent choking and
      aspiration. With a free jejunal flap, the inlet for food could be separated from
      the route of the upper airway by a diversion technique. The jejunum segment was
      transferred microsurgically to reconstruct the cervical esophagus, with its inlet
      at the buccogingival sulcus. There were no surgical complications related to
      either the free jejunal flap transfer or the donor site. Postoperatively,
      patients require re-education of their pattern of swallowing, but after the
      rehabilitation period all patients reported a satisfactory oral intake through
      the reconstructed esophagus to the abdomen without choking. There were no
      episodes of aspiration following reconstruction. With this new method to create a
      separate food pathway, patients can resume oral intake safely without choking and
      without permanent jejunostomy. This technique offers a useful solution for
      patients who suffer from recurrent choking and aspiration following injury or
      ablation of the pharynx.

PMID- 14578781
TI  - Dextran-related complications in head and neck microsurgery: do the benefits
      outweigh the risks? A prospective randomized analysis.
AB  - Increased experience with free-tissue transfer has minimized flap loss secondary
      to microvascular thrombosis, yet pharmacologic antithrombotic prophylaxis
      continues to be used routinely. Currently there is no consensus on the ideal
      pharmacologic agent, dosing, or efficacy. Low-molecular-weight dextran has been
      widely used for prophylaxis due to its properties of volume expansion and
      enhanced microrheology. Significant systemic morbidity (pulmonary morbidity,
      cardiac morbidity, anaphylaxis) is known to occur with use of low-molecular
      weight dextran. The purpose of this study was to evaluate morbidity associated
      with postoperative low-molecular-weight dextran and aspirin prophylaxis in head
      and neck microsurgery patients. This study was a randomized prospective analysis
      of 100 consecutive patients undergoing microvascular reconstruction for head and
      neck malignancy during a 2-year period. Patients were randomized into one of
      three postoperative antithrombotic prophylaxis treatment groups: low-molecular
      weight dextran 20 cc/hour for 48 hours (n = 35), low-molecular-weight dextran 20
      cc/hour for 120 hours (n = 32), or aspirin 325 mg/day for 120 hours (n = 27). Six
      patients were excluded intraoperatively due to the need for systemic heparin
      therapy. Treatment groups were compared for age, sex, prior medical problems,
      duration of anesthesia, and intraoperative fluid intake. Flap outcome and the
      incidence of local and systemic complications were evaluated in the treatment
      groups. Patient ages ranged from 12 to 84 years (mean age, 58 years). No
      significant difference was found among the treatment groups with respect to age,
      sex, prior medical problems, duration of anesthesia, intraoperative fluid intake,
      and the distribution of donor and recipient sites. There were no total flap
      losses and two partial flap losses in this series. Three flaps were reexplored
      and all were salvaged. The incidence of systemic complications (congestive heart
      failure, myocardial infarction, pulmonary edema, pleural effusion, and pneumonia)
      was as follows: low-molecular-weight dextran 120 hours, 51 percent; low-molecular
      weight dextran 48 hours, 29 percent; and aspirin, 7 percent. Analysis of these
      data suggests that the method of prophylaxis had no effect on overall flap
      survival. However, the incidence of systemic complications was significantly
      related to the method of prophylaxis, with patients receiving low-molecular
      weight dextran 120 hours and 48 hours at a 7.2 and 3.9 times greater relative
      risk, respectively, of developing a systemic complication compared with patients
      receiving aspirin. The results of this study have eliminated the routine use of
      low-molecular-weight dextran prophylaxis at our institution in an effort to
      reduce morbidity in head and neck microsurgical reconstruction.

PMID- 14578782
TI  - The use of the operating microscope for cleft palate repair and pharyngoplasty.
AB  - Since 1991, the author has used the operating microscope for all palate and
      pharyngeal operations. There are benefits for the surgeon, who operates in a more
      comfortable position with reliable lighting and variable magnification; for
      trainees and operating room staff, who have the same view as the surgeon, either
      through a teaching arm or on a video screen; and, it is hoped, for the patient,
      as the anatomy is more clearly displayed and potentially, therefore, more
      accurately reconstructed.

PMID- 14578783
TI  - A technique for cleft palate repair.
AB  - The author has developed a technique of palate repair that combines minimal hard
      palate dissection with radical retropositioning of the velar musculature and
      tensor tenotomy. The repair is performed under the operating microscope. Results
      are reported for 442 primary palate repairs performed between 1978 and 1992
      inclusive, with follow-up of at least 10 years. In 80 percent of these palate
      repairs, repair was carried out through incisions at the margins of the cleft and
      without any mucoperiosteal flap elevation or lateral incisions. Secondary
      velopharyngeal rates have decreased from 10.2 to 4.9 to 4.6 percent in successive
      5-year periods within this 15-year period. Evidence from independent assessment
      of speech results in palate re-repair and submucous cleft palate repair suggests
      that this more radical muscle dissection improves velar function.

PMID- 14578784
TI  - Distraction osteogenesis in correction of micrognathia accompanying obstructive
      sleep apnea syndrome.
AB  - To evaluate the effect of distraction osteogenesis in correction of micrognathia
      accompanying obstructive sleep apnea syndrome, a total of 28 patients with
      different severities of obstructive sleep apnea syndrome underwent mandibular
      distraction osteogenesis. A total of 51 distraction devices were placed for
      bilateral distraction in 23 patients and for unilateral distraction in five
      patients. The mean age of patients was 21.2 years (range, 3 to 60 years). Eleven
      patients had micrognathia accompanying obstructive sleep apnea syndrome secondary
      to bilateral temporomandibular joint ankylosis, and 10 patients had micrognathia
      accompanying obstructive sleep apnea syndrome secondary to unilateral
      temporomandibular joint ankylosis. Three patients had developmental micrognathia
      accompanying obstructive sleep apnea syndrome. The other four patients had
      micrognathia and concomitant obstructive sleep apnea syndrome induced by trauma,
      infection, or tumor resection. Each patient had been evaluated preoperatively and
      postoperatively with cephalometry and polysomnography. Mandible advancement
      ranged from 9 to 30 mm (average, 20.4 mm) and was successfully achieved after
      distraction. Fine new bone formed in the distraction gap when the distraction
      devices were removed 3 to 4 months after distraction was completed. No infection
      or other complications occurred in any patients. Complete curative effects were
      achieved in nine severe, six moderate, and eight mild obstructive sleep apnea
      syndrome patients after distraction, and the other five patients had been
      improved to the mild level. After distraction was completed, the posterior airway
      space was increased on average from 4.6 mm to 12.5 mm and the sella-nasion-point
      B angle was increased on average from 66 degrees to 75 degrees on cephalometric
      studies. The polysomnographic examination showed that the apnea hypopnea index
      was lowered on average from 58.0 to 3.15, and the lowest oxygen saturation was
      increased on average from 77 percent to 90.3 percent after distraction was
      completed. The follow-up period was 3 to 61 months (average, 18.1 months). The
      curative effect was stable and no relapse occurred. Therefore, the authors
      conclude that mandibular distraction osteogenesis is an effective method for
      correcting micrognathia accompanying obstructive sleep apnea syndrome. Compared
      with other current routine surgical procedures, it has many advantages, such as
      low risk, simple manipulation, high curative rate, low relapse rate, and stable
      result. It is presently the most effective method for the treatment of this
      difficult and complicated disorder.

PMID- 14578785
TI  - Midline (dermoid) cysts of the floor of the mouth: report of 16 cases and review
      of surgical techniques.
AB  - A retrospective review of 16 cases of midline (dermoid) cysts of the floor of the
      mouth is presented, evaluating the different surgical approaches. Sixteen cases
      of patients with a diagnosis of midline cyst of the floor of the mouth, treated
      at the Maxillofacial Surgery Department of the School of Medicine and Surgery of
      the "Federico II" University of Naples (Naples, Italy), were observed over a 10
      year period, between 1988 and 1998; age, sex, localization, diagnostic technique,
      and type of treatment were evaluated. Male patients were more frequently
      affected, with a male-to-female ratio of 3:1 (12:4 cases). Patients ranged in age
      from 5 to 51 years (average age, 27.8 years). The preoperative assessment was
      made using ultrasonography in all cases but one, computed tomography in eight
      cases, and magnetic resonance imaging in three cases. Regarding surgical
      techniques used, a transcutaneous approach was adopted for median geniohyoid
      cysts, an extended median glossotomy technique was used for very large median
      genioglossal cysts, a median glossotomy technique was used for median
      genioglossal cysts, and a midline incision of the oral mucosa along the lingual
      frenulum was used for sublingual cysts. During the postoperative course, there
      were no complications except for modest edema in three cases. Follow-up ranged
      between 24 months and 12 years; no relapses or malignant changes were observed.
      In the authors' experience, the intraoral approach was also effective for the
      treatment of large lesions and led to very good cosmetic and functional results,
      whereas the extraoral incision was necessary only when the cysts were under the
      geniohyoid muscle.

PMID- 14578786
TI  - Perforator-preserving chondrocutaneous rotation flap reconstruction of auricular
      defects.
AB  - A technique of chondrocutaneous flap reconstruction of the ear that preserves the
      perforating branches of the posterior auricular artery is described. Preservation
      of the perforators offers improved safety in high-risk patients because it
      maintains the blood supply to the anterior surface of the ear. This perforator
      preserving technique also emphasizes simplicity of flap design, concealment of
      scars, and preservation of ear shape. It is best suited for reconstructing
      defects of the scapha, antihelix, or triangular fossa up to approximately 2 cm in
      diameter. A variety of chondrocutaneous rotation flaps have been developed for
      reconstructing helical and nonhelical defects. These flaps have been designed on
      the basis of the size and location of the surgical defect. Although previously
      described techniques are usually reliable, extensive dissection and mobilization
      can injure perforators, leading to vascular compromise. When flap reconstruction
      is used in high-risk patients, it is necessary to protect the blood supply, and
      perforator-preserving flap reconstruction offers improved safety. The perforator
      preserving technique was used in six consecutive high-risk patients during a 2
      year period. Good results were obtained in all cases, including in patients who
      smoked cigarettes or had extensive medical problems.

PMID- 14578787
TI  - Vertical versus Wise pattern breast reduction: patient satisfaction, revision
      rates, and complications.
AB  - A prospective, randomized study was designed to compare the outcome of inferior
      pedicle/Wise pattern reduction (group I) with medial pedicle/vertical pattern
      reduction (group II) in moderate resections averaging 500 g per breast. There
      were 105 women in group I and 103 women in group II. All surgical procedures were
      performed by the same plastic surgeon. Patient information recorded included age,
      body mass index, type of surgery, weight of specimen, need for surgical revision,
      and complications. Six months postoperatively the patients were asked to complete
      a questionnaire, which rated their satisfaction with the surgical outcome. The
      questionnaire used a 10-point response format ranging from very disappointed
      (score of 1) to very pleased (score of 10). The results demonstrated that there
      was no significant difference between the groups in age (31 +/- 12 versus 29 +/-
      13 years), body mass index (26 +/- 4 versus 27 +/- 5), and amount of tissue
      excised (553 +/- 203 g versus 548 +/- 205 g). Group I required no surgical
      revisions, but in group II revisions for dog-ears were required in 11 percent.
      The rate of other complications was similar in both groups. Patients' evaluations
      of breast size, shape, symmetry, nipple sensation, symptom relief, ease of
      brassiere/clothing fitting, and overall satisfaction were not significantly
      different. The vertical mammaplasty was ranked significantly (p < 0.05) higher by
      patients in regard to scars (6 +/- 2 versus 3 +/- 3) and overall aesthetic
      results (8 +/- 1 versus 6 +/- 3). In the management of moderate macromastia, this
      study indicates that patients who have a vertical reduction are less disappointed
      with the scars but require a significantly higher rate of surgical revisions
      compared with patients who have a Wise pattern reduction.

PMID- 14578788
TI  - Symmetrical breast reconstruction: is there a role for three-dimensional digital
      photography?
AB  - Clinical applications of three-dimensional digital photography include
      assessments of breast volume and contour. It was hypothesized that knowledge of
      preoperative and postoperative breast volumes might facilitate obtaining symmetry
      after reconstructions with autologous tissue or implants. Breast reconstruction
      was performed for 382 women during a 4-year period. Of those women, 334 completed
      all phases of the reconstruction and underwent symmetry analysis. Reconstructive
      procedures included the use of pedicle transverse rectus abdominis
      musculocutaneous flaps, free transverse rectus abdominis musculocutaneous flaps,
      deep inferior epigastric perforator flaps, superior gluteal artery perforator
      flaps, or latissimus dorsi flaps or expanders/implants. Three-dimensional digital
      photographic images were obtained for 33 women, whereas the remaining 301 women
      were not digitally photographed. The differences in symmetry after the initial
      reconstruction and after the secondary procedures were compared for all women and
      for the groups with and without three-dimensional photographic images. For the
      group with three-dimensional imaging, initial volume symmetry was obtained for 73
      percent, initial contour symmetry was obtained for 27 percent, secondary
      procedures were necessary for 70 percent, final volume symmetry was obtained for
      88 percent, and final contour symmetry was obtained for 79 percent. For the group
      without three-dimensional photographic images, initial volume symmetry was
      obtained for 57 percent, initial contour symmetry was obtained for 34 percent,
      secondary procedures were necessary for 50 percent, final volume symmetry was
      obtained for 80 percent, and final contour symmetry was obtained for 71 percent.
      The results demonstrated that there was no significant difference in final
      contour and volume symmetry between women who had or did not have three
      dimensional digital photographic images taken. However, the results demonstrated
      that autologous tissue reconstructions resulted in improved contour and volume
      symmetry, compared with implant reconstructions.

PMID- 14578789
TI  - Neurovascular territories of the external and internal oblique muscles.
AB  - The purpose of this study was to document the extent of the arteries supplying
      the external and internal oblique muscles and the connections among the vascular
      territories. Ten adult human cadavers underwent whole-body arterial perfusion
      (200 ml/kg) with a mixture of lead oxide, gelatin, and water, through the carotid
      artery. The external and internal oblique muscles were dissected and subjected to
      radiography. The vasculature of each muscle was analyzed by using the paper
      template technique. The areas of the vascular territories of the individual
      intercostal arteries within the external oblique muscle varied from 9 to 22
      percent. The area of the vascular territory of the muscular branch of the deep
      circumflex iliac artery was 5 to 18 percent. The ascending branch of the deep
      circumflex iliac artery supplied a mean of 35.7 percent of the vascular territory
      of the internal oblique muscle. The lower six posterior intercostal arteries
      supplied a mean of 48.5 percent. The lateral branches of the deep inferior
      epigastric artery supplied a mean of 15.8 percent. This information provides the
      basis for the design of external and internal oblique muscle flaps for functional
      muscle transfer.

PMID- 14578791
TI  - Reverse anterior tibial artery flap for reconstruction of foot donor site.
AB  - The foot offers numerous useful options for hand reconstruction. Hallux transfer,
      dorsalis pedis flap, second toe transfers, and toe joint transfers offer good
      functional results in reconstructed hands. However, when the donor site is
      repaired with skin grafts, delayed wound healing, scarring, and contractures
      often result. Poor cosmesis of the donor site and altered gait are the main
      drawbacks of the procedures. The authors propose a new concept of primary
      reconstruction of the donor foot using a reverse-flow anterior tibial flap from
      the same leg. Two flaps are raised from the same anterior tibial vessel system in
      continuity as a distal free flap for hand reconstruction and as a proximal
      reverse-flow pedicled flap to resurface the donor defect. This technique allows
      good flap reconstruction of the foot donor site, reducing morbidity and limiting
      the operation to the same limb. The authors report their experience of 33 cases.
      There were no failures. Primary wound healing was achieved in the foot donor
      site, with acceptable cosmesis and satisfactory function.

PMID- 14578790
TI  - Significance of shoulder function in the reconstruction of prehension with double
      free-muscle transfer after complete paralysis of the brachial plexus.
AB  - Reconstruction of shoulder stability and movement in cases with complete
      paralysis of the brachial plexus was performed to improve the outcomes for
      universal function of prehension after double free-muscle transfer (Doi's
      procedure). In cases in which the C5 or C6 nerve root was available as a donor,
      neurotization of the supra-scapular nerve was performed with a nerve graft. If
      the C5 or C6 nerve root was not available, then the contralateral C7 nerve root
      was chosen as the donor motor nerve and was transferred to the suprascapular
      nerve by using a vascularized ulnar nerve graft. Seven cases with ipsilateral C4,
      C5, or C6 nerve root transfer to the suprascapular nerve and one with
      contralateral C7 transfer were evaluated, and the functional outcomes for the
      range of shoulder motion were compared with those for patients who had undergone
      arthrodesis of the humeroscapular joint or had undergone no procedures for
      shoulder function reconstruction. The patients who underwent supra-scapular nerve
      repair demonstrated statistically significantly better ranges of motion for
      flexion and abduction of the shoulder, compared with the other two groups.
      Shoulder function is important for achieving prehensile function among patients
      with complete paralysis of brachial function, when they undergo double free
      muscle transfer.

PMID- 14578792
TI  - Effect of vascular endothelial growth factor on rat Achilles tendon healing.
AB  - This study evaluated the effect of exogenous vascular endothelial growth factor
      (VEGF) on tendon healing and regulation of other growth factors in a rat Achilles
      tendon model. Fifty Sprague-Dawley rats were used. In the experimental group, the
      left Achilles tendon was transected and repaired with the modified Kessler suture
      technique, and the right Achilles tendon was transected and repaired with
      resection of plantaris tendon. VEGF, 100 mul (50 mug/ml), was injected into each
      tendon at the repair site. The same surgical procedures were performed in the
      control group, with the same volume of saline injected into the repair sites. At
      intervals of 1, 2, and 4 weeks, the animals were killed and the tendons were
      harvested and evaluated for tensile strength (1, 2, and 4 weeks) and gene
      expression (postoperative day 4). At 1 week postoperatively, when plantaris
      tendon was preserved, the tensile strength of the repaired tendons with VEGF
      treatment (3.63 +/- 0.62 MPa) was significantly higher than the tensile strength
      of the repaired tendons with saline treatment (2.20 +/- 0.36 MPa). There was no
      difference in tensile strength between the two groups without the plantaris
      tendon support. At 2 weeks postoperatively, the tensile strength was 11.34 +/-
      3.89 MPa in the group with VEGF treatment and plantaris tendon preservation,
      which was significantly higher than the tensile strength in the other groups.
      There was no significant difference in tensile strength among the groups at 4
      weeks postoperatively. The gene expression showed that transforming growth factor
      beta in the VEGF-treated tendon was up-regulated in the early stage of tendon
      healing, whereas expression of platelet-derived growth factor, basic fibroblast
      growth factor, and insulin-like growth factor-1 was not significantly different
      among the groups. In conclusion, administration of exogenous VEGF can
      significantly improve tensile strength early in the course of the rat Achilles
      tendon healing and was associated with increased expression of transforming
      growth factor-beta.

PMID- 14578793
TI  - Effect of sodium diphenylhydantoin on skin wound healing in rats.
AB  - This study evaluated the effect of phenytoin (sodium diphenylhydantoin) on skin
      wound healing in a rat model. The study was divided into two parts. In part I, 20
      mul of phenytoin (10 mg/ml) was subcutaneously injected into the 3-cm dorsal full
      thickness incisional wounds of 14 rats on postoperative days 0, 3, and 6. Twelve
      rats that received saline injections were used as the controls. The skin samples
      were harvested and tested for tensile strength and histology. An additional 12
      rats with the same incisional wounds were tested for chemokine gene expressions.
      In part II, 20 mul of phenytoin (10 mg/ml) was applied topically once a day on a
      4 x 4 cm area of the open dorsal wounds of 10 rats. Saline was applied to the
      wounds of the 10 control group rats. The wounds were measured weekly. The results
      showed that the average tensile strength of the phenytoin-treated wound was 0.49
      +/- 0.08 MPa compared with the control group at 0.02 +/- 0.01 MPa (p < 0.05). The
      density ratio of chemokine monocyte chemotactic protein (MCP-1) to beta-actin in
      the phenytoin-treated group was also significantly higher than in the control
      group (p < 0.05). Histologic analysis of the phenytoin group showed a large
      amount of fibroblast proliferation, collagen synthesis, and neovascularization.
      Phenytoin-treated wounds were also smaller at 1 to 6 weeks postoperatively than
      the control group wounds. The authors conclude that the administration of
      phenytoin can promote wound healing and significantly increase MCP-1 expression.
      Phenytoin-treated wounds showed significant increase in collagen deposition and
      neovascularization, which resulted in an increased wound tensile strength and
      accelerated healing of both open and closed wounds.

PMID- 14578794
TI  - Biological aspects of limb transplantation: I. Migration of transplanted bone
      marrow cells into recipient.
AB  - The transplanted limb contains bone marrow tissue. The hematopoietic cells
      contained in the bone of the graft normally differentiate after transplantation
      and can be released to the recipient. The cells migrate to the recipient bone
      marrow cavities and lymphoid organs. This causes the immune reaction between the
      donor and the recipient, which develops not only in the graft itself but also in
      the recipient immune organs where donor bone marrow cells home. The purpose of
      this study was to investigate the process of migration of the hematopoietic cells
      from the donor limb to the recipient bone marrow cavities and lymphoid tissues.
      The questions the authors asked were: what is the rate of release of bone marrow
      cells from the transplanted bone, where do the released bone marrow cells home in
      the recipient, how fast are donor bone marrow cells rejected by the recipient,
      and can some bone marrow cells homing in the recipient tissues survive and create
      a state of microchimerism. Experiments were performed on Brown Norway and Lewis
      inbred rat strains (n = 30). Limb donors received intravenous chromium-51-labeled
      bone marrow cells. Twenty-four hours later, the limb with homing labeled bone
      marrow cells was transplanted to an allogeneic or syngeneic recipient. The rate
      of radioactivity of bone marrow cells released from the graft and homing in
      recipient tissues was measured after another 24 hours. To eliminate factors
      adversely affecting homing such as the "crowding effect" and allogeneic
      elimination of bone marrow cells by natural killer cells, total body irradiation
      and antiasialo-GM1 antiserum were applied to recipients before limb
      transplantation. In rats surviving with the limb grafts for 7 and 30 days, homing
      of donor bone marrow cells was studied by specific labeling of donor cells and
      flow cytometry as well as by detecting donor male Y chromosome. The authors found
      that transplantation of the limb with bone marrow in its natural spatial
      relationship with stromal cells and blood perfusion brings about immediate but
      low-rate release of bone marrow cells and their migration to recipient bone
      marrow and lymphoid tissues. Large portions of allogeneic bone marrow cells are
      rapidly destroyed in the mechanism of allogeneic elimination by radioresistant
      but antiasialo-GM1-sensitive natural killer cells. Some transplanted bone marrow
      cells remain in the recipient's tissues and create a state of cellular and DNA
      microchimerism. A low number of physiologically released donor bone marrow cells
      do not seem to adversely affect the clinical outcome of limb grafting. Quite the
      opposite, a slight prolongation of the graft survival time was observed.

PMID- 14578795
TI  - Tissue engineering skin flaps: which vascular carrier, arteriovenous shunt loop
      or arteriovenous bundle, has more potential for angiogenesis and tissue
      generation?
AB  - This study was designed to clarify which vascular carrier, the arteriovenous
      shunt loop or the arteriovenous bundle, has more potential as a vascular carrier
      for an artificial skin flap in rats. An arteriovenous shunt loop was constructed
      between the femoral artery and vein using an interpositional artery (group I) or
      vein (group II) graft. For arteriovenous bundle groups, the femoral artery and
      vein were used and subdivided into two groups: distal ligation type (group III)
      and flow-through type (group IV). The vascular pedicle was wrapped with an
      artificial dermis and implanted beneath the inguinal skin for 4 weeks. For the
      control group, a folded sheet of artificial dermis without any vascular carrier
      was embedded. In experiment 1, the volumes of generated tissue within the
      artificial dermis were measured in the experimental and control groups (n = 5 in
      each group). In experiment 2, the origin of new blood vessels sprouting from the
      arteriovenous shunt loop and arteriovenous bundle were evaluated histologically.
      The volume of generated tissue in the shunt groups was significantly greater than
      that in the bundle groups (p < 0.01). However, the bundle groups also showed a
      great potential for producing new tissue. Serial histological studies showed that
      new capillaries were derived not only from the vasa vasorum of the femoral
      vessels but directly from the femoral vein in both the shunt and the bundle
      groups. This "sprouting" was extensively exhibited in the group III. Although the
      arteriovenous shunt loop showed a greater potential for producing new tissue and
      capillaries, the distal ligation type of bundle was thought to be an effective
      and practical vascular carrier for producing a tissue-engineered skin flap.

PMID- 14578796
TI  - Partial oral duplication: a defect in ectomesenchymal migration?

PMID- 14578797
TI  - Reversed temporal artery island flap for forehead reconstruction.

PMID- 14578798
TI  - Purse-string method for immediate umbilical reconstruction.

PMID- 14578799
TI  - Bridging the generation X gap in plastic surgery training: part 1. Identifying
      the problem.

PMID- 14578800
TI  - Bridging the generation X gap in plastic surgery training: part 2. A proposed
      solution--identifying a "best practice" in a plastic surgery training program.

PMID- 14578801
TI  - Scaphoid nonunion: diagnosis and treatment.
AB  - LEARNING OBJECTIVES: After studying this article, the participant should be able
      to: 1. Understand the anatomy and pathophysiology of scaphoid fractures. 2.
      Understand the risk factors for scaphoid nonunion. 3. Identify treatment options
      for scaphoid nonunion and their respective advantages and disadvantages. 4.
      Identify salvage procedures for scaphoid nonunion advanced collapse of the wrist.
      Scaphoid nonunion is a common but difficult problem for hand surgeons. The
      diagnosis of scaphoid nonunion is often delayed, and therefore, treatment must be
      tailored to the type of fracture, the duration of nonunion, and the presence or
      absence of resulting arthritis. This article reviews the diagnosis and work-up of
      scaphoid nonunion, classification schemes for scaphoid nonunion, and various
      treatment options, including internal fixation, nonvascularized and vascularized
      bone grafting, and salvage procedures.

PMID- 14578802
TI  - Life's lessons from children's athletics: it's more than a game.

PMID- 14578803
TI  - An outcome study comparing intravenous sedation with midazolam/fentanyl
      (conscious sedation) versus propofol infusion (deep sedation) for aesthetic
      surgery.
AB  - The purpose of this study was to determine the differences in measurable outcomes
      following aesthetic procedures performed under intravenous sedation with
      incremental doses of midazolam and fentanyl and those performed under propofol
      infusion. The authors' hypothesis was that the differences in these outcome
      parameters are not significant between these intravenous sedation protocols. All
      intraoperative and perioperative records of 84 consecutive patients having
      aesthetic surgery under a conscious sedation protocol using incremental doses of
      intravenous midazolam and fentanyl were retrospectively reviewed and compared
      with the records of a second group of 85 patients having aesthetic surgery under
      a deep sedation regimen based primarily on propofol infusion. All procedures were
      hospital based and performed by two surgeons. Twenty-eight different parameters
      were examined by chart review. In addition, a patient questionnaire was used to
      assess patient satisfaction and patient recall of operative and perioperative
      pain, anxiety, nausea, and vomiting. Multivariate statistical analysis was
      conducted. The two sedation groups were similar with regard to aesthetic
      procedures performed and patient demographics. The mean duration of operative
      time was statistically equivalent (152 minutes and 153 minutes). In both groups,
      there were minor adverse intraoperative events reported but no significant
      complications. Transient hypotension was more common in the propofol infusion
      group (12.9 percent versus 2.4 percent, p = 0.018), but no patient required
      intervention beyond reducing the sedative agent or increasing intravenous fluids.
      The amount of supplemental fentanyl given intraoperatively was significantly
      higher in the group whose primary agent for sedation was propofol infusion than
      the group who received midazolam/fentanyl (209 mug and 143 mug, respectively).
      The overall questionnaire response rate was 80 percent for both groups. The
      midazolam/fentanyl sedation group had more recall of "unpleasant intraoperative
      events" (17 percent versus 3 percent, p = 0.007). However, both groups had low
      recall of intraoperative pain, anxiety, and nausea. The propofol infusion group
      experienced significantly more nausea in the recovery room (p = 0.002), nausea at
      the time of discharge (p = 0.009), and nausea the evening after the operation (p
      = 0.013). Greater than 90 percent of the patients in both groups would have the
      same anesthetic in the future rather than undergo general anesthesia. Patient
      safety, outcomes, and satisfaction are similar in plastic surgery procedures
      performed under sedation protocols using either incremental doses of midazolam
      and fentanyl or propofol infusion. All operative and postoperative outcomes for
      pain, anxiety, and vomiting were similar in the two groups except for immediate
      postoperative nausea, which was higher in the propofol infusion group. The
      overall satisfaction of patients undergoing plastic surgery procedures under
      these intravenous sedation protocols appears very high.

PMID- 14578805
TI  - Correction of intrinsic nasal tip asymmetries in primary rhinoplasty.
AB  - Preoperative nasal analysis for the rhinoplasty patient is not complete without
      recognition and characterization of asymmetries. A simplified classification of
      columellar and intrinsic nasal tip asymmetries has evolved from 15 years'
      experience with rhinoplasty. Nasal tip asymmetries have vertical and horizontal
      dimensions. The vertical, or cephalocaudal, causes of tip asymmetry are primarily
      extrinsic factors. Elements that contribute to tip asymmetry and are extrinsic to
      the lower lateral cartilages are the bony and cartilaginous septum, the nasal
      bones, the upper lateral cartilages, and the maxilla. Horizontal or side-to-side
      asymmetries can be the result of intrinsic lower lateral cartilage abnormalities.
      The importance of this distinction is to differentiate the patient with a
      deviated nose and concomitant tip asymmetry from the patient with an isolated,
      intrinsic deformity of the nasal tip cartilages. A simplified classification
      system for nasal tip asymmetries is presented along with proposed methods for
      surgical correction. Case examples are analyzed also. A description of
      nondestructive suturing techniques and cartilage grafts to restore nasal tip
      symmetry is provided for each deformity. An open rhinoplasty approach is
      advocated in all cases.

PMID- 14578804
TI  - Intracapsular allogenic dermal grafts for breast implant-related problems.
AB  - Despite advances in surgical techniques and breast implant design, certain
      problems unique to breast implant surgery remain. The historically most onerous
      problem, capsular contracture, is relatively uncommon now. However, problems
      related to thin capsules and periprosthetic atrophy are becoming more common;
      these problems include rippling, symmastia, implant malposition, and bottoming
      out. Options for treatment of these conditions remain extremely limited,
      particularly with saline implants. Allogenic dermal grafting provides one
      satisfactory option. Techniques for use of allogenic dermal grafts and early
      results from 10 patients are summarized in this article, along with histologic
      analysis confirming viability of the grafts at 6-month follow-up in one patient.
      No graft-related complications were identified.

PMID- 14578806
TI  - Pseudoherniation of the buccal fat pad: a new clinical syndrome.

PMID- 14578807
TI  - Do cosmetic breast implants cause suicide?

PMID- 14578808
TI  - Who's who?

PMID- 14578809
TI  - Epidural anesthesia as a technique to control spasticity after surgery in a
      patient with spinal cord injury.

PMID- 14578810
TI  - Fingertip reconstruction using a duplicated thumb by means of the palmar pocket
      method in a child.

PMID- 14578811
TI  - Rare reaction to recombinant erythropoietin.

PMID- 14578812
TI  - Giant keratinous cyst of the lower extremity.

PMID- 14578813
TI  - Inexpensive, compact fluid warmer.

PMID- 14578814
TI  - Chronic, nonhealing, lower extremity ulcers responsive to splenectomy in a
      patient with thalassemia major.

PMID- 14578816
TI  - An obtrusive hand deformity of a musician: the abducted fifth finger.

PMID- 14578815
TI  - "What's in a name?".

PMID- 14578817
TI  - What we as plastic surgeons owe to war.

PMID- 14578818
TI  - The unique advantages of spray-aerosol form of povidone-iodine in plastic surgery
      procedures.

PMID- 14578819
TI  - Use of arthroscopic camera equipment during rhinoplasty.

PMID- 14578820
TI  - Meshing technique in mucosal advancement flaps for vermilionectomy defects.

PMID- 14578821
TI  - Staged tie-over dressing technique.

PMID- 14578822
TI  - Use of a grid to simplify botulinum toxin injection for axillary hyperhidrosis.

PMID- 14578823
TI  - Bloodless pedicle deepithelialization in reduction mammaplasty.

PMID- 14578824
TI  - A training model for designing flaps for release of syndactyly.

PMID- 14578825
TI  - A new idea to avoid complications at the donor site of the wrap-around flap with
      a tissue expander.

PMID- 14578826
TI  - Trichoblastoma trichoepiteliomatosum of the scalp.

PMID- 14578827
TI  - Pediatric emergency medicine research: a critical evaluation.
AB  - OBJECTIVE: A measure of research activity is an important way to gauge knowledge
      advances. We designed this study to analyze trends in pediatric emergency
      medicine (PEM) research, particularly focusing on the amount of research
      presented, topics investigated, location of research presentation, study design,
      and use of statistical analysis. METHODS: Every abstract presented between
      January 1987 and December 1999 from 4 national scientific meetings [Ambulatory
      Pediatric Association (APA), American Academy of Pediatrics (AAP), American
      College of Emergency Physicians (ACEP), and Society for Academic Emergency
      Medicine (SAEM)] was evaluated. Those abstracts that met study criteria were
      evaluated for research topic, year of presentation, and sponsoring organization.
      Abstracts from the first and last 5 years of the study period were assessed for
      study design and use of statistical analysis. Trends over time were examined.
      RESULTS: There were 1675 abstracts presented over the 13-year study period: 41%
      at APA, 27% at AAP, 7% at ACEP, and 25% at AEM. Medical topics were most
      frequently investigated (36%) followed by trauma (20%), administrative (17%),
      procedural (14%), life-threatening emergencies (12%), and surgical (3%). Two
      percent of abstracts was presented in the first year and the greatest proportion
      (14%) was presented in 1999 (P < 0.001). Eighty percent of the abstracts was
      assessed for study design and use of statistics. There was no change in the
      proportion of abstracts that were prospective [odds ratio (OR) = 0.98 (95%
      confidence interval (CI) = 0.76-1.26)] or analytic [OR = 1.06 (95% CI = 0.83
      1.35)] between the early and the later years. Descriptive surveys increased in
      frequency from the early to the later years [OR = 1.92 (95% CI = 1.29-2.92)] as
      did multicentered clinical trials [OR = 7.71 (95% CI = 1.97-66.38)]. Case series
      decreased in frequency [OR = 0.71 (95% CI = 0.54-0.93)] as did bench research [OR
      = 0.21 (95% CI = 0.11-0.40)]. The use of statistics increased with time [OR =
      1.99 (95% CI = 1.54-2.58)] as did the use of CIs [OR = 4.40 (95% CI = 2.76
      7.29)]. CONCLUSIONS: There was a substantial increase in the amount of research
      conducted in PEM. The topics investigated correspond to national recommendations.
      There was not an increase in the amount of research that was prospective or
      analytic in nature; however, there was increased statistical sophistication with
      time.

PMID- 14578828
TI  - Development of a clinical severity score for preseptal cellulitis in children.
AB  - PURPOSE: There is a need for a valid and reliable method to describe the severity
      of preseptal cellulitis. METHODS: Items of a scoring system were derived by an
      expert group and evaluated using a retrospective chart review. The results were
      used to construct the final Severity Index. Validity and reliability of the
      Severity Index was evaluated by prospective assessment of 17 children. The
      Severity Index was compared with a Global Score, a score based on clinical
      impression. RESULTS: The average Severity Index score was 2.0 for patients
      treated with oral antibiotics alone and 6.0 for patients treated with intravenous
      antibiotics. The Severity Index correlated well with the Global Score (Spearman
      rank correlation coefficient rS = 0.60, P = 0.01). Ranked clinical photographs of
      preseptal cellulitis correlated moderately to the Severity Index (rS = 0.66, P =
      0.02). The Severity Index score after 24 hours of treatment was significantly
      lower than at presentation (P = 0.004). The agreement between paired Severity
      Index scores [intraclass correlation coefficient (ICC) = 0.80, P = 0.001] was
      better than the agreement between paired Global Scores (ICC = 0.45, P = 0.03).
      CONCLUSIONS: The Severity Index is an objective clinical tool for evaluating
      severity of preseptal cellulitis in children. It correlates well with clinical
      constructs for severity and is sensitive to small changes in clinical status. It
      has better reliability than overall clinical impression. The Severity Index will
      also be valuable as an outcome measure for future therapeutic trials for
      preseptal cellulitis in children.

PMID- 14578829
TI  - Penetrating neck injuries in children: a retrospective review.
AB  - OBJECTIVE: Penetrating Neck Injuries (PNI) are uncommon in the pediatric
      population, but they constitute a significant management challenge. Literature
      has been scant regarding the evaluation and treatment of such injuries in
      children. Our objective is to evaluate if physical examination alone is
      sufficient in the assessment and management of pediatric PNI. DESIGN:
      Retrospective chart review. SETTING: Pediatric emergency center of an urban
      emergency department (ED) and level 1 trauma center (TC). PARTICIPANTS: All
      patients 16 years or younger that had penetrating neck injuries between January
      1995 and June 2000. INTERVENTIONS: None. RESULTS: During the study period, a
      total of 148,000 and 9900 patients were seen in the pediatric ED and the TC,
      respectively. Thirty-one children (22 males, 9 females) with PNI were identified.
      The median age was 9.5 years (range of 10 months to 16 years). Most children
      (81%) with PNI were evaluated in the TC. Motor vehicle crashes accounted for 32%
      of PNI and gun shot wounds for 23% of cases. Most PNI (84%) occurred in zone II
      of the neck. Eight patients underwent surgical exploration (25.8%) for platysmal
      penetration, none of which revealed any vascular injuries. Only 4 patients had
      barium swallows performed based on physical examination findings. All barium
      swallows were normal. There were no angiograms performed during the study period.
      A total of 3 patients died (mortality rate of 9%), all of which had major
      physical examination findings. CONCLUSION: PNI are infrequent in the pediatric
      population. Most of the patients in our review presented with minor physical
      examination findings and did not require exploration or diagnostic studies.
      Observation of the stable child in our case series was found to be an acceptable
      choice of management of PNI. Further prospective studies are needed to validate
      these results.

PMID- 14578830
TI  - Sepsis workup in febrile infants 0-90 days of age with respiratory syncytial
      virus infection.
AB  - OBJECTIVES: To ascertain the incidence, determinants, and outcome of sepsis
      workup in febrile infants aged 0-90 days with respiratory syncytial virus (RSV)
      infection. DESIGN: Retrospective chart review. RESULTS: 191 infants with RSV,
      21.5% younger than 28 days, were identified; 101 (52.9%) were febrile and 90 were
      afebrile. Among the febrile infants, 84.2% had blood cultures, 68.3% had urine
      cultures, and 58.4% had lumbar punctures. Complete sepsis workup was done in
      52.5% of the febrile cohort, including 77.3% of those aged less than 28 days.
      There were 5 cases of urinary tract infection (UTI) [7.2%, 95% confidence
      interval (CI) = 2.4-16.1] and 1 case of bacteremia (1.2%, 95% CI = 0.0-6.4) among
      the tested febrile patients. There was no case (0%, 95% CI = 0.0-6.1) of
      meningitis. Age, maximum temperature, irritability, apnea, decreased intake,
      chest x-ray findings, and white blood cell count were not predictive of a
      positive culture. Only 7.8% of the afebrile patients had complete sepsis workup.
      Fever [risk ratio (RR) = 5.8, 95% CI = 2.8-12], absence of wheezing (RR = 2.1,
      95% CI = 1.3-3.6), and age less than 28 days (RR = 1.6, 95% CI = 1.2-2.2) were
      independent predictors of complete sepsis workup. Overall, complete sepsis workup
      was associated with a higher rate of antibiotic use (RR = 10.7, 95% CI = 4.9
      23.4), increased hospitalization (RR = 2.1, 95% CI = 1.0-4.7), and prolonged
      hospital stay (median of 2 days vs. 1 day, P = 0.003) compared with those without
      complete workup. CONCLUSION: Considerable variability exists in the sepsis workup
      of febrile infants with suspected RSV infection at our site. Concomitant UTIs are
      common in febrile, RSV-infected infants.

PMID- 14578831
TI  - Emergency department presentation of pediatric stroke.
AB  - Pediatric stroke is not a common occurrence. When compared with adults, the
      pediatric population has a much more diverse group of risk factors, and while
      numerous rare congenital disorders are possible, most known etiologies are
      cardiac, vascular, or hematologic. The emergency department (ED) presentation of
      pediatric stroke does not differ greatly from that of adults, although posterior
      circulation ischemia is less common, and neurologic findings may be more
      difficult to recognize. ED treatment is also largely the same, with an attention
      to resuscitation and avoidance of hypoxia, hypotension, hyperthermia, and changes
      in blood sugar. Use of specialized agents such as aspirin and heparin should be
      considered in certain cases. It is important for the emergency physician to
      recognize acute neurologic events in pediatric patients to minimize
      complications.

PMID- 14578832
TI  - High-dose rectal midazolam for pediatric procedures: a randomized trial of
      sedative efficacy and agitation.
AB  - OBJECTIVES: To compare 2 doses of rectal midazolam, used for pediatric emergency
      department sedation, with regard to sedative efficacy and frequency of
      paradoxical agitation. METHODS: Children <or=48 months old undergoing cutaneous
      procedures received midazolam by rectum, randomized in double-blind fashion to
      standard (0.5 mg/kg, SDM) or high (1 mg/kg, HDM) doses. Behaviors were scored on
      a 5-point sedation scale before and during procedures. Proportions manifesting
      successful sedation and postprocedure agitation were compared between the 2
      doses. RESULTS: Sixty-five patients (32 SDM, 33 HDM) underwent sedated procedures
      (repair of lacerations, 97%). Behavior scores improved for both groups following
      medication administration and at best sedation during procedure. HDM produced
      better sedation at time of first suture (successful sedation: 70%, SDM vs. 91%,
      HDM; intergroup difference = 21%; 95% confidence interval [CI] = 2, 41) and at
      best point during the procedure (72%, SDM vs. 97%, HDM; Delta = 25%; 95% CI = 8,
      43). However, sedative efficacy declined such that only 50% and 73% of the SDM
      and HDM groups, respectively, had successful sedation at the worst point during
      the procedures. Postprocedure agitation occurred in 17% of patients (6%, SDM vs.
      27%, HDM; Delta = 21%; 95% CI = 3, 39). CONCLUSIONS: Rectal midazolam improved
      sedation scores over preprocedure levels and was more effective with a dose of 1
      mg/kg than with 0.5 mg/kg. However, inadequate sedation in 27-50% of patients and
      prolonged agitation in 27% of patients at higher doses counter the advantages of
      rectal midazolam.

PMID- 14578833
TI  - Unilateral pulmonary edema: an uncommon presentation of poststreptococcal
      glomerulonephritis.

PMID- 14578834
TI  - Traumatic diaphragmatic rupture in a pediatric patient: a case report.
AB  - Diaphragmatic rupture following blunt abdominal trauma is an uncommon life
      threatening injury in children. In addition to its high mortality rate, there is
      a significant amount of morbidity associated with this injury. Emergency medicine
      physicians must maintain a high index of suspicion for diaphragmatic rupture and
      its associated complications when evaluating victims of blunt abdominal trauma.

PMID- 14578835
TI  - Gastric trichobezoar: an important cause of abdominal pain presenting to the
      pediatric emergency department.
AB  - Abdominal pain is a common presenting complaint of children seen in urgent care
      settings. It is the manifestation of a wide variety of disease processes ranging
      from benign to immediately life-threatening. Gastric bezoars are among the
      etiologies of chronic childhood abdominal pain that, when undiagnosed, may result
      acutely in serious complications, including gastric ulceration, bleeding and
      perforation, intussusception, and small bowel obstruction. To reinforce the
      importance of including this entity in the differential diagnosis of abdominal
      pain, we present the case of a 10-year-old girl with a history of chronic
      epigastric complaints who was ultimately presented with acute small bowel
      obstruction following fragmentation and distal migration of her gastric
      trichobezoar. Finally, we review and briefly summarize the current literature
      regarding the etiology, diagnosis, and management of this disorder in children.

PMID- 14578836
TI  - Atrial fibrillation in an adolescent--the agony of ecstasy.
AB  - Ecstasy (MDMA), a popular drug of abuse among teenagers, is thought to be
      "relatively" safe. A case of atrial fibrillation following the ingestion of
      ecstasy in a previously well adolescent is presented. Emergency room physicians
      should consider ecstasy abuse in the differential diagnosis of young patients
      presenting with atrial fibrillation.

PMID- 14578837
TI  - Cutaneous larva migrans.
AB  - Cutaneous larva migrans is occasionally seen in pediatric emergency outpatient
      care settings. It results from infestation of hookworm larvae into the epidermis.
      The infestation is self-limited but may produce severe discomfort. The diagnosis
      relies entirely on clinical findings. Laboratory findings only support the
      clinical diagnosis but do not confirm it. Treatment is typically with topical
      thiabendazole, but oral thiabendazole may be indicated in severe cases.

PMID- 14578838
TI  - Evisceration through multiple abdominal wall defects following blunt abdominal
      injury.
AB  - We report an unusual case of a posttraumatic evisceration of small and large
      bowel through 2 holes in the anterior abdominal wall after a motor vehicle
      accident. Prompt adequate management consists of reestablishing the perfusion of
      the eviscerated organ if the blood supply is compromised, performing a full
      laparotomy to exclude intra-abdominal organ injury and meticulous cleaning of the
      eviscerated organs before reducing them in the abdomen and closing the abdomen in
      layers.

PMID- 14578839
TI  - Corticosteroids in acute asthma: past, present, and future.

PMID- 14578840
TI  - Pediatric emergency medicine: legal briefs.

PMID- 14578841
TI  - Nineteen-month-old eating sunflower seeds.

PMID- 14578842
TI  - Coaxing the consultant.

PMID- 14578843
TI  - Off-pump coronary artery bypass surgery.

PMID- 14578844
TI  - Exploring the biological basis of hepatitis B e antigen in hepatitis B virus
      infection.
AB  - The function of the hepatitis B e antigen (HBeAg) is largely unknown because it
      is not required for viral assembly, replication, or infection. In this report we
      chronicle clinical and experimental studies in an attempt to understand the role
      of HBeAg in natural infection. These studies largely have focused on clinical
      pathologic features of HBeAg-negative variants in acute and chronic HBV
      infection, mutational analysis in animal models of hepadnavirus infection, and
      the use of transgenic murine models. The clinical and experimental data suggest
      that serum HBeAg may serve an immunoregulatory role in natural infection. To the
      contrary, cytosolic HBeAg serves as a target for the inflammatory immune
      response. These dual roles of the HBeAg and its ability to activate or tolerize T
      cells show the complexity of the interactions between the HBeAg and the host
      during HBV infection.

PMID- 14578846
TI  - Cardiac dysfunction in spontaneous bacterial peritonitis: a manifestation of
      cirrhotic cardiomyopathy?

PMID- 14578847
TI  - E1 therapeutic vaccination for chronic hepatitis C: all that glitters is not
      gold.

PMID- 14578848
TI  - Establishment, characterization, and long-term maintenance of cultures of human
      fetal hepatocytes.
AB  - Cultured human hepatocytes have broad research and clinical applications;
      however, the difficulties in culturing rodent and human hepatocytes are well
      known. These problems include the rapid loss of the hepatocytic phenotype in
      primary culture and the limited replicating capacity of the cultured cells. We
      describe the establishment of serum-free primary cultures of human fetal
      hepatocytes (HFHs) that retain hepatocytic morphology and gene expression
      patterns for several months and maintain sufficient proliferative activity to
      permit subculturing for at least 2 passages. Initially, HFH cultures contained 2
      main cell types that morphologically resembled large and small hepatocytes. The
      fetal hepatocytes expressed alpha-fetoprotein (AFP), cytokeratin (CK) 19,
      albumin, and other hepatic proteins. Treatment of the cultures with oncostatin M
      (OSM) increased cell size and enhanced cell differentiation and formation of bile
      canaliculi, probably through an effect on hepatocyte nuclear factor (HNF) 4alpha.
      Approximately 1 month after plating, multiple clusters of very small cells became
      apparent in the cultures. These cells had very few organelles and are referred to
      as blast-like cells. Flow cytometric analysis of these cells showed that they
      express oval cell/stem cell markers such as CD90 (Thy-1), CD34, and OV-6 but do
      not stain with antibodies to beta(2)-microglobulin. HFH cultures maintained for 9
      to 12 months produced grossly visible organoids containing ductular structures
      that stained for CK18, CK19, and AFP. In conclusion, HFH cultures, which might
      contain a population of hepatic stem cells, constitute an excellent tool for a
      variety of studies with human hepatocytes, including the mechanisms of viral
      infection.

PMID- 14578849
TI  - Adenovirus-mediated overexpression of follistatin enlarges intact liver of adult
      rats.
AB  - Under normal physiologic conditions, liver size is under strict regulatory
      control. Activin, a member of the transforming growth factor beta (TGF-beta)
      superfamily, is expressed in the intact adult liver and is an inhibitor of
      hepatocyte growth. However, the exact role played by endogenous activin in
      maintaining the size of a normal adult liver has yet to be completely examined in
      vivo. Here, we report the development of an adenoviral vector (AdexCAFS288) that
      expressed human follistatin-288, which binds to activin and neutralizes its
      biologic activities. AdexCAGFP, a control virus, expressed green fluorescent
      protein. AdexCAFS288 effectively expressed follistatin-288, as measured both in
      HepG2 cell lysate and conditioned medium and blocked activin signaling and its
      biologic functions in vitro. Intraperitoneal injection of AdexCAFS288 in vivo
      resulted in significant liver growth (146% of control) in intact liver of adult
      male rats 12 days following treatment without significant dysfunctions. The
      increase in liver size was attributed to increased hepatocyte proliferation, as
      monitored by the mitotic index. Furthermore, there was a significant correlation
      between serum follistatin levels and liver weight. In conclusion, our results
      suggest that activin plays a critical role in maintaining optimal liver size and
      implicates the endogenous activin system as a therapeutic target in the treatment
      of liver disease.

PMID- 14578850
TI  - Role of Valpha 14 NKT cells in the development of impaired liver regeneration in
      vivo.
AB  - Although we have previously demonstrated that IL-12 stimulation increases the
      number of hepatic natural killer (NK) T (NKT) cells and enhances liver injury
      during the early phase of liver regeneration, the role of NKT cells has remained
      unknown. We therefore evaluated the influence of NKT cells activated by IL-12 or
      by alpha-galactosylceramide (alpha-GalCer) on murine liver regeneration using
      Valpha 14 NKT knockout (Jalpha 281(-/-)) mice. Levels of serum alanine
      aminotransferase (sALT) 24 hours after partial hepatectomy were enhanced in
      Jalpha 281(+/+) but not in Jalpha 281(-/-) mice by both procedures. Hepatic NKT
      cells expressed considerably more interferon (IFN) gamma and tumor necrosis
      factor alpha (TNF-alpha) messenger RNA (mRNA) after stimulation with both factors
      in Jalpha 281(+/+) mice. Either anti-IFN-gamma or TNF-alpha antibody inhibited
      the enhancement of liver injury. Furthermore, recombinant TNF-alpha injection
      similarly caused injury in hepatectomized livers of both Jalpha 281(+/+) and
      Jalpha 281(-/-) mice; indeed, adoptively transferred TNF-alpha(+/+) NKT cells
      enhanced liver injury after hepatectomy in TNF-alpha knockout mice. TNF receptor
      expressions on hepatocytes increased and peaked 24 hours after partial
      hepatectomy. In conclusion, simultaneous TNF-alpha synthesis and high levels of
      TNF receptor expression on hepatocytes cause severe liver damage by activated NKT
      cells during liver regeneration.

PMID- 14578851
TI  - Gap junction-mediated intercellular communication in a long-term primary mouse
      hepatocyte culture system.
AB  - Gap junction-mediated intercellular communication (GJIC) is critical for
      maintaining integral cellular processes including differentiation and growth
      control. The disruption of GJIC has been correlated with aberrant function in
      many cell types, including hepatocytes in vivo; therefore it is imperative that
      cellular model systems support intercellular communication to simulate normal
      cellular functions. Functional GJIC has been shown in long-term primary rat
      hepatocyte cultures, which have been implemented widely to study various aspects
      of hepatocellular function; however, the onset of transgenic technology in murine
      species has necessitated the development of a primary mouse hepatocyte system. In
      this report, we analyze GJIC in a dimethylsulfoxide (DMSO)-containing long-term
      primary mouse hepatocyte culture system. The cells retain morphologic and
      biochemical characteristics of differentiated hepatocytes through day 30 post
      plating, including liver-specific gene expression. We further show that
      connexin32 and connexin26 expression and gap junction plaque formation increase
      over time in culture concomitant with an increase in GJIC between adjoining
      primary mouse hepatocytes. In conclusion, the findings described in this study
      make it possible to maintain differentiated primary mouse hepatocytes that also
      show GJIC in long-term culture for 30 days. In addition, this system has the
      potential to be extended to study primary mouse hepatocytes isolated from
      genetically engineered mice.

PMID- 14578852
TI  - Alcohol-induced liver injury in mice lacking Cu, Zn-superoxide dismutase.
AB  - Because alcoholic liver disease has been linked to oxidative stress, we
      investigated the effect of a compromised antioxidant defense system, Cu, Zn
      superoxide dismutase (Sod1) deficiency, on alcohol-induced liver injury.
      C57BL/129SV wild-type (Sod1(+/+)) and Sod1 knockout (Sod1(-/-)) mice were fed
      dextrose or ethanol (10% of total calories) liquid diets for 3 weeks. Histologic
      evaluation of liver specimens of Sod1(-/-) mice fed ethanol showed the
      development of liver injury ranging from mild to extensive centrilobular necrosis
      and inflammation. Sod1(+/+) mice fed ethanol showed mild steatosis; both
      Sod1(+/+) and Sod1(-/-) mice fed the dextrose diet had normal histology. Alanine
      transaminase levels were significantly elevated only in Sod1(-/-) mice fed
      ethanol. Cytochrome P450 2E1 (CYP2e1) activity was elevated about 2-fold by
      ethanol in Sod1(+/+) and Sod1(-/-) mice. Ethanol consumption increased levels of
      protein carbonyls and lipid peroxidation aldehydic products in the liver of Sod1(
      /-) mice. Hepatic adenosine triphosphate (ATP) content was reduced dramatically
      in Sod1(-/-) mice fed ethanol in association with a decrease in the mitochondrial
      reduced glutathione (GSH) level and activity of MnSOD. Immunohistochemical
      determination of 3-nitrotyrosine (3NT) residues in liver sections of the Sod1
      knockout mice treated with ethanol showed a significant increase of 3NT staining
      in the centrilobular areas. In conclusion, a rather moderate ethanol consumption
      promoted oxidative stress in Sod1(-/-) mice, with increased formation of
      peroxynitrite, protein carbonyls, and lipid peroxidation and decreased
      mitochondrial GSH and MnSOD. We speculate that the increased oxidative stress
      causes mitochondrial damage and reduction of ATP content, leading to alcoholic
      liver injury. This model may be useful in further mechanistic studies on alcohol
      induced liver injury.

PMID- 14578854
TI  - Oxidative stress-mediated down-regulation of rat hydroxyacid oxidase 1, a liver
      specific peroxisomal enzyme.
AB  - Hydroxyacid oxidase 1 (Hao1) is a liver-specific peroxisomal enzyme that oxidizes
      glycolate to glyoxylate with concomitant production of H2O2. In Hao1 messenger
      RNA (mRNA), an iron-responsive element (IRE) homologous to the sequence
      recognized by iron regulatory proteins (IRP), key regulators of iron homeostasis,
      is present, but the involvement of iron in Hao1 regulation remains unclear. In
      this study, we found a reduction of Hao1 mRNA content in livers of rats with
      chronic dietary iron overload, which showed decreased IRP activity and higher
      ferritin expression as expected, but also induction of heme oxygenase (HO-1), a
      marker of oxidative damage, and lipid peroxidation. Hao1 mRNA levels were not
      altered significantly in livers of rats administered doses of iron sufficient to
      induce ferritin expression and to repress IRP activity, but not to activate HO-1
      and to promote lipid peroxidation, as well as in the liver of iron-deficient
      rats. These observations were not consistent with a post-transcriptional down
      regulation of Hao1 by iron through the IRE/IRP pathway and suggested an effect of
      reactive oxygen species (ROS). Indeed, a marked decrease of Hao1 mRNA was
      observed in the liver of rats subjected to oxidative stress induced by either
      glutathione depletion or postischemic reperfusion. Nuclear run-on analysis showed
      an effect of ROS at the transcriptional level. In conclusion, down-regulation of
      Hao1 expression during oxidative stress may provide a mechanism to prevent
      excessive H2O2 formation in liver peroxisomes and may represent the prototype of
      a poorly recognized but potentially relevant response to oxidative injury
      involving down-regulation of ROS-producing enzymes.

PMID- 14578853
TI  - Adenovirus-mediated expression of Cu/Zn- or Mn-superoxide dismutase protects
      against CYP2E1-dependent toxicity.
AB  - CYP2E1 induction by ethanol is one mechanism by which ethanol creates oxidative
      stress in the liver. The superoxide dismutases (SODs) are an important
      antioxidant enzyme defense system against reactive oxygen species (ROS). To
      investigate the protective role of SOD against CYP2E1-dependent toxicity, a
      transfected HepG2 cell line overexpressing CYP2E1 (E47 cells) was infected with
      adenoviral vectors containing Cu/Zn-SOD complementary DNA (cDNA) (Ad.SOD1) and Mn
      SOD cDNA (Ad.SOD2). Forty-eight hours after infection, intracellular levels and
      activity of Cu/Zn-SOD and Mn-SOD were increased about 2- and 3-fold,
      respectively. Localization of the overexpressed Cu/Zn-SOD in the cytosol and Mn
      SOD in the mitochondria was confirmed by assaying the levels and activity of SOD
      in the corresponding isolated fractions. Arachidonic acid (AA) plus iron-induced
      cell death was partially prevented in both Ad.SOD1- and Ad.SOD2-infected E47
      cells. Overexpression of Cu/Zn-SOD and Mn-SOD also partially protected E47 cells
      from the increase in reactive oxygen production and lipid peroxidation and the
      loss of mitochondrial membrane potential induced by AA and iron. Infection with
      Cu/Zn-SOD and Mn-SOD also protected the E47 cells against AA toxicity or
      buthionine sulfoximine (BSO)-dependent toxicity. CYP2E1 levels and catalytic
      activity were not altered by overexpression of Cu/Zn-SOD or Mn-SOD. Cu/Zn-SOD in
      the cytosol and Mn-SOD in mitochondria each are capable of protecting HepG2 cells
      expressing CYP2E1 against cytotoxicity induced by pro-oxidants. In conclusion,
      these enzymes may be useful in the prevention or improvement of liver injury
      produced by agents known to be metabolized by CYP2E1 to reactive intermediates
      and to cause oxidative stress.

PMID- 14578855
TI  - Membrane cholesterol but not putative receptors mediates anandamide-induced
      hepatocyte apoptosis.
AB  - The endogenous cannabinoid anandamide, a lipid mediator, induces various
      physiologic events such as vascular relaxation, inhibition of gap-junctions
      formation, tumor proliferation, neurologic analgesia, and apoptosis. Although
      increased concentration of anandamide in plasma has been implicated in
      pathophysiologic states including endotoxin-induced hypotension, the effects of
      anandamide on hepatocytes still remain unclear. In this study, we present
      evidence that plasma anandamide concentration is highly increased in severe
      hepatitis and cirrhosis patients. In addition, concentrations of anandamide
      within the pathophysiologic range potently induced apoptosis of hepatoma cell
      line (Hep G2) and primary hepatocytes, suggesting a possible link between
      increased anandamide level and hepatocyte damage. Anandamide-induced cell death
      was preceded by G0/G1 cell-cycle arrest, activation of proapoptotic signaling
      (i.e., p38 MAPK and JNK), and inhibition of antiapoptotic signaling (i.e.,
      PKB/Akt) pathways. Moreover, anandamide increased susceptibility to oxidative
      stress-induced hepatocyte damage. In this context, methyl-beta-cyclodextrin
      (MCD), a membrane cholesterol depletor, or mevastatin, an HMG-CoA reductase
      inhibitor, or N-acetyl cysteine, an antioxidant, potently inhibited the
      anandamide-induced proapoptotic events and cell death, whereas putative
      cannabinoid receptor antagonists did not exhibit an inhibitory effect on
      anandamide-induced cell death. Furthermore, binding assay using polymyxin beads
      revealed that anandamide could interact with cholesterol. In conclusion, our data
      suggest that cholesterol present in the cell membrane determines the fate of
      hepatocytes exposed to anandamide, possibly functioning as an anandamide
      receptor.

PMID- 14578856
TI  - Inhibition of proteasome function leads to NF-kappaB-independent IL-8 expression
      in human hepatocytes.
AB  - Breakdown of cellular proteins is a highly regulated process, and the ubiquitin
      proteasome pathway is the major proteolytic system in the cell. It regulates the
      levels of numerous proteins that control gene expression and cell division, as
      well as responses to stress and inflammation. Recent studies have reported
      abnormalities in proteasome function in alcoholic liver disease (ALD). Moreover,
      a direct relation has been reported between impaired proteasome function and
      oxidative stress in experimental models of ALD. Neutrophil infiltration is a
      hallmark of ALD, and activated neutrophils are thought to play a role in the
      pathology of ALD. As a potent neutrophil chemoattractant and activator,
      interleukin 8 (IL-8) likely plays a key mechanistic role in many forms of liver
      injury. In this study, we evaluated the effects of inhibition of proteasome
      function on expression and release of IL-8 by human fetal hepatocytes and
      hepatoma cells. Our data demonstrate that inhibition of proteasome function in
      hepatocytes leads to apoptotic cell death. Decreased hepatocyte survival
      coincides with enhanced expression of IL-8, both at the protein and the messenger
      RNA (mRNA) levels. This increase in IL-8 is independent of nuclear factor kappaB
      (NF-kappaB) activation and is associated with an increase in c-Jun N-terminal
      kinase (JNK) and activator protein-1 (AP-1) activity. In conclusion, hepatocytes
      dying because of inhibition of proteasome function produce massive quantities of
      the proinflammatory chemokine IL-8, possibly resulting in neutrophil
      infiltration, increased inflammation, and liver injury.

PMID- 14578857
TI  - Kupffer cell engulfment of apoptotic bodies stimulates death ligand and cytokine
      expression.
AB  - Hepatocyte apoptosis by death receptors, hepatic inflammation, and fibrosis are
      prominent features of liver diseases. However, the link between these processes
      remains unclear. Our aim was to ascertain whether engulfment of apoptotic bodies
      by Kupffer cells promotes hepatic inflammation and fibrosis. Isolated murine
      Kupffer cells efficiently engulfed apoptotic bodies generated from UV-treated
      mouse hepatocytes. Engulfment of the apoptotic bodies, but not latex beads,
      stimulated Kupffer cell generation of death ligands, including Fas ligand, and
      tumor necrosis factor alpha (TNF-alpha). Both apoptotic body phagocytosis and
      death ligand generation were attenuated by gadolinium chloride, a Kupffer cell
      toxicant. Kupffer cells isolated from 3-day bile duct-ligated (BDL) mice were
      phenotypically similar to apoptotic body-"fed" Kupffer cells with enhanced death
      ligand expression; inhibition of hepatocyte apoptosis with a caspase inhibitor
      prevented this Kupffer cell activation. Consistent with a role for Kupffer cells
      in liver inflammation and fibrosis, gadolinium chloride attenuated neutrophil
      infiltration and markers for stellate cell activation. In conclusion, these
      findings support a model of cholestatic liver injury where Kupffer cell
      engulfment of apoptotic bodies promotes inflammation and fibrogenesis.

PMID- 14578859
TI  - Systemic, renal, and hepatic hemodynamic derangement in cirrhotic patients with
      spontaneous bacterial peritonitis.
AB  - Spontaneous bacterial peritonitis (SBP) is frequently associated with renal
      failure. This study assessed if systemic and hepatic hemodynamics are also
      affected by this condition. Standard laboratory tests, tumor necrosis factor
      alpha (TNF-alpha) in plasma and ascitic fluid, plasma renin activity (PRA) and
      norepinephrine (NE), and systemic and hepatic hemodynamics were determined in 23
      patients with SBP at diagnosis and after resolution of infection. Eight patients
      developed renal failure during treatment. At diagnosis of infection, patients
      developing renal failure showed significantly higher values of TNF-alpha, blood
      urea nitrogen (BUN), PRA and NE, peripheral vascular resistance, and hepatic
      venous pressure gradient (HVPG) and lower cardiac output than patients not
      developing renal failure. During treatment, a significant reduction in cardiac
      output and arterial pressure and increase in PRA and NE, HVPG, and Child-Pugh
      score were observed in the first group but not in the second. Peripheral vascular
      resistance remained unmodified in both groups. Changes in PRA and NE correlated
      inversely with changes in arterial pressure and directly with changes in BUN,
      Child-Pugh score, and HVPG. Five patients in the renal failure group developed
      encephalopathy, and 6 died. In the group without renal failure, none of the
      patients developed encephalopathy or expired. In conclusion, patients with SBP
      frequently develop a rapidly progressive impairment in systemic hemodynamics,
      leading to severe renal and hepatic failure, aggravation of portal hypertension,
      encephalopathy, and death. This occurs despite rapid resolution of infection and
      is associated with an extremely poor prognosis.

PMID- 14578858
TI  - Intracellular accumulation of pIgA-R and regulators of transcytotic trafficking
      in cholestatic rat hepatocytes.
AB  - Bile duct ligation (BDL) impairs basolateral-to-apical transcytosis in
      hepatocytes, causing accumulation of transcytotic carriers for the polymeric IgA
      receptor (pIgA-R) and redistribution of secretory component (SC) from bile to
      blood. To gain insight into the mechanisms regulating transcytosis and the
      pathophysiology of cholestasis, we investigated nascent protein trafficking in
      control and BDL livers using cell fractionation in the context of in vivo pulse
      chase experiments and immunoblot analysis. Control and cholestatic hepatocytes
      trafficked [35S]-labeled serum proteins and the pIgA-R along the secretory
      pathway with identical kinetics. However, BDL impaired transcytosis, causing (1)
      accumulation of the pIgA-R, rab3D, rab11a, and other candidate regulators of
      apical-directed secretion in a crude vesicle carrier fraction (CVCF) enriched in
      transcytotic carriers; (2) slow delivery of [35S]-labeled SC to bile; and (3)
      paracellular reflux of SC from bile to blood. In conclusion, these data indicate
      that the secretory and transcytotic pathways remain polarized in cholestatic
      hepatocytes and suggest that the pIgA-R traffics through postendosomal rab3D-,
      rab11a-, and syntaxin 2-associated compartments, implicating these proteins in
      the regulation of transcytosis.

PMID- 14578860
TI  - Quantitative T1 mapping of hepatic encephalopathy using magnetic resonance
      imaging.
AB  - Changes are shown in the spin-lattice (T1) relaxation time caused by the putative
      deposition of manganese in various brain regions of hepatic encephalopathy (HE)
      patients using a novel and fast magnetic resonance imaging (MRI) method for
      quantitative relaxation time mapping. A new method, T1 mapping with partial
      inversion recovery (TAPIR), was used to obtain a series of T1-weighted images to
      produce T1 maps. Imaging of 15 control subjects and 11 patients was performed on
      a 1.5T MRI scanner. The measurement time per patient with this technique,
      including adjustments, was approximately 5 minutes. Regions of interest in the
      globus pallidus, the caudate nucleus, the posterior and anterior limbs of the
      internal capsule, the putamen, the frontal and occipital white matter, the white
      matter of the corona radiata, the occipital visual and frontal cortices, and the
      thalamus were interactively defined in the left hemisphere and analyzed with
      respect to their T1 values. T1 changes in the brains of HE patients can be
      determined quantitatively with TAPIR in short, clinically relevant measurement
      times. Significant correlations between the change in T1 and HE severity have
      been shown in the globus pallidus, the caudate nucleus, and the posterior limb of
      the internal capsule. No significant correlation of T1 with grade of HE was found
      in the putamen, frontal white matter, white matter of the corona radiata, white
      matter in the occipital lobe, the anterior limb of the internal capsule, visual
      cortex, thalamus, or frontal cortex. In conclusion, these measurements show that
      T1 mapping is feasible in short, clinically relevant acquisition times.

PMID- 14578861
TI  - Validity of the 13C-caffeine breath test as a noninvasive, quantitative test of
      liver function.
AB  - The properties of caffeine render it an ideal substrate for a quantitative test
      of liver function. The aim of this study was to determine whether the caffeine
      breath test (CBT) using orally administered 13C-caffeine correlates reliably with
      plasma caffeine clearance and reflects varying degrees of liver dysfunction. The
      CBT was performed in 25 healthy controls; 20 subjects with noncirrhotic, chronic
      hepatitis B or C; and 20 subjects with cirrhosis. Plasma caffeine clearance was
      assayed simultaneously with the CBT in a cohort of these subjects. Over a broad
      range of caffeine clearances, the CBT exhibited a highly significant correlation
      with plasma clearance (r = 0.85, P <.001). Cirrhotic patients were characterized
      by significantly reduced CBT values (1.15 +/- 0.75 delta per thousand mg(-1))
      compared with controls (2.23 +/- 0.76; P =.001) and hepatitic patients (1.83 +/-
      1.05; P =.04). There was a significant inverse relationship between the CBT and
      Child-Pugh score (r = -.74, P =.002). The intraclass correlation coefficient
      between repeated CBTs in 20 subjects with normal and cirrhotic livers was 0.89.
      Although smoking was associated with an 86% to 141% increase in CBT in all
      groups, the CBT was able to distinguish control, hepatitic, and cirrhotic smokers
      (5.36 +/- 0.82, 3.63 +/- 1.21, and 2.14 +/- 1.14, respectively, P =.001).
      Multivariate analysis revealed that only smoking (P <.001) and disease state (P
      =.001) were significant predictors of the CBT. In conclusion, the 13C-CBT
      represents a valid indicator of plasma caffeine clearance and correlates
      reproducibly with hepatic dysfunction.

PMID- 14578862
TI  - Adjuvant intra-arterial injection of iodine-131-labeled lipiodol after resection
      of hepatocellular carcinoma.
AB  - The high rate of recurrence after surgical resection of hepatocellular carcinoma
      (HCC) is a major therapeutic challenge. Postoperative injection of 131-iodine
      labeled lipiodol (131I-Lip) into the hepatic artery has been proposed as adjuvant
      treatment (Lau et al.). We analyzed 2 retrospective series of matched patients
      treated in our unit before and after addition of 131I-Lip adjuvant therapy to our
      standard surgical strategy. Thirty-eight patients who had undergone surgical
      resection of HCC after January 1999 were given adjuvant intra-arterial injection
      of 131I-Lip after surgery. These patients were matched with 38 other patients who
      had undergone surgical resection only between January 1997 and January 1999. The
      frequency of recurrences, disease-free rates, and overall survival rates were
      compared. The 2 groups were similar for clinical, biologic, or histologic
      parameters studied and Cancer Liver Italian Program scores. There were 15
      recurrences in the group without adjuvant treatment and 9 in the group with 131I
      Lip adjuvant treatment. The 1-, 2-, and 3-year disease-free survival rates (+/
      95% confidence interval) were different (P <.02): 94.7% +/- 3.6%, 83.7% +/- 6.1%,
      and 68.4% +/- 9.7%, respectively, in the 131I-Lip group versus 73.7% +/- 7.1%,
      54.3% +/- 8.2%, and 41.5% +/- 10.5% in the surgery group. The 1-, 2-, and 3-year
      survival rates (+/-95% confidence interval) also were different (P <.02): 94.7%
      +/- 3.6%, 91.7% +/- 4.6%, and 91.7% +/- 4.6%, respectively, in the 131I-Lip group
      versus 94.7% +/- 3.6%, 71.3% +/- 7.8%, and 49.9% +/- 10% in the surgery group. In
      conclusion, this retrospective analysis supports the promising contribution of
      postoperative injection of 131I-Lip after resection of HCC. A randomized study
      including more patients would be necessary to confirm its contribution to
      therapeutic management.

PMID- 14578863
TI  - PTK2 and EIF3S3 genes may be amplification targets at 8q23-q24 and are associated
      with large hepatocellular carcinomas.
AB  - We investigated 39 primary hepatocellular carcinomas (HCCs) for aberrations in
      DNA copy number, using comparative genomic hybridization (CGH). Gain of DNA at 8q
      was common in these tumors; high-level gains, indicative of gene amplification,
      occurred most frequently at 8q23-q24. Gains of 8q correlated with large (>5 cm)
      tumor size. To identify targets of the amplification events involving 8q, we
      determined expression levels of 14 candidate genes within that region in a total
      of 41 HCCs by means of real-time quantitative reverse-transcription polymerase
      chain reactions (RT-PCR). Significant correlation was found between elevated
      levels of expression and increases in copy number for PTK2 (located at 8q24.3)
      and EIF3S3 (at 8q23.3), but for none of the other candidates, which included MYC
      (8q24.1). Southern blot analyses confirmed that PTK2 and EIF3S3 were amplified,
      respectively, in 5 (19%) and 7 (26%) of the 27 tumors examined in accordance with
      expression patterns, an indication that expression of PTK2 and EIF3S3 was
      probably up-regulated by the amplification mechanism. When we analyzed potential
      relationships between elevated expression of PTK2 and EIF3S3 and
      clinicopathologic parameters, high expression of the 2 transcripts was
      significantly associated with large (>5 cm) tumor size and with hepatitis B virus
      (HBV) infection. In conclusion, PTK2 and EIF3S3, which, respectively, encode
      focal adhesion kinase and the p40 subunit of the eukaryotic initiation factor 3,
      were probable targets within the amplification at 8q23-q24 and may be involved in
      progression of HCC.

PMID- 14578864
TI  - Patients with primary biliary cirrhosis react against a ubiquitous xenobiotic
      metabolizing bacterium.
AB  - Infectious and environmental agents have been proposed as immunologic triggers
      for primary biliary cirrhosis (PBC). Recently, a ubiquitous organism that
      metabolizes organic compounds and estrogens, Novosphingobium aromaticivorans, has
      been defined. Importantly, 2 bacterial proteins have homology with the E2
      component of the pyruvate dehydrogenase complex (PDC-E2). Sera from 97 patients
      with PBC, 46 first-degree relatives, 10 spouses, and 195 controls were studied
      for reactivity against N. aromaticivorans and Escherichia coli. The reactivity
      was defined by absorption, affinity purification, and using monoclonal antibodies
      to PDC-E2. Stool samples from 20 patients with PBC and 34 controls were analyzed
      by polymerase chain reaction (PCR) for the presence of N. aromaticivorans. Sera
      from 100% of anti-PDC-E2 positive (77/77), 33% of anti-BCOADC E2 positive (1/3),
      and 12% of antimitochondrial antibody (AMA) negative patients with PBC (2/17)
      reacted with titers up to 10(-6) against two known lipoylated bacterial proteins
      (47 and 50 kd) from N. aromaticivorans, including patients with early disease.
      This titer was approximately 100- to 1,000-fold higher than against E. coli and
      verified by absorption, use of affinity-purified sera, and monoclonal antibody
      reagents. Moreover, 78 of 80 AMA-positive and 5 of 17 AMA-negative patients with
      PBC had antibodies against 3 other N. aromaticivorans proteins. In contrast, 0 of
      195 control sera reacted against N. aromaticivorans. Approximately 25% of
      patients and controls had N. aromaticivorans in their fecal specimens. In
      conclusion, based on protein homology, capacity to metabolize xenobiotics as well
      as modulate estrogens, its presence in feces, and specific immunologic response,
      we propose that N. aromaticivorans is a candidate for the induction of PBC.

PMID- 14578865
TI  - Hepatitis B virus X protein regulates transactivation activity and protein
      stability of the cancer-amplified transcription coactivator ASC-2.
AB  - Hepatitis B virus X protein (HBx) is a transcriptional coactivator that plays a
      significant role in the regulation of genes involved in inflammation and cell
      survival. A recently identified cellular coactivator, activating signal
      cointegrator 2 (ASC-2), is enriched in liver cancer cells and associates with
      many transcription factors that are active in hepatocytes. The tissue
      colocalization of these 2 proteins, in view of their similar regulatory
      functions, led us to examine whether HBx and ASC-2 cooperate in transcriptional
      activation of gene expression. Glutathione S-transferase (GST) pull-down assays
      and mammalian 2-hybrid analysis show that the transactivation domain of HBx
      interacts with the C-terminal domain of ASC-2. In fact, these 2 proteins
      associated in a ternary complex that included the transcriptional activator
      retinoid X receptor (RXR). Mechanistically, on expression of HBx, the half-life
      of the ASC-2 coactivator is observed to increase in concordance with the observed
      increase in ASC-2-dependent coactivation of transcription. In conclusion, these
      results show that HBx stabilizes the cellular coactivator ASC-2 through direct
      protein-protein interaction, affecting the regulation of genes actively
      transcribed in liver cancer cells.

PMID- 14578866
TI  - Determinants for sustained HBeAg response to lamivudine therapy.
AB  - There are inconsistent data on the durability of hepatitis B e antigen (HBeAg)
      seroconversion after lamivudine is discontinued. The aim of this study was to
      examine the determinants for sustained HBeAg response to lamivudine therapy. Both
      host and viral factors as well as the drug factor were compared between 43
      patients with sustained HBeAg response and 39 patients whose response was not
      sustained. All of them received a mean period of 16 months (range, 3-55 months)
      lamivudine therapy and had achieved complete response (HBeAg seroconversion plus
      HBV DNA seroclearance by hybrid capture assay and normal alanine aminotransferase
      [ALT]) and were followed-up for a mean period of 44 months (range, 12-88 months).
      Stepwise logistic regression model was used to estimate the sustained response on
      the presence of the following variables: age; gender; pretherapy ALT; total
      bilirubin and HBV DNA levels; time to HBeAg seroconversion; additional lamivudine
      treatment after HBeAg seroconversion; total duration of treatment; hepatitis
      activity index scores; periportal, intralobular, and portal inflammation and
      fibrosis scores; scores excluding fibrosis; status of precore mutation; basal
      core promoter mutation; and genotype. The results showed that genotype (OR,
      5.922; 95% CI, 1.611-21.768; P =.007), age (OR, 0.943; 95% CI, 0.891-0.997; P
      =.040), and additional treatment (OR, 1.097; 95% CI, 1.028-1.171; P =.005) were
      independent factors to sustained HBeAg response. Further categorical analysis
      disclosed that patients with genotype B, age < or =36 years, and additional
      lamivudine treatment over 8 months have higher sustained response. In conclusion,
      HBV genotype, age, and additional treatment are the major determinants for the
      sustained HBeAg response to lamivudine therapy.

PMID- 14578867
TI  - Deficiency in virion secretion and decreased stability of the hepatitis B virus
      immune escape mutant G145R.
AB  - Hepatitis B virus with a G145R mutation in the small surface protein is
      considered the quintessential immune escape mutant because it frequently is found
      in vaccinated individuals with breakthrough infections and liver transplant
      recipients under anti-hepatitis B surface antigen (HBsAg) immunoglobulin
      prophylaxis. Nowadays the prevalence of the variant progressively increases.
      However, because spread of a virus depends not only on immune pressure but also
      on the viral phenotype, we investigated the biologic properties of the G145R
      variant. The G145R mutation was introduced into wild-type (Wt) virus genome by in
      vitro mutagenesis. After transfection into human hepatoma cells, the DNA, RNA,
      and protein synthesis and viral secretion ability of the mutant were studied.
      Furthermore, cotransfection studies were performed with the G145R variant and a
      Wt virus S-protein expressing construct and vice versa. Production and stability
      of viral messenger RNAs (mRNAs), DNA, and proteins were not affected by the G145R
      mutation. In contrast, secretion of mutant virions was reduced significantly.
      Only 20% of virions were found in the medium of G145R variant-transfected cells
      compared with Wt virus. Furthermore, mutant virions were more sensitive to
      detergent treatment suggesting a diminished stability. In cotransfection studies,
      Wt virus S-protein rescued secretion of mutant virions, whereas mutant S-protein
      had a transdominant negative effect on secretion of Wt virus. Both mechanisms may
      support persistence of the defective mutant in a mixed population with Wt virus.
      In conclusion, the significant defect of the G145R mutant for secretion of
      infectious virions and the diminished stability of mutant virions may limit
      global spread of the mutant.

PMID- 14578868
TI  - Cyclosporin A suppresses replication of hepatitis C virus genome in cultured
      hepatocytes.
AB  - Persistent infection of hepatitis C virus (HCV) is a major cause of liver
      diseases such as chronic hepatitis, liver cirrhosis, and hepatocellular
      carcinoma. Searching for a substance with anti-HCV potential, we examined the
      effects of a variety of compounds on HCV replication using a HCV subgenomic
      replicon cell culture system. Consequently, the immunosuppressant cyclosporin A
      (CsA) was found to have a suppressive effect on the HCV replicon RNA level and
      HCV protein expression in these cells. CsA also inhibited multiplication of the
      HCV genome in a cultured human hepatocyte cell line infected with HCV using HCV
      positive plasma. This anti-HCV activity of CsA appeared to be independent of its
      immunosuppressive function. In conclusion, our results suggest that CsA may
      represent a new approach for the development of anti-HCV therapy.

PMID- 14578869
TI  - A pilot study of therapeutic vaccination with envelope protein E1 in 35 patients
      with chronic hepatitis C.
AB  - New treatments are needed for chronic hepatitis C patients in whom viral
      clearance cannot be achieved. Thirty-five chronic hepatitis C patients (genotype
      1) were randomized to receive 20 mug of recombinant HCV E1 (E1) (n = 26) or
      placebo (n = 9) intramuscularly at weeks 0, 4, 8, 12, and 24. Thirty-four then
      received open-label E1 vaccine at weeks 50, 53, 56, 59, 62, and 65. Twenty-four
      patients (12 men, 12 women; mean age, 52 y; 18 interferon-based treatment
      failures; mean baseline alanine aminotransferase [ALT] level, 118 IU/L) underwent
      a biopsy before and after 2 courses of E1, 17 months later. Liver histology was
      scored by 2 blinded pathologists according to the Ishak and Metavir systems.
      Postinjection reactions were similar to placebo (alum only). Nine of 24 patients
      (38%) had improvement of 2 points or more, 10 (41%) remained stable, and 5 (21%)
      showed worsening in total Ishak score. Nine patients (38%) improved both on Ishak
      and Metavir fibrosis scores. Plasma HCV-RNA levels remained unchanged, whereas
      ALT levels showed a trend toward a decrease during treatment. All but 3 patients
      developed a significant de novo E1-specific T-cell response. The increase in anti
      E1 antibody levels correlated with the decrease in total Ishak score and with the
      relative decreases in both Ishak fibrosis score and ALT level (all P < or =.01).
      In conclusion, E1 therapeutic vaccination is well tolerated and the observed
      effects warrant further study.

PMID- 14578872
TI  - Molecular assays for hepatitis B virus infection.

PMID- 14578870
TI  - Characterization of HCV-specific Patr class II restricted CD4+ T cell responses
      in an acutely infected chimpanzee.
AB  - Resolution of hepatitis C virus (HCV) infection is associated with strong and
      sustained virus-specific CD4+ T cell responses. In this study, we investigated
      the evolution of functional T cell responses during acute infection of a
      chimpanzee and the longevity of these lymphocytes in blood and liver after
      resolution of infection. Viremia increased through the first 3 weeks of infection
      and then remained stable until the onset of T cell responses at weeks 6 and 8
      postinfection. CD4+ T cells targeting nonstructural HCV proteins were detected in
      proliferation assays by week 6 postinfection, but they failed to produce
      interferon gamma (IFN-gamma). HCV-specific CD4+ and CD8+ T cells with the ability
      to produce IFN-gamma appeared at week 8 when a rapid 10-fold reduction in plasma
      viremia was first observed. This cytokine response persisted through to week 24
      when infection apparently resolved. T cell lines targeting 3 CD4+ T cell epitopes
      and 1 CD8+ T cell epitope were derived from liver and their Patr major
      histocompatibility complex (MHC) restriction elements were identified. In
      retrospective studies performed on cryopreserved peripheral blood mononuclear
      cells (PBMCs) collected at various timepoints after infection, the onset of an
      IFN-gamma response measured against the class II restricted epitopes correlated
      with viral clearance. In conclusion, the characterization of the HCV epitopes and
      MHC class II restriction elements described here will facilitate a detailed
      comparison of CD4+ T cell function in animals with resolved and persistent
      infections.

PMID- 14578873
TI  - Hepatitis B vaccination and anti-HBc-positive livers in children.

PMID- 14578874
TI  - Noninvasive diagnosis of fibrosis: the truth is rarely pure and never simple.

PMID- 14578875
TI  - CC531S-induced damage of the rat liver sinusoidal endothelial lining is mediated
      by the Fas/FasL pathway.

PMID- 14578876
TI  - Just a second.

PMID- 14578877
TI  - Atomic layer deposition of transition metals.
AB  - Atomic layer deposition (ALD) is a process for depositing highly uniform and
      conformal thin films by alternating exposures of a surface to vapours of two
      chemical reactants. ALD processes have been successfully demonstrated for many
      metal compounds, but for only very few pure metals. Here we demonstrate processes
      for the ALD of transition metals including copper, cobalt, iron and nickel.
      Homoleptic N,N'-dialkylacetamidinato metal compounds and molecular hydrogen gas
      were used as the reactants. Their surface reactions were found to be
      complementary and self-limiting, thus providing highly uniform thicknesses and
      conformal coating of long, narrow holes. We propose that these ALD layers grow by
      a hydrogenation mechanism that should also operate during the ALD of many other
      metals. The use of water vapour in place of hydrogen gas gives highly uniform,
      conformal films of metal oxides, including lanthanum oxide. These processes
      should permit the improved production of many devices for which the ALD process
      has previously not been applicable.

PMID- 14578878
TI  - A reversible copper extrusion-insertion electrode for rechargeable Li batteries.
AB  - Although widely used, the most promising Li-based technologies still suffer from
      a lack of suitable electrodes. There is therefore a need to seek new materials
      concepts to satisfy the increasing demands for energy storage worldwide. Here we
      report on a new layered electrode material, Cu(2.33)V(4)O(11), which shows a
      sustainable reversible capacity of 270 mA h g(-1) at a voltage of about 2.7 V,
      and electrochemically reacts with Li in an unusual and spectacular way. The
      reaction entails a reversible Li-driven displacement process leading to the
      growth and disappearance of Cu dendrites with a concomitant reversible
      decomposition and recrystallization of the initial electrode material. We show
      from structural considerations that the uniqueness of Cu(2.33)V(4)O(11) is rooted
      in the peculiar flexibility of the stacked [V(4)O(11)](n) layers, which is due to
      the presence of pivot oxygen atoms. Fully reversible displacement reactions could
      provide a new direction for developing an alternative class of higher energy
      density Li storage electrodes.

PMID- 14578879
TI  - Congruent melting of gallium nitride at 6 GPa and its application to single
      crystal growth.
AB  - The synthesis of large single crystals of GaN (gallium nitride) is a matter of
      great importance in optoelectronic devices for blue-light-emitting diodes and
      lasers. Although high-quality bulk single crystals of GaN suitable for substrates
      are desired, the standard method of cooling its stoichiometric melt has been
      unsuccessful for GaN because it decomposes into Ga and N(2) at high temperatures
      before its melting point. Here we report that applying high pressure completely
      prevents the decomposition and allows the stoichiometric melting of GaN. At
      pressures above 6.0 GPa, congruent melting of GaN occurred at about 2,220 degrees
      C, and decreasing the temperature allowed the GaN melt to crystallize to the
      original structure, which was confirmed by in situ X-ray diffraction. Single
      crystals of GaN were formed by cooling the melt slowly under high pressures and
      were recovered at ambient conditions.

PMID- 14578880
TI  - Self-assembly of functional nanostructures from ABC triblock copolymers.
AB  - The spontaneous formation of nanostructured materials by molecular self-assembly
      of block copolymers is an active area of research, driven both by its inherent
      beauty and by a wealth of potential technological applications. Thin films of
      block copolymers have attracted increasing interest, particularly in view of
      possible applications in nanotechnology. Although much of the work has
      concentrated on block copolymers consisting of two components, the insertion of a
      third block greatly enlarges the structural diversity and allows incorporation of
      additional chemical functionality. Here we describe a highly ordered hexagonally
      perforated lamella structure based on an ABC triblock copolymer thin film. By
      suitable choice of the three blocks a versatile structure is formed. The
      perforated lamella can serve as a lithographic mask, it can be chemically
      converted into an amphiphilic structure without losing its order, and after
      selective removal of one of its constituents it could be used as a responsive
      membrane. Intriguingly, the particular choice of the blocks ensures that the
      structure is formed irrespective of the chemical nature of the solid substrate.
      The experimental results are supported by mesoscale computer simulations.

PMID- 14578881
TI  - In vitro expansion of hematopoietic stem cells by recombinant TAT-HOXB4 protein.
AB  - Hematopoietic stem cells (HSCs) can self-renew extensively after transplantation.
      The conditions supporting their in vitro expansion are still being defined.
      Retroviral overexpression of the human homeobox B4 (HOXB4) gene in mouse bone
      marrow cells enables over 40-fold expansion of HSCs in vitro. To circumvent the
      requirement for retroviral infection, we used recombinant human TAT-HOXB4 protein
      carrying the protein transduction domain of the HIV transactivating protein (TAT)
      as a potential growth factor for stem cells. HSCs exposed to TAT-HOXB4 for 4 d
      expanded by about four- to sixfold and were 8-20 times more numerous than HSCs in
      control cultures, indicating that HSC expansion induced by TAT-HOXB4 was
      comparable to that induced by the human HOXB4 retrovirus during a similar period
      of observation. Our results also show that TAT-HOXB4-expanded HSC populations
      retain their normal in vivo potential for differentiation and long-term
      repopulation. It is thus feasible to exploit recombinant HOXB4 protein for rapid
      and significant ex vivo expansion of normal HSCs.

PMID- 14578882
TI  - Ex vivo expansion of human hematopoietic stem cells by direct delivery of the
      HOXB4 homeoprotein.
AB  - Expansion of human hematopoietic stem cells (HSCs) is a major challenge in
      cellular therapy, and currently relies on the use of recombinant cytokines or on
      gene transfer of transcription factors. Of these, the HOXB4 homeoprotein protein
      is of particular interests as it promotes the expansion of mouse HSCs without
      inducing the development of leukemia. To eliminate any deleterious effects that
      might be associated with stable HOXB4 gene transfer into human cells, we took
      advantage of the ability of HOX proteins to passively translocate through cell
      membranes. Here we show that when cultured on stromal cells genetically
      engineered to secrete HOXB4, human long-term culture-initiating cells (LTC-ICs)
      and nonobese diabetic-severe combined immunodeficiency (NOD-SCID) mouse
      repopulating cells (SRCs) were expanded by more than 20- and 2.5-fold,
      respectively, over their input numbers. This expansion was associated with
      enhanced stem cell repopulating capacity in vivo and maintenance of
      pluripotentiality. This method provides a basis for developing cell therapy
      strategies using expanded HSCs that are not genetically modified.

PMID- 14578883
TI  - Mechanism of CD1d-restricted natural killer T cell activation during microbial
      infection.
AB  - CD1d-restricted natural killer T (NKT) cells are important for host defense
      against a variety of microbial pathogens. How and when these T cells become
      activated physiologically during infection remains unknown. Our data support a
      model in which NKT cells use a unique activation mechanism not requiring their
      recognition of microbial antigens. Instead, weak responses to CD1d-presented self
      antigens were amplified by interleukin 12 made by dendritic cells in response to
      microbial products, resulting in potent interferon-gamma secretion. NKT cells
      were among the first lymphocytes to respond during Salmonella typhimurium
      infection, and their activation in vivo also depended on interleukin 12 and CD1d
      recognition. We propose this mechanism of activation as a major pathway
      responsible for the rapid activation of NKT cells in different microbial
      infections.

PMID- 14578884
TI  - Modulation of tryptophan catabolism by regulatory T cells.
AB  - Regulatory T (T(R)) cells manifest constitutive expression of cytotoxic T
      lymphocyte-associated antigen 4 (CTLA-4), but the function of CTLA-4 in mediating
      the regulatory function of T(R) cells is unclear. We show here that mouse
      CD4+CD25+ cells, either resting or induced to overexpress CTLA-4 by treatment
      with antibody to CD3, initiated tryptophan catabolism in dendritic cells through
      a CTLA-4-dependent mechanism. This process required B7 expression and cytokine
      production by the dendritic cells. In contrast, T(R) cells cultured in the
      presence of bacterial lipopolysaccharide induced tryptophan catabolism by
      dendritic cells in a CTLA-4-independent but cytokine-dependent way. Thus,
      regulation of immunosuppressive tryptophan catabolism in dendritic cells might
      represent a major mechanism of action of T(R) cells.

PMID- 14578885
TI  - Interaction of reelin signaling and Lis1 in brain development.
AB  - Loss-of-function mutations in RELN (encoding reelin) or PAFAH1B1 (encoding LIS1)
      cause lissencephaly, a human neuronal migration disorder. In the mouse,
      homozygous mutations in Reln result in the reeler phenotype, characterized by
      ataxia and disrupted cortical layers. Pafah1b1(+/-) mice have hippocampal
      layering defects, whereas homozygous mutants are embryonic lethal. Reln encodes
      an extracellular protein that regulates layer formation by interacting with VLDLR
      and ApoER2 (Lrp8) receptors, thereby phosphorylating the Dab1 signaling molecule.
      Lis1 associates with microtubules and modulates neuronal migration. We
      investigated interactions between the reelin signaling pathway and Lis1 in brain
      development. Compound mutant mice with disruptions in the Reln pathway and
      heterozygous Pafah1b1 mutations had a higher incidence of hydrocephalus and
      enhanced cortical and hippocampal layering defects. Dab1 and Lis1 bound in a
      reelin-induced phosphorylation-dependent manner. These data indicate genetic and
      biochemical interaction between the reelin signaling pathway and Lis1.

PMID- 14578886
TI  - Human Alu element retrotransposition induced by genotoxic stress.
AB  - Alu elements are found exclusively in primate species and comprise over 10% of
      the human genome. To better define the mechanisms responsible for Alu
      replication, we introduced a human Alu element into mouse cells. We report that
      Alu retrotransposition can be induced in mouse cells by exposure to the
      topoisomerase II inhibitor etoposide and is mediated in trans by endogenous mouse
      long interspersed elements (LINEs).

PMID- 14578887
TI  - Spreading the word. A User's Guide to the Human Genome.

PMID- 14578888
TI  - Power to the people. A User's Guide to the Human Genome. Foreward.

PMID- 14578891
TI  - A User's Guide to the Human Genome. Introduction: putting it together.

PMID- 14578889
TI  - Genomic empowerment: the importance of public databases.

PMID- 14578892
TI  - A User's Guide to the Human Genome. Question 1. How does one find a gene of
      interest and determine that gene's structure? Once the gene has been located on
      the map, how does one easily examine other genes in that same region?

PMID- 14578893
TI  - A User's Guide to the Human Genome. Question 2. How can sequence-tagged sites
      within a DNA sequence be identified?

PMID- 14578894
TI  - A User's Guide to the Human Genome. Question 3. During a positional cloning
      project aimed at finding a human disease gene, linkage data have been obtained
      suggesting that the gene of interest lies between two sequence-tagged site
      markers. How can all the known and predicted candidate genes in this interval be
      identified? What BAC clones cover that particular region?

PMID- 14578895
TI  - A User's Guide to the Human Genome. Question 4. A user wishes to find all the
      single nucleotide polymorphisms that lie between two sequence-tagged sites. Do
      any of these single nucleotide polymorphisms fall within the coding region of a
      gene? Where can any additional information about the function of these genes be
      found?

PMID- 14578896
TI  - A User's Guide to the Human Genome. Question 5. Given a fragment of mRNA
      sequence, how would one find where that piece of DNA mapped in the human genome?
      Once its position has been determined, how would one find alternatively-spliced
      transcripts?

PMID- 14578898
TI  - A User's Guide to the Human Genome. Question 7. How would an investigator easily
      find compiled information describing the structure of a gene of interest? Is it
      possible to obtain the sequence of any putative promoter regions?

PMID- 14578897
TI  - A User's Guide to the Human Genome. Question 6. How would one retrieve the
      sequence of a gene, along with all annotated exons and introns, as well as a
      certain number of flanking bases for use in primer design?

PMID- 14578899
TI  - A User's Guide to the Human Genome. Question 8. How can one find all the members
      of a human gene family?

PMID- 14578900
TI  - A User's Guide to the Human Genome. Question 9. Are there ways to customize
      displays and designate preferences? Can tracks or features be added to displays
      by users on the basis of their own research?

PMID- 14578901
TI  - A User's Guide to the Human Genome. Question 10. For a given protein, how can one
      determine whether it contains any functional domains of interest? What other
      proteins contain the same functional domains as this protein? How can one
      determine whether there is a similarity to other proteins, not only at the
      sequence level, but also at the structural level?

PMID- 14578902
TI  - A User's Guide to the Human Genome. Question 11. An investigator has identified
      and cloned a human gene, but no corresponding mouse ortholog has yet been
      identified. How can a mouse genomic sequence with similarity to the human gene
      sequence be retrieved?

PMID- 14578903
TI  - A User's Guide to the Human Genome. Question 12. How does a user find
      characterized mouse mutants corresponding to human genes?

PMID- 14578904
TI  - A User's Guide to the Human Genome. Question 13. A user has identified an
      interesting phenotype in a mouse model and has been able to narrow down the
      critical region for the responsible gene to approximately 0.5 cM. How does one
      find the mouse genes in this region?

PMID- 14578905
TI  - A User's Guide to the Human Genome. Commentary: keeping biology in mind.

PMID- 14578908
TI  - The large Maf factor Traffic Jam controls gonad morphogenesis in Drosophila.
AB  - Interactions between somatic and germline cells are critical for the normal
      development of egg and sperm. Here we show that the gene traffic jam (tj)
      produces a soma-specific factor that controls gonad morphogenesis and is required
      for female and male fertility. tj encodes the only large Maf factor in Drosophila
      melanogaster, an orthologue of the atypical basic Leu zipper transcription
      factors c-Maf and MafB/Kreisler in vertebrates. Expression of tj occurs in
      somatic gonadal cells that are in direct contact with germline cells throughout
      development. In tj mutant gonads, somatic cells fail to inter-mingle and properly
      envelop germline cells, causing an early block in germ cell differentiation. In
      addition, tj mutant somatic cells show an increase in the level of expression for
      several adhesion molecules. We propose that tj is a critical modulator of the
      adhesive properties of somatic cells, facilitating germline-soma interactions
      that are essential for germ cell differentiation.

PMID- 14578909
TI  - Load-dependent kinetics of force production by smooth muscle myosin measured with
      optical tweezers.
AB  - Muscle contraction is driven by the cyclical interaction of myosin with actin,
      coupled with ATP hydrolysis. Myosin attaches to actin, forming a crossbridge that
      produces force and movement as it tilts or rocks into subsequent bound states
      before finally detaching. It has been hypothesized that the kinetics of one or
      more of these mechanical transitions are dependent on load, allowing muscle to
      shorten quickly under low load, but to sustain tension economically, with slowly
      cycling crossbridges under high load conditions. The idea that muscle
      biochemistry depends on mechanical output is termed the 'Fenn effect'. However,
      the molecular details of how load affects the kinetics of a single crossbridge
      are unknown. Here, we describe a new technique based on optical tweezers to
      rapidly apply force to a single smooth muscle myosin crossbridge. The crossbridge
      produced movement in two phases that contribute 4 nm + 2 nm of displacement.
      Duration of the first phase depended in an exponential manner on the amplitude of
      applied load. Duration of the second phase was much less affected by load, but
      was significantly shorter at high ATP concentration. The effect of load on the
      lifetime of the bound crossbridge is to prolong binding when load is high, but to
      accelerate release when load is low or negative.

PMID- 14578910
TI  - Radiation-mediated proteolysis of CDT1 by CUL4-ROC1 and CSN complexes constitutes
      a new checkpoint.
AB  - Genomic integrity is maintained by checkpoints that guard against undesired
      replication after DNA damage. Here, we show that CDT1, a licensing factor of the
      pre-replication complex (preRC), is rapidly proteolysed after UV- or gamma
      irradiation. The preRC assembles on replication origins at the end of mitosis and
      during G1 to license DNA for replication in S phase. Once the origin recognition
      complex (ORC) binds to origins, CDC6 and CDT1 associate with ORC and promote
      loading of the MCM2-7 proteins onto chromatin, generating the preRC. We show that
      radiation-mediated CDT1 proteolysis is independent of ATM and CHK2 and can occur
      in G1-phase cells. Loss of the COP9-signalosome (CSN) or CUL4-ROC1 complexes
      completely suppresses CDT1 proteolysis. CDT1 is specifically polyubiquitinated by
      CUL4 complexes and the interaction between CDT1 and CUL4 is regulated in part by
      gamma-irradiation. Our study reveals an evolutionarily conserved and
      uncharacterized G1 checkpoint that induces CDT1 proteolysis by the CUL4-ROC1
      ubiquitin E3 ligase and CSN complexes in response to DNA damage.

PMID- 14578911
TI  - An NS3 protease inhibitor with antiviral effects in humans infected with
      hepatitis C virus.
AB  - Hepatitis C virus (HCV) infection is a serious cause of chronic liver disease
      worldwide with more than 170 million infected individuals at risk of developing
      significant morbidity and mortality. Current interferon-based therapies are
      suboptimal especially in patients infected with HCV genotype 1, and they are
      poorly tolerated, highlighting the unmet medical need for new therapeutics. The
      HCV-encoded NS3 protease is essential for viral replication and has long been
      considered an attractive target for therapeutic intervention in HCV-infected
      patients. Here we identify a class of specific and potent NS3 protease inhibitors
      and report the evaluation of BILN 2061, a small molecule inhibitor biologically
      available through oral ingestion and the first of its class in human trials.
      Administration of BILN 2061 to patients infected with HCV genotype 1 for 2 days
      resulted in an impressive reduction of HCV RNA plasma levels, and established
      proof-of-concept in humans for an HCV NS3 protease inhibitor. Our results further
      illustrate the potential of the viral-enzyme-targeted drug discovery approach for
      the development of new HCV therapeutics.

PMID- 14578912
TI  - Virology: fresh assault on hepatitis C.

PMID- 14578913
TI  - More evidence on blocking the renin-angiotensin-aldosterone system in
      cardiovascular disease and the long-term treatment of hypertension: data from
      recent clinical trials (CHARM, EUROPA, ValHEFT, HOPE-TOO and SYST-EUR2).

PMID- 14578914
TI  - Trends and social factors in blood pressure control in Scottish MONICA surveys
      1986-1995: the rule of halves revisited.
AB  - Time trends and social factors in detection, treatment and control of
      hypertension in the community were examined in four independent Scottish MONICA
      cross-sectional surveys in 1986, 1989, 1992 and 1995. Residents aged 25-64 years
      were recruited randomly from general practice lists in north Glasgow, Scotland
      with stratification by sex and 10-year age groups. A total of 1262 participated
      in the first survey, 1397 in the second, 1516 in the third and 1836 in the
      fourth. Differences and trends in proportions of hypertension undetected,
      detected but untreated, treated but uncontrolled and controlled across the four
      surveys were tested by chi(2), and the associations of the poor control of
      hypertension with social factors were estimated by multivariate logistic
      regression model to derive odds ratios. Using the cut point of >/=160/95 mmHg,
      proportion of hypertension undetected across the four surveys was 56.3, 44.6,
      32.0 and 38.2%, and of treated controlled hypertension was 15.2, 26.4, 32.0 and
      32.8% (both trends P<0.001). Multivariate analysis showed that poor control of
      hypertension was not related to social deprivation, but significantly related to
      being male, young, of low body mass index and heavy alcohol drinking. Undetected
      hypertension was significantly related to full-time employment, and untreated
      hypertension to high social class and possibly education level. These findings
      suggest that in this part of Scotland the management of hypertension has
      improved, so the 'rule of halves' no longer applies. Control of blood pressure is
      not positively associated with social deprivation, but people at a high risk of
      poor control of hypertension should be targeted.

PMID- 14578915
TI  - Blood pressure levels in 7 to 14-year-old Belgrade children.
AB  - The objective of the work was to study blood pressure and some anthropometric
      characteristics in children. The study design included the prevalence study at
      Belgrade, Serbia and Montenegro. The study comprised 1651 subjects (809 boys and
      842 girls) aged 7-14 years, that is, 2.6% of all relevant population. The average
      levels of systolic and diastolic blood pressures (SBP and DBP) were 113.4/70.3
      mmHg in boys and 114.6/71.1 mmHg in girls. High SBP was present in 4.7% of boys
      and in 5.3% of girls. High DBP was found in 5.6% of boys and in 4.8% of girls.
      According to multivariate regression analysis, in boys SBP and DBP were
      significantly associated with age, body mass index (BMI) and subscapular
      skinfold, SBP was also associated with body weight, and DBP with triceps
      skinfold. In girls, SBP was significantly related to BMI, suprailiac skinfold and
      body height, and DBP was significantly associated with BMI, suprailiac and
      subscapular skinfolds. The results of the present study support the opinion that
      BMI is a significant predictor of blood pressure in children and point out to
      suprailiac skinfold in girls as a possible predictor of blood pressure.

PMID- 14578916
TI  - Aggressive blood pressure control in general practice (ABC-GP) study: can the new
      targets be reached?
AB  - Based on outcome trials, guidelines for hypertension management recommend lower
      blood pressure (BP) goals using an individualized treatment strategy (IND) and
      referral to a specialist of patients uncontrolled after 6 months of treatment.
      This study aimed to evaluate the performance of General Practitioners (GPs) in
      reaching the recommended BP goals using the IND, or a stepwise treatment strategy
      (STEP) as used in the outcome trials. Trained GPs were randomized to reach the BP
      goals within 6 months using the IND or a STEP strategy in untreated or treated
      uncontrolled hypertensives. In all, 24 GPs recruited 528 patients of whom 443
      were analysed (mean age 65+/-9 years, 42% men, 70% treated, STEP/IND 12/12 GPs,
      231/211 patients). After 6 months, 83% of the patients had reached the diastolic
      BP goal, whereas only 51% the systolic (P<0.0001 for difference). Factors
      associated with uncontrolled systolic BP were diabetes, age >60 years and triple
      antihypertensive therapy at baseline. A faster BP reduction was achieved during
      the first 3 months using the STEP strategy, but at the cost of using more drugs
      (combination therapy in 68/59% for STEP/IND, P=0.06). At 6 months similar rates
      of control were achieved with the two strategies. In conclusion, in primary care
      the diastolic BP goal can be reached within 6 months in the majority of patients,
      whereas systolic BP remains uncontrolled in 50% of the cases. The IND should be
      the recommended treatment strategy, but further investigation is required on the
      reasons for treatment failure and the optimal strategy for its improvement.

PMID- 14578917
TI  - Changes in body weight and onset of hypertension in perimenopausal women.
AB  - We assessed the determinants of onset of hypertension in a large, prospective
      population-based study of perimenopausal women from the Kuopio Osteoporosis Risk
      Factor and Prevention (OSTPRE) study. The data collection started in 1989, when a
      baseline postal inquiry was sent to all women aged 47-56 years (n=14 220)
      residing in the Kuopio Province in Eastern Finland. Names, social security
      numbers and addresses were obtained from the Population Register Centre of
      Finland. A total of 11 798 women responded at baseline and at 5-year follow-up in
      1994. After the exclusion of 1777 women with prevalent hypertension at baseline
      and women with missing height or weight information, the study population
      consisted of 9485 without established hypertension at baseline. New cases of
      established hypertension during the follow-up (n=908) were ascertained with the
      Registry of Specially Refunded Drugs of the Finnish Social Insurance Institution
      (SII). According to the National Health Insurance, the SII granted 90%
      reimbursement for drug costs in defined chronic illnesses necessitating
      continuous medication, like arterial hypertension. Weight and weight gain both
      raised the risk by 5% per kg (P<0.001). Weight gain of 4-6 kg increased the risk
      of hypertension 1.25 times and a gain of more than 7 kg 1.65 times compared with
      the control (zero) group. To conclude, the onset of hypertension in peri- and
      early postmenopausal women was related to an increase in body weight despite
      controlling for initial body weight, reported physical activity and use of HRT.
      Therefore, preventing weight gain by dietary means and exercise is of great
      importance at menopausal age.

PMID- 14578918
TI  - Influence of losartan and atenolol on memory function in very elderly
      hypertensive patients.
AB  - The aim of this study was to compare the effect of the beta-adrenergic blocker
      atenolol and the Angiotensin II type 1 (AT1) receptor antagonist losartan on
      cognitive function in very elderly hypertensive patients. A total of 120 mild to
      moderate essential hypertensive (DBP >90 and <105 mmHg) patients, aged 75-89
      years, were studied. After a 4-week wash-out period on placebo, they were
      randomized to receive atenolol 50 mg or losartan 50 mg for 24 weeks according to
      a parallel arm design. At the end of the placebo period and of each active
      treatment period, BP was measured (by mercury sphygmomanometer, Korotkoff I and
      V) and cognitive function was evaluated through three different tests (word list
      memory, word list recall and word list fluency). Both atenolol and losartan were
      equally effective in reducing SBP (-22.1 and -23.1 mmHg, respectively, P< 0.01 vs
      baseline) and DBP (-10.3 and -11.2 mmHg, respectively, P< 0.01 vs baseline).
      Atenolol treatment did not induce significant changes in any test score, whereas
      losartan significantly increased the score of both the word list memory (+2.2,
      P<0.05 vs baseline) and the word list recall test (+2.1, P<0.05 vs baseline). The
      comparison between losartan and atenolol was significant (P<0.05) for both memory
      tests. These data suggest that in very elderly hypertensive patients, chronic AT1
      receptor blockade by losartan could improve cognitive function, in particular
      immediate and delayed memory.

PMID- 14578919
TI  - Headache is not more frequent among patients with moderate to severe
      hypertension.
AB  - The association between hypertension and headache has been a contentious issue.
      Most studies have showed that mild hypertension and headache are not associated,
      but this may not be the case in patients with hypertension classified at more
      severe stages. We investigated the association between hypertension classified at
      moderate to severe stages and headache in a cross-sectional study conducted in
      the hypertension clinic of a tertiary care University hospital. In total, 1763
      referred patients with a medical diagnosis of hypertension in most cases (95.7%)
      were evaluated by an extensive protocol questionnaire, detailed physical
      examination, laboratory examination, and had their blood pressure classified
      according to the VI Joint National Committee (JNC-VI) recommendation. Logistic
      regression models were used to explore the association between severity of
      hypertension and pulse pressure with the presence of headache, controlling for
      several potential confounders. The complaint of headache was referred by 903
      (51.3% of whole sample), and a total of 378 patients (21.4%) were classified at
      the moderate to severe stage (stage III of the JNC-VI report). The diagnosis of
      moderate to severe hypertension was not associated with the complaint of headache
      (OR 1.02, 95% CI from 0.79 to 1.30). Pulse pressure and headache were inversely
      associated (OR 0.91, 95% CI from 0.86 to 0.97, for 10 mmHg). We concluded that
      headache and hypertension classified at moderate to severe stages were not
      associated in patients attending to a hypertension clinic. The novel finding of
      an inverse association between pulse pressure and headache should be addressed in
      further investigations.

PMID- 14578920
TI  - Evaluation of the antioxidant response in the plasma of healthy or hypertensive
      subjects after short-term exercise.
AB  - Reactive oxygen species are produced during exercise. The antioxidants prevent or
      limit tissue damages by these species in physiological conditions. In particular,
      ascorbate and urate scavenge peroxynitrite, which can alter the function of many
      molecules, including the lecithin-cholesterol acyltransferase (LCAT) enzyme
      involved in reverse cholesterol transport. The aims of the present study were to
      compare the plasma antioxidant response to an ergometric test (ET) in
      hypertensive and healthy subjects, evaluate the exercise-dependent nitrosative
      stress in plasma, and assess whether the LCAT activity is altered by the
      exercise. Plasma samples, prepared before and after ET from hypertensive or
      healthy volunteers, were analysed for their levels of ascorbate, urate, alpha
      tocopherol, retinol, nitrotyrosine, and LCAT activity. The alpha-tocopherol and
      retinol levels did not significantly change in both groups during exercise, while
      the ascorbate level changed displaying higher increase in controls (+38.8%) than
      in hypertensives (+17.2%). In these patients, during ET, the urate and
      nitrotyrosine levels changed more than in normotensives (+13.5 and +40.6% vs -3.1
      and +25.2%, respectively). The antioxidants effectively prevented loss or
      reduction of LCAT activity, as it was similar in hypertensives and normotensives,
      and did not change after ET. The results demonstrate that exercise is associated
      with enhanced protein nitrosation, and suggest that the ascorbate or urate levels
      increase to limit oxidative damage.

PMID- 14578921
TI  - Lercanidipine vs lacidipine in isolated systolic hypertension.
AB  - This randomised, double-blind, double-dummy, parallel group, multicentre study
      compared the efficacy and tolerability of lercanidipine with lacidipine. Elderly
      patients with isolated systolic hypertension (supine blood pressure >/=160/<95
      mmHg) were enrolled and underwent a placebo run-in period of 14-27 days before
      random allocation to lercanidipine tablets 10 mg once daily (n=111) or lacidipine
      tablets 2 mg once daily (n=111) for the assessment period (112-160 days).
      Titration to lercanidipine 20 mg once daily (two 10 mg tablets) or lacidipine 4
      mg once daily (two 2 mg tablets) was allowed after 8 weeks, if required. Both
      treatments decreased supine and standing systolic and diastolic blood pressure
      between the end of the run-in period and the end of the assessment period
      (P<0.0001). At the end of the assessment period, the estimated mean treatment
      difference (95% confidence intervals) in supine systolic blood pressure was -0.81
      (-4.45, 2.84) mmHg. These confidence intervals were within the limits specified
      for equivalence, that is, (-5, 5) mmHg. Ambulatory blood pressure monitoring
      showed that the antihypertensive effects of both drugs lasted for the full 24-h
      dosing period and followed a circadian pattern. Both treatments were well
      tolerated with a low incidence of adverse drug reactions and a low withdrawal
      rate. Significantly fewer patients withdrew from treatment with lercanidipine
      (P=0.015). Neither treatment had any clinically significant effect on pulse rate
      or cardiac conduction. In conclusion, both treatments were equally effective in
      controlling supine systolic blood pressure in patients with isolated systolic
      hypertension.

PMID- 14578923
TI  - Regulation of protein phosphatases in disease and behaviour.

PMID- 14578922
TI  - Basolateral targeting by leucine-rich repeat domains in epithelial cells.
AB  - The asymmetric distribution of proteins to basolateral and apical membranes is an
      important feature of epithelial cell polarity. To investigate how basolateral LAP
      proteins (LRR (for leucine-rich repeats) and PDZ (for PSD-95/Discs-large/ZO-1),
      which play key roles in cell polarity, reach their target membrane, we carried
      out a structure-function study of three LAP proteins: Caenorhabditis elegans LET
      413, human Erbin and human Scribble (hScrib). Deletion and point mutation
      analyses establish that their LRR domain is crucial for basolateral membrane
      targeting. This property is specific to the LRR domain of LAP proteins, as the
      non-LAP protein SUR-8 does not localize at the basolateral membrane of epithelial
      cells, despite having a closely related LRR domain. Importantly, functional
      studies of LET-413 in C. elegans show that although its PDZ domain is dispensable
      during embryogenesis, its LRR domain is essential. Our data establish a novel
      paradigm for protein localization by showing that a subset of LRR domains direct
      subcellular localization in polarized cells.

PMID- 14578924
TI  - Dual targeting and function of a protease in mitochondria and chloroplasts.
AB  - Here we show, using the green fluorescent protein (GFP) fusion system, that an
      Arabidopsis thaliana zinc-metalloprotease (AtZn-MP) is targeted to both
      mitochondria and chloroplasts. A deletion mutant lacking the amino-terminal 28
      residues, with translation initiation at the second methionine residue, was
      imported into chloroplasts only. However, a mutated form of the full-length
      targeting peptide, in which the second methionine residue is changed to leucine,
      was imported to both organelles. No GFP fluorescence was detected when a frame
      shift mutation was introduced between the first and second ATG codons of the Zn
      MP-GFP construct, suggesting no alternative translational initiation. Our results
      show that the dual targeting of the Zn-MP is due to an ambiguous targeting
      peptide. Furthermore, we show that the recombinant AtZn-MP degrades mitochondrial
      and chloroplastic targeting peptides, indicating its function as a signal peptide
      degrading protease in both mitochondria and chloroplasts.

PMID- 14578925
TI  - Keeping hopes high.

PMID- 14578926
TI  - Prognostic value of C-reactive protein and cytokine assays for transplant-related
      mortality.

PMID- 14578928
TI  - Molecular remission of CML after autotransplantation followed by adoptive
      transfer of costimulated autologous T cells.
AB  - Four patients with chronic myelogenous leukemia (CML) that was refractory to
      interferon alpha (two patients) or imatinib mesylate (two patients), and who
      lacked donors for allogeneic stem cell transplantation, received autotransplants
      followed by infusions of ex vivo costimulated autologous T cells. At day +30
      (about 14 days after T-cell infusion), the mean CD4+ cell count was 481
      cells/microl (range 270-834) and the mean CD8+ count was 516 cells/microl (range
      173-1261). One patient had a relative lymphocytosis at 3.5 months after T-cell
      infusion, with CD4 and CD8 levels of 750 and 1985 cells/microl, respectively. All
      the four patients had complete cytogenetic remissions early after
      transplantation, three of whom also became PCR negative for the bcr/abl fusion
      mRNA. One patient, who had experienced progressive CML while on interferon alpha
      therapy, became PCR- post transplant, and remained in a molecular CR at 3.0 years
      of follow-up. All the four patients survived at 6, 9, 40, and 44 months post
      transplant; the patient who remained PCR+ had a cytogenetic and hematologic
      relapse of CML, but entered a molecular remission on imatinib.
      Autotransplantation followed by costimulated autologous T cells is feasible for
      patients with chronic phase CML, who lack allogeneic donors and can be associated
      with molecular remissions.

PMID- 14578929
TI  - Adenoviral infection in hematopoietic stem cell transplantation: early diagnosis
      with quantitative detection of the viral genome in serum and urine.
AB  - Early diagnosis and prompt introduction of effective therapy are imperative to
      manage systemic, often fatal adenoviral (AdV) disease following hematopoietic
      stem cell transplantation (SCT). We evaluated the usefulness of real-time
      polymerase chain reaction (PCR) in the diagnosis of AdV disease in SCT
      recipients. Seven SCT recipients, including three with AdV disease, were
      retrospectively evaluated for AdV genome detection. In serum specimens, the AdV
      genome was detected at >10(3) copies/ml in the pre-SCT period in two of the five
      recipients studied. These two patients subsequently developed AdV disease. The
      three patients with AdV disease had high levels of >10(5) copies/ml during the 4
      6 weeks post-SCT period. In none of these patients was the AdV genome detected in
      urine specimens in pre-SCT period. However, three recipients with detectable
      urinary levels during the period 1-2 weeks post-SCT subsequently developed AdV
      disease. Regarding the outcome, two of the three patients with AdV disease died
      of progressive renal failure. Our results suggest that quantitative determination
      of the AdV genome in serum and urine is useful to identify patients at high risk
      of developing AdV disease. Prospectively applied, these measures are expected to
      improve the dismal outcome of AdV disease in SCT recipients.

PMID- 14578931
TI  - Donor leukocyte infusion for late graft failure in a patient with severe aplastic
      anemia after allogeneic bone marrow transplantation.

PMID- 14578930
TI  - Addition of low-dose busulfan to cyclophosphamide in aplastic anemia patients
      prior to allogeneic bone marrow transplantation to reduce rejection.
AB  - Busulfan was added at the dose of 4 mg/kg to 200 mg/kg cyclophosphamide in 81
      patients (3-53 years, median 24) with aplastic anemia to reduce graft rejection.
      Graft-versus-host disease (GVHD) prophylaxis comprised cyclosporine-methotrexate.
      The number of prior transfusions was 0-276 (median 26), and 48% had received
      prior immunosuppressive therapy. Two patients experienced primary graft failure,
      and 10 secondary rejection at 28-1001 days (median 317 days). The cumulative
      incidence of rejection was 22%; for heavily transfused patients (>/=50 U) it was
      43% compared to 16% for the rest (P=0.06). Overall survival rate at 8 years was
      56%; patients who received </=15 and >15 transfusions was 78 and 50%,
      respectively (P=0.01), whereas it was 67 and 28% for </=50 and >50 transfusions,
      respectively (P=0.002). In multivariate analysis, higher number of prior
      transfusions, shorter period of immunosuppression with cyclosporine and GVHD were
      associated with inferior survival; moreover, a higher risk of graft rejection
      were associated with a higher number of prior transfusions and a trend was
      observed for a shorter cyclosporine administration. Low-dose busulfan is feasible
      and may be helpful in patients exposed to <50 transfusions. However, rejection
      remains a significant problem, mainly in heavily transfused patients.

PMID- 14578932
TI  - Allogeneic stem cell transplantation in patients with Fanconi's anemia and
      myelodysplasia or leukemia utilizing low-dose cyclophosphamide and total body
      irradiation.
AB  - Five patients with confirmed Fanconi's anemia (FA) and myelodysplasia and/or
      leukemia underwent stem cell transplantation (SCT) from related donors at KFSHRC.
      The median age at SCT was 12.6 year (range, 6.2-15 years). Conditioning regimen
      consisted of cyclophosphamide (CY) 5 mg/kg/day i.v. for 4 days, total body
      irradiation (TBI) 450 cGy in a single dose. Graft-versus-host disease (GVHD)
      prophylaxis was with cyclosporine and antithymocyte globulins (ATG). The median
      time to engraftment (defined as ANC>/=0.5 x 10(9)/l) was 16 days (range, 12-26
      days). The median time to a self-sustaining platelet count of >/=20 x 10(9)/l was
      27 days (range, 12-40 days). All patients engrafted. Two patients developed acute
      GVHD; one of the gut (grade 3) and the other of the skin (grade 1), and one
      patient developed chronic GVHD of the liver. Four are alive and well with no
      evidence of the disease; one patient died of bacterial sepsis after controlling
      her GVHD and clearing her pulmonary aspergillosis and CMV infection. We conclude
      that the use of low-dose CY plus TBI in patients with FA and MDS/AML undergoing
      SCT is adequate; the regimen is well tolerated and may be curative for such
      patients.

PMID- 14578934
TI  - Structure of HCV IRES domain II determined by NMR.
AB  - Complex RNA structures regulate many biological processes, but are often too
      large for structure determination by NMR methods. The 5' untranslated region (5'
      UTR) of the hepatitis C viral (HCV) RNA genome contains an internal ribosome
      entry site (IRES) that binds to 40S ribosomal subunits with high affinity and
      specificity to control translation. Domain II of the HCV IRES forms a 25-kDa
      folded subdomain that may alter ribosome conformation. We report here the
      structure of domain II as determined using an NMR approach that combines short-
      and long-range structural data. Domain II adopts a distorted L-shape structure,
      and its overall shape in the free form is markedly similar to its 40S subunit
      bound form; this suggests how domain II may modulate 40S subunit conformation.
      The results show how NMR can be used for structural analysis of large biological
      RNAs.

PMID- 14578935
TI  - Cellular stabilization of the melatonin rhythm enzyme induced by nonhydrolyzable
      phosphonate incorporation.
AB  - Serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase, AANAT)
      controls daily changes in the production and circulating levels of melatonin.
      Here, the significance of the phosphorylation of AANAT was studied using a
      semisynthetic enzyme in which a nonhydrolyzable phosphoserine/threonine mimetic,
      phosphonomethylenealanine (Pma), was incorporated at position 31 (AANAT-Pma31).
      The results of studies in which AANAT-Pma31 and related analogs were injected
      into cells provide the first direct evidence that Thr31 phosphorylation controls
      AANAT stability in the context of the intact cells by binding to 14-3-3 protein.
      These findings establish Thr31 phosphorylation as an essential element in the
      intracellular regulation of melatonin production. The application of Pma in
      protein semisynthesis is likely to be broadly useful in the analysis of protein
      serine/threonine phosphorylation.

PMID- 14578936
TI  - Trisoxazole macrolide toxins mimic the binding of actin-capping proteins to
      actin.
AB  - Marine macrolide toxins of trisoxazole family target actin with high affinity and
      specificity and have promising pharmacological properties. We present X-ray
      structures of actin in complex with two members of this family, kabiramide C and
      jaspisamide A, at a resolution of 1.45 and 1.6 A, respectively. The structures
      reveal the absolute stereochemistry of these toxins and demonstrate that their
      trisoxazole ring interacts with actin subdomain 1 while the aliphatic side chain
      is inserted into the hydrophobic cavity between actin subdomains 1 and 3. The
      binding site is essentially the same as the one occupied by the actin-capping
      domain of the gelsolin superfamily of proteins. The structural evidence suggests
      that actin filament severing and capping by these toxins is also analogous to
      that of gelsolin. Consequently, these macrolides may be viewed as small molecule
      biomimetics of an entire class of actin-binding proteins.

PMID- 14578937
TI  - Arytenoid dislocation: a new diagnostic and treatment approach.

PMID- 14578938
TI  - Pathogenesis and protection of ischemia and reperfusion injury in myocardium.
AB  - The important factors that influence the progress of ischemic cardiac lesion are
      blood flow condition and abnormal cardiac metabolism. Myocardial ischemia is
      promoted by either an increase in oxygen demand or a shortage of oxygen supply.
      The Na(+)-Ca(++) ion exchange mechanism is very important for myocardial
      contraction and cell damage. Na(+)-K(+)ATPase and Ca(++)ATPase are enzyme
      histochemically localized in subsarcolemmal cisterns, sarcolemmal reticulum and
      capillary endothelium, and keep myocardial function. These ATPases are impaired
      by anoxia, superoxides and free radicals. The reduction of O(2) results in the
      production of superoxides as well as hydrogen peroxide (H(2)O(2)). H(2)O(2) is
      highly diffusible and induces cell damage. H(2)O(2) appears to affect not only
      lipids but also intramembranous proteins embedded in the cell membrane. The
      hydroxyl radical (OH) also participates in lipid hyperoxidation. In the
      pathogenesis of ischemic and/or reperfused heart disease, ischemia induces rapid
      or gradual changes in all membrane systems and causes reversible or irreversible
      injury including necrotic and apoptotic cell death. Advanced glycation end
      products (AGEs) accumulation induced by diabetic conditioning is an etiologic
      factor inducing cardiomyopathy. The AGEs protein affects cell changes such as
      increased number, transformation, functional disturbance and cytokine
      elimination. In coronary arteries, the migration of smooth muscle cells caused by
      the taking up of AGEs proteins through the receptor (RAGE), and cytokine
      discharge are suggested. AGEs accumulation may induce diabetic macroangiopathy
      through RAGE, and the increase in the level of RAGE expression by endothelial
      cells could be a reason that diabetes mellitus accelerates atherosclerosis. On
      the other hand, we also reported that hyperglycemia was a promoting factor of
      ischemic heart injury in diabetic animals. Ischemic preconditioning is a useful
      phenomenon that limits myocardial damage. We foused on protein kinase C (PKC),
      mitogen-activated protein kinase (MAPK) and mitochondrial ATP-dependent potassium
      (mitoK(ATP)) channel as mediator or end which effector are necessary for
      adaptation. The opening of the mitoK(ATP) channel induces the depolarization of
      mitochondria, reducing Ca(++)overload during reperfusion. The regeneration of
      myocardial cells is confirmed using embryonic stem cells. Myocardial cells that
      exhibit self-pulsation are generated from mesenchymal stem cells in mesodermal
      tissues of the bone marrow.

PMID- 14578939
TI  - Randomized trial comparing in-situ radiofrequency ablation and Milligan-Morgan
      hemorrhoidectomy in prolapsing hemorrhoids.
AB  - The Milligan-Morgan (MM) operation is the most widely practiced procedure for
      prolapsed hemorrhoids. But it is also associated with a fair amount of
      postoperative pain, a long period of convalescence, and complications like
      bleeding and anal stenosis. The aim of this study was to evaluate the efficacy of
      in-situ radiofrequency ablation (RA) of hemorrhoids. During a 6-month period, 40
      patients with grade 3 hemorrhoids were prospectively randomized for RA (21
      patients) or MM hemorrhoidectomy (19 patients). Patients were evaluated for
      operative time, postoperative pain, time to return to work and occurrence of
      early and late complications. Duration of surgery was significantly higher in the
      MM group (p<0.0001). Postoperative hospitalization was longer in the MM group
      (p<0.001). The post defecation pain and pain at rest were much less in the RA
      group (p<0.001). Wound healing period (16.3 vs. 37.5 days) and time to return to
      work (7.3 vs. 18.3 days) were other significant findings. Early complications
      occurred more frequently in the MM group, but late complications like external
      skin tags [4 patients vs. 2 patients] and one asymptomatic recurrence was noted
      in the RA group. In-situ RA of prolapsing hemorrhoids is a quick and bloodless
      procedure. It is associated with significantly less postoperative pain, shorter
      hospital stay and early return to normal activity. It can be considered as an
      alternative to conventional hemorrhoidectomy.

PMID- 14578940
TI  - Biological behavior of mucoepidermoid carcinoma of the esophagus.
AB  - Mucoepidermoid carcinoma of the esophagus (MEC) is uncommon and has not been
      fully investigated. The biological behavior and clinical aspects of MEC were
      studied. The clinical features of eight patients with MEC were compared with 51
      cases of squamous cell carcinoma of the esophagus (SCC). Proliferating cell
      nuclear antigen (PCNA), p53, and carcinoembryonic antigen (CEA) were stained in
      the resected specimens by immunohistochemistry. Seven out of 8 cases (87.5%) had
      stage III by TNM classification. Four cases died of widespread metastases and 2
      cases died of local recurrence within 2 years after the surgery. Neither
      chemotherapy and radiotherapy were effective against MEC. Overall median survival
      periods were 10.8 months for MEC and 32.1 months for SCC (P<0.05). When patients
      in stage III alone were compared, MEC tended to have a worse prognosis than SCC
      (P=0.058). Immunohistochemical studies revealed that the positive rates of PCNA
      and CEA were significantly higher in MEC than in SCC (P<0.05), while there was no
      significant difference in p53 positive rate. Esophageal MEC had an aggressive
      biological nature and was resistant to adjuvant therapies. The poor prognosis of
      esophageal MEC may be caused by high proliferative and metastatic potential.

PMID- 14578941
TI  - Change of the mitochondrial distribution in mouse ooplasm during in vitro
      maturation.
AB  - Mitochondria (mt) have been reported to be closely related to the maturation of
      mammalian oocytes, but their function in oocyte maturation has not been
      elucidated. In this study, we examined the kinetics of mt and chromatin
      configuration during in vitro maturation of mouse oocytes to clarify the
      relationship between oocyte maturation and mitochondrial distribution
      morphologically. Oocytes were recovered from 6-to 8-wk-old ICR strain female
      mice. Germinal vesicle (GV) -stage oocytes were divided into 4 groups and
      cultured: group A, oocytes collected after pregnant mare serum gonadotropin
      (PMSG) injection; and group B, oocytes collected after PMSG-human chorionic
      gonadotropin injection. Groups A and B were subdivided into 2 groups: denuded
      oocytes (DO) and cumulus-enclosed-oocytes (CEO). At 0, 4, 8, 12 and 16 h from the
      onset of the culture, oocytes were fixed and stained to visualize alpha-tubulin,
      chromatin and mt using confocal laser scanning microscopy (CLSM). It was observed
      that mt aggregated around the nucleus from the GV-stage through progression to
      germinal vesicle breakdown (GVBD). With the movement of the nucleus, mt were
      concentrated around the nucleus and polarized. The maturation rate (the rate of
      the first polar body extrusion) and the fertilization rate of CEO were
      significantly higher than that of DO in both groups A (p<0.01) and B (p<0.05).
      During the GV-stage to GVBD, the rate of mitochondrial aggregation around the
      nucleus tended to be high in group A (CEO). The rates of mitochondrial
      polarization in MI and MII oocytes were 76.1% with in-vitro maturation (IVM) and
      86.7% with in-vivo-maturation, respectively; the rate was significantly higher in
      in-vivo-maturation-oocytes than in IVM-oocytes (p<0.01). From the present results
      it can be considered that aggregaton of mitochondria around the nucleus was
      essential for maturation, fertilization and development.

PMID- 14578942
TI  - [Morphologic analysis of Japanese adult sacroiliac joint using computed
      tomographic images].
AB  - PURPOSE: To study the relationship of angles in adult sacroiliac joints (SJ) with
      laterality, age, gender, degeneration, childbearing in different locations.
      METHODS: The study was performed in 92 healthy Japanese adult volunteers (46
      males and 46 females, aged 21 approximately 86 years) who had no low back
      complaints. Axial computed tomographic (CT) images were obtained using an X-VIGOR
      apparatus (Toshiba Medical Inc. Japan). The angle measurements were taken
      directly using soft NIH Image 1.61 (Scion Inc. USA). We examined possible
      factors. Statistical evaluation was calculated using t-test by soft SPSS (SPSS
      Inc. Japan). RESULTS: Our findings indicated that SJ angles had no relationships
      with laterality, gender. But from upper part to lower part, the average of SJ
      angle was 7.61 degrees +/-8.7 degrees, 5.16 degrees +/-7.3 degrees, -0.85 degrees
      +/-7.3 degrees respectively in the left and 6.56 degrees +/-9.4 degrees, 4.10
      degrees +/-7.2 degrees, -2.30 degrees +/-7.0 degrees in the right. The difference
      is significant between lower part and upper-middle part (P<0.05). CONCLUSION: Our
      results provided new anatomic and morphological data for better understandings of
      SJ in the clinic work.

PMID- 14578943
TI  - [Current status of regenerative therapy. Regeneration of peripheral nerves].

PMID- 14578944
TI  - [Tissue engineering of the phalanx and phalangeal joint].

PMID- 14578945
TI  - [Versatility of adipose tissue as a source of stem cells].
AB  - The stem cells are promising for future cell-based therapy such as tissue
      engineering or regenerative medicine. Although Embryonic Stem Cells (ESCs) are
      theoretically highly beneficial, there are various limitations on their use posed
      by cell regulations and ethical considerations. Therefore, adult stem cells are
      considered to be highly available with neither ethical nor immunoreactive
      considerations as long as they are of autologous tissue origin. Much of work has
      focused on the Mesenchymal Stem Cells (MSCs) isolated from bone marrow stroma,
      which have been shown to possess adipogenic, osteogenic, chondrogenic, myogenic
      and neurogenic potential in vitro. However bone marrow procurement is severely
      painful for patients and the harvested cells yields low number. Our preliminary
      studies have identified a putative stem cell population isolated from human
      adipose tissue. This cell population, termed Processed Lipoaspirate Cells (PLA
      Cells), is found to differentiate into adipogenic, osteogenic, chondrogenic and
      myogenic lineage in vitro in lineage-specific culture media. In addition to these
      findings, our recent data shows that PLA cells can be induced to differentiate
      into neural precursors, which are of an ectodermal origin. Furthermore, PLA cells
      express multiple CD marker antigens similar to those observed on MSCs. Finally,
      some of PLA clonal cells have capabilities of differentiate into adipogenic,
      osteogenic and chondrogenic lineage. These findings suggest that human PLA have a
      mesodermal stem cell population. Since human adipose tissue is ubiquitous, easily
      obtainable in large quantity under local anesthesia with little patient
      discomfort, it may be an alternative stem cell source for mesenchymal tissue
      regeneration and engineering.

PMID- 14578946
TI  - [Cell-mediated gene therapy using bone marrow derived cells towards regenerative
      medicine].

PMID- 14578947
TI  - [Present status of therapeutic angiogenesis by autologous bone marrow cell
      implantation for refractory chronic peripheral arterial disease and ischemic
      heart disease].

PMID- 14578948
TI  - [Development of the protein therapeutics using the super anti-cell death factor
      FNK].
AB  - A powerful artificial anti-apoptotic factor will be useful for the reproductive
      therapies for many diseases by prolonging survival of stem cells. For
      constructing it, we designed the super anti-apoptotic factor by disturbing three
      intramolecular polar interactions among alpha-helix structures of Bcl-xL. The
      resultant mutant Bcl-xL, named FNK, was expected to make the pore-forming domain
      more mobile and flexible than the wild-type. When overexpressed in Jurkat cells,
      FNK was markedly more potent in prolonging survival following apoptosis-inducing
      treatment with a kind of cell death cytokines (anti-Fas), a protein kinase
      inhibitor (staurosporine), cell cycle inhibitors (TN-16, camptothecin,
      hydroxyurea and trichostatin A) or oxidative stress (hydrogen peroxide and
      paraquat) than wild-type Bcl-xL. Furthermore, the transfectants of FNK became
      more resistant against a calcium ionophore and even a heat treatment than wild
      type Bcl-xL. In addition, FNK showed marked anti-apoptotic activity in CHO and
      Jurkat cells deprived of serum. Thus, FNK may be the first mutant generated by
      site-directed mutagenesis of Bcl-xL with an enhance gain-of-function phenotype.
      Next, we tried to transduce the FNK protein into cells. Protein therapeutics has
      the advantage of delivering proteins in a short period of time. We have
      engineered the anti-apoptotic bcl-x gene to generate the super anti-apoptotic
      factor, FNK, with a more powerful cytoprotective activity. In this study, we
      fused the protein transduction domain (PTD) of the HIV/Tat protein to FNK, and
      used the construct in an animal model of ischemic brain injury. When added into
      culture media of human neuroblastoma cells and rat neocortical neurons, PTD-FNK
      rapidly transduced into cells and localized to mitochondria within 1 hr. It
      protected the neuroblastomas and neurons against staurosporine-induced apoptosis
      and glutamate-induced excitotoxicity, respectively. The cytoprotective activity
      of PTD-FNK was found at concentrations as low as 0.3 pM. Additionally, PTD-FNK
      affected the cytosolic movement of calcium ions, which may relate to its
      neuroprotective action. Immunohistochemical analysis revealed that myc-tagged PTD
      FNK (PTD-myc-FNK) injected intraperitoneally into mice can have access into brain
      neurons. When injected intraperitoneally into gerbils, PTD-FNK prevented delayed
      neuronal death in the hippocampus caused by transient global ischemia. These
      results suggest that PTD-FNK has a potential for clinical utility as a novel
      protein therapeutic strategy to prevent cell death in the brain. Thus, the
      protein delivery system will be useful to make cells survived for a long time
      during the differentiation of stem cells in the reproductive therapies.

PMID- 14578949
TI  - A case of maternal reaction due to fetomaternal transfusion.
AB  - We present here a case of maternal reaction to fetomaternal transfusion
      complicated by subchorionic hemorrhage. A 40-year-old woman, gravida 2, para 0,
      was admitted to our hospital at 25 weeks' gestation because of high blood
      pressure. On the morning of 32 weeks and 2 days' gestation, she developed sudden
      onset nausea, dyspnea and regular uterine contractions. Blood pressure was 80/50
      mmHg and pulse was 110 beats/minute. At this time, her WBC, hemoglobin and
      platelets were decreased significantly. Two hours after onset, the patient's
      condition improved spontaneously. Increased serum alpha-fetoprotein level (3.0
      multiple of median) was observed. She was suggested to be a case of acute
      fetomaternal transfusion.

PMID- 14578950
TI  - Uterine perforation following manual removal of the placenta.
AB  - We present here a case of uterine perforation following manual removal of the
      placenta during the third stage of normal labor. Total abdominal hysterectomy was
      performed, and the 4x3-cm perforation of the uterus and placenta accreta were
      confirmed. In this case, the round ligament covering the hematoma prevented
      bleeding into the peritoneal cavity and peritonitis. Manual removal of the
      placenta should be performed carefully following ultrasonographic assessment for
      placental abnormalities such as placenta accreta.

PMID- 14578951
TI  - [Angle-closure glaucoma: important points in the diagnosis and follow-up].
AB  - A 74-year-old woman visited her local physician complaining of fever, cough,
      headache, hyperemic left conjunctiva, and blurred vision. She was diagnosed as
      having common cold and medicated for it, and later, she visited our department.
      She had a shallow left anterior chamber with moderately dilated pupil.
      Gonioscopic examination of the left eye revealed a narrow angle corresponding to
      grade 1 by Shaffer grading system. Left intraocular pressure was 16 mmHg. She was
      diagnosed to have had a spontaneous recovery from a subacute attack of angle
      closure glaucoma. Laser iridectomy was performed and she was put on a regular
      ophthalmological follow-up. Three years later, she experienced an attack of left
      angle-closure glaucoma secondary to lens intumescence. She was treated by
      phacoemulsification and aspitaion which resulted in the eventual cure.

PMID- 14578952
TI  - Year in review: communicable disease surveillance, 2002.

PMID- 14578953
TI  - Priorities for communicable disease control in New South Wales, 2003.

PMID- 14578954
TI  - FactSheet: Viral gastroenteritis.

PMID- 14578956
TI  - Quantitative health risk assessment.

PMID- 14578955
TI  - Communicable Diseases Report, NSW, for July 2003.

PMID- 14578957
TI  - What does it mean when the risk assessment says 4.73 x 10(-5)?

PMID- 14578958
TI  - Suspected pesticide poisoning: a back-of-the-envelope health risk assessment.

PMID- 14578959
TI  - But you don't have to live here! Risk assessment and contaminated sites: a case
      study.

PMID- 14578960
TI  - Risk assessment for the consumption of fish with elevated selenium levels.

PMID- 14578961
TI  - Taking the plunge: recreational water quality guidelines.

PMID- 14578962
TI  - Influenza.

PMID- 14578963
TI  - Communicable Diseases Report, NSW, for June 2003.

PMID- 14578964
TI  - New trends in medical education. The clinical skills laboratories.
AB  - A clinical skills laboratory or center is a facility in which students,
      physicians, nurses and other health care professionals learn clinical,
      communication and information technology skills to a specified level of
      competence prior to or coordinated with direct patient contact. The purpose of
      the clinical skill laboratory is to support the acquisition, maintenance and
      enhancement of the clinical skills of students in health care professions. Within
      this non-threatening environment, patient volunteers, simulated patients,
      mannequins and information technology are employed to provide hands-on learning
      experiences for the practice of the essential clinical skills. The skills
      laboratory helps to ensure that all students have necessary learning
      opportunities and appropriate assessment and feedback before approaching real
      patients. As more and more schools integrate skills laboratories into their
      curricula, it is important to review this new trend, to introduce the reader to
      its nature, factors that led to its development, advantages and problems related
      to its implementation. This review will also suggest some guidelines that may
      help in overcoming the implementation problems.

PMID- 14578965
TI  - Peripartum cardiomyopathy searching for a better understanding.
AB  - Congestive heart failure is an uncommon complication of pregnancy with
      potentially life-threatening consequences. Peripartum cardiomyopathy (PPCM) is a
      disease of unknown cause in which severe left ventricular dysfunction occurs
      during late pregnancy or the early puerperium. In the past, the diagnosis of this
      entity was made on clinical grounds; however, modern echocardiographic techniques
      have allowed more accurate diagnoses by excluding cases of diseases that mimic
      the clinical symptoms and signs of heart failure. Risk factors for peripartum
      cardiomyopathy include advanced maternal age, multiparity, African descent,
      twinning, and long-term tocolysis. An extensive search for the causes of
      peripartum cardiomyopathy has been unrevealing. Treatment does not differ from
      treatment of idiopathic cardiomyopathy. The prognosis of peripartum
      cardiomyopathy is related to the recovery of ventricular function. Caution is
      advised in recommending subsequent pregnancy, especially if left ventricular
      dysfunction is persistent. In this review, we will discuss different aspects of
      PPCM as the initial patient contact, obstetricians and family practitioners must
      recognize this malady early and rapidly institute the proper medical therapy
      directed towards the congestive state.

PMID- 14578966
TI  - Molecular analysis of the spinal muscular atrophy and neuronal apoptosis
      inhibitory protein genes in Saudi patients with spinal muscular atrophy.
AB  - OBJECTIVE: Spinal muscular atrophy (SMA) is a common, often fatal, autosomal
      recessive disease leading to progressive muscle wasting and paralysis as a result
      of degeneration of anterior horn cells of the spinal cord. The prevalence of SMA
      cases in the Kingdom of Saudi Arabia (KSA) is much higher than the European and
      North American population. Deletions or mutations in 2 genes, telomeric form of
      the survival motor neuron (SMN1) and the neuronal apoptosis inhibitory protein
      (NAIP), are known to be associated with SMA. The aim of this study is to examine
      the deletions or interruptions of the SMN1 and NAIP genes in Saudi patients.
      METHODS: The study included 121 Saudi SMA patients [type I (60 patients); type II
      (26 patients); and type III (35 patients)]. The deletions or interruptions of the
      SMN1 and NAIP genes were detected by using polymerase chain reaction. The study
      was carried out at the King Fahad National Guard Hospital, Riyadh, KSA between
      2000 and 2002. RESULTS: The homozygous deletions of exons 7 and 8 of the SMN1
      gene were found in 94% and 87% of the patients. Exon 5 of the NAIP gene was
      deleted in 70%, but its deletion was more frequent in SMA type I (93%) as
      compared to type II (54%) and type III (43%). Seven patients with SMA diagnosis
      did not show any of the above homozygous deletions. All 230 control subjects had
      at least one copy of both SMN1 and NAIP genes, as expected. CONCLUSION: Our
      results demonstrate that the deletion rate (94%) of the SMN1 gene in Saudi SMA
      patients is similar, irrespective of types, compared with patients of other
      ethnic groups. We also show that the incidence of NAIP deletion is higher in the
      more severe SMA cases and the dual deletion of the SMN1 and NAIP genes are more
      common in Saudi SMA type I patients compared with patients of other ethnic
      groups.

PMID- 14578967
TI  - Familial Mediterranean fever mutation frequencies and carrier rates among a mixed
      Arabic population.
AB  - OBJECTIVE: Familial Mediterranean Fever (FMF) is an autoinflammatory periodic
      disorder characterized by febrile and painful attacks due to inflammation
      involving the serosal membranes. The gene implicated in this disorder, MEFV, has
      been cloned and mutations in its coding regions have been identified. We aimed at
      identifying the frequency of MEFV mutations and carrier frequency in a mixed
      Arabic population. METHODS: We identified 29 probands from 29 unrelated sibships
      segregating the disorder and representing the affected individual cohort. We
      screened 200 anonymous deoxyribonucleic acid (DNA) samples, representing a
      healthy adult cohort, for the mutations found to be common in the affected
      individual cohort. We also, screened anonymous DNA samples from 4 Arabic
      countries, namely, Egypt (231), Syria (225), Iraq (176) and the Kingdom of Saudi
      Arabia (107) thus enlarging our healthy adult cohort. The study was carried out
      between 1999 and 2002 at Jordan University of Science and Technology, Irbid and
      the University of Jordan, Amman, Jordan. RESULTS: Out of the 58 alleles of the 29
      probands, only 31 mutations were identified and M694V and V726A are the most
      common. The mutation E148Q was the most common among the healthy adult cohort,
      but was not present in affected individuals. The collective mutant allele
      frequency "q" was 0.101. The expected carrier rate was 18.1% (one in 5.5) while
      the observed carrier rate was 18.4% (one in 5.4). CONCLUSION: E148Q has reduced
      penetrance and thus, a proportion of the individuals genetically affected with
      FMF remain asymptomatic. M694I and M680I are more prevalent in the affected
      individuals cohort, which points to their higher penetrance. The overall carrier
      rate is one in 5, but the selective heterozygote advantage could not be
      demonstrated in this study due to the relatively small sample size.

PMID- 14578968
TI  - Candidemia and the susceptibility pattern of Candida isolates in blood.
AB  - OBJECTIVE: Candida species has become one of the most common blood isolates as
      well as one of the leading causes of nosocomial bloodstream infections. The
      purpose of our study was to determine the prevalence of Candida species among our
      bloodstream infecting organisms and the susceptibility pattern of the Candida
      isolates to antifungal agents. METHODS: A prospective study was carried out in
      the Division of Microbiology, King Khalid National Guard Hospital, Jeddah,
      Kingdom of Saudi Arabia of all positive blood cultures for Candida species. The
      study took place from 1st January 1998 to March 2002. Identification and
      susceptibility pattern of isolates were determined by the Candifast technique to
      amphotericin B, fluconazole, nystatin, Flucytosine, econazole, ketoconazole and
      miconazole. RESULTS: Over a 2-year period, 17,916 blood cultures were performed
      in our hospital. There were 2,972 positive cultures, of which 83 (2.8%) patients
      had Candida species isolated from their bloodstream. Of these, 38 (46%) were
      Candida albicans (C.albicans). The remaining 45 strains were made up of Candida
      tropicalis 9 (10.8%); Candida parapsilosis 9 (10.8%); Candida species 9 (10.8%);
      Candida guilliermondi 6 (7.2%); Candida krusei 5 (6%); Candida glabrata 4 (4.8%);
      Candida pseudotropicalis 2 (2.4%) and Trichosporon species 1 (1.2%). All Candida
      species were susceptible to amphotericin B. However, only 18 (47%) out of 38
      C.albicans were susceptible to fluconazole, while only 8 (17.7%) of 45 non
      C.albicans strains were susceptible to this drug. CONCLUSION: The susceptibility
      of C.albicans to fluconazole in our hospital using the Candifast method is very
      low (47%). These results need to be confirmed by carrying out the Etest or the
      NCCLS M27-A method to confirm the true susceptibilities of Candida strains in our
      locality.

PMID- 14578969
TI  - Bacteremia and septicemia in diabetic patients in Western Saudi Arabia.
AB  - OBJECTIVE: The present study aims to define the pattern of bacteremia with
      clinical sepsis in diabetic patients at King Abdul-Aziz University Hospital
      (KAUH), Jeddah, Kingdom of Saudi Arabia (KSA), in relation to the type of
      infection, microbial pattern, source, complication, outcome, and the risk factors
      associated with high mortality. METHODS: Retrospective study of adult diabetic
      patients with bacteremia and septicemia admitted to KAUH during a 2 years period
      between January 2000 through to December 2002 was carried out. RESULTS: A total
      of 4850 blood culture were submitted to the Microbiology Laboratory of KAUH over
      a 2 years period. Two hundred and ninety (6%) cases had positive blood cultures,
      70 were diabetic patients with an incidence rate of 24% with p-value of 0.043
      which is statically significant. Urinary tract infection was the most common
      source of bacteremia in our study group with Escherichia coli as the most
      frequent organism in 62%. Mortality rate was 44%. Old age was an important risk
      factors for high mortality with p-value 0.011, which is statically significant.
      Other risk factors included comorbidity associated with diabetes, septic shock,
      mechanical ventilation and disseminated intravascular coagulation. CONCLUSION:
      Increase age was one of the important risk factors for high mortality rate in our
      study group. Good empiric antibiotics coverage should be instituted early in high
      risk groups.

PMID- 14578970
TI  - Imported malaria infections diagnosed at the Malaria Referral Laboratory in
      Riyadh, Saudi Arabia.
AB  - OBJECTIVE: To determine epidemiological characteristics of imported malaria
      infections in Riyadh, Kingdom of Saudi Arabia, based on retrospective analysis of
      laboratory records within the Central Laboratory. METHODS: Records of the Malaria
      Referral Laboratory in Riyadh, Kingdom of Saudi Arabia (KSA) were reviewed for
      the past 6 years: 1416-1421 Hejri inclusive (1996-2001 Gregorian). The dates of
      blood films were converted to Gregorian calendar in addition to the Hejri dates
      already used in the records. Data collected included the date of film, age, sex,
      nationality and parasitological findings in the film. All data was entered and
      analyzed using statistical package for social sciences computer software.
      RESULTS: The annual mean number of positive slides was 212 +/- 78. Positive
      slides were reported at the rate of 18 /100,000 among 137,402 potential blood
      donors screened during this period. The overall slide positivity was 12.9% among
      suspected cases referred from hospitals and 9.5% among those referred from health
      centers and private clinics. Most positive slides were from Saudis (36.6%),
      Sudanese (30.9%), Indians (13.9%), Pakistanis (8%) and Yemenis (5%). The type of
      malaria infection varied in the different nationalities, reflecting the pattern
      of endemicity at the source of infection. Positive cases show a marked
      seasonality in Saudis, reflection seasonal transmission of the disease in the
      endemic areas. CONCLUSION: Although there is no active malaria transmission in
      Riyadh KSA, imported infections still poses a significant health problem. A high
      index of suspicion should be maintained in those with suggestive travel history.
      Efforts to reduce the incidence of transfusion malaria should aim at formulation
      of appropriate policies for selection of blood donors and for screening of blood.

PMID- 14578971
TI  - Pattern of admission to hospitals during muslim pilgrimage (Hajj).
AB  - OBJECTIVE: The pattern of medical conditions necessitating admission differs
      according to the weather condition in that particular year. Previous studies had
      been conducted during the hot weather, none over the last 10 years, were carried
      out during, the milder weather we are experiencing. The aim of this study is to
      establish the pattern of admission during this mild weather and to elucidate the
      possible risk factors. METHODS: A prospective study was performed in 4 hospitals
      in 2 different locations in Al-Mashaer, Kingdom of Saudi Arabia. Data were
      collected during one working shift in 2 hospitals in Arafat on the 9th of Dhul
      Hijjah 1422, corresponding to 21st of February 2002, and another working shift in
      2 hospitals in Mina on the 10th of Dhul Hijjah 1422, corresponding to 22nd of
      February 2002. RESULTS: A cohort of 76 patients from Arafat hospitals and 84
      patients from Mina hospitals were included (total 160 patients). Males
      constituted 62% and females 38% with the median age of 60 +/- 15 years. The
      respiratory system was the most commonly affected (57%), followed by
      cardiovascular system (19.4%), and gastrointestinal tract (GIT) in 6.3% of cases.
      There were only 3 cases of heat-related admissions with only one confirmed case
      of heat stroke. Similarly, only one case of meningitis was confirmed in this
      cohort. Pneumonia was encountered in 63 cases (39.4%) and exacerbation of asthma
      and chronic obstructive pulmonary diseases (COPD) in 23 cases (14.4%). Pre
      existing co-morbid medical conditions had included bronchial asthma and COPD
      (22.5%), hypertension (17.5%), and Diabetes mellitus (15%). Short-term follow up
      (24-48 hours) identified 2 deaths (1.3%), 94 patients (59%) were transferred to
      other secondary or tertiary care facilities and 64 (40%) were discharged home.
      CONCLUSION: Hospital admission during Hajj is related to old age and occurs in
      patients with associated co-morbid conditions. During this mild weather lower
      respiratory tract infections and exacerbation of bronchial asthma and COPD are
      the most commonly encountered diseases during Hajj.

PMID- 14578972
TI  - Response of Sudanese doctors to domestic violence.
AB  - OBJECTIVE: The aim of this study was to assess the awareness, and response of the
      Sudanese doctors to domestic violence. METHODS: The study was carried out among
      the doctors of the Police University Hospital, Khartoum, Sudan. Self-administered
      questionnaires were distributed to all doctors who were attendants at the
      hospital, one morning in July 2002. The information required from the surveyed
      doctors included their familiarity, and views on domestic violence as a health
      problem, number of cases of abuse encountered, barriers to diagnose or screen
      cases, their views on intervention beyond physical treatment and if they had been
      taught or trained in domestic violence. RESULTS: Out of 142 doctors who received
      the questionnaires, 102 returned it giving a response rate of 71.8%. The
      respondent's ages ranged from 25-54 years; 53 were female (51.9%); and 32 (31.3%)
      had experience of more than 10 years. Forty-three doctors (42.1%) had a fair
      knowledge of the concept of domestic violence, 28 (27.4%) viewed it as a
      worthwhile health problem and 21 (20.5%) reported encountering 1-2 cases in the
      last year. Barriers to screen cases included a lack of knowledge and training,
      insufficient time at clinics and fear of problems with perpetrators. The female
      gender and long professional experience had positive correlations with a better
      knowledge regarding violence and the desire to intervene beyond physical
      treatment (P<0.005). CONCLUSION: Our study indicated clearly the missing role of
      the medial profession in recognition and helping the victims of domestic
      violence. The authors discussed several suggestions to promote the role of
      doctors in addressing this problem.

PMID- 14578974
TI  - The knowledge and practices of oral hygiene methods and attendance pattern among
      school teachers in Riyadh, Saudi Arabia.
AB  - OBJECTIVE: The aim of this study was to find out the knowledge and practices of
      oral hygiene methods among primary and secondary school teachers in Riyadh,
      Kingdom of Saudi Arabia (KSA). METHODS: The study was carried out using a self
      administered questionnaire. Four hundred and seventy teachers, male 236 (50.2%)
      and female 234 (48.8%) responded with a response rate of 85.5%. The study was
      conducted during October to December 2001 at primary and secondary schools in
      Riyadh City, KSA. RESULTS: Almost 86% of male and 90% of female teachers felt
      that dental caries is due to the wrong method of tooth brushing, while sugar and
      sugary drinks were considered the main factor by 90% of male and 98% of female
      teachers. Seventy-five percent of male and 72% of female teachers considered
      irregular tooth brushing a cause of gums disease with 32% of male and 39% of
      female teachers not knowing details with regards to microbial relationship of gum
      disease. Tooth brushing preference was common among 45% male and 49% female
      teachers due to perceived effect of better cleaning, while almost an equal
      percentage of male and females (62%) used miswak due to Sunnah. Thirty-three
      point five percent of female teachers brushed 3 times a day as compared to 19%
      male teachers. On daily basis brushing 3 times, a day was common among >5000 SR
      monthly income group. Male teachers preferred horizontal tooth brushing (40%)
      while female teachers preferred circular tooth brushing (45%). Miswak was more
      commonly used by male teachers as compared to female teachers. Female school
      teachers had a higher income as compared to male schoolteachers. Thirty-two
      percent of females and 28% of male teachers were regular attendees to the
      dentist. Males were more satisfied by their oral health as compared to female
      teachers and 56% of male and 63% of female teachers visited the dentist only on
      having pain (toothache). CONCLUSION: It is concluded that there is much
      resemblance in knowledge and practice of oral hygiene habits among male and
      female schoolteachers and there is a need to enhance their knowledge regarding
      oral health and disease. Both need more awareness regarding oral health promotion
      to have a positive role in school oral health education for their students in
      collaboration with oral health care workers.

PMID- 14578973
TI  - Treatment needs for dental caries in schoolchildren in Riyadh, Saudi Arabia. A
      follow up study of the oral health survey.
AB  - OBJECTIVE: To determine the magnitude and severity of treatment needs for dental
      caries of school children of Riyadh, Kingdom of Saudi Arabia (KSA), 14 years
      after the conduct of the Oral Health Survey (Phase I) (OHS (I)) in KSA. METHODS:
      Six hundred and two primary school first graders (primary school (PS)) (5-8 year
      old) and 205 intermediate school first graders (intermediate school (IS)) (11-14
      year-old) children were randomly selected, using stratified cluster random
      sampling, from schools of Riyadh, KSA during April 2001 to May 2001. All the
      children were examined for caries and treatment needs, using the World Health
      Organization criteria. RESULTS: Ninety-three percent of PS children required some
      type of restoration and 36.7% needed extractions. Ninety-five percent of IS
      children required restorations and approximately one-quarter were needed
      extractions. Amongst male PS children approximately 7 teeth needed one or more
      surface fillings, whereas 6 teeth of female PS children needed the same. Of the
      male IS children, 6.5 teeth needed one or more surface fillings, whereas 4 teeth
      of female IS children needed the same. These differences were all statistically
      significant. On average, one tooth of male children needed extraction, whereas
      approximately 0.7 teeth of female children needed the same. The difference was
      also significant. There were significant differences between urban and rural
      children for various types of treatment needs. However, nationality of the
      children did not show any significant effects on treatment needs. CONCLUSION: The
      results indicate that the treatment needs for dental caries have increased in
      schoolchildren of Riyadh significantly 14 years after the conduct of OHS (I).

PMID- 14578975
TI  - Evaluation of 6 cardiac troponin assays in patients with acute coronary syndrome.
AB  - OBJECTIVE: An increasing body of evidence has demonstrated the value of
      strategies based on cardiac troponin (cTn) assays in the diagnosis, prognosis and
      monitoring of patients with acute coronary syndrome (ACS). We evaluated the
      performance and the practicability of 6 commercially available assays (5 cTnI and
      1 cTnT) in patients with ACS. METHODS: This study was carried out between October
      2001 and June 2002 at Armed Forces Hospital in collaboration with Prince Sultan
      Cardiac Center, Riyadh, Kingdom of Saudi Arabia. Blood samples from 96 patients,
      40 with and 56 without clinical evidence of myocardial injury, were used for the
      evaluation. Cardiac TnI assays were performed using 5 different immunoanalyzers
      AxSYM (Abbott Laboratories), Stratus CS (Dade Behring), ACS:180 (Bayer), Centaur
      (Bayer) and Immulite (Diagnostic Products Corporation) while cTnT was measured on
      the Elecsys (Roche) immunoanalyzer. The sensitivity, specificity and positive and
      negative predictive values (PV) were calculated for all assays. General and
      special features related to installation, routine operation, quality control and
      other various special parameters of each immunoanalyzer were evaluated (using the
      score of 1-5 for each parameter) and compared with those of other analyzers.
      RESULTS: The highest reliability values were observed with Immulite, followed by
      AxSYM, then Stratus, then ACS:180, and Centaur, and lastly by Elecsys. The
      highest practicability values were observed with Elecsys, and Centaur, followed
      by AxSYM and the lowest values were observed with Stratus. CONCLUSION:
      Considering the combined performance and practicability score, the difference
      between the 10% coefficient variation cut off value and the 99th percentile
      value, and the difference in the relative reactivities to the various cTnI forms,
      the most favorable values were observed with AxSYM, followed by Immulite and
      Elecsys, then Centaur and Stratus, and lastly by ACS:180.

PMID- 14578976
TI  - Pregnancy and valvular heart disease.
AB  - OBJECTIVE: To review all cases of valvular heart disease during pregnancy in a
      regional Saudi-Arabian population between 1993-1997, determine its incidence,
      contributing factors and its effect on the outcome of pregnancy. METHODS: A
      retrospective study of 33,200 cases between 1993-1997 performed over a period of
      5 years in the Department of Obstetrics and Gynecology in King Khalid University
      Hospital, Riyadh, Kingdom of Saudi Arabia. Most patients were Saudi nationals
      (83.4%). Evidence of heart disease was detected in 166 pregnant women, an
      incidence of 0.5%. Valvular heart disease was present, either as a single valve
      involvement or in combination, in 76% of the patients. The remaining 24% were a
      miscellaneous group including patients with cardiomyopathies, or pulmonale and
      septal defects. The data collected was analyzed using Gold Stat Software Package.
      RESULTS: As a single valve disease, mitral valve involvement was predominant
      (94.5%), compared to aortic valve (5.5%). The most common condition involving
      mitral valve was the valve prolapse (39.2%), followed by mitral regurgitation
      (19.9%) and mitral stenosis (16.9%). Twenty-four percent of the pregnant women
      with valve disease had multiple valve involvement. Forceps were applied in 8.4%
      of the patients and ventouse deliveries in 1.2%. Cesarean section was performed
      in 3.6% of the cases, out of which 2.4% were emergency lower segment cesarean
      section and 1.2% were elective. No maternal or infant mortality occurred. All
      infants were normal and healthy with mean infant weight of 3.24 +/- 0.52 kg.
      Prophylactic antibiotics were administered in 83% of the patients. None of the
      patients, whether treated with antibiotics or not, developed infective
      endocarditis. CONCLUSION: Presence of valvular heart disease in our study did not
      appear to affect the outcome of pregnancy, but its accurate diagnosis and
      management demand a greater understanding of cardiovascular physiology and its
      pathophysiology in pregnancy, labor and the puerperium. The successful management
      of the woman with valvular heart disease in pregnancy required complete
      cooperation between the patient herself, the obstetrician, cardiologist,
      anesthetist and other supporting medical staff, to optimize the outcome for both
      the mother and her baby.

PMID- 14578977
TI  - Obstructed labor in a teaching hospital in Sudan.
AB  - OBJECTIVE: This study was aimed to deal with a serious obstetrical problem in Wad
      Medani Teaching Hospital, Medani, Sudan. The study reviewed the incidence of
      obstructed labor, its clinical presentation and methods of diagnosis. The study
      also includes the methods of treatment and its complications. METHODS: A
      prospective and descriptive study was carried out in Wad Medani Teaching
      Hospital, Medani, Sudan. Case notes were studied for all cases with obstructed
      labor received during the period 1 January 1997 to 31 December 1999. The data was
      analyzed. The literature was reviewed for similar studies. RESULTS: During the
      period 207 cases of obstructed labor were diagnosed. The total number of
      deliveries during the same period was 16221, giving an incidence of 1.27%. The
      most striking symptoms are tachycardia and low blood pressure, while the common
      sign is the non-engagement of the presenting part. The most common complication
      is septicemia. CONCLUSION: Obstructed labor remains a major obstetrical problem.
      Adequate antenatal care and proper care at delivery could prevent it. The
      obstructed labor should always be anticipated and the attendant should not wait
      for the advanced classical signs to make the diagnosis. Early intervention is
      associated with an excellent outcome.

PMID- 14578978
TI  - Fournier's gangrene in diabetic and renal failure patients.
AB  - OBJECTIVE: To report our experience in the management of 9 patients with
      Fournier's gangrene seen in our institute, to identify the most common prognostic
      variables in our patients, and to evaluate the outcome of aggressive management
      in patients with Fournier's gangrene. METHODS: We reviewed the medical records of
      9 patients admitted to King Abdul-Aziz University Hospital (KAUH) in Jeddah,
      Kingdom of Saudi Arabia from November 1999 until November 2002. Their age, sex,
      clinical presentation, predisposing factors, microbiology testing, management and
      prognosis were studied. RESULTS: Nine male patients were diagnosed and treated.
      The mean age was 68 years, 6 patients (66.6%) were diabetics and one of them had
      renal insufficiency not requiring dialysis, while 3 patients were on regular
      hemodialysis. Bacterial culture results revealed a single organism in 44.4%, and
      more than one organism in 55.6% of the cases. No anaerobes could be cultured, and
      one patient had Candida albicans. All patients had temporary suprapubic catheter
      diversion while stool diversion by colostomy was required in only one patient. In
      7 patients, aggressive debridement and parental antimicrobial were successful to
      eradicate the infection, whereas 2 patients (22.2% of the cases) died of
      uncontrolled sepsis. CONCLUSION: Fournier's gangrene is a very serious disease,
      understanding the criteria of early recognition of the disease, referral to the
      specialist, and aggressive debridement with the use of appropriate antimicrobial
      therapy will improve the outcome of the patients and decrease the mortality rate.

PMID- 14578979
TI  - Sub-optimal postprandial blood glucose level in diabetics attending the
      outpatient clinic of a University Hospital.
AB  - OBJECTIVE: To determine the frequency of diabetic patients who attained the
      optimal postprandial blood glucose level. METHODS: Cross-sectional study of type
      2 diabetic patients being followed at the medical outpatient clinic of King Abdul
      Aziz University Hospital, Jeddah, Kingdom of Saudi Arabia, from January 1999 to
      December 2001. Patients were classified according to postprandial blood glucose
      level into 3-categories; group-1 (<9 mmol/l), group-2 (9.1-10 mmol/l), group-3
      (>10 mmol/l). Other data such as age, sex, duration of diabetes, presence of
      hypertension, hyperlipidemia, smoking, obesity, ischemic heart disease was
      recorded as well as mortality. RESULTS: A total of 443 patients were studied with
      mean age of 55 years and equal male to female ratio. The mean 2-hour postprandial
      blood glucose level was 14 mmol/l. The majority of patients were in group-3
      (71%), while group-1 was 22% and group-2 was 7%. Patients with high 2-hour
      postprandial blood glucose (group-3) have a higher prevalence of hypertension
      [120/315 (38%) versus 31/97 (32%) p=0.01], hyperlipidemia [72/315 (23%) versus
      13/97 (13%) p=0.02], obesity [79/315 (25%) versus 18/97 (19%) p=0.04], ischemic
      heart disease [72/315 (23%) versus 16/97 (17%) p=0.04] and mortality [35/315
      (11%) versus 8/97 (8%) p=0.06] compared to those with controlled level (group-1).
      CONCLUSION: A low frequency of diabetics attained the optimal 2-hour postprandial
      blood glucose level. Action should be taken on this crucial issue for the optimal
      management of diabetes.

PMID- 14578980
TI  - Prevalence and characteristics of celiac disease in type I diabetes mellitus in
      Saudi Arabia.
AB  - OBJECTIVE: To examine the prevalence of celiac disease in young patients in the
      Kingdom of Saudi Arabia with type I diabetes mellitus. METHODS: Serum gliadin
      immunoglobulin (Ig) A and reticulin IgA antibody determination was performed in
      123 patients with type I diabetes mellitus attending the pediatric diabetic
      clinic at King Faisal Specialist Hospital and Research Centre, Riyadh, Kingdom of
      Saudi Arabia between 1995 and 1996. RESULTS: Elevated serum gliadin and reticulin
      IgA antibodies were found in the sera of 10 (8.1%) of the 123 diabetic children;
      none had gastrointestinal symptoms. Six of the 10 subjects had jejunal biopsy,
      which showed total villus atrophy. Four subjects did not undergo jejunal biopsy.
      The gender ratio of the biopsy positive is 5 male:1 female. All subjects with IgA
      positive were put on gluten free diet and normalized in a few months. CONCLUSION:
      The maximum prevalence of celiac disease in our population was 8.1% based on
      immunological marker and the minimum was 4.9% based on antibodies and biopsy
      results.

PMID- 14578981
TI  - Treatment of chronic fistula-in-ano using commercial fibrin glue.
AB  - OBJECTIVE: To ascertain the effectiveness of commercially available fibrin glue
      in closing fistulae in ano. METHODS: A prospective nonrandomized trial was
      performed on 19 patients admitted to King Khalid University Hospital (KKUH),
      Riyadh, Kingdom of Saudi Arabia during the period December 2000 to November 2001.
      Two of the patients had multiple fistulae making a total of 21 fistulae. Patients
      were prepared preoperatively and managed postoperatively according to a
      preplanned protocol. The fistulae were injected with fibrin glue after curettage.
      Follow-up visits were scheduled for one week, one month, 3 months, and one year
      later. RESULTS: Nineteen patients received fibrin glue injections for their 21
      fistulae in ano. Three patients were lost to follow up. Fourteen out of 18 (78%)
      fistulae had successful closure. Two of 4 unsuccessful patients reported
      symptomatic improvement in terms of decreased secretions, itching and pain. There
      has been no evidence of incontinence or complications related to the use of
      fibrin glue in this procedure. CONCLUSION: A healing rate of 78% of chronic
      fistula-in-ano by treatment with commercial fibrin glue is promising. However, it
      needs substantiation by increasing the number of patients and prolonging the
      follow up duration. This procedure is easy for the surgeon to learn and perform.
      The procedure avoids complications associated with fistulotomy both for the
      patient and the surgeon.

PMID- 14578982
TI  - The pattern of developmental dysplasia of the hip.
AB  - OBJECTIVE: This study was conducted to enlarge the knowledge of developmental
      dysplasia of the hip (DDH) in the Kingdom of Saudi Arabia (KSA), and to compare
      its presentation among Saudi population to known international figures. METHODS:
      A prospective study of Saudi patients with DDH that presented to King Khalid
      University Hospital, Riyadh, KSA over 5 years starting September 1996. The
      information needed was obtained directly from one or both parents. RESULTS: Six
      hundred Saudi children were included in this study. The diagnosis of DDH was
      delayed in most patients. The results give an impression that parents'
      consanguinity, positive family history, breech deliveries and the use of
      swaddling have direct relation with increased incidence of DDH in the Saudi
      population. CONCLUSION: A national screening program is needed in KSA.
      Furthermore, nationwide studies will help to identify groups at risk and the
      geographical distribution of the disorder.

PMID- 14578983
TI  - Plasma copper and zinc levels in pregnant women in Gaziantep, Turkey.
AB  - OBJECTIVE: Trace elements such as copper and zinc are important factors on the
      health of pregnant women, fetus and embryonic development. Since these elements
      have important influences on health of pregnant women and the growing fetus, this
      study was designed to evaluate the zinc and copper status of pregnant women in
      Gaziantep, Turkey. METHODS: This study was designed as a prevalence study. Twenty
      two health station region were chosen in 13 health centers in the province of
      Gaziantep city in 1999, and copper and zinc levels were examined in 415 pregnant
      women living in these regions. Plasma copper and zinc concentrations were
      determined spectrophotometrically. Analysis of variance and "t" tests were used
      in the statistical analysis of means. RESULTS: In the examination, plasma copper
      and zinc levels were found as 220.67 mg/dl and 124.91 mg/dl. While zinc
      concentrations were not altered significantly throughout gestation, copper levels
      of pregnant women increased significantly as duration of pregnancy progressed.
      CONCLUSION: Plasma copper was higher in all trimesters of gestation when compared
      to normal range of non-pregnant women. The zinc levels of pregnant women were
      mostly within normal range. It decreased significantly in the pregnant women >35
      years of age and in those whose education was literacy and less. Therefore, zinc
      supplementation in pregnant women is recommended in these groups.

PMID- 14578984
TI  - Light and electron microscopic examination of human subungual tissue. Glomus and
      lamellated bodies.
AB  - OBJECTIVE: There is only limited data related to the subungual glomus body. We
      therefore studied the structure of this organ, aiming to obtain further evidence.
      Additionally, we encountered undefined receptor like structures in close
      association with these glomus cells, named them as lamellated bodies and examined
      both of the structures at light and electron microscopic levels. METHODS: This
      study was carried out at the Faculty of Medicine, Hacettepe University, Ankara,
      Turkey, during the time period May 2001 to March 2002. In this study, the
      subungual tissues of 4 patients were examined. RESULTS: Within subungual tissue,
      2 groups of morphologically significant structures were determined by light
      microscopy. The first structure was described as glomus body. It was
      characterized as an encapsulated structure, rich in rounded clear cells filling
      its central compartment. The latter structure having a lamellated appearance was
      described as lamellated body. In the electron microscopic examination, lamellated
      bodies were characterized by central filament rich large cells and surrounding
      cytoplasmic processes of ensheathing cells, some of which were vacuolated. Glomus
      bodies were surrounded by a capsule and centrally located numerous rounded cells
      which reflected the structural features of an active cell. CONCLUSION: The
      lamellated bodies are very unusual structures and they are not found in any other
      part of the body. The structural organization of the ensheathing cells in the
      lamellated bodies greatly resembles many skin associated receptors. Therefore, we
      planned future studies by using immunohistochemistry, to reveal nervous elements
      for structural contribution.

PMID- 14578985
TI  - Mesenteric cystic lymphangioma.
AB  - Abdominal cystic lymphangioma is a very rare congenital tumor of lymphatic
      origin. It usually appears in the pediatric age and frequently presents with non
      specific symptoms and deceptive signs causing, at times, diagnostic dilemmas.
      Ultrasonography and computer tomography imaging are considered the diagnostic
      modalities of choice. Two cases of mesenteric cystic lymphangioma, one presenting
      as perforated appendicitis and the other as recurrent gastritis, are reported.
      Infection in the first and volvulus in the second case is behind the mode of
      presentation. The diagnostic approach and treatment are described, with emphasis
      on the operative tactic applied for upper jejunal resection. A high index of
      suspicion, accuracy and repeated physical examination and, most important, the
      liberal use of ultrasonography in all cases of unclear abdominal illness may
      contribute considerably to a correct diagnosis and decreased morbidity.

PMID- 14578986
TI  - Perforated appendicitis within paraumbilical hernia.
AB  - The appendix is not uncommonly encountered within an external hernial sac.
      However, acute appendicitis in hernia is quite rare. We report a female patient
      who was admitted and operated as a case of incarcerated, strangulated
      paraumbilical hernia and the hernial sac was found to contain part of the greater
      omentum, pus and acutely inflamed, gangrenous appendix, perforated at the tip.
      Appendicectomy and hernial repair were carried out through the same incision.

PMID- 14578987
TI  - Gemella morbillorum endocarditis.
AB  - A case of Gemella morbillorum (G.morbillorum) endocarditis of the mitral valve in
      a patient with previously normal heart valves is reported. The presentation was
      subacute, and the infection was complicated by perforation of the posterior
      mitral leaflet that necessitated valve repair. Gemella morbillorum infections are
      uncommon, and endocarditis is the most common presentation. G.morbillorum
      endocarditis is probably under recognized, and has not been reported from our
      region. The case is described, and problems in the identification of the organism
      are discussed.

PMID- 14578988
TI  - Sextuplets in Oman.
AB  - Use of ovulation inducing agents has increased the incidence of high order
      multifetal gestation. Such pregnancies are associated with increased maternal
      morbidity and poor perinatal outcome especially due to prematurity. Here, we
      report a case of sextuplet pregnancy following ovulation induction with
      gonadotrophins. This is the first reported case of sextuplets from Oman.

PMID- 14578989
TI  - An anomalous artery supplying the right lobe of the liver.

PMID- 14578990
TI  - Non surgical treatment of recurrent or stuttering priapism in sickle cell
      children.

PMID- 14578991
TI  - The effects of cardiac rehabilitation in patients with coronary artery disease.

PMID- 14578992
TI  - Thromboprophylaxis in laparoscopic cholecystectomy.

PMID- 14578993
TI  - An unusual presentation of perforated appendicitis.

PMID- 14578995
TI  - Thrombolytic therapy for acute myocardial infarction.

PMID- 14578996
TI  - Single-unit responses in the auditory cortex of monkeys performing a conditional
      acousticomotor task.
AB  - The general goal of the present study was to assess the response properties to
      tones of single neurons in the auditory cortex (primary auditory area, A1, and
      middle lateral auditory belt, ML) of two macaque monkeys while performing an
      acousticomotor discrimination task requiring a controlled level of attention and
      motivation. For each neuron, an approximation of the frequency receptive field
      (FRF) was first established. Second, based on the FRF, sets of paired tone
      frequencies were defined in which two different tone frequencies had to be
      associated by the monkey, following a trial and error strategy, to a left or a
      right key-press with the left arm. After acquisition of the association, the two
      tones of the pair were presented randomly ("instruction stimulus") and, if the
      monkey touched the correct key, the stimulus was repeated ("confirmation
      stimulus") and a reward was delivered. The majority of units (63%) had a FRF
      formed by multiple peaks, whereas 25% and 12% of units exhibited a simple U
      shaped FRF and a "mosaic" FRF, composed of several separated zones of response,
      respectively. Five principal response patterns were observed: On, Off, On-Off,
      Sustained, and Inhibition. In relation to the acousticomotor association task,
      some auditory cortical neurons (33%) exhibited a different response to the same
      stimulus when presented, in the same trials, as instruction or as confirmation.
      It was also observed that the response to the same instruction stimulus could
      differ when comparing correct trials with erroneous trials (wrong motor
      response). In conclusion, the response properties of auditory cortical neurons in
      behaving monkeys are strongly dependent on the physical parameters of sounds
      (frequency, intensity, etc.) as indicated by FRF characteristics, but a
      substantial influence of the behavioral context and performance may also play an
      important role.

PMID- 14578997
TI  - Grasping the meaning of words.
AB  - Action affordances can be activated by non-target objects in the visual field as
      well as by word labels attached to target objects. These activations have been
      manifested in interference effects of distractors and words on actions. We
      examined whether affordances could be activated implicitly by words representing
      graspable objects that were either large (e.g., APPLE) or small (e.g., GRAPE)
      relative to the target. Subjects first read a word and then grasped a wooden
      block. Interference effects of the words arose in the early portions of the
      grasping movements. Specifically, early in the movement, reading a word
      representing a large object led to a larger grip aperture than reading a word
      representing a small object. This difference diminished as the hand approached
      the target, suggesting on-line correction of the semantic effect. The semantic
      effect and its on-line correction are discussed in the context of ecological
      theories of visual perception, the distinction between movement planning and
      control, and the proximity of language and motor planning systems in the human
      brain.

PMID- 14578998
TI  - fMRI analysis of ankle movement tracking training in subject with stroke.
AB  - This study examined whether ankle-movement tracking training could improve ankle
      function and brain reorganization, evidenced with functional magnetic resonance
      imagery (fMRI), in a single subject with stroke. Test measurements included self
      ratings of functional activities, 15.24 m (50 feet) walk time, ankle range of
      motion, ankle tracking accuracy, and peak dorsiflexion movement during
      dorsiflexion phases of tracking. Cortical activation in the frontal and parietal
      lobes was measured during fMRI with an active voxel count. Additionally, a signal
      intensity index was determined for the gyrus precentralis (GPrC). Training
      consisted of 16 sessions of tracking waveforms on a computer screen with ankle
      motion. Four pretest, four posttest and two follow-up measurements occurred. Data
      were analyzed by visual inspection and by statistical analysis that examined
      whether posttest measurements exceeded the pretest mean by at least two standard
      deviations on at least two consecutive posttest measurements. Posttest results
      showed that the subject's self report of paretic ankle "catches" (failure of toes
      to clear floor during swing phase) during gait were eliminated and that peak
      dorsiflexion movement improved visually but not statistically. Multiple cortical
      areas showed increased voxel count statistically, as did the intensity index for
      GPrC. Follow-up results showed that the ankle "catches", peak dorsiflexion
      movement, and the intensity index remained at the same levels as posttest. Voxel
      counts returned toward pretest values. We concluded that tracking training
      produced training effects in both ankle function and brain reorganization.

PMID- 14578999
TI  - Information processing in long delay memory-guided saccades: further insights
      from TMS.
AB  - The performance of memory-guided saccades with two different delays (3 s and 30 s
      of memorisation) was studied in eight subjects. Single pulse transcranial
      magnetic stimulation (TMS) was applied simultaneously over the left and right
      dorsolateral prefrontal cortex (DLPFC) 1 s after target presentation. In both
      delays, stimulation significantly increased the percentage of error in amplitude
      of memory-guided saccades. Furthermore, the interfering effect of TMS was
      significantly higher in the short delay compared to that of the long delay
      paradigm. The results are discussed in the context of a mixed model of spatial
      working memory control including two components: First, serial information
      processing with a predominant role of the DLPFC during the early period of
      memorisation and, second, parallel information processing, which is independent
      from the DLPFC, operating during longer delays.

PMID- 14579000
TI  - Neural responses in motor cortex and area 7a to real and apparent motion.
AB  - The neural activity in area 7a and the arm area of motor cortex was recorded
      while real or path-guided apparent motion stimuli were presented to behaving
      monkeys in the absence of a motor response. A smooth stimulus motion was produced
      in the real motion condition, whereas in the apparent motion condition five
      stimuli were flashed successively at the vertices of a regular pentagon. The
      stimuli moved along a low contrast circular path with one of five speeds (180-540
      deg/s). We found strong neural responses to real and apparent motion in area 7a
      and motor cortex. In the motor cortex, a substantial population of neurons showed
      a selective response to real moving stimuli in the absence of a motor response.
      This activity was modulated in some cases by the stimulus speed, and some of the
      neurons showed a response during a particular part of the circular trajectory of
      the stimulus; the preferred stimulus angular locations were evenly distributed
      across this neuronal ensemble. It is likely that these neural signals are
      continuously available to the motor cortex in order to generate responses that
      demand immediate action. In area 7a, two overlapping populations of neurons were
      observed. The first comprised cells the activity of which was tuned to the
      angular location of a circularly moving stimulus in the real motion condition.
      These cells also responded to apparent motion at high stimulus speeds. A visual
      receptive field analysis showed that the angular tuning in most of the area 7a
      neurons did not depend on the spatial location of the stimulus in relation to
      their receptive field. The second population was selective to apparent moving
      stimuli and showed a periodic entrainment of activation with the period of the
      inter-stimulus interval of the flashing dots. Both the angular location and the
      inter-stimulus interval neural signals can be used to generate precise behavioral
      responses towards real or apparent moving stimuli.

PMID- 14579001
TI  - Motor planning: effect of directional uncertainty with continuous spatial cues.
AB  - We have investigated the effect of directional uncertainty on the planning of
      reaching movements. For this purpose, we have used sections of annuli as spatial
      cues to indicate the directional range within which the target would be
      presented. The results showed that the reaction time of the reaching response
      increased with cue range and with the angle between the center of the cue and the
      target. In addition, the initial direction of movement was biased toward the
      center of the cue. These results conformed to the predictions of the capacity
      sharing model. This model assumes that the processing resources used for motor
      planning are limited and distributed as a function of the range of directions
      indicated by the cue, and that when the target appears, these resources are
      reallocated to represent the response to be executed.

PMID- 14579002
TI  - Overarm throwing speed in cerebellar subjects: effect of timing of ball release.
AB  - Cerebellar subjects cannot throw fast and show variability in ball speed from
      throw to throw. One possible reason is that they release the ball at times when
      arm speed is not at its maximal value. Therefore, we investigated the hypothesis
      that the slow and variable speeds of throws made by cerebellar subjects are
      caused by their known large variability in the timing of ball release. Eight
      cerebellar subjects and matched controls were instructed to make overarm throws
      fast and accurately. Angular positions of arm segments were recorded with search
      coils at 1,000 Hz. Timing of ball release was measured with respect to the time
      of occurrence of seven arm kinematic reference points. All cerebellar subjects
      showed strong relations between ball speed and the timing of ball release, with
      faster ball speeds associated with late ball release. In agreement, faster ball
      speeds were also associated with longer hand paths to ball release, and with
      balls which went low on the target. However, when timing of ball release was
      optimal for achieving maximal ball speed in the cerebellar subjects, their
      fastest ball speeds were on average only 67% those of controls. Similarly, peak
      forearm angular velocity (one measure of arm speed) in the cerebellar group was
      58% that of the control group. It is concluded that the large variability in
      timing ball release in cerebellar subjects contributes to their variability in
      ball speed, but is only a minor factor in their inability to throw fast. The
      major reason why cerebellar subjects do not throw fast is that they do not
      generate fast arm speeds.

PMID- 14579003
TI  - Lack of neuroprotection by heat shock protein 70 overexpression in a mouse model
      of global cerebral ischemia.
AB  - Heat shock protein 70 (Hsp70) is induced in cells by a variety of stress
      conditions, is known to be cytoprotective, and has been proposed to be
      neuroprotective during brain ischemia. A recently developed mouse model of 12-min
      global cerebral ischemia by bilateral common carotid artery occlusion with
      artificial ventilation and bilateral monitoring of regional cerebral blood flow
      by laser Doppler was applied. We examined the expression and possible
      neuroprotective role of the inducible form of Hsp70 in the mouse brain following
      global cerebral ischemia. Ischemia induced a marked expression of Hsp70 in the
      ischemia vulnerable CA1-CA3 region of the hippocampus. Intraischemic hypothermia
      (33 degrees C) prevented cell damage without noticeable expression of Hsp70. A
      transgenic mouse overexpressing Hsp70 was subjected to 12 min of global cerebral
      ischemia, and the brain damage was evaluated after 4 days. No neuroprotection of
      ischemia-induced brain damage in hippocampus, striatum, cortex or thalamus was
      found in Hsp70 transgenic animals compared with wild-type littermate mice. We
      suggest that overexpression of Hsp70 following cerebral ischemia is an indicator
      of cell stress. Also, constitutively overexpression of Hsp70 is insufficient to
      effectively influence cell death after global cerebral ischemia in the mouse.

PMID- 14579005
TI  - Antiepileptic drugs and cortical excitability: a study with repetitive
      transcranial stimulation.
AB  - Repetitive transcranial magnetic stimulation (rTMS) delivered at various
      intensities and frequencies excites cortical motor areas. Trains of stimuli (at 5
      Hz frequency, and suprathreshold intensity) progressively increase the size of
      muscle evoked potentials (MEPs) and the duration of the cortical silent period
      (CSP) in normal subjects. The aim of this study was to evaluate the effect of the
      antiepileptic drugs carbamazepine, gabapentin, and topiramate on cortical
      excitability variables tested with rTMS. We tested the changes in motor
      threshold, MEP size and CSP duration evoked by focal rTMS in 23 patients with
      neuropathic pain before and after a 1-week course of treatment with
      carbamazepine, gabapentin, topiramate and placebo. None of the three
      antiepileptic drugs changed the resting or active magnetic and electrical motor
      threshold. Antiepileptic treatment, but not placebo, abolished the normal rTMS
      induced facilitation of MEPs, but left the progressive lengthening of the CSP
      during the rTMS train unchanged. Our results suggest that carbamazepine,
      gabapentin and topiramate modulate intracortical excitability by acting
      selectively on excitatory interneurons.

PMID- 14579004
TI  - Interactions between inhibitory and excitatory circuits in the human motor
      cortex.
AB  - Cortical activity depends on the balance between excitatory and inhibitory
      influences. Several different excitatory and inhibitory systems in the human
      motor cortex can be tested by transcranial magnetic stimulation (TMS). While
      considerable information is known about these different inhibitory and excitatory
      phenomena individually, how they are related to each other and how they interact
      is not well understood. Several recent studies have investigated the interactions
      between some of these circuits by applying them together. It has been found that
      short-interval intracortical inhibition (SICI) and long-interval intracortical
      inhibition (LICI) are mediated by different circuits. LICI appears to inhibit
      SICI, which may occur through presynaptic GABA(B) receptors. Interhemispheric
      inhibition elicited by stimulation of the contralateral motor cortex also
      inhibits SICI and may share inhibitory mechanisms with LICI. Long-interval
      afferent inhibition induced by median nerve stimulation inhibits LICI but does
      not interact with SICI. Based on these results, a model of interactions between
      different inhibitory systems that can be tested and refined in the future is
      proposed. Further studies of the interaction between different cortical
      inhibitory and excitatory circuits should improve our understanding of the
      functional organization of the motor cortex and allow better interpretation of
      abnormal findings in disease states. It may also be developed into a new way of
      studying the pathophysiology of diseases and the effects of intervention.

PMID- 14579006
TI  - A step and a hop on the Muller-Lyer: illusion effects on lower-limb movements.
AB  - Past studies have shown that the effects of visual illusions on upper-limb
      movements can be modulated by the availability of current or recent visual
      information. The generality of this finding across body movements was examined by
      measuring the impact of the Muller-Lyer illusion on two types of lower limb
      actions. Subjects stood at one end of a Muller-Lyer figure, then either stepped
      or hopped to the other end. Visual feedback was manipulated through the use of
      visual closed-loop, open-loop, and open-loop three second delay conditions. For
      both stepping and hopping, effects of the illusion on movement accuracy were
      small in the closed-loop, moderate in the open-loop, and large in the three
      second open-loop delay condition. These results were similar to those found in
      studies involving the Muller-Lyer illusion and upper-limb movements. The similar
      effects across different body movements suggests that a common visuomotor system
      subserves both upper and lower-limb movements, and that egocentric and
      allocentric reference frames make similar contributions for the two types of
      movements.

PMID- 14579008
TI  - Cross-modal congruency and visual capture in a visual elevation-discrimination
      task.
AB  - Participants in this experiment were required to discriminate the elevation of
      visual target stimuli (upper versus lower) presented to either side of fixation,
      while simultaneously trying to ignore vibrotactile distracters presented
      independently from the index finger (up) or thumb (lower) of either hand. The
      participants' hands were occluded from view under an opaque screen while the
      visual targets were situated directly over the hands above the screen.
      Participants responded more slowly on this elevation-discrimination task when the
      vibrotactile distracters were incongruent with the elevation of the visual
      targets (i.e. a "lower" vibration to the thumb during the presentation of an
      upper visual target) than when they were congruent (presumably due to the
      competing responses primed by the target and distracter stimuli on incongruent
      trials). The vibrotactile distracters had less of an effect on performance when a
      pair of rubber hands was placed on top of the screen, "holding" the target
      lights, in a posture consistent with that of the participant. Those participants
      who agreed most strongly with a statement about feeling the vibrations at the
      location of the rubber hands in a post-congruency task questionnaire evidenced
      the greatest reduction in the magnitude of the cross-modal congruency effect.

PMID- 14579009
TI  - Recombinant human estrogen, androgen and progesterone receptors for detection of
      potential endocrine disruptors.
AB  - This work reports the binding capacity of various chemicals (so-called endocrine
      disruptors) to recombinant human steroid receptors (hERalpha, hPR and hAR). The
      tested chemicals are organochlorine insecticides (DDT and its metabolites,
      methoxychlor, aldrin, dieldrin, chlordecone, lindane, trichlorobenzene),
      estrogenic insecticides (endosulfan, toxaphene, nonachlor), herbicides (alachlor
      and atrazine), fungicides (benomyl and vinclozolin), industrial chemicals
      (nonylphenol, bisphenol A, diphenylphtalate), antioxidants (butylated
      hydroxyanisol) and some phytoestrogens. Except for phytoestrogens, most of the
      tested chemicals (DDT and its metabolites, aldrin, alpha- and beta-endosulfan,
      toxaphen, trans-nonachlor) show higher affinities for hPR than for hERalpha,
      indicating that the interaction with the progesterone receptor could contribute
      to the endocrine-disrupting effects imputed to these chemicals. We propose to use
      binding assays using recombinant human steroid receptors as screening tools for
      the detection of endocrine disruptors in various samples.

PMID- 14579010
TI  - Determination of trace elements in planktonic microcrustaceans using total
      reflection X-ray fluorescence (TXRF): first results from two Chilean lakes.
AB  - First results are described from the application of a recently developed dry
      method for determination of elements in single specimens of freshwater
      microcrustaceans, using total reflection X-ray fluorescence spectrometry (TXRF).
      This method is a powerful, non-destructive technique for quantifying the trace
      element content of minute biological samples with a dry weight of 3-50 microg.
      Three different freshwater microcrustaceans were sampled, from the natural,
      uncontaminated Lake Laja and from the artificial Rapel reservoir which is
      slightly contaminated by drainage water from a copper mine. Single specimens of
      Daphnia pulex, Bosmina chilensis, and Ceriodaphnia dubia were prepared using a
      modification of the dry method and measured by TXRF. The results showed that both
      As, Mn, Fe, Ni, Zn, and Cu content and the bioaccumulation of these metals were
      usually significantly different between the microcrustaceans from the two lakes.
      The largest difference was found for Cu which was eight times more concentrated
      in the two microcrustaceans from Rapel reservoir than it was in D. pulex from
      Lake Laja.

PMID- 14579011
TI  - Reaction monitoring of enzyme-catalyzed ester cleavage by time-resolved
      fluorescence and electrospray mass spectrometry: method development and
      comparison.
AB  - Two complementary methods for reaction monitoring of the esterase-catalyzed
      cleavage of bis(2-pyridylmethyl)(2-acetoxyphenyl)amine are developed and
      compared. While enzyme-amplified lanthanide luminescence (EALL) allows for the
      time-resolved fluorescence determination of the intrinsically non-fluorescent
      product, both substrate and product of the enzymatic reaction may be determined
      simultaneously by electrospray mass spectrometry (ESI-MS). Excitation wavelength
      for the Tb(III) complex of the reaction product is 297 nm and emission was
      detected at 545 nm, which is the characteristic emission wavelength of the
      terbium(III) ion. In contrast to other EALL techniques, the presented method
      allows for the direct monitoring of an enzymatic conversion without any further
      sample preparation (e.g., rebuffering). For the mass spectrometric measurements
      the mass traces were set to m/z=306, 328, 348, and 370 for the protonated ester,
      the resulting phenol and their sodium adducts, respectively.

PMID- 14579012
TI  - Highly parallel dispensing of chemical and biological reagents.
AB  - We present a technology for the highly parallel dispensing of a multitude of
      reagents. It allows one to dispense up to 96 different reagents simultaneously in
      a fixed array, in a volume range of 100 pL up to several nL. The pitch of the
      dispensed droplets can be as small as 500 microm. All channels are fired
      simultaneously, giving an unprecedented throughput. The system was originally
      developed for the high-throughput fabrication of microarrays, but can easily be
      adopted for other applications such as highly parallel filling of
      nanotiterplates. Based on our standard configuration we achieved droplets with
      125- micro m in-flight diameter (1.2 nL) with a CV of <1%.

PMID- 14579014
TI  - [If it becomes too narrow for the spinal cord--plea for a joint venture].

PMID- 14579015
TI  - [Attachment points of the posterior longitudinal ligament and their importance
      for thoracic and lumbar spine fractures].
AB  - Spine fractures with damage of the posterior wall of the vertebra often can be
      anatomically reconstructed by indirect reduction. Whether the posterior
      longitudinal ligament (PLL) is responsible for the reduction is still subject to
      debate. The aim of our investigation was to ascertain the role of the PLL in
      closed reduction of spine fractures by identifying the bony attachment points of
      this ligament. We performed a gross anatomical dissection, a light- and polarized
      microscopic investigation on 22 human cadaverous thoracic and lumbar spines to
      determine the points of attachment of the PLL. We found two layers of the PLL.
      The superficial layer runs from the first thoracic down to the third lumbar
      vertebra with a width of 0.4-1.0 cm and from there descends as a thin rudiment to
      the sacrum. The deep layer shows a segmental rhomboid structure. Lateral fibers
      are attached to the annulus fibrosus and at the rim of the adjacent vertebrae.
      Medial fibers are attached additionally to the posterior wall of the vertebral
      bodies by bridging the foramina basivertebralia. Since these foramina become
      enlarged in the caudal parts of the vertebral column, the number of attachment
      points at the posterior wall of the vertebral bodies decreases caudally. Good
      results for reconstruction of the posterior wall in vertebral fractures of the
      thoracic and upper lumbar spine can be explained by the anatomical situation of
      the PLL and stress the important role of the PLL in indirect reduction of spine
      fractures.

PMID- 14579013
TI  - Pharmacogenetics of paraoxonases: a brief review.
AB  - The human paraoxonase (PON) gene family consists of three members, PON1, PON2,
      and PON3, aligned next to each other on chromosome 7. By far the most-studied
      member of the family is the serum paraoxonase 1 (PON1), a high-density
      lipoprotein-associated esterase/lactonase. Early research focused on its
      capability to hydrolyze toxic organophosphates, and its name derives from one of
      its most commonly used in vitro substrates, paraoxon. Studies in the last 2
      decades have demonstrated PON1's ability to protect against atherosclerosis by
      hydrolyzing specific derivatives of oxidized cholesterol and/or phospholipids in
      oxidized low-density lipoprotein and in atherosclerotic lesions. Levels and
      genetic variability of PON1 influence sensitivity to specific insecticides and
      nerve agents, as well as the risk of cardiovascular disease. More recently, the
      other two members of the PON family, PON2 and PON3, have also been shown to have
      antioxidant properties. A major goal in present research on the paraoxonases is
      to identify their natural substrates and to elucidate the mechanism(s) of their
      catalytic activities.

PMID- 14579016
TI  - [Laser-evoked potentials: diagnostic approach to the dorsal root].
AB  - Functional diagnostics of the dorsal root are especially effective via
      nociceptive fibers on account of less intersegmental overlap compared to large
      diameter fibers of the mechanoreceptive afferents. Laser-evoked potentials (LEP)
      are induced by short, painful heat stimuli. The aim of this work was to describe
      changes of the LEP in cases of dorsal root damage. The recorded LEP changes will
      be discussed with regard to their prognostic value as well as pathophysiologic
      aspects of dorsal root damage. Dorsal root function was tested in 21 patients
      suffering from clinically proven radiculopathy in one of the segments L4 to S1.
      Mechanosensibility and thermosensibility were clinically investigated. LEP were
      induced by slightly painful stimuli (80 on the affected and 80 on the
      contralateral unaffected dermatome). The LEP were evaluated by amplitude of the
      averaged electroencephalogram (EEG). In addition, a subjective pain rating was
      recorded after each stimulus. Investigation of dorsal root function by LEP in
      patients with radiculopathy yields two typical changes of the amplitude. On the
      one hand, there were significant reductions of amplitude, and on the other hand,
      a complete loss of LEP was found. LEP changes allow a graduation of patients who
      show no obvious differences in their clinical appearance. Which mechanisms are
      responsible as concerns deafferentiation and neuropathy of the dorsal root fibers
      are discussed. With regard to the LEP changes, a prognostic relevance in patients
      with dorsal root affections is likely. This question will be addressed in a
      prospective study soon.

PMID- 14579017
TI  - [Importance of the cross-sectional area of the spinal canal in thoracolumbar and
      lumbar fractures. Is there any correlation between the degree of stenosis and
      neurological deficit?].
AB  - A relationship between traumatic spinal canal stenosis and the degree of
      neurological deficit is known for the cervical spine. However, this has not been
      proven for the thoracolumbar and lumbar spine. During a period of 4 years, from
      1996 to 1999, 1168 patients with a spinal injury were treated at our department,
      473 of these by operation. Thirty-five were examined in a separate group. They
      showed a single fracture of the thoracolumbar and lumbar spine with stenosis of
      the spinal canal. All fractures were single burst fractures after blunt trauma.
      All patients were conscious and fully oriented at the time of admission and a
      thorough neurological examination could be performed. The fractures were
      diagnosed by conventional X-ray in two views and computed tomography (CT). Using
      the transverse CT scans in horizontal view, the sagittal diameter was measured
      and the degree of stenosis calculated in percent at the level of the fracture and
      one below and above. The group included 25 male and 10 female patients, with a
      mean age of 38 years (range: 17-61 years). Of the 35 patients, 19 (54.3%) showed
      neurological deficits after spinal cord injury,and 16 (45.7%) were without any
      neurological complications at the time of first admission to the hospital. There
      was no correlation between the extent of spinal canal stenosis and the degree of
      the neurological deficit. One patient with stenosis of 20% suffered from
      neurological dysfunction, others with stenosis up to 80% were without spinal cord
      injury. The average stenosis of the spinal canal was 49.6% in cases with cord
      injury and 46.3% in patients without neurological dysfunction. No correlation and
      no predisposing anatomical structures could be found between stenosis and
      neurological deficit.

PMID- 14579018
TI  - [Physical therapy to treat spinal stenosis].
AB  - Spinal stenosis mainly is a disease of the elderly. In most cases the lumbar
      spine is affected. The assessment is based on the typical constellation of
      symptoms (neurogenic claudication, subjective weakness) and physical findings
      (abnormal reflex status, loss of strength, sensory deficits, impairment in
      balance and coordination). The diagnosis is further supported by the radiologic
      proof of a stenosis of the spinal canal, the lateral recess, and the
      intervertebral foramina. The main targets of physical and rehabilitative medicine
      are the relief of pain and an improvement in the activities of daily living,
      which are especially impaired by reduced walking distance and difficulties in
      climbing stairs. These can be achieved by multimodal, conservative management:
      physiotherapy, occupational therapy, treatment of myofascial disorders, and oral
      medication/local injections. Physiotherapy aims at a stabilization of the lumbar
      spine in a flexed posture rather than in lumbar lordosis and at an increase of
      overall physical fitness. Oral analgetic and/or anti-inflammatory medical
      management is based on the three-step scheme of the World Health Organization,
      which also can be applied for low back pain. Local injections can help to control
      symptoms. Myofascial disorders are treated by techniques and procedures such as
      traditional massage.

PMID- 14579020
TI  - [Surgical treatment of spinal stenosis].
AB  - Surgical treatment of lumbar spinal stenosis is aimed at decompressing the
      structures of the spinal canal. Several surgical techniques have been described
      over the last few years. This article gives a survey of the surgical procedures
      used for the treatment of spinal stenosis. When comparing and discussing
      indications and current surgical techniques used for spinal stenosis, one can
      describe some general tendencies: if the symptoms are severe or disabling and do
      not respond to appropriate conservative treatment, or if the patient is not able
      to cope with the pain any longer and views his or her quality of life as
      unacceptable, surgery is indicated. If the symptoms are mainly radicular,
      (microsurgical) decompression should be performed. If back pain is the main
      problem combined with preoperative evidence of segmental instability,
      spondylolisthesis, or scoliosis, one should consider spinal fusion in addition to
      an appropriate decompression. Further investigations are necessary to exactly
      find out the appropriate indications for a fusion and to answer the question of
      whether spinal instrumentation should be used.

PMID- 14579019
TI  - [Minimally invasive percutaneous epidural neurolysis in chronic radiculopathy. A
      prospective controlled pilot study to prove effectiveness].
AB  - The treatment of chronic back pain with sciatica is still an unsolved therapeutic
      challenge. Percutaneous minimally invasive neurolysis according to the Racz
      technique is increasingly applied and discussed controversially. So far there is
      no prospective randomized controlled study for evaluation of a possible treatment
      effect. In a prospective pilot study, 25 patients with monosegmental
      radiculopathy of the lumbar spine were treated with minimally invasive
      percutaneous epidural neurolysis according to Racz's technique. They all suffered
      from chronic disc herniations or failed back syndromes after surgery, all with
      radiculopathy. The average age of the patients was 51+/-16 years, the average
      duration of the symptoms was 28 months. Twelve weeks after the procedure patients
      had significant clinical improvement. The Oswestry score increased from 64+/-17
      to 22+/-12 points. Subjective pain sensation according to the McNab score showed
      improvement too. None of the patients had worsening of the situation compared to
      preoperative findings. No clinically relevant complications were observed. The
      results are being used to design a clinical trial in accordance with good
      clinical practice guidelines to analyze the therapeutic efficacy of the
      procedure. The described technique is still a clinically experimental procedure.
      However, due to a low probability of side effects and due to the good results
      reported so far by most authors, the Racz catheter technique may be applied in
      certain patients with chronic radiculopathy refractory to conservative treatment.

PMID- 14579021
TI  - [Microsurgery of acquired degenerative lumbar spinal stenosis. Bilateral over-the
      top decompression through unilateral approach].
AB  - Degenerative lumbar spinal stenosis is diagnosed with an increasing incidence.
      Clinical and radiological signs of progression often result in a significant
      decrease in the patient's quality of life. The indication for surgical treatment
      follows the spectrum of clinical symptoms. In cases with "structural" spinal
      stenosis and predominant "leg symptoms" such as neurogenic claudication and/or
      radicular symptoms, decompressive types of surgery are indicated. However, due to
      the multimorbidity of the mostly elderly patients, the surgical risk should be as
      low as possible whereas the surgical efficacy should be as high as possible. We
      describe a microsurgical technique, which can achieve a bilateral decompression
      of the central and lateral lumbar spinal canal through a unilateral surgical
      approach. In a consecutive series of 275 patients, a significant increase in
      standing time and walking distance could be attained. The surgical complication
      rate was low. A complete decompression of the spinal canal with preservation of
      the "tension band" of the posterior spinal column could be achieved. Although
      this type of surgery is adequate for patients with "predominantly leg symptoms"
      only, low back pain improved as well in nearly 50% of the patients. However, in
      cases with dynamic spinal stenosis and/or disturbed curvature with predominant
      low back pain, a combination of the described procedure with stabilizing surgery
      (spinal fusion, dynamic fixation etc.) is recommended.

PMID- 14579023
TI  - [Traumatological reflection on the narrow spinal canal. Review and our own
      concept].
AB  - Even today, injuries of the spinal column still pose a large challenge for the
      treating trauma surgeons. In the last century due to more differentiated
      diagnostics, the concept of predominantly conservative treatment changed to
      interventional procedures especially in the so-called unstable injuries.
      Discrepancies still exist in the evaluation of stability. In the last few years,
      dorsal, ventral, or combined interventional procedures have become established.
      The narrow spinal canal and neurological deficits represent important factors.
      Based on the literature, the different procedures and evaluations are discussed
      and finally we introduce our own concept.

PMID- 14579024
TI  - [Possible conservative treatment methods for patients with spinal claudication].
AB  - The success of multimodal therapy for patients with symptoms of spinal canal
      stenosis lasting >6 months was investigated in a prospective study. Clinical
      (age, weight, height) and morphological data were collected for 36 patients (21
      women and 15 men) with an average age of 67 years. The extent of narrowing in the
      spinal space (diameter of the dural sac <100 mm(2)) was measured by magnetic
      resonance imaging at segments L1-S1. Impairments in daily activities were
      assessed by questionnaire before a 3-week multimodal treatment regimen and 3
      weeks and 6 months thereafter. In addition, depression status and walking
      distance on a treadmill were evaluated. Of the 180 segments examined, 124
      evidenced a diameter of the dural sac of <100 mm(2). The average functional
      capacity improved with treatment from 46.7 to 53.5 (p<0.001) and the average
      depression status decreased from 13.5 to 11 (p>0.05). The average walking
      distance was 373 m before treatment and 565 m after treatment (p<0.001). Short
      term improvement of the walking distance was achieved with the conservative
      treatment implemented. Medium- and long-term results remain unclear. Predictors
      for treatment success (age, sex, BMI, functional capacity, walking ability before
      treatment) could not be found. No scientific evidence can be gleaned from the
      literature in this regard so that further prospective studies should be
      performed.

PMID- 14579025
TI  - [Bilateral vertebral artery dissection after chiropractic treatment].
AB  - A 31-year-old woman suffered a brainstem infarction secondary to chiropractic
      neck manipulation. A dissection of both vertebral arteries could be demonstrated
      by MR tomography. This case report should alert therapists to be aware of
      vertebrobasilar complications after spinal manipulations.

PMID- 14579027
TI  - [Funnel chest. New aspects since introduction of a minimally invasive surgical
      technique].
AB  - For many years, a variety of open surgery techniques represented the "golden
      standard" for remodeling the chest wall of patients with pectus excavatum. This
      situation changed when a minimally invasive approach was first introduced by D.
      Nuss (minimally invasive repair of pectus excavatum--MIRPE). This procedure was
      originally developed only for children and is based on the fact that the growing
      chest wall is still flexible. The indication for MIRPE is identical for both open
      surgery and the minimally invasive procedure. The new technique is gaining
      acceptance worldwide in the field of pediatric surgery, and older patients who
      resist open surgery for correction of their pectus excavatum now request the new
      and less invasive procedure. Most of them found their information via the
      Internet and it is noteworthy that patients, or their parents, are now looking
      differently at the indication for repairing pectus excavatum.

PMID- 14579028
TI  - [Treatment of knee joint arthritis in the middle-aged patient].
AB  - Degenerative arthritis of the knee joint is a common problem of the middle-aged
      patient. Primary arthritis has to be distinguished from secondary disease caused
      by malalignment, instability or trauma. The key symptom is pain at the jointline
      on weight-bearing. Diagnosis is established from history, clinical and
      radiological examination. Treatment options are chosen depending on the severity
      of symptoms and the demands of the patient. They range from modification of
      sports- and recreational activities, nonoperative therapy to operative options
      such as resecting arthroscopic procedures, repair of damaged articular cartilage,
      osteotomy and unicompartmental knee arthroplasty. However, the patient has to be
      made aware that a cure for this disease remains to be found.

PMID- 14579029
TI  - MAP kinases and mTOR mediate insulin-induced phosphorylation of insulin receptor
      substrate-1 on serine residues 307, 612 and 632.
AB  - AIM/HYPOTHESIS: Insulin-induced IRS-1 serine phosphorylation could be
      physiologically important to regulate insulin action. In a hyperinsulinaemic
      state such as obesity or Type 2 diabetes, this phosphorylation could be modified
      and exacerbate insulin resistance. We aimed at identifying serine residues in IRS
      1 phosphorylated in response to insulin stimulation and at determining the
      involved kinases. METHODS: 3T3-L1 adipocytes, muscle and adipose tissue of mice
      were subjected to Western Blot analysis with phosphospecific antibodies to
      identify phosphorylation sites in IRS-1 following insulin treatment.
      Pharmacological inhibitors were used to determine the serine kinases involved in
      this phosphorylation. RESULTS: In 3T3-L1 adipocytes, insulin promoted the
      phosphorylation of serine 307, 612 and 632 with Serine(612/632) more rapidly
      phosphorylated than Serine(307). Insulin-induced phosphorylation of Serine(307)
      was dependent on the activation of a PI 3-kinase/mTOR pathway. The
      phosphorylation of Serine(612/632) required the activation of the MAP kinase
      pathway following short-term insulin stimulation and activation of the PI 3
      kinase/mTOR pathway following prolonged insulin stimulation. Phosphorylation of
      Serine(307) and Serine(632) occurred in vivo in skeletal muscle and white adipose
      tissue of mice injected with insulin and was dependent on the activation of mTOR.
      Moreover, inhibition of mTOR led to a persistent PI 3-kinase activation by
      insulin. CONCLUSION/INTERPRETATION: Insulin-induced IRS-1 serine phosphorylation
      is a complex process involving different sites and kinases. This complexity could
      be physiologically important to accurately regulate insulin signalling. Abnormal
      phosphorylation of these serine residues in hyperinsulinaemic state could
      participate in the down-regulation of insulin signalling.

PMID- 14579030
TI  - [New biological therapeutic options for the treatment of RE: inhibition of
      costimulatory molecules and blockade of Interleukin-6-interaction].
AB  - After approval of TNF and interleukin-1 inhibiting agents for treatment of
      refractory rheumathoid arthritis, new agents inhibiting interleukin-6 and
      costimulatory pathways are entering clinical phase I and II trials. Blockade of
      costimulation by using a CTLA4 immunoglobulin fusion protein (CTLA4Ig), which
      inhibits the interaction between CD 28 and CD80/86, has been studied in humans
      and was demonstrated to be well tolerated and efficacious. A monoclonal antibody
      to the IL-6 receptor (MRA) blocks bioactivity of IL-6 and also showed favorable
      effects in first clinical trials. Drug safety data on both substances revealed no
      severe toxicity or increased incidence of severe infections. For the first time
      combinations of biological substances like CTLA4Ig and etanercept were
      demonstrated to be effective and showed no evidence for an increased rate of
      severe infectious complications. Encouraged by data on these two agents there is
      substancial hope for a broadened therapeutic armentarium of biological agents in
      refractory rheumatoid arthritis.

PMID- 14579031
TI  - [Use of biologicals in psoriasis].
AB  - With a prevalence of 2-3 percent, psoriasis is one of the most common diseases in
      dermatology. Most patients can be treated sufficiently with topical emollients,
      but approximately 20 percent of all patients suffering from psoriasis need photo-
      and/or systemic therapies. Side effects, contraindications, insufficient clinical
      responses, and lack of long-term efficacy underline the need for novel and
      improved antipsoriatic therapies. Several biologics interfering with key steps in
      the immunopathogenesis of psoriasis bear the potential to meet this need with
      regard to treating moderate to severe psoriasis. Progress made in the
      understanding of the pathophysiology of psoriasis as T-cell mediated dermatosis
      does provide options for new, more precise therapeutic approaches. These
      immunological therapeutic strategies are targeted at the inhibition of T-cell
      activation, the depletion of activated T-lymphocytes, the inhibition of adhesion
      of inflammatory cells, the inhibition of effects of proinflammatory cytokines and
      the application of antiinflammatory cytokines. This article gives a summary of
      new biologicals used in the treatment of psoriasis. Clinical results received
      from first applications are inconclusive. Further results of the studies from
      phase II and phase III can be expected in the next few years, which should make
      it possible to achieve better assessments of the potential of these types of
      treatments. Some of these approaches could lead to the approval of new drugs to
      treat psoriasis and to enhance or replace already existing therapeutic options.

PMID- 14579032
TI  - [Epidemiology and therapy of Lyme arthritis and other manifestations of Lyme
      borreliosis in Germany: results of a nation-wide survey].
AB  - AIM OF THE STUDY: Only little is known about the epidemiology of Lyme borreliosis
      in Germany. As an example, it is still unclear if there are regional differences
      in the incidence of Lyme disease in general or of certain clinical manifestations
      like Lyme arthritis. Moreover, standardization of diagnostic or therapeutic
      procedures does not exist. Therefore, a Germany-wide questionnaire-based survey
      was conducted in order to achieve more epidemiological data and to obtain more
      information about the diagnostic and therapeutic approaches of general
      practitioners and specialists. METHODS: A self-designed questionnaire was
      distributed along with two editions of the journal "Deutsches Arzteblatt" (which
      is delivered to every physician in Germany) and additionally by a pharmaceutical
      company. During the collection period from March 1, 1998 to February 28, 1999,
      patients with Lyme disease were reported and information was given about site of
      infection, diagnostic procedures, clinical symptoms, treatment, and outcome.
      RESULTS: Altogether 3935 patients were reported. Their mean age was 43.4 years
      with the peak incidences around the ages of 10 and 60 years. 37.3% of the
      questionnaires were sent in by general practitioners, 17.6% by dermatologists,
      15.7% by pediatricians, 9.7% by internists, and 2.7% by neurologists. 83% of the
      patients did not have a special infecion risk. The most frequent clinical Lyme
      manifestation was erythema migrans (EM), which occurred in 50.9% of the patients.
      21.3% suffered from general symptoms. Of special interest, 24.5% of the patients
      had Lyme arthritis (14.7% mon- or oligoarthritis, 9.8% polyarthritis). Therefore,
      arthritis was more frequently reported than neuroborreliosis (18.4%). Only 16% of
      the neuroborreliosis patients and 32% of the arthritis patients remembered having
      had an EM. 189 patients (4.8%) with lymphadenosis cutis benigna and 100 patients
      (2.5%) with acrodermatitis chronica atrophicans were reported. In 80.4% of the
      patients, positive Lyme serology was detected. In a few cases, the diagnosis was
      established by isolation of borreliae, PCR or histology. 3754 patients were
      treated by antibiotics. The most frequently used compounds were doxycycline
      (50.4%), followed by ceftriaxone (22.4%), amoxicillin (13.6%), penicillin (7%),
      and erythromycin (4.2%) with differences depending on clinical manifestations and
      specialization of the prescribing physician. In less than 10% of the cases, not
      evaluated or recommended therapeutic procedures were performed. DISCUSSION: Lyme
      disease is endemic throughuot Germany. The most frequent manifestations are EM,
      followed by Lyme arthritis and neuroborreliosis. Less than one third of patients
      suffering from disseminated or chronic Lyme disease remembered an EM. Most of the
      physicians taking part in this survey follow treatment recommendations concerning
      choice of antibiotics and treatment durations.

PMID- 14579033
TI  - [Collagen breakdown in ankylosing spondylitis-relationship to disease related
      parameters].
AB  - OBJECTIVE: Patients with ankylosing spondylitis (AS) often develop osteoporosis
      particularly of the axis skeleton. To investigate disease-related or therapeutic
      influence on bone catabolism, we quantified the total excretion of the collagen
      crosslinks (CL) pyridinoline (Pyd) and deoxypyridinoline (Dpyd) in 91 AS patients
      (26 f, 65 m) in relation to disease activity or stage and therapy with NSAID.
      METHODS: CL were determined by HPLC (High Performance Liquid Chromatography).
      RESULTS: The AS patients show a highly significant positive correlation between
      Pyd and the inflammatory activity (CrP, r = 0.36, p < 0.001: ESR, r = 0.379, p <
      0.001). Also the quotient Pyd/Dpyd correlates positively to the inflammatory
      activity (CrP, r = 0.262, p < 0.001: ESR, r = 0.325, p < 0.002). In the case of
      increased inflammatory disease activity (CrP > or = 10 mg/l vs CrP < 10 mg/l or
      ESR > or = 10 30 mm vs ESR < 30 mm), Pyd excretion is raised significantly (p <
      0.042 for CrP and p < 0.009 for ESR). Among those patients treated with NSAID
      therapy, significantly reduced levels for Dpyd (p < 0.001) and raised levels for
      the quotient Pyd/Dpyd (p < 0.002) appear. In the case of advanced radiological
      changes with evidence of syndesmophytes, Pyd (p = 0.014) and Dpyd (p < 0.004)
      were significantly raised in urine. Regarding the movement function (finger-floor
      distance, schober test), no significant correlation to crosslink excretion could
      be proven. CONCLUSION: From our investigations, we assume that osteoporosis in AS
      is primarily caused by an inflammatory-mediated degradation of bone.

PMID- 14579034
TI  - [Sauve-Kapandji procedure in destructive monarthritis of the distal radioulnar
      joint].
AB  - INTRODUCTION: Detructive monarthritis of the distal radioulnar joint (DRUJ) is
      rare. PATIENTS AND METHODS: Three patients with destructive monarthritis of the
      DRUJ were treated by arthrodesis in the technique described by L. Sauve and M.
      Kapandji, modified by I. A. Kapandji. Prospective evaluation with a mean follow
      up of 12 months was performed. RESULTS: After cast immobilization for 3 weeks and
      mobilization, bone healing was uneventful. All patients were completely free of
      pain. Even a painless "snap" at the end of the ulna was mentioned in all, if
      rotating the forearm with powerful grasp. Rotation of the forearm improved
      completely. Wrist motion also improved after arthrodesis of DRUJ but did not
      reach the range of motion of the unaffected hand. Irritation of the ramus
      dorsalis nervi ulnaris was found in one patient 9.5 months after arthrodesis and
      disappeared after removal of the screws. CONCLUSION: Arthrodesis of the DRUJ with
      distal segmental resection of the ulna seams to be an effective therapy for
      destructive monarthritis of the DRUJ after failed non-operative and joint
      preserving operative treatment.

PMID- 14579035
TI  - [Toxic epidermal necrolysis induced by NSAID].

PMID- 14579036
TI  - [Imaging techniques in rheumatology: scintigraphy in rheumatoid arthritis].
AB  - Bone scintigraphy is an important tool for staging and follow-up in patients with
      rheumatoid arthritis, and is part of the training for board certified physicians
      in nuclear medicine in Germany. Bone scintigraphy uses the accumulation of i.v.
      injected technetium-99m labeled phosphonates imaged with a gamma camera.
      Different phases can be defined: perfusion phase (0-60 s p. i.), blood pool phase
      (2-5 min p. i.), and bone (turnover) phase (2-5 h p. i.). The blood pool phase
      allowes judgement of inflammatory (soft tissue) components of joint disease
      ("arthritis"), the bone (turnover) phase of longer lasting bone processes
      ("arthrosis"). The technical details including documentation of the scintigraphic
      results are presented according to the procedure guidelines of the German Society
      of Nuclear Medicine (www.nuklearmedizin. de).

PMID- 14579037
TI  - [Interdisciplinary rheumatology: State of the Art in Vasculitis Summer Academy
      04/05 July 2003, Bad Bramstedt].

PMID- 14579038
TI  - [Think clearly, be sincere, act calmly: Adolf Kussmaul (1822-1902) un his
      significance for medicine in the 21st century].

PMID- 14579039
TI  - Vitamin E for rheumatoid arthritis or osteoarthritis: low evidence of
      effectiveness.

PMID- 14579040
TI  - [Osteoporosis of ankylosing spondylitis in relation to type of disease course].

PMID- 14579044
TI  - [Peripartum cardiomyopathy-the (un)known obstetricalcardiologic emergency
      situation].
AB  - Peripartum cardiomyopathy (PPCM) is rare cardiac complication afflicting women
      during pregnancy or until 5 months post partum with the typical signs of acute
      cardiac failure. PPCM is similar to dilated cardiomyopathy (DCM) in terms of
      symptoms, histopathology and treatment but is characterized by a better outcome
      with a high rate of spontaneous normalization of left-ventricular size and
      function. The understanding of the etiology is limited. However, viral
      myocarditis and autoimmune factors might be involved in the development of PPCM.
      Clinically, PPCM shows pulmonary symptoms such as dyspnea, tachypnea and
      coughing. The diagnosis is finally established by echocardiography. It has to be
      assumed that PPCM is often undetected or misdiagnosed because of the low
      incidence, the unspecific symptoms and the fact that other pregnancy-related
      factors have similar clinical appearance. The treatment is also unspecific and
      similar to DCM and acute cardiac failure. The severity of the disease requires an
      interdisciplinary approach in a perinatal center with consequent follow-up of the
      patients for risk stratification including echocardiography.

PMID- 14579045
TI  - Angina intensity is not different in diabetic and non-diabetic patients with
      acute myocardial infarction.
AB  - BACKGROUND: Diabetic patients with acute myocardial infarction (AMI) may have
      diminished pain or a higher frequency of asymptomatic infarctions. This appears
      to be a common clinical perception. METHODS: Data from two registries of AMI
      patients presenting in hospital (MITRA PLUS with 18786 patients; North German
      Registry, NGR, 1042 patients with detailed symptom interviews) were analyzed
      concerning symptoms of acute myocardial infarction in patients with diabetes
      mellitus (DM) and without diabetes (non-DM). RESULTS: DM patients were
      significantly older and more often female than non-DM. There were no differences
      in the frequency of pre-infarction angina between DM and non-DM (Mitra Plus). In
      NGR, severe angina during AMI occurred in 49.8% of DM and 46.3% of non-DM (n.
      s.). No chest pain was reported in 16.9% of DM and 15.0% of non-DM (n. s.). Extra
      thoracic pain, dizziness, nausea, sweating, palpitations, radiation of angina and
      localization of radiating pain was not different between DM and non-DM patients.
      Severe dyspnea occurred in 29.5% of DM and 19.5% of non-DM patients (p = 0.003).
      CONCLUSIONS: Apart from a higher frequency of severe dyspnea in diabetics, there
      appears to be no difference in the clinical symptoms of AMI patients with and
      without diabetes mellitus. AMI with little or no angina was also frequently found
      in non-diabetics. In the hospital, diabetics with suspected AMI do not appear to
      need a special judgement of symptoms. This could accelerate access of diabetics
      to standard therapeutic procedures.

PMID- 14579046
TI  - Long-term evaluation of paclitaxel-coated stents for treatment of native coronary
      lesions. First results of both the clinical and angiographic 18 month follow-up
      of TAXUS I.
AB  - The development of restenoses due to tissue proliferation within the stented
      segment is a major limitation of conventional stent implantations. Recently
      published studies have shown that drug-eluting stents effectively decrease the
      incidence of stent restenosis at 6 month follow-up as compared to bare metal
      stents. However, a persistent efficacy of this stent design beyond the 6 month
      period still needs to be proven. Therefore, in this study, we are demonstrating
      the first 18 month follow-up results of a Paclitaxel-coated coronary stent, based
      on the patient population of the TAXUS I study, a multicenter randomized study to
      evaluate both safety and efficacy of the Paclitaxel-coated NIRx stent as compared
      to an uncoated, bare metal stent. In this study we evaluated the long-term
      outcome of NIRx patients of our center, in which 20 out of 31 patients of the
      TAXUS I study with NIRx stent implantation have been enrolled. A clinical follow
      up was available in 20 out of 20 patients (100%) 535 +/- 82 days post stent
      implantation (17.8 months). An angiographic follow-up was available in 14 out of
      20 patients (70%) 580 +/- 77 days post stent implantation (19.1 months). The MACE
      rate at 18 month follow-up was 0.0%. There was no stent restenosis in the study
      group up to 18 month post drug-eluting stent implantation. There was one non
      clinically driven target vessel revascularization due to a stent edge lumen
      renarrowing, which was subsequently calculated as a 43% diameter stenosis.
      Accordingly, this event was not regarded as MACE. The IVUS analysis of the study
      population has shown a decrease of the mean minimum lumen area from 8.45 mm(2)
      postinterventional to 6.87 mm(2) at 6 month follow-up with a relative mean
      maximum plaque area of 16%. At 18 month follow-up, there were no additional
      significant changes with a mean minimum lumen area of 7.16 mm(2) and a relative
      mean maximum plaque area of 13.4%. The reported results of the 18 month follow-up
      of TAXUS I are the first experiences demonstrating a persistent benefit of the
      Paclitaxel-coated NIRx stent. Therefore, this stent design seems to be safe and
      effective, even in long-term follow-up.

PMID- 14579047
TI  - [Surgical therapy of traumatic cardiologic intervention].
AB  - Coronary perforation and entrapment of catheter materials are rare, but life
      threatening complications, which often require emergency cardiosurgical
      treatment. Surgical options include tamponade drainage, coronary artery bypass
      grafting, perforation suturing, and removal of catheter materials. Surgical
      strategies are not standardized but mainly depend on the surgical anatomy. This
      is in particular true for the removal of the catheter remnants (stent,
      guidewire). Keeping this in mind, these patients can be treated with good
      clinical results.

PMID- 14579048
TI  - [Cardiovascular diseases and the subspecialties cardiology and angiology in
      "Schlichtungs"- Proceedings].
AB  - A: The Schlichtungsstelle (expert panel for alternative dispute resolution) of
      Northern Germany, in 2001, decided on 2620 malpractice claims; 233 of these were
      related to the treatment of cardiovascular disorders, coronary and venous
      diseases being the most common. The physicians involved in these disputes
      represented 18 (sub-)specialities. Complaints related to procedures were the ones
      most frequently submitted by the patients, followed by those concerning
      diagnostics. Negligence was found to be present in 37% of the cases, the highest
      proportion being due to mistakes of diagnosis, followed by organisational and
      system-related mistakes. Medical negligence as the cause of injury was assumed in
      46/233 (20%) of the cases, the injuries being serious in 18 and fatal in 6 of the
      46 patients. Negligent and non-negligent iatrogenic injuries combined, amounted
      to 132/233 (57%) of the "cardiovascular" panel cases. B: From 1992 to 2001, we
      collected 165 panel cases involving cardiologists and 3 involving angiologists.
      In most of these the underlying disease was coronary, but in 14 cases the
      underlying disorder was psychosomatic. 35% of the complaints submittted by the
      patients were about invasive procedures. 12% of the instances of negligence
      determined in the panel proceedings were due to procedural mistakes, whereas 47%
      were due to mistakes related to indication and to the monitoring of the patients
      after procedures. Negligent iatrogenic injury was assumed in 27%, non-negligent
      iatrogenic injury in another 53% of the cases, so that the total of iatrogenic
      injuries amounted to 80% of the "cardio-angiologists" panel cases. 19/168 (11%)
      patients died from iatrogenic injuries. Organization and coordination among
      medical persons and institutions treating patients need improvement. A
      considerable number of disputes and claims seems to be initiated and caused by
      deficits in doctor-patient-communication. Attempts at reducing negligence and
      adverse events should center around those professionals actually involved in
      patient care, where the decisions on diagnostics, indication and therapy are
      made. Processes promoting patient safety should be based and depend on the groups
      cooperating in their daily work (department, practice). External influences and
      directives tend to be less effective.

PMID- 14579049
TI  - Small differences in non-fatal in-hospital reinfarctions complicating acute
      myocardial infarction as observed in current randomised controlled trials will
      not essentially influence long-term mortality. Results from the Maximal
      Individual Therapy in Acute Myocardial Infarction (MITRA) Registry.
AB  - BACKGROUND: Recent randomized controlled trials (RCT) comparing different
      nonmechanical reperfusion strategies in patients with acute ST elevation
      myocardial infarction (AMI) (The GUSTO V, the ASSENT 3 and the HERO 2 trials)
      reported no differences in mortality, but lower nonfatal reinfarction rates in
      each best treatment arm during the hospital stay. METHODS: We analyzed the
      prospective observational Maximal Individual The rapy in Acute Myocardial
      Infarction (MITRA) data base selecting AMI patients similar to the RCT patients,
      to determine whether the observed differences in reinfarction rates will have an
      influence on longterm mortality. RESULTS: Out of 6737 patients included in MITRA
      between 1994 and 2000, 2109 (31%) fulfilled the selection criteria simulating the
      RCTs and were followed up for a median of 18 (quartiles: 16/22) months. Mortality
      at 1-year after discharge was 6.8% (95%CI: 2.3-11.3%) in patients with versus
      4.4% (95%CI: 3.5-5.3%) in patients without a non-fatal reinfarction (absolute
      difference 2.4%, p = 0.04 by log rank test). Transferred to the results of the
      RCTs, this difference would require more than 1 million patients in each
      treatment arm of the RCTs to show significant differences in long-term mortality.
      CONCLUSION: Non-fatal in-hospital reinfarctions were associated with a higher
      mortality during the 18 month follow-up in MITRA. However, because the observed
      differences in the rates of non-fatal in hospital reinfarctions between the
      treatment arms in the GUSTO V, the ASSENT 3 and the HERO 2 trials were very
      small, our data make it very improbable that they will result in lower 1-year
      mortality rates.

PMID- 14579050
TI  - Two year follow-up in 643 patients with non-invasively unexplained syncope and
      therapy guided by electrophysiologic study.
AB  - AIM: Although it has become standard practice to perform electrophysiologic
      studies in patients with unexplained syncope, limited information exists on
      prognosis after therapy guided by electrophysiologic studies. METHODS AND
      RESULTS: Electrophysiologic studies were performed in 643 patients with
      unexplained syncope. Electrophysiologic studies revealed conduction abnormalities
      and tachyarrhythmias accounting for syncope in 35% of patients. An ejection
      fraction </= 40%, a PR-interval > 2 s and injury are helpful parameters in
      predicting a positive electrophysiologic study. There was no difference regarding
      cumulative 2-year survival rate after therapy guided by positive
      electrophysiologic study compared to patients with negative electrophysiologic
      study. The cumulative 2-year survival free-of-syncope rate was significantly
      higher after therapy guided by electrophysiologic study compared to patients with
      negative electrophysiologic findings-for patients with organic heart disease
      (71.3% vs 48.5%, p < 0.001) and patients without disease (91.3% vs. 65.2%, p <
      0.001). Using a logistic regression model, a positive electrophysiologic study
      was associated with a favorable outcome; multiple syncopal events or organic
      heart disease were associated with an unfavorable outcome. CONCLUSION: The
      cumulative overall 2-year surival free-of-syncope rate is significantly higher in
      patients after therapy guided by electrophysiologic study compared to patients
      with negative electrophysiologic findings.

PMID- 14579051
TI  - [Acute hemodynamic effects of biventricular and left ventricular pacing in
      chronic pacemaker-dependent patients with advanced heart failure].
AB  - The beneficial hemodynamic effects of cardiac resynchronization in patients with
      intraventricular conduction delay have been demonstrated. The potential
      hemodynamic effects of cardiac resynchronization to compensate the pacing-induced
      left ventricular conduction delay in chronically paced heart failure patients are
      not as well established. The aim of the study was to evaluate the acute
      hemodynamic effects of biventricular and left ventricular pacing in chronically
      paced patients with advanced heart failure. Fourteen consecutive pacemaker or
      defibrillator patients with permanent atrial fibrillation and AV block (11 male,
      3 woman, mean age: 68 +/- 7 years) were enrolled in this study. There were 5
      ischemic (36%) and 9 nonischemic (64%) patients (mean left ventricular ejection
      fraction: 19 +/- 5%; mean end-diastolic left ventricular diameter: 71 +/- 11 mm).
      In all patients a right ventricular and left ventricular (via coronary sinus)
      pacing lead was placed. The aortic and left ventricular hemodynamic measurements
      were performed using a two-channel micro-tip catheter. The measurements of the
      aortic pulse pressure (APP) and (dP/ dtmax) were performed during right
      ventricular apical pacing (RVP), left ventricular (LVP), and biventricular pacing
      (BVP) (70 bpm). Compared to RVP, LVP and BVP increased APP and dP/dtmax (35.8 +/-
      4.2 vs 43.3 +/- 4.5 and 41.2 +/- 4 mmHg; p < 0.001) and (758 +/- 56 vs 967 +/- 60
      and 961 +/- 62 mmHg/s; p < 0.001). LVP and BVP showed a comparable hemodynamic
      response. The hemodynamic effects were not related to the width of the paced QRS
      complex. Every patient showed improved hemodynamics during LVP and BVP unrelated
      to the underlying heart disease and to the baseline level of left ventricular
      dysfunction. BVP and LVP pacing acutely improve contractile left ventricular
      function in chronically paced patients with advanced heart failure.

PMID- 14579052
TI  - Cardiac rehabilitation in patients with implantable defibrillators. Feasibility
      and complications.
AB  - OBJECTIVE: We examined patients with implantable cardioverter defibrillators
      (ICD) in order to demonstrate their safe participation in a standard
      rehabilitation program. DESIGN: Prospective cohort study of a consecutive series
      of patients after ICD implantation. Setting Inpatient rehabilitation center.
      PATIENTS AND METHODS: A total of 118 patients (73.7% male, mean age 60+/-11
      years) took part for 23 +/- 4 days in a standard inpatient rehabilitation program
      including physical activity, psychological care, heart function seminars, and
      resuscitation exercises with family members. The following noninvasive tests were
      performed: symptomlimited exercise testing, two-dimensional echocardiography,
      Holter monitoring, telemetric ICD interrogation, optional fluoroscopy or X-ray
      examination of the thorax, and (in some patients) defibrillation threshold
      testing. RESULTS: Out of 118 patients 101 patients (85.6%) participated in
      regular ergometer training during which the initial workload of 23 +/- 11 Watts
      could be increased to 45 +/- 18 Watts. An individual conditioning program was
      assigned to 15% (n = 17) patients, thereby enabling the inclusion of all patients
      in the rehabilitation process. Under these conditions 12 patients (10%)
      experienced ICD malfunctions requiring therapy. As a consequence of all cardiac
      function tests, ICD reprogramming was necessary in 26 patients (22.1%).
      CONCLUSION: Following ICD implantation, patients may participate in a standard
      rehabilitation program without serious complications and with a significant
      increase in physical capacity. However, ICD malfunction occurs in approximately
      10% of patients. Additional tests performed by skilled medical staff and
      appropriate technical equipment allows the ICD program to be optimized.

PMID- 14579054
TI  - [Catheter-based rescue of a split pacemaker lead in the pulmonary artery].
AB  - This case report describes a successful catheter-based rescue of a split
      pacemaker lead in the pulmonary artery-as an unusual reason for pleural effusion.
      Hemorrhagic pleural effusion was diagnosed 7 months after pacemaker exchange due
      to battery depletion and lead replacement due to an increase of the stimulation
      threshold. The reason for the pleural effusion was a splitting of the inactive
      electrode lead into shaft and inner fragment which was dislocated into the
      pulmonary artery and micro-perforated. The dislocated lead was retrieved using
      biopsy forceps and a gooseneck snare. Finally it was capped and fixed. Even in an
      anatomically difficult position, catheter-based rescue is feasible. Not in all
      pacemaker lead types is cutting the adapter of the inactive pacemaker leads
      recommendable.

PMID- 14579053
TI  - Myocardial contrast echocardiography for assessment of myocardial perfusion at
      rest in a patient with left main coronary artery stenosis.
AB  - The present case will focus on the potential of hypoperfusion detection with
      myocardial contrast echocardiography (MCE) using power Doppler harmonic imaging
      (PDHI). PDHI is normally performed in a triggered mode. Microbubbles were
      destroyed by the ultrasound energy in the myocardium, and myocardium has to be
      refilled with microbubbles within the time interval between the ultrasound pulses
      to obtain repetitive information about perfusion. Using the contrast agent
      Levovist, however, real-time PDHI also results in myocardial opacification
      presumably due to perfusion signals of the arteriolar microbubble passage. A 45
      year-old woman with typical stress-induced angina was admitted to our department
      for cardiac catheterization. Prior to the angiography a conventional
      echocardiogram showed normal left ventricular function. Tissue Doppler, however,
      demonstrated postsystolic longitudinal shortening of the septal, anterior, and
      lateral wall regions. Myocardial contrast echocardiography with triggered PDHI
      showed complete opacification of the myocardium at rest. Using real-time PDHI
      with Levovist, the septum could not be opacified. The consecutive angiography
      documented a severe unprotected main coronary artery stenosis. After angioplasty
      and stent implantation, MCE measurements were repeated. Repetitive intravenous
      bolus injections of Optison during triggered PDHI showed no differences to the
      investigation prior to the angioplasty. Using real-time PDHI with Levovist,
      however, there was a marked difference in comparison to the pre-interventional
      analysis. A complete opacification of the apical septum was observed. The present
      case suggests that different MCE techniques can analyze different compartments of
      the myocardial vasculature in clinical practice. This methodological comparison
      between triggered and real-time PDHI shows obviously differences in the DI signal
      detection due to the different microbubble behavior. Clinicians should be aware
      of the potentials of MCE to improve noninvasive diagnostic procedures in patients
      with ischemic heart disease.

PMID- 14579055
TI  - Amiodarone-associated "torsade de pointes". Relevance of concomitant
      cardiovascular medication in a patient with atrial fibrillation and structural
      heart disease.
AB  - A 69 year old female with history of coronary heart disease, myocardial
      infarction and paroxysmal atrial fibrillation suffered from occipital apoplexy.
      Under treatment with amiodarone 600 mg daily and concomitant medication with beta
      acetyldigoxine (0.1 mg daily) and bisoprolole (1.25 mg daily), significant QT
      prolongation (max. 700 ms; QTc: 614 ms) could be documented. Out of normofrequent
      sinus rhythm but as well out of bradycardia, the patient developed repetitive
      short-lasting "torsade de pointes" tachycardias (320 bpm) which terminated
      spontaneously. Serum electrolytes, plasma levels of digoxine (1.76 ng/ml) and
      amiodarone (1.9 mcg/ml) were within therapeutic range. This case report is the
      first to describe induction of amiodarone-associated "torsade de pointes"
      tachycardia during concomitant beta-blocker and digitalis medication in a patient
      with atrial fibrillation and structural heart disease. This points towards an
      elevated risk for proarrhythmia under this triple therapy.

PMID- 14579058
TI  - [Death with dignity].

PMID- 14579059
TI  - [Quality of life at the end of live: experiences, models and perspectives].
AB  - The present paper gives an overview of theoretical concepts and empirical
      research on the issue of quality of life at the end of life with a focus on
      psychological concepts of lifelong development. Faced with severe illness, it
      seems that in old age the quality of life strongly depends on the individuals'
      potentials for developmental change. In addition, particular qualities of the
      spatial, social, and care context, taking the psychosocial, spiritual and
      practical competences and needs of the patients and their relatives into account,
      seem to lead to a higher degree of self determination and well-being. Empirical
      findings on the predictors of quality of life and of a "good death" are reported.
      Implications for an adequate care context at the end of life and research needs
      are discussed.

PMID- 14579060
TI  - Technology and "natural death": a study of older people.
AB  - This paper reports a qualitative study in which the aim was to examine older
      peoples' beliefs and risk perceptions regarding the use of innovative health
      technologies in end-of-life care and to relate these beliefs to their ideas about
      'natural death'. Pictures, story boards and media extracts were used during
      interviews and focus groups, and the research team was assisted by an advisory
      group which included participants. Seventy-seven older people from three age
      cohorts (65-74; 75-84; 85 years and over) and from three contrasting areas of
      Sheffield, UK took part. Key messages are for the need to ensure that 'life
      prolonging' and 'basic care' technologies are provided in ways that respect a
      variety of understandings about love, comfort, obligation and burden during
      dying. The study highlights: the role that older people have in caring for the
      dying and their needs for support and training; information needs about issues of
      ethics, clinical practice and advance care planning; and the willingness of older
      research participants to discuss these matters and to enjoy the process of so
      doing. Developing a programme of public education and information was identified
      as an issue which should be addressed urgently if older people and their family
      carers are to be better equipped to make informed choices about these aspects of
      care. The study draws together issues previously considered under the largely
      separate remits of palliative care and gerontology. It is being used to provide
      advice on palliative and end-of-life care, especially to nursing and medical
      practitioners and to voluntary sector organisations as they begin to assess the
      need for action in this field.

PMID- 14579061
TI  - [Dying with dignity-between autonomy and care. A contribution to the current
      legal discussion in Germany].
AB  - The juridical discussion about "dying with dignity" in Germany is concentrated on
      the aspect of autonomy of the patients and the juridical instruments of "power of
      attorney". The aspects of care for dying patients and a multidimensional concept
      of dignity are in danger of being neglected. In the context of the discussion of
      rationing in the health sector the accentuation of the aspect of autonomy could
      support the development of new acceptance of euthanasia and the stoping of
      treatment. In this essay the current discussion in Germany will be shown with
      consideration of current legal decisions.

PMID- 14579062
TI  - [Palliative care for patients with advanced dementia: Evidence-based practice
      replaced by values-based practice].
AB  - For the treatment of patients with advanced dementia, we could not find any
      evidence based guidelines to help in decision making. Individual values and
      expected quality of life must be the leading goals of any intervention. Symptom
      control and relieving suffering are core values of palliative care, but the
      recognition of discomfort needs qualified assessment skills. Pain assessment with
      common tools like the VAS fails in patients with cognitive impairment and
      inability to communicate; instruments like Doloplus and ECPA can be helpful to
      assess behavioral changes as expression of pain. The treatment of acute and
      chronic pain in advanced dementia is still not sufficient and needs improvement.
      Oral feeding in advanced dementia becomes more and more difficult. No randomized
      controlled study has found evidence that tube feeding will reduce the risk of
      aspiration or prolong life expectancy. Eating may be the only meaningful activity
      that remains for the patient; artificial feeding cannot serve the same function.
      All final complications, like pneumonia, call for a decision making process.
      Those who care for and care about these patients must make decisions. The
      feelings of the family have to be considered, but the probable will of the
      patient, his dignity and quality of life must not be overridden.

PMID- 14579063
TI  - [Palliative culture in the stationary care for the elderly].
AB  - Nursing homes are challenged by a significant change in the patient-structure. To
      care for dying elderly people means to enable them to live in dignity till the
      end. Helpful therefore is to implement Palliative Care into existing structures.
      This requires personal and organizational learning and development. The first
      step is to make central differences and contradictions visible und communicable.
      We describe three organizational types which leads into different core-processes.
      Organizational measures supporting the development of a palliative culture and
      indicators of successful implementation are presented.

PMID- 14579064
TI  - [Geriatrics-quo vadis? The system of geriatric care].
AB  - The authors describe the current and perspective structure of geriatric care in
      hospital and rehabilitation units. First the specific needs of elderly patients
      with various medical problems (multiple morbidity) are described. Furthermore the
      article analyses optimised structures of geriatric care. These visions are not
      limited to care in hospital and rehabilitation units but include prevention and
      long term care for elderly people as well.

PMID- 14579065
TI  - [Preventative home visits by a specially trained nurse for 60-year olds and
      elderly in Hamburg].
AB  - There is increasing interest in home visits by phycisians, nurses or occupational
      therapists which offer health promotion or preventive care to older people.
      However, the practical performance of home visits, the targeting, and the
      effectiveness are ambigious. The collaboration in the EU-study 'disability
      prevention' gave the opportunity to recruit non-selected people 60 years and
      older from 14 general practitioners' patient lists in Hamburg. The study
      participants were offered different programs of health promotion, i. e., group
      sessions at the geriatric center and preventive home visits. The home visits were
      made by a nurse who received special training, and a curriculum was established.
      Seventy-seven elderly persons were visited because they were not able to attend
      the group sessions at the geriatric center due to self-reported problems in
      mobility. The investigations revealed combined risks for development of
      functional decline and dependency in the majority of these community dwelling
      elderly persons. These findings were unknown to the general practitioners. For
      example, the risk of falling as recorded by assessment was elevated in more than
      half of the persons visited. Screening and assessment are useful for planing
      measures of health promotion and prevention. There are still questions open to
      discussion. The targeting, practicability, and prerequisites in structure of
      service provision are considered with regard to the present study's results and
      an upto date literature review.

PMID- 14579066
TI  - [Desire for death-results of a pilot study with acute geriatric patients].
AB  - Desire for death when expressed by patients is extremely demanding to the
      geriatric team. In an acute geriatric setting with its high proportion of multi
      morbid patients, decisions about diagnostic and therapeutic measures as well as
      decisions about restrictions of therapy have vital consequences. In this context,
      what is the significance of expressions of desire for death? A growing amount of
      literature has reported about studies on such questions with terminally ill
      patients. Studies in the field of acute geriatrics are still missing. In the
      present explorative pilot study, data of ten patients in an acute geriatric
      setting were collected within a two-month period. Data comprise various
      dimensions of the expressions of desire for death, and variables of their medical
      psychiatric, psychological, and psycho-social context. The dimensions of
      duration, intensity, and concreteness could be differentiated within the
      expressions of desire for death. In addition, they were each correlated to
      different context variables. Intensity was associated with experiences of pain.
      Subjective well-being and social support were relevant to concreteness. Duration
      was correlated with depression, hopelessness, experienced stress, and functional
      health. Physical health did not play a significant role. This means that
      expressions of desire for death do not only occur in the context of extreme
      health problems. The study has identified differentiated starting points for
      better understanding the expressions of desire for death and for better
      intervention. Further study is necessary to confirm these findings within a
      longitudinal design.

PMID- 14579070
TI  - Omental infarction: an unusual cause of acute abdomen in children.
AB  - Acute abdomen is caused by a wide variety of etiologies, many of which require
      surgical intervention. Two boys were hospitalized for acute abdominal pain and
      low-grade fever. Physical examination revealed epigastric and right upper
      abdominal fullness, and laboratory studies showed elevated erythrocyte
      sedimentation rates, with normal leukocyte counts and coagulation profiles.
      Abdominal ultrasound and computerized tomography revealed pseudotumor in both
      cases. Symptomatic treatment and cefazolin were administered, and pain and fever
      subsided after 6 to 10 days. Pseudotumor due to omental infarction can present as
      acute abdomen in children. A high index of suspicion and the use of both
      ultrasonography and computerized tomography will help avoid unnecessary surgical
      intervention in such cases.

PMID- 14579071
TI  - Successful excision of a congenital, prenatally diagnosed fibrosarcoma involving
      the entire right ovary.
AB  - This report describes a congenital fibrosarcoma (CFS) of the ovary presenting as
      an abdominal mass on prenatal ultrasonography. Few cases of intrauterine CFS have
      been reported to date. When CFS develops prenatally, it usually grows rapidly,
      and resection is difficult at birth. We successfully resected a tumor after
      birth, and there has been no recurrence after 2 years. This patient is the first
      known survivor of CFS diagnosed prenatally.

PMID- 14579072
TI  - Operating and anaesthetic time required for inguinal hernia repair in the
      neonate.
AB  - Inguinal hernia repair in neonates can be a challenging operation and
      anaesthetic. However, there is no information on how much anaesthetic and
      operating time is required for such surgery. Planning operating time and
      resources requires this knowledge. This study looked at 94 neonatal hernia
      repairs and compared anaesthetic and operating times for these patients with 297
      day-case hernia repairs. The median anaesthetic and operating times for neonates
      with unilateral repair were 20 and 45 min compared with 13 and 30 min for day
      cases. However, the ranges for anaesthetic time (10-185 min) and operating time
      (20-170 min) were considerably in excess of those for day-cases (0-54 and 15-80
      min) respectively. Neonatal hernia operations accounted for a total of one
      theatre list per month in our centre.

PMID- 14579073
TI  - Nd-YAG laser core-through urethrotomy in obliterative posttraumatic urethral
      strictures in children.
AB  - This study analysed the feasibility and effectiveness of Nd-YAG laser core
      through urethrotomy in the management of obliterative posttraumatic urethral
      strictures in children. Between May 1997 and April 2000, 61 patients underwent
      core-through urethrotomy in posttraumatic urethral strictures, ten of whom were
      children (ages 5-15 years). Three patients had had previous railroading
      procedures, two attempted core-through urethrotomy, and two underwent end-to-end
      urethroplasties. Patients were on suprapubic cystostomy for a mean period of 12
      months with mean stricture length of 2 cm. Nd-YAG laser core-through urethrotomy
      was carried out using 600- micro m bare-contact fibre as a day care procedure.
      There were no intraoperative or postoperative complications. Micturating
      cystourethrography was performed 6 weeks following urethral catheter removal.
      Urethroscopy and uroflowmetry were carried out after 3 months. Mean follow-up was
      24 months.Nd-YAG laser core-through urethrotomy was seen to be successful in all
      patients without any complications. All patients are voiding without obstructive
      symptoms. Four required optical urethrotomy/endoscopic dilatation at least twice.
      Nd-YAG laser core-through urethrotomy is a safe and effective procedure for the
      management of obliterative posttraumatic urethral strictures in children

PMID- 14579074
TI  - A new oral testosterone undecanoate formulation.
AB  - Testosterone undecanoate has been available on the market for more than 20 years.
      This testosterone ester is used worldwide for oral treatment of male
      hypogonadism. So far, testosterone undecanoate has been dissolved in oleic acid,
      leading to inconvenient storage conditions. It will now be available in a new
      formulation with castor oil and propylene glycol laurate instead of oleic acid,
      thus improving storage conditions markedly (stable at room temperature for
      approximately 3 years). Pharmacokinetic and pharmacodynamic studies have
      demonstrated bioequivalence of the old and the new formulation of testosterone
      undecanoate. Therefore, the results of studies that were performed with the old
      formulation can be transferred to the clinical use of the new formulation.
      Controlled studies have shown its efficacy in the treatment of symptoms
      associated with reduced serum testosterone levels. In these cases testosterone
      undecanoate improves bone mineral density, quality of life, muscle mass, libido
      and mood. Further studies will help evaluate the efficacy and safety of the new
      formulation in the treatment of elderly men with late-onset hypogonadism.

PMID- 14579075
TI  - Cloning and expression of 1-aminocyclopropane-1-carboxylate synthase cDNA from
      rosa (Rosa x hybrida).
AB  - The role of 1-aminocyclopropane-1-carboxylate (ACC) synthase in rose flower petal
      senescence was investigated. A cDNA library from senescing petals of rose ( Rosa
      x hybrid cv. Kardinal) prepared in lambdacDNA ZAP Express Vector was probed with
      a rose-specific 400-bp probe, and seven putative positive ACC synthase clones
      were isolated. Except for differences in length, the sequences of these clones
      were identical. A full-length clone, RKacc7, 1,750 bp long, coded for an open
      reading frame of 480 amino acids that contained the 11 conserved amino acid
      residues, the substrate and pyridoxal 5'-phosphate binding sites, all of which
      are characteristic of all ACC synthases. The transcripts prepared in vitro from
      the full-length clone when translated in rabbit reticulocyte lysates exhibited a
      55-KDa polypeptide that comigrated with a polypeptide synthesized from a mRNA
      fraction isolated from senescing petals, and both were immunoselected by anti-ACC
      synthase antibodies. Reverse transcriptase-PCR-based studies showed that in
      planta RKacc7 is specifically expressed in rose petals, ovary and sepals. The
      expression of ACC synthase increased dramatically as the flower matured to
      senescence and also correlated positively with ethylene levels. The results of
      genomic Southern blots probed with RKacc7 are consistent with a pattern expected
      from a multigene family.

PMID- 14579077
TI  - Vascularized pedicled iliac crest graft for selected total hip acetabular
      reconstructions: a cadaver study.
AB  - Bone grafting is an essential part of most total hip acetabular reconstructions.
      There are a limited number of surgical options, each with inherent disadvantages
      for the management of structural acetabular defects. In this cadaver study, the
      authors aimed to evaluate the availability of vascularized pedicled iliac crest
      graft for the purpose of acetabular reconstruction. The hip joints, ilia and deep
      circumflex iliac artery pedicles of six adult preserved cadavers were dissected
      bilaterally. A segment of the iliac crest was elevated on the vascular pedicle
      and its access to different parts of the acetabulum was evaluated. The average
      pedicle length was sufficient for coverage of the superior and anterior
      acetabular walls. The access to the posterior wall, however, required
      modification of the bone size. A vascularized pedicled iliac crest graft is
      suitable for the reconstruction of selected acetabular deficiencies.

PMID- 14579079
TI  - Topographic relationship between the cochlea and the middle fossa floor: the
      anatomical basis for an alternative approach to the cochlear turns.
AB  - The cochlea has attained extreme surgical interest since cochlear implantation
      has been recognized as an established method for the management of certain types
      of bilateral profound hearing loss. Traditionally access to the cochlear turns is
      achieved through the middle ear. Extremely limited references exist in the
      literature regarding alternative surgical approaches to the cochlea. In the
      present study we tried to highlight the anatomic relationships of the superior
      aspect of the bony cochlea to the adjacent superficial structures of the petrous
      bone, as there have been suggestions that the cochlea is surgically accessible
      through the floor of the middle cranial fossa (MCF). A total of 58 dry human
      adult skulls (116 temporal bones) were studied. The groove for the greater
      superficial petrosal nerve (GGSPN) and the facial hiatus were used as landmarks
      in order to expose the superior aspect of the cochlea. Measurements were made of
      the following distances: a) between the MCF floor and the superficial part of the
      basal turn (SPBT), b) between the MCF floor and the apex of the cochlea, c)
      between the SPBT and the GGSPN and d) between the SPBT medially and the first
      genu of the facial canal laterally. Our results indicate that adequate and
      reliable surgical access to the bony cochlea could be achieved through the MCF
      floor.

PMID- 14579081
TI  - Cost-effectiveness of FDG-PET in staging non-small cell lung cancer: the PLUS
      study.
AB  - Currently, up to 50% of the operations in early-stage non-small cell lung cancer
      (NSCLC) are futile owing to the presence of locally advanced tumour or distant
      metastases. More accurate pre-operative staging is required in order to reduce
      the number of futile operations. The cost-effectiveness of fluorine-18
      fluorodeoxyglucose positron emission tomography ((18)FDG-PET) added to the
      conventional diagnostic work-up was studied in the PLUS study. Prior to invasive
      staging and/or thoracotomy, 188 patients with (suspected) NSCLC were randomly
      assigned to conventional work-up (CWU) and whole-body PET or to CWU alone. CWU
      was based on prevailing guidelines. Pre-operative staging was followed by 1 year
      of follow-up. Outcomes are expressed in the percentage of correctly staged
      patients and the associated costs. The cost price of PET varied between <euro>736
      and <euro>1,588 depending on the (hospital) setting and the procurement of
      (18)FDG commercially or from on-site production. In the CWU group, 41% of the
      patients underwent a futile thoracotomy, whereas in the PET group 21% of the
      thoracotomies were considered futile ( P=0.003). The average costs per patient in
      the CWU group were <euro>9,573 and in the PET group, <euro>8,284. The major cost
      driver was the number of hospital days related to recovery from surgery.
      Sensitivity analysis on the cost and accuracy of PET showed that the results were
      robust, i.e. in favour of the PET group. The addition of PET to CWU prevented
      futile surgery in one out of five patients with suspected NSCLC. Despite the
      additional PET costs, the total costs were lower in the PET group, mainly due to
      a reduction in the number of futile operations. The additional use of PET in the
      staging of patients with NSCLC is feasible, safe and cost saving from a clinical
      and from an economic perspective.

PMID- 14579082
TI  - A diagnostic strategy for pulmonary embolism based on standardised pretest
      probability and perfusion lung scanning: a management study.
AB  - Pulmonary embolism remains a challenging diagnostic problem. We developed a
      simple diagnostic strategy based on combination of assessment of the pretest
      probability with perfusion lung scan results to reduce the need for pulmonary
      angiography. We studied 390 consecutive patients (78% in-patients) with suspected
      pulmonary embolism. The pretest probability was rated low (<10%), intermediate
      (>10%, < or =50%), moderately high (>50%, < or =90%) or high (>90%) according to
      a structured clinical model. Perfusion lung scans were independently assigned to
      one of four categories: normal; near-normal; abnormal, suggestive of pulmonary
      embolism (wedge-shaped perfusion defects); abnormal, not suggestive of pulmonary
      embolism (perfusion defects other than wedge shaped). Pulmonary embolism was
      diagnosed in patients with abnormal scans suggestive of pulmonary embolism and
      moderately high or high pretest probability. Patients with normal or near-normal
      scans and those with abnormal scans not suggestive of pulmonary embolism and low
      pretest probability were deemed not to have pulmonary embolism. All other
      patients were allocated to pulmonary angiography. Patients in whom pulmonary
      embolism was excluded were left untreated. All patients were followed up for 1
      year. Pulmonary embolism was diagnosed non-invasively in 132 patients (34%), and
      excluded in 191 (49%). Pulmonary angiography was required in 67 patients (17%).
      The prevalence of pulmonary embolism was 41% ( n=160). Patients in whom pulmonary
      embolism was excluded had a thrombo-embolic risk of 0.4% (95% confidence
      interval: 0.0%-2.8%). Our strategy permitted a non-invasive diagnosis or
      exclusion of pulmonary embolism in 83% of the cases (95% confidence interval: 79%
      86%), and appeared to be safe.

PMID- 14579083
TI  - A new, practical, low-dose 14C-urea breath test for the diagnosis of Helicobacter
      pylori infection: clinical validation and comparison with the standard method.
AB  - The carbon-14 urea breath test (UBT) is a reliable and non-invasive technique for
      the diagnosis of Helicobacter pylori (HP) infection. In this study we evaluated
      the diagnostic performance of a new, practical and low-dose (14)C-UBT system for
      the diagnosis of HP and compared the results with those obtained using the
      standard method. Seventy-five patients (56 female, 19 male) with dyspepsia
      underwent (14)C-UBT and endoscopy with antral biopsies for histological analysis.
      The rapid urease test (CLO test) was applied to 50 of these patients. After a 6-h
      fasting period, a 37-kBq (14)C-urea capsule was swallowed for UBT. Breath samples
      were collected and counted using two different methods, the Heliprobe method and
      the standard method. In the Heliprobe method, patients exhaled into a special dry
      cartridge system (Heliprobe BreathCard) at 10 min. The activities of the
      cartridges were counted using a designated small GM counter system (Heliprobe
      analyser). Results were expressed both as counts per minute (HCPM) and as grade
      (0, not infected; 1, equivocal; 2, infected) according to the counts. In the
      standard method, breath samples were collected by trapping in a liquid CO(2)
      absorber. Radioactivity was counted as disintegrations per minute (SDPM) using a
      liquid scintillation counter after addition of a liquid scintillation cocktail.
      Histological examination was used as a gold standard. Two patients were excluded
      from the study because of inadequate biopsy sampling. Forty-eight patients (65%)
      were found to be HP positive on histology. The Heliprobe method correctly
      classified 48 of 48 HP-positive patients and 19 of 25 HP-negative patients
      (sensitivity 100%, specificity 76%, PPV 88%, NPV 100%, accuracy 91%). The
      standard method correctly classified 48 of 48 HP-positive patients and 20 of 25
      HP-negative patients (sensitivity 100%, specificity 80%, PPV 90%, NPV 100%,
      accuracy 93%). On the other hand, the CLO test identified 26 of 32 HP-positive
      and 12 of 16 HP-negative patients (sensitivity 81%, specificity 75%, PPV 86%, NPV
      66%, accuracy 79%). With the Heliprobe method, all of the positive results were
      grade 2, and all of the negative results were grade 0. No patients were defined
      as having grade 1 results. Counts allowed clear discrimination of HP-positive and
      -negative patients with both methods, the difference being statistically
      significant in each case ( P<0.001). A significant correlation was found between
      HCPM and SDPM ( r 0.863, P<0.001). According to the ROC analysis, the area under
      the curve was nearly the same with HCPM (AUC, 0.888; 95% CI, 0.785-0.992) and
      SDPM (AUC, 0.898; 95% CI, 0.802-0.994). In conclusion, the new (14)C-UBT system
      is a highly accurate method for the diagnosis of HP infection. It is rapid and
      practical, and therefore suitable for clinical and office practice.

PMID- 14579084
TI  - Immunoscintigraphy of septic loosening of knee endoprosthesis: a retrospective
      evaluation of the antigranulocyte antibody BW 250/183.
AB  - Immunoscintigraphy with the use of the antigranulocyte antibody BW 250/183 is a
      reliable method for detecting infection, especially in septic loosening of hip
      prostheses, for which purpose quantitative interpretation of the time-activity
      course is employed. Therefore, we retrospectively studied whether similar results
      could be achieved in knee prostheses. We verified 28 scintigraphic examinations
      in 26 patients by histology. Scintigraphy was performed during an early (4-6 h
      post injection) and a late phase (23-25 h post injection). Infection was
      diagnosed when activity around the knee prosthesis increased by more than 10%
      compared with bone marrow. We found a sensitivity and a negative predictive value
      of 100%, a specificity of 80%, a positive predictive value of 81% and an accuracy
      of 89%. Specificity and accuracy are lower than in the evaluation of hip
      prostheses; however, in comparison to other scintigraphic modalities,
      scintigraphy with the antigranulocyte antibody BW 250/183 is superior in
      excluding infection and has better specificity and accuracy. Therefore, as in the
      case of hip prostheses, the described methodology appears to be the scintigraphic
      modality of choice for knee prostheses.

PMID- 14579085
TI  - Usefulness of 18F-FDG PET in intrahepatic cholangiocarcinoma.
AB  - Surgical resection is the only curative treatment strategy for intrahepatic
      cholangiocarcinoma (CC). Therefore, accurate staging is essential for appropriate
      management of patients with CC. We assessed the usefulness of 2-[(18)F]fluoro-2
      deoxy- d-glucose (FDG) positron emission tomography (PET) in the staging of CC.
      We undertook a retrospective review of FDG PET images in 21 patients (10 female,
      11 male; mean age 57 years) diagnosed with CC. Ten patients had hilar CC and 11,
      peripheral CC. Patients underwent abdominal magnetic resonance imaging (MRI) (
      n=20) and computed tomography (CT) ( n=12) for the evaluation of primary tumours,
      and chest radiography and whole-body bone scintigraphy for work-up of distant
      metastases. For semi-quantitative analysis, the maximum voxel standardised uptake
      value (SUV(max)) was obtained from the primary tumour. All peripheral CCs showed
      intensely increased FDG uptake, and some demonstrated ring-shaped uptake
      corresponding to peripheral rim enhancement on CT and/or MRI. In nine of the ten
      patients, hilar CCs demonstrated increased FDG uptake of a focal nodular or
      linear branching appearance. The remaining case was false negative on FDG PET.
      One patient with a false negative result on MRI demonstrated increased uptake on
      FDG PET. Among the ten hilar CCs, FDG uptake was intense in only two patients and
      was slightly higher than that of the hepatic parenchyma in the remaining
      patients. For the detection of lymph node metastasis, FDG PET and CT/MRI were
      concordant in 16 patients, and discordant in five (FDG PET was positive in three,
      and CT and MRI in two). FDG PET identified unsuspected distant metastases in four
      of the 21 patients; all of these patients had peripheral CC. FDG PET is useful in
      detecting the primary lesion in both hilar and peripheral CC and is of value in
      discovering unsuspected distant metastases in patients with peripheral CC. FDG
      PET could be useful in cases of suspected hilar CC with non-confirmatory biopsy
      and radiological findings.

PMID- 14579086
TI  - Regional cerebral blood flow assessed with 99mTc-ECD SPET as a marker of
      progression of mild cognitive impairment to Alzheimer's disease.
AB  - Patients diagnosed with mild cognitive impairment (MCI) have a higher risk of
      developing Alzheimer's disease (AD). However, not all such patients develop this
      kind of dementia. The purpose of this prospective study was to assess whether
      regional cerebral blood flow (rCBF) patterns measured with technetium-99m ethyl
      cysteinate dimer single-photon emission tomography ((99m)Tc-ECD SPET) in patients
      suffering from MCI are useful in predicting progression to AD. The study group
      comprised 42 patients who fulfilled MCI criteria according to the International
      Psychogeriatric Association and the Alzheimer's Disease Cooperative Study. rCBF
      was calculated in 16 regions of interest (ROIs). All patients were clinically
      assessed for 1-3 years. Twenty-one developed AD (group I) while the initial
      diagnosis of MCI was retained in the other 21 (group II). ROC curves were
      designed, and sensitivity, specificity, positive and negative predictive values,
      and positive and negative likelihood ratios were determined for each ROI.
      Compared with group II (MCI), group I (AD) showed a significant reduction of
      relative blood flow (RBF), ranging from 7% to 10%, in the following areas: right
      and left prefrontal, right and left frontal, right and left parietal, right and
      left temporal, right and left frontoparietotemporal and left posterior lateral
      temporal. Left prefrontal, left frontal and left parietal areas showed
      sensitivities and specificities higher than 75% and areas below the ROC curve
      close to 80%. This study shows that RBF patterns in the right and left
      prefrontal, right and left frontal and left parietal areas are sensitive early
      markers of progression towards AD. Reduction of rCBF in the medial temporal and
      anterior lateral temporal cortex has no value as a predictor since it also occurs
      in patients with MCI who remain stable.

PMID- 14579087
TI  - A new approach for improving diagnostic accuracy in Alzheimer's disease and
      frontal lobe dementia utilising the intrinsic properties of the SPET dataset.
AB  - Alzheimer's disease (AD) and frontal lobe dementia (FLD) show characteristic
      patterns of regional cerebral blood flow (rCBF). However, these patterns may
      overlap with those observed in the aging brain in elderly normal individuals. The
      aim of this study was to develop a new method for better classification and
      recognition of AD and FLD cases as compared with normal controls. Forty-six
      patients with AD, 7 patients with FLD and 34 normal controls (CTR) were included
      in the study. rCBF was assessed by technetium-99m hexamethylpropylene amine oxime
      and a three-headed single-photon emission tomography (SPET) camera. A brain atlas
      was used to define volumes of interest (VOIs) corresponding to the brain lobes.
      In addition to conventional image processing methods, based on count
      density/voxel, the new approach also analysed other intrinsic properties of the
      data by means of gradient computation steps. Hereby, five factors were assessed
      and tested separately: the mean count density/voxel and its histogram, the mean
      gradient and its histogram, and the gradient angle co-occurrence matrix. A
      feature vector concatenating single features was also created and tested.
      Preliminary feature discrimination was performed using a two-sided t-test and a K
      means clustering was then used to classify the image sets into categories.
      Finally, five-dimensional co-occurrence matrices combining the different
      intrinsic properties were computed for each VOI, and their ability to recognise
      the group to which each individual scan belonged was investigated. For correct
      classification of the AD-CTR groups, the gradient histogram in the parieto
      temporal lobes was the most useful single feature (accuracy 91%). FLD and CTR
      were better classified by the count density/voxel histogram (frontal and
      occipital lobes) and by the mean gradient (frontal, temporal and parietal lobes,
      accuracy 98%). For AD and FLD the count density/voxel histogram in the frontal,
      parietal and occipital lobes classified the groups with the highest accuracy
      (85%). The concatenated joint feature correctly classified 96% of the AD-CTR, 98%
      of the FLD-CTR and 94% of the AD-FLD cases. 5D co-occurrence matrices correctly
      recognised 98% of the AD-CTR cases, 100% of the FLD-CTR cases and 98% of the AD
      FLD cases. The proposed approach classified and diagnosed AD and FLD patients
      with higher accuracy than conventional analytical methods used for rCBF-SPET.
      This was achieved by extracting from the SPET data the intrinsic information
      content in each of the selected VOIs.

PMID- 14579088
TI  - Regional differences between 99mTc-ECD and 99mTc-HMPAO SPET in perfusion changes
      with age and gender in healthy adults.
AB  - A number of studies using single-photon emission tomography (SPET) have shown
      perfusion changes with age in several cortical and subcortical areas, which might
      distort the results of perfusion imaging studies of neuropsychiatric disorders.
      Technetium-99m labelled ethyl cysteinate dimer (ECD) and hexamethylpropylene
      amine oxime (HMPAO) are both used as markers of cerebral perfusion, but have
      different pharmacokinetics and retention patterns. The aim of this study was to
      determine whether age and gender effects on perfusion SPET differ depending on
      whether (99m)Tc-HMPAO or (99m)Tc-ECD is used. Forty-five subjects (20 male and 25
      female, mean age 52.8+/-6.6 years) were assigned to (99m)Tc-HMPAO SPET (HMPAO
      group), and 39 subjects (24 male and 15 female, mean age 52.6+/-6.7 years) to
      (99m)Tc-ECD SPET (ECD group). SPET images were obtained about 10 min after
      intravenous injection of approximately 800 MBq (99m)Tc-HMPAO or (99m)Tc-ECD using
      the same SPET scanner. Three-dimensional volumetric magnetic resonance imaging
      was performed to as7sess morphological changes in the grey matter. All image
      processing and statistical analyses were performed using SPM99 software. An area
      in the right anterior frontal lobe showed an increase in perfusion with age only
      in the HMPAO group, whereas areas in the bilateral retrosplenial cortex showed
      decreases in perfusion with age only in the ECD group; neither group showed
      corresponding changes in the grey matter. The present study shows that different
      effects of age on perfusion are observed depending on whether (99m)Tc-HMPAO and
      (99m)Tc-ECD is used. This suggests that the results of perfusion SPET are
      differently confounded depending on the tracer used, and that perfusion SPET with
      these tracers has limitations when used in research on subtle perfusion changes.

PMID- 14579089
TI  - Comparison of 180 degrees and 360 degrees data acquisition for determination of
      left ventricular function from gated myocardial perfusion tomography and gated
      blood pool tomography.
AB  - The purpose of this study was to address the issue of 180 degrees versus 360
      degrees data collection for left ventricular ejection fraction (LVEF) and left
      ventricular volume measurements using gated myocardial perfusion tomography
      (gMPT) and gated blood pool tomography (gBPT). Thirty patients with known
      coronary artery disease were injected in a random sequence with 925 MBq of
      technetium-99m tetrofosmin and, within 2 days, with 740 MBq of (99m)Tc-labelled
      human serum albumin. gMPT and gBPT were acquired using 360 degrees data
      collection and reconstructed by filtered backprojection using all the acquired
      projection images and separately using only projection images acquired from 45
      degrees LPO to 45 degrees RAO. In order to have the same global count densities,
      the counts in the 360 degrees data set were redistributed using binomial deviates
      just before reconstruction. After reorientation along the left ventricular long
      axis, LVEF and left ventricular volumes were calculated using fully automatic
      algorithms. Twenty-eight patients also underwent planar radionuclide
      angiocardiography (PRNA) on the same day as the gBPT. For the gMPT studies, the
      correlation between 180 degrees data collection and 360 degrees data collection
      was excellent ( r>0.98). Bland-Altman analysis revealed small systematic and
      random differences (<6%) between 180 degrees and 360 degrees. For the gBPT
      studies, the correlation between 180 degrees data collection and 360 degrees data
      collection was very good ( r>0.93). However, Bland-Altman analysis revealed
      systematic differences of 26% and random differences of 17%. When PRNA was used
      as a reference, the best results were obtained with gMPT acquired using 180
      degrees data, while the worst results were obtained with gBPT acquired using 180
      degrees data. In conclusion, when evaluating LVEF and left ventricular volumes
      from gMPT, either 180 degrees or 360 degrees orbits can be used. However, 360
      degrees data acquisition is recommended when evaluating LVEF and left ventricular
      volumes from gBPT.

PMID- 14579090
TI  - Effect of attenuation correction on the interpretation of 99mTc-sestamibi
      myocardial perfusion scintigraphy: the impact of 1 year's experience.
AB  - The aim of this study was to determine the yield of attenuation correction in
      myocardial perfusion imaging (MPI), before and after a 1-year experience period.
      In 48 consecutive patients referred for MPI, both non-corrected (NC) and
      attenuation-corrected (AC) images were analysed by three independent readers
      shortly after implementation of attenuation correction. The same images were re
      analysed 1 year later, after having obtained experience in attenuation correction
      on a routine basis in >500 patients with clinical feedback. Results were compared
      with gold standards for ischaemia and infarction based on coronary angiography,
      follow-up, ultrasound and gated blood pool imaging. Sensitivity and specificity
      for the detection of coronary artery disease were 95% and 45% respectively for NC
      images and 77% and 70% respectively for AC images at first readings. After 1 year
      of AC experience, NC sensitivity/specificity was 100%/61%, and AC results were
      89%/92%. It is concluded that attenuation correction improves the performance of
      MPI interpretation. With attenuation correction, specificity is increased and
      sensitivity is similar as compared with NC images. However, attenuation
      correction requires experience and is associated with a learning curve.

PMID- 14579091
TI  - Optimisation of the OS-EM algorithm and comparison with FBP for image
      reconstruction on a dual-head camera: a phantom and a clinical 18F-FDG study.
AB  - Iterative reconstruction algorithms, such as the ordered subsets expectation
      maximisation (OS-EM), are a promising alternative to filtered backprojection
      (FBP). The aims of this study were first to optimise the OS-EM algorithm in terms
      of iteration number and to study the usefulness of post-filtering, and second to
      compare OS-EM and FBP for image reconstruction on a fluorine-18
      fluorodeoxyglucose ((18)F-FDG) dual-head camera (DHC). These two goals were
      addressed using phantom acquisitions. The performances of these algorithms were
      also studied in patient acquisitions performed on a DHC and a PET on the same
      day. Phantom experiments were performed on a DHC using a Jaszczak phantom
      containing six spheres filled with (18)F-FDG, two background levels (0.95, 6.80
      kBq/ml) and three object contrasts (5.9, 3.7, 2.7). The reconstruction algorithms
      were FBP with a Gaussian filter (FWHM 0.5-2 pixel width) and OS-EM using 8-128
      equivalent iterations (equivalent to the ML-EM algorithm) with and without
      Gaussian post-filtering [OS-EM (iterations, pixel width)]. Contrast recovery
      coefficient (CRC) and noise characteristics were assessed. Twenty-two patients
      (21 male, one female; age 55+/-15 years) with lung cancer underwent, on the same
      day, PET (1 h post injection of 37 MBq/kg (18)F-FDG) and DHC acquisitions (3 h
      post injection). DHC data were reconstructed using six methods: FBP (1), OS-EM
      (16), (40), (40,1), (64) and (64,1). These sets were evaluated by two observers
      and compared to PET reconstructed with OS-EM (16). The number of detected lesions
      and the visual quality were assessed. A marked improvement in CRC was observed
      with OS-EM as compared with FBP when more than 24 iterations were used. The CRC
      increased markedly from 8 to 40 iterations and then reached a plateau. The noise
      was stable until 40 iterations and then increased. The best compromise was
      obtained for OS-EM (32) and OS-EM (40,1). For the patient study, OS-EM provided
      images of better visual quality, but with no significant difference in detection
      sensitivity. OS-EM was superior to FBP in terms of contrast recovery and noise
      level. The optimal compromise between contrast recovery and noise was obtained
      for OS-EM (32) and (40,1) on the phantom study. The clinical study showed that OS
      EM yielded images of better visual quality but with no improvement in terms of
      detection of lung cancer.

PMID- 14579094
TI  - Assessment of left ventricular diastolic function by gated single-photon emission
      tomography: comparison with Doppler echocardiography.
AB  - Gated single-photon emission tomography (SPET) is not yet an established
      procedure for the evaluation of left ventricular (LV) diastolic function. This
      study examined diastolic function derived from gated SPET in comparison with an
      established diagnostic tool, Doppler echocardiography. We examined 37 consecutive
      patients with normal sinus rhythm who underwent gated technetium-99m tetrofosmin
      SPET. A gated SPET program was used with a temporal resolution of 32 frames per R
      R interval. We obtained the Doppler transmitral flow velocity waveform
      immediately before gated SPET image acquisition. Patients who showed a ratio of
      peak early transmitral flow velocity to atrial flow velocity (E/A) of >1 or whose
      R-R intervals differed by >5% between Doppler echocardiography and gated SPET
      were excluded from this investigation. We compared diastolic indices and presumed
      corresponding intervals in diastole using the two methods. The peak filling rate
      (PFR) derived from gated SPET correlated with the Doppler peak velocity of the
      early transmitral flow (E) wave ( r=0.65) and deceleration of the E wave (
      r=0.71). The time to PFR and percent atrial contribution to LV filling from gated
      SPET correlated excellently with the Doppler LV isovolumic relaxation time (
      r=0.93) and the E/A ratio ( r=-0.85), respectively. There was a significant
      linear correlation in all the intervals from the R wave to the presumed
      corresponding diastolic points. The point of PFR in gated SPET and the peak of
      the E wave in Doppler echocardiography generally coincided. The onset of filling
      in gated SPET tended to be closer to the second heart sound than the start of the
      E wave in Doppler echocardiography. We conclude that gated SPET permits the
      assessment of not only myocardial perfusion and LV systolic function but also
      diastolic function, although there may be some errors in detection of the precise
      beginning of LV filling.

PMID- 14579092
TI  - Radioiodinated SB 207710 as a radioligand in vivo: imaging of brain 5-HT4
      receptors with SPET.
AB  - Single-photon emission tomography (SPET) and positron emission tomography (PET),
      when coupled to suitable radioligands, are uniquely powerful for investigating
      the status of neurotransmitter receptors in vivo. The serotonin subtype-4 (5
      HT(4)) receptor has discrete and very similar distributions in rodent and primate
      brain. This receptor population may play a role in normal cognition and memory
      and is perhaps perturbed in some neuropsychiatric disorders. SB 207710 [(1-butyl
      4-piperidinylmethyl)-8-amino-7-iodo-1,4-benzodioxan-5-carboxylate] is a selective
      high-affinity antagonist at 5-HT(4) receptors. We explored radioiodinated SB
      207710 as a possible radioligand for imaging 5-HT(4) receptors in vivo. Rats were
      injected intravenously with iodine-125 labelled SB 207710, euthanised at known
      times and dissected to establish radioactivity content in brain tissues.
      Radioactivity entered brain but cleared rapidly and to a high extent from blood
      and plasma. Between 45 and 75 min after injection, the ratios of radioactivity
      concentration in each of 12 selected brain tissues to that in receptor-poor
      cerebellum correlated with previous measures of 5-HT(4) receptor density
      distribution in vitro. The highest ratio was about 3.4 in striatum. SB 207710 was
      labelled with iodine-123 by an iododestannylation procedure. A cynomolgus monkey
      was injected intravenously with [(123)I]SB 207710 and examined by SPET. Maximal
      whole brain uptake of radioactivity was 2.3% of the injected dose at 18 min after
      radioligand injection. Brain images acquired between 9 and 90 min showed high
      radioactivity uptake in 5-HT(4) receptor-rich regions, such as striatum, and low
      uptake in receptor-poor cerebellum. At 169 min the ratio of radioactivity
      concentration in striatum to that in cerebellum was 4.0. In a second SPET
      experiment, the cynomolgus monkey was pretreated with a selective 5-HT(4)
      receptor antagonist, SB 204070, at 20 min before [(123)I]SB 207710 injection.
      Radioactivity in all brain regions was reduced almost to the level in cerebellum
      by 176 min after radioligand injection. These findings show that [(123)I]SB
      207710 is an effective radioligand for imaging brain 5-HT(4) receptors in vivo.

PMID- 14579093
TI  - Reduction of 99mTc-sestamibi and 99mTc-tetrofosmin uptake in MRP-expressing
      breast cancer cells under hypoxic conditions is independent of MRP function.
AB  - Hypoxia reduces the uptake of technetium-99m sestamibi (MIBI) in human cancer
      cell lines. In the current investigation, we attempted to identify the
      relationship between hypoxia-induced alteration of (99m)Tc-MIBI accumulation and
      expression of multi-drug resistance-associated protein (MRP) in the MCF7/WT
      breast cancer cell line and its subclonal cell line, MCF7/VP, which expresses
      high levels of MRP1. A second cationic compound, (99m)Tc-tetrofosmin (TF), was
      also examined. Cellular uptake of (99m)Tc-MIBI and (99m)Tc-TF was significantly
      higher in parental MCF7/WT cells than in MCF7/VP cells. Hypoxic conditions
      generated with a mixture of 95% N(2) and 5% CO(2) reduced cellular uptake of the
      two tracers in both parental MCF7/WT cells and MRP1-expressing MCF7/VP cells.
      Cell binding assay with iodine-125-labelled anti-MRP1 antibody demonstrated its
      specific binding to MCF7/VP cells. Hypoxia did not affect the amount of antibody
      bound to MCF7/VP cells. These results indicate that hypoxia-induced reduction of
      tracer uptake in tumour cells is a phenomenon independent of MRP function.

PMID- 14579095
TI  - Estimates of regional cerebral blood flow and 5-HT2A receptor density in
      impulsive, aggressive dogs with 99mTc-ECD and 123I-5-I-R91150.
AB  - Impulsive aggression in dogs has an important impact on human public health.
      Better insight into the pathophysiology of this phenomenon could lead to more
      adequate diagnosis and treatment. Indirect in vivo research on peripheral body
      fluids and post-mortem studies in impulsive animals and humans indicate a
      deficient serotonergic system in general and disturbances in the serotonin-2A (5
      HT2A) receptor in particular. In this study, brain perfusion and the 5-HT2A
      receptors were examined in impulsive, aggressive dogs, in comparison with a group
      of normally behaving animals. In order to decide which dogs to include in this
      study, owners were asked to describe the general behaviour of the dogs, the
      circumstances in which aggression occurred and their conduct during aggressive
      acts. Finally, 19 dogs were retained for this study, showing, according to
      different behavioural specialists, disinhibited dominance aggression. Functional
      imaging studies were performed on all these dogs. Single-photon emission
      tomography (SPET) was used to measure regional brain perfusion using technetium
      99m labelled ethyl cysteinate dimer (ECD). The 5-HT2A receptor binding properties
      were investigated using the selective radioligand iodine-123 labelled 5-I-R91150.
      A significant increase in uptake of the 5-HT2A radioligand was noted in all
      cortical areas. No significant alterations were found in regional cortical
      perfusion, indicating that the increased binding index was not a consequence of
      increased tracer delivery. This study supports a role for the serotonergic system
      in canine impulsive aggression.

PMID- 14579096
TI  - Comparison of [18F]FHBG and [14C]FIAU for imaging of HSV1-tk reporter gene
      expression: adenoviral infection vs stable transfection.
AB  - Earlier studies involving comparison of different reporter probes have shown
      conflicting results between pyrimidine nucleosides [e.g., 2'-fluoro-2'-deoxy-1
      beta- d-arabinofuranosyl-5-iodouracil (FIAU)] and acycloguanosine derivatives
      [e.g., penciclovir (PCV), 9-(4-fluoro-3-hydroxymethylbutyl)guanine (FHBG)]. We
      hypothesized that this reported discrepancy may be related to how the reporter
      gene is delivered to the cells-stably transfected vs adenoviral infection. We
      directly compared the uptake characteristics of [(18)F]FHBG, [(3)H]PCV, and
      [(14)C]FIAU in cell culture and in vivo using an adenoviral mediated gene
      transfer model and stably transfected cells. We further compared the uptake of
      three reporter probes using both HSV1-tk and a mutant HSV1-sr39tk expressing
      cells to assess the optimal reporter probe/reporter gene combination. [(14)C]FIAU
      accumulation was greater than that of [(3)H]PCV and [(18)F]FHBG in control cells
      and in HSV1-tk stably transfected cells ( P<0.001). After infection of C6 cells
      with AdCMV- HSV1-tk (1.5x10(8) pfu), [(18)F]FHBG and [(3)H]PCV accumulation was
      significantly greater than that of [(14)C]FIAU ( P<0.01). [(18)F]FHBG and
      [(3)H]PCV accumulated to a significantly greater extent than [(14)C]FIAU in C6
      stb-sr39tk+ and AdCMV- HSV1-sr39tk infected C6 cells ( P<0.001). Results from the
      nude mice supported the results in cell culture. [(14)C]FIAU led to significantly
      higher %ID/g in C6-stb-tk+ xenografts than [(18)F]FHBG ( P<0.05); however,
      compared with [(14)C]FIAU, [(18)F]FHBG led to as high %ID/g in HSV1-tk expressing
      hepatocytes and to significantly greater %ID/g in C6-stb-sr39tk+ xenografts and
      HSV1-sr39tk expressing hepatocytes. Dynamic sequential images showed that
      [(18)F]FHBG was well retained in HSV1-sr39tk expressing cells (C6-stb-sr39tk+)
      for at least 4 h after injection, while it was rapidly cleared from HSV1-tk
      expressing cells (MH3924A-stb-tk+). [(14)C]FIAU accumulated in HSV1-tk stably
      expressing cells to a greater extent than either [(3)H]PCV or [(18)F]FHBG.
      However, the accumulation of [(3)H]PCV and [(18)F]FHBG in adenoviral infected C6
      cells or hepatocytes was equivalent to or greater than that of [(14)C]FIAU. These
      results may be due to intracellular biochemical changes (e.g., thymidine) when
      cells are infected with adenovirus. For adenoviral studies, the [(18)F]FHBG/ HSV1
      sr39tk combination was shown to be more sensitive than the [(14)C]FIAU/ HSV1-tk
      combination HSV1-tk.

PMID- 14579097
TI  - Brain tumour imaging with PET: a comparison between [18F]fluorodopa and
      [11C]methionine.
AB  - Imaging of amino acid transport in brain tumours is more sensitive than fluorine
      18 2-fluoro-deoxyglucose positron emission tomography (PET). The most frequently
      used tracer in this field is carbon-11 methionine (MET), which is unavailable for
      PET centres without a cyclotron because of its short half-life. The purpose of
      this study was to evaluate the performance of 3,4-dihydroxy-6-[(18)F]fluoro
      phenylalanine (FDOPA) in this setting, in comparison with MET. Twenty patients
      with known supratentorial brain lesions were referred for PET scans with FDOPA
      and MET. The diagnoses were 18 primary brain tumours, one metastasis and one non
      neoplastic cerebral lesion. All 20 patients underwent PET with FDOPA (100 MBq, 20
      min p.i.), and 19 of them also had PET scans with MET (800 MBq, 20 min p.i.). In
      all but one patient a histological diagnosis was available. In 15 subjects,
      histology was known from previous surgical interventions; in five of these
      patients, as well as in four previously untreated patients, histology was
      obtained after PET. In one untreated patient, confirmation of PET was possible
      solely by correlation with MRI; a histological diagnosis became available 10
      months later. MET and FDOPA images matched in all patients and showed all lesions
      as hot spots with higher uptake than in the contralateral brain. Standardised
      uptake value ratios, tumour/contralateral side (mean+/-SD), were 2.05+/-0.91 for
      MET and 2.04+/-0.53 for FDOPA (NS). The benign lesion, which biopsy revealed to
      be a focal demyelination, was false positive, showing increased uptake of MET and
      FDOPA. We conclude that FDOPA is accurate as a surrogate for MET in imaging amino
      acid transport in malignant cerebral lesions for the purpose of visualisation of
      vital tumour tissue. It combines the good physical properties of (18)F with the
      pharmacological properties of MET and might therefore be a valuable PET
      radiopharmaceutical in brain tumour imaging.

PMID- 14579098
TI  - FDG-PET in infectious and inflammatory disease.

PMID- 14579099
TI  - FDG-PET in infectious and inflammatory disease.

PMID- 14579100
TI  - From PET detectors to PET scanners.
AB  - This review describes the properties of available and emerging radiation detector
      and read-out technologies and discusses how they may affect PET scanner
      performance. After a general introduction, there is a section in which the
      physical properties of several different detector scintillators are compared.
      This is followed by a discussion of recent advances in read-out electronics.
      Finally, the physical performance of the several commercial PET scanners is
      summarized.

PMID- 14579103
TI  - Use of co-registered 11C-methionine PET and computed tomography for the
      localisation of parathyroid adenomas.

PMID- 14579101
TI  - Individual measurements may not closely follow average tendencies: the paradigm
      of nuclear cardiology.

PMID- 14579104
TI  - Duplication of the scapula.
AB  - Only three cases of scapular duplication have been described in English in the
      literature. We report a case of a child with duplication of the right scapula,
      operated on at our center with good results.

PMID- 14579106
TI  - An approximate estimate of the ion-activity product of calcium oxalate in rat
      urine.
AB  - The objective of this report was to derive a simplified approximate estimate of
      the ion-activity product of calcium oxalate (AP(CaOx)) in rat urine. The relative
      effect of each urine variable was assessed by means of iterative computerised
      approximation with the EQUIL2 program. A basic urine composition was chosen from
      literature and experimental data. The most pronounced influence on AP(CaOx )was
      recorded for urinary calcium, oxalate, citrate, magnesium and volume. Based on
      these calculations, an AP(CaOx) index(RAT) was formulated: [formula; see text].
      For a 24-h urine sample, factor A takes the value 4067 and factor F should be set
      to 0.015. Conclusion. A simplified approximate estimate of AP(CaOx) was derived
      for rat urine. There was a reasonably good correspondence between AP(CaOx)
      index(RAT) and AP(CaOx), as derived from EQUIL2 ( r=0.890), provided the other
      urine variables do not deviate very much from that in the basic composition.

PMID- 14579107
TI  - Long-term use of sertraline leads to alterations in contractility of rat isolated
      vas deferens.
AB  - Previous experiments with rat isolated vas deferens have shown that sertraline
      pretreatment inhibits contractile responses to noradrenaline, KCl, serotonin and
      electrical field stimulation. In the present study, the aim was to investigate
      the effects of long-term use of sertraline on contractile responses of rat
      isolated vas deferens. Fifteen Sprague-Dawley rats were given long-term (21 days)
      sertraline treatment, while another 15 were used as control. Both vas deferens
      were excised. Epididymal and prostatic segments of each underwent electrical
      field and chemical stimulation (noradrenaline, serotonin, acetylcholine,
      adenosine-triphosphate). Epididymal and prostatic segments had different
      contraction characteristics. Long-term sertraline treatment inhibited contractile
      responses of vas deferens segments to electrical field stimulation. The responses
      to noradrenaline were amplified with a left shift on both segments. Responses to
      serotonin had only a left shift on epididymal segments, while no contractile
      responses were observed on prostatic segments of the groups. Long-term treatment
      with sertraline had peripheral effects on rat vas deferens contractility, and
      some of the effects may be through mechanisms other than the inhibition of
      serotonin re-uptake.

PMID- 14579105
TI  - Terminal deoxynucleotidyl transferases from elasmobranchs reveal structural
      conservation within vertebrates.
AB  - The DNA polymerase (pol) X family is an ancient group of enzymes that function in
      DNA replication and repair (pol beta), translesion synthesis (pol lambda and pol
      micro) and terminal addition of non-templated nucleotides. This latter terminal
      deoxynucleotidyl transferase (TdT) activity performs the unique function of
      providing diversity at coding joins of immunoglobulin and T-cell receptor genes.
      The first isolated full-length TdT genes from shark and skate are reported here.
      Comparisons with the three-dimensional structure of mouse TdT indicate structural
      similarity with elasmobranch orthologues that supports both a template
      independent mode of replication and a lack of strong nucleotide bias. The
      vertebrate TdTs appear more closely related to pol micro and fungal polymerases
      than to pol lambda and pol beta. Thus, unlike other molecules of adaptive
      immunity, TdT is a member of an ancient gene family with a clear gene phylogeny
      and a high degree of similarity, which implies the existence of TdT ancestors in
      jawless fishes and invertebrates.

PMID- 14579109
TI  - Unilateral spermatic cord torsion without ipsilateral spermatogenetic material:
      effects on testicular blood flow and fertility potential.
AB  - This experiment was planned to answer the question of how the elimination of
      ipsilateral spermatogenetic material, which is necessary for contralateral
      testicular damage caused by an autoimmune response, affects contralateral
      testicular blood flow and fertility potential in unilateral spermatic cord
      torsion (USCT). Thirty-four male and 68 female adult albino rats were divided
      into three groups. Group 1 rats underwent a control operation, group 2 rats
      underwent subepididymal orchiectomy to eliminate spermatogenetic material, and
      group 3 rats underwent USCT after subepididymal orchiectomy. Testicular blood
      flows of the rats were measured by (133)Xe clearance technique. Additionally, to
      determine fertility potential, each male rat was housed with two female rats.
      Numbers of impregnated and delivered rats were recorded. Both mean testicular
      blood flow and fecundity of group 3 were significantly lower than those of groups
      1 and 2. When compared with groups 1 and 2, fertility and mean number of the
      impregnated rats of group 3 were lower but the differences were not significant.
      These findings suggest that absence of spermatogenetic material in USCT reduces
      contralateral blood flow and fertility potential. Therefore, contralateral
      testicular damage originating from blood flow alterations rather than autoimmune
      mechanism should be considered to explain fertility problems encountered
      following USCT.

PMID- 14579108
TI  - Significance of apoptosis in metastasizing testis tumors.
AB  - Testis tumors of embryonal origin (ten metastasized, six non-metastasized) and 17
      mixed testis cell carcinomas (eight metastasized, nine non-metastasized) were
      examined. A triple immunofluorescence microscopic labeling procedure allowed the
      simultaneous detection of two features of apoptosis, namely morphological changes
      in the nucleus (DNA condensation visualized by DAPI staining) and the process of
      DNA fragmentation (TdT-assay) in tumor cells as well as T-cells (recognized by
      their CD45RO epitope). Both methods for apoptosis detection showed similar
      apoptotic indices (AI) only in 2.6% of all tumors. Most tumors (81.6%) showed
      more cells with DNA fragments than condensed chromatin, but in a number of cases
      (10.5%) the opposite pattern was found. These data add to the few published in
      vivo examinations of apoptosis using different methods and help to explain
      differences in the judgment of apoptosis significance for tumor prognosis. With
      regard to tumorigenesis, non-metastasized testis tumors were characterized by
      higher AIs of tumor cells and T-cells compared with metastasized tumors, which
      could be interpreted as a characteristic of tumors in an earlier stage of their
      development into an apoptosis-resistant phenotype. For the first time, in
      metastasized tumors a 5 to 25-fold increase of the T-cell's AIs over the
      corresponding AIs of tumor cells was shown. This suggests a successful
      counterattack of tumor cells, thus supporting the process of metastasis. However,
      only ten out of 33 tumors revealed these AI changes, which again highlights that
      tumor biology cannot be predicted by a single parametric approach. It remains to
      be seen whether these characteristics might be suitable for a reliable prediction
      of metastasis.

PMID- 14579110
TI  - Is haemosiderin visible indefinitely on gradient-echo MRI following traumatic
      intracerebral haemorrhage?
AB  - Gradient-echo (GE) MRI has been demonstrated to be the most sensitive current
      technique for detection of intracerebral haemosiderin, especially in the chronic
      stage of haemorrhage. Our purpose was to see whether GE MRI shows old haemorrhage
      indefinitely. We reviewed serial GE images of 105 adults with imaging features
      consistent with post-traumatic intracerebral haemorrhage, who had serial MRI at
      1, 4-6, 12, and 24 months after trauma. Of 1235 scattered low-signal foci
      consistent with isolated intracerebral haemosiderin deposits on images at 4-6
      months, 248 (20.1%) were not seen at 24-month assessment. Reviewing individual
      patients, we saw that in 71.8% of those with scattered haemosiderin deposits and
      46.4% of those with haemosiderin surrounded by gliosis, the low-signal foci
      appeared less conspicuous with time. Even given certain limitations to the
      interpretation of these findings, it would appear that, even with the use of GE
      MRI, time affects the visibility of haemorrhagic intracerebral lesions. We
      therefore conclude that a time of 4-6 months to 1 year or slightly more should be
      recommended for most precise detection of haemosiderin deposits on MRI of head
      injured patients, should this be thought desirable. Normal GE images may not
      exclude old haemorrhage.

PMID- 14579111
TI  - Identification of a non-selective cation channel current in myometrial cells
      isolated from pregnant rats.
AB  - Non-selective cation channel (NSCC) currents were identified in myometrial smooth
      muscle cells isolated from pregnant rats (day 18-20) using the whole-cell patch
      clamp method. NSCC currents had a linear current/voltage relationship and were
      time independent. Reduction of extracellular Na(+) substantially decreased the
      amplitude of NSCC currents, indicating that the NSCC is permeable to Na(+). NSCC
      currents were blocked by La(3+) and Gd(3+) with K(d) values of 2.2 and 1.0 micro
      M, respectively. The relative permeability of various monovalent cations for NSCC
      was estimated by measurement of the reversal potential. The relative permeability
      for K(+):Cs(+):Na(+):Li(+) was 1.3:1:0.9:0.8. NSCC also had a small, but
      detectable, permeability for Ca(2+). Extracellular Mg(2+) inhibited myometrial
      NSCC currents concentration dependently with a K(d) of 0.28 mM. The observed
      Mg(2+) block may reasonably explain the inhibitory effect of magnesium on uterine
      contractions in the treatment of pre-term labor. Our results suggest that the
      NSCC plays a role in the regulation of myometrial contractility.

PMID- 14579112
TI  - Optical mapping of the spread of excitation in the isolated rat atrium during
      tachycardia-like excitation.
AB  - Multiple-site optical recording of membrane potential activity, using the voltage
      sensitive merocyanine-rhodanine dye NK2761 and a multiple-element photodiode
      array, was employed to monitor action potentials in an isolated rat atrial
      preparation. The events of tachycardia-like excitation (TE) were evoked by
      electrical stimulation. The conduction pattern of excitation was assessed
      optically by timing the feet of optical action potentials, then maps of
      excitation spread patterns were made. The excitatory waves often rotated around
      the blocked area including the ostium of the superior vena cava. Other patterns,
      such as reentry without anatomical obstacles, ectopic pacemaker and more complex
      patterns, were sometimes observed. Optical mapping during the initiation phase of
      TE indicated that the decrease of the conduction velocity and the appearance of
      blocked areas contributed the establishment of TE. On the basis of the
      characteristics of TE, it is suggested that TE is a metastable state of atrial
      rhythm. TE appears to be analogous to atrial flutter.

PMID- 14579113
TI  - Organic anion transporting polypeptides of the OATP/ SLC21 family: phylogenetic
      classification as OATP/ SLCO superfamily, new nomenclature and
      molecular/functional properties.
AB  - The organic anion transporting polypeptides (rodents: Oatps, human: OATPs) form a
      superfamily of sodium-independent transport systems that mediate the
      transmembrane transport of a wide range of amphipathic endogenous and exogenous
      organic compounds. Since the traditional SLC21 gene classification does not
      permit an unequivocal and species-independent identification of genes and gene
      products, all Oatps/OATPs are newly classified within the OATP/ SLCO superfamily
      and subdivided into families (>/=40% amino acid sequence identity), subfamilies
      (>/=60% amino acid sequence identity) and individual genes and gene products
      according to their phylogenetic relationships and chronology of identification.
      Implementation of this new classification and nomenclature system occurs in
      agreement with the HUGO Gene Nomenclature Committee (HGNC). Among 52 members of
      the OATP/ SLCO superfamily, 36 members have been identified so far in humans, rat
      and mouse. The latter are clustered within 6 (out of 12) families (OATP1-OATP6)
      and 13 subfamilies. Oatps/OATPs represent 12 transmembrane domain proteins and
      contain the superfamily signature D-X-RW-(I,V)-GAWW-X-G-(F,L)-L. Although species
      divergence, multispecificity and wide tissue distribution are common
      characteristics of many Oatps/OATPs, some members of the OATP/ SLCO superfamily
      are highly conserved during evolution, have a high substrate specificity and
      exhibit unique cellular expression in distinct organs. Hence, while Oatps/OATPs
      with broad substrate specificity appear to play an important role in the
      bioavailability, distribution and excretion of numerous exogenous amphipathic
      organic anionic compounds, Oatps/OATPs with a narrow spectrum of transport
      substrates may exhibit more specific physiological functions in distinct organs.

PMID- 14579114
TI  - Effects of electrostimulation on glycogenolysis in cultured rat myotubes.
AB  - A model for electrostimulation causing contractions of primary cultures of rat
      myotubes was established. The kinetics of glycogen degradation was investigated
      for a 2-h period to elucidate the coupling between contraction and glycogenolytic
      flux. Electrostimulation caused contraction and increased glycogenolytic flux,
      but had no effect on glycogen phosphorylase-a activity. Forskolin increased
      glycogenolytic flux more than electrostimulation, and caused a fast activation of
      glycogen phosphorylase, while it did not elicit contraction. The effects of
      electrostimulation and forskolin on glycogenolytic flux were partly additive. The
      metabolism of glucose and glycogen was almost equally anaerobic and aerobic. The
      ATP content remained constant during glycogenolysis, but phosphocreatine
      decreased with the largest decrease in electrostimulated cells. The calculated
      ATP turnover rate increased about 3 times by electrostimulation. For all
      conditions, pHi decreased from about 7.0 to about 6.6 at 2 h. It is concluded
      that in the present in vitro system glycogenolytic flux may be enhanced without
      eliciting contraction, a condition normally not observed in vivo. The system also
      shows much less dynamic range of energy metabolism than in vivo, primarily
      because of a high resting ATP turnover.

PMID- 14579115
TI  - Polarisation of T-cadherin to the leading edge of migrating vascular cells in
      vitro: a function in vascular cell motility?
AB  - Both histological and in vitro studies indicate a relationship between T-cadherin
      levels and acquisition of a modulated, migratory phenotype by vascular cells.
      This study further examines a role for T-cadherin in relation to cell migration
      and adhesion. Fluorescence microscopic examination of T-cadherin localisation in
      confluent cultures of human umbilical vein endothelial cells (HUVEC), human
      aortic smooth muscle cells and the human carcinoma cell line ECV-304 revealed
      global distribution over the entire cell body, and with only slight enrichment at
      cell borders. This contrasts with restricted cell-cell junction localisation of
      classical cadherin (for example, VE-cadherin in HUVEC). In wounded cultures, T
      cadherin polarised to the leading edge of cells migrating into the wound area,
      again contrasting with classical VE-cadherin, which was undetectable in this
      region. Confocal microscopy demonstrated that potential signalling functions of T
      cadherin at the leading edge are unrelated to physical interactions with
      caveolin. Adherence of HUVEC onto a monolayer of T-cadherin-transfected L929
      cells is significantly reduced compared with adhesion onto control (T-cadherin
      negative) L929. Thus T-cadherin is not required for maintenance of intercellular
      adhesion, but may rather function as a signalling molecule involved in cell-cell
      recognition and sensing of the environment in processes where cell detachment
      occurs.

PMID- 14579116
TI  - Magnetic resonance imaging of unilateral lacrimal gland lesions.
AB  - PURPOSE: To report the findings on magnetic resonance imaging (MRI) of various
      benign and malignant unilateral lacrimal gland lesions. METHODS: This is a
      retrospective noncomparative interventional case series. Thirty-one consecutive
      patients with a unilateral lacrimal gland lesion were analyzed. The preoperative
      MRI findings were correlated with the pathology results. The main outcome
      measures were anatomic extent, configuration, margins, angulation, internal
      features on T1- and T2-weighted images (with respect to extraocular muscles and
      cerebral gray matter), contrast enhancement of the lesion and adjacent bone
      change on MRI. RESULTS: Of the 31 patients, 21 had chronic dacryoadenitis, 3 had
      lymphoid tumors, and 7 had epithelial tumors including pleomorphic adenoma (3),
      adenoid cystic carcinoma (3), and pleomorphic adenocarcinoma (1). The results of
      the patients with chronic dacryoadenitis demonstrated involvement of the orbital
      lobe alone in 13 patients (62%), involvement of both orbital and palpebral lobes
      in 8 (38%), a molded configuration with ill-defined margins, sharp angles in 13
      (62%), round angles in 8 (38%), lack of bone change, an isointense internal
      signal on T1-weighted images, a hypointense signal on T2-weighted images, and
      moderate contrast enhancement. The patients with lymphoid tumors demonstrated
      involvement of the orbital lobe, a molded configuration with ill-defined margins
      and sharp angles, lack of bone change, an isointense internal signal on T1
      weighted images, an isointense signal on T2-weighted images, and moderate
      contrast enhancement. Those with epithelial tumors showed involvement of the
      orbital lobe, a well-circumscribed oval configuration, and round angles.
      Pleomorphic adenoma demonstrated smooth margins, bone expansion in two patients,
      and no bone change in one. Adenoid cystic carcinoma and pleomorphic
      adenocarcinoma showed irregular margins and bone destruction. All epithelial
      tumors demonstrated an isointense internal signal on T1-weighted images, a
      hyperintense signal on T2-weighted images, and moderate contrast enhancement.
      CONCLUSIONS: It is difficult to uniformly correlate the MRI features and
      histopathologic findings in lacrimal gland lesions. However, MRI seems to be
      useful in determining the etiology of a unilateral lacrimal gland lesion.
      Internal tissue features on T1- and T2-weighted images of MRI are most helpful in
      categorizing these lesions. Although the number of patients is small, our
      findings suggest that there are differences in orbital MRI findings of
      inflammatory lesions and lymphoid tumors as compared to benign and malignant
      epithelial tumors in the lacrimal gland fossa.

PMID- 14579118
TI  - Familial Parkinson's disease: a hint to elucidate the mechanisms of nigral
      degeneration.
AB  - In the majority of patients with Parkinson's disease (PD), it is now clear that
      genetic factors contribute to the pathogenesis of PD, although the contribution
      of genetic and environmental factors remains to be elucidated. The contribution
      of genetic factors to the pathogenesis of PD is supported by the demonstration of
      the high concordance in twins, increased risk among relatives of PD patients in
      case control and family studies, and the existence of familial PD based on single
      gene defects. Recently, several genes have been mapped and identified in patients
      with familial PD (FPD). alpha-Synuclein is involved in a rare dominant form of
      familial PD with dopa responsive parkinsonian features and Lewy body positive
      pathology. In contrast, parkin is responsible for autosomal recessive form of
      earlyonset PD with Lewy body-negative pathology. This form is identified with
      world-wide distribution among patients with young-onset PD. Furthermore,
      ubiquitin carboxy terminal hydrolase L1 (UCHL1) gene is responsible for an
      autosomal dominant form of typical PD, although only a single family has so far
      been identified with a mutation of this gene. In addition, DJ-1 has been
      identified as a causative gene for PARK7, a recessive form of familial PD. Now, a
      total of five causative genes including NR4A2 have been identified, and others
      such as PARK3, -4, -6, -8, -9, -10 have been mapped as hereditary forms of
      familial PD. The presence of different loci or different causative genes
      indicates that PD is not a single entity but a highly heterogeneous disorder.
      However, the functions of causative genes may share a common pathway such as an
      ubiquitin-proteasome pathway. Thus, identification and elucidation of the
      causative genes should enhance our understanding of the pathogenesis of not only
      familial PD, but also sporadic PD.

PMID- 14579119
TI  - Aggregation of alpha-synuclein in the pathogenesis of Parkinson's disease.
AB  - Lewy bodies (LBs) are hallmark lesions in the brains of patients with Parkinson's
      disease (PD) and dementia with Lewy bodies (DLB). By raising a monoclonal
      antibody LB509 against purified LBs from the brains of patients with DLB that
      strongly immuola-beled LBs, we found that alpha-synuclein is one of the major
      components of LBs. Thus, the deposition of alpha-synuclein, an abundant
      presynaptic brain protein, as fibrillary aggregates in affected neurons or glial
      cells,was highlighted as a hallmark lesion of a subset of neurodegenerative
      disorders, including PD, DLB and multiple system atrophy collectively referred to
      as synucleinopathies. Importantly, the identification of missense mutations in
      alpha-synuclein gene in some pedigrees of familial PD has strongly implicated
      alpha-synuclein in the pathogenesis of PD and other synucleinopathies. We then
      examined the specific post-translational modifications that characterize and
      underlie the aggregation of alpha-synuclein in synucleinopathy brains by mass
      spectrometry and using a s pecific antibody,and found that serine 129 of alpha
      synuclein deposited in synucleinopathy lesions is selectively and extensively
      phosphorylated. These findings underscore the importance of phosphorylation of
      filamentous proteins in the pathogenesis of neurodegenerative disorders.

PMID- 14579120
TI  - New insights into Parkinson's disease.
AB  - Parkinson's disease (PD) is the most common neurodegenerative movement disorder.
      Recent advances in genetics and pathophysiology have led to new insights into the
      pathogenesis of PD. Ten loci have been linked to hereditary PD. Mutations in
      alpha-synuclein and ubiquitin carboxy hydrolase L1 (UchL1) cause autosomal
      dominant PD and mutations in parkin and DJ-1 cause autosomal recessive PD. alpha
      Synuclein has emerged as an important protein in the pathogenesis of PD, as it
      appears to be the major structural component of Lewy bodies and its
      accumulation/aggregation seems to play a prominent role in sporadic PD. Mutations
      in parkin are the most common cause of hereditary PD, and mutations in parkin are
      thought to lead to a loss of parkin's ubiquitin E3 ligase activity. Derangements
      in parkin function as well as mutations in UCH-L1 fit with the notion that
      derangements in the ubiquitin proteasomal pathway (UPP) may play important roles
      in the demise of dopamine neurons in PD. DJ-1 is a protein of unknown function
      that is linked to autosomal recessive PD. Oxidative stress and impairment in
      mitochondrial complex I activity are important in sporadic PD, and there is
      emerging interest in the role of herbicides, fungicides and insecticides that
      inhibit mitochondrial complex I activity and their role in contributing to the
      development of PD. These important findings serve as the foundation for
      discovering new pathways that may lead to the development of new therapies for
      PD.

PMID- 14579121
TI  - Pael receptor, endoplasmic reticulum stress, and Parkinson's disease.
AB  - Autosomal recessive juvenile parkinsonism (AR-JP) is caused by mutations of the
      parkin gene. Parkin is an E3 ubiquitin ligase that specifically recognizes its
      substrate protein, promoting its ubiquitination and subsequent degradation.
      Accordingly, we hypothesized that AR-JP may be caused by accumulation of an
      unidentified neurotoxic protein, which is a substrate of parkin. Based on this
      hypothesis, we cloned parkin-binding protein using a yeast two-hybrid system and
      identified a putative G protein-coupled receptor protein,which we named the Pael
      receptor (Pael-R). When overexpressed in cells, this receptor became unfolded,
      insoluble, and ubiquitinated. Accumulation of the insoluble Pael-R subsequently
      led to endoplasmic reticulum (ER) stress-induced cell death. Parkin specifically
      ubiquitinates the unfolded Pael-R and promotes its degradation, resulting in
      suppression of cell death induced by the accumulation of unfolded Pael-R.
      Moreover, insoluble Pael-R accumulates in the brains of AR-JP patients. It is
      highly expressed by the dopaminergic neurons of the substantia nigra, strongly
      suggesting that accumulation of unfolded Pael-R may lead to selective death of
      dopaminergic neurons in AR-JP.Recently, we identified Hsp70 and its co-chaperone
      CHIP as novel parkin-binding partners. We found that CHIP enhanced parkinmediated
      ubiquitination of Pael-R. In concert with Hsp70, CHIP also enhanced the ability
      of parkin to inhibit cell death induced by Pael-R, indicating that CHIP and Hsp70
      are both co-factors of parkin.

PMID- 14579122
TI  - Environmental, life-style, and physical precursors of clinical Parkinson's
      disease: recent findings from the Honolulu-Asia Aging Study.
AB  - BACKGROUND: Increased westernization with Japanese migration to the U. S. in the
      early 20(th) century is thought to have altered the risk of cardiovascular
      disease. Whether similar effects include changes in the risk of Parkinson's
      disease (PD) is not clear. This report describes the relations between
      environmental, life-style, and physical attributes and the incidence of PD that
      have been observed in the Honolulu-Asia Aging Study. METHODS: Beginning in 1965,
      environmental, life-style, and physical attributes were recorded at selected
      examinations in a cohort of 8,006 Japanese-American men. Subjects were followed
      for clinical PD. FINDINGS: During 30 years of follow- up, PD was observed in 137
      men. Overall incidence (7.1/10,000 person-years) was generally higher than in
      Asia and similar to rates observed in Europe and the U. S. Precursors of PD
      included constipation, adiposity, years worked on a sugar or pineapple
      plantation, years of exposure to pesticides, and exposure to sugar cane
      processing. Factors showing an inverse association with PD included coffee intake
      and cigarette smoking. Among dietary factors, carbohydrates increased the risk of
      PD while the intake of polyunsaturated fats appeared protective. Total caloric
      intake, saturated and monounsaturated fats, protein, niacin, riboflavin, beta
      carotene, vitamins A, B, and C, dietary cholesterol, cobalamin, alpha-tocopherol,
      and pantothenic acid showed no clear relation with clinical PD. INTERPRETATION:
      Findings suggest that several environmental, life-style, and physical attributes
      appear to be precursors of PD. Whether patterns of precursors can be used to
      identify individuals at high risk of future PD or can broaden the scope of early
      interventions or recruitment into neuroprotective trials warrants further study.

PMID- 14579123
TI  - Toward identification of susceptibility genes for sporadic Parkinson's disease.
AB  - To identify susceptibility genes for Parkinson's disease (PD) and to establish
      tailor-made medicine for PD, we studied 20 single nucleotide polymorphisms (SNPs)
      in 18 candidate genes for association with PD. We found that homozygosity for the
      V66M polymorphism of the BDNF gene occurs more frequently in PD patients than in
      unaffected controls and confirmed an association with the S18Y polymorphism of
      the UCHL1 gene. We further started microsatellite marker-based genome-wide
      association studies by using the pooled DNA method. We have finished checking
      approximately 6800 markers and found some significant associations (p=3.9 x 10(
      6)) on chromosome 1 where other studies showed a linkage. Genes in linkage
      disequilibrium with these markers may be associated with pathogenesis of PD.

PMID- 14579124
TI  - Do patients with Parkinson's disease benefit from embryonic dopamine cell
      transplantation?
AB  - Embryonic dopamine cell transplants survive in nearly all patients regardless of
      age and without immunosuppression. Transplants can improve Parkinson "off"
      symptoms up to the best effects of L-dopa observed preoperatively. They cannot
      improve the "best on" state. Transplants appear to survive indefinitely. In 10 to
      15% of patients, transplants can reproduce the dyskinetic effects of L-dopa even
      after discontinuing all L-dopa. Neurotransplantation should be tried earlier in
      the clinical course of Parkinson's to see if earlier intervention can prevent
      progression of the disease, particularly the dyskinetic responses seen after
      longterm L-dopa treatment.

PMID- 14579125
TI  - Does transcranial magnetic stimulation improve the motor symptoms of Parkinson
      disease?
AB  - Repetitive transcranial magnetic stimulation (rTMS) has been used as a potential
      therapeutic tool in various neurological and psychiatric disorders. We reviewed
      the effects of rTMS as a treatment of Parkinson disease in this paper. The
      existing reports have been conflicting regarding the efficacy of the rTMS in PD.
      The controversy arises from the differences of the stimulation parameters and
      evaluation methods of the effects in those studies. Furthermore, placebo effects
      are common in trials of therapy for PD. The Japanese multi-center, double
      blinded, sham stimulation controlled trial showed an efficacy in both the rTMS
      treated and control patients. The stimulation parameters used in this trial
      showed some efficacy; however, the degree of the effects were not significantly
      different from randomized, controlled patients. The result does not prove the
      efficacy of the rTMS; on the other hand, it does not rule out the efficacy.
      Further trials are necessary to reveal the therapeutic effect of rTMS in PD.
      Further studies should be performed aiming to reveal the optimal stimulation
      parameters.

PMID- 14579126
TI  - The MSL complex levels are critical for its correct targeting to the chromosomes
      in Drosophila melanogaster.
AB  - In Drosophila, dosage compensation requires assembly of the Male Specific Lethal
      (MSL) protein complex for doubling transcription of most X-linked genes in males.
      The recognition of the X chromosome by the MSL complex has been suggested to
      include initial assembly at approximately 35 chromatin entry sites and subsequent
      spreading of mature complexes in cis to numerous additional sites along the
      chromosome. To understand this process further we examined MSL patterns in a
      range of wild-type and mutant backgrounds producing different amounts of MSL
      components. Our data support a model in which MSL complex binding to the X is
      directed by a hierarchy of target sites that display different affinities for the
      MSL proteins. Chromatin entry sites differ in their ability to provide local
      intensive binding of complexes to adjacent regions, and need high MSL complex
      titers to achieve this. We also mapped a set of definite autosomal regions
      (approximately 70) competent to associate with the functional MSL complex in wild
      type males. Overexpression of both MSL1 and MSL2 stabilizes this binding and
      results in inappropriate MSL binding to the chromocenter and the 4th chromosome.
      Thus, wild-type MSL complex titers are critical for correct targeting to the X
      chromosome.

PMID- 14579127
TI  - Rearrangements of ribosomal DNA clusters in late generation telomerase-deficient
      Arabidopsis.
AB  - The ends of eukaryotic chromosomes are capped with special nucleoprotein
      structures called telomeres. Telomere shortening due to telomerase inactivation
      may result in fusion of homologous or heterologous chromosomes, leading to their
      successive breakage during anaphase movement, followed by fusion of broken ends
      in the next cell cycle, i.e. the breakage-fusion-bridge (BFB) cycle. Using
      fluorescence in situ hybridization (FISH) with 25S rDNA and specific bacterial
      artificial chromosome (BAC) probes we demonstrate participation of chromosomes 2
      and 4 of Arabidopsis thaliana AtTERT null plants in the formation of anaphase
      bridges. Both homologous and non-homologous chromosomes formed transient anaphase
      bridges whose breakage and unequal separation led to genome rearrangement,
      including non-reciprocal translocations and aneuploidy. The 45S rDNA regions
      located at the ends of chromosomes 2 and 4 were observed in chromosome bridges at
      a frequency approximately ten times higher than expected in the case of random
      fusion events. This outcome could result from a functional association of rDNA
      repeats at nucleoli. We also describe increased variation in the number of
      nucleoli in some interphase cells with supernumerary rDNA FISH signals. These
      data indicate that dysfunctional telomeres in Arabidopsis lead to massive genome
      instability, which is induced by multiple rounds of the BFB mechanism.

PMID- 14579128
TI  - PLU-1, a transcriptional repressor and putative testis-cancer antigen, has a
      specific expression and localisation pattern during meiosis.
AB  - PLU-1, a large multi-domain nuclear protein with strong transcriptional
      repression activity, is a member of the ARID family of DNA binding proteins. In
      previous studies, high levels of expression of Plu-1 mRNA and PLU-1 protein were
      detected in breast cancers, while expression in normal adult tissues was detected
      only in the testis, ovary and transiently in the mammary gland of the pregnant
      female. Due to its high levels of expression in the testis and to its specific
      relationship to cancer, PLU-1 has been proposed to belong to the family of testis
      cancer antigens. In this study we attempted to determine putative functions for
      PLU-1 during spermatogenesis. To address this, we analysed the pattern of
      expression and localisation of this protein in mouse testicular cells during
      postnatal development and adulthood. Using in situ hybridisation and
      immunostaining of testis sections we show that Plu-1 mRNA and PLU-1 protein are
      both highly expressed in the mitotic spermatogonia. Expression is reduced
      dramatically in the early prophase I stages (zygotene, leptotene), but reappears
      at pachytene and is still detectable in diplotene cells. We also found that PLU-1
      localises diffusely over the nucleus, which indicates a potential chromatin
      binding ability of this protein. Consistent with this notion, we found that PLU-1
      is present in the chromatin fraction in biochemical cell fractionation
      experiments using both somatic and meiotic cells. Our data point to a role for
      PLU-1 in meiotic transcription, which may be restricted to certain meiotic stages
      and may be mediated by the ability of this protein to associate with the
      chromatin.

PMID- 14579129
TI  - The ThioredoxinT and deadhead gene pair encode testis- and ovary-specific
      thioredoxins in Drosophila melanogaster.
AB  - So far, two thioredoxin proteins, DHD and Trx-2, have been biochemically
      characterized in Drosophila melanogaster. Here, with the cloning and
      characterization of TrxT we describe an additional thioredoxin with testis
      specific expression. TrxT and dhd are arranged as a gene pair, transcribed in
      opposite directions and sharing a 471 bp regulatory region. We show that this
      regulatory region is sufficient for correct expression of the two genes. This
      gene pair makes a good model for unraveling how closely spaced promoters are
      differentially regulated by a short common control region. Both TrxT and DHD
      proteins are localized within the nuclei in testes and ovaries, respectively. Use
      of a transgenic construct expressing TrxT fused to Enhanced Yellow Fluorescent
      Protein reveals a clear association of TrxT with the Y chromosome lampbrush loops
      ks-1 and kl-5 in primary spermatocytes. The association is lost in the absence of
      the Y chromosome. Our results suggest that nuclear thioredoxins may have
      regulatory functions in the germline.

PMID- 14579130
TI  - Analysis of the amplification and transcription of the C3-22 gene of
      Rhynchosciara americana (Diptera: Sciaridae) in transgenic lines of Drosophila
      melanogaster.
AB  - Drosophila melanogaster was transformed with an 18 kb fragment of the C3 DNA puff
      of Rhynchosciara americana, including the C3-22 gene and the origins of
      replication that direct amplification. Different tissues and developmental stages
      of five independent transgenic lines were analyzed by quantitative Southern blot
      hybridization. No indication was found that the transformed fragment was
      amplified, strongly suggesting that factors involved in DNA puff amplification
      have not been conserved in Drosophila. Transcription of the C3-22 gene in the
      transgenic lines was found to be at a low and constitutive level throughout
      development. These results indicate that, unlike other DNA puff genes, the
      factors that regulate the C3-22 gene are not conserved in Drosophila.

PMID- 14579131
TI  - Sequence subfamilies of satellite repeats related to rDNA intergenic spacer are
      differentially amplified on Vicia sativa chromosomes.
AB  - We cloned and sequenced the Vicia sativa 25S-18S rDNA intergenic spacer (IGS) and
      the satellite repeat S12, thought to be related to the spacer sequence. The
      spacer was shown to contain three types of subrepeats (A, B, and C) with monomers
      of 173 bp (A), 10 bp (B), and 66 bp (C), separated by unique or partially
      duplicated sequences. Two spacer variants were detected in V. sativa that
      differed in length (2990 and 3168 bp) owing to an extra copy of the subrepeat A.
      The A subrepeats were also shown to be highly homologous to the satellite repeat
      S12, which is located in large clusters on chromosomes 4, 5, and 6, and is not
      associated with the rDNA loci. Sequencing of additional S12 clones retrieved from
      a shotgun genomic library allowed definition of three subfamilies of this repeat
      based on minor differences in their nucleotide sequences. Two of these
      subfamilies could be discriminated from the rest of the S12 sequences as well as
      from the IGS A subrepeats using specific oligonucleotide primers that labeled
      only a subset of the S12 loci when used in the primed in situ DNA labeling
      (PRINS) reaction on mitotic chromosomes. These experiments showed that, in spite
      of the high overall similarity of the IGS A subrepeats and the S12 satellite
      repeats, there are S12 subfamilies that are divergent from the common consensus
      and are present at only some of the chromosomes containing the S12 loci. Thus,
      the subfamilies may have evolved at these loci following the spreading of the A
      subrepeats from the IGS to genomic regions outside the rDNA clusters.

PMID- 14579132
TI  - Radioactive contamination of bottom sediments in the upper reaches of the Techa
      river: analysis of the data obtained in 1950 and 1951.
AB  - A stationary sorption model has been developed for re-evaluating and analysing
      archive data from 1950-1951 on the radioactive contamination of Techa river
      bottom sediments close to the site of liquid radioactive waste discharge. In
      general, good agreement was obtained between calculations and measurements, which
      substantiates further the assumptions and conclusions in two preceding articles,
      on the radionuclide composition of discharged liquid radioactive waste. Estimates
      on the effective liquid radioactive waste discharges given here are significantly
      different from those deduced in the 1950s, i.e. in summer 1950 and October 1951.
      The results are discussed in relation to the Techa River Dosimetry System 2000
      (TRDS-2000) that has recently been presented to serve as a means for estimating
      doses to the Techa river residents. Parameter values describing the exponential
      decrease of bottom sediment contamination along the river due to short-lived
      radionuclides, such as (106)Ru, and (144)Ce, agree reasonably with those used in
      TRDS-2000. However, for other radionuclides, such as (95)Zr, (95)Nb, (91)Y,
      (90)Sr and (137)Cs, substantial differences are found. It is demonstrated that
      water flow rate, width of the river, and surface area of bottom sediments are
      important parameters which were not adequately taken into account in TRDS-2000.
      Also, the stirring-up of contaminated bottom sediments and their subsequent
      transport by the water flow are seen to be an important mechanism that governs
      the radionuclide transport downstream. This mechanism was not included in the
      TRDS-2000 model. It is concluded that the sorption model used in TRDS-2000 for
      the reconstruction of radioactive contamination of water and bottom sediments of
      the Techa river in 1949-1951, is subject to considerable errors. While the
      present paper is focussed on details of the dosimetric modelling, the
      implications for the Techa river dosimetry are major. They will be further
      elucidated in a forthcoming paper.

PMID- 14579133
TI  - On an evaluation of external dose values in the Techa River Dosimetry System
      (TRDS) 2000.
AB  - Absorbed doses were determined by thermoluminescence (TL) measurements for bricks
      from a height of 6 m from the south-western wall of the former mill in Metlino
      that faced the Techa river. Measurements of the internal beta-radiation and alpha
      radiation in the brick samples and of radionuclide activities in soil samples
      from the Techa river valley were performed. The absorbed dose in bricks due to
      the natural radiation was derived and subtracted from the total dose in order to
      obtain the absorbed dose in the bricks caused by anthropogenic sources. The
      results were combined with results from two previous studies. The absorbed dose
      in the bricks due to the radiation field after relocation of the Metlino
      population in 1956 was derived from dose rates in air measured in front of the
      sampling locations in 1996/1997. Based on these dose rates the dose to bricks was
      calculated by means of conversion factors from the literature. The absorbed dose
      accumulated in the bricks in the period 1949-1956 was nearly 80% of the total
      dose that had been determined by TL measurements. Previously derived conversion
      factors were applied to obtain an estimate of the gamma dose in air at the former
      shore of the Techa river. An uncertainty and sensitivity analysis was performed
      with the program package Crystal Ball. Care was taken to treat statistical and
      systematic uncertainties separately and to take parameter correlations into
      account. The resulting distribution for the gamma dose accumulated in the period
      1949-1956 at the Techa river shore has a median value of 32 Gy with a 95%
      confidence interval of 21-45 Gy. This study confirms the corresponding value of
      26.6 Gy that is used in the Techa River Dosimetry System (TRDS) 2000.

PMID- 14579134
TI  - Trans-trapezium carpo-metacarpal dislocation of the thumb.
AB  - We report a case of carpo-metacarpal dislocation associated with an isolated
      horizontal fracture of the trapezium. It is a rare lesion which is difficult to
      diagnose by standard radiography, and CT may be necessary for the diagnosis and
      correct treatment. In our case, stable osteosynthesis was achieved by internal
      screw fixation, and at follow-up there was an unrestricted, painless range of
      motion of the thumb.

PMID- 14579135
TI  - Mobility provocation radiostereometry in anterior cervical spine fusions.
AB  - This study aimed to evaluate the use of mobility-provocation radiostereometry
      (RSA) in anterior cervical spine fusions and compare the results to deformation
      studies on the same patients and plain flexion-extension radiographs. Mobility
      provocation RSA was used to evaluate anterior cervical spine fusions in 45
      patients. The motions recorded at 3 and 12 months postoperatively were compared
      to RSA measurements of deformation of the fusion over time and to plain flexion
      extension radiographs in the same patients taken 3 months postoperatively.
      Studies of rotations from right to left revealed ten cases with significant
      motion at 3 months, and three at 12 months. With motion from flexion to
      extension, ten cases showed significant motion at 3 months and three at 12
      months. In only three cases was the mobility-provocation RSA considered to add
      any information on the stability of the fusions compared to that obtained with
      the deformation studies. In 37 patients mobility-provocation radiography in
      flexion-extension using conventional technique was done to evaluate the accuracy.
      The mean difference between angular motions recorded on plain radiographs and
      rotations around the transverse axis in flexion to extension recorded with RSA
      was 1.6 degrees (range 0.04 degrees-8.04 degrees, SD 2.1 degrees). The
      corresponding 95% and 99% confidence limits for the difference between the two
      methods were 5.8 degrees and 7.2 degrees. The study showed that the use of
      mobility-provocation RSA did not add any information over that obtained by
      deformation RSA studies. Conventional radiography is too inaccurate to measure
      inducible displacement in this patient population.

PMID- 14579136
TI  - Antiemetic prescription in Italian breast cancer patients submitted to adjuvant
      chemotherapy.
AB  - GOAL: The aim of this study was to investigate if the Multinational Association
      of Supportive Care in Cancer (MASCC) antiemetic guidelines for the prevention of
      both acute and delayed emesis induced by highly-moderately emetogenic
      chemotherapy were transferred in daily clinical practice in Italy 2 years after
      their publication. PATIENTS AND METHODS: From 16 to 23 March 2000, all
      consecutive breast cancer patients referred to 87 Italian oncological centers to
      receive any cycle of adjuvant chemotherapy were monitored. MAIN RESULTS: Of 715
      evaluable patients submitted to chemotherapy, 533 received cyclophosphamide,
      methotrexate, 5-fluorouracil (CMF) and 151 anthracyclines. Patients receiving
      taxanes or other experimental therapies (31) were not considered. The MASCC
      recommended antiemetic prophylaxis against acute/delayed emesis was prescribed in
      56.3/45.9% patients. Antiemetic prophylaxis against delayed emesis was not
      prescribed to 30.6% of patients. The MASCC-recommended prescription against acute
      emesis was more frequently followed in research centers, in Northern Italy, and
      in centers with experience on antiemetic research. CONCLUSIONS: Two years after
      the publication of the MASCC antiemetic guidelines, strong discrepancies between
      these and antiemetic prescriptions in daily clinical practice in Italy were
      observed. The similarity of these results with those obtained in our previous
      drug utilization study on antiemetics, carried out before the publication of the
      MASCC guidelines, leads us to conclude that the transferability of antiemetic
      guidelines to daily clinical practice in Italy has been modest. A great effort
      should be made in Italy by the National Health Service to accelerate the process
      of implementation of antiemetic guidelines.

PMID- 14579138
TI  - Bilateral multifocal renal oncocytoma.
AB  - Renal oncocytoma is a rare benign tumor. Bilateral and multifocal renal
      oncocytoma has rarely been described in childhood. We report a 12-year-old girl
      who presented with massive left renomegaly and who was found to have bilateral
      cystic kidneys. A left nephrectomy was undertaken because of the renal
      enlargement, the radiological evidence of extensive disease, and to make a
      diagnosis. A diagnosis of multifocal oncocytoma was made after detailed
      histological examination.

PMID- 14579137
TI  - The burden of the 'RA RA' positive: survivors' and hospice patients' reflections
      on maintaining a positive attitude to serious illness.
AB  - GOALS: This article seeks to make a contribution to fostering work on the
      neglected area of research about how individuals maintain a positive outlook
      during their confrontation with serious illness. Insights are presented from both
      haematology survivors and hospice patients about the factors that hinder and
      facilitate their capacity to 'be positive'. PATIENTS AND METHODS: Open-ended
      interviews with 14 hospice patients and 12 haematology survivors on their
      construction of meaning in the face of serious illness were audio-recorded,
      transcribed verbatim and thematically analysed. The findings on the topic of
      maintaining a positive outlook are presented in this article. MAIN RESULTS:
      Although the participants affirmed the value of a positive perspective on their
      illness experience, they were critical of unwanted pressure from others to be
      positive: a phenomenon they called the 'RA RA' positive. Such pressure interfered
      with the natural process of continually having to re-negotiate a positive outlook
      through exploring the fullness of feeling, both positive and negative. The
      participants indicated that at times of relapse or worsening physical condition
      they had to cycle through a process of despair/negativity and re-adjustment
      before they were able to find the positive. The process could not be rushed and
      required freedom from an imposed pressure to be positive. CONCLUSIONS: The
      essential message is that a positive outlook cannot be imposed but requires a
      nurturing orientation that allows the expression of a full range of feelings in a
      supportive environment.

PMID- 14579139
TI  - Acute renal failure in children with idiopathic nephrotic syndrome.
AB  - Acute renal failure (ARF) is an uncommon but alarming complication of idiopathic
      nephrotic syndrome. The renal failure could be secondary to causes evident from
      the history and evaluation, such as severe intravascular volume depletion, acute
      tubular necrosis, allergic interstitial nephritis, bilateral renal vein
      thrombosis, acute pyelonephritis, or rapid progression of the original glomerular
      disease. It may be termed idiopathic if the underlying cause is undetermined. We
      present three children with idiopathic nephrotic syndrome who were admitted with
      acute renal failure. One case was due to drug-induced allergic interstitial
      nephritis. The other two were idiopathic in nature. Improvement in renal function
      occurred in the three patients over a variable period of 10 days to 4 weeks.
      After careful exclusion of well-known causes of acute renal failure, idiopathic
      acute renal failure (IARF) should be considered as a diagnostic possibility in
      these patients. The exact pathophysiology of IARF is not understood. Possible
      proposed explanations include interstitial edema, tubular obstruction, altered
      glomerular permeability, and unrecognized hypovolemia.

PMID- 14579140
TI  - Lupus vasculopathy combined with acute renal failure in lupus nephritis.
AB  - Several risk factors have been associated with the prognosis of lupus nephritis.
      However, few studies have focused on renal vascular lesions (such as thrombi due
      to immune complexes) as a prognostic factor in this disease. Here we present a
      case of systemic lupus erythematosus (SLE) in a 12-year-old girl who exhibited
      acute renal failure and severe hypertension on admission. Renal pathology
      findings included diffuse proliferative glomerulonephritis (class IVb) and lupus
      vasculopathy (LV) with immune complex deposition within glomerular capillaries
      and the preglomerular arteriolar lumen. Her clinical condition deteriorated
      rapidly, even after cyclophosphamide and methylprednisolone pulse therapy. It
      improved after 5 days of plasmapheresis and remained stable for up to 6 months
      under regular treatment. We suggest that renal biopsy performed early in SLE
      patients with renal involvement should be studied carefully for the presence of
      vascular lesions. Additionally, plasmapheresis can be considered in patients with
      LV refractory to other modalities of therapy.

PMID- 14579141
TI  - Parathyroid hormone and its fragments in children with chronic renal failure.
AB  - Parathyroid hormone (PTH) immunoradiometric assays (IRMA) exhibit cross
      reactivity between 1-84 PTH and long carboxyl-terminal-PTH (C-PTH) molecules. C
      PTH antagonizes the biological actions of 1-84 PTH and circulates in excess in
      chronic renal failure (CRF), partially explaining why supra-physiological PTH
      levels are recommended to maintain bone turnover. Furthermore, the ratio 1-84
      PTH/C-PTH may be related to bone turnover. This study characterizes the 1-84
      PTH/C-PTH ratio in children with varying severity of CRF and levels of PTH. Two
      hundred and forty-one children with CRF, managed with the aim of preventing the
      development of hyperparathyroidism, had PTH measured by 'intact' IRMA and a new
      more specific Cyclase-Activating-PTH (CAP) IRMA. C-PTH levels were calculated by
      subtracting CAP-IRMA from 'intact' IRMA. Fifty-three controls with normal renal
      function were also recruited. Mean 'intact' IRMA correlated with CAP-IRMA (
      r=0.98), but was higher ( P<0.001). The mean 1-84 PTH/C-PTH ratio was lower than
      controls in dialysis patients ( P=0.022) and those with a glomerular filtration
      rate <30 ml/min per m(2 )( P=0.033). This ratio was comparable to controls when
      the PTH level was normal, but was lower with PTH levels outside the normal range
      ( P<0.01). These data suggest that CAP-IRMA gives a more accurate assessment of
      actual PTH levels than 'intact' IRMA in CRF. Maintenance of normal PTH levels
      throughout the course of CRF permits the maintenance of a normal 1-84 PTH/C-PTH
      ratio, the clinical significance of which requires further investigation in
      children.

PMID- 14579142
TI  - ACE-inhibitors-induced metabolic acidosis in a child with nephrotic syndrome.
AB  - In recent years there has been an increase in the use of ACE inhibitors in the
      paediatric population. We describe a case of hyperchloraemic metabolic acidosis
      with hypoaldosteronism in a 4-year-old boy with nephrotic syndrome who was
      receiving ACE inhibitors.

PMID- 14579143
TI  - Change from a hard to soft diet alters the expression of insulin-like growth
      factors, their receptors, and binding proteins in association with atrophy in
      adult mouse masseter muscle.
AB  - To study the role of insulin-like growth factors (IGFs) in the atrophy of mouse
      masseter muscle in response to a change from a hard to a soft diet, we analyzed
      the amounts of mRNA and the immunolocalization for IGF-I, IGF-II, their receptors
      (IGFRs), and binding proteins (IGFBPs). Sixteen male ICR mice were fed a hard
      diet after weaning; they were divided into two groups at 6 months of age and fed
      a hard or a soft diet for 1 week. The soft diet treatment decreased masseter
      weight by 19% ( P<0.01) and the minimal diameter of masseter myofibers by 19% (
      P<0.01), verifying that a soft diet led to atrophy of mouse masseter muscle. The
      soft diet treatment induced a 30% reduction in the amount of IGF-I mRNA ( P<0.05)
      in preparations of whole masseter tissues. Immunohistochemical findings suggested
      that a reduction in the expression of IGF-I protein took place in the neural
      tissues, not in the masseter myofibers. The soft diet treatment induced a 56%
      decrease in IGF-II mRNA ( P<0.05), a 21% increase in IGFR2 mRNA ( P<0.01), and a
      38% decrease in IGFBP5 mRNA ( P<0.01). Immunohistochemical results suggested that
      these changes at the protein level occurred in the masseter myofibers. No
      significant or marked difference in the mRNA amount or immunostaining pattern for
      IGFR1, IGFBP3, IGFBP4, or IGFBP6 was found between the soft and hard diet groups.
      No IGFBP1 or IGFBP2 mRNA was detected. Thus, IGF-I, IGF-II, IGFR2, and IGFBP5
      seem to play a role in the atrophy of mouse masseter muscle in response to the
      change from a hard to a soft diet in an autocrine and/or paracrine manner.

PMID- 14579144
TI  - DNA fragmentation and detachment of enterocytes induced by anti-CD3 mAb-activated
      intraepithelial lymphocytes.
AB  - To elucidate the role of intraepithelial lymphocytes (IEL) and enterocytes in the
      defense mechanism of the small intestine, we designed experiments to stimulate
      the IEL by anti-CD3epsilon, anti-TCRalphabeta, or anti-TCRgammadelta monoclonal
      antibodies (mAbs), and to examine the subsequent changes to the enterocytes. The
      enterocytes of the duodenum and jejunum, but not of the ileum, showed massive DNA
      fragmentation 30 min after intraperitoneal injection of anti-CD3 mAb. These
      responses were also induced by anti-TCRgammadelta mAb, but not by anti
      TCRalphabeta mAb, and were completely inhibited by cyclosporin A. Nearly half of
      the enterocytes of the villi in the duodenum and jejunum were exfoliated into the
      lumen 4 h after the injection of the mAb. Administration of anti-CD3 mAb also
      induced DNA fragmentation in Fas-deficient MRL/lpr mice, indicating that the Fas
      Fas ligand system was not involved in these events. The anti-CD3 mAb treatment
      also induced massive DNA fragmentation in the intestinal epithelium of the
      duodenum and jejunum in TNF-receptor-1-deficient mice, whereas TNF-alpha induced
      only the detachment of intestinal epithelium of wild-type mice, implying the
      dissociation of two independent factors and/or mechanisms for DNA fragmentation
      and the subsequent epithelial cell detachment in the murine duodenum and jejunum.
      The mAb failed to exfoliate the epithelium in TNF-R1-deficient mice. Thus,
      TCRgammadelta(+) IEL, when treated with anti-CD3 or anti-TCRgammadelta mAbs,
      induced rapid DNA fragmentation and subsequent detachment of the duodenal and
      jejunal epithelia, but not in the ileum ("the silent ileum"), partly because of
      the paucity of TCRgammadelta(+) IELs in the ileum.

PMID- 14579145
TI  - Perturbations in brain monoamine systems during stress.
AB  - Monoamines modulate the activity of many neurons and there is evidence that a
      balanced synthesis of central nervous monoamines is a prerequisite for normal
      brain functioning. Stress accelerates both release and turnover of brain
      monoamines and the resulting fluctuations in concentrations affect various
      parameters within neurotransmitter systems. Acute stress leads to only transient
      alterations in monoamine systems so that homeostasis can be restored, in
      contrast, chronic stress accompanied by repetitive and/or prolonged stimulation
      of monoaminergic neurons can induce a long-lasting imbalance in central nervous
      neurotransmitter systems. Accordingly, stress-induced changes in brain monoamine
      systems are suspected to contribute to psychiatric diseases such as depression.
      The present paper gives a short overview of stress effects on brain monoamines
      and their receptors.

PMID- 14579146
TI  - Molecular and evolutionary analysis of the growth-controlling region on the human
      Y chromosome.
AB  - The human Y chromosome has been predicted to harbour a locus termed GCY,
      affecting height in males. GCY has been positioned by deletion mapping to the
      pericentromeric region on the long arm of the Y chromosome. As the relevant gene
      has not been identified yet, we have carried out exon amplification and isolated
      nine different exon trap clones within the critical region. Gene prediction
      programs have proposed 17 different gene models and standard BLASTN searches with
      the genomic sequence detected significant homologies to six known
      genes/pseudogenes or expressed sequence tags. Large-scale cDNA library screening
      and reverse transcription of polyA(+) RNAs, however, could not demonstrate
      unequivocally the existence of a novel transcriptional unit. All potential
      transcriptional units are embedded in subintervals of the GCY critical region
      that have been transposed to the human Y during different stages of primate
      evolution. These results challenge our present view on the Y-chromosomal stature
      locus GCY, proposing the existence of an unusual gene with an extremely confined
      spatial and/or temporal expression pattern, albeit the structural impact of the
      nearby pericentromeric heterochromatin should not be excluded.

PMID- 14579147
TI  - Translocation breakpoint mapping and sequence analysis in three monosomy 1p36
      subjects with der(1)t(1;1)(p36;q44) suggest mechanisms for telomere capture in
      stabilizing de novo terminal rearrangements.
AB  - Monosomy 1p36 results from a variety of chromosome rearrangements, including
      terminal deletions, interstitial deletions, derivative chromosomes, and complex
      rearrangements. Our previous molecular studies on a large cohort of monosomy 1p36
      subjects suggest that a significant percentage of terminal deletions of 1p36 are
      stabilized by the acquisition of telomeric sequences from other chromosome ends,
      forming derivative chromosomes (i.e., "telomere capture"). However, the molecular
      mechanism(s) that results in and/or stabilizes terminal deletions of 1p36 by
      telomere capture is poorly understood. In this report, we have mapped the
      translocation breakpoints in three subjects with der(1)t(1;1)(p36;q44)
      chromosomes by fluorescence in situ hybridization (FISH). These results indicate
      that the breakpoint locations are variable in all three subjects, with no common
      1p deletion or 1q translocation breakpoints. In addition, sequence analysis of
      the 1p and 1q breakpoint-containing clones did not identify homologous sequences
      or low-copy repeats in the breakpoint regions, suggesting that nonallelic
      homologous recombination did not play a role in mediating these rearrangements.
      Microsatellite marker analysis indicates that two of the three derivative
      chromosomes were formed by intra-chromosomal rearrangements. These data are
      consistent with a number of recent reports in other model organisms that suggest
      break-induced replication at the site of a double-strand break may act as a
      mechanism of telomere capture by generating nonreciprocal translocations from
      terminally deleted chromosomes. Alternative models are also discussed.

PMID- 14579148
TI  - Inherited variants in MYH are unlikely to contribute to the risk of lung
      carcinoma.
AB  - The base excision repair gene MYH protects against damage to DNA from reactive
      oxygen species, which are commonly found in cigarette smoke. Inherited mutations
      in MYH predispose to colorectal adenomas and carcinomas that show a
      characteristic pattern of somatic G:C-->T:A mutations in the APC gene. A similar
      pattern of somatic mutations in the TP53 gene is reported in smoking-related lung
      cancers. We therefore tested whether germline changes in MYH may also contribute
      to the development of lung cancer by screening for variants in 276 patients with
      lung carcinoma and 106 normal controls. No patients harboured truncating
      mutations in MYH and only a single patient was a carrier for the G382D missense
      mutation. We identified three common coding region (V22M, Q324H and S501F) and
      intronic (157+30A>G, 462+35G>A and 1435-40G>C) variants, but none were over
      represented in the patient samples, indicating that MYH variants are unlikely to
      predispose significantly to the risk of lung cancer.

PMID- 14579151
TI  - On the applicability of a haplotype map to un-assayed populations.
AB  - The rationale for mapping all common haplotypes in our species relies on reports
      of the conservation of haplotype blocks across human populations. Recent findings
      indicate that these blocks may, at least in part, be a random artifact of genetic
      drift. This raises the concern that the latter process may challenge the general
      applicability of a human haplotype map to case-by-case population-specific
      association studies. We develop arguments indicating that even stochastic drift
      originated blocks will, under many conditions, be shared across populations,
      supporting the utilization of a panhuman haplotype map.

PMID- 14579150
TI  - A comparison of the mutation spectra of Menkes disease and Wilson disease.
AB  - The genes for two copper-transporting ATPases, ATP7A and ATP7B, are defective in
      the heritable disorders of copper imbalance, Menkes disease (MNK) and Wilson
      disease (WND), respectively. A comparison of the two proteins shows extensive
      conservation in the signature domains, with amino acid identities outside of the
      conserved domains being limited. The mutation spectra of MNK and WND were
      compared to confirm and refine further regions critical for normal function.
      Mutations were found to be relatively widespread; however, the majority was
      concentrated within defined functional domains and membrane-spanning segments,
      reinforcing the importance of these regions for protein function. Of the total
      published point mutations in ATP7A, 23.0% are splice-site, 20.7% nonsense, 17.2%
      missense, and 39.1% small insertions/deletions. There is a high prevalence
      (58.2%) of missense mutations in ATP7B. For the other mutations in ATP7B, 7.4%
      are splice-site, 7.4% nonsense, and 27.0% small insertions/deletions. A region of
      possible importance is the intervening sequence between the last copper-binding
      domain and the first transmembrane helix, as this region has a high percentage of
      MNK mutations. Similarly, the region containing the ATP-binding domain has 24.6%
      of all WND mutations. The study of mutation locations is useful for defining
      critical regions or residues and for efficient molecular diagnosis.

PMID- 14579153
TI  - Coxsackieviral replication and pathogenicity: lessons from gene modified animal
      models.
AB  - Coxsackieviruses have been implicated in the pathogenesis of human myocarditis
      and some forms of dilated cardiomyopathy. A considerable portion of our knowledge
      about the pathophysiology of viral heart disease is derived from animal studies.
      In particular, investigations utilising gene-targeted mice provide valuable new
      insights into various aspects of viral pathogenicity and host factors involved in
      the control of viral replication. This review focuses on models in cell culture
      and transgenic animals mimicking coxsackieviral persistence, demonstrating that
      remarkably low persisting levels of replication-restricted coxsackieviral genomes
      are associated with an induction of a cytopathic effect in cardiac myocytes,
      leading to dilated cardiomyopathy in a transgenic mouse model. In this particular
      animal model, a phenotype is revealed which closely resembles the major hallmarks
      of human dilated cardiomyopathy. The impact of the innate immune system on
      coxsackieviral replication is demonstrated by studies in gene-targeted mice
      deficient of either type I or type II interferon signalling, which have indicated
      that type I but not type II interferons are essential for the control of early
      viral replication and survival of coxsackieviral infection.

PMID- 14579154
TI  - Developmental changes at the materno-embryonic interface in early pregnancy of
      the alpaca, Lamos pacos.
AB  - This study analyses the manner in which trophoblast cells adhere to uterine
      epithelium and the subsequent interactions that contribute to the establishment
      of epitheliochorial placentation in the alpaca Lama pacos. Specimens at the
      luteal and follicular phases and at 22, 26, 30 and 45 days of pregnancy (op) were
      processed for morphological studies. On day 15 op, the blastocysts are completely
      free within the uterine lumen, with implantation starting around day 20. On days
      22 and 26 of gestation, the trophoblast is apposed to the epithelial surface of
      the uterus, with areas of contact and adhesion by means of complex
      interdigitation. Implantation sites occur prevalently in the left uterine horn,
      but an expanded trophoblast also occupies large extensions of the right horn,
      where the maternofetal interaction shows peculiar areas of apposition. As
      development continues, attachment areas become more extensive. On days 30 and 45,
      many secretory granules can be seen in the uterine epithelium, while giant
      multinucleate cells appear interposed between the remaining trophoblast cells,
      showing intense alkaline phosphatase activity, deposits containing iron and PAS
      positive granules. Placental lactogen hormone is not present within the cytoplasm
      of the binucleate or multinucleate trophoblast cells. By day 30 of gestation, the
      trophoblast layer is lined by an extraembryonic connective tissue that by day 45
      is well vascularized, thus indicating the starting point of placental formation.
      Fetal and maternal capillaries indent the epithelium and the trophoblast,
      narrowing the specialized areas of exchange, which occur along the entire
      maternofetal interface, characterizing the diffuse nature of this placenta.

PMID- 14579152
TI  - Glutaric aciduria type 1 and neonatal screening: time to proceed--with caution.
AB  - The new technology of tandem mass spectrometry is having a significant impact on
      the diagnostics of inborn metabolic errors. One of the most important aspects of
      this new technology is the possibility of recognising a whole class of disorders
      within a single analytical step. Shall this powerful technology be applied to the
      screening of newborn babies? Careful evaluation of every single disorder that
      could potentially be identified is needed. In the following, I will present some
      considerations that concern glutaric aciduria type 1 (MIM 231670; glutaryl-CoA
      dehydrogenase deficiency).

PMID- 14579156
TI  - Abstracts of the 18th International Congress Laser Medicine. November 6-8, 2003,
      Florence, Italy.

PMID- 14579157
TI  - Report on the African league against rheumatism (1999-2003).

PMID- 14579155
TI  - A single recessive mutation in the proteolytic machinery of Arabidopsis
      chloroplasts impairs photoprotection and photosynthesis upon cold stress.
AB  - Intracellular proteases, together with molecular chaperones, are components of
      the cellular protein quality control system. Although the identity of chloroplast
      proteases has been revealed in recent years, little is known about their
      regulation. As a first step towards identifying unknown functional or regulatory
      components of the chloroplast proteolytic machinery, a genetic screen was devised
      with the aim of generating Arabidopsis thaliana (L.) Heynh. mutants impaired in
      chloroplast protein degradation. A streptomycin-resistance gene was fused to a
      cDNA construct that encodes an unstable mutant of the OE33 protein. This chimeric
      gene was used for transforming Arabidopsis plants. Analysis of transgenic plants
      revealed a correlation between streptomycin resistance and accumulation of the
      recombinant fusion protein. Seeds from transgenic plants that were sensitive to
      streptomycin were chemically mutagenized and screened for resistance to
      streptomycin. Such resistance could be due to stabilization of the protein caused
      by a mutation in the chloroplast proteolytic machinery. Genetic analysis of one
      of the mutants showed the mutation to be recessive, in a single nuclear gene.
      Further characterization of the mutant revealed that it was not a result of
      increased transcription of the transgene. Moreover, chloroplast lysates from the
      mutant plant showed decreased ATP-dependent degradation of a chloroplast protein
      substrate, consistent with the conclusion that the mutation impaired the
      proteolytic machinery. Physiological analysis revealed that upon cold stress,
      photoprotection and photosynthesis in the mutant was inhibited, suggesting that
      the chloroplast proteolytic machinery is involved in repairing damage incurred to
      the photosynthetic machinery upon exposure to cold temperatures.

PMID- 14579158
TI  - The efficacy of oral cyclophosphamide plus prednisolone in early diffuse systemic
      sclerosis.
AB  - Pharmacological treatment of diffuse systemic sclerosis (SSc) directed at the
      tissue fibrosis has generally been ineffective. Many immunosuppressive drugs have
      been tried as therapy for SSc, regardless of the disease subtype and/or stage.
      The aim of this study was to show the efficacy and the toxicity of oral
      cyclophosphamide and prednisolone therapy on the prevention of fibrosis-based
      tissue damage in the early stages of the diffuse SSc. Twenty-seven patients with
      early diffuse SSc were treated with oral cyclophosphamide (1-2 mg/kg/day) plus
      oral prednisolone (40 mg/every other day) between the years 1995 and 1998. The
      results regarding the efficacy and toxicity of cyclophosphamide were compared
      with those of 22 early SSc patients who had been treated with oral D
      penicillamine between 1992 and 1995. All the patients were evaluated using
      clinical and laboratory parameters every 6 months for 2 years. There was a
      significant improvement on the skin score, maximal oral opening, flexion index,
      predicted forced vital capacity (FVC) and carbon monoxide diffusing capacity
      (DLCO) in the cyclophosphamide group. The decrease in skin score in the
      cyclophosphamide group started earlier than in the D-penicillamine group. No life
      threatening or irreversible adverse reaction was observed. This open study
      supports the use of oral cyclophosphamide plus prednisolone therapy to prevent
      fibrosis and its complications in the early stages of diffuse SSc.

PMID- 14579159
TI  - Gout in systemic lupus erythematosus and overlap syndrome - a hospital-based
      study.
AB  - The negative association between gout and rheumatoid arthritis is widely
      accepted, and gout is also speculated to be rare in systemic lupus erythematosus
      (SLE), as only a few sporadic cases have been reported. From 1985 to 2001 we
      encountered 15 lupus patients at Chang-Gung Memorial Hospital, including two with
      lupus-scleroderma and one with lupus-scleroderma-polymyositis overlap syndrome
      coexisting with gout. This study retrospectively analyses the clinical and
      laboratory characteristics of these patients. A lower female predominance is
      found, and most patients developed gout after the onset of SLE, although gout
      preceded SLE in two cases. Measurement of serum uric acid and 24-h urine uric
      acid found all of the patients to be hyperuricaemic and underexcretors of uric
      acid. Furthermore, most of the patients (14/15) were receiving diuretics. Also,
      many had hypertension and serious cardiovascular diseases. Renal impairment
      during gouty attacks seemed to be a predisposing factor for developing end-stage
      renal disease. Gouty arthritis usually occurred during relative SLE inactivity,
      podagra was frequent, and tophi were found in a few patients. Compared with the
      unselected population of SLE patients, the cases studied here had a higher
      incidence of chronic arthritis, malar rash, haematologic disorder,
      photosensitivity, serositis and neurologic disorder. Renal disease in the
      patients sampled was frequently membranous nephropathy.

PMID- 14579160
TI  - Efficacy of transforaminal versus interspinous corticosteroid injectionin discal
      radiculalgia - a prospective, randomised, double-blind study.
AB  - A prospective, randomised, double-blind study was carried out to compare the
      respective efficacies of transforaminal and interspinous epidural corticosteroid
      injections in discal radiculalgia. Thirty-one patients (18 females, 13 males)
      with discal radicular pain of less than 3 months' duration were consecutively
      randomised to receive either radio-guided transforaminal or blindly performed
      interspinous epidural corticosteroid injections. Post-treatment outcome was
      evaluated clinically at 6 and 30 days, and then at 6 months, but only by mailed
      questionnaire. At day 6, the between-group difference was significantly in favour
      of the transforaminal group with respect to Schober's index, finger-to-floor
      distance, daily activities, and work and leisure activities on the Dallas pain
      scale. At day 30, pain relief was significantly better in the transforaminal
      group. At month 6, answers to the mailed questionnaire still showed significantly
      better results for transforaminal injection concerning pain, daily activities,
      work and leisure activities and anxiety and depression, with a decline in the
      Roland-Morris score. In recent discal radiculalgia, the efficacy of radio-guided
      transforaminal epidural corticosteroid injections was higher than that obtained
      with blindly-performed interspinous injections.

PMID- 14579162
TI  - Subclinical pulmonary haemorrhage causing a restrictive lung defect in three
      siblings with a unique urticarial vasculitis syndrome.
AB  - Three siblings with urticarial vasculitis syndrome (UVS) are described. All had
      restrictive lung function abnormalities caused by subclinical pulmonary
      haemorrhage. The latter was suspected after finding haemosiderin-laden
      macrophages and a friable bronchial mucosa during elective bronchopulmonary
      alveolar lavage (BAL). The chest radiographs were normal at presentation but
      after steroid withdrawal symptoms worsened, haemoglobin levels fell, and Case 1
      developed acute pulmonary haemorrhage. This was documented by lung biopsy, which
      also revealed evidence of old haemorrhage and fibrosis. We concluded that these
      patients had a unique familial variant of UVS with a previously unreported
      restrictive lung disease due to subclinical pulmonary haemorrhage.

PMID- 14579161
TI  - Expression of NKB1 on peripheral T cells in patients with rheumatoid arthritis.
AB  - NKB1 inhibits cytoxic activity of T lymphocytes mediated by superantigens, which
      is one of the contributing factors in the pathogenesis of rheumatoid arthritis
      (RA). In this study, we determined the expression of NKB1 on peripheral blood T
      cells in patients with RA. Our findings revealed that among patients with RA,
      NKB1(+) CD8(+ )T cells decreased significantly in comparison to controls (ratio:
      P < 0.05; absolute number: P < 0.005), and this decrease was not related to or
      influenced by HLA-Bw4 as a ligand of NKB1. This result may suggest that decreased
      expression of NKB1(+) CD8(+ )T cells contributes to the pathogenesis of RA
      mediated by the activation of CD8(+) T cells.

PMID- 14579163
TI  - Colchicine treatment in children with familial Mediterranean fever.
AB  - Prophylactic colchicine therapy has been shown to be a safe and effective method
      of eliminating the attacks and preventing the development of amyloidosis in
      patients with familial Mediterranean fever (FMF). However, information about
      effective dosages that control FMF attacks and prevent amyloidosis in childhood
      is not available. The aim of this study is to determine the 'effective colchicine
      dose' for children in terms of body weight and surface area. Sixty-two (34 male,
      28 female) children with FMF were selected and colchicine treatment was initiated
      by giving 0.5-1 mg/day to each patient. The dose was gradually increased up to a
      maximum 2 mg/day in unresponsive patients; mean duration of therapy was 45.6 +/-
      35.5 months. When the 'optimal effective dosage' (i.e. the one that reduced the
      frequency of attacks and ESR, CRP and fibrinogen levels during the attack-free
      period) was achieved, the optimal effective dose was calculated according to the
      body weight and body surface area for each patient. Based on these values 'mean
      colchicine dose' was computed for the study group and values for different age
      groups were evaluated. Mean colchicine doses according to the body weight and
      surface area of the whole group were found to be 0.03 +/- 0.02 mg/kg/day and 1.16
      +/- 0.45 mg/m(2)/day, respectively. It was shown that children less than 5 years
      of age might need colchicine doses as high as 0.07 mg/kg/day or 1.9 mg/m(2)/day.
      These dosages are approximately 2.5-3 times more than the 'mean colchicine dose'
      for children aged 16-20 years. These results clearly show that small children
      need higher doses of colchicine in order to control their attacks. Thus, we
      conclude that colchicine, when given according to body weight or body surface
      area, would be more effective in childhood.

PMID- 14579164
TI  - Bone mineral density changes in women with systemic lupus erythematosus.
AB  - The aim of this study was to analyse the heterogeneity of bone mineral density
      (BMD) reduction across measurement sites in female systemic lupus erythematosus
      (SLE) patients on glucocorticoid (CS) treatment. The study population consisted
      of two subgroups: 32 women at a mean (SD) age of 43.2 (12.0) years, SLE duration
      of 13.4 (6.2) years, treated with a mean cumulative prednisone dose of 34.4 g;
      and 16 women at a mean age of 36.1 (9.0) years, SLE duration of 3.2 (2.0) years,
      never treated with glucocorticoids (control group). The participants underwent a
      standardised interview, medical record review, blood sampling and BMD examination
      of the lumbar spine, femoral neck and distal forearm by dual-energy X-ray
      absorptiometry. CS-treated participants were supplemented with daily calcium
      (1200 mg) and vitamin D (500 UI). During the study mean daily glucocorticoid dose
      was 10 mg prednisone equivalent. The controls did not receive either
      corticosteroids or calcium and vitamin D. BMD and laboratory parameters were re
      examined at the end of the second year. At baseline 22 (68.7%) of the CS-treated
      participants had osteoporosis at least at one major site, compared to 18.8% of
      the controls. The BMD reduction was proportional to the trabecular bone content
      at the specific measurement site. At baseline mean T scores in the CS-treated
      group were the highest at the forearm (-1.03 +/- 1.13), followed by the hip (
      1.32 +/- 1.26), AP spine (-1.87 +/- 1.46) and lateral spine (-2.90 +/- 1.50). At
      follow-up lateral spine bone loss was 5.54% per year, the total hip and the
      forearm lost 3.59% and 0.33%, respectively, compared to annual losses of 1.02%
      (AP spine), 1.30% (lateral spine), 0.83% (total hip) and 0.11% (forearm) in the
      control group. The heterogeneity of BMD reduction in our SLE population
      emphasises the need for the targeted use of bone densitometry in steroid-treated
      patients. Attention should be paid to trabecular-rich sites, and fracture risk
      should be specifically determined.

PMID- 14579165
TI  - Interstitial granulomatous dermatitis with plaques and arthritis.
AB  - Interstitial granulomatous dermatitis and arthritis (IGDA) is a rare disease
      entity with female predominance. The case of a 53-year-old woman with erythemas,
      plaques and nodules associated with polyarthritis is presented. She was treated
      with cyclosporin A, with improvement of the joint affliction and complete
      clearance of skin lesions. The differential diagnosis of IGDA is discussed
      briefly.

PMID- 14579166
TI  - Post-streptococcal reactive arthritis and glomerulonephritis in an adult.
AB  - We report the case of an adult who developed severe post-streptococcal reactive
      arthritis (PSRA) and poststreptococcal glomerulonephritis (PSGN) after a
      subclinical streptococcal infection. Antistreptococcal antibody titres, renal
      biopsy and the clinical course confirmed the diagnosis. Coincidence of PSRA and
      PSGN is rare in the adult population and the potential for misdiagnosis exists,
      particularly when prior streptococcal infection is not apparent. The clinical
      manifestations of poststreptococcal syndromes are highly variable, and the
      diagnosis of concomitant PSRA and PSGN should be considered when patients present
      with glomerulonephritis and inflammatory arthritis. Factors from both the host
      and the pathogen are probably important in determining disease expression in
      poststreptococcal syndromes.

PMID- 14579167
TI  - Rheumatoid-like polyarthritis as a presenting feature of metastatic carcinoma: a
      case presentation and review of the literature.
AB  - The case of a 69-year-old woman who presented with abrupt onset of rheumatoid
      like symmetrical polyarthritis but who was subsequently diagnosed to have
      disseminated abdominal carcinomatosis is reported. The temporal relationship
      between the joint symptoms and the discovery of carcinoma suggested that the
      arthritis was a paraneoplastic manifestation of the latter. An underlying
      malignancy should always be looked for in elderly patients who present with
      explosive polyarthritis for the first time, particular if unexplained anaemia or
      constitutional symptoms persist after treatment.

PMID- 14579168
TI  - Systemic lupus erythematosus and thrombotic thrombocytopenic purpura: a case
      report and literature review.
AB  - We describe a patient with systemic lupus erythematosus (SLE) who developed
      severe and acute thrombotic thrombocytopenic purpura (TTP). Detection of the
      fragmentation of peripheral red blood cells (RBC) helped the early diagnosis of
      TTP and the patient was rescued by extensive plasma exchange started promptly
      after the diagnosis. Because manifestations of TTP are similar to those in SLE,
      it is sometimes difficult to make an accurate diagnosis of TTP in SLE patients.
      We emphasise here the significance of the early diagnosis of TTP by the
      observation of fragmented RBC and the intensive therapy, including plasma
      exchange, for this very severe condition.

PMID- 14579170
TI  - Infliximab in a case of early adult-onset Still's disease.

PMID- 14579169
TI  - Bilateral Achilles tendinitis with spontaneous rupture induced by levofloxacin in
      a patient with systemic sclerosis.

PMID- 14579172
TI  - Intracellular distribution of cowpea mosaic virus movement protein as visualised
      by green fluorescent protein fusions.
AB  - Cowpea mosaic virus (CPMV) derivatives expressing movement protein (MP) green
      fluorescent protein (GFP) fusions (MP:GFP) were used to study the intracellular
      targeting and localization of the MP in cowpea protoplasts and plants. In
      protoplasts, a virus coding for a wild type MP:GFP (MPfGFP) induced the formation
      of fluorescent tubular structures, which shows that subcellular targeting and
      tubule formation are not affected by fusion of GFP to the C-terminus of the MP.
      In plants, MPfGFP infections were mostly confined to single epidermal cells and
      failed to achieve a systemic infection, probably because the fusion of GFP to the
      MP interfered with MP-virion interaction. MP:GFP mainly accumulated in
      fluorescent spots in the cell wall of epidermal cells of inoculated leaves, which
      may represent short tubular structures in modified plasmodesmata. At the cuticle
      side of epidermal cells tubular structures were detected indicating that tubule
      formation in plants, as in protoplasts, does not require the presence of
      functional plasmodesmata. Furthermore, results were obtained which indicate that
      CPMV MP:GFP is able to traffic from cell-to-cell by itself. The possible
      significance of this finding is discussed.

PMID- 14579171
TI  - Expression at mRNA level of cytokines and A238L gene in porcine blood-derived
      macrophages infected in vitro with African swine fever virus (ASFV) isolates of
      different virulence.
AB  - Porcine macrophage cultures were infected with two ASFV isolates of variable
      virulence and mRNA levels of several relevant macrophage-derived cytokines were
      quantified by real time PCR. At six hours post infection, a clear enhancement of
      mRNA expression of TNFalpha, IL6, IL12 and IL15 was observed in macrophages
      infected with the low virulent ASFV/NH/P68 (NHV) when compared to those infected
      with the highly virulent ASFV/L60 (L60). The sequence of the A238L gene homologue
      to the cellular IkappaB was found identical in both viral isolates and its
      expression at mRNA level was higher in macrophages infected with NHV when
      compared to macrophages infected with L60. Furthermore our results suggest a
      negative correlation between the mRNA expression of A238L gene and the mRNA
      expression of the above mentioned cytokines (with the exception of IL10) in L60
      infected macrophages in opposition to the positive correlation (with exception of
      the IL1) suggested in NHV infection. Overall, our data strongly emphasize that
      virulence of ASFV isolates may depend on their capacity to regulate the
      expression of macrophage-derived cytokines relevant for the development of host
      protective responses by yet unknown mechanisms triggered by the virus at early
      stages of the cellular infection.

PMID- 14579173
TI  - Biological and molecular characterization of P101 isolate, a tobamoviral pepper
      strain from Bulgaria.
AB  - A tobamovirus isolated from pepper crops in Bulgaria has been characterized, and
      is referred to below as P101. It was closely related to Paprika mild mottle virus
      (PaMMV) (Dutch isolate), based upon the serological relationship of its coat
      protein, and the nucleotide sequence analysis of the gene encoding the coat
      protein and the 3' non-coding region of the viral RNA. The coat proteins of the
      two isolates differ by two amino acids, and these substitutions may be
      responsible for the different reactivity of the isolates towards a polyclonal
      antiserum raised against the virion of the Dutch isolate. The biological
      behaviour of both isolates was similar in the hosts tested, except in pepper
      plants where P101 induced delayed and milder symptoms compared with PaMMV,
      although their accumulation levels were similar. In addition, we investigated the
      infection pattern of the two isolates in tomato plants. Both isolates accumulated
      in protoplasts as well as in inoculated leaves, although systemic invasion was
      limited. This limited spread was not due to activation of defense mechanism(s) in
      the plant, since the upper uninoculated leaves from P101-infected tomato plants
      were fully susceptible to challenge inoculation with the virus. Instead, it
      appears due to a restriction of long-distance movement, that could be overcome in
      tomato plants co-infected with Tobacco mosaic virus (TMV), but not with either
      Cucumber mosaic virus or Pepino mosaic virus. The ability of P101 to move
      systemically in the presence of TMV was not linked to enhanced accumulation of
      P101 at the cellular level. Thus, a tobamovirus but not the viruses tested from
      other genera could complement, in trans, the function(s) required for PaMMV to
      invade the upper uninoculated leaves. Paprika mild mottle virus strain B is
      proposed as the name for this new isolate.

PMID- 14579174
TI  - The complete nucleotide sequence of Plum pox virus isolates from sweet (PPV-SwC)
      and sour (PPV-SoC) cherry and their taxonomic relationships within the species.
AB  - Plum pox virus (PPV) sweet (SwC) and sour (SoC) cherry isolates were the first
      PPV isolates to be recovered from natural infection in sweet and sour cherry
      plants, respectively. Their complete nucleotide sequences have been determined
      finding a deduced genome organisation typical for PPV species. Both genomes are
      9795 nucleotides long, excluding the 3' terminal poly(A) tail, and contain an
      open reading frame of 9432 nt, encoding a polyprotein of 3143 amino acids. The
      nucleotide and predicted amino acid sequences of PPV-SwC and SoC have been
      pairwise compared with available sequences of different PPV strains. Although a
      very high similarity exists between the whole genomes and polyproteins of the two
      cherry isolates, high levels of divergence have been calculated with sequences of
      PPV-M, D and EA isolates. In particular, the most considerable divergence has
      been found in part of 5' non coding region, in regions encoding P1, P3 + 6K1, 6K2
      and NIa-VPg proteins as well as in the N-terminal domain of the coat protein.
      Phylogenetic analysis have been undertaken in order to establish the taxonomic
      localisation of SwC and SoC isolates within PPV species, showing that they are
      always clustered together and separated from the rest of PPV strains, being
      clearly the most distant.

PMID- 14579175
TI  - Variability of the coat protein gene of Citrus psorosis virus in Campania,
      southern Italy.
AB  - Variability of the Coat protein (CP) gene of Citrus psorosis virus (CPsV) was
      assessed serologically, and by sequence analyses of two genomic regions located
      in the 3' (region C) and 5' (region V) halves of the gene. Analysis of 53
      psorosis field sources from Campania, Italy, with 23 monoclonal antibodies
      revealed nine serogroups and at least ten different epitopes. Sequence analysis
      of 19 of these sources showed limited nucleotide diversity of the CP gene in the
      population. Diversity was slightly higher in region V than in region C.
      Phylogenetic analysis of the V and C regions of the CP showed that the Campania
      sources of CPsV were clearly separated from the CPsV-4 isolate from Florida. For
      C region, most of the CPsV sources clustered together, whereas two clusters were
      observed for region V. The ratio between nonsynonymous and synonymous
      substitutions for regions C (0.083) and V (0.345) indicated negative selective
      pressure for amino acid changes, more intense in the C region. No correlation was
      found between serogroups and specific aminoacid sequences, field location or
      citrus cultivar.

PMID- 14579176
TI  - Rice stripe virus 23.9 K protein aggregates and forms inclusion bodies in
      cultured insect cells and virus-infected plant cells.
AB  - The genome of Rice stripe virus (RSV, genus Tenuivirus) contains seven open
      reading frames (ORFs). Little is known about the products of four of these ORFs,
      including the 23.9 K protein encoded by the virus-sense ORF of RNA3. Western
      blotting revealed that the 23.9 K protein was synthesized in the host plant and
      also in the planthopper vector of RSV. Using a baculovirus vector, the 23.9 K
      protein was expressed, both unfused and fused with red-shifted green fluorescent
      protein, in Spodoptera frugiperda cells. Inclusion bodies were observed by light
      microscope in cells expressing fused or unfused proteins. Inclusion bodies in
      cells expressing the fused protein fluoresced under blue light. By immunoelectron
      microscopy, electron-dense inclusion bodies in cells expressing the unfused
      protein were specifically labeled with 23.9 K protein antiserum. Moreover,
      electron-dense masses labeled with 23.9 K protein antiserum were observed in
      virus-infected wheat tissue by electron microscopy. This paper thus demonstrates
      that RSV 23.9 K protein can aggregate in vivo and form inclusion bodies in
      infected plant tissue.

PMID- 14579177
TI  - Cladistic analysis of iridoviruses based on protein and DNA sequences.
AB  - Cladograms of iridoviruses were inferred from bootstrap analysis of molecular
      data sets comprising all published protein and DNA sequences of the major capsid
      protein, ATPase and DNA polymerase genes of members of the Iridoviridae family
      Iridovirus. All data sets yielded cladograms supporting the separation of the
      Iridovirus, Ranavirus and Lymphocystivirus genera, and the cladogram based on
      data derived from major capsid proteins further divided both the Iridovirus and
      Ranavirus genera into two groups. Tests of alternative hypotheses of topological
      constraints were also performed to further investigate relationships between
      infectious spleen and kidney necrosis virus (ISKNV), an unclassified fish
      iridovirus for which the complete genome sequence data is available, and other
      iridoviruses. Cladograms inferred and results of Shimodaira-Hasegawa tests
      indicated that ISKNV is more closely related to the Ranavirus genus than it is to
      the other genera of the family.

PMID- 14579178
TI  - Immunodominant domains of the Measles virus hemagglutinin protein eliciting a
      neutralizing human B cell response.
AB  - The most important neutralizing and protective antibodies against Measles virus
      (MeV) are directed against the hemagglutinin protein (MeV-H). To define the MeV
      binding domains recognized by human antibodies a set of 10 non-redundant MeV-H
      specific monoclonal antibodies (mabs) was used to block their binding in a
      competition ELISA. Sera from both naturally infected and vaccinated individuals
      showed similar competition patterns. Two distinct domains were identified as the
      main target of human antibodies. One domain corresponded to the region of the
      previously described hemagglutinin noose epitope (HNE, aa 380-400) [35], which is
      recognized by hemagglutination-inhibiting, neutralizing and protective mabs. The
      second region is defined by a mab with strong neutralizing but weak
      hemagglutination-inhibiting activity. Mabs with a strong neutralizing capacity
      with respect to wild-type viruses seemed to displace more human antibodies than
      those with a weaker neutralizing activity. Human antibodies seem to react more
      weakly with the hemagglutinin regions that bind the CD46 and the fusion protein
      and more strongly with the putative CD150 binding site and the top loops of beta
      sheet 2 and 3 of the hemagglutinin.

PMID- 14579179
TI  - A comparative sequence analysis to revise the current taxonomy of the family
      Coronaviridae.
AB  - The Coronaviridae family, comprising the Coronavirus and Torovirus genera, is
      part of the Nidovirales order that also includes two other families,
      Arteriviridae and Roniviridae. Based on genetic and serological relationships,
      groups 1, 2 and 3 were previously recognized in the Coronavirus genus. In this
      report we present results of comparative sequence analysis of the spike (S),
      envelope (E), membrane (M), and nucleoprotein (N) structural proteins, and the
      two most conserved replicase domains, putative RNA-dependent RNA polymerase
      (RdRp) and RNA helicase (HEL), aimed at a revision of the Coronaviridae taxonomy.
      The results of pairwise comparisons involving structural and replicase proteins
      of the Coronavirus genus were consistent and produced percentages of sequence
      identities that were distributed in discontinuous clusters. Inter-group pairwise
      scores formed a single cluster in the lowest percentile. No homologs of the N and
      E proteins have been found outside coronaviruses, and the only (very) distant
      homologs of S and M proteins were identified in toroviruses. Intragroup sequence
      conservation was higher, although for some pairs, especially those from the most
      diverse group 1, scores were close or even overlapped with those from the
      intergroup comparisons. Phylogenetic analysis of six proteins using a neighbor
      joining algorithm confirmed three coronavirus groups. Comparative sequence
      analysis of RdRp and HEL domains were extended to include arterivirus and
      ronivirus homologs. The pairwise scores between sequences of the genera
      Coronavirus and Torovirus (22-25% and 21-25%) were found to be very close to or
      overlapped with the value ranges (12 to 22% and 17 to 25%) obtained for
      interfamily pairwise comparisons, but were much smaller than values derived from
      pairwise comparisons within the Coronavirus genus (63-71% and 59-67%).
      Phylogenetic analysis confirmed toroviruses and coronaviruses to be separated by
      a large distance that is comparable to those between established nidovirus
      families. Based on comparison of these scores with those derived from analysis of
      separate ranks of several multi-genera virus families, like the Picornaviridae, a
      revision of the Coronaviridae taxonomy is proposed. We suggest the Coronavirus
      and Torovirus genera to be re-defined as two subfamilies within the Coronavirdae
      or two families within Nidovirales, and the current three informal coronavirus
      groups to be converted into three genera within the Coronaviridae.

PMID- 14579180
TI  - The complete nucleotide sequence of Subterranean clover mottle virus.
AB  - The complete nucleotide sequence of Subterranean clover mottle virus (SCMoV)
      genomic RNA has been determined. The SCMoV genome is 4,258 nucleotides in length.
      It shares most nucleotide and amino acid sequence identity with the genome of
      Lucerne transient streak virus (LTSV). SCMoV RNA encodes four overlapping open
      reading frames and has a genome organisation similar to that of Cocksfoot mottle
      virus (CfMV). ORF1 and ORF4 are predicted to encode single proteins. ORF2 is
      predicted to encode two proteins that are derived from a -1 translational
      frameshift between two overlapping reading frames (ORF2a and ORF2b). A search of
      amino acid databases did not find a significant match for ORF1 and the function
      of this protein remains unclear. ORF2a contains a motif typical of chymotrypsin
      like serine proteases and ORF2b has motifs characteristically present in positive
      stranded RNA-dependent RNA polymerases. ORF4 is likely to be expressed from a
      subgenomic RNA and encodes the viral coat protein. The ORF2a/ORF2b overlapping
      gene expression strategy used by SCMoV and CfMV is similar to that of the
      poleroviruses and differ from that of other published sobemoviruses. These
      results suggest that the sobemoviruses could now be divided into two distinct
      subgroups based on those that express the RNA-dependent RNA polymerase from a
      single, in-frame polyprotein, and those that express it via a -1 translational
      frameshifting mechanism.

PMID- 14579181
TI  - Characterization of a new potyvirus isolated from Chinese artichoke in Japan.
AB  - Afilamentous virus was isolated in Japan from virus-infected Chinese artichoke
      showing mosaic symptoms. This virus was assigned to the genus Potyvirus, based on
      particle morphology and serological properties. The virus could be transmitted to
      several test plants but not to Perilla frutesence, the host plant of Perilla
      mottle virus. cDNA corresponding to the 3'-terminal 1675 nucleotides of the viral
      RNA, excluding the poly (A) tail, was cloned and sequenced. The amino acid
      sequence of the coat protein was different from those of 74 distinct potyviruses.
      Therefore, we propose that the new potyvirus should be designated as Chinese
      artichoke mosaic virus (ChAMV).

PMID- 14579182
TI  - Endogenous retrovirus HC2 pol fragments in the squirrel monkey: expression,
      evolution, and phylogeny.
AB  - Human endogenous retrovirus HC2 is an incomplete provirus containing the entire
      gag and pol genes and a 3' LTR, whereas the 5' LTR and env gene are missing. We
      investigated expression of the HC2 pol gene in the squirrel monkey ( Saimiri
      sciureus) by RT-PCR. The pol gene was expressed in cerebellum, liver, lung, and
      spleen of the squirrel monkey, but not in six other tissues tested. RT-PCR
      products were cloned and sequenced resulting in seven sequences that were
      analyzed. These sequences showed 73.7-89.2% sequence similarity to HC2 pol genes
      present in the human genome. No frameshifts or termination codons caused by
      deletion/insertion or point mutation were found in clones SM-HC27-1 and SM-HC27-4
      isolated from squirrel monkey lung tissues. Phylogenetic analysis showed that HC2
      pol elements from the squirrel monkey were randomly clustered with those in human
      genome and the genomes of other nonhuman primates, indicating that substantial
      evolution of the HC2 elements occurred prior to primate speciation with
      additional evolution of the elements, independent of each other, after
      speciation.

PMID- 14579183
TI  - Carboxy-terminally truncated Dengue 4 virus envelope glycoprotein expressed in
      Pichia pastoris induced neutralizing antibodies and resistance to Dengue 4 virus
      challenge in mice.
AB  - We have expressed a recombinant Dengue 4 virus envelope glycoprotein (E4rec),
      truncated at its C-terminus by 53 amino acids, in Pichia pastoris. The presence
      of E4rec was confirmed by Western-blot using anti-DEN 4 hyper immune mouse
      ascitic fluid. E4rec migrated during SDS-PAGE as a 64 kDa protein. Treatment with
      endoglycosidases showed that the E protein was modified by the addition of short
      mannose chains and the absence of hyperglycosylation. When administered to BALB-C
      mice, E4rec elicited a DEN 4 neutralizing antibody response haemagglutination
      inhibition antibodies and specific memory T cell response. Mice immunized were
      also significantly protected against lethal DEN 4 virus challenge (86.6%, p <
      0.001).

PMID- 14579184
TI  - A minor outer capsid protein, P9, of Rice dwarf virus.
AB  - Partial amino acid sequence of a minor 30 kDa polypeptide in purified Rice dwarf
      virus (RDV) was identical to the deduced amino acid sequence encoded by the dsRNA
      segment S9 of the virus. This polypeptide was specifically detected by Western
      blotting analysis with antibodies raised against the product of S9 expressed in a
      baculovirus system. Treatment of purified RDV particles with a relatively higher
      concentration of MgCl2 removed the polypeptide from core particles together with
      other outer capsid proteins. These results demonstrate that the 30 kDa
      polypeptide is a minor outer capsid protein that is encoded by genome segment S9
      of RDV. This protein was named P9 protein.

PMID- 14579185
TI  - [New Insights into the Etiological Pathogenesis of Peyronie's Disease].
AB  - This paper reviews the current knowledge of the etiological pathogenesis of
      Peyronie's disease. De la Peyronie himself supposed a connection with venereal
      diseases. Herein, infectious, traumatic, autoimmune and genetic causes are
      discussed. An important hypothesis is that the recurrent microtraumatisation of
      the tunica albuginea during sexual intercourse leads to small lesions that
      activate processes of wound healing and development of fibrotic plaque. According
      to recent data, an association with the antigens of the HLA-system could be ruled
      out. Transforming growth factor beta (TGF-beta) seems to have an important impact
      due to its increased expression in the plaque. Furthermore it is possible to
      induce a condition similar to Peyronie's disease by intratunical injection of
      cytomodulin - a substance with TGF-beta-like activity - in an animal model. As in
      other fibrotic diseases, an imbalance between nitric oxide (NO) and reactive
      oxygen species (ROS) seems to be of importance. The most important new insights
      were gained from cell-culture models in which increased expression of basic
      fibroblast growth factor (bFGF), as well as a change in cell cycle regulation
      (p53) and cytogenetic instability were observed.

PMID- 14579186
TI  - [Ranking of pelvic lymphadenectomy in therapy and prognosis of carcinoma of the
      bladder].
AB  - PURPOSE: Due to the absence of internationally recognised guidelines on the
      necessary extent of lymphatic node removal in carcinoma of the bladder, we are
      still not sure as to which procedure is most favourable to therapeutic success.
      Hence, we checked retrospectively on the influence exercised by radical surgery
      on prognosis. MATERIAL AND METHOD: 506 patients were analysed retrospectively
      after radical cystectomy and pelvic lymphadenectomy with regard to the influence
      exercised on prognosis by clinical and histopathological variables. RESULTS:
      Statistically significant influential factors in univariate analysis were in the
      retrospective examination: the pT category (p < 0.0001), lymphatic node status (p
      < 0.0001), grading (p = 0.0145), proof of uronephrosis (p = 0.0007), number of
      performed transurethral resections (p = 0.0043), surgeon (p = 0.0033) and number
      of resected lymph nodes (p = 0.0012). There was a significant difference between
      surgeons at a median number of 14.3 removed lymphatic nodes (range 1 - 46) in
      respect of radicality (p = 0.001) and prognosis (p < 0.0049). Independent
      influential factors in multivariate analysis were: pT category (p = 0.003), pN
      category (p < 0.001) and the number of surgically removed lymphatic nodes (p =
      0.038). CONCLUSION: In our retrospectively examined group of patients extensive
      lymphadenectomy significantly improved the prognosis and was thus a potentially
      curative procedure. Basing on these results, prospective studies will have to
      clarify the level of the standard applicable to pelvic lymphadenectomy and also
      the advantages and prospects of radical surgery in respect of possible patient
      survival.

PMID- 14579187
TI  - [Medizip surgical zipper: a new form of non-invasive wound closure with a
      surgical zipper].
AB  - PURPOSE: We describe the use of a new, non-invasive skin closure system (Medizip,
      Nycomed Pharma GmbH, Ismaning, Germany) in urological procedures. MATERIALS AND
      METHODS: Between July and November 2002, 23 patients received non-invasive skin
      closure with a Medizip surgical zipper after urological procedures (13 radical
      prostatectomies, 3 suprapubic prostatic enucleations, 3 ablatio testis and 1
      lumbal nephrectomy). Wound inspection was performed on day 3, day 8 and 6 weeks
      postoperatively. RESULTS: No wound complication such as infection or separation
      occurred. Wound dehiscence was seen in two patients (2 and 3mm). The zipper was
      removed routinely on day 8 after surgery. Of the 23 patients, 22 were pleased
      with the cosmetic results and rated the Medizip agreeable to wear. CONCLUSIONS:
      The Medizip surgical zipper is a safe, cosmetically satisfactory, cost-effective
      and time-sparing alternative to conventional suture material for skin closure.

PMID- 14579188
TI  - [Bladder exstrophy-epispadias complex: management and preliminary results].
AB  - PURPOSE: Retrospective evaluation of operative techniques and perioperative
      management as related to the primary anatomical and functional situation as well
      as analysis of the preliminary postoperative results regarding kidney function,
      continence and complications. MATERIALS AND METHODS: From October 1992 to April
      2003, 21 patients with bladder exstrophy-epispadias complex were treated,
      consisting of 12 children with untreated exstrophy and 9 who had undergone
      unsuccessful previous operations. Single-stage complete repair using the Erlangen
      concept was done during the first weeks of life in 8 infants and before school
      age in 3 children. One 13 year old girl had received a primary Mainz pouch II.
      The 9 unsuccessfully operated patients required a variety of different
      operations. The mean follow-up of 17 regularly controlled children was 62 months
      (range 3 to 129 months). RESULTS: In all children global kidney function remained
      stable, while reflux or obstruction was responsible for impaired unilateral split
      function ranging between 31 % and 45 % in 5. Four children were continent day and
      night after complete single-stage repair, 4 after ureterosigmoidostomy or Mainz
      pouch II and 5 after augmentation. CONCLUSIONS: In the newborn with previously
      untreated exstrophy-epispadias, we recommend single-stage complete functional
      reconstruction within the first weeks of life. Continence without loss of kidney
      function can be achieved in 50 % of these children. If adequate bladder capacity
      and continence cannot be achieved, an augmentation procedure or Mainz pouch II is
      our method of choice.

PMID- 14579189
TI  - [Paraneoplastic hyperthyroidism in a patient with metastasizing teratocarcinoma
      and excessively high HCG].
AB  - Clinically manifest hyperthyroidism is a rare paraneoplastic syndrome in patients
      with excessive HCG production due to testicular cancer. A 40-year-old patient
      with right testicular cancer (teratoma, embryonal cell carcinoma), diffuse
      pulmonary metastases and high serum HCG levels presented with symptomatic
      hyperthyroidism. The patient received immediately thyrostatic therapy and 4
      cycles of PEI chemotherapy (Cisplatin, Etoposide, Ifosfamide). Thyroid function
      had returned to normal by the beginning of the second course of chemotherapy.
      After right orchiectomy and resection of residual pulmonary masses which revealed
      vital tumor cells, two additional courses of chemotherapy were performed. The
      patient is well and without evidence of disease 11 months after therapy. All
      patients with testicular cancer and excessive HCG production should be evaluated
      for biochemical and clinical signs of hyperthyroidism and treated accordingly
      with antithyroidal medication and immediate cytoreductive chemotherapy.

PMID- 14579190
TI  - [Urinary ascites and perirenal urinoma - a renoprotective "Complication" of
      posterior urethral valves].
AB  - We report on a male newborn with urinary ascites and perirenal urinoma due to
      calyceal rupture caused by bladder outlet obstruction and posterior urethral
      valves. Despite the presence of left-sided high-grade reflux, the "pop-off"
      mechanism occurred in the non-refluxing right kidney. Impressive normalization of
      the upper urinary tract anomalies and renal function occurred after surgical
      treatment of the valves and removal of obstruction.

PMID- 14579191
TI  - [Metachronous testicular tumor of an extragonadal germ cell tumor].
AB  - INTRODUCTION: Approximately 5 - 7 % of germ cell tumors are of extragonadal
      origin. Biology and genetics are unclear, especially when the primary location is
      in the retroperitoneum. Chemotherapy is the initial treatment of choice for
      extragonadal germ cell tumors (EGGCTs), followed by surgical resection of the
      residual tumor mass. A primary testicular tumor must be ruled out by sonographic
      investigation and biopsy. The rate of metachronous testicular cancer in men with
      primary EGGCT is largely unknown. CASE REPORT: We present the first patient in
      the literature who developed a metachronous testicular cancer 10 months after
      primary occurrence of EGGCT in the retroperitoneum. CONCLUSIONS: This case report
      emphasizes the importance of follow-up examinations of patients with primary
      EGGCTs. They should include careful sonographic investigation of the testis in
      order to detect metachronous testicular cancer early. Suspicious findings require
      open surgery biopsy. Intraoperative histopathology can be false-negative for
      cancer detection, as an immunohistochemical examination is not available.

PMID- 14579193
TI  - Teaching clinical judgment in Taiwan.
AB  - Clinical judgment is a process that nurses use during the course of their daily
      practice to gather and to evaluate data, define the needs of the clients, and to
      judge the outcome of patient care. Such judgment is also a critical ability used
      to assess the progress of nursing students. The purpose of this qualitative
      research was to describe the clinical judgment teaching in nursing education in
      Taiwan and provide baseline data for future nursing students to learn in a more
      effective way. Data was collected by in-depth individual interviews of 10
      participants, all of whom were senior nursing faculty members from different
      nursing subspecialties. Two findings were reached. First, clinical judgment
      included not only the cognitive and the psychomotor domain of learning, but also
      the affective domain of reasoning. Second, due to cultural differences, "
      intuition " had never been mentioned in Taiwan, but a similar concept was
      substituted by use of the term " experience ". The findings suggested a holistic
      and integrative perspective was needed when teaching clinical judgement in
      Taiwan.

PMID- 14579192
TI  - Relationships between nurse staffing and patient outcomes.
AB  - Nursing studies have shown that nursing care delivery changes affect staff and
      organizational outcomes, but the effects on client outcomes have not been studied
      sufficiently. The purpose of this study was thus to examine the effect of nurse
      staffing variables- daily average hours of care, ratio of RNs to average patient
      census, workload, and skill mix- on patient outcomes as measured by five adverse
      occurrences. The adverse patient occurrences included unit rates of patient
      falls, pressure ulcers, respiratory and urinary tract infections, and
      patient/family complaints. Variables were measured retrospectively using
      consistently available data from each month of fiscal year 2000 from 21 medical
      surgical nursing care units in a 1394-bed medical center in Taiwan. Data were
      analyzed by descriptive and multivariate inferential statistics while controlling
      for patient acuity level. Results showed that workload of nurses is the most
      powerful predictor of nosocomial infections and hours of care best predicted the
      five adverse patient outcome indices. Lower adverse outcome rates were more
      consistently related to a higher proportion of N3 level of RNs. Patients could
      fare better when N3s play a significant role in the staffing mix. The findings
      provide further empirical support for the context of implications that patient
      outcomes are correlated to organizational structure. It obviously illustrates the
      relationships between nurse staffing and the quality of nursing practice.

PMID- 14579194
TI  - Life and health concerns of Indonesian women in transnational marriages in
      Taiwan.
AB  - The number of transnational marriages between Taiwanese men and Southeast Asian
      women is increasing rapidly in Taiwan. Approximately one out of nine marriages in
      Taiwan is transnational. The rapid increase the number of foreign brides has
      greatly transformed Taiwan's social and demographic structures. This study
      focuses on Indonesian brides, the second largest immigrant group in Taiwan, to
      explore their life and health concerns. In-depth interview assisted by
      participant observation for a qualitative study was used in this study. Fifteen
      women participated in the study. Content analysis was used for data analysis.
      Findings revealed life and health concerns of immigrant Indonesian women in
      Taiwan could be categorized into four themes: immigrant adaptation, communication
      difficulty, family continuity, and barriers to healthcare system utilization.
      Based on the findings of this study, suggestions are made for healthcare and
      health policies. Moreover, healthcare professionals should understand that
      designing and providing culturally sensitive and appropriate healthcare to these
      women is very important for promoting their and their children's health.

PMID- 14579195
TI  - Construct validity of the prenatal attachment inventory: a confirmatory factor
      analysis approach.
AB  - The purpose of this study was to test the construct validity of the Prenatal
      Attachment Inventory (PAI) by using Confirmatory Factor Analysis (CFA). The PAI
      was developed by Muller (1989, 1993), and consists of 21 Likert-type items
      arranged on a 4-point response set ranging from " almost always " to " almost
      never. " A sample of 349 pregnant women in their third trimester was recruited
      from obstetrical outpatient and inpatient centers, including high-risk and low
      risk pregnancy units, and childbirth education classes. Confirmatory factor
      analysis of the instrument yielded the result that all items have a significant
      factor loading. There were no negative error variances, no factor correlations
      greater than one, and no extremely large error variance. The indicator
      reliabilities ranged from.2 to.5. Moreover, the correlation matrix indicated that
      all PAI items were significantly related to one another at p <.01. These 21 items
      explained 79 % of variance in maternal fetal attachment (MFA). The overall
      measurement model fit indices showed that the hypothesized model fit the data
      well after two modifications (  2/df = 2.12, standardized root mean square
      residual =.05, goodness-of-fit index =.90, critical N = 204.5). The findings
      indicate that Muller's PAI is a valid instrument for research with pregnant
      women. Researchers can use this instrument for future research studies in the
      health care of pregnant women. Nursing educators and clinicians can use this
      instrument to assess expectant mothers' level of MFA.

PMID- 14579196
TI  - Development and testing of an instrument to measure interactions in synchronous
      distance education.
AB  - The advance of computer and network technology has made it possible for students
      to flexibly acquire real-time information through distance education, allowing
      life-long learning. As in previous studies, the researchers found that students
      generally experienced less instructional interaction in distance education as
      compared to the traditional classroom setting. The purpose of this study was to
      develop and test a reliable and valid instrument to evaluate instructional
      interactions in synchronous distance education. Based on a literature review and
      researcher experience, a 36-item interaction scale was developed and administered
      to 100 students from two different schools. Data were collected and the
      reliability and validity of the scale were tested. The results showed that the
      scale had a Cronbach's alpha coefficient of 0.901. Factor analysis was used to
      test the construct validity and 29 items were extracted and divided into seven
      different interaction factors. These seven factors explained 72.69 % of the total
      variance. Furthermore, the results showed that the scale had good internal
      consistency and construct validity, and would therefore provide an effective and
      useful tool for evaluating interaction in synchronous distance education. Use of
      this instrument can help teachers to understand interactions taking place in a
      synchronous distance education environment and provide guidance for the future
      development of distance education programs for various disciplines.

PMID- 14579197
TI  - Effects of using a nursing crisis intervention program on psychosocial responses
      and coping strategies of infertile women during in vitro fertilization.
AB  - Infertility and its treatment may cause life crises in infertile women. The
      purpose of this study is to evaluate the effects of a crisis intervention program
      on improving psychosocial responses and enhancing coping strategies for infertile
      women attending different stages of an In-Vitro Fertilization V Embryo Transfer
      (IVF-ET) treatment program. Using an experimental study design, infertile women
      attending an IVF-ET treatment program were randomly assigned to experimental and
      control groups. In the experimental group, infertile women completed and answered
      a questionnaire and received nursing crisis intervention at the initial stage of
      treatment (day 3). This included (1). viewing a video explaining the therapeutic
      process of IVF-ET, (2). self-hypnosis and muscle relaxation training, and (3).
      provision of cognitive-behavioral counseling. The same questionnaire was used
      again for subjects at the stage of embryo transfer and before taking a pregnancy
      test. The women in the control group were only interviewed using the same
      questionnaire and at the same times as the experimental group. Analysis by
      repeated measurement ANOVA demonstrated that there was a reduction in
      psychosocial response in terms of interpersonal relationships, and there was an
      interaction between intervention effects and stage of treatment. However, there
      was no statistically significant difference in the level of psychosocial
      responses between the experimental and control groups although some meaningful
      findings were made. However, in terms of state of anxiety, confrontational
      problems, and isolated mind/body relaxation, there were significant differences
      between the two groups of infertile women at some stages of IVF-ET treatment. The
      women in the experimental group perceived a positive effect of the nursing
      intervention in relieving their psychosocial responses. The results of this
      nursing crisis intervention could be helpful in nursing practice when dealing
      with infertile women attending IVF treatment programs.

PMID- 14579198
TI  - Effects of music therapy on oxygen saturation in premature infants receiving
      endotracheal suctioning.
AB  - The purpose of this study was to investigate how premature infants' oxygen
      saturation changed in response to music therapy while they were receiving
      endotracheal suctioning. A convenience sample of 30 premature infants was
      selected from three neonatal intensive care units. A one-group repeated measures
      design was adopted for this study. The oxygen saturation of all subjects was
      first measured while they were receiving endotracheal suctioning during a four
      hour control period with regular care. Then, four hours after the control period
      was completed, an experimental period began in which the music " Transitions "
      was played. One minute before suctioning, the level of oxygen saturation was
      measured to provide the baseline data. During a period of 30 minutes after
      suctioning, the oxygen saturation was recorded every minute to analyze the
      clinical effects of music therapy. The results showed that premature infants
      receiving music therapy with endotracheal suctioning had a significantly higher
      SPO(2); than that when not receiving music therapy (p <.01), and the level of
      oxygen saturation returned to the baseline level faster than when they did not
      receive music therapy (p <.01). Accordingly, it is hoped that giving appropriate
      music therapy as developmental care to premature infants when performing any
      nursing intervention may enhance not only the quality of nursing care but also
      quality of the infant's life.

PMID- 14579199
TI  - Quality of life and related factors for people living with HIV/AIDS in Northern
      Taiwan.
AB  - The purpose of this study was to identify the variables related to quality of
      life in the population of individuals living with HIV/AIDS (PLWHA) in Taiwan.
      Purposive sampling was used to identify subjects from the outpatient departments
      (OPD) of three teaching hospitals and one sexually transmitted disease (STD)
      clinic in the Taipei area. For this study, the questionnaire included a
      demographic data sheet, physical-symptom distress and mood-disturbance scales, a
      personal-resource questionnaire (PRQ85-II) and a quality-of-life index (QLI). A
      total of 114 subjects completed the questionnaire. The results revealed that
      higher quality of life was associated with less mood disturbance (r = -.72; p
      <.001), reduced physical-symptom distress (r = -.47; r <.001), and higher levels
      of social support (r =.57; p <.001). PLWHA life quality was reflected accurately
      by mood disturbance, social support, physical-symptom distress, self-perceived
      mode of HIV transmission, and major source of financial support. These variables
      accounted for 60.9 % of QOL variance. As mood disturbance was the strongest
      predictor of quality of life, psychosocial intervention for mood disturbance
      should be emphasized and developed in future studies.

PMID- 14579200
TI  - Worksite health promotion -- on the effects of an employee fitness program.

PMID- 14579201
TI  - [Epidemology and treatment of depressive disorders].
AB  - 5-10% of the general population suffer from depressive disorders, one third of
      which are chronic. Depression impairs the quality of life, and 30.8% of patients
      show reduced working capacity. Patients are on average 10.9 days per month on
      sick leave. About half of the depressed patients undergo treatment, contacting
      general practitioners at an average of 14.5 times, psychotherapists 2 times and
      psychiatrists 1.4 times per year. Approximately 100 million daily doses of
      specific antidepressants are prescribed per year in Germany, an amount enough to
      treat 1% of the general population, which is indicative of an insufficient
      treatment rate. Pharmacotherapy has been found to be more effective than
      psychotherapy in acute episodes. However, psychotherapy patients show better long
      term results in respect to relapses and social adaptation. Due to the large
      number of depressed patients, general practitioners are the primary therapists.
      Referral to psychiatrists or psychotherapists is indicated in cases of chronic
      and complicated courses.

PMID- 14579202
TI  - [Neurotic depression--a disease without a diagnosis or a diagnosis without a
      glossary? ].
AB  - With the transition from ICD-9 to ICD-10 the diagnosis of neurotic depression was
      omitted. Freyberger showed that this diagnosis in the ICD-10 was replaced mainly
      by the diagnoses of dysthymia, recurrent depression and depressive episode (with
      this ranking of frequency). A renowned German psychiatrist criticized this change
      as replacing an unsubstantiated dichotomic with an unsubstantiated dimensional
      model. The same was the case with the change from DSM-II to DSM-III: Torgersen
      criticized here that the heterogeneous diagnosis of neurotic depression was
      basically replaced by the similarly heterogeneous diagnosis of major depression.
      The underlying rationale behind the omission of the traditional diagnosis of
      neurotic depression in the new glossaries must be seen in the critical
      contributions of such renowned researchers as Winokur, Klerman and Akiskal during
      the 60's and 70's of the last century. The present work compares these
      exclusively phenomenological approaches to classification with a psychodynamic
      approach, and the author defends the possibility of operationalizing such an
      attempt as validly as a mere descriptive one. This view is supported by the
      successful work of a group of German scientists in promoting the OPD
      (operationalized psychodynamic diagnostics) system. Operationalizable elements
      are not only to be found in the critics' own contributions, but in recent
      empirical studies on dysthymia and the other subsequent diagnoses as well. An
      operationalized and verifiable diagnosis of neurotic depression would have to go
      far beyond the two main criteria of the ICD-9 (psychoreactive genesis, exclusion
      of psychosis) and include new insights and perspectives; this, however, is
      considered feasible. It must be recognized that there is no place in the
      prevailing diagnostic scene for such a diagnostic construct. Perhaps with time
      diagnostic modes will change, as has often been the case in the past.

PMID- 14579203
TI  - [Etiological models and therapeutic techniques in the psychodynamic treatment of
      depression].
AB  - Psychodynamic treatment of depression is described as a problem-centered approach
      which is derived from the etiological model. This treatment is conceptually based
      on the internalisation of problematic relationship patterns, the development of
      structural vulnerability, and the formation of specific coping patterns. The
      therapeutic interventions specific to depression treatment deal with the present
      state of vulnerability and the tendency to overstrain oneself, which are the
      result of depressive personality development and which support new relationship
      experiences. Special emphasis is placed on the specific therapeutic attitude
      which allows treatment particularly of interpersonal problems by reflecting,
      supporting and confronting. Psychodynamic depression treatment is problem
      centered in that it is tailored to the specifically problematic kinds of
      relationship expectations and relationship problems as well as the related
      problems of self esteem.

PMID- 14579204
TI  - [Relapse in depressive disorders--is there a need for maintenance psychotherapy?
      ].
AB  - OBJECTIVES: Patients with depressive disorders who enroll in typical short-term
      clinical studies have a high risk of early relapse (30-70 %) and chronicity (ca.
      20 %). Factors which contribute to this risk are residual symptoms at
      termination, previous recurrent episodes, chronic stress, etc. Pharmacological
      strategies offer a multitude of means of relapse prevention, while in
      psychotherapeutic interventions there is a dearth of such recommendations.
      Studies on relapse-preventing continuous contacts (maintenance therapy), for
      example, are very rare. METHODS: We present empirical data on risk factors for
      early relapse and chronic course in depressive disorders together with general
      strategies for relapse prevention. Results of controlled studies with maintenance
      psychotherapy will then be reported. RESULTS: Psychotherapeutic maintenance
      strategies have been shown to be successful in several controlled studies.
      Furthermore, recent studies show typical moderating mechanisms for better
      resilience against stressors in formerly depressed patients. The typical setting
      under study was monthly sessions over a period of at least 8 months and up to
      three years. In case of severe risk factors continuous pharmacotherapy also has
      to be taken into consideration. DISCUSSION: The issue is discussed in respect to
      differential indication (primarily long-term therapy vs. a rather quick change to
      maintenance contacts of low frequency). Moreover, the ethical questions of
      inadequate dependency as well as the clinical aspects of transference
      countertransference dynamics are viewed.

PMID- 14579205
TI  - [The importance of depressive disorders in somatic medicine].
AB  - Depressive disorders--including mild and subthreshold forms--are frequent in
      medical patients, although often not recognized. Over the past decades
      accumulating scientific evidence has demonstrated their clinical relevance.
      Depressive disorders and also elevated scores on self-rating scales for
      depressive symptoms are clearly related to disease behavior and quality of life.
      In many physical conditions they also predict adverse outcome, including
      premature death. This paper gives an overview of the literature on the relevance
      and treatment of comorbid depression in patients with HIV infection, cancer and
      coronary heart disease. It shows that the subjective effects of depression are
      rather similar in different somatic conditions. In addition, depression also
      interacts with the physical course of different diseases. However, the specific
      physiological mediators involved vary among different somatic diseases and have
      not yet been completely understood. Despite this uncertainty an improved
      recognition and treatment of comorbid depression can be recommended. Supportive
      interventions focussing on coping demands as well as regular psychotherapy and in
      some cases antidepressant medication may be indicated. While it still appears
      premature to establish generally applicable treatment guidelines, an
      individualized approach with regard to the different treatment alternatives for
      individual patients should be advocated.

PMID- 14579206
TI  - [Infant moods and the chronicity of depressive symptoms: the co-creation of
      unique ways of being together for good or ill. Paper 1: The normal process of
      development and the formation of moods].
AB  - The ontogenesis of moods and the process that establishes them is addressed.
      Moods arise out of normal developmental processes at both a macro- and micro
      developmental level. Moods are part of normal development as well as a component
      of pathological processes and they are a ubiquitous presence that gives meaning
      to experience in infant and adult during daily life and therapy. In this first
      part of a two-part paper I will address the normal development of moods; in the
      second part I will to address issues related to psychopathology and therapy,
      especially depression and the intergenerational transfer of mood. I argue that
      moods are dyadic phenomena--something that develops out of the chronic co
      creative interactions of two individuals--rather than solely being an
      intrapsychic process. I will also argue, especially when one considers the
      development of moods in infants, that moods make sense of the world as components
      of states of consciousness that give unique meaning to the individual's
      engagement with the world and further that moods function to bring the past into
      the present.

PMID- 14579207
TI  - Economics in the cardiac surgical ICU: changing times may bring friction.

PMID- 14579208
TI  - The economic benefit of organizational restructuring of the cardiothoracic
      intensive care unit.
AB  - OBJECTIVES: Compare cost/benefits of organizational restructuring of the cardiac
      intensive care unit (CICU). DESIGN: Prospective, with a retrospective control
      period. SETTING: Academic medical center. PARTICIPANTS: Sixty-six CICU patients
      (prospective) and 57 patients who received care before restructuring
      (retrospective) were compared. Entrance criteria were constant for both study
      periods. INTERVENTIONS: The CICU was restructured from a level III ICU to a level
      I ICU with the initiation of a consultant CICU service. The CICU service provided
      an attending physician dedicated to ICU care daily. All cardiac patients admitted
      into the CICU received consultation by the CICU service. MEASUREMENTS AND MAIN
      RESULTS: The average postoperative intubation time decreased during the
      intervention period (61% extubated within 6 hours v 12%, p = 0.004). Pharmacy,
      radiology, laboratory, and ICU costs decreased 279 US dollars (p = 0.004), 196 US
      dollars (p = 0.003), 190 US dollars (p = 0.15), and 470 US dollars (p = 0.12),
      respectively. The ICU length of stay (0.28 days shorter) as well as the overall
      postsurgery stay (0.54 days shorter) were reduced in the intervention period (p =
      0.11 and 0.10, respectively). CONCLUSIONS: The CICU service significantly reduced
      both total ICU-related costs ($1,173/patient) and overall costs (2,285 US
      dollars/patient) during the intervention period. Professional fees only reduced
      overall savings by 8%. These results indicate that organizational restructuring
      of the CICU to newer models can reduce costs associated with cardiac surgery.

PMID- 14579209
TI  - Clinical experience with adaptive support ventilation for fast-track cardiac
      surgery.
AB  - OBJECTIVE: To evaluate adaptive support ventilation (ASV), an automatic
      microprocessor-controlled mode of mechanical ventilation, for the initial
      ventilatory management in consecutive patients eligible for early extubation
      after cardiac surgery. DESIGN: Prospective observational study. SETTING:
      Nonuniversity cardiac center. PARTICIPANTS: One hundred fifty-five consecutive
      patients eligible for early tracheal extubation after cardiac surgery.
      INTERVENTIONS: On intensive care unit arrival, patients were ventilated by
      adaptive support ventilation. This mode provided an automatic selection of
      initial ventilatory parameters and a continuous adaptation to patient's
      respiratory activity, guaranteeing that a preset minute ventilation was
      delivered. Once the patients had recovered sustained spontaneous ventilation, the
      ventilator was switched manually to pressure support for the terminal part of
      respiratory weaning followed by extubation. MEASUREMENTS AND MAIN RESULTS: In
      adaptive support ventilation, all patients could be ventilated satisfactorily
      except 1; tidal volume was 8.7 +/- 1.4 mL/kg of ideal body weight (mean +/- SD),
      plateau pressure was 20.3 +/- 3.9 cmH(2)O, and arterial blood gas measurements
      were satisfactory. One hundred thirty-four patients (86%) were extubated within 6
      hours, and intubation time was 3.6 (2.53-4.83) hours (median, [quartiles]). No
      reintubation because of respiratory failure was required. Adaptive support
      ventilation was considered easy to use by both the nurses and physicians.
      CONCLUSIONS: Adaptive support ventilation was used in a group of 155 consecutive
      patients after fast-track cardiac surgery. This ventilation mode was safe, easy
      to apply, and allowed rapid extubation in suitable patients. ASV may facilitate
      postoperative respiratory management.

PMID- 14579210
TI  - ICU sedation after coronary artery bypass graft surgery: dexmedetomidine-based
      versus propofol-based sedation regimens.
AB  - OBJECTIVE: To compare dexmedetomidine-based to propofol-based sedation after
      coronary artery bypass graft (CABG) surgery in the intensive care unit (ICU).
      DESIGN: Randomized, open label. SETTING: Twenty-five centers in the United States
      and Canada. PARTICIPANTS: Two hundred ninety-five adults undergoing CABG surgery.
      INTERVENTIONS: At sternal closure, patients in group A received 1.0 microg/kg of
      dexmedetomidine over 20 minutes and then 0.2 to 0.7 microg/kg/h to maintain a
      Ramsay sedation score > or =3 during assisted ventilation and > or =2 after
      extubation. Patients could be given propofol for additional sedation if
      necessary; group B patients received propofol-based care according to each
      investigator's standard practice. MEASUREMENTS AND MAIN RESULTS: Mean sedation
      levels were within target ranges in both groups. Mean times to weaning and
      extubation were similar, although fewer dexmedetomidine patients remained on the
      ventilator beyond 8 hours. Morphine use was significantly reduced in the
      dexmedetomidine group. Only 28% of the dexmedetomidine patients required morphine
      for pain relief while ventilated versus 69% of propofol-based patients (p <
      0.001). Propofol patients required 4 times the mean dose of morphine while in the
      ICU. Mean blood pressure increased initially in both groups, then decreased to 3
      mmHg below baseline in dexmedetomidine patients; mean arterial pressure remained
      at 9 mmHg above baseline in propofol patients. No ventricular tachycardia
      occurred in the dexmedetomidine-sedated patients compared with 5% of the propofol
      patients (p = 0.007). Respiratory rates and blood gases were similar. Fewer
      dexmedetomidine patients received beta-blockers (p = 0.014), antiemetics (p =
      0.015), nonsteroidal anti-inflammatory drugs (p < 0.001), epinephrine (p =
      0.030), or high-dose diuretics (p < 0.001). CONCLUSION: Dexmedetomidine provided
      safe and effective sedation for post-CABG surgical patients and significantly
      reduced the use of analgesics, beta-blockers, antiemetics, epinephrine, and
      diuretics.

PMID- 14579211
TI  - Prevalence of risk factors, and not gender per se, determines short- and long
      term survival after coronary artery bypass surgery.
AB  - OBJECTIVE: Much attention has been directed towards female gender as an
      independent risk factor for in-hospital mortality after coronary artery bypass
      grafting surgery; however, the effects of surgery are known to persist for 6
      months or more. Studies that have compared postoperative survival in women and
      men beyond hospital discharge report disparate results with regard to the
      independent effect of gender per se on ultimate survival. DESIGN: This
      investigation was a prospective, observational study. SETTING: The study was a
      multicenter investigation involving 24 US medical centers. PARTICIPANTS: There
      were 2,048 patients undergoing isolated coronary artery bypass graft surgery
      enrolled between September 1991 and September 1993 and after discharge.
      INTERVENTIONS: There were no interventions with this prospective observational
      study. MEASUREMENTS AND MAIN RESULTS: Preoperative demographic variables, medical
      history, and angiographic data were collected for each patient at the time of
      enrollment. Patients' vital status through the National Death Index up to August
      31, 1998, were added to assess postoperative long-term survival. For survivorship
      analysis, the Kaplan-Meier product-limit method was used with Cox regression
      model. Survivorship analyses were performed separately and in combination on
      mortality within 30 days and 6 months of coronary artery bypass graft surgery and
      during the entire postoperative follow-up period. Among women, preoperative
      disease status, as expected, was more severe than that in men. Women were older
      (p = 0.0001) and had more comorbidity, such as congestive heart failure (p =
      0.0019), diabetes (p = 0.0001), anemia, and hypertension (p = 0.0001). After
      surgery, unadjusted survival of 6 months and 5 years in women was worse than that
      in men. However, there were no gender-related differences in short- or long-term
      survival after adjusting for covariates in the multivariate model. Preoperative
      conditions, such as congestive heart failure, anemia, diabetes, and advanced age,
      are indicative of greater risk in both women and men for lower survival after
      coronary artery bypass graft surgery. CONCLUSIONS: Disease prevalence in women,
      and not gender per se, affects mid- and long-term survival after cardiac surgery.
      Attention, therefore, should be focused on efforts to reduce or modify such
      disease prevalence earlier in women, which may in turn allow longer survival
      after surgical intervention. Differences in postoperative survival between women
      and men were related to the gender differences in the distribution of
      preoperative risk factors.

PMID- 14579212
TI  - Emergency and elective coronary artery bypass grafting: comparisons of risk
      profiles, postoperative outcomes, and resource requirements.
AB  - OBJECTIVE: To investigate the association between preoperative risk factors and
      postoperative outcomes in emergency and elective coronary artery bypass graft
      (CABG) patients and to quantify resource requirements. DESIGN: Retrospective
      database review. SETTING: New York State SPARCS database. PARTICIPANTS: Data from
      4,001 emergency and 7,489 elective CABG patients were evaluated retrospectively.
      INTERVENTIONS: Data were compared between groups using chi-squares, t tests, and
      logistic regression analysis. MEASUREMENTS AND MAIN RESULTS: Preoperatively,
      47.1% of patients in the emergency group had unstable angina and 34.1% had acute
      myocardial infarction compared with 33.9% and 15.2% in the elective group,
      respectively (p < 0.0001). There were no marked differences in the preoperative
      noncardiac risk factors between groups. The mortality rate was 4.7% in the
      emergency group and 2.6% in the elective group (p < 0.0001). The emergency group
      had more postoperative cardiac complications (18.3% v 8.3%, p < 0.0001). The
      length of hospital stay in the emergency group was 17.5 +/- 15.8 days (median 14
      days) compared with 12.9 +/- 15.1 days (median 9 days) in the elective group (p <
      0.00001). Total hospital charges in the emergency and elective groups were 46,700
      US dollars +/- 42,400 US dollars (median 35,600 US dollars ) and 34,800 US
      dollars +/- 36,400 US dollars (median 26,500 US dollars) (p < 0.00001),
      respectively. The median total cost was 26,300 US dollars for emergency and
      19,600 US dollars for elective group (p < 0.00001). CONCLUSION: Patients
      undergoing emergency CABG had greater postoperative morbidity and mortality,
      longer LOS, and higher total costs than patients undergoing elective surgery.
      This difference is predictable on the basis of preoperative cardiac risk factors.
      Emergency operations have a major impact on the rates of morbidity, mortality,
      and use of resources.

PMID- 14579213
TI  - Biochemical markers of cerebrospinal ischemia after repair of aneurysms of the
      descending and thoracoabdominal aorta.
AB  - OBJECTIVE: To investigate the clinical potential of several markers of spinal
      cord ischemia in cerebrospinal fluid (CSF) and serum during aneurysm repair of
      the descending thoracic or thoracoabdominal aorta. DESIGN: Observational study of
      consecutive patients. Nonblinded, nonrandomized. SETTING: University hospital
      thoracic surgical unit. PARTICIPANTS: Eleven consecutive elective patients.
      INTERVENTIONS: Distal extracorporeal circulation and maintenance of CSF pressure
      <10 mmHg until intrathecal catheter removal. MEASUREMENTS AND MAIN RESULTS: CSF
      and serum levels of S100B (and its isoforms S100A1B and S100BB), neuronal
      specific enolase (NSE), and the CSF levels of glial fibrillary acidic protein
      (GFAp) and lactate were determined. Two patients had postoperative neurologic
      deficit. One with a stroke showed a 540-fold increased GFAp, a 6-fold NSE, and
      S100B increase in CSF. One with paraplegia had a 270-fold increase in GFAp, a 2
      fold increase in NSE, and 5-fold increased S100B in CSF. One patient without
      deficit increased GFAp 10-fold, NSE 4-fold, and S100B 23-fold in CSF. CSF lactate
      increased >50% in 6 of 9 patients without neurologic deficit. Serum S100B
      increased within 1 hour of surgery in all patients without any concomitant
      increase in CSF. S100A1B was about 70% of total S100B in both serum and CSF in
      patients with or without neurologic defects. S100B in CSF increased 3-fold in 3
      of 9 asymptomatic patients. CONCLUSIONS: In patients with neurologic deficit,
      GFAp in CSF showed the most pronounced increase. Biochemical markers in CSF may
      increase without neurologic symptoms. There is a significant increase in serum
      S100B from surgical trauma alone without any increase in CSF.

PMID- 14579214
TI  - Nicardipine or nitroglycerin in patients with failed percutaneous coronary
      angioplasty: effect on myocardial diastolic function.
AB  - OBJECTIVE: To evaluate whether intracoronary vasodilators can improve diastolic
      function in 32 patients with failed percutaneous transluminal coronary
      angioplasty (PTCA). DESIGN: Clinical trial. SETTING: Single-institution, academic
      hospital. PARTICIPANTS: Failed PTCA patients undergoing emergency coronary artery
      bypass grafting surgery. INTERVENTIONS: Patients were divided into 2 groups:
      group A received 0.1 mg of intracoronary nicardipine, and group B received 20
      microg of intracoronary nitroglycerin. Both drugs were administrated via a
      coronary dilatation perfusion catheter inserted in the catheterization laboratory
      by the cardiologist. Subsequently, they were continuously infused via the side
      port of the introducer of the pulmonary artery catheter and titrated to keep
      systolic blood pressure at about two thirds of the control value. Transesophageal
      echocardiography (Power Vision/6000, 9-mm 5MHZ Probe; Toshiba, Elmsford, NY) was
      used in this study. MEASUREMENTS AND MAIN RESULTS: Left ventricular ejection
      fraction, cardiac index, tissue Doppler imaging velocity of the left ventricle
      and mitral annulus, and troponin levels were measured before and after
      administration of the 2 vasodilators and after cardiopulmonary bypass. Diastolic
      dysfunction was found preoperatively in all the patients and responded only to
      intracoronary nicardipine. Ea of mitral annulus velocity significantly increased
      in group A patients from 7.5 +/- 0.02 to 11.8 +/- 0.01 (p < 0.005) and decreased
      in group B patients from 8.0 +/- 0.03 to 7.5 +/- 0.02 after nicardipine or
      nitroglycerin administration. Left ventricular ejection fraction and cardiac
      index increased significantly (p < 0.005) only after nicardipine administration.
      Troponin levels were significantly lower in group A than in group B patients (p <
      0.005). CONCLUSION: Intracoronary nicardipine improves diastolic function and
      myocardial flow velocity in patients with failed PTCA undergoing emergency
      coronary artery bypass graft surgery.

PMID- 14579215
TI  - Implantable cardioverter-defibrillator placement in patients with mild-to-
      moderate left ventricular dysfunction: hemodynamics and recovery profile with two
      different anesthetics used during deep sedation.
AB  - OBJECTIVE: To compare the effects of thiopental and propofol during
      defibrillation threshold testing (DFT) on hemodynamics and recovery profile in
      patients requiring automatic internal cardioverter-defibrilator placement.
      DESIGN: Prospective clinical investigation. SETTING: University hospital.
      PARTICIPANTS: Thirty-four adult patients. INTERVENTIONS: After administration of
      midazolam, 0.025 mg/kg, and fentanyl, 0.5 to 1 mug/kg, surgery was performed
      under topical infiltration with 1% lidocaine. In group I (GI) (n = 17), patients
      received thiopental by slow injection and patients in group II (GII) (n = 17)
      received propofol before induction of ventricular fibrillation (VF). MEASUREMENTS
      AND MAIN RESULTS: Patients received 4.1 +/- 1.4 mg of midazolam, 114 +/- 34 mug
      of fentanyl, and 280 +/- 78 mg of thiopental in GI; and 4.6 +/- 1.7 mg of
      midazolam, 119 +/- 62 mug of fentanyl, and 147 +/- 40 mg of propofol in GII (p >
      0.05). Hemodynamics did not show significant differences between the groups at
      any recording time. Average time needed to regain the pretest sedation level was
      16.4 +/- 8.8 minutes in GI and 10.9 +/- 5.5 minutes in GII (p = 0.03). Time
      required to achieve a score of 10 using a modified Aldrete score was 26.4 +/- 9.3
      minutes in GI and 17.4 +/- 4.9 in GII (p = 0.001). Seven patients in GII (41%)
      and 1 patient in GI (6%) became hypotensive after DFT (p = 0.04). CONCLUSIONS:
      Deepening the sedation level by slow injection of thiopental or propofol before
      DFT provided satisfactory conditions during brief episodes of VF. Delay in
      recovery of arterial pressure after DFT with propofol and delay in arousal and
      discharge of patients with thiopental are major disadvantages of the regimens.

PMID- 14579216
TI  - Ventricular cardiac-assist devices in infants and children: anesthetic
      considerations.
AB  - OBJECTIVE: The application of a mechanical cardiac-assist device is now a common
      procedure in modern cardiac surgery in patients with end-stage failure, whereas
      in pediatric patients it is still a great challenge. In the recent literature, a
      broad range of survival and weaning rates have been reported, depending on the
      variety of mechanical devices and the choice of patients with different
      conditions before implantation or if the device is used in emergency surgery. In
      this article, the authors report their experience with pediatric cardiac-assist
      devices and the perioperative anesthesia management in this group of patients.
      PATIENTS AND METHODS: From 1997 to 2001, 11 infants and children were supported
      with a left and/or right ventricular-assist device. Diagnosis included
      myocarditis and complex cardiac malformations (hypoplastic left heart syndrome,
      tetralogy of Fallot with cardiomyopathy, and combined heart defects). The data
      sets of all patients were recorded using the online anesthesia record-keeping
      system NarkoData (IMESO GmbH, Huttenberg, Germany). The program collects all
      perioperative data during surgery and during a stay in the PACU, including vital
      signs, administered drugs, as well as the data set of the German Society of
      Anesthesiology and Intensive Care Medicine. RESULTS: All patients were divided
      into 2 groups: group 1 = survivors and group 2 = nonsurvivors. A total of 5
      patients were in group 1, and group 2 consisted of 6 patients. The duration of
      anesthesia in group 1 patients (173.2 +/- 95.1 minutes) was significantly (p <
      0.05) shorter than in group 2 (631.1 +/- 258.8 minutes) as well as the amount of
      packed red cells (group 1= 540.5 +/- 150.3 mL, group 2 = 880.6 +/- 400.3 mL).
      Cardiopulmonary bypass before implantation of a VAD was necessary only in 2
      patients from group 1, whereas 5 patients in group 2 were on pump during the
      procedure. The rate of aortic cross-clamping was also significantly lower in
      group 1 than in group 2 (p < 0.05). CONCLUSIONS: The surgical outcome depends on
      the patient's condition at the time of surgery. Emergency surgery, preoperative
      multiorgan failure, and the need for an extracorporeal circulation with aortic
      cross-clamping seem to predict a negative outcome in this group of patients.

PMID- 14579217
TI  - Anesthetic management of juvenile nasopharyngeal angiofibroma resection.
AB  - OBJECTIVE: To evaluate the anesthetic implications of the surgical resection of
      juvenile nasopharyngeal angiofibroma (JNA). DESIGN: Retrospective study. SETTING:
      University-affiliated community hospital. PARTICIPANTS: Ten patients undergoing
      resection of JNA. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data from
      the records of 10 patients undergoing resection of JNA were reviewed and analyzed
      with regard to demographics, history of the disease, characteristics of the
      tumor, surgical resection techniques, and anesthetic management. Patients were
      age 11 to 29 years. All had nasal obstruction as presenting symptom. There was no
      intracranial invasion. Eight tumors were resected via a lateral rhinotomy and 2
      endoscopically (after embolization of the tumor's feeding vessels). Duration of
      surgery was 6 +/- 1 hours for rhinotomy and 6 and 6.5 hours for the 2 endoscopic
      resections. Anesthesia was induced in a rapid-sequence manner. Arterial and
      central venous catheters were placed in all patients. Mean arterial pressure was
      targeted to 55 to 65 mmHg by using increasing concentrations of isoflurane. The
      estimated blood loss was 4,800 +/- 1,600 mL and blood replacement was 3,200 +/-
      1,400 mL in the first group. The 2 other patients lost 600 mL and 1,500 mL. Blood
      replacement in this group was 0 and 700 mL respectively. No mortality or major
      morbidity occurred. CONCLUSION: Resection of JNA should be considered a major
      procedure with many anesthetic challenges. Isoflurane may be employed to provide
      deliberate hypotension.

PMID- 14579218
TI  - Development of malignant hyperthermia post-cardiopulmonary bypass during surgery
      for mitral valve replacement.

PMID- 14579219
TI  - Thoracic epidural anesthesia as a bridge to redo coronary artery bypass graft
      surgery.

PMID- 14579220
TI  - Successful use of bivalirudin for cardiopulmonary bypass in a patient with
      heparin-induced thrombocytopenia.

PMID- 14579221
TI  - The wire-guided endobronchial blocker as a solution to provide one-lung
      ventilation when a double-lumen endotracheal tube is malpositioned.

PMID- 14579222
TI  - Bronchoscopic procedures for central airway obstruction.

PMID- 14579223
TI  - Elective cardiac anesthesia in a nonagenarian.

PMID- 14579224
TI  - Pro: Endovascular repair of abdominal aortic aneurysms reduces perioperative
      morbidity and mortality.

PMID- 14579225
TI  - Con: Endovascular stent repair for aortic aneurysm surgery is not associated with
      lower perioperative risk.

PMID- 14579226
TI  - Transesophageal echocardiography of a new paravalvular echolucent area after
      aortic valve replacement.

PMID- 14579229
TI  - Thoracic epidural analgesia and coronary artery bypass grafting.

PMID- 14579230
TI  - Diagnostic dilemma: Unexpected pressure waveform during pulmonary artery catheter
      placement: what is the dilemma?

PMID- 14579238
TI  - Mitoxantrone-cyclophosphamide-rituximab: an effective and safe combination for
      indolent NHL.
AB  - Treatment for extensive indolent lymphoma should combine optimization of efficacy
      without excessive toxicity. Rituxan may be an ideal agent for combinations with
      chemotherapy because of its non-cross-resistant toxicity profile and the
      potential for synergism. We present the results of 32 patients with indolent B
      cell NHL who received a novel three-drug combination designed with the intent of
      preservation of both efficacy and quality of life. Patient characteristics were
      as follows, median age, 58 years (36-75 years); histology, follicular 16, SLL/CLL
      five, lymphoplasmacytic six, marginal cell five; relapsed or refractory, 10;
      untreated, 22. Patients first received cyclophosphamide 800 mg/m(2) and
      mitoxantrone 8 mg/m(2), iv on the same day, every 3 weeks for two cycles.
      Subsequently, patients received rituximab followed by mitoxantrone 8 mg/m(2)
      every 2 weeks for four cycles. The regimen, and particularly rituximab, was
      extremely well tolerated. Grade I/II, infusion-related toxicity was noted in 10%.
      Six patients achieved a PR and 23 a CR for an overall response of 90% (95% CI: 79
      100%). The actuarial median TTP for all patients was 30 months. Molecular
      remissions were noted in 8/14 patients tested in CR. We conclude that the
      cyclophosphamide-mitoxantrone-rituxan (CyMiR) regimen is effective and extremely
      well tolerated. Furthermore, rituximab infusion-related morbidity is nearly
      completely eliminated.

PMID- 14579239
TI  - Primary non-Hodgkin lymphoma of the humerus following traumatic injury: case
      report.
AB  - A case of primary non-Hodgkin lymphoma of the right humerus which occurred in a
      21-year-old male patient after an impact to the right shoulder in a car accident
      in July 1983 is described. Seventeen years after the injury, due to a civil
      lawsuit, the biopsy material was revised. Immunohistochemical analysis showed
      CD20 and CD79a positivity on large pleomorphic cells, while small reactive
      lymphocytes were CD3, Bcl-2 and CD20 positive. Molecular analysis carried out
      with PCR revealed a monoclonal B-lymphocyte population. The diagnosis of diffuse
      large peripheral B cell lymphoma of the bone was confirmed. The present case
      concurs with the literature on primary bone lymphoma, in which the diagnostic
      problem, trauma-related presentation and an excellent prognosis of malignant
      tumour are emphasized.

PMID- 14579240
TI  - ABCG2 (BCRP) expression in normal and malignant hematopoietic cells.
AB  - ABCG2 (BCRP) is a member of the ATP-binding cassette (ABC) family of cell surface
      transport proteins. ABCG2 expression occurs in a variety of normal tissues, and
      is relatively limited to primitive stem cells. ABCG2 expression is associated
      with the side population (SP) phenotype of Hoechst 33342 efflux. The substrate
      profile of ABCG2 includes the antineoplastic drugs primarily targeting
      topoisomerases, including anthracyclines and camptothecins. More recently,
      pheophorbide, a chlorophyll-breakdown product, and protoporhyrin IX have been
      described as ABCG2 substrates, perhaps indicating a physiologic role of
      cytoprotection of primitive cells. Also, mice lacking ABCG2 expression have no
      intrinsic stem cell defects, although there is a remarkable increase in toxicity
      with antineoplastic drugs that are ABCG2 substrates, and also a photosensitivity
      resembling protoporphyria. Like other members of the ABC family, such as MDR1 and
      MRP1, ABCG2 is expressed in a variety of malignancies. Despite numerous reports
      of ABCG2 expression in AML, there is little evidence that ABCG2 expression is
      correlated with an adverse clinical outcome. This review will focus on the
      potential usefulness of ABCG2 as a marker primitive stem cells and possible
      physiologic roles of ABCG2 in protection of primitive stem cell populations, and
      potential methods of overcoming ABCG2-associated drug resistance in anticancer
      therapy.

PMID- 14579241
TI  - Long-term survival in patients with human immunodeficiency virus-associated small
      non-cleaved cell lymphoma: the role for short course intensive chemotherapy.
AB  - While intensive chemotherapy is recommended for the treatment of non-HIV related
      adult small non-cleaved lymphoma (SNCL), including Burkitt's and Burkitt-like
      lymphoma, optimal treatment for patients with HIV-associated SNCL is not known.
      We assessed remissions and survival in a cohort of 44 consecutive HIV positive
      patients diagnosed with SNCL at our hospital between June 2000 and November 2001
      using chart and pathology data. Median follow-up, survival and survival at the
      median follow-up time were 4.5 months, 4 months and 49% respectively. Of this
      cohort 39% were complete responders (CR) and 36% were long-term lymphoma-free
      survivors. Two patients relapsed from CR. Short course intensive chemotherapy
      (McMaster) was administered to 23 patients; 17 received less intensive
      conventional combination chemotherapy; and four received single-agent
      chemotherapy or no treatment. In the McMaster group, 38% (9/23) achieved CR with
      no relapses. Seven patients (30%) died of toxicity compared with one (6%) in the
      less intensively treated group. Of the stage I patients, 75% (6/8) achieved long
      term CR with half being treated conventionally. Conventional chemotherapy may be
      curative for early stage HIV-SNCL. In advanced disease, McMaster chemotherapy was
      found to be associated with substantial early mortality but was curative in a
      significant number of patients.

PMID- 14579242
TI  - 2003 as a vantage point for genetics past and genetics future.

PMID- 14579244
TI  - Anti-cancer selection as a source of developmental and evolutionary constraints.
AB  - Recently at least two papers have appeared that look at cancer from an
      evolutionary perspective. That cancer has a negative effect on fitness needs no
      argument. However, cancer origination is not an isolated process, but the
      potential for it is linked in diverse ways to other genetically determined
      developmental events, complicating the way selection acts on it, and through it
      on the evolution of development. The two papers take a totally different line.
      Kavanagh argues that anti-cancer selection has led to developmental constraints.
      Leroi et al. argue that cancer is a side-effect of recent evolutionary changes
      that usually will disappear over time through anti-cancer selection. Here we
      place the papers in a wider perspective, and in so doing discuss various
      alternative developmental links cancer may have together with their evolutionary
      implications.

PMID- 14579243
TI  - Alternative splicing and evolution.
AB  - Alternative splicing is a critical post-transcriptional event leading to an
      increase in the transcriptome diversity. Recent bioinformatics studies revealed a
      high frequency of alternative splicing. Although the extent of AS conservation
      among mammals is still being discussed, it has been argued that major forms of
      alternatively spliced transcripts are much better conserved than minor forms. It
      suggests that alternative splicing plays a major role in genome evolution
      allowing new exons to evolve with less constraint.

PMID- 14579245
TI  - Intercalary heterochromatin and genetic silencing.
AB  - We focus here on the intercalary heterochromatin (IH) of Drosophila melanogaster
      and, in particular, its molecular properties. In the polytene chromosomes of
      Drosophila, IH is represented by a reproducible set of dense bands scattered
      along the euchromatic arms. IH contains mainly unique DNA sequences, and shares
      certain features with other heterochromatin types such as pericentric, telomeric,
      and PEV-induced heterochromatin, the inactive mammalian X-chromosome and the
      heterochromatized male chromosome set in coccids. These features are
      transcriptional silencing, chromatin compactness, late DNA replication,
      underrreplication or elimination in somatic cells, and formation of the
      heterochromatin state in early embryogenesis. Post-translational modification of
      histones and the specific nonhistone protein complexes are shown to participate
      in the establishment and maintenance of silencing for all heterochromatin types.
      Many IH regions contain binding sites for HP1 and/or Pc-G proteins and all the
      regions are sites of heterochromatin-associated SuUR protein. Some IH regions are
      known to contain homeotic genes. Summarizing these data, we suggest that IH
      regions comprise stable inactivated genes, whose silencing is developmentally
      programmed.

PMID- 14579246
TI  - Growing and shaping the vascular tree: multiple roles for VEGF.
AB  - Vascular Endothelial Growth Factor (VEGF) is the most potent and ubiquitous
      vascular growth factor known to date. Yet, prior to its description as a secreted
      mitogen for endothelial cells, it was identified as a vascular permeability
      factor. These seemingly disparate avenues of discovery highlight VEGF's ability
      to control many distinct aspects of endothelial cell behaviour, including
      proliferation, migration, specialisation and survival. The versatility of VEGF as
      a patterning molecule is likely linked to its association with various signalling
      receptor complexes, but also its expression in several isoforms with a
      differential affinity for heparan sulfate proteoglycans in the extracellular
      matrix. In contrast to the absolute requirement for all known VEGF receptors, the
      presence of only a single VEGF isoform is sufficient for vascular development.
      However, the isoforms serve as exquisite tools for the fine patterning of growing
      vessel networks during embryogenesis and in postnatal life.

PMID- 14579247
TI  - Human severe combined immune deficiency and DNA repair.
AB  - Human severe combined immune deficiency (SCID) is the most serious inherited
      immunological deficit. Recent work has revealed defects in the predominant
      pathway for double-strand break repair called nonhomologous DNA end joining, or
      NHEJ. Progress in the biochemistry and genetics of NHEJ and of human SCID has
      proven to be synergistic between these two fields in a manner that covers the
      range from biochemical etiology to considerations about possible gene therapy for
      the B- SCID patients.

PMID- 14579248
TI  - DNMT cooperativity--the developing links between methylation, chromatin structure
      and cancer.
AB  - Controversy has reigned for some time over the biological connection between DNA
      methylation and cancer. For this reason, the methylation mechanism responsible
      for increased cancer risk has received greater attention in recent years. Tumor
      suppressor genes are often hypermethylated resulting in gene silencing. Although
      some have questioned this interpretation of the link between methylation and
      cancer, it appears that both hypermethylation and hypomethylation events can
      create epigenetic changes that can contribute to cancer development. Recent
      studies have shown that the methyltransferases DNMT1 and DNMT3b cooperatively
      maintain DNA methylation and gene silencing in human cancer cells. Disruption of
      the human DNMT3b only slightly reduces the overall global DNA methylation;
      however, demethylation was markedly potentiated when both DNMT1 and DNMT3b were
      simultaneously deleted. The results to these experiments provide compelling
      evidence towards a role for DNA methylation in cancer. This review discusses the
      current understanding of cancer-epigenetic information and highlights recent
      studies that connect the methylation machinery and chromatin remodelling with
      cancer susceptibility.

PMID- 14579249
TI  - Chronic activation of ERK and neurodegenerative diseases.
AB  - The extracellular-signal regulated kinases 1/2 (ERK or ERKs) are involved in the
      regulation of important neuronal functions, including neuronal plasticity in
      normal and pathological conditions. We present findings that support the notion
      that the kinetics and localization of ERK are intrinsically linked, in that the
      duration of ERK activation dictates its subcellular compartmentalization and/or
      trafficking. The latter, in turn, dictates whether ERK-expressing cells would
      enter a program of cell death, survival or differentiation. We summarize
      experimental data showing that chronic activation of ERK plays a role in the
      mechanisms that trigger neurodegeneration. We also discuss how MKPs, members of
      the subclass of dual specificity phosphatases, might be the link between ERK
      kinetics and its subcellular localization.

PMID- 14579250
TI  - TRAF6, a molecular bridge spanning adaptive immunity, innate immunity and
      osteoimmunology.
AB  - Tumor necrosis factor (TNF) receptor associated factor 6 (TRAF6) is a crucial
      signaling molecule regulating a diverse array of physiological processes,
      including adaptive immunity, innate immunity, bone metabolism and the development
      of several tissues including lymph nodes, mammary glands, skin and the central
      nervous system. It is a member of a group of six closely related TRAF proteins,
      which serve as adapter molecules, coupling the TNF receptor (TNFR) superfamily to
      intracellular signaling events. Among the TRAF proteins, TRAF6 is unique in that,
      in addition to mediating TNFR family signaling, it is also essential for
      signaling downstream of an unrelated family of receptors, the interleukin-1 (IL
      1) receptor/Toll-like receptor (IL-1R/TLR) superfamily. Gene targeting
      experiments have identified several indispensable physiological functions of
      TRAF6, and structural and biochemical studies have revealed the potential
      mechanisms of its action. By virtue of its many signaling roles, TRAF6 represents
      an important target in the regulation of many disease processes, including
      immunity, inflammation and osteoporosis.

PMID- 14579251
TI  - PAD, a growing family of citrullinating enzymes: genes, features and involvement
      in disease.
AB  - Peptidylarginine deiminase (PAD, EC 3.5.3.15) enzymes catalyze the conversion of
      protein-bound arginine to citrulline. This post-translational modification may
      have a big impact on the structure and function of the target protein. In this
      review, we will discuss the effects of citrullination and its involvement in
      several human diseases, including rheumatoid arthritis and multiple sclerosis. So
      far, four isotypes of PAD have been described in mammals. We describe the
      existence of PAD in non-mammalian vertebrates and the existence of a fifth
      mammalian PAD. In addition, tissue-specific expression, genomic organization and
      evolutionary conservation of the different PAD isotypes will be discussed in
      detail. This article contains supplementary material which may be viewed at the
      BioEssays website at http://www.interscience.wiley.com/jpages/0265
      9247/suppmat/2003/25/v25.1106.html.

PMID- 14579252
TI  - Pathogenic archaea: do they exist?
AB  - Archaea are microorganisms that are distinct from bacteria and eukaryotes. They
      are prevalent in extreme environments, and yet found in most ecosystems. They are
      a natural component of the microbiota of most, if not all, humans and other
      animals. Despite their ubiquity and close association with humans, animals and
      plants, no pathogenic archaea have been identified. Because no archaeal pathogens
      have yet been identified, there is a general assumption that archaeal pathogens
      do not exist. This review examines whether this is a good assumption by
      investigating the potential for archaea to be or become pathogens. This is
      achieved by addressing: the diversity of archaea versus known pathogens,
      opportunities for archaea to demonstrate pathogenicity and be detected as
      pathogens, reports linking archaea with disease, and immune responses to archaea.
      In addition, molecular and genomic data are examined for the presence of systems
      utilised in pathogenesis. The view of this report is that, although archaea can
      presently be described as non-pathogenic, they have the potential to be
      (discovered as) pathogens. The present optimistic view that there are no archaeal
      pathogens is tainted by a severe lack of relevant knowledge, which may have
      important consequences in the future.

PMID- 14579253
TI  - Small GTPases and the evolution of the eukaryotic cell.
AB  - The origin of eukaryotes is one of the major challenges of evolutionary cell
      biology. Other than the endosymbiotic origin of mitochondria and chloroplasts,
      the steps leading to eukaryotic endomembranes and endoskeleton are poorly
      understood. Ras-family small GTPases are key regulators of cytoskeleton dynamics,
      vesicular trafficking and nuclear function. They are specific for eukaryotes and
      their expansion probably traces the evolution of core eukaryote features. The
      phylogeny of small GTPases suggests that the first endomembranes to evolve during
      eukaryote evolution had secretory, and not phagocytic, function. Based on the
      reconstruction of putative roles for ancestral small GTPases, a hypothetical
      scenario on the origins of the first endomembranes, the nucleus, and phagocytosis
      is presented.

PMID- 14579254
TI  - Thinking both inside and outside the box on measurement articles.

PMID- 14579255
TI  - Factors of positive appraisal of care among Japanese family caregivers of older
      adults.
AB  - The purpose of this study was to examine factors of positive appraisal of care
      among Japanese family caregivers of older adults. The Positive Appraisal of Care
      (PAC) scale used in this study is a multidimensional Japanese measure and has
      four domains: relationship satisfaction, consequential gain, role confidence, and
      normative fulfillment. Three hundred and thirty-seven caregivers participated in
      this survey. Multiple regression analyses revealed that social support and
      caregiver belief in caregiving had a consistent impact on all domains of the PAC,
      whereas the impact of caregiver and care recipient characteristics varied among
      the domains. For example, caregiver age had a significant impact on role
      confidence and normative fulfillment but not on relationship satisfaction and
      consequential gain. The differential impact of caregiver and care recipient
      characteristics on the domains of the PAC underlines the usefulness of a
      multidimensional measurement.

PMID- 14579256
TI  - Work narratives: gender and race in professional personhood.
AB  - An ethnographic study was conducted to explore how nurses construe and understand
      their professional culture and their professional personhood. The sample was 36
      nurses ranging in age from 26 to 63 (12 African American women, 11 White women,
      13 men 12 White and 1 Caribbean Islander). Data were gathered through participant
      observation, audiotaped individual conversations, a process of seven consecutive
      group sessions, and short narratives written by the nurses in group sessions. The
      data were analyzed: (a) by a coding system that focused on the formal and
      informal roles, rules, and relationships in work and school settings; and (b) by
      examining the changes in participants' narratives about their professional
      identity during the process of the group meetings. All the nurses in the sample
      had been profoundly affected by the socially accepted "feminine" images of
      nursing. The findings also revealed racial issues in the nursing profession. The
      implications of this study point to the need for new models of nursing education
      and nursing leadership to overcome old images and to make nursing attractive to
      those from diverse backgrounds.

PMID- 14579257
TI  - Alzheimer's disease caregiving information and skills. Part I: care recipient
      issues and concerns.
AB  - Increasing attention has been given to testing clinical trials with family
      caregivers of the elderly. More recent intervention studies indicated that
      caregiver skill-building interventions may be more effective than
      information/support interventions. Researchers have given considerable attention
      to the content and support needed by family caregivers, but we know less about
      how this content and support translates into caregiver skills. This is the first
      in a series of three articles on a study in which qualitative methods were used
      to analyze summaries from the group component of a larger caregiver clinical
      trial. In this article we identify content and skills that dementia family
      caregivers need in addressing three major care recipient issues and concerns: (a)
      difficult behaviors and emotional responses, (b) personal and instrumental
      activities of daily living, and (c) cognitive decline.

PMID- 14579258
TI  - Validation of measures of middle schoolers' self-efficacy for physical and
      emotional health, and academic tasks.
AB  - The development and psychometric study of a measure of middle schoolers'
      perceptions of self-efficacy for physical, emotional, and academic behaviors
      appropriate to their age and developmental tasks are described. The validation of
      the Middle School Self-Efficacy Questionnaire (MISSE) included the adaptation of
      existing items and the generation of new ones. Items were subjected to judges'
      review by two expert panels and were tested with a large, geographically diverse
      sample of youngsters aged 11-14. Statistical analyses included factor analysis,
      internal consistency estimations, t tests, and analyses of variance for
      hypothesis testing related to construct validity. Results showed support for the
      expected factors and provided evidence of the validity of the MISSE.

PMID- 14579259
TI  - Smoking and adolescence: narratives of identity.
AB  - The purpose of this study was to understand the identities that youth hold in
      relation to smoking, as revealed in narrative accounts of their smoking
      experiences. The analysis was a narrative inquiry, a qualitative approach based
      on the propensity of people to narrate or tell stories about the experiences in
      their daily lives. A purposeful sample of 35 youths ages 14-18 years with a
      variety of smoking histories (all had tried smoking) participated in in-depth
      interviews. A detailed analysis of the transcripts revealed the key identities
      communicated by the youths including the confident nonsmoker, the vulnerable
      nonsmoker, the ardent nonsmoker, the accepting nonsmoker, the in-control smoker,
      the confirmed smoker, and the contrite smoker. Tobacco control interventions for
      youth must be designed to respond to and incorporate multiple smoking identities.

PMID- 14579260
TI  - Adverse events in acute care: an integrative literature review.
AB  - An integrative literature review was conducted to investigate studies on adverse
      events reported in medical, health services, and nursing literature. The review
      was guided by the method proposed by Jackson (1980) and Ganong (1987). Three
      questions shaped the review: (a) What terms are used to denote adverse events?
      (b) What purposes drive adverse events research? and (c) What data sources are
      used to study adverse events? Adverse events was the dominant term, the study of
      adverse events as an outcome variable was the prevailing research purpose, and
      monitoring or screening the patient clinical record and self-reported incidents
      by health care professionals were the main data sources. Future research is
      recommended to conceptualize and study adverse events.

PMID- 14579261
TI  - A new methodological approach in nursing research: an actor, partner, and
      interaction effect model for family outcomes.
AB  - Methodological and statistical challenges have been identified in family research
      when the parental dyad is under study. The purposes of this article are to review
      the literature on methodological and statistical procedures in research on
      families, and to introduce an analysis technique that is new to the nursing
      literature, the actor-partner interdependence model (APIM). The use and
      interpretation of the APIM method is illustrated through an example of families
      of young children with asthma. In the APIM an actor effect is the impact a person
      has on his or her own outcome, whereas a partner effect is the impact a member of
      a dyad has on his or her partner's outcome. The main findings from the data
      example indicate that family adaptation is influenced by the actor effect of
      resiliency factors (sense of coherence and family hardiness), the partner effect
      of caregiving demands, as well as by both the actor and partner effects of family
      demands. The APIM method gives new insight into how parental data can be analyzed
      by taking both the individual and the partner contribution into account when
      studying family phenomena. Knowing how outcomes may be influenced not only by
      individuals (via an actor effect) but also by their partners (through a partner
      effect) enriches our understanding of how families function.

PMID- 14579263
TI  - Control of inflammatory diseases by pathogens: lipids and the immune system.
AB  - Inflammatory diseases such as asthma and diabetes are rising in industrialized
      countries and the modern lifestyle that is associated with lower exposure to
      microbes has been held responsible for the increasing prevalence of these
      diseases. Several studies have shown an inverse association between pathogen
      exposure and allergy or autoimmunity. The mechanisms behind such protective
      effects have been investigated at the epidemiological, cellular and molecular
      level and have provided data on the ability of lipids either derived directly
      from pathogens or up-regulated as a result of an infection to down-regulate
      immune responses and thereby control inflammatory diseases. In this mini-review,
      recent findings and new concepts relating to the immunosuppressive effects of
      endogenous lipids and those encountered upon exposure to bacteria, protozoa and
      particularly helminths are discussed. The overview focuses on the modulation of
      interactions between the antigen-presenting compartment and T cells to start an
      anti-inflammatory "program" with potential to regulate disease processes.

PMID- 14579264
TI  - Identification of a CTL-directed epitope encoded by an intron of the putative
      tumor suppressor gene Testin of the common fragile site 7G region: a peptide
      vaccine candidate for HLA-B52+ and HLA-62+ cancer patients.
AB  - Although cytotoxic T lymphocyte (CTL)-directed epitopes binding to human
      histocompatibility leukocyte antigen (HLA)-A molecules have been well
      characterized, those binding to HLA-B molecules have not, largely due to their
      large diversity. In this study we report a unique cancer antigen gene,
      tentatively named Testin-related gene (TRG), which encodes CTL-directed epitopes
      on the HLA-B52 molecules most frequently expressed in Asians. TRG is located in
      an intron of the putative tumor suppressor gene Testin in the common fragile site
      7G region at 7q31.2. TRG mRNA was expressed in the majority of cancer cells and
      cancer tissue tested, whereas it was scarcely expressed in the majority of normal
      tissues, and only low-level expression of TRG was detected in the heart, liver,
      and pancreas. One TRG peptide had the ability to induce HLA-B52-restricted CTL
      cytotoxic to TRG+ tumor cells in peripheral blood mononuclear cells (PBMC) of
      epithelial cancer patients. This peptide also induced HLA-B62-restricted and
      tumor-reactive CTL in PBMC of cancer patients. Therefore, this TRG-derived
      peptide might be appropriate for use in peptide-based immunotherapy for
      relatively large numbers of cancer patients throughout the world, given that 34%
      of Japanese, 27% of Chinese, and 13% of Caucasians express either HLA-B52 or HLA
      B62 molecules

PMID- 14579265
TI  - Essential role for TLR4 and MyD88 in the development of chronic intestinal
      nematode infection.
AB  - Expulsion of the gastrointestinal nematode Trichuris muris is mediated by a T
      helper 2 type response involving IL-4 and IL-13. Here we show that Th1 response
      associated susceptibility is dependent on activation signals mediated by MyD88
      and Toll-like receptor 4 (TLR4). TLR4- and MyD88-deficient mice are highly
      resistant to chronic T. muris infection and develop strong antigen-specific Th2
      responses in mucosa-associated lymphoid tissues. Hence, TLR4 and MyD88 are
      involved not only in the development of pro-inflammatory responses against
      bacterial pathogens but are also crucially involved in responses against
      multicellular organisms such as helminths. These results provide the first
      demonstration of the critical role of TLR4 and MyD88 in bridging the innate and
      acquired immune response during gastrointestinal nematode infection.

PMID- 14579266
TI  - Human dendritic cells respond to Porphyromonas gingivalis LPS by promoting a Th2
      effector response in vitro.
AB  - Understanding how mucosal pathogens modulate the immune response may facilitate
      the development of vaccines for disparate human diseases. In the present study,
      human monocyte-derived DC (MDDC)were pulsed with LPS of the oral pathogen
      Porphyromonas gingivalis and Escherichia coli 25922 and analyzed for: (i)
      production of Th-biasing/inflammatory cytokines; (ii) maturation/costimulatory
      molecules; and (iii) induction of allogeneic CD4+ and naive CD45RA+ T cell
      proliferation and release of Th1 or Th2 cytokines. We show that E. coli LPS
      pulsed MDDC released Th1-biasing cytokines - consisting of high levels of IL-12
      p70, IFN-gamma-inducible protein 10 (IP-10) - but also TNF-alpha, IL-10, IL-6 and
      IL-1beta. In contrast, no IL-12 p70 or IP-10, and lower levels of TNF-alpha and
      IL-10 were induced by P. gingivalis LPS. These differences were sustained at LPS
      doses that yielded nearly equivalent maturation of MDDC; moreover the T cell
      response was consistent: E. coli LPS-pulsed MDDC induced higher T cell
      proliferation, and T cells released more IFN-gamma and IL-2, but less IL-5 than T
      cells co-cultured with P. gingivalis LPS pulsed-MDDC. IL-13 was secreted by naive
      CD45RA+CD45RO-CD4+ T cells in response to P. gingivalisLPS-pulsed MDDC. These
      results suggest that human MDDC can be polarized by LPS from the mucosal pathogen
      P. gingivalis to induce a Th2 effector response in vitro.

PMID- 14579268
TI  - The brain as an immune privileged site: dendritic cells of the central nervous
      system inhibit T cell activation.
AB  - Dendritic cells (DC) are unique in their ability to prime naive T cells and
      initiate adaptive immunity. In recent years, DC were identified in the inflamed
      central nervous system (CNS), but their role in the initiation or regulation of
      the tissue specific immune response is unknown. As shown here, DC isolated from
      mice with experimental autoimmune encephalomyelitis (EAE) exhibit a maturational
      phenotype similar to immature bone marrow-derived DC or splenic DC as
      characterized by intermediate surface MHC class II and low expression of the
      costimulatory molecule CD80. However, they are unable to prime naive T cells.
      Moreover, they inhibit T cell proliferation stimulated by mature bone marrow
      derived DC. TGFbeta, IL-10 and TRAIL were found to significantly contribute to
      the CNS-DC-mediated inhibition of allo-T cell proliferation. Thus CNS-DC may be
      the key responsibles for maintaining immune privilege within the inflamed CNS.

PMID- 14579267
TI  - The Toll-like receptor 7 (TLR7)-specific stimulus loxoribine uncovers a strong
      relationship within the TLR7, 8 and 9 subfamily.
AB  - Loxoribine (7-allyl-7,8-dihydro-8-oxo-guanosine) acts as synthetic adjuvant in
      anti-tumor responses. Here we first demonstrate that loxoribine activates cells
      of the innate immune system selectively via the Toll-like receptor (TLR) 7/MyD88
      dependent signaling pathway. TLR7- and MyD88-deficient immune cells fail to
      proliferate or produce cytokines in response to loxoribine, and genetic
      complementation of TLR7-deficient cells with murine or human TLR7 confers
      responsiveness. Subsequently we show that cellular activation by loxoribine and
      resiquimod (R-848), a stimulus for TLR7 and TLR8, depends on acidification and
      maturation of endosomes and targets MyD88 to vesicular structures with lysosomal
      characteristics. This mode of TLR7 and TLR8 action resembles CpG-DNA-driven TLR9
      activation. We thus conclude that TLR7, 8 and 9 form a functional subgroup within
      the TLR family that recognizes pathogen-associated molecular patterns in
      endosomal/lysosomal compartments.

PMID- 14579269
TI  - In vivo expression of recombinant pregnancy-specific glycoprotein 1a induces
      alternative activation of monocytes and enhances Th2-type immune response.
AB  - It has been proposed that pregnancy-specific factors could be responsible for
      shift the balance of cytokine profiles during maternal immune response from Th1
      type reactivity into a "less-damaging" Th2-type reactivity. In the present work,
      we investigated the in vivo function of human pregnancy-specific glycoprotein
      (PSG)1a, the major variant of PSG polypeptides released into the circulation
      during pregnancy, on the modulation of the innate and adaptive immune response.
      For this, BALB/c mice were injected with a vaccinia virus-based vector harboring
      the human PSG1a cDNA (Vac-PSG1a) 4 days before immunization with ovalbumin (OVA)
      in complete Freund's adjuvant, and the early specific T cell response against OVA
      was evaluated 8 days post-immunization. We also studied the activation status of
      spleen and peritoneal monocytes/macrophages (Mo) populations from Vac-PSG1a
      treated mice, and explored whether PSG1a-targeted Mo could affect the Th-type
      commitment by investigating their impact on the differentiation of naive T cells.
      Our data show that the treatment with Vac-PSG1a is able to induce a state of
      alternative activation on Mo. Furthermore, the generation of the immune response
      in the context of these alternatively activated antigen-presenting cells may
      shift T cell differentiation to Th2-type immunity which is more compatible with a
      successful pregnancy.

PMID- 14579270
TI  - Two highly divergent ancient allelic lineages of the transporter associated with
      antigen processing (TAP) gene in Xenopus: further evidence for co-evolution among
      MHC class I region genes.
AB  - In the frog Xenopus, MHC class I antigen presentation and processing genes (the
      immunoproteasome LMP2 and LMP7 and the transporter TAP1 and TAP2) seem to be
      closely linked in a primordial organization. Two distinct lineages of class Ia
      and LMP7 loci were previously identified, thus strongly suggesting co-evolution
      among 'class I region' genes. We now show that the Xenopus MHC 'class I region'
      lies between class II and class III genes and we have isolated two distinct
      alleles at both the TAP1 and TAP2 loci. The alleles at each locus are remarkably
      divergent from each other and phylogenetic tree analysis revealed in both cases
      that they diverged from each other 60-100 million years ago (MYA). For lineage
      frequency and linkage analysis, 25 wild-caught X. laevis and 16 X. tropicalis
      were examined. The two lineages were present in different frequencies for X.
      laevis and X. tropicalis. Nevertheless, in all cases, the LMP7, TAP1, and TAP2
      lineages were found in a set comprising one of the two lineages. Furthermore,
      like the LMP7 lineages, the TAP lineages were detected in most Xenopus species
      that diverged from a common ancestor 80-100 MYA, suggesting that the 'class I
      region' biallelic lineages are under balancing selection.

PMID- 14579271
TI  - Post-translational and cell type-specific regulation of CXCR4 expression by
      cytokines.
AB  - We have investigated the regulation and function of the chemokine receptor CXCR4
      on neutrophils. CXCR4 is hardly detectable on neutrophils in the peripheral
      blood. However, overnight culture strongly up-regulates CXCR4 expression on the
      cell surface. The functional activity of CXCR4 on cultured neutrophils was
      confirmed by stromal cell-derived factor (SDF)-induced migration and up
      regulation of the integrins CD11b and CD11c. CXCR4 surface expression on
      neutrophils but not on lymphocytes and monocytes is rapidly down-regulated after
      stimulation with TNF-alpha and IFN-gamma, resulting in significantly decreased
      SDF-induced functional responses of neutrophils. In contrast to surface
      expression, CXCR4 mRNA expression was several-fold increased in cytokine
      stimulated neutrophils, suggesting a post-translational regulation. By confocal
      microscopy we demonstrate that CXCR4 is internalized after stimulation with TNF
      alpha and IFN-gamma. Tauhe down-modulation of CXCR4 surface expression in
      response to TNF-alpha and IFN-gamma was fully reversible after cytokine removal.
      Further, CXCR4 down-modulation could be completely blocked by hypertonic sucrose
      and significantly reduced by chlorpromazine indicating the involvement of
      clathrin-coated pits. Internalization of CXCR4 by cytokines in a cell type
      specific manner is a novel and functionally important mechanism of chemokine
      receptor regulation.

PMID- 14579272
TI  - p38 MAPK is a critical regulator of the constitutive and the beta4 integrin
      regulated expression of IL-6 in human normal thymic epithelial cells.
AB  - Cytokines and adhesion receptors are key mediators in the dialog occurring
      between thymic epithelial cells (TEC) and thymocytes and regulating T cell
      maturation and epithelial embryonic differentiation. Among cytokines, IL-6 can be
      critical in the thymus, fostering proliferation, differentiation and/or survival
      of both TEC and thymocytes. We have previously reported in human normal TEC that
      clustering of the laminin receptor alpha6beta4 integrin induced by thymocyte
      contact or monoclonal antibody-mediated cross-linking regulates IL-6 gene
      expression via activation of NF-kappaB and NF-IL6 transactivators. Here we show
      that alpha6beta4 integrin activates p38 mitogen-activated protein kinase (MAPK)
      and that p38 is essential for IL-6 gene expression. In fact, beta4 cross-linking
      activated p38 and extracellular signal-regulated kinase (ERK) MAPK, Rac1, p21
      activated protein kinase 1 (PAK1) and MAPK kinases (MKK) 3/MKK6. However,
      pharmacological blockade of p38 or ERK demonstrated that p38 inhibition abrogated
      both basal and beta4 integrin-induced production of IL-6 preventing NF-kappaB and
      NF-IL6 activation, whereas ERK inhibition reduced IL-6 production, hampering only
      NF-kappaB activation. Overall, our results indicate that p38 MAPK and alpha6beta4
      integrin, expressed by TEC throughout their life, are critical regulators of the
      intrathymic availability of a cytokine controlling fate and functions of cells
      governing development and maintenance of thymic architecture and immune
      responses.

PMID- 14579273
TI  - IFN-gamma production in human NK cells through the engagement of CD8 by soluble
      or surface HLA class I molecules.
AB  - The engagement of CD8 on NK cell surface by either surface or soluble HLA class I
      (sHLA-I) molecules induces synthesis and secretion of IFN-gamma. HLA-I-mediated
      effects were inhibited by the covering of CD8 with specific anti-CD8 monoclonal
      antibodies, indicating a direct interaction of HLA-I and CD8. That CD8 ligation
      induces IFN-gamma production was further supported by the finding that cross
      linking of CD8 led to release of IFN-gamma at similar levels to those obtained
      with HLA-I. The sHLA-I-induced IFN-gamma production via CD8 was strongly down
      regulated by the engagement of the inhibitory isoforms of either CD94/NKG2
      complex by sHLA-I-non-(A,B,C,G) (putative sHLA-E) or CD158b by sHLA-I-Cw3 allele.
      Ligation of CD8 did not elicit, different from other activating NK cell surface
      molecules such as CD16 or CD69, triggering of NK cell-mediated cytolysis.
      Cyclosporin A, but not concanamycin A, an H+-ATPase vacuolar inhibitor which
      affects perforin and granzyme release, strongly reduced the sHLA-I-mediated CD8
      dependent IFN-gamma production but did not affect cytolytic activity of NK cells,
      suggesting that different biochemical pathways are involved. Altogether, these
      findings indicate that CD8 engagement by sHLA-I activates a cyclosporin A
      dependent pathway leading to production and secretion of IFN-gamma which may play
      a role in the regulation of innate immune responses in humans.

PMID- 14579274
TI  - Structural and kinetic basis for low affinity cross-reactivity in T cell
      allorecognition.
AB  - The alloreactive BM3.3TCR interacts with high affinity with H-2Kb loaded with the
      endogenous peptide pBM1 (INFDFNTI), and shows low affinity cross-reactivity for H
      2Kb loaded with a viral peptide VSV8 (RGYVYQGL), CTL activity requiring 10(3)
      fold higher peptide concentration and being highly sensitive to inhibition by
      anti-CD8 monoclonal antibody. VSV8 peptides substituted with pBM1/TCR contact
      residues (N6 and T7) retained low affinity characteristics and among pBM1
      peptides substituted with residues Q6 and/or G7 present in VSV8, only pBM1(G7)
      was recognized, albeit with characteristics akin to those of VSV8. Despite the
      difference in KD values and the faster dissociation rate of multimeric VSV8/H-2Kb
      as compared to pBM1/H-2Kb complexes, similar TCR occupancy could be achieved with
      both multimers either at 4 or 37 degrees C. Only TCR engagement with pBM1/H-2Kb,
      however, resulted in early (Ca2+ flux) and late (CD69 expression) activation
      events in naive BM3.3TCR CD8 T cells. CD8 coreceptor, essential for binding of
      the weak agonists, was dispensable for binding of pBM1/H-2Kb multimers and their
      induction of signaling in naive T cells. Hence, high number of TCR and coreceptor
      engagement by weak agonists fail to substitute for strong agonist TCR engagement
      that can be coreceptor-independent and involve a limited number of TCR.

PMID- 14579275
TI  - Pituitary adenylate cyclase-activating polypeptide inhibits cutaneous immune
      function.
AB  - Epidermal nerves are closely associated with Langerhans cells (LC) and may be
      able to release factors, such as calcitonin gene-related peptide and epinephrine,
      that affect LC function. LC and the LC-like cell line XS106 express mRNA for the
      pituitary adenylate cyclase-activating polypeptide (PACAP) receptors VPAC1 and
      VPAC2. We examined whether PACAP regulates cutaneous immunity. Intradermal
      administration of PACAP prior to application of a contact sensitizer at the
      injected site inhibited the induction of contact hypersensitivity. Pretreatment
      of murine epidermal cells enriched for LC content (approximately 12% LC) with
      PACAP inhibited their ability to elicit delayed-type hypersensitivity in
      previously immunized mice. In vitro, PACAP suppressed the ability of both murine
      epidermal cells and highly purified LC (approximately 95%) to present antigen to
      a T cell clone and hybridoma. Furthermore, in LC and the XS106 cell line, PACAP
      inhibited the LPS/GM-CSF-induced stimulation of IL-1beta secretion and augmented
      IL-10 production. PACAP also down-regulated CD86 expression in LPS/GM-CSF
      stimulated XS106 cells. The immunosuppressive effects of PACAP may be due to
      modulation of cytokine production and CD86 expression.

PMID- 14579276
TI  - Intrapulmonary targeting of RANTES/CCL5-responsive cells prevents chronic fungal
      asthma.
AB  - Regulated upon activation in normal T cells, expressed, and secreted
      (RANTES)/CCL5 is abundantly expressed during atopic asthma, suggesting that it is
      an important mediator of this disease. The contribution of intrapulmonary
      RANTES/CCL5-sensitive cells during Aspergillus fumigatus-induced airway disease
      in mice was assessed in this study. The intranasal delivery of a chimeric protein
      comprised of RANTES/CCL5 and a truncated version of Pseudomonas exotoxin A
      (RANTES-PE38) significantly attenuated serum IgE, peribronchial eosinophilia, and
      airway hyperreactivity when it was administered from day 0 to 15 after
      intratracheal conidia challenge in A. fumigatus-sensitized mice but had little
      effect when delivered from day 15 to 30 after conidia challenge. Intranasal
      RANTES-PE38 treatment enhanced macrophage recruitment and accelerated fungal
      clearance in the lungs of RANTES-PE38-treated mice. These data reveal a major
      role for RANTES/CCL5 and its receptors in the development of fungal asthma yet
      reveal only a modest role in the chronic remodeling of the allergic airway in
      this disease.

PMID- 14579277
TI  - Macrophage colony-stimulating factor-dependent macrophage proliferation is
      mediated through a calcineurin-independent but immunophilin-dependent mechanism
      that mediates the activation of external regulated kinases.
AB  - Calcineurin is constitutively expressed in bone marrow-derived macrophages.
      However, macrophage response to macrophage colony-stimulating factor (M-CSF) was
      not impaired by the use of either calcineurin inhibitors (W-13, chlorpromazine
      and trifluoperazine), calcium chelators (BAPTA-AM) or Ca2+ channel antagonists
      (verapamil, nifedipine and diltiazem). Inhibition of calcineurin expression by
      inhibitory antisense RNA treatment did not result in an inhibition of M-CSF
      dependent proliferation. Only very high doses of cyclosporin A and FK506
      inhibited macrophage proliferation induced by growth factors, such as M-CSF,
      granulocyte-macrophage (GM)-CSF or IL-3. This inhibitory action is mediated by
      the peptidylprolyl isomerase activity of the immunophilins, as demonstrated bythe
      use of specific inhibitors (rapamycin and sanglifehrin A). These isomerase
      inhibitors exerted a negative effect on a key element involved in macrophage
      proliferation, namely the M-CSF-dependent activation of the extracellular signal
      regulated kinases (ERK). In summary, the data presented here provide new insights
      in the mechanism of macrophage proliferation, which may have relevant
      consequences. First, we showed that in M-CSF-dependent proliferation calcineurin
      is not involved, and second, that immunophilins play a key role and their
      activation blocks ERK activation.

PMID- 14579278
TI  - Antibody-mediated delivery of antigen to chemokine receptors on antigen
      presenting cells results in enhanced CD4+ T cell responses.
AB  - Here, we have investigated if targeting of T cell epitopes to chemokine receptors
      results in improved CD4+ T cell responses. Mouse monoclonal antibodies (mAb) with
      kappaL chains were targeted to various chemokine receptors expressed on human
      monocytes or immature dendritic cells (DC), and proliferation of cloned human,
      DR4-restricted CD4+ T cells specific for mouse Ckappa(40-48) was measured. When
      using monocytes as antigen-presenting cells, mAb specific for CCR1, CCR2, CCR5,
      and CXCR4 were 100-10,000-fold more efficient at inducing T cell proliferation
      when compared to isotype-matched control mAb on a per molecule basis. Targeting
      of immature DC was less effective and was only seen with anti-CCR1 and anti-CXCR4
      mAb. Anti-chemokine receptors mAb required to be processed by the conventional
      endosomal MHC class II presentation pathway. The mAb did not induce signaling
      through the chemokine receptors as they failed to induce mobilization of
      cytosolic Ca2+ and actin polymerization. They also failed to induce APC
      maturation. The results strongly suggest that chemokine receptors channel antigen
      into the endocytic pathway for presentation on MHC class II molecules. Targeting
      T cell epitopes to chemokine receptors by recombinant antibody should be a useful
      vaccine strategy for the induction of strong CD4+ T cell responses.

PMID- 14579279
TI  - T cell stimulation in the absence of exogenous antigen: a T cell signal is
      induced by both MHC-dependent and -independent mechanisms.
AB  - Mature T cells residing in peripheral lymphoid organs have frequent contact with
      antigen presenting cells (APC). Such contact may be required for T cell survival,
      but the degree to which signals in mature T cells are induced by TCR recognition
      of self peptide/MHC complexes is unclear. We have used induction of the early
      growth response gene 1 (Egr1) as an indicator of signal transduction in 3.L2 (I
      Ek-restricted) T cells interacting with APC in the absence of exogenous antigen.
      The data show that Egr1 can be induced in 3.L2 T cells by TCR recognition of self
      peptides presented by I-Ek. However, a more transient induction of Egr1 can be
      induced in 3.L2 T cells interacting with dendritic cells derived from class
      II/beta2m double-deficient mice. Egr1 induction after T cell-APC contact was also
      observed in a freshly isolated polyclonal CD4 T cell population. The data suggest
      that self peptide/MHC recognition by the TCR induces a signal in T cells and that
      dendritic cells can also induce a more transient T cell signal by an MHC
      independent mechanism.

PMID- 14579280
TI  - Endothelial expression of PD-L1 and PD-L2 down-regulates CD8+ T cell activation
      and cytolysis.
AB  - Interactions between CD8+ T cells and endothelial cells are important in both
      protective and pathologic immune responses. Endothelial cells regulate the
      recruitment of CD8+ T cells into tissues, and the activation of CD8+ T cells by
      antigen presentation and costimulatory signals. PD-L1 and PD-L2 are recently
      described B7-family molecules which bind to PD-1 on activated lymphocytes and
      down-regulate T cell activation. We found that PD-L1 is expressed on interferon
      gamma stimulated cultured human and mouse endothelial cells, while PD-L2 was
      found on stimulated human but not mouse endothelial cells. Expression was further
      up-regulated by TNF-alpha. Antibody blockade of endothelial cell PD-L1 and PD-L2
      enhanced endothelial cell costimulation of PHA-activated human CD8+ T cells.
      Antibody blockade of mouse endothelial cell PD-L1 enhanced both IFN-gamma
      secretion and cytolytic activity of CD8+ T cells in response to endothelial cell
      antigen presentation. These results show that IFN-gamma activated endothelial
      cells can inhibit T cell activation via expression of the immunoinhibitory PD-L1
      and PD-L2 molecules. Endothelial expression of PD-ligands would allow activation
      and extravasation of T cells without excessive vessel damage. Our findings
      highlight a potentially important pathway by which endothelial cells down
      regulate CD8+ T cell-mediated immune responses.

PMID- 14579281
TI  - Endothelial cell cytoprotection induced in vitro by allo- or xenoreactive
      antibodies is mediated by signaling through adenosine A2 receptors.
AB  - Endothelial cell (EC) expression of proteins such as hemoxygenase-1 or Bcl-xL is
      associated with enhanced survival of vascularized allo- or xenografts. These
      grafts are resistant to humoral rejection, a phenomenon called accommodation. In
      vitro, low concentrations of allo- and xenoreactive antibody (XNA) induce a
      cytoprotective phenotype in EC similar to that seen in accommodated grafts. In
      this study we examine whether adenosine plays a role in antibody-induced
      cytoprotection. Porcine EC were incubated with human anti-pig XNA or specific
      alloantibody. EC expressed Bcl-xL and were protected from TNF-mediated apoptosis.
      Bcl-xL expression was inhibited by an adenosine A2 receptor antagonist. Human
      anti-pig XNA were shown to bind and induce cyclic adenosine 3',5'-monophosphate
      (cAMP) generation through these receptors. This activity was abolished by
      depletion of anti-galalpha(1-3)gal-specific XNA. In contrast, alloantibody caused
      adenosine production. Protection from TNF-mediated apoptosis was also mediated
      through A2 receptor but involved additional non-cAMP-dependent signaling. This
      study indicates a molecular mechanism common to both antibody-mediated
      cytoprotection and ischemic preconditioning and suggests a potential therapeutic
      avenue based on adenosine for improving the outcome of transplanted grafts in
      those patients with pre-existing anti-graft antibody.

PMID- 14579282
TI  - CD30 ligation differentially affects CXCR4-dependent HIV-1 replication and
      soluble CD30 secretion in non-Hodgkin cell lines and in gamma delta T
      lymphocytes.
AB  - We studied whether signaling through CD30, a member of the TNF receptor family,
      affected acute infection with HIV-1, encompassing its entire replicative cycle.
      Several non-Hodgkin cell lines, targets of CXCR4-dependent (X4) HIV-1 infection,
      were positive for CD30 expression. CD30 ligation induced up-regulation of viral
      replication only in certain CD30+ cell lines. Enhancement of X4 virus replication
      by CD30 engagement inversely correlated with both CD30 surface density and
      constitutive NF-kappaB activation. Conversely, expression of CD30, but not of
      other members of the TNF receptor family, was proportional to constitutive NF
      kappaB binding. Concomitantly, secretion of soluble (s) CD30 increased in all
      cell lines by CD30 ligation. sCD30 release was enhanced by engagement of CD30
      alone and, to a greater extent, by co-engagement of CD3 also in primary gamma
      delta T lymphocytes, along with complementary modulations of their surface CD30
      expression. sCD30-containing supernatant specifically inhibited HIV-1 expression
      induced by CD30 engagement in chronically infected ACH-2 T cells; thus sCD30 may
      act as a negative feed-back molecule. In conclusion, we have delineated novel
      features of CD30 biology and underline the peculiar link of CD30 expression to
      constitutive NF-kappaB activation which is pivotal to both HIV replication and
      cell survival.

PMID- 14579283
TI  - Microbial Toll-like receptor ligands differentially regulate CXCL10/IP-10
      expression in fibroblasts and mononuclear leukocytes in synergy with IFN-gamma
      and provide a mechanism for enhanced synovial chemokine levels in septic
      arthritis.
AB  - The CXC chemokine IFN-gamma-inducible protein-10 (IP-10/CXCL10) activates CXC
      chemokine receptor 3 (CXCR3) and attracts activated T cells and natural killer
      cells. Peripheral blood mononuclear cells (PBMC) produce low but significant
      amounts of IP-10/CXCL10 protein upon stimulation with double-stranded (ds) RNA,
      the Toll-like receptor 3 (TLR3) ligand. IFN-gamma is a superior IP
      10/CXCL10inducer. The bacterial TLR4 and TLR2 ligands, LPS and peptidoglycan
      (PGN), inhibit IFN-gamma- or dsRNA-dependent IP-10/CXCL10 production in PBMC,
      whereas IL-8/CXCL8 production was enhanced. In fibroblasts a different picture
      emerges with IFN-gamma inducing moderate and dsRNA provoking strong IP-10/CXCL10
      production. Furthermore, treatment of fibroblasts with IFN-gamma in combination
      with bacterial LPS or PGN results in a synergistic production of IP-10/CXCL10 and
      IL-8/CXCL8. The synergistic induction of IP-10/CXCL10 in fibroblasts is reflected
      by significantly enhanced IP-10/CXCL10 concentrations in synovial fluids of
      septic compared to osteoarthritis patients to reach on average higher levels than
      those of IL-8/CXCL8. These high amounts of IP-10/CXCL10 produced by connective
      tissue fibroblasts not only attract CXCR3 expressing activated Th1 cells and
      natural killer cells to sites of infection but may also antagonize the CCR3
      dependent attraction of Th2 lymphocytes and exert CXCR3-independent, defensin
      like antibacterial activity.

PMID- 14579284
TI  - The cyclin-dependent kinase inhibitors p27Kip1 and p21Cip1 are not essential in T
      cell anergy.
AB  - Recent evidence suggests that the cyclin-dependent kinase (Cdk) inhibitors
      p27Kip1 and p21Cip1 are important factors in T cell anergy, but it has remained
      unclear whether anergy can be induced in their absence. We therefore induced
      anergy by stimulation of purified T cells from wild-type, p21Cip1-/-, and p27Kip1
      /- mice with anti-CD3 antibodies. Anergic wild-type T cells were arrested in the
      G1 phase of the cell cycle with a high p27Kip1 protein level and low Cdk2
      activity. In p27-/- and p21-/- T cells, the pattern of protein expression was
      preserved, but Cdk2 activity was increased. To confirm the in vivo relevance of
      these data, anergy was induced by repeated injection of mice with staphylococcal
      enterotoxin B (SEB), which leads to partial deletion of the responsive Vbeta8+ T
      cell population and anergy in the remaining T cells. p21-/- mice and wild-type
      mice reacted similarly to this treatment. p27-/- mice showed reduced deletion of
      SEB-responsive T cells, but persisting T cells were anergic. These data indicate
      that other cell cycle regulators contribute to the cell cycle arrest of anergic T
      cells, as neither Cdk inhibitor is required for the induction of anergy.

PMID- 14579285
TI  - Bacterial DNA activates human neutrophils by a CpG-independent pathway.
AB  - Bacterial DNA stimulates macrophages, monocytes, B lymphocytes, NK cells, and
      dendritic cells in a CpG-dependent manner. In this work we demonstrate that
      bacterial DNA, but not mammalian DNA, induces human neutrophil activation as
      assessed by L-selectin shedding, CD11b upregulation, and stimulation of cellular
      shape change, IL-8 secretion, and cell migration. Induction of these responses is
      not dependent on the presence of unmethylated CpG motifs, as neutrophil
      stimulatory properties were neither modified by CpG-methylation of bacterial DNA
      nor reproduced by oligonucleotides bearing CpG motifs. We found that human
      neutrophils express Toll-like receptor (TLR) 9 mRNA. However, as expected for a
      CpG-independent mechanism, activation does not involve a TLR9-dependent signaling
      pathway; neutrophil stimulation was not prevented by immobilization of bacterial
      DNA or by wortmannin or chloroquine, two agents that inhibit TLR9 signaling. Of
      note, both single-stranded and double-stranded DNA were able to induce
      activation, suggesting that neutrophils might be activated by bacterial DNA at
      inflammatory foci even in the absence of conditions required to induce DNA
      denaturation. Our findings provide the first evidence that neutrophils might be
      alerted to the presence of invading bacteria through recognition of its DNA via a
      novel mechanism not involving CpG motifs.

PMID- 14579286
TI  - Anti-tumor immune responses and tumor regression induced with mimotopes of a
      tumor-associated T cell epitope.
AB  - Mimotopes provide an alternative to natural T cell epitopes for cancer immune
      therapy, as they can recruit and stimulate T cell repertoires that deviate from
      the repertoires engaged with the tumor and exposed to disease-related immune
      suppression. Here, mimotopes of a shared tumor-associated T cell epitope in
      cutaneous lymphoma were tested for their capacities to induce clinical and
      immunological responses in cancer patients. The mimotope sequences had been
      determined by a combinatorial peptide library approach without knowledge of the
      corresponding natural tumor-associated antigen. Vaccination with these mimotopes
      together with helper T cell-inducing antigens led to complete tumor remission in
      the two patients tested. After each booster vaccination, enhanced frequencies of
      mimotope-specific CD8+ T cells were detected in the peripheral blood of the
      patients, and the CTL proved to be cytotoxic and tumoricidal when tested in
      vitro. These data provide a first indication of clinical efficacy of mimotopes in
      cancer patients.

PMID- 14579287
TI  - The B subunit of Escherichia coli heat labile enterotoxin abrogates oral
      tolerance, promoting predominantly Th2-type immune responses.
AB  - Mucosal antigen encounter usually results in a state of systemic non
      responsiveness (tolerance). This failure to mount a protective response is a
      major hurdle to mucosal vaccine development. Hence, the identification of safe
      and effective mucosal adjuvants promoting protective immunity is of critical
      importance. The non-toxic B subunit of Escherichia coli heat labile
      enterotoxin(EtxB) is a potent nasal adjuvant; however, its usefulness following
      oral delivery is unconfirmed. We used DO11.10 chimeric mice to assess whether
      EtxB could abrogate tolerance to oral OVA. We show that admixing EtxB with OVA
      for oral immunization abrogates oral tolerance and results in a weak anti-OVA
      immune response. Importantly, EtxB profoundly modulated the nature of the
      response to subsequent parenteral challenge, promoting IgG1 in favor of IgG2a
      antibodies and depressing IFN-gamma production while elevating TGF-beta
      secretion. The addition of EtxB promoted T cell division, as assessed by loss of
      staining with carboxyfluorescein diacetate succinimidyl ester. Enhanced cell
      division promoted by EtxB was associated with T cell differentiation (increased
      numbers of CD45RBlow cells) in vivo, although dividing OVA-specific T cells were
      CD25-. These data suggest that although EtxB is a weak oral adjuvant, it can
      profoundly modulate the nature of the immune response to admixed antigen.

PMID- 14579288
TI  - Treponemal glycoconjugate inhibits Toll-like receptor ligand-induced cell
      activation by blocking LPS-binding protein and CD14 functions.
AB  - Spirochetes are well-known as causative agents of various chronic infectious
      diseases. Glycolipids of small-sized Treponema spirochetes have been shown to
      exhibit immunostimulating activities. In this study, we found that a
      glycoconjugate preparation obtained from Treponema medium (Tm-Gp), an
      intermediate-sized oral Treponema seen in subgingival plaque from patients with
      chronic periodontal diseases, diminished the LPS-induced activation of a human
      monocytic cell line, while TNF-alpha-induced activation was unaffected. NF-kappaB
      activation in Ba/F3 cells expressing murine Toll-like receptor (TLR) 4 and MD-2
      was inhibited by Tm-Gp in a CD14/LPS-binding protein (LBP)-dependent manner when
      stimulated with LPS or its active center lipid A but not when stimulated with
      Taxol. Tm-Gp blocked the binding of LPS to immobilized CD14 and LBP and inhibited
      nitric oxide (NO) production by a murine Mphi cell line following stimulation
      with peptidoglycan and LPS in the presence of FBS, while NO production in
      response poly (I:C) RNA or CpG DNA remained unaffected. The inhibitory effects of
      Tm-Gp seem to be attributable to the lipophilic portion of the glycoconjugate.
      These results indicate that T. medium contains a glycoconjugate possessing an
      inhibitory effect on TLR-mediated cell activation through interaction with LBP
      and CD14.

PMID- 14579289
TI  - Cholera toxin activates dendritic cells through dependence on GM1-ganglioside
      which is mediated by NF-kappaB translocation.
AB  - Cholera toxin (CT) is a potent adjuvant; however, the mechanism for its ability
      to enhance mucosal immunity has not been fully elucidated. We report here that CT
      exerts its adjuvant properties by signaling through the GM1 ganglioside receptor.
      When ganglioside-defective mice were given the antigen (Ag) ovalbumin (OVA) with
      CT by the oral route, CT failed to support either OVA-specific antibody or CD4+ T
      cell responses. In vitro treatment of murine bone marrow-derived dendritic cells
      (DC) with CT induced full maturation as evidenced by up-regulation of the
      costimulatory molecules, as well as by an enhanced ability to effectively present
      OVA for Ag-specific T cell responses. On the other hand, ganglioside-defective DC
      failed to differentiate to full function as Ag-presenting cells in response to
      CT. Since ganglioside-defective DC showed a mature phenotype after stimulation
      with lipopolysaccharide (LPS), the effects of CT on DC was independent of signal
      transduction through adjuvant receptor for LPS, the Toll-like receptor 4.
      Furthermore, CT also induced nuclear translocation of nuclear factor (NF)-kappaB
      in DC in a GM1-dependent fashion. These results highlight gangliosides expressed
      by DC for recognition of the non-self protein bacterial enterotoxin, which employ
      a unique signaling pathway to induce both innate and adaptive immunity.

PMID- 14579290
TI  - LIGHT, a new TNF superfamily member, is essential for memory T helper cell
      mediated activation of dendritic cells.
AB  - LIGHT is a recently identified member of the TNF superfamily that is up-regulated
      on activated T cells and can cooperate with CD40L to condition DC for the priming
      of CTL. In this report, we show that an intracellular pool of LIGHT is found
      selectively in some CD45RA-CD27+CD4+ "central" memory T cells and to a greater
      extent in some CD45RA-CD27-CD4+ effector memory T cells. LIGHT, like CD40L, is
      rapidly up-regulated on memory CD4+ T cells upon activation. Unlike CD40L, LIGHT
      up-regulation on naive T cells is delayed. Stimulation of DC with each subset of
      memory T cells in the presence of superantigen revealed that CD40L and LIGHT are
      required for optimal secretion of IL-12. Moreover, effector memory T cells, which
      can interact with DC in peripheral tissues, contribute to CCR7 induction on DC.
      LIGHT and CD40L can also regulate IL-12 production by CCR7+ DC capable of
      migration to lymph nodes. These data suggest that both LIGHT and CD40L may be
      involved in the maintenance or reactivation of secondary Th1 responses.

PMID- 14579291
TI  - Programmatic assessments of the clinical effectiveness of gynecologic liquid
      based cytology.

PMID- 14579292
TI  - Liquid-based cervical cytology.
AB  - BACKGROUND: The objective of the current study was to evaluate the applicability
      of liquid-based cytology in the Netherlands population screening program for
      cervical cancer. METHODS: A special committee performed an evaluation of all the
      available literature. Two methods were investigated: the AutoCytePrep system
      (currently known as ShurePath-system; TriPath Imaging, Burlington, NC) and the
      ThinPrep system (Cytyc, Boxborough, MA) for the detection of squamous epithelial
      abnormalities. All literature up to May 2000 was evaluated. RESULTS: For the
      AutoCytePrep system, there were indications that the detection rate for atypical
      squamous cells of undetermined significance (ASCUS) or higher had lower
      sensitivity compared with conventional screening. No definitive statement could
      be made concerning the value of the AutoCytePrep system for the detection rate of
      low-grade squamous intraepithelial lesions (LSIL) or higher and high-grade
      squamous intraepithelial lesions (HSIL) or higher because of conflicting results.
      For the ThinPrep system, there were indications that the detection rate of ASCUS
      or higher had a higher detection rate compared with conventional screening, with
      slightly lower specificity. It is likely that the detection rate of LSIL or
      higher with the ThinPrep system had greater sensitivity compared with
      conventional screening with almost unchanged specificity. In addition, it is
      likely that the detection rate of HSIL or higher with the ThinPrep system had a
      higher detection rate and greater absolute sensitivity compared with conventional
      screening with almost unchanged relative and absolute specificity. CONCLUSIONS:
      Further research that complies with the standards stated in the current study
      will be necessary to evaluate the applicability of the AutoCytePrep method.
      Further evaluation of the costs and benefits of the ThinPrep method should be
      undertaken to decide definitively whether to implement this method in the
      Netherlands population screening program.

PMID- 14579293
TI  - The significance of the Papanicolaou smear diagnosis of low-grade squamous
      intraepithelial lesion cannot exclude high-grade squamous intraepithelial lesion.
AB  - BACKGROUND: Cervical cytologic specimens that show a low-grade squamous
      intraepithelial lesion (LSIL) occasionally contain a few cells that are
      suspicious for, but not diagnostic of, a high-grade squamous intraepithelial
      lesion (HSIL). In such cases, a diagnosis of LSIL cannot exclude HSIL is
      rendered. The objective of the current study was to assess the positive
      predictive value (PPV) for HSIL in follow-up cervical biopsies for these cases.
      METHODS: One hundred forty-four women with a Papanicolaou (Pap) diagnosis of LSIL
      cannot exclude HSIL and their follow-up cervical biopsies were reviewed. Results
      were compared with a control group of 155 women with a Pap diagnosis of LSIL. A
      subset of biopsies was tested and typed for human papillomavirus (HPV) DNA by
      polymerase chain reaction amplification using consensus primers followed by
      restriction fragment length polymorphism analysis. HPVs were scored as low-risk
      or high-risk types. RESULTS: Women with LSIL cannot exclude HSIL had a higher
      incidence of HSIL (PPV = 29%) on follow-up cervical biopsy than the control group
      (PPV = 15%, P < 0.01). In addition, SIL, indeterminate grade was diagnosed in 10%
      of cervical biopsies in the study group as compared with 4% in controls. Review
      of Pap smears from the study group showed that there were 3 types of cells
      suspicious for a high-grade lesion: atypical squamous metaplastic cells (62%),
      atypical keratinized cells (20%), and dysplastic cells of borderline nuclear-to
      cytoplasm ratio (18%). HPV analysis confirmed the presence of high-risk HPV types
      in the study cases with high-grade cervical biopsies. CONCLUSIONS: Women with a
      Pap diagnosis of LSIL cannot exclude HSIL appear to be more likely to harbor a
      high-grade lesion than those diagnosed with LSIL alone. Its use appears
      warranted. Women with this diagnosis merit appropriate clinical follow-up to
      exclude HSIL.

PMID- 14579294
TI  - Fine-needle aspiration biopsy of the central nervous system performed freehand
      under computed tomography guidance without stereotactic instrumentation.
AB  - BACKGROUND: Biopsy of the central nervous system (CNS) has been reported
      previously using relatively large-caliber (12-17-gauge) biopsy instruments with
      or without stereotactic guidance. In this series, fine-needle aspiration biopsies
      (FNABs) were performed using a smaller diameter needle to evaluate mass lesions
      of the CNS. METHODS: One hundred thirty FNABs were performed freehand under
      computed tomography (CT) guidance without stereotactic instrumentation guidance
      using a 22-gauge needle. RESULTS: A definitive diagnosis was rendered in 97 of
      130 FNABs (75%), including glioblastoma multiforme (GBM) (n = 33 biopsies);
      anaplastic astrocytoma (n = 14 biopsies); metastatic carcinoma (n = 13 biopsies);
      low-grade astrocytoma (LGA) (n = 10 biopsies); lymphoma (n = 7 biopsies);
      oligodendroglioma (n = 5 biopsies); reactive gliosis (n = 2 biopsies); and
      abscess (n = 13 biopsies), with the infectious agent identified in 7 of 13
      biopsies. Immunohistochemistry was employed in 51 biopsies to assist in
      determining either the cell type or the infectious agent. Indefinite diagnoses
      were rendered in 33 patients (25%), including LGA versus gliosis (n = 8
      patients), necrosis and/or inflammation (n = 3 patients), nondiagnostic material
      (n = 17 patients), suspicious for lymphoma (n = 2 patients), suspicious for GBM
      (n = 2 patients), and high-grade neoplasm not otherwise classified (n = 1
      patient). There was no morbidity or mortality attributed to the procedure.
      CONCLUSIONS: FNAB of CNS mass lesions established a diagnosis based on cytologic
      interpretation in 75% of biopsies without morbidity or mortality. Because
      morbidity and mortality rates in CT-guided biopsies utilizing stereotactic
      techniques with large-caliber needles have been reported as high as 14% and 4.7%,
      respectively, freehand FNAB under CT guidance may be a preferred initial method
      for evaluating mass lesions of the CNS.

PMID- 14579295
TI  - Yield of endoscopic ultrasound-guided fine-needle aspiration biopsy in patients
      with suspected pancreatic carcinoma.
AB  - BACKGROUND: Although atypical or suspicious cytology may support a clinical
      diagnosis of a malignancy, it is often not sufficient for the implementation of
      therapy in patients with pancreatic carcinoma. Endoscopic ultrasound-guided fine
      needle aspiration biopsy (EUS-FNAB) is a relatively new method for obtaining
      cytology samples, and one that may decrease the number of atypical/suspicious
      diagnoses. The goals of the current study were to prospectively evaluate the
      yield of EUS-FNAB in the diagnosis of patients presenting with solid pancreatic
      lesions and to evaluate the significance of atypical, suspicious, and false
      negative aspirates. METHODS: All patients who presented with a solid pancreatic
      lesion and underwent EUS-FNAB over a 13-month period were included in the current
      study. One endoscopist performed all EUS-FNABs. On-site evaluation of specimen
      adequacy by a cytopathologist was available for each case. Follow-up included
      histologic correlation (n = 21) and clinical and/or imaging follow-up (n = 80),
      including 38 patients who died of the disease. RESULTS: EUS-FNABs were obtained
      from 101 patients (mean age, 62 +/- 11.8 years; age range, 34-89 years). The male
      to-female ratio was 2:1. Sixty-five percent of the lesions were located in the
      head of the pancreas, 12% were located in the uncinate, 17% were located in the
      body, and 6% were located in the tail. The mean size of the tumors was 3.3 cm
      (range, 1.3-7 cm). A median of 4 needle passes were performed (range, 1-11 needle
      passes). Sixty-two biopsies (61.4%) were interpreted as malignant on cytologic
      evaluation, 5 (5%) as suspicious for a malignancy, 6 (5.9%) as
      atypical/indeterminate, and 26 (25.7%) as benign processes. Of the 76 malignant
      lesions, 71 were adenocarcinomas, 3 were neuroendocrine tumors, 1 was a lymphoma,
      and 1 was a metastatic renal cell carcinoma. All except one of the
      suspicious/atypical aspirates were subsequently confirmed to be malignant.
      Agreement was complete for the atypical cases. Among the suspicious cases, 2 of
      the 5 were identified as carcinoma by one cytopathologist and as suspicious
      lesions by the other, yielding a 40% disagreement rate between the 2
      cytopathologists. Therefore, for the 10 atypical or suspicious cases that later
      were confirmed to be malignant, the final diagnosis of malignant disease was not
      made due to scant cellularity that could be attributed to sampling error in 8
      cases and to interpretative disagreement in 2 cases (20%). All four false
      negative diagnoses were attributed to sampling error. Two percent of all biopsies
      were inadequate for interpretation. Of the 99 adequate specimens, 72 yielded true
      positive results, 23 yielded true-negative results, and 4 yielded false-negative
      results. No false-positives were encountered. Therefore, the sensitivity,
      specificity, positive predictive value, and negative predictive value of EUS-FNAB
      for solid pancreatic masses were 94.7% (95% confidence interval [CI], 89.7
      99.8%), 100%, 100%, and 85.2% (95% CI, 71.8-98.6%), respectively. CONCLUSIONS:
      EUS-FNAB is a safe and highly accurate method for tissue diagnosis of patients
      with solid pancreatic lesions. Patients with suspicious and atypical EUS-FNAB
      aspirates deserve further clinical evaluation.

PMID- 14579296
TI  - Cytomorphologic spectrum of small lymphocytic lymphoma in patients with an
      accelerated clinical course.
AB  - BACKGROUND: Patients with transformed large cell lymphoma (TLCL), or Richter
      syndrome, and patients with small lymphocytic lymphoma/leukemia (SLL) in
      accelerated phase (SLL-AP) frequently undergo fine-needle aspiration (FNA) to
      elucidate the cause of massive lymphadenopathy and a worsening clinical
      condition. It is well known that patients with Richter syndrome have poor
      clinical outcomes as a result of the biologic aggressiveness of the transformed
      large cells that often are refractory to therapy. The objective of this study was
      to evaluate reliable criteria for recognizing SLL-AP and SLL in transformation
      that are needed to determine the appropriate clinical management of individual
      patients. METHODS: FNA specimens from 20 patients with SLL, 26 patients with SLL
      AP, and 13 patients with TLCL or Richter syndrome were identified based on the
      reported diagnosis. Patients were included only if they had histologically
      confirmed SLL that also satisfied the immunophenotypic criteria of CD5/CD23
      coexpression with negative CD10 and < 55% prolymphocytes. On the basis of an
      initial blind review of routinely stained slides from the FNA specimens, the
      authors defined four groups based on a consensus review diagnosis: Group 1:
      typical SLL; Group 2: low-grade SLL-AP; Group 3: high-grade SLL-AP; and Group 4:
      TLCL. Cytomorphologic features, including the proportion of intermediate-to-large
      cells with prominent nucleoli and intermediate-sized plasmacytoid lymphoid cells,
      increased numbers of mitotic figures, the presence of apoptotic bodies and
      necrosis, and a myxoid/dirty background, were considered features that indicated
      an accelerated phase. Specimens that had more than two grades of diagnostic
      discrepancy compared with the original reported diagnosis were reexamined using a
      Ki-67 immunostaining labeling index to reach a final review diagnosis. RESULTS:
      On the basis of the review diagnosis, the specimens were recategorized as
      follows: Group 1: 20 patients with typical SLL; Group 2: 13 patients with low
      grade-SLL-AP; Group 3: 16 patients with high-grade SLL-AP; and Group 4: 10
      patients with TLCL. The mean Ki-67 labeling index (%) was correlated with the
      morphologic progression of SLL as follows: Group 1: 11%; Group 2: 16%; Group 3:
      34%; and Group 4: 48%. The follow-up by subsequent FNA or biopsy demonstrated
      large cell transformation in 25% of patients in Group 1, 25% of patients in Group
      2, and 100% of patients in Group 3. Among the clinical parameters, increased
      value of serum beta2-microglobulin and lactic dehydrogenase (LDH) levels were
      found to be well correlated with the cytomorphologic progression of SLL/chronic
      lymphocytic leukemia. CONCLUSIONS: Aspirates from patients who had signs and
      symptoms clinically suspicious for SLL-AP demonstrated a spectrum of
      cytomorphologic features, ranging from low-grade SLL-AP and high-grade SLL-AP to
      TLCL. The results showed that the Ki-67 labeling index, as determined by
      immunohistochemical studies in FNA specimens, and the levels of serum beta2
      microglobulin and LDH are valuable diagnostic adjuncts for recognizing a subset
      of patients with SLL-AP or SLL in transformation who may require more aggressive
      therapy.

PMID- 14579297
TI  - Cytologic findings of marginal zone lymphoma.
AB  - BACKGROUND: Low-grade lymphomas can be difficult to diagnose in cytology
      specimens, especially marginal zone B-cell lymphomas (MZLs). MZL is a low-grade
      lymphoma characterized by a heterogeneous lymphoid population, which can be
      difficult to distinguish from reactive processes in cytology specimens. METHODS:
      Fourteen cytology specimens of MZL from 11 patients with histologically confirmed
      MZL (n = 10) or flow cytometry (FC)-confirmed MZL (n = 1) were reviewed,
      including 13 fine-needle aspiration biopsy (FNAB) specimens (salivary gland, n =
      6; lung, n = 3; lymph node, n = 2; breast, n = 1; and soft tissue, n = 1) and 1
      pleural effusion specimen. Cytologic preparations included air-dried and alcohol
      fixed direct smears, ThinPrep(R) slides, and cell blocks. FC studies were
      available in six specimens. RESULTS: All 13 FNAB specimens were composed
      predominantly of intermediate-sized lymphoid cells with interspersed small, round
      lymphocytes and transformed cells. The intermediate-sized cells displayed a
      moderate amount of cytoplasm, slight nuclear membrane irregularities, and
      inconspicuous-to-absent nucleoli. The pleural fluid contained mostly small-to
      intermediate-sized, round lymphocytes. In 10 specimens, the intermediate-sized
      cells often showed plasmacytoid morphology, which were seen best in Diff-Quik
      (Mercedes Scientific Co., Inc., Sarasota, FL)-stained slides. Monocytoid cells (n
      = 6 specimens), plasma cells (n = 7), lymphohistiocytic aggregates (n = 11), and
      tingible body macrophages (n = 5) were variably identified. Lymphoepithelial
      lesions were not observed. Three specimens with FC studies showed a phenotype
      compatible with MZL, and three specimens were nondiagnostic. CONCLUSIONS:
      Cytologic features suggestive of MZL included abundant intermediate-sized
      lymphoid cells with mild atypia in a background of small lymphocytes and
      transformed cells, often with plasmacytoid morphology. Flow cytometry was
      beneficial only in selected MZL cytology specimens. Surgical correlation may be
      necessary to confirm the diagnosis.

PMID- 14579298
TI  - HER-2/neu amplification by fluorescence in situ hybridization in cytologic
      samples from distant metastatic sites of breast carcinoma.
AB  - BACKGROUND: Amplification of the HER-2/neu oncogene has been proposed as a target
      for antibody-based therapies and as a predictor of chemoresponsiveness in
      advanced breast carcinoma. Few studies have concentrated on HER-2/neu gene
      evaluation by fluorescence in situ hybridization (FISH) on distant metastatic
      sites and none have been performed on cytologic samples. The current study
      evaluated HER-2/neu amplification by FISH on cytologic samples obtained from
      distant metastatic lesions of breast carcinoma to update HER-2/neu
      characterization through a safe and easier procedure than biopsy. METHODS: Twenty
      two cytologic samples from distant metastases (12 hepatic samples, 4 skin
      samples, 3 pleural samples, and 3 peritoneal samples) were submitted to HER-2/neu
      evaluation by FISH. Seventeen corresponding primary breast tumors also were
      evaluated by FISH on paraffin histologic sections or on destained archival
      cytologic smears. RESULTS: Seven of the 22 metastases (32%) were amplified.
      Amplification was observed in 4 of the 12 liver metastases, in 1of the 3 ascitic
      fluid specimens, and in 2 of the 4 skin metastases. In all the three pleural
      fluid specimens, HER-2/neu was unamplified. Matched results from primary and
      metastatic lesions were obtained in 14 cases (5 were amplified and 9 were
      unamplified on both primary and metastatic tumors). CONCLUSIONS: The results of
      the current study emphasized the feasibility and advantages of two rapid and very
      informative techniques, such as fine-needle aspiration biopsy and FISH. Both
      procedures were performed to ascertain the malignant nature of a suspicious
      lesion and to obtain predictive markers for response. Since the advent of
      trastuzumab, the characterization of the molecular profile in metastatic breast
      disease has become increasingly important for targeted therapy selection.

PMID- 14579299
TI  - Misclassification of cytologic diagnoses in patients with follicular lesions or
      follicular neoplasms of the thyroid gland.

PMID- 14579301
TI  - Stability of archived liquid-based cytologic specimens.

PMID- 14579302
TI  - Adsorption of actin at the air-water interface: a monolayer study.
AB  - The intrinsic surface activity of the contractile protein actin has been
      determined from surface tension measurements using the Wilhelmy hanging-plate
      method. Actin, a very soluble protein, moves from the subphase to the air-water
      interface to make a film. In the absence of magnesium, actin is monomeric and is
      known as G-actin. During the compression the monomers change their conformation
      or orientation at the interface and they are then pushed reversibly into the
      subphase upon further compression. No collapse occurs. Actin monomers in the
      presence of magnesium become activated; at concentrations greater than some
      critical value, actin polymerizes to form filaments of F-actin. The actin
      filaments have a higher surface activity than the actin monomers either because
      they are more hydrophobic or because F-actin, a rigid polymer, is much more
      efficient at creating excluded volume. The actin filaments then form a rigid film
      at the interface that collapses when the surface area is decreased. At less than
      the critical concentration, the actin monomers are present in the subphase in
      their activated form. However, their concentration increases at the interface
      during film compression until the critical concentration is reached. The surface
      pressure isotherm in this case has the characteristics of a G-actin film at the
      beginning of the compression and of an F-actin film at the end of the compression
      process.

PMID- 14579303
TI  - Binding of copper(II) ions to the polyproline II helices of PEVK modules of the
      giant elastic protein titin as revealed by ESI-MS, CD, and NMR.
AB  - Titin, a family of giant elastic proteins, constitutes an elastic sarcomere
      matrix in striated muscle. In the I-band region of the sarcomere, the titin PEVK
      segment acts as a molecular spring to generate elasticity as well as sites of
      adhesion with parallel thin filaments. Previously, we reported that PEVK consists
      of tandem repeats of 28 residue modules and that the "polyproline II-coil" motif
      is the fundamental conformational motif of the PEVK module. In order to
      characterize the factors that may affect and alter the PPII-coil conformational
      motifs, we have initiated a systematic study of the interaction with divalent
      cations (Cu2+, Ca2+, Zn2+, and Ni2+) and a conformational profile of PEVK
      peptides (a representative 28-mer peptide PR: PEPPKEVVPEKKAPVAPPKKPEVPPVKV and
      its subfragments PR1: kvPEPPKEVVPE, PR2: VPEKKAPVAPPK, PR3: KPEVPPVKV). UV-Vis
      absorption difference spectra and CD spectra showed that Cu2+ bound to PR1 with
      high affinity (20 microM), while its binding to PR2 and PR3 as well as the
      binding of other cations to all four peptides were of lower affinity (>100
      microM). Conformational studies by CD revealed that Cu2+ binding to PR1 resulted
      in a polyproline II to turn transition up to a 1:2 PR1/Cu2+ ratio and a coil to
      turn transition at higher Cu2+ concentration. ESI-MS provided the stoichiometry
      of PEVK peptide-Cu2+ complexes at both low and high ion strength, confirming the
      specific high affinity binding of Cu2+ to PR1 and PR. Furthermore, NMR and ESI
      MS/MS fragmentation analysis elucidated the binding sites of the PEVK peptide
      Cu2+ complexes at (-2)KVPE2, 8VPE10, 13APV15, and 22EVP24. A potential
      application of Cu2+ binding in peptide sequencing by mass spectrometry was also
      revealed. We conclude that Cu2+ binds and bends PEVK peptides to a beta-turn-like
      structure at specific sites. The specific targeting of Cu2+ towards PPII is
      likely to be of significant value in elucidating the roles of PPII in titin
      elasticity as well as in interactions of proline-rich proteins.

PMID- 14579304
TI  - Crystal structure of achiral nonapeptide Boc-(Aib-DeltaZPhe)4-Aib-OMe at atomic
      resolution: evidence for a 3(10)-helix.
AB  - An x-ray crystallographic analysis was carried out for Boc-(Aib-DeltaZPhe)4-Aib
      OMe (1: Boc = t-butoxycarbonyl; Aib = alpha-aminoisobutyric acid; DeltaZPhe = Z
      alpha,beta-didehydrophenylalanine) to provide the precise conformational
      parameters of the octapeptide segment -(Aib-DeltaZPhe)4-. Peptide 1 adopted a
      typical 3(10)-helical conformation characterized by <phi> = +/-55.8 degrees (50
      degrees -65 degrees), <psi> = +/-26.7 degrees (15 degrees -45 degrees), and
      <omega> = +/-179.5 degrees (168 degrees -188 degrees) for the average values of
      the -(Aib-DeltaZPhe)4- segment (the range of the eight values). The 3(10)-helix
      contains 3.1 residues per turn, being close to the "perfect 3(10)-helix"
      characterized by 3.0 residues per turn. NMR and Fourier transform infrared (FTIR)
      spectroscopy revealed that the 3(10)-helical conformation at the atomic
      resolution is essentially maintained in solution. Energy minimization of peptide
      1 by semiempirical molecular orbital calculation converged to a 3(10)-helical
      conformation similar to the x-ray crystallographic 3(10)-helix. The preference
      for a 3(10)-helix in the -(Aib-DeltaZPhe)4- segment is ascribed to strong
      inducers of the 3(10)-helix inherent in Aib and DeltaZPhe residues-in particular,
      the Aib residues tend to stabilize a 3(10)-helix more effectively. Therefore, the
      -(Aib-DeltaZPhe)4- segment is useful to rationally design an optically inactive
      3(10)-helical backbone, which will be of great importance to provide novel
      insights into noncovalent and covalent chiral interactions of a helical peptide
      with a chiral molecule.

PMID- 14579305
TI  - Physicochemical characterization of branched chain polymeric polypeptide carriers
      based on a poly-lysine backbone.
AB  - A systematic study is reported on the physicochemical characteristics of two
      branched chain polymers (based on a poly-L-lysine backbone) with a general
      formula poly[Lys-(DL-Alam-Xi)], where X = Orn (OAK) or N-acetyl-Glu (Ac-EAK) and
      m approximately equal to 3, using surface pressure and fluorescence polarization
      methods. These data are compared with those of the linear poly(L-Lys) from which
      OAK and Ac-EAK are derived. These two polymers show a moderate surface activity,
      able to form stable monomolecular layers at the air-water interface. Poly(L-Lys),
      the most hydrophilic, has the lowest surface activity. The interaction of these
      polymers with phospholipid bilayers either neutral or negatively charged was
      studied with vesicles labeled with two fluorescent probes: ANS and DPH. Results
      indicate that these polymers are able to accommodate in their internal structure,
      mainly through electrostatic interactions, a certain amount of ANS marker
      molecules, but fluorescence increases of the ANS-polypeptide complexes were so
      low that its influence in further polarization measurements could be discarded.
      After interaction with liposomes, these polymers induce an increase in the
      polarization of the probes, thus indicating a rigidification of the bilayers.
      Electrostatic forces seem to be very important in this interaction; cationic
      polymers are clearly more active, with PG-containing liposomes, than Ac-EAK.
      Moreover, in these assays poly(L-Lys) behaves as the more active compound. This
      fact is probably due to its major ability to form alpha-helical structures that
      could insert easily in the bilayers. These results indicate that the polymeric
      structures studied can be used as carriers for biologically active molecules,
      because their interactions with bilayers remain soft and have a positive effect
      on the stability of the membranes.

PMID- 14579306
TI  - Structural transitions involved in a novel amyloid-like beta-sheet assemblage of
      tripeptide derivatives.
AB  - Self-assembly of two tripeptide derivatives containing three nonpolar isoleucine
      moieties and polar oxyethylene groups are studied in methanol. Peptide A
      [CH3(OCH2CH2)3OCH2CO(Ile)3OCH3] and peptide B [CH3(OCH2CH2)3OCH2CO(Ile)3NH
      (CH2CH2O)3CH3] take a mixture of unordered and helical conformation at low
      concentration (8.5 x 10(-4) M). However, at high concentration (2 x 10(-3) M),
      both the peptide showed significant increase in the helical conformation. An
      interesting conformational transition of peptides A and B at various methanol
      contents was observed in the solvated films of these compounds by spectroscopic
      methods like the far-uv circular dichroism and Fourier transform infrared (FT-IR)
      techniques. Peptide B, which contains more polar oxyethylene groups than A,
      showed a highly cooperative conformational transition when the methanol content
      was decreased. This transition was characterized by a large increase of beta
      sheet, retaining a alpha-helical contribution. Peptide A showed a conformational
      transition resulting in a beta-sheet in the aggregated state. From the CD
      spectra, the ratio in the ellipticity indicates that peptide B forms twisted
      antiparallel beta-sheet conformation, whereas peptide A takes a parallel beta
      sheet conformation. The results obtained in this work indicates the role of polar
      derivatization on the conformational preference of peptides having similar
      sequence.

PMID- 14579307
TI  - Spectroscopic investigation on gel-forming beta-sheet assemblage of peptide
      derivatives.
AB  - The conformational studies of peptide derivatives A and B in a gel state were
      studied by using circular dichroism (CD), Fourier transformed infrared (FTIR),
      and fluorescence spectroscopic techniques. Birefringence and electron microscopic
      studies were carried out to characterize the morphological aspects of the fibrils
      in the gel. The FTIR spectra of the peptides show the absence of free NH in the
      gel state, implying that the intermolecular hydrogen-bond formation is the
      driving force for the aggregation. The CD spectrum of the peptide gels shows the
      presence of antiparallel and parallel beta-sheet conformation for peptide
      derivatives A and B, respectively. Electron microscopic studies (EM) of the
      peptide derivatives A and B reveal that peptide A formed rigid, rod-like
      structures without cross-linking and peptide B formed loose fibrils organized
      into highly noncovalently cross-linked mesh-like structural aggregates. Peptide A
      was much more soluble in alcoholic solvents than peptide B, and no birefringence
      was observed with Congo red (CR) staining in the temperature range of 0-80
      degrees C. The spectroscopic studies indicate that peptide B consists of domains
      having a significant amount of beta-sheet structure and exhibiting golden yellow
      birefringence between 53 and 56 degrees C when stained with Congo red. On the
      other hand, peptide A gives no evidence of birefringence under polarized light.
      Fluorescence probe binding studies with pyrene in gel state with peptides A and B
      indicates the polarity in the interior of the aggregates. The data presented in
      the present work indicate that peptide B forms fibrils, which is similar to
      amyloid aggregates that are present in biological systems.

PMID- 14579308
TI  - Mechanism-based protein design: attempted "nucleation-condensation" approach to a
      possible minimal helix-bundle protein.
AB  - In an intended mechanism-based de novo approach, a 22-mer peptide was so designed
      as to make it both a stereochemically nucleatable and hydrophobically condensable
      minimal globular protein. Framework-like nucleation of a triple-helix bundle was
      targeted by employing as folding nucleators composite beta-turns that could both
      nucleate helices and place them in close juxtaposition for possible interhelical
      interaction. To promote the targeted triple-helix bundle to condense as a
      globular protein, an amphipathic sequence pattern was adopted for possible
      hydrophobic interhelical interaction. A predominantly helicogenic 22-mer
      amphipathic peptide was thus designed, punctuating it with composite type II'-III
      and type II-Asx type beta-turns as the helix nucleators cum chain reversal
      elements. The peptide made by solid-phase synthesis was shown by NMR and CD to be
      a nascent and distorted triple-helix bundle in a trifluoroethanol (TFE)-water
      mixture, but more or less a random coil in water. A fold nucleation effect is
      evident in the TFE-water mixture, but apparently the hydrophobic effect cannot
      sustain the peptide conformational order in water. A lack of synergy between
      folding nucleation and hydrophobic condensation of the peptide is possible.
      Indeed, a mismatch between the sequential H,P pattern of the peptide and its
      nascent-type globular fold in a TFE-water mixture is evident based on a simulated
      annealing study guided by NMR.

PMID- 14579309
TI  - Speed-up of DNA melting algorithm with complete nearest neighbor properties.
AB  - We describe an optimized algorithm, which is faster and more accurate compared to
      previously described algorithms, for computing the statistical mechanics of
      denaturation of nucleic acid sequences according to the classical Poland-Scheraga
      type of model. Nearest neighbor thermodynamics has been included in a complete
      and general way, by rigorously treating nearest neighbor interactions, helix end
      interactions, and isolated base-pairs. This avoids the simplifications of
      previous approaches and achieves full generality and controllability with respect
      to thermodynamic modeling. The algorithm computes subchain partition functions by
      recursion, from which various quantitative aspects of the melting process are
      easily derived, for example the base-pairing probability profiles. The algorithm
      represents an optimization with respect to algorithmic complexity of the
      partition function algorithm of Yeramian et al. (Biopolymers 1990, 30, 481-497):
      we reduce the computation time for a base-pairing probability profile from O(N2)
      to O(N), where N is the sequence length. This speed-up comes in addition to the
      speed-up due to a multiexponential approximation of the loop entropy factor as
      introduced by Fixman and Freire22 and applied by Yeramian et al. The speed-up,
      however, is independent of the multiexponential approximation and reduces time
      from O(N3) to O(N2) in the exact case. A method for representing very large
      numbers is described, which avoids numerical overflow in the partition functions
      for genomic length sequences. In addition to calculating the standard base
      pairing probability profiles, we propose to use the algorithm to calculate
      various other probabilities (loops, helices, tails) for a more direct view of the
      melting regions and their positions and sizes. This can provide a better
      understanding of the physics of denaturation and the biology of genomes.

PMID- 14579310
TI  - Small-angle x-ray scattering studies of metastable intermediates of beta
      lactoglobulin isolated after heat-induced aggregation.
AB  - Small-angle x-ray scattering was used for studying intermediate species, isolated
      after heat-induced aggregation of the A variant of bovine beta-lactoglobulin. The
      intermediates were separated in two fractions, the heated metastable dimer and
      heated metastable oligomers larger than the dimer. The pair distance distribution
      functions for the two intermediate fractions as well as for the native protein
      have been obtained by indirect Fourier transformation. In addition, the
      scattering intensity data for samples of the native protein at different
      concentrations were fitted using a combination of monomer and dimer form factors,
      which provides an estimate of the amount of monomer in solutions. By subtracting
      the contribution from the monomer, the scattering intensity from the dimer of the
      native protein can be determined and compared with the results for the metastable
      dimer. An ellipsoidal model was used to fit the data for the metastable dimer,
      and for comparison the same analysis was performed on the dimer of the native
      protein. The results show that the metastable dimer is more elongated than the
      dimer of the native protein and it occupies a volume 1.4-fold larger, in
      agreement with a more loose, partially unfolded conformation. The same
      ellipsoidal model was used to analyze the data for the fraction of larger
      metastable oligomers. In this case, an even more elongated ellipsoid was
      obtained, suggesting a linear association of monomers in the oligomers.

PMID- 14579311
TI  - Brownian dynamics simulations of ion atmospheres around polyalanine and B-DNA:
      effects of biomolecular dielectric.
AB  - We have extended an earlier Brownian dynamics simulation algorithm for simulating
      the structural dynamics of ions around biomolecules to accommodate dielectric
      inhomogeneity. The electrostatic environment of a biomolecule immersed in water
      was obtained by numerically solving the Poisson equation with the biomolecule
      treated as a low dielectric region and the solvent treated as a high dielectric
      region. Instead of using the mean-field type approximations of ion interactions
      as in the Poisson-Boltzmann model, the ions were treated explicitly by allowing
      them to evolve dynamically under the electrostatic field of the biomolecule. This
      model thus accounts for ion-ion correlations and the finite-size effects of the
      ions. For a 13-residue alpha-helical polyalanine and a 12-base-pair bp B-form
      DNA, we found that the choice of the dielectric constant of the biomolecule has
      much larger effects on the mean ionic structure around the biomolecule than on
      the fluctuational and dynamical properties of the ions surrounding the
      biomolecule.

PMID- 14579312
TI  - Structure-activity relationships in the hydrophobic interactions of polyphenols
      with cellulose and collagen.
AB  - Polyphenol interactions with both cellulose and collagen in the solid state have
      been studied by using chromatography on cellulose and by evaluating the
      hydrothermal stability of the polyphenol treated sheepskin collagen. Twenty-four
      polyphenolic compounds were studied, including seven glucose-based gallotannins,
      five polyalcohol-based gallotannins, and twelve ellagitannins. In the cellulose
      polyphenols systems, the polyphenol's affinity to cellulose is positively
      correlated with their molecular masses, the number of galloyl groups, and their
      hydrophobicity (logP). The polyphenol treatment increased the hydrothermal
      stability of collagen samples, and such effects are also positively correlated
      with the molecular masses, total number of galloyl groups and the hydrophobicity
      of polyphenols. Ellagitannins showed much weaker interactions with both
      biopolymers than gallotannins having similar molecular mass, the same number of
      galloyl groups, and the same number of phenolic hydroxyl groups. It is concluded
      that, for the polyphenol interactions with both cellulose and collagen, (1) the
      galloyl group of polyphenols is the functional group; (2) the strength of
      interactions are positively correlated with molecular size, the number of galloyl
      groups and the hydrophobicity of polyphenols; (3) the hydrophobic interactions
      are of great significance; and (4) the interactions are strongly dependent on the
      flexibility of galloyl groups.

PMID- 14579313
TI  - DNA deformation energetics and protein binding.
AB  - The formation of protein-DNA complexes often involves deformation of the DNA
      double helix. We have calculated the energy necessary to produce this deformation
      in 71 crystallographically determined complexes, using internal coordinate energy
      optimization with the JUMNA program and a generalized Born continuum solvent
      treatment. An analysis of the data allows deformation energy to be interpreted in
      terms of both local and global structural changes. We find that, in the majority
      of complexes, roughly 60% of the deformation energy corresponds to backbone
      distortion. It is also found that large changes in stacking and pairing energies
      are often compensated for by other, longer range, stabilizing factors. Some
      deformations, such as base opening, can be large, but only-produce local
      energetic effects. In terms of backbone distortions, the angle alpha, most often
      involved in alphagamma transitions, makes the most significant energetic
      contribution. This type of transition is twice as costly as those involving beta,
      or coupled epsilonzeta changes. Sugar amplitude changes are also energetically
      significant, in contrast to changes in phase angles.

PMID- 14579314
TI  - The solution structure of frenatin 3, a neuronal nitric oxide synthase inhibitor
      from the giant tree frog, Litoria infrafrenata.
AB  - The peptide frenatin 3 is a major component of the skin secretion of the
      Australian giant tree frog, Litoria infrafrenata. Frenatin 3 is 22 amino acids in
      length, and shows neither antimicrobial nor anticancer activity. It inhibits the
      production of nitric oxide by the enzyme neuronal nitric oxide synthase at a
      micromolar concentration by binding to its regulatory protein, Ca2+ calmodulin, a
      protein known to recognize and bind amphipathic alpha-helices. The solution
      structure of frenatin 3 has been investigated using NMR spectroscopy and
      restrained molecular dynamics calculations. In trifluoroethanol/water mixtures,
      the peptide forms an amphipathic alpha-helix over residues 1-14 while the C
      terminal eight residues are more flexible and less structured. The flexible
      region may be responsible for the lack of antimicrobial activity. In water,
      frenatin 3 exhibits some alpha-helical character in its N-terminal region.

PMID- 14579321
TI  - CASP5. Proceedings of the 5th Meeting on the Critical Assessment of Techniques
      for Protein Structure Prediction. 1-5 December 2002, Asilomar, California, USA.

PMID- 14579322
TI  - Critical assessment of methods of protein structure prediction (CASP)-round V.
AB  - This article provides an introduction to the special issue of the journal
      Proteins dedicated to the fifth CASP experiment to assess the state of the art in
      protein structure prediction. The article describes the conduct, the categories
      of prediction, and the evaluation and assessment procedures of the experiment. A
      brief summary of progress over the five CASP experiments is provided. Related
      developments in the field are also described.

PMID- 14579323
TI  - CASP5 target classification.
AB  - This report summarizes the Critical Assessment of Protein Structure Prediction
      (CASP5) target proteins, which included 67 experimental models submitted from
      various structural genomics efforts and independent research groups. Throughout
      this special issue, CASP5 targets are referred to with the identification numbers
      T0129-T0195. Several of these targets were excluded from the assessment for
      various reasons: T0164 and T0166 were cancelled by the organizers; T0131, T0144,
      T0158, T0163, T0171, T0175, and T0180 were not available in time; T0145 was
      "natively unfolded"; the T0139 structure became available before the target
      expired; and T0194 was solved for a different sequence than the one submitted.
      Table I outlines the sequence and structural information available for CASP5
      proteins in the context of existing folds and evolutionary relationships. This
      information provided the basis for a domain-based classification of the target
      structures into three assessment categories: comparative modeling (CM), fold
      recognition (FR), and new fold (NF). The FR category was further subdivided into
      homologues [FR(H)] and analogs [FR(A)] based on evolutionary considerations, and
      the overlap between assessment categories was classified as CM/FR(H) and
      FR(A)/NF. CASP5 domains are illustrated in Figure 1. Examples of nontrivial links
      between CASP5 target domains and existing structures that support our
      classifications are provided.

PMID- 14579324
TI  - Assessment of homology-based predictions in CASP5.
AB  - This report describes the assessment of the homology-based predictions submitted
      to the fifth edition of the Critical Assessment of Methods for Protein Structure
      Prediction (CASP5) experiment. We assessed the ability of the methods to predict
      the overall fold, the portions of the structure that differ substantially between
      the target protein and its closest structural homologue and the conformation of
      the side-chains. We also compared the results with those obtained in previous
      editions of the experiment and derived some general conclusions about the state
      of the art of comparative modeling methods and their usefulness for
      experimentalists.

PMID- 14579325
TI  - A "FRankenstein's monster" approach to comparative modeling: merging the finest
      fragments of Fold-Recognition models and iterative model refinement aided by 3D
      structure evaluation.
AB  - We applied a new multi-step protocol to predict the structures of all targets
      during CASP5, regardless of their potential category. 1) We used diverse fold
      recognition (FR) methods to generate initial target-template alignments, which
      were converted into preliminary full-atom models by comparative modeling. All
      preliminary models were evaluated (scored) by VERIFY3D to identify well- and
      poorly-folded fragments. 2) Preliminary models with similar 3D folds were
      superimposed, poorly-scoring regions were deleted and the "average model"
      structure was created by merging the remaining segments. All template structures
      reported by FR were superimposed and a composite multiple-structure template was
      created from the most conserved fragments. 3). The average model was superimposed
      onto the composite template and the structure-based target-template alignment was
      inferred. This alignment was used to build a new (intermediate) comparative model
      of the target, again scored with VERIFY3D. 4) For all poorly scoring regions
      series of alternative alignments were generated by progressively shifting the
      "unfit" sequence fragment in either direction. Here, we considered additional
      information, such as secondary structure, placement of insertions and deletions
      in loops, conservation of putative catalytic residues, and the necessity to
      obtain a compact, well-folded structure. For all alternative alignments, new
      models were built and evaluated. 5) All models were superimposed and the
      "FRankenstein's monster" (FR, fold recognition) model was built from best-scoring
      segments. The final model was obtained after limited energy minimization to
      remove steric clashes between sidechains from different fragments. The novelty of
      this approach is in the focus on "vertical" recombination of structure fragments,
      typical for the ab initio field, rather than "horizontal" sequence alignment
      typical for comparative modeling. We tested the usefulness of the "FRankenstein"
      approach for non-expert predictors: only the leader of our team had considerable
      experience in protein modeling - he registered as a separate group (020) and
      submitted models built only by himself. At the onset of CASP5, the other five
      members of the team (students) had very little or no experience with modeling.
      They followed the same protocol in a deliberately naive way. In the fourth step
      they used solely the VERIFY3D criterion to compare their models and the leader's
      model (the latter regarded only as one of the many alternatives) and generated
      the hybrid or selected only one model for submission (group 517). In order to
      compare our protocol with the traditional "one target-one template-one alignment"
      approach, we submitted (as a separate group 242) models selected from those
      automatically generated by all CAFASP servers (i.e. obtained without any human
      intervention). Here, we compare the results obtained by the three "groups",
      describe successes and failures of the "FRankenstein" approach and discuss future
      developments of comparative modeling. The automatic version of our multi-step
      protocol is being developed as a meta-server; the prototype is freely available
      at http://genesilico.pl/meta/.

PMID- 14579326
TI  - Comparative modeling in CASP5: progress is evident, but alignment errors remain a
      significant hindrance.
AB  - Models for 20 comparative modeling targets were submitted for the fifth round of
      the "blind" test of protein structure prediction methods (CASP5;
      http://predictioncenter.llnl.gov/casp5). The modeling approach used in CASP5 was
      similar to that used 2 years ago in CASP4 (Venclovas, Proteins 2001; Suppl 5:47
      54). The main features of this approach include use of multiple templates,
      initial assessment of alignment reliability in a region-specific manner, and
      structure-based selection of alignment variants in unreliable regions. The CASP5
      modeling results presented here show significant improvement in comparison to
      CASP4, especially in the area of distant homology. The improvements include more
      effective use of multiple templates and better alignments. However, a number of
      structurally conserved regions in submitted distant homology models were
      misaligned. Analysis of these errors indicates that the absolute majority of them
      occurred in regions deemed unreliable in the course of model building. Most of
      these error-prone regions can be characterized by their peripheral location and a
      lack of conserved sequence patterns. For a few of the error-prone regions, all
      methods evaluated during CASP5 proved ineffective, pointing to the need for more
      sensitive energy-based methods. Despite these remaining issues, the applicability
      of comparative modeling continues to expand into more distant evolutionary
      relationships, providing a means to structurally characterize a significant
      number of currently available protein sequences.

PMID- 14579327
TI  - Modeling three-dimensional protein structures for CASP5 using the 3D-SHOTGUN meta
      predictors.
AB  - Full-atom models were generated for all CASP5 targets by using the fully
      automated 3D-SHOTGUN fold recognition meta-predictors (Fischer D, Proteins
      2003;51:434-441). The 3D-SHOTGUN meta-predictors assemble hybrid 3D models by
      combining structural information of a number of independently generated, fold
      recognition models. At the time CASP5 took place, the 3D-SHOTGUN servers
      generated unrefined C(alpha)-only models. Fischer's participation in CASP had
      three main goals. The first was to test the value of using 3D-SHOTGUN models as
      input to a refinement procedure. The second goal was to test whether human
      intervention could result in a better performance than that of the automated
      servers. The third goal was to evaluate which human procedures, not yet
      implemented within the 3D-SHOTGUN servers, can be implemented in the future. For
      CASP5, our group's predictions applied a very simple approach using the multiple
      parent option of the Modeller program (Sali and Blundell, J Mol Biol 1993;234:779
      815). The input to Modeller was different combinations of the unrefined 3D
      SHOTGUN models and the sequence-template alignments used by 3D-SHOTGUN's assembly
      step. Our evaluation of the accuracies of the refined versus the SHOTGUN models
      shows that the refined models were consistently slightly more accurate than
      SHOTGUN's. For a few targets, the manual use of the information from the CAFASP
      servers resulted in better human models. This manual intervention was
      particularly valuable in the identification of domains, still a difficult feature
      for automated servers. The CASP5 results indicate that 3D-SHOTGUN's hybrid models
      can be a valuable starting point for full-atom refinement and that the resulting
      refined models are, on average, more accurate than those produced by the servers.
      Thus, we conclude that our three goals were achieved. A preliminary automated
      version of the refinement procedure, named SHGUM, is now available.

PMID- 14579328
TI  - CASP5 assessment of fold recognition target predictions.
AB  - We present an overview of the fifth round of Critical Assessment of Protein
      Structure Prediction (CASP5) fold recognition category. Prediction models were
      evaluated by using six different structural measures and four different alignment
      measures, and these scores were compared to those assigned manually over a
      diverse subset of target domains. Scores were combined to compare overall
      performance of participating groups and to estimate rank significance. The
      methods used by a few groups outperformed all other methods in terms of the
      evaluated criteria and could be considered state-of-the-art in structure
      prediction. We discuss a few examples of difficult fold recognition targets to
      highlight the progress of ab initio-type methods on difficult structure analogs
      and the difficulties of predicting multidomain targets and selecting prediction
      models. We also compared the results of manual groups to those of automatic
      servers evaluated in parallel by CAFASP, showing that the top performing
      automated server structure predictions approached those of the best manual
      predictors.

PMID- 14579329
TI  - Protein structure prediction of CASP5 comparative modeling and fold recognition
      targets using consensus alignment approach and 3D assessment.
AB  - For the fifth round of Critical Assessment of Techniques for Protein Structure
      Prediction (CASP5) all comparative modeling (CM) and fold recognition (FR) target
      proteins were modeled using a combination of consensus alignment strategy and 3D
      assessment. A large number and broad variety of prediction targets, with sequence
      identity between each modeled domain and the related known structure, ranging
      from 6 to 49%, represented all difficulty levels in comparative modeling and fold
      recognition. The critical steps in modeling, selection of template(s) and
      generation of sequence-to-structure alignment, were based on the results of
      secondary structure prediction and tertiary fold recognition carried out using
      the Meta Server coupled with the 3D-Jury system. The main idea behind the
      modeling procedure was to select the most common alignment variants provided by
      individual servers, as well as to generate several alternatives for questionable
      regions and to evaluate them in 3D by building corresponding molecular models.
      Analysis of fold-specific features and sequence conservation patterns for the
      target family was also widely used at this stage. For both CM and FR targets
      remote homologs of known structure were clearly recognized by the 3D-Jury system.
      In the analogous fold recognition subcategory, the correct fold was identified
      for five out of eight domains. The average alignment accuracy for FR models (48%)
      was far less than for CM predictions (80%). These finding, coupled with the
      observation that in the majority of cases the submitted models were not closer to
      the experimental structure than their best templates, indicate that, especially
      for difficult targets, there is still ample room for improvement.

PMID- 14579330
TI  - Application of 3D-Jury, GRDB, and Verify3D in fold recognition.
AB  - In CASP5, the BioInfo.PL group has used the structure prediction Meta Server and
      the associated newly developed flexible meta-predictor, called 3D-Jury, as the
      main structure prediction tools. The most important feature of the meta-predictor
      is a high (86%) correlation between the reported confidence score and the quality
      of the selected model. The Gene Relational Database (GRDB) was used to confirm
      the fold recognition results by selecting distant homologues and subsequent
      structure prediction with the Meta Server. A fragment-splicing procedure was
      performed as a final processing step with large fragments extracted from selected
      models using model quality control provided by Verify3D. The comparison of
      submitted models with the native structure conducted after the CASP meeting
      showed that the GRDB-supported structure prediction led to a satisfactory
      template fold selection, whereas the fragment-splicing procedure must be improved
      in the future.

PMID- 14579331
TI  - Novel use of a genetic algorithm for protein structure prediction: searching
      template and sequence alignment space.
AB  - A novel genetic algorithm was applied to all CASP5 targets. The algorithm
      simultaneously searches template and alignment space. Results show that the
      current implementation of the method is perhaps most useful in recognizing and
      refining remote homology targets. This new method is briefly described and
      results are analyzed. Strengths and weaknesses of the current implementation of
      the algorithm are discussed.

PMID- 14579332
TI  - Using multiple structure alignments, fast model building, and energetic analysis
      in fold recognition and homology modeling.
AB  - We participated in the fold recognition and homology sections of CASP5 using
      primarily in-house software. The central feature of our structure prediction
      strategy involved the ability to generate good sequence-to-structure alignments
      and to quickly transform them into models that could be evaluated both with
      energy-based methods and manually. The in-house tools we used include: a) HMAP
      (Hybrid Multidimensional Alignment Profile)-a profile-to-profile alignment method
      that is derived from sequence-enhanced multiple structure alignments in core
      regions, and sequence motifs in non-structurally conserved regions. b) NEST-a
      fast model building program that applies an "artificial evolution" algorithm to
      construct a model from a given template and alignment. c) GRASP2-a new structure
      and alignment visualization program incorporating multiple structure
      superposition and domain database scanning modules. These methods were combined
      with model evaluation based on all atom and simplified physical-chemical energy
      functions. All of these methods were under development during CASP5 and
      consequently a great deal of manual analysis was carried out at each stage of the
      prediction process. This interactive model building procedure has several
      advantages and suggests important ways in which our and other methods can be
      improved, examples of which are provided.

PMID- 14579333
TI  - Predictions without templates: new folds, secondary structure, and contacts in
      CASP5.
AB  - We present the assessment of CASP5 predictions in the new fold category. For
      coordinate predictions, we considered five targets with new folds and eight lying
      on the fold recognition borderline. We performed detailed visual and numerical
      comparisons between predicted and experimental structures to assess prediction
      accuracy. The two procedures largely agreed, but the visual inspection identified
      instances where metrics, such as GDT_TS, ranked what we considered incorrect
      predictions highly. We found the quality of the best predictions to be very good:
      for nearly every target at least one group predicted a structure close to the
      correct one. However, selection of the best of five models is still problematic.
      The group of David Baker once again proved to be best overall, with many
      individual highlights. However, high quality and consistency were also seen from
      others, suggesting that the community is moving toward general procedures to
      predict accurate structures for proteins showing no resemblance to anything seen
      before. Predictions for secondary structure showed at best limited progress since
      CASP4. The number of targets is probably too small to spot differences in
      performance between methods, suggesting that such predictions might be better
      evaluated with schemes involving more proteins. For contact predictions,
      accuracies are still low, although there were several instances of accurate and
      useful contacts predicted de novo, and new approaches hint at future progress.

PMID- 14579334
TI  - Rosetta predictions in CASP5: successes, failures, and prospects for complete
      automation.
AB  - We describe predictions of the structures of CASP5 targets using Rosetta. The
      Rosetta fragment insertion protocol was used to generate models for entire target
      domains without detectable sequence similarity to a protein of known structure
      and to build long loop insertions (and N-and C-terminal extensions) in cases
      where a structural template was available. Encouraging results were obtained both
      for the de novo predictions and for the long loop insertions; we describe here
      the successes as well as the failures in the context of current efforts to
      improve the Rosetta method. In particular, de novo predictions failed for large
      proteins that were incorrectly parsed into domains and for topologically complex
      (high contact order) proteins with swapping of segments between domains. However,
      for the remaining targets, at least one of the five submitted models had a long
      fragment with significant similarity to the native structure. A fully automated
      version of the CASP5 protocol produced results that were comparable to the human
      assisted predictions for most of the targets, suggesting that automated genomic
      scale, de novo protein structure prediction may soon be worthwhile. For the three
      targets where the human-assisted predictions were significantly closer to the
      native structure, we identify the steps that remain to be automated.

PMID- 14579335
TI  - TOUCHSTONE: a unified approach to protein structure prediction.
AB  - We have applied the TOUCHSTONE structure prediction algorithm that spans the
      range from homology modeling to ab initio folding to all protein targets in
      CASP5. Using our threading algorithm PROSPECTOR that does not utilize input from
      metaservers, one threads against a representative set of PDB templates. If a
      template is significantly hit, Generalized Comparative Modeling designed to span
      the range from closely to distantly related proteins from the template is done.
      This involves freezing the aligned regions and relaxing the remaining structure
      to accommodate insertions or deletions with respect to the template. For all
      targets, consensus predicted side chain contacts from at least weakly threading
      templates are pooled and incorporated into ab initio folding. Often, TOUCHSTONE
      performs well in the CM to FR categories, with PROSPECTOR showing significant
      ability to identify analogous templates. When ab initio folding is done,
      frequently the best models are closer to the native state than the initial
      template. Among the particularly good predictions are T0130 in the CM/FR
      category, T0138 in the FR(H) category, T0135 in the FR(A) category, T0170 in the
      FR/NF category and T0181 in the NF category. Improvements in the approach are
      needed in the FR/NF and NF categories. Nevertheless, TOUCHSTONE was one of the
      best performing algorithms over all categories in CASP5.

PMID- 14579336
TI  - Assembling novel protein folds from super-secondary structural fragments.
AB  - The results of applying a fragment-based protein tertiary structure prediction
      method to the prediction of 14 CASP5 target domains are described. The method is
      based on the assembly of supersecondary structural fragments taken from highly
      resolved protein structures using a simulated annealing algorithm. A number of
      good predictions for proteins with novel folds were produced, although not always
      as the first model. For two fold recognition targets, FRAGFOLD produced the most
      accurate model in both cases, despite the fact that the predictions were not
      based on a template structure. Although clear progress has been made in improving
      FRAGFOLD since CASP4, the ranking of final models still seems to be the main
      problem that needs to be addressed before the next CASP experiment.

PMID- 14579337
TI  - Prediction of protein structure by emphasizing local side-chain/backbone
      interactions in ensembles of turn fragments.
AB  - The prediction strategy used in the CASP5 experiment was premised on the
      assumption that local side-chain/backbone interactions are the principal
      determinants of protein structure at low resolution. Our implementation of this
      assumption made extensive use of a scoring function based on the propensities of
      the 20 amino acids for 137 different sub-regions of the Ramachandran plot,
      allowing estimation of the quality of fit between a sequence segment and a known
      conformation. New folds were predicted in three steps: prediction of secondary
      structure, threading to isolate fragments of protein structures corresponding to
      one turn plus flanking helices/strands, and recombination of overlapping
      fragments. The most important step in this fragment ensemble approach, the
      isolation of turn fragments, employed 2 to 6 sequence homologues when available,
      with clustering of the best scoring fragments to recover the most common turn
      arrangement. Recombinants formed between 3 to 8 turn fragments, with cross-overs
      confined to helix/strand segments, were selected for compactness plus low energy
      as estimated by empirical amino acid pair potentials, and the most common overall
      topology identified by visual inspection. Because significant amounts of steric
      overlap were permitted during the recombination step, the final model was
      manually adjusted to reduce overlap and to enhance protein-like structural
      features. Even though only one or two models were submitted per target, for
      several targets the correct chain topology was predicted for fragment lengths up
      to 100 amino acids.

PMID- 14579338
TI  - Combining local-structure, fold-recognition, and new fold methods for protein
      structure prediction.
AB  - This article presents an overview of the SAM-T02 method for protein fold
      recognition and the UNDERTAKER program for ab initio predictions. The SAM-T02
      server is an automatic method that uses two-track hidden Markov models (HMMS) to
      find and align template proteins from PDB to the target protein. The two-track
      HMMs use an amino acid alphabet and one of several different local structure
      alphabets. The UNDERTAKER program is a new fragment-packing program that can use
      short or long fragments and alignments to create protein conformations. The HMMs
      and fold-recognition alignments from the SAM-T02 method were used to generate the
      fragment and alignment libraries used by UNDERTAKER. We present results on a few
      selected targets for which this combined method worked particularly well: T0129,
      T0181, T0135, T0130, and T0139.

PMID- 14579339
TI  - Predicting interresidue contacts using templates and pathways.
AB  - We present a novel method, HMMSTR-CM, for protein contact map predictions.
      Contact potentials were calculated by using HMMSTR, a hidden Markov model for
      local sequence structure correlations. Targets were aligned against protein
      templates using a Bayesian method, and contact maps were generated by using these
      alignments. Contact potentials then were used to evaluate these templates. An ab
      initio method based on the target contact potentials using a rule-based strategy
      to model the protein-folding pathway was developed. Fold recognition and ab
      initio methods were combined to produce accurate, protein-like contact maps.
      Pathways sometimes led to an unambiguous prediction of topology, even without
      using templates. The results on CASP5 targets are discussed. Also included is a
      brief update on the quality of fully automated ab initio predictions using the I
      sites server.

PMID- 14579340
TI  - CAFASP3: the third critical assessment of fully automated structure prediction
      methods.
AB  - We present the results of the fully automated CAFASP3 experiment, which was
      carried out in parallel with CASP5, using the same set of prediction targets.
      CAFASP participation is restricted to fully automatic structure prediction
      servers. The servers' performance is evaluated by using previously announced,
      objective, reproducible and fully automated evaluation methods. More than 60
      servers participated in CAFASP3, covering all categories of structure prediction.
      As in the previous CAFASP2 experiment, it was possible to identify a group of 5
      10 top performing independent servers. This group of top performing independent
      servers produced relatively accurate models for all the 32 "Homology Modeling"
      targets, and for up to 43% of the 30 "Fold Recognition" targets. One of the most
      important results of CAFASP3 was the realization of the value of all the
      independent servers as a group, as evidenced by the superior performance of "meta
      predictors" (defined here as predictors that make use of the output of other
      CAFASP servers). The performance of the best automated meta-predictors was
      roughly 30% higher than that of the best independent server. More significantly,
      the performance of the best automated meta-predictors was comparable with that of
      the best 5-10 human CASP predictors. This result shows that significant progress
      has been achieved in automatic structure prediction and has important
      implications to the prospects of automated structure modeling in the context of
      structural genomics.

PMID- 14579341
TI  - 3DS3 and 3DS5 3D-SHOTGUN meta-predictors in CAFASP3.
AB  - The performance of the 3DS3 and 3DS5 3D-SHOTGUN meta-predictors in CAFASP3 is
      reported. The 3D-SHOTGUN meta-predictors are fully automatic fold recognition
      servers that attempt to incorporate into the prediction process a number of
      successful strategies that human predictors often apply. Namely, the input to 3D
      SHOTGUN are the top five models predicted by a number of independent fold
      recognition servers and its output are hybrid models, assembled by using the
      recurrent structural information from the input models. The resulting hybrid
      models are, on average, more accurate and more complete than the input models.
      When evaluated on a large set of prediction targets, the 3D-SHOTGUN servers show
      increased sensitivities and significantly better specificities. For CAFASP3, the
      3DS3 and 3DS3 and 3DS5 used a preliminary implementation of the 3D-SHOTGUN
      method, which lacked a refinement step. Although this did not have a significant
      effect on the easier targets, for the hardest prediction targets, where the input
      models had significant structural conflicts, the 3D-SHOTGUN models contained a
      number of non-native-like features such as fragmentation and overlaps. The
      CAFASP3 evaluation identified the 3D-SHOTGUN meta-predictors within the top three
      most sensitive and most specific servers. A fully automated refinement step to
      the 3D-SHOTGUN method is currently being implemented, and preliminary results
      indicate that in addition to "cleaning up" such undesirable features, it is able
      to further increase the accuracy of the resulting models.

PMID- 14579342
TI  - Automated prediction of CASP-5 structures using the Robetta server.
AB  - Robetta is a fully automated protein structure prediction server that uses the
      Rosetta fragment-insertion method. It combines template-based and de novo
      structure prediction methods in an attempt to produce high quality models that
      cover every residue of a submitted sequence. The first step in the procedure is
      the automatic detection of the locations of domains and selection of the
      appropriate modeling protocol for each domain. For domains matched to a homolog
      with an experimentally characterized structure by PSI-BLAST or Pcons2, Robetta
      uses a new alignment method, called K*Sync, to align the query sequence onto the
      parent structure. It then models the variable regions by allowing them to explore
      conformational space with fragments in fashion similar to the de novo protocol,
      but in the context of the template. When no structural homolog is available,
      domains are modeled with the Rosetta de novo protocol, which allows the full
      length of the domain to explore conformational space via fragment-insertion,
      producing a large decoy ensemble from which the final models are selected. The
      Robetta server produced quite reasonable predictions for targets in the recent
      CASP-5 and CAFASP-3 experiments, some of which were at the level of the best
      human predictions.

PMID- 14579343
TI  - Automatic consensus-based fold recognition using Pcons, ProQ, and Pmodeller.
AB  - CASP provides a unique opportunity to compare the performance of automatic fold
      recognition methods with the performance of manual experts who might use these
      methods. Here, we show that a novel automatic fold recognition server, Pmodeller,
      is getting close to the performance of manual experts. Although a small group of
      experts still perform better, most of the experts participating in CASP5 actually
      performed worse even though they had full access to all automatic predictions.
      Pmodeller is based on Pcons (Lundstrom et al., Protein Sci 2001; 10(11):2354
      2365) the first "consensus" predictor that uses predictions from many other
      servers. Therefore, the success of Pmodeller and other consensus servers should
      be seen as a tribute to the collective of all developers of fold recognition
      servers. Furthermore we show that the inclusion of another novel method, ProQ2,
      to evaluate the quality of the protein models improves the predictions.

PMID- 14579344
TI  - LiveBench-6: large-scale automated evaluation of protein structure prediction
      servers.
AB  - The aim of the LiveBench experiment is to provide a continuous evaluation of
      structure prediction servers in order to inform potential users about the current
      state-of-the-art structure prediction tools and in order to help the developers
      to analyze and improve the services. This round of the experiment was conducted
      in parallel to the blind CAFASP-3 evaluation experiment. The data collected
      almost simultaneously enables the comparison of servers on two different
      benchmark sets. The number of servers has doubled from the last evaluated
      LiveBench-4 experiment completed in April 2002, just before the beginning of
      CAFASP-3. This can be partially attributed to the rapid development in the area
      of meta-predictors (consensus servers). The current results confirm the high
      sensitivity and specificity of the meta-predictors. Nevertheless, the comparison
      between the autonomous (not meta) servers participating in the last CAFASP-2 and
      LiveBench-2 experiment and the current set of autonomous servers demonstrates
      that progress has been made also in sequence structure fitting functions. In
      addition to the growing number of participants, the current experiment marks the
      introduction of new evaluation procedures, which are aimed to correlate better
      with functional characteristics of models.

PMID- 14579345
TI  - CAFASP3 in the spotlight of EVA.
AB  - We have analysed fold recognition, secondary structure and contact prediction
      servers from CAFASP3. This assessment was carried out in the framework of the
      fully automated, web-based evaluation server EVA. Detailed results are available
      at http://cubic.bioc.columbia.edu/eva/cafasp3/. We observed that the sequence
      unique targets from CAFASP3/CASP5 were not fully representative for evaluating
      performance. For all three categories, we showed how careless ranking might be
      misleading. We compared methods from all categories to experts in secondary
      structure and contact prediction and homology modellers to fold recognisers.
      While the secondary structure experts clearly outperformed all others, the
      contact experts appeared to outperform only novel fold methods. Automatic
      evaluation servers are good at getting statistics right and at using these to
      discard misleading ranking schemes. We challenge that to let machines rule where
      they are best might be the best way for the community to enjoy the tremendous
      benefit of CASP as a unique opportunity for brainstorming.

PMID- 14579346
TI  - Evaluation of disorder predictions in CASP5.
AB  - This paper reports an analysis of the accuracy of predictions of structural
      disorder received as part of the CASP5 experiment. Six groups made predictions of
      disorder. The predictions of the four most active groups have been compared with
      the experimental results, in terms of the sensitivity and specificity of the
      methods. All four methods succeed in detecting over half the disordered residues
      in the targets, with a generally low rate of over-prediction. Two of the methods
      perform significantly better when the structure of a related protein is
      available. There is a trade-off between the fraction of disordered residues
      detected and the extent of over-prediction, and groups have adopted different
      compromises in this respect. Comparison of performance at the same over
      prediction rates highlights the role of related structures in some methods rather
      than others, with different groups achieving the highest sensitivity for
      different target sets. Over-all, the methods are clearly of considerable use in
      identifying potential disorder.

PMID- 14579348
TI  - Prediction of disordered regions in proteins from position specific score
      matrices.
AB  - We describe here the results of using a neural network based method (DISOPRED)
      for predicting disordered regions in 55 proteins in the 5(th) CASP experiment. A
      set of 715 highly resolved proteins with regions of disorder was used to train
      the network. The inputs to the network were derived from sequence profiles
      generated by PSI-BLAST. A post-filter was applied to the output of the network to
      prevent regions being predicted as disordered in regions of confidently predicted
      alpha helix or beta sheet structure. The overall two-state prediction accuracy
      for the method is very high (90%) but this is highly skewed by the fact that most
      residues are observed to be ordered. The overall Matthews' correlation
      coefficient for the submitted predictions is 0.34, which gives a more realistic
      impression of the overall accuracy of the method, though still indicates
      significant predictive power.

PMID- 14579347
TI  - Predicting intrinsic disorder from amino acid sequence.
AB  - Blind predictions of intrinsic order and disorder were made on 42 proteins
      subsequently revealed to contain 9,044 ordered residues, 284 disordered residues
      in 26 segments of length 30 residues or less, and 281 disordered residues in 2
      disordered segments of length greater than 30 residues. The accuracies of the six
      predictors used in this experiment ranged from 77% to 91% for the ordered regions
      and from 56% to 78% for the disordered segments. The average of the order and
      disorder predictions ranged from 73% to 77%. The prediction of disorder in the
      shorter segments was poor, from 25% to 66% correct, while the prediction of
      disorder in the longer segments was better, from 75% to 95% correct. Four of the
      predictors were composed of ensembles of neural networks. This enabled them to
      deal more efficiently with the large asymmetry in the training data through
      diversified sampling from the significantly larger ordered set and achieve better
      accuracy on ordered and long disordered regions. The exclusive use of long
      disordered regions for predictor training likely contributed to the disparity of
      the predictions on long versus short disordered regions, while averaging the
      output values over 61-residue windows to eliminate short predictions of order or
      disorder probably contributed to the even greater disparity for three of the
      predictors. This experiment supports the predictability of intrinsic disorder
      from amino acid sequence.

PMID- 14579349
TI  - Assessment of RAPTOR's linear programming approach in CAFASP3.
AB  - We have developed a new algorithm based on the mathematical theory of linear
      programming (LP) and implemented it in our program RAPTOR. Our new approach
      provides an elegant formulation of the protein-threading problem, overcomes the
      intractability problem of protein threading, in practice, and allows us to use
      existing powerful linear programming software to obtain optimal protein threading
      solutions. CASP5 and CAFASP3 gave us the first chance to test RAPTOR in an
      unbiased way. RAPTOR was ranked as the top individual (automatic) server for fold
      recognition by the CAFASP3 organizers. In this short article, we describe
      RAPTOR's LP formulation, assess RAPTOR's performance in CAFASP3/CASP5, explain
      why it has superceded other existing automatic individual methods, and point out
      its strengths, limitations, extensions, and prospects for improvement.

PMID- 14579350
TI  - Assessment of progress over the CASP experiments.
AB  - The quality of structure models produced in the CASP5 experiment has been
      compared with that in earlier CASPs. The most significant progress is in the fold
      recognition regime, where the development of meta-servers has allowed more
      accurate consensus models to be generated. In contrast to this, there is little
      evidence of progress in producing more accurate comparative models, particularly
      those based on sequence identities > 30%. For comparative models based on low
      sequence identity and for fold recognition models, accuracy depends primarily on
      the fraction of the target structure that is similar to an available template,
      and the quality of the alignment. Overall, these results indicate that there are
      still no effective methods of improving model quality beyond that obtained by
      successfully copying a template structure. For models of proteins with previously
      unknown folds, there appears to be a pause in the previous consistent
      improvement. There is some evidence that more groups are producing top-quality
      models, however. Although specific progress between successive experiments is
      sometimes difficulty to identify, over the history of all the CASPs there has
      been steady, if sometimes slow, progress in all modeling regimes.

PMID- 14579351
TI  - Unfolding of the cold shock protein studied with biased molecular dynamics.
AB  - The cold shock protein from Bacillus caldolyticus is a small beta-barrel protein
      that folds in a two-state mechanism. For the native protein and for several
      mutants, a wealth of experimental data are available on stability and folding, so
      that it is an optimal system to study this process. We compare data from
      unfolding simulations (trajectories of 5 and up to 12 ns) obtained with a bias
      potential at room temperature and from unbiased thermal unfolding simulations
      with experimental data. The unfolding patterns derived from the trajectories
      starting from different native-like conformations and subject to different
      unfolding conditions agree. The transition state found in the simulations of
      unfolding is close to the native structure in agreement with experiment.
      Moreover, a lower value of the free energy barrier of unfolding was found for the
      mutant R3E than for the mutant E46A and the native protein, as indicated by
      experimental data. The first unfolding event involves the three-stranded beta
      sheet whose decomposition corresponds to the transition state. In contrast to
      conclusions drawn from experiments, we found that the two-stranded beta-strand
      forms the most stable substructure, which decomposes very late in the unfolding
      process. However, assuming that this structure forms very early in the folding
      process, our findings would not contradict the experiments but require a
      different interpretation of them.

PMID- 14579352
TI  - Fluorescent dyes as probes to study lipid-binding proteins.
AB  - We studied the equilibrium binding of two hydrophobic fluorescent dyes, ANS and
      bisANS, to four members of a family of intracellular lipid-binding proteins:
      IFABP, CRABP I, CRABP II, and ILBP. The spectral and binding parameters for the
      probes bound to the proteins were determined. Typically, there was a single
      binding site on each protein for the ligands. However, IFABP cooperatively bound
      a second bisANS molecule in the binding pocket. Comparative analysis of
      affinities and spectral characteristics for the two probes allowed us to examine
      the contributions of electrostatic and hydrophobic interactions to the binding
      process, and to address some aspects of the internal structure of the studied
      proteins.

PMID- 14579353
TI  - Importance of sequence specificity for predicting protein folding pathways:
      perturbed Gaussian chain model.
AB  - Recent experimental and theoretical studies suggest that rates and pathways of
      protein folding are largely decided by topology of the native structures, at
      least for small proteins. However, some exceptions are known; for example,
      protein L and protein G have the same topology, but exhibit different
      characteristics of the TSE. Thus, folding pathways of some proteins are
      critically affected by detailed information on amino acid sequences. To
      investigate the sequence specificity, we calculate folding pathways of 20 small
      proteins using the perturbed Gaussian chain model developed by Portman et al.
      (Phys Rev Lett 1998;81:5237-5240; J Chem Phys 2001;114:5069-5081).
      Characteristics of the TSE predicted by the model are in good agreement with
      experimental phi-value data for many proteins at coarse-grained level.
      Especially, estimation of folding TSE for protein G and protein L based on both
      topology and additional sequence information are consistent with experimental phi
      value data. With only topology information, however, the model predicts the TSE
      of protein G incorrectly. Moreover, the model that uses topology and sequence
      information describes free energy profiles of two-state and three-state folders
      consistently with experiment, whereas the topology only model predicts free
      energy profiles of some proteins incorrectly. This indicates that sequence
      specificity also has critical roles in determining the folding pathways for some
      proteins.

PMID- 14579354
TI  - Atomic contact vectors in protein-protein recognition.
AB  - The ability to analyze and compare protein-protein interactions on the structural
      level is critical to our understanding of various aspects of molecular
      recognition and the functional interplay of components of biochemical networks.
      In this study, we introduce atomic contact vectors (ACVs) as an intuitive way to
      represent the physico-chemical characteristics of a protein-protein interface as
      well as a way to compare interfaces to each other. We test the utility of ACVs in
      classification by using them to distinguish between homodimers and crystal
      contacts. Our results compare favorably with those reported by other authors. We
      then apply ACVs to mine the PDB for all known protein-protein complexes and
      separate transient recognition complexes from permanent oligomeric ones. Getting
      at the basis of this difference is important for our understanding of recognition
      and we achieved a success rate of 91% for distinguishing these two classes of
      complexes. Although accessible surface area of the interface is a major
      discriminating feature, we also show that there are distinct differences in the
      contact preferences between the two kinds of complexes. Illustrating the
      superiority of ACVs as a basic comparison measure over a sequence-based approach,
      we derive a general rule of thumb to determine whether two protein-protein
      interfaces are redundant. With this method, we arrive at a nonredundant set of
      209 recognition complexes--the largest set reported so far.

PMID- 14579355
TI  - The tissue factor/factor VIIa/factor Xa complex: a model built by docking and
      site-directed mutagenesis.
AB  - Factor X is activated to factor Xa (fXa) in the extrinsic coagulation pathway by
      the tissue factor (TF)/factor VIIa (fVIIa) complex. Upon activation, the fXa
      molecule remains associated with the TF/fVIIa complex, and this ternary complex
      is known to activate protease-activated receptors (PARs) 1 and 2. Activation of
      fVII in the TF complex by fXa is also seen at physiologic concentrations. The
      ternary complexes TF/fVII/fXa, TF/fVIIa/fX, and TF/fVIIa/fXa are therefore all
      physiologically relevant and of interest as targets for inhibition of both
      coagulation and cell-signaling pathways that are important in cardiovascular
      disease and inflammation. We therefore present a model of the TF/fVIIa/fXa
      complex, built with the use of the available structures of the TF/fVIIa complex
      and fXa by protein-protein docking calculations with the program Surfdock. The
      fXa model has an extended conformation, similar to that of fVIIa in the TF/fVIIa
      complex, with extensive interactions with TF and the protease domain of fVIIa.
      All four domains of fXa are involved in the interaction. The gamma
      carboxyglutamate (Gla) and epithelial growth factor (EGF1 and EGF2) domains of
      fVIIa are not significantly involved in the interaction. Docking of the Gla
      domain of fXa to TF/fVIIa has been reported previously. The docking results
      identify potential interface residues, allowing rational selection of target
      residues for site-directed mutagenesis. This combination of docking and
      mutagenesis confirms that residues Glu51 and Asn57 in the EGF1 domain, Asp92 and
      Asp95 in the EGF2 domain, and Asp 185a, Lys 186, and Lys134 in the protease
      domain of factor Xa are involved in the interaction with TF/fVIIa. Other fX
      protease domain residues predicted to be involved in the interaction come from
      the 160s loop and the N-terminus of the fX protease domain, which is oriented in
      such a way that activation of both fVII by fXa, and the reciprocal fX activation
      by fVIIa, is possible.

PMID- 14579356
TI  - A second binding site revealed by C-terminal truncation of calpain small subunit,
      a penta-EF-hand protein.
AB  - The subunits in calpain and in the related penta-EF-hand (PEF) proteins are bound
      through contacts between the unpaired EF-hand 5 from each subunit. To study
      subunit binding further, a tetra-EF-hand 18 kDa N- and C-terminally truncated
      form of the calpain small subunit was prepared (18k). This protein does not
      combine with the calpain large subunit to form active calpain, but forms
      homodimers in solution, as shown by ultracentrifugation. The X-ray structure of
      the 18k protein in the presence of cadmium was solved to a resolution of 2.0 A.
      The structure of the monomer is almost identical to the known structure of the
      calpain small subunit, but the 18k protein forms an oligomer in the crystal by
      the use of two binding sites. One of these sites is an artefact arising from the
      C-terminal truncation, but the other is a naturally occurring site that is fully
      exposed to water in intact purified calpain. The characteristics of this site
      suggest that it may be important in binding other protein modulators involved in
      the regulation of calpain and of PEF proteins.

PMID- 14579357
TI  - Accessibility of oxygen with respect to the heme pocket in horseradish
      peroxidase.
AB  - Oxygen and other molecules of similar size take part in a variety of protein
      reactions. Therefore, it is critical to understand how these small molecules
      penetrate the protein matrix. The protein system studied in this case is
      horseradish peroxidase (HRP). We have converted the native HRP into a
      phosphorescent analog by replacing the heme prosthetic group by Pd-mesoporphyrin.
      Oxygen readily quenches the phosphorescence of Pd porphyrins, and this can be
      used to characterize oxygen diffusion through the protein matrix. Our
      measurements indicate that solvent viscosity and pH modulate the accessibility of
      the heme pocket relative to small molecules. The binding of the substrate
      benzohydroxamic acid (BHA) to the protein drastically impedes oxygen access to
      the heme pocket. These results indicate that, first, the penetration of small
      molecules through the protein matrix is a function of protein dynamics, and
      second, there are specific pathways for the diffusion of these molecules. The
      effect of substrate and pH on protein dynamics has been investigated with the use
      of molecular dynamics calculations. We demonstrate that the model of a
      "fluctuating entry point," as suggested by Zwanzig (J Chem Phys 1992;97:3587
      3589), properly describes the diffusion of oxygen through the protein matrix.

PMID- 14579358
TI  - Characterization of the active site of DNA polymerase beta by molecular dynamics
      and quantum chemical calculation.
AB  - It is well established that the fully formed polymerase active site of the DNA
      repair enzyme, polymerase beta (pol beta), including two bound Mg2+ cations and
      the nucleoside triphosphate (dNTP) substrate, exists at only one point in the
      catalytic cycle just prior to the chemical nucleotidyl transfer step. The
      structure of the active conformation has been the subject of much interest as it
      relates to the mechanism of the chemical step and also to the question of
      fidelity assurance. Although crystal structures of ternary pol beta-(primer
      template) DNA-dNTP complexes have provided the main structural features of the
      active site, they are necessarily incomplete due to intentional alterations
      (e.g., removal of the 3'OH groups from primer and substrate) needed to obtain a
      structure from midcycle. Working from the crystal structure closest to the fully
      formed active site [Protein Data Bank (PDB) code: 1bpy], two molecular dynamics
      (MD) simulations of the solvated ternary complex were performed: one with the
      missing 3'OHs restored, via modeling, to the primer and substrate, and the other
      without restoration of the 3'OHs. The results of the simulations, together with
      ab initio optimizations on simplified active-site models, indicate that the
      missing primer 3'OH in the crystal structure is responsible for a significant
      perturbation in the coordination sphere of the catalytic cation and allow us to
      suggest several corrections and additions to the active-site structure as
      observed by crystallography. In addition, the calculations help to resolve
      questions raised regarding the protonation states of coordinating ligands.

PMID- 14579359
TI  - Automatic annotation of protein function based on family identification.
AB  - Although genomes are being sequenced at an impressive rate, the information
      generated tells us little about protein function, which is slow to characterize
      by traditional methods. Automatic protein function annotation based on
      computational methods has alleviated this imbalance. The most powerful current
      approach for inferring the function of new proteins is by studying the
      annotations of their homologues, since their common origin is assumed to be
      reflected in their structure and function. Unfortunately, as proteins evolve they
      acquire new functions, so annotation based on homology must be carried out in the
      context of orthologues or subfamilies. Evolution adds new complications through
      domain shuffling: homology (or orthology) frequently corresponds to domains
      rather than complete proteins. Moreover, the function of a protein may be seen as
      the result of combining the functions of its domains. Additionally, automatic
      annotation has to deal with problems related to the annotations in the databases:
      errors (which are likely to be propagated), inconsistencies, or different degrees
      of function specification. We describe a method that addresses these difficulties
      for the annotation of protein function. Sequence relationships are detected and
      measured to obtain a map of the sequence space, which is searched for
      differentiated groups of proteins (similar to islands on the map), which are
      expected to have a common function and correspond to groups of orthologues or
      subfamilies. This mapmaking is done by applying a clustering algorithm based on
      Normalized cuts in graphs. The domain problem is addressed in a simple way:
      pairwise local alignments are analyzed to determine the extent to which they
      cover the entire sequence lengths of the two proteins. This analysis determines
      both what homologues are preferred for functional inheritance and the level of
      confidence of the annotation. To alleviate the problems associated with database
      annotations, the information on all the homologues that are grouped together with
      the query protein are taken into account to select the most representative
      functional descriptors. This method has been applied for the annotation of the
      genome of Buchnera aphidicola (specific host Baizongia pistaciae). Human
      inspection of the annotations allowed an estimation of accuracy of 94%; the
      different kinds of error that may appear when using this approach are described.
      Results can be accessed at http://www.pdg.cnb.uam.es/funcut.html. The programs
      are available upon request, although installation in other systems may be
      complicated.

PMID- 14579360
TI  - RDOCK: refinement of rigid-body protein docking predictions.
AB  - We present a simple and effective algorithm RDOCK for refining unbound
      predictions generated by a rigid-body docking algorithm ZDOCK, which has been
      developed earlier by our group. The main component of RDOCK is a three-stage
      energy minimization scheme, followed by the evaluation of electrostatic and
      desolvation energies. Ionic side chains are kept neutral in the first two stages
      of minimization, and reverted to their full charge states in the last stage of
      brief minimization. Without side chain conformational search or
      filtering/clustering of resulting structures, RDOCK represents the simplest
      approach toward refining unbound docking predictions. Despite its simplicity,
      RDOCK makes substantial improvement upon the top predictions by ZDOCK with all
      three scoring functions and the improvement is observed across all three
      categories of test cases in a large benchmark of 49 non-redundant unbound test
      cases. RDOCK makes the most powerful combination with ZDOCK2.1, which uses
      pairwise shape complementarity as the scoring function. Collectively, they rank a
      near-native structure as the number-one prediction for 18 test cases (37% of the
      benchmark), and within the top 4 predictions for 24 test cases (49% of the
      benchmark). To various degrees, funnel-like energy landscapes are observed for
      these 24 test cases. To the best of our knowledge, this is the first report of
      binding funnels starting from global searches for a broad range of test cases.
      These results are particularly exciting, given that we have not used any
      biological information that is specific to individual test cases and the whole
      process is entirely automated. Among three categories of test cases, the best
      results are seen for enzyme/inhibitor, with a near-native structure ranked as the
      number-one prediction for 48% test cases, and within the top 10 predictions for
      78% test cases. RDOCK is freely available to academic users at
      http://zlab.bu.edu/ approximately rong/dock.

PMID- 14579361
TI  - Dissecting subunit interfaces in homodimeric proteins.
AB  - The subunit interfaces of 122 homodimers of known three-dimensional structure are
      analyzed and dissected into sets of surface patches by clustering atoms at the
      interface; 70 interfaces are single-patch, the others have up to six patches,
      often contributed by different structural domains. The average interface buries
      1,940 A2 of the surface of each monomer, contains one or two patches burying 600
      1,600 A2, is 65% nonpolar and includes 18 hydrogen bonds. However, the range of
      size and of hydrophobicity is wide among the 122 interfaces. Each interface has a
      core made of residues with atoms buried in the dimer, surrounded by a rim of
      residues with atoms that remain accessible to solvent. The core, which
      constitutes 77% of the interface on average, has an amino acid composition that
      resembles the protein interior except for the presence of arginine residues,
      whereas the rim is more like the protein surface. These properties of the
      interfaces in homodimers, which are permanent assemblies, are compared to those
      of protein-protein complexes where the components associate after they have
      independently folded. On average, subunit interfaces in homodimers are twice
      larger than in complexes, and much less polar due to the large fraction belonging
      to the core, although the amino acid compositions of the cores are similar in the
      two types of interfaces.

PMID- 14579362
TI  - Elucidation of the disulfide-folding pathway of hirudin by a topology-based
      approach.
AB  - A theoretical model for the folding of proteins containing disulfide bonds is
      introduced. The model exploits the knowledge of the native state to favor the
      progressive establishment of native interactions. At variance with traditional
      approaches based on native topology, not all native bonds are treated in the same
      way; in particular, a suitable energy term is introduced to account for the
      special strength of disulfide bonds, as well as their ability to undergo
      intramolecular reshuffling. The model thus possesses the minimal ingredients
      necessary to investigate the much debated issue of whether the refolding process
      occurs through partially structured intermediates with native or non-native
      disulfide bonds. This strategy is applied to a context of particular interest,
      the refolding process of hirudin, a thrombin-specific protease inhibitor, for
      which conflicting folding pathways have been proposed. We show that the only two
      parameters in the model (temperature and disulfide strength) can be tuned to
      reproduce well a set of experimental transitions between species with different
      number of formed disulfides. This model is then used to provide a
      characterization of the folding process and a detailed description of the species
      involved in the rate-limiting step of hirudin refolding.

PMID- 14579363
TI  - Many residues in cytochrome c populate alternative states under equilibrium
      conditions.
AB  - A curved temperature dependence of an amide proton NMR chemical shift indicates
      that it explores discrete alternative conformations at least 1% of the time; that
      is, it accesses conformations that lie within 5 kcal/mol(-1) of the ground state.
      The simulations presented show how curvature varies with the nature of the
      alternative state, and are compared to experimental results. From studies in
      different denaturant concentrations, it is concluded that at least 25% of
      residues in reduced horse cytochrome c, covering most of the protein, with the
      exception of the center of the N- and C-terminal helices, visit alternative
      states under equilibrium conditions. The conformational ensemble of the protein
      therefore has high structural entropy. The density of alternative states is
      particularly high near the heme ligand Met80, which is of interest because both
      redox change and the first identified stage in unfolding are associated with
      change in Met80 ligation. By combining theoretical and experimental approaches,
      it is concluded that the alternative states each comprise approximately five
      residues, have in general less structure than the native state, and are accessed
      independently. They are therefore locally unfolded structures. The locations of
      the alternative states match what is known of the global unfolding pathway of
      cytochrome c, suggesting that they may determine the pathway.

PMID- 14579364
TI  - The importance of explicit chain representation in protein folding models: an
      examination of Ising-like models.
AB  - A class of models that represents a protein chain as a sequence of "folded" and
      "unfolded" residues has recently been used to correlate rates and mechanisms of
      protein folding with the protein native structure. In order to better understand
      the conditions under which these "Ising-like" models apply, we compare results
      from this model to those obtained from an off-lattice model which uses the same
      potential function. We find that Ising-like models by construction impose folding
      via a highly sequential nucleation-condensation mechanism, which in turn leads to
      more rugged energy landscapes, fewer "pathways" to the native state, and in the
      specific case examined here, the cold shock protein A from Escherichia coli, a
      qualitative difference in the most likely order of events in folding.

PMID- 14579365
TI  - Three-dimensional structural location and molecular functional effects of
      missense SNPs in the T cell receptor Vbeta domain.
AB  - The mechanisms by which human single nucleotide polymorphisms (SNPs) influence
      susceptibility to disease are not yet well understood. In a previous study, we
      developed a structure-based model that may be used to identify which missense
      SNPs are neutral and which are deleterious to protein function and so potentially
      involved in disease (Wang and Moult, Hum Mutat 2001;263-270). The model has now
      been applied to a set of 54 missense cSNPs in the 46 functional T-cell receptor
      Vbeta-genes. Most of these missense cSNPs are found to be neutral, but 10 are
      identified as likely deleterious to protein function. Only one was previously
      associated with disease. We suggest that the others may be disease related but
      that redundancy in the T-cell response prevents any simple, monogenic effect.
      Therefore, these SNPs are the most likely contributors to complex, polygenic
      disease traits. It has been noted that there is a surprisingly high (74%)
      fraction of nonsynonymous SNPs in these genes. Contrary to expectation, the
      analysis shows that these are not associated with an unusually high fraction of
      deleterious SNPs, nor do they significantly contribute to a larger range of
      antigen recognition or a reduced superantigen-binding repertoire.

PMID- 14579366
TI  - The intracellular domain of the Drosophila cholinesterase-like neural adhesion
      protein, gliotactin, is natively unfolded.
AB  - Drosophila gliotactin (Gli) is a 109-kDa transmembrane, cholinesterase-like
      adhesion molecule (CLAM), expressed in peripheral glia, that is crucial for
      formation of the blood-nerve barrier. The intracellular portion (Gli-cyt) was
      cloned and expressed in the cytosolic fraction of Escherichia coli BLR(DE3) at 45
      mg/L and purified by Ni-NTA (nitrilotriacetic acid) chromatography. Although
      migration on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS
      PAGE), under denaturing conditions, was unusually slow, molecular weight
      determination by matrix-assisted laser desorption/ionization time-of-flight
      (MALDI-TOF) mass spectrometry (MS) confirmed that the product was consistent with
      its theoretical size. Gel filtration chromatography yielded an anomalously large
      Stokes radius, suggesting a fully unfolded conformation. Circular dichroism (CD)
      spectroscopy demonstrated that Gli-cyt was >50% unfolded, further suggesting a
      nonglobular conformation. Finally, 1D-(1)H NMR conclusively demonstrated that Gli
      cyt possesses an extended unfolded structure. In addition, Gli-cyt was shown to
      possess charge and hydrophobic properties characteristic of natively unfolded
      proteins (i.e., proteins that, when purified, are intrinsically disordered under
      physiologic conditions in vitro).

PMID- 14579367
TI  - Crystal structure of a hypothetical protein, TT1725, from Thermus thermophilus
      HB8 at 1.7 A resolution.

PMID- 14579368
TI  - Crystal structure of UDP-N-acetylglucosamine acyltransferase from Helicobacter
      pylori.

PMID- 14579369
TI  - Zebrafish as a model system. Perspective.

PMID- 14579370
TI  - Expression and phylogenetic analyses of three zebrafish FoxI class genes.
AB  - We have identified three novel members of the zebrafish forkhead class I gene
      family, which we have named foxi2, foxi3a, and foxi3b. We have reported
      previously the identification of zebrafish foxi1, which is required for otic
      placode and jaw development. Expression analysis shows that foxi2 is expressed
      within the chordamesoderm during early somitogenesis and the retina and
      pharyngeal arches during later stages. The foxi3a and foxi3b genes likely
      represent a recently duplicated pair, and they are similarly expressed in
      epidermal mucous cells throughout embryogenesis and early larval stages. None of
      these newly identified FoxI genes are expressed in otic precursor cells and,
      therefore, are unlikely to share functional overlap with foxi1 in the development
      of the inner ear. In addition to these zebrafish FoxI paralogs, we have
      identified 16 new FoxI sequences in species ranging from Ciona intestinalis to
      Homo sapiens. We present an extensive phylogenetic analysis of the FoxI class
      that includes these new sequences together with those previously reported. This
      analysis supports the existence of three subfamilies within the FoxI class, each
      containing at least one zebrafish member.

PMID- 14579371
TI  - Expression of zebrafish Lc3 synthase gene in embryonic lens requires hedgehog
      signaling.
AB  - Glycosyltransferases are involved in synthesis of various glycolipids and
      glycoproteins that play important roles in many biological processes. We have
      identified a zebrafish gene encoding a member of beta1,3-N
      acetylglucosaminyltransferase family, the Lc3 synthase/bGn-T5. Whole-mount in
      situ hybridization reveals that the Lc3 synthase gene is expressed in two
      distinct phases during the zebrafish embryogenesis. The early phase extends from
      late blastulation to the completion of epiboly, during which the expression
      occurs in the superficial layer of the embryos. The second phase of expression
      starts during mid-segmentation and persists until day 3, during which the
      expression occurs prominently in the developing lens. The expression of the Lc3
      synthase gene in the lens is inhibited in you-too (yot) mutant embryos that are
      defective in Hedgehog signaling. The expression in the lens also decreases in
      cyclops (cyc) and one-eyed-pinhead (oep) mutant embryos and lefty1-injected
      embryos, which are deficient in Nodal signaling and lack Hedgehog activity in the
      ventral brain. These results suggest that Hedgehog signaling is required for the
      Lc3 synthase expression in embryonic lens.

PMID- 14579372
TI  - Integrity of the midbrain region is required to maintain the diencephalic
      mesencephalic boundary in zebrafish no isthmus/pax2.1 mutants.
AB  - Initial anterior-posterior patterning of the neural tube into forebrain,
      midbrain, and hindbrain primordia occurs already during gastrulation, in response
      to signals patterning the gastrula embryo. After the initial establishment,
      further development within each brain part is thought to proceed largely
      independently of the others. However, mechanisms should exist that ensure proper
      delineation of brain subdivisions also at later stages; such mechanisms are,
      however, poorly understood. In zebrafish no isthmus mutant embryos, inactivation
      of the pax2.1 gene leads to a failure of the midbrain and isthmus primordium to
      develop normally from the gastrula stage onward (Lun and Brand [1998] Development
      125:3049-3062). Here, we report that, after the initially correct establishment
      during gastrulation stages, the neighbouring forebrain primordium and, partially,
      the hindbrain primordium expand into the misspecified midbrain territory in no
      isthmus mutant embryos. The expansion is particularly evident for the posterior
      part of the diencephalon and less so for the first rhombomeric segment, the
      territories immediately abutting the midbrain/isthmus primordium. The nucleus of
      the posterior commissure is expanded in size, and marker genes of the forebrain
      and rhombomere 1 expand progressively into the misspecified midbrain primordium,
      eventually resulting in respecification of the midbrain primordium. We therefore
      suggest that the genetic program controlled by Pax2.1 is not only involved in
      initiating but also in maintaining the identity of midbrain and isthmus cells to
      prevent them from assuming a forebrain or hindbrain fate.

PMID- 14579373
TI  - Runx3 is required for hematopoietic development in zebrafish.
AB  - We cloned zebrafish runx3/aml2/cbfa3 and examined its expression and function
      during embryogenesis. In the developing embryo, runx3 is dynamically expressed in
      hematopoietic, neuronal, and cartilaginous tissues. Hematopoietic expression of
      runx3 commences late in embryogenesis in the ventral tail intermediate cell mass
      and later colocalizes with spi1 and lyz in circulating blood cells. In the cloche
      mutant, hematopoietic expression was absent, suggesting that Runx3 functions
      downstream of cloche in a hematopoietic pathway. Neuronal tissues expressing
      runx3 include the trigeminal ganglia and Rohon-Beard neurons. Runx3 appears to
      contribute to normal development of primitive and definitive hematopoietic cells.
      When Runx3 function was compromised using morpholino oligonucleotides, a
      reduction in the number of mature blood cells was observed. Furthermore, Runx3
      depletion decreased runx1 expression in the ventral wall of the dorsal aorta and
      reduced the number of spi1- and lyz-containing blood cells. Conversely,
      ubiquitous overexpression of runx3 led to an increase in primitive blood cell
      numbers, together with an increase in runx1-expressing cells in the ventral wall
      of the dorsal aorta. We propose a role for Runx3 in the regulation of blood cell
      numbers.

PMID- 14579374
TI  - Developmental morphology of the axial skeleton of the zebrafish, Danio rerio
      (Ostariophysi: Cyprinidae).
AB  - Before our rapidly increasing knowledge of gene interactions can be connected
      with the morphologic defects in mutant zebrafish, the normal course of skeletal
      development must be understood. Here, we describe the developmental morphology of
      the axial skeleton of zebrafish and review it in relation to the morphology of
      related species. The relative sequence of ossification in the skeleton is
      described. Two separate centers of development were found in the axial skeleton
      (Weberian apparatus and caudal fin) in contrast to tetrapods, which have a single
      anterior center. Slight variation was found in the overall relative timing of
      development. The extensive ichthyological literature on teleost anatomy and
      recent genetic data form the basis for our review and interpretation of
      homologies of various elements of the axial skeleton. Because homology forms the
      basis for all evolutionary comparisons, these data are critical for integration
      in evo-devo studies.

PMID- 14579375
TI  - Two divergent slit1 genes in zebrafish.
AB  - Members of the Slit family regulate axon guidance and cell migration. To date,
      three vertebrate slit1 genes have been identified in mammals and orthologs of
      two, slit2 and slit3, have been identified in zebrafish. Here, we describe the
      cloning of full-length cDNAs for two zebrafish slit orthologs, slit1a and slit1b.
      Both predicted proteins contain the conserved motifs that characterize other
      vertebrate Slits. slit1a and slit1b are both expressed in the midline, hypochord,
      telencephalon, and hindbrain. Apart from these shared expression domains,
      however, their expression patterns largely differ. Whereas slit1a is expressed
      broadly in the central nervous system (CNS) and in the somites, pectoral fin
      buds, tail bud, and caudal fin folds, slit1b is expressed in the olfactory system
      throughout embryonic and larval development, and in the retina during larval
      stages. Their expression patterns, particularly that of slit1a, suggest that Slit
      proteins may have roles in tissue morphogenesis in addition to their established
      roles in axon guidance and cell migration.

PMID- 14579376
TI  - Postembryonic development of the cranial lateral line canals and neuromasts in
      zebrafish.
AB  - The development of the cranial lateral line canals and neuromast organs are
      described in postembryonic zebrafish (0-80 days postfertilization). Cranial canal
      development commences several weeks after hatch, is initiated in the vicinity of
      individual neuromasts, and occurs in four discrete stages that are described
      histologically. Neuromasts remain in open canal grooves for several weeks during
      which they dramatically change shape and increase in size by adding hair cells at
      a rate one-tenth that in the zebrafish inner ear. Scanning electron microscopy
      demonstrates that neuromasts elongate perpendicular to the canal axis and the
      axis of hair cell polarization and that they lack a prominent nonsensory cell
      population surrounding the hair cells-features that make zebrafish neuromasts
      unusual among fishes. These results demand a reassessment of neuromast and
      lateral line canal diversity among fishes and highlight the utility of the
      lateral line system of postembryonic zebrafish for experimental and genetic
      studies of the development and growth of hair cell epithelia.

PMID- 14579377
TI  - Differential expression of Na,K-ATPase alpha and beta subunit genes in the
      developing zebrafish inner ear.
AB  - We have used whole-mount in situ hybridization to analyze Na,K-ATPase alpha and
      beta subunit gene expression in the developing zebrafish ear. Four alpha1-like
      (alpha1a.1, alpha1a.2, alpha1a.4, and alpha1a.5) and two beta (beta1a and beta2b)
      subunit genes are expressed in ear beginning at mid-somitogenesis. Each gene
      exhibits a distinct spatial and temporal expression pattern. The alpha1a.1 gene
      was ubiquitously expressed in the otic epithelium from mid-somitogenesis to 24 hr
      postfertilization (hpf). Expression of this gene was gradually reduced and by 48
      hpf, alpha1a.1 transcripts were no longer detectable in the ear. The alpha1a.2
      and alpha1a.5 genes were expressed in regions that correspond to the anterior
      macula, lateral crista, and semicircular canal projections up to 48 hpf. At later
      stages, expression of these genes was limited to cells in the dorsolateral septum
      and semicircular canal projections. alpha1a.4 and beta1a transcripts were
      ubiquitously expressed during ear development and were present in most otic
      tissues at 5 days postfertilization (dpf). Expression of the beta2b gene, on the
      other hand, was restricted to subsets of cells that form sensory epithelia. These
      results strongly suggest different functional roles for individual Na,K-ATPase
      genes in zebrafish ear development. Na,K-ATPase genes are likely to represent
      useful markers for the analysis of zebrafish otogenesis.

PMID- 14579378
TI  - Transgene driving GFP expression from the promoter of the zona pellucida gene zpc
      is expressed in oocytes and provides an early marker for gonad differentiation in
      zebrafish.
AB  - Although mechanisms of sex differentiation have been studied intensely in
      mammals, insects, and worms, little is known about this process in lower
      vertebrates. To establish a marker for female gonad differentiation in zebrafish,
      we generated a transgenic line in which 412 bp from the promoter and 5' mRNA
      leader of the female-specific zebrafish zona pellucida gene zpc are fused to the
      coding region of green fluorescent protein (GFP). The zpc0.5:GFP transgene is
      expressed exclusively in oocytes, starting from the onset of female-specific
      differentiation, and closely resembles the expression pattern of the wild-type
      zpc. Strong GFP expression persists throughout oogenesis and is visible through
      the body wall of females. We have also characterized a putative upstream factor
      of zpc, FIGalpha, and show that distribution of FIGalpha RNA is compatible with
      its postulated role in the regulation of zpc. The zpc0.5:GFP transgenic line
      described here will be useful for studying oocyte development and the mechanisms
      that determine sex-specific gene expression in the zebrafish. It is also the
      first promoter characterized to date to drive stable and efficient expression
      specifically in the zebrafish female germline.

PMID- 14579379
TI  - Targeted gene knockdown in zebrafish using negatively charged peptide nucleic
      acid mimics.
AB  - Negatively charged homo-oligomers of alternating trans-4-hydroxy-L
      proline/phosphonate polyamides with DNA bases (HypNA-pPNA) display excellent
      hybridization properties toward DNA and RNA, while preserving the mismatch
      discrimination, nuclease resistance, and protease resistance of peptide nucleic
      acids (PNAs). Similar properties are associated with morpholino
      phosphorodiamidate (MO) DNA mimics, which have been used in the model vertebrate
      zebrafish (Danio rerio) for genome-wide, sequence-based, reverse genetic screens
      during embryonic development. We evaluated mixed sequence HypNA-pPNAs as an
      alternative to MOs, and found that even a single central DNA mismatch lowered the
      HypNA-pPNA melting temperature by 16 degrees C. We then observed that the melting
      temperatures of HypNA-pPNA 18-mers hybridized to RNA 25-mers were comparable to
      the melting temperatures of MO 25-mers, and that two HypNA-pPNA mismatches
      lowered the melting temperature with RNA by 18 degrees C. In zebrafish embryos we
      observed that HypNA-pPNA 18-mers displayed comparable potency to MO 25-mers as
      knockdown agents against chordin, notail, and uroD, with greater mismatch
      stringency. Finally we observed that a specific HypNA-pPNA 18-mer elicited the
      dharma (bozozok)(-/-) phenotype in zebrafish embryos, which MO 25-mers do not.
      HypNA-pPNAs designed to inhibit translation of specific zebrafish RNA targets
      thus demonstrated stringent hybridization properties, relative to DNA and MO
      oligomers, and present a valuable alternative for reverse genetic studies,
      enabling the targeting of previously inaccessible genes.

PMID- 14579380
TI  - Histology-based screen for zebrafish mutants with abnormal cell differentiation.
AB  - The power of histology to define states of cell differentiation was used as the
      basis of a mutagenesis screen in zebrafish. In this screen, 7-day-old
      parthenogenetic half-tetrad larvae from potential carrier females were screened
      for mutations affecting cell differentiation in hematoxylin and eosin-stained
      tissue sections. Seven, noncomplementing, recessive mutations were found. Two
      mutations affect only the retina: segmented photoreceptors (spr) show a
      discontinuous photoreceptor cell layer; vestigial outer segments (vos) has fewer
      photoreceptor cells and degenerated outer segments within this cell layer. Three
      mutants have gut-specific defects: the epithelial cells of kirby (kby) are
      replaced by ballooned cells; the intestines of stuffy (sfy) and stuffed (sfd)
      contain increased luminal mucus. Two mutations affect multiple organs: disordered
      neural retina (dnr) has disrupted retinal layering and mild nuclear abnormalities
      in the gut and liver; and in huli hutu (hht), the retinal cell layers are
      disorganized and multiple organs have mild to severe nuclear abnormalities that
      are reminiscent of the atypia of human neoplasia. Each mutation appears to be
      homozygous lethal. This screen is proof of principle for the feasibility of
      histologic screens to yield novel mutations, including potential models of human
      disease. The throughput for this type of screen may be enhanced by automation.

PMID- 14579381
TI  - Direct binding of Lef1 to sites in the boz promoter may mediate pre-midblastula
      transition activation of boz expression.
AB  - The Nieuwkoop center provides signals essential for the establishment of the
      dorsal gastrula organizer in vertebrates. Activation of beta-catenin is one of
      the events in the Nieuwkoop center that lead to activation of dorsal-specific
      genes during blastula and early gastrula stages. Zebrafish bozozok (boz) mutant
      embryos have severe defects in axial mesoderm and anterior neuroectoderm. The boz
      gene is activated in the organizer in response to beta-catenin signaling, and Boz
      protein has been demonstrated to contribute to organizer formation by repression
      of ventralizing genes, including bmp2b, vega1, and vega2. Here, we investigate
      the timing and molecular mechanism by which boz expression is activated in the
      organizer. We demonstrate that boz is already expressed before midblastula
      transition (MBT). We further identify high-affinity binding sites for Tcf/Lef1
      within the boz promoter region. These sites, together with the finding that beta
      catenin induces boz expression, indicate that transcription of boz may be
      activated directly by beta-catenin/Lef1. We hypothesize that pre-MBT activation
      of boz may be important to build up a sufficiently strong antagonizing activity
      against zygotic ventralizing genes activated immediately post-MBT. Thus, the
      early onset of boz expression may be crucial for organizer establishment in the
      presence of ubiquitous maternal activators of ventralizing genes.

PMID- 14579382
TI  - gbx2 Homeobox gene is required for the maintenance of the isthmic region in the
      zebrafish embryonic brain.
AB  - We isolated cDNA clones for the zebrafish gbx2 gene, which is implicated in the
      establishment of the midbrain-hindbrain boundary (MHB) in other vertebrates.
      Spatially localized expression of gbx2 was observed at the MHB from 90% epiboly
      through to the hatching stage. Comparisons with the expression of otx2, wnt1, and
      krox20 showed that gbx2 is expressed in the anterior hindbrain. Ectopic
      expression of gbx2 by mRNA injection caused cyclopia or truncation of the fore-
      and midbrain and severely affected isthmic and cerebellar structures, while
      hindbrain formation was not significantly affected. At the molecular level, gbx2
      suppressed the expression of otx2 in the fore/midbrain, six3 in the anterior
      forebrain, and MHB-specific genes such as eng2 and wnt1. In contrast, gbx2 did
      not down-regulate the expression of the hindbrain marker genes. Therefore, gbx2
      specifically suppressed the formation of the entire fore/midbrain. Meanwhile,
      misexpression of otx2 suppressed the expression of gbx2 in the embryonic brain.
      Abrogation of gbx2 expression with an antisense morpholino oligonucleotide
      disrupted the midbrain/anterior hindbrain region, and these loss-of-function
      effects were rescued by activating the Gbx2 protein immediately after the end of
      gastrulation. Taken together, these results suggest that the zebrafish gbx2 gene
      is essential for the maintenance of MHB and/or the formation of the isthmic
      structure during somitogenesis, rather than for the MHB establishment during
      gastrulation. We also suggest that other factors, including gbx1, is required for
      the establishment of the MHB during gastrulation.

PMID- 14579384
TI  - Imaging brain development and organogenesis in zebrafish using immobilized
      embryonic explants.
AB  - Owing to its optical clarity and rapid rate of development, the zebrafish embryo
      is an ideal model system for studying the cellular mechanics of organogenesis.
      Unfortunately, extended time-lapse recordings of zebrafish embryos are often
      disrupted by the extension and straightening of the embryonic axis, as well as
      movement artifacts associated with developing musculature. In addition, the
      embryo's massive yolk cell often prevents optical access to tissues of interest.
      To circumvent these imaging problems, we have developed a procedure to deflate
      and mechanically remove the yolk cell. A "paralyzing" agent, AMP-PNP (a membrane
      impermeant nonhydrolyzable analog of ATP), is first injected into the embryo's
      contractile yolk cell. The yolk cell is then removed using sharpened tungsten
      needles. Deyolked embryos, or organ rudiments explanted from them, are then
      immobilized on a microscope coverslip using a thin plasma clot. This plasma clot
      immobilization allows novel mountings of the explants so that ventral, lateral,
      and even cross-sectional fields of views are possible using high numerical
      aperture objectives. We show that isolated head rudiments undergo normal
      morphogenesis and gene expression for at least 1 day after being explanted into
      organotypic culture. These procedures can be used to study the cellular mechanics
      of organogenesis in "deyolked" embryos, as well as in tissues explanted from
      green fluorescent protein transgenic animals.

PMID- 14579383
TI  - Neurogenic phenotype of mind bomb mutants leads to severe patterning defects in
      the zebrafish hindbrain.
AB  - Failure of Notch signaling in zebrafish mind bomb (mib) mutants results in a
      neurogenic phenotype where an overproduction of early differentiating neurons is
      accompanied by the loss of later-differentiating cell types. We have
      characterized in detail the hindbrain phenotype of mib mutants. Hindbrain
      branchiomotor neurons (BMNs) are reduced in number but not missing in mib
      mutants. In addition, BMN clusters are frequently fused across the midline in
      mutants. Mosaic analysis indicates that the BMN patterning and fusion defects in
      the mib hindbrain arise non-cell autonomously. Ventral midline signaling is
      defective in the mutant hindbrain, in part due to the differentiation of some
      midline cells into neural cells. Interestingly, while early hindbrain patterning
      appears normal in mib mutants, subsequent rhombomere-specific gene expression is
      completely lost. The defects in ventral midline signaling and rhombomere
      patterning are accompanied by an apparent loss of neuroepithelial cells in the
      mutant hindbrain. These observations suggest that, by regulating the
      differentiation of neuroepithelial cells into neurons, Notch signaling preserves
      a population of non-neuronal cells that are essential for maintaining patterning
      mechanisms in the developing neural tube.

PMID- 14579385
TI  - A MAGE/NDN-like gene in zebrafish.
AB  - The human necdin/MAGE gene family has over 50 members, but most of the proteins
      encoded by these genes are of unknown function. We have now identified a single
      locus in Danio rerio that encodes a putative protein with significant coding
      sequence similarity to the mammalian NDN/MAGE genes. Analysis of the complete
      Fugu ribripes genome sequence also suggests that there is only a single MAGE-like
      gene in teleost fish. mage is expressed in the larval and adult brain,
      specifically the retina, the medial region of the telencephalon, periventricular
      gray zone of the optic tectum, and most highly in the cerebellar corpus. The
      discovery of a zebrafish NDN/MAGE gene expressed the developing brain facilitates
      studies of the MAGE homology domain in vertebrate development.

PMID- 14579386
TI  - Genome duplication, subfunction partitioning, and lineage divergence: Sox9 in
      stickleback and zebrafish.
AB  - Teleosts are the most species-rich group of vertebrates, and a genome duplication
      (tetraploidization) event in ray-fin fish appears to have preceded this
      remarkable explosion of biodiversity. What is the relationship of the ray-fin
      genome duplication to the teleost radiation? Genome duplication may have
      facilitated lineage divergence by partitioning different ancestral gene
      subfunctions among co-orthologs of tetrapod genes in different teleost lineages.
      To test this hypothesis, we investigated gene expression patterns for Sox9 gene
      duplicates in stickleback and zebrafish, teleosts whose lineages diverged early
      in Euteleost evolution. Most expression domains appear to have been partitioned
      between Sox9a and Sox9b before the divergence of stickleback and zebrafish
      lineages, but some ancestral expression domains were distributed differentially
      in each lineage. We conclude that some gene subfunctions, as represented by
      lineage-specific expression domains, may have assorted differently in separate
      lineages and that these may have contributed to lineage diversification during
      teleost evolution.

PMID- 14579387
TI  - Genetic and genomic tools for zebrafish research: the NIH zebrafish initiative.
AB  - The National Institutes of Health (NIH) has been a leading advocate of the
      zebrafish as a model organism for the study of vertebrate development,
      physiology, and disease. Genomic tools, developed with the support of NIH
      funding, have made zebrafish even more attractive as a genetic system and have
      stimulated research using this model. The NIH continues to provide support for
      new and existing community resources, such as the Zebrafish International
      Resource Center and the Zebrafish Information Network, research tool development
      and mutant screens, and a wide array of investigator-initiated studies that are
      using zebrafish to elucidate many aspects of vertebrate biology.

PMID- 14579388
TI  - Current progress in neural crest cell motility and migration and future prospects
      for the zebrafish model system.
AB  - The neural crest is a unique population of cells that contributes to the
      formation of diverse cell types, including craniofacial cartilage, peripheral
      neurons, the cardiac outflow tract, and pigment cells. Neural crest cells (NCCs)
      are specified within the neuroepithelium, undergo an epithelial-to-mesenchymal
      transition, and migrate to target destinations throughout the embryo. Here, we
      review current understanding of two steps in NCC development, both of which
      involve NCC motility. The first is NCC delamination from the neuroepithelium and
      the changes in cell adhesion and the cytoskeleton necessary for the initiation of
      migration. The second is NCC migration and the signals that guide NCCs along
      specific migratory pathways. We illustrate the strength of the zebrafish, Danio
      rerio, as a model organism to study NCC motility. The zebrafish is particularly
      well suited for the study of neural crest motility because of the ability to
      combine genetic manipulation with live imaging of migrating NCCs.

PMID- 14579389
TI  - Zebrafish pronephros: a model for understanding cystic kidney disease.
AB  - The embryonic kidney of the zebrafish is the pronephros. The ease of genetic
      analysis and experimentation in zebrafish, coupled with the simplicity of the
      pronephros, make the zebrafish an ideal model system for studying kidney
      development and function. Several mutations have been isolated in zebrafish
      genetic screens that result in cyst formation in the pronephros. Cloning and
      characterization of these mutations will provide insight into kidney development
      but may also provide understanding of the molecular basis of cystic kidney
      diseases. In this review, we focus on the zebrafish as a model for understanding
      cystic kidney disease and the links between cystic kidney disease and left-right
      patterning.

PMID- 14579390
TI  - Insertional mutagenesis in zebrafish.
AB  - Insertional mutagenesis is a method for identifying genes essential for a given
      biological process by using the integration of DNA as the mutagen, thereby
      facilitating the cloning of the mutated gene. The use of retrovirus-mediated
      insertional mutagenesis in zebrafish has led to the mutation and rapid
      identification of hundreds of genes required for embryonic development and cell
      viability and growth, revealing the diversity of gene products required for the
      development of this vertebrate. Here, I will review the methodology of this
      approach and the results to date, as well as other potential ways to use
      insertional mutagenesis for genetic screens.

PMID- 14579391
TI  - Maternal factors in zebrafish development.
AB  - All processes that occur before the activation of the zygotic genome at the
      midblastula transition are driven by maternal products, which are produced during
      oogenesis and stored in the mature oocyte. Upon egg activation and fertilization,
      these maternal factors initiate developmental cascades that carry out the
      embryonic developmental program. Even after the initiation of zygotic gene
      expression, perduring maternal products continue performing essential functions,
      either together with other maternal factors or through interactions with newly
      expressed zygotic products. Advances in zebrafish research have placed this
      organism in a unique position to contribute to a detailed understanding of the
      role of maternal factors in early vertebrate development. This review summarizes
      our knowledge on the processes involved in the production and redistribution of
      maternal factors during zebrafish oogenesis and early development, as well as our
      understanding of the function of these factors in axis formation, germ layer and
      germ cell specification, and other early embryonic processes.

PMID- 14579392
TI  - Functional genomic dissection of multimeric protein families in zebrafish.
AB  - The study of multimeric protein function in the postgenomicera has become
      complicated by the discovery of multiple isoforms for each subunit of those
      proteins. A correspondingly large number of potential isoform combinations offer
      the multicellular organism a constellation of protein assemblies from which to
      generate a variety of functions across different cells, tissues, and organs. At
      the same time, the multiplicity of potential subunit isoform combinations
      presents a significant challenge when attempting to dissect the functions of
      particular isoform combinations. Biochemical and cell culture methods have
      brought us to a significant state of understanding of multimeric proteins but are
      unable to answer questions of function within the context of the many tissues and
      developmental stages of the multicellular organism. Answering those questions can
      be greatly facilitated in model systems in which expression can be determined
      over time, in the context of the whole organism, and in which hypomorphic
      function of each subunit can be studied individually and in combination.
      Fortunately, the potential for high-throughput in situ hybridization studies and
      antisense-based reverse genetic knockdowns in zebrafish offers exciting
      opportunities to meet this challenge. Some of these opportunities, along with
      cautions of interpretation and gaps in the existing technologies, are discussed
      in the context of ongoing investigations of the dimeric Na,K-ATPases and
      heterotrimeric G proteins.

PMID- 14579393
TI  - Modeling human hematopoietic and cardiovascular diseases in zebrafish.
AB  - Zebrafish have emerged as a useful vertebrate model system in which unbiased
      large-scale screens have revealed hundreds of mutations affecting vertebrate
      development. Many zebrafish mutants closely resemble known human disorders, thus
      providing intriguing prospects for uncovering the genetic basis of human diseases
      and for the development of pharmacologic agents that inhibit or correct the
      progression of developmental disorders. The rapid pace of advances in genomic
      sequencing and map construction, in addition to morpholino targeting and
      transgenic techniques, have facilitated the identification and analysis of genes
      associated with zebrafish mutants, thus promoting the development of zebrafish as
      a model for human disorders. This review aims to illustrate how the zebrafish has
      been used to identify unknown genes, to assign function to known genes, and to
      delineate genetic pathways, all contributing valuable leads toward understanding
      human pathophysiology.

PMID- 14579394
TI  - High field human imaging.
AB  - This review article examines the state of knowledge regarding human imaging using
      MRI at high main magnetic field strengths. The article starts with a summary of
      the technical issues associated with magnetic field strengths in the range of 3-8
      T, including magnet characteristics and the properties of radiofrequency magnetic
      fields, with special reference to sensitivity, power deposition, and homogeneity.
      The published data on tissue-water relaxation times in the brain is tabulated and
      the implications for contrast and pulse sequence implementation is elucidated.
      The behavior of the major fast imaging sequences, fast low angle shot (FLASH),
      rapid acquisition with relaxation enhancement (RARE), and echo planar imaging
      (EPI), is examined in this context. A number of anatomical images from 3 T
      systems are presented as examples. Particular attention is given to various forms
      of vascular imaging, namely, time of flight angiography, venography, and arterial
      spin labeling. The most complex changes in contrast with main magnetic field
      strength are in activation studies utilizing the blood oxygen level dependent
      mechanism, which are examined in detail. Improvements in spatial specificity are
      emphasized, particularly in conjunction with spin-echo imaging. The article
      concludes with a discussion of the current status and the potential impact of
      technical developments such as parallel imaging.

PMID- 14579395
TI  - Magnetic resonance image-guided proteomics of human glioblastoma multiforme.
AB  - PURPOSE: To investigate the correlation between gadolinium contrast-enhancement
      patterns on T1-weighted magnetic resonance (MR) images and spatial changes in
      protein expression profiles in human glioblastoma multiforme (GBM) and the use of
      imaging as a noninvasive technique to evaluate the heterogeneity of solid tumors
      prior to microarray analysis. MATERIALS AND METHODS: Four patients with MR images
      and confirmed diagnosis of GBM were enrolled in the study. Intraoperative
      stereotaxy was used in conjunction with MR images to identify contrast-enhanced
      (CE) and nonenhanced (NE) regions of the tumor during surgical resection. Total
      protein was extracted from resected tumor samples using standard techniques and
      subjected to proteomic analysis using surface enhanced laser
      desorption/ionization time of flight mass spectrometry (SELDI-TOF-MS). RESULTS:
      We found that protein profiles from CE and NE regions within a given tumor have
      qualitative and semiquantitative proteomic pattern differences, suggesting an
      altered gene expression profile that correlates with detectable tissue imaging
      parameters. We also found that CE regions within the same tumor exhibited
      distinct differences in protein expression profiles, despite similar histological
      features. In addition, there were marked similarities in the proteomic patterns
      among the NE regions across all patients, while the CE regions were distinct,
      suggesting that the CE regions have complex protein profiles unique to
      individuals. CONCLUSION: The results demonstrate that major differences in
      protein expression patterns within a tumor can be correlated to radiographic
      findings. Image-guided proteomics holds promise for characterizing tissue prior
      to microarray analysis designed to identify specific diagnostic markers and
      therapeutic targets within solid tumors.

PMID- 14579396
TI  - Magnetization transfer imaging and magnetic resonance spectroscopy of normal
      appearing white matter in late-life major depression.
AB  - PURPOSE: To examine the relationships between the damaged macromolecular pool
      seen on magnetization transfer (MT) imaging and cerebral metabolic changes
      recorded by magnetic resonance spectroscopy (MRS), in frontal white and gray
      matter regions of late-life MDD patients. MATERIALS AND METHODS: MT imaging and
      MRS were performed on eight patients with late-life MDD and eight age-matched
      healthy controls. MT ratios were calculated using the on-resonance and off
      resonance images. Correlations were computed between MT ratios and the ratios of
      several metabolites, including choline (Cho), myo-inositol (mI), N
      acetylaspartate (NAA), and N-acetylaspartylglutamate (NAAG), to creatine (Cr).
      RESULTS: Statistically significant correlations were found in white matter
      between the MT ratios and mI/Cr (r = -0.90, N = 7, P = 0.016), and between the MT
      ratios and (NAA + NAAG)/Cr (r = -0.89, N = 8, P = 0.007). No significant
      correlations were found in gray matter or between the MT ratios and NAA/Cr or
      Cho/Cr in white matter. CONCLUSION: Changes in the white matter macromolecular
      protein pool, observed as reduced MT ratios, may be related to changes in the mI
      and the total NAA pools. These findings may have implications for the
      pathophysiology of late-life major depression.

PMID- 14579397
TI  - Magnetic resonance imaging of myocardial contrast enhancement with MS-325 and its
      relation to myocardial blood flow and the perfusion reserve.
AB  - PURPOSE: To determine with an intravascular contrast agent the relation between
      the rate of myocardial signal enhancement during the first pass (upslope) and
      myocardial blood flow (MBF), and to derive and validate a corrected perfusion
      reserve (PR) index from the upslope parameter. MATERIALS AND METHODS:
      Measurements of the upslope parameter for myocardial contrast enhancement with an
      intravascular contrast agent (MS-325) were performed in a porcine model with
      ameroid coronary constrictor. MBF was estimated with MRI and was validated
      against separate invasive measurements with labeled microspheres. PR indices were
      calculated from the upslope of the tissue curves. A new PR index was corrected by
      the time delay between appearance of the tracer and the upslope maximum. RESULTS:
      MBFs determined by MRI vs. MBFs measured with microspheres were in agreement
      within the 95% confidence intervals (CIs) for the identity relation. The new PR
      index slightly overestimated the MBF reserve by an average +1.4% (95% CI = -44%
      to +46%). The uncorrected PR index underestimated the MBF reserve by -33% (95% CI
      = -92% to +25%). CONCLUSION: A perfusion index derived from the maximum upslope
      of myocardial contrast enhancement produces accurate estimates of the PR if
      corrected by the time-to-maximum upslope.

PMID- 14579398
TI  - Quantitative assessment of myocardial perfusion with a spin-labeling technique:
      preliminary results in patients with coronary artery disease.
AB  - PURPOSE: To determine perfusion and coronary reserve in human myocardium without
      contrast agent using a spin labeling technique. MATERIALS AND METHODS: Assessment
      of myocardial perfusion is based on T1 measurements after global and slice
      selective spin preparation. This magnetic resonance imaging (MRI) technique was
      applied to 12 healthy volunteers and 16 patients with suspected coronary artery
      disease under resting conditions and adenosine-induced vasodilatation. RESULTS:
      In volunteers, quantitative perfusion was calculated as 2.4 +/- 1.2 mL/g/minute
      (rest) and 3.9 +/- 1.3 mL/g/minute (adenosine), respectively. Perfusion reserve
      was 2.1 +/- 0.6. In patients, when comparing perfusion reserve in the anterior
      and posterior myocardium, reduced values according to a stenotic supplying vessel
      could be seen in seven of 11 patients who underwent stress testing. In these
      patients, the relative difference of coronary reserve was 44% +/- 18%. Two
      patients without stenosis of coronary arteries showed no differences in coronary
      reserve (with a relative change of 2 +/- 2%). CONCLUSION: In patients with single
      vessel coronary artery disease, differences in coronary reserve were clearly
      detectable when comparing anterior and posterior myocardium. The spin labeling
      method is noninvasive and easily repeatable, and it could therefore become an
      important tool to study changes in myocardial perfusion.

PMID- 14579399
TI  - Right posterior hepatic notch sign: a simple diagnostic MR finding of cirrhosis.
AB  - PURPOSE: To determine the frequency of occurrence of the right posterior hepatic
      notch sign at MR imaging in patients with cirrhosis, and to assess its diagnostic
      capability of this sign as a simple diagnostic MR finding of cirrhosis. MATERIALS
      AND METHODS: This study population included 330 patients with pathologically
      proved cirrhosis (N = 202) or without clinical evidence of chronic liver diseases
      (N = 128, control group). MR images were qualitatively evaluated for the presence
      of the right posterior hepatic notch sign. This sign was considered present if
      there was a sharp notch in the right posterior surface of the liver. The presence
      of the expanded gallbladder fossa sign was also evaluated during the same reading
      session. RESULTS: The right posterior hepatic notch sign was observed in 145 of
      the 202 patients in the cirrhosis group, while this sign was seen in only two of
      the 128 patients in the control group (P < 0.0001). The sensitivity, specificity,
      and accuracy of this sign for the MR diagnosis of cirrhosis were 72%, 98%, and
      82%, respectively. When the presence of either the expanded gallbladder fossa
      sign or the right posterior hepatic notch sign was considered for the MR
      diagnosis of cirrhosis, the sensitivity and accuracy increased to 86% and 89%,
      respectively. CONCLUSION: The right posterior hepatic notch sign can be used as a
      simple and highly specific sign of cirrhosis, if present. The diagnostic
      performance can be improved when the presence of either the expanded gallbladder
      fossa sign or the right posterior hepatic notch sign was considered.

PMID- 14579400
TI  - Centrally fat-saturated three-dimensional magnetic resonance angiography of the
      abdomen using selective central fat-saturation of k-space.
AB  - PURPOSE: To assess the usefulness of centrally fat-saturated three-dimensional
      magnetic resonance (MR) angiography of the abdomen using an elliptical centric
      view order and selective placement of fat-saturation pulses in the central 30%
      portion of the k-space in terms of fat signal reduction, image contrast of post
      contrast images, and breath-holding time. METHODS: Fat signal in abdomen and
      breath-holding time were compared between centrally fat-saturated three
      dimensional sequence and partially fat-saturated three-dimensional sequence or
      conventional fat-saturated three-dimensional sequence. Abdominal contrast
      enhanced centrally fat-saturated three-dimensional MR angiography was obtained at
      arterial and equilibrium phases, and image quality was quantitatively and
      visually evaluated. RESULTS: Centrally fat-saturated three-dimensional sequence
      suppressed fat signal, as did the conventional fat-saturated three-dimensional
      sequence, and the breath-hold was prolonged only by 1.5 seconds compared to the
      partially fat-saturated three-dimensional sequence. Contrast-enhanced centrally
      fat-saturated three-dimensional MR angiography provided abdominal MR
      arteriography with large signal difference between vessels and fat, while venous
      signal was insufficient at equilibrium phase. CONCLUSION: Abdominal contrast
      enhanced centrally fat-saturated three-dimensional MR angiography using an
      elliptical centric view order and selective central fat-saturation of k-space
      reduced fat signal comparable to conventional fat-saturated three-dimensional
      sequence, and provided contrast-enhanced MR arteriography with high vascular
      contrast and minimum prolongation of breath-hold.

PMID- 14579401
TI  - Determining and optimizing the precision of quantitative measurements of
      perfusion from dynamic contrast enhanced MRI.
AB  - PURPOSE: To examine the sensitivity of quantitative dynamic contrast enhanced MRI
      (DCE-MRI) perfusion maps to errors in the various source images and to determine
      optimal imaging parameters for reducing this sensitivity. MATERIALS AND METHODS:
      A detailed analysis of the precision of a DCE-MRI protocol was performed using
      the "propagation of errors" technique to investigate the effect of errors in the
      source images on errors in K(trans). Optimal parameter values and interactions
      between parameters were examined. The propagation of errors analysis was
      validated by Monte-Carlo simulations. RESULTS: The precision of K(trans) was
      found to be most sensitive to artifacts in the tissue portion of the baseline
      images and least sensitive to noise in the arterial portion of the dynamic
      images. The tip-angle strongly affected the precision, with the optimum being a
      function of tissue T1(0). CONCLUSION: Protocol optimization requires matching the
      tip-angle to the anticipated T1(0) of the tissue of interest; however such
      optimization yields a relatively small improvement. Future developmental efforts
      would be most productively focused on minimizing the artifact level.

PMID- 14579402
TI  - Prediction of subtle thermal histopathological change using a novel analysis of
      Gd-DTPA kinetics.
AB  - PURPOSE: To investigate Gd-DTPA kinetics as predictors of histopathological
      changes following focused ultrasound (FUS) thermal ablation for improved planning
      and assessment. MATERIALS AND METHODS: Twenty-nine FUS lesions were created in
      the thigh muscle of eight rabbits under MR-guidance at 1.5 Tesla. Three rabbits
      were killed at four hours; and 11 lesions were analyzed with histopathology.
      Temperature-sensitive MRI using proton-resonant frequency-shift was used for time
      dependent temperature measurements. Analysis of the uptake kinetics of Gd-DTPA
      was performed after Gd-DTPA injection, within 20 minutes after heating and again
      at two hours after heating. The resulting kinetic maps, permeability (K(trans))
      and leakage space (v(e)), were correlated to peak temperatures, T(2)-weighted MR,
      and histopathology. RESULTS: Images of K(trans) and v(e) reveal regions of
      histopathological change not visible on conventional post-therapy MR. At early
      times after heating, v(e) predicts the area of injury more accurately than T(2)
      (7 +/- 2% vs. 25 +/- 6% underestimation). A circular region of extensive
      structural/vascular disruption is indicated only on K(trans) maps. The sharp
      decrease in K(trans) at the boundary of this region occurs at 47.5 +/- 0.5
      degrees C, and may be a better estimate of cell death than the conventional
      method of temperature threshold (55 degrees C for coagulation) used in therapy
      planning. CONCLUSION: Our results suggest Gd-DTPA kinetics can predict different
      histopathological changes following FUS ablation and may be valuable for early
      prediction.

PMID- 14579403
TI  - Event-related analysis for event types of fixed order and restricted spacing by
      temporal quantification of trial-averaged fMRI time courses.
AB  - PURPOSE: To develop a method for event-related fMRI that allows rapidly presented
      event sequences to be analyzed, without requiring transitions of different event
      types to be counterbalanced. MATERIALS AND METHODS: A cued task switching
      procedure was investigated with an experimental trial comprising a visual task
      cue that indicated how to process a subsequent visual target stimulus. Cue and
      target were either presented quasi-simultaneously, separated by a 100 msec cue
      target-interval (CTI100), or the target presentation was delayed by 2000 msec
      (CTI2000). To characterize the trial-related BOLD-response in terms of its
      temporal relation to the underlying event structure, the pattern of onset latency
      differences and peak latency differences for CTI2000 minus CTI100 was evaluated.
      Independent estimates of onset latencies and peak latencies were determined for
      preprocessed trial-averaged time courses by jackknife resampling. RESULTS:
      Validating results were obtained for two brain areas with known characteristics:
      the visual cortex (cue-locked plus target-locked activation) and the motor cortex
      (response-locked activation). Extending the analysis to prefrontal areas with a
      priori unknown characteristics differentiated between several meaningful temporal
      activation patterns. CONCLUSION: The method yielded a fine-grained temporal
      description of trial-related BOLD-responses that could be successfully used for
      the event-related analysis of an experimental design that was highly restricted
      with respect to event order and event spacing.

PMID- 14579404
TI  - Giant adrenal myelolipoma with minimal fat content in a patient with homozygous
      beta-thalassemia: appearance on MRI.
AB  - Giant adrenal myelolipoma is an uncommon entity. We present the atypical MR
      imaging findings of a giant adrenal myelolipoma in a patient with homozygous beta
      thalassemia with histopathology correlation. The tumor showed a drop in signal on
      the opposed-phase images, with no evidence of macroscopic fat contents, and
      demonstrated very high signal intensity on T2-weighted images. Giant adrenal
      myelolipoma should be considered in the differential diagnosis of tumors with the
      combination of the above MR imaging characteristics.

PMID- 14579405
TI  - Automatic in-plane rotation for doubly-oblique cardiac imaging.
AB  - PURPOSE: To develop and test a method for automatically calculating the in-plane
      rotation for doubly-oblique slice geometry in order to minimize wrap artifacts
      for a given FOV. MATERIALS AND METHODS: The equations for in-plane rotation were
      formulated for doubly-oblique imaging of a cylindrical body with elliptical cross
      section. Based on this formulation, automatic in-plane rotation was implemented
      and tested on a commercial scanner using nominal values for ellipticity of the
      body. RESULTS: Short axis, doubly oblique, cardiac imaging were acquired with and
      without in-plane rotation. The desired in-plane rotation proved to be relatively
      insensitive to the ellipticity of the body, permitting an automatic solution
      based on a nominal value. CONCLUSION: In-plane rotation is desirable for doubly
      oblique imaging (e.g., cardiac applications), particularly for reduced-FOV
      accelerated imaging such as SENSE. The proposed method, which provides an
      approximate solution for automatic, in-plane rotation for doubly-oblique imaging,
      was demonstrated.

PMID- 14579406
TI  - Interscanner reproducibility of cardiovascular magnetic resonance T2*
      measurements of tissue iron in thalassemia.
AB  - PURPOSE: To assess interscanner reproducibility of tissue iron measurements in
      patients with thalassemia using gradient echo T2* measurements on two different
      MRI scanners. MATERIALS AND METHODS: Twenty-five patients with thalassemia major
      had liver and myocardial T2* assessment using a Picker Edge 1.5T Scanner and a
      Siemens Sonata 1.5T scanner, with similar gradient echo sequences. In a subset of
      13 patients, two scans on the Siemens scanner were performed to assess interstudy
      reproducibility. RESULTS: There was a highly significant, linear correlation
      between T2* values obtained for both the heart (r = 0.95) and the liver (r =
      0.99) between scanners. The mean difference, coefficient of variability, and 95%
      confidence intervals between scanners were 0.8 msec, 9.4% and -5.0 to 6.7 msec
      for the heart; and 0.9 msec, 7.9% and -2.0 to 3.9 msec for the liver. The
      interstudy mean difference and coefficient of variability on the Siemens scanner
      was 0.3 msec and 4.8% (r = 0.99) for the heart, and 0.04 msec and 1.9% (r = 0.99)
      for the liver. CONCLUSION: The T2* technique for measuring tissue iron is
      reproducible between the two manufacturers' scanners. This suggests that the
      widespread implementation of the technique is possible for clinical assessment of
      myocardial iron loading in thalassemia.

PMID- 14579407
TI  - Real-time catheter tracking and adaptive imaging.
AB  - PURPOSE: To evaluate the performance of a real-time MR system for interventional
      procedures that adjusts specific image parameters in real time based on a
      catheter's speed of insertion. MATERIALS AND METHODS: The system was implemented
      using only the hardware provided with a standard short-bore 1.5 T scanner
      (Siemens Magnetom Sonata) (with the exception of small tracking markers affixed
      to the catheter). The system tracks the position of an MR microcoil-instrumented
      catheter and automatically updates the scan plane's position and orientation, as
      well as other features, including, but not limited to, field of view, resolution,
      tip angle, and TE. A real-time feedback loop continuously localizes the tracking
      markers, updates the scan plane position and orientation, calculates the
      catheter's speed, adjusts the value of specific image parameters, then collects
      new image data, reconstructs an image, and provides it for immediate display. The
      system was evaluated in phantom and in vivo porcine experiments. RESULTS: The
      system is able to accurately localize a moving catheter in the abdominal aorta,
      calculate the device speed, and respond by adjusting specified image parameters
      98% of the time, with precision of approximately 2 mm and 1.5 degrees.
      CONCLUSION: Simply slowing the speed of the catheter allows the clinician to
      adjust predetermined image parameters. This work also has the potential to build
      a degree of intelligence into the scanner, enabling it to react to changes in the
      clinical environment and automatically optimize specific image parameters.

PMID- 14579408
TI  - cDNA nucleotide sequence coding for stearoyl-CoA desaturase and its expression in
      the zebrafish (Danio rerio) embryo.
AB  - A cDNA sequence of stearoyl-CoA desaturase (SCD) was determined from zebrafish
      (Danio rerio) and compared to the corresponding genes in several teleosts.
      Zebrafish SCD cDNA has a size of 1,061 bp, encodes a polypeptide of 325 amino
      acids, and shares 88, 85, 84, and 83% similarities with tilapia (Oreochromis
      mossambicus), grass carp (Ctenopharyngodon idella), common carp (Cyprinus
      carpio), and milkfish (Chanos chanos), respectively. This 1,061 bp sequence
      specifies a protein that, in common with other fatty acid desaturases, contains
      three histidine boxes, believed to be involved in catalysis. These observations
      suggested that SCD genes are highly conserved. In addition, an oligonucleotide
      probe complementary to zebrafish SCD mRNA was hybridized to mRNA of approximately
      396 bases with Northern blot analysis. The Northern blot and RT-PCR analyses
      showed that the SCD mRNA was expressed predominantly in the liver, intestine,
      gill, and muscle, while a lower level was found in the brain. Furthermore, we
      utilized whole-mount in situ hybridization and real-time quantitative RT-PCR to
      identify expression of the zebrafish SCD gene at five different stages of
      development. This revealed that very high levels of transcripts were found in
      zebrafish at all stages during embryogenesis and early development.

PMID- 14579409
TI  - Gene expression and in vitro development of inter-species nuclear transfer
      embryos.
AB  - This study examined the chromatin morphology, in vitro development, and
      expression of selected genes in cloned embryos produced by transfer of mouse
      embryonic fibroblasts (MEF) into the bovine ooplasm. After 6 hr of activation,
      inter-species nuclear transfer (NT) embryos (MEF-NT) had one (70%) or two
      pronuclei (20%), respectively. After 72 hr of culture in vitro, 62.6% of the MEF
      NTs were arrested at the 8-cell stage, 31.2% reached the 2- to 4-cell stage, and
      only 6.2% had more than eight blastomeres, but none of these developed to the
      blastocyst stage. Whereas, 20% of NT embryos derived from bovine embryonic
      fibroblast fused with bovine ooplasm (BEF-NT) reached the blastocyst stage. Donor
      MEF nuclei expressing an Enhanced Green Fluorescent Protein (EGFP) transgene
      resulted in 1- to 8-cell stage MEF-NT that expressed EGFP. The expression of
      selected genes was examined in 8-cell MEF-NTs, 8-cell mouse embryos, enucleated
      bovine oocytes, and MEFs using RT-PCR. The mRNA for heat shock protein 70.1 (Hsp
      70.1) gene was detected in MEF-NTs and MEF, but not in mouse embryos. The hydroxy
      phosphoribosyl transferase (HPRT) mRNA was found in normal mouse embryos and MEF
      but not in MEF-NTs. Expression of Oct-4 and embryonic alkaline phospatase (eAP)
      genes was only detected in normal mouse embryos and not in the inter-species NT
      embryos. Abnormal gene expression profiles were associated with an arrest in the
      development at the 8-cell stage, but MEF-NT embryos appeared to have progressed
      through gross chromatin remodeling, typical of intra-species NT embryos.
      Therefore, molecular reprogramming rather than chromatin remodeling may be a
      better indicator of nuclear reprogramming in inter-species NT embryos.

PMID- 14579410
TI  - Cyclin A2 is phosphorylated during the G2/M transition in mouse two-cell embryos.
AB  - In the present study, we investigated the expression of cyclin A2 in mouse two
      cell embryos to elucidate the role of cyclin A2 at the G2/M transition. Two forms
      of cyclin A2 on SDS-PAGE (an upper and a lower band) were detected in two-cell
      embryos synchronized at the M phase by nocodazole. To investigate the nature of
      this shift, embryos synchronized at the M phase were treated with alkaline
      phosphatase (AP). The upper band of cyclin A2 was fainter in AP-treated embryos
      than in nontreated embryos. This result indicates that cyclin A2 in mouse two
      cell embryos is phosphorylated and the band on SDS-PAGE shifts up during the G2/M
      transition. In addition, we examined the sequential expression of cyclin A2 in
      two-cell blocked embryos after OA treatment. The upper band of cyclin A2 was
      first detected at 2 hr after the treatment, corresponding to the timing of Cdc2
      kinase activation. In two-cell embryos after removal from nocodazole treatment,
      the phosphorylated form of cyclin A2 protein decreased abruptly just before
      cytokinesis. These results suggest that the mechanism of cyclin A2 degradation in
      mouse two-cell embryos may be different from that in somatic cells.

PMID- 14579411
TI  - Novel purification method for mammalian seminal plasma phospholipid-binding
      proteins reveals the presence of a novel member of this family of protein in
      stallion seminal fluid.
AB  - A family of bull seminal plasma (BSP) phospholipid-binding proteins (BSP
      proteins), potentiate heparin- and HDL-induced capacitation. The homologous
      proteins have been purified from stallion and boar seminal plasma, and detected
      in low concentrations in other mammalian seminal plasma. In this study, we
      developed a new isolation method for mammalian seminal plasma choline
      phospholipid-binding proteins wherein they are present in low concentrations. The
      method is based on the interaction of this family of proteins with egg yolk low
      density lipoprotein fraction (LDF). In order to demonstrate the feasibility of
      the method, we incubated LDF with alcohol precipitates of bull, boar, and
      stallion seminal plasma. LDF were re-isolated by ultracentrifugation along with
      bound proteins. LDF with associated proteins were dialyzed, lyophilized, and
      delipidated. BSP homologous proteins were finally purified by p-aminophenyl
      phosphorylcholine (PPC)-agarose and/or gelatin-agarose chromatographies, and
      analyzed by SDS-PAGE. With this new protocol, phospholipid-binding proteins of
      bull, boar, and stallion seminal plasma were recovered almost 100%. A new 12 kDa
      stallion seminal plasma protein of the same family was also isolated and
      partially sequenced. The radio-immunoassay (RIA) data showed that 10 mg of LDF
      can bind all BSP proteins present in 120 mg of alcohol precipitated BSP proteins.
      These results confirm the efficiency of the method and that the LDF step could be
      used for the isolation of all BSP proteins homologs from different mammalian
      species.

PMID- 14579412
TI  - Characterization of cell- and region-specific abnormalities in the epididymis of
      cathepsin A deficient mice.
AB  - Cathepsin A (PPCA), a lysosomal carboxypeptidase that functions as a protective
      protein for alpha-neuraminidase and beta-galactosidase in a multi-enzyme complex,
      has been shown to be expressed in the epithelial cells of the epididymis. In the
      present study, the epididymis of PPCA-/- mice from 2 to 10 months of age was
      compared with those of their wild-type counterparts. Major accumulations of pale
      vacuoles, corresponding to lysosomes, were noted in principal and narrow/apical
      cells in PPCA-/- mice, and clear cells also appearing highly vacuolated, were
      grossly enlarged in size. This was especially evident in the caput and corpus
      regions, where quantitative analyses confirmed that the epithelium of the tubules
      in these regions was expanding in profile area. In addition, the base of the
      epithelium in these regions was often greatly vacuolated, corresponding to cells
      that presented no identifiable features and appeared to be degenerating. Halo
      cells dispersed at various levels in the epithelium also appeared to be abnormal,
      accumulating pale lysosomes. Furthermore, numerous macrophages were observed in
      the intertubular space of the entire duct, presenting a large size and plethora
      of pale lysosomes. Taken together, the present data indicate major lysosomal
      abnormalities in the epididymis of PPCA-/- mice in a cell type and region
      specific manner. In addition, it is suggested that the compromised halo cells,
      due to PPCA deficiency within their lysosomes, cannot function properly and as a
      result there is a recruitment of macrophages in the intertubular space.

PMID- 14579414
TI  - One step purification and biochemical characterization of a spermatozoa-binding
      protein from porcine oviductal epithelial cells.
AB  - In pigs the binding of sperm to oviductal epithelial cells to form a sperm
      reservoir involves carbohydrate interactions. In the present study, we purify a
      sperm binding glycoprotein (SBG) from cells from the isthmus of the oviduct using
      an affinity column. This protein conjugated with FITC is able to bind to the
      heads of pig sperm. SBG is shown to contain carbohydrates by PAS-silver staining
      and lectin binding assays. Enzymatic treatment and lectin affinity demonstrate
      that SBG exposes Galbeta1-3GalNAc disaccharide, which is bound to a serine or a
      threonin residue by an O-link. After enzymatic deglycosylation SBG shows an
      apparent molecular mass of 67.5 kDa, which changes to 85 kDa by reduction with 2
      mercaptoethanol. Both SBG and enzymatically deglycosylated SBG show by
      isoelectrofocusing two forms of pI 3.6 and pI 3.8. SBG may be involved on sperm
      oviduct interaction.

PMID- 14579413
TI  - Accumulation of zinc, copper, and metallothionein mRNA in lizard ovary proceeds
      without a concomitant increase in metallothionein content.
AB  - The possible role of metallothionein (MT) in metal homeostasis has been
      investigated in growing oocytes and eggs of the lizard Podarcis sicula.
      Chromatographic analysis does not reveal the presence of MT in both ovary and
      eggs, the only metal-binding proteins detected being represented by high
      molecular mass components. De novo synthesis of MT could be observed in the ovary
      of cadmium-treated lizards. A cDNA encoding MT was obtained from the liver of P.
      sicula by RT-PCR followed by a RACE strategy, using primers designed on consensus
      motifs of vertebrate MT. In spite of the lack of MT in the ovary of untreated
      animals, Northern blot analysis demonstrates that the maternal untranslated MT
      transcript is expressed constitutively in the ovary in all the periods of the
      ovarian cycle. MT mRNA content increases during the oocyte growth, reaching the
      highest level in ovulated eggs, concomitantly with the accumulation of zinc and
      copper. Our findings suggest that maternal MT mRNA accumulates in the egg and is
      translated sometime during development to cope with the future needs of the
      growing embryo. The appearance of MT after cadmium treatment suggests that the
      block that makes the oocytarian MT mRNA untranslatable is removed by the metal.

PMID- 14579415
TI  - Immunocytochemical localization of DJ-1 in human male reproductive tissue.
AB  - DJ-1 was identified as an activated ras-dependent oncogene product, and was also
      found to be an infertility-related protein (contraception-associated protein 1;
      CAP 1) that was reduced in rat spermatozoa treated with ornidazole, one of the
      endocrine disrupting substances that causes reversible infertility in rats. CAP 1
      is present in spermatozoa but is not detectable in the epididymal fluid of
      fertile rats and appears to be shed from sperm during treatment with ornidazole.
      To determine the functions of DJ-1 in the human reproductive system as a target
      protein of endocrine active substances, we identified the localization of DJ-1 in
      human testis, epididymis, ejaculated spermatozoa, and seminal plasma. DJ-1 was
      present in cells existing in the seminiferous tubules and Leydig cells. Some
      strong expressions were observed in Leydig cells and Sertoli cells, suggesting a
      relation with spermatogenesis via androgen receptor (AR). In ejaculated
      spermatozoa, DJ-1 existed on the surface of the posterior part of head and the
      anterior part of the midpiece. DJ-1 was also present on sperm flagella when the
      antibody penetrated the plasma membrane, suggesting that there are two putative
      roles in fertilization, one is binding to the egg, and the other is flagella
      movement. In contrast to previous findings, we detected DJ-1 in seminal plasma of
      fertile men. These results demonstrate that DJ-1 in human seminal plasma is not
      only from spermatozoa but also from the testis and epididymis. It is suggested
      that DJ-1 may play an important and as yet uncharacterized role in
      spermatogenesis and fertilization in humans.

PMID- 14579416
TI  - Changes in JNK1 activity in the frog (Rana esculenta) testis.
AB  - Several lines of evidences support a key role of mitogen-activated protein
      kinases (MAPK) in male fertility. It has been used as a non-mammalian vertebrate
      model, the frog Rana esculenta, to investigate the regulation of Jun amino
      terminal kinase 1 (JNK1) activity in the testis in two different periods of the
      annual reproductive cycle: winter stasis and breeding season. JNK1 protein was
      localized by immunohistochemistry in the cytoplasm and nucleus of spermatogonia
      (SPG) and spermatocytes (SPC) during all the year. Immunoprecipitation analysis
      of JNK1 clearly shows that this isoform presents a strong phosphorylation status
      (thr183/Tyr185) in the breeding period, in contrast with only very low activity
      during the winter stasis. Simultaneously, during the breeding period c-Jun
      protein is highly phosphorylated on Ser-63. These data suggest that the increase
      of JNK1 activity, with strong c-Jun phosphorylation (Ser-63) during the breeding
      period, could be the signal of increasing transcriptional activity in the frog
      testis.

PMID- 14579417
TI  - Feasibility of global gene expression analysis in testicular biopsies from
      infertile men.
AB  - Numerous studies have documented the use of microarray analysis to identify
      patterns of global gene expression that distinguish normal development from that
      of the diseased state. Yet, there are no reports that compare global gene
      expression in the fertile and infertile human testis. Here, we report an initial
      study of global gene expression in testicular biopsies from several men with
      different infertility phenotypes. We found that microarray analysis of small
      biopsy samples was suitable for profiling expression of genes known to function
      in germ cell development and also identified expression of novel genes. Since it
      is now common for infertile men with spermatogenic failure to use
      intracytoplasmic sperm injection (ICSI) to achieve biological paternity, we
      hypothesize that molecular screening of testicular biopsies with microarrays may
      be suitable: (1) to categorize the molecular phenoytpes of infertile testes in a
      manner similar to standard morphologic analysis and (2) to initiate larger
      studies of gene expression in the infertile testes that may identify genetic
      signatures from biopsies that allow prediction of outcomes.

PMID- 14579418
TI  - Superoxide dismutase content and fatty acid composition in subsets of human
      spermatozoa from normozoospermic, asthenozoospermic, and polyzoospermic semen
      samples.
AB  - Human ejaculated sperm comprised discrete subsets of spermatozoa, with different
      degrees of maturation. These subpopulations can be isolated through density
      gradient centrifugation. Sperm from the lowest density layer show the highest
      content of docosahexaenoic acid and sterols, and produce the highest levels of
      reactive oxygen species. The main objective of this study was to determine the
      superoxide dismutase (SOD) content and fatty acid composition of subsets of
      spermatozoa isolated from normozoospermic, asthenozoospermic, and polyzoospermic
      semen samples. Four sperm fractions (1-4) were obtained using ISolate gradient
      centrifugation. Morphology, motion parameters, SOD content, and fatty acid
      composition were assessed in the original samples and their fractions. Overall,
      sperm from normozoospermic samples had higher SOD content than those of
      asthenozoospermic or polyzoospermic samples. Once fractionated in subsets, the
      sperm SOD content decreased significantly (P < 0.0001) from fraction 1 (top) to 4
      (bottom) in all three groups of samples. Fatty acid content as well as the
      oxidation coefficient followed the same pattern, decreasing from fraction 1 to 4
      (F1-F4). Normo- and polyzoospermic samples showed similar amounts of fatty acids,
      while asthenozoospermic samples mostly revealed increased levels. Normozoospermic
      samples displayed the lowest unsaturated fatty acid (UFA)/SOD ratio. Spermatozoa
      from astheno- and polyzoospermic samples, two common seminal pathologies, showed
      higher UFA and lower SOD content than normal sperm, therefore exhibiting a higher
      susceptibility to peroxidative damage. F4 from all groups, containing the most
      mature spermatozoa, displayed the lowest polyunsaturated fatty acid and SOD
      content of all subsets, suggesting that excessive SOD activity as well as
      abundant peroxidative targets may both be deleterious to sperm function.

PMID- 14579419
TI  - Calgizarrin like gene (Cal) deficient mice undergo normal spermatogenesis.
AB  - The murine calgizzarin like gene (Cal) encodes for a calcium binding protein,
      which belongs to the S100 family of EF-hand proteins. It is specifically
      expressed in Sertoli cells in the testis and its expression is down-regulated by
      unknown factor(s) from spermatocytes/spermatids. In this paper, we show by
      transfection of a fusion protein of green fluorescent protein and Cal protein
      into NIH3T3 cells, that the expression of Cal is restricted only in the cytoplasm
      of the cell. A differentially regulated cytoplasmic expression of the Cal in
      Sertoli cells during mouse development suggests that Cal might play an important
      role during spermatogenesis. In order to elucidate the function of the Cal
      protein in the spermatogenesis, we disrupted the Cal locus in mouse by homologous
      recombination. In our knockout mouse, we deleted exon 2 and exon 3 of the Cal
      gene and replaced them with a neomycin cassette, which resulted in a complete
      loss of the Cal transcript. Male and female Cal4+/- and Cal4-/- mice from genetic
      backgrounds C57BL/6J x 129X1/SvJ hybrid and 129X1/SvJ inbred exhibited normal
      phenotype and were fertile. An intensive phenotypic analysis showed no gross
      abnormalities in testis morphology. The lack of the Cal protein also does not
      affect the parameters of sperm, as they are able to fertilize the oocytes in a
      competent manner, which is comparable to wild-type sperm. Collectively our
      results demonstrate that Cal is a nonessential protein and it does not play an
      important role in mouse spermatogenesis or in process of fertilization.

PMID- 14579420
TI  - Repeated exposure to amphetamine disrupts dopaminergic modulation of excitatory
      synaptic plasticity and neurotransmission in nucleus accumbens.
AB  - The mesolimbic dopamine system is essential for reward-seeking behavior, and
      drugs of abuse perturb the normal functioning of this pathway. The nucleus
      accumbens (NAc) is a major terminal field of the mesolimbic dopamine neurons and
      modifications in neuronal structure and function in NAc accompany repeated
      exposure to psychomotor stimulants and other addictive drugs. Glutamatergic
      afferents to the NAc are thought to be crucial to the development of several
      aspects of addictive behavior, including behavioral sensitization and relapse to
      cocaine self-administration. Here we examine glutamatergic neurotransmission and
      synaptic plasticity in NAc neurons in vitro before and after repeated amphetamine
      treatment in vivo. We find that dopamine attenuates the response of NAc neurons
      to repetitive activation of glutamatergic afferents and thereby blocks long-term
      potentiation (LTP) induced by high-frequency afferent stimulation. Dopamine's
      effects are mimicked by dopamine receptor agonists and by amphetamine. In a
      second set of experiments, animals were treated with amphetamine daily for 6 days
      and brain slices were prepared after 8-10 days of withdrawal. In these slices,
      LTP in the NAc appears normal. However, acute exposure of such slices to
      amphetamine no longer modulates synaptic transmission or LTP induction. Thus,
      repeated exposure to amphetamine produces long-lasting changes in the modulation
      of glutamatergic synaptic transmission by amphetamine in the NAc. Our results
      support the notion that after psychostimulant exposure, excitatory synapses on
      NAc neurons alter their response to further psychostimulant for long periods of
      time.

PMID- 14579421
TI  - Functional analysis of MOR-1 splice variants of the mouse mu opioid receptor gene
      Oprm.
AB  - A series of mu opioid receptor gene Oprm splice variants have been reported that
      differ only at their C-terminus. These variants all contain exons 1, 2, and 3 of
      the gene, the exons responsible for coding all seven transmembrane domains.
      Whereas MOR-1 also has exon 4 that encodes for an additional 12 amino acids at
      the tip of the C-terminus, the other MOR-1 variants have unique amino acid
      sequences distinct from those in MOR-1 due to alternative splicing. All these
      variants are mu-selective in binding assays. The current study explored the
      ability of these variants to stimulate [35S]GTPgammaS binding to assess them
      functionally. Only mu opioids stimulated [35S]GTPgammaS binding. Among the mu
      opioids we noted marked differences in their maximal stimulation among the
      clones. This was most prominent with beta-endorphin, which stimulated
      [35S]GTPgammaS binding in the MOR-1E expressing cells to a greater degree than [D
      Ala2,MePhe4,Gly(ol)5]enkephalin (DAMGO; 130%) and was far less effective than
      DAMGO in MOR-1C cells (44%). The rank order of maximal stimulation of the drugs
      varied among the clones as well. Dynorphin A, beta-endorphin and morphine were
      most effective in stimulating [35S]GTPgammaS binding in MOR-1E, while M6G and
      fentanyl were most effective in MOR-1 expressing cells. The potency (EC50) of
      some of the drugs also varied extensively among the clones, with a poor
      correlation between the potency of the drugs to stimulate [35S]GTPgammaS binding
      and their binding affinity. Together, these findings reveal marked functional
      differences among the variants that only can be explained by their structural
      differences at the tip of their C-terminus.

PMID- 14579422
TI  - Effect of the acute and chronic administration of the putative atypical
      antipsychotic drug Y-931 (8-fluoro-12- (4-methylpiperazin-1-yl)-6H
      [1]benzothieno[2,3b][1,5] benzodiazepine maleate) on spontaneously active rat
      midbrain dopamine neurons: an in vivo electrophysiological study.
AB  - This study examined the effect of the p.o. administration of the putative
      atypical antipsychotic drug Y-931 (8-fluoro-12-(4-methylpiperazin-1-yl)-6H
      [1]benzothieno[2,3b][1,5] benzodiazepine maleate) on the activity of
      spontaneously active dopamine (DA) neurons in the ventral tegmental area (VTA)
      and substantia nigra pars compacta (SNC) in anesthetized male Sprague-Dawley
      rats. This was accomplished using in vivo electrophysiology. The acute p.o.
      administration of Y-931 did not significantly alter the number of spontaneously
      active SNC DA neurons compared to vehicle-treated animals. A single p.o.
      administration of 3 and 10 mg/kg of Y-931 significantly increased and decreased,
      respectively, the number of spontaneously active VTA DA neurons compared to
      vehicle-treated animals. The acute administration of 3 mg/kg of Y-931
      significantly altered the firing pattern parameters for all spontaneously active
      SNC DA. The 3 and 10 mg/kg doses of Y-931 significantly increased the degree of
      bursting and irregular activity of spontaneously active VTA and SNC DA neurons
      firing in a bursting pattern. The repeated p.o. administration (21 days) of 1, 3,
      or 10 mg/kg of Y-931 significantly decreased the number of spontaneously active
      VTA DA neurons but had no significant effect on SNC DA neurons compared to
      vehicle-treated animals. The repeated administration of Y-931 did not
      significantly alter the firing pattern of all spontaneously active SNC or VTA DA
      neurons. Our findings indicate that the acute and chronic administration of Y-931
      significantly alters the activity of midbrain DA neurons in rats and the
      electrophysiological profile of chronic Y-931 resembles that of atypical
      antipsychotic agents.

PMID- 14579423
TI  - Oral D-amphetamine causes prolonged displacement of [11C]raclopride as measured
      by PET.
AB  - Parenterally administered D-amphetamine has been used as a challenge drug to
      release dopamine, which in turns inhibits [11C]raclopride binding to dopaminergic
      D2 receptors as measured using positron emission tomography (PET) techniques. The
      primary objective of this study was to determine whether orally administered D
      amphetamine would inhibit [11C]raclopride binding in a manner similar to that
      produced by intravenously administered D-amphetamine. The secondary objective was
      to assess the timeline of these effects. Twelve healthy human volunteers
      participated in this study. Subjects were scanned at baseline and 2 h after D
      amphetamine administration (n = 5); at baseline, 2 and 6 h postdrug (n = 4); or
      at baseline, 2 and 24 h postdrug (n = 3). Orally administered D-amphetamine
      caused a significant decrease in [11C]raclopride binding at 2 h (13% +/- 5%).
      Receptor availability was still decreased at 6 h (18% +/- 6%), even though
      physiological effects had completely returned to baseline. [11C]Raclopride
      binding returned to baseline at 24 h. The percentage of [11C]raclopride
      displacement was not correlated with plasma D-amphetamine concentrations. In
      conclusion, orally administered D-amphetamine caused a reliable and prolonged
      [11C]raclopride displacement, the magnitude of which is similar to that observed
      after intravenous administration. Possible mechanisms for the observed prolonged
      displacement may include persistence of intrasynaptic dopamine and/or receptor
      internalization.

PMID- 14579424
TI  - Differential projections of the infralimbic and prelimbic cortex in the rat.
AB  - The medial prefrontal cortex has been associated with diverse functions including
      attentional processes, visceromotor activity, decision-making, goal-directed
      behavior, and working memory. The present report compares and contrasts
      projections from the infralimbic (IL) and prelimbic (PL) cortices in the rat by
      using the anterograde anatomical tracer, Phaseolus vulgaris-leucoagglutinin. With
      the exception of common projections to parts of the orbitomedial prefrontal
      cortex, olfactory forebrain, and midline thalamus, PL and IL distribute very
      differently throughout the brain. Main projection sites of IL are: 1) the lateral
      septum, bed nucleus of stria terminalis, medial and lateral preoptic nuclei,
      substantia innominata, and endopiriform nuclei of the basal forebrain; 2) the
      medial, basomedial, central, and cortical nuclei of amygdala; 3) the dorsomedial,
      lateral, perifornical, posterior, and supramammillary nuclei of hypothalamus; and
      4) the parabrachial and solitary nuclei of the brainstem. By contrast, PL
      projects at best sparingly to each of these structures. Main projection sites of
      PL are: the agranular insular cortex, claustrum, nucleus accumbens, olfactory
      tubercle, the paraventricular, mediodorsal, and reuniens nuclei of thalamus, the
      capsular part of the central nucleus and the basolateral nucleus of amygdala, and
      the dorsal and median raphe nuclei of the brainstem. As discussed herein, the
      pattern of IL projections is consistent with a role for IL in the control of
      visceral/autonomic activity homologous to the orbitomedial prefrontal cortex of
      primates, whereas those of PL are consistent with a role for PL in limbic
      cognitive functions homologous to the dorsolateral prefrontal cortex of primates.

PMID- 14579425
TI  - Wakefulness-inducing area in the brainstem excites warm-sensitive and inhibits
      cold-sensitive neurons in the medial preoptic area in anesthetized rats.
AB  - Sleep-wakefulness and body temperature are known to influence each other. The
      body temperature rises during wakefulness and falls during sleep. The midbrain
      reticular formation is one of the areas in the brainstem that induces
      wakefulness, while the preoptico-anterior hypothalamic area is the main
      thermoregulatory center in the brain. In order to understand the neural mechanism
      for simultaneous regulation of these functions we hypothesized that the
      wakefulness area in the brainstem is likely to have an opposite influence on warm
      and cold-sensitive neurons in the preoptico-anterior hypothalamic area. Hence,
      first, the wakefulness-inducing area was identified in the brainstem by
      stimulating the site with high-frequency rectangular wave electrical pulses (100
      Hz, 100 microA, 200 microsec for 5-8 sec) in freely behaving chronically prepared
      experimental rats. Then, single neuronal activity from the medial preoptico
      anterior hypothalamic area was recorded and their thermosensitivity was
      established. Thereafter, the influence of such a confirmed wakefulness-inducing
      area in the brainstem on the responsiveness of the single neuronal activity of
      predetermined warm- and cold-sensitive neurons as well as on temperature
      insensitive neurons was studied by overlapping stimulus (1 Hz, 500 microA, 200
      microsec) bound responses. It was observed that the warm-sensitive neurons were
      excited and the cold-sensitive neurons were inhibited by stimulation of the
      wakefulness-inducing area in the brainstem. Most of the temperature-insensitive
      neurons remained unaffected. The results confirm our hypothesis and help in
      understanding the mechanism of simultaneous modulation of body temperature in
      association with changes in wakefulness at the single neuronal level.

PMID- 14579430
TI  - Suzuki reaction takes a "naked hot bath": coupling in high-temperature water
      without transition metals.

PMID- 14579426
TI  - Comparative phenotypic resolution of spontaneous, D2-like and D1-like agonist
      induced orofacial movement topographies in congenic mutants with dopamine D2 vs.
      D3 receptor "knockout".
AB  - Using a novel system, the role of D2-like dopamine receptors in distinct
      topographies of orofacial movement was assessed in mutant mice with congenic D2
      vs. D3 receptor knockout, and compared with findings in D1A mutants. Under
      spontaneous conditions, D2 mutants evidenced increased vertical jaw movements and
      unaltered horizontal jaw movements, with reductions in tongue protrusions and
      incisor chattering; in D3 mutants, only incisor chattering was reduced. Given
      previous evidence that D1A mutants show reduced horizontal but not vertical jaw
      movements, this indicates that apparent oppositional D1-like:D2-like interactions
      in the regulation of composited jaw movements may in fact reflect the independent
      actions of D2 receptors to inhibit vertical jaw movements and of D1A receptors to
      facilitate horizontal jaw movements. Effects of the D2-like agonist RU 24213 to
      exert greater reduction in horizontal than in vertical jaw movements were not
      altered prominently in either D2 or D3 mutants. The D1-like agonists A 68930 and
      SK&F 83959 induced vertical jaw movements, tongue protrusions, and incisor
      chattering; induction of tongue protrusions by A 68930 was reduced in D2 mutants.
      D2 receptors exert topographically specific regulation of orofacial movements in
      a manner distinct from their D1A counterparts, while D3 receptors exert only
      minor regulation of such movements.

PMID- 14579431
TI  - Electrochemical and photochemical control of host-guest complexation at surfaces.
AB  - The application of electrochemistry or photochemistry to modulate supramolecular
      interactions between host-guest systems in solution is a burgeoning field. In
      particular, the speed and reversibility associated with electrochemically or
      photochemically actuated supramolecular interactions has allowed the creation and
      modulation of novel solution-based devices. In recent years, great advances have
      been made in transferring these systems from the solution to the solid state, to
      facilitate the development of molecular-electronics components that can operate
      in unison under the influence of an externally applied stimulus. These studies
      pave the way for the creation of responsive surfaces with advanced materials and
      nanotechnology applications.

PMID- 14579432
TI  - Binding affinities of host-guest, protein-ligand, and protein-transition-state
      complexes.
AB  - The affinities of hosts-ranging from small synthetic cavitands to large proteins
      for organic molecules are well documented. The average association constants for
      the binding of organic molecules by cyclodextrins, synthetic hosts, and albumins
      in water, as well as of catalytic antibodies or enzymes for substrates are
      10(3.5+/-2.5) M(-1). Binding affinities are elevated to 10(8+/-2) M(-1) for the
      complexation of transition states and biological antigens by antibodies or
      inhibitors by enzymes, and to 10(16+/-4) M(-1) for transition states with
      enzymes. The origins of the distributions of association constants observed for
      the broad range of host-guest systems are explored in this Review, and typical
      approaches to compute and analyze host-guest binding in solution are discussed.
      In many classes of complexes a rough correlation is found between the binding
      affinity and the surface area that is buried upon complexation. Enzymes transcend
      this effect and achieve transition-state binding much greater than is expected
      from the surface areas.

PMID- 14579433
TI  - Native electron capture dissociation for the structural characterization of
      noncovalent interactions in native cytochrome C.

PMID- 14579434
TI  - Formation of water clusters in a hydrophobic solvent.

PMID- 14579436
TI  - La2CuS4: A lanthanum copper sulfide with discrete anion triples [S3Cu...S
      S...CuS3]12- based on La4[Cu2S6(S2)].

PMID- 14579435
TI  - Daylight photocatalysis by carbon-modified titanium dioxide.

PMID- 14579437
TI  - Coupling of mechanical and chemical energy: proton affinity as a function of
      external force.

PMID- 14579439
TI  - Synthesis and characterization of dendritic necklaces: a class of outer-sphere
      outer-sphere connected dendronized organoplatinum polymers.

PMID- 14579438
TI  - Expressed enzymatic ligation for the semisynthesis of chemically modified
      proteins.

PMID- 14579440
TI  - Gas-phase reduction of oxides of nitrogen with CO catalyzed by atomic transition
      metal cations.

PMID- 14579441
TI  - Effective modular iminooxazoline (IMOX) ligands for asymmetric catalysis:
      [Zn(IMOX)]-promoted enantioselective reduction of ketones by catecholborane.

PMID- 14579442
TI  - Chloride transport across vesicle and cell membranes by steroid-based receptors.

PMID- 14579444
TI  - Direct oxidation of benzene to phenol with hydrogen peroxide over a modified
      titanium silicalite.

PMID- 14579443
TI  - Label-free detection of DNA hybridization at the nanoscale: a highly sensitive
      and selective approach using atomic-force microscopy.

PMID- 14579445
TI  - A 1-methyl-phosphininium compound: synthesis, X-ray crystal structure, and DFT
      calculations.

PMID- 14579446
TI  - Electrochemistry within a limited number of molecules: delineating the fringe
      between stochastic and statistical behavior.

PMID- 14579447
TI  - The two main DNA lesions 8-Oxo-7,8-dihydroguanine and 2,6-diamino-5-formamido-4
      hydroxypyrimidine exhibit strongly different pairing properties.

PMID- 14579448
TI  - A ruthenium pterin complex showing proton-coupled electron transfer: synthesis
      and characterization.

PMID- 14579450
TI  - Amide from dinitrogen by in situ cleavage and partial hydrogenation promoted by a
      transient zero-valent thorium synthon.

PMID- 14579449
TI  - Organocatalytic asymmetric Michael reaction of cyclic 1,3-dicarbonyl compounds
      and alpha,beta-unsaturated ketones--a highly atom-economic catalytic one-step
      formation of optically active warfarin anticoagulant.

PMID- 14579451
TI  - A concise and flexible total synthesis of (-)-diazonamide A.

PMID- 14579452
TI  - Exceptional redox and photophysical properties of a triply fused diporphyrin-C60
      conjugate: novel scaffolds for multicharge storage in molecular scale
      electronics.

PMID- 14579454
TI  - [The concept of neglected disease].
AB  - "Neglected disease", "neglected population" and more generally "public health
      negligence" are emerging concepts being put forward by numerous humanitarian
      groups. Sleeping sickness provides a typical example to illustrate these
      concepts. After causing a major epidemic in the 1930s, sleeping sickness had been
      practically eradicated by the end of decolonization. Because of more urgent
      priorities, independent national governments relinquished control activities thus
      allowing the disease to return insidiously. By the beginning of the 1990s the
      situation was comparable to that prevailing in 1930 without inciting a response
      commensurate with the extent of the problem. Sleeping sickness is currently not a
      priority and, more simply, is not given proper attention because it affects only
      a few people living in regions presenting little economic interest. This point
      underlines the especially devastating combination of neglected disease and
      neglected population. As early as 1999 the World Health Organization with the
      determined support of Medecins Sans Frontieres launched a campaign not only to
      promote control measures for sleeping sickness at the international level but
      also to use initiatives in the domain to illustrate the enormous potential for
      progress against neglected disease. The effects of this campaign are now
      beginning to be felt.

PMID- 14579455
TI  - [Sleeping sickness: forgotten research?].
AB  - Has research on sleeping sickness, i.e., human African trypanosomiasis (HAT),
      been forgotten? To get an idea on funding, we consulted the Medline bibliographic
      database for the last 14 years. The number of publications on HAT was stagnant
      over the study period. By comparison there was a steady increase in the number of
      publications dealing with malaria. These findings suggest that interest in HAT
      research waned in favor of other endemics even though government or other funding
      agencies continued to finance research networks. To illustrate this situation, we
      present the funding and findings of our multidisciplinary working group in a wide
      range of domains including sleep, endocrine rhythms, identification of biological
      markers, research on physiopathologic mechanisms of the host-pathogen
      relationship, and development on new medications. Over the last 14 years, a total
      of 1 million Euros was spent to produce 68 publications on Medline, i.e., roughly
      15000 [symbol: see text] per publication.

PMID- 14579457
TI  - [Sleeping sickness, forgotten illness: what are the consequences in the field?].
AB  - For nearly 25 years, sleeping sickness was forgotten and increasingly neglected.
      Research programs and control activities against human African trypanosomiasis
      were discontinued. Statistical studies show a constant decrease in the number of
      people screened and cases detected and little change in the ratios of actively
      versus passively diagnosed cases and of the early (blood and lymph involvement)
      versus late (cerebral involvement) stage cases. In the field neglect of the
      disease led to deterioration not only physical facilities but also human
      resources. As teams aged, senior members were often replaced by less than fully
      qualified people resulting in a decline in efficiency and organization. Many
      basic notions were lost and the albeit scarce innovations in diagnosis and
      therapy were often overlooked. When the fight against sleeping sickness was
      finally resumed, these factors had to be taken into account. Efforts in the field
      have been focused on four areas: renovation of equipment, didactic and practical
      training for health care personnel, development of a decision-making algorithm
      based on diagnostic findings, and implementation of new therapeutic protocols.

PMID- 14579456
TI  - [Status of sleeping sickness in 2003].
AB  - On May 3, 2001, the World Health Organization signed a major agreement with the
      pharmaceutical industry for the supply of drugs necessary for treatment of
      sleeping sickness. At that time Dr. Gro Harlem Brutland, director of the WHO,
      announced, "We can now look forward to halting the spread of sleeping
      sickness...". The purpose of this article is to take a look at the situation two
      years later. A first assessment showed that most national programs for the
      control of human African trypanosomiasis (NPCHAT) had practically become
      inoperative. One of the first steps in the new eradication campaign consisted of
      reviving these NPCHAT teams. However this goal could be achieved only insofar as
      awareness of the severity of the disease and of the need to act was felt at every
      level of decision-making. In 2001 the Pan-African Tse-Tse Trypanosomiasis
      Eradication Campaign (PATTEC) initiative was launched by African State leaders to
      promote special attention at the ministerial level, high-level training, and
      international cooperation sometimes involving several NPCHAT teams. Actions in
      the field include trials using new strategies, expert assistance for personnel
      throughout the duration of prospection, and screening and immediate treatment of
      numerous patients in outbreak areas where the disease was thought to be extinct.
      Although progress has not always been measurable in concrete terms, the dynamics
      have shifted almost everywhere.

PMID- 14579458
TI  - [Malaria research for developing countries: the PAL+ program].
AB  - Despite extensive national and international intervention, little progress has
      been made in controlling, malaria and other communicable diseases afflicting many
      developing countries in the world. In response to the need to pursue and enhance
      investigation, the French Ministry of Research launched the PAL+ program in 1999
      with the purpose of promoting concerted "research on malaria and other
      communicable diseases afflicting developing countries". The program is focused on
      developing methods of prevention and treatment for countries in Sub-Saharan
      Africa, Southeast Asia, and Latin America. Advancement of these scientific goals
      is further by a determined efforts (i) to provide means for national coordination
      and scientific organization of malaria research in France and (ii) to revive the
      spirit and mechanisms that characterized previous operations of cooperation
      between France and countries in the southern hemisphere. This new vision of
      cooperation is based on two organizational approaches. The first involves
      integrated programs in which training and transfer of knowledge are essential.
      The second involves joint projects in which networks maintained by a continuous
      exchange in operational seminars contribute to establishing a permanent dialogue
      between the North and South. Priority research areas have been encouraged to
      respond to specific public health issues with emphasis on establishing a balance
      between work in the field and development of knowledge. The priority areas
      include (i) responding to the increasing incidence of drug resistance by
      identifying of new antimalarial drugs and defining new therapeutic strategies;
      (ii) understanding the implications of the pathophysiology and physiopathology
      mechanisms underlying severe malaria manifestations for development of a malaria
      vaccine; (iii) finding new opportunities for prevention of malaria based on more
      effective vector control; (iv) using social anthropology to factor population
      behaviour and habits into the design of effective malaria control measures. The
      PAL+ program was founded on a commitment to provide participating countries with
      the means necessary to improve their research capability and to coordinate and
      structure scientific research by creating enduring partnerships between
      investigators in France and southern hemisphere countries. For this purpose the
      PAL+ workshop program involving regular encounters between northern and southern
      hemisphere researchers has been set up to encourage discussion, interaction, and
      multidisciplinary projects. The exceptionally instructive impact of these
      workshops has proven to be an essential element in the overall PAL+ program that
      has greatly stimulated malaria research. This program has been successful in
      creating a new spirit of intervention and has provided a rarely equalled vehicle
      for collaboration. By bringing the whole research community together over the
      major research programs now under way in the North/South networks, the PAL+
      program represents a new and decisive step in achieving the long-sought goal of
      meaningful scientific cooperation between northern and southern hemisphere
      countries in the domain of public health.

PMID- 14579460
TI  - [Malaria vaccines: state of advancement].

PMID- 14579459
TI  - [Malaria control in the post-genomic era].
AB  - With the publication of seminal articles on the genomic sequence of Plasmodium
      falciparum and P. yoelii yoelii last autumn following the articles on genome of
      Anopheles gambiae, man, and mice, malariology stepped indubitably into a new era.
      A major finding of genome annotation is that nearly 60% of Plasmodium sp. have no
      functional attribution and that a high proportion of P. falciparum sequences have
      no counterpart in P. yoelii. In the light of these findings it will now be
      possible to explore the specificities of the Plasmodium genus and particularities
      of each species--and ultimately the relevance of animal malaria models. Numerous
      avenues of research have been opened not only for drug discovery, vaccine
      development, dissecting the cascade of events contributing to pathology or
      protection, but also for population biology studies and analysis of genetic
      exchanges within field parasite populations. The field has been radically
      changed, and coordinated efforts are needed to implement the powerful post
      genomic technologies. There is an urgent need to exploit this huge mass of new
      data for the development of new control methods. This development requires a
      rational approach of functional genomics and integrative biology. The purpose of
      this article is to briefly summarize current data and discuss experimental
      approaches and perspectives.

PMID- 14579461
TI  - [Systematics and biology of Anopheles vectors of Plasmodium in Africa, recent
      data].
AB  - Renewed interest in research on Plasmodium vectors in Africa and development of
      genetic and molecular biology techniques has been spearheaded by the WHO and the
      PAL+ program of the French research ministry. New findings have led to a better
      understanding of the systematics and biology of the main vector groups. The
      purpose of this article is to describe the newest data on the Anopheles gambiae
      complex and the M and S forms of An. gambiae s.s., on species in the An. funestus
      group and genetic polymorphism of An. funestus, on the two probable species in
      the An. moucheti complex, and on An. mascarenesis.

PMID- 14579462
TI  - [Pathogenesis of cerebral malaria: facts and hypotheses].
AB  - Cerebral malaria (CM) is one of the most serious complications of Plasmodium
      falciparum infection. It is characterized by sequestration of parasitized red
      blood cells (PRBC) in cerebral capillaries and venules. Although the exact cause
      of CM remains unclear, current evidence has clearly implicated metabolic
      disturbances and host immune responses. Studies on mouse CM models suggest the
      involvement of host cells and in particular platelets. These results led us to
      study the role of platelets in human CM. Our findings demonstrated that
      significantly greater accumulation of platelets occurred in capillaries and
      venules of Malawian patients who died from CM than from other diseases. We also
      assessed the role of platelets in cytoadherence of PRBCs using PRBC adhering only
      on CD36, platelets and endothelial cells (EC) constitutively devoid of CD36.
      Cultures using the three components showed that platelets played a role in
      inducing cytoadherence of PRBC on EC via a cellular bridging resistant to
      physiological flow conditions. Having established the link between platelets and
      sequestration, the next step will be to examine the link between platelets and
      CM. A combination of approaches from different disciplines will be needed to gain
      further insight into the mechanisms underlying the complications of malaria.

PMID- 14579463
TI  - [Severe malaria in intensive care units in 2003].
AB  - Malaria requiring intensive care is characterized by failure of one or more organ
      systems and/or development of several metabolic disorders secondary to the
      presence of Plasmodium faliciparum in the blood. Severe imported malaria in non
      immunized adults causes multiple organ failure with variable degrees of altered
      mental status. Acute pulmonary edema is frequent, jaundice associated with mild
      disturbance of liver function is consistent, arterial hypertension due to
      hypovolemia is usual, and acute renal insufficiency is uncommon. Coagulation
      disorders are generally low-grade, acidosis is an unfavorable prognostic factor,
      severe hypoglycemia can occur after the beginning of quinine treatment, and
      anemia is an consistent but discrete symptom. In endemic areas emphasis should be
      placed on the complications of severe malaria in pregnant women due to the high
      incidence of hypoglycemia and pulmonary edema. Severe malaria can develop early
      in children in endemic zones. Presenting signs include cerebral malaria in older
      children and severe anemia in young children. Quinine is the reference treatment
      with a bolus of 17 mg/kg followed by a daily maintenance dose of 24 mg/kg. Use of
      artemether should be restricted to quinine-resistant forms. Total blood exchange
      transfusion is not recommended. Supportive symptomatic treatment, e.g.
      mechanically assisted ventilation and kidney dialysis, is required. In endemic
      zones over 90% of deaths involve children without access to intensive care
      facilities. Mortality rates associated with management of severe imported malaria
      in intensive care range from 10 to 30%.

PMID- 14579464
TI  - [Therapeutic advances against malaria in 2003].
AB  - In tropical areas treatment of uncomplicated Plasmodium falciparum malaria
      episodes is a priority concern. New treatments must be found because of the
      ability of the plasmodium to develop resistance to antimalarial agents. This
      article presents an overview of therapeutic breakthroughs made over the last five
      years. A promising area involves combination therapies using two known or new
      antimalarial agents especially artemisin. Research on antimalarial drugs acting
      by novel mechanisms such as ferroquine, trioxanes, phosphatidyl choline
      inhibitor, fluoroquinolones and fosfidomycine is also reviewed.

PMID- 14579465
TI  - [Health personnel and population aspects of common experience with fever in sub
      Saharan Africa].
AB  - In Sub-Saharan Africa fever is a common experience for the population and health
      care personnel. However widespread use of the term "malaria" by the population,
      paramedical personnel, physicians, etc. leads to the false impression of
      agreement among everyone despite the fact that it is applied to completely
      different concepts. Although the connection between malarial fever and mosquito
      bites is generally understood, it is often weak and unstable. Fever can be
      considered as a normal episode at some stages of pregnancy or childhood
      development. Fever may be attributed to mosquitoes but also to other
      environmental factors. The routine activities of health care personnel in
      frontline health facilities often makes it difficult to adapt practices to new
      guidelines. The relationship between malaria and mosquitoes is determined by a
      whole series of experiences and health messages that the population and health
      care workers must assimilate in the same way. In fact this relation is sometimes
      constructed and reconstructed based on a minimal understanding of medical
      categories. The meeting between the knowledge of the population, physicians, and
      paramedical population often depends on the smallest common denominator (fever =
      malaria) at the intersection of very different experiences.

PMID- 14579466
TI  - [Contribution of social anthropology to malaria control].
AB  - Most countries with endemic malaria have implemented national control programs.
      However there has been practically no change in the burden caused by malaria in
      zones of highest transmission, especially in Africa. Development of forms
      resistant to antimalarial agents suggests that adaptation of the treatment to the
      disease has not been adequately monitored, that insecticide-impregnated bednets
      and screens have not been used sufficiently, and that the vertical approach to
      these problems has destabilized a fragile health care system. Application of
      social anthropology could help to resolve these problems. The five main areas in
      which social anthropology could make a positive contribution can be summarized as
      follows: (1) improving mutual understanding between the population and heath care
      providers by describing popular systems for interpreting the disease; (2)
      describing available care services and popular healing practices as a means of
      understanding the reasoning underlying access to care; (3) analysing the
      implications of recommended preventive measures for social behavior (e.g. "bed
      manners") that must take into account the modalities of appropriation of the
      proposed innovations; (4) improving the relationship between care givers and
      patients by evaluating local moral perceptions; and (5) reducing the adverse
      effects of oververticalization of control programs by promoting opportunities for
      synthesis with projects initiated by community groups and local officials. By
      undertaking work on these problem areas, preliminary and permanent
      pluridisciplinary teams could improve the current situation.

PMID- 14579467
TI  - [Malaria in military personnel: the case of the Ivory Coast in 2002-2003].
AB  - French troops were sent to the Ivory Coast on September 22, 2002 within the
      framework of Operation Unicorn in response to the political unrest. From
      September 22 to October 20, a total of 37 cases of malaria were reported, i.e.,
      35.7 cases per 1000 man-months. As of October 11, the central headquarters of the
      Armed Services Health Corps decided to use doxycycline as the exclusive agent for
      drug prophylaxis in military personnel on duty in the Ivory Coast and to enhance
      vector control measures. The incidence of malaria decreased to 2 cases per 1000
      man-months at the sixth month. A recrudescence of malaria to 15 cases per 1000
      man-months was observed with the rainy season in April. During this period one
      person presenting severe malaria with coma required emergency evacuation to
      France. In May 2003, several studies were undertaken to determine the factors
      that caused this recrudescence. These studies included surveys to evaluate
      awareness concerning malaria and monitor compliance with drug prophylaxis and
      tolerance of doxycycline, a case-control study to identify factors related to
      malarious episodes and an entomological study. Awareness of malaria was high with
      75% of the 477 respondents stating that malaria could be transmitted by single
      mosquito bite. The case-control study showed a correlation between occurrence of
      malarious bouts and non-compliance with drug prophylaxis (p < 10(-5)). The odds
      ratio was 3.05 (95% confidence interval, 1.52-6.14) for subjects claiming zero to
      one incident of non-compliance per week and 7.51 (IC95%, 3.24-17.40) for those
      claiming more than one incident of non-compliance per week. Tolerance of
      doxycyline was good since 72% of respondents reported no adverse effects. The
      main vector was Anopheles gambiae. The number of bites per man per night ranged
      from 25 to 2 and the number of infected bites ranged from 2 to 3 per week.
      Treatment was initiated promptly using quinine at a total dose of 25 mg/kg in 3
      daily doses for 7 days by the intravenous then oral route. This experience shows
      that malaria remains a major concern for military forces, that standardization of
      preventive measures in emergency situations is needed, and that enhanced vector
      control, verification of compliance with drug prophylaxis and prompt treatment
      based on the presence of a physician in each emergency outpost is crucial. These
      recommendation must be applied to all French military personnel in the Ivory
      Coast.

PMID- 14579468
TI  - [Epidemiology of SARS: mission of the emergency medical department of the French
      Hospital of Hanoi].
AB  - During the epidemic of severe acute respiratory syndrome (SARS) that occurred in
      Vietnam in March 2003, the French Ministries of Health and Foreign Affairs
      dispatched a mission composed of personnel from the emergency medical assistance
      department (French acronym, SAMU) and one virologist from the Pasteur Institute
      to the French hospital in Hanoi. The purpose of this mission was to reinforce the
      local medical staff, to bring medical equipment, and to assist in identifying the
      cause of the SARS epidemic. Most of the 39 cases observed involved health care
      personnel working at the hospital. Six including 5 who died presented severe
      manifestations. Application of strict empirical measures of isolation, hygiene,
      and personal protection allowed containment of the SARS outbreak in Hanoi.

PMID- 14579469
TI  - [Outbreak of Ebola hemorrhagic fever in the Republic of the Congo, 2003: a new
      strategy?].
AB  - This article describes the last Ebola haemorrhagic fever (EHF) outbreak that
      occurred in the Cuvette Ouest Region of the Republic of Congo from January to
      April 2003. Epidemiological study demonstrated that the first patient, in whom
      diagnosis was made retrospectively, became ill on December 25, 2002. Subsequently
      until May 7, 2003, a total of 143 cases were recorded in the Mbomo and Kelle
      health districts including 129 fatalities. Thirteen cases were laboratory
      confirmed and 130 were epidemiologically linked. Fifty-three percent of patients
      were male. Age ranged form 5 days to 80 years. Transmission involved direct
      contact with an infected person especially within families. Epidemiological data
      traced introduction of Ebola virus into the population to three primary cases
      mainly involving hunters. In all three cases development of the disease followed
      contact with non-human primates (gorillas) and other mammals (antelope) that had
      either been killed or found dead. Three health care workers were infected during
      the epidemic but nosocomial transmission played a minor role in the epidemic. On
      June 5, the Minister of Health and Population of the Congo Republic officially
      declared that the outbreak of EHF was over in the Cuvette Ouest Region. The last
      case was recorded on April 22 in the small village of Ndjoukou.

PMID- 14579470
TI  - [The Alkhurma virus (family Flaviviridae, genus Flavivirus): an emerging pathogen
      responsible for hemorrhage fever in the Middle East].
AB  - To date tick-borne flaviviruses causing hemorrhagic fevers in humans have been
      isolated in Siberia (Omsk hemorrhagic fever virus), India (Kyasanur Forest
      disease virus), and Saudi Arabia (Akhurma virus). Because of their potential use
      as biological weapons for bioterrorism, these 3 viruses require level 4 biosafety
      handling facilities and have been listed as hypervirulent pathogens by the Center
      for Disease Control and Prevention. Alkhurma virus was isolated in 1995 from
      patients with hemorrhagic fever in Saudi Arabia. Current evidence suggests that
      transmission to humans can occur either transcutaneously either by contamination
      of a skin wound with the blood of an infected vertebrate or bites of an infected
      tick or orally by drinking unpasteurized contaminated milk. To date a total of 24
      symptomatic human cases have been recorded with a mortality rate at 25% (6/24).
      Pauci-symptomatic or asymptomatic cases are likely but epidemiologic data are
      currently unavailable. The complete coding sequence of the prototype strain of
      Alkhurma virus was determined and published in 2001 based on international
      research project involving investigators from France, Great Britain, and Saudi
      Arabia. Phylogenetic studies demonstrate that closest known relative of Alkhurma
      virus is Kyasanur Forest disease virus and that both viruses share a common
      ancestor. Genetic analysis of several human strains sequentially isolated over a
      5-year period showed a very low diversity. This finding has important potential
      implications for diagnosis and vaccination.

PMID- 14579471
TI  - [Hepatitis A virus infection. A review].
AB  - The virus responsible for hepatitis A--hepatitis A virus (HAV)--is a small,
      spherical, and exceptionally resistant RNA-virus. It is transmitted
      preferentially by the faecal-oral route and apparently replicates exclusively in
      the liver. The damage of the liver ensuing from HAV infection most likely does
      not stem directly from virus replication but is the result of an interaction of
      cell mediated virus-specific immunity with infected hepatocytes. Infection is
      usually self limiting, yet, in individual cases may also take a protracted and
      even relapsing course. True chronic infections, however, are not observed. HAV
      has a world-wide distribution. In countries where inadequate sanitary conditions
      prevail, the virus persists in the environment and almost 100% of the population
      acquires infection in childhood. At that age, infection causes no or only minimal
      clinical symptoms. Infected individuals nevertheless develop protective, long
      lasting immunity, probably persisting for entire life. In developed,
      industrialized countries HAV has ceased to circulate in the environment and the
      general population. Here, infections predominantly occur in adults travelling to
      endemic areas or exposed at home to thus infected individuals or members of high
      risk groups (e.g. children in day care centres, i.v. drug users). With increasing
      age infections become more and more clinically manifest and at and beyond of
      adolescence more than 80% of patients develop icteric, in some cases even
      fulminant and fatal hepatitis. Acute hepatitis A infection can be diagnosed by
      demonstrating the presence of anti-HAV-IgM antibodies. Immunity following either
      infection or successful vaccination is assessed by measuring anti-HAV-IgG.
      Preventive measures rely on strict personal and alimentary hygiene as well as on
      vaccination with inactivated (killed) hepatitis A vaccines. These vaccines are
      safe, highly immunogenetic and induce long lasting (> 20 years) protection
      against hepatitis A. Specific antiviral therapy is not yet available.

PMID- 14579472
TI  - [How to plan glucocorticoid withdrawal: diagnostic and therapeutic strategies].
AB  - Glucocorticoids are widely used in medicine and associated with numerous
      complications. Whenever possible, dosage reduction or treatment withdrawal should
      be considered as soon as possible depending on the underlying disease being
      treated. Administration of glucocorticoids induces a physiologic negative feed
      back on the hypothalamic-pituitary-adrenal (HPA) axis and three clinical
      situations can be distinguished during treatment withdrawal: reactivation of the
      disease for which the glucocorticoids were prescribed, acute adrenal
      insufficiency and steroid withdrawal syndrome. Acute adrenal insufficiency is a
      feared complication but probably rare. It is usually seen during stress
      situations and can be observed long after steroid withdrawal. There is no good
      predictive marker to anticipate acute adrenal insufficiency and clinical
      evaluation of the patient remains a key element in its diagnosis. If adrenal
      insufficiency is suspected, HPA suppression can be assessed with dynamic tests.
      During stress situation, steroid administration is then recommended depending on
      the severity of the stress.

PMID- 14579473
TI  - [Meshes for inguinal hernia repair].

PMID- 14579474
TI  - [An unusual IV-expert opinion].

PMID- 14579475
TI  - [Obsessive-compulsive disorders in general practice. How the obsessive-compulsive
      neurotic is revealed by skin and hair].
AB  - Obsessive-compulsive disorder (OCD) is characterized by obsessions, compulsions,
      or both, which cause significant personal distress or social dysfunction. OCD is
      a common psychiatric illness with a prevalence of 1-2%. Because most people have
      regular contact with primary health care services, the patient with OCD is likely
      to see their general practitioner even though psychological problems may not be
      the main reason for consultation. Early recognition of the disorder facilitates
      early intervention. This reduces distress, disability and burden of illness.
      Pharmacological treatment with serotonin reuptake inhibitors (SRI) and cognitive
      behavioral therapy have both been proven to be effective and are evidence based.

PMID- 14579476
TI  - [Panic attacks and panic disorder. Checklist for the diagnosis].
AB  - After looking for possible organic factors, other psychiatric disorders must be
      considered, e.g. depression or other anxiety disorders. With respect of the
      different neurobiologic and psychologic factors of panic attacks the therapy
      should be complex. Psychotherapy (e.g. behavior therapy) and psychopharmacologic
      treatments were proved very well. For the general practitioner the treatment with
      SSRI is very helpful. This approach provides a 60% full remission. For an
      uncomplicated disorder prophylactic treatment is necessary.

PMID- 14579477
TI  - [Might it be epilepsy? What should the genera;l practitioner look out for in
      differential diagnosis].
AB  - Both a missed diagnosis of epilepsy, a wrong diagnosis of epilepsy as something
      else, and a misdiagnosis of something else as epilepsy can have serious
      consequences for the patient, e.g. therapeutic deviations, or physical, physical
      and social complications. Not all possible but some important problems of
      differential diagnosis are discussed, including both typical misdiagnoses of
      epileptic seizures as cardiac synkope or pseudoepileptic fits, oversight of
      subtle manifestions of epilepsy such as absences, juvenile myoclonic epilepsy,
      and isolated auras, and misdiagnoses as epilepsy of migraine variants, syncope,
      episodic ataxias, narcolepsy, and parasomnias.

PMID- 14579478
TI  - [Alzheimer's dementia. Advances in diagnosis and therapy].

PMID- 14579479
TI  - [Memantine brakes Alzheimer's dementia. The NMDA antagonist is effective in
      severe cases, too].

PMID- 14579480
TI  - [Problems with the treatment of schizophrenics in the doctor's office].
AB  - Instead of consulting a psychiatrist, many schizophrenic patients prefer to be
      treated by their family doctor. The present article describes the typical
      problems encountered by family doctors treating such patients, and offers
      practical tips and suggestions. Points of special emphasis are, how to relate to
      acutely ill schizophrenics, depending on the type of schizophrenia presenting
      (maniform-aggressive, delusional or hallucinatory), emergency
      psychopharmacological treatment in acute schizophrenic psychosis, detection of
      emergent schizophrenia as early as possible, local facilities available to help
      the schizophrenic patient.

PMID- 14579482
TI  - [Early diagnosis of alcohol abuse and alcohol dependence in general practice].
AB  - The doctor's office offers the best chance of an early diagnosis of alcohol
      related disorders. The physician can make the most of his opportunity by always
      taking this possibility into account in patients with unspecific symptoms. Since
      so-called low-risk alcohol consumption may develop into damaging drinking and
      finally addictive drinking leading to dependence, the physician must be familiar
      with the features of these different drinking patterns to be able to intervene
      prophylactically in the early forms, and therapeutically in later stages.
      Diagnostic talks with the patient should always contain elements of motivational
      interviewing so as to enable the physician to react appropriately to the degree
      of readiness of the patient to make necessary changes in his lifestyle.

PMID- 14579481
TI  - [Treatment of acute bipolar disorder. Intriguing balancing act between mania and
      depression].
AB  - The term bipolar disorder is no longer limited to the classical manic-depressive
      condition, but now subsumes a wide spectrum of illnesses. As a consequence of
      this expansion of the classification systems, the therapeutic utility of lithium
      and other mood stabilizing agents has to be defined anew. The majority treatment
      recommendations differentiate, symptom-related, between euphoric mania, mixed
      conditions, mania with psychotic symptoms and rapid cycling manic episodes.
      Current acute treatment includes, in addition to lithium, in particular
      carbamazepine and valproate, but also newer antiepileptic drugs such as
      lamotrigine or atypical neuroleptic agents such as olanzapine and risperidone.
      Due to the high suicidal risk, patients with bipolar depression often need to be
      given an antidepressant as well. It must, however, be remembered that in patients
      with rapid cycling, antidepressants may re-trigger mania.

PMID- 14579483
TI  - [Diagnosis and treatment of depressive disorders in the doctor's office].
AB  - Depression is underdiagnosed and undertreated though its high prevalence and life
      threatening character. Once identified, depression can be treated successfully
      with antidepressants, cognitive behavior therapy/interpersonal psychotherapy or a
      combination of both. Regarding selection of a particular antidepressant, newer,
      selective drugs are preferred due to better tolerability and low toxicity.

PMID- 14579484
TI  - [Persisting deficits after severe depression].

PMID- 14579485
TI  - [Current therapy of patients with dementia].
AB  - In recent years, the efficacy of symptomatic treatment in patients with
      Alzheimer's disease has repeatedly been demonstrated in a number of multicenter
      studies. Such treatment aims both to improve the patient's cognitive abilities
      and to preserve his or her quality of life and ability to cope with the
      activities of daily life. In this way the burden on relatives and caregivers is
      reduced, and the need for home or institutionalized care delayed. Causally
      effective therapeutic strategies resulting in a cure or the delaying of
      pathophysiological progression are currently not available, but are being
      investigated in ongoing clinical and experimental studies. Presently available
      treatments should be initiated early on, and applied as long as needed, which
      requires the earliest possible clinical diagnosis by the primary-care physician.
      The results of initial studies reveal an effect of antidementia agents also in
      mixed Alzheimer's and vascular dementia, as well as vascular and lewy-body
      dementia. Efforts to obtain approval for these indications are underway.

PMID- 14579486
TI  - [Algorithms for diagnosis and therapy of sleep disorders in general practice].
AB  - Complaints of insomnia, i.e. problems to fall asleep or maintain asleep and/or
      non-restorative sleep are very common in general practice. This article presents
      the clinical algorithm non-restorative sleep which was devised by the German
      Society for Sleep Research and Sleep Medicine. This algorithm presents a
      guideline for the diagnosis and the treatment of insomnia.

PMID- 14579487
TI  - [Secondary prevention after stroke: healthy life style, oral anticoagulation].
AB  - For patients who suffered a TIA or a stroke the risk of a second event is high.
      The recurrence rate, however, can be significantly reduced by a number of
      prophylactic strategies. Methods for secondary stroke prevention include a
      healthy lifestyle, intensive body exercise, a low cholesterol diet, and the
      cessation of smoking. High levels of blood pressure, cholesterol and blood
      glucose should be rigorously controlled. In particular, blood pressure levels
      should remain below 135/85 mmHg including a physiological day/night profile. All
      patients at high risk for cardiac embolism should receive oral anticoagulants. As
      the risk for embolic events increases with age (especially in patients with
      atrial fibrillation), a rigid "age-cutoff" for anticoagulation is not justified.

PMID- 14579488
TI  - [Current pain therapy in the doctor's office].
AB  - For a modern approach to the treatment of pain, a new form of communication that
      puts emphasis on the need for empathy with the patient is indispensable. On the
      basis of a typical case, the article impressively shows how the general physician
      can focus more sharply on the main problem of dealing with pain. Treatment should
      be applied in accordance with the WHO stepped plan. A basic agreement should help
      to anchor the treatment of pain within the integrated medical care system.

PMID- 14579489
TI  - [Treatment of migraine: analgetic plus antiemetic or tryptan].
AB  - Medical treatment of migraine has the twofold task of cutting short an acute
      attack and preventing further episodes. Mild attacks are treated with analgesics
      and antiemetics. Fixed combination preparations are associated with the risk of
      analgesic-induced headaches and nephropathy and should not be employed. Severe
      attacks are treated with triptanes, depending on a number of features of the
      attack. A "migraine status" requires a special approach. When migraine occurs on
      more than seven days a month, prophylactic measures are indicated with the aim of
      preventing drug-induced headache. The objective is a 50% reduction in the number
      of attacks.

PMID- 14579490
TI  - [Diagnosis and treatment of polyneuropathy: what can the family doctor do?].
AB  - Polyneuropathies are common disorders of the peripheral nervous system. Early
      diagnosis and therapy enables to stop the progression of the polyneuropathy and
      to ameliorate polyneuropathic symptoms in most cases. Clinical examination is
      sufficient to diagnose polyneuropathy. However, to reveal the etiology of a
      polyneuropathy additional diagnostic procedures are necessary. The general
      practitioner should recognize the signs and symptoms of a polyneuropathy and
      start necessary investigations. If the etiology of the polyneuropathy is revealed
      specific therapy can be started. Furthermore, polyneuropathic symptoms can be
      ameliorated independently of the underlying cause.

PMID- 14579491
TI  - [Fast control of manic or mixed episodes. Atypical neuroleptics for bipolar
      patients].

PMID- 14579492
TI  - [Long-term therapy with intuition].

PMID- 14579493
TI  - [Diagnosis and treatment of multiple sclerosis. Update, 2003].
AB  - Multiple sclerosis (MS) is the most common demyelinating disease of the central
      nervous system. The etiology of MS is not yet fully understood. Besides of
      genetic predisposition and environmental factors autoimmune mechanisms seem to
      play a major role in the pathogenesis of MS. Therapy of MS therefore comprises
      mainly immunomodulatory and immuno-suppressive therapeutic concepts. Interferon
      beta (Avonex, Rebif, Betaferon/Betaseron) and Glatirameracetate (Copaxone) offer
      effective therapeutic options for the long-term treatment of relapsing-remitting
      MS. With Mitoxantron (Ralenova) being recently approved by the EMEA for the
      treatment of secondary-progressive and progressive-relapsing MS an effective
      therapeutic option is now available also for this group of patients. The standard
      treatment for acute MS continues to be the intravenous administration of high
      dose methylprednisolone. Several promising new agents (Antegren, Statins) are
      currently under clinical examination and could expand the spectrum of available
      therapeutic strategies soon. Recent and ongoing trials as well as upcoming
      studies on MS therapy are summarized in this review.

PMID- 14579494
TI  - [PRoFESS study presented. Change in secondary prevention].

PMID- 14579495
TI  - [Dipyridamole has therapeutic reserves: inhibition of platelet function and
      more].

PMID- 14579496
TI  - [ASS and dipyridamole combination. A decisive contribution to secondary
      prevention after stroke].

PMID- 14579498
TI  - [Improved pharmacokinetics. Fast tryptan with sustained response].

PMID- 14579497
TI  - [Diagnosis and treatment of Parkinson's syndrome. What is important for the
      general practitioner?].
AB  - The diagnosis of Parkinson's disease (PD) is clinical and is based on the
      identification of a combination of the cardinal motor signs of bradykinesia plus
      at least one of the following: rigidity, tremor or postural instability. There
      are many causes of parkinsonism such as drug induced parkinsonism, subcortical
      vascular disease, and multisystem atrophy. PD is a well characterised syndrome
      which represents only a part of the various causes of parkinsonism. A good
      response to dopaminergics is an important diagnostic criteria for PD.
      Pharmacotherapy for PD relies primarily on levodopa and dopamine agonists. Deep
      brain stimulation is increasingly used in the management of patients with severe
      dopa fluctuations and dyskinesias. Cholinesterase inhibitors are introduced for
      dementia in parkinsonism. Neuroprotective compounds, nerve growth factors such as
      GDNF and the implantation of dopaminergic cells are studied in clinical trials.

PMID- 14579499
TI  - [Highly selective beginning. Associated symptoms and side effects in retrospect].

PMID- 14579500
TI  - [To increase compliance-knowledge. Only every second schizophrenia patient
      remains faithful to the therapy].

PMID- 14579501
TI  - [10 years of interferon treatment in multiple sclerosis. Does the future belong
      to high-dose therapy?].

PMID- 14579502
TI  - [Unclear chronic aches. Often depression plays a part therein].

PMID- 14579503
TI  - [Multiple sclerosis: immunomodulators brake the appearance of "black holes"].

PMID- 14579504
TI  - [More than six billions Euro costs due to illness days. Migraine therapy counts].

PMID- 14579506
TI  - [Child with recently diagnosed epilepsy. Which antiepileptic for first-line
      therapy?].

PMID- 14579505
TI  - [Secondary prevention of ischemic insult and transient cerebral ischemia. Is ASS
      alone enough?].

PMID- 14579507
TI  - [Anti-dementia therapy pays at every stage of the disease. Patients with
      Alzheimer's disease stay all-day fit longer].

PMID- 14579508
TI  - [Many feel sick and of a genuine disease deprived. How should the diagnosis
      "depression" be addressed?].

PMID- 14579509
TI  - Web alert. The chemistry of biological processes.

PMID- 14579510
TI  - Ion channel structures: a review of recent progress.
AB  - Several ion channel structures have recently been determined, including MthK (a
      bacterial K+ channel in an open state), KirBac (a bacterial homolog of mammalian
      inward rectifier K+ channels), KvAP (a bacterial voltage-activated K+ channel)
      and the pore domain of the nicotinic acetylcholine receptor. Analysis of these
      structures has increased our understanding of the molecular mechanisms underlying
      channel gating. A hydrophobic gate appears to operate in a number of channels.
      Structures of ligand binding domains provide some clues as to how ligand-induced
      conformational changes control channel gating, but further experimental and
      computational studies are required before a full picture emerges.

PMID- 14579511
TI  - Modulation of nicotinic acetylcholine receptor function through the outer and
      middle rings of transmembrane domains.
AB  - The photoaffinity labeling of amino acid residues embedded in the lipid bilayer,
      in combination with site-directed mutagenesis and patch-clamp electrophysiology,
      are beginning to delineate a topographic map of lipid-sensitive residues in the
      transmembrane (TM) region of the nicotinic acetylcholine receptor (nAChR), and to
      dissect their contribution to channel gating, opening and closing mechanisms.
      Recent structural data reveal that the TM segments form three concentric layers
      around the ion channel. An inner ring, shaped by five M2 segments (one from each
      subunit) excluded from contact with the lipid, forms the walls of the channel.
      The middle ring is formed by M1 and M3 segments, which exhibit contact with
      lipids, and the M4 membrane-embedded domains constitute an outer ring, distant
      from the channel and loosely separated from the middle ring. Although they are
      not part of the ion conduction pathway, the lipid-exposed middle and outer rings
      significantly modulate nAChR function. Sterols and steroids, in particular, are
      among the ligands that act on this functionally relevant moiety of the nAChR. A
      major challenge for the future is to elucidate the mechanism of propagation of
      information from the lipid-exposed TM rings to the rest of the receptor molecule.

PMID- 14579512
TI  - Hypersensitive knockin mouse strains identify receptors and pathways for nicotine
      action.
AB  - Two series of knockin mouse strains have been constructed with point mutations
      that result in hypersensitive neuronal nicotinic acetylcholine receptors
      containing alpha 4- or alpha 7-subunits. The full expression of the stronger
      alleles produces neonatal excitotoxic lethality; however, mice with attenuated
      expression or milder alleles are viable, and display a range of hypersensitive
      responses to nicotine. To date, measurements have been made on nicotine-induced
      seizures, Straub tail, hypothermia, antinociception, electroencephalograms and
      cellular electrophysiological responses. These strains are helping to define the
      occurrence of these important receptor subtypes, and their role in the acute and
      chronic actions of nicotine. The hypersensitive strains may be useful for the
      development of nicotinic drug therapy.

PMID- 14579513
TI  - Potassium channels as therapeutic targets for autoimmune disorders.
AB  - In human T-lymphocytes, the voltage-gated Kv1.3 channel and the Ca(2+)-activated
      IKCa1 channel play an important role in Ca2+ signaling, activation, adhesion and
      migration and have, therefore, long been regarded as attractive targets for
      immunotherapy. Here, we review the pharmacology of the two channels, their
      expression pattern in naive and memory T-cells and their functional roles during
      T-cell activation, and explain the rationale for the use of Kv1.3 blockers for
      the therapy of T-cell mediated autoimmune diseases.

PMID- 14579514
TI  - The GABAA receptor gene family: new opportunities for drug development.
AB  - gamma-Aminobutyric acid (GABA), which is the main inhibitory neurotransmitter in
      the mammalian brain, exerts its effects through the activation of a ligand-gated
      ion channel, the GABAA receptor, leading to the inhibition of the activity of
      neurons. A family of GABAA receptors has been identified, some of which are
      targets for therapeutic agents such as benzodiazepines, barbiturates and general
      anesthetics. Recently, novel transgenic approaches have been used to understand
      the function of receptor subtypes and, thereby, their therapeutic utility.
      Additionally, progress has been made in the development of novel receptor subtype
      selective compounds. In this review, we will primarily focus on progress achieved
      in the understanding of the function of this receptor family, and potential
      exploitation for drug development.

PMID- 14579515
TI  - The role of nitric oxide in the physiological regulation of Ca2+ cycling.
AB  - The modulation of ion channels, including, but not limited to Ca2+ channels and
      pores, is emerging as a general mechanism by which nitric oxide (NO) exerts
      biological signaling. Due to the fact that the bioactivity of NO involves several
      second messenger systems and is profoundly influenced by multiple environmental
      stimuli, many seemingly divergent observations may be found in the literature.
      Accordingly, there is an ongoing controversy regarding the impact of NO on Ca2+
      channels. An important theme for NO signaling, which may partly settle the
      ongoing controversies regarding NO signaling, is the spatial confinement of NO
      synthases (NOSs) with effector molecules, including ion channels. Perhaps the
      most important environmental stimulus that influences the bioactivity of NO is
      redox milieu, which in turn is influenced by the formation of reactive oxygen
      species and oxygen tension. Here, we review the current knowledge regarding the
      NOS modulation of Ca2+ channels, emphasizing the cardiovascular, musculoskeletal
      and central nervous systems.

PMID- 14579516
TI  - Molecular determinants of high-affinity drug binding to HERG channels.
AB  - Human ether-a-go-go-related gene (HERG) subunits mediate a K+ current that is
      required for normal repolarization of the cardiac action potential. The
      unintentional inhibition of HERG currents by numerous medications results in
      prolongation of the QT interval, as measured on the electrocardiogram, and is
      associated with increased risk of patients suffering from life-threatening
      cardiac arrhythmias. QT interval prolongation is considered a major safety
      concern by worldwide drug regulatory bodies, and early detection of new compounds
      with this undesirable side effect has become an important objective for
      pharmaceutical companies. New studies are shedding light on the structural basis
      of drug binding and the gating-dependent repositioning of key residues in the
      inner cavity of HERG, which are responsible for the unusual sensitivity of HERG
      to pharmacological agents. Insights from these studies may help develop novel
      strategies to reduce the proarrhythmic potential of the next generation of drugs.

PMID- 14579517
TI  - Glycine transporter isoforms in the mammalian central nervous system: structures,
      functions and therapeutic promises.
AB  - The amino acid glycine (Gly) serves as a neurotransmitter at excitatory and
      inhibitory synapses in the mammalian central nervous system. Gly concentrations
      at post-synaptic neurotransmitter receptors are regulated by Na+/Cl(-)-dependent
      Gly transporters, which are expressed in neurons and in glial cells. Recent
      evidence suggests that these transporters are promising targets for the treatment
      of psychiatric and neurological disorders, such as schizophrenia and pain. Here,
      recent research on the structure, regulation and pharmacology of mammalian Gly
      transporters is reviewed.

PMID- 14579518
TI  - Blood-brain barrier genomics and the use of endogenous transporters to cause drug
      penetration into the brain.
AB  - Blood-brain barrier (BBB) genomics enables the rapid discovery of novel
      transporters that are expressed at the brain capillary endothelium. The BBB
      transporters are potential conduits to the brain that therapeutic drugs may use
      to gain passage across the BBB. Due to the small volume of brain occupied by the
      endothelium (10(-3) parts of the brain), it is necessary to build a BBB genomics
      program that is separate from a whole-brain genomics analysis. It is estimated
      that approximately 15% of all genes selectively expressed at the BBB encode for
      transporter proteins, and that only approximately 50% of BBB transporters are
      currently known. The development of a BBB genomics program and the discovery of
      novel BBB transporters could lead to the invention of new approaches to solving
      the BBB drug delivery problem.

PMID- 14579519
TI  - Nuclear hormone receptor co-regulators.
AB  - The critical role of nuclear hormone receptor co-activators in gene expression
      has been extensively studied for the past few years. Co-regulators (co-activators
      and co-repressors) are known to utilize various enzymatic activities, in addition
      to molecular interactions, to modulate gene expression in response to hormonal
      signals. Recent studies that demonstrate the role of co-regulators in cancer and
      developmental disorders have revealed their possible role as targets of therapy.
      A greater understanding of the cellular physiology of co-regulators is necessary
      to explore the pathological ramifications of hormone-dependent diseases, and to
      discover new treatments.

PMID- 14579520
TI  - Androgen receptor and prostate cancer: molecular aspects and gene expression
      profiling.
AB  - Prostate cancer represents a major health problem in the aging population of
      Western countries. Androgen ablation is one of the preferred treatments for this
      disease; unfortunately, relapse is often observed, and no therapeutic agent is
      available at this stage of the disease. Although numerous studies indicate that
      the androgen receptor (AR) remains largely involved at the late stages of the
      disease, the molecular mechanisms responsible for the transition from an androgen
      dependent to an androgen-independent state are still poorly understood. Newly
      discovered aspects of the mode of action of AR, such as cross-talk with other
      signaling pathways, post-translational modifications, interaction with co-factors
      and allosteric modulation by DNA response elements have helped to broaden our
      knowledge on how target gene transcription is regulated. In addition, the gene
      expression profiles recently determined on prostate-derived cell lines and on
      normal and diseased prostate tissues should help to decipher the mechanisms
      leading to uncontrolled growth and metastasis.

PMID- 14579521
TI  - Prospects of memory-modifying drugs that target the CREB pathway.
AB  - The quest to find safe and effective drugs to treat memory disorders and decline
      in humans has been aided by the understanding of the molecules underlying memory
      formation. Studies from vertebrates and invertebrates have identified molecules
      that are specifically required for converting memories into a long-lasting and
      stable form. Due to the fact that the activation of the transcription factor cAMP
      responsive element-binding protein (CREB) is critical for converting short- to
      long-term memory, the molecules required for CREB activation and function are
      potentially important targets for memory-modifying drugs. The progress,
      prospects, challenges and limitations of drugs targeting the CREB pathway are
      reviewed here in the context of molecular mechanisms and the biology of memory.

PMID- 14579522
TI  - Targeting I kappa B kinase for the treatment of inflammatory and other disorders.
AB  - The nuclear transcription factor NF kappa B plays a critical role in the
      pathogenesis of a number of human disorders, particularly those with an
      inflammatory component. Due to the fact that I kappa B kinase (IKK)-catalyzed
      phosphorylation of I kappa B proteins is an essential step in the signal-induced
      activation of NF kappa B, targeting this kinase represents a fascinating
      opportunity to develop novel therapeutics. In this review, the current
      understanding of the role of IKK/NF kappa B in disease processes will be
      discussed, along with evidence demonstrating that IKK inhibitors will be
      efficacious in disorders ranging from rheumatoid arthritis to cancer and
      diabetes. Potential mechanism-based toxicities will also be discussed.

PMID- 14579523
TI  - Novel bone-targeted Src tyrosine kinase inhibitor drug discovery.
AB  - Bone-targeted Src tyrosine kinase (STK) inhibitors have recently been developed
      for the treatment of osteoporosis and cancer-related bone diseases. The concept
      of bone targeting derives from bisphosphonates, and from the evolution of such
      molecules in terms of therapeutic efficacy for the treatment of bone disorders.
      Interestingly, some of the earliest bisphosphonates were recognized for their
      ability to inhibit calcium carbonate precipitation (scaling) by virtue of their
      affinity to chelate calcium. This chelating property was subsequently exploited
      in the development of bisphosphonate analogs as inhibitors of the bone-resorbing
      cells known as osteoclasts, giving rise to breakthrough medicines, such as
      Fosamax (for the treatment of osteoporosis) and Zometa (for the treatment of
      osteoporosis and bone metastases). Relative to these milestone achievements,
      there is a tremendous opportunity to explore beyond the limited chemical space
      (functional group diversity) of such bisphosphonates to design novel bone
      targeting moieties, which may be used to develop other classes of promising small
      molecule drugs affecting different biological pathways. Here, we review studies
      focused on bone-targeted inhibitors of STK, a key enzyme in osteoclast-dependent
      bone resorption. Two strategies are described relative to bone-targeted STK
      inhibitor drug discovery: (i) the development of novel Src homology (SH)-2
      inhibitors incorporating non-hydrolyzable phosphotyrosine mimics and exhibiting
      molecular recognition and bone-targeting properties, leading to the in vivo
      effective lead compound AP-22408; and (ii) the development of novel ATP-based Src
      kinase inhibitors incorporating bone-targeting moieties, leading to the in vivo
      effective lead compound AP-23236. In summary, AP-22408 and AP-23236, which differ
      mechanistically by virtue of blocking Src-dependent non-catalytic or catalytic
      activities in osteoclasts, exemplify ARIAD Pharmaceuticals' structure-based
      design of novel bone-targeted lead compounds, successfully achieving in vivo
      proof-of-concept and providing the framework for the next-generation molecules
      that have further advanced, in terms of preclinical studies, for the treatment of
      osteoporosis and related bone diseases, including osteolytic bone metastases.

PMID- 14579524
TI  - Design strategies for the identification of MMP-13 and Tace inhibitors.
AB  - Inhibitors of matrix metalloprotease (MMP)-13 and tumor necrosis factor-alpha
      converting enzyme (TACE) have been highly sought as potential therapeutic agents
      for the treatment of osteoarthritis and rheumatoid arthritis, respectively. This
      review focuses on the published literature on these inhibitors from 2001 to mid
      2003. Significant advances have been reported in the design and synthesis of
      potent and selective inhibitors of MMP-13 using hydroxamic acid and non
      hydroxamate zinc chelators on a variety of scaffolds. TACE inhibitors based on
      variations of known MMP inhibitors scaffolds and novel designs have been
      reported. Selectivity profiles for these inhibitors range from broad-spectrum to
      TACE-specific. Future clinical studies on these and other inhibitors will
      determine which MMP, or set of MMPs, must be inhibited for efficacy and long-term
      safety.

PMID- 14579525
TI  - Assays to measure the activation of membrane tyrosine kinase receptors: focus on
      cellular methods.
AB  - Many methods have been explored as means to measure the activation and inhibition
      of tyrosine kinase receptors, in vitro using the isolated kinase domain, and in
      living cells. Kinase activity has been measured in enzyme assays using a peptide
      substrate, but with different detection systems. These include the radioactive
      FlashPlate assay, the fluorescent resonance energy transfer (FRET) assay, the
      dissociation-enhance lanthanide fluorescence immunoassay (DELFIA) and other
      formats. These methods have successfully identified inhibitors of receptor
      activity. Cell-based assays have recently emerged to measure receptor activation
      and inhibition. When membrane tyrosine kinase receptors become activated, they
      increase their state of phosphorylation. This phosphorylation may lead to an
      increase in tyrosine kinase-specific activity. Methods have been developed that
      take advantage of these properties. These include measuring the ligand-stimulated
      total tyrosine phosphorylation of the receptor using a DELFIA or an ELISA assay,
      measuring ligand-stimulated enzyme activation of the receptor by quantifying
      enzyme activity, and dimerization of the activated receptor using bioluminescence
      resonance energy transfer (BRET). Although cell-based assays are still in their
      infancy, these techniques may prove a valuable addition to the receptor screening
      strategy.

PMID- 14579526
TI  - Isolation of resistance related-genes to Phytophthora infestans with suppression
      subtractive hybridization in the R-gene-free potato.
AB  - Suppression subtractive hybridization (SSH) was applied in the search of the
      genes induced during the interaction between Phytophthora infestans and
      horizontal resistance potato (R-gene-free). A subtractive library of potato,
      which highly enriches for resistance-related genes to P. infestans, was
      constructed. The potato leaves after inoculating 48 h with mixture of P.
      infestans races were used as "tester" and uninoculated leaves as "control" in the
      experiments. Total 150 of 840 randomly chosen cDNA clones were identified with
      the reveres Northern dot-blot screening method. The sequencing results of 26
      clones indicated that several fragments were previously shown to be activated
      during resistance responses. Seven differentially expressed fragments had
      significant homologous with EST of potato leaves inoculated with P. infestans.
      The sequences of nucleotide or amino acids of partial cDNA fragments shared
      identity with tomato, tobacco and Arabidopsis while four cDNA fragments that had
      no significant homology with EST in GenBank were expected to be new genes
      involved in the disease response.

PMID- 14579527
TI  - [Silica nanoparticles modified as carriers for gene transfection].
AB  - The silica nanoparticles are modified by sodium iodine or sodium chloride with
      different concentration. Their ability to bind and protect plasmid DNA was
      demonstrated by agarose gel electrophoresis. The EGFP-N1 plasmid was transfected
      into HT1080 by combing silica nanoparticle. Eletromicroscope examine revealed
      that nanoparticle-DNA could enter into cells, these silica nanoparticles protect
      DNA against nuclease digestion and the GFP has an effective expression. In
      conclusion, these nanoparticles might be used as DNA carriers for gene
      transfection.

PMID- 14579528
TI  - [Validation of cDNA microarray technology].
AB  - cDNA microarray is a technological approach that has the potential to globally
      measure changes in mRNA expression levels. Self-comparison experiments with the
      same kind of tissue and differential expression experiments with the different
      kinds of tissue have been done to verify the reproducibility and the accuracy of
      this technique. The parameter of the reliability and the reproducibility of the
      microarray data were analyzed by correlation coefficient (R), coefficient of
      variation (CV) and false positive rate (FPR) etc. Meanwhile, the error resource
      also has been inspected. These results showed that generally the correlation
      coefficient of data from this cDNA microarray system was more than 0.9, the
      coefficient of variation was about 15%, and the false positive rate was below 3%.
      The result proves the accuracy of the cDNA microarray data. Consistence rate (CR)
      was advanced here as a new parameter to evaluate the reproducibility of two
      replicate experiments. It has some advantages over correlation coefficient and
      coefficient of variation. The influence of some important factors in the
      experiments, such as different concentration of spotted DNA, mRNA and total RNA,
      different batches of slides and different processes of labeling, have been
      investigated by comparing the results. It was shown that most of the false
      position produced by the experiment system could be reduced by replicate
      experiments.

PMID- 14579529
TI  - [Efficient production of wheat alien translocation lines and characterization by
      molecular cytogenetics].
AB  - The Triticum aestivum-Leymus mollis and T. aestivum-Thinopyrum intermedium
      translocation lines were induced by gametocidal chromosome 3C derived from
      Aegilops triuncialis and gamma-ray irradiated pollens of a T. aestivum-Th.
      intermedium addition line TAI-14 with a lower dosage (10Gy), respectively. By
      genomic in situ hybridization (GISH) analysis, three T. aestivum-L. mollis
      translocation lines (WM-10, WM-43 and WM-47) and three deletion lines (WM-18, WM
      43 and WM-44) were selected from 59 F2 plants derived from a cross combination of
      T. aestivum-L. mollis substitution line M8724-8-13 x T. aestivum-Ae. triunicalis
      3C chromosome addition line. The frequency of translocation lines produced and
      total frequency of chromosome structural variation occurred were 5.08% and 8.47%,
      respectively. Two of the three translocation lines, WM-10 and WM-43 all were
      heterozygous translocation lines carrying one T. aestivum-L. mollis Robertsonian
      translocation chromosome, but the translocation chromosome in the two lines were
      different in morphology. The other one, WM-47 was a double heterozygous
      translocation with two different translocation chromosomes. By the C-banding, one
      of the three translocation lines was identified, the translocation chromosome
      consisted of 7DL of wheat and a chromosome arm of L. mollis. In addition, wheat
      chromosome deletions were observed in some plants. In another cross combination
      involved in common wheat and T. aestivum-Th. intermedium addition line, two alien
      terminal non-Robertsonian translocation lines (WI-21 and WI-68) were identified
      from 69 F2 plants by C-banding and GISH, and the percentage of translocation line
      was 2.90%. By C-banding analysis, the translocation chromosomes involved in wheat
      chromosomes 3A and 4A in the two lines, respectively. These results indicate that
      inducing wheat alien translocation line by gametocidal chromosome and irradiated
      pollens all are efficient methods.

PMID- 14579530
TI  - Approximate estimation of minimal sample size required for marker-assisted
      backcross breeding.
AB  - Backcross breeding is a useful method to transfer favorable alleles from a donor
      parent into a recipient parent. Marker-assisted selection (MAS) can speed up the
      process. To make an appropriate plan before using MAS in a breeding program,
      breeders need to know the minimal sample size of the progeny generation required.
      A method to estimate the minimal sample size required for marker-assisted
      backcross breeding when both foreground selection and background selection are
      conducted is proposed. On the basis of a simplified assumption that the target
      loci are introgressed and the genetic background are independent, the probability
      of selecting individuals with desired genotypes in each generation is
      approximately estimated combining analytical approach (for foreground selection)
      and simulation according to the graphic genotypes of backcrossing parents (for
      background selection). The minimal sample size required to obtain at least one
      desired individual with a given probability is estimated. Application of the
      method is demonstrated with hypothesized examples. The method can be conveniently
      applied to practical backcross breeding programs.

PMID- 14579531
TI  - [Inheritance and segregation of transformants in cotton with two types of insect
      resistant genes].
AB  - A plant expression vector containing a chemeric Bt29K gene coding for the active
      Cry1Ac protein and the arrowhead proteinase inhibition gene API-B was introduced
      into an elite cotton cultivar Jihe 321 by Agrobactertium tumefaciens. Some insect
      resistant cotton lines were developed. Segregation and stabilization of insect
      resistant genes in six transformation lines were studied. Based on the results of
      kanamycin resistant test and insect bioassay using Heliethis armigera, PCR
      detection and Southern-blot, we found that the inheritance and segregation of Bt
      gene were complicated, some transformants were in accordance with Mendelian
      patterns of inheritance in the ratio of insect-resistant plants to non-resistant
      plants in Ti progeny, yet others were non-Mendelian patterns. But the inheritance
      and segregation of Bt gene in homozygous transformation lines were one or two
      pairs of major dominant genes through crossing of insect resistant homozygous
      lines with non-transformation cotton variety. That the insect resistance
      phenotype was conditioned by one or two pairs of dominant genes was ascertained
      in this study. There were two copies of Bt genes in two transformation lines
      DR248 and DR193, which was reported for the first time. The results were
      confirmed by Southern-blot. Through observation of segregation population of
      transgenic plants at different generations, we found that the exogenous Bt gene
      in cotton genome showed unstable in inheritance in early generations, but the
      gene could be stabilized through resistance screening generation by generation.
      The unstability of Bt gene may mean that it need time for the gene to
      compatibilize cotton genome.

PMID- 14579532
TI  - [QTL analysis for percentage of exserted stigma in rice (Oryza sativa L.)].
AB  - Percentage of exserted stigmas (PES) was investigated in Hainan by using a
      population of 127 DH population derived from a cross between a high-PES indica
      variety Zaiyeqing 8 (ZYQ 8) and a low-PES japonica variety Jingxi 17(JX 17) and
      its molecular linkage map of 234 markers. Two QTLs (qPES-2, qPES-3) for PES were
      located on chromosome 2 and 3, respectively. There is no difference between the
      QTLs for single stigma exsertation and total PES, but the only QTL for dual
      stigma exsertation located on chromosome 2, whose positive additive effect was
      from ZYQ 8. Simultaneously the detected QTLs for spikelets per panicle located on
      chromosome 6,8, respectively and had no linkage relation with the QTLs for PES.

PMID- 14579533
TI  - [Screening and genetic analysis of rice glutelin mutant].
AB  - The contribution of rice as a protein source is important. Rice seed protein can
      be divided into four forms, glutelin (57 kDa, 37-39 kDa, 22-23 kDa), prolamine
      (13 kDa), albumin (16 kDa) and globulin (10 kDa, 26 kDa) on its solubility.
      Glutelin is the major storage protein of rice and accounted for 80% of total
      protein found in the rice grain, the mature glutelin comprises an acidic (37-39
      kDa) and an basic subunit (22-23 kDa) coming from a common precursor (57 kDa) by
      post-transcriptional hydrolytic cleavage. Prolamine is the second important. Rice
      seed proteins localize in two types of protein bodies, PB-I, PB-II. PB-I
      containing prolamine is indigestible, whereas PB-II being rich in glutelin is
      digestible. The nutritional value of rice could thus be raised by improving its
      digestible protein glutelin content. On the other hand, the character of low
      digestible protein is also an important target of rice breeding. Low protein rice
      is required for the diet of patients with kidney disease. Three glutelin mutants,
      W3660, W204, W379, were found by screening 168 rice varieties through SDS-PAGE
      analysis of the seeds total proteins. The amounts of 37-39 kDa and 22-23 kDa
      glutelin subunits were much lower and that of 13 kDa prolamine polypeptide was
      higher in W3660 seeds than in ordinary rice; The amounts of 37-39 kDa and 22-23
      kDa glutelin subunits in W204 or W379 seeds were between those in W3660 and
      ordinary rice. Especially, in W379 seed, there was a large quantity of 57 kDa
      polypeptide. For characterizing the genetics of the glutelin mutant, the cross
      population between W3660 and Otorokimochi was constructed. SDS-PAGE analysis of
      the progeny seed total proteins showed, low glutelin content was always
      accompanied by high prolamine content; all F1 seeds had low glutelin and high
      prolamine content; the segregation of low glutelin and normal type in F2 seeds
      was 3:1; the genotypes of F2 plants were deduced by the analysis of F3 seeds, and
      among F2 plants the ratio of homozygotes of low glutelin, heterozygotes of low
      glutelin and homozygotes of normal type was about 1:2:1. These results proved
      that the trait of low glutelin and high prolamine was controlled by a single
      dominant gene and could be inherited by its progeny.

PMID- 14579534
TI  - [Analysis of dominant-recessive mutated character of nfr genes of Chlamydomonas
      reinhardtii and its mutual interaction with the chloroplastic psbA gene].
AB  - Phenotypic analysis of the nfr/Nfr diplontic hybrids has demonstrated the
      recessive mutated character of the nfr genes, and the norflurazon resistant
      character of the Nfr-4 And Nfr-5 mutants were resulted in by the different
      nuclear genes nfr-1 and nfr-2 respectively. From the tetrad analysis result of
      hybridizations of psbA mutant with wild strains CC-124 and nfr mutant, it have
      been demonstrated that the sensitivity of psbA mutated strain to norflurazon
      under photoautotrophic condition is due to its multiple effect whereas the
      chloroplast genome under the mixotrophic situation also gives some effect for
      resistance to norflurazon. From the titration results of cross-resistant
      character for antibiotics of norflurazon resistant strains, we had found that,
      the Nfr-3 mutant has some cross-resistance to erythromycin and streptomycin;
      based on this phenomenon it would be expected that this mutant having resistant
      character to suppressor of phytoene desaturase also give some effect for
      construction of chloroplastic protein.

PMID- 14579535
TI  - [A porcine linkage map of microsatellite markers using a commercial population as
      a reference].
AB  - A commercial population created with 19 hybrid boars [Pietrain x (Pietrain x
      Hampshire)], 52 hybrid sows [Leicoma x (Large White x Landrace)] and their 332
      offspring was used to construct a whole genome porcine linkage map. The genetic
      markers used in this study include 172 microsatellite markers and 3 type- I
      markers (RYR1, PIT1 and PRKAG3). All microsatellite markers were genotyped using
      multiplex PCR reactions and visualized on ABI 377 sequencer. Three type I markers
      were assayed using PCR-RFLP technique. CRIMAP (2.4) analysis revealed a total
      length of the sex-averaged map for SSC1-SSC18 by 2449.2 cM and the length of SSCX
      by 143.1 cM. The average interval distance accounts to 16.3 cM. The
      heterozygosity of the parents at the microsatellite loci averaged 0.70. This map
      will play an important role in screening of QTL for growth, carcass and meat
      quality and reproduction in commercial populations.

PMID- 14579536
TI  - [The developmental patterns of GH-R, IGF-1 and IGF-IR gene expression in adipose
      tissue of Erhualian and large white pigs].
AB  - Growth hormone (GH) is essential for postnatal growth in animal, it regulates
      numerous cellular functions by direct effect on its receptor (GH-R) in many
      different tissues. In present experiment single tube semi-quantitative RT-PCR was
      applied to investigate the developmental patterns of GH-R, IGF-1 and IGF-I R mRNA
      expression in dorsal subcutaneous adipose tissue of Erhualian and Large White
      pigs, and 18S internal standards were used as control. Eight Erhualian pigs were
      sampled at birth, 3, 20, 30, 45, 90, 120, 180 days of age respectively, four
      Large White boars were sampled at 20, 30, 90, 120, 180 days of age respectively.
      The results showed that GH-R mRNA levels in adipose tissue were changed with age
      (P < 0.05). The expression of GH-R mRNA in Erhualian gilts was low at birth but
      reached a peak at 45 days of age, and kept constant thereafter. The expression of
      GH-R mRNA in Erhualian boars was high at birth and reached a peak at 45 day, then
      decreased remarkably. It had no differences between sexes in general. The
      expression of GH-R mRNA in Large White boars was lower than that in Erhualian
      boars (P < 0.01). The IGF-1 mRNA expression in adipose tissue was changed with
      age. The IGF-1 mRNA expression in Erhualian gilts was lower than that in
      Erhualian boars (P < 0.05), and the IGF-1 mRNA expression in Large White boars
      was lower than that in Erhualian boars (P < 0.01). The IGF-I R mRNA expression in
      adipose tissue was changed with aging, but it had no differences between sexes
      and breeds in general. The results suggest that the GH-R, IGF-1 and IGF-I R mRNA
      expression in adipose tissue follow specific developmental pattern, and the
      different patterns of IGF-1 gene expression may contribute to different sediment
      of adipose tissue between two breeds.

PMID- 14579537
TI  - [Analysis of the genomic organization of a novel scorpion toxin BmTXK beta].
AB  - Scorpion venoms contain different types of low molecular mass toxic peptides
      acting on ion channels. Many cDNAs and genomic genes encoding these toxins have
      been isolated and sequenced while the mechanisms of expression and regulation of
      scorpion toxins is not well studied yet. BmTXK beta, one of the four putative
      long-chain potassium channel toxins, is isolated from the cDNA library of the
      venom gland of Chinese scorpion BmK (Buthus martensii Karsch). It has an 886 bp
      intron located in the mature peptide while other scorpion toxins' introns are
      located in the signal peptide. The special genomic organization of BmTXK beta
      makes it a good object to study the mechanism of expression and regulation of
      scorpion toxins. With primers designed according to the already known sequence of
      BmTXK beta, its 5' and 3' flanking regions are cloned by the Vecttorette II
      Staorette Pack method and sequenced. Analysis of the sequence shows that another
      intron longer than 997 bp is located in the signal peptide region of BmTXK beta,
      which makes BmTXK beta different from all the other scorpion toxins that have no
      intron or only one intron in the signal peptide. The special genomic organization
      of BmTXK beta indicates that BmTXK beta is a new membership of long-chain
      potassium channel toxin.

PMID- 14579538
TI  - [Construction of forward and reverse subtracted cDNA libraries between muscle
      tissue of Meishan and Landrace pigs].
AB  - Using suppression subtractive hybridization (SSH) technique, forward and reverse
      subtracted cDNA libraries were constructed between Longissimus muscles from
      Meishan and Landrace pigs. A housekeeping gene, G3PDH, was used to estimate the
      efficiency of subtractive cDNA. In two cDNA libraries, G3PDH was subtracted very
      efficiently at appropriate 2(10) and 2(5) folds, respectively, indicating that
      some differentially expressed genes were also enriched at the same folds and the
      two subtractive cDNA libraries were very successful. A total of 709 and 673
      positive clones were isolated from forward and reverse subtracted cDNA libraries,
      respectively. Analysis of PCR showed that most of all plasmids in the clones
      contained 150-750 bp inserts. The construction of subtractive cDNA libraries
      between muscle tissue from different pig breeds laid solid foundations for
      isolating and identifying the genes determining muscle growth and meat quality,
      which will be important to understand the mechanism of muscle growth,
      determination of meat quality and practice of molecular breeding.

PMID- 14579539
TI  - [Random amplified polymorphic DNA (RAPD) analysis of Drosophila simulans in the
      mainland of China].
AB  - The widespread distribution of Drosophila simulans in the mainland of China was
      found recently. Random amplified polymorphic DNA (RAPD) was used to analyzed DNA
      polymorphisms of 38 Drosophila simulans populations collected from the mainland
      of China. The origins of D. simulans in China were also discussed. Using 40
      arbitary primers (10 bp), we made PCR amplifications under the optimized reaction
      conditions for RAPD that had been established in our laboratory. Our molecular
      phylogenetic tree constructed by UPGMA method showed as follows: (1) 38
      populations are apparently classified into Northern cluster and Southern cluster,
      where NJ(Nanjing) can be considered as the boundary according to latitude. The
      populations in the Northern cluster can be further grouped into two sub-clusters,
      where BJ(Beijing) can be considered as the boundary according to latitude. The
      Northeast one consists of 10 populations, including Mohe(MH), Hailaer(HLR),
      Heihe(HH), Jiamusi(JMS), Haerbin(HRB), Changchun(CC), Shenyang(SY), Dandong(DD),
      Yanji(YJ), Tumen(TM); the other consists of 12 populations, including Beijing
      (BJ), Datong(DT), Huhehaote(HHHT), Yinchun(YC), Xinin(XN), Lanzhou(LZ),
      Taiyuan(TY), Shijiazhuang(SJZ), Yantai (YT), Jinan(JN), Xuzhou(XZ),
      Lianyungang(LYG). The southern cluster consists of the left 16 populations,
      including Zhengzhou (ZZ), Wuhan(WH), Shanghai(SH), Nanjing(NJ), Hangzhou(HZ),
      Chongqing(CQ), Nanchang(NC), Wenzhou(WZ), Changsha (CS), Guiyang(GY), Fuzhou(FZ),
      Kunming(KM), Xiamen(XM), Guangzhou(GZ), Nanning(NN), Hainan(HN). (2) The genetic
      distances among populations relate to the collection sites to a great extent,
      though there are some exceptions. According to the facts that we know, (1) D.
      simulans is an exotic species; (2) The invasion of D. simulans in the mainland of
      China took place in recent 30 years or so. (3) The widespread distribution of D.
      simulans in the mainland of China started in recent 10 years or so. Therefore,
      the results above might not be due to geographical differentiation, but due to
      genetic differences of initial founder individual(s) between geographical
      populations. Some of geographically adjacent populations, however, have common
      initial founder individual(s), which results in the classification of D. simulans
      populations according to their geographical relationship. We suggest that there
      are two possible reasons which result in the genetic differences of initial
      founder individual(s) between geographical populations, one is the D. simulans in
      the mainland of China had multiple origins, the other is founder effect and/or
      bottleneck effect that the D. simulans have experienced in the course of
      expansion.

PMID- 14579540
TI  - [Studies of TGF-beta/Smads expression in lung cancer].
AB  - Smad proteins transduce signals from transforming growth factor beta superfamily
      ligands that regulate cell proliferation, differentiation and death through
      activation of receptor serine/threonine kinases. TGF-beta/Smads signal pathway
      not only has transforming potential but can also drive tumourigenesis, malignant
      progression, invasion and metastasis of human cancers. Using the immuno
      histochemistry, we investigate the expression and location of TGF-beta R II,
      Smad2, Smad4 and Smad7 in 20 lung cancer specimens and 8 lung cancer cell lines.
      The results suggest that aberrant smads protein expression is significantly
      related to lung cancer tumoruigenesis and progression. Interestingly, TGF-beta R
      II and Smad7 strongly express in high metastasis cell lines. High expression of
      TGF-beta R II and smad7 in the cell lines with high-metastatic potential showed a
      conceivable TGF-beta signal pathway independent Smads in the lung cancer, and
      that might mediate invasion and metastasis of lung cancer.

PMID- 14579541
TI  - [Genomic variations in the locus for aminopeptidase N:a putative cellular
      receptor for SARS-CoV spike glycoprotein].
AB  - Aminopeptidase N has been identified as the cellular receptor for human
      coronavirus HCoV-229E and was a putative receptor for the spike glycoprotein
      encoded by the SARS-associated coronavirus (SARS-CoV). We report here
      identification of 9 single nucleotide polymorphisms (SNPs) in ANPEP, encoding
      human aminopeptidase N, in Chinese. All ANPEP exons and their flanking intronic
      sequences were amplified from unrelated normal individuals by polymerase chain
      reaction (PCR) and screened using denaturing high-performance liquid
      chromatography (DHPLC). Nine SNPs were revealed after direct sequencing of PCR
      amplified fragments which showed changes of DHPLC chromatogram. Four of these
      polymorphisms, T321M(962C > T), S651L(1952C > T), S752N(2255G > A) and
      G764R(2290G > A), were non-synonymous; the remaining exonic synonymous and
      intronic ones were T795T(2385C > T), IVS7 + 17G > A, IVS14-16A > G, IVS17 + 12C >
      G and IVS17 + 44C > T. Our data may be useful for studies to investigate the role
      of host genetic factors in SARS pathogenesis, especially for identifying SARS
      susceptible and/or anti-SARS alleles.

PMID- 14579542
TI  - [Progress of miRNA and its functions in eukaryotes].
AB  - Two major kinds of non-coding RNAs play important roles in eukaryotes. One is
      microRNA (miRNA), the other is small interference RNA (siRNA). miRNA, 19-25 nt in
      length, functions in regulation of gene expression and development. Many kinds of
      miRNAs and some proteins assemble in a complex, miRNP, where miRNA gives its
      function, siRNA directs the target mRNA in RNA interference (RNAi). Some distinct
      differences are existed between miRNA and siRNA. The regulation mechanism of
      miRNA may be conserved in eukaryotes.

PMID- 14579543
TI  - Pentachlorophenol poisoning.
AB  - Despite being banned in many countries and having its use severely restricted in
      others, pentachlorophenol (PCP) remains an important pesticide from a
      toxicological perspective. It is a stable and persistent compound. In humans it
      is readily absorbed by ingestion and inhalation but is less well absorbed
      dermally. Its distribution is limited, its metabolism extensive and it is
      eliminated only slowly. Assessment of the toxicity of PCP is confounded by the
      presence of contaminants known to cause effects identical to those attributed to
      PCP. However, severe exposure by any route may result in an acute and
      occasionally fatal illness that bears all the hallmarks of being mediated by
      uncoupling of oxidative phosphorylation. Tachycardia, tachypnoea, sweating,
      altered consciousness, hyperthermia, convulsions and early onset of marked rigor
      (if death occurs) are the most notable features. Pulmonary oedema, intravascular
      haemolysis, pancreatitis, jaundice and acute renal failure have been reported.
      There is no antidote and no adequate data to support the use of repeat-dose oral
      cholestyramine, forced diuresis or urine alkalinisation as effective methods of
      enhancing PCP elimination in poisoned humans. Supportive care and vigorous
      management of hyperthermia should produce a satisfactory outcome. Chronic
      occupational exposure to PCP may produce a syndrome similar to acute systemic
      poisoning, together with conjunctivitis and irritation of the upper respiratory
      and oral mucosae. Long-term exposure has also been reported to result in chronic
      fatigue or neuropsychiatric features in combination with skin infections
      (including chloracne), chronic respiratory symptoms, neuralgic pains in the legs,
      and impaired fertility and hypothyroidism secondary to endocrine disruption. PCP
      is a weak mutagen but the available data for humans are insufficient to classify
      it more strongly than as a probable carcinogen.

PMID- 14579544
TI  - Occupational methaemoglobinaemia. Mechanisms of production, features, diagnosis
      and management including the use of methylene blue.
AB  - Methaemoglobin is formed by oxidation of ferrous (FeII) haem to the ferric
      (FeIII) state and the mechanisms by which this occurs are complex. Most cases are
      due to one of three processes. Firstly, direct oxidation of ferrohaemoglobin,
      which involves the transfer of electrons from ferrous haem to the oxidising
      compound. This mechanism proceeds most readily in the absence of oxygen.
      Secondly, indirect oxidation, a process of co-oxidation which requires
      haemoglobin-bound oxygen and is involved, for example, in nitrite-induced
      methaemoglobinaemia. Thirdly, biotransformation of a chemical to an active
      intermediate that initiates methaemoglobin formation by a variety of mechanisms.
      This is the means by which most aromatic compounds, such as amino- and nitro
      derivatives of benzene, produce methaemoglobin. Methaemoglobinaemia is an
      uncommon occupational occurrence. Aromatic compounds are responsible for most
      cases, their lipophilic nature and volatility facilitating absorption during
      dermal and inhalational exposure, the principal routes implicated in the
      workplace. Methaemoglobinaemia presents clinically with symptoms and signs of
      tissue hypoxia. Concentrations around 80% are life-threatening. Features of
      toxicity may develop over hours or even days when exposure, whether by inhalation
      or repeated skin contact, is to relatively low concentrations of inducing
      chemical(s). Not all features observed in patients with methaemoglobinaemia are
      due to methaemoglobin formation. For example, the intravascular haemolysis caused
      by oxidising chemicals such as chlorates poses more risk to life than the
      methaemoglobinaemia that such chemicals induce. If an occupational history is
      taken, the diagnosis of methaemoglobinaemia should be relatively straightforward.
      In addition, two clinical observations may help: firstly, the victim is often
      less unwell than one would expect from the severity of 'cyanosis' and, secondly,
      the 'cyanosis' is unresponsive to oxygen therapy. Pulse oximetry is unreliable in
      the presence of methaemoglobinaemia. Arterial blood gas analysis is mandatory in
      severe poisoning and reveals normal partial pressures of oxygen (pO2) and carbon
      dioxide (pCO2,), a normal 'calculated' haemoglobin oxygen saturation, an
      increased methaemoglobin concentration and possibly a metabolic acidosis.
      Following decontamination, high-flow oxygen should be given to maximise oxygen
      carriage by remaining ferrous haem. No controlled trial of the efficacy of
      methylene blue has been performed but clinical experience suggests that methylene
      blue can increase the rate of methaemoglobin conversion to haemoglobin some 6
      fold. Patients with features and/or methaemoglobin concentrations of 30-50%,
      should be administered methylene blue 1-2 mg/kg/bodyweight intravenously (the
      dose depending on the severity of the features), whereas those with
      methaemoglobin concentrations exceeding 50% should be given methylene blue 2
      mg/kg intravenously. Symptomatic improvement usually occurs within 30 minutes and
      a second dose of methylene blue will be required in only very severe cases or if
      there is evidence of ongoing methaemoglobin formation. Methylene blue is less
      effective or ineffective in the presence of glucose-6-phosphate dehydrogenase
      deficiency since its antidotal action is dependent on nicotinamide-adenine
      dinucleotide phosphate (NADP+). In addition, methylene blue is most effective in
      intact erythrocytes; efficacy is reduced in the presence of haemolysis. Moreover,
      in the presence of haemolysis, high dose methylene blue (20-30 mg/kg) can itself
      initiate methaemoglobin formation. Supplemental antioxidants such as ascorbic
      acid (vitamin C), N-acetylcysteine and tocopherol (vitamin E) have been used as
      adjuvants or alternatives to methylene blue with no confirmed benefit. Exchange
      transfusion may have a role in the management of severe haemolysis or in G-6-P-D
      deficiency associated with life-threatening methaemoglobinaemia where methylene
      blue is relatively contraindicated.

PMID- 14579545
TI  - Thallium toxicity and the role of Prussian blue in therapy.
AB  - Thallium salts have been used as medicinal agents, as key ingredients in a
      variety of manufacturing processes, and as a potent rodenticide. Additionally,
      environmental concerns are growing, as thallium is a waste product of coal
      combustion and the manufacturing of cement. Thallium salts are rapidly and nearly
      completely absorbed by virtually all routes, with gastrointestinal exposure being
      the most common route to produce toxicity. Thallium enters cells by a unique
      process governed by its similarity in charge and ionic radius to potassium.
      Although the exact mechanism of toxicity has not been established, thallium
      interferes with energy production at essential steps in glycolysis, the Krebs
      cycle, and oxidative phosphorylation. Additional effects include inhibition of
      sodium-potassium-adenosine triphosphatase and binding to sulfhydryl groups. The
      major manifestations of toxicity consist of a rapidly progressive, ascending,
      extremely painful sensory neuropathy and alopecia. Unlike exposure to most metal
      salts, gastrointestinal symptoms of thallium toxicity are relatively minor, and
      constipation is more characteristic than diarrhoea. Many other findings such as
      an autonomic neuropathy, cranial nerve abnormalities, altered mental status,
      motor weakness, cardiac, hepatic, and renal effects are described, but are less
      specific. Thallium also crosses the placenta freely and produces abnormalities in
      animals as well as fetal demise, overt toxicity and congenital abnormalities in
      humans. There are no controlled trials of treatments in thallium-poisoned
      patients. Thus, the literature is predominated by very small animal studies and
      case reports with very limited data. Strong evidence speaks against the use of
      traditional metal chelators such as dimercaprol (British Anti-Lewisite) and
      penicillamine, and the latter may cause redistribution of thallium into the
      central nervous system. Likewise, forced potassium diuresis appears harmful. The
      use of single- or multiple-dose activated charcoal is supported by in vitro
      binding experiments and some animal data, and charcoal haemoperfusion may be a
      useful adjunct. Multiple animal studies give evidence for enhanced elimination
      and improved survival with Prussian blue. Unfortunately, despite the fact that
      many humans have been treated with Prussian blue, the data presented are
      insufficient to comment definitively on its efficacy. However, Prussian blue's
      safety profile is superior to that of other proposed therapies and it should be
      considered the drug of choice in acute thallium poisoning. Public health efforts
      should focus on greater restrictions on access to, and use of, thallium salts.

PMID- 14579546
TI  - Health implications of exposure to environmental nitrogenous compounds.
AB  - All living systems need nitrogen for the production of complex organic molecules,
      such as proteins, nucleic acids, vitamins, hormones and enzymes. Due to the
      intense use of synthetic nitrogen fertilisers and livestock manure in modern day
      agriculture, food (particularly vegetables) and drinking water may contain higher
      concentrations of nitrate than in the past. The mean intake of nitrate per person
      in Europe is about 50-140 mg/day and in the US about 40-100 mg/day. In the
      proximal small intestine, nitrate is rapidly and almost completely absorbed
      (bioavailability at least 92%). In humans, approximately, 25% of the nitrate
      ingested is secreted in saliva, where some 20% (about 5-8% of the nitrate intake)
      is converted to nitrite by commensal bacteria. The nitrite so formed is then
      absorbed primarily in the small intestine. Nitrate may also be synthesised
      endogenously from nitric oxide (especially in case of inflammation), which reacts
      to form nitrite. Normal healthy adults excrete in the urine approximately 62 mg
      nitrate ion/day from endogenous synthesis. Thus, when nitrate intake is low and
      there are no additional exogenous sources (e.g. gastrointestinal infections), the
      endogenous production of nitrate is more important than exogenous sources.
      Nitrate itself is generally regarded nontoxic. Toxicity is usually the result of
      the conversion of nitrate into the more toxic nitrite. There are two major
      toxicological concerns regarding nitrite. First, nitrite may induce
      methaemoglobinaemia, which can result in tissue hypoxia, and possibly death.
      Secondly, nitrite may interact with secondary or N-alkyl-amides to form N-nitroso
      carcinogens. However, epidemiological investigations and human toxicological
      studies have not shown an unequivocal relationship between nitrate intake and the
      risk of cancer. The Joint Expert Committee of the Food and Agriculture
      Organization of the United Nations/World Health Organization (JECFA) and the
      European Commission's Scientific Committee on Food have set an acceptable daily
      intake (ADI) for nitrate of 0-3.7 mg nitrate ion/kg bodyweight; this appears to
      be safe for healthy neonates, children and adults. The same is also true of the
      US Environmental Protection Agency (EPA) Reference Dose (RfD) for nitrate of 1.6
      mg nitrate nitrogen/kg bodyweight per day (equivalent to about 7.0 mg nitrate
      ion/kg bodyweight per day). This opinion is supported by a recent human volunteer
      study in which a single dose of nitrite, equivalent to 15-20 times the ADI for
      nitrate, led to only mild methaemoglobinaemia (up to 12.2%), without other
      serious adverse effects. The JECFA has proposed an ADI for nitrite of 0-0.07 mg
      nitrite ion/kg bodyweight and the EPA has set an RfD of 0.1 mg nitrite
      nitrogen/kg bodyweight per day (equivalent to 0.33 mg nitrite ion/kg bodyweight
      per day). These values are again supported by human volunteer studies.

PMID- 14579547
TI  - Ricin. Mechanisms of cytotoxicity.
AB  - Ricin is a heterodimeric protein produced in the seeds of the castor oil plant
      (Ricinus communis). It is exquisitely potent to mammalian cells, being able to
      fatally disrupt protein synthesis by attacking the Achilles heel of the ribosome.
      For this enzyme to reach its substrate, it must not only negotiate the
      endomembrane system but it must also cross an internal membrane and avoid
      complete degradation without compromising its activity in any way. Cell entry by
      ricin involves a series of steps: (i) binding, via the ricin B chain (RTB), to a
      range of cell surface glycolipids or glycoproteins having beta-1,4-linked
      galactose residues; (ii) uptake into the cell by endocytosis; (iii) entry of the
      toxin into early endosomes; (iv) transfer, by vesicular transport, of ricin from
      early endosomes to the trans-Golgi network; (v) retrograde vesicular transport
      through the Golgi complex to reach the endoplasmic reticulum; (vi) reduction of
      the disulphide bond connecting the ricin A chain (RTA) and the RTB; (vii) partial
      unfolding of the RTA to render it translocationally-competent to cross the
      endoplasmic reticulum (ER) membrane via the Sec61p translocon in a manner similar
      to that followed by misfolded ER proteins that, once recognised, are targeted to
      the ER-associated protein degradation (ERAD) machinery; (viii) avoiding, at least
      in part, ubiquitination that would lead to rapid degradation by cytosolic
      proteasomes immediately after membrane translocation when it is still partially
      unfolded; (ix) refolding into its protease-resistant, biologically active
      conformation; and (x) interaction with the ribosome to catalyse the depurination
      reaction. It is clear that ricin can take advantage of many target cell
      molecules, pathways and processes. It has been reported that a single molecule of
      ricin reaching the cytosol can kill that cell as a consequence of protein
      synthesis inhibition. The ready availability of ricin, coupled to its extreme
      potency when administered intravenously or if inhaled, has identified this
      protein toxin as a potential biological warfare agent. Therapeutically, its
      cytotoxicity has encouraged the use of ricin in 'magic bullets' to specifically
      target and destroy cancer cells, and the unusual intracellular trafficking
      properties of ricin potentially permit its development as a vaccine vector.
      Combining our understanding of the ricin structure with ways to cripple its
      unwanted properties (its enzymatic activity and promotion of vascular leak whilst
      retaining protein stability and important immunodominant epitopes), will also be
      crucial in the development of a long awaited protective vaccine against this
      toxin.

PMID- 14579548
TI  - Ricin poisoning.
AB  - Ricin is a naturally occurring toxin derived from the beans of the castor oil
      plant Ricinus communis. It is considered a potential chemical weapon. Ricin binds
      to cell surface carbohydrates, is internalised then causes cell death by
      inhibiting protein synthesis. Oral absorption is poor and absorption through
      intact skin most unlikely; the most hazardous routes of exposure being inhalation
      and injection. Features of toxicity mainly reflect damage to cells of the
      reticuloendothelial system, with fluid and protein loss, bleeding, oedema and
      impaired cellular defence against endogenous toxins. It has been estimated that
      in man, the lethal dose by inhalation (breathing in solid or liquid particles)
      and injection (into muscle or vein) is approximately 5-10 micrograms/kg, that is
      350-700 micrograms for a 70 kg adult. Death has ensued within hours of deliberate
      subcutaneous injection. Management is supportive. Prophylactic immunisation
      against ricin toxicity is a developing research initiative, although presently
      not a realistic option in a civilian context.

PMID- 14579549
TI  - [Hormone therapy and cardiovascular disease after menopause. Myths and
      realities].

PMID- 14579550
TI  - [Hormone replacement therapy and ischemic heart disease--a dangerous cocktail?
      Changes in the collected evidence].

PMID- 14579551
TI  - [Corticosteroids in palliation of preterminal and terminal cancer patients.
      Evidence or empiricism?].

PMID- 14579552
TI  - [The good rays. About rays: the good, the evil and...].

PMID- 14579553
TI  - [Evaluation of the physiological operability in patients with lung cancer.
      Methods and criteria].

PMID- 14579554
TI  - [Elucidation and treatment of patients with acute chest pain in 16 Danish
      hospitals--the LysAMI project].

PMID- 14579555
TI  - [Laparoscopic ventral hernia repair].

PMID- 14579556
TI  - [Endovascular treatment of ruptured thoracic aorta aneurysm].

PMID- 14579557
TI  - [Poisoning with antidepressive agents].

PMID- 14579558
TI  - [Do we make mountains out of mole hills?].

PMID- 14579559
TI  - [New thinking necessary?].

PMID- 14579560
TI  - [Limits for how much are we prepared to pay for drugs].

PMID- 14579561
TI  - [Misuse of the DSAM name].

PMID- 14579562
TI  - [Debate on common basis of values for psychiatric treatment].

PMID- 14579563
TI  - Structure-function analysis of C-type animal lectins.

PMID- 14579564
TI  - Preparation of recombinant mannan-binding protein with a native oligomeric
      structure.

PMID- 14579565
TI  - Antitumor activity of mannan-binding protein.

PMID- 14579566
TI  - Carbohydrate binding activity of annexin V toward a bisecting N
      acetylglucosamine.

PMID- 14579567
TI  - Recombinant plant lectins and their mutants.

PMID- 14579568
TI  - Psathyrella velutina lectin as a specific probe for N-acetylneuraminic acid in
      glycoconjugates.

PMID- 14579569
TI  - Probing the binding specificity of C-type lectins in vivo.

PMID- 14579570
TI  - Application of a multivalent glycoprobe: characterization of sugar-binding
      specificity of Siglec family proteins.

PMID- 14579571
TI  - Probing for masked and unmasked siglecs on cell surfaces.

PMID- 14579572
TI  - The Man/GalNAc-4-SO4-receptor: relating specificity to function.

PMID- 14579573
TI  - Bacterium-host protein-carbohydrate interactions.

PMID- 14579574
TI  - Design and synthesis of galectin inhibitors.

PMID- 14579575
TI  - RNA interference: analyzing the function of glycoproteins and glycosylating
      proteins in mammalian cells.

PMID- 14579576
TI  - Interaction of glycosphingolipids with signal transducers and membrane proteins
      in glycosphingolipid-enriched microdomains.

PMID- 14579577
TI  - Interaction of the GM2 activator protein with sulfated and sialylated
      glycosphingolipids.

PMID- 14579578
TI  - Differences in recognition of sulfated and sialylated carbohydrate chains.

PMID- 14579579
TI  - Interaction of GM2 activator protein with glycosphingolipids.

PMID- 14579580
TI  - Structural basis for the enzymatic resistance of the GM2 ganglioside.

PMID- 14579581
TI  - Lipid modulation of glycosphingolipid (GSL) receptors: soluble GSL mimics provide
      new probes of GSL receptor function.

PMID- 14579582
TI  - Glycosphingolipid-induced cell signaling: apoptosis.

PMID- 14579583
TI  - Roles of glycosphingolipids in cell signaling: adhesion, migration, and
      proliferation.

PMID- 14579584
TI  - Thin-layer chromatography; immunostaining of glycolipid antigens; and
      interpretation of false-positive findings with acidic lipids.

PMID- 14579585
TI  - Complex gangliosides as cell surface inhibitors for the ecto-NAD+ glycohydrolase
      of CD38.

PMID- 14579586
TI  - Nitrocellulose filter binding to assess binding of glycosaminoglycans to
      proteins.

PMID- 14579587
TI  - Characterization of polysaccharide conformational epitopes by surface plasmon
      resonance.
AB  - SPR techniques can provide a wealth of insight into the nature of protein
      carbohydrate interactions. Information not obtained readily by other
      methodologies can be gathered relatively quickly in a label-free manner with low
      sample consumption. This chapter focused on two applications in which SPR has
      been used to map conformational epitopes on bacterial polysaccharides recognized
      by protective antibodies. In one example, methods for demonstrating the
      conformational nature of the epitope recognized by an anti-GBS antibody were
      described. Dramatic epitopic stabilization at 2 repeating units with further
      significant stabilization between 7 and 20 repeating units was demonstrated. In a
      second example, SPR methods were employed in characterization of the epitope
      recognized by a protective antibody against the group B meningococcus. It was
      shown that the antibody bound a long epitope, in excess of eight monosaccharides
      and probably helical, on NPr-GBMP but did not bind to GBMP. The binding of the
      protective antibody to GBMP only when GBMP is cell associated, or with an
      attached lipid, indicated that the protective GBM epitope consists of more than
      GBMP. NPr-GBMP mimics a cell surface complex consisting of extended helical
      portions of the GBMP in association with a second molecule, possibly a
      phosphoglycerolipid. SPR experiments indicated that the protective nature of
      certain antibodies induced by the NPr-GBMP vaccine is attributable to their
      recognition of an abundant internal epitope on NPr-GBMP and cell-associated GBMP.
      A nonprotective antibody, specific for NPr-GBMP, recognized a terminal and
      consequently minor epitope on the polysaccharide. Low levels of this
      nonprotective antibody binding to cells and unpurified polysaccharide confirmed
      recognition of a minor epitope on the natural antigen as well. In contrast, a
      protective antibody exhibited a high level of binding to the cell-associated
      antigen.

PMID- 14579588
TI  - Study of hyaluronan-binding proteins and receptors using iodinated hyaluronan
      derivatives.
AB  - This chapter detailed methodology for the purification of high molecular weight
      HA, as well as procedures to fragment the HA to prepare large oligosaccharides in
      the range of 40,000-80,000 Da. The aforementioned procedures used to prepare HA
      alkylamine and HA-Bolton-Hunter adducts, as well as 125I-labeled HA, have been
      very reproducible, and the latter preparations are of adequate length to retain
      high-affinity interactions and specific binding, e.g., to human fibrinogen and
      HARE. For example, we were able to isolate, characterize, and clone the rat HARE
      using 125I-labeled HA initially with the dot blot assay to monitor solubilization
      and partial purification, and later with the ligand blot assay, to identify the
      protein after SDS-PAGE. The ligand blot assay enabled us to determine that HARE
      is actually present as two discrete isoreceptors of different molecular masses.
      These techniques should provide a means to analyze purification strategies and to
      characterize additional HA receptors and binding proteins involved in a variety
      of physiologic processes.

PMID- 14579589
TI  - Recognition of glycosaminoglycans by midkine.

PMID- 14579590
TI  - Control of Leishmania-sand fly interactions by polymorphisms in lipophosphoglycan
      structure.

PMID- 14579591
TI  - Use of iodinated hyaluronan derivatives to study hyaluronan binding, endocytosis,
      and metabolism by cultured cells.
AB  - We have described several simple procedures to determine whether cells have
      specific receptors or binding proteins for HA. The advantage of using the
      uniquely modified 125I-labeled HA as a probe is that low levels of binding can be
      detected. It has been straightforward and productive to use 125I-labeled HA to
      quantitate cell surface and intracellular binding sites to determine affinity
      constants for HA binding and to determine whether the cell type being studied can
      efficiently endocytose and degrade the HA. The 125I-labeled HA preparations and
      assays described here and in Chapter 26 provide a very useful array of methods
      for studying the biochemistry and cell biology of HA.

PMID- 14579592
TI  - Carbohydrates as inhibitors of rotaviral infection.

PMID- 14579593
TI  - Cell-based screening of active-site specific chaperone for the treatment of Fabry
      disease.

PMID- 14579594
TI  - Glycosylamidines as potent selective and easily accessible glycosidase inhibitors
      and their application to affinity chromatography.

PMID- 14579595
TI  - Diglycoside-specific glycosidases.

PMID- 14579596
TI  - Use of synthetic oligosaccharide substrate analogs to map the active sites of N
      acetylglucosaminyltransferases I and II.
AB  - Tables III and IV summarize substrate analog data presented in Tables I and II,
      respectively. Data for GlcNAc-T I shown in Tables I and III correlate very well
      with the crystal structure for GlcNAc-T I. This indicates that substitution of
      the various hydroxyl groups by hydrogen, [table: see text] O-methyl, and maybe
      even larger O-alkyl groups does not cause appreciable changes to either the
      overall conformation of the oligosaccharide or the binding mode, thus supporting
      this approach of chemical modification of oligosaccharide substrates for mapping
      of the binding site. There is as yet no crystal structure for GlcNAc-T II. These
      studies indicate both advantages and disadvantages of this approach for
      elucidating the catalytic and binding sites of an enzyme. Substrate analog data
      indicate which chemical groups in the substrate are essential for catalysis and
      binding and suggest the type of linkage involved (hydrogen bond donor or
      acceptor). However, no information has been obtained on the protein groups
      involved in these interactions. If a crystal structure is available, the
      substrate analog conclusions are primarily confirmatory. However, whether or not
      a crystal structure is available, this approach can be very helpful in the design
      of specific inhibitors.

PMID- 14579598
TI  - Recombinant influenza C hemagglutinin-esterase as a probe for sialic acid 9-O
      acetylation.

PMID- 14579597
TI  - Recombinant ganglioside GM2 synthase--expression in insect cells and enzyme
      assay.

PMID- 14579599
TI  - Preparation of recombinant human galectin-1 and use in T-cell death assays.

PMID- 14579600
TI  - Carbohydrate recognition of interleukin-2 in cell proliferation.

PMID- 14579601
TI  - Carbohydrate recognition of vesicular integral protein of 36 kDa (ViP36) in
      intracellular transport of newly synthesized glycoproteins.

PMID- 14579602
TI  - Functions of galectins in cell adhesion and chemotaxis.

PMID- 14579603
TI  - Physical, chemical, antigenic, and immunologic characterization of
      polygalacturonan, its derivatives, and Vi antigen from Salmonella typhi.

PMID- 14579604
TI  - [Comments on the special issues on preventive medicine ].

PMID- 14579605
TI  - [Male infertility].
AB  - In 2/3 of infertility problems, the male partner is, partially or entirely,
      responsible. His investigation starts with a careful history and is followed by a
      thorough physical examination. Then, comes the spermogram. In addition to an
      assessment of the number, motility, and morphology of spermatozoids, this
      examination must involve a spermocytogram, tests of anti-spermatozoid immunity,
      and a bacteriological analysis. The biological study of the seminal plasma is
      also of considerable value. Electron microscopy of sperm is valuable in
      asthenospermic men. A genetic and hormonal investigation is, nowadays, almost
      mandatory in all cases. Testicular biopsy with cryopreservation of testicular
      tissue and demonstration of a possible varicocele can also, in selected cases, be
      of great help. The overall strategy will be decided on the basis of the whole
      investigation.

PMID- 14579606
TI  - [Image of the month. Large thrombus in the right atrium in a patient with acute
      ulcerative colitis].

PMID- 14579607
TI  - [Image of the month. Hematoma of the liver after cardiopulmonary resuscitation].

PMID- 14579608
TI  - [Management of serum magnesium abnormalities].
AB  - Because symptoms associated with hypomagnesia are highly aspecific, this ionic
      abnormality is rarely searched for although it could be present in as much as 20%
      of the population. The mode of correction (oral or intravenous) depends on the
      etiology, severity and clinical consequences of hypomagnesemia. Significant
      hypermagnesemia only occurs in the presence of renal insufficiency and/or acute
      excess administration, mainly by the intravenous route. If interruption of
      administration does not suffice, renal dialysis might become necessary to quickly
      correct the magnesemium serum levels.

PMID- 14579609
TI  - [Clinical case of the month. Rapid atrial fibrillation causing ventricular
      tachycardia and syncope].
AB  - We report a rare case of rapid atrial fibrillation triggering an episode of
      ventricular tachycardia. We review the literature and discuss the potential
      mechanisms of the ventricular arrhythmia.

PMID- 14579610
TI  - [Reversible posterior leukoencephalopathy syndrome].
AB  - Reversible posterior leukoencephalopathy refers to a clinicoradiological syndrome
      observed in patients presenting with acute or subacute symptoms of various
      intensity including seizures, headache, vomiting, confusion and visual
      abnormalities. The radiological features are reversible bilateral white matter
      abnormalities predominantly located in the posterior regions of the cerebral
      hemispheres, demonstrated by computed tomography or, better, by magnetic
      resonance imaging. This syndrome mostly occurs in patients with hypertensive
      encephalopathy or in immunosuppressed patients. The recognition of this syndrome
      is critical as delay in the diagnosis or treatment can result in permanent
      neurological deficit while early prompt control of blood pressure or withdrawal
      of causative drugs can reverse the syndrome.

PMID- 14579611
TI  - [Metabolic syndrome: definitions and epidemiological data].
AB  - The metabolic syndrome is strongly related to visceral obesity and associated
      with a high risk of cardiovascular morbidity and mortality. Since the original
      description of Reaven in 1988, several working definitions have been proposed,
      especially by the World Health Organisation in 1998-99, the National Cholesterol
      Education Program (NCEP-ATP III) Expert Panel in the United States in 2001 and
      the European Group for the Study of Insulin Resistance (EGIR) in 2002. The
      present paper attempts at comparing these various definitions and at reporting
      epidemiological data both in North America and in Europe, especially in Belgium.
      The prevalence is generally higher in men than in women and strongly increases
      with age. Overall, one may estimate that around 20% of adults have a metabolic
      syndrome, which should therefore be considered as an important public health
      problem.

PMID- 14579612
TI  - [A comparative study of the euthanasia laws of Belgium and the Netherlands].
AB  - Recently, laws on euthanasia have been adopted in the Netherlands and Belgium. In
      both countries the legality of euthanasia is conditioned by adherence to strict
      conditions and by confirmation after a notification procedure. Although both laws
      are rather similar, the Belgian law is more fastidious on the requirements of
      prudent practice. The Belgian law does and the Dutch law does not distinguish
      between terminal conditions and non-terminal or slowly evolutive chronic
      conditions. In Belgium, the law only applies to adults, whereas in the
      Netherlands, minors over 12 years of age may under certain conditions receive
      euthanasia. However, the Belgian National Medical Disciplinary Board has recently
      mitigated differences by drafting guidelines which reflect a broad interpretation
      of the law. A major difference between the two countries is that in the Dutch
      society the norm setting on euthanasia developed more through jurisprudence and
      endorsement by the Medical Association than through legislation. We anticipate
      that the implementation of the new law and the notification procedure may be more
      difficult in Belgium than in the Netherlands. In order to promote the quality of
      the euthanasia practice, the euthanasia notification procedure in the Netherlands
      is followed by systematic feedback to the physicians. The strict anonymity of the
      Belgian notification procedure will be broken only when the control commission
      finds some anomaly or deficiency in the declaration. Therefore, unless the
      Evaluation and Control Commission makes ample use of its prerogative to contact
      the physician, the Belgian physicians may be less supported by the notification
      procedure to improve their knowledge and skills in euthanasia.

PMID- 14579613
TI  - [Retrospective evaluation of the carotid endarterectomies performed at CHBAH
      between 1987 and 2001].
AB  - Two broad clinical studies, the ECST and the NASCET, showed that the risk of
      stroke of carotid origin was significantly reduced by surgery if the stenosis was
      superior to 70%, if recent symptoms (less than six months) had occurred and if
      the surgical risk (death or major stroke) was lower than 6%. In the literature
      the rate of major complications varies from 2.3 to 21%. It is consequently
      recommended that in each institution or department the results should be
      evaluated by an independent audit. We studied the 134 carotid
      thromboendarterectomies carried out in the CHBAH between 1987 and 2001. The
      surgical indications were generally strictly respected for symptomatic stenoses
      between 70 and 99%. For asymptomatic stenoses, the indications sometimes
      retrospectively appear arguable but they remain controversial in the literature
      also. We regret the absence of preoperative cerebral imaging in one third of the
      cases. Major complications (death and major stroke) and minor complications (TIA,
      haematoma, infection, headache, cranial nerve injury,...) were respectively 5.2
      and 13.3%, which fits within the recommendations. The Doppler-echo follow-up
      carried out over the last five years shows a rate of restenosis at 70% of 7.9%,
      always asymptomatic.

PMID- 14579614
TI  - [Alcohol, insulin sensitivity and diabetes].
AB  - The relationship between alcohol consumption and insulin resistance shows a U
      shaped curve: insulin resistance is minimal in individuals with regular mild to
      moderate alcohol consumption and increases in both heavy drinkers and subjects
      without any alcohol consumption. These favourable metabolic effects on insulin
      sensitivity of moderate alcohol consumption may explain the significant reduction
      in the development of type 2 diabetes and the risk of cardiovascular
      complications reported in numerous epidemiological studies. This latter effect
      has also reported in patients with diabetes mellitus, although this observation
      remains controversial. However, alcohol consumption could increase the global
      risk of hypoglycaemia, both in the fasting state and after a meal (reactive
      hypoglycaemia) in both diabetic and nondiabetic subjects. These latter effects
      may result from a direct inhibition of gluconeogenesis, from a reduced secretion
      of counterregulatory hormones and/or from an alcohol-induced inappropriate
      behaviour.

PMID- 14579615
TI  - [Numerus clausus at the end of the third year of medical school].
AB  - Owing to the establishment of a procedure aiming at a reduction of the medical
      supply (numerus clausus), the French Community of Belgium had decided to
      introduce, at the end of the third year of medical studies (third candidature), a
      procedure of selective attribution of the certificate allowing for a unlimited
      medical practice. We assessed the predictive value of the results obtained during
      and at the end of the first candidature (first year of medicine) for the
      attribution of this certificate. We studied the results of the 225 students
      enrolled in the first candidature in medicine at the University of Liege during
      the academic year 1997-1998, and we correlated them to the subsequent attribution
      (1999-2000- and 2000-2001) of the certificate. The success of the first
      candidature in the first or second session is an important predicting factor
      towards the reception of the certificate. A non-authorization to continue the
      studies in medicine in case of failure in the first session or a non
      authorization to repeat the first candidature in case of failure in the second
      session would have, respectively, a negative predictive value (NPV) of 91.9% and
      97.4% and would allow to restream 111 students at the end of the first session or
      39 students at the end of the first candidature. The results of the preliminary
      assessments mode during the month of January are also highly predictive of the
      chances to get the certificate. Among the 160 students who have not successfully
      passed a minimum of 3 exams, only 14 students obtained the certificate. The
      restreaming of those students would correspond to a NPV of 91.2%. Students who
      were not successful in a minimum of 2 exams would have less than 5% chance to
      obtain the certificate. In this case, 109 students would be restreamed (NPV =
      95.4%). In conclusion, the selection of the students who will obtain, at the end
      of the third year of medicine, the certificate allowing them for an unlimited
      medical practice is obtained, in a large proportion, during the first candidature
      and especially after the session of January. In view of those results and
      considering the decree abolishing the selection at the end of the third year of
      medical studies, one could argue about the appropriateness of the current
      procedure, chosen by the French Community of Belgium, compared to other solutions
      prioritising an earlier selection of the future doctors.

PMID- 14579616
TI  - [Differential diagnosis of a red nose].
AB  - A red nose is a semiological sign shared in common by a series of diseases. The
      differential diagnosis is important to establish. A careful clinical examination
      often allows to reach the precise diagnosis. A skin biopsy is required when
      erythema is accompanied by a cutaneous infiltration suggesting some granulomatous
      and tumoral processes.

PMID- 14579617
TI  - [Cerebral ischemia].

PMID- 14579618
TI  - [Pathophysiology, etiology and diagnosis of stroke].
AB  - Vascular diseases including stroke increase with advancing age. Their occurrence
      reflects the lifestyle and eating habits of a society. In industrialized
      countries stroke causes a significant loss of DALYs. Each year, approximately 150
      persons per 100,000 inhabitants suffer a stroke. Half a year after the stroke,
      two of three stroke victims are dead or dependent, and all stroke survivors are
      at risk to suffer recurrent strokes. Stroke is due to a focal ischemia. In the
      core of the ischemia blood flow is reduced substantially, mostly to a level below
      the infarction threshold. In the borderzone collaterals can still provide
      sufficient blood to preserve the neurons though the reduced blood flow does not
      suffice for neuronal functioning. This state below functional and above
      infarction threshold is called penumbra. When the stroke signs are recognized
      early and the occluded vessel is recanalized with thrombolytics or mechanically
      the brain tissue in the penumbra can be preserved and the fate of the stroke
      victim is improved compared to spontaneous course. Before administration of
      thrombolytics neurological examination and imaging of the brain using CT or MRI
      are necessary. After stroke, survivors will benefit significantly from secondary
      prevention. In order to perform an individually tailored prevention, additional
      investigations such as neurovascular and cardiac ultrasound, cardiac monitoring
      and blood examinations are necessary to define the cause of the stroke. In
      addition, recognition and modification of individual vascular risk factors are of
      paramount importance.

PMID- 14579619
TI  - [Treatment of acute stroke -- an overview].
AB  - This paper provides an overview on the actual state of acute therapy in patients
      with ischemic stroke. The discussion focusses on intravenous and intraarterial
      thrombolysis, antithrombotic therapy, and the treatment of medical and
      neurological complications, and therapy recommendations are presented. Finally
      ongoing studies, particularly those concerning thrombolysis with glycoprotein
      IIb/IIIa receptor blockers and ultrasound-assisted thrombolysis, are presented.

PMID- 14579620
TI  - [Stroke prevention].
AB  - Life style modification has been shown to reduce stroke risk. In patients with
      risk factors several drugs have proven their efficacy. The most effective
      medications are antihypertensives, antidiabetics, statins and antithrombotics. In
      the prevention of recurrent stroke in patients with a noncardioembolic ischemic
      stroke antiplatelet agents are used. Aspirin or a combination aspirin/dipyridamol
      are the first-line agents. Clopidogrel is recommended for patients with aspirin
      intolerance, several risk factors or recurrent cerebrovascular events. Warfarin
      has demonstrated efficacy in stroke prevention in patients with cardioembolic
      stroke, cerebral venous thrombosis and antiphospholipid antibody syndrome. Other,
      less well established indications for warfarin in the secondary prevention of
      stroke are: symptomatic intracranial artery stenosis; large aortic atheroma and
      extracranial carotid or vertebral artery dissection.

PMID- 14579621
TI  - [Atrial fibrillation and stroke].
AB  - Atrial fibrillation (AF) is the most common cardiac arrhythmia. The prevalence of
      AF is 0.4% in the general population and increases with age up to 6-8% in
      octogenarians. In Switzerland, approximately 68,000 persons are in atrial
      fibrillation, and in the EU countries 3.5 millions. Atrial fibrillation disturbs
      synchronous mechanical atrial activity and impairs the haemodynamics. This can
      give rise to thrombus formation, mostly in the left atrial appendage, and
      embolism to the systemic circulation. Clinical manifestations are most often
      neurological such as transient ischaemic attacks or ischaemic strokes, on average
      5% per year. Of all strokes, one in every six occurs in patients with AF.
      Antiarrhythmic therapy is useful to improve cardiac rate and function in AF.
      However, to reduce first or recurrent emboli, antithrombotic therapy is of
      paramount importance. Adjusted-dose warfarin reduces first or recurrent strokes
      by about 60%. When patients with non-valvular AF are anticoagulated, the odds
      against ischaemic stroke and intracranial bleeding favour an INR between 2.0 and
      3.0. Acetylsalicylic acid is less efficacious than warfarin in AF patients,
      reducing the risk of stroke by about 20%. Therefore, anticoagulation is the
      current treatment modality in AF patients at high or intermediate risk, i.e.
      patients with history of transient ischaemic attack or stroke, those aged > 65
      years, those with a history of hypertension, diabetes, heart failure or
      structural heart disease, valvular disease or significant systolic dysfunction.
      Antiplatelet agents should be used only for young (< 65 years) AF patients at low
      risk.

PMID- 14579622
TI  - [Lacunar infarcts].
AB  - Lacunar infarcts, small deep infarcts resulting from occlusion of a penetrating
      artery, account for about a quarter of all ischemic strokes. The view of lacunar
      infarcts as a benign and rather innocent vascular lesion has been modified during
      the last years. Although the prognosis is more favourable than other subtypes
      during the first years, probably due to the small lesion size, in a longer
      perspective there is an excess risk of death, continual occurrence of recurrent
      stroke, and development of cognitive dysfunction. The risk of recurrent stroke is
      similar to most other types of stroke, and patients are at increased risk to
      develop cognitive decline and dementia. Increasing age, vascular risk factors,
      and high nocturnal blood pressure have significant prognostic implications for
      almost all outcomes. Lacunar infarcts and ischemic white-matter disease, the two
      main types of cerebral small-vessel disease, frequently co-exist and have
      synergistic effects on prognosis and risk of cognitive decline. Antiplatelet
      therapy and risk factor modification are the cornerstones in secondary prevention
      after a lacunar infarct.

PMID- 14579623
TI  - [Subcortical vascular encephalopathy].
AB  - Subcortical Vascular Encephalopathy (SVE) is an increasingly diagnosed disease
      with an enormous socio-economic impact. SVE leads to a progressive disability
      with immobilisation because of gait- and postural disturbances and with a
      progressive subcortical vascular dementia which is composed of cognitive slowing,
      loss of initiative and forgetfulness. A valid diagnosis has become possible only
      through a clear improvement in cerebral imaging techniques developed in the
      eighties. This explains, why so many different and confusing terms exist to
      describe the syndrome. The pathophysiological basis is a cerebral microangiopathy
      leading to lacunar infarcts and to diffuse ischemic white matter lesions, often
      occurring side by side. Taken together, such lesions lead to an interruption of
      parallel functional prefrontal-subcortical circuits, which are essential for
      psychomotor function. Neuroradiological methods like computed tomography (CT) and
      magnetic resonance imaging (MRI) are essential for the diagnosis. The prognosis
      is rather unfavourable. Several consensus meetings have established clinical and
      diagnostic criteria, which can serve as a basis for therapeutical trials. This
      review delineates diagnostic milestones, discusses etiological and
      pathophysiological mechanisms, and displays therapeutical options.

PMID- 14579624
TI  - [Cryptogenic stroke and patent foramen ovale].
AB  - A stroke of unknown etiology is commonly referred to as cryptogenic and is
      diagnosed in a considerable patient population of especially young age. Numerous
      case-control studies revealed a strong and consistent association between
      cryptogenic stroke and the presence of a patent foramen ovale. This relationship
      corroborates paradoxical embolism as likely stroke mechanism in this patient
      population. In approximately twenty-five percent of patients with cryptogenic
      stroke, the patent foramen ovale is accompanied by an atrial septal aneurysm,
      which considerably heightens the risk for recurrent neurological events.
      Therapeutic measures for secondary prevention in this patient population
      encompass medical treatment with antiplatelet agents or anticoagulants and
      surgical or percutaneous closure of patent foramen ovale. Currently, randomised
      clinical studies compare medical treatment with closure of patent foramen ovale
      to determine the most effective treatment strategy in this patient population.

PMID- 14579625
TI  - [Carotid stenosis: diagnosis, patient selection, therapy].
AB  - Atheromatosis frequently develops in the carotid bifurcation, leading to
      significant stenoses of the internal carotid artery. The associated risk of
      stroke reaches 20-25% during the first three years for a high-grade symptomatic
      stenosis and 2-3% per year for a high-grade asymptomatic stenosis. The diagnosis
      of carotid stenosis is made after occurrence of a cerebral ischemic event or
      during an angiologic examination, mainly using Doppler/Duplex-sonography.
      Ultrasonography also enables an accurate determination of the grade of stenosis
      and accordingly the risk of stroke. Non-invasive MR- or CT-angiography is
      presently preferred to digital subtraction angiography to confirm the sonographic
      findings and prepare for an intervention. The intervention has to be decided
      individually for each patient. It is mandatory that the estimated risks of
      operation + best medical therapy be significantly lower than the risks of medical
      therapy alone; otherwise, the benefit of the intervention is lost for the
      patient. Only the mortality and major morbidity are taken into consideration to
      estimate the risks of an intervention. Local and systemic complications are
      transitory and do not influence the final outcome. A high-grade symptomatic
      stenosis (70-99%) should be operated upon whenever possible. A middle-grade
      symptomatic stenosis (50-69%) is treated operatively only if the associated risk
      of stroke is estimated to be high. A high-grade asymptomatic stenosis is operated
      upon only if the estimated perioperative risks are very low (< 3%). A middle
      grade asymptomatic stenosis as well as low-grade stenoses (< 50%) should not be
      operated, but treated with the best medical therapy available. Carotid
      endarterectomy is established as method of first choice to treat a carotid artery
      stenosis. A major complication rate as low as 1% can be expected in experienced
      centres. The long-term results of carotid endarterectomy are well documented and
      the incidence of restenosis is very low. Endovascular angioplasty with stenting
      is increasingly performed as an alternative to the open operation. Presently, the
      scientific evidence is still lacking to recommend this method as primary therapy;
      however, progress in the field is constant and we expect new technical
      improvements which should increase the safety and efficacy of the procedure in
      the near future.

PMID- 14579627
TI  - Reflections on the joys of not existing.

PMID- 14579628
TI  - "For the hatching of our hearts": friendship, pastoral care, and the formation
      for ministry.
AB  - The author explores the notion of friendship by drawing on personal and ministry
      experience, as well as on philosophical and biblical insights, in order to
      suggest a dynamic practice of pastoral care and a process of ministry formation
      which transcends the professional paradigm and the peership principle. He
      suggests that the power to bless, the ability to extend grace, and the potential
      for change are dynamics of friendship which are effective both in pastoral care
      and in ministry formation.

PMID- 14579626
TI  - [Therapeutic interventional neuroradiology in acute stroke].
AB  - Interventional neuroradiological techniques are described, which are used for
      revascularisation of the intra-extracranial vessels in acute stroke. The results
      are based on our experience gained during the endovascular treatment of more than
      300 patients suffering from acute stroke during the last years. Indication,
      procedures and results of intraarterial thrombolysis, thrombo-aspiration,
      percutaneous transluminal angioplasty, and implantation of stents in cases of
      occlusion or pseudoocclusion of brain supplying vessels are discussed.
      Furthermore first experiences with new techniques from other centers are
      presented, e.g., thrombolysis by ultrasound (sonothrombolysis), by angiojet
      aspiration, and laser evaporation of the thromboembolic occlusion of intra- and
      extracranial blood vessels.

PMID- 14579629
TI  - The dignity of servanthood in pastoral care.
AB  - Servanthood is a dominant image of ministry in both Jewish and Christian
      scriptures, and poses a rich source of material from which to address the theme
      of human dignity from the perspective of pastoral care. The biblical concept of
      servanthood, which defines the nature of the pastoral relationship and dignifies
      the personhood of the care recipient, suggests an approach to the issues of
      vulnerability of both giver and receiver of care, and proposes that the caring
      relationship is best conceived as a partnership to which each participant brings
      gifts. The servant theme implies addressing the notion of the kingship of Christ,
      how control issues affect the ministry of pastoral care, and the realization that
      being a servant of the Lord entails a concern for the well being of each
      individual and of the social order; that is, servant ministry mandates both
      visiting the sick (Matthew 25) and seek justice and righteousness as social norms
      (Isaiah 16:5).

PMID- 14579630
TI  - Life review in pastoral counseling: background and efficacy for use with the
      terminally ill.
AB  - Research continues to confirm that sharing one's life story through the process
      of life review enhances psychological well-being and increases life satisfaction.
      Although researchers have outlined techniques and activities that may be used in
      life review with older adults, little work has focused on the use of life review
      methods with terminally ill patients. Additionally, researchers have suggested
      that life review can take on the form of a spiritual assessment; and that such
      spiritually oriented life reviews may enhance a sense of meaning and foster
      reconciliation as one approaches dying. In this article, the authors provide a
      brief review of the research on and the practice of life review. Further, by
      merging concepts of life review with systematic theology, they offer a sample
      instrument--using the example of one faith framework--with which pastoral
      caregivers can better approach the spiritual needs of patients and facilitate a
      less traumatic death in the terminally ill.

PMID- 14579631
TI  - Courage in the development of self in women.
AB  - The author discusses the development of self in women, explores the role of
      courage inherent in this movement, and, employing existentialist notions of
      courage as authenticity, explicates how these notions may lead to the development
      of a stronger sense of self. Notes as well that this development of self entails
      a dangerous complexity and that pastoral care providers will want to aid women in
      holding together both autonomy and connection.

PMID- 14579632
TI  - Spirituality, depression, and loneliness among Jewish seniors residing in New
      York City.
AB  - This article reports the results of research that examined a randomized group of
      118 Jewish seniors who were clients of one of three Jewish social service
      agencies in New York City. They were interviewed by four Clinical Pastoral
      Education residents at the Jewish Institute for Pastoral Care. During the
      interview, participants were asked to respond to the questions contained in the
      Brief Depression Scale, Version 3 of the UCLA Loneliness Scale, and the Index of
      Core Spiritual Experience--INSPIRIT. A statistically significant positive
      correlation was found between the depression and loneliness scores, r(116) = .56,
      p < .001. Spirituality was not correlated with either of these scales. Both
      depression and loneliness were significantly higher among women, among people who
      had physical impairments and those who had been victims of Nazi persecution.
      Depression and loneliness were inversely related to participants' ability to
      venture out of their house and to their relationship with their families. Having
      a sense of meaning or purpose in life was also inversely related to depression
      and loneliness. Spirituality tended to be higher among women, those participants,
      with more years of religious education, and those with physical impairments, but
      only the gender effect was statistically significant.

PMID- 14579633
TI  - Clinical pastoral education and post privacy legislation: an Australian
      perspective.
AB  - Recently introduced privacy legislation in Australia has required that
      professional associations approaching education from the perspective of human
      cases review their standards and develop new policies and procedures to protect
      the privacy of individuals. In this article, the author explores the disruption
      created for Clinical Pastoral Education by the introduction of these privacy
      laws, demonstrates that it is possible to be loyal to both a commitment to
      privacy and learning from "living human documents," develop strategies for
      changing the educational culture, and establish new procedures, strategies, and
      policy.

PMID- 14579634
TI  - The experience of spirituality in the psycho-social adaptation of cancer
      survivors.
AB  - This article presents the results of a retrospective, phenomenological study of
      the experience of spirituality in the psychosocial adaptation of cancer
      survivors. The experience of illness for the participants in the study is one
      which promotes greater personal and spiritual growth. The study demonstrates that
      illness provokes personal growth and transformation in the individual. While
      making use of pre-existing coping resources, the person with cancer reevaluates
      and restructures her or his life, integrating new values, priorities, and
      perspectives which lead the patient to invest her or his life in something
      meaningful and beneficial to others.

PMID- 14579636
TI  - On being a police chaplain.

PMID- 14579635
TI  - Bananas unite!

PMID- 14579637
TI  - The fog lifts.

PMID- 14579638
TI  - The dream and the gift.

PMID- 14579639
TI  - A moment in the life of a SARS chaplain.

PMID- 14579640
TI  - Research on religion and health and professional chaplaincy: a second opinion.

PMID- 14579641
TI  - Trends and shifting ecologies: Part I.
AB  - Ultimately, decreased hospital lengths of stay, endemic shortages of psychiatric
      hospital beds, lengthy waits for indicated outpatient services, and closing of
      residential treatment facilities, safe homes, and detention centers have led to
      what could be viewed as a children's mental health service "de
      institutionalization." Only critical shifts in the underlying philosophy,
      practice, financing, and perceived role of hospital-based child and adolescent
      psychiatric emergency service will put the pediatric emergency department in a
      position to keep up with the accelerating service demands.

PMID- 14579642
TI  - General medical considerations in child and adolescent patients who present with
      psychiatric symptoms.
AB  - This article has presented a 12-step approach to general medical evaluation in
      child and adolescent psychiatric emergencies (Box 2). It is hoped that the
      article, which suggests targeted consideration of key specific issues, will
      stimulate further interest and work in this area and help optimize child
      psychiatrists' ability to exclude general medical conditions and work effectively
      with colleagues in providing children and families with safe medical care.

PMID- 14579643
TI  - Child and adolescent psychiatric emergencies: family psychodynamic issues.
AB  - Given the impact of the family on the etiology, identification, and treatment of
      child mental health problems, this article addresses the role of the family in
      psychiatric emergencies. This article covers relevant aspects of family
      evaluation in an emergency context, factors that determine the family's role in
      disposition, and planning of family considerations in several specific clinical
      emergencies. Improved understanding of the family's contribution leads to a more
      accurate diagnostic consideration and more appropriate disposition
      recommendations. A correct diagnosis and appropriate discharge plan lead to an
      improved prognosis for overall follow-up care and treatment.

PMID- 14579644
TI  - The suicidal child: assessment and management of adolescents after a suicide
      attempt.
AB  - It has been estimated that for each completed suicide, there are 15 to 20
      nonfatal suicide attempts. A prior suicide attempt can create a major elevation
      in the risk of subsequent attempt. A prior suicide attempt also is a strong
      predictor for eventual completed suicide. Consequently, management of an
      adolescent who attempts suicide is important. In this article, the authors
      examine various issues related to suicide risk in adolescents. The article
      focuses on key issues that should be included in a thorough assessment of
      adolescents who are referred for an evaluation during a suicidal crisis. The
      empirical literature is used as a guide for identifying risk factors that should
      be monitored and managed as part of a comprehensive treatment plan.

PMID- 14579646
TI  - The psychotic child.
AB  - Psychosis in children and adolescents is a relatively rare entity, with a
      plethora of possible origins. Appropriate evaluation and treatment can stem only
      from a complete understanding of the differential diagnosis of psychotic
      presentations in children. Once the acute presentation is stabilized and the
      cause for the psychosis accurately identified, the child can be referred
      appropriately to ongoing psychiatric care or substance abuse treatment, or he or
      she can be handed over to another medical specialty to further treat the
      underlying cause when there is a medical cause for the psychosis.

PMID- 14579645
TI  - The aggressive child.
AB  - Acute assessment and management of the aggressive or violent child or adolescent
      are a challenge for clinicians. Early recognition of signs of impending violence
      and a clear understanding of the progression of violent behavior are essential to
      ensure safety of patients and staff. The management of violent and aggressive
      patients using behavioral interventions tailored to the stage of violence or
      aggression is critical to reducing the likelihood that the child or adolescent
      will attack staff or injure self or others. The indications and risks of chemical
      and physical restraints and hospital standards and guidelines that govern the use
      of behavioral and experience regarding the prevalence, presentation, and
      differential diagnosis of psychotic disorders in juveniles. The clinician must
      rapidly disentangle which elements of the clinical presentation indicate true
      psychotic thought processes versus elements that represent misunderstood
      developmentally appropriate phenomena, symptoms of nonpsychotic illnesses, or
      harbingers of an underlying primary medical illness. A thorough assessment is
      required before appropriate treatment can begin.

PMID- 14579647
TI  - The intoxicated child.
AB  - Psychiatric disorders and substance abuse occur frequently together, which leads
      to difficulty in assessment and treatment. An awareness of the prevalence and
      manifestations of psychiatric diagnoses is essential for the quality treatment of
      adolescents who abuse substances. The clinician should keep up-to-date on
      psychopharmacologic interventions [65, 83]. Frequently, the use of psychiatric
      medications, such as antidepressants, mood stabilizers, and psychostimulants, is
      beneficial. Care must be taken, however, to avoid potential interactions between
      the illicit drugs and the prescribed medications [151]. Use of groups such as
      Alcoholics Anonymous, Narcotics Anonymous, or "Double-Trouble" groups, which deal
      with mentally ill and chemical abusing or dual diagnosis issues, often can be a
      useful adjunct to treatment with a mental health professional [152-154]. Careful
      observation, history taking, and appropriate consultation result in better
      detection and treatment of comorbid medical and psychiatric disorders and the
      initial substance abuse problem.

PMID- 14579648
TI  - Cultural considerations in child and adolescent psychiatric emergencies and
      crises.
AB  - The United States is a country of immigrants. With the exception of Native
      Americans, every other American is, or descends from, an immigrant. First- and
      second-generation immigrant children are the most rapidly growing segment of the
      American population. The future of American society is ultimately related to the
      adaptation of these children. Addressing psychiatric emergencies in these
      populations requires attention to their cultural differences and needs.

PMID- 14579649
TI  - Legal considerations in the child psychiatric emergency department.
AB  - Clinicians who practice in the child psychiatric emergency department have the
      complex task of evaluating the mental health or substance abuse needs of
      children, adolescents, and their families during times of crisis. Adding to this
      challenging clinical task are multiple legal considerations with which the
      clinician must be familiar. The precise impact of these legal issues varies from
      state to state. Some of these legal considerations are present at the start of
      the evaluation (consent for evaluation or treatment), during the evaluation
      (psychiatric hospitalization), and at the end of an evaluation (mandatory
      reporting of suspected child abuse and duty to warn or protect third parties from
      harm). Other issues (confidentiality and consent for release of information) are
      present at all stages of the evaluation and continue long after the evaluation
      has been completed. Clinicians who evaluate the psychiatric needs of children and
      adolescents are urged to review their local state laws relating to civil
      commitment, confidentiality, and mandatory reporting.

PMID- 14579650
TI  - The traumatized child at the emergency department.
AB  - The emergency department child and adolescent psychiatrist is in the unique
      position of informing and helping emergency department providers address the
      traumatic impact of the cause of a child's emergency presentation and the
      potential iatrogenic exacerbation of the acute traumatic response. The child and
      adolescent psychiatrist must become a clinical traumatologist who provides the
      necessary consultation and education that lead to practice change in emergency
      department awareness and procedures and performs the optimal evaluation and
      interventions for children who present in psychiatric crisis.

PMID- 14579651
TI  - Trends and shifting ecologies: Part II.
AB  - Community-based systems of care offer some promising ecologically based
      approaches to child psychiatric emergencies. More community-based effectiveness
      research is needed on child and adolescent mental health crisis services. To meet
      the needs of real-world children with serious emotional disorders and their
      families, however, research should include integration of multiple evidence-based
      modalities (such as psychopharmacology, behavioral, and cognitive approaches) and
      the effectiveness of single modalities. Funding priorities in mental health
      systems also should shift significantly to support community-based crisis
      services over more restrictive approaches that have a less solid evidence base.

PMID- 14579652
TI  - Incorrect terminology in nasal anatomy and surgery, suggestions for improvement.
AB  - This article discusses why nomenclature such as 'upper lateral cartilage', 'lower
      lateral cartilage', 'weak triangle', 'empty triangle', 'soft triangle',
      'hemitransfixion', and 'marginal incision' should be abandoned and replaced by
      anatomically, linguistically, and surgically correct terms. Suggestions for
      better terminology are made. The division of the nasal organ into five anatomical
      areas and three physiological parts is questioned. The terms 'interdomal
      ligament', 'intercrural ligament', and 'septocrural ligament' should not be used,
      as histological studies have demonstrated that no such ligaments exist.

PMID- 14579653
TI  - Intranasal electromyography in evaluation of the nasal valve.
AB  - OBJECTIVES: The present study was performed to investigate the best way of using
      surface electromyography (sEMG) in evaluation of muscle involvement in nasal
      valve function. The function of the nasal muscles in nasal valve movements has
      not been investigated sufficiently and in the present study we tried to improve
      the way of testing these muscles introducing the intranasal placement of surface
      EMG electrodes. METHODS: Skin surface electromyography (EMG) and intranasal
      electrode EMG investigation of nasal muscles was performed in two groups (n = 30
      for each Group) of healthy subjects: (1) subjects with extremely effective
      coordination of nasal muscles and (2) those with extremely poor coordination of
      nasal muscles. Functions of the nasal muscles were assessed by EMG in response to
      breathing and voluntary nasal movements. RESULTS: In both Groups, during normal
      breathing all the tested muscles were not active. During forced nasal inspiration
      in Group 1 the transverse nasalis, anomalous nasi, alar nasalis and dilator naris
      anterior were active. In Group 2 during forced nasal inspiration these muscles
      remained inactive. During rhythmic widening of the nostril, the tested nasal
      muscles were active in subjects of Group 1 and significantly less active in Group
      2 (p = 0.0024). In both Groups the amplitude of muscle activity, recorded from
      intranasal electrodes was significantly higher that the amplitude recorded from
      the skin electrodes (p < 0.05). During the tests with two intranasal electrodes,
      the insignificant difference was detected in amplitude between left and right
      nostrils in majority of subjects (Group 1 p = 0.15; Group 2 p = 0.1). CONCLUSION:
      We conclude that in human population the ability to operate nasal muscles is
      varying from person to person, i.e. the nasal muscles can be either inactive
      ("relatively rudimentary") or active. This fact should be taken into account
      before any surgical intervention is planned. The subjects with active nasal
      muscles can control the function of their nasal valve. The intranasal surface EMG
      is a more direct and precise EMG method for nasal valve evaluation in comparison
      to skin surface EMG testing.

PMID- 14579654
TI  - Development of the ETOC: a European test of olfactory capabilities.
AB  - A number of smell tests designed to evaluate human olfactory capabilities have
      been published, but none have been validated cross-culturally. The aim of this
      study was therefore to develop a reliable and quick olfactory test that could be
      used to evaluate efficiently the olfactory abilities of a European population.
      This test, named ETOC and based on a combination of a supra-threshold detection
      task and an identification task, was designed to be a cross-cultural tool that
      would measure the decline in olfactory performance with ageing. Two versions of
      the ETOC, one easy and one less easy, were used to test the olfactory performance
      of European citizens in three countries (France, Sweden and the Netherlands). The
      results indicated that neither version of the ETOC is culture-dependent, and that
      both give scores that well reflect the decrease in olfactory abilities with
      increasing age. A retest session showed that the less easy (and final) version of
      the ETOC is also highly reliable.

PMID- 14579655
TI  - Pressures generated during nose blowing in patients with nasal complaints and
      normal test subjects.
AB  - The authors compared nasal resistance and pressures generated during breathing
      and nose blowing in patients with chronic sinusitis, septal deviations and a
      control group consisting of normal test subjects. The chronic sinusitis group
      generated pressures during nose blowing that were significantly higher (898 daPa
      for the left side and 913 daPa for the right side) than in the other two groups.
      The decongestion didn't change the generated pressures very much. Pressures
      generated during nose blowing with both nostrils closed are much higher than
      pressures generated during nose blowing with one nostril open. These very high
      pressures could have an important role in the pathophysiology of chronic
      sinusitis.

PMID- 14579656
TI  - Effects of dimethindene maleate nasal spray on the quality of life in seasonal
      allergic rhinitis.
AB  - OBJECTIVE: To determine if the H1-receptor antagonist dimethindene maleate (DMM),
      topically applied, is able to improve the quality of life (QoL) in patients with
      seasonal allergic rhinitis better than placebo. METHODS: The study was a multi
      centre, randomised, placebo-controlled, double-blinded phase III trial including
      157 patients. Two parallel groups received either DMM nasal spray or placebo for
      2 weeks. Patients answered 5 QoL questionnaires (Rhinoconjunctivitis QoL
      Questionnaire (LQ-AR), Munich Life Dimension List (MLDL), Profile of Mood States
      (POMS), 2 Visual Analogue Scales (VAS-QoL, VAS-GES)) on days 1, 4, 8, and 15.
      RESULTS: QoL improved significantly in all scales and groups. Statistically
      significant differences between groups were achieved in the sub-scales LQ-AR Eye
      Symptoms and Daily Activities, MLDL Total, POMS Depression and Energy, VAS-QoL
      and VAS-General Health. All differences favoured the DMM group and were present
      initially but disappeared in visit 4, except MLDL Total and POMS Energy. Almost
      all other scores had a better tendency of DMM. CONCLUSION: A significant
      improvement of QoL was found in both groups. Only weak differences between groups
      (in favour of DMM) were found. There are several reasons explaining this outcome,
      mainly the rainy weather during the study period (mean weather index 10-20% less
      sunny than in previous seasons).

PMID- 14579657
TI  - Oxymetazoline nasal spray three times daily for four weeks in normal subjects is
      not associated with rebound congestion or tachyphylaxis.
AB  - Topical decongestants are available over the counter and provide rapid relief of
      nasal obstruction for conditions of short duration, for example the common cold.
      Manufacturers' recommendations are that topical decongestants should not be used
      regularly for more than 1 week in view of the risk of rebound mucosal hyperaemia
      with persistent nasal obstruction and refractoriness to further effects of
      decongestants. For this reason we performed a randomised double-blind placebo
      controlled trial in 30 normal adult subjects with 0.05% oxymetazoline nasal spray
      2 sprays (0.1 ml/spray) to each nostril 3 times daily over an extended period of
      4 weeks. Degree of nasal blockage was assessed before and after 4 weeks treatment
      and for 2 weeks following discontinuation of treatment. Outcome measures included
      diary symptom scores and measurements of nasal peak inspiratory flow, airway
      resistance (using posterior active rhinomanometry) and volume (using acoustic
      rhinometry). Nasal patency was assessed at baseline and 15 minutes after
      oxymetazoline challenge at each clinic visit. Results demonstrated no significant
      increases in subjective nasal blockage throughout the 6 weeks study period in
      either oxymetazoline- or placebo-treated subjects. No significant differences
      were observed between groups for baseline measurements of nasal peak inspiratory
      flow, airway resistance or volume at each clinic visit. A highly significant
      decongestant effect of oxymetazoline was observed at each clinic visit with
      changes in all 3 measurements for both treatment groups, again with no
      significant differences between groups. In summary, in normal subjects, we
      identified no significant nasal blockage or impaired decongestant response to
      oxymetazoline following 4 weeks treatment with oxymetazoline compared to matched
      placebo nasal spray.

PMID- 14579658
TI  - Anterior mandibular positioning device for treatment of snoring and obstructive
      sleep apnoea.
AB  - The aim of this study was to determine the severity of side effects and the
      influence on snoring and the AHI (apnoea-hypopnoea index = number of apnoeas and
      hypopnoeas per hour recording) of an anterior mandibular positioning device (AMP
      device) for treatment of snoring and obstructive sleep apnoea. Questionnaires
      were mailed to a consecutive series of 30 patients who had started treatment with
      an AMP device. The mean follow-up interval from receiving an AMP device to
      answering the questionnaire was 22 months. The perceived degree of sore teeth
      increased statistically significantly (p < 0.01) as a result of the AMP device
      treatment, but there was no increase in the degree of facial pain, salivation, or
      temporomandibular joint pain. The AMP device treatment resulted in a
      statistically significant reduction (p < 0.01) of the mean AHI and of the mean
      percentage of the recording time with loud snoring (p < 0.05). Twenty-two
      patients out of 30 were still using the device at the time of follow-up. In
      conclusion, AMP device treatment was associated with only mild side effects and
      resulted in a statistically significant reduction of the AHI and of the
      percentage of the recording time with loud snoring.

PMID- 14579659
TI  - How to perform adequate nasal packing in posterior epistaxis with difficult
      access.
AB  - Inadequate nasal packing in the treatment of posterior epistaxis can result in an
      increase in patient morbidity and mortality, and also hospital expenditure. The
      presence of a septal spur or septal deviation anterior to the bleeding may
      prevent sufficient local pressure over the bleeding point with a ribbon gauze
      pack. A modified Jobson-Horne probe can be used to ensure a tight ribbon gauze
      application over the bleeding point behind the septal spur or deviation.

PMID- 14579660
TI  - Liposomal amphotericin B treatment for rhinocerebral mucormycosis: how much is
      enough?
AB  - Rhinocerebral Mucormycosis is a potentially life-threatening disease, which
      affects mainly immunocompromised patients. Treatment options include reversing
      immunosuppression, surgery and systemic and local administration of anti-fungal
      medication. Amphotericin B is the primary agent employed, but its use is often
      limited by frequent side effects. Complexing Amphotericin B with lipid structures
      avoids most of the negative side effects, most importantly the dose-limiting
      nephrotoxicity. No consensus has been reached regarding the appropriate duration,
      rate of administration or total dose of treatment. We present a case of a patient
      suffering from Rhinocerebral Mucormycosis treated by extensive surgery and
      Liposomal Amphotericin B. He was treated for 29 days at a rate of 3 mg/kg/d and a
      total dose of 5.6 gram. The dose of Liposomal Aphotericin B used in previously
      published articles ranged from 1.5 mg/kg/d to 5 mg/kg/d. The response to
      treatment may be evaluated by physical examination, microbiological cultures,
      radiological and pathological studies. Taking into account the considerable cost
      of liposomal Amphotericin B and other lipid complexed formulations, it is
      imperative to find out what is the appropriate treatment regime for Rhinocerebral
      and other mucormycosis infections.

PMID- 14579661
TI  - Vision impairment as presenting symptom of a sphenoidal mucocele.
AB  - We present a case of a 27-year-old woman with a sphenoid mucocele, presenting
      with bilateral visual disturbance and pituitary gland dysfunction but without
      nasal or sinus complaints. We would like to emphasize the importance of early
      diagnosis and prompt surgical treatment.

PMID- 14579662
TI  - [Receding adherence to child vaccination programs must be interrupted. Take
      parents' anxiety seriously, establish regional vaccination centers].

PMID- 14579663
TI  - [Measles takes root in Sweden again. Reduced vaccination will result in
      epidemics, about 25 000 cases are expected to occur annually within a 15-year
      period].

PMID- 14579664
TI  - [Parents rely on child vaccinations. But at the same time they distrust the
      medical establishment as shown in a qualitative study of attitudes].

PMID- 14579665
TI  - [Optimal use of markers for cobalamin/folate status. Results from a survey in a
      group of psychogeriatric patients].
AB  - Cobalamin/folate deficiency may lead to neuropsychiatric symptoms. This review
      summarizes present findings concerning the different markers for cobalamin/folate
      deficiency in psychogeriatric patients. These findings suggest the use of plasma
      homocysteine, serum cobalamin and serum folate to evaluate cobalamin/folate
      status in psychogeriatric patients, whereas the use of serum methylmalonic acid
      and whole blood folate could be omitted.

PMID- 14579666
TI  - [Salt and blood pressure--centenarian bone of contention].
AB  - It is first discussed to what extent salt intake/metabolism may have been
      modulated since Homo sapiens' global spread from tropical Africa started some
      200,000 years ago (10-15,000 generations). The effects on blood pressure, volume,
      heart rate etc. have been studied along with nearly 100-fold changes in salt
      intake. Disturbances and risks show up in both extreme ends of this intake range,
      as counterregulatory mechanisms are overswayed, but within a wide (15-20-fold)
      range mean pressure is usually changed only marginally, both in healthy man and
      in rats. When the biological setpoint for intake (salt appetite) has been tested
      in animals it corresponds--when adjusted to man's 65-70 kg bodyweight and
      metabolic rate--in sheep to 8-9 g/day and in rats to some 15 g, and it is
      moderately raised by mental stress. Therefore, human intakes around 10 g daily
      may, after all, reflect our biologically determined setpoint--rather than
      expressing a hedonistic abuse. When at different salt intakes not only blood
      pressure but also heart rate (unfortunately often neglected) are recorded, the
      percentage increase in pressure at high intakes is mostly less than the
      percentage decrease in heart rate--and vice versa at low intakes. Thus, as the
      long-term load on left heart and arteries can be approximated to the product of
      pressure and rate, low intakes often imply increases of long-term load--to which
      comes that the for the left ventricular coronary supply so important diastolic
      phase is shortened. Almost throughout such aspects have been overlooked at the-
      at best--modest reductions of pressure that have been reported at tolerable
      reductions of salt intake. The same is true concerning results showing how
      pressure is reduced considerably more by e.g. three weekly hours of physical
      activity which, in addition, has uniquely beneficial influences on metabolism,
      immune defences, sympatho-hormonal activity, etc. Towards such a background
      suggestions concerning overall reductions of salt intake are hardly justified,
      particularly as the induction of primary (essential) hypertension appears to be
      far more dependent on present-day psychosocial influences by means of central
      enhancements of neuro-endocrine activities.--It is a different matter that salt
      contents in processed foods should be declared, and kept low--first, because
      "salt sensitivity" is not uncommon, second, salt is then easy to add but
      impossible to eliminate.

PMID- 14579667
TI  - [Quicker reporting to the Cancer Registry is required, according to a new
      regulation].

PMID- 14579668
TI  - [Must all health care administrators be identically cloned? You are a chief of
      personnel administration].

PMID- 14579669
TI  - [Constant fear of liability reporting in physicians' everyday work. Impressions
      from interviews with physicians in Western Gotaland].

PMID- 14579670
TI  - [Do not treat interns-researchers unfairly!].

PMID- 14579671
TI  - [700 new physicians in primary health care during two years as a result of the
      list patient system in Norway].

PMID- 14579672
TI  - [Psychosocial issues in bone marrow transplantation: uncertainty and threat to
      life].
AB  - Bone marrow transplantation is a complex medical procedure in which hematopoietic
      stem and progenitor cells are infused into a patient following high-dose
      chemotherapy with or without irradiation. Because the allogeneic transplantation
      is associated with life-threatening physical morbidity, lengthy convalescence,
      and special isolation, the potential for significant psychosocial uncertainty and
      psychological morbidity is high in adult patients. This work provides an overview
      of the medical procedures used in allogeneic transplantation and a review of
      psychosocial and behavioral issues relevant to transplantation. The discussion is
      limited to psychosocial issues pertinent to transplant recipients and donors,
      even though transplantation raises significant psychological issues for medical
      staff, families and caregivers of recipients.

PMID- 14579674
TI  - [Expanding possibilities, strategic considerations, and novel methods in the
      diagnosis and chemotherapy of adult acute myeloid leukemia].
AB  - The WHO classification of adultory acute myeloid leukemia puts the main emphasis
      on prognosis, based mainly upon cytogenetic findings and gene-expression
      profiles. The complex prognostic assessment provides a more solid basis for early
      therapeutic stratification. This review focuses mainly on medical therapy.
      Induction phase is quite uniform, it consists of antracyclin and cytosin
      arabinosid. High-dose cytosin arabinosid is the predominant tool of postinduction
      therapy, especially in the favorable cytogenetic pattern cases. All-trans
      retinoic acid resulted in extremely good results in the promyelocytic cases, and
      this therapy seems to be advantageous in respect of acute DIC, too. Arsenic
      trioxide could be the drug of choice in relapsed promyelocytic leukemia. Some new
      agents are promising in refractory or relapsed cases, i.e. antibodies (Mylotarg)
      or farnesyltransferase inhibitors. The near future may bring about new
      therapeutic approaches, involving immunotherapy (dendritic cell vaccines) or gene
      therapy as well.

PMID- 14579673
TI  - [Theoretical background of angiotensin II receptor blockade and its features in
      clinical pharmacology].
AB  - The angiotensin (II) receptor (1) blockers are known first of all as
      antihypertensive drugs, however, due to the role of the tissue renin-angiotensin
      system (RAS) in different pathological conditions, their clinical importance
      became more pronounced and are at present more widely used. The article gives an
      overview of the recent knowledge in this field. Beside of summarizing
      physiological and the most important pathophysiological aspects of the RAS, as
      well as pharmacokinetic properties of the different angiotensin receptor blocker
      drugs used at present in Hungary, the potential differences in blocking of the
      converting enzyme and the angiotensin II receptors are also reviewed.

PMID- 14579675
TI  - [Blood pressure volatility--a new parameter for determining blood pressure
      variability in type-1 diabetes mellitus].
AB  - INTRODUCTION: In diabetes the heart rate variability is decreased because of the
      autonomic neuropathy and parallel with this phenomenon the overnight blood
      pressure fall is lost. Presumably this change in the hemodynamic parameters is
      connected with the fact that the cardiovascular complications in type 1 diabetic
      patients are 2-4 times more frequent than in healthy patients. The volatility, as
      a new factor, is the dispersion of the proportion of the blood pressure values
      following each other. It exactly reflects the 24-hour blood pressure fluctuation,
      while the dipper/non-dipper determination differentiates only between the daytime
      and night-time average blood pressure values. The volatility follows the changes
      of the measured values in accordance to the frequency of the measurements during
      the whole day. AIM: Our aim was to compare the blood pressure variability of type
      1 diabetic patients (DM) and healthy controls (C). PATIENTS AND METHODS: The
      authors examined 43 diabetic patients from our outpatient clinic and 45 healthy
      people. The blood pressures were measured with Meditech ABPM 02 monitor on
      workdays. The measurements started in the mornings. The frequency of the
      measurements was 20 minutes during the day and 50 minutes at night-time. The
      authors took the history of all the patients and detailed laboratory results. The
      patients also had ophthalmology examination, ECG and echocardiography tests.
      RESULTS: During the Ambulatory Blood Pressure Monitoring we found that the
      systolic volatility of blood pressure values was significantly lower in DM
      compared to C patients. Systolic volatility: 0.133 +/- 0.011 vs. 0.175 +/- 0.014
      p < 0.026. Comparing only the normotonic C and DM group systolic volatility of
      blood pressure values were significantly lower in DM. Systolic volatility: 0.128
      +/- 0.016 vs. 0.177 +/- 0.021 p < 0.036. CONCLUSION: It is an important new
      finding that in type 1 diabetic patient the volatility--a new parameter for
      determining blood pressure variability--is lower than in the healthy control
      group. At normotension state other parameters describing the blood pressure
      variability (like diurnal index or standard deviation) could not show this
      change.

PMID- 14579676
TI  - [Treatment of primary biliary cirrhosis].

PMID- 14579677
TI  - [Commemoration on the 100th birth anniversary of Miklos Jancso, member of the
      Hungarian Academy of Sciences].

PMID- 14579678
TI  - [Hungarian physicians in Vienna].

PMID- 14579680
TI  - Importance of the ratio of omega-6/omega-3 essential fatty acids: evolutionary
      aspects.

PMID- 14579681
TI  - The importance of omega-6/omega-3 fatty acid ratio in cell function. The gene
      transfer of omega-3 fatty acid desaturase.

PMID- 14579682
TI  - Omega-6/omega-3 ratio and brain-related functions.

PMID- 14579683
TI  - Dietary prevention of coronary heart disease: focus on omega-6/omega-3 essential
      fatty acid balance.

PMID- 14579684
TI  - Effects of an Indo-Mediterranean diet on the omega-6/omega-3 ratio in patients at
      high risk of coronary artery disease: the Indian paradox.

PMID- 14579685
TI  - Omega-6/omega-3 fatty acid ratio: the Israeli paradox.

PMID- 14579686
TI  - Linoleic acid to alpha-linolenic acid ratio. From clinical trials to inflammatory
      markers of coronary artery disease.

PMID- 14579687
TI  - The Japan Society for Lipid Nutrition recommends to reduce the intake of linoleic
      acid. A review and critique of the scientific evidence.

PMID- 14579688
TI  - Omega-6/omega-3 polyunsaturated fatty acid ratio and cancer.

PMID- 14579689
TI  - Omega-6/omega-3 fatty acids and arthritis.

PMID- 14579691
TI  - [The establishment of the styles of video-assisted thoracoscopic surgery for
      spontaneous pneumothorax].
AB  - Video-assisted thoracoscopic surgery (VATS) has been widely used in the treatment
      of a pneumothorax, but the high incidence of recurrence from spontaneous
      pneumothorax after VATS is an important problem. In this study, we classified the
      groups into two categories from the thoracoscopic observations, and discussed
      whether or not there was reappearance of pneumothorax. In addition, we examined
      whether adjunctive procedure contributes to recurrent of pneumothorax after
      operation or not. We concluded that there is a tendency to recurrence in the
      group with multiple and skip lesions in the lung, and then concluded that the
      cases apical covering with absorbable material sheet and the use of fibrin glue
      spray was thought to be effective of recurrence of pneumothorax in cases of
      multiple and skip lesions from the intraoperative findings through the
      thoracoscopes. Finally, we examined application of Foley catheter for spontaneous
      pneumothorax under VATS. It is possible that the application of Foley catheter to
      prevention against recurrence of pneumothorax is a valid method.

PMID- 14579690
TI  - [A device to prevent an air-leakage after a thoracoscopic surgery for spontaneous
      pneumothorax].
AB  - PURPOSE: In a thoracoscopic surgery for the patient with spontaneous
      pneumothorax, an air-leakage from the staple-line is one of the most troublesome
      complications. Recently we have been using a polyglycolic acid (PGA) sleeve for
      staple-line reinforcement. The purpose of this study was to investigate an
      efficacy of staple-line reinforcement in the patients who underwent thoracoscopic
      lung resection using an automatic stapler. OBJECTS: Last 4 years, 55 patients
      with primary spontaneous pneumothorax underwent thoracoscopic surgery using an
      automatic stapler. PGA sleeve was used in 19 patients as PGA group, fibrin glue
      was applied to the staple-line in 6 patients as fibrin group and no staple-line
      reinforcement was applied in 30 patients as no-reinforce group. We investigated
      the efficacy of staple-line reinforcement according to the results after surgery
      in these 3 groups. RESULTS: Average drainage time in PGA group, fibrin group and
      no-reinforce group were 2.1, 2.2 and 2.8 days, respectively. In PGA group, the
      drainage time after surgery tended to be short term. The relapse of pneumothorax
      after surgery developed in 2 patients in PGA group (10.5%) and 8 patients in non
      reinforce group (26.7%). In PGA group, the relapse after surgery tended to be low
      rate. CONCLUSIONS: Bioabsorbable PGA sleeve could be an useful device for a
      staple-line reinforcement in the patients who underwent lung resection using
      automatic stapler.

PMID- 14579692
TI  - [A thoracoscopic technique with fibrin glue and polyglycolic acid mesh for the
      injured lung during thoracoscopic operation].
AB  - The injury of the lung occurred during thoracoscopic operation, especially, of
      the fragile, severely emphysematous lung is often difficult to treat. A fibrin
      glue spraying device in which an air compressor was connected to an intravenous
      catheter was constructed, and connected to a Dupuloject syringe. Fibrin glue was
      administered by spraying on the target lesion under a thoracoscopic vision. The
      procedure was done while the tip of the intravenous catheter was held and
      manipulated with forceps through a thoracoport. And then, the polyglycolic acid
      (PGA) mesh that had been cut into small pieces was put on the target lesion with
      forceps. Fibrin glue was sprayed on the lesion again in the above-mentioned
      manner. When necessary, the procedure was repeated. Our technique during
      thoracoscopic operation may be easy to manipulate and be able to apply the target
      lesion uniformly within a short time with a successful repair.

PMID- 14579693
TI  - [Complications of video-assisted thoracoscopic surgery].
AB  - We introduced video-assisted thoracoscopic surgery (VATS) for chest disorders in
      our institution in March, 1992. At first, many of the subjects' disorders were
      non-malignant diseases such as spontaneous pneumothorax, but later we started to
      perform this procedure for lung cancer and mediastinum neoplasm, with improved
      result over thoracoscopic surgical procedures. Now most of the chest disorders at
      our institution are treated with VATS. However, many kinds of complications due
      to manual techniques and instrument troubles surfaced during this period.
      Therefore, in this article we would like to describe the complications that we
      have experienced in our institution using VATS and discuss how we have attempted
      to deal with these complications.

PMID- 14579694
TI  - [Technique for vascular management under thoracoscopic surgery].
AB  - Vascular injury is the most life-threatening complication under thoracoscopic
      surgery. To reduce the risk of vascular injury, knowledge of the anatomy of the
      pulmonary artery, variations in its branching, skillful techniques and careful
      maneuver are necessary. Pulmonary artery being adherent to bronchus is dangerous
      to dissect under thoracoscopy, so it is better to convert to open thoracotomy. A3
      of the left upper lobe is occasionally injured during dissection. It is a safety
      technique for using vascular stapler under thoracoscopic surgery. Stapler leader
      can allow the passage of a stapler to encircle the vessel.

PMID- 14579695
TI  - [Intrathoracic bleeding during video-assisted thoracoscopic lobectomy and
      segmentectomy].
AB  - We have reviewed our experience from January 2001 through January 2003 in 33
      video-assisted thoracoscopic lobectomy and segmentectomy (VATS) in patients with
      cT1N0M0 lung cancer to look at intraoperative bleeding from pulmonary vessels.
      Intraoperative bleeding occurred in 15 cases, 45.5% of 33 VATS procedures, and 2
      cases, 6.1% of VATS procedures converted to an open procedure. Intraoperative
      bleeding occurred more frequently in VATS segmentectomy than VATS lobectomy. Most
      of bleeding from pulmonary arteries and veins can be controlled by compression,
      and they can be controlled thoracoscopically by tie or suture through the utility
      thoracotomy. But, significant bleeding from pulmonary arteries, which can not be
      controlled with a mounted swab, it should be converted to an open procedure.

PMID- 14579696
TI  - [The evaluation of the complications and its management in 800 patients who
      underwent the thoracoscopic surgery].
AB  - Thoracoscopy has been applied to almost all thoracic surgery as shown (table 1).
      Besides an opportunity to follow and encounter a trouble during surgery using
      thoracoscopy, so that it is necessary to become skilled in the prediction and
      management of complication. Nowadays, there are two options on surgery using
      thoracoscopy, thoracoscopic surgery (TS) is performed only on in a port and on a
      mini-thoracotomy with a few ports (video-assisted thoracoscopic surgery: VATS).
      When changing into emergency or converting into open thoracotomy, a muscle
      sparing thoracotomy could be available. The symptoms which occurred in the thorax
      are fundamentally similar during both TS and VATS procedure. However, peculiar
      dangerous factor existed according to the difference in internal organs,
      procedures, and diseases. Critical complications during surgery were as follows,
      i.e., injury of pulmonary vessels and bronchus, tension pneumothorax of the
      opposite lung and tumor implantation of the chest wall. Basically, standard
      practice is the most important to avoid an accident and determine whether
      converting to open thoracotomy should be employed. In the present commentary, we
      would like to present our experiences and propose regarding management.

PMID- 14579697
TI  - [Intraoperative conversion and postoperative complication of video-assisted
      thoracoscopic surgery lobectomy for primary lung cancer].
AB  - By 2002, we had attempted video-assisted thoracoscopic surgery (VATS) lobectomy
      or segmentectomy for 140 primary lung cancer cases. Four cases (2.9%) were
      converted to standard posterolateral thoracotomy for oncologic reasons and aortic
      injury, and 7 cases (5%) were converted to minithoracotomy with a 10 cm incision
      due to almost injuring the vascular system. Average blood loss in these cases was
      379 ml, and there was no blood transfusion required. Seven of these 11 cases had
      true pleural symphysis in the thoracic cavity. The remaining 129 cases, consisted
      of 93 lobectomies and 34 segmentectomies, performed with a minithoracotomy of 5
      cm using 2 ports. Average surgical duration was 227 minutes, and blood loss was
      100 ml. Postoperative complication occurred in 15 patients (11.6%). Major
      complications included 1 broncho-pleural fistula, 1 pulmonary infarction, 1
      cerebral infarction and 1 respiratory failure needed for mechanical ventilation.
      However, there were no hospital deaths. The mean postoperative hospital stay was
      12 days. We recommend that surgeons should pay attention to hilar dissection,
      particularly in the presences of adhesion and carefully judge whether to convert
      to thoracotomy at the time of hemorrhage. The VATS procedure has a low mortality
      and morbidity for lung cancer, but particulaly in high risk patients, requires
      care and management the same as an open thoracotomy.

PMID- 14579698
TI  - [Complications of major lung resections by video-assisted thoracoscopic surgery].
AB  - Lobectomy by video-assisted thoracoscopic surgery (VATS) is gradually being
      performed more frequently because of advantages regarding pain and pulmonary
      function. Complications sometimes occur during or after VATS lobectomy. The
      purpose of this study was to analyze the incidence and the causes of the
      complications. From 1997 to 2003, 185 patients underwent VATS lobectomies.
      Selected diseases for this approach included primary lung cancer (n = 172),
      metastatic lung cancer (n = 7), benign lung tumors (n = 3) and lung sequestration
      (n = 3). The VATS approach was converted to open thoracotomy in 15 (8.1%) of 185
      patients because of bleeding (n = 8), dense hilar adenopathy (DHA, n = 3), local
      extent of disease (n = 3) of intraoperative cardiac trouble (n = 1).
      Intraoperative complications involved injury to a blood vessel (n = 21), stapling
      failure (n = 15), lung injury (n = 7), nerve injury (n = 3), and others.
      Predictive factors for injury to pulmonary arteries was DHA (OR 37.0, p <
      0.0001). Postoperative surgical death occurred in 2 patients due to pneumonia.
      Postoperative morbidity was 22.9%. A surgical operation without any good direct
      or thoracoscopic view or the use of a thoracoscopic tool without knowledge of the
      directions on its use should be avoided. The VATS approach should be replaced by
      open thoracotomy if there are DHA.

PMID- 14579699
TI  - [The prevention and measures to complication of video-assisted thoracoscopic
      surgery for lung cancer patients].
AB  - Video-assisted thoracoscopic surgery (VATS) for patient with lung cancer is
      seemed to be more genetic in future. It is because of small wound, little ache
      and short hospitalization. However, dissection of lymph-nodes is necessary since
      it is lung cancer. Because the thoracoscopic lobectomy is performed in the
      limited space, troubles those we cannot predict can happen. So surgical
      techniques of to prevent troubles are important. And this is the first step to
      avoid postoperative complication. It is necessary that to grasps a state of the
      patient and not to leave perioperative troubles.

PMID- 14579700
TI  - [Intraoperative complications of thoracoscopic surgery for mediastinal tumors].
AB  - We report intraoperative complications of thoracoscopic surgery for mediastinal
      tumors. Forty cases of mediastinal tumor were undergone thoracoscopic surgery at
      the hospital from 1999 to 2002. The patient's ages ranged from 18 to 74 years old
      with a mean of 47.7. Location of these tumors were anteriormediastinal in 20
      cases, middlemediastinal in 6 cases, posteriormediastinal in 11 cases, and
      superiormediastinal in 3 cases. Intraoperative complications were rupture of the
      cyst in 9 cases, bleeding over 150 ml in 5 cases, injury of lung caused by
      adhesiolysis in 5 cases, and injury of nerve in 3 cases. The mean operation time
      was 103.8 minutes. Postoperative hospital stay ranged from 2 to 22 days with a
      mean of 5.9 days. All are alive with no recurrences or postoperative
      complications.

PMID- 14579701
TI  - [Ruptured aortic arch aneurysm with hemorrhagic cardiac tamponade: report of a
      case].
AB  - A 67-year-old female was sent into our hospital for ruptured thoracic aneurysm
      with hemorrhagic cardiac tamponade. Computed tomography (CT) showed pericardial
      effusion and ruptured aortic arch aneurysm. We performed urgent graft replacement
      of the aortic arch using selective cerebral perfusion under mild hypothermia.
      Postoperative course was uneventful.

PMID- 14579702
TI  - [Aortic regurgitation caused by prolapsed noncoronary cusp associated with
      dissecting aortic aneurysm treated by placing a prosthetic graft onto the anulus:
      report of a case].
AB  - A 70-year-old man with severe aortic regurgitation (AR) associated with
      dissecting aortic aneurysm underwent a radical operation. AR was thought to be
      due to dilated sinotubular junction and prolapsed noncoronary cusp caused by
      dissecting flap extended into the sinus of Valsalva. At operation, the
      noncoronary cusp was slightly prolapsed into the left ventricle, but all cusps
      were seemed to be thin and pliable. An isolated "tongue shaped" graft was placed
      onto the anulus of the noncoronary cusp, and a 26 mm Woven Dacron graft was used
      to replace the ascending aorta. Postoperative angiogram showed mild AR and
      improved left ventricular (LV) function. This procedure was effective to repair
      AR caused by prolapsed noncoronary cusp without elongation or thickening of the
      valve.

PMID- 14579703
TI  - [Successful total arch replacement for a 92-year-old woman with acute Stanford A
      aortic dissection: report of a case].
AB  - We reported a successful case of emergent total arch replacement for a
      nonagenarian with acute Stanford A aortic dissection. A 92-year-old woman
      complained of general fatigue, with hypotension. Echocardiography showed moderate
      pericardial effusion and aortic regurgitation. Computed tomography (CT) scan
      showed widely extended aortic dissection from the ascending aorta to descending
      thoracic aorta, and cardiac tamponade. An emergent total arch replacement was
      performed under hypothermic selective cerebral perfusion with bladder temperature
      of 22.5 degrees C. Although she suffered from pneumothorax, renal insufficiency
      and gastrointestinal (GI) bleeding postoperatively, she tolerated the operation
      and complications, well. She is now leading a good life with the same level of
      activities of daily living (ADL) as preoperative one.

PMID- 14579704
TI  - [Adenoid cystic carcinoma of lower lobe of right lung: report of a case].
AB  - A 69-year-old male was admitted to the hospital for further examination of an
      abnormal shadow in the right lower lung fields. He was previously under medical
      treatment for right thoracic empyema. Chest computed tomography (CT) showed a
      solitary mass, 4.5 cm in diameter and broncofiberscopy evidenced a tumor in the
      right lower bronchus. The biopsy was performed and the tumor was diagnosed as a
      pleomorphic adenoma. Intraoperativefinding showed the tumor was 6 cm in gross,
      extended to the left atrium, and a daughter tumor was palpable in the middle
      lobe. The middle and lower lobe were resected. The tumor was located in S9, S10,
      6 x 4 x 3.5 cm in size, 2 daughter tumor was found in the middle lobe, the
      pulmonary vein was thickened by tumor invasion. Pathohistologically, main tumor
      and daughter tumor showed malignant feature, were compatible with adenoid cystic
      cancer. Four years after operation, he is still now alive with home oxygen
      therapy.

PMID- 14579705
TI  - [Intractable pneumothorax for pleuritis carcinomatosis effectively treated with
      bronchial embolization: report of a case].
AB  - A 57-year-old female was admitted with compliant of cough and body weight loss.
      Chest X-ray and thoracic computed tomography (CT) scan revealed a collapsed lung
      and pleural effusion. We diagnosed a pleulitis carcinomatosis. After right chest
      tube drainage was performed, she developed right intractable pneumothorax. It was
      occluded endobronchially by the placement of vascular embolization coils and
      histoacryl. This method is thought to be an effective treatment for intractable
      pneumothorax patients in endstage of lung cancer.

PMID- 14579706
TI  - [DHEA: hormone as antiaging remedies].

PMID- 14579707
TI  - [New aspects of adipocytokines].

PMID- 14579708
TI  - [What is geriatrics?].

PMID- 14579709
TI  - [A request to Japanese geriatrics].

PMID- 14579710
TI  - [Molecular function of Klotho protein].

PMID- 14579711
TI  - [Chronic obstructive pulmonary disease (COPD): problems and the solution in
      elderly patients].

PMID- 14579712
TI  - [Rehabilitation medicine and promotion of quality of life for aged patient].

PMID- 14579713
TI  - [Recent progress in the research of mood disorder].

PMID- 14579714
TI  - [Japanese centenarians].

PMID- 14579715
TI  - [Homebound elderly people in Japan-special reference to intervention study
      including life review method].

PMID- 14579716
TI  - [Development of therapies of Alzheimer's disease].

PMID- 14579717
TI  - [Cerebrovascular diseases in the elderly from gerontological aspects].

PMID- 14579718
TI  - [Diagnosis and therapy for the hypertension in the elderly].

PMID- 14579719
TI  - [Epidemiology of falls among community-dwelling elderly people].
AB  - The purpose of the present study was to report the prevalence and circumstances
      of falls among community-dwelling elderly people in order to contribute to
      prevention of falls in the community. The subjects were 2,774 elderly people who
      participated in health examinations conducted by Tokoname-shi, Aichi Prefecture
      in 2002. The variables investigated in the present study were demography and
      history of falls in the past one-year. Circumstances of falls, e.g. time,
      location, activities associated with falls, cause of falls and degree of injury
      due to falls were asked when the subjects experienced a fall. The prevalence of
      falls among 2,774 subjects was 13.7%. It was significantly higher among women
      (17.2%) than men (8.3%, chi 2 = 48.1, p < 0.001). Prevalence increased as
      subjects get older. Circumstances of falls were assessed in 655 subjects. The
      distribution of time, location, activity associated with falls, cause and injury
      due to falls corresponded with previous fall studies among community dwelling
      elderly people. The incidence of falls was extremely high during the daytime and
      outdoors. Falls occurred most frequently while walking. The majority of falls
      were due to extrinsic factors. About 10% of all falls caused fracture.

PMID- 14579720
TI  - [Factors related to discrepancy in evaluation on functional capacity between
      reports by community-dwelling older people with cognitive decline and their
      family members].
AB  - Overestimation or underestimation of functional capacity in community-dwelling
      older people with cognitive impairment was evaluated between the responses of
      subjects and family members (proxies) by cognitive function level. Out of all the
      residents aged 65 years and over living in Yoita town, Niigata Prefecture in 2000
      (n = 1,673), 1,544 voluntarily participated in the interview survey held at
      community halls or at home (92.3% response). They underwent the Mini-Mental State
      Examination (MMSE) for assessment of cognitive function and answered
      questionnaires comprising socio-demographic, psychological, physical and medical,
      and social activity items (2000/11). According to the age of the subject and MMSE
      score, we defined cognitive decline (MMSE scores < 1 SD below age-specific means,
      n = 371). 158 pairs among 371 subjects with cognitive decline and their proxies
      participated in a follow-up survey (2001/11). The subjects themselves underwent
      MMSE again. 136 subject-proxy pairs reported any complaints of memory-related
      problem and evaluated higher-level functional capacity (TMIG-IC, Tokyo
      Metropolitan Institute of Gerontology Index of Competence). We established
      criteria at follow-up survey as follows: control (n = 29), MMSE scores > 1 SD
      below age-specific means and CDR (Clinical Dementia Rating) = 0: mild cognitive
      decline (MCD) (n = 54), 21 < or = MMSE scores < 1 SD below age-specific means or
      CDR = 0.5); and severe cognitive decline (SCD) (n = 53), MMSE scores 20 < or =
      CDR > 0.5. SCD subjects significantly overestimated total and Instrumental Self
      Maintenance scores in TMIG-IC more than control or SCD subjects. Multiple
      logistic regression analyses indicated that complaints of memory by the proxy,
      response by spouse, and higher levels of education were extracted as
      significantly independent variables affecting overestimation for functional
      capacity. On the other hand, aging affected underestimation.

PMID- 14579721
TI  - [The short version of the Japanese version of the Zarit Caregiver Burden
      Interview (J-ZBI_8): its reliability and validity].
AB  - The Zarit Burden Interview (ZBI) is the instrument most widely used in North
      America and Europe for assessing the burden experienced by family caregivers who
      look after the community-residing impaired elderly. The Japanese version of the
      ZBI (J-ZBI) is the most widely used in Japan for the same purpose. We used data
      from 691 caregivers in relation to their caregiver burden with the 22-item J-ZBI.
      Following a factor analysis, the 8-item short version of the J-ZBI, the J-ZBI_8,
      was proposed with the following two factors: Personal strain (5 items) and Role
      strain (3 items). Cronbach's alpha of the J-ZBI_8 was 0.89, indicating the high
      reliability of this instrument. Pearson's correlation coefficient between J-ZBI
      and J-ZBI_8 was 0.93, and the same coefficient between J-ZBI_8 and item 22 (a
      single global burden) was 0.68. These data indicated that J-ZBI_8 had a high
      concurrent validity. In addition, caregivers who declared that they did not
      encounter any difficulties in looking after the impaired elderly had a
      significantly lower J-ZBI_8 score (3.45; SD = 4.57) than those who claimed that
      they had such difficulties (9.31; SD = 7.19) by the t-test; this indicated that J
      ZBI_8 had a high construct validity. These results indicated that the short
      version, the J-ZBI_8, had a high reliability and validity. Therefore, the J-ZBI_8
      produced results comparable to those of the full version, i.e. the J-ZBI. The
      shorter yet no less reliable and valid 8 item version will thus lead to easier
      administration of the instrument for assessing family caregiver burden in
      clinical settings.

PMID- 14579722
TI  - [Opinions of doctors and nurses about appropriate medical treatment for
      terminally ill geriatric patients].
AB  - We investigated the opinions of medical doctors and nursing staff about desirable
      medical treatment for terminally ill geriatric patients. The purpose of the
      present study is: 1) to examine the recent opinion of doctors and nurses, 2) to
      examine discrepancies of opinions between doctors and nurses on treatment for
      terminal geriatric patients. Doctors and nurses working in long-term care wards
      in four hospitals were enrolled. They were asked to fill in a questionnaire which
      asked about desirable medical treatments for a typical bedridden terminally ill
      geriatric patient. The difference of answers between doctors and nurses were
      analyzed. The most common opinion of the 18 doctors and 84 nurses were as
      follows: 1) for the treatment of relapsing pneumonia, they would perform
      oxygenation, antibiotic injections, and continuous intravenous infusion during
      the period of discontinuation of enteral nutrition, 2) for the treatment of
      relapsing urinary tract infection, they would catheterize patients for a brief
      period and would irrigate the bladder, and would perform antibiotics injection,
      3) for chronic anemia, they would perform iron replacement, 4) for decubitus
      ulcer, they would treat conventionally, and 5) at the final stage just before
      death, they would avoid special therapy for shock after obtaining informed
      consent from patient's family. To most questions, the proportion of each answer
      was almost identical between doctors and nurses; however, there were
      discrepancies concerning "way of nutrition in patients with relapsing pneumonia"
      and "irrigation of the urinary bladder" (p = 0.0544 and 0.0531, respectively). We
      expect that the present study will activate a discussion of what constitutes
      appropriate medical treatment for terminally ill geriatric patients.

PMID- 14579723
TI  - [Dietitians' understanding of personalized nutritional guidance--proposals to
      increase home visits by dietitians].
AB  - Providing elderly people with nutritional care has become important. The aim of
      the present study is to clarify the factors limiting the widespread adoption of
      home visits by dietitians. From September to November 2002, we conducted a
      questionnaire survey of 211 dietitians belonging to the "Houeiken", a group
      devoted to the study of dietician's home visits. We examined the following
      factors: characteristics of the study subjects, result of the home visits,
      factors limiting the widespread adoption of home visits by dietitians, and the
      future of home visits by dietitians. Among the dietitians, 49.7% did nutrition
      management, 30.5% catering management and 12.8% performed home visits (12.8%). In
      total, 53.5% of the dietitians had experience with home visits, having visited an
      average of 1 to 5 people. Typical visits included cooking lessons (27.5%), advice
      on energy intake (25.3%), sharing new recipes (23.6%), and anthropometric
      examinations (13.3%). A total of 76.8% thought their guidance was effective and
      noted significant improvements in terms of caregiver's cooking skills (30.0%),
      patient's understanding of diet (24.0%), and dietary intake (21.5%). The factors
      preventing more widespread home visits by dietitians are: few people are aware
      that this service exists, few people believe that they need this type of
      assistance, it is largely unprofitable, and the number of qualified dieticians is
      insufficient. We believe that more medical staff should become involved in
      dietitian's home visits. Public policies should be implemented to lower
      dietitian's nutritional care fees and increase the education and number of
      dietitians.

PMID- 14579724
TI  - [A case of anaplastic large cell lymphoma associated with Epstein-Barr virus
      infection, representing clinicopathological features of malignant histiocytosis].
AB  - An 82-year-old woman was admitted with fever and anorexia. Aggravated
      pancytopenia and liver dysfunction suggested the presence of disseminated
      intravascular coagulation. The serum ferritin level increased to 9,100 ng/ml.
      Bone marrow aspiration showed an increase of histiocytes with phagocytosis and a
      diagnosis of hemophagocytic syndrome was made. Symptomatic therapy was performed
      because of her deteriorated general condition. She died of multiple organ
      failure, 32 days after admission. Autopsy revealed swollen lymph nodes with
      proliferation of large neoplastic cells containing rich cytoplasm and pleomorphic
      and multi-segmented large nuclei. The immunophenotype of the neoplastic cells was
      LCA-, CD3-, CD5-, CD 20-, CD79a-, UCHL1-, MT1-, CD15-, p80-. Neoplastic cells
      were positive for CD30, mainly in Golgi apparati, and also positive for EBV
      encoded small nonpolyadenylated RNAs (EBER). This case was diagnosed as
      anaplastic large cell lymphoma (ALCL) associated with hemophagocytic syndrome. It
      was estimated that Epstein-Barr virus had played an important role in the
      development of ALCL in the present case.

PMID- 14579725
TI  - [Cytogenetic remission 10 years after the start of monotherapy with interferon
      alpha-2b in elderly chronic myelogenous leukemia].
AB  - A 69-year-old man was found to have leukocytosis and a bleeding tendency, when he
      underwent surgery for hemorrhoids in November 1992, at the age of 69. The patient
      was referred to our department for further examination, and was admitted on
      December 4. On admission, he had hepatomegaly (5 cm) and splenomegaly (12 cm).
      Laboratory data on admission showed that the leukocyte count was
      173,400/microliter, erythrocyte count, 314 x 10(4)/microliter, hemoglobin level,
      10.5 g/dl, hematocrit value, 29.7%, and platelet count, 14.4 x 10(4)/microliter,
      respectively. Peripheral hemogram revealed neutrophilia with a shift to the left
      to promyelocytes, and the positivity of neutrophil alkaline phosphatase (NAP) was
      very low. The bone marrow was hyperplastic with a high M/E ratio (5.8). As the
      chromosome analysis revealed that he had 9:22 translocation in all 20 karyotypes,
      chronic myelogenous leukemia in the chronic phase, was diagnosed. After the daily
      intramuscular administration of 9 megaunits interferon alpha-2b was started on
      December 9, 1992, his leukocyte count stabilized between 5,000 and
      8,000/microliter. Thereafter, intramuscular administration of IFN alpha has been
      continued regularly almost twice a week at the outpatient clinic until now. The
      leukocyte count ranges from 3,000 to 6,000/ml and he is asymptomatic. In April
      1995, complete cytogenetic response was achieved 28 months after the start of
      interferon alpha therapy. The recent bone marrow chromosomes examination showed
      Philadelphia-negative metaphases until now, December, 2002, although major bcr
      abl still remains positive. This case suggests that treatment with interferon
      alpha may still be useful in some elderly patients with chronic myelogenous
      leukemia.

PMID- 14579726
TI  - [Physical and mental health of foreign residents in Japan: a health science and
      nursing perspective].

PMID- 14579727
TI  - Operative results of non-small cell lung cancer clinically presenting mediastinal
      lymph adenopathy.
AB  - OBJECTIVE: Selection of treatment for operable N2 non-small cell lung cancer
      (NSCLC) is still controversial. If considered resectable, we have actively
      performed surgery even for clinical stage IIIA-N2 disease. In this retrospective
      study, surgical results in NSCLC with clinically presenting mediastinal lymph
      adenopathy examined to investigate its indication. METHODS: Consecutive 202
      patients who were preoperatively diagnosed or suspected of mediastinal lymph
      adenopathy and underwent operation were investigated for such as pathological
      judgement of nodal metastasis, completeness of operation and prognosis.
      Perioperative chemotherapy and/or radiotherapy was performed in 56 patients.
      RESULTS: Pathological diagnosis of nodal status was N0 in 64 patients, N1 in 27,
      N2 in 104 and N3 in 7. Complete resection was performed in 109 patients (54%). In
      111 patients with pathologically proven N2 (pN2), only 40 (36%) were completely
      resected. The reason of incomplete resection included extranodal extension of
      mediastinal nodal metastasis in 31 patients, pleural dissemination in 18,
      extension of primary tumor to mediastinum in 11. Median post-operative survival
      time was 553 days, and survival rates at 2- and 5-years were 43% and 22%,
      respectively. In all pN2, survival rates at 2- and 5-years were 33% and 11%,
      respectively. In 40 patients of completely resected pN2, survival rates at 2- and
      5-years were 42% and 22%, respectively, whereas those were 17% and 5% in 64
      patients with incompletely resected pN2. The positive effect of perioperative
      treatment on survival was not apparent. CONCLUSIONS: If resectable, surgical
      approach to N2 might be approved, however, extensive examination is required
      prior to therapy to avoid incomplete resection.

PMID- 14579728
TI  - High-throughput isolation of recombinant antibodies against recombinant
      allergens.

PMID- 14579729
TI  - Primers for EPIC amplification of intron sequences for fish and other vertebrate
      population genetic studies.

PMID- 14579730
TI  - Expression of active RNA-activated protein kinase (PKR) in bacteria.

PMID- 14579732
TI  - Counter-selection facilitated plasmid construction by homologous recombination in
      Saccharomyces cerevisiae.

PMID- 14579731
TI  - Glass slide-based agarose gel electrophoresis for determining the efficiency of
      RNA amplification and cyanine dye incorporation during RNA labeling.

PMID- 14579734
TI  - Complex DNA melting profiles of small PCR products revealed using SYBR Green I.

PMID- 14579733
TI  - A/T-rich inverted DNA repeats are destabilized by chaotrope-containing buffer
      during purification using silica gel membrane technology.

PMID- 14579735
TI  - Open-dish incubator for live cell imaging with an inverted microscope.
AB  - Here we describe the design and fabrication of an inexpensive cell culture
      incubator for the stage of an inverted light microscope for use in live cell
      imaging. This device maintains the temperature of the cell culture at 37 degrees
      C with great stability and, after reaching equilibrium, provides focal stability
      of an image for 20-25 min with oil-immersion lenses. We describe two versions of
      the incubator: one for use with standard 60-mm plastic culture dishes, and the
      other version for imaging of cells on glass coverslips. Either can be made for
      less than $400. Most components are widely available commercially, and it
      requires only simple wiring and 3 h to assemble. Although the device is generally
      useful for live cell imaging on an inverted microscope, it is particularly
      suitable for work in which instruments are introduced into the culture, such as
      electrophysiology or micromanipulation. The design is based on the principle that
      control performance is limited by the lag time between detection and response.
      The key element of the design is a heated, temperature-controlled aluminum ring
      serving as a mini-incubator surrounding the culture vessel. For this reason, we
      call our design a "ringcubator."

PMID- 14579736
TI  - Body window-enabled in vivo multicolor imaging of transplanted mouse islets
      expressing an insulin-Timer fusion protein.
AB  - Type 1 diabetes results from the selective destruction of insulin-producing beta
      cells in the islets of Langerhans, and autoimmune T cells are thought to be the
      mediators of this destruction. T cells are also responsible for allorejection
      once the islets are transplanted into a patient to reduce the negative
      consequences of a lack of insulin. To better understand these processes, we have
      developed a transgenic mouse expressing proinsulin II tagged with a live-cell
      fluorescent reporter protein, Timer. Timer protein is unique because it changes
      color from green to red in the first 24 h after synthesis. With this marker,
      insulin synthesis can be carefully monitored through fluorescent changes over
      time. To complement this new biotechnological research tool, we designed a body
      window to allow for in vivo imaging over time of the islets transplanted under
      the kidney capsule. The window device, which is sutured to replace the underlying
      skin and body wall over the site of islet transplantation, may be used to
      simultaneously observe beta cells and T cells that have been labeled with a
      fluorochrome distinguishable from Timer. The imaging of both insulin-producing
      cells and T cells may be carried out repeatedly for a week or more with no need
      for repeated surgery, while preserving the life of the studied animal.

PMID- 14579737
TI  - Removal of endotoxin by reverse phase HPLC abolishes anti-endothelial cell
      activity of bacterially expressed plasminogen kringle 5.
AB  - The success of recombinant protein expression/purification in Escherichia coli
      depends on a high-fidelity system rendering purified proteins free of confounding
      contaminants such as endotoxin. Here we report on the expression and purification
      of a cryptic plasminogen-derived domain, kringle 5, which was previously reported
      to specifically inhibit endothelial cell growth and, therefore, angiogenesis.
      Using a histidine (HIS)-tag expression and Ni(+)-NTA agarose purification system
      identical to previous reports, we found that our purified recombinant kringle 5
      did inhibit endothelial cell growth, but this activity could not be eradicated by
      heat denaturing or proteolysis of kringle 5 with various proteases. This led us
      to suspect the presence of a contaminant in the purified samples. Quantitative
      endotoxin testing using a limulus amoebocyte lysate assay revealed that all
      samples purified by Ni(+)-NTA agarose alone harbored high concentrations of
      endotoxin that could not be removed by additional purification on anion exchange
      chromatography. Finally, when kringle 5 was rendered endotoxin-free by
      purification on reverse phase high-performance liquid chromatography (HPLC),
      there was a complete loss of endothelial cell growth inhibitory activity. These
      results strongly suggest that endotoxin-free recombinant kringle 5 may not
      possess anti-angiogenic activity and demonstrates that, especially in
      angiogenesis type assays, endotoxin contamination can lead to a misinterpretation
      of results.

PMID- 14579738
TI  - Transformation of yeast using calcium alginate microbeads with surface
      immobilized chromosomal DNA.
AB  - Yeast artificial chromosomes (YACs) are useful cloning vectors that have the
      capacity to carry large DNA inserts. The largest barrier to using such large DNA
      molecules in transformation experiments has been their physical instability in
      solution. We developed a new method of transforming yeast using chromosome-sized
      DNA. The method uses calcium alginate microbeads to immobilize high-density yeast
      chromosomal DNA. Chromosomal DNA immobilized on microbeads is physically
      stabilized compared with naked chromosomal DNA. The microbead-mediated
      transformation performed well, not only with respect to the transformation
      frequency with large DNA molecules (> 100 kb) but also in successful
      transformation using split chromosome DNA that exceeded 450 kb.

PMID- 14579739
TI  - Selection of candidate housekeeping controls in tomato plants using EST data.
AB  - Because the expression levels of housekeeping genes are relatively constant in
      most tissues, they are often useful controls when quantifying gene expression. We
      present an analytical method for identifying candidate housekeeping controls
      using expressed sequence tags (ESTs) from The Institute for Genomic Research
      Tomato Gene Index. We found relative expression levels for a collection of 127
      transcripts and calculated the percentage of cDNA libraries that had expression
      levels (for a given transcript) within 2-fold through 10-fold ranges. When all
      libraries were considered together, the highest ranked housekeeping controls
      included transcripts for a DanJ-like protein, translationally controlled tumor
      protein, two alpha-tubulins, cyclophilin, and glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH). For each organ (leaf, root, fruit, and flower), at least
      one transcript was found that occurred within a 2-fold range of expression in all
      respective libraries. These included transcripts for alpha-tubulin, DnaJ-like
      proteins, phosphoglycerate kinase, and GAPDH, although different transcripts
      appear better suited than others for different tissues. This analytical method is
      useful for identifying candidate housekeeping controls in particular tissues and
      at particular levels of expression and would be relevant for any species for
      which significant EST data exist.

PMID- 14579740
TI  - Generation of a phagemid mouse recombinant antibody fragment library by multisite
      directed mutagenesis.
AB  - A nonimmune phagemid recombinant antibody fragment (rFab) library was generated
      with a nominal diversity of 1.16 x 10(7) using the QuikChange Multi Site-Directed
      Mutagenesis kit. Two degenerate primers spanning the third complementarity
      determining region (CDR) loops of the antibody fragment light and heavy chain
      were mutated such that eight or nine amino acids were randomly changed per CDR
      loop. Seven proteins were used to evaluate the library quality. Protein-specific
      rFab antibodies were selected after three panning cycles. From 12% to 64% of the
      randomly selected colonies produced positive ELISA signals to the phagemid rFabs.
      Multisite-directed mutagenesis allowed a diverse rFab library to be rapidly
      constructed while retaining the structural framework of a Fab that had been
      optimized for production in Escherichia coli.

PMID- 14579741
TI  - Random priming PCR strategy to amplify and clone trace amounts of DNA.
AB  - Here we report a new methodology to study trace amounts of DNA of unknown
      sequence using a two-step PCR strategy to amplify and clone target DNA. The first
      PCR is carried out with a partial random primer comprised of a specific 21
      nucleotide 5' sequence, a random heptamer, and a 3' TGGC clamp. The second PCR is
      carried out with a single 19-nucleotide primer that matches the specific 5'
      sequence of the partial random primer. Using human and Mycoplasma genitalium DNA
      as examples, we demonstrated the efficiency of this approach by effectively
      cloning target DNA fragments from 1 pg DNA sample. The cloning sensitivity could
      reach 100 fg target DNA templates. Compared to the strategy of first adding
      adapter sequences to facilitate the PCR amplification of unknown sequences, this
      approach has the advantage of allowing for the amplification of DNA samples in
      both natural and denatured forms, which provides greater flexibility in sample
      preparation. This is an efficient strategy to retrieve sequences from trace DNA
      samples from various sources.

PMID- 14579742
TI  - Rapid assay to detect possible natural substrates of proteases in living cells.
AB  - Proteolysis is a regulatory step in many physiological processes, but which
      proteases in what cellular sites are involved in activation or degradation of
      which peptides is not well known. We developed a rapid assay consisting of living
      cells and fluorogenic protease substrates to determine which bioactive peptides
      are possible natural substrates of a specific protease with the multifunctional
      or moonlighting protein CD26/dipeptidyl peptidase IV (DPPIV) as a model.
      CD26/DPPIV catalyzes cleavage of peptides from the amino terminus of peptides
      with proline at the penultimate position. Many biologically active peptides, such
      as beta-casomorphin1-5, contain proline in the penultimate position. We incubated
      living Jurkat cells, which are T cells that lack CD26/DPPIV, and CD26/DPPIV
      transfected Jurkat cells in the presence of the fluorogenic substrate [Ala-Pro]2
      cresyl violet (Magic Red) and beta-casomorphin1-5. Fluorescent cresyl violet was
      generated by CD26/DPPIV-transfected Jurkat cells but not by wild-type Jurkat
      cells with a Km of 3.7 microM. beta-Casomorphin1-5 appeared to be a possible
      natural substrate of CD26/DPPIV, because it inhibited production of fluorescence
      competitively (Ki = 60 microM). The assay using living cells and a fluorogenic
      protease substrate is an efficient system to determine whether specific peptides
      are possible natural substrates of a particular protease.

PMID- 14579743
TI  - Direct retransformation of yeast with plasmid DNA isolated from single yeast
      colonies using rolling circle amplification.
AB  - We have efficiently amplified plasmid DNA from single yeast colonies using
      rolling circle amplification (RCA). The amplified DNA can be directly used for
      restriction digestion, DNA sequencing, or yeast transformation. The RCA-based
      high-fidelity amplification would be useful for plasmid manipulation in a variety
      of yeast-based systems, particularly for high-throughput analyses.

PMID- 14579744
TI  - Identifying Mycobacterium species and strain typing using a microfluidic labchip
      instrument.
AB  - We developed schemes for rapid identification of Mycobacterium species and strain
      typing using a microfluidic labchip instrument. A 439-bp region of the gene that
      codes for the 65-kDa heat shock protein (hsp65), which has sequence polymorphisms
      specific for most mycobacterial species, was examined using PCR-restriction
      analysis (PRA). We performed PRA in duplicate, using 2 strains each of 12
      species, and observed that fragment sizes (bp) determined automatically by the
      instrument were consistently smaller than the correct sizes for each of the
      species as determined by sequence analysis (mean variance, < 7 bp). Mycobacterium
      tuberculosis isolates were typed with the labchip instrument using mycobacterial
      interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) typing,
      which determines the number of copies of repeated units at 12 loci in the genome
      based on product size after PCR amplification. Seven strains with one to six
      repeat copies at each locus were examined. Sizes were smaller by a mean of 13.47
      bp compared with correct sizes predicted by sequence analysis, but could be used
      to correctly identify all strains types. Isolates of Mycobacterium chelonae and
      Mycobacterium abscessus were typed using randomly amplified polymorphic DNA
      (RAPD) electrophoresis, and patterns obtained using the labchip instrument were
      compared with multilocus enzyme electrophoresis (MEE) types. Patterns were
      distinct and reproducible for all strains except those with closely related MEE
      types. The labchip instrument is a versatile alternative for sizing mycobacterial
      DNA fragments.

PMID- 14579745
TI  - Parameters influencing high-efficiency transfection of bacterial artificial
      chromosomes into cultured mammalian cells.
AB  - Although bacterial artificial chromosomes (BACs) provide a well-characterized
      resource for the analysis of large chromosomal domains, low transfection rates
      have proven a significant limitation for their use in cell culture models. Using
      TP53 BAC clones that contain expression cassettes for enhanced green fluorescent
      protein or red fluorescent protein, we have examined conditions that promote BAC
      transfection in hamster, human, and mouse cell lines. Atomic force microscopy
      shows that BAC transfection efficiency correlates with the generation of small,
      highly condensed but dispersed lipid: BAC DNA transfection complexes. BAC DNA
      purity and concentration are critical for good transfection; debris from
      purification columns induces the formation of large aggregates that do not gain
      entry into the cell, and DNA concentrations must be optimized to promote
      intramolecular condensation rather than intermolecular linking, which also causes
      aggregation and diminished transfection efficiency. The expression of both
      markers and genes within BACs initially occurs at lower levels than observed with
      plasmids, requiring 3-5 days to evaluate the transfection results. We also show
      that BACs can be co-transfected with other BACs, which provides for increased
      experimental flexibility.

PMID- 14579746
TI  - An easy setup for double slide microarray hybridization.

PMID- 14579747
TI  - Mycoplasma infection significantly alters microarray gene expression profiles.

PMID- 14579748
TI  - Evaluation of a microarray for genotyping polymorphisms related to xenobiotic
      metabolism and DNA repair.
AB  - We present an oligonucleotide microarray ("MetaboChip") based on the arrayed
      primer extension (APEX) technique, allowing genotyping of single nucleotide
      polymorphisms (SNPs) in genes of interest for cancer susceptibility and
      pharmacogenetics. APEX consists of a sequencing reaction primed by an
      oligonucleotide anchored with its 5' end to a glass slide and terminating one
      nucleotide before the polymorphic site. The extension with one fluorescently
      labeled dideoxynucleotide complementary to the template reveals the polymorphism.
      Ninety-three SNPs in 42 genes were selected among those resequenced in the
      context of the SNP500 project, using a set of 102 reference DNA samples from the
      Coriell Biorepository. Selected SNPs belong to the following genes: ADH1B, ALDH2,
      APEX, CDKN2A, COMT, CYP1A1, CYP1A2, CYP1B1, CYP2A6, CYP2C19, CYP2C9, CYP2E1,
      CYP3A4, DRD2, DRD4, EPHX1, ERCC1, ERCC2, ERCC4, ERCC5, GRPR, GSTA4, GSTM3, GSTP1,
      GSTT2, LIG3, MDM2, MGMT, MPO, NAT1, NAT2, NQO1, OGG1, PCNA, POLB, SLC6A3, SOD2,
      TP53, XRCC1, XRCC2, XRCC3, and XRCC9. We assessed the performance of APEX by
      comparing the results obtained with MetaboChip against those reported by the
      SNP500. Among 88 SNPs that yielded signals, 6 showed less than 99% of
      concordance, whereas 82 performed accurately, showing that APEX is a reliable and
      sensitive genotyping method.

PMID- 14579749
TI  - Optimizing stringency for expression microarrays.
AB  - While several studies have reported methods to optimize expression microarray
      protocols, none have dealt directly with hybridization wash stringency. We
      designed a series of experiments to determine the optimal stringency conditions
      for microarray experiments, using reproducibility and magnitudes of log2
      (test/reference) ratio values as measures of quality. Low-stringency wash
      conditions of cell line hybridizations led to nonspecific binding, resulting in
      increased intensities, decreased magnitude of ratios, and poor reproducibility.
      Relatively high-stringency wash conditions were found to give the best
      reproducibility and large magnitude ratio changes, although increasing the
      stringency beyond this point led to lower magnitude ratios and poorer
      reproducibility. The expression levels of the ERBB2 oncogene in the BT474 versus
      MCF7 cell lines showed that high-stringency wash conditions gave the best
      agreement with real-time quantitative PCR, although the magnitude of the changes
      by microarray was smaller than for real-time quantitative PCR. Analysis of a
      series of cell lines washed at the optimized stringency indicated that the rank
      order of relative expression levels for ERBB2 microarray clones agreed well with
      the rank order of ERBB2 levels, as measured by quantitative PCR. These results
      indicate that the optimization of stringency conditions will improve microarray
      reproducibility and give more representative expression values.

PMID- 14579750
TI  - Rapid diagnostic assays in the genomic biology era: detection and identification
      of infectious disease and biological weapon agents.
AB  - In this special section of BioTechniques, we examine the role of rapid molecular
      technologies in the detection and identification of agents of infectious disease
      (ID) and biological weapons (BWs). Besides the threat posed by the global
      proliferation of BW technologies, there are numerous emerging and reemerging ID
      agents with significant public health consequences. Further compounding this
      already complicated situation are the estimated 600 million international
      tourists annually, many with the potential to the spread disease globally in a
      matter of hours. While clinical laboratories have key roles in the detection and
      identification of potential ID/BW agents, most staff are unfamiliar with these
      agents because of their rarity and the often laborious conventional methodologies
      needed to identify them. To meet this challenge, a vast array of rapid assay
      strategies has been developed for use in clinical diagnostics and environmental
      detection. Technologies have been developed or adapted to the challenges posed by
      these agents, permitting detection and identification in several minutes to
      hours. In particular, the development of improved reagents and detection systems
      has led to dramatic improvements in the sensitivity and specificity of
      immunological and nucleic acid-based systems, allowing an ever-increasing range
      of analytes to be identified and quantitated. In the accompanying articles, we
      have brought together experts from the many overlapping aspects of this arena in
      order to present a comprehensive and critical analysis of these technologies.

PMID- 14579751
TI  - Immunoassay of infectious agents.
AB  - Immunoassays have evolved for a broad range of applications since the pioneering
      work of Yalow and Berson who developed the first competitive radioimmunoassay
      (RIA) for human insulin in 1959. Immunoassay detection of specific antigens and
      host-produced antibodies directed against such antigens consitutes one of the
      most widely used and successful methods for diagnosing infectious diseases (IDs).
      The number and variety of new assay systems that are continually being developed
      reflect the increasing demand for immunoassays possessing greater sensitivity,
      speed, and ease of use. This trend has been driven, in part, by the need for
      improved immunodiagnostic systems to perform rapid testing and counter emerging
      IDs and biothreat (BT) agents. Another factor driving this trend is the need to
      integrate immunoassays with more sensitive nucleic acid-based methods for a
      comprehensive approach. Here we examine the development of immunoassays, some of
      the key formats used for the detection and identification of BT/ID agents, and
      the application of these technologies under different scenarios.

PMID- 14579752
TI  - Nucleic acid approaches for detection and identification of biological warfare
      and infectious disease agents.
AB  - Biological warfare agents are the most problematic of the weapons of mass
      destruction and terror. Both civilian and military sources predict that over the
      next decade the threat from proliferation of these agents will increase
      significantly. In this review we summarize the state of the art in detection and
      identification of biological threat agents based on PCR technology with emphasis
      on the new technology of microarrays. The advantages and limitations of real-time
      PCR technology and a review of the literature as it applies to pathogen and virus
      detection are presented. The paper covers a number of issues related to the
      challenges facing biological threat agent detection technologies and identifies
      critical components that must be overcome for the emergence of reliable PCR-based
      DNA technologies as bioterrorism countermeasures and for environmental
      applications. The review evaluates various system components developed for an
      integrated DNA microchip and the potential applications of the next generation of
      fully automated DNA analyzers with integrated sample preparation and biosensing
      elements. The article also reviews promising devices and technologies that are
      near to being, or have been, commercialized.

PMID- 14579753
TI  - [Treatments for liver metastases based on the original tumor].

PMID- 14579754
TI  - [Image evaluation of liver metastases].
AB  - In imaging diagnosis of metastatic liver neoplasms, particularly in preoperative
      evaluation, it is necessary to detect all lesions, note involved hepatic
      segments, determine relations with intrahepatic vascular structure, evaluate
      local invasiveness of lesions, and exclude the presence of extrahepatic
      metastases. Various imaging features can be demonstrated with appropriate imaging
      techniques and provide useful information for differential diagnosis or
      determination of the primary site. Multip lemodalities such as ultrasonography,
      computed tomography (CT), magnetic resonance imaging (MRI), and angiography
      including CT during arterial portography and CT during hepatic arteriography are
      used for the diagnosis of metastatic liver neoplasms, and it is important to know
      the characteristics of each. Among the advances in imaging technology, the
      practical use of super-paramagnetic iron oxide-enhanced MRI (SPIO-enhanced MRI)
      has had a major impact. SPIO-enhanced MRI is a promising imaging modality for the
      detection of metastatic liver neoplasms because of its relatively high
      sensitivity and extremely high specificity. Accumulation of additional results is
      still necessary, but the imaging strategy for metastatic liver neoplasms will
      likely be based mainly on SPIO-enhanced MRI in the future.

PMID- 14579755
TI  - [Treatment strategy for hepatic metastases of colorectal cancer].
AB  - Over the past 25 years, 125 patients with colorectal liver metastases underwent
      167 hepatectomies in our department. The 1-, 3-, and 5-year survival rates after
      the initial hepatectomy were 90%, 58%, and 51%, respectively, and those after
      repeated hepatectomy were 88%, 60%, and 42%, respectively. The predictive factors
      significantly associated with poor prognosis after initial hepatectomy were
      maximal diameter of metastasis (> or = 5 cm), distribution pattern in the liver
      (multiple bilobar), number of nodules (> or = four), and presence of extrahepatic
      metastases. A disease-free interval of > 6 months after initial hepatectomy was a
      significant factor for prolongation of survival after repeat hepatectomy.
      Patients with hilar node metastases at the initial hepatectomy did not receive a
      survival benefit from hepatectomy, while 5 patients underwent repeat hepatectomy
      with lymphadenectomy for remnant liver and hilar node metastases with a disease
      free interval of > 8 months and 4 of them survived for > 5 years. Our treatment
      strategies for colorectal hepatic metastases are as follows: 1) hepatectomy is
      the first choice for < 4 liver metastases without extrahepatic disease; 2) a
      careful evaluation for liver resection is performed for patients with > or = 4
      liver metastases receiving hepatic arterial infusion chemotherapy because of the
      high frequency of hepatic and/or extrahepatic recurrence after initial
      hepatectomy; 3) the presence of hilar node metastases at the initial hepatectomy
      should be excluded from surgical indications; 4) simultaneous single metastasis
      limited to the lung is an indication for lung resection; and 5) a suitable
      indication for repeat hepatectomy for hepatic recurrence is patients with a
      longer disease-free interval. Aggressive surgery based on the optimum patient
      selection can contribute to clinical benefit, including long-term survival in
      patients with colorectal liver metastases.

PMID- 14579756
TI  - [Treatment strategy for liver metastasis from breast cancer].
AB  - Distant metastases, including supraclavicular and parasternal lymph node
      metastases, were observed in about 23% of primary breast cancers in our
      institute. The liver was the primary site of metastasis in about 8% of cases.
      This rate was low compared with metastases to the bone, lung, and pleura. As
      treatment for metastatic lesions to other organs fails, metastatic frequency to
      the liver increases. As treatment, whole-body control with chemoendocrine therapy
      is fundamental. In chemotherapy, anthracyclines are the first choice and taxanes
      are the second, but the use of herceptin for herceptest-positive patients should
      be considered. Endocrine therapy should be adopted for patients with hormone
      receptor-positive tumors. Achieving a temporary partial response is possible,
      although cure is almost impossible. The prognosis of patients with metastasis to
      the liver is poor; the 3- and 5-year survival rates are 22% and 11%,
      respectively. We must emphasize the prevention of liver metastases by early
      detection using mass screening with mammography and neoadjuvant/adjuvant
      chemoendocrine therapy.

PMID- 14579757
TI  - [Management of patients with hepatic metastases from gastric carcinoma].
AB  - Many studies have reported the benefit of hepatic resection for metastatic tumors
      from colorectal cancer. However, the significance of hepatic resection for
      gastric metastasis has been controversial. Peritoneal metastases were recognized
      in 40% of gastric cancer patients with liver metastases, and metastatic lesions
      in both lobes of the liver were seen in 60% of patients. Resection with
      curability B was performed in only 10% of the all gastric cancer patients with
      liver metastases. However, the overall 5-year survival rate of curability B
      resection was more than 30%, suggesting that it is worth while treating
      metastases of gastric cancer to the liver. Both synchronous and metachronous
      metastases are indications for hepatectomy. If there is only one liver
      metastasis, with no peritoneal and paraaortic lymph node metastases, curability B
      resection can be performed. Although there is no consensus on the method of
      hepatectomy, wedge resection is satisfactory. As systemic chemotherapy, S-1 +
      cisplatin results in a response rate of 50% in patients with metastases to the
      liver. As arterial infusion chemotherapy, the 5-fluorouracil-doxorubicin
      mitomycin (FAM) regimen yields a response rate of more than 70% including 15%
      complete response rate. FAM is thus a superior regimen, but care must be taken to
      prevent complications resulting from intraarterial infusion of outside the vas
      due to deviation of the catheter.

PMID- 14579758
TI  - [The treatments of hepatic metastasis from pancreato-biliary cancer].
AB  - Hepatic metastases of pancreatobiliary cancer have a dismal patient prognosis of
      approximately 1 year after diagnosis. There have been a few reports in the
      literature on aggressive treatment of these patients with the intention of cure.
      For hepatic metastases from biliary cancer, hepatic resection has been performed
      in a small number of patients, resulting in a median survival time of less than
      12 months. In our series of 7 patients, median survival time was 9 months. For
      hepatic metastases of gallbladder carcinoma, long-term (> 3-year) survivors have
      been reported. In our series of 16 patients, median survival time was 8 months,
      but one patient is still alive after more than 5 years. For simultaneous hepatic
      metastases of pancreas cancer. Howard et al and Takada et al have reported the
      results of aggressive surgical resection in 10 and 11 consecutive patients,
      respectively. The median survival times in their series were 11 and 6 months
      after hepatic resection and pancreaticoduodenectomy, respectively. These results
      cannot justify aggressive resection for patients with hepatic metastases of
      pancreatic cancer. In most series previously reported, the treatment for hepatic
      metastases from pancreatobiliary malignancies was systemic and regional
      chemotherapy, especially hepatic arterial infusion chemotherapy. However, there
      is no evidence suggesting a beneficial effect of cancer chemotherapy on
      prognosis. Therefore new therapeutic modalities should be developed to improve
      the outcome of the treatment of hepatic metastases of pancreatobiliary cancer.

PMID- 14579759
TI  - [Surgical treatment of colorectal liver metastasis].
AB  - The aim of this study was to evaluate retrospectively the long-term results of
      our approach, which consists of surgically treating every case in which radical
      resection of all metastatic disease was technically feasible. The indications for
      surgical resection for liver metastases from colorectal cancer remain
      controversial. Several clinical risk factors have been reported to influence
      survival. Between 1980 and 2001, 304 patients underwent curative hepatic
      resection for metastatic colorectal cancer at our institution. Survival rates and
      disease-free survival as a function of clinical and pathological determinants
      were examined retrospectively. The overall 3-, 5, 10-, and 20-year survival rates
      were 51%, 36%, 26%, and 25%, respectively. The stage of the primary tumor, lymph
      node metastasis, multiple nodules, a high preoperative CEA level and a short
      interval between treatment of the primary and metastatic tumors were
      significantly associated with a poor prognosis. Patients with 4 or more
      metastases had almost the same survival rate as those with 2 or 3 nodules.
      Extrahepatic metastases or invasion at hepatectomy did not worsen the survival
      rate if curatively resected. These results confirm that surgical resection is
      useful for treating liver metastases from colorectal cancer. While multiple
      metastases significantly impair patient prognosis, the life expectancy of
      patients with 4 or more nodules makes their resection mandatory.

PMID- 14579760
TI  - [Treatment of metastatic liver carcinoma: chemotherapy and immunotherapy].
AB  - The treatment regimens that are considered to be effective against metastatic
      colorectal carcinoma and available in Japan are levofolinate calcium (Isovorin)/5
      fluorouracil (5-FU), irinotecan hydrochloride (Topotecin, CPT-11), and repeated
      low-dose cisplatin/5-FU. In the USA and Europe, many randomized clinical trials
      of regimens combining CPT-11 or oxaliplatin (Oxa) with folinate calcium
      (Leucovorin, LV)/5-FU have been conducted. However, in Japan these three regimens
      are used sequentially based on the performance status of each patient, and the
      use of Oxa has not been approved. LV/UFT, and TS-1 will likely be approved soon
      for colorectal carcinoma. These two regimens may advance the strategy of
      chemotherapy for colorectal carcinoma. There is no report showing an obvious
      clinical effect of nonspecific immuno therapy against metastatic colorectal
      carcinoma. On the other hand, it has been clarified that monoclonal antibodies to
      the molecular targets such as vascular endothelial growth factor (VEGF) and
      epidermal growth factor receptor (EGFR) show a clear clinical effect when they
      are used together with chemotherapy. It is important to accumulate further
      evidence clarifying the best chemotherapy for metastatic colorectal carcinoma.
      Furthermore, it is important that effective molecular-targeting drugs, including
      the monoclonal antibody to VEGF bevacizumab, become available in Japan soon.

PMID- 14579761
TI  - [The public system for dealing with incidental accidental report in Tokyo
      Metropolitan Government].
AB  - How to prevent medical adverse events and augment the public's confidence in
      healthcare has become an urgent one of the highest-priority medical policy issues
      in Japan. Accident reports for administrative organs are very usefully for
      patient safety, but are not concerned with the legal duty required under the
      Medical Act Law. Extending previous work, we established the public system
      following. First, we gave notice all hospital in Tokyo Metropolitan how
      incidental range should be reported. Second, we established "neutral center for
      collect incidental reports". Third, we established "Tokyo Metropolitan Patients'
      Advisory Service" that collects patient's complaints. We convince that
      cooperative actions with administrative organ, hospital and patients are very
      usefully for patient safety and should be extending in Japan.

PMID- 14579762
TI  - [What we can learn from a case of medical malpractice].

PMID- 14579763
TI  - Requirements on core performance measures are set to increase.

PMID- 14579764
TI  - Recent power outage puts spotlight on problem areas.

PMID- 14579766
TI  - Discharge planning advisor. Independent CMs face greater HIPAA challenge.

PMID- 14579765
TI  - Tips from a recent JCAHO survey.

PMID- 14579767
TI  - New quality trend puts spotlight on success.

PMID- 14579768
TI  - Are nursing home residents safe?

PMID- 14579769
TI  - Patient safety alert. Hospital safety initiative targets behavioral health unit.

PMID- 14579770
TI  - Patient safety alert. Study shows safety risks for children, value of tool.

PMID- 14579771
TI  - Selectin ligands on T cells.

PMID- 14579772
TI  - Skin homing T cells.

PMID- 14579773
TI  - Cutaneous lymphocyte localization in the pathogenesis of psoriasis.

PMID- 14579774
TI  - The role of fucosylation in leukocyte adhesion deficiency II.

PMID- 14579775
TI  - Substrate specificity and synthetic use of glycosyltransferases.

PMID- 14579776
TI  - Control of FucT-VII expression in CD4+ T cells.

PMID- 14579777
TI  - Selectin avidity modulation by chemokines at subsecond endothelial contacts: a
      novel regulatory level of leukocyte trafficking.

PMID- 14579778
TI  - Interactions of selectins with PSGL-1 and other ligands.

PMID- 14579779
TI  - Saturation transfer difference NMR spectroscopy for identifying ligand epitopes
      and binding specificities.

PMID- 14579780
TI  - Chemokine receptor antagonists from discovery to the clinic.

PMID- 14579781
TI  - The role of chemokines in inflammatory skin diseases.

PMID- 14579782
TI  - Conservative management, gamma-knife radiosurgery, and microsurgery for acoustic
      neurinomas: a systematic review of outcome and risk of three therapeutic options.
AB  - Conservative management, gamma-knife (GK) radiosurgery, and microsurgery are
      therapeutic options for acoustic neurinomas (ANs). To determine the outcomes and
      risks of these methods this systematic review analyzed data from 903 patients
      with conservative management, 1475 with GK radiosurgery, and 5005 with
      microsurgery from 38 studies identified in MEDLINE searches. Conservative
      management over a 3.1-year period showed that 51% of ANs showed a tumor growth,
      an average tumor growth rate was 1.87 mm year-1, 20% of ANs ultimately required
      surgical intervention, and a third of the patients lost useful hearing. GK
      radiosurgery significantly reduced the percentage of ANs that enlarged, to 8%,
      and reduced the percentage that underwent microsurgery to 4.6% over a 3.8-year
      period. Microsurgery removed 96% of ANs totally, with tumor recurrence,
      mortality, and major disability rates of 1.8%, 0.63%, and 2.9%, respectively. The
      majority of ANs grow slowly, but ultimately require intervention. Carrying the
      risk of hearing loss, conservative management should be supplemented with close
      follow-up. With a low rate of morbidity, GK radiosurgery suppresses tumor growth
      and provides good tumor control. Microsurgery provides the best tumor control,
      although mortality and morbidity are not completely eliminated.

PMID- 14579783
TI  - Antiproliferative action of neomycin is associated with inhibition of cyclin D1
      activation in glioma cells.
AB  - The progression of mammalian cells through G1 phase of the cell cycle is governed
      by the D-type cyclins (D1, D2, D3). These proteins are induced at the beginning
      of the G1 phase and associate with serine/threonine cyclin-dependent kinases to
      form holoenzymes. Overexpression of cyclin D1 in human cancers as well as in
      several cancer cell lines has been reported. Here, we employed mitotic selection
      to synchronize the C6 glioma cell cycle at the start of the G1 phase and assessed
      the effects of neomycin on cyclin D1 protein detection by immunocytochemical
      analysis. Cyclin D1 activation as well as cell proliferation were already
      significantly reduced after 3 h of incubation of the cells with neomycin. These
      findings suggested that the antiproliferative effects of neomycin in gliomas
      could be mediated by inhibition of the expression of cyclin D1 gene and support
      further consideration of therapeutic use of neomycin in a Phase I clinical study
      for patients with recurrent glioblastoma.

PMID- 14579784
TI  - Chronic cerebral venous hypertension model in rats.
AB  - Although cerebral venous hypertension is known as an important determinant factor
      for clinical manifestation and outcome in patients with dural arteriovenous
      malformation (AVM), the pathophysiology of that condition is not well understood.
      We have created a chronic rat model by cervical arteriovenous fistularization
      with jugular vein occlusion and examined effect of cerebral venous hypertension
      on cerebral blood flow regulation. This model may be suitable for investigating
      mechanisms of cerebrovascular alteration after venous hypertension.

PMID- 14579786
TI  - Neurotrophic effect of hepatocyte growth factor on neonatal facial motor neurons.
AB  - The neurotrophic effect of hepatocyte growth factor (HGF) on axotomized facial
      motor neurons was examined after local application of HGF to the proximal facial
      nerve stump of the neonatal rat on post-natal day one (P1). Motor neuron survival
      was expressed as the neuronal cell count on the injured side as a percentage of
      that on the noninjured side. Motor neuron survival of the control group was 76%
      on P3, 54% on P5 and 23% on P8, that of the HGF-treated group 78% on P3, 69% on
      P5 and 31% on P8, and that of the brain-derived neurotrophic factor (BDNF)
      treated group 91% on P5 and 45% on P8. The motor neuron survival rates were then
      adjusted by deducting the facial motor neurons corresponding to the uninjured
      retroauricular branch (20%) of the facial nerve. The adjusted values were 70%
      (P3), 42% (P5) and 4% (P8) for the control group, 72% (P3), 61% (P5) and 14% (P8)
      for the HGF-treated group, and 88% (P5) and 32% (P8) for the BDNF-treated group.
      These findings demonstrate that HGF has a neuroprotective effect on injured
      facial motor neurons and suggest that HGF has neurotrophic properties distinct
      from those of BDNF.

PMID- 14579785
TI  - Geldanamycin reduces necrotic and apoptotic injury due to oxygen-glucose
      deprivation in astrocytes.
AB  - Recent data show that geldanamycin can protect the brain against stroke in vivo,
      and this may be due to induction of heat shock proteins. Our previous results
      show that heat shock protein 70 expression by retroviral transfection protects
      astrocytes from necrotic injury by combined oxygen-glucose deprivation, an in
      vitro model of ischemia. This study tested the ability of geldanamycin to protect
      astrocytes from either necrotic or apoptotic injury induced by oxygen-glucose
      deprivation. Astrocytes were pre-treated with 0.1 microgram ml-1 geldanamycin in
      the medium 4, 8, or 16 h before as well as during oxygen-glucose deprivation.
      Increased protein levels of heat shock protein 70 were observed after 8 h pre
      treatment with geldanamycin and increased further at 16 h pre-treatment, as
      detected by immunoblotting. Geldanamycin pre-treatment protected mature
      astrocytes from necrotic cell death and young astrocytes from apoptotic death.
      Geldanamycin protection of astrocytes against in vitro ischemia is likely due to
      upregulation of heat shock protein 70.

PMID- 14579787
TI  - Cerebrospinal fluid rhinorrhea: pathophysiological aspects and treatment.
AB  - The treatment of cerebrospinal fluid rhinorrhea is a challenge and requires a
      therapeutic strategy in order to reduce the risk of meningitis. The localization
      of the fistula is not always easy and direct surgical repair requires major
      operation with an outcome not always successful. In many patients, an alteration
      of CSF pressure and/or dynamics may be associated to the rhinorrhea, making its
      spontaneous or surgical closure difficult. In a series of 81 patients affected by
      rhinorrhea, we have studied the CSF pressure and dynamics and tried to stop the
      fistula by using a temporary or permanent CSF drainage. This procedure was able
      to cure the fistula in 54 cases, while a direct surgical repair was required in
      12 patients. In 13 cases both the procedures were required. Two patients refused
      any treatment. These results indicate that the study of the CSF pressure and
      dynamics may help to understand physiopathology of the CSF rhinorrhea and that
      the CSF drain (temporary or permanent) can be a simple way of definitively curing
      the CSF fistula in the majority of patients suffering from rhinorrhea.

PMID- 14579788
TI  - (-)Clausenamide improves long-term potentiation impairment and attenuates
      apoptosis after transient middle cerebral artery occlusion in rats.
AB  - The effects of (-)clausenamide (clau) on long-term potentiation (LTP) and
      neuronal DNA damage were investigated in a rat model of middle cerebral artery
      (MCA) occlusion. Four days after reperfusion, electrophysiology records revealed
      reduced LTP in the ipsilateral dentate gyrus of ischemic rats, while treatment
      with clau (10 mg kg-1 p.o. once daily) improved LTP impairment. The fractional
      increase of population spike amplitude 20-50 min after tetanus was significantly
      larger in ischemic rats treated with clau than vehicle treated animals. Terminal
      deoxynucleotidyltransferase mediated dUTP end labeling (TUNEL) assay revealed
      occurrence of apoptosis in the ipsilateral striatum. The numbers of TUNEL
      positive particles were significantly reduced after treatment with clau compared
      with vehicle group (78.8 +/- 17.9 versus 105.8 +/- 27.2). Mitochondrial rhodamine
      123 accumulation showed that clau treatment (55.0 +/- 8.5) elevated numbers of
      rhodamine 123-positive particles in the ipsilateral striatum compared with
      vehicle group (40.4 +/- 7.5) These results demonstrate that clau can improve LTP
      impairment in the ipsilateral dentate gyrus and enhance cell survival in the
      striatum compared to the vehicle-treated rats four days following ischemic damage
      and its protective effect on mitochondria may partially underlie its action.

PMID- 14579789
TI  - Immunohistochemical analysis of a cerebral arteriovenous malformation obliterated
      by radiosurgery and presenting with re-bleeding. Case report.
AB  - The purpose of this study was to analyze immunohistochemical characteristics of
      the cell population in a radiosurgically obliterated cerebral arteriovenous
      malformation (AVM) after recurrent hemorrhage. Immunohistochemical reactions were
      carried out on paraffin-embedded histological sections for von Willebrand factor
      (FVIII), CD34 endothelial antigen (CD34), vimentin and alpha-smooth-muscle actin
      (SMA) cytoskeletal proteins. Histopathological analysis revealed that the
      majority of AVM channels were replaced by hypocellular scar tissue. However some
      of them still disclosed thrombus organization by granulation tissue seven years
      after radiosurgery. FVIII and CD34 reactions revealed vessel neoformation in
      thromboses. Proliferating spindle-shaped cells with SMA and vimentin expression
      were identified in the granulation tissue. These histopathological findings
      suggest the role of re-canalization in recurrence of hemorrhage following
      radiosurgical obliteration of the AVM. Contribution of myofibroblastic elements
      in the vessels' occlusion after radiosurgery is also demonstrated.

PMID- 14579790
TI  - Cerebral and peripheral effects of laser needle-stimulation.
AB  - This study comprises scientific-theoretic fundamental investigations of
      laserneedle technology, a new and painless method of acupuncture stimulation.
      Laserneedles are not inserted in the skin, but are merely placed on the surface
      of the acupuncture point. The study documents the significant changes in
      peripheral microcirculation (p = 0.005) and surface temperature of the skin (p =
      0.02) induced by laser, in 22 healthy volunteers (mean age 24.4 +/- 2.6 years).
      In addition, a randomised cross-over study to characterise the specific changes
      in cerebral blood flow velocity with laserneedle acupuncture (p < 0.001) is
      presented. These results provide important information for characterising the
      effects of laserneedle acupuncture.

PMID- 14579792
TI  - Hypothalamic digoxin, hemispheric chemical dominance and syndrome X with multiple
      lacunar state. A hypothesis.
AB  - This study assessed the changes in digoxin and some other metabolites of the
      isoprenoid pathway in metabolic syndrome X presenting with multiple lacunar
      state. The isoprenoid pathway and digoxin status was also studied for comparison
      in individuals of differing hemispheric dominance to find out the role of
      cerebral dominance in the genesis of syndrome X. There was an increase in plasma
      HMG CoA reductase activity with a consequent increase in serum digoxin, which
      caused a reduction in RBC membrane Na(+)-K+ ATPase activity. There was an
      increase in serum tryptophan and its metabolites and a decrease in tyrosine and
      its metabolites. Serum magnesium was decreased with consequent alteration in the
      metabolism of glycosaminoglycans and glycolipids. Increase in dolichol, another
      product of the isoprenoid pathway, resulted in alteration in glycoprotein
      metabolism. Changes in the composition of membrane glycosaminoglycans,
      glycoproteins and cholesterol: phospholipid ratio were also observed in this
      disorder leading to decreased lysosomal stability. Decrease in ubiquinone,
      another isoprenoid metabolite, resulted in alteration in the free radical
      generation. Membrane Na(+)-K+ ATPase inhibition due to digoxin, altered membrane
      structure, increased tryptophan catabolites and decreased tyrosine catabolites
      can lead to increased intracellular calcium and reduced intracellular magnesium
      which can account for the symptoms of syndrome X. The biochemical patterns
      including hyperdigoxinemia observed in syndrome X correlated with those obtained
      in right hemispheric chemical dominance. Right hemispheric chemical dominance is
      a predisposing factor for syndrome X with multiple lacunar state.

PMID- 14579791
TI  - The temporal-spatial expression of VEGF, angiopoietins-1 and 2, and Tie-2 during
      tumor angiogenesis and their functional correlation with tumor neovascular
      architecture.
AB  - Angiopoietins play a pivotal role in tumor angiogenesis by modulating vascular
      endothelial proliferation and survival. The expression of angiopoietins 1 and 2
      (Ang-1 and Ang-2) and vascular endothelial growth factor (VEGF) has been
      documented in human malignant glioma. The expression of Ang-1, Ang-2, VEGF, and
      Tie-2, a member of the receptor tyrosine kinases and the natural receptor for
      both Ang-1 and Ang-2, follows a distinct transcriptional profile in vivo. Ang-2
      and VEGF were expressed early in tumor formation and their levels increased
      throughout tumor growth. Their expression coincided with the expansion of the
      tumor mass and the formation of the vascular tree. There was no significant
      change in the expression of Tie-2 and Ang-1. The expression of Ang-1 and Tie-2
      was more noticeable at the periphery of the tumor. The expression of Ang-2 was
      more robust at the periphery and within the tumor mass, and VEGF was more
      concentrated within the center of the tumor. This distinct expression profile may
      explain the morphology of the newly formed vessels at various times and regions
      of the tumor. The lack of concomitant expression of Ang-1 may underscore the
      unopposed endovascular induction by Ang-2 and VEGF resulting in the chaotic
      appearance and fragility of tumor vessels.

PMID- 14579793
TI  - Increased incidence of thrombophilic abnormalities in patients with cranial dural
      arteriovenous fistulae.
AB  - Cranial dural arteriovenous fistulae (DAVF) may occur post-traumatic or sporadic.
      The physiopathologic mechanisms of sporadic DAVF are still unclear. A dural sinus
      thrombosis followed by an increase in venous pressure and/or an increased
      procoagulatory activity of the coagulation system are associated at least with
      some DAVF. The objective of this study was to investigate the coagulation profile
      in patients with DAVF. Thus the association of thrombophilic abnormalities, sinus
      thrombosis and DAVF should be analyzed. A total of 15 patients with cranial DAVF
      were included in this study. Blood samples were analyzed for 20210A mutation of
      the prothrombin gene, resistance to activated protein C and factor V Leiden
      mutation. Fibrinogen (Fib), Textarin time (TT), antithrombin (AT), protein C and
      protein S activity, von Willebrand factor antigen (vWF:Ag), Ristocetin cofactor
      activity (vWF:RCo), D-Dimer (DD) and coagulation factor VIII-activity (F VIII)
      were determined in all patients. Blood was screened for the occurrence of lupus
      antiphospholipid antibodies and cardiolipin antibodies. Thrombophilic risk
      factors were found in 5 (33%) of the 15 patients with cranial DAVF. Four patients
      had a heterozygote 20210A mutation of the prothrombin gene and one patient had a
      heterozygote FV Leiden mutation. Sinus thrombosis was detected in two patients
      with grade 2b DAVF and was associated with a 20210A mutation of the prothrombin
      gene in both patients. Additionally, one patient had deficient protein C activity
      and screening for cardiolipin antibodies was positive in three patients. In the
      current series the frequency of prothrombin Gene 20210A mutation was higher in
      patients with DAVF compared to the general population, whereas the incidence of
      Factor V Leiden mutation was not. Therefore in patients with cranial DAVF
      thrombophilic abnormalities should be considered in the post-operative/post
      interventional management.

PMID- 14579794
TI  - Antioxidant properties of carvedilol: inhibition of lipid peroxidation, protein
      oxidation and superoxide generation.
AB  - Oxidative stress has been suggested to be an etiological factor in cerebro- and
      cardiovascular disorders. We examined antioxidant activities of carvedilol, a
      beta- and alpha-adrenoreceptor blocker. Carvedilol suppressed lipid auto
      oxidation and protein carbonyl formation in brain homogenate in a dose-dependent
      manner. Carvedilol also suppressed superoxide generation of human neutrophils.
      These properties of carvedilol should be suitable for treating hypertension
      resulting in cerebro- and cardiovascular diseases.

PMID- 14579795
TI  - 17 Beta-estradiol suppresses AMPA-induced increases in regional cerebral O2
      consumption.
AB  - We tested the hypothesis that 17 beta-estradiol would reduce the cerebral O2
      consumption response resulting from glutamate receptor stimulation by alpha amino
      3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA). Fourteen ovariectomized rats
      were separated into 17 beta-estradiol (0.5 mg 21 day release pellet) and control
      (placebo pellet) groups to determine cerebral blood flow (14C-iodoantipyrine) and
      O2 consumption (microspectrophotometry). After topical cortical stimulation with
      10(-3) M and 10(-4) M AMPA, cerebral blood flow increased significantly in both
      groups in a concentration-dependent manner. Cerebral O2 extraction was not
      significantly different in any region of the 17 beta-estradiol treated group. In
      the placebo treated group, the O2 extraction in the saline treated cortex and in
      the 10(-3) M AMPA treated cortex was significantly higher when compared to the
      10(-4) M AMPA treated cortex. Cerebral O2 consumption in the control group
      increased by 20%, from 5.2 +/- 0.6 to 6.1 +/- 0.7, with 10(-4) M AMPA and
      significantly increased by 64% to 8.5 +/- 0.8 ml O2 min-1 100 g-1 with 10(-3) M
      AMPA. The 17 beta-estradiol group demonstrated no statistically significant
      difference in O2 consumption between the saline treated and AMPA treated cortex.
      Thus, 17 beta-estradiol reduced the effects of AMPA in increasing cerebral O2
      consumption.

PMID- 14579796
TI  - Different actions of gamma-hydroxybutyrate: a critical outlook.
AB  - Gamma-hydroxybutyrate acid (GHB) is a naturally occurring analog of GABA in the
      mammalian brain and can be therapeutically used for basic sedation in intensive
      care units. Although its application is discussed controversially, GHB is
      suspected to protect neuronal tissue against ischemic damage. GHB was tested for
      an acute effect on electrophysiologic parameters of guinea pig hippocampal
      tissues exposed to ischemic conditions. With application of 0.5 mM GHB, an acute
      protective effect was observed. The aim of the present paper is to discuss our
      experimental results as well as pathophysiological mechanisms of GHB and its
      clinical applicability.

PMID- 14579797
TI  - Lipidized or lipomatous meningioma, which is more appropriate? A case report.
AB  - Lipoblastic, lipomatous or lipidized meningioma is an unusual extra-axial benign
      tumor. It shows benign clinical features and has a good prognosis after surgical
      excision. We present a 54-year-old woman with intracranial lipidized meningioma
      in the right temporal fossa, discuss the importance of the differential diagnosis
      among similar tumors and discuss the term 'Lipidized meningioma' in the light of
      the literature.

PMID- 14579798
TI  - Proliferation of a subpopulation of reactive astrocytes following needle
      insertion lesion in rat.
AB  - It is well known that traumatic injuries of the CNS induce a gliotic reaction,
      characterized by the presence of reactive astrocytes. Reactive astrocytes exhibit
      enhanced expression of the astrocyte-specific intermediate filament, glial
      fibrillary acidic protein (GFAP), hypertrophy, and thickened processes. Recently,
      we have demonstrated that injuries of the CNS induce a re-expression of an
      embryonic intermediate filament-associated protein, IFAP-70/280 kDa. Based on
      IFAP-70/280 kDa immunolabeling, we have shown that reactive astrocytes, activated
      by stab-wound injury, can be divided into two major groups: 1. persistent
      IFAP+/GFAP+ cells which are close to the wound in the area of glial scar, and 2.
      transient IFAP-/GFAP+ cells which are farther from the wound. In this study, we
      use BrdU incorporation to examine proliferation in these two groups of reactive
      astrocytes induced by stab injury of the rat cerebrum. Triple/double-label
      immunofluorescence microscopy was performed using antibodies to IFAP-70/280 kDa,
      GFAP, and BrdU. The results showed that BrdU+ reactive astrocytes (GFAP+) were
      always IFAB-70/280 kDa+ as well. However, not all IFAP+ reactive astrocytes are
      BrdU+. BrdU+ signal was not observed in any IFAP- reactive astrocytes. At five
      days post-lesion, IFAP+ reactive astrocytes were increasing in the area of the
      wound (0-50 micrograms from the wound edge), but had reached a peak in the
      proximal area (50-800 micrograms away from the wound edge). At eight days post
      lesion, IFAP+ reactive astrocytes achieved the highest percentage in the wound
      area. At the same time, BrdU-containing reactive astrocytes occupied an area
      closer to the wound. By 20 days post-lesion, following the formation of the
      gliotic scar at the stab-wound, a few IFAP+/GFAP+ cells still persisted. BrdU
      containing reactive astrocytes were only observed in the scar. These results
      indicate that many IFAP+ reactive astrocytes close to the wound, in contrast to
      the IFAP- ones farther from the wound, appear to regain their proliferative
      potential to increase in number and participate in the formation of the gliotic
      scar.

PMID- 14579799
TI  - Fighting for health.

PMID- 14579800
TI  - The return to authenticity.

PMID- 14579801
TI  - Congruence matters: a consideration of adaptation and appropriateness.

PMID- 14579802
TI  - Healing our lives.

PMID- 14579803
TI  - The intention of living fully: an alternative to fighting cancer.

PMID- 14579804
TI  - Does "fighting spirit" improve medical outcomes of cancer patients?

PMID- 14579805
TI  - Healing as an adventure.

PMID- 14579806
TI  - The unity of mind, body, and spirit: a five element view of cancer.

PMID- 14579807
TI  - Living in relation to mystery: addressing mind, body, and spirit.

PMID- 14579808
TI  - A model of hypnotic intervention for palliative care.
AB  - The World Health Organization defines palliative care as "the active total care
      of patients whose disease is not responsive to curative treatment." One of the
      primary issues of palliative care for patients with advanced cancer is symptom
      control and quality-of-life issues. The purpose of the hypnotic model presented
      here is to improve the patient's total psychological, social, and spiritual well
      being. There exists a need for a broad and inclusive model of mind-body
      interventions for palliative care. This is supported by the observation that
      symptoms related to psychological distress and existential concerns are even more
      prevalent than pain and other physical symptoms among those with life-limiting
      conditions. The following model integrates naturalistic, solution-oriented
      hypnosis within the framework of a situational 4-stage crisis matrix. The four
      stages of the matrix are: (1) The Initial Crisis, (2) Transition, (3) Acceptance,
      and (4) Preparation for Death. Hypnotic interventions are tailored to each stage
      in the crisis matrix.

PMID- 14579809
TI  - Protection for manufacturing, not research.

PMID- 14579810
TI  - Vaccines of the future.

PMID- 14579812
TI  - Choosing a career in private or corporate patent practice.

PMID- 14579811
TI  - Rosuvastatin calcium.

PMID- 14579813
TI  - Disseminated vaccinia false alarm.
AB  - We report the case of a 6-year-old girl who presented in December 2002 with fever
      and a vesicular rash. Initially she was diagnosed with Stevens-Johnson syndrome.
      The differential diagnosis was expanded, however, when an exposure to a person
      who was believed to be vaccinated recently against smallpox was revealed. We
      describe the sequence of events that ensued and the workup for a possible case of
      disseminated virus.

PMID- 14579814
TI  - Kaposi sarcoma with upper airway obstruction and bilateral chylothoraces.
AB  - A 3-year-old boy infected with HIV presented with progressive dyspnea and upper
      airway obstruction necessitating airway stenting. Chest radiography revealed
      bilateral alveolar opacification and chylothoraces. Post,mortem examination
      confirmed disseminated Kaposi sarcoma with infiltration of the thoracic duct.

PMID- 14579815
TI  - Challenges to health service development in Iraq.

PMID- 14579816
TI  - Missing people and mass graves in Iraq.

PMID- 14579817
TI  - Medical education and training in Iraq.

PMID- 14579818
TI  - Successful cidofovir treatment of adenovirus-associated hemorrhagic cystitis and
      renal dysfunction after allogenic bone marrow transplant.
AB  - We present a patient who developed hemorrhagic cystitis and renal dysfunction
      after unrelated bone marrow transplantation. Polyoma BK virus and adenovirus 11
      were detected in the urine. Vidarabine was administered without effect.
      Relatively low dose cidofovir was efficacious. Renal function improved, and the
      urinary secretion of adenovirus stopped.

PMID- 14579819
TI  - Invasive group A streptococcal infection after tonsillectomy.
AB  - Tonsillectomy is a very common procedure in childhood. Infectious complications
      after tonsillectomy are infrequently reported. We describe two children with
      severe group A beta-hemolytic streptococcal infection after tonsillectomy, and we
      review the literature about bacteremia and infectious complications after
      tonsillectomy.

PMID- 14579820
TI  - Basal ganglia involvement in a child with cat-scratch disease.
AB  - Catch-scratch disease (CSD) is a self-limiting zoonotic illness. Encephalopathy
      is the most common neurologic manifestation of CSD. Neuroimaging is usually
      normal with occasional abnormalities reported in children involving the cerebral
      cortex and thalamus but not previously described in the basal ganglia. Here we
      report a 7-year-old boy with CSD encephalopathy who developed choreoathetosis
      with high intensity changes in basal ganglia on magnetic resonance imaging scan.

PMID- 14579821
TI  - Newborn with suppurative nasal discharge.

PMID- 14579822
TI  - Vesicouterine fistula and blind vagina.

PMID- 14579823
TI  - [Today and tomorrow on the study of prostate cancer].

PMID- 14579825
TI  - The health education work of the Hadassah Zionist women's organization in
      Palestine during the British Mandate 1918-1948.

PMID- 14579826
TI  - Professor Nathan Saltz and surgery in Israel.

PMID- 14579824
TI  - The birth of the Israel health care system: an American mother and a Russian
      father.

PMID- 14579827
TI  - The American Physicians Fellowship for medicine in Israel: a half century of
      support.

PMID- 14579828
TI  - Developing Israel's health system: the contribution of the American Jewish Joint
      Distribution Committee.
AB  - The American Jewish Joint Distribution Committee (JDC) has been involved in
      developing Israel's health services since 1914. The types of involvement and
      major accomplishments in service development are summarized in Apprendix 1. Over
      the years, as needs changed and as the service environment expanded, JDC adapted
      its activities in order to remain a leading force in developing new and
      innovative services for Israel's most vulnerable populations.

PMID- 14579829
TI  - Americans at Ben-Gurion University of the Negev (BGU).

PMID- 14579830
TI  - On several American physicians and their impact on the Hebrew University Hadassah
      Medical School.

PMID- 14579831
TI  - Precious stones in Jewish and Christian medieval literature: natural and/or
      occult sciences?

PMID- 14579832
TI  - Anxiety in Jewish sources.

PMID- 14579833
TI  - How effective were cough remedies known to medieval Egyptians.

PMID- 14579834
TI  - Adam Politzer (1835-1920).

PMID- 14579835
TI  - Drowning not waving.

PMID- 14579836
TI  - [Comparative quality management].

PMID- 14579837
TI  - [Admission of slot-time contracts for anesthetists with personnel release].

PMID- 14579838
TI  - [Origin and development of carcinoma of the prostate].

PMID- 14579839
TI  - Knee trauma: cruciate ligament dysplasia associated with fibular hemimelia
      (2003:7b).

PMID- 14579840
TI  - A complex anterior mediastinal mass (2003:10a).

PMID- 14579841
TI  - Revisiting fitness and fatness as predictors of mortality.

PMID- 14579842
TI  - Effects of stretching on muscle soreness and risk of injury: a meta-analysis.

PMID- 14579843
TI  - Arthroscopic intervention to reduce pain and improve function in knee
      osteoarthritis.

PMID- 14579844
TI  - Extracorporeal shock wave therapy for lateral epicondylitis.

PMID- 14579845
TI  - [Left ventricular dysfunction in Churg-Strauss syndrome].
AB  - Churg-Strauss syndrome is a rare disorder characterized by hypereosinophilia and
      a systemic vasculitis occurring inpatients with asthma and allergic rhinitis.
      Vasculitis commonly affects the lungs, the heart, the skin, and the peripheral
      nervous system. Cardiac involvement is characterized by acute and constrictive
      pericarditis, myocarditis and endocarditis, as well as ischemic cardiomyopathy.
      Endomyocardial fibrosis similar to Loeffler's syndrome has been rarely described.
      In the presented case, a 43 year old man with a history of allergy and asthma
      suffered from increasing dyspnea, fever, pulmonary infiltates and cardiomyopathy.
      Laboratory studies were notable for marked hypereosinophilia. In a bronchoscopic
      lavage and transbronchial biopsy eosinophilic infiltrates accompanied by
      vasculitis were found, Churg-Strauss syndrome was diagnosed. Echocardiogram
      showed endomyocardial deposits in the apex of the right ventricle, right
      ventricular function was normal particular in the basal segments. The left
      ventricle was slightly enlarged and left ventricular function was impaired. The
      diastolic mitral in-flow showed a restrictive pattern. Additionally, a
      pericardial effusion was observed without signs of tamponade. The patient
      received corticosteroids, cyclophosphamide and cardiomyopathy-specific therapy
      and showed a marked improvement after 4 months.

PMID- 14579846
TI  - Radiation-induced coronary artery disease.
AB  - Radiation-induced heart disease must be considered in any patient with cardiac
      symptomatology who had prior mediastinal irradiation. Radiation can affect all
      the structures in the heart, including the pericardium, the myocardium, the
      valves and the conduction system. In addition to these pathologies, coronary
      artery disease following mediastinal radiotherapy is the most actual cardiac
      pathology as it may cause cardiac emergencies requiring interventional
      cardiological or surgical interventions. Case A 36-year-old man was admitted to
      the clinic with unstable angina pectoris of one month duration. The patient had
      no coronary artery disease risk factor. The history of the patient revealed that
      he had mediastinal radiotherapy due to Hodgkin's disease at 10-year of age.
      Coronary arteriography showed total occlusion of the left anterior descending
      artery and 70% stenosis of the proximal right coronary artery. Both arteries are
      dilated with placement of two stents. Control coronary arteriography at the end
      of the first year showed patency of both stents and the patient is free of
      symptoms. Previous radiotherapy to the mediastinum should be considered as a risk
      factor for the development of premature coronary artery disease. Percutaneous
      transluminal coronary angioplasty with stent placement or surgical
      revascularization are the preferred methods of treatment. Preoperative assessment
      of internal thoracic arteries should be considered prior to surgery. As the
      radiation therapy is currently the standard treatment for a number of mediastinal
      malignancies, routine screening of these patients and optimal cardiac prevention
      during radiotherapy are the only ways to minimize the incidence of radiation
      induced heart disease.

PMID- 14579847
TI  - Mitral valve endocarditis: an uncommon cause of myocardial infarction.
AB  - A 39 year old woman presented with acute anterior myocardial infarction. At
      coronary angiography the distal left anterior descending coronary artery (LAD)was
      occluded despite otherwise normal coronary arteries. The LAD was successfully
      recanalized using PTCA. Subsequently, a transesophageal echocardiogram revealed
      vegetations and a significant incompetence of the mitral valve. Blood cultures
      identified out enterococcus faecalis. Despite intra-venous antibiotic treatment
      guided by sensitivity testing, the patient ultimately required elective mitral
      valve replacement. During a prior outpatient diagnostic work-up of fever/malaise,
      the diagnosis of infective endocarditis was not made.This case conveys two main
      messages: 1) because the history and physical sings of bacterial endocarditis can
      be subtle or non-specific, the first step to diagnose infective endocarditis is
      to include it in the differential diagnosis. 2) Percutaneous coronary
      intervention is an effective treatment of septic embolic occlusion of a major
      coronary artery.

PMID- 14579848
TI  - [Proctological diseases in routine urologic practice].
AB  - Nearly two third of adults will suffer from proctologic complaints. The same
      symptoms could also indicate or mask an anorectal carcinoma. Therefore, the first
      priority should be to exclude the possibility of a neoplasm of the colon, rectum
      and the anal canal. Knowledge of the specific anatomy of the anal canal and the
      patient's history will lead to an exact proctologic diagnosis: perianal
      thrombosis, acute thrombosed prolapsed haemorrhoidal plexus, an anal fissure,
      abscess and fistula are located within the highly sensitive anoderma and are
      characterized by pain. Perianal thrombosis, chronic fissure, abscess and fistula
      require surgery. Conservative treatment is the choice for an acute anal fissure,
      haemorrhoids grade I-II. Haemorrhoids II-III require surgery, e.g. by
      haemorrhoidal artery ligation, open or closed resection of the haemorrhoidal
      plexus, reconstruction of the anal canal or stapled mucosectomy. Perianal
      diseases such as perianal tags, fibroma or condylomata acuminata are easily
      diagnosed and treated. Secondary perianal eczema requires treatment of the
      underlying proctologic disease. If it persists, a biopsy is required.

PMID- 14579849
TI  - Lumen and the liver--together again in NASHville.

PMID- 14579850
TI  - Systemic FK506 and post transplant food allergy in children.

PMID- 14579851
TI  - Staging of abdominal metastases in pancreatic carcinoma by diagnostic laparoscopy
      and magnetic resonance imaging.
AB  - BACKGROUND: Different noninvasive and invasive techniques are available for the
      detection of abdominal metastases in pancreatic carcinoma. Since small hepatic or
      peritoneal metastases are a crucial problem which precludes resection, accurate
      detection is mandatory. We compared laparoscopic staging of abdominal metastases
      in adenocarcinoma of the pancreas with MRI. METHODS: 55 patients with pancreatic
      adenocarcinoma had been screened and 49 entered the retrospective study. All
      patients had undergone MRI of the upper abdomen with concomitant MR
      cholangiopancreatography (MRCP) and diagnostic laparoscopy under conscious
      sedation. Patients without histologic proof of abdominal metastases underwent
      laparotomy. RESULTS: In 6/10 patients, metastases were correctly detected by
      laparoscopy, yielding a sensitivity of 60% and a specificity of 92%.MRI predicted
      metastases in 6/10 patients with 60% sensitivity and 100% specificity.
      Laparoscopy showed metastases in 3 patients that were missed by MRI, but failed
      to identify metastases in 3 of 6 patients with metastases on MRI. Though only one
      patient showed previously undetected metastases during laparotomy, 3 patients
      with abdominal metastases underwent unnecessary laparotomy due to a lack of
      histologic proof of malignancy. CONCLUSIONS: Whereas diagnostic laparoscopy is
      sensitive for the detection of small metastases and offers histologic
      verification, intrahepatic alterations are not detectable by sole visual
      inspection.MRI may compensate for this deficiency, but histologic proof of
      malignancy may be problematic. To date, no definite decision in favor of one of
      the presented procedures for the staging of abdominal metastases can be given.

PMID- 14579852
TI  - [Comments on the article by Mydlika et al, on the treatment of ethylene glycol
      poisoning].

PMID- 14579853
TI  - Digital x-ray tomosynthesis: current state of the art and clinical potential.
AB  - Digital x-ray tomosynthesis is a technique for producing slice images using
      conventional x-ray systems. It is a refinement of conventional geometric
      tomography, which has been known since the 1930s. In conventional geometric
      tomography, the x-ray tube and image receptor move in synchrony on opposite sides
      of the patient to produce a plane of structures in sharp focus at the plane
      containing the fulcrum of the motion; all other structures above and below the
      fulcrum plane are blurred and thus less visible in the resulting image.
      Tomosynthesis improves upon conventional geometric tomography in that it allows
      an arbitrary number of in-focus planes to be generated retrospectively from a
      sequence of projection radiographs that are acquired during a single motion of
      the x-ray tube. By shifting and adding these projection radiographs, specific
      planes may be reconstructed. This topical review describes the various
      reconstruction algorithms used to produce tomosynthesis images, as well as
      approaches used to minimize the residual blur from out-of-plane structures.
      Historical background and mathematical details are given for the various
      approaches described. Approaches for optimizing the tomosynthesis image are
      given. Applications of tomosynthesis to various clinical tasks, including
      angiography, chest imaging, mammography, dental imaging and orthopaedic imaging,
      are also described.

PMID- 14579854
TI  - Conductivity and current density image reconstruction using harmonic Bz algorithm
      in magnetic resonance electrical impedance tomography.
AB  - Magnetic resonance electrical impedance tomography (MREIT) is to provide cross
      sectional images of the conductivity distribution sigma of a subject. While
      injecting current into the subject, we measure one component Bz of the induced
      magnetic flux density B = (Bx, By, Bz) using an MRI scanner. Based on the
      relation between (inverted delta)2 Bz and inverted delta sigma, the harmonic Bz
      algorithm reconstructs an image of sigma using the measured Bz data from multiple
      imaging slices. After we obtain sigma, we can reconstruct images of current
      density distributions for any given current injection method. Following the
      description of the harmonic Bz algorithm, this paper presents reconstructed
      conductivity and current density images from computer simulations and phantom
      experiments using four recessed electrodes injecting six different currents of 26
      mA. For experimental results, we used a three-dimensional saline phantom with two
      polyacrylamide objects inside. We used our 0.3 T (tesla) experimental MRI scanner
      to measure the induced Bz. Using the harmonic Bz algorithm, we could reconstruct
      conductivity and current density images with 82 x 82 pixels. The pixel size was
      0.6 x 0.6 mm2. The relative L2 errors of the reconstructed images were between
      13.8 and 21.5% when the signal-to-noise ratio (SNR) of the corresponding MR
      magnitude images was about 30. The results suggest that in vitro and in vivo
      experimental studies with animal subjects are feasible. Further studies are
      requested to reduce the amount of injection current down to less than 1 mA for
      human subjects.

PMID- 14579855
TI  - The effect of the Varian amorphous silicon electronic portal imaging device on
      exit skin dose.
AB  - Measurements have been made of the increase in exit surface dose resulting from
      backscattered radiation generated by the Varian amorphous silicon electronic
      portal imaging device (EPID). An increase of < or = 14% was demonstrated at both
      6 MV and 10 MV, in a manner which suggests that backscatter from the EPID acts to
      re-establish electronic equilibrium at the exit surface, normally absent in the
      build-down region. The magnitude of this effect was influenced by field size,
      measurement depth and exit surface to EPID distance. Assuming typical constraints
      of portal imaging frequency and geometry, the results suggest that EPID generated
      backscatter is unlikely to alter the frequency or severity of exit skin
      reactions. However, the results do suggest that a limit on the minimum separation
      between the EPID and the exit surface should be set, and that similar
      investigations should be made for other EPID models.

PMID- 14579857
TI  - The relationship of temperature rise to specific absorption rate and current in
      the human leg for exposure to electromagnetic radiation in the high frequency
      band.
AB  - Of the biological effects of human exposure to radiofrequency and microwave
      radiation, the best-established are those due to elevation of tissue temperature.
      To prevent harmful levels of heating, restrictions have been proposed on the
      specific absorption rate (SAR). However, the relationship between SAR and
      temperature rise is not an invariant, since not only the heat capacity but also
      the efficiency of heat dissipation varies between different tissues and exposure
      scenarios. For small enough SAR, the relationship is linear and may be
      characterized by a 'heating factor' deltaT/SAR. Under whole-body irradiation the
      SAR may be particularly high in the ankles due to the concentration of current
      flowing through a relatively small cross-sectional area. In a previous paper, the
      author has presented calculations of the SAR distribution in a human leg in the
      high frequency (HF) band. In this paper, the heating factor for this situation is
      derived using a finite element approximation of the Pennes bioheat equation. The
      sensitivity of the results to different blood perfusion rates is investigated,
      and a simple local thermoregulatory model is applied. Both time-dependent and
      steady-state solutions are considered. Results confirm the appropriateness of the
      ICNIRP reference level of 100 mA on current through the leg, but suggest that at
      higher currents significant thermoregulatory adjustments to muscle blood flow
      will occur.

PMID- 14579856
TI  - Response of LiF-TLD micro-rods around 125I radioactive seed.
AB  - The EGSnrc Monte Carlo system has been used to calculate the energy response of
      LiF-TLDs of different sizes around 125I permanent brachytherapy sources. The
      source model includes the effects of an encapsulation, self-absorption within the
      source and in the welded ends of the encapsulation. The LiF-TLD material has
      cylindrical geometry (micro-rod) with diameters ranging from 1 mm to 5 mm and a
      length of 6 mm. The energy response factor (relative to 60(Co gamma-rays) for a
      LiF-TLD calibrated in 60Co gamma-rays and then irradiated by an 125I permanent
      brachytherapy source varies between 1.32 +/- 0.2% (1 SD) and 1.406 +/- 0.2% (1
      SD) for 5 mm and 1 mm diameter micro-rods, respectively. The energy response
      factor depends on the radius and the polar angle (r, theta) of the measurement
      point. For a LiF-TLD of diameter 1 mm calibrated at 1 cm on the transverse axis
      (r = 1.0 cm, theta = 90) of the 125I source in water, the energy response factor
      decreases by a maximum of 3.5% within the 6 cm x 6 cm x 6 cm calculation region.
      For the 5 mm diameter LiF-TLD, the energy response factor decreases by a maximum
      of 5% in the same region. An examination of the photon energy spectra showed that
      the photon spectrum does not change significantly in water within the 3D
      calculation region (6 cm x 6 cm x 6 cm). The mass energy absorption coefficient
      ratio of water to LiF-TLDs does not vary by more than 0.5% in this calculation
      grid. The results, however, show that there is a change in the photon spectrum
      with distance from the source and with polar angle for LiF-TLDs. This difference
      in the energy spectrum gives rise to a difference in the mass energy absorption
      coefficient ratio of water to LiF (calculated by taking into account the
      difference in photon fluence in water and LiF) and that calculated assuming that
      the photon spectrum in water and in the LiF-TLD is identical.

PMID- 14579858
TI  - A semi-automatic method for developing an anthropomorphic numerical model of
      dielectric anatomy by MRI.
AB  - Complex permittivity values have a dominant role in the overall consideration of
      interaction between radiofrequency electromagnetic fields and living matter, and
      in related applications such as electromagnetic dosimetry. There are still some
      concerns about the accuracy of published data and about their variability due to
      the heterogeneous nature of biological tissues. The aim of this study is to
      provide an alternative semi-automatic method by which numerical dielectric human
      models for dosimetric studies can be obtained. Magnetic resonance imaging (MRI)
      tomography was used to acquire images. A new technique was employed to correct
      nonuniformities in the images and frequency-dependent transfer functions to
      correlate image intensity with complex permittivity were used. The proposed
      method provides frequency-dependent models in which permittivity and conductivity
      vary with continuity--even in the same tissue--reflecting the intrinsic realistic
      spatial dispersion of such parameters. The human model is tested with an FDTD
      (finite difference time domain) algorithm at different frequencies; the results
      of layer-averaged and whole-body-averaged SAR (specific absorption rate) are
      compared with published work, and reasonable agreement has been found. Due to the
      short time needed to obtain a whole body model, this semi-automatic method may be
      suitable for efficient study of various conditions that can determine large
      differences in the SAR distribution, such as body shape, posture, fat-to-muscle
      ratio, height and weight.

PMID- 14579859
TI  - Influence of setup errors on spinal cord dose and treatment plan quality for
      cervical spine tumours: a phantom study for photon IMRT and heavy charged
      particle radiotherapy.
AB  - Tumours partly surrounding the cervical spine may be treated by conformal
      radiotherapy (RT) using intensity-modulated RT (IMRT) with photons or heavy
      charged particle RT. For both, a high setup accuracy is required to spare the
      radiosensitive spinal cord, if a high dose is to be delivered. A phantom study
      was performed to determine the variation of the dose to the spinal cord surface
      by predefined setup errors. The measured doses were compared to those calculated
      by the treatment planning programme. The influence of systematic setup errors on
      characteristic parameters of the treatment plan quality was quantified. The
      largest variation of the mean and maximum doses to the spinal cord due to setup
      errors was significantly larger for carbon ions than for IMRT (mean: 11.9% versus
      3.9%, max: 29.2% versus 10.8% of the prescribed dose). For the comparison of
      measured and calculated doses, mean deviations of 3% (IMRT) and 6% (carbon ions)
      of the prescribed dose were obtained. These deviations have to be considered,
      when the spinal cord dose is assessed from the treatment plan and they may also
      influence the dose prescription. Carbon ions yield better values for coverage
      (99.9% versus 93.1%) and conformality (110% versus 126%) of the PTV as compared
      to IMRT, while the spinal cord is better spared. Dose distributions produced with
      carbon ions, however, are more sensitive to setup errors, which have to be
      considered during treatment.

PMID- 14579860
TI  - Algorithm and performance of a clinical IMRT beam-angle optimization system.
AB  - This paper describes the algorithm and examines the performance of an intensity
      modulated radiation therapy (IMRT) beam-angle optimization (BAO) system. In this
      algorithm successive sets of beam angles are selected from a set of predefined
      directions using a fast simulated annealing (FSA) algorithm. An IMRT beam-profile
      optimization is performed on each generated set of beams. The IMRT optimization
      is accelerated by using a fast dose calculation method that utilizes a
      precomputed dose kernel. A compact kernel is constructed for each of the
      predefined beams prior to starting the FSA algorithm. The IMRT optimizations
      during the BAO are then performed using these kernels in a fast dose calculation
      engine. This technique allows the IMRT optimization to be performed more than two
      orders of magnitude faster than a similar optimization that uses a convolution
      dose calculation engine. Any type of optimization criterion present in the IMRT
      system can be used in this BAO system. An objective function based on clinically
      relevant dose-volume (DV) criteria is used in this study. This facilitates the
      comparison between a BAO plan and the corresponding plan produced by a planner
      since the latter is usually optimized using a DV-based objective function. A
      simple prostate case and a complex head-and-neck (HN) case were used to evaluate
      the usefulness and performance of this BAO method. For the prostate case we
      compared the BAO results for three, five and seven coplanar beams with those of
      the same number of equispaced coplanar beams. For the HN case we compare the BAO
      results for seven and nine non-coplanar beams with that for nine equispaced
      coplanar beams. In each case the BAO algorithm was allowed to search up to 1000
      different sets of beams. The BAO for the prostate cases were finished in about 1
      2 h on a moderate 400 MHz workstation while that for the head-and-neck cases were
      completed in 13-17 h on a 750 MHz machine. No a priori beam-selection criteria
      have been used in achieving this performance. In both the prostate and the head
      and-neck cases, BAO is shown to provide improvements in plan quality over that of
      the equispaced beams. The use of DV-based objective function also allows us to
      study the dependence of the improvement of plan quality offered by BAO on the DV
      criteria used in the optimization. We found that BAO is especially useful for
      cases that require strong DV criteria. The main advantages of this BAO system are
      its speed and its direct link to a clinical IMRT system.

PMID- 14579861
TI  - Prediction of normal tissue response and individualization of doses in
      radiotherapy.
AB  - In this work we estimate the therapeutic gain that could be obtained using a
      radiotherapy programme in which doses were based on a radiosensitivity test that
      was able to predict the final response of normal tissues to radiation for each
      particular patient. To date, no good radiosensitivity assay has been demonstrated
      and by way of example we use an assay based on initial DNA damage. The
      individualized programme we propose is based on an increase in the dose delivered
      to patients showing a resistant behaviour to radiation and on the adoption of
      alternative programmes or a careful monitoring of those patients in whom an
      excessive reaction is expected. To quantify the results produced by the
      individualization programme, both analytical and Monte Carlo simulation methods
      are used. The increase in tumour control probability obtained by means of this
      individualization strongly depends on the dose-response curve for the particular
      tumour. In certain cases, this enhancement can be marked, and 40% of the patients
      considered in this work could attain more than 10% increase in tumour control
      probability. The quantitative estimations in this study indicate the need to seek
      a predictive assay of radiosensitivity, for both normal and tumour tissue
      response, in order to develop individualized treatment protocols.

PMID- 14579862
TI  - Transit time kinetics in ordered and disordered vascular trees.
AB  - Imaging modalities exploit tracer-dilution methods to measure bulk haemodynamic
      parameters such as blood flow and volume at the level of the microcirculation.
      Here, we ask the question of whether the kinetics of a tracer can reveal
      morphological information about the vessels through which the tracers flow. The
      goal is to relate the acquired time-intensity characteristic to details of the
      vascular structure that lies below the imaging resolution. Two fractal vascular
      models are developed that represent organized 'kidney-like' and disorganized
      'tumour-like' structures. The models are generated using simple rules of
      branching and fractal geometry in two dimensions. Blood flow and tracer kinetics
      are simulated using fundamental laws of haemodynamics. The flow conditions are
      matched in the two models. The fractal box dimensions of the kidney (D(B) = 1.67
      +/- 0.01) and the tumour (D(B) = 1.80 +/- 0.01) vasculatures fall in the range
      given in the literature (D(B) = 1.61 +/- 0.06 and D(B) = 1.84 +/- 0.04,
      respectively). The tracer kinetic curves of the kidney and the tumour
      vasculatures have the same initial slope and final asymptote, corresponding to
      the same flow rate and vascular volume, but have different forms. The difference
      in the two curves is related to the distribution function of transit times of the
      vascular models, and is a consequence of the randomness introduced in vessel
      diameter and length. In principle, the form of the tracer kinetic curve from a
      contrast imaging study may offer information relating not only to vascular volume
      and flow rate, but also to the organization of a microvascular network.

PMID- 14579864
TI  - Science and sports: securing the bridge.

PMID- 14579863
TI  - Free of speckle ultrasonic imaging of soft tissue with account of second harmonic
      signal.
AB  - The Born approximation deconvolved inverse scattering imaging technique is an
      alternative to the conventional pulse-echo method. This novel technique
      deconvolves the incident pulse from the reflected pulse, and uses the resulting
      impulse response to produce an image of the acoustic impedance distribution. It
      is applicable mainly to structures that resemble a layered medium. The images
      captured by this method prove to have improved resolution and are free of
      speckle. With this method one can use ultrasound of lower frequencies than would
      be required by the pulse-echo method to achieve the same resolution. To provide
      further improvement of images the second harmonic signals can be employed. Here
      we describe the deconvolved inverse scattering imaging technique with account of
      the second harmonic signal. For this purpose the hybrid transducer by Krautkramer
      Branson Co., which consists of a cylindrical 5 MHz transducer wrapped in an
      annulus-shaped 2.5 MHz transducer, has been used. The phantom and soft tissue
      were imaged and in both cases the account of the second harmonic reflection data
      provides an improvement of the image quality.

PMID- 14579865
TI  - Science and sports: a brief history of muscle, motion and ad hoc organizations.
AB  - Both the history of biolocomotion (later to become motion analysis/biomechanics)
      and of electrology (later kinesiological electromyography) are to be traced back
      to approximatively the same period in the second half of the seventeenth century.
      The major contributors to these emergent sciences were Swammerdam in 1658 and
      Borelli in 1680. Some 150 years later, electrophysiological methods were derived
      and motion-cinephotography was developed from their pioneering work.
      Subsequently, use was made of motion analysis by means of cinephotography,
      forming a basis for biomechanics. The work of Marey in 1873 in particular
      stimulated the multidisciplinary study of human activity, providing models for
      contemporary sports scientists working in applied settings. The link between
      theory and practice in motion sciences and the multidisciplinary model of Marey
      were the motive and the example for establishing the Working Group of
      Biomechanics in the 1960s. This body has gone through a series of progressive
      developments, culminating in the approval of the World Commission of Science and
      Sports as a service group of the International Council for Sport Science and
      Physical Education (recognized by UNESCO).

PMID- 14579866
TI  - Biomechanical aspects of new techniques in alpine skiing and ski-jumping.
AB  - There have been considerable changes in equipment design and movement patterns in
      the past few years both in alpine skiing and ski-jumping. These developments have
      been matched by methods of analysing movements in field conditions. They have
      yielded new insights into the skills of these specific winter sports. Analytical
      techniques have included electromyography, kinetic and kinematic methods and
      computer simulations. Our aim here is to review biomechanical research in alpine
      skiing and ski-jumping. We present in detail the techniques currently used in
      alpine skiing (carving technique) and ski-jumping (V-technique), primarily using
      data from the authors' own research. Finally, we present a summary of the most
      important results in biomechanical research both in alpine skiing and ski
      jumping. This includes an analysis of specific conditions in alpine skiing (type
      of turn, terrain, snow, speed, etc.) and the effects of equipment, materials and
      individual-specific abilities on performance, safety and joint loading in ski
      jumping.

PMID- 14579867
TI  - Science and football: a review of applied research in the football codes.
AB  - Over the last two decades there has been a growth in research directly related to
      football. Although most of this research is focused on soccer (association
      football), there has been a steady increase in publications related to the other
      football codes. There is evidence of more systematic training and selection
      influencing the anthropometric profiles of players who compete at the highest
      level. Fitness is being optimized to cope with match demands while accommodating
      the need for specific requirements of positional roles. There is evidence of work
      rate being higher in contemporary football games than in previous decades, with
      consequences for training and dietary practices. Notation analysis of actions
      during matches is now used regularly to provide detailed objective feedback on
      performance to players and coaches. Training regimens are designed for game
      specific purposes where possible. Sports psychologists working in a football
      context have a more eclectic body of knowledge to draw from. In the professional
      soccer clubs, the rewards associated with a successful investment in youth
      academies have helped to focus attention on talent identification and development
      models. It is a challenge to those specializing in science and football to
      contribute to the success of such schemes.

PMID- 14579868
TI  - Science and the major racket sports: a review.
AB  - The major racket sports include badminton, squash, table tennis and tennis. The
      growth of sports science and the commercialization of racket sports in recent
      years have focused attention on improved performance and this has led to a more
      detailed study and understanding of all aspects of racket sports. The aim here,
      therefore, is to review recent developments of the application of science to
      racket sports. The scientific disciplines of sports physiology and nutrition,
      notational analysis, sports biomechanics, sports medicine, sports engineering,
      sports psychology and motor skills are briefly considered in turn. It is evident
      from these reviews that a great deal of scientific endeavour has been applied to
      racket sports, but this is variable across both the racket sports and the
      scientific disciplines. A scientific approach has helped to: implement training
      programmes to improve players' fitness; guide players in nutritional and
      psychological preparation for play; inform players of the strategy and tactics
      used by themselves and their opponents; provide insight into the technical
      performance of skills; understand the effect of equipment on play; and accelerate
      the recovery from racket-arm injuries. Racket sports have also posed a unique
      challenge to scientists and have provided vehicles for developing scientific
      methodology. Racket sports provide a good model for investigating the interplay
      between aerobic and anaerobic metabolism and the effect of nutrition, heat and
      fatigue on performance. They have driven the development of mathematical
      solutions for multi-segment interactions within the racket arm during the
      performance of shots, which have contributed to our understanding of the
      mechanisms of both performance and injury. They have provided a unique challenge
      to sports engineers in relation to equipment performance and interaction with the
      player. Racket sports have encouraged developments in notational analysis both in
      terms of analytical procedures and the conceptualization of strategy and tactics.
      Racket sports have provided a vehicle for investigating fast interceptive
      actions, hand-eye coordination and perception-action coupling in the field of
      motor control. In conclusion, science has contributed considerably to our
      knowledge and understanding of racket sports, and racket sports have contributed
      to science by providing unique challenges to researchers.

PMID- 14579869
TI  - The science and medicine of cricket: an overview and update.
AB  - Research into the science and medicine underlying cricket performance and injury
      has progressed since the First World Congress of Science and Medicine in Cricket
      in 1999. This review covers material on the physiological and psychological
      demands of the game and preparation for it, the biomechanics and motor control of
      cricket skills, the psychology of team dynamics, performance analysis and cricket
      injuries. Technological aspects of cricket equipment are also covered, where such
      research could influence injury risk or player performance. Fielding remains the
      least studied of the skills. Much more research needs to be done before we can
      gain a full understanding of the scientific aspects of the game. There is a need
      to address common definitions of injury, along with more research into injury
      mechanisms. Research on batting needs to bring together motor control and
      biomechanics more fully. The fitness demands of the game are still poorly
      understood, along with the mechanisms causing fatigue. Evaluation of the efficacy
      of intervention strategies needs to continue and to develop. The applications of
      research need to be communicated more to coaches and players--for example, in
      team dynamics--so that they can be applied, and tested further, in international
      matches.

PMID- 14579871
TI  - Science and cycling: current knowledge and future directions for research.
AB  - In this holistic review of cycling science, the objectives are: (1) to identify
      the various human and environmental factors that influence cycling power output
      and velocity; (2) to discuss, with the aid of a schematic model, the often
      complex interrelationships between these factors; and (3) to suggest future
      directions for research to help clarify how cycling performance can be optimized,
      given different race disciplines, environments and riders. Most successful
      cyclists, irrespective of the race discipline, have a high maximal aerobic power
      output measured from an incremental test, and an ability to work at relatively
      high power outputs for long periods. The relationship between these
      characteristics and inherent physiological factors such as muscle
      capilliarization and muscle fibre type is complicated by inter-individual
      differences in selecting cadence for different race conditions. More research is
      needed on high-class professional riders, since they probably represent the
      pinnacle of natural selection for, and physiological adaptation to, endurance
      exercise. Recent advances in mathematical modelling and bicycle-mounted strain
      gauges, which can measure power directly in races, are starting to help unravel
      the interrelationships between the various resistive forces on the bicycle (e.g.
      air and rolling resistance, gravity). Interventions on rider position to optimize
      aerodynamics should also consider the impact on power output of the rider. All
      terrain bicycle (ATB) racing is a neglected discipline in terms of the
      characterization of power outputs in race conditions and the modelling of the
      effects of the different design of bicycle frame and components on the magnitude
      of resistive forces. A direct application of mathematical models of cycling
      velocity has been in identifying optimal pacing strategies for different race
      conditions. Such data should, nevertheless, be considered alongside physiological
      optimization of power output in a race. An even distribution of power output is
      both physiologically and biophysically optimal for longer ( > 4 km) time-trials
      held in conditions of unvarying wind and gradient. For shorter races (e.g. a 1 km
      time-trial), an 'all out' effort from the start is advised to 'save' time during
      the initial phase that contributes most to total race time and to optimize the
      contribution of kinetic energy to race velocity. From a biophysical standpoint,
      the optimum pacing strategy for road time-trials may involve increasing power in
      headwinds and uphill sections and decreasing power in tailwinds and when
      travelling downhill. More research, using models and direct power measurement, is
      needed to elucidate fully how much such a pacing strategy might save time in a
      real race and how much a variable power output can be tolerated by a rider. The
      cyclist's diet is a multifactorial issue in itself and many researchers have
      tried to examine aspects of cycling nutrition (e.g. timing, amount, composition)
      in isolation. Only recently have researchers attempted to analyse
      interrelationships between dietary factors (e.g. the link between pre-race and in
      race dietary effects on performance). The thermal environment is a mediating
      factor in choice of diet, since there may be competing interests of replacing
      lost fluid and depleted glycogen during and after a race. Given the prevalence of
      stage racing in professional cycling, more research into the influence of
      nutrition on repeated bouts of exercise performance and training is required.

PMID- 14579870
TI  - Golf science research at the beginning of the twenty-first century.
AB  - At the beginning of the twenty-first century, there are 30,000 golf courses and
      55 million people who play golf worldwide. In the USA alone, the value of golf
      club memberships sold in the 1990s was US dollar 3.2 billion. Underpinning this
      significant human activity is a wide variety of people researching and applying
      science to sustain and develop the game. The 11 golf science disciplines
      recognized by the World Scientific Congress of Golf have reported 311 papers at
      four world congresses since 1990. Additionally, scientific papers have been
      published in discipline-specific peer-reviewed journals, research has been
      sponsored by the two governing bodies of golf, the Royal and Ancient Golf Club of
      St. Andrews and the United States Golf Association, and confidential research is
      undertaken by commercial companies, especially equipment manufacturers. This
      paper reviews much of this human endeavour and points the way forward for future
      research into golf.

PMID- 14579872
TI  - Anticaries efficacy of a new dentifrice for hypersensitivity.
AB  - PURPOSE: To evaluate the expected anticaries efficacy of a new dentifrice
      containing stannous fluoride as the anticaries agent and potassium nitrate as the
      antihypersensitivity agent using a series of laboratory and animal studies.
      METHODS: Four surrogate studies were performed in this assessment including
      fluoride uptake in sound enamel, enamel solubility reduction, fluoride
      bioavailability and animal caries. RESULTS: Each of these studies indicated the
      new dentifrice for hypersensitivity (Colgate Sensitive Maximum Strength) was
      effective in inhibiting the caries process. The data demonstrate that this new
      dentifrice is predicted to be highly effective against caries and equivalent to a
      positive control dentifrice.

PMID- 14579873
TI  - Plaque removal efficacy of a prototype power toothbrush compared to a positive
      control manual toothbrush.
AB  - PURPOSE: Recently, a new experimental battery-powered toothbrush was developed as
      a second generation to Crest SpinBrush. The brush head of this new prototype
      toothbrush (Crest SpinBrush Pro) incorporates a dual moving head design with one
      oscillating and the other translating back and forth. The objective of this study
      was to compare the plaque removal efficacy of a positive control manual
      toothbrush (Oral-B Cross Action) to this prototype power toothbrush following a
      repeated single use study design. In addition, this paper reports the results of
      a study examining the relative plaque removal efficacy of the positive control
      manual toothbrush to seven representative manual toothbrushes. METHODS: This
      study was a randomized, controlled, examiner-blind, four-period crossover design,
      which examined plaque removal with the two toothbrushes following a single use in
      40 subjects. Plaque was scored before and after brushing using the Turesky
      Modification of the Quigley-Hein Index. RESULTS: Baseline plaque scores were 2.61
      and 2.66 for the prototype power toothbrush and control toothbrush treatment
      groups, respectively. With respect to all surfaces examined, the prototype power
      toothbrush delivered an adjusted (via analysis of covariance) mean difference
      between baseline and post-brushing plaque scores of 0.98 while the control
      toothbrush delivered an adjusted mean difference of 0.74. The experimental
      toothbrush group, on average, had a 32.8% larger plaque removal score than the
      control toothbrush. These results were statistically significant (P < 0.001).
      Similar results were observed on buccal and lingual surfaces. In addition,
      results from the study comparing manual toothbrushes showed that the positive
      control manual toothbrush had higher plaque removal scores compared to seven
      representative manual toothbrushes. The plaque removal score differences reached
      statistical significance for five of the seven toothbrushes.

PMID- 14579874
TI  - In vitro validation of carious dentin removed using different excavation
      criteria.
AB  - PURPOSE: To compare directly the extent of cavity preparation instigated by
      either clinical hardness or a caries detector dye. Caries removal was
      histologically validated against the autofluorescence of carious dentin within
      the same samples. METHODS: 50 human molars were sectioned longitudinally through
      occlusal lesions, color photomicrographs obtained and the pre-excavation
      autofluorescent signatures captured using a confocal laser scanning microscope
      (488 nm excitation, > 515 nm emission). The hydrated lesions were excavated using
      sterile hand instruments until the dentin cavity surface was hard to a dental
      probe. Color photomicrographs were obtained and then caries detector dye was then
      placed in the cavities and excavation continued until no pink stain was visible.
      Final color photomicrographs were obtained. RESULTS: Digital image
      superimpositions indicated that the extent of cavities prepared using the
      clinical hardness criterion correlated closely to the corresponding
      autofluorescent signal outlines of the original lesions. Caries detector dye
      assisted excavation resulted in over-prepared cavities by as much as 58.2%
      relative to the validating autofluorescence outline. In conclusion, the use of
      caries dyes can lead to clinically significant over-preparation of cavities when
      compared to those prepared using clinical hardness.

PMID- 14579875
TI  - Effect of welding method on joint strength of laser-welded gold alloy.
AB  - PURPOSE: To examine the effect of welding method and heat treatment on the
      strength of laser-welded gold alloy with age-hardenability at intraoral
      temperature. METHODS: Cast gold alloy plates (0.5 x 3.0 x 20 mm3) were prepared
      and cut perpendicular to the 3.0 mm surface of the plate. After the cut halves
      were fixed in a jig, they were laser-welded using a Nd: YAG laser. Three laser
      pulses were applied from one side (single-welded) or both sides (double-welded)
      to weld the entire joint width of the specimens. Three different heat treatments
      were given the specimens: solution treatment at 700 degrees C for 5 minute (ST),
      aging at 250 degrees C for 15 minute after ST (HA), and aging at 37 degrees C for
      3 day after ST (IA). As-cast specimens were also reserved. Uncut specimens served
      as non-welded control specimens. Tensile testing was conducted at a crosshead
      speed of 2 mm/minute and a gauge length of 10 mm. The breaking stress (Bs: MPa)
      was recorded, and the data (n = 5 per group) were statistically analyzed.
      RESULTS: In the control groups, the Bs values of the IA were not significantly
      different (P > 0.05) from those of the HA specimens. The laser-welded IA
      specimens showed significantly greater (P < 0.05) Bs values compared to the
      solution-treated and as-cast specimens. The double-welded specimens showed
      significantly greater Bs values compared to the single-welded specimens after any
      heat treatment.

PMID- 14579876
TI  - Compatibility of dental adhesives and dual-cure cements.
AB  - PURPOSE: To evaluate the extrusion shear strength of bonding between porcelain
      and dentin. METHODS: The adhesives tested were Prime&Bond NT in both dual-cure
      and light-cure versions, Scotchbond Multi-Purpose Plus, One-Step and Single Bond.
      The cements evaluated were RelyX ARC and Enforce. Discs of bovine root dentin 2.5
      mm thick had the canal prepared with a standardized taper. Porcelain truncated
      cones were bonded into the perforations. Cements were tested in dual-cure and
      self-cure mode. Extrusion shear strength test was performed after 48 hours
      storage in 37 degrees C distilled water. Data were analyzed by three-way
      ANOVA/Tukey's test. RESULTS: Bond strength values ranged from 5.5 MPa to 8.9 MPa
      when cements were tested in dual-cure mode, and from 1.4 MPa to 6.9 MPa when
      tested in self-cure mode. Scotchbond Multi-Purpose Plus was the only adhesive to
      present similar results when associated with cements in dual-cure and self-cure
      modes. For the other adhesives, differences in bond strength from 33 to 76% were
      observed between dual-cure and self-cure modes.

PMID- 14579877
TI  - Relationship between composite contraction stress and leakage in Class V
      cavities.
AB  - PURPOSE: The purpose of this study was to determine the relationship between
      polymerization contraction stress and leakage in Class V composites. METHODS: A
      microfill (Heliomolar) and two minifill hybrid composites (Herculite, Z100) were
      tested. Maximum contraction stress (n = 5) for the composites was evaluated in a
      MTS machine at a C-factor of 3 (ratio of bonded to non-bonded surface area).
      Composite was placed in the gap between the surfaces of glass stubs that had been
      air abraded, silane treated and coated with a layer of resin adhesive. Specimens
      were light-cured through the top glass stub for 60 seconds and maximum force was
      recorded during the first 10 minutes. Leakage (n = 10) was evaluated by cutting
      cylindrical cavity preparations with all enamel margins (C-factor = 3) in bovine
      incisors. The cavities were treated with two layers of Scotchbond MP adhesive.
      Composites were applied in one increment, light-cured at the same intensity used
      in the stress tests, and immediately finished on SiC paper. After 1 day in water,
      the restorations were placed in silver nitrate, developed and evaluated as a
      single cross-section (2-D) and multiple cross-sections (3-D) for leakage: 0
      (none), 1 (minimal leakage), 2 (to the DEJ), 3 (to line angle), 4 (along the
      pulpal wall). RESULTS: The maximum stresses (MPa) recorded were lowest for
      Heliomolar (7.0 +/- 0.4), intermediate for Herculite (10.5 +/- 0.6) and greatest
      for Z100 (11.6 +/- 1.3). 3-D leakage was as follows: Heliomolar--two specimens
      scored 1, seven scored 2 and one scored 3; Herculite--six scored 2 and four
      scored 3; Z100--eight scored 3 and two scored 4. The Kruskal-Wallis test showed a
      significant difference in leakage for the three composites (P < 0.05), and
      leakage was greater when evaluated in 3-D. The leakage results correlated with
      the stress values, i.e. composites with higher contraction stress showed more
      extensive marginal leakage.

PMID- 14579878
TI  - Effect of low-viscosity resin-based composite on the microleakage of cervical
      restorations.
AB  - PURPOSE: To investigate the effect of a low-viscosity resin-based composite (LVC)
      liner on the microleakage of cervical resin-based composites bonded with new
      adhesive systems. METHODS: 180 wedge-shaped cervical cavities on bovine incisors
      were treated with AQ Bond (all-in-one), ABF (experimental two-step self-etching
      primer containing antibacterial monomer) or Clearfil SE Bond (two-step self
      etching primer) systems according to the manufacturers' instructions. Half of the
      treated cavities in each adhesive system were lined with an LVC (Protect Liner F)
      and filled with a hybrid resin-based composite (Clearfil AP-X). Ten specimens
      from each group were immersed in 0.5% basic fuchsin solution immediately after
      finishing the restorations. The specimens to be subjected to thermocycling (5-60
      degrees C, 15 seconds dwell time, 5,000 cycles) or to flexural load cycling
      (approximately 0.5 mm labio-lingual displacement at the incisal edge, 10,000
      cycles, 1 Hz) prior to immersion in the dye solution were also prepared. The
      teeth were sectioned through the center of the restorations and the degrees of
      dye penetration were scored. The data were analyzed with the Mann-Whitney U-test
      or the Kruskal-Wallis test (P < 0.05). RESULTS: The use of the LVC liner
      significantly improved marginal sealing of AQ Bond. However, the LVC liner could
      not prevent the deterioration in the marginal integrity caused by thermocycling
      or flexural load cycling. In the case of ABF, the use of the LVC liner showed a
      trend toward less microleakage. For Clearfil SE Bond, the LVC liner prevented the
      deterioration in the marginal seal caused by thermocycling.

PMID- 14579879
TI  - Clinical trial of a self-etching adhesive for sealant application: success at 24
      months with Prompt L-Pop.
AB  - PURPOSE: To evaluate the 2-year clinical sealant success when using Prompt L-Pop
      (3M-ESPE), the first self-etching adhesive, as the sole etching and adhesive step
      prior to sealant placement. METHODS: Patients ages 7-13 years with matched pairs
      of permanent molars needing sealants were enrolled into an ongoing clinical study
      of sealant success. First and/or second permanent molars were randomly assigned
      to control (sealant only after phosphoric acid etch) or Prompt plus sealant
      groups in a split-mouth, matched pair study design. Standard methods were used
      for sealant (Delton, Dentsply) placement, except for the Prompt group in which
      the self-etching adhesive was brushed on the surface, air thinned, followed by
      immediate placement of the sealant and polymerization. All sealants were placed
      using appropriate cotton-roll isolation and a dental assistant. Sealant scoring
      was done at 24 months using strict clinical criteria for failure, previously
      published, and photos of the sealed surfaces were archived on video. RESULTS:
      Percentages of sealants scored as successful (no significant loss of material or
      need for repair) through 24 months were: (a) Occlusal sealants: Control = 61%,
      versus Prompt = 61%; (b) Bu/Lingual sealants: Control = 54%, versus Prompt = 62%;
      McNemar's Chi Square tests indicate no difference in success between the Prompt
      sealants and their matched controls (P > 0.80). Time of placement for sealants,
      timed from start of the etch step through polymerization, averaged 3.1 minutes
      for Control and 1.8 minutes for Prompt. We conclude that Prompt L-Pop self
      etching adhesive is effective in bonding sealant to enamel and that the
      simplified method dramatically shortens treatment time and treatment complexity.

PMID- 14579880
TI  - Shear bond strengths of composite bonded to porcelain using porcelain repair
      systems.
AB  - PURPOSE: To measure and compare the shear bond strengths to porcelain of two
      composites used with each of two different porcelain bonding systems. METHODS: 40
      porcelain specimens were mounted in acrylic resin, ground flat using 120 and 320
      grit sandpaper, and randomly divided into four groups of 10 for specimen
      fabrication as follows: Group 1: Premier MicroDose Porcelain Bonding/Optibond FL
      adhesive/Prodigy composite; Group 2: Premier MicroDose Porcelain Bonding/PQ1
      adhesive/Amelogen composite; Group 3: Ultradent Porcelain Etch/Optibond FL
      adhesive/Prodigy composite; Group 4: Ultradent Porcelain Etch/PQ1
      adhesive/Amelogen composite. Manufacturers' directions were followed to treat the
      porcelain surface and apply the adhesive and composite to each specimen.
      Following storage in distilled water at 37 degrees C for 7 days, the specimens
      were subjected to shear testing using an MTS 858 Universal Testing Machine. Data
      were recorded and analyzed using a one-way ANOVA and t-test. RESULTS: There was
      no significant difference in mean shear bond strength among the four groups (P =
      0.575) or between the two groups with the highest and lowest mean shear bond
      strength (P = 0.288). The mean shear bond strength for all groups exceeded 21 MPa
      and 39 of 40 specimens exhibited cohesive fracture in porcelain.

PMID- 14579881
TI  - Three-year clinical performance of a compomer in stress-bearing restorations in
      permanent posterior teeth.
AB  - PURPOSE: To evaluate the 3-year clinical performance of the compomer Hytac in
      Class I and II cavities of permanent posterior teeth. METHODS: 53 restorations
      were placed in 14 patients. The compomer Hytac was used with the self-etching
      adhesive Hytac OSB (total bonding) without additional enamel-etching with
      phosphoric acid according to manufacturer's instructions. Restorations were rated
      at baseline and 3 years according to modified USPHS criteria in relation to tooth
      type (molar, premolar), size and class of cavities, isolation type (rubber dam,
      cotton rolls) and use of a calcium hydroxide liner. After 3 years, 39
      restorations (73.6%) were available for examination. Statistical analysis was
      performed using Mann-Whitney U test and Fisher's exact test. RESULTS: After 3
      years, three restorations failed (7.7%). The success rate was therefore 92.3%
      with an average annual failure rate of 2.6%. There was no statistically
      significant difference (P < 0.05) found concerning neither of the USPHS criteria
      nor the failures between any of the restoration groups.

PMID- 14579882
TI  - Indoor environment quality in dental clinics: potential concerns from particulate
      matter.
AB  - PURPOSE: To provide a comprehensive assessment of the indoor environment of a
      representative dental office. METHODS: Health and comfort parameters, including
      carbon dioxide (CO2), respirable particulate matter (PM2.5), volatile organic
      compounds (VOCs), temperature, relative humidity, light and sound level, were
      measured at three sites over a 1-week period. Both real-time and integrated
      sampling methods were used, and clinic activities were recorded. Measurements
      were compared to guidelines and standards, and interactions between pollutant
      levels, emissions, and clinic activities were investigated using correlations,
      trend analyses, and a ventilation assessment. RESULTS: Comfort parameters were
      found to be within recommended values, with the exception of relative humidity,
      which was low but not unusual for the winter season investigated. Ventilation
      rates were within accepted guidelines. Integrated sampling showed that
      concentrations of VOCs were well below guidelines. However, PM2.5 levels exceeded
      ambient standards (by a factor of 2 to 6) throughout the building. Continuous
      trending allowed identification of peak levels, but correlations of clinic
      activities with measured concentrations were inconclusive. The results suggested
      that levels of air contaminants in dental clinics (with the exception of PM) are
      within guideline levels. With the recirculating ventilation systems found in most
      clinics and offices, particulate contaminants may rapidly disperse throughout a
      building. Improved capture, exhaust and filtration would decrease indoor PM
      concentrations. If contaminants are pathologic, the ramifications for
      practitioners may be considerable, and some specialists may be particularly at
      risk.

PMID- 14579883
TI  - Morphological study of resin-dentin bonding with TEM and in-lens FESEM.
AB  - PURPOSE: To evaluate the morphological characteristics of the dentin-resin
      interface using high-magnification electron microscopy and correlate the TEM
      findings of resin-dentin interfaces with the corresponding in-lens Field Emission
      SEM (FEISEM) observation. METHODS: Twelve 800 microm-thick dentin disks were
      obtained from middle dentin and assigned to four groups: (1) a self-etching
      adhesive material, Clearfil SE Bond; (2) a solvent-free total-etch simplified
      adhesive, One Coat Bond; (3) an acetone-based total-etch simplified adhesive,
      Prime&Bond NT; (4) an acetone-based total-etch simplified adhesive, Prime&Bond
      NT, upon a short dentin deproteinization with 10% NaOCl gel (AD Gel) for 15
      seconds. Disks were restored with a 1 mm thick layer of a low-viscosity
      composite. Four sticks with a cross section of 1 mm2 were taken from each
      restored dentin disk, decalcified in buffered 10% EDTA, fixed, and stained with
      lead citrate followed by uranyl acetate, or kept in water. The sticks were
      sectioned in 85 nm-thick slices, and mounted on Ni grids. After TEM observation,
      the same grids were coated with a 1.5 nm Pt-C film and observed under the FEISEM.
      RESULTS: The TEM analysis revealed an intimate adaptation of all adhesive systems
      to dentin, with penetrating resin tags observed in transverse sections. The
      FEISEM revealed novel morphological features usually observed in the resin-dentin
      interface with distinctive arrangement for each of the adhesive systems. FEISEM
      and TEM appear as mutually complementary tools for the fine observation of the
      ultra-structure and the spatial relationship between the resin components and the
      collagen fibers of the hybrid layer.

PMID- 14579884
TI  - Potential of restorative systems with simplified adhesives: quantitative analysis
      of wear and marginal adaptation in vitro.
AB  - PURPOSE: This in vitro study evaluated: (1) marginal adaptation and (2)
      attritional wear of composite resin materials with simplified bonding systems.
      METHODS: 36 standardized Class II MOD cavities were prepared in human mandibulary
      first molars and divided randomly in six equal groups. Restorations were placed
      with combinations of resin composites and simplified bonding systems: A = Arabesk
      and Solobond, B = Z 100 and Scotchbond 1, C = Prodigy and OptiBond, D = FHC Merz
      light and Resulcin Aqua Prime/Monobond as well as E = Sculpt-It and Bond 1. F =
      Amelogen Universal in combination with the classical 3 part adhesive system
      Permaquick served as control for marginal adaptation. For wear rates, enamel
      versus human enamel served as control. All specimens were subjected to long-term
      thermomechanical stress in a computer-controlled masticator. Human enamel cusps
      served as antagonists. Marginal adaptation was evaluated by SEM quantitatively
      before and after stress. Attritional wear in occlusal contact areas was measured
      on specimens and antagonists with a surface analyzer. Results were tested for
      statistical significance with ANOVA. RESULTS: SEM marginal analysis exhibited
      variations from 45.1 +/- 19.9% (D) to 7.9 +/- 5.4% (E) continuous margin after
      thermomechanical loading in test groups. All groups achieved statistically
      significant lower scores (P < 0.05) for marginal adaptation than the control (F:
      87.4 +/- 15.5%). Total attritional wear (specimen + antagonist) varied from 153.2
      +/- 32.3 microm (D) to 272.3 +/- 132.7 microm (A). Wear of A and F was
      statistically significantly higher (P < 0.05) than enamel versus enamel (162.2 +/
      111.2 microm).

PMID- 14579885
TI  - Basic practice management systems. Part II of the dental management pyramid
      series.
AB  - Mastering basic management systems is the first of six levels in the Dental
      Management Pyramid that determines the future direction of your practice. It is
      important to avoid the temptation to move from one level to the next until you
      have addressed all aspects of the current level. All too often, dentists attempt
      to move up the pyramid without completing each level, leaving incomplete
      management in other areas. Business systems allow for the highest level of
      profitability, the lowest stress, and the most enjoyment for you and your team
      members. They serve as the very foundation on which you build your successful
      dental practice. In the next installment of this series, leadership skills and
      team development will be discussed.

PMID- 14579886
TI  - Methodology issues in epidemiological assessment of health effects of low-dose
      ionising radiation.
AB  - Epidemiological assessment of the health effects of exposure to low-dose ionising
      radiation is limited by the need for very large sample sizes and by various
      sources of bias that may generally affect epidemiological studies. Motivated by
      the present focus on low-dose effects, the following questions are examined: what
      are the strictly unavoidable limiting factors in the epidemiological methodology;
      what is its resolution limit in terms of effect size and what can be done to
      obtain further supportive evidence from the data?

PMID- 14579887
TI  - Studies of radon and lung cancer in North America and China.
AB  - Studies of radon-exposed underground miners indicate that residential radon is
      the second leading cause of lung cancer. Seven case-control studies of
      residential radon have been conducted in North America and two in China, and
      represent all studies in these areas which included 200 or more lung cancer cases
      and used long-term radon detectors. North American studies enrolled 4081 cases
      and 5281 controls, and Chinese studies enrolled 1076 cases and 2015 controls.
      Based on analyses of pooled data, odds ratios (ORs) and 95% confidence limits at
      100 Bq m(-3) were 1.106 (1.00,1.28) for the North American studies and 1.139
      (1.01,1.37) for the Chinese studies. Tests of homogeneity of ORs within
      populations were not significant. Among subjects with complete dosimetry for the
      5-30 y exposure period prior to interview, ORs at 100 Bq m(-3) were 1.205
      (1.03,1.50) for the North American studies and 1.279 (1.07,0.75) for the Chinese
      studies. Results are consistent with extrapolations from miners and indicate an
      excess lung cancer risk from residential radon.

PMID- 14579888
TI  - Health effects of residential radon: a European perspective at the end of 2002.
AB  - Surveys of indoor radon concentrations, when taken together with estimates of the
      risk of lung cancer from studies in miners of uranium and other hard rocks,
      suggest that residential radon is responsible for many thousands of deaths from
      lung cancer each year in Europe. The vast majority of these deaths are likely to
      occur in individuals who also smoke cigarettes. Because of the skewed nature of
      the distribution of the indoor radon concentrations in most populations, most of
      the deaths will occur in individuals who are exposed at moderate rather than at
      very high radon concentrations. In order to enable appropriate policies to be
      developed for managing the consequences of exposure to radon, more reliable
      estimates of the risk of lung cancer resulting from it are needed. To achieve
      this, a European Collaborative Group on Residential Radon and Lung Cancer was
      initiated and its findings should be published in 2004.

PMID- 14579889
TI  - Studies on the Hiroshima and Nagasaki survivors, and their use in estimating
      radiation risks.
AB  - Epidemiological studies of the survivors of the atomic bombings of Hiroshima and
      Nagasaki have been conducted over many years. These studies have examined, inter
      alia, mortality and cancer incidence among the survivors. This paper summarises
      the form of the studies undertaken, outlines the main findings and describes how
      these results can be used in deriving estimates of radiation risks. In doing so,
      some areas of uncertainty and open issues are highlighted, such as the magnitude
      of lifetime cancer risks and the evidence for raised risks of non-cancer diseases
      at low doses. Continued follow-up of the survivors will be important in shedding
      further light on these issues.

PMID- 14579890
TI  - Relative implications of protective responses versus damage induction at low dose
      and low-dose-rate exposures, using the microdose approach.
AB  - In reviewing the tissue effects of low-dose radiation (1) absorbed dose to tissue
      is replaced by the sum of energy deposited with track events in cell-equivalent
      tissue micromasses, i.e. with microdose hits, in the number of exposed
      micromasses and (2) induced cell damage and adaptive protection are related to
      microdose hits in exposed micromasses for a given radiation quality. DNA damage
      increases with the number of microdose hits. They also can induce adaptive
      protection, mainly against endogenous DNA damage. This protection involves
      cellular defences, DNA repair and damage removal. With increasing numbers of low
      linear energy transfer (LET) microdose hits in exposed micromasses, adaptive
      protection first tends to outweigh damage and then (above 200 mGy) fails and
      largely disappears. These experimental data predict that cancer risk coefficients
      derived by epidemiology at high-dose irradiation decline at low doses and dose
      rates when adaptive protection outdoes DNA damage. The dose-risk function should
      include both linear and non-linear terms at low doses.

PMID- 14579891
TI  - A review of the bystander effect and its implications for low-dose exposure.
AB  - Current models for the interaction between ionising radiation and living cells or
      tissues are based on direct genetic damage produced by energy deposition in
      cellular DNA. An important observation which has questioned this basic assumption
      is the radiation-induced bystander response, in which cells which have not been
      directly targeted respond if their neighbours have been exposed. This response
      predominates at low doses of relevance to radiation risk analysis (<0.2 Gy) and
      therefore needs to be fully characterised. The development of microbeams, which
      allow individual cells within populations to be targeted with precise doses of
      radiation, has provided a useful tool for quantifying this response. The authors'
      studies have targeted individual human and mouse cells with counted protons and
      helium ions and monitored neighbouring cells for the production of bystander
      responses. Bystander responses have been measured after exposures as low as a
      single proton or helium ion delivered to an individual cell. An important aspect
      is that these responses saturate with increasing dose to the single target cell,
      thus the relative roles of direct and indirect (non-targeted) responses change
      with dose. Studies with multicellular, tissue-based models are providing evidence
      that bystander responses may have a complex phenotype involving multiple pathways
      and the overall response may be a balance between multiple signalling processes
      and responses to radiation exposure. Current models for radiation risk assume a
      linear non-threshold response and have generally been extrapolated from high-dose
      exposures. The involvement of competing processes at low doses may have important
      consequences for understanding the effects of low-dose exposure.

PMID- 14579892
TI  - Biological parameters for lung cancer in mathematical models of carcinogenesis.
AB  - Applications of the two-step model of carcinogenesis with clonal expansion (TSCE)
      to lung cancer data are reviewed, including those on atomic bomb survivors from
      Hiroshima and Nagasaki. British doctors, Colorado Plateau miners and Chinese tin
      miners. Different sets of identifiable model parameters are used in the
      literature. The parameter set which could be determined with the lowest
      uncertainty consists of the net proliferation rate gamma of intermediate cells,
      the hazard h55 at an intermediate age and the hazard h(infinity) at an
      asymptotically large age. Also, the values of these three parameters obtained in
      the various studies are more consistent than other identifiable combinations of
      the biological parameters. Based on representative results for these three
      parameters, implications for the biological parameters in the TSCE model are
      derived.

PMID- 14579893
TI  - The use of biologically based cancer risk models in radiation epidemiology.
AB  - Biologically based risk projection models for radiation carcinogenesis seek to
      describe the fundamental biological processes involved in neoplastic
      transformation of somatic cells into malignant cancer cells. A validated
      biologically based model, whose parameters have a direct biological
      interpretation, can also be used to extrapolate cancer risks to different
      exposure conditions with some confidence. In this article biologically based
      models for radiation carcinogenesis, including the two-stage clonal expansion
      (TSCE) model and its extensions, are reviewed. The biological and mathematical
      bases for such models are described, and the implications of key model parameters
      for cancer risk assessment examined. Specific applications of versions of the
      TSCE model to important epidemiological datasets are discussed, including the
      Colorado uranium miners' cohort; a cohort of Chinese tin miners; the lifespan
      cohort of atomic bomb survivors in Hiroshima and Nagasaki; and a cohort of over
      200,000 workers included in the National Dose Registry (NDR) of Canada.

PMID- 14579894
TI  - Follow-up after cervical laminectomy, with special reference to instability and
      deformity.
AB  - Misalignment and instability after cervical laminectomy, performed to treat
      spondylotic myelopathy, has been described as possible adverse effects. Forty-six
      consecutively patients on whom laminectomy had been performed in a 4-year period
      were identified; 7.7 +/- 0.6 years after operation, 11 patients had died and 27
      patients were available for follow-up. Postoperative static subluxation was
      observed in 26% of the patients with an average slip of 3.7 +/- 3.1 mm; 7% had
      abnormal intervertebral movement displaying 1-2 mm movement from full flexion to
      full extension. Seventy-four per cent of the patients showed abnormal spinal
      curvature as judged from radiographs. However, no correlation with outcome was
      observed. Seventy-four per cent of the patients thought of the result of the
      operation as either good or fair; objectively, the best long-term effect of the
      operation was upon arm function. Although some patients develop postural anomaly,
      laminectomy remains, in terms of instability, a justifiable procedure in the
      elderly patient with spondylosis.

PMID- 14579895
TI  - Intermittent low dose intrathecal sodium nitroprusside therapy for treatment of
      symptomatic aneurysmal SAH-induced vasospasm.
AB  - Eight patients with aneurysmal subarachnoid haemorrhage (SAH) received
      intrathecal sodium nitroprusside therapy (ITSNPT) in the form of intermittent
      bolus doses for delayed cerebral vasospasm after undergoing clipping of an
      aneurysm. Five patients were administered ITSNPT to combat refractory symptomatic
      vasospasm while three patients received prophylactic ITSNPT in view of the
      possibility of imminent clinical vasospasm. In five patients the therapy was
      instituted through the intraventricular route, while in three the drug was
      instilled into the basal cistern. Sodium nitroprusside (SNP) was administered at
      an interval of 3-12 h, in varying bolus doses ranging between 2 and 5 mg
      depending upon the (i) mean flow velocity values on transcranial Doppler study
      and (ii) clinical response. The end point of ITSNPT was either relief of
      vasospasm, any adverse effect or contraindication to continuation of ITSNPT. All
      except one patient survived. One patient had mild residual neurological deficit
      following an infarct. All the three patients who received prophylactic ITSNPT had
      good outcomes.

PMID- 14579896
TI  - Continuous monitoring of intracranial compliance after severe head injury:
      relation to data quality, intracranial pressure and brain tissue PO2.
AB  - The objective of the present study was to test the new continuous intracranial
      compliance (cICC) device in terms of data quality, relationship to intracranial
      pressure (ICP) and brain tissue oxygenation (PtiO2). A total of 10 adult patients
      with severe traumatic brain injury underwent computerized monitoring of arterial
      blood pressure, ICP, cerebral perfusion pressure, end-tidal CO2, cICC and PtiO2
      providing a total of 1726 h of data. (1) The data quality assessed by calculating
      the 'time of good data quality' (TGDQ, %), i.e. the median duration of artefact
      free time as a percentage of total monitoring time reached 98 and 99% for ICP and
      PtiO2, while cICC measurements were free of artefacts in only 81%. (2) Individual
      regression analysis showed broad scattered correlation between cICC and ICP
      ranging from low (r = 0.05) to high (r = 0.52) correlation coefficients. (3) From
      225 episodes of increased ICP (ICP > 20 mmHg > 10 min), only 37 were correctly
      predicted by a preceding decline in cICC to pathological values (< 0.5 ml/mmHg).
      (4) In all episodes of cerebral hypoxia (PtiO2 < 10 mmHg > 10 min), cICC was not
      pathologically altered. Based on the present results, we conclude that the
      current hardware and software version of the cICC monitoring system is
      unsatisfactory concerning data quality, prediction of increased ICP and revelance
      of cerebral hypoxic episodes.

PMID- 14579897
TI  - Psychiatric, cognitive and behavioural outcomes following craniopharyngioma and
      pituitary adenoma surgery.
AB  - In order to determine the cognitive and behavioural changes in patients following
      craniopharyngioma surgery, all patients over the age of 16 years who had an
      operative intervention for craniopharyngioma between 1983 and 1998 were
      identified. Those consenting were interviewed using standardized instruments to
      assess for the presence of a psychiatric disorder, disturbance of behaviour or
      altered cognitive function. A control group of age- and sex-matched patients who
      had undergone pituitary adenoma excision were identically assessed. Eighteen
      people, of a total of 44, were interviewed. There were some differences in the
      subjective experience of appetite and the degree of control exercised over eating
      behaviour. Otherwise outcomes in cases and controls were similar. In the domains
      assessed, these two groups have similar outcomes from surgery.

PMID- 14579898
TI  - Natural history and clinical management of optic pathway glioma.
AB  - Twenty-five consecutive unselected patients with optic pathway glioma (OPG) were
      primarily observed and treated if progression was evident. Diagnosis was based on
      MRI. The natural history of the OPG disease was more indolent in 12 patients with
      neurofibromatosis 1 (NF1) than in the others, and regressions were commonly
      observed. Thirteen non-NF1 patients had larger rumours at diagnosis and more
      progressions. There were five intra-orbital optic nerve tumours (one with
      progression), 19 chiasmatic tumours (12 with progression) and one diffuse tumour.
      OPG emerges before the age of 7 years in NF1 patients, and in non-NF1 patients
      also in older patients including adults. Progressive intra-orbital OPGs are best
      treated by surgical resection. Progressive chiasmatic tumours are best treated by
      radiotherapy and respond well by marked regression. Exceptionally, exophytic
      chiasmatic tumours may be treated by chiasm preserving surgery.

PMID- 14579899
TI  - Delayed postoperative intracerebral abscess caused by Proprionibacterium acnes:
      case report and review of the literature.
AB  - A case of delayed intracerebral abscess due to Proprionibacterium acnes (P.
      acnes), 18 months after an uneventful excision of a parasagittal
      haemangiopericytoma in a 61-year-old female is reported. This is highly unusual
      as cerebral abscess by P. acnes is rare and it occurred so late postoperatively
      in the absence of known risk factors. We propose the inclusion of cerebral
      abscess by P. acnes in the differential diagnosis of lesions that mimic tumour
      recurrences, after clean craniotomies.

PMID- 14579901
TI  - Meningeal melanocytoma: clinical features and review of the literature.
AB  - A case of meningeal melanocytoma in the posterior fossa of a 16-year-old male is
      reported. Computed tomographic and magnetic resonance imaging features are
      presented. Pathological investigation including light and electron microscopy,
      and immunohistochemical staining are discussed. Current literature is reviewed
      and differentiating criteria from meningioma and other pigmented tumours of the
      nervous system are discussed.

PMID- 14579900
TI  - Metabolic changes during impending and manifest cerebral hypoxia in traumatic
      brain injury.
AB  - The objective was to measure metabolic changes monitored by bedside microdialysis
      during impending and manifest hypoxia in traumatic brain injury. In 41 patients,
      a PtiO2-catheter (Licox; 1/min) was placed into non-lesioned frontal white matter
      together with a microdialysis catheter (CMA, hourly). Data were analysed for
      identification of episodes of impending (PtiO2 < 10 - 15 mmHg > 5 min) and
      manifest cerebral hypoxia (PtiO2 < 10 mmHg, > 5 min). In 69% of patients hypoxic
      episodes occurred, most frequently associated with hyperventilation (p < 0.001).
      During impending hypoxia, glutamate was increased (p = 0.03), while the energy
      metabolites remained stable. Manifest hypoxia was reflected by significant
      increases of glutamate (p = 0.007) and lactate (p = 0.044), but normal lactate
      pyruvate ratios. We conclude that hyperventilation had a potential adverse effect
      on cerebral metabolism and was most frequently associated with cerebral hypoxia.
      A PtiO2 < 10 mmHg can induce metabolic changes with increase of glutamate and
      lactate. The presence of anaerobic cerebral metabolism probably depends on
      duration and severity of the hypoxic episode.

PMID- 14579902
TI  - Gliadel therapy given for first resection of malignant glioma: a single centre
      study of the potential use of Gliadel.
AB  - The results of a recently concluded phase III study have shown that Gliadel
      therapy (biodegradable polymer impregnated with 3.85% BCNU placed into the
      surgical cavity) significantly prolongs survival and time to relapse in patients
      having initial resective surgery for malignant glioma followed by radiotherapy.
      The indications and exclusion criteria for patients in this study were well
      defined. To determine the relative frequencies of Gliadel 'eligible' and
      'ineligible' patients, and differences in prognostic variables between these two
      cohorts, we conducted a review of all Edinburgh patients with an initial
      diagnosis of malignant glioma managed throughout the period of patient accrual
      into the phase III Gliadel study (Edinburgh was one of 38 contributing centres).
      Independent predictors of outcome were taken from the MRC prognostic index.
      Analysis was done on an intention to treat basis. Only 25% of patients (14/56)
      with malignant glioma managed over this period were eligible for the Gliadel
      study and all were recruited. The patients in the study group were younger
      (median 51 v. 59 years, p = 0.085); in better clinical grade (median Karnofsky
      score 85 v. 80, p = 0.038); more likely to have resective surgery (86% v. 38%, p
      = 0.0001); more likely to have postoperative radiotherapy (93% v. 55%, p =
      0.0001) and more likely to survive longer, even though one half of the Gliadel
      cohort received placebo, (66 v. 19 weeks, p = 0.06) than those not eligible. If
      the future use of Gliadel is limited to the eligibility criteria used in the
      phase III trial about 20% (95% confidence intervals 13-34%) of patients with
      newly diagnosed malignant glioma will receive this therapy.

PMID- 14579903
TI  - Terson's syndrome as the sole presentation of aneurysmal rupture.
AB  - The authors report a rare case of aneurysmal haemorrhage that presented with
      Terson's syndrome without any classical features of subarachnoid haemorrhage. The
      mechanism of this phenomenon is discussed and the importance of its
      identification is highlighted.

PMID- 14579904
TI  - Vertebral plasma cellular osteomyelitis.
AB  - Plasma cellular osteomyelitis is a chronic recurrent, unifocal or multifocal
      inflammatory disorder, which has an unknown aetiology. The infectious focus or
      foci may occur in different sites of the skeleton. This unusual clinical entity
      has been reported in over 200 cases in the relevant literature, but the
      involvement of the spine with plasma cellular osteomyelitis has not been reported
      before. Because of the rarity of this disease and the possible difficulty in
      differentiating plasma cell osteomyelitis, both clinically and
      histopathologically from the other similar afflictions of the spine, we describe
      our case.

PMID- 14579906
TI  - Anaplastic oligodendroglioma with metastasis to the spinal cord.
AB  - A case of intramedullary spinal metastasis presenting 14 months after excision of
      the primary anaplastic cerebral oligodendroglioma is presented. To the best of
      our knowledge, less than 10 cases of spinal metastasis have been reported in the
      world literature.

PMID- 14579905
TI  - Fibrosarcoma of the brachial plexus presenting in childhood.
AB  - We report a case of malignant fibrosarcoma involving the brachial plexus
      presenting in childhood. Primary malignant tumours of the brachial plexus are
      rare entities. In particular, fibrosarcoma of the brachial plexus occurring in a
      child has not been previously reported. Dilemmas in resolving the management and
      long-term consequences of this condition are discussed.

PMID- 14579907
TI  - Volume rendered MR angiography for the detection of small intracranial aneurysms.

PMID- 14579908
TI  - Transorbital penetrating craniocerebral injury by a spectacle arm: suicidal
      attempts.

PMID- 14579909
TI  - Temporal lobe seizures: unusual presentation of a giant unruptured posterior
      communicating artery aneurysm.

PMID- 14579910
TI  - Some concerns about the future of the practice of cardiovascular medicine.

PMID- 14579911
TI  - A case of global T-wave inversions and impaired left ventricular function
      following intense emotional distress.

PMID- 14579912
TI  - Oxidative stress and atheromatous plaques that are prone to rupture.

PMID- 14579913
TI  - Mending the broken heart.

PMID- 14579914
TI  - Rationale and design of the randomized, multicenter, cilostazol for RESTenosis
      (CREST) trial.
AB  - Restenosis of a segment of diseased coronary artery following metallic stenting
      is a common clinical problem and a major limitation of the procedure. Systemic
      pharmacologic interventions to deal with this problem have met with little
      success. Several small studies suggest that cilostazol, a phosphodiesterase III
      inhibitor whose pharmacologic properties include antiplatelet, antithrombotic,
      and vasodilatory effects; a beneficial effect on serum lipids; and in vitro
      inhibition of smooth muscle cell proliferation, may help prevent platelet
      aggregation and impede the accumulation of new intimal tissue in the stented
      artery. The Cilostazol for RESTenosis (CREST) trial will aim to evaluate more
      definitively the ability of cilostazol to prevent restenosis following
      uncomplicated stent implantation for de novo coronary artery stenosis. In this
      randomized, double-blind, multicenter study, 700 patients will receive
      clopidogrel, aspirin, and either cilostazol or placebo after successful
      intracoronary stent implantation. The primary endpoint is minimal luminal
      diameter (MLD) of the first lesion stented after 6 months; secondary endpoints
      include MLD in all lesions, mean percent diameter stenosis, target lesion
      revascularization, and major angiographic endpoints. Safety endpoints are
      abnormal complete blood count and liver function tests at 1, 3, and 6 months. The
      trial has been initiated, and enrollment is anticipated to be concluded in 2003.
      Cilostazol has properties that may reduce or avert in-stent coronary restenosis.
      The CREST trial is a large, rigorously conducted trial that may corroborate the
      favorable effects of cilostazol on coronary stent restenosis suggested by earlier
      studies.

PMID- 14579915
TI  - Bone marrow stimulation and left ventricular function in acute myocardial
      infarction.
AB  - BACKGROUND: Experimental studies have demonstrated that bone marrow stem cells
      can migrate into peripheral blood and regenerate damaged myocardium. HYPOTHESIS:
      Bone marrow stimulation might improve myocardial functional recovery after acute
      myocardial infarction (AMI). METHODS: In all, 104 consecutive patients with
      anterior wall AMI treated by primary coronary angioplasty and stenting within 12
      h after onset, and who underwent left ventriculography on admission and 6 months
      after discharge, were studied. Among these, 23 patients (Group 1) demonstrated
      transient appearance of immature blood cells including myelocytes, promyelocytes,
      and myeloblasts during hospital stay. Thirty-eight matched patients in whom no
      immature blood cells were detected were studied as a control group (Group 2).
      RESULTS: There was no significant difference in baseline characteristics between
      the two groups. There was no significant difference in left ventricular ejection
      fraction (EF) on admission between Group 1 (33 +/- 12%) and Group 2 (34 +/- 8%).
      In contrast, EF was significantly better in Group 1 (47 +/- 12%) than in Group 2
      (40 +/- 10%, p = 0.016) 6 months after discharge. CONCLUSION: The study suggests
      significantly greater improvement in left ventricular function in patients with
      AMI with sign of bone marrow stimulation than in matched patients with no sign of
      bone marrow stimulation.

PMID- 14579916
TI  - Asymmetrical dimethylarginine: a novel risk factor for coronary artery disease.
AB  - BACKGROUND: Asymmetrical dimethylarginine (ADMA) is an endogenous competitive
      inhibitor of nitric oxide synthase and has been associated with systemic
      atherosclerosis; however, the role of ADMA in patients with coronary artery
      disease (CAD) has not been investigated. HYPOTHESIS: The present study was
      designed to determine whether the plasma ADMA level predicts the presence of CAD
      independently, and whether the plasma ADMA level correlates with the extent and
      severity of coronary atherosclerosis. METHODS: In all, 97 consecutive patients
      with angina and positive exercise stress test were enrolled prospectively for
      coronary angiography. According to the result of angiography, the subjects were
      divided into two groups: Group I (n = 46): patients with normal coronary artery
      or mild CAD (< 50% stenosis of major coronary arteries); Group 2 (n = 51):
      patients with significant CAD (> or = 50% stenosis of majorcoronary arteries).
      Plasma levels of ADMA and L-arginine were determined by high-performance liquid
      chromatography. In addition, we used coronary atherosclerotic score to assess the
      extent and severity of CAD. RESULTS: The plasma levels of ADMA in Group 2
      patients were significantly higher than those in Group 1 patients (0.66 +/- 0.17
      microM vs. 0.44 +/- 0.09 microM, p < 0.001); these were accompanied by
      significantly lower plasma L-arginine/ADMA ratio in patients with significant CAD
      (Group 1 vs. 2: 194.0 +/- 55.3 vs. 136.7 +/- 50.3, p < 0.001). In a multivariate
      stepwise logistic regression analysis, both plasma ADMA level and plasma L
      arginine/ADMA ratio were identified as independent predictors for CAD. Moreover,
      there were significant positive and negative correlations between coronary
      atherosclerotic score and plasma ADMA level as well as plasma L-arginine/ADMA
      ratio, respectively (plasma ADMA level: r = 0.518, p < 0.001; L-arginine/ADMA
      ratio: r = -0.430, p < 0.001). CONCLUSIONS: Both plasma ADMA level and plasma L
      arginine/ADMA ratio were useful in predicting the presence of significant CAD and
      correlated significantly with the extent and severity of coronary
      atherosclerosis. Our findings suggest that plasma ADMA level may be a novel
      marker of CAD.

PMID- 14579917
TI  - Magnetocardiography in coronary artery disease with a new system in an unshielded
      setting.
AB  - BACKGROUND: The noninvasive detection of coronary artery disease (CAD) remains a
      clinical challenge. Magnetocardiography is a completely noninvasive method that
      permits the registration of cardiac electrical activity at multiple sites in a
      plane above the chest cage without the need for electrodes. In contrast to the
      electrocardiogram (ECG) which suffers from boundary effects and a variety of
      potential artifacts (electrode placement, etc.) the MCG is unaffected by such
      impediments as the magnetic field is unaltered by surrounding tissues.
      HYPOTHESIS: Magnetocardiography with a newly developed single-channel system in
      an unshielded setting should be a better qualitative diagnostic tool than the
      standard ECG for the detection and assessment of CAD. METHODS: In all, 52
      patients with angiographically documented CAD and unimpaired ventricular function
      as well as 55 controls were included in this study. A standard 12-lead ECG was
      obtained in all subjects. The MCG recordings were taken from 36 positions under
      resting conditions. From these, current density vector maps were generated during
      the ST-T interval. Each map was then classified using a classification system
      with a scale from 0 (normal) to 4 (grossly abnormal). RESULTS: While the ECG was
      normal in all subjects, the MCG in the controls was classified as category 0, 1,
      or 2. However, in patients with abnormal coronary angiograms, mainly maps in
      categories 3 and 4 were seen (p < 0.05). CONCLUSION: A single-channel
      magnetometer in an unshielded setting reveals significant differences between
      normals and patients with CAD with normal ECG on the basis of current density
      reconstruction during the ST segment when measured under resting conditions. This
      method might be suitable for the noninvasive detection of CAD.

PMID- 14579918
TI  - Rapid effects of simvastatin on lipid profile and C-reactive protein in patients
      with hypercholesterolemia.
AB  - BACKGROUND: Rapid lowering of low-density lipoprotein (LDL) cholesterol levels as
      well as C-reactive protein (CRP) by administration of drugs may produce early
      benefit to the coronary endothelium in patients with coronary heart disease and
      reduce angina and coronary events after revascularization. Limited information
      has been available in evaluating a potentially effective first 2-week therapeutic
      approach for the treatment of patients with hypercholesterolemia using a statin.
      HYPOTHESIS: The study was undertaken to investigate whether a rapid LDL
      cholesterol and CRP reduction can be achieved by 2-week simvastatin therapy using
      a common lipid-lowering protocol in patients with hypercholesterolemia. METHODS:
      Forty-two patients were randomly assigned to 20 or 40 mg/day of simvastatin.
      Blood samples were drawn at Day 0 and at Day 14 for measuring lipid profile, CRP
      levels, and hepatic enzymes in all patients. RESULTS: The results showed that
      both doses of simvastatin (20 and 40 mg) induced significant reductions in total
      cholesterol (TC, 25 and 38%) and LDL cholesterol (31 and 46%) compared with
      baseline. However, the highest dose of simvastatin (40 mg) resulted in
      significantly greater reductions in TC and LDL cholesterol (p = 0.04, p = 0.02,
      respectively) compared with the group receiving 20 mg (p < 0.04, p < 0.02,
      respectively). A less significant reduction was observed in mean triglycerides
      (TG) level (16 and 25%) compared with TC and LDL cholesterol. There was no
      significant difference in mean high-density lipoprotein (HDL) cholesterol levels
      compared with baseline in either group. In addition, both doses of simvastatin
      induced significant reductions in mean CRP levels on Day 14 (22.3 and 23.1%) in a
      non dose-dependent manner (p < 0.001, respectively. CONCLUSIONS: Our data suggest
      that a common daily dose of simvastatin, especially 40 mg, is an effective 2-week
      therapy for patients with hypercholesterolemia, and benefit to the vascular
      endothelium can be derived quickly by reduction of CRP levels.

PMID- 14579919
TI  - Diagnosis of coronary vasospasm by detection of postischemic regional left
      ventricular delayed relaxation using echocardiographic evaluation with color
      kinesis.
AB  - BACKGROUND: Coronary vasospasm has been diagnosed by invasive provocative
      procedures during coronary arteriography. It would be useful to have a reliable,
      noninvasive, and safe diagnostic method for coronary vasospasm. Regional left
      ventricular (LV) diastolic dysfunction may persist without systolic dysfunction
      after an episode of coronary vasospasm. Color kinesis (CK) has been recently
      developed to facilitate the echocardiographic evaluation of regional wall motion.
      HYPOTHESIS: Color kinesis may be useful for diagnosis of coronary vasospasm by
      detection of postischemic regional LV diastolic wall motion abnormality. METHODS:
      Fifty-one consecutive patients with the last chest symptom within 2 weeks (4 +/-
      3 days) were studied echocardiographically. Regional fractional area change
      during the first 30% of LV filling time in percentage of the segmental end
      diastolic area change (CK diastolic index) was used to identify diastolic
      endocardial motion asynchrony. RESULTS: After diagnostic coronary arteriography
      with spasm provocation, 26 patients were diagnosed with coronary spastic angina
      (CSA) and the other 25 with chest pain syndrome (CPS). Regional delayed
      relaxation (CK-diastolic index < or = 50%) or diastolic asynchrony had been
      observed in at least one region in 25 (96%) patients with CSA, whereas it had
      been noted in 2 (8%) patients with CPS. In 17 (65%) patients with CSA, it had
      been detected in multiple vascular territories, suggesting multivessel spasm. The
      diastolic asynchrony disappeared in CSA after a month of angina-free period.
      CONCLUSION: Analysis of CK images allows identification of regional LV delayed
      relaxation or diastolic asynchrony in patients with coronary vasospasm,
      differentiating them from patients with chest pain syndrome (sensitivity 96%,
      specificity 92%).

PMID- 14579920
TI  - Relation of ultrasonic tissue characterization with integrated backscatter to
      contractile reserve in patients with chronic coronary artery disease.
AB  - BACKGROUND: Previous studies have shown that viable but stunned myocardium
      displays contractile reserve and exhibits cardiac cycle-dependent variations of
      integrated backscatter (CVIB), whereas infarcted myocardium does not. HYPOTHESIS:
      This study was designed to clarify whether assessment of the acoustic properties
      of the myocardium can predict contractile reserve in patients with chronic
      coronary artery disease (CAD). METHODS: In all, 21 patients with chronic CAD and
      19 normal control subjects were studied. The magnitude of CVIB of the myocardium
      was measured in the basal and mid segment of the anterior septum and posterior
      wall of the left ventricle, using a real-time, two-dimensional integrated
      backscatter imaging system. The results were compared with the percent systolic
      wall thickening and the wall motion before and after revascularization. The wall
      motion was graded as normal, hypokinetic, or akinetic, and contractile reserve
      was considered present when an akinetic or hypokinetic segment improved after
      revascularization. RESULTS: The average magnitude of CVIB was lower among
      dysfunctional segments of CAD than among normal segments of controls (3.73 +/-
      1.71 vs. 6.35 +/- 0.69, p < 0.001). Of the 77 segments examined, 38 showed
      reversible dysfunction. Before revascularization, percent systolic wall
      thickening was similar among segments showing contractile reserve compared with
      those with persistent dysfunction myocardium (17.97 +/- 8.41 vs. 16.83 +/- 6.37%,
      p = 0.19), and the mean CVIB was significantly greater in segments with than in
      those without contractile reserve (4.73 +/- 1.47 vs. 2.75 +/- 1.31, p < 0.001).
      The CVIB above 3 dB before percutaneous transluminal coronary angioplasty
      predicted segments with contractile reserve with a sensitivity and specificity of
      84.2 and 79.5%, respectively. CONCLUSIONS: Cardiac cycle-dependent variations of
      integrated backscatter reflected myocardial contractility and functional capacity
      of the myocardium. They predicted segmental contractile reserve in patients with
      CAD.

PMID- 14579921
TI  - Profiles in cardiology. Hugo Kronecker and the dependence of heart function on
      blood supply.

PMID- 14579922
TI  - Cell therapy and homeland security: funding opportunities for biomedical
      research.

PMID- 14579923
TI  - Human cord blood-derived mesenchymal stem cells home and survive in the marrow of
      immunodeficient mice after systemic infusion.
AB  - Bone marrow is the residence site of mesenchymal stem cells (MSC), which upon
      commitment and maturation develop into several mesenchymal phenotypes. Recently,
      we have described the presence of MSC in human cord blood (cbMSC) and informed
      that their properties are the same as those for MSC obtained from adult bone
      marrow. In this study we have investigated the capability of transplanted cbMSC
      to home and survive in the marrow of unconditioned nude mice. cbMSC utilized for
      transplantation studies were characterized by morphology, differentiation
      potential, and immunophenotype. After transplantation by systemic infusion, human
      DNA (as detected by PCR amplification of human-specific beta-globin gene) was
      detected in the marrow of recipients as well as in ex vivo-expanded stromal cells
      prepared from the marrow of transplanted animals. These results demonstrate
      homing and survival of cbMSC into the recipient marrow and also suggest a
      mesenchymal-orientated fate of engrafted cells, because human DNA was also
      detected in cells of other recipient tissues, like cardiac muscle, teeth, and
      spleen.

PMID- 14579924
TI  - Bridging a patient with acute liver failure to liver transplantation by the AMC
      bioartificial liver.
AB  - Recently a phase I clinical trial has been started in Italy to bridge patients
      with acute liver failure (ALF) to orthotopic liver transplantation (OLT) by the
      AMC-bioartificial liver (AMC-BAL). The AMC-BAL is charged with 10 x 10(9) viable
      primary porcine hepatocytes isolated from a specified pathogen-free (SPF) pig.
      Here we report a patient with ALF due to acute HBV infection. This patient was
      treated for 35 h by two AMC-BAL treatments and was bridged to OLT. There was
      improvement of biochemical and clinical parameters during the treatment. No
      severe adverse events were observed during treatment and follow-up of 15 months
      after hospital discharge. Possible porcine endogenous retrovirus (PERV) activity
      could not be detected in the patient's blood or blood cells up to 12 months after
      treatment.

PMID- 14579925
TI  - Characterization of long-term survival of syngeneic hepatocytes in rat
      peritoneum.
AB  - Hepatocyte transplantation is a potential therapy for both acute and chronic
      hepatic insufficiency and also for treatment of inborn errors of metabolism
      affecting the liver. The peritoneum is one site for implantation and has several
      advantages: cells implanted there can be easily identified and observed, and it
      has a relatively large capacity. Long-term survival using "pure" hepatocytes in
      the peritoneum have been disappointing. We hypothesized that cotransplantation of
      hepatocytes with nonparenchymal cells would help maintain differentiated
      hepatocyte function. Rat liver cells transplanted intraperitoneally into August
      rats were sacrificed at 7 days, 1, 3, 6, 9, and 12 months and analyzed for
      presence, basal proliferation, and functionality of hepatocytes. To demonstrate
      that ectopic hepatocytes remained susceptible to exogenous growth factors
      affecting cell proliferation, rats 9 and 12 months after transplantation were
      stimulated with tri-iodothyronine and KGF. Hepatocytes were identified 7 days to
      >12 months, by H&E and immunohistochemically, as ectopic islands in the omental
      fat. Functionality was confirmed by glycogen deposition. Basal proliferation in 7
      day rats was 28.0 +/- 10/1000 hepatocytes in ectopic islands (cf. 5.70 +/-
      2.7/1000 in recipient liver). Proliferation in ectopic islands was greater than
      host liver. Growth factor-stimulated proliferation in ectopic islands induced a
      70-fold increase in DNA synthesis. In conclusion, hepatocytes transplanted with
      nonparenchymal cells survive, proliferate, and function in the peritoneum of
      normal rats, and respond to exogenous growth stimuli. Their survival and
      proliferation in the presence of a normal functioning liver has implications for
      the potential use of the peritoneal site clinically for supplementation of liver
      function in metabolic disorders.

PMID- 14579926
TI  - Hypothermic storage and cryopreservation of hepatocytes: the protective effect of
      alginate gel against cell damages.
AB  - Hepatocyte-based therapy has been proposed as an alternative to organ
      transplantation in the treatment of liver disorders. In the clinical context, a
      major issue is the constant supply of quality assurance-controlled hepatocytes,
      thereby requiring their cold storage in good conditions. We have analyzed the
      protective effects of alginate entrapment of rat hepatocytes after either 24 or
      48 h of hypothermic storage or cryopreservation on the cell viability, cell
      yield, both mitochondrial and other cytoplasmic functional activities, and
      apoptosis. Decrease in viability, as evaluated by the MTT inclusion test, was 4%
      and 13% (24 h at 4 degrees C), 15% and 33% (48 h at 4 degrees C), and 9% and 19%
      (liquid nitrogen) for entrapped and free suspended hepatocytes, respectively.
      Viable cell yields were 86 +/- 8% and 51 +/- 6% for cryopreserved entrapped and
      free suspended hepatocytes, respectively. The mitochondrial (MTS assay), 7
      ethoxyresorufin O-deethylase (EROD), and glutathione-S-transferase (GST)
      activities were better preserved in entrapped than in free suspended hepatocytes.
      Both hypothermic storage and cryopreservation were found to induce early caspase
      3-like activities, being always much lower in entrapped hepatocytes, particularly
      after cryopreservation (98.4 +/- 42.4 vs. 6.4 +/- 4.0 fluorescence arbitrary
      units/hours/microg protein). Thus, cold-induced apoptosis in hepatocytes can be
      significantly reduced following their entrapment within alginate gel beads and
      this is associated with an improvement of both their viability and function.

PMID- 14579927
TI  - Hepatocyte isolation and transplantation in the pig.
AB  - Hepatocyte transplantation (HTX) has received great expectation for the treatment
      of a wide spectrum of liver diseases. Considering the severe shortage of human
      livers for hepatocyte isolation, porcine hepatocytes are an attractive
      alternative to normal human hepatocytes. To develop such therapy, establishment
      of an efficient hepatocyte isolation and transplantation model that enables
      accurate assessment of safety and efficacy of HTX is extremely important. Porcine
      hepatocytes were isolated from a surgically removed liver segment with a four
      step retrograde perfusion using dispase and collagenase. The resultant
      hepatocytes of > 84% viability were used for transplantation experiment in a pig
      model of acute liver failure induced by intravenous administration of D
      galactosamine (D-gal) (0.5 mg/kg). Twenty-four hours after D-gal injection,
      transplantation of freshly isolated porcine hepatocytes (1 x 10(9)) was safely
      conducted and prolonged the survival of D-gal-treated pigs. We describe an
      efficient porcine hepatocyte isolation and subsequent cell transplantation in
      pigs with D-gal-induced liver failure.

PMID- 14579928
TI  - Maintenance of cold-preserved porcine hepatocyte function with UW solution and
      ascorbic acid-2 glucoside.
AB  - Normal human hepatocytes are an ideal source of liver-targeted cell therapies,
      such as hepatocyte transplantation and bioartificial livers, but availability of
      human donor livers for liver cell isolation is severely limited. To effectively
      utilize scarce donor organs for cell therapies, it is of extreme importance to
      establish an efficient isolation technique and an effective cold preservation
      solution for transportation of isolated cells. A lateral segment of the liver was
      surgically resected from pigs weighing 10 kg and a four-step collagenase and
      dispase digestion was conducted. Isolated hepatocytes were subjected to 8-h cold
      storage on ice. The following preservation solutions were tested: 1) University
      of Wisconsin (UW) solution, 2) UW with 100 microg/ml of ascorbic acid-2 glucoside
      (AA2G), 3) 100% fetal bovine serum (FBS), and 4) Dulbecco's modified Eagle's
      medium (DMEM) supplemented with 100% FBS. The mean viability of porcine
      hepatocytes was 95.5 +/- 2.5% when isolated in three independent experiments.
      Viability, plating efficiency, membrane stability, and ammonia metabolic capacity
      of cold-preserved hepatocytes were significantly better maintained by the use of
      UW solution. When AA2G (100 microg/ml) was combined with UW solution, such
      parameters were further improved. It was explained by inhibition of caspase-3
      activation and retention of ATP at high levels of hepatocytes preserved with UW
      solution containing AA2G. The present work demonstrates that a combination of UW
      solution with AA2G (100 microg/ml) would be a useful cold preservation means for
      the development of cell therapies.

PMID- 14579929
TI  - Cryopreservation of primarily isolated porcine hepatocytes with UW solution.
AB  - Development of liver-targeted cell therapies, such as hepatocyte transplantation
      and bioartificial livers, requires a large amount of functional hepatocytes as
      needed. To achieve this development, establishing an excellent cryopreservation
      method of hepatocytes is an extremely important issue. Therefore, we performed a
      comparative review of cryoprotective effects of various cryopreservation
      solutions using primarily isolated porcine hepatocytes. Porcine hepatocytes were
      isolated with a four-step dispase and collagenase perfusion method. The obtained
      hepatocytes with the initial viabilities of 76%, 84%, and 96% were assigned to
      the following four groups for cryopreservation at -80 degrees C: Dulbecco's
      modified Eagle's medium (DMEM) + 10% fetal bovine serum (FBS) + 12% dimethyl
      sulfoxide (DMSO) (group A), University of Wisconsin (UW) solution + 12% DMSO
      (group B), Cell Banker 1 (group C), and Cell Banker 2 (group D). The hepatocytes
      in each group were thawed at 3 days, 10 days, and 5 months of cryopreservation
      and subjected to comparative analyses, including viability, plating efficiency,
      LDH release, ammonia removal test, and lentiviral gene transfer. These parameters
      were the most favorable in the hepatocytes cryopreserved with UW solution.
      Approximately 5% of thawed cryopreserved porcine hepatocytes expressed LacZ
      activity after lentiviral transduction. Intrasplenic transplantation of UW
      solution-cryopreserved hepatocytes improved the survival of rats treated with D
      galactosamine. UW solution maintained the functions of cryopreserved porcine
      hepatocytes.

PMID- 14579930
TI  - Factors influencing insulin secretion from encapsulated islets.
AB  - Adequate regulation of glucose levels by a microencapsulated pancreatic islet
      graft requires a minute-to-minute regulation of blood glucose. To design such a
      transplant, it is mandatory to have sufficient insight in factors influencing the
      kinetics of insulin secretion by encapsulated islets. The present study
      investigates factors influencing the glucose-induced insulin response of
      encapsulated islets in vitro. We applied static incubations and did the following
      observations. (i) Small islets (90-120 microm) showed a similar instead of a
      lower glucose-induced insulin response, suggesting that inclusion of only small
      islets, which are associated with lower protrusion and failing rates, has no
      consequences for the functional performance of the graft. (ii) A capsule diameter
      of 800 microm showed identical rather than lower glucose-induced insulin
      responses as smaller, 500-microm capsules. (iii) Capsule membranes constructed
      with a conventional permeability interfered with diffusion of insulin, as
      illustrated by a lower response of islets in capsules with a 10-min poly-L-lysine
      (PLL) membrane than islets in capsules with a 5-min PLL membrane. (iv)
      Irrespective of the tested porosity, the capsules provided sufficient
      immunoprotection because the 10-min PLL membranes did block diffusion of the
      cytokines IL-1beta (17 kDa) and TNF-alpha (70 kDa) while the 5-min PLL membranes
      interfered with the diffusion of the vast majority of the cytokines. We conclude
      that capsules containing small islets (90-120 microm) and a membrane with a lower
      permeability than routinely applied is preferred in order to obtain a graft with
      adequate glucose-induced insulin responses.

PMID- 14579931
TI  - Influence of VEGF on the viability of encapsulated pancreatic rat islets after
      transplantation in diabetic mice.
AB  - After pancreatic islet transplantation, insufficient blood supply is responsible
      for the loss of islet viability. The aim of our study was: 1) to determine the
      influence of vascular endothelial growth factor (VEGF) on the survival of
      encapsulated rat islets transplanted into healthy and diabetic mice and 2) to
      evaluate the metabolic efficiency of the VEGF-supplemented grafts. Twenty-four
      hours after culture, 50 rat islets immobilized into collagen in the presence of
      VEGF (100 ng/ml) and encapsulated (AN69 membrane, HOSPAL) were grafted in the
      peritoneal cavity of healthy or streptozotocin-induced diabetic mice (n = 6).
      Seven, 14, and 28 days after implantation, the encapsulation device and tissue
      surrounding the device were removed and the following parameters were analyzed:
      the number and the diameter of buds, the distance between devices and buds, the
      amount of cellular adhesion on the capsule surface, and the level of insulin
      secreted by encapsulated islet. For reversal of diabetes, 1000 rat islets
      encapsulated in the presence of VEGF were implanted in the peritoneal cavity of
      diabetic mice and fasting glycemia was analyzed. After 7 days of islet
      implantation in the absence of VEGF, the bud diameter was 16.1 +/- 6.9 microm in
      diabetic mice and 34.4 +/- 3.9 microm in healthy mice. However, the number of
      buds increased by a factor 2.5 in the presence of VEGF in both types of mice.
      Furthermore, when islets were transplanted in the presence of VEGF, the distance
      between the device and the buds was significantly decreased in both types of mice
      (p < 0.001) after 7, 14, and 28 days of islet implantation. Capsule analysis
      showed a decrease in cellular adhesion when the islets were encapsulated in the
      presence of VEGF. Insulin secretion of the islets was higher in the presence of
      VEGF compared with islets alone at all steps of the study. When 1000 rat islets
      were transplanted in the presence of VEGF, the glycemia level decreased to 6.2 +/
      0.8 mmol/L after 3 days and remained stable until at least 28 days. In contrast,
      in the absence of VEGF, the initial decrease in the glucose level was rapidly
      followed by a relapse in hyperglycemia. In summary, VEGF increased the viability
      of engrafted encapsulated islets, increasing the duration of a normalized
      glycemia in diabetic mice following transplantation. Local adjunction of VEGF may
      therefore improve the clinical outcome of islet transplantation.

PMID- 14579932
TI  - Activated porcine embryonic brain endothelial cells induce a proliferative human
      T-lymphocyte response.
AB  - Transplantation of allogeneic embryonic neural tissue is a potential treatment
      for patients with Parkinson's and Huntington's diseases. The supply of human
      donor tissue is limited, and alternatives such as the use of animal (e.g.,
      porcine) donor tissue are currently being evaluated. Before porcine grafts can be
      used clinically, strategies to prevent neural xenograft rejection must be
      developed. Knowledge on how human T lymphocytes recognize porcine embryonic
      neural tissue would facilitate the development of such strategies. To investigate
      the ability of porcine embryonic brain microvascular endothelial cells (PBMEC) to
      stimulate human T-cell proliferation, PBMEC were immuno-magnetically isolated and
      cocultured with purified human CD4 or CD8 single-positive T cells. PBMEC had a
      cobblestone-like growth pattern and expressed the endothelial cell markers CD31
      and CD106. PBMEC stimulated with the supernatant of phytohemagglutinin-activated
      porcine peripheral blood mononuclear cells or porcine IFN-gamma, but not
      nonstimulated PBMEC, induced proliferation of both CD8 and CD4 T cells as
      assessed by [3H]thymidine incorporation. Flow cytometric analyses showed that the
      degree of CD8 and CD4 T cell proliferation correlated with the expression levels
      of class I and II major histocompatibility complex (MHC) antigens, respectively.
      PBMEC expressed a CTLA-4/Fc-reactive molecule, most likely CD86, suggesting that
      these cells are able to deliver a costimulatory signal to the T cells. Human TNF
      alpha, but not human IFN-gamma, induced class I, but not class II, MHC expression
      on PBMEC. Within a neural graft or the regional lymph nodes, PBMEC might
      stimulate human T cells via the direct pathway, and should therefore be removed
      from the donor tissue prior to transplantation.

PMID- 14579933
TI  - Transplanted endothelial progenitor cells augment the survival areas of rat
      dorsal flaps.
AB  - Endothelial progenitor cells (EPCs) have been identified in peripheral blood, and
      have been reported to be incorporated into ischemic regions such as the ischemic
      hindlimb. In this study, we examined whether or not transplantation of EPCs is
      useful for salvaging surgical flaps in vivo. At the same time, we quantitatively
      compared the neovascularization ability of transplanted EPCs and that of mature
      endothelial cells (ECs). ECs obtained from the aorta of rats by explantation and
      passaged several times were used in the present study. EPCs were obtained from
      the blood of rat hearts. The blood samples were separated by density gradient
      centrifugation. Light-density mononuclear cells (MNCs) were collected and
      cultured on plastic plates coated with rat plasma vitronectin. Cells attached at
      day 7 of culture were deemed to be EPCs. Then PBS (control), ECs, or EPCs (3.0 x
      10(5) suspended in 1.0 ml PBS) were injected at the middle of a flap. Seven days
      after surgery, the survival lengths of the flaps were evaluated. EPC-transplanted
      groups revealed statistically significant augmentation of survival length
      compared with the other two groups (p < 0.003). EPC-transplanted groups had
      significantly more angiographically detectable blood vessels (p < 0.003) and
      significantly higher capillary density (p < 0.03) than the other two groups.
      Confocal microscopy revealed that EPCs were incorporated into enhanced
      neovascularization. These results suggest that transplantation of EPCs may be
      useful for salvaging surgical flaps, and EPCs are superior to ECs in
      neovascularization ability.

PMID- 14579934
TI  - Decellularized native and engineered arterial scaffolds for transplantation.
AB  - More than 570,000 coronary artery bypass grafts are implanted each year, creating
      an important demand for small-diameter vascular grafts. For patients who lack
      adequate internal mammary artery or saphenous vein, tissue-engineered arteries
      may prove useful. However, the time needed to tissue engineer arteries (7 weeks
      or more) is too long for many patients. Decellularized cadaveric human arteries
      are another possible source of vascular conduit, but limited availability and the
      potential for disease transmission limit their widespread use. In contrast,
      decellularized tissue-engineered arteries could serve as grafts for immediate
      implantation, as scaffolds onto which patients' cells could be seeded, or as
      carriers for genetically engineered cells to aid cell transplantation. The goal
      of this study was to quantify the effects of decellularization on vascular matrix
      and mechanical properties. Specifically, we compared cellular elimination,
      extracellular matrix retention, and mechanical characteristics of porcine carotid
      arteries before and after treatment with three decellularization methods. In
      addition, for the first time, tissue-engineered arteries were decellularized.
      Decellularized native arteries were also used as a scaffold onto which vascular
      cells were seeded. These studies identified a decellularization method for native
      and engineered arteries that maximized cellular elimination, without greatly
      compromising mechanical integrity. We showed that engineered tissues could be
      decellularized, and demonstrated the feasibility of reseeding decellularized
      vessels with vascular cells.

PMID- 14579935
TI  - Novel technique for suspension culture of autologous chondrocytes improves cell
      proliferation and tissue architecture.
AB  - We have developed a new and simple method of chondrocyte suspension culture using
      a spinner bottle with rotation of the matrices. We compared the characteristics
      of chondrocytes cultured by this method with those grown in standard monolayer
      cultures. We also determined the optimal nutritional medium for suspension
      cultures. Periosteum explants seeded with chondrocytes were grown in monolayer
      and suspension cultures under three conditions: in medium with no additive
      (control), with 10% fetal bovine serum (FBS), or with 10% autologous serum (AS).
      After culturing, the explants were harvested, processed for histology, and
      stained with hematoxylin-eosin or TUNEL, or immunostained for type I, II, and III
      collagen, and Ki-67 antigen. In monolayer cultures, the attachment of the
      chondrocytes to the periosteum was weak and the superficial layer consisted of
      fibrotic tissue and few nucleated cells. Collagen type II staining was strong,
      but types I and II were weak. Among the suspension cultures the AS group produced
      the thickest layer of chondrocytes with the fewest apoptotic cells. The
      superficial layer of cartilage in these cultures stained positive for type I and
      III collagen and Ki-67 antigen. Among the suspension cultures, total chondroitin
      and chondroitin-4 sulfate (C-4S) concentration was highest in the AS group, while
      prostaglandin E2 (PGE2) was highest in the FBS group. In summary, our new method
      of suspension culture of periosteal explants using rotational matrices combined
      with AS nutritional media was the most effective method for maintaining the bond
      between the chondrocyte layer and periosteum, as well as the production of type I
      and III collagen in the superficial layer.

PMID- 14579936
TI  - Angiotensin-converting enzyme inhibitor withdrawal and ACE gene polymorphism.
AB  - AIMS: Withdrawal of angiotensin-converting enzyme (ACE) inhibitors may affect the
      progression of chronic renal failure and an insertion/deletion (I/D) polymorphism
      of the ACE gene may influence it. METHODS: We retrospectively collected patients
      with chronic glomerulonephritis and benign nephrosclerosis who discontinued ACE
      inhibitor use. The relationship between the decline of renal function after the
      withdrawal and the influencing factors such as ACE gene polymorphism, blood
      pressure and proteinuria were evaluated using multiple regression analysis.
      RESULTS: Forty-two patients (initial serum creatinine 0.5 - 6.5 mg/dl) had been
      treated and discontinued ACE inhibitor use. Only patients with the II or DI
      genotypes of the ACE gene developed the deterioration of renal function, starting
      at 2 months after the withdrawal. Stepwise regression analysis revealed that the
      level of proteinuria after the withdrawal, presence of the insertion of ACE gene
      and serum creatinine level at the time of withdrawal mainly influenced the
      decline of renal function after the withdrawal (adjusted R2 = 0.48). CONCLUSION:
      Withdrawal of ACE inhibitor causes the deterioration of renal function in
      patients with the II or DI genotypes, high proteinuria after the withdrawal, and
      high serum creatinine level at the withdrawal, which probably causes the rebound
      increase in serum ACE activity.

PMID- 14579937
TI  - Secondary focal segmental glomerulosclerosis in non-obese patients with increased
      muscle mass.
AB  - BACKGROUND: Secondary focal segmental glomerulosclerosis (FSGS) is a pattern of
      glomerular injury mediated by hyperfiltration and other adaptive structural
      functional responses. We describe 3 non-obese patients with elevated body mass
      index (BMI) owing to increased muscle mass who had renal biopsy findings favoring
      a form of secondary FSGS. METHODS: Clinical and pathologic data were obtained on
      3 patients with 1) renal biopsy findings of focal segmental and/or global
      glomerulosclerosis with glomerulomegaly; 2) BMI > or = 30; 3) body fat percentage
      < 20%; 4) "highly muscular" appearance, and 5) proteinuria > or = 1 g/d without
      nephrotic syndrome. 24-hour urine creatinine excretion was used to estimate lean
      body mass and percentage body fat. RESULTS: The 3 patients were males (age 38 -
      48 years) employed in jobs requiring strenuous physical activity. BMIs ranged
      from 30.4 - 32.1 kg/m2 with body fat percentages of 12.9 - 16.8%. Creatinine
      clearances at time of biopsy ranged from 113 - 208 ml/min. Renal biopsies showed
      focal segmental and/or global glomerulosclerosis affecting a minority of
      glomeruli with glomerular hypertrophy and minimal (mean 15%) foot process
      effacement. Treatments included angiotensin-converting enzyme inhibitor,
      angiotensin II receptor blocker, or weight loss. Over a mean follow-up time of
      24.3 months, serum creatinine remained stable and proteinuria decreased in all
      patients. CONCLUSIONS: Non-obese patients with increased BMI due to elevated
      muscle mass are at risk of developing a secondary form of FSGS that resembles
      obesity-related glomerulopathy.

PMID- 14579938
TI  - Combined T- and B-cell activation in childhood steroid-sensitive nephrotic
      syndrome.
AB  - BACKGROUND: Growing evidence shows that steroid-sensitive nephrotic syndrome
      (SSNS) is the result of a primary T-cell disturbance and leads to secondary
      anatomical and functional, however, not to immunological glomerular changes. In
      addition, immunoglobulin abnormalities in SSNS indicate a role of B-cell
      involvement. PATIENTS AND METHODS: We therefore analyzed T- and B-cell activation
      markers in children with SSNS at different stages of the disease including
      different treatment regimens by measuring the soluble IL-2 receptor (sCD25) and
      the soluble low-affinity IgE receptor (sCD23), respectively. Seventy-five
      patients with SSNS (median age 8.0, range 2.5 - 18 years) were studied, 33 in
      relapse (RL) including 21 patients relapsing during alternate-day steroids (RL
      SD). Forty-two patients were studied in remission (RM; 14 off treatment and 28 on
      alternate-day steroids (RM-AD)) and 22 age-matched children served as controls.
      RESULTS: Serum concentrations of sCD25 were increased in RL (113.6 +/- 19.5
      micromol/l) compared to RM (79.8 +/- 8 micromol/l, p < 0.02) and controls (74.8
      +/- 0.9 micromol/l, p < 0.02). Patients with RL-SD did not have elevated sCD25.
      In relapse, sCD25 was inversely correlated with age (R = -0.36, p < 0.04) and
      positively correlated with total IgG (R = 0.37, p < 0.04). Urinary excretion of
      sCD25 was also significantly elevated in RL of SSNS compared to RM and controls
      (71.2 +/- 11.9 micromol/g creatinine vs. 39.1 +/- 4.8 and 32.0 +/- 4.2
      micromol/g, p < 0.05). Serum levels of sCD 23 were significantly elevated in RL
      (6.22 +/- 0.65 microg/l) compared to RM (3.1 +/- 0.83 microg/l, p < 0.02) and to
      controls (3.4 +/- 0.93 microg/l). The highest values, however, were found in RL
      SD (7.8 +/- 1.7 microg/l) vs. untreated RL (p < 0.007) and RM-AD (p < 0.002). In
      untreated RL there was a significant correlation of sCD23 and total IgE (R =
      0.67, p < 0.02) and in RL-SD with total IgG (R = 0.45, p < 0.05). sCD23 and sCD25
      were not correlated with each other. CONCLUSION: These data document parallel
      abnormalities of both CD23-mediated B as well as CD25-mediated T-cell activation
      and suggest that SSNS is not solely a disorder of T-cell dysfunction.

PMID- 14579939
TI  - Elevated serum C-reactive protein associates with deterioration of renal function
      in transplant recipients.
AB  - AIM: Since t he elevated concentration of serum C-reactive protein (CRP) is a
      sensitive indicator of underlying inflammation, we investigated the association
      between serum CRP during the initial 6 post-transplantation months and
      histopathological changes in the 6-month protocol biopsies in 79 patients. We
      stained the biopsies for CRP and C3 to elucidate a possible role of CRP in renal
      injuries. RESULTS: Forty patients showed no or minimal (Grade 0-1) tubular
      atrophy or interstitial fibrosis and 39 patients mild to moderate (Grade > or =
      2) chronic histopathological changes. The latter group had had higher
      concentration of CRP during the first 6 post-transplant months. Because the
      histopathological changes predict poor long-term prognosis, we followed--from 6th
      month onwards--40 patients who had no or minimal histopathologic changes, and
      analyzed the association between CRP elevation and development of chronic
      allograft dysfunction. During this follow-up period (mean 51, range 14-72
      months), 23 of 40 patients retained normal CRP level (Group A, mean CRP 1.12
      mg/l), and 17 patients had elevated CRP concentrations (Group B, mean CRP 4.16
      mg/l); 24-hour creatinine clearance improved or remained the same in all Group A
      patients, whereas it decreased in 7 of 17 (41%) of Group B patients (p < 0.001).
      In Group B patients, the annual change of creatinine clearance correlated
      inversely with the mean CRP concentration (r = -0.682, p < 0.01). CONCLUSION: Our
      results show that histological changes in 6-month biopsies were more prominent in
      patients with more transplantation-associated complications, infections and
      frequently higher CRP levels during the initial 6 post-transplant months than in
      those with lower CRP levels. During post-biopsy follow-up, we found low-grade
      systemic inflammation--measured as elevated CRP--to associate with impairment of
      graft function in patients with no or minimal histological findings in 6-month
      biopsies, and permanently low CRP to rule out chronic allograft dysfunction.

PMID- 14579940
TI  - Paraoxonase (Pon1) Q192R polymorphism and serum Pon1 activity in diabetic
      patients on maintenance hemodialysis.
AB  - Patients with diabetic nephropathy have an increased risk of coronary heart
      disease (CHD). Paraoxonase (Pon1) is a high-density lipoprotein- (HDL) associated
      enzyme that protects low-density lipoprotein from oxidation and also protects
      against atherosclerosis. We investigated the relationship of serum Pon1 activity,
      Pon1 Q192R polymorphism and HDL-C level to type 2 diabetes mellitus (DM) in
      patients on maintenance hemodialysis (HD). DM patients (n = 56, F/M = 17/39, aged
      64.5 +/- 7.5 years) and non-DM patients (n = 89, F/M = 28/61, aged 62.7 +/- 8.3
      years) under HD were included in this study. Salt-stimulated serum Pon1
      activities were measured using paraoxon as a substrate. Pon1 Q192R polymorphism
      was detected by the mutagenically separated polymerase chain reaction. DM
      patients on HD had significantly lower HDL-C levels and serum Pon1 activities
      than non-DM patients on HD (657 +/- 277 vs. 763 +/- 257 IU/l, p < 0.01). The
      distribution of Pon1 Q 192R genotypes in all subjects did not differ from that
      predicted from the Hardy-Weinberg equilibrium. Serum Pon1 activities in both DM
      and non-DM patients on HD were regulated by Pon1 Q192R polymorphism: RR > QR >
      QQ. However, the reduced Pon1 activities in DM patients on HD were related to DM
      independent of the Pon1 genotype: reduced Pon1 activity was related to DM in RR
      carriers. Serum Pon1 activities were positively correlated with HDL-C levels. The
      association between HDL-C and DM in hemodialyzed patients was independent of Pon1
      activity as assessed by an analysis of variance. But the relation between Pon1
      activity and DM was modified by HDL-C levels: significantly when HDL-C was below
      50 mg/dl, but not significantly when HDL-C was above 50 mg/dl. The results of a
      logistic regression analysis show that reduced serum Pon1 activities and low HDL
      C levels were additively associated with DM. In conclusion, Pon1 status and HDL
      levels are independently associated with DM in patients on hemodialysis and may
      contribute to the increased risk of CHD in diabetic nephropathy.

PMID- 14579941
TI  - Parathyroid hormone and mineral metabolism do not have significant impact on
      pulse pressure in patients undergoing peritoneal dialysis.
AB  - BACKGROUND: Pulse pressure, a surrogate for arterial stiffness, has been shown to
      have substantial impact on predicting patient mortality. Excess cardiac risk in
      the end-stage renal disease population could be mediated by elevated arterial
      stiffness, which might in turn result from secondary hyperparathyroidism and
      abnormal calcium metabolism. METHODS: A cross-sectional study was carried out to
      examine a possible relationship between pulse pressure and secondary
      hyperparathyroidism among 126 prevalent patients undergoing continuous ambulatory
      peritoneal dialysis. RESULTS: The mean values for calcium and intact parathyroid
      hormone level were 2.48 mmol/l and 50.5 pmol/l, respectively. No correlation was
      found between pulse pressure and the plasma PTH levels (r = -0.15, p = 0.11) or
      calcium-phosphorus product (r = -0.08, p = 0.38). In a multivariate regression
      analysis, on the other hand, elevated pulse pressure was directly associated with
      age (2.1 mmHg per 10-year increase) and the presence of diabetes mellitus (6.9
      mmHg) (both p < 0.001). Pulse pressure was also inversely associated with
      hemoglobin level. CONCLUSION: The magnitude of arterial pulse pressure in a
      peritoneal dialysis population was not significantly affected by parathyroid
      disease and alterations in mineral metabolism with end-stage renal disease. In
      agreement with similar observations in hemodialysis populations, it is postulated
      that abnormalities in conduit vessel stiffness (as measured by pulse pressure)
      are substantially caused by atherosclerosis, in which intimal calcification (as
      distinct from medial calcification in the context of hyperparathyroidism) plays a
      more important role.

PMID- 14579942
TI  - Corynebacterium striatum peritoneal dialysis catheter exit site infection.
AB  - BACKGROUND: Regarded as normal flora of the human skin and mucus membranes, non
      diphtheria corynebacteria are frequently dismissed as contaminants or harmless
      colonizers. Recently, the pathogenic potential of C. striatum has been realized
      in immunocompromised patients with indwelling medical devices and previous
      antibiotic exposure. OBJECTIVE: We report here the diagnosis, treatment and
      clinical outcome of a peritoneal dialysis patient with a C. striatum infection of
      the catheter exit site. The aim is to present important features to assist in
      identifying clinically significant infections and provide guidelines for
      treatment. RESULTS: An immunocompromised patient with previous antimicrobial
      exposure developed an acute dialysis catheter exit site infection. C. striatum
      was isolated in pure growth. After initial treatment failure with oral
      antibiotics and intensified wound care, a satisfactory outcome was ultimately
      achieved without relapse or loss of the catheter with a 1-month course of
      vancomycin, 1 g intravenously, administered at 5-day intervals. CONCLUSIONS: The
      virulent capacity of Corynebacterium species should not be underestimated,
      particularly in high-risk patients. The presence of clinical signs of infection
      with isolation of the organism in pure culture and the presence of Gram-positive
      rods on direct Gram stain, especially in association with a leukocyte reaction,
      supports a cause and effect relationship. Because corynebacteria may be
      multiresistant, susceptibility testing should be performed on clinically
      significant isolates. Initial antibiotic selection is influenced by the severity
      of the infection, however, current experience favors vancomycin in significant
      infections.

PMID- 14579943
TI  - Younger onset myeloperoxidase-specific antineutrophil cytoplasmic antibody- (MPO
      ANCA) related glomerulonephritis accompanied with nephrotic syndrome.
AB  - It is known that nephrotic syndrome rarely accompanies myeloperoxidase-specific
      antineutrophil cytoplasmic antibody- (MPO-ANCA) related glomerulonephritis. We
      present a case of younger onset MPO-ANCA-related glomerulonephritis accompanied
      with nephrotic syndrome in a female patient. It was diagnosed through the renal
      biopsy and the detection of a high titer of MPO-ANCA and steroid therapy
      (intravenous steroid pulse therapy and oral administration), anticoagulant
      therapy and antiplatelet therapy were initiated. Since her nephrotic syndrome
      persisted in spite of the decrease of MPO-ANCA, we conducted a second renal
      biopsy. We found active necrotizing crescentic glomerulonephritis with a small
      deposition of immunoglobulin and fibrinogen on the glomeruli. To suppress her
      disease activity, we administered second steroid-pulse therapy and MPO-ANCA titer
      disappeared. However, as her nephrotic syndrome, which was accompanied by severe
      hyperlipidemia, persisted, we tried to treat her using low-density lipoprotein
      (LDL) apheresis. It was effective temporarily, but she finally fell into end
      stage renal failure. We discuss here the possibility of double nephropathy by
      considering her clinical and renal pathologic features.

PMID- 14579944
TI  - Membranoproliferative glomerulonephritis associated with hereditary deficiency of
      the 4th component of complement.
AB  - A 10-year-old female patient was found positive for urine protein and occult
      blood on Japanese school urinary screening. Examination of the blood was normal
      except low values of the complement system with CH50 13.5 U/ml, C3 45 mg/dl and
      C4 3 mg/dl. Renal biopsy demonstrated a focal membranoproliferative
      glomerulonephritis (MPGN). As for the activity of each component of the
      complement in the early stage of the disease, the C4 activity was markedly
      declined and the activity of classical pathway component was also decreased, but
      the activity of alternative pathway component was normal. On the HLA examination,
      the patient demonstrated a C4 double null haplotype (C4A2, Q0, BQ0 phenotype). A
      null C4 gene at both the C4A and C4B loci was found in her mother, aunt and
      grandfather on the mother's side and C4B null allele in her father and her
      grandmother on the mother's side. The development of the disease is found in 1
      case and not in the other, although both have the genetic defect and the
      mechanism by which the complement is activated remains unknown. Thus, there
      appear to be many subjects to be studied as to the relationship between the
      defect of C4 gene and immune competence.

PMID- 14579945
TI  - Amyloid A-type renal amyloidosis in a patient with sarcoidosis: report of a case
      and review of the literature.
AB  - A 53-year-old man developed chronic renal failure during a protracted course of
      sarcoidosis. A renal biopsy showed Congo red-positive homogenous deposits in the
      subendothelial space of glomerular capillary walls and arterial walls. On
      electron microscopy, amyloid fibrils were observed in the deposits.
      Immunohistochemistry showed positive staining for amyloid A (AA) protein.
      Treatment with prednisolone resulted in poor response, followed by progressive
      deterioration of renal function requiring hemodialysis. To our knowledge, there
      are 5 cases with histologically proven renal amyloidosis accompanied by
      sarcoidosis. Prognosis in these patients is extremely poor. AA-type amyloidosis
      should be considered as a rare renal complication in the setting of long-standing
      sarcoidosis.

PMID- 14579946
TI  - A renal transplant recipient with pulmonary tuberculosis and visceral
      leishmaniasis: review of superimposed infections and therapy approaches.
AB  - Visceral leishmaniasis (VL) is an acute or subacute disease that is almost
      invariably fatal if untreated. It is a rare disease in renal transplant
      recipients and frequently reported together with other infectious agents. A 39
      year-old renal transplant patient was admitted to hospital for elective coronary
      surgery. In the post-operative period, he developed spiking fever and non
      productive cough and his general condition deteriorated. While he was taking
      medication for non-specific pneumonia, a cavitary lesion occurred in his lung,
      and he had the diagnosis of pulmonary tuberculosis and antituberculous treatment
      was started. Despite treatment, his fever continued. As the patient developed
      pancytopenia and splenomegaly, a bone marrow aspiration was done. Evaluation of
      bone marrow aspirate indicated Leishmania parasites. He was successfully treated
      with a more intensive liposomal amphotericin (L-AmB). Complete cure was achieved
      during follow-up period of 10 months without clinical relapse. In the existence
      of fever and long-standing pancytopenia, VL should be suspected although the
      patient had another proved infection and did not live or visit an endemic area. L
      AmB usage can be safely preferred for treatment of selected renal transplant
      recipients with VL as first-line therapy.

PMID- 14579947
TI  - Acute renal failure after administration of a single dose of a highly selective
      COX-2 inhibitor.

PMID- 14579948
TI  - A case of rhabdomyolysis accompanying acute renal failure secondary to weight
      lifting.

PMID- 14579949
TI  - Posterior leukoencephalopathy with cyclosporine.

PMID- 14579950
TI  - Building a foundation for written communication skills.

PMID- 14579951
TI  - Resonance frequency measurement of implant stability in vivo on implants with a
      sandblasted and acid-etched surface.
AB  - PURPOSE: To determine the changes in stability as a reflection of early healing
      around single-stage, roughened-surface implants in humans utilizing resonance
      frequency analysis (RFA). RFA makes use of a transducer, attached to an implant,
      which is excited over a range of sound frequencies with subsequent response
      analysis. MATERIALS AND METHODS: Twenty patients had 1 to 4 implants placed in
      the posterior maxilla or mandible. Bone type was classified into 1 of 4 groups
      according to the Lekholm and Zarb index (1985). RFA was used for direct
      measurement of implant stability on the day of implant placement and
      consecutively once per week for 6 weeks and at weeks 8 and 10. RESULTS: Twenty
      seven ITI SLA implants placed in the premolar and molar regions of the maxilla
      and mandible were evaluated. Early failure occurred with 1 implant related to
      parafunction. The remaining 26 implants were distributed as follows: 29.6% in
      Type 1 bone, 37% in Type 2 or 3 bone, and 33.3% in Type 4 bone. The lowest mean
      stability measurement was at 3 weeks for all bone types. The percentage decrease
      in stability from baseline to 3 weeks was highest for Type 4 bone (8.6%), as was
      the percentage increase in stability from 3 to 10 weeks (26.9%). A Bonferroni
      adjusted Student t test comparison of bone groups at each time point revealed
      highly significant differences between implant stability in Types 1 and 4 bone at
      3 weeks (P = .004) and a moderately significant difference between Types 2, 3,
      and 4 bone (P = .08) at 3 weeks. Implant stability did not change significantly
      during the 10-week period in Type 1 bone (P > .10). With the same test, by 5
      weeks, no bone groups showed any difference in implant RFA measurements (P =
      1.0). DISCUSSION: This study demonstrated the lowest values for implant stability
      at 3 weeks after placement for all bone types. This effect was statistically
      significant and most pronounced in Type 4 bone. CONCLUSION: There was no
      significant difference in the pattern of stability changes among different bone
      types after 5 weeks of healing.

PMID- 14579952
TI  - Evaluation of the precision of fit between the Procera custom abutment and
      various implant systems.
AB  - PURPOSE: It has been suggested that the CAD/CAM Procera custom abutment may be
      universally applied with multiple implant systems. An acceptable fit between the
      internal hexagon of an abutment and the external hexagon of various implant
      systems, along with true interchangeability of the Procera abutment screw, would
      support this concept. This study determined the precision of fit of the CAD/CAM
      produced Procera abutment onto the external hexagon and bearing surfaces of
      implants from 6 implant manufacturers and the interchangeability of the Procera
      abutment screw with these systems. MATERIALS AND METHODS: This investigation
      consisted of 3 parts: (1) direct measurement of the internal hexagon and bearing
      surface of each Procera abutment and the external hexagon and the bearing surface
      of 6 implants from 6 different systems, (2) radiographic examination of 30
      Procera abutment-implant junctions following tightening to 32 Ncm to determine
      the precision of fit between the bearing surfaces and the top of the external
      hexagon of the implant with the superior surface of the internal hexagon of the
      abutment, and (3) examination of 3 abutment screws and 3 implants from the
      various manufacturers for interchangeability based on American National
      Standards. RESULTS: The mean flat-to-flat external hexagons of the implants
      measured between 2.67 and 2.69 mm. The Procera abutment's flat-to-flat internal
      hexagon measured 2.73 mm. The height of the various implant systems' external
      hexagon ranged from 0.69 to 0.81 mm. The height of the Procera abutment blanks
      was 0.90 mm. Radiographic examination demonstrated that not all of the
      manufacturers' screws fit appropriately within the internal screw bore of the
      Procera abutment. The internal bore of all implant systems studied had a metric
      thread designation of M2 x 0.4 - 6H. The metric thread designation of all
      abutment screws examined was M2 x 0.4 - 6g. The greatest variations in the
      dimensions of the abutment screws measured were seen in the diameter of the screw
      head, which ranged from 2.12 to 2.69 mm. DISCUSSION: The Procera abutment's
      internal hexagon fit the external hexagon of all implant systems evaluated. The
      Procera abutment screw fit the internal screw bore of the implant systems tested.
      CONCLUSION: The Procera abutment with its screw can be universally applied to the
      implant systems studied. This fact, plus the CAD/CAM feature of this system,
      would thus provide a dynamic approach to satisfying the design and spatial needs
      of implant placements observed clinically.

PMID- 14579953
TI  - Early loading of nonsubmerged titanium implants with a sandblasted and acid
      etched (SLA) surface: 3-year results of a prospective study in partially
      edentulous patients.
AB  - PURPOSE: The aim of this study was to evaluate the success rate of ITI implants
      with the SLA surface that were loaded after 6 weeks of healing. MATERIALS AND
      METHODS: In this prospective cohort study, a total of 104 implants were placed in
      posterior sites of 51 partially edentulous patients exhibiting bone densities of
      Class 1, 2, or 3. After a healing period of 6 weeks, all implants were
      functionally loaded with cemented crowns or fixed partial dentures. The patients
      were recalled at 3, 12, 24, and 36 months for clinical and radiographic
      examination. RESULTS: One implant failed to integrate during healing, and 1
      implant was lost to follow-up and considered a dropout. The remaining 102
      implants showed favorable clinical and radiographic findings and were considered
      successfully integrated at the 3-year examination. This resulted in a 3-year
      success rate of 99.03%. DISCUSSION: The peri-implant soft tissues were stable
      over time, as evidenced by no changes in the mean probing depths and the mean
      attachment levels during the follow-up period. None of the radiographs exhibited
      signs of continuous peri-implant radiolucency, which confirmed ankylotic
      stability of all 102 implants. The radiographic evaluation of the bone level at
      the implant indicated stability of the bone crest levels. CONCLUSION: The results
      of this prospective study demonstrated that early loading of ITI implants with
      the SLA surface after an unloaded healing period of 6 weeks provided successful
      tissue integration with high predictability, and that successful tissue
      integration was well maintained up to 3 years of follow-up in this study
      population.

PMID- 14579954
TI  - Load transfer by an implant in a sinus-grafted maxillary model.
AB  - PURPOSE: This in vitro study determined the stress distribution around an implant
      placed in a posterior edentulous maxillary model with simulated sinus grafts that
      had different degrees of stiffness. MATERIALS AND METHODS: The composite
      photoelastic model with a standard threaded implant consisted of simulated
      crestal cortical, cancellous, sinus cortical, and grafted bone. The graft
      maturation process and inherent graft quality were represented in the model by
      varying the stiffness of the graft. Prior to placement of the simulated graft,
      axial and inclined loads were applied to the implant The stresses that developed
      in the supporting structures were analyzed photoelastically. The graft was then
      placed and the testing procedure was repeated over 4 consecutive days, during
      which time the simulated graft stiffened. RESULTS: The stress analysis indicated
      that before placement of the simulated graft, loading on the implant transferred
      the highest stresses to cortical bone. The presence of the simulated graft
      transferred stress from the native bone simulants to the simulated grafted bone.
      DISCUSSION: As the stiffness of the graft increased, a more equitable stress
      distribution was observed in the multilayer bone surrounding the implant.
      CONCLUSION: Loading of an implant in a less stiff grafted sinus could lead to
      overloading of the native bone as well as the maturing grafted bone.

PMID- 14579955
TI  - Three-dimensional finite element stress analysis of a cuneiform-geometry implant.
AB  - PURPOSE: The biomechanical behavior of an osseointegrated dental implant plays an
      important role in its functional longevity inside the bone. Studies of this
      aspect of dental implants by the finite element method are ongoing. In the
      present study, a cuneiform-geometry implant was considered with a 3-dimensional
      model that had a mesh that was finer than in the models commonly found in the
      literature. MATERIALS AND METHODS: A mechanical model of an edentulous mandible
      was generated from computerized tomography, with the implant placed in the left
      first premolar region. A 100-N axial load was applied at the implant abutment,
      and the mandibular boundary conditions were modeled considering the real geometry
      of its muscle supporting system. The cortical and trabecular bone was assumed to
      be homogeneous, isotropic, and linearly elastic. RESULTS: The stress analysis
      provided results that were used to plot global and detailed graphics of normal
      maximum (S1), minimum (S3), and von Mises stress fields. The results obtained
      were analyzed and compared qualitatively with the literature. DISCUSSION:
      Quantitative comparisons were not performed because of basic differences between
      the model adopted here and those used by other authors. The stress distribution
      pattern for the studied geometry was similar to those found in the current
      literature, but insignificant apical stress concentration occurred. The stress
      concentration occurred at the neck of the implant, ie, in the cortical bone,
      which was similar to results for other implant shapes reported in the literature.
      CONCLUSION: The studied geometry showed a smooth stress pattern, with stress
      concentrated in the cervical region. The values, however, were within the range
      of values found in the cortical layer far from the implant, caused by the
      muscular action. No significant stress concentration was found in the apical
      area.

PMID- 14579956
TI  - Enhanced bone-to-implant contact by platelet-released growth factors in
      mandibular cortical bone: a histomorphometric study in minipigs.
AB  - PURPOSE: To determine the effects of platelet-released growth factors (PRGF) on
      bone-to-implant contact (BIC) in minipig cortical bone. MATERIALS AND METHODS: In
      each of 8 adult minipigs, 2 implants were placed in the facial wall of the
      mandible, one implant with and one without PRGF. PRGF was defined as the
      supernatant from washed, thrombin-activated, allogenic, platelet-rich plasma
      cells obtained after centrifugation. Four animals were sacrificed at 4 weeks, and
      the remaining 4 were sacrificed at 8 weeks. For histomorphometric analyses,
      undecalcified ground specimens were prepared and stained with the Levai-Laczko
      stain. RESULTS: For the entire follow-up time, 55.30% BIC was found with PRGF
      versus 38.91% without PRGF (P = .0198). At 4 weeks, BIC was 44.20% with PRGF
      versus 29.62% without PRGF (P = .0632), and at 8 weeks there was 70.36% BIC with
      PRGF versus 48.20% without PRGF (P = .1221). DISCUSSION: Growth factors and other
      molecules released upon activation of platelet-rich plasma cells can enhance
      implant anchorage in cortical bone. PRGF obtained from allogenic sources does not
      impair healing. CONCLUSION: The results indicated that a single application of
      PRGF before implant placement can be sufficient to increase the percent BIC in
      minipig cortical bone.

PMID- 14579957
TI  - Porous hydroxyapatite for grafting the maxillary sinus in sheep: comparative
      pullout study of dental implants.
AB  - PURPOSE: In this experimental study, dental implants placed after maxillary sinus
      grafting with either porous hydroxyapatite (HA) (Interpore 200) or autogenous
      bone were examined for their mechanical stress tolerance. MATERIALS AND METHODS:
      A total of 54 titanium plasma flame-sprayed cylindric implants were placed in the
      lateral sinus wall bilaterally of 27 mountain sheep. The bony sinuses were opened
      through an extraoral approach. Eighteen sinuses were grafted with porous HA, and
      another 18 were grafted with cancellous bone from the iliac crest. Eighteen non
      grafted sinuses were used as controls. In the same operation, 2 cylindric
      implants were placed in each of the sinuses. One implant of each sinus was tested
      for mechanical strength of the bone-implant interface at 12, 16, and 26 weeks
      using pullout force. RESULTS: The mean pullout force was 259.3 N in the control
      group, 356.7 N in the autogenous bone group, and 376 N in the HA group. Pooled
      data for the grafted sites showed the pullout force to be significantly higher
      than in the empty control sites (P = .02). The pullout force increased
      significantly with ongoing healing time (P = .02), but there was considerable
      variation within the groups. While the force remained more or less constant
      throughout the follow-up time in the controls (248 N at week 12 to 276 N at week
      26), it increased dramatically in the group augmented with autogenous bone (223.8
      N at week 12 to 523.16 N at week 26). The pullout force was initially highest in
      the HA group (302.3 N at week 12) and increased to 423.5 N at 26 weeks, but it
      did not reach the levels recorded in the autografted group. DISCUSSION AND
      CONCLUSION: Mechanical tests of bone-to-implant contact in a sheep model showed
      that HA for 1-stage sinus floor elevation significantly increased the pullout
      force versus ungrafted sinuses, although it was less than that found with
      autogenous bone after 26 weeks.

PMID- 14579958
TI  - Methods for comparing the results of different studies.
AB  - The reader of oral and maxillofacial implant literature is challenged to be
      cognizant of the quality of clinical research data. The large variety of possible
      study designs utilized by clinical researchers requires the reader to have a
      fundamental awareness of the advantages, disadvantages, and limitations of
      commonly utilized study designs. This article aims to provide the reader with
      information to make an informed decision regarding the quality of a clinical
      research paper, so that he or she can judge whether the information presented in
      any given manuscript was obtained in a manner that truly minimizes bias, in the
      form of systematic or random errors, and whether it warrants serious
      consideration for clinical decision making. Special consideration is given to
      scientific literature pertaining to the use of oral and maxillofacial implants.
      In addition, the reader is presented with a method for placing any single
      manuscript within a "hierarchy of evidence" enabling an "estimate of confidence"
      in a particular therapy. By utilizing such methods to appraise the quality of
      research data, clinicians and patients will be better informed when making
      treatment-planning decisions.

PMID- 14579960
TI  - Robot-assisted placement of craniofacial implants.
AB  - PURPOSE: The purpose of this study was to improve and accelerate the
      rehabilitation process for patients with severe ear microtia with an implant
      anchored auricular prosthesis. A medically approved robot system was used to
      place the craniofacial implants and a new process was developed for preoperative
      fabrication of the prosthesis using a rapid prototyping technique. MATERIALS AND
      METHODS: Preoperatively, after computerized tomography, the implant positions
      were determined in a planning tool according to bone availability and esthetic
      considerations. Intraoperatively, the robot showed the surgeon the planned
      implant positions and guided the placement procedure. RESULTS: The accuracy
      measurements showed that with this robot system, absolute implant position
      accuracy of approximately -0.5 +/- 0.4 mm, a relative accuracy between the
      implants of approximately 0.2 +/- 0.5 mm, and a deviation from the parallel
      position of approximately 0.6 +/- 0.5 degrees were achieved. Thirty implants were
      placed in 13 patients with robot assistance with no intraoperative injuries.
      DISCUSSION: This technique made it possible to apply the preoperatively
      fabricated auricular prosthesis directly after surgery. CONCLUSION: From this
      experience it can be concluded that the robot system and the new manufacturing
      concept for anaplastology can be applied advantageously in other areas of the
      head as well.

PMID- 14579961
TI  - Cement-retained versus screw-retained implant restorations: a critical review.
AB  - This article presents a comparison of screw-retained and cement-retained implant
      prostheses based on the literature. The advantages, disadvantages, and
      limitations of the 2 different types of restorations are discussed, because it is
      important to understand the influence of the attachment mechanism on many
      clinical aspects of implant dentistry. Several factors essential to the long-term
      success of any implant prosthesis were reviewed with regard to both methods of
      fixation. These factors include: (1) ease of fabrication and cost, (2) passivity
      of the framework, (3) retention, (4) occlusion, (5) esthetics, (6) delivery, and
      (7) retrievability. (More than 50 references).

PMID- 14579959
TI  - Antimicrobial efficacy of semiconductor laser irradiation on implant surfaces.
AB  - PURPOSE: This study was conducted to investigate the antimicrobial effect of an
      809-nm semiconductor laser on common dental implant surfaces. MATERIALS AND
      METHODS: Sandblasted and acid-etched (SA), plasma-sprayed (TPS), and
      hydroxyapatite-coated (HA) titanium disks were incubated with a suspension of S.
      sanguinis (ATCC 10556) and subsequently irradiated with a gallium-aluminum
      arsenide (GaAlAs) laser using a 600-microm optical fiber with a power output of
      0.5 to 2.5 W, corresponding to power densities of 176.9 to 884.6 W/cm2. Bacterial
      reduction was calculated by counting colony-forming units on blood agar plates.
      Cell numbers were compared to untreated control samples and to samples treated
      with chlorhexidine digluconate (CHX). Heat development during irradiation of the
      implants placed in bone blocks was visualized by means of shortwave thermography.
      RESULTS: In TPS and SA specimens, laser irradiation led to a significant
      bacterial reduction at all power settings. In an energy-dependent manner, the
      number of viable bacteria was reduced by 45.0% to 99.4% in TPS specimens and
      57.6% to 99.9% in SA specimens. On HA-coated disks, a significant bacterial kill
      was achieved at 2.0 W (98.2%) and 2.5 W (99.3%) only (t test, P < .05). For
      specimens treated with CHX, the bacterial counts were reduced by 99.99% in TPS
      and HA-coated samples and by 99.89% in SA samples. DISCUSSION: The results of the
      study indicate that the 809-nm semiconductor laser is capable of decontaminating
      implant surfaces. Surface characteristics determine the necessary power density
      to achieve a sufficient bactericidal effect. The bactericidal effect, however,
      was lower than that achieved by a 1-minute treatment with 0.2% CHX. The rapid
      heat generation during laser irradiation requires special consideration of
      thermal damage to adjacent tissues. CONCLUSION: No obvious advantage of
      semiconductor laser treatment over conventional methods of disinfection could be
      detected in vitro.

PMID- 14579962
TI  - Preliminary 3-dimensional surface texture measurement and early loading results
      with a microtextured implant surface.
AB  - PURPOSE: This investigation was conducted to obtain preliminary roughness data on
      a microtextured implant surface and to determine its ability to sustain a 1-stage
      surgical procedure and early full occlusal loading of single-tooth restorations
      in humans. MATERIALS AND METHODS: Three-dimensional (3D) vertical scanning
      interferometry was conducted on samples of the test surface (MTX) and 2 control
      surfaces (Osseotite and sandblasted/acid-etched [SLA]). Test implants were also
      placed in vivo, restored with fully occluding single-tooth restorations (n = 27)
      after 2 months of nonsubmerged healing, and clinically monitored for 48 months of
      follow-up. RESULTS: Microtexture was relatively uniform on the test surface and
      more random and irregular on the control surfaces. MTX and Osseotite were similar
      in some roughness parameters, but the MTX surface had a greater number of
      micropits that were spaced closer together (Stylus Y lambda q) and with higher
      slope values (Stylus Y delta q). Cumulative life table results were 100% for all
      MTX implants placed in maxillary and mandibular jaw locations, and no discernible
      marginal bone changes were observed. Overall implant success was 100% after 4
      years of clinical functioning. DISCUSSION: The findings of this study appear
      promising but should be considered preliminary, because of the limitations in the
      number of locations measured on each product sample and the small number of
      implants clinically studied. CONCLUSION: Within the scope of the present study,
      MTX implants exhibited a uniform micropitted surface, as well as 100% survival
      and 100% clinical success after nonsubmerged placement, early loading with single
      tooth restorations at 2 months, and 48 months of clinical functioning. (More than
      50 references.)

PMID- 14579963
TI  - Nonsurgical management of bilateral mandibular fractures associated with dental
      implants: report of a case.
AB  - A case is presented in which bilateral fractures of the mandible occurred
      following placement of endosseous dental implants. The management, with
      approximately 7 years of follow-up, is described and the potential causes of such
      fractures and their treatment are discussed.

PMID- 14579964
TI  - Treatment for an endosseous implant migrated into the maxillary sinus not causing
      maxillary sinusitis: case report.
AB  - Placement of endosseous implants in the maxilla has been proven to be a reliable
      treatment modality. If there is lack of supporting bone, the placed implant may
      not have enough primary stability and may migrate into the maxillary sinus.
      Displaced implants must be removed. If there are no signs of maxillary sinusitis,
      augmentation of the resulting alveolar defect can be performed during the same
      procedure.

PMID- 14579965
TI  - Tissue engineering: modifying the healing response.

PMID- 14579966
TI  - Gingival esthetics for immediately restored dental implants: prosthodontic and
      surgical procedures.

PMID- 14579967
TI  - Implants in the atrophic partially edentulous maxilla. Single tooth gaps vs
      extended edentulous spaces.

PMID- 14579968
TI  - Achieving optimal esthetics in the atrophic, partially edentulous maxilla-single
      tooth and segmental restorations.

PMID- 14579969
TI  - Maxillary anterior implants--recipes for restoration success.

PMID- 14579970
TI  - Restorative considerations in the treatment of the atrophic posterior mandible.

PMID- 14579971
TI  - Treatment of the atrophic mandibular ridge.

PMID- 14579972
TI  - Atrophic posterior mandibular reconstruction utilizing mandibular block
      autografts: risk management.

PMID- 14579973
TI  - Implant prosthodontic and restorative complications--predictors, prevention, and
      management.

PMID- 14579975
TI  - Soft tissue complications--the esthetic dilemma.

PMID- 14579974
TI  - Implant prosthodontic and restorative complications.

PMID- 14579977
TI  - Management of complications: bone grafting and augmentation.

PMID- 14579976
TI  - Complications of hard tissue grafting for implant placement.

PMID- 14579978
TI  - Implants--legal and liability issues.

PMID- 14579979
TI  - Rehabilitation and osseointegration in clinical reality.

PMID- 14579980
TI  - Study on efficacy of WHO-ORS in malnourished children with acute dehydrating
      diarrhoea.
AB  - Twenty-five well nourished children (group A) and 25 malnourished children (group
      B) of acute diarrhoea with some dehydration were taken up for the study. Both the
      groups were given World Health Organisation-oral rehydration solution (WHO-ORS)
      as per WHO guidelines. In both the groups, isonatraemic dehydration was the
      commonest (group A 64%, group B 56%). Hypokalaemia was noted in 32% cases in
      group A and 60% cases in group B. Oral rehydration therapy (ORT) was successful
      in 92% cases in well nourished group A cases and in 80% in group B cases. The
      mean time in hours required for hydration (group A 8.1+/-1.6; group B 9.1+/-1.4;
      p<0.05) and hospital stay in days (group A 1.6+/-0.9; group B 3.2+/-3.3; p<0.05)
      were longer in group B.

PMID- 14579981
TI  - Efficacy of oral rehydration therapy in dehydrating diarrhoea of children.
AB  - Establishment of diarrhoea treatment and training units (DTTUs) in all major
      health facilities for promotion of appropriate oral rehydration therapy (ORT) is
      an important strategy for control of diarrhoeal diseases (CDD) in children in
      this country. Univariate analysis of mortality experiences of a random sample of
      225 diarrhoea cases among children treated at DTTU in the department of
      paediatric medicine, RG Kar Medical College, Kolkata revealed that case fatality
      rate (CFR) of diarrhoea was much higher among children treated with parenteral
      fluid therapy with or without drugs (20.6% and 20.9% respectively), compared to
      those treated with oral rehydration solution (ORS) only (0.75%). Certain child
      care practices, like immunisation, breastfeeding and use of ORS at home also
      favourably influenced survival of children suffering from diarrhoea. The CFR of
      diarrhoea cases did not depend on type of diarrhoea or nutritional status of the
      child. Thus, promotion of correct practice of ORT merits attention through all
      possible means.

PMID- 14579982
TI  - History of the development of oral rehydration fluids.
AB  - The development of oral rehydration fluid for the treatment of cholera and other
      diarrhoeal diseases has been regarded as one of the most important medical
      advances of the last century. This article summarises information on how this
      achievement was made possible. The development is traced from the historical
      empiric use of oral fluids for treating diarrhoea, to physiologic studies in
      animals that defined how glucose and sodium were coupled in absorption by the
      small intestine and finally, to the use of this knowledge in developing the
      simple effective solutions that were adopted by WHO as the mainstay of diarrhoeal
      therapy worldwide.

PMID- 14579983
TI  - Evolution in the recommendations for oral rehydration therapy according to World
      Health Organisation guidelines: where to go from here?
AB  - Guidelines on the use of oral rehydration salts (ORS) have been revised over the
      years based on evidence from research studies and clinical experience. This paper
      charts the evolution in oral rehydration therapy (ORT) in the context of World
      Health Organisation (WHO) recommendations. Diarrhoeal disease case management,
      with ORT as its cornerstone, has had tremendous success in terms of
      implementation and outcome. To further decrease global diarrhoeal morbidity and
      mortality, there should be increased efforts to accelerate the introduction of
      safe, effective, and affordable against diarrhoeal pathogens such as cholera and
      rotavirus.

PMID- 14579984
TI  - Oral rehydration therapy with particular reference to super ORS.
AB  - An improved solution of glucose and three salts (ORS) is an elegant and
      deceptively simple treatment technology to prevent or treat dehydration from
      diarrhoea. There are many types of formulation tested earlier. First generation
      improved ORS trials, cereal-based ORS formulations, rice-based ORS trials,
      glucose-ORS with reduced osmolarity are summarised in the article to have a look
      of every pros and cons of oral rehydration therapy (ORT). Since the adoption of
      ORT, estimates of deaths due to diarrhoea in children below 5 years of age have
      fallen dramatically from 4.6 million in 1980 to 1.8 million in the year 2000.

PMID- 14579985
TI  - Future challenges in communication for promoting ORT--an overview.
AB  - Oral rehydration therapy (ORT) is a cheap and simple intervention aimed to
      prevent mortality and morbidity associated with dehydration due to diarrhoea. ORT
      promotion strategies through programme communication, social mobilisation and
      social marketing, and advocacy efforts have yielded substantial improvement in
      the scenario. However, it has also taught us lessons and suggested changes in
      communication strategies to make the promotion efforts more effective in future.

PMID- 14579986
TI  - Role of oral rehydration therapy in controlling epidemic of cholera and watery
      diarrhoea.
AB  - Oral rehydration therapy (ORT) is basically oral administration of liquid
      containing various electrolytes in specific proportions to prevent and treat
      dehydration. This treatment facilitates safe and optimal absorption of water and
      essential electrolytes such as sodium chloride, sodium bicarbonate and potassium
      chloride in dehydrated patients. Successful ORT was experienced in cholera
      patients in Kolkata and Dhaka which was followed by the development of oral
      rehydration salt (ORS). This procedure can be safely implemented at home. ORT
      reduced mortality rate both in cholera and non-cholera watery diarrhoea. The
      various health authorities must support preparedness before pre-positioning of
      adequate stocks of ORS packets for emergency situations. Health workers should
      have been the knowledge to prepare ORS solutions.

PMID- 14579987
TI  - Current perspectives on statins.
AB  - As the epidemic of coronary artery disease rages on round the globe, research is
      always on to find suitable drugs to reverse the trend. While aspirin, beta
      blockers and ACE inhibitors have been shown to reduce coronary mortality and
      morbidity, statins are rapidly coming to fore as another important cog in the
      wheel of primary and secondary prevention of coronary artery disease. Newer trial
      like Heart Protection Study suggests benefit of statin for high risk individuals,
      irrespective of initial serum cholesterol concentrations. This may be of great
      relevance in the Indian context taking into consideration the vast majority of
      coronary artery disease patients having normal to mildly elevated serum
      cholesterol in contrast to their western counterparts.

PMID- 14579988
TI  - Heterotransplantation of kidney: medical and legal issues.
AB  - Since 1905, various attempts were made to transplant kidney from rabbit, pig or
      goat. But the attempts failed due to strong immune reaction-response.
      Heterotransplantation or xenotransplantation is a process to transplant kidney
      between various species. Allotransplantation is costly and needs lifelong
      immunosuppression associated with high risk rate of infection and other
      complications. Moreover legal and social issues involved in the process should be
      taken into account. So xenotransplantation is definitely an improved process.

PMID- 14579989
TI  - Efficacy and tolerability of itopride hydrochloride in patients with non-ulcer
      dyspepsia.
AB  - To document the clinical efficacy and tolerability of itopride hydrochloride in
      patients with non-ulcer dyspepsia an open-label, non-comparative study, was
      undertaken at the Medical College, Thiruvananthapuram, among patients with
      endoscopically confirmed diagnosis of non-ulcer dyspepsia or chronic gastritis.
      Itopride hydrochloride 50 mg (1 tablet) thrice a day for 2 weeks was administered
      among them. Relief of symptoms at the end of two weeks treatment, assessed as
      marked/complete, moderate, slight, none or worse; QT interval on ECG; adverse
      events; haemogram; serum chemistry for hepatic and renal functions. None had QT
      prolongation on ECG. At the end of 2 weeks' treatment, moderate to complete
      relief of symptoms was reported by 22 patients (73%), whereas 5 (17%) reproted
      slight improvement, and 3 (10%) reported no improvement. Clinical tolerability
      was excellent in 28 patients (93%) and good in 2 (7%). None of the patients had
      any prolongation of QT on ECG, nor did any patient show any abnormality in
      haemogram or serum chemistry during the treatment.

PMID- 14579990
TI  - Management of the acute exacerbation of asthma.
AB  - All patients with asthma are at risk of having asthma exacerbations characterized
      by worsening symptoms, airflow obstruction, and an increased requirement for
      rescue bronchodilators. The goals of managing an asthma exacerbation are prompt
      recognition and rapid reversal of airflow obstruction to avert relapses and
      future episodes. Short-acting beta-agonists, oxygen, and corticosteroids form the
      basis of management of acute asthma exacerbation, but a role is emerging for
      anticholinergics and newer agents such as levalbuterol and formoterol. Initiation
      or intensification of long-term controller therapy, treatment of comorbid
      conditions, avoidance of likely triggers, and timely follow-up care prevent
      setbacks. Acceptance of current treatment guidelines by physicians and adherence
      to the recommended clinical regimens by patients are essential for effective
      management of asthma. The physician should strive to establish a constructive
      relationship with the patient by addressing the patient's concerns, reaching
      agreement on the goals of therapy, and developing a written action plan for
      patient self-management.

PMID- 14579991
TI  - Environmental management of asthma at top-ranked U.S. managed care organizations.
AB  - We evaluated the status of nationally top-ranked managed care organizations'
      (MCOs) asthma disease management programs to identify "best practices" in the
      environmental treatment and control of asthma. Application materials were
      developed and mailed to the top 34 managed care organizations, as determined by
      the ranked results from the October 1998 edition of US News and World Report.
      Based on the results of a staff and panel review, five applicants were selected
      for site visitation. The results of the site visits determined two finalists and
      three runners-up. We recommend that MCOs integrate population and community-based
      strategies and seek an emphasis on prevention. We encourage collaborations with
      other organizations and agencies. We endorse home visitation to assess
      environmental factors and also support use of telephonic case management. We
      think that smoking cessation programs should be coordinated with asthma
      management. We consider it important to use alternative forms of communication
      such as the Internet. And we find that it is important to be mindful of language,
      culture, and literacy.

PMID- 14579992
TI  - The impact of exacerbations on the asthmatic patient's preference scores.
AB  - The purpose of this study was to examine the effect of exacerbations on mild to
      moderate asthmatic patients' preference-based, health-related, quality of life
      scores and also to describe the effect of these exacerbations on daily life. In a
      survey, 100 mild to moderate asthmatic patients in the United Kingdom were asked
      to rate three different health marker states on a scale between 0 (death) and 100
      (perfect health), defined as: your asthma of today, a mild exacerbation, and a
      severe exacerbation of asthma. They were also asked to describe their symptoms
      and what they did when experiencing an exacerbation. During exacerbations the
      vast majority of asthmatic patients have significant symptoms and consume a
      considerable amount of health care resources, which often overlap. The health
      marker state "your asthma of today" was given a mean score of 81.0, a mild
      exacerbation a score of 62.1, and a severe exacerbation a score of 25.6,
      indicating a large impact on patients' daily life and their health-related
      quality of life. In conclusion, asthmatic patients are severely affected in their
      health and daily living by mild and severe exacerbations. Considerable effort
      should be made to reduce the number and severity of exacerbations.

PMID- 14579993
TI  - Effect of high starting dose of budesonide inhalation suspension on serum
      cortisol concentration in young children with recurrent wheezing episodes.
AB  - INTRODUCTION: There are no available data on the safety of recommended schedules
      for the initiation of treatment with budesonide inhalation suspension in children
      with recurrent wheezing episodes. We compared the safety of high and low starting
      dose of budesonide by measuring their effect on plasma cortisol concentration.
      METHODS: A randomized double-blind, placebo-controlled design was used. Twenty
      nine children ages 6 months to 3 years were divided into three groups: (1) high
      starting dose: 1 mg budesonide inhalation suspension twice daily followed by a
      stepwise decrease of 25% every second day for 8 days (n = 11); (2) low starting
      dose: 0.25 mg twice daily for 8 days (n = 11); (3) placebo (n = 7). The 8 AM
      (fasting) and 1-hour post-ACTH stimulation plasma cortisol concentrations were
      measured before and 10 days after initiation of budesonide treatment. RESULTS:
      Before treatment and after 8-10 days of treatment, there was no significant
      difference in mean serum cortisol concentration in the high starting dose, low
      dose and placebo groups, either at 8 AM or at 1 hour after ACTH stimulation.
      CONCLUSION: The administration of nebulized suspension of budesonide at a high
      starting dose (2 mg/day for 2 days) followed by a rapid stepwise decrease over 8
      days was safe, causing similar changes in serum cortisol levels to low-dose
      budesonide suspension or placebo.

PMID- 14579994
TI  - Evaluation of self-management education for asthmatic patients.
AB  - Self-management of asthma, achieved through an effective educational program for
      asthmatic patients, is very important in facilitating adaptation to illness and
      positive response to treatment. An effective self-management plan helps patients
      to gain information about and skills in life style modifications, self
      monitoring, and environmental control. The study, both descriptive and analytic,
      was planned as a means to evaluate the need of asthmatic patients for self
      management education and to design supportive educational programs. The study
      group consisted of 42 adult patients who were chosen randomly from among patients
      treated in the Chest Diseases Department of the Medical Faculty of Istanbul
      University. The following evaluation tools were used: St. George Respiratory
      Questionnaire, a questionnaire designed by the research team, and patients'
      asthma diaries. The survey form designed by the research team included questions
      about demographic characteristics, asthma triggering factors, and morbidity
      factors. An asthma educational program, consisting of one session that lasted for
      120 minutes, was implemented by doctors and nurses in cooperation and, 2 months
      later, patients were followed up. After completion of the educational program, it
      was found that patients related their health during the last month and the extent
      to which they drew benefits from their treatment with higher scores, the result
      clearly stating that the impact of asthma on their lives has experienced a
      decrease. The educational program was thus implemental in improving the quality
      of patients' lives. Results have finally shown that our educational program can
      be used as a model by other health care centers in our country.

PMID- 14579995
TI  - A Cox regression analysis of covariates for asthma hospital readmissions.
AB  - BACKGROUND: Asthma hospital admissions and readmissions are unacceptably high,
      thus, a method to identify those at greatest risk could be helpful. METHODS: An
      observational retrospective study using a Cox regression to determine the
      relationship between the time interval between admissions and possible covariates
      of a readmission. The covariates were age, sex, ethnicity, smoking habit, history
      of allergy or eczema/hay fever, age of onset, Townsend index (TI), Jarman score
      (JS), and drugs on discharge. Those with p < 0.2, together with interacting
      covariates, from the preliminary analysis were eligible for the multivariate Cox
      regression analysis. RESULTS: Of the 523 patients admitted between 1994 and 1998
      because of their asthma, complete data were available for 440. Of these, 112 were
      readmitted. Eligible covariates for the multivariate Cox regression analysis were
      sex, allergy status, history of eczema/hay fever, the JS and TI together with
      interactions between JS and TI, JS and allergy, and allergy with eczema/hay
      fever. There were 278 subjects (71 with a readmission) with complete data for
      these eligible covariates. The multivariate analysis revealed that female sex
      (odds ratio [OR] = 2.65, 95% confidence interval [CI] 1.42, 4.92), high JS (OR =
      2.03, 95% CI 1.13-3.65), and history of allergy (OR = 1.88, 95% CI 1.06-3.32)
      formed the final model as significant predictors of readmission. CONCLUSION:
      Females with a history of allergy that were registered at a practice with a high
      workload (JS) had a higher risk of readmission. The analysis method used
      highlights how those at risk of readmission can be identified so that they can be
      targeted post discharge.

PMID- 14579996
TI  - Exhaled nitric oxide as a simple assessment of airway hyperresponsiveness in
      bronchial asthma and chronic cough patients.
AB  - Exhaled nitric oxide (NO) has been suggested to be a marker of airway
      inflammation. The aim of this study was to evaluate the role of exhaled NO in
      bronchial asthma and chronic cough patients to predict bronchial
      hyperresponsiveness (BHR). We measured the exhaled NO concentration using the
      chemiluminescence method in 52 asthma patients (group I consisting of 24 without
      prior inhaled corticosteroid (ICS) use, and group II consisting of 28 previously
      on ICS and 16 chronic cough patients in group III). In addition to regular
      examinations, spirometry and methacholine inhalation tests using the Astograph
      were done. In group I, a significantly negative correlation was observed
      regarding the exhaled NO concentration with FEV1/FVC%, V50, and BHR that was
      assessed as Dmin and PD35-Grs, and a positive correlation with peripheral blood
      eosinophils. In group III, a significantly negative correlation was seen
      regarding the exhaled NO concentration with BHR. We thus concluded that measuring
      exhaled NO concentration appears to be a useful noninvasive method to predict the
      BHR, airway obstruction, and inflammation in asthma and chronic cough patients.

PMID- 14579997
TI  - Documenting asthma severity: do we get it right?
AB  - BACKGROUND: The 1997 National Asthma Education and Prevention Program (NAEPP)
      recommends a severity classification scheme to optimize the use of anti
      inflammatory therapy for persistent asthma. Physician documentation of asthma
      severity is often used as a quality assurance measure. OBJECTIVE: To test the
      hypothesis that physician documentation of asthma severity is associated with
      appropriate use of anti-inflammatory therapy. DESIGN/METHODS:  SETTING: inner
      city academic health center. First, we reviewed a consecutive sample of charts of
      scheduled pediatric patients. Then, we administered a structured parent survey
      regarding the child's asthma symptoms and current asthma therapy. We used NAEPP
      guidelines to classify patients' severity of asthma. The main outcome measure was
      appropriate use of anti-inflammatory therapy. Appropriate therapy was defined as:
      (1) mild persistent asthmatics using anti-inflammatory therapy, and (2) moderate
      severe persistent asthmatics using inhaled steroids. Chart classification of
      asthma severity was compared with the NAEPP-applied classification. RESULTS: Of
      784 charts, 214 (27%) were asthmatic. Of these, 176 (82%) were surveyed. The mean
      age was 7.4 years; 61% were males. Severity classification was documented in 77%
      of charts. Chart documentation differed significantly from survey classification
      for the same patients: (mild intermittent 54% vs. 40%, mild persistent 21% vs.
      14%, moderate persistent 24% vs. 36%, severe persistent 1% vs. 10%; all p <
      .001). Correctly classified patients were more likely to be on appropriate
      therapy. CONCLUSIONS: Physicians underestimated the severity classification of
      asthmatic patients. Incorrect classification was associated with inappropriate
      asthma therapy. These findings have implications for the institution of asthma
      quality improvement programs.

PMID- 14579998
TI  - Growth of asthmatic children before long-term treatment with inhaled
      corticosteroids.
AB  - The aim of this study was to examine the growth of asthmatic children before any
      long-term inhaled corticosteroid treatment. We studied 436 asthmatic children
      (254 boys and 182 girls), age range 3.9-15.4 years, that had not been treated
      with long-term inhaled corticosteroids. In each child height and weight were
      measured, and the height standard deviation score (HSDS) and the weight for
      height ratio (%WFH) were calculated. We also estimated asthma severity and tested
      atopic status by skin testing. Children were grouped into three age groups:
      prepuberty (3.9-7.9 years), peripuberty (8-11.9 years), and puberty (12-15.5
      years). HSDS was correlated to asthma severity and duration, atopic status, and
      other coexisting allergic diseases. Seven hundred ten healthy children (345 boys,
      365 girls) ages 4.1-15.5 years were used as controls for height and weight. There
      was no statistically significant difference in HSDS and %WFH between patients and
      controls, except for HSDS of pubertal female patients that was significantly less
      than that of controls, x: 0.06 (0.80) vs. x: 0.40 (0.90), respectively, p < 0.02.
      There was also no significant correlation between HSDS or %WFH and severity or
      duration of the disease, allergy status and other coexisting allergic diseases.
      However, there was significant difference in menarcheal age between asthmatic
      girls x: 12.49 (0.12) and controls x: 12.00 (0.10), p < 0.001. In conclusion, our
      data show that the growth of asthmatic children before any long-term treatment
      with inhaled corticosteroids is not different from the control population, except
      for the asthmatic girls of pubertal age who are shorter than control girls
      probably because of delay in pubertal maturation.

PMID- 14579999
TI  - Cost, morbidity, and control of asthma in Hungary: The Hunair Study.
AB  - OBJECTIVE: To assess asthma-related morbidity, symptom control, and societal cost
      of asthmatic patients in Hungary. Secondary objective was to assess the
      relationship between asthma symptom control and costs incurred. METHODS: Three
      hundred seventy-eight pediatric asthma patients (6-14 years of age) and 711 adult
      asthma patients (18-55 years of age) in 19 pulmonary clinics were interviewed by
      their physicians regarding asthma-related drug therapy and recent (past 2 weeks)
      asthma morbidity (daytime asthma symptoms, nocturnal symptoms, limitation in
      daily activities resulting from asthma and asthma exacerbation). Physicians
      estimated patients' level of asthma control based on the Global Initiative of
      Asthma guidelines. Direct and indirect costs for asthma-related resources were
      determined based on patient reported 6 months' data except for drug costs that
      were based on patient reported 2 weeks of data. All cost data were annualized.
      RESULTS: Patients in the study were mostly prescribed inhaled controller
      medications for asthma symptom management (76.2% pediatric and 92.3% adult)
      during the 2 weeks preceding the survey. Asthma-related morbidity was experienced
      by 15% of pediatric patients and 30% of the adult patients at least once during
      the 2 weeks preceding the survey. Physician classified 69% of pediatric patients
      as having good control, 27.5% as having moderate control, and 2.8% as having poor
      control of their asthma. In the adult population, 50.7% were classified as having
      good control, 36.6% as having moderate control, and 12.7% as having poor control.
      The average total annual costs (direct and indirect costs) per patient were 833
      EUR (897 USD) for pediatric patients and 632 EUR (681 USD) for adult patients. In
      both pediatric and adult patients the total costs were highest for patients with
      poor asthma control. The total cost per patient increased in the ratios of 1 to
      1.4 to 2.4 for pediatric patients and 1 to 1.5 to 2.9 for adult patients with
      good, moderate, and poor control of asthma, respectively. CONCLUSION: Inhaled
      corticosteroids was the most frequent treatment prescribed for asthma patients in
      the study. However, patients reported substantial asthma-related morbidity.
      Children used more resources than adults, despite being classified as having
      better control. Patients with poor control of asthma symptoms incurred the
      highest societal cost, improving patient control may reduce cost to society by
      40% or more.

PMID- 14580000
TI  - Characteristics of acute asthma patients attended frequently compared with those
      attended only occasionally in an emergency department.
AB  - Asthma patients that depend on emergency department (ED) services are generally
      considered to have extremely poor disease control and prognosis. It is important
      to identify characteristics related to poor disease control and frequent visits
      to the ED to apply appropriate clinical management. This study comprised a cross
      sectional survey of consecutive patients with asthma exacerbation (age > or = 12
      years) presenting at the adult ED of a large, tertiary care, university
      affiliated hospital over a 2-month period. The frequent visitors (FV) were
      defined by > or = 3 visits to the ED in the preceding year, and the occasional
      visitors (OV) by < or = 2 visits. Eighty-six patients (61 females and 25 males)
      were included in the study (mean age 38 +/- 18 years). Of these patients, 51.2%
      were FV and 48.8% were OV. Sixty-nine percent had annual income lower than A
      dollar 3000 and 66.3% had < or = 8 years of the formal education. Only 18.6% had
      used inhaled corticosteroids, 79.1% identified the asthma attack severity, 70.9%
      increased or initiated inhaled beta-agonist, 20.9% increased or initiated steroid
      therapy, and 55.8% had an asthma action plan for attack. The number of hospital
      admissions in past year (OR 4.3, P = .02), use of home nebulizer (OR 3.6, P =
      .05) and the lack of a written asthma action plan (OR 3.3, P = .03) were
      independently associated with frequent visits to the ED. We conclude that a
      substantial proportion of the patients that visit the ED are FV. These patients
      are more likely to have hospital admission in the past year, to use a home
      nebulizer, and to lack a written asthma action plan. They should be considered
      the most important target for asthma education.

PMID- 14580001
TI  - Asthma severity, psychiatric morbidity, and quality of life: correlation with
      inhaled corticosteroid dose.
AB  - OBJECTIVES: Psychiatric phenomena in asthma has been debated for some time.
      Inhaled corticosteroids (ICS) are a significant part of treatment. We attempted
      to quantify the prevalence of psychiatric morbidity relative to asthma severity,
      quality of life (QOL), and ICS dose. DATA SOURCES: Fifty asthmatic patients (18 >
      or = X < or =75 years) on ICS, attending an urban clinic had asthma and ICS dose
      stratified by symptom severity and preparation potency. Peak flow and forced
      expiratory volume in 1 second (FEV1) were measured. Patients completed general
      QOL and disease-specific QOL questionnaires, along with psychiatric rating
      scales. RESULTS: Patients (n = 50) clustered in the 40-59 year range (n = 27,
      54%) and were predominantly female (n = 44, 88%) Hispanics (n = 30, 60%), with
      mild-moderate asthma (n = 18, 36%) and on low-dose ICS (n = 22, 44%). FEV1 ranged
      from 32 to 123 (mean 76.98, SE 3.01). Peak flow ranged from 210 to 590 (mean
      407.83, SE 13.24). Prevalence of anxiety and depressive symptoms were higher than
      expected (Kendall's tau-c, n = 50, P < .01). Independently, high ICS dose and
      asthma severity correlated directly with all measures of psychiatric morbidity
      (Pearson's r0.781, P < .01). High ICS dose correlated inversely with SF-36 Mental
      Component Scale (Pearson's r0.681, P < .01) and directly with FEV1 and peak flow
      when age/sex adjusted (Spearman's rho: 0.660, P < .001). CONCLUSIONS: Psychiatric
      morbidity is more prevalent in this population and impacts negatively on QOL. Use
      of high-dose ICS benefited pulmonary function and "physical" QOL, yet may have
      negatively affected patients' mental well-being. Longitudinal follow-up,
      extension of sample size, and better study control would allow closer
      approximation of possible negative associations with ICS.

PMID- 14580002
TI  - A survey on awareness and utilization of new asthma management guidelines in
      Japan.
AB  - The present questionnaire survey, designed to interview Japanese internists and
      pediatricians who were specialists or nonspecialists in allergy or asthma, was
      conducted to determine the acceptance of "Asthma Prevention and Management
      Guidelines 1998" 1 year after release. The surveyor visited each physician and
      used the questionnaire form at the interview. Replies were obtained from a total
      of 5,963 physicians. The percentage of physicians who were aware of the
      guidelines was 96% among specialists and 68% among nonspecialists. Among the
      internists who were aware of the guidelines, the percentage of physicians giving
      a reply of "I refer to them often" or "I refer to them" in the actual diagnosis
      and management of asthma was 95% among specialists and 92% among nonspecialists.
      Therefore, reference was very high. Except for nonspecialists among
      pediatricians, not less than 60% of physicians expected that propagation of the
      present guidelines would allow a further decrease in asthma death and further
      improvement of patient's quality of life. The present survey revealed an increase
      in guideline awareness over the last several years, which was especially marked
      in nonspecialists. Furthermore, high reference and high expectancy also verified
      that physicians recognize the contents of the present guidelines as appropriate.

PMID- 14580003
TI  - Quality of published clinical trials on asthma.
AB  - The quality of 287 clinical trials on asthma treatment published between 1984 and
      1997 is described in this article, using a scale adding to a maximum of 14
      points. The mean quality score was 8.60 (standard deviation 1.55). Quality
      improved throughout time from 8.17 +/- 1.40 before 1989 until 9.55 +/- 1.66 after
      1992. Several methodological issues were associated with higher quality, namely
      parallel design, longer length of the follow-up, complete description of the
      exclusion criteria, description of the initial and ending recruitment dates,
      higher sample size, explicit sample size calculation, blinding, full description
      of randomization, intention-to-treat analysis, full description of the
      intervention, and evaluation of bias. The higher statistical significance,
      however, was not associated with higher clinical trial quality.

PMID- 14580005
TI  - Toxicological diversity: making room for the U-shaped dose-response.

PMID- 14580004
TI  - Fenoterol delivery by Respimat soft mist inhaler versus CFC metered dose inhaler:
      cumulative dose-response study in asthma patients.
AB  - OBJECTIVES: Respimat (RMT) soft mist inhaler (SMI) is a novel, propellant-free
      alternative to chlorofluorocarbon metered-dose inhalers (CFC-MDIs). The aim of
      this study was to evaluate the safety and establish the equipotent dose of
      fenoterol delivered by RMT SMI vs. a conventional MDI. DESIGN: Double-blind,
      randomized, crossover, comparative study between fenoterol inhaled via RMT
      (either 50 microg/actuation, RMT50; or 100 microg/actuation. RMT100) and MDI (100
      microg/actuation; MDI100). PATIENTS AND INTERVENTIONS: A total of 41 asthma
      patients received cumulative doses of fenoterol 600 microg (RMT50) or 1200 microg
      (RMT100 and MDI100) on 3 test days. MEASUREMENTS AND RESULTS: The bronchodilator
      response (forced expiratory volume in 1 second [FEV1]) was considered
      therapeutically equivalent (i.e., noninferior) if the 95% confidence intervals
      for the difference in their mean changes from baseline were within limits of +/-
      0.15L. Systemic exposure was evaluated from plasma fenoterol levels. Adverse
      events (AEs) were recorded. RMT50 and RMT100 produced noninferior
      bronchodilatation to MDI100 from 30minutes after the first dose. RMT50 showed
      equivalent safety and tolerability to MDI100, whereas RMT100 produced a higher
      incidence of AEs, a significantly greater plasma potassium reduction and a
      significant increase in pulse rate. Fenoterol plasma levels were twice as high
      with RMT100 as with RMT50 or MDI100. CONCLUSIONS; The nominal dose of fenoterol
      administered via RMT SMI can be at least halved to achieve equivalent efficacy,
      safety, and tolerability to a MDI.

PMID- 14580006
TI  - Plant poisonings in children in the Czech Republic, 1996-2001.
AB  - Ingestion of or exposure to potentially poisonous plants is a relatively common
      presenting complaint in hospital paediatric departments, especially amongst
      toddlers. We present a retrospective study conducted to review the hospital
      admissions following acute childhood poisoning with plants in the Czech Republic
      over a 6-year period from 1996 to 2001. Six university hospital paediatric
      departments and two local hospital paediatric departments were involved in the
      study. Information and complete data on the cases were collected on the basis of
      all hospital medical records and internal hospital database outcomes. A total of
      174 plant exposures were analysed to tabulate the list of top species involved in
      plant poisonings. The aims were to provide classification according to agent
      frequency, clinical presentations, severity of symptoms expressed, affected age
      groups and gender of patients and to evaluate the treatment according to patient
      outcome. The most frequent ingestions were of thorn apple seeds (14.9%), followed
      by dumb cane exposures (11.5%) and common yew (9.8%). Thorn apple, dumb cane,
      golden chain and raw beans caused the most serious symptoms. There were no
      fatalities reported out of the reviewed medical records. Complete data on plant
      poisoning in children from all over the territory of the Czech Republic are not
      available; however, we believe that the frequency of causes and the rank of plant
      species commonly involved are properly reflected in our study.

PMID- 14580007
TI  - Aqueous extract of walnut (Juglans regia L.) protects mice against
      cyclophosphamide-induced biochemical toxicity.
AB  - Walnut (Juglans regia L.) is extensively used in traditional systems of medicine
      for treatment of various ailments. It is described as an anticancer, tonic, blood
      purifier and detoxifier agent. The present study was undertaken to investigate
      modulatory effects of walnut extract on the toxicity of an anticancer drug,
      cyclophosphamide (CP) with special reference to protection against disruption of
      drug metabolizing and antioxidant enzymes. Plant extract+CP group animals showed
      restoration in the level of cytochrome P450 (CYP) content and in the activities
      of glutathione S-transferase (GST), glutathione peroxidase (GP) and catalase
      (CAT) in both liver and kidneys. But plant extract restored the activity of
      superoxide dismutase (SOD) and the level of reduced glutathione (GSH) in the
      kidneys only when compared with CP-treated animals. Plant extract treatment alone
      caused significant reduction in the content of CYP in the kidneys mainly. The
      extract showed a significant increase in the level of GSH and in the activities
      of GP in both the tissues and CAT in liver only, whereas no significant change
      was observed in the activities of GST and SOD. CP treatment resulted in a
      significant (P < 0.01) increase in the lipid peroxidation (LPO) in the liver and
      kidneys compared with controls, while the extract+CP treated group showed a
      significant decrease in the LPO in liver and kidneys when compared with the CP
      treated group. The study shows that the use of J. regia extract might be helpful
      in abrogation of CP toxicity during the chemotherapy.

PMID- 14580008
TI  - The effect of chronic lead exposure on the course of schistosomiasis in hamsters
      and the protective effect of the antioxidant preparation 'Antox'.
AB  - Eighty adult male hamsters were used in this study, 20 of them were divided
      equally into a noninfected, nontreated control group and chronic lead exposed
      groups, which were given lead acetate intraperitoneally, dissolved in distilled
      water, 2 mg/kg/day for seven weeks. Then, two experiments were carried out on the
      remaining animals. Each experiment included 30 animals and was divided equally
      into three groups. Experiment A was carried out on the following groups:
      Schistosoma mansoni infected group, S. mansoni infected and chronic lead exposed
      group and S. mansoni infected, chronic lead exposed and 'Antox' treated group.
      Experiment B was done following the same design except that infection was carried
      out using Schistosoma haematobium cercaria. Chronic lead exposure of Schistosoma
      infected groups showed significant reductions in worm burden, tissue egg load and
      ova excretion in stool, liver and intestine. Compared with the control group,
      there were insignificant increases in serum and hepatic glutathione and
      malondialdehyde levels and a significant increase in hepatic 8-oxodeoxyguanosine
      phosphate (8-Ox-Dg) levels in Schistosoma infected groups. However, there was a
      significant increase in hepatic and blood lead levels, oxidative stress
      parameters and in the hepatic 8-Ox-Dg level in Schistosoma infected and chronic
      lead exposed groups as compared with their corresponding Schistosoma only
      infected groups. This study revealed a significant reduction in oxidative stress
      parameters as well as in blood and hepatic lead levels and in hepatic 8-Ox-Dg
      levels after giving Antox to the Schistosoma infected and chronic lead exposed
      groups. However, Antox increased insignificantly all the parasitological
      parameters studied in the Schistosoma infected and chronic lead exposed groups.

PMID- 14580009
TI  - Hematological, hemostatic and clinical chemistry disturbances induced by Crotalus
      durissus terrificus snake venom in dogs.
AB  - The aim of this study was to investigate the hematological, hemostatic and
      biochemical disturbances induced by the injection of Crotalus durissus terrificus
      venom in dogs under controlled conditions. For this purpose three groups of
      animals were used: an experimental group (E), which was injected i.m. with C.
      durissus terrificus venom (1 mg/kg); and two control groups--antivenom (AV) and
      control (C)--which were injected i.m. with 150 mM NaCl. Groups E and AV were
      treated i.v. with Crotalus antivenom 2 hours after the first injection. Serum
      levels of alkaline phosphatase and alanine aminotransferase were increased in
      groups E and AV at 24 and 48 hours after serumtherapy, respectively. The
      increased serum levels of myoglobin, creatine kinase and aspartate
      aminotransferase demonstrated that animals developed rhabdomyolysis. A persistent
      neutrophilic leukocytosis was already noticeable at 2 hours after envenomation
      and lasted even after serumtherapy. The animals of groups E and AV presented
      eosinopenia 24 hours after serumtherapy, and collagen-induced platelet
      hypoaggregation was observed without thrombocytopenia. Increased levels of
      fibrinogen/fibrin degradation products (FnDP/FgDP), hypofibrinogenemia, and
      alpha2-antiplasmin consumption were observed at 2 hours after envenomation,
      indicating secondary activation of fibrinolysis. Our data suggest that the
      biochemical and hemostatic disturbances induced by C. durissus terrificus venom
      in dogs are related to its myotoxic and thrombin-like activities.

PMID- 14580010
TI  - Comparison of human exposures to selected chemicals with thresholds from NTP
      carcinogenicity studies in rodents.
AB  - The National Toxicology Program (NTP) Technical Reports online database was
      reviewed to find chemicals that were reported to show clear evidence of
      carcinogenicity in the NTP rodent studies and for which data on human exposure
      could be found. Six representative compounds were selected. Three volatile
      compounds: ethyl benzene, perchloroethylene, and methylene chloride; two drugs in
      current use: phenytoin and primidone; and one naturally occurring, widely used,
      flavor: allyl isothiocyanate, were selected. The carcinogenicity data from each
      of the NTP Technical Reports were plotted using the Rozman scale to determine the
      threshold for carcinogenicity from the rodent studies. The human exposures for
      each chemical were calculated and compared with that threshold. The thresholds
      for carcinogenicity of the three volatile compounds were several orders of
      magnitude above the levels present in ambient air in the USA. The Threshold Limit
      Value (TLV) of the American Conference of Governmental Industrial Hygienists
      (ACGIH) for these three compounds varied between several orders of magnitude
      below the carcinogenicity threshold to being at the threshold. The maximum
      recommended doses of both drugs were at the carcinogenicity threshold. The
      estimated mean daily human consumption of the natural flavor was less than 100 x
      below the carcinogenicity threshold. This method of comparison between human
      exposure and animal carcinogenicity studies is more objective and informative
      than those in current use.

PMID- 14580011
TI  - A comparison of the decontamination efficacy of foam-making blends based on
      cationic and nonionic tensides against organophosphorus compounds determined in
      vitro and in vivo.
AB  - The ability of foam-making blends to decontaminate the skin exposed to
      organophosphorus compounds was tested. The appropriate composition and
      rheological features (stability, grade of foaming) of tested blends were
      evaluated by in vitro methods and their ability to remove the contaminants from
      hard surface and to transform the contaminants into nontoxic compounds was
      evaluated by in vivo methods. The blends containing cationic and nonionic
      tensides as well as alkalized hydrogen peroxide seem to be the most efficacious
      to decontaminate the skin exposed to organophosphorus compounds according to the
      literature data. The composition of tested blends was optimized because
      particular components often have antagonistic effects. Cationic tensides support
      the reactivity of the blend and control the grade of foaming. Nonionic tensides
      control the stability of the foams but also react as retardants of the reactivity
      of the foams. Hydrogen peroxide is a real reacting component when it is
      transformed into hydrogen peroxide anion. It also acts as buffer if pH is higher
      than 11. Our in vivo results confirm that Desam OX (34 and 68%) and the foam
      making blend containing benzalkonium chloride--Althosan MB (8%), Slovasol 2510
      (2%) and hydrogen peroxide (3%) alkalized at pH 12 seem to be the most
      efficacious to remove contaminants (soman, VX) from the skin and transform them
      into nontoxic compounds. Therefore they could be used for primary decontamination
      of chemical casualties contaminated with nerve agents in the field condition.

PMID- 14580012
TI  - HPLC/MS findings in a fatality involving sustained-release verapamil.
AB  - A fatality involving verapamil, a calcium channel blocker agent, is presented. A
      51-year old male ingested 7200 mg of sustained-release (SR) verapamil at T0 and
      died 40 hours later of refractory, mixed shock and multiorgan failure. The
      symptoms displayed during hospitalization were quite typical and involved altered
      consciousness, hypotension, bradycardia, atrioventricular block, metabolic
      acidosis and renal failure. Verapamil and its primary metabolite, norverapamil,
      were assayed on eight plasma and two urine samples, successively taken between
      the admission to the ICU (T0 + 4 hours) and time of death, using an original high
      performance liquid chromatography/mass spectrometry (HPLC/MS) procedure with
      verapamil-d3 as internal standard. Plasma verapamil and norverapamil levels on
      admission were 0.94 and 1.36 microg/mL, respectively, then verapamil remained
      practically unchanged throughout the hospitalization (0.85 microg/mL at T0 + 40
      hours). The discussion focuses on the detrimental role of SR formulations in
      overdose, with special emphasis on the risk of pharma-cobezoar development
      already reported with SR-verapamil. To our knowledge, this is the first report of
      a verapamil fatality documented by repeated plasma measurements of the drug
      during the antemortem period.

PMID- 14580013
TI  - Models, definitions, and criteria of frailty.

PMID- 14580014
TI  - Orthodontic education--who pays the bills?

PMID- 14580015
TI  - Amount and direction of temporomandibular joint growth changes in Herbst
      treatment: a cephalometric long-term investigation.
AB  - The amount and direction of condylar growth, glenoid fossa displacement, and
      "effective" temporomandibular joint (TMJ) changes (a summation of condylar
      growth, glenoid fossa displacement, and condylar position changes within the
      fossa) were analyzed in 35 Class II, Division 1 malocclusions (23 boys and 12
      girls) treated with the Herbst appliance. Lateral head films in habitual
      occlusion and with the mouth wide open from before (T1) and after 7.5 months of
      Herbst treatment (T2) as well as 7.5 months (T3) and three years (T4) after
      treatment were evaluated. As a control group, a sample of 12 untreated male Class
      II Division I malocclusions was used during a 7.5-month time period corresponding
      to the treatment period (T2-T1) of the Herbst cases. The results revealed that
      during the treatment period (T2-T1) condylar growth was directed posteriorly
      about twice the amount as in the control subjects, and the fossa was displaced in
      an anterior inferior direction. The effective TMJ changes showed a pattern
      similar to condylar growth but were more pronounced. During the first
      posttreatment period (T3-T2), all TMJ changes reverted. The glenoid fossa was
      displaced backward; the amount of condylar growth and effective TMJ changes was
      reduced, and the changes were more superiorly directed. During the second
      posttreatment period (T4-T3), all TMJ changes were considered physiological.
      CONCLUSION: During Herbst treatment, the amount and direction of TMJ changes
      (condylar growth, fossa displacement, and effective TMJ changes) were only
      temporarily affected favorably by Herbst treatment.

PMID- 14580016
TI  - Incisor crowding in untreated persons 15-50 years of age: United States, 1988
      1994.
AB  - The purpose of this study was to (1) describe the prevalence of mandibular
      incisor irregularity (II) among untreated adults in the United States and (2)
      evaluate the factors explaining individual differences in II. Data were derived
      for a random sample of 9044 individuals (49% male and 51% female; 35% Mexican
      American, 34% black, and 31% white) between 15 and 50 years of age collected as
      part of the Third National Health and Nutrition Examination Survey. Although the
      differences were small (0.5 mm), males had significantly greater II than did
      females; blacks showed less II than did whites (0.9 mm) and Mexican Americans
      (1.1 mm). Family income was negatively related with II. Incisor irregularity
      increased in a curvilinear fashion with age, with the greatest increases
      occurring during early adulthood. Although the number of premolars and molars
      (first and second) were positively related with II, the presence of third molars
      had a negative effect on II. Multivariate Poisson regression analyses showed that
      the ethnicity, the number of first and second molars, sex, and age combined to
      explain differences in II. Odds ratios were relatively low, indicating that these
      factors explained relatively small amounts of between-subject variation. We
      conclude that (1) approximately 50% of individuals in the United States who were
      15-50 years of age have little or no II, 23% have moderate II, and 17% have
      severe irregularity, (2) erupted third molars are not associated with increased
      crowding, (3) crowding increases most during early adulthood, and (4) although
      individual differences in crowding are multifactorial, the primary determinants
      remain unidentified.

PMID- 14580017
TI  - Longitudinal dental arch changes in the mixed dentition.
AB  - The purpose of this study was to investigate dental arch changes that occurred
      during the mixed dentition in 30 normal occlusion children. Two analyses were
      done. The first one was at the age of early mixed dentition and the second at the
      age of late mixed dentition. Most width variables were greater in the males, and
      depth variables greater in the female subjects. A directionally larger left side
      of the maxilla and right side of the mandible were observed. Our findings
      indicate that most arch width dimensions are established in the early mixed
      dentition. We conclude that the period between the early and late mixed dentition
      is suitable for environmental factors to disrupt the ideal symmetrical
      developmental pattern because more growth and developmental changes occur after a
      relatively stabile period of deciduous dentition.

PMID- 14580018
TI  - Skeletal and dental contributions to posterior crossbites.
AB  - The objective of this retrospective study was to compare skeletal and dental arch
      morphology of children with posterior crossbites with a control group of children
      without posterior crossbites. The study included 93 patients with a posterior
      crossbite (33 boys and 60 girls) and 97 patients without a posterior crossbite
      (50 boys and 47 girls). Skeletal and dental characteristics between the two
      groups were compared using measurements of dental casts, and lateral and
      posteroanterior cephalograms. Univariate analyses revealed that seven
      characteristics were significantly different between the crossbite and non
      crossbite groups: mandibular plane angle, lower face height, skeletal maxillary
      to mandibular width ratio, maxillary intermolar width, mandibular intermolar
      width, maxillary to mandibular intermolar width ratio, and mandibular unit
      length. Using maxillary to madibular intermolar width ratio as the outcome
      measure, a stepwise variable selection technique, analyzed all 190 patients and
      found only two variables significantly associated with this measure: skeletal
      maxillary to mandibular width ratio and lower face height. The coefficient of
      multiple determination for this model was only 13%, indicating that these two
      variables accounted for only a small portion in the variation of the ratio
      between the maxillary and mandibular intermolar widths.

PMID- 14580019
TI  - Muscular adaptation to gradual advancement of the mandible.
AB  - Muscular activity of the superficial masseter muscle and anterior portion of the
      temporal muscle before, during, and after treatment, with gradual advancement of
      the mandible, was evaluated by assessing the average integrated electromyogram
      (EMG) with the mandible in retruded position (RP) and incisal edge-to-edge (EE)
      position on 23 consecutive subjects with skeletal Class II malocclusion. Toward
      the end of active treatment and follow-up, the RP position and EE position
      coincided. At any given registration, the EMG activity of the masseter muscle was
      at least twice (P < .001) that of the anterior portion of the temporal muscle.
      The EMG activity in RP for the anterior portion of the temporal muscle was not
      affected significantly, whereas the EMG activity at EE position decreased
      significantly (P < .05) during the initial treatment, but, thereafter, it
      increased continuously. The difference in EMG activity between six months of
      follow-up and pretreatment level reached statistical significance (P < .05). For
      the masseter muscle, the EMG activity at both RP and EE position was reduced
      about 20% during the initial treatment but returned to the pretreatment level
      during active treatment and exceeded pretreatment level by approximately 30% to
      50% at two and six months of follow-up, respectively. In conclusion, it seemed
      that gradual advancement affected the anterior portion of the temporal muscle to
      a minor extent, whereas the effect on the masseter muscle was significant.

PMID- 14580020
TI  - Effect of rapid maxillary expansion on nocturnal enuresis.
AB  - One of the effects of rapid maxillary expansion (RME) is a reduction in nighttime
      bed-wetting. The aim of this prospective study was to investigate the effects of
      RME on nocturnal enuresis (NE) in children who are liable to psychosocial stress
      conditions. Eight children (six boys and two girls) who had not responded to
      different conventional medical treatments were included in the study. The
      subjects were between eight and 11 years of age with a mean age of nine years
      five months, and were residents of a government orphanage. All the children wet
      the bed at least one time every night and previously had been subjected to
      unsuccessful conventional treatment modalities. Maxillary expansion was performed
      using a rigid acrylic RME device. Lateral and PA cephalometric films and dental
      casts were used in the assessment of the dentofacial and nasopharyngeal
      structures. Data were analyzed using a paired t-test. In seven of the eight
      children, remarkable improvement was observed in NE after three to six mm RME. At
      the end of eight months observation, the mean rate of improvement in bed-wetting
      in the seven successful subjects was 74.2% (57.6-87.5%). The findings also
      indicated significant changes in the nasomaxillary structures and nasopharyngeal
      airway dimensions with the use of RME. However, none of the subjects became
      completely dry, and the disorder is probably multicausal including psychological
      emotions and tensions. This study demonstrated that RME treatment could cause
      relief for the enuretic children. However, the long-term success rate is still
      questionable.

PMID- 14580021
TI  - Three-dimensional analysis of dental casts based on a newly defined palatal
      reference plane.
AB  - The purpose of this study was to establish a new method for orthodontic diagnosis
      that integrates the three-dimensional (3-D) shape of a dental cast and the
      craniofacial morphology using a newly defined palatal reference plane. We also
      measured the accuracy of this new palatal reference plane as a reference for
      measurement and its spatial relationship to the framework of the craniofacial
      skeleton using lateral and frontal cephalometric radiography and maxillary dental
      casts, which were transferred using an anatomical face-bow. Eighteen female
      subjects were included in this study. The new reference plane in dental cast
      analysis corresponded to the A-PNS plane in the lateral view and to the J-J'
      plane in the frontal view, which have been shown to be sufficiently accurate as a
      reference for measurement. These results indicate that the application of this
      palatal reference plane, as a reference structure, should provide accurate and
      abundant 3-D data concerning malocclusion.

PMID- 14580022
TI  - 99mTechnetium-labeled methylene diphosphonate uptake in maxillary bone during and
      after rapid maxillary expansion.
AB  - The purpose of this study was to evaluate bone activity at the midpalatal suture
      that had been biomechanically stimulated by rapid maxillary expansion (RME). A
      rigid acrylic-bonded expansion device with a maxiskeleton screw was used for RME
      in three patients who were in three different growth periods. The screw was
      activated twice a day by 1/4 turns. After sufficient expansion, the screw was
      fixed with acrylic resin, and the same appliance was used as a removable
      retention plate for three months. Single photone emission computed tomography
      (SPECT) bone scintigraphy records were obtained before (T1) and at the end of RME
      (T2) and three months after the retention period (T3). According to the
      scintigraphic records, the increase in bone activity was highest in the anterior
      and medial sections on both the left and right sides of the maxilla in all cases.
      After three months of retention, the bone activity returned to its original
      level. Therefore, it may be stated that the retention period of three months was
      sufficient for bone reorganization.

PMID- 14580023
TI  - Magnetic resonance imaging assessment of positional relationship between the disk
      and condyle in asymptomatic young adult mandibular prognathism.
AB  - The aim of this study was to clarify disk position relative to the condyle and
      condylar position relative to the glenoid fossa in clinically asymptomatic and
      orthodontically untreated young adult Class III patients by magnetic resonance
      imaging (MRI). In addition, the relationship between skeletal Class III
      morphology and positional changes of the temporomandibular joint (TMJ) components
      were investigated. The material consisted of 34 bilateral sagittal oblique TMJ MR
      images (MRIs) and lateral cephalometric radiographs taken in a closed mouth
      position. The mean age of the patients was 20.71 +/- 0.82 years (range 16-29
      years). Only clinically symptom-free subjects were included in this study.
      Measurements made on the MRIs and lateral cephalographs were used to calculate
      means and minimum and maximum values. The right and left TMJ variables were
      compared with the Student's t-test. Correlation coefficients between bilateral
      TMJ variables and skeletal variables were calculated. In the right TMJ, the disk
      was positioned anteriorly and the condyle was positioned posteriorly, whereas the
      left TMJ was normal. A negative correlation existed between the vertical skeletal
      morphology and the anterior joint space of the TMJ. A positive correlation was
      found between the left disk position and the vertical skeletal morphology because
      of the differentiation of the condylar head angle in each side. As a result,
      clinically asymptomatic Class III patients may be candidates for TMJ
      derangements. For this reason, clinical and visual examinations should be
      performed simultaneously to eliminate diagnostic errors before orthognathic
      treatment.

PMID- 14580024
TI  - Clinical use of the ABO-Scoring Index: reliability and subtraction frequency.
AB  - This study tested the reliability and subtraction frequency of the study model
      scoring system of the American Board of Orthodontists (ABO). We used a sample of
      36 posttreatment study models that were selected randomly from six different
      orthodontic offices. Intrajudge and interjudge reliability was calculated using
      nonparametric statistics (Spearman rank coefficient, Wilcoxon, Kruskal-Wallis,
      and Mann-Whitney tests). We found differences ranging from 3 to 6 subtraction
      points (total score) for intrajudge scoring between two sessions. For overall
      total ABO score, the average correlation was .77. Intrajudge correlation was
      greatest for occlusal relationships and least for interproximal contacts.
      Interjudge correlation for ABO score averaged r = .85. Correlation was greatest
      for buccolingual inclination and least for overjet. The data show that some
      judges, on average, were much more lenient than others and that this resulted in
      a range of total scores between 19.7 and 27.5. Most of the deductions were found
      in the buccal segments and most were related to the second molars. We present
      these findings in the context of clinicians preparing for the ABO phase III
      examination and for orthodontists in their ongoing evaluation of clinical
      results.

PMID- 14580025
TI  - Bond strengths of orthodontic bracket after acid-etched, Er:YAG laser-irradiated
      and combined treatment on enamel surface.
AB  - Laser ablation has been proposed as an alternative method to acid etching:
      however, previous studies have obtained contrasting results. The purpose of this
      study was to compare the bond strengths after acid etching, laser ablation, acid
      etching followed by laser ablation, and laser ablation followed by acid etching.
      Forty specimens were randomly assigned to one of the four groups. Two more
      specimens in each group did not undergo bond test and were prepared for
      observation with scanning electron microscope (SEM) after the four kinds of
      surface treatment. After the bond test, all specimens were inspected under the
      digital stereomicroscope and SEM to record the bond failure mode. Student's t
      test results showed that the mean bond strength (13.0 +/- 2.4 N) of the laser
      group was not significantly different from that of the acid-etched group (11.8 +/
      1.8 N) (P > .05). However, this strength was significantly higher than that of
      the acid-etched then laser-ablated group (10.4 +/- 1.4 N) or that of the laser
      ablated then acid-etched group (9.1 +/- 1.8 N). The failure modes occurred
      predominantly at the bracket-resin interface. Er:YAG laser ablation consumed less
      time compared with the acid-etching technique. Therefore, Er:YAG laser ablation
      can be an alternative tool to conventional acid etching.

PMID- 14580026
TI  - Possibility of blood and hepatitis B contamination through aerosols generated
      during debonding procedures.
AB  - The primary purpose of this study was to investigate the presence of blood or
      blood elements in aerosols generated during the debonding procedures. The
      presence of three hepatitis B carriers in the study group led us to investigate
      the possibility of hepatitis B virus (HBV) contamination through aerosols, which
      was the secondary purpose of the study. The study group consisted of 26 patients
      who had a mean age of 16 +/- 2 years. Collection of aerosol samples was done
      using a saliva ejector that fit on the handle of the high-speed dental instrument
      and was attached to a mobile evacuator. A second evacuator was used to remove and
      collect excess fluid accumulated in the patient's mouth. The guaiac method was
      used to investigate the presence of occult blood in aerosol and in excess fluid
      samples. Serum, excess fluid, and aerosol samples of three hepatitis B carriers
      were tested by enzyme-linked immunosorbent assay for detecting hepatitis B
      surface antigen (HBsAg) and by polymerase chain reaction for detecting HBV
      deoxyribonucleic acid (DNA). Blood was found in all the aerosols and in excess
      fluid samples. HBsAg was detected in excess fluid samples of the two hepatitis B
      carriers, whereas HBV-DNA was detected in only one of the excess fluid samples.
      HBsAg and HBV-DNA were detected in aerosol sample of only one hepatitis B
      carrier. The results of this study showed that aerosols generated during the
      debonding procedure should always be considered as potential hazards to health.

PMID- 14580027
TI  - Effects of a mechanical interdental cleaning device on oral hygiene in patients
      with lingual brackets.
AB  - This study was aimed at determining the influence of a battery-operated
      interdental cleaning device (icd) (WaterPik Flosser) on the oral hygiene of 32
      female right-handed patients (mean age 25.9 years) with lingual brackets in the
      upper (n = 29) and or in the lower arch (n = 25). Approximal plaque index (API)
      and bleeding on probing (BOP) were recorded at the lingual surfaces by a single
      blinded examiner before application (t0), on average 38.6 days after (t1), and
      again on average 46.0 days after (t2) the application of the icd. The patients
      used the icd once a day in the second and fourth quadrants only (icdq). In all
      quadrants (icdq and non-icd quadrants [n-icdq]), oral hygiene was performed with
      a manual toothbrush. Of the patients enrolled in the study, 96.9% found the icd
      subjectively very helpful to moderately helpful for cleaning their teeth and
      65.6% had the subjective impression that their teeth were cleaner with the
      appliance. Despite those positive subjective assessments, an objective comparison
      of the icdqs with the n-icdqs revealed no statistically significant differences
      in the mean changes in API and BOP from t0 to t1, from t0 to t2, or from t1 to
      t2. Because there were spectacular improvements in API in all quadrants, the
      improvements could be interpreted as an outcome of the instruction and motivation
      given to the patients, the increasing awareness of oral hygiene, and the greater
      skill in using the toothbrush in the course of time.

PMID- 14580029
TI  - Intrusion of supererupted molars with titanium miniplate anchorage.
AB  - Titanium miniplates, normally used in orthognathic surgery for osteotomy
      fixation, were placed in the maxilla and mandible for skeletal anchorage to
      orthodontically intrude severely hypererupted unopposed molars.

PMID- 14580028
TI  - A systematic review concerning early orthodontic treatment of unilateral
      posterior crossbite.
AB  - The aim of this study was to assess the orthodontic treatment effects on
      unilateral posterior crossbite in the primary and early mixed dentition by
      systematically reviewing the literature. A literature search was performed by
      applying the Medline database (Entrez PubMed) and covering the period from
      January 1966 to October 2002. The inclusion criteria were primary and early mixed
      dentition with unilateral posterior crossbite, randomized controlled trials
      (RCT), prospective and retrospective studies with concurrent untreated as well as
      normal controls, and clinical trials comparing at least two treatment strategies
      without any untreated or normal group involved. Two reviewers extracted the data
      independently and also assessed the quality of the studies. The search strategy
      resulted in 1001 articles, and 12 met the inclusion criteria. Two RCTs of early
      treatment of crossbite have been performed, and these two studies support
      grinding as treatment in the primary dentition. There is no scientific evidence
      available to show which of the treatment modalities, grinding, Quad-helix,
      expansion plates, or rapid maxillary expansion, is the most effective. Most of
      the studies have serious problems of lack of power because of small sample size,
      bias and confounding variables, lack of method error analysis, blinding in
      measurements, and deficient or lack of statistical methods. To obtain reliable
      scientific evidence, better-controlled RCTs with sufficient sample sizes are
      needed to determine which treatment is the most effective for early correction of
      unilateral posterior crossbite. Future studies should also include assessments of
      long-term stability as well as analysis of costs and side effects of the
      interventions.

PMID- 14580030
TI  - Use of distraction osteogenesis in cleft palate patients.
AB  - Distraction osteogenesis (DO) has been used recently to correct maxillary
      hypoplasia with predictable and stable results. In patients with clefts of the
      secondary palate, DO can also be used to aid in vertical alveolus augmentation
      and rapid orthodontic tooth movement. If an osteotomized dental arch can be
      transported to a new position without complications, it would reduce or eliminate
      the need for a secondary bone graft to the cleft alveolus in cleft patients and
      help prevent dentoalveolar defects by approximating the native alveolar bone and
      gingiva. Mobilizing a segment in the dentoalveolar region also results in the
      creation of new bone and attached gingiva. This report shows that the application
      of DO for skeletal expansion and rapid movement of tooth-bone segments should
      receive more careful consideration in the treatment of patients with clefts of
      the palate.

PMID- 14580031
TI  - An adolescent case of anterior open bite with masticatory muscle dysfunction.
AB  - In adolescence an open bite is likely to be induced by various causes, and most
      patients with open bite show masticatory muscle dysfunction. The orthodontic
      correction of an open bite may lead to the recovery of harmonious stomatognathic
      function. This article reports treatment for a 12-year and 10-month-old female
      patient with an anterior open bite. She complained of occlusal disturbances due
      to an anterior open bite. Before the eruption of the upper second molars, she
      recognized the presence of occlusal contacts between the upper and lower anterior
      teeth. Before treatment, the activity of the masticatory muscles was relatively
      low during clenching. An upper lingual arch with an accessory spring to eliminate
      the premature contact and to improve the anterior open bite plus conventional
      fixed appliances for tooth alignment was selected as the treatment plan.
      Immediately after improvement of the open bite, the muscle activity became
      slightly greater than that at the initial stage. The total treatment time was 13
      months. After treatment, an acceptable occlusion was achieved, the masticatory
      muscles were working harmoniously, and their activity was much higher than that
      at the initial stage. After a 2-year retention period, an acceptable occlusion
      was maintained without recurrence of the open bite, indicating a long-term
      stability of occlusion. The result of this treatment indicated that correction of
      open bite is of great importance for prevention of skeletal impairment and
      recovery of harmonious stomatognathic function lost by an unstable occlusion.

PMID- 14580033
TI  - The use of botulinum toxin in pediatric disorders.
AB  - Botulinum toxins have an exciting and important role in treating the child with
      hypertonia. The guidelines presented in this article are those that have been
      published representing the safe use of botulinum toxins in children. Experience
      and a decade of research have provided the framework for using botulinum toxins
      in decreasing deformity and promoting function. In children, a window of
      opportunity exists with botulinum toxin that allows improved motor control and
      elongation of shortened muscles. Although 3 to 4 months in an adult life is
      short, for a child it is a relatively greater proportion of their life experience
      and may be long enough for skill development. The improvement noted in function
      after botulinum toxin use is facilitated by comprehensive rehabilitation. The
      pediatric physiatrist has a unique role in the management of children with
      cerebral palsy and other conditions with hypertonia. Their knowledge and training
      reflect an understanding of anatomy and development that allows accurate
      evaluation of specific functional problems in children related to hypertonia. The
      pediatric physiatrist has experience in localization of muscles by EMG, nerve
      stimulation, and surface anatomy. Although many other physicians inject botulinum
      toxins, goal-directed management is the cornerstone to the physiatrist's thinking
      and treatment plan. Orthopedic surgery ultimately may be the intervention of
      choice if persistent contracture or progression of contractures occurs. Working
      in collaboration with an orthopedist identifies the timing of optimal surgical
      intervention for alignment. For persistent and severe hypertonia, the treatment
      team includes a neurosurgeon. All options for spasticity, such as selective
      posterior rhizotomy and intrathecal baclofen, should be considered. Re-evaluation
      of the child after selective dorsal rhizotomy or intrathecal baclofen is
      appropriate and should be discussed with therapists for focal intervention.
      Communication between members of the team and the family is desirable and
      frequently is one of the major contributions of the pediatric physiatrist. For
      children with focal hypertonia, botulinum toxins offer a dramatic but temporary
      repeatable change that affects rehabilitation. Research rapidly has captured the
      positive effect of the toxins on impairment and functional limitations. Not to be
      overlooked are outcomes related to quality of life. The long-term use of
      botulinum toxins and the role the toxins play throughout the life span of the
      person with a childhood hypertonic disorder are yet to be determined.

PMID- 14580032
TI  - Personal computer-based three-dimensional computed tomographic images of the
      teeth for evaluating supernumerary or ectopically impacted teeth.
AB  - This study describes the use of personal computer (PC)-based three-dimensional
      computed tomographic (3D CT) images in the evaluation of supernumerary and
      ectopically impacted teeth. Three selected cases were presented as examples of
      the more complex cases in which 3D CT imaging added information not readily
      available from periapical, occlusal, or panoramic radiographs. Patients were CT
      scanned from the occlusal plane to the periapical region of the impacted teeth.
      Digital Image and Communications in Medicine CT data were transferred to a
      personal laptop computer using a network line. 3D volume rendering was performed
      using PC-based volumetric analysis software. 3D CT-reformatted imaging of the
      teeth is a useful way to investigate and localize supernumerary or impacted
      teeth. Newer software that enables this investigation using a PC provides a
      relatively inexpensive way to carry out such investigations, making it easier for
      dental practitioners to request such investigations and to view the results in
      real time in their own offices.

PMID- 14580034
TI  - The management of oromandibular motor disorders and facial spasms with injections
      of botulinum toxin.
AB  - Although much work is yet to be done in this area, nine general conclusions can
      be derived: 1. Local site-of-injection side effects from botulinum toxin
      injections are rare, assuming proper technique is used. 2. The two most common
      medication-related side effects from botulinum toxin orofacial injections are
      alterations in salivary consistency and inadvertent weakness of the swallowing,
      speech, and facial muscles. These complications are injection site-specific (eg,
      more common with lateral pterygoid injections and palatal and tongue muscle
      injections) and dose-dependent problems. These problems are bothersome but are
      not contraindications for the therapy if it is needed. 3. The data presented in
      this article are mostly case series-based and open trial-based information that
      is promising, but randomized, blinded, controlled trials are needed to establish
      the true efficacy of this method for the orofacial motor and pain disorders. 4.
      The novice should begin with injection of muscles he or she can inject with low
      risk of incorrect placement. The hard-to-find muscles should be avoided when
      starting out. The novice clinician should inject and dissect a few cadavers to
      improve injection technique. 5. The general latency for botulinum toxin type A is
      1 week, its duration is 2 to 3 months, and it is recommended that injection be
      done no more than once every 12 weeks to avoid development of antibodies against
      the toxin. 6. Depending on the target muscle, injection dose is 10 to 50 U of
      Botox type A per site with a total dose of 200 U in the masticatory system. More
      than this can be used (400 U maximum) if other sites in the head and neck are
      included in the injection protocol. 7. Regarding injecting painful muscles that
      do not exhibit palpable muscle hardness or EMG-determined spasticity or
      observable involuntary movements but have chronic myofascial trigger points or
      the patient localizes them as the site of their chronic daily headache pain,
      botulinum toxin injections might be helpful used in this manner, but conclusive
      data for this controversial application of botulinum toxin are still missing. 8.
      Hemifacial spasm has the largest number of open-label, clinical trials, some of
      which have a 10-year follow-up. The conclusions reached by all of these reports
      is that treatment of hemifacial spasm with repeated injections of botulinum toxin
      has been highly successful and that the dose and relative effect of the
      injections are stable over time. 9. Although EMG-guided injection may be useful,
      EMG is neither practical nor needed in most situations for orofacial injections
      because most of the orofacial muscles are easily palpable muscles or have
      definitive bony landmarks to help with the localization process.

PMID- 14580035
TI  - Botulinum toxin therapy for cervical dystonia.
AB  - Botulinum toxin revolutionized the treatment of cervical dystonia. In contrast to
      systemically active medications, the effect of botulinum toxin results from
      selective administration to weaken muscles involved in the dystonic posturing of
      the head. This article reviews the pathophysiologic basis of symptoms in cervical
      dystonia and how botulinum toxin alleviates them. Other therapeutic options are
      reviewed for comparison. This article discusses strategies for maximizing the
      clinical benefit of botulinum toxin in this disorder and reviews muscle selection
      and identification with electromyography.

PMID- 14580036
TI  - Botulinum toxin for spasmodic dysphonia.
AB  - Botulinum toxin is the accepted method of managing SD and has given most patients
      with adductor SD the ability to develop satisfactory vocal function. Results have
      been less satisfactory in abductor SD. Management is accomplished best with a
      team approach. The physiatrist with experience in EMG and botulinum toxin usage
      can be a prominent member of this team.

PMID- 14580037
TI  - The importance of electromyographic guidance and electrical stimulation for
      injection of botulinum toxin.
AB  - The importance of EMG or electrical stimulation for guiding injections of
      botulinum toxin in limb muscles to treat dystonia or spasticity is based more on
      theoretical and preclinical data than on controlled clinical trials. Questions
      remain about the preferred administration of botulinum toxin for these
      conditions. Future clinical research is necessary to show clearly functional
      benefit of any particular injection localization method.

PMID- 14580038
TI  - Botulinum toxin in the management of bowel and bladder function in spinal cord
      injury and other neurologic disorders.
AB  - Botulinum toxin inhibits release of acetylcholine and other neurotransmitters. It
      has been used successfully to treat pain and abnormal skeletal and smooth muscle
      activity in patients. This article discusses its use in patients with bladder and
      bowel disorders.

PMID- 14580039
TI  - Botulinum toxins in pain management.
AB  - BTs are a useful treatment in refractory MPS and have shown promise in various
      superficial neuropathic pain syndromes. Presumably BTs work by breaking the
      spasm/pain cycle, giving the patient a "window of opportunity" for traditional
      conservative measures to have a greater beneficial impact, but several studies
      suggest that a direct antinociceptive effect distinct from any reduction in
      muscle spasm may be at play. The major benefit of BTs compared with standard
      therapies is duration of response. BTs cannot be considered a "first line"
      treatment for any pain application; however, in refractory cases in which nothing
      else has helped, BTs may offer the patient and physician a chance for improvement
      and perhaps even cure.

PMID- 14580040
TI  - Use of botulinum toxin type A and type B for spasticity in upper and lower limbs.
AB  - BT is likely effective in controlling spasticity in the smaller muscles of the
      arm and hand, although there has been only one large controlled trial. For lower
      limb spasticity, the outcomes are more mixed. No large randomized, controlled
      trials have been done, and the larger size of the muscles results in a decreased
      ability to treat widespread spasticity. For more focal treatment in the legs and
      feet, however, and when combined with other denervating agents or physical
      modalities, BT is probably effective. Careful analysis is warranted before
      performing any chemodenervation on a limb muscle or muscles.

PMID- 14580041
TI  - Treatment of hyperhidrosis and drooling with botulinum exotoxin.
AB  - The treatment of focal hyperhidrosis and drooling with neurolysis of the
      neuroglandular junction is a relatively new and useful technique for managing
      such obvious conditions and improving the patient's quality of life. The
      treatment is safe, minimally invasive, and an effective alternative to other
      treatment modalities.

PMID- 14580042
TI  - Muscle overactivity and movement dysfunction in the upper motoneuron syndrome.
AB  - The upper motoneuron syndrome (UMN) is a collective term that refers to different
      types of motor behaviors produced by patients who have lesions of the descending
      corticospinal system. Lesions involving the upper motoneuron, its pathways, and
      its connections can occur at the level of the cortex, internal capsule, brain
      stem, or spinal cord. The clinical features of UMN have traditionally been
      classified as "positive" phenomena, referring to overt behaviors generated by
      various forms of muscle overactivity, and "negative" phenomena, referring to loss
      of overt behaviors secondary to impaired muscle activation, impaired control of
      motor behavior, and impaired motor performance. The clinical impact of UMN on
      patients is broad and tends to limit functional capacity. The negative and
      positive signs lead to reduced mobility and limb usage.

PMID- 14580043
TI  - Botulinum toxins in the treatment of migraine and tension-type headaches.
AB  - Botulinum toxins are promising preventive treatments for patients with moderate
      to severe episodic and chronic migraine and chronic daily headache. The
      recommended indications for botulinum toxins as preventive therapy lend
      themselves to the following patient types: those who demonstrate a lack of
      improvement from preventive (prophylactic) pharmacotherapy; those who experience
      severe and intolerable adverse events from preventive medications; those who
      refuse to use daily medications; those who have contraindications to acute
      migraine therapy, and elderly patients with chronic migraine. Both open-label and
      double-blind placebo-controlled studies using fixed-site, "follow the pain." or a
      combination approach have demonstrated significant reduction in migraine
      frequency, severity, and duration, as well as decreased use of acute medications.
      The most prominent reductions have been noted in those with reportedly the most
      severe migraine headaches. Large, well-designed, double-blind, placebo-controlled
      studies are recommended to further clarify optimum dosage and location of
      injection, reduce treatment frequency and duration, and address other primary
      headache disorders that may benefit from this therapy.

PMID- 14580044
TI  - Spinal cord injury and use of botulinum toxin in reducing spasticity.
AB  - Spasticity is commonly seen after spinal cord injury, and a large percentage of
      patients with spinal cord injury will need treatment to control it. Although oral
      medications do a fair job of controlling spasticity in most patients, some
      patients will need additional forms of treatment. In many cases, oral medications
      alone do not adequately control spasticity or the patient cannot tolerate the
      side effects. In these instances, botulinum toxin may help control the spasticity
      for approximately 3 months after injection. The amount of botulinum toxin and the
      injection sites can be tailored to meet individual patient needs. Botulinum
      toxins can reduce spasticity, improve function, and reduce the amount of needed
      assistance.

PMID- 14580045
TI  - SESAM--the Society in Europe for Simulation Applied to Medicine.

PMID- 14580046
TI  - Strategies to reduce perioperative blood loss related to non-surgical bleeding.
AB  - The treatment of critically ill patients has advanced markedly over the last
      decade. However, non-surgical bleeding of a diffuse nature from numerous tiny
      capillaries still remains a challenge. Once initiated, this type of bleeding may
      be troublesome and a vicious circle develops since it is not a single vessel
      contributing to this blood loss. The description 'non-surgical blood loss' is
      often given to this. This review describes a step-by-step approach for the
      treatment of non-surgical bleeding and includes various measures, such as
      desmopressin, blood components, antifibrinolytics, antithrombin III, prothrombin
      complex concentrates and factor XIII. While most non-surgical bleedings can be
      managed using the approach described here, a number of patients still continue to
      bleed. In these cases, the surgeon should re-evaluate the bleeding in terms of
      its surgical origin. If this can positively be excluded and if all of measures
      described fail to reduce or stop the bleeding, further treatment of such
      uncontrolled bleeding remains symptomatic.

PMID- 14580047
TI  - Albumin administration--what is the evidence of clinical benefit? A systematic
      review of randomized controlled trials.
AB  - BACKGROUND AND OBJECTIVE: The advantages of albumin over less costly alternative
      fluids continue to be debated. Meta-analyses focusing on survival have been
      inconclusive, and other clinically relevant end-points have not been
      systematically addressed. We sought to determine whether albumin confers
      significant clinical benefit in acute illness compared with other fluid regimens.
      METHODS: Database searches (MEDLINE, EMBASE, Cochrane Library) and other methods
      were used to identify randomized controlled trials comparing albumin with
      crystalloid, artificial colloid, no albumin or lower-dose albumin. Major findings
      for all end-points were extracted and summarized. A quantitative meta-analysis
      was not attempted. RESULTS: Seventy-nine randomized trials with a total of 4755
      patients were included. No significant treatment effects were detectable in 20/79
      (25%) trials. In cardiac surgery, albumin administration resulted in lower fluid
      requirements, higher colloid oncotic pressure, reduced pulmonary oedema with
      respiratory impairment and greater haemodilution compared with crystalloid and
      hydroxyethylstarch increased postoperative bleeding. In non-cardiac surgery,
      fluid requirements, and pulmonary and intestinal oedema were decreased by albumin
      compared with crystalloid. In hypoalbuminaemia, higher doses of albumin reduced
      morbidity. In ascites, albumin reduced haemodynamic derangements, morbidity and
      length of stay and improved survival after spontaneous bacterial peritonitis. In
      sepsis, albumin decreased pulmonary oedema and respiratory dysfunction compared
      with crystalloid, while hydroxyethylstarch induced abnormalities of haemostasis.
      Complications were lowered by albumin compared with crystalloid in burn patients.
      Albumin-containing therapeutic regimens improved outcomes after brain injury.
      CONCLUSIONS: Albumin can bestow benefit in diverse clinical settings. Further
      trials are warranted to delineate optimal fluid regimens, in particular
      indications.

PMID- 14580048
TI  - Derecruitment of the lung induced by stepwise lowering of positive end-expiratory
      pressure in patients with adult respiratory distress syndrome.
AB  - BACKGROUND AND OBJECTIVE: It has recently been suggested that recruitment
      proceeds far above the lower inflection point of the elastic pressure-volume
      (Pel/V) curve of the respiratory system. Accordingly, the value of the lower
      inflection point as a guide to set the positive end-expiratory pressure (PEEP)
      has been challenged. Our aim was to evaluate the derecruitment induced by
      stepwise decreasing PEEP levels. METHODS: Seven consecutive sedated and paralysed
      patients with acute respiratory distress syndrome were studied. Multiple Pel/V
      curves of the respiratory system were recorded at PEEP levels progressively
      decreasing in steps of 3.75 cmH2O from + 15 to zero according to the principles
      of the low flow inflation method. RESULTS: Multiple Pel/V curves shifted towards
      lower volumes at decreasing PEEP. Dynamic compliance was higher for Pel/V curves
      recorded from lower PEEP levels. A high correlation (r = 0.99) was found between
      dynamic compliance and PEEP. The lower inflection point was on average 9.2 cmH2O.
      However, the transition between the lower segment and the linear part of the
      Pel/V curve was in general smooth to the eye. The upper inflection point was on
      average 23.8 cmH2O. A high correlation (r = 0.98) between the upper inflection
      point and PEEP was found. CONCLUSIONS: The lower inflection point is a poor
      indicator of alveolar closure. The evaluation of derecruitment induced by a
      stepwise reduction in PEEP seems to be more useful than individual titration of
      PEEP and tidal volume in patients with adult respiratory distress syndrome.

PMID- 14580049
TI  - Excitatory effects of fentanyl upon the rat electroencephalogram and auditory
      evoked potential responses during anaesthesia.
AB  - BACKGROUND AND OBJECTIVE: Previous studies have shown existence of inconsistent
      data concerning the use of auditory-evoked potential (AEP) and
      electroencephalogram (EEG) changes to measure the depth of anaesthesia in
      regimens involving the use of opioids. The present studies characterize the
      effects of fentanyl on those responses in rats. METHODS: The effects of a bolus
      of fentanyl (6-10 microg kg(-1) intravenously) alone or following naloxone (100
      microg kg(-1) intravenously) were examined using brain responses in rats during
      light anaesthesia with either propofol (20-30 mg kg(-1) h(-1)) or isoflurane
      (0.8%). Electrophysiological data were recorded using silver ball electrodes. The
      rats' tracheas were intubated and a femoral artery cannula was inserted to
      monitor blood pressure. Body temperature, respiratory and pulse rate, and pedal
      withdrawal data were also collected. Parameters measured before and following
      administration of naloxone and fentanyl or of fentanyl alone were compared using
      repeated-measures ANOVA. RESULTS: Fentanyl significantly increased the latency of
      the major peak from the AEP during propofol and isoflurane anaesthesia (F = 13.2
      and 13.5, respectively; P < 0.05) and the amplitude differential between two
      waveform complexes, and the second differential index (F = 28.3 and 57.2,
      respectively; P < 0.01). The spectral edge frequency and median frequency from
      the EEG tended to increase. These effects were abolished by the prior
      administration of naloxone. CONCLUSIONS: These excitatory effects were
      inconsistent with the classical concept of brain activity depression indicating a
      deepening of anaesthesia.

PMID- 14580050
TI  - Effects of nicardipine and diltiazem on the bispectral index and 95% spectral
      edge frequency.
AB  - BACKGROUND AND OBJECTIVE: Previous studies have shown that L-type voltage
      sensitive Ca2+ channel blocking agents increased and the L-type Ca2+ channel
      activator Bay K 8644 reduced the general anaesthetic potency in animals. As the
      bispectral index correlates with the depth of sedation, we examined whether L
      type Ca2+ channel blocking agents affect the bispectral index. METHODS: Thirty
      hypertensive patients (systolic arterial pressure >160 mmHg) presenting for total
      intravenous anaesthesia with propofol, fentanyl and ketamine were recruited.
      Bispectral index monitoring was commenced directly the patients arrived in the
      operating theatre. All patients were given either nicardipine or diltiazem
      intravenously at the discretion of the anaesthesiologist in charge. RESULTS:
      Twenty-three and seven patients received nicardipine or diltiazem, respectively.
      The bispectral index level (mean (95% confidence interval)) did not change with
      either drug. In the nicardipine group, the bispectral index at 0, 5, 10 and 15
      min was 55 (52-58), 55 (51-59), 55 (52-59) and 56 (53-59), respectively. In the
      diltiazem group, values were 59 (48-71), 60 (51-70), 61 (52-71) and 61 (50-72),
      respectively. Both L-type Ca2+ channel blocking agents significantly decreased
      arterial pressure. CONCLUSIONS: Clinical doses of nicardipine and diltiazem do
      not alter the bispectral index during general anaesthesia.

PMID- 14580051
TI  - Remifentanil-propofol versus sufentanil-propofol anaesthesia for supratentorial
      craniotomy: a randomized trial.
AB  - BACKGROUND AND OBJECTIVE: Remifentanil has unique pharmacokinetics that might
      allow faster recovery after neurosurgery. We investigated the effects of a
      propofol/sufentanil versus a remifentanil/propofol regimen on the primary end
      point tracheal extubation time. METHODS: In the Neurosurgery Department of a
      University Hospital, 36 patients awaiting craniotomy for supratentorial tumour
      resection were randomly assigned to one of two study groups. In the
      sufentanil/propofol group, anaesthesia was induced with 0.5 microg kg(-1)
      sufentanil and 1-2 mg kg(-1) propofol. Propofol infusion and boluses of
      sufentanil were administered for maintenance. In the remifentanil/propofol group,
      anaesthesia was started with an infusion of remifentanil (0.2-0.35 microg kg(-1)
      min(-1)) and a bolus of propofol (1.5-2 mg kg(-1)). Patients received a propofol
      infusion and a remifentanil infusion for maintenance of anaesthesia. Recovery
      times were taken from cessation of the propofol infusion. In addition, data about
      self-reported nausea and vomiting, pain and analgesic requirements were
      collected. RESULTS: Patients in the remifentanil/propofol group were extubated
      earlier (mean times 6.4 (+/- SD 4.7) versus 14.3 (+/- 9.2) min; P = 0.003). The
      two groups were similar with respect to postoperative nausea and vomiting, and
      patient-reported pain scores. Fifty per cent of the remifentanil/propofol
      patients and 88% of the sufentanil/propofol patients required no analgesics
      within 1 h after operation (P = 0.03). CONCLUSIONS: The remifentanil/propofol
      regimen provided quicker recovery. The two regimens were similar in terms of
      postoperative nausea and vomiting and patient-reported pain scores, but patients
      in the remifentanil/ propofol group required more analgesics within 1 h
      postoperatively.

PMID- 14580052
TI  - Neuromuscular block and relative concentrations of mivacurium isomers under
      isoflurane versus propofol anaesthesia.
AB  - BACKGROUND AND OBJECTIVE: The augmentation of the effect of neuromuscular
      blocking drugs with volatile anaesthetics is well documented, but the mechanism
      remains unclear. The pharmacological interaction and relative plasma
      concentrations of mivacurium isomers were investigated during either propofol- or
      isoflurane-maintained anaesthesia. METHODS: Forty-four patients were randomly
      assigned to one of two groups: isoflurane or propofol. All patients received an
      initial dose of mivacurium 0.1 mg kg(-1). After recovery of the first twitch (T1)
      response measured by acceleromyography to 5%, a T1 depression of 90-99% was
      maintained by infusion. After a steady state was reached, blood samples were
      taken after 10 and 30 min for analysis of mivacurium isomers. Recovery times for
      T1 to 251/50/75/90% (TW25-90), train-of-four ratio 25/70% and recovery index
      (time TW25-75) were recorded after stop of infusion. RESULTS: In the isoflurane
      group, lower infusion rates were needed (3.0 +/- 1.6 versus 3.6 +/- 1.6 microg
      kg(-1) min(-1)) and there was a slower recovery (significant for train-of-four
      ratio 70%: 21.9 versus 17.9 min). The plasma concentrations of mivacurium and its
      trans-trans isomer (in percentage of the total) were significantly higher in the
      isoflurane group (10 min: 52.6 versus 25.8%; 30 min: 49.6 versus 23.2%).
      CONCLUSIONS: For mivacurium, the phenomenon of 'potentiation' of the effect of
      muscle relaxants by volatile anaesthetics could be due to an increase in the
      plasma concentration of the potent trans-trans isomer.

PMID- 14580053
TI  - Levobupivacaine 0.25% compared with ropivacaine 0.25% by the caudal route in
      children.
AB  - BACKGROUND AND OBJECTIVE: Levobupivacaine is the most recently introduced local
      anaesthetic into clinical practice. In a randomized double-blinded study, the
      onset, intraoperative tolerance, postoperative analgesic effect, motor blockade
      and any adverse reactions produced by levobupivacaine were compared with
      ropivacaine. METHODS: Sixty children, ASA I-II, 2-6 yr old, undergoing elective
      minor surgery, received a single caudal injection of 1 mL kg(-1) of either
      levobupivacaine 0.25% or ropivacaine 0.25%. Caudal blocks were performed after
      induction of inhalation general anaesthesia using sevoflurane; anaesthesia was
      maintained via a laryngeal mask airway using a mixture of sevoflurane, oxygen and
      air. RESULTS: Onset time, intraoperative tolerance, postoperative analgesic
      effect and motor blockade were comparable between the two groups. The mean onset
      of the block was 8.2 +/- 2.2 min for levobupivacaine and 8.5 +/- 3.0 min for
      ropivacaine (P = 0.66). Additional analgesics during operation were not required
      in any of the children. No significant difference was found for mean time to
      requirement of additional analgesia with rectal acetaminophen (paracetamol) (302
      +/- 29 min for the levobupivacaine group and 230 +/- 38 min for the ropivacaine
      group (P = 0.32)). During the first 4 h after placement of caudal block, the pain
      assessment score (according to the Children Hospital Eastern Ontario Pain Scale)
      was comparable for the two groups. No motor block was observed in any group on
      awakening, nor during the observation period. CONCLUSIONS: We conclude that
      levobupivacaine 0.25% 1 mL kg(-1) provides caudal block of comparable onset and
      duration, as produced by the same volume and concentration of ropivacaine.

PMID- 14580055
TI  - Do we know all about hypothermia and are studies on the subject unethical?

PMID- 14580054
TI  - Comparison of oral dolasetron and ondansetron in the prophylaxis of postoperative
      nausea and vomiting in children.
AB  - BACKGROUND AND OBJECTIVE: In a randomized, placebo-controlled, double-blind
      trial, we compared the efficacy of oral dolasetron and ondansetron in preventing
      postoperative nausea and vomiting in children after various surgical operations.
      METHODS: Children were assigned randomly to one of three groups (each contained
      50 children) to receive dolasetron 1.8 mg kg(-1) or ondansetron 0.15 mg kg(-1)
      orally, or a placebo. All children received methylene blue capsules (10 mg)
      orally as an indicator before the induction of anaesthesia. Postoperatively,
      contamination of the mouth and the endotracheal tube by methylene blue was
      recorded, and postoperative nausea and vomiting was recorded for 0-1, 1-24 and 0
      24 h. Metoclopramide (0.1 mg kg(-1)) intravenously was used as the rescue
      antiemetic. RESULTS: In the 0-1 h period after operation, there were no
      differences between the groups. In the 1-24 h period, dolasetron was
      significantly better than placebo (nausea 8 versus 24%; vomiting 4 versus 20%;
      total nausea and vomiting scores 16 versus 48%). Over the 0-24 h period, both
      dolasetron and ondansetron were significantly better than placebo (nausea 16
      versus 26 versus 40%), vomiting (8 versus 16 versus 30%), and total nausea and
      vomiting scores (32 versus 48 versus 78%). There were no significant differences
      between dolasetron and ondansetron. There was no important methylene blue
      contamination, and little use of rescue metoclopramide. There were no important
      adverse events. CONCLUSIONS: Prophylactic oral dolasetron and ondansetron were
      effective in reducing postoperative nausea and vomiting in children.

PMID- 14580056
TI  - No variation for Wolbachia-induced hybrid breakdown in two populations of a
      spider mite.
AB  - Wolbachia are cytoplasmically transmitted bacteria that infect several species of
      mites. In the two-spotted spider mite Tetranychus urticae Koch this symbiont can
      induce reproductive incompatibility. Wolbachia-induced reproductive
      incompatibility is observed in crosses between Wolbachia-infected (W) males and
      uninfected (U) females. This incompatibility is expressed in F1 broods as male
      biased sex ratios, an effect called cytoplasmic incompatibility (CI). However, in
      the two-spotted spider mite, Wolbachia-induced reproductive incompatibility may
      extend to the F2: broods of virgin F1 females from U x W crosses sometimes suffer
      increased mortality rates. This F2 effect is called hybrid breakdown (HB).
      Several isofemale lines derived from mites collected from rose and cucumber
      plants had been previously tested for CI. Here we report on the results obtained
      for HB.

PMID- 14580057
TI  - Intraspecific variation in induction of feeding preference and performance in a
      herbivorous mite.
AB  - Induction of food preference has often been observed in herbivorous insects. The
      term is used to indicate preference of individuals for the host plant they have
      already experienced over one they have not experienced. A typical set-up is one
      where individuals first feed on host X or Y, and are then offered a choice
      between host X and Y. This set-up--and hence the body of empirical data--has been
      criticised for lack of a control treatment to untangle the effects of the
      separate hosts. In this study, we use a design with a third, unrelated host as
      control to investigate induction of preference in the herbivorous arthropod,
      Tetranychus urticae. We provide evidence of induced preference, as well as
      induced performance, and show that there is considerable variation in these two
      traits among strains. We suggest induced resistance to toxic secondary plant
      chemicals as one potential explanation for induced performance. This in itself
      suggests associative learning as the most likely candidate learning mechanism for
      induction of preference in this species. Phenotypically plastic effects
      underlying induced performance may be a general aspect of induction of preference
      in herbivorous arthropods, which warrants closer attention to these phenomena.

PMID- 14580058
TI  - Acarine regulators of water hyacinth in Kerala (India).
AB  - Screening of the mite fauna on water hyacinth, Eichhornia crassipes, at 25
      localities throughout Kerala (India) yielded a list of 21 phytophagous species
      from nine families. Distribution of mites at these localities and type of injury
      produced suggested that Oligonychus biharensis and Orthogalumna terebrantis
      warrant further study. In an experimental set-up the injury caused by these mites
      was quantified. Infestation by Ol. biharensis lead to reduced photosynthesis by
      the host (significant loss in chlorophyll content). Injurious effects of Or.
      terebrantis involved leaf mining by the developing instars leading to wilting of
      the leaves resulting in reduced dry weight. The relative merits of the two
      species as potential control agents of water hyacinth are discussed.

PMID- 14580059
TI  - Interactions in a tritrophic acarine predator-prey metapopulation system V:
      within-plant dynamics of Phytoseiulus persimilis and Tetranychus urticae (Acari:
      Phytoseiidae, Tetranychidae).
AB  - To investigate the relative contributions of bottom-up (plant condition) and top
      down (predatory mites) factors on the dynamics of the two-spotted spider mite
      (Tetranychus urticae), a series of experiments were conducted in which spider
      mites and predatory mites were released on bean plants. Plants inoculated with 2,
      4, 8, 16, and 32 adult female T. urticae were either left untreated or were
      inoculated with 3 or 5 adult female predators (Phytoseiulus persimilis) one week
      after the introduction of spider mites. Plant area, densities of T. urticae and
      P. persimilis, and plant injury were assessed by weekly sampling. Data were
      analysed by a combination of statistical methods and a tri-trophic mechanistic
      simulation model partly parameterised from the current experiments and partly
      from previous data. The results showed a clear effect of predators on the density
      of spider mites and on the plant injury they cause. Plant injury increased with
      the initial number of spider mites and decreased with the initial number of
      predators. Extinction of T. urticae, followed by extinction of P. persimilis, was
      the most likely outcome for most initial combinations of prey and predators. Eggs
      constituted a relatively smaller part of the prey population as plant injury
      increased and of the predator population as prey density decreased. We did not
      find statistical evidence of P. persimilis having preference for feeding on T.
      urticae eggs. The simulation model demonstrated that bottom-up and top-down
      factors interact synergistically to reduce the density of spider mites. This may
      have important implications for biological control of spider mites by means of
      predatory mites.

PMID- 14580060
TI  - Mites as selective fungal carriers in stored grain habitats.
AB  - Mites are well documented as vectors of micromycetes in stored products. Since
      their vectoring capacity is low due to their small size, they can be serious
      vectors only where there is selective transfer of a high load of specific fungal
      species. Therefore the aim of our work was to find out whether the transfer of
      fungi is selective. Four kinds of stored seeds (wheat, poppy, lettuce, mustard)
      infested by storage mites were subjected to mycological analysis. We compared the
      spectrum of micromycete species isolated from different species of mites (Acarus
      siro, Lepidoglyphus destructor, Tyrophagus putrescentiae, Caloglyphus
      rhizoglyphoides and Cheyletus malaccensis) and various kinds of stored seeds.
      Fungi were separately isolated from (a) the surface of mites, (b) the mites'
      digestive tract (= faeces), and (c) stored seeds and were then cultivated and
      determined. The fungal transport via mites is selective. This conclusion is
      supported by (i) lower numbers of isolated fungal species from mites than from
      seeds; (ii) lower Shannon-Weaver diversity index in the fungal communities
      isolated from mites than from seeds; (iii) significant effect of mites/seeds as
      environmental variables on fungal presence in a redundancy analysis (RDA); (iv)
      differences in composition of isolated fungi between mite species shown by RDA.
      The results of our work support the hypothesis that mite-fungal interactions are
      dependent on mite species. The fungi attractive to mites seem to be dispersed
      more than others. The selectivity of fungal transport via mites enhances their
      pest importance.

PMID- 14580061
TI  - Trophic determinants of hypopus induction in the stored-product mite
      Lepidoglyphus destructor (Acari: Astigmata).
AB  - A unique (synapomorphic) characteristic of astigmatic mites is the heteromorphic
      deuteronymph also called hypopus. It is a non-feeding and facultative instar
      between protonymph and tritonymph. The hypopus is adapted for dispersal and
      sometimes also for dormancy, as in Lepidoglyphus destructor. The experiments
      reveal a correlation between the composition of the foodstuff, the duration of
      development of homomorphic instars, the mortality of protonymphs and the
      production of hypopodes. As food quality decreases, development lasts longer,
      mortality increases and hypopodes are produced in greater numbers.
      Disadvantageous trophic conditions of varied chemical nature favour the induction
      of hypopodes. The experimental data show that hypopus incidences (as percentage
      individuals of a population) depend on the relative proportions of constituents
      of an ingested foodstuff. What matters is the ratio between nourishing foodstuff
      components and those that are of little or no nutritional value. When a certain
      ratio does not meet a presumed metabolically required level of nutrients a
      nutritional deficiency results and hypopus induction is triggered, provided that
      adequate genetic propensities for hypopus production are present (L. destructor
      is highly polymorphic for hypopus production). Specific key substances are
      apparently not involved, and composite properties of a foodstuff are crucial for
      hypopus induction. Decrease of food quality (not poor food per se) during the
      hypopus-inducible period (late larval to early protonymphal phase) promotes
      hypopus induction. The interpretation matches the ecological scene. When trophic
      deterioration of a patch habitat sets in, often as a result of overcrowding,
      conditions will eventually become untenable. As a response to incurring
      nutritional deficiencies the mites will induce hypopodes, which provide for
      escape from or survival at the decaying habitat patch. Experiments support the
      threshold model of quantitative genetics for hypopus expression as previously
      inferred from other experiments with L. destructor.

PMID- 14580062
TI  - Heritability of male morph in the bulb mite, Rhizoglyphus robini (Astigmata,
      Acaridae).
AB  - In several species of Acaridae (Astigmata), heteromorphic males, possessing a
      sharply terminated third pair of legs which they use to mortally stab other
      males, coexist with scrambler males with unmodified legs. Previous research
      showed that in the bulb mite, Rhizoglyphus robini (Claparede), the male morph is
      heritable. In this study I used a different population and carried out selection
      in both downward and upward direction in order to change the proportion of
      morphs. Starting from the proportion of about 0.2 homeomorphs in the population,
      I obtained a significant response to 8-10 generations of selection in two
      repetitions. The response was asymmetrical (stronger in upward direction).
      Realised heritabilities were in the range of 0.3 (downward) and 0.8 (upward).

PMID- 14580063
TI  - Potentiation of a propargite and fenpyroximate mixture against two-spotted spider
      mite, Tetranychus urticae (Acari: Tetranychidae).
AB  - Using susceptible and resistant reference strains and standard bioassay methods a
      new miticide product was screened for efficacy and cross-resistance against two
      spotted spider mite, Tetranychus urticae Koch. Experimental product NN1 850.0 EW
      (fenpyroximate and propargite 3:10 ratio) was significantly (P<0.05) more toxic
      than either compound tested alone (co-toxicity index 1029). Non-overlapping 95%
      CIs at the LC50 and LC99 level suggest that there is no cross-resistance to NN1
      850.0 EW from existing organophosphate and pyrethroid resistance. NN1 850.0 EW is
      worthy of further development for T. urticae control.

PMID- 14580064
TI  - Attraction of Amblyomma variegatum (ticks) to the attraction-aggregation
      attachment-pheromone with or without carbon dioxide.
AB  - The responses of adult Amblyomma variegatum ticks released from various distances
      to different doses of the synthetic attraction-aggregation-attachment pheromone
      (AAAP) (made up of orthonitrophenol, methyl salicylate and nonanoic acid in
      paraffin oil), dispensed from the center of circular field plots, were studied in
      the presence or absence of elevated levels of CO2. Up to 90% of the ticks
      released were attracted to the pheromone source in the presence of CO2 within 3h.
      CO2 alone was unattractive, similar to previous findings in Zimbabwe, but unlike
      results from a Caribbean A. variegatum population, which was significantly
      attracted to this signal. In the absence of CO2, smaller but significant
      proportions of the released ticks were attracted to the pheromone, albeit more
      slowly, suggesting another variation in the responses of this bont tick to inter-
      and intra-specific signals. Our results are interpreted in the light of a study
      undertaken elsewhere demonstrating relatively high heterozygosity among tick
      populations. Possible directions of further research to explore the use of the
      pheromone in off-host control of the tick are also highlighted.

PMID- 14580065
TI  - Hosts and distribution of Amblyomma auricularium (Conil 1878) and Amblyomma
      pseudoconcolor Aragao, 1908 (Acari: Ixodidae).
AB  - Collections of Amblyomma auricularium (Conil 1878) and A. pseudoconcolor Aragao,
      1908 are discussed in relation to distribution and hosts. Three tick collections
      (two from Argentina and a third from the USA) house a total of 574 A.
      auricularium (307 males, 162 females, 73 nymphs and 32 larvae) and 179 A.
      pseudoconcolor (96 males, 74 females, 4 nymphs and 5 larvae). Apart from an adult
      A. pseudoconcolor found on a bird, Nothura maculosa Temminck, 1815, all ticks
      were found on mammals. The great majority of specimens of both ticks species were
      removed from the family Dasypodidae Gray, 1821 (84.9% and 93.8% of A.
      auricularium and A. pseudoconcolor, respectively). Amblyomma auricularium has
      also been found on wild hosts of the families Myrmecophagidae and occasionally
      Didelphidae, Caviidae, Chinchillidae, Hydrochaeridae, Muridae, Canidae,
      Mustelidae, Procyonidae and domestic animals (cattle, dogs, horses), while A.
      pseudoconcolor has also been found occasionally on wild hosts of the family
      Didelphidae and on domestic animals (cattle, dogs). Amblyomma pseudoconcolor
      appears to be restricted to the Neotropical region, covering northern Argentina
      and the eastern region of South America from Uruguay to Surinam, including south
      eastern Paraguay, eastern Brazil and French Guiana. Amblyomma auricularium is
      distributed from northern Patagonia in Argentina throughout the Neotropics into
      the Nearctic region up to the southern USA (Texas, Florida), with collection
      localities also in Belize, Bolivia, Brazil, Colombia, Costa Rica, French Guiana,
      Honduras, Mexico, Nicaragua, Panama, Paraguay, Trinidad & Tobago, Uruguay and
      Venezuela. It is not known whether A. auricularium is an established resident of
      the USA.

PMID- 14580066
TI  - Immunity against Boophilus annulatus induced by the Bm86 (Tick-GARD) vaccine.
AB  - Friesian cattle were immunized with two inoculations of anti-tick Bm86 (Tick
      GARD) vaccine and were challenged 30 or 90 d later with Boophilus annulatus
      larvae derived from 1.2 g of eggs. No nymphs or adult ticks were found on the
      immunized cattle during four weeks after challenge. Repeated infestations (2 to
      4) with larvae on three other calves during a period of 160 and 390 d after the
      immunization did not result in development of nymphal and adult stages. In
      control, non-immunized cattle infested with corresponding batches of larvae 1380
      to 4653 replete adult female ticks were collected. Larvae issued from Babesia
      bovis-infected female ticks transmitted the infection to Bm86-immunized cattle,
      but the progeny of B. bigemina-infected females did not. Since B. bigemina is
      transmitted exclusively by nymphal stages of Bo. annulatus these results support
      the observation that immunity induced by Bm86 affects the larval stage of this
      tick.

PMID- 14580068
TI  - Life events: effects and genesis.

PMID- 14580067
TI  - Three serine proteinases from midguts of the hard tick Rhipicephalus
      appendiculatus; cDNA cloning and preliminary characterization.
AB  - Rhipicephalus appendiculatus is one of the most economically important ticks
      distributed in south central and eastern Africa where little or no progress has
      been made on attempts to develop a vaccine. We have used a combination of RT-PCR,
      the 3' and 5'rapid amplification of cDNA ends (RACE) to clone and sequence three
      cDNAs encoding full-length R. appendiculatus midgut serine proteinases (RAMSP).
      RT-PCR degenerate primers were designed from amino acid sequences surrounding
      active sites, His57 and Ser195 conserved among most known serine proteinase-like
      genes (Mulenga et al. 2001). Northern blotting analysis of total RNA extracted
      from unfed and partially fed adult ticks revealed that mRNAs for RAMSP-1 and -2
      were expressed only in partially fed ticks, while RAMSP-3 mRNA was not only
      expressed in both unfed and partially fed ticks, it was also up-regulated as tick
      feeding progressed. Expression analysis by RT-PCR revealed that RAMSP-3 was
      predominantly expressed in midguts when compared to salivary glands. For RAMSP-1
      and -2, they were expressed at equivalent levels in both midguts and salivary
      glands. Based on key amino acid sequence features as well as similarity
      comparisons from the database, we speculated that polypeptides encoded by RAMPSP
      1 to -3 are structurally more closely related to chymotrypsin- than trypsin-like
      serine proteinases. We have based our comments on the potential of serine
      proteinases as candidates for tick vaccines.

PMID- 14580069
TI  - How often do patients with psychosis fail to adhere to treatment programmes? A
      systematic review.
AB  - BACKGROUND: Studies that assess the rates of psychotic patients who fail to
      adhere to treatment programmes have generated heterogeneous results, with
      estimates ranging from 24 to 90%. This paper presents findings from a systematic
      review on adherence to treatment by patients with psychosis. Its purpose is to
      provide an overall estimate of treatment non-adherence in community psychiatric
      services, and to analyse and study patient characteristics explaining the between
      study heterogeneity in rates of non-adherence. METHOD: A systematic review of
      published studies that report rates of non-adherence with medication and
      scheduled appointments by psychotic patients in community settings has been
      undertaken. RESULTS: A total of 103 studies were included in this systematic
      review. Eighty-six of these studies were suitable for data re-analysis. The
      overall weighted mean rate of non-adherence, calculated in a sample of 23 796
      patients, was 25.78%. A linear regression analysis of non-adherence rates on
      background characteristics showed that sample size was negatively associated with
      non-adherence rates, while first-contact cases and low-adherence cases, in
      comparison with ongoing cases, were associated with higher non-adherence rates.
      Factors associated with poor compliance included: lack of insight; positive
      symptoms; younger age; male gender; history of substance abuse; unemployment; and
      low social functioning. CONCLUSIONS: Approximately one in four patients with
      psychosis fails to adhere with treatment programmes. Preventive evidence-based
      clinical interventions should be routinely implemented in community settings to
      reduce patient non-adherence.

PMID- 14580070
TI  - Life events, social support and depression in childbirth: perspectives from a
      rural community in the developing world.
AB  - BACKGROUND: High rates of depression associated with childbirth have been
      reported in many parts of the developing world. However, the prevalence and
      associations of antenatal and post-natal depression in the rural population
      remain unknown. Disability associated with depression and its impact on infant
      health and development could have important public health implications for many
      developing countries where large proportions of the population are rural. METHOD:
      All women living in southern Kahuta, Pakistan, in their third trimester of
      pregnancy were interviewed at 6 weeks before delivery (N = 632) and again at 10
      12 weeks after delivery (N = 541), using WHO Schedule for Clinical Assessment in
      Neuropsychiatry (SCAN), Personal Information Questionnaire (PIQ) and Brief
      Disability Questionnaire (BDQ). RESULTS: The point prevalence of ICD-10
      depressive disorder was 25% in the antenatal period and 28 % in the post-natal
      period. Depressed mothers were significantly more disabled, had more threatening
      life events, and poorer social and family support than non-depressed mothers.
      Vulnerable mothers were more likely to be depressed during pregnancy, rather than
      have an onset in the post-natal period. CONCLUSION: Over one-quarter of mothers
      in a rural sub-district of Pakistan suffer from depression shortly before and
      after childbirth. Rapidly changing traditional family structures and practices
      may be increasing the risk of depression in many women. Recognizing and treating
      depression should be initiated during the antenatal, rather than post-natal
      period.

PMID- 14580072
TI  - Does the impact of major stressful life events on the risk of developing
      depression change throughout life?
AB  - BACKGROUND: It is unclear whether there is an interaction of ageing on the
      association between major life events and onset of depression. METHOD: This was a
      population-based nested case-control study with linkage of the Danish Psychiatric
      Central Research Register and the Integrated Database for Longitudinal Labour
      Market Research. The study includes data on all admissions at psychiatric wards
      in Denmark from 1981 to 1998 and data on sociodemographic variables and
      death/suicide of first-degree relatives. RESULTS: A total of 13 006 patients who
      received a diagnosis of depression at the first ever admission at a psychiatric
      ward and a gender- and age-matched control group of 260 108 subjects were
      identified. A recent divorce and recent unemployment and suicide of a relative
      (mother, father, sibling, child, spouse) were associated with increased risk of
      being admitted for the first time ever at a psychiatric ward with a diagnosis of
      depression whereas death of a relative by causes other than suicide had no
      significant effect. In general, no interaction was found with age with any of the
      variables, totally, or for men or women, separately. CONCLUSIONS: The
      susceptibility to major life stressors does not seem to change throughout life.

PMID- 14580071
TI  - Humiliation, loss and other types of life events and difficulties: a comparison
      of depressed subjects, healthy controls and their siblings.
AB  - BACKGROUND: It has been proposed that adverse life events involving loss or
      humiliation are particularly potent in provoking depressive episodes. We have
      also previously suggested that experiencing high rates of non-severe events may
      play a role in the development of resilience to the impact of severe threatening
      events when these occur. METHOD: The Life Events and Difficulties Schedule (LEDS)
      (Brown & Harris, 1978) was used to record the life events experienced by 108
      depressed probands and their nearest aged siblings as well as 105 healthy control
      subjects and their nearest aged siblings. All subjects were interviewed using the
      Schedule for the Clinical Assessment of Neuropsychiatry (SCAN) (Wing et al.
      1990). RESULTS: Depressed probands were significantly more likely to have
      experienced a severe threatening event, loss event, or a humiliation event
      compared to the other subjects. These events also made up a greater proportion of
      the total number of events, in the depressed probands. Humiliation events were
      more frequent in depressed men than depressed women. There were no differences
      between the four groups for experiencing a non-severe event, although depressed
      probands also experienced more difficulties than the other three groups. Fifty
      six healthy subjects who had not become depressed despite having experienced at
      least one severe and threatening event, had significantly more non-severe events,
      than the 116 subjects who were depressed at the time of interview. CONCLUSIONS:
      The findings support the hypothesis that loss and humiliation events are
      particularly depressogenic. Experiencing a high rate of non-severe events may be
      associated with resilience to becoming depressed in the face of a threatening
      event.

PMID- 14580073
TI  - Life events, difficulties and dilemmas in the onset of chronic fatigue syndrome:
      a case-control study.
AB  - BACKGROUND: The role of stress in the onset of chronic fatigue syndrome is
      unclear. Our objectives in this study were first, to determine the relation
      between the onset of chronic fatigue syndrome and stressful life events and
      difficulties. Secondly, we examined the role of a particular type of problem,
      dilemmas, in the onset of chronic fatigue syndrome. METHOD: We used a case
      control design with 64 consecutive referrals from an Infectious Diseases/ Liaison
      Psychiatry Fatigue clinic and 64 age- and sex-matched controls from a general
      practice population control group in Leeds. We had two main outcome measures; the
      odds ratios of the risk of developing chronic fatigue syndrome after experiencing
      a severe life event, severe difficulties or both in the year and 3 months
      preceding onset; and the proportion of subjects in each group who experienced a
      dilemma prior to onset. RESULTS: Patients with chronic fatigue syndrome were more
      likely to experience severe events and difficulties in the 3 months (OR = 9, 95%
      CI 3.2 to 25.1) and year (OR = 4.3, 95% CI 1.8 to 10.2) prior to onset of their
      illness than population controls. In the 3 months prior to onset 19 of the 64
      patients (30%) experienced a dilemma compared to none of the controls.
      CONCLUSIONS: Chronic fatigue syndrome is associated with stressful events and
      difficulties prior to onset. Those events and difficulties characterized as being
      dilemmas seem to be particularly important.

PMID- 14580074
TI  - Personality and the experience of environmental adversity.
AB  - BACKGROUND: While psychiatric epidemiology often focuses on the causal
      relationship between environmental adversity and the individual (e.g. environment
      to person), individuals probably make important contributions to the quality of
      their environments (person to environment). METHOD: In a population based sample
      of > 7000 male and female adult twins, we examined the relationship between the
      personality trait of neuroticism (N) and the occurrence of stressful life events
      (SLEs) and the quality of interpersonal relationships (IPR). We compared the
      magnitude of the prediction of twin 1's self-reported SLEs and IPR from: (i) twin
      1's self-reported N; (ii) twin 2's report of twin 1's N; and (iii) twin 2's
      report of twin 2's N in monozygotic pairs. RESULTS: In our entire sample, self
      report N significantly predicted the occurrence of most SLEs and all dimensions
      of IPR. Using the co-twin's report of N produced associations that were of the
      same magnitude for SLEs and modestly weaker for IPR. In monozygotic pairs, the
      level of N in one twin predicted SLEs and IPR in the co-twin at levels similar to
      those found for the co-twin's report of N. Repeating these analyses with a
      prospective subsample produced similar results. CONCLUSION: An individual's
      personality in adulthood plays a significant role in influencing exposure to some
      forms of environmental adversity and this association is not the result of
      reporting bias. Furthermore, this relationship is largely mediated by a common
      set of familial factors that predispose both to a 'difficult' temperament and to
      environmental adversity. Developmental models of psychiatric illness should adopt
      an interactionist view of individuals and their environment (person and
      environment).

PMID- 14580075
TI  - Life events and early onset depression: cause or consequence?
AB  - BACKGROUND: Adverse life events prior to episodes of depression are assumed to
      play a causal role. Earlier studies have, however, not adequately controlled for
      the potential confounding effects of previous depression. METHOD: A two-phase
      study was nested within a six-wave population based cohort study of 1947
      adolescents. Interviews at two assessment phases with the CIS-R and CIDI were
      used to generate ICD-10 diagnoses of depressive disorder. Life events with longer
      term contextual threat were reported for the 6 months before first diagnosis and
      categorized on the basis of participant appraisal as negative and
      neutral/positive in effects. Previous depressive and anxiety symptoms were
      measured 6 months earlier. RESULTS: Pre-existing depressive and anxiety symptoms
      predicted later events, increasing three-fold the risks for both neutral/positive
      and negative events in females and increased seven-fold the risk of negative
      events in males. Life events in turn predicted the onset of depressive disorder
      independently of previous symptoms. Single negative events held an over five-fold
      elevated risk and multiple events an almost eight-fold higher risk. Personal
      threat and loss were associated with disorder in females but not males.
      CONCLUSIONS: The findings are consistent with a causal role for life events in
      early episodes of depression. The association also reflects a reciprocal
      relationship in which earlier symptoms predict later events, perhaps as a result
      of an individual's attempts to change unfavourable social circumstances.

PMID- 14580076
TI  - Primary anxiety disorders and the development of subsequent alcohol use
      disorders: a 4-year community study of adolescents and young adults.
AB  - BACKGROUND: Cross-sectional findings in community surveys of adults suggest that
      adolescent anxiety disorders are strong predictors of the subsequent onset of
      alcohol use, abuse and dependence. However, prospective data that follow a sample
      of adolescents into adulthood are needed to confirm these associations. METHOD:
      Baseline and 4-year follow-up data from the EDSP-Study, a prospective community
      survey of 3021 (2548 at follow-up) adolescents and young adults aged 14 to 24
      years at baseline carried out in Munich, were used. DSM-IV anxiety disorders,
      alcohol use and alcohol use disorders were assessed with the Munich-Composite
      International-Diagnostic-Interview (M-CIDI). Multiple logistic regression
      analysis, controlling for age, gender, other mental disorders, substance use
      disorders and antisocial behaviour was used to study the associations of baseline
      anxiety disorders with the subsequent onset and course of alcohol use and alcohol
      disorders. RESULTS: Baseline social phobia significantly predicts the onsets of
      regular use and hazardous use and the persistence of dependence. Panic attacks
      significantly predict the onsets of hazardous use and abuse as well as the
      persistence of combined abuse/dependence. Panic disorder significantly predicts
      the persistence of combined abuse/dependence. Other anxiety disorders do not
      significantly predict any of the outcomes. CONCLUSIONS: Panic and social phobia
      are predictors of subsequent alcohol problems among adolescents and young adults.
      Further studies are needed to investigate the underlying mechanisms and the
      potential value of targeted early treatment of primary panic and social phobia to
      prevent secondary alcohol use disorders.

PMID- 14580078
TI  - Spatial working memory ability is a marker of risk-for-psychosis.
AB  - BACKGROUND: Working memory has been identified as a core cognitive deficit in
      schizophrenia that is associated with negative symptoms, but it is unclear
      whether it is impaired prior to onset of psychosis in symptomatic patients.
      METHOD: Thirty-eight young people at ultra high-risk (UHR) of developing
      psychosis (of whom nine later became psychotic) were compared with 49 healthy
      controls on tests of spatial working memory (SWM) and delayed matching-to-sample
      (DMTS). RESULTS: Both SWM and DMTS performance was significantly poorer in the
      UHR groups. Those who later became psychotic generally performed more poorly than
      those who did not, although this did not reach significance for any measure. A
      significant association between SWM errors and negative symptoms was seen in the
      later-psychotic group only (P = 0.02). CONCLUSIONS: Spatial working memory
      abilities are impaired in those at high-risk for psychosis. The relationship
      between working memory and negative symptoms may be useful as a predictive tool.

PMID- 14580077
TI  - Older adults and withdrawal from benzodiazepine hypnotics in general practice:
      effects on cognitive function, sleep, mood and quality of life.
AB  - BACKGROUND: Older adults are the main recipients of repeat prescriptions for
      benzodiazepine (BZD) hypnotics. BZDs can impair cognitive function and may not
      aid sleep when taken continuously for years. This study therefore aimed to
      determine if withdrawing from BZDs leads to changes in patients' cognitive
      function, quality of life, mood and sleep. METHOD: One hundred and ninety-two
      long-term users of BZD hypnotics, aged > or = 65 years, were identified in 25
      general practices. One hundred and four who wished to withdraw were randomly
      allocated to one of two groups under double-blind, placebo controlled conditions:
      group A's BZD dose was tapered from week 1 of the trial; group B were given their
      usual dose for 12 weeks and then it was tapered. An additional group (C) of 35
      patients who did not wish to withdraw from BZDs participated as 'continuers'. All
      patients were assessed at 0, 12 and 24 weeks and 50% were reassessed at 52 weeks.
      RESULTS: Sixty per cent of patients had taken BZDs continuously for > 10 years;
      27% for > 20 years. Of all patients beginning the trial, 80% had successfully
      withdrawn 6 months later. There was little difference between groups A and B, but
      these groups differed from continuers (C) in that the performance of the
      withdrawers on several cognitive/psychomotor tasks showed relative improvements
      at 24 or 52 weeks. Withdrawers and continuers did not differ in sleep or BZD
      withdrawal symptoms. CONCLUSIONS: These results have clear implications for
      clinical practice. Withdrawal from BZDs produces some subtle cognitive advantages
      for older people, yet little in the way of withdrawal symptoms or emergent sleep
      difficulties. These findings also suggest that, taken long-term, BZDs do not aid
      sleep.

PMID- 14580079
TI  - Duration judgements in patients with schizophrenia.
AB  - BACKGROUND: The ability to encode time cues underlies many cognitive processes.
      In the light of schizophrenic patients' compromised cognitive abilities in a
      variety of domains, it is noteworthy that there are numerous reports of these
      patients displaying impaired timing abilities. However, the timing intervals that
      patients have been evaluated on in prior studies vary considerably in magnitude
      (e.g. 1 s, 1 min, 1 h etc.). METHOD: In order to obviate differences in abilities
      in chronometric counting and place minimal demands on cognitive processing, we
      chose tasks that involve making judgements about brief durations of time (< 1 s).
      RESULTS: On a temporal generalization task, patients were less accurate than
      controls at recognizing a standard duration. The performance of patients was also
      significantly different from controls on a temporal bisection task, in which
      participants categorized durations as short or long. Although time estimation may
      be closely intertwined with working memory, patients' working memory as measured
      by the digit span task did not correlate significantly with their performance on
      the duration judgement tasks. Moreover, lowered intelligence scores could not
      completely account for the findings. CONCLUSIONS: We take these results to
      suggest that patients with schizophrenia are less accurate at estimating brief
      time periods. These deficits may reflect dysfunction of biopsychological timing
      processes.

PMID- 14580080
TI  - Neuropsychological performance and dementia in depressed patients after 25-year
      follow-up: a controlled study.
AB  - BACKGROUND: Previous research has yielded conflicting evidence regarding the long
      term cognitive outcome of depression. Some studies have found evidence for a
      higher incidence of subsequent cognitive impairment or dementia, while others
      have refuted this. METHOD: Depression, neuropsychological performance, functional
      ability and clinical variables were assessed in a sample of patients who had been
      hospitalized for depression 25 years previously. RESULTS: Data were available on
      71 depressed patients (10 of whom were deceased) and 50 surgical controls. No
      significant differences were found between depressed subjects and controls on any
      neuropsychological measure. Ten depressed patients but no controls were found to
      have dementia at follow-up (continuity corrected chi2 = 5.93, P < 0.01). Presence
      of dementia was predicted by older age at baseline. Vascular dementia was the
      most common type. CONCLUSIONS: We conclude that this study did not find evidence
      that early onset depression is a risk factor for Alzheimer's disease, but that
      for a small subgroup there appears to be a link with vascular dementia. Several
      plausible explanations for this link, such as lifestyle factors, require further
      investigation.

PMID- 14580082
TI  - Psychiatric therapy in Georgian Britain.
AB  - BACKGROUND: This paper examines the emergence of 'oral treatment' in British
      psychiatry. METHOD: Re-examining a range of largely well-known sources, this
      article begins by outlining the social and intellectual shifts entailed by the
      secularization of madness at around 1660. The boundaries of various schools of
      psychiatric treatment are distinguished according to: (a) how much moral autonomy
      they accord the insane patient; and (b) whether they promote 'body' or 'mind'
      first (are 'somatopsychic' or 'psychosomatic'). I have also incorporated newly
      discovered material that proves the existence of 'classical moral treatment', or
      therapeutic argumentation. RESULTS: The paper outlines four distinct models of
      psychiatric treatment: 'classical moral treatment'; the 'pious fraud';
      'charismatic stewardship'; and 'moral treatment'. Neither the 'pious fraud' nor
      'charismatic stewardship' allowed that the patient was morally autonomous-
      rather, lunatics were stereotyped as animals. After the 1780s, some psychiatrists
      began practising in ways that understood the patient as being capable of some
      rationality. But none of these practitioners saw 'moral' therapies to be
      independent of the body's workings--they used: (a) psychological methods to ease
      the administration of physic; and/or (b) psychological and medical remedies
      interchangeably. The Tukes, who developed the famous asylum 'The Retreat' at
      York, were the first to find successful ways to make psychological means
      predominate in therapy. CONCLUSION: The Tukes of York are reinstalled in their
      position as founders of moral treatment as a therapy aimed at the autonomous
      human mind.

PMID- 14580081
TI  - Metabolic changes within the left dorsolateral prefrontal cortex occurring with
      electroconvulsive therapy in patients with treatment resistant unipolar
      depression.
AB  - BACKGROUND: The dorsolateral prefrontal cortex (DLPFC) is involved in the
      pathophysiology of major depression. In particular, metabolic (functional
      hypometabolism) and structural alterations have been described. In this study
      metabolic changes within the DLPFC of severely depressed patients before and
      after electroconvulsive therapy (ECT) were evaluated by proton STEAM spectroscopy
      (1H-MRS). METHOD: Twelve severely depressed patients with a diagnosis of major
      depressive episode, unipolar with melancholic features (DSM-IV), were enrolled,
      and the left dorsolateral prefrontal cortex (DLPFC) was investigated before and
      after unilateral ECT by 1H-MRS. Three of the four non-responding patients were
      remeasured a third time after a combined ECT/antidepressant pharmacotherapy. The
      results were compared with 12 age- and gender-matched controls. RESULTS: In
      depressed patients reduced glutamate/glutamine (Glx) levels were measured pre
      ECT; Glx concentrations correlated negatively with severity of depression. After
      successful treatment, Glx increased significantly and levels no longer differed
      from those of age-matched controls. CONCLUSIONS: Our results indicate that major
      depressive disorder is accompanied by state-dependent metabolic alterations,
      especially in glutamate/glutamine metabolism, which can be reversed by successful
      ECT.

PMID- 14580083
TI  - Patterns of co-morbidity in male suicide completers.
AB  - BACKGROUND: Psychiatric co-morbidity is thought to be an important problem in
      suicide, but it has been little investigated. This study aims to investigate
      patterns of co-morbidity in a group of male suicide completers. METHOD: One
      hundred and fifteen male suicide completers from the Greater Montreal Area and 82
      matched community controls were assessed using proxy-based diagnostic interviews.
      Patterns of co-morbidity were investigated using latent class analysis. RESULTS:
      Three subgroups of male suicide completers were identified (L2 = 171.62, df =
      2012, P < 0.05). they differed significantly in the amount of co-morbidity
      (Kruskal-Wallis chi2 = 71.227, df = 2. P < 0.000) and exhibited different
      diagnostic profiles. Co-morbidity was particularly found in subjects with
      disorders characterized by impulsive and impulsive-aggressive traits, whereas
      subjects without those traits had levels of co-morbidity which were not
      significantly different from those of controls (chi2 = 8.17, df = 4, P = 0.086).
      CONCLUSIONS: Suicide completers can be divided into at least three subgroups
      according to co-morbidity: a low co-morbidity group, a substance-dependent group
      and a group exhibiting childhood onset of psychopathology.

PMID- 14580084
TI  - The prevalence of DSM-IV personality pathology among individuals with bulimia
      nervosa, binge eating disorder and obesity.
AB  - BACKGROUND: There are numerous reports of personality disorder pathology in
      different eating disorders. However, few studies have directly compared
      personality pathology in bulimia nervosa, binge eating disorder and obesity. The
      present study examines group differences in DSM-IV personality pathology,
      considering the potential utility of understanding personality disorders in terms
      of diagnosis and dimensional scores. METHOD: Eating disorder diagnoses were
      established using the Eating Disorder Examination interview. Thirty-five bulimia
      nervosa patients, 15 binge eating disorder patients and 37 obese patients were
      assessed and compared on the International Personality Disorder Examination using
      categorical and dimensional personality disorder scores. RESULTS: For most
      personality disorders, there was a dichotomy of binge eaters versus non-binge
      eaters. In contrast, there was a continuum of severity in borderline personality
      disorder pathology between the groups. The dimensional system of measurement of
      personality pathology allowed for clearer differentiation between the groups.
      CONCLUSION: The study strongly indicates that personality disorder difficulties
      are present in patients who binge eat, while obese patients who do not binge eat
      display significantly less personality disorder pathology. Assessment of bulimia
      nervosa, binge eating disorder and obesity needs to address personality disorders
      and pathology. Dimensional markers of personality pathology can be used to
      supplement categorical diagnoses, providing information about the traits that
      underlie diagnosis.

PMID- 14580085
TI  - Family study of the aggregation of eating disorders and mood disorders.
AB  - BACKGROUND: Family studies have suggested that eating disorders and mood
      disorders may coaggregate in families. To study further this question, data from
      a family interview study of probands with and without major depressive disorder
      was examined. METHOD: A bivariate proband predictive logistic regression model
      was applied to data from a family interview study, conducted in Innsbruck,
      Austria, of probands with (N = 64) and without (N = 58) major depressive
      disorder, together with 330 of their first-degree relatives. RESULTS: The
      estimated odds ratio (OR) for the familial aggregation of eating disorders
      (anorexia nervosa, bulimia nervosa and binge-eating disorder) was 7.0 (95 % CI
      1.4, 28; P = 0.006); the OR for the familial aggregation of mood disorders (major
      depression and bipolar disorder) was 2.2 (0.92, 5.4; P = 0.076); and for the
      familial coaggregation of eating disorders with mood disorders the OR was 2.2
      (1.1, 4.6; P = 0.035). CONCLUSIONS: The familial coaggregation of eating
      disorders with mood disorders was significant and of the same magnitude as the
      aggregation of mood disorders alone--suggesting that eating disorders and mood
      disorders have common familial causal factors.

PMID- 14580087
TI  - Early gastrointestinal cancers.

PMID- 14580088
TI  - Early esophageal cancer: radiologic estimation of invasion into the muscularis
      mucosae.
AB  - BACKGROUND: Lymph node metastasis in squamous cell carcinoma of the esophagus is
      rare, and the cancer remains in the lamina propria mucosae. In cases with cancer
      invading the muscularis mucosae (MM), the incidence of lymph node metastasis is
      approximately 7%. For endoscopic treatment of mucosal cancer, it is necessary to
      diagnose cancer invasion into the MM. The aim of this study was to estimate
      cancer invasion into the MM by esophagography. METHODS: One hundred ten lesions
      of the slightly depressed type were classified into two groups: in group A,
      cancer was confined to the lamina propria mucosae; in group B, the cancer invaded
      the MM or slightly into the submucosa. Radiologic findings of each group were
      studied. RESULTS: In group A, 69% of 70 lesions showed mild depression and a
      smooth or undulated surface. Thickened folds were noticed in only 3%. In group B,
      83% of 40 lesions showed mild or moderate depression with well-defined granules.
      Thickened folds were evident in 78%. In the differentiation between groups, the
      accuracy rates of each finding of moderate depression, well-defined granules, and
      thickened folds were 85%, 73%, and 90%, respectively. The overall diagnostic
      accuracy rate was 90%. CONCLUSION: Esophagography is useful for estimation of
      cancer invasion into the MM and, hence, the decision to apply endoscopic
      treatment to mucosal cancer.

PMID- 14580089
TI  - What are the findings of esophageal cancer to be treated endoscopically?
AB  - In Japan, the results of histopathologic analyses on esophageal carcinomas have
      shown that almost all of them are squamous epithelial cancers. The abnormal
      epithelium that is difficult to differentiate by endoscopy can be easily
      visualized by chromoendoscopy with the use of iodine staining. Since the
      establishment of endoscopic mucosal resection (EMR), it has been used
      increasingly to treat mucosal cancers. It is necessary to diagnose accurately the
      depth of invasion of mucosal cancer when it is to be treated by EMR. In this
      article, we explain our routine techniques to visualize and interpret the lesions
      that are candidates for EMR. It is of great benefit to detect lesions at their
      early stage, which leads to the most desirable endoscopic treatment.

PMID- 14580090
TI  - Early esophageal carcinoma: endoscopic ultrasonography using the Sonoprobe.
AB  - BACKGROUND: Almost all cases of superficial esophageal carcinoma are curable by
      endoscopic mucosal resection (EMR), but a precise diagnosis of the depth of tumor
      invasion is necessary to assess the indication for EMR. Although endoscopy has a
      high rate of accuracy for diagnosing the depth of tumor invasion, it depends on
      the experience of the examiner in interpreting surface information of the
      lesions. Today, endoscopic ultrasonography (EUS) is one of the most powerful
      techniques for obtaining objective tomographic images of a tumor. The high
      frequency ultrasound probe is appropriate for EUS in cases of superficial
      esophageal carcinoma because of its excellent near-field resolution that provides
      precise ultrasound images under direct control of the endoscope. METHODS: We
      performed EUS with the Sonoprobe System in 85 cases of superficial esophageal
      carcinoma before treatment and evaluated the resected specimens
      histopathologically. We interpreted the depth of tumor invasion based on our
      fundamental studies of ultrasonograms taken with a 20-MHz probe. RESULTS: The
      clinical usefulness of the Sonoprobe with linear and radial scanning modes is due
      to its capacity to differentiate between mucosal and submucosal carcinoma by
      means of analyses of the muscularis mucosae. Although a clear assessment of
      microinvasion and lymphoid hyperplasia surrounding the tumor of interest remains
      speculative, the diagnostic accuracy rate for 96 lesions of superficial
      esophageal carcinoma reached 93% in terms of differentiating between mucosal from
      submucosal carcinoma. CONCLUSION: EUS with the Sonoprobe can play an important
      role in the pretreatment diagnosis of superficial esophageal carcinomas.

PMID- 14580091
TI  - Early gastric carcinomas in the cardiac region: diagnosis with double-contrast x
      ray studies.
AB  - BACKGROUND: The ratio of early to advanced gastric carcinomas in the cardiac
      region is significantly low. It is necessary to establish methods of early
      diagnosis of gastric carcinomas in the cardiac region. METHODS: Twenty cases (21
      lesions) of early gastric carcinomas in the cardiac region were resected between
      1997 and 2001. We studied the macroscopic characteristics of the specimens, films
      of double-contrast upper gastrointestinal studies before operations, and the
      detectabilities of findings in each projection. RESULTS: Four of 21 early gastric
      carcinomas in the cardiac region were on the anterior wall, 10 were on the lesser
      curvature, and seven were on the posterior wall. In seven of 21 lesions the
      carcinomas were not detected in the resected specimens macroscopically; in five,
      the area of carcinoma was not clearly traced in the resected specimens; and in
      nine, the area of carcinomas was clearly traced. In the morphologic study, 16
      (76.2%), two (9.5%), two (9.5%), and one (4.8%) of the 21 lesions showed the
      superficial depressed type (IIc), superficial elevated type (IIa), superficial
      elevated and superficial depressed type (IIa + IIc), flat and superficial
      depressed type (IIb + IIc), respectively. Mucosal reddening was seen in 11, and
      mucosal discoloration was seen in one; change of color was not seen in the
      remaining nine lesions. Twenty lesions were diagnosed as differentiated
      adenocarcinomas, and one lesion was diagnosed as undifferentiated adenocarcinoma.
      Radiologically, early gastric carcinomas in the cardiac region had the following
      features: localized shallow barium deposits, localized abnormal barium coating,
      and niche and radiolucent lesions. Four (100%) of four lesions on the anterior
      wall, 10 (100%) of 10 lesions on the lesser curvature, and seven (100%) of seven
      lesions on the posterior wall were detected in the half-standing, prone, right
      anterior, oblique projection. Seven (100%) of seven lesions on the posterior wall
      and 10 (100%) of 10 lesions on the lesser curvature were detected in the half
      standing, supine, left anterior, oblique projection. CONCLUSION: Even though most
      early gastric carcinomas in the cardiac region demonstrate few macroscopic
      findings, the half-standing, prone, right anterior, oblique projection and the
      half-standing, supine, left anterior, oblique projection are useful in the double
      contrast studies.

PMID- 14580093
TI  - Evaluation of bowel and mesenteric injury: role of multidetector CT.
AB  - The development of thin-section multidetector computed tomography has improved
      the accuracy of computed tomography in the evaluation of abdominal trauma.
      Multidetector computed tomography is more sensitive and specific than diagnostic
      peritoneal lavages, abdominal sonography, and clinical examination for the
      detection of bowel and mesenteric injury. Computed tomographic findings include
      pneumoperitoneum, visualization of direct tears in the bowel wall,
      intraperitoneal fluid, bowel wall thickening, abnormal bowel wall enhancement,
      and mesenteric infiltration or hematoma.

PMID- 14580092
TI  - Early invasive colorectal carcinomas with submucosal invasion: radiographic
      characteristics with barium double contrast images.
AB  - BACKGROUND: We assessed the radiographic characteristics of early colorectal
      carcinomas with submucosal invasion (CCSI) with the use of double-contrast
      images. METHODS: From 1989 to 1997, 193 patients with 196 CCSI lesions underwent
      double-contrast barium enema examinations. Three gastrointestinal radiologists
      retrospectively reviewed the radiographic characteristics of the lesions and
      classified them as protruding and depressed types by consensus. Further,
      subclassifying the protruding into lobular and smooth types was accomplished on
      the basis of surface structure. Each type was compared with pathologic findings
      of resected specimens. RESULTS: The incidence of the protruding type was 98.0%,
      and that of the depressed type was only 2.0%. The proportion of smooth lesions
      was 49.0% for the protruding type; these had a mean diameter of 17.9 mm, which
      was significantly smaller than the 23.1 mm mean observed for lobular lesions (p <
      0.01). Of the smooth lesions, 44.7% demonstrated massive invasion, whereas 91.8%
      of lobular lesions exhibited only slight or moderate invasion into the submucosa
      (p < 0.01). The extent of invasion of the smooth lesions was greater than that
      for their lobular counterparts in terms of venous and lymph node involvement.
      CONCLUSION: Almost all CCSIs could be identified radiologically as protruding
      lesions; these had a smooth rather than a lobulated surface and demonstrated
      greater malignancy, despite the smaller size. It is clinically important to
      discriminate these from other polypoid lesions in establishing patient treatment.
      Double-contrast imaging is useful for evaluation of the surface characteristics
      of CCSIs in barium enema studies.

PMID- 14580094
TI  - Small intestinal angiolipoma: MR imaging appearance.
AB  - We report the magnetic resonance imaging finding in a case of small intestinal
      angiolipoma. Small bowel enteroclysis showed a well-defined, lobulated polypoid
      lesion in the proximal ileum. The mass showed central high signal intensity with
      peripheral iso-signal intensity on T1-weighted in-phase images. The central high
      signal intensity changed to low signal intensity on T1-weighted out-of-phase
      images. After contrast injection, the mass had a strong enhancement along the
      periphery of the lesion on fat-saturated T1-weighted images. Characteristic
      decreased signal intensity on out-of-phase T1-weighted images and strong
      enhancement on postcontrast images of the small bowel mass suggest the diagnosis
      of angiolipoma.

PMID- 14580095
TI  - Use of the Bard Memotherm self-expanding metal stent in the palliation of colonic
      obstruction.
AB  - BACKGROUND: Self-expanding metal stents (SEMS) are a recognized means of
      palliating large bowel obstruction due to colonic neoplasia. The literature
      mainly relates to the use of modified esophageal stents (expanded diameter, 18-22
      mm) in the colorectum. Stent migration has been a common complication and may be
      related to expanded stent diameter. This series reports our experience with the
      Memotherm Colorectal SEMS (expanded diameter, 25-30 mm). METHODS: Prospective
      data were collected from February 1999 to September 2000. Sixteen patients (age
      range = 61-99 years) were considered for the Memotherm Colorectal SEMS. Stents
      were inserted radiologically under fluoroscopic control. Outcome was classified
      as a technical success (stent in correct position and expanded) and a clinical
      success (colon decompressed, symptoms relieved, and bowels working). RESULTS:
      Thirteen cases (81%) underwent successful SEMS placement. These were technically
      and clinically successful. Two cases required insertion of two overlapping stents
      to traverse long strictures. Three unsuccessful cases were emergency
      presentations in which a guidewire could not be passed across the lesion. Two of
      these were due to benign strictures and the third to extrinsic compression by
      ovarian carcinoma. CONCLUSION: In our experience, the Memotherm Colorectal SEMS
      was easy to use, was effective in the palliation of obstructing colorectal
      carcinoma, and appeared to reduce the risk of stent migration.

PMID- 14580096
TI  - Detection and characterization of focal liver lesions using superparamagnetic
      iron oxide-enhanced magnetic resonance imaging: comparison between ferumoxides
      enhanced T1-weighted imaging and delayed-phase gadolinium-enhanced T1-weighted
      imaging.
AB  - BACKGROUND: Double contrast magnetic resonance (MR) imaging using
      superparamagnetic iron oxide (SPIO) and gadolinium (Gd) is performed to detect
      and characterize focal liver lesions. However, this technique is a costly and
      lengthy process. The purpose of this study was to determine the usefulness of
      SPIO-enhanced MR imaging including SPIO-enhanced T1-weighted imaging in
      diagnosing focal liver lesions. METHODS: Eighty-four focal liver lesions were
      examined with a 1.5-T MR unit. Transverse precontrast T1- and T2-weighted images
      and SPIO (ferumoxides)-enhanced T1- and T2-weighted images were obtained,
      followed by Gd-enhanced T1 -weighted imaging. The Gd set (i.e., precontrast T1-
      and T2-weighted and delayed-phase gadolinium-enhanced T1-weighted images) and
      ferumoxides set (i.e., precontrast T1- and ferumoxides-enhanced T1- and T2
      weighted images) were reviewed by two independent readers. RESULTS: More lesions
      were detected from the ferumoxides set than from the Gd set. Ferumoxides-enhanced
      T1-weighted imaging showed enhancement patterns of the lesions similar to those
      of delayed-phase Gd-enhanced T1-weighted imaging. The diagnoses of hepatic
      metastasis and cyst by the ferumoxides set were similar to those by the Gd set.
      However, a dynamic study may be inevitable for the diagnosis of hepatocellular
      carcinoma and hemangioma. CONCLUSION: The ferumoxides set was useful for the
      detection of focal hepatic lesions. Ferumoxides-enhanced T1-weighted imaging may
      replace delayed-phase gadolinium-enhanced T1-weighted imaging in the diagnosis of
      hepatic metastasis and cysts.

PMID- 14580097
TI  - Common bile duct diameters after endoscopic sphincterotomy in patients with
      common bile duct stones: ultrasonographic evaluation.
AB  - BACKGROUND: One of the most reliable, frequently used imaging techniques in
      cholestasis is ultrasonography (US) for the diagnosis of common bile duct (CBD)
      stones. METHODS: In this study, changes in diameters of CBD were determined
      ultrasonographically before and after endoscopic sphincterotomy (ES) in 46
      patients with stone-induced dilated CBD. RESULTS: There was a significant
      decrease in CBD diameter measured 1 week after ES and extraction of stone (p <
      0.001). In 87% of cases, the difference was more significantly pronounced during
      the first 24 h of ES. The mean CBD diameters on US were 13.70 +/- 3.00 mm (10-21
      mm) before and 9.13 +/- 2.90 mm (4.2-18 mm) 24 h after endoscopic treatment (p <
      0.001). After ES, six patients (13%) with inadequate decreases in CBD diameters
      were found to have residual stones. CONCLUSION: US can show residual stones in
      the CBD with the same efficacy as endoscopic retrograde cholangiopancreatography.

PMID- 14580098
TI  - Virtual CT cholangiography in patients with choledocholithiasis.
AB  - BACKGROUND: We evaluated the feasibility and accuracy of virtual computed
      tomographic cholangiography (VCTC) in detecting choledocholithiasis and imaging
      anatomic variations of the biliary tree. METHODS: Thirty-three consecutive
      patients with clinical and biological signs of choledocholithiasis underwent
      spiral CT after intravenous infusion of iotroxindimeglumine. Patients with total
      serum bilirubin levels above 3 mg/dL were not included in this study. Spiral data
      sets were used to construct intralumenal images of the biliary tree. The images
      were reviewed by two abdominal radiologists. The biliary ducts were divided into
      three segments, so the analysis was based on 99 segments. The diagnosis obtained
      by VCTC was compared with the final diagnosis established by endoscopic
      retrograde cholangiography or intraoperative cholangiography. RESULTS: VCTC
      correctly depicted biliary stones in nine of 10 patients and anatomic variations
      in all five patients, and no false-positive cases were observed. VCTC showed
      excellent endolumenal visualization of 87 of 99 segments of the biliary tree. The
      processing time (9.3 +/- 2.1 min) was particularly short. CONCLUSION: VCTC with
      intravenous infusion of iotroxindimeglumine may be a feasible clinical tool, with
      acceptable accuracy in selected cases.

PMID- 14580099
TI  - Endolumenal ultrasonography in the diagnosis of pancreatic diseases.
AB  - We evaluated the usefulness and limitations of endoscopic ultrasonography (EUS)
      in pancreatic mass lesions. EUS was useful in detecting small pancreatic mass
      lesions, especially ductal adenocarcinomas smaller than 20 mm and small islet
      cell tumors smaller than 10 mm. In some of these cases, characteristic echo
      patterns were specific and useful for differential diagnosis from focal
      pancreatitis. However, when EUS did not clearly delineate a tumor at the stenotic
      area of the main pancreatic duct, transpapillary pancreatoscopy and
      biopsy/cytology were sometimes effective to obtain a definitive diagnosis. EUS
      fine-needle aspiration should be performed in conjunction with imaging modalities
      when the differential diagnosis of a pancreatic mass is difficult to make.
      Although the value of EUS in cancer staging was overestimated, EUS in conjunction
      with spiral computed tomography or magnetic resonance imaging should be performed
      for such a purpose. Usefulness and limitations of intraductal ultrasonography
      (IDUS) also were evaluated. IDUS was useful in detecting carcinoma in situ and
      small tumors and in assessing parenchymal invasion and the intraductal spread of
      the tumor. IDUS was also useful in accurately localizing islet cell tumor and in
      differentiating benign from malignant cases of localized stenosis of the main
      pancreatic duct. Thus, EUS and IDUS are indispensable modalities in the diagnosis
      of pancreatic diseases.

PMID- 14580100
TI  - Preoperative assessment of pancreatic malignancy using endoscopic ultrasound.
AB  - BACKGROUND: Endoscopic ultrasound (EUS) has been regarded as the most accurate
      modality for locoregional staging of pancreatic malignancy. However, several
      recent studies have questioned this. The current study assessed the accuracy of
      EUS in determining preoperative resectability of pancreatic neoplasia. METHODS: A
      retrospective review was performed of patients with pancreatic malignancy who had
      preoperative EUS and underwent surgery. EUS-predicted resectability was compared
      with surgical resectability. Where available, accuracies of vascular and nodal
      staging were also assessed. RESULTS: Forty-five patients were identified (mean
      age 60 years, age range = 36-79 years). All patients underwent surgical
      exploration; vascular staging was available in 32 cases and 17 cases underwent
      surgical resection. The sensitivity, specificity, and accuracy of EUS in
      determining unresectability were 66%, 100%, and 78% respectively. Overall EUS
      stage concurred with surgical stage in 56%, greater than surgical stage in 4%,
      and less than surgical stage in 40%. Vascular staging on EUS had a sensitivity of
      69% and a specificity of 100%. Accuracy of nodal staging was 71%. CONCLUSION: EUS
      had a high specificity for assessing unresectable pancreatic malignancy. This
      technique should be used to avoid unnecessary surgical exploration of incurable
      lesions. However, EUS had only a moderate sensitivity, and a proportion of
      patients staged preoperatively as having resectable disease will not be
      surgically resectable.

PMID- 14580101
TI  - Evaluation of the permeability of pancreaticogastric anastomoses (PGA) with
      dynamic magnetic resonance pancreatography after secretin stimulation (secretin
      MRCP).
AB  - BACKGROUND: Because some investigators have reported the systematic occurrence of
      exocrine pancreatic insufficiency after pancreaticoduodenectomy with
      pancreaticogastric anastomosis (PGA), we assessed PGA patency after
      pancreaticoduodenectomy. METHODS: Nineteen patients underwent
      pancreaticoduodenectomy, and their PGAs were studied prospectively with secretin
      magnetic resonance cholangiopancreatography (MRCP). After administration of
      negative bowel contrast agent, single-shot fast spin-echo T2-weighted dynamic MR
      pancreatograms were obtained before and every minute for 12 min after secretin
      injection. Morphologic features of the pancreatic parenchymal and pancreatic duct
      were monitored (diameter and winding aspect of the pancreatic duct, pancreatic
      thickness, direct visualization of the anastomotic site). PGA permeability was
      classified into four grades, from 0 (obstruction) to 3 (good permeability).
      Pancreatic function was assessed by fecal-1 elastase concentration, fasting blood
      glucose, and fasting serum insulin level. RESULTS: MRCP grades were 0 in two
      patients, 1 in four, 2 in five, and 3 in eight. The anastomotic site was
      visualized in 10 patients. Pancreatic parenchymal atrophy was discovered in four
      patients. There were statistically significant relations between secretin MRCP
      permeability grade and fecal-1 elastase concentration (p < 0.03) and between
      secretin MRCP permeability grade and pancreatic atrophy (p < 0.005). In contrast,
      fecal-1 elastase concentration was lower than the normal value in all but one
      case. There was no statistically significant relation between fecal-1 elastase
      concentration and other morphologic data. CONCLUSION: Secretin MRCP may indicate
      PGA stenosis or dysfunction, but it is not the only factor suggesting exocrine
      pancreatic insufficiency. Thus the major role of PGA may be the preservation of
      long-term endocrine function.

PMID- 14580102
TI  - Celiac plexus block: evaluation of injectate spread by three-dimensional computed
      tomography.
AB  - We describe a case of pancreatic cancer in which the spread pattern of injectate
      during neurolytic celiac plexus block was evaluated by three-dimensional helical
      computed tomography. Three-dimensional images provide excellent visualization of
      the spread patterns of injectate in a target site, which appears to provide
      patients with effective relief from intractable pain.

PMID- 14580103
TI  - Ultrasound in abdominal tuberculosis.
AB  - BACKGROUND: The present study was done to emphasize the importance of ultrasound
      (US) and US-guided fine-needle aspiration biopsy (FNAB) in the diagnosis of
      abdominal tuberculosis. METHODS: Sixty-six proven cases of abdominal tuberculosis
      were selected for this study. The diagnosis was based on clinical features, US
      observations, FNAB, operative findings, and responses to appropriate
      antitubercular treatment. The US findings were interpreted with regard to the
      involvement of lymph nodes, intestine, peritoneum, solid viscera, and abdominal
      abscesses. Patients with disease limited to the musculoskeletal and genitourinary
      systems were not included in the study. RESULTS: Peritoneal tuberculosis was the
      most common form, of the "wet" ascitic type. Ascites was clear in 19 patients and
      complex in 17. Tuberculous lymphadenopathy was seen in 37 patients. There was a
      predilection of periportal, peripancreatic, and mesenteric locations compared
      with the degree of retroperitoneal involvement. Calcification and heterogeneous
      echotexture were seen in seven cases. FNAB confirmed the diagnosis of tubercular
      lymphadenopathy in 19 patients. Intestinal disease was seen in 14 patients.
      Hepatic or splenic involvement was seen as diffuse organomegaly; less commonly,
      focal lesions were seen. CONCLUSION: This combination of US findings in proper
      clinical settings are diagnostic of tuberculosis. FNAB confirms the diagnosis in
      lymphadenopathy, abscesses, and focal lesions of the viscera.

PMID- 14580104
TI  - CT virtual intravascular endoscopy of abdominal aortic aneurysms treated with
      suprarenal endovascular stent grafting.
AB  - BACKGROUND: We investigated the clinical applications of virtual intravascular
      endoscopy (VIE) in patients with abdominal aortic aneurysms (AAA) treated by
      endovascular stent grafting with a suprarenal component. METHODS: Thirty-four
      patients with AAA undergoing endovascular stent grafting were included in the
      study (28 male, six female; mean age = 76 years). Helical computed tomography
      (CT) scanning was performed within 1 week after stent graft implantation. All
      patients received a Zenith/AAA endovascular graft with uncovered suprarenal
      struts 2.5 cm long placed around the level of the renal arteries. VIE images were
      created for each patient. The follow-up periods ranged from 3 to 18 months (mean
      = 8.3 +/- 3.7 months). RESULTS: Three of 34 celiac arteries, 22 of 34 superior
      mesenteric arteries, 32 of 34 right renal arteries, and 30 of 35 left renal
      arteries were affected by the suprarenal stent struts (wires) to different
      extents. VIE was able to demonstrate the struts, arterial ostia, and the
      strut/ostia configuration. Follow-up CT showed that all of these aortic branches
      were patent. CONCLUSION: Our preliminary experience has demonstrated that VIE is
      a novel imaging technique to visualize the three-dimensional intralumenal
      relationship of the aortic stent struts to the arterial ostia in patients with
      AAA after suprarenal stent graft placement.

PMID- 14580105
TI  - Localized cystic disease of the kidney: CT findings.
AB  - BACKGROUND: We assessed the clinical and computed tomographic (CT) features of
      localized cystic disease of the kidney and how these features differentiate this
      disease from other renal cystic diseases. METHODS: Medical records and CT scans
      of seven patients with localized cystic disease were reviewed retrospectively.
      Pathologic confirmation in five patients was done by surgery. The subjects
      consisted of four males and three females, with an age range of 29-74 years.
      RESULTS: Localized cystic disease in five patients was an incidental finding.
      Clinical presentations in the other two patients included dark urine color,
      palpable flank mass, and generalized weakness. There was no patient with
      impairment of renal function associated with renal cystic disease. Six patients
      had cystic renal lesions in the left kidneys, and one patient had lesions in the
      right kidney. Six patients had cysts in a localized area in the affected kidney,
      and the remaining patient had diffuse involvement of the entire kidney. The upper
      pole was most frequently involved. CT appearance was characterized by multiple,
      variable size cysts conglomerated to islets of cysts that were separated by the
      normal renal parenchymal band. CONCLUSION: Localized cystic disease of the kidney
      has characteristic CT findings that distinguish it from other renal cystic
      diseases, making follow-up without surgical intervention possible.

PMID- 14580106
TI  - The effect of fluconazole treatment on tumor necrosis factor-alpha production in
      murine candidiasis.
AB  - That systemic candidiasis increases TNF-alpha has been proved in various studies.
      In our study, we investigated if fluconazole too, which is used in treatment, has
      an additional effect on the increase of TNF-alpha. On the sixth day of the
      experimental infection, it was measured that TNF-alpha levels of candidiasis was
      699 +/- 60 pg/ml whereas it was 683 +/- 35 pg/ml in the mice that were treated
      with fluconazole. TNF-alpha levels were measured by enzyme-linked immunosorbant
      assay. Due to the fact that no statistically significant difference was found
      between them (p > .05) it was thought that fluconazole did not have an additional
      effect on the increase of TNF-alpha in candidiasis.

PMID- 14580107
TI  - Nonlinear systems in medicine.
AB  - Many achievements in medicine have come from applying linear theory to problems.
      Most current methods of data analysis use linear models, which are based on
      proportionality between two variables and/or relationships described by linear
      differential equations. However, nonlinear behavior commonly occurs within human
      systems due to their complex dynamic nature; this cannot be described adequately
      by linear models. Nonlinear thinking has grown among physiologists and physicians
      over the past century, and non-linear system theories are beginning to be applied
      to assist in interpreting, explaining, and predicting biological phenomena. Chaos
      theory describes elements manifesting behavior that is extremely sensitive to
      initial conditions, does not repeat itself and yet is deterministic. Complexity
      theory goes one step beyond chaos and is attempting to explain complex behavior
      that emerges within dynamic nonlinear systems. Nonlinear modeling still has not
      been able to explain all of the complexity present in human systems, and further
      models still need to be refined and developed. However, nonlinear modeling is
      helping to explain some system behaviors that linear systems cannot and thus will
      augment our understanding of the nature of complex dynamic systems within the
      human body in health and in disease states.

PMID- 14580110
TI  - An account of the experiment of transfusion, practiced upon a man in London.
      1667.

PMID- 14580111
TI  - A conversation with John Sulston.
AB  - Sir John Sulston was a co-winner of the Nobel Prize for Medicine in 2002. He won
      the prize for his discoveries concerning "genetic regulation of organ development
      and programmed cell death," along with his colleagues sydney Brenner and H.
      Robert Horvitz. Dr. Sulston was founding director of the Sanger Centre,
      Cambridge, England, which he headed from 1992 to 2000. From 1993 to 2000, he led
      the British arm of the international team selected to work on the Human Genome
      Project. He is co-author of the book The Common Thread: A Story of Science,
      Politics, Ethics, and the Human Genome, published by Joseph Henry Press in
      2002.This interview was conducted on December 20, 2002, shortly after Dr. Sulston
      was awarded his Nobel Prize and was originally broadcast on that date on radio
      station WPKN-FM in Bridgeport, Connecticut. The interview was conducted by
      Valerie Richardson, the Managing Editor of The Yale Journal of Biology and
      Medicine.Dr. Sulston has been an outspoken advocate against letting the data from
      the Human Genome Project become property of commercial interests that would
      charge the world's scientific community for its use. Since leaving the Sanger
      Institute, he has worked with OxFam, the Oxford Campaign for Famine Relief.

PMID- 14580109
TI  - Staphylococcus aureus cholecystitis: a report of three cases with review of the
      literature.
AB  - Infection of the hepatobiliary system is most commonly due to enteric bacteria.
      We report three unusual cases of acute cholecystitis in which Staphylococcus
      aureus was the primary pathogen. Infection of the gallbladder with this organism
      has been rarely described and may be associated with gallstones and obstructive
      disease as well as acalculous cholecystitis in the setting of staphylococcal
      bacteremia and endocarditis. Two of our patients had multiple chronic medical
      conditions and were infected with oxacillin-resistant S. aureus (ORSA) suggesting
      nosocomial acquisition. Including our cases with a review of the literature,
      three of nine reports of S. aureus cholecystitis were associated with infectious
      endocarditis. Thus, the finding of S. aureus cholecystitis with bacteremia is
      rare and should prompt an investigation for a possible endovascular focus of
      infection.

PMID- 14580112
TI  - Pediatric grand rounds: a tribute to Norman J. Siegel, M.D.
AB  - At ceremonies held in Baltimore Maryland on May, 4, 2002, Dr. Howard A Pearson,
      Professor of Pediatrics, was awarded the John A. Howland award of the American
      Pediatric Society, probably the most prestigious award of American Pediatrics.
      Dr. Pearson had been nominated for the award by Dr. Norman Siegel. The Department
      of Pediatrics Grand Rounds on Wednesday noon, October 26, 2002 was originally
      scheduled as a repetition of the presentation by Dr. Siegel and the acceptance by
      Dr. Pearson for those who could not be in Baltimore. However; in a number of
      meetings, unknown to Dr. Siegel, it was unanimously decided that it would be very
      appropriate to instead honor him as he stepped down from his position as Vice-
      and Interim Chairman of Pediatrics, and to formally thank him for his long and
      faithful service to the Department of Pediatrics, the Yale University School of
      Medicine, and the Yale New Haven Hospital.

PMID- 14580108
TI  - Neurotransmission and the synaptic vesicle cycle.

PMID- 14580113
TI  - What is life? Prerequisites for a definition.
AB  - Biologists view life as transient while theologians see it as eternal. An
      unbiased definition for life would respect both views until one or both were
      eliminated by evidence. This paper identifies pre-requisites for such a
      definition. First among these is that all assumptions be made explicit. Currently
      "life" is surrounded by implicit assumptions, e.g., that it is what organisms
      lose at death or that it is eternal, that its quality is inversely related to
      personal distress, that it originated some four billion years ago, and that
      animate matter can be distinguished from inanimate matter. None of these
      assumptions are supported by data. It is possible therefore that "life" is as
      meaningless as phlogiston. If life has meaning, i.e., if it is true, it must be
      as permanent as buoyancy, gravity, electricity, and the other truths of nature.
      Any definition for life that would permit such truth to be seen must be free of
      unwarranted assumptions. For the moment, at least, such a definition would need
      to be loosely structured and broadly focused. It would need to describe the long
      and convoluted process by which matter and energy form organisms which then
      evolve to form conscious organisms which then explore nature and eventually
      discover truth. Such a definition would include all the reactions and
      interactions of matter and energy and all the aspects of conscious discovery. It
      would suffer from superficiality, but, by being free from bias, provide a
      foundation for dialogue between biologists and theologians.

PMID- 14580114
TI  - The 2003 anatomy ceremony: a service of gratitude.
AB  - In keeping with a long-standing tradition, Yale Medical and Physician Associate
      students gather at a ceremony each year after the completion of the anatomy
      course. The ceremony is a chance to reflect and to give thanks. It gives students
      the opportunity to articulate their gratitude to the selfless individuals who
      donated their bodies for the benefit of education. Many family members of the
      donors attend the ceremony. By reading poetry, performing musical pieces, and
      presenting works of art, the students and their teachers express some of the
      emotions and thoughts that the anatomy course has evoked. The following are some
      of the contributions presented at this year's ceremony.

PMID- 14580115
TI  - Why do seizures cause loss of consciousness?
AB  - Model systems are needed for the scientific investigation of consciousness. A
      good model system should include variable states of consciousness, allowing the
      relationship between brain activity and consciousness to be investigated.
      Examples include sleep, anesthesia, focal brain lesions, development, evolution,
      and epilepsy. One advantage of epilepsy is that changes are dynamic and rapidly
      reversible. The authors review previous investigations of impaired consciousness
      in epilepsy and describe new findings that may shed light on both normal and
      abnormal mechanisms of consciousness. Abnormal increased activity in fronto
      parietal association cortex and related subcortical structures is associated with
      loss of consciousness in generalized seizures. Abnormal decreased activity in
      these same networks may cause loss of consciousness in complex partial seizures.
      Thus, abnormally increased or decreased activity in the same networks can cause
      loss of consciousness. Information flow during normal conscious processing may
      require a dynamic balance between these two extremes of excitation and
      inhibition.

PMID- 14580116
TI  - Gradients of neurotrophins, ion channels, and tuning in the cochlea.
AB  - The mammalian cochlea is exquisitely designed to decompose complex sounds into
      their component frequencies, accounting in part for the superb auditory
      discrimination displayed by many species. To perform this task, numerous
      mechanical and electrical specializations are graded along the length of the
      cochlea that create a tonotopic map in which sounds of different frequencies
      produce maximal responses at different cochlear locations. Graded mechanical
      features include structural changes in the vibratory basilar membrane, on which
      the hair cell sensory receptors sit, to systematic changes in receptor cell size
      and stereociliary length. Furthermore, there is growing evidence that frequency
      specificity does not stop at mechanical and morphological elements in the
      cochlea, but also extends to the intrinsic electrical profile of the hair cell
      sensory receptors and the first neural element in the auditory system--the spiral
      ganglion neurons.

PMID- 14580118
TI  - Twitches versus movements: a story of motor cortex.
AB  - Modern study of the neurophysiology of the cerebral cortex began with Fritsch and
      Hitzig's discovery that electrical stimulation of the cortex produces movements.
      The importance of this discovery was threefold: it was the first demonstration of
      cortex devoted to motor function, the first indication that the cortex was
      electrically excitable, and the first evidence of a topographically organized
      representation in the brain. Fritsch and Hitzig's basic findings were soon
      replicated by Ferrier, but there were differences between the two studies in both
      method and interpretation. These different approaches have continued to
      reverberate in research on the function of motor cortex from the late 19th
      century to the present day.

PMID- 14580119
TI  - Axon guidance by growth cones and branches: common cytoskeletal and signaling
      mechanisms.
AB  - Growing axons are guided to appropriate targets by responses of their motile
      growth cones to environmental cues. Interstitial axon branching is also an
      important form of axon guidance in the mammalian CNS. Visualization of growing
      axons in cortical slices and in dissociated cortical cultures showed that growth
      cone pausing behaviors demarcate sites of future axon branching. Studies of
      vertebrate and invertebrate growth cones suggest common mechanisms that regulate
      growth cone behaviors and axon branching. These include reorganization of the
      actin and microtubule cytoskeleton, dynamic interactions between microtubules and
      actin filaments, effects of axon guidance molecules, actions of actin regulatory
      proteins, and dynamic changes in intracellular calcium signaling. Future
      challenges will be to extend high-resolution imaging of single neurons to studies
      of intracellular events in the intact nervous system and to apply knowledge of
      developmental mechanisms to the promotion of axon sprouting after injury in the
      adult CNS.

PMID- 14580120
TI  - Functional imaging and pain: behavior, perception, and modulation.
AB  - Time-dependent increases of local metabolic or blood flow rates have been
      described in spinal cord and brain during acute and chronic pain states in
      experimental animals, in parallel with changes of different behavioral endpoints
      of pain and hyperalgesia. In healthy human volunteers, pain intensity-related
      hemodynamic changes have been identified in a widespread, bilateral brain system
      including parietal, insular, cingulate, and frontal cortical areas, as well as
      thalamus, amygdala, and midbrain. Specific patterns of activity may characterize
      hyperalgesic states and some chronic pain conditions. Forebrain nociceptive
      systems are under inhibitory control by endogenous opioids and can be affected by
      acute administration of mu-opioid receptor agonists. Anticipation of pain may in
      itself induce changes in brain nociceptive networks. Moreover, pain-related
      cortical activity can be modulated by hypnotic suggestions, focusing or diverting
      attention, and placebo. These findings begin to disclose the spatio-temporal
      dynamics of brain networks underlying pain perception and modulation.

PMID- 14580121
TI  - P2X receptor-mediated modulation of sensory transmission to the spinal cord
      dorsal horn.
AB  - In the somatosensory system, P2X receptors are expressed on both peripheral and
      central terminals of primary afferent neurons. Those expressed on peripheral
      terminals are activated in response to both nociceptive and innocuous stimuli,
      whereas those at central terminals ("central terminal P2X receptors") play an
      important role in modulating sensory transmission to the spinal cord dorsal horn.
      The author reviews recent studies on the central terminal P2X receptors. It is
      proposed that central terminal P2X receptors, once activated, may be involved in
      both central sensitization and initiation of pain. Thus, these receptors may
      represent a promising target for therapeutic management of pathological pain.

PMID- 14580117
TI  - Complex receptive fields in primary visual cortex.
AB  - In the early 1960s, Hubel and Wiesel reported the first physiological description
      of cells in cat primary visual cortex. They distinguished two main cell types:
      simple cells and complex cells. Based on their distinct response properties, they
      suggested that the two cell types could represent two consecutive stages in
      receptive-field construction. Since the 1960s, new experimental and computational
      evidence provided serious alternatives to this hierarchical model. Parallel
      models put forward the idea that both simple and complex receptive fields could
      be built in parallel by direct geniculate inputs. Recurrent models suggested that
      simple cells and complex cells may not be different cell types after all. To this
      day, a consensus among hierarchical, parallel, and recurrent models has been
      difficult to attain; however, the circuitry used by all models is becoming
      increasingly similar. The authors review theoretical and experimental evidence
      for each line of models emphasizing their strengths and weaknesses.

PMID- 14580122
TI  - Glial cells generate neurons--master control within CNS regions: developmental
      perspectives on neural stem cells.
AB  - A common problem in neural stem cell research is the poor generation of neuronal
      or oligodendroglial descendants. The author takes a developmental perspective to
      propose solutions to this problem. After a general overview of the recent
      progress in developmental neurobiology, she highlights the necessity of the
      sequential and hierarchical specification of CNS precursors toward the generation
      of specific cell types, for example, neurons. In the developing as well as the
      adult CNS, multipotent stem cells do not directly generate neurons but give rise
      to precursors that are specified and restricted toward the generation of neurons.
      Some molecular determinants of this fate restriction have been identified during
      recent years and reveal that progression via this fate-restricted state is a
      necessary step of neurogenesis. These discoveries also demonstrate that neuronal
      fate specification is inseparably linked at the molecular level to
      regionalization of the developing CNS. These fate determinants and their specific
      action in distinct region-specific contexts are essential to direct the progeny
      of stem cells more efficiently toward the generation of the desired cell types.
      Recent data are discussed that demonstrate the common identity of precursors and
      stem cells in the developing and adult nervous system as radial glia, astroglia,
      or non-myelinating glia. A novel lineage model is proposed that incorporates
      these new views and explains why the default pathway of stem cells is astroglia.
      These new insights into the cellular and molecular mechanisms of neurogenesis
      help to design novel approaches for reconstitutive therapy of neurodegenerative
      diseases.

PMID- 14580123
TI  - Compartmentation of glutamine, glutamate, and GABA metabolism in neurons and
      astrocytes: functional implications.
AB  - The classical concept regarding compartmentation of brain metabolism pertinent to
      the two neurotransmitter amino acids, glutamate and GABA (gamma-aminobutyrate),
      operates with different pools of glutamate and glutamine in different cell types,
      that is, pools that have different sizes and turnover rates. As a result of more
      sophisticated technology (e.g., nuclear magnetic resonance spectroscopy and mass
      spectrometry used in relation to cultured neurons and astrocytes), a more complex
      scenario is emerging. Hence, both neurons and astrocytes exhibit a
      compartmentalized metabolism that very likely relates to individual cells
      containing mitochondrial populations having different metabolic roles. Models for
      this in neurons and astrocytes, respectively, are presented. The functional
      implications of this for the homeostatic mechanisms regulating the levels of
      neurotransmitter glutamate and GABA are discussed in relation to development of
      therapeutic strategies for neurological disorders in which these transmitters are
      believed to play important roles.

PMID- 14580124
TI  - Prefrontal DA transmission at D1 receptors and the pathology of schizophrenia.
AB  - The current view on the dopamine (DA) hypothesis of schizophrenia postulates a
      cortical/subcortical imbalance: subcortical mesolimbic DA projections might be
      hyperactive, resulting in hyperstimulation of D2 receptors and positive symptoms,
      whereas mesocortical DA projections to the prefrontal cortex might be hypoactive,
      resulting in hypostimulation of D1 receptors, negative symptoms, and cognitive
      impairment. Although the subcortical abnormalities are relatively well
      established now, the evidence for cortical hypodopaminergia is just emerging.
      This article will review current evidence for prefrontal hypodopaminergia in
      schizophrenia, with special emphasis on positron emission tomography (PET)
      studies measuring cortical D1 receptors in schizophrenia. The presentation of the
      clinical data will be introduced by a brief overview of the function of
      prefrontal DA systems, both at the cellular and cognitive level. The impact of
      antipsychotic drugs on prefrontal DA function will also be reviewed. We will
      conclude with the formulation of several models of altered prefrontal DA
      transmission at D1 receptors in schizophrenia.

PMID- 14580125
TI  - William Catterall, Ph.D., of the University of Washington School of Medicine,
      wins Bristol-Myers Squibb neuroscience research award.

PMID- 14580126
TI  - Comorbidities.

PMID- 14580127
TI  - Autism spectrum disorders in children with active epilepsy and learning
      disability: comorbidity, pre- and perinatal background, and seizure
      characteristics.
AB  - The aim of this study was to examine the comorbidity pattern, seizure
      characteristics, and aetiology in a representative group of children with a
      combination of autism spectrum disorder (ASD), active epilepsy, and learning
      disability. Ninety children (47 males, 43 females; mean age 11 years 2 months,
      range 8 to 16 years at the time of psychiatric examination) with active epilepsy
      and learning disability, identified in a population-based study in Goteborg,
      Sweden, were subdivided into those with and those without ASD and compared with
      respect to aetiology, additional neuroimpairments, and seizure characteristics.
      In addition, the cohorts were examined for trends of prevalence over a period of
      time. Results indicated that established aetiology was much more often present in
      the prenatal period than in the peri- or postnatal periods in the ASD group.
      Cerebral palsy and visual impairment were under-represented in the ASD group.
      Partial seizures tended to be more common and generalized seizures less common in
      the ASD group compared with the non-ASD group. Seizure onset was later in the ASD
      group. Many of the significant differences were accounted for by a large group of
      psychiatrically unclassifiable participants in the non-ASD group. There was no
      trend towards an increase of affected children over the 12-year period. There was
      no increase in the prevalence of active epilepsy and learning disability nor in
      the rate of autism with active epilepsy and learning disability in children born
      between 1981 and 1986 compared with those born from 1976 to 1980, indicating no
      statistical association with the general measles-mumps-rubella vaccination
      introduced in the early 1980s.

PMID- 14580128
TI  - Deficient coordination of associated postural adjustments during a lifting task
      in children with neurodevelopmental disorders.
AB  - Precision grip and concomitant anticipatory postural adjustments were
      investigated in 11 children (three females, eight males; mean age 9 years 1
      month, SD 11 months) with attention-deficit-hyperactivity disorder (ADHD); 12
      children (three females, nine males; mean age 9 years, SD 7 months) with
      developmental coordination disorder (DCD), and 13 children (two females, 11
      males; mean age 9 years 9 months, SD 11 months) with a combination of ADHD and
      DCD (ADHD+). There were two comparison groups: an age-matched group (four
      females, 11 males; mean age 9 years 1 month, SD 14 months) and a younger age
      group (five females, six males; mean age 6 years 5 months, SD 8 months).
      Adaptation to different weights was evaluated by lifting a specialized grip
      instrument monitoring grip force, load force, and centre of foot pressure
      displacements. Children with ADHD+ showed: (1) excessive grip forces, (2)
      decreased amplitude and prolonged onset of postural adjustments, and (3) reduced
      ability to adapt the motor output. Children with ADHD and DCD did not scale
      manual and postural forces in amplitude and time domains. Children with DCD also
      differed in delayed timing of postural adjustments. Results indicate that
      children with ADHD and DCD show a spectrum of neural dysfunctions underlying poor
      motor coordination, which are not specific to the clinical disorder.

PMID- 14580129
TI  - Abnormal rhythmic motor response in children with attention-deficit-hyperactivity
      disorder.
AB  - Children with attention-deficit-hyperactivity disorder (ADHD) have difficulties
      with motor control, inhibition of motor responses, motor flexibility, and motor
      preparedness. We proposed that motor abnormalities in ADHD might result, at least
      in part, from an abnormal neuronal oscillatory mechanism necessary for motor
      temporal regulation. The aim of this study was to assess pacing in children with
      ADHD, by testing for rhythmic abnormalities of motor activity using a tapping
      test. Twenty-seven children (21 males, six females; aged 6 to 14 years 6 months;
      mean age 11 years 4 months, SD 2 years 2 months) diagnosed with ADHD according to
      DSM-IV clinical criteria, and 33 controls (25 males, eight females; aged 6 to 14
      years 6 months; mean 11 years 1 month, SD 2 years 2 months), underwent a finger
      tapping test requiring rhythmic responses to frequencies from 1 to 6 Hz. All
      participants who were treated on a daily basis with methylphenidate (n = 22) were
      medication-free on the day of the test. Most of the children with ADHD responded
      at a constant rate regardless of stimulus frequency, a phenomenon only seen in a
      small number of the controls. This specific error pattern, also seen in
      Parkinson's disease, has been attributed to an abnormal oscillatory mechanism
      mediated by dopaminergic fronto-striatal circuitry, which might also be
      pathophysiologically relevant for ADHD.

PMID- 14580130
TI  - Learning of grasp control in children with hemiplegic cerebral palsy.
AB  - This study examined whether children with hemiplegic cerebral palsy (CP) have
      anticipatory control of fingertip forces during lifts of familiar objects, and
      what type of practice (blocked or random) best enhances the retention of
      anticipatory control during lifts of novel objects. Eighteen children with
      hemiplegic CP (7 females, 11 males; 7 to 14 years of age, mean age 10 years, SD
      1.8) and 18 age-matched typically developing children (8 males, 10 females; mean
      age 10.4 years, SD 1.7) participated in the study. In the first experiment the
      children lifted familiar objects of various weights and sizes five times each,
      while the vertical lifting (load) force was measured. Most participants
      demonstrated higher rates of load force increase for heavier (and larger) objects
      already during the first lift, indicating anticipatory control. Furthermore, the
      load force rates generally were similar across the five lifts for each object,
      suggesting that they had stable representations of the objects' properties. In
      the second experiment children lifted three novel objects varying in weight (but
      identical in volume) 27 times each, in either a blocked or a random order,
      followed by nine immediate and nine delayed (24 hours) retention trials. Blocked
      practice resulted in greater differentiation of the force rates between objects
      during acquisition than did random practice. Both practice schedules resulted in
      similar retention. These findings suggest that children with hemiplegic CP have a
      priori internal representations used for anticipatory force scaling with familiar
      objects. Furthermore, the results indicate that these children can form and
      retain internal representations of novel objects for anticipatory control,
      irrespective of the type of practice schedule employed. Thus, clinically based
      practice sessions that incorporate lifts with novel objects may enhance
      anticipatory force scaling and related prehensile function in children with
      hemiplegic CP.

PMID- 14580131
TI  - Botulinum toxin with and without casting in ambulant children with spastic
      diplegia: a clinical and functional assessment.
AB  - This study compared clinical and functional outcomes after treatment with
      botulinum toxin A (BTX-A) and BTX-A with casting in children with dynamic equinus
      foot. Ten children (seven males, three females; mean age 6 years 4 months, SD 2
      years 7 months; range 4 to 11 years) with mild spastic diplegia and independent
      walking were divided into two groups: group 1, BTX-A and group 2, BTX-A plus
      casting. BTX-A was injected in the triceps surae bilaterally at multiple sites
      while the children were sedated with mask anaesthesia. Dysport toxin was used, 15
      to 20 IU/kg in each muscle. Immediately after injection an ankle-foot orthosis
      was applied to children in group 1 and a cast to children in group 2. Clinical
      assessment using the Ashworth scale, Gross Motor Function Measure (GMFM), range
      of movement measurement, and gait analysis was performed before treatment and 1,
      4, and 12 months after treatment. Spasticity decreased significantly at 1-month
      examination in both groups (p = 0.002), at 4-month examinations (Wilcoxon test p
      = 0.003), and 12 month (p = 0.052) examinations in group 2. GMFM highlighted a
      significant improvement in group 2 at the 4-month examination (p = 0.052 for
      standing,p = 0.007 for walking). Gait analysis showed a significant increase in
      the walking speed in group 2 (p = 0.04). No change was detected in ankle
      kinematics and kinetics or in muscular activity during the gait cycle. We
      confirmed that BTX-A reduces spasticity and improves functional performance in
      standing and walking; association with casting provides more marked and enduring
      results.

PMID- 14580132
TI  - Clinical utility of the Duncan-Ely test for rectus femoris dysfunction during the
      swing phase of gait.
AB  - The Ely Test (or Duncan-Ely test) has been accepted as a clinical tool to assess
      rectus femoris spasticity by passively flexing the knee rapidly while the patient
      lies prone in a relaxed state. In this retrospective review, patients' dynamic
      knee range of motion (ROM) during gait and an electromyogram (EMG) were compared
      with the results of the Ely test. Data for 70 patients (44 males, 26 females; 104
      limbs) were included. Mean age of patients was 13 years, SD 9 years, range 4
      years 5 months to 54 years. All patients were diagnosed with cerebral palsy
      (spastic diplegia, n = 42; spastic quadriplegia, n = 15, and hemiplegia, n = 13).
      All patients were ambulatory (50 independent, 20 with assistive devices). A
      standard matrix was used to calculate sensitivity and specificity of the Ely test
      as well as its positive and negative predictive value. For the gait variables
      examined (decreased dynamic knee ROM, timing of peak knee flexion, and abnormal
      EMG in swing) the sensitivity of the Ely test ranged from 56 to 59% and the
      specificity ranged from 64 to 85%. For the same variables the positive predictive
      value ranged from 91 to 98% and the negative predictive value ranged from 4 to
      19%. The Ely test was shown to have a good positive predictive value (i.e. the
      certainty about the presence of rectus spasticity in patients with a positive Ely
      test result) for rectus femoris dysfunction during gait.

PMID- 14580133
TI  - Effects of a topical anesthetic on non-socially maintained self-injurious
      behavior.
AB  - In the present study we hypothesized that the self-injurious behavior (SIB) of a
      12-year-old male diagnosed as having autism and severe mental retardation was
      maintained by automatic reinforcement. Further, we hypothesized SIB served a
      sensory reinforcement function related to sensation at the skin surface. The
      participant engaged in high rates of SIB in the form of self-slapping. A
      functional analysis resulted in undifferentiated findings. Additional
      observations indicated that SIB occurred only to exposed skin surfaces. To test
      for a sensory function, we applied a topical anesthetic to the participant's
      skin. SIB was reduced by 20 to 60% after application of the dermal anesthetic.
      These results support an automatic reinforcement hypothesis. Implications for
      treatment are discussed.

PMID- 14580134
TI  - Conscious visual abilities in a patient with early bilateral occipital damage.
AB  - A 21-year-old male presented with occipital lobes that were extensively damaged
      by bilateral infarcts present at birth. The absence of the striate cortex was
      confirmed with anatomic and functional MRI and high-resolution EEG. His cortical
      visual impairment was severe, but he retained a remarkable ability to see fast
      moving stimuli. Horizontal optokinetic nystagmus could be elicited from either
      eye. Resolution acuity was close to normal providing the patient was allowed to
      move his head and eyes. The direction of motion in random-dot patterns could be
      discriminated with perfect accuracy at speeds above 2 deg/s, and the patient
      reported that he could 'see' the motion at fast but not at slow speeds. This
      conscious residual vision for motion is known as Riddoch's phenomenon, but it has
      never been reported in the complete absence of the striate cortex. Functional
      neuroimaging revealed activation that was outside the motion-responsive regions
      of the extrastriate cortex. This case demonstrates remarkable plasticity in the
      human visual system and may have implications for understanding the functional
      organization of the motion pathways.

PMID- 14580135
TI  - Pyridoxine-dependent seizures and cognition in adulthood.
AB  - A case report of neonatal onset pyridoxine-dependent seizures in a male patient
      with early diagnosis and treatment is presented. The patient's epilepsy was
      recognized and treated with pyridoxine (vitamin B6) within 8 hours of birth.
      Treatment has been nearly continuous since that time. This paper reports the
      results of a full neuropsychological evaluation at age 37 years and MRI completed
      at age 31 years. Consistent with other case reports in the literature, there was
      a significant Performance IQ (PIQ) advantage with decreased Verbal IQ (VIQ) and
      expressive language skills (Full-Scale IQ 71, VIQ 64, PIQ 85). MRI demonstrated
      characteristic thinning of the posterior corpus callosum. This report provides an
      example of early treatment that nonetheless results in a mild mental retardation.
      The similarity of the structural changes on MRI and the cognitive profile of this
      patient to those of others reported in the literature suggest that the underlying
      mechanism for both may be the same.

PMID- 14580136
TI  - Ambulatory capacity in cerebral palsy: prognostic criteria and consequences for
      intervention.
AB  - In conclusion, although the importance of encouraging the development of physical
      abilities remains, in certain cases we cannot simply wait for years to see
      whether a child will eventually become an effective walker as a result of
      physiotherapy or orthopaedic interventions. Powered mobility should be considered
      as a means of providing efficient, autonomous locomotion for children with severe
      motor disabilities, so enabling them to become more active participants in their
      own lives rather than remaining spectators. Children with moderate levels of
      motor impairment could be encouraged to see wheelchair use as beneficial in some
      circumstances and not an irreversible failure.

PMID- 14580137
TI  - War with Scotland?

PMID- 14580138
TI  - Face detection: mapping human performance.
AB  - The recognition of faces has been the focus of an extensive body of research,
      whereas the preliminary and prerequisite task of detecting a face has received
      limited attention from psychologists. Four experiments are reported that address
      the question how we detect a face. Experiment 1 reveals that we use information
      from the scene to aid detection. In experiment 2 we investigated which features
      of a face speed the detection of faces. Experiment 3 revealed inversion effects
      and an interaction between the effects of blurring and reduction of contrast. In
      experiment 4 the sizes of effects of reversal of orientation, luminance, and hue
      were compared. Luminance was found to have the greatest effect on reaction time
      to detect faces. The results are interpreted as suggesting that face detection
      proceeds by a pre-attentive stage that identifies possible face regions, which is
      followed by a focused-attention stage that employs a deformable template.
      Comparisons are drawn with automatic face-detection systems.

PMID- 14580139
TI  - The role of facial colour and luminance in visual and audiovisual speech
      perception.
AB  - We conducted four experiments to investigate the role of colour and luminance
      information in visual and audiovisual speech perception. In experiments 1a
      (stimuli presented in quiet conditions) and 1b (stimuli presented in auditory
      noise), face display types comprised naturalistic colour (NC), grey-scale (GS),
      and luminance inverted (LI) faces. In experiments 2a (quiet) and 2b (noise), face
      display types comprised NC, colour inverted (CI), LI, and colour and luminance
      inverted (CLI) faces. Six syllables and twenty-two words were used to produce
      auditory and visual speech stimuli. Auditory and visual signals were combined to
      produce congruent and incongruent audiovisual speech stimuli. Experiments 1a and
      1b showed that perception of visual speech, and its influence on identifying the
      auditory components of congruent and incongruent audiovisual speech, was less for
      LI than for either NC or GS faces, which produced identical results. Experiments
      2a and 2b showed that perception of visual speech, and influences on perception
      of incongruent auditory speech, was less for LI and CLI faces than for NC and CI
      faces (which produced identical patterns of performance). Our findings for NC and
      CI faces suggest that colour is not critical for perception of visual and
      audiovisual speech. The effect of luminance inversion on performance accuracy was
      relatively small (5%), which suggests that the luminance information preserved in
      LI faces is important for the processing of visual and audiovisual speech.

PMID- 14580140
TI  - Prior knowledge about display inversion in biological motion perception.
AB  - Display inversion severely impedes veridical perception of point-light biological
      motion (Pavlova and Sokolov, 2000 Perception & Psychophysics 62 889-899; Sumi,
      1984 Perception 13 283-286). Here, by using a spontaneous-recognition paradigm,
      we ask whether prior information about display orientation improves biological
      motion perception. Participants were shown a set of 180 degrees inverted point
      light stimuli depicting a human walker and quadrupeds (dogs). In experiment 1,
      one group of observers was not aware of the orientation of stimuli, whereas the
      other group was told beforehand that stimuli will be presented upside down. In
      experiment 2, independent groups of participants informed about stimulus
      orientation saw the same set of stimuli, in each of which either a moving or a
      static background line was inserted. The findings indicate that information about
      display inversion is insufficient for reliable recognition of inverted point
      light biological motion. Instead, prior information facilitates display
      recognition only when it is complemented by additional contextual elements. It
      appears that visual impressions from inverted point-light stimuli remain
      impenetrable with respect to one's knowledge about display orientation. The
      origins of orientation specificity in biological motion perception are discussed
      in relation to the recent neuroimaging data obtained with point-light stimuli and
      fragmented Mooney faces.

PMID- 14580141
TI  - The relationship between change detection and recognition of centrally attended
      objects in motion pictures.
AB  - Observers typically detect changes to central objects more readily than changes
      to marginal objects, but they sometimes miss changes to central, attended objects
      as well. However, even if observers do not report such changes, they may be able
      to recognize the changed object. In three experiments we explored change
      detection and recognition memory for several types of changes to central objects
      in motion pictures. Observers who failed to detect a change still performed at
      above chance levels on a recognition task in almost all conditions. In addition,
      observers who detected the change were no more accurate in their recognition than
      those who did not detect the change. Despite large differences in the
      detectability of changes across conditions, those observers who missed the change
      did not vary in their ability to recognize the changing object.

PMID- 14580142
TI  - The line-motion illusion can be reversed by motion signals after the line
      disappears.
AB  - In the line-motion illusion, a briefly flashed line appears to propagate from the
      locus of attention, despite being physically presented on the screen all at once.
      It has been proposed that the illusion reflects low-level visual information
      processing that occurs faster at the locus of attention (Hikosaka et al 1993
      Vision Research 33 1219-1240; Perception 22 517-526). Such an explanation
      implicitly embeds the assumption that speeding or slowing of neural signals will
      map directly onto perceptual timing. This 'online' hypothesis presupposes that
      signals which arrive first are perceived first. However, other evidence suggests
      that events in a window of time after the disappearance of a visual stimulus can
      influence the brain's interpretation of that stimulus (Eagleman and Sejnowski
      2000 Science 287 2036-2038; 289 1107a; 290 1051a; 2002 Trends in Neuroscience 25
      293). If the online hypothesis were true, we should expect that events occurring
      after the flashing of the line would not change the illusion. Consistent with our
      hypothesis that awareness is an a posteriori reconstruction, we demonstrate that
      the perceived direction of illusory line-motion can be reversed by manipulating
      stimuli after the line has disappeared.

PMID- 14580143
TI  - Efficient extrapolation of the view with a dynamic and predictive stimulus.
AB  - In the real-world, the retinal projection of an object changes as we move, or as
      a moving object passes in front of us. We have to recognise objects, despite such
      retinal-projection changes. Many studies have shown that the time required to
      identify objects after a change in the retinal projection is longer than when
      there is no retinal-projection change. This recognition cost is referred to as
      the view-dependent effect. Previous researchers have studied the view-dependent
      effect while disregarding the predictability of retinal-projection changes. Here,
      we demonstrate that there is no view-dependent effect when the predictability is
      introduced, in the case where participants track moving objects by head-turning
      or eye-movement in a virtual environment. Violation of the predictability, such
      as an unpredictable retinal-projection change or a movement of the first stimulus
      that was inconsistent with a subsequent retinal-projection change, caused a view
      dependent effect. Moreover, we found that extraretinal information such as head
      turning or eye-movement was unnecessary for view-independent recognition. These
      results indicate that humans can extrapolate to the tested view from the studied
      view in a view-independent way when retinal-projection change is predictable from
      the visual stimulus.

PMID- 14580144
TI  - Boundary completion in illusory contours: interpolation or extrapolation?
AB  - Most computational and neural-style models of contour completion (ie illusory and
      occluded contours) are based on interpolation: the filling in of an edge between
      two visible edges. The results of three experiments suggest an alternative
      conception, that units are formed as a result of extrapolation from visible
      edges. In three experiments, subjects reported illusory contours between standard
      illusory-contour inducing elements and forms that do not, by themselves, induce
      illusory contours. We suggest that these forms are not a special case of inducing
      elements but that they represent a different class--receiving elements. Receiving
      elements are forms that can receive an illusory contour but cannot generate one,
      and they can alter contour formation. In experiment 1, receiving elements
      increased the judged clarity of illusory contours. In experiment 2, illusory
      edges were seen to connect to corners, line ends, and even the edges of circles.
      Boundary formation in motion displays also appears to be based on extrapolation.
      In experiment 3, subjects reported that small moving dots altered the formation
      of spatiotemporally defined boundaries. Implications for higher-order operator
      and network models of boundary formation are discussed.

PMID- 14580145
TI  - Illusory illusions: the significance of fixation on the perception of geometrical
      illusions.
AB  - Some well-known geometrical illusions disappear when the eyes are fixating and
      saccades are suppressed for a period of time. This disappearance is not
      accompanied by fading due to stabilisation of the retinal image. Any saccade made
      on purpose restores the illusion immediately. The fixation time after which some
      illusions disappeared was measured for four illusions and four subjects each.
      Effects of practice have been observed after measurements were repeated on
      successive days. Present theories of vision cannot readily explain the effect.

PMID- 14580146
TI  - Monocular discs in the occlusion zones of binocular surfaces do not have
      quantitative depth--a comparison with Panum's limiting case.
AB  - Da Vinci stereopsis is defined as apparent depth seen in a monocular object
      laterally adjacent to a binocular surface in a position consistent with its
      occlusion by the other eye. It is widely regarded as a new form of quantitative
      stereopsis because the depth seen is quantitatively related to the lateral
      separation of the monocular element and the binocular surface (Nakayama and
      Shimojo 1990 Vision Research 30 1811-1825). This can be predicted on the basis
      that the more separated the monocular element is from the surface the greater its
      minimum depth behind the surface would have to be to account for its monocular
      occlusion. Supporting evidence, however, has used narrow bars as the monocular
      elements, raising the possibility that quantitative depth as a function of
      separation could be attributable to Panum's limiting case (double fusion) rather
      than to a new form of stereopsis. We compared the depth performance of monocular
      objects fusible with the edge of the surface in the contralateral eye (lines) and
      non-fusible objects (disks) and found that, although the fusible objects showed
      highly quantitative depth, the disks did not, appearing behind the surface to the
      same degree at all separations from it. These findings indicate that, although
      there is a crude sense of depth for discrete monocular objects placed in a valid
      position for uniocular occlusion, depth is not quantitative. They also indicate
      that Panum's limiting case is not, as has sometimes been claimed, itself a case
      of da Vinci stereopsis since fusibility is a critical factor for seeing
      quantitative depth in discrete monocular objects relative to a binocular surface.

PMID- 14580147
TI  - The availability of large size from shadow: looking for hidden assumptions.

PMID- 14580148
TI  - The heme oxygenase dilemma in cellular homeostasis: new insights for the feedback
      regulation of heme catabolism.
AB  - Heme must be synthesized and degraded within an individual nucleated cell. Heme
      degradation is catalyzed by the two isozymes of heme oxygenase, heme oxygenase-1
      (HO-1) and HO-2, eventually yielding biliverdin/bilirubin, CO, and iron. These
      products possess important physiological roles but are potentially toxic to
      cells. Characteristically, human HO-1 contains no Cys residues, whereas HO-2
      contains the potential heme-binding motifs of the Cys-Pro dipeptide. Expression
      of HO-1 is inducible or repressible, depending on cell types or cellular
      microenvironments, but expression levels of HO-2 are fairly constant. Thus, the
      main regulation of heme catabolism is a problem of the balance between induction
      and repression of HO-1. Notably, HO-1 expression is induced by heme in all
      mammalian cells examined, but is repressed by hypoxia in certain types of
      cultured human cells. The recent discovery of Bach1 as a heme-regulated and
      hypoxia-inducible repressor for transcription of the HO-1 gene has provided a
      missing link in the feedback control of heme catabolism. On the other hand, the
      human HO-1 gene promoter contains the (GT)n repeat polymorphism and a single
      nucleotide polymorphism (-427A --> T), both of which may contribute to fine
      tuning of the transcription. Importantly, long (GT)n alleles are associated with
      susceptibility to smoking-induced emphysema or coronary artery disease, but may
      provide with resistance to cerebral malaria. The latter finding suggests a novel
      therapeutic strategy with inhibitors of HO-1 for the treatment of cerebral
      malaria. We discuss the potential regulatory role of Bach1 and HO-2 in heme
      catabolism and update the understanding of the regulation of HO-1 expression.

PMID- 14580150
TI  - Involvement of poly(ADP-ribose) synthetase in acoustic trauma of the cochlea.
AB  - We investigated effects of poly(ADP-ribose) synthetase (PARS) inhibitors on
      acoustic trauma. Albino guinea pigs were intravenously given 3-aminobenzamide,
      nicotinamide or 3-aminobenzoic acid (an inactive analog of 3-aminobenzamide) just
      prior to exposure to a 2 kHz pure tone of 120 dB sound pressure level (SPL) for
      10 minutes. The threshold of the compound action potential (CAP) and the
      amplitude of distortion-product otoacoustic emissions (DPOAEs) were measured
      before and 4 hours after the acoustic overexposure. Statistically significant
      decreases in the CAP threshold shifts and significant increases in the DPOAE
      amplitudes were observed 4 hours after the acoustic overexposure in the animals
      treated with 3-aminobenzamide or nicotinamide, whereas 3-aminobenzoic acid did
      not exert any protective effect. These results strongly suggest that excessive
      activation of PARS is involved in generation of the acoustic trauma.

PMID- 14580149
TI  - Effect of hypoxia on the expression of fractalkine in human endothelial cells.
AB  - CX3CL1/fractalkine is a chemokine with a unique CX3C motif. Hypoxia mediates the
      expression of various genes, such as vascular endothelial growth factor (VEGF),
      cyclooxygenase-2, and plasminogen-activator inhibitor-1, in vascular endothelial
      cells. We studied the effect of hypoxia on the expression of fractalkine induced
      by interferon-gamma (IFN-gamma) in endothelial cells. Human umbilical vein
      endothelial cells were cultured, and the stimulation of the cells with IFN-gamma
      was found to induce the expression of fractalkine. Hypoxia inhibited the
      expression of fractalkine mRNA and protein by IFN-gamma, and this effect was
      observed with concomitant increase in VEGF expression. Desferrioxamine, an iron
      chelator that mimics hypoxia in vitro, also inhibited the fractalkine production
      induced by IFN-gamma. Hypoxia did not affect the degradation of fractalkine mRNA.
      The inhibition of fractalkine expression by hypoxia was reversed on returning the
      cultures to reoxygenation condition. Inhibition of IFN-induced fractalkine
      expression by hypoxia was not affected by the presence of a radical scavenger, N
      acetyl-L-cysteine, and the involvement of reactive oxygen species may be
      excluded. Inhibition of fractalkine expression by hypoxia may be involved in the
      pathophysiology of ischemic diseases.

PMID- 14580151
TI  - Green tea polyphenol (-)-epigallocatechin gallate prevents oxidative damage on
      periventricular white matter of infantile rats with hydrocephalus.
AB  - Hydrocephalus causes damage to periventricular white matter at least in part
      through chronic ischemia. Emphasizing the periventricular ischemia/hypoxia in
      hydrocephalus, various authors indicated the secondary biochemical impairment and
      oxidative damage in experimentally induced and congenital hydrocephalic rat
      brain. (-)-Epigallocatechin gallate (EGCG), the main constituent of green tea
      polyphenols, has been shown to be of some protective value in various models of
      neurological injury as a free oxygen radical scavenger. In the present study the
      effects of EGCG were examined on the periventricular oxidative damage in
      experimental childhood-onset hydrocephalus. Hydrocephalus was induced in 3 weeks
      old rat pups by kaolin injection into the cisterna magna. A single daily dose of
      50 mg/kg of EGCG injected into the peritoneum of the rats for 15 days
      significantly reduced periventricular white matter malondialdehyde levels when
      compared to non-treated hydrocephalic animals. Our results indicate that EGCG may
      have a protective effect against periventricular white matter oxidative damage in
      hydrocephalus induced infantile rats.

PMID- 14580152
TI  - A novel GT-mismatch binding protein that recognizes strict DNA sequences with
      high affinity.
AB  - Mismatched or damaged base pairs in DNA are mutagenic and both eukaryotes and
      prokaryotes have a series of repair systems that decrease a spontaneous mutation
      rate. All exocyclic amino groups of cytosine(C), adenine(A), and guanine(G)
      contribute to hydrogen bonds for base pairing. High temperature and oxidative
      stresses increase the deamination of these bases and methylated C. These
      deaminated sites would be initially recognized by components of DNA repair
      system. We discovered a novel G/thymine(T)-mismatch binding protein (nGTBP) that
      bound, with high affinity, to a minimal 14-mer DNA heteroduplex with a strict 5'
      TRT GNB-3' sequence (R for purine, N for any bases, and B for "not A," namely for
      C, G, or T ). This italicized G position mismatched with T could be replaced by
      hypoxanthine, the deaminated A. The nGTBP, however, barely recognized DNA
      duplexes individually containing 8-oxo-G, thymine glycol, and 5-methylcytosine.

PMID- 14580153
TI  - Mitochondrial oxidative stress and mitochondrial DNA.
AB  - Mitochondria produce reactive oxygen species (ROS) under physiological conditions
      in association with activity of the respiratory chain in aerobic ATP production.
      The production of ROS is essentially a function of O2 consumption. Hence,
      increased mitochondrial activity per se can be an oxidative stress to cells.
      Furthermore, production of ROS is markedly enhanced in many pathological
      conditions in which the respiratory chain is impaired. Because mitochondrial DNA,
      which is essential for execution of normal oxidative phosphorylation, is located
      in proximity to the ROS-generating respiratory chain, it is more oxidatively
      damaged than is nuclear DNA. Cumulative damage of mitochondrial DNA is implicated
      in the aging process and in the progression of such common diseases as diabetes,
      cancer, and heart failure.

PMID- 14580154
TI  - The new European directive on in vitro diagnostics.
AB  - The Directive on in vitro Diagnostic Medical Devices (IVDD 98/79/EC) was
      officially adopted by the European Union (EU) on December 7, 1998. The IVDD aims
      to supplement the legal framework of the European Community, which governs the
      conditions for the placing on the market of medical devices, by extending the
      already implemented legislation to the category of in vitro diagnostic medical
      devices (IVDs). They consist of those devices, including reagents and reagent
      products, calibrator materials or instruments, as well as specimen receptacles,
      intended by the manufacturer for the in vitro analysis of specimens derived from
      the human body. This directive has introduced at the European level common
      regulatory requirements across Europe for the safety, quality and performance of
      in vitro diagnostics (IVDs), incorporating them into medical device legislation.
      It harmonizes the conformity assessment procedures to be applied by manufacturers
      before they place IVDs on the market. For certain products expressly specified in
      the directive, of which the most important are used for the evaluation of the
      safety of blood supply and patient testing, the manufacturer will have to take
      into account in their performance evaluation the so-called "Common Technical
      Specifications" (CTS). These are needed to establish the performance
      characteristics of the IVDs in evaluation and have the same status as harmonized
      standards. In the meantime, the IVD directive has been transposed into national
      law in all EU countries. During a transitional period ending in December 2003,
      manufacturers will have the option of following pre-existing national regulatory
      processes or taking their IVDs through the new procedures as specified in the
      directive. Following this, starting from 7th December 2003, adherence to the
      directive regulations will become mandatory, and only IVDs bearing the
      "Communautes Europeennes (CE) mark" can then be sold in the EU.

PMID- 14580155
TI  - Two MMP-2 promoter polymorphisms (-790T/G and -735C/T) in chronic heart failure.
AB  - Remodelling of extracellular matrix by activated matrix metalloproteinases is
      considered to contribute to progression of ventricle remodelling during chronic
      heart failure. The aim of this study was to associate two promoter polymorphisms,
      -790T/G and -735C/T, in the gene for matrix metalloproteinase (MMP)-2 (gelatinase
      A) with chronic heart failure (CHF). For this purpose, 164 patients (124 men, 40
      women, median age 56 years, range 21-91 years) with CHF (functional class NYHA II
      IV, ejection fraction median 25%, cardiothoracic index more than 50%) were
      compared with 196 control subjects without clinical signs of cardiovascular
      disease (131 men and 65 women, median age 56 years, range 27-84 years) in -790T/G
      and -735C/T MMP-2 genotype distributions and allelic frequencies. The genotypes
      were determined by polymerase chain reaction (PCR) with restriction analyses. A
      significant increase of the T allele of the -790T/G MMP-2 polymorphism (p =
      0.04), as well as of the C allele of the -735C/T MMP-2 gene polymorphism, in
      patients with CHF was proven (p = 0.04). The heterozygote CT of the -735C/T MMP-2
      polymorphism exhibits a 7 times higher odds ratio (OR) for the CHF patients with
      lower levels of total cholesterol (less than 5 mmol/l), especially for non
      hypertensive CHF men (OR = 7.28, 95% confidence interval 1.51-35.03, p = 0.006).
      Determination of MMP polymorphisms in the regulatory area of the gene could help
      us to comprehend individual susceptibility of patients with CHF to MMP inhibitors
      based on known risks of MMP genotypes.

PMID- 14580156
TI  - A common truncated variant of lipoprotein lipase in the Japanese population is
      characterized by pattern B phenotype.
AB  - To investigate the relationship between the lipoprotein lipase Ser447Ter (S447X)
      mutation, lipid profiles and risk of atherosclerotic disease, we studied two
      groups of Japanese subjects. These groups consisted of a dyslipidemic group
      (triglyceride (TG) > 1.69 mmol/l and high-density lipoprotein-cholesterol (HDL-C)
      < or = 0.91 mmol/l; n = 106) and a control group (TG < or = 1.69 mmol/l and HDL-C
      > or = 1.16 mmol/l; n = 106). All subjects in the control group were confirmed to
      the pattern A phenotype (normal low-density lipoprotein (LDL) pattern), and 21
      individuals in this group were heterozygous for the S447X mutation, but not
      homozygous. In the patient group, pattern A was shown by 44 of 106 patients. The
      rest were of the pattern B phenotype, which is associated with an increased risk
      of coronary heart disease. Homozygosity was concentrated in the patient group (p
      < 0.05) and in those with the pattern B phenotype (p < 0.05). In contrast,
      heterozygosity between both groups was not statistically significant. In
      conclusion, heterozygous and homozygous status with respect to the LPL S447X
      mutation appears to have different meanings with respect to biochemical and
      clinical phenotypes of atherosclerosis.

PMID- 14580157
TI  - Effects of acute, heavy-resistance exercise on urinary peptide hormone excretion
      in humans.
AB  - To examine physical exercise-related changes in urinary excretion of
      protein/peptide hormones and to correlate modifications with the general increase
      in post-exercise proteinuria, urine C-peptide, insulin and insulin-like growth
      factor-I (IGF-I) and their plasma concentrations were measured. Plasma and
      urinary C-peptide, insulin and IGF-I before (Bex) and at the end (Eex) of
      physical exercise (a 2.5-hour competition, 102 km) were analysed in 20 young
      cyclists. At Eex compared with Bex, concentration of urinary C-peptide decreased
      slightly but significantly (21.3 +/- 2.7 vs. 13.5 +/- 1.7 nmol/l), but urinary
      insulin and urinary IGF-I concentrations significantly increased at Eex (92.5 +/-
      4.2 vs. 131.4 +/- 15.7 pmol/l and 10.0 +/- 2.1 vs. 33.6 +/- 3.8 pmol/l,
      respectively). Plasma insulin and plasma C-peptide significantly decreased,
      whereas plasma IGF-I was unchanged. Urinary concentrations of total proteins and
      creatinine significantly increased. Both Eex urinary C-peptide/urinary protein
      and urinary C-peptide/urinary creatinine ratios were significantly reduced. The
      correlation between C-peptide and insulin in plasma was confirmed at Bex as well
      as Eex, but in urine only at Bex. An increased renal tubular reabsorption of C
      peptide at the end of exercise might be suggested, but the expected values
      considering creatinine excretion were almost three times less. The Eex urinary
      insulin concentration was higher than expected, considering the circulation
      levels, but lower when compared with the expected concentration considering
      creatinine excretion. Physical exercise proteinuria, related to an increased
      protein filtration and a saturation of the mechanisms responsible for the
      reabsorption, does not appear similar for all peptide hormones.

PMID- 14580158
TI  - HMG-CoA reductase inhibitors are associated with decreased serum neopterin levels
      in stable coronary artery disease.
AB  - Neopterin, a marker of stimulated cellular immune response, is increased in
      unstable angina, acute myocardial infarction and possibly stable coronary artery
      disease. 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors
      (statins) have anti-inflammatory properties, but their effect on neopterin is
      largely unknown. Neopterin was measured in 232 patients undergoing elective
      coronary angiography and compared to the degree of atherosclerosis, use of
      concomitant medications and demographics. Neopterin was lower in subjects using
      statins (n = 66) compared to those not taking statins (median (range): 6.65 (4.1
      18.3) vs. 7.70 (3.6-29.1) nmol/l, p < 0.0001). This association was also found in
      the subgroup of patients with coronary artery disease (1-3-vessel disease, n =
      164; 6.60 (4.1-18.3) vs. 7.80 (3.6-29.1) nmol/l, p = 0.0012), whereas only a
      slight tendency toward lower neopterin levels was found in the group without
      atherosclerosis (6.90 (5.1-16.0) vs. 7.60 (4.0-18.5) nmol/l, p = 0.17). In
      patients with coronary atherosclerosis, neopterin concentrations were lower in
      smokers (n = 105) compared to non-smokers (7.20 (3.6-29.1) vs. 7.90 (4.4-18.6)
      nmol/l, p < 0.02), confirming previous observations. However, use of statins was
      associated with lower neopterin levels in both non-smokers and smokers (6.70 (4.1
      18.3) vs. 7.60 (3.6-29.1) nmol/l, p < 0.05, and 6.20 (5.2-16.0) vs. 7.80 (4.4
      18.6) nmol/l, p < 0.05, respectively). Overall, similar serum neopterin
      concentrations were found in patients with coronary atherosclerosis and those
      without. In accordance with their anti-inflammatory effects, the use of statins
      is associated with lower neopterin levels in patients undergoing elective
      coronary angiography.

PMID- 14580159
TI  - Impairment of blood-brain barrier integrity during carotid surgery as assessed by
      serum S-100B protein concentrations.
AB  - During carotid endarterectomy (CEA) the internal carotid artery is cross-clamped
      for a period of several minutes. This maneuver may cause cerebral hypoperfusion
      and/or impairment of the blood-brain barrier (BBB) even in cases where clinical
      signs are absent. The aim of the present study was to examine whether such
      alterations could be detected by monitoring the cerebral marker S-100B protein
      concentrations during and after CEA in the serum. Twenty-five consecutive
      patients (17 M/8 F, mean age: 64.2 years, range 47-79 years) undergoing elective
      CEA at our department were studied. All of these patients were without
      perioperative neurological deficit. Intraoperative samples were collected from
      internal jugular and peripheral venous blood: 1) before carotid cross-clamping;
      2) immediately before declamping; 3) after clamp release. Postoperative samples
      were taken from peripheral blood at 6 and 24 h, respectively. S-100B was assayed
      in sera using an immunoluminometric technique. During carotid cross-clamping, S
      100B protein concentrations in the ipsilateral jugular serum significantly (p <
      0.02) increased to pre-clamp values. After declamping, however, S-100B returned
      to the baseline level. No differences were seen between the responses of
      hypertensive and normotensive patients. There was no correlation between carotid
      occlusion time and S-100B protein concentrations. In the peripheral venous serum
      no significant changes in S-100B concentrations were detected during or after
      CEA. We presume that the elevation of S-100B protein concentration during CEA in
      patients with no neurological deficits indicates the transient opening of the BBB
      elicited by carotid cross-clamping.

PMID- 14580160
TI  - Characteristics of prolidase from the erythrocytes of normal humans and patients
      with prolidase deficiency and their mother.
AB  - Prolidases I and II were highly purified from human erythrocytes. The effects of
      various amino acids, MnCl2 and mercaptoethanol, on these two enzymes were
      investigated. Normal prolidase II was very labile in the absence of MnCl2 or
      mercaptoethanol. The activity of prolidase II was maintained at about 76% by pre
      incubation with MnCl2; it was then activated up to 140% by treatment with
      mercaptoethanol for 60 minutes at 37 degrees C. Normal prolidases I and II showed
      the highest activity against glycylproline or methionylproline in the presence of
      MnCl2. The activity of prolidase I against glycylproline was enhanced strongly by
      glycine and MnCl2, but not activated in the absence of MnCl2. The activity of
      prolidase II against methionylproline was enhanced three-fold in the presence of
      glycine and MnCl2, but its activity against glycylproline was very low even in
      the presence of MnCl2. A stronger enhancement of this activity was found in
      normal erythrocytes, and a lower level of this activity was found in erythrocytes
      of patients treated with glycine, MnCl2 and mercaptoethanol compared to those
      treated with glycine and MnCl2. The activity of prolidase II against
      methionylproline in all erythrocytes, of normal humans and of patients, was
      strongly activated by the addition of glycine with MnCl2 but suppressed by the
      addition of mercaptoethanol.

PMID- 14580161
TI  - Reference levels of insulin-like growth factor I in the serum of healthy adults:
      comparison of four immunoassays.
AB  - The measurement of insulin-like growth factor-I (IGF-I) has become an essential
      tool for diagnosing growth hormone deficiency and acromegaly, as well as for
      monitoring the efficacy of treatment in these disorders. The latter aspect gains
      significance in the light of epidemiological studies which indicate a
      relationship between IGF-I levels and the incidence of certain malignancies. We
      aimed to evaluate the performance of widely implemented IGF-I assays by testing
      four representative, commercially available immunoassays. Thus, four parallel
      determinations of the IGF-I levels of 427 healthy blood donors aged between 18
      and 79 years were conducted. Apart from divergent performance criteria, the
      assays also differed systematically. These differences were, however, linear and
      of lower magnitude among the lower ranges. We conclude that despite the wide
      variance among commercially available IGF-I assays, which principally involve
      assay-specific normative data, each of the implemented assays was robust and thus
      an appropriate tool in the diagnostic work-up of growth hormone deficiency in
      adult life, when IGF-I levels are low.

PMID- 14580162
TI  - Age-specific analysis of normal cytokine levels in healthy infants.
AB  - While pathophysiology of elevated cytokines is well delineated, reference values
      for children are unknown, although they may vary physiologically with age and
      differ from those of adults. Between June and November 2001, interleukin (IL)-6,
      IL-10 and tumor necrosis factor-alpha (TNF-alpha) concentrations from blood
      samples of 79 healthy children in six different age groups (group I: 0-3 months;
      group II: 4-12 months; group III: 13-24 months; group IV: 25-36 months; group V:
      37-48 months; group VI: 49-60 months) were measured with ELISA. TNF-alpha was
      within 2.2-3.5 pg/ml in all groups with a trend toward higher values in groups II
      and III (p = ns). IL-6 was significantly lower in group III than in groups IV (p
      = 0.0165) and VI (p = 0.0147). IL-10 was within 3.3-5.5 pg/ml in all groups (p =
      ns). In regression analysis no correlation between age and cytokine
      concentrations was found. Although not statistically significant, IL-6 was lower
      and TNF-alpha higher than the adult reference values provided by the kit
      manufacturer. Although reference cytokine levels seem not age-related during
      early infancy, IL-6 is significantly lower during the second year of life than
      later. In infants aged 5 years or younger, reference levels of IL-6 should be
      chosen lower, and those of TNF-alpha higher, than the adult reference values.

PMID- 14580163
TI  - Differences between genotyping and phenotyping methods for assessing
      apolipoprotein(a) size polymorphisms.
AB  - The aim of the present study was to analyze, on a double-blind basis, the
      relationships between the apolipoprotein(a) (apo(a)) gene and protein size
      polymorphisms in healthy volunteers (n = 99) and patients with premature
      myocardial infarction (n = 91). Apo(a) genotypes were determined by pulse-field
      electrophoresis and phenotypes were separated by sodium dodecyl sulfate-agarose
      gel electrophoresis. Results showed that phenotyping overestimated apo(a) size
      with respect to genotyping (mean (SD) = 3.7 (3.4) kringle units; p < 0.001) in
      subjects with a double-band genotype, although both measurements were highly
      correlated (r = 0.83; p < 0.001). We also observed that the protein band in
      subjects with a single-band phenotype was related more closely to the smallest
      allele than to the largest allele band. The correlation of plasma lipoprotein(a)
      (Lp(a)) concentration was stronger with the phenotype than with the genotype. We
      hypothesize that post-translational modifications in the apo(a) molecule may be
      the most plausible explanation for the discrepancies observed. In conclusion, the
      present study highlights the dissimilarities between phenotyping and genotyping
      methods for the measurement of apo(a) size and suggests that laboratories should
      carefully consider these relationships and the transfer of results between such
      methodologies.

PMID- 14580164
TI  - CYP3A4 and MDR1 alleles in a Portuguese population.
AB  - Polymorphisms in cytochrome P450 CYP3A4 and multidrug resistance (MDR) 1 genes
      coding for the important drug-metabolising CYP3A4 and the ATP-binding cassette
      (ABC) transporter P-glycoprotein (Pgp) are poorly documented in the Portuguese
      population. In this study we have determined the frequencies of CYP3A4 and MDR1
      alleles in Portuguese Caucasians. Both genes were simultaneously analysed as
      these genes are known to be frequently co-induced and their products to show a
      pronounced overlap of substrates. CYP3A4 A-392G (CYP3A4*1B), T673C (CYP3A4*2) and
      MDR1 T-129C, G2677T and C3435T single nucleotide polymorphisms (SNPs) were
      analysed in 100 individuals from the southern region of the country. We observed
      a frequency of 4.0% for CYP3A4*1B, not significantly different from that reported
      on other Caucasian European populations. CYP3A4*2 was found at an allele
      frequency of 4.5%, constituting the first report of the presence of this allele
      outside the Finnish population. Significant differences were found concerning the
      MDR1 C3435T SNP frequency (64.5%) compared with other European populations, while
      no differences were found concerning G2677T (47.5%) or T-129C (5%) SNPs. Linkage
      between the C3435T and G2677T SNPs was observed, although not as evidently as
      documented in other Caucasian populations. No preferential associations were
      detected between CYP3A4 and MDR1 alleles.

PMID- 14580165
TI  - Common variants in the lipoprotein lipase gene in Brazil: association with lipids
      and angiographically assessed coronary atherosclerosis.
AB  - Lipoprotein lipase is the rate-limiting enzyme in the lipolysis of plasma
      triglyceride-rich lipoproteins. We studied six variants (T-93G, D9N, N291S,
      PvuII, HindIII and S447X) in the lipoprotein lipase (LPL) gene in 309 non
      diabetic patients with angiographically assessed coronary artery disease and in
      197 controls in a southern Brazilian population of European descent. The HindIII
      H-allele was associated with lower triglycerides (p < 0.01) and higher high
      density lipoprotein cholesterol (p = 0.03) levels, and the S447X mutation was
      associated with lower triglyceride levels (p < 0.01) in males, but not females.
      No other significant lipid associations were observed. Haplotypes were derived
      from these two sites (HindIII/S447X), and carriers of H-S and H-X haplotypes
      showed lower triglycerides (p < 0.01) and increased high-density lipoprotein
      cholesterol (p = 0.01) levels when compared to the H+S haplotype in males. In
      this gender, the H-X haplotype was associated with a protective effect (OR =
      0.36, 95%CI = 0.13-0.97) for significant disease (> or = 60% of luminal coronary
      stenosis), even controlling for other classical risk factors.

PMID- 14580166
TI  - The risk of venous thromboembolism associated with the factor V Leiden mutation
      and low B-vitamin status.
AB  - Venous thromboembolism (VTE) is a multi-factorial disease involving numerous
      genetic and environmental risk factors. In this study we investigated the
      occurrence and the risk associated with factor V Leiden, hyperhomocysteinemia and
      low folate and vitamin B12 levels in young patients with thrombosis. We studied
      78 patients (33 females/45 males, mean age 33 years) with a history of thrombosis
      in a lower limb. Additionally, 98 healthy subjects (45 females/54 males, mean age
      44 years) were included. Serum levels of homocysteine (Hcy), folate and vitamin
      B12 were assayed. Factor V Leiden and methylenetetrahydrofolate reductase (MTHFR)
      C677T mutations were investigated in all subjects. Factor V Leiden was highly
      prevalent in the patients (39% heterozygous, 10% homozygous vs. 6.3% heterozygous
      in controls). An increase in the risk of idiopathic VTE was associated with Hcy
      levels > 15.2 micromol/l (odds ratio, OR = 2.83), folate < 15.1 nmol/l (OR =
      7.49) and vitamin B12 < 182 pmol/l (OR = 11.97). Low levels of folate or vitamin
      B12 were independently and strongly associated with the risk of VTE in a
      multivariate model (OR for idiopathic thrombosis = 16.44 and 10.76,
      respectively). Twenty patients (53%), carriers of factor V Leiden, had low levels
      of vitamin B12, compared to 28% of patients who were non-carriers of the mutation
      (p = 0.03). In contrast, none of the control carriers of the mutation had a low
      level of vitamin B12. The risk of VTE associated with lower levels of vitamin B12
      and folate was stronger than that introduced by elevated Hcy levels. The
      increased risk of VTE, accompanied by factor V Leiden, may be related to
      confounding environmental factors.

PMID- 14580167
TI  - Analytical evaluation of an automated immunoassay for cardiac troponin I: the
      Vidas Troponin I assay.
AB  - Cardiac troponin I (cTnI) is a sensitive and specific biochemical marker of
      myocardial damage. We assessed the analytical performance of the Vidas Troponin I
      assay (Biomerieux). Controls and serum pools were used to determine the
      precision, analytical sensitivity and linearity; 97.5 and 99.5 percentiles
      concentrations were determined from the reference population. Fifty corresponding
      samples of serum and plasma (lithium-heparin) were tested and the results
      compared. The in vitro stability of serum and plasma samples was assessed at 20
      degrees C, 4 degrees C and -20 degrees C, respectively. Samples of serum were
      used to assess the agreement between the Vidas Troponin I method and the revised
      Dimension RxL cTnI method (Dade-Behring). The total imprecision (CVs) was 13.1
      5.2% for concentrations ranging between 0.25 and 19.8 microg/l cTnI. The lower
      detection limit was <0.1 microg/l. The upper reference limit (97.5 and 99.5
      percentiles) was 0.11 microg/l and 0.12 microg/l, respectively (CV > 10%). The
      assay was linear up to 21 microg/l. The concentrations in lithium-heparin plasma
      were higher compared to those of the matched serum samples. The study of the
      agreement between the Vidas and Dimension RxL cTnI assays showed a total
      concordance of 96% with a bias value of -0.042. The Vidas Troponin I test is a
      fast, precise and sensitive method for the determination of cTnI.

PMID- 14580168
TI  - Can fluoride-oxalate and sodium citrate stabilise homocysteine levels after blood
      collection?
AB  - The concentration of homocysteine (Hcy) rises rapidly after the collection of
      blood. This feature requires blood to be collected into the anticoagulants EDTA
      or heparin and the plasma to then be immediately separated; alternatively, the
      blood may be kept on ice and centrifuged within 1 hour. The use of chemical
      preservatives has been proposed as a means of stabilising Hcy levels in whole
      blood after collection. The objective of this study was to determine whether the
      commonly available fluoride-oxalate (Fl-Ox) and sodium citrate (Na-Cit)
      containers could stabilise Hcy levels in blood. Our results showed that when
      blood was collected into potassium EDTA (K-EDTA) tubes, Hcy levels rose from
      initial levels, on standing at room temperature (approximately 25 degrees C), by
      an average of 21% after 3 hours and 32% after 5 hours. The initial Hcy levels of
      blood collected into Fl-Ox and Na-Cit containers, however, were lower, at
      averages of 89% and 91%, respectively, compared to that of the same samples when
      collected into K-EDTA tubes. Hcy in these samples subsequently rose on standing,
      and after 5 hours was, on the average, 10 and 13% higher, respectively, compared
      with the initial levels in K-EDTA tubes. We conclude that Fl-Ox and Na-Cit do not
      stabilise Hcy in blood after collection and should not be used as preservatives.

PMID- 14580170
TI  - IFCC handbook on Master Program in clinical laboratory sciences.
AB  - This document summarizes the steps in development of a new IFCC Master Program
      and outlines some of the ways the IFCC would assist in setting up such a regional
      Program. This is intended to be of assistance to those who wish to embark on such
      an endeavour.

PMID- 14580169
TI  - Learning curve of a new hospital laboratory. The monitoring of computer-generated
      turnaround time of laboratory tests in an emergency department.
AB  - Learning curves have been described for different health technologies, mainly new
      surgical or diagnostic procedures, but learning curves for a new hospital's
      laboratory procedures have not been systematically studied. To monitor the
      timeliness (turnaround time) of stat tests from the Emergency Department as a
      marker of laboratory quality and to address the issue of a learning curve for
      procedures performed in a new hospital laboratory, we employed a computerized
      system for collecting data of turnaround time (from order entry to result
      verification) on stat tests from the Emergency Department of a newly opened (July
      24, 2000) 471-bed general hospital. The data collection operates without user
      intervention. We evaluated the turnaround times of stat complete blood count and
      biochemistry tests from August 2000 to December 2001. Results show that it took 6
      to 12 months before the turnaround times reached a plateau, we believe that this
      is the learning curve of a new hospital laboratory. Computer-generated turnaround
      times for Emergency Department stat tests appear to be a useful tool for
      monitoring the quality of laboratory tests and can demonstrate the learning curve
      of a new hospital laboratory.

PMID- 14580171
TI  - Winnicott, Balint, and the independent tradition.
AB  - This article compares and contrasts two main aspects of the work of Winnicott and
      Balint: their theories of infantile development and their theoretical and
      clinical work on the use of regression as a therapeutic agent. The relationship
      of their thinking to aspects of the British Independent Group's theories and
      clinical work is noted vis-a-vis the basic acceptance of classical theory and
      technique, acknowledgment and use of some of Klein's contributions, the influence
      of trauma and the external environment on psychic development and
      psychopathology, the importance of holding and the setting, and the reintegration
      of previously split off and lost parts of the self.

PMID- 14580172
TI  - Breaking the solid ground of common sense: undoing "structure" with Michael
      Balint.
AB  - Balint's great merit was to question what, in the classical perspective, was
      assumed as a prerequisite for analysis and thus located beyond analysis: the
      maturity of the ego. A fundamental premise of his work was Ferenczi's distrust
      for the structural model, which praised the maturity of the ego and its verbal,
      social, and adaptive abilities. Ferenczi's view of ego maturation as a trauma
      derivative was strikingly different from the theories of all other psychoanalytic
      schools and seems to be responsible for Balint's understanding of regression as a
      sort of inverted process that enables the undoing of the sheltering structures of
      the mature mind. Balint's understanding of the relation between mature ego and
      regression diverged not only from the ego psychologists, who emphasized the idea
      of therapeutic alliance, but also from most of the authors who embraced the
      object-relational view, like Klein (who considered regression a manifestation of
      the patient's craving for oral gratification), Fairbairn (who gave up the notion
      of regression), and Guntrip (who viewed regression as a schizoid phenomenon
      related to the ego weakness). According to Balint, the clinical appearance of a
      regression would "depend also on the way the regression is recognized, is
      accepted, and is responded to by the analyst." In this respect, his position was
      close to Winnicott's reformulation of the therapeutic action. Yet, the work of
      Balint reflects the persuasion that the progressive fluidification of the solid
      structure could be enabled only by the analyst's capacity for becoming himself or
      herself [unsolid].

PMID- 14580173
TI  - Could Balint have done more for Ferenczi?
AB  - After Ferenczi's death of pernicious anemia in 1933 at the age of 59, Michael
      Balint became the greatest advocate of his late analyst, teacher, colleague, and
      friend. He was faced with widespread avoidance, a conspiracy of silence against
      Ferenczi in the psychoanalytic movement. Ernest Jones, in particular, an
      analysand of Ferenczi and fellow member of the Secret Committee founded by Freud
      before World War I, seriously attacked Ferenczi. In the third volume of the Freud
      biography, Jones alleged that in the last years of his life Ferenczi suffered
      mental deterioration caused by the pernicious anemia, and that this mental
      decline was the real cause of Ferenczi's technical experimentations, thereby
      belittling the importance of Ferenczi's independent work in the last phase of his
      life. This article answers whether Michael Balint, who later became the literary
      executor of Ferenczi, was devoted enough in countering the charges that lead to a
      fifty-year silence on Ferenczi's eminent place in psychoanalysis. Correspondence
      between Balint and Jones is cited, as are reports of Ferenczi's contemporaries;
      Balint's efforts are placed within the context of the psychoanalytic rivalries
      after Freud's death.

PMID- 14580175
TI  - Bibliography of Michael Balint's related works.

PMID- 14580174
TI  - Multilingual bibliography of the works of Michael Balint.

PMID- 14580176
TI  - Autobiographical reflections on writing the biography of Heinz Kohut.

PMID- 14580182
TI  - Determination of cholesterol using o-phthalaldehyde.
AB  - A simple, rapid method for the determination of cholesterol in plasma and tissue
      using o-phthalaldehyde is presented. Comparison of this method with the FeCl(3)
      method gave identical results. However, the o-phthalaldehyde determination is
      three times more sensitive than the FeCl(3) determination (molar extinction
      coefficients of 11,610 and 33,440 for FeCl(3) and o-phthalaldehyde,
      respectively), it takes less time to complete, and the color developed is more
      stable. The o-phthalaldehyde method can be used to assay free and esterified
      cholesterol directly after thin-layer chromatographic separation.

PMID- 14580186
TI  - Simultaneous CD8+ T cell responses to multiple tumor antigen epitopes in a
      multipeptide melanoma vaccine.
AB  - The recent identification and molecular characterization of tumor-associated
      antigens recognized by tumor-reactive CD8+ T lymphocytes has led to the
      development of antigen-specific immunotherapy of cancer. Among other approaches,
      clinical studies have been initiated to assess the in vivo immunogenicity of
      tumor antigen-derived peptides in cancer patients. In this study, we have
      analyzed the CD8+ T cell response of an ocular melanoma patient to a vaccine
      composed of four different tumor antigen-derived peptides administered
      simultaneously in incomplete Freund's adjuvant (IFA). Peptide NY-ESO-1(157-165)
      was remarkably immunogenic and induced a CD8+ T cell response detectable ex vivo
      at an early time point of the vaccination protocol. A CD8+ T cell response to the
      peptide analog Melan-A(26-35 A27L) was also detectable ex vivo at a later time
      point, whereas CD8+ T cells specific for peptide tyrosinase(368-376) were
      detected only after in vitro peptide stimulation. No detectable CD8+ T cell
      response to peptide gp100(457-466) was observed. Vaccine-induced CD8+ T cell
      responses declined rapidly after the initial response but increased again after
      further peptide injections. In addition, tumor antigen-specific CD8+ T cells were
      isolated from a vaccine injection site biopsy sample. Importantly, vaccine
      induced CD8+ T cells specifically lysed tumor cells expressing the corresponding
      antigen. Together, these data demonstrate that simultaneous immunization with
      multiple tumor antigen-derived peptides can result in the elicitation of
      multiepitope-directed CD8+ T cell responses that are reactive against antigen
      expressing tumors and able to infiltrate antigen-containing peripheral sites.

PMID- 14580188
TI  - The kinetics of side chain stabilization during protein folding.
AB  - The rate of stabilization of side chains during protein folding has never been
      carefully studied. Recent developments in labeling proteins with (19)F-labeled
      amino acids coupled with real-time NMR measurements have allowed such
      measurements to be made. This paper describes the application of this method to
      the study of several proteins using 6-(19)F-tryptophan as the reporting group. It
      is found that these side chains adopt their final stable state at the last stages
      of the folding process and that the stabilization of side chains into their final
      conformation is a highly cooperative process. It is also possible to show the
      presence of intermediates in which the side chains are not correctly packed. The
      technique should be applicable to many systems.

PMID- 14580189
TI  - Structural reorganization of the transferrin C-lobe and transferrin receptor upon
      complex formation: the C-lobe binds to the receptor helical domain.
AB  - Human transferrin, a bilobal protein, with each lobe bearing a single iron
      binding site, functions to transport iron into cells. While the N-terminal lobe
      alone does not measurably bind cellular transferrin receptors or serve as an iron
      donor for cells, the C-lobe is capable of both functions. We used hydroxyl
      radical-mediated protein footprinting and mass spectrometry to reveal the
      conformational changes that occur upon complex formation for the human
      transferrin C-lobe (residues 334-679) bound to the ectodomain of human
      transferrin receptor 1 (residues 121-760). Oxidation rates for proteolytic
      peptides in the C-lobe, the receptor, and their complex have been measured by
      mass spectrometry; upon formation of the complex, a dramatic decrease in
      modification rates, indicating protection of specific side chain groups, can be
      seen in C-lobe sequences corresponding to residues 381-401, 415-433, and 457-470.
      Peptide sequences experiencing modification rate decreases in the transferrin
      receptor upon C-lobe binding include residues 232-240, 365-371, 496-508, 580 and
      581, 614-623, 634-646, 647-681, and 733-760. In addition, several peptides in the
      receptor exhibit enhancements in the rate of modification consistent with
      allosteric effects of complex formation. Using tandem mass spectrometry, the
      sites of modification with altered reactivity in the complex include Met382,
      Met389, Trp460, Met464, and Phe427 in the C-lobe and Tyr503, Pro581, Tyr611,
      Leu619, Met635, Phe650, Trp740, Trp754, and Phe760 within the transferrin
      receptor. Using available genetic, biochemical, and structural data, we confirm
      that the conserved RGD sequence (residues 646-648) in the helical domain of the
      transferrin receptor, including residues from Leu619 to Phe650, is a primary
      binding site for the transferrin C-lobe.

PMID- 14580190
TI  - Electrostatic guidance of glycosyl cation migration along the reaction coordinate
      of uracil DNA glycosylase.
AB  - The DNA repair enzyme uracil DNA glycosylase has been crystallized with a
      cationic 1-aza-2'-deoxyribose-containing DNA that mimics the ultimate transition
      state of the reaction in which the water nucleophile attacks the anomeric center
      of the oxacarbenium ion-uracil anion reaction intermediate. Comparison with
      substrate and product structures, and the previous structure of the intermediate
      determined by kinetic isotope effects, reveals an exquisite example of geometric
      strain, least atomic motion, and electrophile migration in biological catalysis.
      This structure provides a rare opportunity to reconstruct the detailed structural
      transformations that occur along an enzymatic reaction coordinate.

PMID- 14580191
TI  - Specific non-native hydrophobic interactions in a hidden folding intermediate:
      implications for protein folding.
AB  - Structures of intermediates and transition states in protein folding are usually
      characterized by amide hydrogen exchange and protein engineering methods and
      interpreted on the basis of the assumption that they have native-like
      conformations. We were able to stabilize and determine the high-resolution
      structure of a partially unfolded intermediate that exists after the rate
      limiting step of a four-helix bundle protein, Rd-apocyt b(562), by
      multidimensional NMR methods. The intermediate has partial native-like secondary
      structure and backbone topology, consistent with our earlier native state
      hydrogen exchange results. However, non-native hydrophobic interactions exist
      throughout the structure. These and other results in the literature suggest that
      non-native hydrophobic interactions may occur generally in partially folded
      states. This can alter the interpretation of mutational protein engineering
      results in terms of native-like side chain interactions. In addition, since the
      intermediate exists after the rate-limiting step and Rd-apocyt b(562) folds very
      rapidly (k(f) approximately 10(4) s(-1)), these results suggest that non-native
      hydrophobic interactions, in the absence of topological misfolding, are repaired
      too rapidly to slow folding and cause the accumulation of folding intermediates.
      More generally, these results illustrate an approach for determining the high
      resolution structure of folding intermediates.

PMID- 14580192
TI  - Effects of maturase binding and Mg2+ concentration on group II intron RNA folding
      investigated by UV cross-linking.
AB  - The Lactococcus lactis Ll.LtrB group II intron encodes a reverse
      transcriptase/maturase (LtrA protein) that promotes RNA splicing by stabilizing
      the catalytically active RNA structure. Here, we mapped 17 UV cross-links induced
      in both wild-type Ll.LtrB RNA and Ll.LtrB-Delta2486 RNA, which has a branch-point
      deletion that prevents splicing, and we used these cross-links to follow tertiary
      structure formation under different conditions in the presence or absence of the
      LtrA protein. Twelve of the cross-links are long-range, with six near known
      tertiary interaction sites in the active RNA structure. In a reaction medium
      containing 0.5 M NH(4)Cl, eight of the 17 cross-links were detected in the
      absence of Mg(2+) or the presence of EDTA, and all were detected at 5 mM Mg(2+),
      where efficient splicing requires the LtrA protein. The frequencies of all but
      four cross-links increased with increasing Mg(2+) concentrations, becoming
      maximal between 4 and 50 mM Mg(2+), where the intron is self-splicing. These
      findings suggest that a high Mg(2+) concentration induces self-splicing by
      globally stabilizing tertiary structure, including key tertiary interactions that
      are required for catalytic activity. Significantly, the binding of the maturase
      under protein-dependent splicing conditions (0.5 M NH(4)Cl and 5 mM Mg(2+))
      increased the frequency of only nine cross-links, seven of which are long-range,
      suggesting that, in contrast to a high Mg(2+) concentration, LtrA promotes
      splicing by stabilizing critical tertiary structure interactions, while leaving
      other regions of the intron relatively flexible. This difference may contribute
      to the high rate of protein-dependent splicing, relative to the rate of self
      splicing. The propensity of the intron RNA to form tertiary structure even at
      relatively low Mg(2+) concentrations raises the possibility that the maturase
      functions at least in part by tertiary structure capture. Finally, an abundant
      central wheel cross-link, present in >50% of the molecules at 5 mM Mg(2+),
      suggests models in which group II intron domains I and II are either coaxially
      stacked or aligned in parallel, bringing the 5'-splice site together with the 3'
      splice site and catalytic core elements at JII/III. This and other cross-links
      provide new constraints for three-dimensional structural modeling of the group II
      intron catalytic core.

PMID- 14580193
TI  - KIX-mediated assembly of the CBP-CREB-HTLV-1 tax coactivator-activator complex.
AB  - The HTLV-1 transcriptional activator Tax is required for viral replication and
      pathogenesis. In concert with human CREB, Tax recruits the human transcriptional
      coactivator and histone acetyltransferase p300/CBP to the HTLV-1 promoter. Here
      we investigate the structural features of the interaction between Tax and the KIX
      domain of p300/CBP. Circular dichroism spectroscopy, nuclear magnetic resonance
      chemical shift perturbation mapping, and sedimentation equilibrium analysis show
      that KIX binds a Tax subdomain corresponding to residues 59-98 of Tax (called
      Tax(59-98)). Circular dichroism spectroscopy suggests that Tax(59-98) is
      intrinsically disordered (natively unfolded) in isolation and adopts an ordered
      conformation upon binding KIX. The interaction is disrupted by a single amino
      acid variation of Tax(59-98) in which leucine 68 is substituted with proline.
      Chemical shift perturbation mapping reveals that the Tax-binding surface of KIX
      is distinct from that utilized by CREB, and corresponds to the site of KIX that
      interacts with the human transcription factors c-Jun and mixed lineage leukemia
      protein (MLL). Sedimentation equilibrium analysis shows that Tax and the
      phosphorylated KID domain of CREB can simultaneously bind KIX to form a ternary
      1:1:1 complex. The results provide a molecular description of the concerted
      recruitment of p300/CBP via the KIX domain by Tax and phosphorylated CREB during
      Tax-mediated gene expression.

PMID- 14580194
TI  - Time-resolved fluorescence allows selective monitoring of Trp30 environmental
      changes in the seven-Trp-containing human pancreatic lipase.
AB  - Human pancreatic lipase (HPL, triacylglycerol acylhydrolase, EC 3.1.1.3) is a
      carboxyl esterase which hydrolyzes insoluble emulsified triglycerides and is
      essential for the efficient digestion of dietary fats. Though the three
      dimensional structure of this enzyme has been determined, monitoring the
      conformational changes that may accompany the binding of various substrates and
      inhibitors is still of interest. Because of its sensitivity and ease of use,
      fluorescence spectroscopy of the intrinsic Trp residues is ideally suited for
      this purpose. However, the presence of seven Trp residues spread all over the HPL
      structure renders the interpretation of the fluorescence changes difficult with
      respect to the identification and location of the conformational or environmental
      changes taking place at the various Trp residues. In this context, the aim of
      this work was to investigate the contribution of the individual Trp residues to
      the fluorescence properties of HPL. To this end, we analyzed the steady-state and
      time-resolved fluorescence parameters of five single-point mutants in which one
      Trp residue was substituted with a weakly fluorescent Phe residue. In addition to
      the Trp residues at positions 30, 86, and 252, strategically located with respect
      to the active site, we also mutated Trp residues at positions 17 and 402, as
      representative residues of the HPL N- and C-terminal domains, respectively. Taken
      together, our data suggested that the solvent-exposed Trp30 residue contributed
      to at least 44% of the overall fluorescence of wild-type HPL. Moreover, we found
      that the long-lived fluorescence lifetime (6.77 ns) of wild-type HPL could be
      specifically attributed to Trp30, a feature that enables selective monitoring of
      its environmental changes. Additionally, Trp residues at positions 17 and 402
      strongly contributed to the 1.61 ns lifetime of HPL, while Trp residues at
      positions 86 and 252 contributed to the 0.29 ns lifetime.

PMID- 14580195
TI  - Structural characterization of EMS16, an antagonist of collagen receptor
      (GPIa/IIa) from the venom of Echis multisquamatus.
AB  - Snake venoms contain a number of hemostatically active C-type lectin-like
      proteins (CLPs), which affect the blood coagulation system, endothelial cells,
      and platelets. CLPs have broad similarities in structure and possess distinct
      biological functions. EMS16, a CLP from Echis multisquamatus venom, which is a
      potent and selective inhibitor of the collagen receptor, glycoprotein Ia/IIa
      (integrin alpha2beta1), has been used in the present study to examine structure
      function relationships in venom CLPs by X-ray crystallography. The structure of
      EMS16, determined at a resolution of 1.9 A, revealed a heterodimer involved with
      domain swapping of the central loop as observed in the structures of other CLPs.
      A part of the glycan was observed and identified as N-acetyl-D-glucosamine
      (GlcNAc) in the electron density map at Asn21 of subunit B, an expected
      glycosylation site. EMS16 had a unique, positively charged electrostatic
      potential patch on the concave surface that may qualify as a site for interaction
      with the I-domain of the glycoprotein Ia/IIa.

PMID- 14580196
TI  - NMR solution structure of viscotoxin C1 from Viscum album species Coloratum ohwi:
      toward a structure-function analysis of viscotoxins.
AB  - The high resolution three-dimensional structure of the newly discovered plant
      viscotoxin C1, from the Asiatic Viscum album ssp. Coloratum ohwi, has been
      determined in solution by (1)H NMR spectroscopy at pH 3.6 and 285 K. The
      viscotoxin C1-fold, consisting of a helix-turn-helix motif and a short stretch of
      an antiparralel beta-sheet is very similar to that found for the highly similar
      viscotoxins A2 and A3 and for other related thionins. Different functional
      properties of members of the thionin family are discussed here in light of the
      structural and electrostatic properties. Among the very homologous family of
      alpha- and beta-thionins, known for their antimicrobial activity, the viscotoxin
      subfamily differs from the other members because of its high toxicity against
      tumoral cells. Key residues for the modulation of viscotoxin cytotoxicity have
      been identified on the basis of sequence and structural alignment.

PMID- 14580197
TI  - Binding and orientation of conantokins in PL vesicles and aligned PL multilayers.
AB  - The association of a ligand with its cognate cell surface receptor can be
      facilitated by interactions between the ligand and the lipid phase of the cell
      membrane. With respect to the N-methyl-D-aspartate receptor (NMDAR), we have
      previously established a low affinity, nonreceptor-mediated interaction of the
      peptidic conantokins with synaptic membranes in conjunction with a high affinity
      binding to the NMDARs present therein [Klein, R. C., Prorok, M., and Castellino,
      F. J. (2003) J. Pept. Res. 61, 307-317]. In the current study, several techniques
      including size-exclusion chromatography, circular dichroism, fluorescence, and
      NMR spectroscopies were used to investigate the binding, conformation, and
      orientation of conantokins and their variants to a variety of phospholipid (PL)
      vesicles and multilayers. We have found that conantokins bind to PLs and that the
      effectors Ca(2+) and spermine slightly increase this binding ability. The
      conantokins preserve a high degree of helical conformation when bound to vesicles
      in the presence of Ca(2+). In the absence of Ca(2+), only conantokin-G (con-G)
      manifests an increase in conantokin helicity with increasing vesicle
      concentration. In solution, the conantokins appear to be localized at the
      headgroup of vesicles and do not insert into the hydrophobic core of the bilayer.
      On aligned PL films, the helical axis of the conantokins can either reside normal
      to the membrane surface or partition in a parallel orientation, depending on the
      nature of the conantokins and the PLs used. These orientation preferences may be
      conjoined with the biological activities of the conantokins.

PMID- 14580198
TI  - Distortion of the three-dimensional structure of the vnd/NK-2 homeodomain bound
      to DNA induced by an embryonically lethal A35T point mutation.
AB  - The three-dimensional solution structure obtained by NMR of the A35T mutant
      vnd/NK-2 homeodomain bound to the vnd/NK-2 consensus 16 bp DNA sequence was
      determined. This mutation to threonine from alanine in position 35 in helix II of
      the vnd/NK-2 homeodomain is associated with early embryonic lethality in
      Drosophila melanogaster. Although the unbound mutant protein is not structured,
      in the DNA-bound state it adopts the three-helix fold characteristic of all known
      homeodomains, but with alterations relative to the structure of the wild-type
      analogue. These structural modifications occur, and are accompanied by a 50-fold
      reduction in the DNA binding affinity, even though most of the protein-DNA
      interactions originally seen for the wild-type homeodomain are found likewise in
      the threonine analogue. Alterations include torsional angle changes in the loop
      between helix I and helix II, and in the turn between helix II and helix III, as
      well as in a distortion of the usual antiparallel orientation of helix I with
      respect to helix II. The alteration of the position of leucine 40 in the A35T
      mutant is proposed to explain the observed 1.27 ppm upfield shift of the
      corresponding amide proton resonance relative to the value observed for the wild
      type analogue. A detailed comparison of the structures of the mutant A35T and
      wild-type vnd/NK-2 homeodomains bound to the cognate DNA is presented. The
      consequences of the structural alteration of the DNA-bound A35T mutant vnd/NK-2
      protein may constitute the basis of the observed early embryonic lethality.

PMID- 14580199
TI  - Ligand binding-induced conformational changes in riboflavin kinase: structural
      basis for the ordered mechanism.
AB  - Riboflavin kinase (RFK) is an essential enzyme catalyzing the phosphorylation of
      riboflavin (vitamin B(2)) in the presence of ATP and Mg(2+) to form the active
      cofactor FMN, which can be further converted to FAD. Previously, the crystal
      structures of RFKs from human and Schizosaccharomyces pombe have been determined
      in the apo form and in complex with MgADP. These structures revealed that RFK
      adopts a novel kinase fold and utilizes a unique nucleotide binding site. The
      structures of the flavin-bound RFK obtained by soaking pre-existing crystals were
      also reported. Because of crystal packing restraints, these flavin-bound RFK
      complexes adopt conformations nearly identical with that of corresponding flavin
      free structures. Here we report the structure of human RFK cocrystallized with
      both MgADP and FMN. Drastic conformational changes associated with flavin binding
      are observed primarily at the so-called Flap I and Flap II loop regions. As a
      result, the bound FMN molecule now interacts with the enzyme extensively and is
      well-ordered. Residues from Flap II interact with Flap I and shield the FMN
      molecule from the solvent. The conformational changes in Flap I resulted in a new
      Mg(2+) coordination pattern in which a FMN phosphate oxygen and Asn36 side chain
      carbonyl are directly coordinating to the Mg(2+) ion. The proposed catalytic base
      Glu86 is well-positioned for activation of the O5' hydroxyl group of riboflavin
      for the phosphoryl transfer reaction. The structural data obtained so far on
      human and yeast RFK complexes provide a rationale for the ordered kinetic
      mechanism of RFK.

PMID- 14580200
TI  - Autocatalytically fragmented light chain of botulinum a neurotoxin is
      enzymatically active.
AB  - The zinc-endopeptidase light chain of botulinum A neurotoxin undergoes
      autocatalytic fragmentation that is accelerated by the presence of the metal
      cofactor, zinc [Ahmed, S. A. et al. (2001) J. Protein Chem. 20, 221-231]. We show
      in this paper that >95% fragmented light chain obtained in the absence of added
      zinc retained 100% of its original catalytic activity against a SNAP-25-derived
      synthetic peptide substrate. In the presence of zinc chloride, when >95% of the
      light chain had undergone autocatalytic fragmentation, the preparation retained
      35% of its original catalytic activity. On the other hand, in the presence of
      glycerol, the light chain did not display autocatalysis and retained 100% of the
      original activity. These results suggest that the activity loss by incubation
      with zinc was not a direct consequence of autocatalysis and that the environment
      of the active site was not affected significantly by the fragmentation. The
      optimum pH 4.2-4.6 for autocatalysis was different than that (pH 7.3) for
      intrinsic catalytic activity. Inhibition of autocatalysis at low pH by a
      competitive inhibitor of catalytic activity rules out the presence of a
      contaminating protease but suggests a rate-limiting step of low pH-induced
      conformational change suitable for autocatalysis. Our results of LC concentration
      dependence of the fragmentation reaction indicate that the autocatalysis occurs
      by both intramolecular and intermolecular mechanisms.

PMID- 14580201
TI  - High affinity binding of Hsp90 is triggered by multiple discrete segments of its
      kinase clients.
AB  - The 90 kDa heat shock protein (Hsp90) cooperates with its co-chaperone Cdc37 to
      provide obligatory support to numerous protein kinases involved in the regulation
      of cellular signal transduction pathways. In this report, crystal structures of
      protein kinases were used to guide the dissection of two kinases [the Src-family
      tyrosine kinase, Lck, and the heme-regulated eIF2alpha kinase (HRI)], and the
      association of Hsp90 and Cdc37 with these constructs was assessed. Hsp90
      interacted with both the N-terminal (NL) and C-terminal (CL) lobes of the
      kinases' catalytic domains. In contrast, Cdc37 interacted only with the NL. The
      Hsp90 antagonist molybdate was necessary to stabilize the interactions between
      isolated subdomains and Hsp90 or Cdc37, but the presence of both lobes of the
      kinases' catalytic domain generated a stable salt-resistant chaperone-client
      heterocomplex. The Hsp90 co-chaperones FKBP52 and p23 interacted with the
      catalytic domain and the NL of Lck, whereas protein phosphatase 5 demonstrated
      unique modes of kinase binding. Cyp40 was a salt labile component of Hsp90
      complexes formed with the full-length, catalytic domains, and N-terminal
      catalytic lobes of Lck and HRI. Additionally, dissections identify a specific
      kinase motif that triggers Hsp90's conformational switching to a high-affinity
      client binding state. Results indicate that the Hsp90 machine acts as a versatile
      chaperone that recognizes multiple regions of non-native proteins, while Cdc37
      binds to a more specific kinase segment, and that concomitant recognition of
      multiple client segments is communicated to generate or stabilize high-affinity
      chaperone-client heterocomplexes.

PMID- 14580202
TI  - Cysteine-scanning mutagenesis and thiol modification of the Rickettsia prowazekii
      ATP/ADP translocase: evidence that TM VIII faces an aqueous channel.
AB  - The contribution of transmembrane region VIII of the Rickettsia prowazekii
      ATP/ADP translocase to the structure of the water-filled channel through which
      ATP is transported was evaluated from the accessibility of three hydrophilic,
      thiol reactive, methanethiosulfonate reagents to a library of 21 single-cysteine
      substitution mutants expressed in Escherichia coli. A negatively charged reagent
      (MTSES) and two positively charged reagents (MTSET and MTSEA) were used. Mutants
      Q323C and G327C did not tolerate cysteine substitution and were almost completely
      deficient in ATP transport. The remaining mutants exhibited 25-226% of the
      cysteine-less parent's transport activity. Five patterns of inhibition of ATP
      transport by the MTS reagents were observed. (i) ATP transport was not inhibited
      by any of the three MTS reagents in mutants Q321C, F324C, A332C, and L335C and
      only marginally in F333C. (ii) Transport activity of mutants F322C, Q326C, and
      A330C was markedly inhibited by all three reagents. (iii) ATP transport was
      inhibited by MTSEA in only the largest group of mutants (M334C, I336C, G337C,
      S338C, N339C, I340C, and I341C). (iv) Transport activity was inhibited by MTSET
      and MTSEA, whereas high concentrations of MTSES were required to inhibit mutants
      W328C, V329C, and I331C. However, mutant W328C could be inhibited by MTSES in the
      presence of sub-K(m) concentrations of the substrate. (v) ATP transport by mutant
      Y325C was unaffected by MTSEA, but inhibited approximately 50% by MTSET and
      MTSES. Transport of ATP protected mutants (F322C, W328C, V329C, A330C, and I331C)
      from MTS inhibition. Mutants in the half of TM VIII that is closest to the
      cytoplasm were not inhibited well by MTSES or MTSET in either whole cells or
      inside-out vesicles. The results indicate that TM VIII makes a major contribution
      to the structure of the aqueous translocation pathway, that the accessibility to
      impermeant thiol reagents is influenced (blocked or stimulated) by substrate, and
      that there is great variation in accessibility to MTS reagents along the length
      of TM VIII.

PMID- 14580203
TI  - Specific binding of cinnamycin (Ro 09-0198) to phosphatidylethanolamine.
      Comparison between micellar and membrane environments.
AB  - Cinnamycin (Ro 09-0198) is a tetracyclic peptide antibiotic that binds
      specifically to phosphatidylethanolamine (PE). Formation of a complex with
      phosphatidylethanolamine follows a 1:1 stoichiometry. Using high-sensitivity
      isothermal titration calorimetry (ITC), we have measured the thermodynamic
      parameters of complex formation for two different PE environments, namely, PE
      dissolved either in octyl glucoside (OG) micelles or in a 1-palmitoyl-2-oleoyl-sn
      glycero-3-phosphocholine (POPC) bilayer membrane. We have compared diacyl-PE with
      lyso-PE and have varied the carbon chain length from 6 to 18. Binding requires
      both a PE headgroup and at least one fatty acyl chain. The optimum chain length
      for complex formation (n) is eight. Longer chains do not enhance the binding
      affinity; for shorter chains, the interaction is weakened. The cinnamycin-PE
      complex has a binding constant K(0) of approximately 10(7)-10(8) M(-1) in the
      POPC membrane and only approximately 10(6) M(-1) in the octyl glucoside micelle.
      The difference can be attributed to the nonspecific hydrophobic interaction of
      cinnamycin with the lipid membrane. Complex formation is enthalpy-driven in OG
      micelles, whereas enthalpy and entropy make equal contributions in bilayer
      membranes. However, for the optimum chain length (n) of eight, the binding
      reaction is also completely enthalpy-driven for the bilayer membrane.

PMID- 14580204
TI  - Functional dissection of cdc37: characterization of domain structure and amino
      acid residues critical for protein kinase binding.
AB  - Hsp90 and its co-chaperone Cdc37 facilitate the folding and activation of
      numerous protein kinases. In this report, we examine the structure-function
      relationships that regulate the interaction of Cdc37 with Hsp90 and with an Hsp90
      dependent kinase, the heme-regulated eIF2alpha kinase (HRI). Limited proteolysis
      of native and recombinant Cdc37, in conjunction with MALDI-TOF mass spectrometry
      analysis of peptide fragments and peptide microsequencing, indicates that Cdc37
      is comprised of three discrete domains. The N-terminal domain (residues 1-126)
      interacts with client HRI molecules. Cdc37's middle domain (residues 128-282)
      interacts with Hsp90, but does not bind to HRI. The C-terminal domain of Cdc37
      (residues 283-378) does not bind Hsp90 or kinase, and no functions were
      ascribable to this domain. Functional assays did, however, suggest that residues
      S127-G163 of Cdc37 serve as an interdomain switch that modulates the ability of
      Cdc37 to sense Hsp90's conformation and thereby mediate Hsp90's regulation of
      Cdc37's kinase-binding activity. Additionally, scanning alanine mutagenesis
      identified four amino acid residues at the N-terminus of Cdc37 that are critical
      for high-affinity binding of Cdc37 to client HRI molecules. One mutation,
      Cdc37/W7A, also implicated this region as an interpreter of Hsp90's conformation.
      Results illuminate the specific Cdc37 motifs underlying the allosteric
      interactions that regulate binding of Hsp90-Cdc37 to immature kinase molecules.

PMID- 14580205
TI  - Base-pair dynamics in an antiparallel DNA triplex measured by catalyzed imino
      proton exchange monitored via 1H NMR spectroscopy.
AB  - Using (1)H NMR spectroscopy, the base-pair opening dynamics of an antiparallel
      foldback DNA triplex and the corresponding duplex has been characterized via
      catalyzed imino proton exchange. The triplex system was found to be in an
      equilibrium between a duplex and a triplex form. The exchange rate between the
      two forms (i.e., the on/off-rate of the third strand) was measured to be 5 s(-1)
      at 1 degrees C, and the base-pair dynamics of both forms were investigated
      separately. Both Watson-Crick and reverse Hoogsteen base pairs were found to have
      base-pair lifetimes in the order of milliseconds. The stability of the Watson
      Crick base pairs was, however, substantially increased in the presence of the
      third strand. In the DNA triplex, the opening dynamics of the reverse Hoogsteen
      base pairs was significantly faster than the dynamics of the Watson-Crick pairs.
      We were able to conclude that, for both Watson-Crick and reverse Hoogsteen base
      pairs, spontaneous and individual opening from within the closed base triplet is
      the dominating opening pathway.

PMID- 14580206
TI  - Roles of cytoplasmic osmolytes, water, and crowding in the response of
      Escherichia coli to osmotic stress: biophysical basis of osmoprotection by
      glycine betaine.
AB  - To better understand the biophysical basis of osmoprotection by glycine betaine
      (GB) and the roles of cytoplasmic osmolytes, water, and macromolecular crowding
      in the growth of osmotically stressed Escherichia coli, we have determined growth
      rates and amounts of GB, K(+), trehalose, biopolymers, and water in the cytoplasm
      of E. coli K-12 grown over a wide range of high external osmolalities (1.02-2.17
      Osm) in MOPS-buffered minimal medium (MBM) containing 1 mM betaine (MBM+GB). As
      osmolality increases, we observe that the amount of cytoplasmic GB increases, the
      amounts of K(+) (the other major cytoplasmic solute) and of biopolymers remain
      relatively constant, and the growth rate and the amount of cytoplasmic water
      decrease strongly, so concentrations of biopolymers and all solutes increase with
      increasing osmolality. We observe the same correlation between the growth rate
      and the amount of cytoplasmic water for cells grown in MBM+GB as in MBM,
      supporting our proposal that the amount of cytoplasmic water is a primary
      determinant of the growth rate of osmotically stressed cells. We also observe the
      same correlation between cytoplasmic concentrations of biopolymers and K(+) for
      cells grown in MBM and MBM+GB, consistent with our hypothesis of compensation
      between the anticipated large perturbing effects on cytoplasmic protein-DNA
      interactions of increases in cytoplasmic concentrations of K(+) and biopolymers
      (crowding) with increasing osmolality. For growth conditions where the amount of
      cytoplasmic water is relatively large, we find that cytoplasmic osmolality is
      adequately predicted by assuming that contributions of individual solutes to
      osmolality are additive and using in vitro osmotic data on osmolytes and a local
      bulk domain model for cytoplasmic water. At moderate growth osmolalities (up to 1
      Osm), we conclude that GB is an efficient osmoprotectant because it is almost as
      excluded from the biopolymer surface in the cytoplasm as it is from native
      protein surface in vitro. At very high growth osmolalities where cells contain
      little cytoplasmic water, predicted cytoplasmic osmolalities greatly exceed
      observed osmolalities, and the efficiency of GB as an osmolality booster
      decreases as the amount of cytoplasmic water decreases.

PMID- 14580207
TI  - Evidence in Escherichia coli that N3-methyladenine lesions and cytotoxicity
      induced by a minor groove binding methyl sulfonate ester can be modulated in vivo
      by netropsin.
AB  - The use of DNA equilibrium binding molecules to transfer alkyl groups to specific
      positions on DNA is an approach to generating cytotoxic DNA damage while avoiding
      the formation of promutagenic lesions that increase the risk for the development
      of secondary cancer. We have previously reported that in vitro a neutral DNA
      equilibrium binding agent based on an N-methylpyrrolecarboxamide dipeptide (lex)
      and modified with an O-methyl sulfonate ester functionality (Me-lex) selectively
      affords N3-methyladenine lesions in >90% yield relative to the formation of other
      adducts. While in vitro interactions between the lex dipeptide and DNA have been
      thoroughly studied, in vivo interactions are more difficult to elucidate. We
      report herein the relationship between the in vivo formation of N3-methyladenine
      and toxicity in wild-type and base excision repair defective mutant Escherichia
      coli. In addition, it is demonstrated that both N3-methyladenine adduction and
      cytotoxicity can be inhibited in vivo with netropsin, a potent competitive
      inhibitor of binding of lex to DNA. The results show a clear relationship between
      the levels of N3-methyladenine and toxicity in an alkA/tag glycosylase mutant
      that cannot remove the adduct from its genome. For methyl methanesulfonate, which
      does not sequence selectively methylate DNA, a relationship between the formation
      of N3-methyladenine and toxicity is also observed. However, netropsin affects
      neither the level of N3-methyladenine nor the toxicity of methyl methanesulfonate
      in E. coli.

PMID- 14580208
TI  - Characterization of the recombinant extracellular domains of human interleukin-20
      receptors and their complexes with interleukin-19 and interleukin-20.
AB  - The soluble extracellular domains of human interleukin-20 (IL-20) receptors I and
      II (sIL-20R1 and sIL20R2), along with their ligands IL-19 and IL-20, were
      expressed in Drosophila S2 cells and purified to homogeneity. Formation of the
      receptor/receptor and ligand/receptor complexes was studied by size exclusion
      chromatography. Both ligands and soluble receptors were found to be monomeric in
      solution; homo- or heterodimers are not formed even at elevated concentrations.
      Under native conditions, both IL-19 and IL-20 form stable ternary 1:1:1 complexes
      with the sIL-20R1 and sIL20R2 receptors, as well as high-affinity binary
      complexes with sIL-20R2. Unexpectedly, sIL-20R1 does not bind on its own to
      either IL-19 or IL-20. Thus, one of the possible consecutive mechanisms of
      formation of the signaling ternary complex may involve two steps: first, the
      ligand binds to receptor II, creating a high-affinity binding site for the
      receptor I, and only then does receptor I complete the complex.

PMID- 14580209
TI  - Syndecan binding sites in the laminin alpha1 chain G domain.
AB  - The laminin alpha1 chain G domain has multiple biological activities. Previously,
      we identified cell binding sequences in the laminin alpha1 chain G domain by
      screening 113 synthetic peptide-polystyrene beads for cell attachment activity.
      Here, we have used a recombinant protein of the laminin alpha1 G domain (rec
      alpha1G) and a large set of synthetic peptides to further identify and
      characterize heparin, cell, and syndecan-4 binding sites in the laminin alpha1
      chain G domain. The rec-alpha1G protein promoted both cell attachment and heparin
      binding (K(D) = 19 nM). Cell attachment to the rec-alpha1G protein was inhibited
      60% by heparin and 30% by EDTA. The heparin binding sites were identified by
      competing heparin binding to the rec-alpha1G protein with 110 synthetic peptides
      in solution. Only two peptides, AG73 (IC(50) = 147 microM) and AG75 (IC(50) = 206
      microM), inhibited heparin binding to rec-alpha1G. When the peptides were
      compared in a solid-phase heparin binding assay, AG73 showed more heparin binding
      than AG75. AG73 also inhibited fibroblast attachment to the rec-alpha1G protein,
      but AG75 did not. Cell attachment to the peptides was studied using peptide
      coated plates and peptide-conjugated sepharose beads. AG73 promoted cell
      attachment in both assays, but AG75 only showed cell attachment activity in the
      bead assay. Additionally, AG73, but not AG75, inhibited branching morphogenesis
      of mouse submandibular glands in organ culture. Furthermore, the rec-alpha1G
      protein bound syndecan-4, and both AG73 and AG75 inhibited this binding. These
      results suggest that the AG73 and AG75 sites are important for heparin and
      syndecan-4 binding in the laminin alpha1 chain G domain. These sites may play a
      critical role in the diverse biological activities involving heparin and syndecan
      4 binding.

PMID- 14580210
TI  - DNA-binding and oligomerization studies of the manganese(II) metalloregulatory
      protein MntR from Bacillus subtilis.
AB  - The metalloregulatory protein MntR from Bacillus subtilis acts as a
      transcriptional regulator of manganese homeostasis. MntR is a member of a
      subfamily of DtxR-related proteins that perform analogous regulatory functions in
      a variety of pathogenic organisms. Metal ions activate MntR to bind DNA and
      repress the transcription of the mntH gene, which encodes for a proton-coupled
      metal ion transporter. Size-exclusion chromatography and sedimentation
      equilibrium ultracentrifugation studies show that apo MntR is predominantly a
      homodimer in solution. Using fluorescence anisotropy measurements, the DNA
      binding properties of MntR have been examined. In the strict absence of divalent
      transition metal ions MntR has a low affinity for the mntH control sequence (K(d)
      > 8.0 microM). However, binding of MntR is stimulated by the presence of Mn(2+)
      and Cd(2+) to generate high affinity binding with K(d) values of 16.0 and 7.3 nM,
      respectively. MntR is also shown to bind the mntH control sequence in the
      presence of other divalent transition metals, including Ni(2+), Cu(2+), and
      Zn(2+), but with much lower affinity (K(d) approximately 1.3-2.3 microM). The
      data here demonstrate that differences in metal-activated DNA binding plays a
      role in the mechanism of manganese(II)-selective transcription factors and that
      the oligomerization of MntR is metal-independent, which distinguishes this
      protein from iron(II)-responsive homologues in the DtxR protein family.

PMID- 14580211
TI  - Investigation of restriction enzyme cofactor requirements: a relationship between
      metal ion properties and sequence specificity.
AB  - Restriction enzymes are important model systems for understanding the mechanistic
      contributions of metal ions to nuclease activity. These systems are unique in
      that they combine distinct functions which have been shown to depend on metal
      ions: high-affinity DNA binding, sequence-specific recognition of DNA, and Mg(II)
      dependent phosphodiester cleavage. While Ca(II) and Mn(II) are commonly used to
      promote DNA binding and cleavage, respectively, the metal ion properties that are
      critical to the support of these functions are not clear. To address this
      question, we assessed the abilities of a series of metal ions to promote DNA
      binding, sequence specificity, and cleavage in the representative PvuII
      endonuclease. Among the metal ions tested [Ca(II), Sr(II), Ba(II), Eu(III),
      Tb(III), Cd(II), Mn(II), Co(II), and Zn(II)], only Mn(II) and Co(II) were similar
      enough to Mg(II) to support detectable cleavage activity. Interestingly, cofactor
      requirements for the support of DNA binding are much more permissive; the survey
      of DNA binding cofactors indicated that Cd(II) and the heavier and larger
      alkaline earth metal ions Sr(II) and Ba(II) were effective cofactors, stimulating
      DNA binding affinity 20-200-fold. Impressively, the trivalent lanthanides Tb(III)
      and Eu(III) promoted DNA binding as efficiently as Ca(II), corresponding to an
      increase in affinity over 1000-fold higher than that observed under metal-free
      conditions. The trend for DNA binding affinity supported by these ions suggests
      that ionic radius and charge are not critical to the promotion of DNA binding. To
      examine the role of metal ions in sequence discrimination, we determined
      specificity factors [K(a)(specific)/K(a)(nonspecific)] in the presence of Cd(II),
      Ba(II), and Tb(III). Most interestingly, all of these ions compromised sequence
      specificity to some degree compared to Ca(II), by either increased affinity for a
      noncognate sequence, decreased affinity for the cognate sequence, or both. These
      results suggest that while amino acid-base contacts are important for
      specificity, the properties of metal ion cofactors at the catalytic site are also
      critical for sequence discrimination. This insight is invaluable to our efforts
      to understand and subsequently design sequence-specific nucleases.

PMID- 14580212
TI  - Effects of DNA adduct structure and sequence context on strand opening of repair
      intermediates and incision by UvrABC nuclease.
AB  - DNA damage recognition of nucleotide excision repair (NER) in Escherichia coli is
      achieved by at least two steps. In the first step, a helical distortion is
      recognized, which leads to a strand opening at the lesion site. The second step
      involves the recognition of the type of chemical modification in the single
      stranded region of DNA during the processing of the lesions by UvrABC. In the
      current work, by comparing the efficiencies of UvrABC incision of several types
      of different DNA adducts, we show that the size and position of the strand
      opening are dependent on the type of DNA adducts. Optimal incision efficiency for
      the C8-guanine adducts of 2-aminofluorene (AF) and N-acetyl-2-aminofluorene (AAF)
      was observed in a bubble of three mismatched nucleotides, whereas the same for C8
      guanine adduct of 1-nitropyrene and N(2)-guanine adducts of benzo[a]pyrene diol
      epoxide (BPDE) was noted in a bubble of six mismatched nucleotides. This suggests
      that the size of the aromatic ring system of the adduct might influence the
      extent and number of bases associated with the opened strand region catalyzed by
      UvrABC. We also showed that the incision efficiency of the AF or AAF adduct was
      affected by the neighboring DNA sequence context, which, in turn, was the result
      of differential binding of UvrA to the substrates. The sequence context effect on
      both incision and binding disappeared when a bubble structure of three bases was
      introduced at the adduct site. We therefore propose that these effects relate to
      the initial step of damage recognition of DNA structural distortion. The
      structure-function relationships in the recognition of the DNA lesions, based on
      our results, have been discussed.

PMID- 14580213
TI  - A C-terminal PDZ motif in NHE3 binds NHERF-1 and enhances cAMP inhibition of
      sodium-hydrogen exchange.
AB  - NHERF-1, a protein adapter containing two tandem PDZ domains, was first
      identified as an essential cofactor required for the phosphorylation and
      downregulation of NHE3 activity in response to elevated intracellular cAMP. NHERF
      1 contains multiple protein interaction domains, but the mechanism by which it
      binds NHE3 remains unknown. Yeast two-hybrid analyses demonstrated that the C
      terminal sequence, STHM, of NHE3 constitutes a PDZ motif critical for its
      association with NHERF-1. In this assay, NHE3 bound both PDZ-I and PDZ-II when
      presented as isolated domains, but mutations of the individual PDZ domains in the
      full-length NHERF-1 suggested a significant preference of NHE3 for the PDZ-II
      domain. To investigate NHERF-1/NHE3 association in cells, NHERF-1 complexes were
      isolated from PS120 cells expressing hexahistidine-tagged NHERF-1 and NHE3 using
      nickel-NTA-agarose. In these experiments, mutating the C-terminal PDZ motif still
      allowed NHE3 binding to NHERF-1, suggesting the presence of additional mechanisms
      or components that stabilized a cellular NHE3/NHERF-1 complex. Transport assays
      in PS120 cells, however, showed that the C-terminal PDZ motif in NHE3 and a
      functional PDZ-II domain in NHERF-1 were required for maximal inhibition of
      sodium-hydrogen exchange in response to forskolin and 8-Br-cAMP. Together, the
      data suggested that the PDZ interaction between the NHE3 C-terminus and a NHERF-1
      PDZ domain enhanced the regulation of sodium-hydrogen exchange by cAMP-elevating
      hormones.

PMID- 14580215
TI  - Mechanism of substrate inhibition in Escherichia coli phosphofructokinase.
AB  - Phosphofructokinase from Escherichia coli (EcPFK) is a homotetramer with four
      active sites, which bind the substrates fructose-6-phosphate (Fru-6-P) and MgATP.
      In the presence of low concentrations of Fru-6-P, MgATP displays substrate
      inhibition. Previous proposals to explain this substrate inhibition have included
      both kinetic and allosteric mechanisms. We have isolated hybrid tetramers
      containing one wild type subunit and three mutated subunits (1:3). The mutated
      subunits contain mutations that decrease affinity for Fru-6-P (R243E) or MgATP
      (F76A/R77D/R82A) allowing us to systematically simplify the possible allosteric
      interactions between the two substrates. In the absence of a rate equation to
      explain the allosteric effects in a tetramer, the data have been compared to
      simulated data for an allosteric dimer. Since the apparent substrate inhibition
      caused by MgATP binding is not seen in hybrid tetramers with only a single native
      MgATP binding site, the proposed kinetic mechanism is not able to explain this
      phenomenon. The data presented are consistent with an allosteric antagonism
      between MgATP in one active site and Fru-6-P in a second active site.

PMID- 14580214
TI  - Cosolvent-induced aggregation inhibits myosin ATPase activity by stabilizing the
      predominant transition intermediate.
AB  - High concentration of the cosolvent poly(ethylene glycol) (PEG) induces
      reversible aggregation of skeletal myosin subfragment 1 (S1) and inhibition of
      its Mg-ATPase activity [Highsmith et al. (1998) Biophys. J. 74, 1465-1472]. In
      the present work the effect of aggregation on the various steps of the ATPase
      cycle was studied. The isomerization and hydrolysis steps of the cycle were not
      affected by S1 aggregation since the formation of the "trapped"
      S1.MgADP.phosphate analogue complexes, which mimic the prehydrolysis M*ATP and
      posthydrolysis M**ADP.P(i) transition states, proceeded without any hindrance.
      Similar conclusions could be reached from the chemical modification of Lys-83 and
      Cys-707 in the presence of MgATP and MgATPgammaS, which indicated that the most
      populated intermediate of the cycle in solubilized and aggregated S1 is
      M**ADP.P(i). The dissociation of the trapped S1.MgADP.phosphate analogue
      complexes resembling the M**ADP.P(i) state was strongly inhibited by PEG-6000,
      showing that the transition from this intermediate is prevented by the
      aggregation. This step is presumably inhibited because the coupled swinging of
      the lever arm from the closed to the open position is constrained by the close
      packing of aggregated S1.

PMID- 14580216
TI  - Mutagenesis of the conserved active-site tyrosine changes a retaining sialidase
      into an inverting sialidase.
AB  - Mutagenesis of the conserved tyrosine (Y370) of the Micromonospora viridifaciens
      sialidase changes the mechanism of catalysis from retention of anomeric
      configuration to an unprecedented inverting mechanism in which water efficiently
      functions as the nucleophile. Three mutants, Y370A, Y370D, and Y370G, were
      produced recombinantly in Escherichia coli, and all are catalytically active
      against the activated substrate 4-methylumbelliferyl alpha-D-N-acetylneuraminide.
      The Y370D mutant was also shown to catalyze the hydrolysis of natural substrate
      analogues such as 3'-sialyllactose. A comparison of the pH-rate profiles for the
      wild-type and the Y370D mutant sialidase reveals no major differences, although
      with respect to the kinetic term k(cat)/K(m), an ionized form of the aspartate
      370 enzyme is catalytically compromised. For the wild-type enzyme, the value of
      the Bronsted parameter beta(lg) on k(cat) is 0.02 +/- 0.03, while for the Y370D
      mutant sialidase beta(lg) = -0.55 +/- 0.03 for the substrates with bad leaving
      groups. Thus, for the wild-type enzyme, a nonchemical step(s) is rate-limiting,
      but for the tyrosine mutant cleavage of the glycosidic C-O bond is rate
      determining. The Bronsted slopes derived for the kinetic parameter k(cat)/K(m)
      display a similar trend (beta(lg) -0.30 +/- 0.04 and -0.74 +/- 0.04 for the wild
      type and Y370D, respectively). These results reveal that the tyrosine residue
      lowers the activation free energy for cleavage of 6'-sialyllactose, a natural
      substrate analogue, by more than 24.9 kJ mol(-1). Evidence is presented that the
      mutant sialidases operate by a dissociative mechanism, and the wild-type enzyme
      operates by a concerted mechanism.

PMID- 14580217
TI  - Hydroperoxy-10,12-octadecadienoic acid stimulates cytochrome P450 3A protein
      aggregation by a mechanism that is inhibited by substrate.
AB  - We recently demonstrated that microsomes from nicardipine-treated rats will form
      cytochrome P450 3A (CYP3A) aggregates when incubated at 37 degrees C. CYP3A
      substrates inhibited the protein aggregation and subsequent degradation,
      suggesting that this process is important in substrate-mediated stabilization of
      CYP3A. In this paper, we demonstrate that oxidative stress is a key factor in the
      formation of CYP3A aggregates in incubated microsomes and in a reconstituted
      system with purified enzymes. Our data further suggest that the effects of
      oxidative stress are mediated by lipid hydroperoxides, which are efficiently
      metabolized by CYP3A. In the presence of substrate, the CYP3A-mediated lipid
      hydroperoxide metabolism is inhibited along with the associated protein
      aggregation. Therefore, these studies provide a mechanistic model of why CYP3A
      has a relatively short half-life and how substrates stabilize CYP3A.

PMID- 14580218
TI  - Effect of anion binding on the thermal reverse reaction of bathoiodopsin: anion
      stabilizes two forms of iodopsin.
AB  - The thermal reactions of the bathoproduct of the long wavelength sensitive visual
      pigment iodopsin were investigated under various anionic and environmental
      conditions, to get an insight into the mechanism leading to the unusual thermal
      isomerization of the retinal chromophore from the trans to the 11-cis form at
      very low temperatures (-160 degrees C). The all-trans chromophore of the
      bathoiodopsin produced from iodopsin in the presence of chloride thermally
      reverted to the 11-cis form, while in the presence of nitrate it kept its all
      trans configuration upon warming. Different protein environments, either in a
      detergent or in phosphatidylcholine (PC) liposomes, did not change the reaction
      characteristics of the bathoiodopsins under the two anionic conditions. However,
      reaction characteristics of bathoiodopsins produced in the absence of small
      anions were dependent on the environment. The trans-to-cis isomerization occurred
      upon warming of bathoiodopsin in the presence of detergent but not in liposomes.
      Spectral measurements revealed that iodopsin in the absence of small anions is a
      mixture of two spectrally distinct forms that exhibit absorption maxima and
      reaction characteristics similar to those of chloride-bound and nitrate-bound
      iodopsins, respectively. Thus, iodopsin exhibits two conformational states, each
      of which is stabilized by the binding of chloride and nitrate, respectively.

PMID- 14580219
TI  - Kinetic analysis of the 4-methylideneimidazole-5-one-containing tyrosine
      aminomutase in enediyne antitumor antibiotic C-1027 biosynthesis.
AB  - The enediyne antitumor antibiotic C-1027 contains an unusual (S)-3-chloro-4,5
      dihydroxy-beta-phenylalanine moiety, which requires an aminomutase for its
      biosynthesis. Previously, we established that SgcC4 is an aminomutase that
      catalyzes the conversion of L-tyrosine to (S)-beta-tyrosine and employs 4
      methylideneimidazole-5-one (MIO) at its active site [Christenson, S. D., Liu, W.,
      Toney, M. D., and Shen, B. (2003) J. Am. Chem. Soc. 125, 6062-6063]. Here, we
      present a thorough analysis of the properties of SgcC4. L-Tyrosine is the best
      substrate among those tested and most likely serves as the in vivo precursor for
      the (S)-3-chloro-4,5-dihydroxy-beta-phenylalanine moiety. The presence of MIO in
      the active site is supported by several lines of evidence. (1) Addition of ATP or
      divalent metal ions has no effect on its aminomutase activity. (2) SgcC4 has
      optimal activity at pH approximately 8.8, similar to the pH optima of MIO
      dependent ammonia lyases. (3) SgcC4 is strongly inhibited by sodium borohydride
      and potassium cyanide, but preincubation with L-tyrosine or 4-hydroxycinnamate
      largely prevents this inhibition. (4) The difference spectrum between SgcC4 and
      its S153A mutant shows a positive peak at approximately 310 nm, indicative of
      MIO. (5) The S153A mutation lowers k(cat)/K(M) 640-fold. The SgcC4-catalyzed
      conversion of L-tyrosine to (S)-beta-tyrosine proceeds via 4-hydroxycinnamate as
      an intermediate. The latter also acts as a competitive inhibitor with respect to
      L-tyrosine and serves as an alternative substrate for the production of beta
      tyrosine in the presence of an amino source. A full time course for the SgcC4
      catalyzed interconversion between L-tyrosine, beta-tyrosine, and 4
      hydroxycinnamate was measured and analyzed to provide estimates for the rate
      constants in a minimal mechanism. SgcC4 also exhibits a beta-tyrosine racemase
      activity, but alpha-tyrosine racemase activity was not detected.

PMID- 14580221
TI  - Placing the risk of seizures with pediatric vaccines in a clinical context.
AB  - In this review we discuss the relationship between commonly administered
      childhood vaccines such as diphtheria-tetanus-whole cell pertussis (DTP) and
      measles-mumps-rubella (MMR), and the risk of nonfebrile and febrile seizure. We
      summarize data from the Vaccine Safety Datalink Study and other studies that
      suggest that DTP and MMR vaccine are associated with a transiently increased risk
      of febrile seizures, and cause between 5-9 and 25-34 additional extra febrile
      seizures per 100 000 immunized children, respectively. DTP and MMR do not appear
      to increase the risk of nonfebrile seizures. We discuss some methodologic
      challenges in studies of vaccines and seizures. Because there is no adequate
      comparison group that would allow for the study of seizures long after
      vaccination, studies of seizures are limited to acute events shortly following
      vaccination. Additionally, while seizures following vaccination are worrisome to
      parents and physicians alike, observational studies of the neurodevelopmental
      outcomes of these children are particularly problematic. We discuss how such
      studies are confounded by the natural history of predisposition to febrile
      seizures and by the increased diagnostic scrutiny that children with febrile
      seizures might undergo. Nevertheless, current data suggest that children with
      febrile seizures do not experience long-term negative effects.Finally, we discuss
      the creation of new clinics designed specifically to assist physicians in
      managing the vaccination of children with a personal or family history of
      seizures. Data from these clinics suggest that vaccination is safe for children
      with a personal or family history of seizures, but statistical power has been
      limited. We conclude by discussing the introduction of new vaccines, and note
      that, even with widespread use, it will take many years before we can be
      knowledgeable about the risk of rare events with these newly licensed products.

PMID- 14580222
TI  - Neonatal sepsis: epidemiology and management.
AB  - Neonatal sepsis is uncommon (2-4 per 1000 live births in developed countries),
      but the rate increases dramatically in premature newborns and those born to
      mothers with infections or prolonged rupture of the fetal membranes. While
      infections caused by organisms contracted from the mother at birth have decreased
      in the past two decades, there has been an increase in nosocomial infections.
      Today, most infants with sepsis have been hospitalized in neonatal intensive care
      units for weeks or months because of extreme prematurity, or because of a
      congenital malformation or surgical condition. Antimicrobial therapy is usually
      begun prior to the isolation of a pathogen and is based upon knowledge of the
      likely microbes in the particular clinical situation. The number of antimicrobial
      agents that can be safely used in neonates is relatively small, and dose
      administration usually needs to be adjusted based upon birthweight and post
      gestational age. The decision whether to treat with antimicrobials should be made
      with consideration of the history, physical examination, and laboratory data. One
      should also consider the effects of the use of antimicrobials on the flora of the
      care unit. Bacterial resistance in the resident flora of the unit has become a
      major problem where there has been indiscriminate use of broad-spectrum agents.

PMID- 14580223
TI  - Psychiatric comorbidities in children with attention deficit hyperactivity
      disorder: implications for management.
AB  - Attention deficit hyperactivity disorder (ADHD) is frequently comorbid with a
      variety of psychiatric disorders. These include oppositional defiant disorder and
      conduct disorder (CD), as well as affective, anxiety, and tic disorders. ADHD and
      ADHD with comorbid CD appear to be distinct subtypes; children with ADHD/CD are
      at higher risk of antisocial personality and substance abuse as adults.
      Stimulants are often effective treatments for aggressive or antisocial behavior
      in patients with ADHD, but mood stabilizers or atypical antipsychotics may be
      used to treat explosive aggressive outbursts. Response to stimulants is not
      affected by comorbid anxiety, but children with ADHD/anxiety disorder may show
      greater benefit from psychosocial interventions than those with ADHD alone. The
      degree of prevalence of major depressive disorder (MDD) and bipolar disorder
      among children with ADHD is controversial, but a subgroup of severely emotionally
      labile ADHD children who present serious management issues for the clinician
      clearly exists. Antidepressants may be used in conjunction with stimulants to
      treat MDD, while mood stabilizers and atypical antipsychotics are often required
      to treat manic symptoms or aggression. After resolution of the manic episode,
      stimulant treatment of the comorbid ADHD may be safely undertaken. Recent
      research suggests that stimulants can be safely used in children with comorbid
      ADHD and tic disorders, but the addition of anti-tic agents to stimulants is
      often necessary. Clinicians who work with patients with ADHD should be prepared
      to deal with a wide range of emotional and behavioral problems beyond the core
      symptoms of inattention and impulsivity/hyperactivity.

PMID- 14580224
TI  - Postoperative pain control in children: a guide to drug choice.
AB  - Postoperative pain in children can usually be well controlled with a combination
      of analgesics, including acetaminophen (paracetamol), NSAIDs, opioids, and
      local/regional anesthesia. Recent research has shown that the dosage of
      acetaminophen required to provide analgesia is higher than the traditional
      dosages used for the regulation of elevated body temperature. Rectal
      administration of acetaminophen gives a lower and more variable bioavailability
      compared with oral administration. There is growing experience with the use of
      NSAIDs in children and several studies have demonstrated the relatively strong
      analgesic potential of these drugs. Titration of opioids to analgesic effect, and
      the use of nurse- and patient-controlled continuous opioid infusions in children
      have gained widespread use and, with proper education and supervision, are
      considered excellent methods of pain control. Local peripheral and central blocks
      decrease the need for anesthetics during surgery and provide effective
      postoperative pain relief.

PMID- 14580225
TI  - Secondary hyperparathyroidism in children with chronic renal failure:
      pathogenesis and treatment.
AB  - Despite advances in the management of patients with chronic renal failure,
      histologic features associated with secondary hyperparathyroidism remain the
      predominant skeletal findings; however, over the last decade the prevalence of
      adynamic bone has increased in both adult and pediatric patients with chronic
      renal failure. The management of children with secondary hyperparathyroidism and
      mild to moderate chronic renal failure should be started early, and should
      include correction of hypocalcemia and metabolic acidosis, maintenance of age
      appropriate serum phosphorus levels, and institution of vitamin D therapy when
      serum intact parathyroid hormone (PTH) measurements are elevated to maintain the
      blood levels within normal limits; however, in children undergoing chronic
      dialysis therapy, the current recommendation is to maintain the serum intact PTH
      levels at least 2-4 times the upper limits of normal to prevent the development
      of low bone turnover disease. Serum calcium, phosphorus, alkaline phosphatase,
      and PTH levels should be monitored frequently, especially in infants and very
      young children. Discontinuation or reduction of vitamin D should be considered
      when there is a rapid decline in PTH levels, persistent elevation in serum
      calcium and serum phosphorus levels, and a significant diminution in alkaline
      phosphatase levels. In addition, a reduction in the calcium concentration of the
      dialysis fluid, and judicious use of calcium-containing salts as phosphate
      binding agents should also be performed in these patients. Although not yet
      extensively used in pediatric patients with secondary hyperparathyroidism,
      several therapeutic alternatives, such as the less calcemic vitamin D analogs,
      including paricalcitol [19-nor-1,25-(OH)(2)D(2)] and doxercalciferol [1-alpha
      (OH)(2)D(2)], calcimimetics, and the availability of a calcium-free, aluminum
      free phosphate binder such as sevelamer hydrochloride and lanthanum carbonate,
      may play significant roles in the future management of children with secondary
      hyperparathyroidism to promote linear growth, prevent parathyroid gland
      hyperplasia, avoid calciphylaxis and, in the long run, avert vascular
      calcifications.

PMID- 14580226
TI  - Safety of sublingual immunotherapy in children with asthma.
AB  - INTRODUCTION: Two previously published studies on sublingual immunotherapy (SLIT)
      did not report any serious adverse event associated with the local therapy;
      however, adverse events were observed in greatly variable percentages. The aim of
      the study was to evaluate the tolerability profile of sublingual swallow and spit
      immunotherapy in a large number of children treated for allergic asthma. METHODS:
      Adverse effects related to sublingual administration of allergen vaccines were
      evaluated in 354 children with allergic asthma. Each patient was followed for at
      least 37 months and received a monthly dose of major allergens (extract) in the
      range of 1.5-14.8mug, equivalent to 3-20 times the amount contained in the usual
      monthly maintenance injections via the subcutaneous routes. RESULTS: No adverse
      event was observed in 90.4% of the children. We observed 0.155 mild to moderate
      reactions per 1000 administrations. Dosage adjustment was required in 15
      patients. In five children, immunotherapy was stopped as a precaution - one
      patient developed rhino-conjunctivitis, two patients developed urticaria, and two
      children developed wheezing. None of the reactions were due to dosage errors. No
      anaphylactic reaction or multiple-organ life-threatening events occurred.
      CONCLUSIONS: The results of our study showed an incidence of mild to moderate
      unwanted effects of 9.6%, lower than that previously reported, and no life
      threatening adverse effects. Nevertheless, asthma, urticaria, and
      rhinoconjunctivitis can occur. SLIT is quite a safe therapy for the treatment of
      allergic children with asthma; however, careful evaluation of the single patient
      is necessary since SLIT is self-administered and a cumulative monthly dose higher
      than that normally administered as an injection is usually attainable.

PMID- 14580227
TI  - Investigation into a possible association between oral lichen planus, the human
      herpesviruses, and the human papillomaviruses.
AB  - BACKGROUND: Oral lichen planus (OLP) is a chronic relapsing cell-mediated
      condition of unknown etiology. The purpose of this study was to ascertain if the
      human herpesviruses (HHVs) or human papillomaviruses (HPVs) act as possible
      factors or co-factors in the pathogenesis of OLP. METHODS: Thirty-eight
      histologically confirmed OLP and 20 normal control buccal mucosa tissue samples
      were analyzed. Polymerase chain reaction analysis was employed to detect members
      of the HHV and HPV families. RESULTS: The Epstein-Barr virus and HHV-7 were
      detected in a small percentage of tissue samples. However, HPV-16 was detected in
      26.3% of OLP samples and 0% of the normal control tissues. The epidermodysplasia
      verruciformis-related HPV types were detected in 42% of OLP samples and 45% of
      normal control samples. CONCLUSION: The results of this study do not suggest a
      causative role for members of the HHV family in the pathology of OLP. However, a
      statistical association was found between HPV-16 presence and OLP.

PMID- 14580228
TI  - Renewable standard reference material for the detection of TP53 mutations.
AB  - BACKGROUND: Numerous DNA-based tests are currently in use or under development
      for the detection of mutations associated with disease. Most of the current
      methods use PCR amplification technologies and detection after separation or
      chromatography of the products. We have developed a panel of standard reference
      materials consisting of 12 plasmid clones containing a 2.0 kb region of the TP53
      gene, including exons 5-9. Eleven of these clones contain a single mutation
      within the mutational hot spots of the TP53 gene, the twelfth is wild-type in
      this region of the gene. The mutations are amino acid (aa) 128: C to T; aa 175: G
      to A; aa 237: T to C; aa 245: G to A; aa 248: C to T; aa 248: G to A; aa 249: G
      to T; aa 273: C to T; aa 273: G to A; aa 282: C to T; and aa 328: T to C. These
      standard reference materials (SRMs), created by site-directed mutagenesis of wild
      type TP53 from a human cell line, include the specific mutations most commonly
      found to be associated with cancer. Their use will improve disease detection by
      serving as validation materials to monitor errors in measurement methods,
      including PCR amplification, amplicon separation, and data analysis from
      different technology platforms. METHODS AND RESULTS: The single point mutations
      of the panel were validated by capillary electrophoresis single-strand
      conformational polymorphism analysis, denaturing gradient gel electrophoresis,
      and denaturing high-performance liquid chromatography, as well as full sequence
      analysis of both DNA strands of the cloned material. For both heteroduplex
      analysis methods, the presence of the mutations was resolved for each SRM.
      CONCLUSION: The generation of a standard TP53 reference panel and demonstration
      that the panel can successfully validate mutation detection across different
      mutation scanning technology platforms. Hence, this panel functions as an SRM to
      normalize results obtained from different laboratories using different
      techniques.

PMID- 14580229
TI  - C677T single nucleotide polymorphisms of the human methylene tetrahydrofolate
      reductase and specific identification : a novel strategy using two-color cross
      correlation fluorescence spectroscopy.
AB  - BACKGROUND: A methylene tetrahydrofolate reductase (MTHFR) deficiency at site
      C677T renders the enzyme thermolabile and consequently represents a risk factor
      for vascular disease, neural tube defects, preeclampsia, and thrombosis. Highly
      specific identification techniques for genotyping are mandatory to give guidance
      for the diagnosis and monitoring of this deficiency. METHODS: A new approach for
      performing genotyping has been introduced with the identification of single
      nucleotide polymorphisms of the human MTHFR. It is based on PCR followed by two
      color cross-correlation fluorescence spectroscopy (FCS). Experiments were carried
      out with green- and red-tagged allele-specific primers, which were fully
      compatible with the two-color fluorescence cross-correlation setup at 488 nm and
      633 nm excitation wavelengths. RESULTS: The measured data of the amplification
      mixes (tubes) were normalized as the maximum correlation amplitude of each tube.
      Correlated and uncorrelated data were optically separated in the amplification
      mixes by their characteristic correlation times, which significantly differed
      from each other. The correlated data were generated in the presence of the proper
      mutated genotype template, whereas uncorrelated data were due to the absence of
      the proper genotype template. Furthermore, the specific association of the two
      color fluorescence correlated signals with the target DNA was experimentally
      proven. Using this novel two-color cross-correlation approach, the MTHFR
      genotypes, which were determined in 21 clinical samples, showed concordance with
      methods involving a PCR-based assay with hexachloro-6-carboxy-fluorescein (HEX)-
      and 6-carboxy-fluorescein (FAM)-tagged allele-specific primers and a subsequent
      separation step with capillary electrophoresis, yet are simpler to perform. There
      was no evidence of a central trend of false-positive or false-negative results.
      We demonstrated how the novel, ultrasensitive typing system could be applied to
      studies where researchers are trying to perfect their assays and are often
      working with the unknown, or application to problematic assays in a clinical
      environment for those involved in molecular diagnosis. CONCLUSIONS: We present an
      alternative method to those commonly used in genotyping. Two-color cross
      correlation FCS allows the detection of the fluorescence signals specifically
      associated with the heterozygous mutated, the homozygous mutated, and normal
      individuals, as exemplified in this study. The presence of nonspecific
      amplification products, which interfere with subsequent DNA analysis, could
      therefore highlight the need for two-color cross-correlation FCS as a means of
      discriminating between specific association of the fluorescence signals with the
      target DNA and DNA not related to the target.

PMID- 14580230
TI  - Uniparental disomy and Robertsonian translocations: risk estimation and prenatal
      testing.
AB  - BACKGROUND: Uniparental disomy (UPD) is defined by the inheritance of both
      homologous chromosomes from only one parent, resulting in an imbalance of the
      expression of imprinted genes. With the recent identification of several diseases
      associated with UPD, the diagnostic significance of this molecular finding is a
      focus of interest. Acrocentric chromosomes involved in Robertsonian
      translocations (RTs) are particularly prone to being affected by mis-segregation
      events, possibly resulting in UPD. While UPDs of chromosomes 13, 21, and 22 have
      no clinical consequences, and therefore have no diagnostic impact despite of
      homozygosity of recessive alleles, prenatal testing for UPDs 14 or 15 is becoming
      increasingly asked for. METHODS: Thirty-one fetuses with nonhomologous balanced
      RTs involving chromosome 14 were tested for UPD14 by microsatellite typing.
      RESULTS: No cases of maternal UPD14 were detected among the 31 fetuses analyzed.
      CONCLUSIONS: Based on our own data from molecular testing in 31 prenatal RT cases
      and findings in the published literature, we delineated a risk of 0.3% for a UPD
      with clinical consequences for prenatally detected carriers of a nonhomologous
      RT. Prenatal UPD testing is not associated with any additional risk to the
      pregnancy once invasive prenatal testing has been carried out. However, the
      possibly conflicting consequences in the case of a prenatal UPD identification
      should be discussed in advance. Furthermore, risk figures in specific clinical
      cohorts, such as couples prior to intracytoplasmic sperm injection, as well as
      questions of prenatal diagnostic management, will be discussed.

PMID- 14580231
TI  - Endothelial nitric oxide synthase gene intron 4 polymorphism in type 2 diabetes
      mellitus.
AB  - INTRODUCTION: Endothelial nitric oxide synthase (ecNOS) is a key regulator of
      vascular nitric oxide production. Polymorphism in intron 4 of the ecNOS gene is
      implicated in cardiovascular and renal diseases. We investigated a potential
      involvement of this polymorphism in the development of type 2 diabetes mellitus
      and its renal complications. METHODS: This preliminary study involved 410
      individuals with type 2 diabetes and 330 healthy control subjects. From the
      diabetes group 178 patients had diabetic nephropathy. All subjects were genotyped
      for the ecNOS4 polymorphism by the polymerase chain reaction (PCR) followed by
      gel electrophoresis. Genotype and allele frequencies were compared between
      diabetes patients with and without nephropathy and the control group. All
      calculations were performed using the Statistical Package for the Social Sciences
      (SPSS, Inc., Chicago, IL, USA) for Windows 5.0. The chi-square test and Fisher's
      exact test were used for case-control comparisons. The Kruskal-Wallis test was
      used for the comparison of subgroups of patients with diabetes. RESULTS: The
      analysis revealed that patients with diabetes, regardless of their nephropathy
      status, were significantly different in genotype distribution and 4a allele
      frequencies compared with controls (p < 0.05). The frequency of aa genotype was
      8.2% in diabetic patients without nephropathy, 8.4% with those with nephropathy
      and 1.2% in controls. The 4a allele showed a significant effect on diabetic
      nephropathy, with odds ratio of 2.24 (95% confidence interval 1.12-3.40). There
      were no significant differences in the 4a allele frequency between the
      normotensive and hypertensive patients with diabetes. CONCLUSION: Our results
      suggest that the ecNOS gene polymorphism can serve as a useful genetic marker of
      increased susceptibility to type 2 diabetes and its renal complications.

PMID- 14580232
TI  - Hyperekplexia (startle disease): a novel mutation (S270T) in the M2 domain of the
      GLRA1 gene and a molecular review of the disorder.
AB  - BACKGROUND: We report on a novel mutation (S270T) in the M2 domain of the GLRA1
      (alpha subunit of the glycine receptor) gene causing autosomal dominant
      hyperekplexia in a neonate, the mother and maternal uncle. All affected members
      showed the typical clinical features of the disorder. This novel S270T (T1188A)
      mutation is located in the boundary of the transmembrane M2 domain of the GLRA1
      protein, close to other previously reported mutations. Mutations in this 'hot
      spot' domain of GLRA1 are frequent in autosomal dominant hyperekplexia but are
      not usually seen in the autosomal recessive form of the disease in which both the
      M1 and the carboxy terminal domains have been implicated. METHODS: Genomic DNA
      was extracted by standard procedures from peripheral blood leukocytes and exon 6
      of the GLRA1 gene was amplified using primers and PCR conditions. A complete
      sequence analysis of the fragment was performed. DNA sequences were analyzed both
      by direct observation of the electropherogram and by comparison with the
      published sequence. RESULTS: The proband had metabolic acidosis, which was
      probably related to continuous contractions of somatic muscles and intractable
      hypertonia. Data seem to show a direct relationship between the mechanism of
      inheritance of the disorder and the location of the molecular defect. The
      patients showed almost all the clinical signs of hyperekplexia: exaggerated
      startle response, muscle hypertonia in response to unexpected tactile and/or
      auditory stimuli, hyperexcitability, and sudden falls.

PMID- 14580233
TI  - A novel mutation in exon 5 of the glucokinase gene in an Argentinian family with
      maturity onset diabetes of the young.
AB  - Maturity onset diabetes of the young (MODY) is caused by mutations in at least
      six different genes, including the glucokinase gene (MODY 2) and genes encoding
      the tissue-specific transcription factors (MODY 1 and MODY 3-6). To determine the
      presence of mutations in MODY 2 in four members of a family who have the clinical
      characteristics of MODY, we performed polymerase chain reaction and single strand
      conformation polymorphism screening, followed by DNA sequencing. We found a novel
      mutation which consisted of the deletion of a cytosine in the position 2 of the
      exon 5 codon 168. This mutation produced a frame shift which determines a stop
      codon at position 203 in exon 6. The identification of a mutation in glucokinase
      gene and transcription factor genes in patients with early-onset diabetes
      confirms the diagnosis of MODY and has important implications for clinical
      management.

PMID- 14580234
TI  - Expression and localization of tumour necrosis factor-alpha and its converting
      enzyme in human abdominal aortic aneurysm.
AB  - Abdominal aortic aneurysm (AAA) is characterized by chronic aortic wall
      inflammation and loss of matrix components. Proinflammatory cytokines such as
      tumour necrosis factor-alpha (TNF-alpha) are thought to be involved in this
      inflammatory process and, therefore, to play an important role in the
      pathogenesis of human AAA. TNF-alpha-converting enzyme (TACE) has recently been
      purified and cloned as a disintegrin and metalloproteinase that converts TNF
      alpha precursor into its mature form. The aim of the present study was to
      determine whether TNF-alpha and TACE were expressed and localized in aortic
      tissues in human AAA. Infrarenal aortic tissues were obtained from AAA patients
      (n=19) undergoing elective aneurysm reconstruction and from autopsy cases without
      cardiovascular disorders as normal controls (n=5). Internal thoracic artery
      samples were also obtained from patients with coronary artery disease undergoing
      coronary artery bypass grafting to represent biopsied conduit vessels (n=5). The
      AAA specimens were taken from the mid-portion of the aneurysm and from the
      longitudinal transition zone between the non-dilated aorta and the proximal
      aspect of the aneurysm. TNF-alpha and TACE mRNA levels were determined by real
      time quantitative reverse transcriptase-PCR. Expression levels of both TNF-alpha
      mRNA and TACE mRNA were significantly greater in the transition zone than in the
      mid-portion (both P<0.05). Expression levels of both forms of mRNA were
      significantly higher in AAA samples than in control aortas or atherosclerotic
      arteries. There was a significant correlation between the expression of TNF-alpha
      mRNA with that of TACE mRNA in AAA (r=0.54, P<0.005). Immunostaining was positive
      for both TNF-alpha and TACE in CD68-positive macrophages in the media and
      adventitia obtained from the transition zone in AAA, whereas neither TNF-alpha
      nor TACE was expressed in control vessels. In conclusion, the concomitant
      activation and localization of TNF-alpha and TACE in the media and adventitia of
      the transition zone in human AAA underlines the importance of this system in the
      pathogenesis of this disorder.

PMID- 14580236
TI  - Dihydrodipicolinate synthase is not inhibited by its substrate, (S)-aspartate
      beta-semialdehyde.
AB  - DHDPS (dihydrodipicolinate synthase; EC 4.2.1.52) is the enzyme that catalyses
      the first unique step of lysine biosynthesis in plants and micro-organisms. As
      such, it has attracted much attention as a target for herbicide and anti
      microbial action. DHDPS has two substrates: pyruvate and ( S )-aspartate beta
      semialdehyde [( S )-ASA]. There are various literature reports that suggest that
      high levels of ( S )-ASA inhibit the enzyme [Karsten (1997) Biochemistry 36, 1730
      1739; Stahly (1969) Biochim. Biophys. Acta 191, 439-451], whereas others have not
      observed this phenomenon. We have resolved this long-running literature debate
      and shown unequivocally that this difference in reported behaviour can be
      attributed to differences in the preparation of ( S )-ASA used by each
      researcher. DHDPS is not inhibited by its substrate; rather, the inhibition is
      due to an, as yet, unidentified inhibitor in preparations of the substrate
      generated by ozonolysis. Furthermore, we demonstrate that ( R )-ASA is neither an
      inhibitor nor a substrate of DHDPS from Escherichia coli.

PMID- 14580235
TI  - Ras activation in response to lysophosphatidic acid requires a permissive input
      from the epidermal growth factor receptor.
AB  - The topology of the signalling pathway linking the G-protein-coupled receptor
      agonist lysophosphatidic acid (LPA) to extracellular-signal-regulated kinase
      activation remains undeciphered. In the present study, we report that analysis of
      LPA signals at the level of Ras-GTP formation and Ras nucleotide exchange
      discriminates true mediatory signals from permissive activities that do not
      participate in signal relay. Hence, whereas pertussis toxin (PTX) treatment
      impairs stimulation of nucleotide exchange, epidermal growth factor receptor
      (EGFR) inhibition does not compromise LPA-induced acceleration of nucleotide
      exchange, but instead attenuates basal nucleotide turnover on Ras. Our data
      indicate that LPA activation of Ras proceeds via PTX-sensitive G(i/o)-proteins
      and requires a permissive input from basal EGFR activity.

PMID- 14580237
TI  - Molecular mechanisms regulating protein kinase Czeta turnover and cellular
      transformation.
AB  - The regulation of protein kinase C (PKC)zeta in relation to its turnover, cell
      growth and transformation was investigated in Rat2 fibroblasts by over-expressing
      wild-type or mutant forms of PKCzeta. Deletion of the pseudosubstrate site (PSS)
      produced the most active mutant (PKCzeta Delta PSS), but mutants designed to
      mimic phosphorylated PKCzeta had lower specific activities in an in vitro assay.
      The mutant lacking phosphorylation at the Thr-560 site (T560A) had similar
      specific activity to wild-type PKCzeta. The T560A mutant also protected PKCzeta
      against proteolysis, whereas phosphorylation at Thr-410 targeted it towards
      proteosomal degradation. Blocking proteosomal degradation with lactacystin caused
      the accumulation of full-length PKCzeta Delta PSS, T410E, PKCzeta Delta PSS
      T410/560E, PKCzeta and T560A. Expressed PKCzeta activity was paralleled by
      extracellular-regulated protein kinase activation, increased cell division, serum
      independent growth and focus formation. These foci were seen for cells expressing
      higher PKCzeta activity (PKCzeta Delta PSS, PKCzeta Delta PSS T410/560E and T560A
      mutants), but these fibroblasts did not show significant anchorage-independent
      growth. This work provides novel information concerning the role of the PSS and
      phosphorylation sites in regulating the activity and turnover of an atypical PKC
      and shows how this activity can induce cell transformation with respect to focus
      formation.

PMID- 14580241
TI  - Introducing a new section to Breast Cancer Research: endocrinology and hormone
      therapy.
AB  - Endocrine therapy is increasingly understood as the conceptual basis for the
      future treatment and prevention of breast cancer. Endocrine agents have
      considerably changed the approach to targeted treatment during the past two
      decades, and select endocrine agents have advanced the goal of preventing breast
      cancer. Progress has occurred because of a vigorous interaction between
      laboratory scientists and the clinical trials community. Breast Cancer Research
      is launching a new section on endocrinology and hormone therapy in order to
      invigorate this exchange and challenge our readers with novel concepts that might
      result in enhanced survival in breast cancer.

PMID- 14580238
TI  - Characterization of a pseudoachondroplasia-associated mutation (His587-->Arg) in
      the C-terminal, collagen-binding domain of cartilage oligomeric matrix protein
      (COMP).
AB  - We have introduced a pseudoachondroplasia-associated mutation (His(587)-->Arg)
      into the C-terminal collagen-binding domain of COMP (cartilage oligomeric matrix
      protein) and recombinantly expressed the full-length protein as well as truncated
      fragments in HEK-293 cells. CD spectroscopy revealed only subtle differences in
      the overall secondary structure of full-length proteins. Interestingly, the
      mutant COMP did not aggregate in the presence of calcium, as does the wild-type
      protein. The binding site for collagens was recently mapped to amino acids 579
      595 and it was assumed that the His(587)-->Arg mutation influences collagen
      binding. However full-length mutant COMP bound to collagens I, II and IX, and the
      binding was not significantly different from that of wild-type COMP. Also a COMP
      His(587)-->Arg fragment encompassing the calcium-binding repeats and the C
      terminal collagen-binding domain bound collagens equally well as the
      corresponding wild-type protein. The recombinant fragments encompassing the C
      terminal domain alone showed multiple bands following SDS/PAGE, although their
      theoretical molecular masses could be verified by MS. A temperature-induced
      conformational change was observed in CD spectroscopy, and negative-staining
      electron microscopy demonstrated that both wild-type and mutant proteins formed
      defined elongated aggregates after heating to 60 degrees C. Our results suggest
      that the His(587)-->Arg mutation is not itself deleterious to the structure and
      collagen-binding of COMP.

PMID- 14580243
TI  - American Society for Clinical Oncology 39th Annual Meeting, Chicago, Illinois,
      USA, 31 May to 3 June 2003: breast cancer neoadjuvant and adjuvant chemotherapy-
      prognostic and predictive markers.
AB  - The annual American Society of Clinical Oncology congress is the largest forum
      for cancer professionals in the world, promoting new developments in cancer
      medicine. A wide spectrum of subjects relevant to breast cancer research and
      treatment was covered in this year's meeting, including chemotherapy in the
      neoadjuvant and adjuvant settings, molecular and gene profiling studies, and use
      of more conventional prognostic and predictive markers of outcome. This report
      discusses some of the highlights in translational and clinical aspects of early
      breast cancer management presented at the meeting.

PMID- 14580242
TI  - Inflammatory breast cancer: clinical progress and the main problems that must be
      addressed.
AB  - Inflammatory breast cancer is a rare but highly aggressive form of locally
      advanced breast cancer. Historically, this disease was uniformly fatal; however,
      with the advent of induction chemotherapy and carefully coordinated multimodality
      treatment, the prognosis of these patients has improved. This article reviews the
      clinical characteristics of inflammatory breast cancer and the recent advances in
      therapy.

PMID- 14580244
TI  - Should all adjuvant breast cancer patients receive a bisphosphonate?
AB  - This commentary discusses the report by Trevor Powles and colleagues on their
      double-blind, placebo-controlled randomised trial of 2 years' adjuvant oral
      clodronate. Although the reported survival benefit in the clodronate-treated
      group confirms the results of one prior study as well as the generally held view
      that bisphosphonates could be advantageous, the reviewer does not feel that the
      data support the universal use of this additional adjuvant therapy.

PMID- 14580245
TI  - Are herbal remedies and dietary supplements safe and effective for breast cancer
      patients?
AB  - There remains limited scientific evidence on the efficacy and safety of 'natural'
      therapies such as herbal remedies and dietary supplements. Nevertheless, breast
      cancer patients are particularly prone to purchasing such products because of the
      perception that 'natural' products are less toxic than conventional prescribed
      medicines. However, the potential for interactions of supplements with current
      medications, the potential for adverse effects from consumption at high levels,
      and the lack of disclosure of such treatments by the patient to their doctor are
      serious public health issues. Robust clinical trials are required to prove the
      efficacy and lack of adverse effects of such preparations, and communication
      between patients and doctors must be improved and doctors made more aware that
      their patients may be seeking advice and treatment from sources outside
      conventional medicine.

PMID- 14580246
TI  - Microarray technology and its effect on breast cancer (re)classification and
      prediction of outcome.

PMID- 14580247
TI  - The diagnosis and management of pre-invasive breast disease: the role of new
      diagnostic techniques.
AB  - In recent years we have seen significantly increased use of minimally invasive
      diagnostic techniques in the management of breast disease. There is wide
      recognition of fine needle aspiration and core biopsy as the principal diagnostic
      methods. However, concerns exist regarding their reliability. This article
      provides a brief overview of the major diagnostic issues related to use of fine
      needle aspiration, core biopsy and ductal lavage. It summarizes areas of use for
      each technique, outlines the main diagnostic pitfalls and their causes, and
      provides a perspective on future developments in the field.

PMID- 14580248
TI  - The diagnosis and management of pre-invasive breast disease: problems associated
      with management of pre-invasive lesions.
AB  - The treatment of ductal carcinoma in situ (DCIS) involves adequate surgical
      excision with adjuvant radiotherapy where appropriate. An inadequate excision
      margin and young age are independent risk factors for local recurrence. Routine
      surgery to axillary lymph nodes is not recommended in pure DCIS. In localised
      DCIS, adjuvant radiotherapy is recommended on the basis of tumour size, margin
      width and pathological subtypes. The role of adjuvant tamoxifen as systemic
      therapy is controversial. The treatment of atypical ductal/lobular hyperplasia
      and lobular carcinoma in situ involves surgical excision to exclude coexisting
      DCIS or invasive disease.

PMID- 14580249
TI  - The diagnosis and management of pre-invasive breast disease: genetic alterations
      in pre-invasive lesions.
AB  - The development of modern molecular genetic techniques has allowed breast cancer
      researchers to clarify the multistep model of breast carcinogenesis. Laser
      capture microdissection coupled with comparative genomic hybridisation and/or
      loss-of-heterozygosity methods have confirmed that many pre-invasive lesions of
      the breast harbour chromosomal abnormalities at loci known to be altered in
      invasive breast carcinomas. Current data do not provide strong evidence for
      ductal hyperplasia of usual type as a precursor lesion, although some are
      monoclonal proliferations; however, atypical hyperplasia and in situ carcinoma
      appear to be nonobligate precursors. We review current knowledge and the
      contribution of molecular genetics in the understanding of breast cancer
      precursors and pre-invasive lesions.

PMID- 14580250
TI  - The diagnosis and management of pre-invasive breast disease: promise of new
      technologies in understanding pre-invasive breast lesions.
AB  - Array-based comparative genomic hybridization, RNA expression profiling, and
      proteomic analyses are new molecular technologies used to study breast cancer.
      Invasive breast cancers were originally evaluated because they provided ample
      quantities of DNA, RNA, and protein. The application of these technologies to pre
      invasive breast lesions is discussed, including methods that facilitate their
      implementation. Data indicate that atypical ductal hyperplasia and ductal
      carcinoma in situ are precursor lesions molecularly similar to adjacent invasive
      breast cancer. It is expected that molecular technologies will identify breast
      tissue at risk for the development of unfavorable subtypes of invasive breast
      cancer and reveal strategies for targeted chemoprevention or eradication.

PMID- 14580251
TI  - Positron emitting 18F-2-deoxy-2-fluoro-D-glucose: potential hot new therapy.
AB  - Preclinical studies suggest that 18F-2-deoxy-2-fluoro-D-glucose (18F-FDG) kills
      breast cancer cells without significant marrow toxicity or parenchymal toxicity.
      Radiation dose calculations estimated from fluorodeoxyglucose positron emission
      tomography images in women with metastatic disease indicate that 18F-FDG should
      be a feasible and safe option in humans. Because the available radiotherapeutic
      agents, strontium 89 and samarium 153 provide palliation to a limited population
      of women with bony metastases, new radiopharmaceutical agents with broader
      applicability are needed. The development of 18F-FDG as the first positron
      emitting radiotherapeutic has the potential to be an innovative treatment, not
      only in osteoblastic disease, but also in osteolytic disease and in soft tissue
      metastases.

PMID- 14580252
TI  - Health food store recommendations: implications for breast cancer patients.
AB  - BACKGROUND: Many breast cancer patients use complementary and alternative
      medicine (CAM). We aimed to determine what advice health food store employees
      present to individuals seeking treatment options for breast cancer. METHODS:
      Eight data gatherers asked employees of all retail health food stores in a major
      Canadian city, what they recommended for a patient with breast cancer. The data
      gatherers inquired about product safety, potential drug interactions, costs and
      efficacy. They also enquired about employee training related to the products.
      RESULTS: Thirty-four stores were examined. A total of 33 different products were
      recommended, none of which are supported by sufficient evidence of efficacy. The
      average cost of the products they recommended was 58.09 dollars (CAD) (minimum
      5.28 dollars, median 32.99 dollars, maximum 600 dollars) per month. Twenty-three
      employees (68%) did not ask whether the patient took prescription medications.
      Fifteen employees (44%) recommended visiting a healthcare professional
      (naturopaths (9), physicians (5), nutritionists (1). Three employees (8.8%)
      discussed potential adverse effects of the products. Eight employees (23.5%)
      discussed the potential for drug interactions. Two employees (5.9%) suggested a
      possible cure with the products and one employee (2.9%) suggested discontinuing
      Tamoxifen. Four employees (11.8%) recommended lifestyle changes and three
      employees (8.8%) recommended books for further reading on the products.
      CONCLUSION: This study draws attention to the heterogeneity of advice provided by
      natural health food stores to individuals seeking treatments for breast cancer,
      and the safety and cost implications of some of the products recommended.
      Physicians should enquire carefully about the use of natural health food products
      by patients with breast cancer. Regulators need to consider regulations to
      protect vulnerable patients from incurring significant costs in their purchasing
      of natural health food products lacking evidence of benefit and of questionable
      safety.

PMID- 14580254
TI  - Transforming growth factor beta-regulated gene expression in a mouse mammary
      gland epithelial cell line.
AB  - BACKGROUND: Transforming growth factor beta (TGF-beta) plays an essential role in
      a wide array of cellular processes. The most well studied TGF-beta response in
      normal epithelial cells is growth inhibition. In some cell types, TGF-beta
      induces an epithelial to mesenchymal transition (EMT). NMuMG is a nontransformed
      mouse mammary gland epithelial cell line that exhibits both a growth inhibitory
      response and an EMT response to TGF-beta, rendering NMuMG cells a good model
      system for studying these TGF-beta effects. METHOD: A National Institutes of
      Aging mouse 15,000 cDNA microarray was used to profile the gene expression of
      NMuMG cells treated with TGF-beta1 for 1, 6, or 24 hours. Data analyses were
      performed using GenePixPro and GeneSpring software. Selected microarray results
      were verified by northern analyses. RESULTS: Of the 15,000 genes examined by
      microarray, 939 were upregulated or downregulated by TGF-beta. This represents
      approximately 10% of the genes examined, minus redundancy. Seven genes previously
      not known to be regulated by TGF-beta at the transcriptional level (Akt and RhoB)
      or not at all (IQGAP1, mCalpain, actinin alpha3, Ikki, PP2A-PR53), were
      identified and their regulation by TGF-beta verified by northern blotting. Cell
      cycle pathway examination demonstrated downregulation of cyclin D2, c-myc, Id2,
      p107, E2F5, cyclin A, cyclin B, and cyclin H. Examination of cell adhesion
      related genes revealed upregulation of c-Jun, alpha-actinin, actin, myosin light
      chain, p120cas catenin (Catns), alpha-integrin, integrin beta5, fibronectin,
      IQGAP1, and mCalpain. CONCLUSION: Using a cDNA microarray to examine TGF-beta
      regulated gene expression in NMuMG cells, we have shown regulation of multiple
      genes that play important roles in cell cycle control and EMT. In addition, we
      have identified several novel TGF-beta-regulated genes that may mediate
      previously unknown TGF-beta functions.

PMID- 14580253
TI  - Cancer incidence in relatives of a population-based set of cases of early-onset
      breast cancer with a known BRCA1 and BRCA2 mutation status.
AB  - BACKGROUND: Relatives of breast cancer cases have an increased risk of the
      disease. The risk increases with increasing numbers and decreasing age of onset
      of affected relatives. In families with a BRCA1 or a BRCA2 mutation, individual
      carrier status predicts the risk of breast cancer. In relatives of cases where
      both BRCA1 and BRCA2 mutations are excluded, the risk remains undetermined.
      METHODS: Standardized incidence ratios (SIRs) and cumulative cancer incidences
      were calculated for relatives of a population-based set of early-onset breast
      cancer index cases (younger than age 41 years) with a defined BRCA mutation
      status (n = 203). RESULTS: In first-degree relatives (FDRs) of mutation-negative
      cases, breast cancer incidences (SIR = 2.3), prostate cancer incidences (SIR =
      1.7), cervix cancer incidences (SIR = 3.3) and nonmelanoma skin cancer incidences
      (SIR = 2.8) were increased. The risks of breast cancer, prostate cancer and
      nonmelanoma skin cancer were further increased in FDRs of breast cancer cases
      younger than 36 years of age. In high-risk individuals with at least one relative
      with breast cancer apart from the index case, but no BRCA mutation in the family,
      breast cancer incidence was increased (SIR = 5.3); again the prostate cancer
      incidence was elevated (SIR = 2.5). The cumulative incidence of breast cancer at
      ages 50 and 70 years for FDRs of index cases without a BRCA mutation was 3.6% and
      12.8%, respectively. Similarly, the cumulative incidence of breast cancer for
      high-risk women was 6.3% and 21.1% at ages 50 and 70 years, and that for FDRs of
      BRCA mutation carriers was 17.2% and 27.7% at the same ages. CONCLUSION: The
      incidence of breast cancer is increased for FDRs of women with early-onset breast
      cancer irrespective of the BRCA status in the family. Risk increases with
      decreasing age and with increasing number of affected relatives. The incidences
      of prostate cancer, cervix cancer and nonmelanoma skin cancer are elevated for
      FDRs of early-onset breast cancer cases without a BRCA mutation, indicating a
      possible association between these cancers and early-onset breast cancer.

PMID- 14580255
TI  - Positron emission tomography agent 2-deoxy-2-[18F]fluoro-D-glucose has a
      therapeutic potential in breast cancer.
AB  - BACKGROUND: Novel approaches are needed for breast cancer patients in whom
      standard therapy is not effective. 2-Deoxy-2-[18F]fluoro-D-glucose (18F-FDG) was
      evaluated as a potential radiomolecular therapy agent in breast cancer animal
      models and, retrospectively, in patients with metastatic breast cancer. METHODS:
      Polyoma middle T antigen (PyMT) and mouse mammary tumor virus-NeuT transgenic
      mice with tumors 0.5-1 cm in diameter were imaged with 18F-FDG, and tumor to
      liver ratios (TLRs) were calculated. The radiotoxicity of 18F-FDG administration
      was determined in healthy mice. PyMT mice with small (0.15-0.17 cm) and large
      (more than 1 cm) tumors were treated with 2-4 mCi of 18F-FDG, and control C3H/B6
      mice with 3 mCi of 18F-FDG. At 10 days after treatment the tumors and control
      mammary glands were analyzed for the presence of apoptotic and necrotic cells.
      Five patients with breast cancer and metastatic disease were evaluated and
      standardized uptake values (SUVs) in tumors, maximum tolerated dose, and the
      doses to the tumor were calculated. RESULTS: Doses up to 5 mCi proved to be non
      radiotoxic to normal organs. The 18F-FDG uptake in mouse tumors showed an average
      TLR of 1.6. The treatment of mice resulted in apoptotic cell death in the small
      tumors. Cell death through the necrotic pathway was seen in large tumors, and was
      accompanied by tumor fragmentation and infiltration with leukocytes. Normal
      mammary tissues were not damaged. A human 18F-FDG dose delivering 200 rad to the
      red marrow (less than 5% damage) was calculated to be 4.76 Ci for a 70 kg woman,
      and the dose to the tumors was calculated to be 220, 1100 and 2200 rad for SUVs
      of 1, 5 and 10, respectively. CONCLUSION: We have shown that positrons delivered
      by 18F-FDG to mammary tumors have a tumoricidal effect on cancer cells. The study
      of breast cancer patients suggests that the tumor and normal organ dosimetry of
      18F-FDG makes it suitable for therapy of this malignancy.

PMID- 14580256
TI  - Log odds of carrying an Ancestral Mutation in BRCA1 or BRCA2 for a Defined
      personal and family history in an Ashkenazi Jewish woman (LAMBDA).
AB  - INTRODUCTION: Ancestral mutations in BRCA1 and BRCA2 are common in people of
      Ashkenazi Jewish descent and are associated with a substantially increased risk
      of breast and ovarian cancer. Women considering mutation testing usually have
      several personal and family cancer characteristics, so predicting mutation status
      from one factor alone could be misleading. The aim of this study was to develop a
      simple algorithm to estimate the probability that an Ashkenazi Jewish woman
      carries an ancestral mutation, based on multiple predictive factors. METHODS: We
      studied Ashkenazi Jewish women with a personal or family history of breast or
      ovarian cancer and living in Melbourne or Sydney, Australia, or with a previous
      diagnosis of breast or ovarian cancer and living in the UK. DNA samples were
      tested for the germline mutations 185delAG and 5382insC in BRCA1, and 6174delT in
      BRCA2. Logistic regression was used to identify, and to estimate the predictive
      strength of, major determinants. RESULTS: A mutation was detected in 64 of 424
      women. An algorithm was developed by combining our findings with those from
      similar analyses of a large study of unaffected Jewish women in Washington.
      Starting with a baseline score, a multiple of 0.5 (based on the logistic
      regression estimates) is added for each predictive feature. The sum is the
      estimated log odds ratio that a woman is a carrier, and is converted to a
      probability by using a table. There was good internal consistency. CONCLUSIONS:
      This simple algorithm might be useful in the clinical and genetic counselling
      setting. Comparison and validation in other settings should be sought.

PMID- 14580257
TI  - E-cadherin expression in primary carcinomas of the breast and its distant
      metastases.
AB  - INTRODUCTION: Aberrant expression of E-cadherin has been associated with the
      development of metastases in patients with breast cancer. Even though the
      expression of E-cadherin has been studied in primary breast tumors, little is
      known about its expression at the distant metastatic sites. We investigate the
      relationship between E-cadherin expression in primary breast carcinoma and their
      distant, non-nodal metastases. METHODS: Immunohistochemical analysis of E
      cadherin was performed in tissues from 30 patients with primary invasive breast
      carcinoma and their distant metastases. E-cadherin expression was evaluated as
      normal or aberrant (decreased when compared with normal internal positive
      controls, or absent). RESULTS: Twenty-two (73%) invasive carcinomas were ductal,
      and eight (27%) were lobular. Of the primary invasive ductal carcinomas, 55%
      (12/22) had normal E-cadherin expression and 45% (10/22) had aberrant expression.
      All of the metastases expressed E-cadherin with the same intensity as (12 tumors)
      or with stronger intensity than (10 tumors) the corresponding primaries. Of the
      invasive lobular carcinomas, one of eight (12%) primary carcinomas and none of
      the metastases expressed E-cadherin in the cell membranes, but they accumulated
      the protein in the cytoplasm. CONCLUSION: Aberrant E-cadherin expression is
      frequent in invasive ductal carcinomas that progress to develop distant
      metastases. Distant metastases consistently express E-cadherin, often more
      strongly than the primary tumor. Invasive lobular carcinomas have a different
      pattern of E-cadherin expression, suggesting a different role for E-cadherin in
      this form of breast carcinoma.

PMID- 14580258
TI  - aHIF but not HIF-1alpha transcript is a poor prognostic marker in human breast
      cancer.
AB  - BACKGROUND: Hypoxia-inducible factor-1alpha (HIF-1alpha) is part of a
      transcriptional factor that regulates genes involved in metabolic and vascular
      adaptation of tumours to oxygen restriction. A splicing variant lacking exon 14
      (sHIF-1alpha) encodes a truncated protein that competes with the normal HIF
      1alpha protein, decreasing its activity. A natural antisense transcript (aHIF)
      complementary to the 3'-untranslated region of HIF-1alpha mRNA was described
      recently. METHODS: With a semiquantitative multiplex reverse transcriptase-PCR
      (RT-PCR) assay, we assessed transcript concentrations of HIF-1alpha, sHIF-1alpha
      and aHIF in 110 patients with invasive breast carcinoma. RESULTS: We found a
      strong positive association between HIF-1alpha and sHIF-1alpha, sHIF-1alpha and
      aHIF, and an inverse correlation between HIF-1alpha /sHIF-1alpha and aHIF. aHIF
      transcript expression was associated with poor disease-free survival in
      univariate (P = 0.0038) and multivariate (P = 0.0016) analyses in this series of
      high-risk primary breast carcinomas. CONCLUSION: In our series of breast cancer
      patients, aHIF, and not HIF-1alpha transcript, is a marker of poor prognosis.

PMID- 14580259
TI  - Cell clusters overlying focally disrupted mammary myoepithelial cell layers and
      adjacent cells within the same duct display different immunohistochemical and
      genetic features: implications for tumor progression and invasion.
AB  - INTRODUCTION: Our previous studies detected focal disruptions in myoepithelial
      cell layers of several ducts with carcinoma in situ. The cell cluster overlying
      each of the myoepithelial disruptions showed a marked reduction in or a total
      loss of immunoreactivity for the estrogen receptor (ER). This is in contrast to
      the adjacent cells within the same duct, which were strongly immunoreactive for
      the ER. The current study attempts to confirm and expand previous observations on
      a larger scale. METHODS: Paraffin sections from 220 patients with ER-positive
      intraductal breast tumors were double immunostained with the same protocol
      previously used. Cross-sections of ducts lined by > or = 40 epithelial cells were
      examined for myoepithelial cell layer disruptions and for ER expression. In five
      selected cases, ER-negative cells overlying the disrupted myoepithelial cell
      layer and adjacent ER-positive cells within the same duct were separately
      microdissected and assessed for loss of heterozygosity and microsatellite
      instability. RESULTS: Of the 220 cases with 5698 duct cross-sections examined, 94
      showed disrupted myoepithelial cell layers with 405 focal disruptions. Of the 94
      cases, 79 (84%) contained only ER-negative cell clusters, nine (9.6%) contained
      both ER-negative and ER-positive cell clusters, and six (6.4%) contained only ER
      positive cell clusters overlying disrupted myoepithelial cell layers. Of the 405
      disruptions, 350 (86.4%) were overlain by ER-negative cell clusters and 55
      (13.6%) were overlain by ER-positive cell clusters (P < 0.01). Microdissected ER
      negative and ER-positive cells within the same duct from all five selected cases
      displayed a different frequency or pattern of loss of heterozygosity and/or
      microsatellite instability at 10 of the 15 DNA markers. CONCLUSIONS: Cells
      overlying focally disrupted myoepithelial layers and their adjacent counterparts
      within the same duct displayed different immunohistochemical and molecular
      features. These features potentially represent an early sign of the formation of
      a biologically more aggressive cell clone and the myoepithelial cell layer
      breakdown possibly associated with tumor progression or invasion.

PMID- 14580260
TI  - Cytoplasmic p21WAF1/CIP1 expression is correlated with HER-2/ neu in breast
      cancer and is an independent predictor of prognosis.
AB  - BACKGROUND: HER-2 (c-erbB2/Neu) predicts the prognosis of and may influence
      treatment responses in breast cancer. HER-2 activity induces the cytoplasmic
      location of p21WAFI/CIPI in cell culture, accompanied by resistance to apoptosis.
      p21WAFI/CIPI is a cyclin-dependent kinase inhibitor activated by p53 to produce
      cell cycle arrest in association with nuclear localisation of p21WAFI/CIPI. We
      previously showed that higher levels of cytoplasmic p21WAFI/CIPI in breast
      cancers predicted reduced survival at 5 years. The present study examined HER-2
      and p21WAFI/CIPI expression in a series of breast cancers with up to 9 years of
      follow-up, to evaluate whether in vitro findings were related to clinical data
      and the effect on outcome. METHODS: The CB11 anti-HER2 monoclonal antibody and
      the DAKO Envision Plus system were used to evaluate HER-2 expression in 73
      patients. p21WAFI/CIPI staining was performed as described previously using the
      mouse monoclonal antibody Ab-1 (Calbiochem, Cambridge, MA, USA). RESULTS: HER-2
      was evaluable in 67 patients and was expressed in 19% of cases, predicting
      reduced overall survival (P = 0.02) and reduced relapse-free survival (P = 0.004;
      Cox regression model). HER-2-positive tumours showed proportionately higher
      cytoplasmic p21WAFI/CIPI staining using an intensity distribution score (median,
      95) compared with HER-2-negative cancers (median, 47) (P = 0.005). There was a
      much weaker association between nuclear p21WAFI/CIPI and HER-2 expression (P =
      0.05), suggesting an inverse relationship between nuclear p21WAF1/CIP1 and HER-2.
      CONCLUSION: This study highlights a new pathway by which HER-2 may modify cancer
      behaviour. HER-2 as a predictor of poor prognosis may partly relate to its
      ability to influence the relocalisation of p21WAFI/CIPI from the nucleus to the
      cytoplasm, resulting in a loss of p21WAFI/CIPItumour suppressor functions.
      Cytoplasmic p21WAFI/CIPI may be a surrogate marker of functional HER-2 in vivo.

PMID- 14580262
TI  - Interferon-gamma Added During Bacillus Calmette-Guerin Induced Dendritic Cell
      Maturation Stimulates Potent Th1 Immune Responses.
AB  - Dendritic cells (DC) are increasingly prepared in vitro for use in immunotherapy
      trials. Mature DC express high levels of surface molecules needed for T cell
      activation and are superior at antigen-presentation than immature DC. Bacillus
      Calmette-Guerin (BCG) is one of several products known to induce DC maturation,
      and interferon (IFN)-gamma has been shown to enhance the activity of DC
      stimulated with certain maturation factors. In this study, we investigated the
      use of IFN-gamma in combination with the powerful maturation agent, BCG. The
      treatment of immature DC with IFN-gamma plus BCG led to the upregulation of CD54,
      CD80, and CD86 in comparison with BCG treatment alone. In MLR or recall immune
      responses, the addition of IFN-gamma at the time of BCG-treatment did not
      increase the number of antigen-specific T cells but enhanced the development of
      IFN-gamma-producing Th1 cells. In primary immune responses, on the other hand,
      BCG and IFN-gamma co-treated DC stimulated higher proportions of specific T cells
      as well as IFN-gamma secretion by these T cells. Thus the use of IFN-gamma during
      BCG-induced DC maturation differentially affects the nature of recall versus
      naive antigen-specific T-cell responses. IFN-gamma co-treatment with BCG was
      found to induce IL-12 and, in some instances, inhibit IL-10 secretion by DC.
      These findings greatly enhance the potential of BCG-matured dendritic cells for
      use in cancer immunotherapy.

PMID- 14580261
TI  - Quantitative determination, by real-time reverse transcription polymerase chain
      reaction, of aromatase mRNA in invasive ductal carcinoma of the breast.
AB  - BACKGROUND: Estrogen is a mitogenic factor that is implicated in the genesis and
      progression of breast cancer via its binding to estrogen receptor (ER)-alpha.
      Synthesis of estrogen in situ is believed to be catalyzed mainly by aromatase.
      Previous studies comparing the relative contributions from tumor cells and
      stromal cells to local estrogen synthesis, as assessed by immunohistochemical
      analysis, were quite controversial and no consistent relationship was found
      between the presence of aromatase and any clinicopathologic factor. In addition,
      previous studies into aromatase gene expression and clinicopathologic factors are
      limited. METHODS: We assessed the level of expression of aromatase mRNA, using
      quantitative real-time RT-PCR, in 162 cases of invasive ductal carcinoma of the
      breast. Associations between aromatase expression and different clinicopathologic
      factors were sought. RESULTS: It was found that aromatase mRNA was expressed at
      significantly higher levels in patients older than 50 years, in those without
      axillary lymph node involvement, in those with tumor size less than 2 cm, and in
      ER-alpha positive tumors. However, no relationship was found between aromatase
      mRNA expression and any other clinicopathologic factor, including histologic
      grade and progesterone receptor status. Patients with high levels of expression
      of aromatase mRNA tended to have a better prognosis than did those patients with
      low expression. CONCLUSION: These findings imply that ER-alpha and aromatase may
      be coexpressed in endocrine responsive patients. They may also indicate that
      aromatase expression could be a marker of endocrine responsiveness, and it may
      have prognostic implications for breast cancer progression.

PMID- 14580263
TI  - Styrylpyrone Derivative (SPD) induces apoptosis in a caspase-7-dependent manner
      in the human breast cancer cell line MCF-7.
AB  - BACKGROUND: Styrylpyrone derivative (SPD) is a plant-derived pharmacologically
      active compound extracted from Goniothalamus sp. Previously, we have reported
      that SPD inhibited the proliferation of MCF-7 human breast cancer cells by
      inducing apoptotic cell death, while having minimal effects on non-malignant
      cells. Here, we attempt to further elucidate the mode of action of SPD. RESULTS:
      We found that the intrinsic apoptotic pathway was invoked, with the accumulation
      of cytosolic cytochrome c and processing of the initiator caspase-9. Cleaved
      products of procaspase-8 were not detected. Next, the executioner caspase-7 was
      cleaved and activated in response to SPD treatment. To confirm that apoptosis was
      induced following caspase-7 activation, the caspase inhibitor Ac-DEVD-CHO was
      used. Pre-incubation of cells with this inhibitor reversed apoptosis levels and
      caspase-7 activity in SPD-treated cells to untreated levels. CONCLUSIONS: Taken
      together, these results suggest SPD as a potent antiproliferative agent on MCF-7
      cells by inducing apoptosis in a caspase-7-dependent manner.

PMID- 14580264
TI  - Chemically defined medium and Caenorhabditis elegans.
AB  - BACKGROUND: C. elegans has been established as a powerful genetic system. Use of
      a chemically defined medium (C. elegans Maintenance Medium (CeMM)) now allows
      standardization and systematic manipulation of the nutrients that animals
      receive. Liquid cultivation allows automated culturing and experimentation and
      should be of use in large-scale growth and screening of animals. RESULTS: We find
      that CeMM is versatile and culturing is simple. CeMM can be used in a solid or
      liquid state, it can be stored unused for at least a year, unattended actively
      growing cultures may be maintained longer than with standard techniques, and
      standard C. elegans protocols work well with animals grown in defined medium. We
      also find that there are caveats to using defined medium. Animals in defined
      medium grow more slowly than on standard medium, appear to display adaptation to
      the defined medium, and display altered growth rates as they change the
      composition of the defined medium. CONCLUSIONS: As was suggested with the
      introduction of C. elegans as a potential genetic system, use of defined medium
      with C. elegans should prove a powerful tool.

PMID- 14580265
TI  - HIV infection and risk factors among Bangkok prisoners, Thailand: a prospective
      cohort study.
AB  - BACKGROUND: Incarceration has been associated with HIV infection among injection
      drug users. However, data on HIV risk factors of the inmates during incarceration
      are rarely reported from Thailand. METHODS: A prospective cohort of 689 male
      inmates in a Bangkok central prison was studied during 2001-2002. Follow up
      visits were conducted for 5 months, with testing for HIV and other infections and
      interviewing of demographics and risk behaviors. RESULTS: Among 689 male inmates,
      half (50.9 %) were drug injectors. About 49% of the injectors had injection
      during incarceration. Most (94.9%) of the injectors had shared injection
      paraphernalia with others. Successful follow up rate was 98.7% after 2,581 person
      months observation. HIV incidence was 4.18 per 100 person--years among all
      inmates, and 11.10 per 100 person--years among the injection inmates.
      Multivariate analysis identified variables associated with HIV prevalence:
      history of injection [OR = 2.30, 95%CI: 1.91-2.77], positive urine opiate test
      [OR = 5.04, 95%CI: 2.63-9.67], history of attendance to drug withdrawal clinics
      [OR = 2.00, 95%CI: 1.19-3.35] and presence of tattoos on the body [OR = 1.23,
      95%CI: 1.01-1.52]. CONCLUSIONS: The main HIV risk factors of Bangkok inmates were
      those related to drug injection. Harm reduction measures and HIV intervention
      strategies should be implemented to prevent more spread of HIV among the inmates
      and into the community.

PMID- 14580266
TI  - How many repeated measures in repeated measures designs? Statistical issues for
      comparative trials.
AB  - BACKGROUND: In many randomized and non-randomized comparative trials, researchers
      measure a continuous endpoint repeatedly in order to decrease intra-patient
      variability and thus increase statistical power. There has been little guidance
      in the literature as to selecting the optimal number of repeated measures.
      METHODS: The degree to which adding a further measure increases statistical power
      can be derived from simple formulae. This "marginal benefit" can be used to
      inform the optimal number of repeat assessments. RESULTS: Although repeating
      assessments can have dramatic effects on power, marginal benefit of an additional
      measure rapidly decreases as the number of measures rises. There is little value
      in increasing the number of either baseline or post-treatment assessments beyond
      four, or seven where baseline assessments are taken. An exception is when
      correlations between measures are low, for instance, episodic conditions such as
      headache. CONCLUSIONS: The proposed method offers a rational basis for
      determining the number of repeat measures in repeat measures designs.

PMID- 14580267
TI  - The assassination of President John F Kennedy: a neuroforensic analysis--part 1:
      a neurosurgeon's previously undocumented eyewitness account of the events of
      November 22, 1963.
AB  - SUBSTANTIAL LITERATURE EXISTS on the assassination and subsequent pathological
      examination of President John F. Kennedy. The Warren Report, the United States
      Government's official report on the assassination, instead of providing
      definitive answers on the precise cause of President Kennedy's death, sparked
      intense and on-going debate. Since the publication of the Warren Report in
      September 1964, many issues have been woven into a wide array of theories
      concerning the assassination. One element continues to generate debate, namely,
      the exact sites of the wounds that President Kennedy sustained. A neuroforensic
      analysis of the wounds, from the perspective of the neurosurgeon, would establish
      a reasonable hypothesis for the mechanics of the shooting. Eyewitness accounts of
      the events surrounding the assassination represent one critical source of data
      for such an analysis. This report provides a previously undocumented
      neurosurgeon's eyewitness account of what transpired in Trauma Room 1 of Parkland
      Memorial Hospital on November 22, 1963.

PMID- 14580268
TI  - Risk of postoperative hemorrhage after intracranial surgery after early
      nadroparin administration: results of a prospective study.
AB  - OBJECTIVE: Early postoperative pharmacological prophylaxis of deep vein
      thrombosis after intracranial surgery is still a matter of debate because of
      concerns regarding the formation of postoperative hematoma. The objective of this
      study was to prospectively analyze the rate of postoperative hemorrhage during a
      3-year period of early postoperative administration of the low molecular weight
      heparin nadroparin (Fraxiparin) plus compression stockings in a large cohort of
      patients undergoing intracranial surgery. METHODS: A total of 2823 intracranial
      neurosurgical procedures, performed between June 1999 and 2002, were studied. Of
      these operations, 1319 (46.7%) were major intracranial surgical procedures (Group
      1). Group 2 comprised 1504 operations (53.3%) considered to be minor surgical
      procedures (e.g., shunt procedures, biopsies). All patients except those with
      transnasal transsphenoidal removal of pituitary tumors underwent early
      postoperative imaging (computed tomography or magnetic resonance imaging) to
      determine postoperative hemorrhage. All significant postoperative hematomas
      (defined as those requiring surgical evacuation because of relevant space
      occupation and/or neurological deterioration) were treated surgically.
      Prophylaxis of venous thromboembolic events included early (<24 h) postoperative
      administration of 0.3 ml nadroparin subcutaneously plus intra- and postoperative
      compression stockings until discharge. RESULTS: Forty-three major postoperative
      hemorrhages (1.5%) were observed after 2823 intracranial procedures (95%
      confidence interval, 1.1-2.05). Forty-two (3.2%) of 1319 postoperative hematomas
      occurred in patients undergoing major intracranial procedures (Group 1). There
      was only 1 (0.07%) significant hemorrhage after 1504 minor intracranial
      procedures (Group 2). A subgroup analysis of patients who needed preoperative
      anticoagulation because of medical comorbidity did not reveal an increased
      frequency of postoperative hematoma when anticoagulation was stopped 24 hours
      before surgery P = 0.1, chi(2) test; 95% confidence interval, 0.89-3.0).
      CONCLUSION: This report describes the largest prospective study conducted to date
      to determine the hemorrhage rate after early postoperative anticoagulation. The
      results support the concept of postoperative pharmacological thromboembolic
      prophylaxis in patients undergoing intracranial surgery.

PMID- 14580269
TI  - Hypofractionated conformal stereotactic radiotherapy for arteriovenous
      malformations.
AB  - OBJECTIVE: Arteriovenous malformations (AVMs) are congenital vascular lesions
      that are associated with high morbidity and mortality if left untreated. There
      are several options for treatment, including radiotherapy. Safe and effective
      single-fraction radiotherapy for patients with large AVMs has been considered
      difficult. METHODS: Between December 1986 and June 2001, 36 patients with
      cerebral AVMs were treated with hypofractionated conformal stereotactic
      radiotherapy at Umea University Hospital. Twenty-nine patients have been followed
      angiographically to date and are reported in this study. RESULTS: Twenty-four
      (83%) of 29 patients (mean AVM volume, 11.5 cm(3)) underwent complete
      obliteration of their AVMs. The rates of angiographically verified total
      obliteration at 2 years after treatment were 56% for AVMs 4 to 10 cm(3) and 50%
      for AVMs larger than 10 cm(3). The obliteration rate increased considerably with
      extended follow-up. Five years after treatment, the obliteration rates were 81%
      for AVMs 4 to 10 cm(3) and 70% for AVMs larger than 10 cm(3). CONCLUSION:
      Hypofractionated conformal stereotactic radiotherapy may be an important
      alternative to single-fraction radiotherapy in patients with large AVMs or AVMs
      located in eloquent areas, because it allows the administration of a higher
      radiation dose than is possible to deliver in single-fraction radiosurgery. With
      our technique of hypofractionated conformal stereotactic radiotherapy, the rate
      of obliterating AVMs was comparable to that of single-dose radiosurgery, although
      the volumes of the irradiated AVMs in our study were larger than those reported
      previously.

PMID- 14580270
TI  - Increases in cardiac output can reverse flow deficits from vasospasm independent
      of blood pressure: a study using xenon computed tomographic measurement of
      cerebral blood flow.
AB  - INTRODUCTION: Vasospasm after subarachnoid hemorrhage remains a management
      challenge. The accepted treatment involves hypertensive, hypervolemic,
      hemodilution therapy. However, there is variation in the application of this
      treatment. Most authors increase mean arterial pressure (MAP), which can be
      associated with significant morbidity. Others increase cardiac output (CO). In
      this study, we examined the relationship between volume status, CO, and MAP and
      cerebral blood flow (CBF) in the setting of vasospasm. METHODS: A xenon blood
      flow tomography-based system was used to quantitate CBF. Sixteen patients with
      vasospasm after subarachnoid hemorrhage were treated with hypervolemia,
      phenylephrine to increase MAP, or dobutamine to increase CO. Direct CBF
      measurements were obtained before and after treatment. A strength of this study
      is that only one variable (central venous pressure, MAP, or CO) was manipulated
      in each patient, and the effect of this change was measured immediately. RESULTS:
      With phenylephrine, mean MAP increased from 102.4 to 132.1 mm Hg. In regions of
      diminished CBF due to vasospasm, mean CBF increased from 19.2 to 33.7 ml/100
      g/min. Similarly, dobutamine increased the cardiac index from a mean of 4.1 to
      6.0 L/min/m(2) and slightly decreased MAP. CBF increased from a mean of 24.8 to
      35.4 ml/100 g/min. Both were statistically significant changes. With
      hypervolemia, the average central venous pressure increased from a mean of 5.4 to
      7.3 cm H(2)O; no changes in mean CBF were noted. CONCLUSION: This article reports
      the first human study that shows with direct measurements the independent
      influence of CO in the setting of vasospasm. Increases in CO without changes in
      MAP can elevate CBF. This finding has immediate clinical application because CO
      manipulation is much safer than increasing MAP. Because both interventions were
      equally efficacious, our protocol has been changed to augment CO as a first
      measure. Induced hypertension is reserved for patients in whom this initial
      treatment fails.

PMID- 14580271
TI  - Hyperperfusion syndrome: toward a stricter definition.
AB  - OBJECTIVE: Hyperperfusion syndrome is a rare and potentially devastating
      complication of carotid endarterectomy or carotid artery angioplasty and
      stenting. With the advent of new imaging techniques, we reviewed our experience
      with this phenomenon. METHODS: This report is a retrospective review of 129
      consecutive cases of carotid endarterectomy performed between June 1, 2000, and
      May 31, 2002, and 44 consecutive cases of carotid artery angioplasty and stenting
      performed between January 1, 1997, and May 31, 2002. We specifically searched for
      examples of patients who developed postprocedural nonthrombotic neurological
      deficits that typified the hyperperfusion syndrome. RESULTS: Seven cases of
      hyperperfusion syndrome occurred, four after endarterectomy (3.1% of carotid
      endarterectomy cases) and three after stenting (6.8% of stenting cases). The
      cases of hyperperfusion were classified as presenting with 1). acute focal edema
      (two cases with stroke-like presentation, attributable to edema immediately after
      revascularization), 2). acute hemorrhage (two cases of intracerebral hemorrhage
      immediately after stenting and one case immediately after endarterectomy), or 3).
      delayed classic presentation (two cases with seizures, focal motor weakness,
      and/or late intracerebral hemorrhage at least 24 hours after endarterectomy).
      CONCLUSION: Hyperperfusion syndrome may be more common and more variable in
      clinical presentation than previously appreciated.

PMID- 14580272
TI  - Management of acute cerebellar infarction: one institution's experience.
AB  - OBJECTIVE: The management of cerebellar infarctions is controversial. The aim of
      this study was to determine which patients require surgical treatment and which
      surgical procedure should be performed when a patient with a cerebellar
      infarction exhibits progressive neurological deterioration. METHODS: A total of
      44 patients (24 male and 20 female patients; average age, 56 yr) were treated at
      our institution for cerebellar infarctions in the past 8 years. Twenty-five
      patients received conservative treatment; two patients who were deeply comatose
      received no treatment. The remaining 17 patients underwent emergency surgery. Of
      those 17 patients, 8 underwent external ventricular drainage alone, 5 underwent
      external ventricular drainage as the first treatment plus secondary suboccipital
      craniectomy, and 4 underwent suboccipital craniectomy, with removal of necrotic
      tissue, as the first treatment. RESULTS: Of the 25 conservatively treated
      patients, 20 experienced good outcomes, 4 experienced moderate outcomes, and 1
      died as a result of pulmonary embolism. Of the 17 surgically treated patients, 10
      experienced good functional recoveries (7 treated with external ventricular
      drainage only and 3 treated with drainage followed by suboccipital craniectomy)
      and 3 survived with mild neurological deficits (one patient underwent
      ventriculostomy, one suboccipital craniectomy plus external ventricular drainage,
      and one suboccipital craniectomy only). The overall mortality rate was 13.6% (6
      of 44 patients). CONCLUSION: For patients with worsening levels of consciousness
      and radiologically evident ventricular enlargement, we recommend external
      ventricular drainage. We reserve surgical resection of necrotic tissue for
      patients whose clinical status worsens despite ventriculostomy, those for whom
      worsening is accompanied by signs of brainstem compression, and those with tight
      posterior fossae.

PMID- 14580273
TI  - Intraoperative cerebral angiography: superficial temporal artery method and
      results.
AB  - OBJECTIVE: To report the method for and results of intraoperative cerebral
      angiography performed via the superficial temporal artery, for assessment of
      cerebral aneurysm surgery. METHODS: All patients undergoing craniotomies for
      treatment of intracranial aneurysms were prospectively entered into a database. A
      policy of performing angiography via the superficial temporal artery in
      appropriate cases was instituted. This procedure was performed with retrograde
      catheterization of the superficial temporal artery, as it coursed over the
      zygomatic arch, with an 18-gauge, 1.88-inch, intravenous catheter and hand
      injection of contrast material, with intraoperative digital subtraction
      fluoroscopic guidance. RESULTS: Thirty-six patients who underwent 38 craniotomies
      for clipping of 43 aneurysms underwent intraoperative angiography via the
      superficial temporal artery. There were six unexpected findings (14%), including
      four unexpected arterial occlusions and two unexpected residual aneurysms. One
      aneurysm was observed to be patent when it was punctured, after intraoperative
      angiography had indicated no filling of the aneurysm. Additional clips were
      placed. Three patients (8%) developed multiple arterial infarctions in the
      territory of the injected carotid artery, for which multiple causes were
      possible. Adequate angiographic images could usually be obtained with this
      method. CONCLUSION: Intraoperative angiography via the superficial temporal
      artery is simple and is not associated with substantial complications. It is a
      reasonable alternative to transfemoral angiography for detection of adverse
      consequences of intracranial aneurysm clipping.

PMID- 14580274
TI  - Clinical characteristics of silent corticotrophic adenomas and creation of an
      internet-accessible database to facilitate their multi-institutional study.
AB  - OBJECTIVE: Silent corticotrophic adenomas (SCAs) of the pituitary gland present
      as clinically nonfunctioning sellar lesions, with normal serum and urine hormone
      testing results, but stain positively for adrenocorticotropic hormone in
      immunohistochemical analyses. These tumors are now more readily recognized, but
      determination of their natural history and responses to treatment is difficult
      because of their rarity. We report the diagnoses and outcomes for a series of
      patients with SCAs, and we describe the creation of an Internet-accessible
      database (www.hsc.virginia.edu/neuro/neurosurgery/pituitary.html) for collection
      of multi-institutional data on these lesions. METHODS: The medical records of
      patients with documented SCAs who were treated at the University of Virginia
      between 1991 and 2002 were reviewed. A comprehensive data collection form was
      then created and posted online. RESULTS: Twenty-seven patients with SCAs were
      identified, with a female predominance (70%, P = 0.04). Headache was the most
      common presenting symptom (70%), followed by visual field deficits (52%), acute
      or subacute pituitary apoplexy (33%), cavernous sinus syndrome (18.5%), and
      hypopituitarism (11.1%). Extrasellar extension was noted for 92.6% of patients on
      preoperative magnetic resonance imaging scans. Transsphenoidal surgery was
      performed for all patients. Follow-up information was available for all patients
      (median, 60 mo; range, 3-254 mo). Postoperatively, 33% of patients received
      radiotherapy. Recurrence was noted for 37% of all patients and 41.7% of patients
      who did not receive postoperative radiotherapy. CONCLUSION: SCAs, although
      clinically nonfunctioning, may behave like aggressive adrenocorticotropic hormone
      secreting adenomas and therefore should receive vigorous follow-up monitoring,
      with consideration being given to the recommendation of radiotherapy in cases
      with residual tumor.

PMID- 14580275
TI  - Stereotactic radiosurgery as an alternative to fractionated radiotherapy for
      patients with recurrent or residual nonfunctioning pituitary adenomas.
AB  - OBJECTIVE: To evaluate tumor control rates and complications after stereotactic
      radiosurgery for patients with nonfunctioning pituitary adenomas. METHODS:
      Between 1992 and 2000, 33 patients underwent radiosurgery for treatment of
      nonfunctioning pituitary adenomas. Thirty-two patients (97%) had undergone one or
      more previous tumor resections. Twenty-two patients (67%) had enlarging tumors
      before radiosurgery. The median tumor margin dose was 16 Gy (range, 12-20 Gy).
      The median follow-up period after radiosurgery was 43 months (range, 16-106 mo).
      RESULTS: Tumor size decreased for 16 patients, remained unchanged for 16
      patients, and increased for 1 patient. The actuarial tumor growth control rates
      at 2 and 5 years after radiosurgery were 97%. No patient demonstrated any decline
      in visual function. Five of 18 patients (28%) with anterior pituitary function
      before radiosurgery developed new deficits, at a median of 24 months after
      radiosurgery. The actuarial risks of developing new anterior pituitary deficits
      were 18 and 41% at 2 and 5 years, respectively. No patient developed diabetes
      insipidus. CONCLUSION: Stereotactic radiosurgery safely provides a high tumor
      control rate for patients with recurrent or residual nonfunctioning pituitary
      adenomas. However, despite encouraging early results, more long-term information
      is needed to determine whether radiosurgery is associated with lower risks of new
      endocrine deficits and radiation-induced neoplasms, compared with fractionated
      radiotherapy.

PMID- 14580276
TI  - Stimulation of the subthalamic nucleus in Parkinson's disease does not produce
      striatal dopamine release.
AB  - OBJECTIVE: The subthalamic nucleus (STN) is a target in the surgical treatment of
      Parkinson's disease (PD). The mechanism by which electrical stimulation of the
      STN ameliorates symptoms of PD remains unknown. One consistent aspect of STN
      stimulation is the ability to reduce the dosage of dopaminergic medications;
      sometimes they can be eliminated altogether. Furthermore, nigrostriatal
      projection axons are apposed to the dorsal surface of the STN and are likely
      affected by the application of current in this region. We sought to determine
      whether STN stimulation could release endogenous striatal dopamine. METHODS: Five
      patients with PD, who had previously undergone surgical implantation of bilateral
      STN stimulators, underwent [(11)C]raclopride positron emission tomographic
      scanning. l-dopa was withheld for 12 hours, and both stimulators were turned off
      9 hours before scanning. We assayed for striatal dopamine release by measuring
      radioligand displacement as a consequence of turning on the right STN stimulator
      after 45 minutes of a 90-minute [(11)C]raclopride infusion. Patients were
      evaluated with the motor section of the Unified Parkinson's Disease Rating Scale
      before and after the studies. RESULTS: Comparisons between the right and left
      striata, before and after right STN stimulation, demonstrated no significant
      differences in [(11)C]raclopride binding, despite significant improvements in
      Unified Parkinson's Disease Rating Scale motor scores with unilateral stimulation
      (mean improvement, 26.0 +/- 16.4%; P < 0.05). This finding was also noted when
      the striatum was partitioned into dorsal and ventral caudate and putamen and the
      four regions were analyzed separately. CONCLUSION: Our results suggest that STN
      stimulation does not mediate its anti-PD effects via the release of dopamine, as
      assessed with [(11)C]raclopride displacement.

PMID- 14580277
TI  - Surgical outcomes of 111 spinal accessory nerve injuries.
AB  - OBJECTIVE: Iatrogenic injury to the spinal accessory nerve is not uncommon during
      neck surgery involving the posterior cervical triangle, because its superficial
      course here makes it susceptible. We review injury mechanisms, operative
      techniques, and surgical outcomes of 111 surgical repairs of the spinal accessory
      nerve. METHODS: This retrospective study examines clinical and surgical
      experience with spinal accessory nerve injuries at the Louisiana State University
      Health Sciences Center during a period of 23 years (1978-2000). Surgery was
      performed on the basis of anatomic and electrophysiological findings at the time
      of operation. Patients were followed up for an average of 25.6 months. RESULTS:
      The most frequent injury mechanism was iatrogenic (103 patients, 93%), and 82
      (80%) of these injuries involved lymph node biopsies. Eight injuries were caused
      by stretch (five patients) and laceration (three patients). The most common
      procedures were graft repairs in 58 patients. End-to-end repair was used in 26
      patients and neurolysis in 19 patients if the nerve was found in continuity with
      intraoperative electrical evidence of regeneration. Five neurotizations, two
      burials into muscle, and one removal of ligature material were also performed.
      More than 95% of patients treated by neurolysis supported by positive nerve
      action potential recordings improved to Grade 4 or higher. Of 84 patients with
      lesions repaired by graft or suture, 65 patients (77%) recovered to Grade 3 or
      higher. The average graft length was 1.5 inches. CONCLUSION: Surgical exploration
      and repair of spinal accessory nerve injuries is difficult. With perseverance,
      however, these patients with complete or severe deficits achieved favorable
      functional outcomes through operative exploration and repair.

PMID- 14580278
TI  - Surgical management and results of 135 tibial nerve lesions at the Louisiana
      State University Health Sciences Center.
AB  - OBJECTIVE: This retrospective study presents 33 years of clinical and surgical
      experience with 135 tibial nerve lesions to review operative techniques and their
      results and to provide management guidelines for the proper selection of surgical
      candidates. METHODS: Between 1967 and 1999, 135 patients with tibial nerve
      lesions at the knee level or below were managed surgically at the Louisiana State
      University Health Sciences Center. We reviewed these cases. RESULTS: Of the 135
      cases, traumatic injury accounted for 71, tarsal tunnel syndrome for 46, and
      nerve sheath tumor for 18. Of 22 lesions not in continuity, functional recovery
      of Grade 3 or better was achieved in 4 (67%) of 6 patients who required end-to
      end suture repair and 11 (69%) of 16 patients who required graft repair. One
      hundred thirteen tibial nerve lesions in continuity underwent primarily external
      or internal neurolysis or resection of the lesions. A few received end-to-end
      suture or graft repair. Direct intraoperative recording of nerve action
      potentials guided case management decisions. Among the 113 patients with lesions
      in continuity, 76 (81%) of 94 patients receiving neurolysis, 5 (83%) of 6
      receiving suture repair, and 11 (85%) of 13 receiving graft repair recovered
      function to Grade 3 or better. Repair results were best in patients with
      recordable nerve action potentials treated by external neurolysis. Results were
      poor in a few patients with very lengthy lesions in continuity and in reoperated
      patients with tarsal tunnel syndrome. CONCLUSION: Surgical exploration and repair
      of tibial nerve lesions, including nerve sheath tumors and tarsal tunnel
      syndromes, achieved excellent outcomes.

PMID- 14580279
TI  - Zones of approach for craniofacial resection: minimizing facial incisions for
      resection of anterior cranial base and paranasal sinus tumors.
AB  - OBJECTIVE: Anterior cranial base tumors are surgically resected with combined
      craniofacial approaches that frequently involve disfiguring facial incisions and
      facial osteotomies. The authors outline three operative zones of the anterior
      cranial base and paranasal sinuses in which tumors can be resected with three
      standard surgical approaches that minimize transfacial incisions and extensive
      facial osteotomies. METHODS: The zones were defined by performing dissections on
      10 cadaveric heads and by evaluating radiographic images of patients with
      anterior cranial base tumors. The three approaches performed on each cadaver were
      transbasal, transmaxillary, and extended transsphenoidal. RESULTS: Three zones of
      approach were defined for accessing tumors of the anterior cranial base, nasal
      cavity, and paranasal sinuses. Zone 1 is exposed by the transbasal approach,
      which is limited anteriorly by the supraorbital rim, posteriorly by the optic
      chiasm and clivus, inferiorly by the palate, and laterally by the medial orbital
      walls. This approach allows access to the entire anterior cranial base, nasal
      cavity, and the majority of maxillary sinuses. The limitation imposed by the
      orbits results in a blind spot in the superolateral extent of the maxillary
      sinus. Zone 2 is exposed by a sublabial maxillotomy approach and accesses the
      entire maxillary sinus, including the superolateral blind spot and the
      ipsilateral anterior cavernous sinus. However, access to the anterior cranial
      base is limited. Zone 3 is exposed by the transsphenoidal approach. This approach
      accesses the midline structures but is limited by the lateral nasal walls and
      intracavernous carotid arteries. An extended transsphenoidal approach allows
      further exposure to the anterior cranial base, clivus, or cavernous sinuses. The
      use of the endoscope facilitates tumor resection in the nasal cavity and
      paranasal sinuses. CONCLUSION: The operative zones outlined offer minimally
      invasive craniofacial approaches to accessing lesions of the anterior cranial
      base and paranasal sinuses, obviating facial incisions and facial osteotomies.
      Case illustrations demonstrating the approach selection paradigm are presented.

PMID- 14580280
TI  - Microsurgical keyhole approach for middle fossa arachnoid cyst fenestration.
AB  - OBJECTIVE: The optimal surgical treatment for symptomatic temporal arachnoid
      cysts is controversial. Therapeutic options include cyst shunting, endoscopic
      fenestration, and craniotomy for fenestration. We reviewed the results for
      patients who were treated primarily with craniotomy and fenestration at our
      institution, to provide a baseline for comparisons of the efficacies of other
      treatment modalities. METHODS: A retrospective review of data for 50 children who
      underwent keyhole craniotomy for fenestration of temporal arachnoid cysts between
      1994 and 2001 was performed after institutional review board approval. During
      that period, the first-line treatment for all symptomatic middle fossa arachnoid
      cysts was microcraniotomy for fenestration. Microsurgical dissection to create
      communications between the cyst cavity and basal cisterns was the goal. All
      patient records were reviewed and numerous variables related to presentation,
      cyst size and classification, treatment, cyst resolution, symptom resolution,
      follow-up periods, and cyst outcomes were recorded. RESULTS: Fifty temporal
      arachnoid cysts in 50 treated patients were identified. The average age at the
      time of surgery was 68 +/- 57.2 months. The follow-up periods averaged 36 months.
      There were 34 male and 16 female patients in the series. Twenty-six cysts were on
      the left side. Indications for surgery included intractable headaches (45%),
      increasing cyst size (21%), seizures (25%), and hemiparesis (8%). The symptoms
      most likely to improve were hemiparesis (100%) and abducens nerve palsies.
      Headaches (67%) and seizure disorders (50%) were less likely to improve. Nine
      patients exhibited progressive increases in cyst size in serial imaging studies.
      Those patients were monitored for a mean of 40 +/- 23 months before intervention.
      In the entire series, 82% of patients demonstrated decreases in cyst size in
      serial imaging studies. Of those patients, 18% demonstrated complete cyst
      effacement. Overall, 83% of patients with Grade II cysts and 75% of patients with
      Grade III cysts exhibited evidence of decreases in cyst size in long-term
      monitoring. Two patients required shunting after craniotomy (4%). Hospital stays
      averaged 3.4 days. Total surgical times averaged 115 minutes. No significant
      blood loss occurred (5-50 ml). Complications included spontaneously resolving
      pseudomeningocele (10%), transient Cranial Nerve III palsy (6%), cerebrospinal
      fluid leak (6%), subdural hematoma (4%), and wound infection (2%). CONCLUSION: A
      microsurgical keyhole approach to arachnoid cyst fenestration is a safe effective
      method for treating middle fossa cysts. This procedure can be performed with
      minimal morbidity via a minicraniotomy. Compared with an endoscopic approach,
      better control of hemostasis can be obtained, because of the ability to use
      bipolar forceps and other standard instruments. The operative time and length of
      hospital stay were not excessively increased.

PMID- 14580281
TI  - Surgery of the subthalamic nucleus: use of movement-related neuronal activity for
      surgical navigation.
AB  - THE BASAL GANGLIA have important roles in somatic motor, oculomotor, limbic, and
      associative functions. These functions are represented in anatomically distinct
      territories in each basal ganglion nucleus. During surgery of the subthalamic
      nucleus for Parkinson's disease, the primary goal is to influence the physiology
      of the motor territory without affecting nonmotor areas. This article describes
      the use of movement-related cellular activity during single-unit microelectrode
      mapping to identify and to navigate within the motor territory of the subthalamic
      nucleus.

PMID- 14580282
TI  - Implantation of laminotomy electrodes for spinal cord stimulation in spinal
      anesthesia with intraoperative dorsal column activation.
AB  - OBJECTIVE: To optimize the technique of implanting laminotomy plate electrodes
      for spinal cord stimulation and to minimize the discomfort of the patients during
      surgery. This operation is often performed while the patient is under local
      anesthesia, which is very stressful for the patient, or under general anesthesia,
      which precludes the use of test stimulation. An alternative approach is to
      perform the implantation with a spinal anesthetic and to examine whether
      stimulation-induced paresthesiae can still be evoked to guide the positioning of
      the electrode. METHODS: Spinal anesthesia was induced by bupivacaine (12.5-20
      mg), which produced complete motor block and anesthesia up to a midthoracic
      level. After a single-level laminotomy (thoracic vertebrae 9-11) a four-pole
      plate electrode was inserted into the epidural space. Stimulation was applied
      with commonly used parameters, and the electrode was positioned so that the
      paresthesiae covered the painful region. RESULTS: In 19 patients (20 procedures)
      with different forms of neuropathic pain, implantation of laminotomy plate
      electrodes could be performed under spinal anesthesia without problems. In all
      patients, it was possible to evoke paresthesiae, the distribution of which could
      be reproduced postoperatively. The paresthesia thresholds during surgery were
      only moderately higher than those recorded after implantation (mean, 3.1 versus
      2.1 V, respectively). During an interview after the intervention, no patient
      reported that he or she had experienced surgery as painful or uncomfortable.
      CONCLUSION: Implantation of laminotomy electrodes can be performed conveniently
      with spinal anesthesia because it minimizes discomfort for the patient and
      enables the use of intraoperative test stimulation to guide the positioning of
      the electrode. In spite of the total motor block and anesthesia, paresthesiae
      representing the activation of the dorsal columns can be evoked and are well
      perceived, and the thresholds are not abnormally high. This observation supports
      the notion that the subarachnoidal anesthetic agent acts predominantly on the
      spinal rootlets rather than on the spinal afferent pathways.

PMID- 14580284
TI  - A new classification for facial pain.
AB  - PURPOSE: A patient-oriented classification scheme for facial pains commonly
      encountered in neurosurgical practice is proposed. CONCEPT: This classification
      is driven principally by the patient's history. RATIONALE: The scheme
      incorporates descriptions for so-called "atypical" trigeminal neuralgias and
      facial pains but minimizes the pejorative, accepting that the physiology of
      neuropathic pains could reasonably encompass a variety of pain sensations, both
      episodic and constant. Seven diagnostic labels result: trigeminal neuralgia Types
      1 and 2 refer to patients with the spontaneous onset of facial pain and either
      predominant episodic or constant pain, respectively. Trigeminal neuropathic pain
      results from unintentional injury to the trigeminal nerve from trauma or surgery,
      whereas trigeminal deafferentation pain results from injury to the nerve by
      peripheral nerve ablation, gangliolysis, or rhizotomy in an intentional attempt
      to treat either trigeminal neuralgia or other facial pain. Postherpetic neuralgia
      follows a cutaneous herpes zoster outbreak (shingles) in the trigeminal
      distribution, and symptomatic trigeminal neuralgia results from multiple
      sclerosis. The final category, atypical facial pain, is synonymous with facial
      pain secondary to a somatoform pain disorder. Atypical facial pain can be
      suspected but not diagnosed by history and can be diagnosed only with detailed
      and objective psychological testing. CONCLUSION: This diagnostic classification
      would allow more rigorous and objective natural history and outcome studies of
      facial pain in the future.

PMID- 14580283
TI  - Dosimetric comparison of CyberKnife with other radiosurgical modalities for an
      ellipsoidal target.
AB  - OBJECTIVE: To compare treatment plans obtained with the CyberKnife (CK) (Accuray,
      Inc., Sunnyvale, CA) with those of other commonly used radiosurgical modalities,
      such as the gamma knife (GK), linear accelerator multiple arcs, conformally
      shaped static fields, and intensity-modulated radiotherapy (IMRT). METHODS: An
      ellipsoidal simulated target was chosen centrally located in a three-dimensional
      model of a patient's head acquired with magnetic resonance or computed
      tomographic imaging. It was 25 mm in diameter and 35 mm long. The aims of
      treatment plans were 100% target volume coverage with an appropriate isodose
      line, minimum radiation dose to normal tissue, and clinically acceptable
      delivery. These plans were evaluated by use of a dose-volume histogram and other
      commonly used radiosurgical parameters such as target coverage, homogeneity
      index, and conformity index. RESULTS: All selected treatment modalities were
      equivalent in providing full target coverage. For dose homogeneity, all
      modalities except for multiple isocenter plans for GK (homogeneity index, 2.0)
      were similar (homogeneity index, congruent with 1.25). Dose conformity was
      essentially equivalent for all treatment plans except for IMRT, which had a
      slightly higher value (conformity index, congruent with 1.27). There was a
      substantial variation in the radiation dose to normal tissue between the studied
      modalities, particularly at the lower dose levels. CONCLUSION: CK plans seemed to
      be more flexible for a given target size and shape. For a target of limited
      volume and essentially of any shape, one could obtain similarly good conformal
      dosimetry with CK and GK. For a regular-shaped but other than spherical target,
      homogeneous dose distribution could be obtained with all selected modalities
      except for multiple isocenters, linear accelerator multiple arcs, or GK. Both
      IMRT and conformally shaped static fields offered good alternative treatment
      modalities to CK, GK, or linear accelerator multiple arc radiosurgery, with
      slightly inferior dosimetry in conformity (IMRT).

PMID- 14580285
TI  - Advanced cancer genetics in neurosurgical research.
AB  - RAPID ADVANCES IN the technology used to study nucleic acids have revealed a
      great deal regarding the underlying biology of cancer. Most cancers arise as a
      result of chromosomal rearrangements and deoxyribonucleic acid mutations that
      lead to the activation of proto-oncogenes and loss of function of tumor
      suppressor genes. There are a number of different molecular routes that lead to
      these common goals, necessitating several different techniques of mutational
      analysis. Although many of these techniques can be difficult in practice, most
      are conceptually simple. We discuss several of the current techniques in
      cytogenetics and molecular genetics that are widely used in cancer biology
      laboratories. Understanding the molecular events that lead to cancer should allow
      the future development of targeted, nontoxic therapeutics similar to modern-day
      antibiotics. These technologies are being progressively applied in clinical
      neurosurgery, where they will be used to detect, diagnose, stratify, and treat
      cancers of the nervous system. High demand from an increasingly educated patient
      population means that neurosurgeons will need to be familiar with many of these
      techniques.

PMID- 14580286
TI  - Overexpression of rat heat shock protein 70 reduces neuronal injury after
      transient focal ischemia, transient global ischemia, or kainic acid-induced
      seizures.
AB  - OBJECTIVE: Transgenic (Tg) mice overexpressing rat heat shock protein 70 (hsp70)
      demonstrated less infarction than did wild-type (WT) littermates after permanent
      focal cerebral ischemia. The purpose of this study was to determine whether
      neuronal injury and apoptosis were reduced in hsp70 Tg mice after transient focal
      ischemia. The effects of hsp70 overexpression were also evaluated after transient
      global ischemia or kainic acid (KA)-induced seizures, to verify the results in
      other excitotoxic stress models. METHODS: Transient focal ischemia was produced
      with middle cerebral artery occlusion via intraluminal suture cannulation.
      Infarction volumes were assessed 24 hours after 30 minutes of middle cerebral
      artery occlusion. Transient global ischemia was produced with 25 minutes of
      bilateral common carotid artery occlusion. KA (30 mg/kg) was administered
      subcutaneously, and seizure activity was evaluated. The number of eosinophilic
      neurons was assessed in the CA1 region 72 hours after bilateral common carotid
      artery occlusion and in the CA3 region 24 hours after KA administration. RESULTS:
      The infarction volume after transient middle cerebral artery occlusion was
      significantly smaller in hsp70 Tg mice than in WT mice (9.1 +/- 5.7 mm(3) versus
      22.4 +/- 16.8 mm(3), P < 0.05). The number of eosinophilic neurons in the CA1
      area after bilateral common carotid artery occlusion and in CA3 after KA
      injection was significantly lower in hsp70 Tg mice than in WT mice (949.1 +/-
      1095.5 versus 2406.9 +/- 1380.3, P < 0.05, and 33.8 +/- 45.3 versus 119.4 +/-
      112.1, P < 0.05, respectively). Fewer terminal deoxynucleotidyl transferase
      mediated biotinylated deoxyuridine triphosphate nick end-labeling-positive cells
      were observed in hsp70 Tg mice than in WT mice in each model. CONCLUSION: The
      results demonstrate that overexpression of hsp70 reduces neuronal injury after
      ischemia and seizures. The reduction in the number of terminal deoxynucleotidyl
      transferase-mediated biotinylated deoxyuridine triphosphate nick end-labeling
      positive cells in hsp70 Tg mice suggests that hsp70 overexpression might reduce
      apoptotic cell death.

PMID- 14580288
TI  - Severity and duration of hyperalgesia in rat varies with type of nerve lesion.
AB  - OBJECTIVE: To learn how lesions with differing capacity for nerve regeneration
      affect the severity and duration of hyperalgesia in an animal model of
      neuropathic pain. METHODS: Three groups of rats were studied: 1). L5 nerve root
      crush (favorable for regeneration); 2). L5 root ligation and section; and 3).
      sham-operated group. An experimenter who did not know the rats' groups tested the
      animals for hyperalgesia to mechanical and cold stimuli. RESULTS: Measures of
      adverseness of mechanical and cooling stimuli for the crush group and
      ligation/cut groups were significantly higher than for the sham-operated group (P
      < 0.001 for both) for the first 30 days after lesioning. By 40 days, the crush
      group recovered from mechanical hyperalgesia, whereas the ligation/cut group
      continued to have significant hyperalgesia. At this time, both lesion groups
      displayed hyperalgesia to the cooling stimulus (P < 0.001), but the hyperalgesia
      in the ligation/cut group was significantly greater (P < 0.01). No recovery from
      cooling hyperalgesia was evident during the 54-day period of observation.
      Histological studies of the sciatic nerve indicated higher numbers of
      regenerating fibers in the crush group compared with the ligation/cut group.
      CONCLUSION: This study demonstrates that axotomy, regardless of how it is
      induced, produces hyperalgesia to both mechanical and cold stimuli. However, the
      lesion that favors regeneration is associated with earlier signs of recovery from
      mechanical hyperalgesia and less severe signs of cooling hyperalgesia. The data
      support the hypothesis that inputs from the injured afferents play an ongoing
      role in neuropathic pain from nerve injury. Nerve ligation induces more severe
      and more sustained behavioral signs of pain than nerve crush.

PMID- 14580287
TI  - Toward optimal tissue sealants for neurosurgery: use of a novel hydrogel sealant
      in a canine durotomy repair model.
AB  - OBJECTIVE: Watertight dural repairs are difficult to achieve, and cerebrospinal
      fluid leakage causes complications and extends hospital stays. Therefore, a novel
      synthetic hydrogel film was evaluated as an adjunct to dural closure in a canine
      model. METHODS: The self-polymerizing, absorbable, and biocompatible hydrogel was
      sprayed onto tissue and formed a flexible, adherent sealant. A 2-cm incision of
      cranial dura and arachnoid was created in 26 adult dogs and loosely repaired.
      Hydrogel was applied over the 2-mm dural gap in 13 dogs; 13 control dogs received
      no hydrogel application. RESULTS: All dogs remained neurologically intact.
      Valsalva tests conducted at 1, 4, 7, and 56 days were associated with mean
      leakage pressures (+/- standard error of the mean) of 5 +/- 0, 5 +/- 0, 7 +/- 2,
      and 13 +/- 8 cm H(2)O in the controls and of 53 +/- 2, 37 +/- 11, 42 +/- 6, and
      48 +/- 4 in the treated animals (P = 0.001, 0.053, 0.010, 0.035, respectively, at
      each time point; one-tailed t test). Histopathological analysis revealed minimal
      changes. CONCLUSION: The hydrogel-treated animals exhibited normal progression of
      dural healing, no dural adhesions, and no underlying effects on the brain.
      Although dural healing progressed normally, the control animals displayed marked
      peridural adhesions. The results of this in vivo study suggest that hydrogels,
      such as that used here, may significantly decrease cerebrospinal fluid leakage,
      thereby increasing the safety and effectiveness of dural closure in patients and
      facilitating surgical reexploration.

PMID- 14580289
TI  - Multiple intracranial arterial stenoses around the circle of Willis in
      association with Graves' disease: report of two cases.
AB  - OBJECTIVE AND IMPORTANCE: The association of Graves' disease with multiple
      intracranial arterial stenoses is rare. CLINICAL PRESENTATION: We report on two
      Japanese women who experienced the concurrence of Graves' disease and cerebral
      ischemia attributable to multiple intracranial arterial stenoses around the
      circle of Willis. Clinically, these patients demonstrated hyperthyroidism,
      goiter, ophthalmopathy, and ensuing ischemic strokes. Cerebral angiography
      demonstrated multiple intracranial arterial stenoses around the circle of Willis
      in both cases. These cases did not meet the full diagnostic criteria for moyamoya
      disease, in that there were no abnormal, net-like, collateral vessels, but the
      other clinical and angiographic findings were consistent with this condition.
      INTERVENTION: After normalization of their hormonal conditions, the patients
      underwent cerebral revascularization procedures. Both patients achieved excellent
      recoveries and returned to normal daily life after treatment. CONCLUSION:
      Multiple intracranial arterial stenoses and Graves' disease may occur
      simultaneously. Such cases may offer new insights into the pathogenesis of these
      two conditions. It is important to study more patients with this dual condition,
      to obtain more evidence of the relationship between genetic and immunogenic
      backgrounds.

PMID- 14580290
TI  - Recurrent spontaneous spinal cerebrospinal fluid leak associated with "nude nerve
      root" syndrome: case report.
AB  - OBJECTIVE AND IMPORTANCE: Spontaneous spinal cerebrospinal fluid (CSF) leaks have
      been noted occasionally at multiple sites in the same patient, but recurrent
      spontaneous spinal CSF leaks have not been documented. We describe a patient with
      a recurrent CSF leak who was found at surgery to have an absence of the entire
      nerve root sleeve at multiple thoracic levels. CLINICAL PRESENTATION: A 29-year
      old woman bodybuilder noted an excruciating orthostatic headache associated with
      nausea. The neurological examination was unremarkable, and a magnetic resonance
      imaging examination showed the typical changes of intracranial hypotension.
      Computed tomographic myelography showed an extensive bilateral lower cervical CSF
      leak. INTERVENTION: The patient underwent bilateral lower cervical nerve root
      explorations, and several small dural holes were found. The CSF leaks were
      repaired, but 3 months later, computed tomographic myelography showed a new CSF
      leak in the midthoracic area. A thoracic laminectomy was performed, and several
      nerve roots were found to be completely devoid of dura. After the CSF leaks were
      repaired, there was significant improvement in her headaches. CONCLUSION: A
      recurrent spontaneous spinal CSF leak may occur in patients with intracranial
      hypotension at a site previously documented not to be associated with a CSF leak.
      Absent nerve root sleeves may be found in patients with spontaneous spinal CSF
      leaks ("nude nerve root" syndrome), and these patients may be at increased risk
      of developing a recurrent CSF leak.

PMID- 14580291
TI  - Acute syringomyelia: case report.
AB  - OBJECTIVE AND IMPORTANCE: Syringomyelia is generally regarded as a chronic,
      slowly progressive disorder. We describe a case of acute dilation of the central
      canal of the spinal cord that presented with rapidly progressive segmental signs.
      CLINICAL PRESENTATION: A 29-year-old female patient who had previously undergone
      surgical treatment for a Chiari I malformation, syringomyelia, and hydrocephalus
      presented with an 8-day history of headaches, progressive paraparesis, and
      urinary retention. Magnetic resonance imaging scans demonstrated panventricular
      hydrocephalus in association with a holocord syrinx that extended to the obex.
      Magnetic resonance imaging scans that had been coincidentally obtained just 3
      days before the onset of symptoms had revealed no evidence of hydrocephalus or
      syringomyelia. INTERVENTION: The patient underwent emergency revision of a failed
      ventriculoperitoneal shunt. Postoperatively, there was prompt resolution of the
      syringomyelia, hydrocephalus, and associated neurological deficits. CONCLUSION:
      Among patients with communicating syringomyelia, the central canal of the spinal
      cord participates as a "fifth ventricle" and can undergo rapid dilation in
      association with acute hydrocephalus. Appropriate treatment in such cases
      involves placement of a ventriculoperitoneal shunt.

PMID- 14580292
TI  - Endoscopic third ventriculostomy with cystoventricular stent placement in the
      management of dandy-walker malformation: technical case report of three patients.
AB  - OBJECTIVE AND IMPORTANCE: Dandy-Walker malformation has conventionally been
      managed with placement of cystoperitoneal or ventriculoperitoneal shunts.
      However, associated aqueductal obstruction requires simultaneous drainage of both
      the supratentorial and infratentorial compartments. CLINICAL PRESENTATION: Three
      children with Dandy-Walker malformation and aqueductal obstruction were managed
      with endoscopic third ventriculostomy and placement of a stent from the third
      ventricle to the posterior fossa cyst. INTERVENTION: After an endoscopic third
      ventriculostomy was performed, the stent was placed from the third ventricle to
      the posterior fossa cyst through the thinnest part of the posteroinferior wall of
      the aqueduct. There was no operative morbidity. In one patient, the stent was
      malpositioned, requiring a repositioning. The endoscopic third ventriculostomy
      was successful in two patients, whereas it failed in one, requiring a
      ventriculoperitoneal shunt placement. CONCLUSION: Cystoventricular stent
      placement with endoscopic third ventriculostomy is a promising alternative in
      patients with Dandy-Walker malformation with aqueductal obstruction.

PMID- 14580293
TI  - Removal of an anterior spinal dermoid cyst with fenestra corpectomy in Klippel
      Feil syndrome: technical case report.
AB  - OBJECTIVE AND IMPORTANCE: A spinal cord tumor occurring in association with
      Klippel-Feil syndrome is quite rare. The removal of an anteriorly located spinal
      cord tumor at the level of block vertebrae creates a surgical challenge. CLINICAL
      PRESENTATION: A case of an intradural extramedullary dermoid cyst located
      anterior to the spinal cord and a syringomyelic cavity at the level of block
      vertebrae in a 43-year-old woman with Klippel-Feil syndrome is presented. She
      experienced pain and numbness in both shoulders and in her neck, and she had a
      slight weakness in both arms before the operation. Her weakness and the clinical
      symptoms completely disappeared after the operation, and the resolution of the
      syringomyelic cavity was observed at control magnetic resonance imaging.
      INTERVENTION: An anterior approach creating a fenestra corpectomy to the block
      vertebrae was performed, and the tumor was removed totally. No fusion or fixation
      was performed. CONCLUSION: To our knowledge, this is the first report of an
      anteriorly located intradural extramedullary cervical spine tumor in association
      with Klippel-Feil syndrome treated with this surgical technique. A three
      dimensional computed tomographic control scan obtained 1 year after the operation
      did not show any instability.

PMID- 14580294
TI  - The CyberKnife stereotactic radiosurgery system: description, installation, and
      an initial evaluation of use and functionality.

PMID- 14580295
TI  - A revealing Holter monitor.

PMID- 14580296
TI  - A chest x-ray image: total opacification of the hemithorax.
AB  - The authors describe a patient with a unilateral total lung opacification that
      was later resolved by bronchial lavage. Either a mechanical obstruction to the
      bronchus caused by endotracheal tube or mucous plug may be responsible for this
      chest x-ray image.

PMID- 14580297
TI  - Endovascular repair of accidental ligation of the right coronary artery during
      cardiorrhaphy for penetrating heart wound.
AB  - We report a patient with a cardiac penetrating wound who underwent cardiorrhaphy
      which resulted in accidental ligation of the proximal right coronary artery
      (RCA), producing a postoperative acute inferior wall myocardial infarction.
      Although the option of surgical relief of the suture over the RCA was discussed,
      a repeat operation was considered to be of very high risk. Therefore, an
      endovascular attempt to recanalize the vessel was chosen. The external
      constriction around the RCA was successfully relieved with percutaneous
      transluminal coronary angioplasty (PTCA) and stenting. To our knowledge, this
      particular situation has not yet previously been published.

PMID- 14580298
TI  - Hope for a better world.

PMID- 14580299
TI  - Correlations between preprocedure mood and clinical outcome in patients
      undergoing coronary angioplasty.
AB  - We studied the relationship between mood and mood shift immediately before
      percutaneous coronary intervention (PCI) and 3 end points: total ischemic burden
      during PCI, adverse cardiac end points (ACE) after PCI, and death by 6-month
      follow up. Patients (n = 119) with unstable angina or myocardial infarction
      completed a visual analog scale (VAS) twice before PCI; before and after a
      session of stress relaxation, imagery, or touch; or approximately 30 minutes
      apart for patients assigned to prayer or to standard care. VAS included
      happiness, satisfaction, calm, hope, worry, shortness of breath, fear, and
      sadness. We observed a significant correlation between higher hope score before
      PCI and lower ischemic burden. Patients who experienced ACE had significantly
      lower hope and happiness scores than those who did not. Patients who survived to
      6 months had significantly greater increases in worry and in hope. Our data
      suggest correlations between simple mood assessments before PCI and clinical
      outcomes during and after the procedure. More study is needed to understand
      whether attempts to alter patient mood can affect clinical outcomes.

PMID- 14580300
TI  - Type I primary hyperoxaluria: an unusual presentation of ventricular tachycardia.

PMID- 14580301
TI  - The hemodynamic signs of constrictive pericarditis can be mimicked by tricuspid
      regurgitation.
AB  - A case with clinical and hemodynamic findings consistent with constrictive
      pericarditis is reported. At surgery, the pericardium was not thickened or
      adherent to the epicardial wall. As suggested by echocardiography, a diagnosis of
      severe tricuspid regurgitation was confirmed. This case illustrates that invasive
      hemodynamic findings consistent with a picture of pericardial constriction can be
      produced by processes other than constrictive pericarditis.

PMID- 14580302
TI  - Fatal cardiac arrest following blunt chest trauma 17 years after a Senning
      operation.
AB  - Although frequent in patients who have undergone Senning or Mustard operations,
      cardiac arrhythmias after blunt chest trauma have not been reported. We report
      the case of a 17-year-old boy with ventricular fibrillation after a minor blow to
      the chest.

PMID- 14580303
TI  - Heart failure in women.
AB  - The incidence of congestive heart failure in the US population is increasing as
      more women and men survive with chronic hypertensive and atherosclerotic heart
      disease. Almost half the patients in the US with heart failure are women.
      Hypertension, diabetes mellitus, and cigarette smoking are all more potent risk
      factors for the development of heart failure in women than in men. Important
      differences in presentation and mortality explain gender differences in the
      clinical course of heart failure. Overall mortality is lower for women than for
      men with symptomatic heart failure. Some but not all of this difference can be
      explained by a lower rate of ischemic heart disease. Standard treatments for
      congestive heart failure, including angiotensin converting enzyme inhibitors and
      beta-blockers, have been shown to be equally efficacious in men and in women.
      Preliminary data on angiotensin II receptor blockers suggests equivalent benefit
      with further trial data awaited. Peripartum cardiomyopathy is a form of heart
      failure unique to women, occurring in the last stages of pregnancy or within 5
      months after delivery. Approximately half of affected women regain normal
      ventricular function but for those who do not, the risk of recurrent symptomatic
      heart failure and mortality during subsequent pregnancies is high.

PMID- 14580304
TI  - Oxidative stress, redox imbalance, and the aging process.

PMID- 14580306
TI  - Age-related increase in 4-hydroxynonenal adduction to rat heart alpha
      ketoglutarate dehydrogenase does not cause loss of its catalytic activity.
AB  - 4-hydroxynonenal (HNE), a product of omega-6 polyunsaturated fatty acid
      peroxidation, impairs mitochondrial respiration in vitro by adducting the alpha
      ketoglutarate dehydrogenase complex (KGDC) and inhibiting its activity. The
      present study seeks to define whether aging increases HNE adduction to rat heart
      KGDC, and whether such adduction impacts KGDC activity. We found that hearts from
      old rats exhibit significantly (p< or =0.01) higher HNE-modified mitochondrial
      proteins when compared with those from young rats. Among these proteins,
      dihydrolipoamide succinyltransferase, the E2k component of KGDC, was most
      markedly modified (p< or =0.01) by HNE with age. As opposed to that seen in
      vitro, no significant change in electrophoretic mobility or impairment in enzyme
      activity was observed. On the contrary, KGDC activity increased onefold (p< or
      =0.01) in old rats, suggesting that the aging myocardium is not affected by HNE
      adduction or compensates for such damage. Further analysis revealed that
      heightened KGDC activity was not due to increased protein content or gene
      expression, but correlates with a lower Km for alpha-ketoglutarate. Thus,
      contrary to that observed in vitro, the measurement of HNE-KGDC adduct in rat
      heart is more relevant as a marker of age-related protein oxidation than a factor
      of mitochondrial dysfunction.

PMID- 14580305
TI  - Iron accumulation during cellular senescence in human fibroblasts in vitro.
AB  - Iron accumulates as a function of age in several tissues in vivo and is
      associated with the pathology of numerous age-related diseases. The molecular
      basis of this change may be due to a loss of iron homeostasis at the cellular
      level. Therefore, changes in iron content in primary human fibroblast cells (IMR
      90) were studied in vitro as a model of cellular senescence. Total iron content
      increased exponentially during cellular senescence, resulting in 10-fold higher
      levels of iron compared with young cells. Low-dose hydrogen peroxide (H2O2)
      induced early senescence in IMR-90s and concomitantly accelerated iron
      accumulation. Furthermore, senescence-related and H2O2-stimulated iron
      accumulation was attenuated by N-tert-butylhydroxylamine (NtBHA), a mitochondrial
      antioxidant that delays senescence in vitro. However, SV40-transformed,
      immortalized IMR-90s showed no time-dependent changes in metal content in culture
      or when treated with H2O2 and/or NtBHA. These data indicate that iron
      accumulation occurs during normal cellular senescence in vitro. This accumulation
      of iron may contribute to the increased oxidative stress and cellular dysfunction
      seen in senescent cells.

PMID- 14580307
TI  - Decreased synthetic capacity underlies the age-associated decline in glutathione
      content in Fisher 344 rats.
AB  - Although it is well documented that the concentration of glutathione (GSH), the
      most abundant intracellular free thiol and an important antioxidant, declines
      with age in many tissues of different animal species, the underlying mechanism is
      not well understood. In a previous study, we showed that the expression of the
      glutamate cysteine ligase genes was down-regulated with age, accompanied by a
      decline in GSH content in the liver, kidney, and lung of Fisher 344 rats. The aim
      of this study was to examine the age-associated changes in the activities of
      three other enzymes, which also play important roles in GSH biosynthesis, to
      further explore the mechanism underlying the age-associated decline in GSH
      content in Fisher 344 rats. The results showed for the first time that the
      activity and gene expression of glutathione synthase, which catalyzes the second
      reaction in de novo GSH synthesis, were also decreased with increased age in the
      lung and kidney, but not in the liver or heart. No age-associated change in the
      activity of either gamma-glutamyltranspeptidase or glutathione reductase was
      observed in any of the organs examined. The results further indicate that
      decreased GSH synthetic capacity is responsible for the age-associated decline in
      GSH content in Fisher 344 rats.

PMID- 14580308
TI  - Role of redox imbalance in the molecular mechanisms responsible for
      immunosenescence.
AB  - The elderly suffer impairments to their immune system, evidenced by higher
      susceptibility to infections, cancer, and many diseases believed to be autoimmune
      in nature. A dysregulated overexpression of many proinflammatory cytokines also
      occurs with aging, as does the synthesis of enzymes that control expression of
      inflammatory lipid mediators and reactive oxygen species. An inappropriate
      activation of redox-controlled transcription factors, like nuclear factor-kappaB,
      occurs in many tissues from aged donors, and has been linked to excesses in
      cellular oxidative stress. Recently, the peroxisome proliferator-activated
      receptor-alpha (PPARalpha) has been evaluated for its effects on inflammatory and
      adaptive immune processes. PPARalpha provides redox-balancing influences on
      various lymphoid cell types and their inducible responses. We recently discovered
      that PPARalpha transiently suppresses the transcription of gamma-interferon
      (IFNgamma) by inhibiting the induction of T-bet. We now report that PPARalpha
      expression in CD4+ T cells is affected by the aging process. Lower PPARalpha
      levels are present in aged CD4+ T cells, and appear responsible for the
      suppressed interleukin-2 and exaggerated IFNgamma responses by these cells.
      Restoration of PPARalpha, T-bet, interleukin-2, and IFNgamma responses was found
      in T cells from aged animals supplemented with vitamin E, suggesting that
      interventions that focus on restoring redox balance might benefit the ailing aged
      immune system.

PMID- 14580309
TI  - Mitochondrial theory of aging: importance to explain why females live longer than
      males.
AB  - Females live longer than males in many species, including humans. This can be
      explained on the basis of the mitochondrial theory of aging. Mitochondria from
      females produce significantly less hydrogen peroxide than those from males and
      have higher levels of mitochondrial reduced glutathione, manganese superoxide
      dismutase, and glutathione peroxidase than males. Oxidative damage to
      mitochondrial DNA is also fourfold higher in males than in females. These
      differences may be explained by estrogens. Ovariectomy abolishes the gender
      differences between males and females and estrogen replacement rescues the
      ovariectomy effect. The challenge for the future is to find molecules that have
      the beneficial effects of estradiol, but without its feminizing effects.
      Phytoestrogens or phytoestrogen-related molecules may be good candidates to meet
      this challenge.

PMID- 14580310
TI  - The free radical theory of aging.
AB  - Aging is the accumulation of changes that increase the risk of death. Aging
      changes can be attributed to development, genetic defects, the environment,
      disease, and an inborn process: the aging process. The latter is the major risk
      factor for disease and death after age 28 in the developed countries. In these
      countries, average life expectancies at birth (ALE-B) now range from 76 to 79
      years, 6-9 years less than the limit of approximately 85 years imposed by aging.
      Aging changes may be caused by free radical reactions. The extensive studies
      based on this possibility hold promise that the ALE-B can be extended to >85
      years and the maximum life span increased.

PMID- 14580311
TI  - The role of thioredoxin in the aging process: involvement of oxidative stress.
AB  - Reactive oxygen species are produced by various stressors derived from internal
      and external sources, including endogenous metabolic activities. Glucose
      metabolism is one of the most primitive sources for energy production for most
      cells; however, it may at the same time yield hazardous oxidative stress via
      simultaneous oxidant production. The protective mechanism against oxidative
      stress is thus an indispensable biological function. Recently, genetic mutation
      loci affecting life span were isolated from experimental model organisms, and
      several locus products were found to be closely linked with machinery either
      producing or defending oxidative stress. Thioredoxin (TRX) is a small protein
      having strong antioxiradical quenching capabilities and other multiple functions
      depending on the cellular redox state. In this review, we focus on the role of
      TRX in the aging process (senescence) as a redox-regulating molecule against
      oxidative stress. We also discuss the possibility of the TRX system serving as an
      index marker for cellular proliferation and senescence.

PMID- 14580312
TI  - Oxidative stress and neuronal adaptation in Alzheimer disease: the role of SAPK
      pathways.
AB  - Recent evidence indicates that oxidative stress occurs early in the progression
      of Alzheimer disease, significantly before the development of the hallmark
      pathologies, namely neurofibrillary tangles and senile plaques. The interaction
      of abnormal mitochondria, redox transition metals, and oxidative stress response
      elements contributes to the generation of reactive oxygen species in diseased
      neurons. Oxidative damage to major cellular molecules is seen in a number of
      disease states that are either acute or chronic and it is apparent that without
      eliciting compensations that restore redox balance, cells will rapidly succumb to
      death. Indeed, although oxidative stress is a prominent feature in Alzheimer
      disease, few vulnerable neurons show clear signs of apoptosis, suggesting that
      the level of oxidative stress does not significantly exceed neuronal oxidative
      defenses. In light of this observation, we propose that neurons in Alzheimer
      disease are exposed to low, but chronic, levels of oxidative stress that lead
      neurons to elicit adaptive responses such as the activation of stress-activated
      protein kinase pathways.

PMID- 14580313
TI  - Oxidation of methionine residues of proteins: biological consequences.
AB  - Most reactive oxygen species (ROS) can oxidize methionine (Met) residues of
      proteins to methionine sulfoxide (MetO). However, unlike the ROS-dependent
      oxidation of other amino acid residues of proteins (except cysteine residues),
      the oxidation of Met residues is readily reversed by the action of methionine
      sulfoxide reductase (Msr) that catalyzes the thioredoxin-dependent reduction of
      MetO residues of proteins back to Met. We summarize here results of studies
      showing that the cyclic interconversion of Met and MetO residues of proteins is
      involved in several different biological processes: (a) It is the basis of an
      important antioxidant mechanism for the scavenging of ROS. (b) It is likely
      involved in the regulation of enzyme activities. (c) It is involved in cell
      signaling. (d) It can target proteins for proteolytic degradation. Furthermore, a
      loss in the ability to catalyze the reduction of protein MetO to Met residues
      leads to a decrease in the maximum life span, whereas overexpression of this
      activity leads to an increase in the life span of animals. In addition, a
      decrease in Msr activities in brain tissues is associated with the development of
      Alzheimer's disease.

PMID- 14580314
TI  - Programmed neuronal death.

PMID- 14580315
TI  - Bax, reactive oxygen, and cytochrome c release in neuronal apoptosis.
AB  - Half of all neurons produced during embryogenesis undergo apoptotic death shortly
      before birth or soon thereafter. Two cell culture models have been used
      extensively to investigate the cellular and molecular mechanisms underlying
      apoptosis during neuronal development: (a) sympathetic neurons deprived of their
      required neurotrophic factor, nerve growth factor, and (b) cerebellar granule
      neurons deprived of serum in low-potassium medium. A dramatic increase in
      mitochondrial-derived reactive oxygen species (ROS) occurs during the apoptotic
      death of both of these cell types. These ROS lie downstream from the proapoptotic
      protein, Bax. Bax normally resides in the cytoplasm, but translocates to the
      outer mitochondrial membrane during apoptosis. Once associated with mitochondria,
      Bax causes release of apoptogenic factors from the mitochondria into the
      cytoplasm, thus inducing or augmenting the apoptotic cascade. Although there is
      much controversy about the exact mechanism by which Bax causes release of these
      factors, recent evidence suggests that the Bax-induced ROS are critical for this
      release to occur in both sympathetic and cerebellar granule neurons. Because Bax
      is critical for the apoptotic death of many other types of neurons, it is likely
      that increased ROS is important for the death of these cells as well.

PMID- 14580316
TI  - Reactive oxygen radicals and pathogenesis of neuronal death after cerebral
      ischemia.
AB  - Reactive oxygen species have been implicated in brain injury after cerebral
      ischemia. These oxidants can damage proteins, lipids, and DNA, and lead to cell
      injury and necrosis. Oxidants are also initiators in intracellular cell death
      signaling pathways that may lead to apoptosis. The possible targets of this redox
      signaling include mitochondria, death membrane receptors, and DNA repair enzymes.
      Genetic manipulation of intrinsic antioxidants and the factors in the signaling
      pathways has provided substantial progress in understanding the mechanisms in
      cell death signaling pathways and involvement of oxygen radicals in ischemic
      brain injury. Future studies of these pathways may provide novel therapeutic
      strategies in clinical stroke.

PMID- 14580318
TI  - Antiapoptotic and pronecrotic actions of neurotrophins.
AB  - Neurotrophins promote the differentiation, growth, and survival of neurons in the
      nervous system. Specifically, neurotrophins promote neuronal survival by
      interfering with programmed cell death or apoptosis. In addition to roles of
      neurotrophins as survival factors, neurotrophins can act as risk factors of
      neuronal injury under various pathological conditions. Neurotrophins markedly
      potentiate neuronal cell necrosis induced by activation of N-methyl-D-aspartate
      receptors, deprivation of oxygen and glucose, and free radicals. Moreover,
      prolonged exposure to neurotrophins results in widespread neuronal necrosis
      through free radical-mediated mechanisms. Whereas cellular and molecular
      mechanisms underlying antiapoptosis action of neurotrophins have been well
      documented, extensive study will be needed to delineate mechanisms for the
      neurotrophin-induced neuronal necrosis through activation of Trk tyrosine kinase
      receptors.

PMID- 14580317
TI  - Role of proteolytic activation of protein kinase Cdelta in oxidative stress
      induced apoptosis.
AB  - Protein kinase Cdelta (PKCdelta), a member of the novel PKC family, is emerging
      as a redox-sensitive kinase in various cell types. Oxidative stress activates the
      PKCdelta kinase by translocation, tyrosine phosphorylation, or proteolysis.
      During proteolysis, caspase-3 cleaves the native PKCdelta (72-74 kDa) into 41-kDa
      catalytically active and 38-kDa regulatory fragments to persistently activate the
      kinase. The proteolytic activation of PKCdelta plays a key role in promoting
      apoptotic cell death in various cell types, including neuronal cells. Attenuation
      of PKCdelta proteolytic activation by antioxidants suggests that the cellular
      redox status can influence activation of the proapoptotic kinase. PKCdelta may
      also amplify apoptotic signaling via positive feedback activation of the caspase
      cascade. Thus, the dual role of PKCdelta as a mediator and amplifier of apoptosis
      may be important in the pathogenesis of major neurodegenerative disorders, such
      as Parkinson's disease, Alzheimer's disease, and Huntington disease.

PMID- 14580319
TI  - Amplification of a reactive oxygen species signal in axotomized retinal ganglion
      cells.
AB  - Retinal ganglion cells (RGCs) undergo apoptosis after axonal injury. Elucidation
      of the sequence of intracellular events proximal to caspase activation may allow
      development of effective neuroprotective strategies. In this study, we explored
      the role that reactive oxygen species may have in signaling RGC apoptosis after
      axonal injury. Using the fluorescent probe dihydroethidium, we were able to
      measure intracellular superoxide anion production. We found that axotomized RGCs
      exposed to oxidative stress exhibited a secondary superoxide burst. The broad
      spectrum caspase inhibitor Z-Val-Ala-DL-Asp-fluoromethyl ketone did not block the
      burst, suggesting it is proximal to caspase activation, but it was inhibited by
      cycloheximide, consistent with a requirement for protein synthesis. These results
      are consistent with RGC axotomy inducing synthesis of one or more proteins that
      mediate oxidative amplification. This could be an early event in signaling of RGC
      apoptosis after axonal injury.

PMID- 14580320
TI  - Prooxidant effects of NGF withdrawal and MEK inhibition in sympathetic neurons.
AB  - An increase of mitochondrial-derived reactive oxygen species (ROS) occurs in
      nerve growth factor (NGF)-deprived sympathetic neurons undergoing apoptotic
      death. It has been reported that NGF suppresses increased ROS production by the
      mitochondria in these cells through a mitogen-activated protein kinase kinase
      (MEK)/mitogen-activated protein (MAP) kinase pathway because NGF withdrawal
      inactivates this pathway and the MEK inhibitor, PD98059, increases ROS in the
      presence of NGF. We show here that treating rat sympathetic neurons in cell
      culture with PD98059 greatly decreased cellular concentrations of reduced
      glutathione (GSH), a major cellular antioxidant. Therefore, it is likely that
      this inhibitor induces a cellular prooxidant state in NGF-maintained sympathetic
      neurons primarily by decreasing GSH concentration rather than by causing
      increased mitochondrial ROS production. These data suggest that the MEK/MAP
      kinase signaling pathway regulates cellular GSH concentration.

PMID- 14580321
TI  - The effects of oxidative stress on mitochondrial transmembrane potential in
      retinal ganglion cells.
AB  - Retinal ganglion cells (RGCs) are central neurons that undergo apoptosis after
      axonal injury. As the relationship between mitochondrial and oxidative signaling
      of apoptosis in neuronal systems is unclear, we sought to achieve a better
      understanding of the interplay of these two pathways by investigating the effect
      of direct oxidative stress on mitochondrial membrane potential in cultured RGCs,
      as measured with the dual-emission probe JC-1. Treatment with hydrogen peroxide
      caused RGC mitochondrial depolarization. Several pharmacological treatments were
      used to define the mechanism. Whereas cycloheximide, tris(2
      carboxyethyl)phosphine, and cyclosporin A were unable to prevent the
      depolarization, bongkrekic acid significantly reduced the severity of the
      depolarization. This suggests that the hydrogen peroxide-induced depolarization
      may act through mitochondrial permeability transition pore opening independent of
      thiol oxidation, and may be preventable under certain conditions.

PMID- 14580322
TI  - Phospholipase A2, hydroxyl radicals, and lipid peroxidation in transient cerebral
      ischemia.
AB  - Phospholipid degradation is an important promoter of neuronal death after
      transient cerebral ischemia. Phospholipid hydrolysis by phospholipase A2 (PLA2)
      after transient cerebral ischemia releases arachidonic acid. Arachidonic acid
      metabolism results in formation of reactive oxygen species, lipid peroxides, and
      toxic aldehydes (malondialdehyde, 4-hydroxynonenal, and acrolein). Citicoline
      (cytidine-5'-diphosphocholine), an intermediate in phosphatidylcholine synthesis,
      has undergone 13 phase III clinical trials for stroke, and is being evaluated for
      treatment of Alzheimer's and Parkinson's diseases. Here we examined the effect of
      citicoline on PLA2 activity in relationship to attenuating hydroxyl radical (OH*)
      generation and lipid peroxidation after transient forebrain ischemia in gerbil.
      High Ca2+ dependency (millimolar range) of PLA2 activity suggests that secretory
      PLA2 is the predominant isoform in membrane and mitochondria. Citicoline
      attenuated the increase in PLA2 activity in both membrane and mitochondrial
      fractions. In vitro, citicoline and its components choline and cytidine had no
      effect on the PLA2 activity. Thus, citicoline is not a "direct PLA2 inhibitor."
      Citicoline also significantly attenuated loss of cardiolipin and arachidonic acid
      release from phosphatidylcholine and phosphatidylethanolamine. Transient cerebral
      ischemia resulted in significant formation of OH* and malondialdehyde, and
      citicoline significantly attenuated their formation. These results suggest that
      citicoline provides neuroprotection by attenuating the stimulation of PLA2.

PMID- 14580323
TI  - Formation of disulfide bond in p53 correlates with inhibition of DNA binding and
      tetramerization.
AB  - The p53 tumor suppressor protein is susceptible to oxidation, which prevents it
      from binding to its DNA response element. The goal of the current research was to
      determine the nature of the cysteine residue thiol oxidation that prevents p53
      from binding its DNA target and its effect on p53 structure. Recombinant p53,
      purified in the presence of the reducing agent dithiothreitol (DTT), contains
      five free thiol groups on the surface of the protein. In the absence of DTT, p53
      contains only four thiol groups, indicating that an average of one surface thiol
      group is readily susceptible to oxidation. Sulfite-mediated disulfide bond
      cleavage followed by reaction with 2-nitro-5-thiosulfobenzoate showed that
      oxidized p53 contains a single disulfide bond per monomer. By atomic force
      microscopy, we determined that reduced p53 binds to a double-stranded DNA
      containing the p53 promoter element of the MDM2 gene. The DNA-bound reduced p53
      has an average cross-sectional diameter of 8.61 nm and a height of 4.12 nm. The
      amount of oxidized p53 that bound to the promoter element was ninefold lower, and
      it has an 18% larger average cross-sectional diameter. Electromobility shift
      assays showed that binding of oxidized p53 to DNA was enhanced upon addition of
      DTT, indicating that oxidation is reversible. The possibility that oxidized p53
      contained significant amounts of sulfenic (-SOH), sulfinic (-SO2H), or sulfonic
      acid (-SO3H) was ruled out. Gel filtration chromatography indicated that
      oxidation increases the percentage of p53 monomers and high-molecular-weight
      oligomers (>1,000 kDa) relative to tetrameric p53. Protein modeling studies
      suggest that a mixed disulfide glutathione adduct on Cys182 could account for the
      observed stoichiometry of oxidized thiols and structural changes. The glutathione
      adduct may prevent proper helix-helix interaction within the DNA binding domain
      and contribute to tetramer dissociation.

PMID- 14580324
TI  - Sources for superoxide release: lessons from blockade of electron transport,
      NADPH oxidase, and anion channels in diaphragm.
AB  - Isolated diaphragm releases low levels of superoxide (O2*-) at rest and much
      higher levels during heat stress. The molecular source is unknown. The hypothesis
      was tested that heat stress stimulates mitochondrial complex activity or NADPH
      oxidases, resulting in increased O2*- release. The mitochondria within intact rat
      diaphragm were inhibited at complex I (amobarbital or rotenone) or complex I and
      II (rotenone plus thenoyltrifluoroacetone). NADPH oxidases were blocked by
      diphenyliodonium. None of these treatments inhibited O2*- release. Conversely,
      most blockers stimulated O2*- release. As intracellular O2*- generators require a
      mechanism for O2*- transport across the membrane, anion channel blockers,
      probenecid and 4,4'-diisothiocyanato-stilbene-2,2'-disulfonic acid, were also
      tested. Neither blocker had any inhibitory effect on O2*- release. These results
      suggest that O2*- released from diaphragm is not directly dependent on
      mitochondrial complex activity and that it is not a reflection of passive
      diffusion of O2*- through anion channels. Although the molecular source for
      extracellular O2*- remains elusive, it is clearly sensitive to temperature and
      conditions of "chemical hypoxia" induced by partial or complete mitochondrial
      inhibition.

PMID- 14580325
TI  - MnSOD up-regulates maspin tumor suppressor gene expression in human breast and
      prostate cancer cells.
AB  - Manganese superoxide dismutase (MnSOD) is an antioxidant enzyme with tumor
      suppressor activity; however, the molecular mechanisms of MnSOD antitumor effects
      remain unclear. We hypothesized that MnSOD activity in cancer cells might cause
      downstream changes in the expression of other tumor suppressor genes. To
      determine whether maspin, a tumor suppressor gene that inhibits breast cancer
      cell invasion and metastasis, might be a target of MnSOD, we forced MnSOD
      expression in several human breast and prostate cancer cell lines by adenovirus
      mediated gene transfer and measured maspin mRNA expression. Forced expression of
      MnSOD caused maspin mRNA to accumulate in a dose-dependent manner in both human
      breast and prostate cancer cells. Normal p53 was not necessary to mediate the
      effect of MnSOD because MnSOD up-regulated maspin in cells that harbor wild-type
      p53 and in cells that harbor mutant p53. Moreover, the effects of MnSOD on maspin
      were not due to demethylation of the maspin promoter. Analyses of maspin promoter
      activity, transcriptional run-on, and mRNA stability showed that maspin mRNA
      stability was the major mechanism for maspin up-regulation by MnSOD. Our findings
      identify a mechanism underlying MnSOD antitumor effects and provide evidence to
      support MnSOD as a genetic therapy in the treatment of human breast and prostate
      cancers.

PMID- 14580328
TI  - Adding facets to TNF signaling. The JNK angle.
AB  - In the October 3 issue of Cell, Deng et al. (2003) report that a JNK-dependent
      mitochondrial signal, the release of Smac/DIABLO, is required for TNF-induced
      caspase 8 activation and apoptosis. This process is interceded by a novel
      processed form of the BH3 only protein Bid.

PMID- 14580329
TI  - A role for rab7 GTPase in growth factor-regulated cell nutrition and apoptosis.
AB  - When growth factors are removed from many mammalian cells, growth ceases and
      apoptosis is induced. The small GTPase rab7, which regulates endocytic membrane
      traffic, participates in this process by mediating the regulated internalization
      and degradation of nutrient transporters. This process triggers nutrient
      starvation that helps to induce cell death.

PMID- 14580330
TI  - Aurora A on the mitotic spindle is activated by the way it holds its partner.
AB  - An exciting study in this issue reveals how binding of the microtubule associated
      protein TPX2 to the mitotic kinase Aurora A induces a conformational change. This
      moves the phosphorylated activation domain into a more compact position within
      the kinase core, providing a better substrate binding platform and hiding the
      activating phosphoryl group from attack by PP1.

PMID- 14580331
TI  - Better late than never for repair of miscoding lesions within a transcribed
      template.
AB  - Transcription does not always stall at base damage in DNA and can create mutated
      transcripts from miscoding lesions. In this issue of Molecular Cell, present
      genetic analysis of E. coli to indicate that the highly mutagenic purine
      modification, 8-oxoguanine, is subject to transcription-coupled repair despite
      transcriptional bypass and generation of mutant transcripts.

PMID- 14580332
TI  - Revised nomenclature for mammalian vacuolar-type H+ -ATPase subunit genes.
AB  - To date, the nomenclature of mammalian genes encoding the numerous subunits and
      their many isoforms that comprise the family of vacuolar H(+)-ATPases has not
      been systematic, resulting in confusion both in the literature and among
      investigators. We present the official new system for these genes, approved by
      both Human and Mouse Gene Nomenclature Committees.

PMID- 14580333
TI  - Crosstalk between LXR and toll-like receptor signaling mediates bacterial and
      viral antagonism of cholesterol metabolism.
AB  - The liver X receptors (LXR) alpha and beta are regulators of cholesterol
      metabolism and determinants of atherosclerosis susceptibility. Viral and
      bacterial pathogens have long been suspected to be modulators of atherogenesis;
      however, mechanisms linking innate immunity to cholesterol metabolism are poorly
      defined. We demonstrate here that pathogens interfere with macrophage cholesterol
      metabolism through inhibition of the LXR signaling pathway. Activation of Toll
      like receptors (TLR) 3 and 4 by microbial ligands blocks the induction of LXR
      target genes including ABCA1 in cultured macrophages as well as in aortic tissue
      in vivo. As a consequence of these transcriptional effects, TLR3/4 ligands
      strongly inhibit cholesterol efflux from macrophages. Crosstalk between LXR and
      TLR signaling is mediated by IRF3, a specific effector of TLR3/4 that inhibits
      the transcriptional activity of LXR on its target promoters. These findings
      highlight a common mechanism whereby bacterial and viral pathogens may modulate
      macrophage cholesterol metabolism and cardiovascular disease.

PMID- 14580334
TI  - Activin receptor-like kinase (ALK)1 is an antagonistic mediator of lateral
      TGFbeta/ALK5 signaling.
AB  - Transforming growth factor-beta (TGFbeta) regulates the activation state of the
      endothelium via two opposing type I receptor/Smad pathways. Activin receptor-like
      kinase-1 (ALK1) induces Smad1/5 phosphorylation, leading to an increase in
      endothelial cell proliferation and migration, while ALK5 promotes Smad2/3
      activation and inhibits both processes. Here, we report that ALK5 is important
      for TGFbeta/ALK1 signaling; endothelial cells lacking ALK5 are deficient in
      TGFbeta/ALK1-induced responses. More specifically, we show that ALK5 mediates a
      TGFbeta-dependent recruitment of ALK1 into a TGFbeta receptor complex and that
      the ALK5 kinase activity is required for optimal ALK1 activation. TGFbeta type II
      receptor is also required for ALK1 activation by TGFbeta. Interestingly, ALK1 not
      only induces a biological response opposite to that of ALK5 but also directly
      antagonizes ALK5/Smad signaling.

PMID- 14580335
TI  - CK2 Is a C-Terminal IkappaB Kinase Responsible for NF-kappaB Activation during
      the UV Response.
AB  - NF-kappaB is activated in response to proinflammatory stimuli, infections, and
      physical stress. While activation of NF-kappaB by many stimuli depends on the
      IkappaB kinase (IKK) complex, which phosphorylates IkappaBs at N-terminal sites,
      the mechanism of NF-kappaB activation by ultraviolet (UV) radiation remained
      enigmatic, as it is IKK independent. We now show that UV-induced NF-kappaB
      activation depends on phosphorylation of IkappaBalpha at a cluster of C-terminal
      sites that are recognized by CK2 (formerly casein kinase II). Furthermore, CK2
      activity toward IkappaB is UV inducible through a mechanism that depends on
      activation of p38 MAP kinase. Inhibition of this pathway prevents UV-induced
      IkappaBalpha degradation and increases UV-induced cell death. Thus, the p38-CK2
      NF-kappaB axis is an important component of the mammalian UV response.

PMID- 14580336
TI  - Merlin, the product of the Nf2 tumor suppressor gene, is an inhibitor of the p21
      activated kinase, Pak1.
AB  - The Nf2 tumor suppressor gene codes for merlin, a protein whose function has been
      elusive. We describe a novel interaction between merlin and p21-activated kinase
      1 (Pak1), which is dynamic and facilitated upon increased cellular confluence.
      Merlin inhibits the activation of Pak1, as the loss of merlin expression results
      in the inappropriate activation of Pak1 under conditions associated with low
      basal activity. Conversely, the overexpression of merlin in cells that display a
      high basal activity of Pak1 resulted in the inhibition of Pak1 activation. This
      inhibitory function of merlin is mediated through its binding to the Pak1 PBD and
      by inhibiting Pak1 recruitment to focal adhesions. This link provides a possible
      mechanism for the effect of loss of merlin expression in tumorigenesis.

PMID- 14580337
TI  - Structural basis of Aurora-A activation by TPX2 at the mitotic spindle.
AB  - Aurora-A is an oncogenic kinase essential for mitotic spindle assembly. It is
      activated by phosphorylation and by the microtubule-associated protein TPX2,
      which also localizes the kinase to spindle microtubules. We have uncovered the
      molecular mechanism of Aurora-A activation by determining crystal structures of
      its phosphorylated form both with and without a 43 residue long domain of TPX2
      that we identified as fully functional for kinase activation and protection from
      dephosphorylation. In the absence of TPX2, the Aurora-A activation segment is in
      an inactive conformation, with the crucial phosphothreonine exposed and
      accessible for deactivation. Binding of TPX2 triggers no global conformational
      changes in the kinase but pulls on the activation segment, swinging the
      phosphothreonine into a buried position and locking the active conformation. The
      recognition between Aurora-A and TPX2 resembles that between the cAPK catalytic
      core and its flanking regions, suggesting this molecular mechanism may be a
      recurring theme in kinase regulation.

PMID- 14580338
TI  - Structural basis for Arl1-dependent targeting of homodimeric GRIP domains to the
      Golgi apparatus.
AB  - Golgins are large coiled-coil proteins that play a role in Golgi structure and
      vesicle traffic. The Arf-like GTPase Arl1 regulates the translocation of GRIP
      domain-containing golgins to Golgi membranes. We report here the 1.7 A resolution
      structure of human Arl1-GTP in a complex with the GRIP domain of golgin-245. The
      structure reveals that the GRIP domain consists of an S-shaped arrangement of
      three helices. The domain forms a homodimer that binds two Arl1-GTPs using two
      helices from each monomer. The structure is consistent with golgin-245 forming
      parallel coiled-coils and suggests how Arl1-GTP/GRIP complexes interact with
      Golgi membranes via the N termini of Arl1-GTP and the C-terminal tails of the
      GRIP domains. In cells, bivalent association with Arl1-GTP would increase
      residence time of the golgins on Golgi membranes. Despite no conservation of
      sequence, topology, or even helical direction, several other effectors form
      similar interactions with small GTPases via a pair of alpha helices, suggesting a
      common structural basis for effector recognition.

PMID- 14580339
TI  - Nucleotide binding by the Mdm2 RING domain facilitates Arf-independent Mdm2
      nucleolar localization.
AB  - The RING domain of Mdm2 contains a conserved Walker A or P loop motif that is a
      characteristic of nucleotide binding proteins. We found that Mdm2 binds adenine
      containing nucleotides preferentially and that nucleotide binding leads to a
      conformational change in the Mdm2 C terminus. Although nucleotide binding is not
      required for Mdm2 E3 ubiquitin ligase activity, we show that nucleotide binding
      defective P loop mutants are impaired in p14(ARF)-independent nucleolar
      localization both in vivo and in vitro. Consistent with this, ATP-bound Mdm2 is
      preferentially localized to the nucleolus. Indeed, we identify a unique amino
      acid substitution in the P loop motif (K454A) that uncouples nucleolar
      localization and E3 ubiquitin ligase activity of Mdm2 and leads to upregulation
      of the E3 activity both in human cells and in Caenorhabditis elegans. We propose
      that nucleotide binding-facilitated nucleolar localization of Mdm2 is an
      evolutionarily conserved regulator of Mdm2 activity.

PMID- 14580340
TI  - Oncogenic Ras and Akt signaling contribute to glioblastoma formation by
      differential recruitment of existing mRNAs to polysomes.
AB  - In order to determine the global effects of oncogenic Ras and Akt signaling
      pathways on translational efficiencies, we compared the gene expression profiles
      of total cellular mRNA and mRNA associated with polysomes. We found that the
      immediate effect of Ras and Akt signaling blockade on transcription was
      relatively modest; however, the profile of mRNA associated with polysomes was
      substantially altered. These observations indicate that the immediate effect of
      Ras and Akt signaling regulates the recruitment of specific mRNAs to ribosomes to
      a far greater extent than they regulate the production of mRNAs by
      transcriptional effects. The mRNAs most affected are those encoding proteins that
      regulate growth, transcription regulation, cell to cell interactions, and
      morphology. These data support a model whereby Ras and Akt signaling primarily
      lead to cellular transformation by altering the transcriptome and producing a
      radical shift in the composition of mRNAs associated with actively translating
      polysomes.

PMID- 14580341
TI  - Cleavage of the A site mRNA codon during ribosome pausing provides a mechanism
      for translational quality control.
AB  - Cells employ many mechanisms to ensure quality control during protein
      biosynthesis. Here, we show that, during the pausing of a bacterial ribosome, the
      mRNA being translated is cleaved at a site within or immediately adjacent to the
      A site codon. The extent of this A site mRNA cleavage is correlated with the
      extent of ribosome pausing as assayed by tmRNA-mediated tagging of the nascent
      polypeptide. Cleavage does not require tmRNA, the ribosomal alarmone (p)ppGpp, or
      bacterial toxins such as RelE which have been shown to stimulate a similar
      activity. Translation is required for cleavage, suggesting that the ribosome
      participates in the reaction in some fashion. When normal protein synthesis is
      compromised, A site mRNA cleavage and the tmRNA system provide a mechanism for
      reducing translational errors and the production of aberrant and potentially
      harmful polypeptides.

PMID- 14580342
TI  - MazF cleaves cellular mRNAs specifically at ACA to block protein synthesis in
      Escherichia coli.
AB  - Escherichia coli contains operons called "addiction modules," encoding toxin and
      antitoxin, which are responsible for growth arrest and cell death. Here, we
      demonstrate that MazF toxin encoded by "mazEF addiction module" is a sequence
      specific (ACA) endoribonuclease functional only for single-stranded RNA. MazF
      works as a ribonuclease independent of ribosomes, and is, therefore, functionally
      distinct from RelE, another E. coli toxin, which assists mRNA cleavage at the A
      site on ribosomes. Upon induction, MazF cleaves whole cellular mRNAs to
      efficiently block protein synthesis. Purified MazF inhibited protein synthesis in
      both prokaryotic and eukaryotic cell-free systems. This inhibition was released
      by MazE, the labile antitoxin against MazF. Thus, MazF functions as a toxic
      endoribonuclease to interfere with the function of cellular mRNAs by cleaving
      them at specific sequences leading to rapid cell growth arrest and cell death.
      The role of such endoribonucleases may have broad implication in cell physiology
      under various growth conditions.

PMID- 14580343
TI  - Eukaryotic RNase P: role of RNA and protein subunits of a primordial catalytic
      ribonucleoprotein in RNA-based catalysis.
AB  - Ribonuclease P (RNase P) is an essential enzyme that processes the 5' leader
      sequence of precursor tRNA. Eubacterial RNase P is an RNA enzyme, while its
      eukaryotic counterpart acts as catalytic ribonucleoprotein, consisting of RNA and
      numerous protein subunits. To study the latter form, we reconstitute human RNase
      P activity, demonstrating that the subunits H1 RNA, Rpp21, and Rpp29 are
      sufficient for 5' cleavage of precursor tRNA. The reconstituted RNase P precisely
      delineates its cleavage sites in various substrates and hydrolyzes the
      phosphodiester bond. Rpp21 and Rpp29 facilitate catalysis by H1 RNA, which seems
      to require a phylogenetically conserved pseudoknot structure for function.
      Unexpectedly, Rpp29 forms a catalytic complex with M1 RNA of E. coli RNase P. The
      results uncover the core components of eukaryotic RNase P, reveal its
      evolutionary origin in translation, and provide a paradigm for studying RNA-based
      catalysis by other nuclear and nucleolar ribonucleoprotein enzymes.

PMID- 14580344
TI  - Differential interactions between a twin-arginine signal peptide and its
      translocase in Escherichia coli.
AB  - The twin-arginine translocation (Tat) machinery of the Escherichia coli inner
      membrane is dedicated to the export of proteins harboring a conserved SRRxFLK
      motif in their signal sequence. TatA, TatB, and TatC are the functionally
      essential constituents of the Tat machinery, but their precise function is
      unknown. Using site-specific crosslinking, we have analyzed interactions of the
      twin-arginine precursor preSufI with the Tat proteins upon targeting to inner
      membrane vesicles. TatA association is observed only in the presence of a
      transmembrane H(+) gradient. TatB is found in contact with the entire signal
      sequence and adjacent parts of mature SufI. Interaction of TatC with preSufI is,
      however, restricted to a discrete area around the consensus motif. The results
      reveal a hierarchy in targeting of a Tat substrate such that for the primary
      interaction, TatC is both necessary and sufficient while a subsequent association
      with TatB likely mediates transfer from TatC to the actual Tat pore.

PMID- 14580345
TI  - The mechanism by which DNA adenine methylase and PapI activate the pap epigenetic
      switch.
AB  - The expression of pyelonephritis-associated pili (Pap) in uropathogenic
      Escherichia coli is epigenetically controlled by a reversible OFF to ON switch.
      In phase OFF cells, the global regulator Lrp is bound to pap sites proximal to
      the pilin promoter, whereas in phase ON cells, Lrp is bound to promoter distal
      sites. We have found that the local regulator PapI increases the affinity of Lrp
      for the sequence "ACGATC," which contains the target "GATC" site for DNA adenine
      methylase (Dam) and is present in both promoter proximal and distal sites.
      Mutational analyses show that methylation of the promoter proximal GATC(prox)
      site by Dam is required for transition to the phase ON state by specifically
      blocking PapI-dependent binding of Lrp to promoter proximal sites. Furthermore,
      our data support the hypothesis that PapI-dependent binding of Lrp to a
      hemimethylated GATC(dist) site generated by DNA replication is a critical
      component of the switch mechanism.

PMID- 14580346
TI  - Transcriptional mutagenesis induced by uracil and 8-oxoguanine in Escherichia
      coli.
AB  - Cells exposed to DNA damaging agents in their natural environment do not undergo
      continuous cycles of replication but are more frequently engaged in gene
      transcription. Luciferase gene expression analysis with DNA templates containing
      uracil or 8-oxoguanine, placed at a defined position, indicated that in
      nondividing Escherichia coli cells, efficient mutagenic lesion bypass does occur
      in vivo during transcription. Sequence analyses of the transcript population
      revealed that RNA polymerase inserts adenine opposite to uracil, and adenine or
      cytosine opposite to 8-oxoguanine. Surprisingly, deletions were also detected for
      8-oxoguanine-containing templates, indicating RNA polymerase slippage over this
      lesion. Genetic analyses showed that, in E. coli, 8-oxoguanine is subject to
      transcription-coupled repair. Consequently, DNA damages alter transcription
      fidelity in vivo, which may lead to the production of mutant proteins that have
      the potential to change the phenotype of nondividing cells.

PMID- 14580347
TI  - Inhibition of P-TEFb (CDK9/Cyclin T) kinase and RNA polymerase II transcription
      by the coordinated actions of HEXIM1 and 7SK snRNA.
AB  - The positive transcriptional elongation factor b (P-TEFb), consisting of CDK9 and
      cyclin T, stimulates transcription by phosphorylating RNA polymerase II. It
      becomes inactivated when associated with the abundant 7SK snRNA. Here, we show
      that the 7SK binding alone was not sufficient to inhibit P-TEFb. P-TEFb was
      inhibited by the HEXIM1 protein in a process that specifically required 7SK for
      mediating the HEXIM1:P-TEFb interaction. This allowed HEXIM1 to inhibit
      transcription both in vivo and in vitro. P-TEFb dissociated from HEXIM1 and 7SK
      in cells undergoing stress response, increasing the level of active P-TEFb for
      stress-induced transcription. P-TEFb was the predominant HEXIM1-associated
      protein factor, and thus likely to be the principal target of inhibition
      coordinated by HEXIM1 and 7SK. Since HEXIM1 expression is induced in cells
      treated with hexamethylene bisacetamide, a potent inducer of cell
      differentiation, targeting the general transcription factor P-TEFb by HEXIM1/7SK
      may contribute to the global control of cell growth and differentiation.

PMID- 14580348
TI  - Targeting activity is required for SWI/SNF function in vivo and is accomplished
      through two partially redundant activator-interaction domains.
AB  - The SWI/SNF complex is required for the expression of many yeast genes. Previous
      studies have implicated DNA binding transcription activators in targeting SWI/SNF
      to UASs and promoters. To determine how activators interact with the complex and
      to examine the importance of these interactions, relative to other potential
      targeting mechanisms, for SWI/SNF function, we sought to identify and mutate the
      activator-interaction domains in the complex. Here we show that the N-terminal
      domain of Snf5 and the second quarter of Swi1 are sites of activation domain
      contact. Deletion of both of these domains left the SWI/SNF complex intact but
      impaired its ability to bind activation domains. Importantly, while deletion of
      either domain alone had minor phenotypic effect, deletion of both resulted in
      strong SWI/SNF related phenotypes. Thus, two distinct activator-interaction
      domains play overlapping roles in the targeting activity of SWI/SNF, which is
      essential for its function in vivo.

PMID- 14580349
TI  - The TBN protein, which is essential for early embryonic mouse development, is an
      inducible TAFII implicated in adipogenesis.
AB  - Human TFIID contains the TATA-binding protein (TBP) and several TBP-associated
      factors (hTAFs) that have been shown to play important roles, within TFIID, both
      in core promoter recognition and as coactivators. Here we show that the human
      TAF(II)43 (TAF8) is an integral component of a functional TFIID and an apparent
      ortholog to the recently reported mouse TBN, which is essential for early
      embryonic mouse developmental events. Significantly, we also show that TAF8 is
      dramatically induced and sequestered within TFIID upon differentiation of 3T3-L1
      preadipocytes to adipocytes, whereas the expression of all other TAFs tested is
      slightly reduced. Moreover, when ectopically expressed, the histone fold domain
      of TAF8 acts as a dominant-negative mutant and selectively inhibits 3T3-L1
      adipogenic differentiation. Furthermore TAF8 acts as a positive regulator of
      adipogenesis and reverses the inhibitory effect of its histone fold. These data
      suggest a selective role for TAF8 in a specific cell differentiation process(es).

PMID- 14580350
TI  - RNA polymerase II/TFIIF structure and conserved organization of the initiation
      complex.
AB  - The structure of an RNA polymerase II/general transcription factor TFIIF complex
      was determined by cryo-electron microscopy and single particle analysis. Density
      due to TFIIF was not concentrated in one area but rather was widely distributed
      across the surface of the polymerase. The largest subunit of TFIIF interacted
      with the dissociable Rpb4/Rpb7 polymerase subunit complex and with the mobile
      "clamp." The distribution of the second largest subunit of TFIIF was very similar
      to that previously reported for the sigma subunit in the bacterial RNA polymerase
      holoenzyme, consisting of a series of globular domains extending along the
      polymerase active site cleft. This result indicates that the second TFIIF subunit
      is a true structural homolog of the bacterial sigma factor and reveals an
      important similarity of the transcription initiation mechanism between bacteria
      and eukaryotes. The structure of the RNAPII/TFIIF complex suggests a model for
      the organization of a minimal transcription initiation complex.

PMID- 14580351
TI  - p53 functions through stress- and promoter-specific recruitment of transcription
      initiation components before and after DNA damage.
AB  - The tumor suppressor protein p53 regulates transcriptional programs that control
      the response to cellular stress. We show that distinct mechanisms exist to
      activate p53 target genes as revealed by marked differences in affinities and
      damage-specific recruitment of transcription initiation components. p53 functions
      in a temporal manner to regulate promoter activity both before and after stress.
      Before DNA damage, basal levels of p53 are required to assemble a poised RNA
      polymerase II initiation complex on the p21 promoter. RNA pol II is converted
      into an elongating form shortly after stress but before p53 stabilization.
      Proapoptotic promoters, such as Fas/APO1, have low levels of bound RNA pol II but
      undergo damage-induced activation through efficient reinitiation. Surprisingly,
      in a p53-dependent process key basal factors TAFII250 and TFIIB assemble into the
      transcription machinery in a stress- and promoter-specific manner, behaving as
      differential cofactors for p53 action after distinct types of DNA damage.

PMID- 14580352
TI  - Dynamic control of Rad51 recombinase by self-association and interaction with
      BRCA2.
AB  - Here, we visualize GFP-Rad51 fusion proteins in the nucleus of living cells to
      demonstrate the dynamic compartmentalization of Rad51 by self-association or by
      binding to BRCA2. Mutants of Rad51 that fail to oligomerize and/or to bind BRCA2
      distinguish three fractions of Rad51 within the nucleoplasm: a relatively mobile
      fraction, an immobile oligomerized fraction, and an immobile BRCA2-bound
      fraction. Strikingly, inhibition of replication by hydroxyurea reduces the
      immobile fraction of nucleoplasmic Rad51. This effect is specific to Rad51
      mutants that retain the capacity to bind BRCA2, indicating that the BRCA2-bound
      fraction is selectively mobilized. We propose that arrested replication triggers
      a switch between dual functions of BRCA2 in sequestering or mobilizing a small
      fraction of nucleoplasmic Rad51 and suggest a mechanism for the dynamic control
      of protein complexes that participate in homologous recombination.

PMID- 14580353
TI  - The BRCA2-interacting protein DSS1 is vital for DNA repair, recombination, and
      genome stability in Ustilago maydis.
AB  - DSS1 encodes a small acidic protein shown in recent structural studies to
      interact with the DNA binding domain of BRCA2. Here we report that an ortholog of
      DSS1 is present in Ustilago maydis and associates with Brh2, the BRCA2-related
      protein, thus recapitulating the protein partnership in this genetically amenable
      fungus. Mutants of U. maydis deleted of DSS1 are extremely radiation sensitive,
      deficient in recombination, defective in meiosis, and disturbed in genome
      stability; these phenotypes mirror previous observations of U. maydis mutants
      deficient in Brh2 or Rad51. These findings conclusively show that Dss1
      constitutes a protein with a significant role in the recombinational repair
      pathway in U. maydis, and imply that it plays a similar key role in the
      recombination systems of organisms in which recombinational repair is BRCA2
      dependent.

PMID- 14580354
TI  - Photo-induced peptide cleavage in the green-to-red conversion of a fluorescent
      protein.
AB  - Green fluorescent protein from the jellyfish (Aequorea GFP) and GFP-like proteins
      from coral species encode light-absorbing chromophores within their protein
      sequences. A coral fluorescent protein, Kaede, contains a tripeptide, His(62)
      Tyr(63)-Gly(64), which acts as a green chromophore that is photoconverted to red.
      Here, we present the structural basis for the green-to-red photoconversion. As in
      Aequorea GFP, a chromophore, 4-(p-hydroxybenzylidene)-5-imidazolinone, derived
      from the tripeptide mediates green fluorescence in Kaede. UV irradiation causes
      an unconventional cleavage within Kaede protein between the amide nitrogen and
      the alpha carbon (Calpha) at His(62) via a formal beta-elimination reaction,
      which requires the whole, intact protein for its catalysis. The subsequent
      formation of a double bond between His(62)-Calpha and -Cbeta extends the pi
      conjugation to the imidazole ring of His(62), creating a new red-emitting
      chromophore, 2-[(1E)-2-(5-imidazolyl)ethenyl]-4-(p-hydroxybenzylidene)-5
      imidazolinone. The present study not only reveals diversity in the chemical
      structure of fluorescent proteins but also adds a new dimension to
      posttranslational modification mechanisms.

PMID- 14580355
TI  - Ultrastructure of developing tooth plates in the Australian lungfish,
      Neoceratodus forsteri (Osteichthyes: Dipnoi).
AB  - While the lungfish dentition is partially understood as far as morphology and
      light microscopic structure is concerned, the ultrastructure is not. Each tooth
      plate is associated with a dental lamina that develops from the inner layer of
      endodermal cells that form the oral epithelium. Dentines, bone and cartilage of
      the jaws differentiate from mesenchyme cells aggregating beneath the oral
      endothelium. Enamel, in the developing and in the mature form, has similarities
      to that of other early vertebrates, but unusual characters appear as development
      proceeds. Ameloblasts are capable of secreting enamel, and, with mononuclear
      osteoclasts, of remodelling the bone below the tooth plate. The forms of dentine,
      all based largely on an extracellular matrix of collagen and mineralised with
      biological apatite, differ from each other and from the underlying bone in the
      ultrastructure of associated cells and in the mineralised extracellular matrices
      produced. Cell processes emerging from the odontoblasts and from the osteoblasts
      vary in length, degree of branching and of anastomoses between the processes,
      although all of the cell types have large amounts of rough endoplasmic reticulum.
      Mineralisation of the extracellular matrices varies among the enamel, dentines
      and bone in the tooth plate. In addition, the development of the hard tissues of
      the tooth plates indicates that many of the similarities in fine structure of the
      dentition in lungfish, to tissues in other fish and amphibia, apparent early in
      development, disappear as the dentition matures.

PMID- 14580356
TI  - Ultrastructure of ceramic-bone interface using hydroxyapatite and beta-tricalcium
      phosphate ceramics and replacement mechanism of beta-tricalcium phosphate in
      bone.
AB  - Hydroxyapatite (HA) and beta-tricalcium phosphate (beta-TCP) are useful for
      grafting and augmentation of bone tissue. Observation by transmission electron
      microscopy (TEM) was done to investigate the ultrastructures at the interfaces
      between the biomaterials and the adjacent tissue, and osteogenesis around the
      biomaterials in the present study. HA and beta-TCP ceramics were used in disk
      forms which had macropores and micropores, and were implanted between the
      parietal bone and the cranial periosteum of rats. Specimens were prepared for
      observation at 4 and 8 weeks postoperatively. The microscopic results indicated
      that an intervening layer was present on the surface of HA, whereas it was not
      present on the surface of beta-TCP. A characteristic fibrillar structure was
      observed in the intervening layer between HA and bone under decalcification by
      HCl. In beta-TCP, in reticular structures observed close to the bone tissue by
      optical microscopy, calcification and sparse collagen fibers were interspersed
      among the granules of beta-TCP. In addition, close to the interface between beta
      TCP and bone, many osteocytes with numerous processes were present. Some
      processes were elongated towards the interface. These results revealed the
      difference in the ultrastructures of the interfaces between HA and beta-TCP, and
      the dissolution mechanism of beta-TCP in bone.

PMID- 14580357
TI  - Spermiogenesis and sperm ultrastructure in Cichla intermedia with some
      considerations about Labroidei spermatozoa (Teleostei, Perciformes, Cichlidae).
AB  - Spermiogenesis and spermatozoal structure were studied in Cichla intermedia, a
      primitive species of Neotropical Cichlids. The analysis shows that spermiogenesis
      is characterized by chromatin compaction, flagellum development, nuclear
      rotation, nuclear fossa formation and residual cytoplasm elimination. In the
      spermatozoa, the head is round, the nucleus contains highly condensed filamentous
      clusters of chromatin and an acrosome is absent. The nuclear fossa is slightly
      eccentric and shows a projection that penetrates into the nuclear outline. The
      proximal centriole is located in the initial segment of the nuclear fossa. The
      midpiece and the cytoplasmic channel are long. The mitochondria, about 10 in
      number, are round or slightly elongated, disposed in two layers around the
      initial segment of the flagellum. The flagellum has a classical 9+2 axoneme and
      two lateral fins. The data available show that no characteristics of
      spermiogenesis or spermatozoa are exclusively found in members of the suborder
      Labroidei. However, three characteristics seem to be exclusively observed in
      Cichlidae: (1) compact filamentous clusters of chromatin; (2) slightly eccentric
      nuclear fossa; and, (3) number of mitochondria.

PMID- 14580358
TI  - Structure, histochemistry, and ultrastructure of the epithelium and stroma in the
      gerbil (Meriones unguiculatus) female prostate.
AB  - The female prostate has aroused scientific interest because it is subjected to
      the same diseases compromising the male prostate during aging. The objective of
      this work was to characterize structurally, cytochemically, and ultrastructurally
      the tissue compartments of the normal adult female prostate of Meriones
      unguiculatus gerbils. The morphological analyses showed that the gerbil's female
      prostate is constituted of a cluster of glands and ducts inserted in a
      musculofibrous stroma. The alveolar epithelium is differentiated and consisted of
      basal proliferating cells, intermediary cells, and secretory cells. The secretory
      cells are the most numerous cell type and continuously secrete glycoproteins. The
      basal cells are the source of the secretory cells and they are then responsible
      for the alveolus renovation. The prostatic stroma is abundant and rich in elastic
      and collagen fibers, which are closely associated with smooth muscle cells and
      fibroblasts. The results showed that the gerbil's female prostate shows
      morphological and ultrastructural homology to the human female prostate (Skene's
      gland), and despite being a small organ, it is a mature and physiologically
      active gland.

PMID- 14580359
TI  - Gamma radiation inhibits fibroblast-mediated collagen gel retraction.
AB  - Radiation exposure is known to impair healing in irradiated areas. Fibroblasts
      play a major role in the production and modification of extracellular matrix in
      wound repair. Since one important aspect of wound repair is the contraction of
      the wound, this study investigated the effects of radiation on the ability of
      fibroblasts to mediate collagen gel contraction in an in vitro model of wound
      retraction. After irradiation, the cells were detached and suspended in a
      solution of rat tail tendon collagen. Radiation exposure decreased retraction,
      and this effect was dose dependent. In order to define the mechanism of reduced
      gel retraction, we investigated alpha2beta1 cell surface integrin and
      fibronectin, which are thought to mediate contraction, and prostaglandin E2
      (PGE2), which is known to inhibit this process. PGE2 release increased dose
      responsively following radiation. The cyclooxygenase inhibitor indomethacin could
      partially restore the contractile activity of irradiated fibroblasts. Fibronectin
      production in gel culture showed a significant decrease. In contrast, there was
      no decrease in alpha2beta1 integrin expression in radiated cells. In conclusion,
      radiation decreases fibroblast-mediated gel contraction. Increased PGE2
      production and decreased fibronectin production by irradiated fibroblasts may
      contribute to this effect and may be in part responsible for poor healing of
      radiated tissue.

PMID- 14580360
TI  - Modulation of mThy28 nuclear protein expression during thymocyte development.
AB  - We have recently shown that down-regulation of mouse Thy28 (mThy28) protein
      expression appears to be accompanied by apoptotic processes. Thymocytes from mice
      contain moderate amounts of mThy28 protein and undergo proliferation,
      differentiation, or apoptosis during murine thymic maturation. As a first step to
      examine the potential role of the mThy28 protein in the thymocyte development,
      such as positive-negative selection, the expression of mThy28 protein in the
      thymocyte subsets was examined. Thymocytes are separated into four subpopulations
      by the expression levels of CD4 and CD8: CD4-CD8- (DN), CD4+CD8+ (DP), and
      CD4+CD8- or CD4-CD8+ (SP). Flow cytometry analysis using three-color staining
      demonstrated that the mThy28 expression in immature DP cells is lower than that
      in DN and SP cells. The down-regulation of the mThy28 expression in the DP stage
      was also detected by Western blotting and reverse transcription-polymerase chain
      reaction (RT-PCR). The immunostaining method also showed that mThy28 protein was
      expressed in the medulla containing mature thymocytes, but not the cortex having
      immature thymocytes. The mThy28 protein in the thymocytes was mainly localized in
      the nucleus, as recently demonstrated in lymphoma cells, indicating that the
      mThy28 protein resides in the nucleus, irrespective of the cyclic or resting
      stage of the cell cycle. Together, the observation that mThy28 expression is down
      modulated during the DP stage suggests that mThy28 protein might play some role
      in the positive-negative selection step in thymic maturation.

PMID- 14580361
TI  - Serotonin in the nervous system of the head region of the land planarian Bipalium
      kewense.
AB  - The presence and distribution of serotonin (5-hydroxytryptamine, or 5-HT) in the
      head region of the land planarian Bipalium kewense has been investigated by an
      indirect immunofluorescence technique combined with confocal scanning laser
      microscopy (CSLM), and also by immunogold labeling at ultrastructural level.
      Serotonin immunoreactivity (IR) was restricted to elements of the nervous system,
      such as the cerebral ganglion, and the peripheral nerve net. Most of 5-HT
      immunoreactive neurons are at the periphery of the brain; they were identified as
      unipolar, bipolar, and multipolar neurons. The ultrastructural results using
      immunogold labeling confirm the location of 5-HT within electron-dense vesicles
      (50-120 nm in diameter), clustered both in the cell bodies and in their
      processes. The intense 5-HT-IR herein demonstrated for B. kewense adds new data
      to the poorly studied nervous system of land planarians.

PMID- 14580362
TI  - Degradation of specific polyunsaturated fatty acids in red blood cells stored at 
      20 degrees C proceeds faster in patients with schizophrenia when compared with
      healthy controls.
AB  - Deficits in red blood cell (RBC) polyunsaturated fatty acids (PUFAs) have been
      extensively reported in schizophrenia although reports are inconsistent. A
      possible explanation for this inconsistency is varying storage conditions of
      blood samples prior to analysis, especially freezer storage temperature. We
      conducted a prospective investigation of fatty acid degradation rates in RBCs
      from healthy control subjects when samples from each individual were stored at
      both -20 degrees C or -70 degrees C. Differences were detected between storage
      conditions. A second prospective study was conducted to investigate the effect of
      differential storage conditions on RBC membrane fatty acids from schizophrenic
      patients. We found that storage at -20 degrees C was associated with reduced
      levels of PUFAs. Comparison of decay rates suggest that schizophrenics decay
      approximately twice as rapidly as controls. Furthermore, this phenomenon appears
      to be specific for the longer chain PUFAs suggesting that an enzymatic process
      may be responsible, e.g. elevated phospholipase A(2) activity, as opposed to
      simple chemical oxidation.

PMID- 14580363
TI  - Regulation of the human thromboxane A2 receptor gene in human megakaryoblastic
      MEG-01 cells.
AB  - Thromboxane A(2) (TXA(2)) is an important mediator for platelet aggregation and
      blood vessel constriction. TXA(2) receptor (TP receptor) is expressed in
      different cell types including smooth muscle cells, endothelial cells and
      platelets. Expression level of TP receptor may modulate the action of TXA(2) on
      target cells. In megakaryoblastic MEG-01 cells, a cell line representing a model
      for platelet precursor cells, addition of phorbolester 12-O-tetradecanoylphorbol
      13-acetate (TPA) caused an increase in transcriptional activity of TP receptor
      gene promoter. Within 20 h a rise in expression of TP receptor mRNA and protein
      was observed. The effect of TPA was concentration-dependent and was blocked by
      specific inhibitors of protein kinase C. Flow cytometry analysis indicated that
      the increase in TP receptor expression appeared to be one of the earliest events
      in the course of TPA-induced maturation of MEG-01 cells. Stimulation of the
      protein kinase A pathway by incubation with forskolin or IBMX caused a decrease
      in transcriptional activity. Promoter deletion experiments indicated that the
      responsive elements for protein kinase A and C are located upstream and
      downstream, respectively, of -700 bp of the TP receptor gene. These experiments
      indicate that the expression of the human thromboxane receptor is differently
      regulated in platelet precursor cells by the protein kinase A and C pathway.

PMID- 14580364
TI  - Expression of prostanoid receptors in human lower segment pregnant myometrium.
AB  - Prostanoids, especially prostaglandin (PG) E(2), are important mediators of
      uterine relaxation and contractions during gestation and parturition. Inhibitors
      of PG formation as well as PG analogues are used to modulate uterine tonus. So
      far, only limited data are available regarding the expression of prostanoid
      receptors in human pregnant myometrium. In the present study, the expression of
      the receptors for PGE(2) (EP1, EP2, EP3, EP4), PGF(2alpha) (FP), prostacyclin
      (IP), and thromboxane A(2) (TP) in human pregnant myometrium was studied by RT
      PCR, in situ hybridization and immunohistochemistry. Myometrial tissue was
      obtained from five women at term and not in labour and from two women who
      delivered preterm. Tissue specimens were excised from the upper edge of the
      transverse lower uterine segment incision. In all tissues analysed, EP1, EP2,
      EP3, EP4, FP, TP and IP receptor mRNA and protein was detected. mRNA expression
      for PGD(2) (DP) receptor was not detected in the majority of tissue specimens.
      EP1, EP2, EP4, IP, TP and FP receptor protein was detected on myometrial smooth
      muscle cells, whereas EP3 receptor protein was only expressed by stromal and
      endothelial cells. In situ hybridization experiments yielded similar results. The
      expression of the EP2 receptor mRNA was inversely related to gestational age. We
      suggest that the contractile effect of PGE(2) at term is probably mediated
      directly by the EP1 receptor expressed in myometrial smooth muscle cells and
      indirectly by the EP3 receptor expressed in stromal cells and a decrease in EP2
      receptor expression.

PMID- 14580365
TI  - Prostaglandin E2 stimulates sodium reabsorption in MDCK C7 cells, a renal
      collecting duct principal cell model.
AB  - We examined the direct epithelial effects of the major product of arachidonic
      acid metabolism in the kidney, prostaglandin E(2) (PGE(2)), on ion transport and
      signal transduction in the hormone-sensitive Madin-Darby canine kidney (MDCK) C7
      subclone as a model of renal collecting duct principal cells. MDCK C7 cells were
      grown on microporous permeable filter supports and mounted in Ussing-type
      chambers. Reverse transcriptase (RT)-PCR and sequencing were used to determine E
      prostanoid (EP) receptor expression. Basolateral and, about 14-fold less potent,
      apical addition of PGE(2) increased short-circuit current (I(sc)) in a
      concentration-dependent manner. This ion transport was biphasic with a rapid peak
      not detectable under chloride-free conditions. The remaining, stably elevated
      current was unaffected by furosemide, hydrochlorothiazide, ethylisopropanol
      amiloride, and 5-nitro-2-(3-phenyl-propyl-amino)benzoic acid (NPPB). In contrast,
      apical amiloride (10 microM) significantly decreased I(sc), indicating sodium
      reabsorption. The effect of PGE(2) was attenuated in the presence of vasopressin.
      Agonists acting by cAMP elevation like dibutyryl-cAMP and theophylline also
      induced an amiloride-sensitive ion transport with similar kinetics as PGE(2).
      Moreover, PGE(2) rapidly increased intracellular cAMP levels. RT-PCR demonstrated
      mRNA expression of the epithelial sodium channel (ENaC), and of the EP2 receptor
      in MDCK C7 cells. Accordingly, EP2 receptor agonist butaprost mimicked PGE(2)
      epithelial action. In conclusion, PGE(2) induces amiloride-sensitive sodium
      reabsorption in MDCK C7 monolayers. This ion transport is most likely mediated by
      EP2 receptor activation leading to increased intracellular cAMP levels.
      Therefore, PGE(2) might also contribute to Na(+) reabsorption in the mammalian
      collecting duct.

PMID- 14580366
TI  - Effect of 15-deoxy-delta12,14-prostaglandin J2 on IL-1beta-induced expression of
      epithelial neutrophil-activating protein-78 in human endothelial cells.
AB  - Epithelial neutrophil-activating peptide-78 (ENA-78) is a member of CXC
      chemokines. It is produced by endothelial cells stimulated with interleukin-1 (IL
      1), along with other CXC chemokines such as IL-8 and growth-related oncogene
      protein-alpha (GRO-alpha). IL-1-induced ENA-78 production by endothelial cells
      may be important for the regulation of neutrophil activation. 15-Deoxy
      Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) is a natural ligand for peroxisome
      proliferator-activated receptor-gamma (PPAR-gamma) and affects the expression of
      various genes. We examined the effect of 15d-PGJ(2) on the expression of ENA-78
      in cultured endothelial cells stimulated with IL-1beta. 15d-PGJ(2) inhibited the
      IL-1beta-induced expression of ENA-78, but not the expression of IL-8 or GRO
      alpha in response to IL-1. Ciglitazone, another agonist for PPAR-gamma, had no
      effect on the expression of ENA-78, suggesting that 15d-PGJ(2) may inhibit the
      expression of ENA-78 in a PPAR-gamma-independent manner. 15d-PGJ(2) may modulate
      inflammatory reactions by regulating the balance of CXC chemokines in endothelial
      cells.

PMID- 14580367
TI  - Cyclooxygenase 2 (COX2)-prostanoid pathway and liver diseases.
AB  - Cycloocygenases 2 (COX2)-prostanoid pathway plays important and complex roles in
      the pathogenesis of various liver diseases. Most studies indicated that COX2
      prostanoid pathway might suppress hepatic fibrogenesis by decreasing
      proliferation, migration, and contractility of hepatic stellate cells (HSCs). In
      animal model, COX2-prostanoid pathway increases portal hypertension, which can be
      reduced by treatment with COX2 inhibitor. In cirrhosis, COX2-prostanoid pathway
      may reduce formation of ascites by enhancing free water excretion, and protect
      gastric mucosa from ulcerative insults. Aberrant expression of COX2 has been well
      associated with hepatocarcinogenesis. COX2 inhibitors can effectively suppress
      proliferation of hepatocellular carcinoma (HCC) cells. This provided rationale
      for further testing COX2 inhibitors as clinical agents for HCC chemoprovention.
      Further studies will be needed to examine how COX2 inhibitors affect pathogenesis
      of various liver diseases.

PMID- 14580368
TI  - COX-3 the enzyme and the concept: steps towards highly specialized pathways and
      precision therapeutics?
AB  - Cyclooxygenases (COXs) catalyse the key rate-limiting step in prostanoid and
      thromboxane biosynthesis and are targets of non-steroidal anti-inflammatory drugs
      (NSAIDs). Until recently, the presence of only two isoforms-COX-1 and COX-2
      remained in question because the potent anti-pyretic and analgesic effects of
      acetaminophen (paracetamol, tylenol ben-u-ron) could not be explained by either
      COX-1 or COX-2 blockades. A novel COX-1 splice variant termed COX-3, sensitive to
      acetaminophen, was recently discovered by Simmons et al., and is considered to
      play a key role in the biosynthesis of prostanoids known to be important
      mediators in pain and fever. Drugs that preferential block COX-1 also appear to
      act at COX-3. However the existence of COX-3 at the nucleotide sequence level in
      humans has been called to question. A functional COX-3 in humans is still to come
      underlining that the concept of COX-3 is still attractive. Here, we discuss some
      of the implications drawn from the identification of additional functional
      cyclooxygenase members in the generation of bioactive autacoids.

PMID- 14580369
TI  - Prostacyclin and thromboxane A2 production in nitric oxide-deficient hypertension
      in vivo. Effects of high calcium diet and angiotensin receptor blockade.
AB  - The effects of chronic nitric oxide deficiency on prostacyclin and thromboxane
      A(2) production in vivo are unknown. Therefore, we treated rats with N(G)-nitro-L
      arginine methyl ester (L-NAME), and used losartan and high calcium diet as
      antihypertensive treatments. Forty eight Wistar rats were divided into six
      groups: control; losartan (20mgkg(-1)day(-1)); high calcium diet (dietary calcium
      elevated from 1.1% to 3%); L-NAME (20mgkg(-1)day(-1)); losartan+L-NAME and high
      calcium diet+L-NAME. Prostacyclin and thromboxane A(2) production were measured
      after eight weeks as urinary 2,3-dinor-6-keto-PGF(1alpha) and 11-dehydro-TXB(2),
      respectively. Both the high calcium diet and losartan reduced blood pressure in L
      NAME hypertension. Chronic nitric oxide deficiency did not modulate prostacyclin
      production but it nearly doubled thromboxane A(2) production in vivo. This effect
      was not influenced by lowering of blood pressure by blockade of angiotensin II
      type 1 receptors. Independent of the level of blood pressure and blockade of
      nitric oxide synthesis the high calcium diet decreased prostacyclin production by
      one third and increased thromboxane A(2) production almost two-fold in vivo.

PMID- 14580370
TI  - Effect of simvastatin on the uptake and metabolic conversion of palmitic, dihomo
      gamma-linoleic and alpha-linolenic acids in A549 cells.
AB  - It is well known that simvastatin affects cholesterol synthesis. Furthermore it
      inhibits growth and proliferation and perturbs fatty acid metabolism in some cell
      lines. We have studied the effects of simvastatin on the uptake and metabolism of
      exogenous fatty acid in the human lung adenocarcinoma A549 cells. Simvastatin
      inhibited the proliferation of A549, and caused an increment in
      phospholipid/cholesterol ratio due to an increment in phospholipid content
      without affecting cholesterol content. All the fatty acids were uptaken and
      metabolized in both control and treated cells. The conversion of palmitic,
      linoleic and dihomo-gamma-linoleic acids to their metabolites and
      products/precursor ratios for the desaturation and elongation reactions showed
      that simvastatin enhanced the Delta5 desaturation step and altered some
      elongating steps. The machinery for unsaturated fatty acid synthesis in A549 is
      quite sensitive to simvastatin and its effects could have important implication
      taking into account that highly unsaturated fatty acids are involved in the
      regulation of diverse cellular functions by themselves or through their
      metabolites.

PMID- 14580371
TI  - Relationship between endothelin 1 and nitric oxide system in the corpus luteum
      regression.
AB  - The present study was designed to investigate the relationship between the nitric
      oxide (NO) system and endothelin 1 (ET-1) in the mechanism of corpus luteum (CL)
      development and consequently regression in rats. We first evaluated basal ET-1
      levels in ovarian tissue from rats with different stages of CL development. An
      increased ovarian ET-1 content was found during CL regression. In a dose
      department response, ET-1 decreased progesterone (P4) and increased prostaglandin
      (PG) PGF2alpha production. By means of a competitive nitric oxide synthase (NOS)
      inhibitor: L-nitro arginine methyl ester (L-NAME) and a slow NO releasing:
      diethyl-aminetriamine (DETA-NONOate), we demonstrated that NO system could be the
      intermediary in the ET-1 diminishing P4 production. The Western blot analysis
      revealed an increase on iNOS while eNOS protein expression was diminished. We
      also found a diminution of total NOS activity after ET-1 treatment. These data
      suggest the existence of a functional relationship between ET-1 and NOS isoforms
      leading the regulation of CL functionally.

PMID- 14580372
TI  - Intra-uterine transmission of disease.
AB  - Fetal development is dependent on maternal supply of fuels and building blocks.
      Disturbed maternal metabolism or inappropriate maternal nutrition confronts the
      fetus with an unfavourable intra-uterine milieu. Structural and functional
      adaptations occur during development and maturation of organs. Consequences of
      these fetal alterations persist postnatally and may result in metabolic
      alterations throughout life. Gestational diabetes can occur in these offspring
      and transmit the effect to the next generation. These alterations in fetal
      development can be associated with fetal macrosomia (maternal diabetes) or fetal
      growth-restriction (maternal/fetal malnutrition). The relation between birth
      weight and later metabolic disease therefore is U-shaped. Adult metabolic
      condition is thus to a considerable extent programmed in utero, fetal and
      neonatal weight being symptoms of disturbed fetal development. This concept of
      intra-uterine programming of disease is illustrated with a review of
      epidemiological human studies and experimental animal studies.

PMID- 14580373
TI  - Alpha-2 macroglobulin controls trophoblast positioning in mouse implantation
      sites.
AB  - In humans, functional deficiency of alpha-2M is not known, implying alpha 2M is
      essential for gestational success. Mice, deficient in two members of the alpha-2
      Macroglobulin (alpha 2M) family, i.e. alpha-2 macroglobulin (MAM) and
      murinoglobulin-1 (MUG-1) are viable, fertile and phenotypically normal, unless
      stressed (Am J Pathol, 155 (1999), 983). Here, we analysed implantation sites in
      MAM(-/-)/MUG-1(-/-)mice during pregnancy, a strong physiological stressor.
      Despite some post-implantation fetal loss, mean litter size was comparable to
      congenic C57Bl/6J (B6) mice, but MAM(-/-)/MUG-1(-/-)pups were significantly
      lighter and the sex ratio was skewed towards males. Implantation sites appeared
      histologically normal up to gestational day (gd) 8. By gd 10, extensive over
      development of trophoblasts was evident, accompanied by relative deficits in
      decidua, in the mural mesometrial lymphoid aggregates of pregnancy and in uterine
      Natural Killer cells. At gd 10-12, decidual spiral arteries were dilated but
      abnormally cuffed by trophoblasts that extended anomalously, for midgestation, to
      the myometrial circular smooth muscle. Ultrastructurally, trophoblasts in the
      mesometrial decidua made intimate contact with endothelial cells that were
      shedding membrane fragments. These findings demonstrate that alpha 2M, and
      thereby proteinases and/or cytokines whose bio-availability is regulated by alpha
      2M, exert significant decidual regulation on trophoblast invasion.

PMID- 14580374
TI  - IL-1 beta is a better inducer of apoptosis in human fetal membranes than IL-6.
AB  - The objective of this study was to compare two of the inflammatory cytokines (IL
      1 and IL-6) elevated in both preterm labour and preterm premature rupture of the
      membranes (pPROM), with respect to their ability to induce fetal membrane
      apoptosis. Fetal membranes collected from women at term were placed in an organ
      explant system and stimulated with recombinant human IL-1 beta and IL-6. The
      expression patterns of pro-apoptotic genes (Fas, FasL, TRADD, FADD) and caspases
      2, 3, 8, 9 were studied using PCR. Caspase activity and DNA fragmentation were
      studied using substrate assays and TUNEL respectively. Caspase 8 and 9
      expressions were induced in IL-1 beta and IL-6 treated amniochorion. Caspase 2
      expression was seen only in IL-1 beta stimulated tissues. When compared to
      control, IL-1 beta increased caspase 2, 3, 8 and 9 activities, whereas IL-6
      treated membranes did not exhibit a significant change. DNA fragmentation was
      seen in greater numbers after IL-1 beta treatment than after IL-6 treatment. This
      study demonstrates that IL-1 beta is a better inducer of apoptosis in normal
      human fetal membranes than IL-6.

PMID- 14580375
TI  - Apoptosis of extravillous trophoblast cells limits the trophoblast invasion in
      uterine but not in tubal pregnancy during first trimester.
AB  - During the first trimester of pregnancy extravillous trophoblast cells (EVT)
      invade the maternal decidua. Invasion normally is reduced from the second
      trimester onwards and stops in the inner third of the myometrium. By contrast, in
      extrauterine tubal pregnancy, trophoblast invasion may even penetrate the tubal
      wall, which ultimately leads to the rupture of the fallopian tube. Induction of
      apoptosis of EVT cells, by maternal immune competent cells, may be an important
      mechanism to limit EVT invasion in uterine pregnancy. Tissue specimens from first
      and second trimester uterine pregnancy and first trimester tubal pregnancy were
      analyzed for apoptosis by TUNEL- and M30-staining. By immunohistochemical double
      labelling, maternal leukocyte subtypes were co-localized to apoptotic cells and
      in this context, the number of CD56(+)NK cells was analyzed. Our data show that
      apoptosis is confined to the decidua basalis. Most apoptotic cells are single
      cytokeratin-positive epithelial cells residing in the stromal compartment.
      Consequently these cells can only be EVT cells. Maternal leukocytes are not
      apoptotic. They are located in close contact to apoptotic cells. The number of
      apoptotic cells in the second trimester (1.8+/-0.7 per cent) is reduced compared
      to first trimester (5.6+/-0.7 per cent) of uterine pregnancy. In parallel, the
      number of NK cells declines from first (24.4+/-2.9) to second (12.4+/-1.8)
      trimester. Furthermore, apoptosis is significantly reduced in ectopic (0.9+/-0.3
      per cent) compared to eutopic first trimester pregnancies. Consequently, we
      suggest that in first trimester uterine pregnancy, induction of EVT cell
      apoptosis by the maternal immune system is one mechanism to limit EVT invasion.
      During the second trimester, in parallel to declining numbers of NK cells, the
      mechanism changes. However, in tubal pregnancy due to differing immunological
      microenvironments at the ectopic implantation site, apoptosis induction fails,
      which deleteriously may result in uncontrolled invasion and penetration of the
      tubal wall.

PMID- 14580376
TI  - Oxygen-regulated expression of TGF-beta 3, a growth factor involved in
      trophoblast differentiation.
AB  - The transforming growth factor-beta 3 (TGF-beta 3) is involved in oxygen
      dependent differentiation processes during placental development and pregnancy
      disorders. However, the importance of oxygen partial pressure for the regulation
      of TGF-beta 3 expression is presently unclear. We and others presented
      preliminary evidence that the hypoxia-inducible factor-1 (HIF-1) confers TGF-beta
      3 transcription but it was unknown whether this occurred directly or indirectly.
      To analyze how HIF-1 regulates TGF-beta 3 gene transcription, we cloned and
      sequenced the mouse TGF-beta 3 promoter region. Multiple putative HIF-1 binding
      sites (HBSs) were identified, many of which co-localized with two G+C rich CpG
      islands 5' to the TGF-beta 3 transcription start site. A 6.8 kb fragment of the
      TGF-beta 3 promoter induced reporter gene expression under hypoxic conditions or
      when treated with an iron chelator known to stabilize and activate the HIF-1
      alpha subunit. Deletion of a 2.4 kb fragment upstream of the distal CpG island
      abolished inducibility of reporter gene expression. Two HBSs (HBS1 and HBS6) that
      bound the HIF-1 protein could be identified within this 2.4 kb fragment. These
      results suggest that TGF-beta 3 gene expression is directly regulated by HIF-1.

PMID- 14580377
TI  - Basal membrane localization of MRP1 in human placental trophoblast.
AB  - The placental trophoblast is considered to act as a barrier between mother and
      fetus, mediating the exchange of various materials across the placenta. ATP
      binding cassette (ABC) transporters such as P-glycoprotein (P-gp) and multidrug
      resistance protein (MRP) are expressed in the placenta and function as efflux
      transport systems for xenobiotics. In the present study, we aimed to determine
      the localization of MRP1 in the human placenta in comparison with that of P-gp.
      Western blotting analysis with human placental membrane vesicles indicated that P
      gp and MRP1 are localized on the brush-border membranes and basal membranes,
      respectively. Immunohistochemical analysis with human normal full-term placenta
      showed that anti-P-gp monoclonal antibody F4 stained the brush-border side of the
      trophoblast cells, whereas anti-MRP1 monoclonal antibody MRPr1 stained the basal
      side. These results confirm that P-gp and MRP1 are located on the brush-border
      membranes and basal membranes, respectively, of human full-term placental
      trophoblast. MRP1 was also detected on the abluminal side of blood vessels in the
      villi. Accordingly, MRP1 may play a role distinct from that of P-gp, which is
      considered to restrict the influx of xenobiotics into the fetus.

PMID- 14580378
TI  - A two-colour fluorescence assay for the measurement of syncytial fusion between
      trophoblast-derived cell lines.
AB  - Syncytial fusion is a key event in implantation and placentation. Its regulation
      is only poorly understood. We present a cell-cell fusion assay based on staining
      of cells in two portions with a green and a red fluorescent cytoplasmic dye that
      become intracellularly mixed only after syncytial fusion. We quantified cell-cell
      fusion by fluorescence microscopy in choriocarcinoma cell lines BeWo, JAR and
      JEG3 and in some non-trophoblastic cell lines and found clear differences in
      fusion behaviour. Only BeWo cells fused with each other, while the other cell
      lines tested did not. BeWo cells also fused with all other cell lines tested. The
      efficiency of cell-cell fusion of BeWo cells was stimulated by forskolin. We
      tried to correlate messenger levels of syncytin and its receptor RDR with the
      fusion index of choriocarcinoma cells. BeWo and JAR cells contained readily
      detectable and forskolin-inducible levels of syncytin mRNA, whereas this
      messenger was barely detectable in JEG3 cells. RDR transcript levels were similar
      in all cell lines tested and were unaffected by forskolin treatment. The data
      suggests that the expression of syncytin and RDR messengers alone does not
      guarantee successful fusion. The fusion assay presented in this paper is a useful
      tool to study syncytial fusion in an accurate and quantitative way.

PMID- 14580379
TI  - Augmented PLA2 activity in pre-eclamptic decidual tissue--a key player in the
      pathophysiology of 'acute atherosis' in pre-eclampsia?
AB  - Decidual acute atherosis is associated with pre-eclampsia, but the underlying
      mechanism is still unclear. We have previously demonstrated elevated level of the
      oxidative stress marker 8-isoprostaglandin F(2 alpha)(8-isoprostane) and lipids
      in pre-eclamptic decidual tissue. Arachidonic acid (AA) in tissue phospholipids
      is a source for 8-isoprostane generation, and 8-isoprostane is liberated from
      tissue phospholipids by phospholipase A(2)(PLA(2)). The aims of this study were
      to explore whether AA content or PLA(2)expression in pre-eclamptic decidual
      tissue differed from controls. Decidua basalis tissues were obtained by vacuum
      aspiration at Caesarean delivery in pre-eclamptic and control pregnancies. We
      demonstrated a statistically significantly higher total PLA(2)activity in pre
      eclamptic decidua compared to control tissue. On the other hand, no differences
      in AA content of tissue phospholipids or protein expression of secretory and
      cytosolic PLA(2)between pre-eclamptic and control decidual tissue were found. In
      conclusion, the elevated level of free 8-isoprostane in pre-eclamptic decidual
      tissue could be caused by augmented PLA(2)activity. We speculate that an elevated
      PLA(2)enzyme activity in pre-eclamptic decidual tissue could be of importance in
      the pathogenesis of 'acute atherosis', comparable to the atherogenesis in
      cardiovascular diseases.

PMID- 14580380
TI  - Nitric oxide-mediated vascular tone in the fetal placental circulation of
      patients with type 1 diabetes mellitus.
AB  - Endothelium-derived nitric oxide (NO) plays a key role in the regulation of
      vascular tone in health and disease. The present study addresses the contribution
      of NO to the baseline vascular tone in the fetal placental circulation of type 1
      diabetic women. To this end, we performed ex-vivo dual perfusions of isolated
      cotyledons from seven women with type 1 diabetes mellitus and 24 healthy women.
      The fetal arterial pressure was considered to be a measure of fetal vascular
      resistance. The contribution of NO to the baseline vascular tone of the fetal
      placental circulation was quantified by addition of the NO-synthase inhibitor
      N(G)-nitro-arginine-methylester (L-NAME). Apart from the diabetic state, we
      studied the influence of exogenous insulin on the response to L-NAME. Mean (+/
      SEM) baseline fetal arterial pressure was higher in diabetes (25.7+/-3.4 mm Hg vs
      18.0+/-1.7 mm Hg, P<0.05). Maximum perfusion pressure after L-NAME was 87.9+/-7.1
      mm Hg in diabetes vs 58.9+/-4.5 mm Hg in controls (P<0.01). The net L-NAME
      induced increase in fetal arterial pressure was higher in diabetes (62.2+/-9.1 mm
      Hg vs 40.9+/-3.5 mm Hg, P<0.05). Although insulin induced a shift to the left of
      the L-NAME-curve, the net L-NAME-induced increase in fetal arterial pressure was
      not affected. We conclude that diabetes is associated with an increased baseline
      vascular tone of the fetal placental vascular bed. This can not be explained by
      attenuated NO-mediated effects. In contrast, the activity of the NO-pathway seems
      to be increased in diabetes. The latter observation seems not to be caused by
      high insulin levels.

PMID- 14580381
TI  - Increased oxidative stress in pre-eclamptic placenta is associated with altered
      proteasome activity and protein patterns.
AB  - Analysis of the amount of oxidatively damaged proteins in placenta proteins from
      normal pregnancies and pre-eclampsia revealed a relative increase of about 30 per
      cent of damaged proteins in pre-eclamptic placenta. Previous work has
      demonstrated that these cell- and tissue-damaging oxidatively stressed proteins
      are metabolized particularly by the 20S proteasome. Evaluation of the proteasomal
      activity revealed a significantly reduced proteasome function in pre-eclamptic
      placenta by about 30 per cent, suggesting that the accumulation of oxidatively
      damaged proteins in pre-eclampsia is associated with reduced proteasomal
      activity. To investigate these effects at molecular levels, separation of
      placental proteins by two-dimensional SDS-PAGE and subsequent anti-proteasome
      Western blot revealed several sets of approximately 20 kDa and 30 kDa protein
      subunits in normal placenta which appear at low or undetectable expression levels
      in pre-eclamptic placenta. Control Western blots against the placenta protein 14
      (PP14) demonstrated equal loading and no significant differences in the PP14
      protein patterns. These data suggested that alteration of the multifactorial
      proteasomal protein complex in pre-eclamptic placenta is accompanied by reduced
      metabolization of oxidatively damaged proteins. Consequently, the accumulation of
      these damaged proteins in the placenta may be associated with metabolic
      interference and thus contribute to certain developments of pre-eclampsia. Silver
      staining of the two-dimensional SDS-PAGE revealed a variety of acidic proteins in
      the range of 20 kDa and 45 kDa, respectively, which are differentially expressed
      in normal and pre-eclamptic placenta and thus provide further analytic potential
      for metabolic interference.

PMID- 14580382
TI  - Nutritional intake and placental size in gestational diabetic pregnancies--a
      preliminary observation.
AB  - A disproportionately large placenta may represent an adaptive response to adverse
      intrauterine conditions. Both maternal nutritional intake and presence of
      gestational diabetes (GDM) have been found to affect relative placental growth.
      As dietary modification is part of the standard management in GDM women, the
      observed increase in placental size in these women may be partly due to dietary
      modification. In this study, we set out to examine the relationship between
      dietary intake and placental size in GDM pregnancies. Food diaries for five
      consecutive days for 52 women diagnosed with GDM were obtained to assess their
      nutritional intake in terms of total calories, carbohydrate, protein and fat.
      Spearman's correlations were calculated for nutritional intake and various
      factors that may correlate with placental weight. There was a significant inverse
      relationship (P=0.021) between placental weight and protein intake. No
      correlations with the other two nutritional components could be demonstrated.
      Maternal nutritional intake was not correlated with infant birthweight. It is
      possible that dietary modulations improve GDM pregnancy outcome, not only by
      improving glycaemic controls but also by affecting placental growth by altering
      the proportion of protein intake.

PMID- 14580383
TI  - Identification of the CB1 cannabinoid receptor and fatty acid amide hydrolase
      (FAAH) in the human placenta.
AB  - Synthetic cannabinoids, the psychoactive components of the Cannabis sativa
      (marijuana) plant and their endogenous counterparts, act through two G protein
      coupled receptors, CB1 and CB2. The endocannabinoids are metabolized by fatty
      acid amide hydrolase (FAAH). Previous research has described the impact of
      cannabis consumption on pregnancy, potential roles of endocannabinoids and
      abnormalities of FAAH expression in recurrent miscarriage and pregnancy. However,
      the cellular localization of the CB1 cannabinoid receptor and FAAH in the human
      placenta has not been determined. We have examined CB1 receptor and FAAH
      expression in human term placenta by immunohistochemistry. CB1 receptor was found
      to be present in all layers of the membrane, with particularly strong expression
      in the amniotic epithelium and reticular cells and cells of the maternal decidua
      layer. Moderate expression was observed in the chorionic cytotrophoblasts. The
      expression of FAAH was highest in the amniotic epithelial cells, chorionic
      cytotrophoblast and maternal decidua layer. Our results suggest that the human
      placenta is a likely target for cannabinoid action and metabolism. This is
      consistent with a placental site of action of endocannabinoids and cannabis being
      responsible, at least in part, for the poor outcomes associated with cannabis
      consumption and pathology in the endocannabinoid system during pregnancy.

PMID- 14580387
TI  - Acanthamoeba interactions with human brain microvascular endothelial cells.
AB  - Acanthamoeba are opportunistic protozoan parasites that can cause fatal
      granulomatous amoebic encephalitis, however, the pathogenic mechanisms associated
      with this disease remain unclear. One of the primary factors in Acanthamoeba
      encephalitis is the haematogenous spread, followed by invasion of the blood-brain
      barrier resulting in the transmigration of Acanthamoeba into the central nervous
      system. In this study, we have used human brain microvascular endothelial cells,
      which constitute the blood-brain barrier and studied their interactions with
      Acanthamoeba. Using in vitro cultures, we showed that Acanthamoeba isolates
      belonging to genotypes T3, T4 and T11, exhibited increased cytotoxicity on human
      brain microvascular endothelial cells as well as exhibited higher binding and
      were considered potential pathogens. In contrast, Acanthamoeba isolates belonging
      to genotypes T2 and T7 exhibited minimal cytotoxicity and significantly less
      binding to human brain microvascular endothelial cells (P< 0.01). Furthermore,
      exogenous alpha-mannose inhibited binding but increased cytotoxicity of human
      brain microvascular endothelial cells. This is the first demonstration of
      Acanthamoeba interactions with primary human brain microvascular endothelial
      cells.

PMID- 14580388
TI  - Genetic analysis of the formation of the Ysc-Yop translocation pore in
      macrophages by Yersinia enterocolitica: role of LcrV, YscF and YopN.
AB  - The Ysc-Yop type III secretion (TTS) system allows extracellular Yersinia
      bacteria, adhering to eukaryotic target cells, to inject Yop effector proteins in
      the cytosol of these cells. The secretion apparatus, called the injectisome, ends
      up with a needle-like structure made of YscF. YopN, one of the proteins secreted
      by the injectisome is thought to act as a plug. YopB, YopD and LcrV, three other
      proteins secreted by the injectisome and called 'translocators' form a pore
      allowing translocation of the Yop effectors across the target cell plasma
      membrane. Here, we tested the role of LcrV, YscF and YopN in the formation of
      this pore in macrophages by monitoring the release of the low-molecular-weight
      fluorescent dye BCECF (2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein,
      acetoxymethyl ester, 623Da) and of the high-molecular-weight lactate
      dehydrogenase (LDH, 135 kDa). BCECF is released through the translocation pore
      itself provided no Yop effector is trafficking through the channel. In contrast,
      LDH is released by the osmotic lysis of the target cell that occurs after pore
      formation. This release is reduced by the GAP activity of YopE. In order to study
      the role of LcrV, one has to circumvent the regulatory effect of LcrV on the
      synthesis of YopB and YopD. We observed here that this regulatory role of LcrV is
      lost in a yopQ mutant and hence we studied the role of LcrV in a yopQ mutant
      background. A lcrV, yopQ double mutant was deficient in pore formation while able
      to produce YopB and YopD. Pore formation was restored by the introduction of
      lcrV(+) but not yopQ(+) confirming that LcrV itself is directly required for pore
      formation. Bacteria secreting only YopB, YopD and LcrV could form pores, showing
      that YopB, YopD and LcrV are sufficient for pore formation provided they are
      secreted by the same bacterium. LcrV is not involved in secretion of YopB and
      YopD as suggested previously. Bacteria producing normal Ysc injectisomes,
      including the YscF needle but no translocators did not form pores, indicating
      that the needle is not sufficient by itself for pore formation, as was also
      suggested. yopN mutant bacteria formed needles and released BCECF even if they
      secreted the effectors. This observation suggests that many translocation pores
      are not filled in the absence of YopN and thus that YopN might form a link
      between the needle and the pore, guiding the effectors.

PMID- 14580389
TI  - Porphyromonas gingivalis induces murine macrophage foam cell formation.
AB  - Atherosclerosis is a complex pathologic process initialed by the formation of
      cholesterol-rich plaque. Macrophages play a central role in the development of
      atherosclerosis, specifically in the initial accumulation of cholesterol in the
      arterial wall. It has been suggested that infection and chronic inflammatory
      conditions such as periodontitis may influence the atherosclerosis process.
      Porphyromonas gingivalis, one of the major pathogens involved in periodontitis,
      has been detected in human atheromas, suggesting that P. gingivalis infection may
      be associated with atherosclerosis. However, a causal relationship between this
      pathogen and the disease process has not yet been established. The purpose of the
      present investigation was to determine whether P. gingivalis could induce
      macrophages to form foam cells using the murine macrophage cell line (J774) as a
      model system. For inocula smaller than one bacterium per ten cells, P. gingivalis
      381, as well as its lipopolysaccharide (LPS), induced foam cell formation of
      macrophages when cultured in the presence of human low-density lipoprotein (LDL).
      Infection of macrophages with increasing doses of P. gingivalis resulted in
      higher levels of foam cell formation. More than 70% of the cultured macrophages
      form cholesterol ester droplet-rich cells in the presence of 100 mug/ml of LDL
      when the inocula was more than 10 bacteria per cell. Low concentrations of P.
      gingivalis outer membrane vesicles also induced foam cell formation in the
      presence of LDL. In addition, it was demonstrated that P. gingivalis LPS alone
      was able to induce macrophage foam cell formation. P. gingivalis and its vesicles
      not only promoted LDL binding to macrophages but also induced macrophages to
      modify native LDL, which plays an important role in foam cell formation and the
      pathogenesis of atherosclerosis. Therefore, P. gingivalis cells or its vesicles
      released from periodontal lesions into the circulation may deliver virulence
      factor(s) such as LPS to the arterial wall to initiate or promote foam cell
      formation in macrophages and contribute to atheroma development.

PMID- 14580390
TI  - Detection of genetic diversity in linear plasmids 28-3 and 36 in Borrelia
      burgdorferi sensu stricto isolates by subtractive hybridization.
AB  - Recent studies based on sequence divergence in the ospC gene have identified
      limited subpopulations of B. burgdorferi associated with invasive human disease.
      Spirochetes with certain OspC types never cause human disease, while some others
      cause local infection at the primary skin site but do not hematogenously
      disseminate. Only four OspC genotypes (A, B, I and K) are responsible for
      disseminated disease and are found in the blood and cerebrospinal fluid, and
      hence are termed invasive strains. Subtractive hybridization was carried out
      between a prototype of a low passage invasive type, strain B31, and a strain
      associated only with local infection, group E, to identify genes associated with
      hematogenous dissemination. Two clones isolated from the subtraction library were
      unique to the B31 genome and mapped to locus BBH26 located on linear plasmid 28-3
      (lp28-3) and to locus BBK48 located on linear plasmid 36 (lp36). Sequence
      analysis of the BBH26 locus revealed an amino acid repeat motif in the group E
      DNA that was absent in the B31 genome. This in-frame repeat motif was present yet
      variable in DNA isolated from several major OspC groups. However, no consistent
      sequence diversity was noted when other invasive and non-invasive strains were
      compared. In contrast, analysis of the BBK48 locus revealed a striking
      distinction between invasive and non-invasive spirochetes. PCR and Southern blot
      analysis indicated this locus was only present in invasive groups A, B, I, and K.
      BBK48 is a member of a gene family clustered on lp36. Therefore, these findings
      indicate that this genetic loci may participate in differentiating pathogens from
      non-pathogens and that its presence, which is correlated with ospC type, may play
      a role determining infectivity in humans.

PMID- 14580391
TI  - Salmonella enterica serovar Dublin strains which are Vi antigen-positive use type
      IVB pili for bacterial self-association and human intestinal cell entry.
AB  - Some strains of Salmonella enterica serovar Dublin are Vi antigen-positive. S.
      enterica serovar Typhi uses Type IVB pili, encoded adjacent to the viaB locus
      required for Vi antigen synthesis, to facilitate both eukaryotic cell attachment
      and bacterial self-association under conditions that favour DNA supercoiling.
      These pilus-mediated events may be important in typhoid fever pathogenesis. A
      survey of 17 isolates of S. enterica serovar Dublin showed that all strains which
      carried the viaB region also carried a serovar Typhi-like Type IVB pil operon,
      and all serovar Dublin Vi antigen-negative isolates lacked the pil operon. The
      pil operon was completely sequenced from one of the Vi(+) serovar Dublin strains,
      and was almost identical (4 nt changes; 3 aa changes, in over 10 kb) to that of
      serovar Typhi. A pilS mutant of one serovar Dublin strain was constructed, and
      shown to invade cultured human intestinal INT407 cells to an extent only 20% that
      of the wild-type parent. Purified prePilS protein inhibited INT407 cell entry by
      serovar Dublin. The wild-type serovar Dublin strain, but not the pilS mutant,
      self-associated. The data suggest that the serovar Dublin Type IVB pil operon may
      increase the human-invasiveness of serovar Dublin, compared to pil-free strains.

PMID- 14580392
TI  - Caspase activation during Haemophilus somnus lipooligosaccharide-mediated
      apoptosis of bovine endothelial cells.
AB  - Vasculitis is commonly seen during systemic Haemophilus somnus infections.
      Although, the mechanism of vascular damage is not completely understood, in a
      previous report we demonstrated that H. somnus and its lipooligosaccharide (LOS)
      induced apoptosis in bovine pulmonary artery endothelial cells in vitro. In the
      present study, we investigated the role of caspase activation in LOS-mediated
      apoptosis of bovine endothelial cells. Exposure to H. somnus LOS induced caspase
      3 activation and chromatin condensation in endothelial cells. These responses
      were blocked by the addition of a pan-caspase inhibitor (z-VAD-fmk) or capase-3
      inhibitor (DEVD-fmk). Incubation of endothelial cells with H. somnus LOS also
      induced activation of the initiator caspases, caspases-8 and 9, with the activity
      of the former increasing more rapidly than the latter. Addition of a caspase-8
      inhibitor (IETD-fmk) significantly reduced LOS-mediated apoptosis, whereas,
      addition of a caspase-9 inhibitor (LEHD-fmk) had little effect. These data
      suggest that LOS-mediated activation of caspase-3 and apoptosis of endothelial
      cells is caspase-8 dependent.

PMID- 14580393
TI  - Plasminogen-mediated group A streptococcal adherence to and pericellular invasion
      of human pharyngeal cells.
AB  - Alpha-enolase (SEN) is a strong plasminogen-binding protein on the surface of
      group A streptococci (GAS). By flow cytometry and immunofluorescence analyses and
      using human enolase-specific antibody, human pharyngeal cells (Detroit 562) also
      were found to express enolase on their surface. Detroit 562 cells preferentially
      bound to Lys-plasminogen and this binding was inhibited in the presence of a
      lysine analog, epsilon-aminocaproic acid and by carboxypeptidase-B treatment
      suggesting that the C-terminal lysine residue of the putative pharyngeal cell
      receptor(s) may play an important role in plasminogen-binding. The increased
      plasminogen-binding in the presence of free enolase indicated the presence of an
      enolase/SEN-specific receptor on the pharyngeal cell surface. GAS, when precoated
      with Lys-plasminogen, adhered to pharyngeal cells significantly more in numbers
      than when precoated with fibronectin or laminin. Similarly, GAS adhered also
      significantly more in numbers to pharyngeal cells which were precoated with Lys
      plasminogen. GAS adhered similarly in high numbers when incubated with pharyngeal
      cells in the presence of soluble plasminogen. The de novo pharyngeal cell-bound
      protease activity, created as a result of activation of bound plasminogen by t
      PA, indicated its potential role in pericellular fibrinolytic activity. Further
      GAS with tPA-activated plasminogen bound on their surface penetrated through
      Transwell-grown pharyngeal cells in significantly higher numbers. Together, the
      results presented in this study highlight a novel function of plasminogen in
      streptococcal adherence to pharyngeal cells and a newly discovered streptococcal
      ability to pericellularly invade pharyngeal cells as a result of tPA/endogenous
      plasminogen activator-mediated proteolytic activity.

PMID- 14580394
TI  - Sequence variation at a Bmy I/Rsa I restriction site in ovine herpes virus 2.
AB  - DNA samples extracted from a bovine brain, one blood and one buffy coat sample
      from three cattle with malignant catarrhal fever, and from 47 samples of pooled
      sheep sera, were amplified by nested polymerase chain reaction (PCR) using
      primers specific for ovine herpes virus 2 (OHV-2). Confirmation of the
      specificity of the amplified DNA segment by restriction enzyme analysis with Rsa
      I and Bmy I as described by Baxter et al. was obtained in most samples. Nine
      amplified DNA samples could not be digested, or were only partially cut, with
      these enzymes. Sequencing of six samples revealed a two-nucleotide substitution
      in the middle of the restriction site (AA vs. CG) in four of these samples (the
      bovine brain and three sera), and two peaks at each of these positions (C or A, G
      or A) in two samples from pooled ovine serum. These results indicate the
      existence of a variant of OHV-2, and that both the previously sequenced OHV-2 and
      the variant were present in some samples of pooled ovine serum.

PMID- 14580395
TI  - Comparison of culture, polymerase chain reaction (PCR), TaqMan Salmonella, and
      Transia Card Salmonella assays for detection of Salmonella spp. in naturally
      contaminated ground chicken, ground turkey, and ground beef.
AB  - Four types of assays were evaluated for the detection of Salmonella spp. in
      retail ground chicken (86 packages), ground turkey (104 packages), and ground
      beef (54 packages). Two 25 g samples from each package were separately subjected
      to pre-enrichment in buffered peptone water for 20 h at 37 degrees C followed by
      enrichment in Rappaport Vassiliadis (RV) broth for 20 h at 42 degrees C. The RV
      enrichments were plated onto Rambach agar, Rainbow Agar Salmonella, and XLT4
      agar, and were also tested by a PCR assay targeting the Salmonella invA gene, as
      well as by the TaqMan Salmonella PCR assay. Additionally, the RV enrichments were
      tested using the Transia Card Salmonella immunoassay. Results showed that 16.8,
      24.0, 28.8, and 26.4% of turkey samples were positive for Salmonella spp. by
      culture, PCR, TaqMan PCR, and Transia Card Salmonella assays, respectively.
      Eighteen, 28.5, 35.5, and 34.9% of chicken samples were positive by culture, PCR,
      TaqMan PCR, and Transia Card Salmonella assays, respectively, and 6.5, 6.5, 6.5,
      and 18.5% of ground beef samples were positive by the four assays, respectively.
      Analysis of the data using the kappa statistic showed that there was substantial
      to excellent agreement between the PCR and TaqMan PCR assays and between the PCR
      and culture assays (kappa coefficients ranging from 0.67 to 0.87), while there
      was poor to fair agreement between the results of the Transia Card Salmonella
      assay and the other methods (kappa coefficients ranging from 0.28 to 0.32).
      Overall, results showed that the PCR-based assays were more sensitive than the
      culture method, and the culture and PCR-based assays were more specific than the
      immunoassay for detection of Salmonella in ground chicken, turkey, and beef due
      to the occurrence of false positive results using the immunoassay.

PMID- 14580396
TI  - Real-time PCR for the detection of Giardia lamblia.
AB  - Microscopy is considered to be the gold standard for diagnosis of Giardia lamblia
      infection. However, this method is time-consuming and not very sensitive. We
      developed a real-time PCR assay based on the small subunit ribosomal RNA gene of
      G. lamblia for the specific detection of G. lamblia DNA in stool samples and
      thereafter compared the results with microscopy and antigen detection. The G.
      lamblia real-time PCR was positive in 102 of 104 fecal samples known to contain
      G. lamblia cysts and was positive in 10 fecal samples in which G. lamblia antigen
      was detected but in which no cysts were found with microscopic examination of
      concentrated fecal samples. The real-time PCR is as specific and sensitive as
      antigen detection and is more sensitive than microscopy. Moreover, in two
      patients we were able to detect G. lamblia earlier in the course of infection
      than with any of the other methods.

PMID- 14580397
TI  - A strategy based on 5' nuclease multiplex PCR to detect enterotoxin genes sea to
      sej of Staphylococcus aureus.
AB  - We describe the development of a strategy based on 5' nuclease multiplex PCR for
      the rapid detection of nine enterotoxin genes (sea, seb, sec, sed, see, seg, seh,
      sei, sej) of Staphylococcus aureus. The genotyping scheme consists in identifying
      these nine enterotoxin genes by three 5' nuclease Triplex-PCR assays. The
      strategy was evaluated using a collection of S. aureus reference strains
      previously examined with conventional PCR assays, and by testing previously
      characterized food S. aureus field strains. The 5' nuclease Triplex-PCR assays
      correctly detected the se genes in all the reference strains. In tests with field
      strains there was generally excellent agreement with the results obtained by
      conventional PCR, except for some strains harbouring variant se genes. The
      detection limits of the Triplex-PCR assays evaluated using fivefold dilution of
      recombinant plasmids for each se gene ranged from 16 to 2000 copies of target se
      genes in the PCR tube. The 5' nuclease Triplex-PCR assays developed are fast and
      specific, and provide a useful diagnostic tool for the detection and genotyping
      of se genes. The development of this method is an improvement that should
      facilitate epidemiological investigations of staphylococcal food poisoning
      outbreaks.

PMID- 14580398
TI  - Direct estimation of biofilm density on different pipe material coupons using a
      specific DNA-probe.
AB  - A variety of approaches to quantify biomass in biofilms without disruption due to
      detachment have been developed over the years. One basic approach is the
      combination of advanced microscopy with molecular staining. However, many stains
      (e.g. 4',6-diamino-2-phenylindole, acridine orange or live-dead stains) can be
      non-specific when corrosion products, precipitates, and pipe material are
      present. In addition, some pipe materials cause high background when using
      epifluorescent microscopy. The new refinement discussed in this presentation used
      fluorescence spectroscopy to obtain the spectra from four common distribution
      system pipe materials: PVC, 'concrete' lined cast iron, cast iron, and galvanized
      steel. The emission maximum for all four materials was between 500 and 550 nm,
      but emissions radically decreased around 575-600 nm. A molecular probe, BO-PRO-3
      (Molecular Probes, Inc., Eugene, OR, USA) was identified which has an emission
      intensity maximum at 599 nm (red), with emission intensity 200 times greater when
      it is bound to DNA. The BO-PRO-3 has greatly reduced non-specific staining and
      background problems. In the preliminary experiment, using diluted waste water, a
      significant exponential relationship was found between stained surface area/total
      area ratio and fixed biofilm inventory measurements from scraping heterotrophic
      plate counts (SHPC) on R2A medium. In addition, the biofilm inventory on
      different pipe material coupons from pilot distribution systems was also
      correlated to the stained surface area fraction and SHPC.

PMID- 14580399
TI  - The use of suppression subtractive hybridization for the study of SDF-1alpha
      induced gene-expression in human endothelial cells.
AB  - Stromal cell-derived factor-1 (SDF-1), the only ligand of the CXCR4 receptor, is
      mainly known as a chemotactic factor for hematopoietic progenitor cells. However,
      studies of knock-out mice have shown malformation of different organ-systems
      suggesting that SDF-1 may have a role in angiogenesis and cardiac and cerebral
      development. However, the underlying mechanisms of its action are largely
      unknown. Therefore, we performed suppression subtractive hybridization (SSH) in
      order to identify genes that are differentially expressed after stimulation of
      human arterial endothelial cells (HUAEC) with SDF-1. Using SSH we found ten
      genes, with varied functions, whose mRNA expression is induced by SDF-1alpha in
      HUAEC. We show that SSH is a reliable method for identifying differentially
      expressed genes and that SDF-1alpha may have more functions than previously
      reported.

PMID- 14580400
TI  - Design considerations and effects of LNA in PCR primers.
AB  - The effects of comprehensive LNA substitution in PCR primers for amplification of
      human genomic DNA targets are presented in this report. Previous research with
      LNA in other applications has shown interesting properties for molecular
      hybridization including enhanced specificity in allele-specific PCR. Here we
      systematically modified PCR primers and conditions for the human genomic DNA
      targets APOB and PAH, along with a beta-globin amplification control, to study
      whether the number and position of LNA residues improves or diminishes
      amplification sensitivity and specificity. It was observed that the design rules
      for LNA substitution in PCR primers are complex and depend upon number, position
      and sequence context. Technical advantages were seen when compared to DNA
      controls for the best LNA primer designs, which were typically one to a few
      centrally located LNA residues. LNA advantages include increased maximum
      annealing temperature (Tmax) and increased signal with limiting primer or Taq DNA
      polymerase. Several well-characterized designs exhibited different efficiencies
      with different brands of hot-start enzymes. Many shorter LNA primers were found
      to be functional compared to same-length non-functional native DNA controls.
      These results show that LNA-substituted PCR primers have potential for use in
      difficult PCR techniques, such as multiplex amplification at higher Tmax, once
      firm LNA primer design rules are established.

PMID- 14580401
TI  - RT-PCR for the pseudogene-free amplification of the glyceraldehyde-3-phosphate
      dehydrogenase gene (gapd).
AB  - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is an enzyme which catalyses the
      conversion of glyceraldehyde-3-phosphate to 1,3 diphosphoglycerate. It is
      considered to be constitutively expressed in all cells, and as such the gene for
      GAPDH (gapd) is commonly used as a benchmark reference in expression studies.
      However, previous investigations have demonstrated that gapd may show altered
      gene expression in a number of disease states and under certain experimental
      conditions, suggesting that results of experiments using gapd as a control should
      be interpreted with caution. Furthermore, consideration must be given to the
      potential co-amplification of pseudogenes of gapd during RT-PCR. Here, we
      describe a method to avoid the amplification of contaminating pseudogenes through
      the design of primers that bind only to genuine gapd mRNA transcript.

PMID- 14580402
TI  - Duplex PCR-RFLP for simultaneous detection of factor V Leiden and prothrombin
      G20210A.
AB  - The authors have used a primer-engineered duplex polymerase chain reaction (PCR) 
      restriction fragment length polymorphism (RFLP) for the simultaneous detection of
      factor V Leiden and prothrombin G20210A mutations. The method involves the
      generation of HindIII RFLPs, and the restricted amplification products are
      analyzed by agarose gel electrophoresis in a single gel lane. This method is
      simple an inexpensive, and readily adaptable to the routine in a clinical
      molecular diagnostic laboratory other that our own.

PMID- 14580553
TI  - Complex biological processes and their central chemical events.

PMID- 14580554
TI  - HIS & HERS, magic magnesium and the ballet of protein synthesis.
AB  - The peptidyl transferase center of the ribosome is literally the mother of all
      protein enzymes, yet it was only recently that the content of its active site was
      found to be RNA and not protein. This review focuses on how this RNA enzyme
      orients its substrates and promotes the chemical reaction that is center stage in
      protein synthesis.

PMID- 14580555
TI  - Feeding the machine: mechanisms of proteasome-catalyzed degradation of
      ubiquitinated proteins.
AB  - The proteasome plays a role in a myriad of intracellular processes from cell
      cycle control to antigen presentation. Central to these processes is the
      targeting of selected proteins for proteasomal degradation via their conjugation
      to ubiquitin. The mechanisms by which the ubiquitin-dependent proteasomal
      proteolysis occurs can be divided into four steps: first, substrate protein
      recognition by its cognate E3 ubiquitin ligase; second, polyubiquitinated protein
      substrate recruitment to the proteasome; third, protein substrate
      deubiquitination; and four, proteolytic chamber pore opening/substrate
      translocation followed by proteolysis. Recent advances include the identification
      of novel E3 ubiquitin ligase recognition determinants, a new isopeptidase
      activity, and a better understanding of how the proteasome's axial channels are
      gated.

PMID- 14580556
TI  - Mechanisms for photosystems I and II.
AB  - Using structural information from recently published crystal structures of
      photosystems I and II, the processes of excitation energy transfer and electron
      transfer in oxygenic photosynthesis have been studied in great detail by
      experimental and theoretical methods. Although both systems share numerous common
      structural and functional features, efficiency and regulation are differently
      weighted in the individual processes that are involved in the transformation of
      light energy into chemical energy in the two complexes.

PMID- 14580557
TI  - Mechanism for electron transfer within and between proteins.
AB  - Examination of a growing range of electron transfer proteins is clarifying what
      design elements are and are not naturally selected. Intraprotein electron
      transfer between natural redox centers is generally engineered to be robust and
      resistant to mutational changes and thermal fluctuations, by using chains of
      redox centers connected by electron tunneling distances of 14 A or less. This
      assures that tunneling rates are faster than the typical millisecond bond
      breaking at catalytic sites. Interprotein electron transfer addresses the
      potential problem of slow diffusion by designing attractive docking sites that
      permit a conformational search for short tunneling distances.

PMID- 14580558
TI  - Mechanisms of protein fluorophore formation and engineering.
AB  - Green fluorescent protein (GFP) from the jellyfish Aequorea victoria and GFP-like
      proteins from Anthozoa species contain light-absorbing chromophores within their
      protein sequences. Recent studies have made progress in obtaining bright variants
      of these proteins that develop chromophores quickly and efficiently, as well as
      novel fluorescent proteins that photoconvert (i.e. change color upon illumination
      at specific wavelengths). Further molecular characterization of the structure and
      maturation of these proteins is in progress, aimed at providing information for
      rational design of variants with desired fluorescence properties.

PMID- 14580559
TI  - Mechanisms of resistance to antibiotics.
AB  - Microbial resistance to antibiotics is manifested by changes in antibiotic
      permeability, alteration of target molecules, enzymatic degradation of the
      antibiotics, and efflux of antimicrobials from the cytosol. Bacteria and other
      microorganisms use all of these mechanisms to evade the toxic effects of
      antibiotics. Recent research on the molecular aspects of these mechanisms, often
      informed by atomic resolution structures of proteins, enzymes and nucleic acids
      involved in these processes, has deepened our understanding of antibiotic action
      and resistance and, in several cases, spurred the development of strategies to
      overcome resistance in vitro and in vivo.

PMID- 14580560
TI  - Mechanisms of drug/H+ antiport: complete cysteine-scanning mutagenesis and the
      protein engineering approach.
AB  - The notorious difficulty of elucidating structures of membrane transporters by
      crystallography has long prevented our understanding of active transport
      mechanism coupled with ion/proton transport. The determination of the first
      crystal structure of the drug/H+ antiporter AcrB was a breakthrough for structure
      based understanding of drug/H+ antiport. However, although AcrB is a major
      multidrug exporter in Gram-negative organisms, the majority of bacterial drug
      exporters are major facilitator superfamily (MFS) drug transporters. As no
      crystal structures have been solved for MFS transporters, the alternative protein
      engineering methods are still very useful for estimating structures and functions
      of drug/H+ antiporters. This review describes this alternative approach for
      investigating the structure and function of tetracycline/H+ antiporters.

PMID- 14580561
TI  - Protein tyrosine kinases Src and Csk: a tail's tale.
AB  - Csk and Src are two protein tyrosine kinases with similar amino acid sequences
      but very different structures and functions. Csk catalyzes a tail phosphorylation
      reaction on Src and thereby restrains Src's activity and oncogenic potential.
      Comparative analysis of the domain interactions in these enzymes provides a
      lesson in signalling diversity and mechanisms of enzyme regulation. The molecular
      basis of the specificity of Csk targeting the Src tail appears to involve both
      local and long-range interactions and illustrates the complexity of selective
      targeting in post-translational modification.

PMID- 14580562
TI  - Molecular mechanisms of bacterial quorum sensing as a new drug target.
AB  - Bacterial quorum sensing evolved as a means for bacterial communities to rapidly
      and coordinately change genome expression patterns in response to environmental
      cues. Each cell in a community produces and responds to a signaling molecule
      called an autoinducer that serves as an indicator of the population density. A
      high concentration of autoinducer is associated with a large, often confined
      population, which requires altered gene expression for survival. Quorum sensing
      is one mechanism through which a bacterial population receives input from the
      environment and elicits an appropriate response. Because many pathogens require
      quorum sensing to produce virulence factors in response to association with a
      human host, the signaling pathway is a target for design of small-molecule
      inhibitors.

PMID- 14580564
TI  - Microscale separation and analysis.
AB  - There is a recent and growing interest in microscale separation and analysis, a
      result of advantages of miniaturization such as rapid separation times, high
      performance and throughput, reduced costs, and the possibility of system
      integration and multiplexing. Adopting the concepts of conventional capillary
      electrophoresis, capillary electrochromatography, micellar electrokinetic
      chromatography and various sample preparation techniques to microchip format, in
      conjunction with the integration of different analysis steps into a monolithic
      system, have opened new levels in performance, functionality and throughput. This
      review summarizes the recent advances in the field of microfabricated separation
      devices for genomics, proteomics and high-throughput screening applications, also
      addressing system integration and micropreparative functionalities.

PMID- 14580565
TI  - Chemical cytometry.
AB  - Chemical cytometry refers to the use of high-sensitivity analytical tools to
      characterize single cells. These tools include mass spectrometry,
      electrochemistry and capillary separation methods. This review focuses on the use
      of capillary electrophoresis coupled with high-sensitivity detection to
      characterize single cells. In survey experiments, biogenic amines and proteins
      have been characterized in single cells. In directed experiments, fluorescent
      substrates are used to monitor the activity of sets of enzymes, either within a
      family or along an enzymatic cascade. When combined with classical cytometry
      tools, it is now possible to monitor several cellular components in single cells
      as a function of cell cycle, which provides insight into the evolution of
      cellular composition as cells prepare for division.

PMID- 14580566
TI  - Nanoparticles for bioanalysis.
AB  - This review covers the emerging field of nanobiotechnology, in which
      nanoparticles are applied to the analysis of biomolecules. Nanoparticles can be
      used in a variety of bioanalytical formats, and this review discusses four
      classes of use. First, nanoparticles as quantitation tags, such as the optical
      detection of quantum dots and the electrochemical detection of metallic
      nanoparticles. Second, encoded nanoparticles as substrates for multiplexed
      bioassays, such as striped metallic nanoparticles. Third, nanoparticles that
      leverage signal transduction, for example in colloidal gold-based aggregation
      assays. Fourth, functional nanoparticles that exploit specific physical or
      chemical properties of nanoparticles to carry out novel functions, such as the
      catalysis of a biological reaction. In addition, the review discusses the next
      generation of nanoparticles that will be utilized in the life sciences, such as
      nanodots and carbon nanotubes.

PMID- 14580567
TI  - Metabolic oligosaccharide engineering as a tool for glycobiology.
AB  - Oligosaccharides transact information exchange at the cell surface and modulate
      the activities and distribution of proteins within cells. Recently, the ability
      to modify monosaccharide structures within cellular glycans through metabolic
      processes has offered a new avenue for biological studies. The technique of
      metabolic oligosaccharide engineering has been used to disrupt glycan
      biosynthesis, chemically modify cell surfaces, probe metabolic flux inside cells,
      and to identify specific glycoprotein subtypes from the proteome.

PMID- 14580568
TI  - In vivo near-infrared fluorescence imaging.
AB  - Photon penetration into living tissue is highly dependent on the absorption and
      scattering properties of tissue components. The near-infrared region of the
      spectrum offers certain advantages for photon penetration, and both organic and
      inorganic fluorescence contrast agents are now available for chemical conjugation
      to targeting molecules. This review focuses on those parameters that affect image
      signal and background during in vivo imaging with near-infrared light and
      exogenous contrast agents. Recent examples of in vivo near-infrared fluorescence
      imaging of animals and humans are presented, including imaging of normal and
      diseased vasculature, tissue perfusion, protease activity, hydroxyapatite and
      cancer.

PMID- 14580569
TI  - Analysis of protein interactions using fluorescence technologies.
AB  - Biophotonics techniques, especially those involving fluorescence, are widely used
      in proteomics to characterize the in vitro interactions between proteins in high
      throughput mode. On the other hand, fluorescence-based imaging studies often show
      that protein activity is regulated through large protein complexes that
      transiently form at specific sites in the cell. One could therefore argue that a
      systematic functional analysis of the human proteome requires technologies that
      are capable of time and spatially resolved, multiplexed analysis of protein
      interactions within cells.

PMID- 14580570
TI  - Atomic force bio-analytics.
AB  - The atomic force microscope (AFM) allows biomolecules to be observed and
      manipulated under native conditions. It operates in buffer solution, produces
      molecular images with outstanding signal-to-noise ratio, and addresses single
      molecules. Progress in sample preparation and instrumentation has led to
      topographs that reveal sub-nanometer details and surface dynamics of
      biomolecules. Antibodies or oligonucleotides immobilized on cantilevers induce
      bending upon binding of the cognate biomolecule, allowing sub-picomolar
      concentrations to be measured. Biomolecules tethered between support and
      retracting AFM-tip produce force extension curves that reflect the mechanical
      stability of secondary structure elements. Furthermore, multifunctional tips may
      activate single molecules to observe them at work. In all cases, the cantilever
      is critical: its mechanical properties dictate the force-sensitivity and the
      scanning speed.

PMID- 14580571
TI  - Metabonomics: NMR spectroscopy and pattern recognition analysis of body fluids
      and tissues for characterisation of xenobiotic toxicity and disease diagnosis.
AB  - Global profiling tools are required to fully understand the impact of genetic
      modifications and toxicological interventions on the network of transcripts,
      proteins and metabolites found within a cell, tissue or organism. High-resolution
      1H NMR spectroscopy in conjunction with statistical pattern recognition is one
      such technique, referred to as metabonomics or metabolomics, which is
      increasingly being used to globally profile metabolites. This review examines
      analytical advances in NMR spectroscopy that have aided this development
      including high-resolution magic angle spinning NMR spectroscopy, cryogenically
      cooled probes and high-through put systems. This has allowed the approach to
      identify genetically modified yeast strains and distinguish both disease presence
      and severity in coronary heart disease.

PMID- 14580573
TI  - Metabolic engineering for the microbial production of 1,3-propanediol.
AB  - Improvements in the biological production of 1,3-propanediol, a key component of
      an emerging polymer business, have been realized. Utilizing genes from natural
      strains that produce 1,3-propanediol from glycerol, metabolic engineering has
      enabled the development of a recombinant strain that utilizes the lower cost
      feedstock D-glucose. This accomplishment bodes well for future metabolic
      engineering efforts and, ultimately, for increased societal benefit obtained
      through the production of chemicals from renewable resources.

PMID- 14580574
TI  - Dynamic modeling of microbial cell populations.
AB  - Microbial cultures are comprised of heterogeneous cells that differ according to
      their size and intracellular concentrations of DNA, proteins and other
      constituents. Recent advances have been made in cell population modeling, which
      allow the effects of cell heterogeneity on culture dynamics and metabolite
      production to be predicted. If the intracellular state can be captured with a few
      variables, the population balance equation framework is a viable modeling
      approach. The cell ensemble modeling technique is better suited for the
      development of population models that include more detailed descriptions of
      cellular metabolism and/or cell-cycle progression.

PMID- 14580575
TI  - Bioreactor state estimation and control.
AB  - Advanced control methods have been effectively employed for industrial chemical
      processing for decades. Only recently, however, have model-based strategies been
      implemented for biological processes. Some notable advances include the
      enhancement of metabolic flux models to describe the dynamic behavior observed in
      biochemical reactors. The combination of more than one type of model in a hybrid
      form was shown to perform well for bioprocess control applications.

PMID- 14580576
TI  - Process design for microbial plastic factories: metabolic engineering of
      polyhydroxyalkanoates.
AB  - Implementing several metabolic engineering strategies, either individually or in
      combination, it is possible to construct microbial plastic factories to produce a
      variety of polyhydroxyalkanoate (PHA) biopolymers with desirable structures and
      material properties. Approaches include external substrate manipulation,
      inhibitor addition, recombinant gene expression, host cell genome manipulation
      and, most recently, protein engineering of PHA biosynthetic enzymes. In addition,
      mathematical models and molecular methods can be used to elucidate metabolically
      engineered systems and to identify targets for performance improvement.

PMID- 14580577
TI  - Enabling inverse metabolic engineering through genomics.
AB  - Inverse metabolic engineering (IME) is a powerful framework for engineering
      cellular phenotypes. Progress in this field has been limited by a lack of
      comprehensive methods for efficiently identifying the genetic basis of relevant
      phenotypes. Advances in genomics technologies, including DNA microarrays and gene
      sequencing, have dramatically improved our ability to relate changes in phenotype
      with associated changes in genotype. When applied in the context of IME, these
      tools should enable the integration of "evolutionary" and "direct" approaches to
      engineering cell physiology, which should improve our understanding of the
      complex interactions affecting the expression, evolution and engineering of
      traits in natural and industrial hosts.

PMID- 14580578
TI  - Advances in flux balance analysis.
AB  - Biology is going through a paradigm shift from reductionist to holistic, systems
      based approaches. The complete genome sequence for a number of organisms is
      available and the analysis of genome sequence data is proving very useful. Thus,
      genome sequencing projects and bioinformatic analyses are leading to a complete
      'parts catalog' of the molecular components in many organisms. The next challenge
      will be to reconstruct and simulate overall cellular functions based on the
      extensive reductionist information. Recent advances have been made in the area of
      flux balance analysis, a mathematical modeling approach often utilized by
      metabolic engineers to quantitatively simulate microbial metabolism.

PMID- 14580579
TI  - Microfluidic separation of DNA.
AB  - DNA separation is important for numerous applications in biotechnology and
      medicine. Efforts to improve DNA separation in microdevices have led to advances
      in capillary electrophoresis and the development of novel separation strategies.
      Current research on microcapillary electrophoresis materials is focused on the
      development of separation matrices with low injection viscosities and wall
      coating capabilities. Microcapillary injector geometries are being designed to
      allow increased control of sample plug volumes. Novel separation strategies using
      entropic traps, arrays of pillars and Brownian ratchets are also being developed.

PMID- 14580580
TI  - Antisense technology in molecular and cellular bioengineering.
AB  - Antisense technology is finding increasing application not only in clinical
      development, but also for cellular engineering. Several types of antisense
      methods (e.g. antisense oligonucleotides, antisense RNA and small interfering
      RNA) can be used to inhibit the expression of a target gene. These antisense
      methods are being used as part of metabolic engineering strategies to
      downregulate enzymes controlling undesired pathways with regard to product
      formation. In addition, they are beginning to be utilized to control cell
      phenotype in tissue engineering constructs. As improved methods for antisense
      effects that can be externally regulated emerge, these approaches are likely to
      find increased application in cellular engineering applications.

PMID- 14580581
TI  - Measurements of protein self-association as a guide to crystallization.
AB  - The challenge of crystallizing proteins has led to a significant amount of
      research in understanding protein self-association and assembly. Arguably the
      most influential finding in this field in the past decade has been that weakly
      attractive protein interactions, characterized in terms of the osmotic second
      virial coefficient, correlate with solution conditions that are conducive to
      crystallization. Recent work in this area has focused on the development of more
      efficient techniques for measuring the second virial coefficient, as traditional
      characterization methods suffer from poor efficiency in terms of time and protein
      consumption. The resulting measurements have provided new insights into patterns
      of protein interactions and their relation to protein phase behavior.

PMID- 14580582
TI  - Tissue and cell engineering.

PMID- 14580583
TI  - Controlling skin morphogenesis: hope and despair.
AB  - To master tissue and organ morphogenesis necessitates a thorough understanding of
      the cellular and molecular events involved in development, renewal, repair and
      regeneration. Skin reconstruction is the paradigm of tissue engineering. The
      transplantation of autologous adult epidermal stem cells is a life-saving
      procedure as it regenerates the indispensable barrier function of the skin, but
      the reconstruction of fully functional skin has been hampered by the complexity
      of the process. The recent identification of multipotent epithelial stem cells in
      adult hair follicles and of multipotent stem cells in dermis raises new hopes.

PMID- 14580584
TI  - Role of the extracellular matrix in morphogenesis.
AB  - The extracellular matrix is a complex, dynamic and critical component of all
      tissues. It functions as a scaffold for tissue morphogenesis, provides cues for
      cell proliferation and differentiation, promotes the maintenance of
      differentiated tissues and enhances the repair response after injury. Various
      amounts and types of collagens, adhesion molecules, proteoglycans, growth factors
      and cytokines or chemokines are present in the tissue- and temporal-specific
      extracellular matrices. Tissue morphogenesis is mediated by multiple
      extracellular matrix components and by multiple active sites on some of these
      components. Biologically active extracellular matrix components may have use in
      tissue repair, regeneration and engineering, and in programming stem cells for
      tissue replacement.

PMID- 14580585
TI  - Fibroblast growth factors: key players in epithelial morphogenesis, repair and
      cytoprotection.
AB  - Fibroblast growth factors (FGFs) regulate early development and organogenesis. In
      particular, a subfamily of FGFs is essential for the formation and
      differentiation of epithelial tissues and organs. Recent studies revealed a
      crucial role for these FGFs in repair of the skin, intestine and liver. In
      addition, the cytoprotective potential of FGFs suggests their use for the
      protection of epithelial cells under conditions of stress in vivo. Indeed, the
      first successful clinical trials using FGFs for the treatment of radiation- and
      chemotherapy-induced mucosal epithelial damage have been announced.

PMID- 14580586
TI  - Mechanisms of force generation and transmission by myofibroblasts.
AB  - The myofibroblast has been shown to have a key role in tissue reconstruction
      after injury and pathological changes characterized by fibrosis. Force generation
      by the myofibroblast depends on the isometric contraction of stress fibers
      containing alpha-smooth muscle actin, and is mediated through Rho/Rho-kinase. The
      force is transmitted by vinculin and tensin-containing "supermature" focal
      adhesions, which connect stress fibers with the extracellular matrix. Force
      production and transmission by the myofibroblast are modulated by the coordinated
      action of cytokines, extracellular matrix components and mechanical tension.
      Regulation of these phenomena will be important for therapeutic strategies aimed
      at influencing fibrocontractive diseases.

PMID- 14580587
TI  - Signaling in morphogenesis: transport cues in morphogenesis.
AB  - Extracellular transport processes play critical roles in morphogenesis. While
      diffusive transport effects on morphogenesis are well illustrated in examples
      like blood capillary architecture and in cell morphogenetic responses to the
      local extracellular protein environment, the effects of fluid convection,
      although important in many developing and regenerating tissues, are not well
      understood. Convective forces are present whenever a hydrated tissue undergoes
      dynamic mechanical strain, and so convection could not only dominate the
      transport of large molecules like proteins, but might also serve as a mechanism
      for mechanosensing. The complex interdependence of mechanical forces, protein
      transport and extracellular morphogen gradients needs to be elucidated in a
      comprehensive way in order for the importance of transport on morphogenesis to be
      fully appreciated.

PMID- 14580588
TI  - Materials as morphogenetic guides in tissue engineering.
AB  - Within native tissues cells are held within the extracellular matrix (ECM), which
      has a role in maintaining homeostasis, guiding development and directing
      regeneration. Efforts in tissue engineering have aimed to mimick the ECM to help
      guide morphogenesis and tissue repair. Studies have not only looked at ways to
      mimick the structure and characteristics of the ECM, but have also considered
      ways to reproduce its molecular properties including its bioadhesive character,
      proteolytic susceptibility and ability to bind growth factors.

PMID- 14580589
TI  - Protein-based signaling systems in tissue engineering.
AB  - Tissue engineering aims to replace damaged tissues or organs using either
      transplanted cells or host cells recruited to the target site. Protein signaling
      is crucial to regulate cell phenotype and thus engineered tissue structure and
      function. Biomaterial vehicles are being designed to incorporate and locally
      deliver various molecules involved in this signaling, including both growth
      factors and peptides that mimick whole proteins. Controlling the concentration,
      local duration and spatial distribution of these factors is key to their utility
      and efficacy. Recent advances have been made in the development of polymeric
      delivery systems intended to achieve this control.

PMID- 14580590
TI  - The thermal history of human fossils and the likelihood of successful DNA
      amplification.
AB  - Recent success in the amplification of ancient DNA (aDNA) from fossil humans has
      led to calls for further tests to be carried out on similar material. However,
      there has been little systematic research on the survival of DNA in the fossil
      record, even though the environment of the fossil is known to be of paramount
      importance for the survival of biomolecules over archaeological and geological
      timescales. A better understanding of aDNA survival would enable research to
      focus on material with greater chances of successful amplification, thus
      preventing the unnecessary loss of material and valuable researcher time. We
      argue that the thermal history of a fossil is a key parameter for the survival of
      biomolecules. The thermal history of a number of northwest European Neanderthal
      cave sites is reconstructed here and they are ranked in terms of the relative
      likelihood of aDNA survival at the sites, under the assumption that DNA
      depurination is the principal mechanism of degradation. The claims of aDNA
      amplification from material found at Lake Mungo, Australia, are also considered
      in the light of the thermal history of this site.

PMID- 14580591
TI  - Later Middle Pleistocene human remains from the Almonda Karstic system, Torres
      Novas, Portugal.
AB  - Later Middle Pleistocene archeological deposits of the Galeria Pesada (Gruta da
      Aroeira), Almonda Karstic System, Torres Novas, Portugal, yielded two archaic
      human teeth, a mandibular canine and a maxillary third molar. The C(1)presents
      moderate and asymmetrical shoveling with a stout root. The slightly worn
      M(3)exhibits at least four cusps with a large hypocone, three roots with large
      radicular plates, and an absence of taurodontism. They are moderately large for
      later Middle Pleistocene humans in their buccolingual crown diameters, although
      the M(3)mesiodistal diameter is modest. The C(1)exhibits labial calculus and
      multiple linear hypoplastic defects, but the M(3)is lesion free. Both teeth are
      morphologically similar to those of other Middle Pleistocene European humans and
      reinforce a pattern of dental hypertrophy among these archaic Homo.

PMID- 14580592
TI  - The super-eruption of Toba, did it cause a human bottleneck?

PMID- 14580593
TI  - Did the super-eruption of Toba cause a human population bottleneck? Reply to
      Gathorne-Hardy and Harcourt-Smith.

PMID- 14580594
TI  - More is not always better: Trotter and Gleser's equations and stature estimates
      of Upper Paleolithic European samples.

PMID- 14580595
TI  - Early modern human cranial remains from the Pestera cu Oase, Romania.

PMID- 14580596
TI  - Homo erectus, Homo ergaster, Homo "cepranensis," and the Daka cranium.

PMID- 14580597
TI  - Interleaving TMS with functional MRI: now that it is technically feasible how
      should it be used?

PMID- 14580598
TI  - Clinical aspects and pathophysiology of narcolepsy.
AB  - Narcolepsy is a chronic debilitating sleep disorder first described in the late
      19th century. It is characterized by two major symptoms, excessive daytime
      sleepiness and cataplexy, and two so-called auxiliary symptoms, hypnagogic
      hallucinations and sleep paralysis. The final diagnosis relies on polysomnography
      showing the presence of sleep onset rapid eye movement periods (SOREMPs) during
      the multiple sleep latency test. The presence of HLA DQA1*0102-DQB1*0602 is
      supportive of the diagnosis. The pathophysiology of the disorder is still unknown
      but an imbalance between monoamines and acetylcholine is generally accepted.
      Recent findings in narcoleptic dogs, a natural model of narcolepsy, and in
      knockout mice revealed that a mutation of type 2 hypocretin receptor plays a
      major role in the etiology of narcolepsy. Up to now, no mutation has been found
      in humans except a case of early onset and atypical narcolepsy. However, a marked
      reduction of hypocretin type 1 has been found in the cerebrospinal fluid (CSF) of
      a majority of patients and a global loss of hypocretins was noted in post-mortem
      brain tissue of narcoleptic subjects. Conversely, no hypocretin neuron
      degeneration has been observed in the genetic form of narcolepsy in dogs but no
      trace of hypocretin was seen in the brain or the CSF in cases of sporadic canine
      narcolepsy. This suggests that different hypocretinergic mechanisms are involved
      in sporadic and genetic forms of canine narcolepsy. Treatment has not evolved
      significantly over the last few years. However, new drugs, such as hypocretin
      agonists, are currently being developed. SIGNIFICANCE: After the discovery of the
      type 2 hypocretin receptor mutation in canine narcolepsy and the finding of a CSF
      hypocretin-1 deficiency in human narcolepsy, the major stream of research has
      involved the hypocretinergic system. However, other lines of research deserve to
      be pursued simultaneously, in view of comprehensive advancements in the
      understanding of narcolepsy.

PMID- 14580599
TI  - The effects of alteration of effector and side of movement on the contingent
      negative variation.
AB  - OBJECTIVE: The contingent negative variation (CNV) is a widespread
      electroencephalographic (EEG) potential that occurs during the interval between a
      warning stimulus and a subsequent imperative stimulus if a mental or motor
      response is required. The present study was designed to explore the impact of the
      previous trial on the CNV of the forthcoming trial, that is, how a previous
      movement affects brain activation preparing the next movement. Effects of
      alteration of finger (from index to middle, and vice versa) and hand (from left
      to right, and vice versa) were examined independently from each other. METHODS:
      CNV was recorded in 20 right-handed healthy subjects with electrodes placed at
      F7, F5, F3, F4, F6, F8, FC5, FC3, FC1, FC2, FC4, FC6, T7, C5, C3, C1, C2, C4, C6,
      T8, CP5, CP1, CP2, CP6, P7, P3, P4 and P8. In a visual/visual S1-choice paradigm,
      an earlier informative (S1) stimulus which instructed for side and finger of the
      following movement was followed 3 s later by an imperative (S2) stimulus
      providing the command to move. Subjects had to respond to each imperative
      stimulus with an appropriate button press made by brisk flexion movements with
      the index or middle finger of each hand. The CNV recorded in the interval between
      the informative and the imperative stimulus was analysed with respect to finger
      and hand of the present and the preceding movement. RESULTS/CONCLUSIONS: (1) A
      change of the side of movement is associated with a widespread increase of
      negativity contralateral to the currently prepared movement. (2) A change of
      finger is associated with a focal increase of negativity contralateral to the
      side of the current movement over temporoparietal and mid-parietal areas. (3) A
      change of finger results in a widespread increase of negativity over the left
      hemisphere.

PMID- 14580600
TI  - Increased rate of P300 latency prolongation with age in drug-naive and first
      episode schizophrenia.
AB  - OBJECTIVE: Previous studies have found an increased rate of P300 latency
      prolongation with age in medicated chronic patients with schizophrenia,
      suggesting a pathological neurodegenerative process. In this study, we
      investigated whether this abnormality was identified in drug-naive and first
      episode patients with schizophrenia. METHODS: P300 from auditory stimuli was
      recorded from 20 drug naive and first episode male patients with schizophrenia
      and compared with 23 age and handedness matched healthy male controls. The
      relationship of P300 latency and P300 amplitude to age in each group was
      evaluated using polynomial regression analyses. RESULTS: Reduction of P300
      amplitude was significant in drug-naive and first episode schizophrenia patients.
      P300 amplitude negatively correlated with age in schizophrenia patients but not
      in controls. Although the prolongation of P300 latency with age was observed in
      both groups, the regression slope for P300 latency with age was significantly
      steeper in patients with schizophrenia than in normal controls. Significant
      overall curvilinear correlations with age were also found for P300 latency and
      amplitude in patients with schizophrenia, and for P300 latency in normal
      controls. CONCLUSIONS: The greater increase in P300 latency and reduction in P300
      amplitude with age may be a primary neuropathological effect of schizophrenia.
      SIGNIFICANCE: This study suggests that neurodegenerative processes are involved
      in the etiology of schizophrenia.

PMID- 14580601
TI  - Disturbed transcallosally mediated motor inhibition in children with attention
      deficit hyperactivity disorder (ADHD).
AB  - OBJECTIVE: The aim of this study was to investigate mechanisms of motor-cortical
      excitability and inhibition which may contribute to motor hyperactivity in
      children with attention deficit hyperactivity disorder (ADHD). METHODS: Using
      transcranial magnetic stimulation (TMS), involvement of the motor cortex and the
      corpus callosum was analysed in 13 children with ADHD and 13 sex- and age-matched
      controls. Contralateral silent period (cSP) and transcallosally mediated
      ipsilateral silent period (iSP) were investigated. RESULTS: Resting motor
      threshold (RMT), amplitudes of motor evoked potentials (MEP) and cSP were similar
      in both groups whereas iSP-latencies were significantly longer (p<0.05) and their
      duration shorter (p<0.01) in the ADHD group. For the ADHD group iSP duration
      tended to increase and iSP latency to decrease with age (n.s.). Conners-Scores
      did neither correlate with iSP-latencies and -duration nor with children's age.
      CONCLUSIONS: The shortened duration of iSP in ADHD children could be explained by
      an imbalance of inhibitory and excitatory drive on the neuronal network between
      cortex layer III-the projection site of transcallosal motor-cortical fibers-and
      layer V, the origin of the pyramidal tract. The longer iSP-latencies might be the
      result of defective myelination of fast conducting transcallosal fibers in ADHD.
      iSP may be a useful supplementary diagnostic tool to discriminate between ADHD
      and normal children.

PMID- 14580602
TI  - Chronic schizophrenics with positive symptomatology have shortened EEG microstate
      durations.
AB  - OBJECTIVE: In young, first-episode, never-treated schizophrenics compared with
      controls, (a) generally shorter durations of EEG microstates were reported
      (Koukkou et al., Brain Topogr 6 (1994) 251; Kinoshita et al., Psychiatry Res
      Neuroimaging 83 (1998) 58), and (b) specifically, shorter duration of a
      particular class of microstates (Koenig et al., Eur Arch Psychiatry Clin Neurosci
      249 (1999) 205). We now examined whether older, chronic schizophrenic patients
      with positive symptomatology also show these characteristics. METHODS:
      Multichannel resting EEG (62.2 s/subject) from two subject groups, 14 patients
      (36.1+/-10.2 years old) and 13 controls (35.1+/-8.2 years old), all males, was
      analyzed into microstates using a global approach for microstate analysis that
      clustered the microstates into 4 classes (Koenig et al., 1999). RESULTS: (a)
      Hypothesis testing of general microstate shortening supported a trend (P=0.064).
      (b) Two-way repeated measure ANOVA (two subject groupsx4 microstate classes)
      showed a significant group effect for microstate duration. Posthoc tests revealed
      that a microstate class with brain electric field orientation from left central
      to right central-posterior had significantly shorter microstates in patients than
      controls (68.5 vs. 76.1 ms, P=0.034). CONCLUSIONS: The results were in line with
      the results from young, never-treated, productive patients, thus suggesting that
      in schizophrenic information processing, one class of mental operations might
      intermittently cause deviant mental constructs because of premature termination
      of processing.

PMID- 14580603
TI  - Source distribution of neuromagnetic slow wave activity in schizophrenic and
      depressive patients.
AB  - OBJECTIVE: Focal slow waves in the delta and theta frequency range frequently
      appear in psychopathological conditions. Due to their focal nature they can be
      localized by dipole modeling. We previously reported regional clustering of slow
      waves in temporal and parietal cortex of schizophrenic patients whereas such
      activity is largely absent in normals. Here we examine, to what extent
      distribution of slow wave generators differentiates schizophrenic from depressive
      syndromes. METHODS: The regional densities of generators of focal slow waves were
      determined during resting conditions in patients with DSM-IV diagnoses of
      schizophrenia (N=25) and depression (N=27) and in 18 healthy controls. RESULTS:
      Schizophrenic patients demonstrated accentuated temporal and parietal delta and
      theta dipole clustering, when compared to both the control and the depressive
      sample. In contrast, depressive patients had reduced frontal and prefrontal delta
      and theta dipole density relative to both schizophrenics and controls. This
      pattern was not related to age. Men generally displayed somewhat higher slow wave
      activity than women. For the areas of most pronounced slow wave deviances
      activity within each group was related to symptom scores: higher left-temporal
      slow wave activity was associated with hallucinations in schizophrenics,
      suppression of left-prefrontal slow wave activity correlated with depression
      scores. CONCLUSIONS: Results suggest that slow wave distribution may assist in
      differentially diagnosing psychopathological conditions.

PMID- 14580604
TI  - Association between reduced duration mismatch negativity (MMN) and raised
      temporal discrimination thresholds in schizophrenia.
AB  - OBJECTIVE: The event-related potential known as mismatch negativity (MMN) is
      elicited whenever the auditory system detects a change against an invariant
      background of stimulation. A reduction in mismatch negativity is well established
      in schizophrenia. The present study explored the association between reduced
      duration mismatch negativity in schizophrenia and behavioural measures of
      temporal discrimination. METHOD: Mismatch negativity amplitude to duration
      increments (125 vs. 50 ms) was compared between individuals with schizophrenia
      and healthy controls. Mismatch negativity amplitude was also related to two
      behavioural measures of temporal discrimination (silent and filled intervals) for
      detecting changes in stimuli of similar duration. RESULTS: Patients produced
      higher discrimination threshold estimates and smaller amplitude mismatch
      negativity responses to temporally deviant stimuli. Temporal discrimination
      thresholds correlated with the amplitude of the phase reversal in mismatch
      negativity at the left mastoid such that patients who produced the highest
      thresholds produced the smallest mismatch response. CONCLUSIONS: Imprecise
      representations of the temporal properties of auditory stimuli can account for
      some of the reduction in mismatch negativity amplitude in some patients but
      additional factors clearly contribute. The results suggest that patients who do
      and do not exhibit temporal processing deficits on behavioural tasks produce
      different patterns of reduction in duration mismatch negativity.

PMID- 14580605
TI  - Effects of single-pulse transcranial magnetic stimulation (TMS) on functional
      brain activity: a combined event-related TMS and evoked potential study.
AB  - OBJECTIVE: To further evaluate the potential of slew-rate limiting amplifiers to
      record electrophysiological signals in spite of concurrent transcranial magnetic
      stimulation (TMS), and to explore the effects of single-pulse TMS on
      electroencephalographic (EEG) correlates of functional brain activity. METHODS:
      Visual-evoked potentials (VEPs) to checkerboards were recorded in 7 right-handed
      subjects, while single-pulse TMS was applied to the occipital pole either at
      visual stimulus onset, during the build-up or at the expected peak of the early
      VEP component P1 (VIS&TMS). Timing of TMS was individually adjusted based on each
      subject's VEP-latency. A condition of TMS without concurrent visual stimulation
      (TMS(alone)) served for subtraction purposes (VIS&TMS minus TMS(alone)) to
      partial out TMS-related contaminations of the EEG signal. RESULTS: When TMS was
      applied at visual stimulus onset, VEPs (as calculated by subtraction) perfectly
      matched control VEPs to visual stimulation alone. TMS at around P1, in contrast,
      modified the targeted (P1) and the subsequent VEP component (N1), independently
      of whether TMS was given at build-up or peak. CONCLUSIONS: The retrieval of
      regular VEPs with concomitant TMS at visual stimulus onset suggests that the
      employed EEG system and subtraction procedure are suited for combined EEG-TMS
      studies. The VEP changes following TMS at around P1 provide direct clues on the
      temporal dynamics of TMS pulse effects on functional activity in the human brain.
      Our data suggest effects of relatively long duration (approximately 100 ms) when
      TMS is applied while functional neuronal activity evolves.

PMID- 14580606
TI  - Abnormal CNV in chronic heavy drinkers.
AB  - OBJECTIVE: We used the contingent negative variation (CNV), a slow negative shift
      in the human electroencephalogram, to investigate the effects of heavy chronic
      alcohol use on frontal lobe function. METHODS: Event-related potentials (ERPs)
      were recorded from 30 heavy drinkers (HD) and 30 age-, sex-, and education
      matched light or non-drinkers (LD), using a classical two-stimulus reaction time
      (RT) paradigm. Structural magnetic resonance images and neuropsychological tests
      were also administered. RESULTS: The amplitude of the late CNV was significantly
      reduced in HD relative to light drinkers. Moreover, diminished CNV amplitudes in
      HD appear to be closely related to the amount of recent alcohol consumption.
      There were no significant differences in neuropsychological measures of frontal
      lobe function and frontal lobe volume between light and HD. However, in HD,
      reduced late CNV amplitudes were associated with decreased frontal lobe gray
      matter volume and poor performance on the Trail Making Test B. In LD but not in
      HD, late CNV amplitude correlated positively with RT, suggesting that the late
      CNV reflects some aspect of motor and cognitive preparation. CONCLUSIONS: The
      inverse relationships between frontal lobe gray matter volume, performance on the
      Trail Making Test B, and late CNV amplitude in HD suggest that the ERP
      abnormalities observed in the current study may be indices of alcohol-related
      damage to the frontal lobe. The lack of a significant relationship between CNV
      amplitude and RT in HD suggests that chronic heavy alcohol use may disrupt
      response preparation.

PMID- 14580607
TI  - A whole head MEG study of the amplitude-modulation-following response: phase
      coherence, group delay and dipole source analysis.
AB  - OBJECTIVE: The amplitude-modulation-following response (AMFR) is the frequency
      component detectable in the electroencephalogram (EEG) or magnetoencephalography
      (MEG) corresponding to the modulation frequency of an amplitude modulated tone
      used as a continuous acoustic stimulus. Various properties of the AMFR depend on
      modulation frequency, suggesting that different generators along the auditory
      pathway are involved. The present study addresses these issues on the basis of a
      whole head MEG experiment. METHODS: AM tones with modulators in the 40 Hz and 80
      Hz range were presented unilaterally to 10 normal hearing subjects. Biomagnetic
      responses were recorded with a 151 channel MEG system. The data analysis
      concentrated on the phase coherence of the responses, group delays and the
      estimated location of underlying equivalent dipole sources. RESULTS: MEG AMFR is
      more reliably detected in the 40 Hz than in the 80 Hz range. Both response
      amplitude and phase coherence indicate clear bilateral activation over the
      parietal/temporal region. Dipole source analysis confirms that sources are
      located in or near the auditory cortex. Group delays at 80 Hz are shorter than at
      40 Hz. CONCLUSIONS: In both modulation frequency ranges MEG responses are
      dominated by activity in the auditory cortex, in apparent contrast with EEG data
      in the literature, pointing to dominant contributions of thalamic sources to the
      80 Hz AMFR.

PMID- 14580608
TI  - Muscle afferent inputs from the hand activate human cerebellum sequentially
      through parallel and climbing fiber systems.
AB  - OBJECTIVE: Spatio-temporal response characteristics of the human cerebellum to
      median nerve stimulation (MNS) were studied with the use of a whole-head
      magnetoencephalographic (MEG) system covering the cerebellum and upper cervical
      spine. METHODS: Neuromagnetic responses from the cerebellum were recorded
      following electric stimulation of the right median nerve in 12 subjects. In 6 out
      of 12 subjects, the responses to the left median nerve and to the right index or
      middle finger stimulation were also recorded. RESULTS: The medial part of the
      cerebellum (spinocerebellum) was activated by MNS. In contrast, there were no
      responses from the cerebellum to the finger stimulation, suggesting that muscle
      afferent inputs are the source of cerebellar activation for MNS. The cerebellar
      responses consisted of 3 or 4 components of alternating polarity within 90 ms
      post-stimulus: the current direction for the first component was from the depth
      to the surface of the anterior lobe. CONCLUSIONS: From the timing and current
      direction, we speculate that the 4 components reflect, respectively, (1)
      excitatory postsynaptic potentials (EPSPs) of granule cells, (2) Purkinje cell
      EPSPs at the distal dendrites driven by parallel fibers, (3) Purkinje cell EPSPs
      at the soma and the proximal dendrites mediated by climbing fibers and (4) second
      Purkinje cell EPSPs at the distal dendrites driven by parallel fibers.
      SIGNIFICANCE: We first visualized serial activation of the human spinocerebellum
      following MNS noninvasively with MEG.

PMID- 14580609
TI  - Tactile interference to the face affects magnetic responses elicited by electric
      thumb stimulation.
AB  - OBJECTIVE: We examined the effect of tactile interference to the face on
      somatosensory evoked magnetic fields (SEFs) following electric thumb stimulation.
      METHODS: SEFs were elicited by electric stimulation of the right thumb in a
      control and two interference conditions. In the interference conditions,
      continuous tactile stimuli were delivered to the skin surface over the right
      upper face or the right thumb. RESULTS: The face interference significantly
      attenuated N20m and enhanced P30m. The amplitudes of N20m in the face and thumb
      interference conditions were 90.3 and 70.3% of the value in the control
      condition, respectively, while those of P30m were 120.2 and 74.4%. CONCLUSIONS:
      In human somatosensory area 3b, the representation of the thumb is immediately
      adjacent to that of the face although the thumb and face are physically distant.
      We suggest, therefore, that the effect of tactile interference on N20m depends on
      a cortical distance between electrically and mechanically activated 3b areas,
      rather than a physical distance between the body parts to which these two stimuli
      were administered. Although it is unclear why the face interference specifically
      enhanced the P30m, it is suggested that the generating mechanism of the
      interference effect on P30m may be different from that on N20m. SIGNIFICANCE: The
      tactile interference effect on N20m does not depend on the physical distance
      between electrically and mechanically activated skin areas, but on the distance
      of the 3b cortex receiving these two inputs.

PMID- 14580610
TI  - The effects of different levels of all-rac- and RRR-alpha-tocopheryl acetate
      (vitamin E) on visual function in rats.
AB  - OBJECTIVE: A rat model of vitamin E (alpha-tocopherol) deficiency with similar
      "clinical", electrophysiological and neuropathological abnormalities to that seen
      in man was used to investigate the effects of various dietary intakes of
      synthetic (all-rac-) and natural (RRR-) alpha-tocopheryl acetate (alphaTA) on
      visual function. METHODS: Longitudinal measurements of the electroretinogram
      (ERG) and visual evoked potentials (VEPs) were made monthly for 14 months in 9
      groups of rats (n=12/group) receiving different amounts and types of alphaTA. The
      animals were then killed for biochemical analyses. RESULTS: (1) The first
      significant abnormalities of both the ERG and VEP were found after 8 months of
      deficiency. (2) A diet containing 1.25 mg/kg of alphaTA provided marginal
      protection. (3) The biological activity of all-rac- was approximately 75% of RRR
      alphaTA. (4) The concentration of free malondialdehyde (a measure of lipid
      peroxidation) was significantly increased in all tissues, including the eye, from
      deficient compared to control rats. CONCLUSIONS: These results are consistent
      with alpha-tocopherol deficiency causing increased lipid peroxidation leading to
      abnormal visual function but could also be explained by more specific but
      undefined function(s) of alpha-tocopherol in the eye.

PMID- 14580611
TI  - Vector analysis of visual evoked potentials in migraineurs with visual aura.
AB  - OBJECTIVE: To assess the capability of vector analysis of visual evoked
      potentials (VEPs) for revealing alterations in posterior visual pathways in
      migraineurs with visual aura. METHODS: VEPs to pattern reversal (PR) and LED
      goggle stimulation were obtained in 23 patients suffering from migraine with
      visual aura, in an orthogonal Fpz-Oz and T3-T4 montage and displayed as a two
      channel Lissajous' trajectory. VEP latency and amplitude at Fpz-Oz, bc segment
      amplitude (V) and bc vector orientation angle (theta) were compared with a
      previously collected normative database for individual assessment, and group
      comparisons with the previously collected normal sample were made.
      Electrophysiological measures were also correlated with time from onset of
      disease and from the last crisis, and with the side of symptoms. RESULTS: No
      individual alterations in VEP latency or amplitude were observed. However, 36.4%
      of patients showed alterations in vector orientation to PR and 78% to LED
      goggles. Group differences with respect to normal subjects were found not only in
      vector orientation but also in midline VEP and V, only for PR stimulation. A
      significant relationship was found between the laterality of vector deviation and
      the laterality of symptoms. CONCLUSIONS: Vector analysis of VEP revealed
      alterations possibly corresponding to asymmetrical visual cortex activation in
      migraineurs with visual aura, mainly to diffuse light stimulation. SIGNIFICANCE:
      An electrophysiological parameter of individual value for revealing asymmetric
      activation of visual cortex in migraineurs is proposed.

PMID- 14580612
TI  - First night effect in children and adolescents undergoing polysomnography for
      sleep-disordered breathing.
AB  - OBJECTIVE: To establish whether there is a first night effect (FNE) in children
      and adolescents with suspected obstructive sleep apnoea undergoing
      polysomnography (PSG) and whether this affects sleep and breathing, furthermore,
      to determine the extent to which age may influence the sleep and
      cardiorespiratory parameters. METHODS: One hundred and thirty-one children and
      adolescents (age classes-A: 2-6 years n=37; B: 7-12 years n=60; C: 13-17 years
      n=34) underwent PSG on 2 consecutive nights (I and II) under identical conditions
      for suspected sleep-related respiratory disorders. One hundred and five patients
      including 3 patients with obstructive sleep apnoea syndrome (OSAS) treated by
      adenotonsillectomy and 18 OSAS patients receiving nCPAP-therapy had no PSG
      abnormalities (Group 1-A: n=28; B: n=53; C: n=24). A further 26 patients (Group
      2) had clinically and polysomnographically confirmed untreated OSAS (A: n=9; B:
      n=12; C: n=5). RESULTS: There were no statistically significant differences
      between children with no PSG-abnormalities (Group 1) and those with OSAS (Group
      2) in terms of sleep parameters (arousal indices excluded), oxygen saturation
      (SaO(2)) and heart rate (HR), and these parameters have, therefore, been pooled
      for the entire group (n=131) in the 3 age classes A, B and C. In the second and
      third age classes, sleep efficiency on the first night was reduced. In all age
      classes, there was significantly more wakefulness during the first night. In the
      second and third age ranges, the proportion of NREM 1 in the first night was
      significantly higher, with a correspondingly reduced proportion of NREM 4 in the
      third age group. In all age classes, REM sleep was significantly less during the
      first night, but REM latency was comparable on both nights. On the first night,
      the mean HR was higher. There were significant differences in apnoea/hypopnoea
      index (AHI), electroencephalogram (EEG)-arousal-index (AI) and motoric arousal
      index (jerk index, JI) between Groups 1 and 2. In neither group, were there any
      significant differences in AHI, mean SaO(2) or number of EEG-arousals between
      nights 1 and 2. Only in the age class A, in Group 2 (n=9) was the number of
      motoric arousals significantly higher on the first night. Comparison of the age
      classes A, B, and C revealed that most polysomnographic parameters were age
      dependent. Increasing age was found to correlate with a higher proportion of NREM
      1, especially on the first night. Also, there was an age-dependent increase in
      NREM 2 on both nights, a decrease in NREM 3 on the first night, and a decrease in
      NREM 4 on both nights. In older children, we also found a lower proportion of REM
      sleep on the first night and a lower HR on both nights. In Group 1, we found a
      lowered AHI, AI and JI (for JI significant only on the first night) in older
      patients. No such age dependence of AHI, AI and JI was seen in OSAS patients
      (Group 2). CONCLUSIONS: In children and adolescents, there is an FNE comparable
      with that described in adults. In OSAS children and also in children with no PSG
      abnormalities, there is night-to-night-variability in sleep parameters, but not
      in respiratory parameters. An adaptation night is, therefore, necessary when
      sleep architecture is to be studied, but not when only the nocturnal respiratory
      pattern is investigated. Sleep parameters, HR and arousal indices are all age
      dependent.

PMID- 14580613
TI  - A study of the dynamic interactions between sleep EEG and heart rate variability
      in healthy young men.
AB  - OBJECTIVE: We investigated the interactions between heart rate variability and
      sleep electroencephalogram power spectra. METHODS: Heart rate and sleep
      electroencephalogram signals were recorded in 8 healthy young men. Spectral
      analysis was applied to electrocardiogram and electroencephalogram recordings.
      Spectral components of RR intervals were studied across sleep stages. The cross
      spectrum maximum was determined as well as coherencies, gains and phase shifts
      between normalized high frequency of RR intervals and all electroencephalographic
      frequency bands, calculated over the first 3 NREM-REM cycles. RESULTS: RR
      intervals increased from awake to NREM and decreased during REM. Normalized low
      frequency decreased from awake to NREM and increased during REM while normalized
      high frequency evolved conversely. Low to high frequency ratio developed in
      opposition to RR intervals. Coherencies between normalized high frequency and
      power spectra were high for all bands. The gain was highest for delta band. Phase
      shift between normalized high frequency and delta differed from zero and
      modifications in normalized high frequency preceded changes in delta by 41+/-14
      degrees. CONCLUSIONS: Our study demonstrates that: (1) all
      electroencephalographic power bands are linked to normalized high frequency; (2)
      modifications in cardiac vagal activity show predominantly parallel changes and
      precede changes in delta band by a phase shift corresponding to a lead of 12+/-5
      min.

PMID- 14580614
TI  - Seizure detection: correlation of human experts.
AB  - OBJECTIVE: The description and application of a new, overlap-integral comparison
      method and the quantification of human vs. human accuracies that can be used as
      goals for algorithms. METHODS: Four human experts marked ten 8 h
      electroencephalography (EEG) records from seizure patients. The seizures varied
      in origin and type, including complex partial, generalized absence, secondarily
      generalized and primary generalized tonic-clonic. The traditional any-overlap
      comparison method is used in addition to the overlap-integral method, which is
      sensitive to the correct placement of the seizure endpoints. RESULTS: The number
      of events marked by each reader ranged from 57 to 77. The average any-overlap
      sensitivity and false positives per hour rate are 0.92 and 0.117. The average
      overlap-integral correlation, sensitivity and specificity are 0.80, 0.82 and
      0.9926. As expected, the correspondence between readers is high, but confounding
      issues resulted in overlap-integral sensitivities less than 0.5 for 10% of the
      records. Seven percent of the any-overlap sensitivities are less than 0.5. A
      comparison of the methods by record shows that the overlap-integral specificity
      and the any-overlap false positive rate measure different features. CONCLUSIONS:
      There was little variation between readers and they were essentially
      interchangeable. High seizure rate (many per hour), short seizure durations (<10
      s) and long seizure durations (approximately 10 min) with ambiguous offsets can
      complicate the analysis and result in poor correlation. There may be any number
      of unmarked events in rigorously marked records and it may be preferable to use
      records from non-epilepsy patients to compute the false positive rate. The any
      overlap and overlap-integral comparison methods are complementary. SIGNIFICANCE:
      Correlation between expert human readers can be low on some records, which will
      complicate testing of seizure detection algorithms.

PMID- 14580615
TI  - Callosal role in generation of epileptiform discharges: quantitative analysis of
      EEGs recorded in patients undergoing corpus callosotomy.
AB  - OBJECTIVE: Corpus callosotomy tends to decrease seizure frequency and severity
      rather than transforming the seizure pattern from a generalized form into a
      lateralized or a partial one. The finding implies that bisection of the corpus
      callosum (CC) disrupts the epileptogenicity itself. In order to gain further
      insight into the possible role played by the CC in intractable generalized
      epilepsy, quantitative analyses of long-term EEGs were performed. METHODS:
      Analyses were made of epileptiform discharges contained in the pre- and
      postoperative long-term EEGs in 7 patients who had an anterior callosotomy for
      intractable epilepsy. The duration, number, and amplitude of all epileptiform
      burst activities were measured and statistically analyzed. RESULTS: After
      callosotomy, the total number of epileptiform burst activities, mean duration,
      and the total number of spike discharges decreased significantly. The two
      hemispheres could be divided into dominant and non-dominant ones as to the
      quantity of the residual epileptiform discharges. CONCLUSIONS: Corpus callosotomy
      unevenly reduced preoperative epileptiform discharges in both hemispheres,
      suggesting a facilitatory role played by the callosal neurons that enables the
      asymmetrical epileptogenic susceptible state of the two hemispheres to develop
      bisynchronous and bisymmetrical epileptiform discharges. SIGNIFICANCE: Corpus
      callosotomy decreased the quantity of the epileptiform discharges, suggesting the
      transhemispheric facilitation of seizure mechanisms.

PMID- 14580616
TI  - Sudomotor nerve conduction velocity and central processing time of the skin
      conductance response.
AB  - OBJECTIVE: To estimate the sudomotor nerve conduction velocity (CV), the central
      processing time (CPT) and habituation of the skin conductance response (SCR).
      METHODS: SCRs in response to a single deep inspiratory breath, an electrical
      stimulus and a sound click were obtained from the fingers and toes of 30 healthy
      adults. Sudomotor nerve conduction velocities were determined after measuring
      extremity length and latency differences. CPT was estimated by subtracting the
      efferent time and the known afferent times and neuroeffector times from the onset
      latency. RESULTS: The inspiratory SCR habituated slower than the auditory or
      electrical SCRs. CVs of the 3 modalities did not differ statistically and their
      mean was 1.07 m s(-1) (95% CI: 1.01-1.13). The inspiratory SCR arrived at the
      fingers 1.26+/-0.09 s after the onset of chest wall movement. Electrical and
      auditory SCR onset latencies at the fingers were 1.60+/-0.03 and 1.75+/-0.04 s,
      respectively. Their CPTs were 140 and 160 ms, estimated from the electrical and
      auditory SCR onset latencies to the fingers. The CPT for inspiratory SCR was
      estimated to occur during the inspiratory CPT after the inspiratory decision and
      before chest movement. CONCLUSIONS: In contrast to the SCR following an
      electrical or auditory stimulus, initiation of deep inspiratory SCR occurs before
      the inspiratory act, precluding any possible input from respiratory afferent
      receptors and implicating a central generator. SIGNIFICANCE: This study provides
      new insights into the origin of the SCR following inspiration.

PMID- 14580617
TI  - Impairment of transcallosal inhibition in patients with corticobasal
      degeneration.
AB  - OBJECTIVE: To evaluate the motor function of the transcallosal pathways in
      patients with clinical diagnosis of corticobasal degeneration (CBD). METHODS: In
      a group of 7 patients (4 males, 3 females; mean age 70.6 years) with clinical
      diagnosis of probable CBD (and in 8 age-matched normal controls) we evaluated the
      suppression of the ongoing voluntary EMG activity in the opponens pollicis muscle
      induced by focal transcranial magnetic stimulation (TMS) of the ipsilateral hand
      motor cortex. Such ipsilateral silent period (iSP) is mediated from one motor
      cortex to the contralateral side via a transcallosal pathway. In addition, CBD
      patients were investigated with magnetic resonance imaging (MRI) and
      neuropsychological assessment. RESULTS: iSP was normal in 4 CBD patients, while
      it was bilaterally disrupted in the other 3. MRI showed an atrophy of the corpus
      callosum (middle-posterior part of the trunk) in the CBD patients with iSP
      disruption. Neuropsychological evaluation showed in patients with iSP impairment
      a decrease of verbal fluencies associated with an impairment of attentive
      function. CONCLUSIONS: A proportion of CBD patients shows physiological evidence
      of impaired callosal motor function and atrophy of the corpus callosum on MRI,
      possibly correlated to dysphasic and cognitive disorders.

PMID- 14580618
TI  - Age and gender effects on heart rate activation associated with periodic leg
      movements in patients with restless legs syndrome.
AB  - OBJECTIVE: Periodic leg movements during sleep (PLMS) are often associated with
      electroencephalographic (EEG) changes, such as microarousals (MA), and with heart
      rate (HR) variations. The aim of the present study was to evaluate the effects of
      age and gender on HR changes associated with PLMS in restless legs syndrome (RLS)
      patients. METHODS: Forty-two RLS patients underwent one night of polysomnographic
      recordings. They were divided into 3 groups of 14 subjects (7 women and 7 men)
      according to age, i.e. young (25-40 years), middle-aged (41-55 years) and elderly
      (56-71 years) patients. The RR interval was calculated for 5 intervals before and
      15 intervals after the onset of 50 PLMS in each patient. RESULTS: PLMS were
      associated with HR changes characterized by a tachycardia followed by a
      bradycardia. However, a reduction in the tachycardia and the bradycardia was
      observed with age. Moreover, women showed a higher amplitude in the bradycardia
      than men. No age or gender difference was found for MA index and duration.
      CONCLUSIONS: This study showed age and gender differences in the magnitude of the
      HR changes associated with PLMS. The knowledge of HR variations during sleep,
      including rapid HR changes associated with sleep events such as PLMS or MA, may
      be helpful in understanding the potential mechanisms involved in the increased
      cardiac risk observed in elderly.

PMID- 14580619
TI  - Central motor conduction differs between acute relapsing-remitting and chronic
      progressive multiple sclerosis.
AB  - OBJECTIVE: To characterize central motor conduction in relation to the clinical
      deficits and to the disease duration in 90 patients with acute relapsing
      remitting MS (RR-MS) and in 51 patients with chronic primary or secondary
      progressive MS (P-MS). METHODS: The triple stimulation technique (TST) was used
      to quantify the central motor conduction failure (expressed by the TST amplitude
      ratio) and conventional motor evoked potentials (MEPs) were used to measure the
      central motor conduction time (CMCT). RESULTS: The TST amplitude ratio was
      reduced in presence of a clinical motor deficit (p=0.02 for RR-MS, p<0.01 for P
      MS), but did not significantly differ in RR-MS and P-MS (p>0.05) when patients
      with similar clinical motor deficit were compared. The CMCT was not related to
      the clinical motor deficit in both RR-MS and P-MS. However, the CMCT was markedly
      prolonged in P-MS, when patients with similar clinical motor deficit and with
      similar disease duration were compared (p<0.01). The differences were not
      attributable to differential involvement of the spinal cord, which was similar in
      RR-MS and P-MS. CONCLUSIONS: Our results disclose differences between the central
      motor conduction in RR-MS and P-MS that are not related to disease severity,
      spinal cord involvement or disease duration.

PMID- 14580620
TI  - Modeling the effects of electrical conductivity of the head on the induced
      electric field in the brain during magnetic stimulation.
AB  - OBJECTIVE: The objective of this document is to quantify the effect of changing
      conductivity within the brain in transcranial magnetic stimulation. METHODS:
      Extreme examples of white and grey matter distributions as well as cerebral
      spinal fluid are analyzed with numerical boundary element methods to show that
      the induced E fields for these various distributions vary little from the
      homogeneous case. RESULTS: Models representative of the brain that demarcate
      regions of white matter and grey matter add an unnecessary level of complexity to
      the design and analysis of magnetic stimulators. The induced E field varies
      little between a precise model with exact placement of white and grey matter from
      that of its homogeneous counterpart. The E field will increase in white matter,
      and decrease in grey, but the variation is small. The contour integral of the E
      field around a closed path is dictated by the flux change through that contour.
      DISCUSSION: The maximum value of the variation of the electric field between a
      fully homogeneous medium, and one filled with different conductivity media is 1/2
      the conductivity ratio of the media involved. Neuronal stimulation is more likely
      at the interface between dissimilar mediums, the greatest being between white
      matter and cerebral spinal fluid. The interface location where no normal electric
      field exists will witness a localized electric field 51% greater than the
      homogeneous E field on the white matter side of that interface. White-grey matter
      interfaces will have a maximum localized increase in the E field 22.9% greater
      than the homogeneous case. CONCLUSIONS: Variations in neural intracellular
      potential during a magnetic stimulation pulse will be small among patients. The
      most efficient modeling will follow by assuming the medium homogeneous, and
      noting that perturbations from this result will exist.

PMID- 14580621
TI  - A TMS coil positioning/holding system for MR image-guided TMS interleaved with
      fMRI.
AB  - OBJECTIVE: Transcranial magnetic stimulation (TMS) can be interleaved with fMRI
      to visualize regional brain activity in response to direct, non-invasive,
      cortical stimulation, making it a promising tool for studying brain function. A
      major practical difficulty is accurately positioning the TMS coil within the MRI
      scanner for stimulating a particular area of brain cortex. The objective of this
      work was to design and build a self-contained hardware/software system for MR
      guided TMS coil positioning in interleaved TMS/fMRI studies. METHODS: A compact,
      manually operated, articulated TMS coil positioner/holder with 6 calibrated
      degrees of freedom was developed for use inside a cylindrical RF head coil, along
      with a software package for transforming between MR image coordinates, MR scanner
      space coordinates, and positioner/holder settings. RESULTS: Phantom calibration
      studies gave an accuracy for positioning within setups of dx=+/-1.9 mm, dy=+/-1.4
      mm, dz=+/-0.8 mm and a precision for multiple setups of dx=+/-0.8 mm, dy=+/-0.1
      mm, dz=+/-0.1 mm. CONCLUSIONS: This self-contained, integrated MR-guided TMS
      system for interleaved TMS/fMRI studies provides fast, accurate location of motor
      cortex stimulation sites traditionally located functionally, and a means of
      consistent, anatomy-based TMS coil positioning for stimulation of brain areas
      without overt response.

PMID- 14580622
TI  - Safety criteria for transcranial direct current stimulation (tDCS) in humans.

PMID- 14580626
TI  - Commuting to school: are children who walk more physically active?
AB  - BACKGROUND: The journey to school is an opportunity for increasing children's
      daily physical activity. However, the contribution that active commuting to
      school makes to overall physical activity is unknown. This study used objective
      measurement to investigate the physical activity patterns of children by mode of
      travel to school. METHODS: Primary-school children wore an accelerometer
      programmed to record minute-by-minute physical activity for 7 days and completed
      a brief questionnaire describing their usual travel to school. The total volume
      of physical activity and the time spent in activity of at least moderate
      intensity, as recorded by the accelerometer, was estimated for weekdays and the
      weekend, and groups of children were compared by mode of transport to school.
      Data were collected in May/June 2002. RESULTS: Of the 114 children (59 boys, 55
      girls; aged 10.4+/-0.8 years) who took part in the study, those who walked to
      school (65%) were significantly more active than those who traveled by car
      (712.0+/-206.7 vs 629.9+/-207.2 accelerometer counts per minute, p=0.05).
      Analysis by gender indicated that the major differences in physical activity
      between travel groups were seen only in boys. Hourly activity patterns
      demonstrated that boys who walked to school were more active after school and
      throughout the evening than were car users. CONCLUSIONS: In boys, walking to
      school was associated with higher physical activity after school and during the
      evening. Active transport may contribute to a more physically active profile, at
      least for boys, supporting walk-to-school initiatives to increase children's
      physical activity.

PMID- 14580627
TI  - Evaluating a model of parental influence on youth physical activity.
AB  - OBJECTIVE: To test a conceptual model linking parental physical activity
      orientations, parental support for physical activity, and children's self
      efficacy perceptions with physical activity participation. PARTICIPANTS AND
      SETTING: The sample consisted of 380 students in grades 7 through 12 (mean age,
      14.0+/-1.6 years) and their parents. Data collection took place during the fall
      of 1996. MAIN OUTCOME MEASURES: Parents completed a questionnaire assessing their
      physical activity habits, enjoyment of physical activity, beliefs regarding the
      importance of physical activity, and supportive behaviors for their child's
      physical activity. Students completed a 46-item inventory assessing physical
      activity during the previous 7 days and a 5-item physical activity self-efficacy
      scale. The model was tested via observed variable path analysis using structural
      equation modeling techniques (AMOS 4.0). RESULTS: An initial model, in which
      parent physical activity orientations predicted child physical activity via
      parental support and child self-efficacy, did not provide an acceptable fit to
      the data. Inclusion of a direct path from parental support to child physical
      activity and deletion of a nonsignificant path from parental physical activity to
      child physical activity significantly improved model fit. Standardized path
      coefficients for the revised model ranged from 0.17 to 0.24, and all were
      significant at the p<0.0001 level. CONCLUSIONS: Parental support was an important
      correlate of youth physical activity, acting directly or indirectly through its
      influence on self-efficacy. Physical activity interventions targeted at youth
      should include and evaluate the efficacy of individual-level and community-level
      strategies to increase parents' capacity to provide instrumental and motivational
      support for their children's physical activity.

PMID- 14580628
TI  - Exercise, body mass index, caloric intake, and cardiovascular mortality.
AB  - BACKGROUND: The association of physical inactivity and elevated body mass index
      (BMI) with cardiovascular disease (CVD) risk is well established. The
      relationship of dietary caloric intake and CVD risk is less certain. METHODS: The
      epidemiologic follow-up of the First National Health and Nutrition Examination
      Survey (1971-1992) was examined to determine the relationship of caloric intake,
      BMI, and physical activity to CVD mortality. Of 14,407 participants, 9790
      subjects aged 25 to 74 years met inclusion criteria. The CVD mortality rate was
      the outcome. RESULTS: During the 17 years of follow-up, there were 3183 deaths,
      1531 of which were due to CVD (9.11/1000 person-years). People with relatively
      less physical activity, lower caloric intake, and who were overweight (BMI 25 to
      29.9 kg/m(2)) and obese (BMI > or =30 kg/m(2)) had a less favorable baseline CVD
      risk profile than did those who were more active and of normal weight and had
      greater caloric intake. Age- and race/ethnicity-adjusted CVD mortality rates were
      highest among those with the least physical activity and lowest caloric intake,
      and who were overweight or obese. Moreover, subjects of normal weight who
      exercised most were more likely to have high caloric intake and lower CVD
      mortality (5.9 vs 14.7 per 1000 person-years, p =0.01) than subjects who were
      obese and exercised least. In Cox regression analysis, controlling for relevant
      CVD risk factors, least physical activity was independently associated with
      increased CVD mortality (hazard ratio=1.32, 95% confidence interval [CI]=1.13
      1.53); and obesity was associated with increased CVD mortality (hazard
      ratio=1.24, 95% CI=1.06-1.44). Although highest dietary caloric intake was
      associated with reduced CVD mortality (hazard ratio=0.83, 95% CI=0.74-0.93),
      after adjusting for physical activity and BMI, there was no significant
      association of highest caloric intake with CVD mortality (hazard ratio=0.91, 95%
      CI=0.81-1.01). CONCLUSIONS: In this large general population sample, lower levels
      of physical activity and obesity were independently associated with decreased CVD
      survival. Moreover, when BMI, physical activity, and other relevant
      characteristics were taken into account, caloric intake was not related to CVD
      mortality.

PMID- 14580629
TI  - Relationships between body mass indices and surgical replacements of knee and hip
      joints.
AB  - BACKGROUND: Osteoarthritis is both the most common form of arthritis and the most
      common reason for joint replacement surgery. Obese persons are believed to be
      more likely to develop generalized osteoarthritis that leads not only to knee but
      also to hip joint replacement surgeries. We hypothesized that obesity is also a
      risk for partial joint replacements and surgical revisions. METHODS: A frequency
      matched case-control study was conducted in Utah. Between 1992 and 2000, 840 hip
      and 911 knee joint replacement surgery patients, aged 55 to 74 years, were
      included in this study. Cases were randomly matched to 5578 controls, defined as
      Utah residents enrolled in a cancer screening trial. Odds ratios (ORs) were
      calculated using ICD-9 (International Classification of Diseases, 9th revision)
      procedural codes and body mass index (BMI) groups. RESULTS: There was a strong
      association between increasing BMI and both total hip and knee replacement
      procedures. In males, the highest OR was for those weighing 37.50 to 39.99
      kg/m(2) (total hip: OR=9.37, 95% confidence interval [CI] 2.64-33.31; total knee:
      OR=16.40; 95% CI 5, 19-51.86). In females, the highest OR was for those weighing
      > or =40 kg/m(2) (total hip: OR=4.47; 95% CI, 2.13-9.37; total knee: OR=19.05;
      95% CI, 9.79-37.08). There were slight gender-specific differences in risk found
      for partial hip replacement procedures. Unexpectedly, no statistically
      significant association was found between obesity and the risk for hip or knee
      revision procedures. CONCLUSIONS: While there is an association between obesity
      and hip and knee joint replacement surgeries, obesity does not appear to confer
      an independent risk for hip or knee revision procedures.

PMID- 14580630
TI  - Sustainability of a practice-individualized preventive service delivery
      intervention.
AB  - BACKGROUND: The long-term effect of most interventions has not been studied.
      Changes due to interventions to improve patient care may revert to baseline after
      the intervention stimulus ends. This analysis reports the 24-month follow-up of a
      practice-tailored intervention to increase preventive service delivery rates.
      DESIGN: Group randomized clinical trial with 24-month follow-up of intervention
      sites. SETTING/PARTICIPANTS: Seventy-seven community family practices in
      northeast Ohio. INTERVENTION: Practice-individualized facilitation of
      implementation of tools and approaches. MAIN OUTCOME MEASURES: Summary scores of
      health habit counseling, screening, and immunization services recommended by the
      U.S. Preventive Services Task Force that were up to date for consecutive patients
      during randomly selected chart review days. RESULTS: Previously reported
      increases in global preventive service delivery rates, health habit counseling,
      and screening rates at 12 months were sustained after 24 months. CONCLUSIONS: A
      practice-individualized approach can result in sustainable increases in rates of
      preventive service delivery, even 1 year after the outside intervention stimulus
      ends. Tailoring of approaches to the unique characteristics of each practice may
      result in institutionalization of changes.

PMID- 14580631
TI  - Preventive care: female cancer screening, 1996-2000.
AB  - BACKGROUND: Low-income and uninsured women have lower odds of receiving age
      appropriate cancer screens that can detect cancers earlier and reduce
      morbidity/mortality. A key question is whether federal/state public health
      programs aimed at increasing screening and other public policies (e.g., welfare
      reform, managed care) have affected their receipt of these preventive services.
      METHODS: Data from the Behavioral Risk Factor Surveillance System (BRFSS) were
      used to estimate the effects of public programs, income, and insurance status on
      the odds that women received mammography, clinical breast examination (CBE), or
      Papanicolaou (Pap) smears from 1996 to 2000. State fixed-effects models are
      estimated. Effects of the age (measured in years) of states' National Breast and
      Cervical Cancer Early Detection Programs (NBCCEDPs) and level of federal funding
      are presented. RESULTS: Adjusted odds of uninsured women reporting female cancer
      screens were lower than for those privately insured, and did not change between
      1996 and 2000 despite welfare reform and increasing numbers of uninsured. The age
      of states' NBCCEDPs were associated with increased odds of mammography, CBE, and
      Pap smear screens for non-elderly women. For example, the aging of a state's
      program from 0 to 5 years was associated with an increase in the percentage of
      women receiving mammography from 52.7% to 55.1%. CONCLUSIONS: Despite efforts to
      increase screening among low-income uninsured women, their average rates remain
      below those with higher incomes and/or insurance. However, initiation and
      maintenance of the states' NBCCEDPs over long periods is associated with
      increased screening. After accounting for program age, increased federal dollars
      are associated with slight increases in screening for women aged >65.

PMID- 14580632
TI  - Reminder letter, tailored stepped-care, and self-choice comparison for repeat
      mammography.
AB  - BACKGROUND: The main benefits of mammography come from regular on-schedule
      screening. However, few studies have examined interventions to achieve repeat
      screening. SETTING AND PARTICIPANTS: Participants were women aged 50 to 74,
      recruited through one setting in Rhode Island and another in North Carolina.
      Participants had a mammogram already scheduled at recruitment, and had to keep
      that appointment in order to be eligible for the repeat mammography intervention.
      A total of 1614 women were in the intervention sample. DESIGN: A four-group
      randomized design was used: Group 1, a simple reminder letter; Group 2, a 2
      month, tailored, stepped intervention delivered 2 months after the completed
      mammogram; Group 3, a 10-month, tailored, stepped intervention delivered 2 months
      before the repeat mammogram was due; and Group 4, self-choice of one of the above
      three strategies. INTERVENTION: The intervention took place between June 1996 and
      May 1997. The reminder letter and two levels of the stepped intervention were
      delivered by mail. The third level of the stepped strategy was a counselor
      telephone call. Groups 2 and 3 were identical, except for timing. OUTCOME
      MEASURE: Obtaining the next due mammogram within 15 months, based on clinic
      records. RESULTS: There were no statistically significant differences among the
      four groups, both in the total sample and at the two sites separately.
      CONCLUSIONS: On average, a simple reminder may be as effective as more complex
      strategies for women with a prior on-schedule exam. However, attention is still
      needed to identify women at risk of lapsing from screening. Some women may
      require more-intensive interventions.

PMID- 14580633
TI  - Low public recognition of major stroke symptoms.
AB  - BACKGROUND: A Healthy People 2010 objective includes increasing public awareness
      of the warning signs of stroke, yet few data exist about the level of awareness.
      Recognition of stroke symptoms and awareness of the need to call 911 for acute
      stroke events were examined among the general population. METHODS: Data are from
      61,019 adults participating in the 2001 Behavioral Risk Factor Surveillance
      System, a state-based telephone survey. Respondents indicated whether the
      following were symptoms of stroke: confusion/trouble speaking; numbness/weakness
      of face, arm, or leg; trouble seeing; chest pain (false symptom); trouble
      walking, dizziness, or loss of balance; and severe headache with no known cause.
      Persons also reported the first action they would take if they thought someone
      was having a stroke. RESULTS: Only 17.2% of respondents overall (5.9% to 21.7% by
      state) correctly classified all stroke symptoms and indicated that they would
      call 911 if they thought someone was having a stroke. Recognition of all symptoms
      and knowledge of when to call 911 were comparable by gender but lower among
      ethnic minorities, younger and older people, those with less education, and
      current smokers compared to whites, middle-aged people, those with more
      education, and nonsmokers, respectively. There were no substantive differences by
      history of hypertension, diabetes, heart disease, or stroke. CONCLUSIONS: Public
      recognition of major stroke symptoms is low. Educational campaigns to increase
      awareness among the general population and targeted messages to those at high
      risk persons and their families may help to improve time to treatment for adults
      suffering acute strokes.

PMID- 14580634
TI  - State firearm laws and rates of suicide in men and women.
AB  - BACKGROUND: To evaluate the associations of state laws restricting firearms and
      incidence rates of suicide in men and women using a cross-sectional design.
      METHODS: States were divided into three categories based on the restrictiveness
      of their firearm laws: restrictive (n =8); modest (n =22); and unrestrictive (n
      =20). State suicide incidence rates stratified by gender were compared using
      Poisson regression analyses that controlled for measures of race/ethnicity,
      income, and urbanization. Analyses were based on 2000 census data and state
      suicide data from 1999 and 2000. RESULTS: In the analysis of women, compared to
      states with restrictive firearm laws, there were higher suicide incidence rate
      ratios (IRR) in states with modest (IRR=1.64; 95% confidence interval [CI], 1.34
      2.01) and unrestrictive laws (IRR=1.55; 95% CI, 1.23-1.95). The analysis of men
      showed comparable results: modest firearm laws (IRR=1.51; 95% CI, 1.27-1.79);
      unrestrictive firearm laws (IRR=1.49; 95% CI, 1.23-1.82). CONCLUSIONS: Results
      support the hypothesis that state restrictions on firearms have the potential to
      reduce the suicide rate. Findings do not support a hypothesis that greater
      firearm restrictions are associated with the substitution of alternative methods
      of suicide. Firearms appear to be a comparable exposure for suicide in men and
      women. Although men are more likely to use firearms in suicide than women, this
      difference may merely reflect more frequent gun ownership among men.

PMID- 14580636
TI  - SCOPE: SCripture Oriented Preventive Education.
AB  - BACKGROUND: Counseling to effect lasting change in health behaviors has proven
      only moderately effective. The Torah, or Five Books of Moses, conveys many of the
      key messages regularly promulgated by prevention professionals. The promise of
      synergy with the behavioral messages of preventive medicine among devout
      Scripture-based adherents led to the development of a SCripture Oriented
      Preventive Education (SCOPE) tool. METHODS: Forty-eight SCOPE articles were
      written to complement the weekly Torah portion read throughout the year in
      Orthodox Jewish synagogues. These were disseminated via newsletter within a
      modern Orthodox Jewish community in Israel. Two articles are included. An age
      stratified, 25% random sample (120/471) of community readership was surveyed to
      ascertain receptivity to SCOPE and to gauge support for future implementation.
      RESULTS: Response rate was 76% (92/120). Lifestyle behavior-related articles were
      most popular (77% found them interesting) and injury prevention the least (41%).
      Knowledge gained was the most common benefit reported (55% of respondents),
      followed by attitude change (24%). Those aged 30 to 49 years were significantly
      more likely than others to report behavior change (p=0.002) and health
      improvement (p=0.005) secondary to SCOPE. Clinical prevention (p=0.007) and
      environmental health (p=0.03) articles were significantly more popular in people
      aged > or =30 and 30 to 49, respectively. Between 69% and 84% supported the
      implementation of SCOPE in secondary schools, by physicians, and/or rabbis.
      CONCLUSIONS: SCOPE was designed to deliver prevention materials to faith
      communities via a Scripture-based vehicle. A postexposure readership survey in an
      Israeli Orthodox Jewish community demonstrated its effectiveness. SCOPE's
      ultimate utility as a counseling adjunct in Scripture-adherent communities awaits
      broader assessment.

PMID- 14580635
TI  - Risks for abuse against pregnant Hispanic women: Morelos, Mexico and Los Angeles
      County, California.
AB  - BACKGROUND: Although violence against women is gaining international attention as
      a prevention priority, little is known about how risks differ across countries.
      METHODS: A comparative study of violence against pregnant Mexican women in
      Morelos, Mexico, and Latina women in Los Angeles County, California, United
      States. In 1998 and 1999, women in prenatal clinics were interviewed about
      psychological abuse and sexual and physical violence by their partner, during and
      the 1 year prior to the index pregnancy. The overall response rate for Morelos
      was 99%, with a sample size of 914; Los Angeles County had a response rate of
      96.9%, with a sample size of 219. RESULTS: Women in Morelos reported a higher
      prevalence of violence compared to women in the California (14.8% v 11.9%,
      respectively). A partner aged <20 years was associated with increased violence in
      both countries, but the association of violence with other socioeconomic factors
      differed by country. For example, employed women had higher odds of violence in
      California but lower odds in Morelos. Women who experienced violence during both
      the year prior to pregnancy and as a child were more than 25 times more likely to
      be abused during pregnancy than women not reporting this type of abuse.
      CONCLUSION: The identification of factors associated with violence against women,
      especially as they differ by culture and ethnicity, will help clinicians to
      better identify victims and to design and implement culturally appropriate
      prevention programs.

PMID- 14580637
TI  - Patients' achievement of cholesterol targets: a cross-sectional evaluation.
AB  - BACKGROUND: Despite incontrovertible evidence for the efficacy of cholesterol
      lowering, numerous studies suggest that patients are suboptimally treated. This
      study was conducted to determine the proportion of patients achieving recommended
      target lipid levels in a relatively unselected group of community-dwelling
      patients who were prescribed HMG-CoA reductase inhibitors (statins). METHODS:
      Community pharmacists identified participants who were receiving an HMG-CoA
      reductase inhibitor at the same dosage for a minimum of 6 weeks and enrolled them
      into the study. Participants had an interview to determine cardiovascular risk
      factors and level of cardiovascular risk as defined by Canadian dyslipidemia
      guidelines, and a fasting lipid profile was performed using a point-of-care
      cholesterol assessment device. RESULTS: During 2000, a total of 404 participants
      were enrolled from 16 pharmacies. The highest proportion (96%) of participants
      achieving low-density lipoprotein targets was in the low-risk group, and the
      proportion progressively decreased as cardiac risk level increased: 80% in the
      moderate-risk group and 82% in the high-risk group. The very-high-risk group had
      the lowest proportion (37%) of participants who achieved their target.
      CONCLUSIONS: Consistent with other studies, this study found that as cardiac risk
      increased, the proportion of patients achieving their target cholesterol values
      decreased, such that those at the greatest risk for cardiovascular disease (who
      had the most to gain from aggressive lipid-lowering interventions) were least
      likely to achieve their cholesterol targets. This suggests a need for more
      aggressive approaches to the management of cholesterol, particularly in high-risk
      patients.

PMID- 14580639
TI  - Developing quality indicators for local health departments: experience in Los
      Angeles County.
AB  - OBJECTIVES: To develop public health quality indicators for local health
      department (LHD) use. METHODS: An indicator development team utilized public
      health quality measurement concepts, reviewed existing quality measurement
      related initiatives, and conducted interviews with LHD staff in order to identify
      and develop quality indicators for the Los Angeles County Health Department.
      RESULTS: Sixty-one recommended and 50 acceptable (i.e., scientifically sound but
      less useful) indicators were developed, with an emphasis on measuring process
      quality in services delivery. Pre-existing indicators from external sources, when
      available, were often not well suited to the Health Department's needs. The
      indicator development process clarified conceptual issues, highlighted strengths
      and limitations of potential indicators, and revealed implementation barriers.
      CONCLUSIONS: A limited number of generally available, quantitative indicators of
      local public health quality exist. Indicators addressing the delivery of LHD
      services can be locally developed to fill an important gap in public health
      quality-improvement efforts. However, implementation of quality measurement is
      difficult due to limited evidence on public health practices, sparse data
      resources, unclear accountability, and inconsistent organizational motivation.

PMID- 14580638
TI  - Costs of a hepatitis A outbreak affecting homosexual men: Franklin County, Ohio,
      1999.
AB  - BACKGROUND: Hepatitis A is one of the most commonly reported, vaccine-preventable
      diseases in the United States. Many cases occur in association with community
      wide outbreaks, but societal costs to the community are seldom documented.
      METHODS: Hepatitis A case-patients available for a follow-up interview as part of
      an outbreak investigation were asked about hospitalization, healthcare costs,
      missed work, and lost wages associated with their illness, as well as healthcare
      insurance coverage and sick-leave reimbursement. Average costs were calculated by
      case-patient age, gender, and hospitalization status for lost wages, and by age
      and hospitalization status for medical costs, and then assigned to case-patients
      not re-interviewed to provide an estimate of overall costs. Health departments
      provided outbreak-associated costs. RESULTS: Between the weeks of November 2,
      1998, and May 17, 1999, a total of 136 cases of hepatitis A were reported. Of the
      89 (65.4%) case-patients available for interview, 74 (83%) were male; of those,
      47 (64%) identified themselves as men who have sex with men (MSM). The average
      cost of the outbreak per case-patient was $2894 US dollars, of which 51% was
      associated with lost wages, 40% with medical costs, and 9% with health department
      costs. Case-patients incurred 44% of total outbreak costs; employers, 29%;
      healthcare insurers, 18%; and health departments, 9%. CONCLUSIONS: In this
      community-wide hepatitis A outbreak, case-patients incurred the largest portion
      of costs, followed by employers, healthcare insurers, and health departments.

PMID- 14580640
TI  - Pediatric smoking prevention interventions delivered by care providers: a
      systematic review.
AB  - OBJECTIVE: To conduct a systematic review of randomized controlled trials of
      smoking prevention interventions for youth delivered via medical or dental
      providers' offices. METHODS: Online bibliographic databases were searched as of
      July 2002, and reference lists from review articles and the selected articles
      were also reviewed for potential studies. The methodology and findings of all
      retrieved articles were critically evaluated. Data were extracted from each
      article regarding study methods, intervention studied, outcomes measured, and
      results. RESULTS: The literature search returned 81 abstracts from MEDLINE and 49
      from Cochrane Clinical Trials Registry (CCTR); of these, four articles met the
      inclusion criteria. Included were two studies conducted in primary care, and one
      each in dental and orthodontic offices. Only one study demonstrated a significant
      effect on smoking initiation; in that study, 5.1% of the intervention group and
      7.8% of the control group reported smoking at 12-month follow-up (odds ratio=
      0.63; 95% confidence interval, 0.44-0.91). None of the studies had follow-up
      times greater than 3 years. CONCLUSIONS: There is very limited available evidence
      demonstrating efficacy of smoking prevention interventions in adolescents
      conducted in providers' offices and no evidence for long-term effectiveness of
      such interventions.

PMID- 14580641
TI  - Smoking cessation interventions for adolescents: a systematic review.
AB  - OBJECTIVE: To conduct a systematic review of controlled trials for adolescent
      smoking cessation. METHODS: Online bibliographic databases were searched as of
      June 2002, and reference lists from review articles and the selected articles
      were also reviewed for potential studies. The methodology and findings of all
      retrieved articles were critically evaluated. Data were extracted from each
      article regarding study methods, intervention studied, outcomes measured, and
      results. RESULTS: The abstracts or full-text articles of 281 relevant studies
      were examined, of which six met the selection criteria. Included were three
      school-based studies, a study in pregnant adolescent girls, a hospital-based
      study, and a trial of laser acupuncture. All three of the school-based studies
      reported significant impacts on cessation rates, although only one of these was a
      randomized trial. None of the studies had follow-up times of >5.2 months.
      CONCLUSIONS: There is very limited evidence demonstrating efficacy of smoking
      cessation interventions in adolescents, and no evidence on the long-term
      effectiveness of such interventions. Smoking-cessation interventions that have
      proven most effective in adults, such as nicotine replacement and antidepressant
      use, have not been studied in adolescents in a controlled manner.

PMID- 14580642
TI  - Effects of hCG on folliculogenesis and fecundity in mink (Mustela vision Schreb).
AB  - The endogenous hormonal response obtained after reproductive organs are
      challenged by exogenous hormones is increasingly being used to predict presence
      of functional reserves and to apply this information to improve efficiency of
      managed breeding programs. With that in mind, the aim of the present study was to
      investigate the effect of a single treatment with hCG on folliculogenesis and
      fertility in standard 7-month-old mink females. The extent of stimulation
      following treatment was determined by examining patterns of vaginal smears.
      Characteristics of each cycle stage were: estrus, preponderance of cornified
      epithelial cells; proestrus, polygonal, elongate epithelial cells; anestrus,
      parabasal, intermediate and leucocyte cells. Smears exhibiting a mixed population
      of cells were categorized as being in transition between adjacent stages anestrus
      proestrus or proestrus-estrus. The initial evaluations were done on Day 6 after
      hCG treatment. Histomorphometric examination of ovaries and uteri was done during
      seasonal anestrus (November) and in the breeding season (March). Vaginal cytology
      patterns were correlated with changes in folliculogenesis. A mean of 1.3 mature
      (Graafian) follicles were counted during estrus, while the mean number seen
      during anestrus, anestrus-proestrus and proestrus, were 0.4, 0.3 and 1.0,
      respectively. During the breeding season, in females that were not treated, the
      numbers of growing follicles decreased and maturing follicles increased, whereas
      females that came in estrus after treatment with hCG in November had increased
      numbers of both growing and maturing follicles. Fertility after breeding in hCG
      treated females was increased by 9.2% (P<0.05) as compared to untreated females.
      Females showing the highest fertility rise (27%) were predominantly in the group
      that showed estrus after hCG treatment. We conclude that monitoring the response
      of the mink reproductive system to hCG stimulation in November may be a useful
      tool for identifying females of high fertility in the spring.

PMID- 14580643
TI  - Apoptosis in the canine endometrium during the estrous cycle.
AB  - Apoptotic cell death in the endometria of 58 female dogs in different stages of
      the estrous cycle was assessed (in formalin-fixed, paraffin-embedded sections)
      with both the terminal deoxynucleotidyl transferase mediated deoxyuridine
      triphosphate nick end labeling (TUNEL) assay and immunohistochemical detection of
      caspase-3 activity. For both techniques, the apoptotic index was determined in
      the surface epithelium, stroma, crypts, and basal glands by counting the
      percentage of stained cells in a total of 500 cells in each category. In the
      surface epithelium and stroma, TUNEL- and caspase-3-positive cells were rare
      (apoptotic index<1) throughout the estrous cycle. However, caspase-3 detection
      showed a significant increase in the apoptotic index in the stroma during
      anestrus as well as an increase in the index in both the stroma and surface
      epithelium in late metestrus. The apoptotic index increased during late metestrus
      and anestrus in the crypts and basal glands; in the crypts, this increase was
      significant only when caspase-3 detection was used, whereas in basal glands,
      significant differences were found for both techniques. In conclusion, apoptosis
      was present in canine endometrial cells during the estrous cycle, but caspase-3
      detection showed more significant differences than the TUNEL assay. Furthermore,
      a high apoptotic index (suggestive of endometrial desquamation) was not detected
      in the surface epithelium and there was no significant correlation between the
      apoptotic index in any cell group and serum progesterone concentrations.

PMID- 14580644
TI  - Induction and activation of meiosis and subsequent parthenogenetic development of
      growing pig oocytes using calcium ionophore A23187.
AB  - The pig ovary contains a large number of growing oocytes, which do not mature in
      vitro and cannot be readily used in various biotechnologies. This study was
      conducted to determine the possibility of inducing meiotic maturation in growing
      pig oocytes with an internal diameter of 110 microm, which had developed partial
      meiotic competence. Most of these oocytes spontaneously stopped maturation at the
      metaphase I stage (68%); a limited number proceeded to the metaphase II stage
      (26%). Treatment with calcium ionophore A23187 (50 microM for 5 or 10 min) after
      24h in vitro culture overcame the block at the metaphase I stage, and treated
      growing pig oocytes matured to the metaphase II stage (66%). Oocytes in which
      maturation had been induced by calcium ionophore were again treated with calcium
      ionophore. Up to 58% of the treated oocytes were activated. Parthenogenetic
      development in oocytes treated with ionophore for meiosis induction and
      activation was very limited. The portion which reached morula stage did not
      exceed 8% and at most 3% developed to the blastocyst stage.

PMID- 14580645
TI  - Developmental competence and post-thaw survivability of buffalo embryos produced
      in vitro: effect of growth factors in oocyte maturation medium and of embryo
      culture system.
AB  - The present study was conducted to examine the effects of supplementation to IVM
      medium of epidermal growth factor (EGF), fibroblast growth factor (FGF) and
      vasoactive intestinal peptide (VIP) along with pregnant mare serum gonadotrophin
      (PMSG) on oocyte maturation and cleavage of buffalo embryos (experiment 1). The
      developmental competence of cleaved embryos cultured in either a complex co
      culture system (TCM-199+10% serum+oviduct cell monolayer) or defined media (a)
      modified form of synthetic oviductal fluid (mSOF) was evaluated (experiment 2).
      The post-thaw morphology and survivability of frozen blastocysts developed from
      embryos cultured either in complex or defined medium was compared (experiment 3).
      Aspirated oocytes were cultured in maturation medium (TCM-199+PMSG (40 IU/ml
      control)) supplemented with EGF (20 ng/ml), FGF (20 ng/ml) and VIP (20 ng/ml),
      either alone or in combination, in a CO(2) incubator at 38.5 degrees C for 24h.
      Maturation rate was assessed and oocytes were inseminated in vitro with frozen
      thawed sperm processed in Brackett and Oliphant (BO) medium. The cleaved embryos
      were cultured either in complex co-culture system or mSOF. Results suggested that
      EGF had more beneficial effect on buffalo oocyte maturation, and embryo cleavage
      than FGF. Addition of VIP to the oocyte maturation medium did not improve the
      results. Blastocyst yields from buffalo oocytes were significantly higher in a
      complex co-culture system than in defined media (mSOF) when oocytes were matured
      in presence of EGF either alone or in combination with FGF and VIP. The mean
      percent of morphologically normal blastocysts after thawing and their
      survivability were significantly higher in blastocysts obtained from embryos
      cultured in mSOF than those cultured in complex co-culture system.

PMID- 14580646
TI  - The hyaluronic acid receptor (CD44) is expressed in bovine oocytes and early
      stage embryos.
AB  - Hyaluronic acid (HA) is a high molecular weight polysaccharide found in the
      extracellular matrix of most animal tissues, that exerts a profound influence on
      cell behavior. HA is one of the most abundant glycosaminoglycans (GAGs) in the
      uterine, oviductal and follicular fluids in mouse, pig, human and cattle. CD44,
      the principal cell membrane receptor for HA, is expressed from the 1- to 8-cell
      stage in human embryos, during post-implantation mouse embryogenesis and on the
      surface of differentiated embryonic stem cells. In the present study, we have
      analyzed by immunofluorescence, whether CD44 is present in bovine oocytes,
      fertilized oocytes and early stage embryos. Bovine cumulus-oocyte complexes
      (COCs) were aspirated from follicles (2-5mm) and were selected for IVM and
      incubated for 24h. Oocytes showing an expanded cumulus (generally 90-95%) were
      used for IVF. Fertilized oocytes were separated for immunofluorescence assay
      after 16h of sperm incubation in order to fix the eggs at the pronuclear stage.
      The embryos were cultured for 8 days and the different stages of development for
      immunofluorescence assay were separated every 24h of culture. The CD44 receptor
      was detected at every observation time examined. Fluorescence-tagged HA for the
      internalization assay was prepared by mixing fluorescein amine, Isomer I and 1mg
      of HA from umbilical cord. Fluorescence-tagged HA was internalized in 2-, 4-, 8-
      and 16-cell-stage embryos, morulae and blastocysts. CD44 is expressed on the
      surface and in the cytoplasm of bovine oocytes and embryos in different stages of
      development.

PMID- 14580647
TI  - Ovarian follicular wave synchronization and pregnancy rate after fixed-time
      natural mating in llamas.
AB  - The study was designed to compare the efficacy of treatments intended to induce
      follicular wave synchronization among llamas (Experiment 1), and to determine the
      effect of these treatments on pregnancy rates after fixed-time natural mating
      (Experiment 2). In Experiment 1, llamas were treated with: (1) saline (control,
      n=20); (2) estradiol and progesterone (E/P, n=20); (3) LH (LH, n=20); or (4)
      transvaginal ultrasound-guided follicle ablation (FA, n=20). The ovarian response
      was monitored daily by transrectal ultrasonography. The intervals from treatment
      to follicular wave emergence and to the day on which the new dominant follicle
      reached >/=7 mm, respectively, did not differ between the LH (2.1+/-0.3 days and
      5.2+/-0.5 days, respectively) and FA groups (2.3+/-0.3 days and 5.0+/-0.5 days),
      but both were shorter (P<0.05) and less variable (P<0.01) than in the control
      group (5.5+/-1.0 days and 8.4+/-2.0 days), while the E/P group (4.5+/-0.8 days
      and 7.7+/-0.5 days) was intermediate. In Experiment 2, llamas at unknown stages
      of follicular development were assigned randomly to control, E/P, and LH groups
      (n=30 per group). A single, fixed-time natural mating was permitted 10-12 days
      after treatment. Ovulation rates did not differ among groups (control, 93%; E/P,
      90%; LH, 90%; P=0.99), but the pregnancy rate was higher (P<0.05) for
      synchronized llamas (LH and E/P groups combined, 41/54) than for non-synchronized
      llamas (control group, 15/28). In conclusion, LH and FA treatments were most
      effective for inducing follicular wave synchronization, while E/P treatment was
      intermediate. Synchronization treatments did not influence ovulation rate
      subsequent to fixed-time natural mating, but a higher pregnancy rate in
      synchronized than non-synchronized llamas warrants critical evaluation of the
      effects of follicular status on the developmental competence of the contained
      oocyte.

PMID- 14580648
TI  - Development of bovine embryos after in vitro fertilization of oocytes with flow
      cytometrically sorted, stained and unsorted sperm from different bulls.
AB  - The objective of this study was to determine the effect of staining bovine sperm,
      with or without flow cytometry, on in vitro fertilization of bovine oocytes and
      blastocyst development. Bovine oocytes (n=4273) were fertilized with frozen
      thawed sperm from three bulls that was: stained with Hoechst 33342 and sorted
      (into X- or Y-chromosome-bearing sperm) with flow cytometry; stained but not
      sorted; and not stained or sorted (Control). Oocytes, aspirated from
      slaughterhouse ovaries, were matured in TCM199 (supplemented with 10% fetal calf
      serum and 15 ng FSH, 1.0 microg LH, 1.0 microg E2/ml) for 22-24h at 39 degrees C
      in 5% CO(2) in air with maximum humidity. Presumptive zygotes were removed from
      culture and placed in chemically defined medium (CDM-1) 6-7h after insemination
      and cultured for 65-66h. Embryos that had cleaved by 72h post-insemination were
      cultured an additional 96h in CDM-2 containing 0.12 IU insulin/ml. Cleavage and
      blastocyst rates per oocyte inseminated were recorded on Day 3 and Days 7-8 after
      insemination, respectively. There was no significant difference in blastocyst
      rate among the three types of sperm; however, cleavage rates with stained and
      sorted sperm (53.1%) and unsorted, stained sperm (59.9%) were lower (P<0.05) than
      Control sperm (69.7%). Furthermore, there were significant differences due to
      semen from different bulls in cleavage and blastocyst rates.

PMID- 14580649
TI  - The effect of nocturnal sampling on semen quality and the efficiency of
      collection in bovine species.
AB  - This study evaluated night and day semen collection regimes in Holstein and
      Brahman bulls (four bulls of each breed) that were collected weekly, each during
      a morning and a night collection. Ejaculates (n=64) were obtained via artificial
      vagina over 4 weeks. The first collection of each week alternated between night
      and day. Two collection teams were employed. Bull behavior parameters included
      reaction time to first mount, time to ejaculation, a refractory period test, and
      a thrust intensity test. The numbers of interruptions were counted as a
      managerial parameter. Pre-freeze semen parameters included total volume, initial
      motility and concentration. Post-freeze semen parameters measured were: 0- and 3
      h post-thaw motility; percent intact acrosomes; and percent sperm abnormalities.
      Data were analyzed by least squares methods. The bull within breed effect
      differed (P<0.05) for behavior parameters. The bull within breed effect for total
      motile sperm harvested was not significant. The bull within breed response was
      mixed for post-freeze semen viability parameters. Bull within breed was not
      significant for sperm abnormalities. The night versus day treatment was
      significant for the managerial parameter (P=0.002). Although a different
      collection schedule for Bos indicus cattle was not warranted, the efficiency of
      the collection process was affected by extraneous environmental conditions.

PMID- 14580650
TI  - Effects of phosphodiesterase inhibitors on spontaneous nuclear maturation and
      cAMP concentrations in bovine oocytes.
AB  - It was previously demonstrated that inhibition of cAMP degradation with
      phosphodiesterase type 3 (PDE3) inhibitors resulted in the maintenance of bovine
      cumulus-oocyte complexes (COC) and denuded oocytes (DO) in meiotic arrest, while
      a PDE4 inhibitor was without effect. In this study, different inhibitors of PDE3
      and PDE4 were tested for their effects on bovine oocyte nuclear maturation.
      Bovine COC and DO were cultured in TCM-199+10% fetal bovine serum (FBS) with or
      without different concentrations of the PDE inhibitors. The PDE3 inhibitor
      trequinsin significantly increased the percentage of COC remaining at the
      germinal vesicle (GV) stage after 7h of culture (19.3, 60.3, and 67.8% GV for
      control and trequinsin 10 and 50 nM, respectively) while Ro 20-1724 (a PDE4
      inhibitor) was without effect. In DO, only trequinsin at 10 nM had a significant
      effect after 7h of culture (51.3 and 86.1% GV for control and trequinsin 10 nM,
      respectively). Trequinsin reduced the percentage of COC reaching the mature phase
      after 22h, but was without effect on DO. The protein kinase A (PKA) inhibitor H
      89 reversed the inhibitory effect of trequinsin in COC and DO, indicating that
      inhibition of nuclear maturation by trequinsin involves activation of PKA.
      Trequinsin increased cAMP concentrations in COC but not in DO, suggesting that
      cumulus cells may also contain a PDE3 isoenzyme.

PMID- 14580651
TI  - The effect of follicle-stimulating hormone on follicular development, granulosa
      cell apoptosis and steroidogenesis and its mediation by insulin-like growth
      factor-I in the goat ovary.
AB  - The effect of FSH on goat follicular development, granulosa cell apoptosis and
      steroidogenesis and its mediation by insulin-like growth factor (IGF)-I were
      studied through both in vivo and in vitro experiments. The FSH treatment was
      begun on Day 9 after estrus and consisted of injections twice a day for 3 days in
      decreasing doses (7.5-7.5-5.0-5.0-2.5-2.5 mg). Does in both treatment and control
      groups were slaughtered for ovaries on Day 12. Granulosa cell apoptosis was
      detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling
      (TUNEL). Expression of IGF-I and IGF-II mRNA was determined by RT-PCR, while
      concentrations of progesterone (P4), estradiol (E2), IGF-I and IGF-II were
      measured by radioimmunoassay (RIA). Following parameters increased significantly
      (P<0.05) after the FSH treatment: follicle number (5.0+/-1.5 versus 9.0+/-2.0 per
      ovary), the level of E2 (0.1+/-0.1 ng/ml versus 0.7+/-0.2 ng/ml), the E2/P4 ratio
      (0.7+/-0.4 versus 4.7+/-3.0) and the concentrations of IGF-I (0.5+/-0.2 ng/ml
      versus 119.4+/-15.1 ng/ml) and IGF-II (0.12+/-0.03 ng/ml versus 40.9+/-18.7
      ng/ml) in follicular fluid of the medium sized (3-5 mm) follicles and in the
      ovarian cortex the relative quantity of IGF-I mRNA (0.37+/-0.17 versus 0.90+/
      0.12 Max OD). In contrast, the ratio of apoptotic granulosa cells in these
      follicles was reduced significantly (0.53+/-0.1 versus 0.10+/-0.01, P<0.05). In
      large (>5 mm) follicles, however, only the follicle number (2.3+/-0.7 versus
      7.0+/-1.5 per ovary) and the level of IGF-I (38.4+/-11.0 ng/ml versus 87.3+/-13.9
      ng/ml) increased significantly (P<0.05), whereas other values did not change. In
      vitro culture of granulosa cells showed that FSH significantly (P<0.05) enhanced
      IGF-I production (12.7+/-2.1 ng/ml versus 26.+/-21.9 ng/ml) by these cells, and
      both FSH and IGF-I reduced the ratios of apoptotic cells (from 0.7+/-0.07 to
      0.3+/-0.1 and 0.2+/-0.04, respectively) and the effect was additive when both
      were used together. H89, the PKA pathway inhibitor, blocked the effect of FSH on
      granulosa cell apoptosis and IGF-I production in vitro. These results indicated
      that FSH mainly enhanced the development of medium sized follicles in the goat by
      suppressing the apoptosis of granulosa cells via increasing production of IGF-I
      and steroids, possibly through the PKA pathway.

PMID- 14580652
TI  - Serial proton magnetic resonance spectroscopy of the brain in children undergoing
      cardiac surgery.
AB  - We used proton magnetic resonance spectroscopy to study 11 children (age < 8
      years) with congenital heart disease undergoing cardiopulmonary bypass to
      determine whether low (10 +/- 4; n = 6) vs high (20 +/- 4; n = 5) perfusate
      hematocrits during bypass resulted in changes in brain metabolites which
      correlate with neurologic injury. Long and short echo time single voxel magnetic
      resonance spectroscopy in occipital gray matter and neurologic assessment were
      performed preoperatively and 2 and 5 days postoperatively. We also determined
      whether prolonged periods at low flow rates during bypass affected spectroscopy
      variables. We found no significant differences in metabolite ratios between the
      low vs high hematocrit groups or the lower vs higher flow rate groups (repeated
      measures analysis of variance of observation ranks converted to normal scores).
      However, our study was limited by statistical power due to the small sample size,
      therefore no conclusions could be made. Additional studies involving a greater
      number of patients are necessary. In all 11 children, magnetic resonance
      spectroscopy detected a significant decrease in brain N-acetyl-aspartate, and
      increases in myoinositol and glutamate/glutamine after surgery (Quade test)
      demonstrating that magnetic resonance spectroscopy is sensitive in detecting
      subtle postoperative changes in brain metabolites.

PMID- 14580653
TI  - Cognitive performance in a low birth weight cohort at 5 and 11 years of age.
AB  - The objective of this study was to evaluate cognitive functions, changes over
      time, and prenatal, perinatal, and neonatal predictors in low birth weight
      children. A cohort of 130 low birth weight children was compared with 131 control
      children. A neuropsychologic test battery including subtests from the Wechsler
      Intelligence Scale for Children-Revised and the Illinois Test of Psycholinguistic
      Abilities, Knox Cube Test, Grooved Pegboard Test, Finger, and Foot Tapping was
      used. School performance was assessed using the Child Behavior Check List. Low
      birth weight children were comparable with control children in areas of verbal
      and visuo-spatial function, distractibility, and motor tempo, when parental
      factors were controlled for. An apparent association between breast milk feeding
      and child intelligence quotient was rendered insignificant when confounding
      parental factors were controlled for. None of the other identifiable prenatal,
      perinatal, or neonatal predictors were significantly related to cognitive outcome
      or school problems at 11 years of age. No differences were found in cognitive
      functions between those weighing less than 1500 g and 1500-2000 g. Motor problems
      and low verbal intelligence quotient at 5 years of age in the low birth weight
      children (previously published data) each doubled the risk of presenting a school
      problem at 11 years of age. Our findings are encouraging for low birth weight
      children regarding testable cognitive consequences and less encouraging regarding
      ability of cognitive test to identify school problems.

PMID- 14580654
TI  - Neurocognitive outcome after acute disseminated encephalomyelitis.
AB  - Cognitive dysfunction has been demonstrated in multiple sclerosis but has not
      been extensively studied after acute disseminated encephalomyelitis (ADEM).
      Because ADEM often presents with widespread demyelination, which may not
      completely resolve, these patients may be at risk for persistent cognitive
      dysfunction. The study objective was to explore the profile and severity of
      neurocognitive sequelae in pediatric ADEM. Children aged 6-15 years diagnosed
      with ADEM were invited to participate in a structured neurologic assessment,
      neuropsychological evaluation, and a follow-up magnetic resonance imaging. Nine
      of 15 children diagnosed with ADEM met the age criteria and six participated in
      the study. The mean age at presentation was 7.7 years; the mean duration of
      follow-up was 3.5 years. As a group, these children with prior ADEM performed
      within the average range on cognitive testing. However, a variety of mild
      cognitive deficits were demonstrated in each of the children, even in those whose
      magnetic resonance imaging studies had completely normalized. Four children
      demonstrated a cognitive profile of relatively poorer visuospatial/visuomotor
      function. The cognitive deficits observed in these children are similar but less
      severe than those previously reported in adults and children with multiple
      sclerosis, which may reflect the monophasic nature of ADEM, compared with the
      chronic, recurrent demyelination characteristic of multiple sclerosis.

PMID- 14580655
TI  - Sickle cell anemia with moyamoya disease: outcomes after EDAS procedure.
AB  - Moyamoya disease is a relatively uncommon neurovascular complication of sickle
      cell anemia. We report a case series of six patients with sickle cell anemia who
      developed moyamoya disease and underwent encephaloduroarteriosynangiosis
      procedures. These six patients presented with either cerebrovascular accidents,
      transient ischemic attacks, or seizures, and subsequent magnetic resonance
      imaging scans were suggestive of moyamoya-like changes in the cerebral
      vasculature. Conventional cerebral angiography was used to confirm the diagnosis
      in all six patients. Four of six patients manifested a cerebrovascular accident
      before surgery, and two of these patients were compliant on a transfusion
      protocol at the time of their cerebrovascular accident. Bilateral (n = 4) or
      unilateral (n = 2) encephaloduroarteriosynangiosis procedures were performed
      without any complications. The patient who was stroke-free preoperatively had a
      cerebrovascular accident 2 weeks after the procedure; otherwise, all patients
      have remained free of neurovascular complications with an average follow-up of 33
      months. Collateral anastomoses between external and internal carotid arteries
      were established by magnetic resonance angiography in three patients. The
      encephaloduroarteriosynangiosis procedure is a safe and effective treatment
      option in patients with sickle cell anemia who develop moyamoya disease.

PMID- 14580656
TI  - Prevalence and risk of sleep disturbances in adolescents after minor head injury.
AB  - Sleep disturbances were reported in patients during the acute stage after minor
      head injury, and for some of these patients, the disturbances may become chronic.
      The purpose of the present study was to assess the prevalence and risk factors of
      the long-term sleep disturbances in adolescents after minor head injury.
      Unselected adolescents (98) who had experienced a minor head injury 0.5-6 years
      before the institution of the study and 80 matched control subjects were
      interviewed and completed a detailed questionnaire. The prevalence of sleep
      disturbances was significantly larger among adolescents who experienced minor
      head injury compared with the control subjects (28% versus 11%, P < 0.05). Within
      the study group, those who developed long-term sleep disturbances manifested a
      greater body mass index (20.8 +/- 4.0 vs 18.4 +/- 2.8 kg/m(2), P = 0.005) and
      poorer parental education (fathers 11.0 +/- 4.0 vs 13.4 +/- 3.0 years, mothers
      11.8 +/- 3.3 vs 13.2 +/- 2.9 years, P < 0.05 for both), compared with those who
      did not develop sleep disturbances. Our data indicate that subjective sleep
      disturbances may be evident in a fairly high percentage of adolescents after
      minor head injury, up to 28%, suggesting that minor head injury may not be as
      benign as previously estimated. Risk factors include heavier body mass and poorer
      parental education.

PMID- 14580657
TI  - Modafinil in children with attention-deficit hyperactivity disorder.
AB  - Previous clinical evidence suggested that modafinil may improve clinical features
      of children with attention-deficit hyperactivity disorder. To test this
      hypothesis, a randomized, double-blind, placebo-controlled study design was used.
      Of 24 children initially randomized into the study, 11 control subjects and 11
      treatment patients completed the study, with evaluation before medication and
      after 5 to 6 weeks. The average Test of Variables of Attention attention-deficit
      hyperactivity disorder z score improved by 2.53 S.D.s for the modafinil group
      compared with a decline of 1.02 for control patients (P < or = 0.02). Conners
      Rating Scales ADHD total t scores for the modafinil group improved from 76.6 to
      68.2 compared with improvement from 77.7 to 76.0 for control subjects (P = 0.04).
      Ten of 11 treatment patients were reported as "significantly" improved, whereas
      eight of 11 control subjects were reported as manifesting "no" or "slight"
      improvement (P < 0.001). Adverse effects were few and manageable, with no
      anorexia. Modafinil may be a useful treatment for children with ADHD,
      particularly when anorexia limits use of stimulants.

PMID- 14580658
TI  - Topiramate concentration in saliva: an alternative to serum monitoring.
AB  - This study examines the relationship between serum and saliva topiramate
      concentrations, and attempts to determine if saliva may be a useful alternative
      to serum for therapeutic monitoring. Saliva and blood specimens were collected
      from 31 epilepsy patients (mean age 10.5 +/- 6.0 years; range 2.5 years to 24.8
      years), and topiramate concentrations were determined by fluorescence
      polarization immunoassay. One patient's results were omitted because the saliva
      concentration was below the limit of quantitation of the assay. A strong
      correlation exists between serum and saliva topiramate concentrations (adjusted
      r(2) = 0.97, n = 30, P < 0.0001). The mean fraction of saliva to serum
      concentration is 89.8% +/- 12.1% (range 62.9% to 112.7%). The results of this
      study support the use of saliva as a viable alternative to serum for monitoring
      topiramate therapy. Topiramate concentration in saliva: an alternative to serum
      monitoring.

PMID- 14580659
TI  - Insights into the pathogenesis of cerebral lesions in incontinentia pigmenti.
AB  - We report the case of a neonate with incontinentia pigmenti and seizures on day 4
      of life who underwent magnetic resonance imaging and angiography scanning at 8,
      13, and 21 days of age. The serial magnetic resonance images demonstrated the
      evolution of acute microvascular hemorrhagic infarcts in the periventricular
      white matter in the first week of life. The associated magnetic resonance
      angiogram findings consisted of decreased branching and poor filling of
      intracerebral vessels. This report adds important insights into the nature and
      timing of cerebral lesions in incontinentia pigmenti.

PMID- 14580660
TI  - Rasmussen syndrome and long-term response to thalidomide.
AB  - We report a 13-year-old female who experienced symptoms and signs of Rasmussen
      encephalitis for the first time at the age of 5 years. Various therapeutic
      procedures, including conventional and new antiepileptic drugs, steroids,
      immunoglobulin, plasma exchanges, and partial hemispherectomy, were applied, but
      their results were unsatisfactory. During one of the exacerbations, when the
      patient's life was endangered, thalidomide was administered. Frequency and
      intensity of epileptic seizures were reduced significantly, and the quality of
      her life improved. Except for moderate neutropenia, the other adverse effects
      were not recognized. In our opinion, thalidomide is not a first-choice drug for
      Rasmussen encephalitis but is a good alternative only for cases refractory to
      other well-known and accepted therapeutic procedures.

PMID- 14580661
TI  - Septo-optic dysplasia with congenital hepatic fibrosis.
AB  - This article reports a 7-year-old female with septo-optic dysplasia and
      congenital hepatic fibrosis. She manifested nystagmus and severe
      hepatosplenomegaly. Brain magnetic resonance imaging revealed agenesis of the
      septum pellucidum, optic nerve hypoplasia, pituitary gland stalk hypoplasia, and
      absence of the posterior pituitary gland. She was diagnosed with growth hormone
      deficiency, hypothyroidism, diabetes insipidus, and adrenal insufficiency. Thus,
      this case was regarded as septo-optic dysplasia. No mutation was evident in the
      coding and boundary regions of the homeobox gene HESX1. Percutaneous biopsy of
      the liver demonstrated the presence of broad septa of fibrous tissue containing
      abundant bile ducts without inflammatory cell infiltrates, a finding compatible
      with congenital hepatic fibrosis. Although there is an association between septo
      optic dysplasia and neonatal cholestasis, believed to be related to
      hypopituitarism, this case of septo-optic dysplasia with congenital hepatic
      fibrosis is apparently the first reported in the English literature.

PMID- 14580662
TI  - A patient with epilepsia partialis continua with anti-glutamate receptor epsilon
      2 antibodies.
AB  - This report concerns a 6-year-old female with epilepsia partialis continua.
      Autoantibodies against amino- and carboxyl-terminal regions of the N-methyl-D
      aspartate receptor subunit glutamate receptor epsilon 2 were detected in the
      serum and cerebrospinal fluid. The anti-glutamate receptor epsilon 2 subunit
      antibodies have been demonstrated in the serum and cerebrospinal fluid in some
      patients with chronic progressive epilepsia partialis continua of childhood and
      those with Rasmussen's encephalitis. The patient, however, did not develop any
      neurologic deterioration or intractable seizures. Therefore, anti-glutamate
      receptor epsilon 2 subunit antibodies are not specific for chronic progressive
      epilepsia partialis continua of childhood and Rasmussen's encephalitis.

PMID- 14580663
TI  - Heat stroke in familial dysautonomia.
AB  - A 14-month-old female with familial dysautonomia was referred to the pediatric
      department with high fever (41.6 degrees C), watery diarrhea, and vomiting. A few
      hours later, signs of encephalopathy appeared. Laboratory tests revealed elevated
      levels of lactate dehydrogenase (3500 U/L), aspartate aminotransferase (640 U/L),
      alanine aminotransferase (320 U/L), and creatine kinase (28,420 U/L). The
      diagnosis was heat stroke. Impaired autonomic nervous system function may be
      another risk factor for the development of heat stroke in young children.

PMID- 14580664
TI  - Chiari I malformation with syrinx.
AB  - The Chiari I congenital malformation is characterized by caudal displacement of
      the cerebellar tonsils through the cervical canal. Although this malformation is
      often asymptomatic, coexisting syringomyelia can result in neurologic symptoms.
      We report a case of progressive ataxia with brainstem dysfunction in an
      adolescent female manifesting a severe Chiari I malformation with syrinx. Chiari
      decompression 4 years after initial presentation led to rapid improvement in most
      of her long-term symptoms. This case demonstrates the importance of consideration
      of Chiari I with syringomyelia in the differential diagnosis of progressive
      ataxia and brainstem symptoms.

PMID- 14580665
TI  - Familial pediatric rapidly progressive extrapyramidal syndrome: is it
      Hallervorden-Spatz disease?
AB  - The clinical features of two children of a family with rapidly progressive
      extrapyramidal-pyramidal-dementia complex have been described. Inheritance seems
      most likely to be autosomal recessive. Magnetic resonance imaging results of
      brain were negative. Even so, the authors argued in favor of a diagnosis of
      Hallervorden-Spatz disease because the cases fulfilled the clinical criteria for
      diagnosis of this disease. Apart from the negative magnetic resonance findings,
      the other unusual feature was the early development of levodopa-induced
      dyskinesia. Few conditions need to be considered in the differential diagnosis of
      a childhood-onset rapidly progressive extrapyramidal syndrome. Such conditions
      include Wilson's disease, Hallervorden-Spatz disease (HSD), juvenile form of
      Huntington's disease, juvenile neuronal ceroid lipofuscinosis, early-onset
      Machado-Joseph disease neuroacanthocytosis, storage disorders, and variant form
      of dopa-response dystonias (DRD). Rarer conditions are Leigh's disease, Lafora
      body disease, and dentato-rubro-pallido-luysian atrophy. HSD is a rare disorder
      characterized by progressive extrapyramidal dysfunction and dementia. Onset is
      most commonly in late childhood or early adolescence. The disease can be familial
      or sporadic. When familial, it is inherited recessively and has been linked to
      chromosome 20. Recently, a mutation in the pantothenate kinase (PANK2) gene on
      band 20pl3 has been described in patients with typical HSD. HSD produces typical
      magnetic resonance imaging (MRI) changes in brain, aiding in antemortem
      diagnosis. The typical finding is of bilaterally symmetrical hyperintense signal
      changes in the external segment of globus pallidus, with surrounding
      hypointensity on T(2)-weighted image. These imaging features are fairly
      diagnostic and have been termed the "eye-of-the tiger sign". The hyperintensity
      represents pathologic changes, including gliosis, demyelination, neuronal loss,
      and axonal swelling, and the surrounding hypointensity is caused by loss of
      signal secondary to iron deposition. Described herein are the clinical aspects of
      a family with autosomal recessive inheritance with rapidly progressive
      extrapyramidal-pyramidal-dementia complex but with negative brain MRI results.
      The diagnosis should be considered a variant form of HSD.

PMID- 14580666
TI  - Medical aspects of the minimally conscious state in children.
AB  - The minimally conscious state is a condition of severely altered consciousness in
      which minimal but definite behavioral evidence of self or environmental awareness
      is demonstrated. This must be established on a reproducible or sustained basis by
      one or more of four types of behaviors including simple command-following,
      gestural or verbal 'yes/no' responses, intelligible verbalizations, or purposeful
      behaviors. The minimally conscious state can occur in children and usually is due
      to acquired brain injuries (traumatic and non-traumatic), central nervous system
      degenerative and neurometabolic disorders or congenital or developmental
      disorders. It is assumed that the lower limit of the minimally conscious state
      occurs when patients emerge from a vegetative state. What remains uncertain is
      how we can assess the upper limits, that is the degree of improvement that
      indicates that an individual is no longer minimally conscious. It also is unknown
      if, when and to what extent children can emerge from a minimally conscious state
      and whether their prognosis is better than children who are vegetative. It is
      assumed that the minimally conscious state may become 'permanent' 12 months after
      traumatic brain injury and 3 months after non-traumatic injury although there
      have been no studies that have examined this issue. Medical and rehabilitative
      treatment of children in a minimally conscious state should be provided to
      maintain comfort, reduce complications, and optimize functional recovery.

PMID- 14580667
TI  - Value and limitations of preschool cognitive tests, with an emphasis on
      longitudinal study of children on the autistic spectrum.

PMID- 14580668
TI  - Preschool children with autism spectrum disorders in Taiwan: follow-up of
      cognitive assessment to early school age.
AB  - In this study, we longitudinally followed into childhood a cohort of preschool
      children, initially diagnosed as autistic or non-autistic with developmental
      delay, to evaluate the stability of cognitive assessments performed during the
      preschool period. The consistency in group means and intra-individual stability
      of developmental quotients (DQ) and non-verbal intelligence quotients (IQs) were
      compared for these two groups, which were matched by chronological age, initial
      non-verbal IQ/DQs, initial test given, and length of follow-up interval. The case
      group comprised 16 autistic children with average age at initial assessment of 3
      years 8 months. The control group comprised 16 non-autistic developmental delayed
      children with average age at initial assessment of 3 years 11 months. Mean DQ/non
      verbal IQ at initial assessment was 73.9+/-23.9 for the case group and 80.3+/
      23.2 for the control group. ANOVA yielded no significant effect of time or time x
      diagnosis interaction (F=0.183, P=0.675). The absolute difference in scores and
      group means were equivalent for both groups of children, with no difference in
      patterns of change. Correlations between DQ/non-verbal IQs at initial assessment
      and follow-up were significant and high for the two groups (autistic group:
      r=0.87; control: r=0.77). Intellectual functioning can be a valid measure in
      Taiwanese preschool children with autism, and has an equivalent meaning for
      children with autism and for non-autistic children with developmental delay.
      Though the follow-up period is too short for definite prognostic conclusions to
      be drawn, we think that non-verbal intelligence should be an essential assessment
      for preschool oriental autistic children so that sound expectation and treatment
      plan can be made.

PMID- 14580669
TI  - Age shifts frontal cortical control in a cognitive bias task from right to left:
      part I. Neuropsychological study.
AB  - Two functionally and neurally distinct cognitive selection mechanisms involve the
      prefrontal lobes: those based on internal representations (context dependent) and
      those involving exploratory processing of novel situations (context independent).
      We used a cognitive bias task (CBT) representing contextual reasoning to
      correlate lateralization with age in the frontal lobes. Subjects included 37
      healthy right-handed male children and adolescents (age range, 5-18 years).
      Controls were 19 right-handed men from 20 to 30 years old. A computer-presented
      version of the original card-choice task simplified, modified for children was
      used (modified CBT; mCBT). Simple visual stimuli differed dichotomously in shape,
      color, number, and shading. A target object presented alone was followed by two
      choices from which subjects selected according to preference. Considering all
      four characteristics, similarity between target and subject choice was scored for
      30 trials. A high score implied a context-dependent response selection bias and a
      low score, a context-independent bias. Similarity increased significantly with
      age. The youngest children (5-7 years) scored lower than ages from 11 years to
      adulthood. Between 7 and 9 years, scores began to increase with age to reach an
      adult level by age 13-16. Young children showed context-independent responses
      representing right frontal lobe function, while adolescents and adults showed
      context-dependent responses implicating left frontal lobe function. The locus of
      frontal cortical control in right-handed male subjects thus shifts from right to
      left as cognitive contextual reasoning develops.

PMID- 14580670
TI  - Early development destructive brain lesions and their relationship to epilepsy
      and hippocampal damage.
AB  - Fifty-one consecutive adult patients with epilepsy and early development
      destructive brain lesions were divided into three main groups according to the
      topographic distribution of the lesion on magnetic resonance imaging: hemispheric
      (H) (n=9); main arterial territory (AT) (n=25) and arterial borderzone (Bdz)
      (n=17). Eight (89%) patients from group H presented status epilepticus in the
      first 5 years of life, five of them associated with fever. Seventeen of the 25
      patients from group AT (76%) had an obvious hemiparesis observed early in life.
      In addition, major prenatal events were significantly more common in the group AT
      compared with the other two groups. Among patients from group Bdz, prenatal or
      postnatal events were not identified, except for one patient. Conversely, nine
      patients from group Bdz (60%) showed a history of perinatal complications.
      Hippocampal atrophy (HA) was determined by visual analysis in 74.5% of all
      patients and by volumetry in 92%. The frequency of HA was comparable among
      groups, but patients from group H presented the most severe atrophy and more
      frequent hyperintense T2 hippocampal signal. In conclusion, these three groups of
      patients with early destructive lesions and epilepsy (H, AT and Bdz), appear to
      have distinct pathogenic mechanisms. Our data show that there is a striking
      association of HA with different patterns of neocortical destructive lesions of
      early development. This association seems to be related to a common and
      synchronic pathogenic mechanism. The recognition of the pattern and degree of HA
      among these patients with intractable seizures may influence the surgical
      rationale.

PMID- 14580671
TI  - Congenital monomelic neurogenic disorder with calf muscle hypertrophy.
AB  - An 8-year-old girl had hypertrophy of the right calf muscle since birth, with
      progressive ankle contracture and mild muscle weakness. Her right leg was 3 cm
      shorter than her left. Electromyography and biopsy of the affected muscle showed
      neurogenic changes. She also had neurogenic bladder and spina bifida occulta at
      the S1 level. We believe that the spina bifida was responsible for the neurogenic
      changes in her right calf, but could not find definite evidence for this
      association. Although cases with neurogenic muscle hypertrophy, especially calf
      muscle hypertrophy, have been reported, none of them was congenital or associated
      with spina bifida occulta.

PMID- 14580673
TI  - Tissue-specific expression patterns of the RAGE receptor and its soluble forms--a
      result of regulated alternative splicing?
AB  - The receptor for advanced glycation end products (RAGE) is known to be causally
      involved in a variety of pathophysiological processes, e.g. immune/inflammatory
      disorders, Alzheimer disease, tumors, and abnormalities associated with diabetes
      as arteriosclerosis or disordered wound healing. So far, human cDNAs have been
      characterized encoding for the RAGE receptor and a truncated soluble form lacking
      the transmembrane and the cytosolic domain. The latter form represents a
      naturally occurring competitive inhibitor of signalling pathways induced by the
      membrane-standing RAGE receptor. In order to perform a relative expression
      analysis of both RAGE forms, an RT-PCR experiment was designed allowing the
      simultaneous amplification of corresponding transcripts. We were able to identify
      three novel human RAGE transcripts all encoding truncated soluble forms of RAGE.
      The relative expression ratios for the full-length RAGE transcript to the sum of
      its splice-variants encoding the soluble variants varied strongly among the
      tissues tested. Therefore, the pre-mRNA of RAGE must be subject to regulated
      alternative splicing activated by extracellular cues of yet unknown cellular
      signalling pathways. Thus, as deduced from the occurrence at the RNA level, it
      can be hypothesized that there is a complex RAGE regulation network involving
      isoforms competing for the binding of ligands.

PMID- 14580674
TI  - Sustained expression in mammalian cells with DNA complexed with chitosan
      nanoparticles.
AB  - This work investigates the preparation and in vitro efficiency of chitosan gene
      transfection systems. Chitosan was used to prepare nanoparticles with a size
      range of 40-200 nm as determined using photon correlation spectroscopy (PCS) and
      40-80 nm as determined using transmission electron microscopy (TEM). The ability
      of particles to complex DNA was investigated using gel retardation. Plasmid DNA
      pGL3-Control encoding firefly luciferase and pCH110 encoding beta-galactosidase
      were used as reporter genes. For transfection 293 human embryonal kidney cells
      and Chinese hamster ovary (CHO-K1) cells were used. The expression of luciferase
      was assayed and expressed as relative light units per milligram of protein
      (RLU/mg protein). Results showed that these chitosan particles have potential as
      vectors for the transfer of DNA into mammalian cells. Cellular transfection by
      the chitosan-pGL3-Control particles showed a sustained expression of the
      luciferase gene for about 10 days. Commercial transfection reagents, SuperFect
      and Lipofectin were also used. In contrast to chitosan particles, the duration of
      expression for both SuperFect and Lipofectin was only about 2 days. Agarose gel
      electrophoresis and displacement experiments using polyaspartic acid indicated a
      probable multiple interaction between DNA and chitosan whilst the interaction
      between DNA and the polyamidoamine dendrimer appears to be only ionic
      interaction. No toxic effect on the mammalian cells was seen with chitosan.
      SuperFect and Lipofectin however, were observed to engender marked cytotoxicity.
      Poly-D,L-lactide (PLA) nanoparticles (40-80 nm) and poly-L-lactide (PLLA)
      lamellae (2-6 microm) were also used to load DNA by an adsorption procedure, but
      these failed to give good expression data.

PMID- 14580675
TI  - The regulatory effect of heme on erythroid aminolevulinate synthase in natural
      erythroid cells.
AB  - A major enzymatic pathway in erythroid cells is the eight-step formation of heme,
      starting with the erythroid isoform of aminolevulinate synthase (eALAS). We
      studied the regulation of eALAS synthesis by heme in natural erythroid cells.
      Erythroid cells from mouse blood or bone marrow were incubated with different
      concentrations of heme and labelled with [35S]methionine. This was followed by
      immunoprecipitation of eALAS proteins. Northern blot analysis was done on mRNA
      isolated from bone marrow. Incubation with heme (5-100 muM) was shown to clearly
      inhibit eALAS synthesis in erythroid cells of bone marrow. This inhibitory effect
      of heme could also be observed in peripheral blood cells at higher concentrations
      while the preform of eALAS was rather increased. However, at lower concentrations
      of heme (1-10 microM), eALAS synthesis increased. Northern blot studies argued
      the inhibitory effect was at the posttranscriptional level. Our results suggest
      that the net effect of murine eALAS regulation by heme varies with the degree of
      erythroid differentiation. Heme formation seems to be more tightly controlled in
      the bone marrow (nucleated) cells in order to prevent oxidative cell damage,
      compared to more differentiated erythroid cells.

PMID- 14580676
TI  - Identification of GhMYB109 encoding a R2R3 MYB transcription factor that
      expressed specifically in fiber initials and elongating fibers of cotton
      (Gossypium hirsutum L.).
AB  - Cotton (Gossypium hirsutum L.) fibers are derived from ovule epidermis, which are
      developmentally similar to Arabidopsis trichome where several MYB transcription
      factors have been shown to control their formation. However, little is known
      about the molecular control of cotton fiber initiation. Here we isolated 55
      cotton MYB domain-containing sequences expressed in ovules during fiber
      initiation. Among them, GhMYB109, encoding a R2R3 MYB transcription factor of 234
      amino acids, was found to be structurally related to AtMYBGL1 and AtWER
      controlling the trichome initiation in Arabidopsis thaliana. Southern blot
      hybridization revealed that GhMYB109 is present as a unique-copy gene in cotton
      genome. RNA expression analysis showed that it is specifically expressed in
      cotton fiber initial cells as well as elongating fibers. These results suggested
      that GhMYB109 likely plays a direct role in the initiation and elongation of
      cotton fiber cells.

PMID- 14580678
TI  - tRNA hopping: effects of mutant tRNAs.
AB  - Movement of tRNA and mRNA through the ribosome is coupled. However, selection for
      suppression of a -1 frameshift mutation in Escherichia coli has yielded a class
      of mutant tRNAs that can violate this mechanism and "hop" or disengage from their
      cognate codons and re-pair downstream in the mRNA. Previously described tRNA
      mutants of this class included those with insertions in the anticodon of
      tRNA(Val)1. This report describes further tRNA(Val)1 alterations that enhance
      hopping; these include a novel insertion in the anticodon loop, base
      substitutions in the anticodon stem and a base deletion in the variable loop.
      These results indicate that several different features of a tRNA are important
      for maintaining stable codon-anticodon interactions and coupled movement of tRNA
      and mRNA during the elongation phase of protein synthesis.

PMID- 14580677
TI  - NF-kappaB stimulates Akt phosphorylation and gene expression by distinct
      signaling mechanisms.
AB  - While NF-kappaB may be a downstream target of Akt, Akt can also be regulated by
      NF-kappaB. Elevated expression of p65/RelA stimulates both phosphorylation and
      expression of Akt in NIH3T3 cells and primary endothelial cells. Both effects of
      p65 on Akt are blocked by transcriptional and translational inhibitors,
      suggesting the need for new gene expression. Elevated p65 expression leads to an
      activation of PI-3 kinase and PDK1. Treatment with antisense PDK1
      oligonucleotides reduces PDK1 expression and inhibits the stimulation of Akt
      phosphorylation by p65. Pharmacological inhibition of PI-3 kinase blocks both
      PDK1 and Akt phosphorylation by p65, placing PI-3 kinase upstream of PDK1 in the
      signaling cascade leading to increased Akt phosphorylation. However, neither
      inhibition of PI-3 kinase or of PDK1 affected the ability of p65 to stimulate Akt
      expression, suggesting that distinct mechanisms underlie the two stimulatory
      effects of p65 on Akt. Increased Akt expression by p65 is mediated at the
      transcriptional level.

PMID- 14580679
TI  - Identification and characterisation of a cDNA encoding a 17-kDa isoform of rat
      myelin basic protein.
AB  - The myelin basic proteins (MBPs) are the major proteins of the myelin membrane.
      Multiple MBP mRNAs and protein isoforms are generated by alternative RNA
      splicing. Here we describe the isolation and characterisation of a cDNA clone
      encoding a 17-kDa MBP isoform from the rat (Rattus norvegicus). The isoform is a
      158-amino acid protein consisting of exons 1, 3, 4, 6 and 7 of the MBP gene. RT
      PCR analysis of brain mRNA showed that transcripts encoding the 17-kDa isoform
      were expressed at higher levels early in post-natal development, up to 7 days
      post-partum.

PMID- 14580680
TI  - p53 mutations in betel-associated oral cancer from Thailand.
AB  - The p53 mutations in betel-related oral cancer have been studied but the results
      may be confounded by tobacco and alcohol due to tobacco components in the quid or
      concomitant habits of smoking and drinking. In this study, p53 mutations in
      tumors from Thai betel chewers who neither smoke nor drink were studied in
      comparison to tumors from smokers/drinkers. PCR-SSCP analysis and direct
      sequencing on exon 5-8 were performed. Mutations were detected in 11.8% (8/68) of
      betel-related tumors and 7 of 8 mutations were G:C to A:T transitions. By
      contrast, mutations were found in 22.4% (13/58) of smoking/drinking-related
      tumors with various base substitutions. The results demonstrated different
      mutation profiles between the two exposed groups. The type of mutation detected
      in betel chewers suggested a possible role of areca-specific nitrosamine as a
      causative carcinogen.

PMID- 14580681
TI  - Caspase-independent apoptosis induced by evening primrose extract in Ehrlich
      ascites tumor cells.
AB  - We previously demonstrated that evening primrose extract (EPE) induced apoptosis
      in Ehrlich ascites tumor cells, while mouse embryo fibroblast cells (NIH3T3) used
      as a normal cell model, showed no effect of cell viability by treatment of EPE.
      Furthermore, our results demonstrated the rapid increase in intracellular
      peroxides levels, loss of mitochondrial membrane potential and the release of
      cytochrome c to cytosol, suggesting that the rapid increase in intracellular
      peroxides levels after addition of EPE triggers off induction of apoptosis. In
      this study, we identified that EPE elicited the translocation of Bax to
      mitochondria and apoptosis-inducing factor (AIF) to nuclei, but no activation of
      caspase-3-like protease. We also demonstrated that the rapid EPE-induced increase
      in hydrogen peroxide levels caused the translocation of Bax to mitochondria, and
      then mitochondrial cytochrome c was released. One of the main consequences of
      mitochondrial cytochrome c release is the activation of caspase-3. However, no
      caspase-3 activation was observed. On the other hand, AIF was translocated from
      mitochondria to nuclei. The EPE-induced translocation of AIF was suppressed with
      the addition of catalase, suggesting that the rapid intracellular peroxide levels
      after addition of EPE triggers off induction of apoptosis, which is AIF-mediated
      and caspase-independent.

PMID- 14580682
TI  - 9cUAB30, an RXR specific retinoid, and/or tamoxifen in the prevention of
      methylnitrosourea-induced mammary cancers.
AB  - Studies were performed in female Sprague-Dawley rats to determine the efficacy of
      a new RXR specific retinoid (9cUAB30) when combined with tamoxifen in the
      prevention of mammary cancers and to determine various pharmacokinetic parameters
      of the retinoid. When administered by gavage, 9cUAB30 was rapidly absorbed and
      had a serum t(1/2) of 13.5 h. Since the retinoid was administered in the diet for
      the chemoprevention study, a 28-day study in which 9cUAB30 was given at dose
      levels of 200, 400, and 600 mg/kg diet revealed fairly constant serum levels
      regardless of dose or length of treatment; possibly accounting for the observed
      low toxicity of this compound. When suboptimal doses of 9cUAB30 were given in the
      methylnitrosourea (MNU)-induced mammary cancer model, the following average
      number of mammary cancers were observed: 9cUAB30 (150 mg/kg diet), 4.3; tamoxifen
      (0.4 mg/kg diet), 4.6; 9cUAB30 (150 mg/kg diet)+tamoxifen (0.4 mg/kg diet), 2.6;
      and controls, 6.0. Thus, the combination of the agents resulted in an increased
      effect in preventing mammary cancers; suggesting that cancer cell proliferation
      was inhibited by the compounds blocking different pathways.

PMID- 14580683
TI  - Correlation of redox potentials and inhibitory effects on Epstein-Barr virus
      activation of naphthoquinones.
AB  - As a continuation of our studies using natural and synthetic products as cancer
      chemopreventive agents, we examined the standard redox potentials of some
      naphthoquinones in phosphate buffer at pH 7.2 by means of cyclic voltammetry. A
      definite correlation has been found between the redox potentials and the
      inhibitory effects of the naphthoquinones on Epstein-Barr virus early antigen
      activation. It has been further shown that the correlation can be enhanced by
      introducing an electronic property, i.e. the atomic charges at the C(4) and O(10)
      atoms in the quinone skeleton ring as additional parameters.

PMID- 14580684
TI  - N-butyldeoxynojirimycin inhibits murine melanoma cell ganglioside metabolism and
      delays tumor onset.
AB  - Aberrant ganglioside metabolism is linked to tumor progression. Since ganglioside
      depletion reduced tumorigenicity of MEB4 murine melanoma cells, we studied N
      butyldeoxynojirimycin (NB-DNJ), an imino sugar administered orally to inhibit
      glucosylceramide (GlcCer) synthase in patients with glycosphingolipid storage
      diseases, for effects on MEB4 melanoma tumor cell ganglioside metabolism, cell
      biology, and tumorigenesis. Here we show that 50 microM NB-DNJ reduced MEB4 cell
      GlcCer synthase activity (by 70%), ganglioside synthesis (by 61%), and shedding
      (by 37%) while ceramide concentrations and cell viability were unaffected.
      Partial ganglioside depletion caused a delay in tumor onset but not in tumor
      incidence, possibly because of rapid (48 h) ganglioside recovery. The delay in
      tumor development by NB-DNJ treatment of MEB4 cells provides further support for
      the concept of tumor cell ganglioside metabolism as a therapeutic target in
      cancer.

PMID- 14580685
TI  - Modified arabinoxylan rice bran (MGN-3/Biobran) sensitizes human T cell leukemia
      cells to death receptor (CD95)-induced apoptosis.
AB  - MGN-3, an arabinoxylan extracted from rice bran that is treated enzymatically
      with an extract from Shiitaki mushrooms, is an effective biological response
      modifier that increases NK cell activity, and potentiates the activity of
      conventional chemotherapeutic agents. In this study, we investigated the effect
      of MGN-3 on death receptor-induced apoptosis in the human leukemic HUT 78 cell
      line. HUT 78 cells were pre-treated with MGN-3, and then were incubated with the
      agonistic antibody against death receptor (Fas, CD95). Apoptosis was determined
      by the propidium iodide technique using FACScan. Activation of caspase 3, caspase
      8, and caspase 9 was determined by flow cytometry. Mitochondrial membrane
      potential was measured with DIOC(6) dye using FACScan. Expression of CD95 and Bcl
      2 were measured by flow cytometry. In a dose-dependent manner, MGN-3 enhanced
      anti-CD95 antibody-induced apoptosis. Increased cell death was correlated with
      increased depolarization of mitochondrial membrane potential and increased
      activation of caspase 3, caspase 8, and caspase 9. MGN-3 treatment had no effect
      on the level of expression of CD95, but it caused down regulation of Bcl-2
      expression. These results suggest that MGN-3 increases the susceptibility of
      cancer cells to undergo apoptosis mediated by death ligands, which may be
      relevant for anti-cancer activities.

PMID- 14580686
TI  - alpha-Tocopheryloxybutyric acid enhances necrotic cell death in breast cancer
      cells treated with chemotherapy agent.
AB  - The overexpression of HER-2 receptor contributes to malignant transformation of
      breast cancer cells. We have reported that alpha-tocopheryloxybutyric acid (TE),
      non-antioxidative vitamin E ether derivative inhibits the activation of HER-2
      receptor. The present study was undertaken to estimate if TE could act as a
      useful anti-cancer agent against a breast cancer cell overexpressing HER-2
      receptor (MDA-MB-453 cell line) in combination with a conventional chemotherapy
      agent, adriamycin (ADR). TE enhanced cytotoxic effect of ADR against the human
      breast cancer cell at low doses less than IC(50). The enhancing effect was mainly
      dependent on the elevation of necrotic-like cell death but not apoptotic cell
      death. In conjugation with this event, the inactivation of HER-2 receptor in the
      breast cancer cell was caused by the combination of TE with ADR. These results
      suggest that TE enhances necrotic-like cell death in the breast cancer cells and
      that the cell death relates to the inactivation of HER-2 receptor in the breast
      cancer cells.

PMID- 14580687
TI  - Susceptibility to arsenic-induced hyperkeratosis and oxidative stress genes
      myeloperoxidase and catalase.
AB  - Chronic exposure to inorganic arsenic is known to cause non-melanocytic skin and
      internal cancers in humans. We examined whether genetic susceptibility, as
      determined by single nucleotide polymorphisms -463G-->A and -262C-->T in the
      oxidative stress genes myeloperoxidase (MPO) and catalase (CAT), respectively,
      are associated with the risk of arsenic-induced hyperkeratotic skin lesions
      precursors of skin cancer-in a case-control study in Bangladesh. Carriers of the
      susceptible MPO and CAT genotypes were at elevated risk (OR 2.1 and 95% CI 0.7
      6.2 for MPO; OR 1.9 and 95% CI 0.8-4.7 for CAT) of hyperkeratosis after
      adjustment for arsenic exposure and other covariates. Subjects carrying the high
      risk MPO genotype and with high arsenic exposure were at almost six times (OR
      5.8; 95% CI 1.1-30.1) elevated risk of developing hyperkeratosis as compared to
      those carrying the low-risk genotype and with low arsenic exposure. Similarly,
      highly exposed subjects carrying the high-risk CAT genotype were at more than
      four times (OR 4.6; 95% CI 1.4-15.6) elevated risk of developing hyperkeratosis
      as compared to those carrying the low-risk genotype and with low arsenic
      exposure. Our findings, although based on small numbers, suggest that the
      oxidative stress genes MPO and CAT may influence the risk of arsenic-induced
      premalignant hyperkeratotic skin lesions.

PMID- 14580688
TI  - Common malignancy-associated regions of transcriptional activation (MARTA) in
      human prostate, breast, ovarian, and colon cancers are targets for DNA
      amplification.
AB  - Transcriptional co-regulation of sets of adjacent genes at the chromosomal domain
      level has been demonstrated recently in eukaryotes, supporting the idea that
      genomes are divided into regions of clustered expression of groups of adjacent
      genes. The mechanism underlying this phenomenon and its significance for human
      pathology is not yet known. Systematic analysis of the chromosomal positions of
      cancer-associated transcripts for prostate, breast, ovarian, and colon tumors
      identified short segments of human chromosomes that appear to represent a common
      target for transcriptional activation in major epithelial malignancies in human
      (1q21-q23 [140-160 Mbp]; 11q12-q13 [62-69 Mbp]; 12q13 [49-58 Mbp]; 17q21 [37-50
      Mbp]; 17q23-q25 [70-81 Mbp]; 19p13 [0.2-19 Mbp]; Xq28 [147-153 Mbp]). At least
      some of these cancer-associated MARTAs correspond well to the regions of
      recurrent amplification in human cancer and seemed to be targets for DNA
      amplifications in established cancer cell lines.

PMID- 14580689
TI  - Production of spindle cell carcinoma by transduction of H-Ras 61L into
      immortalized human mammary epithelial cells.
AB  - Human mammary epithelial cells (HMEC) were immortalized by serial passaging
      through senescence (M0) and subsequent transduction with the catalytic subunit of
      the human telomerase gene (hTERT). These cells acquired multiple non-random
      cytogenetic abnormalities with lengthy passaging in vitro, but are still not
      tumorigenic in irradiated nude mice and cannot grow in soft agar. Transduction,
      of late passage immortal HMEC from a single donor, with a retroviral vector
      containing the mutant autoactive H-Ras 61L gene, enabled immortal HMEC to acquire
      anchorage independent growth properties. Three colonies were picked and all three
      were found to be tumorigenic. One colony exclusively produced epithelial tumors
      in nude mice, but the other two colonies gave rise exclusively to malignancies in
      which the cells displayed a spindle morphology. In this paper we describe the
      characteristics of the tumors arising from one of these 'spindle colonies'. These
      tumors were strongly positive for vimentin staining and virtually negative for
      pan-cytokeratin staining, on immunohistochemistry. Cytogenetic analysis of the
      cells derived from these tumors confirmed that they were derived from the
      original cultured, immortalized mammary cells. We conclude that the HMEC have
      undergone metaplastic transformation due to the high levels of H-Ras 61L and
      telomerase activity that they display, and the derived tumors are best described
      as spindle cell carcinomas.

PMID- 14580690
TI  - Hyperthermia enhances tumor necrosis factor alpha-induced apoptosis of a human
      gastric cancer cell line.
AB  - We have investigated the effects of hyperthermia on the apoptosis induced by
      tumor necrosis factor alpha (TNF-alpha). Confluent monolayers of human gastric
      cancer cell line MKN45 were either treated or untreated with hyperthermia for 1
      h. The cells were subsequently stimulated with TNF-alpha. A 24-h incubation with
      TNF-alpha did not affect cell viabilities; however, pretreatment with
      hyperthermia significantly enhanced the level of apoptosis induced by TNF-alpha.
      Pretreating MKN45 cells with hyperthermia (42.0 degrees C) significantly
      inhibited the TNF-alpha-induced increase in the binding activity of NF-kappaB to
      DNA. This study suggests that hyperthermia can inhibit the TNF-alpha-induced NF
      kappaB activation and that hyperthermia renders human gastric cancer cells
      susceptible to the TNF-alpha-induced apoptosis, possibly via inhibition of the NF
      kappaB pathway.

PMID- 14580691
TI  - Loss of E-cadherin expression correlates with poor differentiation and invasion
      into adjacent organs in gastric adenocarcinomas.
AB  - Perturbation in E-cadherin expression leads to loss of cellular adhesion with
      possible consequence of cellular transformation and tumor progression. The aims
      of this study were to determine E-cadherin expression in each subtype of gastric
      cancer classified by different classification systems, and to investigate the
      role of E-cadherin in cell differentiation, cancer invasion and metastasis.
      Expression of E-cadherin was analyzed in 84 patients with gastric adenocarcinoma
      by immunohistochemistry and correlated with clinicopahotlogical parameters. Our
      results showed loss of E-cadherin expression in 0% (0/3), 20.0% (9/45), 48%
      (15/31), 100% (3/3) and 100% (2/2) of papillary, tubular, poorly differentiated,
      signet-ring cell, and mucinous adenocarcinoma by Japanese histological
      classification. The reduction of E-cadherin expression was inversely correlated
      with the grade of differentiation. According to the histological classification
      of Lauren and Ming, the frequency of lost E-cadherin expression was higher in
      diffuse type (65%) and infiltrative type (64%) gastric cancer than in intestinal
      type (20%, P<0.001) and expanding type cancer (22%, P<0.001), respectively. The
      loss of E-cadherin expression was significantly associated with tumor invasion
      (P<0.05). Furthermore, there was a borderline association between the loss of E
      cadherin expression and poor survival (P=0.109). These data demonstrated a
      striking correlation between E-cadherin expression and the differentiation of
      gastric carcinoma. The loss of E-cadherin expression may contribute to gastric
      cancer invasion to adjacent organs.

PMID- 14580692
TI  - Blockade of constitutively activated Janus kinase/signal transducer and activator
      of transcription-3 pathway inhibits growth of human pancreatic cancer.
AB  - Constitutive activation of signal transducer and activator of transcription
      (Stat) proteins has been demonstrated in a wide variety of malignancies. In this
      study, we elucidated the significance of Janus kinase (JAK) and the downstream
      transcription factor Stat3 signals on malignant potentials of pancreatic cancer.
      Electrophoretic mobility shift assay and immunohistochemical analysis revealed
      that Stat3 was constitutively activated in subsets of human pancreatic cancer
      tissues and cell lines (Panc1, Kp4, AsPC-1, BxPC-3). A JAK-specific inhibitor,
      tyrphostin AG490, markedly inhibited Stat3 activation and expression of cyclin
      D1, bcl-xL and vascular endothelial growth factor mRNAs estimated by RT-PCR, as
      followed by growth arrest (6.3-21.3% vs controls; P<0.001) of pancreatic cancer
      cells. Inactivation of Stat3 by dominant-negative Stat3 adenovirus partly
      suppressed the growth of pancreatic cancer cells on day 4 post-inoculation
      (P<0.05) but not the expression of these mRNAs. These results indicate that
      activation of the JAK/Stat3 signaling pathway plays an important role in the
      progression of pancreatic cancer and that blockade of JAK/Stat3 signals may
      provide a novel therapeutic strategy for pancreatic cancer.

PMID- 14580695
TI  - Role of the orbital prefrontal cortex in choice between delayed and uncertain
      reinforcers: a quantitative analysis.
AB  - 'Inter-temporal choice' refers to choice between two or more outcomes that differ
      with respect to their sizes, delays, and/or probabilities of occurrence.
      According to the multiplicative hyperbolic model of inter-temporal choice, the
      value of a reinforcer increases as a hyperbolic function of its size, and
      decreases as a hyperbolic function of its delay and the odds against its
      occurrence. These functions, each of which contains a single discounting
      parameter, are assumed to combine multiplicatively to determine the overall value
      of the reinforcer. The model gives rise to a quantitative methodology for
      analysing inter-temporal choice, based on a family of linear null equations which
      describe performance under conditions of indifference, when the values of the
      reinforcers are assumed to be equal. This approach was used to examine the effect
      of lesions of the orbital prefrontal cortex (OPFC) on inter-temporal choice in
      rats. Under halothane anaesthesia, rats received injections of the excitotoxin
      quinolinate into the OPFC or sham lesions. They were trained to press two levers
      (A and B) for food-pellet reinforcers in discrete-trials schedules. In free
      choice trials, a press on A resulted in delivery of a pellet after a delay d(A)
      with a probability P=0.5; a press on B resulted in delivery of a pellet with a
      probability P=1 after a delay d(B). d(B) was increased progressively across
      successive blocks of six trials in each session, while d(A) was manipulated
      systematically across phases of the experiment. The indifference delays, d(B(50))
      (value of d(B) corresponding to 50% choice of B) was estimated for each rat in
      each phase. Linear functions of d(B(50)) versus d(A) were derived, and the
      parameters of the function compared between the groups. In both groups, d(B(50))
      increased linearly with d(A). The slope of the linear function was significantly
      steeper in the lesioned group than in the sham-lesioned group, whereas the
      intercept did not differ significantly between the groups. Analysis based on the
      relevant null equation indicated that the lesion of the OPFC increased the rate
      of both delay and odds discounting. Possible implications of the results for
      interpreting the effects of OPFC lesions on inter-temporal choice behaviour in
      man are discussed.

PMID- 14580696
TI  - Effects of free-food deliveries and delays on choice under concurrent-chains
      schedules.
AB  - Pigeons responded on a concurrent-chains schedule with two equal variable
      interval (VI) schedules as initial links and delays to food of 3 and 12s as the
      two terminal links. In even-numbered sessions, no other reinforcement schedule
      was present, and all pigeons showed a strong preference for the response key that
      had the shorter, 3-s terminal-link delay. In odd-numbered sessions, the initial
      links were interrupted at random times by one of three different types of events.
      When the interruptions were immediate food deliveries, the response percentages
      increased on the key that had the 3-s delay. When the interruptions were 30-s
      delays followed by food, the response percentages remained approximately
      unchanged. When the interruptions were 30-s delays with no food, the response
      percentages decreased. The results were used to compare the predictions of
      different mathematical models of concurrent-chains performance. The results
      favored models that assume that preference is determined by the relative amount
      of advantage that is gained when a terminal link is entered.

PMID- 14580697
TI  - Effects of reinforcer magnitude on an animal model of impulsive behavior.
AB  - The effects of altering sucrose solution concentration on discounting of delayed
      rewards in rats were examined. Five different delays were used (0, 1, 2, 4, and
      8s) and three different sucrose solution concentrations (3, 10, and 30%). It was
      hypothesized that high value sucrose solution concentrations would be discounted
      less than low value sucrose solution concentrations. The results indicated that
      the rats discounted the 30% sucrose solution concentration at a higher rate than
      the 3 or 10% sucrose solution concentration, a finding that apparently
      contradicted the hypothesis that higher value sucrose solution concentrations
      would be discounted less than lower value sucrose solution concentrations.
      However, a follow up experiment indicated that the 3 and 10% sucrose solution
      concentrations were preferred over the 30% concentration. Thus the results of
      Experiment 1 can be interpreted as supporting the hypothesis that high valued
      sucrose solution concentrations are discounted less than lower valued sucrose
      solution concentrations.

PMID- 14580698
TI  - Effects of multiple delayed rewards on delay discounting in an adjusting amount
      procedure.
AB  - It has been suggested that when the delivery of several rewards is separated in
      time, e.g. one reward immediately and a second reward a few moments later, the
      value of an alternative that includes these "bundled" rewards will be the sum of
      the hyperbolic discount functions of the individual rewards. The current study
      examined this hypothesis using an adjusting amount procedure. In this procedure,
      rats chose between a delayed food alternative and an immediate food alternative,
      where the amount of immediate food altered according to each rat's choices. The
      size of the immediate reward when rats were indifferent between the delayed and
      immediate alternatives indexed the value of the delayed alternative. Discount
      functions describing the relationship between the indifference points and the
      delay to food were created for conditions in which the delay alternative
      consisted of a single reward (150mul of sucrose solution) delayed by 0, 2, 4, 8,
      or 16s following the reinforced response. These functions were used to predict
      the indifference points in other conditions for which an additional 150mul of
      sucrose solution was delivered at 0, 4, 8, or 16s following the reinforced
      response. The model fit the data well. However, there were systematic deviations
      that suggested animals were sensitive to the context within which delays were
      presented, in addition to the delays themselves. That is, preference for the
      delayed alternative was lower than predicted when the delay to the additional
      reward was long (8 or 16s) and higher than the predicted values when it was short
      (0 or 4s).

PMID- 14580699
TI  - Measurement of delay discounting using trial-by-trial consequences.
AB  - DELAY DISCOUNTING IN HUMANS WAS INVESTIGATED USING THREE DIFFERENT PROCEDURES: a
      frequently used discounting procedure with hypothetical rewards and delays; a
      procedure with hypothetical rewards and delays compressed down to much smaller
      values; and a contingent procedure in which each choice had a direct consequence.
      In the contingent procedure, on every trial, participants actually experienced
      the delay and obtained the reward amount associated with their choice. Each
      participant was exposed to all three procedures. Orderly temporal discounting
      patterns were obtained in all three procedures and described well by a hyperbolic
      model. Comparisons of the data revealed patterns unique to each procedure. The
      distributions of the discounting measures differed across the three procedures.
      In the contingent procedure, several subjects showed no discounting, e.g.
      complete self-control. Procedural factors in studies of impulsivity are
      discussed, and suggestions are offered for experiments in which the contingent
      discounting procedure may prove useful.

PMID- 14580700
TI  - Discounting of delayed hypothetical money, alcohol, and food.
AB  - For drug-dependent individuals, drugs of abuse that are delayed in time are
      discounted more steeply than money delayed in time in a hypothetical choice task.
      The reasons for this finding are not clear. This study examined whether steep
      discounting of drugs relative to money might be related to the function of drugs
      as primary/consumable reinforcers and money as a conditioned/non-consumable
      reinforcer. Twenty adults with no self-reported problems with money, alcohol, or
      food participated. They indicated their preferences for three hypothetical
      outcome types: delayed versus immediate money, delayed versus immediate food, and
      delayed versus immediate alcohol. Both the hyperbolic decay model and area under
      the curve analysis showed that money was discounted less steeply than alcohol or
      food, but that alcohol and food were discounted similarly. This finding
      replicates previous results showing that people without drug abuse problems show
      steep discounting of alcohol. Furthermore, this finding suggests that alcohol may
      be steeply discounted as part of a general process involving primary/consumable
      reinforcers, not necessarily because it is a drug.

PMID- 14580701
TI  - Temporal discounting predicts individual competitive success in a human analogue
      of group foraging.
AB  - Twenty groups of college undergraduates (N=9-12) participated in a discrete
      trials analogue of group foraging in which points, exchangeable for course
      credit, were the resource to be acquired. Group matching of foragers to patch
      resource availability was well described by the generalized Ideal Free
      Distribution, with undermatching (imperfect sensitivity to resource
      differentials) the norm. Individuals differed on several measures of competitive
      success, and a measure of temporal discounting (TD) accounted for a significant
      proportion of the variance in these measures. Tendencies in switch patterns and
      visit durations differed for the most-impulsive and least-impulsive individuals
      in a fashion that was consistent with a TD interpretation. When competitive
      weights, defined in terms of TD scores, were substituted for counts of
      individuals in the generalized Ideal Free Distribution, group-matching slopes
      more closely approximated perfect sensitivity than in standard analyses. This was
      true for groups incorporating all impulsive individuals, all non-impulsive
      individuals, or a broad range of TD scores. The results suggest that well
      understood individual psychological processes are associated with competitive
      ability in group choice.

PMID- 14580702
TI  - Delay and probability discounting as related to different stages of adolescent
      smoking and non-smoking.
AB  - This study examined relations between different patterns of adolescent cigarette
      smoking and discounting of monetary rewards due to delay (delay discounting) and
      probabilistic uncertainty (probability discounting). The study also examined the
      relation between smoking and the number of peer friends who smoke and level of
      parent education. Participants were 55 adolescents (28 females) between 14 and 16
      years of age who were categorized according to the following patterns of smoking
      behavior: "never smokers" (n=19; 10 females) who had not tried even one
      cigarette; "triers" (n=17; 9 females) who had recently tried cigarettes for the
      first time; and "current smokers" (n=19; 9 females) who smoked a minimum of one
      cigarette every week for at least 6 months prior to data collection. It was
      hypothesized that current smokers would discount more than those who had never
      smoked. No specific hypotheses were made for participants only trying cigarettes.
      Unexpectedly, results indicated no differences in discounting between the current
      smokers and never smokers. However, the trier group discounted probabilistic
      rewards significantly more than the never- and current-smoker groups. Also,
      triers and current smokers both reported having more friends who smoked than
      never smokers, and fathers of never smokers had significantly more education than
      fathers of either triers or current smokers. These results suggest that impulsive
      discounting may be more related to adolescents trying cigarettes than to their
      becoming regular smokers, whereas number of peer friends who smoke and parent
      level of education seem to differentiate between those who have smoked to some
      extent (triers and current smokers) and those who have not even tried cigarettes
      (never smokers).

PMID- 14580703
TI  - Pathological gambling severity is associated with impulsivity in a delay
      discounting procedure.
AB  - Research and clinical expertise indicates that impulsivity is an underlying
      feature of pathological gambling. This study examined the extent to which
      impulsive behavior, defined by the rate of discounting delayed monetary rewards,
      varies with pathological gambling severity, assessed by the South Oaks Gambling
      Screen (SOGS). Sixty-two pathological gamblers completed a delay discounting
      task, the SOGS, the Eysenck impulsivity scale, the Addiction Severity Index
      (ASI), and questions about gambling and substance use at intake to outpatient
      treatment for pathological gambling. In the delay discounting task, participants
      chose between a large delayed reward (US $1000) and smaller more immediate
      rewards (US $1-$999) across a range of delays (6h to 25 years). The rate at which
      the delayed reward was discounted (k value) was derived for each participant and
      linear regression was used to identify the variables that predicted k values.
      Age, gender, years of education, substance abuse treatment history, and cigarette
      smoking history failed to significantly predict k values. Scores on the Eysenck
      impulsivity scale and the SOGS both accounted for a significant proportion of the
      variance in k values. The predictive value of the SOGS was 1.4 times that of the
      Eysenck scale. These results indicate that of the measures tested, gambling
      severity was the best single predictor of impulsive behavior in a delay
      discounting task in this sample of pathological gamblers.

PMID- 14580704
TI  - Is discounting impulsive?. Evidence from temporal and probability discounting in
      gambling and non-gambling college students.
AB  - Discounting tasks were used to evaluate whether gambling and non-gambling college
      students (categorized based on their scores on the South Oaks Gambling Screen)
      differed in the degree to which they discounted delayed and probabilistic
      rewards. Hyperbola-like functions provided equally good descriptions of
      discounting in both groups. Both groups discounted large delayed amounts less
      steeply than small delayed amounts, whereas both groups discounted large
      probabilistic amounts more steeply than small probabilistic amounts. Gamblers
      discounted probabilistic rewards less steeply than non-gamblers, suggesting that
      gamblers are impulsive in the sense that they are less affected by risk than non
      gamblers. However, gamblers did not discount delayed rewards more steeply than
      non-gamblers. The results argue against the view that impulsivity is a general
      trait that includes both an inability to delay gratification and a tendency to
      take risks.

PMID- 14580706
TI  - Impetuosity and discounting: From basic process to human welfare.

PMID- 14580705
TI  - Uncertainty as wealth.
AB  - Emotional satisfaction cannot be increased above "normal"-the same normal as the
      caveman's-for any length of time, but the wealth and consumption style of modern
      civilization may systematically reduce some people's satisfaction below normal.
      Hyperbolic discounting of delayed, expected rewards suggests causes for this
      reduction in humans, and for how we often respond to it, while conventional
      exponential discounting does not. Hyperbolic discounting has been well
      demonstrated by four experimental routes; and there is moderate evidence that it
      motivates impulse control by an intertemporal bargaining technique, proposed as
      the mechanism of willpower.A theoretical model is described in which emotion is a
      reward-dependent behavior rather than a stimulus-bound respondent. Positive
      emotion is then limited by premature satiation of the appetite for it, a
      relentless process motivated by the impatience that is described by hyperbolic
      discount curves. This satiation can be restrained only by using adequately rare
      and unpredictable occasions as cues for the emotion. Willpower not only is
      helpless against the urge for premature satiation, but it exacerbates the
      satiation problem by making anticipation more thorough. The result is an
      asymmetrical contest between systematic attempts to vouchsafe satisfying events
      and impetuous attempts to put them at risk. Despite their adversarial
      relationship, both may to some extent be in the person's long range interest.

PMID- 14580707
TI  - Docosahexaenoic acid: membrane properties of a unique fatty acid.
AB  - Docosahexaenoic acid (DHA) with 22-carbons and 6 double bonds is the extreme
      example of an omega-3 polyunsaturated fatty acid (PUFA). DHA has strong medical
      implications since its dietary presence has been positively linked to the
      prevention of numerous human afflictions including cancer and heart disease. The
      PUFA, moreover, is essential to neurological function. It is remarkable that one
      simple molecule has been reported to affect so many seemingly unrelated
      biological processes. Although details of a molecular mode of action remain
      elusive, DHA must be acting at a fundamental level common to many tissues that is
      related to the high degree of conformational flexibility that the multiple double
      bonds have been identified to confer. One likely target for DHA action is at the
      cell membrane where the fatty acid is known to readily incorporate into membrane
      phospholipids. Once esterified into phospholipids DHA has been demonstrated to
      significantly alter many basic properties of membranes including acyl chain order
      and "fluidity", phase behavior, elastic compressibility, permeability, fusion,
      flip-flop and protein activity. It is concluded that DHA's interaction with other
      membrane lipids, particularly cholesterol, may play a prominent role in
      modulating the local structure and function of cell membranes.

PMID- 14580708
TI  - Temporary membrane distortion of vascular smooth muscle cells is responsible for
      their apoptosis induced by platelet-activating factor-like oxidized phospholipids
      and their degradation product, lysophosphatidylcholine.
AB  - To obtain information about the mechanism of apoptosis induced by oxidized low
      density lipoproteins (oxLDL) in atherosclerotic plaques, we examined the effects
      of lysophosphatidylcholine (LPC) and platelet-activating factor (PAF)-like lipids
      (PAF-LL), which can be derived from oxLDL, on rat vascular smooth muscle cells
      (VSMC). All the lipids with different structures examined induced apoptosis of
      VSMC, so we studied the mechanism of induction of apoptosis by LPC. LPC-induced
      apoptosis was inhibited by alpha-tocopherol (alpha-T) and cholesterol (Chol), but
      not by other antioxidants such as palmitoyl ascorbic acid and PAF receptor
      antagonist. The cells temporarily became spherical and highly permeable before
      induction of apoptosis, and their change in shape was prevented by alpha-T and
      Chol. From these results, we suggest that the apoptosis induced by oxLDL-derived
      phospholipids in VSMC is caused by temporary membrane distortion, not through
      specific receptors.

PMID- 14580709
TI  - Pluronic L81 affects the lipid particle sizes and apolipoprotein B conformation.
AB  - The chylomicron assembly has been proposed to involve the core expansion of
      apolipoprotein B (apoB)-containing primordial lipoproteins by fusing with
      triglyceride-rich lipid droplets. We examined the effects of an inhibitor of
      chylomicron secretion, Pluronic L81, on triolein-phosphatidylcholine emulsions
      and low density lipoproteins (LDL) which were used for the models of lipid
      droplets and primordial lipoproteins, respectively. We showed by dynamic light
      scattering that the sizes of lipid emulsions and LDL were increased in the
      presence of Pluronic L81. The binding of apoB-100 to lipid emulsions was enhanced
      by Pluronic L81. CD and fluorescence lifetime measurements revealed that Pluronic
      L81 altered the secondary structure of apoB-100 with an increased local
      hydration. The proper hydrophilic-to-hydrophobic balance of Pluronic L81 is
      important for these actions. It is proposed that Pluronic L81 inhibits the
      secretion of chylomicrons by leading the excess core expansion of the primordial
      lipoproteins and the conformational modification of apoB.

PMID- 14580710
TI  - Facile synthesis of (Z)-tetracos-5-enoic acid and racemic cis-4-(2
      octadecylcyclopropane-1-yl)-butanoic acid.
AB  - (Z)-tetracos-5-enoic acid and racemic cis-4-(2-octadecylcyclopropane-1-yl)
      butanoic acid have been prepared from 1-eicosene by a new facile route. Periodic
      acid cleavage of the epoxide of 1-eicosene gave nonadecanal which was condensed
      with 4-carboxybutyltriphenylphosphonium bromide to give predominately (Z)
      tetracos-5-enoic acid. Simmons-Smith type cyclopropanation of (Z)-tetracos-5
      enoic acid gave a minor proportion of racemic cis-4-(2-octadecylcyclopropane-1
      yl)-butanoic acid accompanied by major amounts of its methyl ester.

PMID- 14580711
TI  - Temperature-dependence of the solubilization of dipalmitoylphosphatidylcholine
      (DPPC) by the non-ionic surfactant Triton X-100, kinetic and structural aspects.
AB  - Most of the studies on the solubilization of model membranes conducted thus far
      involved model membranes made of liquid-crystalline phospholipids. Relatively
      little is known on the influence of temperature and of the phase of the lipid
      bilayers on their solubilization by detergents. The aim of the present study was
      to gain knowledge about the temperature and phase dependence of the
      solubilization of phospholipid bilayers by the non-ionic detergent Triton X-100
      (TR). Detailed investigation of the kinetics of the solubilization of
      dipalmitoylphosphatidylcholine (DPPC), as well as of
      palmitoyloleoylphosphatidylcholine (POPC) by TR at different temperatures reveals
      that: (i) solubilization of DPPC is a relatively slow process, especially below
      Tm. This means that in order to prevent misleading conclusions it is important to
      monitor the solubilization after a steady state is established. (ii) Both the
      steady state structure and size of DPPC/TR aggregates and the kinetics of
      solubilization depend on temperature. (iii) The TR concentration required for
      solubilization of POPC bilayers is an increasing function of temperature,
      although no phase change of bilayers occurs in the studied temperature range.
      (iv) Detailed studies of the temperature-induced changes of the aggregates
      present in DPPC/TR or POPC/TR mixtures suggest that the state of aggregation at
      any temperature above 23 degrees C represents equilibrium. By contrast, for
      DPPC/TR mixtures at 4 degrees C all the processes are very slow, which
      complicates the interpretation of results obtained through the common practice of
      studying "rafts" by investigating detergent-resistant membranes.

PMID- 14580712
TI  - Linkage identity is a major factor in determining the effect of PEG-ylated
      surfactants on permeability of phosphatidylcholine liposomes.
AB  - The permeability effects induced by single-chained and double-chained
      poly(ethylene glycol)-surfactants were investigated by measuring the leakage of
      the fluorescent dye 5(6)-carboxy fluorescein from EPC liposomes. The standard
      incorporated amount of the surfactants was 5 mol%. Depending on the size of the
      poly(ethylene glycol) chain and especially on the type of linkage between the
      polymer and the hydrophobic moiety different leakage profiles were obtained. The
      presence of a long PEG-polymer resulted in a slower leakage compared with a short
      analogue. More importantly, the linkage identity was decisive for whether an
      overall reduction or increase in permeability was obtained. When the hydrocarbon
      chains were attached to the PEG chain via an ether or an ester the leakage
      increased compared to pure EPC liposomes. In contrast, if the link was an amide,
      the leakage was significantly reduced. This effect is assumed to originate from
      headgroup-headgroup interactions, and most probably hydrogen bonding, between
      amide and phosphate groups of the PEG-surfactant and the EPC, respectively.

PMID- 14580713
TI  - Analysis of the lipid composition of bull spermatozoa by MALDI-TOF mass
      spectrometry--a cautionary note.
AB  - In this study we demonstrated the combination of MALDI-TOF MS and TLC as a fast
      and powerful tool to investigate the phospholipid (PL) composition of organic
      extracts of bull spermatozoa. Since phosphatidylcholine (PC) is the dominant PL
      species, an adequate resolution of MALDI-TOF spectra for sphingomyelin (SM) or
      phosphatidylethanolamine (PE) was achieved only after previous PL separation by
      TLC. We found a poor diversity especially for PE and PC, mainly containing ether
      linked fatty acids which were 1-palmityl-2-docosahexaenoyl-PL and the
      corresponding alkenyl-acyl compound (plasmalogen) 1-palmitenyl-2-docosahexaenoyl
      PL. For PC, both lipids were quantified after phospholipase A2 digestion to
      represent 44.2 and 37.2%, respectively, of the total PC. In contrast, the diacyl
      PC content of bull spermatozoa was comparatively low (18.6% of total PC). In the
      presence of trifluoroacetic acid (TFA), which is routinely added to the MALDI-TOF
      matrix to improve the signal to noise ratio, a high lysophospholipid (LPL)
      content was detected in the PL extracts of bull spermatozoa, whereas TLC did not
      reveal significant amounts of LPL. The TFA mediated hydrolysis of the acid-labile
      alkenyl-acyl PL to the corresponding LPL was shown to cause this discrepancy.
      This assumption was verified by analysing the PL composition by MALDI-TOF MS
      before and after (i) digestion of sperm cell lipids with phospholipase A2 and
      (ii) exposition of spermatozoa to HCl fumes. We conclude that the analysis of
      samples containing alkenyl-acyl-PL by MALDI-TOF has to be performed with great
      caution.

PMID- 14580714
TI  - Peroxidation of liposomal palmitoyllinoleoylphosphatidylcholine (PLPC), effects
      of surface charge on the oxidizability and on the potency of antioxidants.
AB  - Peroxidation of membrane phospholipids is an important determinant of membrane
      function. Previously we studied the kinetics of peroxidation of the
      polyunsaturated fatty acid (PUFA) residues in model membranes (liposomes) made by
      sonication of palmitoyllinoleoylphosphatidylcholine (PLPC). Since most
      biomembranes are negatively-charged, we have now studied the effect of negative
      surface charge on the kinetics of peroxidation of liposomes made of PLPC and 9%
      of one of the negatively-charged phospholipids phosphatidylserine (PS) or
      phosphatidic acid (PA). Peroxidation was initiated by either CuCl2 or AAPH and
      continuously monitored spectrophotometrically. The following results were
      obtained: (i) The negative charge had only a slight effect on AAPH-induced
      peroxidation, but accelerated markedly copper-induced peroxidation of the
      liposomes, probably by increasing the binding of copper to the membrane surface.
      (ii) Ascorbic acid (AA) inhibited AAPH-induced but promoted copper-induced
      peroxidation in all the studied liposomes, probably by enhancing the production
      of free radicals upon reduction of Cu(II) to Cu(I). (iii) alpha-tocopherol (Toc)
      inhibited AAPH-induced peroxidation in all the studied liposomes, whereas the
      effect of tocopherol on copper-induced peroxidation varied from being pro
      oxidative in PA-containing liposomes, to being extremely anti-oxidative in PS
      containing liposomes, even at very low tocopherol concentrations. The
      significance of the latter unusual protective effect, which we attribute to
      recycling of tocopherol by a PS-Cu complex, requires further investigation.

PMID- 14580715
TI  - Comparative study of the product components of lipid oxidation in aqueous and
      organic systems.
AB  - Ethyl esters and phosphatidylcholines (PCs) of polyunsaturated fatty acids
      (PUFAs) were oxidized in organic solvents, aqueous emulsions, and liposomes in
      the presence of a radical inducer. Oxidation products and the positional
      distribution of monohydroperoxide (MHP) were determined by gas chromatography
      mass spectrometry (GC-MS) analysis. The total amount of the oxidation products,
      of PUFA ethyl esters and PCs in organic solvents, increased with an increase in
      the number of bis-allylic positions. However, the opposite results were obtained
      in an aqueous emulsion and liposomes. The distribution pattern of MHPs obtained
      from oxidation of the linolate and alpha-linolenate showed little difference
      between a chloroform solution and an aqueous emulsion or liposomes. However,
      there were differences between these systems with the arachidonate, the
      icosapentaenoate, and docosahexaenoate. These results may be due to the different
      rate of hydrogen abstraction from bis-allylic positions in the fatty acid
      moieties, and/or 1,3-cyclization of hydroperoxides in the systems.

PMID- 14580717
TI  - The N-terminus of human prolactin modulates its biological properties.
AB  - The N-terminus is the most divergent region within the prolactin (PRL)/placental
      lactogen (PL)/growth hormone (GH) family. Since all of these ligands are able to
      activate the lactogen receptor, it has been usually assumed that the N-terminus
      plays no major role in biological actions of any family member. In this study, we
      generated several analogs of human PRL in which the N-terminus was truncated by 9
      and iteratively up to the 14 first residues. Truncation did not alter protein
      folding, and it even decreased the formation of PRL aggregates that appear during
      the purification of refolded protein. Removal of the entire N-terminal loop (14
      residues) decreased the affinity for the receptor by two-three-fold, and reduced
      the ability of the hormone to activate the human lactogen receptor. In contrast,
      removal of 13 or less residues improves receptor activation since these analogs
      are able to produce supra-maximal activities in a transcriptional bioassay, or in
      proliferation assays exhibit dose-response curves that are less bell-shaped,
      which reflects enhanced stabilization of receptor dimers. Altogether, these data
      suggest that the N-terminus of PRL is actually slightly detrimental to
      bioactivity, but may be required for other properties of the hormone.

PMID- 14580716
TI  - Estrogen inhibits cell cycle progression and retinoblastoma phosphorylation in
      rhesus ovarian surface epithelial cell culture.
AB  - Estrogen promotes the growth of some ovarian cancer cells at nanomolar
      concentrations, but has been shown to inhibit growth of normal ovarian surface
      epithelial (OSE) cells at micromolar concentrations (1 microg/ml). OSE cells
      express the estrogen receptor (ER)-alpha, and are the source of 90% of ovarian
      cancers. The potential sensitivity of OSE cells to estrogen stresses the
      importance of understanding the estrogen-dependent mechanisms at play in OSE
      proliferation and transformation, as well as in anticancer treatment. We
      investigated the effects of estradiol on cell proliferation in vitro, and
      demonstrate an intracellular locus of action of estradiol in cultured rhesus
      ovarian surface epithelial (RhOSE) cells. We show that ovarian and breast cells
      are growth-inhibited by micromolar concentrations of estradiol, and that this
      inhibition correlates with estrogen receptor expression. We further show that
      normal rhesus OSE cells do not activate ERK or Akt in response to estradiol, nor
      does estradiol block the ability of serum to stimulate ERK or induce cyclin D
      expression. Contrarily, estradiol inhibits serum-dependent retinoblastoma protein
      (Rb) phosphorylation and blocks DNA synthesis. This inhibition does not formally
      arrest cells, and is reversible within hours of estrogen withdrawal. Our data are
      consistent with growth inhibition by activation of Rb and indicate that
      sensitivity to hormone therapy in anticancer treatment can be modulated by cell
      cycle regulators downstream of the estrogen receptor.

PMID- 14580718
TI  - Diurnal variation in p42/44 mitogen-activated protein kinase in the rat pineal
      gland.
AB  - In this study, we investigated whether there was a diurnal difference in mitogen
      activated protein kinase (p42/44(MAPK)) phosphorylation in the rat pineal gland.
      Under a lighting regimen with 12h of darkness, there was a two- to four-fold
      increase in phosphorylated levels of MAPK kinase 1/2 (MEK1/2) and p42/44(MAPK) 2h
      after onset of darkness, an increase that was sustained for 8h. The increases in
      phosphorylated levels of MEK1/2 and p42/44(MAPK) occurred without increases in
      MEK1/2 and p42/44(MAPK) proteins. When rats were treated with propranolol 1h
      before onset of darkness or subjected to continuous light exposure during the
      dark phase, the nocturnal increase in MEK1/2 and p42/44(MAPK) phosphorylation was
      reduced. Acute light exposure during darkness caused a decline in MEK1/2 and
      p42/44(MAPK) phosphorylation within 30 min of light exposure. These results
      indicate the presence of a diurnal difference in MEK1/2 and p42/44(MAPK)
      phosphorylation in the rat pineal gland that is under adrenergic control.

PMID- 14580719
TI  - Pro-apoptotic signals of the bcl-2 gene family in the rat uterus occurs in the
      night before the day of estrus and precedes ovulation.
AB  - Although regression of the endometrium during the rat estrous cycle is a well
      recognized event, little is known concerning the mechanisms involved in
      triggering apoptosis in the rat uterine epithelium. In an attempt to have a
      better understanding of the mechanisms underlying apoptosis during estrus, we
      evaluated the expression of several key apoptotic genes of the bcl-2 family
      during the transition from proestrus to estrus day in the rat. Our results show
      significant changes in the expression of bcl-2 family genes at midnight before
      estrus, characterized by a significant increase in the pro-apoptotic ratios:
      Bax/Bcl-2 and Bcl-xS/Bcl-xL at both mRNA and protein levels. Our results indicate
      the existence of a positive relation between apoptosis and pro-apoptotic ratios
      of bcl-2 gene family expression, during the transition from proestrus to estrus
      day. Importantly, pro-apoptotic signals were detected before ovulation occurred.
      The overall results suggest that the apoptotic process of the rat endometrium
      begins at midnight before the day of estrus, may be mediated by Bcl-2 family
      genes, and precedes ovulation.

PMID- 14580720
TI  - Allelic variation in the hemolymph juvenile hormone binding protein gene of
      Manduca sexta.
AB  - Peripheral distribution of the insect juvenile hormones (JHs) requires hemolymph
      transport proteins. A comparison of three strains of the tobacco hornworm Manduca
      sexta indicates that hemolymph JH binding protein (hJHBP) levels in the Madison
      wild-type (Mwt) strain are significantly higher than in the black larval mutant
      (bl) and Seattle wild-type (Swt) strains. To correlate differences in hJHBP
      levels between strain phenotypes with the hJHBP locus, we sequenced 8.4 kb of the
      hJHBP gene locus from each strain. Snb, an allele found in the Swt and bl
      strains, contains a 408 bp repetitive nuclear element flanked by 15 bp direct
      repeats. Mating studies coupled with molecular genotyping demonstrate that the
      presence of Snb correlates with a twofold lower hJHBP level relative to the
      allele found in the Mwt strain. Despite the lower hJHBP levels in individuals
      carrying the Snb gene, hemolymph levels of JH do not appear to be significantly
      affected.

PMID- 14580721
TI  - The RHL-1 subunit of the asialoglycoprotein receptor of thyroid cells: cellular
      localization and its role in thyroglobulin endocytosis.
AB  - The rat hepatic lectin (RHL)-1 is the major component of the rat liver
      asialoglycoprotein receptor (ASGPr), a membrane receptor highly expressed on the
      basolateral side of hepatocytes, which mediates endocytosis of serum desialated
      glycoproteins. We have recently shown that RHL-1 is expressed in rat thyroid
      tissue and thyroid differentiated cell lines. Both in vitro and in vivo assays
      show that thyrotropin up-regulates thyroid RHL-1 expression, while neoplastic
      transformation of thyroid cells exerts a down-regulation of receptor expression.
      Moreover, RHL-1 expressed on the surface of differentiated thyroid cells is able
      to bind thyroglobulin (Tg), the macromolecular site of synthesis and storage of
      thyroid hormones. In the present work, we demonstrate, by immunohistochemistry
      analysis, that RHL-1 is localized on the apical surface of thyrocytes, at a
      variance with its basolateral localization on hepatocytes. Moreover, albeit its
      expression in thyroid is less abundant than in liver, the receptor is able to
      bind asialorosomucoid (ASOR), the best-known ligand of hepatic ASGPr, and to
      mediate endocytosis of a significative amount of Tg on the surface of
      differentiated PC Cl3 thyroid cells. Taken together, the data suggest that RHL-1,
      even if expressed in thyroid at lower levels than in liver, could serve as a
      receptor for endocytosis of colloidal Tg and, likely, for its delivery to
      lysosomes.

PMID- 14580723
TI  - EMERGY-based environmental systems assessment of a multi-purpose temperate mixed
      forest watershed of the southern Appalachian Mountains, USA.
AB  - Emergy (with an 'm') synthesis was used to assess the balance between nature and
      humanity and the equity among forest outcomes of a US Forest Service ecosystem
      management demonstration project on the Wine Spring Creek watershed, a high
      elevation (1600 m), temperate forest located in the southern Appalachian
      mountains of North Carolina, USA. EM embraces a holistic perspective, accounting
      for the multiple temporal and spatial scales of forest processes and public
      interactions, to balance the ecological, economic, and social demands placed on
      land resources. Emergy synthesis is a modeling tool that allows the structure and
      function of forest ecosystems to be quantified in common units (solar emergy
      joules, sej) for easy and meaningful comparison, determining 'system-value' for
      forcing factors, components, and processes based on the amount of resources
      required to develop and sustain them, whether they are money, material, energy,
      or information. The Environmental Loading Ratio (ELR), the units of solar emergy
      imported into the watershed via human control per unit of indigenous, natural
      solar emergy, was determined to be 0.42, indicating that the load on the natural
      environment was not ecologically damaging and that excess ecological capacity
      existed for increasing non-ecological activities (e.g. timbering, recreation) to
      achieve an ELR of 1.0 (perfect ecological-economic balance). Three forest
      outcomes selected to represent the three categories of desired sustainability
      (ecological, economic, and social) were evaluated in terms of their solar emergy
      flow to measure outcome equity. Direct economic contribution was an order of
      magnitude less (224 x 10(12)solar emergy-joules (sej) ha(-1)) than the ecological
      and social contributions, which were provided at annual rates of 3083 and 2102 x
      10(12)sejha(-1), respectively. Emergy synthesis was demonstrated to holistically
      integrate and quantify the interconnections of a coupled nature-human system
      allowing the goals of ecological balance and outcome equity to be measured
      quantitatively.

PMID- 14580724
TI  - The removal of dyes from textile wastewater: a study of the physical
      characteristics and adsorption mechanisms of diatomaceous earth.
AB  - The feasibility of using diatomite for the removal of the problematic reactive
      dyes as well as basic dyes from textile wastewater was investigated. Methylene
      blue, Cibacron reactive black and reactive yellow dyes were considered. Physical
      characteristics of diatomite such as pHsolution, pHZPC, surface area, Fourier
      transform infrared, and scanning electron microscopy were investigated. The
      surface area of diatomite was found to be 27.80 m2g(-1) and the pHZPC occurred
      around pH of 5.4. The results indicated that the surface charge of diatomite
      decreased as the pH of the solution increased with the maximum methylene blue
      removal from aqueous solution occurring at basic pH of around (10-11). Adsorption
      isotherms of diatomite with methylene blue, hydrolysed reactive black and yellow
      dyes were constructed at different pH values, initial dye concentrations and
      particle sizes. The experimental results were fitted to the Langmuir, Freundlich,
      and Henry models. The study indicated that electrostatic interactions play an
      important role in the adsorption of dyes onto diatomite. A model of the
      adsorption mechanism of methylene blue onto diatomite is proposed.

PMID- 14580722
TI  - WT1 and DAX-1 regulate SF-1-mediated human P450arom gene expression in gonadal
      cells.
AB  - Binding activity of steroidogenic factor-1 (SF-1) to promoters of the majority of
      steroidogenic genes in response to gonadotropins is a critical mechanism that
      regulates steroidogenesis in gonads. Thus, the modulation of SF-1 action may be
      essential for the differential regulation of formation of sex steroids in the
      ovary. Aromatase P450 (P450arom) is the rate-limiting enzyme for estrogen
      formation. In this study, we characterize another nuclear receptor half site in
      the gonadal aromatase promoter which we show to be important for aromatase
      regulation. We also show herein that the stimulation of P450arom promoter
      activity by SF-1 in ovarian granulosa, testicular Sertoli and JEG-3
      choriocarcinoma cells is inhibited by two transcription factors, Wilms' tumor
      suppressor gene (WT1) and dosage sensitive sex reversal adrenal hypoplasia
      congenita critical region on the X chromosome gene 1 (DAX-1). Given the
      characterized roles of these transcription factors in gonadal development and
      function, modulation of SF-1 action by WT1 and DAX-1 may represent an important
      key mechanism in steroidogenesis.

PMID- 14580725
TI  - Water issues in comprehensive municipal planning: a review of the Motala River
      Basin.
AB  - The performance level for water management is rising in Sweden after the passing
      of a number of Governmental Bills (1997-2000) that establish national
      environmental quality objectives, and furthermore after the adoption of the Water
      Framework Directive of the European Union (2000). The presentation of water
      issues in municipal physical planning is important because the municipalities
      have a local planning monopoly. We investigate to what extent water resources are
      considered in one of the most important tools for the regulation of physical
      infrastructure, namely the Comprehensive Municipal Plans. Thirteen plans from
      municipalities within the Motala River Basin in southern Sweden were studied. To
      characterise the comprehensiveness of the plans we used twelve criteria, divided
      into five groups: description, preventive measures, goal-setting, implementation
      strategy and future-oriented considerations. Descriptions of water quality, water
      use, wastewater plants, and urban water and wastewater systems were the most
      frequent items. These topics could be found in all plans in the study, along with
      more or less elaborated river basin perspectives. Issues related to national
      environmental quality objectives were mentioned in only five of the plans, and
      considerations about water flows were even more rare. We found, that the emphasis
      on water issues is not correlated with the size of the municipal population but
      rather with the age of the plans. In the old plans from the early 1990s water
      management is less recognised than in the newly revised ones. After their
      adoption the national water quality objectives, and suggested measures to fulfil
      them, are being translated into regional and local levels, and this has happened
      in the new plans. However, it seems that water has not yet gained the same
      importance as land in municipal physical planning, and strategies for public
      participation in the planning process are lacking.

PMID- 14580726
TI  - Transport of gellan gum microbeads through sand: an experimental evaluation for
      encapsulated cell bioaugmentation.
AB  - Transport of 10-40 microm gellan gum microbeads was studied in horizontal sand
      columns to evaluate the feasibility of using gel-encapsulated bacteria for
      bioaugmentation of contaminated aquifers. Three 5.2 x 110 cm columns were packed
      with sand (column A: 0.5-2 mm, column B: 0.25-2 mm, and column C: 0.125-2 mm).
      Microbeads in artificial groundwater were injected at 0.5 l h(-1) during
      intermittent 12-h periods. Breakthrough of microbeads increased with injection
      time, varying as a descending function of travel distance. After 72 h of
      injection, about 75% of injected microbeads were dispersed across a 5-110 cm
      distance from the inlet in column A, compared to 78% across a 5-50 cm in column
      B, and 76% across a 5-20 cm in column C. The wider dispersion of microbeads
      across the length of column A, compared to those observed in columns B and C,
      suggests a higher potential for the formation of a uniform bioactive zone of
      encapsulated cells across a sandy aquifer with such grain size distribution and
      hydrodynamic properties.

PMID- 14580728
TI  - Applying local knowledge: the contribution of oral history to wetland
      rehabilitation at Kanyapella Basin, Australia.
AB  - Local knowledge of the history and ecology of wetland ecosystems can be a
      valuable resource in wetland rehabilitation projects. This is especially the case
      when other historical ecological information is unavailable. As well as providing
      a source of historical information, time spent acquiring local knowledge can
      enhance public participation in environmental management and facilitate early
      conflict resolution between stakeholders and the community. This paper
      investigates the use of oral history as a tool to collate a history of the
      flooding, ecology and management of Kanyapella Basin, a 2581 ha wetland on the
      floodplain of the Murray and Goulburn Rivers, Australia. Interviews were held
      with nine local residents and 11 natural resource managers. Oral history proved
      an effective way to obtain information about changes in the frequency and
      distribution of flood events over the last 60 years. Observations of rare and
      threatened fauna, and comments regarding the success of past management were also
      recorded. Results from the oral history have been used to direct ecological
      research and develop alternative management options at Kanyapella Basin. In
      addition to its use in gathering ecological information, oral history also proved
      effective in enabling the values and concerns of local community and stakeholders
      to be articulated, increasing managers' understanding of the social context of
      the particular locality, which is fundamental to sound environmental decision
      making.

PMID- 14580727
TI  - Valuing freshwater salmon habitat on the west coast of Canada.
AB  - Changes in land use can potentially reduce the quality of fish habitat and affect
      the economic value of commercial and sport fisheries that rely on the affected
      stocks. Parks and protected areas that restrict land-use activities provide
      benefits, such as ecosystem services, in addition to recreation and preservation
      of wildlife. Placing values on these other benefits of protected areas poses a
      major challenge for land-use planning. In this paper, we present a framework for
      valuing benefits for fisheries from protecting areas from degradation, using the
      example of the Strait of Georgia coho salmon fishery in southern British
      Columbia, Canada. Our study improves upon previous methods used to value fish
      habitat in two major respects. First, we use a bioeconomic model of the coho
      fishery to derive estimates of value that are consistent with economic theory.
      Second, we estimate the value of changing the quality of fish habitat by using
      empirical analyses to link fish population dynamics with indices of land use in
      surrounding watersheds. In our example, we estimated that the value of protecting
      habitat ecosystem services is C$0.93 to C$2.63 per ha of drainage basin or about
      C$1322 to C$7010 per km of salmon stream length (C$1.00=US$0.71). Sensitivity
      analyses suggest that these values are relatively robust to different
      assumptions, and if anything, are likely to be minimum estimates. Thus, when
      comparing alternative uses of land, managers should consider ecosystem services
      from maintaining habitat for productive fish populations along with other
      benefits of protected areas.

PMID- 14580729
TI  - Biosorption of copper (II) from chemical mechanical planarization wastewaters.
AB  - Copper Chemical Mechanical Planarization (Cu-CMP) is a critical step in
      integrated circuit (IC) device manufacturing. CMP and post-CMP cleaning processes
      are projected to account for 30-40% of the water consumed by IC manufacturers in
      2003. CMP wastewater is expected to contain increasing amounts of copper as the
      industry switches from Al-CMP to Cu-CMP causing some IC manufacturers to run the
      risk of violating discharge regulations. There are a variety of treatment schemes
      currently available for the removal of heavy metals from CMP wastewater, however,
      many introduce additional chemicals to the wastewater, have large space
      requirements, or are expensive. This work explores the use of microorganisms for
      waste treatment. A Staphylococcus sp. of bacteria was isolated and studied to
      determine the feasibility for use in removing copper from Cu-CMP wastewater. A
      model Cu-CMP wastewater was developed and tested, as well as actual Cu-CMP
      wastes. Continuous-flow packed column experiments were performed to obtain
      adsorption data and show copper recovery from the waste. A predictive, empirical
      model was used to accurately describe Cu removal. Additionally, the immobilized
      cells were regenerated, allowing for the concentration and potential recovery of
      copper from the wastewater.

PMID- 14580730
TI  - Impacts of nutrient additions and digging for human waste disposal in natural
      environments, Tasmania, Australia.
AB  - Very little research has been undertaken on the impacts of human toilet waste
      disposal in non-serviced sites in the wild. The objective of the present project
      was to determine the relative impacts of the mechanical disturbance of digging
      during the burial of toilet waste (faeces and toilet paper), and urination, on
      Tasmanian vegetation types that occur in areas used for wild country camping, in
      order to develop appropriate guidelines. The mechanical disturbance of digging
      cat-holes 15 cm deep, typical of those used for toilet disposal in the Tasmanian
      wild, had largely negative effects on the growth of a few native plant species.
      These effects were of little or no conservation significance. The nutrient
      additions simulated by the addition of artificial urine to undug ground and dug
      ground had largely positive effects on nine distinct types of native vegetation,
      encouraging the growth of many plant species at many sites, while discouraging
      the growth of moss at one site. No weed species found at any of the sites were
      significantly affected by the treatments. Thus, it appears that scattered
      disposal of urine, even combined with digging, is unlikely to present a major
      conservation problem in the Tasmania's wild country, and that present guidelines
      are appropriate, where achievable.

PMID- 14580731
TI  - Lessons from community based management of floodplain fisheries in Bangladesh.
AB  - Inland (floodplain) fisheries remain the most important contributor to fish
      production in Bangladesh. They have in the past been administered to generate
      government revenue without due concern for sustainability or equity. Community
      Based Fisheries Management (CBFM) is a possible solution and was tested in 19
      waterbodies (rivers and beels) during 1996-2000. The outcomes so far are assessed
      with respect to social, institutional, and physical context, and the interactions
      that arose in establishing CBFM. The lessons drawn are that: it was essential
      that communities obtained rights over the fisheries, strong facilitation was
      necessary, taking up visible resource management actions greatly helped, success
      was more likely in homogeneous communities, external threats were a strong
      limiting factor, clear boundaries and small fisheries were not so critical, and
      new institutions could be built with as much ease (or difficulty) as modifying
      existing ones. Effective well-defined partnerships of NGOs and government were
      not easy to establish but were sufficiently beneficial that in several locations
      new community institutions for fisheries management were established. This is a
      slow process, the sustainability of local management institutions is not yet
      established, although they continued during an interim period without funding,
      further phased support is planned to strengthen these organizations and to
      generate evidence of impacts and momentum to influence wider fisheries policy in
      and beyond Bangladesh.

PMID- 14580733
TI  - Education in resuscitation.

PMID- 14580734
TI  - Recommended guidelines for uniform reporting of data from drowning: the "Utstein
      style".

PMID- 14580735
TI  - Do clinically relevant transthoracic defibrillation energies cause myocardial
      damage and dysfunction?
AB  - Sufficiently strong defibrillation shocks will cause temporary or permanent
      damage to the heart. Weak defibrillation shocks do not cause any damage to the
      heart but also do not defibrillate. A relevant and practical question is what
      range of shock energies is most likely to defibrillate while not causing damage
      to the heart. This question is most difficult to answer in the pre-hospital
      defibrillation setting where the patients' size and shape vary, placement of the
      defibrillation patches vary, and the etiology of their arrhythmia varies. Unlike
      internal defibrillators, which are tested at implantation, efficacy of an
      external defibrillator is determined only once, when it is most needed. This
      review discusses shock damage and dysfunction caused by monophasic waveforms as
      well as biphasic waveforms. Evidence is presented suggesting that for perfused
      hearts, the threshold for damage is well above any shock size delivered
      clinically. For non-perfused hearts, both in humans and animals, evidence is
      presented that monophasic shocks of up to 5 J/kg do not cause any more cardiac
      damage/dysfunction than that associated with smaller shocks and that much of this
      damage is caused by the ischemic period itself rather than the shock. Although
      many patients can be defibrillated with 150 J (2.2 J/kg) biphasic shocks, some
      patients may require biphasic shocks up to 360 J (5 J/kg) to be defibrillated.
      Studies still need to be performed comparing the efficacy and damaging effects of
      360 J biphasic shocks to 150 J biphasic shocks. Until those studies are
      completed, it seems reasonable to use the same 360 J (5 J/kg) energy limit for
      biphasic shocks as for monophasic shocks.

PMID- 14580736
TI  - Interposed abdominal compression CPR: a comprehensive evidence based review.
AB  - Interposed abdominal compression (IAC)-CPR includes all steps of standard
      external CPR with the addition of manual mid-abdominal compressions in
      counterpoint to the rhythm of chest compressions. IAC-CPR can increase blood flow
      during CPR about 2-fold compared with standard CPR without IAC, as shown by six
      of six studies in computer models and 19 of 20 studies in various animal models.
      The addition of IAC has clinical benefit in humans, as indicated in 10 of 12
      small to medium sized clinical studies. The technique increases the frequency of
      immediate return of spontaneous circulation for in-hospital resuscitations from
      roughly 25 to 50%. Improved survival to discharge is also likely on the basis of
      two small in-hospital trials. Possible harm from abdominal compression is minimal
      on the basis of 426 humans, 151 dogs and 14 pigs that received IAC in published
      reports. The complexity of performing IAC is similar to that of opening the
      airway and is less than that of other basic life support maneuvers. The aggregate
      evidence suggests that IAC-CPR is a safe and effective means to increase organ
      perfusion and survival, when performed by professionally trained responders in a
      hospital and when initiated early in the resuscitation protocol. Cost and
      logistical considerations discourage use of IAC-CPR outside of hospitals.

PMID- 14580737
TI  - What is the optimal paddle force during paediatric external defibrillation?
AB  - INTRODUCTION: Transthoracic impedance (TTI) is a major determinant of
      transmyocardial current flow, and therefore, the success of defibrillation.
      European Resuscitation Council (ERC) paediatric guidelines recommend that 'firm'
      paddle force should be applied to the paddles during defibrillation. No study has
      yet established the optimal paddle force required to minimise TTI in children of
      different ages. METHODS: Eighty patients aged 10 weeks to 17 yrs undergoing
      general anaesthesia for routine surgery were studied. Using defibrillation
      paddles placed in an anterior-apical position, TTI (Omega) was measured for
      increasing values of force from 0.5 kgf (baseline) to 6.5 kgf. The optimal force,
      the force to achieve 95% of the overall reduction in TTI, was then determined.
      According to current guidelines, paediatric paddles (surface area 16 cm2) were
      used for infants (< or =10 kg) and adult paddles (82 cm2) for older children.
      Optimal force was then calculated for infants < or =10 kg, children >10 kg and <
      or =8 yrs and children 9-17 yrs age. RESULTS: Increasing paddle force from 0.5
      kgf progressively decreased TTI. Optimal force using paediatric paddles was 2.9
      kgf in infants. Optimal force using adult paddles was 5.1 kgf in children >10 kg
      but < or = 8 yrs and 5.3 kgf in children aged 9-17 yrs. CONCLUSIONS: Force is an
      important determinant of TTI and therefore, outcome of defibrillation. It is
      recommended that a minimum of 3 kgf be applied to paddles when defibrillating
      infants with paediatric paddles, and a minimum of 5 kgf be applied to all older
      children when adult paddles are used.

PMID- 14580738
TI  - Pre-printed 'do not attempt resuscitation' forms improve documentation?
AB  - OBJECTIVE: Do not-attempt-resuscitate orders are fundamental for allowing
      patients to die peacefully without inappropriate resuscitation attempts. Once the
      decision has been made it is imperative to record this information accurately.
      However, during a related research projected we noted that documentation was poor
      and we thought that the introduction of a pre-printed Do Not Attempt
      Resuscitation (DNAR) form would improve the documentation process. DESIGN: Two
      sets of identical research questions were applied retrospectively, 12-months
      apart, to notes of adult patients (>18 years) who had died during a hospital
      admission without under-going a resuscitation attempt. Between the first and the
      second audit, a new resuscitation policy that incorporated a pre-printed DNAR
      form was introduced into our hospital. RESULTS: A pre-printed DNAR form improved
      documentation when measured against; clarity of DNAR order (P=0.05), date
      decision was made/implementation (P=0.014), presence of clinician's signature
      (P=0.001), identification of the senior clinician making the decision (P< or
      =0.001) and justification for the DNAR decision (P< or =0.001). However, the pre
      printed form made little improvement in encouraging patient involvement in the
      DNAR decision-making process (P=0.348). CONCLUSION: A pre-printed DNAR form can
      improve documentation significantly but it has little effect in encouraging
      patient involvement in the decision-making process.

PMID- 14580739
TI  - Cardiac arrest survival as a function of ambulance deployment strategy in a large
      urban emergency medical services system.
AB  - INTRODUCTION: This study examines the effect of paramedic deployment strategy on
      witnessed ventricular fibrillation (VF) cardiac arrest outcomes. Our null
      hypothesis was that there is no difference in survival between an EMS system
      using targeted response (TR) and one using a uniform or all advanced life support
      (ALS) response (UR) model. We define targeted response as a system where
      paramedics are sent to critical incidents while ambulances staffed with basic
      EMTs are sent to less critical incidents. A secondary outcome measure was
      paramedic skill proficiency between the systems. METHODS: We conducted a
      retrospective review of all 1997 VF arrests in a large urban EMS system. The
      majority of the city is a busy, urban area that uses TR. Outlying areas of the
      city are suburban and are served by a UR model. All areas have first responders
      equipped with automated external defibrillators. Outcomes are compared using
      Utstein criteria. RESULTS: Patient populations were well matched. There were 181
      patients in the TR group and 24 in the UR group. Units in the TR area were able
      to demonstrate shorter response and time to defibrillation intervals than in the
      UR area. Rates for return of spontaneous circulation (ROSC), admission to the
      ward/intensive care unit (ICU), survival to discharge and survival to 1 year were
      all better in the cohort of patients cared for in the TR area than those in the
      UR area. Rates for successful intubation and IV initiation were also better in
      the TR areas than in the UR areas. CONCLUSION: This study shows improved outcomes
      for a subset of patients with cardiac arrest when they are cared for in an area
      that uses TR compared to an area that uses a UR EMS system.

PMID- 14580740
TI  - Procalcitonin serum levels after out-of-hospital cardiac arrest.
AB  - The time course of Procalcitonin (PCT) serum levels was assessed in cardiac
      arrest survivors and compared with S-100 serum levels concerning their predictive
      values for neurological outcome. PCT and S-100 serum levels were analyzed
      serially on admission and during the following 3 days after hospitalization in 23
      patients successfully resuscitated from out-of-hospital cardiac arrest. At day 14
      patients were divided into groups according to the Glasgow-Outcome-Scale (GOS):
      one group with bad neurological outcome (GOS 1-3) and one group with good
      neurological outcome (GOS 4-5). Group comparisons were performed with the Mann
      Whitney U-Test. The diagnostic performance of PCT and S-100 levels was analyzed
      using receiver operating characteristics (ROC). Patients with a bad neurological
      outcome had significantly higher S-100 levels than those with a good neurological
      outcome at all investigated time points and significantly elevated PCT levels at
      days 1-3. Highest levels for S-100 were found immediately after hospitalization
      (3.4 +/- 3.8 vs. 0.7 +/- 0.3 microg/l, P=0.003), and for PCT at day 1 (37 +/- 103
      vs. 0.2 +/- 0.2 microg/l, P=0.0002). The results show that PCT serum levels are
      possibly elevated in patients with bad neurological outcome after cardiac arrest,
      without signs of severe infection or concomitant sepsis. Based on this
      observation, studies on larger numbers of patients should prove the predictive
      value of PCT in those patients.

PMID- 14580741
TI  - Management of ventricular fibrillation or unstable ventricular tachycardia in
      patients with congenital long-QT syndrome: a suggested modification to ACLS
      guidelines.
AB  - Prolongation of the QT interval is a known risk factor for syncope, seizures and
      sudden cardiac death. Most patients with QT prolongation have an acquired cause,
      but congenital forms of QT prolongation are being increasingly recognized.
      However, existing advanced cardiac life support (ACLS) treatment algorithms for
      prolonged QT mediated ventricular fibrillation pertains to acquired long-QT
      syndrome (LQTS). Here, a young patient with out-of-hospital cardiac arrest
      secondary to congenital LQTS illustrates critical exceptions to the current ACLS
      treatment algorithms for ventricular fibrillation and unstable ventricular
      tachycardia when QT prolongation is congenital in origin. A clarified ACLS
      algorithm is proposed.

PMID- 14580742
TI  - Endobronchial adrenaline: should it be reconsidered? Dose response and
      haemodynamic effect in dogs.
AB  - BACKGROUND: Tracheal drug administration is a route for drug delivery during
      cardiopulmonary resuscitation when intravenous access is not immediately
      available. However, tracheal adrenaline (epinephrine) injection has been recently
      shown to be associated with detrimental decrease in blood pressure. This was
      attributed to exaggerated early beta2 mediated effects unopposed by alpha
      adrenergic vasoconstriction. We hypothesized that endobronchial adrenaline
      administration is associated with better drug absorption, which may abolish the
      deleterious drop of blood pressure associated with tracheal drug administration.
      OBJECTIVE: To determine haemodynamic variables after endobronchial adrenaline
      administration in a non-arrest canine model. DESIGN: Prospective, randomized,
      laboratory study. METHODS: Adrenaline (0.02, 0.05, 0.1 mg/kg) diluted with normal
      saline was injected into the bronchial tree of five anaesthetized dogs. Injection
      of 10-ml saline served as control. Heart rate, blood pressure and arterial blood
      gases were monitored for 60 min after drug instillation. The protocol was
      repeated after 1 week. RESULTS: Adrenaline at a dose of 0.02 mg/kg produced only
      a minor initial decrease in diastolic (from 90 +/- 5 to 78 +/- 3 mmHg, P=0.05),
      and mean blood pressure (from 107 +/- 4 to 100 +/- 3 mmHg, P=0.05), in all dogs.
      This effect lasted less then 30 s following the drug administration. In contrast,
      higher adrenaline doses (0.05 and 0.1 mg/kg) produced an immediate increase in
      diastolic (from 90 +/- 5 to 120 +/- 7 mmHg; and from 90 +/- 5 to 170 +/- 6 mmHg,
      respectively), and mean blood pressure (from 107 +/- 4 to 155 +/- 10 mmHg; and
      from 107 +/- 4 to 219 +/- 6 mmHg, respectively). All adrenaline doses resulted in
      an immediate increase in systolic blood pressure and pulse. Endobronchial
      administration of saline (control) affected none of the haemodynamic variables.
      CONCLUSIONS: In a non-arrest model, endobronchial adrenaline administration, as
      opposed to the effect of tracheal adrenaline, produced only a minor decrease in
      diastolic and mean blood pressure. We suggest that endobronchial adrenaline
      administration should be investigated further in a CPR low-flow model when
      maintaining adequate diastolic pressure may be crucial for survival.

PMID- 14580743
TI  - To blow or not to blow: a randomised controlled trial of compression-only and
      standard telephone CPR instructions in simulated cardiac arrest.
AB  - This randomised controlled trial used a manikin model of cardiac arrest to
      compare skill performance in untrained lay persons randomised to receive either
      compression-only telephone CPR (Compression-only tel., n=29) or standard
      telephone CPR instructions (Standard tel., n=30). Performance was evaluated
      during standardised 10 min cardiac arrest simulations using a video recording and
      data from a laptop computer connected to the training manikin. A number of
      subjects in both groups did not open the airway. More than 75% in the Standard
      tel. group failed to deliver two effective initial rescue breaths, and only 17%
      provided an adequate inflation volume for subsequent breaths, delivering a median
      of only five inflations during the entire scenario. Most subjects in both groups
      gave chest compressions that were too shallow and at an inappropriately rapid
      rate. Hand position was also poor, but was worse in the group given simplified
      instructions. There was a significant delay to first compression in both groups,
      although this interval was shortened by over a minute when ventilations were
      eliminated from the telephone instruction algorithm (245 vs. 184 s, P<0.001).
      Over two-and-a-half times as many chest compressions were delivered during an
      average ambulance response time with compression-only telephone directions
      compared with standard CPR (461 vs. 186, P<0.001). These variables may be
      critical in predicting survival from out-of-hospital cardiac arrest. Further
      research is necessary to establish if modifications to scripted telephone
      instructions can remedy the identified performance deficiencies. Eliminating
      instructions for rescue breaths from scripted telephone directions will have
      little impact on the ventilation of most patients. Research is required to
      determine if the consequent reduction in the delay to starting chest compressions
      and the significant increase in the number of compressions delivered can increase
      survival from out-of-hospital cardiac arrest.

PMID- 14580744
TI  - Utilization of virtual reality for endotracheal intubation training.
AB  - Tracheal intubation is performed for urgent airway control in injured patients.
      Current methods of training include working on cadavers and manikins, which lack
      the realism of a living human being. Work in this field has been limited due to
      the complex nature of simulating in real-time, the interactive forces and
      deformations which occur during an actual patient intubation. This study
      addressed the issue of intubation training in an attempt to bridge the gap
      between actual and virtual patient scenarios. The haptic device along with the
      real-time performance of the simulator give it both visual and physical realism.
      The three-dimensional viewing and interaction available through virtual reality
      make it possible for physicians, pre-hospital personnel and students to practice
      many endotracheal intubations without ever touching a patient. The ability for a
      medical professional to practice a procedure multiple times prior to performing
      it on a patient will both enhance the skill of the individual while reducing the
      risk to the patient.

PMID- 14580745
TI  - Calcitonin gene-related peptide protects against whole body ischemia in a porcine
      model of cardiopulmonary resuscitation.
AB  - The present study was designed to investigate the protective effects of
      calcitonin gene-related peptide (CGRP) in a porcine model of cardiopulmonary
      resuscitation (CPR). Twelve pigs were anesthetized, paralyzed, mechanically
      ventilated with oxygen, and were monitored for electrocardiograph (ECG), arterial
      pressure, right atrial pressure, airway pressure. Ventricular fibrillation (VF)
      was induced in all animals by the application of 30 V of alternating current (60
      Hz) across the heart, and remained untreated for 3 min, followed by conventional
      CPR with pneumatic piston device (Thumper) for 15 min. At 18 min of VF a single
      dose of vasopressin was given, and followed by defibrillation attempts. Two
      groups were studied. Group 1: Six pigs were used as saline control. Group 2: 0.3
      nmol/kg CGRP was given 15 min prior to induction of VF. All animals in the CGRP
      pretreated group achieved a return of spontaneous circulation (ROSC) and survived
      more than 2 h (100%), whereas none of the saline control animals achieved ROSC.
      Blood gases were not significantly different between the groups. However, CGRP
      group had significantly higher arterial blood pressure and coronary perfusion
      pressure than control group during CPR. Pretreatment with CGRP affords a
      cardioprotective effect in this model of whole body ischemia.

PMID- 14580746
TI  - Basilar artery thrombosis in a trauma patient. Case report and review of the
      literature.
AB  - Thrombotic disease of the vertebrobasilar circulation is associated with a poor
      prognosis. It may occur in trauma patients, especially those with neck injuries
      and even several months after the initial insult. We report on the case of a
      young polytrauma patient, victim of a traffic accident, with associated cervical
      and thoracic spinal injuries resulting in paraplegia. Consciousness was not
      impaired initially, but during transfer to our hospital he became suddenly
      unconscious. An occluded basilar artery was found on angiography, but
      unfortunately we were unable to reopen the vessel with thrombolytic therapy. This
      case again proves that lesions of the vertebro-basilar system must always be
      suspected in neck injuries. Even after minor whiplash injuries, fatal basilar
      thrombosis may occur. A review of all reported cases of traumatic basilar artery
      thrombosis is given and the use of thrombolytic therapy is discussed.

PMID- 14580748
TI  - The effect of antenatal corticosteroids on gut peptides of preterm infants--a
      matched group comparison: corticosteroids and gut development.
AB  - BACKGROUND: Postnatal glucocorticosteroid administration has trophic effects on
      the gastrointestinal tract of preterm infants. The aim of the present study was
      to investigate whether antenatal glucocorticosteroids affect the secretion of
      gastrointestinal peptides that are involved in the regulation of secretion,
      motility and mucosal protection of the gastrointestinal tract. METHODS: Plasma
      levels of gastrin, motilin and vasoactive intestinal peptide (VIP) were estimated
      in 28 preterm infants with a mean birth weight of 1280 g, and mean gestational
      age of 30.5 weeks, whose mothers had received a full course of antenatal
      glucocorticosteroids (GC group) and in 17 preterm infants with mean birth weight
      of 1200 g, mean gestational age of 30.2 weeks, whose mothers had not received
      corticosteroids (control group). GI peptides were estimated on two occasions: (a)
      Immediately after birth and (b) following the initiation of enteral feeding.
      RESULTS: Gastrin levels in the GC group were significantly higher both
      immediately after birth (early measurement) and also after receiving enteral
      feeding (late measurement) (p<0.001, p<0.05, respectively) but the increase in
      plasma gastrin concentration was identical in both groups (32 vs. 33 pg/ml).
      Motilin levels in the GC group were also significantly higher as compared to the
      control group but only in the late measurement (p<0.001). Gastrin and motilin
      levels in both groups were significantly higher in the late measurement as
      compared to the early measurement (GC group: p<0.001, p<0.001, respectively;
      CONTROLS: p<0.001, p<0.01, respectively). There was no significant difference in
      VIP levels between the two groups both in the early and the late measurements.
      CONCLUSION: Antenatal glucocorticoids (GCs) stimulate gastrin secretion in the
      fetus but not in the neonate. Contrary to this, corticosteroid effect on motilin
      is seen only postnatally following the introduction of enteral feeding.
      Glucocorticosteroids appear to have no effect on VIP levels. Plasma gastrin and
      motilin levels increase significantly following the introduction of enteral
      feeding regardless of the use of steroids.

PMID- 14580749
TI  - Enteral feeding of premature infants with Saccharomyces boulardii.
AB  - BACKGROUND: Saccharomyces boulardii (SB) is a yeast that acts both as a probiotic
      and as a polyamine producer. Probiotics prevent the overgrowth of pathogens in
      the gut while polyamines enhance intestinal maturation. The aim of this
      randomized study was to investigate the ability of SB to modify the gut microbial
      ecology and its function. METHODS: A total of 87 healthy babies with gestational
      age 28-32 weeks were studied. They were randomly assigned to receive a preterm
      formula to which SB or maltodextrins was added for 30 days. Evaluations were made
      on the following: SB tolerance and weight gain, faecal flora analysis, intestinal
      D-xylose absorption and faecal lipid excretion. RESULTS: SB was well tolerated by
      the infants. There was no difference in weight gain between the two groups.
      Median log of colony forming units per gram of faeces for Escherichia coli and
      enterococci was significantly lower in the SB group [E. coli: 2.67 (0.045) vs.
      2.75 (0.058), P<0.001; enterococci: 2.14 (0.359) vs. 2.19 (0.138), P<0.05]. On
      the other hand, the number of bifidobacteria and staphylococci in the stools was
      significantly higher in the SB group [bifidobacteria: 2.65 (0.083) vs. 2.27
      (0.075), P<0.001; staphylococci: 1.23 (0.869) vs. 0.6 (0.281), P<0.001]. D-Xylose
      and lipid absorption was not improved by SB [median blood D-xylose: 1.5 (0.4)
      mmol/l vs. 1.35 (0.3) mmol/l, P>0.1; median stool steatocrit: 64% (3.05%) vs. 65%
      (2.72%) P>0.5]. CONCLUSIONS: An SB-supplemented formula is well tolerated by
      preterm infants, it has a beneficial effect on stool flora bringing it closer to
      that of breast fed babies but it does not improve D-xylose or lipid gut
      absorption.

PMID- 14580750
TI  - Psychomotor development and general movements in offspring of women with epilepsy
      and anticonvulsant therapy.
AB  - While the role of antiepileptic drug (AED) therapy in teratogenesis has widely
      been investigated, there are few prospective studies on later postnatal
      development in offspring of epileptic women in utero exposed. The aim of this
      study was a prospective investigation of the psychomotor development in a
      selected population of infant born to women with epilepsy on AED therapy during
      pregnancy. PATIENTS AND METHODS: Children were assessed at various times until 30
      months of age by general movement (GMs) observation (at 7 days and 4 and 13
      weeks), traditional neurologic examination (at 7 days and 4 and 13 weeks, 6, 9
      and 12 months) and Brunet-Lezine (B-L) administration (at 30 months). We present
      the preliminary results of our study conducted on 11 children. RESULTS:
      Psychomotor delay in children was confirmed by traditional neurological
      examinations scores at 7 days, 4 weeks, 13 weeks and 6 months and by B-L score at
      30 months. Between 9 and 12 months of age, traditional neurologic examination
      became "silent". GM assessment was found to be a better predictor of psychomotor
      development. In fact, GM analysis, particularly at 4 weeks, was strongly
      correlated with the Brunet-Lezine score at 30 months. In conclusion, on the basis
      of these data we suggest a psychomotor delay in the offspring of epileptic women
      and that GMs and neurologic evaluation provide complementary information
      concerning psychomotor development and later outcome of these children.

PMID- 14580751
TI  - The development of jejunum and ileum during the fetal period.
AB  - OBJECTIVE: In our study, the morphologic structures of the jejunum and ileum
      sections of small intestine were investigated in human fetuses during the fetal
      period. MATERIALS AND METHODS: The study was realised on 131 human fetuses (male:
      69; female: 62) with ages between 10 and 40 weeks, which have got no external
      pathology and anomalies. The external sizes of fetuses were measured, and then
      the structures in the abdominal cavity were determined by the abdominal
      dissection. The localization of jejunum and ileum, duodenojejunal flexure and
      ileal orifice points, the measurements of macroscopic diameters, types of the
      mass of jejunum and ileum and the localization according to the abdominal regions
      of the mass of jejunum and ileum were determined. Also, the samples of the
      jejunum and ileum were examined both macroscopically and microscopically. The
      thickness of tunica serosa, tunica muscularis and tunica mucosa was determined
      under the light microscope. RESULTS: According to the sexes, gestational ages and
      groups, the averages and the standard deviations of the all parameters were
      determined. The correlations between the parameters were determined. The
      percentage of parameters was compared according to sex and among groups. No
      differences were found in parameters between sexes (p<0.05). The macroscopic
      parameters were increased according to the gestational age. The thickness of
      tunica serosa did not change according to the gestational age. CONCLUSION: It is
      thought that the data we have will help the evaluation of jejunum and ileum in
      intrauterine period; we also believe that the data in our study may help in the
      diagnosis and treatment of anomalies and pathologies in fetal period that belongs
      to jejunum and ileum.

PMID- 14580752
TI  - Fetal response to induced maternal stress.
AB  - BACKGROUND: Despite increased attention to the role of antenatal maternal
      psychological stress in postnatal development, remarkably little information is
      available on the nature of the intrauterine fetal response to maternal
      psychological state. AIMS: To determine whether: (1) the fetus responds to
      maternal stress; (2) the fetal response changes over gestation; and (3)
      individual maternal and fetal response patterns are stable over time. STUDY
      DESIGN: Induced maternal stress at 24 and 36 weeks gestational age using the
      Stroop color-word task. SUBJECTS: 137 low-risk pregnant women with normally
      developing fetuses. OUTCOME MEASURES: Maternal (heart rate and skin conductance)
      and fetal (heart rate, heart rate variability, and motor activity) responses.
      RESULTS: The manipulation evoked maternal sympathetic activation, which declined
      in magnitude from 24 to 36 weeks gestation. Fetuses responded to the manipulation
      with increased variability in heart rate (F(2,256)=7.80, p<0.001) and suppression
      of motor activity (F(2,216)=15.47, p<0.001). The magnitude of the fetal response
      increased over gestation. The degree of maternal reactivity to and recovery from
      the stressor were correlated over time (r's=0.53 and 0.60 for heart rate;
      r's=0.31 and 0.36 for skin conductance; p's<0.001). There was moderate stability
      in the magnitude of the fetal motor response (r=0.25, p<0.01). CONCLUSIONS:
      Demonstration of fetal responses to maternal sympathetic activation evoked by a
      benign cognitive stressor suggests that fetal neurobehavioral regulation is
      routinely disrupted by maternal environmental intrusions. There is no evidence of
      a protective effect of diminished maternal sensitivity to stress on the fetus.
      Individual stability in the magnitude of the evoked maternal physiologic and
      psychological responses from 24 to 36 weeks and stability in the fetal motor
      response implies that characteristic response patterns emerge in utero. We
      propose that autonomic development is partially entrained through these
      processes.

PMID- 14580754
TI  - Insulin regulation of mitochondrial proteins and oxidative phosphorylation in
      human muscle.
AB  - Relationships between insulin action and oxidative capacity in skeletal muscle
      have been suggested in humans, particularly in insulin-resistance-related
      metabolic disorders, such as obesity and diabetes. The regulatory action of
      insulin on fuel metabolism in insulin-sensitive tissues such as skeletal muscle
      is well documented, but the effect of insulin on muscle mitochondrial functions
      and oxidative capacity have yet to be defined in humans. In a recent article,
      Stump et al. investigated the stimulatory action of insulin on mitochondrial
      activities in key cellular events, such as ATP production, enzyme activity,
      mitochondrial protein synthesis, and mRNA expression of transcripts encoding
      mitochondrial proteins. To analyze the impact of insulin resistance on
      mitochondria, Stump et al. conducted their study in subjects with type 2 diabetes
      mellitus and in non-diabetic matched controls. Their results reveal that as well
      as being the predominant postprandial anabolic hormone for substrate utilization,
      insulin is also a major regulating factor of mitochondrial oxidative
      phosphorylation in human skeletal muscle.

PMID- 14580753
TI  - Prenatal maternal cortisol levels and infant behavior during the first 5 months.
AB  - BACKGROUND AND AIMS: Research on both animals and humans is providing more and
      more evidence that prenatal factors can have long-term effects on development.
      Most human studies have examined the effects of prenatal stress on birth outcome
      (i.e. shorter pregnancies, smaller infants). The few studies that have looked at
      the infants' later development have found prenatal stress to be related to more
      difficult temperament, behavioral/emotional problems and poorer motor/cognitive
      development. In this paper, we have examined links between late pregnancy
      cortisol levels and infant behavior during the first 5 months of life. STUDY
      DESIGN AND SUBJECTS: Seventeen mothers and their healthy, full-term infants
      participated in this prospective, longitudinal study. The mothers' cortisol was
      determined in late pregnancy. The infants' behavior was videotaped during a
      series of bath sessions at the home: at 1, 3, 5, 7, 18 and 20 weeks of age. The
      mothers filled in temperament questionnaires (ICQ) in postnatal weeks 7 and 18.
      RESULTS AND CONCLUSIONS: The infants were divided into two groups based on their
      mothers' late pregnancy cortisol values: high and low prenatal cortisol groups. A
      trend was found for the high cortisol infants to be delivered earlier than the
      low cortisol group. Furthermore, the behavioral observations showed the higher
      prenatal cortisol group to display more crying, fussing and negative facial
      expressions. Supporting these findings, maternal reports on temperament also
      showed these infants to have more difficult behavior: they had higher scores on
      emotion and activity. The differences between the infants were strongest at the
      youngest ages (weeks 1-7).

PMID- 14580755
TI  - Fast glucocorticoid feedback favors 'the munchies'.
AB  - In a recent paper, Tasker and colleagues show that glucocorticoids (GCs) act
      rapidly, probably through membrane receptors, on corticotropin-releasing factor
      (CRF)-synthesizing cells to release endocannabinoids. These act locally at
      presynaptic axons via cannabinoid CB-1 receptors to reduce excitatory
      glutaminergic input, and therefore induce fast feedback inhibition of CRF by GCs.
      Similar findings in other hypothalamic neurons suggest that this action of GCs
      might be common in the brain, and could, in part, explain rapid GC effects on
      food intake.

PMID- 14580759
TI  - Genetics of adrenocortical tumors: gatekeepers, landscapers and conductors in
      symphony.
AB  - The genetic and histopathological backgrounds of adrenocortical tumorigenesis
      remain poorly characterized. In other tissues, there is conclusive evidence that
      hyperplasia and adenomas precede cancer. In the adrenal, there are few clinical
      cases of either hyperplasia or adenoma associated with later development of
      cancer, and there are few biological studies that attempt to characterize this
      process molecularly. Current research focuses on the early lesions of the adrenal
      cortex because of their possible molecular link with carcinogenesis, and evidence
      of their frequent association with atypical forms of Cushing's and Conn's
      syndromes, obesity, hypertension and/or diabetes. These studies indicate a model
      for oncogenesis that is the same as that in other tissues. The rarity of adrenal
      cancer compared to benign lesions could be a clue to unique features of
      adrenocortical cells. It might also highlight the function of genes that are
      associated with endocrine tumors in the context of which the concept of gene
      'conductors' is introduced here.

PMID- 14580758
TI  - Lipid overload and overflow: metabolic trauma and the metabolic syndrome.
AB  - Approximately two-thirds of the US population are overweight, which means that
      insulin resistance is probably the most common metabolic abnormality in the USA.
      I propose three novel concepts concerning the causes and consequences of insulin
      resistance that challenge current thinking. First, there is the evidence that
      resistance to insulin-stimulated glucose metabolism is not a primary event in
      obesity, but is secondary to lipid accumulation resulting from full
      responsiveness to insulin-stimulated lipogenic activity. Second, resistance to
      insulin-stimulated glucose metabolism, now considered detrimental to health,
      might be a protective mechanism that reduces lipid-induced damage to tissue by
      excluding glucose from cells, thus decreasing glucose-derived lipogenesis. Third,
      I suggest that lipid-induced insulin resistance and the accompanying metabolic
      syndrome are secondary to leptin resistance, resulting in breakdown in the normal
      partitioning of surplus lipids in the adipocyte compartment.

PMID- 14580760
TI  - Natriuretic peptides: markers or modulators of cardiac hypertrophy?
AB  - The natriuretic peptides (NPs), through their diuretic, vasodilatory and anti
      mitogenic properties, play an important role in the regulation of cardiovascular,
      renal and endocrine homeostasis. Recent studies suggest that they have utility in
      both the diagnosis and management of heart failure. Plasma brain NP (BNP) levels
      have been used to establish prognosis in patients with heart failure and those at
      risk for heart failure post-myocardial infarction. They have been used to
      establish a cardiac etiology for acute shortness of breath, and to guide and
      assess the efficacy of therapy in patients with established heart failure. BNP is
      also approved for use in the management of acute decompensated heart failure. Of
      note, recent studies suggest that cardiac NPs suppress myocyte hypertrophy and
      interstitial fibrosis in the heart, arguing for an important autocrine-paracrine
      role of these peptides in controlling the cardiac response during hypertrophy.
      Therefore, the existing evidence supports a role for BNP as both a marker and a
      modulator of hypertrophy.

PMID- 14580761
TI  - Primary hyperparathyroidism: controversies in surgical management.
AB  - Controversy surrounds the optimal management of patients with mild or
      asymptomatic primary hyperparathyroidism (PHPT). Although many new medical
      therapies for this disorder have emerged in the past decade, existing evidence
      indicates that parathyroidectomy is the only curative option and reverses not
      only many of the classic, but also the more subtle, manifestations of PHPT.
      Moreover, parathyroidectomy can be performed successfully with minimal morbidity
      by experienced surgeons. With the recent development and widespread use of
      several preoperative localization studies, various focused approaches to neck
      exploration and intraoperative parathyroid hormone testing, management for this
      disorder will need to be tailored to individual patients.

PMID- 14580763
TI  - Activation of G-protein-coupled receptors: a common molecular mechanism.
AB  - G-protein-coupled receptors (GPCRs) are a large family of proteins that contain a
      seven transmembrane helical structural motif. They mediate responses to several
      ligands by binding and activating intracellular heterotrimeric G proteins. Since
      the cloning of the first GPCR, insights gained from structure-function studies,
      genetics and drug development have contributed to uncovering a common mechanism
      that explains the activation of diverse GPCRs by their cognate agonists. This
      mechanism takes into consideration the conservation of the structure-function
      relationship in the basic seven transmembrane structural motif, and the dynamic
      changes in receptor conformation that are associated with activation. Combining
      models derived from the X-ray structure of rhodopsin with structure-function data
      allows a deeper understanding of the activation mechanism of GPCRs.

PMID- 14580762
TI  - Vitamin D and prostate cancer prevention and treatment.
AB  - Human prostate cells contain receptors for 1alpha,25-dihydroxyvitamin D, the
      active form of vitamin D. Prostate cancer cells respond to vitamin D(3) with
      increases in differentiation and apoptosis, and decreases in proliferation,
      invasiveness and metastasis. These findings strongly support the use of vitamin D
      based therapies for prostate cancer and/or as a second-line therapy if androgen
      deprivation fails. The association between either decreased sun exposure or
      vitamin D deficiency and the increased risk of prostate cancer at an earlier age,
      and with a more aggressive progression, indicates that adequate vitamin D
      nutrition should be a priority for men of all ages. Here we summarize recent
      advances in epidemiological and biochemical studies of the endocrine and
      autocrine systems associated with vitamin D and their implications for prostate
      cancer and in the evaluation of vitamin D(3) and its analogs in preventing and/or
      treating prostate cancer.

PMID- 14580764
TI  - Lack of parental origin specificity of altered alleles at 11p15 in testicular
      germ cell tumors.
AB  - Allelic imbalance (AI) at loci on chromosome 11 has been shown in several types
      of human solid tumors, including testicular germ cell tumors (TGCTs). In this
      study we have focused on the 11p15 region, which is known for its high density of
      imprinted genes. Highly polymorphic microsatellite markers were analyzed in a
      series of 71 TGCTs, and AI was observed in 28 of the tumors (39%) at one or more
      of the loci analyzed. The AI data were evaluated against the chromosome 11 copy
      number, determined by fluorescence in situ hybridization with a centromere
      specific probe. To evaluate preferential parental allele alterations, the
      patients' normal and tumor genotypes were compared with the parental genotypes.
      Both losses and gains of both paternal and maternal alleles were found, and this
      lack of parental origin specificity of the altered allele suggests that the
      remaining allele is not inactivated by imprinting. A smallest region of
      overlapping changes was identified between the markers D11S2351 and D11S2347. In
      summary, our results support the theory that a nonimprinted 11p15 tumor
      suppressor gene is involved in the development of a subgroup of TGCTs.

PMID- 14580765
TI  - Pronounced chromosomal instability and multiple gene amplifications characterize
      ulcerative colitis-associated colorectal carcinomas.
AB  - Patients with ulcerative colitis have a significantly increased lifetime risk for
      the development of colorectal carcinomas. While genetic and genomic changes
      during carcinogenesis have been thoroughly studied in sporadic colorectal
      cancers, less is known about ulcerative colitis-associated colorectal carcinomas.
      The aim of this study was to extend the identification of specific genomic
      imbalances to ulcerative colitis-associated colorectal carcinomas and to
      establish a comprehensive map of DNA gains and losses by investigating 23 tumor
      specimens from 23 patients. The molecular cytogenetic characterization was
      performed using comparative genomic hybridization; immunohistochemistry was used
      to measure proliferative activity and laminin-5 expression as a marker for
      invasiveness. The results indicate that these tumors are invariably aneuploid,
      with a high proliferative activity and increased invasive potential. The average
      number of copy alterations correlates with increased cyclin A levels (P=0.044),
      which is an independent predictor of risk of carcinoma development in ulcerative
      colitis. Despite severe genetic instability, the general pattern of specific
      chromosomal aberrations that defines sporadic colorectal carcinomas is maintained
      in ulcerative colitis-associated malignancies. High-level copy number increases
      (amplifications) are dispersed throughout the genome. Strikingly, these
      amplifications are much more frequent than in sporadic carcinomas and map to
      chromosomal regions that have not been described before.

PMID- 14580766
TI  - Genesis of variant Philadelphia chromosome translocations in chronic myelocytic
      leukemia.
AB  - The Philadelphia (Ph) chromosome is found in more than 90% of chronic myelocytic
      leukemia (CML) patients. In most cases, it results from the reciprocal
      t(9;22)(q34;q11), with the ABL proto-oncogene from 9q34 fused to the breakpoint
      cluster region (BCR) locus on 22q11. In 5%-10% of patients with CML, the Ph
      chromosome originates from variant translocations, involving various breakpoints
      in addition to 9q34 and 22q11. In our investigation, three CML cases with complex
      Ph translocations have been analyzed by G-banding and fluorescence in situ
      hybridization (FISH). FISH with breakpoint-spanning probes for the BCR and ABL
      genes revealed information about the genesis of complex Ph translocations. The
      occurrence of one fusion signal indicates a one-step mechanism (case 1). Two
      fusion signals indicate a two-step mechanism (case 2). Lack of signals indicates
      deletions of parts of the BCR and ABL genes or of adjacent regions (case 3).

PMID- 14580767
TI  - Detection of genetic alterations in Korean ovarian carcinomas by degenerate
      oligonucleotide primed polymerase chain reaction-comparative genomic
      hybridization.
AB  - Chromosomal aberrations in 22 Koreans with ovarian carcinomas were investigated
      by degenerate oligonucleotide primed-polymerase chain reaction comparative
      genomic hybridization. The common sites of copy number increases were 20q (90%),
      17q23 approximately qter (86%), 8q22 approximately qter (68%), 3q25 approximately
      qter (59%), 6p21 (59%), 11q13 (54%), 16p (40%), 2q31 approximately qter (36%), 7q
      (36%), 14q31 (36%), 15q24 approximately qter (36%), and 1q32 approximately qter
      (31%). DNA amplification was identified in 18 carcinomas (82%). The frequent
      sites of amplification were 20q13.2 approximately qter, 8q24.1, 17q23
      approximately qter, 3q25 approximately qter, and 6p21. The most frequent sites of
      copy number decreases were 4q21 approximately q31 (54%), 5q13 approximately q21
      (50%), and 13q14 approximately q21 (45%). The recurrent gains and losses of
      chromosomal regions identified in this study provide candidate regions that may
      contain oncogenes or tumor suppressor genes, respectively.

PMID- 14580768
TI  - Comprehensive genome-wide comparison of DNA and RNA level scan using microarray
      technology for identification of candidate cancer-related genes in the HL-60 cell
      line.
AB  - Genome-wide scans for DNA and RNA changes in the HL-60 cell line relative to
      normal leukocytes were conducted. Microarray-based comparative genome
      hybridization (CGH) studies were performed with the Spectral Genomics Human
      Bacterial Artificial Chromosome (BAC) 3MB system. Transcriptional measurements of
      approximately 12,500 human genes were monitored using Affymetrix U95A GeneChips.
      In HL-60, genomic DNA amplification of the 8q24 locus, trisomy 18, and deletions
      at loci 5q11.2 approximately q31, 6q12, 9p21.3 approximately p22, 10p12
      approximately p15, 14q22 approximately q31, 17p12 approximately p13.3, and
      monosomy X were detected. After obtaining locus information about the RNA
      transcripts from the Affymetrix database, 4368 genes were stratified both
      according to status of RNA expression and the DNA copy number of their designated
      loci. The expression level of 2326 (53.25%) of 4368 transcripts is concordant
      with DNA copy number. Examples of specific, highly expressed, cancer-associated
      genes in amplified loci include SERPINB10, MYC, TYMS, HEC, and EPB41L3, while
      CD14, GZMK, TCF7, FOS, MLH3, CTNNA1, IRF1, VIM, CRK, MAP3K1, STAM, MAX, SFRG5,
      ENC1, PURA, MNT, RASA1, GLRX, UBE2B, NR3C1, PTENP1, BS69, COPEB, SKIP, PIM2, and
      MIC2 represent cancer-associated genes in deleted loci with decreased expression.
      The complementary usage of genome-wide DNA and RNA scans should enhance the
      identification of candidate genes in the neoplastic process.

PMID- 14580769
TI  - High levels of chromosomal imbalances in typical and small-cell variants of T
      cell prolymphocytic leukemia.
AB  - T-cell prolymphocytic leukemia (T-PLL) is a rare postthymic T-cell disorder that
      may show different morphologic variants and a very aggressive clinical behavior.
      On occasion, patients may present with an indolent clinical course and long
      survival. The disease is genetically characterized by the presence of complex
      karyotypes with recurrent alterations involving chromosomes 8, 14, and 11. The
      possible relationship between genetic alterations and morphologic variants and
      the clinical course of the disease, however, is not well known. Comparative
      genomic hybridization (CGH) was used to detect chromosomal imbalances in eight
      patients diagnosed with T-PLL, including three cases of small-cell variant with
      an indolent clinical evolution. Abnormal profiles were detected in all cases. The
      chromosomal regions most often over-represented were 8q (75%), 5p (62%), and 14q
      (37%), as well as 6p and 21 (both 25%). The chromosomal regions most often
      underrepresented were 8p and 11q (75%), 13q (37%), and 6q, 7q, 16q, 17p, and 17q
      (25%). The number of chromosomal imbalances in the three small-cell variants was
      relatively similar to that of cases with typical morphology. Only gains of 6p and
      losses of 7q present in three and two cases, respectively, with typical
      morphology were not detected in any small-cell variant. CGH analysis revealed
      alterations in 15 chromosomal regions not detected by conventional cytogenetics.
      These results indicate that T-PLL carry a high number of chromosomal alterations
      that are not related to the morphologic variants or the clinical behavior of the
      disease.

PMID- 14580770
TI  - Deletions of 17p are associated with transition from early to advanced colorectal
      cancer.
AB  - Several chromosome defects parallel morphologic evolution in colorectal tumor
      progression. Allelic losses in the short arm of chromosome 17, the majority
      encompassing the 17p13.3 band, have been found in advanced cancer in the absence
      of TP53 mutations, suggesting that loss of genes in this chromosome region is
      relevant for tumorigenesis. The aim of this study was to investigate 17p13.3
      deletions throughout the colorectal tumor progression using two-color
      fluorescence in situ hybridization. Histologic sections from 20 colorectal
      adenomas containing early invasive carcinoma were analyzed by interphase
      fluorescence in situ hybridization using a centromeric probe for chromosome 17
      simultaneously with a subtelomeric probe mapping to the 17p13.3 band. Separate
      evaluation was made for sectors corresponding to adenoma tissue with low-grade
      dysplasia, high-grade dysplasia, and early cancer. The same technique was also
      used in 20 cases of advanced adenocarcinoma of the large bowel. Loss of one
      centromeric signal was observed in 20, 40, 50, and 10% of low-grade dysplasia,
      high-grade dysplasia, early cancer, and advanced cancer, respectively (P<0.02
      early vs. advanced cancer). Subtelomeric 17p deletions were seen in 60% of
      advanced cancer and in 15% of early cancer (P<0.01). These findings indicate that
      loss of genes from the 17p13.3 chromosome region may play an important role in
      sustaining the transition from early to advanced cancer in colorectal tumor
      progression.

PMID- 14580771
TI  - Cytogenetic heterogeneity and progression of esophageal squamous cell carcinoma.
AB  - It is widely believed that most human tumors, including esophageal squamous cell
      carcinoma (ESCC), arise through multistep genetic and cytogenetic alterations.
      The time sequence of these alterations, however, is still unknown. The present
      study was designed to differentiate common early changes from uncommon later ones
      with combined comparative genomic hybridization (CGH) and ploidy analyses in
      multiple or single samples of 12 ESCCs. We first demonstrated that the mean copy
      numbers of chromosomes 3 and 11, determined directly by fluorescence in situ
      hybridization, showed linear correlation with the mean copy numbers calculated
      from the G/R ratio of CGH and DNA ploidy (R(2)=0.714, P<0.0001). On this basis,
      we estimated the absolute copy numbers of chromosomal parts by applying the
      ploidy-dependent threshold criteria to the G/R ratio data after the criteria were
      corrected by the percentage of tumor cells in each sample. One-copy changes in
      the DNA-diploid stage may give large shifts of the G/R ratio, even after
      tetraploidization, whereas those after tetraploidization undergo small shift.
      Using the tumors with multiple samples, it was actually demonstrated that most of
      the gains common to the samples in individual tumors showed the large shifts.
      Though early changes varied from tumor to tumor in the nine informative cases, it
      was found that gains of 3q (5/7: number of cases with large-shift 3q+/total
      number of cases with 3q+), 8q (3/4), 11q13 (4/5), and 14q (3/4) were early
      events, while losses of 3p (2/8), 5q (1/5), 13q (1/5), and 21q (1/5), and gains
      of 1p (1/4) and Xq (1/4) were later events in progression of individual tumors.

PMID- 14580772
TI  - Comparative cytogenetic and DNA flow cytometric analysis of 242 primary breast
      carcinomas.
AB  - The cytogenetic and DNA flow cytometric findings in 242 breast carcinomas were
      compared. The combined use of both techniques improved the detection of abnormal
      cell populations from 65% by cytogenetic analysis alone and 59% by DNA flow
      cytometric analysis alone to 84%. Informative and comparable cytogenetic and flow
      cytometric data were obtained for 155 tumors. Among these 155 tumors, there was
      good concordance (64%) between the estimates of genomic changes by the two
      methods. Most discrepancies were among the DNA-diploid cases, where cytogenetic
      analysis detected small genomic changes. There were, however, also some
      exceptions in which large genomic changes detected by one method were missed by
      the other. Of the specific breast cancer-associated cytogenetic aberrations
      subjected to separate correlation analysis, polysomy for chromosome 20 was
      significantly associated with a high S-phase fraction, whereas loss of the long
      arm of chromosome 16 and/or the presence of a der(1;16) were significantly
      associated with a low S-phase fraction. Our data show that cytogenetic and DNA
      flow cytometric analyses of breast carcinomas give largely comparable results,
      and that combining data from both methods significantly improves the information
      obtained by either technique used alone on the genetic abnormalities in these
      tumors.

PMID- 14580773
TI  - Diffuse large B-cell lymphoma with occult marrow involvement and a novel
      t(9;10)(q32;q22).
AB  - A 33-year-old man was found to have stage IV diffuse large cell lymphoma with
      visceral, cutaneous, and central nervous system involvement. Although examination
      of the posttreatment bone marrow failed to show morphologic evidence of lymphoma
      involvement, cytogenetic study of the marrow mononuclear cells showed the
      presence of a clonal abnormality t(9;10)(q32;q22), a hitherto undescribed
      chromosomal abnormality in diffuse large B-cell lymphoma.

PMID- 14580774
TI  - Polymorphism in the hMSH2 gene (gIVS 12-6T-->C) and risk of non-Hodgkin lymphoma
      in a Japanese population.
AB  - We conducted a hospital-based prevalent case-control study in a Japanese
      population (cases=103, controls=487) to ascertain the previous report about the
      association between the polymorphism in exon 13 of the hMSH2 gene (gIVS 12-6T-
      >C) and the risk of non-Hodgkin lymphoma in an Ecuadorian population. When the TT
      genotype was defined as the reference, none of the CT genotypes (OR=1.52; 95% CI,
      0.97-2.37), CC genotypes (OR=1.06, 95% CI, 0.44-2.54), or CT and CC genotypes
      combined together (OR=1.44, 95% CI, 0.94-2.23) demonstrated significant OR.
      Further investigations with sufficiently larger populations and in other
      ethnicities are required to verify this association.

PMID- 14580775
TI  - A case of Down syndrome with acute lymphoblastic leukemia and isochromosome Xp.
AB  - A 3-year, 9-month-old girl with trisomy 21 was diagnosed with acute lymphoblastic
      leukemia (ALL). The karyotype of her leukemic cells at diagnosis
      48,XX,+i(X)(p10),+21c-included an extra, structurally abnormal X chromosome as
      the sole acquired abnormality. While an extra X chromosome is a common
      abnormality in childhood ALL, it is seldom the only acquired aberration.
      Furthermore, an additional X chromosome that is structurally abnormal is rare,
      and has not been reported previously as a solitary abnormality. Here we report a
      novel karyotype in childhood ALL and review the eight previously described cases
      of ALL with an extra X isochromosome as the only acquired abnormality.

PMID- 14580776
TI  - Clonal chromosome aberrations in Philadelphia-negative cells from chronic
      myelocytic leukemia patients treated with imatinib mesylate: report of two cases.
AB  - Imatinib mesylate (tested as STI571), an abl kinase inhibitor, induces sustained,
      complete hematologic and cytogenetic responses in chronic myelocytic leukemia
      (CML) patients; however, emergence of clonal chromosomal aberrations in
      Philadelphia-negative (Ph-) cells during treatment has been reported. We describe
      two CML patients in chronic phase who presented with complete cytogenetic
      responses during imatinib mesylate therapy but developed new clonal chromosomal
      rearrangements in Ph- cells. The first patient presented with a duplication of
      chromosome 1, dup(1)(q21q42), and the second showed two new clonal aberrations
      consisting of inv(1)(q12q32) and del(7)(q22) in the same clone.

PMID- 14580778
TI  - Identification of a BAC clone overlapping the t(6p12.3) breakpoint in the cell
      line ESS-1 derived from an endometrial stromal sarcoma.
AB  - A major subgroup of endometrial stromal sarcomas (ESS) is characterized by
      translocations involving chromosome 6 with consistent breakpoints at 6p11
      approximately p21. As part of an ongoing positional cloning effort to identify
      the genes affected by these translocations, this article reports on the
      delineation of the 6p breakpoint in the cell line ESS-1 derived from an ESS. The
      G- and 4',6-diamidino-2-phenylindole-banded karyotypes showed an unbalanced
      translocation described originally as der(3)t(3;6) (q29;p21.1). Fluorescence in
      situ hybridization using probes derived from contigous yeast artificial
      chromosome, bacterial artificial chromosome (BAC), and P1-derived artificial
      chromosome clones specific to 6p12.3 approximately p21.1 located the breakpoint
      at 6p to the BAC clone RP11-337K13 mapping to 6p12.3. The DNA sequence of the
      breakpoint region contained in RP11-337K13 will serve as a candidate locus for
      further molecular genetic analyses to isolate the gene(s) altered in ESS with 6p
      rearrangement.

PMID- 14580779
TI  - The chromosome 5q21 band minisatellite and head and neck cancer.

PMID- 14580777
TI  - Detection of cryptic MLL insertions using a commercial dual-color fluorescence in
      situ hybridization probe.
AB  - Involvement of the MLL gene located at chromosome region 11q23 is a frequent
      occurrence in both acute myelocytic leukemia and acute lymphoblastic leukemia.
      More than 30 loci have now been associated with MLL, usually by reciprocal
      translocation. Deletions, insertions, and more complex rearrangements of MLL are
      rarely seen. We present three cases of AML M5 showing no cytogenetic evidence of
      11q23 rearrangement, in which a commercial MLL dual-color fluorescence in situ
      hybridization probe revealed a nonstandard abnormal signal pattern, suggesting
      cryptic insertion of the MLL gene into its partner gene site.

PMID- 14580780
TI  - Molecular and cellular mechanisms of cadmium carcinogenesis.
AB  - Cadmium is a heavy metal, which is widely used in industry, affecting human
      health through occupational and environmental exposure. In mammals, it exerts
      multiple toxic effects and has been classified as a human carcinogen by the
      International Agency for Research on Cancer. Cadmium affects cell proliferation,
      differentiation, apoptosis and other cellular activities. Cd2+ does not catalyze
      Fenton-type reactions because it does not accept or donate electrons under
      physiological conditions, and it is only weakly genotoxic. Hence, indirect
      mechanisms are implicated in the carcinogenicity of cadmium. In this review
      multiple mechanisms are discussed, such as modulation of gene expression and
      signal transduction, interference with enzymes of the cellular antioxidant system
      and generation of reactive oxygen species (ROS), inhibition of DNA repair and DNA
      methylation, role in apoptosis and disruption of E-cadherin-mediated cell-cell
      adhesion. Cadmium affects both gene transcription and translation. The major
      mechanisms of gene induction by cadmium known so far are modulation of cellular
      signal transduction pathways by enhancement of protein phosphorylation and
      activation of transcription and translation factors. Cadmium interferes with
      antioxidant defense mechanisms and stimulates the production of reactive oxygen
      species, which may act as signaling molecules in the induction of gene expression
      and apoptosis. The inhibition of DNA repair processes by cadmium represents a
      mechanism by which cadmium enhances the genotoxicity of other agents and may
      contribute to the tumor initiation by this metal. The disruption of E-cadherin
      mediated cell-cell adhesion by cadmium probably further stimulates the
      development of tumors. It becomes clear that there exist multiple mechanisms
      which contribute to the carcinogenicity of cadmium, although the relative weights
      of these contributions are difficult to estimate.

PMID- 14580781
TI  - 17alpha-methyltestosterone: 28-day oral toxicity study in the rat based on the
      "Enhanced OECD Test Guideline 407" to detect endocrine effects.
AB  - A 28-day oral gavage toxicity study in the rat with 17alpha-methyltestosterone
      was conducted as part of the international validation exercise on the modified
      Enhanced OECD Test Guideline 407 (Organisation for Economic Co-operation and
      Development, Paris). Special emphasis was placed on the endocrine mediated
      effects exerted by 17alpha-methyltestosterone, a potent androgen agonist. The
      test compound was administered daily by oral gavage for at least 28 days to
      groups of 7-week-old-Wistar rats. Dose levels were 0, 10, 40 and 200 mg/kg body
      weight per day for males and 0, 10, 100 and 600 mg/kg body weight per day for
      females. In addition, and outside the remit of the enhanced protocol,
      testosterone levels in males, oestradiol levels in females and luteinizing
      hormone (LH) levels in both sexes were measured, to provide a broader profile on
      the hormonally mediated effects of 17alpha-methyltestosterone. Furthermore, stage
      specific quantification of Terminal deoxynucleotidyl transferase-mediated dUTP
      Nick-End Labeling (TUNEL)-labeled germ cells (apoptotic germ cells) in the
      seminiferous tubules was also performed, in an effort to demonstrate the precise
      stages in the spermatogenic cycle 17alpha-methyltestosterone exerts its effect.
      In this study, the most critical additional parameters contained in the Enhanced
      OECD Test Guideline 407 for the detection of endocrine disruption were considered
      to be the histopathological assessment and organ weight data of endocrine-related
      tissues. Beyond the scope of this validation exercise, an increase in apoptosis
      in specific germ cell types was detected using the TUNEL assay in male rats
      treated at 200 and 40 mg/kg.

PMID- 14580782
TI  - Susceptibility to cartap-induced lethal effect and diaphragmatic injury via
      ocular exposure in rabbits.
AB  - Cartap is extensively used to control agricultural pests. Pertinent literatures
      have indicated that it causes no eye irritation [D.E. Ray, Insecticides derived
      from plants and other organisms, in: W.J. Hayes, E.R. Laws (Eds.), Handbook of
      Insecticide Toxicology, Classes of Insecticides, vol. 2, Academic Press, New
      York, 1991, p. 611; C. Tomlin, Cartap, in: C. Tomlin (Ed.), The Insecticide
      Manual, 12th ed., British Crop Protection Council, Surrey, UK, 2000, p. 144];
      however, the instillation of a little cartap through the eye has caused death in
      rabbits. The aim of this study was to determine the ocular toxicity of cartap in
      New Zealand White rabbits. Cartap was directly instilled into the low
      conjunctival sac of eyes, at doses of 0, 5, 7.5, 10 and 12.5 mg/kg body weight.
      The changes in the enzymes and isoenzymes of creatine kinase (CK), lactate
      dehydrogenase (LD), as well as pathological changes in the muscles of the heart,
      thigh and diaphragm were determined in the cartap-treated rabbits. Moreover, the
      neuromuscular effect of cartap was examined using the isolated rabbit phrenic
      nerve diaphragm model. The results indicated that rabbits developed severe signs
      and they died within 20 min of ocular instillation. The ocular LD50 of cartap was
      8.1 mg/kg body weight. Treatment with cartap increased the activities of CK and
      LD enzymes and their isoenzymes, CK-1, CK-2, and CK-3 in serum, and CK-3 and LD-5
      in the diaphragm. Microscopically, hypercontraction bands and the rupture of
      myofibers of the diaphragm were observed in dead rabbits. Cartap did not affect
      nerve-evoked twitch but induced irreversible contracture and twitch depression on
      the isolated rabbit's diaphragm. These results indicate that the rabbit is
      susceptible to cartap toxicity; the effect of cartap caused contracture and
      damage to the diaphragm might play a pivotal role in respiratory paralysis and
      death of rabbits during intoxication.

PMID- 14580783
TI  - Impact of dietary exposure to methoxychlor, genistein, or diisononyl phthalate
      during the perinatal period on the development of the rat endocrine/reproductive
      systems in later life.
AB  - To evaluate the impact of dietary exposure to endocrine disrupting chemicals
      (EDCs) during the sensitive period of brain sexual differentiation, maternal
      Sprague-Dawley rats were fed three representative chemicals, methoxychlor (MXC;
      24, 240, and 1200 ppm), genistein (GEN; 20, 200, and 1000 ppm), or diisononyl
      phthalate (DINP; 400, 4000, and 20,000 ppm), from gestational day 15 to postnatal
      day 10. Soy-free diet was used as a basal diet to eliminate possible estrogenic
      effects from the standard diet. Offspring were examined in terms of anogenital
      distances, prepubertal organ weights, onset of puberty, estrous cyclicity, and
      organ weights and histopathology of endocrine organs at adult stage (week 11) as
      well as the volumes of sexually dimorphic nucleus of preoptic area (SDN-POA). All
      chemicals caused signs of maternal toxicity at high doses. MXC, at 1200 ppm,
      facilitated and delayed the onset of puberty in females and males, respectively,
      females also showing endocrine disrupting effects thereafter, such as irregular
      estrous cyclicity and histopathological alterations in the reproductive tract and
      anterior pituitary. GEN, at all doses, reduced body weight (BW) at week 11, but
      did not affect endocrine parameters. Treatment with DINP at 20,000 ppm resulted
      in degeneration of meiotic spermatocytes and Sertoli cells in the testis and
      decrease of corpora lutea in the ovary at week 11, although changes remained
      minimal or slight. The SDN-POA volume remained unchanged with all three
      chemicals. The results demonstrated that perinatal dietary exposure to EDCs for a
      limited period causes endocrine disruption in offspring only at high doses.

PMID- 14580784
TI  - Genotoxic effects of myosmine in human lymphocytes and upper aerodigestive tract
      epithelial cells.
AB  - Myosmine, 3-(1-pyrroline-2-yl)pyridine, is an alkaloid found in tobacco plants.
      Recently, it was also detected in various edibles and staple foods. Whereas other
      tobacco alkaloids such as nicotine and nornicotine and their nitrosation
      products, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N'
      nitrosonornicotine (NNN), have been widely discussed, the mutagenic impact of
      myosmine has not been investigated in detail. In the present study, possible
      genotoxic effects of myosmine were studied in human lymphocytes and nasal mucosal
      cells using the alkaline single cell microgel electrophoresis (Comet) assay. DNA
      single strand breaks, alkali labile sites and incomplete excision repair sites
      were expressed using the Olive tail moment (OTM). One hour incubation with
      myosmine at 0, 5, 10, 25 and 50 mM induced a low but significantly dose-dependent
      increase of DNA migration from 1.29 +/- 0.13 to 18.25 +/- 1.59 (OTM, mean +/-
      S.E., N=11) in lymphocytes. In nasal mucosal cells a similar although somewhat
      less extensive DNA damage from 1.17 +/- 0.12 to 21.67 +/- 2.97 (OTM, mean +/-
      S.E., N=10-11) was obtained after 1 h incubation with myosmine at 0, 10, 25, 50
      and 100 mM. After prolonged incubation of human lymphocytes with 10mM myosmine
      for 1, 3, 6, and 24 h, a significant time-dependent increase of DNA migration
      from 3.45 +/- 0.43 to 57.77 +/- 8.24 (OTM, mean +/- S.E., N=4) was observed. Our
      data indicate that myosmine expresses significant genotoxic effects in human
      target cells of carcinogenesis. This result warrants further investigations on
      the impact of this dietary component on human health.

PMID- 14580786
TI  - Four-week inhalation toxicity study in rats with nylon respirable fibers: rapid
      lung clearance.
AB  - This inhalation toxicity study in rats was conducted to assess the hazard
      potential for workers inhaling Nylon respirable fibers. Groups of 48 male rats
      each were exposed, nose-only, 6h per day, 5 days per week, for 4 weeks to
      aerosols of uncoated, finish-free Nylon respirable-sized, fiber-shaped
      particulates (RFP) at concentrations of 0, 4, 15 and 57 fibers (f)/cm3. Nylon
      RFPs were prepared using flock rotary cutters followed by vigorous opening
      procedures. After exposures, the lungs of sham and Nylon-exposed rats were
      assessed at 1 and 8 days, and 1, 3, 6 and 12 months postexposure. The results
      showed that the retained mean lung burdens at 1 day postexposure were 1.75E+07
      RFP/lung (high level). Mean lengths and diameters of the Nylon aerosol were 9.8
      and 1.6 microm, respectively. Lung clearance of Nylon RFPs was rapid over the 12
      month period. There were no significant increases in lung weights, indications of
      pulmonary inflammation, or alveolar macrophage functional deficits in Nylon
      exposed animals versus controls based on cell differentials, bronchoalveolar
      lavage (BAL) fluid analyses, and macrophage phagocytosis or chemotaxis activity.
      Histopathology revealed no adverse lower pulmonary or upper respiratory effects.
      In summary, the no-observed-effect level (NOEL) for inhaled Nylon RFP was 57f/cm3
      (20mg/m3), the highest concentration tested.

PMID- 14580785
TI  - Nitric oxide-dependent vasorelaxation and endothelial cell damage caused by
      mercury chloride.
AB  - Mercury and its derivatives are known to constrict vascular smooth muscle cells.
      However, little is known about the role of endothelial cells in mercury-induced
      vasoreactivity. Using isolated, norepinephrine preconstricted rat aorta and
      pulmonary artery rings with intact endothelium, we demonstrate that mercury
      chloride (HgCl2) induces an endothelial-dependent vasorelaxation which was
      totally blocked by the nitric oxide inhibitor L-NAME. Besides this vasorelaxant
      effect, treatment with HgCl2 resulted in functional and morphological alterations
      of the endothelial cells. On aortic rings, endothelial cells were partly lifted
      from the basal membrane when incubated for 20 min in HgCl2 (10(-7) M)-containing
      buffer. At a concentration of 10(-6) M, the endothelial cells were completely
      denuded and acetylcholine vasorelaxation was abolished. Endothelial cell
      structure and function was preserved by incubating the vessels in HgCl2
      containing rat blood instead of buffer. We conclude that HgCl2 induces an
      endothelial-dependent vasorelaxation and alters structure and function of
      vascular endothelial cells.

PMID- 14580787
TI  - Photodynamic toxicity and its prevention by antioxidative agents in Bufo arenarum
      embryos.
AB  - In this work we describe an experimental model to evaluate the photodynamic
      toxicity on amphibian embryos, as well as the protective effect of antioxidants
      against the lethal oxidative stress induced by photosensitization. Bufo arenarum
      embryos were treated with 10 mg/l methylene blue (MB) in AMPHITOX solution for 72
      h and then irradiated with a red laser or white light for variable times. Both
      light sources affected the survival of MB-treated animals and lethal effects
      occurred within the initial 12 h post-irradiation. For white light irradiation,
      the most effective phototoxic condition in our study, the LD10, 50 and 90 at 6 h
      post-irradiation corresponded to 13.57, 19.87 and 29.10 J/cm2, respectively. To
      explore the action of antioxidants against the photogenerated oxidative stress,
      MB-treated embryos were incubated with 1mM glutathione (GSH) or ascorbic acid
      (AA) during 48 h before irradiation. For GSH and 21.6 J/cm2 irradiation, the
      survival increased from 20 to 90%, whereas 100% survival was achieved with AA
      even after 43.2 J/cm2 irradiation. These results indicate that both the lethal
      photodynamic effect and its prevention by antioxidants can be evaluated by means
      of a simple toxicity test employing amphibian embryos.

PMID- 14580788
TI  - Sodium valproate induces apoptosis in the rat hepatoma cell line, FaO.
AB  - Sodium valproate (VPA) is clinically employed as an anti-convulsant and, to a
      lesser extent, mood stabilizer. While the incidence of toxicity associated with
      the clinical use of valproate is low, serious hepatotoxicity makes up a
      significant percentage. Rats treated with high doses of sodium valproate are
      subject to hepatotoxicity, and the study of the molecular mechanisms underlying
      this phenomenon may shed further light on the human situation. Exposure to sodium
      valproate results in the down regulation in rat liver of several transcripts
      whose products are involved in cellular energy homeostasis, resulting in time
      dependent fluctuations in cellular ATP, possibly resulting in cell death. To
      further examine this, classical markers of apoptosis were examined in the rat
      hepatoma cell line FaO following sodium valproate exposure. Concentrations
      greater than 300 microM sodium valproate resulted in a transient wave of
      apoptosis, as assessed by chromatin condensation and DNA fragmentation assay.
      Analysis indicated that Fas-ligand and caspase-11 expression were increased at
      the transcriptome level, while caspase-3 was activated at the proteome level
      during the exposure period. These data demonstrates that sodium valproate causes
      cell death through apoptosis in a rat liver cell line, and provides information
      on the possible molecular mechanisms underlying this phenomenon in vivo.

PMID- 14580789
TI  - Oxidative DNA damage and repair in skeletal muscle of humans exposed to high
      altitude hypoxia.
AB  - Recent research suggests that high-altitude hypoxia may serve as a model for
      prolonged oxidative stress in healthy humans. In this study, we investigated the
      consequences of prolonged high-altitude hypoxia on the basal level of oxidative
      damage to nuclear DNA in muscle cells, a major oxygen-consuming tissue. Muscle
      biopsies from seven healthy humans were obtained at sea level and after 2 and 8
      weeks of hypoxia at 4100 m.a.s.l. We found increased levels of strand breaks and
      endonuclease III-sensitive sites after 2 weeks of hypoxia, whereas oxidative DNA
      damage detected by formamidopyrimidine DNA glycosylase (FPG) protein was
      unaltered. The expression of 8-oxoguanine DNA glycosylase 1 (OGG1), determined by
      quantitative RT-PCR of mRNA levels did not significantly change during high
      altitude hypoxia, although the data could not exclude a minor upregulation. The
      expression of heme oxygenase-1 (HO-1) was unaltered by prolonged hypoxia, in
      accordance with the notion that HO-1 is an acute stress response protein. In
      conclusion, our data indicate high-altitude hypoxia may serve as a good model for
      oxidative stress and that antioxidant genes are not upregulated in muscle tissue
      by prolonged hypoxia despite increased generation of oxidative DNA damage.

PMID- 14580790
TI  - DNA fragmentation, apoptosis and cell cycle arrest induced by zearalenone in
      cultured DOK, Vero and Caco-2 cells: prevention by Vitamin E.
AB  - Zearalenone (ZEN) is a non-steroidal oestrogenic mycotoxin produced by several
      Fusarium species growing on cereals. ZEN and its metabolites bind to human
      oestrogen receptors and hence display oestrogenic and anabolic properties.
      Several lines of investigation suggest that ZEN may be genotoxic in vivo. ZEN
      damages DNA in Bacillus subtilis recombination tests, and it induces sister
      chromatid exchange and chromosomal aberration in CHO cells. ZEN also induces DNA
      adduct formation in mouse tissues and SOS repair process in lysogenic bacteria.
      In the present study, ZEN genotoxicity has been confirmed in three cell-lines,
      Vero, Caco-2 and DOK at concentrations of 10, 20 and 40 microM. Under these
      conditions, ZEN induces concentration-dependent DNA fragmentation resulting in
      DNA laddering patterns on agarose gel electrophoresis. This observation is
      consistent with apoptosis, which was confirmed by observations of formation of
      apoptotic bodies. Moreover, ZEN induces cell cycle arrest in the three cell-lines
      characterised by an increase of the number of cells in the G2/M phase of the cell
      cycle. Vitamin E (25 microM) added simultaneously with ZEN partially reduces DNA
      fragmentation and apoptotic body formation after 24h incubation. Vitamin E may
      act by maintaining prolonged cell cycle arrest during which time DNA repair takes
      place.

PMID- 14580791
TI  - Reducing acute poisoning in developing countries--options for restricting the
      availability of pesticides.
AB  - Hundreds of thousands of people are dying around the world each year from the
      effects of the use, or misuse, of pesticides. This paper reviews the different
      options to reduce availability of the most hazardous chemicals, focusing on
      issues in developing countries. Emphasis is placed on the fatal poisoning cases
      and hence the focus on self-harm cases. Overall, it is argued here that
      restricting access to the most hazardous pesticides would be of paramount
      importance to reduce the number of severe acute poisoning cases and case
      fatalities and would provide greater opportunities for preventive programmes to
      act effectively. The aim should be to achieve an almost immediate phasing out of
      the WHO Classes I and II pesticides through national policies and enforcement.
      These short-term aims will have to be supported by medium- and long-term
      objectives focusing on the substitution of pesticides with safe and cost
      effective alternatives, possibly guided by the establishment of a Minimum
      Pesticide List, and the development of future agricultural practices where
      pesticide usage is reduced to an absolute minimum. Underlying factors that make
      individuals at risk for self-harm include domestic problems, alcohol or drug
      addiction, emotional distress, depression, physical illness, social isolation or
      financial hardship. These should be addressed through preventive health
      programmes and community development efforts.

PMID- 14580792
TI  - Production of supercoiled multimeric plasmid DNA for biopharmaceutical
      application.
AB  - Production of nucleic acids as an active pharmaceutical ingredient (API) in gene
      therapy and genetic vaccination is gaining more and more importance. Non-viral
      vectors like plasmid DNA are currently investigated in various clinical trials.
      Supercoiled multimeric plasmids are of particular interest for pharmaceutical
      purpose because they contain multiple copies of a therapeutic gene and can
      therefore be more efficient vectors. A process for the preparation of Escherichia
      coli strains replicating dimers, trimers, and tetramers of a 4.6 kb plasmid is
      presented. Cultivation of these clones on semi-defined glycerol medium in a 7 l
      bioreactor shows structural stability of dimers and trimers during the whole
      cultivation process. Plasmid concentrations and selectivities are compared to the
      corresponding cultivation with the plasmid monomer. Cultivation of the tetramer
      replicating strain shows a disintegration of the plasmid multimer and
      reconstitution of the monomer and smaller multimers.

PMID- 14580793
TI  - A recombinant H1 histone-based system for efficient delivery of nucleic acids.
AB  - We describe here a unique transfer system based on a truncated form of the human
      linker histone H1F4 for the delivery of nucleic acids to a variety of cells. The
      efficiency of truncated histone H1.4F was assessed using both primary mammalian
      and immortalised insect and mammalian cell lines. Our results indicated that
      recombinant histone H1.4F was able to deliver DNA, dsRNA and siRNA in all cells
      tested. Quantitative analysis based on reporter gene expression or silencing of
      target genes revealed that the transfection efficiency of histone H1.4F was
      comparable to, or better than, liposome-based systems. Notably, the efficiency of
      histone H1.4F was associated with very low toxicity for transfected cells. The
      human H1.4F recombinant protein is easily purified in large-scale from bacterial
      lysates using inexpensive simplified processing. This versatile transfection
      system represents an important advance in the field of gene delivery and an
      improvement over earlier nucleic acid delivery methods.

PMID- 14580794
TI  - Multiplex polymerase chain reaction/membrane hybridization assay for detection of
      genetically modified organisms.
AB  - To improve detection efficiency and result accuracy, four screening primer pairs,
      four identifying primer pairs, one common primer pair and corresponding probes
      were designed for the development of multiplex polymerase chain reaction/membrane
      hybridization assay (MPCR-MHA) for detection of the foreign genes insert in
      genetically modified organisms (GMOs). After detecting condition and parameter
      were optimized and determined, MPCR reactions were developed for amplifying
      several target genes simultaneously in one tube. Primers were labeled with biotin
      at the 5'-end; biotinylated MPCR products were detected by hybridization to the
      oligonucleotide probes immobilized on a membrane with subsequent colorimetric
      detection to confirm hybridization. The testing of screening primers can judge
      whether the sample contains GMOs, and that of identifying primers can further
      judge what kinds of trait genes are contained in the sample. We detected nine
      soybean samples, six maize samples, seven potato samples and two rice samples by
      the MPCR-MHA method; at the same time we also detected them with single PCR-MHA
      method. The results between two methods have good consistency.

PMID- 14580796
TI  - Catabolism of volatile sulfur compounds precursors by Brevibacterium linens and
      Geotrichum candidum, two microorganisms of the cheese ecosystem.
AB  - Two Brevibacterium linens strains and the cheese-ripening yeast Geotrichum
      candidum were compared with regard to their ability to produce volatile sulfur
      compounds (VSCs) from three different precursors namely L-methionine, 4
      methylthio-2-oxobutyric acid (KMBA) and 4-methylthio-2-hydroxybutyric acid
      (HMBA). All microorganisms were able to convert these precursors to VSCs.
      However, although all were able to produce VSCs from L-methionine, only G.
      candidum accumulated KMBA when cultivated on this amino acid, contrary to B.
      linens suggesting that the transamination pathway is not active in this
      microorganism. Conversely, a L-methionine gamma-lyase activity--which catalyses
      the one step L-methionine to methanethiol (MTL) degradation route--was only found
      in B. linens strains. Several other enzymatic activities involved in the
      catabolism of the precursors tested were investigated. KMBA transiently
      accumulated in G. candidum cultures, and was then reduced to HMBA by a KMBA
      dehydrogenase (KDH) activity. This activity was not detected in B. linens.
      Despite no HMBA dehydrogenase (HDH) was found in G. candidum, a strong HMBA
      oxidase (HOX) activity was measured in this microorganism. This latter activity
      was weakly active in B. linens. KMBA and HMBA demethiolating activities were
      found in all the microorganisms. Our results illustrate the metabolic diversity
      between cheese-ripening microorganisms of the cheese ecosystem.

PMID- 14580795
TI  - Experimental modelling of thermal inactivation of urease.
AB  - Thermal inactivation of jack bean urease (EC 3.5.1.5) was investigated in a 0.1 M
      phosphate buffer with pH 7. An injection flow calorimetry method was adapted for
      the measurement of the enzyme activity. The inactivation curves were measured in
      the temperature range of 55 to 87.5 degrees C. The curves exhibited a biphasic
      pattern in the whole temperature range and they were well fitted with a
      biexponential model. A simultaneous fit of all inactivation data was based on
      kinetic models that were derived from different inactivation mechanisms and
      comprised the material balances of several enzyme forms and the enthalpy balance
      characterizing the initial heating period of enzyme solution. The
      multitemperature evaluation revealed that an adequate model had to incorporate at
      least three reaction steps. It was concluded that the key reaction steps at
      urease thermal inactivation were the reversible dissociation/denaturation of
      native form into an inactive denatured form, and irreversible association
      reactions of both the denatured and native forms.

PMID- 14580797
TI  - Magnetic alginate microparticles for purification of alpha-amylases.
AB  - Spherical magnetic alginate microparticles (25-60 microm in diameter) were
      prepared using the microemulsion system, with water-saturated 1-pentanol as the
      organic phase. The limited solubility of 1-pentanol in water enabled simple
      removal of the organic solvent from the prepared beads with water solution. The
      prepared alginate microparticles were used as magnetic affinity adsorbents for
      specific purification of alpha-amylases. Enzyme activity was eluted by 1.0 M
      maltose. alpha-Amylases from Bacillus amyloliquefaciens and porcine pancreatic
      acetone powder were purified 9- and 12-fold with 88 and 96% activity recovery,
      respectively.

PMID- 14580798
TI  - Attainment of endemic stability to Babesia bigemina in cattle on a South African
      ranch where non-intensive tick control was applied.
AB  - The seroprevalence of Babesia bigemina and Babesia bovis antibodies in non
      vaccinated cattle was monitored on a South African ranch. The main objective was
      to assess the endemic stability to bovine babesiosis in cattle maintained under
      relaxed tick-control measures. Cattle were bled at the age of 7, 8, 10, 17, 20
      and 30-120 months and the sera tested for the presence of antibodies using the
      indirect fluorescent antibody (IFA) test. None of the animals were positive to B.
      bovis. Seroprevalence of B. bigemina antibodies was 46, 70, 90, 92, 54 and 82% in
      the various age classes, respectively. Endemic stability was therefore reached by
      the time the calves were 9 months old. The high seroprevalence of B. bigemina was
      probably due to the high vector tick population on the ranch, which would have
      encouraged frequent transmission of B. bigemina. An endemically stable situation
      to B. bigemina could therefore be achieved merely by adopting a tick-control
      method that allows a reasonable number of ticks on cattle rather than relying
      entirely on intensive tick control and vaccination.

PMID- 14580799
TI  - Toxoplasma gondii, Neospora caninum, Sarcocystis neurona, and Sarcocystis canis
      like infections in marine mammals.
AB  - Toxoplasma gondii, Neospora caninum, Sarcocystis neurona, and S. canis are
      related protozoans that can cause mortality in many species of domestic and wild
      animals. Recently, T. gondii and S. neurona were recognized to cause encephalitis
      in marine mammals. As yet, there is no report of natural exposure of N. caninum
      in marine mammals. In the present study, antibodies to T. gondii and N. caninum
      were assayed in sera of several species of marine mammals. For T. gondii, sera
      were diluted 1:25, 1:50, and 1:500 and assayed in the T. gondii modified
      agglutination test (MAT). Antibodies (MAT > or =1:25) to T. gondii were found in
      89 of 115 (77%) dead, and 18 of 30 (60%) apparently healthy sea otters (Enhydra
      lutris), 51 of 311 (16%) Pacific harbor seals (Phoca vitulina), 19 of 45 (42%)
      sea lions (Eumetopias jubatus) [corrected] 5 of 32 (16%) ringed seals (Phoca
      hispida), 4 of 8 (50%) bearded seals (Erignathus barbatus), 1 of 9 (11.1%)
      spotted seals (Phoca largha), 138 of 141 (98%) Atlantic bottlenose dolphins
      (Tursiops truncatus), and 3 of 53 (6%) walruses (Odobenus rosmarus). For N.
      caninum, sera were diluted 1:40, 1:80, 1:160, and 1:320 and examined with the
      Neospora agglutination test (NAT) using mouse-derived tachyzoites. NAT antibodies
      were found in 3 of 53 (6%) walruses, 28 of 145 (19%) sea otters, 11 of 311 (3.5%)
      harbor seals, 1 of 27 (3.7%) sea lions, 4 of 32 (12.5%) ringed seals, 1 of 8
      (12.5%) bearded seals, and 43 of 47 (91%) bottlenose dolphins. To our knowledge,
      this is the first report of N. caninum antibodies in any marine mammal, and the
      first report of T. gondii antibodies in walruses and in ringed, bearded, spotted,
      and ribbon seals. Current information on T. gondii-like and Sarcocystis-like
      infections in marine mammals is reviewed. New cases of clinical S. canis and T.
      gondii infections are also reported in sea lions, and T. gondii infection in an
      Antillean manatee (Trichechus manatus manatus).

PMID- 14580800
TI  - Experimental infection of budgerigars (Melopsittacus undulatus) with a low
      virulent K21 strain of Toxoplasma gondii.
AB  - In total 53 budgerigars (Melopsittacus undulatus) were divided into six groups
      and orally infected with a suspension of oocysts of low virulent Toxoplasma
      gondii K21 strain in the doses of 10(2), 10(3), 10(4), 10(5) and 10(6),
      respectively. Blood was collected from the birds prior to the inoculation and
      then on days 10, 20 and 30 post infection. Latex-agglutination test (LAT) was
      used for the detection of antibodies in the inoculated birds. The infected birds
      showed no apparent signs of disease. The antibodies were found in all but two
      birds inoculated a dose of 10(2) oocysts. Haematological values remained
      unchanged after infection. T. gondii was isolated by bioassay in mice from all 37
      birds fed 10(3) or more oocysts and 6 of 9 fed 10(2) oocysts. The results
      demonstrate that budgerigars are resistant to T. gondii infection.

PMID- 14580801
TI  - Histopathological observations on the activity of diclazuril (Vecoxan) against
      the endogenous stages of Eimeria crandallis in sheep.
AB  - Doses of sporulated oocysts of Eimeria crandallis were administered to 60 housed
      lambs aged 3-4 weeks that had been raised coccidia-free. Thirty of the lambs were
      medicated with diclazuril at intervals over a 20-day period post-infection with
      the remaining lambs serving as untreated controls. Lambs were euthanased between
      5 and 22 days post-infection (dpi) and sections of the small intestine and caecum
      examined histologically. Untreated lambs showed loss of surface epithelial cells
      and villous atrophy associated with first-generation meronts, crypt destruction
      and crypt hyperplasia associated with pro-gamont stages. Diclazuril appeared to
      have a direct effect on several stages of the parasite life cycle, in particular,
      the large first-generation meront. Indications were that the drug also had an
      effect on second-generation meronts and gamont stages. Therapeutic benefits of
      diclazuril treatment appeared greatest when given early in the infection before
      damage to the intestine occurs although removal of coccidial stages did appear to
      reduce the pathology of the disease.

PMID- 14580802
TI  - Current status and epidemiological observation of Thelazia callipaeda (Spirurida,
      Thelaziidae) in dogs, cats and foxes in Italy: a "coincidence" or a parasitic
      disease of the Old Continent?
AB  - Thelazia callipaeda is a spirurid nematode which causes ocular infections in dogs
      and man and, occasionally, in cats, foxes and rabbits. The intermediate host and
      vector of T. callipaeda is unknown. For a long time T. callipaeda incidence was
      reported only from the Russian Federation and the Far East, but recently it has
      also been found in Italy. In order to investigate the spread of T. callipaeda in
      Italy, a survey was carried out in two sites, site A in the Piedmont region
      (North West Italy), and site B in the Basilicata region (Southern Italy). Dogs,
      cats and foxes in site A and dogs in site B were examined for eyeworms, using
      different procedures and timing. From January 1995 to August 2002, 91 dogs, 4
      cats and 903 fox carcasses were examined in site A, and from October 1999 to
      January 2003, 443 dogs were examined in site B, and the eyeworms collected were
      identified using morphological keys. Twenty-one (23.07%) and 185 (41.76%) of the
      dogs from sites A and B, respectively, were found to be infected by eyeworms;
      furthermore, all the cats examined and 46 fox carcasses (5.1%) were positive for
      eyeworms. All the nematodes collected were identified as T. callipaeda. These
      results indicate that T. callipaeda is not confined to Eastern Europe and Asia,
      but that it has spread to the Old Continent, and to both Northern and Southern
      Italy. Considering the high prevalence of infected dogs reported in some
      municipalities (e.g. 60.14% of 138 dogs examined in a municipality from site B),
      it is assumed that one or more vectors are significantly present in the areas
      under investigation. Furthermore, there is good reason to believe that T.
      callipaeda is also present in other European countries. Speculation as to the
      origins of this parasitic infestation in Europe and the biology of T. callipaeda
      and its vector/s is also discussed.

PMID- 14580803
TI  - Assessment of cypermethrin and doramectin for controlling wohlfahrtiosis in
      Crete.
AB  - The fleshfly, Wohlfahrtia magnifica, became an animal health problem in Crete,
      Greece, during 1999, causing outbreaks of wohlfahrtiosis throughout the main
      livestock producing regions of the island. The aim of this study was to determine
      the efficacy of commercially available drugs in order to design control
      strategies against wohlfahrtiosis. The test substances were cypermethrin and
      doramectin sc. The test animals were randomly divided between three groups (30 in
      each): one treated with cypermethrin pour-on, one treated with doramectin and one
      untreated controls. The trial lasted 45 days and the animals were inspected daily
      for natural infestations by W. magnifica. The first infestations were recorded on
      the 5th, 13th and the 23rd day in the control, cypermethrin and doramectin
      groups, respectively. There was a statistically significant difference between
      the survival curves for doramectin and the control group up to day 40, but not at
      the end of the study.

PMID- 14580804
TI  - Efficacy of injectable and pour-on microdose ivermectin in the treatment of goat
      warble fly infestation by Przhevalskiana silenus (Diptera, Oestridae).
AB  - The prophylactic efficacy of microdoses of injectable and pour-on ivermectin
      formulations against larval stages of Przhevalskiana silenus was assessed in
      naturally infected goats in the region of Calabria (southern Italy).Sixty-eight
      goats from two goat farms were divided into five groups: one group remained
      untreated, while the other four groups were treated with microdoses of ivermectin
      (5 and 10 microg/kg injectable formulation and 10 and 20 microg/kg pour-on
      formulation). The microdoses of ivermectin were fully effective in the treatment
      of goat warble fly infestation (GWFI) as no larvae emerged from the warbles in
      the treated groups, while all the larvae emerged in the control groups.
      Irrespective of the type of formulation used, the difference between the treated
      groups and the control group was statistically significant (P< 0.001). By
      contrast, no statistical differences were found between the goats treated with
      the injectable formulation and those receiving the pour-on applications, and
      between the two doses of the injectable and pour-on formulations used. Given the
      plasma concentrations it attains at its lowest dose (0.052 - 0.042 ng/ml for the
      injectable formulation and 0.030 ng/ml for the pour-on) the injectable
      formulation seems to offer the most reliable route for the administration of
      ivermectin microdoses and it is acceptable for milk consumption. The introduction
      of ivermectin in the early eighties and the use of microdoses in some cases have
      made it possible to control cattle hypodermosis in large areas of Europe. As with
      cattle hypodermosis, the administration of ivermectin microdoses in goats is
      particularly interesting because of the low costs involved and the low levels of
      residues found in goat milk; it may thus constitute the basis for GWFI control
      campaigns in areas where the disease is prevalent.

PMID- 14580805
TI  - Clinico-haematological and mineral studies on experimental maduramicin toxicity
      in chickens.
AB  - Clinico-haematological and mineral studies were carried out in experimental
      chickens given maduramicin medicated feed at 5 and 10 ppm for 21 days.
      Maduramicin medication in both medicated groups caused growth retardation.
      Clinical signs namely watery diarrhoea, depression, dullness and ruffled feathers
      were noticed in chickens from second week of the medication at 10 ppm but this
      effect was seen from third week in the birds given maduramicin at 5 ppm.
      Maduramicin medication caused significant reduction in haemoglobin in both the
      medicated group from day 14 and total erythrocyte count and packed cell volume in
      10 ppm group on day 21. There was an increase in MCV in 10 ppm group on day 21
      indicating macrocytic anaemia and decrease in mean corpuscular haemoglobin
      concentration (MCHC) in both the medicated groups indicating hypochromic anaemia.
      The leucopenia due to lymphopenia was observed in 10 ppm group on day 21.
      Maduramicin medication caused significant increase in serum Zn in 10 ppm group
      and decrease in Cu concentration in both the medicated groups from day 14. It is
      concluded that maduramicin caused toxic effects from day 14 in both the medicated
      groups.

PMID- 14580806
TI  - Characterisation of choline esterases and their tissue and subcellular
      distribution in mussel (Mytilus edulis).
AB  - Acetylcholinesterase in mussel is potentially a useful biomarker of exposure to
      organophosphates (OP) in the marine environment. This study looked at
      cholinesterase activity in subcellular fractions of various tissues from the
      common mussel, Mytilus edulis. Measurement of enzyme rates demonstrated that
      although highest specific activity was found in foot 'mitochondrial' fraction,
      recovery of activity was very low. Gill 'microsomal' fraction had the second
      highest specific activity with a useful level of recovery and therefore was the
      most suitable tissue fraction for biomarker applications. Comparative studies of
      alternative alkylthiocholine substrates and competitive inhibitors suggest there
      is a single cholinesterase enzyme type present in this fraction. Inhibition of
      alkylcholine hydrolysis by BW284C51, specific to acetylcholinesterase in
      vertebrates, showed that cholinesterase activity in gill 'microsomal' fraction is
      inhibited by this compound but to a lesser extent than in vertebrate AChE.
      Inhibition of cholinesterase activity by azamethiphos in gill 'microsomal'
      fraction gave an IC50 of approximately 100 microM and showed both time and
      concentration dependence. However this indicates a lower potency compared to
      other animals and it is debatable whether mussel cholinesterase activity is
      useful as a biomarker of exposure in the field.

PMID- 14580807
TI  - Bioaccumulation of trace metals in the amphipod Chaetogammarus marinus (Leach,
      1815) from the Avon and Tamar estuaries (UK): comparison of two-compartment and
      hyperbolic toxicokinetic models.
AB  - Bioaccumulation of Cd, Cr, Cu, Co, Pb, Ni and Zn was investigated in the
      eulittoral gammaridean amphipod Chaetogammarus marinus (Leach, 1815) from the
      Avon and Tamar estuaries (UK). The main goals were to provide information on
      accumulation strategies of the organisms tested and to verify toxicokinetic
      models as a predictive tool. The organisms accumulated metals upon exposure and
      it was possible to estimate significant model parameters of two-compartment and
      hyperbolic models, with the exception of Zn. Both types of models yielded
      significant model estimates in two independent toxicokinetic studies using
      gammarids from the Avon and Tamar estuaries, respectively. Kinetic BCFs at
      theoretical equilibrium were 58-102 for Cd, 95-215 for Cr, 400-963 for Cu, 38-59
      for Co, 150-750 for Pb and 33-63 for Ni, and were in most cases distinctly lower
      than the range reported in the literature for other amphipods. To demonstrate the
      potential of toxicokinetic models as a predictive tool, attempts were made,
      further to verify time-dependent model data (Tamar) with independent experimental
      data (Avon). In this case only for Cd were both in good agreement, whilst for all
      other elements the models overestimated the measured values. The second approach
      was to verify time-dependent model data (Tamar) with measured values from an
      independent concentration-dependent uptake study (Tamar) or, alternatively, to
      estimate the model parameters simultaneously for both studies. A good agreement
      between observed and predicted values was obtained for all elements for the
      simultaneous two-compartment models. Only for Cd was a simultaneous estimation of
      the hyperbolic model more promising. A tentative estimation showed the following
      sequence of sensitivity of C. marinus to an increase of soluble metal exposure:
      0.6 microg Cd l(-1), 1.7 microg Cr l(-1), 16 microg Cu l(-1), 3.5 microg Co l(
      1), 0.8 microg Pb l(-1) and 7 microg Ni l(-1). Available information can be used
      to quantify a measure of agreement or disagreement between bioaccumulation in
      different amphipods. This can be regarded as an important step in the calibration
      of biomonitors which is necessary to assess the potential for bioaccumulation on
      a large geographical scale.

PMID- 14580808
TI  - Evaluation of mussel immune responses as indicators of contamination in San
      Francisco Bay.
AB  - Several immune parameters were evaluated in two species of mussels (Mytilus
      californianus and M. galloprovincialis/M. trossulus) as bioindicators of
      contaminant effects. The mussels were deployed in San Francisco Bay Estuary and a
      control site at Bodega Marine Laboratory. Assays for phagocytosis and phagocytic
      index (average number of particles engulfed per hemocyte) were conducted with
      hemocytes in their own hemolymph-the "Serum" method. The responses were compared
      with contaminant concentrations in those mussels. For both species, the
      contaminated South Bay Dumbarton Bridge and Redwood Creek sites had elevated
      phagocytosis relative to the Bodega control site, indicating contaminant stress.
      The results also showed that M. californianus had higher percentages of
      phagocytosis (74%) and a higher phagocytic index (4.6 particles per cell) than
      those of M. galloprovincialis/M. trossulus (60% phagocytosis and 3.5 particles
      per cell). As there is a difference in immune response to contaminants, it is
      suggested that future San Francisco Estuary monitoring should be conducted with
      endemic M. galloprovincialis/M. trossulus rather than with the currently utilized
      M. californianus, which is not found in the estuary.

PMID- 14580809
TI  - Sewage sludge impact on sediment quality and benthic assemblages off the
      Mediterranean coast of Israel-a long-term study.
AB  - The distributions of benthic assemblages, heavy metals and organic carbon (Corg)
      in sediments were examined during a long-term study at a sewage sludge disposal
      site off the Mediterranean coast of Israel. The disposal of sewage sludge has a
      marked but localized, seasonally dependent, impact on the benthic assemblages and
      sediment quality. Elevated concentrations of Corg, Hg, Cd, Cu, Zn, Pb, and to a
      lesser degree Ni in the sediments were detected mostly northward of the sewage
      outfall, in the direction of the prevalent longshore current. High concentrations
      of Corg and metals were reflected by elevated populations of tolerant and
      opportunistic polychaetes in spring and by an azoic zone in fall. The impacted
      area extended mainly towards the north (up to ca. 4 km) and to a lesser extent
      south of the outfall (up to ca. 2.5 km). No evidence of increased accumulation of
      sewage sludge with time was found, nor of pollutants associated with it.
      Principal component analysis (PCA) grouped the anthropogenic metals and Corg with
      infaunal abundance for the spring surveys, while biotic diversity was negatively
      correlated with the pollutants. In the PCA of fall surveys, abundance was
      negatively correlated with the pollutants, decreasing with increased
      concentration of Corg and anthropogenic metals. We suggest that the seasonal
      pattern shown by infaunal abundance, anthropogenic metals and Corg is due to the
      stratification of the water column from spring to fall on one-hand and winter
      storms on the other. Winter storms resuspend and disperse the fine organic
      particles, sweeping the site clean of sludge; accumulation of sludge takes place
      throughout the quiescent periods of the year, when stratification is
      reestablished. The disposal site is dispersive and the spatial extent of the
      impacted area varies seasonally and interannually. This monitoring study, in
      addition to addressing specific questions about sewage sludge impact, represents
      an unusually large and unique set of long-term measurements that will serve as a
      basis to evaluate the site recovery following the cessation of disposal.

PMID- 14580810
TI  - Induction of vitellogenin in vivo and in vitro in the model teleost medaka
      (Oryzias latipes): comparison of gene expression and protein levels.
AB  - Quantification of the egg yolk precursor vitellogenin (VTG) in fish has become a
      standard technique to detect estrogenic effects of known chemicals and
      environmental samples. In the present study, we have analysed VTG induction by
      estradiol, ethynylestradiol and genistein exposure in the model teleost medaka
      (Oryzias latipes) and demonstrate that the medaka is a suitable model system to
      analyse estrogenic effects. By comparing VTG gene expression and protein levels
      we show that in principal both techniques can be used to study VTG induction in
      vivo (juvenile and adult males) and in vitro (primary cultures of male liver
      cells). If a short term in vivo or in vitro exposure is performed, detection of
      mRNA might be sufficient. For long term studies with the need to detect weak
      estrogenic chemicals and a precise quantification, immuno-chemical detection may
      be favoured.

PMID- 14580811
TI  - Fall-related injuries in the elderly in Tehran.
AB  - During 13 months of data gathering, all injury-related information concerning
      trauma patients was gathered according to International Classification of
      Diseases, 10th revision (ICD-10). The severity of the injury was calculated
      according to Abbreviated Injury Scale (AIS-90) in six major university hospitals
      in Tehran. Twelve percent of 8000 hospitalised trauma patients were elderly (65
      years or older) and 70% of them (675 patients) had suffered from fall-related
      injuries. Falling on the ground and falling on stairs were the most common kinds
      of injury (with 462 (68%) and 122 (18%) cases, respectively). In the home and on
      the street were the most common sites of fall occurrence (with 520 cases (77%)
      and 91 cases (13.5%), respectively). After adjustment for the gender, kind of
      fall and Injury Severity Score, it was shown that the elderly were more prone to
      death than their younger counterparts (odds ratio=5.8, 95% CI for odds ratio: 2.3
      7.2), but there was no significant difference in mortality rate between elderly
      men and women. Further studies are needed to evaluate personal and environmental
      risk factors for falls in our population. Furthermore, significantly higher
      mortality rate in our elderly trauma victims necessitates prudent attention to
      elderly trauma care in our teaching hospitals.

PMID- 14580812
TI  - Level of prehospital care and risk of mortality in patients with and without
      severe blunt head injury.
AB  - OBJECTIVES: To determine the association between mortality and the level of
      prehospital care in severely injured blunt trauma patients with or without severe
      head injury. METHOD: Retrospective review of 2010 severe blunt trauma patients
      (injury severity score (ISS) >15) with or without severe head injury in a tiered
      trauma system involving ambulance officers (basic life support (BLS) and advanced
      life support (ALS)) and physicians, and a Level 1 trauma centre. RESULTS: After
      adjusting for age, type of head injury, glasgow coma scale score (GCS), systolic
      blood pressure, ISS and prehospital time, intensive care unit (ICU) admission
      modified the association between level of prehospital care and mortality. In
      those patients without ICU admission, patients in the paramedic and physician
      staffed emergency services group were more likely to die than patients in the BLS
      ambulance group (odds ratio (OR) 2.18, 95% confidence intervals (CI): 1.05-4.55;
      4.27, 95% CI: 1.46-12.45, respectively). Among patients who survived to ICU
      treatment, however, there was no association between level of prehospital care
      and risk of mortality. Presence or absence of a head injury did not modify the
      risk of mortality. CONCLUSIONS: The level of prehospital care was associated with
      the risk of mortality. This was modified by whether the patient survived long
      enough to be admitted to the ICU.

PMID- 14580813
TI  - Pediatric transport related injuries in Tehran: the necessity of implementation
      of injury prevention protocols.
AB  - Prehospital and hospital data was prospectively gathered on all hospitalized
      trauma patients admitted to six major trauma hospitals in Tehran from August 1999
      to September 2000. Data from patients of under 19 years of age was analyzed for
      this article. From 8000 hospitalized trauma patients, 2354 cases (29%) belonged
      to this age group. Fall and transport related injuries (TRIs) with 1074 (46%) and
      921 (39%) cases respectively, were the most common mechanism of injury. In TRIs,
      boys were affected 3.5 times as often as girls. Younger children were more prone
      to pedestrian-related injuries while teenagers were more prone to motorcycle
      related injuries. Head trauma was the most common cause of death and 28 out of 32
      trauma deaths were attributed to this kind of injury. Lower extremity (513) and
      head injuries (322) were the most common injuries. Only a few of motorcyclists
      and car passengers used safety devices (helmet and seat belt respectively) at the
      time of accident.

PMID- 14580814
TI  - Trauma to adult bicyclists: a growing problem in the urban environment.
AB  - The proportion of adults involved in serious bicycle accidents has increased in
      the last two decades. The majority of the bicycle injury prevention efforts,
      however, are directed toward child riders. The authors performed a retrospective
      review of injury statistics from the Massachusetts Hospital Discharge Data Set,
      1994-1999, the Massachusetts Emergency Department Injury Surveillance System,
      1999, and the trauma registry of an Urban Level I Trauma Centre, 1993-2000.
      Massachusetts's state-wide injury data reveals a 30% increase in hospital charges
      between 1994 and 1999 for adults following bicycle falls and collisions with
      concomitant stability in the charges for children. In the years 1993-2000, 60% of
      patients requiring inpatient care at the Study Centre for Bicycle Related
      Injuries were over 16 years of age. Fifty-one percent of patients were without a
      helmet. Positive blood alcohol tests were present in 35 (16%) of the 222
      patients. Forty-six (75%) of patients suffering closed head injury were not
      helmeted. Adult bicycle trauma is a significant health and financial problem in
      the urban state of Massachusetts. Bicycle education and legislation emphasising
      safe bicycling practice, the protective effects of helmets, and the danger of
      cycling under the influence of alcohol may help alleviate this problem.

PMID- 14580815
TI  - The London nail bombings: the St. Thomas' Hospital experience.
AB  - At 18:00 h on 17 April 1999 a nail bomb exploded outside a supermarket in
      Brixton, London. This was the first of a series of three identical nail bombs.
      The injuries were due to penetrating nails, most were relatively minor, with only
      three patients requiring general anaesthesia for removal of nails and
      debridement. One 6-year-old child subsequently underwent onward referral for
      neurosurgical treatment. At 18:40 h on 30 April 1999, the third bomb exploded
      (there were no casualties at our hospital from the second bomb, that in Brick
      Lane on 24 April 1999) in the confined environment of the Admiral Duncan public
      house in Soho. The injuries were much more severe than those seen from the
      Brixton bomb. Two persons died on the scene and 81 were injured; 27 were
      transferred to our hospital. Three primary lower limb amputations were performed.
      Within the first 24h, four patients required ITU care and two onward referral to
      the regional burns unit. Injuries such as those seen in these two bombings are
      common in war situations. In peacetime it is rare to see this spectrum of injury
      and hence surgeons can be unaware of optimal management protocols. Our approach
      in these patients, based on thorough initial debridement and delayed
      closure/split skin grafting is similar to that advocated by the International
      Committee of the Red Cross based on their war surgery experience. We emphasise
      debridement without any initial reconstructive procedures. We also discuss some
      logistic problems of major incidents.

PMID- 14580816
TI  - Have ATLS and national transfer guidelines improved the quality of resuscitation
      and transfer of head-injured patients? A prospective survey from a Regional
      Neurosurgical Unit.
AB  - High-quality resuscitation and care during transfer of head-injured patients is
      essential to prevent secondary brain injury. We have prospectively assessed the
      standard of resuscitation in 50 consecutive head-injured patients transferred to
      our unit, and compared our findings with previous studies performed before the
      advanced trauma life support course (ATLS) had become widespread and national
      guidelines on the transfer of head injuries had been produced by the Association
      of Anaesthetists of Great Britain and Ireland (AAGBI). Delays in transfer,
      management of the airway, adequate cervical spine assessment, hypoxia (P(a)O(2)
      <13 kPa), hypotension (systolic BP <90 mmHg), missed injuries and the experience
      of the medical escort were compared against the standards laid out in ATLS and
      AAGBI Guidelines. The mean, unavoidable delay from arrival at the local accident
      and emergency unit to arrival was 7.4+/-1.9h (mean+/-95%CI) with most of the
      delay being prior to initial referral. Two patients arrived with an unsecured
      airway with a GCS=8/15; 26 had inadequate cervical spine imaging; 7 patients
      arrived hypoxic and 2 patients arrived hypotensive; most of these insults
      occurred during the transfer. Forty-six percent of medical escorts did not fulfil
      the minimum standard of experience. ATLS and AAGBI guidelines have provided only
      modest improvements in patient care at the expense of long delays in transfer.
      The incidence of hypoxia and hypotension remains unacceptably high.

PMID- 14580817
TI  - Reduction of waiting times in A&E following introduction of 'fast-track' scheme
      for elderly patients with hip fractures.
AB  - OBJECTIVE: To investigate the effect of a 'fast-track' scheme (FTS) on waiting
      times in A&E of elderly patients with hip fractures. DESIGN: Retrospective study
      of elderly patients admitted via A&E with a diagnosis of 'hip fracture' between
      May and July 2001. The control group was from the same 3-month period in the year
      before the introduction of the FTS. RESULTS: The reduction in mean waiting times
      between control group (n=61) and study group (n=54) was 3.7h (95% CI: 2.3-5.0 h,
      P<0.001). The two groups also had significantly different variances. However, no
      patient in the 'fast-track' group was transferred to the ward within the 'one
      hour' target set by the UK Audit Commission. CONCLUSIONS: The FTS produced a
      significant reduction in mean waiting times as well as in the variability in
      waiting times for elderly patients with hip fractures.

PMID- 14580818
TI  - The epidemiology of knee and ankle injuries on Macquarie Island.
AB  - Macquarie Island is a small, rugged sub-Antarctic island with a scientific
      research station and a considerable reputation for knee and ankle injuries
      amongst the Australian Antarctic Division expeditioner population. In order to
      examine the accuracy of this reputation, a 10-year retrospective analysis of all
      knee and ankle injuries recorded by the Macquarie Island Medical Officer in the
      medical logs was undertaken. Knee and ankle injuries comprised 13% of the 2,678
      recorded medical consultations. The majority of initial injuries occurred in the
      field and almost a third occurred during work related activities. Ankle ligament
      sprains were the most commonly recorded injury (17%), followed by achilles
      tendonitis (14%), enthesopathy of the knee (16%), and chondromalacia patellae
      (10%). Meniscal tears and collateral ligament of the knee sprains contributed a
      further 11 and 9%, respectively. While there were few significant knee and ankle
      injuries during this period, around a third of the expeditioners represented to
      the Medical Officer with recurrent difficulties.

PMID- 14580819
TI  - A description of events associated with scene response by helicopter based
      medical retrieval teams.
AB  - The critical incident technique, used in critical care related medical
      specialities as a quality tool, may be applicable for evaluation of pre hospital
      care for injured patients. This study describes events documented by medically
      staffed retrieval teams that occurred during a scene response. Incidents were
      defined as events, which may have or did reduce the safety margin for the patient
      and/or retrieval team. Positive events were defined as events that actually did,
      or had the potential to, positively influence the outcome for the patient and/or
      retrieval team task.257 patient transport records had documented events (216
      incidents, 41 positive), 35.6% had multiple events. Doctor's experience
      correlated with event documentation, R(2)=0.614 (P<0.0001). Incidents occurred
      mostly during team dispatch, prior to arrival and whilst team was at the scene.
      Equipment related incidents accounted for 24.3% of incidents. Winch incidents
      accounted for 12% of equipment incidents. Environmental factors were associated
      with 14.3% of incidents. In conclusion, the description of events associated with
      a scene response can be used for quality evaluation. Incidents and positive
      events should be evaluated. Future evaluation can benefit by incorporating
      detailed information from a broader cross-section of retrieval organisations.

PMID- 14580820
TI  - Head injuries: a prospective observational study evaluating the potential impact
      of the Galasko report on Accident and Emergency departments.
AB  - In June 1999, the Galasko report of the Royal College of Surgeons of England
      recommended that in the next 5 years, the Accident and Emergency (A&E)
      departments should admit and supervise head-injured patients for up to 48 h. A
      prospective observational study was carried out for a 6 weeks period at the A&E
      department of Birmingham Heartland's Hospital to identify the potential impact of
      implementation of the Galasko report. The cost implications of this perceived
      additional workload were considered.Of the 786 head-injured patients seen during
      study period, 665 (85%) were discharged home directly from the A&E department. Of
      the remaining 121 patients, who were hospitalized, 76 (63%) were admitted to the
      A&E observation ward (AEOW) and 19 (16%) patients were admitted to a paediatric
      ward. All of these patients were discharged home within 24 h. The remaining 21%
      patients were admitted to other specialities and had prolonged stays in hospital.
      All of the 9% of the patients admitted under orthopaedics would have been
      admitted to the AEOW if the Galasko recommendations were implemented leading to
      an extra 22 bed days over the 6 weeks study period. The estimated annual cost of
      admission alone for these patients would be pound 38,200. Our study has
      demonstrated an expected additional workload and cost implications on a single
      A&E department.

PMID- 14580821
TI  - Quality improvement data analysis of a mass casualty event.
AB  - Trauma auditing is important for monitoring the process of trauma care and
      outcome prediction. This pilot study was conducted to evaluate quality
      improvement (QI) data following a mass casualty event and discuss its impact on
      the trauma care process and outcome. A pre-designed trauma quality improvement
      data set was used for all 103 injured patients admitted to Asir Central Hospital,
      Saudi Arabia, who were involved in a single motor vehicle crash. Most of the
      trauma management variations from norms occurred during the initial assessment
      and resuscitation phase of care, and these had the greatest impact on morbidity
      and mortality. Trauma management variations throughout all phases of care were
      associated with 10% and 9% incidence of preventable morbidity and mortality,
      respectively. Efforts including rigorous educational programs should be made to
      stress the initial assessment and resuscitation phase of care. Successful
      regionalized trauma care systems involving quality improvement programs report
      significant reduction in morbidity and mortality rates from trauma.

PMID- 14580822
TI  - Distal tibiofibular joint dislocation with an intact fibula: a classification
      system.

PMID- 14580823
TI  - Tibialis posterior tendon rupture in children.

PMID- 14580824
TI  - Percutaneous extensor tendon division.

PMID- 14580825
TI  - Irreducible dorsal MTP joint dislocation in the second and third toes.

PMID- 14580826
TI  - Immediate full-weight-bearing mobilisation for repaired Achilles tendon ruptures:
      a pilot study.
AB  - Recent experimental and clinical evidence suggests that early loading and
      mobilisation for Achilles tendon ruptures may improve functional outcomes. This
      paper presents the results of a pilot study designed to assess the safety of
      immediate weight-bearing mobilisation. Twenty-eight operatively repaired patients
      were randomised to either immediate loading in an orthosis or traditional serial
      plaster casting. An independent observer, blinded to treatment, assessed the
      results. Improved clinical, anthropometric, and functional outcomes were noted in
      the immediate loading group. Ultrasound assessment confirmed no deleterious
      effects upon the tenodesis. There was one re-rupture of the tendon at a minimum
      follow-up of 1 year.

PMID- 14580831
TI  - Rasterstereographic back shape analysis in idiopathic scoliosis after posterior
      correction and fusion.
AB  - OBJECTIVE: To determine the accuracy of rasterstereographic three-dimensional
      back surface analysis and reconstruction of the spine in idiopathic scoliosis
      treated by posterior correction and fusion. DESIGN: Prospective imaging study of
      25 patients with idiopathic scoliosis who underwent posterior correction and
      fusion and were followed for one year. BACKGROUND: In an earlier study published
      in this journal rasterstereography has proved to be an accurate imaging modality
      for quantifying the changes in the three-dimensional shape of the spine and
      posterior rib cage after anterior correction and fusion. Goal of the present
      study was to determine the accuracy for the more common posterior correction and
      fusion with attention paid to the presence of the posterior implants and
      scarring. METHODS: Twenty-five patients with idiopathic scoliosis with maximum
      Cobb angles of 78 degrees were examined by rasterstereography and radiography.
      Seventy-one anterior-posterior radiographs were digitised. Twenty-four were
      preoperative and 47 postoperative radiographs. Rasterstereographic and
      radiographic curves were compared by best-fit superimposition. Root-mean-square
      differences were calculated as parameters of accuracy. RESULTS: The accuracy of
      rasterstereography in severe idiopathic scoliosis with Cobb angles between 48
      degrees and 78 degrees was satisfactory with root-mean-square differences of 5.8
      mm for the lateral deviation and 4.8 degrees for vertebral rotation. Following
      posterior correction the accuracy was good. The root-mean-square difference was
      4.5 mm for the lateral deviation and 4.3 degrees for vertebral rotation.
      CONCLUSION: The accuracy obtained for posteriorly-operated scolioses between 50
      degrees and 80 degrees was similar to the findings for scolioses operated via
      anterior approach, as well as those with curves up to 50 degrees Cobb angle.
      Therefore rasterstereography can be used postoperatively to reduce the number of
      radiographs and radiation exposure. Additionally, the method provides an
      objective quantification of the postoperative improvement in the cosmesis of the
      back shape. RELEVANCE: In the treatment of severe idiopathic scoliosis
      rasterstereography provides both a considerable reduction of X-rays and an
      objective documentation of the cosmesis before after scoliosis surgery.

PMID- 14580832
TI  - Biomechanics and electromyography of a cumulative lumbar disorder: response to
      static flexion.
AB  - OBJECTIVE: To assess the mechanical and neurological processes active in the
      development of a cumulative trauma disorder (CTD) associated with repetitive
      exposure to periods of static lumbar flexion. METHODS: The spine of the feline
      model was subjected to a series of three 10 min sessions of static lumbar flexion
      with each session followed by a 10 min rest. A 7 h rest period was implemented
      after the series of three flexion-rest sessions while monitoring viscoelastic
      (disks, ligaments, etc.) creep and multifidus EMG. A model was fitted to the
      experimental data from the flexion-rest period and the 7 h recovery period.
      RESULTS: The creep developed in each 10 min static flexion period did not fully
      recovery during the following 10 min rest, resulting in a large cumulative creep
      at the end of the flexion-rest period. The cumulative creep did not fully recover
      over the following 7 h rest period. A neuromuscular disorder consisting of
      reduced muscular activity superimposed by spasms during static flexion periods
      and hyperexcitability during the 7 h recovery was evident. Comparison of the data
      to previous tests of continuous static flexion for 20 min reveal that the
      neuromuscular disorder elicited by the series of three 10 min flexion-rest was
      substantially attenuated when compared to a single 20 min static flexion although
      the overall work time was 50% larger. CONCLUSIONS: Frequent rest periods are
      highly beneficial in attenuating the development of a CTD, yet not able to
      prevent it, as viscoelastic tissues residual creep accumulates and its recovery
      is of extremely long duration. RELEVANCE: The data provides direct biomechanical
      and physiological evidence that explain the development of a CTD due to prolonged
      exposure to static lumbar flexion as well as confirms the epidemiological data
      correlating such work conditions with substantial increase in symptoms of low
      back disorders. The benefit of frequent rest periods in attenuating the risk of
      such a disorder is validated as an effective intervention.

PMID- 14580833
TI  - Quantitative in vivo studies of median nerve sliding in response to wrist, elbow,
      shoulder and neck movements.
AB  - OBJECTIVE: To examine median nerve sliding in response to upper limb movements in
      vivo. To determine whether the median nerve can be unloaded. DESIGN: Exploratory
      study in healthy subjects.Background. Impaired sliding may lead to neuropathic
      symptoms. In vivo results for neural dynamics in normal subjects are essential to
      understand changes in upper limb disorders. METHODS: Ultrasound imaging of the
      median nerve during 40 degrees wrist extension, 80 degrees shoulder abduction, 90
      degrees elbow extension, and 35 degrees contralateral neck side flexion. Frame by
      frame cross-correlation of image sequences to measure nerve sliding and strain.
      RESULTS: Nerve excursion in the forearm and upper arm ranged from 0.3 mm for neck
      side flexion to 10.4 mm for elbow extension. Additional strain in the forearm for
      wrist extension was 1.1% (SEM, 0.2%), for shoulder abduction 1.0% (SEM, 0.2%),
      and for neck side flexion 0.1% (SEM, 0.1%). With the limb flexed, sliding was
      delayed and sometimes the nerve or the nerve fascicles had a wavy appearance.
      CONCLUSION: The median nerve is unloaded when the shoulder is adducted or elbow
      flexed. When the arm is extended (90 degrees shoulder abduction, 60 degrees wrist
      extension, and elbow straight) the total additional strain in the forearm will be
      2.5-3.0%. Even in this position the strain is likely to be below levels that
      impair blood flow or conduction. Therefore, the median nerve appears well
      designed to cope with changes in bed length caused by limb movements. RELEVANCE:
      These results will provide baseline data that can be used to examine entrapment
      neuropathies.

PMID- 14580834
TI  - Multi-directional strength and force envelope of the index finger.
AB  - OBJECTIVE: The purpose of this study was to biomechanically evaluate the motor
      function of the index finger based on multi-directional strengths. DESIGN: An
      experimental apparatus was developed to measure force production of a digit at
      various points of force application along the digit and in any direction of force
      application within the transverse plane of the longitudinal axis of the digit.
      BACKGROUND: Most existing tests of hand motor function are subjective,
      semiquantitative, and/or non-specific. METHODS: Eight normal subjects with
      asymptomatic hands were tested. Maximum voluntary isometric contraction forces
      were measured at the middle of the proximal phalanx of the index finger in 16
      directions that were evenly distributed within 360 degrees. RESULTS: The highest
      force, 110.7 (SD 9.0) N, was generated in flexion, while the lowest force was
      generated in extension. The forces in extension, abduction and adduction were
      37.6%, 97.9% and 79.3% of the flexion force, respectively. The area of the force
      envelope was 25739 (SD 3688) N-N. The average percentage quadrant areas, relative
      to the total force envelope area, for extension-adduction, extension-abduction,
      flexion-abduction, and flexion-adduction were 12.9%, 20.4%, 36.0%, and 30.8%,
      respectively. The average percentage quadrant areas for extension, abduction,
      flexion, and adduction were 9.1%, 33.3%, 35.6%, and 22.1%, respectively.
      CONCLUSION: The current study provides an advanced level of quantification of
      hand motor function. RELEVANCE: The methods may be used as a basis to detect
      changes in the motor function resulting from pathological conditions, disease
      progression, as well as rehabilitation and treatment of these disorders.

PMID- 14580835
TI  - Influence of preoperative mechanical bone quality and bone mineral density on
      aseptic loosening of total hip arthroplasty after seven years.
AB  - OBJECTIVE: To test mechanical bone quality and bone mineral density of the
      femoral head at the day of implantation as indicators for femoral prosthesis
      loosening. METHODS: Mechanical bone quality of a femoral head slice was assessed
      by destructive compression testing combined with bone mineral density
      measurements using peripheral quantitative computed tomography. Fourteen patients
      with walking pains were attainable for a radiographical follow-up mean 7.1 years
      after implantation. RESULTS: Radiolucent lines along the stem were evident in 11
      of 14 femurs, most of them seen in Gruen zones 7, 6, 1, 3, 14, and showed strong
      correlations to preoperative bone strength (r=-0.80; P<0.001) and axial stiffness
      (r=-0.75; P=0.002), yet not to bone mineral density (r=-0.67; P=0.009). Slight
      varus deviations <3 degrees were noted in six femurs. Preoperative strength was
      reduced in this femurs to 54% (P=0.006), and stiffness to 61% (P=0.038), while
      bone mineral density did not differ significantly. CONCLUSIONS: Femoral
      prosthesis loosening after seven years can be predicted by mechanical bone
      quality of the femoral head at the time of implantation. Bone mineral density
      measurements may also indicate future stem loosening but have to interpreted
      carefully, keeping in mind a poorer predictive value. RELEVANCE: Indications and
      choice of type of hip arthroplasty should be balanced in osteoporotic bones in
      particular. While preoperative bone mineral density measurement allows the
      prediction of mechanical bone quality, its relevance in predicting failure in
      arthroplasty treatment remains unclear.

PMID- 14580836
TI  - Three-dimensional morphometry of the femoral condyles.
AB  - OBJECTIVE: The present study describes the geometry of the three-dimensional
      articular surfaces of the human femoral condyles based on measurements of surface
      coordinates. DESIGN: The purpose was not to obtain a complex representation of
      one single condyle, but to describe the femoral condyles using simple geometric
      parameters based on measurements using a number of specimens. BACKGROUND: In
      joint modeling, a representative knee joint geometry is often desired which
      requires an approximation of the irregular joint geometry while taking into
      account interspecimen variations. METHODS: An optical device was used to measure
      the condylar articular surfaces of 12 human femurs in the femorotibial contact
      region. The sagittal profiles were reconstructed by means of two circular arcs
      and the radial profiles by means of one circular arc. RESULTS: The results
      provide the geometric parameters necessary for the three-dimensional
      reconstruction of the articular surfaces of the femoral condyles. The results
      indicate that the medial and lateral condyles of the distal femur are
      significantly asymmetric in a number of morphological features. CONCLUSION: The
      primary application of the results is expected to be in the formulation of finite
      element models of the knee joint for static contact problems. RELEVANCE:
      Numerical models of the knee joint are being widely used to study the mechanics
      of the joint. However, formulation of such models demands a prior knowledge of
      the complex three-dimensional geometry of the articular surfaces of the natural
      joint to establish the input parameters of the model.

PMID- 14580837
TI  - Modeling of ACL impingement against the intercondylar notch.
AB  - OBJECTIVE: To develop a 3-D mathematical model that accurately evaluates anterior
      cruciate ligament impingement against the intercondylar notch. DESIGN: The model
      simulated physical interactions between the anterior cruciate ligament and the
      intercondylar notch in tibiofemoral movement. BACKGROUND: Anterior cruciate
      ligament impingement has been evaluated through planar radiographic images, which
      may not characterize the complex 3-D notch shape associated with impingement.
      METHODS: After examining potential anterior cruciate ligament impingement in five
      cadaver knee specimens, the model was implemented using data from an individual
      cadaveric knee with representative impingement. The knee was loaded passively in
      various patterns to induce impingement, and the impingement force and six degrees
      of-freedom tibiofemoral kinematics were measured. The femur, tibia, and anterior
      cruciate ligament were digitized. Spatial data points representing the notch
      surfaces were surface-fitted using bicubic splines. The model detected for
      impingement during the tibiofemoral movement and used a "crawling algorithm" to
      determine the deformed geometry of the impinging ligament. RESULTS: The model
      detected the impingement accurately and the ligament strain determined by the
      model was highly correlated with the recorded impingement force when impingement
      occurred during the tibiofemoral movement. Distance between the anterior cruciate
      ligament and the notch wall was determined when impingement was not detected.
      CONCLUSION: The model quantitatively characterized impingement of the anterior
      cruciate ligament against the intercondylar notch in 3-D space. RELEVANCE: The
      approach helps us better understand anterior cruciate ligament injury mechanisms
      in individual knees. Clinically, the model could potentially be used to analyze
      subject-specific potential/actual anterior cruciate ligament impingement based on
      the subject's MRI scans.

PMID- 14580838
TI  - Biomechanical evaluation of a newly devised model for the elongation-type
      anterior cruciate ligament injury with partial laceration and permanent
      elongation.
AB  - OBJECTIVE: To biomechanically evaluate a newly devised model for the elongation
      type anterior cruciate ligament injury with partial laceration and permanent
      elongation. DESIGN: Thirty-six rabbits were randomly divided into 4 groups of 9
      animals each, after a quantitative injury was given to the right anterior
      cruciate ligament. The 4 groups were sacrificed at 0, 6, 12, and 24 weeks after
      surgery, respectively. Biomechanical and histological evaluations were performed
      at each period. BACKGROUND: No adequate animal models have been established for
      the elongation-type anterior cruciate ligament injury in which the mid-substance
      is permanently elongated with partial laceration. METHODS: The anteromedial and
      posterolateral half of the anterior cruciate ligament was transected at the
      proximal and distal one-third levels, respectively. Then, the anterior cruciate
      ligament was stretched by applying an anterior drawer force to the tibia at 90
      degrees of knee flexion. RESULTS: The treatment significantly increased the
      anterior translation of the knee into approximately 150-250% at each period after
      surgery. The maximum load and the stiffness of the femur-anterior cruciate
      ligament-tibia complex significantly decreased to 30% or less immediately after
      surgery, and then gradually increased to 50% at 12 weeks. CONCLUSIONS: In this
      model, this quantitative treatment created serious injuries with partial
      laceration and permanent elongation in the anterior cruciate ligament to similar
      degrees. Also, incomplete tissue healing occurred in the anterior cruciate
      ligament to similar degrees after the treatment. RELEVANCE: This model will be
      useful to study new therapeutic methods for the elongation-type anterior cruciate
      ligament injury.

PMID- 14580839
TI  - Frontal and sagittal plane analyses of the stair climbing task in healthy adults
      aged over 40 years: what are the challenges compared to level walking?
AB  - OBJECTIVE: This study compared stair climbing and level walking in healthy adults
      aged over 40 years. DESIGN: Eleven subjects performed at their comfortable speed.
      BACKGROUND: The number of parameters studied during stair climbing has been
      limited, in particular in the frontal plane. METHODS: Time-distance parameters
      and three-dimensional kinematic data were obtained using foot-switches and an
      Optotrak system. Ground reaction forces were collected with a force platform
      embedded in the second step of the staircase or in the ground for level walking.
      Relative angles were calculated using a Cardanic rotation matrix and the net
      moments and the powers at the ankle, knee and hip joints were estimated with an
      inverse dynamic approach. RESULTS: A significant longer mean cycle duration and a
      shorter proportion of time in stance was obtained for stair climbing as compared
      to level walking. Profiles of the frontal plane joint angles, moments and powers
      indicated a different action of the hip abductors across tasks to control the
      pelvis in stance. Profiles of the sagittal plane confirmed the dominant role of
      the knee extensors during stair climbing but revealed also a knee-hip energy
      generation pattern that allows the avoidance of the intermediate step.
      CONCLUSIONS: Results suggest environment specific adaptations of the neuro
      musculo-skeletal system that should be considered in the rehabilitation of stair
      climbing in patients. RELEVANCE: This study highlights the challenges of stair
      climbing compared to level walking in a within subject design. Key features of
      stair climbing that are important for the rehabilitation of step management are
      also reported.

PMID- 14580840
TI  - Propagation of surface fissures in articular cartilage in response to cyclic
      loading in vitro.
AB  - BACKGROUND: Mechanical overloading of synovial joints can damage the articular
      cartilage surface and may lead to osteoarthritis. However, causal links between
      mechanical and biological events in cartilage are poorly understood. OBJECTIVES:
      To test the hypothesis that surface fissures in cartilage can propagate
      mechanically if the joint surface is subjected to vigorous cyclic loading.
      METHODS: Thirty-five cartilage-on-bone specimens, 15-mm square, were removed from
      mature bovine knee and shoulder joints. Specimens were loaded by means of a 9-mm
      diameter flat indenter with a beveled edge, and their compressive strength
      determined. Failure occurred in the cartilage surface at an average stress of 36
      MPa. Cartilage fissures were marked with Indian ink, photographed, and their
      length and width measured using image analysis software. Each damaged specimen
      was subjected to cyclic loading at 40% of its compressive strength, at 0.5 Hz,
      for up to 5 h. Fissure length and width were measured at regular intervals. After
      testing, fissure depth was measured from histological sections, and compared with
      measurements from damaged cartilage which was not cyclically loaded. RESULTS:
      Cyclic loading caused cartilage fissures to increase in length (mean 353%,
      P<0.01) and width (360%, P<0.01) but not depth. Propagation was rapid at first,
      but approached equilibrium after several hundred cycles. Rehydration in saline
      had no effect on fissure length, but width returned to pre-cyclic loading values.
      CONCLUSION: Cartilage fissures can propagate mechanically when a joint surface is
      subjected to cyclic compressive loading in vitro. The transient opening-up of
      fissures to form wide surface "wounds" during cyclic loading could be of
      biological significance if it occurred in living people. RELEVANCE: In living
      joints, wide open fissures in the cartilage surface could promote degenerative
      changes in the tissue.

PMID- 14580841
TI  - Mechanical response of tendon subsequent to ramp loading to varying strain
      limits.
AB  - OBJECTIVE: To determine the in vitro elastic limit of avian flexor tendons
      utilizing more current methodologies. DESIGN: Assess the mechanical changes
      between subfailure and subsequent failure ramps at various loading levels.
      BACKGROUND: Currently accepted values of elastic strain limits were determined
      utilizing older methodologies. Consequently, reported values are fairly small and
      imply matrix damage occurs with small strains. METHODS: Flexor tendons were
      loaded in vitro, to various subfailure strain levels between 1% and 14%, allowed
      to rest for 5 min, then taken to failure. Suture markers, across the
      midsubstance, and cryo-grip displacement were monitored for strain using a video
      strain analysis system and a linear variable displacement transducer,
      respectively. The mechanical changes between the various subfailure and failure
      ramp loadings were assessed. RESULTS: Varying strains of subfailure ramp loading
      did not influence (P>0.05) the ultimate tensile failure strength, elastic
      modulus, strain at failure, or strain energy density of tendons. In addition,
      residual strain after subfailure loading was not significant, nor was it
      influenced by the level of the subfailure loading. CONCLUSIONS: Tendon behaves
      elastically under ramp loading to significantly higher strains (nearly failure)
      than previously reported (4%). RELEVANCE: This study has found strain thresholds
      required to cause matrix damage to be significantly higher than previously
      thought, implying that matrix changes to acute loading events are more a result
      of the cellular response to the loading event. The clinical relevance is that the
      clinician may have a greater opportunity to prevent matrix changes than once
      thought by biochemically altering the cellular response.

PMID- 14580842
TI  - A new method for cerclage wire fixation to maximal pre-tension with minimal
      elongation to failure.
AB  - OBJECTIVE: To develop and test a new cerclage wire tightening technique, yielding
      reproducibly maximal pre-tension, load to failure and minimal elongation to
      failure of the wire junction. DESIGN: Laboratory bench study. BACKGROUND:
      Cerclage wire fixation is difficult to perform by hand with reproducible quality
      and tightening tension, which are required for optimal performance. METHODS: With
      the new technique, 1, 1.25 and 1.5 mm steel wires were passed through a 9 x 18 mm
      steel tube, grasped using a modified ASIF wire-tightener and tightened by
      twisting until spontaneous failure of the wires in the tube. These fixations were
      compared to wires pre-tightened by hand to controlled high or low pre-tension
      using the simple twist, the knot twist and twist secured against untwisting,
      loaded to failure on a testing machine. The tests assessed pre-tension, ultimate
      failure load and elongation to failure. RESULTS: Wire twists performed with the
      new technique were always perfectly symmetrical and may be tightened to maximal
      pre-tension without weakening of the wire. The twist secured against untwisting
      combined high stiffness with high failure load. The knot twist elongates to an
      unacceptable degree, unlike the secured twist. The simple twist untwists under
      little tension. CONCLUSIONS: The new technique allows to obtain maximal pre
      tension and thus minimal elongation to failure of simple wire twists, without
      having to worry about breaking the wire at the base of the twist due to over
      tightening. RELEVANCE: Cerclage wire fixation is an effective and cheap method to
      perform osteosynthesis. For adequate performance, maximal pre-tension,
      symmetrical twisting and high load to failure are necessary. The here presented
      technique combines all of these pre-requisites in a simple fashion.

PMID- 14580843
TI  - System to monitor task chair seating.
AB  - OBJECTIVE: To record chair data such as seat occupancy, back recline angle,
      lumbar engagement, and armrest location using an independent, unbiased real time
      data acquisition system. DESIGN: The system should be inconspicuous. The users
      should be able to work effectively in their environment oblivious to concurrent
      data collection. BACKGROUND: While human acquisition and measurement instruments
      provide an acceptable approach for collecting data on changing chair positions,
      they may bias data. Current data collection methods such as video playback can
      also be successful in collecting chair data, but are often time-consuming and
      expensive to set up. METHODS: Four key areas were concentrated upon for
      monitoring: seat, lumbar, back recline, and armrest position. A position switch
      was mounted to each locale and linked to a microprocessor to track the changing
      positions of the chair in real time. RESULTS: The chair provides time stamped
      data on the changes that take place to the chair. The data can be downloaded at
      the convenience of the user and researcher. CONCLUSIONS: The chair is complete
      and ready for data acquisition. It permits easy data collection on chair
      positions without hindering the user's movement. RELEVANCE: This tool provides an
      automated, independent method for collecting data on chair positions. Information
      can be collected and studies conducted on seated durations, chair back motion
      while seated, chair lumbar usage, and common armrest location while in a visual
      display terminal workstation.

PMID- 14580844
TI  - Impact of high pressure freezing on DH5alpha Escherichia coli and red blood
      cells.
AB  - The impact of high pressure and freezing on survivability of Escherichia coli and
      human red blood cells was evaluated to determine the utility of high-pressure
      transitions for preserving living cells. Based on microscopy and survivability,
      high pressures did not directly impact physical damage to living cells. E. coli
      studies showed that increased cell death is due to indirect phenomena with
      decreasing survivability at increasingly high pressures and exposure times.
      Pressurization rates up to 1.4kbar/min had negligible effects relative to
      exposures of >5min at high pressures.Both glycine and control of pH near 7.0 were
      successful in reducing the adverse impacts of high pressure. Survivability
      increased from <1% at 5min exposure to 2.1kbar of pressure to typical values
      >20%. The combination of glycine and the buffer salt led to even further
      improvements in survivability. Pressure changes were used to traverse temperature
      and pressures consistent with Ice I and Ice III phase boundaries of pure water.

PMID- 14580845
TI  - Effects of cooling ovaries before oocyte aspiration on meiotic competence of
      porcine oocytes and of exposing in vitro matured oocytes to ambient temperature
      on in vitro fertilization and development of the oocytes.
AB  - Experiments were conducted to evaluate the effects of cooling porcine ovaries to
      low temperature (4 degrees C, 15 degrees C, 20 degrees C, 25 degrees C or 30
      degrees C) for 1 h on the meiotic competence of their oocytes. Moreover, it was
      determined whether or not the exposure of in vitro matured oocytes to ambient
      temperature (20 degrees C, 25 degrees C or 30 degrees C) for 1 h affects the
      fertilization and developmental competence of the oocytes. There was no
      difference between the proportions of oocytes that underwent maturation to
      metaphase II when isolated from control ovaries held at 35 degrees C and ovaries
      exposed to 30 degrees C. However, the percentages of oocytes from ovaries exposed
      to 25 degrees C or less were significantly lower than those of oocytes from
      ovaries exposed to 30 degrees C and control ovaries. The proportions of total and
      normal fertilization of oocytes that had been exposed to 20 degrees C before in
      vitro fertilization (IVF) were significantly lower than those of control oocytes
      maintained at 38.5 degrees C. However, cooling in vitro matured oocytes had no
      effects on their cleavage and development to blastocysts after IVF. These data
      suggest that exposing porcine ovaries to a low temperature of 25 degrees C or
      less before aspiration of oocytes may adversely affect their subsequent in vitro
      maturation. It may be necessary to maintain the oocytes at a temperature of more
      than 25 degrees C during manipulation of oocytes for retaining the
      fertilizability of the oocytes.

PMID- 14580846
TI  - Cryopreservation of canine spermatozoa: theoretical prediction of optimal cooling
      rates in the presence and absence of cryoprotective agents.
AB  - In the present study a shape independent differential scanning calorimeter (DSC)
      technique was used to measure the dehydration response during freezing of
      ejaculated canine sperm cells. Volumetric shrinkage during freezing of canine
      sperm cell suspensions was obtained at cooling rates of 5 and 10 degrees C/min in
      the presence of extracellular ice and CPAs (6 different combinations of freezing
      media were used, ranging from a media with no CPAs, and those with 0.5%, 3%, and
      6% glycerol and with 0.5% and 3% Me(2)SO). Using previously published data, the
      canine sperm cell was modeled as a cylinder of length 105.7mum and a radius of
      0.32mum with an osmotically inactive cell volume, V(b), of 0.6 V(o), where V(o)
      is the isotonic cell volume. By fitting a model of water transport to the
      experimentally obtained volumetric shrinkage data the best fit membrane
      permeability parameters (L(pg) and E(Lp)) were determined. The "combined best
      fit" membrane permeability parameters at 5 and 10 degrees C/min for canine sperm
      cells in the absence of CPAs are: L(pg)=0.52x10(-15)m(3)/Ns (0.0029mum/min-atm)
      and E(Lp)=64.0kJ/mol (15.3kcal/mol) (R(2)=0.99); and the corresponding parameters
      in the presence of CPAs ranged from L(pg)[cpa]=0.46 to 0.53x10(-15) m(3)/Ns
      (0.0027-0.0031mum/min-atm) and E(Lp)[cpa]=46.4-56.0kJ/mol (11.1-13.4kcal/mol).
      These parameters are significantly different than previously published parameters
      for canine and other mammalian sperm obtained at suprazero temperatures and at
      subzero temperatures in the absence of extracellular ice. The parameters obtained
      in this study also suggest that optimal rates of freezing canine sperm cells
      ranges from 10 to 30 degrees C/min; these theoretical cooling rates are found to
      be in close conformity with previously published but empirically determined
      optimal cooling rates.

PMID- 14580847
TI  - Detection of mitochondrial electron chain carrier redox status by transhepatic
      light intensity during rat liver reperfusion.
AB  - The aim of the study was to investigate mitochondrial electron transfer during
      rat liver reperfusion after cold storage and hypothermic machine perfusion.
      Livers from male Brown Norway rats were preserved (UW) for 10h either by cold
      storage (CS) or by hypothermic oxygenated perfusion extracorporal (HOPE).
      Transhepatic photometric analysis allowed determination of the redox status of
      mitochondrial cytochromes during preservation, rewarming and reperfusion.
      Mitochondrial electron chain carriers were inhibited at different sites with
      rotenone and cyanide in some experiments. reversed transcriptional polymerase
      chain reaction (RT-PCR) was performed after reperfusion concerning transcription
      of TNFalpha, caspase 9, and c-jun kinase (JNK). Increased superoxide anion
      formation as well as transcription of TNFalpha, caspase 9, and JNK during
      reperfusion after cold storage (CS) were related with completely reduced
      cytochromes before and during reperfusion. In contrast, hypothermic oxygenated
      livers (HOPE) showed oxygenated cytochromes as well as decreased superoxide anion
      formation and no detectable transcription of TNFalpha, caspase 9, and JNK. A
      similar low level of superoxide anion formation was found when electron chain
      transfer of cold stored livers was inhibited during reperfusion with rotenone but
      not with cyanide. After hypothermic oxygenation (HOPE) inhibition of
      mitochondrial electron chain with rotenone showed no change in formation of
      superoxide anion formation whereas inhibition with cyanide showed increased
      superoxide anion formation. Thus mitochondrial cytochrome redox status is
      suggested to be related: (i) with the release of reactive oxygen substances as
      well as (ii) with the expressions of TNFalpha, caspase 9, and JNK during
      reperfusion and may thus be usable as predictive marker of liver grafts.

PMID- 14580848
TI  - A microscale model for prediction of breast cancer cell damage during
      cryosurgery.
AB  - The morphology of cancerous breast tissue is characterized by tightly packed
      groups of small malignant cells, as found in most duct cell carcinoma. This
      special structure affects the osmotic responses of the cells to freezing and
      hence their probability of damage from cellular dehydration or intracellular ice
      formation. A mathematical model has been developed to study the microscale damage
      to these breast cancer cells during cryosurgery by accounting for their special
      structure. The model is based on a spherical unit comprised of an extracellular
      region that surrounds several layers of cancer cells, as experimentally observed
      of breast duct cell carcinoma by other researchers. Temperature transients in the
      breast cancer undergoing cryosurgery are calculated numerically using the Pennes
      equation. When subjected to various thermal histories, both cellular dehydration
      and intracellular ice formation in the unit structure are examined by considering
      the cell-to-cell contact and water transport at the microscale level. It is found
      that the cells in the inner layers hardly dehydrated while those in the outermost
      layer do greatly. The results help interpret the previously observed experimental
      phenomena that breast cancer tissues exhibit intracellular ice formation even at
      a slow cooling rate of -3 degrees C/min. In the attempt to better define an
      optimal procedure for breast cancer cryosurgery, various freezing protocols are
      simulated. The constant heat flux protocol induces greater cellular dehydration
      and higher intracellular ice formation probability simultaneously compared to the
      other protocols studied.

PMID- 14580849
TI  - Screening of genes that respond to cryopreservation stress using yeast DNA
      microarray.
AB  - We studied the response of yeast cells after cryopreservation treatment using DNA
      microarray technology. Genes that contribute to "Cell rescue, defense and
      virulence," "energy," and "metabolism," were significantly induced. These genes
      were classified as encoding heat shock proteins, oxidative stress scavenger, and
      enzymes involved in glucose metabolism. The expression profile of mRNA after
      cryopreservation treatment was calculated to be closer to that following
      treatment with detergent or plant oils rather than by other stress factors such
      as heavy metals and agricultural chemicals. These results suggest that the
      cryopreservation treatment caused damage to the structure of the cell wall and
      cellular organelles. This was supported by the localization of the products of
      the induced genes at the cell wall and within cellular organelles.

PMID- 14580850
TI  - Hepatic cold hypoxia and oxidative stress: implications for ICAM-1 expression and
      modulation by glutathione during experimental isolated liver preservation.
AB  - Cold preservation and reperfusion of liver during transplantation are necessary
      steps in the procedure but which are also associated with damage to the organ.
      One aspect of this damage is thought to concern up-regulation of inflammatory
      markers, such as the adhesion molecule intercellular adhesion molecule 1 (ICAM-1)
      on target cells in the liver. This aids sequestration of activated leucocytes,
      which promote inflammation, by a complex sequence of events, including free
      radical mediated damage. We have studied changes in ICAM-1 in rat liver as a
      consequence of cold preservation for various times, and also after warm
      reperfusion during isolated liver perfusion. We have also investigated the
      effects of the free radical scavenging agent (reduced glutathione-GSH) on the
      modulation of ICAM-1 expression after cold hypoxia and reperfusion. Livers were
      subjected to various regimes of cold preservation and reperfusion. Liver biopsies
      were taken at three time points (initial baseline on liver exposure; after organ
      flushing and post-storage at 0, 8, 16, and 24h cold hypoxia in University of
      Wisconsin solution; in the same livers after 1h warm reperfusion). The tissues
      were processed for frozen biopsy work, and frozen sections were stained using
      immunohistochemical methods, for blinded scoring by an independent observer.
      Positive controls were obtained by exposure to endotoxin lipopolysaccharide
      before liver flushing. ICAM-1 expression was low in control livers (0.33+/-0.21),
      and increased to near maximal (2.83+/-0.17) after endotoxin exposure. ICAM-1
      expression increased progressively with cold preservation, reaching values of
      1.17+/-0.31 and 1.83+/-0.31 after 16 and 24h, respectively (P<0.05 and 0.02
      versus controls). Warm reperfusuion increased ICAM-1 expression in all flushed
      groups and with longer cold preservation was close to maximal (2.67+/-0.21 after
      16h and 2.98+/-0.02 after 24h; P<0.001 in both cases). Addition of the free
      radical scavenger GSH prevented up-regulation of ICAM-1 in livers reperfused
      after flushing and cold storage for up to 8h; beyond this time, ICAM-1 expression
      still increased, such that by 24h cold preservation and reperfusion absence
      (2.98+/-0.02) or presence (2.67+/-0.21) made no difference. We conclude that
      liver ICAM-1 expression is demonstrably increased by progressive cold
      preservation and reperfusion, and is only marginally affected by addition of GSH
      during reperfusion. The model can be used to investigate other agents which might
      be more successful in preventing post-storage inflammatory damage.

PMID- 14580851
TI  - Sequelae of cryotherapy in breast tissue.
AB  - Cryotherapy is a novel treatment for benign and malignant breast lesions that is
      under evaluation. We assessed the acute and subacute outcomes of breast
      cryotherapy in normal goat teats using physical, microscopic, and imaging
      modalities. Eight goats were subjected to two freeze-thaw cycles of breast tissue
      producing a 2cm iceball and sacrificed either 2 or 7 weeks later. Acute skin
      changes were minimal unless obvious tissue injury occurred during cryotherapy;
      however, depigmentation developed over several weeks in dark-skinned goats
      despite the presence of melanocytes. By histology, breast epithelial elements
      could not be identified at cryotherapy sites. There was no cystic degeneration,
      which is common at surgical excision sites. Neither calcifications nor prominent
      scarring could be attributed to cryotherapy on imaging studies after 2 or 7
      weeks. When compared to standard breast surgery, the sequelae of cryotherapy
      using histologic, radiographic, and sonographic criteria were decreased. Our
      study suggests that cryotherapy, with technical modifications, is feasible within
      breast tissue and warrants further study.

PMID- 14580852
TI  - Cryopreservation of human brain tissue allowing timely production of viable adult
      human brain cells for autologous transplantation.
AB  - BACKGROUND: Autologous transplantation is an attractive approach to treat some
      neurological diseases. A major obstacle is the capacity to produce cells for
      transplantation at the appropriate time. We describe a cryopreservation procedure
      for adult human brain tissue allowing the generation of cells in vitro. METHODS:
      Neurological resections were dissected to separate white and grey matter.
      Fractions were frozen in a specific cryopreservation medium containing a selected
      serum and stored in liquid nitrogen. Tissue was thawed, cells were mechanically
      dissociated, expanded in culture and characterized by immunochemistry. RESULTS:
      Adult human brain tissue cryopreserved for up to two years was successfully used
      to generate brain cells that could be maintained in culture for up to 100 days.
      Cells expressed a variety of neuroectodermal markers including GFAP, S100beta,
      and neurofilament. CONCLUSION: A successful procedure for cryopreservation of
      adult human brain tissue has been established that might facilitate future
      autologous transplantation strategies.

PMID- 14580853
TI  - Influence of cryoprotective agent and cooling rate on frozen and thawed hemocytes
      from the Mollusk Haliotis tuberculata.
AB  - Cultures of circulating cells from abalone (Haliotis tuberculata) may be used in
      fundamental research or in biotechnology. This paper describes attempts to
      develop a cryoconservation method for these hemocytes in order to constitute a
      standardized cell stock. Among a panel of five distinct cryoprotective solutions,
      10% v/v glycerol ('G solution') was the most effective and better post-thaw
      recovery was achieved after cooling at 1 degrees C/min than after more rapid
      cooling (3 degrees C or 9 degrees C/min). In 2-day-old cultures, cell viability,
      assessed by DNA or protein content, was 83 and 78%, respectively, and metabolic
      activity, measured by the MTT reduction assay, reached 96%. Viability rates were
      only slightly reduced after 6 days of culture, suggesting a low proportion of
      damaged cells among the surviving hemocytes. This study identified a
      cryoprotective solution and a freezing protocol that allow thawed hemocytes to
      recover a large part of their viability.

PMID- 14580854
TI  - The necessity of chance: would elimination of aging suppress evolution?

PMID- 14580855
TI  - New trends in bioinformatics: from genome sequence to personalized medicine.
AB  - Molecular medicine requires the integration and analysis of genomic, molecular,
      cellular, as well as clinical data and it thus offers a remarkable set of
      challenges to bioinformatics. Bioinformatics nowadays has an essential role both,
      in deciphering genomic, transcriptomic, and proteomic data generated by high
      throughput experimental technologies, and in organizing information gathered from
      traditional biology and medicine. The evolution of bioinformatics, which started
      with sequence analysis and has led to high-throughput whole genome or
      transcriptome annotation today, is now going to be directed towards recently
      emerging areas of integrative and translational genomics, and ultimately
      personalized medicine.Therefore considerable efforts are required to provide the
      necessary infrastructure for high-performance computing, sophisticated
      algorithms, advanced data management capabilities, and-most importantly-well
      trained and educated personnel to design, maintain and use these environments.
      This review outlines the most promising trends in bioinformatics, which may play
      a major role in the pursuit of future biological discoveries and medical
      applications.

PMID- 14580856
TI  - Aging and molecular chaperones.
AB  - Chaperone function plays a key role in sequestering damaged proteins and in
      repairing proteotoxic damage. Chaperones are induced by environmental stress and
      are called as stress or heat shock proteins. Here, we summarize the current
      knowledge about protein damage in aged organisms, about changes in proteolytic
      degradation, chaperone expression and function in the aging process, as well as
      the involvement of chaperones in longevity and cellular senescence. The role of
      chaperones in aging diseases, such as in Alzheimer's disease, Parkinson's
      disease, Huntington's disease and in other neurodegenerative diseases as well as
      in atherosclerosis and in cancer is discussed. We also describe how the balance
      between chaperone requirement and availability becomes disturbed in aged
      organisms, or in other words, how chaperone overload develops. The consequences
      of chaperone overload are also outlined together with several new research
      strategies to assess the functional status of chaperones in the aging process.

PMID- 14580857
TI  - Insulin/IGF-1 signaling pathway driving aging and cancer as a target for
      pharmacological intervention.
AB  - Studies in mammals have led to the suggestion that hyperglycemia and
      hyperinsulinemia are important factors both in aging and in the development of
      cancer. Insulin/insulin-like growth factor 1 (IGF-1) signaling molecules that
      have been linked to longevity include DAF-2 and InR and their homologues in
      mammals, and inactivation of the corresponding genes followed by the increase in
      life span in nematodes, fruit flies and mice. It is possible that the life
      prolonging effect of calorie restriction is due to decreasing IGF-1 levels. A
      search of pharmacological modulators of insulin/IGF-1 signaling pathway mimetic
      effects of life span extending mutations or calorie restriction could be a
      perspective direction in regulation of longevity. Some old and new observations
      suggest that antidiabetic biguanides could be promising candidates for both the
      life span extension and the prevention of cancer.

PMID- 14580858
TI  - A high-throughput screening system for genes extending life-span.
AB  - We developed a high-throughput functional genomic screening system that allows
      identification of genes prolonging life-span in the baker's yeast Saccharomyces
      cerevisiae. The method is based on isolating yeast mother cells with extended
      number of cell divisions as indicated by the increased number of bud scars on
      their surface. Fluorescently labelled Wheat Germ Agglutinin was used for specific
      staining of chitin, a major component of bud scars. Screening of a human HepG2
      cDNA expression library in yeast resulted in the isolation of 12 yeast
      transformants with a potentially prolonged life-span. The transgene in one of the
      lines was identified as ferritin light chain (FTL) and studied in more detail.
      Yeast cells containing FTL showed an enhanced iron and H(2)O(2) resistance, a
      reduced cell death rate and an increased number of cell divisions. Overexpression
      of FTL in the nematode Caenorhabditis elegans resulted in a life-span increase of
      8% confirming our yeast observations in a multicellular organism. Our data
      demonstrate that this method permits a fast screening of libraries for hunting
      genes involved in ageing processes.

PMID- 14580859
TI  - Variability of the SIRT3 gene, human silent information regulator Sir2 homologue,
      and survivorship in the elderly.
AB  - The human sirtuin 3 (SIRT3) gene encodes a putative mitochondrial NAD-dependent
      deacetylase (SIRT3) which belongs to the evolutionary conserved family of sirtuin
      2 proteins. Studies in model organisms have demonstrated that SIR2 genes control
      lifespan, while no data are available regarding a possible role of SIRT3 in human
      longevity. By analysing the genotype-specific survival function relevant to the
      G477T marker of SIRT3, we found that in males the TT genotype increases
      (p=0.0272), while the GT genotype decreases (p=0.0391) survival in the elderly.
      Since SIRT3 lies in a chromosomal region (11p15.5) where four genes potentially
      associated with longevity are located (HRAS1, Insulin-like Growth Factor 2,
      Proinsulin, and Tyrosine Hydroxylase) we tested for linkage-disequilibrium
      between G477T alleles and alleles of the above genes. The disequilibrium was not
      significant in any case, thus suggesting that SIRT3 itself, or a gene strictly
      linked to SIRT3, may have a role in human longevity.

PMID- 14580860
TI  - Longevity-associated mitochondrial DNA 5178 A/C polymorphism modulates effects of
      daily drinking and cigarette consumption on serum triglyceride levels in middle
      aged Japanese men.
AB  - Mitochondrial DNA 5178 adenine/cytosine (mt5178 A/C) polymorphism is one of the
      longevity-associated mitochondrial DNA polymorphisms. The frequency of the
      mt5178A genotype is significantly higher in Japanese centenarians than in the
      general population. We previously reported that serum high-density lipoprotein
      cholesterol levels were significantly higher in men with mt5178A than in those
      with mt5178C. However, this significant difference disappeared after adjusting
      for drinking frequency. To investigate the interaction between mt5178 A/C
      polymorphism and habitual drinking on serum lipid levels, we performed an
      association study in 321 healthy middle-aged Japanese men. Interaction between
      mt5178 A/C polymorphism and daily drinking on serum triglyceride (TG) levels was
      observed (P=0.019). Moreover, interaction between mt5178 A/C polymorphism and
      cigarette consumption on serum TG levels was also observed (P=0.022). Multiple
      regression analysis showed that, in men with mt5178A, daily drinking decreased TG
      levels (P=0.025), and cigarette consumption increased TG levels (P<0.001), while
      in men with mt5178C, the effects of daily drinking and cigarette consumption on
      TG levels were unclear. No interaction was observed on other lipid levels.
      Longevity-associated mitochondrial DNA 5178 A/C polymorphism thus influences the
      effects of daily drinking and cigarette consumption on TG levels in middle-aged
      Japanese men.

PMID- 14580861
TI  - Dehydroepiandrosterone-sulfate as a biomarker of senescence in male non-human
      primates.
AB  - Numerous studies have suggested important and varying roles for
      dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulfate (DHEA-S) in
      primate physiological functions. Despite these numerous claims, specific actions
      and significance of DHEA and DHEA-S are still equivocal. A decline of these
      hormones in adult humans may have functional significance, yet there is no clear
      relationship between functional impairments of aging and the decline in DHEA or
      DHEA-S levels. This current study attempts to address the natural history of
      adrenal hormones by presenting non-human primate evidence of the endocrinology of
      aging; the age-related patterns of adrenal hormone decline in three species of
      the subfamily Cercopithecinae, Macaca mulatta, Macaca nemestrina, and Papio
      cynocephalus are compared. It is concluded that DHEA-S and cortisol represent
      lineage specific markers of senescence among primates and that parallel age
      related patterns of DHEA-S and cortisol likely reflect lineage specific effects,
      or rather, phylogenetic similarities of endocrine senescence. The use of relative
      adrenal hormone levels to approximate species' life expectancies is discussed.

PMID- 14580862
TI  - Transcription profiling of estrogen target genes in young and old mouse uterus.
AB  - The goal of this study was to identify age-related changes in the expression of
      estrogen target genes in mouse uterus. We developed a novel 'estrogen response
      element (ERE) Chip' microarray bearing 297 genes including both known estrogen
      target genes and genes identified by searching the mouse genome database to have
      EREs, AP-1 sites, and Sp1 sites, all targets of estrogen receptor (ER)
      regulation. 400-500 bp PCR products of these 297 genes were printed onto nylon
      membranes creating the 'ERE Chip' microarray. This microarray is unique because
      it is the first estrogen-responsive gene-specific microarray to identify changes
      in uterine gene expression in young versus old mice. Using this ERE microarray we
      identified 10 uterine genes whose expression was up-regulated in old mice, e.g.
      beta-actin, calcium binding protein 45a, Sp1, and COUP-TFII. In contrast, the
      expression of only 4 uterine genes, i.e., complement C3, lactoferrin, Muc-1, and
      17-beta-hydroxysteroid dehydrogenase 8 (H2-Ke6) was down-regulated in old mice.
      These changes may reflect an increase in stromal and a decrease in glandular
      epithelial gene expression, and may be associated with age-related changes in
      these tissue compartments within the uterus, possibly leading to the decline in
      reproductive function in C57Bl/6 mice.

PMID- 14580863
TI  - Hepatic sinusoidal pseudocapillarization with aging in the non-human primate.
AB  - BACKGROUND/AIMS: Age-related changes in the hepatic sinusoid termed
      pseudocapillarization have been reported in the rat and human and have
      implications for disease susceptibility in old age. In this study, we
      investigated whether similar changes occur in the livers of old baboons and thus
      represent a widespread aging change. METHODS: Liver tissue from five young
      baboons (5.4+/-0.5yrs) and five old baboons (21.8+/-0.7yrs) was compared by
      transmission electron microscopy, scanning electron microscopy and
      immunohistochemistry. RESULTS: The thickness of the sinusoidal endothelium was
      increased in old baboons (130+/-8 nm versus 186+/-9 nm, P<0.001) and the
      frequency of endothelial fenestrae decreased, with the porosity declining from
      4.2+/-0.5% to 2.4+/-0.4% (P=0.006). The expression of laminin and von Willebrands
      factor was more extensive in old baboons. Novel perisinusoidal ring-shaped cells,
      probably fat-engorged stellate cells, were prominent in the old baboons.
      CONCLUSIONS: Pseudocapillarization is a significant age-related change in the
      baboon liver. Aging in baboons is associated with a novel aging change in the
      stellate cell not reported in other species. Hepatic pseudocapillarization is a
      widespread aging liver change found in several species including humans and other
      non-human primates.

PMID- 14580864
TI  - Hydrogen peroxide induced down-regulation of CD28 expression of Jurkat cells is
      associated with a change of site alpha-specific nuclear factor binding activity
      and the activation of caspase-3.
AB  - CD28 is the requisite co-stimulatory molecule in the activation of T cells and in
      the generation of immune responses. But expression of CD28 declined and oxidants
      accumulated in the elderly. Although accumulation of reactive oxygen species
      (ROS) during senescence has been reported extensively, the effect of oxidants on
      CD28-expression remains totally unknown. In this study, we tried to address the
      molecular mechanism underlying the decrease in CD28-expression of Jurkat T cells
      cultured in H2O2. Our results indicate that H2O2 could partially block the
      expression of CD28. This correlates well with a change of nuclear protein binding
      activity to the motif of site alpha of the CD28 gene, while the site beta-binding
      activity remained unaltered. On the other hand, since caspase-3 is activated by
      H2O2, inhibitors of caspase-3 should increase the expression of CD28. What is
      more interesting is the fact that the site alpha-binding activity was mostly
      restored after caspase-3 inhibitors had being added. However, caspase-3 is not
      activated by caspase-8. Maybe it is activated by caspase-9, which is triggered by
      cytochrome c. We believe that the procaspase-3 is activated by ROS, and the
      active caspase-3 can induce the change of the site alpha-binding activity,
      causing a decrease in CD28 expression.

PMID- 14580865
TI  - The effect of age and gender on cytokine production by human peripheral blood
      mononuclear cells and markers of bone metabolism.
AB  - BACKGROUND: Aging has been associated with various alterations of immune
      functions, the musculoskeletal system and a decline of sex hormone levels.
      Estradiol has a central role in the regulation of bone turnover and also
      modulates the production of cytokines such as interleukin-1 and -6 and tumor
      necrosis factor-alpha. We therefore studied the effect of age and gender on
      cytokine production by mononuclear cells and markers of bone metabolism. METHODS:
      Peripheral blood mononuclear cells were isolated from young and elderly subjects;
      intracellular detection of cytokine production after stimulation with ionomycine
      and PMA (T cells) or LPS (monocytes) was performed by four color flow cytometry.
      Sex hormone levels and markers of bone metabolism were measured by RIA or ELISA:
      RESULTS: When we compared elderly to young women we found an increased proportion
      of T cells that were positive for interferon-gamma, interleukin-2, -4, -10 and 
      13. Also the percentage of cells producing interleukin-4 or interferon-gamma
      within the CD8(+) population was higher in the group of elderly women. In
      contrast, proportionally fewer monocytes of elderly women were positive for tumor
      necrosis factor-alpha or interleukin-6 than those of young women. In elderly men
      a higher percentage of T cells produced interleukin-2, -4 and -13. In the group
      of aged men we found a higher frequency of cells that produced interleukin-4
      within the CD4(+) or CD8(+) population. Moreover, within monocytes of elderly men
      we found an increased percentage of cells positive for both interleukin-1beta and
      tumor necrosis factor-alpha. The data on markers of bone metabolism indicated an
      increase of bone turnover in old age. CONCLUSION: Our data demonstrate that aging
      is associated with significant alterations of bone metabolism and cytokine
      production by T cells and monocytes. For particular cytokines (interferon-gamma
      and interleukin-10 in T cells, interleukin-6 and tumor necrosis factor-alpha in
      monocytes) these changes are gender specific.

PMID- 14580866
TI  - Anti malondialdehyde-adduct immunological response as a possible marker of
      successful aging.
AB  - Contrasting results have been obtained by various researchers about oxidative
      markers of aging. In this study, a healthy over-90-year-old population was
      examined for various plasma oxidative biomarkers and compared with a healthy
      population of blood donors (age range 23-66). Plasma malondialdehyde (MDA),
      evaluated by means of the thiobarbituric acid test, was significantly higher in
      the over-90-year-old population, confirming the presence of increased
      lipoperoxidation in old age. The antibody titre against MDA-protein adducts,
      considered a marker of lipoperoxidative protein damage in vivo, was evaluated in
      an ELISA test, completely home made and calibrated versus a concentrated pool of
      human plasma; this antibody titre was significantly higher in the over-90-year
      old population. Plasma vitamin E, evaluated in RP-HPLC, was not significantly
      different between the two groups. Plasma protein-bound carbonyls, a marker of
      oxidative protein damage, were measured with the 2,4-dinitrophenylhydrazine
      assay; their level in the over-90-year-old population was lower than in the blood
      donors. The higher antibody titre against MDA-adducts may result in protection
      against accumulation of oxidatively damaged proteins by enhancing their removal,
      and, together with the preserved plasma vitamin E level, it may endow over-90
      year-olds with an especially efficient antioxidant profile. The low level of
      protein carbonyl might reflect the more efficient removal of damaged proteins.

PMID- 14580867
TI  - Aged mice exhibit distinct B cell precursor phenotypes differing in activation,
      proliferation and apoptosis.
AB  - Senescence in murine models is associated with a reduction, albeit heterogeneous,
      in bone marrow pre-B cells. We have categorized aged BALB/c mice into two
      phenotypes based on their patterns of pre-B/pro-B cell loss. Each phenotype is
      characterized by distinct responses to the growth cytokine IL-7 and capacity for
      survival in vitro. A 'moderate' loss of late-stage pre-B cells (25-80%) coincided
      with decline in proliferation to rmIL-7. This was also associated with a decrease
      in the frequency of pro-B cells which increased phosphotyrosine content upon IL-7
      stimulation, an indicator of early activation events. A 'severe' loss of pre-B
      cells (>80%) resulted in a reduced pro-B cell pool which retained normal
      activation and proliferative responses to IL-7. B cell precursors from aged mice
      with severe alterations in B lymphopoiesis displayed increased susceptibility to
      apoptosis in comparison to both aged mice with moderate B cell precursor loss and
      young mice. Conceivably, during senescence, aged mice may initially accumulate B
      cell precursors which are poorly responsive to IL-7. Progressively, these
      refractory B cell precursors may be eliminated via apoptosis; however, the
      remaining limited pool of B cell precursors retains the capacity to respond to IL
      7 stimulation.

PMID- 14580868
TI  - Senescence-associated cell death of human endothelial cells: the role of
      oxidative stress.
AB  - Replicative senescence of human endothelial cells was analyzed, using primary
      endothelial cells from the human umbilical vein endothelial cells (HUVEC) as an
      experimental model system. We had shown before that senescent HUVEC arrest in the
      G1 phase of the cell cycle and that a subpopulation of the senescent cells
      undergoes cell death. We now demonstrate that cell death occurs by apoptosis,
      characterized by activation of caspase 3. Using the redox-sensitive dye
      dihydrorhodamine 123, a significant accumulation of reactive oxygen species is
      detected in senescent but not young endothelial cells. To determine if increased
      oxidative stress may contribute to the senescent phenotype, cells were treated
      with tert-butyl hydroperoxide (tBHP), which is known to increase oxidative stress
      by decreasing the intracellular glutathione levels. We show here that mild tBHP
      stress induces a phenotype of premature senescence in a subpopulation of the
      treated cells, which closely resembles the phenotype of naturally senescent
      HUVEC, including growth arrest, senescence-associated beta-gal activity, and
      apoptotic cell death. These results establish a model of premature senescence for
      human endothelial cells, which will be suitable to analyze mechanisms of age
      associated cell death.

PMID- 14580869
TI  - Age-dependent increase of NF-kappaB translocation and PDGF-B expression in aortic
      endothelial cells of hypercholesterolemic rats.
AB  - The objective of this study was to determine whether there was an age-dependent
      difference in promoting nuclear translocation of NF-kappa B and platelet derived
      growth factor expression in aortic endothelial cells between two groups of Wistar
      rats of 2 and 10 months in age, respectively, accompanied by
      hypercholesterolemia. The serum cholesterol levels became significantly higher in
      the older rats after taking a cholesterol-enriched diet for 16 weeks (129.3+/
      11.9 vs. 194.5+/-22.6 mg/dl, P<0.01). The increase in total cholesterol levels
      were due to an elevation of LDL cholesterol since serum HDL cholesterol
      concentrations were similar in rats on either a high cholesterol- or a standard
      diet. Immunohistologic staining revealed nuclear translocation of NF-kappaB in
      aortic endothelial cells of rats was responsible for a high cholesterol uptake by
      cells. PDGF-B production was also increased in the endothelial cells of these
      animals as identified by situ hybridization and immunohistologic staining.
      Interestingly, the intensity of PDGF-B expression in the 10 months old rats was
      markedly higher than those of 2 months old. Taken together, these findings
      provide evidence that there was an elevation of serum cholesterol levels
      coinciding with an increase of PDGF-B expression in older rats, in which NF
      kappaB might be an important transcription factor in mediating a
      hypercholesterolemia-induced PDGF-B expression.

PMID- 14580870
TI  - Aging-related changes in myocardial purine metabolism and ischemic tolerance.
AB  - Impaired tolerance to ischemia-reperfusion in older hearts may stem in part from
      alterations in purine catabolism, impacting on maintenance of energy state and
      protective signaling via extracellular adenosine. We characterized effects of
      aging on normoxic and post-ischemic purine metabolism in hearts from young (2-4
      month), middle-aged (12 month), old (18 month), and senescent (24-28 month)
      C57/Bl6 mice. Normoxic function was similar in all age groups while normoxic
      purine efflux increased gradually with age. This was the result of enhanced
      efflux of hypoxanthine, xanthine and uric acid, with extracellular accumulation
      of adenosine and inosine remaining unchanged. While total purine washout during
      60 min reperfusion following 20 min global ischemia was unaltered by aging
      (1057+/-109 nmoles/g in young vs. 1221+/-127 nmoles/g in senescent hearts),
      selective changes in purine catabolism were evident. Accumulation of adenosine
      and inosine were reduced by 50 and 80%, respectively, matched by 400 and 300%
      elevations in hypoxanthine and xanthine accumulation, respectively. Uric acid
      remained unchanged. Thus, while adenosine and inosine represented 15+/-2 and 47+/
      3% of total purine efflux in young hearts, these values decreased to only 6+/-1
      and 9+/-2% in senescent hearts. Efflux of IMP also increased 500% with aging
      whereas 5'-AMP was unaltered. These changes were associated with a substantial
      fall in ischemic tolerance, with left ventricular developed pressure recovering
      to 46+/-3% in young hearts vs. only 24+/-6, 16+/-4, and 19+/-4% in middle-age,
      old and senescent hearts, respectively. Our data collectively support a
      pronounced shift in purine catabolism, with reduced accumulation of salvageable
      and cardioprotective adenosine, and enhanced accumulation of poorly salvaged (and
      potentially injurious) hypoxanthine and xanthine. Mechanisms underlying this
      shift have yet to be determined. However, this may play a role in the marked
      decline in myocardial tolerance to ischemia with aging and senescence.

PMID- 14580871
TI  - TGF-beta cytokines increase senescence-associated beta-galactosidase activity in
      human prostate basal cells by supporting differentiation processes, but not
      cellular senescence.
AB  - The family of transforming growth factors betas (TGF-betas) comprises molecules
      involved in growth inhibition, stress-induced premature senescence, epithelial
      mesenchymal transition and differentiation processes. The aim of this study was
      to clarify the effect of long term exposure of human prostate basal cells to TGF
      betas, which are found in high concentrations in prostatic fluid and areas of
      benign prostatic hyperplasia (BPH). Basal cell cultures established from prostate
      explants (n=3) were either grown into cellular senescence, or stimulated with TGF
      beta1, beta2 and beta3. Similar to cellular senescence, TGF-beta stimulation
      resulted in an increase of SA-beta galactosidase (SA-beta-gal) activity,
      flattened and enlarged cell morphology, and down-regulation of the inhibitor of
      differentiation Id-1. TGF-beta-treated prostate epithelial cells neither showed
      terminal growth arrest nor induction of important senescence-relevant genes, such
      as p16(INK4A), IFI-6-16, IGFBP-3 or Dkk-3. Cells stained positive for
      cytokeratins 8/18, but did not express other lumenal markers, such as prostate
      specific antigen and androgen-receptors. TGF-betas increased also the expression
      of the mesenchymal marker vimentin, indicating that basal epithelial cells
      underwent differentiation with lumenal and mesenchymal features. In contrast, in
      vitro-differentiated neuroendocrine-like cells from prostate organoide cultures,
      expressing chromogranin A and cytokeratin 18, strongly stained positive for SA
      beta-gal. Thus, SA-beta-gal activity is not only a marker for senescence, but
      also for differentiation of human prostate epithelial cells. With regard to the
      in vivo situation, in addition to cellular senescence, TGF-beta could contribute
      to the increased number of SA-beta-gal positive epithelial cells in BPH.

PMID- 14580872
TI  - The MALVA (MAntova LongeVA) study: an investigation on people 98 years of age and
      over in a province of Northern Italy.
AB  - The MALVA (MAntova LongeVA) study aims at investigating the socio-demographic,
      clinical and genetic characteristics of all subjects over 98 years of age
      residing in the province of Mantova (Northern Italy). In this paper we present
      the study protocol and the main demographic results. Absolute number, prevalence
      ratio and female/male ratio of the subjects aged 98+ and of the centenarians in
      the Mantova province (370,645 inhabitants at 31st December 1997) were checked at
      the baseline of the study (31st March 1998) as well as in the two years preceding
      and following the study. A total of 117 subjects aged 98+ (including 39
      centenarians) were traced at 31st March 1998; the prevalence ratio was 31.6 per
      100000 (12.1 for centenarians), and the female/male ratio was 6.3 (6.5 for
      centenarians). The distribution of the oldest old according to places of birth
      and residence was non-homogeneous across the provincial territory. Seventy-seven
      subjects (66% of the identified subjects) were enrolled in the study and
      administered a protocol including an interview about socio-economic conditions,
      lifetime habits and pathological and pharmacological case histories, as well as
      medical examination, performance-based tests and blood sample collection. Data on
      the socio-demographic characteristics and the health status of very old people in
      the province of Mantova are discussed and compared to findings from previous
      studies on Italian centenarians.

PMID- 14580873
TI  - Response to influenza vaccination in community and in nursing home residing
      elderly: relation to clinical factors.
AB  - Intramuscular (IM) influenza vaccines are about 50% effective in preventing
      respiratory illness among the elderly. The aim of this study was to identify
      factors associated with immune response to influenza vaccination among nursing
      home and community-residing elderly. 114 nursing home (NHE) and 62 community
      residing elderly (CE) were vaccinated with a commercial IM vaccine. Serum
      antibodies were evaluated by HIA, and the impact of subjects' clinical
      characteristics on seroconversion was determined. Factors that were associated
      with low seroconversion among NHE, included: type II diabetes [for B/Harbin:
      p=0.044, OR 0.12, (CI: 0.015-0.94)], and antibody titer prior to vaccination
      A/(H1N1): p=0.03, OR 2.38, (CI: 1.09-5.22); A/(H3N2): p=0.015, OR 2.68 (CI: 1.22
      5.92), B/Harbin: p=0.057, OR 4.46 (CI: 0.96-20.85)]. Factors that were associated
      with lower seroconversion CE elderly, included older age [A/(H1N1): p=0.008, OR
      0.846, (CI 0.75-0.96), B/Harbin: p=0.016, OR 0.812, (CI:0.69-0.96)], and antibody
      titer prior to vaccination A/(H1N1): p=0.029, OR 4.08, (CI: 1.16-14.37);
      A/(H3N2): p<0.0001, OR 11.495 (CI: 3.18-41.55)]. There was no significant
      difference in seroconversion between nursing home residing elderly and community
      elderly. We conclude that Type-II diabetes and antibody titer>1:40 prior to
      vaccination are associated with reduced response to the influenza vaccination in
      nursing home elderly.

PMID- 14580874
TI  - Influence of increased age on the development of herpes stromal keratitis.
AB  - Herpes stromal keratitis (HSK) is the leading infectious cause of blindness in
      the United States and is a consequence of events following HSV-1 infection of the
      eye. The pathology of the disease is currently thought to be caused by a
      destructive, CD4(+) T helper 1 (Th1) type inflammatory immune response within the
      cornea rather than a cytopathic response elicited by the virus. A large
      percentage of people can become infected with HSV-1 as children whereas some
      studies have concluded that many others do not become infected with HSV-1 until
      much later in life. In this paper we investigate the role of increasing age on
      ocular HSV-1 infection. Following an ocular infection of mice with HSV-1 we
      observed greater pathology in the cornea during both early and late time-points
      in adult mice when compared to young animals. No significant differences in viral
      titers were observed in either the eyes or trigeminal ganglia from infected mice,
      regardless of age, suggesting that increased viral load may not be responsible
      for the ocular pathology in the adult mice. We hypothesize that age-related
      changes in the immune response may predispose adult animals to HSK disease.

PMID- 14580875
TI  - The third European congress on biogerontology: the biogerontological basis of
      preventive medicine and geriatric practice.

PMID- 14580876
TI  - Pennington scientific symposium on mechanisms and retardation of aging.

PMID- 14580877
TI  - Purification of bovine IGFBP-3 and the development of an enzyme immunoassay for
      the protein.
AB  - Insulin-like growth factor binding protein-3 (IGFBP-3), the most prominent IGF
      binding protein in serum, has been demonstrated to modulate the effects of the
      IGFs but also to exert IGF-independent actions. Quantification of IGFBP-3 in
      livestock species, in particular ruminants, is commonly limited to blotting
      methods in spite of the importance of these species. Here we describe the
      development of a specific homologous enzyme-linked immunosorbent assay (ELISA) to
      measure bovine IGFBP-3 in bovine plasma, serum and milk. IGFBP-3 purified from
      bovine serum was used both as standard and also for tracer synthesis. A specific
      antiserum was raised in rabbits using a synthetic peptide based on the sequence
      of bovine IGFBP-3. The measuring range of the assay was between 50 and 1000 ng
      IGFBP-3 per milliliter of plasma or milk. Mean recovery was 97.3% for plasma and
      100.1% for milk. Intra- and interassay coefficients of variation were 6.2% and
      9.3%, respectively. For the biological verification of the assay, IGFBP-3 was
      determined in plasma obtained from 12 dairy cows before and after being injected
      with a depot-formulated growth hormone (GH) preparation. GH, a well-characterized
      stimulator of IGFBP-3, led to a 1.3-fold increase of basal IGFBP-3 concentrations
      during days 3 to 19 after the injection. The availability of an ELISA procedure
      which permits precise and sufficiently sensitive quantification of bovine IGFBP-3
      and which can be used on large sample numbers thereby avoiding the need for
      radioactive labels, should facilitate further research studies.

PMID- 14580878
TI  - A novel method for polypeptide design to prepare specific antibody of the peptide
      and applied to immunoassay.
AB  - Peptide was polymerized by a novel method: compound containing double bond
      between two carbons such as acdryloyl chloride was introduced into peptide during
      peptide synthesis, then it was transformed to a polymer which has a poly
      propionyl core matrix with peptide branches by radical polymerization either
      after being cleaved from resin or before being cleaved from resin according to
      the peptide physical-chemical character. According to this design, the
      macromolecules with average MW about 40 kD for poly-Osteogenic Growth Peptide
      (poly-OGP), 25 KD for poly-penetratin could be produced. Poly-OGP was further
      applied for antibody preparation and immunoassays. Immunizing New Zealand
      rabbits, we obtained the antiserum with titer of 2.5x10(4), examined by enzyme
      linked immunosorbent assay (ELISA), without cross-reaction with bovine serum
      albumin (BSA), while the antiserum produced by using BSA as peptide carrier
      strongly reacted with BSA (with titer of more than 50x10(4) for BSA). Based on
      competitive ELISA, the anti-poly-OGP antibody showed much better immunoreactive
      sensitivity than anti-BSA-OGP antibody by comparing their IC(50) toward OGP. The
      antigen determinant of OGP and the OGP content in the serum of mice, determined
      by anti-poly-OGP antibody, showed that the anti-polypeptide antibody can be used
      as tools for immunoassay. Thus, the polypeptide system is not only a new approach
      for preparing synthetic peptide antibody for immunoassays but also provided the
      prospect for preparing synthetic peptide-based vaccine.

PMID- 14580879
TI  - Optimal kinetics for quantification of antigen-induced cytokines in human
      peripheral blood mononuclear cells by real-time PCR and by ELISA.
AB  - Real-time polymerase chain reaction (PCR) has recently been described as a new
      tool to measure and accurately quantify mRNA levels. In this study, we have
      applied this technique to evaluate cytokine mRNA synthesis induced by antigenic
      stimulation with purified protein derivative (PPD) or heparin-binding
      haemagglutinin (HBHA) in human peripheral blood mononuclear cells (PBMC) from
      Mycobacterium tuberculosis-infected individuals. Whereas PPD and HBHA optimally
      induced IL-2 mRNA after respectively 8 and 16 to 24 h of in vitro stimulation,
      longer in vitro stimulation times were necessary for optimal induction of
      interferon-gamma (IFN-gamma) mRNA, respectively 16 to 24 h for PPD and 24 to 96 h
      for HBHA. IL-13 mRNA was optimally induced by in vitro stimulation after 16-48 h
      for PPD and after 48 to 96 h for HBHA. Comparison of antigen-induced Th1 and Th2
      cytokines appears, therefore, valuable only if both cytokine types are analysed
      at their optimal time point of production, which, for a given cytokine, may
      differ for each antigen tested. Results obtained by real-time PCR for IFN-gamma
      and IL-13 mRNA correlated well with those obtained by measuring the cytokine
      concentrations in cell culture supernatants, provided they were high enough to be
      detected. We conclude that real-time PCR can be successfully applied to the
      quantification of antigen-induced cytokine mRNA and to the evaluation of the
      Th1/Th2 balance, only if the kinetics of cytokine mRNA appearance are taken into
      account and evaluated for each cytokine measured and each antigen analysed.

PMID- 14580880
TI  - A novel approach for on line monitoring of apoptotic cell shrinkage in individual
      live lymphocytes.
AB  - The apoptotic process occurs asynchronically in most cell populations and its
      duration is variable. Therefore, the ability to continuously monitor the death
      process occurring in individual blood cells before, during and following
      apoptosis induction is crucial in the evaluation of the efficiency of pro- or
      anti-apoptotic drugs. We applied a kinetic approach by performing real time
      measurements of individual living cells. This approach is based on an easy and
      unique method for monitoring intracellular staining reaction, which accompanied
      early apoptotic cell shrinkage. The intracellular enzymatic reaction rates were
      determined by taking repeated, sequential measurements of fluorescence intensity
      of the same individual cells. These rates were found to correlate with the
      respective radii of the cells under different conditions, and to decrease
      following apoptosis induction. The ability to remeasure the same cell before and
      after apoptosis induction enabled the detection of specific individual
      lymphocytes, which were more susceptible or resistant to pro-apoptotic stimulus.

PMID- 14580881
TI  - A novel cell-based system for the rapid quantitative evaluation of (anti)
      inflammatory potential of test substances.
AB  - The control of NF-kappaB activation is a proven therapeutic strategy in the
      treatment of multiple inflammatory disorders. Drug discovery and development for
      such a therapy demands a battery of assays to reliably demonstrate both clinical
      effectiveness and biological safety of prospective medications. Unlike
      traditional in vitro biochemical analyses, cell-based assays more closely mimic
      the actual in vivo physiologic environment, addressing simultaneously biological
      activity and toxicity issues. A novel assay system, based solely on the drug
      resistance of a genetically engineered cell line, has been developed to provide
      rapid quantitative evaluation of the (anti)-inflammatory potential of test
      substances. The assay principle is based on the ability of bona fide inflammatory
      agents to activate the transcription factor NF-kappaB in cultured cells. In our
      model, expression of a dual drug resistance marker, driven by an NF-kappaB
      dependent minimal promoter, provides a selective and highly sensitive scheme with
      a quantitative readout to detect biochemical agents with pro-or anti-inflammatory
      properties. The novel cell-based system is inexpensive, simple to perform
      (requiring only basic cell culture skills), accurate, and provides sensitivity
      comparable to that of the electrophoretic mobility shift assay and quantitative
      ELISA. In addition, the dual selection capability of the model provides a
      powerful tool to discover novel molecular components of the NF-kappaB signal
      transduction pathway.

PMID- 14580882
TI  - Sensitive and viable identification of antigen-specific CD8+ T cells by a flow
      cytometric assay for degranulation.
AB  - Flow cytometric detection of antigen-specific CD8+ T cells has previously been
      limited to MHC-class I tetramer staining or intracellular cytokine production,
      neither of which measure the cytolytic potential of these cells. Here we present
      a novel technique to enumerate antigen-specific CD8+ T cells using a marker
      expressed on the cell surface following activation induced degranulation, a
      necessary precursor of cytolysis. This assay measures the exposure of CD107a and
      b, present in the membrane of cytotoxic granules, onto the cell surface as a
      result of degranulation. Acquisition of cell surface CD107a and b is associated
      with loss of intracellular perforin and is inhibited by colchicine, indicating
      that exposure of CD107a and b to the cell surface is dependent on degranulation.
      CD107a and b are expressed on the cell surface of CD8+ T cells following
      activation with cognate peptide, concordant with production of intracellular
      IFNgamma. Finally, CD107-expressing CD8+ T cells are shown to mediate cytolytic
      activity in an antigen-specific manner. Measurement of CD107a and b expression
      can also be combined with MHC-class I tetramer labeling and intracellular
      cytokine staining to provide a more complete assessment of the functionality of
      CD8+T cells expressing cognate T cell receptors (TCR).

PMID- 14580883
TI  - Protein phosphorylation in neutrophils monitored with phosphospecific antibodies.
AB  - Protein phosphorylation in neutrophils was monitored with two phosphospecific
      antibodies (pAbs) [termed pPKC(S1) Ab and pPKC(S2) Ab] that recognize products of
      protein kinase C (PKC) and other Arg/Lys-directed Ser/Thr protein kinases. The
      pPKC(S1) Ab bound preferentially to p-Ser/p-Thr residues with Arg or Lys in the 
      3 and -5 positions or the -2 and -3 positions, whereas the pPKC(S2) Ab bound
      preferentially to p-Ser with Arg or Lys in the -2 and +2 positions and with a
      hydrophobic residue at the +1 position. Phosphorylated pleckstrin, myristoylated
      alanine-rich C-kinase substrate (MARCKS), the 47-kDa subunit of the phagocyte
      oxidase (p47-phox) and numerous unidentified proteins that underwent
      phosphorylation during neutrophil stimulation were readily detected with these
      pAbs. Priming effects of tumor necrosis factor alpha (TNF-alpha) and the
      susceptibility of certain reactions in neutrophils to inhibitors of protein
      kinases could also be easily investigated with these reagents. Compared to the
      commonly used 32P-labeling/autoradiographic method, Western blotting with pAbs
      was found to be a faster, safer, more specific and in many cases more sensitive
      approach for monitoring protein phosphorylation events in neutrophils. These pAbs
      may facilitate the identification of several new phosphorylation reactions
      involved in neutrophil stimulation.

PMID- 14580884
TI  - Human population-based identification of CD4(+) T-cell peptide epitope
      determinants.
AB  - A human cell-based method to identify functional CD4(+) T-cell epitopes in any
      protein has been developed. Proteins are tested as synthetic 15-mer peptides
      offset by three amino acids. Percent responses within a large donor population
      are tabulated for each peptide in the set. Peptide epitope regions are designated
      by difference in response frequency from the overall background response rate for
      the compiled dataset. Epitope peptide responses are reproducible, with a median
      coefficient of variance of 21% when tested on multiple random-donor sets. The
      overall average response rate within the dataset increases with increasing
      putative human population antigenic exposure to a given protein. The background
      rate was high for HPV16 E6, and was low for human-derived cytokine proteins. The
      assay identified recall epitope regions within the donor population for the
      protein staphylokinase. For an industrial protease with minimal presumed
      population exposure, immunodominant epitope peptides were identified that were
      found to bind promiscuously to many HLA class II molecules in vitro. The peptide
      epitope regions identified in presumably unexposed donors represent a subset of
      the total recall epitopes. Finally, as a negative control, the assay found no
      peptide epitope regions in human beta2-microglobulin. This method identifies
      functional CD4(+) T-cell epitopes in any protein without pre-selection for HLA
      class II, suggests whether a donor population is pre-exposed to a protein of
      interest, and does not require sensitized donors for in vitro testing.

PMID- 14580885
TI  - One-step quantitative cortisol dipstick with proportional reading.
AB  - Rapid quantitative immuno-detection of haptens by the lateral flow assay without
      "typical" competitive inhibition results is studied. In the present study, we
      describe an immuno-threshold-based assay for the quantification of cortisol. It
      gives a signal which is directly proportional to the cortisol concentration in
      plasma samples with a performance time of only 5 min. This technique provides a
      practical calibration curve with detection limit of 3.5 ng/ml. The precision of
      the assay is 6% (intra-assay coefficient of variation, CV) and 10% (inter-assay
      CV). Cross-reactivity with related steroids is acceptably low: corticosterone
      (3.38%), cortisone (2.08%), deoxycorticosterone (2.00%), 17alpha
      hydroxyprogesterone (0.39%), and progesterone (0.05%). Furthermore, the test
      strips show the advantages of long storage time and high stability that allow
      mass production and preparation of large batches. A one-step cortisol whole blood
      test derived from this plasma lateral flow assay has then been performed. It is a
      rapid chromatographic immunoassay designed for quantitative determination of
      cortisol in whole blood samples. It requires no sample pretreatment and gives
      result within 15 min. In principle, with this rapid and sensitive immunoassay,
      the immuno-test strips can be employed for detecting all low-molecular-weight
      haptens. It may also be a useful and convenient dipstick format for drug
      detection.

PMID- 14580886
TI  - Characterization and application of a Listeria monocytogenes reactive monoclonal
      antibody C11E9 in a resonant mirror biosensor.
AB  - Typical detection of Listeria monocytogenes involves selective enrichment,
      isolation and biochemical testing. Development of antibodies to Listeria species
      has improved detection; however, most antibodies detect all species of Listeria.
      A previously developed monoclonal antibody (MAb)-C11E9 was examined for its
      reaction to 13 L. innocua and 40 L. monocytogenes strains representing all 13
      serotypes by ELISA. Absorbance values for L. monocytogenes strains were 0.44-3.58
      and for L. innocua 0.22-1.44. ELISA reactions were divided into three arbitrary
      groups of high (Abs 1.0 or higher), intermediate (0.6-0.99) and low (0.18-0.59).
      Most L. monocytogenes strains (32/41, 78%) were in the high group while only 23%
      (3/13) of L. innocua were in the same group. In the Western blot assay, antibody
      reacted with phosphate-buffered saline (PBS) extracted protein preparations of
      52, 66 and 97 kDa. Ribopattern of all strains was analyzed and no clear
      relationship was observed for antibody reaction and ribotype of a given strain.
      MAb C11E9 was used in a resonant mirror biosensor (IAsys sensor), but failed to
      detect any viable intact L. monocytogenes cells at levels as high as 10(8)
      cells/ml; however, it showed binding (85-150 arc/s) with the surface protein
      preparations containing the 97-, 66- and 52-kDa proteins at 208 mug/ml. Binding
      kinetics of L. monocytogenes and L. innocua surface protein extracts showed
      significantly (p<0.05) higher responses than the three other Listeria species (L.
      ivanovii, L. welshimeri and L. grayi), which could be detected in 10-20 min.
      These data corroborate with ELISA results. In summary, this study suggest that
      MAb-C11E9 is suitable for detection of all serotypes of L. monocytogenes despite
      cross-reaction with L. innocua and could be used for detection of soluble protein
      extracts in the resonant mirror (IAsys) biosensor.

PMID- 14580887
TI  - T-cell hybridomas from HLA-transgenic mice as tools for analysis of human antigen
      processing.
AB  - The study of antigen processing and presentation by human antigen presenting
      cells (APC) has been limited by difficulties of producing and maintaining human T
      cell clones. Murine T-cell hybridomas have advantages for detecting specific
      peptide-MHC complexes on APC. Human antigen-specific immortalized T-cell lines
      have not been successfully produced. We report and validate the use of transgenic
      mice with human MHC genes for HLA-A2, DR1 and DR4 to produce murine T-cell
      hybridomas that are restricted to human HLA alleles and respond to human
      macrophages, dendritic cells (DC), and B-cell lines. Hybridomas restricted by
      human MHC-I and -II specific for influenza matrix protein, tetanus toxoid,
      diphtheria antigen CRM(197), and various M. tuberculosis antigens were produced.
      Epitope specificity was determined for several hybridomas. T hybridomas
      recognized peptide-MHC complexes on fixed APC for analysis of kinetics or
      susceptibility to inhibitors of antigen processing. T hybridomas restricted by
      human MHC represent convenient and powerful tools for the study of antigen
      processing by human APC.

PMID- 14580888
TI  - Tandem IMAC-HPLC purification of a cocaine-binding scFv antibody.
AB  - Immobilized metal affinity chromatography (IMAC) has rapidly become one of the
      most widespread affinity purification techniques employed in recombinant protein
      expression. However, the high purity demands of certain applications are
      occasionally unattainable through a single IMAC separation. GNC92H2scFv is a
      cocaine-binding single-chain antibody fragment that is unstable during long-term
      storage in aqueous solution. To circumvent this problem, a reversed-phase HPLC
      separation was performed following IMAC purification of GNC92H2scFv from
      Escherichia coli cell culture supernatant. The resulting HPLC effluent was then
      freeze-dried to afford a salt-free lyophilizate amenable to long-term storage
      with minimal loss in binding activity. HPLC purification also effectively removed
      an 80-kDa protein contaminant that co-eluted with the IMAC-purified protein. Of
      special importance for in vivo applications of recombinantly expressed protein
      therapeutics, an HPLC purification step afforded a 1000-fold reduction in
      lipopolysaccharide (LPS) endotoxin contamination in the final GNC92H2scFv
      product.

PMID- 14580889
TI  - Affibody-beta-galactosidase immunoconjugates produced as soluble fusion proteins
      in the Escherichia coli cytosol.
AB  - Recombinant immunoconjugates constitute a novel class of immunoassay reagents
      produced by genetic fusion between an antigen recognizing moiety and a reporter
      enzyme or fluorescent protein, obviating the need for chemical coupling. In this
      work, we describe the construction, Escherichia coli production and
      characterization of recombinant beta-galactosidase (beta-gal)-based
      immunoconjugates directed to human immunoglobulin A (IgA). As the antigen
      recognizing moieties, either monovalent or dimeric (head-to-tail) versions of an
      IgA-specific affibody (Z(IgA1)) were used, previously selected in vitro from a
      protein library based on combinatorial engineering of a single staphylococcal
      protein A domain. To increase the likelihood of proper presentation on the
      assembled homotetrameric enzyme surface, the affibody moieties were linked to the
      N-terminus of the enzyme subunits via a heptapeptide linker sequence. The two
      resulting immunoconjugates Z(IgA1)-beta-gal and (Z(IgA1))(2)-beta-gal, containing
      four and eight affibody moieties per enzyme, respectively, could be expressed as
      soluble and proteolytically stable proteins intracellularly in E. coli from where
      they were purified to high purity by a single anion exchange chromatography step.
      The yields of immunoconjugates were in the range 200-400 mg/l culture. Biosensor
      binding studies showed that both the Z(IgA1)-beta-gal and (Z(IgA1))(2)-beta-gal
      immunoconjugates were capable of selective IgA-recognition, but with an apparent
      higher binding affinity for the variant containing divalent affibody moieties,
      presumably due to avidity effects. The applicability of this class of recombinant
      immunoconjugates was demonstrated by IgA detection in enzyme-linked immunosorbent
      assay (ELISA) and dot-blot analyses. In addition, using human kidney biopsy
      samples from a nephropathy patient, IgA depositions in glomeruli could be
      detected by immunohistochemistry with low background staining of tissue.

PMID- 14580890
TI  - Selection of hapten-specific single-domain antibodies from a non-immunized llama
      ribosome display library.
AB  - Picloram-specific variable fragments (V(HH)s) of heavy chain antibodies (HCAbs)
      were selected from a nai;ve-llama library using ribosome display technology. A
      cDNA library of V(HH)s was constructed from lymphocytes of a non-immunized llama
      and engineered to allow in vitro transcription and translation. With no stop
      codons present on the transcripts, trimeric complexes of ribosomes, mRNAs and
      nascent peptides were produced for affinity selection, i.e. panning. After three
      cycles of panning, seven different V(HH)s all belonging to the V(HH) subfamily 1
      were isolated. Following another three cycles of selection, only two of the seven
      V(HH)s persisted. A comparison of these two sequences with known sequences in the
      literature suggests that point mutations may have been introduced into the DNA
      pool during PCR amplification steps of library construction, panning and/or
      cloning. Three separate point mutations causing three independent amino acid
      changes (nonsynonomous mutations) accumulated in the same sequence and enriched
      throughout the selection protocol, suggesting that these changes confer binding
      advantages. Surface plasmon resonance (SPR) analysis was used to determine
      binding kinetics of the two clones (3-1D2 and 3-1F6) representing the two
      different sets of isolated complementarity determining region (CDR)3s. Measured
      K(D)s were 3 and 254 muM, respectively. The results indicate that ribosome
      display technology can be used to efficiently isolate hapten-specific antibody
      (Ab) fragments from a nai;ve library and concurrently introduce diversity to the
      selected pool thereby facilitating molecular evolution. Ribosome display
      technology can compensate for the limited diversity of a V(HH) nai;ve library and
      provide an unlimited source of affinity-matured immunoactive reagents in vitro.

PMID- 14580891
TI  - Displaying and epitope mapping of CD147 on VCSM13 phages: influence of
      Escherichia coli strains.
AB  - The external domain of a human leukocyte surface molecule, CD147 was displayed on
      the surface of phage. Two Escherichia coli laboratory strains, XL-1 Blue and TG
      1, were chosen to separately propagate the recombinant phages. By sandwich enzyme
      linked immunosorbent assay (ELISA), CD147 on phage particles were individually
      captured by six CD147 mAbs and subsequently detected by anti-M13 conjugated HRP.
      All mAbs specifically bound the CD147 on phage particles derived from TG-1. On
      the contrary, only four of them could recognize the CD147 on phages produced by
      XL-1 Blue. The results indicate that the environment in the TG-1 periplasm is
      more appropriate than that of XL-1 Blue for promoting the suitable folding of
      CD147. This finding emphasizes the importance of selecting the appropriate E.
      coli host for display of a complex protein. The epitopes of CD147 displayed on
      the phage were further mapped by competitive inhibition ELISA, which is a
      reliable and economical method. Certain clusters of mAb recognition areas were
      identified and will provide valuable information for the discovery of the ligand
      for CD147.

PMID- 14580892
TI  - Reversal of cadmium induced oxidative stress by chelating agent, antioxidant or
      their combination in rat.
AB  - The influence of an antioxidant agent such as N-acetyl cysteine (NAC) or mannitol
      on the cadmium chelating ability of monoisoamyl 2,3-dimercaptosuccinate (MiADMS)
      was investigated in cadmium pre-exposed rats. This ester of 2,3
      dimercaptosuccinic acid (DMSA), an accepted drug for lead poisoning, being
      lipophilic in nature was expected to be an efficient cadmium chelator. The
      treatment of cadmium intoxicated animals with MiADMS reversed cadmium induced
      increase in blood catalase, superoxide dismutase (SOD) and malondialdehyde (MDA),
      liver MDA and brain SOD and MDA levels but not the decrease in blood, liver brain
      reduced glutathione (GSH) and increase in oxidized glutathione (GSSG) levels,
      consistent with the lowering of tissue cadmium burden. The administration of NAC
      or mannitol reversed the cadmium induced alterations in blood and liver GSH,
      GSSG, blood catalase, SOD, MDA, liver SOD, MDA and brain MDA levels without
      lowering blood and tissue cadmium contents. However, treatments with the
      combination of MiADMS and NAC or MiADMS and mannitol reversed these alterations
      as well as reduced blood and tissue cadmium concentrations. The combined
      treatment with MiADMS and mannitol was better than that with MiADMS and NAC, and
      was significantly more effective in normalizing blood, liver GSH, GSSG, brain
      GSSG, and their GSH/GSSG ratios than that by either of them alone. The combined
      treatments also improved liver and brain endogenous zinc levels, which were
      decreased due to cadmium toxicity. The results suggest that the administration of
      an antioxidant during chelation of cadmium may provide beneficial effects by
      reducing oxidative stress without its cadmium removing ability.

PMID- 14580893
TI  - Additional investigation on the potentiation of phenytoin teratogenicity by
      fluconazole.
AB  - Fluconazole (FCZ) is a potent inhibitor of the cytochrome P450 (CYP)-mediated
      metabolism of the anti-epileptic agent phenytoin (PHT), a well-known human and
      animal teratogen. It has been postulated that phenytoin must be bioactivated via
      the CYP system to initiate teratogenesis. In contrast with this view, FCZ
      pretreatment has been previously shown to result in a potentiation of PHT
      teratogenesis. The current study was initiated to determine the impact of FCZ
      pretreatment on PHT exposure levels in maternal and embryonal compartments. HPLC
      analysis revealed that under a co-dosing FCZ-PHT regimen resulting in enhanced
      PHT teratogenesis, statistically significant higher PHT levels are detectable in
      maternal plasma and embryonic tissue in comparison to controls. These results
      further argue against a role for CYP system in teratogenic bioactivation of PHT.

PMID- 14580894
TI  - Ptychodiscus brevis toxin enhances the frequency-dependent depression of the
      monosynaptic reflex in neonatal rat spinal cord in vitro.
AB  - The involvement of frequency-dependent depression (FDD) of synaptic transmission
      for the depressant action of the Ptychodiscus brevis toxin (PbTx) was
      investigated in neonatal rat spinal cord in vitro. The stimulation of a dorsal
      root by train of pulses (five stimuli) at different frequencies evoked potentials
      in the ventral root (monosynaptic reflex, MSR). Amplitude of the fifth response
      as percent of first response at 0.1, 0.2, 0.5, 1.0 and 2.0 Hz were 90, 80, 75, 70
      and 50%, respectively. In Mg2+-free medium, PbTx depressed the MSR and also
      enhanced the FDD in a concentration-dependent manner. Further, the PbTx-induced
      depression can well be correlated with the enhancement of FDD (r=0.98). In the
      presence of Mg2+ (1.3 mM), the FDD was greater than that in the absence of Mg2+.
      But in the presence of Mg2+ PbTx did not alter FDD, even though there was 25%
      depression at 28 microM (significantly lesser than in Mg2+-free medium). The
      results indicate that the Mg2+-sensitive component of PbTx-induced depression of
      MSR is mediated via the neuronal systems involving FDD.

PMID- 14580895
TI  - Riddelliine N-oxide is a phytochemical and mammalian metabolite with genotoxic
      activity that is comparable to the parent pyrrolizidine alkaloid riddelliine.
AB  - Pyrrolizidine alkaloids (PAs) and their N-oxide derivatives are naturally-formed
      genotoxic phytochemicals that are widely distributed throughout the world.
      Although, the quantities of PAs and PA N-oxides in plants are nearly equal, the
      biological and genotoxic activities of PA N-oxides have not been studied
      extensively. PA N-oxides are major metabolites of PAs and are generally regarded
      as detoxification products. However, in this study, we report that rat liver
      microsomes converted riddelliine N-oxide to the genotoxic 6,7-dihydro-7-hydroxy-1
      hydroxymethyl-5H-pyrrolizine (DHP) metabolite. Metabolism of riddelliine N-oxide
      by rat liver microsomes under hypoxic conditions (argon) generated predominantly
      the parent PA, riddelliine. The reduction of riddelliine N-oxide to riddelliine
      was diminished, when the metabolism of riddelliine N-oxide with rat liver
      microsomes was conducted aerobically. Rat liver microsomal incubations of
      riddelliine N-oxide in the presence of calf thymus DNA produced a set of DHP
      derived DNA adducts as detected and quantified by 32P-postlabeling/HPLC. The same
      DHP-derived DNA adducts were also found in liver DNA of F344 rats fed riddelliine
      N-oxide or riddelliine. When rats received doses of 1.0 mg/kg riddelliine N-oxide
      for three consecutive days, the level of DNA adducts was 39.9 +/- 0.6
      adducts/10(7) nucleotides, which was 2.6-fold less than that measured in rats
      treated with riddelliine at the same dose. We have previously shown that these
      DHP-derived DNA adducts are produced by chronic feeding of riddelliine and that
      the adduct levels correlated with liver tumor formation. Results presented in
      this paper indicate that riddelliine N-oxide, through its conversion to
      riddelliine, is also a potential genotoxic hepatocarcinogen.

PMID- 14580896
TI  - Free and total 2,5-hexanedione in biological monitoring of workers exposed to n
      hexane in the shoe industry.
AB  - OBJECTIVES: To analyse the role of total 2,5-hexanedione (2,5-HD) compared with
      free 2,5-HD as a biological indicator of exposure to n-hexane at work. METHODS:
      One-hundred and thirty two workers in contact with this solvent during their
      occupation in the shoe industry in the province of Alicante (Spain) were studied.
      Environmental and biological tests were carried out analysing variations of the
      concentration of the metabolite in urine corresponding to different working
      conditions. Environmental exposure was evaluated in each work place using active
      personal monitors and measured by gas chromatography (GC). Dichloromethane
      extracts of the urine samples collected at the end of the working shifts were
      analysed, before (determining free 2,5-HD, the toxic metabolite) and after acid
      hydrolysis (pH 0.1) (yielding the total 2,5-HD) and also by GC. The concentration
      of conjugated metabolite 4,5-dihydroxy-2-hexanone was calculated from the
      difference between total and free 2,5-HD. RESULTS: Free 2,5-HD represented an
      average of 14.2% of the total 2,5-HD determined in urine, and this percentage
      increased significantly (P<0.01) with higher environmental levels of acetone.
      Other factors, such as absorption through the skin (depending on the use of
      gloves) and the day on which samples were taken also significantly affected the
      relation between the two indicators and their respective relationships with
      environmental concentrations of n-hexane. CONCLUSION: Although analyses of the
      relationship between the levels of atmospheric n-hexane and those of metabolites
      in urine show a greater correlation for total 2,5-HD than for free 2,5-HD, our
      results suggest that free 2,5-HD could be a better indicator in evaluating risk
      of exposure to n-hexane, since the concentration is directly related to the
      neurotoxic effect.

PMID- 14580897
TI  - Effects of glycoprotein isolated from Rhus verniciflua stokes on TPA-induced
      apoptosis and production of cytokines in cultured mouse primary splenocytes.
AB  - Glycoprotein of Rhus verniciflua Stokes (RVS glycoprotein) was isolated and
      identified using SDS-PAGE. To study the anti-apoptotic effects of RVS
      glycoprotein on mouse splenocytes, splenocytes were exposed to 100 nM TPA (61.68
      ng/ml) for 3 h with or without RVS glycoprotein (100 microg/ml). Results from our
      experiment showed that RVS glycoprotein protects from splenocyte apoptosis
      induced by 12-O-tetradecanoylphorbol 13-acetate (TPA). We also studied the
      effects of RVS glycoprotein on the proliferation of T/B cells and the production
      of cytokines. Our results showed that Concanavalin A (Con A)-induced T cell
      proliferation and the production of interleukin-2 (IL-2)/interleukin-4 (IL-4)
      were reduced, and that Lipopolysaccharide (LPS)-induced B cell proliferation and
      the Tumor necrosis factor alpha (TNF-alpha) were reduced significantly by the
      addition of 50 microg/ml RVS glycoprotein (P<0.01), compared to the control.
      These results indicate that RVS glycoprotein has the capacity to modulate
      apoptosis, cytokine production and T/B cell proliferation in splenocytes.

PMID- 14580898
TI  - Expression of Clara cell secretory protein in the lungs of rats exposed to
      silicon carbide whisker in vivo.
AB  - Intratracheal instillation studies have shown that exposure to silicon carbide
      whiskers (SiCW), an asbestos substitute, produces pulmonary fibrotic changes,
      suggesting that SiCW might have fibrogenic potential. It has been theorized that
      Clara cell secretory protein (CCSP) plays a critical role in regulating the acute
      inflammatory response in the lung. The present study was conducted to investigate
      the time course of the expression of CCSP in lungs exposed to SiCW in vivo. Male
      Wistar rats were administered 2 mg or 10 mg of SiCW suspended in saline by a
      single intratracheal instillation and were sacrificed at 3 days, 1 week, 1 month,
      3 months and 6 months of recovery time. The expression of CCSP was observed by
      reverse transcriptase-polymerase chain reaction (RT-PCR), Western blot and
      immunostaining. Exposure to 10 mg of SiCW decreased in levels of CCSP mRNA at 3
      days, 1 week, 1 month and 6 months following intratracheal instillation. The
      protein level of CCSP in SiCW-exposed rats was decreased at 1 day, 3 days and 1
      month after a single instillation of 2 and 10 mg. These findings suggest that
      CCSP are involved not only in the acute injury but also in the chronic injury of
      the lung exposed to SiCW.

PMID- 14580899
TI  - Phylogenetic tree facilitates the understanding of gene expression data on drug
      metabolizing enzymes obtained by microarray analysis.
AB  - The gene expression data of drug metabolizing enzymes (DMEs) in male F344 rat
      livers were examined after treatments with phenobarbital (PB), clofibrate (CPIB),
      3-methylcholanthrene (3-MC) or butylated hydroxyanisole (BHA) using an Affymetrix
      GeneChip system. Nucleotide sequence-based phylogenetic trees combined with a
      heat map, that presents both quantitative and qualitative data, were created.
      Most DME gene probes were successfully classified into the corresponding gene
      families, although a few were not due to the presence of non-coding or promoter
      region sequences in the target gene. There were also some data discrepancies
      among probes of the same gene family, indicating the inappropriate design of
      these probes. With this method, microarray probes with confusing nomenclature and
      quality differences can be identified. In addition, a good correlation between
      the gene expression data and protein data was confirmed, indicating the
      usefulness of this method for the comprehensive monitoring of DME activity in rat
      livers treated with xenobiotics.

PMID- 14580900
TI  - Mechanism of clobazam-induced thyroidal oncogenesis in male rats.
AB  - In order to elucidate the mechanisms by which long-term treatment with clobazam
      (CLB), 1,5-benzodiazepine, induces thyroid follicular cell tumors in male rats,
      male Sprague-Dawley (SD) rats were treated orally with 400 mg/kg of CLB for up to
      4 weeks, and the contribution of feedback through elevated thyroid stimulating
      hormone (TSH) was investigated. Measurements taken after 1, 2, and 4 weeks of
      treatment revealed that thyroxine (T4)-UDP-glucuronosyltransferase (T4-UDPGT)
      activity was higher than that of untreated animals. This change was accompanied
      by increase in liver weights and centrilobular hepatocyte hypertrophy. In
      addition, plasma total triiodothyronine (T3) and T4 levels were lower than in the
      untreated rats when measured after 1 week of treatment. However, a high plasma
      TSH level was sustained throughout the 4-week treatment. Thyroid follicular cell
      hypertrophy began after 1 week of treatment, followed by increased thyroid weight
      after 2 weeks. Clearance of exogenous [125I] T4 from the blood of treated rats,
      determined after 4 weeks of treatment, was significantly faster than that in
      untreated rats, whereas iodine uptake and organification in the thyroid glands
      were not affected. These results suggest that CLB increases hepatic T4-UDPGT
      activity leading to acceleration of T4-clearance, which results in decreased
      plasma thyroidal hormones followed by compensatory increase of TSH biosynthesis
      and secretion. Chronic high levels of TSH would exert a continuous growth
      pressure on the thyroid, under which hypertrophic follicular cells can ultimately
      progress to frank neoplasms.

PMID- 14580903
TI  - Apatite-forming ability and mechanical properties of PTMO-modified CaO-SiO2-TiO2
      hybrids derived from sol-gel processing.
AB  - Hydrolysis and polycondensation of triethoxysilane end-capped Poly
      (tetramethylene oxide) (Si-PTMO), tetraethoxysilane (TEOS),
      tetraisopropyltitanate (TiPT) and calcium nitrate (Ca(NO(3))(2)) gave transparent
      monolithics of PTMO-modified CaO-SiO(2)-TiO(2) hybrids. The samples with
      (TiPT)/(TEOS+TiPT) molar ratios from 0 to 0.20 under constant ratio of (Si
      PTMO)/(TEOS+TiPT) of 2/3 in weight were prepared. It was found that the
      incorporation of TiO(2) component into a PTMO-CaO-SiO(2) hybrid results in an
      increase in the apatite-forming ability in a simulated body fluid: the hybrids
      with (TiPT)/(TEOS+TiPT) of 0.10 and 0.20 in mol formed an apatite on their
      surfaces within only 0.5 day. It seemed that, within the range of compositions
      studied, the TiO(2) content little affects the overall mechanical properties:
      Young's modulus were 52-55MPa, tensile strength, 7-9MPa, and strain at failure,
      about 30%. Thus, the organic-inorganic hybrids exhibiting both fairly high
      apatite-forming ability and high capability for deformation were obtained. These
      hybrid materials may be useful as new kind of bioactive bone-repairing materials.

PMID- 14580901
TI  - Toxic interaction between hydroxyurea and 1-beta-D-arabino-furanosylcytosine on
      the DNA of a human hepatoma cell line (HEPG2).
AB  - Hydroxyurea (HU) and 1-beta-D-arabino-furanosylcytosine (AraC) are two compounds
      used to inhibit DNA repair in the comet assay and thereby increase its
      sensitivity. We used RNA synthesis and comet assays to assess the cytotoxic and
      genotoxic effects of HU and AraC in the HepG2 cells after 1, 5, or 21 h of
      exposure to concentrations used to inhibit DNA repair. HU was genotoxic between 2
      and 10 mM after 1 h of exposure and cytotoxic after 21 h. The presence of AraC
      (10, 50, or 100 microM) increased the DNA damage caused by HU (10 mM) suggesting
      a potentiation of the genotoxic effect. The interaction between the two
      inhibitors started after 5 h but was not dependent on the concentrations of AraC.
      Consequently, careful attention is required when employing a combination of HU
      and AraC, as their mechanisms of action could interfere with the interpretation
      of the data from genotoxicity assays.

PMID- 14580904
TI  - Fractography evolution in accelerated aging of UHMWPE after gamma irradiation in
      air.
AB  - We studied the fracture surface evolution of ultra high molecular weight
      polyethylene (UHMWPE) specimens, manufactured from GUR 1050 compression moulded
      sheets, after gamma sterilisation in air followed by different aging times after
      thermal treatment at 120 degrees C. Degradation profiles were obtained by FTIR
      and DSC measurements after 0, 7, 14, 24 and 36h aging. We observed by SEM the
      morphology patterns at these aging times, in surface fractographies after
      uniaxial tensile test of standardised samples. The results pointed out clear
      differences between short and long aging times. At shorter times, 7h, the
      behaviour was similar to non-degraded UHMWPE, exhibiting ductile behaviour. At
      longer times, 24-36h, this thermal protocol provided a highly degraded zone in
      the subsurface, similar to the white band found after gamma irradiation in air
      followed by natural aging, although closer to the surface, at 150-200mum. The
      microstructure of this oxidation zone, similarly found in gamma irradiated
      samples shelf-aged for 6-7 years, although with different distribution of
      microvoids, was formed by fibrils, associated with embrittlement of the oxidised
      UHMWPE. In addition, the evolution of the oxidation index, the enthalpy content,
      the mechanical parameters, and the depth of the oxidation front deduced from the
      fractographies versus aging time showed that a changing behaviour in the
      degradation rate appeared at intermediate aging times.

PMID- 14580905
TI  - Attachment and proliferation of neonatal rat calvarial osteoblasts on Ti6Al4V:
      effect of surface chemistries of the alloy.
AB  - This study examined the cell attachment and proliferation of neonatal rat
      calvarial osteoblasts on Ti6Al4V alloy as affected by the surface modifications.
      The modifications could alter simultaneously the surface chemistries of the alloy
      (elemental difference of Ti, Al, V, Cu and Ni about 300-600mum thick examined by
      EDS) as well as the XPS nano-surface characteristics of oxides on the metal
      surface (chemistries of oxides, amphoteric OH group adsorbed on oxides, and oxide
      thickness). Three materials including two from modifications and a control were
      examined. It is argued that a slight change of the nano-surface characteristics
      of oxides as a result of the modifications neither alters the in vitro capability
      of Ca and P ion adsorption nor affects the metal ion dissolution behavior of the
      alloy. This implies that any influence on the cytocompatibility of the materials
      should only be correlated to the effect of surface chemistries of the alloy and
      the associated metal ion dissolution behavior of the alloy. The experimental
      results suggest that the cell response of neonatal rat calvarial osteoblasts on
      the Ti6Al4V alloy should neither be affected by the variation of surface
      chemistries of the alloy in a range studied.

PMID- 14580906
TI  - Biostability and biocompatibility of a surface-grafted phospholipid monolayer on
      a solid substrate.
AB  - We have previously demonstrated phosphorylcholine monolayer chemically grafted
      onto a methacryloyl-terminated solid substrate by in situ polymerization. The in
      situ polymerization was carried out at the interface between a pre-assembled
      acrylated phospholipid monolayer produced by vesicle fusion and a methacryloyl
      terminated substrate using a water-soluble initiator, 2,2'-azobis(2
      methylpropionamidine) dihydrochloride (AAPD). Herein, we examined the
      biostability and biocompatibility of a surface-grafted phospholipid monolayer
      (poly-PC) on a methacryloyl-terminated substrate using a "wash off' test, in
      vitro protein adsorption and in vivo cage implantation for time intervals of 4,
      7, 14 and 21 days, respectively. In order to compare the biostability and
      biocompatibility of phospholipid surfaces on solid substrates, we used two types
      of phospholipid surfaces: a physically adsorbed phospholipid monolayer (PC) and a
      poly-PC. Atomic force microscopy and water contact angle measurements indicated
      that the poly-PC surface was more stable in PBS, Triton X-100 and to EO gas
      sterilization than the PC surface. The adsorption of proteins such as albumin,
      fibrinogen, IgG and human plasma proteins on the poly-PC surfaces were
      significantly reduced, in vitro. Moreover, the poly-PC surface greatly reduced
      macrophage adhesion and the formation of foreign body giant cells, in vivo.

PMID- 14580907
TI  - Endpoint-attached heparin blocks neutrophil sticking and spreading.
AB  - Neutrophils adhere to polymer surfaces by partly unknown mechanisms. Heparin
      coating of such surfaces is employed to improve biocompatibility of
      extracorporeal circulation. The aim of the study was to investigate mechanisms
      for interactions between neutrophils and uncoated versus heparin-coated surfaces.
      Isolated human neutrophils were incubated in tissue culture plates. Uncoated
      plates induced sticking and spreading of unstimulated neutrophils. Heparin
      coating reduced sticking by approximately 75%, and adherent cells were less
      spread (p<0.001). Experiments in plates coated with modified heparins showed that
      sticking and spreading were not related to anticoagulatory ability or surface
      charge. Unstimulated neutrophil sticking was unchanged whether the media
      contained divalent cations or 1mM ethylenediaminetetraacetic acid (EDTA).
      Spreading on uncoated plates was greater in the presence of Ca(2+) and/or Mg(2+)
      than with EDTA. Spreading of unstimulated neutrophils on heparin-coated plates
      varied little with different media. Pre-incubation with anti-CD11b/CD18
      antibodies did not significantly influence adhesion to heparin-coated plates.
      There were no differences in expression of the antiadhesive receptor CD43
      (leukosialin) on adherent neutrophils on uncoated and heparin-coated plates, and
      pre-incubation with anti-CD43 antibody had little effect on neutrophil sticking.
      These data indicate an adhesive mechanism independent of selectins, integrins,
      and leukosialin, and inhibition of sticking and spreading by heparin-coating.

PMID- 14580908
TI  - Endothelial and vascular smooth muscle cell function on poly(lactic-co-glycolic
      acid) with nano-structured surface features.
AB  - Biomaterials that successfully integrate into surrounding tissue should match not
      only the tissue's mechanical properties, but also its topography. The cellular
      response to a biomaterial may be enhanced in synthetic polymer formulations by
      mimicking the surface roughness created by the associated nano-structured extra
      cellular matrix components of natural tissue. As a first step towards this
      endeavor, the goal of the present in vitro study was to use these design
      parameters to develop a synthetic, nano-structured, polymeric biomaterial that
      promotes cell adhesion and growth for vascular applications. In a novel manner,
      poly(lactic-co-glycolic acid) (PLGA) (50/50wt% mix) was synthesized to possess a
      range (from micron to nanometer) of surface features. Reduction of surface
      features was accomplished by treating conventional PLGA with various
      concentrations of NaOH for select periods of time. Results from cell experiments
      indicated that, compared to conventional PLGA, NaOH treated PLGA enhanced
      vascular smooth muscle cell adhesion and proliferation. However, PLGA prepared by
      soaking in NaOH decreased endothelial cell adhesion and proliferation compared to
      conventional PLGA. After further investigation, this finding was determined to be
      a result of chemical (and not topographical) changes during polymer synthesis.
      Surface chemistry effects were removed while retaining nano-structured topography
      by using polymer/elastomer casting methods. Results demonstrated that endothelial
      and smooth muscle cell densities increased on nano-structured cast PLGA. For
      these reasons, the present in vitro study provided the first evidence that nano
      structured surface features can significantly improve vascular cell densities;
      such design criteria can be used in the synthesis of the next-generation of more
      successful tissue-engineered vascular grafts.

PMID- 14580909
TI  - Glutaraldehyde cross-linked hydroxyapatite/collagen self-organized
      nanocomposites.
AB  - To control the mechanical properties and biodegradability of self-organized
      hydroxyapatite/collagen (HAp/Col) nanocomposites, cross-linkage was introduced
      into the composites with glutaraldehyde (GA). The HAp/Col composite suspensions,
      prepared by a simultaneous titration method and aged for 3h, were cross-linked
      with the reagents for 10min under vigorous stirring. The precipitates obtained
      were filtrated and compacted by dehydration under a uniaxial pressure. The
      particle size distribution, 3-point bending strength, contained water amount and
      swelling ratio of the composites were examined as a function of cross-linkage
      amount; the biodegradability was estimated by animal tests using rabbits. As
      regards the cross-linked composites, no long-rage alignment of HAp crystals along
      collagen molecules was found with a transmission electron microscope, suggesting
      that the cross-linking reagents suppressed their long-range self-organization
      mechanism. The 3-point bending strength increased with the GA content and took a
      maximal value at 1.35mmol/g(col). The animal tests indicated no toxicity and
      osteoclastic resorption with good osteoconductivity. The resorption rate was
      decreased with increasing GA concentration. These results suggest that GA cross
      linkage controls mechanical properties and resorption rate without reducing high
      biocompatibility of the composite.

PMID- 14580910
TI  - Effect of water-soluble phospholipid polymers conjugated with papain on the
      enzymatic stability.
AB  - To maintain enzymatic activity during long-term storage by conjugation with water
      soluble 2-methacryloyloxyethyl phosphorylcholine (MPC) polymers (PMPC-COOH)
      having various molecular weights with a carboxylic group on the terminal, such
      compounds were synthesized as a polymer modifier using a photoinduced living
      radical polymerization technique. A poly(ethylene oxide) with a carboxyl group
      (PEO-COOH) was used as the control. The PMPC-COOHs were reacted with the amino
      groups of the enzyme, papain, via amide bonds. With an increase in the molecular
      weight in the range between 5 and 20K of the PMPC-COOH, the modification degree
      and alpha-helix content of the conjugated papain slightly decreased, but the
      remaining enzymatic activity did not depend on the molecular weight of the PMPC
      COOH. However, when a much higher molecular weight PMPC-COOH (40K) was conjugated
      with a reduction in the modification degree, alpha-helix content was higher
      compared with the other PMPC-conjugated papain. Modification with PEO-COOH showed
      little reduction of the alpha-helix content of papain. The time dependence of the
      remaining enzymatic activity of the polymer-conjugated papains was evaluated
      during storage at 40 degrees C. The native papain diminished activity within one
      week. PEO-conjugated papain had decreased activity with time, but after one week
      it had half its initial level. The same tendency was observed when papain was
      modified with PMPC-COOHs 5 and 40K, that is, the enzymatic activity did not
      decrease even when they were stored for 4 weeks. We concluded that the PMPC chain
      could stabilize the enzyme by control of the molecular weight of the PMPC and
      modification degree to the enzyme.

PMID- 14580911
TI  - Rapid fibroblast adhesion to 27nm high polymer demixed nano-topography.
AB  - It is well known that many cell types react strongly to micro-topography. It is
      rapidly becoming clear than cells will also react to nano-topography. Polymer
      demixing is a rapid and low-cost chemical method of producing nano-topography.
      This manuscript investigates human fibroblast response to 27nm high nano-islands
      produced by polymer demixing. Cell spreading, cytoskeleton, focal adhesion and
      Rac localisation were studied. The results showed that an initial rapid adhesion
      and cytoskeletal formation on the islands at 4 days of culture gave way to poorly
      formed contacts and vimentin cytoskeleton at 30 days of culture.

PMID- 14580912
TI  - Biodegradable poly(ether ester urethane)urea elastomers based on poly(ether
      ester) triblock copolymers and putrescine: synthesis, characterization and
      cytocompatibility.
AB  - Polymers with elastomeric mechanical properties, tunable biodegradation
      properties and cytocompatibility would be desirable for numerous biomedical
      applications. Toward this end a series of biodegradable poly(ether ester
      urethane)urea elastomers (PEEUUs) based on poly(ether ester) triblock copolymers
      were synthesized and characterized. Poly(ether ester) triblock copolymers were
      synthesized by ring-opening polymerization of epsilon-caprolactone with
      polyethylene glycol (PEG). PEEUUs were synthesized from these triblock copolymers
      and butyl diisocyanate, with putrescine as a chain extender. PEEUUs exhibited low
      glass transition temperatures and possessed tensile strengths ranging from 8 to
      20MPa and breaking strains from 325% to 560%. Increasing PEG length or decreasing
      poly(caprolactone) length in the triblock segment increased PEEUU water
      absorption and biodegradation rate. Human umbilical vein endothelial cells
      cultured in a medium supplemented with PEEUU biodegradation solution suggested a
      lack of degradation product cytotoxicity. Endothelial cell adhesion to PEEUUs was
      less than 60% of tissue culture polystyrene and was inversely related to PEEUU
      hydrophilicity. Surface modification of PEEUUs with ammonia gas radio-frequency
      glow discharge and subsequent immobilization of the cell adhesion peptide Arg-Gly
      Asp-Ser increased endothelial adhesion to a level equivalent to tissue culture
      polystyrene. These biodegradable PEEUUs thus possessed properties that would be
      amenable to applications where high strength and flexibility would be desirable
      and exhibited the potential for tuning with appropriate triblock segment
      selection and surface modification.

PMID- 14580913
TI  - The effect of surface chemistry and nanotopography of titanium nitride (TiN)
      films on primary hippocampal neurones.
AB  - The cell-substrate interaction of primary hippocampal neurones with thin films of
      TiN was studied in vitro. TiN films of different surface chemistries and
      topographies were deposited by pulsed DC reactive magnetron sputtering and closed
      field unbalanced magnetron sputter ion plating by Teer Coatings Ltd., Hartlebury,
      UK to result in TiN films with similar surface chemistries but different
      topographical features. TiN films were characterised using X-ray diffraction, X
      ray photoelectron spectroscopy and atomic force microscopy. The neuron-substrate
      interaction was examined using environmental scanning electron microscopy (FEG
      ESEM) for morphological information. Bromodeoxyuridine and TUNEL assays were used
      to identify proliferating neurones as well as apoptotic neurones. Fluorescent
      staining for MAP-2 was used to label neuronal network formation. Primary
      hippocampal neurones were found to attach and spread to all of the TiN film
      chemistries and topographies investigated. Neuronal network morphology appeared
      to be more preferential on the nitrogen rich TiN films and also with reduced
      nanotopographical features.

PMID- 14580914
TI  - Construction of multilayer coating onto poly-(DL-lactide) to promote
      cytocompatibility.
AB  - Thin polymer films were formed on poly-(DL-lactide) (PDL-LA) using
      polyelectrolyte multilayer technique to promote the chondrocyte
      cytocompatibility. PDL-LA substrates were activated by poly-(ethylenimine) to
      obtain stable positively charged surface. The polyelectrolytes such as alginate
      and poly-(L-lysine) were alternatively deposited onto the activated PDL-LA
      substrates. The multilayer-modified PDL-LA films were investigated by X-ray
      photoelectron spectroscopy, attenuated total reflection FTIR, contact angle and
      atomic force microscopy. The in vitro chondrocyte test indicated that the
      multilayer-modified PDL-LA substrates promoted chondrocyte attachment and growth.
      In comparison to conventional coating methods, polyelectrolyte multilayers are
      easy to prepare and the procedure is valid whatever the shape of the solid. It
      allows broad medical applications for drug delivery and tissue engineering.

PMID- 14580915
TI  - Characterization and protein-adsorption behavior of deposited organic thin film
      onto titanium by plasma polymerization with hexamethyldisiloxane.
AB  - Plasma polymerized hexamethyldisiloxane (HMDSO) thin film was deposited onto
      titanium using a radio-frequency apparatus for the surface modification of
      titanium. A titanium disk was first polished using colloidal silica at pH=9.8.
      Plasma-polymerized HMDSO films were firmly attached to the titanium by heating
      the titanium to a temperature of approximately 250 degrees C. The thickness of
      the deposited film was 0.07-0.35mum after 10-60min of plasma polymerization. The
      contact angle with respect to double distilled water significantly increased
      after HMDSO coating. X-ray photoelectron spectroscopy revealed that the deposited
      thin film consisted of Si, C, and O atoms. No Ti peaks were observed on the
      deposited surface. The deposited HMDSO film was stable during 2-weeks immersion
      in phosphate buffer saline solution. Fourier transform reflection-absorption
      spectroscopy showed the formation of Si-H, Si-C, C-H, and Cz.dbnd6;O bonds in
      addition to Si-O-Si bonds. Quartz crystal microbalance-dissipation measurement
      demonstrated that the deposition of HMDSO thin films on titanium has a benefit
      for fibronectin adsorption at the early stage. In conclusion, plasma
      polymerization is a promising technique for the surface modification of titanium.
      HMDSO-coated titanium has potential application as a dental implant material.

PMID- 14580916
TI  - Preparation of porous scaffolds by using freeze-extraction and freeze-gelation
      methods.
AB  - Freeze-fixation and freeze-gelation methods are presented in this paper which can
      be used to prepare highly porous scaffolds without using the time and energy
      consuming freeze-drying process. The porous structure was generated during the
      freeze of a polymer solution, following which either the solvent was extracted by
      a non-solvent or the polymer was gelled under the freezing condition; thus, the
      porous structure would not be destructed during the subsequent drying stage.
      Compared with the freeze-drying method, the presented methods are time and energy
      saving, with less residual solvent, and easier to be scaled up. Besides, the
      problem of formation of surface skin can be resolved and the limitation of using
      solvent with low boiling point can be lifted by the presented methods. With the
      freeze-extraction and freeze-gelation methods, porous PLLA, PLGA, chitosan and
      alginate scaffolds were successfully fabricated. In addition to the presentation
      of the morphologies of the fabricated scaffolds, preliminary data of cell culture
      on them are as well included in the present work.

PMID- 14580917
TI  - Studies on biodegradation and release of gentamicin sulphate from
      interpenetrating network hydrogels based on poly(acrylic acid) and gelatin: in
      vitro and in vivo.
AB  - Interpenetrating network hydrogels (IPNs) based on poly(acrylic acid) and gelatin
      (Ge) were evaluated for in vitro and in vivo biodegradation and in vivo release
      of gentamicin sulphate. In vitro and in vivo degradation studies demonstrated
      that with the increase of acrylic acid content in the polymer, the rate of
      degradation decreases, and a reverse phenomenon was observed with increasing Ge
      content in the hydrogel. The rate of in vivo degradation was much lower than in
      vitro degradation. Incorporation of gentamicin sulphate in hydrogel further
      reduces their degradation. In vitro and in vivo drug release profile showed a
      burst effect, followed by controlled release. Drug concentration was measured in
      the local skin tissue, blood serum, kidney, liver and spleen. The local skin
      tissue concentration of 50% and 100% gentamicin sulphate, loaded full IPNs (i.e.,
      Ax-1 and Ax-2), was found to be higher (20+/-2mug/g) than the minimum
      bactericidal concentration for Staphylococcus aureus (1.2mug/g) and Pseudomonas
      aeruginosa (10mug/g), respectively, for a study time of 60 days.

PMID- 14580918
TI  - Hyaluronan microspheres for sustained gene delivery and site-specific targeting.
AB  - Hyaluronan is a naturally occurring polymer that has enjoyed wide successes in
      biomedical and cosmetic applications as coatings, matrices, and hydrogels. For
      controlled delivery applications, formulating native hyaluronan into microspheres
      could be advantageous but has been difficult to process unless organic solvents
      are used or hyaluronan has been modified by etherification. Therefore, we present
      a novel method of preparing hyaluronan microspheres using adipic dihydrazide
      mediated crosslinking chemistry. To evaluate their potential for medical
      applications, hyaluronan microspheres are incorporated with DNA for gene delivery
      or conjugated with an antigen for cell-specific targeting. The results show that
      our method, originally developed for preparing hyaluronan hydrogels, generates
      robust microspheres with a size distribution of 5-20mum. The release of the
      encapsulated plasmid DNA can be sustained for months and is capable of
      transfection in vitro and in vivo. Hyaluronan microspheres, conjugated with
      monoclonal antibodies to E- and P-selectin, demonstrate selective binding to
      cells expressing these receptors. In conclusion, we have developed a novel
      microsphere preparation using native hyaluronan that delivers DNA at a controlled
      rate and adaptable for site-specific targeting.

PMID- 14580920
TI  - Micro-X-ray diffraction observation of nickel-titanium orthodontic wires in
      simulated oral environment.
AB  - A micro-X-ray diffraction (micro-XRD) technique has been employed to determine
      the phases in two superelastic nickel-titanium orthodontic wires that exhibit
      shape memory in the oral environment and one superelastic nickel-titanium wire
      that does not exhibit shape memory in vivo. The micro-XRD analyses were performed
      over the clinically relevant temperature range of 0-55 degrees C, which
      corresponds to the ingestion of cold and hot liquids, and both straight and bent
      (135 degrees ) test samples were analyzed. The results showed that for straight
      (as-received) test samples, the rhombohedral phase (R-phase) was definitely
      present in one shape memory wire product and perhaps in the other shape memory
      wire product, but was apparently absent in the superelastic wire product that did
      not display shape memory. Martensite was observed in all three wire products
      after bending. Phase transformations occurred with temperature changes simulating
      the oral environment for straight test samples of the two shape memory wires, but
      the micro-XRD pattern changed minimally with temperature for straight test
      samples of the superelastic wire and for bent test samples of all three wire
      products. The phase transformations revealed by micro-XRD were consistent with
      results recently found by temperature-modulated differential scanning
      calorimetry.

PMID- 14580919
TI  - Preparation and characterization of starch/cyclodextrin bioadhesive microspheres
      as platform for nasal administration of Gabexate Mesylate (Foy) in allergic
      rhinitis treatment.
AB  - Bioadhesive and biodegradable microspheres were obtained by chemical cross
      linking with epichlorohydrin of an alkaline solution of a mixture of starch and
      alpha-, beta-, or gamma-cyclodextrin (CyD). Microspheres were characterized by
      scanning electron microscopy, swelling degree, and water retention. The
      percentage of the effective CyD in microspheres was estimated by measuring the
      amount of iodine and typical organic compounds (TOCs) retained in the hydrophobic
      cavity of CyD. Gabexate Mesylate (trade name Foy); GM), an antiallergic drug, was
      included in microspheres by soaking in an aqueous solution containing the drug,
      followed by solvent evaporation or lyophilization. UV, IR, and DSC data indicated
      that despite the fact that GM is a hydrophilic drug, its hydrophobic moiety close
      to the benzene ring is able to penetrate the CyD cavity and to form stable
      inclusion complexes. Values of the association equilibrium constant for GM
      binding to CyD, obtained by UV differential spectroscopy, indicated that the
      affinity of the drug for alpha- and gamma-CyD is higher than that for beta-CyD.
      In vitro, GM was gradually released during 1h. Even if the release rate of the
      drug is relatively fast, the microspheres might actually provide the best
      platform since the material adheres to the nasal mucosa which was proved by
      adhesion tests. The GM integrity was checked by comparing its anti-trypsin
      activity before and after release.

PMID- 14580921
TI  - Pore size, tissue ingrowth, and endothelialization of small-diameter microporous
      polyurethane vascular prostheses.
AB  - Small-diameter microporous polyurethane vascular prostheses with an average pore
      size of between 5 and 30mum at the outer surfaces and 30mum at the luminal
      surface were prepared. Thirty-two PU and 8 expanded polytetrafluoroethylene
      (ePTFE) prostheses were implanted into the abdominal aorta of rats for periods
      ranging from 1 to 8 weeks. Harvested prostheses were analysed histologically and
      morphologically. The progress of endothelial-like cells and the extent of
      infiltration of perigraft tissues were quantified. All of the prostheses showed
      fast growth of endothelial-like cells in the second week, with the PU prostheses
      having an external pore size of 30mum producing the highest rate. It was also
      during the second week that perigraft tissue grew most significantly into the
      prosthetic structure. This coincident may suggest the importance of rapid tissue
      regeneration for the early endothelial healing. The role of the ingrowth
      perigraft tissues is likely to support and stabilize the neointima. The
      thickening of neointima was mainly located at the vicinity of the proximal
      anastomoses of some of the PU prostheses and was unrelated with the extent of
      perigraft tissue infiltration. In the PU prostheses, a complete lining of
      endothelial-like cells was achieved by the end of 4 weeks. Expanded PTFE
      prostheses displayed smooth, thin intima, very limited tissue ingrowth, and
      incomplete coverage of endothelial-like cells.

PMID- 14580922
TI  - Soft steroids: a new approach to the treatment of inflammatory airways diseases.
AB  - Inhaled synthetic glucocorticosteroids are widely used in the treatment of
      bronchial asthma where they provide very effective first line treatment. However,
      a range of unwanted side effects and the often complex dosing schedules
      associated with these drugs frequently result in poor patient compliance. The
      soft drug approach has been utilised as a means of delivering these potent anti
      inflammatory agents close to their site of action while reducing the degree of
      systemic exposure and thus limiting or eliminating the associated systemic and
      local side effects. A further target for pharmaceutical companies is to deliver
      these new treatments in a once daily formulation thus further enhancing patient
      compliance. While many soft steroids have failed to progress into the clinic two
      are meeting with some degree of success. Loteprednol etabonate, an inactive
      metabolite soft steroid, has been accepted for the treatment of ophthalmic
      disorders and is being examined in clinical trials for its effects on airway
      inflammation. Ciclesonide, a pro-drug soft steroid, has demonstrated efficacy
      without side effects in a once daily formulation in asthma patients and is being
      developed for the treatment of both asthma and chronic obstructive pulmonary
      disease with launches of a once daily inhaler formulation expected in 2003. These
      drugs may represent a significant step forward in the treatment of inflammatory
      diseases of the airways.

PMID- 14580923
TI  - The use of surfactant in children with acute respiratory distress syndrome:
      efficacy in terms of oxygenation, ventilation and mortality.
AB  - PURPOSE: The aim of this prospectively designed study was to investigate the
      efficacy of surfactant (S) for acute respiratory distress syndrome (ARDS) in
      children. MATERIALS AND METHODS: Children with ARDS were included in this study.
      Surfactant (Survanta, Abbott, USA) was given intratracheally at a dose of 150
      mg/kg every 12 h for a total of two doses. During the study period none of the
      patients received permissive hypercapnia, high frequency ventilation, nitric
      oxide or ECMO. Peak inspiratory pressure (PIP), positive end expiratory pressure
      (PEEP), ventilation rate, mean airway pressure, tidal volume (TV), Murray index,
      PaO2/FiO2, ventilation index (VI), oxygen index (OI) and arterial oxygen tension
      difference (A-aDO2) were measured before and 48 h after surfactant treatment.
      Duration of mechanical ventilation therapy, duration in paediatric intensive care
      unit (PICU) and mortality rate were recorded. RESULTS: Among the 36 children who
      met the inclusion criteria, 12 were treated with surfactant. The mean age was
      72.5+/-56.2 months; 47% of children were male. Infants were ventilated by
      pressure-controlled ventilators whereas for older children volume-controlled
      ventilators were used. Sepsis (42%) was the main predisposing factor followed by
      pneumonia (25%) and malignancy (17%). The baseline characteristics including age,
      predisposing factors, gender, PIP, PEEP, A-aDO2, PaO2/FiO2, OI, TV, VI and Murray
      index were similar in the surfactant and non-surfactant (NS) group (p>0.05).
      There were significant improvements in PIP, PEEP, A-aDO2, PaO2/FiO2, OI, TV, VI
      and Murray index in the surfactant group after surfactant treatment compared with
      NS group (p<0.05). Duration of PICU stay and ventilator treatment was longer in
      NS group (14+/-3.7, 1.8+/-3.2 days vs. 9.2+/-3.1, 8.6+/-1.9 days), (p<0.05).
      Mortality rate was 42% in surfactant compared with 63% in the NS group, (p>0.05).
      Children in the surfactant group lived significantly longer (p<0.05).
      CONCLUSIONS: Modified natural surfactant is an effective treatment option in
      children with ARDS for improving gas exchange, decreasing the use of ventilatory
      support and increasing survival time.

PMID- 14580924
TI  - Hyaluronan blocks human neutrophil elastase (HNE)-induced airway responses in
      sheep.
AB  - Hyaluronan (HA) blocks inhaled porcine pancreatic elastase-induced
      bronchoconstriction in sheep with airway hypersensitivity to Ascaris suum
      antigen. Since elastases from other species may display different catalytic
      properties compared to the human enzyme, we tested the efficacy of HA on human
      neutrophil elastase (HNE)-induced airway responses. We measured pulmonary
      resistance in allergic sheep before and after inhalation of HNE alone and after
      pretreatment with a 150 kD-HA (LKDHA; 3 and 15 mg), or a 300 kD-HA (HKDHA; 6,
      7.5, and 15 mg). HKDHA (3 mg) was given either 0.5, 4, or 8 h before HNE
      challenge; LKDHA (15 mg) and HKDHA (6, 7.5, and 15 mg) were given 8 h before
      challenge. HNE caused an acute bronchoconstriction which was blocked by 3 mg
      LKDHA given 0.5 or 4 h before challenge. LKDHA (3 mg) given 8 h before challenge
      was ineffective, but protection was achieved by increasing the dose to 15 mg.
      When HKDHA at 6, 7.5, and 15 mg was given 8 h before challenge a dose-dependent
      inhibition of the HNE-induced airway response was observed. We conclude that HA
      inhibits HNE-induced airway responses and that within the range of 150-300 kD,
      dose rather than molecular weight may be the most important determinant of
      pretreatment time resulting in a protective effect.

PMID- 14580925
TI  - Efficacy of the novel phosphodiesterase-4 inhibitor BAY 19-8004 on lung function
      and airway inflammation in asthma and chronic obstructive pulmonary disease
      (COPD).
AB  - Selective inhibitors of phosphodiesterase-4 (PDE4) inhibit the hydrolysis of
      intracellular cAMP, which may result in bronchodilation and suppression of
      inflammation. We examined the effect of 1 week treatment with BAY 19-8004 (5 mg
      once daily), a novel orally administered PDE4 inhibitor, on trough FEV1 and
      markers of inflammation in induced sputum in patients with asthma or chronic
      obstructive pulmonary disease (COPD). Seven patients with asthma (mean [SD] FEV1
      69.5 [9.3]% predicted; reversibility in FEV1 26.2 [10.1]%; all non-smokers) and
      11 patients with COPD (FEV1 58.6 [8.3]% predicted; reversibility in FEV1 6.5
      [4.7]%; median [range] 44 [21-90] pack years of smoking) were included in this
      randomized, double-blind, placebo-controlled trial. FEV1 was measured before and
      after 1 week of treatment; sputum was induced by 4.5% saline inhalation on the
      last day of treatment. FEV1 did not improve during either treatment in both
      patient groups (p>0.2). Sputum cell counts were not different following placebo
      and BAY 19-8004 treatment in asthma and COPD patients (p>0.2). However, only in
      patients with COPD, small but significant reductions in sputum levels of albumin
      and eosinophil cationic protein were observed (p<0.05). In conclusion, 1 week of
      treatment with the selective PDE4 inhibitor BAY 19-8004 does not affect FEV1 and
      sputum cell numbers in patients with asthma or COPD. However, such treatment does
      seem to reduce levels of albumin and eosinophil cationic protein in sputum
      samples obtained from patients with COPD.

PMID- 14580926
TI  - Corticosteroid use and its association with microalbuminuria in the adult
      population.
AB  - BACKGROUND: Corticosteroids exhibit a wide range of adverse effects, among which
      are a number of cardiovascular effects. Microalbuminuria shows a strong
      correlation with these cardiovascular effects and is an indicator for
      cardiovascular risk. We now investigate whether use of corticosteroids, either
      systemic or nonsystemic, is associated with microalbuminuria. METHODS: We used
      the data of 7010 subjects of an on-going population based study, focussed on the
      impact of microalbuminuria (PREVEND). Microalbuminuria was defined as urinary
      albumin excretion of 30-300 mg/24 h, measured as the mean of two 24-h urine
      collections. Corticosteroid use was measured in the year preceding the albumin
      measurement using community pharmacy data. RESULTS: After adjusting for age and
      sex, the odds ratio (OR) for having microalbuminuria was slightly elevated (1.21;
      95% CI 1.03-1.41; N=1798) for corticosteroid users. The ORs were lower for
      subjects using only systemic corticosteroids (1.07; 95% CI 0.67-1.72; N=146), or
      only local corticosteroids (1.11; 95% CI 0.93-1.32; N=1442). However, the OR for
      subjects using both systemic and local corticosteroids was raised (1.99; 95% CI
      1.42-2.77; N=210). CONCLUSION: Corticosteroid use, and especially use of both
      systemic and local corticosteroids is associated with microalbuminuria. Based on
      this investigation we cannot say if this is due to adverse effects of
      corticosteroids themselves, or effects of the underlying disease.

PMID- 14580927
TI  - Tolerance to the protective effect of salmeterol in mild untreated asthmatics.
AB  - The aim of this study was to assess the distribution of the occurrence of
      tolerance to the protective effect of salmeterol on allergen challenge in a large
      sample of asthmatic subjects. We investigated 53 subjects (45 male and eight
      female), mean age 24+/-8.2 years, with mild intermittent asthma, in stable phase
      of the disease, never previously treated with regular beta2-agonists. All
      subjects with a previous positive early airway response (EAR) to a screening
      allergen challenge underwent, in double blind randomized, cross-over manner,
      three further allergen challenges: after placebo (T0), after a single dose (50
      microg) of inhaled salmeterol (T1), and after regular treatment with inhaled
      salmeterol (50 microg bid) for 1 week (T2). All subjects showed an EAR after
      placebo treatment (T0), and were completely protected against EAR by the single
      dose of salmeterol (T1). After 1-week regular treatment with salmeterol (T2). 24
      out of 53 subjects (45%) were still protected, whereas 29 subjects (55%) showed a
      significant EAR. The distribution of the response to allergen challenge, which
      was quite homogeneous at T0 and T1, showed considerable heterogeneity at T2.
      Tolerance to the protective effect of salmeterol on allergen challenge can be
      observed in a large group of previously untreated mild asthmatic subjects. This
      phenomenon is heterogeneously distributed, with some subjects still showing a
      complete protection similar to that obtained after a single dose of salmeterol
      and others showing a response similar to that obtained after placebo. The reason
      of this heterogeneity needs to be elucidated.

PMID- 14580928
TI  - Conjugates of ovalbumin and monomethoxypolyethylene glycol abolish late allergic
      responses and decrease IL-4 and IL-5 mRNA expression in the rat.
AB  - The purpose of this study was to test the therapeutic potential of
      monomethoxypolyethylene glycol (mPEG) conjugated-allergen using a rodent model of
      allergic asthma. Previously, this conjugate has been shown to possess the dual
      capacity of inducing long-term ovalbumin (OA)-specific suppression of the
      antibody response and inactivating rat mast cells that have been sensitized with
      murine IgE to OA. Ovalbumin sensitized and challenged Brown Norway rats were
      studied. Fourteen days after sensitization, a test group of six rats received
      mPEG-OA solution intratracheally and were challenged 30 min later with
      aerosolized OA. Another group of seven sensitized rats was similarly challenged
      with OA 30 min after intratracheal administration of normal saline. A group of
      six sensitized rats received mPEG-OA solution intratracheally but were challenged
      with normal saline. Another group of seven sensitized rats received mPEG-BSA
      solution intratracheally and were challenged 30 min later with aerosolized OA. A
      final group of five unsensitized rats were neither challenged nor medicated
      intratracheally. Pulmonary resistance was measured before and for 8 h following
      inhalation challenge. mPEG-OA treatment had an inhibitory effect on the allergic
      late airway response, but the early response was not significantly altered. Both
      mPEG-OA and mPEG-BSA reduced the total cells, eosinophils and neutrophils, in
      bronchoalveolar lavage and decreased the expression of IL-4, IL-5 and IFN-gamma
      mRNA. In conclusion, mPEG-OA can prevent the development of allergen-induced late
      airway responses and reduce airway Th2-type cytokine expression whereas mPEG
      conjugated to an irrelevant antigen (BSA) is anti-inflammatory but does not
      affect the late response.

PMID- 14580931
TI  - Relationship between learning, stress and hippocampal brain-derived neurotrophic
      factor.
AB  - Brain-derived neurotrophic factor (BDNF) expression in the hippocampus is reduced
      in response to acute, as well as repeated immobilization stress. This effect
      might be mediated by corticosterone, because corticosterone administration is
      known to reduce hippocampal BDNF. However, rats subjected to a learning paradigm
      showed an increased BDNF expression in the hippocampus despite the high
      corticosterone levels found during the test. To dissect the relative
      contributions of learning and stress to the overall changes in BDNF levels we set
      up an experimental model in which two groups of rats received the same amount of
      stress, but only one group had the possibility to learn how to avoid it. Using
      this model, we now report that learning and stress exert an opposite modulation
      on BDNF levels in the hippocampus, and that the increasing effect of learning
      predominates over the decreasing effect of stress.

PMID- 14580932
TI  - Neuroadaptive changes in mesocorticolimbic dopamine and acetylcholine neurons
      following cocaine or saline self-administration are dependent on pre-existing
      individual differences.
AB  - Previously, we demonstrated that stress-induced self-grooming behaviour in rats
      predicted an enhanced motivation to self-administer cocaine as determined under a
      progressive ratio schedule of reinforcement. The enhanced motivation of high
      grooming (HG) rats was associated with a reduced reactivity of dopaminergic
      neurons in the medial prefrontal cortex and amygdala, but not nucleus accumbens.
      In the present study, we studied the effect of cocaine and saline self
      administration on these pre-existing differences in neurochemical profile by
      determining the electrically evoked release of [3H]dopamine and
      [14C]acetylcholine from superfused slices of the nucleus accumbens shell and
      core, medial prefrontal cortex and amygdala of HG and low grooming (LG) rats.
      Although HG and LG rats did not differ in acquisition of cocaine and saline self
      administration, both conditions induced substantially different neuroadaptations
      in these rats. Differences in depolarisation-induced dopamine and acetylcholine
      release were maintained in the medial prefrontal cortex, emerged in the nucleus
      accumbens and dissipated in the amygdala. These results indicate that altered
      reactivity of mesocorticolimbic dopaminergic and cholinergic neurons due to
      exposure to cocaine and environmental stimuli (saline) is dependent on pre
      existing neurochemical differences and displays region-specificity. These pre
      existing differences and the cocaine- and environmental-induced neuroadaptations
      seem to act in concert to produce an enhanced motivational state to self
      administer cocaine.

PMID- 14580933
TI  - Estrogen receptor beta in the paraventricular nucleus of hypothalamus regulates
      the neuroendocrine response to stress and is regulated by corticosterone.
AB  - The function of the second nuclear estrogen receptor, estrogen receptor beta
      (ERbeta), in the brain is largely unknown. The present study tested whether 1)
      ERbeta in the paraventricular nucleus (PVN) of the hypothalamus has a direct role
      in the hypothalamic-pituitary-adrenal (HPA) axis-mediated stress function, and 2)
      whether corticosterone (CORT) can regulate ERbeta gene expression in the PVN in
      the intact, cycling female rat. To test the first hypothesis a pure estrogen
      receptor antagonist, ICI182, 780, was microinjected into the PVN bilaterally and
      stress-induced CORT response to an acute stressor (15 min restraint) was measured
      at 0, 15, 30, 60 and 90 min time points. Estrogen antagonist-injected rats showed
      inhibited CORT levels at the peak (15 min) of the stress response compared with
      vehicle-injected animals. To test the second hypothesis, ERbeta mRNA levels were
      measured in the PVN using in situ hybridization histochemistry following sham
      surgery, adrenalectomy, and adrenalectomy with low or high CORT replacement.
      Adrenalectomy reduced ERbeta mRNA expression in the PVN, whereas CORT replacement
      fully reversed this effect in a dose-dependent fashion. Both antagonist
      inhibition of CORT response and CORT-mediated regulation of ERbeta mRNA were
      found to be estrus cycle-dependent in the intact, cycling female. These data
      suggest that ERbeta in the PVN may critically modulate the HPA axis response to
      stress and is, in turn, regulated by circulating CORT.

PMID- 14580934
TI  - Brain-derived neurotrophic factor mRNA downregulation produced by social
      isolation is blocked by intrahippocampal interleukin-1 receptor antagonist.
AB  - Manipulations that increase the expression of the pro-inflammatory cytokine
      interleukin-1beta (IL-1beta) in the hippocampus (e.g. peripheral administration
      of lipopolysaccharide, i.c.v. glycoprotein 120, social isolation) as well as the
      intrahippocampal injection of IL-1beta following a learning experience,
      dramatically impair the memory of that experience if the formation of the memory
      requires the hippocampus. Here we employed social isolation to further study this
      phenomenon, as well as its relation to brain-derived neurotrophic factor (BDNF).
      BDNF was studied because of its well-documented role in the formation of
      hippocampally based memory. A 6 h period of social isolation immediately after
      contextual fear conditioning impaired memory for context fear measured 48 h
      later, and decreased BDNF mRNA in the dentate gyrus and the CA3 region of the
      hippocampus assessed immediately after the isolation. Moreover, an
      intrahippocampal injection of the IL-1 receptor antagonist prior to the isolation
      period prevented both the BDNF downregulation and the memory impairments produced
      by the isolation. These data suggest that hippocampal-dependent memory
      impairments induced by elevated levels of brain IL-1beta may occur via an IL
      1beta-induced downregulation in hippocampal BDNF.

PMID- 14580935
TI  - Orexinergic neurons and barbiturate anesthesia.
AB  - Orexins (OXs) regulate sleep with possible interactions with brain noradrenergic
      neurons. In addition, noradrenergic activity affects barbiturate anesthesia. As
      we have also recently reported that OXs selectively evoke norepinephrine release
      from rat cerebrocortical slices we hypothesized that barbiturate anesthesia may
      result from of an interaction with central orexinergic systems. To test this
      hypothesis, we performed a series of in vivo and in vitro studies in rats. In
      vivo, the effects of i.c.v. OX A, B and SB-334867-A (OX1 receptor antagonist) on
      pentobarbital, thiopental or phenobarbital-induced anesthesia times (loss of
      righting reflex) was assessed. In vitro effects of barbiturates and SB-334867-A
      on OX-evoked norepinephrine release from cerebrocortical slice was examined. In
      Chinese hamster ovary cells expressing human OX1/OX2 receptors OX A- and B-evoked
      increases in intracellular Ca2+ were measured with and without barbiturates. OX A
      and B significantly decreased pentobarbital, thiopental and phenobarbital
      anesthesia times by 15-40%. SB-334867-A increased thiopental-induced anesthesia
      time by approximately by 40%, and reversed the decrease produced by OX A. In
      vitro, all anesthetic barbiturates inhibited OX-evoked norepinephrine release
      with clinically relevant IC50 values. A GABAA antagonist, bicuculline, did not
      modify the inhibitory effects of thiopental and the GABAA agonist, muscimol, did
      not inhibit norepinephrine release. In addition there was no interaction of
      barbiturates with either OX1 or OX2 receptors. Collectively our data suggest that
      orexinergic neurons may be an important target for barbiturates, and GABAA, OX1
      and OX2 receptors may not be involved in this interaction.

PMID- 14580936
TI  - Thymulin reverses inflammatory hyperalgesia and modulates the increased
      concentration of proinflammatory cytokines induced by i.c.v. endotoxin injection.
AB  - The immunomodulatory thymic hormone thymulin has been shown previously to possess
      anti-inflammatory actions in the periphery. In this study, we have examined the
      effect of i.c.v. injections of either endotoxin (ET) or thymulin, in separate
      groups of conscious rats, on pain-related behavior and cytokine levels in
      different areas of the brain. Furthermore, we investigated the effect of
      pretreatment with either i.c.v. or i.p. injections of thymulin on endotoxin
      induced hyperalgesia and the effect of pretreatment with i.c.v. thymulin on
      endotoxin-induced up-regulation of cytokine levels. Our results demonstrate that
      i.c.v. injection of endotoxin (1 microg in 5 microl saline) resulted in a
      significant decrease in the nociceptive thresholds as assessed by different pain
      tests, with peak hyperalgesia at 3 h. However, thymulin at different doses, when
      injected (i.c.v.), had no significant effect on pain related behavior.
      Pretreatment (i.c.v.) with thymulin (0.1, 0.5 and 1 microg in 5 microl saline) 20
      min before endotoxin (i.c.v.) injection (1 microg in 5 microl saline) reduced, in
      a dose dependent manner, the endotoxin-induced hyperalgesia and exerted
      differential effects on the up-regulated levels of cytokines in different areas
      of the brain. The results provide behavioral and immunochemical characterization
      of a rat model for intracerebral inflammation and indicates a neuroprotective
      role for thymulin in the CNS.

PMID- 14580937
TI  - Reduced sodium appetite and increased oxytocin gene expression in mutant mice
      lacking beta-endorphin.
AB  - Central opioid and oxytocinergic systems have been involved in the regulatory
      control of sodium appetite. In addition, previous studies support the existence
      of a functional interaction between opioid peptides and oxytocinergic pathways,
      and suggest that beta-endorphin neurons would modulate the activity of central
      oxytocinergic pathways, its pituitary secretion and sodium appetite. To
      investigate the role of this opioid peptide in the control of oxytocin (OT)
      synthesis and sodium appetite regulation we used mice with gene dosage-dependent
      variations in brain beta-endorphin content, expressing either 100%, 50%, or 0% of
      normal beta-endorphin content. Our results show that beta-endorphin knockout (KO)
      and heterozygous (HT) mutant mice consume approximately a 50% less 2% NaCl
      solution compared with wild type mice (WT), after furosemide and low sodium diet
      treatment. These data suggest that beta-endorphin may facilitate induced sodium
      appetite, giving new evidence about the role of beta-endorphin on sodium appetite
      behavior. Our data also indicate that OT mRNA levels evaluated by in situ
      hybridization significantly increased within the hypothalamic paraventricular
      nucleus of WT animals after induced sodium ingestion, giving support to former
      evidence indicating an inhibitory role for central OT in the control of sodium
      appetite. Moreover, beta-endorphin mutated mice have similar higher levels of OT
      mRNA expression after the different conditions analyzed: basal, control or
      experimental, compared with WT mice. Both control HT and KO mice showed higher OT
      mRNA expression levels than control WT group and these levels did not change
      after induced sodium intake. Taken together, our data suggest that the reduced
      sodium ingestion observed in beta-endorphin deficient mice could be due to a
      higher expression of the OT gene. This conclusion would support the hypothesis
      that OT inhibits sodium intake and provides new evidence about beta-endorphin
      modulation of OT synthesis and sodium appetite.

PMID- 14580938
TI  - Mechanisms and regulation of transferrin and iron transport in a model blood
      brain barrier system.
AB  - For peripheral iron to reach the brain, it must transverse the blood-brain
      barrier. In order for the brain to obtain iron, transferrin receptors are present
      in the vascular endothelial cell to facilitate movement of transferrin bound iron
      into the brain parenchyma. However, a number of significant voids exist in our
      knowledge about transport of iron into the brain. These gaps in our knowledge are
      significant not only because iron is an essential neurotrophic factor but also
      because the system for delivery of iron into the brain is being viewed as an
      opportunity to circumvent the blood-brain barrier for delivery of neurotoxins to
      tumors or trophic factors in neurodegenerative diseases. In this study, we have
      used fluorescein-transferrin-59Fe in a bovine retinal endothelial cell culture
      system to determine the mechanism of transferrin-iron transport and to test the
      hypothesis that the iron status of the endothelial cells would influence iron
      transport. Our results indicated that iron is transported across endothelial
      cells both bound to and not bound to transferrin. The ratio of non-transferrin
      bound iron to transferrin-bound iron transported is dependent upon the iron
      status of the cells. Blocking acidification of endosomes led to a significant
      decrease in transport of non-transferrin-bound iron but not transferrin-bound
      iron. Blocking pinocytosis had no effect on either transferrin or iron
      transcytosis. These results indicate that there is both transferrin-mediated and
      non-transferrin-mediated transcytosis of iron and that the process is influenced
      by the iron status of the cells. These data have considerable implications for
      common neurodegenerative diseases that are associated with excess brain iron
      accumulation and the numerous neurological complications associated with brain
      iron deficiency.

PMID- 14580939
TI  - Group IIA secretory phospholipase A2 stimulates exocytosis and neurotransmitter
      release in pheochromocytoma-12 cells and cultured rat hippocampal neurons.
AB  - Recent evidence shows that secretory phospholipase A2 (sPLA2) may play a role in
      membrane fusion and fission, and may thus affect neurotransmission. The present
      study therefore aimed to elucidate the effects of sPLA2 on vesicle exocytosis.
      External application of group IIA sPLA2 (purified crotoxin subunit B or purified
      human synovial sPLA2) caused an immediate increase in exocytosis and
      neurotransmitter release in pheochromocytoma-12 (PC12) cells, detected by carbon
      fiber electrodes placed near the cells, or by changes in membrane capacitance of
      the cells. EGTA and a specific inhibitor of sPLA2 activity, 12-epi-scalaradial,
      abolished the increase in neurotransmitter release, indicating that the effect of
      sPLA2 was dependent on calcium and sPLA2 enzymatic activity. A similar increase
      in neurotransmitter release was also observed in hippocampal neurons after
      external application of sPLA2, as detected by changes in membrane capacitance of
      the neurons. In contrast to external application, internal application of sPLA2
      to PC12 cells and neurons produced blockade of neurotransmitter release. Our
      recent studies showed high levels of sPLA2 activity in the normal rat
      hippocampus, medulla oblongata and cerebral neocortex. The sPLA2 activity in the
      hippocampus was significantly increased, after kainate-induced neuronal injury.
      The observed effects of sPLA2 on neurotransmitter release in this study may
      therefore have a physiological, as well as a pathological role.

PMID- 14580940
TI  - Identification of human SEP1 as a glial cell line-derived neurotrophic factor
      inducible protein and its expression in the nervous system.
AB  - Glial cell line-derived neurotrophic factor (GDNF) signals through multisubunit
      receptor complex consisting of RET tyrosine kinase and a
      glycosylphosphatidylinositol-anchored coreceptor called GDNF family receptor
      alpha1 (GFRalpha1). In the current study, we cloned a human SEP1 gene as a GDNF
      inducible gene using human neuroblastoma cells that express RET and GFRalpha1.
      The induction of the SEP1 gene showed two peaks at 0.5-2 h and 24-48 h after GDNF
      stimulation by Northern blotting and quantitative real-time reverse transcriptase
      polymerase chain reaction. The late induction was also confirmed at protein
      levels by Western blotting with anti-SEP1 antibody. Immunostaining revealed that
      the expression of the SEP1 protein was detected in cell body, elongated neurites
      and growth cone-like structure of neuroblastoma cells treated with GDNF. In
      addition, we found a high level of SEP1 expression in neurons of the dorsal root
      and superior cervical ganglia and motor neurons of the spinal cord of mice in
      which RET is also expressed. SEP1 was co-immunoprecipitated with alpha- and beta
      tubulins from the lysate of mouse brain. These results thus suggested that SEP1
      is a GDNF-inducible and microtubule-associated protein that may play a role in
      the nervous system.

PMID- 14580941
TI  - Distribution of antinociceptive adenosine A1 receptors in the spinal cord dorsal
      horn, and relationship to primary afferents and neuronal subpopulations.
AB  - Adenosine can reduce pain and allodynia in animals and man, probably via spinal
      adenosine A1 receptors. In the present study, we investigate the distribution of
      the adenosine A1 receptor in the rat spinal cord dorsal horn using
      immunohistochemistry, in situ hybridization, radioligand binding, and confocal
      microscopy. In the lumbar cord dorsal horn, dense immunoreactivity was seen in
      the inner part of lamina II. This was unaltered by dorsal root section or
      thoracic cord hemisection. Confocal microscopy of the dorsal horn revealed close
      anatomical relationships but no or only minor overlap between A1 receptors and
      immunoreactivity for markers associated with primary afferent central endings:
      calcitonin gene-related peptide, or isolectin B4, or with neuronal
      subpopulations: mu-opioid receptor, neuronal nitric oxide synthase, met
      enkephalin, parvalbumin, or protein kinase Cgamma, or with glial cells: glial
      fibrillary acidic protein. A few adenosine A1 receptor positive structures were
      double-labeled with alpha-amino-3-hydroxy-5-methyl-4-isoaxolepropionic acid
      glutamate receptor subunits 1 and 2/3. The results indicate that most of the
      adenosine A1 receptors in the dorsal horn are located in inner lamina II
      postsynaptic neuronal cell bodies and processes whose functional and
      neurochemical identity is so far unknown. Many adenosine A1 receptor positive
      structures are in close contact with isolectin B4 positive C-fiber primary
      afferents and/or postsynaptic structures containing components of importance for
      the modulation of nociceptive information.

PMID- 14580942
TI  - Estradiol prevents amyloid-beta peptide-induced cell death in a cholinergic cell
      line via modulation of a classical estrogen receptor.
AB  - The pathology of Alzheimer's disease includes amyloid-beta peptide aggregation
      that contributes to degeneration of cholinergic neurons. Even though the
      underlying molecular mechanisms remain unclear, recent in vitro evidence supports
      a protective role for estrogens against several neurotoxic agents. Here we report
      that, in a murine cholinergic cell line (SN56), the massive cell death induced by
      1-40 fragment of amyloid-beta peptide was prevented by 17beta-estradiol through a
      mechanism that may involve estrogen receptor activation. The protective effect of
      estradiol was observed in a dose-dependent manner, and was completely blocked by
      the pure antiestrogen ICI 182,780. In contrast, the inactive isomer 17alpha
      estradiol consistently showed weaker neuroprotection than the native hormone that
      was unaffected by ICI 182,780 treatment. In addition, equivalent concentrations
      of 17beta-estradiol enhanced luciferase activity in cells transfected with a
      luciferase reporter gene driven by tandem estrogen response elements. Estrogen
      induced luciferase activity was blocked by ICI 182,780, indicating estrogen
      receptor-dependent transcriptional activity. We also observed by reverse
      transcription-polymerase chain reaction, Western blot and immunocytochemistry
      that increasing concentrations of 17beta-estradiol enhanced the expression of
      estrogen receptor alpha mRNA and protein during amyloid-beta-induced toxicity.
      Under these conditions, it was found by confocal microscopy that the localization
      of estrogen receptor alpha in the absence of hormone was mainly extranuclear.
      However, the receptor was consistently observed also at the nuclear region after
      estrogen exposure. Overall, these data suggest that estrogen may exert
      neuroprotective effects against amyloid-beta-induced toxicity by activation of
      estrogen receptor-mediated pathways. In addition, intracellular estrogen
      receptors are up-regulated by their cognate hormone even during exposure to
      neurotoxic agents.

PMID- 14580943
TI  - beta-estradiol influences differentiation of hippocampal neurons in vitro through
      an estrogen receptor-mediated process.
AB  - We utilized morphometric analysis of 3 day cultures of hippocampal neurons to
      determine the effects of both estradiol and the synthetic estrogen receptor
      modulator raloxifene on several parameters of neuronal growth and
      differentiation. These measurements included survival, neurite production,
      dendrite number, and axon and dendrite length and branching. 17 beta-Estradiol
      (10 nM) selectively stimulated dendrite branching; this effect was neither
      mimicked by alpha-estradiol, nor blocked by the estrogen receptor antagonist ICI
      182780. The selective estrogen receptor modulator raloxifene (100 nM) neither
      mimicked nor reversed the effects of estradiol on dendritic branching. Western
      immunoblotting for the alpha and beta subtypes of estrogen receptor revealed the
      presence of alpha, but not beta, estrogen receptors in our hippocampal cultures.
      There is growing recognition of the effects of 17 beta-estradiol on neuronal
      development and physiology, with implications for brain sexual dimorphism,
      plasticity, cognition, and the maintenance of cognitive function during aging.
      The role of estradiol in hippocampal neuronal differentiation and function has
      particular implications for learning and memory. These data support the
      hypothesis that 17 beta-estradiol is acting via alpha estrogen receptors in
      influencing hippocampal development in vitro. Raloxifene, prescribed to combat
      osteoporosis in post-menopausal women, is a selective estrogen receptor modulator
      with tissue-specific agonist/antagonist properties. Because raloxifene had no
      effect on dendritic branching, we hypothesize that it does not interact with the
      alpha estrogen receptor in this experimental paradigm.

PMID- 14580944
TI  - Molecular characterization of the zebrafish P2X receptor subunit gene family.
AB  - P2X receptors are non-selective cation channels gated by extracellular ATP and
      are encoded by a family of seven subunit genes in mammals. These receptors
      exhibit high permeabilities to calcium and in the mammalian nervous system they
      have been linked to modulation of neurotransmitter release. Previously, three
      complementary DNAs (cDNAs) encoding members of the zebrafish gene family have
      been described. We report here the cloning and characterization of an additional
      six genes of this family. Sequence analysis of all nine genes suggests that six
      are orthologs of mammalian genes, two are paralogs of previously described
      zebrafish subunits, and one remains unclassified. All nine subunits were
      physically mapped onto the zebrafish genome using radiation hybrid analysis. Of
      the nine gene products, seven give functional homo-oligomeric receptors when
      recombinantly expressed in human embryonic kidney cell line 293 cells. In
      addition, these subunits can form hetero-oligomeric receptors with phenotypes
      distinct from the parent subunits. Analysis of gene expression patterns was
      carried out using in situ hybridization, and seven of the nine genes were found
      to be expressed in embryos at 24 and 48 h post-fertilization. Of the seven that
      were expressed, six were present in the nervous system and four of these
      demonstrated considerable overlap in cells present in the sensory nervous system.
      These results suggest that P2X receptors might play a role in the early
      development and/or function of the sensory nervous system in vertebrates.

PMID- 14580946
TI  - Presynaptic delta opioid receptors differentially modulate rhythm and pattern
      generation in the ventral respiratory group of the rat.
AB  - The specific role of the Delta opioid receptor (DOR), in opioid-induced
      respiratory depression in the ventral respiratory group (VRG) is largely unknown.
      Here, we sought to determine (1) the relationship between DOR-immunoreactive (ir)
      boutons, bulbospinal and functionally identified respiratory neurons in the VRG
      and (2) the effects of microinjection of the selective DOR agonist, D-Pen 2,5
      enkephalin (DPDPE), into different subdivisions of the VRG, on phrenic nerve
      discharge and mean arterial pressure. Following injections of retrograde tracer
      into the spinal cord or intracellular labelling of respiratory neurons, in
      Sprague-Dawley rats, brainstem sections were processed for retrograde or
      intracellular labelling and DOR-ir. Bulbospinal neurons were apposed by DOR-ir
      boutons regardless of whether they projected to single (cervical or thoracic
      ventral horn) or multiple (cervical and thoracic ventral horn) targets in the
      spinal cord. In the VRG, a total of 24 +/- 5% (67 +/- 13/223 +/- 49) of neurons
      projecting to the cervical ventral horn, and 37 +/- 3% (96 +/- 22/255 +/- 37) of
      neurons projecting to the thoracic ventral horn, received close appositions from
      DOR-ir boutons. Furthermore, DOR-ir boutons closely apposed six of seven
      intracellularly labelled neurons, whilst the remaining neuron itself possessed
      boutons that were DOR-ir. DPDPE was microinjected (10 mM, 60 nl, unilateral) into
      regions of respiratory field activity in the VRG of anaesthetised, vagotomised
      rats, and the effects on phrenic nerve discharge and mean arterial pressure were
      recorded. DPDPE depressed phrenic nerve amplitude, with little effect on phrenic
      nerve frequency in the Botzinger complex, pre-Botzinger complex and rVRG, the
      greatest effects occurring in the Botzinger complex. The results indicate that
      the DOR is located on afferent inputs to respiratory neurons in the VRG.
      Activation of the DOR in the VRG is likely to inhibit the release of
      neurotransmitters from afferent inputs that modulate the pattern of activity of
      VRG neurons.

PMID- 14580945
TI  - Pentobarbital modulates intrinsic and GABA-receptor conductances in
      thalamocortical inhibition.
AB  - We investigated interactions of an anesthetic barbiturate, pentobarbital, with
      non-ligand gated channels and identified inhibitory synaptic transmission in
      thalamic neurons. Using whole cell voltage-clamp, current-clamp and single
      channel recording techniques in rat ventrobasal neurons of slices and dispersed
      preparations, we determined the mechanisms of pentobarbital actions on ionic
      currents and inhibitory postsynaptic currents (IPSCs), mediated by aminobutyric
      acid (GABA). We investigated pentobarbital effects on intrinsic currents using
      hyperpolarizing voltage commands from rest and tetrodotoxin blockade of action
      potentials. At concentrations near 8 microM, pentobarbital increased input
      conductance and induced net outward current, I(PB), at potentials near action
      potential threshold. The reversal potential of I(PB) was -75 mV, implicating K+
      and other ions. Cs+ (3 mM) which inhibits both K+ currents and inward rectifier
      (Ih), completely blocked IPB, whereas the selective Ih blocker, ZD-7288 (25
      microM), or Ba2+ (2 mM) which suppresses only K+ currents, reduced IPB.
      Pentobarbital inhibited the Ih, consistent with a ZD-7288-induced shift in
      reversal potential for IPB toward K+ equilibrium potential. Pentobarbital
      increased the inward K+ rectifier, IKir, and leak current, Ileak. We determined
      the susceptibility of IPSCs, evoked by reticular stimulation, to antagonism by
      bicuculline, picrotoxinin and 2-hydroxysaclofen and identified their receptor
      subclass components. At EC50 = 53 microM, pentobarbital increased the duration of
      IPSCs. The prolonged IPSC duration during pentobarbital was attributable to
      enhanced open probability of GABAA channels, because combined with GABA,
      pentobarbital application increased mean channel open time without affecting
      channel conductance. At concentrations up to 100 microM, pentobarbital did not
      directly activate GABAA receptors. The concentration-response relationships for
      pentobarbital effects on the intrinsic currents and IPSCs overlapped, implying
      multiple sites of action and possible redundancy in anesthetic mechanisms. This
      is the first study to show that an i.v. anesthetic modulates the intrinsic
      currents, Ih, IKir, and Ileak, as well as IPSC time course in the same neurons.
      These effects likely underlie inhibition in thalamocortical neurons during
      pentobarbital anesthesia.

PMID- 14580947
TI  - Antidepressant drug treatment induces Arc gene expression in the rat brain.
AB  - The mechanism underlying the therapeutic effect of antidepressants is not known
      but neuroadaptive processes akin to long-term potentiation have been postulated.
      Arc (Activity-regulated, cytoskeletal-associated protein) is an effector
      immediate early gene implicated in LTP and other forms of neuroplasticity. Recent
      data show that Arc expression is regulated by brain 5-hydroxytryptamine neurones,
      a target of many antidepressants. Here in situ hybridisation and
      immunohistochemistry were used to examine whether Arc expression in rat brain is
      altered by antidepressant drug treatment. Repeated administration of the
      monoamine reuptake inhibitors paroxetine, venlafaxine or desipramine induced
      region-specific increases in Arc mRNA. These increases were greatest in regions
      of the cortex (frontal and parietal cortex) and hippocampus (CA1 layer) and
      absent in the caudate putamen. Repeated treatment with the monoamine oxidase
      inhibitor, tranylcypromine, increased Arc mRNA in a similar fashion to the
      monoamine reuptake inhibitors. The antidepressant drugs also increased the number
      of Arc-immunoreactive cells in the parietal cortex. Acute antidepressant
      injection, and repeated administration of the antipsychotic drug chlorpromazine,
      produced either limited or no changes in Arc mRNA. The data suggest that chronic
      treatment with antidepressant drugs induces Arc gene expression in specific
      regions across the rat forebrain. Up-regulation of Arc expression may be part of
      the process by which antidepressant drugs achieve long-term changes in synaptic
      function in the brain.

PMID- 14580948
TI  - Inhibition of neuronal nitric oxide synthase-mediated activation of poly(ADP
      ribose) polymerase in traumatic brain injury: neuroprotection by 3
      aminobenzamide.
AB  - Focal traumatic injury to the cerebral cortex is associated with early activation
      of the neuronal isoform of nitric oxide synthase (nNOS), where high
      concentrations of nitric oxide-derived free radicals elicit extensive DNA damage.
      Subsequent activation of the nuclear repair enzyme poly(ADP-ribose) polymerase
      (PARP) causes a severe energy deficit leading to the ultimate demise of affected
      neurons. Little is known about the temporal relationship of nNOS and PARP
      activation and the neuroprotective efficacy of their selective blockade in
      traumatic brain injury. To determine the relationship of nNOS and PARP
      activation, brain injury was induced by cryogenic lesion to the somatosensory
      cortex applying a pre-cooled cylinder after trephination for 6 s to the intact
      dura mater. Pre-treatment with 3-bromo-7-nitroindazole (BrNI; 25 mg/kg, i.p.),
      and pre- or combined pre- and post-treatment with 3-aminobenzamide (AB; 10 mg/kg
      (i.c.v.) or 10 mg/kg/h (i.p.)) were used to inhibit nNOS and PARP, respectively.
      Cold lesion-induced changes in the somatosensory cortex and neuroprotection by
      BrNI and AB were determined using immunocytochemistry and immunodot-blot for
      detection of poly(ADP-ribose; PAR), the end-product of PARP activation, and the
      triphenyltetrazolium-chloride assay to assess lesion volume. PAR immunoreactivity
      reached its peak 30 min post-lesion and was followed by gradual reduction of PAR
      immunolabeling. BrNI pre-treatment significantly decreased the lesion-induced PAR
      concentration in damaged cerebral cortex. Pre-treatment by i.c.v. infusion of AB
      markedly diminished cortical PAR immunoreactivity and significantly reduced the
      lesion volume 24 h post-injury. In contrast, i.p. AB treatment remained largely
      ineffective. In conclusion, our data indicate early activation of PARP after cold
      lesion that is, at least in part, related to nNOS induction and supports the
      relevance of nNOS and/or PARP inhibition to therapeutic approaches of traumatic
      brain injury.

PMID- 14580949
TI  - Dynorphinergic GABA neurons are a target of both typical and atypical
      antipsychotic drugs in the nucleus accumbens shell, central amygdaloid nucleus
      and thalamic central medial nucleus.
AB  - Administration of typical and atypical antipsychotic drugs leads to activation of
      cells in the nucleus accumbens shell, central amygdaloid nucleus, and midline
      thalamic central medial nucleus, implicating important shared effects of these
      drugs. However, the exact cell types responding to antipsychotic drugs in the
      nucleus accumbens shell, central amygdaloid nucleus, and midline thalamic central
      medial nucleus are unclear. We report here that, in a rat model, the results of
      studies using double immunofluorescence labeling with antibodies directed against
      markers specific to candidate cell types suggest that the cells responding to
      haloperidol and clozapine in all three sites are: 1) neurons, rather than
      astrocytes; 2) inhibitory GABA neurons, but not acetylcholinergic neurons; and 3)
      dynorphin-containing GABA neurons, but not M-enkephalin-containing GABA neurons.
      The present study provides pharmacological evidence, at the cellular level in
      vivo, that the shared effects of antipsychotic drugs, whether typical and
      atypical, is activation of dynorphinergic GABA neurons in the nucleus accumbens
      shell, central amygdaloid nucleus, and midline thalamic central medial nucleus.
      Alternative ways to modulate dynorphinergic GABA neuronal activity or its target
      receptors might present an important new avenue for the treatment of
      schizophrenia and other psychotic disorders.

PMID- 14580950
TI  - Heme oxygenase type 2 modulates behavioral and molecular changes during chronic
      exposure to morphine.
AB  - The heme oxygenase (HO) enzyme system has been shown to participate in
      nociceptive signaling in a number of different models of pain. In these
      experiments we investigated the role of the HO type 2 (HO-2) isozyme in tolerance
      to the analgesic effects of morphine, and the hyperalgesia and allodynia which
      are measurable upon cessation of administration. Wild type C57Bl/6 wild type mice
      or HO-2 null mutants in that background strain were treated with morphine for 5
      days. The morphine administration protocol consisted of either twice daily
      repeated s.c. boluses of 15 mg/kg or s.c. implantation of a morphine pellet. At
      the end of the treatment period wild type mice treated by either protocol
      exhibited tolerance, but the HO-2 null mutants did not. The HO-2 null mutants
      also exhibited less mechanical allodynia following cessation of morphine
      administration, though only modest differences in thermal hyperalgesia were
      noted. There was no correlation between the degree of tolerance obtained in the
      bolus and pellet protocols and the degree of hyperalgesia and allodynia observed
      after cessation of morphine administration in the wild type mice. Our final
      experiments analyzed increases in expression of mRNA for nitric oxide synthase
      type 1, N-methyl-D-aspartate (NMDA) receptor NMDAR1 subunit and prodynorphin in
      spinal cord tissue. In pellet-treated mice two- to three-fold increases were
      observed in the abundance of these species, but very little change was observed
      in the null-mutant mice. Taken together our results indicate that HO-2
      participates in the acquisition of opioid tolerance, the expression of mechanical
      allodynia after cessation of opioid administration and in gene regulation
      occurring in the setting of treatment with morphine. Furthermore, these studies
      suggest that the mechanisms underlying analgesic tolerance and opioid-induced
      hypersensitivity are at least somewhat distinct.

PMID- 14580951
TI  - Altered temporal pattern of mechanically evoked C-fiber activity in a model of
      diabetic neuropathy in the rat.
AB  - While enhanced nociceptor activity has been demonstrated in models of painful
      peripheral neuropathy, analyses of activity pattern, which could play a role in
      the symptoms experienced as well as help elucidate underlying mechanism, are
      still limited. We evaluated the pattern of C-fiber activity, in response to
      mechanical and chemical stimuli, in a rat model of diabetes induced by a
      pancreatic beta-cell toxin, streptozotocin (STZ). In diabetic rats the number of
      action potentials produced by threshold and suprathreshold (10 g) sustained (60
      s) mechanical stimuli was elevated in approximately half of C-fibers. These high
      firing C-fibers demonstrated a disproportionate increase in interspike intervals
      (ISIs) between 100 and 199 ms, compared with low-firing diabetic and control C
      fibers. The co-efficient of variability (CV2), a frequency independent measure of
      ISI variability, was also greater in high-firing fibers, compared with control
      fibers. Unexpectedly, instantaneous frequency of the initial burst of activity
      during the first second was lower in high-firing fibers, even though the average
      frequency over the last 59 s was significantly higher. The number of action
      potentials evoked by a noxious chemical stimulus, 300 and 600 mM KCl, injected
      adjacent to the mechanical receptive field was also significantly increased in C
      fibers from diabetic rats and mechanically high-firing fibers had more action
      potentials in response to KCl than control fibers and a disproportionate increase
      in ISIs between 100 and 199 ms for responses to chemical stimuli appeared only in
      mechanically high-firing C-fibers, compared with the mechanically low-firing
      diabetic or control C-fibers. There was, however, no corresponding change in CV2
      or instantaneous frequency plots for the response to chemical stimulation in
      mechanically high-firing fibers, as there was in the response to mechanical
      stimulation. Our data demonstrate specific changes in firing pattern of high
      firing C-fibers in the rat model of painful neuropathy produced by STZ-diabetes
      that might contribute to the symptoms experienced by patients.

PMID- 14580952
TI  - Perforant path activation of ectopic granule cells that are born after
      pilocarpine-induced seizures.
AB  - Granule cells in the dentate gyrus are born throughout life, and various stimuli
      can affect their development in the adult brain. Following seizures, for
      instance, neurogenesis increases greatly, and some new cells migrate to abnormal
      (ectopic) locations, such as the hilus. Previous electrophysiological studies of
      this population have shown that they have intrinsic properties that are similar
      to normal granule cells, but differ in other characteristics, consistent with
      abnormal integration into host circuitry. To characterize the response of ectopic
      hilar granule cells to perforant path stimulation, intracellular recordings were
      made in hippocampal slices from rats that had pilocarpine-induced status
      epilepticus and subsequent spontaneous recurrent seizures. Comparisons were made
      with granule cells located in the granule cell layer of both pilocarpine- and
      saline-treated animals. In addition, a few ectopic hilar granule cells were
      sampled from saline-treated rats. Remarkably, hilar granule cells displayed
      robust responses, even when their dendrites were not present within the molecular
      layer, where perforant path axons normally terminate. The evoked responses of
      hilar granule cells were similar in several ways to those of normally positioned
      granule cells, but there were some differences. For example, there was an
      unusually long latency to onset of responses evoked in many hilar granule cells,
      especially those without molecular layer dendrites. Presumably this is due to
      polysynaptic activation by the perforant path. These results indicate that
      synaptic reorganization after seizures can lead to robust activation of newly
      born hilar granule cells by the perforant path, even when their dendrites are not
      in the terminal field of the perforant path. Additionally, the fact that these
      cells can be found in normal tissue and develop similar synaptic responses,
      suggests that seizures, while not necessary for their formation, strongly promote
      their generation and the development of associated circuits, potentially
      contributing to a lowered seizure threshold.

PMID- 14580953
TI  - Persistent regional increases in brain-derived neurotrophic factor in the
      flurothyl model of epileptogenesis are dependent upon the kindling status of the
      animal.
AB  - Brain-derived neurotrophic factor (BDNF) appears to be both regulated by and a
      regulator of epileptogenesis. In the flurothyl (HFE) model of kindling mice
      exposed to successive flurothyl trials over 8 days express a rapid, long-lasting
      reduction in generalized seizure threshold and a more slowly evolving change in
      seizure phenotype in response to subsequent flurothyl exposure. The BDNF genotype
      of particular mouse strains appears to influence the epileptogenic progression in
      this model. Thus, we hypothesized that BDNF signaling pathways are altered by
      flurothyl-induced seizures. Following HFE kindling, fully kindled (eight
      seizures) adult male C57BI/6J mice had significantly elevated whole brain BDNF
      levels through at least 28 days after their final seizure. Mice that received
      only four HFE seizures (not kindled) had elevated BDNF levels, but only at 1 day
      post-seizure (DPSz), while BDNF levels were not significantly altered in mice
      receiving just one HFE seizure at any time point studied. Regional expression
      patterns of BDNF in the hippocampus, hypothalamus, and frontal cortex were also
      elevated by one DPSz and returned to control values by 14 DPSz in mice that
      received four HFE seizures. No changes were seen in the cerebellum, striatum, or
      piriform cortex. In contrast, fully kindled mice had significantly elevated BDNF
      levels within the hippocampus, hypothalamus, neocortex, and striatum that
      remained elevated through at least 14 DPSz, while levels were unchanged in the
      cerebellum and piriform cortex. Regional results were confirmed using anti-BDNF
      immunohistochemistry (IHC). Despite changes in BDNF levels following HFE
      kindling, we were unable to demonstrate alterations either in full-length
      tyrosine kinase receptor B (TrkB) expression (Western blot and IHC) or in
      truncated TrkB (IHC) expression levels. Together, these data suggest a model of a
      positive feedback loop involving seizure activity and seizure number and
      persistently modified BDNF signaling pathways that influences seizure phenotypes
      within the HFE kindling paradigm. Thus, long-term elevations in BDNF may be
      responsible in part for epileptogenic processes and the development of human
      refractory epilepsies.

PMID- 14580954
TI  - Spindle and slow wave rhythms at slow wave sleep transitions are linked to strong
      shifts in the cortical direct current potential.
AB  - Electroencephalographic activity at the transition from wakefulness to sleep is
      characterized by the appearance of spindles (12-15 Hz) and slow wave rhythms
      including delta activity (1-4 Hz) and slow oscillations (0.2-1 Hz). While these
      rhythms originate within neocortico-thalamic circuitry, their emergence during
      the passage into slow wave sleep (SWS) critically depends on the activity of
      neuromodulatory systems. Here, we examined the temporal relationships between
      these electroencephalogram rhythms and the direct current (DC) potential recorded
      from the scalp in healthy men (n=10) using cross-correlation analyses. Analyses
      focused on transitions from wakefulness to SWS in the beginning of the sleep
      period, and from SWS to lighter sleep and rapid eye movement (REM) sleep at the
      end of the first sleep cycle. For spindle, delta and slow oscillatory activity
      strong negative correlations with the DC potential were found at the transition
      into SWS with peak correlation coefficients (at zero time lag) averaging r=-0.81,
      -0.88 and -0.88, respectively (P<0.001). Though slightly lower, distinct negative
      correlations between these measures were also found at the transition from SWS to
      REM sleep (-0.78, -0.77 and -0.77, respectively, P<0.001). Fast oscillatory
      activity in the beta frequency band (15-25 Hz) was correlated positively with the
      DC potential (r=+0.75, P<0.05, at the passage to SWS). Data indicate close links
      between increasing spindle, delta and slow oscillatory activity and the
      occurrence of a steep surface negative cortical DC potential shift during the
      transition from wake to SWS. Likewise, a DC potential shift toward surface
      positivity accompanies the disappearance of these oscillatory phenomena at the
      end of the non-REM sleep period. The DC potential shifts may reflect gradual
      changes in extracellular ionic (Ca2+) concentration resulting from the generation
      of spindle and slow wave rhythms, or influences of neuromodulating systems on
      cortical excitability thereby controlling the emergence of cortical spindle and
      slow wave rhythms at SWS transitions.

PMID- 14580955
TI  - Brain serotonin blockade and paradoxical salt intake in rats.
AB  - Serotonin antagonism in the lateral parabrachial nucleus (LPBN) enhances sodium
      appetite induced by hypovolaemia and angiotensin-mineralocorticoid activation,
      but produces no sodium intake in euhydrated animals. In the present work, male
      adult rats (n=21) that received bilateral injections of the serotonergic
      antagonist methysergide (4 microg/0.2 microl) into the LPBN combined to
      intragastric load of 2 M NaCl (2 ml/rat), ingested hypertonic NaCl (ingestion of
      4.3 +/- 1.6 ml/2 h of 0.3 M NaCl versus vehicle into LPBN: 0.2 +/- 0.2 ml/2 h,
      P<0.05). Methysergide- and vehicle-treated animals also ingested water (9.5 +/-
      0.7 and 7.2+/-0.5 ml/2 h, respectively, P>0.05) as expected from the state of
      cell dehydration produced by the load. Ingestion of water (11.0 +/- 1.2 ml/2 h),
      and of 0.3 M NaCl (1.1 +/- 0.7 ml/2 h) were not altered by methysergide in NaCl
      loaded rats with misplaced LPBN injections (n=15).The ingestion of hypertonic
      NaCl by rats with serotonergic blockade in the LPBN suggests that the circuits
      subserving sodium appetite are activated, but at the same time strongly inhibited
      through the LPBN, during cell dehydration.

PMID- 14580956
TI  - Changes in the brain kappa-opioid receptor levels of rats in withdrawal from
      physical dependence upon butorphanol.
AB  - Changes in kappa-opioid receptor levels have been implicated in the development
      of physical dependence upon and withdrawal from the mixed agonist-antagonist
      opioid, butorphanol. Immunoblotting analysis was performed to determine the
      levels of kappa- and mu-opioid receptors in brain regions of rats in withdrawal
      from dependence upon butorphanol or morphine. Physical dependence was induced by
      a 72 h i.c.v. infusion with either butorphanol or morphine (26 nmol/microl/h).
      Withdrawal was subsequently precipitated by i.c.v. challenge with naloxone (48
      nmol/5 microl/rat), administered 2 h following cessation of butorphanol or
      morphine infusion. Immunoblotting analysis of kappa-opioid receptors from
      butorphanol-withdrawal rats showed significant increases in 11 of 21 brain
      regions examined, including the nucleus accumbens, amygdala, dorsomedial
      hypothalamus, hypothalamus, paraventricular thalamus, thalamus, presubiculum, and
      locus coeruleus, when compared with saline treated, non-dependent controls. In
      addition, significant reductions were found in the hippocampus and in cortical
      brain regions, including the parietal cortex and temporal cortex from butorphanol
      withdrawal rats. These findings contrasted with those from morphine-withdrawal
      rats, in which the only changes noted were increases in the thalamus and
      paraventricular thalamus. Changes in the levels of the mu-opioid receptor protein
      were observed in 11 of 21 brain regions examined in morphine-withdrawal rats, but
      only in three of 21 in butorphanol-withdrawal rats. These results implicate a
      substantive and largely unique role for kappa-opioid receptors in mediation of
      the development of physical dependence upon, and the expression of withdrawal
      from, butorphanol, as opposed to the prototypical opioid analgesic, morphine.

PMID- 14580957
TI  - Drugs for the control of parasitic diseases: current status and development.

PMID- 14580958
TI  - Antimalarial chemotherapy: young guns or back to the future?

PMID- 14580959
TI  - Chemotherapy of human African trypanosomiasis: current and future prospects.

PMID- 14580960
TI  - Specific chemotherapy of Chagas disease: controversies and advances.

PMID- 14580961
TI  - Leishmaniasis--current chemotherapy and recent advances in the search for novel
      drugs.

PMID- 14580962
TI  - Drugs for the control of parasitic diseases: current status and development in
      schistosomiasis.

PMID- 14580963
TI  - Mass drug treatment for lymphatic filariasis and onchocerciasis.

PMID- 14580964
TI  - Therapy of intestinal protozoa.

PMID- 14580966
TI  - Drug resistance in parasites: can we stay ahead of the evolutionary curve?

PMID- 14580965
TI  - Human gastrointestinal helminth infections: are they now neglected diseases?

PMID- 14580967
TI  - Functional genomics: identifying drug targets for parasitic diseases.

PMID- 14580968
TI  - Planktonic or biofilm growth affects survival, hydrophobicity and protein
      expression patterns of a pathogenic Campylobacter jejuni strain.
AB  - The effect of planktonic or biofilm modes of growth on survival, hydrophobicity
      and cellular protein expression patterns of a pathogenic Campylobacter jejuni
      strain were determined. This was achieved by growing the strain in brain heart
      infusion broth (with 1% yeast extract), or attached to glass beads in the same
      medium, at 37 degrees C for 48 h under microaerophilic conditions. Cells from the
      broth or the bead surfaces were stored at different temperatures (4, 10, 25 and
      37 degrees C) for 28 days in phosphate buffered saline (PBS) and monitored at
      appropriate time intervals for culturable numbers and hydrophobicity by standard
      methods. In addition, cells were inoculated onto the surface of two processed
      meat products (a bologna and a summer sausage) vacuum packaged and stored at 4
      degrees C for 28 days. Numbers of culturable cells were monitored at appropriate
      time intervals by standard methods. Cells from the broth or the bead surfaces
      were also examined for protein expression using two-dimensional protein
      electrophoresis. Results indicated that numbers of culturable cells in phosphate
      buffered saline decreased from approximately 6 log colony forming units (cfu) g(
      1) to undetectable levels within 14-day storage in a temperature dependent
      manner. Hydrophobicity of broth grown cells decreased from 15% to 0% adherence to
      xylene over the same time in a temperature independent manner. Cells grown in a
      biofilm mode initially displayed a <0.3% adherence to xylene which was maintained
      during storage. Furthermore, cells grown in the biofilm mode decreased in number
      more rapidly on storage in buffer than their counterparts grown in broth. Numbers
      of culturable cells on meat decreased from approximately 5 log cfu g(-1) to
      undetectable levels within 14-day storage in a product dependent manner, with the
      most rapid decrease observed for the more acidic summer sausage. Cells grown in a
      biofilm mode decreased in number more rapidly on storage than broth grown cells.
      The protein expression patterns differed between planktonic and biofilm cells
      with seven unique and 12 up-regulated protein spots expressed in a growth mode
      specific manner. A number of the differentially expressed spots were tentatively
      identified, by comparison to existing literature, as surface- and stress
      associated proteins. Despite the elicitation of some putative stress proteins,
      this study importantly indicates that biofilm cells of C. jejuni are less
      resistant to stress than their planktonic counterparts and may lack a
      sophisticated adaptive stress-resistance response. These findings have
      implication in determining the risks of infection associated with C. jejuni
      contamination on food.

PMID- 14580969
TI  - Characterization of resistance patterns and detection of apramycin resistance
      genes in Escherichia coli isolated from swine exposed to various environmental
      conditions.
AB  - Weaned pigs were separated into eight treatments including a control without
      exposure to apramycin; a control with exposure to apramycin; and apramycin plus
      either cold stress, heat stress, overcrowding, intermingling, poor sanitation, or
      intervention with oxytetracycline, to determine the effects of management and
      environmental conditions on antibiotic resistance among indigenous Escherichia
      coli. Pigs exposed to apramycin sulfate received that antibiotic in the feed at a
      concentration of 150 g/ton for 14 days. Environmental treatments were applied 5
      days following initial antibiotic administration and maintained throughout the
      study. Fecal samples were obtained on day 0 (prior to antibiotic treatment) and
      on days 2, 7, 14, 28, 64, 148, and 149. E. coli were isolated and tested for
      resistance to apramycin using a minimum inhibitory concentration (MIC) broth
      microdilution method. Macrorestriction profiling, arbitrarily primed PCR, PCR
      targeting a gene coding for apramycin resistance, and DNA hybridization were used
      to characterize genetic elements of resistance. Increased (P<0.0001) resistance
      to apramycin was noted in E. coli from all treatment groups administered
      apramycin. MICs of isolates from control pigs receiving apramycin returned to
      pretreatment levels following removal of the antibiotic, whereas isolates from
      cold stress, overcrowding, and oxytetracycline groups expressed greater (P<0.05)
      MICs through day 64, before returning to pretreatment levels. Genetic analysis
      indicated that all resistant isolates carried the aac(3)IV gene sequence and this
      sequence was found in a variety of E. coli isotypes. Our data indicate that E.
      coli resistance to apramycin is increased upon exposure to various stressors.

PMID- 14580970
TI  - Use of redox potential modification by gas improves microbial quality, color
      retention, and ascorbic acid stability of pasteurized orange juice.
AB  - The aim of this paper was to study the effect of both redox potential (Eh) and
      pasteurization of orange juice on stability of color and ascorbic acid, and
      growth recovery of microorganisms during storage at 15 degrees C for 7 weeks.
      Three conditions of Eh, +360 mV (ungassed), +240 mV (gassed with N2), and -180 mV
      (gassed with N2-H2) were applied to orange juice. Both thermal destruction and
      recovery of sublethally heat-injured cells of Lactobacillus plantarum and
      Saccharomyces cerevisiae were investigated. While oxidizing conditions were the
      most effective for thermal destruction of L. plantarum and S. cerevisiae,
      reducing conditions decreased recovery of heated cells of S. cerevisiae. In
      addition, gassing the juice with N2 or N2-H2 increased color retention and
      ascorbic acid stability. The present study demonstrated that juice must be
      reduced just after the heat treatment in order, firstly, to maximize microbial
      destruction during pasteurization, and secondly, to prevent the development of
      microorganisms and stabilize color and ascorbic acid during storage.

PMID- 14580971
TI  - Retention of virulence in viable but non-culturable halophilic Vibrio spp.
AB  - The viable but non-culturable (VBNC) forms of two environmental strains of Vibrio
      alginolyticus 1 and Vibrio parahaemolyticus 66 and one strain of V.
      parahaemolyticus ATCC 43996 showing virulence characteristics (hemolysin
      production, adhesive and/or cytotoxic ability, in vivo enteropathogenicity) were
      obtained by culturing bacteria in a microcosm consisting of artificial sea water
      (ASW) and incubating at 5 degrees C with shaking. Every 2 days, culturability of
      the cells in the microcosm was monitored by spread plates on BHI agar and total
      count and the percentage of viable cells were determined by double staining with
      DAPI and CTC. When cell growth was not detectable (<0.1 CFU/ml), the population
      was considered non-culturable and, then, the VBNC forms were resuscitated in a
      murine model. For each strain, eight male Balb/C mice were intragastrically
      inoculated with 0.1 ml of concentrated ASW bacterial culture. Two mice from each
      group were sacrificed at 2, 4, 8, and 12 days after challenge for autopsy and re
      isolation of the microorganisms from the intestinal tissue cultures. Isolation
      was obtained in 25% of the animals challenged with the VBNC V. alginolyticus
      strain, in 37.5% of those challenged with the VBNC V. parahaemolyticus strain of
      environmental origin and in 50% of the animals infected with VBNC V.
      parahaemolyticus ATCC 43996. The strains thus isolated were again subjected to
      biological assays to determine the retention of pathogenicity. The virulence
      characteristics that seemed to disappear after resuscitation in the mouse were
      subsequently reactivated by means of two consecutive passages of the strains in
      the rat ileal loop model. The results obtained indicate that VBNC forms of the
      strains examined can be resuscitated and retain their virulence properties.

PMID- 14580972
TI  - Antimicrobial interactions of microbial species involved in the fermentation of
      cassava dough into agbelima with particular reference to the inhibitory effect of
      lactic acid bacteria on enteric pathogens.
AB  - Lactic acid bacteria, Bacillus species and yeasts are involved in the
      fermentation of cassava dough into agbelima. Microbial interactions within and
      between these groups of microorganisms were investigated in addition to the
      survival of five enteric pathogens inoculated into agbelima under various
      conditions. Nine out of 10 cultures of lactic acid bacteria isolated at the end
      of agbelima fermentation showed inhibitory effect against 10 cultures of lactic
      acid bacteria isolated at the start of fermentation. Only 3 out of 10 isolates of
      Bacillus subtilis were inhibited by 10 isolates of lactic acid bacteria tested.
      No interactions were observed between yeasts and the lactic acid bacteria,
      whereas three of the Bacillus isolates showed inhibitory effects against the
      yeasts. Twelve isolates of Lactobacillus plantarum tested inhibited the growth of
      an isolate each of Lactobacillus fermentum and Lactobacillus brevis but none
      tested positive for bacteriocin production. The antimicrobial effect of the
      lactic acid bacteria was attributed to acid production. In fermenting cassava
      dough, enteric pathogens survived to different extents depending on pH and their
      sensitivity to acids. Vibrio cholerae C-230, Salmonella typhimurium 9 and
      Salmonella enteritidis 226 were not detectable in 10 g of sample after 4 h when
      inoculated into the 48-h fermented product, agbelima, whereas Shigella
      dysenteriae 2357T and Escherichia coli D2188 were detectable up to 8 h in the
      product.

PMID- 14580973
TI  - Effect of acid adaptation on inactivation of Salmonella during drying and storage
      of beef jerky treated with marinades.
AB  - This study evaluated the influence of pre-drying marinade treatments on
      inactivation of acid-adapted or nonadapted Salmonella on beef jerky during
      preparation, drying and storage. The inoculated (five-strain composite, 6.0 log
      CFU/cm2) slices were subjected to the following marinades (24 h, 4 degrees C)
      prior to drying at 60 degrees C for 10 h and aerobic storage at 25 degrees C for
      60 days: (1) no marinade, control (C), (2) traditional marinade (TM), (3) double
      amount of TM modified with added 1.2% sodium lactate, 9% acetic acid, and 68% soy
      sauce with 5% ethanol (MM), (4) dipping into 5% acetic acid and then TM (AATM),
      and (5) dipping into 1% Tween 20 and then into 5% acetic acid, followed by TM
      (TWTM). Bacterial survivors were determined on tryptic soy agar with 0.1%
      pyruvate and xylose-lysine-tergitol 4 (XLT4) agar. Results indicated that drying
      reduced bacterial populations in the order of pre-drying treatments TWTM (4.8-6.0
      log CFU/cm2)> or =AATM> or =MM>TM> or =C (2.6-5.0 log CFU/cm2). Nonadapted
      Salmonella were significantly (P<0.05) more resistant to inactivation during
      drying than acid-adapted Salmonella in all treatments. Bacterial populations
      decreased below the detection limit (-0.4 log CFU/cm2) as early as 7 h during
      drying or remained detectable even after 60 days of storage, depending on acid
      adaptation, pre-drying treatment, and agar media. The results indicated that acid
      adaptation may not cause increased resistance of Salmonella to the microbial
      hurdles involved in jerky processing and that use of modified marinades in
      manufacturing jerky may improve the effectiveness of drying in inactivating
      Salmonella.

PMID- 14580974
TI  - Growth of Lactobacillus paracasei ssp. paracasei on tofu whey.
AB  - The liquid by-product of the soybean product tofu, tofu whey (TW), was used as a
      growth medium for the production of Lactobacillus paracasei ssp. paracasei LG3
      cultures. The TW used in this study contained stachyose, raffinose, sucrose,
      fructose and glucose, but the strain used could only utilize the three latter.
      The lactobacilli population obtained in MRS broth was three times higher than
      that in TW alone, and supplementation of TW was thus examined. Of 19 mixtures of
      yeast extracts (YE), peptones and potato extracts examined, the best nitrogen
      sources were YE and tryptone. The addition of YE, salts (phosphates, citrates, Mg
      and Mn), glucose as well as Tween to TW tripled the populations to 2.9 x 10(9)
      cfu/ml, which was as high as that obtained in MRS broth. Growth of L. paracasei
      LG3 in cow rehydrated skim milk was inferior to that in TW.

PMID- 14580975
TI  - Inhibition of Listeria monocytogenes by bovicin HC5, a bacteriocin produced by
      Streptococcus bovis HC5.
AB  - Cattle can be infected with Listeria monocytogenes by consuming contaminated
      plant materials, soil or silage, and farmers have sought ways of preventing this
      contamination. Recent work indicated that Streptococcus bovis HC5 produced a
      bacteriocin (bovicin HC5) that could inhibit a variety of gram-positive bacteria,
      and we examined the ability of bovicin HC5 to inhibit 10 strains of L.
      monocytogenes that had been isolated from plant materials, soil, silage and
      infected cattle. Growth experiments indicated that all of the L. monocytogenes
      strains were inhibited by 100 activity units (AU) of bovicin HC5 ml(-1). L.
      monocytogenes cultures that were transferred with sublethal doses (12.5 AU ml(
      1)) could be adapted in stepwise fashion to higher doses of bovicin HC5. However,
      even 'adapted' cultures did not grow if 400 AU ml(-1) was added. The effect of
      bovicin HC5 on L. monocytogenes was bactericidal, and viability decreased 5-7
      logs after only 2 h of exposure. Bovicin HC5 caused a nearly complete efflux of
      intracellular potassium in 15 min but only if the pH was less than 6.0. When the
      pH was greater than 6.0, the cells maintained their potassium pool. L.
      monocytogenes cells that were acid-adapted (final pH of 4.6) were as sensitive to
      bovicin HC5 as those that were not acid-adapted (final pH of 6.3). These results
      support the idea that bovicin HC5 could be effective in controlling listeria in
      contaminated silages.

PMID- 14580978
TI  - Quality control of Aspergillus flavus and A. parasiticus agar and comparison with
      dichloran 18% glycerol agar: a collaborative study.
AB  - AFPA culture medium, which is used for recognition of Aspergillus flavus and A.
      parasiticus, has been validated in a collaborative study including nine
      laboratories located in Australia, Brazil, Denmark, The Netherlands, Sweden and
      United Kingdom. Three freeze-dried fungal mixtures, containing A. flavus/A.
      parasiticus and background fungi, were produced and checked for homogeneity. The
      coefficients of variance were low, ranging from 0.81% to 1.09% for total fungal
      counts and between 2.50% and 2.72% for counts of A. flavus/A. parasiticus. The
      laboratories analysed the contents of two vials of each mixture on commercial A.
      flavus and A. parasiticus agar (AFPA), in-house-made AFPA, and on a standard
      media, dichloran 18% glycerol agar (DG18). Reproducibility values for counts of
      A. flavus/A. parasiticus indicated no differences between the commercial AFPA and
      the in-house-made AFPA. Variation between laboratories was low, indicating that
      the medium was effective in use. Reproducibility values for DG18 were higher.
      There were no differences in counts of A. flavus/A. parasiticus on AFPA and DG18.
      However, DG18 gave slightly higher total fungal counts compared to AFPA.

PMID- 14580976
TI  - Improvement of organoleptic quality of retted cassava products by alkali
      pretreatment of roots and addition of sodium nitrate during retting.
AB  - Alkali pretreatment of cassava roots before retting and addition of sodium
      nitrate during retting were used to manipulate the metabolism of microorganisms
      involved in cassava (Manihot esculenta Crantz) retting, as a method for removing
      the characteristic offensive odour of retted cassava products. Odour was assessed
      by organoleptic methods. The characteristics of fermentation of cassava by the
      traditional method (control) were as follows; aerobic mesophilic count (APC) on
      nutrient agar (NA) at 30 degrees C/48 h, attained a maximum of 2.3 x 10(7)/ml
      retting juice while counts on de Man Rogosa and Sharpe agar (MRS) at 30 degrees
      C/48 h were 1.6 x 10(8)/ml. Maximum titrable acidity was 0.062% lactic acid by
      weight of retting juice. Cassava was retted in 3 days and the product exhibited
      characteristic offensive odour. Addition of NaNO3 into retting water effectively
      removed odour at a concentration of 0.3 g/l. Maximum APC on NA/30 degrees C/48 h
      was 6.8 x 10(6)/ml. Counts on MRS/30 degrees C/48 h exceeded 2.4 x 10(9)/ml.
      Retting was complete in 3 days with a final titrable acidity of 0.068% of retting
      juice. Removal of odour likely resulted from selection of homo-fermentative
      lactic acid bacteria, thus producing mostly odourless lactic acid. Alkali
      pretreatment of roots before retting was efficacious in removing odour at a
      concentration of 10 g/l for 30 min. This fermentation was characterized by APC on
      NA/30 degrees C/48 h of 5.4 x 10(6)/ml; MRS/30 degrees C/48 h reached a maximum
      of only 10 x 10(4)/ml and correspondingly low titrable acidity of 0.003%. Low
      counts of lactic acid bacteria correlate well with the absence of odour in this
      sample. Both treatments did not adversely affect the detoxification process,
      yielding "foo-foo" with HCN levels lower than 10 mg/kg. Residual nitrates and
      nitrites of 30 mg/kg in the sodium nitrate-treated sample were also within the
      safe limits of 156 mg/kg allowed in many countries. Organoleptically improved
      samples were acceptable to the public.

PMID- 14580980
TI  - Locking Compression Plate.

PMID- 14580979
TI  - Backgrounds of the technology of internal fixators.

PMID- 14580981
TI  - Development of the Locking Compression Plate.
AB  - The development of the Locking Compression Plate (LCP) reflects the multilateral
      collaboration of clinicians, researchers, developers and industry. In retrospect,
      combining two completely different anchorage technologies into one implant is
      logical and the practical solution is simple. The clinical instructions for the
      new implant, which severely limited the constructive scope, proved to be critical
      for the project. Unlike an independent new development, compatibility with
      existing surgical techniques, instruments and implants had to be maintained.
      Industrial implementation of the LCP is only possible with the use of state-of
      the-art production centres with up to five computer-controlled axes. The
      unlimited possibility of using the LCP as a compression plate, an internal
      fixator or in a specific combination allows ideal plate anchorage that is adapted
      to the bone. Combined with minimally invasive implant technology (MIPO), the
      indication spectrum of plate osteosynthesis can be expanded in a meaningful
      manner.

PMID- 14580982
TI  - Biomechanical testing of the LCP--how can stability in locked internal fixators
      be controlled?
AB  - New plating techniques, such as non-contact plates, have been introduced in
      acknowledgment of the importance of biological factors in internal fixation.
      Knowledge of the fixation stability provided by these new plates is very limited
      and clarification is still necessary to determine how the mechanical stability,
      e.g. fracture motion, and the risk of implant failure can best be controlled. The
      results of a study based on in vitro experiments with composite bone cylinders
      and finite element analysis using the Locking Compression Plate (LCP) for
      diaphyseal fractures are presented and recommendations for clinical practice are
      given. Several factors were shown to influence stability both in compression and
      torsion. Axial stiffness and torsional rigidity was mainly influenced by the
      working length, e.g. the distance of the first screw to the fracture site. By
      omitting one screw hole on either side of the fracture, the construct became
      almost twice as flexible in both compression and torsion. The number of screws
      also significantly affected the stability, however, more than three screws per
      fragment did little to increase axial stiffness; nor did four screws increase
      torsional rigidity. The position of the third screw in the fragment significantly
      affected axial stiffness, but not torsional rigidity. The closer an additional
      screw is positioned towards the fracture gap, the stiffer the construct becomes
      under compression. The rigidity under torsional load was determined by the number
      of screws only. Another factor affecting construct stability was the distance of
      the plate to the bone. Increasing this distance resulted in decreased construct
      stability. Finally, a shorter plate with an equal number of screws caused a
      reduction in axial stiffness but not in torsional rigidity. Static compression
      tests showed that increasing the working length, e.g. omitting the screws
      immediately adjacent to the fracture on both sides, significantly diminished the
      load causing plastic deformation of the plate. If bone contact was not present at
      the fracture site due to comminution, a greater working length also led to
      earlier failure in dynamic loading tests. For simple fractures with a small
      fracture gap and bone contact under dynamic load, the number of cycles until
      failure was greater than one million for all tested constructs. Plate failures
      invariably occurred through the DCP hole where the highest von Mises stresses
      were found in the finite element analysis (FEA). This stress was reduced in
      constructions with bone contact by increasing the bridging length. On the other
      hand, additional screws increased the implant stress since higher loads were
      needed to achieve bone contact. Based on the present results, the following
      clinical recommendations can be made for the locked internal fixator in bridging
      technique as part of a minimally invasive percutaneous osteosynthesis (MIPO): for
      fractures of the lower extremity, two or three screws on either side of the
      fracture should be sufficient. For fractures of the humerus or forearm, three to
      four screws on either side should be used as rotational forces predominate in
      these bones. In simple fractures with a small interfragmentary gap, one or two
      holes should be omitted on each side of the fracture to initiate spontaneous
      fracture healing, including the generation of callus formations. In fractures
      with a large fracture gap such as comminuted fractures, we advise placement of
      the innermost screws as close as practicable to the fracture. Furthermore, the
      distance between the plate and the bone ought to be kept small and long plates
      should be used to provide sufficient axial stiffness.

PMID- 14580983
TI  - The LCP-concept in the operative treatment of distal humerus fractures-
      biological, biomechanical and surgical aspects.
AB  - Distal humerus fractures in adults are treated by open reduction and internal
      fixation, which produces good results in the majority of patients. However, in
      elderly patients or in cases with metaphyseal comminution, stable fracture
      fixation still remains problematic. Anatomical joint reconstruction and primary
      stable osteosynthesis are often particularly difficult to achieve in this group
      of patients since poor bone mineral quality is frequently encountered.
      Consequently, longer immobilization is necessary, which is known to negatively
      influence functional outcome. Over the past few years, double-plate
      osteosynthesis techniques using different configurations have become the
      treatment of choice. Nevertheless, complications due to inappropriate primary
      stability and/or implant failure have been described. Investigations on whether
      the recently introduced Locking Compression Plates (LCPs) could enhance primary
      stability are rare. On the basis of clinical and biomechanical experiences, the
      authors consider LCPs a helpful tool for increasing primary stability in
      osteosynthesis of distal humerus fractures. LCPs might be of substantial
      advantage in patients with diminished bone mineral quality or in the presence of
      metaphyseal comminution.

PMID- 14580984
TI  - General principles for the clinical use of the LCP.
AB  - The basic principles of an internal fixation procedure using a conventional plate
      and screw system (compression method) are direct, anatomical reduction and stable
      internal fixation of the fracture. Wide exposure of the bone is usually necessary
      to gain access to and provide good visibility of the fracture zone to allow
      reduction and plate fixation to be performed. This procedure requires pre
      contouring of the plate to match the anatomy of the bone. The screws are
      tightened to fix the plate onto the bone, which then compresses the plate onto
      the bone. The actual stability results from the friction between the plate and
      the bone. Anatomical reduction of the fracture was the goal of conventional
      plating technique, but over time a technique for bridging plate osteosynthesis
      has been developed for multifragmentary shaft fractures that, thanks to a
      reduction of vascular damage to the bone, permits healing with callus formation,
      as seen after locked nailing. Since the damage to the soft tissues and the blood
      supply is less extensive, more rapid fracture healing can be achieved. The newly
      developed, so-called locked internal fixators (e.g.PC-Fix and Less Invasive
      Stabilization System (LISS)), consist of plate and screw systems where the screws
      are locked in the plate. This locking minimizes the compressive forces exerted by
      the plate on the bone. This method of screw-plate fixation means that the plate
      does not need to touch the bone at all, which is of particular advantage in so
      called Minimal Invasive Percutaneous Osteosynthesis (MIPO). Precise anatomical
      contouring of a plate is no longer necessary thanks to these new screws and
      because the plate does not need to be pressed on to the bone to achieve
      stability. This prevents primary dislocation of the fracture caused by inexact
      contouring of a plate. The LISS plates are precontoured to match the average
      anatomical form of the relevant site and, therefore, do not have to be further
      adapted intraoperatively. The development of the locked internal fixator method
      has been based on scientific insights into bone biology especially with reference
      to its blood supply. The basic locked internal fixation technique aims at
      flexible elastic fixation to initiate spontaneous healing, including its
      induction of callus formation. This technology supports what is currently known
      as MIPO. The development of the Locking Compression Plate (LCP) has only been
      possible based on the experience gained with the PC-Fix and LISS. With reference
      to the mechanical, biomechanical and clinical results, the new AO LCP with
      combination holes can be used, depending on the fracture situation, as a
      compression plate, a locked internal fixator, or as an internal fixation system
      combining both techniques. The LCP with combination holes can also be used,
      depending on the fracture situation, in either a conventional technique
      (compression principle), bridging technique (internal fixator principle), or a
      combination technique (compression and bridging principles). A combination of
      both screw types offers the possibility to achieve a synergy of both internal
      fixation, methods. If the LCP is applied as a compression plate, the operative
      technique is much the same as conventional technique, in which existing
      instruments and screws can be used. The internal fixator method can be applied
      through an open but less invasive or an MIPO approach. An indirect closed
      reduction is necessary when using the LCP in the internal fixator method bridging
      the fracture zone. A combination of both plating techniques is possible and
      valuable, depending on the indication. It is important to command a knowledge of
      both techniques and their different features.

PMID- 14580985
TI  - First clinical results of the Locking Compression Plate (LCP).
AB  - The Locking Compression Plate (LCP) is a new screw-plate system that offers the
      possibility of inserting conventional and locking head screws into the specially
      designed combination holes. It represents a further development of the PC-Fix and
      the LISS and was released for clinical application in March 2000. In a
      prospective multicentre study, the new system was used to treat 144 patients (f:
      67, m: 77; average age: 51.4 years) with 169 fractures: of these, 57 were tibial
      fractures, 45 humerus, 19 radius and 18 femoral. After one year, clinical and
      radiological follow-up assessment was carried out on 127 patients with 151
      fractures (88%). In 130 fractures (86%), healing took place within the expected
      period and without complication or secondary dislocation ("uneventful healing").
      In 19 patients, a total of 27 unexpected complications occurred ("adverse
      events"), in which 18 revision operations were necessary in 13 patients: five for
      implant loosening/pull-out, four for plate failure, one for non-union, five for
      secondary fractures immediately adjacent to the implant after a subsequent injury
      and two for infection. Analysis by a committee of experts indicated that
      mechanical complications arose entirely from technical errors of application
      (incorrect fixation technique, incorrect choice of plate). No purely implant
      related complications were observed. The new system can be regarded as
      technically mature. It offers numerous fixation possibilities and has proven its
      worth in complex fractures situations and in revision operations after the
      failure of other implants. A good knowledge of biomechanics is essential as well
      as precise preoperative planning.

PMID- 14580986
TI  - TomoFix: a new LCP-concept for open wedge osteotomy of the medial proximal tibia-
      early results in 92 cases.
AB  - High Tibial Osteotomy (HTO) is an established treatment for unicompartmental
      osteoarthritis of the knee with malalignment. The classic procedure for
      correcting varus deformity is the lateral closed wedge osteotomy of the tibia
      with osteotomy of the fibula. The disadvantages of this technique are well known.
      Open wedge osteotomy from the medial side eliminates the risk of compartment
      syndrome and peroneal nerve injuries. A new fixation device (TomoFix) with an
      adapted surgical technique allows stable fixation of the osteotomy without the
      need to fill the osteotomy gap with bone grafts. In a prospective study, 92
      consecutive cases were treated with this procedure. Bony healing with remodelling
      of the medial and posterior cortical bone was observed. Full weight-bearing was
      possible ten weeks after surgery. There were no implant failures. Complications
      included one delayed union, two revarisations and one deep infection.

PMID- 14580987
TI  - Guidelines for the clinical application of the LCP.
AB  - The Locking Compression Plate (LCP), in combination with the LISS and the PHILOS,
      is part of a new plate generation requiring an adapted surgical technique and new
      thinking about commonly used concepts of internal fixation using plates. The
      following guidelines are needed to avoid failures and possible complications in
      the hands of surgeons not yet confident with the new implant philosophy. The
      importance of the reduction technique and minimal-invasive plate insertion and
      fixation is addressed to keep bone viability undisturbed. Understanding of
      mechanical background for choosing the proper implant length and the type and
      number of screws is essential to obtain a sound fixation with a high plate span
      ratio and a low plate screw density. A high plate span ration decreases the load
      onto the plate. A high working length of the plate in turn reduces the screw
      loading, thus fewer screws need to be inserted and the plate screw density can be
      kept low. Knowledge of the working length of the screw is helpful for the proper
      choice of monocortical or bicortical screws. Selection is done according to the
      quality of the bone structure and is important to avoid problems at the screw
      thread bone interface with potential pullout of screws and secondary
      displacement. Conclusive rules are given at the end of this chapter.

PMID- 14580991
TI  - The unusual high molecular mass of Bothrops protease A, a trypsin-like serine
      peptidase from the venom of Bothrops jararaca, is due to its high carbohydrate
      content.
AB  - Bothrops protease A (BPA) is a serine peptidase isolated from the venom of
      Bothrops jararaca. Unlike many venom enzymes, it is stable at pHs between 3 and 9
      and resists heating at 86 degrees C for 10 min. Mature snake venom serine
      peptidases of the chymotrypsin family are in general glycoproteins composed of
      around 232 amino acids and their molecular masses vary between 25 and 40 kDa. BPA
      is a glycosylated protein that migrates on SDS-polyacrylamide gel electrophoresis
      (PAGE) as a single band of 67 kDa. In order to find out whether BPA has the
      typical serine peptidase primary structure or if it is composed of a longer amino
      acid sequence, we cloned a cDNA encoding BPA. Its deduced amino acid sequence
      showed that BPA is composed of 234 residues with a calculated molecular mass of
      25,409 Da implying that approximately 62% of its molecular mass assessed by SDS
      PAGE is due to carbohydrate moieties. Eight putative N-glycosylation and two
      putative O-glycosylation sites were found in BPA amino acid sequence.
      Deglycosylation experiments indicated that all 10 potential glycosylation sites
      in BPA are utilized. Complete N- and O-deglycosylation was only achieved under
      denaturing conditions and generated main products of 25 and 55 kDa, respectively,
      which were enzymatically inactive. N-deglycosylation under non-denaturing
      conditions was only partial and gave a main product of 50 kDa and fragments
      ranging from 25 to approximately 10 kDa. Kinetic parameters K(m) and V(max) of
      partially N-deglycosylated BPA upon substrate Bz-Arg-pNA were similar to the
      native form. However, when partially N-deglycosylated BPA was submitted to pH 3
      and pH 10, it appeared to be unstable as it underwent hydrolysis, as shown by the
      presence of two main products of 30 and 12 kDa while the 50 kDa protein band
      disappeared. These changes also had effects on V(max) upon Bz-Arg-pNA which
      dropped to approximately 45%, while K(m) values remained unchanged. Fluorescence
      emission spectroscopy indicated that in partially N-deglycosylated BPA,
      tryptophan residues are more exposed to a polar environment than in the fully
      glycosylated protein. Taken together, these studies indicate that glycosylation
      has a stabilizing effect on BPA.

PMID- 14580992
TI  - Effects of arginine on rabbit muscle creatine kinase and salt-induced molten
      globule-like state.
AB  - The arginine (Arg)-induced unfolding and the salt-induced folding of creatine
      kinase (CK) have been studied by measuring enzyme activity, fluorescence emission
      spectra, native polyacrylamide gel electrophoresis and size exclusion
      chromatography (SEC). The results showed that Arg caused inactivation and
      unfolding of CK, but there was no aggregation during CK denaturation. The
      kinetics of CK unfolding followed a one-phase process. At higher concentrations
      of Arg (>160 mM), the CK dimers were fully dissociated, the alkali characteristic
      of Arg mainly led to the dissociation of dimers, but not denaturation effect of
      Arg's guanidine groups on CK. The inactivation of CK occurred before noticeable
      conformational changes of the whole molecules. KCl induced monomeric and dimeric
      molten globule-like states of CK denatured by Arg. These results suggest that as
      a protein denaturant, the effect of Arg on CK differed from that of guanidine and
      alkali, its denaturation for protein contains the double effects, which acts not
      only as guanidine hydrochloride but also as alkali. The active sites of CK have
      more flexibility than the whole enzyme conformation. Monomeric and dimeric molten
      globule-like states of CK were formed by the salt inducing in 160 and 500 mM Arg
      H(2)O solutions, respectively. The molten globule-like states indicate that
      monomeric and dimeric intermediates exist during CK folding. Furthermore, these
      results also proved the orderly folding model of CK.

PMID- 14580993
TI  - Fluorometric studies of ligand-induced conformational changes of CD38.
AB  - The lymphoid surface antigen CD38 is a NAD(+)-glycohydrolase that also catalyzes
      the transformation of NAD(+) into cyclic ADP-ribose, a calcium mobilizing second
      messenger. In addition, ligation of CD38 by antibodies triggers signaling in
      lymphoid cells. Since the cytoplasmic tail of CD38 is dispensable for this latter
      property, we have previously proposed that CD38-mediated receptor signal
      transduction might be regulated by its conformational state. We have now examined
      the molecular changes of this protein during its interaction with NAD(+) by
      measuring the intrinsic fluorescence of CD38. We have shown that addition of the
      substrate produced a dramatic decrease in the fluorescence of the catalytically
      active recombinant soluble ectodomain of murine CD38. Analysis of this event
      revealed that the catalytic cycle involves a state of the enzyme that is
      characterized by a low fluorescence which, upon substrate turnover, reverts to
      the initial high intrinsic fluorescence level. In contrast, non-hydrolyzable
      substrates trap CD38 in its altered low fluorescence state. Studies with the
      hydrophilic quencher potassium iodide revealed that the tryptophan residues that
      are mainly involved in the observed changes in fluorescence, are remote from the
      active site. Similar data were also obtained with human CD38, indicating that
      studies of intrinsic fluorescence will be useful in monitoring the
      transconformation of CD38 from different species. Together, these data
      demonstrate that CD38 undergoes a reversible conformational change after
      substrate binding, and suggest a mechanism by which this change could alter
      interactions with different cell-surface partners.

PMID- 14580994
TI  - Solid/gas biocatalysis: an appropriate tool to study the influence of organic
      components on kinetics of lipase-catalyzed alcoholysis.
AB  - The influence of the addition of an extra component in a gaseous reaction medium,
      on the kinetics of alcoholysis of methyl propionate and n-propanol catalyzed by
      immobilized lipase B from Candida antarctica was studied in a continuous
      solid/gas reactor. In this reactor, the solid phase is composed of a packed
      enzymatic sample, which is percolated by gaseous nitrogen, simultaneously
      carrying gaseous substrates and additional components to the enzyme while
      removing reaction products. The system permits to set thermodynamic activity of
      all gaseous components (substrates or not) independently at the desired values.
      This allows in particular to study the influence of an extra added component at a
      constant thermodynamic activity value, contrary to classical solid/liquid system,
      which involves large variations of thermodynamic activity of added solvent, when
      performing full kinetic studies. Alcohol inhibition constant (K(I)) and methyl
      propionate and propanol dissociation constants (K(MP) and K(P)) have been
      determined in the solid/gas reactor in the presence of 2-methyl-2-butanol, and
      compared with values previously obtained in the absence of added component and in
      the presence of water. Complementary experiments were carried out in the presence
      of an apolar compound (hexane) and led to the conclusion that the effect of added
      organic component on lipase-catalyzed alcoholysis is related to their competitive
      inhibitory character towards first substrate methyl propionate. The comparison of
      data obtained in liquid or with gaseous 2-methyl-2-butanol shows that lower K(MP)
      and K(I) are found in gaseous medium, which would correspond on the one hand to a
      lower acylation rate k(2), and on the other hand to a higher binding rate k(1)
      between substrate and free enzyme in gaseous medium.

PMID- 14580995
TI  - Computational modelling of the open-state Kv 1.5 ion channel block by
      bupivacaine.
AB  - Binding of R(+)-bupivacaine to open-state homology models of the mammalian
      K(v)1.5 membrane ion channel is studied using automated docking and molecular
      dynamics (MD) methods. Homology models of K(v)1.5 are built using the 3D
      structures of the KcsA and MthK channels as a template. The packing of
      transmembrane (TM) alpha-helices in the KcsA structure corresponds to a closed
      channel state. Opening of the channel may be reached by a conformational
      transition yielding a bent structure of the internal S6 helices. Our first model
      of the K(v) open state involves a PVP-type of bending hinge in the internal
      helices, while the second model corresponds to a Gly-type of bending hinge as
      found in the MthK channel. Ligand binding to these models is probed using the
      common local anaesthetic bupivacaine, where blocker binding from the
      intracellular side of the channel is considered. Conformational properties and
      partial atomic charges of bupivacaine are determined from quantum mechanical HF/6
      31G* calculations with inclusion of solvent effects. The automated docking and MD
      calculations for the PVP-bend model predict that bupivacaine could bind either in
      the central cavity or in the PVP region of the channel pore. Linear interaction
      energy (LIE) estimates of the binding free energies for bupivacaine predict
      strongest binding to the PVP region. Surprisingly, no binding is predicted for
      the Gly-bend model. These results are discussed in light of electrophysiological
      data which show that the K(v)1.5 channel is unable to close when bupivacaine is
      bound.

PMID- 14580996
TI  - A proposed mechanism for the thermal denaturation of a recombinant Bacillus
      halmapalus alpha-amylase--the effect of calcium ions.
AB  - The thermal stability of a recombinant alpha-amylase from Bacillus halmapalus
      alpha-amylase (BHA) has been investigated using circular dichroism spectroscopy
      (CD) and differential scanning calorimetry (DSC). This alpha-amylase is
      homologous to other Bacillus alpha-amylases where crystallographic studies have
      identified the existence of three calcium binding sites in the structure.
      Denaturation of BHA is irreversible with a T(m) of approximately 89 degrees C and
      DSC thermograms can be described using a one-step irreversible model. A 5 degrees
      C increase in T(m) in the presence of 10-fold excess CaCl(2) was observed.
      However, a concomitant increase in the tendency to aggregate was also observed.
      The presence of 30-40-fold excess calcium chelator (ethylenediaminetetraacetic
      acid (EDTA) or ethylene glycol-bis[beta-aminoethyl ether] N,N,N',N'-tetraacetic
      acid (EGTA)) results in a large destabilization of BHA, corresponding to about 40
      degrees C lower T(m) as determined by both CD and DSC. Ten-fold excess EGTA
      reveals complex DSC thermograms corresponding to both reversible and irreversible
      transitions, which probably originate from different populations of BHA/calcium
      complexes. Combined interpretation of these observations and structural
      information on homologous alpha-amylases forms the basis for a suggested
      mechanism underlying the inactivation mechanism of BHA. The mechanism includes
      irreversible thermal denaturation of different BHA/calcium complexes and the
      calcium binding equilibria. Furthermore, the model accounts for a temperature
      induced reversible structural change associated with calcium binding.

PMID- 14580997
TI  - Localization of ligand-binding sites on human C1q globular head region using
      recombinant globular head fragments and single-chain antibodies.
AB  - As a charge pattern recognition molecule, human C1q can bind a range of
      immunoglobulin and non-immunoglobulin ligands via its carboxy-terminal globular
      domain and activate the classical complement pathway. Each globular domain has a
      heterotrimeric organization, composed of the carboxy-terminal halves of one A
      (ghA), one B (ghB), and one C (ghC) chain. Recently, we have found that the
      recombinant forms of individual ghA, ghB and ghC bind differentially to IgG, IgM,
      gp41 peptide 601-613 of human immunodeficiency virus-1 (HIV-1), gp21 peptide 400
      429 of human T cell lymphotrophic virus-I (HTLV-I), beta-amyloid peptide, and
      apoptotic cells, suggesting a modular organization of the globular domain. This
      paper examines the interaction of ghA, ghB and ghC with two known C1q ligands:
      Klebsiella pneumoniae porin OmpK36 and salivary agglutinin. In addition, we have
      used a panel of recombinant single-chain antibodies (scFv) specific for ghA, ghB
      and ghC in order to map sites on the heterotrimeric globular domain which are
      likely to interact with IgG1, IgG3, IgM, OmpK36, salivary agglutinin and gp41
      loop peptide. The combined use of recombinant ghA, ghB, ghC and single-chain
      antibodies has revealed at least three ligand-binding sites on the globular
      domain of C1q: one is IgG- and OmpK36-specific, the second (IgM-binding site) is
      most likely overlapping with IgG/OmpK36 binding site, and the third (the gp41
      binding site) seems to be located at the junction between the collagen and
      globular domains.

PMID- 14580998
TI  - Characterization of native and histidine-tagged deoxyxylulose 5-phosphate
      reductoisomerase from the cyanobacterium Synechocystis sp. PCC6803.
AB  - The dxr gene encoding the 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR)
      from the cyanobacterium Synechocystis sp. PCC6803 was expressed in Escherichia
      coli to produce both the native and N-terminal histidine-tagged forms of DXR. The
      enzymes were purified from the cell extracts using either anion exchange
      chromatography or metal affinity chromatography and gel filtration. The purified
      recombinant native and histidine-tagged enzymes each displayed a single band on
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) gels,
      corresponding to the calculated subunit molecular weights of 42,500 and 46,700,
      respectively. By native PAGE, both enzymes were dimers under reducing conditions.
      The kinetic properties for the enzymes were characterized and only minor
      variations were observed, demonstrating that the N-terminal histidine tag does
      not greatly affect the activity of the enzyme. Both enzymes had similar
      properties to previously characterized reductoisomerases from other sources. The
      K(m)'s for the metal ions Mn(2+), Mg(2+), and Co(2+) were determined for native
      DXR for the first time, with the K(m) for Mg(2+) being approximately 200-fold
      higher than the K(m)'s for Mn(2+) and Co(2+).

PMID- 14580999
TI  - IL-2 loaded dextran microspheres with attractive histocompatibility properties
      for local IL-2 cancer therapy.
AB  - Biodegradable dextran microspheres (MS) were developed as a slow-release system
      for interleukin-2 (IL-2) to apply them for local IL-2 therapy of cancer. We
      describe the tissue reactions induced by these MS without or with IL-2 in rats.
      Dextran MS stain bright red-purple with the periodic acid Schiff (PAS),
      visualising the exact spot of IL-2 release and its relation to the histological
      reaction pattern. Subcutaneously injected MS always form a well-circumscribed
      deposit. In the first 2 days there is a PMN inflammation within the MS-deposit,
      but the surroundings show only a scanty inflammatory reaction. The PMN reaction
      is replaced by an abundant macrophage reaction in particular in the MS-deposit.
      At day 21 a fibrous capsule of about 50 mum surrounds the deposit. The effect of
      IL-2 administered in its free form is mainly vascular, with vascular dilatation,
      vascular leakage and oedema. It is remarkable that lymphocytes are present in the
      injection area already at day 2. When IL-2 releasing MS were used, the various
      reactions induced by IL-2 and MS were amplified leading to local necrosis. We
      conclude that neither placebo MS nor IL-2 leads to necrosis after subcutaneous
      injection in rats. In contrast, when IL-2 was released from MS, then massive
      necrosis was induced. This might be due to increased phagocytosis or changes in
      the micro-niche due to the release of humoral factors by the infiltrating cells.
      This is probably fortuitous for local IL-2 therapy of cancer, as massive necrosis
      of tumour cells can be expected to lead to an increased antitumour reaction.

PMID- 14581000
TI  - Effect of MG132, a proteasome inhibitor, on the expression of growth related
      oncogene protein-alpha in human umbilical vein endothelial cells.
AB  - Growth related oncogene protein-alpha (GRO-alpha) is a member of C-X-C chemokine
      and plays an important role in inflammatory responses. Expression of GRO gene
      family is regulated by a number of factors at both transcriptional and
      posttranscriptional levels. In the present study, we have addressed the possible
      regulation of GRO-alpha expression by ubiquitin-proteasome system. Cultures of
      human umbilical vein endothelial cells were treated with a proteasome inhibitor,
      MG132, and the levels of GRO-alpha mRNA were analyzed by reverse transcription
      polymerase chain reaction or northern blotting. Levels of GRO-alpha protein in
      the cell-conditioned medium were determined by enzyme-linked immunosorbent assay.
      MG132 alone increased the levels of GRO-alpha mRNA and protein; however, it did
      not affect the GRO-alpha mRNA induced by lipopolysaccharide (LPS) and inhibited
      the LPS-induced decrease in IkappaB levels. Other proteasome inhibitors, MG115
      and lactacystin, also induced the expression of GRO-alpha mRNA. MG132 induced the
      phosphorylation of p38 MAPK, MEK and JNK. Pretreatment of the cells with
      SB203580, an inhibitor of p38 MAPK, suppressed the MG132-induced GRO-alpha
      expression, but pretreatment of the cells with U0126, PD98059 or SP600125,
      inhibitors of MEK1/2 or JNK, did not influence the effect of MG132. We conclude
      that MG132 upregulates GRO-alpha expression in vascular endothelial cells, at
      least in part, through the activation of p38 MAPK.

PMID- 14581001
TI  - Tumor necrosis factors in a murine model of allergic peritonitis: effects on
      eosinophil accumulation and inflammatory mediators' release.
AB  - In allergic disorders, the role of tumor necrosis factors (TNF) is not well
      established. We investigated the role of TNF in allergic peritonitis induced by
      ovalbumin (OVA) challenge in double TNF (TNF-alpha(-/-)/lymphotoxin-alpha(-/-))
      knock out (TNF-KO) mice. In the peritoneal lavage of TNF-KO mice, mast cell
      number and histamine level (radioenzymatic assay) were similar to that in wild
      type (WT) mice. TNF-alpha (ELISA) and histamine were increased 1 h after
      challenge in WT mice. However, three days later eosinophil number and eosinophil
      peroxidase (EPO) levels (colorimetric-enzymatic assay) were found to be lower in
      TNF-KO mice. A second challenge three days after the first, increased EPO,
      histamine and IL-6 (ELISA) but did not alter eosinophil and mast cell numbers in
      both types of mice. On the other hand histamine and IL-6 were higher, while EPO
      was lower in TNF-KO mice. In conclusion, our findings show that TNF is involved
      in eosinophil accumulation and inflammatory mediators' release in a murine model
      of allergy.

PMID- 14581002
TI  - IFN-alpha and IL-12 activate IFN regulatory factor 1 (IRF-1), IRF-4, and IRF-8
      gene expression in human NK and T cells.
AB  - IFN-alpha and IL-12 are macrophage-derived cytokines that enhance innate and Th1
      immune responses. However, there is little information regarding IFN-alpha and IL
      12 target genes that would be involved in mediating the immunostimulatory effects
      of these cytokines. The interferon regulatory factor (IRF) family of
      transcription factors is known to be involved in controlling lymphocyte
      differentiation and functions. In this work we have studied the effect of IFN
      alpha and IL-12 on the expression of IRF transcription factors in human NK and T
      cells. Both IFN-alpha and IL-12 strongly up-regulated IRF-1, IRF-4, and IRF-8
      mRNA and protein expression. The binding of IRF-4 and IRF-8 to the lambdaB gene
      enhancer sequence was also increased following IFN-alpha- and IL-12-treatment of
      NK and T cells. A GAS element from the promoter region of the IRF-4 gene was
      identified. Following stimulation of cells with IFN-alpha or IL-12, Stat4 was
      found to bind to this IRF-4 GAS element, as detected by EMSA and DNA affinity
      binding, implying that the IRF-4 gene is directly activated by both cytokines.
      Our results suggest that IFN-alpha and IL-12 may enhance innate and Th1 immune
      responses by inducing IRF-1, IRF-4, and IRF-8 gene expression.

PMID- 14581003
TI  - ELR+ CXC chemokines in human milk.
AB  - CXC chemokines bearing the glutamic acid-leucine-arginine (ELR) motif are crucial
      mediators in neutrophil-dependent acute inflammation. Interestingly, however,
      Interleukin (IL)-8/CXC ligand (CXCL) 8 is expressed in human milk in biologically
      significant concentrations, and may play a local maturational role in the
      developing human intestine. In this chemokine subfamily, there are six other
      known peptides beside IL-8/CXCL8, all sharing similar effects on neutrophil
      chemotaxis and angiogenesis. In this study, we measured the concentrations of
      these chemokines in human milk, sought their presence in human mammary tissue by
      immunohistochemistry, and confirmed chemokine expression in cultured human
      mammary epithelial cells (HMECs). Each of the seven ELR(+) CXC chemokines was
      measurable in milk, and except for NAP-2/CXCL7, these concentrations were higher
      than serum. The concentrations were higher in colostrum (except for GRO
      beta/CXCL2 and NAP-2/CXCL7), and correlated negatively with time elapsed
      postpartum. IL-8/CXCL8, GRO-gamma/CXCL3, and ENA-78/CXCL5 concentrations were
      higher in preterm milk. There was intense immunoreactivity in mammary epithelial
      cells for all ELR(+) CXC chemokines, and the intensity of staining was higher in
      breast tissue with lactational changes. The supernatants from confluent HMEC
      cultures also contained measurable concentrations of all the seven ELR(+) CXC
      chemokines. These results confirm that all ELR(+) CXC chemokines are actively
      secreted by the mammary epithelial cells into human milk. Further studies are
      needed to determine if these chemokines share with IL-8/CXCL8 the protective
      effects on intestinal epithelial cells.

PMID- 14581004
TI  - IL-12 reduces the severity of Sendai virus-induced bronchiolar inflammation and
      remodeling.
AB  - The goal of this research was to determine whether differential pulmonary IL-12
      gene expression controls susceptibility to Sendai virus-induced chronic airway
      inflammation and fibrosis in inbred rat strains. Sendai virus-resistant F344 rats
      and susceptible BN rats were studied from 1 to 14 days following virus
      inoculation. F344 rats had 3.4-fold higher IL-12 mRNA levels detected by real
      time PCR in lung than BN rats as early as two days following inoculation. This
      increase in mRNA was associated at two days with increased total IL-12 protein
      and with a 2-fold increase in numbers of bronchiolar, OX-6-positive dendritic
      cells and an increased number of IL-12 p40-positive, bronchiolar macrophages and
      dendritic cells (p<0.05). Virus-susceptible BN rats treated with 3 mug of
      recombinant, mouse IL-12 intraperitoneally at the time of virus inoculation had a
      22.1% decrease in severity of chronic bronchiolar inflammation and a 23.8%
      decrease in fibrosis compared to virus-inoculated BN rats treated with saline. IL
      12 treatment induced increased IFN-gamma mRNA and protein expression after virus
      inoculation (p<0.05). The results demonstrate that there is differential
      pulmonary IL-12 gene expression between virus-susceptible and resistant rat
      strains and that IL-12 treatment can provide significant protection from virus
      induced chronic airway inflammation and remodeling during early life.

PMID- 14581005
TI  - Imaging in severe acute respiratory syndrome (SARS).
AB  - Severe acute respiratory syndrome (SARS) is a highly infectious disease caused by
      a novel coronavirus, and has become pandemic within a short period of time.
      Imaging plays an important role in the diagnosis, management and follow-up of
      patients with SARS. The current status of imaging in SARS is presented in this
      review.

PMID- 14581006
TI  - MRI of neonatal encephalopathy.
AB  - We present the magnetic resonance imaging (MRI) findings in neonatal
      encephalopathy, including hypoxic-ischaemic encephalopathy, perinatal/neonatal
      stroke, metabolic encephalopathy from inborn errors of metabolism, congenital
      central nervous system infections and birth trauma. The applications of advanced
      MRI techniques, such as diffusion-weighted imaging and magnetic resonance
      spectroscopy are emphasized.

PMID- 14581007
TI  - Imaging of intra-articular osteoid osteoma.
AB  - Intra-articular osteoid osteoma accounts for approximately 13% of all osteoid
      osteomas and presents as a monoarthropathy. Radiographs commonly do not identify
      the nidus, and in this event, MRI is likely to be the next imaging investigation.
      MRI may show a variety of appearances depending upon the age of the lesion. This
      article illustrates the imaging features of intra-articular osteoid osteoma, with
      emphasis on MRI. CT remains the investigation of choice for identifying the
      nidus.

PMID- 14581008
TI  - Thoracic radiology--questions, questions, questions.

PMID- 14581009
TI  - Use of multidetector-row CT colonography for detection of colorectal neoplasia in
      patients referred via the Department of Health "2-Week-wait" initiative.
AB  - AIM: Patients referred under the Department of Health 2-week wait initiative with
      symptoms of colorectal cancer frequently undergo whole-colon examination. We
      investigated the use of computed tomography (CT) colonography as an alternative
      to colonoscopy in this scenario. MATERIALS AND METHODS: Fifty-four consecutive
      patients, referred via the 2-week wait initiative and scheduled for colonoscopy,
      consented to undergo multidetector CT colonography immediately before endoscopy.
      The site and morphology of any polyp or cancer detected by CT was noted and
      comparison made with subsequent colonoscopy. RESULTS: Colonoscopy detected polyps
      or cancer in 29 patients (53.7%). CT colonography prospectively detected 18 of 41
      (44%) polyps of 1-5 mm, three of four (75%) polyps of 6-9 mm, four of four (100%)
      polyps 10 mm or larger, and five of six (83%) cancers. The missed cancer occurred
      early in the series and was a perceptive error. The overall sensitivity,
      specificity, positive predictive value and negative predictive value of CT
      colonography for cancer and polyps 10 mm or greater on a per patient basis were
      90, 100, 100 and 98%, respectively. CT detected one renal cancer and one colonic
      cancer, initially missed due to incomplete colonoscopy. CONCLUSION: CT
      colonography is a robust technique for investigation of symptomatic patients. The
      learning curve must be overcome for optimal performance.

PMID- 14581010
TI  - ECG-gated multislice spiral CT for diagnosis of acute pulmonary embolism.
AB  - AIM: The purpose of this study was to determine the feasibility of echocardiogram
      (ECG)-gated multi-slice CT angiography (MCTA) in patients with clinical suspicion
      of acute venous thromboembolism (VTE), to investigate the effect of ECG-gating on
      cardiac motion artefacts, and to determine the diagnostic reader agreement of ECG
      gated MCTA in comparison with conventional MCTA. MATERIALS AND METHODS: Forty
      eight consecutive patients were prospectively enrolled and randomly underwent ECG
      gated (n=25, group 1) or non-ECG-gated (n=23, group 2) eight-slice pulmonary
      MCTA. Image data were evaluated by three independent chest radiologists with
      respect to the presence or absence of emboli at different arterial levels (main,
      lobar, segmental, and subsegmental arteries), and with regard to cardiac motion
      artefacts. Statistical tests used to calculate inter-observer agreement were
      weighted kappa statistics, extended kappa statistics and confidence indices
      indicating three-reader agreement accuracy. RESULTS: Twenty-seven patients
      (56.3%) were diagnosed to have pulmonary embolism (13 from group 1, 14 from group
      2). Cardiac motion artefacts were significantly more frequent in group 2 (70% in
      group 2 versus 13% in group 1, p=0.0001). The overall diagnostic agreement was
      excellent with both MCTA techniques (three-reader confidence index for all
      vascular territories: 0.76 and 0.84 for groups 1 and 2, respectively (extended
      kappa=0.69 and 0.78, respectively); three-reader confidence index for diagnosis
      of VTE: 0.94 and 0.85 for groups 1 and 2, respectively (extended kappa=0.91 and
      0.73, respectively), weighted kappa=0.81-0.83 and 0.92-0.95 for groups 1 and 2,
      respectively, and did not differ significantly between the two groups. In
      addition there was no significant difference of inter-observer agreement in
      either group at any assessed pulmonary arterial level. CONCLUSION: ECG-gated
      pulmonary MCTA is feasible in patients with clinical suspicion of VTE. However,
      ECG-gated image acquisition did not influence the diagnostic reader agreement
      accuracy and inter-observer agreement of MCTA. Hence, it does not appear to be
      advantageous for the MCTA diagnosis of pulmonary embolism.

PMID- 14581011
TI  - Accuracy of high-resolution sonography compared with magnetic resonance imaging
      in the diagnosis of head and neck venous vascular malformations.
AB  - AIMS: To evaluate whether modern ultrasound examination helps to establish the
      diagnosis of head and neck venous vascular malformations (VVMs) and whether it
      can delineate their full extent. MATERIALS AND METHODS: Sonographic appearances
      of 30 head and neck VVMs were assessed for: location, extent, internal
      architecture, presence of flow and phleboliths. These results were compared with
      the magnetic resonance imaging (MRI) of the same patients. RESULTS: The lesions
      showed well-defined margins (22 of 30, 73%), heterogeneous (30 of 30, 100%) and
      hypoechoic echo pattern (27 of 30, 90%), with sinusoidal spaces (28 of 30, 93%)
      and phleboliths (24 of 30, 80%) on grey-scale imaging, and flow signal on Doppler
      (28 of 30, 93%). For delineating the extent, ultrasound was comparable with MRI
      in 53% (16 of 30) and inferior to MRI in 47% (14 of 30). Ultrasound did not
      detect deeper extent, intra-osseous involvement and other clinically occult VVMs.
      CONCLUSION: Ultrasound with high-resolution transducers can confidently suggest
      the diagnosis of head and neck VVMs in up to 90% of cases, and delineate the full
      extent of some superficial lesions. The major disadvantage is its inability to
      evaluate intra-osseous involvement and the entire extent of large, deep-seated
      lesions.

PMID- 14581012
TI  - Treatment of complete obstruction of the nasolacrimal system by temporary
      placement of nasolacrimal polyurethane stents: preliminary results.
AB  - AIM: To assess the efficacy of the temporary placement of polyurethane
      nasolacrimal stents as a treatment for complete post-saccal obstruction of the
      lacrimal apparatus. MATERIALS AND METHODS: Polyurethane nasolacrimal stents were
      inserted under radiological guidance in nine patients with grade IV epiphora due
      to complete obstruction of the lacrimal system, at the junction of the lacrimal
      sac and duct (eight patients) or in the lacrimal duct (one patient). On average,
      the stents were removed 4 months (range: 3-6 months) after insertion.
      Dacryocystography was performed immediately before and after each stent was
      removed. Subsequently, periodic clinical and radiological examinations were
      performed until recurrence of the epiphora, at which point follow-up concluded.
      RESULTS: All patients remained free of epiphora and clinical inflammation while
      the stents were in place, but re-obstruction of the lacrimal system occurred in
      all patients less than 2 months after the stents were removed. Adhesion of three
      stents to the lacrimal tract was observed upon removal. In seven cases the
      dacryocystography results at the end of follow-up revealed changes in the
      configuration of the lacrimal apparatus. CONCLUSION: Based on our preliminary
      experience, temporary placement of polyurethane stents would not appear to be an
      efficacious therapeutic option for treating epiphora caused by post-saccal
      obstruction.

PMID- 14581013
TI  - Skeletal muscle metastasis from transitional cell carcinoma of the urinary
      bladder: clinicoradiological features.
AB  - AIM: To define the clinicoradiological characteristics of skeletal muscle
      metastasis from transitional cell carcinoma of the urinary bladder. MATERIALS AND
      METHODS: A retrospective review of all patients with skeletal muscle metastasis
      was undertaken between January 1999 to December 2001. Patients suspected of
      having a metastasis on radiological examinations, and subsequently proven to have
      metastatic disease on histological examination were included in study. The
      clinical presentation and radiological features of five patients with skeletal
      muscle metastasis from bladder tumours were reviewed from hospital records.
      RESULTS: Twenty-four patients had skeletal muscle metastasis from various
      primaries. Of these five patients had previous or concurrent primary tumours in
      the bladder. Patients were aged between 27-70 years (mean 52 years), and all had
      persistent, localized pain with or without accompanying swelling. The muscles
      involved were psoas in three patients, adductor muscles of thigh in one and
      rectus abdominis in one. Four patients had radical cystectomy with urinary
      diversion (two ileal conduit and two orthotopic sigmoid neobladder). One patient
      presented with bladder tumour and concomitant muscular metastasis. All patients
      underwent helical computed tomography (CT) before confirmation of diagnosis by
      fine-needle aspiration (FNA) or biopsy. The typical appearance of low-density
      enhancing lesions on CT was mistaken for abscess in two patients and failure to
      respond to conservative treatment led to suspicion of metastasis. Diagnosis was
      proven histologically in all patients (FNA in three and biopsy in two). All
      patients had palliative chemotherapy (Mitomycin, Vincristine, Adriamycin and
      Cyclophosphamide). Two patients had local palliative 3500 rad radiotherapy for
      persistent pain. Mean survival was 8 months (range 6-12 months). CONCLUSION:
      Muscular metastasis from urothelial tumours typically presents with persistent
      localized pain with or without swelling. The characteristic low-density, ring
      enhancing lesions on CT in a patient with previous or concomitant urothelial
      tumours should raise the suspicion of metastasis until proven otherwise.
      Prognosis is dismal.

PMID- 14581015
TI  - Spontaneous idiopathic bilateral adrenal haemorrhage in adults.

PMID- 14581014
TI  - Bilateral CT-guided percutaneous cordotomy for cancer pain relief.
AB  - AIM: CT-guided percutaneous cordotomy is a useful procedure for treating
      unilateral cancer pain, however, bilateral cordotomy can be required on some
      occasions. We evaluated the effectiveness and complications of bilateral
      cordotomy. MATERIALS AND METHODS: Two hundred and thirty-four patients who
      suffered from unilateral cancer pain underwent CT-guided percutaneous cordotomy.
      The procedure was repeated in 22 patients, and nine patients had bilateral
      cordotomy. Effectiveness and complications were recorded after each procedure.
      RESULTS: Of nine patents (three women and six men) having bilateral percutaneous
      cordotomy in our study, four patients had mirror pain after the first procedure.
      In the remaining five patients the contralateral pain was due to new pain sites.
      The pain scores before and after the first procedure were 9.3 (range 7-10) and
      1.2 (range 0-3), respectively. After the first procedure complete or satisfactory
      pain relief was achieved in all patients. The duration between the two procedures
      ranged from 7-243 days (mean 59.8 days). The pain scores before and after the
      second procedure were 8.4 (range 5-10) and 1.6 (range 0-4), respectively. After
      the second procedure complete or satisfactory pain relief was reported in all
      patients. There were no complications in four patients. One patient developed
      transient motor deficit after the first procedure. Other complications
      (nausea/vomiting, headache, ipsilateral neck pain, postcordotomy dysesthesia)
      were mild and transient. CONCLUSION: CT-guided percutaneous cordotomy is a useful
      procedure for the treatment of severe unilateral cancer pain syndromes. The
      procedure can be repeated on the other side at least 1 week later. These results
      show that the success on the second side appears to be similar to the first side
      with low complication rate for both procedures.

PMID- 14581016
TI  - Intra-testicular pseudotumour mimicking malignancy: ultrasound appearances.

PMID- 14581017
TI  - Acute biliary obstruction caused by biliary ascaris in pregnancy: MR
      cholangiography findings.

PMID- 14581018
TI  - Multiple intra-hepatic portal vein aneurysms: findings on magnetic resonance
      angiography.

PMID- 14581019
TI  - Re: Can radiographers read screening mammograms?

PMID- 14581022
TI  - Prospective comparison of methods of closure of the coronal flap after
      craniofacial surgery in children.
AB  - The coronal flap in children may be closed with clips or sutures. The results of
      closure with clips in patients treated during 1 year at the paediatric
      craniofacial unit, Liverpool, UK, were audited. Eight of 43 required a further
      general anaesthetic for removal of clips. A prospective audit the following year
      of patients whose wounds were closed with a rapidly-absorbed polyglactin suture
      (Vicryl rapide) showed that 3 out of 39 required re-suture of the wound in
      theatre (two following trauma from falls). There was one infection in each group.
      Neither of these patients required formal debridement of the wound in theatre.
      Rapidly-absorbed polyglactin is a safe alternative to clips for wound closure
      after craniofacial surgery in children and the morbidity is less because fewer
      patients have to return to theatre than closure with surgical clips.

PMID- 14581023
TI  - Ultrasound imaging in the preoperative estimation of the size of tracheostomy
      tube required in specialised operations in children.
AB  - BACKGROUND: Some children are dependent on a tracheostomy for many years. As they
      grow, larger tracheostomy tubes may be required. Although tables of sizes of
      tracheas exist for different age groups, they are estimations of normal and may
      not be accurate for atypical cases. Chest radiographs and computed tomograms (CT)
      have been used experimentally to estimate tracheal sizes, but are not in regular
      use. METHOD: High-resolution diagnostic ultrasound imaging was used to estimate
      the internal and external transverse tracheal diameter, and the depth of the
      trachea from the skin surface. This allowed selection of the correct standard
      pattern tracheostomy tube, or the construction of a custom-made tube
      preoperatively. RESULTS: Four children with various abnormalities who were being
      considered for replacement tracheostomies were scanned. In one, diagnostic
      ultrasound confirmed that a new larger fenestrated tube could be placed, which
      subsequently improved vocalisation and respiration. In the other three, the scan
      showed there was no space to allow a larger tube to be placed. The standard
      tables were not suitable for any of these patients. CONCLUSION: High-resolution
      ultrasound has a role in the non-invasive measurement of the size of the tube
      needed for specialised operations in children.

PMID- 14581024
TI  - Psychological consequences of maxillofacial trauma: a preliminary study.
AB  - AIMS: To identify the prevalence of post-traumatic psychological symptoms after
      maxillofacial trauma and prognostic factors related to poor outcome. METHODS:
      Thirty-nine patients were assessed within 10 days of injury and 24 again 4-6
      weeks later using five standardised self-report measures on each occasion and a
      short structured interview at the time of initial contact. RESULTS: Specific post
      traumatic psychological symptoms were present at initial assessment in 21
      patients (54%), with 9 (41%) meeting diagnostic criteria for post-traumatic
      stress disorder at review 4-6 weeks later. Other psychiatric problems, such as
      anxiety and depression, were identified by the General Health Questionnaire and
      the Hospital Anxiety and Depression Scale. Characteristics associated with poorer
      outcome included: a previous history of psychological distress; fear of the
      unknown, and female sex. CONCLUSION: These findings highlight the adverse
      psychological effect of maxillofacial trauma both immediately after the event and
      4-6 weeks after injury. Proper assessment of injured patients must include
      psychological aspects and further research is needed to identify the most
      appropriate response.

PMID- 14581025
TI  - Effects of a single arthrocentesis and a COX-2 inhibitor on disorders of
      temporomandibular joints. A preliminary clinical study.
AB  - Our aim was to examine the short-term effect of combined treatment with single
      arthrocentesis and a COX-2 inhibitor on 26 patients with severe symptoms of
      temporomandibular joint (TMJ) disorders. The severity of the disorders was graded
      according to the degree of restriction of mouth opening and pain score on a
      visual analogue scale. Synovial fluid was collected from the superior joint space
      of the affected TMJ, and arthrocentesis was done with isotonic saline, 200ml.
      Subsequently, etodolac, 400mg/day, was given for 2 weeks. At 14 days, patients
      were re-examined and further specimens of synovial fluid were collected. Patients
      generally lost their symptoms and the severity of the disorders improved
      significantly (P<0.01). The concentrations of total protein and albumin in
      synovial fluid decreased with no statistical significance. However, the
      concentration of matrix metalloproteinase-3 and its ratios to total protein and
      albumin did decrease significantly (P<0.05). Our results suggest that a larger
      controlled study is necessary to clarify the contributory effect of
      arthrocentesis and etodolac for patients with severe symptoms of TMJ disorders.

PMID- 14581026
TI  - Osteosarcoma and chondrosarcoma of the maxilla.

PMID- 14581027
TI  - Great auricular causalgia: an unusual complication of excision of the
      submandibular gland.

PMID- 14581028
TI  - Notoplatysma: an aberrant muscle in the parotid region.

PMID- 14581029
TI  - Cephalic tetanus: report of case.

PMID- 14581030
TI  - Endoscopic approach to removal of an ectopic mandibular third molar.

PMID- 14581031
TI  - The use of the laryngeal mask in minor oral surgery.

PMID- 14581032
TI  - Critical ischaemia of the maxilla treated with hyperbaric oxygen.

PMID- 14581033
TI  - High-flow arteriovenous malformation of the mandible: treatment and 7-year follow
      up.

PMID- 14581034
TI  - Intramuscular injection of botulinum toxin as an adjunct to arthrocentesis of the
      temporomandibular joint: preliminary observations.

PMID- 14581035
TI  - The haemostatic poultice: an aid to microvascular anastomosis.

PMID- 14581036
TI  - Reconstruction of the eyebrow using a combination of hair-bearing composite graft
      and microsurgical hair follicle transplant techniques.
AB  - We present a patient whose eyebrow was restored following a road vehicle crash by
      a postauricular composite graft together with microfollicular hair transplants.

PMID- 14581037
TI  - Audiotaping consultations in a head and neck oncology clinic.

PMID- 14581038
TI  - Massive tumour arising from the hard palate after excision of a pleomorphic
      adenoma.

PMID- 14581039
TI  - Temporary intermaxillary fixation and cross infection control.

PMID- 14581040
TI  - Re: Drage NA, et al. Hemangioma of the body of the mandible: a case report. Br J
      Oral Maxillofac Surg 2003; 41: 112-114.

PMID- 14581041
TI  - Re: Brown JS, Jones DC, Summerwill A et al. Vascularised iliac crest with
      internal oblique muscle for immediate reconstruction after maxillectomy. Br J
      Oral Maxillofac Surg 2002; 40: 183-190.

PMID- 14581042
TI  - Re: Opportunity for dissection for trainees.

PMID- 14581046
TI  - Polycyclic aromatic hydrocarbons in the ambient air of suburban and industrial
      regions of central Taiwan.
AB  - The concentrations of gas-phase and particle-bound polycyclic aromatic
      hydrocarbons (PAHs) were measured simultaneously at an industrial area (Taichung
      Industrial Park) and a suburban area (Tunghai University Campus) in Taichung,
      Taiwan. Twenty-four hours samplings for two consecutive days were performed
      between August and December 2002 at both sampling sites. Ambient air particle
      bound PAHs were collected on quartz filters and gas-phase PAHs were collected on
      glass cartridges using a PUF Sampler, respectively. Both types of samples were
      extracted with a DCM/n-hexane mixture (50/50, v/v) for 24 h, then the extracts
      were subjected to gas chromatography-mass spectrometric (GC-MS) analysis. Total
      PAHs concentrations at the Taichung Industrial Park (TIP) sampling site and the
      Tunghai University Campus (THUC) sampling site were found to be 1232.3+/-963.6
      and 609.8+/-356.3 ng/m(3), respectively. Stationary combustion processes were
      mainly responsible for PAHs sources at the TIP sampling site, while traffic
      vehicle exhaust was the largest contributor for PAHs sources at the THUC sampling
      site.

PMID- 14581047
TI  - Comparison of metastable atom bombardment and electron capture negative
      ionization for the analysis of polychloroalkanes.
AB  - A new method for quantifying C10-C13 polychloroalkanes (PCAs or chloroparaffins,
      CPs) in environmental samples using metastable atom bombardment ionization (MAB)
      and high resolution mass spectrometry is presented. Contrary to electron capture
      negative ionization (ECNI), MAB can produce spectra for molecules having a low
      number of chlorine atoms. These molecules are present in commercial PCAs and are
      responsible for a large fraction of the total PCA concentration in water samples
      analysed. Using ECNI or MAB, no molecular ion can be seen in the spectra. ECNI
      spectra contain important peaks corresponding to [M-Cl]- and [M-HCl]-* while the
      base peak in MAB spectra is [M-Cl]+ with no [M-HCl]+* present. The mass range for
      C10-C13 CPs is very large and scanning the masses for all the compounds involved
      would lead to a loss of sensitivity. Two chromatographic analysis are thus
      performed using high resolution selective ion monitoring with only a limited
      number of masses recorded per run. To reduce analysis time, a short capillary
      column is used. Application of this method to the analysis of high-volumes water
      samples (dissolved and particulates portions separately) from the St. Lawrence
      river near Quebec City using MAB is presented. Contribution of molecules with a
      low chlorine content in the samples account for between 10% and 46% to the total
      concentration. Congeners distribution between the different fractions indicates
      that molecules with a low number of carbon atoms are preferentially retained on
      the particulates. Within a carbon number group, there is a slight tendency to
      accumulate molecules with a high number of chlorine atoms in the dissolved
      fraction.

PMID- 14581048
TI  - Mercury in wild mushrooms and underlying soil substrate from Koszalin, North
      central Poland.
AB  - Concentrations of total mercury were determined by cold-vapour atomic absorption
      spectroscopy (CV-AAS) in 221 caps and 221 stalks of 15 species of wild growing
      higher fungi/mushrooms and 221 samples of corresponding soil substrate collected
      in 1997-98 in Manowo County, near the city of Koszalin in North-central Poland.
      Mean mercury concentrations in caps and stalks of the mushroom species examined
      and soils varied between 30+/-31 and 920+/-280, 17+/-11 and 560+/-220, and 10+/-9
      and 170+/-110 ng/g dry matter, respectively. Cap to stalk mercury concentration
      quotients were from 1.0+/-0.4 in poison pax (Paxillus involutus) to 2.8+/-0.7 in
      slippery jack (Suillus luteus). Brown cort (Cortinarius malicorius), fly agaric
      (Amanita muscaria), orange-brown ringless amanita (A. fulva), red-aspen bolete
      (Leccinum rufum) and mutagen milk cap (Lactarius necator) contained the highest
      concentrations of mercury both in caps and stalks, and mean concentrations varied
      between 600+/-750 and 920+/-280 and 370+/-470 and 560+/-220 ng/g dry matter,
      respectively. An estimate of daily intake of mercury from mushroom consumption
      indicated that the flesh of edible species of mushrooms may not pose hazards to
      human health even at a maximum consumption rate of 28 g/day. However, it should
      be noted that mercury intake from other foods will augment the daily intake
      rates. Species such as the sickener (Russula emetica), Geranium-scented russula
      (R. fellea) and poison pax (P. involutus) did not concentrate mercury as
      evidenced from the bioconcentration factors (BCFs: concentrations in
      mushroom/concentration in soil substrate), which were less than 1. Similarly, red
      hot milk cap (L. rufus), rickstone funnel cap (Clitocybe geotropa) and European
      cow bolete (S. bovinus) were observed to be weak accumulators of mercury. Fly
      agaric (A. muscaria) accumulated great concentrations of mercury with BCFs
      reaching 73+/-42 and 38+/-22 in caps and stalks, respectively. Mercury BCFs of
      between 4.0+/-2.3 and 23+/-25 (caps) and 2.6+/-1.9 and 14+/-12 (stalks) were
      noted for the other mushroom species. Relatively great concentrations of mercury
      in fly agaric (A. muscaria) were due to preferential uptake of this element by
      this species.

PMID- 14581049
TI  - A comparative evaluation of accelerated solvent extraction and Polytron
      extraction for quantification of lipids and extractable organochlorine in fish.
AB  - Optimal conditions for extraction methods using an accelerated solvent extractor
      (ASE) and a Polytron homogenizer were established for quantification of (crude)
      lipids and extractable organochlorine (EOCl) in fish. The two methods, an ASE
      consecutive extraction at 55 and 100 degrees C for ground, freeze-dried filets,
      and a Polytron extraction at room temperature with four repetitions for ground,
      wet filets and with two repetitions for wet fish livers were evaluated in terms
      of reproducibility and comparability. With respect to lipid measurement, the two
      methods have comparable reproducibility and the experimental errors are
      relatively small compared to natural variations of fish to fish within a sampling
      site. For EOCl measurement, the relative standard deviation tends to increase
      with decreasing levels of EOCl in specimens. An important factor for the relative
      standard deviation of measurements of analytes present at trace levels in fish
      matrices is sampling error in taking aliquots. Statistical analysis using a
      paired comparison design showed that measurement values (crude lipids or EOCl)
      obtained from these two extraction methods are, in general, not equivalent. There
      is a good correlation between the two methods for lipid measurement; whereas for
      EOCl measurements, high degrees of correlation exist within the exposed fish
      group, but not in the reference group.

PMID- 14581050
TI  - Adsorption-oxidation of hydrogen sulfide on activated carbon fibers: effect of
      the composition and the relative humidity of the gas phase.
AB  - The removal of hydrogen sulfide by oxidation-adsorption on two type carbon
      fibers, Actitex FC1201 and RS1301, was studied. Two kinetic steps where
      identified. During the first step, the degradation appears to be limited by the
      oxidation reaction. In the second kinetic step, the by-products inhibit the
      hydrogen sulfide degradation. This leads to a limitation in the carbon site's
      accessibility and to a lower kinetic. The Langmuir-Hinshelwood model was used to
      correlate the experimental results and to estimate the kinetic (k) and the
      Langmuir adsorption (K) constants. For FC1201 fibers, the kinetic constant (k) is
      five time higher and the adsorption constant is five time lower compared to the
      RS1301 fibers. The role of the humidity was found to be highly beneficial for the
      removal of hydrogen sulfide. Especially in the second kinetic step, where it
      removes the by-product formed and therefore delays the occurrence of this low
      kinetic step. The kinetic constant (k) is strongly influenced by humidity while
      the Langmuir adsorption constant (K) seems independent. The effect of the nature
      of the gas phase on the reaction kinetic was also studied. Under a dry
      atmosphere, we note that the oxidation-reaction occurs even if the gaseous oxygen
      is not present. This oxidation is due to the oxygen surface function of the
      carbon fibers. Moreover, the degradation kinetic is faster under a dry nitrogen
      atmosphere. The presence of water traces leads to the acidification of the carbon
      surface, under oxygen or carbon dioxide atmospheres, and hence limits the
      hydrogen sulfide dissociation. In a humid atmosphere, the oxygen or carbon
      dioxide leads to a faster reaction kinetic. The acidification of the carbon
      surface is largely counterbalanced by the dissolution of the by-products.

PMID- 14581051
TI  - Atrazine distribution measured in soil and leachate following infiltration
      conditions.
AB  - Atrazine transport through packed 10 cm soil columns representative of the 0-10
      cm soil horizon was observed by measuring the atrazine recovery in the total
      leachate volume, and upper and lower soil layers following infiltration of 7.5 cm
      water using a mechanical vacuum extractor (MVE). Measured recoveries were
      analyzed to understand the influence of infiltration rate and delay time on
      atrazine transport and distribution in the column. Four time periods (0.28, 0.8,
      1.8, and 5.5 h) representing very high to moderate infiltration rates (26.8, 9.4,
      4.2, and 1.4 cm/h) were used. Replicate soil columns were tested immediately and
      following a 2-d delay after atrazine application. Results indicate atrazine
      recovery in leachate was independent of infiltration rate, but significantly
      lower for infiltration following a 2-d delay. Atrazine distribution in the 0-1
      and 9-10 cm soil layers was affected by both infiltration rate and delay. These
      results are in contrast with previous field and laboratory studies that suggest
      that atrazine recovery in the leachate increases with increasing infiltration
      rate. It appears that the difference in atrazine recovery measured using the MVE
      and other leaching experiments using intact soil cores from this field site and
      the rain simulation equipment probably illustrates the effect of infiltrating
      water interacting with the atrazine present on the soil surface. This work
      suggests that atrazine mobilization from the soil surface is also dependent on
      interactions of the infiltrating water with the soil surface, in addition to the
      rate of infiltration through the surface soil.

PMID- 14581052
TI  - Kinetic and chemical assessment of the UV/H2O2 treatment of antiepileptic drug
      carbamazepine.
AB  - The UV/H2O2-induced degradation of carbamazepine, a worldwide used antiepileptic
      drug, recently found as contaminant in many municipal sewage treatment plant
      (STP) effluents and other aquatic environments, is investigated. The oxidation
      treatment caused an effective removal of the drug. At complete abatement of the
      substrate after 4 min treatment, a 35% value of removed total organic carbon
      (TOC) was obtained. A kinetic constant of (2.05+/-0.14) x 10(9) lmol(-1)s(-1) was
      determined for OH radical attack to carbamazepine in the UV/H2O2 process.
      Preparative TLC of the reaction mixture led to the isolation of acridine-9
      carboxaldehyde as a reaction intermediate. HPLC and GC/MS analysis indicated
      formation of small amounts of acridine, salicylic acid, catechol and anthranilic
      acid among the reaction products. Under the same reaction conditions,
      synthetically prepared 10,11-epoxycarbamazepine was easily degraded to acridine
      as main product, suggesting that this epoxide is a likely intermediate in the
      oxidative conversion of carbamazepine to acridine. Under sunlight irradiation,
      carbamazepine in water underwent slow degradation to afford likewise acridine as
      main product. In view of the mutagenic properties of acridine, these results
      would raise important issues concerning the possible environmental impact of
      carbamazepine release through domestic wastewaters and support the importance of
      prolonged oxidation treatments to ensure complete degradation of aromatic
      intermediates.

PMID- 14581053
TI  - The effect of pH, ion strength and reactant content on the complexation of Cu2+
      by various natural organic ligands from water and soil in Hong Kong.
AB  - The complexation constants for copper associated with different natural organic
      ligands, including dissolved organic carbon (DOC) extracted from water, water
      soluble organic carbon (WSOC), fulvic acid (FA) and humic acid (HA) from soil,
      were determined and then compared based on discrete single site model. Both ion
      selective electrode (ISE) and anodic stripping voltammetry were used to determine
      the content of free copper ions, while the relative number of complexation sites
      was estimated using a fluorescence quenching (FQ) at the same time. ISE proved to
      be the most applicable technique when the concentration of copper was above 10(
      7) moll(-1). The logk values for two WSOC sample sites (Song Ziyuan and Xin
      Niangtan) were 4.64 and 4.66; higher than both the DOC and HA values yet lower
      than the FA values, which were unusually high due to unavoidable pollution from
      the cation exchange resin used during the purification process. Binding
      affinities between the copper ions and the organic ligands obtained from streams
      in Yong Wei (DOC) and Song Ziyuan (WSOC) were influenced by pH, ion strength, and
      reactant concentration. Values for logk increased with increases in pH (ion
      strength of 0.1 N). At pH 4, the logk values decreased with increases in the
      supporting electrolyte concentration and total copper ion additions.

PMID- 14581054
TI  - Monitoring of reduced sulfur compounds in the atmosphere of Gosan, Jeju Island
      during the Spring of 2001.
AB  - The atmospheric concentrations of dimethylsulfide (DMS) and carbon disulfide
      (CS2) were measured concurrently with relevant environmental parameters at Gosan,
      Jeju Island, Korea during 5-26 April 2001. The mean concentrations for these two
      compounds were 18.7+/-17.9 and 6.4+/-9.9 pptv, respectively. Results of our
      analysis indicated that relative temporal variations between DMS and CS2 can be
      best described by dividing the whole data set into three different periods which
      reflect the variable transport patterns of air masses into the study area.
      (Periods I, II, and III denote: 5-10, 10-18, and 19-26 April.) The environmental
      conditions during those three periods varied greatly. The effects of continental
      and/or oceanic processes were evident for certain periods, yielding diverse
      relationships between DMS and CS2 in both absolute and relative terms. Most
      observed variations were best explained in terms of an interplay between
      source/sink processes and air mass transport patterns. The sea-to-air flux of
      DMS, when estimated using our measurement data during this study period, was
      approximately 4 micromole m(-2)d(-1).

PMID- 14581055
TI  - Thermodynamic properties of several soil- and sediment-derived natural organic
      materials.
AB  - Improved understanding of the structure of soil- and sediment-derived organic
      matter is critical to elucidating the mechanisms that control the reactivity and
      transport of contaminants in the environment. This work focuses on an
      experimental investigation of thermodynamic properties that are a function of the
      macromolecular structure of natural organic matter (NOM). A suite of thermal
      analysis instruments were employed to quantify glass transition temperatures
      (Tg), constant-pressure specific heat capacities (Cp), and thermal expansion
      coefficients (alpha) of several International Humic Substances Society (IHSS)
      soil-, sediment-, and aquatic-derived NOMs. Thermal mechanical analysis (TMA) of
      selected NOMs identified Tgs between 36 and 72 degrees C, and alphas ranging from
      11 mum/m degrees C below the Tg to 242 mum/m degrees C above the Tg. Standard
      differential scanning calorimetry (DSC) and temperature-modulated differential
      scanning calorimetry (TMDSC) measurements provided additional evidence of glass
      transition behavior, including identification of multiple transition behavior in
      two aquatic samples. TMDSC also provided quantitative measures of Cp at 0 and 25
      degrees C, ranging from 1.27 to 1.44 J/g degrees C. Results from TMA, DSC, and
      TMDSC analyses are consistent with glass transition theories for organic
      macromolecules, and the glass transition behavior of other NOM materials reported
      in previous studies. Discussion of the importance of quantifying these
      thermodynamic properties is presented in terms of improved physical and chemical
      characterization of NOM structures, and in terms of providing constraints to
      molecular simulation models of NOM structures.

PMID- 14581056
TI  - A study of the particulate matter PM10 composition in the atmosphere of Chillan,
      Chile.
AB  - Inhalable particulate matter (PM10) concentrations were measured over 24-h
      intervals at six different urban sites in the city of Chillan from September 2001
      to April 2003. Sampling locations were selected to represent central city,
      commercial, residential, and industrial portions of the city. Chemical
      composition of PM10 was performed to samples of 47 mm diameter Teflon membranes
      within the city of Chillan. The spatial and temporal variability of the chemical
      composition of PM10 was evaluated taking into account additional data from
      meteorology and further air pollutants. The majority of PM mass was comprised of
      carbon, nitrate, sulfate, ammonium, and crustal components but in different
      proportion on different days and at different sites. The chemical analyses showed
      that carbonaceous substances and crustal material were the most abundant
      component of PM10 during the winter and summer, respectively. The concentrations
      of PM10 were higher during the cold season than during the warm season. The PM10
      concentrations were higher in the downtown area of the city of Chillan, where
      also the chemical composition was more variable due to urban traffic and other
      anthropogenic sources.

PMID- 14581058
TI  - Solid phase microextraction as a tool to predict internal concentrations of soil
      contaminants in terrestrial organisms after exposure to a laboratory standard
      soil.
AB  - Uptake and accumulation of three chlorobenzenes was studied in both biota
      (Enchytraeus crypticus) and 30 mum polydimethylsiloxane (PDMS) solid phase
      microextraction (SPME) fibers after exposure to spiked OECD soil. The OECD soil
      was spiked with three different concentrations of all contaminants. Uptake of all
      three chlorobenzenes in E. crypticus was fast and steady state levels were
      reached within 2-4 days. Also in the PDMS-SPME fibers uptake was very fast for
      all three compounds, with steady state levels reached after 1 day. Comparison of
      steady state levels in biota and in the PDMS-SPME fibers showed a relationship
      which was consistent over the range of concentrations of chlorobenzenes in soil
      and the difference in logKow. This shows that measuring the concentrations of
      hydrophobic chemicals in a hydrophobic phase such as PDMS can be used as a simple
      tool to estimate internal concentrations of these chemicals in biota exposed to
      complex matrices such as soil.

PMID- 14581059
TI  - Plant uptake of aldicarb from contaminated soil and its enhanced degradation in
      the rhizosphere.
AB  - Experiments were conducted to investigate the degradation of aldicarb, an oxime
      carbamate insecticide, in sterile, non-sterile and plant-grown soils, and the
      capability of different plant species to accumulate the pesticide. The
      degradation of aldicarb in soil followed first-order kinetics. Half lives (t1/2)
      of aldicarb in sterile and non-sterile soil were 12.0 and 2.7 days, respectively,
      which indicated that microorganisms played an important part in the degradation
      of aldicarb in soil. Aldicarb disappeared more quickly (p< or =0.05) in the soil
      with the presence of plants, and t1/2 of the pesticide were 1.6, 1.4 and 1.7 days
      in the soil grown with corn, mung bean and cowpea, respectively. Comparison of
      plant-promoted degradation and plant uptake showed that the enhanced removal of
      aldicarb in plant-grown soil was mainly due to plant-promoted degradation in the
      rhizosphere.

PMID- 14581057
TI  - Biodegradability of wheat gluten based bioplastics.
AB  - A large variety of wheat gluten based bioplastics, which were plasticized with
      glycerol, were subjected to biodegradation. The materials covered the total range
      available for the biochemical control parameter Fi, which expresses the
      percentage of aggregated proteins. This quantity can be related to the density of
      covalent crosslinks in the wheat gluten network, which are induced by
      technological treatments. The biodegradability tests were performed in liquid
      medium (modified Sturm test) and in farmland soil. All gluten materials were
      fully degraded after 36 days in aerobic fermentation and within 50 days in
      farmland soil. No significant differences were observed between the samples. The
      mineralization half-life time of 3.8 days in the modified Sturm test situated
      gluten materials among fast degrading polymers. The tests of microbial inhibition
      experiments revealed no toxic effects of the modified gluten or of its
      metabolites. Thus, the protein bulk of wheat gluten materials is non-toxic and
      fully biodegradable, whatever the technological process applied.

PMID- 14581061
TI  - Quantum vs. topological descriptors in the development of molecular models of
      groundwater pollution by pesticides.
AB  - Using monitoring observations from two, independent studies of US groundwater
      comprising a total of 61 pesticide compounds, this study has shown that those
      compounds found in groundwater can be distinguished from those that cannot be
      found in groundwater on the basis of semi-empirical, quantum chemical and
      empirical molecular descriptors. For the semi-empirical descriptors, logistic
      regression models have been developed and validated against the dataset based on
      the semi-empirical and quantum chemical descriptors. Logistic regression models,
      based on the Debye dipole moment (mu), the hydration energy (DeltaHhyd), and van
      der Waals volume (VvdW), resulted in a maximal explained variation in the data of
      74%. When topological indices were also included the explained variance in data
      increased to 91%, with 86% of the variation being explained by the rule that a
      compound will be found in groundwater if: 0.28mu < 6chip(v) where 6chip(v) is the
      sixth-order molecular path connectivity and mu is the dipole moment of the
      compound. The significance of the dipole moment and hydration energy (or van der
      Waals volume) indicates that it is water solubility that controls mobility, with
      the inclusion of topological descriptors representing structural factors limiting
      the solubility. The dependence of leaching potential on the descriptors that
      control solubility indicates that predictions of environmental fate based on this
      approach may represent a strong alternative to the use of adsorption and
      degradation parameters.

PMID- 14581060
TI  - Development and validation of a method for determination of trace levels of
      alkylphenols and bisphenol A in atmospheric samples.
AB  - A method has been developed and validated in order to assess the occurrence of
      the alkylphenols tert-octylphenol and the isomers of technical nonylphenol as
      well as bisphenol A in gasphase and aerosol samples of a remote area. Gasphase
      samples were adsorbed to XAD2 resin, aerosol samples were taken on glass fiber
      filters. After ultrasonic extraction, clean-up by column chromatography and
      silylation of the analytes, ten nonylphenol peaks were quantified separately
      using a GC-MSD-SIM method. The absolute limits of detection and determination are
      in the range of a few pg per compound, which is a prerequisite for the
      quantification of the analytes in relatively unpolluted air. The precision of the
      whole analytical method is in the range of 1-17% and the recoveries range from
      57% to 80%. Problems were encountered during method development due to the
      tendency of the analytes to sorb to glass surfaces. Silanisation of glassware was
      crucial to achieve acceptable recoveries. The widespread use of the analytes in
      plastic resins resulted in sample contamination. For this reason a careful choice
      of sampling material was necessary. Measured concentrations in gasphase samples
      (lower nanogram per m3 range) and aerosol samples (upper picogram per m3 range)
      are one to three orders of magnitude below already published concentrations.

PMID- 14581062
TI  - Bioanalytical liquid chromatography tandem mass spectrometry methods on
      underivatized silica columns with aqueous/organic mobile phases.
AB  - This review article summarizes the recent progress on bioanalytical LC-MS/MS
      methods using underivatized silica columns and aqueous/organic mobile phases.
      Various types of polar analytes were extracted by using protein precipitation
      (PP), liquid/liquid extraction (LLE) or solid-phase extraction (SPE) and were
      then analyzed using LC-MS/MS on the silica columns. Use of silica columns and
      aqueous/organic mobile phases could significantly enhance LC-MS/MS method
      sensitivity, due to the high organic content in the mobile phase. Thanks to the
      very low backpressure generated from the silica column with low aqueous/high
      organic mobile phases, LC-MS/MS methods at high flow rates are feasible,
      resulting in significant timesaving. Because organic solvents have weaker eluting
      strength than water, direct injection of the organic solvent extracts from the
      reversed-phase solid-phase extraction onto the silica column was possible.
      Gradient elution on the silica columns using aqueous/organic mobile phases was
      also demonstrated. Contrary to what is commonly perceived, the silica column
      demonstrated superior column stability. This technology can be a valuable
      supplement to the reversed-phase LC-MS/MS.

PMID- 14581063
TI  - Stereospecific high-performance liquid chromatographic analysis of ibuprofen in
      rat serum.
AB  - A simple, rapid and sensitive high-performance liquid chromatographic method was
      developed for determination of ibuprofen, (+/-)-(R, S)-2-(4-isobutylphenyl)
      propionic acid, enantiomers in rat serum. Serum (0.1 ml) was extracted with 2,2,4
      trimethylpentane/isopropanol (95:5, v/v) after addition of the internal standard,
      (S)-naproxen, and acidification with H(2)SO(4). Enantiomeric resolution of
      ibuprofen was achieved on ChiralPak AD-RH column with ultraviolet (UV) detection
      at 220 nm without interference from endogenous co-extracted solutes. The
      calibration curve demonstrated excellent linearity between 0.1 and 50 microg/ml
      for each enantiomer. The mean extraction efficiency was >92%. Precision of the
      assay was within 11% (relative standard deviation (R.S.D.)) and bias of the assay
      was lower than 15% at the limit of quantitation (0.1 microg/ml). The assay was
      applied successfully to an oral pharmacokinetic study of ibuprofen in rats.

PMID- 14581064
TI  - Development and validation of a liquid chromatographic method for in vitro
      mupirocin quantification in both skin layers and percutaneous penetration
      studies.
AB  - A simple, rapid, and sensitive reversed-phase high-performance liquid
      chromatographic (HPLC) method for the measurement of mupirocin concentrations in
      both skin layers and percutaneous samples has been developed. Mupirocin was
      extracted from skin layers using PBS-acetonitrile (90:10, v/v). The method is
      sufficiently sensitive and repeatable to be used in percutaneous penetration
      studies. The samples were chromatographed on a 250 mm x 4 mm C(8) LiChrospher
      Select B (5 microm). The mobile phase composition was a mixture of acetonitrile
      ammonium acetate 0.05 M (27.5:72.5, v/v) adjusted to pH 6.3 with acetic acid. The
      analyte was detected at 228 nm and the run time was 11 min. Linearity was
      confirmed in the concentration range 0.2-20 microg/ml and the limit of detection
      was 9.5 ng/ml.

PMID- 14581065
TI  - Improvement and validation of a liquid chromatographic method for the
      determination of levosulpiride in human serum and urine.
AB  - A rapid, selective and highly sensitive reversed-phase high-performance liquid
      chromatography (HPLC) method was developed for the determination of
      levosulpiride, 5-(aminosulfonyl)-N-[(1-ethyl-2-pyrrolidinyl)methyl]-2-methoxy
      benzamide, in human serum and urine. The method involved the extraction with a
      dichloromethane followed by back-extraction into 0.025 M sulfuric acid. HPLC
      analysis was carried out using reversed-phase isocratic elution with a Luna
      C(18)(2) 5 microm column, a mobile phase of acetonitrile-0.01 M potassium
      hydrogen phosphate (30:70, v/v, adjusted to pH 8.5 with triethylamine), and a
      fluorescence detector with excitation at 300 nm and emission at 365 nm. The
      chromatograms showed good resolution and sensitivity and no interference of human
      serum and urine. The calibration curves were linear over the concentration range
      0.25-200 ng/ml for serum and 0.2-20 microg/ml for urine with correlation
      coefficients greater than 0.997. Intra- and inter-day assay precision and
      accuracy fulfilled the international requirements. The mean absolute recovery for
      human serum was 89.8+/-3.7%. The lower limits of quantitation in human serum and
      urine were 0.25 ng/ml and 0.2 microg/ml, respectively, which were sensitive
      enough for pharmacokinetic studies. Stability studies showed that levosulpiride
      in human serum and urine was stable during storage, or during the assay
      procedure. This method was successfully applied to the study of pharmacokinetics
      of levosulpiride in human volunteers following a single oral administration of
      levosulpiride (25 mg) tablet.

PMID- 14581066
TI  - Metabolism of the new designer drug alpha-pyrrolidinopropiophenone (PPP) and the
      toxicological detection of PPP and 4'-methyl-alpha-pyrrolidinopropiophenone
      (MPPP) studied in rat urine using gas chromatography-mass spectrometry.
AB  - R,S-alpha-pyrrolidinopropiophenone (PPP) is a new designer drug with assumed
      amphetamine-like effects which has appeared on the illicit drug market. The aim
      of this study was to identify the PPP metabolites using solid-phase extraction,
      ethylation or acetylation as well as to develop a toxicological detection
      procedure in urine using solid-phase extraction, trimethylsilylation and gas
      chromatography-mass spectrometry (GC-MS). Analysis of urine samples of rats
      treated with PPP revealed that PPP was extensively metabolized by hydroxylation
      of the pyrrolidine ring with subsequent dehydrogenation to the corresponding
      lactam, hydroxylation of the aromatic ring in position 4' or double dealkylation
      of the pyrrolidine ring to the corresponding primary amine (cathinone) partly
      followed by reduction of the keto group to the corresponding secondary alcohol
      (norephedrines). As cathinone and the norephedrine diastereomers are also formed
      after intake of other drugs of abuse or medicaments, special attention must be
      paid to the detection of the unequivocal metabolite 2"-oxo-PPP as an unambiguous
      proof for the intake of PPP. The hydroxy groups were found to be partly
      conjugated. Based on these data, PPP could be detected in urine via its
      metabolites by full-scan GC-MS using mass chromatography for screening and
      library search for identification by comparison of the spectra with reference
      spectra. The same toxicological detection procedure can be applied to other
      designer drugs of the pyrrolidinophenone type, like MOPPP, MDPPP, MPHP, and MPPP.
      The detection of the latter will also be presented here.

PMID- 14581067
TI  - Analysis of the progesterone displacement of its human serum albumin binding site
      by beta-estradiol using biochromatographic approaches: effect of two salt
      modifiers.
AB  - The mechanisms of (i) the binding of two sex-hormones (i.e. progesterone and beta
      estradiol) to human serum albumin (HSA) and (ii) the progesterone displacement of
      its HSA binding cavity by beta-estradiol were studied by biochromatography using
      three different methods. In the first time, zonal elution method was used to
      prove the direct competition effect between the two sex-hormone. In the second
      time, the competition effect between beta-estradiol and progesterone to bound on
      the same HSA site was analysed by the competitive bi-Langmuir approach. Finally,
      the thermodynamic data of these two binding processes were studied. The Gibbs
      free energy value (Delta(approximately)G degrees) of the displacement equilibrium
      was negative demonstrating that beta-estradiol displaced progesterone of its HSA
      binding cavity. Moreover, the effect of two chloride modifiers (i.e. Na(+),
      Mg(2+)) on these two binding processes were analysed. Results showed that in the
      salt biological concentration ranges, the Mg(2+) cation enhanced strongly the
      bioavailable progesterone, whereas the Na(+) cation interacted slowly on the
      progesterone displacement of its HSA binding site by beta-estradiol. This study
      showed that it must be useful to carry out more in vivo test on the magnesium
      supplementation effect for women who suffer from estrogen dominance syndrome.

PMID- 14581068
TI  - Novel inhibition of cis/trans retinoic acid interconversion in biological fluids-
      an accurate method for determination of trans and 13-cis retinoic acid in
      biological fluids.
AB  - All-trans retinoic acid (tRA, or tretinoin) can be metabolized through
      stereoisomerization to 13-cis retinoic acid (13-cRA) in vivo. We have developed a
      simple, sensitive and accurate method for analyzing tRA and 13-cRA in plasma with
      the addition of N-ethylmaleimide (NEM) and Vitamin C (Vit. C) to prevent the
      interconversion of cis/trans retinoic acid. All-trans RA, 9-cRA, and 13-cRA were
      well separated from each other in plasma by using a C18 precolumn and a column
      with a gradient solvent system of mobile phases A and B at a flow rate of 1.0
      ml/min. In addition, thermal stability of tRA and cRA in plasma during the sample
      preparation under the temperature of 0 and 25 degrees C were studied. Our results
      showed that (1) the interconversion ratios (%) (cRA/tRA and tRA/cRA) were
      decreased with the addition of NEM and Vit. C and the minimum concentrations of
      NEM and Vit. C to inhibit the interconversion were 50 and 150 microM,
      respectively, (2) higher concentrations of NEM and Vit. C were required to
      prevent the interconversion at higher temperature, (3) the precision and accuracy
      of calibration curve with various concentration of tRA (1-1000 ng/ml) and 13-cRA
      (5-800 ng/ml) in plasma showed good linearity (r(2)=0.9992 and 0.9994), and
      between-day errors expressed by coefficient of variation (CV, %) for tRA and 13
      cRA which were both less than 5.6%, (4) the mean recovery of the analytes were 78
      94% for tRA and 80-92% for 13-cRA at concentration range from 1 to 1000 ng/ml and
      5 to 800 ng/ml, respectively, and (5) the limit of quantitation of tRA and 13-cRA
      were 1 and 5 ng/ml, respectively. In addition, the HPLC method had been
      successfully applied to the tRA pharmacokinetic study in two hepatoma patients
      after receiving 45 mg/m(2) per day orally. Thus, our results suggest that the
      HPLC method for analyzing tRA and 13-cRA in plasma with the addition of NEM and
      Vit. C is a simple, sensitive and accurate method.

PMID- 14581069
TI  - Liquid chromatography-electrospray mass spectrometry (LC-MS) method for
      determination of esmolol concentration in human plasma.
AB  - Esmolol is a very short-acting beta-blocker commonly used in critically ill
      patients. To study the pharmacokinetics of esmolol in pediatric patients, a
      liquid chromatography-electrospray mass spectrometry (LC-MS) method to quantitate
      esmolol concentration in plasma was developed. Following methylene chloride
      extraction from 200 microl aliquots of plasma containing internal standard and
      reconstitution in 0.05% formic acid, 10 microl are injected onto column, eluted
      using a methanol/formic acid gradient over 15 min, and monitored with selected
      ion recording at 296.2 and 282.2. The assay is linear between 2 and 1000 ng/ml.
      The intra-day and inter-day coefficients of variation are less than 8 and 10%,
      respectively.

PMID- 14581070
TI  - Determination of nicotine and its metabolites in urine by solid-phase extraction
      and sample stacking capillary electrophoresis-mass spectrometry.
AB  - The combination of capillary electrophoresis (CE) and mass spectrometry (MS) with
      solid-phase extraction (SPE) has been used for the identification of nicotine and
      eight of its metabolites in urine. The recovery of cotinine from cotinine-spiked
      urine, by C18 SPE, was found to be 98%. Smokers urine (200 ml) was
      preconcentrated 200-fold via SPE prior to analysis. The sample stacking mode of
      CE, when compared to capillary zone electrophoresis, was shown to improve peak
      efficiency by 132-fold. The combination of hydrodynamic and electrokinetic
      injection was studied with sample stacking/CE/MS. The on-column limits of
      detection (LOD) of nicotine and cotinine, by this technique, were found to be
      0.11 and 2.25 microg/ml, respectively. Hence, LODs of nicotine and cotinine in
      urine after 200-fold preconcentration were 0.55 and 11.25 ng/ml, respectively.

PMID- 14581071
TI  - Purification and properties of extracellular dextranase from a Bacillus sp.
AB  - Bacterial strains in the genus Bacillus were isolated from natural soil samples
      and screened for production of extracellular dextranases (E.C.3.2.1.11). One
      strain, determined by 16sRNA analysis as Paenibacillus illinoisensis exhibiting
      stable dextranase activity, was chosen for further analysis, and the dextranase
      from it was purified 733-fold using salt and PEG precipitations, two-phase
      extraction and DEAE-Sepharose chromatography with a total yield of 19%. The
      purified enzyme had three isoforms, with molecular masses of 76, 89 and 110kDa
      and isoelectric points of 4.95, 4.2 and 4.0, respectively. The mixture of the
      three dextranase isoforms has a broad pH optimum around pH 6.8 and a temperature
      optimum at 50 degrees C. The N-terminal sequence (Ala-Ser-Thr-Gly-Lys) was
      identical between the isoforms. No sequence homology with the known dextranases
      in the protein databanks was found.

PMID- 14581072
TI  - Quantitation of nitric oxide-derived nitrite from activated macrophages using
      microdialysis sampling.
AB  - An HPLC method for detecting nitrite in microdialysis samples obtained from
      activated RAW 264.7 macrophages in cell culture has been developed. Nitrite was
      quantified using a pre-column derivatization with 2,4-dinitrophenylhydrazine (2,4
      DNPH) followed by HPLC-UV analysis of the azide product. For dialysates, the
      detection limit of nitrite was 750 nM and the quantitation limit was 2.5 microM.
      The microdialysis relative recovery of nitrite in the macrophage cell culture
      medium was determined to be 86+/-2% (n=3) at a flow rate of 0.7 microl/min.
      Nitrite produced from activated macrophages was measured immediately after
      lipopolysaccharide (LPS) stimulation using microdialysis sampling.

PMID- 14581073
TI  - Sensitive and rapid isocratic liquid chromatography method for the quantitation
      of curcumin in plasma.
AB  - An HPLC assay was developed using three methods of plasma sample preparation in
      order to quantitate curcumin, the main constituent in the herbal dietary
      supplement turmeric. Each method involves simple and rapid processing of samples
      (either an ethyl acetate or chloroform extraction) with resulting different
      quantitation limits for curcumin. The assay was developed in an effort to
      quantify extremely low curcumin plasma concentrations observed in preliminary in
      vivo studies. The most sensitive assay can reliably detect concentrations down to
      2.5 ng/ml. Plasma quantitation was precise and accurate based on both intra- and
      inter-day validations as indicated by low values for coefficients of variation
      and bias, respectively (< or =15%). The analytical validation was reproducible
      between different analysts. The resulting analytical method couples desired
      sensitivity with the ease of an isocratic system.

PMID- 14581074
TI  - Development and validation of a liquid chromatography-tandem mass spectrometry
      method for the determination of pyridostigmine bromide from guinea pig plasma.
AB  - An HPLC/MS/MS method was validated for the low level analysis of pyridostigmine
      bromide (PB) from guinea pig plasma. An advantage of this strong-cation exchange
      HPLC/MS/MS method was the enhancement of the ESI-MS signal by providing good
      retention and good peak shape of PB with a mobile phase of 70% acetonitrile. In
      addition, the use of 70% acetonitrile in the mobile phase allowed the direct
      injection of the supernant from the protein precipitated extracted sample. The
      assay was linear from the range of 0.1 to 50 ng/ml using only 25 microl of
      sample. The precision and accuracy of the assay was better than 9.1 and 113%,
      respectively.

PMID- 14581075
TI  - Quantitative determination of the enantiomers of methadone and its metabolite
      (EDDP) in human saliva by enantioselective liquid chromatography with mass
      spectrometric detection.
AB  - A sensitive enantioselective liquid chromatographic assay with mass spectrometric
      detection (LC-MS) has been developed and validated for the simultaneous
      determination of saliva concentrations of (R)- and (S)-methadone (Met) and (R)-
      and (S)-2-ethylidene-1,5-dimethyl-3,3-diphenyl-pyrrolidine (EDDP, a primary
      metabolite of Met). Saliva specimens were collected using Salivette devices
      (Sarsedt), and centrifuged; collected saliva was then spiked with deuterated
      internal standards, D3-Met and D3-EDDP, and directly injected into the LC-MS.
      Enantioselective separations were achieved on a liquid chromatographic chiral
      stationary phase (CSP) based upon immobilized alpha(1)-acid glycoprotein (AGP)
      using a mobile phase composed of acetonitrile: ammonium acetate buffer (10mM, pH
      7.0) in a ratio of 18:82 (v/v), a flow rate of 0.9 ml/min and a temperature of 25
      degrees C. Under these conditions, enantioselective separations were observed for
      methadone (alpha=1.30) and EDDP (alpha=1.17) within 15 min. Met, EDDP, D3-Met and
      D3-EDDP were detected using selected ion monitoring at m/z 310.20, 278.20, 313.20
      and 281.20, respectively. Linear relationships between peak height ratio and drug
      enantiomer concentrations were obtained for methadone in the range of 5.0-600.0
      ng/ml, and for EDDP from 0.5 to 15.0 ng/ml per enantiomer with correlation
      coefficients better than 0.9994, where lower limit of quantification (LLOQ) for
      Met was 5 ng/ml and for EDDP 0.5 ng/ml. Acceptable intra- and inter-day precision
      of the method (CVs<4.0%) and accuracy (CVs<4.0%) were obtained. These findings
      demonstrate the accuracy and precision of the method used to successfully analyze
      saliva obtained from patients enrolled in a methadone-maintenance program.

PMID- 14581076
TI  - Liquid chromatographic method with ultraviolet absorbance detection for
      measurement of levamisole in chicken tissues, eggs and plasma.
AB  - The development and validation of a high-performance liquid chromatographic and
      UV detection method was accomplished for quantitative determination of levamisole
      in chicken tissues, eggs and plasma. The chromatographic separation was achieved
      on Luna 5 microm C(18) column using a mobile phase of 0.2% acetic acid in
      water:methanol (50:50 (v/v)) and Pic B-7 low UV reagent and the pH was adjusted
      to 7.31 with ammonium hydroxide and UV wavelength was 225 nm. Limits of
      quantification were 0.025 microg/g for all tissues and 0.003 microg/ml for
      plasma. Limit of detection was 0.001 microg/g for tissues and plasma.

PMID- 14581077
TI  - Characterization of metallothionein isoforms from rabbit liver by liquid
      chromatography coupled to electrospray mass spectrometry.
AB  - Metallothioneins (MTs), a group of low molecular weight proteins found in
      practically all life forms, are characterized by high sulfur content and an
      affinity for metal ions. At acidic pH, MTs show metal depletion, leading to
      apothioneins. In the work described here, in order to optimize the separation of
      rabbit liver apothioneins using liquid chromatography (LC) with UV detection, the
      proportion of the organic modifier of the mobile phase was optimized by
      establishing relationships between Reichardt's E(N)(T) scale of solvent polarity
      and the chromatographic retention measured by the capacity factor, k.
      Additionally, such optimum separations were carried out in a LC-electrospray mass
      spectrometry (ES-MS) coupled system allowing the identification and
      characterization of the different rabbit liver apo-MT-forms. In this way,
      electrospray ionization mass spectrometry offers great possibilities aiming at a
      better understanding of metallothionein polymorphism.

PMID- 14581078
TI  - Determination of tiropramide in human plasma by liquid chromatography-tandem mass
      spectrometry.
AB  - A rapid, sensitive and selective liquid chromatography-tandem mass spectrometric
      (LC/MS/MS) method for the determination of tiropramide in human plasma was
      developed. Tiropramide and internal standard, cisapride were extracted from human
      plasma by liquid-liquid extraction and analyzed on a Luna C8 column with the
      mobile phase of acetonitrile-ammonium formate (10mM, pH 4.5) (50:50, v/v). The
      analytes was detected using an electrospray ionization tandem mass spectrometry
      in the multiple-reaction-monitoring mode. The standard curve was linear (r=0.998)
      over the concentration range of 2.0-200 ng/ml. The intra- and inter-assay
      coefficients of variation ranged from 2.8 to 7.8 and 6.7 to 8.9%, respectively.
      The recoveries of tiropramide ranged from 50.2 to 53.1%, with that of cisapride
      (internal standard) being 60.9+/-5.3%. The lower limit of quantification for
      tiropramide was 2.0 ng/ml using 100 microl plasma sample. This method was applied
      to the pharmacokinetic study of tiropramide in human.

PMID- 14581079
TI  - Quantitative analysis of dipeptidyl peptidase inhibitor P32/98 and its main
      metabolite in rat, dog, mouse, monkey, human plasma and human urine using liquid
      chromatography-tandem mass spectrometry: application to pharmacokinetic
      evaluation.
AB  - A sensitive, specific and robust assay was developed for the simultaneous
      determination of the oral antidiabetic drug candidate P32/98 and its main
      metabolite P57/99 in different biological fluids using LC-MS/MS in the
      atmospheric pressure chemical ionization (APCI) positive mode. Both analytes were
      isolated from the biological matrices by solid phase extraction using a strong
      cation exchanger. This assay was successfully cross-validated for rat, dog,
      mouse, monkey, human plasma and human urine. The pre-study validation results, as
      well as the in-study quality control (QC) data obtained, demonstrate the
      feasibility of the assay for pharmacokinetic evaluation of the compounds in
      different species and confirm the robustness of the assay for routine use.

PMID- 14581080
TI  - Enantioselective determination of ibuprofen in plasma by high-performance liquid
      chromatography-electrospray mass spectrometry.
AB  - The enantioselective analysis of ibuprofen (IBU), a chiral nonsteroidal anti
      inflammatory drug, in human plasma was carried out by high-performance liquid
      chromatography (HPLC)-mass spectrometry (LC-MS-MS). The plasma samples were
      prepared by liquid-liquid extraction using hexane:ethyl acetate (8:2, v/v). The
      HPLC chiral resolution of IBU was obtained using a chiral stationary phase based
      on a tris-(3,5-dimethylphenylcarbamate) amylose derivative, under reversed phase
      conditions (CHIRALPAK AD-RH column), using a mobile phase consisting of
      methanol:water (8:2, v/v), containing 0.1% of an aqueous solution of phosphoric
      acid at pH 2, at a flow rate of 0.6 ml/min. A make-up liquid of 4.5% (w/v)
      NH(4)OH aqueous solution was used to assure optimum electrospray ionization in
      the negative mode. The coefficients of variation and deviation from nominal
      values were lower than 15% for both within- and between-day assays. The
      quantitation limit was 0.12 microg/ml and the linear range was 0.12-90.0
      microg/ml for both enantiomers. The method proved to be suitable for single dose
      pharmacokinetic studies.

PMID- 14581081
TI  - Optimized glucuronide hydrolysis for the detection of psilocin in human urine
      samples.
AB  - In order to develop a sensitive and reliable analytical method for psilocin (PC)
      in urine samples, the hydrolysis conditions including the acid, alkaline and
      enzymatic hydrolyses have been investigated by monitoring not only PC but also
      psilocin glucuronide (PCG) by liquid chromatography tandem mass spectrometry (LC
      MS-MS); PCG was initially identified in a "magic mushroom (MM)" user's urine by
      liquid chromatography mass spectrometry (LC-MS) and LC-MS-MS. The proposed
      conditions optimized for the hydrolysis are as follows: hydrolysis, enzymatic
      hydrolysis; enzyme, Escherichia coli beta-glucuronidase (5000 units/ml urine);
      incubation, pH 6 at 37 degrees C for 2h. The complete hydrolysis of PCG in urine
      was obtained under these conditions, while the enzymatic hydrolyses with three
      types of beta-glucuronidases originated from bovine liver (Type B-1), Helix
      pomatia (Type H-1) and Ampullaria provided uncompleted hydrolysis of PCG. Also,
      neither the acid nor alkaline hydrolysis was found to be applicable. According to
      the present method, 3.55 microg/ml of psilocin was detected in the "magic
      mushroom" user's urine after the enzymatic hydrolysis, though psilocin was not
      detected without hydrolysis.

PMID- 14581082
TI  - Enantioselective determination of lercanidipine in human plasma for
      pharmacokinetic studies by normal-phase liquid chromatography-tandem mass
      spectrometry.
AB  - We describe here the first method for the enantioselective analysis of the
      calcium antagonist lercanidipine in human plasma by high performance liquid
      chromatography (HPLC) employing tandem mass spectrometric (MS) detection. Routine
      determination of lercanidipine enantiomers in human plasma in the working range
      of 0.025-50.0 ng ml(-1) plasma for each enantiomer with an accuracy and precision
      less than 15% was possible. Application of the method to a stereospecific study
      of the pharmacokinetics showed that plasma levels after an oral dose of rac
      lercanidipine administered to a healthy volunteer were found to be higher for the
      (S)-enantiomer.

PMID- 14581083
TI  - Determination of scutellarin in rat plasma by high-performance liquid
      chromatography with ultraviolet detection.
AB  - A validated high-performance liquid chromatography method is described for the
      determination of scutellarin in rat plasma using a liquid-liquid extraction and
      ultraviolet (UV) absorbance detection. The separation used a Diamonsil ODS column
      (250 mm x 4.6mm i.d., 5 microm particle size) with an isocratic mobile phase
      consisting of methanol-acetonitrile-50mM dihydrogen ammonium phosphate buffer
      (22:15:63 (v/v/v), adjusted to pH 2.5 with 1M phosphoric acid). The ultraviolet
      detector operated at 335 nm. Plasma samples were extracted with ethyl acetate
      after acidification. The extraction recovery of scutellarin ranged from 68.1 to
      80.5%. High selectivity and a low quantitation limit (0.050 microg/ml) were
      achieved. The linear range was 0.050-12.5 microg/ml, correlation coefficient
      r=0.9981. The method has a good reproducibility, R.S.D. values were below 7.9%
      for within-day and between-day precision. The method is simple, rapid, and
      applicable to preliminary pharmacokinetic studies of scutellarin in rats.

PMID- 14581084
TI  - Beta emitter systems and results from clinical trials. state of the art.
AB  - Vascular brachytherapy has been established as the standard of care for the
      treatment of in-stent restenosis (ISR). Both beta and gamma emitters are
      currently in use for the prevention of ISR recurrence. The use of beta sources
      for vascular application is attractive from both the radiation exposure and
      safety points of view, and a wide variety of beta sources are available for this
      application. This review is intended to summarize the clinical trials utilizing
      beta emitter systems for the treatment of ISR and de novo lesions and their
      subsequent results.

PMID- 14581085
TI  - 32P liquid sources--comparison of the effectiveness of postangioplasty versus
      poststenting intravascular brachytherapy in hypercholesterolemic rabbits.
      Adjunctly implanted titanium stent does not attenuate the effect of endovascular
      irradiation.
AB  - PURPOSE: Endovascular application of ionizing radiation is a promising but still
      not sufficiently studied means of restenosis prevention. To test the effects of
      radiation on restenosis, and especially their dependence on whether the
      angioplasty was followed by stent implantation or not, we performed an in-stent
      versus no-stent intravascular brachytherapy study in an animal model. Balloon
      based, continuous and self-centering, liquid 32P sources seemed the most
      convenient for the purpose. METHOD: The radial dose distribution around
      angioplasty balloons filled with solutions of Na(2)H32PO(4) was calibrated by
      thermoluminescence dosimetry, both in the absence and presence of stents. The
      animal experiments were performed on rabbits with induced hypercholesterolemia.
      The balloons containing 32P were introduced into iliac artery immediately after
      stent implantation or after angioplasty alone. Radiation effects were evaluated
      postmortem by comparing thickness of various components of the artery wall.
      RESULTS: In the presence of titanium stents (TTS), irradiation with 16 Gy dose at
      1.0 mm from the balloon surface was no less effective in reducing hypertrophy in
      every active layer of the artery wall than without a stent. CONCLUSION: In the
      animal model, IVBT basing on P(32) liquid sources was no less effective in the
      stented arteries than in the nonstented ones.

PMID- 14581086
TI  - Coagulation factor Xa synergistically interacts with serotonin in inducing
      vascular smooth muscle cell proliferation.
AB  - INTRODUCTION: Initial events following vascular interventions include activation
      of platelets and coagulation cascade. Activated platelets release several
      vasoactive mediators including serotonin. Activation of coagulation cascade
      results in conversion of inactive zymogens such as factor X to its active form
      (factor Xa). So this study designed to examine the effect of factor Xa on rabbit
      vascular smooth muscle cell (VSMC) proliferation and its interaction with
      serotonin. METHODS: Growth-arrested VSMCs were incubated in a serum-free medium
      with different concentrations of factor Xa with or without serotonin. VSMC
      proliferation was examined by increase in incorporation of [3H]thymidine into DNA
      and by increase in cell number. RESULTS: Factor Xa and serotonin stimulated DNA
      synthesis in a dose-dependent manner. Factor Xa had a maximal effect at 100 nM
      (1180+/-110%) and serotonin at 50 microM (345+/-21%). When added together, at
      nonmitogenic concentrations, factor Xa (0.1 nM) and serotonin (1 micoM)
      synergistically induced DNA synthesis (312+/-12%). These increases in DNA
      synthesis were paralleled by an increase in cell number. Serine protease
      inhibitors, active site blockers and platelet-derived growth factor receptor
      tyrosine kinase inhibitor blocked the mitogenic effect of factor Xa and its
      interaction with serotonin. Similarly, serotonin type 2 receptor inhibitor and Gi
      protein-coupled receptor inhibitor inhibited the mitogenic effect of serotonin
      and its interaction with factor Xa. When used in combination, they blocked the
      interaction between factor Xa and serotonin. CONCLUSION: Coagulation factor Xa
      and serotonin are mitogenic to VSMCs and also function as amplification factors
      to each other, suggesting that inhibition of neointimal proliferation after
      vascular injury may require the combined use of multiple growth factor inhibitors
      to simultaneously block several critical cellular activation pathways.

PMID- 14581087
TI  - Fabrication of drug-eluting covered stents with micropores and differential
      coating of heparin and FK506.
AB  - To reduce in-stent restenosis rates, we developed a novel drug-eluting covered
      stent with a microporous elastometric covered film, in which its luminal surface
      was flat and immobilized with heparin for anticoagulation and its outer surface
      immobilized with FK506 to prevent neointimal hyperplasia. One month after
      implantation into the bilateral common carotid arteries, all stented arteries
      were patent and the luminal surfaces were fully covered with a confluent of
      endothelial cells irrespective of the drug immobilization. In the control group,
      which consisted of covered stents without drug immobilization, intensive
      inflammatory cells adjacent to the stents and neointimal hyperplasia, indicating
      vascular injury, were observed. In contrast, in the developed drug-eluting
      stents, only a few inflammatory cells around the stent strut and covered film
      were observed, and there was no significant neointimal thickening.

PMID- 14581088
TI  - Feasibility study and dosimetric assessment of radiolabeled drugs injected to the
      coronary arterial wall to prevent restenosis.
AB  - PURPOSE: Intramural delivery of a P-32 radiolabeled oligonucleotide (ODN) using
      an infiltrating catheter has been proposed recently to potentially reduce
      restenosis in coronary arteries and tested on a limited number of human subjects.
      However, because of the low efficiency of drug retention (approximately 2-5%)
      after the initial washout period from this technique, the dose levels to
      nontarget organs may be significant and thus may require a detailed
      investigation. The radiation dose distributions resulting from this technique is
      investigated using the MIRD formalism and Monte Carlo calculations. MATERIALS AND
      METHODS: The total activity of the P-32 ODN to be injected during treatment to
      deliver a therapeutic dose of approximately 30 Gy to the arterial wall is
      estimated taking into account the drug delivery efficacy of the infiltrating
      device (approximately 2-5% typical). Using pharmacokinetic data for P-32 ODN, we
      estimate the dose to healthy organs resulting from the systemic fraction that is
      released into the circulatory system during washout (>95% typical). Variabilities
      in the biological parameters are also identified as important sources of error in
      the prescribed dose. RESULTS: A limitation to this technique is the poor accuracy
      in delivering the prescribed dose due to variability in the amount of drug
      delivered. Dose to organs is also an important limitation. For example, our
      calculation indicate that approximately 37 MBq (1 mCi) of P-32 labeled ODN are
      needed to deliver 30 Gy to the arterial wall assuming a delivery efficiency of 2
      5% and a 24-h residence time. This may result in doses of approximately 1 Gy to
      the spleen and 0.2-0.4 Gy to the liver, kidneys and lungs (95% confidence
      interval). CONCLUSION: This novel therapy suffers from serious limitations. It is
      doubtful that a therapeutic dose can be delivered accurately, safely and
      effectively to the arterial wall because of the poor delivery efficacy and
      extreme variability found in drug delivery experiments. Also, dose levels to
      healthy organs appears to be too high to recommend the use of this technique in
      human experiments.

PMID- 14581089
TI  - Dosimetry for an Sr90/Y90 source train used for intravascular radiation of a
      hemodialysis graft.
AB  - OBJECTIVE: Vascular access for hemodialysis is often achieved with an arterial
      venous graft (AVG). Brachytherapy is being explored for prevention of stenosis
      within these grafts. The objective was to develop treatment planning (TP)
      capability for dialysis implants. MATERIALS AND METHODS: Fluoroscopic images are
      used to identify position of sources and irradiated vessel. An Sr(90)/Y(90) beta
      source, jacketed in a CO(2)-filled balloon, is used to irradiate the AVG. A
      single-seed Sr(90) dose kernel was generated using Monte Carlo. The single-seed
      dose kernel was employed to calculate the dose surrounding the implant accounting
      for the path length of the beta particles through the gas-filled balloon.
      RESULTS: Dose distributions are displayed superimposed on the fluoroscopic image
      of the AVG. Dose-area histograms were also generated. CONCLUSION: TP for dialysis
      implants can be performed using radiographic localization of the graft. The TP
      tools could be used to correlate clinical outcome with dose delivery.

PMID- 14581090
TI  - The challenge of staphylococcal pacemaker endocarditis in a patient with
      transposition of the great arteries endocarditis in congenital heart disease.
AB  - Staphylococcus aureus is a leading cause of septicaemia and infective
      endocarditis. The overall incidence of staphylococcal bacteraemia is increasing,
      contributing to 16% of all hospital-acquired bacteraemias. The use of cardiac
      pacemakers has revolutionized the management of rhythm disturbances, yet this has
      also resulted in a group of patients at risk of pacemaker lead endocarditis and
      seeding in the range of 1% to 7%. We describe a 26-year-old man with
      transposition of the great arteries who had a pacemaker implanted and presented
      with S. aureus septicaemia 2 years postpacemaker implantation and went on to
      develop pacemaker lead endocarditis. This report illustrates the risk of
      endocarditis in the population with congenital heart disease and an intracardiac
      device.

PMID- 14581091
TI  - Stent-based immunosuppressive therapies for the prevention of restenosis.

PMID- 14581092
TI  - A morphological-mechanical explanation of edge restenosis in lesions treated with
      vascular brachytherapy.
AB  - PURPOSE: Edge restenosis in stenotic lesions treated by implantation of a
      conventional stent followed (or preceded) by a catheter-based brachytherapy is
      often attributed to "geographic miss" (GM). We propose a complementary (or,
      possibly, alternative) explanation based on the concept that a clear
      postprocedural mismatch between the in-stent lumen and the normal (undilated)
      lumens of the proximal and/or distal vessel segments results in an excessive,
      damageable increase of axial wall stress in these segments. METHODS: The possible
      poststenting situations at both margins of a stent are examined, and based on the
      presence or absence of an increase in axial wall stress, predictions are made
      about the lesion evolution. The concept is then also examined in the light of
      published observations. RESULTS: None of the analyzed observations appeared to be
      incompatible with the proposed morphological-mechanical explanation. CONCLUSION:
      From a mechanical point of view, optimal matching of the proximal and distal
      stent diameters to the corresponding normal diameters of the adjacent arterial
      segment is likely to reduce the rate of edge restenosis.

PMID- 14581093
TI  - Suffering and adaptation to cancer. What to measure and when to intervene.

PMID- 14581094
TI  - Cancer distress screening. Needs, models, and methods.
AB  - The idea of screening for distress in oncology populations is not new. Many
      recommendations have been made regarding the need for routine screening, and
      methods have been suggested for accomplishing this. However, a synthesis of this
      body of research is not readily available. This paper summarizes the literature
      documenting the levels of distress commonly found in cancer patients, followed by
      discussion of recommended standards for routine distress screening, and a summary
      of various programs that have attempted to establish clinical screening programs.
      The computerized quality of life (QL) screening literature is also briefly
      reviewed as potentially instructive. This review is followed by a theoretical and
      psychometric assessment of the various screening instruments and screening models
      that have been suggested in the literature or used clinically and a brief
      assessment of possible economic costs of psychosocial screening, ending with
      concrete suggestions for methods and models that could be widely adopted by
      psychosocial oncology programs.

PMID- 14581095
TI  - Symptomatic distress, hopelessness, and the desire for hastened death in
      hospitalized cancer patients.
AB  - OBJECTIVE: This study evaluated the desire for hastened death (DHD) in cancer
      patients at varying stages of disease to determine its frequency and relationship
      to physical and psychological distress. METHODS: Two hundred twenty-four
      inpatients at Princess Margaret Hospital completed questionnaires assessing pain,
      physical symptoms, depression, hopelessness, and DHD. RESULTS: There was
      significant physical and psychological distress in this sample with a mean of
      nine physical symptoms reported by each subject. Seven percent reported moderate
      DHD on the Schedule of Attitudes Towards Hastened Death (SAHD) and 2% reported
      high DHD. Hopelessness and stage of disease were the only significant independent
      predictors of DHD and their interaction was associated with increased DHD.
      Hopelessness and, less so, depression both mediated the pathways between illness
      related factors and DHD. CONCLUSIONS: Findings suggest that DHD is significantly
      related to hopelessness and advancing disease. Assessment of this phenomenon
      prior to the end of life may provide opportunities for intervention.

PMID- 14581096
TI  - Self-concept as a "BMT patient", illness intrusiveness, and engulfment in
      allogeneic bone marrow transplant recipients.
AB  - OBJECTIVE: The experience of cancer and its treatment by bone marrow
      transplantation (BMT) can enhance the salience of one's status as a patient in
      the evolution of self-concept. Illness and the patient role can come to dominate
      the sense of self, resulting in feelings of hopelessness, helplessness, and
      distress ("engulfment"). Illness-induced lifestyle disruptions ("illness
      intrusiveness") introduce adaptive demands, challenging preexisting conceptions
      of self. Illness intrusiveness and engulfment may interact, leading affected
      individuals to construe themselves as highly similar to a prototypical "BMT
      patient". METHODS: Ninety allogeneic BMT outpatients completed the Illness
      Intrusiveness Ratings Scale, Modified Engulfment Scale, and a semantic
      differential measure of self-concept as a BMT patient in an interview context.
      RESULTS: Illness intrusiveness correlated significantly with engulfment (r=.58,
      P<.0001) and with self-concept as a BMT patient (r=.27, P<.016). Engulfment did
      not correlate significantly with self-concept as a BMT patient (r=.15). Multiple
      regression analysis, controlling for relevant covariates, indicated a significant
      Illness Intrusiveness x Engulfment interaction effect on self-concept as a BMT
      patient [F(1,84)=4.93, P<.029]. CONCLUSIONS: Self-concept as a BMT patient
      increases as cancer and its treatment introduce increasing lifestyle disruptions
      (illness intrusiveness). These effects are amplified when self-experience is
      dominated by disease and treatment and patients feel helpless, hopeless, and
      distressed (engulfment).

PMID- 14581097
TI  - The experience of loss and anticipation of distress in colorectal cancer patients
      undergoing genetic testing.
AB  - OBJECTIVE: The purpose of this paper is to describe pretest psychological
      functioning in a sample of colorectal cancer (CRC) patients undergoing genetic
      testing. We also explored the relationship among demographic, medical, family
      history and loss variables and current pretest distress, and those related to
      anticipated posttest distress. METHODS: This paper reports pretest findings from
      a prospective, longitudinal psychosocial survey. Data are presented on 220 CRC
      patients at pretest. RESULTS: We found a subgroup of CRC patients that are
      currently distressed and anticipate becoming depressed if they receive a positive
      genetic test result. There were significant associations among pretest distress,
      family history of CRC and loss related to CRC and anticipation of becoming
      depressed at posttest. CONCLUSIONS: The findings suggest that a subgroup of CRC
      patient's experience or anticipate distress that may warrant attention. Family
      history of CRC and losses related to CRC may be important indicators of posttest
      adjustment.

PMID- 14581098
TI  - Waiting for a breast biopsy. Psychosocial consequences and coping strategies.
AB  - OBJECTIVE: The aim of this pilot/feasibility study was to describe the experience
      of women presenting with a suspicious mammogram who are waiting for a breast
      biopsy and to identify those at risk for distress. METHODS: Participants (n=25)
      were interviewed at two time points: immediately after being put on the waiting
      list (T1) and again immediately before their biopsy approximately 6 weeks later
      (T2). Self-report measures of distress and coping were used. Perceived personal
      risk of a positive biopsy finding and information needs were assessed through
      open-ended questions. RESULTS: Distress levels were high in this sample. Using
      cognitive-avoidant coping strategies, being employed, history of previous
      biopsies, and having a family history of breast cancer were associated with
      greater distress. Perceived personal risk of a positive biopsy finding was
      overestimated in one half of the cases and was correlated with greater distress.
      CONCLUSION: Waiting period between suspicious mammogram and breast biopsy may be
      a time of high distress for many women.

PMID- 14581099
TI  - The hospice patient's primary caregiver. What is their quality of life?
AB  - OBJECTIVE: The purpose of this study was to (1) assess the quality of life (QOL)
      of the primary caregivers of hospice patients and (2) to analyze the ability of
      the hospice staff to accurately judge caregiver QOL. METHODS: A longitudinal
      pilot study of QOL of caregivers of patients entering hospice was undertaken.
      Caregivers and hospice personnel completed numerous questionnaires every 2 weeks
      until patient death. Global QOL and component constructs, as well as the demands
      of illness on the caregiver and profile of moods, were assessed. Simple
      descriptive statistics at each time point and summary measures (area under the
      curve) were calculated to describe the QOL profile of caregivers and staff
      perceptions of the caregivers. Cronbach's alpha coefficient was applied to verify
      tool internal consistency in a hospice population. Correlation coefficients were
      supplemented by Bland-Altman procedures for comparing scales measuring the same
      construct to compare the scores given by caregivers about themselves and staff
      ratings of the caregivers. The study had 80% power to detect an intracase
      difference between caregiver and staff ratings of the caregiver of 0.4 times the
      standard deviation using a two-sided paired t test with a 5% type I error rate.
      RESULTS: Caregiver QOL was relatively high and stable over time. Caregiver's QOL
      was correlated with the patient's overall QOL/hospice staff accurately evaluated
      caregiver QOL. CONCLUSIONS: By drawing attention to issues that affect the
      caregiver, we can improve delivery of hospice care and positively impact QOL for
      both caregiver and patient. Linear analog self-assessment scales are valuable
      tools for hospice staff to assess caregivers.

PMID- 14581100
TI  - Is perceived family support a relevant variable in psychological distress?. A
      sample of prostate and breast cancer couples.
AB  - OBJECTIVE: In this cross-sectional pilot study of couples in whom the man was
      diagnosed with prostate cancer or the woman with breast cancer, the purpose was
      to identify and compare the variables that characterize couples where both
      spouses are in high psychological distress with couples where the psychological
      distress of both spouses is within the normal range. METHODS: Psychological
      distress and perception of family support in 574 individuals (118 consecutive
      prostate cancer patients and their spouses, and 169 randomly selected breast
      cancer patients and their spouses) were assessed using the Brief Symptom
      Inventory (BSI) and the Perceived Family Support (PFS) self-report
      questionnaires. RESULTS: Couples experiencing high psychological distress
      reported lower levels of perceived family support than couples in whom both
      spouses reported normal levels of psychological distress. CONCLUSION: The
      findings support the notion that perceived family support is associated with the
      psychological distress in both patients and spouses.

PMID- 14581101
TI  - Mood disturbance in community cancer support groups. The role of emotional
      suppression and fighting spirit.
AB  - OBJECTIVE: In this cross-sectional study, we tested whether the coping styles of
      emotional suppression and fighting spirit were associated with mood disturbance
      in cancer patients participating in professionally led community-based support
      groups even when demographic, medical, and group support variables were taken
      into account. METHODS: A heterogeneous sample of 121 cancer patients (71% female,
      29% male) completed the Courtauld Emotional Control Scale (CECS), the Mini-Mental
      Adjustment to Cancer Scale (Mini-MAC), a measure of perceived group support, and
      the Profile of Mood States (POMS). RESULTS: Consistent with hypotheses, lower
      emotional suppression and greater adoption of a fighting spirit, in addition to
      older age and higher income, were associated with lower mood disturbance. Gender,
      time since diagnosis, presence of metastatic disease, time in the support group,
      perceived group support, cognitive avoidance, and fatalism were unrelated to mood
      disturbance. CONCLUSION: Expression of negative affect and an attitude of
      realistic optimism may enhance adjustment and reduce distress for cancer patients
      in support groups.

PMID- 14581102
TI  - Improving the psychological care of cancer patients and their relatives. The role
      of specialist nurses.

PMID- 14581103
TI  - Communal coping model of catastrophizing: conceptual model building.

PMID- 14581104
TI  - Is noradrenaline a significant factor in the analgesic effect of antidepressants?

PMID- 14581105
TI  - Gender and laterality differences in thermosensation throughout the perceptible
      range.
AB  - Several studies suggest that females exhibit greater sensitivity to
      experimentally induced thermal pain than males. These investigations have focused
      mainly on the sensory-discriminative rather than the affective aspect of pain.
      Moreover, potential gender differences for the affective components of innocuous
      thermal sensations have yet to be examined. The primary aim of the present study
      was to evaluate gender differences in the sensory and the affective dimensions of
      the entire thermosensory system, including warmth, coolness, heat pain and cold
      pain. The secondary aim was to evaluate laterality differences in these same
      perceptual dimensions and ranges. Twenty healthy females and 20 healthy males
      immersed their hands in water baths maintained at temperatures ranging from 10 to
      47 degrees C, and rated their perceived thermal intensity, (un)pleasantness, and
      pain intensity. There was a progressive growth in the thermal intensity ratings
      as bath temperatures either increased or decreased from the adapting temperature
      of 33 degrees C. No gender differences emerged for these thermal intensity
      ratings. However, a significant sex effect emerged for the pain intensity ratings
      (P<0.01), and a significant sex x temperature interaction for the affective
      ratings (P<0.01). Females provided higher unpleasantness and pain intensity
      ratings for the more extreme temperatures (10, 15 and 47 degrees C), compared to
      males. Moreover, women perceived the milder temperature baths as more pleasant
      than men did. For a given painful temperature, unpleasantness ratings were higher
      than pain intensity ratings. This relationship between unpleasantness ratings and
      pain ratings was not significantly different between the sexes. No laterality
      differences emerged for the thermal intensity ratings. However, perceived pain
      intensity was significantly higher for the left as compared to the right hand
      (P<0.01). Ratings of unpleasantness also tended to be higher for the left vs.
      right hand, but this difference fell just short of statistical significance
      (P=0.06). These findings indicate that sex differences in thermosensory
      perception are not general, but occur only for the painful and affective
      components. Of particular note is the sex difference for affective but not
      intensive ratings of innocuous temperatures, revealing sex differences in thermal
      perception outside the nociceptive system.

PMID- 14581106
TI  - Social environment moderates the association between catastrophizing and pain
      among persons with a spinal cord injury.
AB  - Catastrophizing, or exaggerating the negative consequences of a situation, is
      associated with higher pain intensity, emotional distress, and functional
      disability among persons with chronic pain. According to the 'communal coping'
      model, catastrophizing in persons with pain may function as a social
      communication directed toward obtaining social proximity, support, or assistance.
      We tested the hypothesis, based on this model, that social factors would moderate
      the association between catastrophizing and sensory and affective pain. Seventy
      four persons with a spinal cord injury and chronic pain completed measures of
      catastrophizing, solicitousness, depression, and sensory and affective pain
      before beginning a randomized controlled medication trial. Catastrophizing was
      significantly associated with solicitousness and pain reports. The association
      between catastrophizing and sensory pain scores was stronger for those who lived
      with a spouse or partner than for those who lived with someone else. In addition,
      there was a stronger association between catastrophizing and affective pain for
      those who reported greater solicitousness in their relationship. The results
      provide partial support for the communal coping model of catastrophizing.

PMID- 14581107
TI  - Spouses' and physicians' perceptions of pain severity in older women with
      osteoarthritis: dyadic agreement and patients' well-being.
AB  - This study examined agreement between patients and two role partners (spouses and
      physicians) on patients' pain severity and the relationships between dyadic
      agreement and patients' well-being. We hypothesized that compared to disagreement
      between patients and role partners, dyadic agreement would be related to better
      psychological well-being (more disease-specific self-efficacy and positive
      affect, and less depression). Participants were 114 older women with
      osteoarthritis, their caregiving husbands, and their rheumatologists. Among
      patient-spouse dyads, agreement was associated with better well-being, especially
      when compared to spouses' underestimation of patients' pain. Contrary to
      predictions, patient-physician agreement was not related to better patient well
      being. Agreement between patients and physicians was associated with less (rather
      than more) self-efficacy and positive affect when compared to physicians'
      underestimation of patients' pain.

PMID- 14581108
TI  - Development of a metric for a day of manageable pain control: derivation of pain
      severity cut-points for low back pain and osteoarthritis.
AB  - The objective of this study was to adapt the concept of 'episode-free day', a
      metric for measuring symptom relief in daily units, to the clinical outcome
      literature for persistent pain. The episode-free day metric is widely used in
      other medical literature, but no analogous measure exists in pain literature.
      Prior focus groups with this population suggested that a 'Day of Manageable Pain
      Control' was an appropriate name for the metric. In the present study, in order
      to derive a statistical criterion for 'Manageable Day', we used Serlin et al.'s
      (Pain 61 (1995) 277) cut-point derivation method to derive a single cut-point on
      a 0-10 scale of average pain that divided groups with significant persistent pain
      optimally on pain-related functional interference. Participants were 194 patients
      with moderate-severe low back pain (n=96) or osteoarthritis (n=98). For both
      patient samples, '5' was the cut-point that optimally distinguished groups on
      pain-related interference. '5-8' and '5-7' were double cut-point solutions that
      optimally divided LBP and OA samples into three categories (e.g. lowest, medium
      and highest average pain), respectively. Derived cut-points were confirmed using
      a variety of measures of functional disability. Together with research that
      showed that average pain ratings of approximately 5 and below permit increased
      function and quality of life in patients with moderate to severe low back pain
      and osteoarthritis, our findings provide support for the use of 0-5 on a 0-10
      numeric average pain severity scale as one possible criterion for a Manageable
      Day.

PMID- 14581109
TI  - Altered dopamine D2 receptor binding in atypical facial pain.
AB  - Animal studies suggest that the dopaminergic system plays a role in central pain
      modulation. We have previously demonstrated with positron emission tomography
      (PET) that striatal dopaminergic hypofunction may be involved in the burning
      mouth syndrome. The aim of the present study was to evaluate the nigrostriatal
      dopaminergic system in patients with atypical facial pain using PET. In seven
      patients with atypical facial pain, striatal presynaptic dopaminergic function
      was assessed with [18F]FDOPA and dopamine D1 and D2 receptor availabilities with
      [11C]NNC 756 and [11C]raclopride, respectively. The results were compared with
      those of healthy controls. A quantitative region-of-interest analysis showed that
      the uptakes of [18F]FDOPA and [11C]NNC 756 did not differ between patients and
      controls. There was a tendency of increased D2 receptor availability in the left
      putamen (P=0.056), and the D1/D2 ratio in the putamen was decreased bilaterally
      by 7.7% (P=0.002) in patients when compared to controls. In a voxel-based
      analysis, the uptake of [11C]raclopride was increased in the left putamen
      (P=0.025). In conclusion, the increase in D2 receptor availability in the left
      putamen and the decrease in D1/D2 ratio imply that alterations in the striatal
      dopaminergic system as evaluated by PET may be involved in chronic orofacial pain
      conditions.

PMID- 14581110
TI  - Short-term infusion of the mu-opioid agonist remifentanil in humans causes
      hyperalgesia during withdrawal.
AB  - Numerous animal studies suggest that acute and chronic exposure to opioids can be
      associated with the development of hyperalgesia, i.e. an increased sensitivity to
      noxious stimuli. Hyperalgesia has been documented during withdrawal and on
      occasion while animals were still exposed to opioids. A pivotal role in the
      genesis of opioid-associated hyperalgesia has been attributed to a pain
      facilitating system involving the N-methyl-D-aspartate (NMDA)-receptor. In humans
      little direct evidence documents opioid-associated hyperalgesia, albeit
      observational data suggest that such hyperalgesia may be relevant in a clinical
      context. This study used a double blind, randomized, crossover and placebo
      controlled design to test in opioid-naive, healthy human volunteers whether
      hyperalgesia would develop within 30 min of stopping a 90-min infusion with the
      mu-opioid agonist remifentanil, and whether co-administration of the NMDA
      receptor antagonist S-ketamine would prevent such hyperalgesia. We found that a
      skin area with pre-existing mechanical hyperalgesia was significantly enlarged
      after stopping the remifentanil infusion. However, the pain response to heat
      assessed in regular skin was not different before and after the infusion of
      remifentanil. Co-administration of the NMDA-receptor antagonist S-ketamine
      abolished observed enlargement of the hyperalgesic skin area. This study provides
      direct evidence in humans that short-term administration of an opioid can enhance
      hyperalgesia as observed during withdrawal and points to a potential role of the
      NMDA-receptor system in mediating such a hyperalgesic response. This study also
      points to a differential susceptibility of different pain modalities for the
      expression of hyperalgesia associated with opioid administration.

PMID- 14581111
TI  - Topical treatment of chronic low back pain with a capsicum plaster.
AB  - The efficacy and tolerance of a capsicum plaster in non-specific low back pain
      was investigated in a double-blind, randomised, placebo-controlled multicentre
      parallel group study. A total of 320 patients were randomly assigned to two
      groups of n=160 subjects treated by the active or the placebo plaster. The main
      outcome measures used were a compound pain subscore of the Arhus low back rating
      scale (continuous variable), and a response criterion of a reduction in pain
      subscore=30% from baseline to final assessment (secondary, non-continuous
      variable). In addition, the partial pain scores, disability and mobility
      restriction subscores, the total score of the Arhus low back rating scale, the
      global evaluation of efficacy by investigator and patient, adverse events, a
      patient questionnaire on use of the plaster, and an evaluation of tolerance by
      investigator and patient were obtained. After 3 weeks treatment with capsicum and
      placebo plaster respectively, the compound pain subscore was reduced by 42%
      (capsicum) and 31% (placebo) from values on entry. Responder rate was 67% versus
      49% (p=0.002). The investigators rated efficacy as "excellent" or "good" by 74%
      and 36%; the patient's efficacy rating "symptomfree" or "improved" reached 82%
      and 50%. Adverse local drug reactions were found in 12 patients (7.5%) on
      capsicum and 5 (3.1%) on placebo. No systemic side-effects were observed. The
      superiority of the treatment of chronic non-specific low back pain with capsicum
      plaster compared to placebo was clinically relevant and highly statistically
      significant. The capsicum plaster offers a genuine alternative in the treatment
      of non-specific low back pain.

PMID- 14581112
TI  - Acceptance of pain is an independent predictor of mental well-being in patients
      with chronic pain: empirical evidence and reappraisal.
AB  - This paper reports upon: (1) the value of acceptance of pain in predicting well
      being in patients suffering from chronic pain and (2) the construct validity of
      acceptance by comparing two questionnaires designed to measure acceptance (the
      Chronic Pain Acceptance Questionnaire, CPAQ, unpublished doctoral dissertation,
      University of Nevada, Reno, NV, 1992 and the Illness Cognitions Questionnaire,
      ICQ, J Consult Clin Psychol 69 (2001) 1026). The results of two independent cross
      sectional studies are reported. Study 1 included 120 patients seeking help in
      tertiary care settings. In Study 2, 66 patients were recruited from a self
      support group for fibromyalgia patients and from a pain clinic. Both studies
      revealed that acceptance of pain predicted mental well-being beyond pain severity
      and pain catastrophizing, but did not account for physical functioning. In both
      instruments, it was found that acceptance of pain was strongly related to
      engagement in normal life activities and the recognition that pain may not
      change. Acceptance in both instruments was strongly related to a cognitive
      control over pain. Study 2 further revealed that the correlation between the CPAQ
      and the ICQ is moderate, indicating that both instruments measured different
      aspects of acceptance. It is concluded that acceptance of chronic pain is best
      conceived of as the shift away from pain to non-pain aspects of life, and the
      shift away from a search for a cure with an acknowledgement that pain may not
      change.

PMID- 14581113
TI  - Effects of TENS frequency, intensity and stimulation site parameter manipulation
      on pressure pain thresholds in healthy human subjects.
AB  - This study evaluated the effects of varying frequency, intensity and stimulation
      site, of transcutaneous electrical nerve stimulation (TENS) in an experimental
      model of pain. In a double-blind design 240 volunteers were randomised to one of
      six experimental TENS groups, a sham TENS or control (n=30 per group; gender
      balanced). Two TENS frequencies (110 or 4 Hz) and two intensities (strong but
      comfortable or highest tolerable) at a fixed pulse duration (200 micros) were
      applied at three sites relative to the measurement site (segmentally,
      extrasegmentally or a combination of these), for 30 min. Pressure pain thresholds
      (PPT) were measured using a pressure algometer, in the first dorsal interosseous
      muscle, every 10 min, during stimulation and for a further 30 min. The high
      frequency, high intensity segmental, and combined stimulation groups, showed
      rapid onset and significant hypoalgesic effects. This effect was sustained for 20
      min post-stimulation in the high frequency segmental group. All other TENS
      intervention groups showed hypoalgesic responses similar to the sham TENS group,
      and none of these groups reached a clinically significant hypoalgesic level.
      CONCLUSIONS: The role of TENS frequency, intensity and site are pivotal to
      achieving optimal hypoalgesic effects, during and after stimulation. Clinical
      applications of these parameter combinations require further investigations.

PMID- 14581114
TI  - Factors associated with the onset and remission of chronic daily headache in a
      population-based study.
AB  - The etiology and prognosis of chronic daily headache (CDH) are not well
      understood. The aim of this study is to describe factors that predict CDH onset
      or remission in an adult population. Potential cases (180+ headaches per year,
      n=1134) and controls (two to 104 headaches per year, n=798) were interviewed two
      times over an average 11 months of follow-up. Factors associated with CDH
      prevalence at baseline were evaluated. The incidence of CDH and risk factors for
      onset were assessed in controls whose headache frequency increased to 180+ per
      year at follow-up. Prognostic factors were assessed in CDH cases whose headache
      frequency fell at follow-up. CDH was more common in women, in whites, and those
      of less education. CDH cases were more likely to be previously married (divorced,
      widowed, separated), obese, and report a physician diagnosis of diabetes or
      arthritis. At follow-up, 3% of the controls reported 180 or more headaches per
      year. Obesity and baseline headache frequency were significantly associated with
      new onset CDH. In CDH cases, the projected 1-year remission rate to less than one
      headache per week was 14% and to less than 180 headaches per year was 57%. A
      better prognosis was associated with higher education, non-white race, being
      married, and with diagnosed diabetes. Individuals with less than a high-school
      education, whites, and those who were previously married had a higher risk of CDH
      at baseline and reduced likelihood of remission at follow-up. New onset CDH was
      associated with baseline headache frequency and obesity.

PMID- 14581116
TI  - Effects of odors on pain perception: deciphering the roles of emotion and
      attention.
AB  - Emotions have been shown to alter pain perception, but the underlying mechanism
      is unclear since emotions also affect attention, which itself changes nociceptive
      transmission. We manipulated independently direction of attention and emotional
      state, using tasks involving heat pain and pleasant and unpleasant odors. Shifts
      in attention between the thermal and olfactory modalities did not alter mood or
      anxiety. Yet, when subjects focused attention on the pain, they perceived it as
      clearly more intense and somewhat more unpleasant than when they attended to the
      odor. In contrast, odor valence altered mood, anxiety level, and pain
      unpleasantness, but did not change the perception of pain intensity. Pain
      unpleasantness ratings correlated with mood, but not with odor valence,
      suggesting that emotional changes underlie the selective modulation of pain
      affect. These results show that emotion and attention differentially alter pain
      perception and thus invoke at least partially separable neural modulatory
      circuits.

PMID- 14581117
TI  - Emotion induction moderates effects of anger management style on acute pain
      sensitivity.
AB  - Anger management style (AMS) is related to both acute and chronic pain intensity.
      Recent work suggests that an anger expressive AMS in particular may influence
      acute pain, and that this effect may be most pronounced during anger provocation.
      The present study examined whether AMS was related to subsequent pain sensitivity
      without regard to prior emotion induction, only when a strong negative emotion
      was evoked, or only when anger was provoked. Sixty-four healthy normals partook
      in semi-structured interviews in which they recalled and verbally described an
      event in which either anger, sadness, or joy was elicited. They then underwent a
      cold pressor pain task. Results of hierarchical multiple regressions showed that
      an anger expressive AMS was related positively to pain threshold only for
      participants in the anger-recall condition, and that this effect was largely
      accounted for by their low SBP reactivity during emotion induction. An anger
      suppressive AMS was related positively to increases in self-reported pain
      severity, irrespective of emotion-induction condition, and this effect was not
      accounted for by reactivity in any cardiovascular index. Results extend those of
      previous studies by illuminating the potential importance of behavioral anger
      expression for individuals prone to express anger in modulating their reactivity
      and pain sensitivity. Findings suggest that the detrimental effects of an anger
      expressive style on pain sensitivity may be ameliorated under conditions in which
      behavioral anger expression occurs. Results are discussed in terms of recent work
      suggesting that an expressive AMS is associated with endogenous opioid
      dysfunction in the absence of behavioral anger expression.

PMID- 14581115
TI  - Naloxone provokes similar pain facilitation as observed after short-term infusion
      of remifentanil in humans.
AB  - In contrast to an expected preventive analgesic effect, clinical observations
      suggest that intraoperatively applied opioids can induce postoperative
      hyperalgesia. We tested the development of post-infusion hyperalgesia in a newly
      developed experimental model of electrically induced pain and secondary
      mechanical hyperalgesia. In a double-blind, placebo controlled, cross-over study,
      13 subjects received either saline placebo, remifentanil (0.05 or 0.1
      microg/kg/min) or naloxone (0.01 mg/kg). Remifentanil dose-dependently reduced
      pain and mechanical hyperalgesia during the infusion, but upon withdrawal, pain
      and hyperalgesia increased significantly above control level (p<0.01 and p<0.05,
      respectively). Naloxone infusion similarly resulted in increased pain (anti
      analgesia) (p<0.001) and mechanical hyperalgesia (p<0.01). Increased pain ratings
      following withdrawal of remifentanil significantly correlated to anti-analgesia
      evoked by the mu-opioid antagonist naloxone (p<0.01) and was of similar
      magnitude, suggesting inhibition of endogenous opioids as an underlying
      mechanism. In contrast, hyperalgesia after remifentanil was more pronounced than
      hyperalgesia after naloxone administration and did not correlate to the observed
      anti-analgesic effects, suggesting the involvement of additional receptors
      systems other than the endorphin system.

PMID- 14581118
TI  - The effect of opioid analgesia on exercise test performance in chronic low back
      pain.
AB  - The effect of opioid analgesia on tests of muscular function in chronic low back
      pain (CLBP) is unknown. Twenty-eight subjects with CLBP of at least moderate
      intensity performed the Sorensen isokinetic exercise test once after receiving 1
      microg/kg fentanyl intravenously and once after placebo in a randomized-order
      double-blind crossover design. Naloxone 3 microg/kg was administered after the
      fentanyl phase. Fentanyl reduced mean+/-SD pain from 4.0+/-2.1 to 3.1+/-2.2 on a
      0-10 verbal rating scale (P<0.05). Mean+/-SD Sorensen test performance was 77+/
      49 s in the fentanyl arm and 60+/-42 s in the placebo arm. This represents an
      increased performance with fentanyl of 28% (P<0.001). We conclude that in
      addition to relieving pain in CLBP, the administration of 1 microg/kg fentanyl is
      associated with an improvement in lumbar exercise test performance. We presume
      that the pain relief resulted in increased test performance. Our result is at
      odds with those of randomized trials which have failed to demonstrate increased
      function following the treatment of pain with opioid analgesics. This highlights
      the complexity of the interaction between pain, analgesia and changes in
      function.

PMID- 14581119
TI  - Mood and anxiety disorders associated with chronic pain: an examination in a
      nationally representative sample.
AB  - Chronic pain and psychiatric disorders frequently co-occur. However, estimates of
      the magnitude of these associations have been biased by the use of select
      clinical samples. The present study utilized the National Comorbidity Survey
      [Arch. Gen. Psychiatry 51 (1994) 8-19] Part II data set to investigate the
      associations between a chronic pain condition (i.e. arthritis) and common mood
      and anxiety disorders in a sample representative of the general US civilian
      population. Participants (N=5877) completed the Composite International
      Diagnostic Interview [World Health Organization (1990)], a structured interview
      for trained non-clinician interviewers based on the revised third edition of the
      Diagnostic and Statistical Manual of Mental Disorders [American Psychiatric
      Association (1987)], and provided self-reports of pain and disability associated
      with a variety of medical conditions. Significant positive associations were
      found between chronic pain and individual 12-month mood and anxiety disorders
      [odds ratios (OR) ranged from 1.92 to 4.27]. The strongest associations were
      observed with panic disorder (OR=4.27) and post-traumatic stress disorder
      (OR=3.69). The presence of one psychiatric disorder was not significantly
      associated with pain-related disability, but the presence of multiple psychiatric
      disorders was significantly associated with increased disability. The findings of
      the present study raise the possibility that improved efforts regarding the
      detection and treatment of anxiety disorders may be required in pain treatment
      settings.

PMID- 14581120
TI  - 5-hydroxytryptamine1A receptor is involved in the bee venom induced inflammatory
      pain.
AB  - Injection of bee venom into one hindpaw of rat can elicit acute inflammation
      together with spontaneous pain, heat hyperalgesia and mechanical
      hyperalgesia/allodynia in the injected paw. 5-hydroxytryptamine (5-HT)1A receptor
      is the predominant receptor subtype in the spinal dorsal horn mediating the
      function of 5-HT in nociception. The goal of the present study is to assess the
      role of 5-HT1A receptor in the pain associated with the bee venom induced
      inflammation. Here we showed that 1 or 4 h after a subcutaneous bee venom
      challenge, expression of 5-HT1A receptor mRNA in the ipsilateral lumbar spinal
      cord increased significantly by 80.94 or 37.86%, respectively. Antisense
      oligodeoxynucleotide knockdown of spinal 5-HT1A receptor attenuated spontaneous
      pain and reversed heat hyperalgesia in rats injected with bee venom. Thus, the
      present data suggest a facilitating role for 5-HT1A receptor in bee venom induced
      inflammatory pain.

PMID- 14581121
TI  - An antinociceptive role of galanin in the arcuate nucleus of hypothalamus in
      intact rats and rats with inflammation.
AB  - In the arcuate nucleus of hypothalamus (ARC), galaninergic fibers form synaptic
      contacts with proopiomelanocortin neurons, which are involved in pain modulation.
      The present study assessed the role of exogenous and endogenous galanin in the
      modulation of nociception in the ARC of rats. The hindpaw withdrawal latency
      (HWL) to thermal and mechanical stimulation was assessed by the hot-plate test
      and the Randall Selitto Test. Intra-ARC injection of galanin dose-dependently
      increased the HWLs in intact rats, indicating an antinociceptive role of
      exogenous galanin in the ARC. The antinociceptive effect of galanin was blocked
      by following intra-ARC injection of galantide, a putative galanin receptor
      antagonist, suggesting that the antinociceptive effect of galanin is mediated by
      galanin receptors. Moreover, intra-ARC injection of galanin increased the HWL in
      rats with inflammation. Intra-ARC administration of galantide alone reduced the
      HWLs in rats with inflammation, while there were no influences of galantide on
      the HWL in intact rats. Taken together, the results show that galanin has an
      antinociceptive role in the ARC of intact rats and rats with inflammation.

PMID- 14581122
TI  - Efficacy of lidocaine patch 5% in the treatment of focal peripheral neuropathic
      pain syndromes: a randomized, double-blind, placebo-controlled study.
AB  - Peripheral neuropathic pain syndromes (PNPS) are difficult to treat because
      commonly used analgesics are often ineffective when, for example, touch-evoked
      allodynia, hyperalgesia, and pain paroxysms are present. To investigate whether
      lidocaine patch 5% treatment is also effective in postherpetic neuropathy (PHN)
      and in other PNPS, 40 patients with various forms and localizations of PNPS
      completed a prospective, randomized, placebo-controlled, two-way, cross-over
      study in three medical hospitals. Patients suffering from pain in a localized
      skin area with intensity above 40 mm visual analog scale (VAS) and a stable
      consumption of pain medication were included in this study. The study was divided
      into four phases: 3-day run-in phase, treatment phase 1, wash-out period, and
      treatment phase 2, each lasting 1 week. At the discretion of the patients, up to
      four patches (covering a maximum of 560 cm2) were applied onto the maximally
      painful area for 12 consecutive hours daily, always either by day or at night.
      Throughout the four phases, ongoing pain, allodynia, quality of neuropathic
      symptoms, quality of sleep, and adverse events were assessed. When, after the
      wash-out period, the pain intensity scores did not return to the pre-treatment
      values (+/-20%), these patients were excluded from the study. The present study
      revealed that, as an add-on therapy, the lidocaine patch 5% was clearly effective
      in reducing ongoing pain (P=0.017) and allodynia (P=0.023) during the first 8 h
      after application and that the patches also worked well over a period of 7 days
      (P=0.018) in diverse focal PNPS. Calculation of the numbers needed to treat (NNT)
      to obtain one patient with more than 50% relief of ongoing pain revealed that the
      NNT of 4.4 in the present study compared reasonably well with other studies of
      PHN, such as topically applied capsaicin (NNT: 5.3-infinity) or systemic
      treatment with gabapentin (NNT: 3.2-5.0).

PMID- 14581124
TI  - Lack of analgesic efficacy of oral delta-9-tetrahydrocannabinol in postoperative
      pain.
AB  - We have evaluated the efficacy of delta-9-tetrahydrocannabinol (delta-9-THC), the
      main psychoactive constituent of cannabis, in postoperative pain. In a randomized
      double-blind, placebo-controlled, single-dose trial, we investigated 40 women
      undergoing elective abdominal hysterectomy. Randomization took place when
      postoperative patient-controlled analgesia was discontinued on the second
      postoperative day. When patients requested further analgesia, they received a
      single, identical capsule of either oral delta-9-THC 5 mg (n=20) or placebo
      (n=20) in a double-blind fashion. The primary outcome measure was summed pain
      intensity difference (SPID) at 6 h after administration of study medication
      derived from visual analogue pain scores on movement and at rest. Secondary
      outcome measures were time to rescue medication and adverse effects of study
      medication. Mean (SD) VAS pain scores before medication in the placebo and delta
      9-THC groups were 6.3(2.6) and 6.4(1.3)cm on movement, and 3.2(1.9) and 3.3(0.9)
      on rest, respectively. There were no significant differences in mean (95%
      confidence interval of the difference) SPID at 6 h between the groups [placebo
      7.9, delta-9-THC 4.3(-1.8 to 9.0)cm h on movement; placebo 8.8, delta-9-THC 4.9(
      0.2 to 8.1)cm h at rest] and time to rescue analgesia [placebo 217, delta-9-THC
      163(-22 to 130)min]. Increased awareness of surroundings was reported more
      frequently in patients receiving delta-9-THC (40 vs 5%, P=0.04). There were no
      other significant differences with respect to adverse events. This study
      demonstrates no evidence of an analgesic effect of orally administered delta-9
      THC 5 mg in postoperative pain in humans.

PMID- 14581125
TI  - Contribution of spinal glutamatergic mechanisms in heterosegmental
      antinociception induced by noxious stimulation.
AB  - We evaluated the role of spinal glutamate and substance P receptors in noxious
      stimulus-induced antinociception (NSIA). NSIA was produced by subdermal capsaicin
      administration in the hind paw of the rat and measured as attenuation of the jaw
      opening reflex. NSIA was completely blocked by spinal intrathecal administration
      of the selective NMDA receptor antagonist LY235959 as well as the mGluR5
      antagonists MPEP and SIB-1757 and partially attenuated by the selective
      AMPA/kainate receptor antagonist NBQX; however, neither the mGluR1 receptor
      antagonist LY367385 nor the NK1 antagonist L-703,606 affected NSIA. These results
      suggest that NSIA depends on glutamate, released from the central terminals of
      the primary afferent nociceptors, acting primarily on NMDA and mGluR5 receptors.
      Although substance P is also known to be released by similar stimuli, NK1
      receptors do not appear to play a role in NSIA. The implications of these
      findings in the context of a proposed spinal circuit that mediates NSIA are
      discussed.

PMID- 14581123
TI  - Joint manipulation reduces hyperalgesia by activation of monoamine receptors but
      not opioid or GABA receptors in the spinal cord.
AB  - Joint manipulation has long been used for pain relief. However, the underlying
      mechanisms for manipulation-related pain relief remain largely unexplored. The
      purpose of the current study was to determine which spinal neurotransmitter
      receptors mediate manipulation-induced antihyperalgesia. Rats were injected with
      capsaicin (50 microl, 0.2%) into one ankle joint and mechanical withdrawal
      threshold measured before and after injection. The mechanical withdrawal
      threshold decreases 2 h after capsaicin injection. Two hours after capsaicin
      injection, the following drugs were administered intrathecally: bicuculline,
      blocks gamma-aminobutyric acid (GABAA) receptors; naloxone, blocks opioid
      receptors; yohimbine blocks, alpha2-adrenergic receptors; and methysergide,
      blocks 5-HT(1/2) receptors. In addition, NAN-190, ketanserin, and MDL-72222 were
      administered to selectively block 5-HT1A, 5-HT2A, and 5-HT3 receptors,
      respectively. Knee joint manipulation was performed 15 min after administration
      of drug. The knee joint was flexed and extended to end range of extension while
      the tibia was simultaneously translated in an anterior to posterior direction.
      The treatment group received three applications of manipulation, each 3 min in
      duration separated by 1 min of rest. Knee joint manipulation after capsaicin
      injection into the ankle joint significantly increases the mechanical withdrawal
      threshold for 45 min after treatment. Spinal blockade of 5-HT(1/2) receptors with
      methysergide prevented, while blockade of alpha2-adrenergic receptors attenuated,
      the manipulation-induced antihyperalgesia. NAN-190 also blocked manipulation
      induced antihyperalgesia suggesting that effects of methysergide are mediated by
      5-HT1A receptor blockade. However, spinal blockade of opioid or GABAA receptors
      had no effect on manipulation induced-antihyperalgesia. Thus, the
      antihyperalgesia produced by joint manipulation appears to involve descending
      inhibitory mechanisms that utilize serotonin and noradrenaline.

PMID- 14581126
TI  - Sweet taste and blood pressure-related analgesia.
AB  - To test the prediction that sweet taste modifies responses to cold induced pain,
      72 young adults held sweet, bitter and water solutions in their mouths, in
      counterbalanced order, before and during a cold pain stimulus. To test whether or
      not blood pressure interacts with sweet taste analgesia, measurements of resting
      blood pressure were also obtained. A significant main effect of taste on pain
      tolerance was observed, as well as a significant interaction between resting mean
      arterial pressure (MAP) and taste on tolerance. Sweet taste was associated with a
      prolongation of tolerance compared to the bitter and water conditions. When
      participants were split along the median for MAP, sweet taste was associated with
      an 18.1% increase in pain tolerance compared with water for those with lower MAP.
      No significant impact of taste on pain sensitivity was observed among
      participants with higher MAP. Groupwise comparisons revealed a significant
      difference in pain tolerance between participants with higher and lower MAP in
      the water condition but not in the sweet condition, replicating previous findings
      of a reduced sensitivity to pain among those with higher blood pressure. The
      analgesic effects of sweet tasting solutions seen previously in human infants and
      children may also be present in adults. Individuals with higher blood pressure
      may not be as sensitive to the presumably opioid-mediated analgesic effects of
      sweet taste, perhaps due to opioid dysregulation.

PMID- 14581127
TI  - Effect of knock down of spinal cord PSD-93/chapsin-110 on persistent pain induced
      by complete Freund's adjuvant and peripheral nerve injury.
AB  - PSD-93/chapsin-110 is a neuronal PDZ domain-containing protein that binds to and
      clusters the N-methyl-D-aspartate receptor (NMDAR) at synapses in the central
      nervous system. It also assembles a specific set of signaling proteins around the
      NMDAR and mediates downstream signaling by the NMDAR. Thus, PSD-93/chapsin-110
      might be involved in many physiological and pathophysiological actions triggered
      via the activation of the NMDAR. In the current study, we report that abundant
      PSD-93/chapsin-110 protein was detected in rat spinal cord, particularly in the
      superficial dorsal horn. The rats injected intrathecally with PSD-93/chapsin-110
      antisense oligodeoxynucleotide every 24 h for 4 days displayed not only a
      remarkable decrease in spinal cord PSD-93/chapsin-110 expression but also a
      significant reduction in the paw withdrawal responses to thermal and mechanical
      stimuli during complete Freund's adjuvant-induced inflammatory pain and
      peripheral nerve injury-induced neuropathic pain. In contrast, the rats injected
      intrathecally with PSD-93/chapsin-110 missense oligodeoxynucleotide did not
      exhibit these changes. We also found that pretreatment with PSD-93/chapsin-110
      antisense oligodeoxynucleotide did not change the locomotor activity or the
      responses to acute noxious thermal and mechanical stimuli in intact rats. The
      present results indicate that the deficiency of spinal cord PSD-93/chapsin-110
      protein significantly attenuates thermal and mechanical hyperalgesia in complete
      Freund's adjuvant- or peripheral nerve injury-induced chronic pain. This suggests
      that spinal cord PSD-93/chapsin-110 might be involved in the central mechanism of
      chronic pain. Our work might provide a new target for the therapy of chronic
      pain.

PMID- 14581129
TI  - Questions concerning the incidence and prevalence of complex regional pain
      syndrome type I (RSD).

PMID- 14581128
TI  - Effects of corticotropin-releasing factor on plasticity of optically recorded
      neuronal activity in the substantia gelatinosa of rat spinal cord slices.
AB  - We examined the effects of corticotropin-releasing factor (CRF) on plasticity of
      optically recorded neuronal activity in the substantia gelatinosa (lamina II) of
      12-18-day-old rat spinal cord slices stained with a voltage-sensitive dye. Single
      pulse test stimulation to the dorsal root that activated A and C fibres evoked
      prolonged (>100 ms) light-absorption change in the lamina II. This response
      represents the gross membrane potential change of all elements along the slice
      depth. After conditioning high-frequency stimulation of A-fibre-activating
      strength, test stimulus elicited less neuronal activity [-27+/-1% (7), (average+/
      SE (n)), P<0.01 (*) at 45-60 min after conditioning]. When CRF (1 microM, 10 min)
      was applied during conditioning, the neuronal activity was facilitated rather
      than suppressed [+20+/-3% (5), P<0.05]. CRF alone exhibited insignificant effect
      [-5+/-1% (4), P=0.2]. In the presence of the inhibitory amino acid antagonists
      bicuculline (1 microM) and strychnine (0.3 microM) in the perfusate, in contrast,
      the conditioning facilitated it [+27+/-1% (12)*], and CRF treatment during
      conditioning inhibited the facilitation dose-dependently [0.1 microM: +18+/-2%
      (5)*, 1 microM: +13+/-1% (7)*]. Although interneuronal actions might contribute,
      these results suggest that CRF may have dual effects on excitatory synaptic
      transmission within the lamina II depending upon cellular conditions: a
      conversion from the induction of long-term depression to long-term potentiation
      (LTP), and inhibition of LTP induction. Since the LTP is thought to be
      responsible at least in part for the persistent pain, CRF could regulate the
      induction.

PMID- 14581133
TI  - Photosensitivity in cutaneous lupus erythematosus: lessons from mice and men.
AB  - Mouse models are similar but not identical to human diseases. However, they are
      important for research into the pathogenesis underlying autoimmune diseases
      because they allow us to evaluate similarities and differences between human
      diseases and mouse models. In fact, experimental models and inbred lupus-prone
      mice are tools that enable a better understanding of the 'photosensitivity' or
      'photocytotoxicity' phenomena in relation to autoimmunity. Genetic studies of
      MRL/lpr mice revealed that the appearance of macroscopic lupus erythematosus (LE)
      like skin lesions needs the lpr mutation plus an additional factor in an
      autosomal dominant fashion. The candidate is ultraviolet (UV) B light, the
      susceptibility to which is regulated by the genetic background. Such a genetic
      background is also speculated to be important in human cutaneous LE patients. The
      translocation of anti-SS-A/Ro on cultured keratinocytes irradiated with UVB light
      is quantitatively different from photocytotoxicity, and the quantitative levels
      are significantly higher in systemic LE and subacute cutaneous LE than in discoid
      LE and normal controls. This review focuses on the lessons gleaned from mouse and
      human models, and discusses photosensitivity in human cutaneous LE.

PMID- 14581134
TI  - Involvement of hyaluronan in epidermal Langerhans cell maturation and migration
      in vivo.
AB  - BACKGROUND: Langerhans cells (LC) normally reside in the epidermis, where they
      constantly monitor the integrity of this microenvironment. Skin exposure to
      reactive haptens or other pro-inflammatory stimuli triggers LC migration to the
      draining lymph nodes, where they function as potent antigen presenting cells. At
      the same time, migratory LC exhibit features of mature dendritic cells.
      OBJECTIVE: The purpose of this study was to determine the potential role(s) of
      hyaluronan (HA) in the process of LC maturation. METHODS: Using a recently
      described inhibitor of HA, termed 'Pep-1', we assessed the kinetics of LC
      migration and maturation in mice. Migration was determined by assessing LC
      density in epidermal sheets after hapten application. Epidermal LC maturation was
      evaluated by cell morphology, surface expression of CD86 and allogeneic mixed
      lymphocyte reactions. RESULTS: Local injections of Pep-1 prevented LC migration
      from hapten-painted skin almost completely in the first 24 h. On the other hand,
      LC began to emigrate from the epidermis at 48 h, indicating that Pep-1 simply
      delayed LC migration by approximately 24 h. Locally injected Pep-1 inhibited
      hapten-induced LC maturation at 24 h as assessed by morphological changes, CD86
      expression levels, and T cell-stimulatory potentials. Strikingly, all
      maturational changes became detectable at 48 h. CONCLUSION: Pep-1 inhibits LC
      migration and maturation with the same kinetics, presumably reflecting close
      association of the two events. Moreover, our results suggest dual functionality
      of HA to facilitate LC migration and maturation, the two critical events for the
      initiation of adaptive immune responses in the skin.

PMID- 14581135
TI  - Fast omega-gliadin is a major allergen in wheat-dependent exercise-induced
      anaphylaxis.
AB  - BACKGROUND: Wheat-dependent exercise-induced anaphylaxis is an anaphylaxy induced
      by physical exercise after ingestion of wheat. An immediate-type hypersensitivity
      to water/salt-insoluble fraction of wheat proteins (gluten) has been considered
      to underlie in this disease. OBJECTIVE: The aim of the study is to determine the
      major allergen in Japanese patients with wheat-dependent exercise-induced
      anaphylaxis by using a panel of purified wheat gliadins and glutenins. METHODS:
      Water/salt-insoluble wheat proteins, alpha-gliadin, beta-gliadin, gamma-gliadin,
      fast omega-gliadin, slow omega-gliadin, high molecular weight glutenin and low
      molecular weight glutenin, were purified, and five patients with wheat-dependent
      exercise-induced anaphylaxis, whose diagnose had been determined by positive
      challenge test, were evaluated for skin prick test, dot-blotting test and CAP
      RAST inhibition test by using these purified wheat proteins. RESULTS: The fast
      omega-gliadin was the most potent allergen among these water/salt-insoluble
      proteins when evaluated by skin prick test and dot-blotting test. Fast and slow
      omega-gliadin, and gamma-gliadin caused dose-dependent inhibition of the serum
      IgE-binding to solid-phase gluten in the patients. The incubation with fast omega
      gliadin of the patient's serum caused dose-dependent inhibition in the IgE
      binding to gamma-gliadin as well as slow omega-gliadin, indicating a cross
      reactivity of these proteins in IgE-binding. CONCLUSION: We concluded that fast
      omega-gliadin is a major allergen among these water/salt-insoluble proteins for
      wheat-dependent exercise-induced anaphylaxis in Japanese patients, and IgE
      against fast omega-gliadin cross-reacts to gamma-gliadin and slow omega-gliadin.

PMID- 14581136
TI  - Induction of matrix metalloproteinase-9 secretion from human keratinocytes in
      culture by ultraviolet B irradiation.
AB  - BACKGROUND: Matrix metalloproteinases (MMPs) are known as important enzymes
      involved in tissue metabolism. Among them, MMP-2 and MMP-9 are termed
      gelatinases, but their specific roles in vivo are still unknown, including their
      expression patterns following ultraviolet (UV) irradiation. OBJECTIVE: To
      elucidate the effects of UV irradiation on the skin, we analyzed the expression
      of MMP-2 and MMP-9 by primary human keratinocytes in culture. METHODS: We
      evaluated the enzymatic functions of MMP-2 and MMP-9 by gelatin-zymography, and
      of MMP-9 expression by immunofluorescence, using cultured keratinocytes after UV
      irradiation. RESULTS: The secretion of MMP-2 (72 kDa) remained at low levels
      under all conditions examined. Although MMP-9 (92 kDa) secretion was not induced
      by UVA, it was stimulated by UVB irradiation in a dose-dependent manner. In
      addition, an enzyme-linked immunosorbent assay showed the tendency to increase
      for the involucrin expression following UVB exposure. Cell viability was
      decreased by UVB irradiation in contrast to the induction of MMP-9 and
      involucrin. CONCLUSION: These results suggest that the induction of MMP-9
      secretion is related to the inflammation including apoptosis of keratinocytes
      resulting from UVB irradiation.

PMID- 14581137
TI  - Usefulness of immunoblotting using purified laminin 5 in the diagnosis of anti
      laminin 5 cicatricial pemphigoid.
AB  - BACKGROUND: Anti-laminin 5 cicatricial pemphigoid (CP) is a mucosal-dominant
      subepithelial blistering disease characterized by IgG anti-basement membrane zone
      autoantibodies, that bind to dermal side of 1 M NaCl split skin and
      immunoprecipitate laminin 5. Laminin 5 is an epidermis-specific extracellular
      matrix consisting of alpha3, beta3 and gamma2 subunits. Recent studies have
      suggested that autoantibodies of anti-laminin 5 CP recognize the G domains of
      alpha3 subunit. OBJECTIVE: We examined the reactivity of anti-laminin 5 CP by
      immunoblotting using purified laminin 5 and recombinant proteins of alpha3
      subunit. METHOD: We first examined the reactivity of anti-laminin 5 CP by
      immunoblotting using purified laminin 5. To further investigate the epitopes in
      the G domains of alpha3 subunit, we produced recombinant proteins of G1-2, G1-3,
      G2-3, G3-5 domains, that covered entire G domain, and examined the reactivity of
      anti-laminin 5 CP sera with these recombinant proteins by immunoblotting.
      RESULTS: By immunoblotting using purified laminin 5, 7 of 21 anti-laminin 5 CP
      sera reacted with alpha3 subunit, while 8 sera reacted with beta3 subunit and one
      serum reacted with gamma2 subunit. Two sera reacted with both alpha3 and beta3
      subunits, while seven sera did not show positive reactivity. This result
      indicates that the reactivity of anti-laminin 5 CP sera is much more
      heterogeneous, although the previous studies suggested that most sera reacted
      with alpha3 subunit. However, in the studies using recombinant proteins of G
      domains of alpha3 subunit, none of the CP sera, including the sera reactive with
      alpha3 subunit in purified laminin 5, reacted with any recombinant proteins. The
      reason for this negative reactivity with the recombinant proteins is not clear.
      CONCLUSION: The immunoblotting using purified laminin 5 should be useful
      technique for the diagnosis of anti-laminin 5 CP, although the sensitivity was
      less than conventional immunoprecipitation analysis.

PMID- 14581138
TI  - Heterogeneity of interleukin 5 genetic background in atopic dermatitis patients:
      significant difference between those with blood eosinophilia and normal
      eosinophil levels.
AB  - BACKGROUND: Blood eosinophil levels in patients with atopic dermatitis vary
      widely during exacerbation of the disease. We considered that in addition to
      environmental factors, the genetic background involved with elevating blood
      eosinophil levels might be heterogeneous among atopic dermatitis patients.
      OBJECTIVE: We attempted to determine whether a polymorphism of the interleukin
      (IL)5 gene plays a role in atopic dermatitis, particularly in those patients with
      blood eosinophilia. Due to the close relation of blood eosinophilia to high IgE
      productivity, we also assessed these polymorphisms in patients with high IgE
      concentrations. METHODS: We determined the genotype of the IL5 polymorphism 
      703C/T in 451 atopic dermatitis patients and 116 normal subjects. The patients
      were classified into three groups by blood eosinophil levels; less than 7%, from
      7 to 15%, and more than 15%, as well as by serum IgE concentrations; less than
      500 IU/ml, from 500 to 2000 IU/ml, and more than 2000 IU/ml. RESULTS: IL5 -703C/T
      was not significantly associated with either total atopic dermatitis patients or
      individual patients who had both blood eosinophilia and high IgE productivity.
      However, the distribution of the IL5 -703C/T genotype was significantly different
      between patients with either blood eosinophilia or high IgE productivity and
      those without either condition (P=0.0476, P=0.0088, respectively). CONCLUSION:
      These results suggest that the IL5 gene may play a role in blood eosinophilia
      associated with atopic dermatitis. We also considered that the IL5 -703C/T gene
      polymorphism does not have a direct relationship to disease specificity.

PMID- 14581139
TI  - Emollient cream and topical glucocorticoid treatment of chronic hand dermatitis:
      influence on oxidative stress status of the skin.

PMID- 14581140
TI  - Lack of association of CCR3 single nucleotide polymorphism with atopic dermatitis
      in Japanese population.

PMID- 14581141
TI  - Developmental expression of mafB messenger ribonucleic acids in rat skin by in
      situ hybridization histochemistry.

PMID- 14581142
TI  - Substance P prolongs human hair growth in vitro.

PMID- 14581143
TI  - Effects of an aldose reductase inhibitor on gastroenteropathy in streptozotocin
      diabetic rats.
AB  - We investigated the effects of epalrestat, an aldose reductase inhibitor (ARI),
      on gastric emptying, fecal water content, and electrolyte transport in distal
      colon in streptozotocin (STZ)-induced diabetic rats. We measured gastric emptying
      time by acetaminophen method and short-circuit-current (Isc) in colonic mucosa
      using an Ussing chamber. The Isc in response to electric-field-stimulation (EFS)
      was decreased in untreated rats due to suppression by Cl- secretion. ARI
      treatment alleviated this suppression (2.7 +/- 0.6 vs. 7.4 +/- 1.1 microA/0.38
      cm2 at 8 weeks after treatment, 1.1 +/- 0.2 vs. 7.0 +/- 1.0 at 12 weeks after
      treatment, P<0.05). In addition, the percentage of fecal water content in
      untreated rats was significantly lower than in ARI-treated rats (58.0 +/- 2.0 vs.
      67.6 +/- 0.8% at 8 weeks, 56.9 +/- 2.1 vs. 63.4 +/- 1.4 at 12 weeks, P<0.05).
      From STZ injection to 8 weeks, the serum levels of acetaminophen in the diabetic
      rats were significantly lower than in controls, indicating delayed gastric
      emptying. At 12 weeks in the diabetic rats treated with ARI, the serum levels of
      acetaminophen were significantly higher than in the untreated diabetic rats (6.6
      +/- 0.4 vs. 3.5 +/- 0.5 microg/ml, P<0.05). ARI-treatment ameliorated delayed
      gastric emptying without improving glycemic control. These findings show that ARI
      partially prevented progression of impaired gastric emptying, ion transport, and
      water transport, and suggest that epalrestat might be useful in the treatment of
      diabetic gastroenteropathy.

PMID- 14581144
TI  - Comparison of lunch and bedtime NPH insulin plus mealtime insulin Lispro therapy
      with premeal regular insulin plus bedtime NPH insulin therapy in type 2 diabetes.
AB  - AIM: Nonfasting plasma glucose is claimed to be a better marker of diabetic
      control than fasting plasma glucose in type 2 diabetes. In this study we compared
      the efficacy and safety profile of two different intensive insulin treatment
      strategies in patients with uncontrolled type 2 diabetes despite using a twice
      daily insulin regimen. METHODS: We studied 60 insulin-treated patients who had
      uncontrolled type 2 diabetes. The study was a 6-month, open-label, randomised,
      parallel clinical trial conducted in two diabetes centres. The main end-points
      for analysis were weekly self-monitored blood glucose readings, HbA1c levels,
      total daily insulin dose, weight gain and the number of hypoglycaemic episodes.
      RESULTS: The breakfast 2-h, lunch 2-h and dinner 2-h postprandial glucose values
      and pre-dinner glucose values were significantly lower in the Lispro group than
      the regular insulin group. The HbA1c value at the end of the study was
      significantly lower in the Lispro group (7.3 +/- 0.7%) compared with the regular
      insulin group (7.7 +/- 0.7%; P<0.05). Mean insulin doses were similar in the
      treatment groups initially and at the end. There was a statistically significant
      increase in insulin dose in both groups from baseline to the end of the study
      (P<0.05). Overall hypoglycaemia rates were comparably low and similar in both
      groups during the study. CONCLUSIONS: We have shown that mealtime insulin Lispro
      plus additional lunch and bedtime NPH insulin is superior to premeal regular
      insulin plus bedtime NPH insulin for overall glycaemic regulation with similar
      weight gain and comparable rates of hypoglycaemia.

PMID- 14581145
TI  - Improvement of insulin resistance by a new insulin secretagogue, nateglinide-
      analysis based on the homeostasis model.
AB  - Type 2 diabetes is a heterogeneous disorder characterized by defects in the early
      phase of insulin secretion after meals and in insulin resistance at its early
      stage. A new insulin secretagogue, nateglinide, has been shown to elicit an acute
      insulin release and to reduce postprandial hyperglycemia. We have treated 30
      patients with type 2 diabetes using nateglinide and performed a standard meal
      test at breakfast, both before and after the treatment. Insulin resistance and
      beta-cell function was assessed by the HOMA model. Nateglinide, at 1 and 2 h
      after the test meal, significantly stimulated postprandial insulin secretion by
      62.0 and 41.0% and improved blood glucose values by 17.3 and 21.9%, respectively,
      after the treatment. Fasting blood glucose (FBG) and glycohemoglobin was
      significantly reduced by 9.8 and 10.3%, respectively. The reduction was
      significantly larger in postprandial glucose than in FBG (P<0.0005). A
      significant correlation was found in the HOMA-insulin resistant (IR) index and in
      the changes of fasting IRI. When the patients were divided into three groups,
      forming a markedly insulin resistant (MIR) group, an IR group and a non-insulin
      resistant (NIR) group, HOMA-IR levels improved significantly, from 7.0 +/- 4.3 to
      4.5 +/- 2.8 (P=0.026) in the MIR group and showed a tendency toward improvement
      in the IR group, from 2.9 +/- 0.7 to 2.3 +/- 1.1 (P=0.062), but failed to exhibit
      such a positive response in the NIR group, changing from 1.2 +/- 0.2 to 1.9 +/-
      0.9 (P=0.21). HOMA-beta, on the other hand, improved significantly in the NIR
      group only, from 16.4 +/- 7.8 to 26.9 +/- 9.9 (P=0.017), but not in the IR nor
      MIR groups (M +/- S.D.). In conclusion, nateglinide improved the excessive
      excursion of postprandial glucose by the augmentation of early insulin secretion
      after a meal and differentially affected fasting insulin levels and HOMA-IR
      indexes, depending on the degree of insulin resistance.

PMID- 14581146
TI  - Higher prevalence of type 2 diabetes, metabolic syndrome and cardiovascular
      diseases in gypsies than in non-gypsies in Slovakia.
AB  - OBJECTIVE: Gypsies (or Roma) recently experienced a transition from a traditional
      to a Westernized lifestyle. Although mortality in this population is 4-fold
      higher compared with non-Gypsies, very limited information is available on their
      morbidity especially with regard to non-communicable diseases. Our aim was to
      determine the prevalence of type 2 diabetes mellitus (T2DM), metabolic syndrome
      and cardiovascular diseases in Gypsies and non-Gypsies living in the same region
      of southern Slovakia. MATERIALS AND METHODS: We examined 156 Gypsies and 501 non
      Gypsies who participated in a population survey. Age- and sex-standardized
      prevalence rates were computed for each of the following: T2DM, obesity,
      hyperlipidemia, hypertension, hyperinsulinemia, elevated albumin/creatinine ratio
      (ACR), metabolic syndrome and cardiovascular disease. RESULTS: Age-sex
      standardized prevalence of T2DM was 30% (95% CI=22-39) in Gypsies and 10% (8-13,
      P=0.0001 for comparison of ethnic groups) in non-Gypsies. Corresponding
      prevalence of the other variables are: 65% (56-74) and 30% (26-34, P=0.0001) for
      obesity, 69% (61-76) and 59% (54-63, P=0.04) for hypercholesterolemia, 66% (59
      74) and 39% (35-43, P=0.009) for hypertriglyceridemia, 49% (42-56) and 43% (39
      47, P=0.1) for hypertension, 33% (26-50) and 8% (2-14, P=0.002) for
      hyperinsulinemia, 16% (9-22) and 5% (3-7, P=0.0001) for elevated ACR, 20% (12-27)
      and 4% (3-6, P=0.0001) for metabolic syndrome and 35% (28-43) and 26% (22-29,
      P=0.004) for cardiovascular disease. CONCLUSIONS: Compared with non-Gypsies,
      Gypsies had a much higher prevalence of T2DM, metabolic syndrome and
      cardiovascular disease, which may contribute to their higher mortality.

PMID- 14581147
TI  - The Pro12Ala polymorphism of PPARgamma2 gene and susceptibility to type 2
      diabetes mellitus in a Polish population.
AB  - INTRODUCTION: It has recently been shown that polymorphisms of some genes might
      influence the genetic susceptibility to complex, multifactorial forms of type 2
      diabetes mellitus (T2DM). One of those genes is peroxisome proliferator activated
      receptor gamma (PPARgamma). The PPARgamma gene product is a nuclear hormone
      receptor that regulates adipogenesis and is a target for thiazolidinediones,
      medications enhancing sensitivity to insulin. The Pro12Ala amino acid variant of
      the PPARgamma2 isoform is associated with T2DM in several populations. AIMS: (1)
      To determine the allele and genotype frequency of the Pro12Ala PPARgamma2 amino
      acid variant in a Polish population; (2) To search for the association of the
      Pro12Ala polymorphism with T2DM in the examined population. METHODS: We included
      644 individuals in this study: 366 T2DM patients with age of diagnosis greater
      than 35 years and 278 non-diabetic control subjects. The fragment of the
      PPARgamma2 gene which contains the examined amino acid variant was amplified by
      polymerase chain reaction (PCR). Alleles and genotypes were determined based on
      electrophoresis of the DNA digestion products by the specific restriction enzyme
      BshI. Differences in distribution between the groups were examined by chi2 test.
      RESULTS: The frequency of Pro/Ala alleles was similar in T2DM patients and in the
      control subjects (83.5%/16.5% vs. 84.5%/15.5%, respectively, P=0.607). Similarly,
      there was no difference between the groups when we analysed the genotype
      distribution. Stratification analyses based on age of diagnosis, body mass index
      (BMI), and family history of T2DM were performed. The Pro/Ala and Ala/Ala
      genotypes tended to be more frequent in T2DM cases with age of diagnosis >50
      years than in controls (36.2% vs. 27.3%, P=0.046). This difference was not
      significant after Sheffe correction for multiple comparisons. The other
      stratification analyses did not show any difference between the groups.
      CONCLUSION: The frequency of the Pro12Ala PPARgamma2 polymorphism in the Polish
      population studied is similar to that in other Caucasian populations. In the case
      control study, we were not able to confirm earlier reports that the Pro allele
      conferred an increased risk for development of T2DM. Moreover, the results of the
      stratified analysis suggest an opposite trend in late onset T2DM.

PMID- 14581148
TI  - No increased risk of developing depression in diabetes compared to other chronic
      illness.
AB  - Several studies have found that the prevalence of depression in patients with
      diabetes is higher than in the general population but it is unclear whether
      patients with diabetes have an increased risk of developing depression compared
      with patients with other chronic illnesses. In a nationwide case register study,
      all patients who had a discharge diagnosis of diabetes or of osteoarthritis at
      first admission in a period from 1977 to 1997 were identified. The probability of
      being readmitted and discharged with a diagnosis of depression was estimated with
      competing risks models in survival analysis. In total, 91,507 patients with a
      diagnosis of diabetes at first discharge and 108,487 patients with a diagnosis of
      osteoarthritis were identified. The median age of the populations was high. No
      difference in the risk of being readmitted with a diagnosis of depression was
      found between the two groups of patients. There was no difference in the risk for
      Type 1 and Type 2 diabetes. It is concluded that older patients with diabetes do
      not seem to have an increased risk of developing severe depression compared with
      patients with other chronic illness.

PMID- 14581149
TI  - Translation of the recommendations for the diagnosis of diabetes mellitus into
      daily clinical practice in a primary health care setting.
AB  - AIMS: to assess the implementation of 1985 recommendations for the diagnosis of
      diabetes (World Health Organization [WHO]) in a primary care setting, and the
      physician's attitude toward the diagnosis of diabetes mellitus (DM). MATERIAL AND
      METHODS: Subjects with a fasting plasma glucose (FPG)>6.1 mmol/l (> or =110
      mg/dl) and with previously unknown glucose tolerance status were identified
      retrospectively in a primary health care center during a 45-month period. The
      following variables were evaluated: anthropometric parameters, fasting plasma
      glucose and oral glucose tolerance test (OGTT) values, registration of a
      diagnosis of diabetes in clinical records, smoking status, lipid profile and
      blood pressure. RESULTS: 1181 subjects with a FPG>6.1 mmol/l were identified
      (target population): 171 with a FPG>7.8 mmol/l and 1010 with a FPG between 6.1
      and 7.7 mmol/l. In the latter group, an OGTT was performed in 553 subjects
      (54.8%) (173 yielded a diagnosis of diabetes). During the study period, diabetes
      was diagnosed in 29.1% (n=344) of the target population. Following the 1985 WHO
      recommendations, a confirmatory diagnostic test was repeated in 92 (69.7%)
      subjects with a FPG between 7.8 and 11.0 mmol/l, and in 132 subjects (23.87%) who
      had already received an initial OGTT. The analysis of the diagnostic process
      followed by the different physicians revealed a high interindividual variability
      in terms of: proportion of cases diagnosed as diabetes by an OGTT (from 35.7 to
      65.2), percentage of subjects with a FPG 6.1-7.7 mmol/l without an OGTT (7.33
      70.27%), proportion of confirmatory OGTTs (0-57.89%), and percentage of
      misdiagnosed cases (1.16-6.34%). The percentage of subjects misdiagnosed was
      negatively correlated with the proportion of OGTT repetitions. CONCLUSIONS: 1985
      WHO recommendations for the diagnosis of diabetes are only partially followed at
      a primary health care level. There is a high interindividual variability among
      physicians in the implementation of these recommendations that is associated with
      the misdiagnosis of diabetes.

PMID- 14581150
TI  - Prevalence and risk factors for gestational diabetes assessed by universal
      screening.
AB  - In order to evaluate the prevalence of gestational diabetes mellitus (GDM) and
      the presence of risk factors for GDM, we conducted a retrospective study of a
      cohort of Italian women. In addition, we compared universal versus selective
      screening to validate the ADA's recommendations in our population. From June 1st,
      1995 to December 31st, 2001, universal screening for GDM was performed in 3950
      women. The glucose challenge test (GCT) was positive (GCT+) in 1389 cases
      (35.2%). The 1-h glucose level after GCT enabled us to diagnose GDM directly in
      24 pregnant women. Oral glucose tolerance test (OGTT) was performed in 1221 GCT+
      women (144 cases with GCT+ dropped out) and GDM was diagnosed in 284 (23.2%) of
      them. OGTT was also performed in 391 randomly chosen, women from the GCT negative
      (GCT-) group. In this last group 25 (6.3%) women had GDM. Thus, the total number
      of subjects with GDM was 333 out of 3806 with a prevalence of 8.74% in the entire
      cohort. Assuming that the rate of GDM observed in the random sample of GCT- women
      is applicable to the whole group of 2561 GCT- women, then 161 GCT- patients could
      also have GDM. This will further increase the estimated prevalence for the whole
      cohort up to 12.3% (i.e. 469 out of 3806 pregnant women). There were 236 (5.6%)
      women with a low risk for GDM (normal weight, age less than 25 years and without
      a family history of diabetes). In this group we found 34 cases and five cases
      with positive screening test and GDM, respectively. Thus, if we excluded low risk
      women from the screening test, as suggested by ADA recommendations, only five
      women with GDM would have been missed. However, about 95% of our population were
      at medium or high risk for GDM and, therefore, would have been screened. The rate
      of GDM was significantly higher in women with a positive history of diabetes,
      increasing age, previous pregnancies, pre-pregnancy overweight and short stature.
      After logistic regression analysis, GDM diagnosis was significantly correlated
      with age (P<0.0001), pre-pregnancy BMI (P<0.0001), weight gain (P<0.0001) and
      family history of diabetes (P<0.01).

PMID- 14581152
TI  - Subjective health values of individuals with diabetes in Japan: comparison of
      utility values with the SF-36 scores.
AB  - To investigate the characteristics of utility values for current health states
      and the Medical Outcome Study Short Form 36 (SF-36) scores in terms of patients'
      preferences, we performed the utility assessment using the visual analog scale
      (VAS) and the standard gamble (SG) techniques, and the SF-36 questionnaires on 68
      hospitalized individuals with diabetes. Sixty patients responded appropriately.
      The SG value, 0.93 +/- 0.12 (mean +/- S.D.), was significantly higher than the
      VAS value, 0.65 +/- 0.21 (P<0.001). A tendency for the SF-36 subscale scores to
      decrease compared to national normative data for Japan was observed. Diabetic
      conditions such as glycated hemoglobin level and daily insulin injection were not
      significant predictors of either utility or SF-36 scores, while diabetic
      complications affected two subscales of the SF-36. The VAS values were somewhat
      related to the SF-36 subscale scores but the SG values had no relation to any SF
      36 scores. These results suggest the difficulty of estimating the subjective
      health values of the patients only through the traditional clinical indicators
      and the SF-36 scores.

PMID- 14581151
TI  - Peroxisome proliferator-activated receptor gamma mediated inhibition of
      plasminogen activator inhibitor type 1 production and proliferation of human
      umbilical vein endothelial cells.
AB  - Insulin resistance and diabetes mellitus promote the atherosclerotic process,
      where an endothelial dysfunction plays a key role. The diabetic milieu elevates
      the production of the plasminogen activator inhibitor type 1 (PAI-1) and also
      increases the proliferation of vascular endothelial cells. Recently the role of
      peroxisome proliferator-activated receptor gamma (PPARgamma) in atherosclerosis
      has been extensively studied. However, the direct effect of PPARgamma in vascular
      endothelial cells is still unclear. Therefore, the effect of PPARgamma was
      investigated to determine if it plays an important role in PAI-1 production and
      cellular proliferation in human umbilical vein endothelial cells (HUVEC). A
      combination of PPARgamma-overexpression and troglitazone treatment (5 ug/ml)
      significantly decreased both the PAI-1 mRNA and protein expression, while
      PPARgamma-overexpression or troglitazone alone tended to decrease both the PAI-1
      protein and mRNA expression. PPARgamma-overexpression or troglitazone treatment
      alone reduced the thymidine uptake by the HUVEC with or without TNFalpha
      treatment. There was a further decrease in the thymidine uptake with troglitazone
      treatment in the PPARgamma-overexpressed HUVEC. In conclusion, PPARgamma can
      reduce PAI-1 production in HUVEC directly by transcriptional repression, and may
      play a beneficial role in preventing cardiovascular events. PPARgamma can also
      inhibit vascular endothelial cell proliferation, and its clinical relevance in
      diabetic vascular complications should be elucidated.

PMID- 14581153
TI  - Relationship between hyperinsulinemia and pulse wave velocity in moderately
      hyperglycemic patients.
AB  - AIM: Arterial stiffness assessed by pulse wave velocity (PWV) reflects early
      stage arteriosclerosis. The influence of hyperinsulinemia on peripheral vascular
      disease (PVD) is still unknown. We determined the influences of hyperinsulinemia
      on PVD assessed by PWV in moderately hyperglycemic patients. METHODS: Thirty-six
      moderately hyperglycemic, outcoming patients were recruited in this study. All
      subjects were divided into two groups by fasting immunoreactive insulin (F-IRI)
      concentrations; group A; F-IRI> or =5 microU/ml, group B; F-IRI<5 microU/ml. Both
      hbPWV (from heart to brachial artery) and baPWV (brachial to artery to ankle)
      were evaluated by using Form PWV/ABI, in addition to ankle-brachial pressure
      index (ABPI). RESULTS: In group A, both hbPWV and baPWV showed significantly
      higher values than in group B. ABPIs were not different between two groups.
      Although age, FPG, plasma HbA1c, serum total-cholesterol, HDL-cholesterol
      concentrations, and systolic and diastolic blood pressure were at same levels in
      group A as group B, body mass index, HOMA-R, serum triglyceride concentrations
      were significantly higher in group A, indicating the existence of insulin
      resistance in group A. CONCLUSION: Hyperinsulinemia may be involved in the
      development of PVD in moderately hyperglycemic patients.

PMID- 14581154
TI  - Impact of a critical pathway on inpatient management of diabetic ketoacidosis.
AB  - To assess the management of diabetic ketoacidosis (DKA) and evaluate if
      introduction of a critical pathway improves management, we studied adults
      admitted with DKA to the Medicine and Critical Care Services in a US teaching
      hospital. Patients admitted with DKA in 1997 before implementation of the
      critical pathway were the control group (n=72). In 1998, housestaff and nurses in
      the emergency department (ED) and on the General Medicine and Critical Care
      Services were instructed in the use of the critical pathway. Patients admitted
      with DKA during 1998 (n=77) were the intervention group. Length of stay (LOS),
      hospital cost, adherence to guidelines, and medical outcomes to be avoided were
      compared, and regression analyses were performed to correlate processes and
      outcomes of care. Mean LOS and variability in LOS decreased during the
      intervention period, especially in patients treated without endocrinology
      consultation (EC) (5.2 +/- 10.6 vs. 2.4 +/- 2.1 days, P=0.01), and hospital cost
      and variability in cost tended to decrease ($6441 +/- 15,204 vs. $3625 +/- 3478,
      P=0.24). More intervention subjects received the recommended intravenous fluid
      volume (88 vs. 71%, P=0.013), education in sick-day management (77 vs. 54%,
      P=0.006), and EC (38 vs. 21%, P=0.03). Insulin management was not changed. We
      conclude that implementation of a DKA critical pathway reduced practice variation
      and was associated with shorter LOS and a trend toward decreased cost. Some
      processes of care were improved but many require additional interventions.

PMID- 14581155
TI  - Association of fulminant type 1 diabetes with pregnancy.
AB  - It has been reported that fulminant type 1 diabetes is a novel subtype of type 1B
      diabetes. However, whether the etiology of fulminant type 1 diabetes is
      associated with an autoimmune or nonautoimmune process remains to be solved. In
      order to further characterize fulminant type 1 diabetes, we compared the
      clinical, immunological and genetic characteristics with those of acute-onset
      type 1A diabetes. Nine patients with fulminant diabetes and nine patients with
      acute-onset type 1A diabetes, who had been newly diagnosed during 1998-2001, were
      analyzed. In female patients of child-bearing age, the onset of diabetes occurred
      during pregnancy or after delivery in three cases of six fulminant cases, but not
      in any of seven type 1A diabetes. Eight of nine fulminant patients had fever
      immediately prior to the onset of hyperglycemic symptoms, whereas only one of
      nine type 1A patients had this (P=0.002). In Japanese type 1 susceptible HLA
      haplotypes, DRB1*0901-DQB1*0303 was more frequent in type 1A diabetes than
      fulminant diabetes (7/18 vs. 0/18, P=0.004), whereas the frequency of DRB1*0405
      DQB1*0401 was similar (type 1A 4/18 vs. fulminant 6/18). Therefore, pregnancy,
      possible viral infection, or HLADRB1*0405-DQB1*0401 may contribute to the onset
      of fulminant type 1 diabetes.

PMID- 14581156
TI  - Gender differences in the effect of type 2 diabetes on serum lipids, pre-heparin
      plasma lipoprotein lipase mass and other metabolic parameters in Japanese
      population.
AB  - DESIGN: Cross-sectional study of fasting serum lipid and lipoprotein levels, pre
      heparin lipoprotein lipase (LPL) mass, several other metabolic parameters, and
      intra-abdominal fat areas in 26 Japanese poorly controlled type 2 diabetic men
      and 23 women when matched for age, body mass index (BMI), and HbA1c between
      genders. SUBJECTS: Study subjects were Japanese type 2 diabetic patients who were
      admitted to our hospital between Jun 2001 and Aug 2002 because of their poorly
      controlled diabetes. A total of 49 subjects [40-79 years of age, average age 61.5
      +/- 8.7; mean BMI 23.2 +/- 3.7 kg/m2] with fasting plasma glucose (PG) and HbA1c
      levels being 251 +/- 76.5 mg/dl and 10.8 +/- 2.2%, respectively, were involved in
      this study. METHODS: Pre-heparin LPL mass was determined by enzyme linked
      immunosorbent assay. Remnant like particle cholesterol (RLP-C) level was measured
      using an immunoaffinity mixed gel containing anti-apolipoprotein (apo) A-I and
      anti-apo B monoclonal antibodies. Serum leptin level was determined by
      radioimmunoassay. Intra-abdominal fat area was determined by computerized
      tomography analysis at the umbilical level. RESULTS: The men group showed a
      higher serum triglycerides (TG) and RLP-C levels, and lower high density
      lipoprotein-cholesterol levels and pre-heparin plasma LPL mass than did women.
      Serum leptin level was higher in women than in men counterparts. The intra
      abdominal subcutaneous fat areas were significantly larger in women than in men
      counterparts, whereas the visceral fat areas did not differ. CONCLUSION: In
      Japanese population, poorly controlled type 2 diabetic men had more unfavorable
      lipid profile than did women counterparts, which may be associated with decreased
      lipolysis of plasma TG-rich lipoproteins by LPL.

PMID- 14581157
TI  - Screening tests for gestational diabetes in Japan in the 1st and 2nd trimester of
      pregnancy.
AB  - The objective of this study was to investigate the utility and characteristics of
      various screening procedures for gestational diabetes mellitus (GDM) in Japan
      during the first trimester and between 24 and 28 weeks of pregnancy. The subjects
      were 749 pregnant women who came to our hospitals. A 50-g oral glucose challenge
      test (GCT), casual plasma glucose measurements, fasting blood glucose
      measurements, and glycosylated hemoglobin measurements were performed in the
      first trimester. Subjects with no abnormalities were tested again at 24-28 weeks
      of gestation. Of the 749 subjects, 22 (2.9%) tested positive for GDM. Of those 22
      patients, 14 were diagnosed with GDM in the first trimester (63.6%) and eight in
      the second trimester (36.4%). This finding suggests the importance of screening
      for glucose intolerance in the first trimester. Furthermore, it appears that the
      GCT has the most utility for GDM screening; the other screening methods tested
      were not as useful because of their low sensitivity, particularly in the second
      trimester.

PMID- 14581158
TI  - The association of Pro12Ala polymorphism in PPARgamma2 with lower carotid artery
      IMT in Japanese.
AB  - In this study, the association of the Pro12Ala peroxisome proliferator-activated
      receptor gamma2 (PPARgamma2) polymorphism with atherosclerosis was examined in a
      Japanese Type 2 diabetic population. PPARgamma has been identified as a key
      regulator of adipogenesis. Recently, some studies reported that the Pro12Ala
      polymorphism was associated with resistance to Type 2 diabetes. It is well-known
      that Type 2 diabetes is closely related with disorder of lipid metabolism as well
      as impaired glucose homeostasis, resulting in atherosclerosis. We aimed to
      evaluate the association between carriers of the Pro12Ala PPARgamma2 mutation and
      clinical profiles concerning atherosclerosis besides plasma glucose and lipid
      concentrations. Screening for the mutation was performed using the polymerase
      chain reaction-restriction fragment length polymorphism (PCR-RFLP) method among
      154 Type 2 diabetic patients. The homozygotes of the Pro12 allele were 143 (93%),
      the heterozygotes of the Pro12 and Ala12 allele were 11 (7%) and the homozygote
      of the Ala12 allele was not detected. The group with the Ala12 allele had a
      significantly lower value of carotid artery intima-media thickness (IMT) than
      that without it, although there was no difference between two groups in sex, age
      or other clinical variables we examined. The Pro12Ala PPARgamma2 polymorphism may
      be associated with carotid artery IMT values in Type 2 diabetes mellitus.

PMID- 14581159
TI  - Inadequacy of therapeutic education: a risk factor of hypoglycaemia.

PMID- 14581160
TI  - Monotherapy of type 2 diabetes with once-daily gliclazide modified release in
      primary care.

PMID- 14581161
TI  - Topical phytochemicals used to salvage the gangrenous lower limbs of type 1
      diabetic patients.

PMID- 14581162
TI  - Hypothermia attenuates delayed cortical cell death and ROS generation following
      CO inhalation.
AB  - Carbon monoxide (CO) is the most popular cause of poisoning. The bilateral basal
      ganglia lesion characterizes the delayed neuronal cell death (DCD). We
      demonstrated there were both apoptosis and necrosis in the cortex, basal ganglia
      and hippocampus in a case of human CO accident. To elucidate the mechanism of DCD
      after CO inhalation, histological studies on the rat brain were conducted. Rats
      were ventilated with nitrous oxide (sham group), 10% O(2) (hypoxia group) or 1005
      ppm CO (CO group) for 90 min, while the pericranial temperature was controlled at
      either 32, 37, or 39 degrees C during CO inhalation. After reoxygenation for 30
      min, the rats were allowed to recover for 48 h. The ratio of eosinophilic and HNE
      positive neurons in the cortex were higher in the CO group than in the hypoxia
      group at 37 degrees C, while the PaO(2) was much lower in the hypoxia than in the
      CO group. The damage was alleviated in the hypothermia (32 degrees C) as compared
      with normothermia, while the hyperthermia (39 degrees C) did not significantly
      increased it. CO inhalation injures neuron by reactive oxygen species (ROS),
      independent of hypoxia, as can be concluded from the histological comparison of
      DCD with HNE immunoreactivity.

PMID- 14581163
TI  - Toxicological evaluation of dry ice expanded tobacco.
AB  - A tiered testing strategy has been developed to evaluate the potential of tobacco
      processes, ingredients, or technological developments to change the biological
      activity resulting from burning tobacco. The strategy is based on comparative
      chemical and biological testing. Dry ice expanded tobacco (DIET) is an example of
      a common tobacco expansion process currently used in the manufacture of
      cigarettes to increase tobacco filling capacity. As part of the toxicological
      evaluation of DIET, test cigarettes containing DIET were compared with control
      cigarettes containing tobacco expanded with a traditional expansion agent (Freon
      11, also known as trichlorofluoromethane). Testing included mainstream cigarette
      smoke chemistry studies, genotoxicity studies (Ames and sister chromatid
      exchange, SCE), a 13-week inhalation study in Sprague-Dawley rats, and a 30-week
      dermal tumor promotion study in SENCAR mice. Cigarettes containing DIET or Freon
      11 expanded tobacco were similar in biological activity.

PMID- 14581164
TI  - Induction of redox changes, inducible nitric oxide synthase and cyclooxygenase-2
      by chronic cadmium exposure in mouse peritoneal macrophages.
AB  - Redox changes and the secretion of inflammatory mediators were investigated in
      resident peritoneal macrophages of mice chronically exposed to cadmium (Cd, 15
      ppm for 2 months) through drinking water. Our results showed that in vivo Cd
      exposure altered the redox balance in mouse peritoneal macrophages, leading to
      excessive production of reactive oxygen species (ROS) that overwhelmed the
      antioxidant defenses. It also led to increased lipid peroxidation and arachidonic
      acid (AA) release, higher nitric oxide and prostaglandin E(2) (PGE(2))
      production, and induction of inducible nitric oxide synthase and cyclooxygenase-2
      compared with control macrophages. Oxidative stress and inflammation could be
      important processes operating in the modulation of mouse macrophage physiology
      induced by chronic Cd exposure.

PMID- 14581166
TI  - Increase of rat medial habenular mast cell numbers by systemic administration of
      cyclophosphamide.
AB  - Cyclophosphamide administration generates systemic toxicity having immune and
      nervous consequences. After focusing on nervous consequences by studying neuronal
      activity, we now consider cyclophosphamide impact on diencephalic mast cells as
      part of the brain immune system. Diencephalon, the ultimate sensory relay before
      neocortical processing, is the only brain structure containing mast cells. Single
      cyclophosphamide administration (100 mg/(kg 1 ml ip)) was performed in naturally
      behaving rats and diencephalic mast cell numbers were analyzed once all drug
      effects had developed (4 h postinjection). Significant increases were observed
      only in the medial habenular nucleus--bilaterally and especially in its caudal
      portion. Mast cell increase is temporally related to behavioral impairment and
      evoked neuronal activity in a restricted number of visceral/limbic extrathalamic
      structures. The medial habenular nucleus belongs to the limbic system involved in
      processing emotional reactions and regulation of the autonomic nervous system.
      Its involvement during toxic challenge is highly compatible with its presumed
      function in the maintenance of vital functions.

PMID- 14581165
TI  - Liposomal photofrin enhances therapeutic efficacy of photodynamic therapy against
      the human gastric cancer.
AB  - Photodynamic therapy (PDT) has been established as a potent and less invasive
      treatment for gastrointestinal tumors. The aim of the present study was to
      investigate whether or not liposomalization of the photosensitizer enhanced the
      therapeutic efficacy of PDT. Photofrin (PF) was entrapped in multilammelar
      liposomes. Mice implanted with a human gastric cancer xenograft, were divided
      into a PF group and a liposomal photofrin (LPF) group and intravenously
      administered 10 mg/kg of PF or LPF (as a dose of PF), respectively. At 8 h after
      injection PF level in tumor tissue in the LPF group was significantly higher
      level by 2.4-fold of that in the PF group, whereas the PF levels in the skin were
      almost equal. Irradiation was performed with the excimer dye laser at 150
      mW/cm(2), total dose 40 J, at 8 h after PF or LPF administration. The results
      revealed that the volume of necrotic tumor tissue was significantly higher in the
      LPF group than in the PF group. The apoptotic index of the tumor was also
      significantly higher in the LPF group. In conclusion, the liposomalization of the
      photosensitizer increased its tumor accumulation, with a resulting enhancement of
      the therapeutic effect of PDT.

PMID- 14581167
TI  - Rubratoxin B induced the secretion of hepatic injury-related colony stimulating
      factors in human hepatoma cells.
AB  - The induction of cytokine secretion by rubratoxin B was investigated using human
      hepatoma cell lines HepG2 and HuH-7. Interleukin (IL)-8, macrophage colony
      stimulating factor (M-CSF) and granulocyte-macrophage (GM)-CSF were detected in
      the media of rubratoxin B-treated both cell lines, and their levels peaked at
      about 40 microg/ml. Rubratoxin B-induced cytokine secretion was enhanced by tumor
      necrosis factor (TNF)-alpha in HepG2 cells. While emodin increased GM-CSF
      secretion, the secretion of the others was decreased, indicating that they are
      regulated differently in rubratoxin B-treated HepG2 cells. To our knowledge, this
      is the first report that an exogenous stimulus induced the secretion of M-CSF and
      GM-CSF in hepatocyte-derived hepatoma cells, suggesting that rubratoxin B is an
      excellent model compound to study the mechanisms of M-CSF and GM-CSF secretion.
      Our results showed that hepatotoxin rubratoxin B has a potential to induce the
      secretion of these two CSFs, implying that these factors play roles in rubratoxin
      B-caused hepatic injury.

PMID- 14581168
TI  - Zinc benzoate, a contaminating environmental compound derived from polystyrene
      resin inhibits A-type monoamine oxidase.
AB  - The contaminants in deionized and distilled water (DDI water) boiled with
      polystyrene resin inhibited A-type monoamine oxidase (MAO, MAO-A preferentially
      deaminates serotonin and norepinephrine and regulates these amines concentration)
      activity in monkey brain mitochondria. To identify these contaminants, we
      attempted measurements by HPLC, FT-IR and NMR. The compound inhibiting MAO-A
      activity was zinc benzoate. Although it potently inhibited MAO-A activity, zinc
      benzoate did not effect MAO-B in monkey brain mitochondria. It also reversibly
      and competitively inhibited MAO-A activity in a dose-dependent manner. Zinc
      benzoate, however, did not inhibit either MAO-A or -B activities in rat brain
      mitochondria. These results indicate that zinc benzoate, which inhibits MAO-A
      activity, is easily incorporated in DDI water by boiling polystyrene and also may
      be a contaminating environmental chemical compound that alters the levels of
      serotonin and norepinephrine in the central nervous system.

PMID- 14581169
TI  - Effects of dietary folate intake and folate binding protein-1 (Folbp1) on urinary
      speciation of sodium arsenate in mice.
AB  - In most mammalian species, arsenic biotransformation occurs primarily by
      biomethylation with dimethylarsinic acid being the predominant metabolite
      excreted in the urine. Folbp1 (folate binding protein-1) mediated intracellular
      folate uptake is one route by which cells harvest folate cofactors. In light of
      the likely relationship between folate biochemistry and arsenic
      biotransformation, our experiments were designed to test: (1) whether Folbp1 is
      an important determinant in arsenic biotransformation, by performing urinary
      arsenic speciation in Folbp1 nullizygous (Folbp1(-/-)) and wildtype control mice,
      and (2) whether dietary folate deficiency alters arsenic biotransformation in
      these mice. Compared to normal folate intake, folate deficiency caused lower
      amounts of arsenic to be excreted in the urine of both the wildtype controls and
      Folbp1(-/-) mice. Folbp1(-/-) mice excreted more dimethylarsinic acid than
      wildtype control mice during folate deficiency, but not during normal folate
      intake. The present data suggest that inadequate folate intake may result in
      decreased biotransformation and excretion of arsenic, which is likely to increase
      arsenic exposure and related toxicities.

PMID- 14581171
TI  - Oxidative damage of DNA induced by methylglyoxal in vitro.
AB  - Methylglyoxal is an endogenous metabolic by-product of glycolysis and has
      genotoxic effects. Previous studies suggested that the reaction of methylglyoxal
      with amino acid leads to the production of free radicals. In this study,
      oxidative damage of DNA by the reaction of methylglyoxal with amino acid was
      investigated. When plasmid DNA was incubated with methylglyoxal and lysine, DNA
      strand was cleaved. Cu(2+) enhanced DNA strand breakage induced by the reaction
      of methylglyoxal with lysine. The formation of superoxide anion was detected
      during the glycation reaction of methylglyoxal with lysine. Radical scavengers,
      catalase, and copper chelators inhibited the DNA breakage. The deoxyribose assay
      showed that hydroxyl radicals were generated during the reaction of methylglyoxal
      with lysine in the presence of Cu(2+). The generation of hydroxyl radicals was
      inhibited by radical scavenger, catalase, and copper chelator. These results
      suggest that superoxide anion and H2O2 may generate from the glycation reaction
      of methylglyoxal with lysine and then Cu(2+) likely participates in a Fenton's
      type reaction to produce hydroxyl radicals, which may cause DNA cleavage. This
      mechanism may be linked to several diverse biological processes including
      mutagenesis, aging, carcinogenesis, and diabetic complications.

PMID- 14581170
TI  - Absence of tumor promoting activity of Euphorbia milii latex on the mouse back
      skin.
AB  - Euphorbia milii (Euphorbiaceae) is a decorative plant used in gardens and living
      fences. In China, it has also been employed in herbal remedies for hepatitis and
      abdominal edema. Since E. milii latex--lyophilized or in natura--proved to be a
      potent plant molluscicide, its toxicity to non-target organisms has been
      comprehensively studied. Concerns on a possible tumor promoting activity have
      discouraged its use as a locally-available alternative molluscicide in
      schistosomiasis control programs. Two in vitro assays (inhibition of metabolic
      cooperation in V79 cells and Epstein-Barr virus induction in Raji cells) had
      suggested that E. milii latex contained tumor-promoting substances. This study
      was undertaken to verify whether the latex acts as a tumor promoter in vivo as
      well. A single dose of the initiating agent DMBA (400 nmol) was applied on the
      back skin of male and female DBA/2 mice. Testing for tumor promoting activity
      began 10 days after initiation. Tetradecanoyl phorbol acetate (TPA) (5 nmol,
      positive control), lyophilized latex (20, 60 and 200 microg per mouse) or acetone
      (vehicle control) were applied on mouse back skin twice a week for 20 weeks. In
      TPA-treated mice, papillomas were firstly noted during the 11th week, and by the
      17th week all animals exhibited skin tumors. No tumors developed in mice treated
      with the solvent alone and in those exposed to latex. Findings from the present
      study therefore indicated that E. milii crude latex does not act as a tumor
      promoting agent on the mouse back skin assay.

PMID- 14581172
TI  - Increased airway responsiveness of a common fragrance component, 3-carene, after
      skin sensitisation--a study in isolated guinea pig lungs.
AB  - Lungs from skin-sensitised and non-sensitised guinea pigs were exposed via the
      airways to 3-carene (1900 mg/m3) and perfused with buffer containing either
      autologous plasma or lymphocytes. The experiments were performed in order to
      investigate the importance of blood components for the increased lung
      responsiveness seen in skin-sensitised animals. A reduction in lung function was
      noted in all lungs during 3-carene exposure. There was no difference in the 3
      carene response between lungs from skin-sensitised animals versus lungs from non
      sensitised animals when the perfusion buffer contained lymphocytes. However, when
      plasma diluted with buffer was used as perfusion medium, there was a significant
      enhancement in the response in lungs from sensitised versus lungs from non
      sensitised animals. This implies that skin sensitisation increases lung responses
      to inhaled 3-carene and those components in plasma, and not the lymphocyte
      fraction, contributes to the observed increased lung responsiveness.

PMID- 14581173
TI  - Bias induced by the use of creatinine-corrected values in evaluation of beta2
      microgloblin levels.
AB  - The present study was initiated to examine if the correction for creatinine (CR
      or cr) is the best approach among the three methods of correction for CR,
      correction for a specific gravity (SG or sg) and the use of observed values in
      managing difference in urine density. For this purpose, a database previously
      developed on 10,753 adult women in 10 non-polluted areas in Japan was re-visited
      for information on age, urinary levels of Cd, Mg, Ca, Zn, beta(2)-MG, and
      creatinine, and urine specific gravity as well as smoking habits. Never-smoking
      women with various urine density counted 8975 cases (the various urine density
      group). From these cases, 7081 cases with adequate urine density (i.e. 0.5 g/l <
      or = CR < or = 3.0 g/l and 1.010 < or = SG < or = 1.030) were selected (the
      adequate urine density group). When a beta(2)-MG level of 400 microg/g CR or 400
      microg/l was taken as a cut-off value for beta(2)-MG-uria, both the prevalence of
      beta(2)-MG(cr)-uria [i.e. cases with beta(2)-MG (as corrected for CR) in excess
      of 400 microg/g cr] and that of beta(2)-MG(sg)-uria increased as a function of
      the decrease in Cd(cr) or Cd(sg). The prevalence of beta(2)-MG(ob)-uria also
      varied as a function of CR and SG, especially of CR, but its range of variation
      was smaller than the corresponding changes in beta(2)-MG(cr)-uria prevalence. A
      noteworthy advantage for the use of observed values over that of SG-corrected
      values was the minimum effect of age. In over-all evaluation, therefore, the
      recommended approach appeared to be the use of non-corrected observed values
      (after selection of urine samples for adequate urine density if desired) or
      correction for SG, rather than correction for CR.

PMID- 14581174
TI  - Methyridine (2-[2-methoxyethyl]-pyridine]) and levamisole activate different ACh
      receptor subtypes in nematode parasites: a new lead for levamisole-resistance.
AB  - 1. The development of resistance to all chemotherapeutic agents increases and
      needs to be addressed. We are interested in resistance in parasitic nematodes to
      the anthelmintic levamisole. During studies on methyridine, we found that it gave
      us a new insight into pharmacological changes associated with levamisole
      resistance. Initially, electrophysiological investigation using a two
      micropipette current-clamp recording technique revealed that methyridine acts as
      a cholinergic agonist on nematode muscle receptors (Ascaris suum). Methyridine
      (>30 microm) produced reversible concentration-dependent depolarizations and
      increases in input conductance. Mecamylamine (30 microm) and paraherquamide (0.3
      microm) produced reversible antagonism of the depolarization and conductance
      responses to methyridine. These observations suggest that methyridine, like
      acetylcholine and levamisole, gates ion channels on the muscle of parasitic
      nematodes. 2. The antagonistic effects of dihydro-beta-erythroidine and
      paraherquamide on methyridine-induced contractions of A. suum muscle flaps were
      then examined to determine if methyridine showed subtype selectivity for N
      subtype (nicotine-sensitive) or L-subtype (levamisole-sensitive) acetylcholine
      receptors. Dihydro-beta-erythroidine weakly antagonized the effects of
      methyridine (but had no effect on levamisole responses). The antagonism of
      methyridine (pA2, 5.9) and nicotine (pA2, 6.1) by paraherquamide was similar, but
      was less than the antagonism of levamisole (pA2, 7.0). The antagonist profiles
      suggested that methyridine has a selective action on the N-subtype rather than on
      the L-subtype. 3. A novel use for a larval inhibition migration assay was made
      using L3 larvae of Oesophagostomum dentatum. Inhibitory effects of nicotine,
      levamisole, pyrantel and methyridine on the migration of larvae of levamisole
      sensitive (SENS) and levamisole-resistant (LEV-R) isolates were tested at
      different concentrations. Levamisole and pyrantel (putative L-subtype-selective
      agonists) concentration-response plots were displaced to the right in LEV-R
      isolates. Nicotine (an N-subtype-selective agonist) and methyridine produced
      little shift in concentration-response plots in the LEV-R isolates. Resistance
      dose ratios were used to calculate the relative selectivity, rhoL, for the L-type
      receptor (levamisole rhoL=1.0; pyrantel rhoL=0.93; methyridine rhoL=0.17;
      nicotine rhoL=0.06). These observations reveal an N-subtype-selective action of
      methyridine and suggest that levamisole resistance may be associated with a loss
      of the L-subtype, but not the N-subtype receptors. The pharmacology of
      methyridine suggests an approach for the treatment of levamisole-resistant
      parasites.

PMID- 14581175
TI  - ATP analogues with modified phosphate chains and their selectivity for rat P2X2
      and P2X2/3 receptors.
AB  - 1. Heteromeric P2X2/3 receptors are much more sensitive than homomeric P2X2
      receptors to alphabeta-methylene-ATP, and this ATP analogue is widely used to
      discriminate the two receptors on sensory neurons and other cells. 2. We sought
      to determine the structural basis for this selectivity by synthesising ADP and
      ATP analogues in which the alphabeta and/or betagamma oxygen atoms were replaced
      by other moieties (including -CH2-, -CHF-, -CHCl-, -CHBr-, -CF2-, -CCl2-, -CBr2-,
      -CHSO3-, -CHPO3-, -CFPO3-, -CClPO3-, -CH2-CH2-, C triple bond C, -NH-, -CHCOOH-).
      3. We tested their actions as agonists or antagonists by whole-cell recording
      from human embryonic kidney cells expressing P2X2 subunits alone (homomeric P2X2
      receptors), or cells expressing both P2X2 and P2X3 subunits, in which the current
      through heteromeric P2X2/3 receptors was isolated. 4. ADP analogues had no
      agonist or antagonist effect at either P2X2 or P2X2/3 receptors. All the ATP
      analogues tested were without agonist or antagonist activity at homomeric P2X2
      receptors, except betagamma-difluoromethylene-ATP, which was a weak agonist. 5.
      At P2X2/3 receptors, betagamma-imido-ATP, betagamma-methylene-ATP, and betagamma
      acetylene-ATP were weak agonists, whereas alphabeta,betagamma- and
      betagamma,gammadelta-bismethylene-AP4 were potent full agonists. betagamma
      Carboxymethylene-ATP and betagamma-chlorophosphonomethylene-ATP were weak
      antagonists at P2X2/3 receptors (IC50 about 10 microm). 6. The results indicate
      (a). that the homomeric P2X2 receptor presents very stringent structural
      requirements with respect to its activation by ATP; (b). that the heteromeric
      P2X2/3 receptor is much more tolerant of alphabeta and betagamma substitution;
      and (c). that a P2X2/3-selective antagonist can be obtained by introduction of
      additional negativity at the betagamma-methylene.

PMID- 14581176
TI  - Effects of insulin on vascular responses to spinal cord stimulation and
      vasoactive agents in pithed rats.
AB  - 1. Effects of insulin (2-600 pmol kg(-1) min(-1), i.v.) on vascular responses to
      spinal cord (lower thoracic vertebra, Th 9-12) stimulation (SCS) and to i.v.
      injection of noradrenaline (NA, 125-500 ng kg-1), angiotensin II (Ang II, 40-200
      pmol kg(-1), acetylcholine (ACh, 1 nmol kg(-1), calcitonin gene-related peptide
      (CGRP, 0.1 nmol kg(-1) and sodium nitroprusside (SNP, 5 microg kg-1) were
      examined in pithed rats. 2.In euglycemic pithed rats, low and medium doses of
      insulin dose-dependently potentiated vasopressor responses to SCS (2-8 Hz), NA,
      while higher doses of insulin had little effect on SCS- and NA-induced pressor
      responses. All doses of insulin significantly augmented pressor responses to Ang
      II. 3. In pithed rats with artificially increased blood pressure, SCS (2 and 4
      Hz) induced a frequency-dependent depressor response, which was blocked by
      infusion of CGRP(8-37) (CGRP receptor antagonist, 60 nmol kg(-1) min(-1). 4. In
      euglycemic pithed rats, low-doses of insulin significantly attenuated depressor
      responses to SCS and CGRP, but medium and high doses of insulin remained
      unaffected. 5. All doses of insulin significantly inhibited depressor response to
      ACh, while SNP-induced depressor response was not significantly affected by any
      doses of insulin. 6. These results suggest that insulin at low and medium
      concentrations increases adrenergic vasoconstriction, which is partly associated
      with inhibition of CGRPergic nerve function and endothelium function. It is also
      suggested that lack of insulin effect at higher concentrations may result from
      acute desensitization of insulin action, possibly via insulin receptors.

PMID- 14581177
TI  - Extended pharmacological profiles of rat P2Y2 and rat P2Y4 receptors and their
      sensitivity to extracellular H+ and Zn2+ ions.
AB  - 1. Two molecularly distinct rat P2Y receptors activated equally by adenosine-5'
      triphosphate (ATP) and uridine-5'-triphosphate (UTP) (rP2Y2 and rP2Y4 receptors)
      were expressed in Xenopus oocytes and studied extensively to find ways to
      pharmacologically distinguish one from the other. 2. Both P2Y subtypes were
      activated fully by a number of nucleotides. Tested nucleotides were equipotent at
      rP2Y4 (ATP=UTP=CTP=GTP=ITP), but not at rP2Y2 (ATP=UTP>CTP>GTP>ITP). For
      dinucleotides (ApnA, n=2-6), rP2Y4 was only fully activated by Ap4A, which was as
      potent as ATP. All tested dinucleotides, except for Ap2A, fully activated rP2Y2,
      but none were as potent as ATP. ATP gamma S and BzATP fully activated rP2Y2,
      whereas ATP gamma S was a weak agonist and BzATP was inactive (as an agonist) at
      rP2Y4 receptors. 3. Each P2Y subtype showed different sensitivities to known P2
      receptor antagonists. For rP2Y2, the potency order was suramin>>PPADS= RB-2>TNP
      ATP and suramin was a competitive antagonist (pA2, 5.40). For rP2Y4, the order
      was RB-2>>suramin>PPADS> TNP-ATP and RB-2 was a competitive antagonist (pA2,
      6.43). Also, BzATP was an antagonist at rP2Y4 receptors. 4. Extracellular
      acidification (from pH 8.0 to pH 5.5) enhanced the potency of ATP and UTP by 8-10
      fold at rP2Y4 but did not affect agonist responses at rP2Y2 receptors. 5.
      Extracellular Zn2+ ions (0.1-300 microM) coapplied with ATP inhibited agonist
      responses at rP2Y4 but not at rP2Y2 receptors. 6. These two P2Y receptors differ
      significantly in terms of agonist and antagonist profiles, and the modulatory
      activities of extracellular H+ and Zn2+ ions. These pharmacological differences
      will help to distinguish between rP2Y2 and rP2Y4 receptors, in vivo.

PMID- 14581178
TI  - T-1032, a cyclic GMP phosphodiesterase-5 inhibitor, acutely blocks physiologic
      insulin-mediated muscle haemodynamic effects and glucose uptake in vivo.
AB  - 1. Cyclic GMP phosphodiesterase-5 inhibitors have been shown to alter blood flow
      in specific tissues by potentiating local NO-dependent vasodilatory mechanisms.
      Since the haemodynamic effects of physiologic insulin, particularly capillary
      recruitment, may be critical for muscle glucose uptake in vivo and are blocked by
      inhibitors of nitric oxide synthase, we have explored the acute effects of the
      specific cGMP phosphodiesterase-5 inhibitor T-1032 on physiologic insulin action
      in anaesthetized healthy rats in vivo. 2. Whole-body glucose infusion (GIR),
      femoral blood flow (FBF), hind leg vascular resistance (VR), hind leg glucose
      uptake (HGU), 2-deoxyglucose uptake into muscles of the lower leg (R'g), hind leg
      metabolism of infused 1-methylxanthine (1-MX), a measure of capillary
      recruitment, and muscle cGMP were determined. The experimental groups were T-1032
      (10 microg min-1 kg-1) infused for 1 h before and during a euglycaemic insulin
      clamp (3 mU min-1 kg-1 x 2 h), T-1032 infused for 3 h with saline, T-1032 during
      a 2 h clamp, T-1032 with saline for 2 h, and a 2 h saline control. 3. Insulin
      increased GIR from zero to 13 mg min-1 kg-1, HGU from 0.1+/-0.01 to 0.43+/-0.05
      micromol min-1, R'g and 1-MX, marginally increased FBF, and had no effect on
      blood pressure or heart rate. T-1032 alone had no effect on blood pressure, heart
      rate, FBF, VR, HGU, R'g or 1-MX, but increased muscle cGMP. T-1032 1 h before and
      during insulin completely blocked GIR (1 h), HGU (2 h), R'g (2 h), and 1-MX (2
      h). T-1032 commenced with insulin had only partial blocking activity against
      insulin. 4. We conclude that T-1032 is a potent acutely acting inhibitor of the
      muscle effects of physiologic insulin on capillary recruitment and glucose uptake
      in vivo. These, together with inhibition of whole-body glucose infusion during
      insulin, may caution against the use of isoenzyme-5-specific cyclic GMP
      phosphodiesterase inhibitors as therapeutic agents.

PMID- 14581179
TI  - Decreased expression of glial cell line-derived neurotrophic factor signaling in
      rat models of neuropathic pain.
AB  - 1. In an attempt to clarify whether glial cell line-derived neurotrophic factor
      (GDNF), a survival factor for subpopulations of primary afferent neurons, is
      involved in the states of neuropathic pain, we observed changes in the
      expressions of GDNF and its signal-transducing receptor Ret after nerve injury in
      two rat models of neuropathic pain. 2. In the rats treated with sciatic nerve
      ligation (chronic constrictive injury (CCI) model) or spinal nerve ligation at L5
      (SNL model), the thresholds of paw withdrawal in response to mechanical or heat
      stimuli began to decrease on the injured side within the first week after the
      operation and the decreases in the thresholds persisted for more than 2 weeks. 3.
      In CCI-treated rats, the GDNF contents in L4 and L5 dorsal root ganglia (DRGs) on
      the injured side were markedly decreased at day 7 after the operation and stayed
      at low levels at day 14. In SNL-treated rats, comparable reductions of GDNF
      levels in L4 and L5 DRGs on the injured side were observed at 14 postoperative
      days. 4. Significant decreases of the percentages of DRG neurons expressing Ret
      were also observed at L4 DRGs in CCI-treated rats at 7 and 14 postoperative days
      and in SNL-treated rats at 14 days. 5. In CCI- or SNL-treated rats, continuous
      intrathecal administration of GDNF (12 microg day-1) using an osmotic pump
      suppressed the increased sensitivities to nociceptive stimuli to control levels.
      6. The present results suggested that the dysfunction of GDNF signaling in the
      nociceptive afferent system may contribute to the development and/or maintenance
      of neuropathic pain states.

PMID- 14581180
TI  - Rho kinase inhibitors block activation of pancreatic stellate cells.
AB  - 1. In response to pancreatic injury and in cell culture, pancreatic stellate
      cells (PSCs) are transformed ('activated') into highly proliferative
      myofibroblast-like cells, which express alpha-smooth muscle actin (alpha-SMA),
      and produce type I collagen and other extracellular matrix components. There is
      accumulating evidence that activated PSCs play important roles in pancreatic
      fibrosis and inflammation. 2. The small GTP-binding protein Rho has emerged as an
      important regulator of the actin cytoskeleton and cell morphology through the
      downstream effector Rho kinase (ROCK). But, the roles of Rho-ROCK pathway in PSCs
      are unknown. Here, we examined the effects of (+)-(R)-trans-4-(1-aminoethyl)-N-(4
      pyridyl) cyclohexanecarboxamide (Y-27632) and HA-1077 (fasudil), specific
      inhibitors of ROCK, on the activation of PSCs. 3. PSCs were isolated from the
      pancreas of male Wistar rats after perfusion with collagenase P. The actin
      cytoskeleton was analyzed by phalloidin staining. Expression of RhoA and ROCK was
      examined by immunostaining and Western blotting. Effects of Y-27632 and HA-1077
      on alpha-SMA expression, platelet-derived growth factor-induced proliferation and
      chemotaxis, and collagen production were assessed. 4. Culture-activated PSCs
      developed a well-spread cell shape, with extended stress fiber formation. PSCs
      expressed RhoA, ROCK-1, and ROCK-2. 5. Y-27632 caused disassembly of stress
      fibers. Y-27632 and HA-1077 inhibited alpha-SMA expression, proliferation,
      chemotaxis, and type I collagen production in culture-activated PSCs. 6. In
      addition, Y-27632 and HA-1077 inhibited spontaneous activation of freshly
      isolated PSCs in culture on plastic. 7. These findings suggest a role of Rho-ROCK
      pathway in the activation process of PSCs by regulating the actin cytoskeleton,
      and a potential application of Rho-ROCK pathway inhibitors for the treatment of
      pancreatic inflammation and fibrosis.

PMID- 14581182
TI  - TIR-FCS: staying on the surface can sometimes be better.

PMID- 14581181
TI  - Possible role of the protein kinase C/CPI-17 pathway in the augmented contraction
      of human myometrium after gestation.
AB  - 1. Activation of protein kinase C (PKC) by phorbol 12,13-dibutylate (PDBu, 1
      microm) induced sustained contractions with no increase in [Ca2+]i in nonpregnant
      and pregnant human myometria. The contractile effects of PDBu in pregnant
      myometrium were much greater than those in nonpregnant myometrium, and the
      contractions in pregnant myometrium were accompanied by an increase in myosin
      light chain (MLC) phosphorylation at Ser19. 2. The contraction induced by PDBu in
      pregnant myometrium was inhibited by the inhibitors of conventional PKC isoforms,
      bisindolylmaleimides and indolocarbazole, such as Go6976, Go6983, and Go6850 (1
      microM). LY333531 (1 microM), a specific inhibitor of PKC beta, also inhibited
      the PDBu-induced contraction in the pregnant myometrium. 3. In the pregnant
      myometrium permeabilized with alpha-toxin, PDBu increased the contractions
      induced at fixed Ca2+ concentration (0.3 microM) both in nonpregnant and pregnant
      myometria, indicating Ca2+ sensitization of contractile elements. 4. Western
      immunoblot analysis indicated that pregnant myometrium contained PKC isozymes
      such as conventional PKC (alpha, beta, gamma), novel PKC (delta, epsilon, theta),
      and atypical PKC (zeta but not iota and lambda). RT-PCR and real-time RT-PCR
      analysis indicated that, among the conventional PKC, the levels of mRNA of beta
      isoform in pregnant human myometrium were greater than those in nonpregnant
      myometrium. 5. CPI-17 is a substrate for PKC, and the phosphorylated CPI-17 is
      considered to inhibit myosin phosphatase. The levels of CPI-17 mRNA and protein
      expression were also greater in the pregnant myometrium. 6. These results suggest
      that the PKC-mediated contractile mechanism is augmented in human myometrium
      after gestation, and that this augmentation may be attributable to the increased
      activity of the beta PKC isoform and CPI-17.

PMID- 14581183
TI  - How thin can glass be? New ideas, new approaches.

PMID- 14581185
TI  - A molecular dynamics method for calculating molecular volume changes appropriate
      for biomolecular simulation.
AB  - Photothermal methods permit measurement of molecular volume changes of solvated
      molecules over nanosecond timescales. Such experiments are an important tool in
      investigating complex biophysical phenomena including identifying transient
      species in solution. Developing a microscopic understanding of the origin of
      volume changes in the condensed phase is needed to complement the experimental
      measurements. A molecular dynamics (MD) method exploiting available simulation
      methodology is demonstrated here that both mimics experimental measurements and
      provides microscopic resolution to the thermodynamic measurements. To calculate
      thermodynamic volume changes over time, isothermal-isobaric (NPT) MD is performed
      on a solution for a chosen length of time and the volume of the system is thus
      established. A further simulation is then performed by "plucking" out a solute
      molecule of interest to determine the volume of the system in its absence. The
      difference between these volumes is the thermodynamic volume of the solute
      molecule. NPT MD allows the volume of the system to fluctuate over time and this
      results in a statistical uncertainty in volumes that are calculated. It is found
      in the systems investigated here that simulations lasting a few nanoseconds can
      discern volume changes of approximately 1.0 ml/mole. This precision is comparable
      to that achieved empirically, making the experimental and theoretical techniques
      synergistic. The technique is demonstrated here on model systems including neat
      water, both charged and neutral aqueous methane, and an aqueous beta-sheet
      peptide.

PMID- 14581184
TI  - Potassium channel, ions, and water: simulation studies based on the high
      resolution X-ray structure of KcsA.
AB  - Interactions of Na(+), K(+), Rb(+), and Cs(+) ions within the selectivity filter
      of a potassium channel have been investigated via multiple molecular dynamics
      simulations (total simulation time, 48 ns) based on the high resolution structure
      of KcsA, embedded in a phospholipid bilayer. As in simulations based on a lower
      resolution structure of KcsA, concerted motions of ions and water within the
      filter are seen. Despite the use of a higher resolution structure and the
      inclusion of four buried water molecules thought to stabilize the filter, this
      region exhibits a significant degree of flexibility. In particular, pronounced
      distortion of filter occurs if no ions are present within it. The two most
      readily permeant ions, K(+) and Rb(+), are similar in their interactions with the
      selectivity filter. In contrast, Na(+) ions tend to distort the filter by binding
      to a ring of four carbonyl oxygens. The larger Cs(+) ions result in a small
      degree of expansion of the filter relative to the x-ray structure. Cs(+) ions
      also appear to interact differently with the gate region of the channel, showing
      some tendency to bind within a predominantly hydrophobic pocket. The four water
      molecules buried between the back of the selectivity filter and the remainder of
      the protein show comparable mobility to the surrounding protein and do not
      exchange with water molecules within the filter or the central cavity. A
      preliminary comparison of the use of particle mesh Ewald versus cutoff protocols
      for the treatment of long-range electrostatics suggests some difference in the
      kinetics of ion translocation within the filter.

PMID- 14581186
TI  - Enzyme-catalyzed gel proteolysis: an anomalous diffusion-controlled mechanism.
AB  - Enzyme-catalyzed proteolysis of gelatin gels has been studied. We report a gel
      degradation rate varying as the square of the enzyme concentration. The diffusion
      motion of enzymes in the gel has been measured by two-photon fluorescence
      correlation spectroscopy and identified as being anomalously slow. These
      experimental results are discussed from a theoretical point of view and
      interpreted in terms of a diffusion-controlled mechanism for the gel degradation.
      These results make a step toward the understanding of enzyme-catalyzed gel
      degradation and give new insight on biological processes such as the action of
      metalloproteinases in the extracellular matrix involved in cellular invasion.

PMID- 14581187
TI  - Prediction of reduction potential changes in rubredoxin: a molecular mechanics
      approach.
AB  - Predicting the effects of mutation on the reduction potential of proteins is
      crucial in understanding how reduction potentials are modulated by the protein
      environment. Previously, we proposed that an alanine vs. a valine at residue 44
      leads to a 50-mV difference in reduction potential found in homologous
      rubredoxins because of a shift in the polar backbone relative to the iron site
      due to the different side-chain sizes. Here, the aim is to determine the effects
      of mutations to glycine, isoleucine, and leucine at residue 44 on the structure
      and reduction potential of rubredoxin, and if the effects are proportional to
      side-chain size. Crystal structure analysis, molecular mechanics simulations, and
      experimental reduction potentials of wild-type and mutant Clostridium
      pasteurianum rubredoxin, along with sequence analysis of homologous rubredoxins,
      indicate that the backbone position relative to the redox site as well as solvent
      penetration near the redox site are both structural determinants of the reduction
      potential, although not proportionally to side-chain size. Thus, protein
      interactions are too complex to be predicted by simple relationships, indicating
      the utility of molecular mechanics methods in understanding them.

PMID- 14581188
TI  - Molecular simulation study of phospholipid bilayers and insights of the
      interactions with disaccharides.
AB  - Molecular simulations of hydrated dipalmitoylphosphatidylcholine lipid bilayers
      have been performed for temperatures in the range of 250-450 K. The area per
      headgroup increases with temperature from 58 to 77 A(2). Other properties such as
      hydration number, alkyl tail order parameter, diffusion coefficients, and radial
      distribution functions exhibit a clear dependence on temperature. Simulations of
      bilayers have also been performed in the presence of two disaccharides, namely
      trehalose and sucrose, at concentrations of up to 18 wt % (lipid-free basis). The
      simulated area per headgroup of the bilayer is not affected by the presence of
      the disaccharides, suggesting that the overall structure of the bilayer remains
      undisturbed. The results of simulations reveal that the interaction of
      disaccharide molecules with the bilayer occurs at the surface of the bilayer, and
      it is governed by the formation of multiple hydrogen bonds to specific groups of
      the lipid. Disaccharide molecules are observed to adopt specific conformations to
      fit onto the surface topology of the bilayer, often interacting with up to three
      different lipids simultaneously. At high disaccharide concentrations, the results
      of simulations indicate that disaccharides can serve as an effective replacement
      for water under anhydrous conditions, which helps explain their effectiveness as
      lyophilization agents for liposomes and cells.

PMID- 14581190
TI  - Electrostatic model of S4 motion in voltage-gated ion channels.
AB  - The S4 transmembrane domain of the family of voltage-gated ion channels is
      generally thought to be the voltage sensor, whose translocation by an applied
      electric field produces the gating current. Experiments on hSkMI Na(+) channels
      and both Shaker and EAG K(+) channels indicate which S4 residues cross the
      membrane-solution interface during activation gating. Using this structural
      information, we derive the steady-state properties of gating-charge transfer for
      wild-type and mutant Shaker K(+) channels. Assuming that the energetics of gating
      is dominated by electrostatic forces between S4 charges and countercharges on
      neighboring transmembrane domains, we calculate the total energy as a function of
      transmembrane displacement and twist of the S4 domain. The resulting
      electrostatic energy surface exhibits a series of deep energy minima,
      corresponding to the transition states of the gating process. The steady-state
      gating-charge distribution is then given by a Boltzmann distribution among the
      transition states. The resulting gating-charge distributions are compared to
      experimental results on wild-type and charge-neutralized mutants of the Shaker
      K(+) channel.

PMID- 14581189
TI  - Conferring thermostability to mesophilic proteins through optimized electrostatic
      surfaces.
AB  - Recently, there have been several experimental reports of proteins displaying
      appreciable stability gains through mutation of one or two amino acid residues.
      Here, we employ a simple theoretical model to quickly screen mutant structures
      for increased thermostability through optimization of the protein's electrostatic
      surface. Our results are able to reproduce the experimental observation that
      elimination of like-charge repulsions and creation of opposite-charge attractions
      on the protein surface is an efficient method to confer thermostability to a
      mesophilic protein. Using Poisson-Boltzmann electrostatics, we calculate relative
      protein stabilities for the exhaustive surface mutagenesis of the cold shock,
      RNase T1, and CheY proteins. Comparison with 25 experimentally characterized cold
      shock protein mutants reveals an average correlation of 0.86. The model is also
      quantitatively accurate when reproducing the experimental D49A and D49H mutant
      stabilities of RNase T1. This work represents the first comprehensive in silico
      screening of mutant candidates likely to confer thermostability to mesophilic
      proteins through optimization of surface electrostatics. Systematic single
      mutant, followed by double mutant, screening yields a limited number of mutant
      structures displaying significant stability gains suitable for subsequent
      experimental characterization.

PMID- 14581191
TI  - Molecular dynamics simulation of protein folding by essential dynamics sampling:
      folding landscape of horse heart cytochrome c.
AB  - A new method for simulating the folding process of a protein is reported. The
      method is based on the essential dynamics sampling technique. In essential
      dynamics sampling, a usual molecular dynamics simulation is performed, but only
      those steps, not increasing the distance from a target structure, are accepted.
      The distance is calculated in a configurational subspace defined by a set of
      generalized coordinates obtained by an essential dynamics analysis of an
      equilibrated trajectory. The method was applied to the folding process of horse
      heart cytochrome c, a protein with approximately 3000 degrees of freedom.
      Starting from structures, with a root-mean-square deviation of approximately 20 A
      from the crystal structure, the correct folding was obtained, by utilizing only
      106 generalized degrees of freedom, chosen among those accounting for the
      backbone carbon atoms motions, hence not containing any information on the side
      chains. The folding pathways found are in agreement with experimental data on the
      same molecule.

PMID- 14581192
TI  - DNA basepair step deformability inferred from molecular dynamics simulations.
AB  - The sequence-dependent DNA deformability at the basepair step level was
      investigated using large-scale atomic resolution molecular dynamics simulation of
      two 18-bp DNA oligomers: d(GCCTATAAACGCCTATAA) and d(CTAGGTGGATGACTCATT). From an
      analysis of the structural fluctuations, the harmonic potential energy functions
      for all 10 unique steps with respect to the six step parameters have been
      evaluated. In the case of roll, three distinct groups of steps have been
      identified: the flexible pyrimidine-purine (YR) steps, intermediate purine-purine
      (RR), and stiff purine-pyrimidine (RY). The YR steps appear to be the most
      flexible in tilt and partially in twist. Increasing stiffness from YR through RR
      to RY was observed for rise, whereas shift and slide lack simple trends. A
      proposed measure of the relative importance of couplings identifies the slide
      rise, twist-roll, and twist-slide couplings to play a major role. The force
      constants obtained are of similar magnitudes to those based on a crystallographic
      ensemble. However, the current data have a less complicated and less pronounced
      sequence dependence. A correlation analysis reveals concerted motions of
      neighboring steps and thus exposes limitations in the dinucleotide model. The
      comparison of DNA deformability from this and other studies with recent quantum
      chemical stacking energy calculations suggests poor correlation between the
      stacking and flexibility.

PMID- 14581193
TI  - Electrostatic tuning of permeation and selectivity in aquaporin water channels.
AB  - Water permeation and electrostatic interactions between water and channel are
      investigated in the Escherichia coli glycerol uptake facilitator GlpF, a member
      of the aquaporin water channel family, by molecular dynamics simulations. A
      tetrameric model of the channel embedded in a 16:0/18:1c9
      palmitoyloleylphosphatidylethanolamine membrane was used for the simulations.
      During the simulations, water molecules pass through the channel in single file.
      The movement of the single file water molecules through the channel is concerted,
      and we show that it can be described by a continuous-time random-walk model. The
      integrity of the single file remains intact during the permeation, indicating
      that a disrupted water chain is unlikely to be the mechanism of proton exclusion
      in aquaporins. Specific hydrogen bonds between permeating water and protein at
      the channel center (at two conserved Asp-Pro-Ala "NPA" motifs), together with the
      protein electrostatic fields enforce a bipolar water configuration inside the
      channel with dipole inversion at the NPA motifs. At the NPA motifs water-protein
      electrostatic interactions facilitate this inversion. Furthermore, water-water
      electrostatic interactions are in all regions inside the channel stronger than
      water-protein interactions, except near a conserved, positively charged Arg
      residue. We find that variations of the protein electrostatic field through the
      channel, owing to preserved structural features, completely explain the bipolar
      orientation of water. This orientation persists despite water translocation in
      single file and blocks proton transport. Furthermore, we find that for permeation
      of a cation, ion-protein electrostatic interactions are more unfavorable at the
      conserved NPA motifs than at the conserved Arg, suggesting that the major barrier
      against proton transport in aquaporins is faced at the NPA motifs.

PMID- 14581195
TI  - Atomically detailed simulations of helix formation with the stochastic difference
      equation.
AB  - An algorithm is described to compute approximate classical trajectories as a
      boundary value problem with an integration step in the arc length. High-frequency
      motions are filtered out when a large integration step is used, maintaining the
      stability of the algorithm. At the limit of high filtering (large steps), but
      still offering an accurate description of the continuous path, the trajectory
      approaches the steepest descent path (SDP). The steepest descent path is widely
      used as a reaction coordinate in chemical systems. At intermediate step sizes,
      some inertial motions remain, interpolating between reaction coordinates and
      exact classical trajectories. Numerical studies of spatial and energetic
      properties of meta-trajectories are carried out. Two systems are considered here:
      valine dipeptide and the folding of a small helical protein. Although
      thermodynamic properties of meta-trajectories are affected by the filtering, the
      ordering of events remains similar for substantial differences in trajectory
      resolution.

PMID- 14581194
TI  - An implicit membrane generalized born theory for the study of structure,
      stability, and interactions of membrane proteins.
AB  - Exploiting recent developments in generalized Born (GB) electrostatics theory, we
      have reformulated the calculation of the self-electrostatic solvation energy to
      account for the influence of biological membranes. Consistent with continuum
      Poisson-Boltzmann (PB) electrostatics, the membrane is approximated as an solvent
      inaccessible infinite planar low-dielectric slab. The present membrane GB model
      closely reproduces the PB electrostatic solvation energy profile across the
      membrane. The nonpolar contribution to the solvation energy is taken to be
      proportional to the solvent-exposed surface area (SA) with a phenomenological
      surface tension coefficient. The proposed membrane GB/SA model requires minor
      modifications of the pre-existing GB model and appears to be quite efficient. By
      combining this implicit model for the solvent/bilayer environment with advanced
      computational sampling methods, like replica-exchange molecular dynamics, we are
      able to fold and assemble helical membrane peptides. We examine the reliability
      of this model and approach by applications to three membrane peptides: melittin
      from bee venom, the transmembrane domain of the M2 protein from Influenza A (M2
      TMP), and the transmembrane domain of glycophorin A (GpA). In the context of
      these proteins, we explore the role of biological membranes (represented as a low
      dielectric medium) in affecting the conformational changes in melittin, the tilt
      of transmembrane peptides with respect to the membrane normal (M2-TMP), helix-to
      helix interactions in membranes (GpA), and the prediction of the configuration of
      transmembrane helical bundles (GpA). The present method is found to perform well
      in each of these cases and is anticipated to be useful in the study of folding
      and assembly of membrane proteins as well as in structure refinement and modeling
      of membrane proteins where a limited number of experimental observables are
      available.

PMID- 14581196
TI  - A mesoscopic model for protein-protein interactions in solution.
AB  - Protein self-association may be detrimental in biological systems, but can be
      utilized in a controlled fashion for protein crystallization. It is hence of
      considerable interest to understand how factors like solution conditions prevent
      or promote aggregation. Here we present a computational model describing
      interactions between protein molecules in solution. The calculations are based on
      a molecular description capturing the detailed structure of the protein molecule
      using x-ray or nuclear magnetic resonance structural data. Both electrostatic and
      van der Waals interactions are included and the salt particles are explicitly
      treated allowing investigations of systems containing mono-, di-, and trivalent
      ions. For three different proteins-lysozyme, alpha-chymotrypsinogen, and
      calbindin D(9k)-we have investigated under which conditions (salt concentration,
      ion valency, pH, and/or solvent) the proteins are expected to aggregate via
      evaluation of the second virial coefficient. Good agreement is found with
      experimental data where available. Calbindin is investigated in more detail, and
      it is demonstrated how changes in solvent and/or counterion valency lead to
      attractive ion-ion correlation effects. For high valency counterions we have
      found abnormal trends in the second virial coefficient. With trivalent
      counterions, attraction of two negatively charged protein molecules can be
      favored because the repulsive term is decreased for entropic reasons due to the
      low number of particles present.

PMID- 14581197
TI  - The universal dynamics of tumor growth.
AB  - Scaling techniques were used to analyze the fractal nature of colonies of 15 cell
      lines growing in vitro as well as of 16 types of tumor developing in vivo. All
      cell colonies were found to exhibit exactly the same growth dynamics-which
      correspond to the molecular beam epitaxy (MBE) universality class. MBE dynamics
      are characterized by 1), a linear growth rate, 2), the constraint of cell
      proliferation to the colony/tumor border, and 3), surface diffusion of cells at
      the growing edge. These characteristics were experimentally verified in the
      studied colonies. That these should show MBE dynamics is in strong contrast with
      the currently established concept of tumor growth: the kinetics of this type of
      proliferation rules out exponential or Gompertzian growth. Rather, a clear linear
      growth regime is followed. The importance of new cell movements-cell diffusion at
      the tumor border-lies in the fact that tumor growth must be conceived as a
      competition for space between the tumor and the host, and not for nutrients or
      other factors. Strong experimental evidence is presented for 16 types of tumor,
      the growth of which cell surface diffusion may be the main mechanism responsible
      in vivo. These results explain most of the clinical and biological features of
      colonies and tumors, offer new theoretical frameworks, and challenge the wisdom
      of some current clinical strategies.

PMID- 14581198
TI  - Protein evolution within a structural space.
AB  - Understanding of the evolutionary origins of protein structures represents a key
      component of the understanding of molecular evolution as a whole. Here we seek to
      elucidate how the features of an underlying protein structural "space" might
      impact protein structural evolution. We approach this question using lattice
      polymers as a completely characterized model of this space. We develop a measure
      of structural comparison of lattice structures that is analogous to the one used
      to understand structural similarities between real proteins. We use this measure
      of structural relatedness to create a graph of lattice structures and compare
      this graph (in which nodes are lattice structures and edges are defined using
      structural similarity) to the graph obtained for real protein structures. We find
      that the graph obtained from all compact lattice structures exhibits a
      distribution of structural neighbors per node consistent with a random graph. We
      also find that subgraphs of 3500 nodes chosen either at random or according to
      physical constraints also represent random graphs. We develop a divergent
      evolution model based on the lattice space which produces graphs that, within
      certain parameter regimes, recapitulate the scale-free behavior observed in
      similar graphs of real protein structures.

PMID- 14581199
TI  - Unbiased rotational moves for rigid-body dynamics.
AB  - We introduce an unbiased protocol for performing rotational moves in rigid-body
      dynamics simulations. This approach-based on the analytic solution for the
      rotational equations of motion for an orthogonal coordinate system at constant
      angular velocity-removes deficiencies that have been largely ignored in Brownian
      dynamics simulations, namely errors for finite rotations that result from
      applying the noncommuting rotational matrices in an arbitrary order. Our
      algorithm should thus replace standard approaches to rotate local coordinate
      frames in Langevin and Brownian dynamics simulations.

PMID- 14581200
TI  - Glycerol conductance and physical asymmetry of the Escherichia coli glycerol
      facilitator GlpF.
AB  - The aquaglyceroporin GlpF is a transmembrane channel of Escherichia coli that
      facilitates the uptake of glycerol by the cell. Its high glycerol uptake rate is
      crucial for the cell to survive in very low glycerol concentrations. Although
      GlpF allows both influx and outflux of glycerol, its structure, similar to the
      structure of maltoporin, exhibits a significant degree of asymmetry. The
      potential of mean force characterizing glycerol in the channel shows a
      corresponding asymmetry with an attractive vestibule only at the periplasmic
      side. In this study, we analyze the potential of mean force, showing that a
      simplified six-step model captures the kinetics and yields a glycerol conduction
      rate that agrees well with observation. The vestibule improves the conduction
      rate by 40% and 75% at 10- micro M and 10-mM periplasmic glycerol concentrations,
      respectively. In addition, neither the conduction rate nor the conduction
      probability for a single glycerol (efficiency) depends on the orientation of
      GlpF. GlpF appears to conduct equally well in both directions under physiological
      conditions.

PMID- 14581202
TI  - Asymmetric structural motions of the homomeric alpha7 nicotinic receptor ligand
      binding domain revealed by molecular dynamics simulation.
AB  - A homology model of the ligand binding domain of the alpha7 nicotinic receptor is
      constructed based on the acetylcholine-binding protein crystal structure. This
      structure is refined in a 10 ns molecular dynamics simulation. The modeled
      structure proves fairly resilient, with no significant changes at the secondary
      or tertiary structural levels. The hypothesis that the acetylcholine-binding
      protein template is in the activated or desensitized state, and the absence of a
      bound agonist in the simulation suggests that the structure may also be relaxing
      from this state to the activatable state. Candidate motions that take place
      involve not only the side chains of residues lining the binding sites, but also
      the subunit positions that determine the overall shape of the receptor. In
      particular, two nonadjacent subunits move outward, whereas their partners
      counterclockwise to them move inward, leading to a marginally wider interface
      between themselves and an overall asymmetric structure. This in turn affects the
      binding sites, producing two that are more open and characterized by distinct
      side-chain conformations of W54 and L118, although motions of the side chains of
      all residues in every binding site still contribute to a reduction in binding
      site size, especially the outward motion of W148, which hinders acetylcholine
      binding. The Cys loop at the membrane interface also displays some flexibility.
      Although the short simulation timescale is unlikely to sample adequately all the
      conformational states, the pattern of observed motions suggests how ligand
      binding may correlate with larger-scale subunit motions that would connect with
      the transmembrane region that controls the passage of ions. Furthermore, the
      shape of the asymmetry with binding sites of differing affinity for
      acetylcholine, characteristic of other nicotinic receptors, may be a natural
      property of the relaxed, activatable state of alpha7.

PMID- 14581201
TI  - Thermodynamics of heat activation of single capsaicin ion channels VR1.
AB  - Temperature affects functions of all ion channels, but few of them can be gated
      directly. The vanilloid receptor VR1 provides one exception. As a pain receptor,
      it is activated by heat >42 degrees C in addition to other noxious stimuli, e.g.
      acids and vanilloids. Although it is understood how ligand- and voltage-gated
      channels might detect their stimuli, little is known on how heat could be sensed
      and activate a channel. In this study, we characterized the heat-induced single
      channel activity of VR1, in an attempt to localize the temperature-dependent
      components involved in the activation of the channel. At <42 degrees C, openings
      were few and brief. Raising the ambient temperature rapidly increased the
      frequency of openings. Despite the large temperature coefficient of the apparent
      activity (Q(10) approximately 27), the unitary current, the open dwell-times, and
      the intraburst closures were all only weakly temperature dependent (Q(10) < 2).
      Instead, heat had a localized effect on the reduction of long closures between
      bursts (Q(10) approximately 7) and the elongation of burst durations (Q(10)
      approximately 32). Both membrane lipids and solution ionic strength affected the
      temperature threshold of the activation, but neither diminished the response. The
      thermodynamic basis of heat activation is discussed, to elucidate what makes a
      thermal-sensitive channel unique.

PMID- 14581203
TI  - Kinetic diversity of single-channel burst openings underlying persistent Na(+)
      current in entorhinal cortex neurons.
AB  - The kinetic diversity of burst openings responsible for the persistent Na(+)
      current (I(NaP)) in entorhinal cortex neurons was examined by separately
      analyzing single bursts. Although remarkable kinetic variability was observed
      among bursts in terms of intraburst opening probability and mean open and closed
      times, the values of time constants describing intraburst open times (tau(o(b))s)
      and closed times (tau(c(b))s) were distributed around well-defined peaks. At -40
      mV, tau(o(b)) peaks were found at approximately 0.34 (tau(o(b))1) and 0.77
      (tau(o(b))2) ms, and major tau(c(b)) peaks were found at approximately 0.24
      (tau(c(b))1) and 0.54 (tau(c(b))2) ms. In approximately 80% of the bursts two
      preferential gating modes were found that consisted of a combination of either
      tau(o(b))1 and tau(c(b))2 ("intraburst mode 1"), or tau(o(b))2 and tau(c(b))1
      ("intraburst mode 2"). Individual channels could switch between different gating
      modalities, but normally tended to maintain a specific gating mode for long
      periods. Mean burst duration also displayed considerable variability. At least
      three time constants were found to describe burst duration, and the frequencies
      at which each of the corresponding "bursting states" occurred varied in different
      channels. Short-lasting bursting states were preferentially associated with
      intraburst mode 1, whereas very-long-lasting bursts tended to gate according to
      mode 2 only or other modes that included considerably longer mean open times.
      These results show that I(NaP) channels can generate multiple intraburst open and
      closed states and bursting states, but these different kinetic states tend to
      combine in definite ways to produce a limited number of prevalent, well-defined
      gating modalities. Modulation of distinct gating modalities in individual Na(+)
      channels may be a powerful form of plasticity to influence neuronal excitability
      and function.

PMID- 14581204
TI  - Pathways of lipid vesicle deposition on solid surfaces: a combined QCM-D and AFM
      study.
AB  - Supported lipid bilayers (SLBs) are popular models of cell membranes with
      potential biotechnological applications, yet the mechanism of SLB formation is
      only partially understood. In this study, the adsorption and subsequent
      conformational changes of sonicated unilamellar vesicles on silica supports were
      investigated by quartz crystal microbalance with dissipation monitoring and
      atomic force microscopy, using mixtures of zwitterionic, negatively charged, and
      positively charged lipids, both in the presence and in the absence of Ca(2+)
      ions. Four different pathways of vesicle deposition could be distinguished.
      Depending on their charge, vesicles i). did not adsorb; ii). formed a stable
      vesicular layer; or iii). decomposed into an SLB after adsorption at high
      critical coverage or iv). at low coverage. Calcium was shown to enhance the
      tendency of SLB formation for negatively charged and zwitterionic vesicles. The
      role of vesicle-support, interbilayer, and intrabilayer interactions in the
      formation of SLBs is discussed.

PMID- 14581205
TI  - Metastability of a supercompressed fluid monolayer.
AB  - Previous studies showed that monomolecular films of extracted calf surfactant
      collapse at the equilibrium spreading pressure during quasi-static compressions
      but become metastable at much higher surface pressures when compressed faster
      than a threshold rate. To determine the mechanism by which the films become
      metastable, we studied single-component films of 1-palmitoyl-2-oleoyl
      phosphatidylcholine (POPC). Initial experiments confirmed similar metastability
      of POPC if compressed above a threshold rate. Measurements at different surface
      pressures then showed that rates of collapse, although initially increasing above
      the equilibrium spreading pressure, reached a sharply defined maximum and then
      slowed considerably. When heated, rapidly compressed films recovered their
      ability to collapse with no discontinuous change in area, arguing that the
      metastability does not reflect transition of the POPC film to a new phase. These
      observations indicate that in several respects, the supercompression of POPC
      monolayers resembles the supercooling of three-dimensional liquids toward a glass
      transition.

PMID- 14581206
TI  - The effect of fructan on the phospholipid organization in the dry state.
AB  - Fructans, a family of oligo- and polyfructoses, are implicated to play a drought
      protecting role in plants. Inulin-type fructan is able to preserve the membrane
      barrier during dehydration. However, whether other fructans would be able to
      perform this function is unknown. In addition, almost nothing is known about the
      organization of these systems, which could give insight into the protective
      mechanism. To get insight into these questions the effect of different fructans
      on phosphatidylcholine-based model systems under conditions of dehydration was
      analyzed. Using a vesicle leakage assay, it was found that both levan- and inulin
      type fructans protected the membrane barrier. This suggests that fructans in
      general would be able to protect the membrane barrier function. Furthermore, both
      fructan-types inhibited vesicle fusion to a large extent as measured using a
      lipid-mixing assay. Using x-ray diffraction, it was found that in the presence of
      both inulin- and levan-type fructans the lamellar repeat distance increased
      considerably. From this it was concluded that fructans are present between the
      lipid bilayers during drying. Furthermore, they stabilize the L(alpha) phase. In
      contrast to fructans, dextran did not increase the lamellar repeat distance and
      it even promoted L(beta) phase formation. These data support the hypothesis that
      fructans can have a membrane-protecting role during dehydration, and give insight
      into the mechanism of protection.

PMID- 14581207
TI  - Creating biological membranes on the micron scale: forming patterned lipid
      bilayers using a polymer lift-off technique.
AB  - We present a new method for creating patches of fluid lipid bilayers with
      conjugated biotin and other compounds down to 1 microm resolution using a
      photolithographically patterned polymer lift-off technique. The patterns are
      realized as the polymer is mechanically peeled away in one contiguous piece in
      solution. The functionality of these surfaces is verified with binding of
      antibodies and avidin on these uniform micron-scale platforms. The biomaterial
      patches, measuring 1 micro m-76 microm on edge, provide a synthetic biological
      substrate for biochemical analysis that is approximately 100x smaller in width
      than commercial printing technologies. 100 nm unilamellar lipid vesicles spread
      to form a supported fluid lipid bilayer on oxidized silicon surface as confirmed
      by fluorescence photobleaching recovery. Fluorescence photobleaching recovery
      measurements of DiI (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine
      perchlorate (DiIC(18)(3))) stained bilayer patches yielded an average diffusion
      coefficient of 7.54 +/- 1.25 microm(2) s(-1), equal to or slightly faster than
      typically found in DiI stained cells. This diffusion rate is approximately 3x
      faster than previous values for bilayers on glass. This method provides a new
      means to form functionalized fluid lipid bilayers as micron-scale platforms to
      immobilize biomaterials, capture antibodies and biotinylated reagents from
      solution, and form antigenic stimuli for cell stimulation.

PMID- 14581208
TI  - Separation of liquid phases in giant vesicles of ternary mixtures of
      phospholipids and cholesterol.
AB  - We use fluorescence microscopy to directly observe liquid phases in giant
      unilamellar vesicles. We find that a long list of ternary mixtures of high
      melting temperature (saturated) lipids, low melting temperature (usually
      unsaturated) lipids, and cholesterol produce liquid domains. For one model
      mixture in particular, DPPC/DOPC/Chol, we have mapped phase boundaries for the
      full ternary system. For this mixture we observe two coexisting liquid phases
      over a wide range of lipid composition and temperature, with one phase rich in
      the unsaturated lipid and the other rich in the saturated lipid and cholesterol.
      We find a simple relationship between chain melting temperature and miscibility
      transition temperature that holds for both phosphatidylcholine and sphingomyelin
      lipids. We experimentally cross miscibility boundaries both by changing
      temperature and by the depletion of cholesterol with beta-cyclodextrin. Liquid
      domains in vesicles exhibit interesting behavior: they collide and coalesce, can
      finger into stripes, and can bulge out of the vesicle. To date, we have not
      observed macroscopic separation of liquid phases in only binary lipid mixtures.

PMID- 14581209
TI  - Detergents destabilize the cubic phase of monoolein: implications for membrane
      protein crystallization.
AB  - The in meso method for membrane protein crystallization uses a lipidic cubic
      phase as the hosting medium. The cubic phase provides a lipid bilayer into which
      the protein presumably reconstitutes and from which protein crystals nucleate and
      grow. The solutions used to spontaneously form the protein-enriched cubic phase
      often contain significant amounts of detergents that were employed initially to
      purify and to solubilize the membrane protein. By virtue of their surface
      activity, detergents have the potential to impact on the phase properties of the
      in meso system and, by extension, the outcome of the crystallization process. The
      purpose of this study was to quantify the effects that a popular series of
      nonionic detergents, the n-alkyl-beta-D-glucopyranosides, have on the phase
      behavior of hydrated monoolein, the lipid upon which the in meso method is based.
      Phase identity and phase microstructure were characterized by small-angle x-ray
      diffraction on samples prepared to mimic in meso crystallization conditions.
      Measurements were made in the 0-40 degrees C range. Samples prepared in the
      cooling direction allow for the expression of metastability, a feature of liquid
      crystalline phases that might be exploited in low-temperature crystallization.
      The results show that the cubic phase is relatively insensitive to small amounts
      of alkyl glucosides. However, at higher levels the detergents trigger a
      transition to the lamellar phase in a temperature- and salt concentration
      dependent manner. These effects have important implications for in meso
      crystallization. A diffraction-based method for assaying detergents is presented.

PMID- 14581210
TI  - Effect of detergents on the association of the glycophorin a transmembrane helix.
AB  - We have examined the role of the environment on the interactions between
      transmembrane helices using, as a model system, the dimerization of the
      glycophorin A transmembrane helix. In this study we have focused on micellar
      environments and have examined a series of detergents that include a range of
      alkyl chain lengths, combined with ionic, zwitterionic, and nonionic headgroups.
      For each we have measured how the apparent equilibrium constant depends on the
      detergent concentration. In two detergents we also measured the thermal
      sensitivity of the equilibrium constant, from which we derive the van't Hoff
      enthalpy and entropy. We show that several simple models are inadequate for
      explaining our results; however, models that include the effect of detergent
      concentration on detergent binding are able to account for our measurements. Our
      analysis suggests that the effects of detergents on helix association are due to
      a pair of opposing effects: an enthalpic effect, which drives association as the
      detergent concentration is increased and which is sensitive to the chemical
      nature of the detergent headgroup, opposed by an entropic effect, which drives
      peptide dissociation as the detergent concentration is raised. Our results also
      indicate that the monomer-monomer interface is relatively hydrophilic and that
      association within detergent micelles is driven by the enthalpy change. The wide
      variations in glycophorin a dimmer, stability with the detergent used, together
      with the realization that this results from the balance between two opposing
      effects, suggests that detergents might be selected that drive association rather
      than dissociation of peptide dimers.

PMID- 14581211
TI  - Characterization of DNA/lipid complexes by fluorescence resonance energy
      transfer.
AB  - Fluorescence resonance energy transfer (FRET) is a potential method for the
      characterization of DNA-cationic lipid complexes (lipoplexes). In this work, we
      used FRET models assuming a multilamellar lipoplex arrangement. The application
      of these models allows the determination of the distance between the fluorescent
      intercalator on the DNA and a membrane dye on the lipid, and/or the evaluation of
      encapsulation efficiencies of this liposomal vehicle. The experiments were
      carried out in 1,2-dioleoyl-3-trimethylammonium-propane/pUC19 complexes with
      different charge ratios. We used 2-(3-(diphenylhexatrienyl)propanoyl)-1
      hexadecanoyl-sn-glycero-3-phosphocholine (DPH-PC) and 2-(4,4-difluoro-5-octyl-4
      bora-3a,4a-diaza-s-indacene-3-pentanoyl)-1-hexadecanoyl-sn-glycero-3
      phosphocholine (BODIPY-PC) as membrane dyes, and ethidium bromide (EtBr) and BOBO
      1 as DNA intercalators. In cationic complexes (charge ratios (+/-) >or= 2), we
      verified that BOBO-1 remains bound to DNA, and FRET occurs to the membrane dye.
      This was also confirmed by anisotropy and lifetime measurements. In complexes
      with all DNA bound to the lipid (charge ratio (+/-) = 4), we determined 27 A as
      the distance between the donor and acceptor planes (half the repeat distance for
      a multilamellar arrangement). In complexes with DNA unbound to the lipids (charge
      ratio (+/-) = 0.5 and 2), we calculated the encapsulation efficiencies. The
      presented FRET methodology is, to our knowledge, the first procedure allowing
      quantification of lipid-DNA contact.

PMID- 14581212
TI  - Mixed bilayer containing dipalmitoylphosphatidylcholine and
      dipalmitoylphosphatidylserine: lipid complexation, ion binding, and
      electrostatics.
AB  - Two mixed bilayers containing dipalmitoylphosphatidylcholine and
      dipalmitoylphosphatidylserine at a ratio of 5:1 are simulated in NaCl electrolyte
      solutions of different concentration using the molecular dynamics technique.
      Direct NH.O and CH.O hydrogen bonding between lipids was observed to serve as the
      basis of interlipid complexation. It is deduced from our results and previous
      studies that dipalmitoylphosphatidylcholine alone is less likely to form
      interlipid complexes than in the presence of bound ions or other bilayer
      "impurities" such as dipalmitoylphosphatidylserine. The binding of counterions is
      observed and quantitated. Based upon the calculated ion binding constants, the
      Gouy-Chapman surface potential (theta) is calculated. In addition we calculated
      the electrostatic potential profile (Phi) by twice integrating the system charge
      distribution. A large discrepancy between and the value of Phi at the membrane
      surface is observed. However, at "larger" distance from the bilayer surface, a
      qualitative similarity in the z-profiles of Phi and psi(GC) is seen. The
      discrepancy between the two potential profiles near the bilayer surface is
      attributed to the discrete and nonbulk-like nature of water in the interfacial
      region and to the complex geometry of this region.

PMID- 14581213
TI  - At physiological temperatures the ATPase rates of shortening soleus and psoas
      myofibrils are similar.
AB  - We obtained the temperature dependences of the adenosine triphosphatase (ATPase)
      activities (calcium-activated and relaxed) of myofibrils from a slow muscle,
      which we compared with those from a fast muscle. We chose rabbit soleus and psoas
      because their myosin heavy chains are almost pure: isoforms I and IIX,
      respectively. The Arrhenius plots of the ATPases are linear (4-35 degrees C) with
      energies of activation for soleus myofibrils 155 kJ mol(-1) (activated) and 78 kJ
      mol(-1) (relaxed). With psoas myofibrils, the energies of activation were 71 kJ
      mol(-1) (activated) and 60 kJ mol(-1) (relaxed). When extrapolated to 42 degrees
      C the ATPase rates of the two types of myofibril were identical: 50 s(-1)
      (activated) and 0.23 s(-1) (relaxed). Whereas with psoas myofibrils the K(m) for
      adenosine triphosphate (activated ATPase) is relatively insensitive to
      temperature, that for soleus myofibrils increased from 0.3 microM at 4 degrees C
      to 66.5 microM at 35 degrees C. Our results illustrate the importance of
      temperature when comparing the mechanochemical coupling in different types of
      muscle. We discuss the problem of how to reconcile the similarity of the
      myofibrillar ATPase rates at physiological temperatures with their different
      mechanical properties.

PMID- 14581214
TI  - Molecular basis of passive stress relaxation in human soleus fibers: assessment
      of the role of immunoglobulin-like domain unfolding.
AB  - Titin (also known as connectin) is the main determinant of physiological levels
      of passive muscle force. This force is generated by the extensible I-band region
      of the molecule, which is constructed of the PEVK domain and tandem
      immunoglobulin segments comprising serially linked immunoglobulin (Ig)-like
      domains. It is unresolved whether under physiological conditions Ig domains
      remain folded and act as "spacers" that set the sarcomere length at which the
      PEVK extends or whether they contribute to titin's extensibility by unfolding.
      Here we focused on whether Ig unfolding plays a prominent role in stress
      relaxation (decay of force at constant length after stretch) using mechanical and
      immunolabeling studies on relaxed human soleus muscle fibers and Monte Carlo
      simulations. Simulation experiments using Ig-domain unfolding parameters obtained
      in earlier single-molecule atomic force microscopy experiments recover the
      phenomenology of stress relaxation and predict large-scale unfolding in titin
      during an extended period (> approximately 20 min) of relaxation. By contrast,
      immunolabeling experiments failed to demonstrate large-scale unfolding. Thus,
      under physiological conditions in relaxed human soleus fibers, Ig domains are
      more stable than predicted by atomic force microscopy experiments. Ig-domain
      unfolding did not become more pronounced after gelsolin treatment, suggesting
      that the thin filament is unlikely to significantly contribute to the mechanical
      stability of the domains. We conclude that in human soleus fibers, Ig unfolding
      cannot solely explain stress relaxation.

PMID- 14581215
TI  - Hyper-mobile water is induced around actin filaments.
AB  - When introduced into water, some molecules and ions (solutes) enforce the
      hydrogen-bonded network of neighboring water molecules that are thus restrained
      from thermal motions and are less mobile than those in the bulk phase (structure
      making or positive hydration effect), and other solutes cause the opposite effect
      (structure-breaking or negative hydration effect). Using a method of microwave
      dielectric spectroscopy recently developed to measure the rotational mobility
      (dielectric relaxation frequency) of water hydrating proteins and the volume of
      hydration shells, the hydration of actin filament (F-actin) has been studied. The
      results indicate that F-actin exhibits both the structure-making and structure
      breaking effects. Thus, apart from the water molecules with lowered rotational
      mobility that make up a typical hydration shell, there are other water molecules
      around the F-actin which have a much higher mobility than that of bulk water. No
      such dual hydration has been observed for myoglobin studied as the representative
      example of globular proteins which all showed qualitatively similar dielectric
      spectra. The volume fraction of the mobilized (hyper-mobile) water is roughly
      equal to that of the restrained water, which is two-thirds of the molecular
      volume of G-actin in size. The dielectric spectra of aqueous solutions of urea
      and potassium-halide salts have also been studied. The results suggest that urea
      and I(-) induce the hyper-mobile states of water, which is consistent with their
      well-known structure-breaking effect. The molecular surface of actin is rich in
      negative charges, which along with its filamentous structure provides a
      structural basis for the induction of a hyper-mobile state of water. A possible
      implication of the findings of the present study is discussed in relation to the
      chemomechanical energy transduction through interaction with myosin in the
      presence of ATP.

PMID- 14581216
TI  - Photo-oxidation of P740, the primary electron donor in photosystem I from
      Acaryochloris marina.
AB  - Fourier transform infrared spectroscopy (FTIR) difference spectroscopy in
      combination with deuterium exchange experiments has been used to study the photo
      oxidation of P740, the primary electron donor in photosystem I from Acaryochloris
      marina. Comparison of (P740(+)-P740) and (P700(+)-P700) FTIR difference spectra
      show that P700 and P740 share many structural similarities. However, there are
      several distinct differences also: 1), The (P740(+)-P740) FTIR difference
      spectrum is significantly altered upon proton exchange, considerably more so than
      the (P700(+)-P700) FTIR difference spectrum. The P740 binding pocket is therefore
      more accessible than the P700 binding pocket. 2), Broad, "dimer" absorption bands
      are observed for both P700(+) and P740(+). These bands differ significantly in
      substructure, however, suggesting differences in the electronic organization of
      P700(+) and P740(+). 3), Bands are observed at 2727(-) and 2715(-) cm(-1) in the
      (P740(+)-P740) FTIR difference spectrum, but are absent in the (P700(+)-P700)
      FTIR difference spectrum. These bands are due to formyl CH modes of chlorophyll
      d. Therefore, P740 consists of two chlorophyll d molecules. Deuterium-induced
      modification of the (P740(+)-P740) FTIR difference spectrum indicates that only
      the highest frequency 13(3) ester carbonyl mode of P740 downshifts, indicating
      that this ester mode is weakly H-bonded. In contrast, the highest frequency ester
      carbonyl mode of P700 is free from H-bonding. Deuterium-induced changes in
      (P740(+)-P740) FTIR difference spectrum could also indicate that one of the
      chlorophyll d 3(1) carbonyls of P740 is hydrogen bonded.

PMID- 14581217
TI  - Exciton theory for supramolecular chlorosomal aggregates: 1. Aggregate size
      dependence of the linear spectra.
AB  - The interior of chlorosomes of green bacteria forms an unusual antenna system
      organized without proteins. The steady-spectra (absorption, circular dichroism,
      and linear dichroism) have been modeled using the Frenkel Hamiltonian for the
      large tubular aggregates of bacteriochlorophylls with geometries corresponding to
      those proposed for Chloroflexus aurantiacus and Chlorobium tepidum chlorosomes.
      For the Cf. aurantiacus aggregates we apply a structure used previously (V. I.
      Prokhorenko., D. B. Steensgaard, and A. R. Holzwarth, Biophys: J. 2000, 79:2105
      2120), whereas for the Cb. tepidum aggregates a new extended model of double-tube
      aggregates, based on recently published solid-state nuclear magnetic resonance
      studies (B.-J. van Rossum, B. Y. van Duhl, D. B. Steensgaard, T. S. Balaban, A.
      R. Holzwarth, K. Schaffner, and H. J. M. de Groot, Biochemistry 2001, 40:1587
      1595), is developed. We find that the circular dichroism spectra depend strongly
      on the aggregate length for both types of chlorosomes. Their shape changes from
      "type-II" (negative at short wavelengths to positive at long wavelengths) to the
      "mixed-type" (negative-positive-negative) in the nomenclature proposed in K.
      Griebenow, A. R. Holzwarth, F. van Mourik, and R. van Grondelle, Biochim:
      Biophys. Acta 1991, 1058:194-202, for an aggregate length of 30-40
      bacteriochlorophyll molecules per stack. This "size effect" on the circular
      dichroism spectra is caused by appearance of macroscopic chirality due to
      circular distribution of the transition dipole moment of the monomers. We
      visualize these distributions, and also the corresponding Frenkel excitons, using
      a novel presentation technique. The observed size effects provide a key to
      explain many previously puzzling and seemingly contradictory experimental data in
      the literature on the circular and linear dichroism spectra of seemingly
      identical types of chlorosomes.

PMID- 14581218
TI  - Role of backbone hydration and salt-bridge formation in stability of alpha-helix
      in solution.
AB  - We test molecular level hypotheses for the high thermal stability of alpha
      helical conformations of alanine-based peptides by performing detailed atomistic
      simulations of a 20-amino-acid peptide with explicit treatment of water. To
      assess the contribution of large side chains to alpha-helix stability through
      backbone desolvation and salt-bridge formation, we simulate the alanine-rich
      peptide, Ac-YAEAAKAAEAAKAAEAAKAF-Nme, referred to as the EK peptide, that has
      three pairs of "i, i + 3" glutamic acid(-) and lysine(+) substitutions. Efficient
      configurational sampling of the EK peptide over a wide temperature range enabled
      by the replica exchange molecular dynamics technique allows characterization of
      the stability of alpha-helix with respect to heat-induced unfolding. We find that
      near ambient temperatures, the EK peptide predominately samples alpha-helical
      configurations with 80% fractional helicity at 300 K. The helix melts over a
      broad range of temperatures with melting temperature, T(m), equal to 350 K, that
      is significantly higher than the T(m) of a 21-residue polyalanine peptide, A(21).
      Salt-bridges between oppositely charged Glu(-) and Lys(+) side chains can, in
      principle, provide thermal stability to alpha-helical conformers. For the
      specific EK peptide sequence, we observe infrequent formation of Glu-Lys salt
      bridges (with approximately 10-20% probability) and therefore we conclude that
      salt-bridge formation does not contribute significantly to the EK peptide's
      helical stability. However, lysine side chains are found to shield specific "i, i
      + 4" backbone hydrogen bonds from water, indicating that large side-chain
      substituents can play an important role in stabilizing alpha-helical
      configurations of short peptides in aqueous solution through mediation of water
      access to backbone hydrogen bonds. These observations have implications on
      molecular engineering of peptides and biomolecules in the design of their
      thermostable variants where the shielding mechanism can act in concert with other
      factors such as salt-bridge formation, thereby increasing thermal stability
      considerably.

PMID- 14581219
TI  - Design and structure-based study of new potential FKBP12 inhibitors.
AB  - Based on the structure of FKBP12 complexed with FK506 or rapamycin, with computer
      aided design, two neurotrophic ligands, (3R)-4-(p-Toluenesulfonyl)-1,4-thiazane-3
      carboxylic acid-L-Leucine ethyl ester and (3R)-4-(p-Toluenesulfonyl)-1,4-thiazane
      3-carboxylic acid-L-phenylalanine benzyl ester, were designed and synthesized.
      Fluorescence experiments were used to detect the binding affinity between FKBP12
      and these two ligands. Complex structures of FKBP12 with these two ligands were
      obtained by x-ray crystallography. In comparing FKBP12-rapamycin complex and
      FKBP12-FK506 complex as well as FKBP12-GPI-1046 solution structure with these new
      complexes, significant volume and surface area effects and obvious contact
      changes were detected which are expected to cause their different binding
      energies-showing these two novel ligands will become more effective neuron
      regeneration drugs than GPI-1046, which is currently undergoing phase II clinical
      trail as a neurotrophic drug. Analysis of volume and surface area effects also
      gives a new clue for structure-based drug design.

PMID- 14581220
TI  - Sound velocity and elasticity of tetragonal lysozyme crystals by Brillouin
      spectroscopy.
AB  - Quasilongitudinal sound velocities and the second-order elastic moduli of
      tetragonal hen egg-white lysozyme crystals were determined as a function of
      relative humidity (RH) by Brillouin scattering. In hydrated crystals the measured
      sound velocities in the [110] plane vary between 2.12 +/- 0.03 km/s along the
      [001] direction and 2.31 +/- 0.08 km/s along the [110] direction. Dehydration
      from 98% to 67% RH increases the sound velocities and decreases the velocity
      anisotropy in (110) from 8.2% to 2.0%. A discontinuity in velocity and an
      inversion of the anisotropy is observed with increasing dehydration providing
      support for the existence of a structural transition below 88% RH. Brillouin
      linewidths can be described by a mechanical model in which the phonon is coupled
      to a relaxation mode of hydration water with a single relaxation time of 55 +/- 5
      ps. At equilibrium hydration (98% RH) the longitudinal moduli C(11) + C(12) +
      2C(66) = 12.81 +/- 0.08 GPa, C(11) = 5.49 +/- 0.03 GPa, and C(33) = 5.48 +/- 0.05
      GPa were directly determined. Inversion of the measured sound velocities in the
      [110] plane constrains the combination C(44) + (1/2)C(13) to 2.99 +/- 0.05 GPa.
      Further constraints on the elastic tensor are obtained by combining the Brillouin
      quasilongitudinal results with axial compressibilities determined from high
      pressure x-ray diffraction. We constrain the adiabatic bulk modulus to the range
      2.7-5.3 GPa.

PMID- 14581221
TI  - Perturbation of protein tertiary structure in frozen solutions revealed by 1
      anilino-8-naphthalene sulfonate fluorescence.
AB  - Although freeze-induced perturbations of the protein native fold are common, the
      underlying mechanism is poorly understood owing to the difficulty of monitoring
      their structure in ice. In this report we propose that binding of the
      fluorescence probe 1-anilino-8-naphthalene sulfonate (ANS) to proteins in ice can
      provide a useful monitor of ice-induced strains on the native fold. Experiments
      conducted with copper-free azurin from Pseudomonas aeruginosa, as a model protein
      system, demonstrate that in frozen solutions the fluorescence of ANS is enhanced
      several fold and becomes blue shifted relative free ANS. From the enhancement
      factor it is estimated that, at -13 degrees C, on average at least 1.6 ANS
      molecules become immobilized within hydrophobic sites of apo-azurin, sites that
      are destroyed when the structure is largely unfolded by guanidinium
      hydrochloride. The extent of ANS binding is influenced by temperature of ice as
      well as by conditions that affect the stability of the globular structure.
      Lowering the temperature from -4 degrees C to -18 degrees C leads to an apparent
      increase in the number of binding sites, an indication that low temperature and
      /or a reduced amount of liquid water augment the strain on the protein tertiary
      structure. It is significant that ANS binding is practically abolished when the
      native fold is stabilized upon formation of the Cd(2+) complex or on addition of
      glycerol to the solution but is further enhanced in the presence of NaSCN, a
      known destabilizing agent. The results of the present study suggest that the ANS
      binding method may find practical utility in testing the effectiveness of various
      additives employed in protein formulations as well as to devise safer freeze
      drying protocols of pharmaceutical proteins.

PMID- 14581223
TI  - Nonnative interactions between cysteines direct productive assembly of P22
      tailspike protein.
AB  - Nonnative disulfide bond formation can play a critical role in the assembly of
      disulfide bonded proteins. During the folding and assembly of the P22 tailspike
      protein, nonnative disulfide bonds form both in vivo and in vitro. However, the
      mechanism and identity of cysteine disulfide pairs remains elusive, particularly
      for P22 tailspike, which contains no disulfide bonds in its native, functional
      form. Understanding the interactions between cysteine residues is important for
      developing a mechanistic model for the role of nonnative cysteines in P22
      tailspike assembly. Prior in vivo studies have suggested that cysteines 496, 613,
      and 635 are the most likely site for sulfhydryl reactivity. Here we demonstrate
      that these three cysteines are critical for efficient assembly of tailspike
      trimers, and that interactions between cysteine pairs lead to productive assembly
      of native tailspike.

PMID- 14581224
TI  - Amino acid substitutions in a long flexible sequence influence thermodynamics and
      internal dynamic properties of winged helix protein genesis and its DNA complex.
AB  - The hepatocyte nuclear factor (HNF)-3 homologous DNA binding domain is a highly
      conserved motif that contains a well-folded helix-turn-helix motif and two highly
      dynamic wings. Although the function and the properties of this motif have been
      intensively studied, the role of the internal wing (wing 1) is not well
      understood. In this study, amino acid substitutions were introduced into wing 1
      of a conserved HNF-3 homologous protein, Genesis, and heteronuclear NMR, circular
      dichroism, DNA gel-shift assay, and fluorescent methods were employed to study
      and compare the properties of both wild-type and variant Genesis proteins. The
      data indicate that even though the substitutions are located on a dynamic wing
      outside the hydrophobic core sequences, they still globally influence biophysical
      properties of DNA-free Genesis and its DNA complex.

PMID- 14581222
TI  - Modeling the binding sites of anti-hen egg white lysozyme antibodies HyHEL-8 and
      HyHEL-26: an insight into the molecular basis of antibody cross-reactivity and
      specificity.
AB  - Three antibodies, HyHEL-8 (HH8), HyHEL-10 (HH10), and HyHEL-26 (HH26) are
      specific for the same epitope on hen egg white lysozyme (HEL), and share >90%
      sequence homology. Their affinities vary by several orders of magnitude, and
      among the three antibodies, HH8 is the most cross-reactive with kinetics of
      binding that are relatively invariable compared to HH26, which is highly specific
      and has quite variable kinetics. To investigate structural correlates of these
      functional variations, the Fv regions of HH8 and HH26 were homology-modeled using
      the x-ray structure of the well-characterized HH10-HEL complex as template. The
      binding site of HH26 is most charged, least hydrophobic, and has the greatest
      number of intramolecular salt bridges, whereas that of HH8 is the least charged,
      most hydrophobic and has the fewest intramolecular salt bridges. The modeled HH26
      HEL structure predicts the recently determined x-ray structure of HH26, (Li et
      al., 2003, Nat. Struct. Biol. 10:482-488) with a root-mean-square deviation of
      1.03 A. It is likely that the binding site of HH26 is rendered rigid by a network
      of intramolecular salt bridges whereas that of HH8 is flexible due to their
      absence. HH26 also has the most intermolecular contacts with the antigen whereas
      HH8 has the least. HH10 has these properties intermediate to HH8 and HH26. The
      structurally rigid binding site with numerous specific contacts bestows
      specificity on HH26 whereas the flexible binding site with correspondingly fewer
      contacts enables HH8 to be cross-reactive. Results suggest that affinity
      maturation may select for high affinity antibodies with either "lock-and-key"
      preconfigured binding sites, or "preconfigured flexibility" by modulating
      combining site flexibility.

PMID- 14581225
TI  - Predissociated dimers and molten globule monomers in the equilibrium unfolding of
      yeast glutathione reductase.
AB  - The equilibrium unfolding of dimeric yeast glutathione reductase (GR) by
      guanidine hydrochloride (GdnHCl) was investigated. Unfolding was monitored by a
      variety of techniques, including intrinsic fluorescence emission, anisotropy and
      iodide quenching measurements, far-ultraviolet circular dichroism and thiol
      reactivity measurements. At 1 M GdnHCl, one thiol group of GR became accessible
      to modification with 5,5'-dithiobis-(2-nitrobenzoic) acid (DTNB), whereas no
      changes could be detected in the spectroscopic properties (fluorescence, circular
      dichroism) of the protein. Between 2 and 3 M GdnHCl, two partially folded
      intermediate states possessing flexible tertiary structures (revealed by
      fluorescence data) but compact secondary structures (as indicated by circular
      dichroism measurements) were identified. The quaternary structure of GR in the
      presence of GdnHCl was also investigated by size-exclusion liquid chromatography.
      These results indicated the presence of an expanded predissociated dimer at 2.5 M
      GdnHCl and partially folded monomers at 3 M GdnHCl. Taken together, these results
      suggest the existence of two molten-globule-like intermediate species (one
      dimeric and one monomeric) in the unfolding of GR. The results are discussed in
      terms of the mechanism of GR folding and dimerization.

PMID- 14581226
TI  - TNP-AMP binding to the sarcoplasmic reticulum Ca(2+)-ATPase studied by infrared
      spectroscopy.
AB  - Infrared spectroscopy was used to monitor the conformational change of 2',3'-O
      (2,4,6-trinitrophenyl)adenosine 5'-monophosphate (TNP-AMP) binding to the
      sarcoplasmic reticulum Ca(2+)-ATPase. TNP-AMP binding was observed in a
      competition experiment: TNP-AMP is initially bound to the ATPase but is then
      replaced by beta,gamma-iminoadenosine 5'-triphosphate (AMPPNP) after AMPPNP
      release from P(3)-1-(2-nitrophenyl)ethyl AMPPNP (caged AMPPNP). The resulting
      infrared difference spectra are compared to those of AMPPNP binding to the free
      ATPase, to obtain a difference spectrum that reflects solely TNP-AMP binding to
      the Ca(2+)-ATPase. TNP-AMP used as an ATP analog in the crystal structure of the
      sarcoplasmic reticulum Ca(2+)-ATPase was found to induce a conformational change
      upon binding to the ATPase. It binds with a binding mode that is different from
      that of AMPPNP, ATP, and other tri- and diphosphate nucleotides: TNP-AMP binding
      causes partially opposite and smaller conformational changes compared to ATP or
      AMPPNP. The conformation of the TNP-AMP ATPase complex is more similar to that of
      the E1Ca(2) state than to that of the E1ATPCa(2) state. Regarding the use of
      infrared spectroscopy as a technique for ligand binding studies, our results show
      that infrared spectroscopy is able to distinguish different binding modes.

PMID- 14581227
TI  - Unfolding of globular proteins: monte carlo dynamics of a realistic reduced
      model.
AB  - Reduced lattice models of proteins and Monte Carlo dynamics were used to simulate
      the initial stages of the unfolding of several proteins of various structural
      types, and the results were compared to experiment. The models semiquantitatively
      reproduce the approximate order of events of unfolding as well as subtle mutation
      effects and effects resulting from differences in sequences of similar folds. The
      short-time mobility of particular residues, observed in simulations, correlates
      with the crystallographic temperature factor. The main factor controlling
      unfolding is the native state topology, with sequence playing a less important
      role. The correlation with various experiments, especially for sequence-specific
      effects, strongly suggests that properly designed reduced models of proteins can
      be used for qualitative studies (or prediction) of protein unfolding pathways.

PMID- 14581228
TI  - An isothermal titration calorimetry study on the binding of four volatile general
      anesthetics to the hydrophobic core of a four-alpha-helix bundle protein.
AB  - A molecular understanding of volatile anesthetic mechanisms of action will
      require structural descriptions of anesthetic-protein complexes. Previous work
      has demonstrated that the halogenated alkane volatile anesthetics halothane and
      chloroform bind to the hydrophobic core of the four-alpha-helix bundle (Aalpha(2)
      L38M)(2) (Johansson et al., 2000, 2003). This study shows that the halogenated
      ether anesthetics isoflurane, sevoflurane, and enflurane are also bound to the
      hydrophobic core of the four-alpha-helix bundle, using isothermal titration
      calorimetry. Isoflurane and sevoflurane both bound to the four-alpha-helix bundle
      with K(d) values of 140 +/- 10 micro M, whereas enflurane bound with a K(d) value
      of 240 +/- 10 micro M. The DeltaH degrees values associated with isoflurane,
      sevoflurane, and enflurane binding were -7.7 +/- 0.1 kcal/mol, -8.2 +/- 0.2
      kcal/mol, and -7.2 +/- 0.1 kcal/mol, respectively. The DeltaS degrees values
      accompanying isoflurane, sevoflurane, and enflurane binding were -8.5 cal/mol K, 
      10.4 cal/mol K, and -8.0 cal/mol K, respectively. The results indicate that the
      hydrophobic core of (Aalpha(2)-L38M)(2) is able to accommodate three modern ether
      anesthetics with K(d) values that approximate their clinical EC(50) values. The
      DeltaH degrees values point to the importance of polar interactions for volatile
      general anesthetic binding, and suggest that hydrogen bonding to the ether
      oxygens may be operative.

PMID- 14581229
TI  - Pathway shifts and thermal softening in temperature-coupled forced unfolding of
      spectrin domains.
AB  - Pathways of unfolding a protein depend in principle on the perturbation-whether
      it is temperature, denaturant, or even forced extension. Widely-shared, helical
      bundle spectrin repeats are known to melt at temperatures as low as 40-45 degrees
      C and are also known to unfold via multiple pathways as single molecules in
      atomic force microscopy. Given the varied roles of spectrin family proteins in
      cell deformability, we sought to determine the coupled effects of temperature on
      forced unfolding. Bimodal distributions of unfolding intervals are seen at all
      temperatures for the four-repeat beta(1-4) spectrin-an alpha-actinin homolog. The
      major unfolding length corresponds to unfolding of a single repeat, and a minor
      peak at twice the length corresponds to tandem repeats. Increasing temperature
      shows fewer tandem events but has no effect on unfolding intervals. As T
      approaches T(m), however, mean unfolding forces in atomic force microscopy also
      decrease; and circular dichroism studies demonstrate a nearly proportional
      decrease of helical content in solution. The results imply a thermal softening of
      a helical linker between repeats which otherwise propagates a helix-to-coil
      transition to adjacent repeats. In sum, structural changes with temperature
      correlate with both single-molecule unfolding forces and shifts in unfolding
      pathways.

PMID- 14581230
TI  - Ligand-receptor kinetics measured by total internal reflection with fluorescence
      correlation spectroscopy.
AB  - Total internal reflection excitation used in combination with fluorescence
      correlation spectroscopy (TIR-FCS) is a method for characterizing the dynamic
      behavior and absolute concentrations of fluorescent molecules near or at the
      interface of a planar substrate and a solution. In this work, we demonstrate for
      the first time the use of TIR-FCS for examining the interaction kinetics of
      fluorescent ligands in solution which specifically and reversibly associate with
      receptors in substrate-supported planar membranes. Fluorescence fluctuation
      autocorrelation functions were obtained for a fluorescently labeled IgG
      reversibly associating with the mouse receptor FcgammaRII, which was purified and
      reconstituted into substrate-supported planar membranes. Data were obtained as a
      function of the IgG solution concentration, the Fc receptor surface density, the
      observation area size, and the incident intensity. Best fits of the
      autocorrelation functions to appropriate theoretical forms gave measures of the
      average surface density of bound IgG, the local solution concentration of IgG,
      the kinetic rate constant for surface dissociation, and the rate of diffusion
      through the depth of the evanescent field. The average number of observed
      fluorescent molecules, both in solution and bound to the surface, scaled with the
      solution concentration of IgG, observation area size, and Fc receptor surface
      density as expected. The dissociation rate constant and rate of diffusion through
      the evanescent field agree with previous results, and all measured parameters
      were independent of the incident intensity.

PMID- 14581231
TI  - Formation of transient oxygen complexes of cytochrome p450 BM3 and nitric oxide
      synthase under high pressure.
AB  - The kinetics of formation and transformation of oxygen complexes of two heme
      thiolate proteins (the F393H mutant of cytochrome P450 BM3 and the oxygenase
      domain of endothelial nitric oxide synthase, eNOS) were studied under high
      pressure. For BM3, oxygen-binding characteristics (rate and activation volume)
      matched those measured for CO-binding. In contrast, pressure revealed a different
      CO- and oxygen-binding mechanism for eNOS, suggesting that it is hazardous to
      take CO-binding as a model for oxygen-binding. With eNOS, a ferric NO complex is
      formed as an intermediate in the second reaction cycle. Here we report the
      pressure stability of this compound. Furthermore, in the presence of 4-amino
      tetrahydrobiopterin (ABH(4)), an analog to the natural second electron donor
      tetrahydrobiopterin (BH(4)), biphasic pressure profiles of the oxygen-binding
      rates were observed, both in the first and the second reaction cycles, indicative
      of the formation of an additional reaction intermediate. This was confirmed by
      experiments where ABH(4) was replaced by ABH(2), a cofactor which cannot deliver
      an electron. Altogether, high pressure appears to be a useful tool to
      characterize elementary steps in the reaction cycle of heme-thiolate proteins.

PMID- 14581232
TI  - Glucose and mannitol diffusion in human dura mater.
AB  - An in vitro experimental study of the control of the human dura mater optical
      properties at administration of aqueous solutions of glucose and mannitol has
      been presented. The significant increase of the dura mater optical transmittance
      under action of immersion liquids has been demonstrated. Diffusion coefficients
      of glucose and mannitol in the human dura mater tissue at 20 degrees C have been
      estimated as (1.63 +/- 0.29) x 10(-6)cm(2)/s and as (1.31 +/- 0.41) x 10(-6)
      cm(2)/s, respectively. Experiments show that administration of immersion liquids
      allows for the effective control of tissue optical characteristics that make dura
      mater more transparent, thereby increasing the ability of light penetration
      through the tissue.

PMID- 14581233
TI  - Modeling the role of myosin 1c in neuronal growth cone turning.
AB  - We addressed the mechanical basis for how embryonic chick dorsal root ganglion
      growth cones turn on a uniform substrate of laminin-1. Turning is significantly
      correlated with lamellipodial area but not with filopodial length. We assessed
      the lamellipodial contribution to turning by asymmetric micro-CALI of myosin
      isoforms that causes localized lamellipodial expansion (myosin 1c) or filopodial
      retraction (myosin V). Episodes of asymmetric micro-CALI of myosin 1c (or myosin
      1c and V together) caused significant turning of the growth cone. In contrast,
      repeated micro-CALI of myosin V or irradiation without added antibody did not
      turn growth cones. These findings argue that lamellipodia and not filopodia are
      necessary for growth cone turning. To model the role of myosin 1c on growth cone
      turning, we fitted the measured trajectories from asymmetric micro-CALI of myosin
      1c-treated and untreated growth cones to the persistent random walk model. The
      first parameter in this equation, root-mean-square speed, is indistinguishable
      between the two data sets whereas the second parameter, the persistence of
      motion, is significantly increased (2.5-fold) as a result of asymmetric
      inactivation of myosin 1c by micro-CALI. This analysis demonstrates that growth
      cone turning results from an increase in the persistence of directional motion
      rather than a change in speed. Taken together, our results suggest that myosin 1c
      is a molecular correlate for directional persistence underlying growth cone
      motility.

PMID- 14581234
TI  - Influence of type I collagen surface density on fibroblast spreading, motility,
      and contractility.
AB  - We examine the relationships of three variables (projected area, migration speed,
      and traction force) at various type I collagen surface densities in a population
      of fibroblasts. We observe that cell area is initially an increasing function of
      ligand density, but that above a certain transition level, increases in surface
      collagen cause cell area to decline. The threshold collagen density that
      separates these two qualitatively different regimes, approximately 160 molecules/
      microm(2), is approximately equal to the cell surface density of integrin
      molecules. These results suggest a model in which collagen density induces a
      qualitative transition in the fundamental way that fibroblasts interact with the
      substrate. At low density, the availability of collagen binding sites is limiting
      and the cells simply try to flatten as much as possible by pulling on the few
      available sites as hard as they can. The force per bond under these conditions
      approaches 100 pN, approximately equal to the force required for rupture of
      integrin-peptide bonds. In contrast, at high collagen density adhesion, traction
      force and motility are limited by the availability of free integrins on the cell
      surface since so many of these receptors are bound to the surface ligand and the
      force per bond is very low.

PMID- 14581235
TI  - A three-dimensional viscoelastic model for cell deformation with experimental
      verification.
AB  - A three-dimensional viscoelastic finite element model is developed for cell
      micromanipulation by magnetocytometry. The model provides a robust tool for
      analysis of detailed strain/stress fields induced in the cell monolayer produced
      by forcing one microbead attached atop a single cell or cell monolayer on a basal
      substrate. Both the membrane/cortex and the cytoskeleton are modeled as Maxwell
      viscoelastic materials, but the structural effect of the membrane/cortex was
      found to be negligible on the timescales corresponding to magnetocytometry.
      Numerical predictions are validated against experiments performed on NIH 3T3
      fibroblasts and previous experimental work. The system proved to be linear with
      respect to cytoskeleton mechanical properties and bead forcing. Stress and strain
      patterns were highly localized, suggesting that the effects of magnetocytometry
      are confined to a region extending <10 microm from the bead. Modulation of cell
      height has little effect on the results, provided the monolayer is >5 micro m
      thick. NIH 3T3 fibroblasts exhibited a viscoelastic timescale of approximately 1
      s and a shear modulus of approximately 1000 Pa.

PMID- 14581236
TI  - Quantitative analysis of spontaneous mitochondrial depolarizations.
AB  - Spontaneous transient depolarizations in mitochondrial membrane potential
      (DeltaPsi(m)), mitochondrial flickers, have been observed in isolated
      mitochondria and intact cells using the fluorescent probe, tetramethylrhodamine
      ethyl ester (TMRE). In theory, the ratio of [TMRE] in cytosol and mitochondrion
      allows DeltaPsi(m) to be calculated with the Nernst equation, but this has proven
      difficult in practice due to fluorescence quenching and binding of dye to
      mitochondrial membranes. We developed a new method to determine the amplitude of
      flickers in terms of millivolts of depolarization. TMRE fluorescence was
      monitored using high-speed, high-sensitivity three-dimensional imaging to track
      individual mitochondria in freshly dissociated smooth muscle cells. Resting
      mitochondrial fluorescence, an exponential function of resting DeltaPsi(m),
      varied among mitochondria and was approximately normally distributed. Spontaneous
      changes in mitochondrial fluorescence, indicating depolarizations and
      repolarizations in DeltaPsi(m), were observed. The depolarizations were
      reversible and did not result in permanent depolarization of the mitochondria.
      The magnitude of the flickers ranged from <10 mV to >100 mV with a mean of 17.6
      +/- 1.0 mV (n = 360) and a distribution skewed to smaller values. Nearly all
      mitochondria flickered, and they did so independently of one another, indicating
      that mitochondria function as independent units in the myocytes employed here.

PMID- 14581237
TI  - Spontaneous changes in mitochondrial membrane potential in single isolated brain
      mitochondria.
AB  - In this study we measured DeltaPsim in single isolated brain mitochondria using
      rhodamine 123. Mitochondria were attached to coverslips and superfused with K(+)
      based HEPES-buffer medium supplemented with malate and glutamate. In
      approximately 70% of energized mitochondria we observed large amplitude
      spontaneous fluctuations in DeltaPsim with a time course comparable to that
      observed previously in mitochondria of intact cells. The other 30% of
      mitochondria maintained a stable DeltaPsim. Some of the "stable" mitochondria
      began to fluctuate spontaneously during the recording period. However, none of
      the initially fluctuating mitochondria became stable. Upon the removal of
      substrates from the medium or application of small amounts of Ca(2+), rhodamine
      123 fluorescence rapidly dropped to background values in fluctuating
      mitochondria, while nonfluctuating mitochondria depolarized with a delay and
      often began to fluctuate before complete depolarization. The changes in DeltaPsim
      were not connected to oxidant production since reducing illumination or the
      addition of antioxidants had no effect on DeltaPsim. Fluctuating mitochondria did
      not lose calcein, nor was there any effect of cyclosporin A on DeltaPsim, which
      ruled out a contribution of permeability transition. We conclude that the
      fluctuations in DeltaPsim reflect an intermediate, unstable state of mitochondria
      that may lead to or reflect mitochondrial dysfunction.

PMID- 14581238
TI  - Role of the aromatic ring of Tyr43 in tetraheme cytochrome c(3) from
      Desulfovibrio vulgaris Miyazaki F.
AB  - Tyrosine 43 is positioned parallel to the fifth heme axial ligand, His34, of heme
      1 in the tetraheme cytochrome c(3). The replacement of tyrosine with leucine
      increased the redox potential of heme 1 by 44 and 35 mV at the first and last
      reduction steps, respectively; its effects on the other hemes are small. In
      contrast, the Y43F mutation hardly changed the potentials. It shows that the
      aromatic ring at this position contributes to lowering the redox potential of
      heme 1 locally, although this cannot be the major contribution to the extremely
      low redox potentials of cytochrome c(3). Furthermore, temperature-dependent line
      width broadening in partially reduced samples established that the aromatic ring
      at position 43 participates in the control of the kinetics of intramolecular
      electron transfer. The rate of reduction of Y43L cytochrome c(3) by 5
      deazariboflavin semiquinone under partially reduced conditions was significantly
      different from that of the wild type in the last stage of the reduction,
      supporting the involvement of Tyr43 in regulation of reduction kinetics. The
      mutation of Y43L, however, did not induce a significant change in the crystal
      structure.

PMID- 14581239
TI  - Distinct quantal features of AMPA and NMDA synaptic currents in hippocampal
      neurons: implication of glutamate spillover and receptor saturation.
AB  - Excitatory postsynaptic currents (EPSCs) were studied in the CA1 pyramidal cells
      of rat hippocampal slices. Components mediated by alpha-amino-3-hydroxy-5
      methylisoxazole-4-proprionic acid (AMPA) and by N-methyl-D-aspartate (NMDA)
      receptors were separated pharmacologically. Quantal parameters of AMPA and NMDA
      receptor-mediated EPSCs were obtained using both maximal likelihood and
      autocorrelation techniques. Enhancement of transmitter release with 4
      aminopyridine caused a significant increase in quantal size of NMDA EPSC. This
      was accompanied by a slowing of the EPSC decay. The maximal number of quanta in
      the NMDA current was unchanged, while the probability of quantal event
      dramatically enhanced. In contrast, neither the quantal size nor the kinetics of
      AMPA EPSC was altered by 4-aminopyridine, while the maximal number of quanta
      increased. These changes in the quantal parameters are consistent with a
      transition to multivesicular release of the neurotransmitter. Spillover of
      excessive glutamate on the nonsynaptic areas of dendritic spines causes an
      increase in the quantal size of NMDA synaptic current. The difference in quantal
      behavior of AMPA and NMDA EPSCs implies that different mechanisms underlie their
      quantization: the additive response of nonsaturated AMPA receptors contrasts with
      the variable involvement of saturated intrasynaptic and nonsaturated
      extrasynaptic NMDA receptors.

PMID- 14581240
TI  - Na/Ca exchange and Na/K-ATPase function are equally concentrated in transverse
      tubules of rat ventricular myocytes.
AB  - Formamide-induced detubulation of rat ventricular myocytes was used to
      investigate the functional distribution of the Na/Ca exchanger (NCX) and Na/K
      ATPase between the t-tubules and external sarcolemma. Detubulation resulted in a
      32% decrease in cell capacitance, whereas cell volume was unchanged. Thus, the
      surface-to-volume ratio was used to assess the success of detubulation. NCX
      current (I(NCX)) and Na/K pump current (I(pump)) were recorded using whole-cell
      patch clamp, as Cd-sensitive and K-activated currents, respectively. Both inward
      and outward I(NCX) density was significantly reduced by approximately 40% in
      detubulated cells. I(NCX) density at 0 mV decreased from 0.19 +/- 0.03 to 0.10 +/
      0.03 pA/pF upon detubulation. I(pump) density was also lower in detubulated
      myocytes over the range of voltages (-50 to +100 mV) and internal [Na] ([Na](i))
      investigated (7-22 mM). At [Na](i) = 10 mM and -20 mV, I(pump) density was
      reduced by 39% in detubulated myocytes (0.28 +/- 0.02 vs. 0.17 +/- 0.03 pA/pF),
      but the apparent K(m) for [Na](i) was unchanged (16.9 +/- 0.4 vs. 17.0 +/- 0.3
      mM). These results indicate that although thet-tubules represent only
      approximately 32% of the total sarcolemma, they contribute approximately 60% to
      the total I(NCX) and I(pump). Thus, the functional density of NCX and Na/K pump
      in the t-tubules is 3-3.5-fold higher than in the external sarcolemma.

PMID- 14581242
TI  - On the precise meaning of extension in the interpretation of polymer-chain
      stretching experiments.

PMID- 14581244
TI  - Ethical challenges of partial do-not-resuscitate (DNR) orders: placing DNR orders
      in the context of a life-threatening conditions care plan.
AB  - Do-not-resuscitate (DNR) orders are commonly found in treatment plans for
      patients near the end of life. Orders for partial resuscitation (eg, "do not
      intubate") have evolved from DNR orders. Although the ethics of DNR orders have
      been widely examined in the medical literature, little has been written about the
      ethics of partial resuscitation. This article explores the ethical implications
      of partial DNR orders and identifies the need to develop care plans addressing
      life-threatening conditions for patients with DNR orders.

PMID- 14581241
TI  - Spatial distribution of Ca(2+) signals during repetitive depolarizing stimuli in
      adrenal chromaffin cells.
AB  - Exocytosis in adrenal chromaffin cells is strongly influenced by the pattern of
      stimulation. To understand the dynamic and spatial properties of the underlying
      Ca(2+) signal, we used pulsed laser Ca(2+) imaging to capture Ca(2+) gradients
      during stimulation by single and repetitive depolarizing stimuli. Short single
      pulses (10-100 ms) lead to the development of submembrane Ca(2+) gradients, as
      previously described (F. D. Marengo and J. R. Monck, 2000, Biophysical Journal,
      79:1800-1820). Repetitive stimulation with trains of multiple pulses (50 ms each,
      2Hz) produce a pattern of intracellular Ca(2+) increase that progressively
      changes from the typical Ca(2+) gradient seen after a single pulse to a Ca(2+)
      increase throughout the cell that peaks at values 3-4 times higher than the
      maximum values obtained at the end of single pulses. After seven or more pulses,
      the fluorescence increase was typically larger in the interior of the cell than
      in the submembrane region. The pattern of Ca(2+) gradient was not modified by
      inhibitors of Ca(2+)-induced Ca(2+) release (ryanodine), inhibitors of IP(3)
      induced Ca(2+) release (xestospongin), or treatments designed to deplete
      intracellular Ca(2+) stores (thapsigargin). However, we found that the large
      fluorescence increase in the cell interior spatially colocalized with the
      nucleus. These results can be simulated using mathematical models of Ca(2+)
      redistribution in which the nucleus takes up Ca(2+) by active or passive
      transport mechanisms. These results show that chromaffin cells can respond to
      depolarizing stimuli with different dynamic Ca(2+) signals in the submembrane
      space, the cytosol, and the nucleus.

PMID- 14581245
TI  - Inhaled insulin provides improved glycemic control in patients with type 2
      diabetes mellitus inadequately controlled with oral agents: a randomized
      controlled trial.
AB  - BACKGROUND: The long-term benefits of good glycemic control are well established.
      The aim of this proof-of-concept study was to determine whether glycemic control
      can be improved in patients with type 2 diabetes mellitus with suboptimal
      glycemic control, despite therapeutic dosages of oral antihyperglycemic agents
      (OHAs), by the addition of preprandial inhaled insulin (INH). METHODS: Sixty
      eight patients with inadequately controlled type 2 diabetes mellitus
      (glycosylated hemoglobin, 8.1%-11.9%), despite therapy with a sulfonylurea and/or
      metformin, were randomized to receive INH in addition to their prestudy OHA
      therapy (INH + OHA group, n = 32) or to continue taking their prestudy OHA alone
      for 12 weeks (OHA group, n = 36). Premeal INH doses were delivered in 1 to 2
      inhalations of 1-mg or 3-mg doses (equivalent to 3 IU and 9 IU, respectively, of
      subcutaneously injected regular insulin). RESULTS: At week 12, there was a
      significantly greater reduction in glycosylated hemoglobin for the INH + OHA
      cohort (mean reduction, -2.3%) compared with the OHA-only cohort (mean reduction,
      -0.1%, P<.001). Eleven patients (34%) receiving INH + OHA achieved glycosylated
      hemoglobin values of less than 7%, compared with none taking OHAs only. Fasting
      plasma glucose improved significantly more in the INH + OHA group compared with
      the OHA-only group (-60.69 mg/dL (-3.37 mmol/L] greater reduction, P<.001), and
      the postprandial increase in glucose was significantly lower in those patients
      receiving INH + OHA (P =.02). There was 1 report of severe hypoglycemia in the
      INH + OHA group (home blood glucose, 54 mg/dL [3.0 mmol/L]) and a greater
      increase in body weight. Pulmonary function was unchanged in both groups.
      CONCLUSION: The addition of preprandial INH to existing OHAs improves glycemic
      control without the need for injections in patients with type 2 diabetes mellitus
      failing to achieve satisfactory control with OHAs alone.

PMID- 14581246
TI  - Relevance of carotid stenosis progression as a predictor of ischemic neurological
      outcomes.
AB  - BACKGROUND: The progression of carotid stenosis may be a better predictor of
      adverse neurological outcomes than a single measurement of stenosis in
      asymptomatic patients. METHODS: Retrospective review of prospectively collected
      data from a noninvasive vascular surgery laboratory between 1988 and 1997 at a
      Veterans Affairs Medical Center. A total of 1701 carotid arteries from 1004
      asymptomatic patients were prospectively followed by duplex ultrasonographic
      scanning. Carotid arteries treated with endarterectomy were excluded. The main
      outcome measures were ipsilateral transient ischemic attack (TIA) and
      cerebrovascular accident (CVA). RESULTS: The baseline degree of carotid stenosis
      was less than 50% of artery diameter in 75% of patients. The annual rates of
      ipsilateral TIA and CVA were each 3.3%. When categorized with respect to carotid
      artery, the annual rates of ipsilateral TIAs and CVAs were 2.0% and 2.1%,
      respectively. Univariable Cox proportional hazards modeling showed that both
      baseline carotid stenosis and progression of stenosis were significant predictors
      of the composite outcome TIA and CVA, as well as the outcome CVA alone. In
      multivariable modeling, the progression of carotid stenosis was a highly
      significant predictor of the composite outcome TIA and CVA (risk ratio [RR],
      1.68; P<.001) and of CVA alone (RR, 1.78; P<.001). However, baseline stenosis was
      found to be a significant predictor of time to the combined outcome (RR, 1.29; P
      =.01) but not of CVA alone. Clinical risk factors did not add any additional
      predictive information. CONCLUSION: The progression of carotid stenosis assessed
      by serial duplex scanning is a better predictor of ischemic neurological events
      than a single measurement of stenosis.

PMID- 14581247
TI  - Variations in product choices of frequently purchased herbs: caveat emptor.
AB  - BACKGROUND: Patients who report use of herbs to their physicians may not be able
      to accurately describe the ingredients or recommended dosage because the products
      for the same herb may differ. The purpose of this study was to describe
      variations in label information of products for each of the 10 most commonly
      purchased herbs. METHODS: Products for each of 10 herbs were surveyed in a
      convenience sample of 20 retail stores in a large metropolitan area. Herbs were
      those with the greatest sales dollars in 1998: echinacea, St John's wort, Ginkgo
      biloba, garlic, saw palmetto, ginseng, goldenseal, aloe, Siberian ginseng, and
      valerian. RESULTS: Each herb had a large range in label ingredients and
      recommended daily dose (RDD) across available products. Strengths were not
      directly comparable because of ingredient variability. Among 880 products, 43%
      were consistent with a benchmark in ingredients and RDD, 20% in ingredients only,
      and 37% were either not consistent or label information was insufficient. Price
      per RDD was a significant predictor of consistency with the benchmark, but store
      type was not. CONCLUSIONS: Persons self-medicating with an herb may be ingesting
      ingredients substantially different from that recommended by a benchmark, both in
      quantity and content. Higher price per label RDD was the best predictor of
      consistency with a benchmark. This study demonstrates that health providers and
      consumers need to closely examine label ingredients of presumably the same or
      similar herbal products.

PMID- 14581249
TI  - Current smoking, smoking cessation, and the risk of sudden cardiac death in
      patients with coronary artery disease.
AB  - BACKGROUND: Cigarette smoking is a known risk factor for sudden cardiac death
      (SCD). However, the effect of continued cigarette smoking and smoking cessation
      on SCD risk in patients with established coronary artery disease (CAD) is subject
      to controversy. We, therefore, evaluated the effect of cigarette smoking on SCD
      risk in a large cohort of patients with established CAD. METHODS: The study
      population was composed of 3122 patients with a previous myocardial infarction or
      stable angina who participated in the Bezafibrate Infarction Prevention Trial.
      Patients were prospectively followed up for a mean of 8.2 years. The primary end
      point was the incidence of SCD according to smoking status. RESULTS: Among the
      370 patients who were current smokers, 30 (8.1%) experienced SCD; 83 (4.6%) of
      the 1821 patients who had quit smoking and 43 (4.6%) of the 931 patients who had
      never smoked experienced SCD (P =.01). In multivariate analyses, current smoking
      was associated with a significant increase in the risk of SCD (hazard ratio,
      2.47; 95% confidence interval, 1.46-4.19). Patients who had stopped smoking had
      no significant increase in the risk of SCD compared with patients who had never
      smoked (hazard ratio, 1.06; 95% confidence interval, 0.70-1.62). CONCLUSIONS:
      Current cigarette smoking is a powerful independent predictor of SCD risk in
      patients with CAD. Patients who quit smoking experienced a significant reduction
      in SCD risk. Thus, efforts to reduce mortality from SCD in patients with CAD
      should include vigorous smoking cessation strategies.

PMID- 14581248
TI  - Evaluation of walking capacity over time in 500 patients with intermittent
      claudication who underwent clinical treatment.
AB  - BACKGROUND: The use of physical training in the treatment of intermittent
      claudication is well established. However, current data do not provide enough
      information about the prognosis for each case, and there are no data on how
      walking distances evolve over time with conservative treatment. The goal of this
      study was to evaluate improvement in walking capacity among patients with
      intermittent claudication who underwent unsupervised clinical treatment,
      observing whether sustained treatment would increase or decrease maximum walking
      distance, whether after 6 months there was a change in the maximum distance, and
      whether abstinence from smoking and well-conducted walking exercise had
      independent effects on the outcome. METHODS: Five hundred patients with
      intermittent claudication were surveyed in a prospective, nonrandomized, and
      uncontrolled study. Maximum walking distance and treatment compliance over time
      were analyzed. RESULTS: Nonsmoking patients who walked achieved a mean increase
      during the first 6 months of 33.70 m/mo and a mean increase thereafter of 4.24
      m/mo. Smokers who walked achieved an increase during the first 6 months only
      (mean, 42.92 m/mo). Patients who did not practice physical training exhibited no
      effect (smokers) or negligible effect (nonsmokers) from the treatment (mean, 7.58
      m/mo). CONCLUSIONS: Patients who adhered to physical training exhibited a
      significant increase in maximum walking distance during the first 6 months of
      treatment only. Patients who did not practice physical training exhibited no
      effect (smokers) or negligible effect (ex-smokers) from the treatment.

PMID- 14581250
TI  - Peripheral arterial disease: identification and implications.
AB  - Peripheral arterial disease (PAD) is most commonly a manifestation of systemic
      atherosclerosis in which the arterial lumen of the lower extremities becomes
      progressively occluded by atherosclerotic plaque. Patients with PAD are at triple
      the risk of all-cause mortality and at more than 6 times the risk of death from
      coronary heart disease as those without the disease, yet PAD is probably the most
      underdiagnosed and least aggressively managed atherosclerotic disease. In the
      diagnosis of PAD, a detailed history and physical examination are extremely
      important, although limited by a lack of consistent sensitivity and specificity.
      Other office-based noninvasive tests, including the ankle-brachial index, can be
      easily performed to confirm the diagnosis and help stratify the risk. The ankle
      brachial index correlates well with disease severity and functional symptoms and
      can also be used to assess disease progression and to predict cardiovascular and
      cerebrovascular mortality. Once diagnosed, risk factor modification, symptomatic
      relief, and secondary prevention strategies with antiplatelet agents form the
      core of medical management of PAD.

PMID- 14581251
TI  - "Successful aging": effect of subclinical cardiovascular disease.
AB  - BACKGROUND: Cardiovascular diseases are the primary cause of death in older
      adults. Among those without clinical disease, high levels of subclinical disease
      are associated with poor survival. The effect of the extent of subclinical
      cardiovascular disease on the quality of the remaining years has not been
      defined. METHODS: In a longitudinal cohort study, 2932 men and women aged 65
      years and older were followed up for 8 years to determine the likelihood of
      maintaining intact health and functioning. Successful aging was defined as
      remaining free of cardiovascular disease, cancer, and chronic obstructive
      pulmonary disease and with intact physical and cognitive functioning. RESULTS:
      Younger age at study entry and a lower extent of subclinical cardiovascular
      disease were independently associated with the likelihood of maintaining
      successful aging. In age-stratified summaries, those with subclinical disease had
      a trajectory of decline similar to subjects 5 years older without subclinical
      vascular disease. Regression analyses showed that the decline associated with
      subclinical disease was equivalent to 6.5 (95% confidence interval, 6.4-6.6)
      years of aging for women and 5.6 (95% confidence interval, 5.4-5.8) years of
      aging for men. Individual measures of the extent of cardiovascular disease,
      diabetes mellitus, smoking, and higher C-reactive protein level were also
      independently predictive of fewer years of successful aging, but none of these
      factors substantially attenuated the effect of age itself. CONCLUSIONS: There is
      a graded relationship between the extent of vascular disease measured
      noninvasively and the likelihood of maintaining intact health and function.
      Prevention of subclinical vascular disease may increase the quality and the
      quantity of years in late life.

PMID- 14581252
TI  - Restless legs syndrome symptoms in primary care: a prevalence study.
AB  - BACKGROUND: There are relatively few studies on the prevalence of restless legs
      syndrome (RLS) in the general population, even fewer that used diagnostic
      questions covering all 4 essential diagnostic criteria defining the RLS symptom
      complex, and none that have reported on the 2 RLS phenotypes for patients seen by
      family physicians. METHODS: To determine the prevalence of the symptom complex,
      diagnostic for RLS in a primary care patient population, a prospective population
      based single-center study was performed. Every adult patient presenting for care
      in a small rural primary care practice with mostly white patients was surveyed
      for a 1-year period using a validated RLS diagnostic questionnaire. RESULTS: A
      total of 2099 patients completed the questionnaire. Analysis revealed that 24.0%
      of these patients were positive for all 4 of the essential symptoms used to make
      the diagnosis of RLS and 15.3% reported these symptoms at least weekly. In
      addition, the RLS symptom complex was reported significantly more often by women
      than men and, as a whole, patients reporting the RLS symptoms were significantly
      older than patients without symptoms. The prevalence of symptoms increased with
      age until about 60 years and then showed a steady decrease thereafter. Further,
      early-onset RLS was significantly more common in women than men. CONCLUSIONS: A
      high prevalence of RLS symptoms was observed in this primary care population.
      This finding supports the need for heightened awareness in both the medical
      community and general population regarding this disorder, which can often be
      effectively treated within the primary care practice.

PMID- 14581253
TI  - How physicians perceive hospitalist services after implementation: anticipation
      vs reality.
AB  - OBJECTIVE: To determine whether internists' attitudes toward the hospitalist
      model change after implementation of a new inpatient service. DESIGN: Cross
      sectional surveys performed in 1998 and 2000. SETTING: Tertiary care hospital in
      Boston, Mass. SUBJECTS: A total of 236 internal medicine board-certified
      physicians affiliated with Beth Israel Deaconess Medical Center. MAIN OUTCOME
      MEASURES: Responses to survey items regarding attitude toward inpatient care and
      the hospitalist model. We used multivariable models to determine factors
      associated with physician responses. RESULTS: Of physicians surveyed in 2000, 236
      (69%) responded; 145 (61%) had also responded in 1998. The mean (SD) age of
      respondents was 46.4 (10.8) years; 157 (66.5%) were male; and 146 (61.9%) were
      primary care providers. In 2000, more physicians agreed that "caring for
      inpatients is an inefficient use of my time" (P<.001), and that "use of a
      hospitalist service improves quality of care" (P =.002). In 2000, more physicians
      disagreed that "use of a hospitalist service diminishes physician career
      satisfaction" (P<.001), and that "use of the hospitalist service adversely
      affects the physician-patient relationship" (P<.001). No differences were
      detected in responses to questions regarding patient satisfaction or overall
      career satisfaction. In multivariable models, older physicians were more likely
      to favor the hospitalist model; those with busier inpatient practices were more
      negative (P<.05 for each). Physician specialty or being a primary care provider
      was not associated with attitudes toward the hospitalist model. CONCLUSIONS:
      Following experience with a hospitalist system, physician attitude, including
      concerns regarding career satisfaction and relationships with patients, toward a
      voluntary hospitalist model improved. Future research should investigate whether
      the hospitalist model affects patient satisfaction and quality of care.

PMID- 14581254
TI  - Effectiveness of bupropion sustained release for smoking cessation in a health
      care setting: a randomized trial.
AB  - BACKGROUND: The efficacy of bupropion hydrochloride sustained release (SR)
      (Zyban) for smoking cessation has been evaluated in clinical trials that included
      frequent in-person behavioral counseling, but not in actual practice settings.
      OBJECTIVE: To determine the differential effectiveness of 2 doses of bupropion SR
      in combination with behavioral interventions of minimal to moderate intensity in
      an actual practice setting. DESIGN: Open-label randomized trial, with 1 year of
      follow-up. SETTING: A large health system (Group Health Cooperative) based in
      Seattle. PARTICIPANTS: Adult smokers (N = 1524) interested in quitting smoking.
      INTERVENTIONS: Participants were randomly assigned to receive 1 of 4 combinations
      of bupropion SR (150 or 300 mg) and behavioral counseling (minimal or moderate
      intensity). MAIN OUTCOME MEASURES: The primary outcome measure was self-reported
      point-prevalence 7-day nonsmoking status at 3 and 12 months following the target
      quit date. Secondary outcomes included adverse and abstinence effects reported
      since beginning treatment with bupropion SR. RESULTS: At 3 months, a
      significantly higher rate of nonsmoking was observed among those receiving the
      larger bupropion SR dose (P=.005). At 12 months, moderate intensity counseling
      was associated significantly with a higher rate of nonsmoking (P=.001). At 3
      months, the higher dose was associated with a significantly increased frequency
      of self-reported symptoms such as difficulty sleeping (P=.02), difficulty
      concentrating (P=.02), shakiness/tremor (P=.002), and gastrointestinal problems
      (P=.005)and a decreased frequency of reported desire to smoke (P=.001).
      CONCLUSIONS: In this actual practice setting, the combination of bupropion SR and
      minimal or moderate counseling was associated with 1-year quit rates of 23.6% to
      33.2%. This suggests that existing health care systems can substantially decrease
      tobacco use rates among their enrollees if they provide these modest
      interventions.

PMID- 14581255
TI  - Predictors of hospital mortality in the global registry of acute coronary events.
AB  - BACKGROUND: Management of acute coronary syndromes (ACS) should be guided by an
      estimate of patient risk. OBJECTIVE: To develop a simple model to assess the risk
      for in-hospital mortality for the entire spectrum of ACS treated in general
      clinical practice. METHODS: A multivariable logistic regression model was
      developed using 11 389 patients (including 509 in-hospital deaths) with ACS with
      and without ST-segment elevation enrolled in the Global Registry of Acute
      Coronary Events (GRACE) from April 1, 1999, through March 31, 2001. Validation
      data sets included a subsequent cohort of 3972 patients enrolled in GRACE and 12
      142 in the Global Use of Strategies to Open Occluded Coronary Arteries IIb (GUSTO
      IIb) trial. RESULTS: The following 8 independent risk factors accounted for 89.9%
      of the prognostic information: age (odds ratio [OR], 1.7 per 10 years), Killip
      class (OR, 2.0 per class), systolic blood pressure (OR, 1.4 per 20-mm Hg
      decrease), ST-segment deviation (OR, 2.4), cardiac arrest during presentation
      (OR, 4.3), serum creatinine level (OR, 1.2 per 1-mg/dL [88.4- micro mol/L]
      increase), positive initial cardiac enzyme findings (OR, 1.6), and heart rate
      (OR, 1.3 per 30-beat/min increase). The discrimination ability of the simplified
      model was excellent with c statistics of 0.83 in the derived database, 0.84 in
      the confirmation GRACE data set, and 0.79 in the GUSTO-IIb database. CONCLUSIONS:
      Across the entire spectrum of ACS and in general clinical practice, this model
      provides excellent ability to assess the risk for death and can be used as a
      simple nomogram to estimate risk in individual patients.

PMID- 14581256
TI  - Relationship of serotonergic antidepressants and need for blood transfusion in
      orthopedic surgical patients.
AB  - BACKGROUND: Several reports of various bleeding problems associated with the use
      of serotonergic antidepressants have been published. However, no information
      concerning the effect of these drugs on perioperative blood loss and blood
      transfusion requirements during orthopedic surgery is available. The objective of
      this study was to determine the association between use of serotonergic
      antidepressants and perioperative blood loss and transfusion in orthopedic
      surgical patients. METHODS: A retrospective follow-up study, using routinely
      collected hospital and pharmacy data, was conducted among all orthopedic patients
      undergoing surgery from January 1, 1999, through December 31, 2000. The actual
      blood transfusion requirements and blood loss during surgery were assessed.
      Patients were divided into 3 groups for comparison: users of serotonergic
      antidepressants, users of nonserotonergic antidepressants, and nonusers of
      antidepressants. The Medical Ethics Committee approved the study protocol, and
      informed consent was obtained from all patients or their legal relatives.
      RESULTS: A total of 520 subjects with evaluable data participated in the study.
      The risk of blood transfusion almost quadrupled for the serotonergic
      antidepressant group as compared with the nonusers (adjusted odds ratio, 3.71;
      95% confidence interval, 1.35-10.18). Patients using nonserotonergic
      antidepressants had no increased risk (odds ratio, 0.74; 95% confidence interval,
      0.10-5.95). CONCLUSIONS: Use of serotonergic antidepressants is associated with
      an increased risk of bleeding and subsequent need for blood transfusion during
      orthopedic surgery. The bleeding could be attributed to inhibition of serotonin
      mediated platelet activation.

PMID- 14581257
TI  - The impact of dedicated medication nurses on the medication administration error
      rate: a randomized controlled trial.
AB  - BACKGROUND: Concerns about hospital medication safety mount as the pace of new
      drug releases accelerates. METHODS: We performed a randomized study at 2
      hospitals (A and B) to examine whether the medication administration error rate
      could be decreased by having "dedicated" nurses focus exclusively on
      administering drugs. "Medication nurses," after receiving a brief review course
      on safe medication use, were responsible solely for drug delivery for up to 18
      patients each. "General nurses," who did not attend the course, provided
      comprehensive care, including drug delivery, for 6 patients each. A direct
      observation technique was used to record drug errors, process-variation errors,
      and total errors. RESULTS: At both hospitals combined, the total error rate was
      15.7% for medication nurses and 14.9% for general nurses (P<.84). Comparing
      hospitals, the total error rate for medication nurses at hospital B was
      significantly higher than it was at hospital A (19.7% vs 11.2%; P<.04). At
      hospital A, there was a significantly lower error rate for medication nurses than
      for general nurses in the surgical units (P<.01) but no significant differences
      in total errors comparing nurse types in the medical units (P<.77). CONCLUSIONS:
      This trial suggests that use of dedicated medication nurses does not reduce
      medication error rates. However, subgroup analysis indicates that medication
      nurses might be useful in some settings. The differences in findings at the 2
      hospitals and their differences in medication-use processes reinforce the concept
      that medication errors are usually related to systems design issues.

PMID- 14581258
TI  - Effects of lifestyle on hemostasis, fibrinolysis, and platelet reactivity: a
      systematic review.
AB  - The pathophysiology of atherothrombosis in cardiovascular disease is complex and
      multifactorial. No doubt, lifestyle habits such as exercise, smoking, diet, and
      alcohol consumption may have significant influence on cardiovascular disease. As
      the hemostatic system is assuming an increasingly prominent role in the
      pathogenesis and progression of atherovascular diseases, this review evaluates
      the effects of lifestyle habits (or lifestyle modifications) on blood
      coagulation, fibrinolysis, and platelet reactivity.

PMID- 14581259
TI  - Definition of acute pyelonephritis vs the urosepsis syndrome.

PMID- 14581260
TI  - Anti-inflammatory effects of alcohol.

PMID- 14581261
TI  - Possible differences between fibrates in pharmacokinetic interactions with
      statins.

PMID- 14581262
TI  - Does the evidence for anemia treatment support a survival benefit?

PMID- 14581263
TI  - Depression and adverse drug reactions.

PMID- 14581265
TI  - Cancer research: joint planning for the future.

PMID- 14581264
TI  - Prospective studies are required prior to revision of perioperative transfusion
      guidelines.

PMID- 14581266
TI  - Antigen- and/or immune-driven lymphoproliferative disorders.

PMID- 14581267
TI  - Progress in the development and acquisition of anticancer agents from marine
      sources.

PMID- 14581268
TI  - Late local recurrences in a randomised trial comparing conservative treatment
      with total mastectomy in early breast cancer patients.
AB  - BACKGROUND: A randomised trial was conducted comparing wide lumpectomy and breast
      irradiation with modified radical mastectomy. As the follow-up was long (mean
      duration 22 years), we analysed the variation in the effect of treatment over
      time. PATIENTS AND METHODS: The trial included 179 patients with a breast cancer
      measuring </=2 cm at macroscopic examination. Eighty-eight patients had breast
      conserving surgery and radiotherapy, and 91 underwent mastectomy. All patients
      had axillary dissection. The analyses were based on Cox models with time
      dependent treatment effects. RESULTS: The effect of treatment on death or
      metastasis did not vary with time. The risk of local recurrence was lower during
      the first 5 years for the breast-conserving surgery group as compared with the
      mastectomy group, but higher after 5 years (P = 10(-4) for a different treatment
      effect over time). Similar results were found in a database including 1847
      patients with small breast tumours at diagnosis. In this analysis, late breast
      recurrences were also more frequent in the breast-conserving surgery group and
      this treatment effect was greater among younger patients (</=40 years at the time
      of diagnosis). CONCLUSIONS: Late breast recurrences were more frequently observed
      in younger patients treated with breast-conserving treatment compared with those
      submitted to mastectomy. These results require confirmation in other randomised
      studies so that younger patients with early breast cancer can receive adequate
      counselling and so that a more stringent long-term follow-up policy can be
      adopted when breast-conserving treatment is planned.

PMID- 14581269
TI  - Phase II trial combining docetaxel and doxorubicin as neoadjuvant chemotherapy in
      patients with operable breast cancer.
AB  - BACKGROUND: This study was conducted to assess the antitumour activity of
      docetaxel in combination with doxorubicin for neoadjuvant therapy of patients
      with breast cancer. PATIENTS AND METHODS: Forty-eight women were treated with
      intravenous doxorubicin 50 mg/m(2) over 15 min followed by a 1-h infusion of
      docetaxel 75 mg/m(2) every 3 weeks for six cycles. Dexamethasone or prednisolone
      premedication was allowed. Granulocyte colony-stimulating factor was not allowed
      as primary prophylaxis. The primary end point was the pathologically documented
      complete response rate (pathological response). RESULTS: The mean relative dose
      intensity calculated for four or more cycles was 0.99 for doxorubicin and 0.99
      for docetaxel. Overall, the pathological response rate was 13%. There were 11
      complete and 29 partial clinical responses for an overall response rate of 85%
      [95% confidence interval (CI) 75% to 95%] in the evaluable population (n = 47).
      Disease-free and overall survival rates were 85% (95% CI 71% to 94%) and 96% (95%
      CI 85% to 99%), respectively, after a median follow-up of 36.6 months. Grade 3/4
      neutropenia was observed in 65% of patients and 17% reported grade 4 febrile
      neutropenia. CONCLUSIONS: Docetaxel and doxorubicin is an effective and well
      tolerated combination in the neoadjuvant therapy of breast cancer. Future
      controlled trials are warranted to investigate the best schedules and to
      correlate response with biological factors.

PMID- 14581270
TI  - A trial-based cost-effectiveness analysis of letrozole followed by tamoxifen
      versus tamoxifen followed by letrozole for postmenopausal advanced breast cancer.
AB  - BACKGROUND: Third-generation aromatase inhibitors are being considered as an
      alternative to tamoxifen as first-line therapy for advanced breast cancer. These
      newer therapies are more expensive, and will gain greater acceptance if they can
      demonstrate cost-effectiveness. METHODS: Life table analyses are used to compare
      the costs and benefits [life years gained and quality-adjusted life years (QALYs)
      gained] of treating postmenopausal women with advanced breast cancer with first
      line letrozole (with the option of second-line tamoxifen) compared with first
      line tamoxifen (with the option of second-line letrozole). Patient-level data
      from a large clinical trial describes the effectiveness of the therapy options,
      clinicians estimate resource usage and utility values are obtained from the
      literature. RESULTS: The mean cost of providing first- and second-line hormonal
      therapy is pound 4765 if letrozole is the first-line therapy and pound 3418 if
      tamoxifen is provided first (a difference of pound 1347). However, patients
      receiving letrozole as first-line therapy gain an additional 0.228 life years, or
      0.158 QALYs. The cost-effectiveness analysis found that first-line hormonal
      therapy with letrozole gains additional life years at a cost of pound 5917,
      whilst the cost per additional QALY gained is pound 8514. CONCLUSION: The
      strategy of letrozole as first-line hormonal therapy not only provides an
      opportunity for extending and improving patient's quality of life, but also is
      highly cost-effective compared with other generally accepted medical treatments.

PMID- 14581271
TI  - Oral vinorelbine in combination with cisplatin: a novel active regimen in
      advanced non-small-cell lung cancer.
AB  - BACKGROUND: A phase II trial of alternating i.v. and oral vinorelbine in
      combination with cisplatin was designed to determine the response rate, safety
      profile, progression-free survival, overall survival and quality of life (QoL) in
      advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Fifty-six
      chemotherapy-naive patients received cisplatin 100 mg/m(2) and i.v. vinorelbine
      25 mg/m(2) on day 1, followed by oral vinorelbine 60 mg/m(2) on days 8, 15 and
      22, every 28 days. RESULTS: After an independent review, the response rate was
      33% [95% confidence interval (CI) 20% to 46%]. Median progression-free and
      overall survival were 5.5 months (95% CI 3.7-6.4) and 8.9 months (95% CI 8.8
      11.7), respectively. The most frequent hematological toxicities were neutropenia
      (grade 3-4 in 73% of patients) and anemia (grade 3-4 in 11% of patients). Grade 3
      4 infections and non-hematological toxicities occurred occasionally. QoL for lung
      cancer related symptoms was stable or improved. CONCLUSIONS: The efficacy and
      safety of the alternating vinorelbine schedule (i.v. on day 1, oral on days 8, 15
      and 22) in combination with cisplatin in advanced NSCLC are similar to those of
      the standard regimen using exclusively i.v. vinorelbine, whereas ease of
      administration and patient comfort may favor the novel approach.

PMID- 14581272
TI  - Prospective randomised phase II study of docetaxel versus paclitaxel administered
      weekly in patients with non-small-cell lung cancer previously treated with
      platinum-based chemotherapy.
AB  - BACKGROUND: Docetaxel and paclitaxel have activity in the second-line treatment
      of non-small-cell lung cancer (NSCLC), and can be administered as weekly
      schedules. This phase II randomised study was designed to test the efficacy and
      toxicity of both taxanes in patients with NSCLC previously treated with platinum
      based chemotherapy. PATIENTS AND METHODS: Patients (n = 71) with documented NSCLC
      were randomised to receive docetaxel (n = 35 patients; 36 mg/m(2)) or paclitaxel
      (n = 36 patients; 80 mg/m(2)) as a 1 h weekly infusion for 6 weeks followed by a
      2-week rest. The cycles were repeated until disease progression or non-acceptable
      toxicities occurred. RESULTS: Treatment achieved partial response of one versus
      five patients, median time-to-progression of 74 versus 68 days, and overall
      survival of 184 versus 105 days, with docetaxel and paclitaxel, respectively. The
      most common non-haematological toxicities were (docetaxel versus paclitaxel):
      grade 3/4 pulmonary toxicity in seven versus one patient; grade 2/3 diarrhoea in
      nine versus five; and grade 3/4 haematological toxicities occurred in two versus
      four patients. There were no treatment-related deaths. CONCLUSIONS: Docetaxel and
      paclitaxel administered weekly have discrete efficacy in patients with NSCLC
      previously treated with platinum-based chemotherapy. The higher non
      haematological toxicity of docetaxel, particularly pulmonary toxicity and
      diarrhoea, is of concern and warrants further investigation.

PMID- 14581273
TI  - Sequential transarterial chemoembolization and percutaneous acetic acid injection
      therapy versus repeated percutaneous acetic acid injection for unresectable
      hepatocellular carcinoma: a prospective study.
AB  - BACKGROUND: Transarterial chemoembolization (TACE) and percutaneous acetic acid
      injection (PAI) are effective treatments for hepatocellular carcinoma (HCC). We
      have conducted a prospective study to compare the efficacy of sequential TACE and
      PAI (TACE-PAI) versus repeated PAI therapy for HCC. PATIENTS AND METHODS: A total
      of 108 HCC patients with tumor size </=5 cm were enrolled. Fifty-three patients
      were treated with TACE-PAI and 55 patients were treated with PAI alone. RESULTS:
      Objective responses were achieved in 72 of 80 nodules (90%) in the TACE-PAI group
      compared with 51 of 62 nodules (82%) in the PAI group (P = 0.217) during 24 +/-
      10 months of follow-up. Patients in the TACE-PAI group had a significantly lower
      cumulative tumor recurrence rate from the treated nodule (P = 0.004) or newly
      developed tumor elsewhere in liver (P = 0.010). Complete tumor necrosis in large
      (3-5 cm) HCCs was more frequently encountered in the TACE-PAI group (64% versus
      37%; P = 0.034). There was no significant survival difference between the two
      groups with small (</=3 cm) HCC (P = 0.569), whereas PAI therapy was an
      independent poor prognostic predictor [relative risk 3.0 (95% confidence interval
      1.2-7.6); P = 0.017] in the large HCC group. CONCLUSIONS: Sequential therapy with
      TACE and PAI is superior to repeated PAI alone for patients with large HCC.

PMID- 14581274
TI  - Therapy and survival after recurrence of Ewing's tumors: the Rizzoli experience
      in 195 patients treated with adjuvant and neoadjuvant chemotherapy from 1979 to
      1997.
AB  - BACKGROUND: Many papers have reported the results achieved with combined therapy
      for Ewing's tumors, but little is known about the treatment and outcome of those
      30-40% of patients who relapse. PATIENTS AND METHODS: In a retrospective study,
      we evaluated 195 patients with Ewing's tumors treated at our institution from
      1979 to 1997 with chemotherapy, radiotherapy, surgery or combined therapies after
      recurrence. RESULTS: A second complete remission was achieved in only 26 patients
      (13.3%); 12 relapsed again and died of the tumor. The 5-year post-relapse event
      free survival and overall survival were 9.7% and 13.8%, respectively; both of
      which were significantly better for patients who had relapsed >/=2 years after
      the beginning of the first treatment (14.3% versus 2.5%; P <0.001) and for
      patients who relapsed with only lung metastases (14.5% versus 0.9%; P <0.0005).
      In terms of treatment, patients treated with surgery or radiotherapy, alone or in
      combination with chemotherapy, had better survival rates than patients treated
      with chemotherapy alone (15.4% versus 0.9%; P <0.0001). CONCLUSIONS: The outcome
      of Ewing's tumor patients who relapse after combined treatment is very poor.
      However, these patients may be divided into two groups: those that can be cured
      with traditional treatments (late relapse and/or only lung metastases), and a
      second group of patients (early relapses with metastases in lungs and/or other
      sites) who gain no benefit from traditional therapies. For the latter group,
      multicenter studies are needed to evaluate new strategies of treatment.

PMID- 14581275
TI  - Paclitaxel for anthracycline-resistant AIDS-related Kaposi's sarcoma: clinical
      and angiogenic correlations.
AB  - BACKGROUND: Murine data indicate that angiogenesis is central to the
      aetiopathogenesis of Kaposi's sarcoma (KS). Therefore, we measured angiogenic
      cytokines and growth factors in patients with AIDS-related KS during treatment
      with both antiretrovirals and second-line paclitaxel chemotherapy. Cytokines
      measured included tumour necrosis factor-alpha (TNF-alpha), basic fibroblast
      growth factor (bFGF), vascular endothelial growth factor (VEGF) and the
      interleukins IL-2, -6 and -12. PATIENTS AND METHODS: Enzyme-linked immunosorbent
      assays (ELISAs) were carried out to measure plasma cytokine levels in 17 patients
      with AIDS-related KS who had progressed within 6 months of receiving liposomal
      anthracyclines and were treated with paclitaxel 100 mg/m(2) every 2 weeks.
      Measurements were carried out before progression, at commencement and at the
      completion of paclitaxel. RESULTS: The objective response rate to paclitaxel was
      71% (95% confidence interval 60% to 81%). In 17 patients with AIDS-related KS, we
      observed eight partial responses and four complete responses. Patients with AIDS
      Clinical Trial Group stage T1 disease had higher plasma VEGF (P = 0.05) and lower
      plasma TNF-alpha levels (P = 0.05) than patients with earlier stage T0 KS. There
      were no correlations between plasma cytokines (bFGF, VEGF, TNF-alpha, and IL-2,-6
      and -12) and the CD4 and CD8 cell counts or HIV-1 RNA viral load. Response to
      paclitaxel was associated with a fall in plasma IL-6 levels (P = 0.04) but no
      change in other cytokines. There were no significant changes in CD4, CD8,
      CD16/56, CD19 cell counts and HIV-1 viral loads during chemotherapy. CONCLUSIONS:
      Angiogenic cytokines may correlate with KS disease extent but not with cellular
      immune function or HIV viraemia. Response to paclitaxel therapy correlates with a
      fall in plasma IL-6 levels and recent data indicate this may be a surrogate
      marker of KS-associated herpesvirus viral load. Overall, clinical response in KS
      correlates poorly with known angiogenic cytokines.

PMID- 14581277
TI  - Autologous stem cell transplantation for nasal NK/T-cell lymphoma: a progress
      report on its value.
AB  - Nasal NK/T-cell lymphoma is an Epstein-Barr virus-related, highly aggressive but
      localized disease in Orientals. The median survival is <1 year. Here, we update
      our experience on 18 patients treated with autologous stem cell transplantation
      (ASCT). Two patients died of mucositis and septicemia during ASCT. Relapse
      occurred in nine cases, including six local relapses. Compared with patients
      treated in remission, all patients treated in active or disseminated disease died
      of early relapse. Within this cohort, there was no significant survival
      difference between patients treated in first (CR1, n = 7) or second (CR2, n = 5)
      complete remissions. However, among consecutive cases analyzed, the patients
      receiving ASCT at CR1 showed a trend towards better overall survival compared
      with historical matched controls (P = 0.064). Disease relapse beyond 6 months was
      not seen after ASCT. Our retrospective data suggest that ASCT in CR1 is a viable
      consolidation therapy for local-stage NK/T lymphoma, but a randomized trial is
      needed to prove any definite survival benefit. For patients with relapsed,
      refractory or extranasal disease, early consideration for allogeneic
      transplantation and alternative therapy may be warranted.

PMID- 14581276
TI  - Beneficial effect of high-dose chemotherapy in multiple myeloma patients with
      unfavorable prognostic features.
AB  - It has been established that high-dose chemotherapy (HDT) improves the
      therapeutic outcome of patients with multiple myeloma (MM) as compared with
      standard-dose therapy (SDT); however, little is known about the impact of HDT on
      different prognostic groups of MM patients. We therefore compared the survival
      times of 77 patients with previously untreated MM who were enrolled in HDT
      regimens with those of 64 similar patients <65 years old, who would be eligible
      for HDT but were treated by SDT. Overall, HDT was superior to SDT with respect to
      achievement of complete remissions (28% versus 2%; P <0.0001) and improvement of
      progression-free survival (PFS) (30.2 versus 21.2 months; P = 0.01) as well as
      overall survival (OS) (median 54.9 versus 49.4 months; P = 0.048). According to
      the chromosome 13q14 status as determined by fluorescence in situ hybridization
      and serum levels of beta(2)-microglobulin (beta(2)M), MM patients were separated
      into a standard-risk group (normal chromosome 13q14 and beta(2)M </=4 mg/l) and a
      high-risk group (deletion of chromosome 13q14 and/or beta(2)M >4 mg/l). Among
      patients of the high-risk group, both PFS (26.4 versus 10.7 months; P = 0.004)
      and OS times (40 versus 23 months; P = 0.05) were longer in patients receiving
      HDT compared with patients treated by SDT. In the standard-risk group, PFS and OS
      times were not significantly different between HDT patients and SDT patients.
      Results of this retrospective analysis suggest that the beneficial effects of HDT
      are greater in MM patients with high-risk features than in patients with absence
      of such poor prognostic indicators.

PMID- 14581278
TI  - Folate intake and risk of oral and pharyngeal cancer.
AB  - BACKGROUND: Diet has been recognised as having a role in the aetiology of oral
      and pharyngeal cancer, and dietary factors may account for 10-15% of cases in
      Europe. Folate deficiency has been linked to risk of several cancers, but has not
      been studied adequately with respect to oral cancer. PATIENTS AND METHODS: This
      case-control study, conducted in Italy and French-speaking Switzerland, included
      749 patients with incident cancer of the oral cavity and pharynx, and 1772
      hospital controls with acute, non-neoplastic conditions. The interviews used a
      validated food frequency questionnaire. Odds ratios (OR) and 95% confidence
      intervals (CI) were estimated using multiple logistic regression. RESULTS: The
      ORs were 0.68 (95% CI 0.52-0.88) for the intermediate tertile and 0.53 (95% CI
      0.40-0.69) for the highest tertile of dietary folate intake, compared with the
      lowest tertile. No heterogeneity was found in strata of gender, age, methionine
      intake or alcohol consumption. The combined OR for low-folate and high-alcohol
      intake versus high-folate and low-alcohol intake was 22.3 (95% CI 13.1-38).
      CONCLUSIONS: Our study supports a protective role of folate against oral and
      pharyngeal carcinogenesis. Compared with low folate intake, a consistent
      reduction in risk was already observed from intermediate levels of intake,
      suggesting that cancer risk may be related to relative folate deficiency.

PMID- 14581279
TI  - Phase I clinical study of infusional 5-fluorouracil with oxaliplatin and
      gemcitabine (FOG regimen) in patients with solid tumors.
AB  - BACKGROUND: The aim of this study was to determine the maximum tolerated dose,
      recommended phase II dose (RPTD) and toxicities of the FOG regimen (infusional 5
      fluorouracil, oxaliplatin, gemcitabine). PATIENTS AND METHODS: Patients with
      advanced solid tumors were treated in an accelerated titration scheme. 5
      Fluorouracil was administered intravenously at 200 mg/m(2)/day for 14 days and
      repeated every 21 days (one cycle). Gemcitabine was administered on days 1 and 8
      over 30 min at 450-650 mg/m(2). Oxaliplatin was administered on day 1 over 2 h at
      85-130 mg/m(2). For cycles 1, 3 and beyond, gemcitabine followed oxaliplatin; for
      cycle 2, gemcitabine preceded oxaliplatin. RESULTS: Forty-five and 39 patients
      were assessable for toxicity and response, respectively. Cycle 1 dose-limiting
      toxicities (DLT) included neutropenia, thrombocytopenia and diarrhea. No DLT was
      observed in cycle 1 at the first four dose levels (DL). At DL-5, two of four
      (50%) patients experienced DLT in cycle 1. Expanding DL-4, nine of 26 (35%)
      patients experienced DLT in cycle 1. Because recurrent grade 3 toxicities were
      observed in three of six (50%) patients at DL-3, DL-2 was considered the RPTD. At
      the RPTD, three patients had a partial response (response rate 23%). CONCLUSIONS:
      The RPTD for the 5-fluorouracil-oxaliplatin-gemcitabine combination is
      200/100/450 mg/m(2). This novel regimen has demonstrated activity in advanced
      solid tumors and merits further investigation.

PMID- 14581280
TI  - Alopecia in a premenopausal breast cancer woman treated with letrozole and
      triptorelin.

PMID- 14581281
TI  - Absence of chemotherapy-induced alopecia with paclitaxel in a case of
      hypothyroidism: case report.

PMID- 14581282
TI  - High incidence of severe hand-foot syndrome during capecitabine-docetaxel
      combination chemotherapy.

PMID- 14581283
TI  - Oxygen in the rehabilitation of patients with chronic obstructive pulmonary
      disease: an old tool revisited.

PMID- 14581284
TI  - Tumor necrosis factor and lung edema clearance: the tip of the iceberg?

PMID- 14581285
TI  - Genomics made functional in ventilator-associated lung injury.

PMID- 14581286
TI  - What to learn from decision analysis of diagnosis and treatment of ventilator
      associated pneumonia?

PMID- 14581287
TI  - Taking a peep at the upper airways.

PMID- 14581288
TI  - Redox active agents in inflammatory lung injury.

PMID- 14581289
TI  - Chemoreflex drive and the dynamics of ventilation and gas exchange during
      exercise at hypoxia.
AB  - We tested the hypothesis that the promotion of hypoxic ventilatory responsiveness
      (HVR) and/or hypercapnic ventilatory responsiveness (HCVR) mostly acting on the
      carotid body with a changing work rate can be attributed to faster hypoxic
      ventilatory dynamics at the onset of exercise. Eleven subjects performed a
      cycling exercise with two repetitions of 6 minutes while breathing at FIO(2) =
      12%. The tests began with unloaded pedaling, followed by three constant work
      rates of 40%, 60%, and 80% of the subject's ventilatory threshold at hypoxia.
      Reference data were obtained at the 80% ventilatory threshold work rate during
      normoxia. Using three inhaled 100% O(2) breath tests, a comparison of hypoxia and
      normoxia revealed an augmentation of HVR in hypoxia, which then significantly
      increased proportionally with the increase in work rate. In contrast, HCVR using
      three inhaled 10% CO(2) breath tests was unaffected by the difference in work
      rate at hypoxia but did exceed its level at normoxia. The decrease in the half
      time of hypoxic ventilation became significant with an increase in work rates and
      was significantly lower than at normoxia. Using a multiregression equation, HVR
      was found to account for 63% of the variance of hypoxic ventilatory dynamics at
      the onset of exercise and HCVR for 9%. O(2) uptake on-kinetics and off-kinetics
      under hypoxic conditions were significantly slower than under normoxic
      conditions, whereas they were not altered by the changing work rates at hypoxia.
      These results suggest that the faster hypoxic ventilatory dynamics at the onset
      of exercise can be mostly attributed to the augmentation of HVR with an increase
      in work rates rather than to HCVR. Otherwise, O(2) uptake dynamics are affected
      by the lower O(2), not by the changing work rates under hypoxic conditions.

PMID- 14581290
TI  - Saving the breath condensate approach.

PMID- 14581291
TI  - Carboxylated osteocalcin levels in cystic fibrosis.

PMID- 14581292
TI  - Improvement of endothelial dysfunction by selective estrogen receptor-alpha
      stimulation in ovariectomized SHR.
AB  - Both known estrogen receptors, ERalpha and ERbeta, are expressed in blood
      vessels. To gain further insight into the role of ERalpha in a functional
      setting, we investigated the effect of the novel highly selective ERalpha agonist
      Cpd1471 on vascular reactivity in ovariectomized spontaneously hypertensive rats
      (SHR). After ovariectomy or sham operation, 12-week-old female SHR received
      either 17beta-estradiol (E2, 2 microg/kg body wt per day), the selective ERalpha
      agonist Cpd1471 (30 microg/kg body wt per day), or placebo. Acetylcholine-induced
      endothelium-dependent vasorelaxation was significantly blunted in aortas from
      ovariectomized rats (Rmax, 53%+/-3% versus sham, 79%+/-2%; P<0.001). Treatment
      with E2 or Cpd1471 significantly augmented acetylcholine-induced relaxation in
      ovariectomized rats (Rmax, 70%+/-2%; resp, 73%+/-2%). Endothelium-independent
      relaxation induced by sodium nitroprusside was not different among the four
      groups. The contractile response induced by the nitric oxide (NO) synthase
      inhibitor Nomega-nitro-l-arginine, an index of basal NO formation, was
      significantly lower in ovariectomized rats compared with sham-operated animals
      (53+/-2% versus 77%+/-5%; P<0.01) and was normalized by both E2 (70%+/-2%) and
      Cpd1471 (70%+/-3%). Aortic endothelial NO synthase (eNOS) expression and
      phosphorylation of the vasodilator-stimulated phosphoprotein, an index of NO/cGMP
      signaling, was reduced in ovariectomized SHR and normalized by E2 and Cpd1471. In
      SHR after ovariectomy, endothelium-dependent NO-mediated vasorelaxation and eNOS
      expression are attenuated. The novel selective ERalpha agonist Cpd1471 prevented
      these pathophysiological changes to a similar extent as E2. Thus, the
      pharmacological principle of selective ERalpha activation mediates positive
      vascular effects.

PMID- 14581293
TI  - Ac-SDKP reverses cardiac fibrosis in rats with renovascular hypertension.
AB  - N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is a natural substrate for the N
      terminal active site of angiotensin-converting enzyme (ACE). We previously
      reported that Ac-SDKP prevented cardiac fibrosis in rats with renovascular or
      aldosterone-salt hypertension. However, it is not clear whether Ac-SDKP reverses
      cardiac fibrosis in hypertension, nor the mechanism(s) involved. In the present
      study, we tested the hypothesis that Ac-SDKP reversal of hypertension-induced
      cardiac fibrosis involves a decrease in transforming growth factor-beta (TGF
      beta) and/or connective tissue growth factor (CTGF). In 2-kidney, 1-clip (2K-1C)
      hypertensive rats, Ac-SDKP at 400 or 800 microg/kg per day SC was started 8 weeks
      after hypertension and cardiac fibrosis were established and was continued for 8
      weeks. Left ventricular (LV) collagen in rats with 2K-1C plus vehicle at 8 and 16
      weeks after clipping was similar but higher than in the sham group (P<0.05). Ac
      SDKP at 400 and 800 microg/kg per day, which increased plasma Ac-SDKP 2- and 5
      fold, respectively, reversed the increase in LV collagen in a dose-dependent
      manner. The mechanism by which Ac-SDKP reverses LV fibrosis does not appear to
      depend on ACE inhibition by Ac-SDKP, since we found that Ac-SDKP at various doses
      did not affect blood pressure responses to exogenous angiotensin I or bradykinin.
      However, Ac-SDKP reversed the increase in LV TGF-beta and CTGF compared with rats
      with 2K-1C plus vehicle (P<0.005). We concluded that in hypertension, Ac-SDKP
      reverses cardiac fibrosis, perhaps due in part to a decrease in TGF-beta and CTGF
      in the heart.

PMID- 14581294
TI  - Adiposity is related to gender differences in impaired stress-induced pressure
      natriuresis.
AB  - The purpose of this study was to determine if there are gender differences in
      stress-induced pressure natriuresis and to examine the effects of adiposity on
      these differences. The subjects were 151 boys and 141 girls 15 to 18 years of age
      who underwent a 5-hour stress protocol (2-hour prestress, 1-hour stress, 2-hour
      poststress) after being brought into similar levels of sodium balance. The gender
      by-condition interaction was significant for systolic and diastolic blood
      pressure (P=0.001 for both), and the effect of condition was significant for
      sodium excretion (P=0.001). Systolic blood pressure was higher for boys
      throughout the protocol (P=0.001 for each) and correlated with body mass index at
      each condition (range in r=0.28 to 0.35; P<0.001 for each). Hemodynamically, in
      boys body mass index was correlated with cardiac output during stress (r=0.23;
      P=0.006), which was correlated with systolic blood pressure (r=0.21; P=0.01).
      With respect to natriuresis, body mass index was inversely correlated with sodium
      excretion during stress (r=-0.22; P=0.008) and positively correlated with
      angiotensin II in a subsample of boys (n=89: r=0.31; P=0.003). The inverse
      correlation between angiotensin II and sodium excretion during stress approached
      significance (r=-0.17; P<0.06). Similar results were not observed for girls. In
      conclusion, gender differences in stress-induced pressure natriuresis appear to
      be related to the influence of adiposity on both blood pressure and natriuresis.

PMID- 14581295
TI  - Reactive oxygen species in the vasculature: molecular and cellular mechanisms.
AB  - Accumulating evidence indicates that reactive oxygen species (ROS) play major
      roles in the initiation and progression of cardiovascular dysfunction associated
      with diseases such as hyperlipidemia, diabetes mellitus, hypertension, ischemic
      heart disease, and chronic heart failure. ROS produced by migrating inflammatory
      cells as well as vascular cells (endothelial cells, vascular smooth muscle cells,
      and adventitial fibroblasts) have distinct functional effects on each cell type.
      These include cell growth, apoptosis, migration, inflammatory gene expression,
      and matrix regulation. ROS, by regulating vascular cell function, can play a
      central role in normal vascular physiology, and can contribute substantially to
      the development of vascular disease.

PMID- 14581296
TI  - Hypertension, blood pressure, and heart rate variability: the Atherosclerosis
      Risk in Communities (ARIC) study.
AB  - Dysregulation of the autonomic nervous system has been implicated in the
      development of hypertension. Heart rate variability is a noninvasive tool to
      quantitatively estimate cardiac autonomic activity and has been used to document
      decreased cardiac autonomic activity in hypertension. The ability of decreased
      heart rate variability to predict incident hypertension has not been well
      studied, and there are no studies of whether hypertension leads to changes in
      heart rate variability. We investigated the temporal sequence linking
      hypertension, blood pressure, and heart rate variability in a population-based
      cohort of 11 061 individuals aged 45 to 54 years at baseline. Individuals with
      hypertension had decreased heart rate variability at baseline, and this
      association was present across the full blood pressure range. Among 7099
      individuals without hypertension at baseline, low heart rate variability
      predicted greater risk of incident hypertension over 9 years of follow-up. The
      hazard ratio (95% confidence interval [CI]) for the lowest compared with the
      highest quartile of the standard deviation of normal-to-normal R-R intervals was
      1.24 (95% CI, 1.10-1.40), for the root mean square of successive differences in
      normal-to-normal R-R intervals was 1.36 (95% CI, 1.21-1.54), and for R-R interval
      was 1.44 (95% CI, 1.27-1.63). Over 9 years, there was no measurable difference in
      the rate of change in heart rate variability among those with and without
      hypertension, although the differences in heart rate variability at follow-up
      were smaller than those at baseline. These findings thus support the thesis that
      the autonomic nervous system is involved in the development of hypertension, yet
      suggest that differences in the autonomic profile of hypertensives and
      normotensives do not increase with time.

PMID- 14581297
TI  - Cardiac hypertrophy is associated with decreased eNOS expression in angiotensin
      AT2 receptor-deficient mice.
AB  - Angiotensin II receptors play an essential role in cardiovascular physiology and
      disease. The significance of angiotensin type II (AT2) receptors in cardiac
      disease still remains elusive. Thus, we tested in gene-targeted mice whether AT2
      receptors modulate cardiac function and remodeling after experimental myocardial
      injury. To generate myocardial infarcts of reproducible size, a cryolesion was
      generated at the free wall of the left ventricle of wild-type mice (Agtr2+/Y) and
      mice carrying a deletion of the AT2 receptor gene (Agtr2-/Y). Postinjury
      remodeling was followed up for 4 weeks after cryoinjury. The cryoprocedure led to
      an increased heart weight/body weight ratio and heart weight/tibia length ratio
      in AT2-deficient mice compared with control mice. Morphometric analysis revealed
      a significant increase in myocyte cross-sectional area after cardiac injury
      (infarct vs sham Agtr2+/Y, +53%; vs Agtr2-/Y, +95%). Expression of endothelial
      nitric oxide synthase (eNOS) was significantly lower in hearts from Agtr2-/Y than
      from Agtr2+/Y mice. eNOS downregulation was accompanied by a decrease in cardiac
      cGMP levels in Agtr2-/Y mice. In isolated murine cardiomyocytes, angiotensin II
      induced eNOS expression through AT2 receptors, and inhibition of NO production by
      NG-nitro-l-arginine methyl ester abolished the antihypertrophic effect of AT2 on
      cardiac myocytes. Our results demonstrate in a genetic mouse model that
      angiotensin II AT2 receptors exert an antihypertrophic effect in cardiac
      remodeling after myocardial cryoinjury and link the expression of cardiac eNOS to
      AT2 receptor activation.

PMID- 14581298
TI  - Talk failures: food and fair trade.

PMID- 14581302
TI  - Use of antiretrovirals in newborns.

PMID- 14581303
TI  - Opioids and chronic pain.

PMID- 14581304
TI  - Opioids and chronic pain.

PMID- 14581306
TI  - Children and second-hand smoke.

PMID- 14581307
TI  - Evaluation of a community-based inner-city disease management program for
      postmyocardial infarction patients: a randomized controlled trial.
AB  - BACKGROUND: Disease management programs (DMPs) that use multidisciplinary teams
      and specialized clinics reduce hospital admissions and improve quality of life
      and functional status. Evaluations of cardiac DMPs delivered by home health
      nurses are required. METHODS: Between August 1999 and August 2000 we identified
      consecutive patients admitted to hospital with elevated cardiac enzymes. Patients
      who agreed were randomly assigned to participate in a DMP or to receive usual
      care. The DMP included 6 home visits by a cardiac-trained nurse, a standardized
      nurses' checklist, referral criteria for specialty care, communication with the
      family physician and patient education. We measured readmission days per 1000
      follow-up days for angina, congestive heart failure (CHF) and chronic obstructive
      pulmonary disease (COPD); all-cause readmission days; and provincial claims for
      emergency department visits, physician visits, diagnostic or therapeutic services
      and laboratory services. RESULTS: We screened 715 consecutive patients admitted
      with elevated cardiac markers between August 1999 and August 2000. Of those
      screened 71 DMP and 75 usual care patients met the diagnostic criteria for
      myocardial infarction, were eligible for visits from a home health nurse and
      consented to participate in the study. Readmission days for angina, CHF and COPD
      per 1000 follow-up days were significantly higher for usual care patients than
      for DMP patients (incidence density ratio [IDR] = 1.59, 95% confidence interval
      [CI] 1.27-2.00, p < 0.001). All-cause readmission days per 1000 follow-up days
      were significantly higher for usual care patients than for DMP patients (IDR =
      1.53, 95% CI 1.37-1.71, p < 0.001). The difference in emergency department
      encounters per 1000 follow-up days was significant (IDR = 2.08, 95% CI 1.56-2.77,
      p < 0.001). During the first 25 days after discharge, there were significantly
      fewer provincial claims submitted for DMP patients than for usual care patients
      for emergency department visits (p = 0.007), diagnostic or therapeutic services
      (p = 0.012) and laboratory services (p = 0.007). INTERPRETATION: The results
      provide evidence that an appropriately developed and implemented community-based
      inner-city DMP delivered by home health nurses has a positive impact on patient
      outcomes.

PMID- 14581308
TI  - Nature and severity of physical harm caused by child abuse and neglect: results
      from the Canadian Incidence Study.
AB  - BACKGROUND: Despite growing public concern about child maltreatment, the scope
      and severity of this significant public health issue remains poorly understood.
      This article examines the nature and severity of the physical harm associated
      with reports of child maltreatment documented in the Canadian Incidence Study of
      Reported Child Abuse and Neglect (CIS). METHODS: The CIS collected information
      directly from child welfare investigators about cases of reported child abuse or
      neglect. A multistage sampling design was used to track child-maltreatment
      investigations conducted at selected sites from October to December 1998. The
      analyses were based on the sample of 3780 cases in which child maltreatment was
      substantiated. RESULTS: Some type of physical harm was documented in 18% of
      substantiated cases; most of these involved bruises, cuts and scrapes. In 4% of
      substantiated cases, harm was severe enough to require medical attention, and in
      less than 1% of substantiated cases, medical attention was sought for broken
      bones or head trauma. Harm was noted most often in cases of physical abuse
      compared to other forms of maltreatment. INTERPRETATION: Rates of physical harm
      were lower than expected. Current emphasis on mandatory reporting, abuse
      investigations and risk assessment may need to be tempered for cases in which
      physical harm is not the central concern.

PMID- 14581309
TI  - Studying child abuse and neglect in Canada: we are just at the beginning.

PMID- 14581310
TI  - Recommendations for the management of dyslipidemia and the prevention of
      cardiovascular disease: summary of the 2003 update.

PMID- 14581311
TI  - Tailoring therapy to best suit ST-segment elevation myocardial infarction:
      searching for the right fit.

PMID- 14581312
TI  - Rehabilitation medicine: introduction to the series.

PMID- 14581313
TI  - Rehabilitation medicine: 1. Autonomic dysreflexia.
AB  - Autonomic dysreflexia is an acute syndrome of excessive, uncontrolled sympathetic
      output that can occur in patients who have had an injury to the spinal cord
      (generally at or above the sixth thoracic neurologic level). It is caused by
      spinal reflex mechanisms that remain intact despite the patient's injury, leading
      to hypertension. This review describes the clinical features of autonomic
      dysreflexia, its common causes (most frequently stimulation of the lower urinary
      tract) and a recommended approach to treatment. The condition can nearly always
      be managed successfully, but prompt recognition is essential--without treatment
      there may be dire consequences, including death.

PMID- 14581314
TI  - Latent tuberculosis: revised treatment guidelines.

PMID- 14581315
TI  - ACE inhibition in stable coronary artery disease.

PMID- 14581316
TI  - Cat naps: an elderly woman with recurrent syncope.

PMID- 14581321
TI  - Military dangles big bonuses in bid to attract debt-weary med students.

PMID- 14581322
TI  - Failure of WTO talks bleak news for health of world's poor.

PMID- 14581324
TI  - Manitoba kills cardiac care unit, consolidates services at single site.

PMID- 14581326
TI  - MDs call for new safety features after death in school bus crash.

PMID- 14581327
TI  - More than half of MDs under age 35 now using PDAs.

PMID- 14581328
TI  - More countries hoping to copy Spain's organ-donation success.

PMID- 14581333
TI  - Pathobiology, prognosis, and targeted therapy for renal cell carcinoma:
      exploiting the hypoxia-induced pathway.
AB  - Historically, clinical factors have been used as prognostic markers for patients
      with renal cell carcinoma (RCC). Recent advances in the understanding of the
      pathogenesis, behavior, and molecular biology of RCC have paved the way for
      developments that may enhance early diagnosis, better predict tumor prognosis,
      and improve survival for RCC patients. This report reviews the molecular
      mechanisms of the hypoxia-induced pathway that play an essential role in
      angiogenesis, glycolysis, and apoptosis of common cancers and may be responsible
      for the ability of the cancers to adapt to a hypoxic environment and also for
      their resistance to radiation and chemotherapy. The hypoxia-induced pathway has
      been linked genetically to RCC through the von Hippel-Lindau tumor suppressor
      gene, which is inactivated in a majority of clear cell RCCs. Therefore, RCC is a
      particularly attractive clinical model to exploit the hypoxia-induced pathway for
      new therapeutic interventions. von Hippel-Lindau, hypoxia inducible factor
      1alpha, carbonic anhydrase IX, vascular endothelial growth factor, and other
      important members of the hypoxia-induced gene family, provide new molecular
      targets for diagnosis, prognosis, and immunotherapy of RCC.

PMID- 14581334
TI  - Targeted anti-interleukin-6 monoclonal antibody therapy for cancer: a review of
      the rationale and clinical evidence.
AB  - Interleukin (IL)-6, a pleiotropic cytokine with varied systemic functions, plays
      a major role in inflammatory processes. It modulates the transcription of several
      liver-specific genes during acute inflammatory states, particularly C-reactive
      protein, and controls the survival of normal plasmablastic cells. In addition, IL
      6 has been implicated in hematopoiesis as a cofactor in stem cell amplification
      and differentiation. This article is the first review of clinical studies in the
      1990s with anti-IL-6 monoclonal antibodies (mAbs) in the treatment of patients
      with cancer and related lymphoproliferative disorders. In six clinical studies of
      mAbs to IL-6 with BE-8 or CNTO 328 in patients with multiple myeloma, renal cell
      carcinoma, and B-lymphoproliferative disorders, anti-IL-6 mAb treatment decreased
      C-reactive protein levels in all patients. In most patients, levels decreased
      below detectable limits. The antibodies were well tolerated, and no serious
      adverse effects were observed in the vast majority of studies. The fact that anti
      IL-6 mAb therapy decreased the incidence of cancer-related anorexia and cachexia
      may also be useful in the treatment of cancer patients.

PMID- 14581335
TI  - Ectopic human chorionic gonadotropin beta secretion by epithelial tumors and
      human chorionic gonadotropin beta-induced apoptosis in Kaposi's sarcoma: is there
      a connection?
AB  - Since it was first claimed in 1995 that human chorionic gonadotropin (hCG)
      inhibits HIV-associated Kaposi's sarcoma (KS), focus has been lost on
      establishing a credible hypothesis to explain a novel action ascribed to hCG,
      which is, after all, a pregnancy hormone. After 7 years, no real progress has
      been made, and there remains no consensus as to which component of hCG
      preparations is responsible for inducing apoptosis of HIV-associated KS. It would
      certainly seem apparent that many basic experiments on hCG species have been
      overlooked in the studies that have been published. Furthermore, the much wider
      literature concerning the association of hCG with promoting oncogenesis has been
      ignored. This review puts into context the numerous studies on hCG, HIV
      associated KS, and oncogenesis.

PMID- 14581336
TI  - Risk and prognosis of central nervous system leukemia in patients with
      Philadelphia chromosome-positive acute leukemias treated with imatinib mesylate.
AB  - PURPOSE: In patients with acute leukemias, a lymphoid phenotype, the presence of
      a Philadelphia chromosome (Ph), and inadequate central nervous system (CNS)
      directed prophylactic therapy are risk factors for CNS involvement. Imatinib
      mesylate has promising single-agent antileukemic activity in patients with
      advanced Ph(+) acute leukemias. It was the aim of this analysis to determine the
      incidence of, and risk factors associated with, meningeal leukemia during
      imatinib monotherapy. STUDY DESIGN: We analyzed 107 consecutive patients with
      relapsed or refractory Ph(+) acute lymphoid leukemia (ALL; n = 65) or chronic
      myeloid leukemia blast crisis (n = 42) who were enrolled in successive Phase II
      trials of single-agent imatinib and who did not receive routine prophylactic
      intrathecal chemotherapy. RESULTS: CNS leukemia developed in 13 of 107 patients
      (12%) and was associated primarily with a lymphoid or bilineage phenotype (12 of
      78; 15%) and with imatinib refractory Ph(+) ALL (5 of 19; 26%). Meningeal
      leukemia did not occur among patients who received prior prophylactic cranial
      irradiation. The median survival with combined CNS and systemic disease was 108
      days (range, 58-141), with no patient surviving long term. In contrast, two of
      three patients with exclusively meningeal leukemia achieved prolonged molecular
      remissions with intrathecal chemotherapy, cranial irradiation, and continued
      imatinib. CONCLUSIONS: Patients with Ph(+) ALL are at considerable risk of
      meningeal leukemia during imatinib monotherapy and should routinely receive CNS
      prophylaxis. Although the prognosis with combined meningeal and systemic relapse
      is dismal, patients with an isolated meningeal relapse may still achieve
      sustained remissions. The optimal type of CNS-directed treatment and the extent
      of protection afforded by prophylactic cranial irradiation remain to be defined.

PMID- 14581337
TI  - Pharmacokinetic study of cisplatin and infusional etoposide phosphate in advanced
      breast cancer with correlation of response to topoisomerase IIalpha expression.
AB  - PURPOSE: There is substantial interpatient variability in etoposide
      pharmacokinetics. Pharmacokinetic adjustment to specific plasma concentrations
      may make it possible to define a therapeutic plasma concentration and relate drug
      target expression in the tumor to response. This study evaluated the combination
      of cisplatin with a prolonged infusion of etoposide phosphate (EP) in advanced
      breast cancer and correlated response to topoisomerase II expression.
      EXPERIMENTAL DESIGN: Eligible patients, previously treated with an anthracycline,
      received 60 mg/m(2) cisplatin, followed by a 5-day infusion of EP. Plasma
      etoposide levels were measured on days 2 and 4 of each cycle with adjustment of
      the infusion rate to achieve an initial target etoposide concentration of 2 micro
      g/ml or 1.5 micro g/ml. Primary tumor blocks were stained by immunohistochemistry
      for topoisomerase IIalpha and beta. RESULTS: Thirty-six patients, treated in
      three consecutive cohorts, received 145 cycles of chemotherapy. Targeting plasma
      etoposide concentration reduced interpatient pharmacokinetic variability (32% and
      62% of patients, respectively, within 10% of target concentration on days 2 and
      4; cycle 1). Significant hematological toxicity (89% of patients with at least
      one episode of grade III/IV neutropenia, 64% of patients with at least one
      episode of grade III/IV thrombocytopenia) was observed. Thirty-nine percent of
      patients achieved a partial response, and 19% had stable disease for at least 3
      months. The median time to tumor progression was 4 months, with a median survival
      of 11 months. Topoisomerase IIalpha expression was significantly higher (P <
      0.001) in responding patients compared with those with stable or progressive
      disease. There was no difference in topoisomerase IIbeta expression between
      groups. CONCLUSION: Cisplatin and infusional EP is an active, but intensive,
      schedule in heavily pretreated patients with breast cancer. Clinical response
      correlates with tumor topoisomerase IIalpha expression.

PMID- 14581338
TI  - Studies of apurinic/apyrimidinic endonuclease/ref-1 expression in epithelial
      ovarian cancer: correlations with tumor progression and platinum resistance.
AB  - PURPOSE: A crucial step in the DNA base excision repair pathway involves the
      cleavage of an apurinic/apyrimidinic site by an apurinic/apyrimidinic
      endonuclease (APE). The major APE in mammalian cells is APE/ref-1, a
      multifunctional enzyme that acts not only as a DNA repair enzyme but as a redox
      modifying factor for a variety of transcription factors. The purpose of this
      study is to determine whether APE/ref-1 expression differs with ovarian cancer
      progression and metastasis and in platinum-resistant disease. EXPERIMENTAL
      DESIGN: Ovarian tissue sections were obtained from the Cooperative Human Tissue
      Network for studies of APE/ref-1 expression and the metastatic process and from
      our institutional Department of Pathology for studies of APE/ref-1 expression and
      platinum resistance. Tissue microsections from formalin-fixed, paraffin-embedded
      specimens of epithelial ovarian cancers were stained using a monoclonal antibody
      to APE/ref-1 followed by standard immunohistochemical techniques. Slides were
      then analyzed for the percentage of positively staining nuclei as well as
      staining intensity using a blinded coding system. RESULTS: All epithelial ovarian
      cancers expressed APE/ref-1. There were no significant differences in the
      percentage or intensity of nuclear staining in primary tumors from patients with
      early- versus advanced-stage disease or in primary tumors versus metastasis from
      patients with advanced disease. Both platinum-sensitive and platinum-refractory
      tumors demonstrated a range from minimal to high intensity staining nuclei with a
      median value of 2+ staining on a scale of 0-3+. The median value for the
      percentage of nuclei involved was 70% in the platinum-sensitive group and 90% in
      the platinum-refractory group (P = 0.118). CONCLUSIONS: APE/ref-1 expression is
      ubiquitous among epithelial ovarian cancers and is unaltered with the metastatic
      process. APE/ref-1 expression does not appear to differ between platinum
      sensitive and platinum-refractory ovarian cancers and thus is not a useful
      biomarker for platinum resistance. Combined with evidence that APE/ref-1
      expression and function may not be equivalent in all cell types and tissues,
      future work will investigate APE/ref-1 as a potential therapeutic target.

PMID- 14581339
TI  - A training-testing approach to the molecular classification of resected non-small
      cell lung cancer.
AB  - PURPOSE: RNA expression patterns associated with non-small cell lung cancer
      subclassification have been reported, but there are substantial differences in
      the key genes and clinical features of these subsets casting doubt on their
      biological significance. EXPERIMENTAL DESIGN: In this study, we used a training
      testing approach to test the reliability of cDNA microarray-based classifications
      of resected human non-small cell lung cancers (NSCLCs) analyzed by cDNA
      microarray. RESULTS: Groups of genes were identified that were able to
      differentiate primary tumors from normal lung and lung metastases, as well as
      identify known histological subgroups of NSCLCs. Groups of genes were identified
      to discriminate sample clusters. A blinded confirmatory set of tumors was
      correctly classified by using these patterns. Some histologically diagnosed large
      cell tumors were clearly classified by expression profile analysis as being
      either adenocarcinoma or squamous cell carcinoma, indicating that this group of
      tumors may not be genetically homogeneous. High alpha-actinin-4 expression was
      identified as highly correlated with poor prognosis. CONCLUSIONS: These results
      demonstrate that gene expression profiling can identify molecular classes of
      resected NSCLCs that correctly classifies a blinded test cohort, and correlates
      with and supplements standard histological evaluation.

PMID- 14581340
TI  - TERC identified as a probable target within the 3q26 amplicon that is detected
      frequently in non-small cell lung cancers.
AB  - PURPOSE: Cell lines derived from non-small cell lung cancers (NSCLCs) revealed
      frequent high-level gains of chromosomal DNA at 3q23-q29 when examined by
      comparative genomic hybridization (CGH). Within this amplicon, a minimal common
      region of amplification in lung tumors had been mapped to 3q26 by earlier
      studies. The aim of the present work was to identify specific targets of the 3q26
      amplification in NSCLCs. EXPERIMENTAL DESIGN: We examined genomic alterations in
      19 NSCLC cell lines (10 derived from squamous cell carcinomas and 9 from
      adenocarcinomas) by using CGH and fluorescence in situ hybridization. We
      determined amplification and expression levels of four candidates (EVI1, TERC,
      SNO, and PIK3CA) in those cell lines and also in 25 primary NSCLC tumors. Because
      the TERC gene encodes the RNA component of human telomerase, we examined
      telomerase activity by the telomeric repeat amplification protocol (TRAP) assay.
      RESULTS: Copy numbers of EVI1 and TERC increased more than those of SNO and
      PIK3CA in our panel of NSCLC cell lines. Significant correlation between
      amplification and expression levels was observed only for TERC (P = 0.006),
      however, among these four candidate genes. Expression of TERC was also up
      regulated in 24 (96%) of 25 primary NSCLC tumors compared with their nontumorous
      counterparts (P = 0.0001), and elevated expression of TERC was associated with
      high levels of telomerase activity (P = 0.048). CONCLUSIONS: TERC is a likely
      target of the 3q26 amplification, and, therefore, may be a useful biomarker for
      diagnosis and an attractive, novel target for molecular therapy of NSCLC.

PMID- 14581341
TI  - Confocal microscopy for real-time detection of oral cavity neoplasia.
AB  - PURPOSE: The goal of this study was to characterize features of normal and
      neoplastic oral mucosa using reflectance confocal microscopy. EXPERIMENTAL
      DESIGN: Oral cavity biopsies were acquired from 17 patients at the Head and Neck
      Clinic of The University of Texas M. D. Anderson Cancer Center who were
      undergoing surgery for squamous cell carcinoma within the oral cavity.
      Reflectance confocal images were obtained at multiple image plane depths from
      biopsies within 6 h of excision. After imaging, biopsies were fixed in 10%
      formalin and submitted for routine histological examination. Reflectance confocal
      images were compared with histological images from the same sample to determine
      which tissue features contribute to image contrast and can be potentially imaged
      using in vivo confocal microscopy. RESULTS: Confocal images were successfully
      acquired from 15 biopsy pairs from 17 patients. Depth-related changes in cell
      diameter and nuclear density were observed at multiple anatomical sites within
      the oral cavity. In squamous cell carcinomas, densely packed, pleomorphic tumor
      nuclei could be visualized with distinct differences in nuclear density and
      morphology distinguishable between confocal images of neoplastic and
      nonneoplastic oral cavity. Other features of noncancerous and cancerous oral
      tissue that could be identified in the confocal images included areas of
      inflammation, fibrosis, muscle fibers, and salivary glands. CONCLUSIONS: Our
      results support the potential for this tool to play a significant role in the
      clinical evaluation of oral lesions, real-time identification of tumor margins,
      and monitoring of response to therapeutic treatment.

PMID- 14581342
TI  - Relationships between plasma insulin-like growth factor-I and insulin-like growth
      factor binding protein-3 and second breast cancer risk in a prevention trial of
      fenretinide.
AB  - PURPOSE: High circulating insulin-like growth factor (IGF) -I and/or low IGF
      binding protein (IGFBP) -3 levels are associated with increased breast cancer
      risk in unaffected premenopausal women. We determined whether IGF-I and IGFBP-3
      predict second breast cancer risk, and whether their changes during fenretinide
      explain observed reductions in second breast cancer in women </=50 years of age.
      EXPERIMENTAL DESIGN: Within a Phase III trial, we measured baseline and 1-year
      levels of IGF-I, IGFBP-3, and their ratio in 302 subjects on fenretinide and 220
      controls who provided plasma samples. The prognostic effect of IGF-I and IGFBP-3,
      and the surrogate effect of IGF-I during fenretinide were assessed by Cox models
      after 9.4 years. RESULTS: Among controls, high IGF-I and low IGFBP-3 were
      associated with elevated second breast cancer risk [top versus bottom tertile,
      IGF-I, hazard ratio (HR) = 1.94, 95% confidence interval (CI), 0.87-4.31, P =
      0.105; and IGFBP-3, HR = 0.40, 95% CI, 0.18-0.93, P = 0.033]. Fenretinide induced
      reductions of IGF-I, IGFBP-3, and IGF-I:IGFBP-3 of 8% (95% CI, 2-12%; P = 0.004),
      3% (95% CI, 1-5%; P = 0.002), and 5% (95% CI, 0-10%; P = 0.050), respectively.
      Second breast cancer risk was reduced by 39% (HR = 0.61; 95% CI, 0.40-0.94; P =
      0.026). The percentage of treatment effect explained by IGF-I and IGF-I:IGFBP-3
      reductions were 4.8% (95% CI, 0.8-28.9%) and 3.1% (95% CI, 0.5-20.8%),
      respectively. CONCLUSIONS: Fenretinide induced a moderate reduction of IGF-I,
      which marginally explains observed cancer risk reductions in women </=50 years of
      age. In this age group high IGF-I and particularly low IGFBP-3 levels predict
      second breast cancer risk.

PMID- 14581343
TI  - Inactivation of cyclin D2 gene in prostate cancers by aberrant promoter
      methylation.
AB  - PURPOSE: Loss or abnormal expression of Cyclin D2, a crucial cell cycle
      regulatory gene, has been described in human cancers; however, data for prostate
      tumors are lacking. We investigated the epigenetic silencing of Cyclin D2 gene in
      prostate cancers and correlated the data with clinicopathological features.
      EXPERIMENTAL DESIGN: Cyclin D2 promoter methylation was analyzed in 101 prostate
      cancer samples by methylation-specific PCR. In addition, we analyzed 32
      nonmalignant prostate tissue samples, which included 24 samples of benign
      disease, benign prostatic hypertrophy, or prostatitis and 7 normal tissues
      adjacent to cancer. The methylation status of Cyclin D2 was correlated with the
      methylation of nine other tumor suppressor genes published previously from our
      laboratory on the same set of samples (R. Maruyama et al., Clin. Cancer Res., 8:
      514-519, 2002). The methylation index was determined as a reflection of the
      methylated fraction of the genes examined. RESULTS: The frequency of methylation
      of Cyclin D2 promoter was significantly higher in prostate cancers (32%) than in
      nonmalignant prostate tissues (6%; P = 0.004), and it was not age related.
      Aberrant methylation was present at insignificant levels in peripheral blood
      lymphocytes (8%). We also compared methylation of cyclin D2 with methylation of
      nine tumor suppressor genes [published previously from our laboratory (R.
      Maruyama et al., Clin. Cancer Res., 8: 514-519, 2002)] studied in the same set of
      samples. The concordances between methylation of Cyclin D2 and the methylation of
      RARbeta, GSTP1, CDH13, RASSF1A, and APC were statistically significant, whereas
      methylation of P16, DAPK, FHIT, and CDH1 were not significant. The differences in
      methylation index between malignant and nonmalignant tissues for all 10 genes
      were statistically significant (P < 0.0001). Among clinicopathological
      correlations, the high Gleason score group had significantly greater methylation
      frequency of Cyclin D2 (42%; P = 0.004). Although the high preoperative serum
      prostate-specific antigen (PSA) group did not have significantly greater
      methylation frequency, methylation of Cyclin D2 had higher mean PSA value. Also,
      the prostate cancers in the high Gleason score group had high mean values of PSA.
      CONCLUSIONS: Our results indicate that methylation of Cyclin D2 in prostate
      cancers correlates with clinicopathological features of poor prognosis. These
      findings are of biological and potential clinical importance.

PMID- 14581344
TI  - ZD1839 (Iressa) modifies the activity of key enzymes linked to fluoropyrimidine
      activity: rational basis for a new combination therapy with capecitabine.
AB  - PURPOSE: The efficacy of new oral fluoropyrimidines, including capecitabine, is
      improved in cells expressing high levels of thymidine phosphorylase (TP) and low
      levels of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase. We used
      a human head and neck cancer cell line (CAL33) to examine the influence of cell
      cycle modifications on TS, TP, and dihydropyrimidine dehydrogenase activity.
      EXPERIMENTAL DESIGN: Cells were exposed to the epidermal growth factor receptor
      tyrosine kinase inhibitor ZD1839 (Iressa(2)) and 5'-deoxy-5-fluorouridine (5'
      DFUR), alone and in combination, for up to 96 h, and modifications in cell cycle,
      enzyme activity, and gene expression were examined. RESULTS: ZD1839 (24- to 72-h
      exposure) markedly reduced proliferation and caused a rapid increase in G(0)-G(1)
      and a decrease in S phase; a 40-fold decrease in TS activity at 24 h and a 2.5
      fold increase in TP activity at 48 h were observed. A significant link between TP
      activity and expression was observed (r(2) = 0.98; P = 0.0068). Additional
      investigations pointed out an increased cellular production of 5-fluorouracil
      anabolites from 5'-DFUR when cells were preincubated with ZD1839. Dose-effect
      curves of ZD1839 and 5'-DFUR, alone and in combination, were examined.
      Combination indices for ZD1839 + 5'-DFUR were 0.58 +/- 0.1 and 0.63 +/- 0.1 for
      50% survival and 25% survival, respectively. Additional investigations pointed
      out an increased cellular production of 5-fluorouracil anabolites from 5'-DFUR
      when cells were preincubated with ZD1839. CONCLUSIONS: These data demonstrate a
      strong synergistic interaction between ZD1839 and 5'-DFUR when ZD1839 is applied
      before or concurrently with 5'-DFUR. Such a drug combination would have two
      advantages: (a) the theoretical advantage of tumor selectivity of epidermal
      growth factor receptor-targeted therapy; and (b) the practical advantage of a
      combination therapy that could be administered p.o.

PMID- 14581345
TI  - Human telomerase reverse transcriptase-specific T-helper responses induced by
      promiscuous major histocompatibility complex class II-restricted epitopes.
AB  - An effective tumor vaccine may require the induction of both CTL and T-helper
      (Th) cell responses against tumor-associated antigens. Human telomerase reverse
      transcriptase (hTERT) is highly expressed in >85% of cancer cells and thus is a
      potential target for tumor vaccines. We therefore sought to identify promiscuous
      Th epitopes in hTERT, which can be presented by more than one MHC class II
      allele. Each of 10 peptides derived from hTERT that were predicted to bind to MHC
      class II molecules was found to be able to induce primary human T-cell responses
      in vitro. We then established CD4(+) T-cell clones specific for these peptides
      and found that only hTERT(766) (LTDLQPYMRQFVAHL)-specific CD4(+) Th cells were
      effective in recognizing naturally processed hTERT antigen. We further found that
      the naturally processed epitopes hTERT(766) and hTERT(672) (which was identified
      previously) were promiscuous and capable of inducing CD4(+) T-cell responses in
      the context of several commonly found HLA-DR alleles, including DR1, DR7, and
      DR15 for hTERT(672), and DR4, DR11, and DR15 for hTERT(766). We further
      demonstrated that immunization of humanized HLA-DR4 transgenic mice with
      hTERT(766) peptide elicited antigen-specific Th responses that can recognize the
      antigenic peptides derived from hTERT protein and various hTERT-positive tumors,
      such as breast cancer, melanoma, and leukemia. It was also shown that T-cell
      precursors specific for the naturally processed epitopes are part of the T-cell
      repertoires in healthy donors and prostate cancer patients. Thus, these
      promiscuous, naturally processed Th epitopes in hTERT could be used to develop
      improved cancer vaccines through the simultaneous stimulation of CTL and Th cells
      against a broad spectrum of hTERT-positive tumors.

PMID- 14581346
TI  - A randomized, double-blind, placebo-controlled trial of the effects of rofecoxib,
      a selective cyclooxygenase-2 inhibitor, on rectal polyps in familial adenomatous
      polyposis patients.
AB  - PURPOSE: The aim of this study was to examine the effect of a specific
      cyclooxygenase-2 inhibitor, rofecoxib, on rectal polyps in familial adenomatous
      polyposis patients. EXPERIMENTAL DESIGN: This was a randomized, double-blind,
      placebo-controlled study of the efficacy and safety of rofecoxib in the rectum.
      Initially, 21 patients were assigned randomly in a 1:1 ratio to receive either 25
      mg rofecoxib once a day or a placebo p.o. for 9 months. Patients underwent
      endoscopy at the beginning of the study and then every 3 months thereafter. We
      reviewed the videotapes to measure the number and size of polyps in the same area
      throughout the study period in each individual patient. RESULTS: The polyp
      number, measured as the percentage of change from the baseline values, was
      significantly decreased in the rofecoxib group at 3, 6, and 9 months. At 9
      months, the polyp number in the rofecoxib group decreased by 6.8% from the
      baseline values, whereas that in the placebo group increased by 3.1%. The 9.9%
      difference between the rofecoxib and placebo groups was statistically significant
      (P = 0.004). At 9 months, the rofecoxib group showed a significant reduction from
      the baseline in polyp size as compared with the placebo group (-16.2% versus
      1.5%; P < 0.001). There was no statistically significant increase in the
      incidence of any adverse events in treatment with rofecoxib compared with placebo
      (P = 0.922). CONCLUSIONS: In this study, once-daily treatment with 25 mg
      rofecoxib, a cyclooxygenase 2-specific inhibitor, significantly decreased the
      number and size of rectal polyps in familial adenomatous polyposis patients.

PMID- 14581347
TI  - A phase I, pharmacokinetic, and biological study of the farnesyltransferase
      inhibitor tipifarnib in combination with gemcitabine in patients with advanced
      malignancies.
AB  - PURPOSE: To assess the feasibility of administering tipifarnib, an oral
      nonpeptidomimetic competitive inhibitor of farnesyltransferase, in combination
      with gemcitabine and recommend doses for disease-directed clinical trials. The
      study also sought to identify drug-drug pharmacokinetic interactions, evaluate
      effects on protein farnesylation, and seek preliminary evidence for clinical
      activity. EXPERIMENTAL DESIGN: Patients with advanced solid malignancies were
      treated with tipifarnib at doses of 100, 200, and 300 mg twice daily continuously
      and 1000 mg/m(2) gemcitabine i.v. on days 1, 8, and 15 every 4 weeks. To identify
      pharmacokinetic interactions, the treatment and plasma sampling schemes were
      designed to permit comparisons of the pharmacokinetic behavior of each agent
      administered alone and together. The proportions of unfarnesylated and
      farnesylated HDJ2, a chaperone protein that undergoes farnesylation, were
      measured in peripheral blood mononuclear cells. RESULTS: Nineteen evaluable
      patients were treated with 74 courses of tipifarnib/gemcitabine (mg/mg/m(2)).
      Myelosuppression was the principal toxicity. Dose-limiting myelosuppression
      occurred in 2 of 5 patients at the 300/1000 dose level, whereas 2 of 11 evaluable
      patients at the 200/1000 dose level experienced dose-limiting toxicity. There was
      no evidence of clinically relevant pharmacokinetic interactions between
      tipifarnib and gemcitabine. Inhibition of farnesylation of HDJ2, a potential
      surrogate for Ras and/or other potentially relevant farnesylated proteins, was
      demonstrated in peripheral blood mononuclear cells at all dose levels. Partial
      responses were noted in patients with advanced pancreatic and nasopharyngeal
      carcinomas. CONCLUSIONS: On the basis of the results of this study, the
      tipifarnib/gemcitabine dose level of 200/1000 is recommended for disease-directed
      studies. At this dose level, biologically relevant plasma concentrations of
      tipifarnib that consistently inhibit protein farnesylation in vitro are achieved
      and drug-induced inhibition of protein farnesylation is measured in most
      patients.

PMID- 14581348
TI  - SU5416 plus interferon alpha in advanced renal cell carcinoma: a phase II
      California Cancer Consortium Study with biological and imaging correlates of
      angiogenesis inhibition.
AB  - PURPOSE: Vascular endothelial growth factor (VEGF) is expressed in up to 70% of
      renal cell carcinomas (RCCs) and is a rational therapeutic target. SU5416 is a
      small molecule inhibitor of VEGF-mediated signaling through Flk-1, a
      transmembrane tyrosine kinase. IFN-alpha also possesses dose- and schedule
      dependent antiangiogenic effects at doses lower than those used for RCC therapy.
      We hypothesized that SU5416 plus low dose IFN-alpha 2B (Intron-A) would result in
      a 1-year event-free survival (EFS), exceeding 20% in patients with metastatic RCC
      using the results of a randomized immunotherapy trial as historical control.
      Efficacy was correlated with serial plasma VEGF and plasminogen activator
      inhibitor-1 levels and with positron emission tomography scans. EXPERIMENTAL
      DESIGN: Thirty patients were treated with SU5416 145 mg/m(2) i.v. twice weekly
      plus Intron-A 1 million units s.c. twice daily, cycled every 6 weeks. RESULTS:
      Fifteen patients (50%) had stable disease (SD) at 12 weeks, including 1 minor
      response and 8 with progressive disease (27%). Median survival time was 10
      months, and 1-year EFS was 6% (95% confidence interval, 1-35). The most common
      grade 3 or 4 toxicities included fatigue and lymphopenia, among others. There
      were 3 on-study deaths, 2 of which were infection-related. Significant declines
      in median plasma levels of VEGF pre- and posttherapy were observed. In 5 patients
      with paired FDG and O-15 positron emission tomography scans, tumor metabolism and
      perfusion were unchanged in 3 patients with SD, increased in 1 patient with
      progression, and decreased in 1 patient with SD. CONCLUSIONS: Although SU5146
      plus low-dose IFN exhibits biological activity in RCC as evidenced by significant
      declines in serial VEGF and plasminogen activator inhibitor-1 plasma levels, the
      1-year EFS of 6% and adverse toxicity profile diminishes enthusiasm for
      additional studies with this combination in advanced RCC.

PMID- 14581349
TI  - Identification of epithelial cell adhesion molecule autoantibody in patients with
      ovarian cancer.
AB  - The epithelial cell adhesion molecule (Ep-CAM) exhibited an ovarian cancer:normal
      human ovarian surface epithelium ratio of 444. For validation studies, real-time
      quantitative PCR analysis and immunohistochemistry were performed in normal and
      malignant ovarian epithelial cell lines and tissues. To evaluate the potential of
      the Ep-CAM autoantibody as a tumor marker, we examined the amount of Ep-CAM
      autoantibody in serum samples obtained from ovarian cancer patients and normal
      controls by an ELISA. Real-time quantitative PCR analysis revealed significant
      overexpression of Ep-CAM mRNA in cancer cell lines (P < 0.001) and microdissected
      cancer tissues (P < 0.05), compared with that in cultured normal human ovarian
      surface epithelium and microdissected germinal epithelium, respectively.
      Immunolocalization of the Ep-CAM autoantibody showed that the sera of ovarian
      cancer patients expressed higher levels of Ep-CAM autoantibody than benign tumor
      patients and normal controls (P < 0.05). The levels of Ep-CAM autoantibody found
      were as follows: 0.132 in 52 patients with ovarian cancer, 0.098 in 26 cases with
      benign gynecologic disease, and 0.090 in 26 normal women. This investigation has
      shown that the Ep-CAM autoantibody was found to be associated with ovarian cancer
      and suggested that future research assessing its clinical usefulness would be
      worthwhile.

PMID- 14581350
TI  - Reactive stroma as a predictor of biochemical-free recurrence in prostate cancer.
AB  - Extensive scientific literature data point to reciprocal interactions between
      prostate stromal cells and prostate cancer cells that likely regulate tumor
      progression. To investigate whether these intratumoral-reactive stromal cells in
      human prostate cancer are predictive of survival, tumor stroma volume and
      specific stroma markers were quantitated by using tissue microarrays (index
      tumors of 847 patients), and the results were analyzed relative to the recurrence
      free survival data set for these patients. Tumor tissue was evaluated with
      Masson's trichrome stains and by immunohistochemistry with antibody probes to
      smooth muscle alpha-actin, desmin, vimentin, pro-collagen type I, and calponin.
      The relative volume of intratumor stroma (5% stroma, grade 0; 5-15%, grade 1; 15
      50%, grade 2; >50%, grade 3) and the expression index of stromal marker (staining
      intensity grade x percentage of positive cells per field) were quantitated and
      analyzed. Interpretable data were obtained from 545 patients. Statistical
      analysis of the survival data set showed that the volume of reactive stroma in
      the tumor was a significant predictor of disease-free survival. Stroma volume was
      most optimal as an independent predictor in tumors containing stroma, defined as
      Gleason 7 and lower grades. Of interest, tumors with either little to no stroma
      or tumors with abundant stroma each showed reduced recurrence-free survival. For
      specific stromal markers, reduced desmin and smooth muscle alpha-actin were
      hallmarks of cancer-associated reactive stroma relative to normal fibromuscular
      stroma. Quantitative analysis of desmin and smooth muscle alpha-actin expression
      showed both to be significant and independent predictors of recurrence-free
      survival. This is the first study to demonstrate that nonepithelial-reactive
      stroma elements in prostate cancer tumors can be used as prognostic indicators.
      These data also add to the concept that tumors are not purely epithelial and the
      tumor-reactive stroma must be considered an important biological component of the
      cancer.

PMID- 14581351
TI  - Production of interleukin 15 by human colon cancer cells is associated with
      induction of mucosal hyperplasia, angiogenesis, and metastasis.
AB  - PURPOSE: The purpose of this study was to identify a mediator produced by human
      colon cancer cells that is responsible for the induction of hyperplasia in the
      adjacent mucosa. EXPERIMENTAL DESIGN: Seventy human colon cancer surgical
      specimens were immunostained to determine the presence of cytokines that can
      induce hyperplasia in the adjacent mucosal. Human colon cancer cells with low and
      high metastatic potential were implanted into the cecal wall of nude mice. The
      resulting lesions were studied by immunohistochemistry to detect possible
      mediators of mucosal hyperplasia. RESULTS: Immunostaining of 70 colon cancer
      specimens from 70 patients suggested that mucosal hyperplasia and distant
      metastasis were associated with the expression of interleukin (IL)-15 and, to a
      lesser extent, transforming growth factor alpha. The production of IL-15 by colon
      cancer cells was not associated with the infiltration of natural killer cells
      into the tumors. Cecal tumors produced in nude mice by human colon cancer cells
      with low and high metastatic potential (KM12C and KM12SM cells, respectively)
      expressed similar levels of transforming growth factor alpha, and expression of
      IL-15 was detected only in the metastatic KM12SM cells and was associated with
      hyperplasia of the surrounding mucosa. The expression of the IL-15 receptor in
      rat intestinal epithelial cells (IEC6 cells) was confirmed by immunoblotting with
      antibodies against IL-15 receptor alpha and IL-2 receptor beta and gamma subunits
      and by a binding assay using (125)I-labeled IL-15 (K(d) = 0.011 nM). IL-15
      stimulated proliferation of the IEC6 cells, even under serum starvation.
      Treatment of IEC6 cells with IL-15 decreased doxorubicin-mediated cytotoxicity.
      In IEC6 cells treated with either IL-15- or KM12SM-conditioned medium,
      immunoblotting revealed a decrease in the production of p21Waf1, Bax, and Bak and
      an increase in the production of cyclin E, proliferating cell nuclear antigen,
      the phosphorylated active form of AKT, basic fibroblast growth factor, and
      vascular endothelial growth factor, changes associated with cell growth,
      survival, and induction of angiogenesis. CONCLUSIONS: These data indicate that IL
      15 produced by metastatic colon carcinoma cells can induce hyperplasia in the
      mucosa adjacent to colon cancer, thus contributing to angiogenesis and
      progression of the disease.

PMID- 14581353
TI  - Gene amplification in esophageal adenocarcinomas and Barrett's with high-grade
      dysplasia.
AB  - PURPOSE: The purpose of this study was to determine the frequency and overall
      contribution of specific gene amplification events in the formation of Barrett's
      adenocarcinomas. The relationship of gene amplification to clinical-pathological
      variables and its potential usefulness as a marker for early cancer detection
      were also examined. EXPERIMENTAL DESIGN: We used quantitative PCR and Southern
      blot analysis to screen 87 cases of Barrett's adenocarcinoma for the presence or
      absence of 13 distinct gene amplification events. Gene amplification was then
      examined for correlation with other amplification events and clinical variables
      (survival, stage, nodal involvement, tumor invasion, smoking history, and
      gender). Additionally, 22 specimens of Barrett's with high-grade dysplasia (HGD)
      were examined for the presence of gene amplification. RESULTS: One or more
      amplification events were present in 50 of 87 (57%) adenocarcinomas. The ERBB2
      gene was amplified in 19 of 87 (21.8%), CCNE1 in 11 of 87 (12.6%), GATA4 in 9 of
      87 (10.3%), KRAS in 9 of 87 (10.3%), EGFR in 7 of 87 (8.0%), CCND1 in 6 of 87
      (6.8%), HNF3alpha in 5 of 87 (5.7%), PIK3CA in 5 of 87 (5.7%), C-MYC in 4 of 87
      (4.6%), DYRK2 in 2 of 87 (2.3%), and AIB1, AKT1, and IGF1R were amplified in 0 of
      87 (0%) of the tumors. CCND1 amplification was found to correlate negatively with
      survival (P < 0.05). In addition, the ERBB2 amplicon positively correlated (P <
      0.05) with GATA4 amplification. Increased copy number of the ERBB2 (1 of 22),
      GATA4 (1 of 22), KRAS (2 of 22), C-MYC (1 of 22), CCNE1 (2 of 22), and CCND1 (2
      of 22) genes was also observed in one or more Barrett's adenocarcinomas with HGD.
      CONCLUSIONS: The high frequency of gene amplification in esophageal
      adenocarcinomas and HGD indicates the important role of these events in
      esophageal adenocarcinoma development. Additionally, these results underscore the
      possible usefulness of early detection approaches and chemotherapeutic strategies
      (ErbB2 and cyclin D1) targeted against amplified gene products.

PMID- 14581352
TI  - Choice of normal ovarian control influences determination of differentially
      expressed genes in ovarian cancer expression profiling studies.
AB  - PURPOSE: As with many cancers thought to be of epithelial origin, expression
      profiling studies of ovarian cancer have relied on a variety of sources of normal
      cells for comparison with tumors, including whole ovary samples (WO), ovarian
      surface epithelium (OSE) exposed to short-term culture, and immortalized OSE cell
      lines (IOSE). Our purpose was to assess the impact of the use of different types
      of normal controls on the determination of gene expression alterations in ovarian
      cancer studies. EXPERIMENTAL DESIGN: We compared the gene expression profiles
      generated on an 11,000-element cDNA microarray of OSE brushings, whole ovary
      samples, short-term cultures of normal OSE, SV40 large T antigen-immortalized OSE
      cell lines, and telomerase-immortalized OSE cell lines. The function of the
      groups as normal controls was then assessed by separate comparisons of each group
      to a set of 24 serous ovarian carcinoma samples. RESULTS: The normal groups
      formed robust, distinct clusters in hierarchical clustering and multidimensional
      scaling. The Pearson correlation coefficient for all combinations of any two of
      the groups ranged from 0.04 to 0.54, emphasizing the disparity of the groups. In
      the gene lists produced by comparing each normal group with the ovarian cancer
      samples, the majority of genes were unique to that normal-cancer comparison, with
      no gene appearing on all five lists. CONCLUSIONS: These results suggest that the
      selection of a normal control to compare with epithelial ovarian cancer samples
      in microarray studies strongly influences the genes that are identified as
      differentially expressed and complicates comparison with studies using a
      different normal control.

PMID- 14581354
TI  - Automated analysis of multiple sections for the detection of occult cells in
      lymph nodes.
AB  - PURPOSE: At present, reverse transcription (RT)-PCR against carcino-embryonic
      antigen mRNA is one of the few research tools for the detection of occult cells
      in histopathologically assessed negative lymph nodes from patients with
      colorectal cancer. The aim of this study was to investigate the suitability of
      supervised low-resolution image analysis of immunohistochemically stained
      sections as alternative. EXPERIMENTAL DESIGN: Multiple sections (n = 50) of
      regional lymph nodes from patients with colorectal cancer were
      immunohistochemically stained and analyzed by applying low-resolution image
      analysis (flatbed scanning) for semiautomated detection of cytokeratin (CK)
      positive stained cells. The sensitivity of this approach was demonstrated for 20
      patients with stage II colorectal cancer and compared with RT-PCR regarding the
      detection of clinically assessed recurrence of disease within 10 years. RESULTS:
      CK(+) cells were detected in all of the patients (n = 6; 100%) with recurrence,
      compared with five patients (83%) found positive by carcinoembryonic antigen RT
      PCR. From patients (n = 14) who did not develop a recurrence, eight (57%) had
      positive lymph nodes. In all patients with recurrence, we visually identified at
      least one group of CK(+) cells (>/==" BORDER="0">2 cells). CONCLUSIONS: Automated
      image analysis is a promising tool for the detection of occult cells in
      histopathologically negative nodes. It is potentially more sensitive but less
      specific for detecting recurrence of disease than conventional histopathology or
      RT-PCR and is particularly useful for the evaluation of sentinel nodes.
      Furthermore, it opens new ways for basic research of occult cells based on
      molecular profiling after laser-microdissection.

PMID- 14581355
TI  - Gain of distal chromosome arm 17q is not associated with poor prognosis in
      neuroblastoma.
AB  - PURPOSE: In several studies, gain of the distal long arm of chromosome 17 was
      shown to be a frequent and prognostically relevant factor in neuroblastoma, in
      addition to MYCN amplification (MNA) or 1p deletion. We asked whether this
      observation could be confirmed in a German cohort. EXPERIMENTAL DESIGN: To
      evaluate the frequency and prognostic impact of 17q gain, we investigated tissue
      samples from 193 neuroblastoma patients by the use of fluorescence in situ
      hybridization. The DNA probe (MPO) was located in distal 17q in the region of
      interest as used by several groups. To analyze the association of patients'
      outcome with the breakpoint position within 17q, we used the more proximal DNA
      probe ERBB2 in 17q21 on a selected number of cases. Gain was defined as an excess
      of 17q material compared with the chromosome 17 centromere in at least 50% of the
      analyzed tumor cells. In addition, alterations in chromosomes 1p, 3p, and 11q, as
      well as MYCN status, were determined to describe the interrelationship between
      the different parameters and to evaluate an independent prognostic influence.
      RESULTS: Gain of 17q was found in 61% of the investigated tumors. An additional
      23% displayed an excess of 17q in less than half of all cells. Gain correlated
      with stage 4 disease (P = 0.003) and with other chromosomal alterations, such as
      1p (P < 0.001), 3p (P = 0.01), 11q (P = 0.001), and MNA (P = 0.016), as well as
      with increased patient age (P = 0.01). Outcome was not different between patients
      with 17q gain compared with those without, however. A prognostic influence could
      not be delineated in all stages or in localized or in stage 4 subgroups or in the
      MYCN nonamplified patient cohort. Outcome did not differ between patients with
      additional 17q material in <10% of the cells or in >70%. Patients showing a
      breakpoint in the more proximal part of 17q could not be described as having a
      more favorable outcome compared with patients with a more distal breakpoint.
      Prognosis was poor in patients with MNA and/or 11q loss either with or without
      17q gain. A multivariate analysis including the chromosomal parameters 17q, 11q,
      and MYCN status, as well as stage, showed MYCN and 11q status (P < 0.001), but
      not 17q or stage as significant prognostic factors. CONCLUSION: Although the most
      frequent aberration in neuroblastoma to date, we found no association between 17q
      gain and an inferior prognosis in our cohort; the status of MYCN and 11q,
      however, allowed reliable prediction of patients' outcomes.

PMID- 14581356
TI  - Phenotype versus genotype in gliomas displaying inter- or intratumoral
      histological heterogeneity.
AB  - PURPOSE: Molecular classification of gliomas is becoming increasingly important
      clinically as an adjunct to histopathological diagnosis. Whereas histological
      heterogeneity of gliomas is well recognized, less is known of the relationship
      between histological heterogeneity and genetic alterations. Our objective was to
      investigate the relationship between genotype and phenotype for markers of
      potential clinical utility in histologically heterogeneous gliomas. EXPERIMENTAL
      DESIGN: We have used laser capture microdissection to sample the various
      histological phenotypes present in 42 tumors from 25 glioma cases with either
      inter- or intratumoral histological heterogeneity, and multiple simultaneous PCR
      amplification of microsatellite markers and capillary electrophoresis to
      determine allelic imbalance in chromosomes 1p, 19q, 17p, 10p, and 10q. RESULTS:
      Loss of 1p36 and 19q13 was seen only in oligodendroglial histology in 7 of 13
      oligodendrogliomas. 17p13 loss was found in 14 of 41 tumors in astrocytic,
      oligoastrocytic, oligodendroglial, and glioblastomatous histologies. Chromosome
      10 loss was seen in all of the high-grade histologies in 7 of 7 glioblastomas
      with an oligodendroglial component and in 1 of 5 low-grade oligodendroglial
      regions present within high-grade tumors. Seven tumors from 5 cases had no
      detectable losses of any markers investigated. In 13 tumors with intratumoral
      heterogeneity, identical genetic losses were present in all areas of histological
      differentiation. Additional losses were seen in some but not all of the
      histologies within 2 tumors and were associated with progression in 3 cases.
      CONCLUSIONS: The gliomas in this study were more homogeneous in their genotype
      than their histological phenotype with regions of differing histological subtype
      indistinguishable by the genetic markers investigated, supporting a monoclonal
      origin of these tumors.

PMID- 14581357
TI  - Increased expression of angiogenin in hepatocellular carcinoma in correlation
      with tumor vascularity.
AB  - PURPOSE: Neovascularization is known to be one of the major characteristics of
      human hepatocellular carcinoma (HCC). Angiogenin (ANG), originally discovered in
      a human colon cancer cell line, is a liver-derived polypeptide that shows strong
      angiogenic activity in vivo. However, the role of ANG on the development of HCC
      remains unknown. The present study was designed to examine the implication of ANG
      in the neovascularization of human HCC. EXPERIMENTAL DESIGN: Forty-one HCC
      patients who had undergone conventional celiac angiography were used in this
      study. ANG protein expression and microvessel density (MVD) in HCC specimens
      obtained by liver biopsy or surgical resection were examined by
      immunohistochemistry, and the levels were quantified by the KS-400 image
      analyzing system. ANG mRNA expression in liver tissues was evaluated by in situ
      hybridization. Serum ANG concentrations were measured by an ELISA. Survival rates
      were calculated using the Kaplan-Meier method. RESULTS: Immunohistochemistry and
      in situ hybridization showed greater increments of ANG protein expression and
      mRNA expression, respectively, in HCC tissues than in the surrounding nontumorous
      tissues. MVD within tumorous tissues increased according to dedifferentiation of
      the histological grade of HCC, showing a significant correlation (r = 0.877, P =
      0.0009) with ANG expression levels. Mean +/- SD serum ANG levels of healthy
      subjects and chronic hepatitis (CH) patients were 362.3 +/- 84.1 ng/ml and 331.9
      +/- 133.8 ng/ml, respectively, with no significant difference. Serum ANG levels
      of liver cirrhosis patients (242.4 +/- 126.9 ng/ml) were lower than those of
      healthy subjects or CH patients and decreased as the fibrosis grade advanced. In
      HCC patients, despite the cirrhotic background, serum ANG levels increased as the
      tumor vascularity increased (197.8 +/- 64.9 ng/ml for hypovascular, 326.7 +/-
      148.6 ng/ml for hypervascular, and 405.0 +/- 121.3 ng/ml for very hypervascular),
      in good accordance with histological grading, and significantly decreased (P =
      0.015) after successful treatment with transcatheter arterial embolization or
      percutaneous ethanol injection. HCC patients were conventionally divided into two
      groups according to the serum level of ANG, those with values higher than the
      mean level (332.9 +/- 143.8 ng/ml) and those with values lower than the mean,;
      the 5-year survival rate of the latter group was determined to be significantly
      higher than that in the former group. CONCLUSIONS: These results suggest that ANG
      is one of the neovascularization defining factors of HCC. Thus, measuring serum
      ANG may assist in monitoring the disease, and targeting ANG may provide a new
      strategy for treating advanced HCC.

PMID- 14581358
TI  - Retention of the p53 codon 72 arginine allele is associated with a reduction of
      disease-free and overall survival in arginine/proline heterozygous breast cancer
      patients.
AB  - PURPOSE: The arginine to proline substitution at codon 72 represents a common
      aminoacidic polymorphism of the p53 protein. Recent data suggest that p53 codon
      72 may modulate the response to cancer therapy. The aim of this study was to test
      the hypothesis that the p53 codon 72 genotype, evaluated in the tumor tissue and
      in the disease-free lymph node, is related to differences in disease-free and
      overall survival among breast cancer-affected patients. EXPERIMENTAL DESIGN: We
      assessed the p53 codon 72 genotype in DNA from disease-free lymph nodes and
      neoplastic tissues obtained from 67 women affected by breast cancer who underwent
      surgical resection at the Bologna Breast Cancer Surgical Unit from 1993 to 1995.
      RESULTS: We found that the retention of the p53 codon 72 arginine allele in the
      tumor tissue of proline/arginine heterozygous breast cancer patients is
      associated with statistically significant reduced disease-free and overall
      survivals. CONCLUSIONS: Our findings suggest that the genotyping for p53 codon 72
      locus in both the tumor tissue and in the lymph node of breast cancer patients
      could contribute to identify a subset of arginine/proline heterozygous patients
      who have a reduced survival that is associated with the specific retention of the
      arginine allele in the tumor tissue.

PMID- 14581359
TI  - Molecular detection of breast cancer cells in the peripheral blood of advanced
      stage breast cancer patients using multimarker real-time reverse transcription
      polymerase chain reaction and a novel porous barrier density gradient
      centrifugation technology.
AB  - PURPOSE: The goal of this study was to develop a molecular diagnostic assay to
      detect circulating breast cancer cells in the peripheral blood for the purpose of
      staging breast cancer. Our aim was to make available an assay that was not
      limited by the low concentration of circulating breast cancer cells and the
      background gene expression that is typically found in peripheral blood.
      EXPERIMENTAL DESIGN: In this study, we investigated the ability of two new
      technologies to significantly enhance the quantification of gene expression in
      the peripheral blood: enrichment by a novel porous barrier density gradient
      centrifugation technology; and multimarker real-time reverse transcription-PCR
      (RT-PCR). RESULTS: Using fluorescence-labeled breast cancer cells and flow
      cytometry, we show that processing peripheral blood by porous barrier density
      gradient centrifugation results in a 300-fold enrichment of breast cancer cells.
      Real-time RT-PCR analysis confirmed a concomitant reduction in background
      expression of the CK19 and MUC1 genes after enrichment. In a pilot study, porous
      barrier density gradient centrifugation and multimarker real-time RT-PCR enabled
      our laboratory to detect breast cancer-associated gene overexpression in 13 of 20
      (65%) stage IV breast cancer patients. Nine of these 14 patients overexpressed
      three or more markers. CONCLUSIONS: These results confirm the promise of such a
      molecular diagnostic assay and suggest that additional studies are needed to
      precisely define the clinical relevance.

PMID- 14581360
TI  - Effect of pesticide exposure on HER-2/neu overexpression seen in patients with
      extensive stage small cell lung carcinoma.
AB  - PURPOSE: The aim of this study was to evaluate the relationship, if any, between
      pesticide exposure and overexpression of the HER-2/neu oncoprotein in extensive
      stage small cell lung cancer (ESSCLC). EXPERIMENTAL DESIGN: The records of all
      patients with a diagnosis of ESSCLC from January 1991 through April 2001 were
      reviewed in our retrospective study. Pesticide risk (herbicide and insecticide)
      was assessed by telephone interviews using a predetermined questionnaire with
      emphasis on type of exposure, use of protective measures, and duration of
      exposure. An exposure index was calculated (h/day x days/year x years), and
      patients with an index > 2400 h were considered as exposed. HER-2/neu
      overexpression was assessed by immunohistochemistry using the Hercep test
      developed by Dako. Statistical analysis was performed using SPSS-10. RESULTS: A
      total of 193 patients (84 females and 109 males), with a mean age of 68.5 years
      (range, 42-90 years) were included in the study. Of these, 57 (29.5%) revealed
      HER-2/neu overexpression by immunohistochemistry. After adjusting for age,
      smoking, Eastern Cooperative Oncology Group score, and treatment, HER-2/neu
      overexpression was associated with a statistically significant diminished
      survival (P < 0.001; Mann-Whitney U test). We contacted 53 of 57 patients with
      overexpression and 121 of 136 patients without HER-2/neu overexpression to
      ascertain a history of pesticide exposure. Forty-one of 53 (77.4%) patients with
      HER-2/neu overexpression and 47 of the 121 patients without overexpression
      (38.8%) were exposed to pesticides. We found that patients with history of
      pesticide exposure had a higher risk of having HER-2/neu overexpression (odds
      ratio, 5.38; P < 0.01, 95% confidence interval, 2.5-11.2) CONCLUSIONS: HER-2/neu
      is overexpressed in approximately 30% patients with ESSCLC and is associated with
      decreased survival. Also, pesticide exposure seems to be related to HER-2/neu
      overexpression seen in our patient population. Future studies are needed to
      validate our findings and also to determine which pesticide(s)/pesticide
      components are actually responsible for HER-2/neu overexpression seen in ESSCLC.

PMID- 14581361
TI  - Interleukin 1 system and sex steroid receptor expression in human breast cancer:
      interleukin 1alpha protein secretion is correlated with malignant phenotype.
AB  - PURPOSE: The interleukin 1 (IL-1) system plays an important role in human
      pathology and is involved in the local control of malignant disease. However,
      little is known about its expression in breast cancer and its correlation with
      prognostic parameters such as receptor status and grading. EXPERIMENTAL DESIGN:
      The expression of IL-1alpha and other IL-1 family members was analyzed by reverse
      transcription-PCR, ELISA, and immunohistochemistry in breast cancer cell lines,
      tumor-derived fibroblasts, and breast cancer tissue biopsies and compared with
      sex steroid receptor status and grading. RESULTS: In breast cancer cell lines, IL
      1alpha and -beta gene expression was present in the phenotypically most malignant
      cell lines, whereas estrogen receptor (ER) alpha and progesterone receptor mRNA
      expression was confined to lines that exhibit a rather benign phenotype. Only the
      highly malignant receptor-negative tumor cell line MDA MB 231 expressed IL-1alpha
      protein, and none of the cell lines secreted IL-1beta. Biopsies from breast
      cancer tissue expressed various amounts of IL-1alpha, IL-1beta, and IL-1 receptor
      antagonist mRNA, but consistently high levels of IL-1tIR. IL-1alpha protein
      expression was detected in tumor cells and/or adjacent stroma in 88%, and
      epithelial protein expression was correlated with both poor differentiation (P =
      0.002; r = 0.469) and decreasing epithelial ERalpha expression (P = 0.004; r = 
      0.387). Furthermore, stromal IL-1alpha was predominant in areas with low or
      absent ERalpha protein expression in neighboring tumor epithelium (P = 0.001; r =
      -0.457). CONCLUSION: We have demonstrated the presence of a functional IL-1
      system in breast cancer and found that IL-1alpha is inversely correlated with
      local sex steroid receptor expression. We hypothesize that the unphysiological
      expression of IL-1alpha in less differentiated and ERalpha-negative tumors might
      contribute to their local invasiveness and malignant behavior.

PMID- 14581362
TI  - Deregulation of the TP53/p14ARF tumor suppressor pathway in low-grade diffuse
      astrocytomas and its influence on clinical course.
AB  - PURPOSE: The chromosome 9p21 region harbors three tumor suppressor genes,
      p14(ARF), p15(INK4b), and p16(INK4a), all of which can be targets for
      hypermethylation-associated inactivation in low-grade gliomas. p16(INK4a) and
      p15(INK4b) are critically involved in the RB1 pathway, whereas p14(ARF) acts as
      an upstream regulator of the TP53 pathway. The role of each tumor suppressor
      pathway in low-grade diffuse astrocytomas and their relationships with clinical
      behavior remain to be elucidated. EXPERIMENTAL DESIGN: We assessed the
      alterations of the RB1/CDK4/p16(INK4a)/p15(INK4b) and the TP53/MDM2/p14(ARF)
      pathways in 46 WHO grade II astrocytomas and analyzed their impact on prognosis.
      RESULTS: The TP53/MDM2/p14(ARF) pathway was altered in 32 of 46 cases (70%) by
      either TP53 mutation (25 cases) or p14(ARF) methylation (9 cases). The
      RB1/CDK4/p16(INK4a)/p15(INK4b) pathway was disrupted in 6 of 46 cases (13%) by
      either RB1 methylation (1 case), p16(INK4a) methylation (3 cases), or p15(INK4b)
      methylation or homozygous deletion (3 cases). Generally speaking, individual
      tumors thus tended to display alteration of only one component from both
      pathways. Any independently analyzed genetic alteration failed to provide
      statistically prognostic information. The alternate or simultaneous presence of
      TP53 mutation and p14(ARF) methylation emerged as a univariate predictor of a
      shorter progression-free survival (P = 0.0456) but was not statistically
      significant when age and extent of surgery were included in the analysis.
      CONCLUSIONS: Alternative disruption of the TP53/p14(ARF) pathway represents a
      frequent event in low-grade diffuse astrocytomas and correlates with an
      unfavorable clinical course. However, its value is unlikely to include prognostic
      utility that is independent of other conventional prognostic factors.

PMID- 14581363
TI  - The role of gelatinase in hepatic metastasis of colorectal cancer.
AB  - PURPOSE: To determine the role of gelatinase in the hepatic metastatic process of
      colorectal cancer, we correlated gelatinolytic activity in colorectal tumor
      tissue both to the presence of intravasated colorectal epithelial cells and to
      the formation of liver metastasis. EXPERIMENTAL DESIGN: The gelatinolytic
      activity was analyzed in tumor tissue samples from 68 colorectal cancer patients
      by using gelatin substrate zymography. The presence of intravasated colorectal
      epithelial cells was defined as detection of guanylyl cyclase C mRNA in blood
      sampled from drainage vein of a tumor-bearing colorectal segment. RESULTS: Forty
      of 68 patients were noted to have guanylyl cyclase C mRNA expression in their
      drainage venous blood. Fifteen patients were noted to have liver metastasis at
      the time of surgery, and another 15 patients developed liver metastasis during
      median follow-up period of 53 months. Either individual or total gelatinolytic
      activity in colorectal tumor tissue failed to predict the presence of
      intravasated colorectal epithelial cells in the drainage venous blood or
      formation of liver metastasis. Presence of both intravasated colorectal
      epithelial cells and high total gelatinolytic activity in colorectal tumor
      tissue, however, is a strong predictor of liver metastasis (P = 0.004).
      CONCLUSION: Our data suggested that gelatinolytic activity in colorectal tumor
      tissues may facilitate the hepatic metastatic process in the steps after
      intravasation but not during or before intravasation.

PMID- 14581364
TI  - Differential expression of the enzyme that esterifies retinol, lecithin:retinol
      acyltransferase, in subtypes of human renal cancer and normal kidney.
AB  - PURPOSE: Retinoids, a group of compounds, including vitamin A (retinol), and
      related metabolites, have been shown to regulate the growth and differentiation
      of many types of cells. IFN-alpha and either 13-cis-retinoic acid or liposomal
      all-trans retinoic acid have been used in the treatment of patients with
      metastatic renal cell carcinoma. We knew that samples from renal cell carcinomas
      contained greatly reduced levels of retinol and retinyl esters relative to
      samples from normal human kidney. This prompted us to examine the levels of LRAT
      (lecithin:retinol acyltransferase) protein in various subtypes of human kidney
      cancers relative to normal human kidney by immunohistochemistry. EXPERIMENTAL
      DESIGN: We examined 31 partial or radical nephrectomy specimens diagnosed with
      kidney tumors between 1997 and 1998. Representative paraffin-embedded tissue
      blocks from each tumor, with each containing adjacent nonneoplastic renal
      parenchyma, were used for immunohistochemical analysis with affinity purified
      antibodies to human LRAT protein. RESULTS: LRAT protein was detected at high
      levels in the epithelial cells in the tubules and the lining of Bowman's capsule
      in the glomeruli of normal, nonneoplastic kidney sections. Among the 31 tumors,
      there were 13 cases of conventional (clear cell) renal cell carcinoma (RCC;
      including 2 multilocular cystic RCCs), 7 papillary RCC, 6 chromophobe RCC, 1 RCC,
      unclassified, and 4 renal oncocytoma. All tumors showed diffuse immunoreactivity
      for LRAT. In each case, the staining was uniform throughout the tumor, with only
      minimal variation in the staining intensity between different areas. All 4 renal
      oncocytomas, 2 of 6 chromophobe RCCs, 1 conventional (clear cell) carcinoma, 1
      RCC, unclassified, and 2 conventional RCCs, which were of the multilocular cystic
      type stained strongly (3+) for LRAT. In contrast, the remaining conventional RCCs
      and the papillary RCC samples stained much less intensely for LRAT. Of the 10
      tumors that stained 3+ for LRAT in the study, 9 were either benign tumors or
      tumors with low malignant potential. CONCLUSIONS: These data show that LRAT
      expression is higher in renal tumors with an indolent biological behavior.
      Additional studies will ascertain if LRAT possesses any prognostic or therapeutic
      role in renal cancer.

PMID- 14581365
TI  - CD24 expression is a new prognostic marker in breast cancer.
AB  - PURPOSE: CD24 is expressed in hematological malignancies as well as in a large
      variety of solid tumors including breast cancer. We aimed to evaluate CD24
      protein expression in breast cancer and to correlate to clinicopathological data
      including patient survival. EXPERIMENTAL DESIGN: Primary breast carcinomas (201)
      with a mean clinical follow-up time of 53 months were immunostained using a
      monoclonal CD24 antibody (Ab-2, clone 24C02). The staining was evaluated as
      negative versus positive for statistical analysis. RESULTS: In invasive breast
      carcinomas, CD24 expression was observed in 84.6% of cases. In univariate
      survival analyses, a significant association of CD24 expression with shortened
      patient overall survival (5-year survival rate 91.9% versus 83.8%; P = 0.031; log
      rank test) and disease-free survival (5-year progression rate 88.3% versus 57.0%;
      P = 0.0008) was demonstrated. In multivariate analyses CD24, tumor grading and
      nodal status were significant prognostic parameters for shortened disease-free
      survival. CONCLUSIONS: Our data suggest that CD24 expression in primary breast
      cancer as detected by immunohistochemistry might be a new marker for a more
      aggressive breast cancer biology.

PMID- 14581366
TI  - Elevated expression of inhibitor of apoptosis proteins in prostate cancer.
AB  - PURPOSE: Inhibitor of apoptosis (IAP) family proteins are suppressors of
      apoptosis that have been implicated in apoptosis resistance in some cancers.
      Their expression and relevance to the prognosis of prostate cancer were
      investigated. EXPERIMENTAL DESIGN: The expression of four members of the IAP
      family (cellular inhibitor of apoptosis protein 1, cellular inhibitor of
      apoptosis protein 2, X chromosome-linked IAP, and survivin) was examined by
      immunohistochemistry and immunoblotting in human prostate cancers and in prostate
      tissues from transgenic mice expressing SV40 large T antigen under control of a
      probasin promoter. RESULTS: Tumor-associated elevations in the levels of all four
      IAP family members were common in prostate cancers of both humans and mice,
      suggesting concomitant up-regulation of multiple IAP family proteins. Compared
      with normal prostatic epithelium, increased IAP expression was often evident even
      in prostatic intraepithelial neoplasia lesions (carcinoma in situ), suggesting
      that deregulation of IAP expression occurs early in the pathogenesis of prostate
      cancer. IAP expression did not correlate with Gleason grade or prostate-specific
      antigen levels. CONCLUSIONS: The findings demonstrate that tumor- associated
      elevations in the expression of several IAP family proteins occur as a frequent
      and early event in the etiology of prostate cancer.

PMID- 14581367
TI  - Reduced ING1b gene expression plays an important role in carcinogenesis of non
      small cell lung cancer patients.
AB  - PURPOSE: We performed a clinical study on ING1b gene expression and p53 gene
      status in relation to p53 target genes. EXPERIMENTAL DESIGN: Eighty-eight tumors
      from surgically treated non-small cell lung cancer (NSCLC) patients were studied.
      PCR-single-strand conformational polymorphism after sequencing was performed to
      investigate ING1 and p53 gene status. Quantitative reverse transcription-PCR was
      performed to evaluate the gene expression of ING1b, p21, and bax. The results of
      p21 and bax expression were confirmed with immunohistochemistry. RESULTS: Only
      two carcinomas (2.3%) had nonmissense mutations of ING1b. Thirty-seven carcinomas
      (42.0%) had reduced ING1b gene expression. Thirty-seven carcinomas (42.0%) had
      mutations of p53. In total, 63 carcinomas (71.6%) had either reduced ING1b
      expression or mutant p53. The p21 gene expression ratio was significantly lower
      in the ING1b-reduced tumors than in the ING1b-positive tumors (P = 0.0029).
      Similarly, the bax gene expression ratio was significantly lower in the ING1b
      reduced tumors than in the ING1b-positive tumors (P < 0.0001), and it was also
      significantly lower in tumors that had either reduced ING1b expression or mutant
      p53 than in tumors that had both positive ING1b expression and wild-type p53 (P =
      0.0331). CONCLUSIONS: Reduction of ING1b gene expression was associated with
      reduced p21 and bax gene expression in NSCLCs. The present study is the first
      clinical report to confirm the positive role of ING1b in regulating p21 and bax
      gene expression. ING1b might be one of the tumor suppressor genes that could play
      a role in carcinogenesis in NSCLC patients.

PMID- 14581368
TI  - Evaluation of urinary plasminogen activator, its receptor, matrix
      metalloproteinase-9, and von Willebrand factor in pancreatic cancer.
AB  - PURPOSE: Pancreatic cancer remains a devastating problem with the majority of
      patients succumbing to death from this disease. A hallmark of pancreatic cancer
      is the loss of basement membrane that may be attributed to the action of urinary
      plasminogen activator (uPA) and matrix metalloproteinase-9 (MMP-9). These enzymes
      are also implicated in angiogenesis. uPA and microvessel density have been shown
      to be good prognostic indicators for breast and colon cancer. MMP-9 and
      microvessel density have not been investigated in pancreatic cancer. We have
      therefore investigated by immunohistochemistry: (a) frequency of uPA expression
      and its receptor uPAR and the site of synthesis of uPA by in situ hybridization
      (ISH); (b) MMP-9 and its coexpression with uPA; (c) microvessel density as
      determined by von Willebrand factor staining and its relationship to uPA and MMP
      9 expression; and (d) correlation of these parameters with survival. EXPERIMENTAL
      DESIGN: Archival paraffin sections of 27 pancreatic tumors were
      semiquantitatively investigated by immunohistochemistry using the following
      antibodies: (a) monoclonal antibodies (MAbs) uPA(1) and uPA(2) (3689 and 394,
      respectively); (b) MAb uPAR, (no. 3932); (c) MAb MMP-9 (no. 936); and (d) rabbit
      anti-F8RA/vWF. ISH was performed using a uPA cDNA. RESULTS: Both uPA antibodies
      revealed overexpression of uPA (93%) often with uniform staining of tumor cells.
      uPAR and MMP-9 showed focal staining in only 52 and 37% of tumors, respectively.
      Morphologically normal appearing ductal cells in close proximity to tumors
      overexpressed uPA in contrast to distally located normal cells (P = <0.001). uPA
      staining was also investigated in pancreatic intraepithelial neoplasia (PanIN)
      lesions. PanIN 1A/B staining for uPA was seen in 8 cases (30%), that for PanIN 2
      in 19 cases (70%), and for PanIN3 in 12 cases (44%). Lumen of microvessels in the
      tumor stroma also revealed staining of uPA in 10 cases (37%). ISH experiments
      revealed the presence of uPA mRNA not only in the cytoplasm of tumor cells but
      also in adjacent normal appearing ducts as well as in PanIN lesions. Patients
      with overexpression of uPA, uPAR, or MMP-9 had a trend toward poorer survival
      than those who did not express it. Microvessel density did not show any
      significant relationship with uPA, uPAR, and MMP-9 expression and survival.
      CONCLUSIONS: We conclude that uPA and MMP-9 are potential prognostic indicators
      in pancreatic cancer, whereas microvessel density may not be one. This study
      confirms our previous observation that uPA is made by the tumor cells themselves.
      Presence of uPA in vessels of tumor stroma suggests that uPA is in circulation,
      and its measurement and that of MMP-9 in the blood of these patients may aid in
      prognosis. Patients showing overexpression of uPA and MMP-9 have a trend toward
      shorter survival time.

PMID- 14581369
TI  - Hypoxia and differentiation in squamous cell carcinomas of the uterine cervix:
      pimonidazole and involucrin.
AB  - PURPOSE: Pimonidazole binding (hypoxia) and involucrin expression
      (differentiation) overlap extensively in squamous cell carcinomas. This study
      asks whether involucrin might serve as an endogenous marker for tumor hypoxia. A
      second question is whether differentiation affects hypoxia-inducible
      metallothionein (MT) expression in normal human epithelia and squamous cell
      carcinomas as it does in rodent epithelia. EXPERIMENTAL DESIGN: Thirty-four
      patients with squamous cell carcinoma of the uterine cervix were infused with
      pimonidazole hydrochloride solution. The next day, multiple biopsies were
      formalin-fixed, paraffin-embedded and sectioned at 4 micro m. Qualitative and
      quantitative analyses for involucrin expression, pimonidazole binding, and human
      MT-IIa mRNA expression were performed. RESULTS: No overall correlation between
      the extent of involucrin expression and pimonidazole binding was observed. The
      lack of correlation was because of heterogeneous patterns of immunostaining for
      involucrin generally related to tumor grade. Colocalized immunostaining for
      involucrin and pimonidazole binding was observed in intermediate grade tumors but
      not in well-differentiated or poorly differentiated tumors. Human MT-IIa mRNA and
      MT protein were expressed in basal lamina of normal human epithelia and in the
      proliferative rims of tumor nests. CONCLUSIONS: Colocalization of immunostaining
      for involucrin and pimonidazole binding is consistent with oxygen regulation, but
      the lack of involucrin expression in hypoxic regions of poorly differentiated
      tumors indicates that its transcriptional status with respect to hypoxia
      induction is altered by cell differentiation. The localization of MT message and
      protein in the outer rims of most tumor nests indicates that the transcriptional
      status of metallothionein is also altered by differentiation.

PMID- 14581370
TI  - Bombesin/gastrin-releasing peptide receptor: a potential target for antibody
      mediated therapy of small cell lung cancer.
AB  - PURPOSE: Bombesin/gastrin releasing peptide (BN/GRP) is a growth factor for small
      cell lung cancer (SCLC). The receptor (R) for BN/GRP is overexpressed on SCLC
      cells and other solid tumors. BN/GRP and its receptor form an autocrine loop to
      promote tumor growth. We developed a novel immunotherapeutic approach targeting
      cell surface BN/GRP-R on SCLC cells and an immune trigger molecule on host immune
      effector cells to direct immune effector cells to SCLC cells and mediate targeted
      cancer cell destruction. Targeted immunotherapy combined with chemotherapy
      enhanced cell killing. EXPERIMENTAL DESIGN: We designed a synthetic BN/GRP
      antagonist (Antag 2) and constructed a bispecific molecule (BsMol), H22xAntag 2
      (humanized monoclonal antibody) for FcgammaRI. We tested the binding of the BsMol
      to several SCLC cell lines, its ability to mediate cytotoxicity of SCLC by IFN
      gamma-activated human monocytes with chemotherapy, and BsMol-mediated
      immunotherapy in an animal model of SCLC human xenograft. RESULTS: Common
      chemotherapy (cisplatin, etoposide, and paclitaxel) inhibited thymidine uptake
      into SCLC cells in a dose-dependent pattern. Antibody-dependent cellular
      cytotoxicity mediated by the BsMol inhibited thymidine uptake into SCLC cells and
      was largely dependent on E:T cell ratio. When SCLC cells were treated with
      antibody-dependent cellular cytotoxicity followed by exposure to chemotherapy
      agents an additional 25-40% inhibition of thymidine uptake into SCLC cells was
      observed consistently. With BsMol and IFN-gamma-activated human monocytes, tumor
      burdens were reduced significantly in immunodeficient mice bearing human SCLC
      xenografts. CONCLUSIONS: Combined chemotherapy and immunotherapy targeting BN/GRP
      R with a BsMol significantly enhances targeted SCLC cell killing.

PMID- 14581372
TI  - Exisulind and related compounds inhibit expression and function of the androgen
      receptor in human prostate cancer cells.
AB  - In recent studies, we found that sulindac sulfide (SS), exisulind, CP248, and
      CP461 induce growth inhibition and apoptosis in a series of human prostate cancer
      cell lines, irrespective of cyclooxygenase expression, p53 mutations, or bcl-2
      overexpression. Exisulind also inhibited the growth of the androgen-dependent
      LNCaP human prostate cancer cell line when grown as a xenograft in nude mice.
      This study demonstrates that doses of these compounds that induce growth
      inhibition and apoptosis in LNCaP cells also cause decreased prostate-specific
      antigen (PSA) secretion and decreased cellular levels of PSA. These effects
      appear to be a result, at least in part, of inhibition of the androgen receptor
      (AR) signaling pathway because the treated cells also display decreases in the
      level of the AR protein and mRNA and inhibition of transcription of an AR
      promoter luciferase reporter in transient transfection assays. SS and exisulind
      were more effective in inhibiting the expression of PSA and the AR than CP248 or
      CP461, apparently because of differential effects of these compounds on specific
      transcription factors. These findings suggest that the growth inhibition by these
      compounds in human prostate cancer cells may be mediated, in part, by inhibition
      of AR signaling. Thus, these compounds may provide a novel approach to the
      prevention and treatment of human prostate cancer.

PMID- 14581371
TI  - Hormone-refractory breast cancer remains sensitive to the antitumor activity of
      heat shock protein 90 inhibitors.
AB  - PURPOSE: The antiestrogen tamoxifen (Tam) has been used as therapy against
      estrogen receptor (ER)-positive breast cancer for decades. Most tumors respond
      initially, but resistance frequently develops. The ER exists in a multiprotein
      complex containing the molecular chaperone heat shock protein (Hsp) 90, which is
      known to regulate the stability and activity of this receptor. Therefore, we
      investigated a ligand-independent approach to hormonal therapy that depletes
      cellular levels of the receptor by inhibiting the function of Hsp90. EXPERIMENTAL
      DESIGN: The activity of the Hsp90 inhibitor geldanamycin (GA) and its clinically
      relevant derivative, 17-allylamino-17-demethoxygeldanamycin (17AAG), was examined
      at the molecular and cellular levels using Tam-resistant MCF-7 breast cancer
      cells both in vitro and in tumor xenografts. RESULTS: The ER was depleted by GA
      in several Tam-resistant cell lines, as were other Hsp90 client proteins such as
      Akt and Raf-1. Unexpectedly, Tam inhibited ER depletion by GA but had no effect
      on destabilization of Akt or Raf-1. When SCID mice supplemented with Tam were
      treated with 17AAG, their tumors also showed no decrease in ER levels as measured
      by immunofluorescent staining and laser scanning cytometry. In these same tumors,
      however, decreased Akt and Raf-1 levels were observed. Drug administration also
      led to inhibition of tumor xenograft growth. The mechanism by which Tam inhibits
      GA-mediated ER depletion is unclear, but immunoprecipitation experiments showed
      that Tam does not inhibit the ability of GA to alter the ER-chaperone complex.
      CONCLUSIONS: Based on its ability to deplete the ER as well as other critical
      signaling molecules in Tam-resistant breast cancer, 17AAG may provide a useful
      alternative treatment for patients with recurrent, hormone-refractory breast
      cancer that should be explored further in Phase II trials. In this context,
      combined treatment with 17AAG and Tam should be avoided because Tam may inhibit
      the ability of 17AAG to deplete the ER, potentially reducing its anticancer
      activity.

PMID- 14581374
TI  - Coxsackievirus adenovirus receptor expression predicts the efficiency of
      adenoviral gene transfer into non-small cell lung cancer xenografts.
AB  - PURPOSE: Current paradigms postulate that inefficient adenoviral (Ad) gene
      transfer is a consequence of poor Coxsackievirus adenovirus receptor (CAR)
      expression in tumors in vivo. To test whether exuberant CAR expression alone is
      sufficient to mediate efficient Ad gene transfer, we compared Ad gene transfer
      efficiency in a panel of non-small cell lung cancer (NSCLC) cell model systems in
      which we systematically measured CAR expression in vitro and in vivo.
      EXPERIMENTAL DESIGN: NSCLC cells were selected for study on the basis of (a)
      differences in Ad transduction, (b) identical requirements for growth in vitro,
      (c) capacity to grow as xenografts in immunocompromised mice, and (d) similar
      amounts of alpha(v) integrin expression as measured by flow cytometry. CAR
      expression and Ad transduction profiles of these NSCLC cells were generated in
      vitro and in vivo. RESULTS: Ad transduction efficiency of NSCLC cells in vitro
      can be directly related to CAR expression at both the mRNA and protein level. CAR
      expression in vitro favorably predicts a comparable pattern of expression in
      transplanted NSCLC xenografts in vivo. Xenografts generated from NSCLC cells
      exhibiting increased CAR expression showed evidence of higher Ad gene transfer,
      although the efficiency of transduction was reduced compared with in vitro
      measurements. Thus, in NSCLC cells with high basal expression of CAR, Ad vector
      doses that enabled uniform transduction in vitro achieve a gene transfer
      efficiency ranging from 10% to 70% after a single intratumoral injection in the
      xenografts. CONCLUSIONS: These studies indicate CAR expression is predictive for
      more efficient gene transfer into NSCLC cells in vitro and in vivo but is not
      sufficient to achieve uniform transduction by Group C Ad vectors in vivo.

PMID- 14581373
TI  - Carboxylesterases expressed in human colon tumor tissue and their role in CPT-11
      hydrolysis.
AB  - PURPOSE: The purpose is to develop new analytical methods to study the expression
      profile of CPT-11 carboxylesterases and topoisomerase I in colon tumor samples
      and understand the impact of their expression on CPT-11 metabolism in
      chemotherapy. EXPERIMENTAL DESIGN: We investigated 24 colon tumors for expression
      of carboxylesterases CES1A1, CES2, CES3, hBr-3, and topoisomerase I genes by real
      time PCR and correlated the gene expression with activity assays. The relative
      abundance of the carboxylesterase isoenzymes and topoisomerase I genes was
      determined by real-time PCR. Activity assays performed on colon tumor extracts
      included CPT-11 hydrolase, 4-methylumbelliferyl acetate hydrolase, and
      topoisomerase I activity assays. Additionally, nondenaturing activity gel
      electrophoresis with activity staining showed the distribution of
      carboxylesterases. RESULTS: We detect the expression of CES1A1, CES2, and CES3
      carboxylesterase genes in human colon tumors. We were unable to detect the hBr-3
      (also called hCE-3) in human liver, colon, or brain. We find large
      interindividual variation, >/=150-fold, for both CES1A1 and CES3 genes, 23-fold
      for CES2, and 66-fold for topoisomerase I. Only CES2 gene expression correlated
      with the carboxylesterase activity assays (P < 0.01) with CPT-11 and 4
      methylumbelliferyl acetate as substrates. Nondenaturing activity gel
      electrophoresis showed that CES2 was the most predominant activity. Topoisomerase
      I gene expression significantly correlated with topoisomerase I activity (P <
      0.01) in the colon tumors, but interindividual variation was very high.
      CONCLUSIONS: We conclude that CES2 is the most abundant carboxylesterase in colon
      tumors that is responsible for CPT-11 hydrolysis. This pilot study reinforces the
      hypothesis that there is a large interindividual variation in expression of
      carboxylesterases that may contribute to variation in therapeutic outcome and/or
      toxicity of CPT-11 therapy for colon cancer.

PMID- 14581375
TI  - Nucleoside transporter profiles in human pancreatic cancer cells: role of hCNT1
      in 2',2'-difluorodeoxycytidine- induced cytotoxicity.
AB  - PURPOSE: Concentrative nucleoside transporter (CNT) 1, CNT3, equilibrative
      nucleoside transporter (ENT) 1, and, to a lesser extent, ENT2, appear to be the
      transporters responsible for 2',2'-difluorodeoxycytidine (gemcitabine; Gemzar)
      uptake into cells. Gemcitabine is used currently in the treatment of pancreatic
      cancer, but the role of specific nucleoside carrier proteins in gemcitabine
      cytotoxicity has not been elucidated. Indeed, it is not known which nucleoside
      transporters are expressed in human pancreas. EXPERIMENTAL DESIGN: In this study
      we have used four cell lines [pancreatic neoplasia (NP)9, NP18, NP29, and NP31]
      derived from human pancreatic adenocarcinomas to monitor the pattern of
      nucleoside transporter expression, and we have heterologously expressed the high
      affinity gemcitabine transporter human orthologue (h) CNT1 to monitor its role in
      drug responsiveness. RESULTS: All of the cell lines take up gemcitabine mostly
      via the hENT1 transporter, which is expressed at high levels. Reverse
      transcription-PCR analysis of the other four cloned plasma membrane transporter
      mRNAs revealed very different expression patterns among NP cell lines, with
      apparent selective loss or decrease of hCNT mRNAs. NP cells transiently express
      hCNT1-type Na(+)-dependent nucleoside transport activity at low/medium cell
      density but not in confluent cultures. Cells expressing hCNT1 in a more
      constitutive manner were cloned after stable transfection of hCNT1. Despite high
      constitutive hENT1 activity, this increased sensitivity to gemcitabine.
      CONCLUSION: In summary, human pancreatic adenocarcinoma cells overexpress hENT1,
      although they retain the ability to express a functional hCNT1 transporter, an
      isoform that confers sensitivity to gemcitabine.

PMID- 14581376
TI  - Multidrug-resistant tumor cells remain sensitive to a recombinant interleukin-4
      Pseudomonas exotoxin, except when overexpressing the multidrug resistance protein
      MRP1.
AB  - Tumor cells may become resistant to conventional anticancer drugs through the
      occurrence of transmembrane transporter proteins such as P-glycoprotein (ABCB1),
      breast cancer resistance protein (ABCG2), or members of the multidrug resistance
      associated protein family (MRP1-MRP5; ABCC1-ABCC5). In this report, we studied
      whether tumor cells that are cytostatic drug resistant because of overexpression
      of one of the above mentioned proteins are sensitive to a new anticancer agent,
      interleukin-4 toxin (IL-4 toxin). IL-4 toxin is a fusion protein composed of
      circularly permuted IL-4 and a truncated form of Pseudomonas exotoxin (PE) [IL
      4(38-37)-PE38KDEL]. Ninety-six-h cytotoxicity assays and 10-day clonogenic assays
      showed that drug-selected multidrug resistant (MDR) tumor cells that overexpress
      P-glycoprotein or breast cancer resistance proteins are still sensitive to IL-4
      toxin. Also, tumor cells transfected with cDNA for MRP2-5 showed no resistance,
      or marginal resistance, only to the toxin as compared with the parent cells. In
      contrast, MRP1-overexpressing cells, both drug selected and MRP1 transfected, are
      clearly resistant to IL-4 toxin with resistance factors of 4.3 to 8.4. MRP1
      overexpressing cells were not resistant to PE itself. IL-4 toxin resistance in
      MRP1-overexpressing cells could be reversed by the MRP1 inhibitors probenecid or
      MK571 and were not affected by glutathione depletion by DL-buthionine-S,R
      sulfoximine. In a transport assay using plasma membrane vesicles prepared from
      MRP1-overexpressing cells, IL-4 toxin and IL-4, but not PE, inhibited the
      translocation of the known MRP1 substrate 17beta-estradiol 17-(beta-D
      glucuronide) (E(2)17betaG). These data suggest that MRP1-overexpressing cells are
      resistant to IL-4 toxin because of extrusion of this agent by MRP1. Still, the
      results of this study demonstrate that IL-4 toxin effectively kills most MDR
      tumor cells and, therefore, represents a promising anticancer drug.

PMID- 14581377
TI  - Induction of apoptosis by apicidin, a histone deacetylase inhibitor, via the
      activation of mitochondria-dependent caspase cascades in human Bcr-Abl-positive
      leukemia cells.
AB  - PURPOSE: Apicidin, a histone deacetylase inhibitor, is a novel cyclic
      tetrapeptide that exhibits potent antiproliferative activity against various
      cancer cell lines. The aim of this study was to examine the potential of apicidin
      to induce apoptosis in human Bcr-Abl-positive leukemia cells and to assess the
      mechanism of apicidin-induced apoptosis. EXPERIMENTAL DESIGN: Cells were exposed
      to various concentrations of apicidin for 2-72 h, after which the levels of
      apoptosis, histone acetylation, mitochondrial damage, caspase activation, and Bcr
      Abl expression were assessed. RESULTS: Apicidin induced apoptosis in K562 cells
      in a concentration- and time-dependent manner. Similarly, apicidin notably
      induced the apoptosis in the primary leukemic blasts obtained from chronic
      myelogenous leukemia patients in blast crisis. The acetylated histone H4 levels
      increased in a concentration-dependent manner in the K562 cells. However, the
      timing of cell death caused by apicidin did not exactly correlate with the
      histone deacetylase inhibitory effect. The disruption of the mitochondrial
      membrane potential, cytochrome c release into the cytosol, and the mitochondrial
      Bax translocation were notably demonstrated after the apicidin treatment.
      Apicidin induced the proteolytic cleavage of procaspase-9, -3, -8, and poly(ADP
      ribose) polymerase. Pretreatment of the K562 cells with the caspase-3 inhibitor,
      DEVD-CHO, completely inhibited the apicidin-induced apoptosis, suggesting that
      apicidin-induced apoptosis was caspase-dependent. The Fas/Fas ligand death
      receptor pathway was not involved in the apicidin-mediated apoptosis in K562
      cells. Pretreatment of the cells with the caspase-9 inhibitor LEHD-fmk abrogated
      the apicidin- induced cleavage of procaspase-3, -8, and poly(ADP-ribose)
      polymerase. The p210 Bcr-Abl protein levels were notably decreased after the
      apicidin treatment, with near complete loss after 48 h. Reverse transcription-PCR
      assay demonstrated that the Bcr-Abl mRNA level was also remarkably decreased in a
      time-dependent manner. CONCLUSIONS: These results indicate that apicidin
      effectively induces the apoptosis of Bcr-Abl-positive leukemia cells through the
      activation of the mitochondrial pathway-dependent caspase cascades. The down
      regulation of Bcr-Abl mRNA might also be one of the mechanisms implicated in the
      apicidin-mediated apoptosis in the K562 cells. This study provides the rationale
      to additionally investigate apicidin as a potential therapeutic agent for the
      drug-resistant Bcr-Abl-positive leukemia cells.

PMID- 14581378
TI  - Antitumor effects of epidermal growth factor receptor antisense oligonucleotides
      in combination with docetaxel in squamous cell carcinoma of the head and neck.
AB  - PURPOSE: Antisense approaches targeting the epidermal growth factor receptor
      (EGFR) have been demonstrated to inhibit the growth of squamous cell carcinoma of
      the head and neck (SCCHN). Docetaxel is an effective chemotherapeutic agent in
      the treatment of SCCHN. The present study was undertaken to evaluate the
      antitumor mechanisms of EGFR antisense (AS) oligonucleotides administered in
      combination with docetaxel in preclinical models of SCCHN. EXPERIMENTAL DESIGN:
      SCCHN cells lines and xenografts were treated with an EGFR AS oligonucleotide
      targeting region 760-779 of EGFR mRNA (GenBank accession XM_004738) alone and in
      combination with docetaxel. Proliferation in vitro and tumor growth in vivo were
      examined in addition to determinations of EGFR expression and signaling pathways
      to evaluate antitumor mechanisms. RESULTS: A combination of docetaxel with EGFR
      AS resulted in increased cytotoxicity compared with treatment with docetaxel plus
      EGFR sense oligonucleotides or docetaxel alone after 24 h. Tumor volumes were
      significantly reduced in the mice treated with a combination of intratumoral EGFR
      AS and systemic docetaxel compared with mice receiving monotherapy. The
      combination of docetaxel plus EGFR AS resulted in decreased expression levels of
      EGFR, phosphotyrosine signal transducers and activators of transcription 3,
      vascular endothelial growth factor, and pAKT compared with expression levels
      after either treatment alone. CONCLUSIONS: A combination of EGFR AS and docetaxel
      may be effective in the treatment of SCCHN with a reduced toxicity profile
      compared with standard chemotherapy regimens.

PMID- 14581379
TI  - Bryostatin-1 stimulates the transcription of cyclooxygenase-2: evidence for an
      activator protein-1-dependent mechanism.
AB  - Bryostatin-1 (bryostatin) is a macrocyclic lactone derived from Bugula neritina,
      a marine bryozoan. On the basis of the strength of in vitro and animal studies,
      bryostatin is being investigated as a possible treatment for a variety of human
      malignancies. Severe myalgias are a common dose-limiting side effect. Because
      cyclooxygenase-2 (COX-2)-derived prostaglandins can cause pain, we investigated
      whether bryostatin induced COX-2. Bryostatin (1-10 nM) induced COX-2 mRNA, COX-2
      protein, and prostaglandin biosynthesis. These effects were observed in
      macrophages as well as in a series of human cancer cell lines. Transient
      transfections localized the stimulatory effects of bryostatin to the cyclic AMP
      response element of the COX-2 promoter. Electrophoretic mobility shift assays and
      supershift experiments revealed a marked increase in the binding of activator
      protein-1 (AP-1)(c-Jun/c-Fos) to the cyclic AMP response element of the COX-2
      promoter. Pharmacological and transient transfection studies indicated that
      bryostatin stimulated COX-2 transcription via the protein kinase C-->mitogen
      activated protein kinase-->AP-1 pathway. All-trans-retinoic acid, a prototypic AP
      1 antagonist, blocked bryostatin-mediated induction of COX-2. Taken together,
      these results suggest that bryostatin-mediated induction of COX-2 can help to
      explain the myalgias that are commonly associated with treatment. Moreover, it
      will be worthwhile to evaluate whether the addition of a selective COX-2
      inhibitor can increase the antitumor activity of bryostatin.

PMID- 14581380
TI  - Inserting chromosome 18 into pancreatic cancer cells switches them to a dormant
      metastatic phenotype.
AB  - We demonstrated previously that restoration of chromosome 18 suppressed growth of
      pancreatic cancer cells in vitro, as well as that of tumors inoculated into nude
      mice. We also demonstrated that loss of 18q was associated with poor prognosis.
      Hence there is the possibility that the 18q arm harbors a gene(s) implicated in
      tumor progression and/or metastasis. In this study, we evaluated the effect of
      restoring chromosome 18 on metastasis in a few human pancreatic cancer cell lines
      with and without inactivation of SMAD4. After microcell-mediated chromosome 18
      transfer, hybrid cells showed more than a 10-fold weaker metastatic ability than
      corresponding parental cells; mice injected with 1.25 x 10(6)/250 micro l hybrid
      clones via tail vein had less than one-tenth of the number of macroscopic
      metastases in the lung when compared with the control cells. Microscopic
      examination confirmed the decrease in the number of metastatic lesions. After
      inoculation of hybrid cells, more than 80% of the high-power fields showed no
      micrometastases, contrasting with their abundance after using the parental cells.
      Hybrid cells restored maspin expression irrespective of SMAD4 status in
      corresponding parental cells. On the other hand, significantly lower vascular
      endothelial growth factor and matrix metalloproteinase 2 secretion was observed
      by measuring levels in the conditioned media (CM); the averages were 22% and 20%,
      respectively. Angiogenesis assays using in vivo Matrigel plugs demonstrated that
      less neovascularization was observed in nude mice with hybrid cells than with
      corresponding parental cells. When cells were treated with CM from hybrids, the
      migration of human umbilical vascular endothelial cells was decreased, but it was
      partially restored with anti-vascular endothelial growth factor neutralizing
      antibody, as compared with CM from parental cells. These data represent the first
      functional evidence suggesting that chromosome 18q encodes a gene that strongly
      suppresses metastatic activity, possibly through dormancy.

PMID- 14581381
TI  - Oxidative stress and cardiovascular injury: Part II: animal and human studies.

PMID- 14581382
TI  - Biomarkers of vascular disease linking inflammation to endothelial activation:
      Part II.

PMID- 14581383
TI  - Testing endothelial vasomotor function: nitric oxide, a multipotent molecule.

PMID- 14581384
TI  - Endothelial function testing as a biomarker of vascular disease.

PMID- 14581385
TI  - Endothelial dysfunction.

PMID- 14581386
TI  - Images in cardiovascular medicine. Rotational aortogram with three-dimensional
      reconstruction in a case of celiac artery stenosis.

PMID- 14581387
TI  - Kidney disease as a risk factor for development of cardiovascular disease: a
      statement from the American Heart Association Councils on Kidney in
      Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and
      Epidemiology and Prevention.

PMID- 14581388
TI  - Cardiology patient page. Familial dilated cardiomyopathy.

PMID- 14581389
TI  - Images in cardiovascular medicine. Pulmonary venous aneurysms in hereditary
      hemorrhagic telangiectasia detected by 3-dimensional magnetic resonance
      angiography.

PMID- 14581390
TI  - Recurrence of mitral valve regurgitation after mitral valve repair.

PMID- 14581391
TI  - Recurrence of mitral valve regurgitation after mitral valve repair in
      degenerative valve disease.

PMID- 14581392
TI  - Percutaneous closure of patent foramen ovale is the procedure of choice for
      paradoxical embolism.

PMID- 14581393
TI  - Alpha-linolenic acid and nonfatal acute myocardial infarction.

PMID- 14581394
TI  - What are appropriate controls for cardiac interleukin-6 expression in heart
      failure?

PMID- 14581395
TI  - New measurement gives clues to cardiovascular risk.

PMID- 14581396
TI  - Human epicardial adipose tissue is a source of inflammatory mediators.
AB  - BACKGROUND: Inflammatory mediators that originate in vascular and extravascular
      tissues promote coronary lesion formation. Adipose tissue may function as an
      endocrine organ that contributes to an inflammatory burden in patients at risk of
      cardiovascular complications. In this study, we sought to compare expression of
      inflammatory mediators in epicardial and subcutaneous adipose stores in patients
      with critical CAD. METHODS AND RESULTS: Paired samples of epicardial and
      subcutaneous adipose tissues were harvested at the outset of elective CABG
      surgery (n=42; age 65+/-10 years). Local expression of chemokine (monocyte
      chemotactic protein [MCP]-1) and inflammatory cytokines (interleukin [IL]-1beta,
      IL-6, and tumor necrosis factor [TNF]-alpha) was analyzed by TaqMan real-time
      reverse transcription-polymerase chain reaction (mRNA) and by ELISA (protein
      release over 3 hours). Significantly higher levels of IL-1beta, IL-6, MCP-1, and
      TNF-alpha mRNA and protein were observed in epicardial adipose stores.
      Proinflammatory properties of epicardial adipose tissue were noted irrespective
      of clinical variables (diabetes, body mass index, and chronic use of statins or
      ACE inhibitors/angiotensin II receptor blockers) or plasma concentrations of
      circulating biomarkers. In a subset of samples (n=11), global gene expression was
      explored by DNA microarray hybridization and confirmed the presence of a broad
      inflammatory reaction in epicardial adipose tissue in patients with coronary
      artery disease. The above findings were paralleled by the presence of
      inflammatory cell infiltrates in epicardial adipose stores. CONCLUSIONS:
      Epicardial adipose tissue is a source of several inflammatory mediators in high
      risk cardiac patients. Plasma inflammatory biomarkers may not adequately reflect
      local tissue inflammation. Current therapies do not appear to eliminate local
      inflammatory signals in epicardial adipose tissue.

PMID- 14581397
TI  - Interleukin-18 and the risk of coronary heart disease in European men: the
      Prospective Epidemiological Study of Myocardial Infarction (PRIME).
AB  - BACKGROUND: Interleukin (IL)-18 promotes atherosclerotic plaque growth and
      vulnerability. It is unknown, however, whether elevations of circulating IL-18
      precede the onset of coronary events in apparently healthy individuals. METHODS
      AND RESULTS: We evaluated the relationship between baseline plasma levels of IL
      18 and the subsequent incidence of coronary events over a 5-year follow-up in the
      Prospective Epidemiological Study of Myocardial Infarction (PRIME),which included
      10 600 healthy European men aged 50 to 59 years at baseline. Analysis was
      performed in a nested case-control manner comparing 335 cases with a coronary
      event to 670 age-matched controls. Baseline levels of IL-18 were significantly
      higher in men who developed a coronary event than in controls (225.1 versus 203.9
      pg/mL, P=0.005). After adjustment for most potential confounders, including C
      reactive protein, IL-6, and fibrinogen, the relative risk of future coronary
      events associated with increasing tertiles of IL-18 was 1.65 (95% CI 1.14 to
      2.40, P=0.008) in Northern Ireland, 1.29 (95% CI 0.96 to 1.73, P=0.09) in France,
      and 1.42 (95% CI 1.13 to 1.79, P=0.003) in both populations combined (P=0.31 for
      the test of homogeneity between populations). In all models, IL-18 made an
      independent contribution to the prediction of risk over lipids or other
      inflammatory markers such as C-reactive protein, IL-6, or fibrinogen.
      CONCLUSIONS: Plasma IL-18 level was identified as an independent predictor of
      coronary events in healthy, middle-aged European men. Determination of
      circulating IL-18 might improve the prediction of coronary events.

PMID- 14581398
TI  - Crucial role of stromal cell-derived factor-1alpha in neointima formation after
      vascular injury in apolipoprotein E-deficient mice.
AB  - BACKGROUND: Recent evidence indicates that stromal cell-derived factor-1alpha
      (SDF-1alpha) is expressed in human atherosclerotic plaques, whereas high plasma
      levels are clinically associated with stable coronary artery disease. Herein, we
      investigate the involvement of SDF-1alpha in neointimal formation after vascular
      injury. METHODS AND RESULTS: SDF-1alpha was detected by immunohistochemistry in
      carotid arteries of apolipoprotein E-deficient (apoE-/-) mice at various stages
      of neointima formation after wire-induced injury. Double immunofluorescence
      revealed that SDF-1alpha staining was mostly confined to smooth muscle cells
      (SMCs). Furthermore, SDF-1alpha plasma levels peaked 1 day after vascular injury.
      Treatment of apoE-/- mice after carotid injury with a neutralizing SDF-1alpha
      monoclonal antibody for 3 weeks reduced neointimal lesion area by 44% (n=5,
      P<0.05) compared with isotype control. In SDF-1alpha antibody-treated apoE-/-
      mice, neointimal SMC content was decreased (21.7+/-2% versus 39.4+/-4%, n=5,
      P=0.005), whereas the relative content of neointimal macrophages remained
      unchanged. As shown by flow cytometry, carotid injury resulted in a marked
      expansion of circulating Sca-1+lineage- progenitor cells (PBPCs) in the
      peripheral blood of apoE-/- mice after 1 day, which was mediated by SDF-1alpha.
      Systemic injection of isolated PBPCs after vascular injury demonstrated their
      recruitment to neointimal lesions, where they can adopt an SMC-like phenotype.
      CONCLUSIONS: SDF-1alpha plays an instrumental role in neointimal formation after
      vascular injury in apoE-/- mice by regulating neointimal SMC content. This
      contribution appears to be attributable to SDF-1alpha-dependent recruitment of
      circulating SMC progenitor cells.

PMID- 14581399
TI  - Antibodies to oxidized low-density lipoproteins and angiographically assessed
      coronary artery disease in white patients.
AB  - BACKGROUND: Low-density lipoprotein (LDL) can be oxidatively modified by reactive
      oxygen species, thus generating oxLDL. The latter induce formation of specific
      antibodies (oxLDLAb), which are detectable in patients with atherosclerosis, in
      which they might play a pathogenic or a protective role. Thus, we aimed to
      investigate the association of antibodies with oxidized LDLs (oxLDL) (oxLDLAbs)
      with coronary artery disease (CAD) and acute coronary syndromes. METHODS AND
      RESULTS: In a cross-sectional study of 529 consecutive patients undergoing
      quantitative coronary angiography for suspected CAD, we measured the titer of IgG
      oxLDLAbs by ELISA. With regression analysis techniques, we also investigated the
      determinants of oxLDLAb titer and the association of oxLDLAbs with CAD severity.
      We found no significant differences of oxLDLAb titer between groups of patients
      without and with different CAD severity. The oxLDLAb titer was 18.6 enzyme units
      (EU) (11.5 to 25.7 EU/mL) (mean, 95% CI) in patients without CAD; 16.8 EU (9.6 to
      24.2 EU) in patients with stenosis <50%; and 19.9 EU (15 to 24.8 EU), 17.2 (13.8
      to 20.6 EU), and 14.7 EU (12.1 to 17.3 EU) in those with in 1-, 2-, or 3-vessel >
      or =50% stenosis, respectively. Similarly, no differences of oxLDLAb titer
      between patients without and with acute coronary syndrome were found. The oxLDLAb
      titer correlated weakly with aging and with serum total, LDL, and HDL cholesterol
      and plasma homocysteine levels; however, only age and HDL cholesterol remained
      significant predictors of the oxLDLAb titer at a stepwise regression analysis.
      CONCLUSIONS: The results of this study, which was adequately powered from the
      statistical standpoint, provided no evidence for an association of IgG oxLDLAb
      titer with angiographically assessed CAD in whites.

PMID- 14581401
TI  - Feasibility and safety of pulmonary vein isolation using a new mapping and
      navigation system in patients with refractory atrial fibrillation.
AB  - BACKGROUND: Ostial pulmonary vein (PV) isolation by radiofrequency (RF) catheter
      ablation can cure patients with atrial fibrillation (AF); however, this procedure
      carries the risk of PV stenosis. The aim of this study was to assess the
      feasibility of a new mapping and navigation technique using a multipolar basket
      catheter (BC) for PV isolation in patients with refractory AF and to analyze its
      safety with regard to PV stenosis at long-term follow-up. METHODS AND RESULTS: We
      studied 55 patients (mean age, 53+/-11 years; 40 male) with drug-refractory AF
      (paroxysmal, n=37; persistent, n=18). A 64-pole BC was placed transseptally into
      each of the accessible PVs. By use of a nonfluoroscopic navigation system, the
      ablation catheter was guided to the BC electrodes at the PV ostium, with earliest
      activation during sinus rhythm. RF was delivered by use of maximum settings of
      temperature at 50 degrees C and power at 30 W. The end point of the procedure was
      the complete elimination of all distal and fragmented ostial PV potentials. Of
      165 targeted veins, 163 were successfully isolated with a mean RF duration of
      720+/-301 seconds per vein. At 1-year follow-up, 62% of the patients were in
      sinus rhythm without antiarrhythmic drugs. Contrast-enhanced magnetic resonance
      angiography revealed 2 PV stenoses of >25% out of 165 treated vessels.
      CONCLUSIONS: The use of a multipolar BC allowed effective and safe PV isolation
      by combining 3D mapping and navigation. At 1-year follow-up, 62% of the patients
      were in sinus rhythm without antiarrhythmic drugs, and the incidence of relevant
      diameter reduction of the treated PVs was 1.2%.

PMID- 14581400
TI  - Smooth muscle cells in human atherosclerotic plaques express the fractalkine
      receptor CX3CR1 and undergo chemotaxis to the CX3C chemokine fractalkine
      (CX3CL1).
AB  - BACKGROUND: Chemokines are important mediators of inflammatory cell recruitment
      that play a significant role in atherosclerosis. Fractalkine (CX3CL1) is an
      unusual membrane-bound chemokine that mediates chemotaxis through the CX3CR1
      receptor. Recently, functional polymorphisms in the human CX3CR1 gene have been
      described that are associated with coronary artery disease. METHODS AND RESULTS:
      We investigated the expression of the CX3C chemokine fractalkine and its receptor
      CX3CR1 in human coronary artery plaques by immunocytometry. We show that a subset
      of mononuclear cells expresses high levels of fractalkine in human coronary
      atherosclerotic plaques and that smooth muscle cells within the neointima express
      the fractalkine receptor CX3CR1. There is a positive correlation between the
      number of fractalkine-expressing cells and the number of CX3CR1-positive cells in
      human atherosclerotic plaques (r=0.70, n=15 plaques). Furthermore, we demonstrate
      that cultured vascular smooth muscle cells express the CX3CR1 receptor and
      undergo chemotaxis to fractalkine that can be inhibited by G protein inactivation
      by pertussis toxin. CONCLUSIONS: These results suggest that in human
      atherosclerosis, fractalkine, rather than mediating inflammatory cell
      recruitment, can act as a mediator of smooth muscle cell migration.

PMID- 14581402
TI  - Exercise-induced pulmonary edema in heart failure.
AB  - BACKGROUND: In heart failure (HF) patients, exercise may increase pulmonary
      capillary hydrostatic pressure and thereby generate pulmonary edema. If pulmonary
      edema developed, alveolar-capillary membrane conductance (Dm), measured
      immediately after exercise, would decrease. To test this hypothesis, we measured
      Dm before and at 2 and 60 minutes after exercise. METHODS AND RESULTS: We studied
      10 HF patients with exercise-induced periodic breathing, 10 with peak o2 < or =15
      mL x min(-1) x kg(-1) (severe HF), 10 with o2=15 to 20 mL x min(-1) x kg(-1)
      (moderate HF), and 10 normal subjects (control). Using the Roughton-Forster
      technique, we measured carbon monoxide diffusion capacity (DLco) and its
      components, capillary blood volume (Vc) and Dm, at rest and 2 and 60 minutes
      after exercise. At rest, DLco and Dm were lowest in periodic breathing and
      highest in control subjects. Dm decreased in periodic breathing, severe HF, and
      moderate HF (-7.83+/-3.98, -5.57+/-2.03, and -3.85+/-3.53 mL x min(-1) x mm Hg(
      1), respectively; P<0.01) at 2 minutes after exercise but not in control
      subjects. Vc increased in all groups at 2 minutes and remained elevated at 60
      minutes only in periodic breathing. Dm/Vc was decreased in periodic breathing,
      severe HF, and moderate HF at 2 minutes but not in control subjects. Dm and Dm/Vc
      remained low at 60 minutes only in periodic breathing. CONCLUSIONS: Dm decreases
      after exercise in HF patients but not in control subjects, which suggests a
      decrease in conductance across the alveolar-capillary barrier, as with pulmonary
      edema. The reductions were most marked in HF patients with periodic breathing and
      less reduced in less severe HF.

PMID- 14581403
TI  - Comparison of the associations of apolipoprotein B and low-density lipoprotein
      cholesterol with other cardiovascular risk factors in the Insulin Resistance
      Atherosclerosis Study (IRAS).
AB  - BACKGROUND: Risk factors for vascular disease include obesity, dyslipidemia,
      hypertension, dysglycemia, insulin resistance, inflammation, thrombosis, and
      subclinical atherosclerosis. This study compares the associations of
      apolipoprotein B (apoB) and LDL cholesterol (LDLC) with a wide array of measures
      of these risk factors. METHODS AND RESULTS: In 1522 individuals in the Insulin
      Resistance Atherosclerosis Study, anthropometric measures and measures of lipids,
      apoB, C-reactive protein, fibrinogen, plasminogen activator inhibitor-1 (PAI-1),
      fasting and postglucose load glucose and insulin concentrations, and carotid
      artery intima-media thickness (IMT) were taken and insulin sensitivity was
      determined by frequently sampled intravenous glucose tolerance test. There were
      significant differences in measures of abdominal obesity, dyslipidemia,
      hyperinsulinemia, and thrombosis between subjects with elevated apoB but normal
      LDLC versus those with elevated LDLC but normal apoB. In each statistically
      significant comparison, the elevated-apoB group had higher associated risk than
      the elevated-LDLC group. Moreover, apoB is highly significantly (P<0.0001)
      correlated with each measure in the direction of higher risk, whereas LDLC was
      significantly correlated (P<0.05) only with blood pressure, triglyceride,
      fibrinogen, and C-reactive protein. After further adjustment for LDLC, apoB
      correlations remained significant, whereas several LDLC correlations adjusted for
      apoB became significant in the direction of lower risk. CONCLUSIONS: Elevated
      apoB is more strongly associated than LDLC with other risk factors, including
      measures in the National Cholesterol Education Program guidelines for lipid
      treatment and other more recently established risk factors. This may provide new
      insight into why apoB is a better predictor of vascular risk than LDLC.

PMID- 14581404
TI  - Effects of intense and prolonged exercise on insulin sensitivity and glycogen
      metabolism in hypertensive subjects.
AB  - BACKGROUND: The information that insulin sensitivity and glycogen synthesis are
      reduced in hypertension arises primarily from studies using insulin infusions.
      Whether glycogen metabolism is actually altered in a physiological condition,
      such as during and after prolonged exercise, is currently unknown. METHODS AND
      RESULTS: To examine this issue, 9 hypertensive and 11 normotensive subjects were
      evaluated on a rest day and after intense and prolonged exercise on a separate
      day. Insulin sensitivity and hemodynamic variables were measured on both days. On
      the exercise day, whole-body substrate utilization was assessed and muscle
      biopsies were taken in the leg at baseline, immediately after exercise, and 2.5
      and 4 hours after exercise. Insulin sensitivity at rest was lower in hypertensive
      than normotensive subjects (P<0.05) and increased after exercise in normotensive
      (P<0.01) but not in hypertensive (P=NS) subjects. Leg blood flow increased after
      exercise in both groups but to a lesser extent in hypertensive than normotensive
      subjects. Baseline glycogen content and maximal glycogen synthase activity were
      higher in hypertensive than normotensive subjects (P<0.001). Glycogen
      concentration decreased relatively less (-35 versus -66%) and returned to
      baseline levels faster in hypertensive subjects after exercise. Hypertensive
      subjects used approximately 40% less carbohydrates during exercise (P<0.001) at
      the expense of greater free fatty acid oxidation. CONCLUSIONS: It is concluded
      that increased intramuscular glycogen storage and resynthesis in hypertension are
      independent of blood flow and may represent compensatory mechanisms for the
      reduced insulin sensitivity and carbohydrate metabolism in this condition.

PMID- 14581405
TI  - Adverse prognosis of patients with hypertrophic cardiomyopathy who have
      epicardial coronary artery disease.
AB  - BACKGROUND: Adult patients with hypertrophic cardiomyopathy (HCM) may develop
      concomitant atherosclerotic coronary artery disease (CAD). There is a paucity of
      data on the clinical outcomes of HCM patients who have CAD. METHODS AND RESULTS:
      We examined the outcome of 433 adult patients with HCM according to the presence
      and severity of CAD. All patients were aged > or =21 years, had a left
      ventricular ejection fraction of > or =50%, and were without a history of prior
      surgical revascularization (mean age, 63 years; 212 men). Compared with HCM
      patients with mild-to-moderate or no CAD, those with severe CAD demonstrated
      markedly reduced survival. Ten-year overall survival was 46.1%, 70.5%, and 77.1%
      for patients with severe, mild-to-moderate, and no CAD, respectively (unadjusted
      P=0.0001; adjusted P=0.0006). For the end point of cardiac death, this survival
      was 62.3%, 81.0%, and 80.9% (unadjusted P=0.009; adjusted P=0.004). For the end
      point of sudden cardiac death, this survival was 77.4%, 93.2%, and 90.3%
      (unadjusted P=0.01; adjusted P=0.01). The presence of severe CAD also was highly
      predictive of these events (risk ratio for respective event: 2.31, 2.15, and
      2.77) in multivariate models that additionally identified age, prior stroke,
      hyperlipidemia, and atrial fibrillation as significant covariates. CONCLUSIONS:
      Among adult patients with HCM who undergo coronary angiography, those who have
      concomitant severe CAD are at increased risk of death. This risk far exceeds
      historical death rates of CAD patients with normal left ventricular function.

PMID- 14581406
TI  - Characterizing vulnerable plaque features with intravascular elastography.
AB  - BACKGROUND: In vivo detection of vulnerable plaques is presently limited by a
      lack of diagnostic tools. Intravascular ultrasound elastography is a new
      technique based on intravascular ultrasound and has the potential to
      differentiate between different plaques phenotypes. However, the predictive value
      of intravascular elastography to detect vulnerable plaques had not been studied.
      METHODS AND RESULTS: Postmortem coronary arteries were investigated with
      intravascular elastography and subsequently processed for histology. In
      histology, a vulnerable plaque was defined as a plaque consisting of a thin cap
      (<250 microm) with moderate to heavy macrophage infiltration and at least 40% of
      atheroma. In elastography, a vulnerable plaque was defined as a plaque with a
      high strain region at the surface with adjacent low strain regions. In 24
      diseased coronary arteries, we studied 54 cross sections. In histology, 26
      vulnerable plaques and 28 nonvulnerable plaques were found. Receiver operator
      characteristic analysis revealed a maximum predictive power for a strain value
      threshold of 1.26%. The area under the receiver operator characteristic curve was
      0.85. The sensitivity was 88%, and the specificity was 89% to detect vulnerable
      plaques. Linear regression showed high correlation between the strain in caps and
      the amount of macrophages (P<0.006) and an inverse relation between the amount of
      smooth muscle cells and strain (P<0.0001). Plaques, which are declared vulnerable
      in elastography, have a thinner cap than nonvulnerable plaques (P<0.0001).
      CONCLUSIONS: Intravascular elastography has a high sensitivity and specificity to
      detect vulnerable plaques in vitro.

PMID- 14581407
TI  - Aldosterone and not plasminogen activator inhibitor-1 is a critical mediator of
      early angiotensin II/NG-nitro-L-arginine methyl ester-induced myocardial injury.
AB  - BACKGROUND: Angiotensin II (Ang II) increases levels of aldosterone and
      plasminogen activator inhibitor-1 (PAI-1). Both aldosterone and PAI-1 seem to
      promote cardiovascular (CV) injury. Our objective was to determine the roles of
      PAI-1 and aldosterone in the development of myocardial and renal damage in a
      model with high Ang II and low nitric oxide (NO) availability, a pattern seen in
      patients with heart failure, diabetes mellitus, and arteriosclerosis. METHODS AND
      RESULTS: Mice on a moderately high sodium diet were treated with the NO synthase
      inhibitor NG-nitro-l-arginine methyl ester (L-NAME) for 14 days plus Ang II
      during days 8 through 14. The roles of aldosterone and PAI-1 in the development
      of CV injury were assessed using the mineralocorticoid receptor antagonist
      spironolactone (0, 1.5, 15, and 50 mg x 100 g(-1) x day(-1)) and PAI-1-deficient
      mice (PAI-1-/-). Ang II/L-NAME-treated mice showed glomerular ischemia,
      proteinuria, and necrosis of myocytes and vascular smooth muscle cells with an
      associated mixed inflammatory response, deposition of loose collagen, and
      neovascularization. Compared with saline-drinking mice, Ang II/L-NAME-treated
      mice had significantly increased heart to body weight (HW/BW) ratios, cardiac and
      renal damage assessed by histological examination, PAI-1 immunoreactivity, and
      proteinuria. Spironolactone treatment decreased PAI-1 immunoreactivity and
      reduced in a dose-dependent fashion cardiac and renal damage. PAI-1-/- animals
      had a similar degree of CV injury as PAI-1+/+ animals. CONCLUSIONS:
      Mineralocorticoid receptor antagonism, but not PAI-1 deficiency, protected mice
      from developing Ang II/L-NAME-mediated myocardial and vascular injury and
      proteinuria, suggesting that aldosterone, but not PAI-1, plays a key role in the
      development of early Ang II/L-NAME-induced cardiovascular injury.

PMID- 14581408
TI  - Multilineage potential of cells from the artery wall.
AB  - BACKGROUND: In diabetes or atherosclerosis, ectopic bone, fat, cartilage, and
      marrow often develop in arteries. However the mechanism is unknown. We have
      previously identified a subpopulation of vascular cells (calcifying vascular
      cells, CVC), derived by dilutional cloning of bovine aortic medial cells, and
      showed that they undergo osteoblastic differentiation and mineralization. We now
      show that CVC have the potential to differentiate along other mesenchymal
      lineages. METHODS AND RESULTS: To determine the multilineage potential of CVC,
      molecular and functional markers of multiple mesenchymal lineages were assessed.
      Chondrogenic potential of CVC was evidenced by expression of types II and IX
      collagen and cytochemical staining for Alcian blue. Leiomyogenic potential of CVC
      was evidenced by the expression of smooth muscle-alpha actin, calponin,
      caldesmon, and myosin heavy chain. Stromogenic potential of CVC was evidenced by
      the ability to support growth of colony-forming units of hematopoietic progenitor
      cells from human CD34+ umbilical cord blood cells for a period of 5 weeks.
      Adipogenic potential was not observed. CVC were immunopositive to antigens to
      CD29 and CD44 but not to CD14 or CD45, consistent with other mesenchymal stem
      cells. CVC retained multipotentiality despite passaging and expansion through
      more than 20 to 25 population triplings, indicating a capacity for self-renewal.
      CONCLUSIONS: These results suggest that the artery wall contains cells that have
      the potential for multiple lineages similar to mesenchymal stem cells but with a
      unique differentiation repertoire.

PMID- 14581409
TI  - Reinduction of T-type calcium channels by endothelin-1 in failing hearts in vivo
      and in adult rat ventricular myocytes in vitro.
AB  - BACKGROUND: In ventricular myocardium, the T-type Ca2+ current (ICa,T), which is
      temporarily observed during fetal and neonatal periods, has been shown to
      reappear in failing/remodeling hearts. However, its pathophysiological regulation
      has not been elucidated. METHODS AND RESULTS: We utilized Dahl salt-sensitive
      (DS) rats with hypertension at the stage of concentric left ventricular (LV)
      hypertrophy (11 weeks old, LVH) and at the heart failure stage (16 to 18 weeks
      old, CHF). Some were treated with bosentan (100 mg/kg per day) during the period
      from LVH to CHF. In LVH, neither the presence of ICa,T (measured in the freshly
      isolated LV myocytes) nor an increase in alpha-1G mRNA expression were detected.
      This condition was associated with increases in tissue angiotensin II (AII) but
      not with endothelin (ET)-1 peptides. In contrast, in CHF, when the tissue AII
      remained elevated and ET-1 de novo increased, ICa,T was recorded in most of the
      cells (-0.87+/-0.18 pA/pF at -30 mV, P<0.01 versus LVH). This was associated with
      a significant increase in the alpha-1G mRNA level. The chronic bosentan treatment
      eliminated both the elevation of alpha-1G mRNA level and ICa,T from the cells,
      whereas it did not affect the cell size and membrane capacitance. In addition, 48
      hour exposure to ET-1 but not AII induced ICa,T in normal adult myocytes in
      culture from Sprague-Dawley rats. CONCLUSIONS: ICa,T channels reappear in failing
      but not in hypertrophied LV cardiomyocytes in a manner depending on the tissue ET
      1 activation.

PMID- 14581410
TI  - Relevance of monocytic features for neovascularization capacity of circulating
      endothelial progenitor cells.
AB  - BACKGROUND: Transplantation of ex vivo expanded circulating endothelial
      progenitor cells (EPCs) from peripheral blood mononuclear cells improves the
      neovascularization after critical ischemia. However, the origin of the
      endothelial progenitor lineage and its characteristics have not yet been clearly
      defined. Therefore, we investigated whether the phenotype and functional capacity
      of EPCs to improve neovascularization depend on their monocytic origin. METHODS
      AND RESULTS: Monocytic CD14+ cells were isolated from mononuclear cells and
      incubated on fibronectin-coated dishes in endothelial medium in the presence of
      vascular endothelial growth factor. After 4 days of cultivation, adherent cells
      deriving from CD14+ or CD14- mononuclear cells showed equal expression of
      endothelial marker proteins and capacity for clonal expansion as determined by
      measuring endothelial colony-forming units. In addition, transplanted EPCs
      (5x10(5) cells) deriving from CD14+ or CD14- cells were incorporated into
      vascular structures of nude mice after hind-limb ischemia and significantly
      improved neovascularization from 0.27+/-0.12 (no cells) to 0.66+/-0.12 and 0.65+/
      0.17, respectively (P<0.001; laser Doppler-derived relative blood flow). In
      contrast, no functional improvement of neovascularization was detected when
      freshly isolated CD14+ mononuclear cells without ex vivo expansion were used
      (0.33+/-0.17). Moreover, macrophages or dendritic cells differentiated from
      isolated CD14+ cells were significantly less effective in improving
      neovascularization than EPCs cultivated from the same starting population
      (P<0.01). CONCLUSIONS: These data demonstrate that EPCs can be generated from
      nonmonocytic CD14- peripheral blood mononuclear cells and exhibit a unique
      functional activity to improve neovascularization after hind-limb ischemia.

PMID- 14581411
TI  - Epiregulin as a major autocrine/paracrine factor released from ERK- and p38MAPK
      activated vascular smooth muscle cells.
AB  - BACKGROUND: The coordinated activation of extracellular signal-regulated kinase
      (ERK) and p38 mitogen-activated protein kinase (p38MAPK) is critical for the
      induction of vascular and visceral smooth muscle cell (SMC) dedifferentiation. We
      previously reported that on the forced activation of both MAPKs, visceral SMCs
      secrete a non-heparin-binding protein factor(s) that is involved in the
      dedifferentiation of neighboring SMCs. In this study, we sought to identify the
      dedifferentiation factor(s) derived from vascular SMCs (VSMCs). METHODS AND
      RESULTS: We fractionated the VSMC dedifferentiation factor(s) in the conditioned
      medium obtained from differentiated VSMCs in which both ERK and p38MAPK were
      forcedly activated and identified epiregulin as a major autocrine/paracrine
      factor for VSMC dedifferentiation. The epiregulin-induced VSMC dedifferentiation
      was mediated through the coordinated activation of ERK and p38MAPK. Unsaturated
      lysophosphatidic acid and platelet-derived growth factor-BB, which are potent
      VSMC dedifferentiation factors, rapidly upregulated epiregulin mRNA expression in
      an ERK- and p38MAPK-dependent manner. Reverse transcriptase-polymerase chain
      reaction and/or immunohistological analyses revealed the restricted expression of
      epiregulin in human atherosclerotic and balloon-injured rat arteries, in which
      the phenotypic modulation of medial VSMCs occurred in vivo. CONCLUSIONS:
      Epiregulin is released from VSMCs primed by atherogenic factors and acts as a
      major autocrine/paracrine factor for VSMC dedifferentiation. It may be involved
      in the progression of vascular remodeling such as atherosclerosis.

PMID- 14581412
TI  - Hysteresis effect implicates calcium cycling as a mechanism of repolarization
      alternans.
AB  - BACKGROUND: T-wave alternans is due to alternation of membrane repolarization at
      the cellular level and is a risk factor for sudden cardiac death. Recently, a
      hysteresis effect has been reported in patients whereby T-wave alternans, once
      induced by rapid heart rate, persists even when heart rate is subsequently
      slowed. We hypothesized that alternans hysteresis is an intrinsic property of
      cardiac myocytes, directly related to an underlying mechanism for repolarization
      alternans that involves intracellular calcium cycling. METHODS AND RESULTS:
      Stepwise pacing was used to induce alternans in Langendorff-perfused guinea pig
      hearts from which optical action potentials were recorded simultaneously at 256
      ventricular sites with voltage-sensitive dyes and in whole-cell patch-clamped
      cardiac myocytes treated with or without BAPTA-AM (1,2-bis[2-aminophenoxy]ethane
      N,N,N',N'-tetraacetic acid tetrakis [acetoxymethyl ester]). Alternans hysteresis
      was observed in every isolated heart: threshold heart rate for alternans was
      280+/-12 bpm, but during subsequent deceleration of pacing, alternans persisted
      to significantly slower heart rates (238+/-5 bpm, P<0.05). Optical mapping showed
      that this effect also applied to the threshold for spatially discordant alternans
      (313+/-2.2 bpm during acceleration versus 250+/-6.6 bpm during deceleration,
      P<0.05). Alternans hysteresis was also observed in isolated cardiac myocytes.
      Moreover, calcium chelation by BAPTA-AM raised the threshold for alternans and
      inhibited hysteresis in a dose-dependent manner with no effect on baseline action
      potential duration. CONCLUSIONS: Alternans hysteresis is an intrinsic property of
      cardiac myocytes that can lead to persistence of arrhythmogenic discordant
      alternans even after heart rate is slowed. These results also support an
      important underlying role of calcium cycling in the mechanism of alternans.

PMID- 14581413
TI  - Inactivation of macrophage scavenger receptor class B type I promotes
      atherosclerotic lesion development in apolipoprotein E-deficient mice.
AB  - BACKGROUND: Scavenger receptor class B type I (SR-BI) is expressed in
      macrophages, where it has been proposed to facilitate cholesterol efflux.
      However, direct evidence that the expression of macrophage SR-BI is protective
      against atherosclerosis is lacking. In this study, we examined the in vivo role
      of macrophage SR-BI in atherosclerotic lesion development in the apolipoprotein
      (apo) E-deficient mouse model. METHODS AND RESULTS: ApoE-deficient mice with
      (n=16) or without (n=15) expression of macrophage SR-BI were created by
      transplanting lethally irradiated apoE-deficient mice with bone marrow cells
      collected from SR-BI-/- apoE-/- mice or SR-BI+/+ apoE-/- mice. The recipient mice
      were fed a chow diet for 12 weeks after transplantation for analysis of
      atherosclerosis. Quantification of macrophage SR-BI mRNA by real-time reverse
      transcription-polymerase chain reaction indicated successful engraftment of donor
      bone marrow and inactivation of macrophage SR-BI in recipient mice reconstituted
      with SR-BI-/- apoE-/- bone marrow. There were no significant differences in
      plasma lipid levels, lipoprotein distributions, and HDL subpopulations between
      the 2 groups. Analysis of the proximal aorta demonstrated an 86% increase in mean
      atherosclerotic lesion area in SR-BI-/- apoE-/- --> apoE-/- mice compared with SR
      BI+/+ apoE-/- --> apoE-/- mice (109.50+/-18.08 versus 58.75+/-9.58x10(3) microm2;
      mean+/-SEM, P=0.017). No difference in cholesterol efflux from SR-BI+/+ apoE-/-
      or SR-BI-/- apoE-/- macrophages to HDL or apoA-I discs was detected. CONCLUSIONS:
      Expression of macrophage SR-BI protects mice against atherosclerotic lesion
      development in apoE-deficient mice in vivo without influencing plasma lipids, HDL
      subpopulations, or cholesterol efflux. Thus, macrophage SR-BI plays an
      antiatherogenic role in vivo, providing a new therapeutic target for the design
      of strategies to prevent and treat atherosclerosis.

PMID- 14581414
TI  - Reduction of infarct size and prevention of cardiac rupture in transgenic mice
      overexpressing FrzA.
AB  - BACKGROUND: FrzA/sFRP-1, a secreted, frizzled-related protein and antagonist for
      the wnt/frizzled pathway, is expressed in the heart and vessels during mouse
      embryogenesis and adulthood. FrzA is involved in cell cycle control of vascular
      cells and angiogenesis. We assessed the hypothesis that FrzA could control the
      healing process after myocardial infarction (MI). METHODS AND RESULTS: We
      demonstrated an upregulation of sFRP-1 and distinct wnt and fz member expression
      after MI. We established transgenic (Tg) mice that overexpress FrzA under a
      cytomegalovirus promoter and developed a model of MI by coronary artery ligation.
      FrzA reduced cardiac rupture after MI in Tg (6.5% versus 26.4% in controls;
      n=165, P<0.01). MI was smaller in Tg at each time point (18+/-10.8% of left
      ventricular circumference versus 30+/-14.2% in controls at day 30; P<0.001).
      Similar results were found in cryolesion-induced MI. Cardiac function was
      improved in Tg mice (3800+/-370 mm Hg/s dP/dtmax versus 2800+/-840 in controls; 
      2800+/-440 dP/dtmin versus -1800+/-211 in controls at day 15; P<0.001). Early
      leukocyte infiltration had decreased in Tg mice during the first week. Apoptotic
      index was decreased by 50% in Tg mice at day 7. Matrix metalloproteinase-2 and -9
      activity was reduced in Tg mice at day 4, and collagen deposition in the scar was
      increased in Tg mice. Capillary density in the scar was higher in Tg mice (290+/
      103 vessels/mm2 versus 104+/-43 in controls at day 15; P<0.001). Vessels were
      more muscularized, and mean lumen area was 3-fold higher in Tg animals.
      CONCLUSIONS: Overexpression of FrzA, through direct or indirect interaction with
      different phases of infarct healing, reduced infarct size and improved cardiac
      function.

PMID- 14581416
TI  - Binet's staging system and VH genes are independent but complementary prognostic
      indicators in chronic lymphocytic leukemia.
AB  - PURPOSE: Rai's and Binet's staging systems have contributed significantly to the
      identification of major prognostic groups in chronic lymphocytic leukemia (CLL),
      though they fail to accurately predict disease progression at the individual
      level. Biologic factors, such as the mutational status of the immunoglobulin
      heavy-chain variable genes (VH, cytogenetics, CD38 expression, and some serum
      markers, have recently improved prognostic assessment in CLL. In this study, we
      analyzed the prognostic value of VH mutational status within the different stages
      of Binet's classification in 145 patients. PATIENTS AND METHODS: Our series
      consisted of 83 VH mutated (MT) and 62 VH unmutated (UM) patients. MT cases
      predominated within Binet's stage A (70%), whereas UM cases predominated among
      stages B and C (62%). RESULTS: Median overall survival (OS) was 84 months for UM
      patients and was not achieved for the MT group (70% 12-year survival, P <.0001).
      Concerning Binet's stage A, both median OS and progression-free survival were
      significantly shorter for UM patients when compared with those of MT patients (97
      months v not achieved, P =.0017; and 42 v 156 months, P <.0001), which compared
      favorably with the classical A' and A" substaging. The VH mutational profile
      could also segregate stage B and C patients into two groups with different
      survival patterns (median OS, 78 v 120 months for UM and MT patients,
      respectively; P =.002). CONCLUSION: The significant survival differences observed
      between the VH mutational groups, among stage A and stage B and C patients,
      indicate that Binet's classification and VH genes are independent prognostic
      variables and are most likely complementary.

PMID- 14581415
TI  - Three-arm randomized study of two cisplatin-based regimens and paclitaxel plus
      gemcitabine in advanced non-small-cell lung cancer: a phase III trial of the
      European Organization for Research and Treatment of Cancer Lung Cancer Group-
      EORTC 08975.
AB  - PURPOSE: To compare the therapeutic efficacy of paclitaxel plus cisplatin (arm A)
      versus gemcitabine plus cisplatin (arm B) and arm A versus paclitaxel plus
      gemcitabine (arm C) in chemotherapy-naive patients with advanced non-small-cell
      lung cancer (NSCLC). MATERIALS AND METHODS: Patients were randomly assigned to
      receive either paclitaxel 175 mg/m2 (3-hour infusion, day 1) or gemcitabine 1,250
      mg/m2 (days 1 and 8) both combined with cisplatin 80 mg/m2 (day 1) or paclitaxel
      175 mg/m2 (3-hour infusion, day 1) combined with gemcitabine 1,250 mg/m2 (days 1
      and 8). Primary end point was comparison of overall survival for B versus A and C
      versus A. Secondary end points included response rate and duration, progression
      free survival, toxicities, quality of life [QoL], and cost of treatment. RESULTS:
      Four hundred eighty patients (arm A, 159; arm B, 160; arm C, 161 patients) were
      enrolled; all baseline characteristics were balanced. Median survival times were
      as follows: arm A, 8.1 months; arm B, 8.9 months; arm C, 6.7 months. Response
      rates were 31.8% for arm A, 36.6% for arm B, and 27.7% for arm C. Other than
      myelosuppression (B v A, P <.005), no statistically or clinically significant
      differences were observed for secondary end points. The average treatment costs
      were 25% higher in arm C as compared with arms A and B. CONCLUSION: Gemcitabine
      plus cisplatin and paclitaxel plus gemcitabine do not increase overall survival
      in patients with advanced NSCLC as compared with paclitaxel plus cisplatin.
      Treatment was well tolerated, and most QoL parameters were similar, but costs
      associated with the nonplatinum arm were highest.

PMID- 14581417
TI  - Assessment of differences in patient populations selected for excluded from
      participation in clinical phase III acute myelogenous leukemia trials.
AB  - PURPOSE: To compare patients treated in or outside clinical protocols, using de
      novo acute myeloid leukemia (AML) as a model disorder. PATIENTS AND METHODS: We
      retrospectively compared the characteristics of all patients with de novo AML
      diagnosed in the referral area of our university hospital between 1985 and 1994.
      RESULTS: Of a total of 170 AML patients, 45% were included in a phase III trial
      for the treatment of AML and 55% were treated outside a protocol. Another 45
      patients were registered only at diagnosis but were treated elsewhere. Nonstudy
      patients differed significantly from patients included in clinical trials with
      respect to age and performance status at clinical presentation, comorbidity, and
      type of AML. The great majority of patients excluded from trial participation
      showed distinct exclusion criteria, such as advanced age and severe comorbidity.
      Study patients were treated significantly more often with curative intent and
      achieved better response and survival. Patients treated in an equivalent manner
      but outside a protocol showed no significant difference in survival compared with
      patients enrolled onto a trial. CONCLUSION: Study patients were not
      representative for the entire population of patients with AML; many patients were
      excluded from phase III trial participation for failure to meet stringent entry
      criteria. Therefore, results of phase III studies may not be extrapolated to all
      AML patients but should only be applied to patients who do not differ in
      substantial characteristics from the study population.

PMID- 14581418
TI  - Clinical features and outcome of primary effusion lymphoma in HIV-infected
      patients: a single-institution study.
AB  - PURPOSE: To describe the clinical features and outcome of HIV-associated primary
      effusion lymphoma (PEL) and to compare them with those of the other HIV
      associated non-Hodgkin's lymphomas (NHLs). PATIENTS AND METHODS: From April 1987
      to June 2002, 277 patients with HIV infection and systemic NHL were diagnosed and
      treated in our institution. Clinical features and outcome of PEL patients were
      compared with the features and outcomes of 162 patients belonging to the
      following histologic subtypes: plasmoblastic lymphoma of oral cavity (PBLOC, n =
      11), immunoblastic lymphoma (IBL, n = 76), and centroblastic B-cell lymphoma
      (CBCL, n = 75). RESULTS: Among the 277 NHL patients, PEL was diagnosed in 11
      patients (4%). Eight of 11 patients were treated with a cyclophosphamide,
      doxorubicin, vincristine, and prednisone (CHOP)-like regimen. Complete remission
      was reached in 42% of patients, with a median survival time of 6 months. When the
      clinical features and outcome of 11 PEL patients were compared with the other
      three groups of patients affected by NHL, at the onset of the disease, no
      statistically significant differences were observed in demographic data, CD4
      absolute number, HIV viremia plasma levels, and clinical characteristics. When we
      compared the outcome of PEL patients with the CBCL group, a statistically
      significant worse outcome was observed; however, the clinical outcome of PEL
      patients was not significantly different from the outcome observed in the other
      two groups (PBLOC and IBL groups). CONCLUSION: PEL is a rare HIV-associated NHL
      type occurring as a late manifestation of HIV infection with a poor clinical
      outcome and a shorter overall survival compared with CBCL patients.

PMID- 14581419
TI  - Phase III trial of long-term adjuvant androgen deprivation after neoadjuvant
      hormonal cytoreduction and radiotherapy in locally advanced carcinoma of the
      prostate: the Radiation Therapy Oncology Group Protocol 92-02.
AB  - PURPOSE: Radiation Therapy Oncology Group (RTOG) Protocol 92-02 was a randomized
      trial testing long-term (LT) adjuvant androgen deprivation (AD) after initial AD
      with external-beam radiotherapy (RT) in patients with locally advanced prostate
      cancer (PC; T2c-4) and with prostate-specific antigen level less than 150 ng/mL.
      PATIENTS AND METHODS: Patients received a total of 4 months of goserelin and
      flutamide, 2 months before and 2 months during RT. A radiation dose of 65 to 70
      Gy was given to the prostate and a dose of 44 to 50 Gy to the pelvic lymph nodes.
      Patients were randomly assigned to receive no additional therapy (short-term
      [ST]AD-RT) or 24 months of goserelin (LTAD-RT); 1,554 patients were entered onto
      the study. RESULTS: The LTAD-RT arm showed significant improvement in all
      efficacy end points except overall survival (OS; 80.0% v 78.5% at 5 years, P
      =.73), compared with the STAD-RT arm. In a subset of patients not part of the
      original study design, with tumors assigned Gleason scores of 8 to 10 by the
      contributing institutions, the LTAD-RT arm had significantly better OS (81.0% v
      70.7%, P =.044). There was a small but significant increase in the frequency of
      late radiation grades 3, 4, and 5 gastrointestinal toxicity ascribed to the LTAD
      RT arm (2.6% v 1.2% at 5 years, P =.037), the cause of which is not clear.
      CONCLUSION: The RTOG 92-02 trial supports the addition of LT adjuvant AD to STAD
      with RT for T2c-4 PC. In the exploratory subset analysis of patients with Gleason
      scores 8 to 10, LT adjuvant AD resulted in a survival advantage.

PMID- 14581420
TI  - Time course and predictors of symptoms after primary prostate cancer therapy.
AB  - PURPOSE: Understanding the distinctive patterns of treatment-related dysfunction
      after alternative initial treatments for early prostate cancer (PC) may improve
      patients' choice of treatment and later help them adjust to its consequences. We
      characterized the time course of treatment complications while adjusting for
      potentially confounding pretreatment factors hindering other observational
      studies. PATIENTS AND METHODS: In a prospective cohort study of 417 men we
      assessed urinary, bowel, and sexual function from before primary treatment to 24
      months after. To control for potential confounding, we measured sociodemographic
      and PC prognostic factors, medical comorbidity, and pretreatment function
      commonly affected by PC and its treatment. RESULTS: Patients who underwent
      external beam radiotherapy (EBRT), radical prostatectomy (RP), and brachytherapy
      (BT) differed significantly in sociodemographic factors, cancer prognostic
      factors, and pretreatment symptom status, especially sexual function. Urinary
      incontinence increased sharply after RP, while bowel problems and urinary
      irritation/obstruction rose after EBRT and BT. Sexual dysfunction increased in
      all patients, particularly after radical prostatectomy, and nerve-sparing
      surgical technique had little apparent benefit. There was no change in urinary
      function and little change in overall bowel function after 12 months, but the
      time course of sexual dysfunction varied by treatment and, for bowel function, by
      symptom. Multiple regression modeling confirmed that treatment influences all 24
      month outcomes, but residual confounding persisted. CONCLUSION: Pretreatment
      function and the primary treatment modality for early stage PC strongly predict
      the affected organ systems and time course of dysfunction. With this information,
      patients and their physicians may refine their choice of treatment and better
      anticipate its consequences.

PMID- 14581421
TI  - Subcutaneous interleukin-2 and interferon alfa administration in patients with
      metastatic renal cell carcinoma: final results of SCAPP III, a large,
      multicenter, phase II, nonrandomized study with sequential analysis design--the
      Subcutaneous Administration Propeukin Program Cooperative Group.
AB  - PURPOSE: This outpatient multicenter trial tested the hypothesis that
      subcutaneous administration of an interleukin-2 (IL-2)/interferon alfa (IFN
      alpha) combination produces a response rate greater than 20% in patients with
      renal cell carcinoma (RCC). PATIENTS AND METHODS: Patients with metastatic RCC
      received a 12-week induction treatment with subcutaneous IL-2 (5 days/wk, 9 and
      18 million U/d)/IFN alpha (3 days/wk, 6 million U/d). After evaluation, patients
      with objective response or stable disease were randomly assigned to maintenance
      treatment or short consolidation treatment. RESULTS: Lack of benefit was shown at
      the 12th sequential analysis, and the trial was closed. At the end of the
      induction period, 26 (21%) of 122 patients had objective responses (including six
      complete responses). Thirty-three patients (27%) developed severe toxicity
      requiring dose reductions, delayed treatment, or treatment termination. Survival
      rates at one, two, and four years were 63%, 38%, and 17%, respectively. Three
      year survival was 20% in patients with two poor prognosis factors and 37% in
      patients with one or no poor prognosis factors (P =.016). Three-year survival was
      significantly better (P < 10-3) in patients with erythrocyte sedimentation rate
      less than 35 mm (43%) compared with those with 1-hour sedimentation rate greater
      than 35 mm (19%). CONCLUSION: This study confirms the importance of prognostic
      factors when initiating cytokine immunotherapy in patients with metastatic RCC
      and underlines the prognostic value of erythrocyte sedimentation rate before
      treatment initiation. Nonetheless, this subcutaneous IL-2/IFN alpha combination
      does not improve response rate or survival compared with subcutaneous IL-2 alone,
      although a definitive conclusion cannot be drawn in the absence of a randomized
      study comparing the two treatments.

PMID- 14581422
TI  - F-18 fluorodeoxyglucose positron emission tomography in the evaluation of distant
      metastases from renal cell carcinoma.
AB  - PURPOSE: We conducted a study to evaluate the role of F-18 fluorodeoxyglucose
      (FDG) positron emission tomography (PET) in the detection of distant metastases
      from renal cell carcinoma (RCC). MATERIALS AND METHODS: Twenty-four patients with
      histologically proven clear-cell RCC undergoing surgical evaluation for possible
      resection of recurrent disease were investigated. All patients had suspected
      distant metastases based on conventional anatomic imaging techniques (computed
      tomography and magnetic resonance imaging). A total of 36 distant metastatic
      sites were identified. Pathology for all sites was obtained by biopsy or after
      surgical resection. RESULTS: Histologically documented distant metastases from
      RCC were present in 33 sites (21 patients). Overall sensitivity, specificity, and
      positive predictive value of FDG-PET for the detection of distant metastases from
      RCC was 63.6% (21 of 33), 100% (three of three), and 100% (21 of 21),
      respectively. The mean size of distant metastases in patients with true-positive
      FDG-PET was 2.2 cm (95% CI, 1.7 to 2.6 cm) compared with 1.0 cm in patients with
      false-negative FDG-PET (95% CI, 0.7 to 1.4 cm; P =.001). CONCLUSION: FDG-PET is
      not a sensitive imaging modality for the evaluation of metastatic RCC and may not
      adequately characterize small metastatic lesions. However, positive FDG-PET is
      predictive for the presence of RCC in lesions imaged, may complement anatomic
      radiologic imaging modalities, and may alleviate the need for a biopsy in
      selected situations. A negative FDG-PET, however does not rule out active
      malignancy.

PMID- 14581423
TI  - Temporarily deferred therapy (watchful waiting) for men younger than 70 years and
      with low-risk localized prostate cancer in the prostate-specific antigen era.
AB  - PURPOSE: Watchful waiting (WW) is an acceptable strategy for managing prostate
      cancer (PC) in older men. Prostate-specific antigen (PSA) testing has resulted in
      a stage migration, with diagnoses made in younger men. An analysis of the
      Department of Defense Center for Prostate Disease Research Database was
      undertaken to document younger men with low- or intermediate-grade PC who
      initially chose WW. PATIENTS AND METHODS: We identified men choosing WW who were
      diagnosed between January 1991 and January 2002, were 70 years or younger, had a
      Gleason score < or = 6 with no Gleason pattern 4, had no more than three positive
      cores on biopsy, and whose clinical stage was < or = T2 and PSA level was < or =
      20. We analyzed their likelihood of remaining on WW, the factors associated with
      secondary treatment, and the influence of comorbidities. RESULTS: Three hundred
      thirteen men were identified. Median follow-up time was 3.8 years. Median age was
      65.4 years (range, 41 to 70 years). Ninety-eight patients remained on WW; 215
      proceeded to treatment. A total of 57.3% and 73.2% chose treatment within the
      first 2 and 4 years, respectively. Median PSA doubling time (DT) was 2.5 years
      for those who underwent therapy; those remaining on WW had a median DT of 25.8
      years. The type of secondary treatment was associated with the number of
      patient's comorbidities (P =.012). CONCLUSION: Younger patients who choose WW
      seemed more likely to receive secondary treatment than older patients. PSA DTs
      often predict the use of secondary treatment. The number of comorbidities a
      patient has influences the type of secondary therapy chosen. The WW strategy may
      better be termed temporarily deferred therapy.

PMID- 14581424
TI  - Preoperative mitomycin, ifosfamide, and cisplatin followed by esophagectomy in
      squamous cell carcinoma of the esophagus: pathologic complete response induced by
      chemotherapy leads to long-term survival.
AB  - PURPOSE: Squamous cell carcinoma of the esophagus remains an aggressive disease
      with a poor prognosis, even after curative-intent surgery. This article analyzes
      the impact of preoperative chemotherapy with mitomycin, ifosfamide, and cisplatin
      (MIC) on a cohort of 68 patients. PATIENTS AND METHODS: From 1988 to 1994, 68
      patients with potentially operable squamous cell carcinoma of the esophagus were
      entered onto two phase II trials of neoadjuvant chemotherapy with mitomycin 6
      mg/m2, ifosfamide 3 g/m2, and cisplatin 50 mg/m2 and received between two and
      four cycles of treatment at 3-weekly intervals. Two patients were removed from
      the analysis when they were found to have malignancy other than squamous cell
      carcinoma of the esophagus. RESULTS: Forty (61%) of 66 patients had a radiologic
      response to chemotherapy (18 complete responses and 22 partial responses), and 52
      (79%) of 66 patients went on to have the primary tumor resected. There were nine
      pathologic complete responders, seven of whom remain fit and well after at least
      60 months of follow-up. The overall median survival was 12.4 months (95%
      confidence interval, 9.6 to 18.8 months). The complete response and node-negative
      patients survived significantly longer than those in other categories (log-rank
      chi2 = 18.8; P <.001): on average 13 months longer than the node-positive or
      nonresected category (22.0 v 9.4 months). The toxicity of the regimen was low.
      CONCLUSION: MIC is an easily administered, well-tolerated, and efficacious
      regimen as neoadjuvant therapy for patients with squamous cell carcinoma of the
      esophagus. These results warrant further investigation.

PMID- 14581426
TI  - Breast cancer in older women: quality of life and psychosocial adjustment in the
      15 months after diagnosis.
AB  - PURPOSE: We examined the health-related quality of life (QOL) of a cohort of
      older women with breast cancer after their diagnosis. PATIENTS AND METHODS: Six
      hundred ninety-one women aged 65 years and older were interviewed approximately 3
      months after breast cancer surgery and two additional times in the following year
      using standardized QOL measures. Demographic factors, breast cancer treatments,
      and comorbid conditions were used to model ratings of health-related QOL over
      time. Self-perceived health and psychosocial adjustment at 15 months after
      surgery were modeled. RESULTS: Physical and mental health scores declined
      significantly in the follow-up year, independent of age. However, a cancer
      specific psychosocial instrument showed significant improvement in scores. Better
      3-month physical and mental health scores, as well as better emotional social
      support, predicted more favorable self-perceived health 15 months after surgery.
      Psychosocial adjustment at 15 months was significantly predicted by better mental
      health, emotional social support, and better self-rated interaction with health
      care providers assessed at 3 months. CONCLUSION: Contrary to reports from younger
      women with breast cancer, we observed significant declines in the physical and
      mental health of older women in the 15 months after breast cancer surgery,
      whereas scores on a cancer-specific psychosocial QOL measure improved over time,
      consistent with patterns in younger women. Predictive models indicate that older
      women with impaired physical functioning, mental health, and emotional social
      support after surgery have poorer self-perceived health and psychosocial
      adjustment 1 year later. Interventions to address the physical and emotional
      needs of older women with breast cancer should be developed and evaluated to
      determine their impact on subsequent health-related QOL.

PMID- 14581425
TI  - Clinical and immunologic results of a randomized phase II trial of vaccination
      using four melanoma peptides either administered in granulocyte-macrophage colony
      stimulating factor in adjuvant or pulsed on dendritic cells.
AB  - PURPOSE: To determine clinical and immunologic responses to a multipeptide
      melanoma vaccine regimen, a randomized phase II trial was performed. PATIENTS AND
      METHODS: Twenty-six patients with advanced melanoma were randomly assigned to
      vaccination with a mixture of four gp100 and tyrosinase peptides restricted by
      HLA-A1, HLA-A2, and HLA-A3, plus a tetanus helper peptide, either in an emulsion
      with granulocyte-macrophage colony-stimulating factor (GM-CSF) and Montanide ISA
      51 adjuvant (Seppic Inc, Fairfield, NJ), or pulsed on monocyte-derived dendritic
      cells (DCs). Systemic low-dose interleukin-2 (Chiron, Emeryville, CA) was given
      to both groups. T-lymphocyte responses were assessed, by interferon gamma ELIspot
      assay (Chiron, Emeryville, CA), in peripheral-blood lymphocytes (PBLs) and in a
      lymph node draining a vaccine site (sentinel immunized node [SIN]). RESULTS: In
      patients vaccinated with GM-CSF in adjuvant, T-cell responses to melanoma
      peptides were observed in 42% of PBLs and 80% of SINs, but in patients vaccinated
      with DCs, they were observed in only 11% and 13%, respectively. The overall
      immune response was greater in the GM-CSF arm (P <.02). Vitiligo developed in two
      of 13 patients in the GM-CSF arm but in no patients in the DC arm. Helper T-cell
      responses to the tetanus peptide were detected in PBLs after vaccination and
      correlated with T-cell reactivity to the melanoma peptides. Objective clinical
      responses were observed in two patients in the GM-CSF arm and one patient in the
      DC arm. Stable disease was observed in two patients in the GM-CSF arm and one
      patient in the DC arm. CONCLUSION: The high frequency of cytotoxic T-lymphocyte
      responses and the occurrence of clinical tumor regressions support continued
      investigation of multipeptide vaccines administered with GM-CSF in adjuvant.

PMID- 14581427
TI  - Bilateral prophylactic oophorectomy and ovarian cancer screening following
      BRCA1/BRCA2 mutation testing.
AB  - PURPOSE: Despite the widespread availability of genetic testing for BRCA1/BRCA2
      mutations, little is known about the impact of testing on ovarian cancer
      prevention and screening. For mutation testing to effect cancer mortality,
      positive test results must be followed by appropriate behavior change. In this
      study, we prospectively examined the impact of BRCA1/2 testing on the utilization
      of prophylactic oophorectomy and ovarian cancer screening. PARTICIPANTS AND
      METHODS: Participants were 289 high-risk women who underwent genetic counseling
      and testing for alterations in the BRCA1/2 genes. We measured self-reported
      receipt of bilateral prophylactic oophorectomy (BPO) and utilization of CA-125
      and transvaginal ultrasound (TVU) in the year following testing, and examined the
      impact of test results on these outcomes. In addition, we examined the role of
      sociodemographic, medical, family history, and psychological variables on the
      receipt of BPO, CA-125, and TVU. RESULTS: Twenty-seven percent of mutation
      carriers, 5% of uninformative patients, and 2% of noncarriers received a BPO in
      the year following testing. In addition to test results, perceived risk for
      ovarian cancer and family history of ovarian cancer independently predicted
      receipt of BPO. The receipt of a positive test result was associated with
      increased utilization of CA-125 and TVU. Additional predictors included perceived
      risk for ovarian cancer (both CA-125 and TVU) and state anxiety (CA-125).
      CONCLUSION: These results demonstrate the significant behavioral impact of
      receiving a positive BRCA1/2 test result. The increased rate of oophorectomy
      among mutation carriers suggests that testing for BRCA1/2 mutations may
      ultimately impact ovarian cancer mortality.

PMID- 14581428
TI  - Patients presenting with CNS lesions. Case 1. Primary low-grade mucosa-associated
      B-cell lymphoma of the dura.

PMID- 14581429
TI  - Patients presenting with CNS lesions. Case 2. Subdural presentation of recurrent
      breast cancer.

PMID- 14581430
TI  - Patients presenting with CNS lesions. Case 3. Sequential myeloproliferative
      disease and glioblastoma multiforme in a renal transplant recipient.

PMID- 14581431
TI  - Can you cure him, for the baby's sake?

PMID- 14581432
TI  - Corticosteroids underemployment in delayed chemotherapy-induced nausea and emesis
      with poor adherence to American Society of Clinical Oncology guidelines: is this
      a reasonable clinical choice for the elderly?

PMID- 14581433
TI  - Thymidine rescue: an antidote for pemetrexed-related toxicity in the setting of
      acute renal failure.

PMID- 14581435
TI  - Extravasations of oxaliplatin.

PMID- 14581436
TI  - Multicentric study comparing intravesical chemotherapy alone and with local
      microwave hyperthermia for prophylaxis of recurrence of superficial transitional
      cell carcinoma.
AB  - PURPOSE: To compare the efficacy and local toxicity of the intravesical
      instillation of a cytostatic drug versus the same cytostatic agent in combination
      with local hyperthermia as an adjuvant treatment, after complete transurethral
      resection (TURB) of superficial transitional cell carcinoma (TCC) of the bladder.
      PATIENTS AND METHODS: The study was designed as a prospective, multicentric,
      randomized trial. Eighty-three patients suffering from primary or recurrent
      superficial (Ta-T1) TCC of the bladder, after a complete TURB, were randomly
      assigned to receive intravesical instillations of mitomycin C (MMC) alone, for 41
      patients, and MMC in combination with local microwave-induced hyperthermia, for
      42 patients. For the combined approach, a new system, Synergo101-1 (Medical
      Enterprises, Amsterdam, the Netherlands) was used. The effectiveness evaluation
      end points of the study were evaluation of recurrence-free survival and the
      estimated probability of recurrence. The safety evaluation end points included
      subjective and objective side effects and clinical complications. For the
      efficacy end point, Kaplan-Meier analysis was employed, with the log-rank test
      for significance. Minimum follow-up time was 24 months. RESULTS: Of the 83
      randomly assigned patients, 75 completed the study according to the protocol and
      had valid cystoscopy results. Survival analysis of the 75 assessable patients
      demonstrated a highly significant difference in the survival curves in favor of
      thermochemotherapy. Subjective intolerance and clinical complications were
      significantly higher but transient and moderate in the combined treatment group.
      CONCLUSION: In our series, endovesical thermochemotherapy appears to be more
      effective than standard endovesical chemotherapy as an adjuvant treatment for
      superficial bladder tumors at 24-month follow-up, despite an increased but
      acceptable local toxicity.

PMID- 14581437
TI  - Efficacy and safety of rasburicase (recombinant urate oxidase) for the prevention
      and treatment of hyperuricemia during induction chemotherapy of aggressive non
      Hodgkin's lymphoma: results of the GRAAL1 (Groupe d'Etude des Lymphomes de
      l'Adulte Trial on Rasburicase Activity in Adult Lymphoma) study.
AB  - PURPOSE: Hyperuricemia and tumor lysis syndrome are well-known complications
      during induction treatment of aggressive non-Hodgkin's lymphomas (NHLs). Usual
      prophylaxis and treatment of hyperuricemia consist of hydration, alkalinization,
      and administration of allopurinol. This study was designed to evaluate the
      efficacy and the safety of rasburicase (recombinant urate oxidase) in adult
      patients with aggressive NHL during their first cycle of chemotherapy. PATIENTS
      AND METHODS: A total of 100 patients from Groupe d'Etude des Lymphomes de
      l'Adulte centers, with diffuse large B-cell lymphoma (n = 79); anaplastic large
      cell lymphoma (n = 6); peripheral T-cell lymphoma (n = 8); transformation of
      indolent lymphoma (n = 5); Burkitt's lymphoma (n = 1); and lymphoblastic lymphoma
      (n = 1) were enrolled from May 2001 to June 2002. Before chemotherapy, 66% of
      patients had elevated lactate dehydrogenase (LDH), including 28% with LDH above
      1,000 U/mL. Eleven percent of patients were hyperuricemic (uric acid [UA] > 450
      mmol/L or > 7.56 mg/dL). Rasburicase 0.20 mg/kg/d intravenously for 3 to 7 days
      was started the day before or at day 1 of chemotherapy. UA levels were measured 4
      hours after rasburicase injection, then daily during treatment. RESULTS: All
      patients responded to rasburicase, as defined by normalization of UA levels
      maintained during chemotherapy. The control of UA was obtained within 4 hours
      after the first injection of the drug. Creatinine levels and other metabolites
      were also controlled with the administration of rasburicase. No patient exhibited
      increased creatinine levels or required dialysis during chemotherapy. CONCLUSION:
      Rasburicase is the treatment of choice to control UA and prevent tumor lysis
      syndrome in adult patients with aggressive NHL.

PMID- 14581439
TI  - Epidermal growth factor receptor overexpression: the importance of context.

PMID- 14581438
TI  - Combined analysis of two multicenter, randomized, placebo-controlled studies of
      pamidronate disodium for the palliation of bone pain in men with metastatic
      prostate cancer.
AB  - PURPOSE: Bone metastases occur in approximately 80% of patients with advanced
      prostate cancer. Pain is common in these patients. The purpose of this study was
      to evaluate the effect of an intravenous bisphosphonate, pamidronate disodium, on
      pain control in metastatic prostate cancer patients. PATIENTS AND METHODS: Two
      multicenter, double-blind, randomized, placebo-controlled trials were conducted
      in patients with bone pain due to metastatic prostate cancer, with disease
      progression after first-line hormonal therapy. Intravenous pamidronate disodium
      (90 mg) or placebo was administered every 3 weeks for 27 weeks. Efficacy was
      measured via self-reported pain score (Brief Pain Inventory), analgesic use, the
      proportion of patients with a skeletal-related event (SRE; defined as pathologic
      fracture, radiation or surgery to bone, spinal cord compression, or
      hypercalcemia), and a pilot quantitative measurement of mobility. Laboratory
      evaluations included serum prostate-specific antigen, interleukin-6, bone
      alkaline phosphatase, and urinary bone resorption markers. RESULTS: Results of
      the two trials were pooled. There were no sustained significant differences
      between the pamidronate and placebo groups in self-reported pain measurements,
      analgesic use, proportion of patients with an SRE, or mobility at week 9 or 27.
      Urinary bone resorption markers were suppressed in the pamidronate group compared
      with placebo. CONCLUSION: Pamidronate disodium failed to demonstrate a
      significant overall treatment benefit compared with placebo in palliation of bone
      pain or reduction of SREs. Evaluation of more potent bisphosphonates in patients
      with prostate cancer is warranted.

PMID- 14581440
TI  - Adjuvant chemotherapy for breast cancer: how presentation of recurrence risk
      influences decision-making.
AB  - PURPOSE: The purpose of this study was to examine the impact of four methods of
      communicating survival benefits on chemotherapy decisions. We hypothesized that
      the four methods of communicating mathematically equivalent risk information
      would lead to different chemotherapy decisions. METHODS: Each participant
      received two hypothetical scenarios regarding their mother (a postmenopausal
      woman with an invasive, lymph node-negative, hormone receptor-positive breast
      cancer) and was asked to decide whether they would encourage their mother to take
      chemotherapy in addition to surgery and tamoxifen. In the part 1, participants
      received one of four methods of describing the chemotherapy survival benefit: (1)
      relative risk reduction, (2) absolute risk reduction, (3) absolute survival
      benefit, or (4) number needed to treat. In part 2, each participant received all
      four methods. Following each decision, participants were asked to rate their
      confidence and confusion regarding their decision. RESULTS: Participants included
      203 preclinical medical students. In part 1, participants who received relative
      risk reduction information were significantly more likely to endorse
      chemotherapy. In part 2, there were no treatment decision differences when
      participants received all four methods of communicating survival benefits of
      chemotherapy. However, receiving all four methods led to significantly higher
      ratings of confusion. In deciding on endorsing chemotherapy, participants
      understood the information best when presented with data in the absolute survival
      benefit format. CONCLUSION: These results support the hypothesis that the method
      used to present information about chemotherapy influences treatment decisions.
      Absolute survival benefit is the most easily understood method of conveying the
      information regarding benefit of treatment.

PMID- 14581441
TI  - High-dose therapy and autologous peripheral-blood stem-cell transplantation as
      salvage treatment for HIV-associated lymphoma in patients receiving highly active
      antiretroviral therapy.
AB  - PURPOSE: High-dose therapy (HDT) and peripheral-blood stem-cell transplantation
      (PBSCT) in HIV-associated lymphoma (HIV-Ly) has been recently reported in
      selected patients. We describe the results of a multi-institutional program of
      HDT and PBSCT as salvage therapy in HIV-Ly responsive to highly active
      antiretroviral therapy (HAART) in unselected patients. PATIENTS AND METHODS:
      Patients with resistant or relapsed HIV-Ly after first-line chemotherapy (CT)
      underwent PBSC collection after a course of second-line CT or cyclophosphamide
      and granulocyte colony-stimulating factor. Patients with chemotherapy-sensitive
      disease received carmustine, etoposide, cytarabine, and melphalan (BEAM regimen)
      and PBSC reinfusion. Effective HAART was maintained during the entire program.
      RESULTS: Sixteen consecutive patients entered the program. Adequate collection of
      PBSC was obtained in 80% of patients (median CD34+ cells 6.8 x 106/kg). Three
      patients had early progression. Ten patients (62%) received PBSCT with prompt
      engraftment in all patients (neutrophils and platelet engraftment after a median
      of 10 days [range, 8 to 10 days] and 13 days [range, 8 to 18 days],
      respectively). No patients died as a result of opportunistic or other infections
      or treatment-related complications. Eight of nine assessable patients achieved
      complete remission (one patient after radiotherapy for residual disease) and one
      patient achieved partial remission. Two patients experienced relapse and died at
      +10 and +14 months. Six patients are alive and disease free at a median of 8
      months after transplantation. CONCLUSION: Our data confirm that HDT plus PBSCT is
      feasible and active as salvage therapy in HIV-Ly on a multi-institutional basis
      and in unselected HAART-responding patients. HIV infection should no longer
      preclude the opportunity of HDT in patients with lymphoma.

PMID- 14581442
TI  - Bisphosphonates for men with prostate cancer: sifting through the rubble.

PMID- 14581443
TI  - Liver transplantation and hepatocellular carcinoma biology: beginning of the end
      of the era of educated guesses.

PMID- 14581444
TI  - Intravesical therapy for superficial bladder cancer: slow but steady progress.

PMID- 14581445
TI  - Is relative risk reduction a useful measure for patients or families who must
      choose a method of treatment?

PMID- 14581446
TI  - The outcome of liver transplantation in patients with hepatocellular carcinoma in
      the United States between 1988 and 2001: 5-year survival has improved
      significantly with time.
AB  - PURPOSE: We hypothesized that the outcome of liver transplantation in patients
      with hepatocellular carcinoma (HCC) has improved over the past decade because of
      the application of published criteria for patient selection. In this study, we
      compared the outcome of liver transplantation in patients with and without HCC at
      different time periods using the United Network for Organ Sharing data. PATIENTS
      AND METHODS: We excluded children, patients with multiple organ transplantation
      or retransplantation, and those with incomplete survival data. The study period
      was arbitrarily divided into three time intervals: 1987 to 1991, 1992 to 1996,
      and 1997 to 2001. RESULTS: During the study period, 985 patients with HCC (HCC
      group), and 33,339 without HCC underwent liver transplantation (control group).
      Kaplan-Meier patient and graft survivals were significantly lower for the HCC
      group compared with the control group. Cox regression analysis (after adjusting
      for other confounding variables) confirmed a lower patient survival in the HCC
      group (1-year survival, 77.0% v 86.7%; hazard ratio [HR], 1.7; 95% CI, 1.5 to
      2.0; P <.0001) compared with the control group (5-year survival, 48.2% v 74.7%;
      HR, 2.2; 95% CI, 1.9 to 2.4; P <.0001); HCC was an independent predictor of
      survival. Kaplan-Meier analysis showed a significant improvement in 5-year
      patient survival with time in patients with HCC (1987 to 1991, 25.3%; 1992 to
      1996, 46.6%; 1997 to 2001, 61.1%; P <.0001). During the same period, there was
      only minimal improvement in survival among the control group. CONCLUSION: Five
      year survival of patients transplanted for HCC is excellent, with a steady
      improvement in survival over the past decade. It is possible that the published
      criteria for patient selection may have contributed to the better outcome.

PMID- 14581447
TI  - Sorting it out: AP-2 and alternate clathrin adaptors in endocytic cargo
      selection.
AB  - The AP-2 adaptor complex is widely viewed as a linchpin molecule in clathrin
      mediated endocytosis, simultaneously binding both clathrin and receptors. This
      dual interaction couples cargo capture with clathrin coat assembly, but it has
      now been discovered that the association with cargo is tightly regulated.
      Remarkably, AP-2 is not obligatory for all clathrin-mediated uptake, and several
      alternate adaptors appear to perform similar sorting and assembly functions at
      the clathrin bud site.

PMID- 14581448
TI  - Lymphatic endothelium: morphological, molecular and functional properties.
AB  - The lymphatic microvasculature is uniquely adapted for the continuous removal of
      interstitial fluid and proteins, and is an important point of entry for
      leukocytes and tumor cells. The traditional view that lymphatic capillaries are
      passive participants in these tasks is currently being challenged. This overview
      highlights recent advances in our understanding of the molecular mechanisms
      underlying the formation and function of lymphatic vessels.

PMID- 14581449
TI  - Architecture of the budding yeast kinetochore reveals a conserved molecular core.
AB  - How kinetochore proteins are organized to connect chromosomes to spindle
      microtubules, and whether any structural and organizational themes are common to
      kinetochores from distantly related organisms, are key unanswered questions.
      Here, we used affinity chromatography and mass spectrometry to generate a map of
      kinetochore protein interactions. The budding yeast CENP-C homologue Mif2p
      specifically copurified with histones H2A, H2B, and H4, and with the histone H3
      like CENP-A homologue Cse4p, strongly suggesting that Cse4p replaces histone H3
      in a specialized centromeric nucleosome. A novel four-protein Mtw1 complex, the
      Nnf1p subunit of which has homology to the vertebrate kinetochore protein CENP-H,
      also copurified with Mif2p and a variety of central kinetochore proteins. We show
      that Mif2 is a critical in vivo target of the Aurora kinase Ipl1p. Chromatin
      immunoprecipitation studies demonstrated the biological relevance of these
      associations. We propose that a molecular core consisting of CENP-A, -C, -H, and
      Ndc80/HEC has been conserved from yeast to humans to link centromeres to spindle
      microtubules.

PMID- 14581451
TI  - Clathrin promotes incorporation of cargo into coated pits by activation of the
      AP2 adaptor micro2 kinase.
AB  - Endocytic cargo such as the transferrin receptor is incorporated into clathrin
      coated pits by associating, via tyrosine-based motifs, with the AP2 complex.
      Cargo-AP2 interactions occur via the mu2 subunit of AP2, which needs to be
      phosphorylated for endocytosis to occur. The most likely role for mu2
      phosphorylation is in cargo recruitment because mu2 phosphorylation enhances its
      binding to internalization motifs. Here, we investigate the control of mu2
      phosphorylation. We identify clathrin as a specific activator of the mu2 kinase
      and, in permeabilized cells, we show that ligand sequestration, driven by
      exogenous clathrin, results in elevated levels of mu2 phosphorylation.
      Furthermore, we show that AP2 containing phospho-mu2 is mainly associated with
      assembled clathrin in vivo, and that the level of phospho-mu2 is strongly reduced
      in a chicken B cell line depleted of clathrin heavy chain. Our results imply a
      central role for clathrin in the regulation of cargo selection via the modulation
      of phospho-mu2 levels.

PMID- 14581450
TI  - BPAG1n4 is essential for retrograde axonal transport in sensory neurons.
AB  - Disruption of the BPAG1 (bullous pemphigoid antigen 1) gene results in
      progressive deterioration in motor function and devastating sensory
      neurodegeneration in the null mice. We have previously demonstrated that BPAG1n1
      and BPAG1n3 play important roles in organizing cytoskeletal networks in vivo.
      Here, we characterize functions of a novel BPAG1 neuronal isoform, BPAG1n4.
      Results obtained from yeast two-hybrid screening, blot overlay binding assays,
      and coimmunoprecipitations demonstrate that BPAG1n4 interacts directly with
      dynactin p150Glued through its unique ezrin/radixin/moesin domain. Studies using
      double immunofluorescent microscopy and ultrastructural analysis reveal
      physiological colocalization of BPAG1n4 with dynactin/dynein. Disruption of the
      interaction between BPAG1n4 and dynactin results in severe defects in retrograde
      axonal transport. We conclude that BPAG1n4 plays an essential role in retrograde
      axonal transport in sensory neurons. These findings might advance our
      understanding of pathogenesis of axonal degeneration and neuronal death.

PMID- 14581452
TI  - Vps27-Hse1 and ESCRT-I complexes cooperate to increase efficiency of sorting
      ubiquitinated proteins at the endosome.
AB  - Ubiquitin (Ub) attachment to cell surface proteins causes their lysosomal
      degradation by incorporating them into lumenal membranes of multivesicular bodies
      (MVBs). Two yeast endosomal protein complexes have been proposed as Ub-sorting
      "receptors," the Vps27-Hse1 complex and the ESCRT-I complex. We used NMR
      spectroscopy and mutagenesis studies to map the Ub-binding surface for Vps27 and
      Vps23. Mutations in Ub that ablate only Vps27 binding or Vps23 binding blocked
      the ability of Ub to serve as an MVB sorting signal, supporting the idea that
      both the Vps27-Hse1 and ESCRT-I complexes interact with ubiquitinated cargo.
      Vps27 also bound Vps23 directly via two PSDP motifs present within the Vps27 COOH
      terminus. Loss of Vps27-Vps23 association led to less efficient sorting into the
      endosomal lumen. However, sorting of vacuolar proteases or the overall biogenesis
      of the MVB were not grossly affected. In contrast, disrupting interaction between
      Vps27 and Hse1 caused severe defects in carboxy peptidase Y sorting and MVB
      formation. These results indicate that both Ub-sorting complexes are coupled for
      efficient recognition of ubiquitinated cargo.

PMID- 14581453
TI  - DNA damage-induced replication arrest in Xenopus egg extracts.
AB  - Chromosomal replication is sensitive to the presence of DNA-damaging alkylating
      agents, such as methyl methanesulfonate (MMS). MMS is known to inhibit
      replication though activation of the DNA damage checkpoint and through checkpoint
      independent slowing of replication fork progression. Using Xenopus egg extracts,
      we now report an additional pathway that is stimulated by MMS-induced damage. We
      show that, upon incubation in egg extracts, MMS-treated DNA activates a
      diffusible inhibitor that blocks, in trans, chromosomal replication. The
      downstream effect of the inhibitor is a failure to recruit proliferating cell
      nuclear antigen, but not DNA polymerase alpha, to the nascent replication fork.
      Thus, alkylation damage activates an inhibitor that intercepts the replication
      pathway at a point between the polymerase alpha and proliferating cell nuclear
      antigen execution steps. We also show that activation of the inhibitor does not
      require the DNA damage checkpoint; rather, stimulation of the pathway described
      here results in checkpoint activation. These data describe a novel replication
      arrest pathway, and they also provide an example of how subpathways within the
      DNA damage response network are integrated to promote efficient cell cycle arrest
      in response to damaged DNA.

PMID- 14581454
TI  - Formation of stacked ER cisternae by low affinity protein interactions.
AB  - The endoplasmic reticulum (ER) can transform from a network of branching tubules
      into stacked membrane arrays (termed organized smooth ER [OSER]) in response to
      elevated levels of specific resident proteins, such as cytochrome b(5). Here, we
      have tagged OSER-inducing proteins with green fluorescent protein (GFP) to study
      OSER biogenesis and dynamics in living cells. Overexpression of these proteins
      induced formation of karmellae, whorls, and crystalloid OSER structures.
      Photobleaching experiments revealed that OSER-inducing proteins were highly
      mobile within OSER structures and could exchange between OSER structures and
      surrounding reticular ER. This indicated that binding interactions between
      proteins on apposing stacked membranes of OSER structures were not of high
      affinity. Addition of GFP, which undergoes low affinity, antiparallel
      dimerization, to the cytoplasmic domains of non-OSER-inducing resident ER
      proteins was sufficient to induce OSER structures when overexpressed, but
      addition of a nondimerizing GFP variant was not. These results point to a
      molecular mechanism for OSER biogenesis that involves weak homotypic interactions
      between cytoplasmic domains of proteins. This mechanism may underlie the
      formation of other stacked membrane structures within cells.

PMID- 14581455
TI  - Nodal-dependent Cripto signaling promotes cardiomyogenesis and redirects the
      neural fate of embryonic stem cells.
AB  - The molecular mechanisms controlling inductive events leading to the
      specification and terminal differentiation of cardiomyocytes are still largely
      unknown. We have investigated the role of Cripto, an EGF-CFC factor, in the
      earliest stages of cardiomyogenesis. We find that both the timing of initiation
      and the duration of Cripto signaling are crucial for priming differentiation of
      embryonic stem (ES) cells into cardiomyocytes, indicating that Cripto acts early
      to determine the cardiac fate. Furthermore, we show that failure to activate
      Cripto signaling in this early window of time results in a direct conversion of
      ES cells into a neural fate. Moreover, the induction of Cripto activates the
      Smad2 pathway, and overexpression of activated forms of type I receptor ActRIB
      compensates for the lack of Cripto signaling in promoting cardiomyogenesis.
      Finally, we show that Nodal antagonists inhibit Cripto-regulated cardiomyocyte
      induction and differentiation in ES cells. All together our findings provide
      evidence for a novel role of the Nodal/Cripto/Alk4 pathway in this process.

PMID- 14581456
TI  - The Rab8 GTPase selectively regulates AP-1B-dependent basolateral transport in
      polarized Madin-Darby canine kidney cells.
AB  - The AP-1B clathrin adaptor complex plays a key role in the recognition and
      intracellular transport of many membrane proteins destined for the basolateral
      surface of epithelial cells. However, little is known about other components that
      act in conjunction with AP-1B. We found that the Rab8 GTPase is one such
      component. Expression of a constitutively activated GTP hydrolysis mutant
      selectively inhibited basolateral (but not apical) transport of newly synthesized
      membrane proteins. Moreover, the effects were limited to AP-1B-dependent
      basolateral cargo; basolateral transport of proteins containing dileucine
      targeting motifs that do not interact with AP-1B were targeted normally despite
      overexpression of mutant Rab8. Similar results were obtained for a dominant
      negative allele of the Rho GTPase Cdc42, previously implicated in basolateral
      transport but now shown to be selective for the AP-1B pathway. Rab8-GFP was
      localized to membranes in the TGN-recycling endosome, together with AP-1B
      complexes and the closely related but ubiquitously expressed AP-1A complex.
      However, expression of active Rab8 caused a selective dissociation of AP-1B
      complexes, reflecting the specificity of Rab8 for AP-1B-dependent transport.

PMID- 14581457
TI  - The AP-1A and AP-1B clathrin adaptor complexes define biochemically and
      functionally distinct membrane domains.
AB  - Most epithelial cells contain two AP-1 clathrin adaptor complexes. AP-1A is
      ubiquitously expressed and involved in transport between the TGN and endosomes.
      AP-1B is expressed only in epithelia and mediates the polarized targeting of
      membrane proteins to the basolateral surface. Both AP-1 complexes are
      heterotetramers and differ only in their 50-kD mu1A or mu1B subunits. Here, we
      show that AP-1A and AP-1B, together with their respective cargoes, define
      physically and functionally distinct membrane domains in the perinuclear region.
      Expression of AP-1B (but not AP-1A) enhanced the recruitment of at least two
      subunits of the exocyst complex (Sec8 and Exo70) required for basolateral
      transport. By immunofluorescence and cell fractionation, the exocyst subunits
      were found to selectively associate with AP-1B-containing membranes that were
      both distinct from AP-1A-positive TGN elements and more closely apposed to
      transferrin receptor-positive recycling endosomes. Thus, despite the similarity
      of the two AP-1 complexes, AP-1A and AP-1B exhibit great specificity for
      endosomal transport versus cell polarity.

PMID- 14581458
TI  - A dual-functional paramyxovirus F protein regulatory switch segment: activation
      and membrane fusion.
AB  - Many viral fusion-mediating glycoproteins couple alpha-helical bundle formation
      to membrane merger, but have different methods for fusion activation. To study
      paramyxovirus-mediated fusion, we mutated the SV5 fusion (F) protein at conserved
      residues L447 and I449, which are adjacent to heptad repeat (HR) B and bind to a
      prominent cavity in the HRA trimeric coiled coil in the fusogenic six-helix
      bundle (6HB) structure. These analyses on residues L447 and I449, both in intact
      F protein and in 6HB, suggest a metamorphic region around these residues with
      dual structural roles. Mutation of L447 and I449 to aliphatic residues
      destabilizes the 6HB structure and attenuates fusion activity. Mutation of L447
      and I449 to aromatic residues also destabilizes the 6HB structure despite
      promoting hyperactive fusion, indicating that 6HB stability alone does not
      dictate fusogenicity. Thus, residues L447 and I449 adjacent to HRB in
      paramyxovirus F have distinct roles in fusion activation and 6HB formation,
      suggesting this region is involved in a conformational switch.

PMID- 14581459
TI  - Regulation of TrkB receptor tyrosine kinase and its internalization by neuronal
      activity and Ca2+ influx.
AB  - Internalization of the neurotrophin-Trk receptor complex is critical for many
      aspects of neurotrophin functions. The mechanisms governing the internalization
      process are unknown. Here, we report that neuronal activity facilitates the
      internalization of the receptor for brain-derived neurotrophic factor, TrkB, by
      potentiating its tyrosine kinase activity. Using three independent approaches, we
      show that electric stimulation of hippocampal neurons markedly enhances TrkB
      internalization. Electric stimulation also potentiates TrkB tyrosine kinase
      activity. The activity-dependent enhancement of TrkB internalization and its
      tyrosine kinase requires Ca2+ influx through N-methyl-d-aspartate receptors and
      Ca2+ channels. Inhibition of internalization had no effect on TrkB kinase, but
      inhibition of TrkB kinase prevents the modulation of TrkB internalization,
      suggesting a critical role of the tyrosine kinase in the activity-dependent
      receptor endocytosis. These results demonstrate an activity- and Ca2+-dependent
      modulation of TrkB tyrosine kinase and its internalization, and they provide new
      insights into the cell biology of tyrosine kinase receptors.

PMID- 14581462
TI  - Identification and structural characterization of the neuronal luteinizing
      hormone receptor associated with sensory systems.
AB  - The luteinizing hormone receptor (LHR) is a G protein-coupled receptor involved
      in regulation of ovarian and testicular functions. Here we show that the receptor
      is present also in specific areas of the peripheral and central nervous system
      and may thus have a broader functional role than has been anticipated. Full
      length LHR mRNA and two receptor protein species of M(r) 90,000 and 73,000,
      representing mature and precursor forms, respectively, were expressed in adult
      and developing rat nervous tissue, starting at fetal day 14.5. The receptor was
      capable of ligand binding because it was purified by ligand affinity
      chromatography, and human chorionic gonadotropin and LH were able to displace
      (125)I-labeled human chorionic gonadotropin binding to fetal head membranes in a
      dose-dependent manner. Finally, two 5'-flanking sequences ( approximately 2 and 4
      kb) of the rat LHR gene were shown to direct expression of the lacZ reporter to
      specific areas of the peripheral and central nervous system in fetal and adult
      transgenic mice, especially to structures associated with sensory, memory,
      reproductive behavior, and autonomic functions. Importantly, the transgene
      activity was confined to neurons and colocalized with the cytochrome P450 side
      chain cleavage enzyme. Taken together, these results indicate that the neuronal
      LHR is a functional protein, implicating a role in neuronal development and
      function, possibly by means of regulating synthesis of neurosteroids.

PMID- 14581460
TI  - Integrin-linked kinase is required for laminin-2-induced oligodendrocyte cell
      spreading and CNS myelination.
AB  - Early steps in myelination in the central nervous system (CNS) include a
      specialized and extreme form of cell spreading in which oligodendrocytes extend
      large lamellae that spiral around axons to form myelin. Recent studies have
      demonstrated that laminin-2 (LN-2; alpha2beta1gamma1) stimulates oligodendrocytes
      to extend elaborate membrane sheets in vitro (cell spreading), mediated by
      integrin alpha6beta1. Although a congenital LN-2 deficiency in humans is
      associated with CNS white matter changes, LN-2-deficient (dy/dy) mice have shown
      abnormalities primarily within the peripheral nervous system. Here, we
      demonstrate a critical role for LN-2 in CNS myelination by showing that dy/dy
      mice have quantitative and morphologic defects in CNS myelin. We have defined the
      molecular pathway through which LN-2 signals oligodendrocyte cell spreading by
      demonstrating requirements for phosphoinositide 3-kinase activity and integrin
      linked kinase (ILK). Interaction of oligodendrocytes with LN-2 stimulates ILK
      activity. A dominant negative ILK inhibits LN-2-induced myelinlike membrane
      formation. A critical component of the myelination signaling cascade includes LN
      2 and integrin signals through ILK.

PMID- 14581461
TI  - Talin1 is critical for force-dependent reinforcement of initial integrin
      cytoskeleton bonds but not tyrosine kinase activation.
AB  - Cells rapidly transduce forces exerted on extracellular matrix contacts into
      tyrosine kinase activation and recruitment of cytoskeletal proteins to reinforce
      integrin-cytoskeleton connections and initiate adhesion site formation. The
      relationship between these two processes has not been defined, particularly at
      the submicrometer level. Using talin1-deficient cells, it appears that talin1 is
      critical for building early mechanical linkages. Deletion of talin1 blocked laser
      tweezers, force-dependent reinforcement of submicrometer fibronectin-coated beads
      and early formation of adhesion sites in response to force, even though Src
      family kinases, focal adhesion kinase, and spreading were activated normally.
      Recruitment of vinculin and paxillin to sites of force application also required
      talin1. FilaminA had a secondary role in strengthening fibronectin-integrin
      cytoskeleton connections and no role in stretch-dependent adhesion site assembly.
      Thus, force-dependent activation of tyrosine kinases is independent of early
      force-dependent structural changes that require talin1 as part of a critical
      scaffold.

PMID- 14581463
TI  - Outer dense fibers serve as a functional target for Cdk5.p35 in the developing
      sperm tail.
AB  - Cdk5 is ubiquitously expressed in all tissues, but its activators, p35 and p39,
      are principally found in brain, and Cdk5 activity has mostly been associated with
      brain development, particularly neuronal differentiation and migration. Here we
      show that the p35 transcript and protein are also present in the testis, and an
      active Cdk5.p35 complex exists in this tissue as well. Cdk5 and p35 are
      prominently observed in elongating spermatid tails, particularly over the tail
      outer dense fibers (ODF). The appearance of Cdk5.p35 proceeds from the proximal
      to the distal end of elongating spermatids, coinciding with the proximal to
      distal assembly of ODF along the length of the tail axoneme. Incidentally,
      increased Cdk5.p35 activity is observed in isolated elongating spermatids and at
      a time when elongating spermatids appear in the developing testis, suggesting a
      role for Cdk5.p35 in spermiogenesis. The presence of Cdk5 and p35 in ODF isolated
      from rat sperm tails implies a strong association among these proteins. In vitro
      ODF phosphorylation by Cdk5.p35 and decreased in vivo sperm tail ODF
      phosphorylation in p35-deficient mice indicate that Cdk5.p35 is an integral
      component of ODF and that ODF is a functional Cdk5.p35 target in the testis. Our
      results demonstrate for the first time that Cdk5.p35 may participate in the
      regulation of sperm tail development via a mechanism involving ODF
      phosphorylation. Apparently, as in brain development, Cdk5.p35 plays a part in
      testis development.

PMID- 14581464
TI  - Role for ELOVL3 and fatty acid chain length in development of hair and skin
      function.
AB  - Very little is known about the in vivo regulation of mammalian fatty acid chain
      elongation enzymes as well as the role of specific fatty acid chain length in
      cellular responses and developmental processes. Here, we report that the Elovl3
      gene product, which belongs to a highly conserved family of microsomal enzymes
      involved in the formation of very long chain fatty acids, revealed a distinct
      expression in the skin that was restricted to the sebaceous glands and the
      epithelial cells of the hair follicles. By disruption of the Elovl3 gene by
      homologous recombination in mouse, we show that ELOVL3 participates in the
      formation of specific neutral lipids that are necessary for the function of the
      skin. The Elovl3-ablated mice displayed a sparse hair coat, the pilosebaceous
      system was hyperplastic, and the hair lipid content was disturbed with
      exceptionally high levels of eicosenoic acid (20:1). This was most prominent
      within the triglyceride fraction where fatty acids longer than 20 carbon atoms
      were almost undetectable. A functional consequence of this is that Elovl3-ablated
      mice exhibited a severe defect in water repulsion and increased trans-epidermal
      water loss.

PMID- 14581465
TI  - Calpain activation by cooperative Ca2+ binding at two non-EF-hand sites.
AB  - The active site residues in calpain are mis-aligned in the apo, Ca(2+)-free form.
      Alignment for catalysis requires binding of Ca2+ to two non-EF-hand sites, one in
      each of the core domains I and II. Using domain swap constructs between the
      protease cores of the mu and m isoforms (which have different Ca2+ requirements)
      and structural and biochemical characterization of site-directed mutants, we have
      deduced the order of Ca2+ binding and the basis of the cooperativity between the
      two sites. Ca2+ binds first to the partially preformed site in domain I. Knockout
      of this site through D106A substitution eliminates binding to this domain as
      shown by the crystal structure of D106A muI-II. However, at elevated Ca2+
      concentrations this mutant still forms the double salt bridge that links the two
      Ca2+ sites and becomes nearly as active as muI-II. Elimination of the bridge in
      E333A muI-II has a more drastic effect on enzyme action, especially at low Ca2+
      concentrations. Domain II Ca2+ binding appears essential, because Ca(2+)
      coordinating side-chain mutants E302R and D333A have severely impaired muI-II
      activation and activity. The introduction of mutations into the whole
      heterodimeric enzyme that eliminate the salt bridge or Ca2+ binding to domain II
      produce similar phenotypes, suggesting that the protease core Ca2+ switch is
      crucial and cannot be overridden by Ca2+ binding to other domains.

PMID- 14581466
TI  - Lesion bypass by human DNA polymerase mu reveals a template-dependent, sequence
      independent nucleotidyl transferase activity.
AB  - DNA polymerase mu (pol mu), which is related to terminal deoxynucleotidyl
      transferase and DNA polymerase beta, is thought to be involved in non-homologous
      end joining and V(D)J recombination. Pol mu is induced by ionizing radiation and
      exhibits low fidelity. Analysis of translesion replication by purified human pol
      mu revealed that it bypasses a synthetic abasic site with high efficiency, using
      primarily a misalignment mechanism. It can also replicate across two tandem
      abasic sites, using the same mechanism. Pol mu extends primers whose 3'-terminal
      nucleotides are located opposite the abasic site. Most remarkably, this extension
      occurs via a mode of nucleotidyl transferase activity, which does not depend on
      the sequence of the template. This is not due to simple terminal nucleotidyl
      transferase activity, because pol mu is unable to add dNTPs to an oligo(dT)29
      primer or to a blunt end duplex oligonucleotide under standard conditions. Thus,
      pol mu is a dual mode DNA-synthesizing enzyme, which can act as either a
      classical DNA polymerase or as a non-canonical, template-dependent, but sequence
      independent nucleotidyl transferase. To our knowledge, this is the first report
      on a DNA-synthesizing enzyme with such properties. These activities may be
      required for its function in non-homologous end joining in the processing of DNA
      ends prior to ligation.

PMID- 14581467
TI  - NF-kappaB promotes survival during mitotic cell cycle arrest.
AB  - By activating the mitotic checkpoint, anti-microtubule drugs such as nocodazole
      cause mammalian cells to arrest in mitosis and then undergo apoptosis.
      Microtubule depolymerization is rapid and results in the activation of the
      transcription factor NF-kappaB and induction of NF-kappaB-dependent gene
      expression. However, the functional consequence of NF-kappaB activation has
      remained unclear. Evidence has accumulated to suggest that NF-kappaB
      transcriptional activity is required to suppress apoptosis. In the present study,
      we confirm and extend previous findings that microtubule depolymerization leads
      to the rapid activation of NF-kappaB and test the hypothesis that the induction
      of NF-kappaB regulates cell survival during mitotic cell cycle arrest in order to
      define its role. Using a range of functional assays, we have shown that
      microtubule depolymerization correlates with the activation of IKKalpha and
      IKKbeta; the phosphorylation, ubiquitination, and degradation of IkappaBalpha;
      the translocation of native p65 (RelA) into the nucleus; and increased NF-kappaB
      transcriptional activity. By inhibiting either the activation of the IKKs or the
      degradation of IkappaBalpha, we find that the level of apoptosis is significantly
      increased in the mitotically arrested cells. Inhibition of NF-kappaB signaling in
      the nonmitotic cells did not affect their survival. We establish that although NF
      kappaB is activated rapidly in response to microtubule depolymerization, its cell
      survival function is not required until mitotic cell cycle arrest, when the
      mitotic checkpoint is activated and apoptosis is triggered. We conclude that NF
      kappaB may regulate the transcription of one or more antiapoptotic proteins that
      may regulate cell survival during mitotic cell cycle arrest.

PMID- 14581468
TI  - Structural role of PufX in the dimerization of the photosynthetic core complex of
      Rhodobacter sphaeroides.
AB  - Monomeric and dimeric PufX-containing core complexes have been purified from
      membranes of wild-type Rhodobacter sphaeroides. Reconstitution of both samples by
      detergent removal in the presence of lipids leads to the formation of two
      dimensional crystals constituted of dimeric core complexes. Two-dimensional
      crystals were further analyzed by cryoelectron microscopy and atomic force
      microscopy. A projection map at 26-A resolution reveals that core complexes
      assemble in an "S"-shaped dimeric complex. Each core complex is composed of one
      reaction center, 12 light-harvesting 1 alpha/beta-heterodimers, and one PufX
      protein. The light-harvesting 1 assemblies are open with a gap of density of
      approximately 30-A width and surround oriented reaction centers. A maximum
      density is found at the dimer junction. Based on the projection map, a model is
      proposed, in which the two PufX proteins are located at the dimer junction,
      consistent with the finding of dimerization of monomeric core complexes upon
      reconstitution. This localization of PufX in the core complex implies that PufX
      is the structural key for the dimer complex formation rather than a channel
      forming protein for the exchange of ubiquinone/ubiquinol between the reaction
      center and the cytochrome bc1 complex.

PMID- 14581469
TI  - A region of the third intracellular loop of the short form of the D2 dopamine
      receptor dictates Gi coupling specificity.
AB  - The D2 dopamine receptor has two isoforms, the short form (D2s receptor) and the
      long form (D2l receptor), which differ by the presence of a 29-amino acid insert
      in the third cytoplasmic loop. Both the D2s and D2l receptors have been shown to
      couple to members of the G alpha(i) family of G proteins, but whether each
      isoform couples to specific G alpha(i) protein(s) remains controversial. In
      previous studies using G alpha(i) mutants resistant to modification by pertussis
      toxin (G alpha(i)PT), we demonstrated that the D2s receptor couples selectively
      to G alpha(i2)PT and that the D2l receptor couples selectively to G alpha(i3)PT
      (Senogles, S. E. (1994) J. Biol. Chem. 269, 23120-23127). In this study, two
      point mutations of the D2s receptor were created by random mutagenesis (R233G and
      A234T). The two mutant D2s receptors demonstrated pharmacological characteristics
      comparable with those of the wild-type D2s receptor, with similar agonist and
      antagonist binding affinities. We used human embryonic kidney 293 cells stably
      transfected with G alpha(i1)PT, G alpha(i2)PT, or G alpha(i3)PT to measure
      agonist-mediated inhibition of forskolin-stimulated cAMP accumulation before and
      after pertussis toxin treatment. The two mutant D2s receptors demonstrated a
      change in G(i) coupling specificity compared with the wild-type D2s receptor.
      Whereas the wild-type D2s receptor coupled predominantly to G alpha(i2)PT, mutant
      R233G coupled preferentially to G alpha(i3)PT, and mutant A234T coupled
      preferentially to G alpha(i1)PT. These results suggest that this region of the
      third cytoplasmic loop is crucial for determining G(i) protein coupling
      specificity.

PMID- 14581470
TI  - Tumor necrosis factor-alpha inhibits endothelial nitric-oxide synthase gene
      promoter activity in bovine aortic endothelial cells.
AB  - Tumor necrosis factor-alpha (TNF-alpha) has been shown to reduce endothelial
      nitric-oxide synthase (eNOS) gene expression through post-transcriptional
      regulation of mRNA stability. The current study documented an independent effect
      of the cytokine on the eNOS gene promoter. TNF-alpha effected a time- and dose
      dependent reduction in activity of a transiently transfected human -1197 eNOS
      luciferase reporter. This reduction was inhibited by co-transfection of dominant
      negative IKKbeta as well as a nonphosphorylatable constitutively suppressive
      mutant of IkappaB implying involvement of the NFkappaB cascade in the inhibitory
      effect. The locus of the TNF-alpha-dependent inhibition was traced to two Sp1
      binding sites positioned between -109 and -95 and -81 and -67 relative to the
      transcription start site. Electrophoretic mobility shift analysis and
      immunoperturbation studies showed evidence for Sp1 and Sp3 binding to each
      element. TNF-alpha treatment had no effect on the binding pattern to the
      downstream (-81 to -67) site but did suppress association of Sp1 and Sp3 to the
      upstream (-109 to -95) site. Collectively, these data indicate that TNF-alpha
      exerts transcriptional, as well as post-transcriptional, effects on eNOS gene
      expression and suggest a potential mechanism to account for the endothelial
      dysfunction that accompanies disorders such as diabetes mellitus and heart
      failure.

PMID- 14581471
TI  - RhoA binds to the amino terminus of MEKK1 and regulates its kinase activity.
AB  - MEKK1 is a mitogen-activated protein kinase kinase kinase (MAP3K) that can
      regulate the c-Jun amino-terminal kinase (JNK) MAP kinase cascade. MEKK1 is
      comprised of a kinase domain and a long amino-terminal regulatory domain. This
      amino-terminal domain has a scaffold function in that it can assemble modules of
      the JNK and ERK MAP kinase cascades. Recently, we have demonstrated that MEKK1
      binds to p115 Rho GTPase-activating protein, which has GTPase-activating protein
      activity toward RhoA. Thus, we tested whether Rho GTPases interact with the
      regulatory domain of MEKK1. RhoA, but not Rac or Cdc42, binds to a site in the
      aminoterminal one-third of MEKK1, which includes its PHD domain. The interaction
      is prevented by mutation of the essential cysteine in the MEKK1 PHD domain. Rho
      GTP stimulates the kinase activity of full-length MEKK1 as much as 10-fold toward
      MEK4 but does not appear to be ubiquitinated by MEKK1 under conditions that
      result in modification of ERK2. In summary, we have characterized a novel point
      at which Rho GTPases impinge upon the regulation and function of MEKK1.

PMID- 14581472
TI  - Acute ablation of survivin uncovers p53-dependent mitotic checkpoint functions
      and control of mitochondrial apoptosis.
AB  - Survivin is a member of the Inhibitor of Apoptosis gene family that has been
      implicated in cell division and suppression of apoptosis. Here, we show that
      preferential ablation of the nuclear pool of survivin by RNA interference
      produces a mitotic arrest followed by re-entry into the cell cycle and
      polyploidy. Survivin ablation causes multiple centrosomal defects, aberrant
      multipolar spindle formation, and chromatin missegregation, and these phenotypes
      are exacerbated by loss of the cell cycle regulator, p21(Waf1/Cip1) in p21(-/-)
      cells. The mitotic checkpoint activated by loss of survivin is mediated by
      induction of p53 and associated with increased expression of its downstream
      target, p21(Waf1/Cip1). Accordingly, p53(-/-) cells exhibit reduced mitotic
      arrest and enhanced polyploidy upon survivin ablation as compared with their
      p53(+/+) counterparts. Partial reduction of the cytosolic pool of survivin by RNA
      interference sensitizes cells to ultraviolet B-mediated apoptosis and results in
      enhanced caspase-9 proteolytic cleavage, whereas complete ablation of cytosolic
      survivin causes loss of mitochondrial membrane potential and spontaneous
      apoptosis. These data demonstrate that survivin has separable checkpoint
      functions at multiple phases of mitosis and in the control of mitochondrial
      dependent apoptosis.

PMID- 14581473
TI  - Quantitative evaluation of the contribution of weak lysine-binding sites present
      within apolipoprotein(a) kringle IV types 6-8 to lipoprotein(a) assembly.
AB  - During lipoprotein(a) (Lp(a)) assembly, non-covalent interactions between
      apolipoprotein(a) (apo(a)) and low density lipoprotein precede specific disulfide
      bond formation. Studies have shown that the non-covalent step involves an
      interaction between the weak lysine-binding sites (WLBS) present within each of
      apo(a) kringle IV types 6, 7, and 8 (KIV(6-8)), and two lysine residues (Lys(680)
      and Lys(690)) within the NH(2) terminus of the apolipoprotein B-100 (apoB)
      component of low density lipoprotein. In the present study, we introduced single
      point mutations (E56G) into each of the WLBS present in apo(a) KIV(6-8) and
      expressed these mutations in the context of a 17-kringle (17K) recombinant apo(a)
      variant. Single mutations that disrupt the WLBS in KIV(6), KIV(7), and KIV(8), as
      well as mutants that disrupt the WLBS in both KIV(6) and KIV(7), or both KIV(7)
      and KIV(8), were assessed for their ability to form non-covalent and covalent
      Lp(a) complexes. Our results demonstrate that both apo(a) KIV(7) and KIV(8), but
      not KIV(6), are required for maximally efficient non-covalent and covalent Lp(a)
      assembly. Single mutations in the WLBS of KIV(7) or KIV(8) resulted in a 3-fold
      decrease in the affinity of 17K recombinant apo(a) for apoB, and a 20% reduction
      in the rate of covalent Lp(a) formation. Tandem mutations in the WLBS in both
      KIV(7) and KIV(8) resulted in a 13-fold reduction in the binding affinity between
      apo(a) and apoB, and a 75% reduction in the rate of the covalent step of Lp(a)
      formation. We also showed that KIV(7) and KIV(8) specifically bind with high
      affinity to apoB-derived peptides containing Lys(690) or Lys(680), respectively.
      Taken together, our data demonstrate that specific interactions between apo(a)
      KIV(7) and KIV(8) and Lys(680) and Lys(690) in apoB mediate a high affinity non
      covalent interaction between apo(a) and low density lipoprotein, which dictates
      the efficiency of covalent Lp(a) formation.

PMID- 14581474
TI  - Evaluation of the RNA determinants for bacterial and yeast RNase III binding and
      cleavage.
AB  - Bacterial double-stranded RNA-specific RNase III recognizes the A-form of an RNA
      helix with little sequence specificity. In contrast, baker yeast RNase III
      (Rnt1p) selectively recognizes NGNN tetraloops even when they are attached to a B
      form DNA helix. To comprehend the general mechanism of RNase III substrate
      recognition, we mapped the Rnt1p binding signal and directly compared its
      substrate specificity to that of both Escherichia coli RNase III and fission
      yeast RNase III (PacI). Rnt1p bound but did not cleave long RNA duplexes without
      NGNN tetraloops, whereas RNase III indiscriminately cleaved all RNA duplexes.
      PacI cleaved RNA duplexes with some preferences for NGNN-capped RNA stems under
      physiological conditions. Hydroxyl radical footprints indicate that Rnt1p
      specifically interacts with the NGNN tetraloop and its surrounding nucleotides.
      In contrast, Rnt1p interaction with GAAA-capped hairpins was weak and largely
      unspecific. Certain duality of substrate recognition was exhibited by PacI but
      not by bacterial RNase III. E. coli RNase III recognized RNA duplexes longer than
      11 bp with little specificity, and no specific features were required for
      cleavage. On the other hand, PacI cleaved long, but not short, RNA duplexes with
      little sequence specificity. PacI cleavage of RNA stems shorter than 27 bp was
      dependent on the presence of an UU-UC internal loop two nucleotides upstream of
      the cleavage site. These observations suggest that yeast RNase IIIs have two
      recognition mechanisms, one that uses specific structural features and another
      that recognizes general features of the A-form RNA helix.

PMID- 14581475
TI  - A sodium zinc exchange mechanism is mediating extrusion of zinc in mammalian
      cells.
AB  - Zinc influx, driven by a steep inward electrochemical gradient, plays a
      fundamental role in zinc signaling and in pathophysiologies linked to
      intracellular accumulation of toxic zinc. Yet, the cellular transport mechanisms
      that actively generate or maintain the transmembrane gradients are not well
      understood. We monitored Na+-dependent Zn2+ transport in HEK293 cells and
      cortical neurons, using fluorescent imaging. Treatment of the HEK293 cells with
      CaPO4 precipitates induced Na+-dependent Zn2+ extrusion, against a 500-fold
      transmembrane zinc gradient, or zinc influx upon reversal of Na+ gradient, thus
      indicating that Na+/Zn2+ exchange is catalyzing active Zn2+ transport. Depletion
      of intracellular ATP did not inhibit the Na+-dependent Zn2+ extrusion, consistent
      with a mechanism involving a secondary active transporter. Inhibitors of the
      Na+/Ca2+ exchanger failed to inhibit Na+-dependent Zn2+ efflux. In addition, zinc
      transport was unchanged in HEK293 cells heterologously expressing functional
      cardiac or neuronal Na+/Ca2+ exchangers, thus indicating that the Na+/Zn2+
      exchange activity is not mediated by the Na+/Ca2+ exchanger. Sodium-dependent
      zinc exchange, facilitating the removal of intracellular zinc, was also monitored
      in neurons. To our knowledge, the Na+/Zn2+ exchanger described here is the first
      example of a mammalian transport mechanism capable of Na+-dependent active
      extrusion of zinc. Such mechanism is likely to play an important role, not only
      in generating the transmembrane zinc gradients, but also in protecting cells from
      the potentially toxic effects of permeation of this ion.

PMID- 14581476
TI  - Selective disruption of lysosomes in HeLa cells triggers apoptosis mediated by
      cleavage of Bid by multiple papain-like lysosomal cathepsins.
AB  - Increasing evidence suggests that lysosomal proteases are actively involved in
      apoptosis. Using HeLa cells as the model system, we show that selective lysosome
      disruption with L-leucyl-L-leucine methyl ester results in apoptosis,
      characterized by translocation of lysosomal proteases into the cytosol and by the
      cleavage of a proapoptotic Bcl-2-family member Bid. Apoptosis and Bid cleavage,
      but not translocation of lysosomal proteases to the cytosol, could be prevented
      by 15 microM L-trans-epoxysuccinyl(OEt)-Leu-3-methylbutylamide, an inhibitor of
      papain-like cysteine proteases. Incubation of cells with 15 microM N
      benzoyloxycarbonyl-VAD-fluoromethyl ketone prevented apoptosis but not Bid
      cleavage, suggesting that cathepsin-mediated apoptosis in this system is caspase
      dependent. In vitro experiments performed at neutral pH showed that papain-like
      cathepsins B, H, L, S, and K cleave Bid predominantly at Arg(65) or Arg(71). No
      Bid cleavage was observed with cathepsins C and X or the aspartic protease
      cathepsin D. Incubation of full-length Bid treated with cathepsins B, H, L, and S
      resulted in rapid cytochrome c release from isolated mitochondria. Thus, Bid may
      be an important mediator of apoptosis induced by lysosomal disruption.

PMID- 14581477
TI  - Secreted frizzled-related protein 1 (SFRP1) protects fibroblasts from ceramide
      induced apoptosis.
AB  - Secreted frizzled-related proteins (SFRPs) are soluble proteins that have highly
      restricted tissue distribution. Although not fully understood, a role of SFRP1 in
      the regulation of apoptosis has been suggested. Our previous study disclosed a
      much greater level of SFRP1 expression in periodontal ligament fibroblasts
      (PDLFs), which have been suggested to maintain a reduced level of apoptosis
      compared with gingival fibroblasts. We have tested the role of SFRP1 in the
      regulation of fibroblast apoptosis both in vitro and in vivo. Our data showed
      that SFRP1 was significantly up-regulated in cultured human PDLFs during ceramide
      induced apoptosis. In vivo study demonstrated an increased SFRP1 expression in
      mice periodontal ligament during force-induced apoptosis. While inhibition of
      endogenous SFRP1 increased the percentage of cell death in cultured human PDLFs,
      exogenous SFRP1 substantially reduced apoptosis in cultured human gingival
      fibroblasts, which do not maintain a high level of endogenous SFRP1 expression.
      The effect of SFRP1 on apoptosis was linked to the regulation of several
      apoptosis-related genes, including p53, caspase-3, caspase-9, and BCL-2
      interacting killer (BIK). Furthermore our results indicated that the addition of
      exogenous SFRP1 could reduce the level of apoptosis in dermal fibroblasts in
      vivo, and this effect was also linked to the regulation of similar apoptosis
      related genes as observed in in vitro studies. Collectively our results suggest
      that the constitutive up-regulation of SFRP1 could be an adaptive cell survival
      mechanism inherent to functionally specialized fibroblasts, and the addition of
      SFRP1 may contribute to the inhibition of apoptosis in fibroblast-related cells.

PMID- 14581478
TI  - Breast cancer metastasis suppressor 1 (BRMS1) forms complexes with retinoblastoma
      binding protein 1 (RBP1) and the mSin3 histone deacetylase complex and represses
      transcription.
AB  - Breast cancer metastasis suppressor 1 (BRMS1) suppresses metastasis of multiple
      human and murine cancer cells without inhibiting tumorigenicity. By yeast two
      hybrid and co-immunoprecipitation, BRMS1 interacts with retinoblastoma binding
      protein 1 and at least seven members of the mSin3 histone deacetylase (HDAC)
      complex in human breast and melanoma cell lines. BRMS1 co-immunoprecipitates
      enzymatically active HDAC proteins and represses transcription when recruited to
      a Gal4 promoter in vivo. BRMS1 exists in large mSin3 complex(es) of approximately
      1.4-1.9 MDa, but also forms smaller complexes with HDAC1. Deletion analyses show
      that the carboxyl-terminal 42 amino acids of BRMS1 are not critical for
      interaction with much of the mSin3 complex and that BRMS1 appears to have more
      than one binding point to the complex. These results further show that BRMS1 may
      participate in transcriptional regulation via interaction with the mSin3.HDAC
      complex and suggest a novel mechanism by which BRMS1 might suppress cancer
      metastasis.

PMID- 14581479
TI  - Hydrogen peroxide generation induces pp60src activation in human platelets:
      evidence for the involvement of this pathway in store-mediated calcium entry.
AB  - Reactive oxygen species, such as H2O2, have been recognized as intracellular
      messengers involved in several cell functions. Here we report the activation of
      the tyrosine kinase pp60(src) by H2O2, a mechanism required for the activation of
      store-mediated Ca2+ entry (SMCE) in human platelets. Treatment of platelets with
      H2O2 resulted in a time- and concentration-dependent activation of pp60(src).
      Incubation with GF 109203X, a protein kinase C (PKC) inhibitor, prevented H2O2
      induced pp60(src) activation. In contrast, dimethyl-BAPTA loading did not affect
      this response, suggesting that activation of pp60(src) by H2O2 is independent of
      increases in [Ca2+](i). Cytochalasin D, an inhibitor of actin polymerization,
      significantly reduced H2O2-induced pp60(src) activation. We found that platelet
      stimulation with thapsigargin (TG) plus ionomycin (Iono) or thrombin induced
      rapid H2O2 production, a mechanism independent of elevations in [Ca2+](i).
      Treatment of platelets with catalase attenuated TG plus Iono- and thrombin
      induced activation of pp60(src). In addition, catalase as well as the pp60(src)
      inhibitor, PP1, reduced both the activation of SMCE and the coupling between the
      hTrp1 and the IP(3)R type II without having any effect on the maintenance of
      SMCE. Consistent with the role of PKC in the activation of pp60(src) by H2O2, the
      PKC inhibitors GF 109202X and Ro-31-8220 were found to reduced SMCE in platelets.
      This study suggests that platelet activation with TG plus Iono or thrombin is
      associated with H2O2 production, which acts as a second messenger by stimulating
      pp60(src) by a PKC-dependent pathway and is involved in the activation of SMCE in
      these cells.

PMID- 14581480
TI  - Impaired glucose homeostasis in mice lacking the alpha1b-adrenergic receptor
      subtype.
AB  - To assess the role of the alpha1b-adrenergic receptor (AR) in glucose
      homeostasis, we investigated glucose metabolism in knockout mice deficient of
      this receptor subtype (alpha1b-AR-/-). Mutant mice had normal blood glucose and
      insulin levels, but elevated leptin concentrations in the fed state. During the
      transition to fasting, glucose and insulin blood concentrations remained markedly
      elevated for at least 6 h and returned to control levels after 24 h whereas
      leptin levels remained high at all times. Hyperinsulinemia in the post-absorptive
      phase was normalized by atropine or methylatropine indicating an elevated
      parasympathetic activity on the pancreatic beta cells, which was associated with
      increased levels of hypothalamic NPY mRNA. Euglycemic clamps at both low and high
      insulin infusion rates revealed whole body insulin resistance with reduced muscle
      glycogen synthesis and impaired suppression of endogenous glucose production at
      the low insulin infusion rate. The liver glycogen stores were 2-fold higher in
      the fed state in the alpha1b-AR-/- compared with control mice, but were mobilized
      at the same rate during the fed to fast transition or following glucagon
      injections. Finally, high fat feeding for one month increased glucose intolerance
      and body weight in the alpha1b-AR-/-, but not in control mice. Altogether, our
      results indicate that in the absence of the alpha1b-AR the expression of
      hypotalamic NPY and the parasympathetic nervous activity are both increased
      resulting in hyperinsulinemia and insulin resistance as well as favoring obesity
      and glucose intolerance development during high fat feeding.

PMID- 14581481
TI  - Suppressive effect of receptor-interacting protein 140 on coregulator binding to
      retinoic acid receptor complexes, histone-modifying enzyme activity, and gene
      activation.
AB  - Gene induction by retinoic acid (RA) is suppressed by overexpression of receptor
      interacting protein 140 (RIP140). RIP140-mediated suppression was reversed most
      effectively by overexpressing the coactivator p300/CREB-binding protein
      associated factor (P/CAF). Immunoprecipitation demonstrated coexistence of
      holoreceptors complexed with RIP140 or P/CAF. Chromatin immunoprecipitation
      revealed rapid RA-enhanced recruitment of RIP140, but delayed P/CAF recruitment,
      to an RA-targeted promoter in COS-1 cells supplemented with RIP140. In RA-induced
      P19 cells, endogenous RIP140 was rapidly (within 4 h) and significantly recruited
      to both the RARbeta2 and TR2 genes, whereas the peak of endogenous P/CAF
      recruitment occurred much later (48 h) and to a lesser degree. Consistent with
      these observations, significant histone acetylation of endogenous RA receptor
      (RAR) targets was only observed 48 h following RA treatment. In vitro experiments
      confirmed RA-induced transcription from a chromatin template, which was reduced
      by adding RIP140. This study presents evidence for coexistence of multiple RAR
      coregulator complexes and a preferential RA-induced recruitment of RIP140 to
      endogenous RAR-targeted promoters after short term RA treatment, which correlates
      with suppressed induction of RA-regulated gene expression in the presence of
      RIP140.

PMID- 14581482
TI  - Temporal control of NF-kappaB activation by ERK differentially regulates
      interleukin-1beta-induced gene expression.
AB  - In cultured rat vascular smooth muscle cells, sustained activation of ERK is
      required for interleukin-1beta to persistently activate NF-kappaB. Without ERK
      activation, interleukin-1beta induces only acute and transient NF-kappaB
      activation. The present study examined whether the temporal control of NF-kappaB
      activation by ERK could differentially regulate the expression of NF-kappaB
      dependent genes, including inducible nitric oxide synthase (iNOS), cyclooxygenase
      2 (COX-2), vascular cell adhesion molecule-1 (VCAM-1), and manganese-containing
      superoxide dismutase (Mn-SOD). Treatment of vascular smooth muscle cells with
      interleukin-1beta induced the expression of iNOS, COX-2, VCAM-1, and Mn-SOD in a
      time-dependent manner, but with different patterns. Either PD98059 or U0126,
      selective inhibitors of MEK, or overexpression of a dominant negative MEK-1
      inhibited interleukin-1beta- induced ERK activation and the expression of iNOS
      and COX-2 but had essentially no effect on the expression of VCAM-1 and Mn-SOD.
      The expression of these genes was inhibited when NF-kappaB activation was down
      regulated by MG132, a proteasome inhibitor, or by overexpression of an I
      kappaBalpha mutant that prevented both the transient and the persistent
      activation of NF-kappaB. Inhibition of ERK did not affect interleukin-1beta
      induced I-kappaBalpha phosphorylation and degradation but attenuated I-kappaBbeta
      degradation. Thus, although NF-kappaB activation was essential for interleukin
      1beta induction of each of the proteins studied, gene expression was
      differentially regulated by ERK and by the duration of NF-kappaB activation.
      These results reveal a novel functional role for ERK as an important temporal
      regulator of NF-kappaB activation and NF-kappaB-dependent gene expression.

PMID- 14581483
TI  - Complementary roles for Rpn11 and Ubp6 in deubiquitination and proteolysis by the
      proteasome.
AB  - Substrates destined for degradation by the 26 S proteasome are labeled with
      polyubiquitin chains. These chains can be dismantled by deubiquitinating enzymes
      (DUBs). A number of reports have identified different DUBs that can hydrolyze
      ubiquitin from substrates bound to the proteasome. We measured deubiquitination
      by both isolated lid and base-core particle subcomplexes, suggesting that at
      least two different DUBs are intrinsic components of 26 S proteasome holoenzymes.
      In agreement, we find that highly purified proteasomes contain both Rpn11 and
      Ubp6, situated within the lid and base subcomplexes, respectively. To study their
      relative contributions, we purified proteasomes from a mutant in the putative
      metalloprotease domain of Rpn11 and from a ubp6 null. Interestingly, in both
      preparations we observed slower deubiquitination rates, suggesting that Rpn11 and
      Ubp6 serve complementary roles. In accord, the double mutant is synthetically
      lethal. In contrast to WT proteasomes, proteasomes lacking the lid subcomplex or
      those purified from the rpn11 mutant are less sensitive to metal chelators,
      supporting the prediction that Rpn11 may be a metalloprotein. Treatment of
      proteasomes with ubiquitin-aldehyde or with cysteine modifiers also inhibited
      deubiquitination but simultaneously promoted degradation of a monoubiquitinated
      substrate along with the ubiquitin tag. Degradation is unique to 26 S proteasome
      holoenzymes; we could not detect degradation of a ubiquitinated protein by
      "lidless" proteasomes, although they were competent for deubiquitination. The
      fascinating observation that a single ubiquitin moiety is sufficient for
      targeting an otherwise stable substrate to proteasomes exposes how rapid
      deubiquitination of poorly ubiquitinated substrates may counteract degradation.

PMID- 14581484
TI  - Induction of endothelial cell activation by a triple helical alpha2beta integrin
      ligand, derived from type I collagen alpha1(I)496-507.
AB  - Endothelial cell activation involves the elevated expression of cell adhesion
      molecules, chemoattractants, chemokines, and cytokines. These expression profiles
      may be regulated by integrin-mediated cell signaling pathways. In the current
      study, an alpha2beta1 integrin triple helical peptide ligand derived from type I
      collagen residues alpha1(I)496-507 was examined for induction of human aortic
      endothelial cell (HAEC) activation. In addition, a "miniextracellular matrix"
      composed of a mixture of the alpha1(I)496-507 ligand and a second, alpha-helical
      ligand incorporating the endothelial cell proliferating region of SPARC (secreted
      protein acidic and rich in cysteine) was studied for induction of HAEC
      activation. Following HAEC adhesion to alpha1(I)496-507, mRNA expression of E
      selectin-1, vascular and intercellular cell adhesion molecules-1, and monocytic
      chemoattractant protein-1 was stimulated, whereas that of endothelin-1 was
      inhibited. Enzyme-linked immunosorbent assay analysis demonstrated that E
      selectin-1 and monocytic chemoattractant protein-1 expression was also
      stimulated, whereas endothelin-1 protein expression diminished. Engagement of the
      alpha2beta1 integrin initiated a HAEC response similar to that of tumor necrosis
      factor-alpha-induced HAECs but was not sufficient to induce an inflammatory
      response. Addition of the SPARC119-122 region had only a slight effect on HAEC
      activation. Other cell-extracellular matrix interactions appear to be required to
      elicit an inflammatory response. The alpha2beta1 integrin specific triple helical
      peptide ligand described herein represents a more general in vitro model system
      by which gene expression and protein production profiles induced by binding to a
      single cellular receptor type can be quantified.

PMID- 14581485
TI  - The transcriptional repressor STRA13 regulates a subset of peripheral circadian
      outputs.
AB  - Central and peripheral mammalian circadian clocks regulate a variety of
      behavioral and physiological processes through the rhythmic transcription of
      hundreds of clock-controlled genes. The circadian expression of many
      transcriptional regulators suggests that a major part of this circadian gene
      network is indirectly regulated by clock genes. Here we show that the basic helix
      loop-helix transcriptional repressor Stra13 is rhythmically expressed in mouse
      peripheral organs. The circadian transcription of Stra13 is mediated by a
      response element recognized by the CLOCK-BMAL1 heterodimer and located in the
      proximal promoter region. CLOCK-BMAL1-dependent activation of Stra13 is strongly
      repressed by CRY1 and also by STRA13 itself. To determine putative Stra13 output
      genes, we performed microarray analyses of differential gene expression in the
      liver between wild type and Stra13-/- mice and identified 42 target genes
      including a subset of 20 previously known as clock-controlled genes. Importantly,
      we demonstrate that circadian gene expression of the serum protein insulin-like
      growth factor-binding protein 1 and of the NKG2D receptor ligand retinoic acid
      early transcript was suppressed in Stra13-/- mice. These biochemical and genetic
      data establish a role for the basic helix-loop-helix repressor STRA13 as a
      circadian output regulator in the periphery.

PMID- 14581486
TI  - A fluorescent probe-labeled Escherichia coli aspartate transcarbamoylase that
      monitors the allosteric conformational state.
AB  - A new system has been developed capable of monitoring conformational changes of
      the 240s loop of aspartate transcarbamoylase, which are tightly correlated with
      the quaternary structural transition, with high sensitivity in solution. Pyrene,
      a fluorescent probe, was conjugated to residue 241 in the 240s loop of aspartate
      transcarbamoylase to monitor changes in conformation by fluorescence
      spectroscopy. Pyrene maleimide was conjugated to a cysteine residue on the 240s
      loop of a previously constructed double catalytic chain mutant version of the
      enzyme, C47A/A241C. The pyrene-labeled enzyme undergoes the normal T to R
      structural transition, as demonstrated by small-angle x-ray scattering. Like the
      wild-type enzyme, the pyrene-labeled enzyme exhibits cooperativity toward
      aspartate, and is activated by ATP and inhibited by CTP at subsaturating
      concentrations of aspartate. The binding of the bisubstrate analogue N
      (phosphonoacetyl)-l-aspartate (PALA), or the aspartate analogue succinate, in the
      presence of saturating carbamoyl phosphate, to the pyrenelabeled enzyme caused a
      sigmoidal change in the fluorescence emission. Saturation with ATP and CTP (in
      the presence of either subsaturating amounts of PALA or succinate and carbamoyl
      phosphate) caused a hyperbolic increase and decrease, respectively, in the
      fluorescence emission. The half-saturation values from the fluorescence
      saturation curves and kinetic saturation curves were, within error, identical.
      Fluorescence and small-angle x-ray scattering stopped-flow experiments, using
      aspartate and carbamoyl phosphate, confirm that the change in excimer
      fluorescence and the quaternary structure change correlate. These results in
      conjunction with previous studies suggest that the allosteric transition involves
      both global and local conformational changes and that the heterotropic effect of
      the nucleotides may be exerted through local conformational changes in the active
      site by directly influencing the conformation of the 240s loop.

PMID- 14581487
TI  - Inhibition of phosphatidylinositol 3-kinase- and ERK MAPK-regulated protein
      synthesis reveals the pro-apoptotic properties of CD40 ligation in carcinoma
      cells.
AB  - CD40, a member of the tumor necrosis factor receptor superfamily, is frequently
      expressed in carcinomas where its stimulation results in induction of apoptosis
      when de novo protein synthesis is inhibited. The requirement of protein synthesis
      inhibition for efficient killing suggests that CD40 transduces potent survival
      signals capable of suppressing its pro-apoptotic effects. We have found that
      inhibition of CD40 signaling on the phosphatidylinositol 3-kinase (PI3K) and ERK
      MAPK but not on the p38 MAPK axis disrupts this balance and sensitizes carcinoma
      cells to CD40-mediated cell death. The CD40-mediated PI3K and ERK activities were
      found to converge on the regulation of protein synthesis in carcinoma cells via a
      pathway involving the activation of p90 ribosomal S6 kinase (p90Rsk) and p70S6
      kinases, upstream of the translation elongation factor eEF2. In addition, CD40
      ligation was found to mediate a PI3K- and mammalian target of rapamycin (mTOR)
      dependent phosphorylation of 4E-BP1 and its subsequent dissociation from the mRNA
      cap-binding protein eIF4E as well as an ERK-dependent phosphorylation of eIF4E,
      thus promoting translation initiation. Concomitantly, the antiapoptotic protein
      cFLIP was found to be induced in CD40 ligand-stimulated carcinoma cells in a PI3K
      , ERK-, and mammalian target of rapamycin (mTOR)-dependent manner and down
      regulation of cFLIPS expression sensitized to CD40-mediated carcinoma cell death.
      These data underline the significance of the PI3K and ERK pathways in controlling
      the balance between CD40-mediated survival and death signals through the
      regulation of the protein synthesis machinery. Pharmacological agents that target
      this machinery or its upstream kinases could, therefore, be exploited for CD40
      based tumor therapy.

PMID- 14581490
TI  - Neurophysiology of erectile function: androgenic effects.

PMID- 14581488
TI  - Ultraviolet A-induced production of matrix metalloproteinase-1 is mediated by
      macrophage migration inhibitory factor (MIF) in human dermal fibroblasts.
AB  - Matrix metalloproteinases (MMPs) are thought to be responsible for dermal
      photoaging in human skin. In the present study, we evaluated the involvement of
      macrophage migration inhibitory factor (MIF) in MMP-1 expression under
      ultraviolet A (UVA) irradiation in cultured human dermal fibroblasts. UVA (20
      J/cm(2)) up-regulates MIF production, and UVA-induced MMP-1 mRNA production is
      inhibited by an anti-MIF antibody. MIF (100 ng/ml) was shown to induce MMP-1 in
      cultured human dermal fibroblasts. We found that MIF (100 ng/ml) enhanced MMP-1
      activity in cultured fibroblasts assessed by zymography. Moreover, we observed
      that fibroblasts obtained from MIF-deficient mice were much less sensitive to UVA
      regarding MMP-13 expression than those from wild-type BALB/c mice. Furthermore,
      after UVA irradiation (10 J/cm(2)), dermal fibroblasts of MIF-deficient mice
      produced significantly decreased levels of MMP-13 compared with fibroblasts of
      wild-type mice. Next we investigated the signal transduction pathway of MIF. The
      up-regulation of MMP-1 mRNA by MIF stimulation was found to be inhibited by a PKC
      inhibitor (GF109203X), a Src-family tyrosine kinase inhibitor (herbimycin A), a
      tyrosine kinase inhibitor (genistein), a PKA inhibitor (H89), a MEK inhibitor
      (PD98089), and a JNK inhibitor (SP600125). In contrast, the p38 inhibitor
      (SB203580) was found to have little effect on expression of MMP-1 mRNA. We found
      that PKC-pan, PKC alpha/beta II, PKC delta (Thr505), PKC delta (Ser(643)), Raf,
      and MAPK were phosphorylated by MIF. Moreover, we demonstrated that
      phosphorylation of PKC alpha/beta II and MAPK in response to MIF was suppressed
      by genistein, and herbimycin A as well as by transfection of the plasmid of C
      terminal Src kinase. The DNA binding activity of AP-1 was significantly up
      regulated 2 h after MIF stimulation. Taken together, these results suggest that
      MIF is involved in the up-regulation of UVA-induced MMP-1 in dermal fibroblasts
      through PKC-, PKA-, Src family tyrosine kinase-, MAPK-, c-Jun-, and AP-1
      dependent pathways.

PMID- 14581491
TI  - Corpus cavernosum smooth muscle physiology: a role for sex hormones?

PMID- 14581493
TI  - Molecular biology and pharmacology of PDE-5-inhibitor therapy for erectile
      dysfunction.

PMID- 14581494
TI  - Testosterone, sexuality, and erectile function in aging men.

PMID- 14581492
TI  - Endothelial dysfunction in erectile dysfunction: role of the endothelium in
      erectile physiology and disease.

PMID- 14581495
TI  - Is hypogonadism a risk factor for sexual dysfunction?

PMID- 14581496
TI  - An update on the PDE-5 inhibitors (PDE-5i).

PMID- 14581497
TI  - Optimizing response to phosphodiesterase therapy: impact of risk-factor
      management.

PMID- 14581498
TI  - Diagnosing male factor infertility using microarrays.

PMID- 14581499
TI  - Tales from the tail: what do we really know about sperm motility?

PMID- 14581500
TI  - Action needed: an affirmative change in affirmative action policies.

PMID- 14581501
TI  - "The andrology lab corner" beginnings.

PMID- 14581502
TI  - Testicular sperm retrieval in the management of chemotherapy induced azoospermia.

PMID- 14581503
TI  - Molecular barr bodies: methylation-specific PCR of the human X-linked gene FMR-1
      for diagnosis of Klinefelter syndrome.

PMID- 14581504
TI  - Re: seasonal variation and age-related changes in human semen parameters.

PMID- 14581507
TI  - Characterization of membrane rafts isolated from rat sertoli cell cultures:
      caveolin and flotillin-1 content.
AB  - Membrane rafts from Sertoli cell cultures were isolated as detergent-insoluble
      glycosphingolipid-enriched (DIG) fractions on the basis of their enriched content
      of glycosphingolipids and cholesterol and the resulting insolubility in 1% Triton
      X-100 and their low buoyant density. Because lipid rafts have been implicated in
      numerous cell functions, including cell signaling and sites for actin/membrane
      attachment, studies were initiated to characterize Sertoli cell rafts. This study
      reports the distribution of the raft structural proteins, caveolin and flotillin
      1, implicated in raft microdomain organization. Methods employed included the
      immunoblotting of cell lysates and detergent-insoluble glycosphingolipid-enriched
      (DIG) fractions, the immunofluorescent microscopy of peritubular myoid cell (PMC)
      cultures and cryostat-sectioned testis, and the immunohistochemical staining of
      paraffin-embedded sections following microwave antigen retrieval techniques.
      Sertoli cells and Sertoli DIG fractions were found to lack the common raft
      associated protein, caveolin, a marker protein for caveolae, but they are
      enriched in the 48-kd protein, flotillin-1, a protein also implicated in raft
      formation, cell signaling, and cell motility. Since the primary cell contaminant
      of Sertoli cell cultures is the PMC, these cells, along with spermatogenic cell
      fraction (SPGC), were also examined for caveolin and flotillin-1 content. The
      PMCs contained significant concentrations of both caveolin and flotillin-1. PMCs
      in culture exhibited a punctate caveolin staining pattern at the cell surface
      characteristic of a caveolar location. These data support the idea that the
      pinocytotic vesicles observed in PMCs are caveolae. PMCs also show a perinuclear
      location for caveolin characteristic of a Golgi location. Cryostat sections of
      rat testis showed a marked concentration of caveolin in the PMCs. The PMC
      location of caveolin was also confirmed by the immunohistochemical staining of
      sections from paraffin-embedded rat testis following microwave antigen retrieval
      techniques. Similar experiments showed a more ubiquitous, stage-specific
      distribution of flotillin-1 among testicular cell types.

PMID- 14581508
TI  - 5-aza-2'-deoxycytidine induces alterations in murine spermatogenesis and
      pregnancy outcome.
AB  - Because of the ability of cytidine analogues, such as 5-aza-2'-deoxycytidine, to
      incorporate into DNA and lead to decreases in DNA methylation, there has recently
      been renewed interest in using these drugs in anticancer therapy. To determine
      the effects of paternal 5-aza-2'-deoxycytidine treatment on spermatogenesis and
      progeny outcome in the mouse and whether effects are modulated by decreased
      levels of the predominant DNA methyltransferase, DNMT1, adult Dnmt1(+/+) and
      Dnmt1-deficient (Dnmt1(c/+)) male mice were treated with 5-aza-2'-deoxycytidine
      for 7 weeks, which resulted in dose-dependent decreases in testicular weight, an
      increase in histological abnormalities, and a decline in sperm counts, with no
      apparent effect on androgen status. Testes of Dnmt1(c/+) mice, however, were less
      severely affected by 5-aza-2'-deoxycytidine than were those of wild-type mice.
      The exposure of Dnmt1(+/+) male mice to even low doses of 5-aza-2'-deoxycytidine
      followed by mating elicited significantly reduced pregnancy rates and elevated
      preimplantation loss in females. Dnmt1 deficiency, however, protected against
      such drug-induced decreases in pregnancy rate but not preimplantation loss.
      Altered DNA methylation or DNMT1 activity may explain such adverse effects,
      because treatment resulted in dose-dependent decreases in the global methylation
      of sperm DNA. Thus, in the mouse, paternal administration of 5-aza-2'
      deoxycytidine interferes with normal male germ cell development and results in
      reduced fertility, whereas lowering DNMT1 levels appears to partially protect the
      seminiferous epithelium from deleterious drug effects.

PMID- 14581509
TI  - Viability and protein phosphorylation patterns of boar spermatozoa agglutinated
      by treatment with a cell-permeable cyclic adenosine 3',5'-monophosphate analog.
AB  - Boar spermatozoa become agglutinated with one another at the head when their
      intracellular cyclic adenosine 3',5'-monophosphate (cAMP)-signaling cascades are
      activated in the head. The aim of the present study is to examine viability and
      protein phosphorylation patterns of cAMP-dependently agglutinated boar
      spermatozoa. Ejaculated spermatozoa were washed and then incubated in a modified
      Krebs-Ringer HEPES medium containing polyvinyl alcohol (mKRH-PVA) plus 0.1 mM Sp
      5,6-dichloro-1-beta-D-ribofuranosyl-benzimidazole-3',5'-monophosphorothioate
      (cBiMPS, a cell-permeable cAMP analog) at 38.5 degrees C up to 180 minutes.
      Aliquots of the sperm suspensions were recovered after various incubation periods
      and then used to examine the state of agglutination, the viability by SYBR14-PI
      staining and motility assay, and the state of protein phosphorylation by Western
      blotting and indirect immunofluorescence. In the control samples incubated
      without cBiMPS for 180 minutes, less than 30% of the total spermatozoa were
      agglutinated with one another at the heads, and more than 70% of the agglutinated
      spermatozoa were propidium iodide (PI)-positive (dead). However, the incubation
      with cBiMPS rapidly increased the percentages of head-to-head agglutinated
      spermatozoa to approximately 60% within 30 minutes, but did not significantly
      change them thereafter. In the samples incubated with cBiMPS for 180 minutes,
      moreover, the percentages of PI-positive cells of the agglutinated spermatozoa
      (approximately 30%) were significantly lower than those obtained in the control
      samples (more than 70%). This result was supported by the observation that the
      percentages of motile cells of the agglutinated spermatozoa were much higher in
      the samples incubated with cBiMPS for 180 minutes than in the control samples
      incubated without cBiMPS. As revealed by Western blotting and indirect
      immunofluorescence, cBiMPS-induced serine/threonine phosphorylation of the
      proteins (eg, >220 kd, 220 kd, 180 kd, 84 kd, and 54 kd) appeared mainly in the
      connecting and principal pieces of both agglutinated and free spermatozoa within
      30 minutes, and additional phosphorylation occurred in the middle piece later
      than 30 minutes. Moreover, tyrosine phosphorylation of the proteins (eg, >220 kd,
      190 kd, 93 kd, 59 kd, 54 kd, and 32 kd) was induced intensely in the connecting
      and principal pieces and moderately in the middle piece of almost one half of the
      agglutinated spermatozoa after incubation with cBiMPS for more than 30 minutes,
      but rarely in those of the free spermatozoa. These findings are consistent with
      the following suggestions: activation of the cAMP-signaling cascades leads to
      rapid (within 30 minutes) head-to-head agglutination in live spermatozoa; rapid
      (within 30 minutes) protein serine/threonine phosphorylation in the connecting
      and principal pieces of both cAMP-dependently agglutinated and free spermatozoa
      and subsequent (later than 30 minutes) phosphorylation in the middle piece of
      them; and slow (later than 30 minutes) protein tyrosine phosphorylation in the
      connecting, middle, and principal pieces of the cAMP-dependently agglutinated
      spermatozoa. Based on these suggestions, we conclude that many of cAMP
      dependently agglutinated spermatozoa are live cells in which cAMP-signaling
      cascades leading to protein serine/threonine and tyrosine phosphorylation are
      activated in the whole flagellum.

PMID- 14581510
TI  - A transgenic analysis of mouse lactate dehydrogenase C promoter activity in the
      testis.
AB  - Transcription of the mouse testis-specific lactate dehydrogenase c (mldhc) gene
      is limited to cells of the germinal epithelium. Cloning and analysis of the mldhc
      promoter revealed that a 100-bp core promoter was able to regulate testis
      specific transcription in vitro and in transgenic mice. Surprisingly, expression
      of the reporter in transgenic testes was limited to pachytene spermatocytes,
      whereas native LDH-C(4) was detected in pachytene and all later germ cells. To
      locate additional regulatory sequence that could recapitulate the native LDH-C(4)
      distribution pattern, we investigated the contribution of 5' and 3' flanking
      sequences to the regulation of LDH-C(4) expression. We found that transcription
      factor YY1 binds to the mldhc promoter, that the mldhc 3' untranslated sequence
      does not permit a postmeiotic expression of a beta-galactosidase reporter in
      transgenic mice, and that native mldhc mRNA is predominately meiotic, with only a
      low level of postmeiotic distribution. Our results suggest that the high level of
      LDH-C(4) in postmeiotic cells results from mRNA and protein stability.

PMID- 14581511
TI  - Evaluation of chromosome breakage and DNA integrity in sperm: an investigation of
      remote semen collection conditions.
AB  - Collection of ejaculated semen at a remote site (outside of the laboratory) would
      facilitate participation rates and geographic diversity in reproductive
      epidemiology studies. Our study addressed concerns that remote collection and
      overnight mail return might induce chromosome/DNA damage. We collected semen from
      10 healthy men. Part of each sample was snap frozen in liquid nitrogen and the
      rest held at 22 +/- 1 degrees C for 24 hours in a transport container (simulating
      ambient temperature during overnight return) then snap frozen. DNA breakage and
      fragmentation were measured using tandem-label sperm-fluorescence in situ
      hybridization (FISH), terminal deoxynucleotidyl transferase-mediated dUTP nick
      end-labeling (TUNEL), and neutral comet assay. Tandem-label sperm-FISH and TUNEL
      detected no statistically significant difference between sperm fresh frozen (FF)
      and those frozen after 24 hours (F24). The mean frequency of chromosome breakage
      per 10 000 cells scored in sperm-FISH for FF and F24 was 10.5 +/- 1.3 breaks and
      11.2 +/- 1.1 breaks, respectively (P =.69, Student's t test). The mean frequency
      of TUNEL-positive cells per 2000 cells scored in FF and F24 was 136 +/- 29 and
      213 +/- 28 cells, respectively, which approached but did not reach statistical
      significance (P = 0.07, Student's t test). The neutral comet assay detected a
      statistically significant difference in DNA strand breakage between the 2 groups
      (percentage of DNA in the tail P = 0.037; tail moment P = 0.006; and tail length
      P = 0.033, all Student's t test). The mean frequency of damage denoted by tail
      length in micro m per 100 cells scored in FF and F24 was 175.0 +/- 15.5 and 152.2
      +/- 17.6 micro m, respectively. Tandem-label sperm-FISH, TUNEL, and neutral comet
      assay are useful analytical techniques for laboratory-based studies of human
      sperm genomic integrity; however, for field studies incorporating the
      nonrefrigerated return of semen after 24 hours, only chromosome breakage at a
      level that can be detected using tandem-label sperm-FISH was unaffected. TUNEL
      and neutral comet assay need further study before they are used in specimens
      collected at remote sites and transported to a central laboratory.

PMID- 14581512
TI  - Utility of the nitroblue tetrazolium reduction test for assessment of reactive
      oxygen species production by seminal leukocytes and spermatozoa.
AB  - The purpose of this study was to evaluate the ability of spermatozoa and
      leukocytes in semen to produce reactive oxygen species (ROS) by using nitroblue
      tetrazolium (NBT) staining and to examine the association between NBT staining
      and levels of ROS as measured by chemiluminescence. Twenty-one infertility
      patients (leukocytospermia; n = 8; nonleukocytospermia, n = 13) and 9 healthy
      donors were included. Standard semen analysis and density gradient centrifugation
      were performed to test NBT staining, ROS, and total antioxidant capacity. A ROS
      total antioxidant capacity (ROS-TAC) score was calculated by using principal
      component analysis. In the leukocytospermic group, after separation on a density
      gradient, the percentage of NBT-positive staining was significantly higher in
      sperm suspensions contaminated with leukocytes (median [25th, 75th percentiles];
      70% [61%, 79%]) compared to the nonleukocytospermic group (14.5% [9%, 25.5%]; P
      =.03) and donors (7% [3%, 11%]; P =.02), respectively. A strong positive
      correlation was seen between levels of ROS in whole ejaculates and NBT-positive
      staining in leukocytes (r = 0.59; P <.0006) and in leukocyte fractions (r = 0.72;
      P <.0001) after density gradient separation. Similarly, ROS was positively
      correlated with excessive cytoplasmic retention in spermatozoa from whole
      ejaculates and abnormal spermatozoa after separation on density gradients (r =
      0.72; P <.0001). The ROS-TAC score was inversely correlated with NBT staining in
      leukocytes in whole ejaculates (r = -0.960, P <.0007) and in both leukocyte
      fractions (r = -0.39; P <.04) and spermatozoa with cytoplasmic retention (r = 
      0.38; P <.04). Our results indicate that the NBT reduction test can be used to
      assess the contribution of seminal leukocytes and defective spermatozoa towards
      ROS generation in semen. Levels of ROS assessed by chemiluminescence assay are
      strongly correlated with the results of NBT staining.

PMID- 14581513
TI  - The ratio of second to fourth digit length in azoospermic males undergoing
      surgical sperm retrieval: predictive value for sperm retrieval and on wubsequent
      fertilization and pregnancy rates in IVF/ICSI cycles.
AB  - The differentiation of the urogenital system and the appendicular skeleton in
      vertebrates is under the control of Homeobox (Hox) genes. It has been shown that
      this common control of digit and gonad differentiation has connected the pattern
      of digit formation to spermatogenesis and prenatal hormone concentrations in
      males. We wished to establish whether digit patterns, particularly the ratio
      between the lengths of the second and fourth digit in males (2D : 4D), was
      related to spermatogenesis and, more specifically, the presence of spermatozoa in
      testicular biopsies from azoospermic men undergoing surgical sperm retrieval.
      Forty-four men were recruited, of whom 16 were diagnosed with nonobstructive
      azoospermia and 4 with congenital bilateral absence of the vas deferens, and 24
      previously fertile men were azoospermic after previous vasectomy. Our results
      show that men with previous fertility or of an acquired form of azoospermia had
      significantly lower 2D : 4D ratios than men with nonobstructive azoospermia. In
      nonobstructive azoospermia, there was a significantly lower 2D : 4D ratio on the
      left side in men who had successful retrieval than those with unsuccessful
      retrieval. For these men who had a successful retrieval, none had a 2D : 4D ratio
      more than 1 on the left side, whereas 4 of 7 men in whom sperm was not found had
      a 2D : 4D ratio greater than 1. On successful sperm retrieval, subsequent
      fertilization and clinical pregnancy rates were unaffected by 2D : 4D ratios.

PMID- 14581514
TI  - Quantification of seminal plasma motility inhibitor/semenogelin in human seminal
      plasma.
AB  - Semenogelin I and II (Sg I and II) are the major components of human semen
      coagulum. The protein is rapidly cleaved after ejaculation by the chymotrypsin
      like protease prostate-specific antigen (PSA), which results in the liquefaction
      of the semen coagulum and the progressive release of motile spermatozoa. One of
      the cleavage products of the protein, a 14-kDa protein, is a sperm motility
      inhibitor (seminal plasma motility inhibitor [SPMI]). We developed a monoclonal
      antibody (mAb) that is specific to the fragment of Sgs, SPMI, and a sandwich
      enzyme-linked immunosorbent assay (ELISA) system for the quantification of Sgs
      using this mAb. Then, we measured SPMI/Sg levels in human seminal plasma from
      healthy male volunteers (n = 100, aged 18-24 years). The mean level of SPMI/Sg in
      seminal plasma was 19 +/- 13 mg/mL (range, 4-68 mg/mL). Log-transformed SPMI/Sg
      levels were negatively correlated with the sperm motility (r = -0.229, P =.0220)
      and positively correlated with the total protein concentration (r = 0.793, P
      <.0001). This result supports that SPMI, one of the fragments of Sg, has its
      inhibitory effect on ejaculated spermatozoa in liquefied semen under
      physiological conditions.

PMID- 14581515
TI  - Effect of simulated microgravity on testosterone and sperm motility in mice.
AB  - We examined changes in the serum testosterone level and in sperm in the testis
      and epididymis by using tail-suspended mice, which are a simulation model of the
      body fluid shift in space, to evaluate the possibility of spermatogenesis failure
      in space environment. We also studied pathological disorders of the testis in the
      tail-suspended mice. Tail suspension was imposed with a tail harness to a degree
      at which the hindlegs of mice did not touch the floor of the housing unit. In
      control mice, the tail was similarly fixed with a tail harness to impose the same
      stress, except that a hindleg remained on the floor. Body weight was not
      significantly different between the 2 groups during 7 days, and testicular weight
      was significantly different. The testosterone level was significantly lower in
      the tail-suspended group (0.71 +/- 1.24 ng/mL) than in the control group (2.38 +/
      3.50 ng/mL; P <.05). Microscopy with hematoxylin and eosin (HE) and periodic
      acid-Schiff (PAS) staining showed a small proportion of seminiferous tubules with
      impairment of spermatogenic function in the tail-suspended group, and
      multinucleated giant cells were occasionally noted. Terminal deoxynucleotidyl
      tranferase-mediated nick end-labeling staining revealed positive cells even in
      animals in which impairment was considered to be mild based on HE and PAS
      staining. Many cells showed intense p53 immunostaining compared to the control
      group, with more intense staining of the nucleus in the tail-suspended group. The
      proportion of motile sperm was slightly but not significantly reduced in the tail
      suspended group. However, the mean movement velocity of the motile spermatozoa
      was significantly decreased.

PMID- 14581516
TI  - Expression and localization of total Akt1 and phosphorylated Akt1 in the rat
      seminiferous epithelium.
AB  - Akt1 is a survival factor that is believed to play a role in the transcriptional
      modulation of a subset of genes associated with cell growth, proliferation, and
      apoptosis. We have explored in detail the expression of total Akt1 and
      phosphorylated Akt1 in the developing and adult rat testis. Throughout testis
      postnatal development, the expression of total Akt1 protein exhibited a mainly
      cytoplasmic localization within both the germ cells and the supporting Sertoli
      cells. In contrast, phosphorylated Akt1 staining demonstrated a mainly nuclear
      localization within germ cells. In the developmental sequence of germ cells,
      phosphorylated Akt1 stained the nuclei of spermatogonia, spermatocytes, and round
      spermatids. During spermiogenesis, phosphorylated Akt1 staining decreased in the
      nucleus and became localized to a bright spot at the base of the nucleus in
      elongate spermatids. Of interest, total Akt1 was found to localize to the
      perinuclear region of germ cells and the supranuclear region of Sertoli cells,
      depending on fixation. Further analysis demonstrated this staining to be
      associated with the Golgi complex in both germ and Sertoli cells.

PMID- 14581517
TI  - Identification of differentially expressed genes in mouse spermatogenesis.
AB  - Complementary DNA microarray and quantitative polymerase chain reaction were used
      as tools for discovering genes that are differentially expressed in the mouse
      under normal physiological conditions at distinctive stages of male germ cell
      development, that is, type A spermatogonia, pachytene spermatocytes, and round
      spermatids. By using this strategy, we identified a set of genes exhibiting
      differential expression patterns in spermatogenesis, suggesting that specific
      functions of the encoded products occurred during the developmental process.
      Among them were several genes previously not known to be active in testis, which
      signified undiscovered functional roles of these genes during spermatogenesis.
      Many of the genes identified were not previously characterized. This study
      highlights new targets for manipulation to unravel the molecular mechanism of
      spermatogenesis.

PMID- 14581519
TI  - Abundance of repetitive sequence elements in the mouse testis-specific lactate
      dehydrogenase-C gene.
AB  - We have cloned and sequenced the entire mouse ldhc gene and mapped it physically
      in relation to the somatic ldha gene. The 2 genes were found to be oriented in
      head-to-tail fashion with about a 6-kilobase (kb) distance between the 3' end of
      ldha and the 5' end of ldhc. The ldhc gene is composed of 43% repetitive elements
      compared to only 16% in the ldha gene. Despite the close physical distance of
      mouse ldha and ldhc, the 2 genes have a very different content of repetitive
      elements, and this most likely reflects different levels of selective pressure.

PMID- 14581520
TI  - Penile venous anatomy: an additional description and its clinical implication.
AB  - The human penile venous system has been well studied and described but the
      demonstration of extra venous channels in imaging films prompted us to seek
      refinement of our anatomical knowledge of this venous system. Cavernosography in
      37 patients who had venous stripping surgery and now suffered recurrent erectile
      dysfunction consistently showed an independent vein, smaller than the deep dorsal
      vein, running almost in the same position of the deep dorsal vein even though the
      latter had been removed unequivocally in previous surgery. Cavernosography in 9
      patients who underwent intraoperative films also demonstrated the presence of
      this cavernosal vein in addition to the deep dorsal vein. Meticulous dissection
      of the penis under the microscope was then performed in 21 male cadavers and we
      found a cavernosal vein coursing along each corpus cavernosum all the way
      distally to the glans and draining directly into the Santorini's plexus in 19
      subjects. This is in contrast to the previous description that this cavernosal
      vein was a short vein in the penile hilum. Two sets of para-arterial veins, which
      have not been reported in the literature, were found to accompany each dorsal
      artery in all 21 subjects. This more extensive and extra venous drainage might
      have important implication for venous stripping surgery in the treatment of
      erectile dysfunction.

PMID- 14581518
TI  - Chronic administration of atrial natriuretic peptide reduces testosterone
      production of testes in mice.
AB  - The purpose of the present study was to examine the effect of the long-term
      administration of human atrial natriuretic peptide (ANP) on testosterone
      production in male mice. Twenty-five mice received ANP (20 ng/hour/g body weight)
      for 7 days via mini-osmotic pump, and the other group (n = 25) received twice
      daily intraperitoneal injections. After death, levels of follicle-stimulating
      hormone, luteinizing hormone (LH), and testosterone in plasma, pituitary gland,
      and testis were measured by radioimmunoassay. Five mice from each group were
      examined histologically. In the minipump group, pituitary and plasma levels were
      significantly higher than those in the control group (771.2 +/- 43.6 vs 644.8 +/-
      24.9 ng/mg and 6.7 +/- 0.6 ng/mg vs 2.5 +/- 0.6 ng/mL, respectively). In the
      intraperitoneal group, plasma LH levels were significantly higher in the ANP
      treated group than that in control mice (9.6 +/- 0.3 ng/mg vs 3.8 +/- 0.5 ng/mL),
      whereas pituitary levels did not differ significantly. In both studies,
      testicular and plasma testosterone levels were significantly lower than those in
      control mice (P <.02). Histological features of the testes in ANP-treated mice
      revealed structural disorganization and inhibition of spermatogenesis. We
      conclude that the chronic administration of ANP may result in reduced
      testosterone production due to testicular damage.

PMID- 14581521
TI  - Synopsis: 2003 Annual Meeting of the American Society of Andrology.

PMID- 14581522
TI  - Fatty acid binding protein as a serum marker for the early diagnosis of stroke: a
      pilot study.
AB  - No biological marker is currently available for the routine diagnosis of stroke.
      The aim of this pilot study was to determine whether heart-fatty acid binding
      protein (H-FABP) could be used as a valid diagnostic biomarker for stroke, as
      compared with neuron-specific enolase (NSE) and S100B proteins. Using two
      dimensional gel electrophoresis separation of cerebrospinal fluid proteins and
      mass spectrometry techniques, FABP was found elevated in the cerebrospinal fluid
      of deceased patients, used as a model of massive brain damage. Because H-FABP, a
      FABP form present in many organs, is also localized in the brain, an enzyme
      linked immunosorbant assay was developed to detect H-FABP in stroke versus
      control plasma samples. However, H-FABP being also a marker of acute myocardial
      infarction (AMI), troponin-I and creatine kinase-MB levels were assayed at the
      same time in order to exclude any concomitant heart damage. NSE and S100B levels
      were assayed simultaneously. These assays were assessed in serial plasma samples
      from 22 control patients with no AMI or stroke, 20 patients with AMI but no
      stroke, and 22 patients with an acute stroke but no AMI. Twenty-two out of the 22
      control patients and 15 out of the 22 stroke patients were correctly classified,
      figures much better than those obtained with NSE or S100B, in the same study's
      population. H-FABP appears to be a valid serum biomarker for the early diagnosis
      of stroke. Further studies on large cohorts of patients are warranted.

PMID- 14581523
TI  - Antibody-mediated protection against cytotoxic T-cell escape in coronavirus
      induced demyelination.
AB  - C57BL/6 (B6) mice infected with mouse hepatitis virus (MHV) strain JHM develop a
      clinically evident, demyelinating encephalomyelitis. Infectious virus can be
      isolated from the spinal cords of these mice and is invariably mutated in the
      immunodominant CD8 T-cell epitope recognized in this strain. We showed previously
      that these persistently infected mice did not mount a measurable serum anti-MHV
      neutralizing antibody response. Here we show that cytotoxic T-lymphocyte (CTL)
      escape was not detected in MHV-infected BALB/b mice (H-2(b) haplotype), even
      though the same CD8 T-cell epitopes were recognized as in B6 mice. BALB/b mice
      had 25-fold more MHV-specific antibody-secreting cells in the central nervous
      system, the site of infection, than B6 mice, suggesting that local production of
      anti-MHV antibody contributed to this absence of CTL escape. Additionally,
      administration of anti-MHV neutralizing antibody to infected B6 mice suppressed
      the development of CTL escape mutants. These findings indicate a key role for the
      anti-MHV antibody response in suppressing virus replication, thereby minimizing
      the emergence and competitive advantage of CTL escape mutants.

PMID- 14581524
TI  - Hep3B human hepatoma cells support replication of the wild-type and a 5'-end
      deletion mutant GB virus B replicon.
AB  - Hepatitis C virus (HCV) and GB virus B (GBV-B) replicons have been reported to
      replicate only in Huh7 cells. Here we demonstrate that subpopulations of another
      human hepatoma cell line, Hep3B, are permissive for the GBV-B replicon, showing
      different levels of enhancement of replication from those of the unselected
      parental cell population. Adaptive mutations are not required for replication of
      the GBV-B replicon in these cells, as already demonstrated for Huh7 cells.
      Nonetheless, we identified a mutant replicon in one of the selected cell lines,
      which, although lacking the 5' end proximal stem-loop, is able to replicate in
      Hep3B cells as well as in Huh7 cells. This mutant indeed shows a higher
      replication efficiency than does wild-type replicon, especially in the Hep3B cell
      clone from which it was originally recovered. This indicates that the stem-loop
      Ia is not necessary for replication of the GBV-B replicon in human cells, unlike
      what occurs with HCV, and that its absence can even provide a selective
      advantage.

PMID- 14581525
TI  - PPPYVEPTAP motif is the late domain of human T-cell leukemia virus type 1 Gag and
      mediates its functional interaction with cellular proteins Nedd4 and Tsg101
      [corrected].
AB  - The human T-cell leukemia virus type 1 (HTLV-1) Gag polyprotein contains two
      adjacent proline-rich motifs (sequence PPPYVEPTAP) in the C terminus of the
      matrix domain [corrected]. Proline-to-alanine mutations were introduced into
      either or both motifs of HTLV-1 to determine the effect on the release of HTLV-1
      virus-like particles from 293T cells. The release of both single mutants was
      significantly reduced, whereas a double mutation in both motifs abolished the
      release of the HTLV-1 particles. Two-hybrid and in vitro binding assays showed
      that the HTLV-1 Gag polyprotein binds both Tsg101 and Nedd4 proteins. The
      interaction with HTLV-1 Gag required the central WW domain of Nedd4 and the
      ubiquitin enzyme variant (UEV) domain of Tsg101. We expressed various fragments
      of Nedd4 and Tsg101 proteins in 293T cells and tested for their ability to
      interfere with virion release mediated by the HTLV-1 Gag-Pro polyprotein.
      Fragments consisting of the N-terminal UEV domain of Tsg101 and the central WW
      and C-terminal Hect domains of Nedd4 protein all caused transdominant inhibition
      of HTLV-1 particle release. Similarly, inhibition of the proteasome significantly
      decreased HTLV-1 particle release. Furthermore, the WW domain overexpression
      caused an early arrest of HTLV-1 particle morphogenesis before the membrane is
      deformed into the typical half-shell structure. This result suggests that Nedd4
      is involved early in budding of HTLV-1.

PMID- 14581526
TI  - Atomic force microscopy investigation of human immunodeficiency virus (HIV) and
      HIV-infected lymphocytes.
AB  - Isolated human immunodeficiency virus (HIV) and HIV-infected human lymphocytes in
      culture have been imaged for the first time by atomic force microscopy (AFM).
      Purified virus particles spread on glass substrates are roughly spherical,
      reasonably uniform, though pleomorphic in appearance, and have diameters of about
      120 nm. Similar particles are also seen on infected cell surfaces, but
      morphologies and sizes are considerably more varied, possibly a reflection of the
      budding process. The surfaces of HIV particles exhibit "tufts" of protein,
      presumably gp120, which do not physically resemble spikes. The protein tufts,
      which number about 100 per particle, have average diameters of about 200 A, but
      with a large variance. They likely consist of arbitrary associations of small
      numbers of gp120 monomers on the surface. In examining several hundred virus
      particles, we found no evidence that the gp120 monomers form threefold symmetric
      trimers. Although >95% of HIV-infected H9 lymphocytic cells were producing HIV
      antigens by immunofluorescent assay, most lymphocytes displayed few or no virus
      on their surfaces, while others were almost covered by a hundred or more viruses,
      suggesting a dependence on cell cycle or physiology. HIV-infected cells treated
      with a viral protease inhibitor and their progeny viruses were also imaged by AFM
      and were indistinguishable from untreated virions. Isolated HIV virions were
      disrupted by exposure to mild neutral detergents (Tween 20 and CHAPS) at
      concentrations from 0.25 to 2.0%. Among the products observed were intact
      virions, the remnants of completely degraded virions, and partially disrupted
      particles that lacked sectors of surface proteins as well as virions that were
      split or broken open to reveal their empty interiors. Capsids containing nucleic
      acid were not seen, suggesting that the capsids were even more fragile than the
      envelope and were totally degraded and lost. From these images, a good estimate
      of the thickness of the envelope protein-membrane-matrix protein outer shell of
      the virion was obtained. Treatment with even low concentrations (<0.1%) of sodium
      dodecyl sulfate completely destroyed all virions but produced many interesting
      products, including aggregates of viral proteins with strands of nucleic acid.

PMID- 14581527
TI  - Resistance of human hepatitis delta virus RNAs to dicer activity.
AB  - The endonuclease dicer cleaves RNAs that are 100% double stranded and certain
      RNAs with extensive but <100% pairing to release approximately 21-nucleotide (nt)
      fragments. Circular 1,679-nt genomic and antigenomic RNAs of human hepatitis
      delta virus (HDV) can fold into a rod-like structure with 74% pairing. However,
      during HDV replication in hepatocytes of human, woodchuck, and mouse origin, no
      approximately 21-nt RNAs were detected. Likewise, in vitro, purified recombinant
      dicer gave <0.2% cleavage of unit-length HDV RNAs. Similarly, rod-like RNAs of
      potato spindle tuber viroid (PSTVd) and avocado sunblotch viroid (ASBVd) were
      only 0.5% cleaved. Furthermore, when a 66-nt hairpin RNA with 79% pairing, the
      putative precursor to miR-122, which is an abundant liver micro-RNA, replaced one
      end of HDV genomic RNA, it was poorly cleaved, both in vivo and in vitro. In
      contrast, this 66-nt hairpin, in the absence of appended HDV sequences, was >80%
      cleaved in vitro. Other 66-nt hairpins derived from one end of genomic HDV,
      PSTVd, or ASBVd RNAs were also cleaved. Apparently, for unit-length RNAs of HDV,
      PSTVd, and ASBVd, it is the extended structure with <100% base pairing that
      confers significant resistance to dicer action.

PMID- 14581528
TI  - Low frequency of cytotoxic T lymphocytes against the novel HLA-A*0201-restricted
      JC virus epitope VP1(p36) in patients with proven or possible progressive
      multifocal leukoencephalopathy.
AB  - JC virus (JCV)-specific cytotoxic T lymphocytes (CTL) in peripheral blood are
      associated with a favorable outcome in patients with progressive multifocal
      leukoencephalopathy (PML). However, the frequency of these cells in the
      peripheral blood mononuclear cells (PBMC) of PML patients is unknown. To develop
      a highly sensitive assay for detecting the cellular immune response against this
      virus, we performed a CTL epitope mapping study of JCV VP1 major capsid protein
      by using overlapping peptides. A novel HLA-A*0201-restricted epitope, the
      VP1(p36) peptide SITEVECFL, was characterized. The cellular immune response
      against JCV was assessed in 32 study subjects. By combining the results of the
      (51)Cr release assay on pooled peptides and staining with the HLA-A*0201/JCV
      VP1(p36) tetramer, VP1-specific CTL were detected in 10 of 11 PML survivors (91%)
      versus only 1 of 11 PML progressors (9%, P = 0.0003). VP1-specific CTL were also
      detected in two of two patients recently diagnosed with PML and in four of four
      human immunodeficiency virus-positive patients with possible PML. The frequency
      of CTL specific for the novel VP1(p36) and the previously described VP1(p100)
      epitopes was determined. In two patients, the frequency of CTL specific for the
      VP1(p36) or VP1(p100) epitopes, as determined by fresh blood tetramer staining
      (FBTS), ranged from 1/6,000 to 1/24,000 PBMC. A CTL sorting technique combining
      tetramer staining and selection with immunomagnetic beads allowed the detection
      of epitope-specific CTL in two cases that were determined to be negative by FBTS.
      The phenotype of these CTL in vivo was consistent with activated memory cells.
      These data suggest that, although present in low numbers, JCV-specific CTL may be
      of central importance in the containment of JCV spread in immunosuppressed
      individuals.

PMID- 14581530
TI  - The alkylated imino sugar, n-(n-Nonyl)-deoxygalactonojirimycin, reduces the
      amount of hepatitis B virus nucleocapsid in tissue culture.
AB  - n-(n-Nonyl)-deoxygalactonojirimycin (n,n-DGJ), an alkylated imino sugar, reduces
      the amount of HBV DNA produced within the stably transfected HBV-producing
      HepG2.2.15 line in culture and is under consideration for development as a human
      therapeutic. n,n-DGJ does not appear to inhibit HBV DNA polymerase activity or
      envelop antigen production (A. Mehta, S. Carrouee, B. Conyers, R. Jordan, T.
      Butters, R. A. Dwek, and T. M. Block, Hepatology 33:1488-1495, 2001), and the
      mechanism of antiviral action is unknown. In this study, the step in the virus
      life cycle affected by n,n-DGJ was explored. Using Northern analysis and
      immunoprecipitation with anti-HBc antibody, we found that, under conditions in
      which cell viability was not affected but viral DNA production was substantially
      reduced, neither the amount of HBV transcription products nor the core
      polypeptide was detectably reduced. However, the pregenomic RNA, endogenous
      polymerase activity, and core polypeptide sedimenting in sucrose gradients with a
      density consistent with that of assembled nucleocapsids were significantly less
      in the HepG2.2.15 cells incubated with n,n-DGJ. These data suggest that n,n-DGJ
      either prevents the maturation of HBV nucleocapsids or destabilizes the formed
      nucleocapsids. Although the cellular and viral mediators of this inhibition are
      not known, depletion of nucleocapsid has been attributed to some other compounds
      as well as interferon's mechanism of anti-HBV action. The similarities and
      differences between this alkylated imino sugar and these other mediators are
      discussed.

PMID- 14581529
TI  - Oct-1 is posttranslationally modified and exhibits reduced capacity to bind
      cognate sites at late times after infection with herpes simplex virus 1.
AB  - In herpes simplex virus 1-infected cells, a high level of alpha gene expression
      requires the transactivation of the genes by a complex containing the viral alpha
      transinducing factor (alphaTIF) and two cellular proteins. The latter two, HCF-1
      and octamer binding protein Oct-1, are transcriptional factors regulated in a
      cell cycle-dependent manner. alphaTIF is a protein made late in infection but
      packaged with the virion to transactivate viral genes in newly infected cells. In
      light of the accumulation of large amounts of alphaTIF, the absence of alpha gene
      expression late in infection suggested the possibility that one or more
      transcriptional factors required for alpha gene expression is modified late in
      infection. Here we report that Oct-1 is posttranscriptionally modified late in
      infection, that the modification is mediated by the virus but does not involve
      viral protein kinases or cdc2 kinase activated by the virus late in infection,
      and that the modified Oct-1 has a reduced affinity for its cognate DNA site.
      These results are consistent with the hypothesis that modification of Oct-1
      transcriptional factor could account at least in part for the shutoff of alpha
      gene expression late in infection.

PMID- 14581531
TI  - Construction, rescue, and characterization of vectors derived from ovine
      atadenovirus.
AB  - Gene transfer vectors derived from ovine atadenovirus type 7 (OAdV) can
      efficiently infect a variety of mammalian cells in vitro and in vivo to deliver
      and express transgenes. However, early OAdV vectors were designed on human
      mastadenovirus principles prior to the complete characterization of OAdV genes
      and transcripts. The distinctive arrangement of the OAdV genome has suggested
      ways to improve OAdV vector design and utility. We therefore developed a cosmid
      based approach that allows efficient construction of recombinant ovine
      atadenovirus genomes in which the transgene is inserted at one of three sites.
      Viruses were rescued by transfection of viral DNA into a new ovine fetal skin
      fibroblast producer cell line, HVO156. The suitability of the three insertion
      sites was compared with respect to virus rescue efficiency, gene expression
      levels, and genetic stability of the vectors. We found that one vector with a
      transgene inserted at site 1, between the pVIII and fiber genes, was unstable.
      Only one vector that carried a transgene at site 2, near the right end of the
      genome, together with a nearby deletion was rescued. In contrast, several vectors
      with different transgenes inserted in site 3, between the E4 and RH transcription
      units, were repeatedly rescued, and these vectors were stable over at least four
      passages. Transgene orientation in site 3 had only little effect on expression.
      Finally, a vector carrying a human factor IX cDNA at site 3, when administered
      intravenously, produced nearly physiological levels of human factor IX in mice.
      The availability of an efficient method for vector construction and the
      identification of a new insertion site for virus rescue and gene expression
      substantially enhance the utility of the OAdV vector system.

PMID- 14581532
TI  - Induction of caspase-dependent apoptosis in cultured rat oligodendrocytes by
      murine coronavirus is mediated during cell entry and does not require virus
      replication.
AB  - Murine coronavirus mouse hepatitis virus (MHV) causes demyelination of the
      central nervous system (CNS) in rats and mice. Apoptotic oligodendrocytes have
      been detected in the vicinity of the CNS demyelinating lesions in these animals.
      However, whether MHV can directly induce oligodendrocyte apoptosis has not been
      documented. Here, we established a rat oligodendrocyte culture that is
      morphologically and phenotypically indistinguishable from the primary rat
      oligodendrocytes. Using this culture, we showed that mature rat oligodendrocytes
      were permissive to MHV infection but did not support productive virus
      replication. Significantly, oligodendrocytes infected with both live and
      ultraviolet light-inactivated viruses underwent apoptosis to a similar extent,
      which was readily detectable at 24 h postinfection as revealed by apoptotic
      bodies and DNA fragmentation, indicating that MHV-induced apoptosis is mediated
      during the early stages of the virus life cycle and does not require virus
      replication. Prior treatment of cells with the lysosomotropic agents NH(4)Cl and
      chloroquine as well as the vacuolar proton pump-ATPase inhibitor bafilomycin A1,
      all of which block the acidification of the endosome, prevented oligodendrocytes
      from succumbing to apoptosis induced by MHV mutant OBLV60, which enters cells via
      endocytosis, indicating that fusion between the viral envelope and cell membranes
      triggers the apoptotic cascade. Treatment with the pan-caspase inhibitor Z-VAD
      fmk blocked MHV-induced apoptosis, suggesting an involvement of the caspase
      dependent pathway. Our results, thus, for the first time provide unequivocal
      evidence that infection of oligodendrocytes with MHV directly results in
      apoptosis. This finding provides an explanation for the destruction of
      oligodendrocytes and the damage of myelin sheath in MHV-infected CNS and suggests
      that oligodendrocyte apoptosis may be one of the underlying mechanisms for the
      pathogenesis of MHV-induced demyelinating diseases in animals.

PMID- 14581533
TI  - Inhibition of human immunodeficiency virus type 1 replication in primary
      macrophages by using Tat- or CCR5-specific small interfering RNAs expressed from
      a lentivirus vector.
AB  - Although several groups have demonstrated that RNA interference, induced by
      transfection of small interfering RNA (siRNA) duplexes, can protect cells against
      a viral challenge in culture, this protection is transient. Here, we describe
      lentivirus expression vectors that can stably express siRNAs at levels sufficient
      to block virus replication. We have used these vectors to stably express siRNAs
      specific for the essential human immunodeficiency virus type 1 (HIV-1) Tat
      transcription factor or specific for a cellular coreceptor, CCR5, that is
      required for infection by the majority of primary HIV-1 isolates. These
      lentivirus vectors are shown to protect cells, including primary macrophages,
      against HIV-1 infection in culture by inducing selective degradation of their
      target mRNA species. These data suggest that it should be possible to block the
      expression of specific viral or cellular genes in vivo by using viral vectors to
      stably express the appropriate siRNAs.

PMID- 14581534
TI  - Primary sequence and secondary structure motifs in spleen necrosis virus RU5
      confer translational utilization of unspliced human immunodeficiency virus type 1
      reporter RNA.
AB  - The 5' long terminal repeat (LTR) of spleen necrosis virus (SNV) contains a
      unique posttranscriptional control element that facilitates Rev/Rev-responsive
      element-independent expression of unspliced human immunodeficiency virus type 1
      (HIV-1) gag reporter RNA. HIV-1 Gag expression is eliminated when SNV LTR is
      repositioned to the 3' untranslated region or when the RU5 region is positioned
      in the antisense orientation. RU5 corresponds to the 5' RNA terminus, and results
      presented here indicate that Gag production is sustained upon introduction of
      transcribed spacers that reposition SNV RU5 35 to 200 nucleotides downstream.
      Concordant results of deletion and point mutagenesis identified two functionally
      redundant and synergistic motifs (designated A and C) that are necessary and
      sufficient for SNV RU5 activity. Enzymatic analysis of SNV RU5 RNA structure
      determined that A and C correspond to stem-loop structures. Quantitative RNA and
      protein analysis of A and C mutants revealed that the structural integrity of A
      and C is necessary for protein production, and loss of function correlates with
      little change in steady-state level, splicing efficiency, or cytoplasmic
      accumulation of HIV-1 gag reporter RNA. Instead, the structural mutations
      eliminate cytoplasmic utilization as an mRNA template for Gag protein production.
      Point mutations of unpaired loop-and-bulge nucleotides that maintain the
      structure of A eliminate activity. The results show that the unpaired UUGU loop
      and U-rich bulges function together and are candidate SNV RU5 binding sites for
      the host cell protein(s) that directs cytoplasmic utilization of unspliced HIV-1
      reporter RNA.

PMID- 14581535
TI  - Receptor priming of major group human rhinoviruses for uncoating and entry at
      mild low-pH environments.
AB  - Receptor priming of low-pH-triggered virus entry has been described for an
      enveloped virus (15). Here we show with major group human rhinoviruses (HRV) and
      its intercellular adhesion molecule-1 receptor that nonenveloped viruses follow
      this novel cell entry principle. In vitro the receptor primed HRV for efficient
      uncoating at mild low pH (5.5 to 6.0). Agents preventing endosomal acidification
      reduced or blocked rhinovirus cell infection, while nocodazole had no effect on
      infection of any serotype tested. The entry inhibitory effect of lysosomotropic
      agents was overcome by exposing cell-internalized HRV to mild low pH (5.5 to
      6.0). We therefore conclude that receptor priming of major group HRV must occur
      in vivo as well. Cooperation of a cellular receptor and low pH in virus uncoating
      will polarize the exit of the genome to the receptor-bound, membrane-proximal
      region of the virus particle during acidification of endosomes. This process must
      be required for efficient penetration of the cellular membrane by viruses.

PMID- 14581536
TI  - Telomere repeat binding factors TRF1, TRF2, and hRAP1 modulate replication of
      Epstein-Barr virus OriP.
AB  - Epstein-Barr virus OriP confers cell cycle-dependent DNA replication and stable
      maintenance on plasmids in EBNA1-positive cells. The dyad symmetry region of OriP
      contains four EBNA1 binding sites that are punctuated by 9-bp repeats referred to
      as nonamers. Previous work has shown that the nonamers bind to cellular factors
      associated with human telomeres and contribute to episomal maintenance of OriP.
      In this work, we show that substitution mutation of all three nonamer sites
      reduces both DNA replication and plasmid maintenance of OriP-containing plasmids
      by 2.5- to 5-fold. The nonamers were required for high-affinity binding of TRF1,
      TRF2, and hRap1 to the dyad symmetry element but were not essential for the
      binding of EBNA1 as determined by DNA affinity purification from nuclear
      extracts. Chromatin immunoprecipitation assays indicated that TRF1, TRF2, and
      hRap1 bound OriP in vivo. Cell cycle studies indicate that TRF2 binding to OriP
      peaks in G(1)/S while TRF1 binding peaks in G(2)/M. OriP replication was
      inhibited by transfection of full-length TRF1 but not by deletion mutants lacking
      the myb DNA binding domain. In contrast, OriP replication was not affected by
      transfection of full-length TRF2 or hRap1 but was potently inhibited by dominant
      negative TRF2 or hRap1 amino-terminal truncation mutants. Knockdown experiments
      with short interfering RNAs (siRNAs) directed against TRF2 and hRap1 severely
      reduced OriP replication, while TRF1 siRNA had a modest stimulatory effect on
      OriP replication. These results indicate that TRF2 and hRap1 promote, while TRF1
      antagonizes, OriP-dependent DNA replication and suggest that these telomeric
      factors contribute to the establishment of replication competence at OriP.

PMID- 14581537
TI  - Conditional rather than absolute requirements of the capsid coding sequence for
      initiation of methionine-independent translation in Plautia stali intestine
      virus.
AB  - The positive-stranded RNA genome of Plautia stali intestine virus (PSIV) has an
      internal ribosome entry site (IRES) in an intergenic region (IGR). The IGR-IRES
      of PSIV initiates translation of the capsid protein by using CAA, the codon for
      glutamine. It was previously reported (J. Sasaki and N. Nakashima, J. Virol.
      73:1219-1226, 1999) that IGR-IRES extended by several nucleotides into the capsid
      open reading frame (ORF). Despite the fact that the secondary structure model of
      the IGR-IRES is highly conserved, we were unable to find structural similarities
      in the 5' region of the capsid ORFs in related viruses. Therefore, we reevaluated
      the role of the capsid ORF in IGR-IRES-mediated translation in PSIV. Mutation of
      the CAA codon with various triplets did not inhibit IGR-IRES-mediated
      translation. N-terminal amino acid analyses of mutated products showed that the
      IGR-IRES could initiate translation by using various elongator tRNAs. By
      replacement of the capsid ORF with exogenous coding sequences having AUG deleted,
      translation products were produced in most cases, but capsid-exogenous fusion
      proteins were produced more efficiently than were the translation products. These
      data indicate that the 5' part of the capsid ORF is not an absolute requirement
      for the IGR-IRES-mediated translation. RNA structure probing analyses showed that
      the 5' part of the capsid ORF was a single strand, while that of exogenous
      reading frames was structured. Exogenous sequences also caused structural
      distortion in the 3' part of the IGR-IRES. We hypothesize that the single
      stranded capsid ORF helps to form the tertiary structure of the IGR-IRES and
      facilitates precise positioning of ribosomes.

PMID- 14581538
TI  - G541R within the 4070A TM protein regulates fusion in murine leukemia viruses.
AB  - The mutation G541R within the ectodomain of TM was isolated in three independent
      chimeric enveloped murine leukemia virus (MuLV) viral populations originally
      impaired in viral passage and in wild-type 4070A. Isolation of G541R in multiple
      populations suggested it played a critical role in viral envelope function. Using
      a viral vector system, the observed effects of the G541R mutation within MuLV
      envelope proteins were pleiotropic and included effects on the regulation of SU
      TM interactions and membrane fusion. G541R suppresses enhanced cell-cell fusion
      events attributable to the absence of the R-peptide yet does not adversely affect
      virus titers. The ability to suppress cell-cell fusion is dependent on the
      presence of the C terminus of the amphotropic 4070A SU protein. Within the wild
      type 4070A envelope background, the mutation results in a decreased level of Env
      at the cell surface that is mirrored in the virion. The TM mutation alters
      recognition of the SU C terminus by a monoclonal antibody, suggestive of an
      altered conformation. The presence of G541R allowed the virus to achieve a
      balance between cytopathogenicity and replication and restored productive viral
      entry.

PMID- 14581539
TI  - DC-SIGN and L-SIGN can act as attachment receptors for alphaviruses and
      distinguish between mosquito cell- and mammalian cell-derived viruses.
AB  - C-type lectins such as DC-SIGN and L-SIGN, which bind mannose-enriched
      carbohydrate modifications of host and pathogen proteins, have been shown to bind
      glycoproteins of several viruses and facilitate either cis or trans infection. DC
      SIGN and L-SIGN are expressed in several early targets of arbovirus infection,
      including dendritic cells (DCs) and cells of the reticuloendothelial system. In
      the present study, we show that DC-SIGN and L-SIGN can function as attachment
      receptors for Sindbis (SB) virus, an arbovirus of the Alphavirus genus. Human
      monocytic THP-1 cells stably transfected with DC-SIGN or L-SIGN were permissive
      for SB virus replication, while untransfected controls were essentially
      nonpermissive. The majority of control THP-1 cells were permissive when
      attachment and entry steps were eliminated through electroporation of virus
      transcripts. Infectivity for the DC-SIGN/L-SIGN-expressing cells was largely
      blocked by yeast mannan, EDTA, or a DC-SIGN/L-SIGN-specific monoclonal antibody.
      Infection of primary human DCs by SB virus was also dependent upon SIGN
      expression by similar criteria. Furthermore, production of virus particles in
      either C6/36 mosquito cells or CHO mammalian cells under conditions that limited
      complex carbohydrate content greatly increased SB virus binding to and infection
      of THP-1 cells expressing these lectins. C6/36-derived virus also was much more
      infectious for primary human DCs than CHO-derived virus. These results suggest
      that (i) lectin molecules such as DC-SIGN and L-SIGN may represent common
      attachment receptor molecules for arthropod-borne viruses, (ii) arbovirus
      particles produced in and delivered by arthropod vectors may preferentially
      target vertebrate host cells bearing these or similar lectin molecules, and (iii)
      a cell line has been identified that can productively replicate alphaviruses but
      is deficient in attachment receptors.

PMID- 14581540
TI  - Mechanism of RNA recombination in carmo- and tombusviruses: evidence for template
      switching by the RNA-dependent RNA polymerase in vitro.
AB  - RNA recombination occurs frequently during replication of tombusviruses and
      carmoviruses, which are related small plus-sense RNA viruses of plants. The most
      common recombinants generated by these viruses are either defective interfering
      (DI) RNAs or chimeric satellite RNAs, which are thought to be generated by
      template switching of the viral RNA-dependent RNA polymerase (RdRp) during the
      viral replication process. To test if RNA recombination is mediated by the viral
      RdRp, we used either a purified recombinant RdRp of Turnip crinkle carmovirus or
      a partially purified RdRp preparation of Cucumber necrosis tombusvirus. We
      demonstrated that these RdRp preparations generated RNA recombinants in vitro.
      The RdRp-driven template switching events occurred between either identical
      templates or two different RNA templates. The template containing a replication
      enhancer recombined more efficiently than templates containing artificial
      sequences. We also observed that AU-rich sequences promote recombination more
      efficiently than GC-rich sequences. Cloning and sequencing of the generated
      recombinants revealed that the junction sites were located frequently at the ends
      of the templates (end-to-end template switching). We also found several
      recombinants that were generated by template switching involving internal
      positions in the RNA templates. In contrast, RNA ligation-based RNA recombination
      was not detected in vitro. Demonstration of the ability of carmo- and tombusvirus
      RdRps to switch RNA templates in vitro supports the copy-choice models of RNA
      recombination and DI RNA formation for these viruses.

PMID- 14581541
TI  - Hepatitis delta virus RNA encoding the large delta antigen cannot sustain
      replication due to rapid accumulation of mutations associated with RNA editing.
AB  - Hepatitis delta virus (HDV) contains two RNA species (HDV-S and HDV-L), which
      encode the small and large forms of hepatitis delta antigens (S- and L-HDAg),
      respectively. HDV-L RNA is a result of an RNA editing event occurring at an
      amber/W site of HDV-S RNA. RNA editing must be regulated to prevent premature and
      excessive accumulation of HDV-L RNA in the viral life cycle. In this study, we
      used an RNA transfection procedure to study the replication abilities of HDV-L
      and HDV-S RNA. While HDV-S led to robust RNA replication, HDV-L could not
      replicate even after 6 days following transfection. The failure of HDV-L to
      replicate was not due to insufficient amounts of S-HDAg, as identical results
      were obtained in a cell line that stably overexpresses S-HDAg. Also, it was not
      due to possible inhibition by L-HDAg, as HDV-S RNA replication was not affected
      when both HDV-L and HDV-S RNA were cotransfected. Further, when L-HDAg expression
      from HDV-L RNA was abolished by site-directed mutagenesis, the mutant HDV-L RNA
      also failed to replicate. Unexpectedly, when the kinetics of RNA replication was
      examined daily, HDV-L was found to replicate at a low level at the early time
      points (1 to 2 days posttransfection) but then lose this capability at later time
      points. Sequence analysis of the replicated HDV-L RNA at day 1 posttransfection
      showed that it had undergone multiple nucleotide changes, particularly in the
      region near the putative promoter region of HDV RNA replication. In contrast,
      very few mutations were found in HDV-S RNA. These results suggest that the
      editing at the amber/W site triggers a series of additional mutations which
      rapidly reduce the replication efficiency of the resultant HDV genome and thus
      help regulate the amount of HDV-L RNA in infected cells. They also explain why L
      HDAg is not produced early in HDV infection, despite the fact that HDV-L RNA is
      present in the virion.

PMID- 14581542
TI  - Contrasting use of CCR5 structural determinants by R5 and R5X4 variants within a
      human immunodeficiency virus type 1 primary isolate quasispecies.
AB  - Macrophagetropic R5 human immunodeficiency virus type 1 (HIV-1) isolates often
      evolve into dualtropic R5X4 variants during disease progression. The structural
      basis for CCR5 coreceptor function has been studied in a limited number of
      prototype strains and suggests that R5 and R5X4 Envs interact differently with
      CCR5. However, differences between unrelated viruses may reflect strain-specific
      factors and do not necessarily represent changes resulting from R5 to R5X4
      evolution of a virus in vivo. Here we addressed CCR5 domains involved in fusion
      for a large set of closely related yet functionally distinct variants within a
      primary isolate swarm, employing R5 and R5X4 Envs derived from the HIV-1 89.6(PI)
      quasispecies. R5 variants of 89.6(PI) could fuse using either N-terminal or
      extracellular loop CCR5 sequences in the context of CCR5/CXCR2 chimeras, similar
      to the unrelated R5 strain JRFL, but R5X4 variants of 89.6(PI) were highly
      dependent on the CCR5 N terminus. Similarly, R5 89.6(PI) variants and isolate
      JRFL tolerated N-terminal CCR5 deletions, but fusion by most R5X4 variants was
      markedly impaired. R5 89.6(PI) Envs also tolerated multiple extracellular domain
      substitutions, while R5X4 variants did not. In contrast to CCR5 use, fusion by
      R5X4 variants of 89.6(PI) was largely independent of the CXCR4 N-terminal region.
      Thus, R5 and R5X4 species from a single swarm differ in how they interact with
      CCR5. These results suggest that R5 Envs possess a highly plastic capacity to
      interact with multiple CCR5 regions and support the concept that viral evolution
      in vivo results from the emergence of R5X4 variants with the capacity to use the
      CXCR4 extracellular loops but demonstrate less-flexible interactions with CCR5
      that are strongly dependent on the N-terminal region.

PMID- 14581543
TI  - Vaccine-induced immunopathology during bovine respiratory syncytial virus
      infection: exploring the parameters of pathogenesis.
AB  - The bovine and human respiratory syncytial viruses cause severe lower respiratory
      tract infections. Effective vaccines against the respiratory syncytial viruses
      have been lacking since vaccine failures in the 1960s and 1970s. In this report,
      we describe a bovine respiratory syncytial virus (bRSV) challenge model in which
      both classical bRSV respiratory infection and vaccine-enhanced immune pathology
      were reproduced. The classical, formalin-inactivated (FI) bRSV vaccine that has
      been associated with vaccine failure was efficient in inducing high antibody
      titers and reducing viral loads but also primed calves for a far more serious
      enhanced respiratory disease after a bRSV challenge, thereby mimicking the
      enhanced clinical situation in FI human RSV (hRSV)-immunized and hRSV-infected
      infants in the 1960s. We show that immunization with FI-bRSV mainly primes a Th2
      like inflammatory response that is characterized by a significant eosinophilic
      influx in the bronchial alveolar lung fluid and lung tissues and high levels of
      immunoglobulin E serum antibodies. The current model may be useful in the
      evaluation of new bRSV candidate vaccines for potency and safety.

PMID- 14581544
TI  - Dissociation of rabies virus matrix protein functions in regulation of viral RNA
      synthesis and virus assembly.
AB  - Recently, we have shown that the rabies virus (RV) matrix (M) protein regulates
      the balance of virus RNA synthesis by shifting synthesis activity from
      transcription to replication (S. Finke, R. Mueller-Waldeck, and K. K. Conzelmann,
      J. Gen. Virol. 84:1613-1621, 2003). Here we describe the identification of an M
      residue critical for regulation of RV RNA synthesis. By analyzing the phenotype
      of heterotypic RV M proteins with respect to RNA synthesis of RV SAD L16, we
      identified the M proteins of the RV ERA and PV strains as deficient. Comparison
      of M sequences suggested that a single residue, arginine 58, was critical. A
      recombinant virus having this amino acid exchanged with a glycine, SAD M(R58G),
      has lost the abilities to downregulate RV transcription and to stimulate
      replication. This resulted in an increase in the transcription rate of more than
      15-fold, as previously observed for M deletion mutants. Most importantly, the
      efficiencies of virus assembly and budding were equal for wild-type M and
      M(R58G), as determined in assays studying the transient complementation of an M-
      and G-deficient RV construct, NPgrL. In addition, virus particle density, protein
      composition, and specific infectivity of SAD L16 and SAD M(R58G) viruses were
      identical. Thus, we have identified mutations that affect the function of M only
      in regulation of RNA synthesis, but not in assembly and budding, providing
      evidence that these functions are genetically separable.

PMID- 14581545
TI  - Comprehensive analysis of class I and class II HLA antigens and chronic hepatitis
      B virus infection.
AB  - Following an acute hepatitis B virus (HBV) infection, clearance or persistence is
      determined in part by the vigor and breadth of the host immune response. Since
      the human leukocyte antigen system (HLA) is an integral component of the immune
      response, we hypothesized that the highly polymorphic HLA genes are key
      determinants of viral clearance. HLA class I and II genes were molecularly typed
      in 194 Caucasian individuals with viral persistence and 342 matched controls who
      had cleared the virus. A single class I allele, A*0301 (odds ratio [OR], 0.47;
      95% confidence interval [CI], 0.30 to 0.72; P = 0.0005) was associated with viral
      clearance. The class II allele DRB1*1302 was also associated with clearance (OR,
      0.42; 95% CI, 0.19 to 0.93; P = 0.03), but its significance decreased in a
      multivariate model that included other alleles associated with disease outcome as
      covariates. B*08 was associated with viral persistence both independently (OR,
      1.59; 95% CI, 1.04 to 2.43; P = 0.03) and as part of the conserved Caucasian
      haplotype A*01-B*08-DRB1*03. The B*44-Cw*1601 (OR, 2.23; 95% CI, 1.13 to 4.42; P
      = 0.02) and B*44-Cw*0501 (OR, 1.99; 95% CI, 1.22 to 3.24; P = 0.006) haplotypes
      were also associated with viral persistence. Interestingly, both the B*08
      haplotype and DR7, which forms a haplotype with B*44-Cw*1601, have been
      associated with nonresponse to the HBV vaccine. The associations with class I
      alleles are consistent with a previously implicated role for CD8-mediated
      cytolytic-T-cell response in determining the outcome of an acute HBV infection.

PMID- 14581546
TI  - Cytolytic CD4(+)-T-cell clones reactive to EBNA1 inhibit Epstein-Barr virus
      induced B-cell proliferation.
AB  - In the absence of immune surveillance, Epstein-Barr virus (EBV)-infected B cells
      generate neoplasms in vivo and transformed cell lines in vitro. In an in vitro
      system which modeled the first steps of in vivo immune control over
      posttransplant lymphoproliferative disease and lymphomas, our investigators
      previously demonstrated that memory CD4(+) T cells reactive to EBV were necessary
      and sufficient to prevent proliferation of B cells newly infected by EBV (S.
      Nikiforow et al., J. Virol. 75:3740-3752, 2001). Here, we show that three CD4(+)
      T-cell clones reactive to the latent EBV antigen EBNA1 also prevent the
      proliferation of newly infected B cells from major histocompatibility complex
      (MHC) class II-matched donors, a crucial first step in the transformation
      process. EBNA1-reactive T-cell clones recognized B cells as early as 4 days after
      EBV infection through an HLA-DR-restricted interaction. They secreted Th1-type
      and Th2-type cytokines and lysed EBV-transformed established lymphoblastoid cell
      lines via a Fas/Fas ligand-dependent mechanism. Once specifically activated, they
      also caused bystander regression and bystander killing of non-MHC-matched EBV
      infected B cells. Since EBNA1 is recognized by CD4(+) T cells from nearly all EBV
      seropositive individuals and evades detection by CD8(+) T cells, EBNA1-reactive
      CD4(+) T cells may control de novo expansion of B cells following EBV infection
      in vivo. Thus, EBNA1-reactive CD4(+)-T-cell clones may find use as adoptive
      immunotherapy against EBV-related lymphoproliferative disease and many other EBV
      associated tumors.

PMID- 14581547
TI  - Relationship between in vitro human immunodeficiency virus type 1 replication
      rate and virus load in plasma.
AB  - Although plasma human immunodeficiency virus type 1 (HIV-1) RNA concentration is
      a major determinant of the rate of HIV-1 disease progression, the reasons for
      variability in plasma virus loads among infected individuals are not fully
      understood. We conducted investigations with 15 HIV-1-infected individuals who
      were not receiving antiretroviral therapy to evaluate the hypothesis that HIV-1
      replication rate in vitro is a significant determinant of plasma virus load.
      Virus could not be isolated from one subject. Two subjects were excluded because
      they had features previously associated with distinct plasma virus loads and
      altered rates of disease progression; one harbored a syncytium-inducing virus and
      the second was heterozygous for a 32-bp deletion from the CCR5 gene. HIV-1
      replication rates were determined by culturing autologous virus isolates in
      phytohemagglutinin-treated peripheral blood mononuclear cells (PBMC) and
      determining the rate of p24 antigen production during the logarithmic phase of
      viral replication. The contribution of HIV-1 reverse transcriptase (RT) and
      protease (PR) alleles to replication capacity was assessed using recombinant
      viruses in a single-cycle infection assay. HIV-1 replication rates ranged from
      0.15 to 0.76 log(10) pg/ml/day and were reproducible within the same donor PBMC
      (coefficient of variation +/- 4%). RT-PR replication capacity ranged from 14 to
      95% of that of control virus and was linearly related to replication rate (r(2) =
      0.53; P = 0.007). Plasma HIV-1 RNA concentration was linearly related to
      replication rate (r(2) = 0.71; P < 0.001) and RT-PR replication capacity (r(2) =
      0.44; P = 0.019). These data suggest that different RT-PR alleles are important
      determinants of HIV-1 replication rates and that HIV-1 replication rate explains
      much of the variability in plasma virus load in chronic HIV-1 infection.

PMID- 14581548
TI  - Cap-independent translational enhancement by the 3' untranslated region of red
      clover necrotic mosaic virus RNA1.
AB  - Red clover necrotic mosaic virus (RCNMV) is a member of the genus Dianthovirus
      and has a bipartite positive-sense genomic RNA with 3' ends that are not
      polyadenylated. In this study, we show that both genomic RNA1 and RNA2 lack a 5'
      cap structure and that uncapped in vitro transcripts of RCNMV RNA1 replicated to
      a level comparable to that for capped transcripts in cowpea protoplasts. Because
      the 5' cap and 3' poly(A) tail play important roles in the translation of many
      eukaryotic mRNAs, genomic RNAs of RCNMV should contain an element(s) responsible
      for 5' cap- and poly(A) tail-independent translation of viral protein. By using a
      luciferase reporter assay system in vivo, we showed that the 3' untranslated
      region (UTR) of RNA1 alone significantly enhanced translation of the luciferase
      reporter gene in the absence of the 5' cap structure. Deletion studies revealed
      that the middle region (between nucleotides 3596 and 3732) in the 3' UTR,
      designated the 3' translation element of Dianthovirus RNA1 (3'TE-DR1), plays an
      important role in cap-independent translation. This region contained a stem-loop
      structure conserved among members of the genera Dianthovirus and LUTEOVIRUS: A
      five-base substitution in the loop abolished cap-independent translational
      activity, as reported for a luteovirus, indicating that this stem-loop is one of
      the functional structures in the 3'TE-DR1 involved in cap-independent
      translation. Finally, we suggest that cap-independent translational activity is
      required for RCNMV RNA1 replication in protoplasts.

PMID- 14581549
TI  - Subpopulations of equine infectious anemia virus Rev coexist in vivo and differ
      in phenotype.
AB  - Lentiviruses exist in vivo as a population of related, nonidentical genotypes,
      commonly referred to as quasispecies. The quasispecies structure is
      characteristic of complex adaptive systems and contributes to the high rate of
      evolution in lentiviruses that confounds efforts to develop effective vaccines
      and antiviral therapies. Here, we describe analyses of genetic data from
      longitudinal studies of genetic variation in a lentivirus regulatory protein,
      Rev, over the course of disease in ponies experimentally infected with equine
      infectious anemia virus. As observed with other lentivirus data, the Rev variants
      exhibited a quasispecies character. Phylogenetic and partition analyses suggested
      that the Rev quasispecies comprised two distinct subpopulations that coexisted
      during infection. One subpopulation appeared to accumulate changes in a linear,
      time-dependent manner, while the other evolved radially from a common variant.
      Over time, the two subpopulations cycled in predominance coincident with changes
      in the disease state, suggesting that the two groups differed in selective
      advantage. Transient expression assays indicated the two populations differed
      significantly in Rev nuclear export activity. Chimeric proviral clones containing
      Rev genotypes representative of each population differed in rate and overall
      level of virus replication in vitro. The coexistence of genetically distinct
      viral subpopulations that differ in phenotype provides great adaptability to
      environmental changes within the infected host. A quasispecies model with
      multiple subpopulations may provide additional insight into the nature of
      lentivirus reservoirs and the evolution of antigenic and drug-resistant variants.

PMID- 14581550
TI  - Intracellularly expressed single-domain antibody against p15 matrix protein
      prevents the production of porcine retroviruses.
AB  - The presence of porcine endogenous retroviruses presents a potential risk of
      transmission of infectious diseases (xenozoonosis) if tissues and organs from
      genetically modified pigs are to be used in xenotransplantation. Here, we report
      that intracellular expression of a llama single-domain antibody against p15, the
      matrix domain protein of the porcine endogenous retrovirus Gag polyprotein,
      blocks retrovirus production, providing the possibility of eliminating the risk
      of infection in xenotransplantation.

PMID- 14581551
TI  - Human immunodeficiency virus type 1 enters primary human brain microvascular
      endothelial cells by a mechanism involving cell surface proteoglycans independent
      of lipid rafts.
AB  - Several studies have reported a crucial role for cholesterol-enriched membrane
      lipid rafts and cell-associated heparan sulfate proteoglycans (HSPGs), a class of
      molecules that can localize in lipid rafts, in the entry of human
      immunodeficiency virus type 1 (HIV-1) into permissive cells. For the present
      study, we examined the role of these cell surface moieties in HIV-1 entry into
      primary human brain microvascular endothelial cells (BMVECs), which represent an
      important HIV-1 central nervous system-based cell reservoir and a portal for
      neuroinvasion. Cellular cholesterol was depleted by exposure to beta
      cyclodextrins and 3-hydroxy-3-methylglutaryl (HMG)-coenzyme A reductase
      inhibitors (statins), the loss of cholesterol was quantitated, and disruption of
      membrane rafts was verified by immunofluorescence. Nevertheless, these treatments
      did not affect binding of several strains of HIV-1 virions to BMVECs at 4 degrees
      C or their infectivities at 37 degrees C. In contrast, we confirmed that
      cholesterol depletion and raft disruption strongly inhibited HIV-1 binding and
      infection of Jurkat T cells. Enzymatic digestion of cell-associated HSPGs on
      human BMVECs dramatically inhibited HIV-1 infection, and our data from
      quantitative HIV-1 DNA PCR analysis strongly suggest that cell-associated
      chondroitin sulfate proteoglycans greatly facilitate infective entry of HIV-1
      into human BMVECs. These findings, in combination with our earlier work showing
      that human BMVECs lack CD4, indicate that the molecular mechanisms for HIV-1
      entry into BMVECs are fundamentally different from that of viral entry into T
      cells, in which lipid rafts, CD4, and probably HSPGs play important roles.

PMID- 14581553
TI  - Viral blip dynamics during highly active antiretroviral therapy.
AB  - Although intermittent episodes of low-level viremia are often observed in well
      suppressed highly active antiretroviral therapy (HAART)-treated patients, the
      timing and amplitude of viral blips have never been examined in detail. We
      analyze here the dynamics of viral blips, i.e., plasma VL measurements of >50
      copies/ml, in 123 HAART-treated patients monitored for a mean of 2.6 years
      (range, 5 months to 5.3 years). The mean (+/- the standard deviation) blip
      frequency was 0.09 +/- 0.11/sample, with about one-third of patients showing no
      viral blips. The mean viral blip amplitude was 158 +/- 132 human immunodeficiency
      virus type 1 (HIV-1) RNA copies/ml. Analysis of the blip frequency and amplitude
      distributions suggest that two blips less than 22 days apart have a significant
      chance of being part of the same episode of viremia. The data are consistent with
      a hypothetical model in which each episode of viremia consists of a phase of VL
      rise, followed by two-phase exponential decay. Thus, the term "viral blip" may be
      a misnomer, since viral replication appears to be occurring over an extended
      period. Neither the frequency nor the amplitude of viral blips increases with
      longer periods of observation, but the frequency is inversely correlated with the
      CD4(+)-T-cell count at the start of therapy, suggesting that host-specific
      factors but not treatment fatigue are determinants of blip frequency.

PMID- 14581552
TI  - Human T-cell leukemia virus type 1 tax oncoprotein suppression of multilineage
      hematopoiesis of CD34+ cells in vitro.
AB  - Human T-cell leukemia virus type 1 (HTLV-1) and HTLV-2 are highly related viruses
      that differ in disease manifestation. HTLV-1 is the etiologic agent of adult T
      cell leukemia and lymphoma, an aggressive clonal malignancy of human CD4-bearing
      T lymphocytes. Infection with HTLV-2 has not been conclusively linked to
      lymphoproliferative disorders. We previously showed that human hematopoietic
      progenitor (CD34(+)) cells can be infected by HTLV-1 and that proviral sequences
      were maintained after differentiation of infected CD34(+) cells in vitro and in
      vivo. To investigate the role of the Tax oncoprotein of HTLV on hematopoiesis,
      bicistronic lentiviral vectors were constructed encoding the HTLV-1 or HTLV-2 tax
      genes (Tax1 and Tax2, respectively) and the green fluorescent protein marker
      gene. Human hematopoietic progenitor (CD34(+)) cells were infected with
      lentivirus vectors, and transduced cells were cultured in a semisolid medium
      permissive for the development of erythroid, myeloid, and primitive progenitor
      colonies. Tax1-transduced CD34(+) cells displayed a two- to fivefold reduction in
      the total number of hematopoietic clonogenic colonies that arose in vitro, in
      contrast to Tax2-transduced cells, which showed no perturbation of hematopoiesis.
      The ratio of colony types that developed from Tax1-transduced CD34(+) cells
      remained unaffected, suggesting that Tax1 inhibited the maturation of relatively
      early, uncommitted hematopoietic stem cells. Since previous reports have linked
      Tax1 expression with initiation of apoptosis, lentiviral vector-mediated
      transduction of Tax1 or Tax2 was investigated in CEM and Jurkat T-cell lines.
      Ectopic expression of either Tax1 or Tax2 failed to induce apoptosis in T-cell
      lines. These data demonstrate that Tax1 expression perturbs development and
      maturation of pluripotent hematopoietic progenitor cells, an activity that is not
      displayed by Tax2, and that the suppression of hematopoiesis is not attributable
      to induction of apoptosis. Since hematopoietic progenitor cells may serve as a
      latently infected reservoir for HTLV infection in vivo, the different abilities
      of HTLV-1 and -2 Tax to suppress hematopoiesis may play a role in the respective
      clinical outcomes after infection with HTLV-1 or -2.

PMID- 14581554
TI  - Colocalization and interaction of the porcine arterivirus nucleocapsid protein
      with the small nucleolar RNA-associated protein fibrillarin.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) replicates in the
      cytoplasm of infected cells, but its nucleocapsid (N) protein localizes
      specifically to the nucleus and nucleolus. The mechanism of nuclear translocation
      and whether N associates with particular nucleolar components are unknown. In the
      present study, we show by confocal microscopy that the PRRSV N protein
      colocalizes with the small nucleolar RNA (snoRNA)-associated protein fibrillarin.
      Direct and specific interaction of N with fibrillarin was demonstrated in vivo by
      the mammalian two-hybrid assay in cells cotransfected with the N and fibrillarin
      genes and in vitro by the glutathione S-transferase pull-down assay using the
      expressed fibrillarin protein. Using a series of deletion mutants, the
      interactive domain of N with fibrillarin was mapped to a region of amino acids 30
      to 37. For fibrillarin, the first 80 amino acids, which contain the glycine
      arginine-rich region (the GAR domain), was determined to be the domain
      interactive with N. The N protein was able to bind to the full-length genomic RNA
      of PRRSV, and the RNA binding domain was identified as the region overlapping
      with the nuclear localization signal situated at positions 41 to 47. These
      results suggest that the N protein nuclear transport may be controlled by the
      binding of RNA to N. The PRRSV N protein was also able to bind to both 28S and
      18S ribosomal RNAs. The protein-protein interaction between N and fibrillarin was
      RNA dependent but independent of N protein phosphorylation. Taken together, our
      studies demonstrate a specific interaction of the PRRSV nucleocapsid protein with
      the host cell protein fibrillarin in the nucleolus, and they imply a potential
      linkage of viral strategies for the modulation of host cell functions, possibly
      through rRNA precursor processing and ribosome biogenesis.

PMID- 14581555
TI  - The N- and C-terminal regions of rotavirus NSP5 are the critical determinants for
      the formation of viroplasm-like structures independent of NSP2.
AB  - Molecular events and the interdependence of the two rotavirus nonstructural
      proteins, NSP5 and NSP2, in producing viroplasm-like structures (VLS) were
      previously evaluated by using transient cellular coexpression of the genes for
      the two proteins, and VLS domains as well as the NSP2-binding region of NSP5 were
      mapped in the context of NSP2. Review of the previous studies led us to postulate
      that NSP2 binding of NSP5 may block the N terminus of NSP5 or render it
      inaccessible and that any similar N-terminal blockage may render NSP5 alone
      capable of producing VLS independent of NSP2. This possibility was addressed in
      this report by using two forms of NSP5-green fluorescent protein (GFP) chimeras
      wherein GFP is fused at either the N or the C terminus of NSP5 (GFP-NSP5 and NSP5
      GFP) and evaluating their VLS-forming capability (by light and electron
      microscopy) and phosphorylation and multimerization potential independent of
      NSP2. Our results demonstrate that NSP5 alone can form VLS when the N terminus is
      blocked by fusion with a nonrotavirus protein (GFP-NSP5) but the C terminus is
      unmodified. Only GFP-NSP5 was able to undergo hyperphosphorylation and
      multimerization with the native form of NSP5, emphasizing the importance of an
      unmodified C terminus for these events. Deletion analysis of NSP5 mapped the
      essential signals for VLS formation to the C terminus and clearly suggested that
      hyperphosphorylation of NSP5 is not required for VLS formation. The present study
      emphasizes in general that when fusion proteins are used for functional studies,
      constructs that represent fusions at both the N and the C termini of the protein
      should be evaluated.

PMID- 14581556
TI  - Engineered retargeting of viral RNA replication complexes to an alternative
      intracellular membrane.
AB  - Positive-strand RNA virus replication complexes are universally associated with
      intracellular membranes, although different viruses use membranes derived from
      diverse and sometimes multiple organelles. We investigated whether unique
      intracellular membranes are required for viral RNA replication complex formation
      and function in yeast by retargeting protein A, the Flock House virus (FHV) RNA
      dependent RNA polymerase. Protein A, the only viral protein required for FHV RNA
      replication, targets and anchors replication complexes to outer mitochondrial
      membranes in part via an N-proximal sequence that contains a transmembrane
      domain. We replaced the FHV protein A mitochondrial outer membrane-targeting
      sequence with the N-terminal endoplasmic reticulum (ER)-targeting sequence from
      the yeast NADP cytochrome P450 oxidoreductase or inverted C-terminal ER-targeting
      sequences from the hepatitis C virus NS5B polymerase or the yeast t-SNARE Ufe1p.
      Confocal immunofluorescence microscopy confirmed that protein A chimeras
      retargeted to the ER. FHV subgenomic and genomic RNA accumulation in yeast
      expressing ER-targeted protein A increased 2- to 13-fold over that in yeast
      expressing wild-type protein A, despite similar protein A levels. Density
      gradient flotation assays demonstrated that ER-targeted protein A remained
      membrane associated, and in vitro RNA-dependent RNA polymerase assays
      demonstrated an eightfold increase in the in vitro RNA synthesis activity of the
      ER-targeted FHV RNA replication complexes. Electron microscopy showed a change in
      the intracellular membrane alterations from a clustered mitochondrial
      distribution with wild-type protein A to the formation of perinuclear layers with
      ER-targeted protein A. We conclude that specific intracellular membranes are not
      required for FHV RNA replication complex formation and function.

PMID- 14581557
TI  - Generation of a recombinant cytomegalovirus for expression of a hantavirus
      glycoprotein.
AB  - A cytomegalovirus (CMV) was isolated from its natural host, Peromyscus
      maniculatus, and was designated Peromyscus CMV (PCMV). A recombinant PCMV was
      constructed that contained Sin Nombre virus glycoprotein G1 (SNV-G1) fused in
      frame to the enhanced green fluorescent protein (EGFP) gene inserted into a site
      homologous to the human CMV UL33 (P33) gene. The recombinant CMV was used for
      expression and immunization of deer mice against SNV-G1. The results of the study
      indicate that P. maniculatus could be infected with as few as 10 virus particles
      of recombinant virus. Challenge of P. maniculatus with either recombinant or wild
      type PCMV produced no overt pathology in infected animals. P. maniculatus
      immunized with recombinant virus developed an antibody response to SNV and EGFP.
      When rechallenged with recombinant virus, animals exhibited an anamnestic
      response against SNV. Interestingly, a preexisting immune response against PCMV
      did not prevent reinfection with recombinant PCMV.

PMID- 14581558
TI  - Structures of host range-controlling regions of the capsids of canine and feline
      parvoviruses and mutants.
AB  - Canine parvovirus (CPV) and feline panleukopenia virus (FPV) differ in their
      ability to infect dogs and dog cells. Canine cell infection is a specific
      property of CPV and depends on the ability of the virus to bind the canine
      transferrin receptor (TfR), as well as other unidentified factors. Three regions
      in the capsid structure, located around VP2 residues 93, 300, and 323, can all
      influence canine TfR binding and canine cell infection. These regions were
      compared in the CPV and FPV capsid structures that have been determined, as well
      as in two new structures of CPV capsids that contain substitutions of the VP2 Asn
      93 to Asp and Arg, respectively. The new structures, determined by X-ray
      crystallography to 3.2 and 3.3 A resolutions, respectively, clearly showed
      differences in the interactions of residue 93 with an adjacent loop on the capsid
      surface. Each of the three regions show small differences in structure, but each
      appears to be structurally independent of the others, and the changes likely act
      together to affect the ability of the capsid to bind the canine TfR and to infect
      canine cells. This emphasizes the complex nature of capsid alterations that
      change the virus-cell interaction to allow infection of cells from different
      hosts.

PMID- 14581559
TI  - Borna disease virus glycoprotein is required for viral dissemination in neurons.
AB  - Borna disease virus (BDV) is a nonsegmented negative-strand RNA virus with a
      tropism for neurons. Infection with BDV causes neurological diseases in a wide
      variety of animal species. Although it is known that the virus spreads from
      neuron to neuron, assembled viral particles have never been visualized in the
      brains of infected animals. This has led to the hypothesis that BDV spreads as
      nonenveloped ribonucleoproteins (RNP) rather than as enveloped viral particles.
      We assessed whether the viral envelope glycoprotein (GP) is required for neuronal
      dissemination of BDV by using primary cultures of rat hippocampal neurons. We
      show that upon in vitro infection, BDV replicated and spread efficiently in this
      system. Despite rapid virus dissemination, very few infectious viral particles
      were detectable in the culture. However, neutralizing antibodies directed against
      BDV-GP inhibited BDV spread. In addition, interference with BDV-GP processing by
      inhibiting furin-mediated cleavage of the glycoprotein blocked virus spread.
      Finally, antisense treatment with peptide nucleic acids directed against BDV-GP
      mRNA inhibited BDV dissemination, marking BDV-GP as an attractive target for
      antiviral therapy against BDV. Together, our results demonstrate that the
      expression and correct processing of BDV-GP are necessary for BDV dissemination
      in primary cultures of rat hippocampal neurons, arguing against the hypothesis
      that the virus spreads from neuron to neuron in the form of nonenveloped RNP.

PMID- 14581560
TI  - Neuroadapted yellow fever virus 17D: determinants in the envelope protein govern
      neuroinvasiveness for SCID mice.
AB  - A molecular clone of mouse-neuroadapted yellow fever 17D virus (SPYF-MN) was used
      to identify critical determinants of viral neuroinvasiveness in a SCID mouse
      model. Virus derived from this clone differs from nonneuroinvasive YF5.2iv virus
      at 29 nucleotide positions, encoding 13 predicted amino acid substitutions and 2
      substitutions in the 3' untranslated region (UTR). The virulence determinants of
      SPYF-MN for SCID mice were identified by constructing and characterizing
      intratypic viruses in which the E protein of SPYF-MN was expressed in the YF5.2iv
      background (SPYF-E) or the E protein of YF5.2iv was expressed in the SPYF-MN
      background (YF5.2-E). SPYF-E caused lethal encephalitis in young adult SCID mice
      after intraperitoneal inoculation, with average survival times and tissue virus
      burdens resembling those of mice inoculated with the parental SPYF-MN virus. To
      define which domains of the E protein are involved in neuroinvasiveness, two
      viruses were tested in which the amino acid substitutions in domains I-II and III
      were segregated. This revealed that substitutions in domain III (residues 305,
      326, and 380) were critical for the neuroinvasive phenotype, based on average
      survival times and tissue burdens of infectious virus. Comparison of growth
      properties of the various intratypic viruses in cell culture indicated that no
      inherent defects in replication efficiency were likely to account for the
      biological differences observed in these experiments. These findings demonstrate
      that the E protein is a critical factor for yellow fever virus neuropathogenesis
      in the SCID mouse model and that the neuroinvasive properties depend principally
      on functions contributed by domain III of this protein. To assess whether
      critical determinants for neuroinvasion of normal ICR mice by SPYF virus were
      also in the E protein, sequences of viruses recovered from brains of ICR mice
      succumbing to encephalitis with the parental SPYF virus were derived. No
      differences were found in the E protein; however, two substitutions were present
      in the 3' UTR compared to that of SPYF-MN, one of which is predicted to alter RNA
      secondary structure in this region. These findings suggest that the 3' UTR may
      also affect neuroinvasiveness of SPYF virus in the mouse model.

PMID- 14581561
TI  - Borna disease virus phosphoprotein represses p53-mediated transcriptional
      activity by interference with HMGB1.
AB  - Borna disease virus (BDV) is a noncytolytic, neurotropic RNA virus that has a
      broad host range in warm-blooded animals, probably including humans. Recently, it
      was demonstrated that a 24-kDa phosphoprotein (P) of BDV directly binds to a
      multifunctional protein, amphoterin-HMGB1, and inhibits its function in cultured
      neural cells (W. Kamitani, Y. Shoya, T. Kobayashi, M. Watanabe, B. J. Lee, G.
      Zhang, K. Tomonaga, and K. Ikuta, J. Virol. 75:8742-8751, 2001). This observation
      suggested that expression of BDV P may cause deleterious effects in cellular
      functions by interference with HMGB1. In this study, we further investigated the
      significance of the binding between P and HMGB1. We demonstrated that P directly
      binds to the A-box domain on HMGB1, which is also responsible for interaction
      with a tumor suppression factor, p53. Recent works have demonstrated that binding
      between HMGB1 and p53 enhances p53-mediated transcriptional activity. Thus, we
      examined whether BDV P affects the transcriptional activity of p53 by
      interference with HMGB1. Mammalian two-hybrid analysis revealed that p53 and P
      competitively interfere with the binding of each protein to HMGB1 in a p53
      deficient cell line, NCI-H1299. In addition, P was able to significantly decrease
      p53-mediated transcriptional activation of the cyclin G promoter. Furthermore, we
      showed that activation of p21(waf1) expression was repressed in cyclosporine
      treated BDV-infected cells, as well as p53-transduced NCI-H1299 cells. These
      results suggested that BDV P may be a unique inhibitor of p53 activity via
      binding to HMGB1.

PMID- 14581562
TI  - Gamma interferon is critical for neuronal viral clearance and protection in a
      susceptible mouse strain following early intracranial Theiler's murine
      encephalomyelitis virus infection.
AB  - We evaluated the role of gamma interferon (IFN-gamma) in protecting neurons from
      virus-induced injury following central nervous system infection. IFN-gamma(-/-)
      and IFN-gamma(+/+) mice of the resistant major histocompatibility complex (MHC) H
      2(b) haplotype and intracerebrally infected with Theiler's murine
      encephalomyelitis virus (TMEV) cleared virus infection from anterior horn cell
      neurons. IFN-gamma(+/+) H-2(b) mice also cleared virus from the spinal cord white
      matter, whereas IFN-gamma(-/-) H-2(b) mice developed viral persistence in glial
      cells of the white matter and exhibited associated spinal cord demyelination. In
      contrast, infection of IFN-gamma(-/-) mice of the susceptible H-2(q) haplotype
      resulted in frequent deaths and severe neurologic deficits within 16 days of
      infection compared to the results obtained for controls. Morphologic analysis
      demonstrated severe injury to spinal cord neurons in IFN-gamma(-/-) H-2(q) mice
      during early infection. More virus RNA was detected in the brain and spinal cord
      of IFN-gamma(-/-) H-2(q) mice than in those of control mice at 14 and 21 days
      after TMEV infection. Virus antigen was localized predominantly to anterior horn
      cells in infected IFN-gamma(-/-) H-2(q) mice. IFN-gamma deletion did not affect
      the humoral response directed against the virus. However, the level of expression
      of CD4, CD8, class I MHC, or class II MHC in the central nervous system of IFN
      gamma(-/-) H-2(q) mice was lower than those in IFN-gamma(+/+) H-2(q) mice.
      Finally, in vitro analysis of virus-induced death in NSC34 cells and spinal motor
      neurons showed that IFN-gamma exerted a neuroprotective effect in the absence of
      other aspects of the immune response. These data support the hypothesis that IFN
      gamma plays a critical role in protecting spinal cord neurons from persistent
      infection and death.

PMID- 14581563
TI  - Mutations in the vaccinia virus A33R and B5R envelope proteins that enhance
      release of extracellular virions and eliminate formation of actin-containing
      microvilli without preventing tyrosine phosphorylation of the A36R protein.
AB  - The spread of vaccinia virus in cell cultures is mediated by virions that adhere
      to the tips of specialized actin-containing microvilli and also by virions that
      are released into the medium. The use of a small plaque-forming A36R gene
      deletion mutant to select spontaneous second-site mutants exhibiting enhanced
      virus release was described previously. Two types of mutations were found: C
      terminal truncations of the A33R envelope protein and a single amino acid
      substitution of the B5R envelope protein. In the present study, we transferred
      each type of mutation into a wild-type virus background in order to study their
      effects in vitro and in vivo. The two new mutants conserved the enhanced virus
      release properties of the original isolates; the A33R mutant produced
      considerably more extracellular virus than the B5R mutant. The extracellular
      virus particles contained the truncated A33R protein in one case and the mutated
      B5R protein in the other. Remarkably, both mutants failed to form actin tails and
      specialized microvilli, despite the presence of an intact A36R gene. The
      synthesis of the A36R protein as well as its physical association with the
      mutated or wild-type A33R protein was demonstrated. Moreover, the A36R protein
      was tyrosine phosphorylated, a step mediated by a membrane-associated Src kinase
      that regulates the nucleation of actin polymerization. The presence of large
      numbers of adherent virions on the cell surface argued against rapid dissociation
      as having a key role in preventing actin tail formation. Thus, the A33R and B5R
      proteins may be more directly involved in the formation or stabilization of actin
      tails than had been previously thought. When mice were inoculated intranasally,
      the A33R mutant was highly attenuated and the B5R mutant was mildly attenuated
      compared to wild-type virus. Enhanced virus release, therefore, did not
      compensate for the loss of actin tails and specialized microvilli.

PMID- 14581564
TI  - Epstein-Barr virus latent membrane protein 2A activates beta-catenin signaling in
      epithelial cells.
AB  - The Epstein-Barr virus (EBV) latent membrane protein 2A (LMP2A) functions to
      maintain latency in EBV-infected B lymphocytes. Although LMP2A is nonessential
      for the immortalization of B lymphocytes by EBV, its expression in B lymphocytes
      prevents viral reactivation by blocking B-cell receptor activation and signaling.
      LMP2A also provides an antiapoptotic signal in transgenic mice that express LMP2A
      in B lymphocytes. LMP2A activates phosphatidylinositol 3-kinase (PI3K) and the
      serine/threonine kinase Akt in lymphocytes and epithelial cells. Here we show
      that EBV LMP2A activates the PI3K and beta-catenin signaling pathways in
      telomerase-immortalized human foreskin keratinocytes (HFK). LMP2A activated Akt
      in a PI3K-dependent manner, and the downstream Akt targets glycogen synthase
      kinase 3beta (GSK3beta) and the Forkhead transcription factor FKHR were
      phosphorylated and inactivated in LMP2A-expressing HFK cells. GSK3beta is a
      negative regulator of the Wnt signaling pathway, and inactivation of GSK3beta by
      LMP2A signaling led to stabilization of beta-catenin, the central oncoprotein of
      Wnt signaling. In LMP2A-expressing cells, beta-catenin accumulated in the
      cytoplasm and translocated into the nucleus via a two-step mechanism. The
      cytoplasmic accumulation of beta-catenin downstream of LMP2A was independent of
      PI3K signaling, whereas its nuclear translocation was dependent on PI3K
      signaling. In the nucleus, beta-catenin activated a reporter responsive to T-cell
      factor, and this activation was augmented by LMP2A coexpression. The Wnt pathway
      is inappropriately activated in 90% of colon cancers and is dysregulated in
      several other cancers, and these data suggest that activation of this pathway by
      LMP2A may contribute to the generation of EBV-associated cancers.

PMID- 14581565
TI  - The pseudorabies virus Us2 protein, a virion tegument component, is prenylated in
      infected cells.
AB  - The Us2 gene is conserved among alphaherpesviruses, but its function is not
      known. We demonstrate here that the pseudorabies virus (PRV) Us2 protein is
      synthesized early after infection and localizes to cytoplasmic vesicles and to
      the plasma membrane, despite the lack of a recognizable signal sequence or
      membrane-spanning domain. Us2 protein is also packaged as part of the tegument of
      mature virions. The Us2 carboxy-terminal four amino acids comprise a CAAX motif,
      a well-characterized signal for protein prenylation. Treatment of infected cells
      with lovastatin, a drug that disrupts protein prenylation, changed the relative
      electrophoretic mobility of Us2 in sodium dodecyl sulfate-polyacrylamide gels. In
      addition, lovastatin treatment caused a dramatic relocalization of Us2 to
      cytoplasmic punctate structures associated with microtubules, which appeared to
      concentrate over the microtubule organizing center. When the CAAX motif was
      changed to GAAX and the mutant protein was synthesized from an expression
      plasmid, it concentrated in punctate cytoplasmic structures reminiscent of Us2
      localization in infected cells treated with lovastatin. We suggest that
      prenylation of PRV Us2 protein is required for proper membrane association.
      Curiously, the Us2 protein isolated from purified virions does not appear to be
      prenylated. This is the first report to describe the prenylation of an
      alphaherpesvirus protein.

PMID- 14581566
TI  - Presence of host ICAM-1 in human immunodeficiency virus type 1 virions increases
      productive infection of CD4+ T lymphocytes by favoring cytosolic delivery of
      viral material.
AB  - Although there is now convincing evidence that the infectivity of human
      immunodeficiency virus type 1 (HIV-1) is increased by incorporation of host
      intercellular adhesion molecule 1 (ICAM-1) in budding virions, the exact
      mechanism(s) through which ICAM-1 can so significantly affect HIV-1 biology
      remains obscure. To address this question, we focused our attention on the most
      proximal events in the virus life cycle. We made comparative analyses to estimate
      attachment and internalization of isogenic HIV-1 particles either lacking or
      bearing host-derived ICAM-1. Using attachment-and-entry assays and confocal
      fluorescence microscopy, we found that virus binding and uptake were both
      markedly enhanced by insertion of ICAM-1 within the virus envelope when PM1
      lymphoid cells and primary human cells (i.e., peripheral blood lymphocytes and
      purified CD4(+) T cells) were used as targets. Moreover, ICAM-1-bearing virions
      entered cells with faster uptake kinetics than viruses devoid of ICAM-1.
      Experiments conducted with fully competent viruses further confirmed the positive
      effect of virion-anchored host ICAM-1 on HIV-1 replication. Interestingly,
      subcellular-fractionation assays revealed that ICAM-1 incorporation modifies the
      HIV-1 entry route by increasing the level of viral material released in the
      cytosol, a process of internalization known to be mediated mainly by pH
      independent membrane fusion and to result in productive infection. A virion-based
      fusion assay confirmed that the acquisition of ICAM-1 increases the efficiency of
      productive HIV-1 entry in primary CD4(+) T lymphocytes. These observations
      provide new insights into how interactions other than those with gp120 and CD4
      coreceptor complex can modulate the process of productive HIV-1 infection in
      CD4(+) T lymphocytes, a cell target highly relevant to HIV-1 pathogenesis.

PMID- 14581567
TI  - Structure and function of CC-chemokine receptor 5 homologues derived from
      representative primate species and subspecies of the taxonomic suborders Prosimii
      and Anthropoidea.
AB  - A chemokine receptor from the seven-transmembrane-domain G-protein-coupled
      receptor superfamily is an essential coreceptor for the cellular entry of human
      immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV)
      strains. To investigate nonhuman primate CC-chemokine receptor 5 (CCR5) homologue
      structure and function, we amplified CCR5 DNA sequences from peripheral blood
      cells obtained from 24 representative species and subspecies of the primate
      suborders Prosimii (family Lemuridae) and Anthropoidea (families Cebidae,
      Callitrichidae, Cercopithecidae, Hylobatidae, and Pongidae) by PCR with primers
      flanking the coding region of the gene. Full-length CCR5 was inserted into
      pCDNA3.1, and multiple clones were sequenced to permit discrimination of both
      alleles. Compared to the human CCR5 sequence, the CCR5 sequences of the
      Lemuridae, Cebidae, and Cercopithecidae shared 87, 91 to 92, and 96 to 99% amino
      acid sequence homology, respectively. Amino acid substitutions tended to cluster
      in the amino and carboxy termini, the first transmembrane domain, and the second
      extracellular loop, with a pattern of species-specific changes that characterized
      CCR5 homologues from primates within a given family. At variance with humans, all
      primate species examined from the suborder Anthropoidea had amino acid
      substitutions at positions 13 (N to D) and 129 (V to I); the former change is
      critical for CD4-independent binding of SIV to CCR5. Within the Cebidae,
      Cercopithecidae, and Pongidae (including humans), CCR5 nucleotide similarities
      were 95.2 to 97.4, 98.0 to 99.5, and 98.3 to 99.3%, respectively. Despite this
      low genetic diversity, the phylogeny of the selected primate CCR5 homologue
      sequences agrees with present primate systematics, apart from some intermingling
      of species of the Cebidae and Cercopithecidae. Constructed HOS.CD4 cell lines
      expressing the entire CCR5 homologue protein from each of the Anthropoidea
      species and subspecies were tested for their ability to support HIV-1 and SIV
      entry and membrane fusion. Other than that of Cercopithecus pygerythrus, all CCR5
      homologues tested were able to support both SIV and HIV-1 entry. Our results
      suggest that the shared structure and function of primate CCR5 homologue proteins
      would not impede the movement of primate immunodeficiency viruses between
      species.

PMID- 14581568
TI  - Analysis of herpes simplex virus ICP0 promoter function in sensory neurons during
      acute infection, establishment of latency, and reactivation in vivo.
AB  - We have begun an analysis of the functional architecture of the ICP0 promoter in
      neurons in vivo with the ultimate goal of determining how this gene is regulated
      during reactivation in vivo. Promoter/reporter mutants in which the Escherichia
      coli beta-galactosidase (beta-Gal) gene was driven by various permutations of the
      ICP0 promoter were employed to permit the analysis of promoter function without
      the added complications that would arise due to inappropriate regulation of ICP0
      protein levels. A whole-ganglion immunohistochemical staining procedure (N. M.
      Sawtell, J. Virol. 77:4127-4138, 2003) was used for direct comparisons of the
      expression of the promoter/reporter gene to expression of the native protein in
      the same cell. In this way, the expression of the putative wild-type promoter
      could be validated and results for mutant promoters could be compared to
      expression of the native gene. We found that a DNA fragment from bp -562 through
      the methionine start codon of the ICP0 gene contained all sequences required for
      properly regulated ICP0 expression in diverse cell types (including sensory
      neurons of the trigeminal ganglia [TG]) in vitro and in vivo, as indicated by
      colocalization of ICP0 and beta-Gal. Truncation of the ICP0 promoter to bp -145
      or -129 resulted in the loss of immediate-early (alpha) kinetics. The truncated
      promoters expressed high levels of the reporter gene with leaky late (gamma1)
      kinetics in vitro and in some cell types in vivo. Unexpectedly, the truncated
      promoters did not express in TG neurons. Thus, TAATGARAT or other sequences
      upstream of bp -145 in the ICP0 promoter are required for basal expression of
      ICP0 in neurons but are not required for basal expression in other cells in vivo.
      There was a >95% concordance between reporter and native protein expression
      detected with the 562-bp promoter in neurons during the acute stage. However,
      this was not the case during reactivation from latency in vivo, as nearly twice
      as many neurons contained detectable beta-Gal as contained detectable ICP0. This
      same 562-bp promoter/reporter cassette, when placed in the context of a latency
      associated transcript (LAT) null mutant, resulted in >95% concordance of
      expression of beta-Gal and ICP0 during reactivation in vivo. These last results
      strongly suggest that there is a posttranscriptional constraint on the expression
      of ICP0 protein during reactivation from latency and that this constraint is
      mediated by LAT.

PMID- 14581569
TI  - Human papillomavirus type 16 E7 oncoprotein can induce abnormal centrosome
      duplication through a mechanism independent of inactivation of retinoblastoma
      protein family members.
AB  - The human papillomavirus type 16 (HPV-16) E7 oncoprotein rapidly induces
      centrosome duplication errors in primary human cells, thereby increasing the
      propensity for multipolar mitoses, which can lead to chromosome missegregation
      and aneuploidy. We analyzed a series of HPV-16 E7 mutants and demonstrate that
      this biological activity of the E7 oncoprotein is mediated by sequences
      encompassing the core pRB binding site but is independent of its ability to
      inactivate the retinoblastoma tumor suppressor protein pRB and the related pocket
      proteins p107 and p130. In addition, interaction of E7 with the S4 subunit of the
      26S proteasome and dysregulation of cdc25A transcription are also dispensable for
      the induction of centrosome duplication errors. Consistent with these results,
      expression of HPV-16 E7 induces abnormal centrosome duplication in a cell line
      that lacks functional pRB and in mouse embryo fibroblasts that are deficient for
      pRB, p107, and p130. These results demonstrate that the molecular mechanism
      whereby HPV-16 E7 induces centrosome duplication errors is independent of its
      ability to inactivate pRB, p107, and p130 or to interact with the S4 proteasome
      subunit.

PMID- 14581570
TI  - Genetic and functional analysis of full-length human immunodeficiency virus type
      1 env genes derived from brain and blood of patients with AIDS.
AB  - The genetic evolution of human immunodeficiency virus type 1 (HIV-1) in the brain
      is distinct from that in lymphoid tissues, indicating tissue-specific
      compartmentalization of the virus. Few primary HIV-1 envelope glycoproteins
      (Envs) from uncultured brain tissues have been biologically well characterized.
      In this study, we analyzed 37 full-length env genes from uncultured brain biopsy
      and blood samples from four patients with AIDS. Phylogenetic analysis of
      intrapatient sequence sets showed distinct clustering of brain relative to blood
      env sequences. However, no brain-specific signature sequence was identified.
      Furthermore, there was no significant difference in the number or positions of N
      linked glycosylation sites between brain and blood env sequences. The patterns of
      coreceptor usage were heterogeneous, with no clear distinction between brain and
      blood env clones. Nine Envs used CCR5 as a coreceptor, one used CXCR4, and two
      used both CCR5 and CXCR4 in cell-to-cell fusion assays. Eight Envs could also use
      CCR3, CCR8, GPR15, STRL33, Apj, and/or GPR1, but these coreceptors did not play a
      major role in virus entry into microglia. Recognition of epitopes by the 2F5,
      T30, AG10H9, F105, 17b, and C11 monoclonal antibodies varied among env clones,
      reflecting genetic and conformational heterogeneity. Envs from two patients
      contained 28 to 32 N-glycosylation sites in gp120, compared to around 25 in lab
      strains and well-characterized primary isolates. These results suggest that HIV-1
      Envs in brain cannot be distinguished from those in blood on the basis of
      coreceptor usage or the number or positions of N-glycosylation sites, indicating
      that other properties underlie neurotropism. The study also demonstrates
      characteristics of primary HIV-1 Envs from uncultured tissues and implies that
      Env variants that are glycosylated more extensively than lab strains and well
      characterized primary isolates should be considered during development of
      vaccines and neutralizing antibodies.

PMID- 14581571
TI  - High frequency of virus-specific CD8+ T cells in the central nervous system of
      macaques chronically infected with simian immunodeficiency virus SIVmac251.
AB  - Infection with human immunodeficiency virus or simian immunodeficiency virus
      (SIV) induces virus-specific CD8(+) T cells that traffic to lymphoid and
      nonlymphoid tissues. In this study, we used Gag-specific tetramer staining to
      investigate the frequency of CD8(+) T cells in peripheral blood and the central
      nervous system of Mamu-A*01-positive SIV-infected rhesus macaques. Most of these
      infected macaques were vaccinated prior to SIVmac251 exposure. The frequency of
      Gag(181-189) CM9 tetramer-positive cells was consistently higher in the
      cerebrospinal fluid and the brain than in the blood of all animals studied and
      did not correlate with either plasma viremia or CD4(+)-T-cell level. Little or no
      infection in the brain was documented for most animals by nucleic acid sequence
      based amplification or in situ hybridization. These data suggest that this Gag
      specific response may contribute to the containment of viral replication in this
      locale.

PMID- 14581572
TI  - A lymphatic mechanism of rotavirus extraintestinal spread in the neonatal mouse.
AB  - We used the neonatal mouse model of rotavirus infection and virus strains SA11
      clone 4 (SA11-Cl4) and Rhesus rotavirus (RRV) to examine the mechanism of the
      extraintestinal spread of viruses following oral inoculation. The spread
      competent viruses, RRV and reassortant R7, demonstrated a temporal progression
      from the intestine, to the terminal ileum, to the mesenteric lymph nodes (MLN),
      and to the peripheral tissues. SA11-Cl4 was not found outside the intestine.
      Reassortant virus S7, which was unable to reach the liver in previous studies (E.
      C. Mossel and R. F. Ramig, J. Virol. 76:6502-6509, 2002), was recovered from 60%
      of the MLN, suggesting that there are multiple determinants for the spread of
      virus from the intestine to the MLN. Phenotypic segregation analysis identified
      RRV genome segment 6 (VP6) as a secondary determinant of the spread of virus to
      the MLN (P = 0.02) in reassortant viruses containing segment 7 from the spread
      incompetent parent. These data suggest that in the orally infected neonatal
      mouse, the extraintestinal spread of rotavirus occurs via a lymphatic pathway,
      and the spread phenotype is primarily determined by NSP3 and can be modified by
      VP6.

PMID- 14581573
TI  - RNA helicase domain of tobamovirus replicase executes cell-to-cell movement
      possibly through collaboration with its nonconserved region.
AB  - UR-hel, a chimeric virus obtained by replacement of the RNA helicase domain of
      tobacco mosaic virus (TMV)-U1 replicase with that from the TMV-R strain, could
      replicate similarly to TMV-U1 in protoplasts but could not move from cell to cell
      (K. Hirashima and Y. Watanabe, J. Virol. 75:8831-8836, 2001). It was suggested
      that TMV recruited both the movement protein (MP) and replicase for cell-to-cell
      movement by unknown mechanisms. Here, we found that a recombinant, UR-hel/V, in
      which the nonconserved region was derived from TMV-R in addition to the RNA
      helicase domain of replicase, could move from cell to cell. We also analyzed
      revertants isolated from UR-hel, which recovered cell-to-cell movement by their
      own abilities. We found amino acid substitutions responsible for phenotypic
      reversion only in the nonconserved region and/or RNA helicase domain but never in
      MP. Together, these data show that both the nonconserved region and the RNA
      helicase domain of replicase are involved in cell-to-cell movement. The RNA
      helicase domain of tobamovirus replicase possibly does not interact directly with
      MP but interacts with its nonconserved region to execute cell-to-cell movement.

PMID- 14581574
TI  - Relative age of proviral porcine endogenous retrovirus sequences in Sus scrofa
      based on the molecular clock hypothesis.
AB  - Porcine endogenous retroviruses (PERV) are discussed as putative infectious
      agents in xenotransplantation. PERV classes A, B, and C harbor different envelope
      proteins. Two different types of long terminal repeat (LTR) structures exist, of
      which both are present only in PERV-A. One type of LTR contains a distinct repeat
      structure in U3, while the other is repeatless, conferring a lower level of
      transcriptional activity. Since the different LTR structures are distributed
      unequally among the proviruses and, apparently, PERV is the only virus harboring
      two different LTR structures, we were interested in determining which LTR is the
      ancestor. Replication-competent viruses can still be found today, suggesting an
      evolutionary recent origin. Our studies revealed that the age of PERV is at most
      7.6 x 10(6) years, whereas the repeatless LTR type evolved approximately 3.4 x
      10(6) years ago, being the phylogenetically younger structure. The age determined
      for PERV correlates with the time of separation between pigs (Suidae, Sus scrofa)
      and their closest relatives, American-born peccaries (Tayassuidae, Pecari
      tajacu), 7.4 x 10(6) years ago.

PMID- 14581575
TI  - Requirement of varicella-zoster virus immediate-early 4 protein for viral
      replication.
AB  - Varicella-zoster virus (VZV) is an alphaherpesvirus that causes two diseases,
      chickenpox and zoster. VZV open reading frame 4 (ORF4) encodes the immediate
      early 4 (IE4) protein, which is conserved among alphaherpesvirus and has
      transactivation activity in transient transfections. To determine whether the
      ORF4 gene product is essential for viral replication, we used VZV cosmids to
      remove ORF4 from the VZV genome. Deleting ORF4 was incompatible with recovery of
      infectious virus, whereas transfections done by using repaired cosmids with ORF4
      inserted at a nonnative site yielded virus. To analyze the functional domain of
      IE4, we introduced a mutation altering the C-terminal amino acids, KYFKC (K443S),
      which was designed to disrupt the dimerization of IE4 protein. Transfections with
      these mutant cosmids yielded no virus, indicating that this KYFKC motif was
      essential for IE4 function.

PMID- 14581576
TI  - A bipartite late-budding domain in human immunodeficiency virus type 1.
AB  - Human immunodeficiency virus type 1 (HIV-1) encodes a PTAP motif within the p6
      domain of Gag that recruits Tsg101 and associated factors to facilitate virion
      budding. In this study, we use trans-complementation assays to demonstrate that
      the PTAP motif acts synergistically with additional p6 sequences to mediate the
      formation of infectious extracellular HIV-1 virions. These studies suggest that
      Tsg101 recruitment is necessary but not sufficient to account for late-budding
      activity exhibited by HIV-1 p6.

PMID- 14581577
TI  - Role of macrophage inflammatory protein-1alpha in T-cell-mediated immunity to
      viral infection.
AB  - The immune response to lymphocytic choriomeningitis virus in mice lacking
      macrophage inflammatory protein-1alpha (MIP-1alpha) was evaluated. Generation of
      virus-specific effector T cells is unimpaired in MIP-1alpha-deficient mice.
      Furthermore, MIP-1alpha is not required for T-cell-mediated virus control or
      virus-induced T-cell-dependent inflammation. Thus, MIP-1alpha is not mandatory
      for T-cell-mediated antiviral immunity.

PMID- 14581578
TI  - Amino acid sequences within the beta1 domain of human apolipoprotein B can
      mediate rapid intracellular degradation.
AB  - Apolipoprotein B (apoB)-48 contains a region termed the beta1 domain that is
      predicted to be composed of extensive amphipathic beta-strands. Analysis of
      truncated apoB variants revealed that sequences between the carboxyl termini of
      apoB-37 and apoB-42 governed the secretion efficiency and intracellular stability
      of apoB. Although apoB-37, apoB-34, and apoB-29 were stable and secreted
      efficiently, apoB-42 and apoB-100 were secreted poorly and were degraded by an
      acetyl-leucyl-leucyl-norleucinal (ALLN)-sensitive pathway. Amino acid sequence
      analysis suggested that a segment between the carboxyl termini of apoB-38 and
      apoB-42 was 63% homologous to fatty acid binding proteins (FABPs), which contain
      orthogonal beta-sheets. To test the hypothesis that sequences from the beta1
      domain are involved in apoB degradation, fusion proteins were created that
      contained apoB-29 linked to fragments derived from the beta1 domain of apoB or to
      liver FABP. Fusion proteins containing the beta1 domain segments apoB-34-42 or
      apoB-37-42 were degraded rapidly, whereas other fusion proteins were stable and
      secreted efficiently. Degradation was ALLN-sensitive, and the apoB-34-42 segment
      increased the association of the apoB protein with the cytosolic surface of the
      microsomal membrane. Our data suggest that the presence of specific sequences in
      the beta1 domain of human apoB increases degradation by promoting the cytosolic
      exposure of the protein, although not all regions of the beta1 domain are
      functionally equivalent.

PMID- 14581579
TI  - Gating mechanism of KATP channels: function fits form.

PMID- 14581580
TI  - Spermine is fit to block inward rectifier (Kir) channels.

PMID- 14581581
TI  - Interaction mechanisms between polyamines and IRK1 inward rectifier K+ channels.
AB  - Rectification of macroscopic current through inward-rectifier K+ (Kir) channels
      reflects strong voltage dependence of channel block by intracellular cations such
      as polyamines. The voltage dependence results primarily from the movement of K+
      ions across the transmembrane electric field, which accompanies the binding
      unbinding of a blocker. Residues D172, E224, and E299 in IRK1 are critical for
      high-affinity binding of blockers. D172 appears to be located somewhat internal
      to the narrow K+ selectivity filter, whereas E224 and E299 form a ring at a more
      intracellular site. Using a series of alkyl-bis-amines of varying length as
      calibration, we investigated how the acidic residues in IRK1 interact with amine
      groups in the natural polyamines (putrescine, spermidine, and spermine) that
      cause rectification in cells. To block the pore, the leading amine of bis-amines
      of increasing length penetrates ever deeper into the pore toward D172, while the
      trailing amine in every bis-amine binds near a more intracellular site and
      interacts with E224 and E299. The leading amine in nonamethylene-bis-amine (bis
      C9) makes the closest approach to D172, displacing the maximal number of K+ ions
      and exhibiting the strongest voltage dependence. Cells do not synthesize bis
      amines longer than putrescine (bis-C4) but generate the polyamines spermidine and
      spermine by attaching an amino-propyl group to one or both ends of putrescine.
      Voltage dependence of channel block by the tetra-amine spermine is comparable to
      that of block by the bis-amines bis-C9 (shorter) or bis-C12 (equally long), but
      spermine binds to IRK1 with much higher affinity than either bis-amine does.
      Thus, counterintuitively, the multiple amines in spermine primarily confer the
      high affinity but not the strong voltage dependence of channel block. Tetravalent
      spermine achieves a stronger interaction with the pore by effectively behaving
      like a pair of tethered divalent cations, two amine groups in its leading half
      interacting primarily with D172, whereas the other two in the trailing half
      interact primarily with E224 and E299. Thus, nature has optimized not only the
      blocker but also, in a complementary manner, the channel for producing rapid,
      high-affinity, and strongly voltage-dependent channel block, giving rise to
      exceedingly sharp rectification.

PMID- 14581582
TI  - Identification of second messenger mediating signal transduction in the olfactory
      receptor cell.
AB  - One of the biggest controversial issues in the research of olfaction has been the
      mechanism underlying response generation to odorants that have been shown to fail
      to produce cAMP when tested by biochemical assays with olfactory ciliary
      preparations. Such observations are actually the original source proposing a
      possibility for the presence of multiple and parallel transduction pathways. In
      this study the activity of transduction channels in the olfactory cilia was
      recorded in cells that retained their abilities of responding to odorants that
      have been reported to produce InsP3 (instead of producing cAMP, and therefore
      tentatively termed "InsP3 odorants"). At the same time, the cytoplasmic cNMP
      concentration ([cNMP]i) was manipulated through the photolysis of caged compounds
      to examine their real-time interactions with odorant responses. Properties of
      responses induced by both InsP3 odorants and cytoplasmic cNMP resembled each
      other in their unique characteristics. Reversal potentials of currents were 2 mV
      for InsP3 odorant responses and 3 mV for responses induced by cNMP. Current and
      voltage (I-V) relations showed slight outward rectification. Both responses
      showed voltage-dependent adaptation when examined with double pulse protocols.
      When brief pulses of the InsP3 odorant and cytoplasmic cNMP were applied
      alternatively, responses expressed cross-adaptation with each other. Furthermore,
      both responses were additive in a manner as predicted quantitatively by the
      theory that signal transduction is mediated by the increase in cytoplasmic cAMP.
      With InsP3 odorants, actually, remarkable responses could be detected in a small
      fraction of cells ( approximately 2%), explaining the observation for a small
      production of cAMP in ciliary preparations obtained from the entire epithelium.
      The data will provide evidence showing that olfactory response generation and
      adaptation are regulated by a uniform mechanism for a wide variety of odorants.

PMID- 14581583
TI  - Novel regulation of calcium inhibition of the inositol 1,4,5-trisphosphate
      receptor calcium-release channel.
AB  - The inositol 1,4,5-trisphosphate (InsP3) receptor (InsP3R), a Ca2+-release
      channel localized to the endoplasmic reticulum, plays a critical role in
      generating complex cytoplasmic Ca2+ signals in many cell types. Three InsP3R
      isoforms are expressed in different subcellular locations, at variable relative
      levels with heteromultimer formation in different cell types. A proposed reason
      for this diversity of InsP3R expression is that the isoforms are differentially
      inhibited by high cytoplasmic free Ca2+ concentrations ([Ca2+]i), possibly due to
      their different interactions with calmodulin. Here, we have investigated the
      possible roles of calmodulin and bath [Ca2+] in mediating high [Ca2+]i inhibition
      of InsP3R gating by studying single endogenous type 1 InsP3R channels through
      patch clamp electrophysiology of the outer membrane of isolated Xenopus oocyte
      nuclei. Neither high concentrations of a calmodulin antagonist nor overexpression
      of a dominant-negative Ca2+-insensitive mutant calmodulin affected inhibition of
      gating by high [Ca2+]i. However, a novel, calmodulin-independent regulation of
      [Ca2+]i inhibition of gating was revealed: whereas channels recorded from nuclei
      kept in the regular bathing solution with [Ca2+] approximately 400 nM were
      inhibited by 290 muM [Ca2+]i, exposure of the isolated nuclei to a bath solution
      with ultra-low [Ca2+] (<5 nM, for approximately 300 s) before the patch-clamp
      experiments reversibly relieved Ca2+ inhibition, with channel activities observed
      in [Ca2+]i up to 1.5 mM. Although InsP3 activates gating by relieving high
      [Ca2+]i inhibition, it was nevertheless still required to activate channels that
      lacked high [Ca2+]i inhibition. Our observations suggest that high [Ca2+]i
      inhibition of InsP3R channel gating is not regulated by calmodulin, whereas it
      can be disrupted by environmental conditions experienced by the channel, raising
      the possibility that presence or absence of high [Ca2+]i inhibition may not be an
      immutable property of different InsP3R isoforms. Furthermore, these observations
      support an allosteric model in which Ca2+ inhibition of the InsP3R is mediated by
      two Ca2+ binding sites, only one of which is sensitive to InsP3.

PMID- 14581584
TI  - Spontaneous channel activity of the inositol 1,4,5-trisphosphate (InsP3) receptor
      (InsP3R). Application of allosteric modeling to calcium and InsP3 regulation of
      InsP3R single-channel gating.
AB  - The InsP3R Ca2+ release channel has a biphasic dependence on cytoplasmic free
      Ca2+ concentration ([Ca2+]i). InsP3 activates gating primarily by reducing the
      sensitivity of the channel to inhibition by high [Ca2+]i. To determine if
      relieving Ca2+ inhibition is sufficient for channel activation, we examined
      single-channel activities in low [Ca2+]i in the absence of InsP3, by patch
      clamping isolated Xenopus oocyte nuclei. For both endogenous Xenopus type 1 and
      recombinant rat type 3 InsP3R channels, spontaneous InsP3-independent channel
      activities with low open probability Po ( approximately 0.03) were observed in
      [Ca2+]i < 5 nM with the same frequency as in the presence of InsP3, whereas no
      activities were observed in 25 nM Ca2+. These results establish the half-maximal
      inhibitory [Ca2+]i of the channel to be 1.2-4.0 nM in the absence of InsP3, and
      demonstrate that the channel can be active when all of its ligand-binding sites
      (including InsP3) are unoccupied. In the simplest allosteric model that fits all
      observations in nuclear patch-clamp studies of [Ca2+]i and InsP3 regulation of
      steady-state channel gating behavior of types 1 and 3 InsP3R isoforms, including
      spontaneous InsP3-independent channel activities, the tetrameric channel can
      adopt six different conformations, the equilibria among which are controlled by
      two inhibitory and one activating Ca2+-binding and one InsP3-binding sites in a
      manner outlined in the Monod-Wyman-Changeux model. InsP3 binding activates gating
      by affecting the Ca2+ affinities of the high-affinity inhibitory sites in
      different conformations, transforming it into an activating site. Ca2+ inhibition
      of InsP3-liganded channels is mediated by an InsP3-independent low-affinity
      inhibitory site. The model also suggests that besides the ligand-regulated gating
      mechanism, the channel has a ligand-independent gating mechanism responsible for
      maximum channel Po being less than unity. The validity of this model was
      established by its successful quantitative prediction of channel behavior after
      it had been exposed to ultra-low bath [Ca2+].

PMID- 14581585
TI  - Voltage-dependent gating of the cystic fibrosis transmembrane conductance
      regulator Cl- channel.
AB  - When excised inside-out membrane patches are bathed in symmetrical Cl--rich
      solutions, the current-voltage (I-V) relationship of macroscopic cystic fibrosis
      transmembrane conductance regulator (CFTR) Cl- currents inwardly rectifies at
      large positive voltages. To investigate the mechanism of inward rectification, we
      studied CFTR Cl- channels in excised inside-out membrane patches from cells
      expressing wild-type human and murine CFTR using voltage-ramp and -step
      protocols. Using a voltage-ramp protocol, the magnitude of human CFTR Cl- current
      at +100 mV was 74 +/- 2% (n = 10) of that at -100 mV. This rectification of
      macroscopic CFTR Cl- current was reproduced in full by ensemble currents
      generated by averaging single-channel currents elicited by an identical voltage
      ramp protocol. However, using a voltage-step protocol the single-channel current
      amplitude (i) of human CFTR at +100 mV was 88 +/- 2% (n = 10) of that at -100 mV.
      Based on these data, we hypothesized that voltage might alter the gating behavior
      of human CFTR. Using linear three-state kinetic schemes, we demonstrated that
      voltage has marked effects on channel gating. Membrane depolarization decreased
      both the duration of bursts and the interburst interval, but increased the
      duration of gaps within bursts. However, because the voltage dependencies of the
      different rate constants were in opposite directions, voltage was without large
      effect on the open probability (Po) of human CFTR. In contrast, the Po of murine
      CFTR was decreased markedly at positive voltages, suggesting that the
      rectification of murine CFTR is stronger than that of human CFTR. We conclude
      that inward rectification of CFTR is caused by a reduction in i and changes in
      gating kinetics. We suggest that inward rectification is an intrinsic property of
      the CFTR Cl- channel and not the result of pore block.

PMID- 14581586
TI  - Allosteric activation of sodium-calcium exchange activity by calcium: persistence
      at low calcium concentrations.
AB  - The activity of the cardiac Na+/Ca2+ exchanger is stimulated allosterically by
      Ca2+, but estimates of the half-maximal activating concentration have varied over
      a wide range. In Chinese hamster ovary cells expressing the cardiac Na+/Ca2+
      exchanger, the time course of exchange-mediated Ca2+ influx showed a pronounced
      lag period followed by an acceleration of Ca2+ uptake. Lag periods were absent in
      cells expressing an exchanger mutant that was not dependent on regulatory Ca2+
      activation. We assumed that the rate of Ca2+ uptake during the acceleration phase
      reflected the degree of allosteric activation of the exchanger and determined the
      value of cytosolic Ca2+ ([Ca2+]i) at which the rate of Ca2+ influx was half
      maximal (Kh). After correcting for the effects of mitochondrial Ca2+ uptake and
      fura-2 buffering, Kh values of approximately 300 nM were obtained. After an
      increase in [Ca2+]i, the activated state of the exchanger persisted following a
      subsequent reduction in [Ca2+]i to values <100 nM. Thus, within 30 s after
      termination of a transient increase in [Ca2+]i, exchange-mediated Ca2+ entry
      began without a lag period and displayed a linear rate of Ca2+ uptake in most
      cells; a sigmoidal time course of Ca2+ uptake returned 60-90 s after the
      transient increase in [Ca2+]i was terminated. Relaxation of the activated state
      was accelerated by the activity of the endoplasmic reticulum Ca2+ pump,
      suggesting that local Ca2+ gradients contribute to maintaining exchanger
      activation after the return of global [Ca2+]i to low values.

PMID- 14581587
TI  - Electrostatic control and chloride regulation of the fast gating of ClC-0
      chloride channels.
AB  - The opening and closing of chloride (Cl-) channels in the ClC family are thought
      to tightly couple to ion permeation through the channel pore. In the prototype
      channel of the family, the ClC-0 channel from the Torpedo electric organ, the
      opening-closing of the pore in the millisecond time range known as "fast gating"
      is regulated by both external and internal Cl- ions. Although the external Cl-
      effect on the fast-gate opening has been extensively studied at a quantitative
      level, the internal Cl- regulation remains to be characterized. In this study, we
      examine the internal Cl- effects and the electrostatic controls of the fast
      gating mechanism. While having little effect on the opening rate, raising [Cl-]i
      reduces the closing rate (or increases the open time) of the fast gate, with an
      apparent affinity of >1 M, a value very different from the one observed in the
      external Cl- regulation on the opening rate. Mutating charged residues in the
      pore also changes the fast-gating properties-the effects are more prominent on
      the closing rate than on the opening rate, a phenomenon similar to the effect of
      [Cl-]i on the fast gating. Thus, the alteration of fast-gate closing by charge
      mutations may come from a combination of two effects: a direct electrostatic
      interaction between the manipulated charge and the negatively charged glutamate
      gate and a repulsive force on the gate mediated by the permeant ion. Likewise,
      the regulations of internal Cl- on the fast gating may also be due to the
      competition of Cl- with the glutamate gate as well as the overall more negative
      potential brought to the pore by the binding of Cl-. In contrast, the opening
      rate of the fast gate is only minimally affected by manipulations of [Cl-]i and
      charges in the inner pore region. The very different nature of external and
      internal Cl- regulations on the fast gating thus may suggest that the opening and
      the closing of the fast gate are not microscopically reversible processes, but
      form a nonequilibrium cycle in the ClC-0 fast-gating mechanism.

PMID- 14581590
TI  - The aerodynamics of insect flight.
AB  - The flight of insects has fascinated physicists and biologists for more than a
      century. Yet, until recently, researchers were unable to rigorously quantify the
      complex wing motions of flapping insects or measure the forces and flows around
      their wings. However, recent developments in high-speed videography and tools for
      computational and mechanical modeling have allowed researchers to make rapid
      progress in advancing our understanding of insect flight. These mechanical and
      computational fluid dynamic models, combined with modern flow visualization
      techniques, have revealed that the fluid dynamic phenomena underlying flapping
      flight are different from those of non-flapping, 2-D wings on which most previous
      models were based. In particular, even at high angles of attack, a prominent
      leading edge vortex remains stably attached on the insect wing and does not shed
      into an unsteady wake, as would be expected from non-flapping 2-D wings. Its
      presence greatly enhances the forces generated by the wing, thus enabling insects
      to hover or maneuver. In addition, flight forces are further enhanced by other
      mechanisms acting during changes in angle of attack, especially at stroke
      reversal, the mutual interaction of the two wings at dorsal stroke reversal or
      wing-wake interactions following stroke reversal. This progress has enabled the
      development of simple analytical and empirical models that allow us to calculate
      the instantaneous forces on flapping insect wings more accurately than was
      previously possible. It also promises to foster new and exciting multi
      disciplinary collaborations between physicists who seek to explain the
      phenomenology, biologists who seek to understand its relevance to insect
      physiology and evolution, and engineers who are inspired to build micro-robotic
      insects using these principles. This review covers the basic physical principles
      underlying flapping flight in insects, results of recent experiments concerning
      the aerodynamics of insect flight, as well as the different approaches used to
      model these phenomena.

PMID- 14581591
TI  - Mysterious Mystacina: how the New Zealand short-tailed bat (Mystacina
      tuberculata) locates insect prey.
AB  - The New Zealand short-tailed bat Mystacina tuberculata evolved in the absence of
      terrestrial mammals and initially with few potential predators. Unusual among
      bats, it is well adapted for the capture of prey on the ground. Bats from
      Fiordland, New Zealand had relatively low wing loadings and aspect ratios adapted
      for flight in cluttered habitats. We predicted that M. tuberculata would locate
      prey in air (uncluttered space) by echolocation. Echolocation call sequences
      associated with prey capture (terminal buzzes) were heard in the field, and bats
      detected and localized prey suspended on fishing line by echolocation in a flight
      cage. The bats emitted brief, multiharmonic echolocation calls at low duty cycle
      during search phase, and 64% of calls contained most energy in the fundamental
      harmonic. Approach- and terminal-phase calls were also broadband and
      multiharmonic. We predicted that bats would not use echolocation to locate prey
      hidden on the ground in leaf litter (cluttered space). Bats seemed unable to
      locate hidden prey precisely from the air and instead hunted for such prey while
      crawling. Echolocation calls were emitted at a low repetition rate on the ground,
      suggesting that here echolocation was used for orientation and not for prey
      detection. We experimentally removed cues available to the bats and showed that
      bats located mealworms in leaf litter by listening for prey-generated noises and
      possibly by olfaction.

PMID- 14581592
TI  - Hot bees in empty broodnest cells: heating from within.
AB  - Honeybee colonies maintain brood nest temperatures of 33-36 degrees C. We
      investigated brood nest thermoregulation at the level of individual worker
      behaviour and the transfer of heat from workers to the brood. Worker bees
      contribute to the regulation of brood nest temperature by producing heat while
      sitting motionless on the caps of brood cells. We report here an additional,
      newly observed heating strategy where heating bees enter empty cells between
      sealed brood cells and remain there motionless for periods of up to 45 min.
      Individually marked worker bees on the surface of sealed brood cells maintained
      thorax temperatures (T(th)) between 32.2+/-1.0 degrees C and 38.1+/-2.5 degrees C
      (mean +/- S.D.; N=20 bees) with alternating warming and cooling periods. Most of
      the observed bees made one or several long-duration visits (>2 min) to empty
      cells within the sealed brood area. T(th) at the time bees entered a cell
      [T(th(entry))] was 34.1-42.5 degrees C (N=40). In 83% of these cell visits,
      T(th(entry)) was higher (up to 5.9 degrees C; mean 2.5+/-1.5 degrees C; N=33)
      than the mean T(th) of the same bee. High values of T(th(entry)) resulted from
      preceding heating activity on the comb surface and from warm-ups just prior to
      cell visits during which T(th) increased by up to +9.6 degrees C. Bees inside
      empty cells had mean T(th) values of 32.7+/-0.1 degrees C (resting bees) to
      40.6+/-0.7 degrees C (heat-producing bees) during long-duration cell visits
      without performing any visible work. Heating behaviour inside cells resembles
      heating behaviour on the brood cap surface in that the bees appear to be
      inactive, but repeated warmings and coolings occur and T(th) does not fall below
      the optimum brood temperature. Bees staying still inside empty cells for several
      minutes have previously been considered to be 'resting bees'. We find, however,
      that the heating bees can be distinguished from the resting bees not only by
      their higher body temperatures but also by the continuous, rapid respiratory
      movements of their abdomens. By contrast, abdominal pumping movements in resting
      bees are discontinuous and interrupted by long pauses. Heat transfer to the brood
      from individual bees on the comb surface and from bees inside empty cells was
      simulated under controlled conditions. Heating on the comb surface causes a
      strong superficial warming of the brood cap by up to 3 degrees C within 30 min.
      Heat transfer is 1.9-2.6 times more efficient when the thorax is in touch with
      the brood cap than when it is not. Heating inside empty cells raises the brood
      temperature of adjacent cells by up to 2.5 degrees C within 30 min. Heat flow
      through the comb was detectable up to three brood cells away from the heated
      thorax.

PMID- 14581593
TI  - Bone formation is not impaired by hibernation (disuse) in black bears Ursus
      americanus.
AB  - Disuse by bed rest, limb immobilization or space flight causes rapid bone loss by
      arresting bone formation and accelerating bone resorption. This net bone loss
      increases the risk of fracture upon remobilization. Bone loss also occurs in
      hibernating ground squirrels, golden hamsters, and little brown bats by arresting
      bone formation and accelerating bone resorption. There is some histological
      evidence to suggest that black bears Ursus americanus do not lose bone mass
      during hibernation (i.e. disuse). There is also evidence suggesting that muscle
      mass and strength are preserved in black bears during hibernation. The question
      of whether bears can prevent bone loss during hibernation has not been
      conclusively answered. The goal of the current study was to further assess bone
      metabolism in hibernating black bears. Using the same serum markers of bone
      remodeling used to evaluate human patients with osteoporosis, we assayed serum
      from five black bears, collected every 10 days over a 196-day period, for bone
      resorption and formation markers. Here we show that bone resorption remains
      elevated over the entire hibernation period compared to the pre-hibernation
      period, but osteoblastic bone formation is not impaired by hibernation and is
      rapidly accelerated during remobilization following hibernation.

PMID- 14581594
TI  - Ventricular haemodynamics in Python molurus: separation of pulmonary and systemic
      pressures.
AB  - Vascular pressure separation by virtue of a two-chambered ventricle evolved
      independently in mammals and birds from a reptilian ancestor with a single
      ventricle, and allowed for high systemic perfusion pressure while protecting the
      lungs from oedema. Within non-crocodilian reptiles, ventricular pressure
      separation has only been observed in varanid lizards and has been regarded as a
      unique adaptation to an active predatory life style and high metabolic rate. The
      systemic and pulmonary sides of the ventricle in Python molurus are well
      separated by the muscular ridge, and a previous study using in situ perfusion of
      the heart revealed a remarkable flow separation and showed that the systemic side
      can sustain higher output pressures than the pulmonary side. Here we extend these
      observations by showing that systemic blood pressure P(sys) exceeded pulmonary
      pressure P(pul) almost seven times (75.7+/-4.2 versus 11.6+/-1.1 cm H(2)O). The
      large pressure difference between the systemic and pulmonary circulation
      persisted when P(sys) was altered by infusion of sodium nitroprusside or
      phenylephrine. Intraventricular pressures, measured in anaesthetised snakes,
      showed an overlap in the pressure profile between the pulmonary side of the
      ventricle (cavum pulmonale) and the pulmonary artery, while the higher pressure
      in the systemic side of the ventricle (cavum arteriosum) overlapped with the
      pressure in the right aortic arch. This verifies that the pressure differences
      originate within the ventricle, indicating that the large muscular ridge
      separates the ventricle during cardiac contraction.

PMID- 14581595
TI  - Catecholamine secretion in trout chromaffin cells experiencing nicotinic receptor
      desensitization is maintained by non-cholinergic neurotransmission.
AB  - The goal of the present study was to assess the catecholamine secretory
      capabilities of rainbow trout Oncorhynchus mykiss chromaffin cells experiencing
      desensitization of the nicotinic receptor. It was hypothesized that the potential
      to secrete catecholamines could be maintained under conditions of nicotinic
      receptor desensitization owing to activation of non-cholinergic release pathways.
      An in situ model for chromaffin cell nicotinic receptor desensitization was
      developed by perfusing a posterior cardinal vein preparation with saline
      containing 10(-5) mol l(-1) nicotine. Under such conditions of desensitization,
      the chromaffin cells were largely unresponsive to high-frequency (20 Hz)
      electrical stimulation; the minimal remaining secretory response was abolished by
      addition of the nicotinic receptor antagonist hexamethonium (10(-3) mol l(-1)).
      In marked contrast, however, the capacity to secrete catecholamines in response
      to low-frequency (1 Hz) electrical stimulation was unaffected by nicotinic
      receptor desensitization or by cholinergic receptor blockade (hexamethonium plus
      atropine). In preparations experiencing nicotinic receptor desensitization, the
      stimulatory effect of low-frequency (1 Hz) stimulation on catecholamine secretion
      was reduced by 43% in the presence of the VPAC receptor antagonist, VIP(6-28).
      The stimulatory effect of high-frequency (20 Hz) stimulation was unaffected by
      VIP(6-28). Catecholamine secretion evoked by cod VIP (10(-11) mol kg(-1)) and
      homologous angiotensin II ([Asn(1), Val(5)] Ang II; 5 x 10(-7) mol kg(-1)) was
      markedly enhanced (107 and 97%, respectively) in desensitized preparations.
      However, the secretory response to the muscarinic receptor agonist methylcholine
      (1 x 10(-3) mol kg(-1)) was unchanged by desensitization. The results of this
      study demonstrate that exploitation of non-cholinergic mechanisms, including
      peptidergic pathways activated during low-frequency neuronal stimulation, is a
      potential strategy whereby catecholamine secretion from trout chromaffin cells
      can be maintained during periods of nicotinic receptor desensitization.

PMID- 14581596
TI  - Limits to sustained energy intake. VI. Energetics of lactation in laboratory mice
      at thermoneutrality.
AB  - The limits to sustained energy intake are important because of their implications
      for reproductive output, foraging behaviour and thermoregulatory capabilities.
      Recent attempts to elucidate the nature of the limits to sustained energy intake
      have focused on peak lactation, which is the most energetically demanding period
      for female mammals. The hypothesis that performance of lactating animals is
      limited peripherally by the capacity of mammary glands to produce milk has
      received the most attention. However, some empirical data cannot be explained by
      the peripheral limitation hypothesis. Here, we present a novel hypothesis that
      the limits to sustained energy intake at peak lactation are imposed by the
      capacity of the animal to dissipate body heat generated as a by-product of
      processing food and producing milk. To test the heat dissipation limit hypothesis
      we challenged reproducing MF1 laboratory mice (N=67) with a reduced potential
      heat flow between the animal and the environment by exposing them to 30 degrees C
      (thermoneutral zone). We compared their food intake and reproductive output at
      peak lactation with animals studied previously at 21 degrees C (N=71) and 8
      degrees C (N=15). Mice lactating at 30 degrees C had a significantly lower mean
      asymptotic food intake (12.4 g day(-1)) than those at 21 degrees C (23.5 g day(
      1)) and 8 degrees C (28.6 g day(-1)). On average, mice at 30 degrees C raised
      significantly fewer (9.8) and smaller (6.1 g) pups than those at 21 degrees C
      (11.3 pups; 7.0 g per pup) and smaller pups than those at 8 degrees C (9.6 pups;
      7.3 g per pup). Consequently, mean litter mass at 30 degrees C (56.0 g) was
      significantly lower than at 21 degrees C (77.1 g) and at 8 degrees C (68.7 g).
      The mean rate of litter mass increase at 30 degrees C (2.1 g day(-1)) was also
      lower than at 21 degrees C (3.1 g day(-1)). The reduced food intake and low
      reproductive output in mice lactating at 30 degrees C are consistent with the
      heat dissipation limit hypothesis.

PMID- 14581597
TI  - Limits to sustained energy intake. VII. Milk energy output in laboratory mice at
      thermoneutrality.
AB  - The limits to sustained energy intake at peak lactation could be imposed
      peripherally, by the capacity of the mammary glands, or centrally, by the
      capacity of the animal to dissipate body heat generated as a by-product of
      processing food and producing milk. To distinguish between the two hypotheses, we
      examined milk energy output at peak lactation in MF1 laboratory mice exposed to
      30 degrees C (N=12), 21 degrees C (N=10; published data) and 8 degrees C (N=10;
      published data). The peripheral limitation hypothesis predicts that milk energy
      output will remain constant at different temperatures, while the heat dissipation
      limit hypothesis predicts a decline in milk energy output as temperature
      increases. Since estimates of milk energy output in small mammals can vary
      depending on the calculation method used, we evaluated the milk energy output of
      mice (N=24) using four different methods: (1) as the difference between
      metabolizable energy intake and daily energy expenditure of the female, (2) from
      female water turnover, (3) from pup water turnover and (4) from the energy budget
      of the litter. We assessed these four methods by comparing their accuracy,
      precision and sensitivity to changes in parameters involved in the calculations.
      Methods 1, 3 and 4 produced similar estimates of milk energy output, while those
      derived from female water turnover were significantly lower and more variable. On
      average, mice at 30 degrees C exported significantly less energy as milk (87.7 kJ
      day(-1)) than mice at 21 degrees C (166.7 kJ day(-1)) and 8 degrees C (288.0 kJ
      day(-1)). This reduction in milk energy output at 30 degrees C was caused by a
      significant decline in both milk flow (20.0 g day(-1), 12.9 g day(-1) and 8.5 g
      day(-1) at 8 degrees C, 21 degrees C and 30 degrees C, respectively) and gross
      energy content of milk (14.6 kJ g(-1), 13.1 kJ g(-1) and 10.5 kJ g(-1) at 8
      degrees C, 21 degrees C and 30 degrees C, respectively). Milk produced at 30
      degrees C contained significantly less total solids (34.4%) than milk at 21
      degrees C (40.9%) and 8 degrees C (41.5%) and significantly less fat (20.0%) than
      milk at 21 degrees C (26.4%) and 8 degrees C (30.3%). The reduced milk energy
      output in mice exposed to 30 degrees C, paralleled by their reduced food intake
      and low reproductive output, argues against the peripheral limitation hypothesis
      and provides strong support for the heat dissipation limit hypothesis.

PMID- 14581598
TI  - Limits to sustained energy intake. VIII. Resting metabolic rate and organ
      morphology of laboratory mice lactating at thermoneutrality.
AB  - We have previously shown that the food intake and milk production of MF1
      laboratory mice lactating at 30 degrees C, 21 degrees C and 8 degrees C increase
      as temperature declines. These data suggest that mice are not limited
      peripherally by the capacity of the mammary glands to produce milk but are
      limited by the capacity of the animal to dissipate body heat generated as a by
      product of food processing and milk production. Here, we measure resting
      metabolic rate (RMR; prior to breeding and at peak lactation) and organ
      morphology (at peak lactation) in MF1 mice exposed to 30 degrees C
      (thermoneutrality) and compare these traits with the same parameters measured
      previously in mice at 21 degrees C and 8 degrees C. The masses of visceral organs
      primarily responsible for energy flux (heart, lungs, stomach, small intestine,
      large intestine, liver, pancreas, spleen and kidneys) increased as temperature
      declined. The masses of all these organs differed between mice exposed to 8
      degrees C and 21 degrees C, whereas only the masses of heart, liver and kidneys
      differed between mice at 21 degrees C and 30 degrees C. The increases in organ
      masses were paralleled by increases in RMR at peak lactation above the levels
      measured prior to breeding, with mice at 8 degrees C and 21 degrees C having
      significantly higher increases in RMR than mice at 30 degrees C (29.6 kJ day(-1),
      25.5 kJ day(-1) and 8.1 kJ day(-1), respectively). The observed changes in
      visceral organs and RMR are consistent with both the heat dissipation and
      peripheral limit hypotheses. However, mice exposed to 8 degrees C had
      substantially larger mammary glands than mice at 21 degrees C or 30 degrees C
      (2.450 g, 1.115 g and 0.956 g dry mass, respectively), which argues against the
      peripheral limitation hypothesis and is consistent with the heat dissipation
      limit hypothesis. In addition, cold exposure resulted in greater masses of brown
      adipose tissue, white adipose tissue, pelage and tail. We discuss these changes
      in the context of the potential thermoregulatory benefits from use of the heat
      generated as a by-product of milk synthesis.

PMID- 14581599
TI  - Introductory tail-flick of the Jacky dragon visual display: signal efficacy
      depends upon duration.
AB  - Many animal signals have introductory components that alert receivers. Examples
      from the acoustic and visual domains show that this effect is often achieved with
      high intensity, a simple structure and a short duration. Quantitative analyses of
      the Jacky dragon Amphibolurus muricatus visual display reveal a different design:
      the introductory tail-flick has a lower velocity than subsequent components of
      the signal, but a longer duration. Here, using a series of video playback
      experiments with a digitally animated tail, we identify the properties
      responsible for signal efficacy. We began by validating the use of the computer
      generated tail, comparing the responses to digital video footage of a lizard tail
      flick with those to a precisely matched 3-D animation (Experiment 1). We then
      examined the effects of variation in stimulus speed, acceleration, duration and
      period by expanding and compressing the time scale of the sequence (Experiment
      2). The results identified several variables that might mediate recognition. Two
      follow-up studies assessed the importance of tail-flick amplitude (Experiment 3),
      movement speed and signal duration (Experiment 4). Lizard responses to this array
      of stimuli reveal that duration is the most important characteristic of the tail
      flick, and that intermittent signalling has the same effect as continuous
      movement. We suggest that signal design may reflect a trade-off between efficacy
      and cost.

PMID- 14581600
TI  - Intrapopulational variation in the standard metabolic rate of insects:
      repeatability, thermal dependence and sensitivity (Q10) of oxygen consumption in
      a cricket.
AB  - Studies focusing on physiological variation among individuals, and its possible
      evolutionary consequences, are scarce. A trait can only be a target of natural
      selection if it is consistent over time, that is, a trait must be repeatable. In
      ectotherms it has been suggested that standard metabolic rate (MR) is related to
      Darwinian fitness, since it reflects energy usage and expenditure. The metabolic
      rate of the cricket Hophlosphyrum griseus was determined at three ambient
      temperatures. Repeatability of MR was estimated by product-moment correlation on
      residuals of body mass, as well as the thermal sensitivity of MR on an individual
      basis (individual Q(10)). The MR of H. griseus was significantly repeatable
      (r=0.53) and highly dependent on ambient temperature, and its sensitivity (Q(10))
      was dependent on the temperature range. Our estimation of MR repeatability was
      high in comparison to published studies in vertebrates. Ours is the second report
      of repeatability (i.e. consistency over time of an individual's performance
      ranking within a population) of any aspect of energy metabolism in an insect, and
      also the first study to report significant repeatability of MR. Individual Q(10)
      values revealed important interindividual variation, which reflects the existence
      of intrapopulational variability in the thermal sensitivity of MR. In addition,
      individual Q(10) values were negatively correlated between temperature ranges.
      This means that crickets having low Q(10) at low temperatures, presented high
      Q(10) at high temperatures, and vice versa. Our results suggest that MR could be
      of selective value in insects, showing consistency over time and
      intrapopulational variability in its thermal dependence. Nevertheless, its
      heritability remains to be determined.

PMID- 14581601
TI  - Use of multiple orientation cues by juvenile loggerhead sea turtles Caretta
      caretta.
AB  - Although the orientation cues used by hatchling sea turtles have been studied
      extensively, little is known about the mechanisms of orientation and navigation
      that guide older turtles. To investigate the orientation cues used by juvenile
      loggerheads Caretta caretta L., captured turtles were tethered in a water-filled
      arena located outdoors. Turtles tested under these conditions established and
      maintained headings in specific directions in the absence of wave cues, familiar
      landmarks and chemical gradients. Distorting the magnetic field around the
      anterior part of a turtle's body did not disrupt orientation if vision remained
      unimpaired. Similarly, eliminating visual cues by attaching frosted goggles did
      not disrupt orientation if the magnetic environment was undisturbed. However,
      when turtles experienced a simultaneous disruption of magnetic and visual cues,
      their orientation was altered. These results imply that sea turtles, like
      migratory birds and homing pigeons, are able to maintain headings using multiple
      sources of directional information.

PMID- 14581602
TI  - Motor control of locomotor hindlimb posture in the American alligator (Alligator
      mississippiensis).
AB  - Crocodilians are unusual among quadrupedal tetrapods in their frequent use of a
      wide variety of hindlimb postures, ranging from sprawling to a more erect high
      walk. In this study, we use synchronized kinematic videos and electromyographic
      recordings to test how the activity patterns of hindlimb muscles in American
      alligators (Alligator mississippiensis Daudin) differ between sprawling and more
      upright postures. Previous force platform analyses suggested that upright posture
      in alligators would require greater activation by hindlimb extensors to counter
      increases in the flexor moments exerted about joints by the ground reaction force
      during upright stance. Consistent with these predictions, ankle extensors
      (gastrocnemius) and knee extensors (femorotibialis internus and iliotibialis 2)
      exhibit increases in signal intensity during the use of more upright stance. Bone
      loading data also predicted that activation patterns for hip adductors spanning
      the length of the femur would not differ between sprawling and more upright
      posture. Correspondingly, motor patterns of the adductor femoris were not altered
      as posture became more upright. However, the adductor puboischiofemoralis
      externus 3, which inserts far proximally on the femur, displays significant
      increases in burst intensity that could contribute to the greater femoral
      adduction that is integral to upright posture. In contrast to patterns in
      alligators, in mammals EMG burst intensity typically decreases during the use of
      upright posture. This difference in the motor control of limb posture between
      these taxa may be related to differences in the relative sizes of their feet.
      Alligator feet are large relative to the hindlimb and, as a result, the ground
      reaction force shifts farther from the limb joints during upright steps than in
      mammals, increasing flexor moments at joints and requiring alligator extensor
      muscles to exert greater forces to keep the limb in equilibrium. However, several
      alligator hindlimb muscles show no differences in motor pattern between sprawling
      and upright posture. The wide range of motor pattern modulations between
      different postures in alligators suggests considerable independence of neural
      control among the muscles of the alligator hindlimb.

PMID- 14581603
TI  - Propulsive impulse as a covarying performance measure in the comparison of the
      kinematics of swimming and jumping in frogs.
AB  - Animals have to modulate their locomotor behavior according to changes in
      external circumstances. The locomotor requirements are expected to be most
      extreme for species that move through different physical environments, such as
      water versus land. In this study, we examine the use of the propulsive impulse as
      a covariate in the comparison of the kinematics of locomotion of a semi-aquatic
      frog Rana esculenta, across land and through water. We focused on the propulsive
      phase because it is functionally the most significant phase of the locomotor
      cycle in both jumping and swimming, and it is also the most comparable. The frog
      alters the joint angles of its legs in order to adjust its performance (i.e.
      impulse) within both locomotor modes. The kinematics and this modulation of the
      propulsive phase differ between the two modes; however, we found that the impulse
      ranges of swimming and jumping do not fully overlap. Possible explanations for
      this include larger lateral forces during swimming, a reduced force transmission
      due to a lower external load during swimming and reduced muscle recruitment due
      to differences in coordination patterns.

PMID- 14581604
TI  - The effect of elevated intraocular oxygen on organelle degradation in the
      embryonic chicken lens.
AB  - In the vertebrate lens, nuclei and other cytoplasmic organelles are degraded in
      fiber cells situated in the center of the tissue. This is believed to ensure the
      transparency of the tissue. The mechanism that triggers this process is unknown.
      We hypothesized that standing gradients of oxygen generated within the tissue may
      serve as a spatial cue for organelle degradation. To examine this possibility, we
      incubated fertilized chicken eggs under hyperoxic (50% O(2)) or normoxic (21%
      O(2)) conditions. Hyperoxic treatment was initiated on the seventh day of
      embryonic development (E7), five days before organelle degradation normally
      commences in the lens core. Hyperoxia was maintained until E17. Under normoxic
      conditions, the partial pressure of oxygen (P(O)) within the vitreous compartment
      was low. Direct measurement of P(O) using an optode oxygen sensor indicated
      values of 1.3 kPa and 0.4 kPa for the mid- and anterior vitreous, respectively.
      Similarly, treatment with pimonidazole, a bio-reductive hypoxia marker, led to
      the formation of immuno-positive protein adducts within the lens, suggesting that
      the embryonic lens is chronically hypoxic in situ. Following hyperoxic treatment,
      vitreous P(O) significantly increased, although pimonidazole staining in the lens
      was not markedly affected. Confocal microscopy of slices prepared from hyperoxic
      lenses revealed a significant increase in the size of the lens relative to age
      matched normoxic controls. By E13, an organelle-free zone (OFZ) was present in
      the center of normoxic and hyperoxic lenses. However, in hyperoxic lenses, the
      OFZ was consistently smaller, and the distance from the lens surface to the
      border of the OFZ significantly larger, than in normoxic controls. These
      observations suggest that hyperoxia delays organelle breakdown and are consistent
      with a model in which hypoxia in the deep cortical layers of the normal lens
      serves as a trigger for the organelle loss process.

PMID- 14581605
TI  - Three-dimensional hindlimb kinematics of water running in the plumed basilisk
      lizard (Basiliscus plumifrons).
AB  - Much of what is known about tetrapod locomotion is based upon movement over solid
      surfaces. Yet in the wild, animals are forced to move over substrates with widely
      varying properties. Basilisk lizards are unique in their ability to run across
      water from the time they hatch to adulthood. Previous studies have developed
      mechanical models or presented theoretical analyses of running across water, but
      no detailed kinematic descriptions of limb motion are currently available. The
      present study reports the first three-dimensional kinematic descriptions of
      plumed basilisk lizards (Basiliscus plumifrons) running across water, from
      hatchling (2.8 g) to adult (78 g) size range. Basilisks ran on a 4.6 m-long water
      track and were filmed with two synchronized high-speed cameras at 250 frames s(
      1) and 1/1250 s shutter speed. All coordinates were transformed into three
      dimensions using direct linear transformation. Seventy-six kinematic variables
      and six morphological variables were measured or calculated to describe the
      motion of the hindlimb, but only 32 variables most relevant to kinematic motion
      are presented here. Kinematic variation among individuals was primarily related
      to size differences rather than sprint speed. Although basilisk lizards applied
      some of the same strategies to increase running velocity across water as other
      tetrapods do on land, their overall kinematics differ dramatically. The feet
      exhibit much greater medio-lateral excursions while running through water than do
      those of other lizards while running on land. Also, whereas the hindlimb
      kinematics of other lizards on land are typically symmetrical (i.e. limb
      excursions anterior to the hip are of similar magnitude to the limb excursions
      aft of the hip), basilisks running through water exhibit much greater excursions
      aft than they do anterior to the hip. Finally, ankle and knee flexion in early
      stance is a defining feature of a tetrapod step during terrestrial locomotion;
      yet this characteristic is missing in aquatic basilisk running. This may indicate
      that the basilisk limb acts primarily as a force producer - as opposed to a
      spring element - when locomoting on a highly damping surface such as water.

PMID- 14581606
TI  - Plasticity of repetitive DNA sequences within a bacterial (Type IV) secretion
      system component.
AB  - DNA rearrangement permits bacteria to regulate gene content and expression. In
      Helicobacter pylori, cagY, which contains an extraordinary number of direct DNA
      repeats, encodes a surface-exposed subunit of a (type IV) bacterial secretory
      system. Examining potential DNA rearrangements involving the cagY repeats
      indicated that recombination events invariably yield in-frame open reading
      frames, producing alternatively expressed genes. In individual hosts, H. pylori
      cell populations include strains that produce CagY proteins that differ in size,
      due to the predicted in-frame deletions or duplications, and elicit minimal or no
      host antibody recognition. Using repetitive DNA, H. pylori rearrangements in a
      host-exposed subunit of a conserved bacterial secretion system may permit a novel
      form of antigenic evasion.

PMID- 14581607
TI  - Immune evasion by murine melanoma mediated through CC chemokine receptor-10.
AB  - Human melanoma cells frequently express CC chemokine receptor (CCR)10, a receptor
      whose ligand (CCL27) is constitutively produced by keratinocytes. Compared with
      B16 murine melanoma, cells rendered more immunogenic via overexpression of
      luciferase, B16 cells that overexpressed both luciferase and CCR10 resisted host
      immune responses and readily formed tumors. In vitro, exposure of tumor cells to
      CCL27 led to rapid activation of Akt, resistance to cell death induced by
      melanoma antigen-specific cytotoxic T cells, and phosphatidylinositol-3-kinase
      (PI3K)-dependent protection from apoptosis induced by Fas cross-linking. In vivo,
      cutaneous injection of neutralizing antibodies to endogenous CCL27 blocked growth
      of CCR10-expressing melanoma cells. We propose that CCR10 engagement by locally
      produced CCL27 allows melanoma cells to escape host immune antitumor killing
      mechanisms (possibly through activation of PI3K/Akt), thereby providing a means
      for tumor progression.

PMID- 14581608
TI  - Impaired V(D)J recombination and lymphocyte development in core RAG1-expressing
      mice.
AB  - RAG1 and RAG2 are the lymphocyte-specific components of the V(D)J recombinase. In
      vitro analyses of RAG function have relied on soluble, highly truncated "core"
      RAG proteins. To identify potential functions for noncore regions and assess
      functionality of core RAG1 in vivo, we generated core RAG1 knockin (RAG1(c/c))
      mice. Significant B and T cell numbers are generated in RAG1(c/c) mice, showing
      that core RAG1, despite missing approximately 40% of the RAG1 sequence, retains
      significant in vivo function. However, lymphocyte development and the overall
      level of V(D)J recombination are impaired at the progenitor stage in RAG1(c/c)
      mice. Correspondingly, there are reduced numbers of peripheral RAG1(c/c) B and T
      lymphocytes. Whereas normal B lymphocytes undergo rearrangement of both JH loci,
      substantial levels of germline JH loci persist in mature B cells of RAG1(c/c)
      mice, demonstrating that DJH rearrangement on both IgH alleles is not required
      for developmental progression to the stage of VH to DJH recombination. Whereas VH
      to DJH rearrangements occur, albeit at reduced levels, on the nonselected alleles
      of RAG1(c/c) B cells that have undergone D to JH rearrangements, we do not detect
      VH to DH rearrangements in RAG1(c/c) B cells that retain germline JH alleles. We
      discuss the potential implications of these findings for noncore RAG1 functions
      and for the ordered assembly of VH, DH, and JH segments.

PMID- 14581610
TI  - CD27 promotes survival of activated T cells and complements CD28 in generation
      and establishment of the effector T cell pool.
AB  - CD27, like CD28, acts in concert with the T cell receptor to support T cell
      expansion. Using CD27(-/-) mice, we have shown earlier that CD27 determines the
      magnitude of primary and memory T cell responses to influenza virus. Here, we
      have examined the relative contributions of CD27 and CD28 to generation of the
      virus-specific effector T cell pool and its establishment at the site of
      infection (the lung), using CD27(-/-), CD28(-/-), and CD27/CD28(-/-) mice. We
      find that primary and memory CD8+ T cell responses to influenza virus are
      dependent on the collective contribution of both receptors. In the primary
      response, CD27 and CD28 impact to a similar extent on expansion of virus-specific
      T cells in draining lymph nodes. CD27 is the principle determinant for
      accumulation of virus-specific T cells in the lung because it can sustain this
      response in CD28(-/-) mice. Unlike CD28, CD27 does not affect cell cycle
      activity, but promotes survival of activated T cells throughout successive rounds
      of division at the site of priming and may do so at the site of infection as
      well. CD27 was found to rescue CD28(-/-) T cells from death at the onset of
      division, explaining its capacity to support a T cell response in absence of
      CD28.

PMID- 14581609
TI  - The balance between Pax5 and Id2 activities is the key to AID gene expression.
AB  - Pax5 activity is enhanced in activated B cells and is essential for class switch
      recombination (CSR). We show that inhibitor of differentiation (Id)2 suppresses
      CSR by repressing the gene expression of activation-induced cytidine deaminase
      (AID), which has been shown to be indispensable for CSR. Furthermore, a putative
      regulatory region of AID contains E2A- and Pax5-binding sites, and the latter
      site is indispensable for AID gene expression. Moreover, the DNA-binding activity
      of Pax5 is decreased in Id2-overexpressing B cells and enhanced in Id2(-/-) B
      cells. The kinetics of Pax5, but not E2A, occupancy to AID locus is the same as
      AID expression in primary B cells. Finally, enforced expression of Pax5 induces
      AID transcription in pro-B cell lines. Our results provide evidence that the
      balance between Pax5 and Id2 activities has a key role in AID gene expression.

PMID- 14581611
TI  - Robust singular value decomposition analysis of microarray data.
AB  - In microarray data there are a number of biological samples, each assessed for
      the level of gene expression for a typically large number of genes. There is a
      need to examine these data with statistical techniques to help discern possible
      patterns in the data. Our technique applies a combination of mathematical and
      statistical methods to progressively take the data set apart so that different
      aspects can be examined for both general patterns and very specific effects.
      Unfortunately, these data tables are often corrupted with extreme values
      (outliers), missing values, and non-normal distributions that preclude standard
      analysis. We develop a robust analysis method to address these problems. The
      benefits of this robust analysis will be both the understanding of large-scale
      shifts in gene effects and the isolation of particular sample-by-gene effects
      that might be either unusual interactions or the result of experimental flaws.
      Our method requires a single pass and does not resort to complex "cleaning" or
      imputation of the data table before analysis. We illustrate the method with a
      commercial data set.

PMID- 14581612
TI  - Abnormal osmotic regulation in trpv4-/- mice.
AB  - Osmotic homeostasis is one of the most aggressively defended physiological
      parameters in vertebrates. However, the molecular mechanisms underlying osmotic
      regulation are poorly understood. The transient receptor potential channel,
      vanilloid subfamily (TRPV4), is an osmotically activated ion channel that is
      expressed in circumventricular organs in the mammalian CNS, which is an important
      site of osmotic sensing. We have generated trpv4-null mice and observed
      abnormalities of their osmotic regulation. trpv4-/- mice drank less water and
      became more hyperosmolar than did wild-type littermates, a finding that was seen
      with and without administration of hypertonic saline. In addition, plasma levels
      of antidiuretic hormone were significantly lower in trpv4-/- mice than in wild
      type littermates after a hyperosmotic challenge. Continuous s.c. infusion of the
      antidiuretic hormone analogue, dDAVP, resulted in systemic hypotonicity in trpv4
      /- mice, despite the fact that their renal water reabsorption capacity was
      normal. Thus, the response to both hyper- and hypoosmolar stimuli is impaired in
      trpv4-/- mice. After a hyperosmolar challenge, there was markedly reduced
      expression of c-FOS in the circumventricular organ, the organum vasculosum of the
      lamina terminalis, of trpv4-/- mice compared with wild-type mice. This finding
      suggests that there is an impairment of osmotic sensing in the CNS of trpv4-/-
      mice. These data indicate that TRPV4 is necessary for the normal response to
      changes in osmotic pressure and functions as an osmotic sensor in the CNS.

PMID- 14581613
TI  - Transdifferentiation of mouse aortic smooth muscle cells to a macrophage-like
      state after cholesterol loading.
AB  - Mouse aortic smooth muscle cells (SMCs) were loaded for 72 h with cholesterol by
      using cholesterol:methyl-beta-cyclodextrin complexes, leading to approximately 2
      fold and approximately 10-fold increases in the contents of total cholesterol and
      cholesteryl ester, respectively. Foam-cell formation was demonstrated by
      accumulation of intracellular, Oil Red O-stained lipid droplets. Immunostaining
      showed decreased protein levels of smooth muscle alpha-actin and alpha
      tropomyosin and increased levels of macrophage markers CD68 and Mac-2 antigen.
      Quantitative real-time RT-PCR revealed that after cholesterol loading, the
      expression of SMC-related genes alpha-actin, alpha-tropomyosin, myosin heavy
      chain, and calponin H1 decreased (to 11.5 +/- 0.5%, 29.3 +/- 1.4%, 23.8 +/- 1.4%,
      and 3.8 +/- 0.5% of unloaded cells, respectively; P < 0.05 for all), whereas
      expression of macrophage-related genes CD68, Mac-2, and ABCA1 mRNA increased (to
      709 +/- 84%, 330 +/- 11%, and 207 +/- 13% of unloaded cells, respectively; P <
      0.05 for all), thereby demonstrating that the protein changes were regulated at
      the mRNA level. Furthermore, these changes were accompanied by a gain in
      macrophage-like function as assessed by phagocytotic activity. Expression of
      vascular cell adhesion molecule 1 and monocyte chemoattractant protein 1, known
      responders to inflammation, were not changed. In conclusion, cholesterol loading
      of SMC causes phenotypic changes regulated at the mRNA level that result in a
      transdifferentiation to a macrophage-like state. This finding suggests that not
      all foam cells in lesions may have a macrophage origin, despite what is indicated
      by immunostaining for macrophage-related markers. Furthermore, inflammatory
      changes in foam cells observed in vivo may not be simple consequences of
      cholesterol accumulation.

PMID- 14581614
TI  - The Drosophila synaptotagmin-like protein bitesize is required for growth and has
      mRNA localization sequences within its open reading frame.
AB  - The vertebrate synaptotagmin-like protein granuphilin binds to the vesicle
      trafficking proteins Rab27a and Munc18 and can modulate exocytosis of insulin
      containing secretory granules in pancreatic beta cell lines. Here, we report the
      molecular and genetic characterization of bitesize, a granuphilin homolog and the
      only Drosophila synaptotagmin-like protein. Mutations that affect bitesize have
      reduced cell size and number, resulting in smaller animals that develop slowly.
      We also show that at least two classes of bitesize transcripts are localized to
      the apical plasma membrane in polarized epithelial cells. Whereas most cis-acting
      mRNA localization sequences map to 3' untranslated regions, bitesize contains a
      2.2-kb sequence within its ORF that is necessary and sufficient for apical
      localization. Thus, we have found that bitesize is a metazoan example of a
      transcript for which all identifiable mRNA localization sequences are contained
      within the protein-coding region.

PMID- 14581615
TI  - The two rotor components of yeast mitochondrial ATP synthase are mechanically
      coupled by subunit delta.
AB  - The mitochondrial ATP synthase is made of a membrane-integrated F0 component that
      forms a proton-permeable pore through the inner membrane and a globular
      peripheral F1 domain where ATP is synthesized. The catalytic mechanism is thought
      to involve the rotation of a 10-12 c subunit ring in the F0 together with the
      gamma subunit of F1. An important and not yet resolved question is to define
      precisely how the gamma subunit is connected with the c-ring. In this study,
      using a doxycycline-regulatable expression system, we provide direct evidence
      that the rest of the enzyme can assemble without the delta subunit of F1, and we
      show that delta-less mitochondria are uncoupled because of an F0-mediated proton
      leak. Based on these observations, and taking into account high-resolution
      structural models, we propose that subunit delta plays a key role in the
      mechanical coupling of the c-ring to subunit gamma.

PMID- 14581616
TI  - Trp-cage: folding free energy landscape in explicit water.
AB  - Trp-cage is a 20-residue miniprotein, which is believed to be the fastest folder
      known so far. In this study, the folding free energy landscape of Trp-cage has
      been explored in explicit solvent by using an OPLSAA force field with periodic
      boundary condition. A highly parallel replica exchange molecular dynamics method
      is used for the conformation space sampling, with the help of a recently
      developed efficient molecular dynamics algorithm P3ME/RESPA (particle-particle
      particle-mesh Ewald/reference system propagator algorithm). A two-step folding
      mechanism is proposed that involves an intermediate state where two correctly
      formed partial hydrophobic cores are separated by an essential salt-bridge
      between residues Asp-9 and Arg-16 near the center of the peptide. This metastable
      intermediate state provides an explanation for the superfast folding process. The
      free energy landscape is found to be rugged at low temperatures, and then becomes
      smooth and funnel-like above 340 K. The lowest free energy structure at 300 K is
      only 1.50 A Calpha-RMSD (Calpha-rms deviation) from the NMR structures. The
      simulated nuclear Overhauser effect pair distances are in excellent agreement
      with the raw NMR data. The temperature dependence of the Trp-cage population,
      however, is found to be significantly different from experiment, with a much
      higher melting transition temperature above 400 K (experimental 315 K),
      indicating that the current force fields, parameterized at room temperature, need
      to be improved to correctly predict the temperature dependence.

PMID- 14581617
TI  - Paternal and maternal genomes confer opposite effects on proliferation, cell
      cycle length, senescence, and tumor formation.
AB  - Loss of imprinting is the silencing of active imprinted genes or the activation
      of silent imprinted genes, and it is one of the most common epigenetic changes
      associated with the development of a wide variety of tumors. Here, we have
      analyzed the effects that global imprinted gene expression has on cell
      proliferation and transformation. Primary mouse embryonic fibroblasts (MEFs),
      whose entire genome is either exclusively paternal (androgenetic) or maternal
      (parthenogenetic), exhibit dramatically contrasting patterns of growth. In
      comparison with biparental MEFs, andro-genetic proliferation is characterized by
      a shorter cell cycle, increased saturation density, spontaneous transformation,
      and formation of tumors at low passage number. Parthenogenetic MEFs reach a lower
      saturation density, senesce, and die. The maternally expressed imprinted genes
      p57kip2 and M6P/Igf2r retard proliferation and reduce the long-term growth of
      MEFs. In contrast, the paternally expressed growth factor Igf2 is essential for
      the long-term proliferation of all genotypes. Increased Igf2 expression in
      primary MEFs not only stimulates proliferation, but also results in their rapid
      conversion to malignancy with tumor formation of short latency. Our results
      reveal that paternally expressed imprinted genes, in the absence of maternal
      imprinted genes, predispose fibroblasts to rapid transformation. A potent factor
      in their transformation is IGF2, which on increased expression results in the
      rapid conversion of primary cells to malignancy. These results reveal a route by
      which malignant choriocarcinoma may arise from molar pregnancies. They also
      suggest that the derivation of stem cells from parthenogenetic embryos, for the
      purposes of therapeutic cloning, may be ineffective.

PMID- 14581618
TI  - Inflammation is detrimental for neurogenesis in adult brain.
AB  - New hippocampal neurons are continuously generated in the adult brain. Here, we
      demonstrate that lipopolysaccharide-induced inflammation, which gives rise to
      microglia activation in the area where the new neurons are born, strongly impairs
      basal hippocampal neurogenesis in rats. The increased neurogenesis triggered by a
      brain insult is also attenuated if it is associated with microglia activation
      caused by tissue damage or lipopolysaccharide infusion. The impaired neurogenesis
      in inflammation is restored by systemic administration of minocycline, which
      inhibits microglia activation. Our data raise the possibility that suppression of
      hippocampal neurogenesis by activated microglia contributes to cognitive
      dysfunction in aging, dementia, epilepsy, and other conditions leading to brain
      inflammation.

PMID- 14581619
TI  - Mammalian TRPV4 (VR-OAC) directs behavioral responses to osmotic and mechanical
      stimuli in Caenorhabditis elegans.
AB  - All animals detect osmotic and mechanical stimuli, but the molecular basis for
      these responses is incompletely understood. The vertebrate transient receptor
      potential channel vanilloid subfamily 4 (TRPV4) (VR-OAC) cation channel has been
      suggested to be an osmo/mechanosensory channel. To assess its function in vivo,
      we expressed TRPV4 in Caenorhabditis elegans sensory neurons and examined its
      ability to generate behavioral responses to sensory stimuli. C. elegans ASH
      neurons function as polymodal sensory neurons that generate a characteristic
      escape behavior in response to mechanical, osmotic, or olfactory stimuli. These
      behaviors require the TRPV channel OSM-9 because osm-9 mutants do not avoid nose
      touch, high osmolarity, or noxious odors. Expression of mammalian TRPV4 in ASH
      neurons of osm-9 worms restored avoidance responses to hypertonicity and nose
      touch, but not the response to odorant repellents. Mutations known to reduce
      TRPV4 channel activity also reduced its ability to direct nematode avoidance
      behavior. TRPV4 function in ASH required the endogenous C. elegans osmotic and
      nose touch avoidance genes ocr-2, odr-3, osm-10, and glr-1, indicating that TRPV4
      is integrated into the normal ASH sensory apparatus. The osmotic and mechanical
      avoidance responses of TRPV4-expressing animals were different in their
      sensitivity and temperature dependence from the responses of wild-type animals,
      suggesting that the TRPV4 channel confers its characteristic properties on the
      transgenic animals' behavior. These results provide evidence that TRPV4 can
      function as a component of an osmotic/mechanical sensor in vivo.

PMID- 14581620
TI  - Loss-of-function mutations in the human GLI2 gene are associated with pituitary
      anomalies and holoprosencephaly-like features.
AB  - Diminished Sonic Hedgehog (Shh) signaling is associated with the most common
      forebrain defect in humans, holoprosencephaly (HPE), which includes cyclopia, a
      phenotype also seen in mice and other vertebrates with defective Shh signaling.
      The secreted protein Shh acts as a crucial factor that patterns the ventral
      forebrain and is required for the division of the primordial eye field and brain
      into two discrete halves. Gli2 is one of three vertebrate transcription factors
      implicated as obligatory mediators of Shh signal transduction. Here, we show that
      loss-of-function mutations in the human GLI2 gene are associated with a
      distinctive phenotype (within the HPE spectrum) whose primary features include
      defective anterior pituitary formation and pan-hypopituitarism, with or without
      overt forebrain cleavage abnormalities, and HPE-like midfacial hypoplasia. We
      also demonstrate that these mutations lack GLI2 activity. We report on a
      functional association between GLI2 and human disease and highlight the role of
      GLI2 in human head development.

PMID- 14581621
TI  - Functional analysis of isoforms of NADPH: protochlorophyllide oxidoreductase
      (POR), PORB and PORC, in Arabidopsis thaliana.
AB  - NADPH:protochlorophyllide oxidoreductase (POR) catalyzes the light-dependent
      reduction of protochlorophyllide. To elucidate the physiological function of
      three differentially regulated POR isoforms (PORA, PORB and PORC) in Arabidopsis
      thaliana, we isolated T-DNA tagged null mutants of porB and porC. The mature
      seedlings of the mutants had normal photosynthetic competencies, showing that
      PORB and PORC are interchangeable and functionally redundant in developed plants.
      In etiolated seedlings, only porB showed a reduction in the photoactive
      protochlorophyllide and the size of prolamellar bodies (PLBs), indicating that
      PORB, as well as PORA, functioned in PLB assembly and photoactive
      protochlorophyllide formation in etiolated seedlings. When illuminated, the
      etiolated porB seedling was able to green to a similar extent as the wild type,
      whereas the greening was significantly reduced under low light conditions. During
      greening, high light irradiation increased the level of PORC protein, and the
      greening of porC was repressed under high light conditions. The porB, but not
      porC, etiolated seedling was more sensitive to the far-red block of greening than
      the wild type, which is caused by depletion of endogenous POR proteins resulting
      in photo-oxidative damage. These results suggest that, at the onset of greening,
      PLBs are important for efficient capture of light energy for photoconversion
      under various light conditions, and PORC, which is induced by high light
      irradiation, contributes to photoprotection during greening of the etiolated
      seedlings.

PMID- 14581622
TI  - Arabidopsis CAMTA family proteins enhance V-PPase expression in pollen.
AB  - The pollen-specific cis-acting region of the AVP1 gene is involved in the
      expression of the Arabidopsis V-PPase gene during pollen development. We isolate
      AtCAMTA5, which binds to the 38-bp pollen-specific cis-acting region, by one
      hybrid screening using the cis-acting region as a probe. The green fluorescent
      protein-fused AtCAMTA5 is specifically localized to the nucleus in Arabidopsis
      suspension cultured cells. The promoter-beta-glucuronidase reporter experiment
      shows the expression not only of AtCAMTA5 but also of AtCAMTA1 in pollen. In
      particular, AtCAMTA1 is specifically expressed in pollen. Both the one-hybrid
      analysis in the reporter yeast and in vivo transient effector-reporter analysis
      in Arabidopsis suspension cultured cells revealed that AtCAMTA1 could regulate
      gene expression depending on the CGCG-box within the 38-bp pollen-specific cis
      acting region. These results indicate that AtCAMTA1 as well as AtCAMTA5 possibly
      enhance AVP1 expression in pollen.

PMID- 14581623
TI  - Arabidopsis NDK1 is a component of ROS signaling by interacting with three
      catalases.
AB  - Plants sense various environmental stimuli and have specific signaling pathways
      to respond to these cues. We focused on light responsive components and found
      that NDKs were phosphorylated specifically after red light irradiation in Pisum
      sativum [Tanaka et al. (1998) J. Photochem. Photobiol. B 45: 113] and after blue
      light irradiation in Neurospora crassa [Oda and Hasunuma (1997) Mol. Gen. Genet.
      256: 593, Ogura et al. (2001) J. Biol. Chem. 276: 21228]. We performed yeast two
      hybrid screening using AtNDK1, the counterpart of NDK-P1 (Pisum sativum NDK1) in
      Arabidopsis, as bait, and isolated catalase3 (AtCat3). Interactions between
      AtNDK1-AtCAT1 and AtNDK1-AtCAT2 were also detected with the two-hybrid system.
      Non-denaturing two-dimensional gel electrophoresis of crude extracts from plants
      revealed that catalase and NDK activities co-migrated in the same area of the
      gel. Transgenic plants expressing AtNDK1 under control of the CaMV 35S promoter
      exhibited tolerance to paraquat and high ability to eliminate exogenous H2O2.
      These results indicate that AtNDK1 has a role in ROS response.

PMID- 14581624
TI  - Spontaneous mutations of the flavonoid 3'-hydroxylase gene conferring reddish
      flowers in the three morning glory species.
AB  - Among the Ipomoea plants, both Ipomoea nil and Ipomoea tricolor display bright
      blue flowers, and Ipomoea purpurea exhibits dark purple flowers. While all of
      these flowers contain cyanidin-based anthocyanin pigments, the mutants of I. nil,
      I. purpurea, and I. tricolor carrying the magenta, pink, and fuchsia alleles,
      respectively, produce reddish flowers containing pelargonidin derivatives, and
      all of them are deficient in the gene for flavonoid 3'-hydroxylase (F3'H). The
      magenta allele in I. nil is a nonsense mutation caused by a single C to T base
      transition generating the stop codon TGA, and the cultivar Violet carries the
      same mutation. Several tested pink mutants in I. purpurea carry inserts of the
      0.55-kb DNA transposable element Tip201 belonging to the Ac/Ds superfamily at the
      identical site. No excision of Tip201 from the F3'H gene could be detected, and
      both splicing and polyadenylation patterns of the F3'H transcripts were affected
      by the Tip201 integration. The fuchsia allele in I. tricolor is a single T
      insertion generating the stop codon TAG, and the accumulation of the F3'H
      transcripts was drastically reduced by the nonsense-mediated RNA decay.
      Spontaneous mutations in Ipomoea, including a possible founder mutation in the
      pink allele, are also discussed.

PMID- 14581625
TI  - Novel glyoxysomal protein kinase, GPK1, identified by proteomic analysis of
      glyoxysomes in etiolated cotyledons of Arabidopsis thaliana.
AB  - Glyoxysomes are present in etiolated cotyledons and contain enzymes for
      gluconeogenesis, which constitutes the major function of glyoxysomes. However,
      281 genes seemingly related to peroxisomal functions occur in the Arabidopsis
      genome, implying that many unidentified proteins are present in glyoxysomes. To
      better understand the functions of glyoxysomes, we performed glyoxysomal
      proteomic analysis of etiolated Arabidopsis cotyledons. Nineteen proteins were
      identified as glyoxysomal proteins, including 13 novel proteins, one of which is
      glyoxysomal protein kinase 1 (GPK1). We cloned GPK1 cDNA by RT-PCR and
      characterized GPK1. The amino acid sequence deduced from GPK1 cDNA has a
      hydrophobic region, a putative protein kinase domain, and a possible PTS1 motif.
      Immunoblot analysis using fractions collected on a Percoll density gradient
      confirmed that GPK1 is localized in glyoxysomes. Analysis of suborganellar
      localization and protease sensitivity showed that GPK1 is localized on
      glyoxysomal membranes as a peripheral membrane protein and that the putative
      kinase domain is located inside the glyoxysomes. Glyoxysomal proteins are
      phosphorylated well in the presence of various metal ions and [g-32P]ATP, and one
      of them is identified as thiolase by immunoprecipitation. Immuno-inhibition of
      phosphorylation in glyoxysomes suggested that GPK1 phosphorylates a 40-kDa
      protein. These results show that protein phosphorylation systems are operating in
      glyoxysomes.

PMID- 14581626
TI  - Rice phospholipase D isoforms show differential cellular location and gene
      induction.
AB  - Phospholipase D (PLD) has emerged as an important enzyme involved in signal
      transduction, stress responses, protein trafficking, and membrane metabolism.
      This report describes the cloning and characterization of three novel PLD genes
      from rice, designated RPLD3, RPLD4 and RPLD5. The rice PLDs, including the
      previously isolated RPLD1 and RPLD2, are similar to PLD subfamilies of
      Arabidopsis: Based on sequence homology and domain conservation, RPLD1 is most
      similar to the PLDalpha subfamily of PLDs while RPLD5 most closely resembles the
      PLDdelta type. RPLD2, 3 and 4 represent a unique subfamily, although they are
      most similar to PLDalpha. RPLD1 is located on chromosome 1, RPLD5 on chromosome
      3, and RPLD2, RPLD3, and RPLD4 are tandemly arrayed on chromosome 5.
      Transcriptional analysis reveals that RPLD1, present in healthy rice vegetative
      tissues, is induced rapidly but transiently in wounded leaf tissues. RPLD2, also
      induced by wounding, is present at lower levels but for a more prolonged duration
      than RPLD1. Immunolocalization with peptide specific antibodies to each of the
      five PLDs was used to demonstrate that the isoforms have overlapping but distinct
      patterns of distribution in healthy rice cells. RPLD1 was detected in mesophyll
      cell wall, membranes, and chloroplasts, whereas RPLD3 and RPLD4 were located
      predominantly in the chloroplasts. Labeling of RPLD2 and RPLD5 was sparse, and
      was most concentrated in the secondary walls of xylem (RPLD2) and guard cells
      (RPLD2 and RPLD5). This combined information on structural features, expression
      profiles, and cellular localization will assist the basis for dissection of PLD
      isoform function in rice.

PMID- 14581627
TI  - Ca2+-dependent cessation of cytoplasmic streaming induced by hypertonic treatment
      in Vallisneria mesophyll cells: possible role of cell wall-plasma membrane
      adhesion.
AB  - In mesophyll cells of the aquatic angiosperm Vallisneria gigantea Graebner, a
      rapid and transient inhibition of cytoplasmic streaming was induced by hypertonic
      treatment with sorbitol. Higher concentrations of sorbitol induced the response
      more rapidly and in more cells. The response to hypertonic treatment was strictly
      dependent on the presence of extracellular Ca2+ and was sensitive to Ca2+-channel
      blockers, including the stretch-activated Ca2+-channel blocker Gd3+.
      Deplasmolyzed cells never responded to a second hypertonic treatment administered
      immediately after plasmolysis and subsequent deplasmolysis. Responsiveness was
      gradually recovered during 24 h of incubation; however, cycloheximide,
      cordycepin, and trypsin completely suppressed the recovery. Although an Arg-Gly
      Asp (RGD) hexapeptide markedly disturbed the pattern of cytoplasmic streaming, it
      exhibited no specific effects on the response to hypertonic treatment or on the
      recovery of responsiveness. Taken together, our results demonstrate that leaf
      mesophyll cells in a multicellular plant can respond to mechanical stimuli and
      that a Ca2+ influx through stretch-activated Ca2+ channels plays an indispensable
      role in the response. Furthermore, the possible involvement of RGD-insensitive
      but trypsin-sensitive protein factor(s), whose function is impaired by detachment
      of the plasma membrane from the cell wall, is suggested.

PMID- 14581628
TI  - Ntdin, a tobacco senescence-associated gene, is involved in molybdenum cofactor
      biosynthesis.
AB  - To date, dozens of genes have been reported to be up-regulated with senescence in
      higher plants. Radish din1 and its ortholog sen1 of Arabidopsis are known as
      such, but their function is not clear yet. Here we have isolated their
      counterpart cDNA from tobacco and designated it as NTDIN: Its product, Ntdin, a
      185 amino acid polypeptide with 56.8% and 54.2% identity to Atsen1 and Rsdin1,
      respectively, is localized in chloroplasts. Transcripts of Ntdin are induced by
      sulfate or nitrate but not by phosphate, suggesting its involvement in sulfur and
      nitrogen metabolism. A database search revealed that Ntdin shows similarity with
      the C-terminal region of Nicotiana plumbaginifolia Cnx5, which functions in
      molybdenum cofactor (Moco) biosynthesis. Transgenic tobacco plants with
      suppressed Ntdin are more tolerant to chlorate, a substrate analog of nitrate
      reductase, than controls, implying low nitrate reductase activity in the
      transgenic plants due to a deficiency of Moco. Indeed, enzymatic activities of
      two molybdoenzymes, nitrate reductase and xanthine dehydrogenase, in transgenic
      plants are found to be significantly lower than in control plants. Direct
      measurement of Moco contents reveals that those transgenic plants contain about
      5% Moco of those of the control plants. Abscisic acid and indole-3-acidic acid,
      whose biosynthetic pathways require Moco, up-regulated Ntdin expression. Taken
      together, it is concluded that Ntdin functions in a certain step in Moco
      biosynthesis.

PMID- 14581629
TI  - Three-dimensional reconstruction of tubular structure of vacuolar membrane
      throughout mitosis in living tobacco cells.
AB  - Plant vacuoles are the largest of organelles, performing various functions in
      cellular metabolism, morphogenesis and cell division. Dynamic changes in vacuoles
      during mitosis were studied by monitoring tubular structure of vacuolar membrane
      (TVM) in living transgenic tobacco BY-2 cells stably expressing a GFP-AtVam3p
      fusion protein (BY-GV). Comprehensive images of the complicated TVM
      configurations were obtained by reconstructing three-dimensional (3-D) surface
      structures from sequential confocal sections, using newly developed software, SSR
      (stereo-structure reconstructor). Using the surface modeling technique, we
      succeeded for the first time in clarifying the development process of TVMs and
      the topological relationship between TVMs and large vacuoles. TVMs, initially
      organized from large vacuoles, elongated to encircle the spindle at metaphase.
      Subsequently, the TVMs invaded the equatorial region from anaphase to telophase,
      and then they were divided to the two daughter cells by the cell plate at
      cytokinesis. When the daughter nuclei were separating from the cell plate, some
      TVMs enlarged to form large vacuoles near the division site. Spatial analysis
      revealed that from anaphase until cytokinesis, TVMs connected the two large
      vacuoles and functioned as a route for inter-vacuolar transport. Furthermore, the
      experiments using the inhibitor for actin microfilaments indicated that the
      microfilaments were indispensable for the development and the maintenance of
      TVMs.

PMID- 14581630
TI  - Is the LIM-domain protein HaWLIM1 associated with cortical microtubules in
      sunflower protoplasts?
AB  - Flowering plants express several LIM-domain proteins related to the animal
      cystein-rich proteins. The expression of sunflower LIM genes was followed by RT
      PCR in cultured sunflower protoplasts. A transcript was detected only for
      HaWLIM1, but not for the other two genes HaPLIM1 and HaPLIM2. Polyclonal
      antibodies raised against either full length recombinant HaWLIM1 protein or
      peptides recognized a 27 kDa polypeptide on Western blots. Immunocytolocalization
      studies showed that HaWLIM1 is located in the cytoplasm and in the nucleus. In
      the cytoplasm, HaWLIM1 is localized in punctate structures, distributed along
      microtubule bundles. Depolymerizing microtubules with oryzalin resulted in a
      strong modification of the HaWLIM1 cortical pattern. In contrast, treatment of
      protoplasts with latrunculin B, which disrupts actin filaments, had no effect on
      HaWLIM1 localization. HaWLIM1 was also located within the nucleus of interphase
      protoplasts. During mitosis, nuclear labelling was observed in prophase, which
      decreased in metaphase, disappeared in anaphase, and recovered in telophase.
      These results suggest a dual role for HaWLIM1: in the cytoplasm, as a component
      of molecular complexes which may interact with microtubules, and in the nucleus,
      as a partner of transcription factors during interphase.

PMID- 14581631
TI  - Predicting the extent of photosystem II photoinactivation using chlorophyll a
      fluorescence parameters measured during illumination.
AB  - The temperature dependence of the relationship between the decline in activity of
      photosystem II (PSII) and a chlorophyll a fluorescence parameter combining the
      excitation pressure (1-qP) and efficiency of excitation energy capture by open
      PSII reaction centers in the light-acclimated state (Fv'/Fm') was investigated in
      cotton leaves. A formula for the prediction of PSII inactivation is proposed on
      the basis of the results obtained. By comparison of the predicted and actual
      levels of PSII photoinactivation, the rate of PSII recovery was estimated from
      chlorophyll a fluorescence parameters measured during the day for attached cotton
      leaves exposed to suboptimal morning temperatures in a greenhouse.

PMID- 14581632
TI  - DFL2, a new member of the Arabidopsis GH3 gene family, is involved in red light
      specific hypocotyl elongation.
AB  - A new GH3-related gene, designated DFL2, causes a short hypocotyl phenotype when
      overexpressed under red and blue light and a long hypocotyl when antisensed under
      red light conditions. Higher expression of this gene was observed in continuous
      white, blue and far-red light but the expression level was low in red light and
      darkness. DFL2 gene expression was induced transiently with red light pulse
      treatment. DFL2 transgenic plants exhibited a normal root phenotype including
      primary root elongation and lateral root formation, although primary root
      elongation was inhibited in antisense transgenic plants only under red light. The
      adult phenotypes of sense and antisense transgenic plants were not different from
      that of wild type. DFL2 promoter activity was observed in the hypocotyl. Our
      results suggest that DFL2 is located downstream of red light signal transduction
      and determines the degree of hypocotyl elongation.

PMID- 14581633
TI  - Mucilage secretion regulated by sex pheromones in Closterium peracerosum
      strigosum-littorale complex.
AB  - When mating-type plus (mt+) and minus (mt-) cells of the Closterium peracerosum
      strigosum-littorale complex were mixed in nitrogen-depleted mating medium,
      secretion of mucilage containing uronic acid from cells was markedly activated
      and the mucilage accumulated around the cells. Substances with the ability to
      stimulate mucilage secretion from mt+ and mt- cells were detected in media in
      which mt- and mt+ cells had been separately cultured, respectively. We designated
      the active substances secreted from mt+ and mt- cells mucilage secretion
      stimulating pheromone (MS-SP)-plus and MS-SP-minus, respectively. Activity of MS
      SP-plus and MS-SP-minus decreased to 20% level by incubation at 80 degrees C for
      10 min. Light was indispensable for the secretion of mucilage. The secretion of
      MS-SP-plus and MS-SP-minus decreased with dark treatment. MS-SP-plus eluted at
      around 95 k from a gel filtration column, and reacted with antibodies against two
      subunits of protoplast-release-inducing protein (PR-IP), which induces protoplast
      release from mt- cells. MS-SP-minus eluted at around 20 k from a gel filtration
      column, and reacted with an antibody against the PR-IP inducer, which induces the
      secretion of PR-IP from mt+ cells. In addition, purified PR-IP and PR-IP inducer
      stimulated mucilage secretion from mt- and mt+ cells, respectively. These results
      strongly suggested that MS-SP-plus and MS-SP-minus were the same molecules as the
      PR-IP and the PR-IP inducer, respectively.

PMID- 14581634
TI  - Plant 115-kDa actin-filament bundling protein, P-115-ABP, is a homologue of plant
      villin and is widely distributed in cells.
AB  - In many cases, actin filaments are arranged into bundles and serve as tracks for
      cytoplasmic streaming in plant cells. We have isolated an actin-filament bundling
      protein, which is composed of 115-kDa polypeptide (P-115-ABP), from the
      germinating pollen of lily, Lilium longiflorum [Nakayasu et al. (1998) BIOCHEM:
      Biophys. Res. Commun. 249: 61]. P-115-ABP shared similar antigenicity with a
      plant 135-kDa actin-filament bundling protein (P-135-ABP), a plant homologue of
      villin. A full-length cDNA clone (ABP115; accession no. AB097407) was isolated
      from an expression cDNA library of lily pollen by immuno-screening using antisera
      against P-115-ABP and P-135-ABP. The amino acid sequence of P-115-ABP deduced
      from this clone showed high homology with those of P-135-ABP and four villin
      isoforms of Arabidopsis thaliana (AtVLN1, AtVLN2, AtVLN3 and AtVLN4), especially
      AtVLN4, indicating that P-115-ABP can also be classified as a plant villin. The P
      115-ABP isolated biochemically from the germinating lily pollen was able to
      arrange F-actin filaments with uniform polarity into bundles and this bundling
      activity was suppressed by Ca2+-calmodulin (CaM), similar to the actin-filament
      bundling properties of P-135-ABP. The P-115-ABP type of plant villin was widely
      distributed in plant cells, from algae to land plants. In root hair cells of
      Hydrocharis dubia, this type of plant villin was co-localized with actin-filament
      bundles in the transvacuolar strands and the sub-cortical regions. Microinjection
      of the antiserum against P-115-ABP into living root hair cells caused the
      disappearance of transvaculor strands and alteration of the route of cytoplasmic
      streaming. In internodal cells of Chara corallina in which the P-135-ABP type of
      plant villin is lacking, the P-115-ABP type showed co-localization with actin
      filament cables anchored on the intracellular surface of chloroplasts. These
      results indicated that plant villins are widely distributed and involved in the
      organization of actin filaments into bundles throughout the plant kingdom.

PMID- 14581635
TI  - Uptake of an endocytic marker by rice cells: variations related to osmotic and
      saline stress.
AB  - Saline and osmotic stress are the main abiotic factors limiting the productivity
      of rice and other crop plants. Although both coincide in generating water deficit
      and affect many aspects of plant growth and development similarly, some effects
      of salinity are distinctively related to the ionic component of salt stress. At
      the cellular level, dessication tolerance is largely dependent on the cell's
      ability for osmotic adjustment. Here, we have studied the effects of saline and
      osmotic stress on endocytosis by rice cells, to investigate the common and
      distinctive effects of saline-generated stress and osmotically generated stress,
      and the possible involvement of endocytosis in tolerance mechanisms. For this
      purpose, we have used rice cell lines with different levels of tolerance and
      biotinylated bovine serum albumin (bBSA) as an endocytic marker, which in our
      previous experiments has been shown to enter rice cells by a process with the
      characteristics of receptor-mediated endocytosis. Our results indicate that the
      pattern of uptake is common to both types of stress. Thus, when rice cells were
      subjected to saline or osmotic stress there was an initial dose-dependent
      inhibition of uptake. However, after more extended stress periods, there was an
      activation of uptake in the stressed cells. This late activation appears mainly
      related to the inhibition of growth commonly caused by the different stress
      agents used in this study. When using cell lines with different degrees of
      tolerance, the level of uptake activation varied as a function of the type of
      stress. Thus, under osmotic stress, a higher stress tolerance was directly
      related to a higher bBSA uptake, while the opposite occurred under saline stress.
      The possible role of endocytosis in the cellular responses to osmotic and saline
      stress is discussed.

PMID- 14581636
TI  - Gravitaxis in Chlamydomonas reinhardtii studied with novel mutants.
AB  - Many free-swimming unicellular organisms show negative gravitaxis, i.e. tend to
      swim upward, although their specific densities are higher than the medium
      density. To obtain clues to the mechanism of this behavior, we examined how a
      mutation in motility or behavior affects the gravitaxis in Chlamydomonas. A
      phototaxis mutant, ptx3, deficient in membrane excitability showed weakened
      gravitaxis, whereas another phototaxis mutant, ptx1, deficient in regulation of
      flagellar dominance displayed normal gravitaxis. Two mutants that swim backwards
      only, mbo1 and mbo2, did not show any clear gravitaxis. We also isolated two
      novel mutants deficient in gravitaxis, gtx1 and gtx2. These mutants displayed
      normal motility and physical characteristics of cell body as assessed by the
      behavior of anesthetized cells. However, these cells were found to have defects
      in physiological responses involving membrane excitation. These observations are
      consistent with the idea that the gravitaxis in Chlamydomonas involves a
      physiological signal transduction system, which is at least partially independent
      of the system used for phototaxis.

PMID- 14581637
TI  - And so on ad infinitum.

PMID- 14581638
TI  - Investigation of cancer incidence and mortality at a Scottish semiconductor
      manufacturing facility.
AB  - BACKGROUND: We became aware of concern about cancer at a Scottish semiconductor
      manufacturing facility in 1998. Aim To compare cancer experience among current
      and former workers at the facility, with an appropriate comparison population,
      making use of any readily available exposure information. METHOD: We obtained
      personnel and employment episode information from four sources within the
      company. Workers were flagged for death and cancer registrations at the National
      Health Service Central Register in Edinburgh. We constructed standardized
      registration and mortality ratios (SRRs and SMRs), using Scotland as the
      comparison, with and without an adjustment for deprivation. RESULTS: The main
      mortality analysis included 4388 workers, with a mean length of follow-up of 12.5
      years. Overall mortality was substantially below that expected for men, and for
      women was slightly below expected. Total cancer registrations were close to
      expected levels for men and women. Four cancers produced noteworthy findings:
      malignant neoplasm of the trachea, bronchus and lung in women-deprivation
      adjusted SRR [95% confidence interval (CI), number of cases] 273 (136-488, 11
      cases); malignant neoplasm of the stomach in women-adjusted SRR 438 (90-1281,
      three cases); and malignant neoplasm of the female breast-adjusted SRR 134 (82
      206, 20 cases). The unadjusted SMR for male brain cancer was 401 (83-1172, three
      cases) and there was an additional non-fatal case. CONCLUSION: These findings,
      particularly those relating to lung cancer, though inconclusive, point to the
      possibility of a work-related risk of cancer that justifies further
      investigation.

PMID- 14581639
TI  - Overweight and obesity among Kuwait Oil Company employees: a cross-sectional
      study.
AB  - BACKGROUND: Overweight and obesity are considered major risk factors for many
      diseases, and their prevalence is known to be high in Kuwait from previous
      studies. AIM: To assess the prevalence of overweight and obesity and related risk
      factors among Kuwait Oil Company (KOC) employees. METHOD: A cross-sectional study
      of full-time KOC employees was carried out using a structured questionnaire that
      was completed during periodic medical examinations. The questionnaire included
      demographic details, frequency and duration of physical activity, history of
      chronic diseases and medication. All participants were counselled and examined.
      Blood pressure, body mass index and fasting glucose were recorded. RESULTS: Some
      3282 out of 3900 employees completed the study; 85% of participants were male,
      62%were field workers and 38%were office workers. The overall prevalence of
      overweight and obesity among KOC employees was 75%. Males showed a higher level
      of overweight and obesity (79%) than females (56%). Field workers had a higher
      level of overweight and obesity (78%) and higher inactivity (65%) than office
      workers (72% and 56%, respectively). CONCLUSION: Overweight and obesity, together
      with inactivity, are highly prevalent among KOC employees, and more so among
      field workers than office workers. Encouraging an active lifestyle, healthy
      eating habits and weight control programmes are all possible interventions to
      reduce the prevalence of overweight and obesity.

PMID- 14581640
TI  - A follow-up study on the association of working conditions and lifestyles with
      the development of (perceived) mental symptoms in workers of a telecommunication
      enterprise.
AB  - AIM: This study investigated the association of working conditions and lifestyle
      with mental health in Japanese workers. METHODS: A follow-up study was carried
      out in the Kanto district of Japan of workers in a telecommunications enterprise
      who received their first annual health check-up between 1992 and 1996 and were
      between 20 and 54 years old. Workers who reported mental symptoms, had a past
      history of disease, or current illness at their first check-up were excluded from
      the analysis. In total, the study included 23 837 workers. The association
      between working conditions and lifestyle and the development of mental symptoms
      was investigated by pooled logistic regression analyses. RESULTS: Working long
      hours and part-time work, as opposed to normal daytime hours of work, were
      factors associated with the development of mental symptoms in males, as were
      smoking, short sleeping hours, little physical exercise, rarely taking three
      meals a day, frequently eating within 1 h before sleep, much preference for salty
      meals and little preference for vegetables. Consumption of alcohol was negatively
      associated with the development of mental symptoms in males. Overall, the results
      suggested that the lower the Healthy Work and Lifestyle Score, the higher the
      risk of developing mental symptoms. CONCLUSIONS: Working conditions and
      lifestyle, especially food preferences, have an apparent influence on the mental
      health of Japanese workers. Moreover, the Healthy Work and Lifestyle Score
      indicates that working conditions and lifestyle appear to have a cumulative
      influence upon the mental health of Japanese workers.

PMID- 14581641
TI  - Effect of work with visual display units on musculo-skeletal disorders in the
      office environment.
AB  - BACKGROUND: The increase in computer and mouse use has been associated with an
      increased prevalence of disorders in the neck and upper extremities. Furthermore,
      poor workstation design has been associated with an increased risk of developing
      these symptoms. Aim The aims of this study were (i) to estimate the prevalence of
      musculo-skeletal disorders among full-time visual display unit (VDU) users; (ii)
      to examine how the prevalence varies by work environment; and (iii) to explore
      the association with work factors. METHOD: A survey was carried out on the effect
      of work with VDUs on musculo-skeletal disorders in workers in the office
      environment of 56 workplaces. Office workers (n = 298), customer service workers
      (n = 238) and designers (n = 247) were studied. RESULTS: For all the occupations
      combined, the 12 month prevalences of musculo-skeletal symptoms in the neck,
      shoulders, elbows, lower arms and wrists, and fingers were 63, 24, 18, 35 and
      16%, respectively. The study indicated that musculo-skeletal pain is common among
      computer workers in offices. There was no strong association between the duration
      of computer work and pain or between the duration of mouse use and pain, but
      workers' perception of their workstation as being poor ergonomically was strongly
      associated with an increased prevalence of pain. CONCLUSIONS: Musculo-skeletal
      symptoms are common, but the duration of daily keyboard and mouse use had no
      connection with musculo-skeletal symptoms. Instead, more consideration should be
      paid to the ergonomics of workstations, the placing of the mouse, the postures of
      the upper extremities and the handling of the mouse.

PMID- 14581642
TI  - Voice recognition products-an occupational risk for users with ULDs?
AB  - BACKGROUND: Voice recognition systems (VRS) allow speech to be converted both
      directly into text-which appears on the screen of a computer-and to direct
      equipment to perform specific functions. Suggested applications are many and
      varied, including increasing efficiency in the reporting of radiographs, allowing
      directed surgery and enabling individuals with upper limb disorders (ULDs) who
      cannot use other input devices, such as keyboards and mice, to carry out word
      processing and other activities. Aim This paper describes four cases of vocal
      dysfunction related to the use of such software, which have been identified from
      the database of the Voice and Speech Laboratory of the Massachusetts Eye and Ear
      infirmary (MEEI). METHOD: The database was searched using key words 'voice
      recognition' and four cases were identified from a total of 4800. RESULTS: In all
      cases, the VRS was supplied to assist individuals with ULDs who could not use
      conventional input devices. Case reports illustrate time of onset and symptoms
      experienced. CONCLUSION: The cases illustrate the need for risk assessment and
      consideration of the ergonomic aspects of voice use prior to such adaptations
      being used, particularly in those who already experience work-related ULDs.

PMID- 14581643
TI  - Occupational groups at risk of voice disorders: a review of the literature.
AB  - BACKGROUND: Occupational voice health is becoming more important as more people
      rely on their voices for their work. A number of studies have identified certain
      occupational groups at increased risk of developing occupational voice disorders,
      namely teachers, singers and aerobics instructors. Aim The paper aims to review
      the literature on occupational groups at risk of voice disorders and identify
      areas for future research. METHOD: A literature review of key databases using key
      words such as 'occupational', 'voice health', 'voice loss', 'dysphonia' and 'work
      related' was undertaken. RESULTS: The review identified case reports, studies of
      attendees at hospital voice clinics and a few cross-sectional studies of
      occupational groups in the workplace. There were no longitudinal studies found or
      intervention studies looking at reduction of risk. CONCLUSION: Further research
      on occupational voice disorders needs to be based in the workplace, and to look
      at the risk factors for the development of voice problems and for the efficacy of
      controls.

PMID- 14581644
TI  - Sick leave analysis among self-employed Dutch farmers.
AB  - BACKGROUND: Agriculture is one of the most physically demanding and risky
      industries. Aim The objective of this study was to provide baseline data on the
      diagnoses, occurrence and duration of sick leave of self-employed Dutch farmers.
      METHOD: A database of 22 807 sick leave claims of 12 627 farmers during the
      period 1994-2001 was analysed. RESULTS: Most of the claims (61%) were for musculo
      skeletal injuries and disorders. The mean cumulative incidence (CI) was 10.2
      claims per year per 100 farmers and did not change over time. However, it varied
      per agricultural sector and per age category, being lowest in arable farming and
      in the youngest age category and highest in mushroom farming and in the oldest
      age category. The duration of sick leave depended both on diagnosis and age
      category: the slowest recovery from sick leave was seen in farmers with
      respiratory diseases and farmers in the oldest age category. CONCLUSION: The
      results make it easier to identify groups of farmers to be targeted to prevent
      sick leave. To reduce the occurrence of sick leave in agriculture, the strategy
      should be to prevent musculo-skeletal injuries and disorders. Furthermore, a
      sector-specific approach is recommended, so that preventive actions can be
      focused on working conditions-specifically on workload and work safety. Efforts
      to shorten the duration of sick leave will also be valuable to obtain a reduction
      of sick leave.

PMID- 14581645
TI  - Peer-group risk assessment: a post-traumatic management strategy for hierarchical
      organizations.
AB  - BACKGROUND: Organizations have moral and legal duties to consider the
      psychological needs of their workforce following exposure to potentially
      traumatic events related to the workplace. Additionally, it makes economic sense
      to avoid loss of valuable personnel to the effects of psychological trauma. There
      have been attempts to provide a range of psychological interventions for staff
      after exposure to potentially traumatizing events, but recent evidence-based
      medicine publications have questioned their effectiveness and, indeed, some
      studies show that single-session psychological debriefings may be harmful. AIM:
      This paper presents a post-traumatic management strategy based upon peer-group
      risk assessment which was developed by the British military and is in use with
      other hierarchical organizations. The presented model keeps employees functioning
      after traumatic events and provides support and education to those who require
      it. Additionally, the strategy aims to identify those who are unable to cope
      after potentially traumatizing events and aims to refer them for early
      intervention, which has been shown to be of benefit.

PMID- 14581646
TI  - Chronic lead poisoning in an adult battery worker.
AB  - BACKGROUND: Lead poisoning is a common environmental health hazard in developing
      countries. Incidences of lead poisoning are seen in all age groups, especially in
      adults working in lead-based industries, where many still remain unaware of the
      adverse effects of exposure to unusually high levels of lead. METHODS: We report
      the case of an adult battery worker, who initially received symptomatic treatment
      because of clinical misdiagnosis. Later, he was treated with appropriate
      chelators, which helped to decrease blood lead levels drastically. However, being
      unable to change his occupation, he continues to be exposed to potentially lethal
      doses of lead. CONCLUSIONS: A key role for health agencies, besides providing
      opportunities for diagnosis and therapy, should be to increase public awareness
      about this widespread environmental hazard through education, documentation and
      communication.

PMID- 14581647
TI  - Central neurological abnormalities and multiple chemical sensitivity caused by
      chronic toluene exposure.
AB  - Multiple chemical sensitivity (MCS) is a syndrome in which multiple symptoms
      occur with low-level chemical exposure; whether it is an organic disease
      initiated by environmental exposure or a psychological disorder is still
      controversial. We report a 38-year-old male worker with chronic toluene exposure
      who developed symptoms such as palpitation, insomnia, dizziness with headache,
      memory impairment, euphoria while working, and depression during the weekend.
      Upon cessation of exposure, follow-up neurobehavioural tests, including the
      cognitive ability screening instrument and the mini-mental state examination,
      gradually improved and eventually became normal. Although no further toluene
      exposure was noted, non-specific symptoms reappeared whenever the subject smelled
      automotive exhaust fumes or paint, or visited a petrol station, followed by
      anxiety with sleep disturbance. During hospitalization for a toluene provocation
      test, there was no difference between pre-challenge and post-challenge PaCO(2),
      PaO(2), SaO(2) or pulmonary function tests, except some elevation of pulse rate.
      The clinical manifestations suggested that MCS was more relevant to
      psychophysiological than pathophysiological factors.

PMID- 14581648
TI  - Microorganism-induced skin disease in workers exposed to metalworking fluids.

PMID- 14581650
TI  - Microorganism-induced skin disease in workers exposed to metalworking fluids.

PMID- 14581651
TI  - Monitor.

PMID- 14581652
TI  - Contemporary concepts of migraine pathogenesis.
AB  - The pathogenesis of migraine is incompletely understood. Recent discoveries have
      shed light on the neuronal events mediating both the aura and the headache phases
      of migraine, identifying a cerebral cortical origin of migraine aura,
      susceptibility to attacks based on cortical hyperexcitability, and headache
      originating in the trigeminovascular system and its central projections. Abnormal
      modulation of brain nociceptive systems, at first transient but becoming
      permanent with continuing illness and, predisposing to central sensitization, may
      explain the prolonged headache of the migraine attack and the shift of the
      migraine phenotype from episodic to chronic headache. Migraine attacks might also
      originate in abnormal nociceptive neuromodulator centers in the brainstem.

PMID- 14581654
TI  - Treatment approaches to maximizing therapeutic response in migraine.
AB  - Migraine is a chronic condition that presents with episodic disabling attacks,
      which can respond unpredictably to therapies. Studies support early treatment
      intervention strategies as part of the routine clinical care of migraine
      patients. Identifying illness severity and stratifying treatment accordingly (as
      in other diseases such as asthma, diabetes, or hypertension) improves patient
      outcome. Assessing the presence of any coexisting conditions, such as depression
      or anxiety, is another essential part of managing migraine.

PMID- 14581653
TI  - Therapeutic implications of central and peripheral neurologic mechanisms in
      migraine.

PMID- 14581655
TI  - Zolmitriptan nasal spray: advances in migraine treatment.
AB  - Zolmitriptan nasal spray was developed specifically to achieve fast, high
      effectiveness and to overcome many of the limitations associated with oral and sc
      migraine therapies. Pharmacokinetic studies have demonstrated a very rapid
      appearance of zolmitriptan in plasma as early as 5 minutes after intranasal
      dosing, with about 40% of peak plasma concentration (C(max)) being achieved
      within 10 to 15 minutes of dosing. Comparison of plasma concentration-time
      profiles of zolmitriptan and its active metabolite after oral and intranasal
      administration, together with PET scanning, clearly indicate direct absorption of
      zolmitriptan across the nasal mucosa after intranasal administration. The
      remainder of the dose is then swallowed and is absorbed through the
      gastrointestinal tract. In one blinded, randomized, placebo-controlled, multiple
      attack study of zolmitriptan nasal spray, headache response was superior to
      placebo as early as 15 minutes after dosing (p < 0.05). In the zolmitriptan 5 mg
      treatment group, the primary end point of 2-hour headache response was achieved
      in 70% (300/427) of attacks versus 31% of attacks (119/389 attacks) in the
      placebo group (p < 0.001). Patients achieved a 2-hour headache response, had no
      recurrence, and used no additional or escape medications for up to 24 hours in
      49% of attacks versus 14% of attacks in the placebo group (p < 0.001).
      Zolmitriptan 5 mg nasal spray was well tolerated. These data and those from other
      similar studies demonstrate that zolmitriptan nasal spray combines early,
      sustained efficacy and good tolerability, making it an optimal acute treatment
      for migraine.

PMID- 14581656
TI  - Clinical applications of new therapeutic deliveries in migraine.
AB  - A number of serotonin (5-HT)1B/1D agonists (triptans) are available worldwide for
      the treatment of migraine. The first-generation triptan, sumatriptan, was
      initially launched as an SC injection, which is fast-acting and consistently
      effective but relatively expensive and can be associated with adverse events in
      some patients. Sumatriptan was then launched as an oral tablet, shortly followed
      by the development of second-generation triptans that are now available in
      several formulations. Tablets are highly effective and convenient but may not be
      suitable in all migraine situations, e.g., migraine-associated nausea or vomiting
      and gastric disturbances. An intranasal route of administration appears to be an
      obvious way to deliver a migraine treatment and two triptans, sumatriptan and
      zolmitriptan, are available in nasal spray formulations. Sumatriptan offered the
      first nasal spray and has similar efficacy to the sumatriptan tablet, but the
      response is inconsistent and many patients cannot tolerate the unpleasant taste.
      The latest nasal spray, zolmitriptan, has produced exciting results in clinical
      studies and combines a rapid onset of action and consistently high response rates
      with a good tolerability profile. Early results from the author's clinic suggest
      that this promise is realized in clinical practice and that this combination of
      patient benefits makes zolmitriptan nasal spray an ideal way for patients to
      treat their migraine. With the introduction of zolmitriptan nasal spray,
      zolmitriptan is now available in three different formulations, enabling patients
      to tailor their treatment to the circumstances of the individual attack.

PMID- 14581657
TI  - Blood pressure reduction in ischemic stroke: a two-edged sword?

PMID- 14581658
TI  - Environmental risk factors in multiple sclerosis: causes, triggers, and patient
      autonomy.

PMID- 14581659
TI  - Nonconvulsive status epilepticus.

PMID- 14581660
TI  - The medial brachial fascial compartment syndrome following axillary
      arteriography.
AB  - OBJECTIVE: To review clinical and electrodiagnostic features of the medial
      brachial fascial compartment syndrome, a complication of percutaneous axillary
      vessel puncture. METHODS: The authors reviewed electrodiagnostic examinations
      over a 20-year period. RESULTS: This syndrome presents with weakness, pain, and
      numbness during or following the percutaneous procedure. Injury is characterized
      by axon loss and involves terminal nerves of the infraclavicular brachial plexus
      most often the median nerve alone, followed by combinations of the median, ulnar,
      radial, and musculocutaneous nerves. CONCLUSIONS: Early recognition of the medial
      brachial fascial compartment syndrome may lead to prompt surgical intervention,
      which, in turn, may prevent permanent nerve injury. Late diagnosis generally
      results in poor outcome and often results from delayed symptom onset and lack of
      overt compartment syndrome signs.

PMID- 14581661
TI  - Mosaic mutations of the LIS1 gene cause subcortical band heterotopia.
AB  - BACKGROUND: Subcortical band heterotopia (SBH) is a neuronal migration disorder.
      DCX mutations are responsible for almost all familial cases, 80% of sporadic
      female cases, and 25% of sporadic male cases of SBH, and are associated with more
      severe gyral and migration abnormality over the anterior brain regions. Somatic
      mosaicism has previously been hypothesized in a patient with posteriorly
      predominant SBH and a mutation of the LIS1 gene, which is usually mutated in
      patients with severe lissencephaly. The authors identified mosaic mutations of
      LIS1 in two patients (Patients 1 and 2) with predominantly posterior SBH.
      METHODS: After ruling out DCX mutations, the authors performed sequencing of the
      LIS1 gene in lymphocyte DNA. Because sequence peaks in both patients were
      suggestive of mosaic mutations, they followed up with denaturing high-pressure
      liquid chromatography analysis on blood and hair root DNA and compared the areas
      of heteroduplex and homoduplex peaks. A third patient showing the same mutation
      as Patient 2 but with no evidence of mosaicism was used for comparing the
      phenotype of mosaic vs full mutation. RESULTS: The two patients with posterior
      SBH harbored a missense (Arg241Pro) and a nonsense (R8X) mosaic mutation of LIS1.
      The rate of mosaicism in Patient 1 was 18% in the blood and 21% in the hair
      roots, whereas in Patient 2 it was 24% and 31% in the same tissues. The patient
      with a full R8X mutation of LIS1 had severe lissencephaly. CONCLUSIONS:
      Subcortical band heterotopia can occur with mosaic mutations of the LIS1 gene.
      Mutation analysis of LIS1, using highly sensitive techniques such as denaturing
      high-pressure liquid chromatography, should be considered for patients with
      posteriorly predominant subcortical band heterotopia and pachygyria.

PMID- 14581662
TI  - Detrimental effect of blood pressure reduction in the first 24 hours of acute
      stroke onset.
AB  - BACKGROUND: High blood pressure, although the main modifiable risk factor for
      stroke, may have a beneficial effect in maintaining brain perfusion after acute
      ischemia. The authors assessed the effects of blood pressure variation in the
      first 24 hours of stroke onset. METHODS: The authors prospectively studied
      consecutive patients admitted in the first 24 hours after stroke onset. Patients
      were classified according to the NIH Stroke Scale (NIHSS) and Oxfordshire Stroke
      Classification Scale (OSCS). Stroke etiology was defined according to Trial of
      ORG 10172 in Acute Stroke Treatment classification. After 3 months, outcome was
      assessed using Rankin and Barthel scales, with poor outcome defined as Rankin
      score > 2 or Barthel score < 70. RESULTS: A total of 115 patients were admitted
      between January 2001 and October 2002. Median NIHSS was 4.5; main stroke etiology
      was cardioembolism (30%). After 3 months, 44 (39%) patients had a poor outcome.
      Predictors of poor outcome in univariable analyses (p < 0.05) were as follows:
      total anterior circulation classification on OSCS, nonlacunar stroke etiology,
      older age, higher NIHSS score, lack of antiplatelet use, higher body temperature,
      lower diastolic blood pressure on admission, and a larger degree of systolic
      blood pressure reduction. In the multivariable analysis, remaining predictors of
      poor outcome included the following: NIHSS score (OR = 1.55 per 1 point increase;
      95% CI = 1.28 to 1.87; p < 0.001) and degree of systolic blood pressure reduction
      in the first 24 hours (OR = 1.89 per 10% decrease; 95% CI = 1.02 to 3.52; p =
      0.047). CONCLUSION: Blood pressure reduction in the first 24 hours of stroke
      onset is independently associated with poor outcome after 3 months.

PMID- 14581663
TI  - Prognostic value of Pulsatility Index in acute intracerebral hemorrhage.
AB  - OBJECTIVE: To investigate whether data obtained by transcranial Doppler (TCD)
      have prognostic value in patients with intracerebral hemorrhage (ICH). METHODS: A
      prospective study of patients with an acute (<12 hours from onset of symptoms)
      spontaneous supratentorial ICH was conducted. Mortality was assessed at 30-day
      follow-up. TCD parameters were obtained from both middle cerebral arteries:
      systolic, diastolic, and mean velocities and Pulsatility Index (PI) from the
      affected and unaffected hemispheres. The following variables were included in a
      univariate analysis: age, sex, hematoma volume, hypodense volume around the
      hematoma, total volume, midline shift, ventricular size, Glasgow Coma Scale
      score, intraventricular hemorrhage, body temperature, white cell count, blood
      glucose, mean blood pressure, and TCD data. A multivariate analysis was performed
      with variables that showed significance in the univariate analysis. Receiver
      operator characteristic (ROC) curves were obtained. RESULTS: Forty-eight patients
      (age 66.5 +/- 12.5 years; 28 men) were studied. Mortality at 30 days was 31%. The
      only predictor of mortality was the Glasgow Coma Scale score (odds ratio [OR]
      0.67, CI 0.53 to 0.84, p = 0.001), whereas the PI from the unaffected hemisphere
      was correlated with mortality (OR 2.3, CI 0.92 to 5.72, p = 0.07). The area under
      the ROC curve was 0.92. A cutoff for PI from the unaffected hemisphere of 1.75
      showed a specificity of 94% and a sensitivity of 80% as a predictor of death at
      30 days. CONCLUSIONS: The PI of the unaffected hemisphere may be a predictor of
      death in acute ICH. These findings suggest that intracranial hypertension is the
      most likely cause of death in most patients with ICH.

PMID- 14581664
TI  - Is measurement of D-dimer useful in the diagnosis of cerebral venous thrombosis?
AB  - BACKGROUND: The diagnosis of cerebral venous thrombosis (CVT) is a challenge
      because its clinical presentation is variable, brain CT may be normal, and MRI is
      not always available. Furthermore, early treatment may be effective. As D-dimer
      (DD) measurement is a sensitive test for the exclusion of venous thromboembolism,
      the authors studied whether this test could be useful in the diagnosis of CVT.
      METHODS: A prospective study of 54 consecutive patients with headaches suggestive
      of CVT was conducted between October 2000 and September 2002. DD levels were
      tested for all patients in the emergency room before brain CT or MRI was
      performed. RESULTS: Twelve (22%) of the 54 patients had CVT, and 10 (83%) of
      these 12 patients had DD level of >500 ng/mL (sensitivity of 83% and negative
      predictive value of 95%). Two patients with confirmed CVT and DD of <500 ng/mL
      had a history of chronic headache of >30 days' duration. In the 42 patients
      without confirmed CVT, only 4 patients had DD level of >500 ng/mL (specificity of
      90% and positive predictive value of 71%). CONCLUSIONS: DD test is useful in the
      diagnosis of acute CVT. A value below 500 ng/mL makes acute thrombosis unlikely.

PMID- 14581665
TI  - Brain diffusion changes in carotid occlusive disease treated with endarterectomy.
AB  - BACKGROUND: Patients with unilateral high-grade carotid stenosis or occlusion
      have been reported to have more leukoaraiosis and ischemic lesions in ipsilateral
      than in contralateral cerebral hemisphere. The lesions alter apparent diffusion
      coefficient (ADC) values in diffusion-weighted MRI (DWI). The overall effects of
      carotid endarterectomy on ADC values have not yet been explored. OBJECTIVE: S: To
      find out whether 1) average ADC (ADC(av)) values differed between hemispheres, 2)
      diffusion changes induced by carotid endarterectomy could be detected in brain
      tissue with serial DWI, and 3) patients with asymptomatic carotid stenosis
      differed from patients with a symptomatic stenosis. METHODS: Forty-five patients
      (22 with asymptomatic carotid stenosis and 23 with symptomatic carotid stenosis)
      with unilateral high-grade carotid stenosis underwent DWI before carotid
      endarterectomy and 3 and 100 days afterward, and 45 age- and sex-matched healthy
      control subjects were imaged once. We evaluated ADC(av) values in normal
      appearing gray and white matter, watershed regions (WsR), and thalamus. RESULTS:
      ADC(av) values of ipsilateral white matter and WsR were higher than those of
      contralateral white matter and WsR, both being higher than in white matter and
      WsR of control subjects. After carotid endarterectomy, these differences were
      diminished, but the levels remained higher than in controls. ADC(av) values of
      gray matter and thalamus remained unaffected. Asymptomatic carotid stenosis and
      symptomatic carotid stenosis patient groups did not differ from each other.
      CONCLUSIONS: Carotid stenosis has an effect on diffusion in the white matter of
      the ipsilateral hemisphere, and it is partly reversible by carotid
      endarterectomy. The finding may be associated with leukoaraiotic development
      ("preleukoaraiosis").

PMID- 14581666
TI  - Assessment of acute morbidity and mortality in nonconvulsive status epilepticus.
AB  - OBJECTIVE: S: The natural history of nonconvulsive status epilepticus (NCSE) is
      not well defined, especially mortality and morbidity. The authors hypothesized
      that the mortality of NCSE is higher when NCSE is due to acute medical causes
      (systemic or neurologic) or associated with severe impairment of mental status or
      with acute complications, and lower when associated with generalized spike-wave
      (SW) discharges on EEG. METHODS: The authors retrospectively identified 100
      consecutive patients with NCSE from an EEG database. Data were collected from
      systematic review of medical records and actual EEG tracings. Specific etiologies
      were divided into three groups: acute medical, epilepsy, and cryptogenic.
      RESULTS: Of the 100 patients, 18 died. Fourteen of 52 patients in the acute
      medical group died, 1 of 31 in the epilepsy group died, and 3 of 17 in the
      cryptogenic group died. Mental status impairment was severe in 33, complications
      occurred in 39, and generalized SW discharges occurred in 36. Mortality rates
      were higher in patients 1) in the acute medical group (27%) vs the epilepsy (3%)
      and the cryptogenic (18%) groups (p < 0.02), 2) with severe mental status
      impairment (39%) compared to those with mild impairment (7%, p < 0.001), and 3)
      with acute complications (36%) when compared with those without complications
      (7%, p < 0.0002). The presence of generalized SW discharges on EEG did not
      correlate with mortality. Mental status impairment and etiology were
      independently associated with mortality (p < 0.001). CONCLUSION: NCSE is
      associated with substantial mortality. Mortality is associated with an acute
      medical cause as the underlying etiology, severe mental status impairment, and
      development of acute complications, but not the type of EEG discharge.

PMID- 14581667
TI  - Sevoflurane is epileptogenic in healthy subjects at surgical levels of
      anesthesia.
AB  - OBJECTIVE: To investigate EEG effects of three escalating concentrations of
      sevoflurane and propofol in single-agent anesthesia on healthy subjects. METHODS:
      Four-channel EEG was continuously recorded at 1, 1.5, and 2 minimum alveolar
      concentration (MAC)/effective plasma concentration 50 (EC50) levels of either
      sevoflurane or propofol anesthesia in 16 men, 8 subjects in each group. Each
      concentration level lasted for 30 minutes. EEG was first visually analyzed. In
      quantitative EEG analysis, the 95% spectral edge frequency (SEF95) and peak
      frequency (PF) were determined after fast Fourier transformation. RESULTS:
      Epileptiform discharges occurred in all eight subjects at 1.5 and 2 MAC levels of
      sevoflurane anesthesia. Three subjects showed electrographic seizures at 2 MAC
      level, in one case accompanied with clinical seizures despite muscle relaxation.
      Propofol did not produce remarkable epileptiform EEG phenomena at any level of
      anesthesia. Suppression and slowing of EEG activity were evident for both drugs
      with increasing concentration. Owing to the high incidence of epileptiform events
      in the sevoflurane group at 1.5 and 2 MAC, the SEF95 and PF values were higher (p
      < 0.001) compared with propofol. Within the sevoflurane group, these values were
      higher at the 2 than at the 1.5 MAC level (p values ranged between <0.001 and
      0.019). CONCLUSIONS: Sevoflurane consistently produces epileptiform discharges
      and is dose dependently epileptogenic at surgical levels of anesthesia.

PMID- 14581668
TI  - Cord damage elicits brain functional reorganization after a single episode of
      myelitis.
AB  - OBJECTIVE: To assess, using fMRI, the brain pattern of movement-associated
      cortical activations in patients with a previous remitting episode of acute
      cervical myelitis of possible demyelinating origin and to investigate whether the
      extent of cortical reorganization is associated with the extent of cervical cord
      pathology measured using magnetization transfer (MT) MRI. METHODS: From 14 right
      handed patients in a chronic and stable phase after an isolated myelitis
      (male/female = 7/7, mean age = 35.3 years, median disease duration = 21.2 months)
      involving the cervical cord and 15 sex- and age-matched healthy control subjects,
      we obtained 1) fMRI during repetitive flexion-extension of the last four fingers
      of the right hand, 2) brain diffusion tensor MRI, and 3) brain and cervical cord
      conventional and MT MRI. FMRI data were analyzed using Statistical Parametric
      Mapping software. Brain mean diffusivity, fractional anisotropy, and MT ratio
      (MTR) histograms of the normal-appearing white and gray matter and cervical cord
      MTR histograms were produced. RESULTS: Patients with myelitis had lower average
      cord MTR (p < 0.0001) and cord MTR histogram peak position (p = 0.002) than
      control subjects. Compared with healthy volunteers, patients with myelitis showed
      increased recruitment of the ipsilateral hemisphere in the primary sensorimotor
      cortex (p < 0.0001), supplementary motor area (p = 0.002), and middle frontal
      gyrus (MFG) (p < 0.0001). Average cervical cord MTR was inversely correlated with
      relative activations of the ipsilateral MFG (r = -0.80) and of the ipsilateral
      postcentral gyrus (r = -0.80). The relative activation of the ipsilateral MFG was
      also correlated with cervical cord MTR peak position (r = -0.92). CONCLUSIONS: An
      abnormal pattern of movement-associated cortical activations was found in
      patients with a previous episode of cervical myelitis. These functional cortical
      changes might have an adaptive role in limiting the clinical outcome of
      structural cord damage.

PMID- 14581669
TI  - Huntington's disease: clinical correlates of disability and progression.
AB  - OBJECTIVE: To define the phenotypic variation in a large population of patients
      with Huntington disease (HD) and to identity clinical features that predict
      disability and the rate of disease progression. METHODS: The authors analyzed
      data on 1,026 patients, followed for a median of 2.7 years, using a mixed effects
      model. The factors studied included the age at onset, the major clinical feature
      at onset, the severity of motor and cognitive impairment, and the level of
      disability. RESULTS: The mean age at onset was 41.5 (range 8 to 83) years, and
      patients were enrolled at all stages of disease. Younger onset was associated
      with more dystonia, less chorea, and a faster rate of motor, cognitive, and
      functional progression. The rate of progression was not related to the major
      clinical feature at onset or the sex of the affected parent. Disability
      correlated with the motor score (excluding chorea and dystonia) and the symbol
      digit modalities test. Weight loss correlated with severe chorea. CONCLUSIONS:
      The rate of progression of HD was significantly more rapid with a younger age at
      onset. Therefore, CAG repeat length may be an important determinant of not only
      the age at onset, but also the rate of disease progression. Chorea was associated
      with weight loss, but chorea and dystonia were not major determinants of
      disability.

PMID- 14581670
TI  - Hearing impairment in essential tremor.
AB  - OBJECTIVE: To assess hearing in patients with essential tremor (ET) vs patients
      with Parkinson disease (PD) and normal controls. METHODS: The authors assessed
      demographic and clinical information including use of hearing aids in 250
      patients with ET, 127 patients with PD, and 127 normal controls. The authors
      administered the Nursing Home Hearing Handicap Index (NHHI), a validated measure
      of hearing disability. Regression techniques were used to adjust for factors such
      as age and sex. The authors assessed a complete audiologic evaluation in a subset
      of patients with ET. RESULTS: Patients with ET had worse adjusted NHHI scores
      when compared to patients with PD (p < 0.001), controls (p < 0.001), and both (p
      < 0.001). A higher percentage of patients with ET also used hearing aids (p <
      0.0001). In the ET group, hearing loss was associated with tremor severity (p =
      0.02) and tended to be associated with older age (p = 0.06), male sex (p = 0.06),
      and the absence of dystonia (p = 0.18). Audiology testing was consistent with
      high-frequency sensorineural hearing loss. Central processing was not
      disproportionally greater than peripheral loss. CONCLUSION: Patients with ET have
      increased hearing disability compared to patients with PD and normal controls,
      which correlates with tremor severity.

PMID- 14581671
TI  - Candidate gene studies in focal dystonia.
AB  - BACKGROUND: Genetic susceptibility factors for focal idiopathic torsion dystonia
      (F-ITD) are not established. Mutations in the DYT1 gene can cause focal dystonia,
      and an association with a polymorphism in the D5 receptor gene (DRD5) has been
      reported but not confirmed. OBJECTIVE: To investigate a possible role of DYT1
      polymorphisms, a CA repeat in the D5 receptor gene (DRD5), the human leukocyte
      antigen (HLA)-DRB locus, and four polymorphisms in the homocysteine metabolism in
      the pathogenesis of F-ITD. METHODS: Initially, 100 German patients and 100
      matched control subjects were investigated. A second French population with 121 F
      ITD patients and matched control subjects was also studied. RESULTS: Two
      polymorphisms of the beta-cystathionine synthase gene were associated with F-ITD
      in the German population, but this finding was not replicated in a second
      independent F-ITD patient and control group of French origin. None of the other
      investigated polymorphisms was associated with F-ITD. The authors failed to
      confirm a previously reported association with a polymorphism in DRD5.
      CONCLUSION: No evidence for an involvement of DYT1, DRD5, HLA-DRB, or
      polymorphisms in the homocysteine pathway in the pathogenesis of F-ITD was found.

PMID- 14581672
TI  - Depressive symptoms, clinical AD, and cortical plaques and tangles in older
      persons.
AB  - BACKGROUND: Depressive symptoms in old age have been associated with risk of
      Alzheimer disease (AD), but it is uncertain whether they are an independent risk
      factor for disease or an early clinical sign of its underlying pathology.
      METHODS: A group of 130 older Catholic nuns, priests, and brothers underwent
      detailed annual clinical evaluations and brain autopsy at death. The evaluations
      included administration of a modified 10-item Center for Epidemiologic Studies
      Depression Scale (CES-D) and 19 cognitive performance tests and clinical
      classification of dementia and AD. On postmortem examination, neuritic plaques,
      diffuse plaques, and neurofibrillary tangles in tissue samples from four cortical
      regions were counted, and a previously established composite measure of cortical
      plaque and tangle density (range 0 to 2.98) was derived. All analyses were
      adjusted for age, sex, and education. RESULTS: Participants reported a mean 1.5
      depressive symptoms (SD 1.6) on the CES-D scale averaged across evaluations. In a
      logistic regression model, the odds of clinically diagnosed AD proximate to death
      increased by 1.33 (95% CI 1.01 to 1.76) for each depressive symptom and by 8.41
      (95% CI 3.49 to 20.26) for each unit on the composite measure of pathology. In
      subsequent analyses, depressive symptoms were not related to level of pathology
      and did not modify the relation of pathology to clinical AD. In a series of
      linear regression models that controlled for pathology, depressive symptoms were
      related to level of cognitive function proximate to death and did not modify the
      association of pathology with cognition. CONCLUSION: The association of
      depressive symptoms with clinical AD and cognitive impairment appears to be
      independent of cortical plaques and tangles.

PMID- 14581673
TI  - Speech and language in progressive nonfluent aphasia compared with early
      Alzheimer's disease.
AB  - BACKGROUND: Progressive nonfluent aphasia (PA) is a slow deterioration of
      language that remains relatively isolated from other cognitive or behavioral
      deficits for at least 2 years. The differentiation of PA from early Alzheimer's
      disease (AD) is important, given the presence of early language changes in AD.
      METHODS: A language assessment was administered to 15 patients who met
      established criteria for PA, 15 patients with clinically probable AD and mild
      dementia, and 15 normal control subjects. The language battery included verbal
      fluency, the Boston Naming Test with cuing and recognition, and an aphasia test
      battery with a motor speech exam. RESULTS: Pronounced literal paraphasic errors
      distinguished the PA patients from the AD patients. The PA group had anomia,
      decreased letter fluency, neologisms, difficulty on phrase repetition, decreased
      phrase length, and a decreased rate of verbal output. Interference from
      paraphasic anomia accounted for much of their decreased fluency. CONCLUSION: Many
      patients with PA have a primary defect in accessing sound-based representation of
      speech (phonemes), similar to conduction aphasia, possibly as a consequence of
      disturbed white matter tracts in the left superior temporal region.

PMID- 14581674
TI  - Glutamate uptake by oligodendrocytes: Implications for excitotoxicity in multiple
      sclerosis.
AB  - BACKGROUND: Excitotoxic damage is a common pathologic event in a number of
      neurologic diseases occurring after accumulation of excess extracellular
      glutamate in the CNS and subsequent overstimulation of glutamate receptors. In
      gray matter, astrocytes take up synaptically released glutamate and are thus key
      cells in maintaining glutamate homeostasis. In white matter, oligodendrocytes
      have been shown to express glutamate transporters, but their role in
      extracellular glutamate removal is unclear. OBJECTIVE: To investigate whether
      cultured human fetal oligodendrocytes functionally express the main glutamate
      transporters EAAT-1 and EAAT-2. METHODS: Cultures of fetal human oligodendrocytes
      were examined by immunocytochemistry and [3H]glutamate uptake, and the findings
      were correlated with glutamate transporter expression in normal and multiple
      sclerosis (MS) CNS tissue. RESULTS: Both EAAT-1 and EAAT-2 were expressed by
      human oligodendrocytes in vitro. Incubation of oligodendrocytes with the
      proinflammatory cytokine tumor necrosis factor-alpha (TNFalpha) reduced EAAT-1
      expression and inhibited glutamate uptake by >75%. Furthermore, in normal human
      white matter, oligodendrocytes were found to be the predominant cells to express
      EAAT-1 and EAAT-2, both at the mRNA and at the protein level. A small number of
      astrocytes in white matter expressed these receptors, more so EAAT-1 than EAAT-2.
      In MS white matter, oligodendrocytes lost expression of EAAT-1 and EAAT-2
      receptors in the lesion vicinity. CONCLUSIONS: Oligodendrocytes appear to be
      predominant cells for glutamate clearance in human white matter. Glutamate
      receptor expression and glutamate removal were defective in MS white matter,
      possibly mediated by TNFalpha, changes that might underlie high extracellular
      glutamate and an increased risk for glutamate excitotoxicity.

PMID- 14581675
TI  - Lingual atrophy and dolichoectatic artery.

PMID- 14581676
TI  - Smoking is a risk factor for multiple sclerosis.
AB  - The authors determined the relationship between tobacco smoking and the risk of
      developing multiple sclerosis (MS) in a general population of 22,312 individuals
      living in Hordaland, Norway in 1997. A total of 87 individuals reported having
      developed MS. The risk of MS was higher among smokers than among never-smokers
      (rate ratio 1.81, 95% CI 1.1 to 2.9; p = 0.014). Studies on how smoking interacts
      with disease onset may contribute to determining the causal agents of this
      disease.

PMID- 14581677
TI  - Hashimoto's encephalopathy: postmortem findings after fatal status epilepticus.
AB  - The clinical features of Hashimoto's encephalopathy have been attributed to a
      cerebral vasculitis, but pathologic material is rarely available. The authors
      describe an individual with Hashimoto's encephalopathy complicated by fatal
      status epilepticus. Postmortem examination demonstrated mild perivascular
      lymphocytic infiltration throughout the brain and leptomeninges plus diffuse
      gliosis of gray matter in the cortex, basal ganglia, thalami, hippocampi, and, to
      a lesser extent, the parenchymal white matter.

PMID- 14581678
TI  - Sleep apnea and excessive daytime somnolence induced by vagal nerve stimulation.
AB  - Vagal nerve stimulation (VNS) therapy affects respiration during sleep and can
      interrupt sleep. VNS has also been noted to improve excessive daytime sleepiness.
      The authors present a patient who developed excessive daytime sleepiness after
      VNS placement, as a consequence of apneas and arousals associated with
      intermittent electrical stimulation of the left vagus nerve.

PMID- 14581679
TI  - Atypical BECTS and homocystinuria.
AB  - Reported is an association of atypical benign childhood epilepsy with
      centrotemporal spikes (BECTS) and homocystinuria in three apparently healthy
      children with borderline intelligence, two of whom had difficult-to-control
      seizures. In all three, EEG were suggestive of BECTS, although the clinical
      features were not. Homocystinuria could not be diagnosed for several years,
      pending metabolic evaluation.

PMID- 14581680
TI  - Glucose levels and outcome after subarachnoid hemorrhage.
AB  - In a cohort of 337 patients with subarachnoid hemorrhage (SAH), we investigated
      the relationship between blood glucose levels, baseline characteristics, and
      outcome by means of Student's t-test and multivariate logistic regression. The
      mean glucose levels on admission and from day 1 to 10 were significantly higher
      in patients with poor condition on admission and in patients with poor outcome.
      In a multivariate analysis, glucose level on admission was not an independent
      predictor of outcome. Hyperglycemia may be a link in the association between poor
      condition on admission and poor outcome.

PMID- 14581681
TI  - Pathologically confirmed corticobasal degeneration presenting with visuospatial
      dysfunction.
AB  - Corticobasal degeneration (CBD) typically manifests as progressive asymmetric
      rigidity and apraxia, although other non-motor presentations have been reported.
      We report two patients with pathologically diagnosed CBD who presented with
      prominent visuospatial dysfunction. The pathological changes were maximal in the
      visual association cortices, but absent in 31 cases of pathologically proven CBD
      with more typical antemortem features. Underlying CBD should be considered in the
      differential diagnosis of patients with findings reflecting posterior cerebral
      dysfunction.

PMID- 14581682
TI  - Very early onset AD with a de novo mutation in the presenilin 1 gene (Met 233
      Leu).
AB  - The authors describe a 28-year-old woman with histopathologically confirmed early
      onset Alzheimer disease characterized by severe frontal lobe involvement
      associated with a de novo mutation in the presenilin 1 gene (PSEN1).

PMID- 14581683
TI  - Brain metabolic differences between sporadic and familial Alzheimer's disease.
AB  - This FDG-PET study with SPM99 compared 46 patients with sporadic Alzheimer
      disease (SAD) to 40 patients with familial AD (FAD) and to 35 matched controls.
      AD groups had equivalent metabolic (METglu) reductions in several cortical and
      limbic areas with respect to the controls. Patients with FAD showed decreased
      METglu in the posterior cingulate, parahippocampal, and occipital cortex as
      compared to the patients with SAD (p < 0.001). Genetic factors lead to phenotypic
      differences in AD.

PMID- 14581684
TI  - Riluzole serum concentrations in patients with ALS: associations with side
      effects and symptoms.
AB  - Riluzole exerts a dose-dependent effect on survival of patients with ALS and,
      although serum levels show a high interindividual variability, is usually
      prescribed in a fixed dose. In this study, riluzole serum levels and area under
      the curve per kilogram of body weight (AUC/kg) of 169 patients with ALS showed a
      high interindividual variability. Patients with high serum levels and AUC/kg more
      often had diarrhea but less often had fasciculations and muscle stiffness. It may
      therefore be advantageous to raise the riluzole dose in patients with low
      riluzole serum concentrations without the risk of serious side effects.

PMID- 14581685
TI  - Classical mitochondrial phenotypes without mtDNA mutations: the possible role of
      nuclear genes.
AB  - The authors analyzed the total mitochondrial (mt) genome in 15 patients with
      classic mitochondrial phenotypes. Novel somatic mtDNA mutations in two patients
      with chronic progressive external ophthalmoplegia were identified. Total
      automated mtDNA genome analysis did not reveal other pathogenic mtDNA mutations.
      The authors conclude that classic mitochondrial phenotypes, including those with
      adult onset, may occur in the absence of mtDNA mutations. Nuclear gene mutations
      may be the cause.

PMID- 14581686
TI  - Asymptomatic giant arachnoidal cyst.

PMID- 14581687
TI  - Aggressive confusional state as a clinical manifestation of status epilepticus in
      MELAS.

PMID- 14581688
TI  - Hypersensitivity pneumonitis possibly caused by riluzole therapy in ALS.

PMID- 14581689
TI  - Acute fatal stroke immediately following autologous fat injection into the face.

PMID- 14581690
TI  - Transient brainstem ischemia and recurrent syncope caused by a dural
      arteriovenous fistula.

PMID- 14581691
TI  - Conduction block of varicella zoster virus neuropathy.

PMID- 14581692
TI  - Hypoglossal neuropathy in hereditary neuropathy with liability to pressure palsy.

PMID- 14581693
TI  - Transient improvement of tardive dyskinesia induced with rTMS.

PMID- 14581695
TI  - Benign paroxysmal positional vertigo in Parkinson's disease.

PMID- 14581694
TI  - Intrathecal baclofen pump implantation during pregnancy.

PMID- 14581696
TI  - Successful treatment of hypnic headache syndrome with acetazolamide.

PMID- 14581697
TI  - Antiphospholipid-protein antibodies and acute ischemic stroke in the NINDS rt-PA
      Stroke Trial.

PMID- 14581698
TI  - Neuropsychiatric findings in anti-Ma2-positive paraneoplastic limbic
      encephalitis.

PMID- 14581699
TI  - Antiepileptic drug prophylaxis in severe traumatic brain injury.

PMID- 14581700
TI  - Mirtazapine induces REM sleep behavior disorder (RBD) in parkinsonism.

PMID- 14581701
TI  - Lyme disease and optic neuritis: long-term follow-up of seropositive patients.

PMID- 14581702
TI  - The prefaces of Charcot: leitmotifs of an international career.

PMID- 14581703
TI  - Patient page. Cigarette smoking and multiple sclerosis (MS): yet another reason
      to quit.

PMID- 14581705
TI  - The place where business logic meets outcomes.

PMID- 14581704
TI  - Plain talk about wound pain.

PMID- 14581706
TI  - Patient teaching: intestinal obstruction.

PMID- 14581707
TI  - Evaluation of two calcium alginate dressings in the management of venous ulcers.
AB  - Calcium alginate dressings facilitate the management of highly exudating wounds
      such as venous ulcers. To evaluate and compare the performance of two calcium
      alginate dressings in the management of venous ulcers, a prospective, randomized,
      controlled clinical study was conducted among 19 outpatients at two wound clinics
      in California. Ten patients (53%) were treated with Alginate A and nine patients
      (47%) with Alginate B. Dressings were changed weekly and patients were followed
      for a maximum of 6 weeks or until the venous ulcer no longer required the use of
      an alginate dressing. At each dressing change, the wound was assessed and
      dressing performance evaluated. Absorbency of exudate, patient comfort during
      wear, ease of removal, adherence to wound bed, dressing residue following initial
      irrigation, patient comfort during removal, ease of application, and
      conformability were assessed. Patients using Alginate A experienced significantly
      less foul odor (P = 0.02) and less denuded skin (P = 0.04) than Alginate B at
      follow-up wound assessments. With the exception of conformability, Alginate A was
      rated significantly better than Alginate B (P less than or equal to 0.05) in all
      dressing performance assessments. No significant healing differences were
      observed. As the different performance characteristics of various calcium
      alginate dressings become more obvious in clinical practice, further study is
      warranted to determine their optimal effectiveness.

PMID- 14581708
TI  - Preparing the wound for healing: the effect of activated polyacrylate dressing on
      debridement.
AB  - Activated polyacrylate dressings facilitate wound debridement by retaining
      moisture while attracting and retaining proteins and bacteria. A 55-patient
      retrospective study was conducted to quantify the effect of this dressing on
      debridement of chronic wounds in clinical practice. All patients attended one of
      four outpatient wound clinics between June 1, 2001 and February 10, 2002 and
      received treatment with the polyacrylate dressing for an average of 3.9 weeks (SD
      4.1). During that time, the rate of wound necrotic tissue debridement was 37.7%
      per week. Older patients (>80 years of age) had significantly lower rates of
      wound debridement (mean 18.1% per week) than those <51 years of age (mean 36% per
      week, P = 0.009). Other variables (age, wound type, wound duration and diagnosis
      of diabetes) were not found to significantly affect the rate of wound
      debridement. Wound debridement rates of commonly available modalities are largely
      unknown. However, these results suggest that activated polyacrylate dressings are
      an effective, atraumatic, and easy-to-use method of debriding chronic wounds.

PMID- 14581709
TI  - A study to compare a new self-adherent soft silicone dressing with a self
      adherent polymer dressing in stage II pressure ulcers.
AB  - Pressure ulcers are common among elderly nursing home residents. To be effective
      in managing these wounds, a dressing should maintain a moist environment,
      facilitate healing, absorb exudate, remain in place for a number of days, and
      prevent trauma to the surrounding skin. An 8-week, open, randomized, multicenter,
      controlled study was conducted to compare the effects of a new self-adherent soft
      silicone dressing and a self-adherent hydropolymer dressing on Stage II pressure
      ulcers. Thirty-eight (38) residents participated in the study. Eighteen residents
      (mean age 83.8 years, range 74.9 to 95.1 years) were randomized to wound
      management with a soft silicone dressing, and the ulcers of 20 residents (mean
      age 82.5 years, range 66.4 to 91.9 years) were managed with a hydropolymer
      dressing. Wound healing, wound and surrounding skin characteristics, and ease of
      dressing removal were measured and documented. During the study, eight (44%)
      ulcers in the soft silicone group and 10 (50%) in the hydropolymer dressing group
      healed. Both dressings were changed approximately once a week and no differences
      in signs of inflammation, amount of exudate and odor, or incidence of leakage
      were observed. Damage to the surrounding skin, maceration, and dressing removal
      difficulties were less common with the soft silicone dressing. Differences in
      tissue damage between the two dressings were significant during weeks 1, 2, and 3
      (P < 0.05). Studies with a larger sample size are needed to confirm these
      findings.

PMID- 14581710
TI  - Progress in pharmacotherapy of thrombosis.
AB  - Excessive coagulation and impaired fibrinolysis lead to many hemostatic
      disorders, which enhance the risk of development of life-threatening
      cardiovascular diseases such as myocardial infarction, stroke, deep venous
      thrombosis and pulmonary embolism, belonging to the most important factors
      influencing morbidity and mortality in civilized societies. The adverse events
      induced by currently used drugs, the need for regular monitoring of coagulation
      parameters, inconvenient, in some cases, route of administration stimulate
      further search for novel, effective and safe methods of therapies of these
      disorders. In this paper, we describe those new agents which are now under
      experimental and clinical study, such us prostanoids, nitroaspirin, GP IIb/IIIa
      receptor antagonists, thienopyridine derivatives, collagen-GPVI and von
      Willebrand factor-GPIb-IX contact blockers, direct thrombin inhibitors,
      inhibitors of thrombin-platelet interactions, factor VII inhibitors and tissue
      factor-factor VII contact blockers. Based on the available literature, we discuss
      the possible role of these agents in the future prevention and treatment of
      thromboembolic diseases.

PMID- 14581711
TI  - Is nitric oxide involved in the anticonvulsant action of antiepileptic drugs?
AB  - Experimental data indicate that nitric oxide (NO) may play a role in the
      pathophysiology of epilepsy. It is also possible that NO-mediated events are
      involved in the expression of the anticonvulsant action of some antiepileptics.
      The aim of this review was to assemble current literature data on the role of NO
      in the anticonvulsant action of antiepileptic drugs (AEDs). The influence of
      various NO synthase inhibitors (NOSI) on antiseizure activity of AEDs was tested
      in many animal experimental models of epilepsy (electrically and
      pharmacologically evoked seizures, sound-induced convulsions, amygdala-kindled
      seizures). Although some NOSI were able to modify the anticonvulsive properties
      of AEDs, the involvement of NO pathway in the mechanisms of action of AEDs in
      most cases does not seem probable, since the effects of NOSI were not reversed by
      L-arginine, a NO precursor.

PMID- 14581712
TI  - Novel 4-alkyl-1-arylpiperazines and 1,2,3,4-tetrahydroisoquinolines containing
      diphenylmethylamino or diphenylmethoxy fragment with differentiated 5-HT1A/5
      HT2A/D2 receptor activity.
AB  - Two series of 4-alkyl-1-arylpiperazines (1-4) and 1,2,3,4-tetrahydroiso
      quinolines (5, 6) with diphenylmethylamino (series a) or diphenylmethoxy (series
      b) fragment were synthesized in order to obtain potential ligands of 5-HT1A
      and/or 5-HT2A and dopamine D2 receptors. Four new arylpiperazines (1a, 3a, 1b,
      3b) were found to demonstrate high 5-HT1A receptor affinity (Ki = 1.5-35 nM);
      among them, 3a exhibited satisfactory 5-HT2A receptor affinity (Ki = 74 nM). Only
      compounds 1b and 2b showed moderate affinity for D2 receptor sites (Ki = 123 and
      128 nM, respectively). Compounds 1a, 3a, 1b and 3b were investigated in vivo to
      determine their functional activity at 5-HT1A receptors; additionally, 3a was
      tested for 5-HT2A receptor activity. Derivatives 1a, 1b and 3b produced effects
      characteristic of antagonists of postsynaptic 5-HT1A receptors. Moreover, 1b
      exhibited features of an agonist of presynaptic 5-HT1A receptors, while 3a
      behaved like a partial agonist of postsynaptic 5-HT1A sites. The latter
      derivative may also be classified as a 5-HT2A receptor antagonist. Thus, novel
      potent 5-HT1A receptor ligands were successfully obtained, and the most promising
      compound 3a showed mixed 5-HT1A/5-HT2A receptor activity in in vitro and in vivo
      tests.

PMID- 14581713
TI  - Synthesis and 5-HT1A/5-HT2A receptor activity of new N-[3-(4-phenylpiperazin-1
      yl)-propyl] derivatives of 3-spiro-cyclohexanepyrrolidine-2,5-dione and 3-spiro
      beta-tetralonepyrrolidine-2,5-dione.
AB  - Novel N-[3-(4-phenylpiperazin-1-yl)-propyl] derivatives of 3-spiro-cyclo
      hexanepyrrolidine-2,5-dione (5-7) and 3-spiro-beta-tetralonepyrrolidine-2,5-dione
      (8-10) were synthesized and their 5-HT1A and 5-HT2A receptor affinities were
      determined. All tested compounds exhibited moderate to low 5-HT1A receptor
      affinity, whereas compounds 5-7 demonstrated high 5-HT2A receptor affinity (Ki =
      27, 46 and 15 nM, respectively) and features of 5-HT2A receptor antagonists.
      Introduction of a beta-tetralone fragment in the 3-position of pyrrolidine-2,5
      dione ring (8-10) did not affect 5-HT1A but decreased 5-HT2A receptor affinity.

PMID- 14581714
TI  - Individual and combined effects of N6-cyclopentyladenosine, flunarizine and
      diazepam on aminophylline-induced recurrent generalized seizures in mice.
AB  - Protective effects of anticovulsant agents, N6-cyclopentyladenosine (CPA) and
      flunarizine (FLN) against aminophylline (AMPH) (280 mg/kg)-induced convulsions
      were tested in different groups of mice. All drugs were administered by
      intraperitoneal route. CPA (2 mg/kg and 4 mg/kg) delayed the time to onset of
      clonic convulsions (p < 0.05). The standard drug diazepam (DZP, 2.5 mg/kg)
      increased the time to onset of clonic and tonic convulsions to a statistically
      significant extent (p < 0.05 and p < 0.01, respectively). The AMPH-induced
      mortality (90.9%) was significantly reduced (p < 0.02) following the test
      anticonvulsants--CPA (2 mg/kg and 4 mg/kg), FLN (10 mg/kg) and the combination of
      CPA with FLN (though not to a significant extent), indicating partial involvement
      of adenosinergic and calcium related mechanisms, while DZP afforded maximum
      protection. However, none prevented the mortality in mice over 24 h. The results
      show the lethal effects of AMPH-induced seizures and involvement of multiple and
      complex neurotransmitter systems in this process which requires further
      investigation.

PMID- 14581715
TI  - Synthesis and anticonvulsant activities of 4-N-substituted arylsemicarbazones.
AB  - A series of 4-N-substituted arylsemicarbazones with increased lipophilicity were
      synthesized and evaluated for anticonvulsant activity. The compounds provided
      significant protection against maximal electroshock induced seizures (MES) and
      seizures indicated by sc pentetrazole administration (sc PTZ) at 300 mg/kg after
      0.5 h. The compounds 8 and 4 were active in MES and sc PTZ indicated seizure. The
      study has shown that introduction of alkyl (ethyl) at the terminal amino group
      and alkoxy (methoxy) moiety at the distal aryl ring led to increased activity and
      decreased toxicity.

PMID- 14581716
TI  - Pharmacological evidence that methylene blue inhibits noradrenaline neuronal
      uptake in the rat vas deferens.
AB  - We report that the classical guanylate cyclase inhibitor methylene blue (MB, 1
      microM or 10 microM), but not the selective guanylate cyclase inhibitor 1H
      [1,2,4]oxidazolo[4,3-a]quinoxalin-1-one (1 microM) or nitric oxide synthase
      inhibitor, NG-nitro-L-arginine methyl ester (100 microM), causes a shift to the
      left in the concentration-response curve for noradrenaline in the isolated rat
      vas deferens preparations. The main objective of our study was to investigate the
      pharmacological mechanism by which MB increases the sensitivity of the rat vas
      deferens to noradrenaline. According to the presented results, MB did not change
      rat vas deferens sensitivity to methoxamine or noradrenaline in the presence of
      desipramine (0.1 microM). The pre-contracted rat vas deferens relaxation induced
      by isoproterenol was also not significantly changed by MB (1 microM). Thus, we
      suggest that MB increases rat vas deferens sensitivity through neuronal uptake
      inhibition without interfering in either the nitrergic mechanism or guanylate
      cyclase activity.

PMID- 14581718
TI  - Ethanol induced delayed cellular protection in mouse cardiac myocytes: role of
      inducible nitric oxide synthase.
AB  - This study has examined the hypotheses that, firstly, the ethanol induces delayed
      cellular protection in mouse cardiac myocytes against subsequent sustained
      simulated ischemia (SI). Secondly, the delayed cyto-protective effect induced by
      the ethanol depends more on time than the dose in mouse cardiac myocytes.
      Finally, ethanol-induced delayed cellular protection in mouse cardiac myocytes is
      mediated through inducible nitric oxide synthase (iNOS). Accordingly, we planned
      the following groups of BALB/c mouse cultured cardiac myocytes in our study: (a)
      SI, (b) 5 mM ethanol (ETOH)/15 min + SI, (c) 5 mM ETOH/30 min + SI, (d) 10 mM
      ETOH/15 min + SI, (e) 10 mM ETOH/30 min + SI, (f) 25 mM ETOH/15 min + SI, (g) 25
      mM ETOH/30 min + SI, (h) 25 mM ETOH/60 min + SI, (i) 50 mM ETOH/15 min + SI, (j)
      50 mM ETOH/30 min + SI, (k) 50 mM ETOH/60 min + SI, (l) 250 mM ETOH/15 min + SI
      and (m) 250 mM ETOH/30 min + SI. Another set of experiments we designed with iNOS
      /- and its wild-type (iNOS+/+) mice cardiac myocytes as follows: SI, 5 mM ETOH/30
      min + SI, 10 mM ETOH/30 min + SI, 25 mM ETOH/30 min + SI, 50 mM ETOH/30 min + SI
      and 250 mM ETOH/30 min + SI. Cellular injury was measured by the release of
      creatinine kinase (CK, U/l) into the medium. BALB/c mouse cardiac myocytes
      subjected to SI demonstrated significant increase in CK release as compared to
      the ethanol-treated cells. Ethanol-induced delayed cellular protection resulted
      in a significant (p < 0.001) attenuation in the cellular injury as indicated by
      reduction in the release of CK (U/l) from 9.25 +/- 0.52 to 5.16 +/- 0.44 (5 mM
      ETOH/30 min), from 7.50 +/- 0.43 (10 mM ETOH/15 min) to 4.16 +/- 0.64 (10 mM
      ETOH/30 min), from 5.91 +/- 0.41 (25 mM ETOH/15 min) to 2.50 +/- 0.58 (25 mM
      ETOH/30 min) and to 2.25 +/- 0.37 (25 mM ETOH/60 min), from 5.41 +/- 0.28 (50 mM
      ETOH/15 min) to 1.66 +/- 0.56(50 mM ETOH/30 min) and to 1.25 +/- 0.30 (50 mM
      ETOH/60 min), and from 5.25 +/- 0.21(250 mM ETOH/15 min) to 1.66 +/- 0.51(250 mM
      ETOH/30 min). Reduction in CK release from ethanol-treated iNOS-/-mouse cardiac
      myocytes was insignificant (p > 0.05) compared to non-treated wild-type (iNOS+/+)
      mouse cardiac myocytes subjected to SI alone. Our data suggest that ethanol
      induces delayed cellular protection in mouse cardiac myocytes against sustained
      simulated ischemia. Further, ethanol-induced delayed cellular protection depends
      more on time than the dose. Furthermore, ethanol-induced delayed cellular
      protection is dependent on iNOS.

PMID- 14581717
TI  - Effect of the vascular endothelium on contractions induced by noradrenaline and
      phenylephrine in perforating branch of the human internal mammary artery.
AB  - The effects of noradrenaline (Nor) and phenylephrine (Phe) on the isolated, non
      precontracted perforating branch of the human internal mammary artery (HIMA) were
      investigated. Nor and Phe induced concentration-dependent contractions of intact
      and endothelium-denuded arterial rings with no statistically significant
      differences between the pEC(30) and maximal response values. The pretreatment of
      arterial rings with indomethacin had no effect on Nor- and Phe-induced
      contractions of both, intact and endothelium-denuded preparations. The pre
      addition of L-NMMA did not affect contractions of perforating branch of the HIMA
      evoked by Nor, but provoked significant potentiation of Phe-induced contractions
      of perforating branch of the HIMA both intact and denuded of endothelium only at
      Phe concentration higher than 3 x 10(-6)M. The effects of selective alpha1
      adrenoceptor antagonist, prazosin and selective alpha2-adrenoceptor antagonist,
      rauwolscine were concentration-dependent, and they induced a significant shift to
      the right (for both studied antagonists) of the concentration-response curves for
      Nor in both preparations with or without endothelium. The effects of prazosin and
      rauwolscine on the concentration-response curves for Phe were similar. In
      conclusion, this study has shown that Nor and Phe induce concentration-dependent
      contractions of the perforating branch of the HIMA. Removal of the endothelium
      did not modify this effect. Products of cyclooxygenase pathway had no influence
      on Nor and Phe action. Endothelium derived nitric oxide (NO) had no modulatory
      effect of Nor-induced contractions, but inhibition of NO synthesis provoked
      potentiation of Phe-induced contractions either in intact or endothelium-denuded
      preparations. The mechanism of this effect remains still unclear. On the basis of
      differential affinity of the antagonists and affinities of Nor and Phe
      themselves, we suggest that alpha1-adrenoceptor subtype is probably involved in
      the Nor- and Phe-induced contraction of the perforating branch of the HIMA both
      intact or denuded of endothelium.

PMID- 14581720
TI  - Evaluation of ofloxacin penetration into the skin after a single oral dose
      assessed by cutaneous microdialysis.
AB  - An antibacterial drug can exert its therapeutic action if it is present in target
      tissue at proper concentration. Cutaneous microdialysis is a relatively new
      technique, which allows to determine drug concentration in the skin. The aim of
      the study was to evaluate the ofloxacin concentrations in plasma and skin
      following a single oral dose of 0.4 g. Drug concentration in the skin was
      assessed by applying cutaneous microdialysis. The penetration of the studied
      agent into dermal microdialysate was compared with its penetration into
      theoretical peripheral compartment. Maximum ofloxacin concentration in plasma was
      9.26 micromol/l on average and was achieved after about 1.7 h. Mean peak
      concentrations in cutaneous microdialysate and in theoretical peripheral
      compartment were comparable (4.16 versus 4.50 micromol/l), but time to peak
      concentration in theoretical peripheral compartment was significantly longer than
      in microdialysates (5.8 and 2.0 h, respectively). Degree of penetration into
      cutaneous microdialysate was about 0.54. Cutaneous microdialysis seems to be a
      valuable technique to evaluate drug penetration into the skin.

PMID- 14581719
TI  - Glycine modulates hepatic lipid accumulation in alcohol-induced liver injury.
AB  - We studied the effect of administering glycine, a non-essential amino acid, on
      serum and tissue lipids in experimental hepatotoxic Wistar rats. All the rats
      were fed standard pellet diet. Hepatotoxicity was induced by administering
      ethanol (7.9 g kg(-1)) for 30 days by intragastric intubation. Control rats were
      given isocaloric glucose solution. Glycine was subsequently administered at a
      dose of 0.6 g kg(-1) every day by intragastric intubation for the next 30 days.
      Average body weight gain at the end of the total experimental period of 60 days
      was significantly lower in rats supplemented with alcohol, but improved on
      glycine treatment. Feeding alcohol significantly elevated the levels of
      cholesterol, phospholipids, free fatty acids and triglycerides in the serum,
      liver and brain as compared with those of the control rats. Subsequent glycine
      supplementation to alcohol-fed rats significantly lowered the serum and tissue
      lipid levels to near those of the control rats. Microscopic examination of
      alcohol-treated rat liver showed inflammatory cell infiltrates and fatty changes,
      which were alleviated on treatment with glycine. Alcohol-treated rat brain
      demonstrated edema, which was significantly lowered on treatment with glycine. In
      conclusion, this study shows that oral administration of glycine to alcohol
      supplemented rats markedly reduced the accumulation of cholesterol,
      phospholipids, free fatty acids and triglycerides in the circulation, liver and
      brain, which was associated with a reversal of steatosis in the liver and edema
      in the brain.

PMID- 14581721
TI  - Effect of experimental diabetes on pharmacokinetic parameters of lidocaine and
      MEGX in rats.
AB  - The aim of the study was to evaluate the effect of experimental diabetes on
      pharmacokinetic parameters of lidocaine and its metabolite monoethyl
      glycylxylidide (MEGX) after a single intravenous administration in rats. The
      study was performed on male Wistar rats, randomized into 2 groups: group I-
      control animals and group II--animals with experimental diabetes induced by
      streptozotocin. Evaluation of lidocaine pharmacokinetics was performed 10 days
      after streptozotocin administration. Lidocaine concentrations were lower in rats
      with experimental diabetes compared with the values in the control group. In rats
      with diabetes, the shorter phase of distribution and faster drug elimination has
      been observed. During the pharmacokinetic study, the dynamic reduction of
      lidocaine concentration was accompanied by the increase in MEGX concentration in
      blood. Drug elimination rate constant (gammaz) increased by 68% in rats with
      experimental diabetes which had an effect on the shortening of lidocaine half
      life in those animals (t1/2 by 39%) and on the increase in absolute clearance
      (CL) to 1.46 l/h comparing to control group (0.95 l/h), i.e. by 54%. The
      distribution rate constant of lidocaine (gamma1) was significantly greater in the
      animals with experimental diabetes (by 138%). The volume of distribution (Vd) in
      those animals decreased by 30% in comparison with the control group. The area
      under the plasma concentration-time curve (AUC) decreased by 48% in rats with
      experimental diabetes. The MEGX half-life (t1/2) increased from 0.34 h in the
      control group to 0.89 h in the rats with diabetes, i.e. by 165%. It reflects the
      impaired MEGX elimination in experimental diabetes. The results suggest that
      experimental diabetes can have an effect on lidocaine pharmacokinetics towards
      enhanced lidocaine elimination with accompanied increase in its metabolite (MEGX)
      concentration.

PMID- 14581722
TI  - Influence of tamoxifen on the mandible bone and hard teeth tissues of animals.
AB  - Tamoxifen, protactedly used, can cause disadvantageous changes in the bones and
      in the hard teeth tissues. The aim of this paper was to define to what extent
      tamoxifen given to the animals influences the structure of the mandible bone and
      the hard teeth tissues.

PMID- 14581723
TI  - Proximal tubule damage in patients treated with gentamicin or amikacin.
AB  - The present study aimed to determine the relationships between time of
      administration and dose of aminoglycosides, the extent of proximal tubule damage,
      evaluated by the urine N-acetyl-beta-D-glucosaminidase (NAG) activity, and to
      compare proximal tubule dysfunction in the patients treated with gentamicin and
      those receiving amikacin. The measurement of activity of NAG in urine was chosen
      to monitor of proximal tubule function. The studies were performed in 25
      patients, who had to be administered gentamicin or amikacin by intramuscular
      injections. In both groups, the maximum NAG activities in urine were detected
      most frequently after the 7th day of the therapy. A significant difference in NAG
      activities in urine was noted between the values observed in the course of
      treatment with aminoglycosides and those determined before start of the
      treatment. NAG activity in urine significantly decreased following
      discontinuation of aminoglycoside antibiotic administration. The activities did
      not decrease quite to the pretreatment level but the remaining difference proved
      to be insignificant. In the course of aminoglycoside treatment, 7 patients
      demonstrated an increase in serum creatinine levels exceeding 0.4 mg%. It should
      be stressed that no pronounced differences in nephrotoxicity and, in particular,
      in their potential to induce injury to the proximal tubule have been disclosed
      between gentamicin and amikacin. Their significant, damaging effect on integrity
      of proximal tubule was demonstrated, which was evidenced by the clear increase in
      urinary NAG activity during administration of either drug. Nevertheless, only in
      a small fraction of such cases (12-16%), the increase promoted development of
      renal insufficiency, usually of a transient character. Monitoring of the increase
      in urinary NAG activities in line with observations on creatinine levels permits
      to distinguish a subgroup of patients who may be suspected of development of
      overt nephrotoxicity. In such cases cessation of aminoglycoside administration is
      required.

PMID- 14581724
TI  - Gender differences in the pharmacokinetics of ethanol in saliva and blood after
      oral ingestion.
AB  - The aim of this study was to compare the pharmacokinetics of ethanol in saliva
      and blood according to gender and to evaluate the determination of ethanol in
      saliva for evidential sobriety testing. Twenty-four persons, 12 men and 12 women,
      took part in the experiments. The subjects received ethanol, as neat 40% v/v
      vodka, in the amount which should lead according to Widmark formula to the blood
      alcohol concentration equal to 1.0 g/l. Duplicate samples of an unstimulated
      mixed saliva secretion and venous blood were taken at 15 min intervals timing
      from the end of consumption, and ethanol concentrations in both specimens were
      determined by means of gas chromatography. The pharmacokinetic calculations were
      done using first-order absorption and Michaelis-Menten or zero order elimination
      models. In most cases ethanol reached higher maximal concentration in saliva than
      in venous blood, and was faster eliminated from saliva. The significant gender
      differences in the time-concentration profiles were observed. The maximal ethanol
      concentrations, both in blood and saliva, were lower in women compared to men. In
      females, ethanol was faster excreted from the body. Both experimental (Cmax) and
      extrapolated to zero time (C0) maximum ethanol concentrations were lower in
      females. The apparent volumes of distribution after oral dose for saliva and
      blood were very close and did not differ statistically. The study shows that the
      same factor equivalent to volume of distribution should be used in back
      calculation of alcohol concentration, and saliva alcohol analysis can be treated
      as independent method to test sobriety.

PMID- 14581726
TI  - Influence of some convulsant agents on the protective activity of a novel
      antiepileptic drug, felbamate, against maximal electroshock in mice.
AB  - The aim of this study was to evaluate effects of strychnine, as well as
      bicuculline and picrotoxin on the anticonvulsant action of felbamate against
      maximal electroshock (MES)-induced seizures in mice. Strychnine (up to 0.5
      mg/kg), bicuculline (up to 2 mg/kg) and picrotoxin (3 mg/kg) did not affect the
      seizure threshold. However, strychnine (0.25-0.5 mg/kg) and picrotoxin (3 mg/kg)
      impaired the protective activity of felbamate against MES. It may be concluded
      that GABAergic inhibition and strychnine-insensitive glycine receptor-mediated
      events may contribute to the anticonvulsant activity of felbamate.

PMID- 14581725
TI  - Effect of nimesulide, rofecoxib and celecoxib on gastric tissue glutathione level
      in rats with indomethacin-induced gastric ulcerations.
AB  - Glutathione (GSH) is a tripeptide and a superoxide radical scavenger and it
      protects thiol protein groups required for maintaining the integrity of cell
      against oxidation. GSH is present in the stomach at high concentrations and plays
      an important role in maintaining the integrity of the gastric mucosa. We
      investigated whether oral administration of nimesulide, rofecoxib and celecoxib,
      selective COX-2 inhibitors, changed GSH level in the gastric tissue of
      indomethacin-treated rats. Thirty albino Wistar rats were used in this study.
      Animals were randomly assigned to five groups as follows: control group received
      only distilled water (group I). Nimesulide at a dose of 100 mg/kg (group II),
      rofecoxib at a dose of 25 mg/kg (group III) and celecoxib at a dose of 100 mg/kg
      (group IV) were intragastrically administered 5 min before indomethacin (25
      mg/kg) treatment. Equal volume of distilled water was given to the indomethacin
      administered group (group V). Indomethacin was administered intragastrically.
      Gastric tissue mean GSH level was significantly higher in nimesulide-given rats
      than in rofecoxib- and celecoxib-treated groups, there was not any significant
      difference between the nimesulide and control groups. Our study showed that
      although nimesulide prevented the indomethacin-induced gastric ulcers completely,
      rofecoxib and celecoxib did not prevent the indomethacin-induced ulcer formation.
      In conclusion, we propose that nimesulide exerts a prophylactic effect on the
      indomethacin-induced gastric ulcers by enhancing gastric GSH level.

PMID- 14581727
TI  - Effects of cytochrome P-450 inducers on the perazine metabolism in a primary
      culture of human hepatocytes.
AB  - The metabolism of perazine in a primary culture of human hepatocytes after
      treatment of cells with TCDD (a CYP1A1/2 inducer) or rifampicin (mainly a CYP3A4
      inducer) were studied in vitro. The concentrations of perazine and its main
      metabolites (perazine 5-sulfoxide, N-desmethylperazine) formed in hepatocytes
      were assayed in the extracellular medium using the HPLC method. TCDD and
      rifampicin induced the formation of perazine 5-sulfoxide, however, such an effect
      was not observed in the case of N-desmethylperazine. The accumulation of perazine
      5-sulfoxide in the extracellular medium was enhanced until up to 4 h by
      rifampicin, and until up to 8 h byTCDD. After 24 h, perazine and perazine 5
      sulfoxide were not detected in the extracellular medium of the inducer-treated
      cultures, except for perazine 5-sulfoxide in the TCDD-treated cultures The
      obtained results indicate that CYP1A2 and CYP3A4 are involved in the perazine
      metabolism via 5-sulfoxidation pathway.

PMID- 14581728
TI  - Comparative effect of physiological levels of leptin and insulin on cyclic AMP
      induced stimulation of hepatic glycogen breakdown.
AB  - Physiological level of insulin showed more prominent inhibiting effect on the
      activation of hepatic glucose production and glycogenolysis promoted by cAMP than
      physiological levels of leptin.

PMID- 14581729
TI  - Investigation of outbreaks in India. How good are we at it?

PMID- 14581730
TI  - A comparative clinical trial of artemether and quinine in children with severe
      malaria.
AB  - OBJECTIVE: To compare the efficacy of artemether and quinine in the treatment of
      severe malaria in hospitalized children. STUDY DESIGN: Open randomized trial.
      SETTING: Pediatric ward of a tertiary care center. METHODS: All children admitted
      with clinical manifestations of severe malaria (as per WHO criteria) and asexual
      forms of Plasmodium falciparum demonstrated on peripheral smear were randomized
      to receive either artemether or quinine. Their clinical status and smears for
      parasite count were assessed every 12 hours until two successive blood films were
      negative. The primary end point of the study was death in the hospital and
      residual damage to the organ involved. The secondary end points were clearance of
      parasites and fever, length of time of recovery from coma and normal functions of
      the involved system. RESULTS: Forty-six cases completed the study protocol, 23
      assigned to each drug group. Cerebral malaria was the commonest manifestation
      (76.1%). Mean age in artemether versus quinine group (6.6 +/- 3.5 and 5.8 +/- 2.4
      years) as well as degree of parasitemia at admission (55,800 and 60,300 per
      microlitre) were comparable. The overall mortality rate was 23.9% with no
      significant difference between the two groups. Twenty six cases (56.5%) presented
      with more than one manifestations of severe malaria. The mortality rate was 100%
      with four coexisting manifestations of severe malaria. Fever clearance time in
      artemether and quinine group was 44.5 and 45.9 hours respectively (P >0.05).
      Parasite clearance time was significantly shorter in artemether group (40.9 vs.
      51.9 hours; P<0.001). Recovery from coma was shorter in artemether group (34.8
      vs. 38.1 hours; P<0.05). CONCLUSION: Cerebral malaria is the most common
      manifestation of severe malaria in children. Artemether is a good alternative
      drug to quinine for P. falciparum malaria. Mortality rate is directly
      proportional to the number of coexisting manifestations of severe malaria.

PMID- 14581731
TI  - Insulin resistance and lipid profile in the children of young ischemic parents.
AB  - OBJECTIVE: To determine serum levels of insulin, glucose and lipid profile in
      children of young parents with CAD. DESIGN: Cohort study. SETTING: Tertiary care
      teaching hospital. METHODS: Fifty children in the 5-18 years age group of young
      parents (< 45 years) with CAD, evaluated for fasting blood glucose, insulin and
      lipid profile compared with children of normal parents in the same age group.
      RESULTS: Serum total and LDL-Cholesterol, blood sugar and B.P., both systolic and
      diastolic were significantly higher in test group as compared to controls though
      there was no significant difference observed for weight and body mass index (BMI)
      between the two groups. The insulin levels were also significantly high in the
      test cases.

PMID- 14581732
TI  - Vascular rings: an important cause of persistent respiratory symptoms in infants
      and children.
AB  - OBJECTIVE: To study the pattern of symptomatic vascular rings in infants and
      children with particular reference to clinical features, investigations and
      management. SETTING: Tertiary Care Paediatric Cardiology Division at the Royal
      Hospital, Muscat, Sultanate of Oman. DESIGN: Retrospective study. METHODS: Data
      on all patients aged less than 13 years diagnosed to have symptomatic vascular
      rings at the Royal Hospital, Muscat, Oman from 1992 to 2001 were retrieved from
      hospital records. RESULTS: Sixteen patients, 8 males and 8 females, aged 15 days
      to 36 months were identified, and included 12 with double aortic arch and 4 with
      right aortic arch, aberrant left subclavian artery and ligamentum arteriosum.
      Associated intracardiac defects were not found in any. Noisy breathing (7/16),
      stridor (6/16), respiratory distress (5/16) and recurrent respiratory infections
      (5/16) were the common modes of presentation. The duration from onset of symptoms
      to diagnosis ranged from 3 weeks to 24 months. Besides suggestive clinical
      features, the diagnosis was suspected from the chest radiograph (presence of
      right aortic arch) in 7 patients and from 2-Dimensional echocardiography and
      Doppler studies in 5 patients. Barium swallow studies, however, documented the
      abnormal esophageal indentation in all the 16 patients. Confirmatory imaging
      techniques included digital subtraction angiography in 7/16, cardiac
      catheterization and angiography in 5/16, and CT and MRI of the chest in 2 each.
      All 16 patients underwent successful surgical repair, and 13/16 became
      asymptomatic. 3 patients continued to suffer from occasional respiratory
      infections. CONCLUSIONS: A high index of clinical suspicion coupled with the use
      of barium oesophagraphy enabled early diagnosis in patients with symptomatic
      vascular rings, and surgical repair could be performed successfully in all
      patients.

PMID- 14581733
TI  - Choosing antibiotics for community acquired pneumonia.

PMID- 14581734
TI  - IAP Committee for Protection of Child Consumer: statement on Metoclopramide usage
      in children.

PMID- 14581735
TI  - Persistent pneumonia in children.
AB  - With the aim to study the clinical profile and describe the predisposing causes
      of persistent pneumonia in Indian children, the clinical details and the
      investigations of children presenting with persistent pneumonia to
      Pediatric/Chest Clinic services of a tertiary care center in north India were
      reviewed. Nineteen children (16 boys) were evaluated for persistent pneumonia
      over a period of 5 years. Based on the clinical features and the results of the
      investigations, underlying illness could be identified in 16 (84.2%) children.
      The most frequent underlying causes for persistent pneumonia in children were
      asthma (26.3%) and post-tubercular bronchiectasis (26.3%).

PMID- 14581736
TI  - Anthropometric profile and perinatal outcome of babies born to young women (< 18
      years).
AB  - This study was conducted to ascertain the sociodemographic profile, maternal
      characteristics, neonatal anthropometry and perinatal outcome in adolescent
      pregnancy (18 years or less). 128 consecutive primiparous women more than 18
      years of age served as the control group. There were 4556 deliveries during the
      study period. Young adolescents accounted for 1.25% of total pregnancies. The
      proportion of shorter (<145 cm), lighter (<45 Kg), and anemic (Hb. <9 g/dL) women
      was significantly higher in the study group. Incidence of premature delivery in
      the young adolescents was significantly higher. Mean birth weight, length, head
      circumference and chest circumference of full-term babies of adolescent mothers
      were significantly lower.

PMID- 14581737
TI  - Nutritional parameters in children with malignancy.
AB  - Nutritional status of 44 children with newly diagnosed malignancy was evaluated
      by anthropometric, hematological and biochemical parameters before initiating
      therapy and response to therapy was assessed during follow up. Malnutrition was
      seen in 56.8% children by weight for age criteria (WFA <-2 z). Low hemoglobin was
      found in 82% children, 25% had low total proteins (<5.7 g/dL), 20.5% low serum
      albumin (<3.2 g/dL), 27.3% low serum transferrin (<210 mg/dL) and 16.3% low serum
      iron (<60 ug/dL). Mean anthropometric and biochemical parameters were higher
      among the survivors compared to non-survivors. Significant difference between the
      well nourished and the malnourished group was detected in the achievement of
      remission/response (69.5% vs 38.1%), delays in therapy (8. 7% vs 38.1%) and
      mortality (30.5% vs 61.9%). Complications like febrile neutropenia and bleeding
      were more in the malnourished group. A statistically significant higher incidence
      of infection was seen in children with serum iron<60 ug/dL than those with higher
      values of serum iron (42.8% vs 8%). Malnutrition is a major determining factor in
      treatment planning, complication rates, response to therapy and survival.

PMID- 14581738
TI  - Anemia and undernutrition among preschool children in Uttar Pradesh, India.
AB  - This study was conducted to assess the prevalence of anemia among preschool
      children (3-5 years) and its association with malnutrition in rural Barabanki
      district of Uttar Pradesh, India. Three out of 18 sub-centers in Nindura block,
      Barabanki, each with six villages, were randomly selected for this survey and 654
      boys and 546 girls were included. Mean hemoglobin level in g/dL among boys and
      girls was 10.1 (SD: 1.66) and 9.9 (SD: 1.67) (P <0.06) respectively. The
      proportion of anemic children (Hb <11 g/dL) was 70%. Boys were heavier and taller
      as compared to girls. Among the 67.3% underweight children the mean hemoglobin
      level was 9.85 (SD: 1.67) as compared to 10.39 (SD: 1.62) in those without
      malnutrition (P <0.0001). Likewise, stunted children (87.6%) had statistically
      significantly lower mean hemoglobin levels than those not stunted. The odds ratio
      of an underweight and stunted child having moderate to severe anemia was 1.66.
      While more than half caretakers knew about the term "anemia " and associated
      physical weakness with it, only very few (2.5%) knew that iron intake will
      improve it. They relied on "doctors" (86.7%) for anemia prevention.

PMID- 14581739
TI  - Maternal and neonatal profile and immediate outcome in ELBW babies.
AB  - The present study was designed to ascertain the maternal and neonatal profile and
      immediate outcome of extremely low birth weight (ELBW) babies at a Level III
      neonatal intensive care unit (NICU). Case records of ELBW inborn babies delivered
      between August 2000 and August 2001 were analyzed by using a preset proforma. A
      total of 52 ELBW babies were admitted in NICU in the relevant period, out of
      which 30 (57%) survived. Maternal anemia and previous pre-term (PT) delivery were
      the common predisposing factors for PT delivery. Mean gestational age was 27.8
      weeks and mean birth weight was 831 grams. Mortality was highest in babies less
      than 28 weeks gestation. Neonatal hyper-bilirubinemia (78%) and HMD/RDS (65%)
      were the commonest morbidity. Retinopathy of Prematurity (ROP) screening could be
      done in 35 babies (68%), out of which 22 were found to be normal.

PMID- 14581740
TI  - Portal vein thrombosis complicating neonatal hepatic abscess.
AB  - Hepatic abscess in a neonate is a rare but serious disorder. Diagnosis of hepatic
      abscess requires a high index of suspicion in any septic neonate. CT scan and
      ultrasound of liver are the most sensitive diagnostic tests in detection of
      hepatic abscess. Portal vein thrombosis and portal cavernoma formation is
      hitherto unreported complication of neonatal hepatic abscess in English
      literature. Present case report highlights the difficulty in diagnosis of
      neonatal hepatic abscess and describes the development of portal vein thrombosis
      and cavernoma during its treatment.

PMID- 14581741
TI  - Varicella complicated by scarlet fever.
AB  - We report a 3-year-old boy with varicella complicated by cellulitis and scarlet
      fever. He developed a typical rash of scarlet fever following the onset of
      varicella. Streptococcus pyogenes was isolated from the ulcers due to varicella.
      The present case suggests that scarlet fever may rarely develop following
      varicella and should be considered in children with complicated varicella.

PMID- 14581742
TI  - Partial albinism, immunodeficiency, hypergammaglobulinemia and Dandy-Walker cyst-
      a Griscelli syndrome variant.
AB  - A 6-year-old girl presented with recurrent infections, seizures, regression of
      milestones, silvery hair and organomegaly. A diagnosis of Griscelli syndrome with
      unusual features of a Dandy Walker cyst and hypergammaglobulinemia, not
      previously described in literature, was made. The child was treated with
      supportive measures.

PMID- 14581743
TI  - Cockaney's syndrome.

PMID- 14581744
TI  - Who is at fault?

PMID- 14581746
TI  - Acute superior mesenteric artery syndrome.

PMID- 14581747
TI  - Plea against incidental appendicectomy.

PMID- 14581748
TI  - Uniformity in paracetamol preparations.

PMID- 14581749
TI  - Prevalence of childhood obesity in Chennai.

PMID- 14581751
TI  - Three-periodic nets and tilings: semiregular nets.
AB  - Three-periodic semiregular nets are defined as those with just one kind of vertex
      and one kind of edge, but excluding the five regular and one quasiregular nets
      described earlier. Fourteen of these and their natural tilings are described and
      their importance in crystal chemistry is indicated.

PMID- 14581752
TI  - Three-dimensional reconstruction of the nu-AlCrFe phase by electron
      crystallography.
AB  - The three-dimensional (3D) structure of the huge quasicrystal approximant nu
      AlFeCr (space group P6(3)/m, a = 40.687 and c = 12.546 A) was solved by electron
      crystallography. High-resolution transmission-electron-microscopy (HREM) images
      and selected-area electron diffraction patterns from 13 different zone axes were
      combined to give a 3D potential map. 124 out of 129 unique atoms were found in
      the 3D map. Procedures for ab initio structure determination by 3D reconstruction
      are given. It is demonstrated that 3D reconstruction from HREM images is very
      powerful for solving structures--even very complicated ones. There is no limit in
      terms of the number of unique atoms in a structure that can be solved by 3D
      reconstruction.

PMID- 14581753
TI  - Simultaneous variation of multipole parameters and Gram-Charlier coefficients in
      a charge-density study of tetrafluoroterephthalonitrile based on X-ray and
      neutron data.
AB  - Difficulties encountered in modelling the scattering of fluorine in organic
      compounds have been investigated through refinements of accurate X-ray and
      neutron diffraction data measured on tetrafluoroterephthalonitrile, TFT, at 122.4
      K. Multipole refinements led to a highly contracted octopole on fluorine. The
      subsequent analysis revealed that fluorine does not possess a valence octopole
      but exhibits anharmonic thermal motion that can be modelled by the octopole
      multipole parameters. The scattering contribution from the octopole shows the
      same cubic dependence in the scattering vector as the Gram-Charlier expansion of
      the nuclear displacements to third order. The analysis also showed that
      refinement of third-order Gram-Charlier coefficients on fluorine requires data to
      at least 0.93 A(-1) resolution in sinthetas/lambda. The X-ray data extending to
      1.27 A(-1) were of sufficient resolution to include third-order Gram-Charlier
      coefficients for N, F and the cyano C atoms in the refinement, whereas the
      neutron data only enabled refinement of the third-order Gram-Charlier
      coefficients for nitrogen. The refinements of the neutron and X-ray diffraction
      data yielded identical atomic displacement parameters for all the atoms. Though
      inclusion of anharmonic motion for N and F atoms provides the best model, it does
      not affect the crystal electron density, and all intramolecular bond critical
      points have identical features. Application of the anharmonic model, however,
      leads to small differences in the intermolecular interactions, which is
      illustrated by the electrostatic potential adjacent to the N atom. The
      characteristics of the C-F bond were elucidated by the topological analysis of
      the crystal electron density, which also supported the proposed quinonoid
      structure of the benzene ring.

PMID- 14581754
TI  - The fine structure of X-ray diffuse scattering in the vicinity of high-angle
      superlattice Bragg reflections.
AB  - Triple-axis X-ray diffractometry was used to study diffuse scattering from an
      AlAs/GaAs superlattice grown on an [001]-oriented GaAs substrate by molecular
      beam epitaxy. Reciprocal-space maps were obtained around the 002 reflection from
      the superlattice and its low-angle first-order satellite. The data obtained
      reveal quasi-Bragg diffuse-scattering sheets caused by conformal behavior of
      interfacial roughness as well as amplification of diffuse scattering when the
      incoming or outgoing angle is nearly equal to the Bragg angle of the superlattice
      or substrate. The observed features of diffuse-scattering fine structure are
      explained within the framework of the distorted-wave Born approximation.
      Nevertheless, this approximation is shown to be incorrect for quantitative
      analysis of diffuse scattering. In particular, the observed domination in
      intensity of the incoming Bragg features over the outgoing ones is shown to
      reflect the decay rate of the coherent X-ray field through the diffuse-scattering
      channel, which is not negligible relative to the coherent diffraction.

PMID- 14581755
TI  - Ab initio protein phasing at 1.4 A resolution: the new phasing approach of
      SIR2003-N.
AB  - New algorithms for solving ab initio protein crystal structures have been
      identified and implemented in a modified version of the program SIR2002. They
      succeed in solving numerous protein structures diffracting at atomic resolution;
      the solution was also attained when data were cut at 1.4 A resolution. The direct
      space refinement procedure of SIR2003-N takes advantage of using the envelope of
      the protein, calculated during the phasing process from the current phases. The
      electron-density map is modified by assuming different weights for pixels within
      the envelope or out of it, so tentatively depleting the intensities of the false
      peaks. The map is then inverted and the resulting phase sets may improve their
      values. The new phasing strategy is also based on an optimal use of some figures
      of merit, one of which may be successfully applied in the early stages of the
      phasing process: only the most promising trials are submitted to the complete
      phasing procedure, so saving computing time. SIR2003-N has been successfully
      applied also in solving some protein structures diffracting at 1.4-1.5 A
      resolution.

PMID- 14581756
TI  - The estimation of three-phase invariants when anomalous scatterers are present:
      the limits.
AB  - The probabilistic formula provided by Hauptman and Giacovazzo for estimating
      three-phase invariants when anomalous scatterers are present is revisited. Its
      main defects are: (a) it is absolutely resistant to any attempt at interpreting
      it in terms of parameters accessible via the experiment; (b) its calculation is
      time consuming and requires computing resources. A distribution based on
      interpretable estimates of the parameters is proposed. The role of the old and
      the new expressions in the single-wavelength anomalous diffraction (SAD)
      techniques is discussed, and compared with the role of analogous formulas
      estimating triplet invariants from isomorphous diffraction data.

PMID- 14581757
TI  - Phase extension in crystallography using the iterative Fienup-Gerchberg-Saxton
      algorithm and Hilbert transforms.
AB  - A procedure for phase extension in electron crystallography is proposed based on
      the iterative Fienup-Gerchberg-Saxton algorithm in combination with the use of
      discrete Hilbert transforms. This transform is used to provide oversampling in
      reciprocal space, thus satisfying the Shannon sampling requirement and
      introducing reflections with fractional indices. When the procedure is combined
      with the knowledge of a small set of strong phased Bragg reflections from
      electron-microscope images (or direct methods), the magnitudes of many non-Bragg
      reflections can be calculated with useful accuracy, thus enhancing the
      performance of the iterative algorithm for phase extension. The effects of
      various constraints used in the iterative algorithm are discussed. In this way,
      it is shown that the iterative algorithm conventionally used for phasing diffuse
      scattering from non-periodic objects can also be applied to problems in
      conventional crystallography to find the phases of high-order (resolution) beams
      from a known set of low-order (resolution) phases.

PMID- 14581759
TI  - Report of the Executive Committee for 2002.

PMID- 14581758
TI  - Crystallography of a new metastable phase in Zr-N alloy.
AB  - Selected-area and convergent-beam electron diffraction were used to determine the
      lattice, point and space groups of a new metastable phase (designated the pi
      phase) in the Zr-N system. The pi phase has a body-centered tetragonal lattice
      with a approximately 0.66 nm and a c/a ratio of 0.81. The point-group symmetry of
      the phase is 4/mmm and the space group is I4/mmm.

PMID- 14581761
TI  - Endoscopic, histological and serologic findings of gastric hyperplastic polyps
      after eradication of Helicobacter pylori: comparison between responder and non
      responder cases.
AB  - BACKGROUND: Evidence indicates that eradication of Helicobacter pylori leads to
      the disappearance of hyperplastic polyps in the stomach. However, there are some
      exceptions. We have compared endoscopic and serologic findings of responder and
      non-responder cases with hyperplastic polyps to try to identify the cause(s),
      other than H. pylori infection, of the formation or growth of gastric
      hyperplastic polyps. METHODS: We retrospectively studied 33 patients whose
      hyperplastic polyps disappeared after eradication of H. pylori and 10 patients
      whose hyperplastic polyps did not disappear after eradication. The patients were
      examined both endoscopically and serologically before, 1-3 months after and 12-15
      months after the eradication. RESULTS: The responder and non-responder groups
      were similar with respect to age, sex, coexisting diseases, and histologic
      findings. The number and maximum size of polyps tended to be larger before
      treatment in the non-responder group than in the responder group. The serum
      gastrin level was higher in the non-responder group than in the responder group
      before, 1-3 months after and 12-15 months after the eradication (p=0.0096, p>0.2,
      p=0.0014). On histologic examination, similar reductions in the degree of
      inflammatory cell infiltration in the gastric mucosa of the antrum and body were
      seen in both the responder and non-responder groups. In the non-responders, the
      size and numbers of the polyps regressed in 5 of the 10 patients. The score of
      glandular atrophy in the antrum and the serum gastrin levels in the non-regressed
      cases was higher than those in the regressed cases at 1-3 and 12-15 months after
      eradication. CONCLUSION: Persistent high gastrin levels were found in the non
      responder cases with gastric hyperplastic polyps.

PMID- 14581762
TI  - An open-label pilot study of granulocyte colony-stimulating factor for the
      treatment of severe endoscopic postoperative recurrence in Crohn's disease.
AB  - BACKGROUND/AIM: Recombinant human granulocyte colony-stimulating factor (rhG-CSF)
      promoted healing of Crohn's disease (CD)-like intestinal lesions in chronic
      granulomatous disease and glycogen storage disease Ib, both characterized by
      defective neutrophil functions. We performed a prospective, open-label pilot
      study with rhG-CSF for the treatment of CD. PATIENTS AND METHODS: Five patients
      with clinically inactive CD, but with severe endoscopic ileitis within 1 year
      after intestinal resection and ileocolonic anastomosis, received 300 microg of
      rhG-CSF (Filgrastim; Neupogen) subcutaneously, three times weekly for a total of
      12 weeks. Safety was evaluated by assessment of clinical and laboratory data and
      disease activity. The primary parameter of efficacy was complete mucosal healing,
      as defined by the Rutgeerts score. Anti-inflammatory mediators were repeatedly
      measured during treatment. RESULTS: All patients completed the protocol in
      clinical remission. In 1 subject transient headache resolved after halving the
      rhG-CSF dosage. Complete mucosal healing was observed in 2 patients: in 1 patient
      after 12 weeks of therapy and in 1 patient 9 months after treatment cessation. In
      a single patient, closure of an anovaginal and of a perianal fistula was noted.
      Neutrophil counts and interleukin-1 receptor antagonist and soluble tumor
      necrosis factor receptor p55 and p75 levels were found to be increased during
      drug administration. CONCLUSION: rhG-CSF seems to be safe, well tolerated, and
      might provide efficacy in CD.

PMID- 14581763
TI  - Both selective COX-1 and COX-2 inhibitors aggravate gastric damage induced in
      rats by 2-deoxy-D-glucose. relation to gastric hypermotility and COX-2
      expression.
AB  - BACKGROUND/AIM: 2-deoxy-D-glucose (2DG), despite causing gastric hypermotility
      via vagal stimulation, does not by itself induce damage in the stomach but
      produces gross lesions under prostaglandin (PG) deficiency induced by non
      ulcerogenic dose of indomethacin. In this study, we examined the roles PG and
      cyclo-oxygenase (COX) isozymes play in the gastric ulcerogenic effect of 2DG in
      the rat stomach under PG deficiency caused by indomethacin. METHODS: The animals
      were given 2DG i.v. (200 mg/kg as a bolus injection followed by an infusion at
      100 mg/kg), and the mucosa was examined for lesions 8 h later. SC-560 or/and
      rofecoxib was given p.o. 1 h before 2DG treatment. RESULTS: 2DG alone caused
      slight damage in the stomach despite causing acid hypersecretion and
      hypermotility. Neither SC-560 nor rofecoxib alone caused any damage in the
      stomach, yet these agents significantly aggravated 2DG-induced gastric lesions;
      the severity of damage was much greater when SC-560 was given together with 2DG.
      SC-560, but not rofecoxib, enhanced both acid secretion and gastric motility in
      response to 2DG, with a decrease in mucosal PGE2 content. Expression of COX-2 was
      up-regulated in the stomach as early as 2 h after 2DG treatment, and the PGE2
      content was increased when determined 6 h later, in a COX-2-dependent/rofecoxib
      sensitive manner. Both the expression of COX-2 and gastric hypermotility during
      2DG treatment were inhibited by prior administration of atropine but not
      omeprazole, although 2DG-induced gastric lesions were prevented by both agents.
      CONCLUSION: These results suggest that potentiation by indomethacin of 2DG
      induced gastric lesions is related to inhibition of both COX-1 and COX-2, and
      that 2DG up-regulates COX-2 in the gastric mucosa, the event occurring in
      association with gastric hypermotility and contributing to suppression of later
      extension of the damage.

PMID- 14581764
TI  - Influence of somatostatin receptor scintigraphy and CT/MRI on the clinical
      management of patients with gastrointestinal neuroendocrine tumors: an analysis
      in 188 patients.
AB  - AIM: Many studies describe the sensitivities and specificities of computed
      tomography (CT), magnetic resonance imaging (MRI), and somatostatin receptor
      scintigraphy (SRS) in patients with gastrointestinal neuroendocrine tumors (GNT).
      We performed a study to evaluate the influence of these techniques on the
      therapeutic management of patients with advanced stages of GNT. PATIENTS AND
      METHODS: The results of either CT/MRI scans or SRS were reviewed by two
      independent observers who decided on the therapy of a patient. They then had to
      determine whether the results of the complementary imaging modality would change
      the decision. The study design was a matched cross-over study with two groups
      matching in respect to tumor type, imaging modality known first to the observer,
      and number of patients. For further analysis, patients were divided into three
      subgroups dependent on tumor stage (group 1, without metastases, group 2, liver
      metastases, group 3, recurrent disease/extrahepatic metastases). RESULTS: 188
      patients were included into the study. If SRS was known to the observers first,
      CT/MRI changed the therapeutic management in 16.2, 13.9 and 11.4% of the patients
      (subgroups 1-3). SRS changed the therapeutic management in 13.5, 12.5 and 10.3%.
      Overall, CT/MRI would have changed the management in 13.3% and SRS in 11.7% of
      the patients. CONCLUSION: Though the patients studied mainly suffered from
      already advanced stages of the disease, all imaging techniques change the
      therapeutic management to a comparable extent. Our results support the importance
      of combined imaging in the management of patients with GNT.

PMID- 14581765
TI  - Adult autoimmune enteropathy treated successfully with tacrolimus.
AB  - BACKGROUND: Autoimmune enteropathy is a life-threatening, chronic disease of the
      small bowel mucosa, which generally responds well to steroids. Treatment requires
      long-term immunosuppression, and steroid-sparing treatment strategies are
      desirable. Azathioprine and cyclosporine A have limitations, however alternatives
      have not been described in adults. CASE REPORT: We present the case of a 54-year
      old male patient with autoimmune enteropathy who responded initially to a
      standard treatment with steroids, but was dependent on 30 mg prednisolone.
      Medical treatment was changed to tacrolimus after renal function deteriorated
      under treatment with cyclosporine A. Under this regimen, small bowel histology
      normalized and the clinical condition is stable after 2 years of introduction of
      tacrolimus. CONCLUSION: This constitutes the first report of effective treatment
      of adult autoimmune enteropathy with tacrolimus, a substance with a similar mode
      of action to cyclosporine, but with fewer side effects and improved
      bioavailability.

PMID- 14581766
TI  - Spontaneous bacterial peritonitis in a patient with myxedema ascites.
AB  - Ascites is uncommon in patients with hypothyroidism. Herein we describe an 84
      year-old female patient with myxedema ascites that resolved completely with
      thyroid replacement medication. Bacteriological studies of the ascitic fluid
      revealed gram-negative rods which eventually proved to be Klebsiella pneumoniae
      treated successfully with antibiotics. Our review of the literature failed to
      reveal a previous case of myxedema ascites with concomitant subclinical
      spontaneous bacterial peritonitis.

PMID- 14581767
TI  - Twenty years of hip ultrasonography: are we doing better today?

PMID- 14581768
TI  - Six years of experience with a new surgical algorithm in developmental dysplasia
      of the hip in children under 18 months of age.
AB  - One hundred thirty-seven developmentally dysplastic hips of 107 children with a
      mean age of 11 months were treated by the same surgical algorithm. Following
      iliopsoas and adductor longus tenotomies by the Ferguson posteromedial approach,
      the operation was ended in case of arthrographically documented concentric
      reduction (Tonnis grade 1 reduction) and an open reduction was performed in case
      of nonanatomic arthrographic reduction (Tonnis grade 2 or 3 reduction). Mean
      follow-up was 4.2 years. The need for open reduction increased in preoperatively
      dislocated hips that were proximally displaced according to the Tonnis
      classification. Somewhat better latest acetabular index values were seen in hips
      having lower preoperative dislocation grades that were surgically treated before
      the age of 12 months. Rates of avascular necrosis of the femoral head,
      redislocation, and secondary operation were 13%, 1%, and 2%, respectively. The
      authors concluded that although mid-term results of this new surgical algorithm
      in developmental dysplasia of the hip was satisfactory in infants younger than 18
      months of age, long-term follow-up is needed for better understanding of its use.

PMID- 14581769
TI  - Acetabular depth and race in young adults: a potential explanation of the
      differences in the prevalence of slipped capital femoral epiphysis between
      different racial groups?
AB  - Slipped capital femoral epiphysis (SCFE) is known to have a higher prevalence in
      blacks and Polynesians. It has been postulated that a deeper acetabulum increases
      the shearing forces on the proximal femoral physis, resulting in a higher
      incidence of SCFE. It was the purpose of this study to investigate acetabular
      depth in the normal adult population as a function of race. Anteroposterior
      pelvis radiographs from young polytrauma adults (<35 years) were identified. Race
      was classified according as white, black, Amerindian (Hispanic and Native
      American), and Asian. Acetabular depth was measured by Visser's modification of
      the center-edge (CE) angle and Sharp's angle. All measurements were made by one
      observer with the same goniometer and Mose circle. There were 167 patients with
      an average age of 24 +/- 4 years; there were 65 female (39%) and 102 male (61%)
      patients. There were 57 (34%) Amerindian, 50 (30%) white, 47 (28%) black, and 13
      (8%) Asian people. The CE angle was 30.6 +/- 4.8 degrees for the Asian, 28.7 +/-
      5.7 degrees for the black, 30.3 +/- 5.1 degrees for the Amerindian, and 28.0 +/-
      4.3 degrees for the white racial groups. Sharp's angle was 39.8 +/- 3.0 degrees
      for the Asian, 39.9 +/- 3.6 degrees for the black, 37.4 +/- 3.4 degrees for the
      Amerindian, and 39.2 +/- 3.2 degrees for the white racial groups. These
      differences by race were statistically significant for both Sharp's and Visser's
      angles. If racial variation in acetabular depth is an explanation for the racial
      variability of SCFE, then the CE and Sharp's angle should vary by race. In this
      study of healthy adults without any underlying hip pathology, racial variability
      in the CE or Sharp's angle did not follow the racial prevalence of SCFE.

PMID- 14581770
TI  - Center of the femoral head in children: anatomic-radiologic correlation.
AB  - Thirty-six proximal femoral heads of cadaveric specimens between 0 and 33 months
      old were the object of a study for the anatomic and radiologic location of the
      center of the femoral head. The authors verified the sphericity and determined
      their geometric center. The center is found on the physis of the longitudinal
      growth of the neck. X-rays show a correlation with the anatomic dissection of the
      location of the center of the femoral head on the physis at a distance from the
      metaphysis of 3.7 mm in children under 3 months old, 2.3 mm in 3- to 6-month-old
      children, 1.4 mm in children 7 to 18 months old, and 0.2 mm in children 19 to 33
      months old. The way in which the center must be located on a pelvis x-ray is
      described. This center is useful in the measurement of Wiberg's angle in small
      children.

PMID- 14581771
TI  - Posterior acetabular wall deficiency in Down syndrome.
AB  - Trisomy 21 or Down syndrome is the most common chromosomal anomaly and is
      associated with musculoskeletal abnormalities related to a generalized
      ligamentous laxity. Approximately 1% to 7% of Down syndrome patients have hip
      instability. Prior studies on the topic recommend Salter innominate osteotomy,
      capsular plication, and a varus derotational osteotomy of the proximal femur,
      which typically is in an anteverted and valgus position. The authors present a
      previously unreported bilateral finding in two patients noted on three
      dimensional reconstruction computed tomography: deficiency of the posterior
      acetabular wall. Each was treated using a modification of the Pemberton osteotomy
      in which a wedge of iliac crest graft is placed posteriorly to hinge the
      posterior wall into a position of better posterior coverage of the femoral head.
      Both patients' hips have remained stable more than 10 years postoperatively.
      Follow-up imaging demonstrates well-remodeled osteotomy sites and excellent
      posterior coverage of the femoral heads.

PMID- 14581772
TI  - Peripheral circulation in patients with myelodysplasia.
AB  - Patients with myelodysplasia have increased wound dehiscence and ulcer formation
      compared with the normal population. While neurologic deficits and resultant
      muscle imbalance are the presumed etiologies for these complications, no study
      has investigated the role of peripheral circulation in myelodysplasia. Eighty-two
      patients (ages 2-20) were prospectively recruited for this study, consisting of
      41 patients with myelodysplasia and 41 age-matched controls. Peripheral
      circulation was quantified using systolic blood pressures in arms and legs (ankle
      brachial index [ABI]) and transcutaneous pO2 measurements (TcO2) in a
      standardized location in the forefoot. Both groups had similar mean age. Patients
      with myelodysplasia had a lower ABI but similar TcO2 compared with the control
      group. Among the patients with myelodysplasia, the ABI and TcO2 did not vary
      according to the level of neurologic deficit or the patient's age. However, those
      with prior surgical procedures had significantly higher ABI and TcO2 compared
      with those without prior surgery (P < 0.05). This study suggests that patients
      with myelodysplasia may have decreased peripheral circulation compared with
      normal controls. Vascular insufficiency may therefore contribute to increased
      wound healing complications and ulcer formation in these patients.

PMID- 14581773
TI  - Skeletal maturity in myelomeningocele.
AB  - A retrospective analysis of 90 patients (37 boys, 53 girls) with myelomeningocele
      was performed to determine the relationship between gender, presence of
      hydrocephalus, and level of myelomeningocele with skeletal maturity, as measured
      by bone age. Bone age was assessed using the Oxford method of skeletal maturity.
      A ventriculoperitoneal shunt was present in 56 of the 90 patients. The mean bone
      age was found to be significantly less in patients with a ventriculoperitoneal
      shunt. There was no difference in bone age when comparing gender or level of
      myelomeningocele. Identification of factors affecting skeletal maturity in
      patients with myelomeningocele is important in surgical planning for therapeutic
      operations such as osteotomies, timing of epiphysiodesis, and spinal fusion for
      scoliosis.

PMID- 14581774
TI  - Early degeneration of the knee in diastrophic dysplasia: an MRI study.
AB  - Magnetic resonance imaging (MRI) findings of 23 patients (13 females, 10 males;
      45 knees) with diastrophic dysplasia were examined. The age of the patients
      ranged from 5 to 40 years (mean 20.5 years). T1- and T2-weighted MR images were
      obtained. MRI revealed degenerative changes in the articular cartilage of the
      knees from age 6 years. The subchondral bone of the distal femur was often
      fragmented, and cartilaginous intrusions from the growth plate into the
      metaphysis were noted. Menisci developed abnormally. In 43 (96%) of the knees
      studied, the anterior cruciate ligament was either thinned or rudimentary, or
      could not be detected. The posterior cruciate ligament was affected in 40 (89%)
      knees but was at least rudimentary in all patients. In contrast, the patellar
      tendon was thick and short and the patella was in an inferior position The
      patella showed bony fragmentation in 32 (71%) knees. The pathologic changes in
      all joint compartments increased with age, reflecting early degeneration of the
      knee in this disease.

PMID- 14581775
TI  - Role of magnetic resonance imaging in the diagnosis of distal tibia fractures in
      adolescents.
AB  - This prospective study was performed to assess the benefits of magnetic resonance
      imaging (MRI) compared with plain radiographs in the diagnosis and analysis of
      transitional fractures in terms of fracture type, anatomy, and dislocation.
      During a 24-month period, 22 adolescents with a fracture of the distal tibial
      epiphysis were treated. In addition to plain film radiographs, MR images of the
      distal tibia were also obtained. Plain film radiographs and MR images were
      randomized and diagnosed by two surgeons and two radiologists. Fifteen
      transitional fractures were diagnosed using plain radiographs, while 17
      transitional fractures could be found with MRI. Fracture type was misclassified,
      fracture displacement was underestimated in general, and rotational displacements
      were not visualized on plain film radiographs. MRI was found to provide anatomic
      detail and information superior to plain film radiographs.

PMID- 14581777
TI  - Management of congenital pseudarthrosis of the tibia in children under 3 years of
      age: effect of early surgery on union of the pseudarthrosis and growth of the
      limb.
AB  - The study was undertaken to determine whether the results of treatment of
      pseudarthrosis of the tibia in children under age 3 are so poor as to recommend
      that surgery be deferred until after 3 years of age. Radiographs and case records
      of 26 consecutive patients with Crawford type IV congenital pseudarthrosis of the
      tibia who were treated operatively were reviewed. Growth abnormalities of the
      tibia, fibula, and femur of the affected limb at presentation were identified.
      The outcome of treatment, in terms of union of the pseudarthrosis, refracture
      rate, and limb length, in 13 children treated operatively before age 3 years was
      compared with those operated on later. Union of the pseudarthrosis occurred in 12
      of 13 children (92%) who were treated before 3 years of age by excision of the
      pseudarthrosis, intramedullary rodding, and dual-onlay cortical bone grafting.
      Union occurred in only five of seven children who underwent the same procedure
      between the ages of 3 and 12 years. The extent of shortening of the limb at the
      time of surgery was least in children younger than 3 years. The limb length
      discrepancy remained virtually static in 11 children who had transarticular Rush
      rodding before age 3. Growth abnormalities of the fibula, tibia, and femur were
      less pronounced in children operated on early. The study suggests that there is
      no need to defer surgery for pseudarthrosis of the tibia until the child is older
      than 3 years.

PMID- 14581776
TI  - Premature physeal closure following distal tibia physeal fractures: a new
      radiographic predictor.
AB  - The incidence and predictors of premature physeal closure (PPC) after pediatric
      distal tibial fractures were investigated. PPC was defined as evidence of growth
      plate disturbance on the injured side compared with the uninjured side. Ninety
      two fractures were reviewed with at least 1 year of follow-up, or until
      physiologic closure of the growth plates. Twenty-five fractures (27.2%) were
      complicated by PPC, as confirmed by CT scan in most cases. Salter-Harris III and
      IV (medial malleolar type) fractures resulted in the highest percentage of PPC by
      fracture type (38%). Salter-Harris I and II fractures resulted in PPC in 36% of
      cases, followed by triplane fractures (21%) and Tillaux fractures (0%). Initial
      displacement, number of reduction attempts, or treatment method did not
      significantly affect the incidence of PPC. More anatomic reductions resulted in a
      statistically significant decrease in PPC rates. Residual physeal gap (>3 mm)
      following reduction was determined from radiographs in Salter-Harris I and II
      fractures. If a residual gap was seen on the radiograph, the incidence of PPC
      increased to 60%; if no gap was present, the incidence decreased to 17%. Open
      reduction was performed in five Salter-Harris II fractures that had a residual
      gap. Periosteum was entrapped in the physis in all of these cases. Residual gaps
      in the physis following closed reduction may represent entrapped periosteum in
      Salter-Harris I and II fractures. This can lead to a higher incidence of PPC,
      suggesting that open reduction and removal of the entrapped periosteum may be
      beneficial.

PMID- 14581778
TI  - One-step treatment for evolved Blount's disease: four cases and review of the
      literature.
AB  - In infantile tibia vara, the presence of superomedial bridge and sloped plateau
      requires several problems to be addressed: correction of varus deformity and
      internal tibial torsion, prevention of recurrences, restoration of normal joint
      congruity, and prevention and correction of limb length discrepancy. Four
      patients were treated as follows: percutaneous epiphysiodesis of the
      superolateral tibia and proximal fibula, elevation osteotomy of the medial tibial
      plateau, osteotomy of the fibula, and dome-shaped metaphyseal osteotomy of the
      tibia, followed by progressive lengthening. Osteosynthesis was achieved by an
      Ilizarov frame (average 6 months). Latest follow-up (average 6 years 10 months)
      showed that all patients were satisfied, with normal limb length and alignment
      and correct articular surface congruence. Correction of limb alignment,
      restoration of joint surface congruity, prevention of recurrence, and treatment
      of limb length discrepancy are all dealt with in the same procedure.

PMID- 14581779
TI  - Limb salvage in bone sarcomas in patients younger than age 10: a 20-year
      experience.
AB  - The authors present their experience over the last 20 years in limb salvage
      procedures of a consecutive series of 40 children under 10 years of age (range 2
      10 years) with bone sarcomas. Nineteen were osteogenic sarcomas and 21 were Ewing
      sarcomas. Only one case, located in the distal phalanx of the toe, was treated by
      straightforward amputation. Intercalary allografts and Canadell's technique were
      used to preserve joints whenever possible, and prosthesis or osteoarticular
      allografts were used when the joint surface was involved. Survival rate in this
      series was 75%. There were four local recurrences. At the last follow-up (mean
      11.2 years, range 5-19 years postop), 90% of the patients preserved their limbs.
      Eighty percent of the authors' results were excellent or good according to the
      Musculoskeletal Tumor Society Scale. Limb salvage is a real possibility even in
      young children with bone sarcomas. The age of the patient itself is not a
      contraindication for limb salvage.

PMID- 14581780
TI  - Spontaneous remission of massive solitary eosinophilic granuloma of the femur.
AB  - The authors describe two children with a history of pain and limping who showed a
      solitary extensive diaphyseal lesion of the femur. A needle biopsy confirmed the
      diagnosis of eosinophilic granuloma. Without any treatment, both patients went
      into spontaneous total remission after the percutaneous biopsy. At last follow-up
      (after 4 years), there was no clinical evidence of disease, and a femur x-ray
      appeared normal. These two cases suggest that until additional biologic
      parameters of disease behavior are clarified, some patients with eosinophilic
      granuloma might be grossly overtreated due to misinterpretation of radiographic
      images.

PMID- 14581781
TI  - Treatment of simple bone cysts with aspiration and a single bone marrow
      injection.
AB  - The authors report the results of percutaneous aspiration and injection of marrow
      into active, simple bone cyst in 17 cases. Slow regression of the cyst and
      progressive healing were obtained in 13 cases (76%), no response was observed in
      2 cases (12%), and recurrence was observed in 2 others (12%) after a follow-up of
      33.9 months. Cyst evolution was monitored by a cyst index, cyst diameter, and
      computer-assisted densitometric image analysis of serial radiographs.

PMID- 14581782
TI  - Growth plate behavior after desepiphysiodesis: experimental study in rabbits.
AB  - The aim of this work was to study the potential healing of the growth plate in
      the case of a central desepiphysiodesis. A central defect was made in the distal
      femoral growth plate of thirty 3-week-old rabbits. In group A the growth plate
      defect was left empty as control. The defects of group B were implanted with a
      polymeric cylinder fixed in the metaphysis with a pin. In group C the cylinder
      was fixed in the epiphysis. Two months after implantation, clinical, radiologic,
      and histologic analyses were carried out. In group A, the mean shortening was
      12.63%; it was 4.9% in group B and 1.54% in group C. Histologic analysis showed
      constant appearance of an epiphysiodesis after migration of the implant in the
      metaphysis. No regeneration of the growth plate was observed. Prevention of
      migration of the interpositional material is recommended to avoid recurrence of
      an epiphysiodesis.

PMID- 14581783
TI  - Current management of idiopathic clubfoot questionnaire: a multicentric study.
AB  - A survey was mailed to 541 members of the Pediatric Society of North America to
      define currently accepted treatment options in the management of talipes
      equinovarus. Four hundred sixteen (77%) responses were received, representing a
      total of 6125 years in practice (average of 17.4 years per physician) and 8595
      clubfeet treated in the past year (average of 26 feet treated per physician).
      While specific trends were reported and great variability exists, certain
      principles are universal: initial nonoperative management followed by surgery for
      persisting deformities. A renewed interest in Ponseti's techniques of casting and
      surgery to address specific persisting deformities was reflected in this survey.

PMID- 14581784
TI  - Activities scale for kids: an analysis of normals.
AB  - Several outcome tools have been developed to measure physical functioning in
      pediatric orthopedic patients. One such tool, the Activities Scale for Kids
      (ASK), allows assessment of physical functioning in the community in 5- to 15
      year-olds. Previous validation of the ASK showed a significant difference in
      scores according to global ratings of disability. In this study, the ASK was
      administered to children without musculoskeletal disability to determine how
      normal respondents scored. ASK questionnaires were distributed to 137 children
      and 122 (89%) were returned. Normal children scored quite high, with a mean
      summary score of 93.12 (SD 6.45). This score differs significantly from the mean
      summary score for children with mild disabilities as determined in previous
      studies of disability (P = 0.005).

PMID- 14581785
TI  - Glove perforation in pediatric orthopedic practice.
AB  - A prospective study was conducted to assess the glove perforation rate during 100
      consecutive pediatric orthopedic operations. Eight hundred fifty-four gloves were
      tested for perforations. The overall glove perforation rate was 8.43%. Assistant
      surgeons had a rate of 45.8%, surgeons 33.4%, and scrub nurses 20.8%. More
      perforations were noticed on the left glove; the thumb and index finger were the
      most common sites of perforation. The duration of surgery was significantly
      related to the perforation rate. Two patients had postoperative wound infections
      and the gloves of surgeons and assistant surgeons were found to be perforated.
      Every attempt needs to be made to reduce the risk of glove perforation.

PMID- 14581786
TI  - Use of NSAIDs and COX-2 inhibitors in children with musculoskeletal disorders.

PMID- 14581787
TI  - Thoughts on "Langerhans cell histiocytosis of bone in children and adolescents".

PMID- 14581788
TI  - The HIPAA Privacy Rule and its impact on pediatric research.

PMID- 14581789
TI  - Protein-losing enteropathy in patients with fontan operations.

PMID- 14581790
TI  - Feeble cholangiocytes, toxic bile, and nonsyndromic paucity of interlobular bile
      ducts.

PMID- 14581791
TI  - Glutamine supplements in premature infants: why and how.

PMID- 14581792
TI  - Is eicosapentaenoic acid useful in the treatment of ulcerative colitis in
      children?

PMID- 14581793
TI  - Variceal bleeding in children.

PMID- 14581794
TI  - Nonsyndromic paucity of interlobular bile ducts: report of 10 patients.
AB  - OBJECTIVES: Only a few reports of nonsyndromic paucity of interlobular bile ducts
      (NS-PILBD) have been published. The authors' aim was to outline the clinical and
      laboratory profile of patients with NS-PILBD diagnosed at a tertiary referral
      center. METHODS: The authors reviewed all the reports of pediatric liver biopsies
      performed between 1991 and 2000 at their institution. Upon diagnosis of NS-PILBD,
      patients' records were examined for clinical, laboratory, and histologic data,
      and liver biopsy specimens were re-evaluated. RESULTS: Three hundred biopsies
      were performed in children during the study period, of which 64 were in infants
      younger than 1 year. NS-PILBD was diagnosed in 10 of 64 (16%) biopsy specimens.
      Mean age at presentation was 10 days (range, 1 day-6 weeks), and mean follow-up
      was 4.5 years (range, 1-9 years). An underlying condition was identified in 70%
      of children with NS-PILBD: namely congenital cytomegalovirus (n = 2), progressive
      familial intrahepatic cholestasis (PFIC, n = 2), mitochondrial DNA depletion (n =
      1), Niemann-Pick type C (n = 1), and arthrogryposis multiplex congenita, renal
      dysfunction, and cholestasis (ARC syndrome; n = 1). All children presented with
      jaundice. Four children had initially acholic stools. At their last follow-up
      visit, failure to thrive was present in five children, and cholestasis in six
      children. Mortality was noted only in children with metabolic diseases (n = 2).
      CONCLUSIONS: In the study, NS-PILBD was common in young children undergoing liver
      biopsy. Although NS-PILBD is nonspecific, a wide survey for inborn errors of
      metabolism should be included in the diagnostic work-up of NS-PILBD. In the
      authors' center, the association of certain metabolic diseases with NS-PILBD
      carries a grave prognosis.

PMID- 14581795
TI  - A randomized, controlled trial of parenteral glutamine in ill, very low birth
      weight neonates.
AB  - OBJECTIVE: The role of "novel substrates" in neonatal nutrition has generated
      much interest in recent years. Glutamine has been recognized as a "conditionally
      essential" amino acid in critically ill adults, particularly for gut and immune
      function; however, its potential role in the neonate remains unclear. The authors
      examined the safety and benefits of parenteral glutamine in ill, preterm
      neonates. DESIGN: Randomized controlled trial. METHODS: Thirty-five ill preterm
      neonates of <1000 g birth-weight were randomized to receive either glutamine
      supplemented parenteral nutrition (PN) (n = 17) or standard PN (n = 18). RESULTS:
      There were no significant differences in birth-weight, gestational age, male-to
      female ratio, or Clinical Risk Index for Babies (CRIB) score between the two
      groups. During PN there were no significant differences between the groups in
      white cell count, differential white cell count, blood urea nitrogen, plasma
      ammonia, lactate, pyruvate, plasma glutamine, or glutamate. The median time to
      achieving full enteral nutrition (FEN) was shorter in the study group (13 days
      vs. 21 days, P < 0.05). The number of episodes of culture-positive sepsis or age
      at discharge did not differ between groups. CONCLUSIONS: Parenteral glutamine
      appears to be well tolerated and safe in the ill, preterm neonate. It may reduce
      the time to achieving FEN.

PMID- 14581796
TI  - Establishing enteral feeding in preterm infants with feeding intolerance: a
      randomized controlled study of low-dose erythromycin.
AB  - OBJECTIVE: A prospective, double-blind, randomized, controlled trial was
      conducted to evaluate the effect of low-dose erythromycin on the time taken to
      attain full enteral feedings in preterm infants with very low birth weight and
      feeding intolerance. METHODS: Two groups of preterm infants (birth weight </=
      1500 g) with feeding intolerance were randomized to either low-dose erythromycin
      (5 mg/kg every 8 hours) or 5% dextrose placebo, both of which were discontinued 1
      week after full enteral feedings were tolerated. The primary outcome variable was
      the time taken to attain full enteral feedings of at least 130 mL/kg/d. RESULTS:
      The gestational age at birth was similar in the two groups (erythromycin, 27.1 +/
      1.9 weeks; placebo, 27.5 +/- 2.9 weeks). The mean birth weight of the
      erythromycin group was lower (806.3 +/- 215.6 g) than the placebo group (981.4 +/
      285.4 g; P = 0.18), and included more infants who were small for gestational age
      (4/13 = 31% versus 1/11 = 9%; P = 0.224). There was no difference between the two
      groups with regard to the volume of feedings they were receiving at the time of
      enrollment. Reduction in symptoms of gastroesophageal reflux was similar in the
      two groups. 3 of 13 in the erythromycin group and 4 of 11 in the placebo group
      improved during the study (P = 0.565). The mean time to attain full enteral
      feedings after enrollment was 24.9 + 2.9 days in the erythromycin group and 30.8
      +/- 4.1 days in the placebo group, a difference that did not reach statistical
      significance (P = 0.17). CONCLUSIONS: Low-dose erythromycin did not reduce the
      time taken to attain full enteral feedings in preterm infants with very low birth
      weight and feeding intolerance. Gastroesophageal reflux decreased as a
      consequence of maturation of the gastrointestinal tract and not because of
      erythromycin. These preliminary results justify verification in larger
      multicenter trials.

PMID- 14581797
TI  - Does breast feeding influence liver biochemistry?
AB  - OBJECTIVE: It is assumed that early feeding can affect liver biochemistry because
      breast-fed infants have a higher risk of hyperbilirubinemia than formula-fed
      infants. The authors sought to determine how feeding mode affected liver
      biochemistry in healthy term infants. METHODS: Healthy term infants were followed
      up during infancy with a monthly questionnaire about feeding mode. Blood samples
      were obtained at 2, 6, and 9 months. Liver biochemistry (serum albumin, alkaline
      phosphatase, lactic dehydrogenase, aspartate aminotransferase [AST], and
      bilirubin), total insulin-like growth factor 1 (IGF-I), and insulin growth factor
      binding protein 3 (IGFBP-3) were determined at all ages. RESULTS: Mean AST and
      bilirubin were significantly higher in breast-fed infants at 2 and 6 months. In
      addition, mean albumin levels were higher in breast-fed infants at 2 months.
      Alkaline phosphatase, IGF-I, IGFBP-3, and lactic dehydrogenase levels did not
      differ between the feeding groups. AST levels did not correlate significantly
      with bilirubin, albumin, alkaline phosphatase, or lactic dehydrogenase values.
      There was a strong positive association between AST and IGF-I at 2 months (r =
      0.47, P = 0.004). CONCLUSION: Cytomegalovirus infection, vitamin K deficiency,
      and macromolecular forms of AST could be an explanation for a higher AST level
      among breast-fed infants. However, no other clinical or paraclinical sign of
      liver disease was seen, all infants were given oral vitamin K, and the AST did
      not rise to levels comparable to those seen in individuals with macromolecular
      AST. The authors speculate the most likely explanation of the elevated AST is
      induction of hepatocytes by factors in human milk. This is supported by the
      higher albumin levels in breast-fed infants and the positive association between
      AST and IGF-I.

PMID- 14581798
TI  - Increased levels of hemostatic proteins are independent of inflammation in
      glycogen storage disease type Ia.
AB  - OBJECTIVES: Glycogen storage disease type Ia (GSD-Ia), a congenital deficiency of
      hepatic glucose-6-phosphatase activity, is often associated with
      hyperproteinemia. To document the mechanism of hyperproteinemia, the proteins of
      the hemostatic system were analyzed according to their site of synthesis:
      hepatocyte, endothelial cell, or both. The role of inflammation was investigated
      by the measurement of tumor necrosis factor alpha (TNF-alpha) and interleukin-6
      (IL-6) levels in plasma. METHODS: Twenty-seven patients with GSD-Ia were
      evaluated, as were 14 patients with other types of GSD and 30 healthy control
      subjects. Of the 41 patients with GSD, 15 also had hepatic adenoma (14 patients
      with GSD-Ia and 1 with GSD type III). RESULTS: In patients with GSD-Ia, there was
      a two-fold increase in all hepatocyte-synthesized proteins (i.e., factor VII,
      protein C, C4b binding protein) compared with control subjects and patients with
      other types of GSD. The proteins with mixed endothelial and hepatocyte origin
      (i.e., antithrombin and protein S) also were significantly increased but to a
      lesser extent. In contrast, the mean concentration of von Willebrand factor,
      which is exclusively synthesized in endothelial cells, was normal, as was the
      concentration of TNF-alpha and IL-6. CONCLUSIONS: These results suggest that the
      hyperproteinemia of GSD-Ia (including hemostatic proteins) is attributable to
      hepatocyte dysfunction and not related to an inflammatory process.

PMID- 14581799
TI  - Bone mineral density of the lumbar spine in children and adolescents with celiac
      disease on a gluten-free diet in Sao Paulo, Brazil.
AB  - BACKGROUND: To compare bone mineral density (BMD) in children and adolescents
      with celiac disease (CD) and control subjects and to evaluate diet adequacy and
      calcium metabolism in patients with CD. METHODS: Thirty patients with
      asymptomatic CD (17 children, 13 adolescents), on a gluten-free diet, and 23
      healthy subjects were studied. BMD of the lumbar spine (dual energy x-ray
      absorptiometry) was performed on all patients and control subjects. In patients,
      food diaries for nine nonconsecutive days were obtained and analyzed. In
      patients, laboratory tests pertaining to calcium balance were obtained. RESULTS:
      The mean weight and height of the adolescents with CD were lower than those of
      control subjects (weight: 45.8 +/- 10.5 kg v 55.3 +/- 10.5 kg, P = 0.037; height:
      153.0 +/- 11.0 cm v 167 +/- 12.0 cm, P = 0.007). The mean BMD in adolescents with
      CD was significantly lower than that of the control subjects (0.917 +/- 0.116
      g/cm2 v 1.060 +/- 0.158 g/cm2, P = 0.015), whereas no significant difference was
      found between children with CD and control subjects (P = 0.595). A multiple
      regression model shows that increases in BMD relative to height were lower in
      adolescents with CD than in control subjects. The proportion of adolescents who
      had started a gluten-free diet after 2 years of age was higher than that of
      children with CD (P < 0.001). High percentages of magnesium, calcium, and
      phosphorous deficiencies were present in CD patients' diets. The serum levels of
      ionized and total calcium and parathormone were normal. CONCLUSIONS: The BMD of
      adolescents with CD was lower than that of the control subjects, whereas no
      difference was found between the BMD of children with CD and that of control
      subjects.

PMID- 14581800
TI  - Fecal alpha1-antitrypsin concentrations as a measure of enteric protein loss
      after modified fontan operations.
AB  - BACKGROUND: Little is known about the enteric protein loss in patients after a
      modified Fontan operation before the appearance of overt symptoms or signs of
      protein-losing enteropathy (PLE). The authors examined the possibility of using
      fecal alpha1-antitrypsin concentration measurements for the early detection of
      postoperative PLE and in longer term postoperative monitoring of these patients.
      METHODS: The authors compared fecal alpha1-antitrypsin concentrations in stool
      samples from 12 children 12.0 to 43.7 months after modified Fontan operations
      with those of 12 age-matched control subjects and examined the relationship
      between the alpha1-antitrypsin levels and time since operation. The authors also
      compared fecal alpha1-antitrypsin concentrations of stools from the same patients
      obtained at two different time points after surgery with intervals between
      samples ranging from 14.7 to 19.8 months. RESULTS: No significant differences in
      serum total protein and albumin levels were observed between patients after the
      modified Fontan operation and control subjects. The fecal concentrations of
      alpha1-antitrypsin in patients after the Fontan operation were significantly (P <
      0.01) higher than those in control subjects. There was no significant correlation
      between fecal alpha1-antitrypsin concentrations and time elapsed after the Fontan
      operation. The fecal alpha1-antitrypsin concentration increased significantly (P
      < 0.01) over periods of 14.7 to 19.8 months after the first measurement.
      CONCLUSION: The results show that enteric protein loss begins before the
      appearance of hypoproteinemia in patients after a modified Fontan operation, and
      that the measurement of fecal alpha1-antitrypsin concentrations in random stool
      samples is useful as an early indicator. To watch for the development of PLE
      after Fontan operation, it may be important to perform longitudinal follow-up
      examinations of enteric protein loss by measuring fecal alpha1-antitrypsin
      concentrations early in the postoperative period.

PMID- 14581801
TI  - Effects of highly purified eicosapentaenoic acid on erythrocyte fatty acid
      composition and leukocyte and colonic mucosa leukotriene B4 production in
      children with ulcerative colitis.
AB  - BACKGROUND: n-3 Polyunsaturated fatty acids (PUFAs) have been suggested as a
      treatment for ulcerative colitis (UC). However, the efficacy of n-3 PUFAs against
      UC has not been examined in children. Therefore, the authors investigated the
      effects of eicosapentaenoic acid (EPA) on fatty acid composition and leukotriene
      (LT) production in children with UC. METHODS: For 2 months the authors
      administered highly purified EPA ethyl ester (EPA-E) (1.8 g/d) to children with
      UC in remission. Colonic mucosal histology, fatty acid composition of erythrocyte
      membrane phospholipids, and LTB4 production by leukocytes and colonic mucosa were
      measured before and 2 months after the initiation of EPA-E treatment. RESULTS: No
      patients relapsed during the study period, and no significant differences were
      detected in laboratory findings obtained before and 2 months after the initiation
      of EPA-E ingestion. There were no significant differences in mucosal histologic
      scores before and 2 months after EPA-E treatment. The EPA levels in erythrocyte
      membranes 2 months after the initiation of EPA-E treatment were significantly
      higher than before treatment, but the other fatty acids showed no significant
      changes. LTB4 production by leukocytes and rectal mucosa after 2 months of EPA-E
      treatment was significantly lower than before treatment. CONCLUSION: EPA-E
      treatment increased the levels of EPA in erythrocytes and decreased LTB4 levels
      produced by leukocytes and colonic mucosa. To assess the concomitant clinical
      changes, we should examine the long-term effects of EPA-E ingestion on the
      maintenance of remission in children with UC.

PMID- 14581802
TI  - Hyperhomocystinemia in children with inflammatory bowel disease.
AB  - OBJECTIVES: Thromboembolism is a significant cause of morbidity and mortality in
      patients with inflammatory bowel disease (IBD). Plasma total homocysteine (tHcy)
      is a risk factor for vascular disease and has been implicated as a mediator of
      thromboembolic events in adults with IBD. The authors studied the link between
      tHcy and IBD in children, in whom associations may be clearer, and investigated
      associations with plasma von Willebrand factor antigen, a marker of vascular
      damage. METHODS: This cross-sectional study included 43 patients with IBD (27
      Crohn disease, 9 ulcerative colitis, and 7 indeterminate colitis) and 46 control
      subjects from a pediatric gastroenterology clinic. Plasma tHcy, plasma 5-methyl
      tetrahydrofolate, red cell folate, plasma vitamin B12, plasma von Willebrand
      factor antigen, and methylene tetrahydrofolate reductase (MTHFR) genotype (for
      the C677T mutation) were measured. RESULTS: Plasma tHcy concentrations were
      higher in children with IBD than in control subjects, when corrected for age (P <
      0.05), and plasma tHcy was negatively correlated with plasma 5 methyl
      tetrahydrofolate (P < 0.0005). Plasma 5 methyl tetrahydrofolate and age were the
      main predictors of plasma tHcy. Neither MTHFR genotype nor von Willebrand factor
      showed any association with any other measure, and there were no differences
      between children with IBD and control subjects. CONCLUSIONS: Elevated plasma tHcy
      is a consequence of IBD in children, probably mediated by poor folate status
      associated with diet or the pathophysiology of the disease.

PMID- 14581803
TI  - Pancreatitis in children.
AB  - OBJECTIVES: To determine the incidence, etiology and outcome of pancreatitis at a
      regional children's hospital. METHODS: Chart review of all patients with
      pancreatitis seen during a 6 year period at the Children's Hospital of Wisconsin.
      The diagnosis of pancreatitis required either a serum amylase or lipase >3 times
      normal or radiographic evidence of pancreatitis. RESULTS: Two hundred fourteen
      episodes of pancreatitis in 180 patients were documented. The most common
      etiologies were systemic disease (14%), trauma (14%), drug induced (12%), biliary
      tract disease (12%), infectious (8%), and idiopathic (8%), which made up 68% of
      the total cases. Eleven patients died, all from underlying systemic illnesses.
      The serum amylase and lipase were elevated in 82% and 83% of patients
      respectively. CONCLUSIONS: Pancreatitis is more common in children than
      previously thought. Upon careful assessment fewer cases were found to be
      idiopathic than in previous series. The outcome of pancreatitis depends on co
      morbid conditions.

PMID- 14581804
TI  - CagA antibodies as a marker of virulence in chilean patients with Helicobacter
      pylori infection.
AB  - BACKGROUND: The bacterial and host factors that influence the clinical outcomes
      of the Helicobacter pylori infection have not been fully identified. Cytotoxin
      associated gene product (CagA), one of the virulence factors, has been associated
      with a more aggressive form of infection. The authors studied the relationship
      between CagA status and clinical outcome in Chilean children and adults with H.
      pylori infection. METHODS: One hundred eighty consecutive patients undergoing
      upper gastrointestinal endoscopic analysis were enrolled after informed consent
      was obtained. Rapid urease test and histologic analysis were used to detect H.
      pylori infection. IgA and IgG antibodies to H. pylori whole cell antigen
      preparation and IgG antibodies to CagA were measured by enzyme-linked
      immunosorbent assay (ELISA). RESULTS: H. pylori infection was detected in 42% of
      the patients by biopsy or urease test and in 38% and 20% of patients by IgG and
      IgA antibodies, respectively. The prevalence of H. pylori either by the invasive
      or the serologic tests was directly related to patient age. Among patients with
      H. pylori, there was no significant association between age and prevalence of
      CagA. Nearly 70% of the patients with H. pylori and peptic ulcer disease had CagA
      positive strains. In contrast, only 49% of the patients with chronic gastritis
      alone had CagA-positive strains (P < 0.05). CONCLUSIONS: In Chile, patients
      infected with H. pylori have a proportion of CagA-positive strains similar to
      that reported in developed countries. CagA prevalence was not significantly
      different in adults and children infected with H. pylori, suggesting that
      variations in clinical outcome may be related to host immune or environmental
      factors.

PMID- 14581805
TI  - Assessment of the DQ heterodimer test in the diagnosis of celiac disease in the
      Canary Islands (Spain).
AB  - BACKGROUND: Celiac disease is a multifactorial disorder of the proximal small
      intestine associated with a permanent intolerance to gluten. The HLA
      DQ(alpha1*0501, beta1*02) heterodimer is strongly associated with this disease.
      MATERIALS AND METHODS: The authors studied a sample of 354 unrelated Caucasoid
      individuals: 118 patients with celiac disease and 236 control subjects. All
      patients and controls subjects were born in Gran Canaria (Canary Islands) at
      least two generations ago. The authors typed the HLA-DQA1 and DQB1 genes by DNA
      methods. The positive and negative predictive values of the test were studied.
      RESULTS: The mean age at diagnosis was 25.4 months, with a statistically
      significant proportion of females (64.4%, P < 0.002). For DQB1 gene, the
      susceptibility allele found was DQB1*02 (relative risk [RR] = 7.60, confidence
      interval [CI]: 5.35-10.78), whereas for the DQA1 gene, the susceptibility alleles
      found were DQA1*0501 (RR = 2.99, CI: 2.16-4.14) and DQA1*0201 (RR = 1.88, CI:
      1.25-2.82). The presence of the DQ(alpha1*0501, beta1*02) heterodimer was
      strongly associated with the disease (92.4% in the patients group vs. 21.6% in
      control subjects). HLA-DQ8 heterodimer was absent in the authors' patients.
      DQB1*02 homozygous subjects presented a higher relative risk for celiac disease.
      There was no correlation of DQB1*02 dosage with age at onset below 12 years of
      age or with gender distribution. Sensitivity, specificity, and the positive and
      negative predictive values of the test were 92.4%, 78.4%, 68.1%, and 95.4%,
      respectively. CONCLUSIONS: The presence of the DQ2 (DQA1*0501/DQB1*02)
      heterodimer is strongly associated with celiac disease in the population studied
      by the authors. The value of this test derives from its ability to exclude
      disease when a negative result occurs.

PMID- 14581806
TI  - Age and family history at presentation of pediatric inflammatory bowel disease.
AB  - OBJECTIVES: Young children are thought to be a unique subset of pediatric
      patients with inflammatory bowel disease (IBD). The authors' objective was to
      evaluate the differences in initial clinical presentation of young and older
      children with IBD and to determine whether a positive family history of IBD is
      associated with the age of presentation. METHODS: The authors reviewed the
      records of all patients with new diagnoses of Crohn disease (CD) and ulcerative
      colitis (UC) who presented between July 1996 and July 1999. Initial evaluation
      included assessment of growth parameters and laboratory values (hemoglobin
      concentration, platelet count, erythrocyte sedimentation rate, and serum
      albumin). Inquiry regarding a family history of IBD was made in every patient.
      RESULTS: There were 153 patients with new diagnoses (82 with CD and 71 with UC),
      with a mean age of 11.9 years (range, 16 months-18 years). The children with CD
      had a higher sedimentation rate and platelet count and a lower mean hemoglobin
      concentration and serum albumin at presentation than did children with UC. Body
      mass index (BMI) was significantly lower in patients with newly diagnosed CD than
      in those with UC. The only significant laboratory differences between patients
      younger than 11 years and those 11 years or older was a higher mean platelet
      count in patients with CD who were younger than 11 years. Of the younger patients
      with CD, 41.7% had a positive family history of IBD, which was significantly
      greater that that found in the older patients with CD. CONCLUSIONS: Except for
      higher platelet counts, a lower BMI, and a higher frequency of positive family
      history in young children with CD, there were no significant differences in the
      presentation of young children with IBD compared with older children.

PMID- 14581807
TI  - Impact of Helicobacter pylori infection on growth of children: a prospective
      cohort study.
AB  - OBJECTIVE: The aim of this study was to prospectively follow a cohort of children
      without Helicobacter pylori infection and to compare growth velocity in the
      children who become infected during follow-up with that of children who remained
      infection-free. METHODS: Three hundred forty-seven children in general good
      health, aged 12 to 60 months, who tested negative for H. pylori by the 13C-urea
      breath test, from three daycare centers in a lower-middle class borough of Cali,
      Colombia, were monitored for 2.5 years. Anthropometric measurements were
      performed every 2 months and breath tests every 4 months. Linear mixed models
      were used to analyze growth velocity in relation to onset of H. pylori infection.
      RESULTS: One hundred five (30.3%) children who were uninfected at the start of
      the study became infected during follow-up. Growth velocity in infected children
      was reduced by 0.042 +/- 0.014 cm/mo (P = 0.003) (approximately 0.5 cm/yr) after
      adjusting for age. The rate of deceleration in growth velocity was relatively
      constant over time. CONCLUSIONS: Among these lower-middle class children aged 12
      to 60 months from a population with high prevalence of H. pylori infection, a new
      and sustained infection was followed by significant growth retardation.

PMID- 14581808
TI  - Sclerosing cholangitis associated with trichosporon infection and natural killer
      cell deficiency in an 8-year-old girl:.

PMID- 14581809
TI  - Metastatic hepatocellular carcinoma in a patient with niemann-pick disease, type
      C.

PMID- 14581810
TI  - A novel missense mutation of the bilirubin UDP-glucuronosyltransferase gene in a
      Turkish patient with Crigler-Najjar syndrome type 1.

PMID- 14581811
TI  - Acute myeloid leukemia presenting as non-neutropenic colitis in an infant.

PMID- 14581812
TI  - Is pain a vital sign?

PMID- 14581813
TI  - Zinc supplementation: yea or nay?

PMID- 14581814
TI  - 5 questions--and answers--about off-loading.

PMID- 14581815
TI  - Herpesvirus infections and herpetic wounds.

PMID- 14581816
TI  - Hyperbaric oxygen therapy 2003 Medicare coverage decision.

PMID- 14581817
TI  - Orchestrating wound healing: assessing and preparing the wound bed.
AB  - PURPOSE: To provide an overview of the steps needed to prepare the wound bed for
      healing. TARGET AUDIENCE: This continuing-education activity is intended for
      physicians and nurses with an interest in learning about the process for
      preparing the wound bed for healing. LEARNING OBJECTIVES: After reading the
      article and taking the test, the participant will be able to: 1. Describe the
      anatomy and physiology of the skin. 2. Describe the wound healing process, the
      local and systemic factors that may impair healing, and the parameters that
      assess the wound status. 3. Describe the steps in the process to prepare the
      wound bed for healing.

PMID- 14581818
TI  - The measurement of leg ulcer pain: identification and appraisal of pain
      assessment tools.
AB  - OBJECTIVE: To identify and compare the psychometric, clinical sensibility, and
      pain-specific properties of leg ulcer pain assessment tools for use as a guide
      for clinicians and researchers. DESIGN: Pain assessment tools were selected for
      appraisal based on 4 inclusion criteria: (1) designed specifically to measure
      either quality and/or intensity of pain, (2) used in at least 2 different
      diseases and/or pain-inducing interventions in adults, (3) generic, and (4)
      patient self-reporting. The tools were appraised against psychometric properties,
      clinical sensibility attributes, and pain-specific issues. Two reviewers
      independently reviewed each abstract, with a third reviewer resolving any
      disagreements. Then the first 2 reviewers independently assessed the selected
      tools using the predetermined appraisal criteria. RESULTS: Of 54 identified pain
      assessment tools, 5 (the pain ruler, the numerical rating scale, the visual
      analogue scale, the verbal descriptor scale, and the short-form McGill Pain
      Questionnaire) met the inclusion criteria. Each tool met the appraisal criteria
      to varying degrees. CONCLUSIONS: The use of a pain assessment tool to measure leg
      ulcer pain is recommended. Clinicians must decide independently which factors are
      most important when selecting a tool. Although a specific pain assessment
      approach cannot yet be recommended, a 2-step pain assessment process is most
      practical. To optimize pain management, further study is needed to ensure that
      leg ulcer pain is accurately and reliably assessed.

PMID- 14581819
TI  - How to prevent and manage skin tears.

PMID- 14581820
TI  - Hertig and beyond: a systematic and practical approach to the endometrial biopsy.
AB  - Evaluation of the endometrial biopsy is a challenge to practicing pathologists,
      largely due to the wide range of morphologic patterns resulting from both normal
      and abnormal cyclic changes, exogenous hormones, infections, and intrauterine
      tumors. Successfully addressing these challenges requires that the practitioner
      (i) understand the clinical questions being asked, (ii) have a realistic
      expectation for answering these questions, and (iii) have a systematic approach
      to resolving these questions in the context of these expectations. The approach
      outlined begins with the subdividing of women with endometrial alterations into
      three general categories: (i) women in their fourth decade undergoing evaluation
      for infertility, (ii) women in their fifth decade who experience abnormal uterine
      bleeding, and (iii) women in their sixth decade and beyond who experience
      postmenopausal bleeding. The clinical expectations for each group are unique, as
      are the morphologic patterns most commonly encountered. Algorithms for the
      laboratory management of cyclic changes, dysfunctional bleeding, and mixed
      pattern endometria are provided, as are pitfalls in interpretation and exclusion
      of neoplasia.

PMID- 14581821
TI  - Pathology of food-borne infectious diseases of the gastrointestinal tract: an
      update.
AB  - Although naturally occurring food-borne pathogens cause more than 76 million
      illnesses, 325,000 hospitalizations, and 5000 deaths annually in the United
      States, many more infections are unrecognized and unreported. In addition, mass
      production and distribution of food, on a global rather than a local scale, make
      it possible for localized instances of contamination to spread quickly to other
      states, provinces, and countries. Infectious organisms are often recovered by
      microbiological methods, but surgical pathologists may play a very valuable role
      in diagnosis. This review will focus on the diagnosis of food-borne infectious
      diseases of the gastrointestinal tract, including those that mimic other
      inflammatory conditions of the gut (such as ischemia or idiopathic inflammatory
      bowel disease); available diagnostic methods; and gastrointestinal infectious
      processes that pathologists should be aware of in terms of potential biologic
      weapons threats.

PMID- 14581822
TI  - Ocular surface impression cytology.
AB  - Impression cytology, either using cellulose acetate strips or the Biopore
      membrane device, is a simple, noninvasive technique that aids in the diagnosis of
      several disorders of the ocular surface. These disorders include ocular surface
      squamous neoplasia, dry eye syndrome, limbal stem-cell deficiency, specific viral
      infections, vitamin A deficiency, allergic disorders, conjunctival melanosis, and
      malignant melanoma. Another advantage is the preservation of limbal stem cells,
      which occur in the basal layer of the limbal epithelium and are responsible for
      renewal of the corneal epithelium. The Biopore membrane device is particularly
      user friendly, with little expertise required and adequate specimens obtained in
      a very high percentage of cases. The most common applications in diagnostic
      ocular pathology are:(i) primary diagnosis and follow-up of ocular surface
      squamous neoplasia, including after therapy with topical mitomycin C. The
      sensitivity is high (78-87%); and (ii) dry eye syndrome where squamous metaplasia
      and/ or hyperkeratosis are noted. Certain limitations of the technique for
      diagnosis of squamous neoplasia include the fact that dysplasias are often
      keratinizing and may yield very few or even no dysplastic cells with impression
      cytology. Secondly, no definite cytologic criteria reliably distinguish invasive
      SCC of ocular surface from in situ disease. Other applications include the rapid
      specific diagnosis of ocular surface infections with herpes simplex, adeno-, and
      varicella zoster viruses. Impression cytology samples may also be used to obtain
      mRNA, cells for phenotyping by flow cytometry, and proteins for Western blotting
      for research studies.

PMID- 14581823
TI  - Gene-expression profiles and breast-cancer prognosis.

PMID- 14581824
TI  - A guest editorial: shoulder dystocia and posture for birth: a history lesson.

PMID- 14581825
TI  - Pregnancy in a persistent vegetative state: case report, comparison to brain
      death, and review of the literature.
AB  - Severe maternal neurologic injury during pregnancy has the potential for fetal
      demise without advanced critical care support to the mother. Brain death is the
      unequivocal and irreversible loss of total brain function, whereas patients in a
      vegetative state, by contrast, have preserved brain stem function but lack
      cerebral function. They can appear to be awake, have sleep-wake cycles, be
      capable of swallowing, and have normal respiratory control, but there are no
      purposeful interactions. These conditions have different maternal prognoses, but
      both have resulted in near-normal neonatal outcomes with long latencies from
      maternal injury to delivery in previously published cases. This article compares
      and contrasts the 11 cases of brain death with 15 cases of persistent vegetative
      state in pregnancy. We found that the mean latency between maternal brain injury
      and delivery was significantly shorter in the brain-dead patients as compared
      with those in a vegetative state (46 days vs. 124 days, P </=.001).
      Correspondingly, the gestational ages at delivery (29.7 weeks vs. 33.2 weeks, P
      </=.01) and the birth weights (1380 g vs. 2145 g, P </=.01) were shorter in
      duration and smaller in size in the brain-dead group. We also present a case of
      persistent vegetative state in pregnancy at our institution with both maternal
      and neonatal death in the context of previously published literature with a focus
      on obstetric and ethical management. We hope this information will help elucidate
      the issues for providers confronted with these unique and challenging cases.
      TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING
      OBJECTIVES: After completion of this article, the reader should be able to state
      the difference between coma, persistent vegetative state and brain death, to
      describe the neurologic aspects of a patient in a persistent vegetative state,
      and to list the fetal effects of maternal brain injury.

PMID- 14581826
TI  - Quality-of-life issues in patients with ovarian cancer and their caregivers: a
      review.
AB  - Significant progress has been made towards the treatment of ovarian cancer
      resulting in longer median survival despite a persistent low cure rate.
      Relatively few studies have examined the impact of the cancer and its treatment
      on the patients and their caregivers due to the difficulty in the definition and
      measurement of the Quality of Life (QOL) concept. A review of the literature
      revealed significant alterations in the quality of life of ovarian cancer
      patients during treatment and long term follow ups. For the caregivers, it is
      important for health care providers to realize that: 1) caregivers are being
      asked to assume an increasing number of complex care giving tasks at home, 2)
      there exists a high proportion of unmet caregiver needs, 3) the care giving
      experience includes both positive and negative elements and, 4) perception of
      caregivers' burden is positively linked to negative reactions to care giving.
      Supportive programs for patients and caregivers should be designed with these
      needs in mind. Future research should study the best way to incorporate results
      of quality of life assessments into routine treatment decision-making. TARGET
      AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES:
      After completion of this article, the reader should be able to outline the
      current data on QOL issues in patients with ovarian cancer, and to describe
      potential working definitions of QOL.

PMID- 14581827
TI  - Gestational diabetes: a field of controversy.
AB  - Many clinicians in the United States routinely screen all pregnant women in their
      practices for gestational diabetes. Recently, the US Preventive Services Task
      Force re-emphasized that such screening is not supported by rigorous scientific
      evidence. Recommendations for diagnosis and management are based on an even
      scantier scientific foundation. Although this review questions several aspects of
      current dogma, it, too, is based on the frequently flawed existing data. It is
      surprising how, in spite of an abundance of published information on the subject,
      we continue to be ignorant of the real benefits of the widespread practice of
      screening and treating for gestational diabetes. The authors hope that the
      results of a randomized clinical trial, now in progress, will help to resolve
      some of the controversies surrounding gestational diabetes. TARGET AUDIENCE:
      Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After
      completion of this article, the reader should be able to describe the controversy
      surrounding the significance of gestational diabetes, to break down the data
      regarding the efficacy of screening for gestational diabetes, and to outline
      potential treatment options for gestational diabetes.

PMID- 14581828
TI  - Sonohysterography: a valuable tool in evaluating the female pelvis.
AB  - A number of medical conditions, including abnormal uterine bleeding, endometrial
      cancer, monitoring tamoxifen therapy, infertility, and recurrent abortion,
      warrant investigation of the female genital tract. Diagnostic studies including
      hysterosalpingogram, ultrasound, and sonohysterography have proved useful in the
      investigation of these gynecologic conditions. This article discusses each of
      these tests with particular emphasis on sonohysterography and their current and
      potential contributions in both diagnostic and therapeutic applications. The
      utility of each as well as their comparative value to each other and existing
      gold standards is reviewed. TARGET AUDIENCE: Obstetricians & Gynecologists,
      Family Physicians. LEARNING OBJECTIVES: After completion of this article, the
      reader should be able to outline the current screening methods for uterine cavity
      and pelvic abnormalities, to list the advantages of sonohysterography, and to
      describe the clinical situations where sonohysterography can be used.

PMID- 14581829
TI  - Chemical and biological terrorism preparedness for staff development specialists.
AB  - Staff development specialists must adapt orientation and continuing/life-long
      learning educational programs to provide nursing staff with the knowledge and
      skills required to respond to a biological or chemical terrorist attack. The
      integration of accurate, reliable, and timely information into staff development
      programs will contribute to the advancement of a national nursing workforce
      adequately prepared to respond to a major public health event resulting from the
      intentional use of biological and chemical weapons.

PMID- 14581830
TI  - Concept mapping as a critical thinking tool for nurse educators.
AB  - Nursing educators must use teaching strategies designed to develop critical
      thinkers. Concept mapping helps fulfill this goal. Staff development instructors
      should continue the development of new nurse critical thinking skills using
      concept maps in a variety of ways.

PMID- 14581831
TI  - The Nursing Assistant to Licensed Practical Nurse Program: a collaborative career
      ladder experience.
AB  - The Department of Veterans Affairs (VA) is committed to providing cost-effective,
      quality care to veterans. Given an aging veteran population and common, multiple
      co-morbid illnesses, the needs of the typical patient cared for within the VA
      system are complex. Thus, caregivers meeting these needs require additional
      nursing education. To ensure the staff will have the skills necessary to care for
      patients experiencing more complex illnesses, the Battle Creek VA Medical Center
      (VAMC) designed a program giving experienced nursing assistants the opportunity
      to enroll in a nursing program leading to practical nurse licensure. The Nursing
      Assistant to Licensed Practical Nurse Program has been established by developing
      a collaborative agreement with an affiliating educational institution, defining
      the selection criteria, helping to prepare funding requests, developing a
      mentoring program, coordinating with Human Resources and Fiscal Services, and
      outlining the service obligation. After the first year of this program, the VAMC
      and the academic institution consider it a successful collaborative effort.

PMID- 14581832
TI  - Setting valid cut-off scores for competency.
AB  - Results of competency, or certification, tests can have serious consequences for
      individuals tested, for employers, and for the public. However, the validity of
      testing outcomes depends not only on the validity of the test's content but also
      on the validity of the score selected as the passing, or cut-off, score. This
      article describes procedures and techniques for use by staff development
      professionals to ensure systematic, rational, and defensible cut-off scores for
      competency tests.

PMID- 14581833
TI  - Ten tips to help learning.
AB  - Facilitating learning for nurses in the healthcare environment is challenging.
      These 10 tips are designed to help staff development educators explore ways to
      enhance learning. The emphasis is on active involvement of the learner, with the
      educator as facilitator rather than "teacher." Tips are evidence-based, specific,
      and to the point, with suggestions for implementation.

PMID- 14581834
TI  - Healthcare information systems: education lessons learned.
AB  - The educator is a key person during the implementation of a new healthcare
      computer system or a new software program. Computers require teamwork across
      departmental lines and flexibility in instructional approach. The authors share
      their experiences as educators at the San Francisco VA during the initiation of
      several new computer software packages. They examine the issues involved in this
      type of training and share the lessons learned.

PMID- 14581835
TI  - Effective resuscitation by nurses: perceived barriers and needs.
AB  - Nurses work in a variety of clinical settings. Some of these areas involve care
      of patients with acute illnesses while others do not. No matter in which setting
      a nurse works, the possibility exists that he or she will participate in the
      resuscitation of a patient. When patients face a life-threatening event such as
      cardiopulmonary arrest, they rely on the competence and skills of healthcare
      professionals. Because nurses are often the healthcare providers closest to the
      bedside and the first to respond to patients' needs, their knowledge and skills
      need to be optimal and their performance proficient.

PMID- 14581836
TI  - Nursing and personal care cannot be distinguished.

PMID- 14581837
TI  - Life in the COPD straitjacket: improving lives of sufferers.

PMID- 14581838
TI  - Abuse of patient with Alzheimer's disease in a nursing home.

PMID- 14581840
TI  - Results of a fatigue management programme in multiple sclerosis.
AB  - Fatigue in patients with multiple sclerosis (MS) is a complex symptom that is
      notoriously difficult to treat, not least because it is extremely subjective and
      is experienced differently by each patient. Owing to the prevalence of this
      symptom, most patients with MS who are seen in outpatient settings complain of
      fatigue and experience the disabling effect it can have upon day-to-day living.
      Managing and treating this symptom is a challenge, although there is some
      evidence that applying fatigue management principles can potentially reduce the
      debilitating effect fatigue has on patients (Welham, 1995). This article reviews
      the evidence base surrounding the management and treatment of fatigue that is
      applied in clinical practice. It describes the fatigue management programme that
      had been introduced for people with MS at the authors' workplace, and evaluated
      whether applying fatigue management principles can make a difference to people's
      ability to self-care. The effect this symptom has upon people's quality of life
      will also be explored.

PMID- 14581839
TI  - Patients' quality of life and clean intermittent self-catheterization.
AB  - This article examines the available literature surrounding the procedure of clean
      intermittent self-catheterization (CISC) and its impact on patients' quality of
      life. Many articles have been written about, and much research has been carried
      out into, the practicalities of performing CISC regarding dexterity, disability,
      etc, and its advantages and disadvantages related to infection rates and
      complications. However, there appear to be very few articles addressing the day
      to-day problems that having to perform CISC presents to patients. While many
      articles do acknowledge that CISC improved patients' quality of life, very few go
      on to identify and discuss the daily life activities that are impacted upon by
      having to perform the procedure. There is a need for further research from
      patients' perspectives: to identify the issues that they have in living with this
      inconvenience and in order for carers to understand fully the implications of
      CISC on a patient's quality of life. With this insight, carers will be better
      armed to help patients overcome their fears and be more supportive in the ongoing
      care of the patient. Non-compliance is the main reason for patients' inability to
      perform CISC and with a better understanding of the problems, carers will be able
      to give practical help and support.

PMID- 14581841
TI  - Ward nutrition coordinators to improve patient nutrition in hospital.
AB  - It is important that patients receive adequate nutrition while in hospital.
      Reports and research over the past 10 years have highlighted the problems in the
      NHS of managing the nutritional needs of patients (King's Fund, 1992; McWhirter
      and Pennington, 1994; Edington et al, 2000). This article describes a successful
      pilot study addressing nutrition at the ward level. It resulted from a
      multidisciplinary team forming to share their specific nutritional concerns;
      through creative thinking they devised a new role of nutrition coordinator. In
      the study a healthcare assistant was used from the existing ward establishment
      and given one-week intensive multidisciplinary induction before commencing the
      role in the wards. The main focus of the role was to facilitate, rather than
      undertake, the nutritional care of patients throughout their stay. Following a 6
      month trial, the role demonstrated a significant impact on nutritional screening,
      nutritional service, patients' perceptions of their nutritional care, and staff
      satisfaction.

PMID- 14581842
TI  - A history of diabetes: from antiquity to discovering insulin.
AB  - This article, the first of a three-part series, gives a historical account of
      events for diabetes, dating from antiquity and its first recording in the Ebers
      Papyrus--an Egyptian document circa 1500 BC. This article describes initial
      thoughts that diabetes was linked to an alimentary complaint, and concludes with
      the discovery of it being a chronic systemic disease. It highlights the
      discoveries and also includes details of the failed attempts to locate the cause
      and identify a solution to the ancient mysterious disease which became known to
      all as diabetes mellitus. Early remedies and treatments are included. The article
      tells how for many centuries individuals suffered from the debilitating complaint
      with very little offered in terms of treatment or relief. Eventually the pancreas
      was identified as the causative organ and, some time later, animal
      experimentation resulted in the abstraction of the substance insulin. The article
      concludes with Frederick Banting and John Macleod being awarded the Nobel Prize
      in 1923 for their revolutionary discovery of insulin.

PMID- 14581843
TI  - Degree vs diploma education: increased value to practice.
AB  - Graduate education for nursing and midwifery has been debated for some years,
      with current opinion in favour of at least an increase in degree provision
      (Nursing and Midwifery Council (NMC), 1999). The professions as well as consumers
      and purchasers of nursing and midwifery education need to be sure, however, that
      they are getting "added value" with the graduate practitioner. Educationalists
      identify "critical thinking" as the level that distinguishes diploma from
      graduate preparation. This article intends to clarify whether academic
      achievements are restricted to the theoretical aspects of the award or whether a
      degree adds value to clinical practice. The study design was an experimental case
      control cross-sectional survey carried out on samples of nursing and midwifery
      graduates and diplomates. The graduates were grouped as experimental cases, while
      the diplomates were controls. A measurement tool of 42 items covering a range of
      attributes and skills was employed in the study to provide a rating score for
      individual samples. Statistical analysis was carried out and showed that the
      scores from graduates were significantly different from the diplomates,
      indicating that there are genuine differences between the graduates and
      diplomates. Furthermore, from discriminant analysis of item scores, it appeared
      that the graduates' overall item scores were higher than the diplomates as
      indicated by the centroid of the functions being positive for the graduates and
      negative for the diplomats. The evidence from this study seems to support current
      thinking that a degree adds value to practice.

PMID- 14581844
TI  - Medicinal products and consent by mentally capacitated patients.
AB  - Case scenario: Roy Dawes has been diagnosed as having diabetes, but is not
      prepared to keep to the necessary diet which should have been able to control his
      condition. In particular he is a heavy drinker. He was therefore advised that he
      would require insulin and regular blood testing. He failed to comply with this
      regimen and the community nurse wondered if he could be compelled to have his
      medication. What is the law?

PMID- 14581845
TI  - Nurses must protect vulnerable older people.

PMID- 14581846
TI  - Not just the same old song, on the radio.

PMID- 14581847
TI  - Providing adequate treatment for children with nocturnal enuresis.
AB  - Nocturnal enuresis is the most common urological problem in children. With
      increasing age and persistence of enuresis, children may experience psychological
      problems. Active treatment is therefore required not only to achieve dryness but
      also to prevent and treat such an experience. Although nocturnal enuresis has
      multiple causes, in recent years emphasis has focused on three main causes: lack
      of arousal, lack of antidiuretic hormone secretion and lack of bladder stability.
      This article stresses the importance of applying a specific treatment based on
      this "three system approach" for every child presenting with enuresis.

PMID- 14581848
TI  - A literature review of the public health roles of health visitors and school
      nurses.
AB  - This paper describes a two-stage review relating to the family-centred public
      health role of health visitors and the child-centred public health role of school
      nurses. During the first stage, literature was searched using CINAHL and Medline
      databases and two models were used to frame the literature analysis. The findings
      of this analysis were, however, disappointing. Although many policy documents
      advocate development of the family-centred public health role of health visitors
      and the child-centred public health role of school nurses, there was no
      overwhelming evidence of reports of these approaches in health visiting and
      school nursing practice. The second stage of the review comprised a content
      analysis of West Midlands community trusts' strategic development plans.
      Seventeen plans were analysed. Of these, only two were 'formal' plans, the
      remainder being fragmented documentation related to plans for the development of
      health visiting and school nursing services. It may be concluded from the
      analysis that NHS trusts are beginning to adopt ideas from the rhetoric of
      national policy documents. Additionally, public health practice initiatives form
      an integrated part of most of the trust strategic development plans that the
      researchers examined.

PMID- 14581849
TI  - The right to refuse life-saving treatment: who decides?
AB  - District nurse Alison has a patient, Nigel, who has type 1 diabetes that remains
      unstable. Nigel's eyesight has deteriorated, his sexual function has dramatically
      reduced and he has now developed an infection in his right foot which requires
      immediate treatment. Nigel refuses the treatment and any further insulin
      declaring he would rather die than live the rest of his life like this. The GP
      says he will have Nigel detained under the Mental Health Act for assessment and
      enforced treatment, as his decision to refuse treatment amounts to suicide.
      Alison is concerned that Nigel will die without treatment, but also worries that
      to force treatment would be unlawful.

PMID- 14581850
TI  - Does the use of pacifiers shorten breastfeeding duration in infants?
AB  - Breastfeeding has a number of benefits for both mother and baby, which appear to
      increase with longer duration of breastfeeding. The use of pacifiers has been
      negatively associated with shortened breastfeeding duration. The aim of this
      review was to determine whether the use of pacifiers actually shortens
      breastfeeding duration in infants. The Cochrane library, Medline, CINAHL and
      Embase databases were searched for systematic reviews, randomized controlled
      trials and cohort studies examining the effect of pacifier use on breastfeeding
      duration. After applying appropriate inclusion criteria only two cohort studies
      were identified. In one the overall breastfeeding duration was longer in non
      pacifier-using infants compared to those given pacifiers (10 months vs. 7.5
      months). The mean breastfeeding duration in children who were given pacifiers
      before 6 weeks of age was 168.5 days compared to 196.0 days for children who had
      a pacifier introduced later or never. However, there is no evidence to suggest
      any effect from occasional pacifier use, and it remains unclear whether pacifiers
      are an independent causal factor for reducing breastfeeding duration in infants.

PMID- 14581851
TI  - So you want to do research? 3. An introduction to qualitative methods.
AB  - This article describes some of the key issues in the use of qualitative research
      methods. Starting with a description of what qualitative research is and
      outlining some of the distinguishing features between quantitative and
      qualitative research, examples of the type of setting where qualitative research
      can be applied are provided. Methods of collecting information through in-depth
      interviews and group discussions are discussed in some detail, including issues
      around sampling and recruitment, the use of topic guides and techniques to
      encourage participants to talk openly. An overview on the analysis of qualitative
      data discusses aspects on data reduction, display and drawing conclusions from
      the data. Approaches to ensuring rigour in the collection, analysis and reporting
      of qualitative research are discussed and the concepts of credibility,
      transferability, dependability and confirmability are described. Finally,
      guidelines for the reporting of qualitative research are outlined and the need to
      write for a particular audience is discussed.

PMID- 14581852
TI  - BagBath: the value of simplistic care in the community.
AB  - Community nurses need to manage and embrace both the clinical and public health
      needs of their clients, which requires both ingenuity and improvisation. Although
      the community care environment is very different to hospital care, like all
      professionals, community nurses must live with the inevitability of change. The
      modern nurse must offer high-quality patient care and should be constantly
      striving for cost-effective methods of providing that care. In this product
      focus, the cost-effectiveness and infection control potential of the prevalent
      practice of "bed bathing" is compared with the new concept of BagBath (Westholme
      Ltd). BagBath is a quick-drying one-step bed bath product offered as an
      alternative to the bowl of water, soap, flannel and towel.

PMID- 14581853
TI  - Are health service targets doing their job?

PMID- 14581854
TI  - Review of recommendations on cervical cancer screening in the European Union.
AB  - In 2000 the European Commission Advisory Committee on Cancer Prevention published
      a position paper on cancer screening with recommendations. This followed working
      party deliberations in 1998 and conference discussion in 1999. Scientific
      advances, particularly in knowledge about the relationship of HPV and cervical
      cancer and political developments with the enlargement of the European Union,
      mean that the position paper and recommendations may shortly need revising in the
      light of changed circumstances.

PMID- 14581855
TI  - The ovarian surface epithelium: simple source of a complex disease.
AB  - The ovarian surface epithelium (OSE) is thought to be the origin of most ovarian
      cancers in humans. OSE is a single cell layer of squamous or cuboidal cells on
      the surface of ovaries. In contrast to its relatively simple structure, it gives
      rise to a highly complex group of neoplasms, the epithelial ovarian carcinomas.
      Thus, in this review, we summarize the development and the main characteristics
      of normal adult OSE with emphasis on those properties that might contribute to
      its propensity to undergo neoplastic progression. Secondly, a brief comparison of
      the biology and endocrinology of normal and neoplastic OSE is being described to
      understand the mechanisms in the transformation of normal OSE to its neoplastic
      counterparts. Lastly, recent advances in experimental approaches including in
      vitro and in vivo models that have contributed to our understanding of the nature
      of epithelial ovarian cancers are being briefly explored.

PMID- 14581856
TI  - Diagnosis and treatment of epithelial ovarian cancer.
AB  - Epithelial ovarian cancer is a highly curable disease when diagnosed in an early
      stage. Unfortunately, treatment for advanced stage disease is mainly palliative.
      This article will review new developments in the diagnosis of ovarian cancer
      involving diagnostic imaging techniques and circulating tumor markers. It will
      discuss the current role of surgery in the treatment of the disease, including
      cytoreductive surgery, interval debulking surgery and surgery following
      neoadjuvant chemotherapy. It will evaluate the currently available chemotherapy
      treatments for epithelial ovarian cancers and present new developments in the
      medical management of this disease.

PMID- 14581857
TI  - [Tumor markers in epithelial ovarian cancer].
AB  - Many circulating markers are already in clinical practice and in experimental use
      for the diagnosis, therapeutic monitoring, and in the follow-up of ovarian
      cancer. The cancer antigen-125 (CA-125) has shown to be useful in epithelial
      ovarian cancer, but its specificity is too low for the test to be used as a
      primary screening technique in early stage and particularly in premenopausal
      women. In the last few years, several studies have focused on using the serial
      measurement of complementary serum markers to improve the positive predictive
      value and diagnostic accuracy. The main problem is that the different cellular
      lines express these markers in a very variable way.

PMID- 14581858
TI  - Peritoneal fluid environment in endometriosis. Clinicopathological implications.
AB  - Endometriosis is a puzzling disorder with obscure pathogenesis. The objective of
      this review was to evaluate the complex role of peritoneal fluid in the
      etiopathogenesis of endometriosis. Several studies suggest that peritoneal fluid
      is a key inflammatory environment associated with endometriosis. Many active
      substances (cytokines, growth factors, hormones and oxidative stress parameters)
      have been identified in endometriosis patients at different stages of the
      disease. Inflammatory mediators may be involved in the endometriosis associated
      infertility and possibly pain. Furthermore, these mediators may represent a non
      surgical method for diagnosing endometriosis. Better understanding of the
      mechanism of cytokines, growth factor and reactive oxygen species production and
      detoxification and further investigation of their effects on the peritoneal fluid
      environment are essential to obtain new insight into this disease and eventually
      develop novel diagnostic and therapeutic remedies.

PMID- 14581859
TI  - [Second trimester termination of pregnancy with gemeprost: a review of 306
      cases].
AB  - AIM: Prostaglandin analogues provide an effective method for induction of
      abortion in the second trimester of pregnancy. The clinical outcome and the risk
      of complications were evaluated in a group of women having a medical termination
      of pregnancy with gemeprost. METHODS: Three-hundred and six women undergoing
      second trimester termination of pregnancy, between January 1998 and July 2002 in
      our center, were studied. All women were given 1 mg vaginal gemeprost every 3 h
      up to a maximum of 3 doses in the first 24 hours. If the abortion did not occur
      within the first 24 hours after initiation of treatment, they were given a 2(nd)
      course of gemeprost. Outcome measures included failure of the 1st course of
      gemeprost, length of hospital stay after expulsion of conceptus, heavy blood loss
      with or without necessity of uterine packing or blood transfusion, and failure of
      induction. RESULTS: There was a significant difference, with better results in
      women with previous deliveries (vaginal or abdominal), as to the failure to abort
      after the 1(st) course of PG (P<0.01). Length of hospital stay, complications and
      failure of induction were independent from parity. Twelve (3.9%) women failed to
      abort with gemeprost and required other methods for abortion. CONCLUSIONS: The
      study confirms the efficacy of gemeprost for mid-trimester termination of
      pregnancy, although it is a risky and costly procedure, requiring hospitalisation
      and is associated with higher complication rate than the first trimester surgical
      abortion.

PMID- 14581860
TI  - [Monitoring of pregnancy complicated by maternal-fetal isoimmunization. A
      comparison between two clinical protocols].
AB  - AIM: Invasive techniques such as amniocentesis and cordocentesis are used for the
      diagnosis and treatment of fetus at risk for anemia due to maternal red-cell
      alloimmunization. The purpose of this study was to determine the value of non
      invasive measurements of the peak velocity middle cerebral artery in the fetus
      (PVMCA) for the diagnosis of fetal anemia. METHODS: From 1996 to September 2002,
      we studied 23 pregnancies with anti D title >1:32. In the 1(st) group of 11 women
      (from 1996 to 1999) fetal anemia was detected by invasive techniques
      (amniocentesis and cordocentesis). In the 2(nd) group of 12 women (from 1999 to
      2002) fetal anemia was suspected on the basis of PVMCA. When PVMCA was
      significantly increased, cordocentesis was performed in order to rule out fetal
      anemia and to provide in utero transfusions. RESULTS: In the 1(st) period we
      performed 23 invasive techniques (7 amniocentesis and 16 cordocentesis) in 11
      women, but we identified fetal anemia only in 4 cases. In the 2(nd) period we
      performed only 2 cordocentesis in women in which PVMCA was increased; the blood
      sampling confirmed fetal anemia in both cases. CONCLUSION: PVMCA and fetal
      hematocrit are highly significantly correlated: high values of PVMCA are
      associated with fetal anemia. Doppler velocity of PVMCA is related to fetal
      anemia with positive predictive value 100% and negative predictive value 100%.
      The middle cerebral artery blood velocity is a non invasive technique for
      detecting anemia in pregnancies complicated by alloimmunization.

PMID- 14581861
TI  - Alcohol sclerosis of endometriomas after ultrasound-guided aspiration.
AB  - AIM: We investigate the possibility to use ultrasound-guided aspiration and
      alcohol sclerosis in patients with endometrioma. METHODS: Ten patients with
      endometriotic ovarian cysts, mean diameter <70 mm, CA125 <35 UI, persistence of
      cyst after medical therapy and refusal of surgical therapy have been studied. The
      patients were submitted to ultrasound-guided aspiration of endometriomas. Fifty
      per cent of aspirated fluid was replaced with pure ethanol, which was left in
      situ for 10 to 20 minutes. No medical therapy was employed after aspiration and
      ethanol treatment. RESULTS: In 9 patients no recurrence was observed at
      ultrasound after 21.2+/-6.62 months of follow-up. In 1 case only, after 6 months,
      a recurrence of the endometrioma in the same site was observed. CONCLUSION:
      Ultrasound-guided alcoholic sclerotherapy of the endometriotic ovarian cysts is
      effective and safe. We speculate that this procedure could be indicated in
      patients refusing standard surgical therapy.

PMID- 14581862
TI  - [Pentalogy of Cantrell: first trimester prenatal diagnosis and association with
      multicistic dysplastic kidney].
AB  - Pentalogy of Cantrell is a rare congenital anomaly consisting of the following
      features: 1) midline supraumbilical abdominal wall defects; 2) deficiency of the
      anterior diaphragm; 3) defects in the diaphragmatic pericardium; 4) defects of
      the lower sternum; 5) congenital intracardiac defects. We report 3 cases of
      pentalogy of Cantrell diagnosed respectively at 13, 18 and 24 weeks of gestation.
      In case 1 Cantrell's pentalogy was diagnosed during the 1(st) trimester. Case 2
      revealed the coexistence of cystic hygroma. Case 3 showed an association with
      dysplastic left kidney and mild pyelectasis of the right kidney. Our results
      confirm the possibility of an early detection of Cantrell's pentalogy and reveal
      the possibility of associations with other pathological findings.

PMID- 14581863
TI  - [Controlled release vaginal dinoprostone for the induction of labour].
AB  - AIM: To study the efficacy and safety of controlled release dinoprostone (PGE2)
      for the induction of labour. METHODS: From March 2001 to August 2002, a total of
      173 patients hospitalized for postdate pregnancy, maternal hypertension,
      intrauterine delayed growth, reduction of amniotic fluid, were studied. In 33 of
      these patients, a hydrogel strip containing 10 mg dinoprostone, inserted into the
      posterior fornix of the vagina and release PGE2 at constant rate of 0.3-0.4 mg/h
      was used. RESULTS: Indications for induction, mode and time of delivery,
      maternal, fetal and neonatal parameters anomalies are evaluated. In 23 patients
      dinoprostone was used for postdate pregnancy, in 4 for maternal hypertension, in
      4 for oligohydramnios and in 2 for intrauterine delayed growth. In 2 cases, the
      vaginal insert was removed for hyperstimulation in 1 case and for abnormal fetal
      heart rate in the other case. After vaginal delivery, Apgar scores and umbilical
      artery pH values were evaluated without anomalies. Vaginal delivery within 24
      hours occurred in 51.6% of patients and medium time to delivery was 17.5
      (nulliparous) and 12.3 (multiparous) hours. Only one case of uterine
      hyperstimulation to PGE2 was recorded, and the induction was suspended. The
      cesarean section rate was 12% and vaginal delivery after 24 hours was 38.7%.
      CONCLUSION: The continuous release of PGE2 from the vaginal insert permits a
      controlled and safe induction of labour, minimal risk of hyperstimulation, fast
      and easy removal of drugs in cases of fetal or maternal anomalies, easy
      accetability for patients, but high cost.

PMID- 14581864
TI  - [Aerodiol: the efficacy and tolerability of intranasal estrogen administration.
      An overview].
AB  - Estrogen supplementation, given mainly by oral or transdermal route has been
      shown to decrease climacteric symptoms, bone turnover, prevent postmenopausal
      bone loss, and significantly reduce fracture risk in both early and late
      postmenopausal women. Estrogens exert their principal biological effects through
      the actions on 2 different intracellular estrogen receptor (ER) proteins, ERa and
      ERb. These receptors, are completely distinct in their action. However,
      regardless the type of receptor involved, the response induced through the action
      of ER induction can be dependent also on the total dose exposure rather than
      estradiol concentrations at subsaturating levels. The nasal route is an effective
      and well-established route of drug delivery. Nasal administration produces a
      pulsed profile of plasma estradiol, with plasma levels rising rapidly and
      returning to pre-administration levels within 12 h (fall to 10% of their peak
      level within approximately 2 h). As a consequence, daily intranasal
      administration results in a pulse-like estrogen profile, rather than the
      relatively sustained serum levels attained with both oral and transdermal
      administration. In addition, exposure obtained with a single dose is compared
      with the exposure obtained with the same total dose given as 2 divided doses
      administered 12 h apart. It's known that different route of administration exert
      different biological and clinical RESULTS: In the years, several clinical studies
      have demonstrated the efficacy and safety of intranasal estradiol in the
      treatment of climacteric symptoms, compared with other routes of estrogen
      administration. Interestingly, intranasal therapy also showed a lower tendency to
      stimulate endometrial proliferation than the oral route, with a high incidence of
      atrophic endometrium maintained during the long-term study. The reduced level of
      stimulation of the reproductive organs produced by Aerodiol compared with oral
      estradiol therapy of equivalent efficacy on climacteric symptoms may be related
      to the pulsed kinetic profile of estradiol exposure that occurs with the
      intranasal route. Improvement of climacteric symptoms observed with nasal
      estradiol administration is comparable to that seen with transdermal or oral
      estrogens. A similar reduction in Kupperman Index or in the number of hot flushes
      was reported over a 6-month period with results similar to those of several
      studies performed with transdermal patches delivering estradiol or with
      conjugated equine estrogen. Different routes of administration may exert
      different results in terms of compliance, biological and clinical effects even if
      long term clinical trials are needed for demonstrating it. The pulsed kinetics of
      Aerodiol may exert less side effects in terms of coagulation cascade activation
      and a favourable lipid profile with less mammary tissue stimulation. These
      aspects became of paramount importance since the recent publication of 2 trials,
      Women Health Initiative (WHI) and Heart and Estrogen/Progestin Replacement Study
      (HERS), regardless their important population selection bias and uncertain
      results, left important consequences in terms of HRT indication and use for both
      women and clinicians. In conclusion, Aerodiol introduces the new concept of
      pulsed estrogen therapy. Pulsed estrogen therapy is safe, well accepted and
      highly efficient in alleviating postmenopausal symptoms and prevent
      postmenopausal bone loss. Aerodiol therapy demonstrated also a lower stimulation
      of reproductive tissues (endometrium, breast) compared with the equivalent oral
      therapy, with important repercussion for future HRT strategies.

PMID- 14581865
TI  - Low dose hormone replacement therapy: clinical efficacy.
AB  - The frequency of hormone replacement therapy (HRT) users has increased during the
      last 2 decades. A majority of women taking HRT prefer to use formulations that
      will not induce bleeding disturbances. Accordingly many women prefer continuous
      combined HRT to obtain amenorrhoea. Previously comparatively high doses of
      estrogens and progestogens were prescribed to women in the climacteric period.
      Low doses of estrogens such as estradiol 1 mg and conjugated equine estrogens 0.3
      mg orally per day or transdermally applied estradiol 25 mug per 24 hours have
      been shown to be effective for the treatment of vasomotor symptoms and for
      prevention of bone loss. With low dose HRT in a continuous combined regimen
      amenorrhoea will be obtained in a majority of women after a few months of
      treatment. Low doses of progestogen especially if given on a continuous basis
      have been shown to protect the endometrium from hyperplasia. Favourable effects
      in lipid- and lipoprotein patterns have been reported. In addition, fewer side
      effects such as mastalgia have been found during treatment with low dose regimen
      compared to high doses. For women requesting HRT it might be a rational
      alternative to begin with low dose formulations since these doses are sufficient
      for the majority of women.

PMID- 14581866
TI  - Statin therapy in the heart and estrogen/progestin replacement study.
AB  - AIM: Limited data exists to guide secondary prevention in postmenopausal women
      with coronary heart disease (CHD). Treatment with HMG-CoA reductase inhibitors
      (statins) is likely to be beneficial for these patients. Yet, clinical trial
      results are conflicting. Moreover, significant interactions may exist between
      statins and hormone replacement therapy (HRT) that may complicate this approach.
      METHODS: In a post hoc analysis of the HERS trial, patients who were taking a
      statin were compared to those who were not. Subjects were randomized to HRT or
      placebo. Statin therapy was not controlled by the trial investigators, but may
      have been prescribed by the patients' primary physicians. Use of statins was
      monitored throughout the trial. The primary outcome was the composite of
      myocardial infarction and death resulting from CHD, with all-cause mortality and
      venous thromboembolism (VTE) as secondary outcome measures. RESULTS: At baseline,
      1004 subjects were taking a statin, with 1234 subjects randomized to receive HRT,
      and 1237 to receive placebo. Baseline statin use was associated with lower rates
      of the primary outcome (MI or fatal CHD, RH=0.78, 95% CI 0.61 to 0.99, p=0.044),
      and all-cause mortality (RH=0.74, 95% CI 0.56 to 0.99, p=0.04). Statin therapy
      was associated with a reduced incidence of VTE in both the HRT group and the
      placebo arm. The negative effect of HRT on the primary outcome seen in the 1st
      year of treatment was much reduced among baseline statin users and was no longer
      statistically significant (RH=1.34, 95% CI 0.63 to 2.86, p=0.45). CONCLUSION:
      Data from HERS supports the use of statins for secondary prevention in
      postmenopausal women with a history of cardiovascular disease. Statins may
      attenuate the increased cardiovascular risk of hormone replacement therapy.

PMID- 14581867
TI  - [Hormonal replacement therapy in menopause and cancer risk. An update].
AB  - The risk of breast cancer rises by about 2.3% per year of using estrogens and the
      risk is even higher in the case of combined therapy with estrogens and
      progestins; however the excess risk disappears 5 years after suspension of the
      treatment. The risk of endometrial tumour cancer is strongly associated with the
      use of estrogens but this increase is reduced or eliminated by the administration
      of progestinics for at least 12/14 days per month. The use of HRTs also seems to
      be directly associated with the risk of ovarian cancers, while they seem to exert
      a protective effect on colorectal neoplasms. The HRTs has favourable effects on
      bone metabolims, but they increase the risk of deep venous thrombosis and
      pulmonary embolism.

PMID- 14581868
TI  - [Depression, menopause and hormonal replacement therapy (HRT)].
AB  - The ovarian failure and the termination of reproductive female functions could
      influence the mental neurotransmission and the cognitive activity of menopausal
      women; female menopausal brain, one of the favorite estrogens target, could
      suffer of a negative homeostasis modification, affecting the daily behavior. So,
      neurotransmissive degeneration could expose aged women to some psychological
      disturbances, some of these frequently associated to hypoestrogenic hot flushes
      rise. Many studies showed the estrogen influence on female brain, and tried to
      explain how the hormonal replacement therapy (HRT), act on mood, life energy and
      cognitive activities. Although brain estrogenic activity seems to establish a
      useful role on neuromodulation and on the prevention of some psychopathologies,
      the conventional administration of HRT, improves the mood and menopausal female
      well-being, but it does not act on clinically depressed women.

PMID- 14581869
TI  - DNA fragmentation in human spermatozoa: significance in the diagnosis and
      treatment of infertility.
AB  - The integrity of the paternal genome is of paramount importance in the initiation
      and maintenance of a pregnancy in vivo and in vitro. The presence in the
      embryonic genome of chemical modifications at the level of DNA nucleotides and/or
      DNA strand breaks coming from the paternal genome (that have not been repaired by
      the oocyte after fertilization), is not compatible with normal embryo and fetal
      development. DNA fragmentation in human spermatozoa has been recently shown to be
      an important contributing factor to the etiology of unexplained infertility. In
      this review, the mechanisms responsible for DNA fragmentation in sperm, including
      defects in chromatin remodeling during the process of spermiogenesis, apoptosis
      and ROS-induced damage during sperm migration from the seminiferous tubules to
      the epididymis, are discussed. Also, the different methodologies used to
      determine DNA fragmentation in human sperm (with special emphasis on the SCSA
      test) and the applications of the SCSA test in the diagnosis and treatment of
      infertility, are presented. Finally, answers to common questions asked about the
      SCSA test are also included.

PMID- 14581870
TI  - [Dysfunctional uterine bleeding: medical therapies].
AB  - About a third of all gynecological consultations are carried out for abnormal
      uterine bleeding and this ratio rises to 70% in women in peri- and postmenopause.
      The diagnosis of dysfunctional uterine bleeding (DUB) which is generally due to a
      chronic anovulatory condition, is only arrived at after objective examination has
      excluded transvaginal echography, sonohysterography, hysteroscopy and if
      necessary biopsy to check for the presence of organic pathology. The drugs
      commonly used in DUB are methylergometrine, the antifibrinolytics, the FANS,
      estrogens, progesterone and its derivaties, the estroprogestinics, danazol and
      the superagonist analogues of GnRH. Following these simple guidelines, all
      derived from evidence-based medicine, medical treatments for DUB are certainly
      together with patient satisfaction but there is also a marked reduction in costs
      linked above all to the diminution in the number of hysterectomy operations.

PMID- 14581871
TI  - [Prenatal diagnosis of congenital diaphragmatic hernia: an update].
AB  - Congenital diaphragmatic hernia (CDH) has an incidence of approximately 1:4000
      live births. Most frequently the diaphragmatic defect is a left and
      posterolateral (Bochdalek) one. Prenatal diagnosis is made at ultrasonography;
      the relevant sonographic features will be described in the paper. Cystic
      adenomatoid malformation of the lung (CAML), pulmonary sequestration,
      bronchogenic cysts, pulmonary hypoplasia/agenesia need to be considered in
      differential diagnosis. In some cases, diagnosis of CDH is not possible "in
      utero": in such cases, herniation of abdominal viscera into the thorax takes
      place presumably just at delivery through a small diaphragmatic defect. CDH may
      be associated with intrauterine growth retardation (IUGR), chromosomal
      abnormalities (3%) and/or other malformations (10-50%): such as Central Nervous
      System, digestive, cardiac and urogenital anomalies. Therefore, search of
      associated malformations and amniocentesis with analysis of fetal karyotype are
      mandatory, whenever a CDH is diagnosed. CDH is still at present characterised by
      a high mortality (reportedly, about 45%). Many prognostic factors have been
      correlated to postnatal outcome of CDH: some of them are valuable prenatally by
      ultrasonography. However, the role of sonography in the prediction of neonatal
      outcome is still controversial: in particular, although many ultrasonographic
      parameters have been proposed, prenatal evaluation of pulmonary hypoplasia (a
      crucial factor related to postnatal survival) has not proved to be very accurate
      so far. Nevertheless, it is undisputable that prenatal diagnosis itself
      represents a crucial prognostic factor for CDH, since it allows birth of the
      affected fetuses in 3d level Perinatologic Centres provided with a Neonatal
      Intensive Care Unit and Neonatal Surgery.

PMID- 14581872
TI  - Sentinel Lymph Node (SLN) laparoscopic assessment early stage in endometrial
      cancer.
AB  - BACKGROUND: The aim of the study was to demonstrate the validity of sentinel
      lymph node (SLN) detection after injection of radioactive isotope and patent blue
      dye in patients affected by early stage endometrial cancer. The second purpose
      was to compare radioactive isotope and patent blue dye migration. METHODS:
      Between September 2000 and May 2001, 11 patients with endometrial cancer FIGO
      stage Ib (n=10) and IIa (n=1) underwent laparoscopic SLN detection during
      laparoscopic assisted vaginal hysterectomy with bilateral salpingo-oophorectomy
      and pelvic bilateral systematic lymphadenectomy. Radioactive isotope injection
      was performed 24 ours before surgery and blue dye injection was performed just
      before surgery in the cervix at 3, 6, 9 and 12 hours. A 350 mm laparoscopic gamma
      scintiprobe MR 100 type 11, (99m)Tc setted (Pol.Hi.Tech.), was used
      intraoperatively for detecting SLN. RESULTS: Seventeen SLN were detected at
      lymphoscintigraphy (6 bilateral and 5 monolateral). At laparoscopic surgery the
      same locations were found belonging at internal iliac lymph nodes (the so called
      "Leveuf-Godard" area, lateral to the inferior vescical artery, ventral to the
      origin of uterine artery and medial or caudal to the external iliac vein).
      Fourteen SLN were negative at histological analysis and only 3 positive for
      micrometastasis (mean SLN sections = 60. All the other pelvic lymph nodes were
      negative at histological analysis. The same SLN locations detected with g
      scintiprobe were observed during laparoscopy after patent blue dye injection.
      CONCLUSIONS: If the sensitivity of the assessment of SLN is confirmed to be 100%,
      this laparoscopic approach could change the management of early stage endometrial
      cancer. The clinical validity of this technique must be evaluated prospectively.

PMID- 14581873
TI  - [Epidural analgesia during labour: maternal, fetal and neonatal aspects].
AB  - AIM: The most effective technique for eliminating labour and childbirth pain is
      continuous lumbar epidural analgesia. The preoccupation regarding the possible
      negative effects on the time taken for labour and on dystocias in general
      represents one of the greatest hindrances in the way of its wider use. The
      purpose of the present study is to monitor the effects of continuous lumbar
      epidural analgesia on delivery times, on the state of the fetus, on the incidence
      of dystocic deliveries and on neonatal outcome. METHODS: Comparative prospective
      study. The data relating to the deliveries of 148 nulliparas and 51 pluriparas at
      term, submitted to epidural analgesia at the Obstetric Clinic of the University
      of Parma in 1999-2000 were compared with data from 144 nulliparas in labour and
      60 pluriparas without epidural analgesia, selected in random fashion out of 4251
      women who delivered children in the same period. The anesthetic procedure
      employed consisted in an injection of 20 mg/10 ml ropivacaine and 50 mg fentanyl
      in the epidural space at intervals of 1-2 h. RESULTS: The duration of the
      dilatation period was not influenced by administration of epidural analgesia
      while the expulsion period was longer in the course of epidural analgesia. There
      were no significant differences between delivery modalities in the 2 groups
      either as regards vaginal operative delivery or the number of cesarean sections
      for dystocia. The cardiotocographic profile was similar in the 2 groups. The
      neonatal outcome (Apgar index at 1' and 5' and transfer to the intensive care
      department) did not show significant differences, confirming the absence of
      noteworthy side-effects even from the neonatal standpoint. CONCLUSIONS: The use
      of low concentrations of ropivacaine (0.2%) associated with fentanyl in the
      epidural space proved to be a safe and effective technique for controlling labour
      and delivery pain.

PMID- 14581874
TI  - [Severe form of herpes gestationis].
AB  - We report a very severe form of herpers gestationis that arose at the 26(th) week
      of pregnancy and reached us for observation at the 30(th) week. Herpes
      gestationis in an autoimmune vesicobullous dermatosis characterised by skin
      eruptions, intense itching and consequent increase in fetal morbility, with
      delayed intrauterine growth and prematurity. Owing to its particular severity
      (involvement of the entire body surface including the face), between the 30th and
      the 32(nd) weeks we had to address a severe clinical condition characterised by
      anaemia, marked hypoproteinaemia, hypoalbuminaemia, hupertension and
      hyperglycaemia which led us to resort to the maximum dose of oral corticotherapy
      in association with topical therapy using clobetasol propionate. In our opinion
      the results obtained were highly statisfactory with the result that at the end of
      the 37(th) week, in consideration of the patient's obstetric history, podalic
      presentation and parity, we performed a Caesarean delivering a newborn of 3000 g
      in excellent condition. The patient was discharged symptom-free on the 6(th) day
      and the newborn was in full healt.

PMID- 14581875
TI  - [Laparoscopic conservative treatment of ovarian dermoid cysts].
AB  - Two methods for the laparoscopic dissection of dermoid ovarian cysts, less than
      10 cm, in 55 fertile women, are compared. Water dissection was performed in 23
      patients and bipolar scissors were used in 32 patients, creating a rhomb on the
      surface of the ovary, just to obtain a good traction for atraumatic dissection.
      The mean surgical time, complications and hospital stay have been compared.
      Operative laparoscopy is the technique of choice to remove most, if not all,
      ovarian dermoid cysts. It is suggested to use particular strategies in order to
      safely and easily dissect in toto the cysts.

PMID- 14581876
TI  - Adherence of Lactobacillus plantarum P 17630 in soft-gel capsule formulation
      versus Doderlein's bacillus in tablet formulation to vaginal epithelial cells.
AB  - BACKGROUND: To evaluate in vitro the adherence capability of two bacteria to
      vaginal epithelial cells (VEC) by comparing product A containing L. plantarum P
      17630, in soft-gel capsule formulation* and product B containing Doderlein's
      bacillus, now classified as L. gasseri, in vaginal tablet formulation, marketed
      for many years in Italy. METHODS: The comparative study of two commercially
      available preparations followed an open, controlled trial. Collection of VEC
      samples was done in an ambulatory setting; the adherence tests were carried out
      at the Institute of Microbiology of the Universita Cattolica del Sacro Cuore,
      Piacenza. The study was made on intact VEC, washed and drawn from 20 patients
      affected by bacterial vaginitis and/or vaginosis. One capsule or tablet,
      suspended in physiological solution, was mixed with a suspension of VEC.
      Adherence of lactobacilli to the VEC was counted by light microscopy and by CFU
      cultured on the plates. The type of adhesion was evaluated as well. RESULTS: The
      mean number of lactobacilli adhering to individual VEC was higher for product A
      containing L. plantarum P 17630. On the plate cultures, 10(6)-10(8) CFU/sample
      were found for product A, compared with 10(2)-10(4) CFU/sample for product B. L.
      plantarum P-17630 adhere prevalently to single cells, whereas L. gasseri adhere
      by forming small chains. CONCLUSIONS: Product A has a better capability of
      adherence to VEC than does product B. Even the type of adhesion of L. plantarum P
      17630 enabled it to remain better attached to the VEC. The results suggest that
      in vivo product A may be more likely to provide better colonization, thus
      affording better protection of the vaginal milieu.

PMID- 14581877
TI  - [Spontaneous rupture of the spleen in pregnancy].

PMID- 14581878
TI  - [Intrauterine grow restriction (IUGR). Importance of arginine administration].

PMID- 14581879
TI  - [Efficacy of methotrexate in the treatment of unruptured ectopic pregnancy].

PMID- 14581880
TI  - GnRH antagonist in in vitro fertilization: where we are now.
AB  - This review focuses on the recent literature concerning the use of GnRH
      antagonists in ovulation induction for in vitro fertilization (IVF). The GnRH
      antagonists, ganirelix acetate (Orgalutran/Antagon) and cetrorelix (Cetrotide),
      have come into increasingly common use since their release in the last 3 years.
      This class of GnRH analogue has several potential advantages over GnRH agonists.
      Among these advantages are: 1) shorter duration of injectable drug treatment, 2)
      decreased gonadotropin requirement per cycle, 3) improved patient convenience and
      4) lower overall treatment cost. As clinicians gain experience with these drugs,
      optimal treatment paradigms will likely emerge. This review will discuss current
      strategies and potential applications for the GnRH antagonists.

PMID- 14581881
TI  - The cryobiology of assisted reproduction.
AB  - Cryopreservation of human gametes and embryos has become an integral part of
      assisted reproduction. The major developments in cryopreservation technology have
      mirrored the rapid expansion of reproductive technology over the past 2 decades.
      It is now possible to cryopreserve sperm, oocytes and embryos at their various
      stages of development. The introduction of vitrification and rapid freezing
      techniques is gaining widespread recognition and may become the method of choice
      over traditional slow freezing methods. Ovarian tissue cryopreservation offers
      the hope of fertility preservation for women who are faced with potentially
      sterilizing medical or surgical treatments. Paralleling the introduction of
      cryobiology to assisted reproduction has been the realization of a number of
      moral and ethical issues related to gamete and/or embryo storage.

PMID- 14581882
TI  - Ovarian reserve, female age and the chance for successful pregnancy.
AB  - Both quantitative and qualitative factors regarding egg production are strong
      influences on IVF outcome. Markers of ovarian reserve such as basal FSH,
      clomiphene citrate challenge test (CCCT), and antral follicle counts are good
      predictors of the quantity of eggs which can be induced to grow. However, the
      quality of those eggs seems better predicted by the age of the women. In women
      past age 40, current success rates are low overall, even in those who good
      ovarian reserve who make many eggs; at this age, quantity does not make up for
      quality. By contrast, young women with limited ovarian reserve can have good
      success rates despite their limited cohort of eggs, because the eggs themselves
      are of high potential; here quality matters more than quantity. The ramifications
      of these observations include the following: diminished ovarian reserve should
      not be used as an exclusionary criterion in young women, because overall they
      still have satisfactory pregnancy rates, though their risk of cancellation is
      increased. In women past age 40, normal ovarian reserve testing is not reassuring
      because even reduced egg quality is likely to limit the opportunity for
      successful pregnancy no matter how many eggs are available.

PMID- 14581883
TI  - Endometriosis related to infertility.
AB  - Endometriosis is a disease affecting the physical health and emotional well being
      of many women worldwide. General estimates indicate that at least 25% of all
      women in their 30s and 40s may be suffering from endometriosis and 30-50% of the
      affected women are also infertile. Medical therapy, surgery and assisted
      reproduction are the 3 main options available to women affected by this
      condition. The etiology and pathophysiology of endometriosis-associated
      infertility are still obscure, despite an enormous effort over many decades. The
      management of this disease is a source of controversy and so far no consensus has
      been reached. Most studies show considerable variation in methodology, may not
      have enough statistical power or report results that are exactly the opposite of
      what has been previously published. In light of the disagreement that surrounds
      the study of endometriosis-associated infertility, a new comprehensive multi
      centre study should be designed with the international collaboration of all major
      experts in this field.

PMID- 14581884
TI  - Uterine fibroids: relationships to reproduction.
AB  - The purpose of this review is to summarize the available evidence on the effects
      of uterine fibroids on fertility, infertility and pregnancy outcomes, and the
      effects of parity on fibroids. Fibroids, found in approximately 4% of pregnant
      women, are associated with an increased risk of pregnancy complications. However,
      prophylactic myomectomy in asymptomatic women is not only unjustified, but it may
      have adverse effects on reproduction. Fibroids are found in 1% to 2.4% of women
      with unexplained infertility. Removal of fibroids that distort the uterine cavity
      may be beneficial in infertile women with unexplained infertility and in women
      undergoing in vitro fertilization. The pregnancy rate after hysteroscopic,
      laparoscopic or abdominal myomectomy appears to be the same. Laparoscopic
      myolysis appears to have adverse effects on pregnancy outcomes while uterine
      artery occlusion in infertile and fertile women requires urgent prospective
      evaluation. Parity appears to be a natural global killer of uterine fibroids,
      most likely, through transient uterine ischemia, similar to that of uterine
      artery occlusion.

PMID- 14581885
TI  - Polycystic ovary syndrome and ovulation induction.
AB  - Polycystic ovary syndrome (PCOS) is likely the most common cause of anovulatory
      infertility. Although many options are available for ovulation induction in these
      patients, there is currently no evidence-based algorithm to guide the initial and
      subsequent choices of ovulation induction methods. In obese women with PCOS, mild
      to moderate weight loss results in improvement of ovulatory dysfunction, and
      should be advocated at the onset of the evaluation. Clomiphene citrate is
      currently the 1st line medical therapy for ovulation induction. Glucocorticoids
      do not result in consistent ovulation and have significant side effects.
      Exogenous pulsatile GnRH treatment has low ovulation and pregnancy rates with a
      high risk of miscarriage. The most commonly used medical agents for ovulation
      induction in clomiphene-resistant women with PCOS are parenteral gonadotropins.
      Various gonadotropin preparations and different protocols are available; however
      the risk of multiple pregnancy and ovarian hyperstimulation is high with
      gonadotropin therapy. The frequent association between PCOS and insulin
      resistance has prompted recent studies on the effect of insulin-sensitizing
      agents on spontaneous and as an adjuvant to conventional ovulation induction
      therapies. Overall, the improvement in ovulation with insulin sensitizing drugs
      is modest, and unresolved issues such as variability in ovarian response remain
      to be addressed in future studies. Nevertheless, these agents may be beneficial
      in a subset of PCOS patients. Surgical ovulation induction methods such as
      ovarian diathermy have been reported to be moderately effective. However, due to
      the inherent associated risks and unknown effect on long-term reproductive
      potential, this modality should be reserved for patients who are clomiphene
      resistant and unable or unwilling to proceed to gonadotropin therapy.

PMID- 14581887
TI  - Environmental toxicants and human fertility.
AB  - Globally there is increasing concern that the environment is having a negative
      impact on human health. Hormone-like activity and endocrine toxicity of
      environmental toxicants have been documented in the contemporary literature
      raising concern that exposure to these chemicals could alter human reproductive
      function and affect fertility. In addition, epidemiological reports of an
      association between exposure to chemical toxicants in the workplace and adverse
      reproductive outcomes together with detection of environmental toxicant residues
      in serum and ovarian follicular fluid, has led to widespread concern that
      chemical contaminants may be a contributing factor in the pathobiology of
      idiopathic infertility in the general population. While the epidemiological
      evidence is equivocal, animal studies provide biological plausibility for a
      potential association between environmental toxicant exposures and altered
      reproductive function. Furthermore, cell and organ culture experiments illustrate
      potential mechanisms of toxicant action on the reproductive system. This review
      summarizes the evidence linking environmental toxicant exposure and infertility
      and examines the biological plausibility for this association.

PMID- 14581886
TI  - Recurrent spontaneous early pregnancy loss and low dose aspirin.
AB  - Miscarriage is the most common complication of pregnancy, occurring in 10-15% of
      pregnant women. Accurate figures on prevalence are not available but it has been
      estimated that 2-5% of women have 3 or more miscarriages. The lack of
      methodological rigour in controlled trials of treatment efficacy in women with
      recurrent miscarriage makes it difficult to estimate the efficacy of treatment
      for this condition. To date, there is no evidence of improved outcome with
      aspirin compared to placebo or no treatment. Furthermore, animal data and limited
      human data suggest that prenatal use of aspirin may be associated with increased
      bleeding tendency, congenital malformations and cognitive and behavioural defects
      in the offspring. Seen and considered the lack of efficacy of low-dose aspirin
      and the potential for harm to the female and her offspring, the practice of
      recommending aspirin to women with recurrent miscarriage should be discontinued.

PMID- 14581888
TI  - Problems with dogmatic ethicism in infertility treatment.

PMID- 14581889
TI  - Multiple myeloma: increasing our treatment options.

PMID- 14581890
TI  - Bortezomib (PS-341): a novel, first-in-class proteasome inhibitor for the
      treatment of multiple myeloma and other cancers.
AB  - BACKGROUND: Multiple myeloma (MM) is an incurable malignancy that is diagnosed in
      approximately 15,000 people in the United States each year. The novel proteasome
      inhibitor bortezomib has shown antitumor activity in preclinical studies and has
      entered clinical trials, with encouraging results to date. METHODS: We review and
      summarize preclinical work demonstrating the tumoricidal effects of proteasome
      inhibition, focusing on the potent and selective proteasome inhibitor bortezomib,
      the first such agent to progress to clinical trials. We also address the
      potential for bortezomib as a therapy for MM. RESULTS: In preclinical studies
      bortezomib appears not only to have activity against MM cells, but also to
      downregulate protective interactions with bone marrow stromal cells and to
      inhibit blood vessel development. Proteasome inhibition also has been shown to
      interfere with protective interactions between MM cells and the bone marrow, and
      to restrict tumor-associated angiogenesis in preclinical models. CONCLUSIONS:
      Proteasome inhibition is a promising new investigational avenue for cancer
      therapy. Bortezomib is currently available for the treatment of relapsed and
      refractory MM. Further trials are underway to assess the safety and efficacy of
      this agent in MM and a range of other cancers.

PMID- 14581891
TI  - Trials of arsenic trioxide in multiple myeloma.
AB  - BACKGROUND: Several reports on the use of arsenic trioxide (ATO), mainly in acute
      promyelocytic leukemia, have led to a renewed interest in ATO in the management
      of malignancies, especially those of hematologic origin such as multiple myeloma
      (MM). MM remains an incurable disease, with median survival rates of 4-6 years.
      Thus, newer treatments with good safety profiles are needed to improve the
      quality of responses, prolong progression, and increase overall survival. METHOD:
      The current state of the art regarding the role of ATO in the management of MM
      and the rationale for this consideration is reviewed. RESULTS: Preclinical
      evidence suggests that one of the mechanisms in which ATO exerts its antimyeloma
      effect is by immunologic mechanisms. One such mechanism appears to be achieved by
      a marked increase in lymphokine-activated killer (LAK)-mediated killing and up
      modulation of CD38 and CD54, two molecules involved in cell-cell interactions.
      Two phase II trials have shown that the drug appears to be clinically effective.
      CONCLUSIONS: With the improved understanding of the interaction between the
      myeloma cell and its microenvironment as well as the cytokine support system, it
      does not appear than any particular agent will be able to control the disease
      permanently. In the clinical arena, the next generation of studies will be
      designed to combine different molecules to take advantage of non-overlapping
      toxicities and to compromise the extensive and redundant myeloma support system,
      thus controlling the disease in a chronic phase.

PMID- 14581892
TI  - Thalidomide and its derivatives: new promise for multiple myeloma.
AB  - BACKGROUND: The combination of melphalan and prednisone has been accepted as
      standard treatment for multiple myeloma (MM) because most studies demonstrate
      only minimal survival benefit of combination chemotherapy regimens when compared
      with melphalan and prednisone. Despite modest gains with more intensive
      myeloablative regimens for certain subgroups, myeloma remains incurable. In 1999,
      investigators at the University of Arkansas reported the promising results of a
      phase II study of thalidomide in patients with resistant MM. Since then various
      trials of thalidomide alone, and in combination, have been tested in patients
      with resistant, and more recently, untreated MM. In addition, preliminary results
      of phase I studies of the immunomodulatory derivatives (IMiDs) of thalidomide
      have recently been reported. METHODS: The author reviewed and reports the results
      of clinical trials of thalidomide and the IMiDs, as well as the pharmacology,
      mechanism of action, and toxicity of these agents. RESULTS: Thalidomide has
      demonstrated significant activity in both resistant and previously untreated
      multiple myeloma. Combination therapy with dexamethasone increases response rate,
      even in patients previously resistant to both drugs given as single agents,
      indicating probable synergy. More recent studies of thalidomide-dexamethasone in
      previously untreated patients are encouraging. IMiD-3 is active in resistant
      myeloma and has a toxicity profile different from that of thalidomide.
      CONCLUSIONS: Many studies have confirmed the activity of thalidomide in MM, as
      well as more responses with dexamethasone. Newer thalidomide derivatives with
      reduced toxicity are promising. Thalidomide-dexamethasone may now represent the
      treatment of choice for previously untreated patients. Further studies with these
      and other novel agents early in the course of myeloma, followed by rational
      programs of dose intensification, may improve complete remission rates and the
      frequency of long-term control.

PMID- 14581893
TI  - Farnesyltransferase inhibitors and their role in the treatment of multiple
      myeloma.
AB  - BACKGROUND: Ras mutations are among the most common oncogene mutations found in
      multiple myeloma (MM). Patients with mutated Ras are less likely to respond to
      chemotherapy and have a shortened median survival. Therefore, targeting Ras
      farnesylation may be a valuable approach to treatment of MM. R115777 (tipifarnib)
      is a potent farnesyltransferase inhibitor (FTI) presently undergoing phase II/III
      clinical trials. METHODS: We reviewed the preclinical and clinical experience of
      FTIs as antineoplastic agents and describe their potential role in the treatment
      of MM. RESULTS: FTIs are a novel group of agents that selectively inhibit
      farnesyltransferase, an enzyme responsible for the posttranslational modification
      of several proteins including Ras. Since Ras is among the most commonly mutated
      oncogenes associated with cancer, this class of drugs has been evaluated in
      clinical trials in a diversity of tumors. R115777 has been evaluated in a phase
      II clinical trial in patients with advanced myeloma and found to be well
      tolerated. It induced disease stabilization in more than 60% of patients with
      advanced myeloma. CONCLUSIONS: The drug selectively targets farnesyltransferase,
      but this effect did not correlate with disease stabilization, suggesting that
      these drugs may be targeting a survival pathway independent of Ras processing.
      Further studies will evaluate the use of FTI in maintenance therapy as well as in
      combination with other agents in advanced myeloma.

PMID- 14581894
TI  - Gefitinib (ZD1839) in previously treated advanced non-small-cell lung cancer:
      experience from a single institution.
AB  - BACKGROUND: We conducted an analysis of gefitinib in patients with advanced non
      small-cell lung cancer (NSCLC) to assess the antitumor efficacy of this epidermal
      growth factor receptor tyrosine kinase inhibitor. METHODS: Our single-center,
      prospective landmark analysis included 183 patients with advanced NSCLC who
      received 250 mg of gefitinib orally once daily in an expanded-use program at our
      institution. Thirty-three of the 183 patients were previously untreated. The
      patients included in this analysis had all received at least 12 weeks of
      gefitinib. RESULTS: The objective tumor response rate was 3.8%, but an additional
      53.5% of patients experienced clinically meaningful disease stabilization. Median
      progression-free survival time was 3.6 months, and median overall survival time
      was 8.8 months. The 1-year survival rate for the entire cohort was 35%.
      Predictors of longer survival included female gender, adenocarcinoma or
      bronchoalveolar carcinoma histology, and an Eastern Cooperative Oncology Group
      performance status of 0 or 1. Adverse events were generally mild (grade 1 or 2)
      and consisted mainly of skin reactions and diarrhea. CONCLUSIONS: In this single
      center experience, gefitinib demonstrated clinically significant antitumor
      activity and provided good palliation in a predominantly pretreated group of
      patients. Our results, which are likely to be reproducible in a community
      setting, demonstrated a 1-year survival rate of 35% in a cohort of patients who
      were able to take the drug for at least 12 weeks.

PMID- 14581895
TI  - Factors associated with early termination of CHOP therapy and the impact on
      survival among patients with chemosensitive intermediate-grade non-Hodgkin's
      lymphoma.
AB  - BACKGROUND: Six to eight cycles of CHOP therapy (cyclophosphamide, doxorubicin,
      vincristine, and prednisone) is standard for intermediate-grade non-Hodgkin's
      lymphoma (NHL) but is associated with toxicity that may cause premature
      termination of therapy. METHODS: We studied factors associated with premature
      termination of CHOP therapy (receiving fewer than 6 cycles) and the relationship
      of premature termination with survival. Subjects consisted of a population-based
      sample of Iowa residents with intermediate-grade NHL who were planned to receive
      > or = 6 or more cycles of CHOP and who were chemosensitive (ie, achieved a
      documented partial or complete response to CHOP). RESULTS: In a comparison with
      patients 18-59 years of age, the odds of premature termination of CHOP therapy
      was 2.6 (95% CI, 0.7-9.2) for those aged 60-74 and 6.2 (95% CI, 1.7-23.3) for
      those aged > or = 75. Patients with cycle 1 febrile neutropenia hospitalization
      (FNH) were 4.4 times (95% CI, 1.4-13.8) more likely to terminate CHOP prematurely
      than those without cycle 1 FNH. Among patients aged 60-74, but not those aged >
      or = 75, premature termination appeared to be associated with decreased 5-year
      survival (hazard ratio [HR] = 6.0; 95% CI, 2.4-15.2) compared with those
      completing CHOP therapy (HR = 2.1; 95% CI, 1.0-4.2). Findings for overall
      survival were similar. CONCLUSIONS: First-cycle FNH and age > or = 60 years were
      associated with premature termination of CHOP therapy. The association of
      premature termination with survival among chemosensitive patients differed by
      age.

PMID- 14581896
TI  - A case report of invasive ductal adenocarcinoma identified in a lymphatic
      channel: a staging controversy.

PMID- 14581898
TI  - Cancer care for diverse populations: relevant communications and research.

PMID- 14581897
TI  - Successful voriconazole therapy of disseminated Fusarium solani in the brain of a
      neutropenic cancer patient.

PMID- 14581899
TI  - Training community practitioners in a research intervention: practice examples at
      the intersection of cancer, Western science, and native Hawaiian healing.
AB  - This practice paper describes the preintervention training component of a
      feasibility study exploring the use of ho'oponopono, an indigenous Hawaiian
      healing practice, for enhancing psychosocial adaptation to breast cancer among
      Native Hawaiian women. Practitioners' adherence to research protocols and
      competence in intervention delivery are both regarded as essential to obtaining
      valid results in tests of intervention feasibility and efficacy; thus, training
      in this study dually focused on fortification of adherence and enhancing
      competence among those recruited to deliver the ho'oponopono intervention. A
      manual-based training, using adult pedagogical strategies infused with Native
      Hawaiian cultural practices, was delivered to community practitioners. Effects of
      the training on practitioners' knowledge and skills were evaluated through
      multiple methods. Knowledge significantly increased between pre- and post
      intervention assessment. However, knowledge application for some practitioners
      was hindered by skill deficits, stylistic differences, and cultural conflict.
      Ongoing attention to competence and adherence is indicated. In-service training
      may bolster competence; however, practitioners may have difficulty in adhering to
      protocols for different reasons, and individualized clinical supervision and
      cultural consultation may be helpful in some situations.

PMID- 14581900
TI  - Replication and dissemination of a cancer education model for African American
      women.
AB  - The purpose of this study was to investigate the effectiveness of replicating an
      evidence-based model, the Witness Project, for increasing breast and cervical
      cancer screening with African American women in a variety of locations and
      organizations in the United States. The quantitative and qualitative methods
      included a cadre of process and outcome measures to evaluate the effectiveness of
      the four-phase replication process. The intervention was replicated in 25 sites
      with 401 volunteers, delivering cancer education and screening programs to over
      10,000 women. Key components and criteria of successful replication were
      established, and preliminary screening outcomes demonstrated a 43.4% increase in
      mammography in women aged 40 and older. This study demonstrates that the Witness
      Project model can be effectively replicated, that the replication process can be
      standardized, and that the replication sites were able to obtain positive
      screening results comparable to the original intervention outcomes. The model was
      not able to be effectively replicated with just the "turnkey" toolbox approach,
      but required additional technical assistance.

PMID- 14581901
TI  - Assessing cancer beliefs in a Chinese immigrant community.
AB  - Although many studies have focused on cancer screening utilization and attitudes,
      no study has yet been conducted that examines community beliefs toward a cancer
      diagnosis and some of the beliefs about cancer and cancer patients. While certain
      types of cancer have been decreasing in the White population, minority
      populations are more likely to be diagnosed in a later stage and die of cancer.
      Stigmas caused by a cancer diagnosis and the disease itself may be a contributing
      factor in late detection and increased mortality. A telephone survey of 798
      Chinese immigrants living in San Francisco was conducted. Subjects were asked
      several questions with established responses regarding their beliefs about
      cancer. One quarter of the 798 participants still believe cancer is contagious.
      Many also believe cancer is caused by environmental as well as personal action
      such as immoral behavior. A logistic regression model indicated that women who
      are at a low income level and have resided in the United States for an extended
      period of time are more likely to believe cancer is contagious. Community stigmas
      toward cancer and cancer survivors will prevent some Chinese immigrants from
      seeking early diagnosis. Multimedia education efforts that utilize print,
      television, and radio may provide a point of entry to reach otherwise unreachable
      individuals. This concerted education effort may help to dispel some of the myths
      regarding cancer, its treatment, and prognosis. It is hoped this would encourage
      a healthy dialogue about cancer, thus increasing screening and early detection
      among Chinese immigrants.

PMID- 14581902
TI  - Lessons learned while developing "Clinical Trials Education for Native Americans"
      curriculum.
AB  - This paper highlights lessons learned while developing the Clinical Trials
      Education for Native Americans (CTENA) curriculum. The CTENA is a culturally
      specific clinical trials education curriculum that evolved from another ongoing
      NCI-supported project, Clinical Trials Education for Colorado Providers. The
      multicultural team learned many lessons while developing, pretesting, and
      revising this curriculum. These include allocating sufficient time and resources
      to tailor presentations for diverse tribal settings and workshop participants,
      addressing barriers to participation in clinical trials through culturally
      appropriate strategies, providing information to foster informed decision making
      related to participation, and writing as a team to increase cultural breadth of
      examples and interactive experiences. There are multiple challenges to developing
      and implementing a culturally acceptable curriculum on clinical trials within
      medically underserved communities. Both the multicultural team and the curriculum
      benefited from the collaborative process, resulting in a culturally relevant
      clinical trials curriculum that will assist Native Americans to make informed
      choices about clinical trials participation. The lessons shared here, which may
      need to be modified to be culturally relevant to other underrepresented
      communities, may be beneficial to others developing similar curricula for other
      medically underserved populations.

PMID- 14581903
TI  - Development of a spiritually based breast cancer educational booklet for African
      American women.
AB  - Breast cancer is a significant health problem among African American women. Since
      the church is a viable health education venue for this population, spiritual
      cancer communication is a timely area of study to promote cancer education. In
      partnership with an African American church, we developed an educational booklet
      on breast cancer early detection from within a spiritual framework. Working with
      an advisory panel of women from the church, we facilitated the development of the
      booklet content and design. Panel members selected the spiritual themes and
      scripture used to frame the early detection messages, and they wrote messages to
      be included in the booklet. Meetings with focus groups were conducted to generate
      feedback on the booklet design and content. Overall feedback from the advisory
      panel and three focus groups regarding this level 4 spiritually based cancer
      communication intervention for African American women was generally consistent,
      showing strong preferences for design and content. We believe that this
      spiritually based approach may be one way to make cancer communication more
      culturally appropriate for African American women.

PMID- 14581904
TI  - Internet use for cancer information among racial/ethnic populations and low
      literacy groups.
AB  - Many Web sites on the Internet offer health information related to cancer and are
      increasingly being used by patients, caregivers, and those interested in cancer
      prevention and treatment. To comprehensively review the cancer literature
      regarding Internet health information use among those of racial/ethnic
      populations and low literacy groups, a comprehensive review of the MEDLINE/Pre
      MEDLINE, LISA, PsycInfo, CINAHL, Embase, and Web of Science databases was
      conducted. Eight relevant articles were retrieved: seven are classified as
      content research and one as outcomes research. Little empirical research exists
      on this topic of cancer Internet health information use among those of
      racial/ethnic populations and low literacy groups. This area of research is open
      for many unique contributions to the scientific literature.

PMID- 14581905
TI  - Inner resources as predictors of psychological well-being in middle-income
      african american breast cancer survivors.
AB  - Although African American women are exposed to major life stressors such as
      breast cancer, many have high levels of psychological well-being (PWB). However,
      there are no current studies that describe the psychological effects of applying
      sense of coherence, hope, and spiritual perspective by African American breast
      cancer survivors. These three inner resources have each been positively
      associated with PWB or coping. This correlational study tested the Gibson Model
      of Inner Resources in 162 African American breast cancer survivors who completed
      the Abbreviated Herth Hope Index, Spiritual Perspective Scale, Sense of Coherence
      Scale (13-item) and the Quality of Life/Breast Cancer (PWB Subscale). Statistical
      analyses included correlation, multiple regression, and path analysis. Study
      findings supported the model. Sense of coherence significantly accounted for
      37.5% and hope for 5.3% of PWB. Spiritual perspective did not significantly
      account for any of the variance, but there was an indirect path from spiritual
      perspective through hope to PWB. Sense of coherence and hope were direct
      predictors; however, spiritual perspective and hope together were predictors of
      PWB. Health professionals should consider strategies to enhance sense of
      coherence and hope when caring for African American breast cancer survivors.
      Qualitative research is indicated to further explore spirituality in this
      population.

PMID- 14581906
TI  - Implications for breast and cervical cancer control for Latinas in the rural
      South: a review of the literature.
AB  - The Latino population has more than tripled in six southern US states. Little
      research exists describing the Latino population in the rural South and the
      unique cancer control needs of this group. This article reviews existing
      literature on Latinas with a focus on rural southern settlement processes and
      applicable breast and cervical cancer control research. Recommendations for
      effective cancer control programs include developing special outreach efforts
      conducted with monolingual Latinas, incorporating important cultural components
      and values related to family, spirituality, and community, and designing programs
      that incorporate low-literacy materials and messages or that do not require
      literacy to participate. Understanding the social, cultural, and economic issues
      that Latinas face is an important first step in designing culturally relevant
      breast and cervical cancer control.

PMID- 14581907
TI  - Sociocultural characteristics and responses to cancer education materials among
      African American women.
AB  - Culture has been linked to cancer-related beliefs and practices. The purpose of
      the present study was to examine the effects of culture on responses to cancer
      education materials. Religiosity, collectivism, racial pride, and time
      orientation were measured among 1,227 African American women. Analyses tested the
      hypothesis that women scoring higher and lower on each construct would differ in
      their liking, attention, attitude change, recall, and perceived relevance of
      tailored materials that did or did not frame cancer issues in a cultural context.
      Responses to culturally tailored materials were no different than responses to
      other materials, regardless of women's cultural characteristics. However, for all
      types of materials, women scoring high on religiosity or racial pride paid more
      attention to materials, liked them more, and found them more personally relevant
      than women low on these constructs (all ps<.005). Women scoring high on present
      time orientation paid less attention to materials than women low on this
      construct (P<.01). In this population of women, cultural characteristics appear
      to moderate responses to tailored health education materials.

PMID- 14581908
TI  - Combining cancer control information with adult literacy education: opportunities
      to reach adults with limited literacy skills.

PMID- 14581909
TI  - Decision-making issues for randomized clinical trial participation among
      Hispanics.

PMID- 14581910
TI  - Smoking cessation interventions among African Americans: research needs.

PMID- 14581912
TI  - Misdiagnosis of stroke in tissue plasminogen activator-treated patients:
      characteristics and outcomes.
AB  - STUDY OBJECTIVE: Misdiagnosis of acute ischemic stroke is a risk inherent in
      treating patients with acute deficits, yet few data exist on the problem. We
      report an evaluation of emergency department misdiagnoses in patients treated
      with tissue plasminogen activator for acute ischemic stroke. METHODS: We
      conducted an observational study of 151 consecutive patients treated without an
      acute stroke team. Initial diagnosis was compared with interim and hospital
      discharge diagnoses. Separate analyses were performed for patients without a
      final diagnosis of acute ischemic stroke and for those without a final diagnosis
      of either acute ischemic stroke or transient ischemic attack, combined. RESULTS:
      Ten of 151 patients (7%; 95% confidence interval [CI] 3% to 12%) had final
      diagnoses that did not include acute ischemic stroke. Six of 151 (4%; 95% CI 1%
      to 8%) had a final diagnosis other than acute ischemic stroke or transient
      ischemic attack (conversion disorder [4], complex migraine [1], and Todd's
      paralysis [1]). These "stroke mimics" had no intracranial hemorrhage (0%; 95% CI
      0% to 31%), had less disability at discharge (modified Rankin Scale score mean+/
      SD, 2.2+/-1.3 versus 3.2+/-1.8), and were younger (mean age+/-SD, 47+/-21 years
      versus 68+/-15 years) than patients with acute ischemic stroke or transient
      ischemic attack. An additional 4 (3%) patients had interim diagnoses other than
      acute ischemic stroke, all subsequently changed to acute ischemic stroke after
      magnetic resonance imaging or computed tomography. CONCLUSION: These data show
      that in a 4-hospital system without an acute stroke team, thrombolytic treatment
      of patients with diagnoses mimicking stroke was infrequent, and hemorrhagic
      complications did not occur in any patients without an acute ischemic stroke.
      However, because the number of mimics was small, safety cannot be ensured with
      statistical confidence.

PMID- 14581913
TI  - Association between course of blood pressure within the first 24 hours and
      functional recovery after acute ischemic stroke.
AB  - STUDY OBJECTIVE: The relation between course of blood pressure within the first
      24 hours after acute stroke and early neurologic outcome remains a matter of
      dispute. We investigate this relation with adjustment for other influencing
      variables. METHODS: Three hundred seventy-two patients with the diagnosis of
      ischemic stroke were included to evaluate the relation between blood pressure
      course and early neurologic outcome. The following data were collected: age; sex;
      history of hypertension, diabetes mellitus, hyperlipidemia, coronary heart
      disease, peripheral vascular disease, and stroke; smoking habits; preadmission
      blood pressure, blood pressure on admission, and blood pressure 24 hours later;
      antihypertensive treatment; and stroke localization. We assessed outcome at day 5
      after admission as dependent or independent (Rankin Scale score <or=2) and
      applied multivariate logistic regression analysis to investigate the effect of
      blood pressure changes on outcome, with adjustment for other baseline variables.
      RESULTS: Relative changes of systolic and diastolic blood pressure within
      hospital admission to 24 hours after admission revealed significant differences
      of patients' neurologic outcome only for diastolic blood pressure changes from
      admission to 24 hours. A diastolic blood pressure decrease more than 25% from
      admission until 24 hours after admission was associated with a 3.8-fold increased
      adjusted odds (95% confidence interval 1.2 to 12.1) for poor neurologic outcome
      on day 5 (Rankin Scale score 3 to 5). CONCLUSION: Excessive diastolic blood
      pressure reduction was associated with an increased risk for an impaired
      neurologic outcome in patients with ischemic stroke. The association between both
      characteristics was independent from concomitant risk factors, stroke
      localization, and possible antihypertensive treatment.

PMID- 14581914
TI  - When is a patient safe for discharge after procedural sedation? The timing of
      adverse effect events in 1367 pediatric procedural sedations.
AB  - STUDY OBJECTIVES: The optimal timing of discharge from the emergency department
      (ED) after pediatric procedural sedation and analgesia has not been well studied.
      Because concern about delayed adverse effects commonly delays discharge after
      sedation, we attempted to establish the timing of adverse effects in our cohort
      of procedural sedations. METHODS: We analyzed data from a prospectively generated
      database comprising consecutive sedation events throughout a 2-year period. We
      determined the timing of serious (eg, hypoxia, stridor, hypotension) and other
      adverse effects from final medication administration and calculated adverse
      effect risk ratios in relation to sedation characteristics. RESULTS: In 1341
      sedation events, there were 184 (13.7%) adverse effects, of which 159 (11.9%)
      were serious. The median age of children with and without adverse effects was
      similar (64 months in both groups). Most adverse effects occurred during the
      procedure (92%) rather than after the procedure (8%). Serious adverse effects
      occurred a median of 2 minutes after final medication dose (range -106 to +40
      minutes). One hypoxic episode occurred each at 26, 30, and 40 minutes after final
      medication administration; all were repeated occurrences in children who had
      experienced previous hypoxia during the expected peak drug effect. CONCLUSION:
      Adverse effects were common; however, serious adverse effects rarely occurred
      after 25 minutes from the final medication administration. Those that did occur
      this late were all preceded by a separate similar adverse effect during the
      expected peak drug effect, which suggests that when similar medication regimens
      are used, discharge from the ED may be safe at approximately 30 minutes after
      final sedation medication administration if no adverse effects have occurred.

PMID- 14581915
TI  - Preprocedural fasting state and adverse events in children undergoing procedural
      sedation and analgesia in a pediatric emergency department.
AB  - STUDY OBJECTIVE: Assessment of preprocedural fasting is considered essential in
      minimizing the risks of procedural sedation and analgesia. Established fasting
      guidelines are difficult to follow in the emergency department (ED). We
      characterize the fasting status of patients receiving procedural sedation and
      analgesia in a pediatric ED and assess the relationship between fasting status
      and adverse events. METHODS: A prospective case series was conducted in a
      children's hospital ED during an 11-month period. All consecutive patients
      requiring procedural sedation and analgesia were included. Preprocedural fasting
      state and adverse events were recorded. The percentage of patients undergoing
      procedural sedation and analgesia who did not meet fasting guidelines was
      determined. Adverse events were analyzed in relation to fasting status. RESULTS:
      One thousand fourteen patients underwent procedural sedation and analgesia, and
      data on fasting status were available for 905 (89%) patients. Of these 905
      patients, 509 (56%; 95% confidence interval [CI] 53% to 60%) did not meet fasting
      guidelines. Seventy-seven adverse events occurred in 68 (6.7%; 95% CI 5.2% to
      8.4%) of the 1,014 patients. All adverse events were minor and successfully
      treated. Adverse events occurred in 32 (8.1%; 95% CI 5.6% to 11.2%) of 396
      patients who met and 35 (6.9%; 95% CI 4.8% to 9.4%) of 509 patients who did not
      meet fasting guidelines. There was no significant difference in median fasting
      duration between patients with and without adverse events and between patients
      with and without emesis. Emesis occurred in 15 (1.5%) patients. There were no
      episodes of aspiration (1-sided 97.5% CI 0% to 0.4%). CONCLUSION: Fifty-six
      percent of children undergoing ED procedural sedation and analgesia were not
      fasted in accordance with established guidelines. There was no association
      between preprocedural fasting state and adverse events.

PMID- 14581916
TI  - Fasting is a consideration--not a necessity--for emergency department procedural
      sedation and analgesia.

PMID- 14581917
TI  - Nonoccupational postexposure HIV prevention: emergency physicians' current
      practices, attitudes, and beliefs.
AB  - STUDY OBJECTIVE: We surveyed emergency physicians to determine current practices,
      knowledge, attitudes, and beliefs regarding nonoccupational postexposure
      prevention practices. METHODS: Two thousand randomly selected practicing
      emergency physicians from the American College of Emergency Physicians' national
      database and all graduating emergency medicine residents in 2000 were surveyed.
      Knowledge, role responsibility, self-efficacy, and attitudes and beliefs were
      measured and composite scores developed. Differences in responses between
      supporters and nonsupporters were compared for each category. RESULTS: Eight
      hundred eighty-nine responded, representing 60% (67/113) of emergency medicine
      residencies, 32% (347/1095) of emergency medicine residents, and 27% (542/2000)
      of emergency physicians. Responders recommend nonoccupational postexposure
      prevention for sexual assault (35%), unintentional needle stick (25%), and,
      rarely (<15%), for unsafe sexual practices and injection drug use. Knowledge of
      Centers for Disease Control and Prevention recommendations or the time when
      treatment may be most beneficial is poor (15.5% and 13.7%, respectively). Most
      agree their role includes providing nonoccupational postexposure prevention drugs
      and referring patients for counseling (76.5% and 75.6%, respectively). Confidence
      in assessing need for nonoccupational postexposure prevention varied with
      exposure type (sexual assault [61.6%], unintentional needle stick [54.8%], unsafe
      sexual practices [40.4%], and injection drug use [49.7%]). Supporters of
      nonoccupational postexposure prevention (64.1%) are more likely to have
      nonoccupational postexposure prevention available (69.3% versus 42.9%; 95%
      confidence interval [CI] 19.7 to 33.1), written protocols (42.5% versus 33.0%;
      95% CI 2.8 to 16.2), and higher mean composite scores than nonsupporters in all
      categories: knowledge, self-efficacy, role responsibility, and attitudes.
      CONCLUSION: Most emergency physicians surveyed agree that offering
      nonoccupational postexposure prevention is feasible and within their role
      responsibility. Establishing nonoccupational postexposure prevention protocols
      and providing educational programs are important first steps in changing
      practice.

PMID- 14581919
TI  - Update on emerging infections: news from the Centers for Disease Control and
      prevention. Update: Multistate outbreak of monkeypox--Illinois, Indiana, Kansas,
      Missouri, Ohio, and Wisconsin, 2003.

PMID- 14581918
TI  - HIV postexposure prophylaxis in the emergency department: the morning after is
      today.

PMID- 14581920
TI  - Emergency medicine tools to manage smallpox (vaccinia) vaccination complications:
      clinical practice guideline and policies and procedures.
AB  - In December 2002, the federal government began a program to immunize
      approximately 500000 civilian public health and health care workers with smallpox
      (vaccinia) vaccine as a part of our pre-event defense against bioterrorism. First
      responders will likely follow, and the general US population might be offered
      vaccination in the next 1 to 2 years. Recent reports that suggest the possible
      association of the vaccine to adverse cardiac events (including deaths),
      liability concerns for hospitals, and the availability of compensation for
      workers with vaccine complications have significantly reduced voluntary
      participation. Vaccinees might experience robust primary takes or serious adverse
      events, including viral or even bacterial cellulitides, encephalitis, progressive
      skin destruction, and other life-threatening complications. With the increasing
      prevalence of immune suppression from both diseases and immunosuppressive
      medications, complications might be seen in higher frequency than previously
      reported. Emergency medicine providers and staff must become familiar with
      clinical presentations and management of vaccine complications. In addition,
      policies and procedures must be developed to prevent unimmunized providers from
      inadvertently contacting the active vaccination sites of their patients and, if
      the providers themselves have active vaccination sites, to protect their patients
      and their own families.

PMID- 14581921
TI  - The risks and benefits of pre-event smallpox vaccination: where you stand depends
      on where you sit.

PMID- 14581922
TI  - Removing health care workers from clinical duties after smallpox vaccination: is
      it really necessary?

PMID- 14581923
TI  - Against all advice: an analysis of out-of-hospital refusals of care.
AB  - STUDY OBJECTIVE: We examine the characteristics of patients involved in out-of
      hospital emergency medical services (EMS) incidents that result in refusal of
      care and determine the rates of subsequent EMS, emergency department (ED), and
      inpatient care, as well as death within 7 days. METHODS: Utah statewide EMS data
      identifying refusals of care were probabilistically linked to Utah statewide ED,
      inpatient, and death certificate data within 7 days of the initial EMS refusals
      for 1996 to 1998. Refusals were defined as incidents in which field treatment or
      transport was refused and did not include incidents in which EMS providers deemed
      care or transport unnecessary. RESULTS: Of 277244 EMS incidents, 14109 (5.1%)
      resulted in refusals of care. For all age groups, motor vehicle crash dispatches
      resulted in the highest rate of refusal of care, ranging from 8.0% to 11.7%.
      Slightly more than 3% of patients involved in a refusal of care incident had a
      subsequent EMS dispatch within a week. One fifth of the patients involved in EMS
      refusals of care had a subsequent ED visit. Less than 2% of the EMS refusal
      patients were hospitalized; hospitalization was highest among children younger
      than 3 years and adults older than 64 years. Twenty-five adults died within a
      week of refusing EMS care, of whom 19 (76.0%) were older than 64 years.
      CONCLUSION: Refusal of care incidents are a small segment of all EMS incidents.
      They arise from a variety of situations, and the risk for missed intervention may
      be minimal.

PMID- 14581924
TI  - The Combitube as a salvage airway device for paramedic rapid sequence intubation.
AB  - STUDY OBJECTIVE: The safety of out-of-hospital rapid sequence intubation depends
      on a reliable strategy when orotracheal intubation is unsuccessful. Here we
      describe our experience with the Combitube (esophageal-tracheal twin-lumen airway
      device) as a salvage airway device for paramedic rapid sequence intubation.
      METHODS: The San Diego Paramedic Rapid Sequence Intubation Trial was performed to
      assess the effect of paramedic rapid sequence intubation on outcome in severely
      head-injured patients. Adults with severe head trauma (Glasgow Coma Scale score 3
      to 8) who were unable to be intubated without medications were enrolled.
      Midazolam and succinylcholine were administered, and paramedics were allowed a
      maximum of 3 attempts at orotracheal intubation. If the attempts were
      unsuccessful, Combitube insertion was mandated. After confirmation of tube
      position, rocuronium was given and standard ventilation protocols were used. The
      primary outcome measure for this analysis was the success rate for Combitube
      insertion after unsuccessful orotracheal intubation. In addition, Combitube
      insertion and orotracheal intubation patients were compared with regard to
      demographic, clinical, and outcome data. RESULTS: A total of 426 patients were
      enrolled in the trial, with 420 meeting inclusion criteria for this analysis.
      Orotracheal intubation was successful in 355 (84.5%) of 420; Combitube insertion
      was successful in 58 (95.1%) of 61 attempts, with no reported complications.
      Patients undergoing Combitube insertion had higher Face Abbreviated Injury Scale
      scores and were more likely to have oropharyngeal blood or vomitus. Arrival
      Pco(2) values were higher, and arrival Po(2) values were lower but still
      supranormal in patients undergoing Combitube insertion. There were no mortality
      differences between patients undergoing Combitube insertion and those undergoing
      orotracheal intubation. CONCLUSION: The Combitube can be an effective salvage
      airway device for paramedic rapid sequence intubation in an urban/suburban, high
      volume emergency medical services system with paramedics who are experienced in
      Combitube placement and with stringent protocols for its use. The device should
      be tested in other sizes and types of systems and under less medical scrutiny
      than was used in this study.

PMID- 14581925
TI  - Evidence-based emergency medicine/systematic review abstract: Antibiotic
      treatment for acute maxillary sinusitis.

PMID- 14581926
TI  - Evidence-based emergency medicine/systematic review abstract: Are bronchodilators
      effective in bronchiolitis?

PMID- 14581929
TI  - The human dopamine D4 receptor repeat sequences modulate expression.
AB  - Genetic studies have implicated a polymorphic repeat sequence in exon 3 of the
      human dopamine D4 receptor in various behavioral and psychiatric disorders.
      Functionally various repeat variants are nearly identical, but whether these have
      different effects on gene expression has not been studied. To study the role of
      the repeat sequences on expression independently from its structural and
      functional effects at the protein level, we introduced these sequences
      immediately upstream of the promoter and in the 3' untranslated region of a
      luciferase reporter vector. In this report, we demonstrate that the repeat
      sequence can both modulate promoter activity and alter expression post
      transcriptionally. The repeat sequence can serve as a substrate for a nuclear
      binding factor and all the three repeat variants can suppress promoter activity.
      Placement of the three repeat variants downstream from the luciferase gene in the
      expression vector shows, however, that the D4.7 repeat sequence has significantly
      suppressed expression of the reporter compared to the D4.2 and D4.4 repeats,
      likely via mechanisms involving RNA stability or translational efficiency. These
      data indicate that the various D4 repeat sequences have different effects on
      expression, which may explain its potential role in behavioral disorders.

PMID- 14581930
TI  - Assembly and activation of the gamma-secretase complex: roles of presenilin
      cofactors.

PMID- 14581932
TI  - The molecular genetics of schizophrenia: new findings promise new insights.
AB  - The high heritability of schizophrenia has stimulated much work aimed at
      identifying susceptibility genes using positional genetics. However, difficulties
      in obtaining clear replicated linkages have led to the scepticism that such
      approaches would ever be successful. Fortunately, there are now signs of real
      progress. Several strong and well-established linkages have emerged. Three of the
      best-supported regions are 6p24-22, 1q21-22 and 13q32-34. In these cases, single
      studies achieved genome-wide significance at P<0.05 and suggestive positive
      findings have also been reported in other samples. The other promising regions
      include 8p21-22, 6q21-25, 22q11-12, 5q21-q33, 10p15-p11 and 1q42. The study of
      chromosomal abnormalities in schizophrenia has also added to the evidence for
      susceptibility loci at 22q11 and 1q42. Recently, evidence implicating individual
      genes within some of the linked regions has been reported and more importantly
      replicated. The weight of evidence now favours NRG1 and DTNBP1 as susceptibility
      loci, though work remains before we understand precisely how genetic variation at
      each locus confers susceptibility and protection. The evidence for catechol-O
      methyl transferase, RGS4 and G72 is promising but not yet persuasive. While
      further replications remain the top priority, the respective contributions of
      each gene, relationships with aspects of the phenotype, the possibility of
      epistatic interactions between genes and functional interactions between the gene
      products will all need investigation. The ability of positional genetics to
      implicate novel genes and pathways will open up new vistas for neurobiological
      research, and all the signs are that it is now poised to deliver crucial insights
      into the nature of schizophrenia.

PMID- 14581931
TI  - Erythropoietin: a candidate compound for neuroprotection in schizophrenia.
AB  - Erythropoietin (EPO) is a candidate compound for neuroprotection in human brain
      disease capable of combating a spectrum of pathophysiological processes
      operational during the progression of schizophrenic psychosis. The purpose of the
      present study was to prepare the ground for its application in a first
      neuroprotective add-on strategy in schizophrenia, aiming at improvement of
      cognitive brain function as well as prevention/slowing of degenerative processes.
      Using rodent studies, primary hippocampal neurons in culture, immunohistochemical
      analysis of human post-mortem brain tissue and nuclear imaging technology in man,
      we demonstrate that: (1) peripherally applied recombinant human (rh) EPO
      penetrates into the brain efficiently both in rat and humans, (2) rhEPO is
      enriched intracranially in healthy men and more distinctly in schizophrenic
      patients, (3) EPO receptors are densely expressed in hippocampus and cortex of
      schizophrenic subjects but distinctly less in controls, (4) rhEPO attenuates the
      haloperidol-induced neuronal death in vitro, and (4) peripherally administered
      rhEPO enhances cognitive functioning in mice in the context of an aversion task
      involving cortical and subcortical pathways presumably affected in schizophrenia.
      These observations, together with the known safety of rhEPO, render it an
      interesting compound for neuroprotective add-on strategies in schizophrenia and
      other human diseases characterized by a progressive decline in cognitive
      performance.

PMID- 14581933
TI  - Stress-induced alternative splicing of acetylcholinesterase results in enhanced
      fear memory and long-term potentiation.
AB  - Stress insults intensify fear memory; however, the mechanism(s) facilitating this
      physiological response is still unclear. Here, we report the molecular,
      neurophysiological and behavioral findings attributing much of this effect to
      alternative splicing of the acetylcholinesterase (AChE) gene in hippocampal
      neurons. As a case study, we explored immobilization-stressed mice with
      intensified fear memory and enhanced long-term potentiation (LTP), in which
      alternative splicing was found to induce overproduction of neuronal 'readthrough'
      AChE-R (AChE-R). Selective downregulation of AChE-R mRNA and protein by antisense
      oligonucleotides abolished the stress-associated increase in AChE-R, the
      elevation of contextual fear and LTP in the hippocampal CA1 region. Reciprocally,
      we intrahippocampally injected a synthetic peptide representing the C-terminal
      sequence unique to AChE-R. The injected peptide, which has been earlier found to
      exhibit no enzymatic activity, was incorporated into cortical, hippocampal and
      basal nuclei neurons by endocytosis and retrograde transport and enhanced
      contextual fear. Compatible with this hypothesis, inherited AChE-R overexpression
      in transgenic mice resulted in perikaryal clusters enriched with PKCbetaII,
      accompanied by PKC-augmented LTP enhancement. Our findings demonstrate a primary
      role for stress-induced alternative splicing of the AChE gene to elevated
      contextual fear and synaptic plasticity, and attribute to the AChE-R splice
      variant a major role in this process.

PMID- 14581934
TI  - The relation of obesity throughout life to carotid intima-media thickness in
      adulthood: the Bogalusa Heart Study.
AB  - OBJECTIVE: Although obese children are at increased risk for coronary heart
      disease in later life, it is not clear if this association results from the
      persistence of childhood obesity into adulthood. We examined the relation of
      adiposity at various ages to the carotid intima-media thickness (IMT) at age 35
      y. DESIGN: Prior to the determination of IMT by B-mode ultrasound, subjects (203
      men, 310 women) had, on average, six measurements of body mass index (BMI) and
      triceps skinfold thickness (TSF) between the ages of 4 and 35 y. Mixed regression
      models for longitudinal data were used to assess the relation of these
      characteristics to adult IMT. RESULTS: Overall, adult IMT was associated with
      levels of both BMI and TSF (P<0.001), with the magnitudes of the associations
      with childhood adiposity comparable to those with adult levels of BMI and TSF.
      Furthermore, adult obesity modified the association between childhood adiposity
      and IMT: high IMT levels were seen only among overweight (BMI > or =95th
      percentile) children who became obese (BMI > or =30 kg/m2) adults (P<0.01 for
      linear trend). In contrast, IMT levels were not elevated among (1) overweight
      children who were not obese in adulthood, or among (2) thinner children who
      became obese adults. CONCLUSIONS: These results emphasize the adverse, cumulative
      effects of childhood-onset obesity that persists into adulthood. Since many
      overweight children become obese adults, the prevention of childhood obesity
      should be emphasized.

PMID- 14581935
TI  - The HPCA Act--back to the future.

PMID- 14581936
TI  - At last--some reasonable comments on informed consent.

PMID- 14581937
TI  - Adverse events in New Zealand healthcare.

PMID- 14581938
TI  - Adverse events in New Zealand public hospitals II: preventability and clinical
      context.
AB  - AIMS: To assess the preventability and clinical context of adverse events
      identified in New Zealand public hospitals. METHODS: Two-stage retrospective
      review of 6579 medical records randomly sampled from admissions for 1998 in 13
      generalist hospitals providing acute care. Initial screening and medical review
      according to a standardised protocol. RESULTS: Eight hundred and fifty adverse
      events were identified, of which over one third (315) were preventable to a
      significant degree. Preventability of events increased with age of patient, and
      was more characteristic of certain diagnostic categories. Half of all events
      (413/850) were both preventable and occurred in hospital, giving an occurrence
      rate of 6.3%. This rate increased with patient age, as did impact on patients and
      extended stay. There were also variations by diagnostic category. Over half of
      the events were associated with surgery (489) and one third with medicine (303);
      operative incidents were predominant in the former, drug-related in the latter,
      and system issues in both. Events in medicine had greater patient impact, and
      were less likely to have occurred in a public hospital. System errors featured
      prominently as an area for prevention, being associated with nearly half of all
      preventable in-hospital events. Consultation and education were also important,
      resources less so. CONCLUSIONS: Preventable adverse events have a major impact on
      patient outcomes and extended hospital stay. A substantial proportion of these
      are system related and, hence, in principle susceptible to quality improvement.

PMID- 14581939
TI  - The characteristics of doctors receiving medical complaints: a cross-sectional
      survey of doctors in New Zealand.
AB  - AIM: To analyse the incidence and characteristics of medical complaints received
      by doctors in New Zealand. METHODS: A cross-sectional survey of New Zealand
      doctors randomly selected from each of three groups from the New Zealand medical
      register: vocationally registered general practitioners; vocationally registered
      hospital-based specialists; and general registrants. RESULTS: Nine hundred and
      seventy one doctors (11% of registered New Zealand doctors) indicated that 34%
      had ever received a medical complaint, and 66% had never received one. The rate
      of complaint in New Zealand is rising. The annual rate of complaint in 2000 was
      5.7%, with doctors in the 40-60 age group receiving 68% of complaints. Doctors
      who were male, vocationally registered general practitioners, and holding higher
      postgraduate qualifications were more likely to receive a complaint. Time to
      resolution of a complaint is long, with 74% of dismissed and 59% of upheld
      complaints being resolved within 12 months. CONCLUSIONS: This study finds a high
      incidence of complaint in New Zealand. It finds differences between doctors based
      on gender, qualification, and field of practice, and suggests that responsibility
      for patient care may be an important determinant of the risk of receiving a
      complaint.

PMID- 14581940
TI  - The demographic characteristics of New Zealand medical students: the New Zealand
      Wellbeing, Intentions, Debt and Experiences (WIDE) Survey of Medical Students
      2001 study.
AB  - AIMS: To develop and administer the first nationwide survey of all medical
      students in New Zealand. This paper reports the demographic characteristics of
      medical students and compares them with the general population. METHODS: A
      questionnaire was developed, with questions modelled on the New Zealand Census,
      and administered to all New Zealand medical students. Data were then compared
      with the New Zealand Census. RESULTS: The response rate was 83%. Female students
      made up 55.9% of the class. The ethnic composition of the class, Maori (6.8%),
      Pacific Islander (4.3%), NZ European (50.9%), Asian (31.4%), differed
      significantly from the general New Zealand population. Maori and Pacific Island
      students, and students from a rural background were significantly under
      represented. Permanent residents represented 11.1% of the student population.
      Three quarters of medical students reported that at least one of their parents
      had a tertiary qualification. CONCLUSIONS: Medical students are more likely to be
      socioeconomically advantaged and from an urban community, and less likely to be
      of Maori or Pacific Island descent, than the general population. In the context
      of a shortage of practitioners in rural, lower socioeconomic and Maori or Pacific
      Island areas, these differences are worrying. The number of permanent residents
      and female students may have implications for the New Zealand medical workforce.

PMID- 14581941
TI  - Unicompartmental knee arthroplasty: is it durable?
AB  - AIM: To analyse the long-term durability of unicompartmental knee arthroplasties
      using the Marmor/Mod 2 prosthetic. METHODS: Survivorship analysis was used to
      retrospectively evaluate 113 medial unicompartmental knee arthroplasties
      performed between 1974 and 1989 in two New Plymouth hospitals. An outcome was
      determined for every case. RESULTS: The survival rate was 95% at 10 years and 85%
      at 15 years. All 27 knees surviving at the time of the study were assessed
      clinically using the Knee Society Score, and 25 of the 27 knees underwent
      radiographic evaluation. The Knee Society Knee and Knee Society Functional scores
      were 72 points and 56 points respectively for the group of 27 surviving
      prostheses, and the 25 knees X-rayed showed no loosening or fracture of the
      prosthesis. CONCLUSIONS: Unicompartmental knee arthroplasty with the Marmor/Mod 2
      prosthesis has provided satisfactory long-term durability in this cohort of
      elderly patients, in comparison with similar published studies featuring other
      prostheses.

PMID- 14581942
TI  - Informed consent in New Zealand: medical myths.

PMID- 14581943
TI  - Shame, guilt and the medical practitioner.
AB  - The underlying positivist philosophy of medicine and the emphasis on 'knowing'
      can induce a shame response when doctors perceive they have failed. In contrast
      to guilt, shame affects the whole of the self and may diminish the doctor's
      ability to accept his or her own illness, respond to a disciplinary complaint, or
      consider clinical supervision. Consideration of the polarities of practice can
      help doctors respond to mistakes, errors, or wrongdoing with guilt rather than
      with shame. This places a perceived failure outside the self of the doctor,
      enabling restoration of relationships and learning from clinical experience. This
      will benefit both doctors and patients.

PMID- 14581944
TI  - Negative betahCG: positive ectopic pregnancy.

PMID- 14581945
TI  - Delayed diagnosis of steroid-induced colon diverticulum perforation.

PMID- 14581946
TI  - Antibiotic susceptibility of Haemophilus influenzae isolates from four New
      Zealand sites.

PMID- 14581947
TI  - Inappropriate prescription of methylphenidate.

PMID- 14581948
TI  - Can a patient be informed without also understanding?

PMID- 14581949
TI  - OOS or MUD: unclear thinking is the problem.

PMID- 14581951
TI  - Improving quality (IQ): a systems approach for the New Zealand health and
      disability sector.

PMID- 14581950
TI  - Opponents of DTCA need the objectivity they expect of advertisers.

PMID- 14581952
TI  - Adults' perceptions of the causes and primary prevention of common fatal cancers
      in New Zealand.
AB  - AIMS: To assess population perceptions of the causes and primary prevention of
      common fatal cancers, and to help inform the New Zealand Cancer Control Strategy.
      METHODS: A national telephone survey obtained perceptions from a random
      population sample, 20 years or older, identified from telephone directory
      listings, supplemented with self-identified Maori from electoral rolls. Quotas
      were set to recruit population proportions consistent with 1996 Census
      distributions. RESULTS: The 438 respondents (64% participation) matched 1996
      Census distributions for age, sex and ethnicity, but were socioeconomically
      advantaged. Among women, breast, cervical and lung cancer were most salient;
      among men, prostate, lung and bowel cancer - partially congruent with population
      statistics. There was high unprompted awareness that tobacco smoke and sun
      exposure affect lung cancer and skin cancer risk, respectively, but less
      awareness of potential protective strategies for other cancers. CONCLUSIONS:
      Perceptions of cancer risk and prevention are affected by high-profile
      programmes. Cancer prevention activities should reflect known risks and the
      potential for prevention. With high incidence and death rates and potentially
      modifiable risks, bowel cancer deserves greater attention. A comprehensive cancer
      prevention strategy needs to go beyond raising awareness and the promotion of
      individual behavioural change to the development of healthy public policies and
      practices that create supportive environments for health-promoting behaviours.

PMID- 14581953
TI  - Equestrian injuries in New Zealand, 1993-2001: knowledge and experience.
AB  - AIMS: The aims of this study were to investigate the extent of equestrian
      injuries in New Zealand and provide a range of prevention interventions. METHODS:
      An examination of New Zealand Health Information Service (NZHIS) morbidity data
      for 1993 to 2001 and mortality data for 1993 to 1999 was undertaken. Recent
      studies on equestrian injuries were evaluated. RESULTS: NZHIS data indicated that
      as a result of horse-related injuries 5613 people were hospitalised between 1993
      and 2001 and there were 16 fatalities between 1993 and 1999. Horse-related
      injuries were most prevalent in young females aged 10 to 19 years. Among Maori
      (the indigenous people of New Zealand), men predominated in horse-related injury
      numbers. Overall, half of equestrian injuries occurred in those under the age of
      19 years. The major injury site was the arm. High equestrian-injury rates were
      recorded in rural regions. CONCLUSIONS: The findings indicate that age and
      regionally specific practical injury prevention strategies, health promotion
      messages and educational programmes are required. In particular, clear rules and
      regulations on protective and safety clothing are likely to enhance safety.
      Education in horse behaviour is required to facilitate safer environments on and
      around horses. A code of practice for horse riding and trekking establishments
      could decrease the risk of injury to those who hire horses.

PMID- 14581954
TI  - A comparative study of drug utilisation at different levels of the primary
      healthcare system in Kaski district, Western Nepal.
AB  - AIMS: Studies that compare prescribing patterns at different levels of the
      primary healthcare system are lacking in Western Nepal. The present study was
      undertaken to obtain information on age, sex distribution, and morbidity profiles
      of patients, prescribing patterns and defined daily dose of commonly used drugs.
      METHODS: The study was carried out over a three-month period (1 June 2000 to 31
      August 2000) at four centres in the Kaski district, Western Nepal. Chi-square
      test was used to compare differences in morbidity profiles and prescribing
      patterns (p <0.01). RESULTS: There were significant differences in the average
      number of drugs per prescription across different levels. The morbidity profiles
      were also different. Vitamins were more commonly prescribed at the primary health
      centre level. Antibiotics were prescribed in 67% of encounters at the level of
      primary health centre, but the prescribing decreased at the levels of health post
      and sub-health post. CONCLUSIONS: The average number of drugs per prescription
      and the average cost were higher at the primary health centre level and this may
      be due to the increased prescribing frequency of vitamins and tonics. Comparisons
      of prescribing patterns at different levels of healthcare, and between government
      and private healthcare institutions, are urgently required.

PMID- 14581955
TI  - Pre-hospital antibiotic treatment of meningococcal disease: scope for
      improvement.
AB  - AIM: To determine the extent to which Auckland general practitioners (GPs) follow
      Ministry of Health guidelines recommending the administration of pre-hospital
      antibiotic treatment to suspected cases of meningococcal disease. METHODS:
      Retrospective audit of notified cases of meningococcal disease referred by
      Auckland GPs from 1 May 2001 to 30 April 2002. RESULTS: Of 142 meningococcal
      disease cases that were referred to hospital by GPs, 111 (78%) were 'eligible' or
      met Ministry of Health guideline criteria for pre-hospital antibiotic treatment.
      Of these, only 33 (30%) were given parenteral antibiotics. Those with a rash were
      twice as likely as those without a rash to receive antibiotics (RR 2.1; 95% CI
      1.7-2.7). There was no difference in antibiotic administration by age, sex,
      ethnicity, or where there was an estimated delay of greater than 30 minutes to
      assessment in hospital. CONCLUSIONS: The findings of this audit reinforce the
      need for GPs to have a higher index of suspicion and lower threshold for
      treatment for suspected cases of meningococcal disease and to give antibiotics
      more often than they do at present.

PMID- 14581956
TI  - Anxious about electronic health records? No need to be.
AB  - Every day the takeover of paper records by electronic versions seems more
      inevitable. Many of us who have used the paper version, despite its limitations,
      are anxious about new technology with its different challenges. In this paper we
      discuss aspects of both types of record and identify some of their weaknesses and
      strengths. Whilst there is little science to support one version over the other,
      the health industry is undoubtedly moving to adopt an electronic record. In
      writing this paper we aim to reassure clinicians that the electronic record is,
      on balance, likely to enhance the quality of their professional practice.

PMID- 14581957
TI  - Hiccup in patients with advanced cancer successfully treated with gabapentin:
      report of three cases.

PMID- 14581958
TI  - Splenic rupture occurring as a complication of subacute bacterial endocarditis.

PMID- 14581959
TI  - Direct-to-consumer advertising is more profitable if it is misleading.

PMID- 14581960
TI  - DTCA not real advertising issue.

PMID- 14581962
TI  - Quality improvement: time for radical thought and measurable action.

PMID- 14581961
TI  - More on prostate cancer screening.

PMID- 14581963
TI  - Plagiocephaly--more questions than answers.

PMID- 14581964
TI  - The Safe-T-Sleep device: safety and efficacy in maintaining infant sleeping
      position.
AB  - AIMS: The issue of infant sleeping position has socio-political ramifications.
      Current recommendations endorse supine sleeping as an aid to reducing the risk of
      sudden infant death syndrome (SIDS). Persistent sleeping of a newborn infant in
      the same position may induce plagiocephaly without synostosis (PWS). Parents in
      our craniofacial clinic, whose children present with PWS, often feel torn between
      apparently conflicting goals--avoiding SIDS and avoiding PWS. The Safe-T-Sleep
      device, a form of infant sleep wrap, purportedly allows safe semi-supine
      positioning, thus ameliorating PWS (by preventing the infant from lying on the
      cranial 'flat spot') while not increasing the risk of SIDS. Before recommending
      the device to parents in our plagiocephaly clinics, we designed a prospective,
      hospital-based trial to assess the safety and efficacy of the device in
      maintaining selected sleeping positions. This was not a trial of the efficacy of
      the Safe-T-Sleep device in treating plagiocephaly. METHODS: The devices were
      trialed on 31 babies, between birth and 11 months of age. A total of 396 hours of
      observations were recorded. RESULTS: The device maintained the selected body
      position in 94% of recorded observations and head position in 87%. There were no
      significant adverse events or complications associated with the use of the Safe-T
      Sleep device. CONCLUSIONS: The device appears to be safe and effective. It is now
      being advocated in our clinic as an aid to active counter-positioning strategies
      to passively correct incipient or established positional plagiocephaly in younger
      babies.

PMID- 14581965
TI  - Resuscitation teaching in New Zealand schools.
AB  - AIMS: Resuscitation skills such as cardiopulmonary resuscitation (CPR) are taught
      as an optional component of the New Zealand school curriculum. This study was
      conducted to determine the frequency of, and factors influencing, CPR teaching in
      New Zealand primary and secondary schools. METHODS: At the end of the 2001 school
      year, we surveyed by questionnaire every school in New Zealand asking which
      schools taught CPR skills during 2001, what other resuscitation skills were
      taught, and what the barriers to greater teaching of resuscitation were. RESULTS:
      Seven hundred and fifty four of 2205 (34.9%) primary schools and 173 of 456
      (38.6%) secondary schools returned the survey. Of primary schools, 37.5% taught
      resuscitation skills during 2001, as did 81% of secondary schools. In secondary
      schools, resuscitation was most commonly taught during year 12 (pupil age 16-17
      years), but then only as an elective subject to 10-30% of students. For both
      primary and secondary schools there was a positive correlation between school
      size (number of pupils) and the teaching of resuscitation (p = 0.0001). The most
      significant barriers to resuscitation teaching were identified as funding, an
      overfull curriculum and, in primary schools, the question of the suitability of
      teaching resuscitation to young children. CONCLUSIONS: This survey indicates that
      the majority of primary schools are not teaching CPR skills, or other life-saving
      first aid, and that the majority of secondary schools are treating these subjects
      as optional, taught only to a small proportion of students. If New Zealand is to
      achieve widespread community CPR knowledge, it is suggested that greater funding
      needs to be available to schools for resuscitation/first-aid training and the
      subject must become a compulsory, rather than optional, component of the school
      curriculum.

PMID- 14581966
TI  - Current practice for anticoagulation prophylaxis in inguinal hernia surgery: a
      questionnaire survey.
AB  - AIMS: The incidence of deep vein thrombosis (DVT) and pulmonary embolism (PE) is
      well documented in patients undergoing surgery involving general anaesthesia. A
      large number of trials have been conducted establishing the efficacy of
      prophylactic measures against deep vein thrombosis, yet there remains wide
      practice variation amongst surgeons regarding the use of anticoagulation
      measures. The main aims of our study were to survey the use of DVT prophylaxis
      for inguinal hernia repairs in the UK, and to establish any variations amongst
      British surgeons in their use of anticoagulation measures for repair of inguinal
      hernias. METHODS: We conducted a questionnaire survey amongst surgeons of the
      Association of Endoscopic Surgeons of Great Britain and Ireland (AESGBI). Two
      hundred and fifty questionnaires were sent with a response rate of 72%. RESULTS:
      Our results have shown wide variation amongst British surgeons in the use of
      anticoagulation measures. Furthermore, only 10% of the surgeons in the
      laparoscopic and 14% in the open group risk stratify their patients; 10% of the
      surgeons do not use any DVT prophylaxis at all. CONCLUSIONS: Although the
      incidence of DVT in inguinal hernia repair is very low this is a very commonly
      performed procedure. Both over and under treatment with thromboprophylaxis can
      have implications in terms of side effects and costs. One possible way to avoid
      problems is to risk stratify patients before thromboprophylaxis is instituted.

PMID- 14581967
TI  - Correction of deformational auricular anomalies by moulding--results of a fast
      track service.
AB  - AIM: To report on the result of a fast-track referral service in treating
      deformational auricular anomalies using moulding therapy, by employing nurses who
      were familiar with the indications and technique, working in close liaison with
      plastic surgeons. METHODS: A deformational auricular anomaly is defined as an ear
      having normal chondrocutaneous components but an abnormal architecture;
      therefore, it can be manipulated digitally to a normal shape. Having demonstrated
      the value of auricular moulding therapy to our neonatal practitioners, we
      established a fast-track referral and treatment protocol for infants with
      deformational auricular anomalies. Treatment was initiated promptly by one of
      four nurses. The type and severity of the auricular anomaly were documented both
      clinically and photographically before and three months following cessation of
      treatment. Assessment of the results was made by comparing the pre- and post
      treatment photographs and by a postal questionnaire, which was dispatched to the
      parents of the patients three months after treatment was discontinued. RESULTS:
      Sixteen male and 14 female patients, aged between one day and 15 weeks (mean 24
      days) with 44 deformational auricular anomalies, underwent moulding therapy.
      Complete correction or marked improvement was achieved in 26 patients (87%) with
      38 ears (86%) while slight or no improvement occurred in 4 patients (6 ears),
      following one to 14 (mean 7) weeks of moulding. Questionnaires were returned by
      the parents of 24 patients (80%). According to the parents' assessment, complete
      correction or marked improvement occurred in 29 of 35 anomalous ears (83%) in 20
      of these 24 patients (83%). All parents felt that auricular moulding was
      worthwhile. CONCLUSIONS: Deformational auricular anomalies should be treated non
      surgically with moulding therapy. For this treatment to be effective, it should
      be initiated in the first three months of life. Parental persistence with the
      treatment is essential for a satisfactory outcome. A fast-track referral service,
      employing nurses who form the first point of contact and work in close
      association with a plastic surgery service, is an effective treatment strategy
      that will largely negate the need for surgical correction of deformational
      auricular anomalies.

PMID- 14581968
TI  - Spontaneous coronary artery dissection: a report of two cases occurring during
      menstruation.

PMID- 14581969
TI  - Drotrecogin alfa (recombinant human activated protein C) in severe sepsis--a New
      Zealand viewpoint.
AB  - AIM: Sepsis is a serious and increasing worldwide intensive care problem. In
      response to intensivists' concerns over the benefits, risks and financial
      implications of the use of drotrecogin alfa (recombinant human activated protein
      C), the first adjunctive therapy for sepsis licensed in New Zealand, the New
      Zealand Region of the Australian and New Zealand Intensive Care Society (ANZICS)
      requested an advisory statement from a working party of New Zealand intensivists.
      METHODS: We reviewed (a) the PROWESS study of drotrecogin alfa recombinant; (b)
      the submission made by the sponsoring company to the FDA; (c) recent discussions
      and an economic evaluation of the use of the agent; (d) Australian pharmaceutical
      benefits scheme positive recommendations; (e) guidelines produced by the Eli
      Lilly Australian Advisory Board; (f) Australian hospital decisions on
      availability; and (g) New Zealand pricing and payment arrangements. We then
      formulated suggested New Zealand guidelines. RESULTS: We recommend that hospital
      pharmacy and therapeutics committees review the agent now. If the agent is made
      available for use, we recommend that: (a) specialists prescribing the agent be
      required to contribute clinical data to a national register of patients, (b)
      patients considered for treatment should first be treated with all appropriate
      surgical and medical therapy for severe sepsis with high illness severity in an
      intensive care unit by an intensivist; (c) patients considered for treatment
      should not have severe comorbidity or predetermined treatment limitations or
      contraindications to the agent in the original phase III study; and (d) patients
      should be considered only if seen to be not clearly improving after a six-hour
      period of intensive treatment. Once a decision has been made to treat with
      drotrecogin alfa, treatment should commence as soon as possible and within 24
      hours of meeting criteria. Although the agent is recommended for use in adults,
      it may be reasonable to treat some older children. CONCLUSIONS: Despite high cost
      and moderate benefit, it may be reasonable to treat highly selected New Zealand
      patients with drotrecogin alfa.

PMID- 14581970
TI  - Two brothers with nail cyanosis.

PMID- 14581971
TI  - Ban on DTCA represents State takeover.

PMID- 14581972
TI  - Direct-to-consumer advertising--yes it can compromise patient health.

PMID- 14581973
TI  - NZ must not return to the pre-PSA era.

PMID- 14581975
TI  - Effects of male circumcision on female arousal and orgasm.

PMID- 14581974
TI  - OOS or MUD.

PMID- 14581976
TI  - New Zealand deserves better. Direct-to-consumer advertising (DTCA) of
      prescription medicines in New Zealand: for health or for profit?

PMID- 14581978
TI  - Direct-to-consumer advertising--where does the public interest lie?

PMID- 14581980
TI  - What do we need to do to reduce smoking among teenagers?

PMID- 14581981
TI  - Haemophilia treatment: where to from here? Have the risks increased?

PMID- 14581982
TI  - Smoke-free schools? Results of a secondary school smoking policies survey 2002.
AB  - AIM: To describe the cigarette-smoking policies of a sample of New Zealand
      secondary schools. METHODS: Schools randomly selected from six geographical
      regions for participation in the Health Sponsorship Council's 2002 Youth
      Lifestyle Study (YLS) were invited to also participate in the School Smoking
      Policies Survey (SSPS). RESULTS: Eighty one of 82 schools responded (response
      rate 98.8%); 64 schools (79.0%) provided copies of smoking policies. Of the
      schools that provided policies, only 31 (50.8%) were totally smoke free, ie,
      banned smoking 24 hours a day, seven days a week. Five schools (8.2%) were both
      smoke free and fully compliant with existing legislation. Seventy eight schools
      (96.3%) provided education about smoking and imposed sanctions on students caught
      smoking. Most respondents (74.1%) considered school staff would support proposed
      changes to the Smoke-free Environments Act that would make all school buildings
      and grounds totally smoke free. CONCLUSIONS: Most secondary schools are not smoke
      free, but most staff are likely to support smoke-free status. Existing
      inconsistency among educational messages, school practice and staff actions may
      undermine tobacco-smoking-prevention efforts. Proposed strengthening of smoke
      free legislation is both timely and necessary to ensure that all New Zealand
      students are provided with totally smoke-free school environments, consistent
      with health education messages.

PMID- 14581983
TI  - The challenge arising from the cost of haemophilia care: an audit of haemophilia
      treatment at Auckland Hospital.
AB  - AIMS: To compare treatment patterns in adults and children with haemophilia and
      to estimate the financial impact of the changing practice of haemophilia care.
      METHODS: A retrospective audit of replacement coagulation factor usage in all
      patients with haemophilia treated at the Auckland Haemophilia Centre during 2001.
      RESULTS: A total of 69 males with haemophilia were included in the audit. Twelve
      children under 16 years old (nine on recombinant products) and six adults (all on
      plasma products) received prophylactic treatment. The remaining patients used
      treatment on demand. The cohort included eight patients with factor VIII
      inhibitors. The estimated cost of replacement products used was around 3 million
      dollars for the 23 children and 2.2 dollars million for the 46 adults.
      CONCLUSIONS: Children with severe haemophilia are predominantly treated with
      recombinant products on regular prophylaxis, whereas adults are largely treated
      on demand with plasma-derived products. This is in line with international
      practice as regular prophylaxis has been shown to improve the quality of life for
      people with haemophilia and in the long term is cost effective. The problem in
      the short term is that prophylaxis is significantly more expensive than on-demand
      treatment. We estimate that the cost of replacement product will increase by at
      least 5% per annum as the children with haemophilia grow.

PMID- 14581984
TI  - Screening for diabetic retinopathy using the mobile retinal camera: the Waikato
      experience.
AB  - AIM: To report the results of the Waikato Regional Mobile Diabetic Retinopathy
      Photoscreening Programme. METHODS: We audited the results of a diabetic retinal
      photoscreening programme using the mobile retinal camera in the Waikato region
      for the period August 1993 to December 2001. RESULTS: A total of 8172 patients
      were screened one or more times, with a total of 15 555 photoscreens,
      representing approximately 79% of the expected number of patients with diabetes
      for the region. Seventy eight per cent showed no diabetic retinopathy (NDR), 9.3%
      had evidence of non-vision-threatening retinopathy (NVR), and 3.1% had evidence
      of vision-threatening retinopathy (VTR). A further 2281 (14.7%) led to a referral
      to an eye clinic for specialist review. The percentage of all screening episodes
      resulting in VTR fell from 11.5% in 1993 to 1.5% in 2002. The overall failure-to
      attend rate for photoscreening was high (18.7%), especially in the Maori
      population (32.3%). CONCLUSION: Mobile retinal photoscreening is practical in a
      large rural area, and its implementation has been associated with a reduction in
      presentations with vision-threatening retinopathy within the total community. The
      rate of subsequent development of VTR in the group with normal eyes on initial
      photoscreening was low and supports a two-yearly repeat photoscreening schedule
      for this group. Despite significant efforts to improve physical access to
      photoscreening, the failure-to-attend rates in all ethnic groups other than
      Europeans are disappointingly high.

PMID- 14581986
TI  - Necrotising fasciitis in neonates: a multidisciplinary approach.

PMID- 14581985
TI  - Differential prescribing of inhaled corticosteroids in New Zealand general
      practice.
AB  - AIM: To determine how inhaled budesonide, beclomethasone and fluticasone are
      prescribed by general practitioners in New Zealand. METHODS: Retrospective study
      of computerised clinical records from 42 general practices in New Zealand for the
      period 1 July 1997 to 30 June 1998. The study population comprised 174 929
      consulting patients, of whom 9878 patients were prescribed budesonide,
      fluticasone, or beclomethasone with full dosing instructions. RESULTS: The mean
      daily prescribed dose was higher for patients receiving inhaled budesonide (886
      microg) than beclomethasone (547 microg), a difference of 339 microg (95% CI 311
      microg to 367 microg), and fluticasone (508 microg), a difference of 378 microg
      (95% CI 344-412). The difference between mean daily prescribed doses of
      beclomethasone and fluticasone was 39 microg (95% CI 15-63). The overall
      difference was consistent across age groups and with different types of
      inhalation device. Evidence of systematic prescribing of higher doses of
      budesonide to patients with more severe asthma was not found. Patients prescribed
      fluticasone were more likely to have been prescribed oral steroids in the
      preceding year. CONCLUSIONS: Conclusions about the relative potencies of inhaled
      corticosteroids cannot be made with the data presented. However, data presented
      show that inhaled corticosteroids have not been prescribed in line with their
      reported relative potencies. This study provides benchmark data for the
      prescribing of inhaled steroids in New Zealand general practice.

PMID- 14581987
TI  - Who attends an outpatient eye clinic and how do they get there?

PMID- 14581988
TI  - Long-term maternal outcome after pregnancy in women with diabetic nephropathy.

PMID- 14581989
TI  - Post-dural-puncture headache in a seven-month-old boy?

PMID- 14581990
TI  - Migration, mobility and the exposure fallacy: an issue for New Zealand.

PMID- 14581991
TI  - Theoretical and methodological studies of continuous microbial bioreactors.
AB  - This article reviews most of the author's studies on process development and
      reactor design for continuous microbial reactions. (1) Enzyme reactions of
      growing and non-growing microbial cells immobilized in agar gel beads were
      analyzed pertaining to the effects of external and internal diffusion of
      substrate on reaction kinetics. (2) Experimental correlations of production rates
      of beta-fructosidase and acid phosphatase with dilution rate of continuous
      culture were simulated based on an operon model for enzyme regulation. (3)
      Population dynamics of an amylase-producing bacteria and their mutant were
      discussed in relation to enzyme productivity in a continuous culture of spore
      forming bacteria. (4) Plasmid mobilization in a mixed population of donor,
      recipient, and helper cells was investigated in a continuous culture as a model
      study of accidental release of a genetically modified plasmid into a natural
      environment. (5) A production rate increase of up to 100-fold was achieved by
      cell-recycle culturing of continuous acetic acid fermentation using a filter
      module with a hollow fiber membrane. (6) The feasibility of a continuous surface
      culture for the biooxidation of organic substances was ascribed to an enhanced
      oxygen absorption rate in the presence of a microbial film on a liquid surface.
      (7) Simultaneous separation of inhibitory products using an electrodialysis
      module during some organic acid fermentations was effective for increasing
      production in a continuous culture.

PMID- 14581992
TI  - Effect of support materials on antibiotic MSW2000 production by immobilized
      Streptomyces violatus.
AB  - The production of an antibiotic by free and immobilized cells of Streptomyces
      violatus through entrapment or adsorption on different materials was
      investigated. S. violatus entrapped in Ca-alginate beads gave low antibiotic
      activity compared to the free cell or adsorbed cell, while the adsorption of S.
      violatus on sponge cubes yielded the highest antibiotic concentration after 4
      days of incubation in static cultures. A starch concentration of 10 g/L was
      optimum for the production of the antibiotic by adsorbed cells. The weight and
      size of the sponge cubes used for immobilization influenced production of the
      antibiotic and the optimum weight and size of the sponge were 0.8 g and 1.0
      cm(3), respectively, yielding a maximum antibiotic production of 280 mg/ml.
      Maximum antibiotic production was obtained at an initial pH value of 7.5 and in
      an inoculum size of 3 ml (spore suspension) per 50 ml. The production of the
      antibiotic in a fixed-bed bioreactor reached a maximum value after 2 days of
      incubation at a circulation rate of 30 ml/h. The immobilized cells in the
      bioreactor were reused seven successive times over a period of 14 days.

PMID- 14581993
TI  - A possible role of cellulose-binding protein A (CBPA) in the adhesion of
      Eubacterium cellulosolvens 5 to cellulose.
AB  - The cellulose-binding protein A (CBPA) of Eubacterium cellulosolvens 5 is a
      modular enzyme comprised of a catalytic domain, a cellulose-binding domain and a
      cell wall-binding domain. Cellobiose-grown cells changed their adhesion ability
      to cellulose depending on the growth phase. On the other hand, carboxymethyl
      cellulose (CMC)-grown cells bound to cellulose regardless of their growth phase.
      The distribution of CBPA in the culture supernatant and cell fractions changed
      depending on the carbon source contained in the medium and growth phase. The
      cellobiose-grown cells harvested from the culture of the late stationary growth
      phase did not bind to cellulose, but their adhesion ability was recovered by
      treatment with recombinant CBPA. Moreover, cellobiose-grown cells harvested from
      the culture of an early exponential growth phase bound to cellulose, but their
      adhesion ability was inhibited by treatment with anti-CBPA antiserum. CBPA
      rapidly decreased the viscosity of CMC, indicating that CBPA was endoglucanase.
      The results obtained in this study indicate that CBPA plays an important role in
      the adhesion of E. cellulosolvens 5 cells to cellulose.

PMID- 14581994
TI  - Submerged cultures of Geotrichum candidum and Penicillium camembertii on amino
      acids and glucose.

PMID- 14581995
TI  - Characterization and identification of Acinetobacter strains from clinical
      specimens in Thailand.

PMID- 14581997
TI  - Implications of anemia in human immunodeficiency virus, cancer, and hepatitis C
      virus.
AB  - Anemia is a multifactorial problem in patients with human immunodeficiency virus
      (HIV) infection, cancer, and hepatitis C virus (HCV) infection. New insights
      regarding anemia symptoms and quality of life (QOL) have prompted reassessment of
      traditional triggers for anemia treatment to increase hemoglobin (Hb) and improve
      QOL. In HIV-positive patients, anemia is independently associated with disease
      progression and survival. Many HIV-positive patients receiving highly active
      antiretroviral therapy (HAART) still develop mild to moderate anemia and
      associated QOL impairment. Epoetin alfa effectively increases Hb and improves QOL
      in these patients. Many HIV-positive patients are coinfected with HCV. Standard
      HCV therapy (interferon alfa/ribavirin) can cause anemia that may result in
      treatment alterations and compromised virologic outcome. Epoetin alfa therapy in
      anemic HCV patients increases Hb levels and may provide other benefits.
      Neuroprotective effects of epoetin alfa in preclinical models of central nervous
      system disorders have recently been demonstrated, implying a new therapeutic role
      for this cytokine.

PMID- 14581996
TI  - Superoxide dismutase produced by soil bacteria increases bacterial colony growth
      from soil samples.

PMID- 14581998
TI  - Anemia and survival in human immunodeficiency virus.
AB  - The prospective, multicenter cohort study EuroSIDA has previously reported on
      predictors and outcomes of anemia in patients infected with human
      immunodeficiency virus. In a Cox proportional-hazards model with serial measures
      of CD4+ cell count, plasma viral load, and degrees of anemia fitted as time
      dependent variables, the relative hazard of death increased markedly for patients
      with anemia versus no anemia. A clinical scoring system was developed and
      validated for patients receiving highly active antiretroviral therapy using the
      most recent laboratory measures. Mild and severe anemia were independently
      (P<.01) associated with clinical disease progression, with a relative hazard of
      disease progression of 2.2 (95% confidence interval [CI], 1.6-2.9) and 7.1 (95%
      CI, 2.5-20.1), respectively, compared with patients with no anemia. The
      mechanisms underlying why hemoglobin is such a strong prognostic marker and
      whether correction of anemia itself results in a better prognosis remain to be
      determined.

PMID- 14581999
TI  - Anemia in the setting of cancer and human immunodeficiency virus.
AB  - Anemia commonly occurs in patients with cancer or human immunodeficiency virus
      (HIV) infection as a result of the disease, its treatment, or both. The negative
      impact of anemia on patient quality of life (QOL), functional status, and
      treatment outcomes underscores the need for its correction in these patients. In
      anemic patients with cancer or HIV infection, treatment with epoetin alfa
      increases hemoglobin (Hb) levels, decreases transfusion requirements, and
      improves QOL. In both settings, the gains in overall QOL have been significantly
      and directly related to increases in Hb, with maximum QOL gains in the range of
      Hb levels of 11-13 g/dL, supporting the need to achieve and maintain Hb levels >
      or =12 g/dL in an effort to preserve and maximize QOL benefits. A potential
      survival benefit has also been associated with correction of anemia in patients
      with HIV infection--and possibly in those with cancer as well.

PMID- 14582000
TI  - Anemia in the treatment of hepatitis C virus infection.
AB  - Hepatitis C virus (HCV) infection is a significant worldwide health care problem.
      Nearly one-third of all patients infected with human immunodeficiency virus (HIV)
      are coinfected with HCV. Compared with HIV-monoinfected persons, coinfected
      individuals experience more rapid progression of fibrosis and higher incidence of
      cirrhosis and death as a result of liver disease. Treatment for HCV infection
      includes ribavirin (RBV) plus interferon alfa (IFN-alpha) or pegylated IFN, a
      combination treatment associated with anemia that may require RBV dose reduction
      or discontinuation. IFN-RBV-associated anemia is more profound among coinfected
      patients, who have a high prevalence of pretreatment anemia and may also be
      taking other medications causing anemia. Epoetin alfa administration to HCV
      infected patients with IFN-RBV-related anemia can significantly increase
      hemoglobin levels and maintain significantly higher RBV doses compared with
      patients treated with RBV dose reduction alone. Higher RBV doses and adherence to
      HCV therapy have been associated with higher sustained virologic response (SVR)
      rates. Maintenance of RBV dose with epoetin alfa may improve adherence, thereby
      affecting SVR.

PMID- 14582001
TI  - Central nervous system frontiers for the use of erythropoietin.
AB  - Recombinant human erythropoietin (r-HuEPO; epoetin alfa) is well established as
      safe and effective for the treatment of anemia. In addition to the erythropoietic
      effects of endogenous erythropoietin (EPO), recent evidence suggests that it may
      elicit a neuroprotective effect in the central nervous system (CNS). Preclinical
      studies have demonstrated the presence of EPO receptors in the brain that are up
      regulated under hypoxic or ischemic conditions. Intracerebral and systemic
      administration of epoetin alfa have been demonstrated to elicit marked
      neuroprotective effects in multiple preclinical models of CNS disorders. Epoetin
      alfa has also been shown to prevent the loss of autoregulation of cerebral blood
      flow in a model of subarachnoid hemorrhage. The mechanisms of EPO-induced
      neuroprotection include prevention of glutamate-induced toxicity, inhibition of
      apoptosis, anti-inflammatory effects, antioxidant effects, and stimulation of
      angiogenesis. Collectively, these findings suggest that epoetin alfa may have
      potential therapeutic utility in patients with ischemic CNS injury.

PMID- 14582002
TI  - The evolution of warning signals as reliable indicators of prey defense.
AB  - It is widely argued that defended prey have tended to evolve conspicuous traits
      because predators more readily learn to avoid defended prey when they are
      conspicuous. However, a rival theory proposes that defended prey have evolved
      such characters because it allows them to be distinguished from undefended prey.
      Here we investigated how the attributes of defended (unprofitable) and undefended
      (profitable) computer-generated prey species tended to evolve when they were
      subject to selection by foraging humans. When cryptic forms of defended and
      undefended species were similar in appearance but their conspicuous forms were
      not, defended prey became conspicuous while undefended prey remained cryptic.
      Indeed, in all of our experiments, defended prey invariably evolved any trait
      that enabled them to be distinguished from undefended prey, even if such traits
      were cryptic. When conspicuous mutants of defended prey were extremely rare, they
      frequently overcame their initial disadvantage by chance. When Batesian mimicry
      of defended species was possible, defended prey evolved unique traits or
      characteristics that would make undefended prey vulnerable. Overall, our work
      supports the contention that warning signals are selected for their reliability
      as indicators of defense rather than to capitalize on any inherent educational
      biases of predators.

PMID- 14582003
TI  - Mapping functional similarity of predators on the basis of trait similarities.
AB  - Theoretical and empirical studies in community ecology often simplify their study
      system by lumping together species on the basis of trait similarities (e.g.,
      their taxonomy, resource or microhabitat usage) and then assume species sharing
      similar traits are functionally similar. To date, no study has directly tested
      whether species more similar with respect to any of these traits are more similar
      in their functional effects on population or ecosystem processes. In this study,
      we examined the association between traits and functional effects of six
      different aquatic predatory vertebrates. We demonstrated that functional
      similarity across multiple response variables was not correlated with trait
      similarity, but differences in trait values were associated with significantly
      different effects on individual response variables. The exact relationship
      between species traits and functional effect of predators, however, was different
      for each response variable. Using traits to predict functional similarity among
      species may be useful when considering individual response variables, but only if
      it is known which traits have the greatest influence on the response variable of
      interest. It is doubtful that any one scheme will predict the functional
      similarity of species across a diverse array of response variables because each
      response will likely be strongly influenced by different traits.

PMID- 14582004
TI  - Sexual selection favors female-biased sex ratios: the balance between the
      opposing forces of sex-ratio selection and sexual selection.
AB  - In a verbal model, Trivers and Willard proposed that, whenever there is sexual
      selection among males, natural selection should favor mothers that produce sons
      when in good condition but daughters when in poor condition. The predictions of
      this model have been the subject of recent debate. We present an explicit
      population genetic model for the evolution of a maternal-effect gene that biases
      offspring sex ratio. We show that, like local mate competition, sexual selection
      favors female-biased sex ratios whenever maternal condition affects the
      reproductive competitive ability of sons. However, Fisherian sex-ratio selection,
      which favors a balanced sex ratio, is an opposing force. We show that the
      evolution of maternal sex-ratio biasing by these opposing selection forces
      requires a positive covariance across environments between the sex-ratio bias
      toward sons (b) and the mating success of sons (r). This covariance alone is not
      a sufficient condition for the evolution of maternal sex-ratio biasing; it must
      be sufficiently positive to outweigh the opposing sex-ratio selection. To
      identify the necessary and sufficient conditions, we partition total evolutionary
      change into three components: (1) maternal sex-ratio bias, (2) sexual selection
      on sons, and (3) sex-ratio selection. Because the magnitude of the first
      component asymmetrically affects the strength of the second, biasing broods
      toward females in a poor environment evolves faster than the same degree of bias
      toward males in a good environment. Consequently, female-biased sex ratios,
      rather than male-biased sex ratios, are more likely to evolve. We discuss our
      findings in the context of the primary sex-ratio biases observed in strongly
      sexually selected species and indicate how this perspective can assist the
      experimental study of sex ratio evolution.

PMID- 14582005
TI  - Sex-biased dispersal and adaptation to marginal habitats.
AB  - If gene flow occurs through both sexes but only females contribute to population
      growth, adaptation to marginal (sink) habitats should be differentially affected
      by male versus female dispersal. Here I address this problem with two models.
      First, I consider the fate of a rare allele that improves fitness in the marginal
      habitat but reduces fitness in the core (source) habitat. Then I study the
      evolution of a polygenic character mediating a trade-off in fitness between the
      habitats. Both approaches led to qualitatively similar predictions. The effect of
      a difference in the dispersal rate between the sexes depends on the degree to
      which immigration from the core habitat boosts the reproductive output from the
      marginal habitat. This boost is slight if the marginal habitat is able to sustain
      well a population without immigration. In that case, both female- and male-biased
      dispersal is more favorable for adaptation to marginal habitats than equal
      dispersal of both sexes (assuming that the dispersal rate averaged over the sexes
      is kept constant). In contrast, if the marginal habitat is an absolute sink
      unable to sustain a population without immigration, the conditions for adaptation
      to that habitat are least favorable under highly male-biased dispersal and most
      favorable under highly female-biased dispersal. Under some circumstances, high
      average (male+female) dispersal is more favorable than low dispersal. Thus, gene
      flow should not be seen solely as thwarting adaptation to marginal habitats. The
      results are interpreted in terms of how male and female dispersal affects the
      relative rate of gene flow from the source to the sink habitat and in the
      opposite direction. This study predicts that ecological niches of taxa with
      female-biased dispersal should tend to be broader and more evolutionarily
      flexible.

PMID- 14582006
TI  - The evolution of dispersal under demographic stochasticity.
AB  - Temporal and spatial variations of the environment are important factors favoring
      the evolution of dispersal. With few exceptions, these variations have been
      considered to be exclusively fluctuations of habitat quality. However, since the
      presence of conspecifics forms part of an individual's environment, demographic
      stochasticity may be a component of this variability as well, in particular when
      local populations are small. To study this effect, we analyzed the evolution of
      juvenile dispersal in a metapopulation model in which habitat quality is constant
      in space and time but occupancy fluctuates because of demographic stochasticity.
      Our analysis extends previous studies in that it includes competition of
      resources and competition for space. Also, juvenile dispersal is not given by a
      fixed probability but is made conditional on the presence of free territories in
      a patch, whereas individuals born in full patches will always disperse. Using a
      combination of analytical and numerical approaches, we show that demographic
      stochasticity in itself may provide enough variability to favor dispersal even
      from patches that are not fully occupied. However, there is no simple
      relationship between the evolution of dispersal and various indicators of
      demographic stochasticity. Selected dispersal depends on all aspects of the life
      history profile, including kin selection.

PMID- 14582007
TI  - Toward a mechanistic understanding and prediction of biotic homogenization.
AB  - The widespread replacement of native species with cosmopolitan, nonnative species
      is homogenizing the global fauna and flora. While the empirical study of biotic
      homogenization is substantial and growing, theoretical aspects have yet to be
      explored. Consequently, the breadth of possible ecological mechanisms that can
      shape current and future patterns and rates of homogenization remain largely
      unknown. Here, we develop a conceptual model that describes 14 potential
      scenarios by which species invasions and/or extinctions can lead to various
      trajectories of biotic homogenization (increased community similarity) or
      differentiation (decreased community similarity); we then use a simulation
      approach to explore the model's predictions. We found changes in community
      similarity to vary with the type and number of nonnative and native species, the
      historical degree of similarity among the communities, and, to a lesser degree,
      the richness of the recipient communities. Homogenization is greatest when
      similar species invade communities, causing either no extinction or differential
      extinction of native species. The model predictions are consistent with current
      empirical data for fish, bird, and plant communities and therefore may represent
      the dominant mechanisms of contemporary homogenization. We present a unifying
      model illustrating how the balance between invading and extinct species dictates
      the outcome of biotic homogenization. We conclude by discussing a number of
      critical but largely unrecognized issues that bear on the empirical study of
      biotic homogenization, including the importance of spatial scale, temporal scale,
      and data resolution. We argue that the study of biotic homogenization needs to be
      placed in a more mechanistic and predictive framework in order for studies to
      provide adequate guidance in conservation efforts to maintain regional
      distinctness of the global biota.

PMID- 14582008
TI  - Fixed green and brown color morphs and a novel color-changing morph of the
      Pacific tree frog Hyla regilla.
AB  - Pacific tree frogs Hyla regilla are typically either green or brown in dorsal
      coloration. The frequency of green and brown individuals is known to fluctuate
      seasonally. Previous investigators have generally assumed that the green and
      brown body colors represent a "fixed" polymorphism and that seasonal changes in
      the proportion of the two body colors are a consequence of differential survival
      of the two color morphs. Here we report that, in addition to the "fixed" (i.e.,
      non-color-changing) green and brown morphs of H. regilla, there are some
      individuals that can change hue between green and brown. The distribution of
      color-change ability in our study population is bimodal, suggesting that "color
      changers" are a distinct morph rather than one extreme of a continuous
      distribution of color-change ability. Our findings suggest that background
      brightness, not hue, triggers color change in the newly discovered morph and that
      this change requires days to weeks to occur. Such slow color change is not well
      suited for making short-term changes in color as a frog moves between differently
      colored substrates. Rather, seasonal changes in habitat characteristics and/or
      microhabitat use are likely to maintain color-change ability. Color polymorphism
      and color-change ability appear to represent alternative responses to divergent
      selection for crypsis in a heterogeneous, seasonally variable environment.

PMID- 14582009
TI  - Delayed selfing and resource reallocations in relation to mate availability in
      the freshwater snail Physa acuta.
AB  - We study the influence of mate availability on the mating behavior of the self
      fertile, preferentially outcrossing freshwater snail Physa acuta. Previous
      optimization theory indicated that mating system interacts with life-history
      traits to influence the age at first reproduction, providing three testable
      predictions. First, isolated individuals should reproduce later than individuals
      with available mates in the expectancy of finding a partner and avoiding the cost
      of inbreeding. Second, resource reallocation to future fecundity is needed for
      such reproductive delays to evolve. Third, the reproductive delay can be
      optimized with respect to life-history traits (e.g., survival, growth) and the
      mating system (inbreeding depression). Our results largely validate these
      predictions. First, reproduction is significantly delayed in isolated individuals
      ("selfers") as compared with individuals frequently exposed to mates
      ("outcrossers"). Second, delayed reproduction is associated with reallocation to
      future growth, survival, and fecundity, although fecundity is also affected by
      the mating system (selfing vs. outcrossing). Third, the reproductive delay found
      (approximately 2 wk) is consistent with quantitative predictions from
      optimization models. The delay is largely heritable, which might be partly
      explained by among-family differences in the amount of inbreeding depression
      (mating system) but not growth or survival.

PMID- 14582010
TI  - The many growth rates and elasticities of populations in random environments.
AB  - Despite considerable interest in the dynamics of populations subject to
      temporally varying environments, alternate population growth rates and their
      sensitivities remain incompletely understood. For a Markovian environment, we
      compare and contrast the meanings of the stochastic growth rate (lambdaS), the
      growth rate of average population (lambdaM), the growth rate for average
      transition rates (lambdaA), and the growth rate of an aggregate represented by a
      megamatrix (shown here to equal lambdaM). We distinguish these growth rates by
      the averages that define them. We illustrate our results using data on an
      understory shrub in a hurricane-disturbed landscape, employing a range of
      hurricane frequencies. We demonstrate important differences among growth rates:
      lambdaS<lambdaM, but lambdaA can be < or > lambdaM. We show that stochastic
      elasticity, ESij, and megamatrix elasticity, EMij, describe a complex
      perturbation of both means and variances of rates by the same proportion.
      Megamatrix elasticities respond slightly and stochastic elasticities respond
      strongly to changing the frequency of disturbance in the habitat (in our example,
      the frequency of hurricanes). The elasticity EAij of lambdaA does not predict
      changes in the other elasticities. Because ES, although commonly utilized, is
      difficult to interpret, we introduce elasticities with a more direct
      interpretation: ESmu for perturbations of means and ESsigma for variances. We
      argue that a fundamental tool for studying selection pressures in varying
      environments is the response of growth rate to vital rates in all habitat states.

PMID- 14582011
TI  - The effects of the size and shape of landscape features on the formation of
      traveling waves in cyclic populations.
AB  - Recent field data indicate that in a number of cyclic populations, the cycles are
      organized spatially with the form of a periodic traveling wave. One way in which
      this type of wave is generated is when dispersing individuals encounter landscape
      features that impede movement in certain directions. In this article, we
      investigate the dependence of such periodic waves on ecological parameters and on
      the form of the landscape feature. Using a standard predator-prey model as a
      prototype for a cyclic population, we calculate the speed and amplitude of waves
      generated by a large landscape feature. This enables us to determine parameters
      for which the waves are stable; in other cases, they evolve into irregular
      oscillations. We then undertake for the first time a detailed study of the
      effects of the size and shape of a landscape feature on the waves that it
      generates. We show that size rather than shape is the key wave-forming property,
      with smaller obstacles generating waves with longer wavelength and waves from
      larger landscape features dominating those from smaller ones. Our results suggest
      that periodic traveling waves may be much more common than has previously been
      assumed in real ecological systems, and they enable quantitative predictions on
      the properties of these waves for particular cases.

PMID- 14582012
TI  - Diversity and stability in communities structured by asymmetric resource
      allocation.

PMID- 14582013
TI  - [Phenotypic variability of deletion 22q11.2. An analysis of 16 observations with
      special emphasis on the neurological manifestations].
AB  - INTRODUCTION: The microdeletion 22q11.2 affects 1/4000 live births and
      constitutes the most frequent interstitial chromosomal alteration in humans. It
      is involved in a heterogeneous series of phenotypic expressions. AIMS: To
      determine the most important clinical characteristics in a series of patients
      with this genetic molecular disorder. PATIENTS AND METHODS: We conducted a
      retrospective study of 16 patients who had been diagnosed, by means of FISH or
      PCR, as having microdeletion 22q11.2, and the following data were evaluated in a
      protocolised manner: sex, age, family background, characteristics of the
      pregnancy, birth, neonatal and post-neonatal periods, clinical and semiological
      data, as well as the results from the complementary explorations carried out
      according to the predominant pathology. RESULTS: The age at which the diagnosis
      was made oscillated between newly born and 8 years, with a predominance of males
      over females in a ratio of 3.2/1. In all, 81% of patients presented neurological
      disorders. Brain malformations were seen in six, hypoplasia of the anguli oris
      muscle in five, congenital facial palsy in three which was associated with brain
      malformations in one patient, retarded neurodevelopment in six cases and
      neurogenic arthrogryposis in one. Other findings such as congenital heart disease
      (75%), skeletal disorders (37%), peculiar phenotypes (31%), nephrourological
      disorders (19%) and hypoacusis (19%) constitute significant manifestations of the
      process. Some of the most noteworthy occasional events include retarded height
      and weight development, hypocalcemia and cleft palate. In one case involving a
      child whose mother suffered from chronic alcoholism, there were both phenotypic
      traits of this entity and of foetal alcohol syndrome at the same time. In four of
      the patients the FISH technique did not detect the deletion, which was confirmed
      by a technique involving DNA amplification with PCR. CONCLUSIONS: The presence of
      central and peripheral neurological alterations, together with cardiac, skeletal,
      renal and auditory disorders was confirmed, as was the existence of
      neurodevelopmental retardation and a peculiar phenotype. Both the frequency and
      the kind of disorder coincided with what has been described earlier. A number of
      facts stand out owing to their novelty. These include the high incidence of
      asymmetric crying facies, the existence of data compatible with foetal alcohol
      syndrome in one of the patients with this clinical entity, and the association
      with neurogenic arthrogryposis in another, which are circumstances that suggest
      the possibility of a causal relation with the deletion 22q11.2. Using DNA
      amplification with PCR is seen to be of greater diagnostic efficacy than the FISH
      technique.

PMID- 14582014
TI  - [Neuropsychological and behavioral profiles of children with attention
      deficit/hyperactivity disorder from cali, colombia].
AB  - INTRODUCTION: Several studies have found neuropsychological and behavioral
      disorders in children with attention deficit/hyperactivity disorder (ADHD), which
      have been explained as an executive dysfunction. OBJECTIVE: To describe and
      compare children with ADHD and a control group. PATIENTS AND METHODS: 79 seven to
      eleven-year-old children were selected and grouped according to ADHD DSM IV
      criteria and the T scores on a ADHD checklist. They were classified as
      predominantly inattentive (n=19), combined (n=24) and control (n=36) groups. Age,
      gender, socio economic status and intellectual quotient (>85) were statistically
      controlled. Neuropsychological functions were assessed with a child
      neuropsychological battery, and the behavioral dimensions were evaluated with the
      BASC's questionnaires, Conner's parents (CPRS) and teachers (CTRS) rating scales,
      and with a questionnaire for oppositional defiant (ODD) and conduct (CD)
      disorders. RESULTS: Statistically significant differences were found (P<0.01) in
      neuropsychological variables of mental control, continuous auditory performance,
      Rey's complex figure evocation and the Stroop's test. There were significant
      differences in the most BASC's internalizing and externalizing dimensions, so for
      the parents as for the teachers and self report questionnaire, and in the
      dimensions of CPRS, CTRS, ODD and CD questionnaires. CONCLUSION: Children with
      ADHD showed difficulties in sustained and selective attention, visual memory,
      inhibitory control, and they had behavioral disorders similar to those informed
      by previous studies.

PMID- 14582015
TI  - [Anomalies in brain haemodynamics in pre-eclamptic expectant mothers].
AB  - INTRODUCTION: Transcranial Doppler (TCD) is being used more and more frequently
      in the study of brain haemodynamics in pre-eclampsia/eclampsia. It has received
      less attention in the puerperium of these patients. AIMS: The aim of our study
      was to compare pre-eclamptic (PE) and normotensive (NT) patients at the end of
      gestation, using a Doppler velocimeter, and also to compare the results from PE
      women in two consecutive periods of time: at the end of gestation and in early
      puerperium (EP). PATIENTS AND METHODS: TCD was performed with bilateral
      evaluation of the anterior, middle and posterior cerebral arteries (ACA, MCA and
      PCA, respectively). Average speed (AS) and the pulsatility index (PI) were used
      as Doppler parameters. Arterial blood pressure (BP) and haematocrit were also
      measured. The AS, PI, average BP (ABP) and haematocrit were used as variables in
      the statistical analysis. At the end of gestation (33 weeks to full term) we
      compared the average values of these variables in PE (n=38) against those of NT
      (n=44). We also compared the results obtained for PE (n=30) in two consecutive
      periods: at the end of gestation and EP (the first five days following
      childbirth). RESULTS: At the end of gestation, AS were significantly higher in
      the PE than in the NT in all the arteries that were examined. The ABP was higher
      in the first group but there was no significant correlation between ABP and AS.
      PI were lower in the first group, with statistical signification in four of the
      six arteries. The AS rose significantly in the EP of the PE women, in spite of
      the existence of a drop in the ABP. Conversely, the PI remained unaltered.
      CONCLUSIONS: A pattern of high AS and low PI was found in PE women at the end of
      gestation and may be due to a primary failure of the brain's capacity to regulate
      itself. Anomalies in the TCD increased in the EP, despite a drop in the ABP, and
      this could account for the predominance of the neurological symptoms that are
      reported in the later forms of the syndrome.

PMID- 14582016
TI  - [Comparative study of bilateral lesions in the entorhinal cortex and in the
      fimbria fornix].
AB  - INTRODUCTION: Numerous reports show that lesions to hippocampus afferents, such
      as the entorhinal cortex (EC) and the fimbria fornix (FF), exert an effect on
      memory in rodents. There are, however, no long term comparative studies that show
      which of these lesions could be most useful as a model for studies into
      neuroplasticity. MATERIAL AND METHODS: Young male Sprague Dawley rats were used.
      Bilateral electrolytic lesion was caused to the EC or the FF was damaged by
      transection. One, four or 12 weeks later the animals were evaluated in a Morris
      water maze, first with an invisible platform and then with the platform within
      view. The results from the two groups were compared to each other and to those
      obtained from healthy controls and subjects with false lesions by means of a
      variance analysis. RESULTS: In the test with an invisible platform, both types of
      lesion gave rise to serious, irreparable involvement of the spatial memory of the
      animals, at least up to 12 weeks after the lesion. The test with the visible
      platform revealed significant differences between animals with lesion to the EC
      evaluated at 12 weeks, which suggests the development of some visual or motor
      deterioration in these animals. CONCLUSIONS: Although both lesions gave rise to
      behavioural deterioration that was irreversible in the long term in rodents, the
      lesion to the FF seems to be a better model for evaluating specific effects on
      learning and memory, since the lesion to the EC apparently triggers additional
      sensory and motor involvement.

PMID- 14582017
TI  - [Sialorrhea in patients with Parkinson. A six year prospective study].
AB  - INTRODUCTION: The sialorrhea has been recognised as one of the manifestations of
      Parkinson's disease, with a frequency of up to 80%. The evolution of patients
      with sialorrhea is unknown. PATIENTS AND METHODS: We study 26 male and 17 female
      patients with Parkinson's disease and sialorrhea. RESULTS: Evaluation at three
      years showed that sialorrhea had persisting in 18 of them, at six years showed
      that persisted in 8 patients. We found significant impairment in the sialorrhea
      group. CONCLUSION: If we accept the principle, that sialorrhea are levodopa
      resistant disorders as non nigrostriatal symptoms, secondary to a diffuser and
      more extended cerebral stem degeneration, we could assume that in these patients
      with sialorrhea cortical-sub cortical circuits are more widely involved leading
      to motor and cognitive impairment and depression.

PMID- 14582018
TI  - [Quality control of Doppler diagnoses in vascular neurology].
AB  - INTRODUCTION: The use of ultrasonography in the study of extracranial pathologies
      is becoming widespread among the different neurology services in our community.
      Its main limitation is that it is a technique that depends on the explorer. AIMS:
      The purpose of this study is to determine the reliability of our Neurosonology
      laboratory by validating its results. PATIENTS AND METHODS: We conducted a
      retrospective study by selecting the first 100 consecutive patients (with
      ischemic stroke) who had been examined in the year 2001 in the Neurosonology
      laboratory in our hospital. These subjects had to fulfil the requirement of
      having been submitted to both a Doppler study (carotid and transcranial) and a
      vascular neuroimaging study using magnetic resonance angiography (MRA) or
      panarteriography of the supra-aortic trunks (SAT) and of the brain by means of
      femoral puncture. RESULTS: In the study of the SAT the Doppler detected stenosis
      or occlusion with a sensitivity of 91.4% and a specificity of 92.3% and,
      therefore, a positive predictive value (PPV) of 86.4%. 75% of the occlusions were
      diagnosed with three false positives (which were in fact critical stenoses above
      95% instead of occlusion). As regards the evaluation of the transcranial Doppler
      (TCD), the sensitivity of the Doppler scan to detect stenoses above 50% is
      situated at 79%, with a PPV of 93%. For diffuse atheromatosis, however,
      sensitivity is 92.8%, and specificity is 93%. DISCUSSION: Findings agree with
      those offered by other studies conducted in our area using this technique, and
      show the reliability of this technique carried out in our Neurosonology
      laboratory. We therefore believe that Doppler echography of the SAT and TCD can
      be used for achieve an initial evaluation of cerebrovascular pathologies.

PMID- 14582019
TI  - [Usefulness of arteriography with multislice spiral computed tomography in the
      diagnosis of preocclusive stenosis of the cervical internal carotid artery].
AB  - INTRODUCTION: Distinction between near-occlusion and occlusion of the internal
      carotid artery (ICA) is relevant because patients can benefit from a surgical
      treatment in the first case. Digital subtraction angiography (DSA) is the best
      neuroimaging technique for its diagnosis but the possibility of related
      neurologic complications suggests the use of non-invasive tests. Ultrasound (US)
      and magnetic resonance angiography (MRA) have been proposed as alternative
      techniques of diagnosis. But these can provoke an erroneous diagnosis when a near
      occlusion of ICA is present. Multislice helicoidal computed tomographic
      angiography (MHCTA) can play a role in these situations. CASE REPORTS: Case 1:
      patient diagnosed of occlusion of the left ICA by cervical US. Cerebral magnetic
      resonance suggested severe stenosis of intracavernous ICA. MHTCA showed carotid
      permeability. Case 2: patient diagnosed by cervical US of near occlusion and of
      occlusion/pseudoocclusion by enhanced RMA. MHCTA showed filiform patency of the
      cervical ICA. Case 3: a cervical US diagnosed moderate stenosis of the right ICA
      and severe of the left. Transcranial Doppler suggested near occlusion of the
      right ICA. MHTCA confirmed near occlusion of the right ICA. CONCLUSION: MHCTA
      correctly diagnosed near occlusion in three patients in which minimally invasive
      techniques had discrepancies. MHTCA is a new diagnostic technique whose lack of
      dependence of flow makes a good alternative to confirm findings of US of the
      cervical ICA.

PMID- 14582020
TI  - [Guitarist's cramp: management with sensory re-education].
AB  - INTRODUCTION: Dystonia is defined as a sustained co-contraction of agonistic and
      antagonistic muscles that can cause twisting, twitching and abnormal postures.
      Occupational dystonias are included in a special group of pathologies that are
      secondary to a repeated effort related to the professional activity carried out
      by the sufferer, as can occur in guitarists, violinists and trumpet players, for
      example. Its pathophysiology includes descriptions of disorders affecting the
      peripheral and central nervous systems. Studies conducted in monkeys have shown
      that, through sensory stimulation, repeated movements can give rise to central
      anomalies in the somatosensory cortex, with growth of the receptive fields that
      are stimulated and deformation of the separations between those fields. CASE
      REPORT: We describe the case of a professional guitarist with a seven-year
      history of symptoms. A neurological examination revealed a co-contraction in the
      right hand that triggered the extension of the index and little fingers, which
      made it difficult for him to play his instrument. The patient was submitted to
      sensory re-education therapy with the use of a splint and a two-month routine of
      exercises. The response was evaluated using a subjective scale of the patient's
      symptoms and measurements of the maximum angles of flexion and extension of the
      affected fingers. Both methods reduced the patient's discomfort and allowed him
      to exhibit greater skill when playing the guitar. CONCLUSIONS: Occupational
      dystonias produced by repeated stimulation present alterations in the sensory
      region of the cortex, with the involvement of motor performance that improves
      with sensory re-education therapy.

PMID- 14582021
TI  - [Dilation of the ventriculus terminalis, an infrequent cause of lower back pain.
      Magnetic resonance findings].
AB  - INTRODUCTION: Ventriculus terminalis is the name given to a congenital disorder
      that consists in the appearance of a small oval ependymal cystic cavity in the
      conus medullaris. It is formed during embryogenesis as a result of the
      differentiation between the canalisation and regression of the spinal cord. The
      aim of this study is to describe the findings obtained by magnetic resonance (MR)
      imaging concerning the dilation of the ventriculus terminalis in a symptomatic
      patient. CASE REPORT: A 41-year-old female with a three-year history of lower
      back pain and irradiated pain in the left leg, together with paresthesias. The
      physical exploration revealed hypoesthesia with a low level of sensitivity in
      D12, L1 and L2. MR images revealed the presence of a cystic lesion located in the
      conus medullaris, with a well defined outline, and which was not enhanced
      following contrast IV. CONCLUSION: The ventriculus terminalis is the ependymal
      cavity that lies in the conus medullaris. It may present an abnormal dilation and
      we need to know of its existence, where it is typically located and its signal
      characteristics in MR in order to be able to diagnose and differentiate it from
      cystic tumours situated in the same place, which can display a similar appearance
      in MR images. The therapeutic management of these patients will depend on their
      clinical progress. MR scanning is fundamental for diagnosing and monitoring
      symptomatic patients.

PMID- 14582022
TI  - [Medical treatment of intracranial arterial stenosis. Are primary and secondary
      prevention the same thing?].
AB  - AIMS: In this study we review the risk factors associated with the formation and
      progression of an atheroma plaque, the mechanism involved in cerebral ischemia
      secondary to intracranial atheromatosis and possible medical treatment in primary
      and secondary prevention. DEVELOPMENT: Medical treatment of intracranial stenoses
      (ICS) is aimed at stopping the progression of the atheroma plaque and at
      preventing recurrences in the case of symptomatic stenoses. It is based on the
      control of vascular risk factors, the use of statins and antithrombotic therapy
      (antiplatelet or anticoagulation drugs). Although antiplatelet agents have not
      proved to be beneficial in the primary prevention of stroke, they are recommended
      in patients with ICS in order to lower the risk of heart attack associated with
      this pathology. The use of antiplatelet drugs in the secondary prevention of
      ischemic stroke secondary to an ICS is based on clinical trials which have shown
      that antiaggregation prevents non-cardioembolic strokes. Nevertheless, several
      retrospective studies have observed that oral anticoagulation is better than
      antiaggregation with aspirin. Two prospective clinical trials are currently being
      conducted which will, in the next few years, help to determine what the first
      choice medical treatment is for this group of patients. CONCLUSIONS: Medical
      treatment of ICS patients must include the control of vascular risk factors and
      the use of statins. New studies are needed to be able to establish the first
      choice antithrombotic drug in secondary prevention.

PMID- 14582023
TI  - [Involvement of the immunological system in the pathogenesis of transmissible
      spongiform encephalopathies].
AB  - OBJECTIVE: We review the current knowledge relative to the role of different
      immune system components and their contribution the spread of prions throughout
      the infected organism. DEVELOPMENT: During the last years research made on
      transmissible spongiform encephalopathies conducted to the assumption that
      changes in the structure of a determined protein (prion protein, PrP) may become
      self-propagative. The generally assumed finding of an abnormally folded protein
      as the causative agent, able to propagate in hosts different from it was
      originated, is changing our views of transmissible diseases. The concept of
      infection resulting from pathogen propagation within a susceptible host has been
      steadily linked to the ability of nucleic acids to replicate their own coded
      information. In the prionosis, term comprising all known prion disorders, the
      information seems to be coded within the own protein conformation. This
      phenomena, once again, challenges the well-established principles of molecular
      biology. CONCLUSIONS: Propagation of prions uses strategies not previously
      recognized, and depends upon prion conformation and/or specific host
      restrictions. Thus, certain sheep and goat prion strains (scrapie) or human
      (variant of Creutzfeldt-Jakob disease) invade the brain after an initial
      interaction with the immune system of affected individuals. The involvement of
      the lymphoreticular system or, at least, certain host's immune competence seems
      to be a prerequisite for neuro-invasion after a natural infection or peripheral
      inoculation. On the other hand, proper identification of immune cell types
      involved may open the possibility for post exposure prophylaxis.

PMID- 14582024
TI  - [Some considerations about the possible pathological mechanisms at work in
      antiphospholipid syndrome and stroke].
AB  - INTRODUCTION AND DEVELOPMENT: Over the last two decades antiphospholipid syndrome
      (APS) has started to be recognized from the association of apparently anionic
      phospholipid-specific antibodies with thrombosis, thrombocytopenia and recurrent
      foetal losses. This syndrome affects patients with systemic lupus erythematosus
      and is considered to be an important cause of thromboembolic disease.
      Antiphospholipid antibodies are serum immunoglobulins that react with negatively
      charged phospholipids, albeit directly or by means of a cofactor, affect the
      coagulation system, and promote thrombosis. Recent research has been directed
      towards gaining an understanding of the mechanisms by which these antibodies are
      able to play a direct role in the pathophysiology of thrombosis, and the extent
      to which certain risk factors, such as smoking, high blood pressure, lipid
      disorders and so on, exert an influence over the expression of phospholipids in
      the cerebral endothelium. CONCLUSION: These antibodies have no single mechanism
      of action; different authors have described different pathological mechanisms,
      which help us to understand the heterogeneous clinical manifestations of APS.

PMID- 14582025
TI  - [Diabetic neuropathy: vascular disease?].
AB  - INTRODUCTION: The major neurologic complications of diabetes are: 1) Neuropathy,
      both peripheral and autonomic, with principal manifestations in the lower limbs;
      2) Microvascular disease, mainly affecting the retina, resulting in blindness;
      and 3) Macrovascular disease, presenting with atherosclerosis in the cerebral
      arteries causing ischemic cerebrovascular disease and stroke. METHOD: The
      definition of diabetic neuropathy has changed over the last 50 years. Over the
      last 20 years there have been three main pathogenetic theories to explain
      diabetic neuropathy: the polyol pathway theory, the microvascular theory, and the
      glycosylation end product theory. It is apparent that several pathophysiologic
      factors probably operate simultaneously, and it may be too simplistic to attempt
      to explain the many clinical and pathologic findings of diabetic neuropathy
      through a single theory. Diabetic peripheral neuropathy is not caused by large
      vessel peripheral vascular disease, however, it does appear that small vessel
      disease plays a role. CONCLUSION: It seems likely, that microangiopathy on the
      one hand and changes of various metabolic pathways due to hyperglycemia on the
      other hand are much more related to each other than it was suggested previously.

PMID- 14582027
TI  - [Abstracts of the 2nd International Congress of Neuropsychology on the Internet.
      1-31 May 2003].

PMID- 14582026
TI  - [Treatment in spontaneous intracerebral haemorrhage. Analysis of Spanish clinical
      series].
AB  - OBJECTIVE: In the spontaneous intracerebral hemorrhage (SICH) there are a small
      number of unequivocally indicators of surgical or conservative treatment.
      DEVELOPMENT: An extensive bibliographic revision of studies of patients with
      spontaneous ICH admitted to Spanish Hospitals has been completed. Later on,
      studies related to analyses and results of mortality and functional state of
      surgical and conservative treatments of ICH were gathered. Using the Cochrane
      Collaboration Manual the methodological quality of the studies has been
      evaluated. CONCLUSIONS: The chosen studies were 25 clinical series. Only two
      studies comparing the surgical against the conservative treatment of
      supratentorial ICH has been found. The intrinsic methodological quality
      associated to this type of studies does not allow to establish valid conclusions
      on the efficacy of one treatment over another. Nonetheless it has utility
      considering that it reveals the chosen treatment and the outcomes in the
      published studies. We did not found studies evaluating the efficacy of both
      treatments in Spain with a prospective randomised design, with an adequate size,
      analysing mortality, dependency and quality of life of the affected patients.
      Therefore, our final conclusion is that given the importance of the information
      that could be extracted from these studies in order to design the more efficient
      treatment of ICH no delay to complete them can be admitted.

PMID- 14582028
TI  - [Spontaneous intracranial hypotension: atypical findings in magnetic resonance
      imaging].

PMID- 14582029
TI  - [Hemochromatosis: iron deposits in the globi pallidi].

PMID- 14582030
TI  - Stable patients with atherosclerotic renal artery stenosis should be treated
      first with medical management.

PMID- 14582031
TI  - Stable patients with atherosclerotic renal artery stenosis should be treated
      first with medical management.

PMID- 14582032
TI  - Malnutrition-inflammation complex syndrome in dialysis patients: causes and
      consequences.
AB  - Protein-energy malnutrition (PEM) and inflammation are common and usually
      concurrent in maintenance dialysis patients. Many factors that appear to lead to
      these 2 conditions overlap, as do assessment tools and such criteria for
      detecting them as hypoalbuminemia. Both these conditions are related to poor
      dialysis outcome. Low appetite and a hypercatabolic state are among common
      features. PEM in dialysis patients has been suggested to be secondary to
      inflammation; however, the evidence is not conclusive, and an equicausal status
      or even opposite causal direction is possible. Hence, malnutrition-inflammation
      complex syndrome (MICS) is an appropriate term. Possible causes of MICS include
      comorbid illnesses, oxidative and carbonyl stress, nutrient loss through
      dialysis, anorexia and low nutrient intake, uremic toxins, decreased clearance of
      inflammatory cytokines, volume overload, and dialysis-related factors. MICS is
      believed to be the main cause of erythropoietin hyporesponsiveness, high rate of
      cardiovascular atherosclerotic disease, decreased quality of life, and increased
      mortality and hospitalization in dialysis patients. Because MICS leads to a low
      body mass index, hypocholesterolemia, hypocreatininemia, and hypohomocysteinemia,
      a "reverse epidemiology" of cardiovascular risks can occur in dialysis patients.
      Therefore, obesity, hypercholesterolemia, and increased blood levels of
      creatinine and homocysteine appear to be protective and paradoxically associated
      with a better outcome. There is no consensus about how to determine the degree of
      severity of MICS or how to manage it. Several diagnostic tools and treatment
      modalities are discussed. Successful management of MICS may ameliorate the
      cardiovascular epidemic and poor outcome in dialysis patients. Clinical trials
      focusing on MICS and its possible causes and consequences are urgently required
      to improve poor clinical outcome in dialysis patients.

PMID- 14582033
TI  - Allocation of deceased donor kidneys: past, present, and future.
AB  - The manner in which deceased donor kidneys are allocated has broad relevance to
      the care of patients with end-stage renal disease. An algorithm governing the
      allocation of deceased donor kidneys has been applied in the United States since
      1987. Adjustments were made to facilitate the national sharing of highly matched
      kidneys, but the main components of the algorithm remained largely unchanged. In
      ensuing years, the number of patients on the waiting list has increased steadily
      while the supply of kidneys has remained constant. The waiting time for an organ
      now is measured in years, and the allocation of organs has become unpredictable.
      As of October 2002, several important changes have been made to the algorithm.
      These changes are designed to increase the relative number of minority patients
      who undergo transplantation and the use of extended-criteria donor kidneys. They
      also have practical implications for the management of patients on the waiting
      list. The rationale behind these changes is discussed in the context of the
      ethical underpinnings of kidney allocation.

PMID- 14582034
TI  - Stem-cell therapy for renal diseases.
AB  - Significant attention is currently directed to the biological and therapeutic
      capabilities of stem cells for developing novel treatments for acute and chronic
      kidney diseases. To date, viable sources of stem cells for renal therapies
      include adult bone marrow and embryonic tissues, including the metanephric
      mesenchyme and mesonephros. Native adult kidney stem cells have yet to be
      identified. Systemically introduced stem cells can engraft in sites of renal
      disease and injury to show donor phenotypes. Stem cells can differentiate into
      cells similar to glomeruli, mesangium, and tubules in the kidneys. The impact of
      stem-cell engraftment and differentiation on renal function presently is unknown.
      Identification of renal diseases treatable with stem-cell therapies is expected
      to evolve as stem-cell technologies advance. Methods of modifying stem cells to
      improve homing, differentiation, and integration into host tissues need further
      characterization. Ethical and legal controversies about embryonic research and
      cloning are shaping the regulation and funding of stem-cell research for kidney
      diseases. Scientific and clinical understanding of stem cells and their potential
      for renal treatments are in the early stage of development. This field offers
      great promise, and there are significant opportunities for future investigation
      in clinical, biological, and ethical aspects of stem-cell therapy for kidney
      diseases.

PMID- 14582035
TI  - Hepatic drug metabolism and transport in patients with kidney disease.
AB  - The disposition of many drugs is altered in patients with acute (AKD) and chronic
      kidney disease (CKD). A decline in renal clearance of several drugs has been
      correlated significantly with residual renal function (ie, creatinine clearance)
      of subjects. Reductions in nonrenal clearance of some compounds also have been
      reported and associated with clearance of markers of oxidative and/or conjugative
      metabolism or P-glycoprotein-mediated transport. Although initial accounts of
      reduced hepatic microsomal cytochrome P-450 (CYP) content and activity in animal
      models of AKD and CKD were published almost 25 years ago, it is only in the last
      decade that technical advances in molecular biology and clinical pharmacology
      have enabled researchers to begin to characterize the phenotypic expression of
      individual enzymes and, importantly, distinguish the molecular and/or genetic
      basis for these changes. The selective modulation of hepatic CYP enzyme activity
      observed in kidney disease is caused, at least in part, by differentially altered
      expression of several CYP isoforms. This review summarizes data available through
      June 2003 regarding the effect of AKD and CKD on drug metabolism. Knowledge of
      the impact and nature of these alterations associated with kidney disease may
      facilitate the individualization of medication management in this patient
      population.

PMID- 14582036
TI  - Renal insufficiency as a predictor of adverse events and mortality after renal
      artery stent placement.
AB  - BACKGROUND: Renal artery stenosis (RAS) is associated with substantial morbidity
      and mortality. This relationship is strongest in the presence of renal
      insufficiency (RI). The goal of this study is to assess the relationship between
      RI, mortality, and adverse events in the setting of renovascular disease.
      METHODS: Two hundred sixty-one patients with significant RAS treated with
      endovascular stenting were followed up prospectively for 21 +/- 18 months (range,
      0 to 85 months). Blood pressure (BP), renal function, medication use, and
      comorbidities were assessed. Death was verified through the Social Security Death
      Master Index File, and cause of death was derived from death certificates.
      Medical records of 230 subjects subsequently were reviewed to identify adverse
      cardiovascular and renal events. RESULTS: Overall, 37% of patients experienced at
      least 1 adverse event postprocedure. Myocardial infarction (MI) and congestive
      heart failure (CHF) events increased with degree of baseline RI. Seventy-three
      deaths (28%) occurred postprocedure (range, 13 to 2,457 days). Baseline
      characteristics associated with mortality included advanced age, decreased use of
      beta-blockers, increased use of diuretics, increased serum creatinine (Cr) level,
      decreased Cr clearance (CrCl), bilateral stenoses or stenosis of a solitary
      kidney, history of CHF, and history of MI. Follow-up characteristics associated
      with mortality included lower systolic and diastolic BP, increased serum Cr
      level, and decreased CrCl. RI at baseline and follow-up remained associated with
      mortality after adjusting for other clinically and statistically significant
      variables. Patients in whom renal function improved after stenting appeared to
      show improved survival over those without improved renal function (45% versus 0%
      cumulative survival, P < 0.05). CONCLUSION: In patients with RAS undergoing stent
      therapy, baseline RI is associated with an increased incidence of adverse events,
      as well as decreased survival, independent of other baseline clinical factors.
      Importantly, improvement in renal function appears to be associated with
      increased survival.

PMID- 14582037
TI  - Progression of renal insufficiency in type 2 diabetes with and without
      microalbuminuria: results of the Heart Outcomes and Prevention Evaluation (HOPE)
      randomized study.
AB  - BACKGROUND: In patients with type 2 diabetes with overt nephropathy, the risk for
      progressive renal failure is high. This risk is less well established for those
      with type 2 diabetes and microalbuminuria or normalbuminuria. We studied changes
      in serum creatinine levels during 3.5 to 5.5 years in a large cohort of people
      with diabetes at high cardiovascular risk with microalbuminuria or
      normalbuminuria. METHODS: Retrospective analysis of serum creatinine levels at
      baseline and yearly thereafter was performed in the Microalbuminuria and Renal
      Outcomes in the Heart Outcomes and Prevention Evaluation study comparing
      ramipril's effects with placebo during 4.5 years in 3,577 participants with
      diabetes, including 1,139 participants with microalbuminuria and 333 participants
      with renal insufficiency. Participants with dipstick-positive proteinuria (>1+)
      or serum creatinine levels greater than 2.3 mg/dL (200 micromol/L) were excluded.
      RESULTS: Serum creatinine levels did not increase significantly during the study
      if all participants with diabetes are considered or for subgroups with
      microalbuminuria and/or renal insufficiency at baseline. However, slopes of serum
      creatinine over time showed a significant trend for increasing values. There were
      no differences between the placebo and ramipril-treated groups. A serum
      creatinine level of 1.4 mg/dL (125 micromol/L) or greater newly developed in 474
      of 3,238 people (243 patients, placebo; 231 patients, ramipril; P = 0.5033). A
      doubling of baseline serum creatinine level or end-stage renal disease developed
      in 8 of 333 participants with renal insufficiency at baseline. CONCLUSION: In
      people with type 2 diabetes, but without overt nephropathy, who are at high risk
      for cardiovascular disease, progression of renal insufficiency is slow on the
      basis of changes in creatinine levels. On the basis of reaching threshold levels
      of renal function, progression rates are clinically meaningful, especially
      considering population life expectancy.

PMID- 14582038
TI  - C-106T polymorphism of AKR1B1 is associated with diabetic nephropathy and
      erythrocyte aldose reductase content in Japanese subjects with type 2 diabetes
      mellitus.
AB  - BACKGROUND: The C-106T polymorphism of AKR1B1, which encodes aldose reductase
      (AR), was reported to be associated with diabetic nephropathy (DN). However, this
      association in Japanese patients with type 2 diabetes mellitus and its potential
      role as a clinical marker remain unclear. METHODS: The C-106T polymorphism was
      genotyped in 228 cases (microalbuminuria or overt proteinuria) and 220 controls
      (normoalbuminuria with diabetes duration > or =10 years) for a case-control
      comparison, and the association with erythrocyte AR content was investigated. In
      addition, a new C-11G polymorphism in the promoter region of AKR1B1 was
      genotyped. RESULTS: The distribution of genotypes of the C-106T polymorphism in
      cases was significantly different from that in controls (P = 0.031). Carriers of
      the TT genotype at the C-106T polymorphism were more frequent in cases than
      controls, with an odds ratio of 4.7 (95% confidence interval, 1.3 to 17).
      Erythrocyte AR content was significantly elevated in TT carriers in comparison to
      non-TT carriers (13.1 +/- 1.2 versus 10.2 +/- 1.2 ng/mg hemoglobin [Hb]; P <
      0.001) and in cases in comparison to controls (10.6 +/- 1.3 versus 10.1 +/- 1.2
      ng/mg Hb; P = 0.041). However, distribution of genotypes of the C-11G
      polymorphism and estimated frequencies of haplotypes defined by these 2
      polymorphisms did not differ between cases and controls. CONCLUSION: The TT
      genotype of the C-106T polymorphism of AKR1B1 increases the risk for DN in
      Japanese subjects with type 2 diabetes mellitus, which could be linked in part to
      greater expression of AR.

PMID- 14582039
TI  - Autosomal recessive Alport's syndrome and benign familial hematuria are collagen
      type IV diseases.
AB  - BACKGROUND: Alport's syndrome (AS) is a genetically heterogeneous renal
      hereditary disease. Mutations in collagen type IV genes have been described to be
      responsible for X-linked (COL4A5), autosomal recessive, and autosomal dominant AS
      (COL4A3/COL4A4). Moreover, at least 40% of benign familial hematuria (BFH) cases
      cosegregate with the COL4A3/COL4A4 loci, following a dominant pattern of
      inheritance. Therefore, it has been suggested that BFH may represent the carrier
      state for autosomal recessive AS. METHODS: We report a mutational study of the
      COL4A3 and COL4A4 genes in 14 AS and 2 BFH families. When possible, linkage
      analysis has been performed to confirm the pattern of inheritance. One affected
      proband from each family underwent mutation screening by single-strand
      conformation polymorphism/heteroduplex analysis. RESULTS: We identified 13
      mutations within the COL4A3 gene and 2 mutations within the COL4A4 gene, 9 of
      which are first reported here. We also detected 14 polymorphisms within the
      COL4A3 gene and 15 polymorphisms within the COL4A4 gene, 7 of them not previously
      described. In 2 of our AS families, we found mutations previously reported for
      BFH, and we characterized a novel mutation shared by an AS and a BFH family.
      CONCLUSION: Collagen type IV nephropathy is an entity in itself, and phenotypic
      manifestations of COL4A3/COL4A4 mutations may range from monosymptomatic
      hematuria (BFH) to severe renal failure (AS), depending on the gene dosage. In 3
      of our families, we genetically confirmed that BFH represents the carrier state
      for autosomal recessive AS.

PMID- 14582040
TI  - Lymphomas diagnosed by percutaneous kidney biopsy.
AB  - BACKGROUND: Occult renal lymphoma clinically mimicking renal medical disease
      constitutes a diagnostic challenge to nephrologists, radiologists, and renal
      pathologists. The clinical and radiological findings, mostly nonspecific or
      inconclusive, seldom obviate the need for a kidney biopsy. METHODS AND RESULTS:
      We report 5 new cases of diffuse bilateral renal lymphoma diagnosed by
      percutaneous kidney biopsy, all presenting with acute renal failure (ARF) of
      unknown cause. Three cases showed an interstitial and 2 an
      intraglomerular/intravascular type of lymphomatous infiltration. All tumors were
      of B-cell lineage. Our cases add to 50 similar cases reported since 1980.
      Considering all 55 cases together, 39 (87%) of the 44 cases with interstitial and
      5 of 11 (45%) of those with intraglomerular lymphoma presented with ARF. In
      contrast, 5 of 10 cases with intraglomerular but none with interstitial
      infiltration presented with nephrotic range proteinuria. All but 2 cases (95%)
      with ARF and interstitial lymphoma but none with ARF and intraglomerular lymphoma
      showed bilaterally enlarged kidneys. Signs of extrarenal lymphomatous involvement
      were detected in 24 cases (44%) at the time of kidney biopsy or shortly
      thereafter. However, in only 10 cases (18%), all with interstitial lymphoma, was
      a tumor suspected prior to biopsy, mainly based on radiographical evidence of
      enlarged kidneys. CONCLUSION: Both types of diffuse bilateral renal lymphoma may
      clinically mimic renal medical disease. ARF in interstitial and in
      intraglomerular lymphoma may be due to increased intrarenal pressure and
      intraglomerular obstruction, respectively. Percutaneous kidney biopsy provides
      the most expedient means of establishing the diagnosis. Differential diagnosis
      includes interstitial nephritis and proliferative glomerulonephritis.

PMID- 14582042
TI  - Cardiovascular and thromboembolic events following hypertensive pregnancy.
AB  - BACKGROUND: Hypertension is a common complication of pregnancy. Previous evidence
      has linked pregnancy-related hypertension to maternal cardiovascular disease. We
      conducted a population-based cohort study to estimate the risks for
      cardiovascular and thromboembolic events in women with pregnancy-related
      hypertension. METHODS: We analyzed data from all singleton births recorded in
      Washington State from 1987 to 1998. Mothers were classified as having gestational
      hypertension, preeclampsia, or chronic hypertension based on hospital discharge
      and birth record information. Birth records were linked to subsequent
      hospitalizations within Washington State. Proportional hazards models were used
      to estimate the relationship between each form of pregnancy-related hypertension
      and subsequent risk for cardiovascular and thromboembolic events. RESULTS: We
      identified 31,239 eligible hypertensive pregnancies from 807,010 births. During
      follow-up, there were 118 hospitalizations for a first acute cardiovascular event
      and 172 hospitalizations for a first thromboembolic event. Gestational
      hypertension, mild preeclampsia, and severe preeclampsia were associated with 2.8
      fold (95% confidence interval [CI], 1.6 to 4.8), 2.2-fold (95% CI, 1.3 to 3.6),
      and 3.3-fold (95% CI, 1.7 to 6.5) greater risks for cardiovascular events,
      respectively. Severe preeclampsia was associated with a 2.3-fold (95% CI, 1.3 to
      4.2) greater risk for thromboembolic events. CONCLUSION: Preeclampsia and
      gestational hypertension are associated with increased risk for cardiovascular
      events. Pregnancy-induced hypertension appears to be an important risk factor for
      the development of future cardiovascular disease in young women.

PMID- 14582041
TI  - Hospitalization during advancing chronic kidney disease.
AB  - BACKGROUND: The care of patients with end-stage renal disease (ESRD) is
      associated with substantial costs to society, much of which is accounted for by a
      high rate of hospitalization. However, the influence of declining kidney function
      on hospitalization as ESRD approaches is not well understood. METHODS: We
      performed a retrospective cohort study of national data to evaluate the frequency
      of hospitalizations among patients with chronic kidney disease (CKD) who reached
      ESRD and had at least 2 years of Medicare eligibility before initiation of
      dialysis therapy. The study period for each patient extended from 2 years before
      to 6 months after the initiation of dialysis therapy. RESULTS: The study cohort
      was composed of 109,321 patients with a mean age of 75 years, all of whom
      initiated long-term dialysis therapy between 1995 and 1998. Mean hospitalization
      rate was 134 hospitalizations/1,000 patient-months at risk (PMAR).
      Hospitalization rates gradually increased as ESRD approached, peaking in the 3
      months immediately after the initiation of dialysis therapy at 487
      hospitalizations/1,000 PMAR. Cause-specific hospitalization rates mirrored this
      trend and were greatest for placement of vascular access and diagnoses related to
      cardiovascular (CVD) and infectious disease. CONCLUSION: Hospitalizations during
      CKD become more frequent with the approach of ESRD. The majority of these
      hospitalizations, both before and after the initiation of dialysis therapy, are
      caused by comorbidity related to CKD. These hospitalizations may be favorably
      impacted on by heightened attention to the prevention and management of CVD and
      timely placement of vascular access during CKD.

PMID- 14582043
TI  - The extracellular fluid-to-intracellular fluid volume ratio is associated with
      large-artery structure and function in hemodialysis patients.
AB  - BACKGROUND: Large-artery derangement is a major risk factor for cardiovascular
      and all-cause mortality in patients with end-stage renal disease (ESRD). It is
      not clear how body fluid distribution affects large-artery structure and function
      in patients with ESRD. METHODS: One hundred fifty-seven hemodialysis (HD)
      patients (mean age, 55.9 +/- 15.1 years; 76 men, 81 women) were enrolled.
      Influence of the extracellular fluid (ECF)-to-intracellular fluid (ICF) ratio
      derived from bioimpedance spectroscopy on the structure and function of the
      common carotid artery (CCA) and aorta was analyzed. One hundred forty-four
      healthy subjects were examined to obtain normal reference values for body fluid
      compartments. Based on ECF-ICF ratio, 2 groups were identified: ECF-ICF ratio in
      the 95th percentile or less and ECF-ICF ratio greater than the 95th percentile of
      age- and sex-stratified normal reference values. RESULTS: ECF-ICF ratio was
      significantly related to CCA diameter (r2 = 0.26; P < 0.001), CCA incremental
      modulus (E(inc); r2 = 0.15; P < 0.001), carotid augmentation index (AGI; r2 =
      0.10; P < 0.001), and aortic pulse wave velocity (aPWV; r2 = 0.21; P < 0.001).
      ECF-ICF ratio remained a significant independent determinant for CCA diameter
      (model r2 = 0.47; P < 0.001), E(inc) (r2 = 0.29; P < 0.001), aPWV (r2 = 0.51; P <
      0.001), and AGI (r2 = 0.40; P < 0.001) when age, sex, mean blood pressure,
      anthropometrical parameters, HD duration, and status of diabetes mellitus were
      accounted for. HD patients with an ECF-ICF ratio greater than the 95th percentile
      had a greater CCA diameter, E(inc), aPWV, and AGI than their counterparts.
      CONCLUSION: ECF-ICF ratio is associated with large-artery structure and function
      in HD patients. Patients with ESRD with a high ECF-ICF ratio are characterized by
      significant large-artery derangement.

PMID- 14582044
TI  - Predictors of successful arteriovenous fistula maturation.
AB  - BACKGROUND: Understanding the factors associated with successful arteriovenous
      fistula (AVF) maturation may provide an opportunity to improve vascular access
      outcomes. METHODS: This prospective cohort study enrolled 348 hemodialysis
      patients receiving an AVF and followed them until ascertainment of successful AVF
      maturation. Multivariable logistic regression was used to develop (1) explanatory
      models of factors associated with AVF success and (2) models for predicting
      success based on sociodemographic and comorbidity profiles. Receiver operating
      characteristic (ROC) curve analysis was performed to evaluate the discriminative
      ability of our predictive model. Predictive probabilities of AVF maturation under
      the assumption of optimal surgical technique defined by explanatory models were
      calculated. RESULTS: A total of 55.5% of AVFs successfully matured. A history of
      stroke or transient ischemic attack, increasing age, and dependence on dialysis
      at the time of access placement were associated with lower probabilities of
      maturation. Of potentially modifiable variables, maturation was associated with
      greater intraoperative doses of heparin, use of large-diameter veins, and mean
      arterial pressure of 85 mm Hg or greater. Using optimal surgical technique, the
      probability of successful AVF maturation would have been as high as 84%. A
      predictive logistic regression model had moderate ability to predict AVF
      maturation under optimal surgical therapy with an area under the ROC curve of
      0.69. CONCLUSION: Surgical technique potentially may be modified to yield a
      greater probability of successful AVF maturation. Predictive probabilities of
      successful AVF maturation under optimal surgical technique reinforce the view
      that functioning AVFs can be achieved in a large proportion of hemodialysis
      patients, consistent with experience in selected regions of the United States and
      abroad.

PMID- 14582045
TI  - The association of initial hemodialysis access type with mortality outcomes in
      elderly Medicare ESRD patients.
AB  - BACKGROUND: Dialysis access is critical for therapy delivery. Few studies have
      linked type of dialysis access to patient survival in the elderly population.
      METHODS: We included 1995 to 1997 incidence Medicare hemodialysis patients (N =
      66,595) who were 67 years and older at dialysis therapy initiation. Medicare
      Physician/Supplier claims were used to determine initial access type: simple
      fistula, autologous vein graft, synthetic graft, and hemodialysis catheter. We
      used International Classification of Diseases, Ninth Revision, Clinical
      Modification, codes to determine vascular access placement for renal failure. A
      Cox regression analysis assessed risk for death within 1 year, with explanatory
      variables of incidence year, age, sex, race, diabetes, initial access type, body
      mass index, days from first access placement date to initial dialysis date, and
      serum albumin, creatinine, and blood urea nitrogen levels. RESULTS: One-year
      crude death rates were 24.9%, 27.2%, 28.1%, and 41.5% for patients with simple
      fistulae, autologous vein grafts, synthetic grafts, and hemodialysis catheters,
      respectively. Patients with simple fistulae (the reference) had the lowest (P <
      0.0001) likelihood of death compared with those with synthetic grafts (hazard
      ratio [HR], 1.160; 95% confidence interval [CI], 1.084 to 1.241) or catheters
      (HR, 1.696; 95% CI, 1.593 to 1.806). No difference (P > 0.09) in mortality risk
      was detected between simple fistulae and autologous vein grafts or between
      autologous vein grafts and synthetic grafts. CONCLUSION: In the US Medicare
      dialysis population, type of initial hemodialysis access was associated with 1
      year mortality. Mortality risks were (in ascending order) fistulae, grafts, and
      catheters.

PMID- 14582046
TI  - Long-term study of high-comorbidity ESRD patients converted from conventional to
      short daily hemodialysis.
AB  - BACKGROUND: Conventional hemodialysis (CHD) is associated with suboptimal
      clinical outcomes and high mortality rates. Daily hemodialysis (DHD) has been
      reported to improve outcomes and quality of life (QOL), predominantly in self
      care or home dialysis populations. The effect of short DHD (sDHD) on patients
      with end-stage renal disease (ESRD) with high comorbidities has not been
      established. METHODS: This prospective study compared clinical outcomes and QOL
      in high-comorbidity patients with ESRD converted from CHD to sDHD while
      maintaining the same total weekly dialysis time. Study patients had 4.0 +/- 1.7
      major comorbid conditions in addition to ESRD. Standard dialysis parameters,
      antihypertensive and erythropoietin (EPO) requirements, Kidney Disease Quality of
      Life (KDQOL) measurements, vascular access problems, and hospitalization rates
      were compared while on sDHD therapy versus the previous 12 months on CHD therapy.
      RESULTS: Forty-two patients were studied on sDHD therapy for 793 patient-months
      during a 72-month period. During sDHD, standard Kt/V increased 31%,
      hospitalization days decreased significantly by 34%, and vascular access problems
      did not increase. Cumulative survival was 33% at 6 years. In the 20 patients who
      remained on sDHD therapy for 12 months, after 1 year, we found significant
      improvements in KDQOL scores, a 69% reduction in antihypertensive medications
      with stable blood pressure, and a 45% reduction in EPO requirements with stable
      hematocrits. We hypothesize that these improvements are the result of the less
      extreme solute and fluid fluctuations and greater dialysis dose provided by sDHD,
      even when weekly dialysis time is unchanged. CONCLUSION: High-comorbidity
      patients with ESRD converted to sDHD therapy had significantly improved clinical
      outcomes and QOL and decreased hospitalizations, with no increase in vascular
      access problems.

PMID- 14582047
TI  - Serum leptin in dialysis renal osteodystrophy.
AB  - BACKGROUND: The hormone leptin is considered to have a role in the prevention of
      osteoporosis and probably acts on bone tissue through inhibition of osteoclasia.
      Its action has been attributed to interference in osteoprotegerin (OPG)/OPG
      ligand equilibrium. Contradictory data also have been reported, casting doubts on
      the positive effect on bone mass of the hormone, at least in males. To date, the
      relation between serum leptin levels of dialysis patients and renal
      osteodystrophy, defined by histomorphometric and histodynamic parameters of bone,
      has not been studied. METHODS: The study included 46 hemodialysis patients (32
      men, 14 women; age, 57.2 +/- 11.4 years). A transiliac bone biopsy after double
      tetracycline labeling was performed for histological, histomorphometric, and
      histodynamic studies. Blood samples were drawn for leptin, intact parathyroid
      hormone (PTH), whole PTH (PTH1-84), OPG, bone alkaline phosphatase, calcium,
      phosphate, 25-hydroxycholecalciferol, and calcitriol. Serum leptin was measured
      by means of a radioimmunoassay. RESULTS: Eighteen patients had mixed
      osteodystrophy (MO); 17 patients, hyperparathyroidism; 9 patients, adynamic bone
      disease (ABD); and 2 patients, osteomalacia. Aluminum histochemistry results were
      positive in 1 patient with ABD and 1 patient with MO. A sex difference was found
      in serum leptin levels (48.9 +/- 38 ng/mL in women and 12.2 +/- 13.2 ng/mL in
      men; P < 0.0002). In the entire population, lnleptin correlated significantly
      with body mass index (BMI; P < 0.01). SD score (SDS) leptin (adjusted for BMI,
      sex, and age) correlated inversely with PTH1-84 level and osteoclastic surface
      (OcS/BS; P < 0.05) and had a borderline correlation with bone formation rate.
      Correlations between leptin levels and other parameters were enhanced in men. SDS
      leptin correlated inversely with OcS/BS (P < 0.01), osteoclastic number (P <
      0.01), and mineral apposition rate (P < 0.01). In addition, SDS leptin had a
      borderline inverse correlation with osteoblast surface (P < 0.06) and significant
      correlation with OPG level (P < 0.05). No difference was found in serum leptin
      levels between histological groups. CONCLUSION: The reported data confirm the
      finding of a positive relation between serum leptin level and BMI and greater
      levels in women compared with men. Serum leptin level is connected to bone
      resorption and also bone formation, both inversely related to serum leptin
      levels. The decrease in osteoclasia that accompanies increasing serum leptin
      levels does not seem to be related to an enhanced OPG effect because it was
      accompanied by decreased OPG levels. Low-turnover bone disease does not appear to
      be caused by increased serum leptin levels. The nature of the interrelation
      between serum leptin and PTH1-84 levels requires further study.

PMID- 14582048
TI  - Late referral to a nephrologist reduces access to renal transplantation.
AB  - BACKGROUND: Primary care physicians frequently request consultation with a
      nephrologist late in the treatment of patients with chronic kidney disease (CKD).
      Between 25% and 40% of referred CKD patients need renal replacement therapy (RRT)
      within 3 months of referral to a nephrologist. Late referral is associated with
      higher morbidity and worse long-term survival rates. The authors examined the
      effect of late referral on access to renal transplantation. METHODS: Data from
      the Australian end-stage renal disease (ESRD) registry (Australia and New Zealand
      Dialysis and Transplant Registry Database [ANZDATA]) regarding all ESRD patients
      aged 18 to 64, starting treatment between April 1995 and December 1998 were used.
      Excluding overseas visitors and patients commencing RRT outside Australia, the
      data encompassed 3,310 patients. Main outcome measures were: (1) acceptance onto
      a waiting list, (2) receipt of a transplant before March 31, 2000, and/or (3)
      receipt of a transplant during defined periods of RRT. RESULTS: Late referral
      patients were less likely to be put on the waiting list (odds ratio [OR], 0.49;
      95% confidence intervals [CI], 0.41 to 0.59) or given a transplant (hazard ratio,
      0.65; 95% CI, 0.55 to 0.77). Transplantation rates differed maximally during the
      first 3 months of RRT (OR, 0.21; 95% CI, 0.11 to 0.40) and were lower throughout
      RRT (OR in the period more than 2 years after commencing RRT, 0.67; 95% CI, 0.47
      to 0.96). CONCLUSION: Primary care physicians should refer patients at risk for
      ESRD earlier than is current practice. To improve access to transplantation and
      to achieve optimal outcomes of ESRD management, greater collaboration will be
      needed between primary care physicians and nephrologists.

PMID- 14582049
TI  - A comparison of persons who present for preemptive and nonpreemptive kidney
      transplantation.
AB  - BACKGROUND: Preemptive renal transplantation (PRT) has been associated with
      improved allograft and patient survival rates and requires that the medical
      evaluation for suitability for transplantation occurs before the initiation of
      maintenance dialysis. The aim of this study was to understand the factors
      associated with the timing of evaluation for renal transplantation relative to
      the initiation of dialysis. METHODS: In a prospective study, patients who
      presented to the Renal Transplant Evaluation Clinic at the Hospital of the
      University of Pennsylvania completed a self-administered questionnaire. RESULTS:
      Of the 290 patients included in the analysis, 44.5% were not yet on dialysis. Non
      dialysis-dependent persons had seen a nephrologist for a mean of 71.0 +/- 84.7
      months before transplant evaluation, whereas persons who presented for
      nonpreemptive evaluation reported first seeing a nephrologist a mean of 25.0 +/-
      42.8 months before dialysis initiation (P < 0.001). First learning about
      transplantation from somebody other than a nephrologist significantly increased
      the odds of undergoing nonpreemptive transplant evaluation (adjusted odds ratio
      [OR], 2.46; P = 0.01). The odds of nonpreemptive evaluation were decreased for
      every additional 3 months of chronic renal disease care by a nephrologist
      (adjusted OR, 0.96; P < 0.001) and significantly decreased if the patient
      reported having a spouse as a potential donor (adjusted OR, 0.41; P = 0.03).
      CONCLUSION: There is substantial opportunity for transplant evaluation before
      dialysis initiation that is not capitalized on and is affected by the duration of
      care provided by a nephrologist and the type of potential living donor.

PMID- 14582050
TI  - Thrombotic microangiopathy after renal transplantation in the United States.
AB  - BACKGROUND: Analysis of the incidence, time to event, and risk factors for
      thrombotic microangiopathy (TMA) after renal transplantation (RT), has not been
      reported in a national population. METHODS: This is a historical cohort study of
      15,870 RT recipients in the United States Renal Data System (USRDS) with Medicare
      as their primary payer between January 1, 1998, and July 31, 2000, followed until
      December 31, 2000. Patients with Medicare claims with a diagnosis of TMA
      (International Classification of Diseases, 9th Revision, codes 283.11x or 446.6x)
      after RT were assessed by Cox regression. RESULTS: Among patients with end-stage
      renal disease owing to hemolytic uremic syndrome (HUS), 29.2% later had TMA
      versus 0.8% of patients with ESRD owing to other causes. The incidence of TMA in
      RT recipients was 5.6 episodes per 1,000 person-years (PY; 189/1,000 PY; for
      recurrent TMA versus 4.9/1,000 PY for de novo TMA). The risk of TMA was highest
      for the first 3 months after transplant. Risk factors for de novo TMA included
      younger recipient age, older donor age, female recipient, and initial use of
      sirolimus. Patient survival rate after TMA was approximately 50% at 3 years.
      CONCLUSION: De novo TMA is uncommon and may occur later after RT than previously
      reported. Risk factors for de novo TMA were also identified.

PMID- 14582051
TI  - Severe acute respiratory syndrome in a hemodialysis patient.
AB  - Severe acute respiratory syndrome (SARS) is a highly infective disease caused by
      a newly identified coronavirus. We described the clinical course of the first
      long-term hemodialysis patient who developed SARS in the literature, and our
      experience in performing hemodialysis for this patient. Such patients may present
      with a less typical clinical picture, making diagnosis difficult. In this
      patient, the course of disease and duration of viral shedding was apparently
      prolonged, thus highlighting the need for increased infection control. Despite
      worsening the anemia in renal failure patients by causing hemolysis, ribavirin is
      well tolerated after dosage adjustment. Difficulties of diagnosis, infection
      control, and treatment of SARS in renal failure patients are discussed in this
      report.

PMID- 14582052
TI  - Clinical presentation and outcome of severe acute respiratory syndrome in
      dialysis patients.
AB  - There was a major outbreak of severe acute respiratory syndrome (SARS) affecting
      more than 300 patients occurring in a private housing estate in Hong Kong, in
      which an infected renal patient was suspected to be the primary source. It is
      unknown whether renal patients would represent a distinct group of patients who
      share some characteristics that could predispose them to have higher infectivity.
      In this context, we have encountered 4 dialysis patients contracting SARS in a
      minor outbreak, which involved 11 patients and 4 health care workers, in a
      medical ward of a regional hospital. Of these 4 dialysis patients, 1 patient was
      receiving hemodialysis while the other 3 patients were on continuous ambulatory
      peritoneal dialysis. Fever and radiological changes were their dominant
      presenting features. All were having positive results for SARS-associated
      coronavirus ribonucleic acid by reverse transcriptase-polymerase chain reaction
      performed on their nasopharyngeal aspirates or stool samples. It appeared that
      treatment with high-dose intravenous ribavirin and corticosteroids could only
      resolve the fever, but it could not stop the disease progression. All 4 patients
      developed respiratory failure requiring mechanical ventilation on days 9 through
      12. At the end, all of the patients died from sudden cardiac arrest, which was
      associated with acute myocardial infarction in 2 cases. From this small case
      series, it appeared that dialysis patients might have an aggressive clinical
      course and poor outcome after contracting SARS. However, a large-scale study is
      required to further examine this issue, and further investigation into the
      immunologic abnormalities associated with the uremic state in this group of
      patients is also warranted.

PMID- 14582053
TI  - Peritoneal dialysis.

PMID- 14582054
TI  - A 36-year-old man with a monoclonal gammopathy and nephrotic syndrome.

PMID- 14582055
TI  - Muscle infarction in peritoneal dialysis patients.

PMID- 14582056
TI  - Reactivity of iron compounds.

PMID- 14582057
TI  - Pharmacokinetics and utilization of iron sucrose.

PMID- 14582059
TI  - Interventional nephrology in federal health care system.

PMID- 14582061
TI  - Cardiac surgery in end-stage renal failure patients.

PMID- 14582069
TI  - Quiz page. Emphysematous pyelonephritis of the right kidney secondary to
      Escherichia coli, in the setting of diabetes mellitus.

PMID- 14582071
TI  - Sudden blindness caused by anterior ischemic optic neuropathy in 5 children on
      continuous peritoneal dialysis.
AB  - The authors report the occurrence of sudden blindness in 5 children (mean age, 32
      months; range, 11 to 60) during continuous peritoneal dialysis regimen. All
      children presented with loss of light perception, visual fixation and ocular
      pursuit, and bilateral mydriasis unreactive to bright light. Fundoscopic
      examination found signs of anterior ischemic optic neuropathy with disc swelling,
      edema, and hemorrhages. Whereas 1 patient was dehydrated, the 4 other patients
      appeared well and not dehydrated. Nevertheless, blood pressure was below the
      normal range in all of them. Therefore, hypovolemia is highly suspected to have
      been the cause of ischemic optic neuropathy in all cases. Treatment consisted of
      steroids (4 patients), anticoagulation or antiagregation drugs (3 patients),
      plasma or macromolecules infusions (2 patients), vasodilatators (2 patients), and
      transient dialysis interruption (1 patient). One child with hepatic cirrhosis
      died 4 days later of acute liver insufficiency owing to ischemic hepatic
      necrosis. The other children had only partial improvement of vision during the
      following months. Because the prognosis of ischemic optic neuropathy is very
      poor, diagnosis and treatment of chronic hypovolemia in children on continuous
      peritoneal dialysis is essential to prevent such a devastating complication.

PMID- 14582072
TI  - Renal tubular regeneration by bone marrow-derived cells in a girl after bone
      marrow transplantation.
AB  - Recent studies have indicated that bone marrow cells can contribute to
      regeneration of the kidney in experimental models. However, renal regeneration by
      apparent bone marrow-derived cells has not been shown previously in humans. The
      authors here report on a 7-year-old girl who received whole bone marrow
      transplantation from a male donor, and the contribution of bone marrow cells to
      the regeneration after renal damage was shown by in situ hybridization for the Y
      chromosome on autopsy specimens of the kidney. This observation suggests the
      clinical potential of bone marrow cells as a therapeutic option for renal injury.

PMID- 14582073
TI  - Use of tacrolimus in steroid- and cyclophosphamide-resistant minimal change
      nephrotic syndrome.
AB  - The authors report a case of adult-onset minimal change nephrotic syndrome (MCNS)
      that was resistant to steroid and cyclophosphamide therapy. Introduction of
      cyclosporin induced an usual cutaneous reaction of severe flushing attacks.
      Tacrolimus successfully alleviated both the nephrotic syndrome and the cutaneous
      side effect associated with cyclosporin use. The antiproteinuric mechanisms of
      tacrolimus and its potential in treating refractory MCNS and other forms of
      primary glomerulonephritides are discussed.

PMID- 14582074
TI  - Severe acidosis caused by starvation and stress.
AB  - A 1-year-old boy had severe anoxic brain injury owing to a cardiorespiratory
      arrest. He had an initial metabolic acidosis, but this largely resolved by
      hospital day 2. He then had a persistent, profound metabolic acidosis. Evaluation
      on hospital day 6 found that the patient had ketonemia, ketonuria, and a normal
      serum glucose level; he had received no intravenous dextrose during his
      hospitalization. The dextrose-free fluids were given initially to protect his
      brain from the deleterious effects of hyperglycemia after brain injury.
      Continuation beyond 24 hours was inadvertent. The initiation of dextrose
      containing intravenous fluids produced a rapid resolution of his metabolic
      acidosis. Starvation usually produces a mild metabolic acidosis, but when
      combined with physiologic stress, starvation may cause a severe metabolic
      acidosis. Among the few reports of severe starvation ketoacidosis, our case is
      unique because the patient was monitored closely in an intensive care unit,
      allowing us to describe the time course of the acidosis in detail.

PMID- 14582075
TI  - Preexisting crescentic glomerulonephritis in the renal allograft.
AB  - Two patients who received cadaveric renal transplants from the same donor were
      found to have similar diffuse proliferative glomerular lesions on renal biopsies
      performed for delayed graft function. The donor had no known disease, but had
      subtle abnormalities on preprocurement urinalysis. In retrospect, lupus nephritis
      is suspected in the donor. The authors detail the course of these 2 patients,
      review the literature on preexisting glomerular lesions, and address issues with
      regard to donor selection.

PMID- 14582077
TI  - MLL-rearranged leukemias: insights from gene expression profiling.
AB  - Gene expression analysis of human leukemias has provided insight into disease
      classification and mechanisms of oncogenesis. Its success is particularly evident
      for acute leukemias with rearrangement of the mixed lineage leukemia (MLL) gene
      on chromosome 11q23. Unlike most other recurrent translocations, MLL
      rearrangements are found in leukemias classified as acute myelogenous leukemia
      (AML) or acute lymphoblastic leukemia (ALL). In addition, MLL-rearranged
      leukemias often express both myeloid- and lymphoid-associated genes. These
      unusual characteristics have generated much interest in the cell of origin and
      the mechanism of transformation by MLL rearrangements. Here we review insights
      gained from characterization of MLL-rearranged human leukemias by genome-wide
      expression profiling and compare these to data from model systems.

PMID- 14582078
TI  - Gene expression profiling in T-cell acute lymphoblastic leukemia.
AB  - T-cell acute lymphoblastic leukemia (T-ALL) presents a difficult medical problem.
      T-ALL's clinical features and the biological properties of the leukemia cells are
      not predictive of prognosis, and thus have not been useful for risk-specific
      adjustments in therapeutic intensity. Microarray gene expression analyses of T
      cell leukemic lymphoblasts have not only improved our understanding of the
      biological heterogeneity of this disease but have revealed clinically relevant
      molecular subtypes. Five different multistep molecular pathways have been
      identified that lead to T-ALL, involving activation of different T-ALL oncogenes:
      (1) HOX11, (2) HOX11L2, (3) TAL1 plus LMO1/2, (4) LYL1 plus LMO2, and (5) MLL
      ENL. Gene expression studies indicate activation of a subset of these genes
      HOX11, TAL1, LYL1, LMO1, and LMO2-in a much larger fraction of T-ALL cases than
      those harboring activating chromosomal translocations. In many such cases, the
      abnormal expression of one or more of these oncogenes is biallelic, implicating
      upstream regulatory mechanisms. Among these molecular subtypes, overexpression of
      the HOX11 orphan homeobox gene occurs in approximately 5% to 10% of childhood and
      30% of adult T-ALL cases. Patients with HOX11-positive lymphoblasts have an
      excellent prognosis when treated with modern combination chemotherapy, while
      cases at high risk of early failure are included largely in the TAL1- and LYL1
      positive groups. Supervised learning approaches applied to microarray data have
      identified a group of genes whose expression is able to distinguish high-risk
      cases. Further analyses of gene expression signatures of T-ALL lymphoblasts are
      especially needed for patients treated on modern combination chemotherapy trials
      to clearly distinguish the 10% to 15% of patients who fail induction or relapse
      in the first year of treatment. These high-risk patients would be ideal
      candidates for more intensive therapies in first remission, such as myeloablative
      regimens with stem cell rescue. Based on the rapid pace of research in T-ALL,
      made possible in large part through microarray technology, deep analysis of
      molecular pathways should lead to new and much more specific targeted therapies.

PMID- 14582079
TI  - Gene expression profiling as a tool for the diagnosis of acute leukemias.
AB  - The standard methods to diagnose leukemia are cytomorphology and, in some cases,
      histology, which both are supplemented by cytochemistry and multiparameter
      immunophenotyping. Cytogenetics, fluorescence in situ hybridisation (FISH), and
      polymerase chain reaction (PCR) assays add important information and allow
      comprehensive diagnosis of well-defined subentities today. In the clinic, better
      understanding of the course of distinct, biologically defined disease subtypes is
      the basis for a selection of specific therapeutic approaches. As knowledge on
      deregulated pathways in leukemia accelerates the development of new therapeutics,
      a detailed and comprehensive diagnostic tool is required. The microarray
      technology that quantifies gene expression intensities of thousands of genes in a
      single analysis has the potential to become essential for the molecular
      classification of leukemias. Microarrays may be used routinely for diagnostic
      purposes in the near future. Gene expression profiling should also lead to the
      detection of new biological and clinically relevant subtypes in leukemia and
      therefore guide therapeutic decisions.

PMID- 14582081
TI  - Toward the identification of distinct molecular and clinical entities of multiple
      myeloma using global gene expression profiling.
AB  - Multiple myeloma (MM) is a poorly understood and uniformly fatal malignancy of
      antibody-secreting plasma cells (PC). Although several key molecular events in
      disease initiation or progression have been confirmed (such as 14q32
      translocations) or implicated (chromosome 13 deletion), a unifying mechanism of
      myelomagenesis has proved elusive. Furthermore, while MM is generally
      indistinguishable morphologically, the disease exhibits tremendous variability in
      its clinical course, with some patients surviving only months and others many
      years, suggesting that MM is composed of distinct clinical entities. As abnormal
      gene expression is central to most, if not all cancers, high-throughput global
      gene expression profiling has become a powerful tool to investigate the molecular
      biology and clinical behavior of malignancy. Here we discuss recent progress made
      in the development of molecular-based diagnostics and prognostics for MM through
      the dissection of the transcriptome of PCs from healthy individuals and patients
      with MM and other PC dyscrasias.

PMID- 14582080
TI  - Towards molecular diagnosis and targeted therapy of lymphoid malignancies.
AB  - Gene expression profiling of cancer began as a research tool but is rapidly
      moving towards clinical application. The diagnostic category of diffuse large B
      cell lymphoma (DLBCL) can now be viewed as an amalgam of several different
      diseases that have distinct gene expression profiles, oncogenic mechanisms, and
      clinical outcomes. Other diagnostic categories such as chronic lymphocytic
      leukemia (CLL) have a single gene expression signature that distinguishes them
      from other lymphoid malignancies. Nevertheless, elevated expression of a single
      gene, ZAP-70, is characteristic of a more aggressive subtype of CLL that may
      require novel treatment approaches. In mantle cell lymphoma (MCL), a quantitative
      measurement of gene expression associated with tumor proliferation is a powerful
      predictor of survival. Ultimately, the molecular diagnosis of these malignancies
      will identify molecular pathways that can be exploited for therapy. For example,
      one of the gene expression subgroups of DLBCL, termed activated B-cell like
      DLBCL, is characterized by constitutive activation of the nuclear factor-kappaB
      (NF-kappaB) signaling pathway, and interference with this pathway selectively
      kills these lymphoma cells. The full benefit of gene expression profiling can
      only be realized if we incorporate this technology into prospective clinical
      trials.

PMID- 14582082
TI  - Genetic variation and hematology: single-nucleotide polymorphisms, haplotypes,
      and complex disease.
AB  - In the course of generating a draft sequence of the human genome, we now
      recognize the enormous scope of genetic variation among humans, which can be used
      to probe the genetics of complex diseases such as leukemia or thrombosis. There
      is already mounting evidence of new susceptibility genes and genes that interact
      with environmental factors. Genetic variants, especially single-nucleotide
      polymorphisms (SNPs), also can be utilized to investigate potential modifiers of
      disease. Genetic variation can be applied to study pharmacogenomics, which could
      eventually drive the choice of therapeutic and interventional strategies. The
      genomic revolution ultimately should give insights into key mechanisms in
      hematological disorders that can be translated into targeted therapies.

PMID- 14582090
TI  - The prehospital administration of intravenous methylprednisolone lowers hospital
      admission rates for moderate to severe asthma.
AB  - OBJECTIVE: To compare hospital admission rates for patients with moderate to
      severe asthma who receive intravenous methylprednisolone given in the prehospital
      setting versus in the emergency department. METHODS: A retrospective chart review
      was used to identify emergency medical services (EMS) transports of patients with
      moderate to severe asthma when 125 mg methylprednisolone was given intravenously
      in the prehospital setting under existing regional protocols. Data were collected
      on EMS runs in an urban/suburban system from May 1, 2000, through April 30, 2001.
      Only patients 18 to 50 years old with a history of asthma were included in the
      study. Patients were excluded if they left against medical advice, were long-term
      smokers, used home oxygen, or had a history of chronic obstructive pulmonary
      disease. A parallel search was performed from February 1, 1999, to April 30,
      2000, to identify moderate-severe asthmatics who were transported by EMS and
      later given intravenous methylprednisolone in the emergency department. During
      this period, methylprednisolone was not available for use in this EMS system.
      RESULTS: A total of 31 moderate to severe asthmatics were identified as receiving
      prehospital methylprednisolone. A total of 33 asthmatics were identified who were
      transported by EMS and later received intravenous methylprednisolone in the
      emergency department. Average patient age in the prehospital methylprednisolone
      group was 34+/-10 years (mean+/-standard deviation; 95% confidence interval
      [CI]=31-37). Average age in the hospital group was 34+/-10 years (95% CI=31-37).
      Average time to administration of methylprednisolone in the prehospital setting
      was 15+/-7 minutes (95% CI=7-22). The average time elapsed in the emergency
      department before methylprednisolone was 40+/-22 minutes (95% CI=23-57). Only
      12.9% (4) of the patients receiving prehospital solumedrol were admitted versus
      33.3% (11) of those receiving the medication in the emergency department
      (p=0.025). Patients were 3.375 times more likely to be admitted if they received
      methylprednisolone in the emergency department versus in the prehospital setting.
      CONCLUSION: Patients with moderate to severe asthma who receive intravenous
      methylprednisolone in the prehospital setting have significantly fewer hospital
      admissions.

PMID- 14582091
TI  - Cardiac arrest and resuscitation epidemiology in Singapore (CARE I study).
AB  - OBJECTIVES: To describe the epidemiology of out-of-hospital cardiac arrest (OHCA)
      in Singapore, the emergency medical services (EMS) response, and to identify
      possible areas for improvement. METHODS: This prospective observational study
      constitutes phase I of the Cardiac Arrest and Resuscitation Epidemiology (CARE)
      project. Included were all patients with nontraumatic OHCA conveyed by the
      national emergency ambulance service. Patient characteristics, cardiac arrest
      circumstances, EMS response, and outcomes were recorded according to the Utstein
      style. RESULTS: From October 1, 2001, to April 30, 2002, 548 patients were
      enrolled into the study. Mean (standard deviation [SD]) age was 62.2 (17.9)
      years, with a male predominance (65.6%). A total of 59.8% of collapses occurred
      at home, 35.3% of arrests were not witnessed, and bystander cardiopulmonary
      resuscitation was present for 20.6%. Mean (SD) time from collapse to call
      received by EMS was 10.6 (13.1) minutes. Mean (SD) EMS response time was 10.2
      (4.3) minutes. Mean (SD) time from call to defibrillation was 16.7 (7.2) minutes.
      Mean (SD) on-scene time was 9.9 (4.5) minutes. First presenting rhythm at the
      scene was asystole in 54.5%, pulseless electrical activity 22.9%, ventricular
      fibrillation 19.6%, and ventricular tachycardia 0.4%. Of all cardiac arrests, 351
      had resuscitation attempted and were of cardiac origin. Among these patients,
      17.9% had return of spontaneous circulation, 8.5% survived to hospital admission,
      and 2.0% survived to discharge. CONCLUSION: CARE I establishes the baseline for
      the evaluation of incremental introduction of prehospital Advanced Cardiac Life
      Support interventions planned for future phases. Continuing efforts should be
      made to strengthen all chains of survival. This represents the most comprehensive
      OHCA study yet conducted in Singapore.

PMID- 14582093
TI  - Derivation of emergency medical services dispatch codes associated with low
      acuity patients.
AB  - OBJECTIVE: To identify emergency medical services (EMS) dispatch codes associated
      with basic life support (BLS) level of prehospital care, a proxy for low illness
      acuity. METHODS: This retrospective cohort study was conducted in an urban city
      with a single advanced life support level EMS provider. The 911 center was
      certified in using dispatch protocols from Priority Dispatch Corporation (Salt
      Lake City, UT). Dispatch data on all transported EMS patients from August 2001 to
      April 2002 were abstracted. The authors prospectively defined a low-acuity
      patient as one who received BLS-level care and defined a low-acuity dispatch code
      as one in which at least 90% of coded patients required only BLS care. For each
      dispatch code or code group, the authors calculated the fraction of patients who
      received BLS-level care. For each "A"-level (lowest category) dispatch code
      group, the fraction of patients receiving BLS-level care was also evaluated.
      RESULTS: A total of 19,332 calls met inclusion criteria and were categorized into
      118 dispatch codes or code groups. Twenty-eight codes or code groups with 7,801
      patients met the authors' definition of low acuity. Overall, 7,394 patients
      received only BLS care (94.8%, 95% confidence interval: 94.3%-95.3%). Analysis of
      "A"-level dispatch code groups found BLS use rates of 52.8% to 99.3%.
      CONCLUSIONS: Certain dispatch codes are associated with the delivery of BLS-level
      care, indicating identification of patients likely to be low acuity. These codes
      are not necessarily "A"-level dispatch codes, which are commonly considered to
      represent the lowest-acuity patients. Future studies are needed to prospectively
      validate that these codes do represent low-acuity patients.

PMID- 14582094
TI  - Concordance of field and emergency department assessment in the prehospital
      management of patients with dyspnea.
AB  - OBJECTIVE: Dyspnea is a common complaint of patients treated by emergency medical
      services (EMS). Few studies have examined the ability of paramedics to
      distinguish between etiologies of dyspnea. The authors evaluated the degree of
      agreement related to cardiac versus noncardiac sources of dyspnea between field
      and emergency department (ED) assessment of patients transported at the advanced
      life support level. METHODS: This was a retrospective, cohort study of
      consecutive patients aged > or =35 years transported by paramedics with dyspnea.
      The authors compared the concordance between the EMS and ED diagnoses. They also
      investigated whether patients whose assessments were discordant had worse
      outcomes. RESULTS: Paramedics correctly assessed the cause of dyspnea in 172 of
      222 (77%) patients (kappa=0.60; 95% confidence interval [CI]=0.51, 0.69). Among
      single-source (i.e., cardiac or noncardiac) dyspnea patients, prehospital
      providers correctly assessed 70 of 84 (83%) noncardiac causes and 98 of 114 (86%)
      cardiac causes (kappa=0.69; 95% CI=0.59, 0.79). When the ED diagnosis included
      both cardiac and noncardiac etiologies, paramedics treated seven of 24 (29%)
      patients as noncardiac, 13 of 24 (54%) as cardiac, and four of 24 (17%) as
      combined-source dyspnea. The authors did not observe any statistically
      significant differences in in-hospital mortality, intubation frequency, or
      hospital length of stay in patients whose prehospital dyspnea diagnosis was
      discordant. CONCLUSION: The authors conclude that in this EMS system, field
      assessment of dyspnea by paramedics is in agreement with that arrived at in the
      ED in a high proportion of patients with dyspnea from a single source. However,
      field assessment of dyspnea from multiple etiologies is less concordant.

PMID- 14582095
TI  - Time to analgesia for patients with painful extremity injuries transported to the
      emergency department by ambulance.
AB  - OBJECTIVE: To measure the time to analgesia for patients with painful, isolated
      extremity injuries brought to the emergency department (ED) by emergency medical
      services (EMS). METHODS: A retrospective chart review of all patients presenting
      with isolated, painful extremity injuries during an 18-month period to a Level 1
      trauma center. Medical records were reviewed by diagnostic codes for extremity
      injuries. INCLUSION CRITERIA: patients 18 years or older transported to the ED by
      EMS; isolated, painful extremity injuries; received parenteral analgesia in the
      ED or by EMS. Excluded: multiple trauma patients, interfacility transfers,
      hemodynamically unstable patients, head-injured patients, intoxicated patients,
      and patients with mental status changes. Data elements: age, sex, EMS arrival
      time, EMS medication time, hospital triage time, and ED medication time. All
      "times to analgesia" were calculated from the EMS arrival time on scene. RESULTS:
      Extremity injuries were identified in 706 patients. Of these, 104 patients with
      painful, isolated, extremity injuries met all inclusion criteria. Thirteen
      (12.5%) of 104 received analgesia by EMS during prehospital care. Ninety-one
      patients (88%) first received parenteral analgesia in the ED. The mean time to
      analgesia for EMS treated patients was 23 minutes (95% CI 16.7-30.2). Mean time
      to analgesia for patients treated in the ED was 113 minutes (95% CI 99.2-128.1).
      Mean time to analgesia after triage in this group was 75 minutes (95% CI 60.8
      89.7). CONCLUSION: In this study, patients received analgesia sooner when
      administered by EMS during prehospital care. There was a significant time delay
      after triage for patients first medicated in the ED.

PMID- 14582096
TI  - Pediatric restraint use is associated with reduced transports by emergency
      medical services providers after motor vehicle crashes.
AB  - OBJECTIVE: To determine the association between pediatric restraint use during
      motor vehicle crashes and patient transports by emergency medical services (EMS)
      providers. METHODS: Children under 16 years of age who were involved in motor
      vehicle crashes in Houston or Harris County, Texas, in 1997 were identified from
      Texas Department of Public Safety (DPS) crash data. DPS data were linked
      probabilistically to City of Houston Fire Department EMS data to identify whether
      the children were transported from the scene by EMS. Odds ratios were calculated
      to determine the association between restraint use and EMS transport. Logistic
      regression was used to control for age and injury severity in this relationship.
      RESULTS: From the linked data for 1997, 1,696 children were involved in reported
      automobile or truck crashes to which EMS responded. Of the 1,580 children about
      whom information concerning restraint use was available, 1,309 (83%) were wearing
      some type of safety restraint and 1,342 (85%) were transported by EMS. Adjusting
      for injury severity, children wearing safety restraints during motor vehicle
      crashes were 60% (95% confidence interval 34-75%) less likely to be transported
      by EMS than those not wearing safety restraints during such crashes. CONCLUSIONS:
      The use of safety restraints during motor vehicle crashes is associated with a
      reduction in the number of children transported from the scene by EMS providers.
      This effect is independent of age and injury severity.

PMID- 14582097
TI  - A comparison of first-responder automated external defibrillator (AED)
      application rates and characteristics of AED training.
AB  - OBJECTIVE: To determine whether there were associations between the
      characteristics of first-responder automated external defibrillator (AED)
      training and AED application rates. METHODS: This multicenter retrospective
      cohort study analyzed data from ten emergency medical services systems where
      first responders were trained and equipped with AEDs. Data were provided for all
      out-of-hospital cardiac arrests (OHCAs) occurring over two years, including
      whether the first-responder AED was applied (pads attached to patient). Systems
      were surveyed to determine the characteristics of their initial and continuing
      AED training. Data were analyzed using odds ratios (ORs) with 95% confidence
      intervals (95% CIs). RESULTS: Overall, the first-responder AED was applied to 53%
      of 2,181 OHCAs. First responders applied AEDs to 60% of OHCAs when a national AED
      training curriculum was used and to 49% of OHCAs when a locally created
      curriculum was used (OR=1.58; 95% CI=1.32-1.88). First responders applied AEDs to
      61% of OHCAs when they were trained to the level of Certified First Responder or
      higher and to 28% of OHCAs when they were trained only in cardiopulmonary
      resuscitation (OR=3.97; 95% CI=3.20-4.93). First responders applied AEDs to 66%
      of OHCAs when they each had an opportunity to apply the AED during continuing
      training and to 17% of OHCAs when they did not have this opportunity (OR=9.04;
      95% CI=7.15-11.42). First responders applied AEDs to 59% of OHCAs when they had
      not received continuing training within one year of their initial training and to
      42% of OHCAs when they had received continuing training in the first year
      (OR=2.00; 95% CI=1.67-2.40). CONCLUSION: Use of a national AED training
      curriculum, training to the level of Certified First Responder or higher, and the
      ability for each first responder to apply the AED during continuing training were
      associated with higher AED application rates. Continuing training within the
      first year did not appear to be as important as actually using the AED during the
      training.

PMID- 14582100
TI  - Prospective determination of medical necessity for ambulance transport by
      paramedics.
AB  - OBJECTIVE: It has been estimated that between 11% and 61% of ambulance transports
      to emergency departments are not medically necessary. This study's objective was
      to analyze paramedic ability to determine the medical necessity of ambulance
      transport to the emergency department. METHODS: Paramedics prospectively assessed
      adult patients transported to an emergency department during a six-week period.
      The setting was an urban, all advanced life support, public utility model
      emergency medical services (EMS) system with 58,000 transports per year.
      Paramedics determined medical necessity of patient transport based on the
      following five criteria: 1) need for out-of-hospital intervention; 2) need for
      expedient transport; 3) potential for self-harm; 4) severe pain; or 5) other. On
      arrival in the emergency department, the emergency physician made a blinded
      determination based on the same criteria. Kappa statistics were used to assess
      agreement. RESULTS: Data forms were completed on 825 of 1,420 (58%) patients
      transported. Emergency physicians determined 248 (30%) transports were not
      necessary, paramedics 236 (29%), with agreement in 76.2% (K=0.42) of cases.
      Paramedics undertriaged 92 patients (11%). Rates of agreement on the five
      criteria were: 1) 71.9% (K=0.43); 2) 77.7% (K=0.22); 3) 89.6% (K=0.40); 4) 89.6
      (K=0.32); and 5) 82.2% (K=0.29). CONCLUSIONS: Paramedics and emergency physicians
      agreed that a significant percentage of patients did not require ambulance
      transport to the emergency department. Despite only moderate agreement regarding
      which patients needed transport, the undertriage rate was low.

PMID- 14582099
TI  - Prehospital hypoglycemia: the safety of not transporting treated patients.
AB  - OBJECTIVES: Emergency medical services (EMS) personnel frequently encounter
      patients who refuse transport after being treated for a hypoglycemic episode. The
      outcomes of most of these patients are unknown. The purpose of this study was to
      determine the outcomes of patients treated and not transported for hypoglycemia
      and identify criteria that could be used to identify patients who did not require
      transport to hospital. METHODS: This was a prospective, observational study
      involving all adult (>15 years) hypoglycemic patients (blood glucose less than 4
      mmol/L by glucometer) attended to by the EMS system in the Halifax Metropolitan
      area in the province of Nova Scotia during a ten-month interval. RESULTS: There
      were 220 calls for adult patients with hypoglycemia. Of the 75 calls that
      resulted in transport, there were 17 further hypoglycemic episodes requiring a
      repeat call for an ambulance (22.7%) and three recurrences (4%). Of the 145 calls
      that did not result in transport, 40 further episodes of hypoglycemia (27.6%) and
      three recurrences (2%) were reported. These differences were not statistically
      significant (p=0.43 and 0.33, respectively). There was also no statistically
      significant difference in the intervals between hypoglycemic episodes for
      patients transported (51.1 days +/-65) compared with patients not transported for
      their previous hypogylcemic episode (40.7 days +/-53.5) (p=0.6). Of the 47 calls
      entered in the study, there were seven repeat calls for hypoglycemia (15%) and
      one recurrence (2.1%). The majority of patients did not follow up with their
      physician. CONCLUSIONS: Repeat episodes of hypoglycemia are common; however,
      recurrences within 48 hours are not. Admission to hospital is rarely required.
      There appears to be no difference in the incidence of recurrences and repeat
      episodes of hypoglycemia between transported and nontransported insulin-dependent
      patients, regardless of age. Given the high incidence of repeat episodes,
      paramedics and physicians need to emphasize the importance of follow-up.

PMID- 14582101
TI  - Blind tracheal intubation by paramedics through the LMA-Unique.
AB  - OBJECTIVE: The manufacturer of the laryngeal mask airway (LMA) reports success
      rates of 30-93% by practitioners attempting tracheal intubation through the LMA
      Classic. No prior studies describe success rates through the (disposable) LMA
      Unique by paramedics. The objective of this study was to measure the success rate
      of paramedics attempting to intubate the trachea blindly through the LMA-Unique.
      METHODS: During a paramedic refresher class and an emergency medical services
      teaching day conference, paramedics previously trained in the use of the LMA
      Unique as a "rescue" airway device were instructed in the technique of tracheal
      intubation through the LMA-Unique. A Laerdal LMA-mannequin was immobilized with
      an extrication collar and held by an investigator in the head-neutral position.
      Paramedics were first asked to insert the LMA-Unique as previously trained, and
      to confirm adequate ventilation by seeing inflation of the mannequin's lungs.
      Then, subjects were asked to pass a well-lubricated 6-0 Mallinckrodt endotracheal
      tube through the LMA-Unique within a 60-second period. Tracheal placement of the
      endotracheal tube was then confirmed by visualization of the expanding mannequin
      lungs. Rates of success of LMA-Unique placement and endotracheal tube placement
      were measured. RESULTS: Fifty of the 52 (96%; CI 91% to 100%) paramedics
      successfully inserted the LMA-Unique on the first attempt. Only 11 of the 52
      (21%; CI 10% to 32%) paramedics were successful in blind placement of the
      endotracheal tube into the trachea through the LMA-Unique within a 60-second
      period. The failures (41 of the 52) were visually confirmed to be located in the
      esophagus. CONCLUSION: In this study, when attempting blind tracheal intubation
      through the LMA-Unique, paramedics were rarely successful in tracheal placement.
      Basic LMA-Unique insertion, however, had a very high success rate.

PMID- 14582102
TI  - The incidence and treatment of prehospital motion sickness.
AB  - OBJECTIVES: The authors' objectives were: 1) to determine the incidence of motion
      sickness during ambulance transport on a mountainous route in healthy volunteers,
      and 2) to determine if droperidol alleviated the signs and symptoms of motion
      sickness in those volunteers who developed it. METHODS: This was a prospective,
      randomized, double-blind, placebo-controlled trial. Subjects were healthy
      volunteers over age 18 and not currently taking an antiemetic. Participants were
      transported in the back of an ambulance over a mountainous road. Those who
      developed motion sickness rated their nausea on a 100-mm visual analog scale
      (VAS) and were randomized to receive placebo (saline) or 2.5 mg droperidol
      intravenously. Symptoms were recorded on a VAS every 5 minutes until the end of
      the transport. Incidence of motion sickness was calculated as a percentage with
      95% confidence intervals (CIs). Pretreatment characteristics were compared with
      chi-square tests, and mean VAS scores were compared using t-tests. RESULTS:
      Thirty-seven subjects completed the study. Sixteen (43%, 95% CI=27%-59%)
      developed motion sickness. Fifteen were randomized and completed data collection.
      Eight received droperidol (mean baseline VAS, 45) and seven received placebo
      (mean baseline VAS, 40). Droperidol trended toward a greater mean reduction of
      nausea than placebo at 5 minutes (20 versus 4, p=0.077). CONCLUSIONS: The
      incidence of motion sickness during ambulance transport in a mountainous setting
      is substantial. There was a strong trend toward a positive treatment effect with
      droperidol. Further prospective study in an actual patient setting is warranted.

PMID- 14582103
TI  - Emergency medical services in St. Vincent and the Grenadines.
AB  - OBJECTIVE: This descriptive study reports the status of the health care
      infrastructure and the emergency medical services system in the nation of St.
      Vincent and the Grenadines, an eastern Caribbean nation made up of a series of
      small islands located 1,600 miles southeast of Miami. METHODS: Data regarding the
      health care system and emergency medical services in the nation were gathered
      from various sources, including the Ministry of Health, government publications,
      hospital records, accident and emergency department logbooks, and interviews with
      physicians, nurses, and ambulance workers. RESULTS: The health system is similar
      in structure to that of the United Kingdom. Generally, the health infrastructure
      and available staffing are adequate and comparable to those of developed nations.
      However, out-of-hospital emergency medical services are lacking in both equipment
      and trained personnel. CONCLUSION: These data should be useful to both
      policymakers and health professionals in formulating strategies for advancing
      emergency medical services in St. Vincent and the Grenadines, and may also be
      instructive to other countries with developing emergency medical services
      systems.

PMID- 14582104
TI  - Prehospital pain management.

PMID- 14582121
TI  - Synthesis, in vitro and in vivo evaluation of a delivery system for targeting
      anticancer drugs to the brain.
AB  - A 1, 4-dihydropyridine <--> pyridinium salt type redox system is described as a
      general and flexible method for site-specific and sustained delivery of drugs to
      the brain. This concept was used in the present investigation as a model to
      deliver an alkylating antitumor agent into the brain. A bis-(chloroethyl)amine
      drug was hooked to 1, 4-dihydropyridine chemical delivery system (CDS) through an
      amide linkage. Five new-target compounds (23-27) of the 1, 4-dihydropyridine CDS
      type were synthesized through the reduction of five new pyridinium quaternary
      intermediates (18-22). The synthesized 1, 4-dihydropyridines were subjected to
      various chemical and biological investigations to evaluate their ability to cross
      the blood-brain barrier (BBB), and to be oxidized biologically into their
      corresponding quaternary compounds. The in vitro oxidation studies showed that 1
      benzyl-3-[N-[2-bis(2-chloroethyl)aminoethyl]-carbamoyl]-1, 4-dihydropyridine (23)
      and 1-(4-nitrobenzyl)-3-[N-[2-bis(2-chloroethyl)aminoethyl ]carbamoyl]-1, 4
      dihydropyridine (27) could be oxidized into their corresponding quaternary
      compounds 18 and 22 respectively, at an adequate rate, which ensure the release
      of the carried anticancer drug. The in vivo studies showed that compound 23 was
      able to cross the BBB at detectable concentrations. On the other hand, the in
      vitro alkylation activity studies revealed that 1-(4-nitrobenzyl)-3-[N-[2-bis(2
      chloroethyl)aminoethyl]carbamoyl]pyridinium bromide (22) is an alkylating agent
      with activity comparable to the known drug chlorambucil.

PMID- 14582122
TI  - Invesgations [correction investigations] on the influence of halide substituents
      on the estrogen receptor interaction of 2, 4, 5-tris(4-hydroxyphenyl)imidazoles.
AB  - Previously, we reported on the synthesis and estrogen receptor (ER) interaction
      of imidazoles, which had to be 1-alkyl-4, 5-bis(2-halo-4-hydroxyphenyl)
      substituted for a high relative binding affinity (RBA >1 %). This led to the
      assumption that a shielding of the polar heterocyclic system is a prerequisite
      for ER binding. In continuation of this study we synthesized 2, 4, 5-tris(4
      hydroxyphenyl)imidazoles with Cl-or F-atoms in the ortho-positions of the
      aromatic rings and evaluated whether they mediate sufficient hydrophobicity for
      ER interaction. 2-(2, 6-Dichloro-3/4-hydroxyphenyl)-4, 5-bis(2-halo-4
      hydroxyphenyl)imidazoles were synthesized by reaction of the respective methoxy
      substituted benzil with either the 2, 6-dichloro-4-methoxy-or the 2, 6-dichloro-3
      methoxybenzaldehyde in ammonium acetate solution. The required ether cleavage was
      performed subsequently with BBr(3). In the competition experiment with
      [(3)H]estradiol the imidazoles with the a C2-standing (2, 6-dichloro-4
      hydroxyphenyl) ring showed an RBA >0.02 %, but did not activate the luciferase
      gene in estrogen receptor positive MCF-7-2a breast cancer cells stably
      transfected with the plasmid ERE(wtc)luc. In the test for antagonistic potency
      only the 2-(2, 6-dichloro-4-hydroxyphenyl)-4, 5-bis(4-hydroxyphenyl)imidazole 3
      antagonized the effects of 1 nM estradiol slightly. From these data, it can be
      concluded that a C2-standing 2, 6-dichloro-4-hydroxyphenyl ring is not
      appropriate to optimize the ER interaction of 4, 5-(4-hydroxyphenyl)imidazoles.

PMID- 14582123
TI  - Dopamine receptor ligands. Part VII [1]: novel 3-substituted 5-phenyl-1, 2, 3, 4,
      5, 6-hexahydro-azepino-[4, 5-b]indoles as ligands for the dopamine receptors.
AB  - A number of 5-phenyl-1, 2, 3, 4, 5, 6-hexahydro-azepino-[4, 5-b]indoles 3 were
      synthesized with different substituents at the azepine-N position (methyl-, allyl
      , 2-phenyl-ethyl-, cyclopropylmethyl- and unsubstituted). Furthermore, the indole
      N-methylated compound was generated and by using norephedrines and
      norpseudoephedrines as a chiral pool, 4-methyl-5-phenyl-1, 2, 3, 4, 5, 6
      hexahydro-azepino-[4, 5-b]indoles were prepared which contained racemisation at
      the reacting C-atom. These compounds, as well as the ring-open amino-alcohols,
      were screened for their affinity to the hD(1)-, hD(5)-, hD(2L)-, and hD(4)
      receptors (c please check sentence). They had micromolar affinities for the
      receptors and showed the highest affinity to the D(1)-subtype family. The cyclic
      compounds possessed the highest affinity, with the cyclopropylmethyl-(3c) and
      methyl-substituents (3 e) being the most active of the tested compounds. Based on
      an intracellular cAMP-assay, the unsubstituted compound (at the azepine-N
      position) turned out to be an agonist for the D(1)-and D(5)-subtype family,
      whereas the substituted compounds showed (partial) agonistic, or even inverse
      agonistic activity.

PMID- 14582124
TI  - 4-(5-chloro-2(3H)-benzoxazolon-3-yl) butanoic acid derivatives: synthesis,
      antinociceptive and anti-inflammatory properties.
AB  - In this study, 4-(5-chloro-2(3H)-benzoxazolone-3-yl)butanoic acid and its ethyl
      ester as well as its ten new amide derivatives have been synthesized. Their
      structures have been elucidated by IR, (1)H-NMR spectra and elemental analysis.
      The compounds were screened for antinociceptive and anti-inflammatory activities.
      The highest antinociceptive and anti-inflammatory activities were exhibited by
      Compound 11 which has carboxylic acid structure. A various decrease in
      antinociceptive and anti-inflammatory activity was observed by amidation of the
      carboxylic acid moiety of this compound.

PMID- 14582127
TI  - Primates as pets in Mexico City: an assessment of the species involved, source of
      origin, and general aspects of treatment.
AB  - The large human populations in cities are an important source of demand for
      wildlife pets, including primates, and not much is known about the primate
      species involved in terms of their general origin, the length of time they are
      kept as pets, and some of the maintenance problems encountered with their use as
      pets. We report the results of a survey conducted in Mexico City among primate
      pet owners, which was aimed at providing some of the above information. We used
      an ethnographic approach, and pet owners were treated as informants to gain their
      trust so that we could enter their homes and learn about the life of their
      primate pets. We surveyed 179 owners of primate pets, which included 12 primate
      species. Of these, three were native species (Ateles geoffroyi, Alouatta pigra,
      and A. palliata). The rest were other neotropical primate species not native to
      Mexico, and some paleotropical species. Spider monkeys and two species of howler
      monkeys native to Mexico accounted for 67% and 15%, respectively, of the primate
      cases investigated. The most expensive primate pets were those imported from
      abroad, while the least expensive were the Mexican species. About 45% of the
      native primate pets were obtained by their owners in a large market in Mexico
      City, and the rest were obtained in southern Mexico. Although they can provide
      companionship for children and adults, primate pets are subject to a number of
      hazards, some of which put their lives at risk. The demand by city dwellers for
      primate pets, along with habitat destruction and fragmentation, exerts a
      significant pressure on wild populations in southern Mexico.

PMID- 14582128
TI  - Proximity patterns of female western lowland gorillas (Gorilla gorilla gorilla)
      during the six months after parturition.
AB  - Studies of wild mountain gorillas have demonstrated strong preferences among new
      mothers for the silverback. Protection against infanticide has been theorized to
      be the primary cause for this attraction. We examined social partner preferences
      in captive western lowland mothers during the 6 mo after parturition and found
      that juveniles and females were the primary members of the new mothers' social
      network. Mothers spent significantly more time in close proximity with both of
      these subgroups than with the silverback. Proximity patterns changed over time:
      new mothers spent more time near females in the month after parturition than in
      the month prior to parturition, and spatial proximity increased again in months 2
      6 postparturition. These findings differ from those reported for wild mountain
      gorillas, which may reflect the lack of infanticide risk in captivity. Given
      current hypotheses that infanticide may be a limited in western lowland gorillas,
      the social partner preferences observed here may be indicative of patterns in
      wild populations.

PMID- 14582129
TI  - Personality influences tetanus-specific antibody response in adult male rhesus
      macaques after removal from natal group and housing relocation.
AB  - Previous research has suggested that personality is related to immune function in
      macaques. Using a prospective design, we examined whether variation in the
      personality dimension "Sociability" in adult male rhesus macaques (Macaca
      mulatta) was related to the in vivo secondary antibody response to a tetanus
      toxoid booster immunization following removal from natal groups and relocation to
      individual housing. We also explored whether the timing of the immunization
      following relocation had an impact on the immune response. Blood was sampled at
      the time of booster immunization, at 14 and 28 days post-immunization, and
      approximately 9 months post-immunization. Plasma was assayed for tetanus-specific
      IgG by enzyme-linked immunoassay (ELISA). There was no difference between High-
      and Low-Sociable animals in antibody levels at the time of the booster
      immunization. Multivariate analysis of variance (MANOVA) revealed that High
      Sociable animals had a significantly higher antibody response following
      relocation and immunization compared to Low-Sociable animals. There was no effect
      of timing of the immunization on the immune response. The results confirm that
      personality factors can affect animals' immune responses, and that the dimension
      Sociability may be influential in a male's response to social separation and
      relocation.

PMID- 14582130
TI  - Hormonal changes during the mating and conception seasons of wild northern
      muriquis (Brachyteles arachnoides hypoxanthus).
AB  - We investigated hormonal and behavioral changes in wild male and female northern
      muriquis (Brachyteles arachnoides hypoxanthus) at the Estacao Biologica de
      Caratinga, Minas Gerais, Brazil, during a 6-mo period that encompassed the onset
      of the 1998-1999 mating and conception seasons. Individual females resumed mating
      with the resumption of ovarian cycling, which was not synchronized among them or
      related to their cortisol levels. Females experienced two to seven cycles prior
      to conceiving, and the first conception occurred 2 mo after the onset of the
      group's mating season. There were no differences in female cortisol levels across
      their premating, mating, and conception conditions. Cortisol levels were
      significantly higher in females than in males prior to the conception season,
      consistent with the prediction that energy reserves may be associated with
      breeding readiness in females, but not males, in this species. The sustained
      elevation in male cortisol occurred after the peak in their sexual activity,
      which resulted in the first conception of the year. Male cortisol levels were
      positively correlated between years that were similar in rainfall, but differed
      in the timing of sexual and reproductive events. The timing of cortisol
      elevations in males appears to be generally regulated by environmental cues, but
      is responsive to fine-tuning by social and behavioral cues related to the
      unpredictable timing of reproductive opportunities within their extended mating
      season.

PMID- 14582131
TI  - Flow cytometry of GATA transcription factors.
AB  - BACKGROUND: Although GATA-1 and GATA-2 have been shown to play an important role
      in hematopoiesis, the expression levels of these GATA proteins in the targeted
      cell population of clinical samples have not been studied. We applied flow
      cytometry (FCM) to examine the expression levels of these GATA proteins in the
      selected subpopulation in heterogeneous blood cells. METHODS: Cells were treated
      with a fixing solution and methanol followed by staining with specific antibodies
      to GATA proteins in a permeabilizing solution. Immunofluorescence microscopy and
      Northern blot analysis using GATA-1 and GATA-2 transfected cell lines and various
      leukemic cell lines were used to confirm the specificity of this method.
      Subsequently, the method was applied in two-parameter studies combining GATA
      expression with surface marker expression in clinical samples. RESULTS: The
      positive signals were specifically detected in transfected cells and leukemic
      cell lines by FCM in agreement with the results of Northern blot and
      immunofluorescence microscopy. The expression of these GATA factors in the
      targeted cell population was easily detectable by gating with lineage-specific
      cell surface markers. When the expression of these GATA proteins was examined in
      glycophorin A-positive cells in clinical samples, the level of GATA-1 was
      markedly different among the samples. CONCLUSIONS: This detection system is
      useful to evaluate the relative expression level of each GATA protein in the
      targeted cell population among heterogeneous cells, and the results suggest an
      aberrant expression of GATA factors in hematological diseases.

PMID- 14582132
TI  - Routine use of immunophenotype by flow cytometry in tissues with suspected
      hematological malignancies.
AB  - BACKGROUND: Immunophenotype is an essential parameter in the diagnosis of
      hematological malignancies. Flow cytometry (FCM) is used in the analysis of bone
      marrow or peripheral blood samples but is less frequently used in the evaluation
      of tissue biopsies with suspected hematological malignancies. The aim of this
      study was to analyze the role of FCM in the diagnosis of biopsies from patients
      with a suspected hematological disorder. METHODS: A total of 422 consecutive
      biopsies were studied using standard morphology, immunohistochemistry (IHC), and
      FCM. Results of FCM were obtained in less than 3 h and were interpreted
      independently from morphology and IHC. RESULTS: A strong correlation between
      malignant disease and abnormal pattern of FCM was observed (218 of 250) with the
      exception of Hodgkin disease (P < 0.001). Overall, negative predictive value was
      0.52 and positive predictive value was 1. Light chain restriction was observed in
      182 of 201 B-cell lymphoma and in 0 of 142 non-B-cell disorders by FCM. In
      contrast, light chain pattern could only be evaluated in 38 of 91 cases by IHC.
      FCM allowed a rapid diagnosis of infrequent or high-grade malignancies such as
      histiocytic sarcoma or T-lymphoblastic lymphoma. The addition of FCM in the
      routine study of tissue biopsies facilitates the diagnosis of double pathology in
      five (1%) patients. CONCLUSIONS: FCM is a fast and reliable methodology for
      phenotyping tissue samples, which easily detects infrequent hematological
      malignancies, disease-specific phenotypes and clonality in B-cell lymphomas.
      Moreover, the simultaneous recognition of different cell populations allows the
      diagnosis of composite cell lymphomas, or double pathologies.

PMID- 14582133
TI  - Comparative measurement of spontaneous apoptosis in pediatric acute leukemia by
      different techniques.
AB  - BACKGROUND: To distinguish between subgroups of patients with acute leukemia, the
      rate of spontaneous (culture-induced) apoptosis of leukemic cells was evaluated
      using five methods. METHODS: Leukemic cells (cells) from the bone marrow of
      children with acute lymphoblastic leukemia (ALL, n = 112) and acute myeloid
      leukemia (AML, n = 30) were cultured for 20 h in vitro. The level of apoptosis
      was detected by fluorescent microscopy after staining with acridine orange (AO)
      or by flow cytometry after staining using PI, JC-1, the APO-BRDU kit, or the
      AnnexinV-FITC kit. RESULTS: ALL cells were significantly more sensitive to
      spontaneous apoptosis versus AML cells, as was detected by all methods. The least
      sensitive technique was apoptosis detection by sub-G1-peak/PI-staining. No
      difference in the rate of apoptosis in cells was determined between T- and B
      lineage ALL patients. In patients with B-lineage ALL, strong positive correlation
      existed between the level of cells with loss of mitochondrial membrane potential
      (JC-1), chromatin condensation (AO), and externalization of phosphatidylserine
      (AnnexinV+PI+). The proportion of AnnexinV+PI- cells had no correlative link with
      any other apoptotic cell subpopulation. CONCLUSIONS: We found different
      sensitivities of ALL and AML cells to undergoing spontaneous apoptosis in vitro.
      Detection of the early/intermediate, but not the late stage of apoptosis is of
      preferable for correct assignment of spontaneous apoptosis in pediatric acute
      leukemia.

PMID- 14582134
TI  - Production of intracellular IL-2, TNF-alpha, and IFN-gamma by T cells in B-CLL.
AB  - BACKGROUND: Recent evidence indicates that the slowly expanding population of
      CD5(+) B cells that characterizes B-cell chronic lymphocytic leukemia (B-CLL)
      could be related to defects in the response to cytokine produced by T cells that
      regulate apoptosis. We studied the intracellular expressions of interleukin-2 (IL
      2), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma) in
      T-helper 1 cells (Th1 response) of B-CLL. METHODS: Peripheral blood mononuclear
      cells from 21 healthy individuals and purified T cells from 21 early-stage and 15
      late-stage B-CLL patients were activated with phorbol myristate acetate and
      ionomycin. The Th1 cytoplasmic cytokines were evaluated in CD4(+) and CD8(+) T
      cells by flow cytometry. RESULTS: The percentages of CD4(+) and CD8(+) T cells
      positive for IL-2 were significantly lower in B-CLL patients than in healthy
      individuals (P = 0.030 and 0.049, respectively). No significant differences in
      TNF-alpha or IFN-gamma intracellular expressions were found between patients and
      healthy individuals. TNF-alpha- and IFN-gamma-expressing CD8 T cells were disease
      stage dependent, being significantly higher in late-stage patients (P < 0.001 for
      both cytokines). CONCLUSIONS: Our present observations suggested that Th1
      cytokines may be of major importance in the pathogenesis of B-CLL.

PMID- 14582135
TI  - Pan B-cell markers are not redundant in analysis of chronic lymphocytic leukemia
      (CLL).
AB  - BACKGROUND: The classic immunophenotype for chronic lymphocytic leukemia (CLL) is
      CD19(+), restricted dim surface expression of kappa or lambda light chain,
      CD5(+), CD23(+), dim CD20(+), negative FMC7, and negative CD79b. However, the
      necessity of assaying for all 3 pan B-cell markers (CD20, FMC7, and CD79b) by
      flow cytometry has not been definitively documented for CLL. METHODS: Qualitative
      patterns and semi-quantitative assessment of staining intensity for CD20, FMC7
      and CD79b were performed in 70 cases with a current or prior diagnosis of CLL or
      CLL with increased prolymphocytes leukemia (CLL/PL). The concurrent morphology in
      66 of 70 specimens was classified as typical CLL in 53 cases, CLL/PL in 10 cases,
      and large cell lymphoma in 3 cases. RESULTS: Forty percent of the cases varied
      from the characteristic immunophenotype by having moderate or bright staining of
      CD20 (36%), FMC7 (7%), and/or CD79b (18%). Discrepant qualitative staining
      patterns were found between FMC7 and CD20 (21%), CD20 and CD79b (15%), and CD79b
      and FMC7 (10%). Semiquantitative measurement of staining intensity showed little
      correlation between CD79b and CD20 or FMC7. Moderate correlation was seen between
      CD20 and FMC7. No correlation was observed between morphology and intensity of
      marker expression. CONCLUSIONS: Variable patterns and intensity of staining were
      seen for FMC7, CD20, and CD79b in this cohort of CLL samples. Dim or negative
      staining was most consistently seen for FMC7 (93% of specimens). Although FMC7
      staining intensity was moderately correlated with CD20, CD79b intensity was
      poorly correlated with either CD20 or FMC7, and thus, may provide some
      independent information.

PMID- 14582136
TI  - Automated red blood cell differential analysis on a multi-angle light
      scatter/fluorescence hematology analyzer.
AB  - BACKGROUND: Most hematology analyzers today are capable of performing white blood
      cell differential analysis but only limited red blood cell (RBC) differential
      parameters are available. Because of incomplete morphological information on RBC
      abnormalities, 5-10% of samples in hematology laboratories routinely undergo
      smear review. A more complete automated RBC differential capability is desired.
      METHODS: Abbott CELL DYN 4000 analyzer was modified to perform three-dimensional
      (3D) RBC differential analysis (RBC/diff) on cell-by-cell basis at 488 nm as well
      as at 633 nm. Immature RBCs and all nucleated cells are labeled with a
      fluorescent nuclear stain, prior to RBC/diff using light loss and forward scatter
      (FSC) signal or two FSC signals and a third side scatter signal, projecting the
      cytogram onto a precalibrated 3D surface containing grid lines of volume (V) and
      hemoglobin concentration (HC), to determine the V and HC of a cell. Abnormally
      shaped RBCs (AbnRBC) are quantitated by the distance of each event to the 3D
      surface. A total of 154 normal and 484 clinical samples with various
      hemoglobinopathies have been analyzed. RESULTS: The 3D cytogram and the bivariate
      distribution of V and HC of individual event provided information to extract
      quantitative data on V, HC, schistocytes, and AbnRBC of mature and immature RBCs.
      The accuracy level of the 3D data is difficult to assess because of the
      semiquantitative nature of smear review, the only available reference method.
      CONCLUSIONS: The 3D RBC cytograms provide a wealth of morphologic information
      useful for diagnosis and treatment of patients. With powerful computer programs
      available today, it is evident that the rate of smear review can be significantly
      reduced as a result.

PMID- 14582137
TI  - Measurement of proliferation marker Ki67 in breast tumour FNAs using laser
      scanning cytometry in comparison to conventional immunocytochemistry.
AB  - BACKGROUND: A variety of markers, including Ki67, estrogen receptors (ER), and
      progesterone receptors (PgR), are frequently measured in fine needle aspirates
      from human breast carcinomas. Previously, we demonstrated the use of laser
      scanning cytometry (LSC) for the measurement of Ki67, ER, and PgR in a human
      breast carcinoma cell line, MCF7 (21). In the present study, we investigated the
      expression of Ki67 in breast tumour fine needle aspirates (FNAs) using LSC and
      compared the results to the data obtained using conventional immunocytochemistry
      (ICC). METHODS: A total of 11 sets of cytospins of FNAs taken from breast tumours
      at various stages of tamoxifen treatment were used. For LSC, the cytospins were
      stained for Ki67 with fluorescein using immunofluorescence; the nuclei were
      counterstained with propidium iodide. A parallel set of cytospins was stained
      using horseradish peroxidase and diaminobenzidine and scored manually by
      conventional light microscopy. RESULTS: Values for Ki67 obtained using the LSC
      were generally lower than ICC scores. The changes in Ki67 measured by the LSC
      were almost all parallel to those obtained by manual scoring of
      immunocytochemical stains. CONCLUSIONS: It should be possible to use LSC for the
      routine measurement of Ki67 marker in FNAs from human breast carcinomas.

PMID- 14582138
TI  - Antibodies against human cell receptors, CD36, CD41a, and CD62P crossreact with
      porcine platelets.
AB  - BACKGROUND: A limitation in platelet study has been the availability of platelet
      function-specific membrane receptor antibodies for use in the various animal
      species that are currently used in the study of hemostasis and other phenomena.
      METHODS: Platelets were isolated from human and porcine blood. Resting and
      activated platelets were incubated with antibodies against the human cell surface
      receptors CD36 (clone CB38), CD41a (clone HIP8), CD62P (clone AK4), and CD63
      (clone H5C6). Antibody titration and ligand blocking studies also were performed.
      RESULTS: Binding of anti-CD41a and anti-CD62P were similar for human and porcine
      platelets in percentage of platelets labeled and in number of receptors per cell.
      Binding of anti-CD36 was similar between species, with fewer receptors present in
      porcine cells. Anti-CD63 and anti-CD107a did not bind specifically to porcine
      platelets. CONCLUSION: The anti-CD36, anti-CD41a, and anti-CD62P antibodies
      studied crossreact with porcine platelets and will be useful in the investigation
      of platelet function in porcine models.

PMID- 14582139
TI  - Genome-wide linkage survey for genetic loci that influence the development of
      depressive disorders in families with recurrent, early-onset, major depression.
AB  - In this report, we describe the results of the first genome-wide linkage survey
      for genetic loci that influence the development of unipolar Mood Disorders in 81
      families identified by individuals with Recurrent, Early-Onset, Major Depressive
      Disorder (RE-MDD). Model-free linkage analysis was performed using genotypes for
      392 highly informative polymorphisms with an average spacing of 9 cM. The highest
      maximum LOD score observed, 8.19 (genome-wide adjusted P << 0.0001), occurred for
      Recurrent Major Depressive Disorder (R-MDD) at D2S2321 (205 cM), located 121 kb
      proximal to CREB1. Nineteen chromosomal regions contained linkage peaks that
      reached genome-wide statistical significance (genome-wide adjusted P < 0.05) and
      ten of these were "highly significant" (adjusted P < 0.001). Six of the 19
      linkage peaks were revealed only when the analysis included covariates to control
      for the effects of sex and linkage to CREB1. Sex-specific susceptibility loci
      were common and preferentially affected the vulnerability of women to developing
      unipolar Mood Disorders. Five loci revealed evidence of interaction with the
      CREB1 locus in determining susceptibility (epistasis). A systematic candidate
      gene analysis is presented and potential overlaps of the linkage regions for
      unipolar Mood Disorders with those reported for other psychiatric disorders are
      discussed. The findings suggest that genes whose products participate in cellular
      signaling pathways that converge on CREB, as well as the target genes whose
      expression they regulate, may also harbor alleles that affect the development of
      Mood Disorders and related conditions.

PMID- 14582140
TI  - Association study of a brain-derived neurotrophic-factor genetic polymorphism and
      major depressive disorders, symptomatology, and antidepressant response.
AB  - Preclinical studies have shown that brain-derived neurotrophic factor (BDNF) may
      be involved in both antidepressant action and the pathophysiology of major
      depressive disorder (MDD). The present study tested the hypothesis that the BDNF
      gene Val66Met polymorphism is associated with MDD, its clinical manifestations,
      and antidepressant response. To elucidate a genetic predisposition of MDD, we
      studied BDNF-gene Val66Met polymorphism in 152 MDD patients in 255 normal
      controls. We also examined the association of this polymorphism and fluoxetine
      therapeutic response in 110 MDD patients who received a 4-week fluoxetine
      treatment. No significant differences were demonstrated for the genotype or
      allele frequency of the BDNF polymorphism comparing the MDD and control groups.
      Further, no significant differences were noted comparing the three-genotype
      groups for depressive-cluster symptoms. However, a trend (P = 0.086) to improved
      4-week-fluoxetine antidepressant response was demonstrated for heterozygous
      patients in comparison to homozygous analogs. This finding suggests the BDNF
      polymorphism investigated plays no major role in the pathogenesis of MDD.

PMID- 14582141
TI  - Influence of CLOCK gene polymorphism on circadian mood fluctuation and illness
      recurrence in bipolar depression.
AB  - Recent studies showed that a polymorphism (T to C nucleotide substitution) in the
      3' flanking region of the human CLOCK gene is associated with diurnal preferences
      of human healthy subjects, with higher "eveningness" in subjects carrying at
      least one copy of the C allele. We investigated the possible role of CLOCK gene
      polymorphism in the regulation of diurnal mood fluctuations during a major
      depressive episode. Sample (n = 101) was collected, in the context of previously
      reported trials, among patients affected by bipolar disorder type I, depressive
      episode without psychotic features, free of psychotropic medications. Perceived
      mood levels were assessed three times a day with self-administered visual
      analogue scales. Genotype groups showed no significant difference in diurnal mood
      fluctuations. When stratifying the sample by including only patients with an
      adequate period of observation (duration of illness higher than 5 years, n = 69),
      we post-hoc observed a significantly higher recurrence rate in homozygotes for
      the C variant, which was almost double than that of the other genotype groups.
      This preliminary observation leads to hypothesize a role for the CLOCK gene
      polymorphism in the regulation of long-term illness recurrence in bipolar
      disorder. Given the post-hoc nature of the finding, replication in independent
      samples is necessary to confirm it.

PMID- 14582142
TI  - Significant linkage to chromosome 22q for exploratory eye movement dysfunction in
      schizophrenia.
AB  - A genome-wide scan for a locus responsible for exploratory eye movement (EEM),
      which is quantitative and can be disturbed in association with schizophrenia, was
      performed. A 10-cM resolution genome-wide linkage analysis of the EEM disturbance
      with 358 highly polymorphic microsatellite markers in 38 nuclear families with
      122 members (38 probands, 47 sibs, and 37 parents) including 58 sib-pairs yielded
      the suggestive linkage to the GCT10C10 marker on chromosome 22q11.2 (LOD = 2.48).
      Dense mapping with additional markers around the GCT10C10 marker yielded evidence
      for significant linkage between EEM disturbance and markers D22S429 and D22S310
      on chromosome 22q12.1 (LOD score of 4.63) with suggestive evidence for the
      chromosome region 22q11.2-q12.1. Our findings suggest that a relatively small
      number of loci may control the schizophrenia-related quantitative EEM trait. We
      believe that identifying gene(s) on chromosome 22q associated with the EEM
      phenotype may forward our understanding of the etiology of schizophrenia.

PMID- 14582143
TI  - Polymorphism analysis of HOPA: a candidate gene for schizophrenia.
AB  - HOPA is a 25 kb Xq13 gene that codes for a member of the thyroid receptor co
      activator protein (TRAP) family of nuclear receptor co-activators. In our prior
      research, polymorphisms in the opposite paired (Opa) domain of HOPA have been
      associated with a syndrome of aberrant behavior, most prominently psychosis, and
      hypothyroidism. These Opa domain polymorphisms are intriguing because subsequent
      research has demonstrated that changes in the Opa domain of the C. elegans
      orthologue of HOPA results in altered neurogenesis and release of transcriptional
      suppression. In an effort to determine whether other allelic polymorphisms in
      this gene exist and may potentially contribute to increased susceptibility to
      neuropsychiatric illness, we have performed single stranded conformational
      polymorphism (SSCP) analysis of all 45 exons and each of the two potential
      promoter regions of HOPA using DNA from a panel of patients with psychosis. We
      found a rare promoter polymorphism in an individual with schizoaffective disorder
      and extremely low thyroid stimulating hormone (TSH). The most common exonic
      polymorphism in HOPA is the previously demonstrated HOPA(12 bp) polymorphism.
      Transmission disequilibrium analysis of the HOPA(12 bp) polymorphism showed
      segregation with affected status in six of eight instances. We suggest that this
      evidence supports previous associations of HOPA(12 bp) with a broad range of
      neuropsychiatric illness and conclude that further studies of this uncommon
      polymorphism are merited.

PMID- 14582144
TI  - Comparison of polymorphisms in the alpha7 nicotinic receptor gene and its partial
      duplication in schizophrenic and control subjects.
AB  - The hypothesis that the 15q13-15 region of chromosome 15 contains a gene that
      contributes to the etiology of schizophrenia is supported by multiple genetic
      linkage studies. The alpha7 neuronal nicotinic acetylcholine receptor (CHRNA7)
      gene was selected as the best candidate gene in this region for molecular
      investigation, based on these linkage findings and biological evidence in both
      human and rodent models. CHRNA7 receptors are decreased in expression in
      postmortem brain of schizophrenic subjects. A dinucleotide marker, D15S1360, in
      intron two of the CHRNA7 gene is genetically linked to an auditory gating deficit
      found in schizophrenics and half of the first-degree relatives of patients.
      Single strand conformation polymorphism (SSCP) and sequence analyses of DNA from
      schizophrenic and control individuals identified 33 variants in the coding region
      and intron/exon borders of the CHRNA7 gene and its partial duplication,
      dupCHRNA7; common polymorphisms were mapped. Twenty-one variants were found in
      the exons, but non-synonymous changes were rare. Although the expression of
      CHRNA7 is decreased in schizophrenia, the general structure of the remaining
      receptors is likely to be normal.

PMID- 14582145
TI  - Polymorphism screening of PIP5K2A: a candidate gene for chromosome 10p-linked
      psychiatric disorders.
AB  - Lithium is a potent noncompetitive inhibitor of inositol monophosphatases,
      enzymes involved in phosphoinositide (PI) and inositol phosphate metabolism. A
      critical component of the PI pathway is phosphatidylinositol 4,5-bisphosphate
      (PtdIns(4,5)P(2)), which is hydrolyzed to second messengers and has a direct role
      in synaptic vesicle function. Interestingly, a number of genes involved in the
      synthesis and dephosphorylation of PtdIns(4,5)P(2) are found in regions of the
      genome previously mapped in bipolar disorder (BD) including 10p12, 21q22, and
      22q11, among others. Some of these regions overlap with loci mapped in
      schizophrenia (SZ). One gene involved in PI metabolism that maps to a region of
      interest is 10p12-linked PIP5K2A, a member of the phosphatidylinositol 4
      phosphate 5-kinase family. Polymorphism screening revealed the existence of an
      imperfect CT repeat polymorphism located near the exon 9-intron 9 splice donor
      site. A modest difference was found in the distribution of alleles from this
      highly polymorphic variant when bipolar and schizophrenic subjects were compared
      with controls; relatively rare short repeat variants were found more commonly in
      patients and homozygosity for a common long repeat variant was found more
      commonly in controls. These data suggest that the imperfect CT repeat in PIP5K2A
      intron 9 should be further investigated as a possible candidate allele for 10p12
      linked psychiatric disorders.

PMID- 14582147
TI  - Meta-analysis of the association between the catecholamine-O-methyl-transferase
      gene and obsessive-compulsive disorder.
AB  - Obsessive-compulsive disorder (OCD) is a chronic, severely debilitating mental
      illness that affects approximately 1-2% of the population. Data from twin and
      family studies have shown that genetic factors contribute to the expression of
      the disease. The dopaminergic system has been implicated in the pathogenesis of
      OCD, and catecholamine-O-methyl-transferase (COMT) is a key modulator of
      dopaminergic and noradrenergic neurotransmission. The gene for COMT has a common
      polymorphism that has been shown to be correlated with a three- to fourfold
      change in enzymatic activity. Several groups have searched for an association
      between the COMT gene polymorphism and the presence or absence of OCD, with
      contrasting results. We conducted a systematic review and meta-analysis of both
      the published literature and unpublished data. Available data were stratified
      according to the original study design as either case-control or family-based,
      and two separate meta-analyses were conducted, using both fixed-effects and
      random-effects models. These analyses showed insufficient evidence to support an
      association between the COMT gene polymorphism and OCD. Subgroup stratification
      based on gender generated no statistically significant associations. These
      results should be considered in any future work correlating the COMT gene with
      OCD.

PMID- 14582146
TI  - Candidate gene analysis of the human metabotropic glutamate receptor type 4
      (GRM4) in patients with juvenile myoclonic epilepsy.
AB  - Hereditary factors play a major role in the genetically complex etiology of
      juvenile myoclonic epilepsy (JME). Linkage studies in families of JME probands
      suggest a susceptibility locus (EJM1) for idiopathic generalized epilepsy (IGE)
      in the chromosomal region 6p21.3 near the HLA region. The gene encoding the
      metabotropic glutamate receptor type 4 (GRM4) has been localized within the EJM1
      region and represents a high-ranking candidate gene. Therefore, we have sequenced
      the coding regions and regulatory GRM4 sequences in 20 IGE probands who were
      derived from families of JME probands providing positive linkage evidence to the
      HLA-DQ locus. Our mutation analysis detected three synonymous exonic single
      nucleotide polymorphisms (SNP; exon-7: c.1455T > C, exon-8: c.2002A > G, exon-10:
      c.2733C > T), one SNP in the 3'-untranslated region (c.2890A > G), and two
      intronic SNPs (intron-3: IVS3 + 2732A > G, intron-7: IVS7 + 39C > T). None of the
      identified SNPs was likely to affect receptor function or gene expression. The
      population-based association study did not show significant differences in the
      allele and genotype frequencies of the common c.1455T > C SNP between 144 German
      JME probands and 144 healthy population controls (P > 0.84). Likewise, the family
      based transmission disequilibrium test did not indicate a preferential
      transmission of exon-7 SNP alleles in 31 informative parent-child transmissions
      (P = 0.86). Our results provide no evidence that genetic variation of the GRM4
      gene confers susceptibility to JME-related IGE syndromes.

PMID- 14582148
TI  - [Malignant melanoma of the pelvis as a possible cause of pelvic limb lameness in
      two gray mares].
AB  - Two grey mares, a 12-year-old Arabian and a 13-year-old Lippizaner cross, were
      referred for chronic pelvic limb lameness and abduction of the limb during the
      non supporting phase of the stride. The clinical examination revealed melanomas
      under the tail and on the perineum, and oedema of the proximal lame limb. A mass
      in the pelvic area was detected on rectal palpation. Laparoscopy was performed
      and the provisional diagnosis of malignant melanoma was made. Histological
      examination of the biopsy taken under laparoscopic control from the mass in the
      pelvis confirmed the diagnosis of malignant melanoma. In the postmortem
      examination a large black mass in the pelvis and metastases in several organs
      were diagnosed. The process under the tail showed microscopically the
      characteristics of dermal melanomatosis. The metastases showed the appearance of
      a malignant melanoma. The lameness and abduction during the non supporting phase
      of the stride were possibly caused by a combination of pain, a mechanical
      limitation, and paresis/paralysis. When an older grey horse with melanomas on the
      predilection sites is submitted with pelvic limb lameness and abduction of the
      limb during the non supporting phase of the stride, a malignant melanoma in the
      pelvis is one of the differential diagnoses and a rectal examination should be
      performed. Diagnostic laparoscopy in the standing horse can be useful to confirm
      the provisional diagnosis.

PMID- 14582149
TI  - [Missed diagnosis in rare disease].

PMID- 14582150
TI  - [Review 2001: The veterinary drug legislation is being revised. A brief insight
      into the European Union legislation process concerning drugs].

PMID- 14582151
TI  - ["What do you do these days...?" Veterinarian at work. Interview by Lisetta
      Verkleij].

PMID- 14582152
TI  - [Interview with professor Dr. Cees Wensing, chairman committee for animal
      welfare. "Welfare-unfriendly behavior more ignorance than unwilling." Interview
      by Bert Hendricks].

PMID- 14582153
TI  - [Waiting times, parenteral support and off-label treatment. Gathering of the
      Udder Health Panel].

PMID- 14582154
TI  - [A certified mixed one man practice].

PMID- 14582155
TI  - Chinese hamster cell variants resistant to the A chain of ricin carry altered
      ribosome function.
AB  - Ricin, a toxic lectin from Ricinus communis, is composed of two different
      polypeptide chains, A and B, and the ricin A chain (RA) blocks protein synthesis.
      We studied cell lines resistant to cytotoxic action of RA. One low-RA-resistant
      cell line, AR10, isolated from Chinese hamster ovary (CHO) cells, was resistant
      to a low dose of RA (1 microgram/ml) and showed a 10-fold-higher resistance to RA
      and ricin than that of CHO. We further mutagenized AR10 to isolate high-RA
      resistant cell lines AR100-6, AR100-9, and AR100-13, which were resistant to
      higher doses of RA and ricin (100- to 1,000-fold) than CHO was. The binding of
      [125I]ricin to AR10, AR100-6, AR100-9, and AR100-13 cells was decreased to about
      30% of that of CHO. The internalization of [125I]ricin in AR10 cells and in the
      high-RA-resistant clones was the same. Polyuridylate-dependent polyphenylalanine
      synthesis, using S-30 extracts from either AR100-9 or AR100-13, was about 100
      fold more resistant to the inhibitory action of RA than when CHO, AR10, and AR100
      6 cells extracts were used. The protein synthesis with ribosomes (80S) from AR100
      9 or AR100-13 was 10- to 100-fold more resistant to RA than it was with parental
      ribosomes when combined with the S-100 fraction of CHO cells. The
      polyphenylalanine synthesis assay using the ribosomes constituted from the 60S
      subunit of AR100-9 and the 40S subunit of CHO indicated that the resistant
      phenotype of AR100-9 cells is due to an alteration of the 60S ribosomal subunit.

PMID- 14582156
TI  - Phage particle-mediated gene transfer to cultured mammalian cells.
AB  - Recombinant phage particles carrying the thymidine kinase (TK) gene of herpes
      simplex virus type 1, coprecipitated with calcium phosphate, efficiently
      transformed mouse Ltk- cells to the TK+ phenotype. The conditions necessary to
      achieve high efficiency of transfer of the TK gene by phage particle-mediated
      gene transfer were investigated. Of the parameters examined, the pH of the buffer
      used for coprecipitation of phage particles with calcium phosphate, the length of
      time of coprecipitation, and the length of the adsorption period were found to
      alter the transfer efficiency significantly. The optimal pH was 6.87 at 25
      degrees C. The other optimal values for these parameters were as follows:
      coprecipitation time, 7 to 20 min; adsorption time, 18 to 30 h. Treatment with
      dimethyl sulfoxide, glycerol, or sucrose did not enhance gene transfer. The
      optimal conditions yielded about 1 transformant per 10(5) phage particles per
      10(6) cells without carrier DNA. An increase in the dosage of phage particles, up
      to at least 5 x 10(7) phage particles per 100-mm dish, resulted in a linear
      increase in the number of transformants. Addition of carrier phage, up to 10(10)
      phage particles per dish, did not significantly affect the number of
      transformants.

PMID- 14582158
TI  - Heterogeneity in the rate of benzo[a]pyrene metabolism in single cells:
      quantitation using flow cytometry.
AB  - We describe a method for quantitating heterogeneity in the rate of benzo[a]pyrene
      metabolism in single cells by using flow cytometry. We have used the technique to
      study the response of Hepa-1c1c7 mouse hepatoma cells to the microsomal enzyme
      inducer 2,3,7,8-tetrachlorodibenzo-p-dioxin. Cells responded in a relatively
      homogeneous fashion at different times of induction with a maximally inducing
      concentration of the inducer. However, the induction response could be
      heterogeneous at a submaximal inducer concentration. We found even higher
      heterogeneity of enzyme activity among low-activity variants derived from the
      Hepa-1c1c7 cell line. When cells of either high or low activity were isolated
      from such a clonal population, propagated, and reanalyzed, they displayed average
      enzyme activity and heterogeneity identical to the parental cells; therefore, the
      heterogeneity represents transient, nonheritable differences between cells within
      the population.

PMID- 14582157
TI  - Transcripts from the cellular homologs of retroviral oncogenes: distribution
      among chicken tissues.
AB  - The oncogenes (v-onc genes) of rapidly transforming retroviruses have homologs (c
      onc genes) in the genomes of normal cells. In this study, we characterized and
      quantitated transcription from four c-onc genes, c-myb, c-myc, c-erb, and c-src,
      in a variety of chicken cells and tissues. Electrophoretic analysis of
      polyadenylated RNA, followed by transfer to nitrocellulose and hybridization to
      cloned onc probes showed that c-myb, c-myc, and c-src each give rise to a single
      mature transcript, whereas c-erb gives rise to multiple transcripts (B. Vennstrom
      and J. M. Bishop, Cell, in press) which vary in abundance among different cells
      and tissues. Transcription from c-myb, c-myc, c-erb, and c-src was quantitated by
      a "dot-blot" hybridization assay. We found that c-myc, c-erb, and c-src
      transcription could be detected in nearly all cells and tissues examined, whereas
      c-myb transcription was detected only in some hemopoietic cells; these cells,
      however, belong to several different lineages. Thus, in no case was expression of
      a c-onc gene restricted to a single cell lineage. There appeared to be a
      correlation between levels of c-myb expression and hemopoietic activity of the
      tissues and cells examined, which suggests that c-myb may be expressed primarily
      in immature hemopoietic cells. An examination of c-onc RNA levels in target cells
      and tissues for viruses carrying the corresponding v-onc genes revealed no
      obvious correlation, direct or inverse, between susceptibility to transformation
      by a given v-onc gene and expression of the homologous c-onc gene.

PMID- 14582160
TI  - Identification of phosphotyrosine-containing proteins in untransformed and Rous
      sarcoma virus-transformed chicken embryo fibroblasts.
AB  - Phosphorylation on tyrosine residues mediated by pp60src appears to be a primary
      biochemical event leading to the establishment of the transformed phenotype in
      Rous sarcoma virus (RSV)-infected cells. To identify the cellular proteins that
      undergo tyrosine phosphorylation during transformation, a 32P-labeled RSV
      transformed chicken embryo cell extract was analyzed by electrophoresis on a
      polyacrylamide gel. After slicing the gel into approximately 60 slices,
      phosphoamino acid analyses were carried out on the protein recovered from each
      gel slice. Phosphotyrosine was found in every gel slice, with two major peaks of
      this phosphoamino acid around M(r)'s of 59 and 36 kilodaltons. When the same
      analysis was performed with cells infected with a transformation-defective src
      deletion mutant of RSV (tdNY101), significant and reproducible peaks of
      phosphotyrosine were found in only 2 of 60 gel slices. These gel slices
      corresponded to M(r)'s of 42 and 40 kilodaltons. Identical results were obtained
      with normal uninfected chicken embryo fibroblasts. We conclude from these
      observations that pp60src or the combined action of pp60src and pp60src-activated
      cellular protein kinases cause the tyrosine-specific phosphorylation of a very
      large number of cellular polypeptides in RSV-transformed cells. In addition,
      untransformed cells appear to possess one or more active tyrosine-specific
      protein kinases which are responsible for the phosphorylation of a limited number
      of proteins. These proteins are different from the major phosphotyrosine
      containing proteins of the transformed cells.

PMID- 14582159
TI  - Role of methylation in the induced and spontaneous expression of the avian
      endogenous virus ev-1: DNA structure and gene products.
AB  - The endogenous avian provirus ev-1 is widespread in white leghorn chickens.
      Although it has no major structural defects, ev-1 has not been associated with
      any phenotype and is ordinarily expressed at a very low level. In this report, we
      describe a chicken embryo (Number 1836) cell culture containing both ev-1 and ev
      6 which spontaneously expressed the ev-1 provirus. This culture released a high
      level of noninfectious virions containing a full complement of virion structural
      (gag) proteins but devoid of reverse transcriptase activity or antigen. These
      virions contained 70S RNA closely related to the genome of Rous-associated virus
      type 0, but identifiable as the ev-1 genome by oligonucleotide mapping. A
      fraction of the RNA molecules in the 70S complex were unusual in that they were
      polyadenylated 100 to 200 nucleotides downstream of the usual polyadenylation
      site. Eight sibling embryo cultures did not share this unusual phenotype with
      1836, indicating that it was not inherited. However, an identical phenotype was
      inducible in the sibling cultures by treatment with 5-azacytidine, an inhibitor
      of DNA methylation, and the induced expression was stable for more than 10
      generations. Analysis of chromatin structure and DNA methylation of the ev-1
      provirus in 1836 cells revealed the presence (in a fraction of the proviruses) of
      both DNase I hypersensitive sites in the long terminal repeats and in gag and a
      pattern of cleavage sites for methyl-sensitive restriction endonuclease not found
      in a nonexpressing sibling. These results lend strong support to the role of DNA
      methylation in the control of gene expression. Additionally, they explain the
      lack of phenotype associated with ev-1 as due to a combination of its low
      expression and defectiveness in pol and env.

PMID- 14582161
TI  - DNA-mediated transfer of an RNA polymerase II gene: reversion of the temperature
      sensitive hamster cell cycle mutant TsAF8 by mammalian DNA.
AB  - Treatment of the TsAF8 temperature-sensitive (TS) mutant of Syrian hamster BHK-21
      cells, with calcium phosphate precipitates of genomic TS+ DNAs from a variety of
      mammalian cell lines permitted the selection of TS+ colonies at 40 degrees C. TS+
      transformation events were distinguished from spontaneous TS+ reversions in
      experiments in which alpha-amanitin-sensitive (Amas) TS+ DNA was used to
      transform an AmaR derivative of TsAF8 cells and AmaR TS+ DNA was used to
      transform Amas TsAF8 cells. In each case it was possible to demonstrate the
      unselected acquisition of the appropriate Amas or AmaR phenotype with the
      selected TS+ allele. Each of these TS+ transformed cell lines when grown at 40
      degrees C contained an RNA polymerase II activity with a sensitivity to
      inhibition by alpha-amanitin characteristic of the particular DNA used to
      transform the TS cells, whereas at 34 degrees C the same cells contained a
      mixture of AmaR and Amas polymerase II activities. Together, these data provide
      convincing evidence that the RNA polymerase II gene determining sensitivity to
      inhibition by alpha-amanitin can be transferred to TsAF8 cells and that the TS
      defect in TsAF8 is a polymerase II mutation.

PMID- 14582162
TI  - Human cytoplasmic actin proteins are encoded by a multigene family.
AB  - We characterized nine human actin genes that we isolated (Engel et al., Proc.
      Natl. Acad. Sci. U.S.A. 78:4674-4678, 1981) from a library of cloned human DNA.
      Measurements of the thermal stability of hybrids formed between each cloned actin
      gene and alpha-, beta-, and gamma-actin mRNA demonstrated that only one of the
      clones is most homologous to sarcomeric actin mRNA, whereas the remaining eight
      clones are most homologous to cytoplasmic actin mRNA. By the following criteria
      we show that these nine clones represent nine different actin gene loci rather
      than different alleles or different parts of a single gene: (i) the restriction
      enzyme maps of the coding regions are dissimilar; (ii) each clone contains
      sufficient coding region to encode all or most of an entire actin gene; and (iii)
      each clone contains sequences homologous to both the 5' and 3' ends of the coding
      region of a cloned chicken beta-actin cDNA. We conclude, therefore, that the
      human cytoplasmic actin proteins are encoded by a multigene family.

PMID- 14582163
TI  - Regulation of ribosomal protein mRNA content and translation in growth-stimulated
      mouse fibroblasts.
AB  - When resting (G0) mouse 3T6 fibroblasts are serum stimulated to reenter the cell
      cycle, the rates of synthesis of rRNA and ribosomal proteins increase, resulting
      in an increase in ribosome content beginning about 6 h after stimulation. In this
      study, we monitored the content, metabolism, and translation of ribosomal protein
      mRNA (rp mRNA) in resting, exponentially growing, and serum-stimulated 3T6 cells.
      Cloned cDNAs for seven rp mRNAs were used in DNA-excess filter hybridization
      studies to assay rp mRNA. We found that about 85% of rp mRNA is polyadenylated
      under all growth conditions. The rate of labeling of rp mRNA relative to total
      polyadenylated mRNA changed very little after stimulation. The half-life of rp
      mRNA was about 11 h in resting cells and about 8 h in exponentially growing
      cells, values which are similar to the half-lives of total mRNA in resting and
      growing cells (about 9 h). The content of rp mRNA relative to total mRNA was
      about the same in resting and growing 3T6 cells. Furthermore, the total amount of
      rp mRNA did not begin to increase until about 6 h after stimulation. Since an
      increase in rp mRNA content did not appear to be responsible for the increase in
      ribosomal protein synthesis, we determined the efficiency of translation of rp
      mRNA under different conditions. We found that about 85% of pulse-labeled rp mRNA
      was associated with polysomes in exponentially growing cells. In resting cells,
      however, only about half was associated with polysomes, and about 30% was found
      in the monosomal fraction. The distribution shifted to that found in growing
      cells within 3 h after serum stimulation. Similar results were obtained when
      cells were labeled for 10.5 h. About 70% of total polyadenylated mRNA was in the
      polysome fraction in all growth states regardless of labeling time, indicating
      that the shift in mRNA distribution was species specific. These results indicate
      that the content and metabolism of rp mRNA do not change significantly after
      growth stimulation. The rate of ribosomal protein synthesis appears to be
      controlled during the resting-growing transition by an alteration of the
      efficiency of translation of rp mRNA, possibly at the level of protein synthesis
      initiation.

PMID- 14582164
TI  - Nuclear inheritance of erythromycin resistance in human cells: new class of
      mitochondrial protein synthesis mutants.
AB  - The characterization of two new erythromycin-resistant mutants of HeLa cells is
      described. The strains ERY2305 and ERY2309 both exhibited resistance to
      erythromycin in growth assays and cell-free mitochondrial protein synthesis
      assays. The erythromycin resistance phenotype could not be transferred by
      cybridization. The mutation appeared to be encoded in the nucleus and inherited
      as a recessive trait. These two mutants, therefore, represent a new class of
      erythromycin-resistant mutants in human cells that is distinct from the
      cytoplasmically inherited mutation in strain ERY2301 described previously.

PMID- 14582165
TI  - Further evidence that the majority of primary nuclear RNA transcripts in
      mammalian cells do not contribute to mRNA.
AB  - Nuclear RNA from Chinese hamster ovary cells was effectively separated into
      polyadenylic acid [poly(A)]-containing [poly (A)+] and non-poly(A)-containing
      [poly(A)-] fractions so that -90% of the poly(A) was present in the (A)+
      fraction. Only 25% of the 5'-terminal caps of the large nuclear molecules were
      present in the (A)+ class, but about 70% of the specific mRNA sequences (assayed
      with cDNA clones) were in the (A)+ class. It appears that many long capped
      heterogeneous nuclear RNA molecules are of a different sequence category from
      those molecules that are successfully processed into mRNA.

PMID- 14582166
TI  - Phenotypic switching in cells transformed with the herpes simplex virus thymidine
      kinase gene.
AB  - Biochemical transformation of Ltk- cells with the herpes simplex virus thymidine
      kinase (tk) gene resulted in numerous TK+ colonies that survived selection in
      hypoxanthine-aminopterin-thymidine medium. Many of these TK+ cell lines switched
      phenotypes and reverted to the TK- state. In this report, we describe the
      biological and biochemical characteristics of three TK- revertant lines. One
      (K1B5) transiently expressed TK in the presence of bromodeoxyuridine, which
      selects for the TK- phenotype. Another TK- sibling (K1B6n) expressed TK only
      after removal from bromodeoxyuridine-containing medium. The last variant (K1B6me)
      lost the ability to switch to the TK+ phenotype, although it maintained the
      herpes simplex virus sequences coding for TK. Loss of the ability of K1B6me cells
      to express TK was correlated with extensive methylation of the sequence
      recognized by the restriction endonuclease HpaII (pCpCpGpG). After these cells
      were treated with 5-azacytidine, they regained the ability to clone in
      hypoxanthine-aminopterin-thymidine medium and reexpressed virus tk mRNA and
      enzyme. In addition, the HpaII sites that were previously shown to be refractile
      to enzyme digestion were converted to a sensitive state, demonstrating that they
      were no longer methylated.

PMID- 14582167
TI  - Effects of chloramphenicol on the mitochondrial respiratory chain in the wild
      strain and in a cytoplasmic chloramphenicol-resistant mutant of Tetrahymena
      pyriformis.
AB  - The effects of chloramphenicol (CAP) on mitochondrial respiratory activity in the
      wild strain (ST) and in a cytoplasmic CAP-resistant mutant (STR1) of Tetrahymena
      pyriformis were studied by determining oxygen consumption, by spectrophotometry,
      and by cytochemistry. In the absence of CAP both strains had the same respiration
      capacity, and the low-temperature spectra of their isolated mitochondria were
      similar. Furthermore, the mitochondria of both strains showed a positive reaction
      with diaminobenzidine, denoting a similar cytochrome oxidase activity. However,
      when cells were grown in CAP for 24 or 48 h, the peaks of cytochrome oxidase and
      cytochromb b were almost absent in the wild type. In this type the oxygen
      consumption was greatly decreased, and the mitochondria were no longer stained by
      diaminobenzidine. In the mutant, the peaks of cytochrome oxidase and cytochrome b
      were decreased only; respiration was less affected than in the wild type, and
      cytochrome oxidase activity was still disclosed by the diaminobenzidine reaction.
      These results show that CAP inhibits the synthesis of two cytochromes (b and
      oxidase) which are partially translated into the mitochrondria of T. pyriformis.
      In the mutant, CAP reduces only the mitochondrial translation, resulting in
      reduced mitochondrial activity and reduced growth rate of the cell. These results
      are compared with the nucleo-mitochondrial regulation mechanisms discussed in our
      previous works.

PMID- 14582168
TI  - Revertants of a Chinese hamster ovary cell mutant with an altered beta-tubulin:
      evidence that the altered tubulin confers both colcemid resistance and
      temperature sensitivity on the cell.
AB  - We recently described the isolation of a mutant Chinese hamster ovary cell (Cmd
      4) resistant to the cytotoxic effects of colcemid (Cabral et al., Cell 20:29-36,
      1980). This mutant carries an altered beta-tubulin but still grows normally at 37
      degrees C. In the present study we found that Cmd 4 is temperature sensitive for
      growth at 40.3 degrees C. A class of revertants selected for temperature
      resistance had simultaneously lost colcemid resistance and the altered beta
      tubulin. In addition, we isolated a temperature-resistant revertant which carries
      a further alteration in the mutant beta-tubulin polypeptide. This second
      alteration appears to make the mutant beta-tubulin incompetent to assemble into
      microtubules, resulting in a strain which is again colcemid sensitive. These
      revertant cell lines provide strong evidence that a mutation in beta-tubulin can
      confer both colcemid resistance and temperature sensitivity on a mammalian cell
      line. Cellular microtubules studied by indirect immunofluorescence in both mutant
      and revertant cell lines had an apparently normal distribution at permissive and
      nonpermissive temperatures, yet mitosis appears to be abnormal in the mutant cell
      line. We conclude from these studies that incorporation of the altered beta
      tubulin into microtubules does not affect their distribution but may affect their
      function during mitosis.

PMID- 14582169
TI  - The future of kidney preservation.
AB  - Both methods of hypothermic preservation of kidneys currently used clinically
      have been and continue to be useful procedures for the transplant surgeon. Each
      method has its limitations, benefits, and potential detriments. Which method is
      best is not a fully resolved question and the method of choice appears to be
      dependent upon, to a large extent, personal preference and circumstances. There
      is, however, a vital need for long-term kidney preservation. Obtaining this goal
      will most likely require carefully controlled experimental studies linking the
      biochemical and physiological aspects of organ metabolism at hypothermia to the
      design of perfusates, perfusion machine technology, and drug therapy.
      Improvements in perfusion preservation methodology based on sound basic data
      rather than by serendipity appears to offer the best opportunity for obtaining
      good quality long-term preservation.

PMID- 14582170
TI  - Renal preservation prior to transplantation.

PMID- 14582171
TI  - Immunosuppressive properties of rabbit antibodies against a major glycoprotein
      restricted to rat leukocyte membranes.
AB  - The role of antibodies to the rat leukocyte-common (LC) antigen in the
      immunosuppression induced by antilymphocyte serum (ALS) was tested in two ways.
      First, two batches of rabbit antisera to purified rat LC antigen and a
      conventional rabbit anti-rat thoracic duct lymphocyte serum (ALS) were compared
      for their ability to suppress the rejection of LEW (RT1l) kidney grafts
      transplanted to DA (RT1a) recipients. All three sera were able to suppress
      rejection completely. However, when the amount of lymphocyte-binding
      immunoglobulin necessary for effective immunosuppression was compared, the anti
      LC sera were found to be 10-fold weaker than the conventional ALS. In the second
      experiment the conventional ALS was depleted of its anti-LC antibodies by
      incubating with pure LC antigen, and this was found not to diminish its
      immunosuppressive potency. It was concluded that anti-LC antibodies do not
      contribute significantly to the immunosuppressive potency of conventional ALS.
      This is despite the fact that anti-LC antibodies constituted 48% of the
      antibodies in the ALS used in the immunosuppression experiments, and in six other
      batches of ALS the proportion of anti-LC antibodies ranged from 25 to 49%.
      Because only a small component of the nonanti-LC antibodies are directed at
      leukocyte-specific antigens, it is concluded that the immunosuppressive
      properties of ALS are mediated by a minor component of the serum directed at as
      yet undefined antigens. In additional experiments, a mouse monoclonal antibody to
      the rat LC antigen, a mouse monoclonal antibody (W3/13) to a rat T lymphocyte
      brain-granulocyte antigen, and rabbit antisera to pure rat Thy-1 were tested for
      their ability to suppress kidney graft rejection, but none had any effect at all,
      even in large doses.

PMID- 14582172
TI  - Modulation of tissue immunogenicity by organ culture. Comparison of adult islets
      and fetal pancreas.
AB  - Uncultured mouse islet allografts (BALB/c to CBA) are rejected 2 to 4 weeks after
      transplantation. Allografts, cultured in 95% O2 and 5% CO2 for 7 days before
      transplantation, show no sign of rejection up to 3 months post-transplantation.
      However, the cultured allografts are rejected if the CBA recipient is given an
      i.v. injection of 10(5) peritoneal cells at the time of transplantation. Organ
      culture of BALB/c fetal pancreas (16 to 17 days gestation) under the same
      conditions failed to prevent allograft rejection. The immunogenicity of fetal
      pancreas is reduced if this tissue is cultured in 95% O2 and 5% CO2 for 17 days
      before transplantation.

PMID- 14582173
TI  - Male skin isografts can induce unresponsiveness in female rats.
AB  - Nonsensitized (DA x PVG/c) F1 hybrid female rats regularly accepted male skin
      isografts. However, almost all F1 females sensitized with male F1 bone marrow
      cells rejected male skin isografts. Spleen cells taken from sensitized F1
      females, either before or after the rejection of male skin isografts, conferred
      resistance against graft-versus-host (GVH) reactions produced in F1 females by
      parental PVG/c lymph node cells, but only when the cell donors were male.
      Repeated injection with bone marrow cells from F1 males failed to cause rejection
      of established male skin grafts by F1 females. Additional male skin grafts
      transferred after bone marrow cell injection were also retained. However, if
      established male skin isografts had been deliberately removed from F1 females
      before injection of male bone marrow cells, subsequently placed male skin grafts
      were rejected. Neither spleen cells collected from F1 females bearing established
      male skin isografts after repeated injection with male bone marrow cells, nor
      spleen cells obtained from F1 females that had received four consecutive male
      skin isografts were observed to confer resistance against GVH reactions produced
      by male PVG/c lymph node cells in F1 female recipients. Splenectomy of
      prospective F1 female recipients did not confer on them the capacity to reject
      male skin isografts. These results imply that the placement of a male skin
      isograft interfered with subsequent attempts to stimulate F1 hybrid females to
      reject male grafts and to resist GVH reactions produced by lymphocytes from PVG/c
      males.

PMID- 14582174
TI  - Genetics of teratocarcinoma transplantation. II. Effect of a semidominant H-2
      linked gene lying outside the immediate major histocompatibility complex on tumor
      formation by the embryonal carcinoma cell line F9 in H-2 congenic pairs.
AB  - H-2 substitutions on the B6 and AKR backgrounds have been found to decrease
      allograft resistance to the embryonal carcinoma cell line F9. (C57BL/6 x B6.AK-H
      2k)F1 and (C57BL/6 x AKR.B6-H-2b)F1 animals show resistance intermediate to that
      of the respective parental strains and this result, along with that from F2
      analyses, suggests that the resistance differential in each congenic pair is
      under the control of a single semidominant locus. In the C57BL/6 congenic pair,
      the locus has been shown to lie outside of the H-2, Qua2/3, PGK-2 region of the
      17th chromosome.

PMID- 14582175
TI  - Genetics of kidney allograft survival in dogs. III. Relevance of
      histocompatibility matching in immunosuppressed recipients.
AB  - The relevance of matching for the serologically defined (SD) and lymphocyte
      defined (LD) antigens of the major histocompatibility complex (MHC) for renal
      allograft survival was evaluated in a dog model. Kidney recipients were treated
      with a standard regimen of immunosuppressive drugs (azathioprine, 2 mg/kg body
      wt, and prednisolone, 1 mg/kg body wt, daily i.v.) after transplantation. In
      seven of the eight SD- and LD-identical beagle littermate donor-recipient pairs
      (DRPs), and in all seven SD- and LD-identical beagle nonlittermate DRPs, kidney
      function remained normal for the period of 150 days during which
      immunosuppressants were given. Of the 8 beagle littermate DRPs differing in one
      haplotype and all 25 unrelated mismatched mongrel DRPs, kidney function
      deteriorated during immunosuppressive therapy, and most of the recipients died
      eventually from graft rejection. Thus, it seems that, in moderately
      immunosuppressive dogs, non-DLA incompatibilities rarely, if ever, cause
      rejection, whereas DLA incompatibilities almost always do so. The data differ
      from those obtained in a previous study in nonimmunosuppressed dogs, in which non
      DLA incompatibilities seemed to be as strong as DLA incompatibilities in this
      respect. Differences in minor histocompatibility antigens can apparently be
      overcome more easily by immunosuppressive drug therapy than differences in major
      histocompatibility antigens. After the gradual complete withdrawal of
      immunosuppression, 11 of the 15 matched littermate and nonlittermate DRPs
      survived for another 150 days or more, implying that some kind of
      unresponsiveness was induced in those dogs.

PMID- 14582176
TI  - Major histocompatibility complex matching and other factors influencing skin
      allograft survival in related and unrelated rhesus monkeys.
AB  - Skin allografting was performed in rhesus monkeys to study the influence of
      matching for products of the RhLA region and of various other parameters. As
      expected, the longest mean survival times (MSTs) were observed when donors were
      RhLA-identical siblings; the MST seemed a bit shorter when grafts from at least
      two RhLA-nonidentical siblings were simultaneously present. Matching for RhLA-A
      and B locus antigens was studied in RhLA-haploidentical and in unrelated
      combinations; in both categories, the MST was about 12 days if there were no A or
      B antigen disparities, 10 days if there was one A or B disparity, and about 9
      days for two or more disparities. A positive effect of matching for D/DR antigens
      and mixed lymphocyte culture (MLC) nonresponsiveness between host and donor was
      questionable; additional data are required to confirm the minor beneficial effect
      observed. With regard to the sex of donors and recipients, female recipients
      rejected skin allografts more rapidly than did males in related and unrelated
      combinations. In this respect, females with a known or possible history of
      pregnancy were not different from nulliparous animals. A possible influence of
      donor sex on skin allograft survival remained equivocal. The i.v. administration
      of donor-specific antigen before skin grafting led to a significant prolongation
      of the MST; in the majority of combinations with prolonged graft survival, B cell
      specific antibodies were demonstrable in the recipients' sera. An "enhancing"
      influence of such antibodies is possible, although the available data do not
      prove such an effect.

PMID- 14582177
TI  - Equine leukocyte antigen system. I. Serological studies.
AB  - Lymphocytotoxic alloantibodies have been recognized in primiparous mare sera and
      colostra using the two-step microcytotoxicity test. The antigens detected on the
      leukocyte membrane do not occur on the erythrocytes. After testing on a cell
      panel from unrelated horses, absorptions with leukocytes were carried out. The
      subsequent retesting of the serum reagents on a cell panel including cells from
      24 families rendered possible a grouping of preliminary monospecific reagents
      characterizing 18 antigen specificities on the cell membrane.

PMID- 14582178
TI  - Equine leukocyte antigen system. II. Serological and mixed lymphocyte reactivity
      studies in families.
AB  - Mono- and oligospecific lymphocytotoxic alloantibodies from primiparous mares
      were tested on cells from horse families of various breeds in the two-step
      microcytotoxicity assay. The results showed that the detected antigens were
      inherited co-dominantly and autosomally as simple Mendelian traits. The membrane
      antigens showed different linkage with one or more other antigens and seem to be
      coded by a limited number of loci (at least three) from one chromosome. In the
      families tested one recombinant for the serologically defined antigens was
      recognized. The mixed leukocyte reactions of cells from horse families compared
      with the serologically recognized antigens showed that the two systems are
      inherited with the same chromosome. A homozygote for both antigen systems was
      recognized in a family.

PMID- 14582179
TI  - Cardiac allograft rejection and enhancement in natural recombinant rat strains.
AB  - Cardiac allografts were carried out using rat strain combinations with
      recombinant haplotypes. Rejection times were determined in unsensitized
      recipients, recipients that had been immunized to produce hyperacute or
      accelerated rejection, and recipients that had been i.v. immunized with 10(7)
      bone marrow cells to produce active enhancement. The graft survival results
      obtained suggest that there is a major influence of the A region or classical
      type I transplantation antigens in first set and hyperacute rejection whereas
      immunization to both A or B region (Ia) antigens may produce markedly prolonged
      survival. These data suggest major differential influences of major
      histocompatibility complex (MHC) subregions depending on the specific donor
      recipient incompatibility as well as suggesting major influences in these three
      allograft models depending on the background of the strain used.

PMID- 14582181
TI  - Prolongation of cat to dog renal xenograft survival with prostacyclin.

PMID- 14582180
TI  - Effects of protein-calorie restriction on the immune response to skin allografts
      in the rat.
AB  - The effect of protein depletion on immune responsiveness was examined using a
      skin allograft model. Protein depletion was induced in adult Fischer (F344) male
      rats by the ad libitum provision of a 5% protein diet. Total serum protein, total
      body weight, total body nitrogen, and total body lipid were all markedly
      decreased in these rats. Skin from control-fed Brown Norway (BN) male rats was
      grafted to the middorsal region of control and protein-depleted F344 rats. BN
      skin allografts survived significantly longer on protein-depleted recipients
      (13.3 days) than on controls (8.5 days). Splenic lymphoid cells from skin grafted
      F344 rats were assayed for cytotoxicity against BN and F344 lymphoid cells in a
      51Cr release assay. At effector to target ratios of 50:, 100:, and 200:1, spleen
      cells from control rats exhibited greater than 35% allospecific cytotoxicity 8
      days after grafting. Spleen cells from protein-depleted rats exhibited no greater
      than 10% cytotoxicity from 6 to 15 days after grafting. A depression of
      cytotoxicity by protein depletion was also observed in rats immunized by i.p.
      injection of BN spleen cells. Heat-inactivated sera from skin grafted F344 rats
      were assayed against BN and F344 lymphoid cells in a complement-dependent trypan
      blue exclusion assay. Cytotoxic alloantibodies were measurable in both control
      and protein-depleted rats 9 days after grafting, but were of significantly lower
      titer in the protein-depleted group. The results indicate that both humoral and
      cell-mediated immune responses to alloantigens are impaired by protein-calorie
      malnutrition.

PMID- 14582182
TI  - Effect of cyclosporin A upon the function of ischemically damaged renal
      autografts in the dog.

PMID- 14582183
TI  - Esterase D: polymorphic red blood cell enzyme in the dog.

PMID- 14582184
TI  - Effect of in vitro glucose concentration on fetal mouse pancreas cultures used as
      grafts in syngeneic diabetic mice.

PMID- 14582185
TI  - Heterologous interaction between beta 2-microglobulin and Ag-B antigens.

PMID- 14582186
TI  - Effect of donor pretreatment in rats on the antibody response after renal and
      cardiac allografting.

PMID- 14582187
TI  - Normal immunosuppressive protein. Immunoregulation and serum factors.

PMID- 14582189
TI  - Initial characterization of a spontaneous interferon secreted during growth and
      differentiation of Friend erythroleukemia cells.
AB  - A gradual increase in the level of 2',5'-oligoadenylate synthetase takes place in
      Friend erythroleukemia cells after a shiftdown in the rate of cell growth. The
      increase is about 5-fold after entry of cells into the stationary phase of
      growth, but much higher (25-fold) when reduction in growth accompanies cell
      differentiation. In the latter case, the enzyme increase is similar to that which
      can be induced in these cells by exogenous interferon (IFN). The increase in
      2',5'-oligoadenylate synthetase was shown to be due to a spontaneous secretion of
      IFN by the cells themselves: it is completely abolished if antiserum to murine
      type I IFN is added to the culture medium. In attempts to isolate some of this
      spontaneously secreted IFN, we show that it is stable at pH 2, not neutralized by
      antiserum to type II IFN, and that it also differs from the known IFN species
      induced by Sendai virus in Friend cells. The major component of this
      spontaneously secreted IFN is 20,000 M(r) and differs from the corresponding
      virus-induced 20,000-M(r) IFN by its lower affinity for antiserum to type I IFN
      and its antigenic characterization as beta-murine IFN. The major component of the
      spontaneous IFN also exhibits a higher ratio of antigrowth to antiviral activity
      than the Sendai-induced IFNs. We suggest that Friend cells produce this specific
      type of IFN for the regulation of their growth and differentiation.

PMID- 14582188
TI  - New properties of simian virus 40 large T antigen.
AB  - An 8,000-molecular-weight (8K) T antigen was found in all cells transformed by
      simian virus 40. The 8K T antigen was weakly labeled in vivo with [35S]methionine
      or 32Pi. A deletion in the human papovavirus BK genome, in the region coding for
      the carboxy-terminal end of the large T antigen, reduced the size of the 8K T
      antigen. The last 80 amino acids of the large T antigen include the sequence Asp
      Asp-Asp-Asp unique to the activation peptide of trypsinogen. Large T antigen
      bound diisopropyl fluorophosphate and was retained by D-phenylalanine coupled to
      Sepharose beads, an affinity adsorbent that can retain chymotrypsin. The large T
      antigen and the recA protein of Escherichia coli, a known protease, have several
      properties in common as well as several similar sequences. Antibodies against
      large T antigen interacted with native recA protein.

PMID- 14582190
TI  - Properties and possible functions of the adenylate cyclase in plasma membranes of
      Saccharomyces cerevisiae.
AB  - We have examined the possible role of adenosine 3',5'-phosphate (cAMP) in
      functions associated with the plasma membranes of Saccharomyces cerevisiae.
      Purified membranes from this source contained an adenylate cyclase which was
      insensitive to activation by fluoride or guanine nucleotides, only weakly
      responsive to changes of carbon source in the growth medium, and strongly
      stimulated by vanadate. They also contained at least two classes of receptor
      proteins for guanine nucleotides (as measured by binding of labeled 5'-guanylyl
      methylene diphosphate) with apparent dissociation constants equal to 1.0 x 10(-7)
      and 3 x 10(-6) M, a protein kinase capable of phosphorylating added histones, the
      activity of which was stimulated by cAMP, and cAMP receptors that may function as
      regulatory subunits for this kinase. Membrane proteins were also susceptible to
      phosphorylation by endogenous kinase(s), with polypeptides of apparent molecular
      weights equal to 160 x 10(3), 135 x 10(3), 114 x 10(3), and 58 x 10(3) as the
      major targets. Of these, the 114,000-molecular-weight polypeptide was probably
      identical to the proton-translocating ATPase of the membranes. However, the cAMP
      dependent protein kinase did not appear to be involved in these reactions. Intact
      (rho+ or rho0) cells responded to dissipation of the proton electrochemical
      gradient across their plasma membranes by rapid and transient changes in their
      intracellular level of cAMP, as suggested earlier (J. M. Trevillyan and M. L.
      Pall, J. Bacteriol., 138:397-403, 1979). Thus, although yeast plasma membranes
      contain all the essential components of a stimulus-responsive adenylate cyclase
      system, the precise nature of the coupling device and the targets involved remain
      to be established.

PMID- 14582192
TI  - Mutations at the Saccharomyces cerevisiae SUP4 tRNA(Tyr) locus: isolation,
      genetic fine-structure mapping, and correlation with physical structure.
AB  - The SUP4 tRNA(Tyr) locus in Saccharomyces cerevisiae has been studied by the
      isolation and characterization of mutations at the SUP4 gene which result in the
      loss of suppressor function. Most of the mutations act as single-site mutations,
      whereas about a third of the mutations are deletions of the entire gene. Two
      meiotic fine-structure maps of the gene were made. The first mapping technique
      placed 10 mutations plus the sup4+ anticodon on a map by a measurement of levels
      of recombination between pairs of mutations. The second map utilized a more
      qualitative estimate of recombination frequency, allowing 69 mutations and the
      sup4+ anticodon to be mapped. The maps were compared with the physical structure
      of the gene for the 34 mutations whose nucleotide alteration has been determined
      by DNA sequencing (Koski et al., Cell 22:415-425, 1980; Kurjan et al., Cell
      20:701-709, 1980). Both maps show a good correlation with the physical structure
      of the gene, even though certain properties of genetic fine-structure maps, such
      as marker effects and "map expansion," were seen.

PMID- 14582191
TI  - Inhibition of adenovirus DNA synthesis in vitro by sera from patients with
      systemic lupus erythematosus.
AB  - Sera containing antinuclear antibodies from patients with systemic lupus
      erythematosus (SLE) and related disorders were tested for their effect on the
      synthesis of adenovirus (Ad) DNA in an in vitro replication system. After being
      heated at 60 degrees C for 1 h, some sera from patients with SLE inhibited Ad DNA
      synthesis by 60 to 100%. Antibodies to double-stranded DNA were present in 15 of
      the 16 inhibitory sera, and inhibitory activity copurified with anti-double
      stranded DNA in the immunoglobulin G fraction. These SLE sera did not inhibit the
      DNA polymerases alpha, beta, gamma and had no antibody to the 72,000-dalton DNA
      binding protein necessary for Ad DNA synthesis. The presence of antibodies to
      single-stranded DNA and a variety of saline-extractable antigens (Sm, Ha, nRNP,
      and rRNP) did not correlate with SLE serum inhibitory activity. Methods
      previously developed for studying the individual steps in Ad DNA replication were
      used to determine the site of inhibition by the SLE sera that contained antibody
      to double-stranded DNA. Concentrations of the SLE inhibitor that decreased the
      elongation of Ad DNA by greater than 85% had no effect on either the initiation
      of Ad DNA synthesis or the polymerization of the first 26 deoxyribonucleotides.

PMID- 14582193
TI  - Isolation of the CAR1 gene from Saccharomyces cerevisiae and analysis of its
      expression.
AB  - We isolated the CAR1 gene from Saccharomyces cerevisiae on a recombinant plasmid
      and localized it to a 1.58-kilobase DNA fragment. The cloned gene was used as a
      probe to analyze polyadenylated RNA derived from wild-type and mutant cells grown
      in the presence and absence of an inducer. Wild-type cells grown without the
      inducer contained very little polyadenylated RNA capable of hybridizing to the
      isolated CAR1 gene. A 1.25-kilobase CAR1-specific RNA species was markedly
      increased, however, in wild-type cells grown in the presence of inducer and in
      constitutive, regulatory mutants grown without it. No CAR1-specific RNA was
      observed when one class of constitutive mutant was grown in medium containing a
      good nitrogen source, such as asparagine. Two other mutants previously shown to
      be resistant to nitrogen repression contained large quantities of CAR1 RNA
      regardless of the nitrogen source in the medium. These data point to a
      qualitative correlation between the steady-state levels of CAR1-specific,
      polyadenylated RNA and the degree of arginase induction and repression observed
      in the wild type and in strains believed to carry regulatory mutations.
      Therefore, they remain consistent with our earlier suggestion that arginase
      production is probably controlled at the level of gene expression.

PMID- 14582194
TI  - Silkworm 5S RNA and alanine tRNA genes share highly conserved 5' flanking and
      coding sequences.
AB  - A fragment of Bombyx mori genomic DNA containing one tRNA2Ala gene and one 5S RNA
      gene has been used to compare the structural features of silkworm 5S RNA and tRNA
      genes. The nucleotide sequences of both genes and of the primary transcripts
      produced from them in homologous in vitro transcription systems have been
      determined. Comparison of the sequences of these two genes with that of another
      previously analyzed B. mori tRNA2Ala gene reveals common oligonucleotides which
      may be important transcriptional signals. The oligonucleotides TA(C)TAT, AATTTT,
      and TTC are located approximately (+/- 1 nucleotide) 29, 19, and 3 nucleotides,
      respectively, before the transcription initiation sites of the two tRNA2Ala genes
      and the one 5S RNA gene we have analyzed. The sequence GGGCGTAG(C)TCAG lies
      within the coding regions of all three genes. The functional significance of
      these sequences is suggested by their location within regions required for the
      transcription of silkworm alanine tRNA genes in vitro.

PMID- 14582195
TI  - Identification of proteins whose synthesis is modulated during the cell cycle of
      Saccharomyces cerevisiae.
AB  - We examined the synthesis and turnover of individual proteins in the
      Saccharomyces cerevisiae cell cycle. Proteins were pulse-labeled with radioactive
      isotope (35S or 14C) in cells at discrete cycle stages and then resolved on two
      dimensional gels and analyzed by a semiautomatic procedure for quantitating gel
      electropherogram-autoradiographs. The cells were obtained by one of three
      methods: (i) isolation of synchronous subpopulations of growing cells by zonal
      centrifugation.; (ii) fractionation of pulse-labeled steady-state cultures
      according to cell age; and (iii) synchronization of cells with the mating
      pheromone, alpha-factor. In confirmation of previous studies, we found that the
      histones H4, H2A, and H2B were synthesized almost exclusively in the late G1 and
      early S phases. In addition, we identified eight proteins whose rates of
      synthesis were modulated in the cell cycle, and nine proteins (of which five,
      which may well be related, were unstable, with half-lives of 10 to 15 min) that
      might be regulated in the cell cycle by periodic synthesis, modification, or
      degradation. Based on the time of maximal labeling in the cell cycle and on
      experiments with alpha-factor and hydroxyurea, we assigned the cell cycle
      proteins to two classes: proteins in class I were labeled principally in early G1
      phase and at a late stage of the cycle, whereas those in class II were primarily
      synthesized at times ranging from late G1 to mid S phase. At least one major
      control point for the cell cycle proteins occurred between "start" and early S
      phase. A set of stress-responsive proteins was also identified and analyzed. The
      rates of synthesis of these proteins were affected by certain perturbations that
      resulted during selection of synchronous cell populations and by heat shock.

PMID- 14582196
TI  - Genetic test for involvement of intervening sequences in transport of nuclear
      RNA.
AB  - The construction of a recombinant virus in the late region of simian virus 40 is
      presented. The small intervening sequence of late 19S RNA (0.760 to 0.765 map
      unit) was cloned and inserted into the EcoRI site (1.0 map unit) in the late
      region of simian virus 40. This is a mutant virus that now has two intervening
      sequences, one at the normal position (0.760 map unit) and another out of the
      context of its flanking sequence and now at 1.0 map unit. The recombinant appears
      poisonous, as repeated attempts to plaque it as a virus with a standard helper
      virus were unsuccessful. The transcription of this recombinant was, therefore,
      studied after direct DNA transfection onto CV-1 cells. Nuclease S1 analysis of
      mutant RNA indicates that the major nuclear transcript was a spliced but nuclear
      16S RNA species. Normally, 16S RNA is not found in the nucleus. This result was
      shown to be an artifact of the DNA transfection protocol. When the glycerol shock
      was done after infection with virus, a similar alteration in the makeup of
      nuclear RNA was seen. A transient stock of this double-intron mutant was finally
      obtained, using a nonrevertable helper virus. The transcriptional analysis of
      this mutant showed that unspliced 19S RNA was not transported and remained within
      the nucleus, whereas spliced 19S and 16S RNAs were transported. We conclude that
      the retention of nuclear transcripts within the nucleus is not simply due to the
      presence of intronic sequences, as spliced 19S and 16S RNAs which contain the
      second intron were efficiently transported.

PMID- 14582197
TI  - Temperature-sensitive Chinese hamster fibroblast mutant with a defect in RNA
      metabolism.
AB  - We describe a new temperature-sensitive mutant of Chinese hamster cell
      fibroblasts. After a shift to the nonpermissive temperature of 40.5 degrees C,
      the rates of DNA, RNA, and protein synthesis declined rapidly (to < or = 50%
      within 12 h) and the progression of unsynchronized cells through the cell cycle
      was affected. We believe that DNA synthesis came to a halt after a short time,
      because cells no longer entered the S phase. The decrease in protein synthesis at
      40.5 degrees C was shown to be a consequence of a decrease in the number of
      polysomes, whereas free 80S ribosomes accumulated. We concluded that the
      components of the protein biosynthetic machinery were intact (ribosomes and
      soluble factors), but synthesis was limited by a shortage of mRNA. The decline in
      mRNA production had a significant effect on the synthesis of proteins (e.g., heat
      shock proteins) translated from short-lived messages. We observed that both
      polyadenylated and nonpolyadenylated RNA syntheses declined at 40.5 degrees C,
      whereas the synthesis of small RNAs (4 to 5S) was less reduced. The argument is
      made that the temperature-sensitive phenotype is the result of a defect affecting
      mRNA synthesis.

PMID- 14582198
TI  - In vitro methylation of the BsuRI (5'-GGCC-3') sites in the E2a region of
      adenovirus type 2 DNA does not affect expression in Xenopus laevis oocytes.
AB  - The early region 2a (E2a) of adenovirus type 2 (Ad2) DNA codes for a 72,000
      dalton DNA-binding protein and is expressed in the Ad2-transformed hamster cell
      line HE1 but not in cell lines HE2 and HE3 (H. Esche, J. Virol. 41:1076-1082,
      1982; K. Johansson et al., J. Virol. 27:628-639, 1978). An inverse correlation
      between DNA methylation at the 5'-CCGG-3' sites of the E2a region and of gene
      expression in these cell lines has been observed (L. Vardimon et al., Nucleic
      Acids Res. 8:2461-2473, 1980). When the cloned E2a region of Ad2 DNA is
      methylated in vitro at the 5'-CCGG-3' sites, the gene is not transcribed after
      being injected into the nuclei of Xenopus laevis oocytes, whereas unmethylated
      DNA is expressed (L. Vardimon et al., Eur. J. Cell Biol. 25:13-15, 1981; L.
      Vardimon et al., Proc. Natl. Acad. Sci. U.S.A. 79:1073-1077, 1982). These data
      demonstrate that DNA methylation is directly involved in the shut-off of
      transcription. In the present communication we investigated in detail the control
      region of the gene for the DNA-binding protein in Ad2-transformed cell lines and
      showed that the first late control region (map coordinate 72 on the viral DNA) of
      the E2a region is present in its entirety in cell lines HE1, HE2, and HE3. The
      HaeIII sites (5'-GGCC-3') in the E2a region in all three cell lines were not
      methylated. When the DNA methyltransferase BsuRI was used, all 5'-GGCC-3' sites
      in the cloned E2a region of Ad2 DNA were methylated in vitro. It was shown that
      methylation of these sites did not inhibit the expression of this viral gene in
      X. laevis oocytes. Thus, for methylation to affect gene expression in the E2a
      region it has to occur at specific sites (e.g., 5'-CCGG-3') which may be
      different for other genes.

PMID- 14582199
TI  - Kinetics of accumulation and processing of simian virus 40 RNA in Xenopus laevis
      oocytes injected with simian virus 40 DNA.
AB  - We examined the kinetics of accumulation and processing of simian virus 40 (SV40)
      RNA in stage 6 oocytes of Xenopus laevis microinjected intranuclearly with SV40
      DNA. The rates of synthesis and degradation, cellular distribution, size, and
      sequence specificity of radiolabeled SV40-specific and endogenous oocyte RNA were
      determined. The kinetics of accumulation of SV40 RNA were biphasic, with greater
      than 90% of the viral RNA turning over in the nucleus with a half-life of 20 to
      40 min. Although most of the primary transcription products were multigenomic in
      length, some stable polyadenylated SV40-specific RNA similar in size and sequence
      to late 19S mRNA accumulated in the cytoplasm with time. Differences in strand
      preference, efficiencies of transcription termination and polyadenylation, and
      the splice sites used in the synthesis and processing of SV40 RNA in Xenopus
      oocytes and monkey cells were noted. However, these differences were
      quantitative, rather than qualitative, in nature. Consequently, they are probably
      due to regulatory rather than mechanistic differences between the two cell types.
      We therefore conclude that Xenopus oocytes may be a useful system for studying
      both mechanistic and cell type-specific regulatory aspects of mRNA biogenesis
      from cloned DNAs. However, since only a small percentage of the initially
      synthesized RNA ends up in stable mRNA, it will be important to determine whether
      mutants of cloned DNAs that produce abnormal amounts of stable mRNAs are altered
      in promotion and initiation of RNA synthesis, transcription termination, RNA
      processing, or the stability of the resultant mRNAs.

PMID- 14582200
TI  - Template structural requirements for transcription in vivo by RNA polymerase II.
AB  - Purified simian virus 40 (SV40) DNA is reconstituted into chromatin and
      transcribed by endogenous RNA polymerase II when microinjected into nuclei of
      Xenopus laevis oocytes. We have correlated the kinetics of chromatin
      reconstitution with that of accumulation of virus-specific RNA in this system. A
      delay of approximately 3 h was found in the appearance of appreciable numbers of
      both fully supercoiled molecules and transcriptionally active templates. SV40
      mini-chromosomes, isolated from virus-infected monkey cells with 0.2 M NaCl, also
      exhibited this lag in onset of transcriptional activity when microinjected into
      oocytes. These findings indicate that neither purified SV40 DNA nor SV40 DNA
      containing a full complement of nucleosomes can function as a template for
      transcription in vivo before association with appropriate cellular nonhistone
      chromosomal factors has taken place. In addition, the gradual degradation of
      linear SV40 DNA in oocytes was not sufficient to account for the fact that it was
      much less transcriptionally active than circular SV40 DNA. Taken together, these
      results indicate that the conformational state of the DNA can affect its ability
      to function as a template for transcription in vivo by RNA polymerase II. In
      contrast, transcription by RNA polymerase III of purified, circularized cloned
      DNAs encoding genes for 5S rRNA was detectable long before the injected DNAs had
      time to reconstitute into chromatin. Therefore, the template structural
      requirements for transcription in vivo by RNA polymerases II and III are
      different.

PMID- 14582201
TI  - Linear DNA does not form chromatin containing regularly spaced nucleosomes.
AB  - The topological state of DNA may play a role in regulating chromatin structure
      and gene expression in eucaryotes. To test this hypothesis, the arrangements of
      nucleosomes on circular and unit-length linear simian virus 40 (SV40) DNAs
      incubated in nuclei of Xenopus oocytes were determined by (i) analyzing changes
      in the electrophoretic properties of the DNAs and (ii) examining the patterns of
      DNA fragments resulting from digestions with micrococcal nuclease. Whereas
      circular DNA became associated with nucleosomes that were arranged along the DNA
      at regular intervals of approximately 195 base pairs, linear DNA failed to
      reconstitute into chromatin containing regularly spaced nucleosomes. DNA that
      failed to form proper chromatin was gradually degraded, indicating that histone
      proteins in proper association with DNA may be the cellular component that
      normally protects chromosomal DNA from endonucleolytic attack. When either
      circular or linear DNA was incubated in an in vitro transcription system made
      from a whole-cell extract of HeLa cells, most of the molecules did not associate
      with histone proteins to form regularly spaced nucleosomes. Furthermore,
      linearization of mRNA-encoding DNAs, including SV40, reduces their
      transcriptional activity in Xenopus oocytes to a level comparable to that
      obtained with the in vitro transcription system employed here. Therefore, proper
      association of DNA with appropriate cellular chromosomal factors may be a
      prerequisite for proper transcription by RNA polymerase II.

PMID- 14582203
TI  - Expression of bacterial beta-galactosidase in animal cells.
AB  - A recombinant plasmid containing the gene for bacterial beta-galactosidase,
      situated close to the simian virus 40 early promoter, has been constructed.
      Transfection of CHO, L, and COS-1 cells with this plasmid led to the expression
      and appearance of the enzyme. Using this system, we have developed a series of
      promoter cloning vehicles capable of accepting promoter signals for animal genes.

PMID- 14582202
TI  - Isolation of a Chinese hamster cell mutant with low intracellular
      phosphoribosylpyrophosphate concentration.
AB  - A tritium-adenine suicide procedure was used to select for mutants with reduced
      uptake of adenine from a population of Chinese hamster V79 cells mutagenized with
      ethyl methane sulfonate. In one of the mutant lines isolated, designated KC62,
      the uptake of adenine, hypoxanthine, and guanine was reduced by approximately
      70%. The specific activities, Km values, and Vmax values of adenine
      phosphoribosyltransferase and of hypoxanthine phosphoribosyltransferase were the
      same in extracts from KC62 and from the parental cell line. Metabolic fate
      studies of incorporated [3H]adenine and 3[H]hypoxanthine revealed a metabolic
      block at the level of phosphoribosylation. Determination of
      phosphoribosylpyrophosphate pool size showed that the mutant contained only 25%
      of the phosphoribosylpyrophosphate found in the parent. Its reduced availability
      in KC62 appears to result in a decreased ability to salvage adenine,
      hypoxanthine, and guaninine via phosphoribosylation. Phosphoribosylpyrophosphate
      synthetase from KC62 was shown to have an increased sensitivity to inhibition by
      a variety of nucleotides.

PMID- 14582204
TI  - Capped mRNAs with reduced secondary structure can function in extracts from
      poliovirus-infected cells.
AB  - Extracts from poliovirus-infected HeLa cells were used to study ribosome binding
      of native and denatured reovirus mRNAs and translation of capped mRNAs with
      different degrees of secondary structure. Here, we demonstrate that ribosomes in
      extracts from poliovirus-infected cells could form initiation complexes with
      denatured reovirus mRNA, in contrast to their inability to bind native reovirus
      mRNA. Furthermore, the capped alfalfa mosaic virus 4 RNA, which is most probably
      devoid of stable secondary structure at its 5' end, could be translated at much
      higher efficiency than could other capped mRNAs in extracts from poliovirus
      infected cells.

PMID- 14582205
TI  - Localization of cap-binding protein in subcellular fractions of HeLa cells.
AB  - The 26,000-M(r) cap-binding protein was analyzed by a cross-linking assay in cell
      fractions from uninfected and poliovirus-infected HeLa cells. Cap-binding protein
      was found in the postribosomal supernatant (S-200) and in the ribosomal salt
      wash. The cap-binding protein in the S-200 had a sedimentation coefficient of 5
      to 7S and lacked the ability to restore translation in extracts of poliovirus
      infected cells.

PMID- 14582207
TI  - Perspectives. Bioterror fears, medical-data deluge drive e-records push.

PMID- 14582206
TI  - Inhibition of host protein synthesis and degradation of cellular mRNAs during
      infection by influenza and herpes simplex virus.
AB  - Cloned DNA copies of two cellular genes were used to monitor, by blot
      hybridization, the stability of particular cell mRNAs after infection by
      influenza virus and herpesvirus. The results indicated that the inhibition of
      host cell protein synthesis that accompanied infection by each virus could be
      explained by a reduction in the amounts of cellular mRNAs in the cytoplasm, and
      they suggested that this decrease was due to virus-mediated mRNA degradation.

PMID- 14582208
TI  - Looking beyond the 2001 Census.
AB  - This article outlines the Office for National Statistics' strategic review
      process for the best way of meeting users' future requirements for information
      that has traditionally been collected by taking a census. It reports on a
      possible design for such a census in 2011 but also considers alternative
      approaches to collecting comparable information. The work described in this
      article is being undertaken within ONS and relates essentially to research on the
      census in England and Wales only. The General Register Office for Scotland and
      the Northern Ireland Statistics and Research Agency are, however, carrying out
      similar reviews.

PMID- 14582209
TI  - Key issues in the quality assurance of the One Number Census.
AB  - As part of the 2001 Census, the One Number Census project estimated and adjusted
      the Census database for underenumeration. As a result of the highly innovative
      One Number Census and the Quality Assurance process it encompassed, it was also
      ensured that robust results could be obtained for each local authority area. This
      article examines some of the issues and analyses that were undertaken as part of
      that assessment of the 2001 Census population counts for England and Wales. The
      article firstly highlights the key issues surrounding the implementation of the
      2001 Census fieldwork. The article then explores the 2001 Census results through
      a series of demographic analyses to illustrate the sorts of issues investigated
      during the One Number Census Quality Assurance process itself. These analyses
      look at the patterns contained within the results, and comparisons with key
      alternative sources of population counts. Overall, these in-depth analyses and
      investigations provide further credence to the plausibility of the One Number
      Census results.

PMID- 14582210
TI  - Implications of 2001 Census for local authority district mid-year population
      estimates.
AB  - ONS published mid-2001 population estimates for England and Wales based on the
      2001 Census in October 2002. Mid-2001 estimates were also produced, but not
      published, rolled forward from the 1991 Census. By considering the differences
      between these two estimates, ONS is able to assess how accurate estimates of
      population change have been between mid-1991 and mid-2001. Results of this
      comparison at national and regional levels have already been published on the
      National Statistics website. This article concentrates on the differences at
      local authority district level. Analyses of these differences within the article
      are in three parts-basic descriptive statistics, comparison of the local
      authority districts as a proportion of their national totals, and more complex
      multiple regression analysis. The implications of these results are then assessed
      and recommendations put forward to help improve the mid-year estimates in the
      following decade. Improvements will also come through other studies such as the
      National Statistics Quality Review on international migration.

PMID- 14582211
TI  - A demographic statistics service for the 21st century.
AB  - This article provides a summary of a review of the uses made of population and
      household statistics across government in England and Wales, setting out the
      policy and statistical impacts of demographic change. It looks at the broad span
      of government uses of population and household statistics--and what these uses
      imply for the qualities inherent in these statistics. The article considers
      alternative population definitions and refers to several ongoing projects that
      are aiming to enhance demographic statistics in England and Wales. Following an
      analysis of the key issues relating to the implementation of an improved
      statistical service, a series of action points for ONS emerging from the review
      is set out.

PMID- 14582212
TI  - Improving collections in the ED.

PMID- 14582213
TI  - Billing and coding update.

PMID- 14582214
TI  - Feeling comfortable with not knowing.

PMID- 14582215
TI  - Implications of lack of concordance among oncologists for evidence-based medicine
      derived clinical guidelines.

PMID- 14582216
TI  - Novel approaches in the treatment of multiple myeloma.
AB  - Despite all the new advances, treatment of multiple myeloma remains very
      challenging. Table 6 summarizes the outcomes of some of the commonly used
      treatments from different clinical trails. Treatment with conventional
      chemotherapy alone resulted in median survival from 18 to 30 months. Aggressive
      treatments like VBMCP (vincristine, bleomycin, melphalan, cyclophosphamide,
      predisone) although resulting in higher response rates, resulted in higher
      treatment-related mortality and did not have any effect on median and 5 year
      survival. High dose chemotherapy with stem cell support increased the median
      survival to around 60 months and resulted in durable complete responses in a
      significant number of the patients. Some of the newer and promising treatments
      for multiple myeloma are summarized in Table 7.

PMID- 14582217
TI  - New therapeutic approaches to non-Hodgkin's lymphomas.

PMID- 14582218
TI  - The chronic leukemias: current and novel therapeutic approaches.
AB  - Recent developments with targeted therapies have expanded the therapeutic
      armamentarium (Table 1) for patients with both CLL and CML. Significant advances
      in allogeneic and autologous donor transplantation have increased the patient
      eligibility pool and reduced the toxicities while improving upon long term
      survival results.

PMID- 14582219
TI  - The latest treatment advances for acute myelogenous leukemia.
AB  - The research into pathogenesis and mechanisms behind AML is advancing rapidly,
      but in general, translation into global application for the majority of patients
      is wanting. As more becomes known about the cytogenetic and molecular
      characteristics of leukemia cells and the pathways of leukemogenesis are further
      elucidated, it is hoped that future therapies will be directed more specifically
      toward the least toxic method to eradicate clonal malignant cells. HLA
      haploidentical and alloBMT using KIR mismatch may dramatically improve survival
      for many more patients.

PMID- 14582220
TI  - Future prospects for patient care utilizing autologous lymphoid and hematopoietic
      stem cells.

PMID- 14582221
TI  - The relationship between depression and cancer survival.

PMID- 14582222
TI  - Persistent candidemia in a leukemic after allogeneic transplantation.

PMID- 14582223
TI  - Neoadjuvant therapy with high dose chemotherapy via isolated pelvic intra
      abdominal perfusion with bone marrow stem cell support for advanced endometrial
      cancer.

PMID- 14582224
TI  - New monoclonal antibodies for hematologic malignancies (and breast cancer).

PMID- 14582225
TI  - Violent deaths in Rhode Island, 1999-2002.

PMID- 14582226
TI  - [Genetic control of development of the Malpighian vessels in Drosophila
      melanogaster].
AB  - Malpighian tubules of insects are a functional analog of mammalian kidneys and
      serve as a classical model for studying the structure and functions of transport
      epithelium. The review contains the data on structural organization, functioning,
      and formation of the Malpighian tubules during embryogenesis in Drosophila
      melanogaster. Various systems of genes are described that control the program of
      development of the renal (Malpighian) tubules in D. melanogaster. A special
      attention is paid to the ways of signal transduction and factors involved in cell
      differentiation, proliferation, and morphological transformation during
      development of the Malpighian tubules. Evolutionarily conservative genetic
      systems are considered that are involved in the control of development of both
      the renal epithelium of Drosophila and mammalian kidneys. A relationship was
      noted between the disturbed balance of genetic material and congenital defects of
      the human excretory system.

PMID- 14582227
TI  - [Molecular mechanisms of thymocyte differentiation].
AB  - A review of the main molecular events occurring during differentiation of T
      lymphocytes in the thymus: T-cell specialization of early intrathymic precursors,
      formation and expression of antigen receptor, formation of antigen recognizing
      cell repertoire, and alpha beta/gamma beta- and CD4/CD8-commitment. The
      mechanisms of glucocorticoid-induced apoptosis of thymocytes and its blockade
      during antigen-dependent activation are considered. A special attention is paid
      to the analysis of intracellular signals underlying the clonal selection of
      thymocytes.

PMID- 14582228
TI  - [Different methods of forming root systems in plants using maize and flax
      seedlings as examples].
AB  - Comparison of the appearance and development of lateral roots in the flax and
      maize seedlings has shown the way of root branching in the flax, as distinct from
      that in most plants. Some primordia in the flax main root did not develop
      immediately into lateral roots, but remained quiescent, which determines
      different reactions of the maize and flax root systems to experimental
      influences. Decapitation of the main root in the maize did not leads to a
      significant increase in the number of lateral roots, while in the flax, their
      number noticeably increased due to the development of previously quiescent
      primordia into lateral roots. The treatment with synthetic auxin did not induce
      the formation of additional primordia and lateral roots in the maize roots. In
      the flax, the number of primordia increased significantly and that of lateral
      roots increased to a somewhat lesser extent. Apparently, the development of a
      primordium into a lateral root proceeds in two stages and they have different
      regulation.

PMID- 14582229
TI  - [Localization of crystallins in Muellerian cells in the grass frog retina].
AB  - Cell localization of 23 kDa- and 35 kDa-crystallins in the retina of adult common
      frogs Rana temporaria L. was studied using indirect immunofluorescence. Intense
      specific fluorescence of both crystallins was observed all over the retina, in
      both periphery and central area. It was localized in elongated radially oriented
      cells, whose bodies were located in the inner nuclear layer. These cells gave
      many fluorescing processes in the same layer and main processes in the outer
      nuclear and ganglion layers, one in each. The processes formed a strong network
      of fibers around the photoreceptor and ganglion cells. Intense fluorescence was
      also observed in the layer of nerve fibers and adjoining inner limiting membrane.
      The distribution and morphology of crystalline-containing cells mostly coincides
      with what is known for the Muller cells of vertebrate eye. The identity of the
      cells we described and Muller cells was also confirmed using the antiserum to
      glial fibrillary acidic protein.

PMID- 14582230
TI  - [Effect of stress on postnatal growth in weight of rat body and adrenal gland].
AB  - Seven-week male Wistar rats weighing 145-155 g were housed 10 (control) or 20
      (crowded) per cage (50 x 35 x 15 cm). Groups of control and crowded animals were
      decapitated within 0.5, 1, 3, 7, 14, 21, 28, 35, 56, 70, and 98 days of
      experiment. The keeping of rats in crowding conditions induced chronic stress,
      which developed, according to phase changes in plasma concentration of
      corticosterone and adrenal content of cholesterol, through the stages alarm,
      resistance, and exhaustion. The postnatal growth of body weight in the stressed
      rats was behind that in the control. Under the crowding conditions, the adrenal
      weight did not undergo significant increase, since the stress-induced hypertrophy
      of the zona fasciculata was compensated by the proportional suppression of the
      postnatal growth of the zona reticularis. After 56 days, the postnatal growth of
      the hypertrophied fascicular zone was delayed in the experimental rats.

PMID- 14582231
TI  - [Change in intensity of respiration in development of some invertebrates].
AB  - We studied the dynamic of respiration intensity during ontogenesis of flat worms
      (Dugesia tigrina), molluscs (Anodonta piscinalis and Viviparus viviparus, and
      insects (Leptinotarsa decemlineata). In planarians that reproduce vegetatively,
      the intensity of respiration increases just after fission and decreases at the
      subsequent phases of growth. In A. piscinalis, this index of metabolism increases
      during embryonic and early larval development and decreases at the later
      developmental stages. In V. viviparus, which develops in the female genital
      tract, the intensity of respiration remains unchanged during embryogenesis and
      decreases during late embryogenesis and subsequent phases of growth. In L.
      decemlineata, the intensity of respiration increases during embryonic and early
      larval development and then decreases to undergo cyclic changes times to molts.
      This index markedly decreases in the pupae, increases in the beginning of
      imaginal period, and then again decreases.

PMID- 14582232
TI  - [Cytogerontology at the beginning of the third millenium: from "correlative" to
      "gist" models].
AB  - For the most part, research in the area of cytogerontology, i.e., investigation
      of the mechanisms of aging in the experiments on cultured cells, is carried out
      using the "Hayflick's model". More than forty years have passed since the
      appearance of that model, and during this period of time, very much data were
      obtained on its basis. These data contributed significantly to our knowledge of
      the behavior of both animal and human cultured cells. Specifically, we already
      know of the mechanisms underlying the aging in vitro. On the other hand, in my
      opinion, little has changed in our knowledge of the aging of the whole organism.
      In all likelihood, this can be explained by that the Hayflick's model is, like
      many others used in the experimental gerontology, correlative, i.e. based on a
      number of detected correlations. In the case of Hayflick's model, these are
      correlations between the mitotic potential of cells (cell population doubling
      potential) and some "gerontological" parameters and indices: species life-span,
      donor age, evidence of progeroid syndromes, etc., as well as various changes of
      normal (diploid) cells during long-term cultivation and during aging of the
      organism. It is, however, well known that very frequently a good correlation has
      nothing to do with the essence (gist) of the phenomenon. For example, we do know
      that the amount of gray hair correlates quite well with the age of an individual
      but is in no way related to the mechanisms of his/her aging and probability of
      death. In this case, the absence of cause-effect relationships is evident, which
      are, at the same time, indispensable for the development of gist models. These
      models, as distinct from the correlative ones, are based on a certain concept of
      aging. In the case of Hayflick's model, such a concept is absent: we cannot
      explain, using the "Hayflick's limit", why our organism ages. This conclusion was
      convincingly confirmed by the discovery of telomere mechanism which determines
      the aging of cells in vitro. That discovery initiated the appearance of theories
      attempting to explain the process of aging in vivo also on its basis. However, it
      has become clear that the mechanisms of aging of the entire organism, located,
      apparently, in its postmitotic cells, such as neurons or cardiomyocytes, cannot
      be explained in the framework of this approach. Hence, we believe that it is
      essential to develop "gist" models of aging using cultured cells. The mechanisms
      of cell aging in such models should be similar to the mechanisms of cell aging in
      the entire organism. Our "stationary phase aging" model could be one of such
      models, which is based on the assumption of the leading role of cell
      proliferation restriction in the processes of aging. We assume that the
      accumulation of "senile" damage is caused by the restriction of cell
      proliferation either due to the formation of differentiated cell populations
      during development (in vivo) or to the existence of saturation density phenomenon
      (in vitro). Cell proliferation changes themselves do not induce aging, they only
      lead to the accumulation of macromolecular defects, which, in turn, lead to the
      deterioration of tissues, organs, and, eventually, of the entire organism,
      increasing the probability of its death. Within the framework of our model, we
      define cell aging as the accumulation in a cell population of various types of
      damage identical to the damage arising in senescing multicellular organism. And,
      finally, it is essential to determine how the cell is dying and what the death of
      the cell is. These definitions will help to draw real parallels between the
      "genuine" aging of cells (i.e., increasing probability of their death with "age")
      and the aging of multicellular organisms.

PMID- 14582234
TI  - Lettura magistrale. Perspectives of occupational health in the changing world of
      work (with special reference to control of occupational and work-related
      morbidity).

PMID- 14582233
TI  - [Appearance of dendritic cells in the basal layer of the corneal epithelium
      during metamorphosis of the grass frog Rana temporaria L].
AB  - A population of dendritic cells was found at the light optic level in the basal
      layer of the corneal epithelium in Rana temporaria L. The cells had wide short
      processes which penetrated between neighboring epithelial cells. The bases lied
      on the basal membrane while the bodies are slightly elongated perpendicularly to
      the epithelium surface. The appearance of dendritic cells coincided in time with
      the beginning of metamorphosis of the tadpoles and their number increased by the
      end of metamorphosis. The dendritic cells we described were similar in their
      morphology to the Langerhans cells.

PMID- 14582235
TI  - [Occupational epidemiology in Italy].
AB  - The development of Occupational Epidemiology in Italy is closely correlated with
      the political and social awareness of the needs of preventive strategies in the
      workplace. In the late '60s the Trade Unions supported a model of intervention
      based on the involvement of the so-called "Homogeneous group of workers" in the
      validation of the preventive measures taken on the workplace. In spite of the
      shortcomings of the model, it was extremely effective resulting in enhanced
      perception of the priority of preventive strategies and in the formation within
      the National Health Service of the Occupational Health Services. In Italy over
      the period 1973-2002 there has been an impressive trend of research in field of
      occupational epidemiology (a search on Medline shows an increasing trend over the
      years and, in terms of international comparison, higher figures than in Germany,
      France and Spain). Occupational Epidemiology is now present in the activities of
      the local Occupational Health Services and in the teaching activities of the
      Medical Schools throughout the country.

PMID- 14582236
TI  - [Occupational epidemiology: contributions and prospects].
AB  - Occupational epidemiology (OE) played a major role in the development of modern
      occupational medicine from a practice concerned with individual disease cases to
      a practice concerned with populations and their working environment. One of the
      greatest contribution was the identification of occupational carcinogenic agents.
      OE also represented the foundation for the development of environmental
      epidemiology which represents today a major research and public health activity.
      OE has, in perspective, still several contributions to provide to the development
      of occupational health, including the systematic description of the present
      burden of work-related disease on our society; the investigation of the
      mechanistic steps linking exposure to disease onset, in order to identify, in
      parallel, more adequate and effective prevention measures; the validation of
      health surveillance and screening programs at work; the study of the "causative"
      link between exposures and effects; and the risk assessment for an evidence based
      management of the health risks at work.

PMID- 14582237
TI  - [Epidemiologic surveillance in occupational carcinogenesis].
AB  - Research on occupational cancer epidemiology has been an important area of
      occupational health in Italy. While according to epidemiological estimates the
      proportion of all cancers attributable to occupational factor is about 4%, the
      number of compensated occupational cancers in Italy is remarkably lower.
      Re.Na.M., OCCAM and ISOD projects are example of epidemiological surveillance and
      can serve as basis for ad hoc studies.

PMID- 14582238
TI  - [Molecular epidemiology in occupational medicine: methodological features and
      impact of individual genetic susceptibility].
AB  - A review of main methodological questions regarding biomarkers is reported
      focusing on validation, laboratory variability, study design and statistical
      analysis. The indicated perspective is the setup of protocols finalized at the
      study of multiple panels of genotoxicity biomarkers taking into account the
      influence of gene-environment interaction at low doses, of the modulation of the
      biomarkers associated to the genetic polymorphism. An overview on the influence
      of metabolic and DNA repair polymorphisms on biological indicators of genotoxic
      risk in occupational, environmental or life-style exposure is also presented.
      Genetic polymorphisms that influence human genotoxic risk are those of
      glutathione s-transferase and cytochrome P450 in exposure to polycyclic aromatic
      hydrocarbons (PAHs), those of N-acetyltransferase in both occupational and
      environmental exposures to aromatic amines (AAs) and similar compounds. Lastly
      recent and important studies, on the effect of the newly discovered polymorphisms
      affecting DNA repair enzymes on the modulation of genotoxic risk linked to life
      style (i.e., aflatoxin and PAHs from diet) and smoking behaviour and to
      environmental genotoxic exposure, are reported. To date biomarkers represent a
      new tool for epidemiological research in occupational medicine and they could
      represent a valid instrument for group evaluation but they are not useful for the
      risk assessment on individual basis. To achieve this objective it is necessary to
      demonstrate a stronger association with the endpoint that perhaps the future
      development of genetic and molecular epidemiology will make possible.

PMID- 14582239
TI  - [Assessment of appropriateness and verification of interventions in the
      professional practice of the occupational physician].
AB  - Evaluation of Occupational Health Practice is both an intriguing research field
      and an essential tool to assure the quality of intervention. The objectives of
      this paper are: (i) to define the principles of evaluation and the role of
      quality assurance of intervention, (ii) to define the principles of audit of
      professional practice, (iii) to outline the role of research in evaluating and
      improving intervention and other practice.

PMID- 14582240
TI  - [Methodology in occupational and environmental epidemiology].
AB  - The close links between environment and health have long been known. The
      methodological bases for this study were especially developed in the occupational
      settings, and notably so in the study of occupational carcinogens. Many
      pollutants recently spread from the confined work places to the general
      environment (e.g., lead, benzene, PAHs, asbestos, noise) either as effluents of
      industrial sites or as exhausts of diverse environmental combustion sources
      (e.g., traffic, heating). The methodologies developed in the occupational
      settings proved extremely useful in addressing these new environmental problems.
      Main experiences in Italy include the study of a large residential population
      exposed to dioxin; the study of benzene and PHA's exposure in the city
      environment; the effect of point industrial pollution sources on the surrounding
      territory; the short and long term effect on respiratory and cardiovascular
      health outcomes and functions after exposure to PM10 and 2.5 in large cities.

PMID- 14582241
TI  - [Causality link in criminal law: role of epidemiology].
AB  - This paper focusses on the role of epidemiology in demonstrating causality in
      criminal trials of toxic tort litigation. First of all, consideration is given of
      the specificity of the criminal trial and of the role of the epidemiologist as
      expert witness. As a second step the concept of causality is examined separating
      general from specific (individual level) causality. As regards general causality,
      strategies based on some criteria (example: Bradford-Hill criteria) are
      contrasted with approaches that do not consider causality a matter of science but
      one of health policy; and specific methods frequently used (meta-analysis, risk
      assessment, International Boards evaluation,....) are discussed, with special
      reference to the adoption of high-level standards and to the context of cross
      examination. As regards individual level causality the difficulties of the
      epidemiologic approach to such evaluation are stressed, with special reference to
      topics like expected value, attributable risk, and probability of causation. All
      examples are taken from Italian court trials. A general comment on the
      difficulties of using the criminal trial (dominated by the "but for" rule) for
      toxic tort litigation and on the opportunity to switch to trials (civil,
      administrative) with less stringent causal rules ("more probable than not") is
      offered, with a consideration also of what are called "class actions".

PMID- 14582243
TI  - [Bladder cancer and occupational activity].
AB  - Bladder cancer is important in Occupational Medicine and in Occupational
      Epidemiology. Multicentric studies and pooled analysis have contributed in the
      last few years to the identification and characterization of several risk factors
      for bladder cancer, both occupational and non-occupational. Currently, it is a
      research priority the study of genetic susceptibility and its interaction with
      environmental and occupational exposure to the various bladder cancer risk
      factors. Bladder cancer management entails a few aspects that directly involved
      the Occupational Phisycian in different activities such as biological monitoring
      of chemicals, known or suspected bladder carcinogens, health surveillance,
      fitness for work, the return to work of the bladder cancer patients and finally
      epidemiological surveillance and health promotion.

PMID- 14582242
TI  - [European multicenter cross-sectional study on exposure to low doses of benzene].
AB  - A cross-sectional multicenter european study has been carried out to evacuate the
      relations between exposure to low level of benzene and biological markers of
      internal dose (t,t-MA, S-PMA) and early biological effect (DNA-SSB). The research
      has shown significantly increased levels (adjusted for smoking habits) of the
      urinary excretion of t,t-MA, S-PMA and DNA-SSB in petrochemical workers (mean
      benzene level = 5,694 micrograms/m3) but not in filling station attendants,
      traffic police officers, and bus drivers compared to referent workers. Dose
      response relations were detected between benzene air levels, t,t-MA, S-PMA and
      DNA-SSB in petrochemical workers, with significantly increased levels of DNA-SSB
      detected for benzene exposure levels in the range 391-1,800 micrograms/m3 (0.12
      0.58 ppm).

PMID- 14582244
TI  - [Biomechanical overload diseases: epidemiologic data].
AB  - Work-related musculoskeletal disorders are a major problem for industrialised
      societies, particularly in view of the elevated prevalence of low back pain (LBP)
      and carpal tunnel syndrome (CTS) among manual workers. Epidemiological studies
      show that work-related risk factors, such as lifting, twisting, bending, exposure
      to whole body vibration, and prolonged postures are prominent risk factors for
      LBP. For CTS, repetitive movements, hand-arm vibrations and use of forceful hand
      movements appear to be the major work-related risk factors. Psychological and
      psychosocial factors can also affect the onset of both disorders. This review
      provides an overview of the main evidence in the scientific literature on these
      issues.

PMID- 14582245
TI  - [Evaluation of the impact of the environment on health: the studies on the rising
      pollution].

PMID- 14582246
TI  - [Stress, socio-occupational factors and cardiovascular risk: Italian experience].
AB  - A short overview about the main results obtained in some Italian studies on
      stress, occupation and cardiovascular disease is presented. Objective
      occupational discomfort and stress perception are related to biological changes
      in cathecolamine excretion and blood pressure. The latter, in males, is proposed
      as a biological index of stress perception. However it is not clear if these
      changes are a consistent contribution in increasing prevalence of major
      cardiovascular risk factors, coronary disease severity and incidence, although
      case fatality seems undoubtedly associated to low socio-occupational status.
      Consequent directions for future research are proposed.

PMID- 14582247
TI  - [A new model of health surveillance: lessons learned from epidemiology].
AB  - Occupational medicine in the last few years is trying to tune its objectives to
      the changing needs of the working world. The continuous reduction of incidence of
      work related diseases progressively substituted with chronic degenerative ones,
      suggests a different strategy to prevent occupational diseases and to protect
      workers health. Health surveillance should not be limited only to draw up the
      work qualification but should be the starting point to plan intervention useful
      both to workers and to the general population. Corner stone of this endeavour is
      the epidemiological research focused on the improvement of quality of life.

PMID- 14582248
TI  - [Can exposure to low doses have effects?].
AB  - This paper aims to discuss the scientific evidence to answer the question in the
      title. After a brief mention of the fundamental toxicological principles of risk
      assessment (hazard, exposure, susceptibility, risk), the concepts of dose
      response, dose-effect and threshold-dose are presented. The difference between
      adverse effects with and those without a threshold is highlighted, together with
      the corresponding methodologies used in risk assessment for the definition of the
      limit values, i.e. the No Observed Adverse Effect Level (NOAEL) and Safety Factor
      (SF) method and the Virtually Safe Dose (VSD) method. The two methods correspond
      to two different types of effect, i.e. deterministic and stochastic, and to two
      different shapes of the dose-response curve at low doses. The various possible
      meanings (semantic, toxicological and practical) of the terms "low doses" are
      discussed: a dose (or concentration) may be low because it does not cause
      measurable adverse effects (as from Paracelsus' aphorism) or because it is too
      low to be (analytically) measurable or because it is close to or within the
      "normal" values of a reference population or because it is well below the
      exposure limit(s). These various concepts are presented also in relation with the
      controversial concept of "moderate risk" introduced by a recent Italian
      legislation (D. Lgs 25/02) on the protection of the workers against chemical
      risk. It would not be appropriate to set a level of risk simply based on the dose
      (or the level of exposure) without considering the two other components of risk,
      i.e. hazard and susceptibility, whose estimation also needs a careful and
      competent evaluation by the occupational physician. For a thorough discussion of
      the "moderate risk" concept see a specific paper in these Proceedings. So,
      clinical, epidemiological and toxicological evidence indicates that in some
      individuals, groups of the population or circumstances, adverse effects can be
      observed or expected even at low doses, at which the large majority of the
      population shows no effect. This is due to a number of factors including
      toxicological interactions, immunoallergic mechanisms, metabolic
      hypersusceptibility, both genetic (polymorphism) and acquired (phenotype),
      preexisting traits or diseases, living habits, diet and others. The Authors
      conclude therefore that to ensure the protection of all the workers' health and
      safety, the clinical, toxicological and epidemiological expertise of the
      occupational physician appears to be fundamental and unreplacable.

PMID- 14582249
TI  - [Role of genetic polymorphism in risk assessment].
AB  - Genetic polymorphism is an important factor of individual susceptibility to drugs
      or to toxic substances in environmental and occupational exposure. Although
      polymorphism is never the only responsible of a disease, it can modify both the
      level of risk for adverse effects and the levels of biomarkers after exposure to
      some toxic agents. In this paper two important groups of polymorphic enzymes,
      responsible of the detoxification of exogenous substances, were examined:
      paraoxonase-1, involved in the metabolism of some organophosphorus insecticides,
      and glutathione S-transferases, involved in the detoxification of numerous
      epoxide metabolites. Particularly the role of GSTT1 and GSTM1 polymorphism on the
      biological indicators of 1,3-butadiene has been evaluated. Moreover, the
      influence of delta-aminolevulinic acid dehydratase, enzyme involved in the
      sinthesys of the eme, on the biological indicators of exposure and effect to lead
      has been also examined.

PMID- 14582250
TI  - [Assessment of cumulative risk of mixtures with multiple target organs].
AB  - Humans are exposed to very complex environmental mixtures. In contrast to this
      reality, most laboratory investigations of mixtures, with exception of
      mutagenicity assays, have focused on mixtures comprised of a few chemicals.
      Component-based approaches that use information on the individual chemical
      contained in the mixture are not by themselves sufficient for complex,
      environmental mixtures because significant portions of the mixtures mass are
      unidentified. Assessment of the cumulative risk posed by exposure to multiple
      chemicals is a problem the USEPA's and FDA's program discuss regularly. In USA
      the Food Quality Protection Act of 1996 directs the Office of Pesticide Programs
      to include in its assessments the risk associated with the cumulative effects of
      pesticides that have a common mode of action. organophosphorus pesticides (OPs)
      have been the first class addressed, based on the common mechanism of
      acetylcholinesterase inhibition. Interestingly toxicity studies focussing on
      component-based analysis of mixtures indicated that for chemicals not sharing the
      same target and mechanism, the type of combined action or interaction found when
      each chemical in the mixture was present at clearly toxic effect levels did not
      predict the response observed when each chemical was present at or below the
      lowest observed adverse effect level (LOAEL). Moreover, mixtures of chemicals
      produced toxicity only for those chemicals that showed the same toxic effect on
      the same target organ when given singly at dose above the LOAEL values. However,
      end-points chosen in routine toxicity studies do not offer a wide dynamic range
      of testable, significant responses around and above the NOAEL. So far sensitive
      methods that detect low level changes have not yet been employed in mixtures
      testing protocol. Toxicogenomics integrated functional genomics with classical
      toxicology and we believe that it has great potential to revolutionize mixtures
      research.

PMID- 14582251
TI  - [The precautionary principle: is it applicable to occupational medicine?].
AB  - Precautionary Principle (PP) and its application to environmental and health
      policy appear in the 70's and from that time is introduced more and more
      frequently in different international treaties and conferences on environment and
      health. PP is a risk management policy applied to scientifically uncertain
      circumstances where it is necessary to act against a potentially harmful risk
      factor without waiting for more accurate information. When this situation takes
      place at the workplace, the risk management is an Employer's task. The employer
      can use different instruments, including the occupational physician's advise, to
      reach their target. After identification of possible health and safety risk
      factors and after characterisation of a non-admissible risk for worker's health,
      the Employer must chose which precautionary actions to take, also in function of
      economic, technical and judicial needs and restrictions. This action can be the
      application of measures of "prudent avoidance" through steps such as health
      surveillance, until more radical measures are taken by using P.P. The
      Occupational health specialist that is already operating of the work place with
      characterised and well known risk factors should introduce the instruments, in
      the health surveillance activities, that may detect possibly adverse effects
      related to risk factors characterised by scientific uncertainty. This is very
      important whenever the employers don't have the possibilities or are not
      sensitive enough to take other kinds of precautionary measures. Moreover, the
      occupational physician should play an active role also in the risk assessment
      phase by defining those chemicals or physical agents still characterized by
      scientific uncertainty.

PMID- 14582252
TI  - [Implementation of parliamentary act D. Lgs 25/02 and definition of "moderate
      risk"].
AB  - This paper describes the position of the Joint Working Group of the Italian
      Association of Industrial Hygienists (AIDII), the Italian Society of Occupational
      Health and Industrial Hygiene (SIMLII) and the Italian Society of Toxicology
      (SITOX) on "Analysis of Parliamentary Act D.Lgs 25/02 and role of the Scientific
      Societies in the definition of Limit Values". The positive aspects of the new law
      which implements the European Directive 98/24 are discussed, including the
      abolition of the rigid periodicity of medical examinations as stated by the old
      rule D.P.R. 303/56. The Authors also address various parts of the law which
      appear to be unclear and controversial and highlight the expected difficulties
      arising for the employers and the safety and health professionals during the
      application of this new piece of legislation. Moreover, a number of discrepancies
      are noted between the new Italian law and the original Directive or other current
      Italian rules such as i. the translation of the term "slight risk", as from the
      original Directive, into "moderate risk", and the resulting non compulsoriness of
      health surveillance and biological monitoring of the workers in presence of a
      "moderate risk", ii. the concurrent exclusion, under the same circumstances, of
      the occupational physician from risk assessment procedures and iii. the upward
      modification of the previously established (D.Lgs 277/91) occupational exposure
      limits for lead. Moreover, the Authors examine and criticize--both in semantic
      and in toxicological terms--a recent proposal for the definition of "moderate
      risk" made by an ad hoc Consulting Committee of the Labour Ministry, in which the
      term "moderate" has been interpreted either as "low" or as "irrelevant for health
      effects", clearly two very different meanings. Besides, it would be inappropriate
      to define the conditions of a moderate risk based only on the level of exposure
      to the chemical (expressed as a fraction of the corresponding limit value),
      without considering the two other components of risk assessment for that chemical
      (hazard and susceptibility). Even worse would be the use of simplified models
      based on "algorithms", which might be useful in a preliminary phase of risk
      assessment, but easily could lead to an under- or over-estimation of risk,
      particularly when used by non professionals. In conclusion, the Working Group
      recommend that the new law be amended in order to clarify its most controversial
      aspects, whose misinterpretation could severely jeopardize the protection of the
      workers' safety and health at work.

PMID- 14582253
TI  - [Biomarkers of effects and susceptibility for risk assessment].
AB  - The ambient air of urban centres is polluted with potentially toxic chemicals
      mostly arising from the combustion or fuels used for transport, heating and
      industrial activities. Alongside the risk to the general public, atmospheric
      pollution could be considered an occupational health hazard to professional
      groups, such us traffic police or professional drivers working in urban areas.
      Molecular epidemiology can facilitate health risk assessment by investigating the
      relationship between exposure to environmental pollutants and quantification of
      biomarkers that lie on the pathway of carcinogenesis upstream of clinical
      disease. In particularly, biomarkers of early effects and susceptibility are
      playing an increase role in the investigation of the impact of air pollution on
      human carcinogenesis.

PMID- 14582254
TI  - [CYP1A2, NAT2, and GSTM1 phenotype/genotype modulate human exposure and various
      environmental mutagens: our experience].
AB  - Since some years in our research group has been studied the influence of
      metabolic genotypes on two biomarkers of genotoxic risk (BPDE-DNA adducts and
      urinary mutagenicity) in humans exposed to polycyclic aromatic hydrocarbons
      (PAHs) and aromatic amines. The aim was to identify possible genetic susceptible
      factors capable of modulating individual response to these carcinogens. Humans
      exposed to PAHs: dermatological patients therapeutically treated with coal tar
      based ointments (CT), coke oven workers and chimney sweeps. People exposed to
      aromatic amines will be volunteers after a meal of pan-fried hamburgers and
      smokers. An overview of the results we found until now will be presented.

PMID- 14582255
TI  - [Fumigation of soil and food: assessment of occupational exposure to methyl
      bromide].
AB  - Innovative procedures were developed for the biological monitoring of workers
      exposed to methyl bromide, through the determination of biomarkers of exposure,
      such as bromide in serum, and of biomarkers of the biologically effective dose,
      such as haemoglobin adducts. The effectiveness of the developed techniques for
      the biological monitoring was tested through the analysis of blood samples from
      workers employed in soil fumigation.

PMID- 14582256
TI  - [Management of combined exposure to chemical agents: an operative proposal].
AB  - The Decree 25/2002 introduces the duty, in case of activities involving exposure
      to several chemical agents, to evaluate the risk "on the basis of the risk
      presented by all such chemical agents in combination". Yet, in the Decree, no
      principles or formal methods are defined to perform such evaluation. Waiting for
      specific technical instructions, we propose a scheme for the management of the
      "combined risk", inspired to the formal criteria and suggestions of the American
      Agencies ACGIH and OSHA. Advantages and limits of the proposed scheme are
      discussed.

PMID- 14582257
TI  - [Assessment of occupational skin exposure: proposal of a check-list].
AB  - The dermal risk assessment requires simplified methodologies to understand the
      role played by the skin. The conceptual models proposed to this aim are founded
      on theoretical assumptions and experimental data, but their use in occupational
      settings shows many difficulties. For this end we have drawn up a check-list that
      includes six sessions and allows to obtain a preliminary dermal exposure
      evaluation subdivided on hazard bands.

PMID- 14582258
TI  - [Definition of neurotoxic risk based on the benchmark dose in vitro: illustration
      with experimental models based on the use of known neurotoxic substances].
AB  - The BMD approach has been used to compare the cell viability (MTT assay) of
      different rat (C6 and PC12, glial and neuronal, respectively) and human cell
      lines (D384 and SK-N-MC, glial and neuronal, respectively) after 24-h exposure to
      the following neurotoxic substances: Manganese Chloride (MnCl2), Methyl-mercury
      (Me-Hg) and the enantiomers of Styrene Oxide (SO). For all rat and human cell
      lines, the potency of the examined compounds was: MnCl2 < S-SO < R-SO < Me-Hg. A
      preliminary comparison with in vivo toxicity data for these substances gave rise
      to consistent results. Whereas a reasonable agreement between in vitro and in
      vivo data has been found for Mn and styrene oxide, a wide scatter of LOAEL has
      been reported for Me-Hg and these appear to be either much higher or lower than
      the BMD for the MTT assay we observed in vitro.

PMID- 14582259
TI  - [Definition of acceptable operator exposure levels (AOELs) to pesticides].
AB  - A guidance document entitled "Recommended method for the establishment of
      Acceptable Operator Exposure Levels" has been prepared within the EU 5th
      Framework program. The paper describes the main outcomes of the project and the
      issues that apply particularly to agricultural workers and bystanders and the
      difficulties in developing an agreed uniform approach. The scientific basis of
      the process is discussed, to be used by the European Commission and Member States
      when making decision about the inclusion of an active substance in Annex 1 of
      Directive 91/414/EEC.

PMID- 14582260
TI  - [Project of the historical monograph on the "Origins of Occupational Medicine
      Associations in the world"].
AB  - The present contribution regards the project of the historical monograph on the
      Origins of OH associations in 23 countries, and in particular the chapter on the
      Origins of the Italian Society of Occupational Health. The Italian chapter is
      aimed at studying the foundation of the Italian Society of Occupational Health
      (Naples, October 12, 1929, within the 8th National Congress of Occupational
      Health) and the first decades of its activity. On account of the complexity and
      variety of the scientific and social context as well as the particular political
      period considered, the contribution is divided into 4 different parts. The first
      deals with the foundation of the Italian Society of Occupational Health and its
      statutory organization. The second part treats the role and presence of the
      discipline in the university world as well as the relationships with other
      cultural institutions such as academies. The third part concerns the law frame
      (specially as to accidents and work-related diseases) within which the activity
      of the Italian Society of Occupational Health has started and developed. The
      fourth part analyses the fascist corporative system and the role played by the
      trade unions in promoting better life and working conditions, with common issues
      also with the programmes of the Italian Society of Occupational Health. Finally,
      some closing remarks and references are provided.

PMID- 14582261
TI  - [Biological effects of exposure to electromagnetic fields: introduction].
AB  - A widespread agreement on the presence, if any, of an association between non
      deterministic effects and exposure to electromagnetic fields (ELF and RF-MW) has
      not been reached yet. Some critical points of the pooled analyses of data that
      lead to the conclusion of the International Agency for Research on Cancer (IARC)
      are examined. While waiting for more well planned scientific studies, it seems
      important for scientific experts to give the most sober interpretation of current
      data, considering the widespread and growing attention of the general population
      for this subject.

PMID- 14582262
TI  - [Experimental data on extremely low frequency (ELF) electromagnetic fields].
AB  - At the current state of knowledge, the biological effects both in vitro and in
      vivo connected to low frequency electromagnetic fields (ELF) are not univocally
      interpreted. Indeed a lot of literature seems strictly related to the particular
      experimental procedure depending both on the biological target and the exposure
      features under consideration. The best studied biological parameters in vitro are
      kinetics of cell proliferation, change in enzymatic activities, intramembrane
      ionic flux and integrity of chromosome complement. In general, the study on
      genotoxic effects induced by simultaneous exposure to electromagnetic fields and
      known chemical or physical mutagenes is based on the theory that electromagnetic
      fields may interfere with mutagenic substances rather than affect directly
      genetic material. In addition, studies in vivo confirm different results both in
      different animal species and in different (nervous, neuroendocrine, immunitary
      systems). Finally, in order to evaluate the wide research activity on this
      subject, we need to take into account the main standard criteria adopted by the
      world scientific community, such as the peer review process and the confirmation
      of experimental data by means of independent repetitions.

PMID- 14582263
TI  - [Experimental data on radiofrequency].
AB  - Since 1996, there has been a flurry of scientific activity to evaluate the
      possibility that cellular telephone use may cause brain tumors, reflecting the
      rapid increase in the use of these phones throughout the world. Overall, the
      epidemiologic and laboratory studies to date have ruled out with a reasonable
      degree of certainty that cellular telephones cause cancer, at least for durations
      of use up to 5 years. RF signals from cellular telephones are not genotoxic and
      cannot directly damage DNA, and are thus unlikely to be in itiators; hence the
      risk of cancer from a thermal or non-thermal mechanism would be one that, if
      anything, promotes tumor growth. However, there is no convincing evidence from
      animal experiments or epidemiologic research that RF signals can promote tumor
      growth. If RF exposure is assumed to act by promoting the growth of an underlying
      lesion, then the large numbers of recent cellular phone users who have been
      studied are likely to have been sufficient to detect such an effect, but none has
      been found and there is no known biological mechanism that supports a causal
      relation and no evidence of adverse effects in laboratory animals.

PMID- 14582264
TI  - [Effects on function of human lymphocytes exposed to electromagnetic fields with
      a frequency from 1,500 to 2,000 MHz].
AB  - Normal human peripheral blood lymphocytes were irradiated for 10 or 5 min with
      frequencies from 1.5 to 2.0 GHz. The frequency of 1.8 GHz overlaps that of mobile
      phones and leads to a significant reduction of the T-cell mediated antibacterial
      activity.

PMID- 14582265
TI  - [Hypersensitivity syndrome].
AB  - We present a review on the electromagnetic hypersensitivity (EHS), a fenomenon
      where individuals experience adverse health effects while using, or being in the
      vicinity, of electric, magnetic or electromagnetic field sources and devices.
      Apparently, symptoms can be induced by both low and high frequencies, even at low
      level, and can vary substantially among different individuals. Scientific data do
      not support the hypothesis of a causal relationship between fields and EHS, even
      if knowledge is largely incomplete. Further studies in this field are needed.

PMID- 14582266
TI  - [Risk of childhood leukemia and environmental exposure to ELF electromagnetic
      fields].
AB  - We present the results of current epidemiological research on the association
      between ELF magnetic fields and neoplasm. ELF magnetic fields were considered as
      'possibly carcinogenic to humans (Group 2B)' by IARC. The evidence was limited to
      childhood acute leukemia and to chronic leukemia (associated to occupational
      exposure) in adults.

PMID- 14582267
TI  - [National and international standards for limiting exposure to electromagnetic
      fields].
AB  - Over recent years the possibility that adverse effects on health could result
      from exposure to electromagnetic fields has become one of considerable
      scientific, political and economic importance. In response to this, there has
      been intense activity, both at the international and national level, on the
      evaluation of biological effects literature and assessment of health hazards of
      human exposure to non-ionizing electromagnetic radiation. The health authorities
      of an increasing number of countries, including Italy, become involved in the
      development of recommendations, regulations or technical advice to limit the
      exposure of the workers and the general public and they are looking to the
      international organizations, particularly to the International Commission on Non
      Ionizing Radiation Protection (ICNIRP), for some guidance in this respect. In
      this paper an attempt will be made to present a comparative analysis of the
      existing or recently proposed standards.

PMID- 14582268
TI  - [The point of view of the Italian Association of Medical Radioprotection:
      proposal of the Italian C.E.M. Observatory].
AB  - Taking in consideration the suggested guide-lines for the health-surveillance on
      workers exposed to N.I.R. and in particular to ELF and radio-frequency, a work
      group of A.I.R.M. suggests the constitution of an italian network for electro
      magnetic fields. An observatory will be founded to value the professional
      exposures and the undue situations of risk, a parallel one will take the census
      of the workers subdivided into classes for exposure levels, pathologies or
      symptomatologies imputable to electro-magnetic fields. This suggestion is
      addressed to the national environmetal hygienists and occupational physicians
      that are interested.

PMID- 14582269
TI  - [Biological response to diverse polymorphic forms of silica].
AB  - Under two different experimental conditions (cleavage of C5 complement fraction
      and human endothelial cells cultures), crystalline and amorphous silica samples
      were tested. Different biological reactions were achieved.

PMID- 14582270
TI  - [Dose-response curve in the study of the effects of exposure to crystalline
      silica].
AB  - The cumulative exposure to crystalline silica (SiO2) implies a linear relation
      between duration of exposure and SiO2 concentration, not always suitable to
      working situations of the last decades. A more correct definition of dose
      response curve has currently to consider also different characteristics of SiO2,
      specifically: possible short-term increases in environmental SiO2 concentration,
      different mineralogical and surface properties of natural silica polymorphs, age
      of SiO2 particles, presence of contaminants on the surface of silica particles or
      even in the respirable fraction of total dust, respirable dust concentration in
      which SiO2 is diluted and other conditions, also affecting the host, able to slow
      alveolar clearance and lengthen permanence time of particles in the lung. Many
      models of definition of cumulative exposure so conceived have been proposed.
      However, to define the occupational risk threshold to contract silicosis and
      other silica-related diseases a number of models of cumulative exposure, i.e.
      biologically effective dose of SiO2, are likely to be delineated that take into
      account only factors specifically present in different occupational situations.

PMID- 14582271
TI  - [Silica, silicosis, and lung cancer: analysis if the literature and mortality
      studies of minor workers in Sardinia].
AB  - Starting from a short review of the recent epidemiological studies available in
      the international literature concerning the association between silica, silicosis
      and lung cancer, the results of two mortality studies performed in Sardinia are
      reported. The first study concerns a 20-year follow-up of 1741 miners employed in
      1973 in two metalliferous Sardinian mines. In the second study the cause specific
      mortality of 724 patients with silicosis, firstly diagnosed by standard chest x
      ray between 1964 and 1970 in our Institute, has been analysed by a cohort study
      extended to December 31, 1997. The findings indicate that the slight increased
      lung cancer mortality observed in these cohorts, more than to the severity of
      radiological silicosis or to the entity of the cumulative exposure to crystalline
      silica dust in itself, was significantly associated to other risk factors as
      cigarette smoking, airflow obstruction and radon-daughters exposure in
      underground mines.

PMID- 14582272
TI  - [The mesothelioma registry].
AB  - The National Mesothelioma Registry (RENAM) have as mains objectives: estimate of
      the incidence of malignant mesothelioma cases in Italy, collecting information on
      past exposure to asbestos, impact and spread of the disease among population,
      identification of unexpected or unknown sources of contamination and promotion of
      research on asbestos exposure and mesothelioma. Some data of Puglia Regional
      Operating Centre are reported. Use of Renam as epidemiological surveillance
      system is underlined in respect to public health and scientific research.

PMID- 14582273
TI  - [Epidemiologic research on asbestos related disease in ENEL SpA electricity
      production plant maintenance].
AB  - Since many years research programs have been set up to study the relationship
      between asbestos occupational exposure and development of asbestos-related lung
      diseases in electricity production plants workers. In the year 2000 a new study
      of asbestos-related lung abnormalities prevalence in italian geothermal and
      idrothermal power plant maintenance workers was planned. The cohort comprised
      3891 subjects. To meet the criteria, only workers in service for at least six
      months before 1990 and still in service at power plants in May 2000 were included
      in the study; chest X-rays were taken and made anonymous. Independent reading of
      X-rays was made by two groups of specialists, and a third reading of selected
      discordant readings X-rays was made by another group of specialists. A further
      diagnostic protocol (including HRCT) was planned when two out of three readings
      showed the presence of asbestos related lung abnormalities. The analysis was made
      on 3063 subjects (78.7% of the cohort). The number of asbestos-related
      abnormalities in two out of three X-ray readings was 122 (4%). The further
      diagnostic protocol, that included occupational and pathological anamnesis and
      HRCT, confirmed an asbestos-related occupational lung abnormalities in 41 cases
      (1.3% out of 3063 subjects). The prevalence of asbestos-related lung
      abnormalities among 3063 power plant maintenance workers was 1.3%. If all the
      cases of lung abnormalities so far detected (data are still provisional) had
      developed only in the power plant environment, and not in previous working
      activities, the prevalence of lung abnormalities would be extremely low. These
      data support the evidence of limited exposure levels to asbestos in this working
      environment And bears witness to the success of preventive measures to control
      this specific risk.

PMID- 14582274
TI  - [Asbestos risk: past and present exposure].
AB  - Occupational asbestos exposure affected a large number of workers during the last
      century. In particular, during the period following the second world war until
      the end of the eighties heavy exposures occurred in several industrial divisions.
      An approximate data can be represented by the number of requests for compensation
      according to the n. 257/1992 ban asbestos law. The National and Regional
      Mesothelioma Registries collect all the cases of this asbestos related disease.
      Analysing these data, the industrial divisions at risk, considering both
      intensity and quality of exposure, emerge with increasing accuracy. The use of
      asbestos in new products has been banned in Italy since 1992. The legislation
      issued during the nineties includes technical guidelines for exposure risk
      control during operations on asbestos containing products, mainly consisting in
      maintenance or asbestos removal. Consequently, the exposures decreased, both in
      terms of intensity and in terms of number of exposed workers but exposures will
      reach a complete end only when asbestos is completely cleared out. In this paper,
      data about industrial divisions at major risk, derived from the tuscanian cases,
      as well as the list of the jobs of the present asbestos exposed workers are
      illustrated.

PMID- 14582275
TI  - [Interaction between occupational and environmental exposure to asbestos.
      Epidemiologic survey].
AB  - In this short review we present the evidence of association of Malignant
      Mesothelioma and asbestos exposure in Italy, with focus on environmental
      exposure. After almost 10 years from the cessation of industrial use of asbestos,
      areas of high incidence attributable to environmental exposure are still
      observed.

PMID- 14582276
TI  - [Indications of public health in areas naturally polluted with asbestiform
      fibers].
AB  - Adverse health effects of naturally occurring asbestiform fibres have been
      reported since the Seventies in various countries. The present paper describes
      the case of Biancavilla, a municipality located in Eastern Sicily, where the
      occurrence of the amphibolic fibre fluoro-edenite has been associated to a
      cluster of pleural mesotheliomas. The public health recommendations aimed at
      reducing exposure to fluoroedenite are described. This case study shows the
      importance of public-driven remedial action, including interruption of activities
      of previously operating quarries and asphalt paving of roads, in influencing
      population's compliance to recommendations aimed at modifying individual
      behaviours. In order to pursue the goal of fostering community's autonomy in
      decision making, the optimal approach is ensuring timely and transparent
      information dissemination.

PMID- 14582277
TI  - [Three cases of pleural mesothelioma and environmental pollution with tremolite
      outcrops in Lucania].
AB  - In a circumscribed rural area of Lucania (Italy) three cases of pleural
      mesothelioma have been identified: two men, 83 and 52 years old and a 78 year-old
      woman, who all had in common the fact of being shepards in that area. Possible
      asbestos pollution sources have been sought: we have immediately excluded an
      asbestos manufactured articles pollution, however we have highlighted the
      presence of "green stones", which had always been known to the local inhabitants
      and which, in three subsequent campains of collecting and chemical-mineralogical
      investigations, have resulted partly constituted by amphibole asbestos,
      classified as tremolite. Official institutions are organising a series of
      initiatives to verify the hypothesis of a causal relationship between the
      presence of tremolite and the cases of pleural mesothelioma, and preventive
      initiatives aimed at reducing exposure and to a sanitary surveillance. Similar
      problems had been identified in Turkey, Greece, Corsica, New Caledonia and
      recently in eastern Sicily.

PMID- 14582278
TI  - [Epidemiology of radiation-induced tumors].
AB  - The radiation oncogenesis is a theme well defined from the nosological point of
      view by the "Evidence Based Medicine" (EBM) founded on sound scientific and on
      sound medical evidences. Radiobiology and radioepidemiology are the scientific
      and medical branches for this purpose. The very huge number of collected data
      analysed by numerous international and national scientific organisms (RERF, NIH,
      BEIR, ICRP, IARC, UNSCEAR) (1-9) can individuate the more susceptible organs and
      tissues to radiation cancer and the extent of their susceptibility by the
      evaluation of the relative risk related mainly to dose but also to other
      exposition parameters. So it is now possible to categorize many organs and
      tissues bearing in mind their specific susceptibility to cancer induction by
      ionising radiation. The author on the basis of the literature data propose a
      scale to categorize the interested organs and tissues in "very high", "high",
      "medium" and "low" steps of susceptibility to radiation cancer. The aim of this
      is to give an indicative aid to the occupational physicians actuating the medical
      surveillance on the radiation exposed workers.

PMID- 14582279
TI  - [Application of epidemiology to the protection of reproductive health].
AB  - The paper discusses the use of epidemiologic research for the prevention of
      occupational exposures focusing the hazards to the reproductive health of
      workers. For reproductive risks already documented in previous studies and in the
      available data, what is now needed is to identify better strategies to prevention
      rather than undertake further studies. Research is still needed however to
      identify risks previously not known and to investigate their mechanisms of
      action. This can be achieved by undertaking studies that measure with more
      accuracy the exposure of workers and examine the complex interaction of these
      exposures on the male and female endocrine system and on the fetus. One area of
      particular recent interest is that of the effects of the EDCs on human
      reproductive health, with results that confirm the interference of these
      chemicals on various reproductive outcomes in experimental animals and in humans.
      Other uses of epidemiologic research on human reproduction are related to
      establishing and updating the limits of environmental and occupational exposures
      and in providing reliable and unbiased information to workers and the public.

PMID- 14582280
TI  - [Analysis of occupational injuries using the new database developed for
      prevention in the workplace].
AB  - In Italy occupational injuries still represent a serious medical, social, and
      economic issue in spite of the improvement in working conditions, and an improved
      attention to occupational safety from both legislators and employers. In Apulia
      we have evaluated the new data record by INAIL (National Institute for Insurance
      against Occupational Injuries) reporting the occupational injuries occurred in
      2000 and compensated within the following year. The new data record represents a
      remarkable improvement, from the epidemiological point of view, compared to the
      old one. However, the statistical analysis is still not completely comparable to
      the international epidemiological indicators. Nevertheless, the coming data base
      will contain the first data codified in conformity with the new European
      recording system "ESAW/3" adopted by INAIL since January 1st 2002.

PMID- 14582281
TI  - [Retrospective estimate of occupations exposure to solvents. Methodology used in
      the Epilymph study].
AB  - To assess occupational exposure to solvents in the EPILYMPH multicentre case
      control study on lymphoma, we combined experts assessment, based on detailed
      description of work tasks from questionnaires, with the use of job-exposure
      matrices (jem). Whenever occupations and/or industries conveying exposure to
      occupational risk factors for lymphoma occur in their work history, the
      interviewer selects the respective questionnaire in a set of 15 special
      questionnaires and applies it to the study subject. All jobs lasting one year or
      more in the work histories are coded using the 1968 ILO ISCO, and the 1996 EEC
      Classification of Economic activities (NACE). A priori jems for 3 categories of
      solvents (solvents in general, chlorinated aliphatic hydrocarbons and benzene
      toluene-xylene combination) and 10 individual agents have been constructed based
      on the same coding systems, by which each occupationa/industry combination
      receives a unique score for confidence and intensity of exposure to each agent
      and group of solvents. Trained industrial hygienists (IH's) in each participating
      country examine the general and special questionnaires and classify three indices
      of exposure for each agent under scrutiny: confidence, which represents the IH
      degree of certainty that the worker has been exposed to the agent; frequency,
      which is expressed in a 4-step scale according to the proportion of working time
      involving contact with the agent; and intensity, which is also expressed in a
      scale, defined by quantitative cut-points, when available, or benchmark
      occupations, when no quantitative information is available from the
      questionnaires. The IH finally notes his degree of reliance on his own exposure
      estimate. The IH supports his exposure assessment with confidence and intensity
      scores provided by the jem when questionnaire information is so poor that it does
      not provide any clue about exposure, or he relies poorly on his own exposure
      estimate. Such a procedure is conceptually alike to statistical procedures to
      fill missing data in a given series.

PMID- 14582282
TI  - [Environmental pollution and short-term effects on human health in industrialized
      urban areas].
AB  - Several studies investigating the adverse short-term effects of air pollution
      indicate that even concentrations of air pollutants close to or lower than air
      quality standards could negatively affect respiratory and cardiovascular health.
      Therefore, it seems crucial to develop knowledge about health adverse effects in
      industrialized urban areas. A time-series study on the association between air
      pollution levels and daily mortality and hospital admissions for respiratory and
      cardiovascular diseases is currently carried out in the town of Taranto, "area at
      high environmental risk" according to WHO because of the presence of several
      heavy industries and elevated rates for all-causes and all cancer mortality,
      higher than regional mortality rates, especially for lung cancer.

PMID- 14582283
TI  - [Molecular epidemiology for the study of the environment-genome interaction].
AB  - The study of the gene-environment interaction considered initially genes involved
      in the biotransformation of carcinogenic agents. Genetic polymorphisms are useful
      markers of individual susceptibility, provided that their association with the
      exposure and the outcome of interest are clearly understood. The availability of
      biochemical and molecular markers in epidemiology research has been greeted as a
      major step forward from the traditional "black box" epidemiology, and certainly
      represents a real advancement in knowledge. Yet, the advancement in research made
      possible by the adoption of molecular biomarkers in epidemiological studies still
      needs to be evaluated as a relevant and effective tool for a more adequate
      prevention of the adverse effects caused by environmental agents.

PMID- 14582284
TI  - [Differences of mortality risk for all causes and for cardiovascular diseases
      among occupational classes in men living the Northern Italy].
AB  - To assess socio-occupational (SO) class differences in 8-year risk of all-cause
      and cardiovascular (CVD) death in an North Italian prospective epidemiological
      study, five cohorts (four population-based and one factory-based) were
      investigated at baseline from 1986 to 1995. Follow-up procedures allow to sensor
      4339 35-74 years old men up to the end of 1998 for all-cause and cardiovascular
      deaths. Coronary risk factors were measures according to the standardised methods
      of MONICA Project. Five SO classes were identified according to the method
      proposed by Erikson, Golthorpe e Portocarero. Results shows an inverse
      associations between SO classes and death risk for all-cause and cancer. The
      higher SO classes showed higher risk of cardiovascular death risk. Possible
      explanations include high level of job stress among employed managers and
      professionals.

PMID- 14582285
TI  - [African towns and health: references and stakes].
AB  - Urbanization is a fairly recent phenomenon. Thus during the 19th century, only 5%
      of the population was living in town. However it is more and more important as
      urban population has been multiplied by 15 since 1900. In Africa, this evolution
      is still more recent and the continent remains poorly urbanized. But the rate of
      urbanization is the fastest in the world and demographic forecasts indicate that
      by 2025, more than 50% of the African population will live in towns. Consequences
      of urbanization on human development are not well known. Concepts of demographic
      and epidemiological transitions were widely used for health. Health transition is
      another concept, including cultural, social and behavioural determining factors
      as well as ways of caring and being cared for. These processes account for the
      reduction of infectious diseases through a fall of mortality and birth rates and
      the emergence of non-transmissible diseases like cardiovascular diseases,
      cancers, mental diseases.... Although health situation is depicted as better in
      towns (better immunization, health care offer, better access to health care...),
      mortality and morbidity patterns seem to change more quickly in towns than in
      rural areas. However this is not true everywhere in urban areas where several
      towns are to be found within the same town and for example, health of populations
      living on margins may be worse than that of rural populations. Urban people
      resort to modern health care together with traditional healers, even informal,
      sometimes illegal health care, involving heavy costs but offering no guarantee as
      regards their quality and their efficiency for patients and society. It appears
      that developing countries have to face a new health care demand quite different
      from the one they used to face before, when they have simultaneously to cope with
      uncontrolled town growth. Under these conditions, urban health should become a
      priority.

PMID- 14582286
TI  - [Cyclospora cayetanensis presence in aquatic surroundings in Hanoi (Vietnam).
      Environmental study (well water, lakes and rivers)].
AB  - Cyclospora cayetanensis is a pathogenic agent originating from the intertropical
      zone. It causes diarrhoeal diseases in local populations as well as in travellers
      visiting these zones. In the first part of this work, an epidemiological study on
      drinking water supply (reservoirs and consumers' taps) was conducted in Hanoi
      over 12 months; samples were daily collected and have revealed the presence of
      Cyclospora cayetanensis oocysts during the whole year in tanks and only during
      monsoon season. Molecular methods were used for species identification. In the
      second part, we tried to investigate different water sources in Hanoi city in
      order to detect Cyclospora cayetanensis environmental contamination:
      groundwaters, surface waters collected in lakes and rivers and also waters from
      treatment plants. Our results show that none Cyclospora cayetanensis oocyst was
      found in the groundwaters and in the desinfected finished waters after treatment.
      In contrast, in rivers and lakes samples, the level of positivity reached about
      63.6% with significant differences between the districts regarding the rates of
      oocysts recovery: only 24% positive specimens in Hoan Kiem district, whilst
      respectively 80.4%, 78.3% and 65% positive samples in Hai Ba Trung, Dong Da and
      Ba Dinh districts. The results of this study seem to confirm that environmental
      water is contaminated by Cyclospora cayetanensis oocysts and points out the
      importance of water as a significant source of human transmission. It is quite
      obvious that observation could be probably extended to the other endemic areas.

PMID- 14582288
TI  - [Placental infection by Plasmodium falciparum in an urban area of Senegal].
AB  - OBJECTIVES: This study aimed at describing the burden of malaria at delivery in a
      urban maternity in Senegal. We measured the prevalence of placental malaria
      infection. We described the association between placental malaria and low birth
      weight and the impact of chemoprophylaxis. STUDY AREA: Guediawaye is the most
      important suburb of the city of Dakar, Senegal, surrounded by a permanent marsh
      (niayes). Malaria in this area is hypo endemic transmission: 1 infective
      bite/person/year. An. arabiensis is the principal vector and P. falciparum (98%)
      the most frequent species. The Maternite Roi Baudoin in Guediawaye is the
      gynecologic and obstetrical reference centre of this area with more than 6000
      deliveries/year. METHODS: We carried out an exhaustive survey from August 98 to
      December 99 at the maternite Roi Baudoin in Guediawaye. The socio-demographic
      data, the clinical data and information about prophylaxy were collected by
      questionnary. For each woman at delivery, one placental apposition was carried
      out. Presence of trophozoites or schizontes indicated malaria placental
      infection. RESULTS: 8310 women were included in the study. They were from 13 to
      49 years old with an average age of 26.1; 28% were primigravidae. The prevalence
      of placental malaria infection was 8.1% (674/8310) [Ic95: 7.4-8.8%]. Schizontes
      were present in 80.5% of infected placenta. The prevalence was 8.8% within
      primigravidae group and 7.4% in the other parity groups, p = 0.28 (NS). Placental
      infection was present all the year long. However, there were important seasonal
      variations. The risk of placental infection increased during seasonal
      transmission (> 10%) compared to the period of low transmission (3%). The
      prevalence of placental malaria was lower in the group of women who declares
      regular chloroquine intake compared with those who declared taking no prophylaxy
      or irregular prophylaxy (RR = 0.78 [0.62-0.98]). The risk of low birth weight was
      of 1.9 [1.6-2.1] when the placenta was infected compared with non infected
      placenta. CONCLUSION: This study indicates that placental malaria infection is
      frequent in this low transmission area where more than 70% of women declared
      taking regular chloroquine. This observation could be explained by a resistance
      of P. falciparum to chloroquine or a poor observance of chemoprophylaxis.

PMID- 14582287
TI  - [Pertinence of the 2000 WHO criteria in non-immune children with severe malaria
      in Dakar, Senegal ].
AB  - The relevance of World Health Organization (WHO) criteria for severe malaria has
      not been assessed in non-immune children. The objectives of this study were (i)
      to evaluate the significance of 1990 WHO definition reconsidered in 2000 on
      distribution and lethality of severe cases in children admitted with falciparum
      malaria, and (ii) to contribute to the study of relevance of the WHO severe
      criteria in Dakar, an hypoendemic area in Senegal. PATIENTS AND METHODS: The 1990
      WHO criteria, respiratory distress and platelet counts were prospectively
      collected in 1997-99 from children admitted to Hopital Principal de Dakar,
      Senegal, with falciparum malaria diagnosed on a thick blood film. This method
      allowed also the definition of severe cases according to 2000 WHO criteria.
      RESULTS: Among 311 patients (median age: 8 years old), according to the 2000 WHO
      criteria, the frequency of severe malaria cases was increased by 23% (75% versus
      52%) and case-fatality rates thereof were decreased by 5% (17% versus 12%)
      compared with 1990 WHO definition. One death occurred among cases defined as
      severe on admission only according to criteria modified by WHO in 2000. A
      multivariate logistic regression model identified several independent prognostic
      factors: cerebral malaria, hypoglycaemia, respiratory distress, renal failure,
      collapse, abnormal bleedings, pupillary abnormalities and thrombocytopaenia
      defined as a platelet count below 100,000/mm3. A significant association (p <
      0.001) was observed between platelet count increase and consciousness level
      improvement, evaluated on day of first platelet count control (time from
      admission: 1-7 d). Among survivors, a lesser improvement in coma score was
      associated with a decrease in platelet counts (p < 0.04). CONCLUSIONS: The 1990
      WHO criteria, which predicted death among malaria cases in children living under
      stable falciparum transmission, are relevant in this series of non-immune
      children living in a low and seasonal transmission. Nevertheless new WHO criteria
      showed poor prognostic significance. However, the 2000 WHO definition was highly
      sensitive to detect severe malaria cases. These findings should be considered for
      managing severe malaria in migrant children.

PMID- 14582289
TI  - [Development of a PCR (polymerase chain reaction) specific for complex Anopheles
      nili (Theobald) 1904 species in Cameroon ].
AB  - The objective of this study was to develop new molecular tools for the
      identification of members of An. nili group, a malaria vector in Africa. Our
      strategy was based on the sequence analysis of portions of the rDNA. The ITS2
      fragment of An. nili collected in Cameroon was sequenced and compared. The
      analysis of these sequences has revealed a great variability of ITS2 sequence.
      Three molecular forms: An. nili typical form, An. nili Oveng form and An.
      carnevalei were observed within the six morphological types. Specific primers
      were selected on ITS2 sequence to develop an allele-specific PCR giving 3 size
      bands. 169 specimens of An. nili collected in Cameroon were successfully tested.
      This method has been validated on specimens collected in others localities of
      tropical Africa. The multiplex PCR developed was very sensitive practical and
      applicable on large scale.

PMID- 14582290
TI  - [Course of urinary schistosomiasis in Niamey, Niger].
AB  - A school survey has been carried out in 1998 on a representative sample of 30
      schools to assess the effect of the recent urban growth of Niamey on the urban
      focus of urinary schistosomiasis. A total of 2,024 10-12 years old children were
      examined and questioned about their water contacts in Niamey and travels in rural
      areas during the previous year. Generally the prevalence of S. haematobium was
      low (16%). This can be explained by the lower exposure in urban areas; by the
      moderate transmission level in the river and by the low incidence of temporary
      stays in rural areas. A second survey has been carried out in 2000 in 4 schools
      of a periurban suburb to study the distribution of parasitological risk at the
      periphery level. A total of 247 10-12 years old children were examined and
      questioned about their water contacts. Prevalence of S. haematobium was higher in
      this suburb (74%) but there was a significant decrease of parasitological indices
      from periphery to the centre. This change seemed related to differences of
      exposure with an increasing use of water supply and a decreasing use of
      irrigation canals for swimming and domestic activities.

PMID- 14582292
TI  - [Schistosomiasis due to Schistosoma intercalatum and urbanization in central
      Africa].
AB  - The species name of Schistosoma intercalatum, Fischer 1934 is linked to the shape
      and the size of his eggs, which are intermediate between those of S. haematobium
      and S. bovis. S. intercalatum is the instrument of an intestinal form of
      schistosomiasis looking like the form induced by S. mansoni but characterized by
      a low location of the lesions, mainly situated at the rectum and sigmoid level.
      The spreading area of S. intercalatum is bound to Central Africa. The foci are
      often urban and of a size limited to a town district. Bulinus forskalii is the
      intermediate host mostly involved in transmitting S. intercalatum lower Guinea
      strain, which is the strain found in the largest number of foci. B. crystallinus
      too transmits the parasite in the area of Gamba in Gabon. The Central Basin
      congolese strain of S. intercalatum is transmitted by Bulinus globosus. The
      houses where inhabitants are voiding eggs of S. intercalatum are just in front of
      the river bank or stream which are snails'breeding places. S. intercalatum is
      expending at the present time because of the development of built-up areas which
      are characterized by a disorganized town-planning. The disease is due to the high
      faecal pollution of the environment, causing a contamination of the urban
      hydrographic network which is the setting of schistosomiasis transmission.
      Although primely linked to the forest area, S. intercalatum is spreading with
      deforestation. Coming from the savannah area, S. haematobium is now invading the
      forest area, entering into competition with S. intercalatum. But since Bulinus
      acting as intermediate hosts of S. haematobium are more heliophilous than Bulinus
      transmitting S. intercalatum, urinary schistosomiasis has a tendency to supplant
      recto-sigmoidal schistosomiasis, especially in foci where hybridization between
      the two species of schistosomes is occurring.

PMID- 14582291
TI  - [Transmission of Schistosoma haematobium in the town of Niamey, Niger].
AB  - Located in an area where Schistosoma haematobium is hyperendemic, the town of
      Niamey is a focus of hypoendemicity. The aim of the malacological follow-up
      studies undertaken over a one year period was the determination of the mollusc
      species present in the water bodies, the appreciation of their space-time
      distribution of the snail and to find out the potential seasons of transmission.
      The investigation applied to 22 sites of transmission in the urban community.
      Four molluscs species (Bulinus truncatus, B. forskalii, B. globosus and B.
      senegalensis) are collected. The first three species are present all the year
      long, with a peak of density in the dry season. The last species (B.
      senegalensis) is found only during the rainy season. B truncatus and B.
      senegalensis are the two naturally infested species. The main site of
      transmission is the river Niger. The ponds play a secondary role in the
      peripheral districts. The main intermediate host of S. haematobium is B.
      truncatus.

PMID- 14582293
TI  - [Transmission of schistosomiasis in an urban population and prevalence of
      intestinal helminthiasis in Bamako, Mali ].
AB  - Parasitological, malacological and anthropological studies were performed to
      assess the prevalence of Schistosoma haematobium and S. mansoni in schoolchildren
      living in the suburban area of Bamako. A total of 1017 schoolchildren aged 6-14
      years were selected in two different areas between September 1997 and December
      1999. In Djikoroni, the prevalence of S. haematobium and S. mansoni was 80.7%
      (339/420) and 22.8% (85/372) respectively. There was no significant difference of
      prevalence and intensity of infection with S. haematobium between schools, gender
      and age (p > 0.05), whereas, those of S. mansoni were higher in the vicinity of
      (+/- 100 m from) major sites where infected Biomphalaria pfeifferi were found (p
      < 0.001). In Niomirambougou, S. haematobium was prevalent in 46.7% (279/597) and
      S. mansoni in 28.2% (134/475). Boys and children aged 11-14 years were more
      infected (p < 0.001). Associated intestinal helminths (Hymenolepis nana, Necator
      americanus and Ascaris lumbricoides) were relatively scarce (prevalence < 1%).
      The prevalences of schistosome infected snails intermediate host were relatively
      high, 49.3% (100/203) in B. pfeifferi, 20.6% (88/138) in B. truncatus and 24.1%
      (7/29) in B. globosus. We recorded a total of 2514 water contacts about which
      1130 in December and 1384 in January. Most of the children, 42.9% (1077/2511)
      were attracted to water bodies for bathing, swimming and playing, suggesting the
      lack of recreational facilities in these areas. Developing local control
      programmes in schools located in the vicinity of water bodies would contribute to
      break the parasite transmission cycle in Bamako.

PMID- 14582294
TI  - [Portal hypertension and schistosomiasis: "an originally killing entity"].
AB  - In some regions of Africa, Middle-east and Asia, portal hypertension is caused
      most frequently by bilharziasis far more than by post-hepatic or alcoholic
      cirrhosis. All schistosomiasis induce hepatic affection, consequence of the eggs
      embolization in the vessels endings of the portal system, but only Schistosoma
      mansoni and Asian bilharziasis mainly the Schistosoma japonicum are the cause of
      severe sequelar fibrosis responsible for a particular portal hypertension. This
      portal hypertension is original anatomopathologically and physiopathologically.
      The perivascular concentric fibrosis localised in the portal space is an
      anatomopathological sequela of bilharzious granulomas outlining embolized eggs.
      This "stem pipe" aspect constitutes a presinusoidal block inducing a severe
      portal hypertension without hepatic lobule affection. The recent medical advances
      regarding this pathology lie in the understanding of the responsible immune
      mechanisms, the diagnosis and follow-up thanks to ecographic codification of
      lesions, the complications treatment through varix endoscopic ligature or portal
      vein derivation. Treatment by praziquantel remains justified together with health
      education, improving living standard and hopes placed in the future vaccination
      campaigns associated with medical treatment in endemic areas.

PMID- 14582295
TI  - [Decompensated post-schistosomiasis portal hypertension in Richard-Toll, Senegal:
      first case treated by splenorenal anastomosis in Dakar].
AB  - Since the Diama dam on the Senegal river became operative in 1986, an exceptional
      outbreak of intestinal schistosomiasis occurred in northern Senegal. This is the
      first case report from this region of a splenorenal derivation performed in Dakar
      to cure decompensated portal hypertension due to Schistosoma mansoni. CASE
      REPORT: In June 1998, a 16-year old boy, native from Richard-Toll in the Senegal
      River Basin, was admitted to the paediatric department of Hopital Principal,
      Dakar, Senegal, with a 3 years of recurrent hematemesis. Blood transfusions were
      required despite propranolol and multiple oesophageal varices sclerotherapies. On
      admission he weighed 33 kg and was noted to have pallor and moderate
      hepatosplenomegaly. Lab work included normal liver function tests, a Hgb of 58
      mg/L, negative HBs antigen, and high titers of schistosomiasis antibodies (>
      1/2000 by the hemagglutination method). Ultrasound revealed an homogeneously
      enlarged liver, periportal fibrosis and spleen with a grade 2 portal hypertension
      (WHO score). Endoscopy showed stage 3 oesophageal varices with red spots but no
      active haemorrhage. After transfusions, a Warren distal splenorenal anastomosis
      was performed. During the operation, a liver biopsy was obtained, showing
      periportal fibrosis and schistosomiasis granulomas. The patient was discharged
      without complication. After 4 years he remains free of any recurrence of his
      upper gastrointestinal haemorrhage and haemoglobin rate is normal. COMMENTS:
      Before the inauguration of the dam in 1986, S. mansoni infection was never
      reported from the Senegal River Basin. But as early as 1988, the first cases of
      intestinal schistosomiasis began to show up. A few years later, this focus had
      dramatically extended and in 1991 the first cases of hepatic fibrosis were
      detected in ultrasonography surveys. The present case involves the first patient
      from northern Senegal who required surgery for haemorrhagic complications of
      schistosomiasis induced by liver disease. Considering the high prevalence in this
      area, and the difficulties of medical management, the need for porto-systemic
      derivations is likely to rise. These operations are difficult and require
      specially trained surgeons. They have been largely unavailable in Senegal until
      now. This case report, involving a child only 10 years after the beginning of the
      epidemic, underlines the acute need for improving both prevention and medical
      treatment in order to avoid progression to clinical stages of hepatic
      schistosomiasis where surgery is unavoidable. In addition, the training of local
      surgical teams able to deal with these complications is urgently needed in
      Senegal.

PMID- 14582296
TI  - [Human African trypanosomiasis in an urban area: an emerging problem?].
AB  - The human African trypanosomiasis is essentially a rural disease. The
      notification of cases in urban area has always been incidental; either a
      diagnosis made in town revealed a disease contracted in rural environment or it
      meant the preservation of a complete epidemiological cycle in a remaining urban
      micro-focus. In Kinshasa, in Democratic Republic of Congo, about forty cases have
      been notified each year. All of them came from the nearby foci of Bandundu, Lower
      Congo and Kasai. In 1996 the number of cases reached suddenly 254 and today the
      average annual number comes up to 500 in spite of all the efforts undertaken to
      fight the disease. A study of cases in 1998 and 1999 shows that patients are
      essentially distributed in suburbs and that the most affected by the disease are
      the 15-49 year old ones whose job is related with agricultural or fishing
      activities. Two phenomena seem to explain this sudden increase: the massive
      inflow of refugees in outskirts of town coming from provinces where
      trypanosomiasis is endemic and a major economic crisis throwing out urban
      population in suburbs living on a subsistence micro-agriculture. These
      concomitant factors have contributed to the setting up of a trypanosomiasis belt
      around the capital. Today a strategy has to be reconsidered in order to fight
      against the disease in the capital itself and to make the medical staff aware of
      the diagnosis of a disease still unknown in their sanitary district.

PMID- 14582297
TI  - [Liposomal amphotericin B treatment of cutaneous leishmaniasis contracted in
      Djibouti and resistant to meglumine antimoniate].
AB  - Pentavalent antimony (PA) compounds remain the main therapeutic agents of
      cutaneous leishmaniasis (CL). CL infection resistant to PA is difficult to cure,
      limited by severe side effects and requiring a long course treatment of
      parenteral administration of recommended second line drugs. We report a case of
      CL unresponsive to meglumine antimoniate contracted in Djibouti, successfully
      treated with a short course treatment of AmBisome. In this case the subject had a
      recurrent thick crusted erythematous lesion on his left elbow associated with
      spreading micropapula on arms and thorax. The diagnosis of CL was confirmed by
      direct examination and genomic amplification by PCR of skin samples, cultures
      were negative. A short course treatment of parenteral AmBisome (18 mg/kg) has
      lead to clinical cure with no side effects and no relapse. In our hospital, the
      high cost of medication was counterbalanced by easiest administration, reduction
      of hospitalization duration, absence of adverse events and a gain of comfort. For
      this patient, a short course treatment of AmBisome proved to be a suitable
      alternative to traditional drugs used in CL resistant to PA.

PMID- 14582298
TI  - [Leishmaniasis in Algiers: epidemiologic data].
AB  - The authors review the situation on human and canine leishmaniasis observed in
      Algiers during the period 1990-1997. 1800 sera have been tested by IFAT. The
      frequency of canine leishmaniasis rises to 37%. 25% of the positive dogs are
      asymptomatic. The canine leishmaniasis annual fluctuations seem to vary from one
      year to another, with an increase of number of cases comparing with the last
      period. Human leishmaniasis is also increasing in Algiers, where 22 cases of HVL
      and 40 cases CL have been notified. Nine strains of Leishmania (5 from dogs and 4
      from human) were isolated and identified by isoenzymes eletrophoresis technique.
      All stocks were belonging to Leishmania infantum complex. To complete the study,
      the seasonal dynamic of phlebotomine sandflies was carried out in the same area
      where 2959 specimens have been captured. The results showed the predominance of
      P. perniciosus and P. longicuspis, the main vectors of visceral leishmaniasis in
      Algeria.

PMID- 14582300
TI  - [Knowledge of an urban population about arterial hypertension: prospective study
      carried out in Ouagadougou, Burkina Faso].
AB  - The objective of this prospective survey was to estimate the prevalence of
      hypertension in the city of Ouagadougou and to evaluate the information level as
      well as the knowledge of the population regarding hypertension. We carried out a
      urban community based cross sectional study. Subjects were black African, and
      aged of 18 years at least. They were considered hypertensive when they were under
      a treatment for hypertension, or when they had high blood pressure (> or = 140/90
      mm Hg) according to the WHO classification in 1999. The study selected 3441
      subjects, among them 60.4% of women and 39.6% of men. The average age in the
      sample was 33.1 +/- 13.3 years; 64.4% of the subjects were 20 to 40 years old.
      The average systolic blood pressure in the population was of 124 +/- 21 mm Hg,
      and of 78 +/- 12 mm Hg for the diastolic one. The prevalence of hypertension in
      our sample was 23%, with 20.4% of unknown hypertensive subjects. Hypertension is
      highly frequent in urban area in Burkina Faso. As it could be expected, the
      knowledge of the population regarding hypertension proved inversely proportional
      to the educational level. Information programs and consciousness-raising campaign
      as well as detection program should be implemented urgently.

PMID- 14582299
TI  - [Cardiac insufficiency in the African cardiology milieu].
AB  - OBJECTIVE: The aim of this study is to determine the frequency, the aetiologies
      and the hospital mortality of heart failure in African developing countries.
      METHODS: A prospective study rolled over six months in African urban hospital
      including 170 patients, middle age 50 years old suffering from heart failure.
      They underwent clinical, paraclinical cardiac examination. RESULTS: Heart failure
      represented 37.7%. Main cardiac failure risks were: hypertension: 76 cases (45%),
      diabetes mellitus: 20 cases (11.8%). General heart failure is noted at the
      entrance in 67.6% with cerebral attack in 5%. EKG showed left ventricle
      hypertrophy in 108 patients (63.5%) and atrial fibrillation in 28 patients
      (16.6%). Valvular heart diseases and hypertension are the main aetiologies
      respectively: 76 cases (45%) and 58 cases (34%). In 10 cases (6%) the aetiology
      is unspecified. Hospital mortality concerned 44 patients (25.9%). CONCLUSION:
      Heart failure is grave and frequent in developing countries where there is no
      cardiac surgery. Prevention is possible: fighting against articular rheumatism
      and control hypertension.

PMID- 14582301
TI  - [Influence of urban migration on physical activity, nutritional status and growth
      of Senegalese adolescents of rural origin].
AB  - In Africa, rural populations especially adolescent girls resort to urban
      migrations for labour in order to diversify and improve their livelihood. Their
      work and their living conditions may influence their health and development
      patterns. The aim of this study was to evaluate the influence of these migrations
      on physical activity, nutritional and growth status of rural Senegalese
      adolescent girls. In 1998, within the framework of a longitudinal study of growth
      during puberty (n = 406), a sub-sample (n = 80, 14.4 +/- 0.5 years) was drawn in
      order to estimate physical activity, during three days, quantitatively by
      accelerometry and qualitatively by questionnaire. One part of this sample
      temporarily migrated to Dakar in order to work as maids (migrants, n = 40). The
      other part remained in the rural community of Niakhar in order to help their
      families in daily domestic and agricultural tasks and/or to attend school (non
      migrants, n = 40). In 1999, sexual maturation of 331 adolescent girls (15.5 +/-
      0.5 years) belonging to this group was based on stages of breast development and
      occurrence of menarche. Their growth and nutritional status were assessed with
      anthropometry (height, weight, mid arm circumference, six skinfolds). Adolescents
      were asked about their urban migratory histories and were divided into four
      categories according to the duration of urban migration: no migration (NM), short
      (S), medium (M) and long duration (L). These adolescent girls had a very high
      physical activity which is far higher than that of American girls. Migrants were
      more active than non-migrants (p < 0.0001). In 1999, as a whole, these 331
      adolescent girls were smaller, thinner and less mature than adolescent girls from
      industrialized countries. Midarm circumference, body mass index (BMI) and fat
      mass index (FMI) were significantly higher with the duration of migration (p <
      0.01), after adjusting for differences in sexual maturation. Growth retardation
      seemed more important for the adolescent girls who never migrated and for those
      who have the longest duration of migration (p = 0.05). At the beginning of
      puberty, there were no differences in height for age indice and BMI. Urban
      migrations resulted in an advanced puberty and an improvement of nutritional
      status (higher BMI, FMI and midarm circumference) but without catch-up in growth.
      These findings could be explained by precarious living conditions in rural area
      and by higher workload in urban area.

PMID- 14582302
TI  - [Prevalence of HIV in Mayotte].
AB  - Mayotte is a little French island, located in the Indian ocean, between
      Madagascar and Mozambic. Officially, the population goes up to 150,000
      inhabitants, but in fact, it probably comes up to about 200,000 people, because
      of a very numerous illegal immigration, especially coming from Anjouan, the
      nearest Comorian island. Up to now there are no data about HIV in Mayotte. There
      is only one adult medical unit (except intensive care). All patients detected as
      seropositive for HIV are sent for treatment in this unit. The only case of
      systematically proposed HIV serology is pregnancy, and this since 1994. 70% to
      80% of women accept it. There are annually 6000 deliveries in Mayotte. When a
      seropositivity is detected, screening is systematically proposed to other members
      of the family. Epidemiology does not seem to worsen, even if detection is
      increasing: 8675 tests done in 1998, 9142 in 1999, 12,085 in 2000. All cases of
      seropositivity attended to at present time in our unit have been registered and
      studied, apart from patients who died before this study, and those who did not
      consult for more than two years. There were 8 HIV positive people who died since
      1990 in Mayotte, most of them in 1991, 1992. There was no death in the last
      years, nor sanitary evacuation, except one. 50 people are registered: 20 males,
      30 females. Average age is 34. 39 Comorian people, 10 metropolitans, and one from
      another origin. Contamination was heterosexual in 43 cases, intravenous drug user
      in 1 case, homosexual in 2 cases, professional in 1 case, unknown in 3 cases.
      There are 4 double contamination Ag Hbs/HIV, and 2 HCV/HIV. 39 subjects are at A
      stage, 5 B, 6 C. The beginning of the epidemic in Mayotte took place probably
      around 1990, among militaries and prostitutes. Now, transmission keeps going on,
      in most cases, heterosexual, as it occurs in the nearby Africa. Polygamy,
      official or officious, has a leading role. Females who were detected during
      pregnancy have obtained zidovudine, or have been able to pursue previous therapy.
      Medical care and therapy are free in Mayotte, but sometimes there are delays in
      supplying medicines or in returning results. Epidemic has not increased up to
      now; even though screening has. There are very few pediatric cases: only 4 cases
      were notified in Mayotte until now: one who died very soon, one who has gone to
      live in Reunion island, and two who are still in Mayotte: one is 12 years old,
      and another one 5 years old.

PMID- 14582303
TI  - [Free dispensing of antiretroviral treatments in Africa].
AB  - The bio-clinical efficacy of ART in Africa has now been proven. In 2001, the
      resolution adopted by the UNGASS meeting confirms that "effective prevention,
      care and treatment strategies will require [...] a non-discriminatory access to
      [...] anti-retroviral therapies". Most of the programmes that give access to ART
      initiated in the sub-Saharan region in 1998 are based on the principle that the
      patients participate financially to the purchases of ART. Some countries (Cote
      d'Ivoire, Senegal, and Mali) subsidize ART medications to favour a better access.
      The financial contribution of patients is supposed to: 1/ translate patient
      support into government action; 2/ favour a closer therapeutic adherence; 3/
      assure the access programmes sustainability. However, despite the subsidies
      provided by some states, the cost of medical treatment greatly exceeds the
      resources available to most of the sufferers. The analysis of ART access
      programmes, specifically in Senegal and Cote d'Ivoire, shows that: 1/ Patient
      support to government action does not need to be more demonstrated while general
      access to treatment is officially recognised and recommended by the United
      Nations. 2/ Patient involvement and better adherence have been noted with
      patients that receive free ART. 3/ Patient contribution represents less than 10%
      of the medication's purchasing cost, thus, the cost recovery is marginal and does
      not allow for sustainable ART access programmes. The cost charged to patients for
      ARV still represents a major obstacle for proper medical management. Care
      programmes in African countries should implement free access to ART as a
      priority.

PMID- 14582304
TI  - [Centenary of the discovery of yellow fever virus and its transmission by a
      mosquito (Cuba 1900-1901)].
AB  - During the 17th, 18th and 19th centuries, yellow fever has been an ordinary
      scourge in American cities. In the early part of the 20th century, a main
      discovery has been achieved in Havana city, Cuba, leading to direct consequences
      for tropical medicine, public health and virology. There, the U.S. Army yellow
      fever commission headed by Walter Reed proved that yellow fever was a viral
      disease transmitted by a specific mosquito, Stegomyia fasciata, in fact Aedes
      aegypti L. The idea that vomito negro would be spread by mosquito bites was not a
      new one. It has already been postulated, since 1881, by Carlos Finlay, a Cuban
      physician, who has attempted to prove experimentally his hypothesis in human
      beings, but without real success. The U.S. Army commission quickly demonstrated
      two essential facts ignored by C. Finlay, which explained his failure. To be able
      to transmit yellow fever, Ae. aegypti had to bite a patient during the first
      three days of the disease (viraemia), and then, a delay of about 12 days was
      necessary before the mosquito would be ready to transmit the disease to a non
      immune human (the virus replication time inside the insect). Since the role of
      mosquito in spreading yellow fever was established, an efficient means to fight
      the scourge was available, i.e., the mosquito extermination. This concept was
      quickly applied leading to the complete clean up of Cuba (1901) and the Panama
      isthmus (1907).

PMID- 14582306
TI  - Racial differences in DSM diagnosis using a semi-structured instrument: the
      importance of clinical judgment in the diagnosis of African Americans.
AB  - Schizophrenia is diagnosed more frequently among African Americans while mood
      disorders are identified more often among whites. Such findings have raised
      serious questions about the accuracy of clinical judgment. This article analyzes
      data on 665 African American and white psychiatric inpatients using a semi
      structured diagnostic instrument. The paper explores the relationship of patient
      race to schizophrenia, schizoaffective disorder, major depression, and bipolar
      disorder. The paper also explores the extent to which patient race is related to
      the manner in which clinicians link individual symptoms to diagnoses. Results
      indicate some significant race differences in diagnosis remain even when a semi
      structured instrument and DSM criteria are used, whites, were more likely than
      African Americans to receive a diagnosis of bipolar disorder and less likely to
      be diagnosed with schizophrenia. There were no race differences in major
      depression. Some patterns of symptom attribution differed by race. The results
      are consistent with previous sociological research showing that patient race is
      related to diagnosis even when standardized diagnostic criteria are used. These
      findings underscore the importance of clinical judgment within the context of
      cross-race and cross-ethnic diagnosis. Clinical training programs must reduce
      ethnocentric bias by teaching the appropriate use of the socio-cultural
      information necessary to employ DSM-IV's Cultural Formulation.

PMID- 14582307
TI  - Rethinking a universal framework in the psychiatric symptom-disorder
      relationship.
AB  - Research on disparities in health and services should include a critical
      examination of how social, cultural, and contextual factors affect the connection
      between symptoms and psychiatric disorders. Systematic differences in this
      connection by these factors will mean that clinicians using a universalist
      approach to disorders may make more diagnostic errors for certain patients (e.g.,
      ethnic minorities, the poor). Based on the literature on normative clinical
      decision-making, this study tests for whether the effect of specific psychiatric
      disorders on key symptoms is the same for certain groups of the population. The
      data come from the National Comorbidity Survey. Conditional probabilities of
      disorders and symptoms, the elements feeding into clinical decision-making, are
      calculated and tested for equivalence across various racial/ethnic, educational,
      income, and gender groups. We find some significant differences in the relation
      of key symptoms to disorders across groups. These findings should encourage
      testing relativistic frameworks in diagnostic nosology as a step to improve
      clinical decision-making and reduce diagnostic and treatment disparities in
      mental health services.

PMID- 14582308
TI  - Status inequalities, perceived discrimination, and eudaimonic well-being: do the
      challenges of minority life hone purpose and growth?
AB  - Considerable prior research has investigated links between racial/ethnic status
      and diverse aspects of mental functioning (e.g. psychological disorders, quality
      of life, self-esteem), but little work has probed the connections between
      minority status and eudaimonic well-being. Derived from existential and
      humanistic perspectives, eudaimonia describes engagement in life challenges and
      is operationalized with assessments of purpose in life, personal growth,
      autonomy, environmental mastery, self-acceptance, and positive relations with
      others. Using Midlife in the United States (MIDUS), a national survey of
      Americans aged 25-74, plus city-specific samples of African Americans in New York
      City and Mexican Americans in Chicago, minority status was found to be a positive
      predictor of eudaimonic well-being, underscoring themes of psychological strength
      in the face of race-related adversity. Perceived discrimination was found to be a
      negative predictor of eudaimonic well-being, although such effects were gender
      specific: it was women, both majority and minority, with high levels of
      discrimination in their daily lives whose sense of growth, mastery, autonomy, and
      self-acceptance was compromised.

PMID- 14582309
TI  - Critical race theory speaks to the sociology of mental health: mental health
      problems produced by racial stratification.
AB  - The sociology of mental health focuses on the epidemiology, etiology, correlates,
      and consequences of mental health (i.e., psychiatric disorder and symptoms,
      psychological distress, and subjective well-being) in an attempt to describe and
      explain how social structure influences an individual's psychological health.
      Critical race theory describes and explains iterative ways in which race is
      socially constructed across micro- and macro-levels, and how it determines life
      chances implicating the mundane and extraordinary in the continuance of racial
      stratification (i.e., racism). This paper invoked critical race theory to inform
      the sociology of mental health's approach to studying race and mental health by
      conceptualizing five hypothetical mental health problems that could exist because
      of racial stratification. These problems were: (1) nihilistic tendencies, (2)
      anti-self issues, (3) suppressed anger expression, (4) delusional denial
      tendencies, and (5) extreme racial paranoia. Mental health problems such as these
      and undocumented others can only be recognized given awareness of the social and
      personal implications of racial stratification.

PMID- 14582310
TI  - Racial identity, racial discrimination, perceived stress, and psychological
      distress among African American young adults.
AB  - This study examines the direct and indirect relationships among racial identity,
      racial discrimination, perceived stress, and psychological distress in a sample
      of 555 African American young adults. A prospective study design was used to
      assess the influence of two dimensions of racial identity attitudes (i.e.,
      centrality and public regard) on other study variables to investigate the
      relationship between racial identity attitudes and psychological distress. The
      results show some evidence of a direct relationship between racial centrality and
      psychological distress, as well as evidence of indirect relationships for both
      centrality and public regard through the impact of racial discrimination and
      perceived stress. In addition, racial centrality was both a risk factor for
      experiencing discrimination and a protective factor in buffering the negative
      impact of discrimination on psychological distress. Results are discussed within
      the context of identifying multiple pathways to psychological well-being for
      African American young adults within the context of racial discrimination.

PMID- 14582311
TI  - Coping with perceived discrimination: does ethnic identity protect mental health?
AB  - Using data (N = 2,109) from a large-scale epidemiological study of Filipino
      Americans, this study examines whether ethnic identity is linked to mental health
      and reduces the stress of discrimination. The strength of identification with an
      ethnic group is found to be directly associated with fewer depressive symptoms.
      In other words, having a sense of ethnic pride, involvement in ethinic practices,
      and cultural commitment to one's racial/ethnic group may protect mental health.
      Self-reports of racial/ethnic discrimination over a lifetime and everyday
      discrimination in the past month not due to race/ethnicity are associated with
      increased levels of depressive symptoms. Yet ethnic identity buffers the stress
      of racial/ethnic discrimination. This suggests that ethnic identity is a coping
      resource for racial/ethnic minorities that should not be overlooked. The strong
      link between ethnic identity and better mental health has implications for social
      psychological theories on race/ethnicity and assimilation in the United States.

PMID- 14582312
TI  - The social psychological costs of racial segmentation in the workplace: a study
      of African Americans' well-being.
AB  - Although several studies have documented how social-structural constraints impair
      psychological functioning, few have considered how race-related structural
      constraints impair African Americans' psychological functioning. This study
      focuses on an under-studied form of race-related structural constraints: racial
      segmentation in the workplace. Specifically, I examine the association between
      perceived workplace racial segmentation, conceived and assessed from a social
      psychological perspective, and African Americans' psychological well-being. The
      magnitude and consistency of the relationship is evaluated across both a national
      sample and a local probability sample of African Americans. Findings across the
      two samples indicate a modest but consistent negative relationship between
      perceived racial segmentation and psychological well-being. In addition, this
      association remains significant after controlling for perceived discrimination as
      well as sociodemographic and occupational characteristics. Consistent with prior
      research on relative deprivation, the adverse influence of perceived racial
      segmentation on well-being was stronger among higher socioeconomic status African
      Americans than lower socioeconomic African Americans.

PMID- 14582313
TI  - Race differences in depressive symptoms: a dynamic perspective on stress exposure
      and vulnerability.
AB  - The existence, nature, and strength of race differences in mental health remain
      unclear after several decades of research. In this research, we examine black
      white differences in the relationship between acute stressors and depressive
      symptoms. We reframe the stress exposure and differential vulnerability
      hypotheses in the context of long-term trajectories of stress and depression, and
      we hypothesize that trajectories of stress growth will be associated with
      trajectories of depressive symptom growth. Using latent growth curve analysis of
      a sample of 1,972 older persons interviewed three times at three-year intervals,
      we test the hypotheses that (1) growth in exposure to loss-related events will
      predict growth in depressive symptoms, and (2) African Americans will experience
      greater stress growth than whites. Results support the hypotheses. Stress growth
      exhibited a linear increase for blacks but not for whites, and predicted
      depression growth for both races, but explained more variance for blacks than for
      whites.

PMID- 14582314
TI  - Race and ethnic differences in depressed mood following the transition from high
      school.
AB  - Young adulthood is a period of increased mental health risk, with evidence
      linking psychological disorder to problematic role transitions. To our knowledge,
      there has been little or no research that examines the forces shaping minority
      mental health at this time. Using a diverse, urban sample of young adults who are
      followed over a two-year period, this paper examines the link between
      race/ethnicity and depressed mood and the transitional roles and interpersonal
      experiences that mediate this association. Findings indicate that blacks and
      Hispanics have elevated depressed mood relative to whites and Asian Americans,
      independent of socioeconomic background factors. The underrepresentation of
      blacks and Hispanics in four-year colleges largely explains the differences in
      depressed mood between members of these groups and Asian American youth. In
      contrast, comparisons of black and Hispanic youth to white youth highlight
      problems in peer and parental relations among individuals in the former groups.
      Overall, findings suggest that the heightened depressed mood among Hispanics and
      blacks relative to whites and Asian Americans reflects their increasingly
      disadvantaged pathways into adulthood, characterized by poorer prospects for
      educational advancement and more problematic relationships subsequent to the high
      school years.

PMID- 14582315
TI  - Psychological distress among black and white Americans: differential effects of
      social support, negative interaction and personal control.
AB  - This study examines the relationships among social support, negative interaction,
      financial strain, traumatic events, personal control, personality, and
      psychological distress among African American and white adults. These analyses:
      (1) test the overall adequacy of various models (i.e., main, mediator, and
      artifactual effects) of these effects, (2) examine the role of social support and
      negative interaction within the context of financial strain and traumatic events,
      and (3) verify possible indirect effects of social interaction on distress by
      assessing their impact on personal control. Data from The National Comorbidity
      Survey were used to examine these relationships using structural equation
      modeling techniques. Findings indicated different models of these relationships
      for African Americans and whites. Overall, personal control mediated the
      relationship between negative interaction and psychological distress. For whites,
      negative interaction was an overall stronger predictor of distress and
      contributed to the impact of financial strain and traumatic events on
      psychological distress. Among African Americans, social support was a stronger
      predictor of distress. The findings suggest that the underlying models of these
      relationships are different for African Americans and whites.

PMID- 14582316
TI  - Problem drinking patterns among African Americans: the impacts of reports of
      discrimination, perceptions of prejudice, and "risky" coping strategies.
AB  - This research builds on a series of recent studies that have reported independent
      effects of personal experiences of racial discrimination on poor mental health
      outcomes. We suggest that for one mental health outcome, problem drinking,
      discrimination experiences have an impact not only via abridged socioeconomic
      attainment and the frustrations associated with institutionally limited
      opportunity structures, but also by directly increasing the likelihood of problem
      drinking. Moreover, we argue that personal experiences with discrimination help
      to foster a set of beliefs about the utility of drinking as a means of reducing
      stress that in the alcohol literature is referred to as "escapist" drinking.
      Escapist drinking is proposed as an intervening mechanism that is associated with
      a higher probability of alcohol-related mental health problems. Using data from
      the 1999-2000 National Survey of Black Workers, we find that, independent of
      socioeconomic attainment, personal reports of discriminatory experiences have
      direct influences on problem drinking. Consistent with our hypotheses, we also
      find that the effects of personal reports of discrimination are at least
      partially mediated by the endorsement of beliefs that drinking provides an
      effective coping mechanism. We conclude that racial impacts on mental health
      outcomes reflect more than the "simple" effects of constrained socioeconomic
      attainment.

PMID- 14582317
TI  - Race, ethnicity, and depression in Canadian society.
AB  - This study examines racial/ethnic differences in mental health using data from
      the 1996-97 National Population Health Survey. Three hypotheses are tested.
      First, a socioeconomic hypothesis tests if differences in family income,
      education, and low income explain racial/ethnic mental health variation. Second,
      a social resources hypothesis tests if differences in social support explain
      racial/ethnic mental health variation. Finally, an interaction hypothesis tests
      if mental health variation stems from specific interactions of race/ethnicity
      with economic and social factors. Although there are socioeconomic, social
      resource, and interaction effects, the analysis shows that they do not fully
      explain racial/ethnic mental health variation. Overall, our results suggest that
      East and Southeast Asian, Chinese, South Asian, and black Canadians have better
      mental health than English Canadians. Jewish Canadians have poorer mental health
      than English Canadians. All other racial/ethnic groupings have similar mental
      health as English Canadians.

PMID- 14582318
TI  - A research agenda for the black middle class: work stress, survival strategies,
      and mental health.
AB  - In this article we discuss the social position of the black middle class and two
      forms of work stress that appear unique to this group: token stress and social
      rejection. We outline a research agenda for studying: (1) the relationship
      between these stressors and mental health in the context of the work environment,
      and (2) the type of strategies that appear especially efficacious (or
      problematic) with regard to these problems. We begin the paper with a contextual
      discussion of the black middle class. We then offer a set of theoretical
      predictions about the relationship between work stress and mental health among
      middle class African Americans. We conclude the article with recommendations for
      future research, and we identify the implications of the research agenda for
      social policy efforts to diversify the workplace.

PMID- 14582319
TI  - [Genetic and epidemiological investigation of a birth cohort of boxers].
AB  - The aim of this project, which ran from 1 January 1994 to 1 January 1999 (and
      which will be continued up to 2004), was to study mortality, disease incidence,
      and risk factors in a birth cohort of purebred boxer dogs born between January
      1994 and February 1995 in the Netherlands (n = 2629). The ancestry of the boxer
      dogs in the cohort was considered a major risk factor. Special attention was
      given to genetic disorders, because a system for genetic counselling was being
      planned; however, non-genetic risk factors were also studied. Participation by
      breeders and owners of boxer dogs was very high. Pup mortality was 22% and was
      mainly caused by individual pup factors. Between 2 months and 4 years of age, 123
      (7.5%) dogs died; the survival rate was 92.5%. The main causes of death were
      epilepsy (n = 23), heart disease (n = 22), and traffic injury (n = 13). Over the
      same age range, on average a boxer dog suffered about 4.25 times from a non
      serious disease, mainly of the gastro-intestinal tract, upper respiratory tract,
      or locomotion system, but 20% had a serious, chronic disease. A relatively high
      heritability estimate (h2) was found for four diseases: cheilo-palatoschisis (h2
      = 0.27), cryptorchism (h2 = 0.24), lesions of cruciate ligaments and menisci (h2
      = 0.28), epilepsy (h2 = 0.36). Selection by means of genetic counselling,
      according to a programme developed on the basis of the results of this study, can
      reduce the frequency of these genetic diseases in purebred populations of boxer
      dogs. This genetic counselling programme will also be effective in other breeds
      of dog because it is based on linking specific pedigree and health information
      with a generally applicable method of estimating breeding values.

PMID- 14582320
TI  - [A deadly vacation-vaccination].

PMID- 14582321
TI  - [Infectious bovine rhinotracheitis outbreak on a mostly BHV-1 free farm can
      result in great damage].
AB  - In a suckler herd with 110 cows (without young stock born in 2003) 5 cows died
      within 10 days, 6 calves were born dead prematurely and 5 calves were born alive
      but prematurely. The diagnosis BHV1-infection was based on clinical symptoms and
      confirmed with PCR. The clinical signs, diagnostic methods, therapy, risk
      analysis and prevention are discussed.

PMID- 14582322
TI  - [Genetic and epidemiological investigation in boxers. Cooperation between
      veterinarians and researchers].

PMID- 14582323
TI  - [Conversation with ISO-auditor. "If you do it right, you do it for yourself and
      not for the auditor." (Interview by Jan Hulsen)].

PMID- 14582324
TI  - [Fluoroquinolone-related blindness in cats].

PMID- 14582325
TI  - [Acquired hepatitis E from eating raw meat].

PMID- 14582327
TI  - [AIDS: status in the world and in Colombia 20 years later].

PMID- 14582326
TI  - [Questions about handling by insurance company NZH].

PMID- 14582328
TI  - [Polymorphism of human HLA-DRB1 leukocyte antigen alleles and its association to
      juvenile rheumatoid arthritis in a sample of Colombian mestizo children].
AB  - Oligotypes of the human leukocyte antigen HLA Class II, DRB1 alleles were
      characterized at the molecular level in a group of Colombian children suffering
      juvenile rheumatoid arthritis (JRA). The distribution of these alleles was
      examined in a group of Colombian mestizo children (genetic admixture of
      Amerindians, Europeans and Africans) suffering from clinically distinct JRA
      subsets in order to detect HLA allele frequency differences in patients with
      different JRA subsets. A group of 65 patients with JRA and 65 controls were
      characterized for the subtypes of the HLA-DRB1 alleles using polymerase chain
      reaction with sequence-specific oligonucleotide probes (PCR-SSOP). The
      oligotyping protocol recommended by the 12th International Histocompatibility
      Workshop held in St. Malo, Paris, in 1996, was used. Subtype HLA-DRB1*1104 was
      the allele most strongly associated with susceptibility to JRA (Fisher's p =
      0.013, odds ratio (OR) = 16.79, etiologic fraction (EF) = 0.93). HLA-DRB1*1602
      was also associated with susceptibility to a lesser degree (Fisher's p = 0.016,
      OR = 8.98, EF = 0.88). HLA-DRB1 alleles participating in JRA protection were HLA
      DRB1*1501 (preventive fraction (PF) = 0.466, p = 0.005) and HLA DRB1*1402 (PF =
      0.49, p = 0.009). The relationship between some HLA-DRB1 alleles and clinical
      features was also compared. The presence of rheumatic factor was associated with
      the alleles HLA-DRB1*0407 (p = 0.05, OR = 11.2, EF = 0.45) and HLA-DRB1*1302 (p =
      0.02, OR = 22.8, EF = 0.63). There was also an association between HLA-DRB1*0701
      (p = 0.001, OR = 58, EF = 0.73) with expressing ANA +. We found that in the
      oligoarticular subset, the allele HLA-DRB1*1104 (p = 0.0034, OR = 41.53, EF =
      0.97) was the one expressed most commonly. In the poliarticular group, the
      alleles most frequently expressed were HLA-DRB1*0404 (Fisher's p = 0.012, OR =
      8.75, EF = 0.88). In patients with systemic JRA, the HLA-DRB1*1602 allele (p =
      0.005, OR = 21.33, EF = 0.95) was most frequent. These results suggested that the
      MHC genes of mestizo children influence not only the clinical expression of the
      disease, but also the susceptibility to its development.

PMID- 14582329
TI  - [Identification of antigens of Colombian Giardia duodenalis isolates recognized
      by total IgG and subclasses].
AB  - Antigen profiles were described for Giardia duodenalis cysts and trophozoites
      that are recognized by IgG and its anti-G. dudodenalis subclasses (IgG1, IgG2,
      IgG3, IgG4). Antigens were identified by Western blot from G. duodenalis cyst and
      trophozoite isolates. Cysts and trophozoites were each subjected to protein
      separation by SDS-PAGE. The proteins were then transferred to nitrocellulose
      membranes by electroimmunoblot, and their antigenicity was determined by exposing
      them to sera from patients with confirmed diagnosis of G. duodenalis infection.
      The antigen-antibody reaction was revealed by specific alkaline phosphatase
      antibody conjugates against IgG, IgG2, IgG3, IgG4: bands were visualized by
      addition of the substrate 5-bromo-4-chloro-3-indolyl-phosphate and the stain
      nitro blue tetrazolium. The bands were read and analyzed by linear regression
      using Quantity One software. Thirty two antigens were simultaneously recognized
      by total IgG anti-G. duodenalis in the cyst and trophozoite stages. The antigens
      varied in molecular weight from 22 to 185 kDa. Nineteen antigens were identified
      by both IgG, and IgG3 anti-G duodenalis, with molecular weights ranging from 42
      to 180 kDa. IgG2 and IgG4 did not identify any antigen in either stage. The
      antigens of molecular weights 27, 30, 31, 33, 45, 49, 57, 78, 89 and 170 kDa are
      shared with G. duodenalis isolates from other geographical regions of Colombia.
      The recognition of cyst and trophozoite antigens of Colombian G. duodenalis
      isolates by IgG, IgG1 and IgG3 anti-G. duodenalis suggested that they are
      involved in the induction of the host immune response.

PMID- 14582330
TI  - [Prevalence of microsporidia and other intestinal parasites in patients with HIV
      infection, Bogota, 2001].
AB  - Opportunistic intestinal parasites are a common cause of diarrhea in HIV-infected
      patients. To determine the prevalence of microsporidia and other opportunistic
      parasites infecting HIV patients in Bogota, Colombia, 115 patients were examined
      for these infections during the year 2001. The institution and the sample percent
      from each are as follows: Santa Clara Hospital, 33.0%; San Pedro Claver, 20.0%;
      Simon Bolivar Hospital, 14.8%; San Jose Hospital, 13.9%; Central de la Policia
      Hospital, 6.1%; Compensar, 5.2%; Colombian League against AIDS, 2.6%; San Ignacio
      Hospital, 2.6%, and the Military Hospital, 1.7%. The average patient age was 36
      years, with a range from 18 to 71 years. Patients with complaint of
      gastrointestinal symptoms were asked to provide two consecutive stool samples.
      The samples were concentrated in formalin-ether and examined microscopically for
      intestinal coccidian parasites by direct wet slide mounts. The prevalence of
      intestinal opportunistic parasites was 10.4% for Cryptosporidium sp. Initially,
      29% of the samples were found to be positive for microsporidian spores using a
      modified Ziehl Neelsen chromotrope stain, but only 3.5% of them were confirmed as
      positive when a calcofluor/Gram chromotrope stain was used. The general
      prevalence of intestinal parasites was 59.1%. The most frequently found pathogens
      were Blastocystis hominis, 25.2%, and Entamoeba histolytica, 13%. In other
      studies with HIV patients in Colombia, lower prevalences of Cryptosporidium sp.
      infection were observed.

PMID- 14582331
TI  - [Risk factors for severe acute lower respiratory tract infection in Bogota,
      2001].
AB  - Severity of acute respiratory infection is higher in developing countries,
      especially among the socioeconomically underprivileged. Viral pneumonias are more
      common, especially among children. A prospective hospital-based case control
      study was undertaken in Bogota between November 2000 and August 2001, aimed to
      identify factors related to severe low acute respiratory infection (SLARI). Cases
      were limited to children aged between 2 months and 5 years who filled WHO
      criteria for SLARI. Controls were children at the same hospital with ARI in a
      similar age range, but without symptoms of chest drawing. A total of 638 children
      (277 cases and 361 controls) were included. The most important risk factors
      included the following: living in borrowed houses (odds ratio (OR) = 2.7; 95%
      Confidence Interval (CI): 1.06-7.07), sharing the bed (OR = 1.88, CI: 1.0-3.7),
      living with more than 9 people (OR = 1.82, CI: 1.0-3.51), and living with smokers
      (OR = 1.4, CI: 1.0-2.05). Of the 114 samples collected (from children at third
      day after beginning of symptoms), 98 had viruses, sincitial respiratory virus was
      the most frequently identified virus (41.8%), followed by influenza A virus
      (3.1%) and influenza B virus (1%). All positive isolates for influenza A and B
      were sent to the United States Center for Disease Control (CDC) in Atlanta, where
      they were classified as influenza A/PANAMA/2007/99-like and influenza
      B/SICHUAN/379/99-like, respectively.

PMID- 14582332
TI  - Clinical and immunological factors associated with lupus nephritis in patients
      from northwestern Colombia.
AB  - A cross-sectional and multicenter study was undertaken to analyze the clinical
      and immunological characteristics at diagnosis associated with nephritis in
      northwestern Colombian patients with systemic lupus erythematosus (SLE). Thirty
      nine patients with lupus nephritis were included and were compared to 100 SLE
      patients without nephritis. A multivariate analysis was performed. The patients
      who developed nephritis had a higher frequency of oral ulcers (41% vs. 21%, OR =
      3.1, 95% CI: 1.3-7.5 p = 0.01) and malar erythema (77% vs. 45%, OR = 4.4, 95% CI:
      1.8-10.8 p = 0.001). Lupus nephritis was observed in 77% of cases during the
      first year of the disease. The frequency of anti-DNA antibodies was higher in
      patients with nephritis, however, differences were not statistically significant
      (83% vs 64%, OR = 2.6, 95% CI: 1.03-6.41, p = 0.06). The presence of other
      autoantibodies (anti-Ro, anti-La, anti-RNP, anti-Sm and anticardiolipin) at
      diagnosis was similar in both groups. This autoantibody profile remained
      unchanged throughout the evolution of the disease. Patients with lupus nephritis
      had a higher prevalence of arterial hypertension (60% vs 10%, OR = 13.7, 95% IC:
      5-37, p = 0.00001) and hyperlipidemia (30% vs 7%, OR = 8.1, 95% IC: 2.5-27, p =
      0.0006) at onset. Finally, patients with lupus nephritis required more
      hospitalizations (> 1) over the course of disease (89% vs 60%, OR = 7.8, 95% CI:
      2.1-29, p = 0.002). In conclusion, lupus nephritis appears early during the
      course of SLE. Malar erythema, oral ulcers, hypertension and hyperlipidemia at
      onset of disease are associated factors. Lupus nephritis is a major risk factor
      leading to repeated hospitalizations. This study may help to assist in public
      health policies in our population in order to improve patient outcomes while
      simultaneously reducing disease costs.

PMID- 14582333
TI  - [Role of the cytokine-3 signaling suppressor protein (SOCS 3) in growth hormone
      resistance induced by malnutrition].
AB  - Nutrition is an important regulator of growth hormone (GH) action. Nutritional
      deprivation causes a GH resistance involving post-receptor alterations in the
      signaling pathway, but the responsible mechanisms remain unknown. Herein,
      suppressors of cytokine signaling proteins (SOCS) were investigated as potential
      agents in GH-resistance induced by malnutrition which inhibits activation of
      Janus kinase 2/signal transductor and activator of transcription 5 (JAK2/STAT5)
      pathway. Growth hormone receptor (GHR), IGF-I and SOCS3 mRNA expression was
      measured in the liver of rats fed with a low protein diet and with GH
      stimulation. Protein diet restriction significantly diminished GHR mRNA and
      receptor binding sites (p < 0.05), but caused a highly increased SOCS3 gene
      expression. In diet-restricted rats, GH administration increased GHR and IGF-I
      mRNA; however, GHR reached basal levels observed in animals feeding with a high
      protein diet. The malnourished group increased SOCS3 gene transcription in
      response to GH administration. These results suggested that a reduced hepatic
      sensitivity to GH was associated with SOCS3 over-expression. In addition,
      ubiquitous distribution of SOCS3 and CIS suggests a role for SOCS proteins as
      tissue specific modulators of cytokine sensitivity.

PMID- 14582335
TI  - [Therapeutic efficacy of 3 treatment protocols for non-complicated Plasmodium
      falciparum malaria, Antioquia, Colombia, 2002].
AB  - High resistance of Plasmodium falciparum malaria to chloroquine poses malaria as
      a major public health problem in Colombia. In this context, the therapeutic
      response of uncomplicated P. falciparum malaria patients to chloroquine (CQ),
      sulfadoxine/pirymethamine (SDXP) and combined therapy (SDXP/CQ) was evaluated
      according to the WHO/PAHO protocols of 1998. The comparisons were based on a
      sample of 160 patients with uncomplicated P. falciparum malaria in Turbo and
      Zaragoza (Antioquia, Colombia). Patients were randomly assigned each of the
      treatment categories. The results were statistically similar in each
      municipality. In Turbo percentage of treatment failure was 87.5%, 22.2% and 22.6%
      for CQ, SDXP and SDXP/CQ, respectively, whereas in Zaragoza, the corresponding
      treatment failure was 77.7%, 26.5% and 12.1%. During follow up, 50% of subjects
      with late treatment failure were asymptomatic in Turbo, while 33.3% were
      asymptomatic in Zaragoza. A high level of treatment failure occurred with CQ
      monotherapy, while SDXP and SDXP/CQ had acceptable levels of failure, i.e., below
      25%. The high percentage of late treatment failure in asymptomatic patients may
      contribute to increased risk of persistent transmission.

PMID- 14582334
TI  - [Identification of cyst and trophozoite antigens from Colombian Giardia
      duodenalis isolates recognized by IgA].
AB  - Little is known about the role of IgA in the immune response against Giardia
      duodenalis infection. The current study identified the antigens of Colombian G.
      duodenalis isolates which stimulate the production of IgA anti-G. dudoenalis.
      Cyst and trophozoite stage proteins were separated by SDS-PAGE and their
      antigenicity was determined by Western blot. Without 2-mercapto ethanol (2-ME),
      the protein profile of the cyst stage showed 24 proteins within a molecular
      weight range of 23-270 kDa; with 2-ME, 35 polypeptides ranging from 22 to 241 kDa
      were distinguished. The trophozoite stage protein profile without 2-ME was formed
      by 16 proteins within the range of 24-270 kDa; with 2-ME, 45 proteins were
      present between 18 and 241 kDa. The identification of 20 and 29 antigens from the
      cyst and trophozoite stage, respectively, suggested that G. duodenalis stimulates
      a specific humoral immune response in the human host. The antigens of 31, 57,
      110, 133, and 170 kDa recognized by anti-G duodenalis IgA in both cysts and
      trophozoites corresponded with G. duodenalis isolates from other geographic
      regions, whereas those of 35, 38, 43, 45, 49, 52, 60, 62, 65, 72, 82, 99, 145,
      155, and 185 kDa seemed specific to Colombian isolates. This indicated that
      antigens of 57, 65, 145, and 170 kDa, recognized by anti-G. duodenalis IgA
      antibodies in cysts (with frequencies between 82% and 96%) and trophozoites (with
      frequencies between 86% and 97%) can be considered identification markers for G.
      duodenalis infections.

PMID- 14582336
TI  - [Phenotype characterization of environmental Cryptococcus neoformans isolates].
AB  - Cryptococcosis is caused by the three varieties of C. neoformans with
      physiological and virulence differences, some of which have been studied to
      determine biological aspects of this microorganism. The phenotypical aspects of
      environmental isolates from varieties grubii and gattii were evaluated to
      establish differences associated with their life cycle and virulence. To this
      end, 28 and 31 strains of C. neoformans serotypes A (var. grubii) and C (var.
      gattii) were studied. The microscopic and macroscopic morphology on Sabouraud
      agar and soils, growth rate at 37 degrees C, production of 22 extracellular
      enzymes, haploid fructification, mating type, killer toxin sensitivity patterns
      and virulence in BALB/c mice were evaluated. No differences were observed between
      the two varieties regarding microscopic and macroscopic morphology or growth at
      37 degrees C (p > 0.05). However, a decrease in the cellular and capsular sizes
      of yeast in soil, as compared to Sabouraud, was observed (p < 0.05).
      Additionally, higher enzimatic activity of proteases, phospholipases,
      phenoloxidase and beta-glucosidase was observed in var. grubii isolates as
      compared to var. gattii (p < 0.05). In both varieties, structures related with
      haploid fruitification were observed and all isolates were mating type alpha.
      Killer toxin sensitivity patterns of the isolates of var. grubii were I and II;
      in contrast, in var. gattii, seven different patterns were found: I, V, IX-XIII.
      In the animal model we found that 12 of 22 (54.5%) isolates of var. grubii caused
      the death of the mice during the observation period, while none of the 14 var.
      gattii isolates caused it. The decrease in capsular and cellular sizes of the
      yeast in soil and the frequency of mating type alpha with structures related to
      haploid fructification suggest an important mechanism of production of infectious
      particles in nature. Additionally, greater enzimatic activity of var. grubii can
      be associated with the virulence in the animal model.

PMID- 14582337
TI  - [New findings on the geographic distribution of the verrucarum group (Diptera:
      Psychodidae) in Colombia].
AB  - The incrimination of sand flies belonging to verrucarum species group in the
      leishmaniasis transmission underscores the need for a detailed information on the
      geographical distribution of these species. The current listing adds 34 new
      records that extend significantly the knowledge of the geographical distribution
      of the verrucarum group in Colombia. The most important new records pertain to
      Lutzomyia spinicrassa in the tropical dry forest of the Atlantic coast, Lutzomyia
      ovallesi in the Orinoco and Amazon River watersheds regions of Colombia, and the
      sympatric occurrence of Lutzomyia spinicrassa and Lutzomyia quasitownsendi in the
      eastern chain of the Andes mountains. Additionally, the municipal and altitudinal
      distributions are compiled for 19 new species recorded for Colombia. The series
      townsendi of the verrucarum group generally restricted to premontane and lower
      montane zones based on distribution data on Lutzomyia longiflocosa, L.
      quasitownsendi, Lutzomyia sauroida, L. spinicrassa, Lutzomyia torvida, Lutzomyia
      townsendi and Lutzomyia youngi. The series verrucarum is distributed from the
      tropical lowland to the montane zones, and includes species with wide
      geographical range (Lutzomyia evansi, Lutzomyia columbiana, L. ovallesi,
      Lutzomyia nuneztovari, Lutzomyia nevesi), and species of highly endemic
      distribution (Lutzomyia andina, Lutzomyia disiuncta, Lutzomyia moralesi,
      Lutzomyia antioquiensis). Members of the series pia (Lutzomyia pia, Lutzomyia
      limafalcaoae) and the series serrana (Lutzomyia serrana) occur from the tropical
      lowlands to the lower montane zones. The altitudinal divergences may be
      intrinsically tied to speciation process, especially as it relates to the
      climatic and geologic events that have affected the flora and fauna of the Andean
      region.

PMID- 14582338
TI  - [Mitochondria in the Plasmodium genera].
AB  - In eukaryotic cells, mitochondria are the ATP-producing and oxygen respiring
      organelles. In malaria cells, mitochondria adapts morphologically and
      physiologically to the metabolic conditions of the host. Therefore, in the
      mosquito, gametocytes have aerobic metabolism and a mitochondria of typical
      appearance, whereas in the vertebrate, sporozoites and merozoites respond to a
      microaerophilic metabolism and the mitochondria have cristae inner membranes and
      a low density matrix. Consequently, its electron transport chain and
      susceptibility to mitochondrial-inhibitors differ substantially. The influence of
      metabolic inhibitors on pyrimidine de novo synthesis has been of particular
      interest in malaria drug development. The current review briefly describes
      adaptations of Plasmodium mitochondria during development, biochemical aspects of
      mitochondrial function and the potential of mitochondria as antimalarial drug
      targets.

PMID- 14582339
TI  - [Drying off cows: a comparative study with two dry cow products].
AB  - From September 1998 to September 1999, at drying off 397 cows on 73 Dutch farms
      were treated, with two antibiotic containing dry cow products (cloxacillin;
      penicillin-neomycin). Farms and cows were selected on an increased bulk milk
      somatic cell count (BMSCC) and individual cow somatic cell count. The objective
      of the trial was to compare the efficacy of both products under field conditions.
      Both products proved to be highly effective against streptococci and penicillin
      sensitive staphylococci. Because of the low incidence of infections caused by
      Escherichia coli and penicillin resistant staphylococci no conclusions could be
      drawn on differences in activity for these two pathogens. No significant
      differences were found between the two products in cure rate of existing
      infections at drying off, incidence of new infections during the dry period,
      incidence of clinical mastitis during the dry period and the course of the
      individual cow cell counts during the trial.

PMID- 14582340
TI  - [Is breeding advice sound?].

PMID- 14582341
TI  - [Cleaning and disinfection: tips for the practice].
AB  - Cleaning (removal of visible dirt) and disinfection (reduction of the number of
      micro-organisms to an acceptable level) are necessary to limit 'carry over' of
      infections agents between patients and people as much as possible. Loose dirt
      should be removed prior to the use of a detergent. Apart from cases of
      contamination of an otherwise clean surface or in case of a highly infectious
      agent, thorough cleaning should always precede disinfection. Several active
      ingredients are approved for disinfection of animal accommodation. From the point
      of view of safety and effectiveness, individual chemicals should never be mixed
      or added to detergents. Queries about the use of chemical agents can be addressed
      to the College voor de Toelating van Bestrijdingsmiddelen or the manufacturer of
      the product.

PMID- 14582342
TI  - [Yearly announcement discontinued from the Veterinary Drug Exemption Order].

PMID- 14582343
TI  - [Preservation time after opening?].

PMID- 14582344
TI  - [Predecessors: veterinarians from earlier times (51). Edmond Isidore Etienne
      Nocard (1850-1903)].

PMID- 14582345
TI  - [The veterinarian check mate? Veterinarians move!].

PMID- 14582346
TI  - [Domestic animals and animal husbandry, the sexual selection 'undone'. About
      biological motivations and ambitions].

PMID- 14582347
TI  - [BVD-free: what is the certificate worth?].

PMID- 14582348
TI  - [What do you mean homeopathy bad practice?].

PMID- 14582349
TI  - [Reaction to organization of Working Group of 'Veterinary Phytotherapists'].

PMID- 14582350
TI  - [Reaction to: 'Is private chicken hobby husbandry a danger to the commercial
      poultry industry?' from Dr. A.C. Voeten].

PMID- 14582351
TI  - [Acetaminophen poisoning].

PMID- 14582352
TI  - [Sports and doping].

PMID- 14582353
TI  - [Recent progress of doping tests in sports].

PMID- 14582354
TI  - [The doping of racehorses].

PMID- 14582355
TI  - [A rapid determination kit for acetaminophen].
AB  - Acetaminophen (APAP: N-Acetyl-p-amino-phenol) is widely used as a nonprescription
      analgesic and antipyretic drug. Although APAP is usually well tolerated when used
      at the recommended dose, overdose has been associated with lethal hepatic
      necrosis. This toxicity has been correlated with elevated serum or plasma APAP
      levels and/or a halftime of elimination from these fluids exceeding four hours.
      Therefore a rapid method for determination of APAP is needed to treat a patient
      with an acute APAP overdose. We developed a simple and rapid method for
      determination of APAP and prepared a test kit. The test kit was based on the
      colorimetric method (indophenol method), but not including stinking reagents. The
      reaction mixture assumed pale blue to dark blue according to APAP concentrations
      and the determination range was 10-200 micrograms/mL with the naked eye. It took
      only 15 minutes for this test. In addition, the test kit could be adapted to APAP
      test in urine. We believe that the new APAP determination kit will be a useful
      tool for emergency diagnosis.

PMID- 14582356
TI  - [2 cases of acute retrobulbar neuritis by thinner inhalation; detected methanol
      of high concentration in gas phase assay].
AB  - We encountered two cases of acute retrobulbar neuritis due to lacquer thinner
      vapor sniffing. Two men, aged 21 and 23, had been addicted to thinner sniffing
      for many years. After they became conscious of their symptoms of slight visual
      disturbance, they continued the sniffing for several days until they lost their
      vision. The diagnoses of acute retrobulbar neuritis were obtained from their
      signs and clinical examinations. They recovered to some extent with injection of
      steroids and vitamin B complex administration, but still had severe impairment of
      visual acuity. Lacquer thinner is a mixture of solvents, and toluene is usually
      the main component of the thinner solution. Therefore, in the addiction to
      thinner sniffing, symptoms and signs of thinner intoxication are considered
      mainly to be the results of toluene inhalation. However, in our analysis of the
      thinner gas with gas chromatography, it was revealed that the main component of
      the gas phase of the thinner was methanol, accounting for as much as 60,000 ppm
      of the gas. We consider that in the thinner vapor sniffing, they are inhalating
      mainly methanol, not toluene.

PMID- 14582357
TI  - [A case of acute cibenzoline intoxication in a hemodialysis patient].
AB  - After taking cibenzoline (200 mg/day, p.o.) for 6 days, a 72-year-old man, who
      had been on hemodialysis for one year, complained of general fatigue, chest
      oppression and muscular weakness. These symptoms got worse after taking another
      tablet of cibenzoline on admission. We strongly suspected cibenzoline
      intoxication and stopped cibenzoline p.o. immediately. On the next early morning,
      he became comatose and QRS interval was markedly prolonged on the
      electrocardiogram. The plasma cibenzoline level was 3,248 ng/ml. After
      endotracheal intubation, the respiration was supported with a ventilator. We also
      started hemodiafiltration and his consciousness became clearer with the QRS
      interval shortening. He was weaned from the respirator 8 hours after
      hemodiafiltration started. Finally the concentration of plasma cibenzoline
      normalized to 210 ng/ml after 4 times hemodialysis. Because cibenzoline is mainly
      excreted by kidney, the plasma cibenzoline level should be followed carefully,
      when it is administered in patients with renal dysfunction.

PMID- 14582358
TI  - [A case of chloropicrin detection by purge and trap gas chromatography/mass
      spectrometry].
AB  - Chloropicrin (CP) is an agricultural chemical used as insecticide or fungicide,
      which occasionally causes accidental poisoning and may used in criminal cases
      including suicide and homicide. Although CP is usually analyzed using gas
      chromatography/electron capture detection technique (GC/ECD), further
      identification by gas chromatography/mass spectrometry (GC/MS) may be required
      from the view point of forensic chemistry and also clinical toxicology. However,
      it is very difficult to detect a trace of CP by routine GC/MS. The present paper
      describes a criminal case, in which GC/MS equipped with curie point purge and
      trap sampler was successfully applied to detect a small amount of CP.

PMID- 14582359
TI  - [Practical analysis of toxic substances useful for clinical toxicology--7-
      Carbamate pesticides].

PMID- 14582360
TI  - [Commentary on the standard therapeutic practice of poisoning recommended by
      Japanese Society for Clinical toxicology--2--Activated charcoal and cathartics].

PMID- 14582361
TI  - [Adult cases of naphazoline-containing antiseptic first aid liquid poisoning].

PMID- 14582362
TI  - [Sudomotor dysfunction in Parkinson's disease].
AB  - Autonomic dysfunction is often associated with the progression of Parkinson's
      disease (PD). The most frequent manifestations of autonomic dysfunction are
      cardiovascular symptoms, bladder and bowel dysfunction, and sudomotor
      dysfunction. However, sudomotor dysfunction in PD remains poorly understood. To
      evaluate sudomotor function in PD, we quantitatively measured sweating during
      untreated conditions in 20 patients with PD (age, 62 +/- 5 years) and in 10 age
      matched control subjects (60 +/- 6 years). An evaporimeter can measure small
      amounts of water (g/m2h) evaporated from the body. This device was used to
      quantify sweating at different sites of the skin (forehead, arm, dorsal part of
      hand, chest wall, femur, and dorsal part of foot). Sweating demonstrated as
      amount of evaporated water (mean +/- SD g/m2h) was less in the patients with PD
      than in the control participants on the dorsal parts of the hand (13.7 +/- 5.2
      vs. 23.9 +/- 5.5, p < 0.001) and foot (16.0 +/- 6.0 vs. 22.1 +/- 8.3, p < 0.05).
      On the dorsal part of the hand, sweating in the patients with PD at Yahr stages I
      and II was less than that in the control-Participants (15.2 +/- 6.3 vs. 23.9 +/-
      5.5, p < 0.05). Sweating in the patients with PD at Yahr stages III and IV was
      less than that in the control participants on the dorsal parts of the hand (10.8
      +/- vs. 2.7 vs. 23.9 +/- 5.5, p < 0.001), and foot (10.9 +/- 2.3 vs. 22.1 +/-
      8.3, p < 0.005). Sweating on the dorsal part of the foot was less in the patients
      with PD at Yahr stages III and IV than that in those at Yahr stages I and II
      (10.9 +/- 2.3 vs. 18.4 +/- 6.1, p < 0.05). Sweating on the forehead in the
      patients with PD at Yahr stages I and II stage was slightly but not significantly
      less than that in the control participants (21.8 +/- 3.8 vs. 32.7 +/- 11.9, p <
      0.2). Sweating on the forehead in the patients with PD at Yahr stages III and IV
      was sightly but not significantly greater than that in those at Yahr stages I and
      II (25.4 +/- 5.6 vs. 21.8 +/- 3.8, p < 0.2). Increased sweating on the forehead
      skin might compensate for decreased sweating on the extremital skin. Our results
      suggest that sudomotor dysfunction in PD primarily affects the distal parts of
      the upper and lower extremities. Sudomotor dysfunction affecting distal parts of
      the extremities worsens with increased severity of PD.

PMID- 14582363
TI  - [The changes of clinical characteristics in 100 Japanese amyotrophic lateral
      sclerosis patients between 1980 and 2000].
AB  - OBJECTIVE: To define changes of clinical features in amyotrophic lateral
      sclerosis (ALS) over the past 20 years and prognostic indicators of ALS from a
      single hospital-based retrospective survey. BACKGROUND: One of the important
      tasks in ALS research is to determine differences between patients who progress
      at different rates. Predicting survival time in ALS helps both physicians and
      patients to make decisions regarding assisted ventilation. PATIENTS/METHODS: A
      total of 100 patients (61 men, 39 women) hospitalized between 1980 and 2000 were
      investigated in the study. Subjects were divided into Groups A and B (Group A: n
      = 50, diagnosed between 1990 and 2000; Group B: n = 50, diagnosed between 1980
      and 1990). Group C comprised 34 patients supported by artificial ventilation
      between 1980 and 2000. Information was obtained for all patients regarding time
      of individual primary end-point (PEP, time of death or required ventilation
      support), secondary end-point (SEP, time of death after artificial ventilation)
      or being alive with or without ventilation support. Combined type of ALS was
      defined as two or more regions presenting simultaneously at initial onset.
      Progression rate was calculated as the time (months) required for a 1-point loss
      on the ALS functional rating scale (ALS-FRS), using 1/delta FS:1/delta FS =
      duration (months) from onset to diagnosis/(48-ALSFRS at diagnosis) RESULTS: Mean
      age at onset has increased in the past 20 years from 59.4 years (group B) to 62.5
      years (group A). An increased incidence has been observed in the patients over 70
      years with ALS (A:n = 8 vs. B:n = 4). The frequency of assisted ventilation
      support had been significantly increased for 22 of 44 group A patients (50%)
      including 5 patients supported by non-invasive positive pressure ventilation,
      compared to 12 of 48 group B patients (25%, P < 0.01). Two patients in group B
      and 6 patients in group A who were still alive at time of the investigation were
      excluded. Mean interval between symptom onset and diagnosis was 14.7 months
      (A:14.0 months; B:15.4 months). No differences were observed between groups A, B
      and C regarding sex ratio, mean total ALS-FRS score at diagnosis. Mean survival
      times were as follows obtained from Kaplan-Meier survival curves; group A:30.8
      months, group B:31.0 months until the time of PEP, group C:67.2 months until the
      time of SEP. Symptoms started in the upper limbs (U) in 37 patients, in the lower
      limbs (L) in 34, in the bulbar region (B) in 19, as combined type in 9 and in
      respiratory muscles in 1. Mean survival time until PEP was 33.9 months for U,
      34.8 months for L, 28.6 months for B and 18.2 months for C (P < 0.001). Combined
      type patients with ALS revealed shorter the time until diagnosis (*P < 0.01) and
      faster the time until PEP than the other ALS types (P < 0.001 Log-rank test). A
      significant correlation was found between 1/delta FS and the time until PEP (y =
      9.64x + 12.6, r2 = 0.545, p < 0.001, y = PEP, x = 1/delta FS). CONCLUSIONS:
      Combined type ALS displayed significantly shorter time to PEP than other types.
      ALS outcome was significantly related to the progression rate of symptoms from
      total score for ALS-FRS at time of diagnosis.

PMID- 14582364
TI  - [A follow-up study on brainstem atrophy in progressive supranuclear palsy--when
      does brain MRI contribute to the differential diagnosis between progressive
      supranuclear palsy and Parkinson disease?].
AB  - OBJECTIVE: To investigate when the MRI can discriminate progressive supranuclear
      palsy (PSP) from Parkinson disease (PD). METHODS: We obtained the following
      parameters using T1-weighted axial images of the midbrain and the middle pons
      from 40 studies of 17 PSP patients and 26 studies of 26 PD patients; 1.
      anteroposterior diameter of the pons (Pons AP), 2. anteroposterior length of the
      pontine tegmentum (Pons T), 3. anteroposterior diameter of the midbrain (Midbrain
      AP), 4. ratio of anteroposterior diameter of the pontine base to that of the
      pontine tegmentum (Pons B/T ratio), 5. ratio of the sum of the bilateral crus
      cerebri widths to the midbrain AP (Midbrain [Cr + Cl]/AP ratio). All the PSP
      patients were studied more than twice and each study was classified into four
      groups according to the duration of the illness; (1) less than 24 months (7
      studies), (2) from 24 to 47 months (10 studies), (3) from 48 to 71 months (14
      studies) and (4) 72 months or longer (9 studies). RESULT: The first MRI studies
      (duration of disease 39.9 +/- 22.1 months) were compared with the second studies
      (duration of disease 67.6 +/- 31.6 months) in 17 PSP patients. Pons AP, Pons T,
      and Midbrain AP were significantly smaller in the second studies, indicating
      progressive pontine and midbrain atrophy. Compared with the PD group, the PSP
      group showed significant atrophy four years after onset of the disease in Pons AP
      and two years in Pons T. Pons B/T ratio, and Midbrain [Cr + Cl]/AP ratio were
      significantly smaller in the PSP group two years after onset, suggesting midbrain
      and pontine tegmentum atrophy. The diagnostic MRI criteria of Pons B/T ratio more
      than four and Midbrain [Cr + Cl]/AP ratio more than two each showed accuracy in
      PSP of more than 70% two years after onset. CONCLUSIONS: Discrimination of PSP
      from PD was difficult during the first two years after onset. The atrophic
      process in the midbrain and the pontine tegmentum may precede that of the pontine
      base. Pons B/T ratio and Midbrain [Cr + Cl]/AP ratio presented here are
      potentially good indexes for the discrimination of these two diseases.

PMID- 14582365
TI  - [An autopsy case of multiple system atrophy with a heteroallelic ceruloplasmin
      gene mutation].
AB  - We reported a 69-year-old woman with multiple system atrophy (MSA), who had a
      heteroallelic missense mutation (G1874A, Gly-->Glu) in the exon 11 of the
      ceruloplasmin (Cp) gene. At the age of 64, she began to complain of progressive
      gait disturbance, which was resistant to anti-Parkinsonian drug treatment.
      Neurological examination revealed parkinsonism such as rigidity, akinesia, mild
      tremor and postural instability, accompanying saccadic eye movement, dysarthria,
      dysphagia, orthostatic hypotension and bladder disturbance. She showed neither
      cerebellar signs nor dementia. Serum Cp and copper concentrations were 13-18
      mg/dl and 38-56 micrograms/dl, respectively, which were decreased to about a half
      of normal values. Brain MRIs revealed high intensity areas in the bilateral
      putamens in the T2-weighted image, and mild pontine base atrophy. She died of
      respiratory failure due to laryngeal paresis after five years from the onset.
      Neuropathological examination revealed brown-colored putamens, where there was
      severe neuronal cell loss with gliosis. Though atrophy of the pontine base was
      mild, transverse myelinated fibers were pale in Kluver-Barrera stain. There were
      Purkinje cell loss of moderate degree and appearance of torpedos in the
      cerebellum. Both silver staining and immunohistochemical staining to alpha
      synuclein showed glial cytoplasmic inclusions, which were found predominantly in
      the putamens. These clinical features and neuropathological findings were
      compatible with multiple system atrophy (MSA). Iron staining of the brain
      revealed iron deposition in the putamens and the substantia nigra, but not in the
      pontine base nor in the cerebellum. Furthermore, we failed to reveal it in both
      the liver and the pancreas as well as the thalamus and the caudate nucleus, which
      were common sites of iron deposition in the previous cases of Cp gene mutation.
      We have already reported three other MSA cases with a- or hypo-ceruloplasminemia
      with similar clinical and pathological features to this case. One of them, in
      which gene analysis was also available, did not have any mutations in its Cp
      gene. Therefore, the gene mutation of this case may not be a direct cause to MSA,
      but the fact that the most cases of MSA with hypoceruloplasminemia showed
      striatonigral degeneration (SND) type implies some relationship between
      hypoceruloplasminemia and SND.

PMID- 14582366
TI  - [Quinacrine administration to a patient with Creutzfeldt-Jakob disease who
      received a cadaveric dura mater graft--an EEG evaluation].
AB  - An old antimalarial drug quinacrine is one of the compounds that can inhibit the
      accumulation of pathogenic prion protein in cultured neuroblastoma cells. Here we
      report the result of a clinical trial of quinacrine administration to a patient
      with Creutzfeldt-Jakob disease (CJD). A 37-year-old woman was admitted to our
      hospital for ataxic gait, hallucination and dementia in August 2001. As a past
      history she had received an operation for cerebellar astrocytoma and had a
      cadaveric dura mater graft at 14 years old. After hospitalization she showed
      signs of anxiety, stimulus-sensitive myoclonus, decorticate rigidity, then
      deteriorated pursuit eye movement and voluntary limb movement. The ethics
      committee of Dokkyo University hospital approved this treatment, and the family
      of the subject was fully informed as to the nature and purpose of the treatment
      and gave their consent. One week after the administration of 300 mg/day of
      quinacrine, voluntary limb movement and pursuit eye movement appeared. There was
      PSD on EEG, but one week after administration of the quinacrine, PSD disappeared,
      and a theta wave was recognized as the basic activity on the EEG. But her
      symptoms deteriorated again after 3 weeks, and PSD appeared. Liver dysfunction
      developed 2 months after administration, and the administration of quinacrine had
      to be stopped. Quinacrine was administrated to a CJD patient who received a
      cadaveric dura mater graft and developed CJD 23 years later. The symptoms of the
      patient were transiently improved with the disappearance of PSD on EEG. Although
      the mechanism of quinacrine for the central nervous system is still unclear, this
      case suggests that quinacrine may be clinically one possible drug for treating
      CJD.

PMID- 14582367
TI  - [A central nervous system lupus showing peculiar findings on cranial magnetic
      resonance imaging (MRI)].
AB  - We report a case of central nervous system (CNS) lupus showing peculiar findings
      on cranial magnetic resonance imaging (MRI) with remarkable improvement after
      corticosteriod therapy. The patient was a 28-year-old woman, admitted to our
      hospital with severe fever, general malaise, and facial edema on June 4, 2001.
      After admission, she was diagnosed with systemic lupus erythematosus (SLE). On
      June 6, she showed diplopia at a distance, and on June 10, she suddenly became
      unconscious and developed general convulsions. Cranial MRI showed asymmetrical,
      multifocal, high signal intensity lesions on T2-weighted image (T2-WI) and low
      signal intensity on T1-weighted image (T1-WI). These lesions were primarily
      present in the subcortical white matter, with some detected in the overlying
      cerebral cortex. Gadolinium (Gd)-DTPA enhanced T1-WI showed marked leptomeningeal
      enhancement overlying the lesions on T1-WI and T2-WI. Apparent diffusion
      coefficient image (ADCI) showed high signal intensity in the surrounding areas of
      the T1-WI and T2-WI lesions, and low signal intensity in the central areas of the
      lesions. Diffusion weighted image (DWI) showed high signal intensity in the
      central areas of the low signal intensity on ADCI. Cerebrospinal fluid (CSF)
      examination revealed albuminocytologic dissociation (cell counts of 2/microliter
      and protein level of 108 mg/dl). CSF IgG index was elevated to 1.152 (normal <
      0.7) and interleukin-6 (IL-6) activity to 27.2 pg/ml (normal < 4.0). On June 10,
      Intravenous administration of high-dose methylprednisolone (1,000 mg/day for 3
      days) was started to treat CNS lesions of SLE. Her CNS manifestations, CSF
      findings, and the lesions on the cranial MRI improved remarkably. This is the
      first case report describing the lesions on both ADCI and DWI in a case of CNS
      lupus. The findings of ADCI and DWI suggest that the lesions of high signal
      intensity on ADCI indicate interstitial edema caused by inflammatory
      microangiopathy, and the lesions of high signal intensity on DWI and low signal
      intensity on ADCI indicate cytotoxic edema caused by ischemic change resembling
      microinfarction. We speculate that in addition to usual T1-WI and T2-WI,
      performing ADCI and DWI is useful for understanding the pathogenesis of CNS lupus
      lesions, and may play a significant role in the prognosis.

PMID- 14582368
TI  - [A case presenting with trochlear nerve palsy and segmental sensory disturbance
      due to circumscribed midbrain and upper pontine hemorrhage].
AB  - We describe a patient presenting with trochlear nerve palsy and segmental sensory
      disturbance due to circumscribed mesencephalic hemorrhage. A 36-year-old man with
      no past illness visited our hospital complaining of sudden onset of diplopia,
      dysesthesia of the left face and upper extremity, and acuphenes of the left ear.
      Neurological examination revealed left trochlear nerve palsy and segmental
      sensory disturbance of the left side almost above T11 level. Pain and temperature
      sensation were disturbed, but vibration, joint position, graphesthesia,
      kinesthesia, and discrimination sensation were spared. Magnetic resonance imaging
      of the head, performed 7 days after onset, revealed acute to subacute phase
      hemorrhage at the right inferior colliculus. No abnormalities were identified on
      cerebral angiography. Symptoms gradually improved with conservative therapy.
      After about ten weeks, diplopia disappeared and area of sensory disturbance was
      reduced (disturbance of pain sensation reduced to about T4 level, temperature
      sensation to about T9). Segmental sensory disturbance usually accompanies spinal
      cord lesion. However, several cases of similar symptoms following cerebrovascular
      disease of the brainstem have been reported. Conversely, some reports have
      indicated that trochlear nerve palsy due to midbrain hemorrhage accompanies
      sensory disturbance contralateral to the lesion. The nature of sensory
      disturbance is thus variable. The present case suggests that segmental sensory
      disturbance might accompany trochlear nerve palsy caused by hemorrhage of the
      inferior colliculus, as intramedullary fibers of the trochlear nerve and
      spinothalamic tract are located nearby and somatotopy of the spinothalamic tract
      is preserved even at the level of the midbrain.

PMID- 14582369
TI  - [Epstein-Barr virus-associated encephalitis presenting as refractory status
      epilepticus that persisted for nearly 2 months with excellent recovery].
AB  - A 37-year-old woman presented with Epstein-Barr virus (EBV)-associated
      encephalitis that developed into refractory status epilepticus ten days after the
      onset of headache and fever, without signs suggestive of infectious
      mononucleosis. An electroencephalogram showed definite epileptogenic changes,
      including diffuse slow wave bursts with paroxysmal generalized bilateral sharp
      waves. The patient required general anesthesia for nearly two months, but had
      completely improved 18 months later. The patient developed Kluver-Bucy syndrome
      four months after the onset: bilateral frontal hypoperfusion was detected with
      SPECT at this time, but also improved after 18 months. MRI showed a 2-3 mm lesion
      of the cerebellar white matter, which was suggestive of a small demyelinaed
      focus. The patient's serum was positive for EBV DNA within two weeks of onset,
      but negative there-after. However, the CSF was positive for EBV DNA for more than
      five months, with a four-fold increase in the titers of IgG antibody for EBV
      viral capside antigen in the CSF. Given the patient's good recovery from her
      critical condition, her severe encephalitis/encephalopathy with persistent status
      epilepticus probably resulted from an EBV-associated immune-response after the
      reactivation of EBV, rather than from a direct infiltration of EBV into the
      brain.

PMID- 14582371
TI  - [Consideration on spreading mechanisms of cranial neuropathy in Ramsay Hunt
      syndrome: possibility of the vascular mechanism].

PMID- 14582370
TI  - [A case of severe parkinsonism induced by failure of ventriculo-peritoneal shunt
      for aqueductal stenosis].
AB  - A 26-year-old man, who had received a ventriculo-peritoneal shunt for obstructive
      hydrocephalus after possible encephalitis, complained of disturbance of upward
      gaze and difficulty in movement seven months after the shunt implantation. One
      month later, neurological examination revealed upward gaze paresis and rigidity
      of all four limbs, but the neuroimaging studies revealed no ventricular
      dilatation. His symptoms deteriorated, and tremor of the extremities appeared. He
      was admitted to our hospital 10 months after the shunt implantation. He developed
      akinetic mutism soon after admission. Cerebrospinal fluid protein was elevated
      (62 mg/dl). At that time, the shunt reservoir was found to be insufficiently
      filled, and neuroimaging showed dilatation of the lateral and third ventricles
      with no dilatation of the fourth ventricle. A neuroendoscopic third
      ventriculostomy with removal of the previous shunt system gradually resolved the
      parkinsonism within two months, and the patient became capable of walking. The
      dilatation of the ventricles improved on neuroimaging. The present report
      suggests that shunt malfunction should be suspected when parkinsonism occurs in
      patients who have undergone a shunt placement, even though hydrocephalus on
      neuroimaging is not observed.

PMID- 14582372
TI  - [Multiple sclerosis in Tokyo Metropolitan Neurological Hospital: from the view
      points of north latitude and Japan's rapid economic growth].

PMID- 14582373
TI  - JCAHO offers two alternative ways to fulfill the periodic performance review.

PMID- 14582374
TI  - Make the most of Jayco.

PMID- 14582375
TI  - Clinical/service groups.

PMID- 14582376
TI  - Sample sizes set for organization assessment of compliance.

PMID- 14582377
TI  - Early changes in MAP2 protein in the rat hippocampus following soman
      intoxication.
AB  - We investigated the time course of both MAP2 (microtubule-associated protein 2)
      levels and its phosphorylation degree in the rat hippocampus during the first 90
      min following the onset of soman-induced seizures. The quantitative immunoblot
      analysis of hippocampal extracts revealed that MAP2 increased significantly in
      response to a sustained epileptic activity (from 60 min of seizure duration). In
      addition, intense MAP2 dephosphorylation was also observed 60 to 90 min after the
      onset of seizures. The possible neuropathological consequences of these two early
      MAP2 changes are discussed in relation to the both excessive stimulation of
      glutamate receptors and subsequent dendritic spine alterations occurring in
      hippocampal neurons soon after soman intoxication.

PMID- 14582378
TI  - Biochemical changes induced in liver and serum of diplodiatoxin (Stenocarpella
      maydis) treated male and female rats.
AB  - Present study was conducted to investigate the acute and sub-acute toxic effect
      of diplodiatoxin with special reference to biochemical membrane bound enzymes
      like aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT) and RBC
      acetylcholinesterase (AChE) in male and female rats. For acute study, rats were
      treated with a single oral dose of 5.7 mg/kg of diplodiatoxin, whereas for sub
      acute study, the rats received 0.27 mg/kg/day for 21 days. Acute and sub-acute
      diplodiatoxin treatment caused loss in body weight and feed intake along with
      symptoms including irritation, dullness, tremors and convulsions. Diplodiatoxin
      caused a significant increase in serum ASAT and ALAT and a decrease in activity
      in the liver in both acute and sub-acute studies. This compound also
      significantly inhibited RBC AChE. Sexual dimorphism was observed when male rats
      were compared with female rats (p < 0.05). The enzyme alterations observed in the
      affected enzymes recovered to the normal levels by day 7 post treatment
      (withdrawal study) in both acute and sub-acute treated rats. A negative
      correlation was observed with regard to these enzymes when serum was compared
      with liver. These enzyme profiles show increases in serum with parallel decrease
      in liver, indicating necrosis of liver. These results suggest that diplodiatoxin
      has potential to affect hepatic end-points.

PMID- 14582379
TI  - Mutagenicity assay in Salmonella for thirteen 2-substituted-1 H-phenanthro (9,10
      d) imidazoles.
AB  - Some 2-substituted-1 H-phenanthro [9,10-d] imidazole compounds synthesized as a
      predrugs were tested in mutagenicity assays in Salmonella strains TA97, TA98, and
      TA100 using a plate incorporation assay both with and without S9 mix. The 10
      substances were mutagenic in TA97 and five of them were mutagenic only with
      metabolic activation, whereas one of them did not require the addition of S9. The
      eight substances were mutagenic in TA98 only with S9. For TA100, seven substances
      showed positive results both with and without S9, however another four required
      S9, whereas only one of them did not required metabolic activation. In summary,
      all of 13 substances derived from phenanthro [9,10-d] imidazole were found to be
      mutagenic for at least one or two of the three strains and their mutagenicity are
      discussed.

PMID- 14582380
TI  - The protective effects of acetylsalicylic acid on free radical production in
      cisplatin induced nephrotoxicity: an experimental rat model.
AB  - Cisplatin-induced nephrotoxicity is closely associated with an increase in lipid
      peroxidation. In several previous reports it was claimed that acetylsalicylic
      acid (ASA) shows its therapeutic potential as a free radical scavenger. The aim
      of the study was to investigate effects of ASA on cisplatin induced
      nephrotoxicity in an experimental rat model. Control animals (n:7) were
      administered 1 mL saline solution intraperitoneal (i.p.). Cisplatin group (n:7)
      was treated with a single dose of cisplatin i.p. (6 mg/kg), ASA group (n:7) was
      treated with i.p. (2.5 mg/kg) per day during the study, cisplatin plus ASA group
      (n:7) was administered single dose cisplatin i.p. (6 mg/kg) plus ASA (2.5 mg/kg)
      during 5 days. At the end of the study, Catalase (CAT), Glutathione Peroxidase
      (GSH-Px), Superoxide Dismutase (SOD), Nitric Oxide Synthase (NOS) enzymes
      activities and Malondialdehyde (MDA), Antioxidant Potential (AOP) levels were
      measured in both erythrocytes and renal tissues. Urea and creatinine levels and
      renal tissue necrosis in cisplatin plus ASA group were significantly lower than
      cisplatin group (p = 0.000, p = 0.014, p = 0.015). SODr activities and MDAr
      levels of cisplatin plus ASA group were also significantly lower than cisplatin
      group (p = 0.000, p = 0.029). These results show that cisplatin and ASA
      combination decreases the levels of urea and creatinine, reduces necrosis and
      improves antioxidant enzyme activities, MDA and AOP in rat kidney.

PMID- 14582381
TI  - Safety evaluation of GX-12. A new DNA vaccine for HIV infection in rodents.
AB  - Toxicity studies for the evaluation of the safety of GX-12, a naked DNA vaccine
      for the treatment of human immunodeficiency virus (HIV) infection, were performed
      in rodents. In a single dose intramuscular or intravenous toxicity study, animals
      were treated with up to 4000 micrograms/kg of GX-12. During the experimental
      period, no abnormalities in mortality, clinical finding, or body weight change
      were observed. For subacute toxicity study, GX-12 was administered
      intramuscularly once a week for thirteen weeks to rats at dosages of 0.250, 1000,
      or 4000 micrograms/kg. Throughout the experimental period, no dead animals,
      notable clinical signs, changes in body weight gain, or food and water
      consumptions were observed. Ophthalmic examination, urinalysis, hematology, and
      serum chemistry, revealed no abnormalities. In addition, there were no changes in
      gross findings, organ weight, and histological findings. Based on these results,
      the NOAEL was estimated to be excess of 4000 micrograms/kg. To assess the
      possible effects on the immune system, we investigated the induction of anti-DNA
      or anti-myosin autoantibodies in mice immunized and boosted with GX-12, and anti
      GX-12 antibodies in rat serum obtained from the subacute toxicity study. GX-12
      neither stimulated the production of anti-DNA or myosin autoantibodies nor
      induced the development of myositis or glomerulonephritis. Therefore, we
      concluded that GX-12 has no toxicity up to 4000 micrograms/kg in this rat model,
      which is 60 times higher than the expected human dose. Furthermore, given the
      limitations of this study, GX-12 neither initiated nor accelerated the
      development of systemic autoimmune responses.

PMID- 14582382
TI  - Lipid peroxidation and urinary excretion of vitamin E in rats submitted to an
      immunological inflammatory process.
AB  - Inflammation is a protective physiologic response, generally controlled by the
      organism at the injury site. Vitamin E is the most important antioxidant in the
      lipid phase present in nature and acts by interrupting the chain reaction
      produced by free radicals. The objective of this study was to evaluate the effect
      of inflammation on vitamin E levels and lipid peroxidation in rats. Forty Wistar
      rats (four groups of 10 rats each) were studied over a period of 15 days. Two
      substances inducing the inflammatory process were parenterally administered, anti
      rat basement membrane serum (ABMG) and Freund's complete adjuvant (FAG). Lipid
      peroxidation levels in hepatic and renal tissue and in plasma and urine were
      analyzed and compared with the control (CG). Vitamin E was determined by HPLC and
      lipid peroxidation by quantification of thiobarbituric acid reactive substances
      (TBARS). ABMG produced more (p < 0.05) TBARS in renal and hepatic tissues (0.7 +/
      0.11 and 1.28 +/- 0.27 nmol/g protein, respectively) compared to CG (0.65 +/-
      0.81 and 0.69 +/- 0.13 nmol/g protein). Analysis of TBARS in urine did not show
      statistically significant differences between the experimental groups and the
      control. Vitamin E levels in the hepatic tissue of ABMG and FAG (40.7 +/- 10.04
      and 44.26 +/- 20.24 micrograms/g tissue) were higher than in CG (22.37 +/- 8.20
      micrograms/g tissue) while in kidney tissue and plasma these values were lower (P
      < 0.05). Renal excretion was increased (P < 0.05) in the group that received anti
      rat basement membrane serum (22.39 +/- 0.11 mmol/mL) compared to CG (0.56 +/-
      0.056 mmol/mL). We conclude that the acute inflammatory process causes important
      alterations in the metabolism of vitamin E and lipid peroxidation leading to a
      significantly increased excretion of this vitamin in the urine.

PMID- 14582383
TI  - Genotoxic activities of drug-nitrite interaction products.
AB  - At first 28 orally administered drugs, considered to be potentially nitrosatable
      on the basis of their chemical structure, have been nitrosated with nitrite under
      simulated stomach conditions. A maximum daily dose of each drug was incubated
      with a nitrite concentration that can be found after a normal meal in the stomach
      at 37 degrees C over 1 h. Reaction was started at pH 6.8-7.0 and stopped at pH
      2.0, so we had the same pH change that occurs in the stomach. Secondly the
      genotoxic activities of drug-nitrite interaction products were tested by the umu
      test with Salmonella typhimurium TA 1535/pSK1002 as tester strain in the presence
      and absence of metabolic activation. By the umu-test, among the nitrosation
      products of drugs examined 22 products showed genotoxicity at different levels.
      Other six products showed negative results by the umu-test.

PMID- 14582385
TI  - [Superinstability (TCT/TCC)n of microsatellite DNA in parthenogenetic lizards
      Darevskia unisexualis (family Lacertidae)].
AB  - Using multilocus DNA fingerprinting, we have examined variability of (TCT)n
      microsatellite and M13 minisatellite DNA repeats in populations, families, and
      tissues of Caucasian parthenogenetic rock lizards Darevskia unisexualis
      (Lacertidae). It has been shown for the first time that population and family DNA
      samples of D. unisexualis (75 samples in total) have individually specific DNA
      fingerprinting patterns of (TCT)n fragments. Analysis of inheritance of (TCT)n
      microsatellites in 46 first-generation progeny in 17 parthenogenetic D.
      unisexualis families revealed their extremely high instability. Mutant TCT
      fingerprint phenotypes were found in virtually each animal of the progeny.
      Moreover, varying fragments in the progeny and their original variants in the
      mothers were shown to simultaneously contain (TCT)n and (TCC)n polypyrimidine
      clusters. At the same time, no variability of (TCT)n fragments has been detected
      in the tissues and organs of mature parthenogenetic lizards and in the analogous
      tissues of the two-week-old progeny of this year. This suggests the absence of
      somatic mosaicism and methylation of the corresponding loci in the samples. Along
      with the hyperinstability of (TCT/TCC)n polypyrimidine clusters, we have shown
      that the population and family DNA fingerprinting patterns of M13 minisatellites
      were invariable and monomorphic in the same DNA samples of D. unisexualis. Our
      results indicate that mutations at loci containing polypyrimidine microsatellites
      significantly contribute to the total genomic variability of parthenogenetic
      lizards D. unisexualis.

PMID- 14582384
TI  - [Fundamental and applied aspects of comparative genomics of vertebrates].
AB  - The Human Genome Project stimulated the development of efficient strategies and
      relevant hardware for complete genome sequencing. The comparative genomic
      approach extends the possibilities of using the sequencing data to identify new
      genes or conserved regulatory regions by means of nucleotide sequence alignment
      of the particular regions of the mouse and human genomes, or to trace the
      evolutionary events resulting in the genome structure of modern mammals. The
      review focuses on the use of new molecular cytogenetic methods along with
      computer-aided analysis of the genomes in vertebrates. Several factors hindering
      data analysis are considered. The currently available information on gene
      evolution rate inferred from comparative genomic data is presented. The origin
      and evolution of the genomes of several species are discussed.

PMID- 14582386
TI  - [Induction of SOS-response of cells exposed to autoregulatory factors of
      microorganisms].
AB  - Among examined microbial growth regulators of alkyl hydroxybenzene group
      (hexylresorcinol, methylresorcinol, and hydroxyethylphenol), only hexylresorcinol
      induces cellular SOS response, demonstrating a dose-dependent increase of the
      induction factor in the SOS chromotest with the Escherichia coli PQ37 strain. At
      the highest of used concentrations (100 micrograms/ml), hydroxyethylphenol and
      nonalkylated resorcinol were shown to exert a weak toxic effect, reducing the
      activity of constitutive alkaline phosphatase, but did not induce SOS response.
      Nontoxic methylresorcinol did not induce genome damage, which can trigger SOS
      functions. It is concluded that substitutions in phenolic ring affect genotoxic
      activity of alkylresorcinols.

PMID- 14582387
TI  - [Structural and functional variability of genetic systems for catabolizing
      polycyclic aromatic hydrocarbons in Pseudomonas putida strains].
AB  - The genetic control of naphthalene, phenanthrene, and anthracene biodegradation
      was studied in three Pseudomonas putida strains isolated from coal tar- and oil
      contaminated soils. These strains isolated from different geographical locations
      contained similar catabolic plasmids controlling the first steps of naphthalene
      conversion to salicylate (the nah1 operon), functionally inoperative salicylate
      hydroxylase genes, and genes of the metha-pathway of catechol degradation (the
      nah2 operon). Salicylate oxidation in these strains is determined by genes
      located in trans-position relative to the nah1 operon: in strains BS202 and
      BS3701, they are located on the chromosome, and in the strain BS3790, on the
      second plasmid.

PMID- 14582388
TI  - [Organization and differential staining of chromosomes from the endomitotic
      nucleus of trophocytes Calliphora erythrocephala (Diptera: Calliphoridae)].
AB  - The structure of primary polytene chromosomes and general architecture of nurse
      cell nuclei was studied in Calliphora erythrocephala using various methods of
      differential chromosome banding(G-, R-, C-banding; Ag- and DAPI staining),
      chromospecific DNA probes and fluorescence in situ hybridization. This analysis
      revealed differential compaction of particular chromosome regions. The
      localization of material of polytene chromosome 6 is retained after its
      rearrangement and the formation of the internal reticular structure of the
      nucleus. Polytene chromosomes of ovarian nurse cells were shown to have blocks of
      dense compact material; some of them were more intensely stained by AgNO3. The
      dynamics of the nucleolus formation was traces at all stages of chromosome
      polytenization in the C. erythrocephala nurse cells.

PMID- 14582389
TI  - [Localization of cohesin complexes of polytene chromosomes of Drosophila
      melanogaster located on interbands].
AB  - The distribution of cohesin complex in polytene chromosomes of Drosophila
      melanogaster was studied. Cohesin is a complicated protein complex which is
      regulated by the DRAD21 subunit. Using immunostaining for DRAD21p, the cohesins
      were shown to be preferentially located in the interband regions. This
      specificity was not characteristic for puffs, where uniform staining was
      observed. The presence of a few brightly fluorescent regions (five to ten per
      chromosome arm) enriched with cohesin complexes was shown. Some of these regions
      had permanent location, and the others, variable location. No antibody binding
      was detected in the chromocenter. Immunostaining of interphase nuclei of
      neuroblasts revealed large cohesin formations. On the polytene chromosomes of D.
      melanogaster, the Drad21 gene was mapped to the chromocentric region (81) of the
      L arm of chromosome 3.

PMID- 14582390
TI  - [Genetic control of mitosis: features of origin of sister chromatid sets in
      anaphase in Drosophila melanogaster mutant line aar(V158)].
AB  - The effect of mutation aarV158 on anaphase separation of chromatids was studied
      on fixed cells of neural ganglia of Drosophila melanogaster larvae. It was shown
      that mutation aarV158 causes three types of defective chromosome segregation
      manifested as (1) monopolar anaphase, (2) separation of chromatids to an
      abnormally short distance in anaphase, and (3) bridging and lagging of some
      chromatids or prolonged asynchronous separation of sister chromatid sets to the
      poles in anaphase. We believe that the former two types of defective segregation
      are caused by disturbed centrosome separation at the beginning of mitosis and the
      third type, by defects in chromatid separation during anaphase. During the two
      year maintenance of the mutation in a heterozygous state, partial correction
      (adaptive modification) of the defects of type 1 and type 2 (but not type 3)
      occurred. The correction of type 1 and type 2 defects during adaptogenesis
      depended on the genotype: in heterozygotes and homozygotes, respectively type 1
      and type 2 were preferentially corrected. The frequency of type 3 defects
      remained constant during the two-year period of maintenance of the mutation in a
      heterozygous state. However, in all variants of the experiment, their frequency
      decreased with increasing distance between the sister chromatid sets. In the
      cells that completed the previous division with abnormalities, the checkpoint
      system is supposed to effectively arrest the cell cycle in the subsequent
      division.

PMID- 14582391
TI  - [Epigenetic variability induced by nicotinic acid in Triticum aestivum L].
AB  - The effect of nicotinic acid (NA) on hereditary traits of spring common wheat
      cultivar Kazakhstanskaya 126 (K.126) were studied under the laboratory and field
      conditions. Treatment of seeds and vegetating plants with 0.01-0.1% NA (aqueous
      solution) induced heritable epigenetic changes in wheat. As a result, strong tall
      plants with the long productive spike, large seeds, and several quantitative and
      qualitative characters other than in the original cultivar were obtained in the
      second and further generations after treatment. Crosses of changed plants with
      each other did not result in segregation with respect to leaf downiness or
      anthocyan stem color in F2-F4, suggesting the same epigenetic state of genes
      responsible for changed characters. In crosses with the original cultivar,
      characters of the changed plants always dominated in F1. Basing on the current
      views, the changes were attributed to a transition of the hl1 and pc recessive
      marker genes into new, dominant epiallelic states Hl1 and Pc, which respectively
      determine downy leaves and the colored stem. The NA effect was specific, since
      only one type of the variation was observed. The changed characters were stable,
      and no reversion to the original phenotype was detected in 57 generations.

PMID- 14582392
TI  - [Heterochromatic regions in corn A- and B- chromosomes].
AB  - A collection of maize forms from the Vavilov All-Russia Institute of Plant
      Breeding (VIR) was studied. We compared variation in the following traits: the
      number and size of heterochromatic knob regions (HKRs) of chromosomes of mother
      pollen cells at pachytene depending on the presence (B+) or absence (B0) of B
      chromosomes; size of B-chromosomes (general, of heterochromatic part); and the
      frequency of B+ plants in groups of forms contrasting in the HKR number (10-15, 4
      10, 2-7, 1-4). It was shown that B chromosomes had statistically significantly
      different effects on HKR polymorphism, relative heterochromatin "content" in the
      cell of multiknob and knobless forms, selection of plants for early ear flowering
      in these forms. The combination of maximum (and minimum) sizes of heterochromatic
      regions of A- and B-chromosomes was established; the genomic level of control of
      the trait is suggested. The role of the relationship of polymorphism at
      heterochromatic regions of A- and B-chromosomes between them and with the systems
      of maize reproduction is considered as a mechanism of maintenance of optimum
      plant heterozygosity via adaptive ontogenetic redistribution of heterochromatin
      among loci, chromosomes, and gametes.

PMID- 14582393
TI  - [Evaluation of the relevance of using RAPD-analysis for revealing the phylogenic
      connections between cultivars of drum wheat (T. durum Desf.)].
AB  - A comparison of similarity indices between 64 durum wheat cultivars calculated
      using pedigree analysis and RAPD method showed a correspondence between these two
      approaches to estimation of genetic diversity. The associations between the
      results of RAPD clustering and coefficients of parentage (chi 2 test) and the
      coefficient of correlation between similarity matrices were statistically
      significant. However, the correlation was rather weak while pedigree analysis and
      RAPD method did not yield completely identical estimates of genetic diversity in
      the set of cultivars studied.

PMID- 14582394
TI  - [Comparison of three inbred lines of mice by overall and genetic
      radiosensitivity].
AB  - The radiosensitivities of three mouse strains (BALB/cLacY, C3H/SnY, and 101/HY)
      have been compared using the following parameters: survival after irradiation at
      a dose of 6-7 Gy, chromosome aberration frequency in bone marrow cells after
      irradiation at a dose of 1.5 Gy, and the change in testis weight and frequency of
      abnormal sperm heads (ASHs) after irradiation at doses from 0.5 to 4 Gy. Strain
      BALB/c is the most radiosensitive with respect to the survival and chromosome
      aberration frequency in the bone marrow but the most resistant with respect to
      the change in testis weight and the frequency of abnormal sperm heads. Strain
      101/HY was the most resistant with respect to survival and chromosome aberration
      frequency in bone marrow after irradiation but the most radiosensitive with
      respect to testis damage.

PMID- 14582395
TI  - [Analysis of the effects of mutant hairless genes in chimeric mice].
AB  - The autosomal recessive gene hairless (hr) is responsible for the complete
      hairlessness in mice homozygous for this gene. Hair shedding that begins at the
      age of 10 days is caused by an abnormal cycle of hair follicle development
      disturbed at the catagen stage. This results in enhanced programmed cell death
      (apoptosis) and ultimately leads to the complete hair follicle destruction and
      shedding of all hairs by the age of three weeks. To study the phenotypic
      expression of the hr gene in a chimeric organism, we have obtained 12 chimeric
      mice hr/hr <--> +/+ by means of aggregation of early embryos hr/hr and +/+. In
      chimeric mice, the hair shedding has begun two days later than in the hr/hr mice.
      By day 23 of postnatal development, hairless areas were present on the coat of
      chimeric mice or the latter were completely hairless depending on the percentage
      of the hr/hr mutant component. In four chimeras with high content of the mutant
      component (68-76%), the hair shedding process was similar to that in the hr/hr
      mice, though it was accomplished two days later. In three chimeras with 48-51% of
      the mutant component, alternating hairless and hair-covered bands were observed.
      These data suggest that the hr gene acts in epidermal cells of a hair follicle,
      because epidermal cell clones in embryonic skin migrate in the lateral-ventral
      direction coherently and without mixing. However, some chimeras displayed a
      pattern which was not so clear-cut: the band borders were illegible and hairs
      partly covered the hairless areas. In some chimeras, the uniform thinning of the
      coat was observed. Analysis of the effects of the hr mutant gene in chimeric mice
      differing in the ratio between mutant (hr/hr) and normal (+/+) components in
      tissues suggests that the hr gene acts in the epidermal cells of the hair
      follicle. The interactions between cells have an essential effect on the mode and
      degree of the hr gene expression, which leads to distortion of the "ectodermal"
      coat pattern in chimeras.

PMID- 14582396
TI  - [Genetic-demographic study of the Gagauz population of Moldava].
AB  - The genetic demographic structure of the Gagauz population of Moldova has been
      described for the first time. Data of interviews and official records have been
      used to analyze the sex and age structure of the population and marriage
      relationships, as well as to estimate the effective sizes of the populations of
      six settlements and selection intensity (according to Crow's formula). The
      demographic data indicate that social transformations have substantially affected
      the genetic demographic parameters of the population. The gene exchange rate per
      generation has been determined (m = 0.0204 in 1972 and m = 0.0309 in 1997). The
      estimated ratio between the components of Crow's index (I(m) < I(f)) in the
      Gagauz population is similar to those for the populations of developed countries
      with traditionally rural lifestyles. The study of marriage relationships of the
      Gagauz population has shown that Gagauzes are intensely mixing with Moldovans,
      Bulgarians, Russians, and Ukrainians.

PMID- 14582397
TI  - [Polymorphism of genes for xenobiotic metabolism in petrochemical workers].
AB  - Genetic polymorphism of xenobiotic metabolizing enzymes responsible for
      individual susceptibility to different environmental factors was examined in a
      cohort of petrochemical workers occupationally exposed to adverse action of
      chemical compounds. Molecular genetic analysis of the 1462V mutation in exon 17
      of the CYP1A gene demonstrated close similarity between the genotype and allele
      frequency distribution patterns in the industrial and control groups. No
      association between the CYP1A polymorphic alleles and genotypes and the duration
      of service and concomitant diseases was observed. The odds ratio of the disease
      development in the workers carrying heterozygous CYP1A1 mutant allele was 2.2.
      Analysis of the STM1 gene polymorphism demonstrated a decrease in the frequency
      of the homozygous deletion carriers in the workers compared to the control group.
      There were no substantial differences between the industrial and control groups
      with respect to the frequencies of rapid and slow acetylator genotypes revealed
      at the analysis of the NAT2 gene polymorphism. However, considering the
      concomitant diseases, in the corresponding industrial subgroup a clear trend
      towards lower frequency of rapid acetylators was demonstrated. In addition, the
      odds ratio of the disease development for the workers with slow acetylator
      phenotype was 1.7.

PMID- 14582398
TI  - [Prevalence and molecular-genetic typing of nonsyndromal neurosensory deafness in
      the Chuvash Republic].
AB  - Summarized genetic epidemiological characteristics of nonsyndromic sensorineural
      deafness in six raions of Chuvash Republic (Cheboksary, Kanash, Morgaushi,
      Tsivil'sk, Mariinski Posad, and Alatyr') are presented. A total of 264,419
      individuals were examined. Forty-five families (60 affected individuals) with
      autosomal recessive (AR) and 8 families (18 affected individuals) with autosomal
      dominant (AD) nonsyndromic sensorineural deafness (NSSD) were identified. The
      load of AD and AR NSSD in the raions examined was estimated. A correlation
      between the distribution of AR NSSD and genetic drift was demonstrated.
      Furthermore, the load of AR NSSD was substantially higher in the regions with
      higher differentiation level. The Spearman's correlation coefficient value was
      0.87. Typing of the 35delG mutation in the gene for connexion 26 was carried out
      in 34 patients from 26 families with AR NSSD. Comparative estimates of the NSSD
      prevalence in a number of Russian populations were performed.

PMID- 14582399
TI  - [Modeling dynamics of gene net, regulating the cell cycle in mammalian cells].
AB  - The study of the molecular mechanisms determining cellular programs of
      proliferation, differentiation, and apoptosis is currently attracting much
      attention. Recent studies have demonstrated that the system of cell-cycle control
      based on the transcriptional regulation of the expression of specific genes is
      responsible for the transition between programs. These groups of functionally
      connected genes from so-called gene networks characterized by numerous feedbacks
      and a complex behavioral dynamics. Computer simulation methods have been applied
      to studying the dynamics of gene networks regulating the cell cycle of
      vertebrates. The data on the regulation of the key genes obtained from the CYCLE
      TRRD database have been used as a basis to construct gene networks of different
      degrees of complexity controlling the G1/S transition, one of the most important
      stages of the cell cycle. The behavior dynamics of the model constructed has been
      analyzed. Two qualitatively different functional modes of the system has been
      obtained. It has also been shown that the transition between these modes depends
      on the duration of the proliferation signal. It has also been demonstrated that
      the additional feedback from factor E2F to genes c-fos and c-jun, which was
      predicted earlier based on the computer analysis of promoters, plays an important
      role in the transition of the cell to the S phase.

PMID- 14582400
TI  - [Effect of indralin on genetic disruption induced by radiation in mice].
AB  - The effect of indralin on frequency of mutations induced by radiation in germ
      cells, reciprocal translocations, and testicle weight of male mice. The level of
      protective effect against genetic damage varied depending on the radiation dose
      and spermatogenesis stage. The values of the defense coefficient ranged from 0.16
      to 0.35.

PMID- 14582401
TI  - [Thermodynamic models of binding ligands to nucleic acids].
AB  - Models of adsorption were considered, which describe the binding of biologically
      active ligands on DNA templates. The binding is described most comprehensively
      and in greatest detail by the distribution function, which determines the
      probability of detecting the preset number of adsorbed ligands on the template.
      In the case of noncooperative binding, this function corresponds to the Gaussian
      distribution and is characterized by two quantities: the mean value of the
      occupation of the template by ligands and the dispersion of occupation. The
      accuracy of the occupation of the template by ligands is inversely proportional
      to dispersion. As the length of the template and the number of reaction sites
      covered by one ligand upon binding increase, the accuracy of the occupation of
      the template by ligands increases. An important characteristic of binding is the
      degree of coverage of the template by ligands. This characteristic represents the
      portion of template reaction sites covered by all ligands adsorbed on the
      template. If polycations are bound to nucleic acid molecules, the coverage of the
      template determines the transition of nucleic acids to a compact state. The
      degree of template coverage for extended ligands depends only slightly on the
      binding constant in a wide range of concentrations of a free ligand in solution.
      Different adsorption models are considered from the unified point of view. The
      classification of cooperative interactions for a wide class of systems is given,
      from situations when several ligands are bound on nucleic acid templates to a
      situation when templates change by the action of ligands and begin to interact
      with each other.

PMID- 14582402
TI  - [Hopping and superexchange mechanisms of charge transport to DNA].
AB  - A theory for charge transport in nucleobase sequences was constructed in which
      the hole migration proceeds via hopping between guanines. Each hop over the
      adenine-thymine (A-T) bridge connecting neighboring guanines occurs by means of
      the superexchange mechanism. The experimental data and theoretical results for
      various types of nucleobase sequences are compared.

PMID- 14582403
TI  - [Distribution functions, describing the binding of extended ligands with DNA
      molecules. Possible use for cases of DNA condensation].
AB  - Due to noncooperative binding of ligands to DNA molecules, DNA molecules are in
      equilibrium with different numbers of adsorbed ligands. This equilibrium for a
      given concentration of the free ligand in the solution is characterized by the
      distribution function, which describes the probability of revealing the DNA
      molecule with a definite number of adsorbed ligands. If polycations act as
      ligands, DNA molecules with the number of ligands sufficient for neutralizing the
      charges on phosphates may undergo a phase transition. One example of this
      transition is the formation of liquid-crystalline dispersions during the binding
      of DNA to chitosan. We analyzed the binding of chitosan to DNA on the assumption
      that this binding is due to equilibrium adsorption. At a definite concentration
      of chitosan in solution, DNA molecules are in equilibrium with different numbers
      of adsorbed molecules of chitosan. If the number of adsorbed ligands exceeds some
      critical value, the DNA molecule covered with chitosan becomes capable of
      interacting with other DNA molecules. As a result of this interaction
      (attraction), liquid-crystalline dispersions can form. Equations describing the
      dependence of the concentration of DNA molecules on the concentration of the
      ligand in solution were derived. It was shown that, at given parameters of the
      model, it is possible to describe experimental data characterizing the formation
      of cholesteric liquid-crystalline dispersions. The analysis of the data makes it
      possible to reconstitute both the size of the binding site occupied by chitosan
      on the DNA and the energy of interaction of chitosan with DNA.

PMID- 14582404
TI  - [On some properties of spectral portraits of nucleotide sequences, computed my a
      matrix Fourier analysis method].
AB  - The quantitative characteristics of a spectral portrait of the nucleotide
      sequence of E. coli oriC were determined by the method of matrix Fourier
      analysis.

PMID- 14582405
TI  - [Interaction of caffeine with basic nucleic acids my a molecular mechanic
      method].
AB  - To understand some aspects of the biological action of caffeine (CAF), the
      interaction energies for various mutual positions of CAF and DNA bases or
      basepairs were calculated. Three types of mutual CAF-base (CAF-basepair)
      arrangements corresponding to the minima of interaction energy were revealed. One
      type of minima correspond to the stacking arrangement of molecules. This type is
      important for interactions of CAF with DNA monomers and single-stranded
      fragments. The other two types of minima correspond to the formation of
      intermolecular hydrogen bonds. Some of these minima may occur during the
      interaction of CAF with the double helix. One of these types corresponds to the
      nearly in-plane position of molecules. The other type of minima correspond to the
      nearly perpendicular arrangement of molecule planes. The minima of the last type
      are supposed to be the most important for the interaction of CAF with the DNA
      duplex, and interaction energies for this type of minima have the most negative
      values.

PMID- 14582406
TI  - [Possible configuration of dimers of Gua-Cyt bases. Computation by molecular
      mechanic models and density functional theory].
AB  - The energies of interactions between guanine and cytosine in various mutual
      positions were calculated by the methods of molecular mechanics with refined atom
      atom potential functions and the quantum mechanics theory of density functional.
      Both methods indicate three types of mutual positions of bases in local energy
      minima. These types correspond to (1) nearly coplanar base positions with
      intermolecular hydrogen bond formation (base pairing); (2) arrangements of two
      bases in nearly parallel planes one above another (base stacking); and (3) nearly
      perpendicular positions of base planes. According to the calculations, the global
      energy minimum corresponds to the Watson-Crick base pair with three hydrogen
      bonds. A specific feature of the pair is a transition from many positions of type
      (2) to positions of type (1) without any energy barrier. This feature is revealed
      by both methods. Another special feature of this pair is a deviation, for most of
      mutual base positions, of the amine group atoms from the ring plane, the
      deviation being more pronounced for Gua. These features are important for
      understanding the conformational behavior of DNA fragments and the RNA structure.

PMID- 14582407
TI  - [Structural features of proteins by intermittent-contact atomic force
      microscopy].
AB  - Optimal conditions of protein scanning by atomic force microscopy were developed.
      Proteins of different molecular masses (950-11.5 kDa) and different three
      dimensional organization were used to investigate the structural features of
      proteins. The most distinct images of proteins were obtained using a tip with the
      free amplitude in the range of 5-15 nm and with the set-point amplitude in the
      regime of repulsion from the sample. The method allowed one to clearly recognize
      the structural details of large molecules such as immunoglobulins IgM and IgG1
      and Ricinus agglutinin. The revealing of the structural properties of proteins
      with molecular masses of 60 kDa and less was limited by the sharpness of probe
      tips used in the present study. It was shown that, by a quantitative analysis of
      the geometric parameters of molecules, it is possible to distinguish IgG1,
      Ricinus agglutinin, and ricin.

PMID- 14582408
TI  - [Kinetics of inactivation of lectin: analysis of a method of tryptophan
      phosphorescence at room temperature].
AB  - The internal dynamics of muscle actin during inactivation induced by guanidine
      hydrochloride (0.5-1.8 M) was studied by the method of room-temperature
      tryptophan phosphorescence (RTTP). It was shown that the essentially unfolded
      actin intermediate, which appears within the first minutes of incubation with
      guanidine hydrochloride, exhibits no RTTP, suggesting a high lability of its
      structure. Subsequent accumulation of associates of inactivated actin is
      accompanied by a significant increase in the intensity and decay time of RTTP,
      which is caused by the rigidity of the structure of inactivated actin. The
      kinetic dependencies of the intensity and lifetime of RTTP of actin during its
      inactivation depended on the concentration of the protein and guanidine
      hydrochloride.

PMID- 14582409
TI  - [Aggregation of C-reactive protein in solutions at acid pH].
AB  - The hydrodynamic properties of the C-reactive protein (CRP) at different pH were
      studied using quasi-elastic light scattering, size-exclusion liquid
      chromatography, and nonreducing gel electrophoresis. It was shown that a CRP
      solution at pH 5.0-7.2 presents a polydisperse system the major component of
      which is the native pentameric CRP. At pH 4.0-4.5, CRP exists in two states
      having different hydrodynamic properties: the native pentameric form with a
      molecular mass of 120 kDa and with the hydrodynamic radius of 4.03 nm and high
      molecular-weight aggregates with a wide range of their molecular weight
      distribution. The interaction of the C-reactive protein with monoclonal
      antibodies to it indicates that conformation-dependent surface epitopes of the
      protein lose the native structure at pH 5.0-5.5. The aggregation of CRP is an
      irreversible process, which begins in a narrow pH range of pH 5.0-4.5 and is not
      accompanied by the dissociation into subunits but is determined by intermolecular
      interactions of its quasi-native pentamers.

PMID- 14582410
TI  - [Effect of methylmercury on primary photosynthesis processes in green microalgae
      Chlamydomonas reinhardtii].
AB  - The sensitivity of green microalgae Chlamydomonas reinhardtii to methylmercury
      chloride (MeHg) and chloride mercury (HgCl2) was evaluated by measuring
      chlorophyll fluorescence parameters by the pulse-amplitude-modulation (PAM)
      fluorometry. It was shown that MeHg at concentrations above 1 microM decreased
      the Fv/Fm ratio, which characterizes the maximal efficiency of energy utilization
      in photosystem II. The degree of inhibition depended on the time of treatment and
      was always higher under illumination conditions (50 microE.m-2.s-1) than under
      dark conditions. A similar regularity was observed for the delta F/Fm' ratio,
      which characterizes the real efficiency of energy storage at the given intensity
      of the photosynthesis-exciting light. Incubation with 5 microM HgCl2 for 5 h did
      not affect both ratios. The decrease in Fm at constant F0 as well as changes in
      the fast fluorescence kinetics after MeHg treatment of algae cells indicated the
      damage on the donor side of photosystem II and the damage of the electron
      transfer from QA to QB. The reduction of photochemical fluorescence quenching
      (qN) under MeHg treatment is also evidence of the increase in the fraction of
      closed reaction centers (QA-). At the same time, increase in the steady-state
      level of P700 photooxidation indicated a disturbance of electron transfer between
      photosystems. The present study demonstrates that methylmercury treatment damaged
      the photosynthetic electron transfer chain at several sites. The inhibitory
      effect of methylmercury is much stronger than the effect of mercury chloride on
      photosynthetic processes.

PMID- 14582411
TI  - [Effect of DNAase on fluorescent properties of pigment-protein complexes,
      contained in photosystem II].
AB  - It was found that chlorophyll fluorescence spectra and spectra of fluorescence
      excitation of pigment-protein complexes of photosystem II are affected by
      treatment with DNase. Pigment-protein complexes were isolated from pea thylakoid
      membranes. Spectra were measured at room temperature. It was shown that the
      treatment with DNase leads to a 30% increase in fluorescence yield at excitation
      in chlorophyll absorption bands in the fraction containing CP47, CP43, and CP29,
      and also in the fraction containing reaction center complexes with minor
      contaminations of light-harvesting complexes. Upon excitation at 260-300 nm and
      in the region of 500 nm, a diminishing of fluorescence yield takes place. These
      results suggest that pigments and/or pigment-protein complexes are bound to
      nucleic acids. This association, by influencing the pigment properties, can
      participate in the photoregulation of biochemical reactions through changes in
      the thermal dissipation of excited chlorophyll molecules.

PMID- 14582412
TI  - [After effect of heat shock on induction of fluorescence and low temperature
      fluorescence spectra of wheat leaves].
AB  - The dynamics of restoration of variable and millisecond delayed fluorescence of
      chlorophyll a, as well as low-temperature fluorescence spectra at 77 K in leaves
      of 11-day-old wheat seedlings subjected to heat shock (41.5 degrees C, 20 min)
      and cultivated for 4 days under white light of different intensity was
      investigated. A comparative analysis of changes in variable, delayed, and low
      temperature fluorescence of chlorophyll a depending on light intensity and the
      proteolitic activity in leaf homogenates during the restoration of the seedlings
      was carried out. It follows from the data that the restoration of fluorescence
      includes several phases and is stimulated by light. A possible mechanism of
      restoration of fluorescence and photochemical activity of photosystem II is
      discussed.

PMID- 14582413
TI  - [Fluorescent probe 4-dimethylaminochalcone: mechanism of fluorescence quenching
      in nonpolar media].
AB  - The reasons for the high sensitivity of the fluorescent probe 4
      dimethylaminochalcone (DMC) to nonpolar environment were explored. It was shown
      that, at room temperature, the fluorescence quantum yield in nonpolar media at 20
      degrees C is lower than 0.01 (0.001 in methylcyclohexane). However, as
      temperature was lowered to -196 degrees C, the yield in methylcyclohexane
      increased more than 200 times. At the same time, the oscillator strength of
      absorption transition increased, and the absorption spectrum was shifted to red.
      These results, together with quantum chemistry calculations suggest that, for
      fluorescence quenching to occur, some barrier in the DMC molecule, probably the
      barrier of rotation about C-C bonds, should be overcome. In other words, the
      quenching is associated with the transition of DMC molecules from a flat
      conformation (energy minimum) to other, nonflat conformations through rotations
      about C-C bonds. The phosphorescence of DMC at low temperatures was detected.
      This suggests that fluorescence quenching is caused by radiationless transitions
      from the excited singlet level to the ground and triplet levels, and rotation
      about bonds facilitates these transitions.

PMID- 14582415
TI  - [Mathematical modeling of movement of cilia in olfactory cells].
AB  - A mathematical model of the movement of olfactory cilia in different conditions
      was constructed. The realization of the model includes the development of a
      mechanical mathematical rheological model of the behavior of a continuous
      deformable medium, the development of the method of solution adapted to this
      problem, and obtaining a numerical solution, which takes into account different
      starting data. The mathematical modeling of the dynamic behavior of a deformable
      medium was performed using a system of equations for the dynamics of the
      deformable medium and the solution of the corresponding nonstationary system of
      equations in partial derivatives.

PMID- 14582414
TI  - [Effect of osmolar concentration of culture media on exocytosis in isolated
      presynaptic nerve endings of rat brain ].
AB  - The effect of hypotonic and hypertonic shock on exocytosis in rat brain
      synaptosomes was studied using the fluorescent dye acridine orange. It was shown
      that an increase in medium osmolarity leads to calcium-independent exocytosis.
      The response of the probe was directly proportional to the amount of osmolithes
      added. A decrease in medium osmolarity to 230 mOsm led to an increase of acridine
      orange fluorescence, which is comparable with exocytosis occurring by the action
      of 15 mM KCl. This effect was independent of calcium concentration. It is assumed
      that, under hypotonic shock, part of neurotransmitters are released from the
      vesicular pool.

PMID- 14582416
TI  - [Effect of the rate of phytoplankton growth on the spaced-time dynamics of
      plankton communities in an homogeneous environment].
AB  - We use a conceptual mathematical reaction-diffusion model to investigate the
      mechanisms of spatial structure formation and complex temporal dynamics of
      plankton in a heterogeneous environment. We take into account basic trophic
      interactions, namely, "prey-predator" interactions between phytoplankton,
      zooplankton, and fish in upper layers of natural waters. We consider plankton as
      a passive contaminant in turbulent waters. We show that plankton structure
      formation can result from the difference in phytoplankton growth rate in
      neighboring habitats. Phytoplankton and zooplankton biomass is shown to undergo
      both regular and chaotic oscillations. The fish predation rate substantially
      affects the spatial and temporal dynamics of plankton in a heterogeneous
      environment.

PMID- 14582417
TI  - [Role of atrial myosin light chains in modulating the functional properties of
      myocardium].
AB  - To elucidate the functional importance of the appearance of atrial myosin light
      chains (ALC) in ventricles in some cardiomyopathies, a partial (75%) substitution
      of myosin light chains 1 and 2 of the left ventricle for ALC-1 and ALC-2 was
      carried out in vitro. It is shown that this substitution does not lead to changes
      in shapes and sizes of the filaments formed by hybrid myosin but causes changes
      in the shape of myosin heads. The replacement of the light chains increases the
      actin-activated ATPase activity of hybrid myosin by 63%. The results obtained are
      evidence that the substitution of ventricle myosin light chains with atrial ones
      is of physiological importance for the improvement of myosin functional
      properties and thereby for the compensation of the insufficiency of myocardium in
      dilated cardiomyopathy. These data and the data on dynamics of ALC-1 in diseased
      ventricles are important for creating the prognostic test of dilated
      cardiomyopathy development based on the registration of changes in the isoform
      composition of cardiac myosin light chains.

PMID- 14582419
TI  - [Treatment of surface burns with proteolytic enzymes: mathematic description of
      lysis kinetics].
AB  - The lysis of necrotic tissue by a proteolytic enzyme applied to the surface of a
      burn wound was studied. A mathematical model was proposed, which describes
      changes in the thickness of necrotic tissue as a function of the proteolytic
      activity of the enzyme. The model takes into account the inward-directed
      diffusion of the enzyme, the counterflow of interstitial fluid (exudates)
      containing specific inhibitors, and the extracellular matrix proteolysis. It was
      shown in terms of the quasi-stationary approach that the thickness of the
      necrotic tissue layer decreases exponentially with time; i.e., the lysis slows
      down as the thickness of the necrotic tissue layer decreases. The dependence of
      the characteristic time of this decrease on enzyme concentration was obtained. It
      was shown that, at high enzyme concentrations (more than 5 mg/ml), the entire
      time of lysis (after the establishment of quasi-stationary equilibrium) is
      inversely proportional to the concentration of the enzyme.

PMID- 14582418
TI  - [Contractile characteristics of single skinned rat soleus muscle fibers under
      gravitational load: effects of a calcium-binding agent].
AB  - Excessive intracellular calcium accumulation is believed to trigger the
      development of functional and structural changes in muscle fibers under
      microgravity conditions. The hypothesis was testified in the 14-day hindlimb
      suspension study with the application of a Ca(2+)-binding agent (10% EGTA).
      Twenty one rats were divided into 3 groups: cage controls (7), hindlimb-suspended
      rats that received intraperitoneal injections of saline (7), and hindlimb
      suspended rats with EGTA treatment. Whereas the diameter of muscle fibers of
      unloaded rat soleus muscle was 20% less than in the control group (and there were
      no significant differences between rats with injections of EGTA and without
      them), the decrease of maximal tension was more pronounced (more than 50%). This
      discrepancy resulted in a decrease of maximal specific tension. The value of
      absolute tension in rats treated with placebo was by 52%, and in EGTA-treated
      rats by 41% less than in the control group. Thus, there were no significant
      differences in specific tension between this group and the control group.
      Obviously, the injections of EGTA prevented the effects of those mechanisms that
      induce a decline of tension in muscle fibers but are not linked with the
      reduction of fiber size. The Ca/tension curve in hindlimb-suspended saline
      treated rats shifted to the right so that the pCa thresholds changed from 6.85 +/
      0.03 in cage controls to 6.70 +/- 0.04 (p < 0.05), which indicates that
      myofibrils of unloaded soleus are less sensitive to Ca2+. At the same time, the
      pCa threshold in EGTA-treated hindlimb-suspended rats was 6.93 +/- 0.02. It is
      concluded that chronic binding of excess calcium results in an increase in Ca
      sensitivity indices.

PMID- 14582420
TI  - [Decrease in the intensity of the cellular immune response and nonspecific
      inflammation upon exposure to extremely high frequency electromagnetic
      radiation].
AB  - The effect of low-intensity extremely high-frequency electromagnetic radiation
      (EHF EMR, 42.0 GHz, 0.1 mW/cm2, 20 min daily) on cell-mediated immunity and
      nonspecific inflammatory response in mice was studied. The intensity of cell
      mediated immune response in the reaction of delayed-type hypersensitivity and
      nonspecific inflammation was estimated by a relative increase in the thickness of
      foot pad after immunization of animals by sheep red blood cells or zymosan. It
      was shown for the first time that the radiation reduces both immune and
      nonspecific inflammatory responses. It was shown with the use of models of acute
      inflammation and full-thickness skin wounds that EHF EMR suppresses the
      nonspecific inflammatory response but does not influence the duration of the
      pathological process. We suppose that the basis of the effects revealed is the
      modification of functional activity of phagocytic cells under the influence of
      EHF EMR. The results suggest that some therapeutic effects of EHF EMR can be
      realized via the inhibition of inflammatory processes.

PMID- 14582421
TI  - [Computer volume reconstruction of the anatomical structure of the brain].
AB  - The possibility of constructing three-dimensional computer models of the brain
      and intrabrain structures on the basis of stereotaxic atlases for calculating the
      geometry of structures and modeling stereotaxic operations was considered. A
      special program (Contour-1) was developed on the basis of the Kristiansen
      Zedenberg's and Ganapatchi-Denechi algorithms with the use of the OpenGL library.
      Some problems were revealed, which do not allow one to construct three
      dimensional models of the geometry of intrabrain structures (breaks between the
      sections of the brain, insufficient accuracy of the alignment of the images of
      sections relative one another, etc.).

PMID- 14582423
TI  - [Long-range interactions between macromolecules, introduced into smectic liquid
      crystals].
AB  - Equations for the potentials of interactions between macromolecules of different
      shapes incorporated into smectic liquid crystals are presented. In addition to
      accurate equations, simple formula for estimation are given.

PMID- 14582422
TI  - [Microspectral studies of neuroendocrine regulation of gametogenesis in
      mollusks].
AB  - An associated culture of nervous ganglia and gonads was used to study the
      gametogenesis neuroendocrine regulation in mollusks (Mytilus edulis L.). The
      state of oocytes was controlled by microspectral fluorescent analysis on slides
      stained with acridine orange. The object of investigations was Mytilus edulis L.
      collected in La Manch in April-May. A microspectrofluorimetrical investigation of
      samples was carried out in Pushchino. As a criterion of cell synthetic activity,
      the parameter alpha was used. Parameter alpha is the ratio of fluorescence
      intensities in the red (I640) and green (I530) regions of the visible spectrum:
      alpha = I640/I530. The results obtained showed that the nervous system realized
      the endocrine regulation of gametogenesis in mollusks. There was no normal
      development of oocytes in an isolated mantle culture. The development of oocytes
      in a tissue culture proceeds in a similar manner as in the gonads of the native
      organism in normal natural conditions only if the mantle tissue is associated
      either with all nervous ganglia or with the cerebral ganglion alone. It was found
      that the cerebral ganglion plays a key role in the neuroendocrine regulation of
      gametogenesis.

PMID- 14582424
TI  - [Spectral studies of a single cell of marine microplankton. History and
      perspectives].
AB  - Methods and instruments for the spectral analysis of single cells of sea
      microplankton under the conditions of expeditions to the Mediterranean Sea and
      tropical zone of the Atlantic Ocean were proposed. Special emphasis was given to
      the ways of adaptation of sea microplankton communities to unfavorable
      environment with the formation of autotrophic and heterotrophic symbiont
      organisms (Radiolarian, Foraminifera, etc.) having closed cycles of phosphate
      metabolism and variotrophic microorganisms (Cyanophyceae and Dinoflagellata
      class).

PMID- 14582425
TI  - [Successes in medical biophysics (on the 40th anniversary of the Medico
      biological faculty of the Russian State Medical University)].
AB  - On the occasion of the 40-year anniversary of the Medicobiological Faculty of the
      Russian State Medical University, the research activity of the biophysics
      department was summed up. The main result is the creation of medical biophysics
      as part of the medicobiological science. Scientific investigations of the
      biophysics department are reviewed. They are presented as follows:
      chemiluminescence of biological systems; effect of visible light on human and
      animal molecules and cells; application of luminescence methods in laboratory and
      clinical investigations; free radicals and their role in cell biology and
      pathology; medical aspects of molecular biophysics; and biological membranes and
      cell pathology.

PMID- 14582426
TI  - [Cardiology: today and tomorrow].

PMID- 14582427
TI  - [Echocardiography: how it began (the 30th anniversary of the first
      echocardiography made in our country)].

PMID- 14582428
TI  - [Problems of theoretical hematology].

PMID- 14582429
TI  - [Succession in the work of therapists in outpatient and inpatient care].

PMID- 14582430
TI  - [Hypertensive disease--main cause of cardiovascular morbidity and mortality in
      the country].

PMID- 14582431
TI  - [The forward development of emergency care cardiology at the N.V. Sklifosovsky
      Research Institute of Emergency Care (the 80th anniversary of N.V. Sklifosovsky
      Research Institute of Emergency Care)].

PMID- 14582432
TI  - [Natriuretic peptides. Evolution of knowledge].

PMID- 14582433
TI  - [General clinical aspects of the "difficult diagnosis" problem].

PMID- 14582434
TI  - [The 80th anniversary of the journal "Terapevtichesky Arkhiv". Editors-in-chief
      of the journal].

PMID- 14582436
TI  - [Medico-ecological aspects of stable development of Russia].

PMID- 14582435
TI  - [Incidence of celiac disease in patients with chronic diarrhea].
AB  - AIM: To study prevalence of celiac disease (CD) among patients with chronic
      diarrhea (ChD). MATERIAL AND METHODS: Serum levels of IgA-antibodies to gliadin,
      endomysium, reticulin and tissue transglutaminase were examined in 206 patients
      with CD. Biopsies were obtained from a distal portion of the duodenum or a
      proximal portion of the jejunum. RESULTS: CD was diagnosed in 35 (16.9%) of 206
      patients with ChD. The disease was typical in 5 (2.4%) patients and was latent in
      30 (14.5%) patients. Antibodies to gliadin, endomysium, reticulin and tissues
      transglutaminase in diagnostically significant titers were detected in the serum
      of all the examinees with CD. Formation of the antitissue antibodies occurred
      because of destructive-dystrophic alterations of the connective tissue of the
      lamina propria mucosae pointing to the autoimmune nature of a pathological
      process in celiac disease. CONCLUSION: To diagnose CD in ChD patients, it is
      necessary to supplement standard examination with duodenobiopsy, tests for
      antibodies to gliadin, tissue transglutaminase and to tissue structures-
      endomysium and reticulin.

PMID- 14582437
TI  - [Pneumonia: historical and modern aspects].

PMID- 14582438
TI  - [Bronchiolitis: classification, clinical picture, and anatomical pathology].

PMID- 14582439
TI  - [Effect of beta-blockers metoprolol CR/XL and carvedilol on left ventricular
      contractility in patients with chronic low cardiac output].
AB  - AIM: To compare effects of metoprolol CR/XL and carvedilol on global and regional
      contractility of the left ventricle in patients with chronic cardiac failure
      (CCF). MATERIAL AND METHODS: The results of two trials were compared: the effects
      of metoprolol CR/XL and on carvedilol left ventricular contractility in patients
      with chronic cardiac failure (CCF). A total of 52 patients with ischemic heart
      disease (IHD) and dilated cardiomyopathy (DCMP) entered the studies. Of them, the
      treatment was completed in 19 and 20 patients, respectively. Ejection fraction
      (EF), left ventricular end systolic and diastolic volumes were measured at
      radionuclide ventriculography before and 6 months after the start of the
      treatment. RESULTS: Both beta-blockers significantly increased EF and reduced the
      volumes. In both groups the rise of contractility in EF < 30% was similar. EF
      augmentation in patients with DCMP was greater than that in patients with IHD and
      depended on improvement of segmental contractility. CONCLUSION: Significant
      differences were not found in the action of two beta-blockers on global and
      regional contractility of the left ventricle in patients with CCF.

PMID- 14582440
TI  - [Effect of trimetazidine and perindopril on myocardial function and metabolism in
      patients with low cardiac output during postinfarction period].
AB  - AIM: To investigate effects of trimetazidine and perindopril on myocardial
      function and metabolism in patients with cardiac failure after myocardial
      infarction. MATERIAL AND METHODS: A comparative study was mode of the effects of
      6-month therapy with perindopril, trimetazidine alone and in combination on
      clinical symptoms, left ventricular function and perfusion, glucose utilization,
      excretion and utilization of fatty acids in the zones of postinfarction scar,
      periinfarction ischemia and in without infarction changes. RESULTS: Combined
      treatment with the ACE inhibitor and trimetazidine produced positive clinical and
      functional-metabolic shifts in postmyocardial infarction patients with cardiac
      failure. CONCLUSION: The addition to the program of mild cardiac failure
      treatment early after myocardial infarction of an ACE inhibitor and a
      cytoprotective drug (trimetazidine) promotes more complete clinical compensation
      of the patients.

PMID- 14582441
TI  - [Long-term effects of structum administration (according to data from multicenter
      trial)].
AB  - AIM: To evaluate duration of a clinical response to the drug structum in patients
      with osteoarthrosis (OA) of the knee and hip joints as well as structum effects
      on OA course and that of concomitant diseases. MATERIAL AND METHODS: The duration
      of a clinical response to structum after the end of the treatment and its effect
      on OA and concominant diseases course were studied for 12 months in 9 centers
      participating in the study of the drug efficacy and tolerance in patients with
      gon- and coxarthrosis in an open multicenter randomized controlled 6-month trial.
      Out of 555 patients with OA of the knee and hip joints enrolled in the first
      study, the examination covered 373 patients: 159 patients of the test group
      treated for 6 months with structum and 214 controls. By basic clinical parameters
      the groups were similar. Clinical examination was made after structum treatment
      and 12 months later and included assessment of the number of exacerbations,
      hospitalizations, outpatient consultations, days of temporary disability for OA,
      pain in the joints while walking and at rest by the visual scale, Leken's
      functional index, x-ray pictures of the joints, administration of nonsteroidal
      anti-inflammatory drugs (NSAID), exacerbations of concomitant diseases
      (gastrointestinal diseases, arterial hypertension, ischemic heart disease).
      RESULTS: An overall functional Leken's index in patients with gon- and
      coxarthrosis given structum 12 months after the treatment did not reach the
      initial values as well as pain and daily need in NSAID. Structum effect in
      patients with knee joint OA persisted for 4.6 months, in hip joint OA--4.1
      months; in patients with stage I-II the effect lasted longer than in stage III
      (5.2 and 4.6 months vs 4.17 and 3.24 months, respectively. Even short-term
      therapy with structum reduced the number of further exacerbations,
      hospitalizations and visits to their doctor. 12 months after structum therapy the
      effect persisted in 40% patients. Frequency of exacerbations of the concomitant
      diseases was less than in patients on continuous NSAID. CONCLUSION: Structum is a
      highly effective drug against OA as it acts long, reduces frequency of
      exacerbations, hospitalizations, visits to the doctor, duration of disability,
      NSAID requirement and improves the course of some concomitant diseases.

PMID- 14582442
TI  - [Therapeutic efficiency of a combined use of low-intensity laser radiation and
      actovegin in gastroduodenal ulcers with inhibited cicatrix formation].
AB  - AIM: To validate use of intravenous laser blood irradiation (ILBI) combined with
      actovegin administration in indolent gastroduodenal ulcers. MATERIAL AND METHODS:
      Modern endoscopic, morphological, device, biochemical techniques and
      radioimmunoassay were used in examination of 92 patients with indolent
      gastroduodenal ulcers aged 24 to 69 years. ILBI plus actovegin was given in
      failure of standard medicinal therapy. RESULTS: ILBI plus actovegin combination
      produced marked analgetic, anti-inflammatory and detoxication effects. Favourable
      trends were observed in the composition of gastric mucus, detoxication,
      reparative and metabolic processes in the gastroduodenal mucosa, neurohumoral
      regulation. CONCLUSION: Combination of ILBI with actovegin proved highly
      effective in indolent gastroduodenal ulcers.

PMID- 14582443
TI  - [Recent trend in interventional cardiology--drug-containing stents].

PMID- 14582444
TI  - Using provincial client registries for selection of control subjects: lessons
      learned.

PMID- 14582445
TI  - Poliomyelitis vaccination for international travellers.

PMID- 14582446
TI  - Is there a 'treatment gap' in acute coronary syndromes?

PMID- 14582447
TI  - Renal therapeutics: patent highlights January to June 2003.
AB  - Drug-related patents with relevance to renal therapy that were published during
      the first half of 2003 were identified by searching Current Drugs' Patent fast
      alert, evaluated for their relevance, and the most potentially significant of
      these documents are discussed in this review. Of the 19 documents that are
      analyzed in depth in this review, two related to renal cell carcinoma, three each
      to diabetic nephropathy, renal failure and/or allograft preservation or fibrosis,
      and four to inhibitors of angiotensin-converting enzyme or dipeptidylpeptidase
      IV, while only two identified potentially novel drug targets for renal therapy.
      The low number of patents with direct and substantial relevance for renal
      therapies indicates that kidney diseases are receiving relatively little
      attention from drug developers, in spite of their substantial impact on public
      health.

PMID- 14582448
TI  - LXR agonists for the treatment of atherosclerosis.
AB  - Liver X receptor (LXR) alpha/beta nuclear receptors are intracellular sterol
      sensors that regulate expression of genes controlling cholesterol absorption,
      excretion, catabolism and cellular efflux in target organs, including small
      intestine, liver and macrophages. Through co-ordination of the expression of
      target genes in multiple tissues, LXR agonists increase the flux of cholesterol
      from the periphery to the liver, where it is metabolized and excreted into the
      bile. Synthetic dual LXR alpha/beta agonists decrease atherosclerosis in mice,
      however, upregulation of lipogenic target genes and triglyceride elevation in
      rodents reveals a narrow therapeutic window. LXR subtype-selective agonists or
      LXR modulators may dissociate the anti-atherosclerotic and lipogenic effects of
      current dual LXR agonists.

PMID- 14582449
TI  - p38 mitogen-activated protein kinase inhibitors for the treatment of chronic
      cardiovascular disease.
AB  - p38 Mitogen-activated protein kinase (MAPK) has been implicated in cardiovascular
      disease and is activated by various factors, including neurohormones (e.g.,
      catecholamines, angiotensin II and endothelin), hypoxia and wall stress.
      Activation of p38 MAPK can cause cardiac hypertrophy, negative inotropy and
      endothelial dysfunction. All of these conditions lead to chronic cardiovascular
      disease, which is becoming an ever growing burden on society. p38 MAPK inhibition
      may therefore be an interesting therapeutic approach to the treatment of various
      cardiovascular diseases. However, in vitro and in vivo results are conflicting
      and caution must be applied in the translation of bench results to the clinic.

PMID- 14582450
TI  - Rho kinase inhibitors as potential therapeutic agents for cardiovascular
      diseases.
AB  - RhoA and Rho-kinase (ROCK) participate in diverse cellular signaling functions
      such as smooth muscle contraction, cytoskeleton rearrangement, and cell migration
      and proliferation. In smooth muscle, ROCK plays an important role in calcium
      sensitization, an event that controls vascular vessel tone. Recent studies using
      ROCK inhibitors along with cellular and molecular biology techniques have
      revealed a pivotal role of this enzyme in many other aspects of cardiovascular
      function. This review will focus on the current understanding of Rho/ROCK
      signaling pathways and discuss the use of ROCK inhibitors as therapeutic agents
      for cardiovascular diseases ranging from hypertension to atherosclerosis.

PMID- 14582451
TI  - Utility of endothelin-converting enzyme inhibitors for the treatment of
      cardiovascular diseases.
AB  - Endothelins (ETs) are a family of potent peptidic vasoconstrictors that have been
      implicated in the pathogenesis of many cardiovascular disorders such as
      hypertension, myocardial infarction, congestive heart failure, atherosclerosis
      and restenosis. Suppression of the production of these peptides by inhibitors of
      endothelin-converting enzyme-1 (ECE-1), which is involved in the final step of
      post-translational processing of ETs, may therefore have beneficial effects for
      the treatment of these disorders. A number of non-selective and selective ECE-1
      inhibitors have been identified, and this article reviews the pharmacological
      effects of these agents in animal models of cardiovascular diseases and presents
      available clinical data.

PMID- 14582452
TI  - Prospects for prevention and treatment of vascular cognitive impairment.
AB  - With the aging population and rising prevalence of vascular disease in developed
      and developing countries, increasing numbers of individuals are at risk of
      cognitive impairment. Despite the potential of the therapeutics that are
      currently under investigation, none have yet fulfilled their promise for the
      prevention and treatment of dementia. The term vascular cognitive impairment
      (VCI) describes individuals with significant cognitive impairment arising from
      vascular disease. Risk factors predisposing to stroke correlate with brain
      changes, cognitive loss and Alzheimer's disease pathology. The volume of the
      infarcts and white matter changes, silent lacunar infarcts, and global and
      regional brain atrophy may be imaged non-invasively, targeted as surrogates of
      the dementia processes and considered parameters to be targeted for
      interventional strategies. As the greatest chance to prevent cognitive impairment
      and its progression is by intervening in the early stages or prior to any change,
      the development of preventative therapeutics is an important strategy. Non
      invasive magnetic resonance imaging techniques may help to identify a subgroup of
      patients in whom infarct prevention, via risk factor control, may be of paramount
      importance. As the pathophysiology of dementia becomes more fully understood by
      coupling neuropsychological with neuroimaging, genetic and pathological features,
      there is the potential for the establishment of diagnostic criteria of the early
      phase of VCI and the testing of novel interventional strategies.

PMID- 14582453
TI  - Diabetes mellitus: a cardiovascular disease.
AB  - Cardiovascular disease (CVD) is the major cause of morbidity and mortality in
      patients with diabetes mellitus (DM). The pathophysiology of CVD in diabetes
      involves traditional and novel cardiac risk factors, including hypertension,
      dyslipidemia, smoking, genetic factors, hyperglycemia, insulin
      resistance/hyperinsulinemia, metabolic abnormalities, oxidative/glycoxidative
      stress, inflammation, endothelial dysfunction, a procoagulant state and
      myocardial fibrosis. Specific vascular, myopathic and neuropathic alterations
      have been suggested to be responsible for the excessive cardiovascular morbidity
      and mortality in diabetes. These alterations manifest themselves clinically as
      coronary heart disease, congestive heart failure and/or sudden cardiac death. In
      order to contain the emerging epidemic of CVD in DM, diabetic patients should
      ideally have excellent glycemic control, a low normal blood pressure and low
      levels of low-density lipoprotein cholesterol, and be taking an angiotensin
      converting enzyme inhibitor and aspirin, which may go some way to containing the
      emerging epidemic of CVD in DM.

PMID- 14582454
TI  - Acyl-coenzyme A:cholesterol acyltransferase inhibitors for controlling
      hypercholesterolemia and atherosclerosis.
AB  - Acyl-coenzyme A:cholesterol acyltransferase (ACAT; Sterol O-acyltransferase/SOAT)
      is an intracellular enzyme that catalyzes the formation of cholesteryl esters
      from cholesterol and fatty acyl-coenzyme A. ACAT inhibitors reduce plasma
      cholesterol levels by suppressing absorption of dietary cholesterol and by
      suppressing the assembly and secretion of apolipoprotein B-containing
      lipoproteins such as very low density lipoprotein in liver and chylomicron in
      intestine. Moreover, ACAT inhibitors prevent the conversion of macrophages into
      foam cells in the arterial walls. Thus, ACAT inhibitors are under investigation
      for controlling hypercholesterolemia and the development of atherosclerosis. Some
      potent ACAT inhibitors have been tested for their efficacy and safety in humans.

PMID- 14582455
TI  - Human apolipoprotein AI mimetic peptides for the treatment of atherosclerosis.
AB  - The effects of apolipoprotein (Apo) AI mimetic peptide synthesized from D- and L
      amino acids on atherosclerotic lesion formation were investigated in low-density
      lipoprotein (LDL) receptor-deficient mice on a Western diet and in apoE null
      mice. In addition, their effects on the inflammatory changes induced in LDL
      receptor mice fed a Western diet following influenza A infection were studied.
      When apolipoprotein AI mimetic peptides synthesized from either D- or L-amino
      acids were administered to LDL-receptor null mice, only peptides synthesized from
      D-amino acids were stable in the circulation and enhanced the ability of high
      density lipoprotein (HDL) to protect LDL against oxidation. Administration of the
      peptide D-4F to LDL-receptor null mice and apoE null mice decreased lesion size.
      Additionally, in LDL receptor null mice after influenza infection, D-4F treatment
      increased plasma HDL levels and paraoxonase activity, and inhibited increased in
      LDL-cholesterol and peak levels of interleukin-6 post-infection. Injection of
      female mice with male macrophages, and subsequent measurement of the male 'sry'
      gene, revealed a marked increase in macrophage traffic into the aortic arch after
      infection that was prevented by administration of D-4F. This indicates that: (i)
      oral D-4F has powerful anti-atherosclerotic properties, and (ii) the loss of the
      anti-inflammatory properties of HDL after influenza infection in mice is
      associated with increased arterial macrophage traffic that can be prevented by
      administration of D-4F.

PMID- 14582456
TI  - DX-9065a Daiichi.
AB  - DX-9065a is a Factor Xa inhibitor under development by Daiichi as an
      anticoagulant for the potential treatment of cardiovascular indications,
      including thrombosis and angina. By March 1996, DX-9065a had entered phase I
      trials in Japan and Europe, and by November 1998, it was in phase II trials in
      Japan. In February 2003, phase II trials for the prevention of myocardial
      infarction in patients with unstable angina pectoris were ongoing in Japan,
      Europe and the US.

PMID- 14582457
TI  - Fasidotril Eli Lilly.
AB  - Lilly is developing fasidotril, a diester prodrug of the active metabolite
      fasidotrilat, for the potential treatment of hypertension and congestive heart
      failure (CHF). Phase II trials to investigate the potential of fasidotril for the
      treatment of hypertension and CHF had commenced by the late 1990s, and were
      ongoing in July 2003 in the US and Europe.

PMID- 14582458
TI  - FM-VP4 Forbes Medi-Tech.
AB  - FM-VP4 is a phytosterol analog under development by Forbes Medi-Tech for the
      potential treatment of hyperlipidemia and hypercholesterolemia. By March 2002, FM
      VP4 had entered phase I clinical trials and phase II trials were underway by late
      2002.

PMID- 14582460
TI  - [Advances in the treatment of chronic viral hepatitis].

PMID- 14582459
TI  - NCX-4016 NicOx.
AB  - NCX-4016 is a nitric oxide-aspirin conjugate non-steroidal anti-inflammatory drug
      that is under investigation by NicOx for the potential treatment of
      cardiovascular disorders and colon cancer. In April 2002, a phase II clinical
      trial was initiated in symptomatic peripheral arterial disease, and in March
      2003, the University of Michigan was awarded a grant by the NIH to conduct a
      phase II trial in individuals at risk of colon cancer.

PMID- 14582462
TI  - [Clinical aspects and diagnosis of viral hepatitis].
AB  - Viral hepatitides are common diseases of modern man in both industrialized and
      developing countries, with a varying prevalence of particular types and mode of
      transmission. In current medicine, viral hepatitides are classified in the A-E
      nomenclature, differentiating viruses that can be etiologically defined with
      certainty on the basis of serum markers and hepatitides exhibiting all clinical
      and laboratory characteristics of viral hepatitis but of as yet nondemonstrable
      causative agents, classified in the non-A, non-E hepatitis group. Two issues are
      of high relevance in the pathogenesis of viral hepatitides: route of transmission
      (fecal-oral or parenteral) and basic mechanism of hepatocyte lesion. Although all
      hepatitis viruses replicate within the hepatocyte, the exact mechanism of
      hepatocyte necrosis has not yet been fully elucidated, i.e. direct cytotoxicity
      or hepatoprogressive immune response mediated primarily by the specific cytotoxic
      CD8 lymphocytes. Depending on the site of entry, the virus replicates in the
      adjacent lymphatic tissue for some time, followed by primary viremia, virus
      replication in the lymphoreticular organs (lymph nodes, liver, spleen), and
      eventual entry in the target cells--hepatocytes, accompanied by a varying grade
      of necrosis and inflammatory reaction. The clinical and laboratory signs of the
      disease correspond to the degree of liver necrosis and are not specific for
      particular types of viral hepatitis. The most frequent symptoms common to all
      types of viral hepatitis of moderate severity include elevated body temperature
      persisting for days, fatigue, gradual loss of appetite, nausea, dull pain and
      discomfort on DRL, vomiting, multiple loose stools, dark urine, jaundice of the
      skin and mucosa, and light stools. Generally, the ultimate outcome of the disease
      is elimination of the virus and complete recovery, however, a fulminant course
      with lethal outcome or transition to chronic disease may also occur, making viral
      hepatitides a major public health problem worldwide. In classical infectology,
      four clinical stages of the disease have been described: incubation or
      preclinical stage characterized by intensive virus replication; prodromal or
      preicteric stage with pronounced general symptoms of infection; icteric stage;
      and stage of recovery. The stages may show great interindividual variation in
      length and severity. The development of molecular technologies over the last
      decade has greatly contributed to better understanding of the pathogenesis of
      viral hepatitides and allowed for appropriate monitoring of the effect of
      antiviral therapy. However, major disadvantage of these tests is their high cost.
      The basic clinical characteristics of and diagnostic options for particular types
      of viral hepatitis are described, with special reference to the latest important
      concepts on the disease pathogenesis.

PMID- 14582461
TI  - [Therapy with interferon alfa and ribavirin in patients with chronic hepatitis C
      and normal levels of alanine aminotransferase].
AB  - The aim of the study was to evaluate the efficacy of combination therapy with
      interferon-alpha (IFN-alpha) and ribavirin in patients with chronic hepatitis C
      and normal alanine aminotransferase (ALT) values. In this retrospective study, 12
      HCV-RNA positive patients (7 males and 5 females, mean age 38.1 years), treated
      between 1998 and 2001, with normal or near normal ALT values on three consecutive
      occasions and histologically mild disease were identified. During the induction
      period of four weeks they received 56 MU IFN-alpha 2b and ribavirin 1000 mg
      daily. During the next 44 weeks they received 3 MU IFN-alpha 2b three times a
      week with ribavirin 1000 mg daily. Seven out of 12 (58%) patients were HCV-RNA
      negative at the end of the therapy (end-of-treatment-response) and 5 of 12 (42%)
      showed sustained virologic response at 6 months. No significant elevation of
      aminotransferase values was recorded during therapy. Patients with mild chronic
      hepatitis C and normal ALT levels respond well to combination therapy with
      interferon and ribavirin, similar to those with elevated ALT levels. As long as
      the natural history and long-term outcome of these patients are not completely
      known, this might be a beneficial treatment option.

PMID- 14582463
TI  - [Treatment of viral hepatitis].
AB  - The primary goals of treatment for viral hepatitis are to eradicate the infection
      early in the course of the disease, to prevent progression to end-stage liver
      disease, and to prevent the development of hepatocellular carcinoma. The
      secondary goal is to decrease the number of chronic carriers who serve as a
      reservoir for viral transmission. The major step in the management of hepatitis B
      was the introduction of successful vaccination. The treatment of hepatitis B
      includes nucleoside analogues (lamivudine and adefovir) and interferon. The major
      problem in lamivudine treatment is the development of resistant viral mutants.
      Hepatitis D can worsen hepatitis B and lead to progressive liver disease. The
      recommended treatment is interferon. Hepatitis C, due to the lack of vaccine and
      tendency to develop chronic liver disease, is the major health problem and the
      leading indication for liver transplantation today. The recommended treatment is
      the combination of pegylated interferon and ribavirin.

PMID- 14582464
TI  - [Clinical aspects and therapy of toxic hepatitis].
AB  - The different types of hepatotoxicity can be induced by drugs. Approximately 2%
      5% of patients require hospitalization for jaundice. Drug-induced hepatic lesions
      are responsible for 10% of hepatitis cases in adults. Most hepatotoxic drug
      reactions are idiosyncratic and classified either as immunologic
      (hipersensitivity) or metabolic. In contrast to intrinsic hepatotoxins, these
      reactions are not dose-dependent nor predictable. The enzyme system responsible
      for drug biotransformation in liver is cytochrome P450, a large multigene family
      of enzymes with 300 members. Clinical presentation in patients who develop drug
      hepatotoxicity can be asymptomatic with mild biochemical abnormalities,
      resembling acute hepatitis or chronic autoimmune hepatitis, veno-occlusive
      disease and cirrhosis. Withdrawal of the drug usually leads to reversal of the
      lesion. A spectrum of drug induced hepatotoxicity, diagnosis and treatment is
      reviewed.

PMID- 14582465
TI  - [Non-alcoholic steatohepatitis].
AB  - Nonalcoholic steatohepatitis (NASH) is a condition characterized histologically
      by macrovesicular steatosis and lobular hepatitis with necrosis or ballooning
      degeneration and/or fibrosis--a picture resembling alcoholic hepatitis, in the
      absence of alcohol abuse. Most patients with NASH are asymptomatic, and the
      disease is detected incidentally. The most common signs of NASH are hepatomegaly
      and laboratory abnormalities, which include a 2-4-fold elevation of serum
      aminotransferase levels, while other liver function test results are usually
      normal. Most patients with NASH are obese, many have diabetes mellitus,
      hypercholesterolemia, or hypertriglyceridemia. NASH has also been associated with
      a number of metabolic derrangements, conditions, surgical procedures, and drug
      treatments. The pathogenesis of NASH is poorly understood, but lipid peroxidation
      and oxidative stress seem to be the leading culprits. The natural history of NASH
      is unknown, but it seems to be a stable disease in most patients. Still, the
      progress to cirrhosis is possible. There is no established treatment for NASH.
      Treatment is usually directed towards optimizing body weight, and pharmacologic
      agents are mostly experimentally used. Orthotopic liver transplantation is the
      treatment of choice for end-stage liver disease secondary to NASH.

PMID- 14582466
TI  - [Autoimmune hepatitis].
AB  - Autoimmune hepatitis is an unresolving, hepatocellular inflammation of unknown
      cause that is characterized by the presence of periportal hepatitis on histologic
      examination, tissue autoantibodies in serum, and hypergammaglobulinemia. By
      international consensus, the designation autoimmune hepatitis has replaced
      alternative terms for the condition. Three types of autoimmune hepatitis have
      been proposed based on immunoserologic findings. Type 1 autoimmune hepatitis is
      characterized by the presence of antinuclear antibodies (ANA) or smooth muscle
      antibodies (SMA) (or both) in serum. Seventy percent of patients with type 1 of
      autoimmune hepatitis are women. This type is the most common form and accounts
      for at least 80% of cases. Type 2 is characterized by the presence of antibodies
      to liver-kidney microsome type 1 (anti-LKM1) in serum. Patients with this type of
      autoimmune hepatitis are predominantly children. Type 3 autoimmune hepatitis is
      characterized by the presence of antibodies to soluble liver antigen (anti-SLA)
      in serum. There are no individual features that are pathognomonic of autoimmune
      hepatitis, and its diagnosis requires the confident exclusion of other
      conditions. The large majority of patients show satisfactory response to
      corticosteroid (usually prednisone or prednisolone) therapy. For the past 30
      years it has been customary to add azathioprine as a "steroid sparing" agent to
      allow lower doses of steroids to be used and remission, once achieved, can be
      sustained in many patients with azathioprine alone after steroid withdrawal.
      Patients with autoimmune hepatitis who have decompensated during or after
      corticosteroid therapy are candidates for liver transplantation.

PMID- 14582468
TI  - [Primary biliary cirrhosis].
AB  - Primary biliary cirrhosis is an autoimmune chronic cholestatic liver disease of
      unknown cause that usually affects middle-aged women. It is characterized by
      inflammatory destruction of the interlobular and septal bile ducts, which leads
      to chronic cholestasis and cirrhosis. The diagnosis should be considered in the
      setting of elevated alkaline phosphatase, immunoglobulin M level and the presence
      of antimitochondrial antibody in serum. Ursodeoxycholic acid is the only
      medication of proven benefit for these patients. Liver transplantation is only
      therapeutic option for patients who have end-stage disease.

PMID- 14582469
TI  - [Wilson's disease].
AB  - Wilson's disease is an autosomal recessive disorder of copper metabolism. The
      Wilson disease protein is a copper-transporting P-type ATPase, ATP7B, the
      malfunction of which results in the toxic accumulation of copper in the liver and
      brain, causing the hepatic and/or neurological symptoms accompanying this
      disease. Patients present, generally between the ages of 10 and 40 years, with
      liver disease, neurological disease of a movement disorder type, or behavioral
      abnormalities, and often with a combination of these. Because Wilson's disease is
      effectively treated, it is extremely important for physicians to learn to
      recognize and diagnose the disease. The laboratory diagnosis of Wilson's disease
      is confirmed by decreased serum ceruloplasmin, increased urinary copper content,
      and elevated hepatic copper concentration. Molecular genetic analysis is complex
      as more than 200 unique mutations have been identified and most individuals are
      compound heterozygotes. The treatment of Wilson's disease must be life long.
      Copper chelation with penicillamine is an effective therapy in most patients.
      Another chelating agent which has been used successfully as the initial therapy
      is trientine. The search for new anticopper drugs for Wilson's disease is
      culminating in two excellent new drugs: zinc for maintenance therapy and ammonium
      tetrathiomolybdate (which is to date still an experimental drug) for initial
      therapy. Liver transplantation is indicated for the fulminant form and in those
      patients with severe disease not responding to optimal medical management. This
      paper reviews the pathogenesis, pathology, clinical presentation and diagnosis of
      the Wilson's disease as well as the most recent views on the molecular genetics
      and the treatment of this disease.

PMID- 14582467
TI  - [Primary sclerosing cholangitis--diagnosis and therapy].
AB  - Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of
      unknown origin, characterized by inflammation, fibrosis, and obliteration of bile
      ducts, which ultimately results in biliary cirrhosis. The condition most commonly
      affects intrahepatic and extrahepatic bile ducts together, but sometimes only
      intrahepatic or extrahepatic ducts are involved. PSC is often associated with
      inflammatory bowel disease, especially ulcerative colitis. The majority of
      patients are initially asymptomatic, and identified on the basis of elevated
      serum levels of alkaline phosphatase or gamma-glutamyl transpeptidase, especially
      while screening patients with ulcerative colitis. Diagnosis is based on
      characteristic cholangiographic appearance with focal bile duct dilatations
      proximal to areas of stricturing that produce a beaded appearance.
      Ursodeoxycholic acid is most effective medical therapy, with other symptomatic
      measures, while liver transplantation is the treatment of choice for patients
      with advanced liver disease.

PMID- 14582470
TI  - [Hereditary hemochromatosis--diagnostic and therapeutic options].
AB  - Hereditary hemochromatosis is an autosomal recessive disorder resulting in iron
      overload. A progressive increase in total body iron stores leads to deposition of
      iron in parenchymal organs and to subsequent damage to these organs. The
      identification of the HFE gene and its mutations has stimulated much additional
      interest in this under-recognized but evidently treatable chronic disease. The
      goal for diagnosing the disease is to identify presymptomatic patients who will
      respond more favorably to phleobotomy which may prevent future chronic disease.

PMID- 14582471
TI  - [Therapy of malignant liver tumors].
AB  - The management of hepatic malignancy is one of the most controversial areas in
      medicine today. The most recent developments in technology, surgical methods,
      local treatment and neoadjuvant cancer therapy, have contributed significantly to
      improved results of treatment. A multidisciplinary approach including
      oncologists, hepatobiliary surgeons, radiotherapists, interventional radiologists
      and in few cases transplant surgeons, is important to advance the treatment
      outcomes. Although all the methods of treatment mentioned above add significantly
      to the prognosis of the disease, its early detection allows fotchoosing the
      optimal method and remains the key factor in the disease outcome. The aim of this
      paper is to review recent literature on the multimodal approaches to the
      treatment of the two most common primary carcinomas of the liver--hepatocellular
      carcinoma (HCC) and cholangiocarcinoma (CCC), as well as metastasis to the liver
      predominantly derived from colorectal cancer.

PMID- 14582472
TI  - [Caroli's disease].
AB  - Caroli's disease is a rare condition characterized by congenital polycystic
      dilatation of the intrahepatic bile ducts. The most frequent clinical
      presentation of a simple type (Caroli's disease) is recurrent cholangitis,
      gallstone with pain, obstructive jaundice and episodes of pancreatitis in
      childhood and early adulthood. A more frequent type combined with congenital
      hepatic fibrosis is usually manifested with bleeding from esophageal varices
      consequential to portal hypertension. Treatment options, both conservative and
      surgical, are relatively limited and depend on the clinical presentation,
      localization of cysts in the liver, and stage of the disease. A 20-year-old man
      with Caroli's disease manifested with cholelithiasis and choledocholithiasis with
      recurrent pancreatitis at the age of 16 is presented. The diagnosis was confirmed
      by endoscopic retrograde cholangiopancreatography and magnetic resonance
      cholangiopancreatography. Treatment with ursodeoxycholic acid was initiated and
      after two years of follow-up the disease is stable.

PMID- 14582474
TI  - [In memoriam Heinz Rollhauser (1919-2003)].

PMID- 14582473
TI  - [Macrophage colony-stimulating factor (M-CSF) as a candidate for the tumor marker
      of breast cancer].
AB  - Macrophage--colony stimulating factor (M-CSF) is one of the glycoproteins called
      colony-stimulating factors (CSFs). Some clinical investigations have shown
      autologous production of M-CSF various human cell lines in vitro and by tumors in
      vivo. We have investigated the plasma level of M-CSF and commonly accepted tumour
      markers, such as CA 15-3 in breast cancer. The plasma levels of cytokines were
      measured in 30. patients with breast cancer before surgery and 20. healthy
      subjects. The patients were divided into two groups: A (stage I) and B (stage
      II). M-CSF was determined using enzyme-linked immunosorbent assay (ELISA), CA 15
      3 was measured by microparticle enzyme immunoassay (MEIA). Mean M-CSF and CA 15-3
      plasma levels were significantly higher in breast cancer patients compared to the
      control group. The M-CSF level was significantly higher (statistical
      significance) in group B (II stage) when compared to group A (I stage) and group
      B to control group. The diagnostic sensitivity of M-CSF were related to the stage
      of disease (group A--10%, group B--40%) and combined use with CA 15-3 (group A-
      30%, group B--65%). These results suggest a potential role for M-CSF as tumour
      marker for breast cancer.

PMID- 14582475
TI  - Clinical quiz. Leiomyoma.

PMID- 14582476
TI  - Extension defects after ACL reconstructions, PCL lesions and tendinosis
      treatment.

PMID- 14582477
TI  - The Commission's policy on the environment.

PMID- 14582478
TI  - Doris' visit.

PMID- 14582479
TI  - 2nd Annual Conference on Cardiac Safety of New Drug Products: Philadelphia, PA,
      USA, March 24-25, 2003.

PMID- 14582480
TI  - Growing old gracefully.

PMID- 14582481
TI  - STROKE: From Bench to Bedside ASPET-Ray Fuller Symposium: San Diego Marriott
      Hotel, San Diego, CA, USA, April 10-11, 2003.

PMID- 14582482
TI  - Emerging Cardiovascular Therapeutics. Cambridge, MA, USA, June 10-11, 2003.

PMID- 14582484
TI  - Current awareness in human psychopharmacology.

PMID- 14582483
TI  - Reliability of a Smoking Cessation Risk Factor Interview Scale (SCRFIS) for use
      with standardized patient instructors.
AB  - BACKGROUND: This study evaluated internal consistency and inter-rater reliability
      of the smoking cessation risk factor interview scale (SCRFIS). METHODS:
      Encounters from 16 patient instructors and 414 medical students were used for
      analyses: Cronbach's alpha and item-to-total correlations measured internal
      consistency; one-way analysis of variance evaluated comparability of scores
      across multiple raters, t-tests measured gender bias, and regression analyses
      compared student counseling skills across three curricula. RESULTS: The total
      scale was reliable, there was minimal gender bias, and student counseling skills
      remained relatively constant over time. Interviewing techniques, however,
      improved among students who participated in the curriculum that emphasized
      earliest patient contact. CONCLUSION: A preliminary assessment of the measurement
      adequacy of the SCRFIS suggests that this instrument is a reliable measure of
      medical student's counseling skills on smoking cessation and is sensitive to
      changes in curriculum that emphasize patient contact. The SCRFIS may be applied
      in undergraduate medical curriculum, but it is advisable to evaluate the
      psychometric properties of this scale when used as an assessment of student
      performance.

PMID- 14582485
TI  - AMDA Foundation research network.

PMID- 14582486
TI  - How to deal with difficult and manipulative clients.

PMID- 14582488
TI  - Pain and symptom management.

PMID- 14582487
TI  - A case report of migration of buffers to the cecum following Stamey operation.

PMID- 14582489
TI  - [50th annual meeting of the Japanese Society of Clinical Pathology. Hiroshima,
      Japan. October 28-31, 2003. Program and Abstracts].

PMID- 14582491
TI  - [Regional meeting of the Japanese Society of Otolaryngology. Japan. 2002.
      Abstracts].

PMID- 14582490
TI  - Lack of correlation between SREBF1 genotype and hyperlipidemia in individuals
      treated with highly active antiretroviral therapy.

PMID- 14582492
TI  - Competitive and interactions affecting a fermentative spirochete in anaerobic
      chemostats.
AB  - Terminal restriction fragment length polymorphism and fluorescent in situ
      hybridization revealed that spirochete-related populations dominated two glucose
      fed methanogenic bioreactor communities at dilution rates of 0.06, 0.13, and 0.17
      day(-1). At dilution rates of 0.25 and 0.50 day(-1), spirochete-related
      populations decreased while Clostridium-related populations increased. Isolates
      representing both dominant populations were obtained (Treponema R8 and
      Clostridium S9) and competed against each other in continuous culture. Treponema
      R8 out-competed Clostridium S9 at all dilution rates applied (0.17 to 1.0 day(
      1)) when sufficient pantothenate was supplied in the medium. Without sufficient
      pantothenate, the population size of Treponema R8 was limited to 40% of the total
      cells. Coculture of Treponema R8 with Methanobacterium bryantii increased the
      cell yield of Treponema R8 and relieved the pantothenate requirement. Triculture
      of Treponema R8, Clostridium S9, and M. bryantii in pantothenate-deficient medium
      allowed Treponema R8 to outcompete Clostridium S9 in continuous culture upto a
      dilution rate of 0.50 day(-1). These experiments demonstrate that cofactor and
      vitamin requirements can affect the competitive success of a microbial species.

PMID- 14582493
TI  - [To get admission fast -- to create job-sharing partnership?].

PMID- 14582494
TI  - The difficult task of family caregiving in oncology: exactly which roles do
      autonomy and gender play?

PMID- 14582495
TI  - [Introduction of the DRG-based reimbursement system at the Hannover Clinic].

PMID- 14582496
TI  - Exploring bacteriplankton growth and protein synthesis to determine conversion
      factors across a gradient of dissolved organic matter.
AB  - The effect of bacterial specific growth rates of abundance (micro) and protein
      synthesis (b) on conversion factor (CF) variability was explored in order to
      provide an alternative approach to the controversial application of just one
      universal CF to field data. Nine regrowth cultures (RCs) were set up from very
      diverse aquatic ecosystems, controlling temperature and adding N and P to avoid
      mineral limitation and force organic carbon limitation. The values of micro
      varied one order of magnitude from 0.26 to 3.34 d(-1), whereas b values varied
      two orders of magnitude from 0.28 to 34.87 d(-1). We found no relationships
      between micro or b values and the dissolved organic carbon (DOC) concentration or
      the dissolved organic matter (DOM) quality indexes assayed. Abundance and protein
      synthesis increased exponentially and synchronously in four RCs, leading to
      balanced growth (micro = b). In contrast, abundance and protein synthesis
      increased logistically in the other five RCs and b values were significantly
      higher than g values, leading to unbalanced growth (micro not equal b). CFs
      ranged from 0.0062 to 0.0576 x 10(18) cells mol leucine(-1) with an average of
      0.0305 x 10(18) cells mol leucine(-1). CFs obtained in RCs with balanced growth
      were generally higher than CFs obtained in RCs with unbalanced growth and were
      not alike, impeding the establishment of an upper limit for CFs. A positive and
      significant relationship (n = 8, p < 0.0 1, r2 = 0.71) was found between CFs and
      DOC concentration (CF (x10(18) cells mol leucine(-1)) = 0.0104 + 0.0094 DOC (mM))
      when the value for the most productive system was excluded. This function permits
      the estimation of site-specific CFs based on DOC concentration instead of the
      controversial use of a single CF for different systems.

PMID- 14582497
TI  - Krischer v. McIver: avoiding the dangers of assisted suicide.

PMID- 14582498
TI  - Genes out of the bottle.

PMID- 14582499
TI  - Observers' reactions to genetic testing: the role of hindsight bias and
      judgements of responsibility.
AB  - In 3 studies, we examined the effect of birth outcome on observers' reactions to
      genetic testing. Participants read a scenario in which a woman declined to take a
      genetic screening test and subsequently gave birth to a child with a genetic
      disorder (negative outcome) or a healthy child (positive outcome). Retrospective
      judgments of the likelihood that the child would have a genetic disorder were
      higher given negative than positive outcome knowledge under conditions of high
      genetic risk. Moreover, the more likely a negative outcome was perceived to be,
      the more responsible the mother was held for not taking the genetic screening
      test. Consistent with Weiner's (1993) theory, responsibility judgments were
      linked to displeasure and sympathy, with sympathy in turn being related to help
      judgments.

PMID- 14582500
TI  - An internalist view on the value of life and some tricky cases relevant to it.
AB  - If we understand death as the irreversible loss of the good life, we can give
      meaning to the idea that for suffering patients in the end stage of their
      illness, life may become an evil and death no longer a threat. Life may lose its
      good already in the living person. But what does the good of life consist in,
      then? I defend an internalist view according to which the goodness of life is
      intrinsically related to the attitudes, concerns, interests and experiences of
      the person who is leading the life. This results in the contention that the core
      of what we understand as the value of the person's life is to be identified with
      what makes life go well for the person living the particular life. This
      internalist view does not presuppose (or imply) hedonism or mentalism, nor does
      it pose an experience requirement. Something may be good for you, because it is
      valuable as seen from your authentic viewpoint, even if you do not actually
      experience this goodness, or think otherwise because you are mistaken about your
      own well-being. To test this position, and the authenticity-requirement it
      includes, I discuss three cases of patients who are persistent in denying that in
      their life any value is left and who contend that death is not worse than further
      living. Internalism acknowledges that in the life of these patients there may be
      'functionings' and 'beings' that are worthwhile, where the test of value is at
      least partially independent of subjective assessment. Still, internalism claims
      that something truly valuable can only contribute to the good of one's life of it
      has positive meaning as seen from the attitudinal viewpoint that identifies
      oneself.

PMID- 14582501
TI  - Embryos, individuals, and persons: an argument against embryo creation and
      research.
AB  - One strategy for arguing that it should be legally permissible to create human
      embryos, or to use spare human embryos, for scientific research purposes involves
      the claim that such embryos cannot be persons because they are not human
      individuals while twinning may yet take place. Being a human individual is
      considered to be by most people a necessary condition for being a human person. I
      argue first that such an argument against the personhood of embryos must be
      rationally conclusive if their destruction in public places such as laboratories
      is to be countenanced. I base this argument on a popular understanding of the
      role that the notion of privacy plays in abortion laws. I then argue that such
      arguments against personhood are not rationally conclusive. The claim that the
      early embryos is not a human individual is not nearly as obvious as some assert.

PMID- 14582502
TI  - Changes in body temperature and basal metabolic rate of the Ama. 1963.

PMID- 14582503
TI  - Two kinds of potentiality: a critique of McGinn on the ethics of abortion.
AB  - In Moral Literacy, or How to Do the Right Thing, Colin McGinn proposes a
      consequentialist solution to the abortion dilemma. McGinn interprets moral rights
      and moral interests as attributable only to actually sentient beings by virtue of
      their ability to experience pleasure or pain. McGinn argues against the moral
      rights of potentially conscious human fetuses, on the grounds that the unjoined
      ova and spermatoza of any fertile men and women are also potentially sentient,
      but we do not generally suppose that unjoined human genetic germ plasm has moral
      rights. I argue that McGinn's reply equivocates between two different senses of
      'potential sentience.' I distinguish between strong and weak potentiality, or
      between naturally probably potentiality and merely logically possible
      potentiality. I agree that it is reasonable to deny that a weak or merely
      logically possible potentially sentient fetus that would result from any unjoined
      ovum and sperm has a moral right to life. But I claim that this fact does not
      diminish the plausibility of extending a moral right or potential moral right to
      life to a naturally probable potentially sentient fetus, which we have good
      reason to believe will actually become sentient in the natural course of things
      if nothing is done to prevent its normal development. I conclude that it is not
      merely the potentiality, but the strong potentiality of a healthy, normally
      developing fetus that is soon to acquire sentience, moral interests, and, on
      McGinn's own terms, a moral right to life, that continues to sustain the abortion
      controversy, even among those who also want respect a woman's right to
      reproductive self-determination.

PMID- 14582504
TI  - [Quality control of culture media for mycobacterium drug sensitivity tests].

PMID- 14582505
TI  - [Standards for diagnosis of non-tuberculous mycobacteria infections].

PMID- 14582507
TI  - Medical image. Capsule endoscopy.

PMID- 14582506
TI  - Medical image. The nitty gritty testicle.

PMID- 14582508
TI  - Abstracts of the 22nd Workshop of the Study Group on Artificial Insulin Delivery,
      Pancreas and Islet Transplantation (AIDPIT) of the European Association for the
      Study of Diabetes (EASD). Igls, Austria, January 26-28, 2003.

PMID- 14582509
TI  - Abstracts of the International Society of Non-Invasive Cardiology, 19th European
      Congress. May 8-10, 2003, Istanbul, Turkey.

PMID- 14582510
TI  - Modified procedure of minimally invasive direct coronary artery bypass grafting
      using the left internal thoracic artery--radial artery composite graft.

PMID- 14582511
TI  - A hydrothermal system associated with the Siljan impact structure, Sweden-
      implications for the search for fossil life on Mars.
AB  - The Siljan ring structure (368 +/- 1.1 Ma) is the largest known impact structure
      in Europe. It isa 65-km-wide, eroded, complex impact structure, displaying
      several structural units, including a central uplifted region surrounded by a
      ring-shaped depression. Associated with the impact crater are traces of a post
      impact hydrothermal system indicated by precipitated and altered hydrothermal
      mineral assemblages. Precipitated hydrothermal minerals include quartz veins and
      breccia fillings associated with granitic rocks at the outer margin of the
      central uplift, and calcite, fluorite, galena, and sphalerite veins associated
      with Paleozoic carbonate rocks located outside the central uplift. Two-phase
      water/gas and oil/gas inclusions in calcite and fluorite display homogenization
      temperatures between 75 degrees C and 137 degrees C. With an estimated erosional
      unloading of approximately 1 km, the formation temperatures were probably not
      more than 10-15 degrees C higher. Fluid inclusion ice-melting temperatures
      indicate a very low salt content, reducing the probability that the
      mineralization was precipitated during the Caledonian Orogeny. Our findings
      suggest that large impacts induce low-temperature hydrothermal systems that may
      be habitats for thermophilic organisms. Large impact structures on Mars may
      therefore be suitable targets in the search for fossil thermophilic organisms.

PMID- 14582515
TI  - e-Science.

PMID- 14582512
TI  - [Wilson-Mikity syndrome as a cause of respiratory insufficiency of prematurity].
AB  - The Wilson-Mikity syndrome is a differential diagnosis of chronic lung disease in
      the neonate and primarily related to immaturity. It is characterized by the
      absence of typical clinical and radiological findings of the respiratory distress
      syndrome (RDS). Infectious causes are being discussed.

PMID- 14582516
TI  - Computational analysis of mutation spectra.
AB  - Mutation frequencies vary along a nucleotide sequence, and nucleotide positions
      with an exceptionally high mutation frequency are called hotspots. Mutation
      hotspots in DNA often reflect intrinsic properties of the mutation process, such
      as the specificity with which mutagens interact with nucleic acids and the
      sequence-specificity of DNA repair/replication enzymes. They might also reflect
      structural and functional features of target protein or RNA sequences in which
      they occur. The determinants of mutation frequency and specificity are complex
      and there are many analytical methods for their study. This paper discusses
      computational approaches to analysing mutation spectra (distribution of mutations
      along the target genes) that include many detectable (mutable) positions. The
      following methods are reviewed: mutation hotspot prediction; pairwise and
      multiple comparisons of mutation spectra; derivation of a consensus sequence; and
      analysis of correlation between nucleotide sequence features and mutation
      spectra. Spectra of spontaneous and induced mutations are used for illustration
      of the complexities and pitfalls of such analyses. In general, the DNA sequence
      context of mutation hotspots is a fingerprint of interactions between DNA and DNA
      repair/replication/modification enzymes, and the analysis of hotspot context
      provides evidence of such interactions.

PMID- 14582517
TI  - Inferring gene networks from time series microarray data using dynamic Bayesian
      networks.
AB  - Dynamic Bayesian networks (DBNs) are considered as a promising model for
      inferring gene networks from time series microarray data. DBNs have overtaken
      Bayesian networks (BNs) as DBNs can construct cyclic regulations using time delay
      information. In this paper, a general framework for DBN modelling is outlined.
      Both discrete and continuous DBN models are constructed systematically and
      criteria for learning network structures are introduced from a Bayesian
      statistical viewpoint. This paper reviews the applications of DBNs over the past
      years. Real data applications for Saccharomyces cerevisiae time series gene
      expression data are also shown.

PMID- 14582518
TI  - Modelling protein functional domains in signal transduction using Maude.
AB  - Modelling of protein-protein interactions in signal transduction is receiving
      increased attention in computational biology. This paper describes recent
      research in the application of Maude, a symbolic language founded on rewriting
      logic, to the modelling of functional domains within signalling proteins. Protein
      functional domains (PFDs) are a critical focus of modern signal transduction
      research. In general, Maude models can simulate biological signalling networks
      and produce specific testable hypotheses at various levels of abstraction.
      Developing symbolic models of signalling proteins containing functional domains
      is important because of the potential to generate analyses of complex signalling
      networks based on structure-function relationships.

PMID- 14582519
TI  - An overview of data models for the analysis of biochemical pathways.
AB  - Biochemical pathways such as metabolic, regulatory or signal transduction
      pathways can be viewed as interconnected processes forming an intricate network
      of functional and physical interactions between molecular species in the cell.
      The amount of information available on such pathways for different organisms is
      increasing very rapidly. This is offering the possibility of performing various
      analyses on the structure of the full network of pathways for one organism as
      well as across different organisms, and has therefore generated interest in
      developing databases for storing and managing this information. Analysing these
      networks remains far from straightforward owing to the nature of the databases,
      which are often heterogeneous, incomplete or inconsistent. Pathway analysis is
      hence a challenging problem in systems biology and in bioinformatics. Various
      forms of data models have been devised for the analysis of biochemical pathways.
      This paper presents an overview of the types of models used for this purpose,
      concentrating on those concerned with the structural aspects of biochemical
      networks. In particular, the different types of data models found in the
      literature are classified using a unified framework. In addition, how these
      models have been used in the analysis of biochemical networks is described. This
      enables us to underline the strengths and weaknesses of the different approaches,
      as well as to highlight relevant future research directions.

PMID- 14582520
TI  - Computational knowledge integration in biopharmaceutical research.
AB  - An initiative to increase biopharmaceutical research productivity by capturing,
      sharing and computationally integrating proprietary scientific discoveries with
      public knowledge is described. This initiative involves both organisational
      process change and multiple interoperating software systems. The software
      components rely on mutually supporting integration techniques. These include a
      richly structured ontology, statistical analysis of experimental data against
      stored conclusions, natural language processing of public literature, secure
      document repositories with lightweight metadata, web services integration,
      enterprise web portals and relational databases. This approach has already begun
      to increase scientific productivity in our enterprise by creating an
      organisational memory (OM) of internal research findings, accessible on the web.
      Through bringing together these components it has also been possible to construct
      a very large and expanding repository of biological pathway information linked to
      this repository of findings which is extremely useful in analysis of DNA
      microarray data. This repository, in turn, enables our research paradigm to be
      shifted towards more comprehensive systems-based understandings of drug action.

PMID- 14582521
TI  - Hydropathy--a window on the evasion of water.

PMID- 14582522
TI  - Shopping in the genome market with EnsMart.
AB  - Life scientists who work with the supermarket of genome data will find the
      EnsMart database and software package offers a valuable door to a wealth of genes
      and genome features. Not only available to lab biologists on the web, this
      popular multi-organism genome database can be installed and used on your own Unix
      computer with relative ease. It offers a flexible, fast and practical data-mining
      framework for computer-savvy biologists and bioinformaticians.

PMID- 14582523
TI  - The New Freedom Initiative and its impact on disability and rehabilitation
      research.

PMID- 14582524
TI  - Neck range of motion and use of computer head controls.
AB  - Head controls provide an alternative means of computer access. This study
      determined whether neck movement limitations are associated with reduced
      performance with such head controls. This study also identified features of the
      cursor movement path that could aid in assessing computer access limitations.
      Fifteen subjects without disabilities and ten subjects with disabilities received
      neck range of motion evaluations and performed computer exercises using head
      controls. Reduced neck range of motion was correlated with reduced accuracy (R2 =
      93.5%) and speed (R2 = 79.5%) in icon selection. A model was developed with the
      use of cursor positioning time and number of velocity peaks to identify when a
      person was having difficulty with target acquisition (kappa = 0.81). Models such
      as this may allow head controls to adapt to a user's needs, accommodating
      difficulties resulting from neck range of motion limitations.

PMID- 14582525
TI  - Postoperative dressing and management strategies for transtibial amputations: a
      critical review.
AB  - Postamputation management is an important determinant of recovery from
      amputation. However, consensus on the most effective postoperative management
      strategies for individuals undergoing transtibial amputation (TTA) is lacking.
      Dressings can include simple soft gauze dressings, thigh-high rigid cast
      dressings, shorter removable rigid dressings, and prefabricated pneumatic
      dressings. Postoperative prosthetic attachments can be added to all but simple
      soft dressings. These dressings address the need to cleanly cover a fresh
      surgical wound, but not all postoperative dressings are designed to facilitate
      the strategic goals of preventing knee contractures, reducing edema, protecting
      from external trauma, or facilitating early weight bearing. The type of dressing
      and management strategy often overlap and are certainly interrelated. Current
      protocols and decisions are based on local practice, skill, and intuition. The
      current available literature is challenging, and difficulties include variations
      in healing potential, in comorbidity, in surgical-level selection, in techniques
      and skill, in experience with postoperative strategies, and with poorly defined
      outcome criteria. This paper reviews the published literature and compares
      measures of safety, efficacy, and clinical outcomes of the various techniques.
      Analysis of 10 controlled studies supported only 4 of the 14 claims cited in
      uncontrolled, descriptive studies.

PMID- 14582526
TI  - Bereitschaft (readiness potential) and supplemental motor area interaction in
      movement generation: spinal cord injury and normal subjects.
AB  - The readiness potential (BP) consists of movement-related cortical potentials
      (MRCPs) peaking in the motor potential (MP). Our objective was to better
      understand the role of the BP and MP in the production of voluntary movements and
      to help define the relative roles of the supplementary motor area (SMA) and the
      BP in the generation of self-paced and passive finger movements. The ultimate
      goal was to relate the BP (or the SMA) to external devices via conversion of
      potentials to a language "understood" by the receiving devices.

PMID- 14582527
TI  - Assessment of an electronic goniometer designed to measure equinus contracture.
AB  - To achieve more objective and repeatable measurements of equinus contracture, we
      developed the equinometer, a device that allows the measurement of ankle range of
      motion under controlled torque conditions. This study assessed its accuracy
      across different subjects and examiners. Two examiners used the equinometer to
      measure the angle of ankle dorsiflexion at 15 N x m torque on five subjects.
      Accounting for variation in measurements because of subjects, examiners, and
      placement of device, we used linear mixed-effects models. Accounting for the
      variation because of subject, different placements of the equinometer within each
      subject and the adjustment for the effects of examiner and trial sequence, the
      standard deviation was 0.94 degrees, 95% confidence interval (0.79 degrees, 1.13
      degrees). An upper standard deviation of 1.36 degrees is felt to be acceptable
      for clinical investigation.

PMID- 14582528
TI  - Long-term user perceptions of an implanted neuroprosthesis for exercise,
      standing, and transfers after spinal cord injury.
AB  - This study was completed to understand the usage patterns, system performance,
      degree of satisfaction, complications, and health benefits as perceived by
      recipients of a surgically implanted neuroprosthesis for exercise, standing, and
      transfers in individuals with low-cervical or thoracic spinal cord injury (SCI).
      A standardized telephone survey was administered to 11 recipients of the Case
      Western Reserve University/Veterans Affairs (CWRU/VA) implanted standing
      neuroprosthesis with more than 12 months of experience with the functional
      electrical stimulation (FES) system. Nine implant recipients were using the
      neuroprosthesis regularly for standing and/or exercising at the time of the
      survey. All 11 implant recipients noted improved health and a reduced incidence
      of pressure sores, leg spasms, and urinary tract infections (UTIs). No incidents
      of deep-vein thrombosis, infection, cellulitis, or electrical burns because of
      the neuroprosthesis were noted. System recipients uniformly felt that the
      neuroprosthesis resulted in better overall health and general well-being.
      Subjects were moderately to very satisfied with the performance of the
      neuroprosthesis and unanimously expressed a willingness to repeat the surgery and
      rehabilitation to obtain the same clinical outcome. All implant recipients
      reported the system to be safe, reliable, and easy to use. The implanted standing
      neuroprosthesis appears to be a clinically acceptable and effective means of
      providing the ability to exercise, stand, and transfer to selected individuals
      with paraplegia or low tetraplegia.

PMID- 14582529
TI  - Reliability of computer-automated hearing thresholds in cochlear-impaired
      listeners using ER-4B Canal Phone earphones.
AB  - This paper describes the second phase of a study to determine test-retest
      reliability of hearing thresholds using a computer-automated technique with ER-4B
      Canal Phone insert earphones. The first phase documented reliable hearing
      thresholds in 20 normal-hearing individuals. For this second phase, 20
      individuals with cochlear hearing loss completed the same testing protocol as for
      phase one. During each of two sessions, hearing thresholds were obtained in one
      third octave steps at 500 Hz to 16,000 Hz. The octave frequencies were
      immediately retested, followed by ear-tip reinsertion and further retesting at
      octave frequencies. Both groups showed overall good threshold reliability, with
      observable differences between groups. First, repeated testing resulted in
      improved hearing thresholds for the normal-hearing group, but not for the
      cochlear-loss group. Second, the normal-hearing group showed overall better
      response reliability, both within and between sessions, than the cochlear-loss
      group. These differences were small but consistent.

PMID- 14582530
TI  - Telemedicine and the delivery of health services to veterans with multiple
      sclerosis.
AB  - Telemedicine involves the provision of health care and sharing of medical
      knowledge using telecommunications technologies. Preventive, diagnostic, and
      therapeutic services, as well as patient education and assistance with self
      management of health, can be provided via telemedicine. The Veterans Health
      Administration (VHA) has a wide range of telemedicine capabilities. Given
      limitations on studying its effectiveness, telemedicine is often applied to new
      patient populations without explicit evaluation of efficacy. Evaluating the
      potential use of telemedicine services through supporting literature from other
      disorders may be possible. This paper discusses applying telemedicine to the care
      of individuals with multiple sclerosis (MS) when few published evaluations exist
      in MS. In this paper, we (1) provide a background on the use of telemedicine in
      the private sector and in the VHA, (2) discuss the use of current telemedicine
      literature to management of individuals with MS, and (3) review the strengths and
      limitations of telemedicine as a care delivery vehicle.

PMID- 14582531
TI  - A comparison of cutaneous vascular responses to transient pressure loading in
      smokers and nonsmokers.
AB  - Smoking has been recognized as a risk factor for pressure ulcer development. This
      study investigated the hypothesis that smoking causes alterations in cutaneous
      vascular perfusion, which may contribute to this increased risk. With the use of
      the laser Doppler fluximetry (LDF), the adaptive vasodilatory response to a
      transient pressure load at the sacrum was measured in nine healthy female smokers
      and their age, sex, body mass index (BMI), and menstrual cycle matched nonsmoker
      controls. In all subjects, removal of the pressure load resulted in a reactive
      hyperaemic response. The total hyperaemic response was approximately 45% smaller
      in smokers compared to nonsmoker controls. The reduction was due to a shortening
      of the duration of the response predominantly through an increase in the rate of
      recovery from peak, which was twice as fast in the smokers (2.4 +/- 1.7 AU x
      seconds) compared with the nonsmoking controls (1.1 +/- 0.9 AU x seconds) (p <
      0.005). We conclude that changes in the vascular responsiveness can be measured
      objectively at skin sites at risk of pressure ulcers. We have also shown that
      vascular responsiveness is altered in light smokers compared to control subjects.
      These preliminary data open the way for further investigation into the risk
      factors associated with pressure ulcer development.

PMID- 14582532
TI  - Mammalian telomeres and telomerase: why they matter for cancer and aging.
AB  - Chromosome ends, or telomeres, are formed by a special chromatin structure that
      protects them from recombination and degradation, thus preventing end-to-end
      chromosome fusions and other chromosomal aberrations. The functionality of
      telomeres, and that of the cellular activity that synthesizes them, telomerase,
      has been shown to impact on both cancer and aging, as well as on the organismal
      sensitivity to ionizing radiation. This review focuses on the analysis of
      different mouse models for proteins that are important for telomere function,
      which have highlighted the importance of telomeres and telomerase for cancer and
      aging.

PMID- 14582533
TI  - DAP-like kinase, a member of the death-associated protein kinase family,
      associates with centrosomes, centromers, and the contractile ring during mitosis.
AB  - DAP-like kinase (Dlk) is a nuclear serine/threonine-specific kinase which has
      been implicated in apoptosis. However, induction of apoptosis by Dlk requires its
      relocation to the cytoplasm, particularly association with the actin
      cytoskeleton, which is achieved through interaction with pro-apoptotic protein
      Par-4. On the other hand, nuclear Dlk does not induce apoptosis and has rather
      been implicated in transcription. To further explore the biological functions of
      Dlk, we established a cell clone of MCF-7 cells stably expressing a GFP-Dlk
      fusion protein at low level. Ectopic expression of GFP-Dlk did not affect the
      growth properties of the cells. During interphase, GFP-Dlk showed a diffuse
      nuclear distribution with punctate staining in a subpopulation of cells. During
      mitosis, however, Dlk was associated with centrosomes, centromeres, and the
      contractile ring, but not with the mitotic spindle. Association with centrosomes,
      as confirmed by colocalization with gamma-tubulin and pericentrin persisted
      throughout mitosis but was also seen in interphase cells. Interestingly, GFP-Dlk
      and gamma-tubulin could be co-immunoprecipitated indicating that they are present
      in the same protein complex. Association of Dlk with centromeres, as verified by
      confocal fluorescence microscopy with centromere-specific antibodies was more
      restricted and discernable from prophase to early anaphase. Centromere
      association of Dlk coincides with H3 phosphorylation at Thr11 that is
      specifically phosphorylated by Dlk in vitro (U. Preuss, G. Landsberg, K. H.
      Scheidtmann, Nucleic Acids Res. 31, 878-885, 2003). During cytokinesis, Dlk was
      enriched in the contractile acto-myosin ring and colocalized with Ser19
      phosphorylated myosin light chain, which is an in vitro substrate of Dlk.
      Strikingly, a C-terminal truncation mutant of Dlk generated multi-nucleated
      cells. Together, these data suggest that Dlk participates in regulation and,
      perhaps, coordination of mitotis and cytokinesis.

PMID- 14582535
TI  - Tropomyosin 4 expression is enhanced in dedifferentiating smooth muscle cells in
      vitro and during atherogenesis.
AB  - Dedifferentiation of smooth muscle cells (SMC) from the contractile to the
      synthetic phenotype is a key event in atherosclerosis. A comparable phenotypic
      change from the contractile to the synthetic state is rapidly incurred when SMC
      are grown in culture. To identify genes that characterize the contractile and
      synthetic phenotypes, we performed differential display reverse transcription
      polymerase chain reactions on RNA from porcine arterial contractile SMC obtained
      directly from medial tissues and from SMC made synthetic by cell culturing. One
      of the differentially expressed cDNAs we identified encoded tropomyosin 4 (TM4).
      Whereas basal levels of TM4 existed in contractile SMC, the amount of TM4
      transcripts strongly increased in synthetic SMC (33% vs. 86-106%; p < 0.005).
      Induction of foam cell formation had no additional enhancing effect on the
      expression of TM4 in cultivated SMC. We also tested whether TM4 expression was
      correspondingly enhanced during atherogenesis. The number of TM4-expressing SMC
      increased with plaque development as demonstrated by simultaneous in situ
      hybridization and immunohistochemistry. We compared the localization patterns of
      myosin heavy chain isoforms in normal arteries and lesions of increasing severity
      and determined that TM4 expression was relegated mainly to SMC of the synthetic
      phenotype in the media and intima during atherogenesis. The present study
      demonstrates that upregulation of TM4 mRNA is a relevant marker of
      dedifferentiation in vascular SMC.

PMID- 14582534
TI  - Origin of cortical microtubules organized at M/G1 interface: recruitment of
      tubulin from phragmoplast to nascent microtubules.
AB  - The origin of cortical microtubules (CMTs) was investigated in transgenic BY-2
      cells stably expressing a GFP (green fluorescent protein) -tubulin fusion protein
      (BY-GT16). In a previous study, we found that CMTs were initially organized in
      the perinuclear regions but then elongated to reach the cell cortex where they
      formed bright spots, and that the appearance of parallel MTs from the bright
      spots was followed by the appearance of transverse MTs (Kumagai et al., Plant
      Cell Physiol. 42, 723-732, 2001). In this study, we investigated the migration of
      tubulin to the reorganization sites of CMTs at the M/G1 interface. After
      synchronization of the BY-GT16 cells by aphidicolin, the localization of GFP
      tubulin was monitored and analyzed by deconvolution microscopy. GFP-tubulin was
      found to accumulate on the nuclear surface near the cell plate at the final stage
      of phragmoplast collapse. Subsequently, GFP-tubulin accumulated again on the
      nuclear surface opposite the cell plate, where nascent MTs elongated to the cell
      cortex. The significance of these observations on the mode of CMT organization is
      discussed.

PMID- 14582537
TI  - Surgical research.

PMID- 14582536
TI  - Genomic imbalances associated with methotrexate resistance in human osteosarcoma
      cell lines detected by comparative genomic hybridization-based techniques.
AB  - Methotrexate (MTX) is one of the most important drugs for osteosarcoma (OS)
      treatment. To identify genetic aberrations associated with the development of MTX
      resistance in OS cells, in addition to the previously reported expression changes
      of dihydrofolate reductase (DHFR) and reduced folate carrier (RFC) genes,
      comparative genomic hybridization (CGH)-based techniques were used. The direct
      comparison between MTX-resistant variants of U-2OS or Saos-2 human OS cell lines
      with their respective parental cell lines by CGH on chromosomes revealed that
      development of MTX resistance was associated with gain of the chromosomal regions
      5q12-q15 and 11q14-qter in U-2OS variants, and with gain of 8q22-qter in Saos-2
      variants. Further analyses by CGH on microarrays demonstrated a progressively
      increasing gain of mixed lineage leukemia (MLL) gene (11q23) in U-2OS MTX
      resistant variants, which was also confirmed by fluorescence in situ
      hybridization (FISH), in addition to gain of FGR (1p36),
      amplification/overexpression of DHFR, and slight decrease of RFC expression. In
      Saos-2 MTX-resistant variants, gain of MYC (8q24.12-q24.13) was detected,
      together with a remarkable decrease of RFC expression. Further analyses of DHFR,
      MLL, MYC, and RFC gene status in four additional human OS cell lines revealed
      that only gain of DHFR and MLL were associated with an inherent lower sensitivity
      to MTX. These data demonstrate that genetic analyses with complementary
      techniques are helpful for the identification of new candidate genes, which might
      be considered for an early identification of MTX unresponsive tumors.

PMID- 14582538
TI  - Advances in surgery of the newborn.

PMID- 14582539
TI  - Epidemiology of liver injuries.
AB  - BACKGROUND AND AIMS: The aim of this study was to investigate the epidemiology of
      liver injuries and to grade injuries according to the Organ Injury Scale in a
      population-based study in Stockholm County comprising 1.75 million inhabitants.
      MATERIAL AND METHODS: Cases were retrieved from the National Board of Forensic
      Medicine and Public Health and Medical Services Committee Register. Autopsy
      reports and patients files were studied for liver injuries, associated injuries,
      age, sex, trauma mechanism, location of the injury, description of the injury,
      diagnostic and treatment modalities when available. RESULTS: The incidence of
      traumatic liver injury in 1996 and 1997 was 2.95/100 000 annually. Seventy seven
      autopsies with liver injuries revealed injury pattern of grade I in 6 cases (8%),
      grade II in 10 cases (13%), grade III in 21 cases (27%), grade IV in 15 cases
      (19%), grade V in 16 cases (21%) and grade VI in 9 cases (12%). Twenty four
      patients revealed injury pattern of grade II in 13 cases (46%), grade III in 4
      cases (14%), grade IV in 5 cases (18%) and grade V in 2 cases (7%). CONCLUSIONS:
      The results demonstrate a low incidence of liver injuries in the studied
      population. Grade II and III injuries prevail. Surgical management of liver
      injuries is an infrequent treatment option in Stockholm County and simple
      operative measures were applied. No complex hepatic injuries were operated upon.

PMID- 14582540
TI  - Outcome and long term results of surgical resection for gastrointestinal stromal
      tumors (GIST).
AB  - BACKGROUND AND AIMS: Gastrointestinal Stromal Tumors (GIST) are rare; diagnosis
      and prognosis of these tumors are often complex. We present short and long term
      results of surgical resection for GIST at the Department of Surgery, University
      of Insubria, during a period of 14 years. MATERIAL AND METHODS: All patients'
      data, tumor characteristics, surgical procedure and survival data were analyzed
      retrospectively. Tumors were divided in risk classes using a new classification
      proposed by Fletcher, based on tumor size and number of mitosis. RESULTS: From
      1987 to 2001 19 patients underwent surgical resection for GIST. Stomach was the
      most common site of localization. Complete resection was achieved in 78.9 %
      cases, while in 21.1% radical resection was not possible. The mean tumor size was
      8.4 cm (1.2-30 cm): < 5 cm diameter in 11/19 cases (58%), 5-10 cm in 4/19 (21%)
      and > 10 cm in 4/19 (21%). Mitotic count was < 10/50 HPF in 68.5 % (13/19) and >
      10/50 in 31.5 % (6/19). Using Fletcher's classification, tumors were divided in
      very low (8/19, 42.2 %), low (3/19, 15.8 %), intermediate (4/19, 21%) and high
      risk (4/19, 21%). The 5 years overall survival was 63 % and 34 % respectively
      with a statistically significant difference between tumors < 5cm and > 10 cm in
      diameter and between complete and incomplete resection. High risk tumors have a
      significantly shorter survival than low or very low risk. CONCLUSIONS: Our
      experience confirms that GIST are uncommon and aggressive cancers which prognosis
      is strictly related to tumor size and number of mitosis. Although significant
      advances on new chemotherapic regimes have been made, to date, radical surgical
      removal is the only chance of long term survival.

PMID- 14582541
TI  - Laparoscopic billroth II gastrectomy for completely stricturing duodenal ulcer:
      technical details.
AB  - BACKGROUND: The authors report a series of three patients who underwent
      laparoscopic gastrectomy for gastric outlet obstruction due to stricturing
      duodenal ulcer. MATERIALS AND METHODS: In all cases an intracorporeal resection
      of the antrum and an antecolic end to side gastrojejunostomy (Billroth II) were
      performed. Technical details are discussed in the paper. RESULTS: Mean operative
      time was 260 minutes, mean blood loss was 43 millilitres. There were no
      postoperative complications and all patients were discharged on the fifth
      postoperative day. A follow up of three years shows that no patient had
      recurrence and post-gastrectomy syndromes. CONCLUSIONS: Laparoscopic Billroth II
      gastrectomy is a safe and feasible procedure with benefits such as quick hospital
      stay, decreased postoperative pain, good cosmesis and reduced morbidity.

PMID- 14582542
TI  - Common femoral artery--uncommon aneurysms.
AB  - BACKGROUND AND AIMS: Femoral artery aneurysms are rare. Their natural history,
      tendency to embolize or rupture are not well known. MATERIAL AND METHODS: Data of
      all patients seen 1996-2002 with femoral artery aneurysms at the Swiss
      Cardiovascular Center were analysed. Nine patients with 13 aneurysms of the
      common femoral artery (CFA) were identified. Only true aneurysms with a diameter
      of at least 2.5 cm were included. All patients were male, mean age 70 years
      (range: 57-85 years). Four patients had bilateral femoral aneurysms. Risk factors
      included hypertension (9/9), smoking (7/9). One of the aneurysms was palpable in
      5/9. Four patients were asymptomatic, 5 had Fontaine class II claudication. Five
      patients also had an aortic aneurysm (AAA), one a thoracic aneurysm; and 6/9
      popliteal aneurysms. In all patients, diagnosis was confirmed with duplex scan.
      Angiography was performed preoperatively. RESULTS: The aneurysms were operated on
      electively using aneurysm secclusion and interposition grafting. There were no
      significant perioperative complications. Median hospital stay was 8 days.
      CONCLUSION: CFA aneurysms are rare. They are palpable in nearly half of the
      cases. They rarely cause thrombotic or embolic complications, but are almost
      always connected to other aneurysms. Patients with CFA aneurysms should be
      screened with duplex scan. Operative therapy is straightforward, few
      complications can be expected. Postoperative follow-up with annual duplex scans
      is suggested.

PMID- 14582543
TI  - Is elective abdominal aortic aneurysm repair accompanied by high grade oxidative
      stress?
AB  - BACKGROUND AND AIMS: During elective abdominal aortic aneurysm repair (AAAR),
      lower torso ischaemia-reperfusion event is unavoidable. Previous studies on AAAR
      have reported the importance of oxidative stress (OS) in ischaemia-reperfusion
      injury, however, the grade of OS has not been adequately clarified up to now. The
      aim of this study was to perform a complex investigation of the time-course and
      grade of systemic and cellular OS in patients undergoing AAAR. MATERIAL AND
      METHODS: Arterial blood samples were taken from 18 patients undergoing elective
      AAAR (at four points in time: before anaesthesia, 5 min after aortic clamping and
      5 min and 30 min after clamp removal). Diene conjugates (DC), thiobarbituric acid
      reactive substances (TBARS), total antioxidative capacity (TAC), glutathione
      redox ratio (GSSG/GSH), and levels of antioxidative enzymes as superoxide
      dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSHPx) were measured
      from the radial arterial blood. RESULTS: 30 min after the removal of the aortic
      cross-clamp, arterial CAT showed significant elevation (96.0 vs 56.9 U/l, p <
      0.05); GSHPx was significantly elevated (51.5 vs 39.9 U/g Hgb, p < 0.05) and TAC
      was decreased (31.4 vs 36.5%, p < 0.05) in comparison with preoperative value.
      CONCLUSIONS: We found limited alterations of several OS parameters, which do not
      characterize either systemic or cellular high-grade OS during elective AAAR.

PMID- 14582544
TI  - Primary vascular access surgery in a well defined geographical region: long-term
      results of autogenous arteriovenous fistulas.
AB  - BACKGROUND AND AIMS: Autogenous fistula should be constructed in a minimum of 50%
      of all new ESRD patients scheduled for haemodialysis. The radio-cephalic fistula
      described by Brescia and colleagues in 1966 is considered to be the access of
      choice due to its good patency and low complication rate. The aim of this study
      was to evaluate the outcome of primary access surgery in a well-defined
      geographical region in Finland. MATERIAL AND METHODS: All primary vascular access
      procedures between 1990-1999 were selected in the local vascular registry.
      Additional data was collected from patients' case records. Kaplan-Meier method
      was used to calculate fistula patency. Multivariate analysis of four variables
      (age, gender, diabetes mellitus, smoking) was done to determine their association
      with primary success RESULTS: 407 primary procedures were done during the 10-year
      period including 405 (99.5%) autogenous fistulas and two prosthetic grafts
      (0.5%). 230 (56.8%) fistulas were used for haemodialysis during the study.
      Cumulative primary functional patency at one year was 84.1%, at two years 75.2%
      and at five years 50.1%. An attempt to salvage a failing or failed fistula was
      done in only 15 (6.5%) cases with insignificant impact on outcome. None of the
      tested variables was associated with poor functional success. CONCLUSIONS: The
      strategy of using native radio-cephalic fistula as a first access site results in
      excellent early and long-term functional patency for ESRD patient.

PMID- 14582545
TI  - Stability of internally fixed femoral neck fractures augmented with resorbable
      cement. A prospective randomized study using radiostereometry.
AB  - BACKGROUND AND AIMS: Internal fixation of displaced femoral neck fractures is
      associated with a high risk for complications such as non-union or avascular
      necrosis. A stable fracture fixation can improve prognosis although stability is
      often counteracted by weak osteoporotic bone. The aim with this study was to
      evaluate whether augmentation with resorbable calcium-phosphate cement could
      improve fracture stability during the early period after surgery as shown in
      biomechanical studies. MATERIAL AND METHODS: 40 ambulatory patients with a
      displaced femoral neck fracture were randomized to treatment with cannulated
      screws alone (controls) or screws combined with calcium-phosphate cement for
      augmentation (augmented). All patients were allowed unrestricted weight bearing
      after surgery. Fracture movement was measured with radiostereometry (RSA) at 1
      and 6 weeks. RESULTS: At 1 week the augmented fractures had moved on average 1.9
      +/- 1.0 mm while movement in the controls was 5.5 +/- 3.4 mm (p < 0.0001). The
      average total movement at 6 weeks was 6.9 +/- 2.9 mm and 10.9 +/- 5.1 mm,
      respectively (p < 0.005). Varus angulation and distal migration of the femoral
      head were the most common movements for both groups although augmented fractures
      had moved significantly less at both 1 and 6 weeks. There were no significant
      differences in angulation between groups around the longitudinal and transversal
      axes or in migration along the transverse or sagittal axes. CONCLUSION:
      Augmentation with calcium-phosphate cement improved the stability of internally
      fixed femoral neck fractures during the first six weeks after surgery, with
      improvement being less pronounced at six weeks compared with at one week.

PMID- 14582546
TI  - The epidemiology of multifocal upper limb fractures.
AB  - AIM: The aim of this study is to identify the epidemiology of multifocal upper
      limb fractures and define any commonly occurring patterns. PATIENTS: Patients
      included were those over the age of 13 years who presented to one orthopaedic
      trauma unit, in an eight-year period, and who sustained a multifocal upper limb
      fracture. RESULTS: There were 83 patients with 171 multifocal upper limb
      fractures. Mean age 60 years; range 13 to 92 years. 78 patients had bifocal
      fractures and 5 had trifocal. The most common pairing of fourteen different
      combinations was distal radius and proximal humerus. All but nine patients had
      involvement of the proximal humerus or distal radius. The most common injuries
      were the two-part proximal humerus fracture, the simple intra-articular olecranon
      fracture and the extra-articular fracture of the distal radius with metaphyseal
      comminution. CONCLUSION: This study has shown that multifocal fractures of the
      upper limb are most likely to occur in the middle aged to elderly women who have
      had a fall from standing height. As previously demonstrated osteopenic fractures
      are increasing in incidence in developed countries, where the population is
      ageing, which implies that the incidence of multifocal fractures of the upper
      limb is likely to increase.

PMID- 14582547
TI  - Gamma probe localization in the surgical treatment of osteoid osteoma.
AB  - BACKGROUND: Osteoid osteoma is a benign bone tumor typically inducing night pain.
      It has traditionally been treated with operative excision. An accurate
      localization and complete removal of the small lesion is difficult resulting in
      high recurrence rate and reoperations. AIMS: The purpose of the present study was
      to examine the applicability of a hand-held gamma probe in the intraoperative
      localization of an osteoid osteoma. MATERIAL AND METHODS: Five patients were
      examined and operated for osteoid osteoma. Dose of 740 MBq Technetium 99m was
      injected 3 hours before operation, and hand-held gamma probe was used for the
      intraoperative detection of the lesion. RESULTS: All patients were relieved their
      symptoms. A histologically confirmed, complete removal of the lesion was achieved
      in 4 of 5 patients. No recurrences has been seen in the follow-up of 6 years.
      CONCLUSIONS: The gamma probe is an useful tool in the surgical treatment of
      osteoid osteoma. The technique is rapid and simple resulting in more accurate
      excision of the small lesion.

PMID- 14582548
TI  - New bone formation induced by injection of native reindeer bone morphogenetic
      protein extract.
AB  - BACKGROUND AND AIMS: Bone morphogenetic proteins (BMPs) are usually administered
      with a solid framing material during open surgery. In some instances,
      percutaneous administration of injectable BMP would be preferable. We tested the
      new bone-forming activity of injectable native reindeer BMP extract in the Balb/C
      mouse thigh muscle pouch model. MATERIALS AND METHODS: The injectable implants
      contained 6 mg of native reindeer BMP extract and either physiological saline
      (NaCl/BMP) or collagen (Gel/BMP). Corresponding implants without BMP served as
      controls. New bone formation was evaluated based on incorporation of Ca45 and
      radiographically three weeks after the injection into the mouse thigh muscles.
      RESULTS: None of the injections without BMP were able to induce new bone visible
      in radiographs, whereas the injections with BMP induced new bone effectively.
      There were no significant differences in the area of new bone (p = 0.247) and its
      density (p = 0.739) between the NaCl/BMP and Gel/BMP groups. Ca-45 incorporation
      was multifold in the NaCl/BMP and Gel/BMP groups compared to the controls (p =
      0.000). No significant differences in Ca-45 incorporation (p = 0.739) between the
      NaCl/BMP and Gel/BMP groups were observed. CONCLUSION: Our results suggest that
      BMP can be administered percutaneously, and that collagen and physiological
      saline are equally good carriers of injectable implants of native reindeer BMP.

PMID- 14582549
TI  - Osteoporosis and the orthopaedic surgeon.
AB  - During the recent years, data regarding osteoporosis has accumulated and
      indicates that osteoporotic fractures in Scandinavia still increase. At the same
      time diagnostics and treatments have been improved. However, only a minority of
      patients with fractures and osteoporosis become identified. Surgeons and
      hospitals treating fractures should find means to detect patients who suffer from
      fractures due to osteoporosis, and establish programs for further evaluation and
      adequate treatment.

PMID- 14582550
TI  - Self-efficacy in relation to impairments and activities of daily living
      disability in elderly patients with stroke: a prospective investigation.
AB  - OBJECTIVES: The objectives of this prospective study, undertaken in elderly
      patients with stroke undergoing rehabilitation, were to determine to what extent
      fall-related self-efficacy changes over time, its relationships to objectively
      assessed functions and activities, and the predictive capacity of self-efficacy
      at discharge for activities of daily living 10 months after stroke. METHODS: The
      study comprised 37 patients, aged 66-89 years. Main outcome measurement
      instruments were the Falls Efficacy Scale (Swedish version), Berg Balance Scale
      and Functional Independence Measure. RESULTS: Significant improvements occurred
      in all these measures from admission to discharge, but patients with low self
      efficacy at discharge showed less pronounced improvements than those with high
      self-efficacy. Falls Efficacy Scale (Swedish version) was closely associated with
      all other measures and was a more powerful predictor of activities of daily
      living than the observer-based measures of balance. CONCLUSION: To minimize
      dependence in activities of daily living, rehabilitation interventions should
      incorporate self-efficacy enhancement.

PMID- 14582551
TI  - A causal model of rehabilitation resource use for subjects with spinal cord
      injury in Taiwan.
AB  - OBJECTIVE: The aim of this study was to construct an adequate causal model of
      rehabilitation resource use based on a Taiwanese rehabilitation database system.
      DESIGN: Cross-sectional analysis of data from a Taiwanese rehabilitation database
      system. SUBJECTS: Records from 68 patients (51 men, 17 women; mean age 43 years)
      with spinal cord injuries were used in the study. METHODS: Path analysis was used
      to identify a better-fitted model for patients with spinal cord injuries. RESULTS
      AND CONCLUSION: The results showed that the final causal model fits the data
      well. The findings also reveal that activities of daily living have the largest
      total effect on length of stay, whereas subjective well-being and gender have
      indirect effects on length of stay, mediating through activities of daily living
      and subjective well-being, respectively. The impact of subjective well-being on
      the length of stay in hospital for patients with spinal cord injuries deserves
      special attention, as the quality of life issue plays a vital role in
      rehabilitation of these patients. The influence of subjective well-being on
      activities of daily living suggests that therapy targeted at improving patients'
      subjective well-being is necessary. Additionally, the impact of sexual
      dysfunction of patients with spinal cord injuries should be investigated further.

PMID- 14582552
TI  - Development of a gait re-education system in incomplete spinal cord injury.
AB  - OBJECTIVE: The aim of the paper is to present the development of a system for
      swing phase restoration in patients with incomplete spinal cord injury. METHODS:
      The functional electrical stimulation based gait re-education system comprises a
      sensory system, a system providing cognitive feedback and a motor augmentation
      system facilitating and correcting the movement of the swinging extremity.
      Mathematical algorithms estimate swing quality and classify the swing phase of
      walking into 3 levels, termed cognitive feedback, which is provided to the
      patient as an auditory signal. A single-channel peroneal functional electrical
      stimulation was applied as a motor augmentation system to provide the patient
      with the motor assistance required. The important novelty of the proposed system
      is that motor assistance is provided only at the level that enables the patient
      to perform a good swing. RESULTS: The developed system was tested in a patient
      with incomplete spinal cord injury, with C4-5 lesion, whilst walking on a
      treadmill. The results show that the automated sensory-driven functional
      electrical stimulation augmentation system, providing only the minimal assistance
      required based on the subject's performance, is a viable approach that
      successfully releases a therapist from the task of delivering properly timed
      stimulation of adequate intensity in assisting the swing phase of walking.

PMID- 14582553
TI  - Functional independence in persons with spinal cord injury in Helsinki.
AB  - OBJECTIVE: To estimate the functional independence of persons with spinal cord
      injury according to the Functional Independence Measure motor items. DESIGN: The
      study design was cross-sectional. SUBJECTS: All adult citizens of Helsinki with
      traumatic spinal cord injury were identified. The final study group consisted of
      121/152 subjects (80%). METHODS: Functional Independence Measure assessments and
      American Spinal Cord Association examinations were performed on all subjects by
      the same experienced group including a physician and a physiotherapist. RESULTS:
      The most assistance-craving items were climbing stairs and bladder management.
      There were no significant differences between the genders. Subjects with
      tetraplegia needed significantly more assistance in all motor items except
      walking/wheelchair locomotion, where there was no significant difference.
      Subjects with tetraplegia in American Spinal Injury Association Impairment Scale
      D had higher Functional Independence Measure scores, more functional
      independence, than subjects in American Spinal Injury Association Impairment
      Scale A-C, the difference being significant. CONCLUSION: Because of new
      information, the results of this study may provide better possibilities for
      planning and coordinating rehabilitation measures and social services.

PMID- 14582554
TI  - Pulmonary function, working capacity and strength in young adults with Marfan
      syndrome.
AB  - OBJECTIVE: To investigate pulmonary function, working capacity and isokinetic
      muscle strength in subjects with Marfan syndrome. MATERIALS AND METHODS:
      Seventeen subjects, mean age 23 years, performed spirometry, maximal ergometer
      cycle tests and knee extension and flexion isokinetic torque tests. RESULTS: The
      subjects with Marfan syndrome had increased total and residual lung volume values
      compared with predicted values in healthy subjects and reduced peak oxygen uptake
      compared with healthy subjects of the same age. The isokinetic peak torque was
      reduced only at the highest velocity in the women. CONCLUSION: Thirteen subjects
      were able to perform the bicycle test until exhaustion without cardiovascular
      complications or pulmonary restrictions. However, their aerobic capacity was
      considerably decreased, which we suggest is caused by deconditioning. Further
      investigations are needed to reveal how pulmonary and cardiovascular limitations
      change with ageing and to give guidelines for exercise.

PMID- 14582555
TI  - Vertical posture and head stability in patients with chronic neck pain.
AB  - OBJECTIVE: To evaluate postural performance and head stabilization of patients
      with chronic neck pain. DESIGN: A single-blind comparative group study. SUBJECTS:
      Patients with work-related chronic neck pain (n = 9), with chronic whiplash
      associated disorders (n = 9) and healthy subjects (n = 16). METHODS: During quiet
      standing in different conditions (e.g. 1 and 2 feet standing, tandem standing,
      and open and closed eyes) the sway areas and the ability to maintain the postures
      were measured. The maximal peak-to-peak displacement of the centre of pressure
      and the head translation were analysed during predictable and unpredictable
      postural perturbations. RESULTS: Patients with chronic neck pain, in particular
      those with whiplash-associated disorders, showed larger sway areas and reduced
      ability to successfully execute more challenging balance tasks. They also
      displayed larger sway areas and reduced head stability during perturbations.
      CONCLUSION: The results show that disturbances of postural control in chronic
      neck pain are dependent on the aetiology, and that it is possible to quantify
      characteristic postural disturbances in different neck pain conditions. It is
      suggested that the dissimilarities in postural performance are a reflection of
      different degrees of disturbances of the proprioceptive input to the central
      nervous system and/or of the central processing of such input.

PMID- 14582556
TI  - Pain, trunk muscle strength, spine mobility and disability following lumbar disc
      surgery.
AB  - OBJECTIVE: To study associations between pain, trunk muscle strength, flexibility
      and disability in patients with lumbar disc herniation 2 months after surgery.
      DESIGN: Clinical cross-sectional survey. PARTICIPANTS: 172 operated lumbar disc
      herniation patients. METHODS: Back and leg pain on Visual Analogue Scale,
      Oswestry Disability Index and Brief Depression Scale were applied to assess the
      subjectively perceived outcome. Isometric and dynamic strength of trunk muscles
      and mobility of the lumbar spine were measured to mirror physical impairment.
      RESULTS: Two months after the operation median leg pain had decreased by 87% and
      back pain by 81%, respectively. However, moderate or severe leg pain was still
      reported by 25% and back pain by 20% of the patients. Approximately 30% of the
      patients perceived moderate or severe disability measured by the Oswestry index.
      Decreased muscle strength and spine mobility caused functional disability,
      especially in older patients and patients with postoperative pain. Furthermore,
      the ratio of trunk extension/flexion strength had changed in favour of the
      flexion muscles, being 0.98. Greater age and depression were associated with
      poorer postoperative recovery. CONCLUSION: Pain, decreased trunk muscle strength
      and decreased mobility still remained in a considerable proportion of patients
      with lumbar disc herniation 2 months after surgery. Early identification of those
      patients with restrictions is essential in order to commence rehabilitation.

PMID- 14582557
TI  - Cross-cultural adaptation of the Norwegian versions of the Roland-Morris
      Disability Questionnaire and the Oswestry Disability Index.
AB  - OBJECTIVE: To evaluate reliability and construct validity of the Norwegian
      versions of the Roland Morris Disability Questionnaire and the modified Oswestry
      Disability Index. DESIGN: Translation of two functional status questionnaires and
      a cross-sectional study of measurement properties. METHODS: The questionnaires
      were translated and back-translated following the Guillemin criteria. The
      Norwegian versions were tested for 55 patients with acute low back pain and 50
      patients with chronic low back pain. Test-retest with a 2-day interval was
      performed in a subsample of 28 patients from the chronic sample. Reliability was
      assessed by repeatability according to Bland and Altman, intraclass coefficient
      and coefficient of variation. Internal consistency was assessed by Cronbach's
      alpha. Concurrent construct validity was assessed with correlations between the
      questionnaires and the SF-36, Disability Rating Index and pain intensity.
      RESULTS: Repeatability of the Roland Morris Disability Questionnaire was 4
      points, coefficient of variation 15% and intraclass correlation coefficient 0.89,
      and of the modified Oswestry Disability Index 11, 12% and 0.88, respectively.
      Internal consistency was 0.94 for both questionnaires. The questionnaires
      correlated highly with the physical functioning scale of SF-36, moderately with
      pain, and low with mental scales of the SF-36. CONCLUSION: The reliability and
      construct validity of the Norwegian versions of the Roland Morris Disability
      Questionnaire and the modified Oswestry Disability Index are acceptable for
      assessing functional status of Norwegian-speaking patients with low back pain.

PMID- 14582558
TI  - The possible role of electromagnetic fields in bacterial communication.
AB  - This paper presents a general review of the current knowledge regarding bacterial
      communication via electromagnetic fields. The possible role of ultraviolet,
      visible and infrared light, extremely high frequency and low frequency
      electromagnetic fields as well as sound waves is discussed. The probable
      mechanisms of remote microbial interactions are raised. Future trends in the area
      of microbiology are also viewed.

PMID- 14582559
TI  - Severe acute respiratory syndrome in a medical center in Taipei.
AB  - From April 18 to May 31, 2003, 46 patients with probable severe acute respiratory
      syndrome were admitted to the negative-pressure isolation rooms of Mackay
      Memorial Hospital in Taipei, Taiwan. Their demographic, clinical, laboratory, and
      radiologic characteristics and clinical outcomes were analyzed. There were 15
      males and 31 females, in this cohort, 13 of whom were healthcare workers. The
      latter included 6 hospital staff and 7 medical personnel transferred from other
      hospitals. The most common symptoms were fever (100%, 46/46), cough (72%, 33/46),
      shortness of breath (46%, 21/46), and diarrhea (39%, 18/46). Other common
      findings were lymphopenia (57%, 26/46), thrombocytopenia (39%, 18/46), elevated
      lactate dehydrogenase (63%, 29/46), and elevated creatine kinase (24%, 11/46). A
      total of 7 patients (15%) required mechanical ventilation, and 8 (17%) died.
      Advanced age was an independent significant risk factor for death. Fever followed
      by rapidly progressive respiratory compromise led to significant morbidity and
      mortality in this cohort.

PMID- 14582560
TI  - Chlamydia pneumoniae IgG seropositivity and clinical history of ischemic heart
      disease in Singapore.
AB  - There is still substantial uncertainty concerning the association between
      Chlamydia pneumoniae and ischemic heart disease. This may partly be explained by
      the adjustment for potential confounders in different population studies. This is
      the first study in Singapore to look at the association of C. pneumoniae
      seropositivity with ischemic heart disease in a multivariate analysis. A random
      sample of 714 persons aged between 35 and 69 years was selected from the
      participants of the Singapore National Health Survey conducted in 1998. Data on
      clinical measurements and conditions were collected using biochemical tests and
      interviewer-based questionnaires. Ischemic heart disease was defined by the Rose
      questionnaire and included history suggestive of angina and/or myocardial
      infarction. Immunoglobulin G antibodies for C. pneumoniae were detected using an
      indirect microimmunofluorescence test, and seropositivity was defined as IgG
      titers > or = 1:16. There were no statistically significant differences in the
      prevalence rates of seropositivity to C. pneumoniae among the three ethnic
      groups, that is, Chinese (80.4%), Malays (74.0%), and Asian Indians (73.2%).
      There was no association between seropositivity and ischemic heart disease after
      adjustment for age alone (OR 1.00, 95% CI 0.54-1.83) or for age, sex, and other
      risk factors of atherosclerosis (OR 0.99, 95% CI 0.53-1.84). C. pneumoniae
      Immunoglobulin G seropositivity was not associated with an increased risk of
      ischemic heart disease as defined by the Rose angina questionnaire in Singapore.

PMID- 14582561
TI  - Rate of nasopharyngeal carriage, antimicrobial resistance and serotype of
      Streptococcus pneumoniae among children in northern Taiwan.
AB  - Multiple-antibiotic-resistant strains of Streptococcus pneumoniae are isolated
      from clinical specimens in Taiwan with increasing frequency. This study aimed to
      define the carriage rate of S. pneumoniae among children in northern Taiwan, and
      to determine the antibiotic susceptibility and the serotype incidence of these
      isolates. Nasopharyngeal swabs were taken from a total of 478 children (age, 1
      month-14 years) who sought medical care only for non-infectious disease or
      routine vaccination at our hospital between July 1998 and November 1999. S.
      pneumoniae was isolated from 95 patients, and the collected isolates were
      available for analysis. All pneumococcal isolates were serotyped and their
      antimicrobial susceptibility tested by standard methods. The total rate of
      pneumococcal carriage in the study population was 19.9% and the isolation rate
      was higher in children aged between 2 and 5 years. Only 10 (10.5%) of the
      isolates were susceptible to penicillin (minimum inhibitory concentration [MIC],
      < or = 0.06 microg/mL); 47 (49.5%) isolates were intermediately resistant (MIC,
      0.12-1 microg/mL) and 38 (40%) were highly resistant (MIC, > or = 2 microg/mL).
      Among the 95 S. pneumoniae isolates, the common serotypes were 23F (22%), 6B
      (18.9%), 19F (18.9%), and 14 (8.4%). Evaluation of the results showed that
      serotypes 23F (24.7%), 19F (21.2%), 6B (15.3%), and 14 (9.4%) composed 70.6% of
      all penicillin-non-susceptible S. pneumoniae isolates. The significant rate of
      isolation of penicillin-non-susceptible S. pneumoniae from children indicates
      that both the judicious use of antibiotics and the availability of conjugate
      pneumococcal vaccines are the most appropriate strategy to reduce the carriage of
      resistant pneumococci.

PMID- 14582562
TI  - Association of antibiotic utilization measures and reduced incidence of
      infections with extended-spectrum beta-lactamase-producing organisms.
AB  - With the overuse of expanded-spectrum cephalosporins, especially ceftazidime,
      outbreaks of extended-spectrum beta-lactamase (ESBL)-producing Klebsiella
      pneumoniae and Escherichia coli infections have been reported. In this
      prospective observational study, we demonstrated that the addition of
      piperacillin/tazobactam to the formulary and the restriction of ceftazidime were
      associated with a decrease in the percentage of ceftazidime-resistant isolates.
      When the use of ceftazidime decreased by 96.43%, and the use of
      piperacillin/tazobactam increased by over 50% during the 9-month study period, a
      concomitant decrease was found in the percentage of colonization and infection by
      ESBL-producing E. coli or K. pneumoniae in patients admitted to the intensive
      care unit. Results from this 9-month intervention study support the concept that
      levels of local and institutional use of ceftazidime are of substantial
      importance to the emergence and persistence of endemic ceftazidime-resistant K.
      pneumoniae.

PMID- 14582564
TI  - Outbreak of aseptic meningitis among adults in southern Taiwan.
AB  - A total of 38 adult cases of aseptic meningitis were diagnosed based on clinical
      manifestations as well as examination of cerebrospinal fluid at Kaohsiung
      Veterans General Hospital in 2001. The majority (31 cases, 82%) of cases occurred
      between June and August, and most (33 cases, 87%) of them aged from 18 to 35
      years (median age, 25 years). The male-to-female ratio was 2.16:1. Common
      clinical presentations included headache, fever, nausea or vomiting, and symptoms
      of common cold. On initial cerebrospinal fluid examination, white cell counts
      were above 500 cells/mm3 in 7 (18%) cases, and neutrophils predominated in 10
      (28%) of 36 cases. The cerebrospinal fluid protein concentration was below 100
      mg/dL in 29 (77%) of 38 cases, and hypoglycorrhachia (cerebrospinal fluid/serum
      glucose ratio <0.5) was seen in 9 (24%) cases. Enterovirus as a definite etiology
      was confirmed by isolation from cerebrospinal fluid in 17 (45%) of 38 cases and
      was the presumptive etiology by isolation from the stool or throat swab in 2 (5%)
      cases. Of the 19 cases with positive viral isolation, echovirus serotype 30
      accounted for the majority (15 cases, 79%), followed by echovirus serotype 6 (3
      cases, 16%), with one (5%) case undetermined. The viral isolation rate from
      cerebrospinal fluid correlated to the day of cerebrospinal fluid sampling after
      disease onset (chi2 = 12.05, p = 0.007). All patients were discharged
      uneventfully without receiving antibiotic therapy.

PMID- 14582563
TI  - Fluconazole resistance rate of Candida species from different regions and
      hospital types in Taiwan.
AB  - From April 15 to June 15, 1999, 581 clinical Candida isolates from 19 hospitals
      in Taiwan were collected and susceptibilities to fluconazole of these isolates
      were determined by a broth microdilution method. A total of 42 (7.2%) isolates
      were resistant to fluconazole. Isolates from medical centers had a higher
      resistance rate to fluconazole than those from regional hospitals (10.7% vs
      4.9%). Candida species isolated from different regions had different degrees of
      susceptibility to fluconazole. Approximately 2.5%, 6.5%, and 11.8% of Candida
      isolates from middle, north, and south regions, respectively, were resistant to
      fluconazole. The prevalence of the combination of Candida glabrata, Candida
      krusei, and Candida tropicalis infections were 44.5%, 49.8%, and 62.7% in middle,
      north, and south regions, respectively. There is an association between the rate
      of fluconazole resistance and the number of non-albicans Candida species
      collected from different regions and hospital types.

PMID- 14582565
TI  - Bacteremia in hematological and oncological children with febrile neutropenia:
      experience in a tertiary medical center in Taiwan.
AB  - A retrospective study of bacteremia in children with febrile neutropenia admitted
      to a medical center in Taiwan from January 1999 to December 1999 was performed.
      There were 190 episodes of febrile neutropenia during this period and 46
      pathogens were isolated from blood specimens in 38 bacteremic episodes (7 mixed
      infections). Pseudomonas aeruginosa (17.4%), Staphylococcus aureus (10.9%),
      Klebsiella pneumoniae (10.9%), and Enterobacter cloacae (10.9%) were the most
      common isolates. Three of the 5 isolates of S. aureus were resistant to
      methicillin. Twenty-three episodes of bacteremia (four mixed infections) were
      associated with recent antibiotic use. Of the 23 bacteremic episodes with recent
      antibiotic use, P. aeruginosa (20%), methicillin-resistant S. aureus (10%), K.
      pneumoniae (10%), Escherichia coli (10%), and E. cloacae (10%) were isolated most
      often. Relapsed leukemia (odds ratio 3, 95% confidence interval 1.4-6.5) and
      recent antibiotic therapy (odds ratio 3.4, 95% confidence interval 1.7-7.7) were
      the independent risk factors of bacteremia. There were 9 mortality cases in
      patients with bacteremia, including 4 cases with mixed infections, and 5 cases
      with P. aeruginosa, E. coli, Klebsiella oxytoca, S. aureus, and Streptococcus
      mitis, respectively. Broad-spectrum antibiotics were necessary in febrile
      neutropenic children because of the high percentage of mixed infection.

PMID- 14582566
TI  - Retrospective analysis of mortality and morbidity of pediatric systemic lupus
      erythematosus in the past two decades.
AB  - A total of 153 pediatric systemic lupus erythematosus patients (131 girls and 22
      boys) under 18 years of age who were newly diagnosed between 1980 and 2001 were
      retrospectively analyzed. All patients were followed up until death, loss of
      follow-up, or December 31, 2002. The mean follow-up duration was 6.11 +/- 9.02
      years. There were no differences in sex and family history between the 1980-to
      1990 cohort and the 1991-to-2001 cohort. The rate of complications of infection,
      skeletal manifestation, and end-stage renal disease were significantly higher in
      the 1980-to-1990 cohort (p=0.007, 0.001, and 0.000, respectively). Infection was
      the leading cause of death, and there were no differences in the cause of death
      between the 2 cohorts except end-stage renal disease (p=0.005). The survival rate
      was significantly worse in the 1980-to-1990 cohort than in the 1991-to-2001
      cohort (p=0.0012). The 2 significant poor prognostic factors were being female
      and the development of end-stage renal disease. We conclude that the mortality
      and morbidity of SLE has improved over the past 2 decades. It may be associated
      with newer treatment modalities and better supportive care available recently.

PMID- 14582567
TI  - Fatal bacteremic pneumonia caused by Aeromonas hydrophila in a previously healthy
      child.
AB  - Aeromonas hydrophila sepsis and pneumonia are rare diseases in children that
      carry a high mortality rate. We report a case of fatal bacteremic pneumonia
      caused by A. hydrophila in a previously healthy 5-year-old child. The source of
      infection was not determined and the child died within 4 hours of admission. In
      children who develop a fulminant disease of pneumonia with or without sepsis,
      particularly those who have underlying medical conditions, a possible A.
      hydrophila infection, though rare, should be considered. More reported cases are
      needed to establish the epidemiologic features of this disease in children.

PMID- 14582568
TI  - Systemic lupus erythematosus-related acute pancreatitis: a case report.
AB  - Systemic lupus erythematosus presenting as acute pancreatitis is rare. We report
      a case of a 12-year-old girl with a 1-year history of systemic lupus
      erythematosus who developed active pancreatitis. The pancreatitis was first
      manifested by nausea, vomiting, fever, and abdominal pain. Elevated serum amylase
      (578 U/L) and lipase levels (5588 U/L), and pancreatic enlargement on ultrasound
      and computerized tomography confirmed the diagnosis. She responded well to high
      dose corticosteroid. The high titer of antinuclear antibodies (1:1280) and low
      level of complement components (C3, 42.9 mg/dL; C4, 2.3 mg/dL) during the
      pancreatitis attack suggested that the pancreatitis may have been due to systemic
      lupus erythematosus exacerbation and not related to drug therapy.

PMID- 14582569
TI  - Hyper-IgM syndrome: a case report.
AB  - Hyperimmunoglobulin M syndrome is a rare primary immunodeficiency disorder. We
      report a case of a 6-month-old boy who suffered from developmental delays,
      frequent respiratory tract infection, and unusual fungal and bacterial infection.
      X-linked hyperimmunoglobulin M syndrome was ultimately diagnosed with decreasing
      immunoglobulin-G, A, and E (immunoglobulin G = 51.3 mg/dL, immunoglobulin A =
      8.32 mg/dL, immunoglobulin E <17.5 mg/dL), elevating immunoglobulin M
      (immunoglobulin M = 140 mg/dL), and decreasing T-cell expression of the CD40
      ligand over flow cytometry. Seizure episodes and hypotonia developed with greater
      signal intensity at the putamen in a brain magnetic resonance imaging, which is
      compatible with hypoxic ischemic encephalopathy. This is the youngest proven case
      of hyper-IgM syndrome in Taiwan ever reported.

PMID- 14582570
TI  - Temporal increase in the gastric colonization of Helicobacter pylori after
      healing of acetic acid-induced gastric ulcer in a miniature pig.
AB  - While the eradication of Helicobacter pylori has been reported to reduce the
      frequency of ulcer relapse, the preventative mechanism remains unknown. We
      investigated the changes in the level of gastric colonization 140 days after
      inducing gastric ulcer by acetic acid in the antral mucosa of a miniature pig
      infected with H. pylori. The gastric ulcer was induced endoscopically with 1 mL
      of 40% acetic acid 12 days after inoculation of H. pylori in a 3-month-old
      miniature pig. Gastric ulcer was healed by 30 days after ulcer induction and the
      levels of H. pylori in cardiac and antral mucosa increased gradually from 30 to
      71 days. The peak bacterial counts in the cardia and antrum were 6.1 and 6.6
      log10 cfu/g, respectively, or about 100-fold higher than the initial levels. The
      levels of H. pylori in cardiac and antral mucosa steadily decreased until
      reaching the initial levels at 127 days, while that in the fundic mucosa remained
      constant throughout the observation period. No ulcer recurrence was detected by
      endoscopy. These results suggested that the levels of H. pylori colonization
      increased temporally after healing of the acetic acid-induced gastric ulcer in
      the miniature pig.

PMID- 14582571
TI  - Physical and mental health problems associated with the use of alcohol and drugs.
AB  - The nature and extent of treated health problems in patients with problems
      related to the use of alcohol and drugs (including both licit and illicit drugs)
      were compared with the morbidity levels of all patients treated for all
      conditions in Canada. The morbidity experience of all patients with alcohol or
      drug (A/D) diagnoses treated as inpatients (n = 52,200 cases) in all Ontario
      hospitals in 1985-1986 (based on Hospital Medical Records Institute [HMRI] data)
      was compared with that of the total population of all inpatients treated in all
      Canadian hospitals using age-sex standardized morbidity ratios (SMR) and
      adjusting for multiple diagnoses. Of A/D cases, 32% were admitted with a primary
      A/D diagnosis and 68% with a secondary A/D diagnosis; 17% of A/D cases had
      multiple A/D diagnosis. On average, cases with a primary A/D diagnosis had 29%
      more diagnoses per case than all cases treated in Ontario. SMRs were highest for
      cases with diagnoses relating to the use or misuse of licit drugs (SMR = 13.32
      and 3.51 for those with primary and secondary drug diagnoses, respectively),
      intermediate for illicit drug cases (SMR = 8.87 vs. 4.74 for primary and
      secondary diagnoses, respectively), and lowest for patients with alcohol
      diagnoses (SMR = 6.68 and 4.12 for primary and secondary diagnoses,
      respectively). Excess morbidity for alcohol cases affected more diagnostic
      categories and body systems, being at a higher level than for drug cases. Alcohol
      or drug cases had particularly high SMRs for mental disorders, infectious and
      parasitic conditions, and injury and poisoning diagnoses. Alcohol or drug cases
      had reduced reproductive morbidity: for complications of pregnancy, childbirth,
      and the puerperium, SMR = 0.04 to 0.24 for cases with primary A/D diagnoses and
      SMR = 0.12 to 0.89 for those with secondary A/D diagnoses. Cases with drug
      diagnoses had a considerable reduction in SMR for certain conditions originating
      in the perinatal period: SMR = 0.0 for cases with primary drug diagnoses and SMR
      = 0.0 for secondary illicit drug diagnoses cases and SMR = 0.18 for secondary
      licit drug diagnoses cases.

PMID- 14582572
TI  - Correlates of illicit drug use in Karen villages in Northern Thailand.
AB  - A study was conducted in 31 Karen tribal villages in Northern Thailand in 1999
      2000 to address the question of why some villages have a relatively high
      prevalence of illicit drug use compared with others? Data were gathered from
      village leaders, residents, and through observations by field workers and the
      researchers, and included demographic, economic, and infrastructure development,
      and social and acculturation measures. Overall, few village-level variables were
      related significantly to drug use in the villages; those that were included: 1)
      better access to elementary education reported by "high drug" villages (81%) in
      comparison with "low drug" villages (29%) and 2) high drug villages reported
      having more alcoholic residents than low drug villages. The findings provide some
      support for the hypothesis that illicit drug use is positively associated with
      socioeconomic development, acculturation, and socialization into mainstream
      attitudes, values, and behaviors.

PMID- 14582574
TI  - Drug courts: current issues and future perspectives.
AB  - This article provides an overview of the evolution of the "drug court" concept in
      the United States, from its introduction in Miami in 1989 to the over 1300
      programs now operating or being planned in every state. The topics covered will
      include: a) a description of the drug court process and services compared with
      the traditional adjudication process; b) principal findings to date, including
      what has been learned and what still needs to be studied; c) implications of the
      drug court concept for other aspects of the U.S. justice system; and d)
      unresolved critical issues that will impact upon its future development.

PMID- 14582573
TI  - Adolescent's suicide attempts: populations at risk, vulnerability, and substance
      use.
AB  - Adolescence corresponds to a transition period that requires adaptation and
      change capacities and skills. Most young people succeed with this challenge,
      whereas a minority fail. In order to identify with the teenage culture, become
      autonomous, and differentiate from their parents, some adolescents choose to use
      drugs, beginning with the use of cigarettes, alcohol, cannabis, followed by other
      illicit drugs such as opiates and stimulants. A high proportion of these
      adolescents attempt suicide, which is the primary cause of death during
      adolescence in many European countries. Who are the "vulnerable" adolescents?
      What are the mechanisms that can explain the varieties of drug-use initiation or
      suicide attempts? Can "protective factors" be identified? What kind of strategies
      might be developed at a social and political level in order to prevent or to
      minimize drug abuse and suicide attempts, among other harmful behaviors? These
      issues will be discussed on the basis of the recent literature and in the light
      of a recent study carried out in the French-speaking part of Switzerland on large
      cohorts of adolescent drug users. Unresolved critical issues are noted and future
      needed research is suggested.

PMID- 14582575
TI  - Innovative approaches to identifying and responding to the needs of high risk
      youth.
AB  - Following a critical review of key issues facing the delivery of effective, cost
      attractive services to high-risk youth, and research addressing these
      experiences, we identify some innovative approaches to identify and respond to
      the multiple needs of these youth. The importance of providing family services
      with an ecological focus is stressed. Further, some exciting developments
      occurring in juvenile assessment centers. involving screening and in-depth
      assessment, as well as intervention strategies are presented. These innovative
      developments include for the Tampa Juvenile Assessment Center: 1) a family
      empowerment intervention service for arrested youth; 2) a family-focused early
      intervention, intensive case management service for youth entering a diversion
      program; and 3) for the Miami-Dade Juvenile Assessment Center, the comprehensive
      program of research and program development occurring in the context of the
      National Demonstration Project. We conclude with a discussion of major issues
      facing the field and the continuing need for a national commitment to help the
      many troubled youths entering the juvenile justice system.

PMID- 14582576
TI  - Lesbians' drinking patterns: beyond the data.
AB  - Early studies report very high rates of "alcohol abuse" and alcoholism among
      lesbians. However, serious methodological problems, including nonrepresentative
      samples that were often recruited in lesbian or gay lesbian bars, limit the
      validity of findings from these studies. In this article, I briefly review the
      literature on lesbians' use of alcohol and present findings from a recent study
      conducted in Chicago (USA). This study recruited a race- and age-diverse sample
      of lesbians and a demographically matched group of heterosexual women. Rates of
      "heavy" alcohol use and alcohol-use-related problems among lesbians were much
      lower in this study than in early studies. However, lesbians were more likely
      than their heterosexual counterparts to be in recovery and to have been in
      treatment for alcohol-use-related problems. Further, high rates of childhood
      sexual abuse, depression, and suicidal ideation reported by lesbians suggest that
      at least some groups may be at heightened risk for "heavy" drinking and drinking
      related problems. Nevertheless, results of this and other studies suggest that
      reports of heavy drinking and drinking-related problems among lesbians may have
      been inflated in earlier studies, or that heavy drinking and drinking-related
      problems may have declined among lesbians.

PMID- 14582577
TI  - Family-based interventions for substance use and misuse prevention.
AB  - Because "substance abuse" is a "family disease" of lifestyle, including both
      genetic and family environmental causes, effective family strengthening
      prevention programs should be included in all comprehensive substance abuse
      prevention activities. This article presents reviews of causal models of
      substance use and evidence-based practices. National searches by the authors
      suggest that there is sufficient research evidence to support broad dissemination
      of five highly effective family strengthening approaches (e.g., behavioral parent
      training, family skills training, in-home family support, brief family therapy,
      and family education). Additionally, family approaches have average effect sizes
      two to nine time larger than child-only prevention approaches. Comprehensive
      prevention programs combining both approaches produced much larger effect sizes.
      The Strengthening Families Program (SFP) is the only one of these programs that
      has been replicated with positive results by independent researchers with
      different cultural groups and with different ages of children. Few research-based
      programs have been adopted by practitioners, partly because of technology
      transfer issues. Overall, research on ways to improve dissemination, marketing,
      training, and funding is needed to improve adoption of effective prevention
      programs.

PMID- 14582578
TI  - Patterns of drug distribution: implications and issues.
AB  - This article delineates various patterns of illicit sales of drugs, especially at
      the retail (and near-retail) level, addressing a variety of central issues about
      drug sales and distribution documented during the past 30 years. including: a)
      the links between drug consumption and drug distribution activities; b) the
      various distribution roles; c) various levels of the distribution hierarchy; d)
      types of retail and wholesale markets; e) the association of drug distribution
      with nondrug associated criminality and violence. The article also will address
      the implications of drug distribution: whether various public policies such as
      supply reduction and source interdiction affect illicit drug markets, and how
      policing strategies and various law enforcement strategies can influence the
      involvement of individual participation in drug distribution activities. The
      overlooked contribution of treatment for "drug abuse" to reducing drug sales and
      distribution activities also will be considered as will other critical unresolved
      issues.

PMID- 14582579
TI  - Outcomes for substance user treatment in women: results from the Baltimore Drug
      and Alcohol Treatment Outcomes Study.
AB  - The Baltimore Drug and Alcohol Treatment Outcomes Study is a large study focusing
      on a single city. Over 1000 adult male and female substance users entering
      treatment in 16 publicly funded substance use treatment programs in the City of
      Baltimore between 1998 and 1999 were evaluated at four time periods (intake, 30
      days after treatment, 6 month, and 12 month follow-ups). A comprehensive
      psychological battery was administered at each assessment interval. In this
      article, we report on the seven domains (alcohol, drug, medical, legal,
      employment, family, and psychological) of the addiction severity index (ASI) with
      the 459 women who participated in the study. Overall, statistically significant
      differences across time showed improvement as a result of substance user
      treatment were found in six of the seven ASI domains; no statistically
      significant effects for time were found for the medical composite scores. Drug
      and alcohol use among the participants was significantly reduced as early as 30
      days after treatment. We discuss these findings in relation to the specific
      treatment needs of women who are addicted.

PMID- 14582580
TI  - Evaluation of drug use prevention programs directed at adolescents.
AB  - The aim of this article is to present a theoretical model of how to undertake
      evaluations of prevention programs directed at adolescents. Based on the results
      from metaanalyses of outcome studies of school-based programs, this article
      concludes that interactive programs tend to be more effective than not only those
      mainly intended to increase factual knowledge about tobacco, alcohol, and illegal
      drugs, but also those initiatives aimed at influencing adolescents' attitudes
      toward those substances. The interactive strategy corresponds to problem-based
      learning or the interactive educational approach, now widely popular in
      educational circles. These outcome studies have provided us with important
      knowledge. However, there are relatively few evaluation investigations that
      analyze in substantive detail the process by which adolescents change their
      alcohol, tobacco, and illegal drug-use behavior, and alter their perceptions
      about these substances. In an ongoing intervention study based on an interaction
      framework, involving all youngsters in the ninth grade (15-16 year olds, n = 300,
      undertaken in year 2001-2002) in the Aland Islands, Finland, the students'
      perceptions regarding the risks involved in illegal drug use could not be
      altered. Neither was it possible to decrease the alcohol or tobacco consumption
      during this school year. However, what did occur was that a number of
      expectations regarding alcohol were changed, which, in turn, might influence the
      patterns of alcohol use by the target group. The ways students in the Alands
      celebrate the end of junior high school are culturally embedded, and this may
      explain the lack of success in decreasing their alcohol consumption and tobacco
      use at the end of the ninth grade. Based on the analysis, a combination of
      outcome and process evaluations is recommended in order to reach a better
      understanding of how school prevention programs may achieve the desired goals.

PMID- 14582581
TI  - The role of work in substance dependency treatment: a preliminary overview.
AB  - This article describes four alternative models for the role of client work in
      substance dependency treatment. The most common model is Work as a Positive
      Outcome, which conceptualizes work (employment) as a desirable outcome of
      treatment. The Work Infusion Model conceptualizes work as a therapeutic factor in
      treatment. The Contingent Sanctions Model requires clients to work to avoid
      undesirable consequences, such as losing treatment. The Work as Reinforcement
      Model offers paid work as a reward for treatment adherence. This article
      discusses whether either standard substance dependency treatment or vocational
      services within treatment programs increase client employment, whether clients
      want to work, and whether sufficient services are available. The empirical
      support for each model of client work is summarized. Critical issues that must be
      addressed in this area are outlined.

PMID- 14582582
TI  - Drug use/misuse among health professionals.
AB  - Health professionals are among special populations in need of substance
      use/misuse prevention and treatment services. The behavior of impaired health
      professionals often have dire consequences to one's social, financial, and
      psychological life. This presentation will outline the epidemiology of substance
      use/misuse among health professionals, the consequences of the problem, and
      treatment issues. The work of Dr. Robert Coombs of the University of California,
      Los Angeles, School of Medicine and other United States and international
      scholars will be reviewed. Cross-national policies in this field will be
      highlighted. Unresolved critical issues will be noted and future needed research
      will be suggested.

PMID- 14582583
TI  - Alcohol misuse among elderly psychiatric patients: a pilot study.
AB  - The aim of this pilot study was to ascertain the frequency of alcohol misuse
      among the elderly (> 65) psychiatric referrals. Consecutive referrals to a
      suburban elderly psychiatric team were screened for alcohol misuse by using the
      CAGE questionnaire as a part of psychiatric assessment. Gamma-glutanyl
      transpeptidase (GGT) was measured in those showing evidence of alcohol misuse.
      Frequency of alcohol misuse in the elderly was found to be low. Alcohol misuse
      was associated with raised GGT, depression, being divorced/ widowed and living
      alone.

PMID- 14582584
TI  - Drug testing at work: issues and perspectives.
AB  - Over the past two decades there has been a significant rise in the number of
      employers requiring their staff or prospective staff members to undergo testing
      to determine whether they have been taking illicit drugs. Such testing usually
      takes place within the framework of broad employee-assistance programs and is
      underpinned by the wish to ensure public safety and corporate security, as well
      as achieving a "drug-free workplace" by helping staff who have drug-use-related
      problems. By whatever means these tests are conducted, though, issues of privacy
      raise a question mark against whether this is truly an area in which the
      interests of collective security should always override individual civil
      liberties.

PMID- 14582585
TI  - Effect of a triclosan-containing dental gel on the levels of prostaglandin I2 and
      interleukin-1beta in gingival crevicular fluid from adolescents with fixed
      orthodontic appliances.
AB  - The effect of a triclosan-containing (0.3%) dental gel on inflammatory mediators
      in gingival crevicular fluid (GCF) was evaluated in 14 healthy adolescents
      undergoing orthodontic treatment with fixed appliances. A double-blind randomized
      split-mouth study design was used with color-coded experimental and placebo gels.
      The gel was self-applied for 5 min twice daily for 14 days in custom-made soft
      plastic trays. Clinic al data (visible plaque index (VPI) and gingival bleeding
      index (GBI) and samples of GCF were collected at baseline and after 1, 2, 4, and
      6 weeks. The concentrations of prostaglandin I2 (PGI2) and interleukin-1beta (IL
      1beta were determined by radioimmuno- and enzyme-linked immunosorbent assays,
      respectively. No clinical effects of the gel applications regarding amount of
      plaque or gingival bleeding were unveiled. Neither the experimental nor the
      placebo gel applications caused any statistically significant alterations in the
      inflammatory mediators, PGI2 and IL-1beta, compared to baseline. In conclusion,
      the present study did not reveal any beneficial cffects of the triclosan
      containing gel regimen on mild gingivitis in adolescents with fixed orthodontic
      appliances.

PMID- 14582586
TI  - Variation in caries experience and sugar intake among secondary school students
      in urban and rural Uganda.
AB  - The objective was to assess the socio-demographic variation in caries experience
      and sugar intake among urban (Kampala) and rural (Lira) students in Uganda. In a
      cross-sectional survey, a total of 1146 adolescents aged between 13 and 19 years
      (response rate 87%) attending 10 secondary schools, 5 rural and 5 urban,
      completed questionnaires in respective schools. Clinical examination was
      conducted among 372 respondents (response rate 90%) from the main survey and
      dental caries was assessed. The results showed that a total of 80% of the
      students had DMFT >0. The corresponding rates in Kampala and Lira were 85% and
      76% (P < 0.05), respectively. The mean DMFT, DT, and MT for the sample were 2.9,
      2.5, and 0.5. Adjusted mean DMFT scores were 2.4 in Kampala and 3.3 in Lira (P <
      0.05). The mean frequency sugar score was 2.6 and sugar consumption was higher in
      females and in students of highly educated parents compared to their counterparts
      in the opposite groups. In conclusion, higher mean DMFT scores in urban than in
      rural areas are often reported from developing countries but this does not seem
      to apply to the Ugandan areas investigated. Kampala and Lira students were
      equally exposed to sweets and soft drinks but the differences in sugar
      consumption between students of higher and lower educated parents were most
      marked in Lira.

PMID- 14582587
TI  - Treatment of temporomandibular disorders among adolescents: a comparison between
      occlusal appliance, relaxation training, and brief information.
AB  - In a randomized trial the effects of occlusal appliance and relaxation therapy,
      each combined with brief information, were compared with brief information only,
      in adolescents with temporomandibular disorder (TMD) pain. One-hundred-and-twenty
      two adolescents (93 F and 29 M aged 12-18 years) were randomly assigned to one of
      the following 3 groups: brief information + occlusal appliance (BI + OA), brief
      information + relaxation therapy (BI + RT), or brief information (BI). Included
      were subjects reporting pain once a week or more often, in addition to receiving
      a diagnosis of TMD according to the Research Diagnostic Criteria (RDC/TMD). They
      were evaluated before and after treatment and at a 6-month follow-up by means of
      self-reports and clinical assessment. The result revealed a significantly higher
      reduction in frequency of pain, in pain intensity (visual analog scale [VAS]),
      and in a composite pain index (intensity x frequency) for patients treated with
      BI + OA compared with those treated with BI alone. In the BI + OA group, 60% of
      the patients attained a clinically significant improvement (at least 50% or more)
      on the pain index, a significantly higher proportion compared to that obtained in
      the other 2 treatment groups. Analgesic consumption was also significantly more
      reduced in the BI + OA group compared to the BI group. However, no significant
      differences were found between the treatment groups in jaw opening or in muscle
      and TMJ tenderness scores. Occlusal appliance was found to be superior to both
      relaxation therapy and brief information regarding pain reduction and can
      therefore be recommended when treating adolescents with TMD pain.

PMID- 14582588
TI  - Prevailing oral hygiene practices among urban Saudi Arabians in relation to age,
      gender and socio-economic background.
AB  - The aim was to analyze prevailing oral hygiene practices among urban Saudi
      Arabians in relation to age, gender, and socio-economic background. Structured
      interviews were performed with 1155 regular patients at two centers providing
      dental care for university and military staff and their families, respectively,
      in the city of Makkah. Consecutive patients were stratified according to gender
      and age into 6 age categories from 10 to 60 years, with 50 male or female
      subjects in each group at each center. Oral hygiene habits were correlated with
      the subject's age and gender, and analyzed statistically using a generalized
      linear model. It was found that 73% used a toothbrush daily, while a miswak was
      used daily by 65%. Significant differences were found between genders and age
      groups, and between the centers. Regular miswak use was more prevalent among men
      (P < 0.01), while women used toothbrush more than miswak (P < 0.05). Regular
      miswak use was more frequent at older age (P < 0.001) and tooth brushing was less
      prevalent. Forty-four percent of the 51- to 60-year-old patients at the military
      center never used a toothbrush. Regular toothbrush use was more prevalent in the
      youngest age groups (P < 0.001). Among the 10- to 15-year-olds, 45% at the
      university center used only a toothbrush, while no adolescents at the military
      center used only a toothbrush. We conclude that there are large differences in
      current oral hygiene habits among Saudi Arabians, and that these are related
      mainly to age and socio-economic level, and to a lesser extent gender. This
      should be taken into account when planning oral health strategies for different
      categories.

PMID- 14582590
TI  - Experimental autogenous tooth transplantation in the dog: a comparison between
      one- and two-stage surgical techniques.
AB  - Crucial if tooth transplantation is to succeed is preservation of the vitality of
      the cells of the periodontium and cementum of the tooth graft. Poor contact
      between the tissues of the recipient site and the root surface when teeth are
      transplanted to recipient sites prepared immediately prior to transplantation
      (one-stage technique) could, after transplantation, result in insufficient
      nutrition to the cells of the root surface and contribute to necrosis of the
      cells. To improve nutrition, tooth transplantation to recipient beds left to heal
      for 14 days was performed (two-stage technique). Clinical trials of tooth
      transplantation by the two-stage technique resulted in a low incidence of tooth
      graft loss and root resorption. The different results between these two methods,
      as well as difficulties in evaluating clinical trials, called for an experimental
      model to be established. In 5 beagle dogs, fully developed autogenous teeth were
      transplanted using both one-stage and two-stage surgical techniques. The control
      teeth were transplanted by the one-stage method to recipient beds prepared
      immediately before transplantation. The test teeth were transplanted using the
      two-stage method to recipient beds prepared and left to heal for 5 days prior to
      transplantation. Four pairs of teeth (1 test and 1 control) were transplanted in
      each dog. One pair of incisors and one pair of premolars were transplanted in the
      maxilla and in the mandible. Altogether 20 pairs of teeth were included in the
      study. One pair of teeth fractured during extraction and was therefore excluded
      from the study. Two pairs of teeth were lost in the first hours after
      transplantation. Evaluation of the remaining 17 pairs of teeth was made by
      routine histological examinations after a 6-month period of healing. The blinded
      examination failed to show a difference between the two surgical methods in terms
      of frequency of various types of root resorption. The differences between the
      results after long-term observation of human teeth transplanted by the one- and
      two-stage tooth transplantation techniques were not found by this experimental
      model.

PMID- 14582589
TI  - Temporomandibular joint related painless symptoms, orofacial pain, neck pain,
      headache, and psychosocial factors among non-patients.
AB  - The aims of this study were to assess the prevalence of temporomandibular joint
      related (TMJ) painless symptoms, orofacial pain, neck pain, and headache in a
      Finnish working population and to evaluate the association of the symptoms with
      psychosocial factors. A self-administered postal questionnaire concerning items
      on demographic background, employment details, perceived general state of health,
      medication, psychosocial status, and use of health-care services, was mailed to
      all employees with at least 5 years at their current job. The questionnaire was
      completed by 1339 subjects (75%). Frequent (often or continual) TMJ-related
      painless symptoms were found in 10%, orofacial pain in 7%, neck pain in 39%, and
      headache in 15% of subjects. Females reported all pain symptoms significantly
      more often than men (P < 0.001). Frequent pain and TMJ-related symptoms were
      significantly associated with self-reported stress, depression, and somatization
      (P < 0.001). Perceived poor general state of health (P < 0.001), health care
      visits (P < 0.001), overload at work (P < 0.001), life satisfaction (P < 0.05),
      and work satisfaction (P < 0.05) were also significantly associated with pain
      symptoms, but the work duty was not (P > 0.05). Our findings are in accordance
      with earlier studies and confirm the strong relationship between neck pain,
      headache, orofacial pain. TMJ-related painless symptoms, and psychosocial
      factors. Furthermore, TMJ-related symptoms and painful conditions seem to be more
      associated with work-related psychosocial factors than with type of work itself.

PMID- 14582591
TI  - Plasma levels of lidocaine, o-toluidine, and prilocaine after application of 8.5
      g Oraqix in patients with generalized periodontitis: effect on blood
      methemoglobin and tolerability.
AB  - Oraqix, a novel non-injectable anesthetic gel containing lidocaine and prilocaine
      and a thermosetting agent has been developed to provide localized anesthesia in
      periodontal pockets during scaling/root planing (SRP). The aim of this open study
      was to determine the plasma levels of lidocaine and prilocaine following
      application of 8.5 g Oraqix (5 cartridges) to 11 patients with generalized
      periodontitis (> or = 49% of tooth pockets > or = 5 mm and > or = 23% of pockets
      > or = 6 mm). Oraqix was applied to the pockets during periodontal probing and
      SRP over a 2.6 3.4 h period. Blood samples were collected up to 10 h after the
      start of application of Oraqix. Peak plasma levels of lidocaine (0.16-0.55 mg/L)
      and prilocaine (0.05-0.18 mg/L) occurred 2.0-3.7 h and 2.0-3.3 h, respectively,
      after the start of application of Oraqix. These levels are well below threshold
      levels for initial signs of central nervous system (CNS) toxicity. In conclusion,
      application of 8.5 g Oraqix (212.5 mg of lidocaine base and 212.5 mg of
      prilocaine base) in periodontal pockets was well tolerated and displayed a wide
      safety margin with respect to plasma levels normally associated with systemic
      toxicity.

PMID- 14582592
TI  - A two-year clinical evaluation of a new calcium aluminate cement in Class II
      cavities.
AB  - A calcium aluminate cement (Doxa Certex, Uppsala, Sweden) has recently been
      developed intended for use as direct restorative filling material for posterior
      restorations. The material is inorganic and non-metallic and the main components
      are CaO, Al2O3, SiO2, and water. The aim of this study was to evaluate intra
      individually the experimental calcium aluminate cement (CAC) and a resin
      composite (RC) in Class II restorations. Each of 57 participants received at
      least one pair of restorations of the same size, one CAC and one RC (Tetric
      Ceram). Sixty-one pairs were performed. The restorations were evaluated
      clinically, according to slightly modified USPHS criteria, at baseline, after 6
      months, 1, and 2 years. One-hundred-and-twenty restorations were evaluated at 2
      years. Postoperative sensitivity was reported for 5 restorations (2 RC, 3 CAC).
      Significantly better clinical durability was shown for RC. Five non-acceptable
      CAC restorations (8.2%) were observed at 6 months, 10 CAC (16.7%) and 2 RC (3.3%)
      at 12 months, and 11 CAC (18.3%) at 24 months. This resulted in a cumulative
      failure frequency of 43.3% for the CAC material and 3.3% for the RC material.
      Main reasons for failure for the CAC were partial material fracture (7), cusp
      fracture (5), and proximal chip fracture (6). The CAC showed a non-acceptable
      clinical failure rate for Class II restorations, probably caused by its difficult
      handling and low mechanical properties.

PMID- 14582593
TI  - Antimicrobial effects of glass ionomer cements containing bioactive glass (S53P4)
      on oral micro-organisms in vitro.
AB  - The antimicrobial effects of two glass-ionomer cements (GICs), GC Fuji II and
      Fuji II LC, mixed with different amounts (0 wt%, 10 wt% and 30 wt% of the total
      powder weight) of bioactive glass (BAG), S53P4, on Streptococcus mutans and
      Candida albicans were studied in vitro. The growth inhibition was tested using
      agar diffusion. The materials were also studied in a liquid media. The effect of
      the material extracts on acid production was studied using cell suspensions. The
      antimicrobial activity of the materials was examined by incubating the cell
      suspensions with the material powder. In the agar diffusion test, only the GICs
      containing 30 wt% BAG inhibited the growth of S. mutans. When the materials were
      tested in culture medium, no inhibitory effects on S. mutans were detected. The
      only materials to inhibit acid production of S. mutans were the GIC extracts
      without added BAG. Furthermore, they also had antibacterial activity against S.
      mutans when tested as powders. We found very few effects of the tested materials
      on C. albicans. The only material with an antimicrobial effect on C. albicans was
      BAG when incubated in a suspension with C. albicans. This is the first time that
      this effect has been demonstrated for C. albicans. By adding BAG to GICs the
      structure of the material becomes more brittle than the structure of GICs without
      BAG. Thus, in addition to the composition of the tested materials, their
      structure may also have influenced the results. In summary, commercially
      available GICs and GIC disks containing 30 wt% of BAG exerted antibacterial
      effects on S. mutans. BAG exerted antimicrobial effects on both S. mutans and C.
      albicans.

PMID- 14582594
TI  - A four to six years follow-up of indirect resin composite inlays/onlays.
AB  - The objective of this clinical survival study was to evaluate the performance of
      indirect resin composite inlays and onlays. Patients were recruited among the
      dental school clientele needing posterior approximal restorations and preferring
      esthetic restorations. Two clinical teachers and 6 trained students under
      supervision carried out the preparations, made impressions, and prepared stone
      casts. Inlays/onlays from Tetric, Z100, or Maxxim were light-cured and
      transferred to a light oven for secondary curing. At the 4 6 year recall, the
      inlays/onlays were evaluated using slightly modified US Public Health Service
      criteria, bitewing radiographs, and plastic dies based on replica impressions.
      All 25 treated patients with a total of 64 inlays/onlays presented for the
      assessment. The right-censored observation periods ranged from 48 to 75 months,
      with a mean of 59. With the exception of three failed inlays/onlays scored as 'D'
      (2 fractures, 1 caries), i.e. 5%, the majority were classified as successful.
      This was based on 43 'A' (optimal) and 18 'B' (acceptable) ratings, each of which
      represented the lowest rating for each individual restoration. The major reason
      for 'B' ratings was imperfect anatomical form, mostly absence of proximal
      contacts. The present clinical trial demonstrated that inlays/onlays made from
      Tetric, Z100, and Maxxim performed equally well over the 5-year period. Within
      the limits of this study it is concluded that the resin composite inlay/onlay
      technique should be considered as an alternative to direct fillings in the
      approximal posterior region.

PMID- 14582595
TI  - Restorative treatment and use of local anesthesia in free and subsidized public
      dental services in Helsinki, Finland.
AB  - Our aim was to evaluate restorative treatment and the use of local anesthetics in
      free and subsidized public dental care in Helsinki, Finland. Public dental
      clinics are open to all patients under the age of 36, and to some specific groups
      above that age. Patients up to age 19 receive all treatment free of charge and
      others at highly subsidized rates. Data were collected in May 2001 during a
      maximum 2-week period covering all public dental clinics in Helsinki. A one-page
      questionnaire was sent to all dentists (n = 140) in clinical fields. The data
      requested included the patient's gender and year of birth, and details on
      restorations: which tooth and which surfaces were filled, the reason for
      placement or replacement, the material used, and use of local anesthetic. The
      response rate was 96%. Of all restorations (n = 3057) placed, 14% were in primary
      teeth and in permanent teeth: 17% in premolars, 17% in incisors, and 52% in
      molars; the restorative material most often used was composite resin (69%). Glass
      ionomer/compomers dominated in the primary teeth. Local anesthetic was used least
      (35%) in patients under 13 years of age. Replacements of restorations accounted
      for 10% of all in the free service (under 20 years of age) and 46% in subsidized
      dental care (20 and older). The major reasons for replacement were secondary
      caries (41%) and fractured or lost restoration (40%).

PMID- 14582596
TI  - Work site health promotion research: to what extent can we generalize the results
      and what is needed to translate research to practice?
AB  - Information on external validity of work site health promotion research is
      essential to translate research findings to practice. The authors provide a
      literature review of work site health behavior interventions. Using the RE-AIM
      framework, they summarize characteristics and results of these studies to
      document reporting of intervention reach, adoption, implementation, and
      maintenance. The authors reviewed a total of 24 publications from 11 leading
      health behavior journals. They found that participation rates among eligible
      employees were reported in 87.5% of studies; only 25% of studies reported on
      intervention adoption. Data on characteristics of participants versus
      nonparticipants were reported in fewer than 10% of studies. Implementation data
      were reported in 12.5% of the studies. Only 8% of studies reported any type of
      maintenance data. Stronger emphasis is needed on representativeness of employees,
      work site settings studied, and longer term results. Examples of how this can be
      done are provided.

PMID- 14582597
TI  - Technical assistance for the evaluation of community-based HIV prevention
      programs.
AB  - Funding agencies are using technical assistance (TA) to strengthen the evaluation
      capacity of community-based organizations (CBOs) engaged in HIV prevention
      efforts. The authors used qualitative methods to identify the types of evaluation
      TA needed by CBOs, to understand CBOs' past experiences with evaluation TA, and
      to elicit ideas for optimal delivery of evaluation TA. Assistance in developing
      evaluation tools and data analysis were the most commonly cited needs. Preferred
      TA providers were characterized as having practical expertise, accessibility,
      cultural competence, communication skills, and collaboration skills. Critical
      elements of an ideal TA system were adequate funding, program-specific TA, and
      extensive interaction between TA providers and CBO staff. Study data were used to
      generate a set of recommendations for health educators and others who may provide
      CBOs with TA for evaluating prevention programs.

PMID- 14582598
TI  - The life history interview method: applications to intervention development.
AB  - There is an urgent need to develop and test health promotion strategies that both
      address health disparities and elucidate the full impact of social, cultural,
      economic, institutional, and political elements on people's lives. Qualitative
      research methods, such as life history interviewing, are well suited to exploring
      these factors. Qualitative methods are also helpful for preparing field staff to
      implement a social contextual approach to health promotion. This article reports
      results and application of findings of life history interviews conducted as part
      of intervention planning for the Harvard Cancer Prevention Program Project,
      "Cancer Prevention in Working-Class, Multi-Ethnic Populations." The salient
      themes that emerged from interviews with a multi-ethnic, purposive sample are
      centered on six construct domains: immigration and social status, social support,
      stress, food, physical activity, and occupational health. Insights gained from
      thematic analysis of the interviews were integrated throughout intervention and
      materials development processes.

PMID- 14582599
TI  - Assessing organizational capacity to deliver HIV prevention services
      collaboratively: tales from the field.
AB  - Collaborative efforts between university researchers and community entities such
      as citizen coalitions and community-based organizations to provide health
      prevention programs are widespread. The authors describe their attempt to develop
      and implement a method for assessing whether community organizations had the
      organizational capacity to collaborate in a national study to prevent HIV
      infection among young men who have sex with men and what, if any, needs these
      institutions had for organizational capacity development assistance. The
      Feasibility, Evaluation Ability, and Sustainability Assessment (FEASA) combines
      qualitative methods for collecting data (interviews, organizational records,
      observations) from multiple sources to document an organization's capacity to
      provide HIV prevention services and its capacity-development needs. The authors
      describe experiences piloting FEASA in 13 communities and the benefits of using a
      systematic approach to partnership development.

PMID- 14582600
TI  - Evaluation of an HIV and STD prevention program for adolescents in juvenile
      rehabilitation centers.
AB  - The aim of this study was to evaluate a sexual and STD/AIDS prevention program
      tailored for adolescents with social adaptation difficulties in juvenile
      rehabilitation facilities. The impact of the intervention on the psychosocial
      determinants of condom use were assessed, using a pre-test post-test quasi
      experimental design. A total of 296 adolescents participated in the program
      (experimental group) while 240 adolescents did not receive the intervention
      (control group). The program led to positive outcomes among participants with
      respect to several of the main psychosocial determinants of condom use for sexual
      intercourse with a new partner. The results suggest that interventions that draw
      upon a combination of theoretical knowledge and consideration of the specific
      characteristics of the milieu could be efficient in promoting safer sexual
      practices among adolescents in juvenile rehabilitation centers.

PMID- 14582601
TI  - Availability, accessibility, and preferences for fruit, 100% fruit juice, and
      vegetables influence children's dietary behavior.
AB  - The relationships among home fruit (F), 100% fruitjuice (J), and vegetable (V)
      availability and accessibility separately, as reported by 225 fourth- through
      sixth-grade children and their parents (n = 88), separately, and FJV preferences
      to child-reported FJV consumption were assessed. For girls, child-reported FJV
      availability and accessibility accounted for 35% of the variability in FJV
      consumption. Child-reported availability and parent-reported accessibility were
      significantly correlated with child FJV consumption in a combined model. For
      children with high FJV preferences, FJV availability was the only significant
      predictor, whereas both availability and accessibility were significantly related
      to consumption for children with low FJV preferences. Interventions targeting
      child dietary behaviors may need to tailor to the home environment, separately by
      gender. Extra efforts are necessary by parents to enhance accessibility among
      children who do not like FJV.

PMID- 14582602
TI  - Laboratory markers and germ cell tumors.
AB  - The International Germ Cell Consensus Classification (IGCCC) of testicular germ
      cell tumors (TGCT) in 1997 included three serum tumor markers, serum lactate
      dehydrogenase catalytic concentration (S-LD), serum alpha fetoprotein
      concentration (S-AFP), and serum human chorionic gonadotropin concentration (S
      hCG). The recommendation should be implemented for all patients with TGCT and is
      also useful for patients with ovarian and extragonadal germ cell tumors. A fourth
      serum tumor marker for TGCT, S-LD isoenzyme 1 (S-LD-1), is also relevant for
      TGCT. Patients with seminoma have a raised S-LD-1 more often than a raised S-AFP
      and S-hCG, whereas patients with nonseminoma have a raised S-AFP more often than
      a raised S-LD-1 and S-hCG. A new model combining IGCCC and S-LD-1 predicts
      survival better than previous staging systems. LD-1 is related to a
      characteristic chromosomal abnormality in all types of TGCT, a high copy number
      of chromosome 12p. In contrast, AFP and hCG are found mainly in nonseminomatous
      germ cell tumors and they related to the histologic differentiation of the
      tumors. The different biologic background for the serum tumor markers may
      contribute to the difference in their clinical behavior.

PMID- 14582603
TI  - Nonepithelial tumors and tumor-like lesions of the prostate gland.
AB  - Many significant benign and malignant nonepithelial tumors and stromal tumor-like
      lesions arise in the prostate gland. Although such lesions are rare, their
      recognition by the pathologist is essential because their treatment and prognosis
      are quite variable. In this review, lesions of the specialized prostatic stroma,
      that is, lesions that can be seen in the stroma of the prostate but not in that
      of other organs, except for the phyllodes type of lesions, are discussed. Benign
      and malignant lesions of the soft tissues that occur in the stroma of other
      organs and are seen with some frequency in the prostate are also discussed. Few
      of the rarer soft tissue lesions are mentioned. Lesions and tumors with
      melanocytic differentiation, hematopoietic derivation, and germ cell tumors are
      described. It is hoped that this review will serve as a useful reference when
      encountering some of these lesions, all of which are referenced to their original
      and subsequent reports. Some non-English language references are also cited to
      reflect the international recognition of these lesions or to give credit to the
      author who first described the entity.

PMID- 14582604
TI  - Carrier testing for autosomal-recessive disorders.
AB  - The aim of carrier testing is to identify carrier couples at risk of having
      offspring with a serious genetic (autosomal recessive) disorder. Carrier couples
      are offered genetic consultation where their reproductive options, including
      prenatal diagnosis, are explained. The Ashkenazi Jewish population is at
      increased risk for several recessively inherited disorders (Tay-Sachs disease,
      Cystic fibrosis, Canavan disease, Gaucher disease, Familial Dysautonomia, Niemann
      Pick disease, Fanconi anemia, and Bloom syndrome). Unlike Tay-Sachs disease,
      there is no simple biochemical or enzymatic test to detect carriers for these
      other disorders. However, with the rapid identification of disease-causing genes
      in recent years, DNA-based assays are increasingly available for carrier
      detection. Approximately 5% of the world's population carries a mutation
      affecting the globin chains of the hemoglobin molecule. Among the most common of
      these disorders are the thalassemias. The global birth rate of affected infants
      is at least 2 per 1000 (in unscreened populations), with the greatest incidence
      in Southeast Asian, Indian, Mediterranean, and Middle Eastern ethnic groups.
      Carriers are detected by evaluation of red cell indices and morphology, followed
      by more sophisticated hematological testing and molecular analyses. The following
      issues need to be considered in the development of a carrier screening program:
      (1) test selection based on disease severity and test accuracy; (2) funding for
      testing and genetic counselling; (3) definition of the target population to be
      screened; (4) development of a public and professional education program; (5)
      informed consent for screening; and (6) awareness of community needs.

PMID- 14582605
TI  - Bioreactors for cardiovascular cell and tissue growth: a review.
AB  - Heart disease is a major cause of death in the Western world. In the past three
      decades there has been a number of improvements in artificial devices and
      surgical techniques for cardiovascular disease; however, there is still a need
      for novel devices, especially for those individuals who cannot receive
      conventional therapy. The major disadvantage of current artificial devices lies
      in the fact that they cannot grow, remodel, or repair in vivo. Tissue engineering
      offers the possibility of developing a biological substitute material in vitro
      with the inherent mechanical, chemical, biological, and morphological properties
      required in vivo, on an individual patient basis. In order to develop a true
      biological cardiovascular device a dynamic physiological environment needs to be
      created. One approach that employs the use of a simulated biological environment
      is a bioreactor in which the in vivo biomechanical and biochemical conditions are
      created in vitro for functional tissue development. A review of the current state
      of the art bioreactors for the generation of tissue engineered cardiovascular
      devices is presented in this study. The effect of the simulated physiological
      environment of the bioreactor on tissue development is examined with respect to
      the materials properties of vascular grafts, heart valves, and cardiac muscles
      developed in these bioreactors.

PMID- 14582606
TI  - Impulsive-motion model for computing the closing motion of mechanical heart-valve
      leaflets.
AB  - The speed of mechanical heart-valve leaflets is known to be an important quantity
      for predicting cavitation, yet no simple computational means exists for
      predicting the leaflet speed. In this study, a model for simulating the motion of
      heart-valve leaflets in rigid test systems is presented. The input for the
      simulations is the ventricular pressure trace, readily measured in heart-valve
      tests. The model is based upon an impulsive-motion approximation, wherein the
      motion within the system is produced by rapid acceleration at the boundary, e.g.,
      by a moving piston. A set of quasisteady, linear equations for the pressure field
      that are decoupled from the leaflet equation of motion is derived. The pressure
      field and leaflet moment are computed without the need to treat moving
      boundaries. Model predictions of closing time compared favorably with those
      measured in a 1994 cavitation study. Computed values of leaflet tip speed were
      also compared with those of a previous study, at the same value of average
      pressure slope. The model values were in agreement with measured speeds, given
      the limitations of using the average pressure slope as a metric for comparison.

PMID- 14582607
TI  - Finite element model of mechanically induced collagen fiber synthesis and
      degradation in the aortic valve.
AB  - Tissue-engineered trileaflet aortic valves are a promising alternative to current
      valve replacements. However, the mechanical properties of these valves are
      insufficient for implantation at the aortic position. To simulate the effect of
      collagen remodeling on the mechanical properties of the aortic valve, a finite
      element model is presented. In this study collagen remodeling is assumed to be
      the net result of collagen synthesis and degradation. A limited number of fibers
      with low initial fiber volume fraction is defined, and depending on the loading
      condition, the fibers are either synthesized or degraded. The synthesis and
      degradation of collagen fibers are both assumed to be functions of individual
      fiber stretch and fiber volume fraction. Simulations are performed for closed
      aortic valve configurations and the open aortic valve configuration. The
      predicted fiber directions for the closed configurations are close to the fiber
      directions as measured in the native aortic valve. The model predicts the
      evolution in collagen fiber content and the effect of remodeling on the
      mechanical properties.

PMID- 14582609
TI  - Use of cardiac electric near-field measurements to determine activation times.
AB  - In a recent paper, we described the behavior of the cardiac electric near-field,
      E, parallel to the tissue surface during continuous conduction. We found that
      T(E), the time at which the peak near-field, E, occurs, is an accurate marker of
      local activation time. Examination of experimentally recorded E vector loops
      revealed a large variety of morphologies. We postulated that propagation around
      an obstacle could lead to the observed deviations in loop morphology. The purpose
      of this study was to determine if this was plausible, and if so, whether T(E)
      remains an accurate time marker of local activation under these conditions. We
      used a monodomain computer model of a sheet of cardiac tissue with a central
      conduction obstacle immersed in an unbounded volume conductor. Activation times
      T(Im), T(phi), and T(E) were derived from the transmembrane current I(m), the
      extracellular potential phi(e), and E, respectively. The obstacle led to
      deformations of the vector loops, morphologically similar to those observed
      experimentally, particularly during the initial and terminal phases, and to a
      lesser degree near the time of E. Despite these loop deformations, T(E) was an
      accurate time marker of local activation. We found that T(E) was significantly
      closer to T(Im) than T(phi). We concluded that isochrone maps computed from T(E)
      better reflect intracellular activation patterns than those computed from T(phi).
      For a given electrode spacing of 60 microm, the sensitivity to noise of E was
      significantly less than that of phi(e). Hence, T(E) was less affected by noise
      than T(phi).

PMID- 14582608
TI  - Path-dependent hemodynamics of the stenosed carotid bifurcation.
AB  - Previous work using computational simulations and experimental flow
      visualizations has demonstrated marked differences in local flow patterns between
      stenosed carotid bifurcation models having the same stenosis severity but
      different stenosis geometries. Since local blood flow patterns are known to
      influence thrombosis and atherosclerotic plaque development and rupture, such
      differences may in turn reflect differences in thromboembolic and atherosclerotic
      potential, and hence risk of ischemic stroke. Towards testing this hypothesis, we
      tracked point particles, representing uniformly distributed blood elements,
      through concentrically and eccentrically stenosed carotid bifurcation models, and
      computed and compared various path-dependent hemodynamic parameters between the
      models. Our results suggest that residence time alone is not sensitive to
      stenosis geometry; however, notable differences between the stenosis models were
      observed with residence time indicators that incorporate shear-related phenomena,
      such as the transit times and levels of activation of platelets that exceed a
      given shear threshold. Specifically, these and other indicators, including the
      magnitude of platelet shear exposure and the size and density of local platelet
      and monocyte deposition, were found to be higher in the eccentric model.
      Experimental work is now required to assess the significance of these
      differences.

PMID- 14582610
TI  - Characteristics of blood flow resistance under transverse vibration: red blood
      cell suspension in Dextran-40.
AB  - Vibration under shear flow causes the reduction of flow resistance for shear
      thinning fluids. The present study investigates the effect of vibration on the
      flow resistance of a nonaggregating red blood cell (RBC) suspension with a newly
      designed pressure-scanning capillary viscometer (PSCV). The PSCV was originally
      designed to measure non-Newtonian viscosity continuously over a range of shear
      rates at a time, which was slightly modified and used for the present study. Low
      frequency vibration was applied perpendicular to the direction of the flow. The
      effect of the transverse vibration was investigated for both Newtonian fluids and
      nonaggregating RBC suspensions. The experimental results showed that the
      vibration had no effect on the flow resistance of the Newtonian fluids. However,
      the vibration caused a reduction of the flow resistance of the RBC suspension.
      The reduction of the flow resistance was strongly dependent on both frequency and
      amplitude of vibration.

PMID- 14582611
TI  - Oxygen tension imaging in the mouse retina.
AB  - A newly developed microscope-based imaging system was used to measure the oxygen
      tension (PO2) inside the retinal and choroidal vessels of mice and to generate in
      vivo maps of retinal PO2. These maps were generated from the phosphorescence
      lifetimes of an injected palladium-porphyrin compound using a frequency-domain
      measurement. The system was fully calibrated and used to produce retinal PO2 maps
      at different inspiratory oxygen fractions. PO2 rose accordingly and predictably
      as inspiratory O2 was stepped from hypoxic to hyperoxic conditions. Important
      experimental and acquisition parameters necessary for applying phosphorescence
      lifetime imaging to the mouse eye were investigated, including camera exposure
      and intensifier gain settings. Because of a need to limit light exposure to the
      retina, PO2 map quality as measured by the coefficient of determination was
      investigated as a function of signal-to-noise and accumulated excitation energy
      deposition. With the development of this technology for use in mice, the
      potential for investigating the oxygen dynamics in genetically engineered mouse
      models of retinal disease, including diabetic retinopathy, glaucoma, and age
      related macular degeneration, is advanced.

PMID- 14582612
TI  - Nonlinear coupling among heart rate, blood pressure, and respiration in patients
      susceptible to neuromediated syncope.
AB  - The aim of this study is to evaluate the degree of coupling between the
      cardiovascular variability series and the respiration in subjects susceptible to
      neurally mediated syncope. Twenty-one informed patients susceptible to syncope
      and ten sex- and age-matched control subjects were enrolled in the study. ECG,
      respiration activity, and arterial blood pressure were simultaneously recorded at
      rest (controlled and free breathing) and during the 70 degrees head-up TILT test
      (free breathing). The degree of nonlinear coupling among heart rate variability
      (HRV), blood pressure variability (BPV), and respiration was quantified by means
      of two indices according to a multivariate embedding-based approach. Eleven
      patients developed syncope during the TILT test. We found that during the late
      TILT phase, the TILT-positive group experienced a significant increase in
      nonlinear coupling respect to the mid TILT phase (p < 0.01, Wilcoxon
      nonparametric test for pair data) while the TILT-negative group did not (p <
      0.01, Mann-Whitney U-test). If the proposed nonlinear coupling indexes can be
      considered expression of the coupling mechanisms involved in the vagal regulation
      of the cardiovascular system, an increase in vagal tone accompanied by a decrease
      in sympathetic activity seem to occur before a vasovagal event.

PMID- 14582614
TI  - Biomechanical strategies for articular cartilage regeneration.
AB  - Two major contributions to the development of articular cartilage are growth
      factors and mechanical loading. Growth factors have long been used to modulate
      the secretion of certain molecules from different cells. The TGF-beta
      superfamily, specifically the BMPs, CDMPs, OPs, and GDFs, have a dramatic effect
      on the development of bone and cartilage tissue. These growth factors help
      produce an extracellular matrix that can withstand extreme loading conditions in
      the body. In addition to growth factors, it is known that mechanical forces
      stimulate the synthesis of extracellular proteins in vitro and in vivo and can
      affect the tissue's overall structure. Load-bearing tissue, such as articular
      cartilage, will atrophy in the absence of mechanical forces, and this observation
      has caused researchers to incorporate mechanical stimulation into the tissue
      engineering process. This article focuses on the importance of mechanical forces
      in tissue engineering of articular cartilage and the growth factors that help
      stimulate the formation of load-bearing tissue.

PMID- 14582613
TI  - Comparative locomotory behavior of T lymphocytes versus T lymphoma cells on flat
      and grooved surfaces.
AB  - Locomotion is a characteristic of many cell types, including malignant cells. It
      is driven by a combination of interacting factors, one of which is recognized to
      be the surface microtopography. In this study, an in vitro analysis of cell
      migration was carried out to observe and quantify the differences in locomotion
      of two types of lymphoid cell on both flat and grooved surfaces. The cells
      studied were peripheral blood T lymphocytes (PBTL) and a malignant T lymphoma
      cell line (HUT78). It was found that, on the grooved pattern, the lymphoma HUT78
      cells were more diffusive in their migration than the T lymphocyte PBTL cells
      whereas, on the flat surface, the T lymphocyte PBTL cells had a more diffusive
      response than the T lymphoma HUT78 cells. It was also found that malignant T
      lymphoma cells are significantly slower and less diffusive when exposed to a
      plane substrate than when subjected to a grooved substrate. On the contrary, PBTL
      cells showed only a moderate drop in cell speed and diffusion on the grooved
      compared to the flat substrate. PBTL cells did, however, show a general alignment
      to the direction of the grooves whereas HUT78 did not. Therefore, we have found
      that the surface topography can influence the motile response of the two
      different T cell types in different ways, and this can be quantified in terms of
      motility parameters. This difference may have exploitable applications for cell
      sorting.

PMID- 14582615
TI  - Expression of in vivo mechanical strain upon different wave forms of exogenous
      forces in rabbit craniofacial sutures.
AB  - Sutures are fibrous joints between craniofacial bones, providing an interesting
      model for studying the biomechanics of the interface between soft and mineralized
      tissues. To explore whether different wave forms of exogenous forces induce
      corresponding sutural strain wave forms, sutural strain of the
      premaxillomaxillary suture (PMS) and nasofrontal suture (NFS) of New Zealand
      White rabbits (N = 8) was recorded upon application of static, sine- and square
      wave forces against the maxilla from 1 N to 5 N in 1 N increments. The PMS
      demonstrated compressive strain, whereas the NFS tensile strain. Despite a
      tenfold difference in peak PMS strain (- 1451 +/- 512 micro(epsilon)) and NFS
      strain (141 +/- 39 micro(epsilon)) in response to 5 N cyclic forces, wave forms
      of exogenous forces were expressed as corresponding wave forms of sutural strain
      in both the PMS and NFS. Peak sutural strain was similar upon static and sine
      wave cyclic loading. Thus, cells and matrix components of fibrous sutural tissue
      experience different wave forms of exogenous forces as corresponding wave forms
      of tissue-borne mechanical strain. Current craniofacial orthopedic therapies
      exclusively utilize static forces to change the shape of craniofacial bones via
      mechanically induced bone apposition and resorption. The present data provide
      room for exploring whether cyclic forces capable of inducing different sutural
      strain wave forms may accelerate sutural anabolic or catabolic responses.

PMID- 14582616
TI  - Initial burst measures of release kinetics from fiber matrices.
AB  - A comprehensive axisymmetric diffusion model of drug release from a fiber is
      developed to account for both the initial burst (IB) phenomenon as well as the
      later diffusion-dominated release. This model is an enhancement over previous
      models in that a set of four IB parameters are calculated, which both describe
      the initial burst phenomenon as well as improve the fit for the diffusion
      dominated release phase. This model is also an enhancement over previous models
      in allowing: finite dissolution volumes, finite stirring levels of the medium,
      and user-specified initial drug dispersion within the device. Five different drug
      release data sets are used to verify the model and to derive values for the IB
      parameters. Two of the data sets are from experiments conducted in this study,
      and the other three sets are from previously published data. These data sets were
      selected to cover a wide range of possibilities, i.e., from nearly 0% to nearly
      100% of the total drug release during IB, yet the model handles all cases equally
      well.

PMID- 14582617
TI  - Antimicrobial properties of lysozyme in relation to foodborne vegetative
      bacteria.
AB  - The purpose of this review is to describe the antibacterial properties and mode
      of action of lysozyme against gram-positive and gram-negative bacteria, and to
      provide insight in the underlying causes of bacterial resistance or sensitivity
      to lysozyme. Such insight improves our understanding of the role of this
      ubiquitous enzyme in antibacterial defense strategies in nature and provides a
      basis for the development and improvement of applications of this enzyme as an
      antibacterial agent. The bactericidal properties of lysozyme are primarily
      ascribed to its N-acetylmuramoylhydrolase enzymic activity, resulting in
      peptidoglycan hydrolysis and cell lysis. However, an increasing body of evidence
      supports the existence of a nonenzymic and/or nonlytic mode of action. Because
      gram-negative bacteria, including some major foodborne pathogens, are normally
      insensitive to lysozyme by virtue of their outer membrane that acts as a physical
      barrier preventing access of the enzyme, several strategies have been developed
      to extend the working spectrum of lysozyme to gram-negative bacteria. These
      include denaturation of lysozyme, modification of lysozyme by covalent attachment
      of polysaccharides, fatty acids and other compounds, attachment of C-terminal
      hydrophobic peptides to lysozyme by genetic modification, and the use of outer
      membrane permeabilizing agents such as EDTA or polycations or permeabilizing
      treatments such as high hydrostatic pressure treatment.

PMID- 14582618
TI  - Cell wall-deficient (CWD) bacterial pathogens: could amylotrophic lateral
      sclerosis (ALS) be due to one?
AB  - Recently, a number of diseases that had been thought previously to be caused by
      something other than an infectious agent are now known to be caused by bacteria.
      It now appears that it is not uncommon that bacteria, viruses, or fungi can cause
      diseases even when these organisms have not been detected or cultured. The most
      recent, well-publicized case is that of stomach ulcers; these are largely due to
      Helicobacter pylori infections. Here, the possibility is explored that
      amylotrophic lateral sclerosis (ALS) is caused by a cell wall-deficient
      microorganism.

PMID- 14582619
TI  - Distinguishing offensive from defensive biological weapons research.

PMID- 14582621
TI  - Ultrasound-assisted extraction of nitropolycyclic aromatic hydrocarbons from soil
      prior to gas chromatography-mass detection.
AB  - Continuous ultrasound-assisted extraction of nitropolycyclic aromatic
      hydrocarbons from soil prior to their individual separation and determination by
      gas chromatography (GC) with MS-MS detection is presented here. A multivariate
      optimisation of the variables affecting the continuous extraction step (namely,
      probe position, ultrasound radiation amplitude, percentage of duty cycle of
      ultrasonic exposure, sonication time, total extractant volume, extractant flow
      rate and temperature of the water-bath in which the extraction cell was placed)
      was performed. The method was compared with the reference EPA method 3540 using
      natural contaminated soils. Similar efficiencies were obtained but with a drastic
      reduction of both the extraction time (10 min versus 24 h) and the extractant
      volume (less than 10 ml versus 100 ml) by the proposed method. Detection limits
      of low picogram were obtained, with repeatability and reproducibility between
      4.21-5.70 and 5.20-7.23%, respectively.

PMID- 14582620
TI  - Signaling through protein kinases and transcriptional regulators in Candida
      albicans.
AB  - The human fungal pathogen Candida albicans switches from a budding yeast form to
      a polarized hyphal form in response to various external signals. This
      morphogenetic switching has been implicated in the development of pathogenicity.
      Several signaling pathways that regulate morphogenesis have been identified,
      including various transcription factors that either activate or repress hypha
      specific genes. Two well-characterized pathways include the MAP kinase cascade
      and cAMP-dependent protein kinase pathway that regulate the transcription factors
      Cph1p and Efg1p, respectively. cAMP also appears to interplay with other second
      messengers: Ca2+, inositol tri-phosphates in regulating yeast-hyphal transition.
      Other, less-characterized pathways include two component histidine kinases,
      cyclin-dependent kinase pathway, and condition specific pathways such as pH and
      embedded growth conditions. Nrg1 and Rfg1 function as transcriptional repressors
      of hyphal genes via recruitment of Tup1 co-repressor complex. Different upstream
      signals converge into a common downstream output during hyphal switch. The levels
      of expression of several genes have been shown to be associated with hyphal
      morphogenesis rather than with a specific hypha-inducing condition. Hyphal
      development is also linked to the expression of a range of other virulence
      factors. This review explains the relative contribution of multiple pathways that
      could be used by Candida albican cells to sense subtle differences in the growth
      conditions of its native host environment.

PMID- 14582622
TI  - Mesoporous polybutadiene-modified zirconia for high-temperature packed capillary
      liquid chromatography: column preparation and temperature programming stability.
AB  - In the present study, three different methods for packing of 3 microm PBD-ZrO2
      particles in 0.5 mm i.d. glass-lined stainless steel columns have been examined.
      The two first methods were based on a traditional downstream high-pressure
      technique using tetrachloromethane (Method I) or aqueous Triton X-100 (Method II)
      as slurry solvents, while Method III was an upstream high-pressure flocculating
      method with stirring, using isopropanol both as the slurry and packing solvent.
      Method I was found to be superior in terms of efficiency, producing 0.5 mm i.d. x
      10 cm columns with almost 90,000 plates m(-1) for toluene (R.S.D. = 8.7%, n = 3),
      using a slurry concentration of 600 mg ml(-1), ACN-water (50:50 (v/v)) as the
      packing solvent and a packing pressure of 650 bars. For Method I, the slurry
      concentration, column i.d., column length and initial packing pressure were found
      to have a significant effect on column efficiency. Finally, the long-term
      temperature stability of the prepared columns was investigated. In isothermal
      mode, using ACN-20 mM phosphate buffer, pH 7 (50:50 (v/v)) as the mobile phase,
      the columns were found to be stable for at least 3,000 void volumes at 100
      degrees C. At this temperature, the solute efficiencies changed about 5-18% and
      the retention factors changed about 6-8%. In temperature programming mode (not
      exceeding 100 degrees C), on the other hand, a rapid decrease in both column
      efficiency and retention factors was observed. However, when the columns were
      packed as initially described, ramped up and down from 50 to 100 degrees C for 48
      h and refilled, fairly stable columns with acceptable efficiencies were obtained.
      Although not fully regaining their initial efficiency after refilling, the solute
      efficiencies changed about 19-28% (32-37%) and the retention factors changed
      about 4-5% (13-17%) after running 3,000 (25,000) void volumes or 500 (3,900)
      temperature programs.

PMID- 14582623
TI  - Robust isocratic liquid chromatographic separation of functional poly(methyl
      methacrylate).
AB  - The separation of telechelic poly(methyl methacrylate) (PMMA) prepolymers based
      on the number of end-groups under critical liquid chromatography (LC) conditions
      has been studied using a bare-silica column, which can interact with polar
      functional groups. The critical solvent compositions for non-functional, mono
      functional and bi-functional PMMAs were determined in normal-phase LC using
      mixtures of acetonitrile and dichloromethane (DCM) of varying composition as the
      mobile phase. The telechelic prepolymers were successfully separated according to
      hydroxyl (OH) functionality (with zero, one, or two OH groups, respectively)
      under the critical conditions, in which fast (5 min), base-line separations were
      obtained independent of molecular weight. Changing the column temperature, flow
      rate, and mobile-phase composition within a certain range did not affect the
      functionality separation. Therefore this isocratic LC separation method is quite
      robust. Evaporative light-scattering detector (ELSD) calibration curves were used
      for the quantitative analysis of functional PMMA prepolymers.

PMID- 14582624
TI  - Optimization of a new mobile phase to know the complex and real polyphenolic
      composition: towards a total phenolic index using high-performance liquid
      chromatography.
AB  - An HPLC method is reported for the separation and quantification of five major
      polyphenolic groups found in fruits and related products: single ring phenolic
      acids (hydroxybenzoic acid and hydroxycinnamic acid derivatives), flavan-3-ols,
      flavonols, anthocyanins, and dihydrochalcones. A binary mobile phase consisting
      of 6% acetic acid in 2 mM sodium acetate aqueous solution (v/v, final pH 2.55)
      (solvent A) and acetonitrile (solvent B) was used. The use of sodium acetate was
      new and key to the near baseline separation of 25 phenolics commonly found in
      fruits. A photodiode array detector was used and data were collected at four
      wavelengths (280, 320, 360, and 520 nm). This method was sensitive and gave good
      separation of polyphenolics in apple, cherry, strawberry, blackberry, grape,
      apple juice, and a processing by-product. The improved separation has led to
      better understanding of the polyphenolic profiles of these fruits. Individual as
      well as total phenolic content was obtained, and the latter was close to and
      correlated well with that obtained by the Folin-Ciocalteu method (FC). The HPLC
      data can be used as a total phenolic index (TPI) for quantification of fruit
      phenolics, which is advantageous over the FC because it has more information on
      individual compounds.

PMID- 14582625
TI  - Separation of phytic acid and other related inositol phosphates by high
      performance ion chromatography and its applications.
AB  - A high-performance anion-exchange chromatographic method was developed for the
      separation of phytic acid and other inositol phosphates (myo-inositol bis-, tris
      , tetrakis-, and pentakisphosphates) with gradient elution and ultraviolet
      absorbance detection after post-column derivatization. With the acidic eluents,
      the combination of anion-exchange and ion suppression retention mechanisms led to
      the separation of 35 inositol phosphates (excluding enantiomers) into 27 peaks
      for the first time, and the retention behaviors of all myo-inositol bis- to
      hexakisphosphate isomers were studied. The whole separation procedure was
      completed within 65 min. Based on the investigations of nonenzymatic hydrolysis
      of phytic acid under different conditions by using this method, an in-house
      reference standard solution was produced, which can be used for method
      development. In addition, by applying this method to in vitro kinetic studies, at
      least one new enzymatic hydrolysis pathway of phytic acid was found, and one rule
      of enzymatic dephosphorylation of inositol phosphates (position effect) was
      proposed and another one (neighboring effect) was confirmed. The principle of the
      proposed identification approach for several inositol phosphate isomers based on
      hydrolysis products study will be applicable to other natural products analysis,
      for which standards are very expensive or not available.

PMID- 14582626
TI  - Determination of antioxidant migration levels from low-density polyethylene films
      into food simulants.
AB  - An analytical method for the determination of specific migration levels of
      phenolic antioxidants from low-density polyethylene (LDPE) into food simulant has
      been developed. The screening and response surface experimental designs to
      optimize the liquid-liquid extraction (LLE) of these antioxidants have been
      tested and the analyses have been carried out by reversed-phase high-performance
      liquid chromatography (HPLC) coupled with ultraviolet diode-array detector. The
      procedure developed has been applied to specific migration tests in different
      commercial LDPE films. The considered antioxidants have not been found upper the
      legislation limits although Ethanox 330 and Irgafos 168 have been found at trace
      level.

PMID- 14582627
TI  - Use of topological indices of polychlorinated biphenyls in structure-retention
      relationships.
AB  - Topological parameters (Balaban index and electrotopological index) were used as
      structural parameters in the structure-retention relationships (SRRs). These
      relationships were found to be statistically valid and useful in the prediction
      of retention data of polychlorinated biphenyls (PCBs) despite of the temperature
      program used in the gas chromatographic experiment.

PMID- 14582628
TI  - Optimization of headspace solid phase microextraction for gas chromatography/mass
      spectrometry analysis of widely different volatility and polarity terpenoids in
      olibanum.
AB  - The aim of this study was the optimization of headspace SPME conditions for
      trapping diterpenes present in frankincense (olibanum). Diterpenes like cembrenes
      or incensole and its derivatives are characteristic of olibanum. So in order to
      detect by SPME the occurrence of olibanum in archeological objects, it appears
      essential to have the best extraction conditions for these diterpenes that will
      be in very small quantities. Both sampling time and extraction temperature were
      studied and five fiber coatings were tested: polydimethylsiloxane (PDMS),
      polydimethylsiloxane/divinylbenzene (PDMS/DVB), carboxen/polydimethylsiloxane
      (CAR/PDMS), divinylbenzene/carboxen/polydimethylsiloxane (DVB/CAR/PDMS) and
      carbowax/divinylbenzene (CW/DVB). The PDMS/DVB fiber was found to be the most
      efficient for trapping olibanum characteristic diterpenes, with a sampling time
      of 1 h and a sampling temperature of 80 degrees C.

PMID- 14582629
TI  - Fingerprint profiling of acid hydrolyzates of polysaccharides extracted from the
      fruiting bodies and spores of Lingzhi by high-performance thin-layer
      chromatography.
AB  - Modern extraction and planar chromatographic instrumentation were employed for
      the fingerprint profiling of carbohydrates from an important and popular
      medicinal mushroom commonly known as Lingzhi. For the first time, the feasibility
      of employing the high-performance thin-layer chromatography (HPTLC) peak profiles
      (fingerprints) of carbohydrates for the screening of various Lingzhi
      species/products was demonstrated. An analytical procedure was developed such
      that upon acid hydrolysis of the polysaccharides extracted from various Lingzhi
      samples, fingerprint profiles that reveal the relative amounts of the degradation
      products, such as mono- and oligosaccharides, can be obtained using HPTLC plates
      (Si 50000) for separation and 4-aminobenzoic acid as the post-chromatographic
      derivatization reagent for detection. Also, using automated multiple development
      (AMD), the acid hydrolyzates from Lingzhi, consisting of simple and more complex
      sugars, can be separated simultaneously with high degree of automation. An
      important finding was that unique fingerprint patterns were observed in the
      monosaccharide profiles between two highly valued Lingzhi species, Ganoderma
      applanatum and Ganoderma lucidum, under total or partial acid hydrolysis
      conditions. Additionally, the HPTLC fingerprint profiles of carbohydrates were
      obtained from the extracts of the spores and fruiting bodies of Lingzhi and
      compared.

PMID- 14582630
TI  - Two-dimensional capillary electrophoresis involving capillary isoelectric
      focusing and capillary zone electrophoresis.
AB  - Capillary isoelectric focusing (cIEF) and capillary zone electrophoresis (CZE)
      was on-line hyphenated by a dialysis interface to achieve a 2D capillary
      electrophoresis (CE) system. The system was used with just one high-voltage power
      supply and three electrodes (one cathode shared by the two dimensions). The
      focused zone in the first dimension (i.e. the cIEF) was driven to the dialysis
      interface by electroosmotic flow (EOF), besides chemical mobilization from the
      first anode to the shared cathode. And then in the second dimension (i.e. the
      CZE), the separated zone was further separated and driven by an inverted EOF,
      which originated from the charged layer of a cationic surfactant adsorbed onto
      the inner wall of the capillary. Finally, a solution of ribonuclease was rapidly
      separated to assess the feasibility of the two-dimensional CE implement.

PMID- 14582631
TI  - Method development for the analysis of particle phase substituted methoxy phenols
      and aromatic acids from biomass burning using capillary
      electrophoresis/electrospray ionization mass spectrometry (CE/ESI-MS).
AB  - A method is developed for the determination of substituted methoxy phenols and
      aromatic acids in biomass burning aerosol using capillary electrophoresis (CE)
      coupled to an electrospray ionization mass spectrometer. Background electrolytes
      (BGEs) containing ammonium acetate, ammonium hydroxide and 10% (v/v) methanol at
      pH 9.1 and ammonium hydroxide at pH 11 are investigated for their suitability. A
      good linearity is found for all analytes in the range of 1-50 microM for the
      ammonium acetate based BGE and 1-40 microM for the ammonium hydroxide BGE. The
      detection limit ranged from 0.1 to 1.0 microM for the ammonium acetate based BGE
      and 0.3 to 0.7 microM for the ammonium hydroxide BGE. The relative standard
      deviation (R.S.D.) is typically less than 0.5% (ammonium acetate based BGE) and
      4.2% (ammonium hydroxide BGE) for the migration time and 3-9% (ammonium acetate
      based BGE) and 2.5-8% (ammonium hydroxide BGE) for the peak area (n = 5). The
      analytical time was less than 10 min for both methods. The proposed methods are
      fast, sensitive and quantitative and can be applied to the analysis of complex
      biomass burning aerosol samples without complex pre-treatment. The results from
      the analysis of real biomass burning samples demonstrate the suitability of the
      proposed methods to the analysis of low concentration water soluble organic
      carbon (WSOC) in biomass burning samples. The fast analytical time and high
      sensitivity of the proposed methods enables the analysis of a large number of
      size segregated impactor samples from biomass burning aerosols.

PMID- 14582632
TI  - Analyses of carcinogenic aromatic amines released from harmful azo colorants by
      Streptomyces SP. SS07.
AB  - Extracellular fluid protein (ECFP) of Streptomyces species SS07 has been used to
      reduce water soluble azo dyes and the carcinogenic amines released have been
      compared with that from chemical reduction. The effect of temperature, pH and
      contact time on the recovery of amines using ECFP was studied. The ECFP releases
      carcinogenic amines at a pH of 9.2 and a temperature of 37 degrees C for a
      contact period of 24 h. The reduction products were analyzed with HPLC and their
      structures confirmed by LC-MS and GC-MS. It was observed that both the ECFP and
      chemical reduction methods released similar type of amine products. In the case
      of dye samples, compared to chemical reduction, 5-20% increase in the release of
      carcinogenic amines by ECFP was observed. The percentage of amine products
      released by chemical reduction was higher for leather garment samples compared to
      ECFP treatment.

PMID- 14582634
TI  - Epidemiology of congenital hearing loss in Victoria, Australia.
AB  - The aim of this study was to report the incidence, prevalence and clinical
      characteristics of congenital hearing loss sufficient to require hearing aid
      fitting in the first 6 years of life for the 1993 birth cohort of the state of
      Victoria (population 4.4 million), Australia. In 1993, 64,116 infants born in the
      state of Victoria survived the neonatal period. Subjects included all children
      with congenital hearing loss for which hearing aids were fitted, at any time up
      to and including 31 December 1999, when the youngest member of the cohort reached
      6 years of age. Data on the degree, type and etiology of hearing loss were
      available from the Australian Hearing database for all subjects. Sociodemographic
      and health data were available from the Victorian Infant Hearing Screening
      Program (VIHSP) and parent questionnaires. The known prevalence of identified
      congenital hearing loss increased as the cohort aged. By the time the youngest
      member had reached the age of 6 years, 134 children (78 boys, 56 girls) had been
      fitted with hearing aids for permanent congenital hearing loss of any degree
      (2.09/1000). Fifty-four (40%) of these had known mild losses (20-40 dB HL). The
      prevalence of known moderate or greater loss (> 40 dB HL) was 1.12/1000; the data
      suggest that over 90% could have been detectable by neonatal hearing screening. A
      further seven children from the birth cohort were fitted with hearing aids due to
      acquired forms of hearing loss (0.11/1000). The etiology was known in only 57
      (43%) congenital cases, with known non-syndromal genetic causes accounting for 21
      (37%) of these. This study reports on the prevalence of congenital hearing loss
      requiring hearing aid fitting for an entire birth cohort. These data indicate the
      possible yield from neonatal screening, and hence the likely benefit of such
      screening. For a large proportion of cases, the etiology remains unknown. These
      data have implications for health service delivery and illustrate the usefulness
      of a population database in monitoring the prevalence of congenital hearing loss.

PMID- 14582633
TI  - Further clarifications on the parcel model.

PMID- 14582635
TI  - Auditory processing disorders in adults and children: evaluation of a test
      battery.
AB  - A Dutch test battery comprising six different tests for auditory processing
      disorders was evaluated in a group of 49 adults and children (age 8-57 years)
      with auditory complaints despite normal audiometric thresholds. Percentile scores
      were derived from normal control groups (n = 132) to determine whether a subject
      passed or failed a test. A composite score was computed to reflect a general
      score on all the auditory processing tests. In order to gain insight into
      underlying auditory processes, factor analysis was performed. Normal scores on
      all the tests were seen in five subjects. The remaining 44 subjects had at least
      one test score that was below the cut-off point (10th percentile). Factor
      analysis provided evidence for a model comprising four auditory components:
      auditory sequencing, word recognition in noise, auditory closure, and auditory
      patterning. This model could be useful in the interpretation of scoring patterns.
      Although there were some differences in scoring patterns between the children and
      adults, the test battery proved to be useful in both groups.

PMID- 14582636
TI  - The binaural interaction component (BIC) in children with central auditory
      processing disorders (CAPD).
AB  - The detection of binaural interaction is of diagnostic interest in patients with
      central auditory processing disorders (CAPDs), as binaural hearing tasks are
      frequently affected in these patients. Owing to the comorbidity associated with
      disorders such as an attention-deficit hyperactivity disorder, pathological
      results in subjective tests often show extra-auditory factors such as reduced
      attention rather than impaired central auditory function. Therefore, objective
      measures for auditory processing disorders are essential. The binaural
      interaction component (BIC), which is the arithmetical difference between the sum
      of the monaurally evoked auditory potentials of each ear and the binaurally
      evoked brainstem potentials, has been used as an objective measure of binaural
      interaction in humans. BIC measurements can therefore be considered as a possible
      diagnostic tool in CAPD patients. One aim of the present study was to examine
      whether and to what extent BIC measurements are capable of differentiating
      between normal children and children 'at risk for CAPD'. BIC measurements were
      performed on 17 children at risk for CAPD and in a group of 25 children with
      normal results in the central audiometric tests used. Using the presence or
      absence of clearly demonstrable BIC waveforms as an indication of whether a CAPD
      is present or not, a sensitivity and specificity of 76% could be achieved. We
      conclude that BIC measurements might be of some diagnostic value in CAPD
      patients.

PMID- 14582637
TI  - Minimal response levels for visual reinforcement audiometry in infants.
AB  - The aim of this study was to determine normative values for minimal response
      levels (MRLs) for normal-hearing young infants using insert earphone visual
      reinforcement audiometry (VRA). The subjects were 46 normally developing infants
      aged between 33 and 50 weeks who had hearing sensitivity assumed to be within
      normal limits and no evidence of middle ear dysfunction. VRA was carried out
      using insert earphones with warble tone stimuli, generated from an AC33
      audiometer and calibrated to ISO 389-2 for insert earphones in adults. The
      frequencies assessed were 500 Hz, 1 kHz, 2 kHz and 4 kHz. In total, 102 MRLs were
      obtained, with an approximately equal number of MRLs per frequency. Mean MRLs for
      500 Hz, 1 kHz, 2 kHz and 4kHz were 16 dB HL, 13 dB HL, 7 dB HL and 6 dB HL,
      respectively. Standard deviations were close to 6 dB for all frequencies. Mean
      MRLs at the lower frequencies were significantly greater than MRLs at the two
      higher frequencies. MRLs did not vary significantly with age. The results
      obtained from this study suggest significant infant adult differences when
      testing hearing using VRA with insert earphones, particularly at lower
      frequencies. Possible reasons for this and the clinical use of these normative
      values are discussed.

PMID- 14582638
TI  - New speech tests reveal benefit of wide-dynamic-range, fast-acting compression
      for consonant discrimination in children with moderate-to-profound hearing loss.
AB  - Fast-acting, wide-dynamic-range compression (WDRC) has been shown to give better
      discrimination of soft speech and shouted speech than linear amplification for
      moderately hearing-impaired young adults. For severe and profound hearing losses,
      higher compression ratios are needed. The resultant distortion of the temporal
      envelope and reduced modulation depth may offset improvements in audibility
      offered by WDRC. This study compares the effectiveness of WDRC and linear
      amplification for children with different degrees of hearing loss. Pre-recorded
      tests of closed-set consonant confusions and open-set word recognition were
      developed to assess performance. Three groups of subjects (aged 4-14 years) with
      moderate (51-70 dB), severe (71-90 dB) and profound (91-115 dB) hearing loss were
      fitted with hearing aids programmed with WDRC or linear amplification. The
      frequency response was adjusted to match each child's own hearing aid
      prescription. For each group, stimuli were presented both in quiet and in noise
      at levels chosen to avoid floor and ceiling effects. Consonant confusion scores
      for the profound and severe groups combined and for the moderate group were
      significantly better with WDRC than with linear amplification. Open-set test
      results showed greater variability. Although mean scores were higher for WDRC
      than for linear processing, the effects were of marginal statistical
      significance.

PMID- 14582639
TI  - Candidacy and the Children's Implant Profile: is our selection appropriate?
AB  - This study has two aims: first, to determine whether our paediatric Cochlear
      Implant Programme uses a modified version of the Children's Implant Profile
      (ChIP) in a consistent manner to inform candidacy decisions; and second, to
      establish whether our ratings of concern on the ChIP are predictive of speech
      discrimination, speech production and language outcomes. Retrospective data were
      collated over a 6-year period. For each ChIP category, ratings of 'no concern',
      'mild moderate concern' or 'great concern' were agreed for each child, and scores
      of 0, 1 or 2 were assigned respectively. During the period of study, of 147
      children assessed, 63% were considered to be suitable for cochlear implantation.
      A forward stepwise logistic regression showed that degree of concern on five of
      the ChIP factors significantly predicted the decision to implant. At 1 year and 3
      years after switch-on, the total ChIP score significantly predicted some speech
      perception outcomes, as did the degree of concern pre-implant regarding speech
      and language abilities and functional hearing. These concerns were also
      significantly predictive of receptive language ability and speech intelligibility
      ratings 3 years after implantation.

PMID- 14582641
TI  - What is new in proteomics? Biomarkers.

PMID- 14582640
TI  - Examination of differences between successful and unsuccessful elderly hearing
      aid candidates matched for age, hearing loss and gender.
AB  - This study examined group differences on a variety of measures for three groups
      of elderly hearing aid candidates matched for gender, age and hearing loss. These
      three groups were: (1) 26 candidates who declined amplification (non-adherents);
      (2) 24 individuals who purchased hearing aids, but subsequently returned them
      (rejected HA); and (3) 26 who purchased hearing aids and continued to use their
      hearing aids for at least the first 6 months following delivery (accepted HA).
      Following demonstration of adequate reliability for these measures, using the non
      adherents as the test retest study sample, group differences were examined for
      each pre-fit measure. The group of non-adherents who declined amplification
      differed from the two groups who purchased hearing aids on their scores for the
      Hearing Handicap Inventory for the Elderly (HHIE) and for several scales of the
      Communication Profile for the Hearing Impaired (CPHI) that assessed the
      individual's personal adjustment to hearing impairment. These findings were
      generally confirmed for the individual data, with the use of discriminant
      analysis. For the two groups who tried hearing aids, there were no group
      differences between those who retained them and those who did not. Discriminant
      analysis, however, indicated that those in the group who retained their (linear)
      hearing aids tended to have better finger dexterity and higher loudness
      discomfort levels than those who did not.

PMID- 14582642
TI  - CE/MS for quantitative metabolome analysis.

PMID- 14582643
TI  - Selective staining of proteins with hydrophobic surface sites on a native
      electrophoretic gel.
AB  - Chemical proteomics aims to characterize all of the proteins in the proteome with
      respect to their function, which is associated with their interaction with other
      molecules. We propose the identification of a subproteomic library of expressed
      proteins whose native structures are typified by the presence of hydrophobic
      surface sites, which are often involved in interactions with small molecules,
      membrane lipids, and other proteins, pertaining to their functions. We
      demonstrate that soluble globular proteins with hydrophobic surface sites can be
      detected selectively by staining on an electrophoretic gel run under
      nondenaturing conditions. The application of these staining techniques may help
      elucidate new catalytic, transport, and regulatory functionalities in complex
      proteomic screenings.

PMID- 14582644
TI  - Proteomics analysis of phosphotyrosyl-proteins in human lumbar cerebrospinal
      fluid.
AB  - Cerebrospinal fluid (CSF) is a secretion product of several different central
      nervous system (CNS) structures, including the choroid plexus in the ventricles.
      Pathological CNS processes are reflected in the protein composition of CSF. To
      elucidate the molecular events that occur in the homeostatic and pathological
      processes of the CNS, the high-throughput characterization of differentially
      expressed proteins, and of post-translationally modified proteins, is needed for
      proteomics studies of CSF. Among the post-translational modifications of
      proteins, phosphorylation is the most common and important mechanism for the
      reversible regulation of protein function. In this study, CSF phosphotyrosyl (p
      Tyr)-proteins were detected with antibodies and were analyzed with proteomics
      methods. Three different combination methods--1D gel electrophoresis and Western
      blotting, immunoprecipitation and 2D gel electrophoresis, and 2D gel
      electrophoresis and Western blotting--were used to detect p-Tyr-proteins in human
      lumbar CSF samples. Six protein spots, representing four proteins on a 2D Western
      blot, were identified as p-Tyr-proteins with the 2D gel electrophoresis and
      Western blotting method. Those four p-Tyr-proteins are kallikrein-6 precursor,
      complement C4 gamma-chain, gelsolin, and ceruloplasmin precursor. Additionally,
      four other nonphosphorylated CSF proteins--beta-2-glycoprotein I precursor,
      fibulin-1 precursor, EGF-containing fibulin-like extracellur matrix protein 1
      precursor, and angiotensinogen precursor--were characterized for the first time.

PMID- 14582645
TI  - Quantitative metabolome analysis using capillary electrophoresis mass
      spectrometry.
AB  - A new approach for the comprehensive and quantitative analysis of charged
      metabolites by capillary electrophoresis mass spectrometry (CE-MS) is proposed.
      Metabolites are first separated by CE based on charge and size and then
      selectively detected using MS by monitoring over a large range of m/z values.
      This method enabled the determination of 352 metabolic standards and its utility
      was demonstrated in the analysis of 1692 metabolites from Bacillus subtilis
      extracts, revealing significant changes in metabolites during B. subtilis
      sporulation.

PMID- 14582646
TI  - "Top Down" characterization is a complementary technique to peptide sequencing
      for identifying protein species in complex mixtures.
AB  - At present, mass spectrometry provides a rapid and sensitive means for making
      conclusive protein identifications from complex mixtures. Sequencing tryptic
      peptides derived from proteolyzed protein samples, also known as the "Bottom Up"
      approach, is the mass spectrometric gold standard for identifying unknowns. An
      alternative technology, "Top Down" characterization, is emerging as a viable
      option for protein identifications, which involves analyzing the intact unknowns
      for accurate mass and amino acid sequence tags. In this paper, both
      characterization methods were employed to more comprehensively differentiate two
      early-eluting peaks in a process-scale size-exclusion chromatography (SEC) step
      for a recombinant, immunoglobulin gamma-1 (IgG-1) fusion protein. The contents of
      each SEC peak were enzymatically digested, and the resulting peptides were mapped
      using reversed-phase (RP) HPLC-ion trap MS. Many low-level UV signals were
      observed among the fusion protein-related peptide peaks. These unknowns were
      collected, concentrated, and analyzed using nanoelectrospray (nanoES) collision
      induced dissociation (CID) tandem (MS/MS) mass spectrometry for identification.
      The peptide sequencing experiments resulted in the identification of twenty host
      cell-related proteins. Following peptide mapping, the contents of the two SEC
      peaks were protein mass profiled using on-line RP HPLC coupled to a high
      resolution, quadrupole time-of-flight (Qq/TOF) MS. Unknown proteins were also
      collected, concentrated, and dissociated using nanoES CID MS/MS. Intact protein
      CID experiments and accurate molecular weight information allowed for the
      identification of three full length host cell-derived proteins and numerous clips
      from these and additional proteins. The accurate molecular weight values allowed
      for the assignment of N- and C-terminal processing, which is difficult to
      conclusively access from peptide mapping data. The peptide-mapping experiments
      proved to be far more effective for making protein identifications from complex
      mixtures, whereas the protein mass profiling was useful for assessing
      modifications and distinguishing protein clips from full length species.

PMID- 14582648
TI  - Development of a system for the study of protein-protein interactions in planta:
      characterization of a TATA-box binding protein complex in Oryza sativa.
AB  - We describe a simple, rapid method for protein complex purification in planta.
      Using a biotin peptide as an affinity tag with TATA-box binding protein (TBP), 86
      unique proteins present in the purified complex were identified by tandem mass
      spectrometry. We identified proteins known to be associated with TBP, and many
      other proteins involved in pre-mRNA processing and chromatin remodeling. The
      identification of these novel protein-protein associations will upon further
      investigations provide new insights into the mechanisms of mRNA transcription and
      pre-mRNA processing.

PMID- 14582647
TI  - Proteomic analysis of the site specificity of glycation and carboxymethylation of
      ribonuclease.
AB  - Proteomic analysis using electrospray liquid chromatography-mass spectrometry
      (ESI-LC-MS) has been used to compare the sites of glycation (Amadori adduct
      formation) and carboxymethylation of RNase and to assess the role of the Amadori
      adduct in the formation of the advanced glycation end-product (AGE), N(epsilon)
      (carboxymethyl)lysine (CML). RNase (13.7 mg/mL, 1 mM) was incubated with glucose
      (0.4 M) at 37 degrees C for 14 days in phosphate buffer (0.2 M, pH 7.4) under
      air. On the basis of ESI-LC-MS of tryptic peptides, the major sites of glycation
      of RNase were, in order, K41, K7, K1, and K37. Three of these, in order, K41, K7,
      and K37 were also the major sites of CML formation. In other experiments, RNase
      was incubated under anaerobic conditions (1 mM DTPA, N2 purged) to form Amadori
      modified protein, which was then incubated under aerobic conditions to allow AGE
      formation. Again, the major sites of glycation were, in order, K41, K7, K1, and
      K37 and the major sites of carboxymethylation were K41, K7, and K37. RNase was
      also incubated with 1-5 mM glyoxal, substantially more than is formed by
      autoxidation of glucose under experimental conditions, but there was only trace
      modification of lysine residues, primarily at K41. We conclude the following: (1)
      that the primary route to formation of CML is by autoxidation of Amadori adducts
      on protein, rather than by glyoxal generated on autoxidation of glucose; and (2)
      that carboxymethylation, like glycation, is a site-specific modification of
      protein affected by neighboring amino acids and bound ligands, such as phosphate
      or phosphorylated compounds. Even when the overall extent of protein modification
      is low, localization of a high proportion of the modifications at a few reactive
      sites might have important implications for understanding losses in protein
      functionality in aging and diabetes and also for the design of AGE inhibitors.

PMID- 14582649
TI  - Proteome of Haemophilus ducreyi by 2-D SDS-PAGE and mass spectrometry: strain
      variation, virulence, and carbohydrate expression.
AB  - We have analyzed the proteome of several strains of Haemophilus ducreyi by two
      dimensional gel electrophoresis (2-DE) and mass spectrometry. Over 100 spots were
      analyzed from the soluble and insoluble protein fractions from the prototype
      strain 35000HP and 122 distinct proteins were identified. Functions of
      approximately 80% of the 122 proteins were deduced by identification with close
      homologues of Haemophilus influenzae. Four additional wild type and three mutant
      strains were also analyzed that vary in their virulence and/or outer-membrane
      lipooligosaccharide structures. Overall, the 2-DE gel maps of the wild type and
      mutant strains were similar to strain 35000HP, suggesting little proteome
      diversity in relation to carbohydrate expression and/or virulence. An exception
      was the Kenyan strain 33921 which contained significant differences in its
      proteome 2-DE map and also synthesizes an unusual LOS with a trisaccharide branch
      structure. This African strain may represent a prototype of a second clonal group
      of H. ducreyi.

PMID- 14582650
TI  - Liquid- and gas-phase nitration of bovine serum albumin studied by LC-MS and LC
      MS/MS using monolithic columns.
AB  - Post-translational nitration of proteins was analyzed by capillary reversed-phase
      high-performance liquid chromatography (RP-HPLC) on-line interfaced to
      electrospray ionization mass spectrometry (ESI--MS) or tandem mass spectrometry
      (ESI--MS/MS). Both methods were compared using a tryptic digest of bovine serum
      albumin (BSA) and yielded sequence coverages of 95% and 33% with RP-HPLC--ESI--MS
      and RP-HPLC--ESI--MS/MS, respectively. At least 95% of the tyrosines were covered
      by the former method, whereas the latter method only detected less than 50% of
      the tyrosine-containing peptides. Upon liquid-phase nitration of BSA in aqueous
      solution using an excess of tetranitromethane, at least 16 of the 20 tyrosine
      residues were found to be nitrated. After exposure of solid BSA samples to
      gaseous nitrogen dioxide and ozone at atmospherically relevant concentration
      levels, only 3 nitrated peptides were detected. By use of such a model system, RP
      HPLC--ESI--MS proved to be a rapid and highly efficient method for the
      comprehensive and quantitative detection of protein nitration.

PMID- 14582651
TI  - Development and applications of in-gel CNBr/tryptic digestion combined with mass
      spectrometry for the analysis of membrane proteins.
AB  - Hydrophobic membrane proteins often have complex functions and are thus of great
      interest. However, their analysis presents a challenge because they are not
      readily soluble in polar solvents and often undergo aggregation. We present a
      sequential CNBr and trypsin in-gel digestion method combined with mass
      spectrometry for membrane protein analysis. CNBr selectively cleaves methionine
      residues. But due to the low number of methionines in proteins, CNBr cleavage
      produces a small number of large peptide fragments with MWs typically >2000,
      which are difficult to extract from gel pieces. To produce a larger number of
      smaller peptides than that obtained by using CNBr alone, we demonstrate that
      trypsin can be used to further digest the sample in gel. The use of n-octyl
      glucoside (n-OG) to enhance the digestion efficiency and peptide recovery was
      also studied. We demonstrate that the sensitivity of this membrane protein
      identification method is in the tens of picomole regime, which is compatible to
      the Coomassie staining gel-spot visualization method, and is more sensitive than
      other techniques reported in the literature. This CNBr/trypsin in-gel digestion
      method is also found to be very reproducible and has been successfully applied
      for the analysis of complex protein mixtures extracted from biological samples.
      The results are presented from a study of the analysis of bacteriorhodopsin,
      nitrate reductase 1 gamma chain, and a complex protein mixture extracted from the
      endoplasmic recticulum membrane of mouse liver.

PMID- 14582652
TI  - Gene microarray study corroborates proteomic findings in rodent islet cells.
AB  - As reported in an issue of Journal of Proteome Research, mass spectrometry has
      been used to identify numerous proteins in pancreatic islets. Our group studies
      beta cell gene expression, and we were interested in whether proteins described
      in this study could be found at the level of the transcriptome. Microarray
      analysis is a powerful technique for quantitative measurements of the expression
      of thousand genes in parallel. However, in crude tumor biopsies, only a subset of
      transcripts correlate with protein levels, and it is still unknown how frequently
      mRNA expression correlates with amount of protein in well-differentiated cells.
      To address this issue, we presently compared data from mouse primary islet
      proteins obtained by proteomic analysis with RNA data from FACS purified primary
      rat beta cells obtained by microarray analysis (Rasschaert J, Liu D, Cardozo AK,
      Kutlu B, Eizirik DL, manuscript in preparation).

PMID- 14582653
TI  - Proteomic analysis of the genetic premature aging disease Hutchinson Gilford
      progeria syndrome reveals differential protein expression and glycosylation.
AB  - Proteomics has revealed differential protein expression and glycosylation in
      membrane proteins from premature aging Hutchinson-Gilford progeria syndrome
      fibroblasts (progeria). Progeria is a rare autosomal dominant genetic disorder of
      premature aging characterized by marked growth retardation and specific,
      progressive, premature senescent changes of the skin and other tissues. Affected
      children live to an average age of 13 years. The 1q20-24 region of chromosome 1
      which codes for one of these proteins, lamin A/C, has previously been implicated
      by Brown et al. (1990) who described identical twins with progeria, where
      cytogenetic analysis showed an inverted insertion in the long arm of the
      chromosome in 70% of cells. Luengo et al. (2002) similarly reported an
      interstitial deletion of chromosome 1q23, in a 9-year-old patient with a classic
      clinical picture of progeria.

PMID- 14582654
TI  - Sealing porous nanovesicles--solutions inspired by primordial biosystems.
AB  - Microcapsules designed for slow drug release have preferably some porosity. There
      are, however, applications in which a hermetical sealing of the microcapsules is
      desired. Sealing is not a trivial problem and could be necessary to durably
      encapsulate toxic compounds which cannot be eliminated from the body, or to
      encapsulate harmful substances stored in the atmosphere. Nature may have one
      solution: Nanobacteria have developed surprisingly simple mechanisms to access
      and use primal energies, and to survive arid periods by sealing their surface.

PMID- 14582655
TI  - What is your diagnosis? Dilated cardiomyopathy (DCM) causing congestive heart
      failure.

PMID- 14582656
TI  - Total ear canal ablation in the cat: indications, morbidity and long-term
      survival.
AB  - Fifty-two total ear canal ablation (TECA) procedures in 44 cats were reviewed.
      The indication for surgery was neoplasia in 41 per cent of the cats, 86 per cent
      of which had ceruminous gland adenocarcinoma. Chronic inflammatory or polypoid
      disease accounted for 50 per cent of surgical procedures. Postoperative
      complications included Horner's syndrome (42 per cent) and facial paralysis (56
      per cent) and these were permanent in 14 per cent and 28 per cent of cases,
      respectively, with the rest resolving in the ensuing weeks or months. The higher
      incidence of Horner's syndrome and facial paralysis in the cat, compared to the
      dog, was attributed to greater fragility of the feline tympanic plexus and facial
      nerve. The median survival time of cats with ceruminous gland adenocarcinoma was
      50-3 months, and did not differ significantly from that for inflammatory or
      polypoid disease. A potential prognostic indicator for this tumour was the
      mitotic index (MI): cases with MI < or = 2 survived significantly longer than
      those with MI > or = 3.

PMID- 14582657
TI  - Evaluation of a continuous glucose monitoring system in diabetic dogs.
AB  - The generation of a blood glucose curve is important for assessing the response
      to insulin therapy in diabetic dogs. Disadvantages of this technique include
      patient discomfort and the potential for missing transient hypo- or
      hyperglycaemic episodes. The aim of the current study was to evaluate a
      continuous glucose monitoring system (CGMS) for use in diabetic dogs.
      Interstitial fluid glucose concentrations were recorded in 10 diabetic dogs,
      every five minutes for up to 48 hours, using a subcutaneous sensor attached to
      the CGMS device. Blood glucose concentrations were measured simultaneously using
      a glucometer. The correlation between interstitial fluid and blood glucose values
      was 0.81 (P < 0.01). The largest discrepancies between the two sets of data were
      seen during the one- to three-hour period following feeding, suggesting that
      postprandial hyperglycaemia might not be reflected in the interstitial fluid. The
      authors conclude that the CGMS is a potentially valuable tool in the management
      of canine diabetic patients.

PMID- 14582658
TI  - Analysis of canine and feline haemograms using the VetScan HMT analyser.
AB  - The VetScan HMT is an impedance counter haematology analyser which produces a
      full blood count and three-part white blood cell differential. The aim of this
      study was to compare the results generated by the analyser with those obtained by
      standard methods used routinely in the authors' laboratory. Blood samples from 68
      dogs and 59 cats were run on the VetScan HMT analyser and also subjected to
      reference methods, and the results obtained were compared. Correlation
      coefficients (feline/canine) were: 0.97/0.99 for haematocrit (Hct), 0.98/0.99 for
      haemoglobin (Hb), 0.81/0.98 for total white blood cells (WBC), and 0.89/0.97 for
      granulocyte and 0.65/0.93 for platelet counts. Coefficients for lymphocyte counts
      were 0.25/0.28 and for monocyte counts were 0.12/0.79. In conclusion, the VetScan
      HMT performed well on canine samples, showing excellent correlation for canine
      Hct, Hb, RBC, WBC, granulocyte and platelet counts. For feline samples, although
      there was excellent correlation for Hct, Hb and RBC, the WBC and three-part white
      blood cell differential and platelet count should be interpreted with caution as
      they can be unreliable.

PMID- 14582659
TI  - Sterile nodular panniculitis and pansteatitis in three weimaraners.
AB  - The clinical and pathological findings in three unrelated weimaraners with
      pyrexia and multiple subcutaneous nodules are reported. Abdominal pain was an
      additional feature in two of the dogs and clinical investigations revealed
      inflammation of subcutaneous, mesenteric and falciform fat. Histopathological
      findings were consistent with pansteatitis. In the third dog, lesions were
      apparently limited to the subcutis and, hence, a diagnosis of nodular
      panniculitis was made. Microbiological examination of tissues was negative in all
      dogs, and there was no evidence of pancreatic disease. This report thus describes
      a presumed sterile and idiopathic panniculitis/pansteatitis complex in weimaraner
      dogs. Although the aetiology is unknown, this may represent an immune-mediated
      disorder.

PMID- 14582660
TI  - Complete patellar ligament replacement using a fascia lata autograft in a dog.
AB  - A novel technique for the repair of a chronically lacerated patellar ligament in
      a pet greyhound is described. The injury had been sustained traumatically, and a
      previous surgical repair had proved unsuccessful. On further surgical
      investigation, identification of the ruptured ligament ends was not possible. A
      double fascia lata graft was employed to reconstruct the lateral and medial
      portions of the ligament. This repair was augmented with 27 kg monofilament nylon
      anchored through tunnels from the proximal tibia to the patella and quadriceps
      tendon. A concurrent skin deficit was managed with a superficial epigastric axial
      pattern flap. To the authors' knowledge, only one previous case requiring
      complete patellar ligament replacement has been documented in the veterinary
      literature. This report details a simplified surgical technique which may have
      advantages over the previously described technique.

PMID- 14582661
TI  - Passive liver congestion associated with caudal vena caval compression due to
      oesophageal leiomyoma.
AB  - A large caudodorsal mediastinal mass was identified in a dog which had been
      presented for vomiting and anorexia. A few weeks later, the dog developed ascites
      and hindlimb oedema. Radiography showed that the caudodorsal mediastinal mass was
      compressing the caudal vena cava, probably inducing passive congestion of the
      liver. At postmortem examination, the mass was diagnosed as a large oesophageal
      leiomyoma. To the authors' knowledge, an oesophageal tumour leading to
      compression of the caudal vena cava associated with passive congestion of the
      liver has not been described previously in dogs. Secondary signs relating to the
      oesophageal mass appeared to be more prominent than the digestive signs. Causes
      of passive congestion of the liver and the differential diagnoses for a
      caudodorsal mediastinal mass are discussed.

PMID- 14582662
TI  - Pulmonary adenocarcinoma with osteoblastic bone metastases in a cat.
AB  - A 12-year-old male cat with depression and dyspnoea was presented for
      investigation. Radiography and computed tomography revealed hydrothorax and solid
      masses involving the sternum, ribs and thoracic vertebrae. The cat died two days
      after first presentation, and postmortem examination revealed lung masses and
      proliferative bony lesions. Histologically, a neoplastic proliferation of
      epithelial cells was seen in the lungs, with a large amount of collagen and
      deposits of cholesterin. The bone lesions were also composed of neoplastic
      epithelial cells and abundant calcified osteoid, without atypia. A diagnosis of
      pulmonary adenocarcinoma with osteoblastic bone metastases was made. This is the
      first reported case of osteoblastic metastases in the cat.

PMID- 14582664
TI  - Do rising pet insurance payouts spell trouble for vets and insurers alike?

PMID- 14582663
TI  - Exploring the potential of physiotherapy.

PMID- 14582665
TI  - On the association between genes and complex traits.

PMID- 14582666
TI  - Alopecia areata: autoimmunity--the evidence is compelling.
AB  - There is strong evidence indicating that alopecia areata is a tissue-specific,
      autoimmune disease. Hair loss is associated with a perifollicular lymphocytic
      infiltrate made up primarily of CD4+ cells, along with a CD8+ intrafollicular
      infiltrate. Evidence of immune activation includes expression of HLA-DR; HLA
      A,B,C; and ICAM-1 on the follicular epithelium. It is likely that the follicular
      expression of HLA-DR and ICAM-1 is induced by interferon-gamma produced by T
      cells. Antibodies to follicular epithelium are often present, but their
      significance is not known. Lesional scalp from alopecia areata patients grafted
      onto nude mice regrows hair coincident with a loss of infiltrating lymphocytes
      from the graft. Hair loss can be transferred to human scalp explants on SCID mice
      by injection of lesional T cells. It is necessary to activate the T cells by
      culture with follicular autoantigens. Melanocyte-associated antigens are also
      capable of activating T cells to induce hair loss, suggesting that they are
      capable of functioning as autoantigens for alopecia areata. Parallel evidence in
      rodent models of spontaneous alopecia areata also strongly supports a role for T
      cells in the pathogenesis of this condition.

PMID- 14582667
TI  - Mechanisms of immune privilege in the eye and hair follicle.
AB  - It has been recognized for over a century that the eye is endowed with remarkable
      properties that permit the long-term survival of foreign tumor and tissue grafts
      that are normally rejected at extraocular sites. This ocular immune privilege was
      originally attributed to a putative sequestration of antigens in the eye as a
      result of the conspicuous absence of intraocular lymphatic drainage channels. In
      the last 30 years, a sizeable body of information indicates that ocular immune
      privilege is a product of multiple anatomical, physiological, and
      immunoregulatory processes. Ocular tissues and fluids express a wide variety of
      anti-inflammatory and immunosuppressive molecules, including CD95L (FasL),
      transforming growth factor-beta, macrophage migration inhibitory factor, alpha
      melanocyte-stimulating hormone, calcitonin gene-related peptide, somatostatin,
      and complement regulatory proteins. Moreover, antigens entering the anterior
      chamber of the eye evoke a unique form of immune deviation that culminates in the
      antigen-specific suppression of TH1 immune responses. Finally, the intraocular
      milieu contains both cell membrane and soluble factors that inhibit both the
      adaptive and innate immune systems. The hair follicle is also recognized for its
      immune privilege. Like the anterior chamber of the eye, it produces anti
      inflammatory and immunosuppressive cytokines, such as transforming growth factor
      beta and adrenocorticotrophic hormone. The cells of the hair follicle display
      limited expression of class Ia MHC molecules and, like cells that line the
      anterior chamber of the eye, are protected against CD8+ cytotoxic T lymphocyte
      attack. Gaining a better understanding of the immune privilege of the hair
      follicle may provide insights into the regulation and pathogenesis of immune
      mediated diseases of the skin.

PMID- 14582668
TI  - Mouse alopecia areata models: an array of data on mechanisms and genetics.
AB  - Laboratory mice have become the premier animal model for most human and domestic
      animal diseases, and they have long been the model of choice for studying
      mammalian genetics, especially since the advent of genetic engineering. Many
      remarkable discoveries have been made through intense study of these wonderful
      small mammals, and undoubtably many more will be made. It is no surprise that one
      mouse model for alopecia areata (AA) has been found possibly many more will be,
      some of which exhibit rare phenotypes found in subpopulations of humans with the
      disease, such as nail deformities, thyroid disease, inflammatory bowel disease,
      and autoimmune polyendocrine syndrome type 1. Intense investigation by many
      groups into the first model, the adult onset form of AA (using the C3H/HeJ inbred
      strain), found similarities as well as differences with commonly held ideas
      concerning human AA. Regardless of some of the controversies, much insight has
      been gained from studying these and other rodent and domestic animal models which
      has opened up new ideas and discussions of AA and its treatment.

PMID- 14582669
TI  - Characterization of hair follicle antigens targeted by the anti-hair follicle
      immune response.
AB  - Alopecia areata is a common disfiguring hair loss disorder that primarily affects
      the hair follicle as it enters the prolonged growth phase called anagen. The last
      few years have yielded an explosion of more rigorously obtained data on the
      etiology and pathogenesis of this disorder. While a consensus is rapidly building
      in support of an autoimmune pathogenesis, there are still several enigmatic
      issues to be resolved. These include the possibility that alopecia areata is
      really a multientity disorder with causes that are multifactorial. This will have
      important implications for the research scientist's search for the jigsaw
      puzzle's largest missing piece--the identification of the target autoantigen(s).
      There is now much evidence that autoimmune diseases with both T and B cell
      components have shared target autoantigens/epitopes. It is likely that alopecia
      areata is similar, as there is now very strong evidence for the generation of
      autoantibodies as well as autoreactive T cells to hair follicles in the
      pathogenesis of this disease. The following brief review outlines the progress we
      have made over the last five to ten years in the characterization of hair
      follicle antigens targeted by antibodies in alopecia areata. Results of these
      studies now show that the elicitation of antibodies to hair follicle-specific
      proteins is a highly conserved phenomenon in all affected species studied to
      date. Candidate autoantigens that have been identified include the 44/46 kDa hair
      specific keratin (expressed in the precortical zone of anagen hair follicles) and
      trichohyalin (an important intermediate filament-associated protein) expressed in
      the inner root sheath of the growing hair follicle. Moreover, there is evidence
      that anti-hair follicle antibodies are modulated during the disease process, can
      occur before clinically detectable hair loss, and may be reduced in titer during
      successful treatment. Preliminary data from passive transfer experiments suggest
      that in some species these antibodies may disrupt hair cycling. We are currently
      applying a more molecular approach (e.g., cDNA library screening) to identify
      hair follicle antigens truly associated with the onset of the disorder.

PMID- 14582670
TI  - Alopecia areata susceptibility in rodent models.
AB  - With our current view of alopecia areata as an autoimmune disease, it is probable
      that disease development in an individual is dependent on multiple genetic and
      environmental factors interacting in a complex system. Rodent models afford the
      opportunity to investigate alopecia areata development and to define the
      significance of the different factors involved. Recently, rodent model
      characterization has been conducted using flow cytometry, microarray analysis,
      and functional studies. From these a pattern of events in alopecia areata
      development has emerged. Although the preliminary activation events for the onset
      of alopecia areata remain unknown, the response of the immune system is
      characterized by antigen presentation and costimulation of lymphocytes in the
      lymph nodes and skin, a deficiency of CD4+/CD25+ regulatory cells, and an action
      of activated lymphocytes on hair follicles via Fas/FasL signaling and cytokines.
      Thus, onset of disease may require appropriate (or inappropriate) expression of
      stimulatory antigens within the hair follicle, the breakdown of the putative hair
      follicle immune privilege, the presentation of antigens to the immune system, a
      failure of immune system regulation, and the ability of the activated immune
      system to disrupt anagen-stage hair follicles. Once the sequence of events is
      initiated, it may become a self-perpetuating cycle, with epitope spreading
      leading to a wider range of targets in chronic alopecia areata. Rodent model
      studies have provided significant insight into alopecia areata, but much more
      remains to be explained about the mechanisms of disease development.

PMID- 14582671
TI  - The hair follicle and immune privilege.
AB  - This essay reviews the available evidence that the proximal hair follicle
      epithelium generates and maintains an area of relative immune privilege during a
      defined segment of the hair cycle (i.e., during anagen). This immune privilege is
      chiefly characterized by a very low level of expression of MHC class Ia antigens
      and by the local production of potent immunosuppressive agents, such as alpha-MSH
      and TGF-beta1. We discuss the putative functions of immune privilige of the
      anagen hair bulb, favoring the view that immune privilege serves mainly to
      sequester anagen- and/or melanogenesis-associated autoantigens from immune
      recognition by autoreactive CD8+ T cells. On this basis, we develop how the
      "immune privilege collapse model" of alopecia areata pathogenesis was conceived.
      In our discussion of the clinical implications of immune privilege, we outline
      the currently available evidence in support of this still hypothetical scenario
      to explain the initiation, progression, and termination of alopecia areata
      lesions. We review the most recent evidence from our laboratory that alpha-MSH,
      IGF-1, and TGF-beta1 can downregulate IFN-gamma-induced ectopic MHC class I
      expression in human anagen hair bulbs in vitro. Finally, we suggest that hair
      follicle-derived alpha-MSH, IGF-gamma, and TGF-beta1 form part of a
      constitutively active "IP restoration machinery" of the anagen hair bulb, which
      we propose to be recruited whenever the hair follicle suffers immune injury.
      Finally, we sketch some particularly promising avenues for future investigation
      into the far too long ignored hair follicle immune privilege.

PMID- 14582672
TI  - Neurotrophins and their role in pathogenesis of alopecia areata.
AB  - Neurotrophins comprise a family of structurally and functionally related proteins
      that are critical for the development and maintenance of cutaneous innervation.
      They also fulfill multiple non-neurotrophic functions in skin, including
      regulation of epidermal proliferation and apoptosis, control of hair follicle
      development and cycling, and melanogenesis. Numerous indications suggest that
      neurotrophins play an important role in the pathogenesis of a variety of
      autoimmune diseases. In this review, we focus on the role of neurotrophins in the
      pathogenesis of alopecia areata, an autoimmune disorder that affects actively
      growing hair follicles. Recent data suggest that neurotrophins and their
      receptors are differentially expressed among the subsets of immune cells in
      alopecia areata-affected skin. Experimental data suggest that neurotrophins may
      regulate both the cyclic activity of the hair follicle and the functions of
      immune cells of inflammatory infiltrates. Additional research is required to
      bridge the gap between our current knowledge of neurotrophin functions in skin
      affected by alopecia areata and our knowledge of their potential clinical
      applications. Progress in this area of research will hopefully lead to the
      development of multiple applications for neurotrophins and their
      agonists/antagonists in alopecia areata and other hair growth disorders.

PMID- 14582673
TI  - Genetic linkage studies in alopecia areata.
AB  - Alopecia areata affects approximately 4.6 million individuals in the United
      States alone. It is typified by patchy hair loss on the scalp that can progress
      to cover the entire scalp (alopecia totalis) and eventually the entire body
      (alopecia universalis). Despite the high incidence of this condition, its genetic
      basis is largely unknown. It is now generally accepted, however, that it fits the
      paradigm of a complex trait, in which a combination of genetic and environmental
      factors results in the final phenotype. Genetic studies have been limited thus
      far to association analyses, which suggest that a permissive HLA status may
      potentiate the development of alopecia areata. A systematic screen for
      identifying the primary genetic mechanisms underlying this disorder has never
      before been undertaken, however. Here we discuss our approach to the
      identification of susceptibility genes for alopecia areata. In particular, we
      recently initiated a comprehensive genetic analysis by performing a genome-wide
      scan in a collection of alopecia families with multiple affected family members.
      There are currently a number of examples of complex diseases of the skin, such as
      psoriasis and atopic dermatitis, in which genetic studies are being undertaken
      that substantiate the timeliness of this approach. We anticipate that these
      studies will lead to the identification of the susceptibility genes and provide a
      foundation for understanding how they interact with each other and with other
      variables, such as the immune system and environmental factors.

PMID- 14582674
TI  - Gene delivery to the hair follicle.
AB  - Skin and appendages such as hair follicles are attractive candidates for gene
      therapy targets because they are easily accessible and can be removed and
      genetically manipulated in culture. Hair follicles are of special interest
      because our understanding of hair follicle biology and pathophysiology has
      progressed significantly in recent years, and we now have a much better
      understanding of how genes, encoding transcription factors, growth factors, and
      cytokines regulate both hair follicle development and the cycles of hair follicle
      growth (anagen, catagen, and telogen) (Cotsarelis and Millar, 2001; Millar,
      2002). Also important is the characterization of an increasing number of genetic
      mutations that affect hair growth and can result in hair loss (Cotsarelis and
      Millar, 2001). Gene therapy could be used to introduce genes that manipulate hair
      follicle growth and cycling or that replace the mutated defective gene with a
      normal wild-type gene. As our understanding of the polygenic basis for a number
      of alopecias improves, gene-based therapies might also be designed to provide
      more promising treatments than current palliative therapies for hair loss. This
      review will describe some of the recent progress in gene delivery to hair
      follicles and discuss examples of how gene delivery can cause phenotypic changes
      in hair follicles.

PMID- 14582675
TI  - Therapy of alopecia areata: on the cusp and in the future.
AB  - Over the past decade, basic research has established alopecia areata as a T cell
      mediated autoimmune disease and has clarified many of its genetic, cellular, and
      molecular aspects. Perifollicular and intrafollicular mononuclear cell
      infiltrates directed at anagen hair bulbs are characteristic and striking
      histologic features in early alopecia areata. The inflammatory infiltrate is
      composed predominantly of activated CD4+ and CD8+ T cells, together with
      macrophages and Langerhans cells. The initiation phase of alopecia areata is
      mediated by type 1 cytokines, including interleukin-2, interferon-gamma, and
      tumor necrosis factor-alpha. Like other diseases with a strong autoimmune
      component, alopecia areata has associated with it specific human leukocyte
      antigens, which determine susceptibility, severity, chronicity, and resistance.
      New topical immunomodulating drugs and biologic therapies that have been
      developed, or that are in development, for the treatment of other immune-mediated
      inflammatory skin diseases will likely be effective in alopecia areata as well.
      The present discussion addresses the treatment of alopecia areata within the
      framework of these new modalities.

PMID- 14582676
TI  - Old wine in new bottles: reviving old therapies for alopecia areata using rodent
      models.
AB  - Alopecia areata is regarded as a tissue-restricted autoimmune disease of hair
      follicles in which follicular activity is arrested because of the continued
      activity of lymphocytic infiltrates. Actual loss of hair follicles does not
      occur, even in hairless lesions. A variety of immunomodulating therapies,
      including contact sensitizers and immunomodulators, are part of the usual
      armamentarium for this disorder. None of these treatments have been consistent in
      their efficacy, and many have untoward side effects. Nevertheless, their uses in
      valid animal models provide a tool to dissect out molecular mechanisms of
      therapeutic effects. For several decades, both mechlorethamine (for the treatment
      of cutaneous T cell lymphoma) and anthralin (for the treatment of psoriasis) have
      been used successfully. When these therapies were tested in rat and mouse
      alopecia areata models, we found anthralin and mechlorethamine to be the most
      effective topical modalities, respectively. The underlying cellular mechanisms
      may act through targeting infiltrative lymphocytes, and the molecular mechanisms
      may involve specific cytokine expression changes. These visible, accessible, and
      unilaterally treated animal model systems are ideal for studying novel alopecia
      areata therapies, particularly in terms of their in vivo molecular mechanisms of
      action.

PMID- 14582677
TI  - The new biologics in psoriasis: possible treatments for alopecia areata.
AB  - Therapeutics in alopecia areata (AA) have remained relatively unchanged for many
      years, with few treatments having more than moderate effects in severely affected
      patients. The advent of the new biologic medications in the dermatologic world,
      however, particularly in psoriasis treatment, introduces possibilities of
      treatment for many other immune-mediated diseases.

PMID- 14582679
TI  - How close are we to solving the puzzle? Review of the Alopecia Areata Research
      Workshop David Norris.

PMID- 14582678
TI  - Alopecia areata registry: an overview.
AB  - The National Alopecia Areata Registry was awarded as a five-year contract by
      NIAMS to promote research on the genetic basis of alopecia areata. The registry
      is Web based and can be accessed online at http://www. AlopeciaAreata
      Registry.org. Samples of DNA, lymphoblast lines, and sera, as well as
      epidemiology and quality-of-life data, are being collected from well
      characterized individuals, multiplex families, and sib pairs for future research
      studies and investigators.

PMID- 14582680
TI  - The CLESA project.

PMID- 14582681
TI  - Cross-national determinants of quality of life from six longitudinal studies on
      aging: the CLESA project.
AB  - BACKGROUND AND AIMS: The Comparison of Longitudinal European Studies on Aging
      (CLESA) Project, here presented for the first time, is a collaborative study
      involving five European and one Israeli longitudinal study on aging. The aim of
      this paper is to describe the methodology developed for the harmonization of data
      and the creation of a Common Data Base (CDB), and to investigate the distribution
      of some selected common variables among the six countries. The design of each
      study is briefly introduced and the methodology leading to the harmonization of
      the common variables is described. METHODS: The study base includes data from
      five European countries (Finland, Italy, the Netherlands, Spain, Sweden) and
      Israel, for older people aged 65-89 living both in the community and in
      institutions (total, 11557 subjects). For two age classes (65-74 and 75-84), the
      prevalence ratios or the mean values of the following selected variables are
      provided: a) sociodemographic variables; b) health habits; c) health status; d)
      physical functioning; e) social networks and support; and f) health and social
      services utilization. RESULTS: Statistically significant differences were found
      between most of the investigated characteristics across the CLESA countries, with
      very few exceptions. While some of the differences found may be due to cultural
      variations, others require further investigation and should be encompassed in the
      main framework of the Project, which is to identify predictors of
      hospitalization, mortality, institutionalization and functional decline.
      CONCLUSIONS: A common data base is available for the study of the aging process
      in five European and one Israeli population. These data provide a unique
      opportunity to identify common risk factors for mortality and functional decline
      and increase our understanding of country-specific exposures and vulnerability.

PMID- 14582682
TI  - The Evergreen Project: introduction.

PMID- 14582683
TI  - Reduced mobility and physical activity as predictors of depressive symptoms among
      community-dwelling older adults: an eight-year follow-up study.
AB  - BACKGROUND AND AIMS: Epidemiological research suggests that reduced physical
      activity and mobility may be associated with depressive symptoms. The present
      study examines the relative roles of mobility status and physical activity as
      predictors of depressive symptoms among community-dwelling older adults. METHODS:
      The subjects comprised randomly selected, non-institutionalized residents of the
      city of Jyvaskyla, central Finland, born in 1904-1923. At baseline, 80% (N =
      1224) and after the 8-year follow-up period (1996) 88% (N = 663) of eligible
      persons were interviewed. All non-institutionalized men and women (N = 384) who
      participated in both baseline and follow-up interviews, who supplied data on the
      main questions of interest and who had no depressive symptoms at baseline, were
      selected for analysis. Depressive symptoms were assessed using the Finnish
      modified version of Beck's 13-item depression scale (RBDI). Physical activity was
      assessed on a seven-point scale. Mobility status was defined as the ability to
      walk two kilometers and climb one flight of stairs. RESULTS: Subjects who were
      mobility-disabled and had a sedentary life-style had a higher risk (OR = 2.44)
      for depressive symptoms at follow-up than those who had good mobility and were
      physically active. The risk was also higher (OR = 1.99) in those who were
      mobility-disabled and had a physically active life-style, compared with
      physically active individuals with intact mobility. Those with good mobility had
      fewer depressive symptoms than those who had mobility problems, irrespective of
      the level of physical activity. No significant interaction was observed between
      physical activity and mobility in predicting the development of depressive
      symptoms. Older age significantly increased, and the number of chronic illnesses
      tended to increase the risk of developing depressive symptoms during the follow
      up period. Gender and length of education were not significant predictors of
      depressive symptoms. CONCLUSIONS: Mobility problems and older age seem to
      increase the risk for developing depressive symptoms in elderly people. The risk
      is not associated with the level of physical activity.

PMID- 14582685
TI  - New achievements and pharmacotherapeutic approaches to impotence in the elderly.
AB  - Erectile dysfunction (ED) has a negative impact on the quality of life of elderly
      men, but impotence is not an absolute concomitant of aging. Aging changes
      influencing sexual function in men consist of a decreased capacity to reach
      arousal by imagination or view, fragility of erection, and an increase in the
      refractory period. These events may be part of the andropause syndrome, which
      includes a decrease in intellectual activity, fatigue, depression, decreases in
      body hair, lean body mass and bone mineral density, accompanied by an increase in
      weight. As a consequence, the overlap of aging processes, concurrent diseases and
      social situations to which elderly men are subject, results in the great
      variability reported in epidemiological studies. In the same way, the complex
      physiology of erection depends on the social, environmental, or physical context
      in which it occurs. New achievements in research on intracellular mechanisms of
      erection and on the neuroendocrinology of aging contribute to better
      understanding the pathophysiology of ED in the elderly. For example, testosterone
      declines with age with great interindividual variability, since other hormonal
      changes are also involved. What currently can be easily identified is the
      alteration of LH-testosterone feedback alterations, although hormone levels fall
      in the normal range. Nevertheless, the extent to which age-dependent decline in
      hormones leads to health problems that may affect the quality of life remains to
      be clarified. Several concepts on aging-related processes have been challenged,
      and conditions that were once accepted as physiologically age-related are now
      thought to lead to medical problems, but until now erectile dysfunction remains
      underreported, underdiagnosed, and undertreated, especially in the elderly.
      Nowadays, we are witnessing a rapid growth in available pharmacotherapies, from
      intracavernous injections of vasoactive drugs, to powerful new oral agents, with
      differing pharmacological dynamic and kinetic properties. New options for
      treatment are therefore possible, taking into account both the possibility of
      changing ineffective drugs and augmenting efficacy by means of synergistic
      associations. This rich generation of progress is certainly contributing to a
      better medical approach to sexuality in aging people.

PMID- 14582684
TI  - Multidimensional health assessment of 75- and 80-year-old men and women: a five
      year prospective study.
AB  - BACKGROUND AND AIMS: There are no earlier reports of regular multidimensional
      health check programs in elderly people. The aim of this study was to establish
      the number and type of previously unrecognized health conditions in two cohorts
      of elderly people examined twice during a 5-year period, and to determine how
      these conditions were subsequently evaluated and treated. METHODS: This
      population-based study, carried out at a university research center in Finland,
      consisted of a multidimensional and multiphased health assessment including
      interviews, health questionnaires and medical examinations and tests, and follow
      up of subsequent examinations and treatment. Participants were all 75- (N = 388)
      and 80-year-old (N = 291) people residing in the city of Jyvaskyla in 1989 and
      1990 respectively. RESULTS: A total of 780 health assessments were carried out,
      500 at baseline and 280 five years later. Large numbers of previously
      unrecognized conditions were found on both occasions, ranging from tumors to
      impacted cerumen. At baseline, 180 persons (36% of those assessed) were referred
      for further examinations or treatment, at follow-up 127 (45%). Half of the
      referred persons received treatment, 13-39% were evaluated but not treated. For
      12-33%, no information was obtained on post-hoc events. CONCLUSIONS:
      Comprehensive health assessments in older people reveal a large number of
      previously unrecognized conditions that require further examination and/or
      treatment, suggesting the need for systematic and regular assessments of health
      and functional capacity.

PMID- 14582686
TI  - Unmet home care needs among community-dwelling elderly people in Spain.
AB  - BACKGROUND AND AIMS: Sociodemographic changes affecting the elderly population
      and the family role in providing home care call for reorganization of formal
      community care services. The aim of this study was to determine the prevalence of
      home care needs and the factors associated with unmet home care needs among
      community-dwelling elderly people in Spain. METHODS: The data were derived from a
      representative sample of community-dwelling elderly people living in a town of
      the metropolitan area of Madrid (N = 1135). Dependency for daily, weekly and
      monthly activities was based on disability in activities of daily living (ADL)
      and instrumental activities of daily living (IADL). Insufficient help was
      estimated as an indicator of unmet needs. Logistic regressions were fitted to
      identify correlates of unmet needs for each type of activity. RESULTS: Overall,
      14, 39, and 50% of subjects reported dependency for daily, weekly and monthly
      activities, respectively. Of these, 40, 27, and 12% reported receiving inadequate
      assistance. Unmet needs were strongly associated with low monthly income, low
      educational level, living alone, and symptoms of depression. Families were the
      exclusive source of almost all assistance provided, few persons reporting the use
      of additional formal community care sources. CONCLUSIONS: There are considerable
      social and material inequalities in access to home care. In view of the poor
      coverage of the public system for home and personal care, these inequalities may
      widen in the near future. New public policy initiatives are needed to provide
      affordable formal family-support services.

PMID- 14582687
TI  - Nursing home case-mix instruments: validation of the RUG-III system in Italy.
AB  - BACKGROUND AND AIMS: The current Italian reimbursement system for long-term care
      does not adequately consider the great variability in the health and functional
      status of older persons who are admitted to long-term care institutions.
      Furthermore, no procedure is implemented to monitor the quality of care provided
      to older residents. We conducted this study to verify whether the RUG-III
      (Resource Utilization Groups-version III), a tool for assessing the case-mix of
      nursing home residents, which is widely used in the United States and in many
      European countries, can be effectively used in the Italian health care system.
      METHODS: We administered an Italian version of the RUG-III to 1000 older
      residents of 11 intermediate- and long-term care institutions. We also collected
      objective information on the amount of care provided directly or indirectly to
      each resident by nurses, physical therapists, and other health professionals.
      RESULTS: The RUG-III 44 group classification system explained 61 and 44% of the
      variance in rehabilitative and nursing wage-adjusted care time, respectively.
      CONCLUSIONS: Our findings provide strong evidence that the RUG-III
      classification, applied to Italian intermediate- and long-term care institutions,
      provides a robust estimate of the amount of nursing and rehabilitation resources
      consumed by older residents.

PMID- 14582688
TI  - Effects of influenza vaccination on mortality among frail, community-living
      elderly patients: an observational study.
AB  - BACKGROUND AND AIMS: The annual winter outbreak of influenza is one of the major
      causes of morbidity and mortality among frail elderly people. The aims of the
      present study were to describe the prevalence of vaccination against influenza in
      a population of older people living in the community, and to examine the
      relationship between influenza vaccination and mortality. METHODS: This was an
      observational cohort study. We analyzed data from the Italian Silver Network Home
      Care project, which collected data on patients admitted to home care programs. A
      total of twelve Home Health Agencies participated in this project, evaluating the
      implementation of the Minimum Data Set for Home Care (MDS-HC) instrument. A total
      of 2082 patients were enrolled in the present study. The main outcome measures
      were prevalence of vaccination against influenza and 1-year survival according to
      vaccination status. RESULTS: Nearly half the subjects in our Italian sample did
      not receive influenza vaccination. During a mean follow-up period of 10 months
      from initial MDS-HC assessment, 167 vaccinated subjects (15%) died compared with
      192 non-vaccinated subjects (19%) (p = 0.01). After adjusting for age, gender,
      and all variables significantly different between vaccinated and non-vaccinated
      subjects at baseline (functional and cognitive impairment, number of diseases,
      number of medications, depression, pressure ulcers), vaccinated subjects were
      less likely to die than non-vaccinated ones (RR 0.73; 95% CI 0.56-0.94).
      CONCLUSIONS: Vaccination against influenza has important prognostic implications
      for frail geriatric patients living in the community, independent of age, gender,
      and other clinical and functional variables. Despite extensive scientific
      evidence, recommendations for annual vaccination against influenza among subjects
      at higher risk have never been adequately implemented.

PMID- 14582689
TI  - Monochromatic phototherapy in elderly patients: a new way of treating chronic
      pressure ulcers?
AB  - BACKGROUND AND AIMS: Monochromatic pulsating light may have effects of importance
      for wound healing, and promising results were obtained in an open study on the
      healing of pressure ulcers, which motivated the present study. METHODS: One
      hundred and sixty-four in- and outpatients with grade II and III ulcers were
      treated with monochromatic pulsating light or placebo over the ulcerated area,
      according to a specific therapeutic program. RESULTS: No significant effects were
      observed in the total material. In a subanalysis of grade II ulcers, there was a
      tendency toward better healing in the monochromatic light group (p = 0.06). A
      significantly larger reduction in pressure ulcer size was noted among patients in
      the treatment group with low body weight (BMI < 20). CONCLUSIONS: Monochromatic
      pulsating light may have effects on pressure ulcer healing, and a new study
      focusing only on grade II ulcers is under way.

PMID- 14582690
TI  - Morphological characteristics of skeletal muscles in relation to gender.
AB  - BACKGROUND AND AIMS: The aim of this study was to ascertain whether there are
      gender-related differences in the morphological characteristics of the soleus and
      tibialis anterior muscles in young adult and old Fischer 344/Brown Norway F1
      rats. METHODS: We tested 1) whether there was a gender-related difference between
      the fiber type composition of these muscles, and 2) whether the cross-sectional
      area of individual muscle fibers demonstrated gender-associated differences,
      fibers from males being larger than fibers from females. RESULTS: Gender
      differences were not found in the fiber type composition of the soleus and
      tibialis anterior muscles, but were present in the single skeletal fiber cross
      sectional area of the tibialis anterior muscle. The cross-sectional area of type
      I fibers in females was greater than that in males at both 12 (16%) and 30 (5%)
      months of age. In contrast, the cross-sectional area of type Ila fibers of 12
      month-old males was larger than that of 12-month-old females. No significant
      differences between genders were found for the cross-sectional area of type Ilb
      fibers in either age group. In the soleus muscle, 30-month-old males had larger
      single fiber cross-sectional areas of both fiber types I and lIa. At 12 months of
      age, type I fibers from females were larger than those from males. CONCLUSIONS:
      Our findings indicate that gender-related differences exist in the size of
      individual skeletal fibers from the soleus and tibialis anterior muscles and that
      they may influence metabolism and the adaptive response to rehabilitation
      programs.

PMID- 14582691
TI  - Endocrinocarcinomas (carcinoids and their variants) of the duodenum. An
      evaluation of 927 cases.
AB  - This study was undertaken to supplement our previous analysis of 635 duodenal
      carcinoids to give both wider and different viewpoints on a larger series of
      duodenal endocrinocarcinomas, and to provide up-to-date clinicopathologic
      information regarding these neoplasms. A total of 927 cases of such neoplasms of
      the duodenum were collected from the Niigata Registry for gut-pancreatic
      endocrinomas, consisting of the carcinoid group with 897 cases, 857 typical
      carcinoids and 40 atypical varieties, and the variant group with 30 remaining
      endocrinocarcinomas expressed by various terminology. Significant statistical
      differences between these two groups were evident in various aspects: in sites of
      tumor growth, aggressiveness of invasion to the extra-duodenal structures, rates
      and sites (liver, lymph nodes and bone) of metastases, average tumor-size,
      immunohistochemistry of gastrin and serotonin, rates of recurrence, five-year
      survival rates and others. In addition, a close similarity between these two
      groups was noted in several aspects of histology, histochemistry and
      immunohistochemistry, rendering the variant group in a member of the carcinoid
      family. Regarding the carcinoid group in comparison with that in other organs may
      be summarized as follows: a reasonable male/female ratio of 1.39, a reasonable
      average age of 55.9 years, a high typical/atypical ratio of 21.4, a relatively
      small average tumor-size of 17.7 mm, a relatively low metastasis rate of 27.4%, a
      high histologic B-type dominance of 75.5%, a high postoperative survival rate of
      83.3% and a reasonable incidence of the carcinoid syndrome of 3.1%.

PMID- 14582692
TI  - Retrospective histologic comparison of Helicobacter pylori infection in gastric
      carcinoma, ulcerous disease and non-ulcerous dyspepsia.
AB  - Although a number of epidemiological, biological and clinical studies have been
      published, the effective role of Helicobacter pylori infection in gastric
      carcinogenesis remains unclear. In the present work we retrospectively compared
      Helicobacter infection rate, by means of histologic examination of gastric
      bioptic samples, in 70 patients affected by gastric carcinoma, 70 with ulcerous
      disease and 70 with non-ulcerous dyspepsia. The analysis was carried out by a
      single pathologist. The differences between the 3 groups were not statistically
      significant. From our present and previously reported data, the Helicobacter
      infection cannot be considered per se a significant risk factor for malignant
      gastric disease and further studies are needed to evaluate the role of
      Helicobacter infection in the development of some preneoplastic conditions such
      as chronic atrophic gastritis and intestinal metaplasia.

PMID- 14582693
TI  - Cancer precursor lesions in intact stomach Helicobacter pylori gastritis and in
      resected stomach gastritis.
AB  - Hemigastrectomy for benign disease and Helicobacter pylori infection are risk
      conditions for the development of gastric cancer. Aim of the study was to compare
      gastric histology and precursor lesions of malignancy in these two conditions.
      The hemigastrectomy group included 351 consecutively endoscoped subjects operated
      for gastroduodenal benign disease. Six to ten biopsy specimens were routinely
      taken from the residual gastric mucosa. The intact stomach group included 2097
      consecutively endoscoped symptomatic subjects, who did not receive eradication
      therapy against H. pylori. The histological findings were classified as normal
      mucosa (NM), chronic non atrophic gastritis (CNAG), chronic atrophic gastritis
      (CAG), intestinal metaplasia (IM) and dysplasia (DYS). One thousand and three
      intact stomachs were H. pylori negative, and 1094 showed H. pylori colonization.
      The age over fifty was a significant risk factor for the occurrence of IM (OR
      2.52, P < or = 0.001) and DYS (OR 3.46, P < or = 0.001), while Hp-positivity was
      a risk factor for CNAG (OR 1.81, P < or = 0.001) and CAG (OR 3.88, P < or =
      0.001). Gastroresection was associated to higher risk for CNAG (OR 1.53, P < or =
      0.001) and DYS (OR 4.31, P < or = 0.001) and to a lower risk of CAG (OR 0.49, P <
      or = 0.001). Both in males and females the risk for CNAG was significantly higher
      in Hp-positive (males OR 1.92, P=0.000; females OR 1.70, P=0.000) and
      gastrectomized subjects (males OR 2.06, P=0.000; females OR 2.43, P=0.000).
      Gastrectomized males, furthermore, showed an increased risk for DYS (OR 5.82,
      P=0.000). The aged Hp-negative and Hp-positive subjects evidenced a significant
      risk for IM (respectively OR's 3.42, P=0.000 and 4.85, P=0.000); the risk for DYS
      was significant in aged Hp-negative subjects (OR 4.09 P < or = 0.020). The Hp
      positive individuals evidenced a significant risk for metaplastic mucosal changes
      (OR 38.17, P=0.000). Subjects aged over forty at the time of surgery and those
      with a longer postoperative follow up endoscopy presented an increased risk for
      CNAG of the residual mucosa (respectively OR's 2.75, P=0.000 and 5.25, P=0.000).
      CNAG and IM were the most frequently observed mucosal lesions both in subjects
      operated for duodenal and gastric ulcer (respectively OR's 4.02, P=0.000 and
      3.00, P=0.000). Our data support that hemigastrectomy for benign disease and H.
      pylori infection may induce an increased incidence for histological precursor
      lesions for gastric malignancy and suggest that carcinogenesis in a resected
      stomach may be different from that in the intact stomach.

PMID- 14582694
TI  - Gastrointestinal stromal tumors of the stomach. A ten-year surgical experience.
AB  - Gastrointestinal stromal tumors show an increasing incidence.
      Immunohistochemistry is mandatory to make differential diagnosis with other
      mesenchimal tumors. We retrospectively reviewed 15 primary stomach GISTs operated
      during the last decade. Gastroscopy, Ultrasonography and CT scan were employed to
      obtain the diagnosis. Tumor size ranged from 1.5 to 30 cm in diameter. Treatment
      consisted of curative surgical resection without sistematic lymph node
      dissection. A wedge resection was sufficient in 8 cases. In 2 patients a distal
      subtotal gastrectomy was required and in 1 a total enlarged gastrectomy with
      pancreaticosplenectomy was performed. 4 GISTs were incidentally discovered and
      removed during surgical procedures for other gastrointestinal malignancies. In 4
      cases a laparoscopic wedge resection was possible. In all cases postoperative
      course was uneventful. No adjuvant treatment was administered. Concerning the
      follow-up, two patients died for local and distant relapse while 13 are still
      alive (most of them operated during the last three years). GISTs show a very
      unpredictable clinical course and curative surgery is the only potential
      effective curative treatment.

PMID- 14582695
TI  - The surgeon's decision as a prognostic factor in a pool of patients with
      colorectal cancer coming from different institutions.
AB  - Different pathological and predictive factors are used to stratify patients
      submitted to radical surgery for colorectal carcinoma. In addition to stage and
      histotype, the surgeon's technique and decisions also appeared to affect the
      prognosis. The aim of the present study was to evaluate if the extent of
      lymphadenectomy was associated with a different long-term outcome in a pool of
      117 patients. In particular, in patients classified as Dukes' B, some evidences
      seem to suggest that the staging procedure depends on a correct surgical
      lymphadenectomy with a higher risk of understaging colorectal carcinomas when the
      number of removed nodes is limited. Moreover, the promptness in forwarding
      patients to the chemotherapist seems to influence the disease-free survival.

PMID- 14582696
TI  - Our experience in transrectal ultrasonography and biopsy in carcinoma of the
      prostate.
AB  - The Authors present a short review of the literature comparing transrectal
      ultrasound of the prostate (TRUS) and ultrasound guided biopsy and the results of
      694 consecutive prostatic biopsies from their cohort. All the biopsies were US
      guided with an endorectal biplanar 5 MHz probe and transperineal samples were
      carried out with an 18 G needle (cutting length 22 mm) over the last 4 years. The
      histological exam showed 187 prostates affected by cancer while 112 had only
      inflammation. The operator's opinion, based on ultrasonography and integrated
      with a digital rectal exam (DRE) and a prostate specific antigen (PSA) blood
      test, was correct in 80% of the cases, with 90% sensitivity and 70% specificity.
      The positive prediction rate was 74% and the negative prediction rate was 89%.

PMID- 14582697
TI  - Treatment of glioblastoma multiforme in the elderly in functionally non-critical
      areas. Clinical remarks on 22 patients.
AB  - The aim of this study was to evaluate the efficacy of multimodality treatment of
      glioblastoma multiforme in the elderly. Although several studies report a poor
      outcome in elderly patients with glioblastoma, in the light of our experience,
      treatment of elderly patients with glioblastoma in non-critical areas and
      Karnofsky Performance Status > 60 should be just as aggressive as in younger
      patients.

PMID- 14582698
TI  - Safety and growth suppressive effect of intra-hepatic arterial injection of AdCMV
      p53 combined with CDDP to rat liver metastatic tumors.
AB  - Surgical resection is thought to be the best treatment for liver carcinoma,
      including hepatocellular carcinoma and metastatic liver carcinoma if there are a
      small number of tumors. Liver carcinoma is one of the main causes of death from
      cancer worldwide. The prognosis of liver carcinoma is still poor. Mutation of
      p53, which is well known as a tumor suppressor gene, is observed in many cases of
      advanced liver carcinoma. Cancer gene therapy using p53, which transduces the
      wild-type p53 gene in the tumor, is a promising new strategy for treating liver
      carcinoma. Selective and less invasive gene delivery to the liver tumor is
      necessary for clinical liver tumor gene therapy. The first purpose of the current
      study was to determine the best way to deliver the gene of interest to the liver
      tumor selectively. The second purpose was to study the tumor suppressive effect
      of intrahepatic arterial injection of an adenovirus vector with the p53 gene
      (AdCMV-p53), followed by administration of CDDP and noting its side effects. We
      injected AdCMV-LacZ via hepatic arteries of rats bearing RCN-9 colon cancer
      metastasis in the liver. Injection via the hepatic artery resulted in more
      successful gene transduction to the liver tumor in a tumor-selective manner than
      did injection via the portal vein. At 48 hrs after arterial injection of AdCMV
      p53, CDDP (3 mg/kg) was administered in the peritoneal cavity of each rat. The
      use of CDDP with arterial injection of AdCMV-p53 resulted in more extensive
      apoptosis in the rat liver tumors without any deterioration in liver function. In
      conclusion, hepatic arterial injection of an adenovirus vector is better than
      portal vein injection for gene transduction efficiency, and causes no liver
      function disorder even when the injection is combined with CDDP.

PMID- 14582699
TI  - Amelioration of B16F10 melanoma cells induced oxidative stress in DBA/2 mice by
      pentoxifylline.
AB  - The constantly produced small amounts of reactive oxygen species (ROS) are
      reduced by anti-oxidant enzymes and cellular scavengers. The oxidative stress
      developed by defect in ROS clearance can result in cell injury and may lead to
      carcinogenesis. Pentoxifylline is a methylxanthine derivative with rheologic and
      membrane modifier property. We have examined whether Pentoxifylline (PTX)
      ameliorates oxidative stress produced in subcutaneously injected mice with B16F10
      melanoma cells. Treatment of mice with PTX significantly reduced oxidative stress
      and attenuated the altered changes of reduced glutathione and lipid peroxides.
      Our findings provide an experimental basis for using PTX to attenuate oxidative
      stress induced by B16F10 melanoma cells in liver and lung of DBA/2 mice.

PMID- 14582700
TI  - Evaluation of naphthalmustine, a nitrogen mustard derivative of naphthalimide as
      a rationally-designed anticancer agent.
AB  - Naphthalmustine, 2-[2-[bis-(2-chloroethyl)amino]ethyl]-1H-benz[de]isoquinoline
      1,3-dione (Compound 1) has been synthesized as a rationally designed new
      anticancer agent from N-(2-bromoethyl)naphthalimide. Its chemical alkylating
      activity exceeded that of nor-HN2 used as standard compound for comparison. Its
      antitumour efficacy was assessed in vivo in two murine ascites tumours namely
      Sarcoma-180 (S-180) and Ehrlich ascites carcinoma (EAC) by measuring the increase
      in median survival times (MST) of drug treated (T) over untreated control (C)
      mice. The clinical drug cyclophosphamide and the experimental compound mitonafide
      were used as positive controls for comparison. Compound 1 has displayed
      substantial and reproducible antitumoural activity in these tumours since very
      high remission times of treated animals were observed. Significant increase in
      the life span of mice bearing highly advanced tumour for 10 days before the drug
      challenge was also noted after its treatment. Its LD50 value was 200 mg/Kg by
      single i.p. injection. Its toxicity was also assessed in vivo in normal and in S
      180 bearing mice by measuring drug-induced changes in hematological parameters,
      femoral bone marrow and splenic cellularity sequentially on days 9, 15 and 21
      following drug treatment at the optimum dose of 12 mg/kg from day 1 to 7. The
      results indicated that the compound did not adversely affect hematopoiesis. Drug
      induced hepatotoxicity and nephrotoxicity were also evaluated on those days but
      no such toxicities were detected. Naphthalmustine inhibits the synthesis of DNA
      and RNA in S-180 tumour cells. It was further screened in vitro in 4 different
      human tumour cell lines but no significant activity was observed in those lines.

PMID- 14582701
TI  - Effect of naturally occurring monoterpenes carvone, limonene and perillic acid in
      the inhibition of experimental lung metastasis induced by B16F-10 melanoma cells.
AB  - The effects of naturally occurring monoterpenes on lung metastasis induced by
      B16F-10 melanoma cells were studied in C57BL/6 mice. Administration of
      monoterpenes such as limonene (100 micromoles/kg body wt. 10 doses i.p.) and
      perillic acid (50 micromoles/kg body wt 10 doses i.p.) remarkably reduced the
      metastatic tumour nodule formation by 65% and 67%, respectively. These results
      correlated with the biochemical parameters such as serum sialic acid, lung
      collagen hydroxyproline and uronic acid contents. Serum sialic acid level in
      control group was 126.8 microg/ml serum which was significantly lowered in
      limonene (49.3 microg/ml serum) and perillic acid treated animals (53.6 microg/ml
      serum). Uronic acid level was also inhibited to 56% and 39.7% in limonene and
      perillic acid treated animals, respectively. Histopathological studies also
      correlated with these above results. Administration of Carvone even at 100
      micromoles/kg body wt. did not have any significant effect on the metastatic
      tumour growth. These results indicate that limonene and perillic acid could
      inhibit the metastatic progression of B16F-10 melanoma cells in mice.

PMID- 14582703
TI  - Expressions of Lewis antigens in human non-small cell pulmonary cancer and
      primary liver cancer with different pathological conditions.
AB  - The expressions of three X series Lewis antigens, including Lewis X (Le(x)),
      sialyl Lewis X (SLe(x)) and sialyl dimeric Lewis X (SDLe(x)) were studied with
      immuno-histochemical methods in human non-small cell pulmonary cancer (NSCPC) and
      primary liver cancer (PLC) with different pathological conditions. The Lewis
      antigens are mainly expressed on the cell surfaces, medially or slightly in the
      cytoplasm, but not in the cell nuclei of the cancer tissues. The regions adjacent
      to the cancer tissues do not express any Lewis antigens. The positive rates of
      these antigens in NSCPC were within the range of 75% to approximately 86%. There
      was no apparent difference in positive rates between the cases with different
      differentiation and the presence or absence of metastasis in peripheral lymph
      nodes, nor among the three antigens, except that the positive rate of SDLe(x) was
      lower (about 56%) in the cases with well/medium differentiation and without
      metastasis. However, the expression-intensities (SI indexes) of all three
      antigens were significantly higher in the samples of poor differentiation and
      with metastasis as compared to those with well/medium differentiation and without
      metastasis. The two sialyl Lewis antigens increased more significantly than non
      sialylated Le(x). The expressions of these antigens were also observed in the
      peripheral lymph nodes with metastasis, but not in those without metastasis. The
      positive rates of Le(x), SLe(x) and SDLe(x) in human primary liver cancer were
      83.3%, 88.9% and 77.8%, respectively. In the cases with cancer cell thrombosis
      (CCT) in portal vein (an index of metastasis), the expressions of all these three
      antigens were stronger than those in the cases without CCT. SLe(x) was the most
      abundant and most highly increased Lewis antigen on the surface of NSCPC and PLC,
      especially in the cases with poor differentiation and metastasis. In the study of
      the enzymatic basis of the increased Lewis antigens in PLC by using Northern
      blot, it was found that the level of alpha1,3 FucT-III/VI mRNA in PLC tissues was
      much higher than that in the adjacent regions, and more significantly higher in
      the cancer tissues from patients with CCT in portal vein. In contrast, the
      expression of alpha1,3 FucT-VII was rather low in cancer tissues and not
      different from the adjacent regions in spite of the presence or absence of CCT.
      These results reveal that the SLe(x) in PLC is mainly synthesized by alpha1,3
      FucT-III/VI (especially VI) and is the most important Lewis antigen involved in
      the metastasis of PLC.

PMID- 14582702
TI  - Expression of cyclooxygenase-2 in human hyperplastic gastric polyps.
AB  - Cyclooxygenase (COX)-2, an inducible isoform of prostaglandin synthetase, has
      been reported to be a key molecular target of colon cancer prevention by
      nonsteroidal anti-inflammatory drugs. Recently, it has been shown that
      Helicobacter pylori (H. pylori) could induce COX-2 together with inflammatory
      cytokines. Although human hyperplastic gastric polyps disappeared or decreased in
      number and size after eradication of H. pylori, the mechanisms in this step,
      especially the roles of COX-2, have not been yet elucidated. The aims of the
      present study were to examine the expression and localization of COX-2 in human
      hyperplastic gastric polyps immunohistochemically. Twelve specimens of human
      hyperplastic gastric polyps were obtained from endoscopic polypectomy. The
      expression of the COX-2 protein was immunohistochemically examined on formalin
      fixed and paraffin-embedded tissue sections using an anti-COX-2 antibody and an
      avidin-biotin complex method. Cells expressing COX-2 were further
      immunohistochemically identified using a specific antibody against macrophages
      (CD68), and myofibroblasts (alpha-smooth muscle actin). Immunoreactive COX-2 was
      predominantly and strongly expressed in interstitial cells in the sub-epithelial
      layer of 10 hyperplastic polyps. Semi-quantitative analysis revealed a
      significant increase in COX-2 expression in interstitial cells. The staining
      pattern of macrophages and myofibroblasts partly corresponded to that observed
      for COX-2 in hyperplastic gastric polyps. These results suggest that COX-2 in
      mesenchymal cells induced by H. pylori may play an important role in the
      tumorigenesis of human hyperplastic gastric polyps.

PMID- 14582704
TI  - 34-BetaE12 expression in benign and premalignant squamous lesions of skin:
      relation to cell proliferation (Ki-67).
AB  - The antibody 34-betaE12 stains selectively the keratins of basal cells. The aim
      of this study is to investigate the staining pattern of 34-betaE12 in borderline
      (keratoacanthomas and solar keratosis), and benign lesions (seborrheic
      keratoses). The proliferation index Ki-67 staining was also evaluated in these
      and also in malignant (basal and squamous cell carcinomas) cases. The staining
      pattern where the 34-betaE12 positive cells found in the basal, suprabasal
      epidermal layers was called "focal"; and the staining in all layers including
      upper spinous layer was called "diffuse". Mean proliferation index and the
      distribution pattern of Ki-67 immunohistochemical expression were assessed. Basal
      and suprabasal expression of 34-betaE12 significantly predominated in the normal
      parts of the epidermis, in eight out of 11 seborrheic keratoses (%73), one out of
      the 19 keratoacanthomas (%5), two out of 11 solar keratosis (18%). Statistical
      analysis revealed significant differences between mean level of Ki-67 expression
      of malignant (squamous cell carcinoma, basal cell carcinoma), benign (seborrheic
      keratoses) and premalignant (solar keratoses, keratoacanthomas) lesions (p<0.01).
      The distribution of staining pattern for Ki-67 paralleled to the staining pattern
      of 34-betaE12. Basal cell status assessment completed by 34-betaE12 may resolve
      some, but not all of the problems in terms of determining the presence of
      dysplasia.

PMID- 14582705
TI  - p53 expression in oral cancer: observations of a South Indian study.
AB  - Oral cancers constitute a significant proportion of hospital admissions among
      cancer patients in India. The aim of this study was to elucidate the role of
      tumour suppressor gene p53 in the pathogenesis of oral squamous cell carcinoma by
      immunohistochemistry. Though extensive studies on p53 alterations in oral cancers
      have been done in Western countries and some Asian countries, only a few studies
      have emerged from India, especially the Southern states. This study would
      therefore be helpful in providing an Indian perspective, with particular
      reference to South Indian states. A total of 110 cases of oral squamous cell
      carcinoma, 35 dysplastic lesions, 15 hyperplastic lesions, and 50 samples of
      normal mucosa were assessed for p53 expression. Out of 110 cases of oral
      carcinoma, 40 (36%) were p53 positive. Among 35 cases of dysplastic lesions
      studied, 6 (17%) showed p53 positive staining. None of the hyperplastic lesions
      and normal oral lesions showed any evidence of p53 positivity. However, in 9 out
      of 40 (23%) cases of positive infiltrating squamous cell carcinomas, the adjacent
      or overlying non-tumourous epithelium demonstrated focal areas of p53 positive
      staining in the basal and parabasal layers of the epithelium. In addition, in 7
      out of 110 (6%) cases, cytoplasmic staining was observed. In these samples,
      nuclei were not stained. Our results indicate that p53 over-expression may be
      involved in only a certain proportion of oral carcinomas. The fact that 6% of the
      dysplastic lesions were p53 positive, and adjacent non-tumourous epithelium of
      23% infiltrating squamous cell carcinomas showed positive staining for p53 in the
      progenitor compartment of the epithelium indicates that p53 immunoreactivity
      could be used to detect early tumours as well.

PMID- 14582706
TI  - Beta-chemokine, macrophage inflammatory protein-1beta (MIP-1beta), is highly
      expressed in diffuse type human gastric cancers.
AB  - Chemokines have been shown to be expressed in some malignant or precancerous
      tissues. However, the role of these chemokines on tumor development or
      progression is not clear. The expression patterns of chemokines in gastric cancer
      tissues were examined in 86 surgically resected samples using
      immunohistochemistry. Macrophage inflammatory protein-1beta (MIP-1beta) was
      clearly detected in many gastric carcinoma cells. In most of the differentiated
      carcinomas, intracellular localization of MIP-1beta was detected in more than 5%
      of cancer cells, although the percentages of MIP-1beta-positive cells differed
      among each sample. Undifferentiated carcinomas showed contrasted staining pattern
      between solid type and non-solid (diffuse) type. MIP-1beta was totally absent in
      all the poorly differentiated carcinomas with solid type growth pattern (por1).
      In contrast, MIP-1beta was highly expressed in all of the non-solid type of
      poorly differentiated carcinoma (por2) and signet-ring cell carcinoma samples. In
      particular, MIP-1beta was strongly stained in carcinoma cells at the front of
      invasive lesions. In 43 diffuse type undifferentiated cancers, tumors with high
      expression of MIP-1beta exhibited significantly more lymph node metastasis. Our
      results suggest a possibility that MIP-1beta may be related to the scattering and
      invasion step of gastric carcinoma cells with undifferentiated phenotype.

PMID- 14582707
TI  - A study on angiogenesis-related matrix metalloproteinase networks in primary
      hepatocellular carcinoma.
AB  - Matrix metalloproteinases (MMPs) specially degrade extracellular matrix (ECM)
      proteins and are involved in tissue remodeling and angiogenesis. Therefore,
      studies on the role of MMPs in the carcinogenesis, proliferation and infiltration
      of hepatocellular carcinoma (HCC) may greatly contribute to the development of a
      new clinically applicable therapeutic approach. In the present study, we
      immunologically examined the expression rates of various MMPs including MMP-2, 3,
      7, 9, membrane type 1-MMP (MT1-MMP), and MT2-MMP in the cancerous and
      noncancerous areas of resected tumor specimens from 30 patients with primary HCC.
      The rate of MMP-2 expression was high for both cancerous and noncancerous areas.
      However, the expression rates of MMP-3, MT1-MMP, and MT2-MMP were significantly
      higher in cancerous areas than in noncancerous areas. Next, we examined the
      clinicopathologic features such as the number of tumor nodules, maximal tumor
      size, presence or absence of capsular infiltration and portal vein invasion,
      histological grades of HCCs, state of noncancerous areas (chronic hepatitis: CH
      or liver cirrhosis: LC), and short-term recurrence after resection (within six
      months). In conclusion, it was found that three main networks of MMPs are
      predominantly involved in the case of HCC, that is, MMP-2 and MT1-MMP in the
      carcinogenesis and progression, MMP-7 and MMP-9 in the capsular infiltration and
      portal vein invasion, as well as MMP-3 and MMP-7 in the progression of HCC.
      Furthermore, MT1-MMP appeared to be the most important factor in HCC because of
      its widespread pattern of expression.

PMID- 14582708
TI  - Down-regulation of ID2 by all-trans retinoic acid in monocytic leukemia cells
      (THP-1).
AB  - Accumulated evidence supports that both Id helix-loop-helix proteins and
      derivatives of vitamin A, retinoids, play a pivotal role in the regulation of
      cell growth and differentiation. We analyzed the effects of all-trans retinoic
      acid (atRA) on the gene and protein expression of Id2 in THP-1 cells and found a
      suppression of the levels of Id2. The down-regulation was abolished towards a
      constitutively expressed level of Id2 mRNA. The decreased level of Id2 was
      associated with growth suppression and does support the prevalent conception of
      the action of Id2 as a stimulator of cell growth.

PMID- 14582709
TI  - Effect of ets-related transcription factor (ERT) on transforming growth factor
      (TGF)-beta type II receptor gene expression in human cancer cell lines.
AB  - Transcriptional repression of the TGF-beta type II receptor (RII) is one of the
      mechanisms leading to TGF-beta resistance. The newly identified epithelium
      specific ets transcription factor ERT/ESX/ESE-1 binds to the TGF-beta RII
      promoter and induces promoter activity. This study aims to investigate the
      mechanisms underlying development of ERT-mediated TGF-beta resistance using
      antisense ERT oligonucleotide. We performed Northern blot analysis of TGF-beta
      RII expression in human colon cancer cell line, RKO, after transfecting these
      cells with MFG-antisense-ERT retroviral construct. The plasmid containing the
      chloramphenicol acetyltransferase (CAT) gene alone was used as the control. The
      amount of TGF-beta RII mRNA appears to be poor in RKO cells expressing antisense
      ERT compared with both parental RKO and control cells. In conclusion,
      transfection of MFG-antisense-ERT construct into the colon cancer cell line could
      result in lower levels of TGF-beta RII mRNA expression, which means that ERT
      mediates the expression of TGF-beta RII and the transcriptional inhibition of ERT
      could be a one of the mechanisms of colonic carcinogenesis. More in vitro and in
      vivo studies should be required to evaluate this treatment in clinical setting.

PMID- 14582710
TI  - Clinically meaningful response to the EGFR tyrosine kinase inhibitor gefitinib
      ('Iressa', ZD1839) in non small cell lung cancer.
AB  - Preclinical research and ongoing clinical trials are validating epidermal growth
      factor receptor (EGFR) as a suitable molecular target in cancer therapy. Here we
      report the case of a 39-year-old non-smoking man with heavily pretreated stage IV
      bronchioloalveolar NSCLC who was treated with gefitinib ('Iressa', ZD1839) at the
      dose of 250 mg/day, orally. Symptomatic relief was already detectable after 2
      weeks of gefitinib therapy, pulmonary function tests readily improved,
      performance status went from 2 to 0 within 8 weeks, CT scan performed after 10
      weeks of treatment showed nearly complete resolution of the clinical picture, and
      clinical remission was maintained up to 32 weeks. This case-report illustrates
      the potential of EGFR tyrosine kinase inhibition to induce clinically meaningful
      responses in heavily pretreated, advanced NSCLC patients and suggests that
      participation of such patients into clinical trials of signal transduction
      inhibitors should be encouraged.

PMID- 14582711
TI  - The cytogenetic investigation on peripheral blood lymphocytes of a patient with
      thyroid cancer.
AB  - The cytogenetic investigation of a patient with follicular cancer in the left
      lobe of the thyroid gland was made. The study was carried out on blood
      lymphocytes as described earlier (1) before and after hemithyroidectomy and in
      different terms during the therapeutic treatment. The great number of cells with
      polyploid and hyperaneuploid (13% and 5% correspondingly) were revealed in the
      patient on the day before the operation and confirmed malignant character of the
      tumour, which was confirmed histologically. It is believed that cytogenetic
      markers as trisomies 4-th chromosome or/and X chromosome, detected in
      hyperaneuploids cells before the beginning of a treatment, might be specific
      markers for follicular thyroid cancer (FTC). The cytogenetic examination of the
      patient, carried out on peripheral blood lymphocytes in dynamics, allowed to
      observe changes of background chromosomal breaches under influence of surgical
      and therapeutic treatment and to estimate their efficiency.

PMID- 14582712
TI  - A case of long surviving metastatic retroperitoneal epithelioid sarcoma in a 20
      year old male.
AB  - This is the case of a 20 year-old male who came to our observation with a
      neoplastic lesion of the retroperitoneum. At diagnosis it had already spread to
      the lung, the liver and to the retroperitoneal para aortic lymph nodes. The
      patient was treated only with chemotherapy, first 4 cycles of PEI schedules and
      the second option were 3 cycles of EI schedule. After the first treatment the
      disease showed the enlargement of a liver lesion, in the VII segment and the
      vascular component of it was increased. This same lesion, after the EI
      administration, colliquated and didn't modify its size. Since the end of the
      therapy the patient has been followed up every 3 months for the first 3 years and
      every 6 months from the third year onward; he is now at 5 years from the last
      treatment with a stable disease.

PMID- 14582713
TI  - Clinically silent Paget disease of male nipple.
AB  - Male breast cancer constitutes less than 1% of all breast cancer cases. Special
      types, such as Paget disease of the breast, are extremely rare. To our knowledge
      there are less than 50 cases of Paget disease of male breast described in world
      medical literature. Authors present pathologically proven but clinically silent
      case of Paget disease of the nipple in an 86-year old male with breast cancer.
      Literature data suggest that the prognosis of male Paget cancer is worse than in
      "ordinary" male breast cancer. Therefore, the histologic diagnosis of Paget
      disease, even in an asymptomatic male patient, may have negative prognostic
      value.

PMID- 14582714
TI  - Metachronous muscle metastases as a unique manifestation of colon cancer relapse.

PMID- 14582715
TI  - Invited editorial: a whether forecast.

PMID- 14582716
TI  - The evolution of the international system of radiological protection: food for
      thought from the Nuclear Energy Agency Committee on Radiation Protection and
      Public Health.
AB  - From its inception, the Nuclear Energy Agency (NEA), which is part of the broader
      Organisation for Economic Co-operation and Development, has contributed to the
      development of international radiological protection norms and standards. This
      continues today, in the form of studies and workshops to assist radiological
      protection policy makers, regulators and practitioners to develop concepts and
      approaches to help the international system of radiological protection, as
      recommended by the International Commission on Radiological Protection (ICRP), to
      evolve to better serve societal needs. The NEA's Committee on Radiation
      Protection and Public Health (CRPPH), in providing this support, has collaborated
      closely with the ICRP and strongly supports the current ICRP recommendation
      development process. In particular, active dialogue with a broad range of
      stakeholders is contributing to the evolution of concepts towards consensus on
      new ICRP recommendations. The CRPPH, as a body of ICRP recommendation
      practitioners, feels that the public, workers and the environment are well
      protected by the current radiological protection system, but agrees that a new
      consolidation and clarification of ICRP recommendations would be of value. The
      intent of the CRPPH in collaborating with ICRP is to develop a system of
      radiological protection that is simplified, more coherent, firmly based upon
      science and more clearly presented than the current system. This paper summarises
      the more detailed views of the CRPPH on the evolution of the system of
      radiological protection.

PMID- 14582717
TI  - Cancer mortality in a Texas county with prior uranium mining and milling
      activities, 1950-2001.
AB  - Uranium was discovered in Karnes County, Texas, in 1954 and the first uranium
      mill began operating in 1961 near Falls City. Uranium milling and surface and in
      situ mining continued in Karnes County until the early 1990s. Remediation of
      uranium tailings ponds was completed in the 1990s. There were three mills and
      over 40 mines operating in Karnes County over these years and potential exposure
      to the population was from possible environmental releases into the air and
      ground water. From time to time concerns have been raised in Karnes County about
      potential increased cancer risk from these uranium mining and milling activities.
      To evaluate the possibility of increased cancer deaths associated with these
      uranium operations, a mortality survey was conducted. The numbers and rates of
      cancer deaths were determined for Karnes County and for comparison for four
      'control' counties in the same region with similar age, race, urbanisation and
      socioeconomic distributions reported in the 1990 US Census. Comparisons were also
      made with US and Texas general population rates. Following similar methods to
      those used by the National Cancer Institute, standardised mortality ratios (SMRs)
      were computed as the ratio of observed numbers of cancers in the study and
      control counties compared to the expected number derived from general population
      rates for the United States. Relative risks (RRs) were computed as the ratios of
      the SMRs for the study and the control counties. Overall, 1223 cancer deaths
      occurred in the population residing in Karnes County from 1950 to 2001 compared
      with 1392 expected based on general population rates for the US. There were 3857
      cancer deaths in the four control counties during the same 52 year period
      compared with 4389 expected. There was no difference between the total cancer
      mortality rates in Karnes County and those in the control counties (RR = 1.0; 95%
      confidence interval 0.9-1.1). There were no significant increases in Karnes
      County for any cancer when comparisons were made with either the US population,
      the State of Texas or the control counties. In particular, deaths due to cancers
      of the lung, bone, liver and kidney were not more frequent in Karnes County than
      in the control counties. These are the cancers of a priori interest given that
      uranium might be expected to concentrate more in these tissues than in others.
      Further, any radium intake would deposit primarily in the bone and radon progeny
      primarily in the lung. Deaths from all cancers combined also were not increased
      in Karnes County and the RRs of cancer mortality in Karnes County before and in
      the early years of operations (1950-64), shortly after the uranium activities
      began (1965-79) and in two later time periods (1980-89, 1990-2001) were similar,
      1.0, 0.9, 1.1 and 1.0, respectively. No unusual patterns of cancer mortality
      could be seen in Karnes County over a period of 50 years, suggesting that the
      uranium mining and milling operations had not increased cancer rates among
      residents.

PMID- 14582718
TI  - The LNT model is the best we can do--today.
AB  - The form of the dose-response curve for radiation-induced cancers, particularly
      at low doses, is the subject of an ongoing and spirited debate. The present
      review describes the current database and basis for establishing a low dose,
      linear no threshold (LNT) model. The requirement for a dose-response model to be
      used for risk assessment purposes is that it fits the great majority of data
      derived from epidemiological and experimental tumour studies. Such is the case
      for the LNT model as opposed to other nonlinear models. This view is supported by
      data developed for radiation-induced mutations and chromosome aberrations.
      Potential modifiers of low dose cellular responses to radiation (such as adaptive
      response, bystander effects and genomic instability) have not been shown to be
      associated with tumour development. Such modifiers tend to influence the slope of
      the dose-response curve for cellular responses at low doses and not the shape-
      thereby resulting in a quantitative modification rather than a qualitative one.
      Additional data pertinent to addressing the shape of the tumour dose-response
      relationship at low doses are needed.

PMID- 14582719
TI  - Stable chromosome aberration frequencies in men occupationally exposed to
      radiation.
AB  - The introduction of fluorescence in situ hybridisation techniques to cytogenetic
      biodosimetry has enabled the detection of stable aberrations, e.g.
      translocations, which can provide an integrated measure of radiation exposure.
      The opportunity to study stable aberration frequencies in lymphocyte cultures
      from occupationally exposed workers with well-documented dosimetry records
      enables the establishment of dose-response relationships which can be compared
      with those obtained from studies of populations with high acute exposures. Since
      there is good mechanistic evidence for the role of translocations in oncogenesis,
      this provides an insight into the risks associated with low-dose exposure for
      which no direct epidemiological evidence is available. This paper provides
      preliminary data on a group of 98 individuals with cumulative occupational doses
      > 500 mSv and 96 controls with doses < 50 mSv. An increased frequency of
      translocations was found for the high-dose group (20.50 +/- 0.78 x 10(-3) per
      genome equivalent) in comparison with the control group (11.71 +/- 0.59 x 10(-3)
      per genome equivalent). Further analysis of the control group revealed increasing
      frequencies of translocations with increasing age. An increase associated with
      ever-smoking status was found for the control group which appeared to be driven
      by the lower age groups but no overall effect of smoking was seen in the > 500
      mSv group.

PMID- 14582720
TI  - A method for assessing occupational exposure to power-frequency magnetic fields
      for electricity generation and transmission workers.
AB  - A new method for assessing both current and historical occupational exposures to
      magnetic fields has been developed and used in health studies involving a cohort
      of electricity generation and transmission workers in England and Wales. The
      exposure values are derived by calculation from engineering and operational data
      about the power stations rather than from measurements. They are provided for
      each of 11 job categories for each year of operation of each power station
      represented in the cohort. The engineering data are used to determine the average
      magnetic fields in specified areas of work within the power station and then
      applied to information about the time spent in these areas by each of the job
      categories. The operational data are used to adjust the exposures for each year
      according to the power station output for the year. Earlier methods used
      measurements or the advice of panels of experts to provide exposure scores for a
      number of job categories across all power stations and years. Such methods were
      not able to distinguish exposures from different power facilities or during the
      different years of their operation. Measurement surveys at 10 power stations of
      the magnetic fields in the work areas gave confidence that the calculations were
      realistic. Exposure measurements on 215 workers at three power stations were
      compared in job groups with the exposures predicted by the method. The Pearson
      correlation coefficient was 0.86 and the slope and intercept of the line of best
      fit were 0.87 and 0.07 microT respectively. The method gives a good prediction of
      measured exposure and is being used for studies of occupational exposure to
      magnetic fields and leukaemia, and of cardiovascular disease, and a reanalysis of
      brain cancer.

PMID- 14582721
TI  - Radiation risk in the context of liability for injury.
AB  - It is perceived by the man in the street that low-level radiation from a nuclear
      facility is more dangerous than that from other practices. The radiation
      protection system, in particular the ALARA principle, leads to concerns that even
      the smallest exposure to radiation is abnormal and dangerous. Public perception
      of the radiation risk leads to fear in the minds of the public. A consequence of
      this fear itself may be damage to health in the form of psychological damage or
      nervous shock. The paper draws attention to the liability for damages by
      radiation, in particular under the common law of the UK and US, and how
      liability, determined by the court, is not necessarily influenced by scientific
      rationality. A natural conclusion may be that a claimant suffering injury of the
      type caused by radiation and who had been exposed to radiation, no matter how
      small a dose, that could be shown to come from a nuclear installation would be
      awarded damages against the licensee of the site of the installation unless it
      could be shown that the injury was predominantly caused by another source
      (radioactive or otherwise).

PMID- 14582723
TI  - Evaluation of radiation risk and work practices during cerebral interventions.
AB  - This study was intended to evaluate radiation risk to patients during cerebral
      interventions and the contribution to this risk from work practices. Thirty nine
      patients undergoing cerebral interventions in a digital subtraction angiography
      suite were included in this study. Patients who underwent cerebral interventions
      were categorised into two groups according to the number of cerebral
      interventions performed on them, and their effective doses were calculated. The
      effective dose for patients undergoing a single cerebral intervention (group A)
      varied from 1.55 to 15.9 mSv and for multiple cerebral interventions (group B)
      varied from 16.52 to 43.52 mSv. Two patients who underwent multiple cerebral
      interventions (group B) had alopecia of the irradiated scalp.

PMID- 14582722
TI  - An effective and better strategy for reducing body burden of radiostrontium.
AB  - In this study we have examined the effect of different calcium salts, Ca
      gluconate (CaG), Ca lactate (CaL), Ca carbonate (CaC) and Ca phosphate (CaP), on
      the clearance of radiostrontium (*Sr) administered either intraperitoneally (ip)
      (*Sr-ip group) or orally (*Sr-oral group) in rats. The influence of these Ca
      salts was examined in a group of animals administered *Sr ip, while the effect of
      three Ca salts (CaG, CaL and CaP) was studied in another group of rats given *Sr
      orally and compared with that of Ca alginate (CaA), normally advised for *Sr
      decorporation. Rats from both groups were subdivided into control and four
      experimental subgroups and were housed individually. The experimental subgroups
      were given the respective Ca salts (elemental Ca = 9 mg/rat/day) 2 h post 85Sr,
      and thereafter once daily. In the *Sr-ip group, CaG was administered ip while the
      other Ca salts were given orally. In the *Sr-oral group all Ca salts were
      administered orally. In addition, the diet of all the experimental subgroups was
      supplemented with the respective Ca salts to 2% elemental Ca. The whole-body
      retention (WBR) of *Sr in animals treated with Ca salts was found to be
      significantly reduced from 50-60% at 24 h to 20-30% at the end of 15 days
      compared with 70-80% at 24 h to 50-60% at the end of 15 days in the untreated
      control animals. The results strongly suggest that CaA could be replaced by any
      of the commonly used Ca salts for curtailing the WBR of *Sr. CaG which was
      administered ip, in the *Sr-ip group, was found to be more effective in reducing
      the WBR of *Sr.

PMID- 14582724
TI  - International radiation safety standards.
AB  - The system of international safety standards of the International Atomic Energy
      Agency (IAEA) is described with explanations as to the purpose of each level of
      the hierarchy. There is a system of committees that advise the IAEA and approve
      the safety standards and one of these committees is the Radiation Safety
      Standards Committee (RASSC). The Committee meets twice a year (the last meeting
      was 24-27 March 2003) and this note outlines the current situation with respect
      to published safety standards documents at the fundamentals, requirements and
      guides levels and the status of documents under development. Guidance on how to
      find more information and to keep up to date on the development of documents is
      provided. The forward plans of the IAEA in this area are discussed briefly.

PMID- 14582725
TI  - Update on Irish Government's objections to UK nuclear activities.

PMID- 14582727
TI  - DEFRA launches its consultation on a new Veterinary Surgeons Act.

PMID- 14582726
TI  - New study on leukaemia and malignant lymphoma in the vicinity of the Kruemmel
      power plant in northern Germany.

PMID- 14582728
TI  - What is a profession--and who should regulate it?

PMID- 14582729
TI  - Adding up the costs of a veterinary education.

PMID- 14582731
TI  - Correlation of urinary nitric oxide concentrations with the development of hip
      dysplasia in Labrador retrievers.
AB  - Urinary nitric oxide was determined in terms of the ratio of the concentrations
      of total urinary nitrite and nitrate:creatinine in 40 juvenile labrador
      retrievers, and radiographic signs of hip dysplasia and distraction indices were
      investigated in the same dogs in later life. The ratio was correlated
      significantly with the Norberg angle and with subchondral sclerosis in both hips,
      and with the grade of dysplasia in each hip and the dogs' overall grade of hip
      dysplasia. No correlations were observed between the ratio and the distraction
      indices or other radiographic criteria for hip dysplasia.

PMID- 14582730
TI  - Outbreak of equine herpesvirus type 1 myeloencephalitis: new insights from virus
      identification by PCR and the application of an EHV-1-specific antibody detection
      ELISA.
AB  - Five of 10 pregnant, lactating mares, each with a foal at foot, developed
      neurological disease. Three of them became recumbent, developed complications and
      were euthanased; of the two that survived, one aborted an equine herpesvirus type
      1 (EHV-1)-positive fetus 68 days after the first signs were observed in the index
      case and the other gave birth to a healthy foal on day 283 but remained ataxic
      and incontinent. The diagnosis of EHV-1 myeloencephalitis was supported by
      postmortem findings, PCR identification of the virus and by serological tests
      with an EHV-1-specific ELISA. At the time of the index case, the 10 foals all had
      a heavy mucopurulent nasal discharge, and PCR and the ELISA were used to detect
      and monitor EHV-1 infection in them. The status of EHV-1 infection in the five in
      contact mares was similarly monitored. Sera from three of the affected mares,
      taken seven days after the index case were negative or had borderline EHV-1
      specific antibody titres. In later serum samples there was an increase in the
      titres of EHV-1-specific antibody in two of the affected mares. In contrast, sera
      from the five unaffected in-contact mares were all EHV-1-antibody positive when
      they were first tested seven or 13 days after the index case.

PMID- 14582732
TI  - Antibiotic susceptibilities of recent isolates of Mycoplasma bovis in Belgium.
AB  - The susceptibilities of 40 recent Belgian field isolates of Mycoplasma bovis to
      10 antimicrobial agents were assessed. Tiamulin was the most active antimicrobial
      agent against M bovis, with an initial inhibitory concentration (IIC50) of 0.06
      microg/ml, but it is not licensed for the treatment of cattle. All three
      fluoroquinolones tested (danofloxacin, enrofloxacin and marbofloxacin) were
      effective against strains of M bovis, and had a minimum mycoplasmacidal
      concentration (MMC50) less than or equal to 1 microg/ml. Gentamicin was poorly
      effective, having an IIC50 of 8 microg/ml. Many strains of M bovis were resistant
      to tylosin, spectinomycin, lincomycin, tetracycline and oxytetracycline.

PMID- 14582733
TI  - Relationship between the severity of porcine proliferative enteropathy and the
      infectious dose of Lawsonia intracellularis.

PMID- 14582734
TI  - Cloacal prolapse in ostrich chicks with histomoniosis.

PMID- 14582735
TI  - Treatment of a cystic nasal concha in a yearling bull.

PMID- 14582736
TI  - Scottish sheep scab initiative.

PMID- 14582737
TI  - Poor reproductive performance in pigs.

PMID- 14582739
TI  - Administration of identification boluses to sheep.

PMID- 14582738
TI  - Investigation of pimobendan versus benazepril in canine myxomatous valvular
      disease.

PMID- 14582740
TI  - Need for clinical audit.

PMID- 14582741
TI  - 55 kb plasmid and virulence-associated genes are positively correlated with
      Salmonella enteritidis pathogenicity in mice and chickens.
AB  - Twenty-four strains of Salmonella enteritidis, isolated from several outbreaks of
      salmonellosis from different poultry farms in India, were checked for the plasmid
      profile and detection of virulence gene(s) by PCR. Most of the strains contained
      only a single plasmid of 55 kb. Additional plasmids of 23.2 kb and 8.7 kb were
      seen in one of the strains, and another strain carried only two plasmids of 23.2
      kb and 8.7 kb. Four strains did not carry any plasmid. PCR amplification showed
      the presence of virulence-associated genes in all the isolates harbouring the 55
      kb plasmid. Intraperitoneal inoculation of mice, with most of the strains
      carrying the 55 kb plasmid, caused 100% mortality. Most strains lacking the 55 kb
      plasmid were avirulent. In chickens, oral inoculation of the S. enteritidis
      strains carrying the 55 kb plasmid produced 40-100% mortality, with
      characteristic signs of salmonellosis. Oral inoculation of strains lacking the 55
      kb plasmid did not cause any mortality. Hence, it appears that the large plasmid
      of S. enteritidis probably contributes towards virulence in mice and chickens.

PMID- 14582742
TI  - The efficacy of a bivalent vaccine against pasteurellosis and rabbit haemorrhagic
      disease virus.
AB  - Rabbit haemorrhagic disease virus (RHDV) and Pasteurella multocida bacteria cause
      severe losses among rabbit populations. The efficacy of a recently developed
      bivalent vaccine against pasteurellosis and RHDV was investigated. Doses
      exceeding 2 haemagglutinating units (HU) of viral antigen were sufficient to
      protect rabbits against infection with RHDV. The bivalent vaccine appeared to be
      safe for use in all age groups of rabbits, including pregnant females, even after
      treatment with 20 times the normal vaccine dose. Rabbits injected with 8 or 4 HU
      of bivalent vaccine showed high antibody titres against both organisms for 9
      months after inoculation. The antibody levels against RHDV in young rabbits at 30
      days of age were elevated when they originated from mothers with high antibody
      titres. The most suitable period for vaccination of offspring appeared to be
      around 50 days of age. The bivalent vaccine against pasteurellosis and RHDV
      combined speed and longevity of the immune response. Immune protection against
      pasteurellosis and RHDV can thus be achieved with only one manipulation.

PMID- 14582743
TI  - Demonstration of alternative and classical complement pathway activity in
      colostrum from buffalo (Bubalus bubalis).
AB  - Buffalo colostrum caused lysis of unsensitized red blood cells (RBC) from sheep,
      goats, rabbits and chickens. RBC from cattle and buffalo were resistant to lysis.
      That lysis was due to the presence of natural antibodies to these RBC was ruled
      out since there was no reduction in haemolytic titres even after adsorption with
      the respective RBC. The addition of EGTA to the diluent had no effect on the
      haemolytic activity. These findings indicate the presence of alternative
      complement pathway (ACP) activity in buffalo colostrum. The haemolytic activity
      of buffalo complement for unsensitized rabbit RBC was reduced to very low levels
      by heating at 50 degrees C for 45 min. Treatment with zymosan also inhibited the
      haemolytic activity, while inulin had no effect. The maximum activity of ACP
      occurred in the presence of 4 mmol/L Mg(2+) in the diluent. The range of ACP
      activities in colostrum from buffaloes varied from 4.06 to 8.48 CH50 units/ml.
      Using a standard system for titrating the classical complement pathway and rabbit
      red blood cells sensitized with goat haemolysin, the range of complement activity
      in buffalo colostrum was 4.81-6.77 CH50/ml.

PMID- 14582744
TI  - A low-molecular-weight fraction of bovine colostrum and milk enhances the
      oxidative burst activity of polymorphonuclear leukocytes.
AB  - Bovine colostrum and milk contain many immunomodulatory components. The low
      molecular-weight fraction (< 10 kDa) was separated from colostrum and milk by gel
      filtration chromatography, and its effect on the oxidative burst of bovine
      polymorphonuclear leukocytes (PMNL) was investigated in vitro. The oxidative
      burst activity induced by Staphylococcus aureus was considerably enhanced when
      PMNLs were incubated with this low-molecular-weight fraction. However, phorbol 12
      myristate 13-acetate did not trigger a burst after priming with this fraction.
      The oxidative burst activity enhanced by this fraction was reduced after heating.
      These results confirmed that a low-molecular-weight substance(s) of less than 10
      kDa, present in bovine milk and colostrum, enhances the oxidative burst activity
      of PMNL.

PMID- 14582745
TI  - Comparative pharmacokinetics of diphenhydramine in camels and horses after
      intravenous administration.
AB  - The pharmacokinetics of diphenhydramine (DPHM) was compared in camels (n = 8) and
      horses (n = 6) following intravenous (i.v.) administration of a dose of 0.625
      mg/kg body weight. In addition, the metabolism and urinary detection time of DPHM
      was evaluated in camels. The data obtained (median and range in brackets) in
      camels and horses, respectively, were as follows. The terminal elimination half
      lives (h) were 1.58 (1.13-2.58) and 6.11 (4.80-14.1), and the total body
      clearances (L/h per kg) were 1.42 (1.13-1.74) and 0.79 (0.66-0.90). The volumes
      of distribution at steady state (L/kg) were 2.38 (1.58-4.43) and 5.98 (4.60-8.31)
      and the volumes of the central compartment of the two compartment pharmacokinetic
      model were 1.58 (0.80-2.54) and 2.48 (1.79-3.17). All the pharmacokinetic
      parameters in camels were significantly different from those of horses. Five
      metabolites of DPHM were tentatively identified in the camel's urine. Two
      metabolites, diphenylmethoxyacetic acid and 1-(4-hydroxyphenyl)
      phenylmethoxyacetic acid, were present in the acid fraction. Two metabolites,
      desamino-DPHM and diphenylmethanol, were identified in the basic fraction, in
      addition to DPHM itself, which was present mainly as a conjugate. Even after
      enzymatic hydrolysis, DPHM could be detected for up to 24 h in camels after an
      i.v. dose of 0.625 mg/kg body weight.

PMID- 14582746
TI  - Comparative plasma pharmacokinetics and tolerance of florfenicol following
      intramuscular and intravenous administration to camels, sheep and goats.
AB  - Florfenicol, a monofluorinated analogue of thiamphenicol, has a broad
      antibacterial spectrum. The pharmacokinetics of florfenicol was studied following
      a single intravenous (i.v.) or intramuscular (i.m.) injection at a dose of 20
      mg/kg body weight in healthy male camels, sheep and goats. The concentration of
      florfenicol in plasma was determined using a microbiological assay.
      Pharmacokinetic analysis was performed using a two-compartment open model.
      Following i.m. administration, the maximum plasma concentration of florfenicol
      (Cmax) reached in camels, sheep and goats was 0.84 +/- 0.08, 1.04 +/- 0.10 and
      1.21 +/- 0.10 microg/ml, respectively, the the time required to reach Cmax
      (t(max)) in the same three respective species was 1.51 +/- 0.14, 1.44 +/- 0.10
      and 1.21 +/- 0.10 h. The terminal half-life (t(1/2)beta) and the fraction of the
      drug absorbed (F%) in camels, sheep and goats were 151.3 +/- 16.33, 137.0 +/-
      12.16 and 127.4 +/- 11.0 min, and 69.20% +/- 7.8% , 65.82% +/- 6.7% and 60.88% +/
      5.9%, respectively. The MRT in the same three respective species was 4.01 +/-
      0.45, 3.42 +/- 0.39 and 2.98 +/- 0.32 h. Following i.v. administration, the
      terminal half-life (t(1/2)beta) and total body clearance (Clbeta) in camels,
      sheep and goats were 89.5 +/- 9.2, 78.8 +/- 8.3 and 71.1 +/- 8.9 min and 0.33 +/-
      0.04, 0.30 +/- 0.03 and 0.27 +/- 0.03 L/h per kg, respectively. The area under
      the curve (AUC(0-infinity)) and the mean residence time (MRT) in the same three
      respective species were 60.61 +/- 6.98, 62.45 +/- 6.56 and 74.07 +/- 7.85
      microg/ml per h, and 2.71 +/- 0.31, 2.34 +/- 0.25 and 2.11 +/- 0.23 h. These data
      suggest that sheep and goats absorb and clear florfenicol to a broadly similar
      extent, but the rate and extent of absorption of the drug tends to be higher in
      camels. Drug treatment caused no clinically overt adverse effects. Plasma enzyme
      activities and metabolites indicative of hepatic and renal functions measured 1,
      2, 4 and 7 days following the drug treatment were within the normal range,
      indicating that the drug is safe at the dose used.

PMID- 14582747
TI  - Genetic heterogeneity of bovine viral diarrhoea virus in Italy.
AB  - The genetic characteristics, of 38 field isolates of bovine viral diarrhoea virus
      (BVDV) collected in 1999 from sick or healthy and persistently infected cattle of
      dairy farms situated in northern Italy, were investigated. A partial 5'
      untranslated region (5'-UTR) sequence of each isolate was determined and a
      phylogenetic analysis was performed. All the isolates were classified as
      belonging to the BVDV-1 genotype and could be assigned to different BVDV-1
      groups, namely BVDV-1b (n = 20), BVDV-1d (n = 6) and BVDV-1e (n = 10). Two
      remaining isolates could be classified as BVDV-1f and BVDV-1h, respectively.
      These results provided evidence for genetic heterogeneity of BVDV in Italy, and
      contribute to a better knowledge of the circulation of BVDV strains, and to their
      classification.

PMID- 14582748
TI  - Bovine herpesvirus 5 (BoHV-5) in bull semen: amplification and sequence analysis
      of the US4 gene.
AB  - Bovine herpesvirus type 5 (BoHV-5), which is potentially neuropathogenic, was
      detected in clinical samples of bovine semen, both directly and after isolation
      in cell culture, using a nested PCR system for amplifying the US4 gene.
      Nucleotide sequences generated from the amplicons were analysed and deposited at
      GenBank (NCBI, Bethesda, MD, USA) under the accession numbers AF298174 and
      AF330157. Alignment of these sequences and previously deposited sequences of BoHV
      1 and BoHV-5 showed 82% and 98% similarity, respectively. The bulls, which were
      maintained at an artificial insemination centre, had presented no clinical signs,
      indicating that bovine semen should be screened for BoHV-5 to prevent
      transmission of the virus.

PMID- 14582749
TI  - An outbreak of diarrhoea in one-week-old piglets caused by group A rotavirus
      genotypes P[7],G3 and P[7],G5.
AB  - Thirty-two group A isolates of rotavirus detected in faecal samples from
      diarrhoeic piglets, were selected for P and G genotyping using a Multiplex RT
      PCR. Ten isolates, from animals less than 8 days old, characterized an outbreak
      of diarrhoea caused by group A rotavirus in animals. P[7],G3 (CRW8-like) and
      P[7],G5 (OSU-like) genotypes were detected in 5 animals each. Isolates of a group
      A rotavirus of genotypes compatible with the OSU prototype were those most
      frequently identified in single infections in older animals (20/32 strains). In
      addition to these, 20 isolates from piglets with diarrhoea caused by group A
      rotavirus, collected between May 1998 and June 1999, but not from the outbreak
      month, were analysed. These isolates were used to compare the types observed on
      the farm outside the outbreak in May 1999 and the CRW8-like genotype was found in
      none of these faecal samples. P[7],G5 was the most frequent genotype (10/20
      strains). No outbreak of diarrhoea caused by rotavirus in 1-week-old piglets was
      found in any other period during the 13 months of this study.

PMID- 14582750
TI  - A comparison of peripheral nerve regeneration in acellular muscle and nerve
      autografts.
AB  - Regeneration of the rat sciatic nerve through acellular muscle and nerve
      autografts was evaluated 6-28 days postoperatively by the sensory pinch test,
      immunocytochemical staining for neurofilaments, and light and electron
      microscopy. Data points generated by the pinch test were plotted against
      postoperative time periods and by the use of regression analysis the initial
      delay period for muscle grafts was determined to 10.3 days. This value was
      similar to that previously published for acellular nerve grafts (9.5 days), but
      significantly longer than that for fresh nerve grafts (3.6 days). The calculated
      regeneration rate (slope of the regression line) for muscle grafts (1.8 mm/day)
      did not differ significantly (p > 0.05) from that calculated for acellular nerve
      grafts (2.1 mm/day) or for fresh nerve grafts (1.5 mm/day). The front of
      regenerating axons shown by axonal neurofilament staining confirmed the pinch
      test results. Both types of acellular grafts were repopulated with host non
      neuronal cells and the muscle graft contained occasional ectopic muscle fibres.
      Remnants of graft basal laminae were evident at the ultrastructural level. These
      results indicate the suitability of either acellular muscle or nerve grafts for
      nerve repair despite their prolonged initial delay periods compared with
      conventional fresh nerve grafts.

PMID- 14582751
TI  - Comparative study of topical use of vasodilating solutions.
AB  - Vasodilating effects of topically applied lignocaine, papaverine, and
      chlorpromazine were compared in rats, using a PO2 tissue perfusion monitor and
      histological analysis. The period of vasospasm was significantly shorter with the
      use of either 10% lignocaine, 2% papaverine, or 0.25% chlorpromazine than with
      the use of 2% lignocaine. Although our study found that no particular
      vasodilating agent was more effective than the others, we did find that although
      lignocaine 2% and 5% might not be able to fully relieve vasospasm, 10%
      lignocaine, 2% papaverine, or 0.25% chlorpromazine are recommended to relieve
      vasospasm clinically as they do not injure the arterial wall.

PMID- 14582752
TI  - Spring-mediated cranioplasty compared with the modified pi-plasty for sagittal
      synostosis.
AB  - The aim of this study was to compare the safety, morphological outcome, and
      degree of parental satisfaction of the new spring-mediated cranioplasty with
      those of the modified pi-plasty in the management of sagittal synostosis. Ten
      patients with non-syndromic sagittal synostosis treated with the spring-mediated
      cranioplasty were followed prospectively. A control group of 10 sex-matched
      patients operated on with the modified pi-plasty procedure was chosen.
      Cephalometric radiographs were obtained preoperatively and postoperatively at 1
      year of age. Cephalic index, axial width ratio, length ratio, width ratio and
      height ratio were used as objective measures of outcome. Parents were sent a
      questionnaire to obtain a subjective aesthetic assessment of outcome.
      Significantly less blood replacement was required (p = 0.003), and shorter
      duration of postoperative anaesthesia (p = 0.030) and postoperative hospital stay
      (p = 0.013) were found in the spring-mediated cranioplasty group. There were no
      complications or deaths in either group. Also significant was the inter-group
      difference in the postoperative change in the height ratio (p = 0.030), the most
      change being seen in the spring group. The change in the subjective parental
      aesthetic evaluation of skull shape was significant in both groups. In
      conclusion, the spring-mediated procedure was morphologically more effective than
      the modified pi-plasty procedure in the management of sagittal synostosis with
      the additional benefits of less blood transfusion needed and shorter duration of
      hospital stay.

PMID- 14582753
TI  - Secondary correction of the wide nasal root in bilateral nasal deformity
      associated with cleft lip in five Oriental patients.
AB  - Secondary correction of bilateral nasal deformity associated with a cleft lip is
      common. However, few reports have referred to the correction of the wide nasal
      root. In this study we describe a technique other than osteotomy for the
      correction of the wide nasal root used in five Oriental patients with bilateral
      nasal deformity associated with cleft lip. Satisfactory results were obtained,
      and two representative cases are described.

PMID- 14582755
TI  - Non-operative treatment of displaced avulsion fractures of the ulnar base of the
      proximal phalanx of the thumb.
AB  - Treatment of displaced or rotated avulsion fractures of the ulnar base of the
      proximal phalanx of the thumb remains controversial. There is limited information
      on the outcome of management of these injuries by non-surgical means. We
      undertook a retrospective follow-up study of the non-operative treatment of these
      fractures. The study included 28 thumbs that were stable to lateral stress
      testing at the time of initial investigation. The patients were treated by
      immobilisation of the thumb in a spica cast. The mean follow-up interval was 2.5
      years (range 1-4). None of the patients changed their permanent employment or was
      unable to participate in their usual sporting activities. Twenty-six patients
      (93%) reported no pain on movement of the thumb. At follow-up, grip and pinch
      strengths did not differ significantly on the injured and non-injured sides. No
      thumbs showed instability on stress testing. The fractures had a 40% rate of bony
      union and 60% rate of fibrous non-union. All the patients were satisfied with
      their outcome. None of the patients was operated on after treatment. Non
      operative treatment is recommended in cases of displaced or rotated avulsion
      fractures provided that there is no lateral instability of the
      metacarpophalangeal joint. Patients with unstable thumbs should always be treated
      surgically.

PMID- 14582754
TI  - Pedicled myocutaneous and muscle flaps in the management of complicated
      cardiothoracic problems.
AB  - The purpose of this study was to review our experience with the management of
      patients with complicated cardiothoracic problems by the use of pedicled
      myocutaneous or muscle flaps, and discuss the various methods of reconstruction.
      Over the last 11 years, we have treated 54 patients with complicated
      cardiothoracic problems by reconstruction with pedicled myocutaneous or muscle
      flaps. The underlying causes were chest wall tumours (n = 13), radionecrosis of
      the chest wall (n = 12), deep or chronic sternal infections (n = 25), and
      bronchopleural fistulas (n = 4). The most commonly used muscles for
      reconstruction were pectoralis major and the rectus abdominis. Our results
      compare favourably with those reported elsewhere. We conclude that although the
      use of pedicled myocutaneous or muscle flaps is not free of complications, it is
      an effective and reliable method for the management of patients with complicated
      cardiothoracic problems.

PMID- 14582756
TI  - Arthrodesis of the distal interphalangeal joint using a bioabsorbable rod as an
      intramedullary nail.
AB  - There are several fixation techniques for arthrodesis of the distal
      interphalangeal joint. Since February 1999 we have used a bioabsorbable (poly-L
      lactide, PLLA) rod as an intramedullary nail for arthrodesis of 15 distal
      interphalangeal joints and one interphalangeal joint of the thumb. The advantages
      include the absence of protruding hardware that would require removal, and
      technical simplicity. Preoperative diagnoses included degenerative arthritis in
      five patients, post-traumatic arthritis in 10 patients, and non-union after
      arthrodesis with crossed Kirschner wires in one patient. All patients were
      observed until there was clinical and radiographic evidence of fusion with the
      mean interval to fusion of 8 weeks (range 6-12). There were two cases of minor
      intermittent local swelling, which resolved. Fixation with a PLLA rod for
      arthrodesis of the distal interphalangeal joint is a simple and effective
      technique.

PMID- 14582757
TI  - Reconstruction of microform cleft lip.
AB  - Partial cleft of the orbicularis oris muscle without skin and mucosa can also be
      called "discontinuity of the orbicularis oris muscle" or "subepithelial cleft".
      Microform cleft lip or mini-cleft lip are better definitions. We present two
      women aged 25 and 29 years old who complained of vermilion notching, vertical
      depression on the upper lip, and asymmetry of lower lateral cartilage of the
      nose. The "discontinuity of the muscle" was found at operation in both cases and
      reconstructed successfully.

PMID- 14582758
TI  - Suturing of a textured breast implant filled with cohesive silicone gel to
      prevent dislocation.
AB  - We present a case of unilateral anchoring of a style 410 breast implant filled
      with cohesive silicone gel (McGhan) with four 3/0 braided polyester (Mersilene)
      sutures. Reoperation after one week and magnetic resonance scanning after six
      months showed no leakage or bleeding of the prosthesis. Fixation is possible
      because of the development of cohesive silicone gel in breast implants. Follow up
      of this patient is necessary for evaluation of long term results.

PMID- 14582760
TI  - Neuropathy related to Crohn's disease treated by peripheral nerve decompression.
AB  - Neurological complications of Crohn's ileitis have been reported, and the
      aetiology ascribed to vitamin deficiencies and iatrogenic treatment. In this
      report we describe a patient who developed multiple areas of nerve compression in
      lower and upper extremities. After failure of conservative treatment, she was
      successfully treated surgically. As far as we know this has not been reported
      before.

PMID- 14582759
TI  - Necrotising fasciitis and myositis that originated from gastrointestinal
      bacterial infection: two fatal cases.
AB  - We present two cases of aggressive myofasciitis after gastrointestinal
      infections. The first patient developed necrosis of the legs over 5 days and he
      died on the 20th day. Vibrio vulnificus was cultured. The second patient
      developed bullae on his thigh and he died the next day. Streptococcus pyogenes
      was cultured.

PMID- 14582761
TI  - Lyophilised polyurethane membrane dressing for surgically-separated
      pseudosyndactyly in epidermolysis bullosa.
AB  - The results of paraffin gauze dressing and lyophilised polyurethane membrane
      dressing were studied in a patient with surgically-separated pseudosyndactyly of
      dystrophic epidermolysis bullosa. Polyurethane membrane dressing decreased the
      time to epithelialisation and the need for anaesthesia.

PMID- 14582762
TI  - Deviation of a finger at the proximal interphalangeal joint caused by juxta
      articular exostosis.
AB  - An exostosis around the interphalangeal joint can cause deformity of a finger. We
      present two children with deviated fingers as a result of exostoses that
      developed near the proximal interphalangeal joints and were successfully treated
      by resection and closed wedge osteotomy.

PMID- 14582763
TI  - Dislocation of the pisiform bone after severe crush injury to the hand.
AB  - The pisiform bone dislocated in a 56-year-old worker who had a crush injury of
      his wrist. Open reduction and reconstruction of the ligaments resulted in
      proximal subluxation of the pisiform bone and post-traumatic arthritic changes.
      Other authors recommend that excision of the pisiform is considered to be a more
      appropriate method of treatment.

PMID- 14582764
TI  - Statins in multiple sclerosis: a new therapeutic option?

PMID- 14582765
TI  - Diagnosis of MS: a comparison of three different clinical settings.
AB  - In order to compare a newly established diagnostic clinic with two existing
      clinical settings in the management of the diagnostic phase of multiple sclerosis
      (MS), a retrospective audit was performed over a 12-month period comparing the
      length of time, adherence to recently published standards and price charged in
      diagnosing MS in three different clinical diagnostic settings operating within
      the same hospital: a specifically designed demyelinating disease diagnostic
      clinic (DDC), a general neurology clinic (GNC) and an inpatient investigation
      unit (IIU). An audit tool was created to measure the standards advocated by the
      UK MS Society on management of the diagnostic phase of MS. The costing tool was
      the price charged to health authorities. A randomized retrospective case note and
      referral letter review method was used. The entry criterion was a confirmed
      diagnosis of MS documented in the medical notes following investigation during
      the period April 1999-April 2001. The time between referral and first appointment
      favoured the DDC with a mean time of 5.9 weeks, compared to 7.7 weeks for the GNC
      and 10.0 weeks for the IIU. The mean times between the first appointment and
      receipt of results were 4.7 weeks (DDC), 18.8 weeks (GNC) and 21.2 weeks (IIU).
      Prices ranged from pounds sterling 395-pounds sterling 790 (DDC), pounds sterling
      95-pounds sterling 380 (GNC) and pounds sterling 1940-pounds sterling 2700 (IIU).
      This study suggests that the UK MS Society standards are achievable in most areas
      without excessive additional costs and provides evidence that the DDC offers a
      better service than other existing models.

PMID- 14582766
TI  - Elispot assay detection of cytokine secretion in multiple sclerosis patients
      treated with interferon-beta1a or glatiramer acetate compared with untreated
      patients.
AB  - The mechanisms behind the beneficial effects of interferon-beta1a (IFN-beta1a)
      and glatiramer acetate (GA) in the treatment of multiple sclerosis (MS) are still
      uncertain. Altered cytokine patterns have been suggested including inhibition of
      proinflammatory cytokines like interferon-gamma (IFN-gamma) and enhancement of
      anti-inflammatory cytokines such as interleukin-4 (IL-4). Twenty-nine patients
      with MS (10 untreated, nine treated with IFN-beta1a and 10 with GA) were
      investigated with elispot of peripheral blood mononuclear cells. Spontaneous and
      myelin induced (myelin basic protein (MBP), myelin oligodendrocyte glycoprotein
      (MOG)-14-39 and MOG 63-87) IFN-gamma, IL-4, IL-5 and IL-10 secretion was studied.
      We found a significant reduction of spontaneous IFN-gamma, IL-4 and IL-5, but no
      difference in IL-10 secreting cells in both groups of treated patients compared
      with the untreated patients. Myelin-specific responses showed a significant
      decrease of IFN-gamma and an increase of IL-5, but no change in IL-4 and IL-10
      secreting cells in treated compared with untreated patients. Both treatment
      groups revealed similar cytokine secretion patterns except for a more pronounced
      decrease of both spontaneous and MOG 14-39 induced IL-4 secretion in the IFN
      beta1a treated group. Thus, immunological effects of IFN-beta1a and GA were
      similar showing that disease promoting Th1 (IFN-gamma) cells were reduced while
      the potentially beneficial Th2 response (IL-4) was maintained.

PMID- 14582767
TI  - Safety and tolerability of cyclophosphamide 'pulses' in multiple sclerosis: a
      prospective study in a clinical cohort.
AB  - To assess the safety and tolerability of cyclophosphamide (CTX) 'pulse' therapy
      in progressive or very active multiple sclerosis (MS), we reviewed our experience
      in a cohort of MS patients who have been treated and prospectively followed-up in
      our Department since 1997. One hundred and twelve patients received intravenous
      CTX in monthly 'pulses' for 12 months at the dosage of 700 mg/m2 of body surface,
      then bimonthly for another 12 months. We evaluated the frequency and the severity
      of side-effects, as well as overall tolerability by the patient perspective using
      a visual analogue scale (VAS). Side-effects resulted in the discontinuation of
      therapy in 20 (18%) cases. Serious side-effects were observed in 24 patients
      (21.4%), most commonly definitive amenorrhea (33.3% of fertile women),
      hypogammaglobulinemia (5.4%), and hemorrhagic cystitis (4.5%). Malignancies were
      diagnosed in four (3.6%) subjects, three of whom were previously treated with
      azathioprine (AZA). Finally, 81.8% of the patients judged the treatment regimen
      as very or relatively acceptable and tolerable. Our data point to a reasonable
      safety and tolerability of CTX 'pulse' therapy. Further trials are needed to
      definitively assess the efficacy of CTX as an alternative therapeutic option for
      progressive or very active MS.

PMID- 14582768
TI  - Interferon beta in relapsing-remitting multiple sclerosis: an independent
      postmarketing study in southern Italy.
AB  - This independent, population-based surveillance study monitored the efficacy and
      safety of interferon beta (IFNbeta) products in 1033 patients with relapsing
      remitting multiple sclerosis (RRMS) from 15 centres in Italy. Relapses, Expanded
      Disability Status Scale (EDSS) scores, and adverse events were evaluated for up
      to 24 months. Data of patients with a baseline EDSS score < or = 3.5 are
      reported. The proportions of relapse-free patients were similar among the groups
      at 12 and 24 months (P = 0.10). IFNbeta products produced significant reductions
      from baseline in relapse rates at 12 and 24 months (P < 0.001), with no
      differences among treatments (P = 0.2). There were no significant differences in
      mean EDSS change among groups at 12 or 24 months. The IFNbeta-1b group showed a
      higher incidence of adverse events during the first year of treatment (P < 0.05)
      than IFNbeta-1a groups, and more withdrawals (10%) compared with Avonex (5%) at
      24 months. IFNbeta products are equally effective in low disability RRMS, but
      IFNbeta-1a may have a more favorable efficacy/tolerability ratio.

PMID- 14582770
TI  - Predictors of alternative medicine use by multiple sclerosis patients.
AB  - OBJECTIVE: To determine the frequency of alternative medicine use among multiple
      sclerosis (MS) patients, and the factors which predict such use. METHODS: We
      examined 20778 MS patients enrolled in the North American Research Consortium on
      Multiple Sclerosis (NARCOMS) Patient Registry, residing in the USA. We used
      demographic and clinical data to create multivariate logistic regression models
      for i) lifetime use of any alternative medicine, ii) lifetime use of any
      alternative provider (AP), and iii) lifetime use of each of the three most common
      AP. RESULTS: 20387 patients provided data regarding alternative medicine use.
      Lifetime use of any alternative medicine was 54% and current use was 30%.
      Chiropractors (51%), massage therapists (34%), and nutritionists (24%) were the
      most commonly used AP. In all five models, use of alternative medicine was most
      strongly predicted by use of a conventional provider, and more modestly by
      disease factors indicating more severe or prolonged disease. Predictive power of
      the models was poor (c-index = 0.62-0.68), despite good fits for the data.
      CONCLUSIONS: Demographic factors play only a minimal role in predicting the use
      of alternative medicine in this MS population while disease factors play a
      slightly stronger role. There must be other factors involved that may include
      accessibility, social acceptability and cultural factors. Given the frequency of
      alternative medicine use by this patient population, further characterization of
      these factors is important.

PMID- 14582769
TI  - Symptomatic medication use in multiple sclerosis.
AB  - Multiple sclerosis (MS) is one of the most studied neurological diseases,
      although scarce attention has been placed on symptomatic therapy. The aim of the
      study was to evaluate the frequency of medication prescription for the major
      symptoms related to MS in order to better understand the needs of patients. The
      study was conducted during an epidemiological survey in the province of Genoa,
      Italy. Out of 856 patients with MS in the study area, 665 agreed to participate
      in a structured interview. Two hundred and forty-nine (37%) subjects, with a mean
      age of 53 years and a mean Expanded Disability Status Scale (EDSS) score of 5.2,
      were taking at least one symptomatic medication. Four hundred and sixteen (63%)
      subjects, with a mean age of 49 years and a mean EDSS score of 4.5, were not
      using symptomatic therapy. The most commonly treated symptoms were pain (28%),
      spasticity (27%) and mood disorder (16%), while bladder dysfunction (8%) and
      fatigue (3%) were less frequently treated with medication. Seventy-seven patients
      (12%) were taking medications for reasons not directly related to MS. This cross
      sectional study underlines the frequency of medication prescription for symptoms
      such as spasticity and pain, while other common symptoms, such as bladder
      dysfunction and fatigue, may perhaps be undertreated. The present findings also
      underline the need for clinical trials on symptomatic therapies.

PMID- 14582771
TI  - An MRI study of Chlamydia pneumoniae infection in Italian multiple sclerosis
      patients.
AB  - We amplified sequences of the Chlamydia pneumoniae (CP) major-outer membrane
      protein in the cerebrospinal fluid (CSF) from 23 of 107 (21.5%) relapsing
      remitting or secondary progressive multiple sclerosis (MS) patients and two of 77
      (2.6%) patients with other neurological diseases (OND) (P = 0.00022). CP+
      patients showed magnetic resonance imaging (MRI) evidence of more active disease
      (P = 0.02) compared to CP- MS patients and tended to have an anticipation of age
      at disease onset (32.3 +/- 12 versus 28.5 +/- 10 years; P = ns) causing a longer
      disease duration (7.5 +/- 5 versus 4.4 +/- 4 years; P = 0.016) at the time of
      clinical evaluation. These findings, although indirectly, suggest that CP
      infection of the central nervous system (CNS) might affect disease course in a
      subgroup of MS patients.

PMID- 14582772
TI  - Improved resolution of human cerebrospinal fluid proteins on two-dimensional
      gels.
AB  - Proteomics combines two-dimensional gel electrophoresis and peptide mass
      fingerprinting and can potentially identify a protein(s) unique to disease. Such
      proteins can be used either for diagnosis or may be relevant to the pathogenesis
      of disease. Because patients with multiple sclerosis (MS) have increased amounts
      of immunoglobulin (Ig) G in their cerebrospinal fluid (CSF) that is directed
      against an as yet unidentified protein, we are applying proteomics to MS CSF,
      studies that require optimal separation of proteins in human CSF. We found that
      recovery of proteins from CSF of MS patients was improved using ultrafiltration,
      rather than dialysis, for desalting. Resolution of these proteins was enhanced by
      acetone precipitation of desalted CSF before electrophoresis and by fractionation
      of CSF using Cibacron Blue sepharose affinity chromatography. Improved protein
      recovery and resolution will facilitate excision from gels for analysis by
      peptide mass fingerprinting.

PMID- 14582773
TI  - Lack of apolipoprotein-E exacerbates experimental allergic encephalomyelitis.
AB  - Experimental autoimmune encephalomyelitis (EAE) was found to have a chronic and
      significantly worse course in apolipoprotein-E (apoE) deficient female mice when
      compared with matched controls. Disease measures compared included incidence of
      EAE (64% versus 31%, P < 0.05, chi2 test), maximal clinical score (average +/- SD
      2.81 +/- 2.5 versus 0.75 +/- 1.1, P < 0.01, Mann-Whitney test) and mortality
      (27.3% versus 0%, P = 0.02, Mann-Whitney test and chi2 test). ApoE deficient mice
      had significantly increased lymphocyte proliferation responses to both myelin
      antigens and mitogens and significantly more infiltrating lesions in the central
      nervous system (CNS) in histopathology. Defective neuronal repair mechanisms and
      enhanced immune reactivity in apoE deficient mice may explain our findings.
      Clinical implications for MS are discussed.

PMID- 14582774
TI  - Interobserver agreement on Poser's and the new McDonald's diagnostic criteria for
      multiple sclerosis.
AB  - We assessed the interobserver agreement on the diagnosis of multiple sclerosis
      (MS) in a study sample consisting of 41 MS (15 relapsing remitting, two secondary
      progressive, five primary progressive and 19 presenting their first clinical
      attack) and three non-MS cases. Clinical and paraclinical information was
      recorded in standardized forms. Four neurologists were asked to make a diagnosis
      using Poser's and McDonald's criteria and to assess MRI scans according to the
      McDonald's guidelines. In terms of the kappa statistic (kappa), we found a
      moderate agreement on the overall diagnosis using both Poser's and McDonald's
      criteria (kappa, respectively 0.57 and 0.52). As for distinct diagnostic
      categories, we observed a moderate to substantial agreement for the three
      McDonald categories (range of kappa values 0.49-0.64) and a fair to substantial
      agreement for the nine Poser categories (range of kappa values 0.37-0.67). Taking
      into account clinical information, the agreement on dissemination over time was
      substantially higher (kappa = 0.69) than that found on dissemination over space
      (kappa = 0.46). In contrast, for MRI assessment, the agreement for spatial
      dissemination was substantial (kappa = 0.74) compared with the fair agreement
      (kappa = 0.25) yielded by dissemination over time. The new McDonald's criteria
      yield a good overall diagnostic reliability, and compare favourably with Poser's
      classification in terms of agreement on distinct diagnostic categories.

PMID- 14582775
TI  - Longitudinal disability curves for predicting the course of relapsing-remitting
      multiple sclerosis.
AB  - BACKGROUND: Multiple sclerosis (MS) is a lifelong disease affecting young adults
      that ultimately can lead to significant neurological disability. Identifying the
      rate of progression of disability for an individual patient early in the disease
      process can influence treatment decisions as well as enable monitoring of the
      disease overtime. OBJECTIVE: The aims of the present study were to develop
      longitudinal disability curves to assess disease progression in patients with
      relapsing remitting MS. The construction of these disability curves was based on
      the mean yearly Expanded Disability Status Scale (EDSS) scores, represented as a
      major percentile group. To determine their predictive ability, validation of the
      percentile curves was performed. METHODS: Using the Multiple Sclerosis Center
      computerized database of 1540 patients' records, we identified 1317 subjects with
      a definite MS and a relapsing-remitting disease course. Longitudinal disability
      curves were constructed for a subgroup of relapsing-remitting patients (n = 1001)
      with consecutive (3-6 months) EDSS assessments for a period of up to 10 years
      since onset. The constructed disability curves were then validated in an
      additional subgroup of relapsing-remitting MS patients (n = 268) with continuous
      follow-up visits for a period of 10 years. RESULTS: Statistical procedures using
      parametric and nonparametric regression procedures were applied to the data in
      two stages. In the first stage, selected major percentiles were generated for up
      to 10 years from disease onset with a variety of parametric procedures including
      moving averages. In the second stage, the empirical percentiles were smoothed to
      obtain the final disability progression curves. The log-rank test for equality
      demonstrated a significant adjustment between the initial percentile assignment
      and disability progression (P < 0.001). Life table analysis demonstrated that the
      probability of deviating from the initially assigned percentile to a higher
      percentile over time, representing more severe disability than expected, is in
      the range of 6.5% for the 50th percentile to 10.4% for the 75th percentile.
      CONCLUSION: Longitudinal disability curves can be used in MS to assess individual
      patient disability, can contribute to the overall clinical impression of disease
      progression and can add to the evaluation of immunomodulating treatment effects
      overtime.

PMID- 14582776
TI  - Effect of visual information on step-tracking movements in patients with
      intention tremor due to multiple sclerosis.
AB  - The effect of visual information on step-tracking movements was studied in 18
      patients with intention tremor due to multiple sclerosis (MS) and 15 healthy
      controls. Parricipants performed a slow wrist step-tracking task with stationary
      targets under five visual feedback conditions. The display of the target and
      movement cues was selectively withdrawn to examine the effects of visual
      information on intention tremor and movement accuracy. Results showed that
      intention tremor was most pronounced when visual display of both target and
      movement cues was available. Withdrawing visual information of the limb movement
      reduced tremor more than withdrawing the visual display of the target cues. Both
      the patient and control group was less accurate when the display of limb movement
      was occluded. Patients, however, were more dependent on visual information of the
      limb movement for accurate motor performance than healthy controls. When the
      visual display of the limb movement was partially occluded between or near to the
      targets, tremor decreased without deterioration of movement accuracy.

PMID- 14582778
TI  - Fatigue and its association with sociodemographic variables among multiple
      sclerosis patients.
AB  - OBJECTIVE: To explore the relationship between fatigue, sociodemographic and
      clinical variables in a population of patients with multiple sclerosis (MS).
      RATIONALE: There is a need to identify empirical relationships with possible
      antecedents of fatigue among patients with MS. METHODS: A mailed questionnaire
      designed to survey sociodemographic variables and the Fatigue Severity Scale
      (FSS) was mailed to 502 individuals from the population of patients with definite
      MS in the city of Oslo. A total of 368 (73%) responded. Clinical data were
      collected from the Oslo City MS-Registry. RESULTS: The prevalence of fatigue in
      this population was 60.1%. The FSS score showed a negative correlation with
      education (r = -0.15, P < 0.01) and a positive correlation with age (r = 0.20, P
      < 0.001) and time since disease onset (r = 0.11, P < 0.05). When controlled for
      gender, level of education and time since disease onset, the data showed a
      positive relationship between fatigue and age (P < 0.001) among patients with
      primary progressive (PP) disease. This relationship between age and fatigue was
      not found among patients with relapsing-remitting/secondary progressive (RR/SP)
      disease. CONCLUSION: The negative relationship between level of formal education
      (FE) and fatigue among individuals with RR/SP disease suggests that behavioral
      factors may be among the antecedents of fatigue in this patient group. In
      contrast to normative data from the general population, our findings revealed no
      differences in fatigue related to gender Thus, this study supports the hypothesis
      that there are disease-specific antecedents of fatigue among patients with MS.

PMID- 14582777
TI  - Cognitive fatigue during a test requiring sustained attention: a pilot study.
AB  - BACKGROUND: Fatigue is common in multiple sclerosis (MS), but difficulty
      quantifying fatigue severity has impeded studies of its characteristics,
      mechanisms, and therapeutics. Motor fatigue can be objectively measured as the
      decline in strength occurring during sustained contractions. Analogous declines
      in cognitive performance occur during tasks requiring sustained attention.
      OBJECTIVE: To objectively measure cognitive fatigue as a decline in performance
      during tests requiring sustained attention. DESIGN/METHODS: Patients with
      clinically stable MS (n = 20) and healthy controls (n = 21) with comparable age,
      gender, and education completed the Paced Auditory Serial Addition Test (PASAT)
      and the Digit Ordering Test (DOT) at two identical test sessions separated by 4
      10 days, within a month after two practice sessions. Cognitive fatigue was
      quantified with two pre-specified methods for each test. The reliability of
      cognitive fatigue assessments was evaluated with intraclass correlation
      coefficients (ICCs) and construct validity was evaluated using correlations with
      measures of self-reported fatigue, cognition, and overall impairment/disability.
      RESULTS: MS patients had an average of 18.7 items correct on the first 20 items
      of the PASATand 17.8 correct on the last 20 items, quantified as 5.3-5.8%
      declines in performance using the different measurement methods (P = 0.01,
      rejecting the null hypothesis of zero mean decline). Although MS patients as a
      group demonstrated a similar decline at both sessions, ICCs were relatively low.
      Control patients did not demonstrate significant declines in performance during
      PASAT administration, but tests comparing declines in MS patients and controls
      did not demonstrate significant differences. Fatigue was not demonstrated using
      the DOT, and test-retest reliability was very poor. CONCLUSIONS: MS patients have
      objectively measurable cognitive fatigue during administration of the PASAT.

PMID- 14582779
TI  - Sick leave and professional assistance for multiple sclerosis individuals in
      Vasterbotten County, northern Sweden.
AB  - The aims of this study of a cross-sectional multiple sclerosis (MS) population in
      Vasterbotten County, northern Sweden, were to estimate the prevalence of sick
      leave, professional assistance and housing; to study risk factors for sick leave;
      and to estimate the odds for sick leave in comparison with the general population
      of the county. The consequences of MS-related incapacity on the socioeconomic
      factors studied were considerable. Almost half (45%) of prevalent MS cases aged
      18-64 years were fully sick listed and only one-third (35%) were not sick listed
      at all. Every fourth individual in the prevalence population received
      professional assistance, and 9% were living in care homes or special apartments
      for the disabled. Multiple logistic regression analysis identified the Expanded
      Disability Status Scale (EDSS) as the strongest predictor of sick leave. The time
      from symptom onset to full sick leave leading to temporary or permanent
      disability pension was significantly shorter for cases with progressive onset,
      higher age at onset and in males. The risk of full sick leave due to MS was six
      times higher than in the general population.

PMID- 14582780
TI  - Is Devic's neuromyelitis optica a separate disease? A comparative study with
      multiple sclerosis.
AB  - Devic's neuromyelitis optica (NMO) associates optic neuritis and myelopathy
      without other neurological signs. Many patients with NMO may be diagnosed as
      having multiple sclerosis (MS). However, there have been no previous studies
      comparing these two pathologies and it is still unclear if NMO is a separate
      entity or a subtype of MS. In the present study, we compared a series of NMO
      patients with a series of MS patients for whom optic neuritis or myelopathy was
      the presenting symptom, in order to determine the place of NMO in the spectrum of
      MS. We retrospectively studied 30 patients diagnosed with NMO and we compared
      these patients with 50 consecutive MS cases revealed by optic neuritis or acute
      myelopathy. MS patients were only included if a relapse occurred demonstrating
      time and space dissemination. We compared the two groups in terms of clinical
      presentation, laboratory findings (MRI and CSF) and clinical outcome. NMO
      patients were older and more frequently women than MS patients but the difference
      was not significant. CSF and MRI data were clearly different: oligoclonal bands
      (OCB) were found in 23% of NMO cases and 88% of MS (P < 0.001), abnormal brain
      MRI data were observed in 10% of NMO cases and 66% of MS (P < 0.001) and a large
      spinal cord lesion was observed in 67% of NMO cases and 7.4% of MS cases (P <
      0.001). Clinical outcome was evaluated as more severe in the NMO group (P <
      0.001). On the basis of clinical data, all NMO patients but three had
      dissemination in time and space. When we included MRI parameters, only two of the
      NMO patients met criteria for MS and one of the MS patients met criteria for NMO.
      Our study demonstrates that NMO and MS should be considered as two different
      entities. The respective criteria for NMO and MS were able to distinguish these
      two pathologies but only when MRI data were applied. This finding could have
      implications for future therapeutic trials.

PMID- 14582781
TI  - Neuromyelitis optica after a spinal anaesthesia with bupivacaine.
AB  - We report the case of a 53-year old woman who developed a neuromyelitis optica
      (NMO or Devic's syndrome) after a spinal anaesthesia with bupivacaine. To our
      knowledge, the use of bupivacaine in human has not been associated to
      neurological complications like myelitis or NMO. The pathogenesis of this
      complication will be discussed.

PMID- 14582782
TI  - Pattern reversal visual evoked potentials as a measure of visual pathway
      pathology in multiple sclerosis.
AB  - BACKGROUND: Pattern reversal visual evoked potentials (PRVEPs) have a well
      documented role in diagnosis of multiple sclerosis (MS), but their value as a
      visual function surrogate remains controversial. METHODS: We evaluated PRVEP in
      37 patients with MS who were participating in a long-term follow-up study
      following a phase III trial of interferon beta-1a (Avonex). Patients were
      examined to determine the Kurtzke Extended Disability Status Score (EDSS),
      multiple sclerosis functional composite (MSFC), contrast letter acuity (CLA), and
      had cranial MRI scans to determine whole brain atrophy (BPF). PRVEP was evaluated
      for P100 latency, amplitude, and waveform morphology. Two summary scores were
      created: for Score A, abnormal latencies, morphologies, and amplitudes of each
      individual eye were added; for Score B, abnormal latencies, morphologies, and
      amplitude ratio between eyes was determined. Sixteen patients in this group also
      had PRVEP at the time they enrolled in the clinical trial, eight years
      previously. RESULTS: At the follow-up exam, over 75% of patients had abnormal
      PVEP parameters while visual acuity (VA) was abnormal only in 59%. Increased
      PRVEP latency over the eight-year period correlated with deterioration assessed
      by EDSS (P = 0.006), BPF (P = 0.0001), and MSFC (P = 0.0041). Score A was
      significantly correlated with EDSS, BPF, CLA, cognitive function, and quality of
      life assessed with the Sickness Impact profile. No correlation was seen with the
      MSFC. CONCLUSIONS: The results indicate that PRVEP measures MS-related pathology,
      and can provide not only diagnostic but also prognostic information during
      evaluation of MS patients.

PMID- 14582783
TI  - Blastomycosis in nondomestic felids.
AB  - Blastomycosis was diagnosed in six nondomestic felids from eastern Tennessee,
      including two Asian lions (Panthera leo persicus), one African lion (Panthera
      leo), one Siberian tiger (Panthera tigris), one cheetah (Acinonyx jubatus), and
      one snow leopard (Panthera uncia). Clinical signs included lethargy, anorexia,
      weight loss, dyspnea, sneezing. ataxia, and paresis. Variable nonspecific changes
      included leukocytosis, monocytosis, moderate left shift of neutrophils, moderate
      hypercalcemia, hyperproteinemia, and hyperglobulinemia. Thoracic radiographs
      revealed interstitial and alveolar changes, consolidation or collapse of a lung
      lobe, bullae formation, and a pulmonary mass. Agar gel immunodiffusion (AGID)
      serology for Blastomyces dermatitidis was performed in five felids and was
      positive in three. The tiger had cerebral blastomycosis and was positive for AGID
      serologic tests of both cerebrospinal fluid and serum. One percutaneous lung
      aspirate in the snow leopard and one bronchial aspirate in an Asian lion
      demonstrated B. dermatitidis organisms. whereas tracheal wash samples and a nasal
      discharge were nondiagnostic in others. Treatment with itraconazole was attempted
      in four cats. The tiger improved before euthanasia, whereas the others did not
      survive beyond initial treatments. In four felids, B. dermatitidis was found in
      the lungs and tracheobronchial lymph nodes associated with a florid
      pyogranulomatous reaction; the tiger had a pyogranulomatous encephalomyelitis,
      and the cheetah had a single pulmonary granuloma. Thoracic radiography, cytologic
      examination of lung lesion aspirates, and B. dermatitidis AGID serology should be
      performed on clinically ill zoo felids in endemic areas to rule out
      blastomycosis.

PMID- 14582784
TI  - Immunodeficiency associated with multiple concurrent infections in captive
      Pallas' cats (Otocolobus manul).
AB  - Five neonatal Pallas' cats (Otocolobus manul) at the Oklahoma City Zoo died from
      toxoplasmosis with concurrent herpesvirus infection. These multiple infections
      suggested underlying immunodeficiency, perhaps caused by concurrent infection
      with feline immunodeficiency virus (FIV); so blood samples were collected for
      serology, serum protein electrophoresis, lymphocyte proliferation assays, and
      cytokine analysis by reverse transcriptase-quantitative competitive polymerase
      chain reaction (RT-qcPCR). Resulting data were compared with data from FIV
      infected and control domestic short-haired cats. In addition, peripheral blood
      mononuclear cell cultures were propagated to detect FIV virus by both RT-qcPCR
      and detection of reverse transcriptase activity. Serum protein electrophoresis
      showed that four of six Pallas' cats had increased alpha, globulins. At least two
      Pallas' cats had decreased lymphoproliferation responses to mitogen. and all
      three tested animals exhibited defective interleukin-12 gene expression. Although
      these clinical and laboratory findings suggested an immunodeficiency syndrome,
      FIV infection could not be confirmed. On the basis of repeated blood test
      results, it can be concluded that nutritional, metabolic, or other systemic
      problems probably did not contribute to the disease syndrome. Further
      investigation of other possible causes of immunodeficiency, including a possible
      genetic component, in this population is needed.

PMID- 14582785
TI  - Seroprevalence of Neospora caninum and Toxoplasma gondii in captive and free
      ranging nondomestic felids in the United States.
AB  - Seven serum samples of 101 samples from nondomestic, captive and free-ranging
      felids from the United States were indirect fluorescent antibody positive for
      antibodies to Neospora caninum, whereas 44 samples were positive for antibodies
      to T. gondii. Although none of the captive animals displayed clinical signs of
      disease, nondomestic felids in the United States have been exposed to, and are
      likely infected with, N. caninum and T. gondii. This may have serious
      implications for zoological gardens exhibiting susceptible animals, such as
      kangaroos, close to felids.

PMID- 14582786
TI  - Plasmodium Juxtanucleare associated with mortality in black-footed penguins
      (Spheniscus demersus) admitted to a rehabilitation center.
AB  - Five black-footed penguins (Spheniscus demersus) admitted to the Southern African
      Foundation for the Conservation of Coastal Birds, in Cape Town, South Africa,
      died from malaria infection. Evidence for malaria as the cause of death included
      antemortem clinical signs, parasitemia, splenomegaly, pulmonary edema, and the
      presence of histologically visible schizonts in the reticuloendothelial system. A
      portion of the malarial small subunit ribosomal ribonucleic acid gene was
      detected by polymerase chain reaction from postmortem blood samples from all the
      birds. A species-specific variable region of this gene was compared with the same
      region on genes from other known avian malarial organisms, establishing that
      Plasmodium juxtanucleare was involved.

PMID- 14582787
TI  - Evidence of Brucella sp. infection in marine mammals stranded along the coast of
      southern New England.
AB  - After recent isolations of Brucella sp. from pinnipeds and cetaceans, a survey
      was initiated to investigate the prevalence of Brucella sp. infections and
      serologic evidence of exposure in marine mammals stranded along the coasts of
      Connecticut and Rhode Island. One hundred and nineteen serum samples from four
      species of cetaceans and four species of pinnipeds were collected from 1985 to
      2000 and tested for antibodies to Brucella sp. using the brucellosis card test,
      buffered acidified plate antigen test, and rivanol test. In addition, 20 of these
      were necropsied between 1998 and 2000, with lymphoid and visceral tissues
      cultured for Brucella sp. Three of 21 (14%) harbor seals (Phoca vitulina) and
      four of 53 (8%) harp seals (Phoca groenlandica) were seropositive. Brucella sp.
      was isolated from two of four (50%) harbor seals and three of nine (33%) harp
      seals. Of the five animals with positive cultures, two were seropositive and
      three seronegative. Brucella sp. was most frequently cultured from the lung and
      axillary, inguinal, and prescapular lymph nodes. Tissues from which Brucella sp.
      was isolated showed no gross or histopathologic changes. These results indicate
      that marine mammals stranded along the coast of southern New England can be
      exposed to and infected with Brucella sp.

PMID- 14582788
TI  - Antibiotic sensitivity and biochemical characterization of Fusobacterium spp. and
      Arcanobacterium pyogenes isolated from farmed white-tailed deer (Odocoileus
      virginianus) with necrobacillosis.
AB  - Bacterial cultures from 32 living and dead farmed white-tailed deer (Odocoileus
      virginianus) with necrobacillosis yielded Fusobacterium necrophorum from nine
      individuals, F. varium from six individuals, and Arcanobacterium pyogenes from 16
      individuals. The isolates were characterized biochemically using automated
      identification systems. Gram-stained smears suggested the presence of
      Fusobacterium spp. in eight cases from which organisms were not cultured. Minimum
      inhibitory concentration determinations in 23 strains of gram-negative anaerobic
      bacteria detected resistance to enrofloxacin and clindamycin. Enrofloxacin
      resistance was detected in A. pyogenes isolates, and although biochemical
      profiling indicated that the deer strains of A. pyogenes could be grouped, it is
      uncertain whether these biochemical characteristics correlate with antigenic or
      virulence factors. Deer-specific or autogenous vaccines may provide a useful
      alternative to generic vaccines.

PMID- 14582789
TI  - Comparison of etorphine-detomidine and medetomidine-ketamine anesthesia in
      captive addax (Addax nasomaculatus).
AB  - Thirty-five anesthetic events involving 15 captive addax (Addax nasonzaculatus)
      were performed between August 1998 and February 2002 using a combination of
      etorphine (33.7 +/- 7.9 microg/kg) and detomidine (21.9 +/- 4.6 microg/ kg) or a
      combination of medetomidine (57.4 +/- 8.6 microg/kg) and ketamine (1.22 +/- 0.3
      microg/kg), with or without supplemental injectable or inhalant anesthetic
      agents. Etorphine-detomidine anesthesia was antagonized with diprenorphine (107.1
      +/- 16.4 microg/kg) and atipamezole (100.9 +/- 42.4 microg/kg). Medetomidine
      ketamine anesthesia was antagonized with atipamezole (245.3 +/- 63.4 microg/kg).
      Animals became recumbent within 5 min when the combination of etorphine and
      detomidine was used and within 11 min when the combination of medetomidine and
      ketamine was used. Both drug combinations were suitable for use as primary
      immobilizing agents producing short-duration restraint and analgesia. Bradycardia
      was noted with both combinations. Further investigation of the cardiopulmonary
      effects of both combinations is warranted.

PMID- 14582790
TI  - Parasitologic analyses of the sifaka (Propithecus verreauxi verreauxi) at Beza
      Mahafaly, Madagascar.
AB  - A cross-sectional parasitologic survey of a population of wild sifaka
      (Propithecus verreauxi verreauxi) was conducted at the Beza Mahafaly Special
      Reserve in southwest Madagascar. Ninety fecal samples were collected from thirty
      1- to 30-yr-old male and female sifakas, and the formalin-preserved and polyvinyl
      alcohol-preserved specimens were examined using the zinc sulfate flotation and
      formalin-ethyl acetate sedimentation techniques. No intestinal parasites were
      recovered, possibly because the sifakas are arboreal in a dry, riverine habitat
      and lack human contact. Low rates of parasitic infection may have contributed to
      the evolution of later age at first reproduction and longer reproductive
      lifespan, for body mass, in Propithecus compared with other placental mammals.

PMID- 14582791
TI  - Hematology, plasma chemistry, serology, and Chlamydophila status of the waved
      albatross (Phoebastria irrorata) on the Galapagos Islands.
AB  - Venipuncture was performed on 50 adult, free-ranging waved albatrosses
      (Phoebastria irrorata) on Espanola, Galapagos Islands, Ecuador, to establish
      hematologic and plasma biochemistry reference ranges and to determine the
      prevalence of exposure to important domestic avian pathogens. Weights and plasma
      creatine phosphokinase activities differed significantly between males and
      females. Serum was tested for evidence of exposure to avian influenza, avian
      paramyxoviruses 1, 2, and 3, avian cholera, adenovirus groups 1 and 2, avian
      encephalomyelitis, Marek's disease, infectious bursal disease, and infectious
      bronchitis virus (Connecticut and Massachusetts strains). Of 44 birds, 29 (66%)
      seroreacted to adenovirus group 1, and four seroreacted to avian
      encephalomyelitis. Cloacal swabs were negative for Chlamydophila psittaci DNA.

PMID- 14582792
TI  - Intracapsular lens removal in a Przewalski's wild horse (Equus caballus
      przewalskii).
AB  - A 11.5-yr-old female Przewalski's wild horse (Equus caballus przewalskii)
      presented for unilateral blepharitis and drainage from the left eye. The left
      cornea was not ulcerated, and intraocular evaluation was hampered by severe
      corneal edema. The left eye appeared to respond positively to treatment with anti
      inflammatories and a topical mydriatic agent. During the ensuing 2 yr, there were
      minor episodes of epiphora from the left eye. The discharge then increased, and a
      luxated lens was noted during an examination by a veterinary ophthalmologist as
      part of the preshipment examination. Initially, the lens was located in the
      anterior compartment but was in the vitreal compartment at the time of surgery,
      complicating the intracapsular extraction. After successful removal of the lens,
      the horse was transferred to a new institution without incident, where it appears
      to have adapted well to its probable loss of vision in the left eye. No further
      episodes of uveitis, corneal edema, or epiphora have been reported, and the horse
      has successfully foaled at the new institution.

PMID- 14582793
TI  - Adult-onset hypothyroidism in a lynx (Lynx canadensis).
AB  - A 19-yr-old female lynx (Lynx canadensis) presented for an acute onset of
      anorexia and reluctance to move. Physical examination, radiography, hematology,
      and serum biochemistry revealed evidence of renal failure, presumptive uremic
      gastritis, chronic intervertebral disk disease at T13-L1, and markedly low serum
      levels of total thyroxine (1.54 nmol/L) and total triixodothyronine (0.55
      nmol/L). Twenty-five hours after its original presentation, the lynx exhibited
      horizontal nystagmus, which has been suggested as a clinical sign associated with
      hypothyroidism in domestic dogs. The lynx was euthanatized because of poor
      prognosis, and medical management concerns related to its chronic renal failure.
      Necropsy examination substantiated that the lynx had true hypothyroidism with 60
      90% of the thyroid gland replaced with adipose tissue. Although feline adult
      onset hypothyroidism may have low incidence, it should still be considered as a
      cause of nonspecific signs of disease in cats, as well as signs suggestive of
      hypothyroidism. Routine monitoring of baseline exotic felid thyroid levels
      throughout life would help to identify normal values and diagnose a potential
      disease that has obscure clinical signs.

PMID- 14582794
TI  - Treatment of a sole abscess in an Asian elephant (Elephas maximus) using regional
      digital intravenous perfusion.
AB  - Regional digital i.v. perfusion was used to treat a severe sole abscess
      associated with a wire foreign body in a 19-yr-old female Asian elephant (Elephas
      maximus) housed at the Paris Zoo. The cow presented with acute right forelimb
      lameness and swelling that persisted despite 4 days of anti-inflammatory therapy.
      Under anesthesia, a 10- x 0.5- x 0.5-cm wire was extracted from the sole of the
      right foot. There was a 2-cm-deep, 7-cm-diameter abscess pocket that was
      subsequently debrided. Regional digital i.v. perfusion was performed and repeated
      15 days later, using cefoxitin and gentamicin on both occasions. Between
      treatments, the cow received trimethoprim-sulfamethoxazole and phenylbutazone
      orally. Within 2 days of administering anesthesia and the first perfusion
      treatment, the lameness improved dramatically. When phenylbutazone was
      discontinued 1 wk after the first treatment, the lameness had completely
      resolved. At the second treatment, there was no evidence of further soft tissue
      infection, and the abscess pocket had resolved.

PMID- 14582795
TI  - A third report of "golf ball disease" in an Amazon River dolphin (Inia
      geoffrensis) associated with Streptococcus iniae.
AB  - An Amazon River dolphin (Inia geoffrensis) developed a dermatologic syndrome
      characterized by the occurrence of slow-growing, nodular, s.c. abscesses. Initial
      biopsies, cultures, and cytologic analysis of needle aspirates from the abscesses
      indicated steatitis with probable secondary, gram-negative bacterial infection.
      Treatment with dietary vitamin E supplement and broad-spectrum antibiotics
      yielded minimal improvement. Subsequent cultures revealed Streptococcus iniae in
      addition to several gram-negative bacteria. Vigorous surgical management of the
      abscesses, including lancing, debridement, and irrigation, combined with
      antimicrobial therapy specific for Streptococcus and gram-negative organisms, and
      improvement of the animal's diet and environmental water quality led to gradual
      recovery. When the animal was ill, it demonstrated an inflammatory leukogram and
      transient uremia. Streptococcus iniae is a serious pathogen of aquacultured
      fishes and humans and should be included in the differential diagnosis of chronic
      dermatopathy in river dolphins. Specific antimicrobial therapy, excellent water
      quality, surgical management of abscesses, and adherence to sanitary protocols
      should be observed in cases of suspected S. iniae infection in dolphins.

PMID- 14582796
TI  - Gallbladder adenocarcinomas in two captive African lions (Panthera leo).
AB  - Gallbladder adenocarcinomas in two captive African lions (Panthera leo), an 18-yr
      old male and a 17-yr-old female, are described in this report. Grossly, both
      lions had hemoperitoneum with thickened and sclerotic gallbladder walls.
      Histopathologically, the male's tumor was well differentiated and the female's
      was poorly differentiated with multinucleate giant cells. Both tumors were highly
      invasive and involved the gallbladder serosa. The male also had a tumor in the
      liver, and the female's tumor had disseminated to the serosal surfaces of
      abdominal organs. In both cases, neoplastic cell cytoplasm stained diffusely for
      cytokeratin AE-1/AE-3 and cytokeratin 7 and granularly for lysozyme on
      immunohistochemical staining.

PMID- 14582797
TI  - Anesthetic induction of captive tigers (Panthera tigris) using a medetomidine
      ketamine combination.
AB  - Six adult female tigers (Panthera tigris) were anesthetized repeatedly for
      elective medical procedures using 3 mg medetomidine and 200 mg ketamine i.m.
      Inductions were rapid and smooth, although supplemental ketamine was needed for
      safe transport after induction in 6 of 17 procedures. Reversal of the
      medetomidine-induced sedation with 15 mg atipamezole i.m. 59-232 min after
      induction resulted in smooth, rapid recoveries.

PMID- 14582798
TI  - Gross and microscopic lesions of polioencephalomalacia in a llama (Lama glama).
AB  - A 14-wk-old female llama (Lama glama) developed progressive neurologic disease
      characterized by stiff gait, circling, decreased mentation, and seizures. At
      necropsy, lesions were limited to the brain and consisted of bilateral necrosis
      of the cortical gray matter of the occipital lobes of the cerebral cortex. The
      primary microscopic alteration was bilateral laminar cerebrocortical necrosis,
      affecting mainly the deep laminae. Clinical disease, and gross and microscopic
      lesions were consistent with those of polioencephalomalacia.

PMID- 14582799
TI  - Effective use of tea to limit dietary iron available to starlings (Sturnus
      vulgaris).
AB  - Wild-caught starlings (Sturnus vulgaris) were fed an iron-enriched diet, with or
      without supplemental black tea leaves, to determine whether tea-derived tannins
      would prevent intestinal iron absorption. Hepatic biopsies were obtained to
      determine hepatic iron concentrations by atomic absorption spectroscopy. Hepatic
      iron concentrations increased significantly (P = 0.04) in 21 birds that consumed
      only the iron-enriched diet for 6 mo but not in the 20 birds that consumed the
      iron-enriched diet with tea leaf supplementation for the same time period.

PMID- 14582800
TI  - The neurobiology of addiction.
AB  - Drug addiction includes complex neurobiological and behavioural processes. Acute
      reinforcing effects of drugs of abuse are responsible for the initiation of drug
      addiction, whereas the negative consequences of drug abstinence have a crucial
      motivational significance for relapse and maintenance of the addictive process.
      The mesocorticolimbic system represents a common neuronal substrate for the
      reinforcing properties of drugs of abuse. Both dopamine and opioid transmission
      play a crucial role in this reward pathway. Common neuronal changes have also
      been reported during the abstinence to different drugs of abuse that could
      underlie the negative motivational effects of withdrawal. These changes include
      decreased dopaminergic activity in the mesolimbic system and a recruitment of the
      brain stress pathways. All drugs of abuse interact with these brain circuits by
      acting on different molecular and neurochemical mechanisms. The existence of
      bidirectional interactions between different drugs of abuse, such as opioids and
      cannabinoids, provides further findings to support this common neurobiological
      substrate for drug addictive processes.

PMID- 14582801
TI  - Biological markers in alcoholism.
AB  - Alcohol biomarkers include tests indicative of acute or chronic alcohol
      consumption (state markers), and markers of a genetic predisposition to develop
      alcohol dependence after chronic exposure (trait markers). While a comprehensive
      trait marker for alcohol dependence has not been identified, a number of
      successful state markers for monitoring drinking status are used clinically.
      These tests provide direct or indirect ways to estimate the amounts of alcohol
      consumed and the duration of ingestion, and to detect any harmful effects on body
      functions resulting from long-term misuse. The most obvious method to prove
      recent drinking is by demonstrating the presence of ethanol in body fluids or
      breath, but, because ethanol is cleared fairly rapidly from the body, this method
      is limited to detect only very recent drinking. Measurement of urinary 5
      hydroxytryptophol or ethyl glucuronide provide more sensitive methods to disclose
      recent drinking, because their washout constants are much longer than for
      ethanol. The liver functions test (GGT, AST and ALT in serum) and the mean
      corpuscular volume of erythrocytes (MCV) are among the standard diagnostic tools
      used to identify chronic alcohol exposure. The main disadvantage with these
      measures is that they have low sensitivity for recent excessive intake, and that
      raised levels may result from several causes besides heavy drinking, implying a
      low specificity for alcohol. Carbohydrate-deficient transferrin (CDT), which
      refers to changes in the carbohydrate composition of serum transferrin, is a more
      specific marker for identifying excessive alcohol consumption and monitoring
      abstinence during outpatient treatment. The alcohol biomarkers improves knowledge
      of drinking patterns in both individuals and populations, and they are also
      valuable tools for the objective evaluation of treatment efforts. Alcohol markers
      have, for example, found uses in early identification of at-risk and harmful
      drinking, and they help to monitor abstinence and relapse in response to
      outpatient treatment.

PMID- 14582802
TI  - Substitution management in opioid dependence.
AB  - Substitution treatment (replacement therapy) is the most widespread and the most
      frequently researched therapeutic approach to heroin dependence. At present, the
      "gold standard" is methadone maintenance, but the use of other agonists and of
      combined compounds with antagonists are increasingly used, especially
      Buprenorphine. This paper reviews the main findings from research and their
      consequences for best practice rules. The evolution and organisation of
      substitution treatment in Europe is described, indicating a major discrepancy in
      administrative regulations. Emerging trends are also mentioned, as well as the
      merits and limitations that mark the place of substitution treatment in a
      comprehensive therapeutic network for opioid dependence.

PMID- 14582803
TI  - Designer drugs: how dangerous are they?
AB  - Of the designer drugs, the amphetamine analogues are the most popular and
      extensively studied, ecstasy (3,4-methylenedioxymethamphetamine; MDMA) in
      particular. They are used recreationally with increasing popularity despite
      animal studies showing neurotoxic effects to serotonin (5-HT) and/or dopamine
      (DA) neurones. However, few detailed assessments of risks of these drugs exist in
      humans. Previously, there were no methods available for directly evaluating the
      neurotoxic effects of amphetamine analogues in the living human brain. However,
      development of in vivo neuroimaging tools have begun to provide insights into the
      effects of MDMA in human brain. In this review, contributions of brain imaging
      studies on the potential 5-HT and/or DA neurotoxic effects of amphetamine
      analogues will be highlighted in order to delineate the risks these drugs
      engender in humans, focusing on MDMA. An overview will be given of PET, SPECT and
      MR Spectroscopy studies employed in human users of these drugs. Most of these
      studies provide suggestive evidence that MDMA is neurotoxic to 5-HT neurones, and
      (meth)amphetamine to DA neurones in humans. These effects seem to be dose
      related, leading to functional impairments such as memory loss, and are
      reversible in several brain regions. However most studies have had a
      retrospective design, in which evidence is indirect and differs in the degree to
      which any causative links can be implied between drug use and neurotoxicity.
      Therefore, at this moment, it cannot be ascertained that humans are susceptible
      to MDMA-induced 5-HT injury or (meth)amphetamine-induced DA injury. Finally,
      although little is known about other amphetamine analogues there are important
      questions as to the safety of these designer drugs as well, in view of the fact
      that they are chemically closely related to MDMA and some have been shown to be 5
      HT neurotoxins in animals.

PMID- 14582804
TI  - Early intervention strategies in substance abuse.
AB  - Since the mid-eighties many efforts have been made to develop spezialized
      intervention strategies and interview techniques aiming at harm reduction and
      motivational enhancement in patients with substance related disorders. Firstly,
      the "Transtheoretical Model of Change" by Prochaska and DiClemente, which defines
      motivation as a dynamic process with several stage dependent intervention
      possibilities. Secondly, the "Motivational Interviewing" technique by Miller and
      Rollnick, who strongly suggest an empathic communication style deriving from
      humanistic psychology. It has been shown that especially persons in early stages
      of substance related disorders profited very well from such early interventions.
      Psychiatric institutions not involved in specialized addiction treatment have to
      face frequent comorbid substance abuse among their patients. Findings of the
      efficacy of early interventions in general psychiatry are encouraging. Despite
      there is strong evidence of efficacy of early and motivational intervention
      strategies in several medical fields, their implementation tends to be very
      difficult.

PMID- 14582805
TI  - Homogenizing alcoholism treatment across Europe.
AB  - Alcohol treatment ideologies and goals vary in different countries of Europe and
      have been influenced by cultures and drinking patterns. From the traditional high
      consumption wine countries of Southern Europe to the spirit drinking North
      European countries. However, due to the natural course of alcoholism, long-term
      alcohol dependent patients share common features independent from initial
      drinking patterns and cultural influences. This makes populations'
      characteristics and the result of treatment comparable within Europe, even though
      treatment approaches and selection of patients vary in different countries.
      Clinical trials using common measures for outcome of intervention have been
      performed in the last ten years in several countries of Europe. Outcome has been
      measured not only with the traditional definition of abstinence (or other
      drinking end-points), but also in terms of the subjective impact of disease and
      treatments on patients' lives. The discovery that different types of supportive
      therapies (alone or in combination with medications) do have positive influences
      on the progress of the alcoholic disease, improving the patients' quality of life
      (QoL) in all countries of Europe, shed a light of optimism on what, until
      recently, was considered an untreatable disease. SUMMARY: From the age when
      alcohol treatment outcomes were incorrectly measured and barely comparable
      because of different populations (especially from the USA), scarce description of
      intervention and goals of treatment, a great progress has been reached, in recent
      years, with new methodologies applied in Europe in clinical trials dealing with
      populations of alcoholics. Therapies do work in improving their well-being status
      and life expectancy in all countries of Europe.

PMID- 14582806
TI  - White birch.

PMID- 14582807
TI  - Local anesthetic adverse reaction evaluations: the role of the allergist.

PMID- 14582808
TI  - Ambient particulate air pollution and childhood asthma exacerbations.

PMID- 14582809
TI  - Is 3-mm less drowsiness important?

PMID- 14582810
TI  - Pharmaceutical characteristics that influence the clinical efficacy of inhaled
      corticosteroids.
AB  - BACKGROUND: Inhaled corticosteroids (ICSs) are the most effective therapy for the
      management of persistent asthma. The aim of ICS therapy is to achieve a high anti
      inflammatory effect in the airways with a concomitant low risk of unwanted local
      and systemic effects. Direct estimates of clinical efficacy and potency based on
      studies in humans are difficult to interpret. OBJECTIVE: To examine the
      challenges of using alternative estimates of ICS efficacy and potency, including
      pharmaceutical characteristics. DATA SOURCES AND STUDY SELECTION: Articles
      published from 1990 to 2002 on the potency, efficacy, and tolerability of ICSs
      were identified using MEDLINE and in-house databases and were then reviewed.
      Search terms included inhaled corticosteroid, budesonide, fluticasone,
      beclomethasone, mometasone, and potency. RESULTS: Differences among ICSs can be
      readily shown using preclinical measures, such as glucocorticoid receptor binding
      or skin blanching tests. However, pharmaceutical (delivery and pharmacokinetic)
      differences of ICSs can have a greater impact on clinical efficacy than in vitro
      potency differences. For example, the unique esterification of budesonide in the
      airways prolongs its local activity and may contribute positively to its efficacy
      and therapeutic index. Although comparative clinical trials suggest 6-fold
      differences in potencies among ICSs, there is currently no evidence to support
      differences in efficacy when they are administered at equipotent dosages.
      CONCLUSIONS: Greater preclinical potency of an ICS does not imply greater
      clinical efficacy. Pharmacokinetic factors can have a significant impact on
      relative clinical efficacy.

PMID- 14582811
TI  - Levothyroxine anaphylaxis? Vocal cord dysfunction mimicking an anaphylactic drug
      reaction.

PMID- 14582812
TI  - Evaluation of adverse reactions to local anesthetics: experience with 236
      patients.
AB  - BACKGROUND: Adverse reactions to local anesthetics (LAs) are frequently reported.
      Although most of these reactions are not immune mediated, many patients are
      referred to allergy clinics and undergo extensive evaluation. OBJECTIVE: To
      determine the prevalence of true LA allergy among the patients referred for
      suspected hypersensitivity and to evaluate the usefulness of the currently used
      evaluation protocol. METHODS: A total of 236 patients referred to our allergy
      clinic for investigation of LA hypersensitivity were included in this study. The
      evaluation protocol was composed of skin prick and intradermal tests, followed by
      subcutaneous challenge with unrelated LA preparations that contained
      preservatives. RESULTS: Skin prick and intradermal test results were negative for
      all subjects. No objective adverse reactions were observed during the challenge
      in all but 1 patient, who developed local erythema at the site of injection and
      later underwent an uneventful challenge with a different LA. CONCLUSIONS:
      Allergic reactions were not reproduced during testing and challenge with LA
      preparations that contained preservatives or preservatives with adrenaline in our
      large group of patients with suspected LA allergy. Since both prick and
      intradermal skin test results were negative in all the patients and did not
      provide us with useful information, we propose to modify the standard protocol by
      omitting intradermal tests and shortening the challenge. We also suggest that the
      whole procedure be performed with LAs that contain preservatives, which are
      usually the preferred preparations widely used in daily practice.

PMID- 14582813
TI  - Effects of ambient air pollution on symptom severity and medication use in
      children with asthma.
AB  - BACKGROUND: Exposure to air pollutants has been investigated as a possible cause
      of asthma attacks in children. OBJECTIVE: To investigate the short-term effects
      of air pollutants on a panel of 133 children with asthma who enrolled in the
      Childhood Asthma Management Program. METHODS: During screening, the children
      completed daily diary cards for an average of 58 days to indicate their
      medication use and asthma severity. We used ordinal logistic regression to
      compare the odds of a more serious relative to a less serious asthma attack, and
      we used a Poisson model to analyze medication use. In both analyses we
      accommodate dependence in the data and different periods of observation for study
      subjects. RESULTS: Our results indicate that a 10-microg/m3 increase in
      particulate matter less than or equal to 2.5 microm (PM2.5) lagged 1 day was
      associated with a 1.20 times increased odds of having a more serious asthma
      attack [95% confidence interval (CI), 1.05 to 1.37] and a 1.08-fold increase in
      medication use (95% CI, 1.01 to 1.15). A 10-microg/m3 increase in particulate
      matter less than or equal to 10 microm (PM10) increased the odds of a more
      serious asthma attack (odds ratio = 1.12; 95% CI, 1.04 to 1.22) and also
      increased medication use (relative risk = 1.05; 95% CI, 1.00 to 1.09).
      CONCLUSIONS: Increases in PM2.5 and PM10 are significantly associated with an
      increased risk of more severe asthma attacks and medication use in Seattle area
      children with asthma. We also found associations with carbon monoxide, but we
      believe that carbon monoxide is a marker for exposure to combustion byproducts.

PMID- 14582814
TI  - Fexofenadine hydrochloride, 180 mg, exhibits equivalent efficacy to cetirizine,
      10 mg, with less drowsiness in patients with moderate-to-severe seasonal allergic
      rhinitis.
AB  - BACKGROUND: Previous studies have shown that fexofenadine and cetirizine
      effectively relieve symptoms of seasonal allergic rhinitis (SAR). OBJECTIVE: To
      compare the effects of fexofenadine hydrochloride, 180 mg, and cetirizine, 10 mg,
      on symptoms, drowsiness, and motivation in patients with moderate-to-severe SAR.
      METHODS: In this 2-week multicenter, double-blind, randomized study, 495 subjects
      with moderate-to-severe SAR received once-daily fexofenadine hydrochloride, 180
      mg, or cetirizine, 10 mg, without regard to food intake. Daily 12-hour reflective
      (AM, PM) and instantaneous (AM) individual symptoms and total symptom score (TSS)
      were evaluated. Drowsiness and motivation were recorded daily using visual analog
      scale at 7 AM, 10 AM, and 3 PM. RESULTS: Between-treatment differences in
      reduction from baseline in AM instantaneous and 24-hour reflective TSS were -0.18
      [95% confidence interval (CI), -0.55 to 0.20) and -0.22 (95% CI, -0.59 to 0.15),
      respectively. Since CIs for reduction in TSS between treatments fell within a 0.7
      margin (defined a priori), treatments were considered statistically equivalent.
      Patients receiving fexofenadine experienced significantly less overall drowsiness
      vs baseline than those receiving cetirizine [-2.33 (95% CI, -3.80 to 0.86) vs
      0.37 (95% CI, -1.10 to 1.84), P = .0110]. There was a trend toward greater
      improvements in overall motivation with fexofenadine compared with cetirizine [
      2.36 (95% CI, -3.83 to 0.90) vs -0.30 (95% CI, -1.76 to 1.17), P = .0504].
      CONCLUSIONS: Once-daily fexofenadine hydrochloride, 180 mg, given for 2 weeks
      caused statistically and clinically equivalent improvement in symptoms and
      significantly less drowsiness va baseline, compared with cetirizine, 10 mg, in
      patients with moderate-to-severe SAR.

PMID- 14582815
TI  - Cytokine levels during symptomatic viral upper respiratory tract infection.
AB  - BACKGROUND: Previous studies suggest a role for locally produced proinflammatory
      cytokines in the development and expression of illness during experimental
      infection with a variety of respiratory viruses. However, most of these studies
      fail to make comparisons between symptomatic and asymptomatic infected subjects.
      OBJECTIVE: To compare the pattern of nasal cytokine elaboration in asymptomatic
      and symptomatic subjects experimentally infected with rhinovirus-39 (RV-39).
      METHODS: Healthy adults underwent experimental intranasal inoculation with a
      safety-tested clinical isolate of RV-39. Nasal lavages were collected, nasal
      symptoms were recorded, and expelled nasal secretions were weighed before and
      then daily for 6 days after challenge. Nasal lavages were submitted for viral
      culture and assayed for cytokine protein levels by enzyme-linked immunosorbent
      assay. RESULTS: Twenty-nine subjects were enrolled in the study. All subjects
      were infected as evidenced by viral shedding and/or seroconversion. Sixteen
      subjects were symptomatic and 13 were asymptomatic as evaluated by subject self
      report. During infection, significant increases in mean levels of nasal
      interleukin 6 (IL-6) (P = .01) and IL-1 (P = .02) were observed in symptomatic
      but not asymptomatic subjects. In symptomatic subjects, these increases were
      temporally related to the development of nasal symptoms and production of
      secretions. Mean levels of IL-8, IL-10, and tumor necrosis factor a were not
      increased in either group during infection. CONCLUSIONS: The results of this
      study demonstrate elevations in certain locally produced cytokines during
      symptomatic but not asymptomatic respiratory infection with RV-39. Future studies
      using selected anticytokine therapies may help elucidate the precise role of
      cytokines in mediating disease expression.

PMID- 14582816
TI  - Effects of triamcinolone on quality of life in patients with persistent allergic
      rhinitis.
AB  - OBJECTIVE: To study the effects of triamcinolone acetonide on health-related
      quality of life (HRQL) in adult patients with allergic rhinitis. METHODS: This
      study was conducted in South Africa as a placebo-controlled, multicenter,
      randomized, double-blind study. Following a 7-day baseline run-in, patients were
      treated for 28 days with either triamcinolone or placebo. Interviewer-assisted
      quality-of-life assessments were conducted using the Juniper Rhinoconjunctivitis
      Quality of Life Questionnaire (RQLQ). Total symptom scores, including nasal
      congestion, were measured using daily diary cards. RESULTS: A total of 337
      patients were recruited and 253 patients completed the study per protocol, of
      which 55 had seasonal allergic rhinitis (SAR) and 198 had persistent allergic
      rhinitis (PAR). Improvements in the mean scores per area of the RQLQ were
      significantly better with triamcinolone compared with placebo for the entire
      study group for activities (P = .04 at visit 4) and sleep, nasal symptoms,
      emotional problems, and overall score (P = .002, P = .04, P = .03, and P = .04,
      respectively, at visit 3). When the patients with SAR were separated from the
      patients with PAR in the analysis, improvement with triamcinolone was better than
      placebo only in the PAR patients. The overall investigator and patient
      assessments of relief favored triamcinolone. CONCLUSIONS: Triamcinolone given for
      4 weeks improves symptom scores and HRQL in patients with allergic rhinitis. The
      ability of triamcinolone to relieve nasal congestion symptoms in PAR patients was
      correlated with improvements in HRQL.

PMID- 14582817
TI  - A comparison of the effect of diphenhydramine and desloratadine on vigilance and
      cognitive function during treatment of ragweed-induced allergic rhinitis.
AB  - BACKGROUND: Decrements in cognitive performance are associated with the use of
      sedating antihistamines. Most, but not all, second-generation antihistamines have
      been found to be nonsedating. OBJECTIVE: To examine the central nervous system
      (CNS) profile of a new second-generation antihistamine, desloratadine. METHODS:
      Subjects with ragweed-induced allergic rhinitis (aged 18-60 years) who
      demonstrated a predetermined severity of symptoms after priming with ragweed
      pollen in the Environmental Exposure Unit were randomized to receive a single
      dose of desloratadine, 5 mg; diphenhydramine, 50 mg; or placebo. A comprehensive
      battery of repeatable, automated neuropsychological tests was administered to
      subjects before treatment (symptomatic baseline) and 90 minutes after taking
      study medication. RESULTS: Both desloratadine (P = .04) and diphenhydramine (P <
      .01) alleviated the symptoms of allergic rhinitis compared with placebo, but
      treatment with diphenhydramine was associated with clinically meaningful
      decrements on all vigilance parameters (P < .05 for desloratadine-diphenhydramine
      contrasts). Also, subjects treated with diphenhydramine performed significantly
      worse than subjects given desloratadine or placebo across all cognitive domains
      evaluated. Most effect sizes for the mean desloratadine and diphenhydramine
      differences were between 0.4 and 0.8 (moderate to high). Stanford Sleepiness
      Scale scores also indicated significantly more somnolence with diphenhydramine vs
      desloratadine or placebo (P < .001). There were no significant differences on any
      of the cognitive parameters between subjects treated with desloratadine and those
      given placebo. CONCLUSIONS: Desloratadine improved ragweed-induced allergic
      rhinitis symptoms without adversely affecting performance. Diphenhydramine
      improved allergic rhinitis symptoms but caused significant decrements in
      vigilance and cognitive functioning. Thus, efficacy of antihistamine treatment
      must be balanced against the associated effects on CNS functioning.

PMID- 14582818
TI  - Inherited mannose-binding lectin deficiency as evidenced by genetic and
      immunologic analyses: association with severe recurrent infections.
AB  - BACKGROUND: Mannose-binding lectin (MBL), an acute-phase serum protein of hepatic
      origin, plays an essential protective role in host innate immunity in targeting
      microbial pathogens for destruction via opsonization, enhancement of phagocytosis
      and complement activation. MBL deficiency, characterized by low serum MBL, has
      been attributed to genetic mutations in both structural and promoter regions of
      the gene coding for the protein. Concomitant MBL deficiency in patients with
      chronic immunologic disease has been associated with increased susceptibility to
      complicating infections that may hasten disease progression. OBJECTIVE: Few cases
      of inherited MBL deficiency in adults and possible associations with recurrent
      infection have been reported. To address this issue, we investigated the MBL
      profile of four generations within a single adult family whose members have
      experienced a variety of persistent infections. METHODS: MBL serum levels and MBL
      genotypes of each participating family member were ascertained by enzyme-linked
      immunoadsorbent assay and reverse transcriptase-polymerase chain reaction,
      respectively. MBL complement activation, as measured by C4b deposition against
      mannan-coated wells, was assayed using an enzyme-linked immunoadsorbent assay.
      Routine immunologic and cellular tests were carried out to evaluate the
      immunologic status of each family member. RESULTS: Six of the 7 family members
      screened carried one or more of the variant MBL alleles in their genotype and had
      correspondingly low serum MBL and reduced ability to affect C4b opsonization.
      Medical histories of the participating family members revealed an array of mild
      to severe recurrent infections despite no apparent immunodeficiency. CONCLUSIONS:
      Our studies show that MBL deficiency is an inherited characteristic and may be a
      crucial factor in maintaining immunologic health.

PMID- 14582819
TI  - Occupational asthma due to exposure to iroko wood dust.
AB  - BACKGROUND: Occupational asthma (OA) from iroko wood has been reported primarily
      in case reports. OBJECTIVE: To improve understanding of the pathogenesis of OA
      induced by iroko wood dust. METHODS: Three groups of woodworkers were included in
      this study: 9 workers who had clinically proven OA from iroko; 10 asymptomatic
      woodworkers; and 10 woodworkers with asthma. All patients underwent the following
      tests: a skin test with an iroko aqueous extract, specific IgE determination, and
      an iroko bronchial provocation test (IBPT). An eosinophil count was determined
      before and after the IBPT, and a methacholine inhalation test was performed after
      avoidance of exposure to iroko. Patients were asked to monitor their peak
      expiratory flow rates during a week at work followed by a week's vacation.
      RESULTS: In all patients with a personal history predictive of OA from iroko, a
      reduction of the peak expiratory flow rate and positivity to the IBPT while
      working with iroko were present. The latter test result showed a dual response,
      with a decrease in forced expiratory volume in 1 second from 25% to 32% at 10
      minutes and a further decrease from 35% to 43% at 8 hours; at 24 hours, the
      eosinophil count was higher (P = .046). In 4 patients, the intradermal test
      results with iroko extract were positive, whereas the skin prick test result and
      the specific IgE determination were negative in all patients. The methacholine
      test result was also positive. In the control groups, all the test results with
      iroko extract were negative. CONCLUSIONS: Our data suggest that OA due to iroko
      wood may be induced by immunologic mechanisms other than IgE-mediated immediate
      hypersensitivity reactions.

PMID- 14582820
TI  - Relationship among pulmonary function, bronchial reactivity, and exhaled nitric
      oxide in a large group of asthmatic patients.
AB  - BACKGROUND: Bronchial reactivity and exhaled nitric oxide (eNO) are not often
      used to monitor control and severity of asthma in clinical practice. OBJECTIVE:
      To evaluate the relationship among different physiologic measures (pulmonary
      function, nonspecific bronchial reactivity, and eNO) in asthmatic patients.
      METHODS: Cross-sectional, hospital-based study conducted in patients with varied
      asthma severity. RESULTS: A total of 392 patients participated in the study.
      There was no difference in eNO levels between patients taking inhaled
      corticosteroids (ICS group) and patients not receiving inhaled corticosteroids
      (NICS group). However, the percentage of predicted forced expiratory volume in 1
      second (FEV1) and the provocative dose of methacholine causing a 20% decrease in
      FEV1 were significantly lower in the ICS group compared with the NICS group
      (mean, 83.2%; 95% confidence interval [CI], 80.4%-86.0%; vs mean, 94.1%; 95% CI,
      91.1%-97.1%; P = .001; and geometric mean, 0.32 mg; 95% CI, 0.23-0.45 mg; vs
      geometric mean, 0.58 mg; 95% CI, 0.42-0.81 mg; P = .01; respectively). Patients
      with more severe bronchial hyperresponsiveness had a lower percentage of
      predicted FEV1 values (P < .001) and levels of eNO were significantly increased
      with increasing bronchial hyperresponsiveness (P < .001). There was no
      relationship between the percentage of predicted FEV1 and eNO. Atopic patients
      had significantly higher eNO levels than nonatopic patients (geometric mean,
      11.21 ppb; 95% CI, 10.07-12.49 ppb; vs geometric mean, 7.76 ppb; 95% CI, 6.11
      9.85 ppb; P = .006; respectively). CONCLUSIONS: eNO values are not related to the
      degree of airway obstruction but are related to airway reactivity and atopic
      status independent of inhaled corticosteroid use. Higher values of eNO are seen
      with increased airway reactivity.

PMID- 14582821
TI  - Rush venom immunotherapy in patients experiencing recurrent systemic reactions to
      conventional venom immunotherapy.
AB  - BACKGROUND: An unknown number of venom-allergic patients fail to reach the
      maintenance dose (MD) during the build-up period of conventional venom
      immunotherapy (VIT) due to recurrent systemic reactions (SRs). OBJECTIVE: To
      establish an alternative VIT protocol that will enable these patients to reach a
      full protective MD. METHODS: Venom-allergic patients who had experienced
      recurrent SRs during the build-up period of conventional VIT underwent rush VIT.
      RESULTS: Of the 9 patients who participated in this study, the 6 who underwent 8
      treatment courses tolerated the rush VIT well and reached the MD within 3 days.
      In 3 of these patients, mild cutaneous SRs were overcome with loratadine. In 2
      patients who experienced recurrent and more severe SRs, the original 3-day rush
      VIT had to be modified and extended to 5 days until the MD was reached. In a
      single patient who experienced an anaphylactic reaction, VIT was discontinued.
      CONCLUSIONS: Rush VIT is an appropriate therapeutic alternative that enables most
      patients with recurrent SRs throughout the build-up period of conventional VIT to
      reach a full protective MD.

PMID- 14582822
TI  - Resolution of fish allergy: a case report.
AB  - BACKGROUND: Fish allergy is one of the most common food allergies, and it is
      believed to be lifelong. There are no published reports, to my knowledge, of
      resolution of fish allergy. OBJECTIVE: To report a case of resolution of IgE
      mediated fish allergy. METHODS: The patient was a 68-year-old man with a history
      of fish-induced anaphylaxis who had previously undergone prick-puncture skin
      testing to several fish species. Additional skin testing was performed in October
      2002. Subsequently, he underwent an open challenge with halibut. RESULTS: The
      patient's previous skin tests showed him to have strongly positive reactions to
      several fish species. However, testing performed in October 2002 produced
      negative results to a number of fish species. In addition, he tolerated an open
      challenge with halibut. In the ensuing 8 months, he has regularly ingested
      salmon, cod, and halibut without experiencing any allergic reactions.
      CONCLUSIONS: This case illustrates that fish allergy is not invariably lifelong.
      Hence, allergists should consider reevaluating the allergy status of adults with
      a history of fish hypersensitivity.

PMID- 14582823
TI  - Severe reactions from roe without concomitant fish allergy.
AB  - BACKGROUND: Although fish allergy is common, no studies have been published on
      allergy to fish roe. OBJECTIVE: To describe 2 cases of IgE-mediated allergy to 2
      roe species. METHODS: Two patients, one with local symptoms and the other with
      anaphylaxis following ingestion of roe, underwent skin prick testing (SPT) with 2
      roe species, whitefish roe (WFR) and rainbow trout roe (RTR). Serum samples were
      taken for IgE measurement and immunoblotting to identify roe allergens.
      Inhibition studies were performed to scrutinize the cross-reactivity between the
      roes and to fish. RESULTS: The results of the SPTs with the roes were clearly
      positive in both patients but negative in control persons. The results of SPTs to
      all other foods were negative. Roe-specific IgE levels were elevated in the serum
      samples of both patients. Immunoblotting revealed different IgE-binding patterns
      of the extracts and different inhibition profiles with the serum samples. In WFR
      blotting, both serum samples detected a heavy IgE-binding band at approximately
      20 kDa, which was not inhibited with fish. Cross-reactivity between the roes was
      demonstrated in the patient with local symptoms from RTR but not in the patient
      with anaphylaxis from WFR. The first serum sample also detected several IgE
      binding bands in the RTR blot, the most intensive at 21 to 23 kDa and 30 kDa,
      which were partially inhibited by WFR and more completely with fish. The
      anaphylaxis patient did not detect allergens in the RTR blot. After the
      investigation, the patients have remained symptom free and able to consume all
      kinds of fish without problems. CONCLUSIONS: IgE-mediated allergy to roe is
      possible without concomitant fish allergy. Roe allergy should be explored in
      patients who test negative to fish but are suspected of having seafood-related
      allergy.

PMID- 14582824
TI  - Role of leukotriene receptor antagonists (LTRAs) in seasonal allergic rhinitis.

PMID- 14582825
TI  - Fungal contamination and air sampling.

PMID- 14582826
TI  - International Study of Asthma and Allergies in Childhood (ISAAC), in conjunction
      with step testing is not adequate as a screening for asthma.

PMID- 14582827
TI  - Carboxymethylcellulose allergy as a cause of suspected corticosteroid
      anaphylaxis.

PMID- 14582828
TI  - Shared means and meanings in vocal expression of man and macaque.
AB  - Vocalisations of six Macaca arctoides that were categorised according to their
      social context and judgements of naive human listeners as expressions of
      plea/submission, anger, fear, dominance, contentment and emotional neutrality,
      were compared with vowel samples extracted from simulations of emotional
      motivational connotations by the Finnish name Saara and English name Sarah. The
      words were spoken by seven Finnish and 13 English women. Humans and monkeys
      resembled each other in the following respects. 'Neutral', 'pleading' and
      'commanding' had a similar F0 level. Loud vocalisations of intense 'anger' and
      'fear' had both high F0, and the highest values were encountered for 'fear'.
      Compared with 'neutral', the audiosignal waveform of 'plea/submission' was more
      sinusoidal, seen in the spectrum as an attenuation of formants and an emphasis of
      the fundamental, whereas the signal waveform of 'commanding' was more complex
      corresponding to an increase in noise and a wider distribution of spectral
      energy. 'Frightened' samples included rather harmonic segments with emphasis of
      the fundamental, and 'angry' samples included more noise at the low end of the
      spectrum and often segments with low-frequency ( < 100 Hz) edged modulation.
      Sounds resembling soft and noisy 'content' grunts of the monkey do not appear in
      Finnish or English speech but 'content' utterances were, however, associated with
      low speech pressure, attenuation of harmonics and increase in noise.

PMID- 14582829
TI  - Clinical applications of a cognitive phonology.
AB  - It is noted that much previous work in phonology has attempted to provide
      economical theories of sound systems without explicitly attempting to provide
      theories that have psycholinguistic validity. The work of Bybee on a cognitive
      approach to phonology is described, and its possible application to disordered
      speech is considered. It is discussed that cognitive phonology, coupled with
      gestural phonology, provides descriptive as well as explanatory accounts of
      disordered speech, and has specific implications for approaches to therapy. The
      article concludes with a case study of child with severely unintelligible speech,
      where it seems that the insights of cognitive phonology provide both an
      explanation for and a description of her speech behaviors.

PMID- 14582830
TI  - The self-to-other ratio applied as a phonation detector for voice accumulation.
AB  - A new method for phonation detection is presented. The method utilises two
      microphones attached near the subject's ears. Simplified, phonation is assumed to
      occur when the signals appear mainly in-phase and at equal amplitude. Several
      signal processing steps are added in order to improve the phonation detection,
      and finally the original signal is sorted in separate channels corresponding to
      the phonated and non-phonated instances. The method is tested in a laboratory
      setting to demonstrate the need for some of the stages of the signal processing
      and to examine the processing speed. The resulting sound file allows for
      measurement of phonation time, speaking time and fundamental frequency of the
      subject and sound pressure level of the subject's voice and the environmental
      sounds separately. The present implementation gives great freedom for adjustment
      of analysis parameters, since the microphone signals are recorded on DAT tape and
      the processing is performed off-line on a PC. In future versions, a voice
      accumulator based on this principle could be designed in order to shorten
      analysis time and thus make the method more appropriate for clinical use.

PMID- 14582831
TI  - Speech recognition and dysarthria: a single subject study of two individuals with
      profound impairment of speech and motor control.
AB  - This study investigated the use of the speech recognition system Dragon Dictate
      as an augmentative method of computer access for two individuals with cerebral
      palsy, including severe motor dysfunction and dysarthria. Single subject design
      was used and measures of computer access system effectiveness and speech
      production were used before, during and after intervention. The users' original
      switch access system was compared to a combination of their switch access system
      and speech recognition, by counting the number of correct entries. Adding speech
      recognition increased the number of correct entries by 40% for one of the
      participants. The other participant did not complete the intervention protocol.
      An independent judge rated speech production. No changes in speech were observed.
      Dragon Dictate is time-consuming to learn and demands a high level of motivation,
      but can be beneficial to a person who has profound dysarthria and great
      difficulties in accessing the computer.

PMID- 14582832
TI  - Importance of treatment efficacy research in the area of stuttering.

PMID- 14582833
TI  - Mental pain: a multidimensional operationalization and definition.
AB  - An operationalization of mental pain is presented in three studies. The first
      study describes the operationalization of mental pain and the factor structure of
      the items produced by a content analysis of self-reports yielding a scale with
      nine factors: the experience of irreversibility, loss of control, narcissistic
      wounds, emotional flooding, freezing, estrangement, confusion, social distancing,
      and emptiness. Study 2 tested the relationship between mental pain and depression
      and anxiety in a normal population. Study 3 focused on the relationship between
      mental pain and coping. Mental pain is conceptualized as a perception of negative
      changes in the self and its functions that are accompanied by negative feelings.
      It is suggested that it can be meaningfully applied to the study of different
      mental states, life conditions, and transitions in life.

PMID- 14582834
TI  - Mental pain and its relationship to suicidality and life meaning.
AB  - Shneidman (1996) proposed that intense mental pain is related to suicide.
      Relatedly, Frankl (1963) argued that the loss of life's meaning is related to
      intense mental pain. The first goal of this research was to test Shneidman's
      proposition by comparing the mental pain of suicidal and nonsuicidal individuals.
      Meaning in life and optimism are the polar opposites of suicidality and
      hopelessness, and the examination of these variables in relation to mental pain
      was undertaken to provide a test of Frankl's proposition. In two studies, a
      relationship between a newly developed measure of mental pain--the Orbach &
      Mikulincer Mental Pain Scale, 2002 (OMMP; see also Orbach, Mikulincer, Sirota &
      Gilboa-Schechtman, 2002)--and suicidal behavior and life meaning were examined.
      Results confirmed both propositions. Implications for the study of mental pain
      and suicide are discussed.

PMID- 14582836
TI  - The Life Attitudes Schedule-Short Form: psychometric properties and correlates of
      adolescent suicide proneness.
AB  - The goals of the present study were to describe the psychometric properties of
      the Life Attitudes Schedule-Short Form (LAS-SF) in adolescents and provide
      criterion and construct validity data, including bivariate and multivariate
      associations with related risk behaviors. Anonymous questionnaires containing the
      LAS-SF and related measures were administered to 1,742 high school students in
      three states. Psychometric properties for LAS-SF items and total score were very
      good, and the LAS-SF was correlated with almost all of the examined risk
      behaviors, illustrating the broad range of problems measured by the instrument.
      LAS-SF total scores were associated with past suicide attempt, even after
      controlling for the impact of current depression. Clinical and research uses for
      the LAS-SF are discussed.

PMID- 14582837
TI  - The LSARS-II: Lethality of Suicide Attempt Rating Scale-Updated.
AB  - The concept of lethality is essential to the assessment of suicide risk; yet
      operational definitions of lethality for purposes of its measurement have been
      loose and varied. A number of scaling measures have been published in the
      literature, with no relative consensus on the best of these. In addition, only a
      few of these scales have published data on their psychometric properties. Of
      these, we argue that the best is the Lethality of Suicide Attempt Rating Scale
      (LSARS; Smith, Conroy, & Ehler, 1984). Presented here is a significantly revised
      and redesigned listing of drugs and chemicals and lethal ranges of ingestion (in
      caps, tabs, or ounces) by body weight to update that scale.

PMID- 14582835
TI  - Psychache and suicidality in adult mood disordered outpatients in Brazil.
AB  - Shneidman (e.g., 1998) has theorized that psychache--general psychological and
      emotional pain that reaches intolerable intensity--is an important suicide
      related variable, and indeed, represents a source of suicidal behavior. This
      conceptualization, while prominent and clinically and intuitively appealing, has
      received relatively little empirical scrutiny. In this study, we determined
      whether an index closely related to psychache, psychological quality of life,
      would display a special and resilient association to suicidality among 60 adult
      psychiatric outpatients in Brazil. All patients underwent structured clinical
      interviews and completed various clinical and quality-of-life measures. We found
      that the association between psychological quality of life and suicidality
      remained, even when depression, hopelessness, and other domains of quality of
      life were controlled. Psychache appears to deserve its place among key suicide
      related variables, and deserves the attention of clinicians working with suicidal
      people.

PMID- 14582838
TI  - Two models of adolescent self-mutilation.
AB  - Currently little research exists examining the theoretical underpinnings of self
      mutilation (SM) in community samples of adolescents. Two models, the hostility
      and anxiety reduction models, were simultaneously tested in order to determine
      whether SM in adolescence was characterized by greater feelings of anxiety and
      hostility. Four hundred and forty students were screened for the presence of SM.
      Sixty-one students who indicated that they hurt themselves as well as a
      comparison group of non-SM students completed the Hostility and Direction of
      Hostility Questionnaire (HDHQ), the Beck Anxiety Inventory (BAI), and an
      interview. Results indicate support for the hostility model of SM. Students who
      SM reported significantly more anxiety and more intropunitive and extrapunitive
      hostility. In addition, prior to self-mutilating feelings of both hostility and
      anxiety were described. Results are discussed with reference to both theoretical
      models.

PMID- 14582839
TI  - Coping responses of adolescent suicide attempters and their relation to suicidal
      ideation across a 2-year follow-up: a preliminary study.
AB  - The coping responses of 23 hospitalized adolescent suicide attempters were
      compared to those of 19 hospitalized non-attempters matched on diagnosis and
      demographics. Relative to the comparison group, suicide attempters made fewer
      effortful-approach and more automatic-approach coping responses, and were judged
      by trained raters to have coped less effectively. Coders' ratings of greater
      coping effectiveness among suicide attempters were associated with a greater
      decline in suicidal symptoms assessed at 6-month follow-up intervals across a 2
      year period. The findings are discussed in light of a model of coping that
      incorporates both individual differences and situational characteristics.

PMID- 14582840
TI  - Suicidal ideation and attempts in Norwegian police.
AB  - Studies on suicide among police show inconsistent results, thereby contributing
      to considerable speculation regarding why police officers commit suicide. The
      present paper is the first nationwide study on suicidal ideation and attempts
      among police. 3,272 Norwegian police completed Paykel's Suicidal Feelings in the
      General Population questionnaire. Lifetime prevalence of specific questionnaire
      items ranged from 24% for the feeling that life was not worth living, 6.4% for
      having seriously considered suicide, and 0.7% for attempted suicide. Independent
      predictors of serious suicidal ideation were marital status, subjective health
      complaints, reality weakness, anxiety, and depression. Serious suicidal ideation
      was mainly attributed to personal and family problems.

PMID- 14582841
TI  - A meta-analysis of police suicide rates: findings and issues.
AB  - Meta-analyses of police suicide rates and ratios to the comparison population
      were conducted using 101 samples from the literature. The large effect sizes (ES
      = .74) showed that suicide rates based on short time frames were significantly
      higher than for long time frames. There were regional differences such that rates
      in the Americas and Europe were higher than in the Caribbean and Asian regions.
      There were differences in rates between federal, regional, and municipal police
      forces. Issues researchers need to address include the use of long time frames;
      the reporting of more complete suicide statistics, including breakdowns by year,
      sex, and ethnic groups; and the rates for population comparison groups.

PMID- 14582842
TI  - A semistructured interview for psychologycal autopsy: an inter-rater reliability
      study.
AB  - This study developed and evaluated the inter-rater reliability of a
      semistructured interview for psychological autopsy (SIPA). The SIPA is composed
      of 69 items that are distributed into four modules (precipitators and stressors,
      motivation, lethality, intentionality). The interviews of 42 subjects, related to
      21 cases of suicide, were audiotaped and then transcribed and evaluated by the
      interviewer, and also evaluated by a research assistant and two referees who all
      acted independently. The SIPA was able to provide information that demonstrated a
      high degree of concordance (kappa) among the raters. The results of this study
      demonstrate that the SIPA is a very reliable instrument for psychological autopsy
      in cases of suicide.

PMID- 14582843
TI  - Scott Ames: a man giving up on himself.

PMID- 14582844
TI  - Serum cholesterol levels and suicide: a further comment.

PMID- 14582845
TI  - Mechanistic effect of NMSO3 on replication of human immunodeficiency virus.
AB  - NMSO3, a sulphated sialyl lipid, was evaluated for its efficacy against human
      immunodeficiency virus type 1 (HIV-1). The compound exhibited concentration
      dependent inhibition of HIV-1 replication in primary infection cell culture
      systems. Substantial inhibition was observed at concentrations of NMSO3 that
      showed little cytotoxicity. NMSO3 also exhibited anti HIV-1 activity in
      chronically HIV-1 infected cultures. The production of progeny viruses was
      completely abolished without cytotoxicity by continuous addition of NMSO3 to
      chronically infected U937 cells. Furthermore, in attempting to define the
      inhibitory mechanism of NMSO3, we investigated its effect on several steps of the
      HIV-1 replication cycle. NMSO3 competes with gp120 for binding to CD4 receptors
      on cells and inhibits the entry of HIV-1. By epitope analysis of the human CD4
      molecule, NMSO3 inhibits the binding of antibodies, which recognize the D1 domain
      of CD4. Moreover, semi-quantitative reverse transcribed polymerase chain reaction
      (RT-PCR) showed that the integrated provirus is transcriptionally inactive in
      NMSO3-treated cells, supporting the lack of progeny in the culture supernatant of
      chronically HIV-1-infected cells treated with NMSO3. These findings indicate that
      NMSO3 has a unique mechanism of action against HIV-1 in both primary and chronic
      infection, and may be a valuable compound for the treatment of HIV-1 infection.

PMID- 14582846
TI  - Synthesis and antiviral activities of 3-aralkylthiomethylimidazo[1,2-b]pyridazine
      derivatives.
AB  - The synthesis of novel substituted 3-aralkylthiomethylimidazo[1,2-b]pyridazines
      is reported. All of the synthesized compounds are devoid of antiviral activity
      against the replication of human immunodeficiency virus. However, compounds 6
      chloro-8-methyl-3-phenethylthioimidazo[1,2-b]pyridazine and 6-chloro-2-methyl-3
      phenethylthioimidazo[1,2-b]pyridazine are potent inhibitors of the replication of
      human cytomegalovirus in vitro, while compounds 6-chloro-2-methyl-3
      benzylthiomethylimidazo[1,2-b]pyridazine and 6-chloro-2-methyl-3-phenethyl
      thioimidazo[1,2-b]pyridazineare inhibitors of the replication of varicella-zoster
      virus. The results presented here suggest that compound 10 should be considered
      as a new lead in the development of antiviral agents.

PMID- 14582847
TI  - Design and synthesis of phosphonoacetic acid (PPA) ester and amide bioisosters of
      ribofuranosylnucleoside diphosphates as potential ribonucleotide reductase
      inhibitors and evaluation of their enzyme inhibitory, cytostatic and antiviral
      activity.
AB  - Continuing our investigations on inhibitors of ribonucleotide reductase (RNR),
      the crucial enzyme that catalyses the reduction of ribonucleotides to
      deoxyribonucleotides, we have now prepared and evaluated 5'-phosphonoacetic acid,
      amide and ester analogues of adenosine, uridine and cytidine with the aim to
      verify both substrate specificity and contribution to biological activity of
      diphosphate mimic moieties. A molecular modelling study has been conducted on the
      RNR R1 subunit, in order to verify the possible interaction of the proposed
      bioisosteric moieties. The study compounds were finally tested on the recombinant
      murine RNR showing a degree of inhibition that ranged from 350 microM for the UDP
      analogue 5'-deoxy-5'-N-(phosphon-acetyl)uridine sodium salt (amide) to 600 microM
      for the CDP analogue 5'-O-[(diethyl-phosphon)acetyl]cytidine (ester). None of the
      tested compounds displayed noteworthy cytostatic activity at 100-500 microM
      concentrations, whereas ADP analogue 5'-N-[(diethyl-phosphon) acetyl]adenosine
      (amide) and 5'-deoxy-5'-N-(phosphon-acetyl)adenosine sodium salt (amide) showed a
      moderate inhibitory activity (EC50: 48 microM) against HSV-2 and a modest
      inhibitory activity (EC50: 110 microM) against HIV-1, respectively.

PMID- 14582848
TI  - Synthesis and evaluation of antirhinovirus activity of 3-hydroxy and 3-methoxy 2
      styrylchromones.
AB  - Recently, we identified 2-styrylchromones as a new class of antirhinovirus
      flavonoids with moderate activity against both rhinovirus groups A and B. In
      order to improve the antiviral effect of the first series of tested 2
      styrylchromones, a hydroxy or methoxy group was introduced in position 3 of the
      chromone ring. Cytotoxicity and antiviral activity of the new synthesized
      compounds were evaluated in HeLa cell cultures infected with rhinoviruses 1B and
      14, selected as representative serotypes for viral groups B and A of human
      rhinoviruses (HRVs), respectively. These antiviral results compared to those
      obtained for 3-unsubstituted 2-styrylchromones indicate the greater potency of 3
      hydroxy and 3-methoxy derivatives against both serotypes.

PMID- 14582849
TI  - ME-609: a treatment for recurrent herpes simplex virus infections.
AB  - Studies in conventional murine models of HSV infection use immunologically naive
      animals. These models thus mimic primary infections rather than recurrent
      infections in humans. We have, therefore, used a newly developed mouse model that
      more closely mimics recurrent HSV infection in humans. In this model, the mice
      are infected, and zosteriform HSV-1 infection develops in the presence of a
      primed immune response using adoptive transfer of immunity (ATI) as we have
      described previously. Using the ATI mouse model, it has been shown that a more
      beneficial therapy for recurrent mucocutaneous HSV infection could be achieved by
      controlling both the viral replication and the inflammatory response to the
      virus. Topical treatment was initiated in this model at the time of first
      occurrence of symptoms and was given three times daily for 4 days. Topical
      treatment with ME-609 (which contains 5% acyclovir and 1% hydrocortisone) in the
      ATI mouse model was substantially more efficacious than 5% Zovirax cream, 1%
      hydrocortisone or no treatment, respectively. The beneficial properties of ME-609
      were also found to be superior to those of Zovirax cream when tested in the
      standard guinea pig model, representing a primary HSV infection. ME-609
      represents a novel treatment principle of recurrent HSV infections and the
      present paper summarizes the preclinical and early clinical experience of ME-609.

PMID- 14582851
TI  - Is it in, or is it out?

PMID- 14582850
TI  - Antiviral activity of CTC-8 against herpes simplex virus (HSV-1) in cell culture:
      evidence for a selective antiviral effect via a cellular mechanism.
AB  - A synthetic programme produced a series of compounds related to natural
      prostaglandins, which are known to affect the growth of a number of viruses.
      Several of the compounds showed potent biological activity including antiviral
      effects. The compound CTC-8 [(S)-4-tert-butyldimethylsilyloxy-2-cyclopenten-1
      one] contains the cyclopentenone ring of prostaglandin A1, but the extended side
      chains common to the prostaglandin family are truncated. The present study
      demonstrates that CTC-8 inhibits HSV-1 replication in cell culture at sub-toxic
      concentrations. The antiviral effect was evidenced by reduction in infectious
      virus yield, although the compound was not effective in the standard plaque
      reduction assay. Time-of-addition studies and other experiments provide a
      possible explanation for these results by suggesting that the antiviral activity
      is confined to a single cycle. Under the standard conditions of high-multiplicity
      infection in BHK cells it was notable that CTC-8 is most effective when added for
      a short period 6-8 h post-infection. Furthermore, multiple passage of HSV-1 in
      the presence of CTC-8 did not result in the selection of resistant mutants. The
      results of these and other experiments are consistent with the hypothesis that
      the mechanism by which CTC-8 inhibits virus replication involves a cellular
      target. These results encourage further research into the therapeutic potential
      of this series of compounds.

PMID- 14582852
TI  - Mammalian diurnality: some facts and gaps.
AB  - A major factor contributing to the evolution of mammals was their ability to be
      active during the night, a niche previously underused by terrestrial vertebrates.
      Diurnality subsequently reemerged multiple times in a variety of independent
      lineages. This paper reviews some recent data on circadian mechanisms in diurnal
      mammals and considers general themes that appear to be emerging from this work.
      Careful examination of behavioral studies suggests that although subtle
      differences may exist, the fundamental functions of the circadian system are the
      same, as seems to be the case with respect to the molecular mechanisms of the
      clock. This suggests that responses to signals originating in the clock must be
      different, either within the SCN or at its targets or downstream from them. Some
      features of the SCN vary from species to species, but none of these has been
      clearly associated with diurnality. The region immediately dorsal to the SCN,
      which receives substantial input from it, exhibits dramatically different rhythms
      in nocturnal lab rats and diurnal grass rats. This raises the possibility that it
      functions as a relay that transforms the signal emitted by the SCN and transmits
      different patterns to downstream targets in nocturnal and diurnal animals. Other
      direct targets of the SCN include neurons containing orexin and those containing
      gonadotropin-releasing hormone, and both of these populations of cells exhibit
      patterns of rhythmicity that are inverted in at least one diurnal compared to one
      nocturnal species. The patterns that emerge from the data on diurnality are
      discussed in terms of the implications they have for the evolution and neural
      substrates of a day-active way of life.

PMID- 14582853
TI  - A type-1 phosphoprotein phosphatase from a dinoflagellate as a possible component
      of the circadian mechanism.
AB  - Indicative of the importance of protein phosphorylation in the core circadian
      clock mechanism, chronically applied inhibitors of both protein kinases and
      phosphoprotein phosphatases have significant effects on the period, phase, and
      light-dependent regulation of circadian rhythms in the dinoflagellate
      Lingulodinium polyedrum. This study was aimed at identifying the presence of the
      affected phosphatase(s). Dephosphorylation of a PP1/PP2A-specific substrate by L.
      polyedrum extracts was inhibited by okadaic acid only at concentrations greater
      than 100 nM, as in vivo, by mammalian inhibitor-2 (I-2), and by an endogenous
      inhibitor with properties similar to I-2, indicating that a type-1 protein
      phosphatase (PP1) was predominant. A cDNA encoding a highly conserved PP1 was
      isolated, the 1st such signaling molecule identified in dinoflagellates. Antisera
      specific for this type of phosphatase recognized a 34 kDa protein in L. polyedrum
      extract, this being the same size as the PP1 encoded by the isolated cDNA. These
      findings are consistent with the suggestion that the L. polyedrum PP1 may be a
      part of the clock mechanism in this species.

PMID- 14582854
TI  - Cryptochrome, compound eyes, Hofbauer-Buchner eyelets, and ocelli play different
      roles in the entrainment and masking pathway of the locomotor activity rhythm in
      the fruit fly Drosophila melanogaster.
AB  - The fly Drosophila melanogaster possesses five photoreceptors and/or
      photopigments that appear to be involved in light reception and synchronization
      of the circadian clock: (1) the compound eyes, (2) the ocelli, (3) the Hofbauer
      Buchner eyelets, (4) the blue-light photopigment cryptochrome, and (5) unknown
      photopigments in the clock-gene-expressing dorsal neurons. To understand the
      contributions of these photoreceptors and photopigments to synchronization, the
      authors monitored the flies' activity rhythms under artificial long and short
      days. They found that all the different photoreceptors and photopigments
      contribute significantly to entrainment under each photoperiod, but the compound
      eyes are especially important for entrainment to extreme photoperiods. The
      compound eyes are, furthermore, necessary for adjusting the phase of the activity
      rhythm, for distinguishing long days from constant light, and for the normal
      masking effects of light--namely, promotion of activity by lights-on and
      inhibition of activity by darkness. Cryptochrome is important for period
      lengthening under long days, although it is more important for entrainment to
      short days than to long days and is, furthermore, important for aftereffects of
      the photoperiod on the internal clock. The specific roles of the remaining
      photoreceptors are more difficult to assess.

PMID- 14582855
TI  - Olfactory bulbectomy modifies photic entrainment and circadian rhythms of body
      temperature and locomotor activity in a nocturnal primate.
AB  - Studies on rodents have emphasized that removal of the olfactory bulbs modulates
      circadian rhythmicity. Using telemetric recordings of both body temperature (Tb)
      and locomotor activity (LA) in a male nocturnal primate, the gray mouse lemur,
      the authors investigated the effects of olfactory bulbectomy on (1) the circadian
      periods of Tb and LA in constant dim light condition, and (2) photic re
      entrainment rates of circadian rhythms following 6-h phase shifts of entrained
      light-dark cycle (LD 12:12). Under free-running condition, bulbectomized males
      had significantly shorter circadian periods of Tb and LA rhythms than those of
      control males. However, the profiles of Tb rhythms, characterized by a phase of
      hypothermia at the beginning of the subjective day, and Tb parameters were not
      modified by olfactory bulbectomy. Under a light-dark cycle, olfactory bulbectomy
      significantly modified the expression of daily hypothermia, especially by an
      increase in the latency to reach minimal daily Tb, suggesting a delayed response
      to induction of daily hypothermia by light onset. Reentrainment rates following
      both a 6-h phase advance and a 6-h phase delay of entrained LD were also delayed
      in bulbectomized males. Olfactory bulbectomy led to significant fragmentation of
      locomotor activity and increased locomotor activity levels during the resting
      period. The shortening of circadian periods in bulbectomized males could partly
      explain the delayed responses to photic stimuli since in control males, the
      longer the circadian period, the better the response to light entrainment. This
      experiment shows for the 1st time that olfactory bulbs can markedly modify the
      circadian system in a primate.

PMID- 14582856
TI  - The circadian rhythm of the sex-pheromone-mediated behavioral response in the
      turnip moth, Agrotis segetum, is not controlled at the peripheral level.
AB  - The pheromone-mediated upwind flight of male turnip moths was observed in a
      flight tunnel at different times of day under conditions of a light-dark (LD)
      cycle, constant darkness (DD), and a shifted photoperiod. Under both LD and DD
      conditions, a significantly larger number of males flew to the pheromone during
      both the scotophase and the subjective scotophase than during the photophase and
      the subjective photophase for 2 consecutive days. When 1-day-old moths were
      transferred to a shifted LD cycle with lights turned off 4 h earlier, male
      behavioral responses to the pheromone advanced in time accordingly by 4 h. This
      showed that male behavioral responses to the pheromone are under the control of
      an endogenous oscillator. To further examine the level at which the circadian
      rhythm of the male behavioral response is regulated, the authors tested the
      olfactory responses of male antennal receptors to pheromone stimuli by means of
      electroantennograms (EAG) at different times of day. No significant variation in
      the sensitivity of the male antennal response to the pheromone was observed in
      terms of time of day. The results suggest that circadian regulation of the
      rhythmic behavioral response to pheromones in the male Agrotis occurs at the
      central nervous system level.

PMID- 14582857
TI  - Acute and phase-shifting effects of ocular and extraocular light in human
      circadian physiology.
AB  - Light can influence physiology and performance of humans in two distinct ways. It
      can acutely change the level of physiological and behavioral parameters, and it
      can induce a phase shift in the circadian oscillators underlying variations in
      these levels. Until recently, both effects were thought to require retinal light
      perception. This view was challenged by Campbell and Murphy, who showed
      significant phase shifts in core body temperature and melatonin using an
      extraocular stimulus. Their study employed popliteal skin illumination and
      exclusively considered phase-shifting effects. In this paper, the authors explore
      both acute effects and phase-shifting effects of ocular as well as extraocular
      light. Twelve healthy males participated in a within-subject design and received
      all of three light conditions--(1) dim ocular light/no light to the knee, (2) dim
      ocular light/bright extraocular light to the knee, and (3) bright ocular light/no
      light to the knee--on separate nights in random order. The protocol consisted of
      an adaptation night followed by a 26-h period of sustained wakefulness, during
      which a 4-h light pulse was presented at a time when maximal phase delays were
      expected. The authors found neither immediate nor phase-shifting effects of
      extraocular light exposure on melatonin, core body temperature (CBT), or
      sleepiness. Ocular bright-light exposure reduced the nocturnal circadian drop in
      CBT, suppressed melatonin, and reduced sleepiness significantly. In addition, the
      4-h ocular light pulse delayed the CBT rhythm by -55 min compared to the drift of
      the CBT rhythm in dim light. The melatonin rhythm shifted by -113 min, which
      differed significantly from the drift in the melatonin rhythm in the dim-light
      condition (-26 min). The failure to find immediate or phase-shifting effects in
      response to extraocular light in a within-subjects design in which effects of
      ocular bright light are confirmed strengthens the doubts raised by other labs of
      the impact of extraocular light on the human circadian system.

PMID- 14582858
TI  - The effects of low-dose 0.5-mg melatonin on the free-running circadian rhythms of
      blind subjects.
AB  - Exogenous melatonin (0.5-10 mg) has been shown to entrain the free-running
      circadian rhythms of some blind subjects. The aim of this study was to assess
      further the entraining effects of a daily dose of 0.5 mg melatonin on the
      cortisol rhythm and its acute effects on subjective sleep in blind subjects with
      free-running 6-sulphatoxymelatonin (aMT6s) rhythms (circadian period [tau] 24.23
      24.95 h). Ten subjects (9 males) were studied, aged 32 to 65 years, with no
      conscious light perception (NPL). In a placebo-controlled, single-blind design,
      subjects received 0.5 mg melatonin or placebo p.o. daily at 2100 h (treatment
      duration 26-81 days depending on individuals' circadian period). Subjective sleep
      was assessed from daily sleep and nap diaries. Urinary cortisol and aMT6s were
      assessed for 24 to 48 h weekly and measured by radioimmunoassay. Seven subjects
      exhibited an entrained or shortened cortisol period during melatonin treatment.
      Of these, 4 subjects entrained with a period indistinguishable from 24 h, 2
      subjects continued to free run for up to 25 days during melatonin treatment
      before their cortisol rhythm became entrained, and 1 subject appeared to exhibit
      a shortened cortisol period throughout melatonin treatment. The subjects who
      entrained within 7 days did so when melatonin treatment commenced in the phase
      advance portion of the melatonin PRC (CT6-18). When melatonin treatment ceased,
      cortisol and aMT6s rhythms free ran at a similar period to before treatment.
      Three subjects failed to entrain with initial melatonin treatment commencing in
      the phase delay portion of the PRC. During melatonin treatment, there was a
      significant increase in nighttime sleep duration and a reduction in the number
      and duration of daytime naps. The positive effect of melatonin on sleep may be
      partly due to its acute soporific properties. The findings demonstrate that a
      daily dose of 0.5 mg melatonin is effective at entraining the free-running
      circadian systems in most of the blind subjects studied, and that circadian time
      (CT) of administration of melatonin may be important in determining whether a
      subject entrains to melatonin treatment. Optimal treatment with melatonin for
      this non-24-h sleep disorder should correct the underlying circadian disorder (to
      entrain the sleep-wake cycle) in addition to improving sleep acutely.

PMID- 14582859
TI  - Thermochron ibuttons: an inexpensive method for long-term recording of core body
      temperature in untethered animals.

PMID- 14582860
TI  - Determinants of women's perceptions of risk in battering relationships.
AB  - Two studies have recently identified battered women's perceptions as a
      substantial predictor of reassault by their batterers. Only a few exploratory
      studies examine how women make these useful perceptions. We attempted to identify
      determinants of battered women's perceptions of reassault and safety using the 15
      month follow-up of a multisite evaluation of batterer intervention. The
      regression analyses indicate that the perceived likelihood of reassault increased
      with men who were divorced or separated, heavy drinkers, and severely abusive in
      the past. The strongest determinant for perceptions of safety was the perceived
      likelihood of reassault. Also, the women's professed reasons for their
      perceptions corresponded to the actual determinants. The women's perceptions
      appear, therefore, to be grounded in practical circumstances and correspond to
      establish predictors of reassault. Further research is needed to identify the
      additional cues, processes, or intuitions that make women's perceptions such a
      strong predictor of reassault.

PMID- 14582861
TI  - Male-initiated partner abuse during marital separation prior to divorce.
AB  - The purpose of this study was to assess predictors of male-initiated
      psychological and physical partner abuse during the separation process prior to
      divorce among a sample of 80 divorced fathers who reported no physical violence
      during their marriages. The predictor variables examined were male gender-role
      identity, female-initiated divorces, dependence on one's former wife, depression,
      anxiety, and coparental conflict. Through ordinary least square (OLS) regression
      techniques, it was found that male gender-role identity was positively related to
      male-initiated psychological abuse during separation. Logistic regression
      analyses revealed that male-initiated psychological abuse, anxiety level,
      coparental conflict, and dependence on one's former spouse increased the odds of
      a man engaging in physical abuse. However, depression decreased the odds of
      separation physical abuse. The models predicting both male-initiated
      psychological abuse (F = 2.20, p < .05, R2 = .15) and physical violence during
      the separation process were significant (Model chi2 = 35.00, df= 7, p < .001).

PMID- 14582862
TI  - Violence, coping, and mental health in a community sample of adolescents.
AB  - The current study examined the coping strategies, exposure to violence and
      psychological trauma symptoms of violent adolescents compared to less violent and
      nonviolent adolescents in a community sample. An anonymous self-report
      questionnaire was administered to students in six public high schools (grades 9
      12). The 10% most violent adolescents were identified and compared to their less
      violent and nonviolent peers. A total of 3724 students represented 68% of
      adolescents in all targeted schools. Ages ranged from 14 to 19 years; 52% were
      female; and 35% were African-American, 34% Caucasian and 23% Hispanic. Analyses
      revealed that violent adolescents compared to their less violent and nonviolent
      peers employed more maladaptive coping strategies, were exposed to higher levels
      of violence and reported higher clinical levels of psychological trauma symptoms.
      Maladaptive coping was also significantly associated with psychological trauma
      symptoms and violent behavior, even after controlling for the influence of
      demographic factors. The findings support the importance of appropriate
      identification, assessment and referral services for adolescents in nonclinical
      settings, and the role that coping strategies play in contributing to adolescent
      mental health and well-being.

PMID- 14582863
TI  - Social support as a mediator of revictimization of low-income African American
      women.
AB  - Mediating effects of social support on the link between childhood maltreatment
      and adult intimate partner violence (IPV) were explored in a sample of 362 low
      income, African American women. We examined relations between childhood
      maltreatment experiences (total maltreatment, sexual abuse, physical abuse,
      emotional abuse, emotional neglect, and physical neglect) and adult maltreatment
      (physical IPV and nonphysical IPV). Results of hierarchical multiple regression
      analyses revealed small, but significant, effects. Further, social support
      mediated revictimization. Social support fully mediated relations in which the
      form of childhood maltreatment was different than the form of adult IPV (e.g.,
      the relation between childhood sexual abuse and adult nonphysical IPV), but only
      partially mediated the relations in which the form of childhood maltreatment was
      similar to adult IPV (e.g., the relation between childhood emotional abuse and
      adult nonphysical IPV). Implications for clinical interventions for women with
      intimate partner violence experiences are discussed.

PMID- 14582864
TI  - Nonlethal intimate partner violence: examining race, gender, and income patterns.
AB  - The correlation between race of victim and intimate partner violence (IPV) is
      examined. Previous research showing a relationship between Black victims and
      higher levels of violence were based on uni-variate examinations and often do not
      consider other important factors. This paper presents national estimates of IPV
      by victim's race using the National Crime Victimization Survey (NCVS), 1993-1999.
      The estimates based only on race are then disaggregated to account for the
      victim's gender and household income. Uni-variate findings demonstrate that
      victim's race is significantly related to rates of intimate partner violence.
      However, after controlling for both victim's gender and annual household income,
      the victim's race is no longer significant. The importance of understanding
      intimate partner violence through a person's socioeconomic status rather than
      race is discussed.

PMID- 14582865
TI  - The short- and long-term effects of adolescent violent victimization experienced
      within the family and community.
AB  - Adolescents face high rates of victimization, yet little is known regarding the
      criminal consequences of these experiences. Using data from the National Youth
      Survey, this investigation compared the relative and combined effects of
      adolescent violent victimization perpetrated by family and nonfamily members on
      self-reported criminal offending from adolescence to early adulthood. The results
      demonstrate that both types of violence have an immediate and sustained impact on
      criminal involvement, although the effect is somewhat stronger for nonfamily
      victimization, and for both types, the relationship tends to weaken over time. In
      addition, those experiencing both types of victimization report a higher
      frequency of offending compared to those experiencing only one type. The findings
      indicate the need for prevention programs aimed at decreasing the prevalence of
      adolescent victimization, as well as intervention efforts to help victims from
      becoming offenders.

PMID- 14582866
TI  - Acute Stress Disorder in physical assault victims visiting a Danish emergency
      ward.
AB  - The purpose of this article is to assess the prevalence of Acute Stress Disorder
      (ASD) following violent assault in victims who come to the emergency ward, and
      compare the effects with degrees of injury. Two hundred and fourteen victims of
      violence completed a questionnaire 1 to 2 weeks after the assault. Measures
      included the Harvard Trauma Questionnaire, the Trauma Symptom Checklist and the
      Crisis Support Scale. RESULTS: Twenty-four percent met the full ASD diagnosis and
      21% a subclinical ASD diagnosis. Childhood sexual and physical abuse and shock
      due to a traumatic event that happened to someone close increased the likelihood
      of ASD four to ten times. Feeling of security and ability to express feelings
      reduced the likelihood of ASD by one-quarter, while feeling let down by others
      and hopelessness increased the likelihood of ASD respectively 1.4 and 2.6 times.

PMID- 14582867
TI  - Association between child sexual abuse and sexual revictimization in adulthood
      among women sex partners of injection drug users.
AB  - Community-recruited women (n = 1490) were interviewed about their early and adult
      sexual victimization histories to determine whether there was an association
      between child sexual abuse and adult revictimization by sex partners and
      strangers/nonsex partners. Adolescent sexual abuse, lifetime sex-trading, drug
      treatment, and mental health treatment were examined as mediating variables. One
      fourth of the women had been revictimized (i.e., experienced child sexual abuse
      and at least one instance of adult sexual victimization). Child sexual abuse was
      associated with both rape and other sexual victimization by a sex partner in
      adulthood, as well as adult rape by a stranger/nonsex partner. Drug and mental
      health treatments reduced abused women's chances of being raped by a sex partner;
      drug treatment also decreased the likelihood of other sexual victimization by a
      sex partner. Sex-trading increased abused women's likelihood of rape by a
      stranger or nonsex partner. Intervention--including drug treatment--can help
      women with child sexual abuse histories overcome some of the abuse-related
      sequelae that make them vulnerable to adult revictimization.

PMID- 14582868
TI  - Special report on the political and social contexts of health: Part I.
      Introduction: objectives and purposes of the study.
AB  - This article introduces a series of research projects (carried out by the
      International Network on Social Inequalities and Health) focused on the impact of
      politics on policy and the consequences for health and quality of life, an area
      that has been understudied in the social science literature. The introduction
      describes the conceptual model that guided the research, centered on the study of
      how political parties and social agents (such as trade unions) affect social
      inequalities and mortality indicators through labor market and welfare state
      policies. The major theme of this research is whether political and social
      interventions matter in health policy and health outcomes. The introduction also
      describes the different types of research projects carried out by the
      International Network at the national levels (among OECD countries) and at the
      regional and local levels (in the United Kingdom, Italy, Germany, Spain, and
      Sweden). This Journal issue presents the multinational study and the U.K. case
      study; the next issue will include the Italian, German, Spanish, and Swedish case
      studies and the summary and conclusions.

PMID- 14582869
TI  - The importance of the political and the social in explaining mortality
      differentials among the countries of the OECD, 1950-1998.
AB  - This article analyzes (within the conceptual frame defined in the previous
      article) the impact of political variables such as time of government by
      political parties (social democratic, Christian democratic or conservative,
      liberal, and ex-dictatorial that have governed the OECD countries during the 1950
      1998 period) and their electoral support on (1) redistributional policies in the
      labor market and in the welfare state; (2) the income inequalities measured by
      Theil and Gini indexes; and (3) health indicators, such as infant mortality and
      life expectancy. This analysis is carried out statistically by a bivariate and a
      multivariate analysis (a pooled cross-sectional study). Both analyses show that
      political variables play an important role in defining how public and social
      policies determine the levels of inequalities and affect the level of infant
      mortality. In general, political parties more committed to redistributional
      policies, such as social democratic parties, are the most successful in reducing
      inequalities and improving infant mortality. Less evidence exists, however, on
      effects on life expectancy. The article also quantifies statistically the
      relationship between the political and the policy variables and between these
      variables and the dependent variables--that is, the health indicators.

PMID- 14582870
TI  - Do social policies and political context matter for health in the United Kingdom?
AB  - This U.K. case study combines lessons from historical assessments with new
      empirical analyses of trends over the last decade to inform an appraisal of the
      impact of social actions on health. The empirical analyses examine life
      expectancy in the 354 local government councils in England by first identifying
      those that have better or worse health than expected fromtheir socioeconomic
      profile, and then selecting paired sets of "overachievers" and "underachievers"
      for more in-depth analysis. The findings taken as a whole provide evidence that
      social policies and political context do indeed matter for health. The historical
      material from the first industrial revolution, in particular, provides some of
      the most compelling evidence for this proposition. The empirical analyses over
      the last decade found a very powerful inverse association: the more deprived the
      local council, the lower the life expectancy of the population within that
      locality. However, even for the same level of deprivation and socioeconomic
      characteristics, some councils were doing much better than others in terms of
      health: for example, more than three years difference in life expectancy for
      carefully matched "urban fringe" councils. The article then examines the
      councils' political makeup and hence their likely policy perspective.

PMID- 14582871
TI  - An analysis of the role of health care in reducing socioeconomic inequalities in
      health: the case of the Netherlands.
AB  - The aim of this article is to analyze the role of the health care system in
      reducing socioeconomic inequalities in health in countries with good access to
      health services, using the Dutch example. In the past, health care has
      contributed substantially to reducing a number of health problems in the
      population, paticularly health problems leading to mortality. Data on trends in
      mortality from selected conditions by socioeconomic group show that both higher
      and lower socioeconomic groups have profited from these mortality reductions,
      probably because of largely equal access to essential health car services, and
      that absolute inequalities in mortality from these conditions have declined
      notably. The current situation is still one of largely equal financial access to
      health care services, with relatively small differences between socioeconomic
      groups in health care utilization, after adjustment for differences in prevalence
      of health problems. There is no evidence that inequalities in health care
      utilization contribute to a widening of socioeconomic inequalities in health.
      Financing of the health care system, however, is slightly regressive, and out-of
      pocket payments contribute to the poor financial situation of the chronically
      ill. For the future, three possible contributions of the health care system to
      reducing socioeconomic inequalities in health are described: preservation of
      equal access to high-quality health care; development of specific care packages
      for lower socioeconomic groups; promotion and support of intersectoral
      activities.

PMID- 14582872
TI  - The health of peoples: predicaments facing a reasoned utopia.
AB  - How might nations cooperate to improve the health of their most vulnerable
      peoples? There is, presently, no coherent political, social, or ethical framework
      to answer this question. What progress there is remains piecemeal. Despite a long
      term strategy to 2015 enshrining health as part of the process of human
      development--the Millennium Development Goals--existing institutions are
      struggling to meet these challenges. The WHO is underfunded and its work in
      countries is weak. The World Bank is rich but remains unable to free itself from
      a neoliberal Washington consensus. New institutions--such as the Global Fund to
      Fight AIDS, Tuberculosis, and Malaria--distort efforts to build a coordinated
      international strategy for global health. And major policy initiatives (e.g., the
      Commission on Macroeconomics and Health) lack political commitment to invest in
      health. In this article, the author traces the beginnings of an answer to the
      question of what might constitute a political (specifically, foreign policy)
      approach to improving the health of peoples. A normative model for defining a
      just health system is urgently required. The author uses the framework of
      international relations provided by John Rawls to devise a series of policy
      principles for the health of peoples.

PMID- 14582873
TI  - Sex and gender: the challenges for epidemiologists.
AB  - Gender issues are now receiving more attention on global and national health
      agendas. However, the evidence base for policy and practice in this area remains
      limited and conceptual confusion is still common. This article reviews the
      challenges facing epidemiologists and other researchers who aim to make their
      work more "gender sensitive." It begins by exploring the concepts of biological
      "sex" and social "gender" and assesses their implications for the health of both
      women and men. It then reviews a range of strategies for mainstreaming sex and
      gender into health research. The article concludes with brief comments on the
      links between gender equity and wider equality concerns.

PMID- 14582874
TI  - Globalization and the pharmaceutical industry revisited.
AB  - This survey of the pharmaceutical industry at the beginning of the 21st century
      updates some of the information provided in Claudio Tarabusi and Graham Vickery's
      survey, "Globalization in the Pharmaceutical Industry," published in the
      International Journal of Health Services in 1998, which was largely based on data
      up to 1993. However, the purpose of the present article differs from that of
      Tarabusi and Vickery, which covered a wide range of aspects of the industry
      relevant to globalization but did not explicitly address the question of the
      extent to which the industry could be described as globalized. After looking at
      the industry in some detail, the author directly confronts the question of the
      appropriateness of the use of the term "globalization" for characterizing the
      directions in which the pharmaceutical industry has been moving.

PMID- 14582875
TI  - Uneven health outcomes and political resistance under residual neoliberalism in
      Africa.
AB  - Africa has suffered two decades of policy implementation associated with the
      "neoliberal" macroeconomic as well as micro-development paradigm, and the health
      status of this continent has deteriorated markedly. Notwithstanding the
      discrediting of such policies since the late 1990s, they continue to be applied
      in Africa, especially by the World Bank and IMF, through Poverty Reduction
      Strategy Papers and the Highly Indebted Poor Countries debt relief initiative.
      Evidence can be found in the inadequate fiscal allocations to the health sector;
      the inadequate conceptualization of health in relation to other sectors;
      insufficient consultation with civil society; ongoing implementation of cost
      recovery and user-fee provisions; a failed strategy to access pharmaceutical
      products, by respecting unnecessary Trade in Intellectual Property Rights
      provisos; and, most importantly, glaring insufficiencies in reducing Africa's
      foreign debt. One reflection of the balance of forces between Washington
      financial agencies and African societies is the adoption of the New Partnership
      for Africa's Development at the urging of the South African and Nigerian
      governments. While the WHO has helped to research, publicize, and criticize the
      problems associated with durable neoliberalism in African health care, it also
      continues to make serious mistakes as it remains locked within the paradigm. A
      human rights perspective being developed by the African Social Forum is, in
      contrast, consistent with broader international trends in the opposition to
      corporate globalization.

PMID- 14582876
TI  - Calculation of the Pitot tube correction factor for Newtonian and non-Newtonian
      fluids.
AB  - This paper presents the numerical investigation performed to calculate the
      correction factor for Pitot tubes. The purely viscous non-Newtonian fluids with
      the power-law model constitutive equation were considered. It was shown that the
      power-law index, the Reynolds number, and the distance between the impact and
      static tubes have a major influence on the Pitot tube correction factor. The
      problem was solved for a wide range of these parameters. It was shown that
      employing Bernoulli's equation could lead to large errors, which depend on the
      magnitude of the kinetic energy and energy friction loss terms. A neural network
      model was used to correlate the correction factor of a Pitot tube as a function
      of these three parameters. This correlation is valid for most Newtonian,
      pseudoplastic, and dilatant fluids at low Reynolds number.

PMID- 14582877
TI  - Real-time analysis system for gas turbine ground test acoustic measurements.
AB  - This paper provides an overview of a data system upgrade to the Pratt and Whitney
      facility designed for making acoustic measurements on aircraft gas turbine
      engines. A data system upgrade was undertaken because the return-on-investment
      was determined to be extremely high. That is, the savings on the first test
      series recovered the cost of the hardware. The commercial system selected for
      this application utilizes 48 input channels, which allows either 1/3 octave
      and/or narrow-band analyses to be preformed real-time. A high-speed disk drive
      allows raw data from all 48 channels to be stored simultaneously while the
      analyses are being preformed. Results of tests to ensure compliance of the new
      system with regulations and with existing systems are presented. Test times were
      reduced from 5 h to 1 h of engine run time per engine configuration by the
      introduction of this new system. Conservative cost reduction estimates for future
      acoustic testing are 75% on items related to engine run time and 50% on items
      related to the overall length of the test.

PMID- 14582878
TI  - Instrumentation used to measure residential magnetic fields and currents.
AB  - The equipment used to measure magnetic fields and electric currents in residences
      is described. The instrumentation consisted of current transformers, magnetic
      field probes and locally designed and built signal conditioning modules. The data
      acquisition system was capable of unattended recording for extended time periods.
      The complete system was calibrated to verify its response to known physical
      inputs.

PMID- 14582879
TI  - A task scheduler framework for self-powered wireless sensors.
AB  - The cost and inconvenience of cabling is a factor limiting widespread use of
      intelligent sensors. Recent developments in short-range, low-power radio seem to
      provide an opening to this problem, making development of wireless sensors
      feasible. However, for these sensors the energy availability is a main concern.
      The common solution is either to use a battery or to harvest ambient energy. The
      benefit of harvested ambient energy is that the energy feeder can be considered
      as lasting a lifetime, thus it saves the user from concerns related to energy
      management. The problem is, however, the unpredictability and unsteady behavior
      of ambient energy sources. This becomes a main concern for sensors that run
      multiple tasks at different priorities. This paper proposes a new scheduler
      framework that enables the reliable assignment of task priorities and scheduling
      in sensors powered by ambient energy. The framework being based on environment
      parameters, virtual queues, and a state machine with transition conditions,
      dynamically manages task execution according to priorities. The framework is
      assessed in a test system powered by a solar panel. The results show the
      functionality of the framework and how task execution reliably is handled without
      violating the priority scheme that has been assigned to it.

PMID- 14582880
TI  - Software sensors for bioprocesses.
AB  - State estimation is a significant problem in biotechnological processes, due to
      the general lack of hardware sensor measurements of the variables describing the
      process dynamics. The objective of this paper is to review a number of software
      sensor design methods, including extended Kalman filters, receding-horizon
      observers, asymptotic observers, and hybrid observers, which can be efficiently
      applied to bioprocesses. These several methods are illustrated with simulation
      and real-life case studies.

PMID- 14582881
TI  - Autotuning of a new PI-PD Smith predictor based on time domain specifications.
AB  - The paper extends a recent work on a modified PI-PD Smith predictor, which leads
      to significant improvements in the control of processes with large time constants
      or an integrator or unstable plant transfer functions plus long dead time for
      reference inputs and disturbance rejections. Processes with high orders or long
      time delays are modeled with lower order plant transfer functions with longer
      time delays. The PI-PD controller is designed so that the delay-free part of the
      system output will follow the response of a first-order plant or second-order
      plant, where it is appropriate, assuming a perfect matching between the actual
      plant and model in both the dynamics and time delay. The provided simple tuning
      formulas have physically meaningful parameters. Plant model transfer functions
      and controller settings are identified based on exact analysis from a single
      relay feedback test using the peak amplitude and frequency of the process output.
      Examples are given to illustrate the simplicity and superiority of the proposed
      method compared with some existing ones.

PMID- 14582882
TI  - On-line lower-order modeling via neural networks.
AB  - This paper presents a novel method to determine the parameters of a first-order
      plus dead-time model using neural networks. The outputs of the neural networks
      are the gain, dominant time constant, and apparent time delay. By combining this
      algorithm with a conventional PI or PID controller, we also present an adaptive
      controller which requires very little a priori knowledge about the plant under
      control. The simplicity of the scheme for real-time control provides a new
      approach for implementing neural network applications for a variety of on-line
      industrial control problems. Simulation and experimental results demonstrate the
      feasibility and adaptive property of the proposed scheme.

PMID- 14582883
TI  - Robust stability of some oscillatory systems including time-varying delay with
      applications in congestion control.
AB  - This paper focuses on the stability of some second-order linear systems with
      multiple constant and time-varying delays, under the assumption that the
      corresponding system without delays is an oscillator. Sufficient conditions for
      delay-dependent stability will be derived using the integral quadratic constraint
      approach combined with the generalized eigenvalue distribution of some
      appropriate finite-dimensional matrix pencils. As applications, we shall discuss
      some fluid approximation models used in congestion control of high-speed
      networks, under the natural assumptions that the control-time intervals are
      constant, but the round-trip times are time-varying.

PMID- 14582884
TI  - Periodic speed ripples minimization in PM synchronous motors using repetitive
      learning variable structure control.
AB  - In this paper, we propose a simple repetitive learning variable structure control
      (RLVSC) scheme to reduce periodic speed ripples in a permanent magnet synchronous
      motor (PMSM). These speed ripples are induced by parasitic torque pulsations that
      vary periodically with rotor position. The conventional PI speed controller is
      able to reduce speed ripples to a certain extent but not sufficient enough for
      many high performance applications. During steady state, the RLVSC generates a
      reference compensation current that together with the outer loop PI speed
      controller is used to minimize the speed ripples. Being a plug-in module, the
      proposed RLVSC controller can be easily integrated to any of the existing PMSM
      drive systems. Experimental evaluation of the proposed scheme is carried out on a
      DSP-controlled PMSM drive platform. Test results obtained demonstrate the
      effectiveness of the proposed control scheme in reducing speed ripples by a
      factor of approximately 3 under various operating conditions.

PMID- 14582885
TI  - Simulating thermal power plant processes on a message passing environment.
AB  - Simulators play a very important role in the operation of thermal power plants
      and also in the design of control systems for these plants. To cater to this
      requirement elaborate methodologies have been developed to simulate thermal power
      plant processes in an interactive way. Due to the intensive computations
      involved, such simulators use one or more high through-put computers known as the
      simulation computers. This paper puts forward a method where parallel processing
      on a low latency message passing environment has been used to simulate thermal
      power plant processes following a modular approach. This eliminates the need of
      an expensive high through-put simulation computer, thus cutting down the hardware
      cost associated with a simulator and increasing the system reliability manifold.

PMID- 14582886
TI  - Process control of product quality.
AB  - This paper describes a method to control output product quality (product
      variability) by applying engineering or automatic process control (APC) and
      statistical process control (SPC) techniques. APC techniques have been used to
      control process variables such as feed rate, temperature, pressure, viscosity,
      and to product quality variables as well. SPC techniques have also been applied
      to control product quality. APC and SPC techniques overlap at the interface of
      the two process control methodologies. It is possible to produce material of
      desired quality by having an acceptable level of variation in the measured output
      characteristics. APC aims to maintain certain key process variables as near their
      set points for as much of the time as possible. There are situations in process
      control where some form of feedback control is necessary and yet where stability
      cannot be easily attained in the feedback control loop. Disturbance (noise)
      afflicts a process, which together with issues of dynamics and dead time (time
      delay) compounds the process control problem. The process control practitioner
      faces a challenge while tackling issues of process delay (dead time) and dynamics
      (inertia). Process control of product variability (control error standard
      deviation) is possible by developing and simulating a feedback control algorithm
      for dead-time processes. It is quite common to encounter problems connected with
      feedback (closed-loop) control stability, controller limitations, and dead-time
      compensation to obtain minimum variance (mean square error) control at the
      output. Details of a method to control the quality of a product at output by
      applying statistical process monitoring and feedback control adjustment are
      presented in this paper. The focus of this paper is on the issues of process
      delay ("dead time") and dynamics ("inertia") at the interface between SPC and APC
      to control output product quality.

PMID- 14582887
TI  - A fault detection and isolation filter for discrete linear systems.
AB  - The problem of fault and/or abrupt disturbances detection and isolation for
      discrete linear systems is analyzed in this work. A strategy for detecting and
      isolating faults and/or abrupt disturbances is presented. The strategy is an
      extension of an already existing result in the continuous time domain to the
      discrete domain. The resulting detection algorithm is a Kalman filter with a
      special structure. The filter generates a residuals vector in such a way that
      each element of this vector is related with one fault or disturbance. Therefore
      the effects of the other faults, disturbances, and measurement noises in this
      element are minimized. The necessary stability and convergence conditions are
      briefly exposed. A numerical example is also presented.

PMID- 14582888
TI  - Fault detection and classification in chemical processes based on neural networks
      with feature extraction.
AB  - Feed forward neural networks are investigated here for fault diagnosis in
      chemical processes, especially batch processes. The use of the neural model
      prediction error as the residual for fault diagnosis of sensor and component is
      analyzed. To reduce the training time required for the neural process model, an
      input feature extraction process for the neural model is implemented. An
      additional radial basis function neural classifier is developed to isolate faults
      from the residual generated, and results are presented to demonstrate the
      satisfactory detection and isolation of faults using this approach.

PMID- 14582889
TI  - Safety analysis of the waterwall in one PFBC boiler by dynamic model.
AB  - With the help of a dynamic mathematical model, the differential pressure across
      the waterwall in a PFBC (pressurized fluidized bed combustion) boiler is analyzed
      under abnormal conditions. The simulation tests have shown that the differential
      pressure will exceed design specification when the bursting diaphragm at the
      outlet pipe of the freeboard is ruptured and its capacity is larger than 50% of
      the flue gas flow rate of the boiler.

PMID- 14582890
TI  - Basic mechanisms of lung inflammation: executive summary of the first Lung
      Science Meeting of the European Respiratory Society at Taormina, Italy in 2003.

PMID- 14582891
TI  - Oxidative stress as an initiator of cytokine release and cell damage.
AB  - This article characterised the role of oxidative stress in mediating pathological
      reactions in the lung and the unique antioxidant defences that the lung
      possesses. The impact of redox balance in regulating inflammatory and immune
      reactions were discussed, and the impact of enhancing lung antioxidant capacity
      in animal models of asthma and chronic obstructive pulmonary disease were
      characterised.

PMID- 14582892
TI  - Epithelial apoptosis in the initiation of lung fibrosis.

PMID- 14582893
TI  - How T-lymphocytes are activated and become activators by cell-cell interaction.

PMID- 14582894
TI  - Inhibition of signal transduction pathways involved in inflammation.

PMID- 14582895
TI  - Targeting apoptosis in the control of inflammation.

PMID- 14582896
TI  - Acute lung injury: how the lung inflammatory response works.

PMID- 14582897
TI  - Mechanisms of airway epithelial damage: epithelial-mesenchymal interactions in
      the pathogenesis of asthma.

PMID- 14582898
TI  - Proteolysis in the lung.

PMID- 14582899
TI  - Role of coagulation cascade proteases in lung repair and fibrosis.

PMID- 14582901
TI  - Inflammation and respiratory disease. Proceedings of the 1st ERS Lung Science
      Conference. Taormina, Italy, March 28-30, 2003.

PMID- 14582900
TI  - Matrix metalloproteinases in lung repair.

PMID- 14582902
TI  - The pharmacoepidemiology of COPD: recent advances and methodological discussion.

PMID- 14582903
TI  - Lung volume reduction surgery: what can we learn from the National Emphysema
      Treatment Trial?

PMID- 14582904
TI  - Evaluating the effects of stress on asthma: a paradoxical challenge.

PMID- 14582905
TI  - Flexible bronchoscopy in children: an open airway.

PMID- 14582906
TI  - Exosomes with major histocompatibility complex class II and co-stimulatory
      molecules are present in human BAL fluid.
AB  - Exosomes are 30-100 nm diameter vesicles formed by inward budding of endosomal
      compartments and are produced by several cell types, including T-cells, B-cells
      and dendritic cells (DC)s. Exosomes from DCs express major histocompatibility
      complexes (MHC) class I and II, and co-stimulatory molecules on their surface,
      and can induce antigen-specific activation of T-cells. The aims of the present
      study were to investigate for the presence of exosomes in bronchoalveolar lavage
      fluid (BALF) from healthy individuals, and to establish if these exosomes bear
      MHC and co-stimulatory molecules. The authors analysed BALF taken from seven
      healthy volunteers and used exosomes from monocyte-derived DC (MDDC) cultures as
      a reference. After ultracentrifugation, exosomes were bound to anti-MHC class II
      coated magnetic beads and analysed by flow cytometry and electron microscopy. The
      authors report for the first time that exosomes are present in BALF. These
      exosomes are similar to MDDC derived exosomes as they express MHC class I and II,
      CD54, CD63 and the co-stimulatory molecule CD86. The results demonstrate that
      exosomes are present in the lung, and since they contain both major
      histocompatibility complex and co-stimulatory molecules it is likely that they
      are derived from antigen presenting cells and might have a regulatory role in
      local immune defence.

PMID- 14582907
TI  - Short-burst oxygen immediately before and after exercise is ineffective in
      nonhypoxic COPD patients.
AB  - Short-burst oxygen therapy (SBOT) remains an unproven treatment for reduction of
      exertional dyspnoea in chronic obstructive pulmonary disease (COPD). This study
      aimed to assess whether SBOT before exercise reduces dyspnoea or improves
      performance, and whether SBOT after exercise reduces dyspnoea during recovery.
      Twenty-two clinically stable COPD patients (mean forced expiratory volume in one
      second 34% predicted, mean resting saturation 94%) attended a respiratory
      gymnasium and undertook four 6-min walk (6MW) tests at each of two sessions, 1
      week apart. Cylinder air or oxygen was administered single-blind in random order
      for 5 min prior to the first two 6MW and during recovery following the final two
      6MW. Dyspnoea was self-rated by subjects using the modified Borg scale. There was
      no significant difference in mean 6MW distance or final Borg score for air and
      oxygen given before exercise. There was also no significant difference in mean
      time-to-resting Borg score for air and oxygen given after exercise. Only two
      subjects demonstrated a clinically significant and consistent reduction in
      dyspnoea for oxygen compared with air either before or after exercise. Overall,
      short-burst oxygen therapy neither reduced dyspnoea nor improved performance.
      This study does not support the use of short-burst oxygen therapy either
      immediately before or after exercise.

PMID- 14582908
TI  - Diagnostic tools in tuberculous pleurisy: a direct comparative study.
AB  - Thoracoscopy is the most accurate yet most expensive tool for establishing the
      diagnosis of tuberculous (TB) pleurisy. However, most high TB-incidence regions
      have limited financial resources, lack the infrastructure needed for routine
      thoracoscopy and require an alternative, cost-effective diagnostic approach for
      pleural effusions. Altogether, 51 patients with undiagnosed exudative pleural
      effusions were recruited for a prospective, direct comparison between bronchial
      wash, pleural fluid microbiology and biochemistry (adenosine deaminase (ADA) and
      cell count), closed needle biopsy, and medical thoracoscopy. The final diagnosis
      was TB in 42 patients (82%), malignancy in five (10%) and idiopathic in four
      patients (8%). Sensitivity of histology, culture and combined histology/culture
      was 66, 48 and 79%, respectively for closed needle biopsy and 100, 76 and 100%,
      respectively for thoracoscopy. Both were 100% specific. Pleural fluid ADA of > or
      = 50 U x L(-1) was 95% sensitive and 89% specific. Combined ADA,
      lymphocyte/neutrophil ratio > or = 0.75 plus closed needle biopsy reached 93%
      sensitivity and 100% specificity. A combination of pleural fluid adenosine
      deaminase, differential cell count and closed needle biopsy has a high diagnostic
      accuracy in undiagnosed exudative pleural effusions in areas with high incidences
      of tuberculosis and might substitute medical thoracoscopy at considerably lower
      expense in resource-poor countries.

PMID- 14582909
TI  - Surfactant protein D in serum from patients with allergic bronchopulmonary
      aspergillosis.
AB  - Surfactant protein D (SP-D) interacts with Aspergillus fumigatus and is strongly
      increased in the lavage from animals with acute allergic reactions to the fungus,
      suggesting a central role for SP-D. As the course of cystic fibrosis (CF) is
      often complicated by an allergic bronchopulmonary aspergillosis (ABPA), the
      authors hypothesised that SP-D may also be increased in serum during an ABPA,
      potentially assisting in its diagnosis and follow-up. In 22 patients with CF (11
      with ABPA, 11 matched without ABPA) and 19 control patients without a pulmonary
      disease, SP-D concentrations in serum were assessed by an enzyme immunoassay.
      Serum SP-D in CF patients (130 +/- 16 ng x mL(-1) (mean +/- SEM)) was
      significantly higher than in the controls without lung disease (66 +/- 8 ng x mL(
      1)). During the whole ABPA-episode, SP-D level did not change significantly,
      despite large changes of total serum immunoglobulin E. There was a clear negative
      correlation between SP-D concentration and overall lung function, i.e. forced
      expiratory volume in one second and forced vital capacity. Serum level of
      surfactant protein D may be of value to follow pulmonary function and lung injury
      in cystic fibrosis patients. Surfactant protein D serum levels are not helpful
      for the diagnosis and follow-up of an allergic bronchopulmonary aspergillosis
      episode, contrary to what was expected from animal experiments.

PMID- 14582911
TI  - Interleukin-13 and -4 expression in the central airways of smokers with chronic
      bronchitis.
AB  - The aim of this study was to determine whether the T-helper 2-type cytokines
      interleukin (IL)-13 and -4 are involved in mucus hypersecretion, the hallmark of
      chronic bronchitis (CB). Surgical specimens were examined from 33 subjects
      undergoing lung resection for localised peripheral malignant pulmonary lesions:
      21 smokers with symptoms of CB, 10 asymptomatic smokers (AS) and two nonsmokers
      with normal lung function. The number of IL-4 and -13 positive (+) cells in the
      central airways was quantified. To better assess the cytokine profile, a count
      was also made of IL-5+ and interferon (IFN)-gamma+ cells. Compared to AS, the CB
      group had an increased number of IL-13+ and -4+ cells in the bronchial submucosa,
      while the number of IL-5+ and IFN-gamma+ cells were similar in all the groups. No
      significant associations were found between the number of cells expressing IL-13
      or -4 and the number of inflammatory cells. Double labelling showed that 13.2 and
      12.9% of IL-13+ cells were also CD8+ and CD4+, whereas 7.5 and 5% of IL-4+ cells
      were CD8+ and CD4+, respectively. In conclusion, T-helper-2 and -1 protein
      expression is present in the central airways of smokers and interleukin-4 and -13
      could contribute to mucus hypersecretion in chronic bronchitis.

PMID- 14582910
TI  - Substance P-induced pulmonary vascular remodelling in precision cut lung slices.
AB  - Substance P (SP) levels have been reported to be elevated in animal models of
      pulmonary hypertension (PH) and chronic administration of SP has been shown to
      induce PH. In the present study, the role of reactive oxygen species (ROS) as
      mediators of SP-induced vascular remodelling and PH was analysed. Vascular
      remodelling was induced in precision cut lung slices by treatment with
      [Sar9,Met11(O2)]-SP and by hypoxia. Functional analyses were used to study the
      chronic [Sar9,Met11(O2)]-SP-mediated effects on proliferation and generation of
      ROS, which is involved in the pathogenesis of PH. The nonpeptide NK-1 receptor
      antagonist CP 96345 was used to block [Sar9,Met11(O2)]-SP effects. ROS generation
      and proliferation was assayed by the dichloroflourescein-diacetate method and
      incorporation of 5-Bromo-2'-Deoxyuridine, respectively. ROS generation was
      induced by either 1% oxygen (5.8-fold) or [Sar9,Met11(O2)]-SP (8-fold) in
      normoxia in the alveolar region. [Sar9,Met11(O2)]-SP did not further elevate ROS
      levels in hypoxia, suggesting an oxygen-dependent mechanism. High ROS levels
      stabilised hypoxia inducible factor-1alpha and induced proliferation in small
      vessels (4.3-fold in hypoxia and [Sar9,Met11(O2)]-SP). Both ROS generation and
      proliferation were blocked in the presence of CP 96345, nitroblue-tetrazolium, N
      acetylcysteine- and diphenylene-iodonium. The results presented in this study
      indicate a role of SP in proliferative events associated with vascular
      remodelling in pulmonary hypertension.

PMID- 14582912
TI  - Imbalance between vascular endothelial growth factor and endostatin in emphysema.
AB  - Vascular endothelial growth factor (VEGF) stimulates endothelial cell
      proliferation, and endostatin directly antagonises the biological effects of
      VEGF. The maintenance of pulmonary endothelial cells is also thought to depend
      upon the local balance of VEGF and endostatin in the lung. Therefore, this study
      was designed to determine whether there is an imbalance between VEGF and
      endostatin levels in patients with pulmonary emphysema. VEGF and endostatin
      levels were simultaneously measured from 25 emphysema patients and 12 normal
      control subjects, and their correlation and balance in induced sputum was
      evaluated. VEGF levels in induced sputum were significantly lower in emphysema
      patients (854 +/- 307 pg x mL(-1)) than in normal controls (1,791 +/- 1,192 pg x
      mL(-1)). In contrast, there was no significant difference in endostatin levels
      among the two groups. Therefore, the ratio of VEGF to endostatin levels was
      markedly lower in emphysema patients (4.5 +/- 1.8) than in normal controls (8.1
      +/- 2.6). Moreover, VEGF levels were correlated with endostatin levels in normal
      controls but not in emphysema patients. In addition, the ratio of VEGF to
      endostatin levels was correlated with forced expiratory volume in one second
      (FEV1), FEV1/forced vital capacity and carbon monoxide diffusing capacity of the
      lung in emphysema patients. The findings in this study suggest that there is an
      imbalance between vascular endothelial growth factor and endostatin levels in
      induced sputum from emphysema patients.

PMID- 14582913
TI  - Early pulmonary response to allergen is attenuated during acute emotional stress
      in females with asthma.
AB  - Some asthma patients and physicians who treat asthma have reported that stress
      worsens their disease. It has also recently been shown that chronic stressful
      life events increase airway inflammation 6-24 h after inhalation of antigen in
      patients with allergic asthma. However, there is no data regarding the effect of
      an acute stressor on the airway constriction that occurs within minutes of
      antigen inhalation (early pulmonary response) in this same population. The aim of
      this study was to examine this effect in eight females with allergic asthma. Each
      subject was challenged with increasing concentrations of inhaled allergen on a
      control visit (no stress) and on a stress visit, when they were asked to verbally
      recount an emotionally stressful situation between each concentration. Systolic
      (SP) and diastolic (DP) blood pressure, cardiac frequency (fC) and forced
      expiratory volume in one second (FEV1) were measured on both visits. SP, DP and
      fC were statistically increased on the stress visit as compared to control. Per
      cent decrease in FEV1 at the same last dose of allergen was significantly less on
      the stress visit (11.2 +/- 7.0%) compared to control (15.0 +/- 8.7%). These
      findings suggest that the early pulmonary response to inhaled allergen is
      attenuated while verbally re-experiencing an acute emotional stressor in females
      with allergic asthma.

PMID- 14582914
TI  - Individual and area-based indicators of socioeconomic status and childhood
      asthma.
AB  - The current study evaluated the association between individual and area-based
      indicators of socioeconomic status and the prevalence, severity, and lifetime
      hospitalisation for asthma in children. The representative sample of 4,027
      children from Rome, aged 6-7 yrs, used for the 1994 ISAAC (International Study on
      Asthma and Allergies in Childhood) initiative, was selected. Individual and small
      area indicators of socioeconomic status were used. Individual data on parents'
      education and on childhood asthma were gathered from self-administered parental
      questionnaires. Two small-area indicators (socioeconomic status index (SES) and
      average income in 1994) were derived using information available at the census
      tract of residence. Logistic regression models were used to estimate the
      association of parental education and small area indicators with asthma
      prevalence, severity, and hospitalisation. Parental smoking was considered in the
      analysis as a potential confounder. Prevalence of physician diagnosis of asthma
      (11.3%) increased as father's education decreased. Prevalence of severe asthma
      (1.6%) increased as maternal and paternal educational levels decreased. Lifetime
      hospitalisation for asthma (2.8%) was strongly associated with both parental
      education and small-area indicators of social disadvantage, even when considered
      simultaneously in the same logistic model. Socioeconomic conditions are
      associated with asthma occurrence, its severity, and hospitalisation. The
      association was stronger for asthma severity and hospitalisation. Individual
      indicators correlated better with the outcomes than area-based indicators.
      However, living in an underprivileged area is a strong independent predictor of
      hospital admission for asthma.

PMID- 14582915
TI  - Unaltered respiratory-related evoked potentials after acute diaphragm dysfunction
      in humans.
AB  - Respiratory muscles play an important role in the origin of respiratory
      sensations. Data dissecting the role of the diaphragm and other inspiratory
      muscles are scarce. This study aimed to determine the impact of diaphragm
      dysfunction following inspiratory resistive loading on respiratory-related evoked
      potentials considered as a neurophysiological substrate of certain types of
      respiratory sensations. Altogether, nine subjects aged 25-50 yrs (six females)
      participated in the study. Transdiaphragmatic pressure output of cervical
      magnetic stimulation (with subdivision in oesophageal and gastric component), and
      respiratory-related evoked potentials (C3 and C4 derivations in the international
      10-20 system) following mid-inspiratory occlusions were studied before and after
      an inspiratory-resistive loading challenge. Predominant diaphragm dysfunction was
      observed in seven subjects (average 28% reduction in transdiaphragmatic pressure,
      from 27.25-19.91 cmH2O, with increased oesophageal-to-gastric pressure ratio).
      The latencies and amplitudes of all the components of the respiratory-related
      evoked potentials were unchanged. The study concluded that predominant diaphragm
      fatigue does not affect respiratory-related evoked potentials.

PMID- 14582916
TI  - Long-term noninvasive ventilation in children and adolescents with neuromuscular
      disorders.
AB  - The aim of the current study was to investigate the long-term impact of nocturnal
      noninvasive (positive-pressure) ventilation (NIV) on sleep, sleep-disordered
      breathing (SDB) and respiratory function in children and adolescents with
      progressive neuromuscular disorders (NMD). Thirty patients (12.3 +/- 4.1 yrs)
      with various inherited NMD were treated with NIV for ventilatory insufficiency
      (n=14) or symptomatic SDB (n=16). Patients were prospectively followed with sleep
      studies, spirometry and peak inspiratory muscle pressure. Ten patients were
      studied before and after 3 nights withdrawal from NIV. NIV normalised nocturnal
      gas exchange in all patients and diurnal gas exchange in patients with
      ventilatory insufficiency. The effects persisted over 25.3 +/- 12.7 months.
      Nocturnal transcutaneous partial pressure of carbon dioxide improved from
      (baseline versus latest control) 7.1 +/- 1.3 to 5.5 +/- 0.6 kPa (53.7 +/- 9.9 to
      41.6 +/- 4.8 mmHg), diurnal carbon dioxide arterial tension from 6.3 +/- 1.6 to
      5.4 +/- 0.5 kPa (47.5 +/- 11.9 to 40.6 +/- 3.6 mmHg). NIV improved respiratory
      disturbance index, arousals from sleep, nocturnal heart rate and sleep
      architecture. Vital capacity decreased in five adolescents with Duchenne muscular
      dystrophy -183 +/- 111 mL x yr(-1) but remained stable in 25 children with other
      conditions (8 +/- 78 mL x yr(-1)). Three nights withdrawal of NIV in 10
      previously stable patients resulted in prompt deterioration of SDB and gas
      exchange back to baseline but could be instantly normalised by resumption of NIV.
      Noninvasive (positive-pressure) ventilation has favourable long-term impact on
      nocturnal and diurnal gas exchange and sleep and in patients with non-Duchenne
      neuromuscular disorders on vital capacity as well. It is indicated in children
      and adolescents with symptomatic sleep-disordered breathing or ventilatory
      insufficiency due to neuromuscular disorders.

PMID- 14582917
TI  - Risk factors for recent transmission of Mycobacterium tuberculosis.
AB  - In recent decades, the decline of tuberculosis has stopped in Western Europe,
      mainly due to increased immigration from high-prevalence countries. The objective
      of the current study was to identify risk factors for developing tuberculosis
      following recent infection, in order to better target interventions. Strains from
      861 culture-positive cases, diagnosed in Norway in 1994-1999, were analysed by
      use of restriction fragment length polymorphism (RFLP). A cluster was defined as
      two or more isolates with identical RFLP patterns. Risk factors for being part of
      a cluster were identified by univariate and multivariate analysis. A total of 134
      patients were part of a cluster. These constituted 5% Asian-born, 18% Norwegian
      born, 24% European-born and 29% African-born patients. Four independent risk
      factors for being part of a cluster were identified: being born in Norway, being
      of young age, being infected with an isoniazid-resistant strain and being
      infected with a multidrug-resistant strain. Transmission of tuberculosis may be
      further reduced by improving case management, contact tracing, preventive
      treatment, screening of immigrants and access to health services for the foreign
      born population.

PMID- 14582918
TI  - Duration of length of stay in pneumonia: influence of clinical factors and
      hospital type.
AB  - Length of stay (LOS) in hospital for community-acquired pneumonia depends on the
      characteristics of the patient and hospital. The present study sought to identify
      these variables within the first 24 h of hospitalisation. Patients hospitalised
      for pneumonia in four hospitals (one teaching and three general hospitals) had
      their data analysed by univariate and multivariate statististics. The variables
      entered were LOS, demographical characteristics, referral source, comorbidity,
      initial severity of illness, laboratory analyses, initial radiograph findings and
      antibiotic treatment regimens. The study sample included 425 patients. The
      overall mortality was 8.2% and the median LOS was 9 days. Using LOS as a
      dependent variable, three multivariate linear regression analyses were performed
      with: 1) the whole cohort; 2) the low-risk classes (categories I and II of Fine);
      and 3) the high-risk classes (categories III, IV and V of Fine). The mathematical
      model identified hypoxemia, low diastolic pressure, pleural effusion, multi-lobe
      involvement and hypoalbuminaemia as associated with longer stays in risk classes
      III-V, while in the low-risk patients (I-II) only hypoxemia and pleural effusion
      appeared in the equation. Following adjustment for these clinical variables, the
      LOS remained lower in some hospitals. Several independent clinical factors
      increased the pneumonia-associated length of stay with significant differences
      between hospitals. Hypoxemia and pleural effusions were the predictive variables
      of length of stay in low-risk patients and, additionally, diastolic blood
      pressure, multi-lobe involvement and hypoalbuminaemia were significant in the
      higher-risk classes III-V.

PMID- 14582919
TI  - N-terminal pro-brain natriuretic peptide in patients with acute pulmonary
      embolism.
AB  - Plasma brain natriuretic peptide (BNP), released from myocytes of ventricles upon
      stretch, has been reported to differentiate pulmonary from cardiac dyspnoea.
      Limited data have shown elevated plasma BNP levels in acute pulmonary embolism
      (APE), frequently accompanied by dyspnoea and right ventricular (RV) dysfunction.
      The aim of this study was to assess plasma N-terminal proBNP (NT-proBNP) in APE,
      and to establish whether it reflects the severity of RV overload and if it can be
      used to predict adverse clinical outcome. On admission, NT-proBNP and
      echocardiography for RV overload were performed in 79 APE patients (29 males),
      aged 63 +/- 16 yrs. Plasma NT-proBNP was elevated in 66 patients (83.5%) and was
      higher in patients with (median 4,650 pg x mL(-1) (range 61-60,958)) than without
      RV strain (363 pg x mL(-1) (16-16,329)). RV-to-left ventricular ratio and
      inferior vena cava dimension correlated with NT-proBNP. All 15 in-hospital deaths
      and 24 serious adverse events occurred in the group with elevated NT-proBNP,
      while all 13 (16.5%) patients with normal values had an uncomplicated clinical
      course. Plasma NT-proBNP predicted in-hospital mortality. Plasma N-terminal pro
      brain natriuretic peptide is elevated in the majority of cases of pulmonary
      embolism resulting in right ventricular overload. Plasma levels reflect the
      degree of right ventricular overload and may help to predict short-term outcome.
      Acute pulmonary embolism should be considered in the differential diagnosis of
      patients with dyspnoea and abnormal levels of brain natriuretic peptide.

PMID- 14582920
TI  - Sleep-disordered breathing in nonobese diabetic subjects with autonomic
      neuropathy.
AB  - To assess the occurrence and nature of sleep-disordered breathing (SDB) in 26
      adult, nonobese diabetics (18 with autonomic neuropathy (DAN+) (age 45 (41-50)
      yrs; body mass index (BMI) 24.1 (22-26) kg x m(-2)) and eight without autonomic
      neuropathy (DAN-) (age 45 (35-55) yrs; BMI 24.8 (23-26) kg x m(-2))) overnight
      full sleep studies and measurements of central and peripheral carbon dioxide
      (CO2) chemosensitivity were performed. DAN+ were divided in two subgroups,
      according to the presence (DAN+PH+; n=10) or absence (DAN+PH-; n=8) of postural
      hypotension. Ten normal subjects were studied as controls (age 42 (36-48) yrs;
      BMI 24.4 (23-25) kg x m(-2)). In contrast to DAN- and controls, who did not show
      SDB, five DAN+ (four DAN+PH- and one DAN+PH+) had an apnoea/hypopnoea index > or
      = 10 and four DAN+ (two DAN+PH- and two DAN+PH+) had an apnoea index > or = 5.
      All the events were obstructive, occurring mainly during rapid eye movement (REM)
      sleep. Ten DAN+ exhibited a mean lowest oxygen saturation < 90% during REM sleep.
      No periodic breathing or central sleep apnoeas were found in DAN+PH+, although
      they had an enhanced central chemoresponsiveness to CO2. Both DAN+ subgroups
      showed a marked reduction in peripheral CO2 chemosensitivity. In conclusion,
      adult nonobese diabetics with autonomic neuropathy, independent of the severity
      of their dysautonomy, have obstructive sleep apnoea/hypopnoea with a frequency >
      30%. A decrease in peripheral carbon dioxide chemosensitivity prevents adult
      nonobese diabetics with autonomic neuropathy and postural hypotension from
      experiencing posthyperventilatory central sleep apnoea, despite an increased
      hypercapnic central drive.

PMID- 14582921
TI  - Assessment of thoracoabdominal bands to detect respiratory effort-related
      arousal.
AB  - It would be helpful to be able to identify respiratory effort-related arousal
      (RERA) without needing to measure oesophageal pressure. Thoracoabdominal
      movements yield an indirect flow measurement from which reduction of amplitude
      and alteration of the inspiratory flow curve can be detected. The aim of this
      study was to evaluate the accuracy of using the shape and amplitude of signals
      from thoracoabdominal bands (inductance plethysmography) to detect RERAs.
      Altogether, 94 subjects suspected of having sleep apnoea but with an
      apnoea/hypopnoea index < or = 10 in full polysomnography with oesophageal
      pressure were studied. A routine polysomnographical analysis was carried out. The
      polysomnographies were then reanalysed at random to determine which of the
      identified arousals were due to RERA, as determined either by oesophageal
      pressure or by induction bands without an oesophageal pressure signal.
      Altogether, 14,617 arousals were analysed. The sensitivity and specificity to
      find RERA (arousal by arousal) from bands versus oesophageal pressure were both
      94%. The average difference of RERA index between oesophageal pressure and bands
      was -0.6. The correlation between RERA index determined by oesophageal pressure
      and bands was 0.98. To evaluate the intra and interobserver agreement, 1183
      arousals were additionally analysed. The intraobserver agreement was 91% for
      RERAs by oesophageal pressure and 80% by bands. The interobserver agreement was
      89% by oesophageal pressure and 85% by bands. The thoracoabdominal bands can be
      used to identify respiratory effort-related arousal (obstructive events not
      detected by thermistor) with similar efficacy to oesophageal pressure
      measurement. Since bands are routinely used in most polysomnographies, they can
      be used as the usual method to detect respiratory effort-related arousal, using a
      thermistor to evaluate apnoeas and hypopnoeas or as a complement to other
      methods, such as nasal cannula, which can detect apnoeas, hypopnoeas and
      respiratory effort-related arousal.

PMID- 14582922
TI  - Unsupervised self-testing of airway obstruction by forced oscillation at the
      patient's home.
AB  - As active patient cooperation is not required, the forced oscillation technique
      (FOT) could be suitable for measuring airway obstruction in routine home
      applications. Nevertheless, FOT has never been used at the patient's home to
      date. The aim of this study was to assess the feasibility of FOT and the
      reproducibility of measured respiratory resistance (Rrs) in routine patient self
      testing at home. Altogether, nine asthmatic patients self-measured their Rrs with
      a portable FOT device and spirometry for 10-14 days, in the morning and evening,
      and before and after bronchodilator inhalation. During each measurement session,
      the patients carried out four consecutive FOT measurements. Grubbs' discordancy
      test for detecting outliers was used to evaluate intermeasure reliability. Only
      4.9% of Rrs data reported by patients were rejected as artefacts. The coefficient
      of variation of Rrs was 7.9 +/- 6.3% (mean +/- SD). When compared with
      spirometry, the per cent change in Rrs for detecting a positive bronchodilator
      response showed an 83% sensitivity and 72% specificity. Unsupervised self
      measurement of respiratory resistance at the patient's home provided results
      similar to those obtained by a technician in a lung function lab. Forced
      oscillation technique could be a useful tool for the routine follow-up of
      asthmatic patients at home.

PMID- 14582923
TI  - Chronic obstructive pulmonary disease: molecular and cellular mechanisms.
AB  - Chronic obstructive pulmonary disease is a leading cause of death and disability,
      but has only recently been extensively explored from a cellular and molecular
      perspective. There is a chronic inflammation that leads to fixed narrowing of
      small airways and alveolar wall destruction (emphysema). This is characterised by
      increased numbers of alveolar macrophages, neutrophils and cytotoxic T
      lymphocytes, and the release of multiple inflammatory mediators (lipids,
      chemokines, cytokines, growth factors). A high level of oxidative stress may
      amplify this inflammation. There is also increased elastolysis and evidence for
      involvement of several elastolytic enzymes, including serine proteases,
      cathepsins and matrix metalloproteinases. The inflammation and proteolysis in
      chronic obstructive pulmonary disease is an amplification of the normal
      inflammatory response to cigarette smoke. This inflammation, in marked contrast
      to asthma, appears to be resistant to corticosteroids, prompting a search for
      novel anti-inflammatory therapies that may prevent the relentless progression of
      the disease.

PMID- 14582924
TI  - Health and socioeconomic impact of work-related asthma.
AB  - There is accumulating evidence that the workplace environment contributes
      significantly to the general burden of asthma. The purpose of this review is to
      explore the respiratory health and socioeconomic consequences of work-related
      asthma by addressing a series of controversial issues: 1) what is the natural
      history of occupational asthma and in what ways does ongoing exposure to the
      causal agent impact clinical outcomes?; 2) how does the natural history of
      irritant-induced asthma differ in its health outcomes from immunologically
      mediated occupational asthma?; 3) do working conditions have a significant impact
      on asthma regardless of the aetiology of the disease?; 4) what is the scope of
      work disability from work-related-asthma in social and economic terms?; 5) what
      is the clinician's role in reducing the respiratory health consequences of work
      related asthma? 6) to what extent do existing compensation and other social
      insurance schemes successfully address occupational asthma and work-aggravated
      asthma?

PMID- 14582925
TI  - Flexible endoscopy of paediatric airways.
AB  - Paediatric fibreoptic bronchoscopy is used for ever wider indications, and
      increasingly used in many contexts, including paediatric and neonatal intensive
      care. The report of this Task Force contains an overview on the current
      applications of paediatric bronchoscopy. The report discusses the facilities and
      equipment needed for the procedure, including the newly developed bronchoscopes
      which are allowing intervention even in very small children. The indications of
      both flexible and rigid bronchoscopes in the context of newer and smaller
      flexible endoscopic equipment are also considered. The care of the instruments,
      including disinfection and sterilisation, is fully documented. Patient management
      is described, including the relative merits of conscious sedation and general
      anaesthesia, as well as special settings for the procedure, including the needs
      in intensive care. Special procedures, increasingly performed bronchoscopically
      are described. These include bronchoalveolar lavage, endobronchial and
      transbronchial biopsy, laser therapy, bronchography, and endoscopic intubation
      and drug therapy. Finally, neonatal bronchoscopy is discussed, and the ethics of
      bronchoscopic procedures, including bronchoscopic research in children. Advances
      in instrumentation, and also improved anaesthetic techniques, allow fibreoptic
      bronchoscopy to be safely performed in even very small, sick infants, provided
      proper precautions are taken.

PMID- 14582926
TI  - Fatal primary pulmonary hypertension in a 30-yr-old female with APECED syndrome.
AB  - Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is caused
      by mutations in the autoimmune regulator (AIRE) gene, which has a central
      function in maintaining immunological tolerance. A number of conditions with
      proven or likely autoimmune pathogenesis occur in APECED: hypoparathyroidism,
      adrenocortical insufficency, candidiasis, hypogonadism, type 1 diabetes,
      hypothyroidism, hypophysitis, hepatitis, malabsorption, nail dystrophy, enamel
      hypoplasia and keratopathy. It is not clear which factors are responsible for
      variation in clinical picture of APECED, but human leukocyte antigen (HLA)
      genotype may be important. The authors report the first description of a case of
      primary pulmonary hypertension (PPH) in patient with APECED, caused by R257X
      mutation in AIRE. The HLA genotype of the patient (DRB1*01/DRB1*11,
      DQB1*0301/DQB1*0501) has been previously reported as a predisposing factor to
      PPH. The findings from this study, provided that other similar cases are
      reported, suggest that immune deregulation plays a role in the pathogenesis of
      primary pulmonary hypertension.

PMID- 14582927
TI  - A 26-yr-old female with persistent cough. Intrathoracic extramedullary
      haematopoiesis in a patient with beta-thalassemia intermedia.

PMID- 14582928
TI  - Sex differences in respiratory symptoms.

PMID- 14582929
TI  - Conceptual, methodological, and statistical issues in developmental
      psychopathology: a special issue in honor of Paul E. Meehl.

PMID- 14582930
TI  - Taxometrics and developmental psychopathology.
AB  - Developmental psychopathologists have criticized categorical classification
      systems for their inability to account for within-group heterogeneity in
      biological, etiological. developmental, and cultural influences on behavior.
      Dichotomizing continuous scores of symptom severity is also inadvisable
      statistically. Perhaps because of a resulting wariness of categorizing, few
      explorations into the ontological status of traits or disorders as dimensional
      versus discrete have been conducted. It is argued here that the limitations of
      categorizing have little to do with the ontological status of traits and that
      developmental psychopathologists should be concerned with identifying discrete
      behavioral syndromes. Common taxometric methods for resolving discrete traits are
      described, and questions of concern to developmental psychopathologists are
      outlined that can be addressed through taxometrics studies. These include (a)
      identifying children who are at risk for future psychopathology, (b) identifying
      discrete subtypes within current diagnostic classes, (c) locating sensitive
      periods in the development of discrete pathological traits, (d) discovering
      moderators of treatment outcome, and (e) elucidating mechanisms of equifinality
      and multifinality. Although most behavioral traits probably are distributed
      continuously, identifying those that are discrete will advance the science of
      developmental psychopathology. Disorders for which taxometric analyses might be
      applied include anxiety, attention deficit hyperactivity disorder, autism
      spectrum disorders, conduct problems, depression, and schizophrenia.

PMID- 14582931
TI  - Natural categories or fundamental dimensions: on carving nature at the joints and
      the rearticulation of psychopathology.
AB  - The question of whether to view psychopathology as categorical or dimensional
      continues to provoke debate. We review the many facets of this argument. These
      include the pragmatics of measurement; the needs of clinical practice; our
      ability to distinguish categories from dimensions empirically; methods of
      analysis appropriate to each and how they relate; and the potential theoretical
      biases associated with each approach. We conclude that much of the debate is
      misconceived in that we do not observe pathology directly; rather, we observe its
      properties. The same pathology can have some properties that are most easily
      understood using a dimensional conceptualization while at the same time having
      other properties that are best understood categorically. We suggest replacing
      Meehl's analogy involving qualitatively distinct species with an alternative
      analogy with the "duality" of light, a phenomenon with both wave- and particle
      like properties.

PMID- 14582932
TI  - Research strategies in developmental psychopathology: dimensional identity and
      the person-oriented approach.
AB  - This article deals with alternative research strategies for developmental
      psychopathology. It argues that most applications of statistical methods in
      empirical research are variable centered, not person oriented. As a result,
      conclusions are often drawn that fail to do justice to the diverse nature of
      populations. It is recommended that we take seriously the importance of the
      implications of data aggregation. The difficulties of making inferences from a
      more aggregated level of analysis to a less aggregated level are explained and
      exemplified. We explain that a set of variables displays dimensional identity if
      the variable relationships remain unchanged across the levels or categories of
      other variables. Data examples of intelligence divergence and of Child Behavior
      Checklist subpopulation differences show that lack of dimensional identity can
      lead to incorrect conclusions. Schmitz' theorems on aggregation and the validity
      of results at the aggregate level for individuals are illustrated using data from
      a study on the development of alcoholism and discussed from a person-oriented
      perspective. Statistical methods suitable for person-oriented data analysis are
      reviewed.

PMID- 14582933
TI  - Implications of latent trajectory models for the study of developmental
      psychopathology.
AB  - The field of developmental psychopathology is faced with a dual challenge. On the
      one hand, we must build interdisciplinary theoretical models that adequately
      reflect the complexity of normal and abnormal human development over time. On the
      other hand, to remain a viable empirical science, we must rigorously evaluate
      these theories using statistical methods that fully capture this complexity. The
      degree to which our statistical models fail to correspond to our theoretical
      models undermines our ability to validly test developmental theory. The broad
      class of random coefficient trajectory (or growth curve) models allow us to test
      our theories in ways not previously possible. Despite these advantages, there
      remain certain limits with regard to the types of questions these models can
      currently evaluate. We explore these issues through the pursuit of three goals.
      First, we provide an overview of a variety of trajectory models that can be used
      for rigorously testing many hypotheses in developmental psychopathology. Second,
      we highlight what types of research questions are well tested using these methods
      and what types of questions currently are not. Third, we describe areas for
      future statistical development and encourage the ongoing interchange between
      developmental theory and quantitative methodology.

PMID- 14582934
TI  - Research strategies for capturing transactional models of development: the limits
      of the possible.
AB  - Transactional models have informed research design and interpretation in studies
      relevant to developmental psychopathology. Bidirectional effects between
      individuals and social contexts have been found in many behavioral and cognitive
      domains. This review will highlight representative studies where the
      transactional model has been explicitly or implicitly tested. These studies
      include experimental, quasiexperimental, and naturalistic designs. Extensions of
      the transactional model have been made to interventions designed to target
      different aspects of a bidirectional system in efforts to improve developmental
      outcomes. Problems remain in the need to theoretically specify structural models
      and to combine analyses of transactions in the parent-child relationship with
      transactions in the broader social contexts. Longitudinal studies with sufficient
      time points to assess reciprocal processes continue to be important. Such
      longitudinal investigations will permit identifying developmental periods where
      the child or the context may be most influential or most open to change.

PMID- 14582935
TI  - Dynamic systems methods for models of developmental psychopathology.
AB  - A survey of dynamic systems (DS) methods appropriate for testing systems-based
      models in developmental psychopathology is provided. The rationale for developing
      new methods for the field is reviewed first. In line with other scholars, we
      highlight the fundamental incompatibility between developmentalists' organismic,
      open systems models and the mechanistic research methods with which these models
      are tested. Key DS principles are explained and their commensurability with
      developmental psychopathologists' core theoretical concerns are discussed. Next,
      a survey of research designs and methodological techniques currently being used
      and refined by developmental DS researchers is provided. The strengths and
      limitations of each approach are discussed throughout this review. Finally, we
      elaborate on one specific dynamic systems method, state space grids, which
      addresses many of the limitations of previous DS techniques and may prove most
      useful for the discipline. This approach was developed as a middle road between
      DS methods that are mathematically heavy on the one hand and purely descriptive
      on the other. Examples of developmental and clinical studies that have applied
      state space grids are reviewed and suggestions for future analyses are made. We
      conclude with some implications for the application of this new methodology for
      studying change processes in clinical research.

PMID- 14582936
TI  - Early experiences and psychological development: conceptual questions, empirical
      illustrations, and implications for intervention.
AB  - This paper reviews alternative conceptual and descriptive models of how early
      exposure to risk may predict later development. Particular attention is paid to
      the methodological and data analytic strategies for differentiating among the
      models. Example empirical illustrations of human studies are then provided that
      highlight the potential significance of early experiences for
      behavioral/emotional development. Finally, implications of these models of early
      experiences for intervention and prevention are examined and identified as an
      important methodological tool for further research.

PMID- 14582937
TI  - Toward the next quarter-century: conceptual and methodological challenges for
      attachment theory.
AB  - Attachment theory and research have offered fundamental insights into early
      sociopersonality development for the past quarter-century. As its scope expands
      throughout the life course with applications to developmental psychopathology,
      however, attachment work faces important conceptual and methodological
      challenges. These include (a) expanding Bowlby's theoretical formulations to
      address developmental changes in the nature of attachment organization beyond
      infancy, the converging influence of multiple attachment relationships, and the
      nature and development of internal working models: (b) systematically validating
      assessments of attachment security for older ages in the context of enhanced
      theoretical understanding of how attachment itself changes with age; (c) new
      methodological approaches to understanding the relations between attachment and
      later behavior in light of empirical evidence of stability and change in
      attachment security and the need for explicit theoretical predictions of the
      sequelae of attachment security; and (d) more complex conceptualizations of the
      associations among attachment, contextual risk, and later behavior. These are
      similar to the challenges facing the original pioneers of attachment theory and
      research, suggesting that familiar problems must now be reconsidered against the
      landscape of new applications of attachment work and the insights of contemporary
      developmental science.

PMID- 14582938
TI  - The development of psychopathology in females and males: current progress and
      future challenges.
AB  - In recent years, the role of gender in the development of psychopathology has
      increasingly attracted the attention of researchers, theoreticians, and other
      professionals interested in the well-being of children and adolescents. This
      interest has taken diverse forms, ranging from the examination of sex differences
      in the prevalence of adjustment difficulties to the exploration of unique
      etiologies and trajectories in the development of psychopathology for boys versus
      girls. In this paper we (a) critically examine the current status of available
      theories, research, and methods related to the study of gender and
      psychopathology and provide recommendations for future work; (b) identify
      promising new trends that appear to have utility for enhancing our understanding
      of the role of gender in the development of adjustment difficulties; and (c)
      generate conclusions regarding gender and psychopathology by integrating
      information from past and present work with new ideas about fruitful directions
      for future inquiry.

PMID- 14582939
TI  - Psychosocial development in racially and ethnically diverse youth: conceptual and
      methodological challenges in the 21st century.
AB  - As the US population becomes more diverse in the 21st century, researchers face
      many conceptual and methodological challenges in working with diverse
      populations. We discuss these issues for racially and ethnically diverse youth,
      using Spencer's phenomenological variant of ecological systems theory (PVEST) as
      a guiding framework. We present a brief historical background and discuss
      recurring conceptual flaws in research on diverse youth, presenting PVEST as a
      corrective to these flaws. We highlight the interaction of race, culture,
      socioeconomic status, and various contexts of development with identity formation
      and other salient developmental processes. Challenges in research design and
      interpretation of data are also covered with regard to both assessment of
      contexts and developmental processes. We draw upon examples from neighborhood
      assessments, ethnic identity development, and attachment research to illustrate
      conceptual and methodological challenges, and we discuss strategies to address
      these challenges. The policy implications of our analysis are also considered.

PMID- 14582940
TI  - Moving research on resilience into the 21st century: theoretical and
      methodological considerations in examining the biological contributors to
      resilience.
AB  - Empirical investigations of resilience over the past 30 years have examined a
      wide range of psychosocial correlates of, and contributors to, this phenomenon.
      Thus far, theoretical treatments of resilience have focused almost exclusively on
      psychosocial levels of analysis to derive explanatory models. However, there have
      been no formal discussions of either theory or research that have examined the
      biological contributors to, or correlates of, competent functioning despite the
      experience of adversity. This paper seeks to fill this gap and sets forth a
      preliminary theoretical framework and outline of empirical strategies for
      studying the biological underpinnings of resilience. The initial sections of the
      paper discuss the particular suitability of a transactional organizational
      theoretical perspective as a conceptual foundation for including a biological
      level of analysis within the extant theoretical framework of resilience.
      Subsequently, other important theoretical considerations for the inclusion of a
      biological perspective on resilience are discussed, including the avoidance of an
      approach that would reduce resilience to merely a biological process, the
      application of the constructs of multifinality and equifinality to a biological
      perspective on resilience, as well as a general discussion of the potential for
      utilization of brain imaging and other technologies in the study of resilience.
      The possible relation between the mechanisms of neural plasticity and resilience
      are examined in some detail, with specific suggestions concerning research
      questions needed to examine this association. Sections of the paper discuss the
      likely relation of several areas of brain and biological functioning with
      resilience, including emotion, cognition, neuroendocrine and immune functioning,
      and genetics. The paper concludes with a discussion of the implications of a
      biological perspective on resilience for preventive interventions.

PMID- 14582942
TI  - Nursing and practice development.

PMID- 14582941
TI  - Conceptual, methodological, and statistical challenges in brain imaging studies
      of developmentally based psychopathologies.
AB  - Brain imaging studies in developmentally based psychopathologies most often use
      magnetic resonance imaging (MRI) to study regional volumes, task-related
      activity, neurometabolite concentrations, or the paths of fiber tracts within the
      brain. Methodological challenges for the use of MRI in studying these disorders
      include understanding the ultrastructural correlates of brain structure and
      function that are below the limits of resolution of this imaging modality and
      developing better methods for approximating the anatomical boundaries of the
      cytoarchitectonic units that are defined by those ultrastructural
      characteristics. Conceptual challenges include distinguishing findings that
      represent pathophysiologically central causes from compensatory and epiphenomenal
      effects, a difficulty that stems directly from the inherently correlational
      nature of imaging data. The promise of functional imaging studies must capitalize
      on the specificity of the cognitive and behavioral probes that are used to
      illuminate core features of the pathophysiology of developmental disorders, while
      recognizing the assumptions and limitations of the subtraction paradigms that are
      used to isolate the brain functions of interest. Statistical challenges include
      incorporating adequate statistical models for scaling effects within the brain,
      as well as modeling important demographic correlates that contribute to the
      substantial interindividual variability inherent in most imaging data.
      Statistical analyses need to consider the substantial intercorrelation of
      measures across the brain and the importance of correcting for multiple
      statistical comparisons, as well as the need for improved methods for brain
      warping and for assessing effective connectivity in functional imaging studies.

PMID- 14582943
TI  - The factors influencing clinical leadership.

PMID- 14582944
TI  - Clinical practice development in Central Coast Health.
AB  - Engagement in clinical practice development may be achieved in a range of ways.
      In this paper we describe the formation of a strategic plan for clinical practice
      development for Central Coast Health. The plan specifically builds on the work
      that has already been achieved by clinicians and is inclusive of the multi
      disciplinary team. In order to clarify the strategic direction, three levels of
      clinical practice development are offered as examples of increasingly intensive
      clinical practice development. In the strategic plan senior personnel are
      recruited to support area-wide developments. At the same time clinicians are
      supported to work on specific local projects creating a simultaneous top-down and
      bottom-up approach. Preparation of clinicians for the challenges of team building
      and change in practice ensures that people choosing to engage in clinical
      practice have realistic expectations of the commitment and rewards that may be
      expected.

PMID- 14582945
TI  - The meaning of practice development: evidence from the field.
AB  - This paper sets out to explore the meaning of practice development. The data from
      which this exploration is derived is largely drawn from an empirical research
      project that set out to explore practice development through concept analysis.
      The paper argues for a model of practice development that is focused on achieving
      increased effectiveness in patient-centred care. It argues that one-off changes
      in practice are not the same as a sustained systematic development of practice
      that focuses on achieving cultural changes in practice settings, ie the context
      of practice. It will be argued that facilitation is a key concept underpinning
      practice development work, but that in itself, facilitation is a misunderstood
      and abused concept. Finally, the consequences of practice development activity
      will be outlined and the need for further research in this area highlighted.

PMID- 14582947
TI  - Nursing and the health system: at the peaks. Interview by Jennifer Rowe.

PMID- 14582946
TI  - Practice development in a postmodern world: thinking globally, acting locally.

PMID- 14582948
TI  - Putting the action into learning: the experience of an action learning set.
AB  - As part of a practice development initiative the nursing staff of a special care
      nursery unit chose to begin an action learning set. The set was established to
      enable nursing staff to participate in a learning activity which focused on
      personal as well as team development. This was facilitated by a practice
      development nurse (researcher) who although not part of the nursing team, worked
      within the unit on a supernumerary basis throughout the study period. The set
      members identified and explored issues from clinical practice through a process
      of questioning, reflection, and challenging one another with an aim to improving
      the care delivered to patients and their families. This paper describes the
      process involved in establishing the set and the journey the set has taken since
      its inception in May 2002. The main areas covered in this paper include an
      overview of the practice development initiative, a brief outline of action
      learning including the processes involved, how the set was established, what it
      is like to be a set member, the development of skills and knowledge, the personal
      growth that has resulted from participation, and how the set is being evaluated.

PMID- 14582949
TI  - Developing facilitation skills--a narrative.
AB  - Effective facilitation has been identified in the literature as one of three
      elements, along with context and evidence, that have a dynamic and coexisting
      relationship to enable the successful uptake of evidence into practice. This
      paper presents an overview of the concept of facilitation within the context of
      practice development, ahead of a personal and professional reflective account of
      a 'developing facilitator'. In the summer of 2001, the author was instrumental in
      organising the first Practice Development School in Melbourne. Thrown in at the
      deep end, she found herself co-facilitating with an experienced practice
      developer from the United Kingdom. Having never facilitated in the arena of an
      action learning group, nor worked in the field of practice development, there was
      initially a sense of impending overload and drowning in the new knowledge and
      skills that needed to be acquired. Drawing upon the work of narrative inquiry the
      author shares her experiences in the anticipation that in telling her story it
      will assist others in their journey of becoming a facilitator.

PMID- 14582950
TI  - The nursing shortage: part way down the slippery slope.
AB  - The shortage of nurses has reached a crisis point for health care services. A
      number of issues including the effects of economic rationalism, generational
      differences, working conditions and nurse education are revisited in a discussion
      that aims to refuel the debate on workplace reform for nurses. Economic
      rationalism has altered the healthcare service landscape. Attempts to balance
      service delivery with workforce resources have led to possibly unforeseen
      changes. Highly skilled nurses are required in acute services, however resource
      allocation may prevent this. The nursing workforce is aging although the current
      nursing workforce consists of three generations: baby boomers, generation X and
      generation Y. There are significant ideological and work organisational
      differences between these generations leading to possible conflict between
      nurses. The pool of available nurses to fill employment vacancies is finite.
      Attracting overseas nurses to fill nurse vacancies will leave vacancies elsewhere
      and is not a long-term solution to the nursing shortage. Moreover, if the
      workplace has not addressed the reasons why nurses have left the health care
      workplace then there is a real danger of losing those recently attracted back
      into the workplace. Working conditions are a critical element within the
      retention puzzle. Job satisfaction dimensions such as autonomy and professional
      relationships are key components for improving working conditions. The final
      issue explored is the question of whether the tertiary education system is the
      most appropriate place in which to develop and educate nurses. It is suggested
      that workplace reforms should be the target of retention strategies rather than
      changes in the educational process of nursing.

PMID- 14582951
TI  - CPD: Searching the literature: advanced techniques for exhaustive searching.

PMID- 14582952
TI  - Analysis of fenhexamid in caneberry, blueberry, and pomegranate by liquid
      chromatography-tandem mass spectrometry.
AB  - An analytical method for the determination of fenhexamid [N-(2,3-dichloro-4
      hydroxyphenyl)-1-methylcyclohexanecarboxamide] in caneberry, blueberry, and
      pomegranate was developed utilizing acetone extraction, column cleanup, liquid
      liquid partitioning, and liquid chromatography-tandem mass spectroscopy (LC
      MS/MS) for detection. Method validation recoveries ranged from 91 to 96% for
      caneberry, from 80 to 91% for blueberry, and from 74 to 95% for pomegranate.
      Control samples collected from IR-4 trials for all matrixes had residue levels of
      <0.020 ppm. Fenhexamid-treated field samples had residue levels that ranged from
      0.46 to 16.11 ppm (caneberry), from 0.87 to 2.91 ppm (blueberry), and from 1.59
      to 1.85 ppm (pomegranate). The method was validated to a limit of quantitation of
      0.020 ppm, and the limit of detection was 0.009 ppm.

PMID- 14582953
TI  - An assay to estimate tannins added to postmortem Turkey meat.
AB  - A method for quantification of tannins in wine was adapted to determine tannins
      added to turkey meat. Standard curves containing varying amounts of GSE [0, 0.5,
      1.0, 1.5, 2.0, 2.5, and 5.0%, (w/w)] as a source of tannins were developed. The
      R(2) value of the mean standard curve was 0.9992. The overall percent recovery of
      GSE in meat was determined to be 54.78%. Results showed that estimation of GSE in
      four out of five of the spiked samples was less than or equal to 10%. It is
      unclear as to why spiked samples at 0.048 mg of GSE were always underestimated
      (25.0%). Overall, the method seems applicable for estimation of tannins in
      poultry meat and is probably applicable to estimation of tannins in other meat
      products.

PMID- 14582954
TI  - Comparison of methods for the quantitative determination of phospholipids in
      lecithins and flour improvers.
AB  - Phospholipid classes were determined qualitatively and quantitatively in eight
      commercial lecithins and three flour improvers by thin-layer chromatography
      (TLC), high-performance liquid chromatography (HPLC), and (31)P nuclear magnetic
      resonance spectroscopy ((31)P NMR). The total amounts of phospholipids as well as
      the amounts of phospholipid classes in the samples were comparable but depended
      on the method used for quantification. Highest selectivity was provided by (31)P
      NMR as all phospholipids and lysophospholipids could easily be quantified. By TLC
      only lysophosphatidylcholine could not be quantified, whereas HPLC was the method
      with the lowest selectivity, because lysophospholipids, except
      lysophosphatidylethanolamine, could not be determined. Sensitivity was best for
      HPLC and TLC with detection limits of 20-170 mug/mL. By means of (31)P NMR these
      figures increased by a factor of 10-70. The coefficients of variation were 5.5,
      6.8, and 12.8% for quantification by TLC, HPLC, and (31)P NMR, respectively,
      showing that TLC was the method with the best reproducibility. Altogether, (31)P
      NMR can be recommended for the quantification of phospholipids, because it is
      easy to perform and results can be obtained quickly. As it requires minimum
      instrumental equipment, TLC is a good alternative to (31)P NMR. If high
      sensitivity is required, HPLC is the best method.

PMID- 14582955
TI  - Use of DSC to detect the heterogeneity of hydrothermal stability in the
      polyphenol-treated collagen matrix.
AB  - The hydrothermal stability of the collagen matrixes treated with plant
      polyphenols (tannins) depends on not only the strength of the polyphenol-collagen
      interactions but also the distribution uniformity of polyphenolic molecules
      within the collagen fibrils. Traditional methods of uniformity tests rely heavily
      on the expertise of workers and are thus subjective. This paper describes a
      differential scanning calorimetry (DSC) study of the sheepskin collagen samples
      treated with hydrolyzable tannins, including two commercial tannins' extracts
      (chestnut and valonea), two pure ellagitannins (vescalagin and castalagin), and
      six synthetic gallotannins (di-galloyl-ethylene glycol (DGE), tri-galloyl
      glycerol, tetra-galloyl-meso-erythritol, penta-galloyl-adonitol, penta-galloyl
      glucose, and hexa-galloyl-ducitol). The collagen sample without polyphenol
      treatment and the sample treated with DGE showed a single sharp peak in their DSC
      thermogram with a full peak width at half height (fwhh) of 3-4 degrees C. The
      samples treated with other tannins all showed multiple peak DSC profiles with the
      fwhh of each peak at about 3-4 degrees C. These multiple peak profiles imply that
      in these polyphenol-treated samples, there is a distribution of collagen
      molecules having different hydrothermal stability. The results have demonstrated
      that DSC offers an objective method to detect the stability heterogeneity of
      collagen matrixes in the solid state, providing a useful tool for the leather
      industry to evaluate the uniformity of leather tanning.

PMID- 14582956
TI  - Screening methods to measure antioxidant activity of sorghum (sorghum bicolor)
      and sorghum products.
AB  - Specialty sorghums, their brans, and baked and extruded products were analyzed
      for antioxidant activity using three methods: oxygen radical absorbance capacity
      (ORAC), 2,2'-azinobis (3-ethyl-benzothiazoline-6-sulfonic acid) (ABTS), and 2,2
      diphenyl-1-picrylhydrazyl (DPPH). All sorghum samples were also analyzed for
      phenolic contents. Both ABTS and DPPH correlated highly with ORAC (R(2) = 0.99
      and 0.97, respectively, n = 18). Phenol contents of the sorghums correlated
      highly with their antioxidant activity measured by the three methods (R(2) >or=
      0.96). The ABTS and DPPH methods, which are more cost effective and simpler, were
      demonstrated to have similar predictive power as ORAC on sorghum antioxidant
      activity. There is a need to standardize these methods to allow for data
      comparisons across laboratories.

PMID- 14582957
TI  - Evaluation of a commercial enzyme-based serum cholesterol test kit for analysis
      of phytosterol and phytostanol products.
AB  - Plant sterols (phytosterols) have been shown to possess serum cholesterol
      lowering properties. In recent years, several phytosterol-enriched functional
      food products have been developed and marketed. Some phytosterol products contain
      common unsaturated sterols and some contain a subset of phytosterols called
      phytostanols (saturated sterols, also called plant stanols). Current methods for
      the quantitative analysis of plant sterols are labor intensive and require
      sophisticated gas or liquid chromatographs. In this study, a popular commercial
      spectrophotometric serum cholesterol test kit was evaluated for the analysis of
      plant sterols. The results indicate that the method could be modified to analyze
      phytosterols and phytostanols by increasing the incubation time. Both free
      phytosterols and fatty acyl phytosteryl esters were quantitatively analyzed, but
      ferulate phytosteryl esters, such as those that are found in corn and other
      cereals, were not hydrolyzed by the enzymes in the test kit and therefore were
      not detected.

PMID- 14582958
TI  - Development of antibodies for the detection of N-acetyl-glufosinate.
AB  - Glufosinate is a widely used herbicide, which is difficult to detect by
      conventional analytical techniques. For many other herbicides, suitable
      antibodies have been raised for immunoassay development. Unfortunately,
      glufosinate is a very small molecule and difficult to immunize with. Thus, a
      derivatization-assisted immunoassay (DAIA) using the target analyte N-acetyl
      glufosinate (NAG) was constructed. The activated hapten was synthesized by a new
      approach, using a homobifunctional cross-linker suberic acid bis(N
      hydroxysuccinimide ester). The preparation of a suitable conjugate, the
      immunization, and the characterization of polyclonal antibodies are shown. The
      determination of the conjugation density (hapten density) of the immunogens was
      performed by four different methods (high-performance liquid chromatography with
      a refractive index detector, total reflection X-ray fluorescence, inductively
      coupled plasma mass spectrometry, and matrix-assisted laser desorption/ionization
      time-of-flight mass spectrometry), which gave similar results. The limit of
      detection was 17 mug/L NAG in water for the direct competitive enzyme
      immunoassay. NAG is also a main metabolite of glufosinate in resistant transgenic
      plants. The antibodies might be useful for the selective detection of NAG in the
      presence of the parent compound glufosinate (cross-reactivity 0.13%) and other
      metabolites.

PMID- 14582959
TI  - LC-MS/MS analysis of lysophospholipids associated with soy protein isolate.
AB  - Approximately 20-25% of babies consuming formula are fed formulas containing soy
      protein as the sole protein source. Isoflavone phytoestrogens are considered as
      major bioactive components present in soy protein isolate (SPI) and the most
      widely studied phytochemicals in human diets and soy infant formulas. In the
      present study, LC-MS/MS analysis of SPI phytochemical extract resulted in
      identifications of fifty-six lysophospholipids (lyso-PL), including eighteen
      lysophosphatidylcholines (lyso-PC), twelve lysophosphatidylethanolamines (lyso
      PE), eleven lysophosphatidylinositols (lyso-PI), eleven lysophosphatidic acids
      (lyso-PA) and four lysophosphatidylglycerols (lyso-PG). The LC-MS/MS conditions
      were first developed using commercially available standard mixtures. Under these
      conditions, lyso-PL compounds could be separated by LC and yielded unique
      fragments and neutral losses in the electrospray ionization mass spectrometry
      (ESI-MS) with both positive- and negative-ion modes, quite indicative of the
      polar headgroups for different subclasses. This is the first characterization of
      lyso-PL in SPI. Lyso-PLs are important cell signaling and growth factor molecules
      experimentally linked to cardiovascular function and disease, cancer, and
      neurological disorders. These findings suggest that biological effects of PLs
      associated with SPI in infants clearly needs to be considered as part of an
      overall evaluation of potential health benefits.

PMID- 14582960
TI  - Sterol ferulates, sterols, and 5-alk(en)ylresorcinols from wheat, rye, and corn
      bran oils and their inhibitory effects on Epstein-Barr virus activation.
AB  - Sterol ferulate, free sterol, and 5-alk(en)ylresorcinol constituents of wheat,
      rye, and corn bran oils were studied. Among the sterol ferulates, one novel
      compound, 24-methylenecholestanol ferulate (7), along with six known compounds,
      namely, 24-methylcholestanol ferulate (1), 24-methylcholesterol ferulate (2), 2
      methyllathosterol ferulate (3), stigmastanol ferulate (4), sitosterol ferulate
      (5), and schottenol ferulate (6), were isolated and characterized. Five known
      free sterols, namely, 24-methylcholesterol (8), stigmastanol (9), sitosterol
      (10), schottenol (11), and stigmasterol (12), were isolated and identified. 5
      Alk(en)ylresorcinols were found in wheat and rye bran oils but not in corn bran
      oil. Of these, one new compound, 5-n-(2'-oxo-14'-Z-heneicosenyl) resorcinol (19),
      and seven known compounds, namely, 5-n-heptadecyl- (13), 5-n-nonadecyl- (14), 5-n
      heneicosyl- (15), 5-n-tricosyl- (16), 5-n-pentacosyl- (17), 5-n-(14'-Z
      nonadecenyl)- (18), and 5-n-(2'-oxoheneicosyl)resorcinols (20), were isolated and
      characterized. These compounds were evaluated with respect to their inhibitory
      effects on the induction of Epstein-Barr virus early antigen (EBV-EA) by 12-O
      tetradecanoylphorbol-13-acetate (TPA) in Raji cells, which is known to be a
      primary screening test for antitumor promoters. Four compounds, 1, 2, 4, and 11,
      showed potent inhibitory effects on EBV-EA induction.

PMID- 14582961
TI  - Chemical composition and antioxidant activity of phenolic compounds from wild and
      cultivated Sclerocarya birrea(Anacardiaceae) leaves.
AB  - A quantitative study of the phenolic constituents of wild and cultivated leaves
      of Sclerocarya birrea(Anacardiaceae) was carried out by HPLC-UV/PDA and LC-MS.
      Phytochemical analysis of the methanol extract of wild plants led to the
      isolation of one new flavonol glycoside, quercetin 3-O-alpha-l-(5' '-galloyl)
      arabinofuranoside (1), and eight known phenolic compounds; two epicatechin
      derivatives were also isolated from the same extract of the cultivated species.
      The antioxidant activity of all isolated compounds was determined by measuring
      free radical scavenging effects using the Trolox equivalent antioxidant capacity
      assay and the coupled oxidation of beta-carotene and linoleic acid (autoxidation
      assay).

PMID- 14582962
TI  - Antioxidant activity of organic extracts from aqueous infusions of sage.
AB  - The antioxidant activity of aqueous infusions of sage emerges from specific
      components present in that herb. In an attempt to investigate the chemical nature
      and properties of these components, four organic solvent extracts from aqueous
      infusions of sage were examined. HPLC analyses of these extracts led to the
      separation of a number of components, of which four were identified and
      quantified through the use of standard compounds of known chromatographic HPLC
      profiles. These compounds are the diterpenes carnosic acid, carnosol, and
      rosmanol and the hydroxycinnamic acid caffeic acid. The antioxidant activity and
      polyphenol content were determined in the four organic solvent extracts and the
      left-over aqueous fraction. Both polyphenolic and nonpolyphenolic substances
      present in the extracts arise as significant contributors to the observed
      antioxidant activity of the derived extracts and thus sage itself. In this sense,
      they reflect the antioxidant potential of the aqueous infusions of sage toward
      reactive oxygen species generated through variable mechanisms of iron-promoted
      oxidative processes.

PMID- 14582963
TI  - Long chain alkanes in silk extracts of maize genotypes with varying resistance to
      Fusarium graminearum.
AB  - The alkane content of the silks of nine maize genotypes was analyzed to
      investigate the role of silk wax in resistance to Fusarium graminearum. Silk
      samples were collected 2, 4, 6, and 8 days after silk emergence and divided into
      three sections: exposed silk, silk channel silk, and silk that is under the husk
      and overlying the kernels. Four major unbranched alkanes (C(25), C(27), C(29),
      and C(31)) and three isoalkanes (C(27i), C(29i), and C(31i)) were identified.
      Total alkane contents were highest in the exposed silk followed by the silk
      channel silk, with the lowest in the youngest silk closest to the kernels. In the
      silk channel and overlying kernel silks, the moderately resistant inbred CO272
      consistently had the highest alkane content. None of the other inbreds with
      improved resistance had as high a level of alkanes as CO272, indicating that
      alkane content is not a major mechanism of resistance.

PMID- 14582964
TI  - Phylogeny of Astragalus in China: molecular evidence from the DNA sequences of 5S
      rRNA spacer, ITS, and 18S rRNA.
AB  - Radix Astragali (root of Astragalus; Huangqi) is a traditional Chinese medicine
      commonly used as an immunostimulant, hepatoprotective, diuretic, antidiabetic,
      analgesic, expectorant, and sedative drug. Although the species of Radix
      Astragali have been defined as Astragalus membranaceus and A. membranaceus var.
      mongholicus in Pharmacopoeia of China, their taxonomy remains controversial. The
      phylogenetic relationships among 10 Astragalus taxa, which are commonly found in
      China including A. membranaceus, A. membranaceus var. mongholicus, Astragalus
      propinquus, Astragalus lepsensis, Astragalus aksuensis, Astragalus hoantchy,
      Astragalus hoantchy subsp. dshimensis,Astragalus lehmannianus, Astragalus
      sieversianus, and Astragalus austrosibiricus, were determined using the DNA
      sequences of the 5S ribosomal RNA (5S rRNA) spacer, internal transcribed spacer
      region (ITS), and 18S rRNA coding region. The 5S rRNA spacer, ITS, and 18S rRNA,
      amplified by polymerase chain reaction from the isolated genomic DNAs, were
      sequenced. By using neighbor-joining and maximum parsimony analyses, phylogenetic
      trees were mapped by their sequence diversity. A. membranaceus and A.
      membranaceus var. mongholicus shared the greatest sequence homology. In addition,
      A. propinquus shared a closer relationship with A. membranaceus and A.
      membranaceus var. mongholicus, while other Astragalus species were less closely
      related. This is the first paper to show the phylogenetic relationship of
      Astragalus species related to Radix Astragali in China by the molecular genetic
      approach.

PMID- 14582965
TI  - Tests for the depolymerization of polyacrylamides as a potential source of
      acrylamide in heated foods.
AB  - This study was conducted to test the possibility that polyacrylamides used in
      agriculture may contribute to acrylamide formation in heated foods by thermal
      depolymerization. Two samples of polyacrylamide with low molecular weights of 1.5
      and 10 kDa were used to test for in-chain and end-chain depolymerization. They
      were added as aqueous solutions to filter paper for heating in a drying/dry
      environment and added to a cooking oil for heating in a fatty environment. The
      heating conditions were 175 degrees C for 15 and 30 min, respectively. Both
      regimens were tested in the absence and presence of the redox-active metal ions
      Fe(III) and Cu(II), and all tests were conducted without the exclusion of
      atmospheric oxygen. There was no evidence of any significant depolymerization of
      polyacrylamide to free acrylamide monomer, <0.04%. In fact, residual levels of
      acrylamide present already in the low molecular weight polymers were seen to fall
      by 50-80% on heating. Consequently, it is concluded that even if polyacrylamides
      were to contaminate agricultural crops and foods derived therefrom (which itself
      is an unproven suggestion), there is no evidence that the polymers would
      depolymerize on heating of the food to form acrylamide in any significant amount.

PMID- 14582966
TI  - Inhomogeneities in the chemical structure of sugarcane bagasse lignin.
AB  - Sequential treatments of dewaxed bagasse with distilled water, 0.5 M NaOH, 0.5,
      1.0, 1.5, 2.0, and 3.0% H(2)O(2) at pH 11.5, and 2 M NaOH at 55 degrees C for 2 h
      solubilized 2.8, 52.5, 14.9, 3.3, 5.5, 5.0, 2.8, and 2.2% of the original lignin,
      respectively. The eight isolated lignin fractions were subjected to a
      comprehensive structural characterization by UV, FT-IR, and (1)H and (13)C NMR
      spectroscopies and thermal analysis. The nitrobenzene oxidation method was also
      applied to the in situ lignins. The seven lignin fractions, isolated successively
      with alkali and alkaline peroxide, were all SGH-type lignins, with a small amount
      of esterified p-coumaric acid and mainly etherified ferulic acid. No significant
      differences were found in the weight-average molecular weights (1680-2220 g/mol)
      of the seven alkali and alkaline peroxide dissolved lignins. However, the first
      four lignin fractions, isolated with 0.5 M NaOH and 0.5, 1.0, and 1.5% H(2)O(2)
      at pH 11.5, were rich in syringyl units and contained large amounts of
      noncondensed ether structures, whereas the last three lignin fractions, isolated
      sequentially with 2.0 and 3.0% H(2)O(2) at pH 11.5 and 2 M NaOH at 55 degrees C
      for 2 h, had a higher degree on condensation and were rich in guaiacyl lignins.

PMID- 14582967
TI  - Influence of different oligosaccharides and inulin on heterocyclic aromatic amine
      formation and overall mutagenicity in fried ground beef patties.
AB  - The effects of different oligosaccharides [fructooligosaccharide (FOS),
      galactooligosaccharide (GOS), and isomaltooligosaccharide (MOS)] and inulin on
      heterocyclic aromatic amine (HAA) formation and overall mutagenicity in fried
      ground patties were evaluated. Different oligosaccharides and inulin was added
      directly to ground beef. Patties (100 g) were fried at 225 degrees C (surface
      temperature) for 10 min per side. FOS added at levels of 0.5, 1.0, 1.5, 2.0, and
      2.5 g to 100 g of ground beef inhibited total HAA formation by 19, 32, 45, 51,
      and 58%, respectively. The addition of 1.5 g of FOS, GOS, MOS, and inulin to
      ground beef patties inhibited total HAA formation by 50, 47, 46, and 54%,
      respectively. They also reduced overall mutagenicity by 52, 51, 48, and 59%,
      respectively. These studies confirm that oligosaccharides and inulin have the
      potential to reduce HAA formation in cooked beef patties.

PMID- 14582969
TI  - High-performance liquid chromatography (HPLC) analysis of phenolic compounds in
      berries with diode array and electrospray ionization mass spectrometric (MS)
      detection: ribes species.
AB  - High-performance liquid chromatography combined with diode array and electrospray
      ionization mass spectrometric (MS) detection was used to study phenolic compounds
      in berries of black, green, red, and white currants (Ribes spp.). UV-visible
      spectrometry was a valuable tool for the identification of the class of the
      phenolic compound, whereas MS and MS-MS fragmentation data were useful for
      further structural characterization. Distinct similarities were found in the
      relative distribution of conjugated forms of phenolic compounds among the four
      currants. Phenolic acids were found mainly as hexose esters. Flavonol glycosides
      and anthocyanin pigments were mainly found as 3-O-rutinosides and second as 3-O
      glucosides. However, cyanidin 3-O-sambubioside and quercetin hexoside-malonate
      were notable phenolic compounds in red currant. Flavonol hexoside-malonates were
      identified and quantified in the berries of currants for the first time.

PMID- 14582968
TI  - Effects of spraying rare earths on contents of rare Earth elements and effective
      components in tea.
AB  - Rare earth (RE) fertilizer is widely applied in China to increase the yield and
      the quality of crops including tea. However, the effects of spraying RE
      fertilizer on the contents of rare earth elements (REE) and effective components
      in tea are unknown. The results from basin and field experiments show that the
      values of the REE concentrations in new shoots of tea plants and the
      concentration of REE in the soil (REE/REEs) either from control basins or from
      treatment basins were smaller than those in other parts of tea plant and similar
      between control and treatment. The longer the interval between spraying RE
      fertilizer and picking the shoots of tea plants, the less the effects from
      spraying. About 80% summation operator REE (the sum of the concentrations of 15
      REE) in tea, whether it came from spraying or not, was insoluble in the infusion.
      About 10% the soluble REE of summation operator REE in tea infusion was bound to
      polysaccharide, and the amount of REE bound polysaccharide decreased over time.
      At least a 25 day safety interval is needed between spraying and picking if the
      microelement fertilizer is used, in order to enhance tea output and to ensure tea
      safety.

PMID- 14582970
TI  - Value assignment of nutrient and aflatoxin concentrations in standard reference
      material 2387 peanut butter.
AB  - Standard Reference Material (SRM) 2387 peanut butter was recently issued, and the
      process used for value assignment of nutrient and aflatoxin concentrations is
      reported herein. Values were assigned using data provided by the National
      Institute of Standards and Technology (NIST) and collaborating laboratories. SRM
      2387 is intended for use as a primary material for assigning values to in-house
      control materials and for validation of analytical methods for measurements in
      peanut butter and similar high-fat matrixes. SRM 2387 lies in sector 3 of AOAC
      International's fat-protein-carbohydrate triangle. With the addition of SRM 2387,
      NIST now offers materials within-or on the borders between-all sectors of the
      triangle. The Certificate of Analysis for SRM 2387 provides assigned values for
      concentrations of fatty acids, proximates, elements, and total dietary fiber, for
      which product labeling is required by the Nutrition Labeling and Education Act of
      1990, as well as several vitamins, amino acids, and aflatoxins, for which
      labeling is not required. (Aflatoxin levels in peanut butter are regulated by the
      Food and Drug Administration.)

PMID- 14582971
TI  - Seasonal distribution of bromophenols in selected Hong Kong seafood.
AB  - Selected seafood including rabbitfish (Siganus canaliculatus), brown-spotted
      grouper (Epinephelus areolatus), clam (Tapes philippinarum), oyster (Ostrea
      rivularis), shrimp (Penaeus japonicus), and crab (Charybdis feriatus), commonly
      found in the Hong Kong wet market, was monitored for their distribution and
      seasonal variations of their bromophenol contents. Specifically, 2-bromophenol
      (1). 4-bromophenol (2). 2,4-dibromophenol (3). 2,6-dibromophenol (4). and 2,4,6
      tribromophenol (5). were monitored due to their flavor impact to seafood. All
      samples of marine origin contained bromophenols throughout a year. Crab had the
      highest concentration of total bromophenol content throughout the season.
      Concentrations of compounds 1, 4, and 5 in the local seafood were generally
      higher than that found in the literature values to provide characteristic flavor,
      but lower than that required to cause off-flavor. Variations of the flavor impact
      of bromophenols in seafood during a season could be better shown by their flavor
      values. Distribution and seasonal variations of bromophenol content in seafood
      coincided well with the seasonal growth cycle of the bromophenol synthesizing
      seaweeds, e.g. brown algae, in the region suggesting the abundant source of
      bromophenols in the environment might have a high impact on the quantity of
      bromophenols found in seafood.

PMID- 14582972
TI  - GC-ITMS determination and degradation of captan during winemaking.
AB  - Captan and its metabolite tetrahydrophthalimide (THPI) were determined in grapes,
      must, and wine by GC-ITMS. Pesticides were extracted with acetone/petroleum ether
      (50:50 v/v). Because of the high selectivity of the ITMS detector, no interferent
      was found and cleanup was not necessary. Recoveries from fortified grapes, must,
      and wines ranged between 90 and 113% with a maximum coefficient of variation of
      11%. Limits of quantitation were 0.01 mg/kg for both compounds. In model systems,
      captan and its metabolites, THPI, cis-4-cyclohexene-1,2-dicarboxylic acid, and
      1,2,3,6-tetrahydrophthalamic acid, were determined by HPLC. The degradation of
      captan during winemaking was studied. Captan degraded in must, giving 100% THPI,
      and at the end of fermentation, only THPI was found in wine. The degradation of
      captan to THPI was due to the acidity in must and wine. This metabolite was
      present at low levels on grapes, and, unlike captan, it had no negative effect on
      the fermentative process. Model systems showed that the mechanism of
      disappearance of captan in grapes was due to photodegradation and codistillation.

PMID- 14582973
TI  - Dissipation of [(14)C]acetochlor herbicide under anaerobic aquatic conditions in
      flooded soil microcosms.
AB  - Acetochlor degradation was studied under anaerobic conditions representative of
      conditions in flooded soils. Soil-water microcosms were prepared with a saturated
      Drummer clay loam and made anaerobic by either glucose pretreatment or N(2)
      sparging. Sparged microcosms consisted of sulfate-amended, unamended, and gamma
      irradiated microcosms. The microcosms were sampled in triplicate at predetermined
      time intervals during a 371 day incubation period. Volatile, aqueous,
      extractable, and bound (unextractable) (14)C residues were quantified with liquid
      scintillation counting and characterized using high-performance liquid
      radiochromatography (HPLRC) and soil combustion. SO(4)(2)(-), Fe(II), CH(4), and
      pH were monitored. Complete anaerobic degradation of [(14)C]acetochlor was
      observed in all viable treatments. The time observed for 50% acetochlor
      disappearance (DT(50)) was 10 days for iron-reducing and sulfate-reducing
      conditions (sulfate-amended), 15 days for iron-reducing conditions (unamended),
      and 16 days for methanogenic conditions (glucose-pretreated). Acetochlor remained
      after 371 days in the gamma-irradiated microcosms, and metabolites were observed.
      [(14)C]Metabolites were detected throughout the study. Formation of one of the
      metabolites correlated with Fe(II) formation (r(2)(), 0.83). A significant
      portion of the (14)C activity was eventually incorporated into soil-bound residue
      (30-50% of applied acetochlor) in all treatments.

PMID- 14582974
TI  - Reversible and irreversible emission of methanethiol and dimethyl disulfide from
      anaerobically stored broccoli.
AB  - The reversible and irreversible emission of methanethiol (MT) and dimethyl
      disulfide (DMDS) from broccoli florets was demonstrated during anaerobic storage
      at 20 degrees C for up to 24 h. Reversible emission of MT and DMDS was feasible
      only in broccoli stored for between 0 and 12 h under entirely anaerobic
      condition. Beyond that, the emission was completely irreversible. This
      irreversible process was demonstrated through significant reductions in the
      chlorophyll fluorescence values and rate of carbon dioxide production and
      significant increase in the membrane permeability of induced broccoli tissues
      after exposure to air and incubation. Irreversible emission was also demonstrated
      through significant change in color from the characteristic bright green to olive
      green as well as the conversion of chlorophyll a to pheophytin a and chlorophyll
      a' contents of the induced florets after hot-water treatment. These findings
      suggest that the irreversible emission of MT and DMDS is a function of permanent
      membrane damage and loss of intracellular compartmentation in the broccoli
      tissues as a result of the anaerobic induction. The off-odor formation can still
      be reversed if the affected tissue is only temporarily impaired by anaerobic
      condition, thereby maintaining the quality of stored broccoli.

PMID- 14582976
TI  - Identification of the taste enhancer alapyridaine in beef broth and evaluation of
      its sensory impact by taste reconstitution experiments.
AB  - An essential compound imparting the sweet taste to beef broth was investigated.
      Taste activity-guided fractionation of beef broth by ultrafiltration, gel
      permeation chromatography, and HPLC in combination with the recently developed
      comparative taste dilution analysis enabled the localization of a fraction
      possessing sweetness-enhancing activity upon degustation. Comparison of the
      chromatographic, spectroscopic, and sensory data with those of the synthetic
      reference compound led to the identification of the sweetness-enhancing N-(1
      carboxyethyl)-6-(hydroxymethyl)pyridinium-3-ol inner salt, named alapyridaine,
      which was recently isolated from heated aqueous solutions of hexoses and l
      alanine. After quantification of alapyridaine in beef broth, sensory analysis of
      synthetic beef taste recombinates spiked with synthetic alapyridaine in its
      "natural" concentration of 419 mug/L and comparison to the taste quality of a
      tastant recombinate lacking the alapyridaine revealed a significant increase in
      sweetness and umami character only when the alapyridaine was present in the
      recombinate. These data demonstrate for the first time that, in "natural"
      concentrations, the alapyridaine exhibited a pronounced effect on the overall
      taste quality of beef broth, in particular, on the sweet and umami character.

PMID- 14582977
TI  - Characteristic aroma components of rennet casein.
AB  - Rennet casein, produced by enzymatic (rennet) precipitation of casein from
      pasteurized skim milk, is used in both industrial (technical) and food
      applications. The flavor of rennet casein powder is an important quality
      parameter; however, the product often contains an odor described as like that of
      animal/wet dog. Two commercial rennet casein powders were evaluated to determine
      the compounds responsible for the typical odor. Aroma extracts were prepared by
      high-vacuum distillation of direct solvent (ether) extracts and analyzed by gas
      chromatography-olfactometry (GCO), aroma extract dilution analysis (AEDA), and GC
      mass spectrometry (MS). Odorants detected by GCO were typical of those previously
      reported in skim milk powders and consisted mainly of short-chain volatile acids,
      phenolic compounds, lactones, and furanones. Results of AEDA indicated o
      aminoacetophenone to be a potent odorant; however, sensory descriptive sensory
      analysis of model aroma systems revealed that the typical odor of rennet casein
      was principally caused by hexanoic acid, indole, guaiacol, and p-cresol.

PMID- 14582975
TI  - Evolution of chemical and sensory properties during aging of top-fermented beer.
AB  - The aging and consequent changes in flavor molecules of a top-fermented beer were
      studied. Different aging conditions were imposed on freshly bottled beer. After 6
      months of aging, the concentration changes were recorded for acetate esters,
      ethyl esters, carbonyls, Maillard compounds, dioxolanes, and furanic ethers. For
      some flavor compounds, the changes with time of storage were monitored at
      different temperatures, either with CO(2) or with air in the headspace of the
      bottles. For some molecules a relationship was determined between concentration
      changes and sensory evaluation results. A decrease in volatile esters was
      responsible for a reduced fruity flavor during aging. On the contrary, various
      carbonyl compounds, some ethyl esters, Maillard compounds, dioxolanes, and
      furanic ethers showed a marked increase, due to oxidative and nonoxidative
      reactions. A very high increase was found for furfural, 2-furanmethanol, and
      especially the furanic ether, 2-furfuryl ethyl ether (FEE). For FEE a flavor
      threshold in beer of 6 mug/L was determined. In the aged top-fermented beer, FEE
      concentrations multiple times the flavor threshold were observed. This was
      associated with the appearance of a typical solvent-like flavor. As the FEE
      concentration increased with time at an almost constant rate, with or without air
      in the headspace, FEE (and probably other furanic ethers) is proposed as a good
      candidate to evaluate the thermal stress imposed on beer.

PMID- 14582978
TI  - Extraction of essential oil and pigments from Curcuma longa [L] by steam
      distillation and extraction with volatile solvents.
AB  - Curcuma longa [Linn] (turmeric), of the Zingiberaceae family, has a great
      importance in the food, textile, and pharmaceutical industries. The aim of this
      work was to identify the best processing conditions to maximize the yields of
      essential oil and pigments, as well as their content of ar-turmerone, (alpha and
      beta)-turmerone, and the curcuminoids, respectively. Autoclave pressure and
      distillation time were the variables studied for the steam distillation process.
      The highest yields of essential oil (0.46 wt %) and pigment (0.16 wt %)-expressed
      as curcumin, demethoxycurcumin, and bisdemethoxycurcumin-were obtained at a
      pressure of 1.0 x 10(5) Pa and a time of 2 h. On the other hand, with extraction
      by volatile solvents, the best yield of essential oil (5.49 wt %) was obtained
      when using 0.175, 0.124, 0.088 mm particles (Foust, A. S.; Wenzel, L. A.; Clump,
      C. W.; Maus, L.; Andersen, L. B. Principios das Operacoes Unitarias; Editora
      Guanabara Dois S.A.: Rio de Janeiro, Brazil, 1982), at 40 degrees C, and 6 h of
      extraction. However, the best yield of pigment (7.98 wt %) was obtained under the
      same conditions, except for the temperature (30 degrees C).

PMID- 14582979
TI  - Phosphorylation of egg white proteins by dry-heating in the presence of
      phosphate.
AB  - Food proteins were phosphorylated by heating in a dry state in the presence of
      phosphate. When casein, whey protein isolate (WPI), and egg white proteins (EWP),
      which were lyophilized from their solutions in a phosphate buffer, were dry
      heated at various temperatures and pH levels for 1-5 days, EWP was more highly
      phosphorylated than casein and WPI. Phosphorylation of EWP was promoted with a
      decrease of pH from 7.0 to 3.0 when the incubation temperature was raised from 55
      to 100 degrees C. The phosphorus content of EWP increased from 0.08 to 0.64% by
      dry-heating at pH 3.0 and 85 degrees C for 5 days in the presence of phosphate.
      The electrophoretic mobility of EWP increased with an increase in the
      phosphorylation level. The heat-induced polymerization of EWP by dry-heating was
      not affected by the presence of phosphate. Although the solubility of EWP
      decreased by dry-heating at pH 3.0-5.5, the phosphorylation depressed the
      insolubilization at low pH. The phosphate bonds in phosphorylated EWP (P-EWP)
      were stable at pH 2.0-10.0 and were more acid-labile and base-stable than
      phosphoesters of egg riboflavin-binding protein (RfBP). (31)P NMR spectral data
      suggested that besides phosphoesters, phosphodiester and polyphosphate bonds were
      introduced in P-EWP. Heat stability of EWP was improved, and calcium phosphate
      solubilizing ability of EWP was enhanced by phosphorylation.

PMID- 14582981
TI  - Rapid digestion of Cry34Ab1 and Cry35Ab1 in simulated gastric fluid.
AB  - Two genes were identified in Bacillus thuringiensis Berliner (Bt) that code for
      the proteins that comprise a Cry34Ab1/Cry35Ab1 binary insecticidal crystal
      protein. Maize, Zea mays L., plants have been transformed to express the
      Cry34Ab1/Cry35Ab1 proteins, and as a result, these plants are resistant to attack
      by western corn rootworm, Diabrotica virgifera virgifera LeConte, a major pest in
      the Midwestern corn-growing area of the U.S.A. As part of the safety assessment
      for the proteins, digestibility studies were conducted. Digestion experiments
      with both proteins demonstrated rapid degradation in simulated gastric fluid,
      comparable to other registered plant-incorporated protectants. Quantitative and
      qualitative approaches for determining digestibility are illustrated.

PMID- 14582980
TI  - Effect of the number of flavanol units on the antioxidant activity of procyanidin
      fractions isolated from chocolate.
AB  - Of three different solvents (acetone, ethanol, and methanol) mixed with water and
      acetic acid, the acetone/water/acetic acid mixture (70:28:2, v/v) proved to be
      best for extracting dark-chocolate procyanidins. High-performance liquid
      chromatography coupled with electrospray ionization mass spectrometry (HPLC-MS
      ESI) was further used to identify oligomers found in the extract. After HPLC
      fraction collection, the reduction power of flavanoid fractions was measured in
      the AAPH [2,2'-azobis(2-amidinopropane)dihydrochloride] assay, where oxidation of
      linoleic acid is induced in an aqueous dispersion. Even expressed in relative
      monomeric efficiency units, the oxidation-inhibiting power of polymerized
      oligomers is much stronger than that of monomers. A comparison with 10 usual
      antioxidants indicated that oligomers with three or more (epi)catechin units are
      by far the most efficient.

PMID- 14582982
TI  - Interactions of soluble peptides and proteins from skeletal muscle on the release
      of volatile compounds.
AB  - The ability of skeletal dipeptides (carnosine and anserine) and a sarcoplasmic
      protein (myoglobin) to interact with key flavor compounds (hexanal, octanal,
      methional, 2-pentanone, 2-methylbutanal, and 3-methylbutanal) has been studied
      using the solid phase microextraction (SPME) technique. Conditions for SPME
      analysis (fiber coating, sampling time, and linearity of detection) were
      optimized. The effect of pH on the binding was also investigated. Thermodynamic
      models were applied to evaluate the binding parameters n (number of binding
      sites), K (affinity constant), and DeltaG (Gibb's free energy) to all of the
      flavor compounds studied, and they showed an absence of cooperative effect.
      Carnosine was the peptide with the highest affinity for all of the volatile
      compounds except 2-pentanone. Its interaction with hexanal and methional was
      significantly affected by pH. Anserine showed a lower level of interactions with
      hexanal, methional, 2-methylbutanal, and 3-methylbutanal, whereas myoglobin
      interacted with only hexanal and 2-methylbutanal. Differences in aroma retention
      can thus result in different sensory perceptions of muscle foods.

PMID- 14582983
TI  - Radiation-induced enhancement of nitrite reducing activity of cytochrome c.
AB  - Commercial cytochrome c (Cyt c) was irradiated with Co-60 gamma-rays in the dose
      range of up to 3.0 kGy to investigate the enhancement of the nitrite reducing
      activity of Cyt c. The optimum irradiation dose to induce nitrite reducing
      activity for 30 muM Cyt c solution was 1.0 kGy under an O(2) atmosphere. The
      nitrite reducing activity of Cyt c irradiated at this dose was approximately 45
      fold that of unirradiated Cyt c and ca. 1.2-fold that of nitrite reductase. The
      irradiation treatment resulted in unfolding of the peptide chain, exposure of the
      heme group, oxidation of methionine to methionine sulfoxide, dissociation of the
      sixth ligand (Met), and occurrence of autoxidation in Cyt c. Sepharose
      immobilized irradiated Cyt c had a similar activity to that in solution. The
      resin retained the activity after five uses even after 1 year of storage. The
      irradiated Cyt c will be able to be used as a substitute for nitrite reductase.

PMID- 14582984
TI  - Compost as a soil supplement increases the level of antioxidant compounds and
      oxygen radical absorbance capacity in strawberries.
AB  - Compost as a soil supplement significantly enhanced levels of ascorbic acid (AsA)
      and glutathione (GSH) and ratios of AsA/dehydroascorbic acid (DHAsA) and
      GSH/oxidized glutathione (GSSG) in fruit of two strawberry (Fragaria x ananassa
      Duch.) cultivars, Allstar and Honeoye. The peroxyl radical (ROO(*)) as well as
      the superoxide radical (O(2)(*)(-)), hydrogen peroxide (H(2)O(2)), hydroxyl
      radical (OH(*)), and singlet oxygen ((1)O(2)) absorbance capacity in strawberries
      increased significantly with increasing fertilizer strength and compost use. The
      planting medium (compost) x fertilizer interaction for phenolics and flavonoids
      was significant. Fruit from plants grown in full-strength fertilizer with 50%
      soil plus 50% compost and 100% compost yielded fruit with the highest levels of
      phenolics, flavonol, and anthocyanin content. A positive relationship between
      antioxidant activities and contents of AsA and GSH and ratios of AsA/DHAsA and
      GSH/GSSG existed in fruit of both strawberry cultivars. Correlation coefficients
      for the content of antioxidant components versus antioxidant activity [against
      ROO(*), O(2)(*)(-), H(2)O(2), OH(*), or (1)O(2)] ranged from r( )()= 0.7706 for
      H(2)O(2) versus GSH/GSSH in cv. Allstar to r = 0.9832 for O(2)(*)(-) versus total
      flavonoids in cv. Allstar.

PMID- 14582985
TI  - Copper-catalyzed oxidation of a structured lipid-based emulsion containing alpha
      tocopherol and citric acid: influence of pH and NaCl.
AB  - The effects of salt and pH on copper-catalyzed lipid oxidation in structured
      lipid-based emulsions were evaluated. Ten percent oil-in-water emulsions were
      formulated with a canola oil/caprylic acid structured lipid and stabilized with
      0.5% whey protein isolate. alpha-Tocopherol and citric acid were added to the
      emulsions to determine how changes in pH or the addition of NaCl affected their
      antioxidant activity. The peroxide values and anisidine values of emulsions
      stored at 50 degrees C were measured over an 8-day period. Increased lipid
      oxidation occurred in the pH 7.0 emulsions and when 0.5 M NaCl was added to the
      pH 3.0 samples. Adding alpha-tocopherol, citric acid, or a combination of the two
      compounds slowed the formation of hydroperoxides and their subsequent
      decomposition products in pH 3.0 emulsions.

PMID- 14582986
TI  - Effects of alpha-tocopherol, beta-carotene, and soy isoflavones on lipid
      oxidation of structured lipid-based emulsions.
AB  - Structured lipids (SLs) are triacylglycerols that have been modified to change
      the fatty acid composition and/or positional distribution in the glycerol
      backbone by chemically and/or enzymatically catalyzed reactions and/or genetic
      engineering. Ten percent oil-in-water emulsions were formulated with a canola
      oil/caprylic acid SL and stabilized with 0.5% whey protein isolate (WPI) or
      sucrose fatty acid ester (SFE). The effects of alpha-tocopherol, beta-carotene,
      genistein, and daidzein (added at 0.02 wt % of oil) on lipid oxidation were
      evaluated over a 15-day period in emulsion samples. Significantly (p < 0.05) less
      total oxidation (calculated from peroxide value and anisidine value measurements)
      occurred in the WPI emulsions compared to their SFE counterparts. In this study,
      alpha-tocopherol, beta-carotene, and both soy isoflavones exhibited prooxidant
      activities in SFE emulsions. Because of their ability to exhibit prooxidant
      activity under certain conditions, manufacturers must experiment with these
      compounds before adding them to SL-based products as functional ingredients.

PMID- 14582987
TI  - Activity-guided identification of a chemopreventive compound in coffee beverage
      using in vitro and in vivo techniques.
AB  - The aim of the present study was to apply an activity-guided screening procedure
      to coffee brew to identify a key chemopreventive compound by means of in vitro
      antioxidant tests as well as cell culture experiments and to prove the in vivo
      activity of that compound by an animal feeding experiment. Solvent fractionation,
      followed by multiple-step ultrafiltration, revealed that the polar coffee
      compounds with molecular weights below 1 kDa show the major inhibitory effect on
      the in vitro peroxidation of linoleic acid as well as the predominant
      chemopreventive enzyme modulating activity on the NADPH-cytochrome c reductase
      (CCR) and glutathione S-transferase (GST) in human intestinal Caco-2 cells. To
      identify the chemical structure of the most active antioxidants and
      chemopreventive compounds, the polar compounds were further separated by HPLC
      techniques, followed by the activity-guided screening of the individual HPLC
      fraction. These experiments demonstrated 5-chlorogenic acid to be the most
      powerful antioxidant in vitro, whereas, in contrast, chemopreventive effects on
      the GST activity were found for the N-methylpyridinium ion, the structure of
      which was elucidated by LC-MS and NMR experiments and confirmed by synthesis. The
      in vivo activities of coffee beverage and N-methylpyridinium ions were tested in
      a 15-day feeding experiment on rats. In the liver, feeding of 4.5% coffee
      beverage resulted in increases of GST and UDP-GT activities by 24 and 40%
      compared to animals fed the control diet (p > 0.05), respectively. Plasma total
      antioxidant capacity and plasma tocopherol were elevated in animals fed the
      coffee beverage and the N-methylpyridinium-containing diet. In summary, the
      results demonstrating a strong in vitro antioxidant activity for coffee were
      confirmed by the feeding study. Surprisingly, feeding of N-methylpyridinium also
      resulted in an increased total antioxidant capacity in the plasma. The data
      indicate that the mode of action demonstrated for N-methylpyridinium in
      biological systems is different from that in foods.

PMID- 14582989
TI  - Significance of preslaughter stress and different tissue PUFA levels on the
      oxidative status and stability of porcine muscle and meat.
AB  - Polyunsaturated fatty acids (PUFAs) and exercise-induced stress are known to
      increase the oxidative susceptibility of lipids in muscle tissue. In contrast,
      antioxidative enzymes, e.g., catalase, superoxide dismutase, and glutathione
      peroxidase, are known to help sustain the delicate oxidative balance in
      biological tissue upon the application of stressors. The present study
      investigates the combined effect of different diet-induced muscle PUFA contents
      and preslaughter stress on the activity of antioxidative muscle enzymes and the
      oxidative stability of cooked meat. An increased content of unsaturated fatty
      acids in the tissue led to a decreased activity of lactate dehydrogenase in the
      plasma, indicating increased cell integrity. Catalase activity in the muscle
      tissue increased with increasing PUFA levels. However, this upregulation in
      antioxidative status of the muscle could not counteract the subsequent
      development of accelerated lipid oxidation in cooked meat as measured in terms of
      thiobarbituric acid reactive substances. Moreover, preslaughter stress induced
      increasing oxidative changes with elevated PUFA levels in the muscle tissue.

PMID- 14582988
TI  - Conjugated linoleic acids alter the fatty acid composition and physical
      properties of egg yolk and albumen.
AB  - Effects of dietary conjugated linoleic acids (CLAs) and docosahexaenoic acid
      (DHA) on the fatty acid composition of different egg compartments after storage
      were studied. Four dietary treatments [supplemented with safflower oil (SAFF,
      control group), DHA, CLAs plus DHA (CAD), and CLAs alone] were administered to
      Single Comb White Leghorn (SCWL) laying hens. Eggs from the different treatment
      groups were collected and stored for 10 weeks at 4 degrees C before analysis.
      Fatty acids from the yolk (yolk granules and plasma), egg albumen, and vitelline
      membrane were analyzed by gas chromatography. The yolk of eggs from hens given
      CLAs had significantly higher amounts of saturated fatty acids, typically 16:0
      and 18:0, but lower amounts of polyunsaturated fatty acids (PUFAs) compared to
      eggs from the control group (SAFF). CLA content was highest in the yolk and
      present in both neutral and polar lipids, with the greatest concentrations in
      neutral lipids. DHA was incorporated mainly into yolk polar lipids. Lipids in
      yolk plasma and granules contained similar amounts of CLAs. The fatty acid
      compositions of vitelline membrane and egg albumen mirrored that of the egg yolk.
      CLA supplementation resulted in hard and rubbery yolks when compared to hard
      cooked eggs from the control group. This study showed that feeding CLAs to hens
      led to accumulation of the isomers in polar and neutral lipids of the egg yolk
      and that these isomers migrated into egg albumen. Because the sensory properties
      of hard-cooked eggs were negatively affected by the enrichment of a mixture of
      CLA isomers in this study, further research should be conducted to evaluate how
      the different isomers alter the properties of egg yolk and albumen so that the
      quality of designed eggs containing CLAs and DHA can be improved.

PMID- 14582990
TI  - Positional effect on protein and oil content and composition of soybeans.
AB  - Soybean (Glycine max [L.] Merr.) protein and oil qualities, with respect to
      monogastric nutrition, have been linked to the relative abundance of specific
      protein subunits and fatty acids, respectively. An analysis of field-grown
      soybean seeds by near-infrared spectroscopy revealed significant differences in
      their protein and oil contents as a function of nodal position. Seed proteins
      from the plant apex were high in protein and low in oil content, while those from
      the basal region exhibited an opposite pattern of accumulation. Sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis of total seed proteins revealed that
      the beta-subunit of beta-conglycinin content was 4-fold higher in seeds from the
      apical nodes than in seeds from basal nodes. The glycinin A3 polypeptide content
      gradually increased in successively lower nodes from the top of the plant. Its
      accumulation was drastically reduced when nitrogen was applied at specific growth
      stages. Exogenous nitrogen did not alter the pattern of beta-subunit
      accumulation, but accrual of the acidic and basic polypeptides of glycinin was
      diminished. The remaining seed storage protein components were not influenced by
      nodal position or nitrogen application. Gas chromatographic analysis of fatty
      acids indicated that only oleic (18:0) and linoleic (18:2) acids showed
      variability in accumulation at different nodes. Neither the abundance nor the
      distribution of the fatty acids was altered by nitrogen application.

PMID- 14582991
TI  - Antioxidant and antiproliferative activities of strawberries.
AB  - Strawberries contain high levels of antioxidants, which have been correlated with
      a decreased risk of chronic disease. To more fully characterize the antioxidant
      profiles and possible associated health benefits of this fruit, the total free
      and bound phenolic, total flavonoid, and total anthocyanin contents of eight
      strawberry cultivars (Earliglow, Annapolis, Evangeline, Allstar, Sable, Sparkle,
      Jewel, and Mesabi) were measured. Cultivar effects on phenolic contents were
      compared with antioxidant capacities, as measured by the total oxyradical
      scavenging capacity (TOSC) assay, and to antiproliferative activities, as
      measured by inhibition of HepG(2) human liver cancer cell proliferation in vitro.
      Free phenolic contents differed by 65% between the highest (Earliglow) and the
      lowest (Allstar) ranked cultivars. The water soluble bound and ethyl acetate
      soluble bound phenolic contents averaged 5% of the total phenolic content of the
      cultivars. The total flavonoid content of Annapolis was 2-fold higher than that
      of Allstar, which had the lowest content. The anthocyanin content of the highest
      ranked cultivar, Evangeline, was more than double that of the lowest ranked
      cultivar, Allstar. Overall, free phenolic content was weakly correlated with
      total antioxidant activity, and flavonoid and anthocyanin content did not
      correlate with total antioxidant activity. The proliferation of HepG(2) human
      liver cancer cells was significantly inhibited in a dose-dependent manner after
      exposure to all strawberry cultivar extracts, with Earliglow exhibiting the
      highest antiproliferative activity and Annapolis exhibiting the lowest. No
      relationship was found between antiproliferative activity and antioxidant
      content.

PMID- 14582992
TI  - Urinary excretion of 5-(3',4'-dihydroxyphenyl)-gamma-valerolactone, a ring
      fission metabolite of (-)-epicatechin, in rats and its in vitro antioxidant
      activity.
AB  - There is great interest in the nutritional potential of (-)-epicatechin, a common
      polyphenolic constituent of many foods and beverages, because of its potent
      antioxidant capacity. To better evaluate the biological role of (-)-epicatechin,
      we studied the urinary excretion of 5-(3',4'-dihydroxyphenyl)-gamma
      valerolactone, a ring-fission metabolite of (-)-epicatechin by intestinal
      microflora, in rats as well as its antioxidant activity in vitro. The method for
      measuring the urinary levels of (-)-epicatechin and 5-(3',4'-dihydroxyphenyl)
      gamma-valerolactone was based on the enzymatic hydrolysis of beta-glucuronidase
      and sulfatase, and was subsequently determined by HPLC coupled to an
      electrochemical detector. Following administration of (-)-epicatechin at doses of
      0, 20, 40, and 80 mumol per rat, (-)-epicatechin and 5-(3',4'-dihydroxyphenyl)
      gamma-valerolactone were excreted into the urine within 24 h in a dose-dependent
      manner. Urinary 5-(3',4'-dihydroxyphenyl)-gamma-valerolactone was mostly in the
      conjugated form, with a higher ratio of conjugation than (-)-epicatechin. We
      assessed the relative antioxidant potentials for scavenging radicals in the
      aqueous phase as expressed in the Trolox equivalent antioxidant capacity (TEAC).
      The results demonstrated that the degradation of (-)-epicatechin into 5-(3',4'
      dihydroxyphenyl)-gamma-valerolactone attenuated the antioxidant ability of the
      former. However, 5-(3',4'-dihydroxyphenyl)-gamma-valerolactone showed stronger
      antioxidant activity than l-ascorbic acid. These results led us to suppose that 5
      (3',4'-dihydroxyphenyl)-gamma-valerolactone, a microbial metabolite of (-)
      epicatechin, circulating in the body may also at least be biologically active in
      terms of contributing to its combined antioxidant effect.

PMID- 14582993
TI  - Effects of chronic ingestion of ochratoxin a on blood levels and excretion of the
      mycotoxin in sheep.
AB  - Ruminants are relatively resistant to the acutely toxic effects of ochratoxin A,
      due to extensive degradation of ochratoxin A to its less toxic metabolite
      ochratoxin alpha by rumen microorganisms. However, most estimates of the
      degradation capacity for ochratoxin A in ruminants are based on in vitro studies.
      In the current study, the metabolism of ochratoxin A was investigated over a
      period of 29 days, feeding various doses of the mycotoxin (0, 9.5, 19.0, and 28.5
      mug ochratoxin A/kg body weight) to sheep. Animals were fed diets consisting of
      70% concentrates and 30% grass silage. Significant concentrations of undegraded
      ochratoxin A were detected in serum of sheep at all levels of ochratoxin A
      tested. Serum concentrations of ochratoxin A slightly accumulated with time of
      exposure and were linearly dependent on the administered dose of ochratoxin A.
      Furthermore, a constant proportion (6-8%) of the dose was excreted in the urine.
      The results of this study indicate that even at moderate to low levels of
      ochratoxin A in the diet, considerable amounts of the mycotoxin are absorbed by
      ruminants and may accumulate in tissues. Therefore, feeding of ochratoxin A
      contaminated feedstuffs to ruminants does not seem to be a reliable means for
      using these feedstuffs.

PMID- 14582994
TI  - Prevention of patulin toxicity on rumen microbial fermentation by SH-containing
      reducing agents.
AB  - Patulin, a toxic fungal metabolite, negatively affects rumen fermentation. This
      mycotoxin has also been associated with intoxication cases in cattle. This study
      investigates the use of SH-containing reducing compounds to prevent patulin's
      negative effects on the rumen microbial ecosystem. The effect of 50 microg/mL
      patulin on the fermentation of alfalfa hay was measured in batch cultures with
      and without reducing agents. Sulfhydryl-containing cysteine and glutathione
      prevented the negative effects of the toxin on dry matter degradation, gas, and
      volatile fatty acid production (P < 0.01). However, non-sulfhydryl-containing
      ascorbic and ferulic acids did not protect against patulin's toxicity (P > 0.01).
      Patulin was unstable in buffered rumen fluid as the concentration decreased by
      half after 4 h of incubation. In the presence of sulfhydryl groups, the toxin
      disappeared rapidly and was not detected after 1 h of incubation. The utilization
      of sulfhydryl-containing compounds such as cysteine to avert patulin toxicity
      could have practical implications in ruminant nutrition.

PMID- 14582997
TI  - Measurement and ab initio calculation of CSA/dipole-dipole cross-correlated
      relaxation provide insight into the mechanism of a H2-forming dehydrogenase.
AB  - Using transferred cross-correlated relaxation and DFT calculations, the
      conformation of the relevant conformation of N5,N10
      methylenetetrahydromethanopterin, a reaction intermediate bound to the 80 kD H2
      forming N5,N10-methylenetetrahydromethanopterin dehydrogenase is determined. The
      conformation of the intermediate differs from the free form in solution and makes
      the reaction mechanism plausible.

PMID- 14582996
TI  - Shape-adaptable water-soluble conjugated polymers.
AB  - Cationic water-soluble conjugated polymers with a non "rigid-rod" aspect ratio
      can be prepared by Suzuki coupling condensation polymerization of 2,7-dibromo-9,9
      bis(6'-bromohexyl)fluorene and varying ratios of p- and m-phenyl diboronic acids,
      followed by reaction with trimethylamine. The resulting polymers are designated
      MnPm+, where the subscripts in Mn and Pm correspond to the ratio of meta and para
      linkages, respectively. Absorption and fluorescence spectra indicate facile
      energy transfer via interachain or intrachain mechanisms. The emission of MnPm+
      with m > 50 matches that of M0P100+. Excitations ultimately reside in the polymer
      segments with largest number of para linkages. FRET experiments show that the
      polymers with a more flexible structure are better donors to fluorescein-labeled
      double-stranded DNA. Similar results are obtained when intercalated ethidium
      bromide is used as the acceptor. These results indicate that there is better
      spatial registry between the flexible conjugated polymers and the secondary
      structure of DNA.

PMID- 14582998
TI  - Self-assembly approach toward magnetic silica-type nanoparticles of different
      shapes from reverse block copolymer mesophases.
AB  - In the present study poly(isoprene-block-ethylene oxide), PI-b-PEO, block
      copolymers are used to structure iron oxide and silica precursors into reverse
      mesophases, which upon dissolution of the organic matrix lead to well-defined
      nanoparticles of spheres, cylinders, and plates based on the original structure
      of the mesophase prepared. The hybrid mesophases with sphere, cylinder, and
      lamellar morphologies containing the inorganic components in the minority phases
      are characterized through a combination of small-angle X-ray scattering (SAXS),
      transmission electron microscopy (TEM), scanning transmission electron microscopy
      (STEM), and electron energy loss spectroscopy (EELS). After heat treatments the
      respective nanoparticles on mica surfaces are characterized by scanning force
      microscopy (SFM). X-ray diffraction (XRD) and superconducting quantum
      interference device (SQUID) magnetometer measurements are performed to
      demonstrate that the heat treatment leads to the formation of a magnetic gamma
      Fe2O3 crystalline phase within the amorphous aluminosilicate. The results pave
      the way to functional, i.e., magnetic nanoparticles where the size, shape, and
      iron oxide concentration can be controlled opening a range of possible
      applications.

PMID- 14582999
TI  - Water molecules in the schiff base region of bacteriorhodopsin.
AB  - The Schiff base region of bacteriorhodopsin (BR), a light-driven proton pump,
      contains a pentagonal cluster, being composed of three water molecules and one
      oxygen each of Asp85 and Asp212. Asp85 and Asp212 are located at similar
      distances from the retinal Schiff base, whereas the Schiff base proton is
      transferred only to Asp85 during the pump function. The present FTIR study
      experimentally established the stretching vibration of water402 hydrating with
      Asp85 by use of various BR mutants, whose frequency (2171 cm-1 as the O-D
      stretch) indicates very strong hydrogen bond.

PMID- 14583000
TI  - Constructing a stable carbene with a novel topology and electronic framework.
AB  - The perimidine skeleton provides a framework for the isolation of a novel, stable
      carbene possessing a unique molecular architecture and electronic structure. The
      remarkable steric environment and exceptional electron-donating ability for the
      carbene-carbon are revealed through structural and spectroscopic characterization
      of the parent carbene and two sterically encumbered rhodium-carbene complexes,
      L2RhCl{C[NCH(CH3)2]2(C10H6)} (5 L2 = COD; 6 L = CO).

PMID- 14583001
TI  - Dealkylation of organotin compounds by biological dithiols: toward the chemistry
      of organotin toxicity.
AB  - In this Communication, we report evidence for the dealkylation of trialkyltin
      compounds by a short linear peptide extracted from a small membrane protein
      (stannin) involved in cellular apoptosis and containing a CXC motif. We show that
      (a) organotin binding induces the formation of a beta-turn in the linear peptide,
      (b) both cysteines are necessary for the dealkylation reaction, and (c) stable
      1:1 complexes are formed between the peptide and diorganotins that can be
      observed by ESI-MS. Organotin degradation by biological dithiols may be
      responsible for both the delayed activity of these toxins in humans and the
      organotin resistance mechanisms in bacteria.

PMID- 14583002
TI  - Possible lowest-energy geometry of silicon clusters Si21 and Si25.
AB  - Possible lowest-energy structures of Si21 and Si25 are found on the basis of the
      starting structures obtained via the global search for nearly identical low
      energy Stillinger-Weber (SW) and modified-SW structures. The fact that the lowest
      energy structures are spherical-like may suggest that the prolate-to-spherical
      like structural transition for the silicon cluster Sin is likely to occur in the
      range of 21 < n < 25.

PMID- 14583003
TI  - Self-sustaining peristaltic motion on the surface of a porous gel.
AB  - We report the structural color behavior of a periodic ordered mesoporous gel
      synchronized with the Belousov-Zhabotinsky (BZ) reaction. The structural colored
      concentric rings which were spatiotemporally spread out on the porous gel were
      observed during the BZ reaction. The color tone of the structural color, which is
      determined by the swelling ratio of the gel, was periodically changed. This is
      the first evidence that a self-sustaining peristaltic motion occurs on the
      surface of a gel.

PMID- 14583004
TI  - Toward artificial developmental regulators.
AB  - A polyamide-peptide conjugate is designed which recruits sequence specifically
      the developmental regulator Exd to a cognate DNA site. In particular, an eight
      ring hairpin polyamide (Im-Im-Py(C3H6NHR)-Py-gamma-Im-Py-Py-Py-beta-Dp) with a
      heptapeptide (R = Ac-Phe-Tyr-Pro-Trp-Met-Lys-Gly-) attached on a central ring was
      shown to induce cooperative binding of the Drosophila Hox protein cofactor Exd
      with a Kd of 4.4 nM in vitro, an order of magnitude more efficient than the
      natural Hox protein partner Ubx. The conjugate joins two sequence specific
      domains, one for DNA and one for the protein. This small molecule thus serves as
      a cooperative protein-DNA dimerizer, which mimics the natural Hox family of
      developmental regulators.

PMID- 14583005
TI  - Stable lanthanide luminescence agents highly emissive in aqueous solution:
      multidentate 2-hydroxyisophthalamide complexes of Sm(3+), Eu(3+), Tb(3+), Dy(3+).
AB  - Efficient lanthanide (Ln) luminescent probes require good ligand-to-metal energy
      transfer and high aqueous stability. A family of ligands based on 2
      hydroxyisophthalamide chelating units is reported. These form highly stable,
      eight-coordinate Ln complexes. Several of these (Ln = Sm, Eu, Tb, Dy) emit in the
      visible region with good ligand-to-lanthanide energy transfer. The absolute
      quantum yields of the two Tb complexes studies (Phi = 0.59, 0.61) and high
      absorbance make these the brightest luminescent probes for time-resolved
      detection; the emission spectrum of one complex can be seen down to 10-15 M. The
      low overlap of the four different Ln complexes enables their simultaneous
      detection and discrimination.

PMID- 14583006
TI  - A convenient one-pot procedure to afford bicyclic molecules by stereospecific
      iron carbonyl mediated [6 + 2] ene-type cyclization: a possible approach to
      gelsemine.
AB  - A convenient one-pot procedure to prepare angularly substituted bicyclic and
      tricyclic molecules with excellent diastereoselectivity in good yield was
      developed, by Fe(CO)5 promoted cyclization. Three transformations (complexation,
      isomerization, and cyclization) were realized in a single operation. The product
      of this reaction may be a precursor for synthesis of the alkaloid gelsemine.

PMID- 14583007
TI  - Tetrasilatetrahedranide: a silicon cage anion.
AB  - The first silicon cage anion,
      tris{bis[bis(trimethylsilyl)methyl](methyl)silyl}tetrasilatetrahedranide (6-),
      has been synthesized by the reaction of
      tetrakis{bis[bis(trimethylsilylmethyl](methyl)silyl}tetrasilatetrahedrane with
      potassium graphite in diethyl ether by reductive cleavage of exocyclic Si-Si
      bond. The structural characterization of K+(18-crown-6).6- has been achieved by X
      ray crystallography, showing that 6- is a separated ion pair and the
      tetrasilatetrahedranide moiety has a significantly distorted tetrahedrane
      skeleton containing one inverted tetrahedral (umbrella type) silicon atom. The
      four silicon atoms in the Si4 skeleton are equivalent on the NMR time scale due
      to the migration of the Dis2MeSi substituent.

PMID- 14583008
TI  - Contact ion pair between Na+ and PtCl(6)(2-) favored in methanol.
AB  - Ion-pair formation between a Na+ cation and the [PtCl62-] anion in methanol is
      observed from195Pt NMR chemical shift trends as well as from molecular dynamics
      computer simulations. Free energy of association calculations reveal that contact
      ion pairs (CIPs) are the most favored configuration in methanol, followed by
      solvent shared ion pairs (SSHIPs). By contrast, such ion-pair formation is not
      observed for comparable solutions in water.

PMID- 14583009
TI  - Dicopper-[18]ane-N6 complex as the platform for phosphate monoester binding.
AB  - Dicopper-[18]ane-N6 complex functions as a broad spectrum receptor for phosphate
      monoesters.

PMID- 14583010
TI  - Spin crossover of spiro-biphenalenyl neutral radical molecular conductors.
AB  - We present ab initio molecular and solid-state calculations at the level of
      density functional theory (DFT) for the ethyl-substituted spiro-biphenalenyl
      neutral radical organic conductor. We find that the phase transition of this
      material is accompanied by a spin crossover (low-spin, LS, to high-spin, HS), and
      consequently a different band becomes the conduction band. The energy gap (Eg)
      increases from 0.12 eV of the low-temperature polymorph to 0.23 eV of the high
      temperature polymorph corresponding to a different occupancy causing a change in
      the number of the available charge carriers, explaining the change of
      conductivity by 2 orders of magnitude at the phase transition. These gap values
      are also consistent with structural, IR, electrical conductivity, and magnetic
      susceptibility data of Itkis et al. The proximity of the monomers in the stacking
      dimers is closely related to the spin crossover in this material.

PMID- 14583011
TI  - Water-protein interactions in microcrystalline crh measured by 1H-13C solid-state
      NMR spectroscopy.
AB  - Using solid-state NMR carbon-proton dipolar correlation spectroscopy, we observed
      hydrogen exchange on the millisecond time scale between water molecules and
      protein protons in a solid sample. These interactions are shown to be related to
      important structural features of the protein such as hydrogen-bonding or salt
      bridge networks.

PMID- 14583012
TI  - Protein alignment by a coexpressed lanthanide-binding tag for the measurement of
      residual dipolar couplings.
AB  - A protein fusion construct of human ubiquitin with an N-terminal lanthanide
      binding tag (LBT) enables observation of long-range orientational restraints in
      solution NMR from residual dipolar couplings (RDCs) due to paramagnetic alignment
      of the protein. The paramagnetic lanthanide ions Tb3+, Dy3+, and Tm3+ are shown
      to bind to the LBT and induce different alignment tensors, in agreement with
      theory. RDCs, measured relative to the diamagnetic Lu3+, range from -7.6 to 5.5
      Hz for Tb3+ and -6.6 to 6.1 Hz for Dy3+, while an opposite alignment tensor is
      observed for Tm3+ (4.5 to -2.9 Hz) at 800 MHz. Experimental RDCs are in excellent
      agreement with those predicted on the basis of the X-ray structure of the
      protein.

PMID- 14583013
TI  - A catalytic reaction of alkynes via multiple-site functionalization.
AB  - The first multiple-site activation of alkynes with amine/halogen functionalities
      has been established. The reaction was performed by treating alkyne with N,N
      dichlorobenzenesulfonamide at 80 degrees C in the presence of palladium acetate
      catalyst. A new mechanism was proposed which involves the novel formation of beta
      halovinyl palladium and pi-allylpalladium species. Excellent regio- and
      stereoselectivities were achieved with the absolute structure determined by X-ray
      structural analysis.

PMID- 14583014
TI  - Interaction between ketopantolactone and chirally modified Pt investigated by
      attenuated total reflection IR concentration modulation spectroscopy.
AB  - The combination of ATR-IR and modulation spectroscopy allowed for the study of
      the interaction of ketopantolactone with Pt/Al2O3 films chirally modified by
      cinchonidine under hydrogenation conditions. The spectra reveal a significant
      influence of ketopantolactone on the adsorption of the modifier and indicate a N
      H-O hydrogen bond between modifier and reactant. The latter was corroborated by a
      comparative study with N-methyl cinchonidine chloride modified Pt/Al2O3.

PMID- 14583015
TI  - Dioxygen activation by an osmium-dihydride: preparation and characterization of a
      d4 square-planar complex.
AB  - Exposure of OsH2Cl2(PiPr3)2 to air or bubbling with pure O2 affords the dioxo
      Os(VI) compound OsO2Cl2(PiPr3)2 as result of a direct O=O double bond activation
      reaction. This Os(VI) species is reduced in the presence of n-BuLi to the novel
      dioxo-Os(IV) derivative OsO2(PiPr3)2, a rare example of a d4 square-planar
      compound.

PMID- 14583016
TI  - Synthesis, structure, and thermolysis of a pentacoordinate 1,2-oxastibetane.
AB  - Isomeric pentacoordinate 1,2-oxastibetanes bearing the Martin ligand have been
      synthesized by the reactions of bromo(2-hydroxyalkyl)stiboranes with sodium
      hydride of which one of the isomers was characterized by X-ray crystallographic
      analysis and NMR spectroscopy. Thermolysis of the isomer shown (CD3CN, 140
      degrees C) afforded the oxirane with retention of configuration, while its
      thermolyses in the presence of lithium bromide and LiBPh4.3DME provided the
      oxirane with inversion of configuration and the olefin. The addition of the salts
      in the thermolyses of this pentacoordinate 1,2-oxastibetane controls both the
      stereochemistry of the oxirane formed and the ratios of the three main products.

PMID- 14583017
TI  - [Cr(N)Cl4]2-: a simple nitrido complex synthesized by nitrogen-atom transfer.
AB  - A new general route to nitrido complexes of Cr(V) based on nitrogen-atom transfer
      from Mn(N)(salen) to labile CrCl3(THF)3 is presented. By this approach, the
      simplest nitrido complex of a first row transition metal, [Cr(N)Cl4]2-, has been
      synthesized and isolated. [[N(CH3)4]2[Cr(N)Cl4].H2O crystallizes in the cubic
      space group Fm-3m with disordered anions. Cr-N is 1.555(19) A, Cr-Cl is
      2.2912(16) A, and N-Cr-Cl is 101.24(4) degrees . The orbital splitting scheme of
      [Cr(N)Cl4]2- is extreme with the dx2-y2 orbital 10 000 cm-1 lower in energy than
      the degenerate {dzx, dyz} set of orbitals destabilized by pi-bonding with the
      nitrido ligand. Hydrolysis of [Cr(N)Cl4]2 preserves the {CrN}2+ moiety.

PMID- 14583018
TI  - Group transfer from nickel imido, phosphinidene, and carbene complexes to
      ethylene with formation of aziridine, phosphirane, and cyclopropane products.
AB  - The reactions of nickel complexes bearing terminal imido, phosphinidene, and
      carbene ligands with ethylene are reported. In all three cases, corresponding
      three-membered rings, aziridine, phosphirane, and cyclopropane, were produced in
      moderate to excellent yields. NMR spectra of the phosphinidene (dtbpe)Ni=P(dmp)
      reaction with ethylene show a [2+2] cycloaddition adduct before phosphirane
      formation. A labeling study with trans-ethylene-d2 shows formation of aziridine
      and phosphirane proceeds with net retention of relative stereochemistry.

PMID- 14583019
TI  - Protein charge-state distributions in electrospray-ionization mass spectrometry
      do not appear to be limited by the surface tension of the solvent.
AB  - According to a current model for protein electrospray, the charge-state
      distributions (CSDs) observed by electrospray-ionization mass spectrometry (ESI
      MS) are controlled by the Rayleigh-limit charge of the droplets that generate the
      gas-phase protein ions. A testable prediction of this model is that the maximum
      charge state displayed by proteins in ESI-MS should respond to changes in the
      surface tension of the ESI droplets according to the Rayleigh equation. In this
      work, we subject this specific hypothesis to direct experimental testing. We show
      data obtained by time-of-flight (TOF) nano-ESI-MS with several different proteins
      in aqueous solutions containing 20-50% 1-propanol or 40% 1,2-propylene glycol.
      Both of these compounds have lower vapor pressure and lower surface tension than
      water. Propylene glycol also has a lower evaporation rate than water, providing
      an even more stringent test for surface tension effects in late ESI droplets.
      None of these cosolvents affects the CSDs of either folded or unfolded proteins
      as predicted by the Rayleigh-charge model. The only changes induced by 1-propanol
      can be ascribed to protein unfolding triggered above critical concentrations of
      the alcohol. Below such a threshold, no shift of the CSDs toward lower charge
      states is observed. The presence of 40% propylene glycol in the original protein
      solutions gives rise to CSDs that either are the same as those in the control
      samples or present much smaller changes than those calculated by the Rayleigh
      equation. Thus, the charge states of gas-phase protein ions produced by
      electrospray do not seem to be limited by the surface tension of the solvent.
      They rather appear to be quite protein-specific.

PMID- 14583020
TI  - Alumina nanotubes containing lithium of high ion mobility.
AB  - We revealed the first example of a crystalline lithium aluminate nanotube with
      thermal stability prepared by a surfactant-driven hydrothermal procedure. The
      obtained nanotube showed an interesting structure unknown thus far for oxide
      nanotubes such as cylindrical bundles of lithium aluminate subnanotubules. These
      novel nanotubules had walls of crystalline lithium aluminate with a honeycomblike
      Al-O wall-network surrounding a central lithium core that forms a linear array of
      atoms and could be a promising solid ion conducting material.

PMID- 14583021
TI  - Strong two-photon absorption of self-assembled butadiyne-linked bisporphyrin.
AB  - Two-photon absorption (2PA) properties of self-assembled porphyrins were
      investigated. The butadiyne-linked porphyrin array exhibited a 20 times larger
      2PA cross section than the meso-meso-linked self-assembled array due to the
      expansion of pi-conjugation. Higher-order nonlinear absorption was also observed
      in the former porphyrin.

PMID- 14583023
TI  - Chiroptical switching in a bistable molecular shuttle.
AB  - Although various methods for switching the positions of macrocycles in bistable
      rotaxane-based molecular shuttles have been developed, exploiting such movements
      to trigger property changes has thus far received little attention. Here we
      describe one of the first examples of a property change achieved through a
      controlled large-amplitude translational motion in a rotaxane; a novel type of
      chiroptical switch is described, in which light-induced translation of the
      macrocycle along the thread of a [2]rotaxane produces a strong induced circular
      dichroism (ICD) response only when the macrocycle is hydrogen-bonded to a chiral
      peptide station.

PMID- 14583022
TI  - A light-activated probe of intracellular protein kinase activity.
AB  - The first example of a photoactivated probe of intracellular enzymatic activity
      is described. The caged derivative of a fluorescent protein kinase C peptide
      based sensor was prepared by modifying the free hydroxyl group of a
      phosphorylatable serine moiety with a photolabile appendage that blocks
      phosphoryl transfer. We have demonstrated that the caged sensor allows one to (1)
      sample PKC activity with exquisite temporal precision, (2) control the relative
      amount of active sensor available for phosphorylation, and (3) examine protein
      kinase activity at multiple time points.

PMID- 14583024
TI  - Glycine on a wet pyrite surface at extreme conditions.
AB  - We present ab initio molecular dynamics (MD) simulations of the simplest amino
      acid, glycine, at the water/pyrite interface under extreme pressure/temperature
      conditions. These simulations are aimed to contribute to the discussion of the
      "iron-sulfur world" (ISW) scenario, an intriguing proposal in the controversial
      field of "Origin of Life" research. The simulations show that glycine easily
      desorbs from a water/pyrite interface through hydrogen-bond assistance. The
      retention time is only of the order of a picosecond, and the surface bonding is
      best understood as a relatively weak electrostatic interaction. However, we have
      found indications of glycine activation due to the interaction with the surface,
      and thus for a possible reaction with a suitable anchor molecule.

PMID- 14583025
TI  - Hollow nanostructures of platinum with controllable dimensions can be synthesized
      by templating against selenium nanowires and colloids.
AB  - Hollow nanostructures of platinum have been synthesized by reducing PtCl2 with
      alcohol in the presence of selenium nanowires or colloids. The Se template could
      be removed by soaking the resultant Se@Pt nanostructures in hydrazine or by
      heating them to 200-250 degrees C. The size and wall thickness of the
      polycrystalline hollow nanostructures could be controlled by varying the
      template, reaction time, and the concentration of PtCl2.

PMID- 14583026
TI  - Nanoporous materials with spherical and gyroid cavities created by quantitative
      etching of polydimethylsiloxane in polystyrene-polydimethylsiloxane block
      copolymers.
AB  - A new method for quantitative etching of the poly(dimethylsiloxane) block in
      polystyrene-poly(dimethylsiloxane) (PS-PDMS) block copolymers is reported.
      Reacting the block copolymer with anhydrous hydrogen fluoride renders a
      nanoporous material (NPM) with the remaining glassy PS maintaining the original
      bulk morphology. 1H NMR, mass difference, size exclusion chromatography, and X
      ray photoelectron spectroscopy were used to characterize the materials before and
      after etching. NPMs containing spherical and gyroid cavities were prepared, as
      ascertained by small-angle X-ray scattering. This is the first report on block
      copolymer-based NPM films of millimeter thickness containing secluded spherical
      holes. Surface images by AFM and SEM are consistent with the SAXS findings.

PMID- 14583027
TI  - Development of chiral nucleophilic pyridine catalysts: applications in asymmetric
      quaternary carbon synthesis.
AB  - TADMAP (1a), a new chiral DMAP catalyst, has been designed to place a C(3)
      benzylic trityl group over one face of the pyridine ring, while a C(3)-benzylic
      acetoxy group creates a chirotopic environment on the other face. TADMAP was
      prepared in four steps (37% overall) from triphenylacetic acid and
      (dimethylamino)pyridine and was resolved using camphorsulfonic acid. TADMAP
      catalyzes the enantioselective rearrangement from oxazolyl phenyl carbonates 4 to
      azlactones 5, from furanyl phenyl carbonate 8 to the furanone 9, from the
      benzofuranyl carbonates 11a and 11b to benzofuranones 12a and 12b, and from the
      indolyl carbonates 11c and 11d to oxindoles 12c and 12d. The products are formed
      in good yield and, in most cases, with practical levels of enantiomer excess at
      the newly formed quaternary carbon.

PMID- 14583028
TI  - Catalytic benzene alkylation over mesoporous zeolite single crystals: improving
      activity and selectivity with a new family of porous materials.
AB  - Mesoporous zeolite single-crystal catalysts are shown to be both more active and
      more selective than conventional zeolite catalysts in the alkylation of benzene
      with ethene. The superior catalytic properties are ascribed to improved mass
      transport in the mesoporous zeolite crystals. Thus, mesoporous zeolite single
      crystal catalysts combine the high acidity, shape-selectivity, and hydrothermal
      stability of zeolites with the efficient mass transport that is typically
      achieved in mesoporous materials.

PMID- 14583029
TI  - Evidence for environmentally coupled hydrogen tunneling during dihydrofolate
      reductase catalysis.
AB  - Hydride transfer during catalysis by dihydrofolate reductase from Thermotoga
      maritima has been studied by stopped flow spectroscopy. The reduction of
      dihydrofolate by NADPH showed a biphasic temperature dependence of the deuterium
      kinetic isotope effect. At temperatures above 25 degrees C the KIE was
      temperature independent, while the reaction rates were strongly temperature
      dependent. Below 25 degrees C the KIE becomes dependent on temperature, and the
      ratio of the preexponential factors is inverse, suggesting a greater role for
      active dynamics that modulate the tunneling distance.

PMID- 14583030
TI  - MAS NMR structure of a microcrystalline Cd-bacteriochlorophyll d analogue.
AB  - Solid-state NMR is an emerging method to obtain structural information in
      molecular biology and nanotechnology for systems that are inaccessible to
      solution NMR or diffraction methods. While solution NMR generally converges upon
      families of structures in a bottom-up approach, solid NMR structure determination
      will have to take into account the top-down constraints that follow from the
      additional requirement that the entire 3D space must be packed in an orderly
      fashion. We used MAS NMR together with molecular modeling calculations in steps
      to establish a detailed model of the local crystal structure of an aggregate of
      uniformly 13C- and 15N-labeled Cd-chlorophyllide d, a model for the chlorosomal
      antennae. In this way we converge upon a space group P21 with a = 14.3 A, b =
      27.3 A, c = 6.4 A, beta = 147.2 degrees and Z = 2.

PMID- 14583031
TI  - Tandem lesions are the major products resulting from a pyrimidine nucleobase
      radical.
AB  - Nucleobase radicals (e.g., 1) are the major family of reactive intermediates
      formed when DNA is exposed to gamma-radiolysis. Independent generation of 1 in
      chemically synthesized oligonucleotides reveals that formation of this nucleobase
      radical under aerobic conditions results in the formation of tandem lesions
      approximately 65% of the time. The distribution of lesions formed with the 5'-
      and 3'-adjacent nucleotides is dependent upon the secondary structure of duplex
      DNA. Tandem lesions, which are defined as two contiguously, damaged nucleotides
      in a single DNA strand, are of significant biological interest. The yield of
      tandem lesions from 1 is much greater than was previously believed. The
      observations presented could have significant ramifications on how scientists
      interpret the effects of gamma-radiolysis on DNA.

PMID- 14583032
TI  - Catalytic mechanism of S-ribosylhomocysteinase (LuxS): direct observation of
      ketone intermediates by 13C NMR spectroscopy.
AB  - S-Ribosylhomocysteinase (LuxS) catalyzes the cleavage of the thioether linkage of
      S-ribosylhomocysteine (SRH) to produce l-homocysteine and 4,5-dihydroxy-2,3
      pentanedione (DHPD). This is a key step in the biosynthetic pathway of the type
      II autoinducer (AI-2) in both Gram-positive and Gram-negative bacteria. Previous
      studies demonstrated that LuxS contains a catalytically essential Fe2+ ion. The
      catalytic mechanism of LuxS was investigated using 2- and 3-13C-labeled SRH as
      substrate and 13C NMR spectroscopy. These studies revealed the presence of 2- and
      3-keto intermediates in the catalytic pathway. The 2-keto intermediate was
      chemically synthesized, and its chemical and kinetic competence was demonstrated.
      The results support a catalytic mechanism in which the metal ion catalyzes an
      internal redox reaction, shifting the carbonyl group from the C-1 position to the
      C-3 position. Subsequent beta-elimination at the C-4 and C-5 positions releases
      homocysteine as a free thiol. The results also suggest that Cys-84 and Glu-57 are
      the possible general acids/bases for proton transfer during catalysis and that
      the keto intermediates are released from the enzyme active site before rebinding
      and completion of the reaction.

PMID- 14583033
TI  - Manadomanzamines A and B: a novel alkaloid ring system with potent activity
      against mycobacteria and HIV-1.
AB  - Two novel alkaloids, named manadomanzamines A (1) and B (2), were isolated from
      an Indonesian sponge Acanthostrongylophora sp. (Haplosclerida: Petrosiidae).
      Their structures were elucidated and shown to be a novel organic skeleton related
      to the manzamine type alkaloids. Their absolute configuration and conformation
      were determined by CD, NOESY, and molecular modeling analysis. The microbial
      community analysis for the sponge that produces these unprecedented alkaloids has
      also been completed. Manadomanzamines A (1) and B (2) exhibited strong activity
      against Mycobacterium tuberculosis (Mtb) with MIC values of 1.9 and 1.5 mug/mL,
      respectively. Manadomanzamines A and B also exhibit activities against human
      immunodeficiency virus (HIV-1) and AIDS opportunistic fungal infections.

PMID- 14583034
TI  - Reversible "irreversible" inhibition of chymotrypsin using nanoparticle
      receptors.
AB  - Anionically functionalized amphiphilic nanoparticles efficiently inhibit
      chymotrypsin through electrostatic binding followed by protein denaturation. We
      demonstrate the ability to disrupt this "irreversible" inhibition of chymotrypsin
      through modification of the nanoparticle surface using cationic surfactants. Up
      to 50% of original chymotrypsin activity is rescued upon long-chain surfactant
      addition. Dynamic light-scattering studies demonstrate that chymotrypsin is
      released from the nanoparticle surface. The conformation of the rescued
      chymotrypsin was characterized by fluorescence and fluorescence anisotropy,
      indicating that chymotrypsin regains a high degree of native structure upon
      surfactant addition.

PMID- 14583035
TI  - Solution 1H, 15N NMR spectroscopic characterization of substrate-bound, cyanide
      inhibited human heme oxygenase: water occupation of the distal cavity.
AB  - A solution NMR spectroscopic study of the cyanide-inhibited, substrate-bound
      complex of uniformly (15)N-labeled human heme oxygenase, hHO, has led to
      characterization of the active site with respect to the nature and identity of
      strong hydrogen bonds and the occupation of ordered water molecules within both
      the hydrogen bonding network and an aromatic cluster on the distal side. [(1)H
      (15)N]-HSQC spectra confirm the functionalities of several key donors in
      particularly robust H-bonds, and [(1)H-(15)N]HSQC-NOESY spectra lead to the
      identification of three additional robust H-bonds, as well as the detection of
      two more relatively strong H-bonds whose identities could not be established. The
      3D NMR experiments provided only a modest, but important, extension of
      assignments because of the loss of key TOCSY cross-peaks due to the line
      broadening from a dynamic heterogeneity in the active site. Steady-state NOEs
      upon saturating the water signal locate nine ordered water molecules in the
      immediate vicinity of the H-bond donors, six of which are readily identified in
      the crystal structure. The additional three are positioned in available spaces to
      account for the observed NOEs. (15)N-filtered steady-state NOEs upon saturating
      the water resonances and (15)N-filtered NOESY spectra demonstrate significant
      negative NOEs between water molecules and the protons of five aromatic rings.
      Many of the NOEs can be rationalized by water molecules located in the crystal
      structure, but strong water NOEs, particularly to the rings of Phe47 and Trp96,
      demand the presence of at least an additional two immobilized water molecules
      near these rings. The H-bond network appears to function to order water molecules
      to provide stabilization for the hydroperoxy intermediate and to serve as a
      conduit to the active site for the nine protons required per HO turnover.

PMID- 14583036
TI  - Synthesis and characterization of potent bivalent amyloidosis inhibitors that
      bind prior to transthyretin tetramerization.
AB  - The misfolding of transthyretin (TTR), including rate-limiting tetramer
      dissociation and partial monomer denaturation, is sufficient for TTR misassembly
      into amyloid and other abnormal quaternary structures associated with senile
      systemic amyloidosis, familial amyloid polyneuropathy, and familial amyloid
      cardiomyopathy. Monovalent small molecules that bind to one or both of the
      unoccupied thyroid hormone binding sites at the TTR quaternary structure
      interface stabilize the native state, raising the kinetic barrier for tetramer
      dissociation sufficiently that the rate of dissociation, and therefore
      amyloidosis, becomes slow. Bivalent amyloid inhibitors that bind to both binding
      sites simultaneously are reported herein. The candidate bivalent inhibitors are
      generally unable to bind to the native TTR tetramer and typically do not engage
      in monovalent binding owing to a strong inhibitor orientation preference.
      However, the TTR quaternary structure can assemble around several of the bivalent
      inhibitors if the inhibitor intercepts the protein before assembly occurs. Some
      of the wild-type TTR.bivalent inhibitor complexes prepared in this fashion retain
      a tetrameric structure when subjected to substantial denaturation stresses (8 M
      urea, 120 h). The best bivalent inhibitor reduced acid-mediated TTR (3.6 microM)
      amyloid fibril formation to 6% of that exhibited by TTR in the absence of
      inhibitor, a significant improvement over the approximately 30% observed for the
      best monovalent inhibitors (3.6 microM, 72 h). The apparent dissociation rate of
      the best bivalent inhibitor is effectively zero, consistent with the idea that
      TTR tetramer dissociation and inhibitor dissociation are linked-as a result of
      the inhibitor-templating tetramer assembly. X-ray cocrystal structures of two of
      the complexes demonstrate that the bivalent inhibitors simultaneously occupy both
      sites in TTR, consistent with the 1:1 binding stoichiometry derived from HPLC
      analysis. The purpose of this study was to demonstrate that bivalent inhibitors
      could be useful; what resulted are the best inhibitors produced to date. In this
      context, molecules capable of intercepting TTR during folding and assembly in the
      lumen of the endoplasmic reticulum would be of obvious interest.

PMID- 14583037
TI  - SUBPOL: a novel SUcrose-Based Polymer support for solid-phase peptide synthesis
      and affinity chromatography applications.
AB  - A novel SUcrose-Based Polymer support (SUBPOL) with tailored morphology suitable
      for the use in solid-phase peptide synthesis (SPPS) is described, and its
      application as a hydrophilic affinity matrix for the specific removal of
      fibrinogen from human plasma is demonstrated. After suspension polymerization of
      partly methacrylated 2,1':4,6-di-O-isopropylidene sucrose and subsequent removal
      of the protecting groups, hydrophilic spherical polymer beads were obtained. The
      morphology of the resulting resin was controlled by variation of the porogen as
      well as the average degree of substitution with respect to the methacryloyl
      groups of the monomer mixture. After introduction of amino groups for a permanent
      attachment of immobilized peptide ligands, prevention of unintended
      esterification during SPPS was achieved by silylation of remaining hydroxy
      groups. Alternatively, a Rink amide linker was introduced prior to SPPS to allow
      cleavage and subsequent analysis of the peptide assembled on the SUBPOL resins.
      Two hexapeptides of sequence kwiivw and hffflw, consisting of d-amino acids, as
      well as a 19-mer peptide corresponding to the sequence GSGVRGDFGSLAPRVARQL of the
      VP1 protein from the foot-and-mouse disease virus (FMDV) were successfully
      prepared both manually or in a semi-automated process on SUBPOL resins according
      to the Fmoc/tBu strategy. Yields and purities were comparable to peptides
      prepared on commercially available polystyrene resins. A specific affinity
      adsorbent containing the fibrinogen-binding pentapeptide GPRPK was prepared by
      SPPS on SUBPOL resins of different morphology, and the strong impact of the
      affinity matrix on adsorption performance was demonstrated.

PMID- 14583038
TI  - Solid-phase oligodeoxynucleotide synthesis: a two-step cycle using peroxy anion
      deprotection.
AB  - A novel solid-phase phosphoramidite based oligodeoxynucleotide two-step synthesis
      method has been developed. Keys to this method are replacement of the 5'
      dimethoxytrityl blocking group with an aryloxycarbonyl and the use of N
      dimethoxytrityl protection for the exocyclic amines of adenine and cytosine. With
      these modifications, coupling of each 2'-deoxynucleoside 3'-phosphoramidite to
      the growing oligodeoxynucleotide on the solid support can be followed by
      treatment with an aqueous mixture of peroxy anions buffered at pH 9.6. This
      reagent effectively removes the carbonate protecting group and simultaneously
      oxidizes the phosphite internucleotide linkage. As a consequence a new two-step
      synthesis cycle is possible. Oligodeoxynucleotides synthesized using this
      approach are identical to authentic samples when tested by a variety of
      analytical techniques.

PMID- 14583039
TI  - Regio- and enantioselective alkane hydroxylation with engineered cytochromes P450
      BM-3.
AB  - Cytochrome P450 BM-3 from Bacillus megaterium was engineered using a combination
      of directed evolution and site-directed mutagenesis to hydroxylate linear alkanes
      regio- and enantioselectively using atmospheric dioxygen as an oxidant. BM-3
      variant 9-10A-A328V hydroxylates octane at the 2-position to form S-2-octanol
      (40% ee). Another variant, 1-12G, also hydroxylates alkanes larger than hexane
      primarily at the 2-position but forms R-2-alcohols (40-55% ee). These
      biocatalysts are highly active (rates up to 400 min(-1)) and support thousands of
      product turnovers. The regio- and enantioselectivities are retained in whole-cell
      biotransformations with Escherichia coli, where the engineered P450s can be
      expressed at high levels and the cofactor is supplied endogenously.

PMID- 14583040
TI  - Using DNA-binding proteins as an analytical tool.
AB  - We propose that DNA-binding proteins can be used as highly efficient and
      versatile tools in analyses of DNA, RNA, and proteins. This work reports assays
      applying specific affinity probes: hybridization probes for analyses of DNA and
      RNA, and aptamer probes for analyses of proteins. Both types of probes are single
      stranded DNA. In affinity analyses, in general, the probe (P) binds to a target
      molecule (T), and the amounts of the probe-target complex (P.T) and unbound P are
      determined. Distinguishing between P and P.T can be achieved by electrophoretic
      separation. If the electrophoretic mobilities of P and P.T are close in gel-free
      media, which is always the case for hybridization analyses, separation typically
      requires the use of a sieving matrix. Here we utilized a single-stranded DNA
      binding protein (SSB) to facilitate highly efficient gel-free separation of P and
      P.T in capillary electrophoresis (CE) for three types of targets: DNA, RNA, and
      proteins. When present in the CE run buffer, SSB binds differently to P and P.T.
      Due to this selective binding, SSB induces difference in electrophoretic
      mobilities of P and P.T in an SSB concentration-dependent fashion. The difference
      in the electrophoretic mobilities allows for affinity analyses of DNA, RNA, and
      proteins in gel-free CE. The large number of well-characterized DNA- and RNA
      binding proteins and the diversity of their properties will allow researchers to
      design a comprehensive tool set for quantitative analyses of DNA, RNA, and
      proteins. Such analyses will facilitate identification of genomic DNA in ultra
      small samples without error-prone and time-consuming PCR. They can also be used
      for monitoring gene expression at both mRNA and protein levels.

PMID- 14583041
TI  - Diselenides and allyl selenides as glutathione peroxidase mimetics. Remarkable
      activity of cyclic seleninates produced in situ by the oxidation of allyl omega
      hydroxyalkyl selenides.
AB  - A series of aliphatic diselenides and selenides containing coordinating
      substituents was tested for glutathione peroxidase (GPx)-like catalytic activity
      in a model system in which the reduction of tert-butyl hydroperoxide with benzyl
      thiol to afford dibenzyl disulfide and tert-butyl alcohol was performed under
      standard conditions and monitored by HPLC. Although the diselenides showed
      generally poor catalytic activity, allyl selenides proved more effective. In
      particular, allyl 3-hydroxypropyl selenide (25) rapidly generated 1,2
      oxaselenolane Se-oxide (31) in situ by a series of oxidation and [2,3]sigmatropic
      rearrangement steps. The remarkably active cyclic seleninate 31 proved to be the
      true catalyst, reacting with the thiol via a postulated mechanism in which the
      thioseleninate 32 is first produced, followed by further thiolysis to selenenic
      acid 33 and oxidation-dehydration to regenerate 31. In contrast to catalysis with
      GPx, formation of the corresponding selenenyl sulfide 34 comprises a competing
      deactivation pathway in the catalytic cycle of 31, as a separate experiment
      revealed that authentic 34 was a much less effective catalyst than 31. 1,2
      Oxaselenane Se-oxide (37), the six-membered homologue of 31, was formed similarly
      from allyl 4-hydroxybutyl selenide (26), but proved a less effective catalyst
      than 31. Compounds 31 and 37 are the first examples of unsubstituted monocyclic
      seleninate esters.

PMID- 14583042
TI  - Comparison of excited-state energy transfer in arrays of hydroporphyrins
      (chlorins, oxochlorins) versus porphyrins: rates, mechanisms, and design
      criteria.
AB  - A set of chlorin-chlorin and oxochlorin-oxochlorin dyads has been prepared with
      components in the same or different metalation states. In each case a 4,4'
      diphenylethyne linker spans the respective 10-position of each macrocycle. The
      dyads have been studied using static and time-resolved absorption and emission
      spectroscopy, resonance Raman spectroscopy, and electrochemical techniques.
      Excited-state energy transfer from a zinc chlorin to a free-base (Fb) chlorin
      occurs with a rate constant of (110 ps)(-1) and an efficiency of 93%; similar
      values of (140 ps)(-1) and 83% are found for the corresponding oxochlorin dyad.
      Energy transfer in both dyads is slower and less efficient than found previously
      for the analogous porphyrin dyad, which displays a rate of (24 ps)(-1) and a
      yield of 99%. The slower rates and diminished efficiencies in the ZnFb chlorin
      and oxochlorin dyads versus the ZnFb porphyrin dyad are attributed to
      substantially weaker linker-mediated through-bond (TB) electron-exchange coupling
      (as indicated by resonance Raman data). Although the through-space (TS, i.e.,
      dipole-dipole) coupling in the ZnFb-chlorin and -oxochlorin dyads is enhanced
      relative to the ZnFb porphyrin dyad (as indicated by Forster calculations), this
      enhancement is insufficient to compensate for the greatly diminished TB coupling.
      Taken together, the chlorin and oxochlorin dyads examined herein serve as
      benchmarks for elucidating the energy-transfer, electrochemical, and other
      properties of light-harvesting arrays containing multiple chlorins or
      oxochlorins.

PMID- 14583043
TI  - Spectroscopic consequences of a mixed valence excited state: quantitative
      treatment of a dihydrazine diradical dication.
AB  - A model for the quantitative treatment of molecular systems possessing mixed
      valence excited states is introduced and used to explain observed spectroscopic
      consequences. The specific example studied in this paper is 1,4-bis(2-tert-butyl
      2,3-diazabicyclo[2.2.2]oct-3-yl)-2,3,5,6-tetramethylbenzene-1,4-diyl dication.
      The lowest energy excited state of this molecule arises from a transition from
      the ground state where one positive charge is associated with each of the
      hydrazine units, to an excited state where both charges are associated with one
      of the hydrazine units, that is, a Hy-to-Hy charge transfer. The resulting
      excited state is a Class II mixed valence molecule. The electronic emission and
      absorption spectra, and resonance Raman spectra, of this molecule are reported.
      The lowest energy absorption band is asymmetric with a weak low-energy shoulder
      and an intense higher energy peak. Emission is observed at low temperature. The
      details of the absorption and emission spectra are calculated for the coupled
      surfaces by using the time-dependent theory of spectroscopy. The calculations are
      carried out in the diabatic basis, but the nuclear kinetic energy is explicitly
      included and the calculations are exact quantum calculations of the model
      Hamiltonian. Because the transition involves the transfer of an electron from the
      hydrazine on one side of the molecule to the hydrazine on the other side and vice
      versa, the two transitions are antiparallel and the transition dipole moments
      have opposite signs. Upon transformation to the adiabatic basis, the dipole
      moment for the transition to the highest energy adiabatic surface is nonzero, but
      that for the transition to the lowest surface changes sign at the origin. The
      energy separation between the two components of the absorption spectrum is twice
      the coupling between the diabatic basis states. The bandwidths of the electronic
      spectra are caused by progressions in totally symmetric modes as well as
      progressions in the modes along the coupled coordinate. The totally symmetric
      modes are modeled as displaced harmonic oscillators; the frequencies and
      displacements are determined from resonance Raman spectra. The absorption,
      emission, and Raman spectra are fit simultaneously with one parameter set. The
      coupling in the excited electronic state H(ab)(ex) is 2000 cm(-1). Excited-state
      mixed valence is expected to be an important contributor to the electronic
      spectra of many organic and inorganic compounds. The energy separations and
      relative intensities enable the excited-state properties to be calculated as
      shown in this paper, and the spectra provide new information for probing and
      understanding coupling in mixed valence systems.

PMID- 14583044
TI  - Cascade cyclizations and couplings involving nickel enolates.
AB  - A new strategy for effecting cascade cyclization processes using nickel enolates
      has been developed. Nickel enolates may be cleanly generated by the oxidative
      cyclization of an enal and alkyne with Ni(0), and the resulting enolate may be
      functionalized by a variety of alkylation processes. Partially and fully
      intramolecular versions of the process allow the rapid synthesis of complex
      polycyclics from simple achiral, acyclic precursors.

PMID- 14583045
TI  - First enantiospecific total synthesis of the antitubercular marine natural
      product pseudopteroxazole. Revision of assigned stereochemistry.
AB  - A concise, enantiospecific synthesis of pseudopteroxazole (3), which had
      originally been assigned structure 1, has been accomplished starting from S-(-)
      limonene. The known cyclohexanone 5 was converted in five steps to the alpha,beta
      enone 8 by a modified Robinson annulation. Transformation of 8 to the
      orthogonally protected amino phenol 11 was accomplished by a new modification of
      the Wolff-Semmler rearrangement. The synthesis was completed by cationic
      cyclization to form 14 diastereoselectively and subsequent introduction of the
      terminal oxazole subunit.

PMID- 14583046
TI  - Mechanism of asymmetric hydrogenation of ketones catalyzed by BINAP/1,2-diamine
      rutheniumII complexes.
AB  - Asymmetric hydrogenation of acetophenone with trans-RuH(eta(1)-BH(4))[(S)
      tolbinap][(S,S)-dpen] (TolBINAP = 2,2'-bis(di-4-tolylphosphino)-1,1'-binaphthyl;
      DPEN = 1,2-diphenylethylenediamine) in 2-propanol gives (R)-phenylethanol in 82%
      ee. The reaction proceeds smoothly even at an atmospheric pressure of H(2) at
      room temperature and is further accelerated by addition of an alkaline base or a
      strong organic base. Most importantly, the hydrogenation rate is initially
      increased to a great extent with an increase in base molarity but subsequently
      decreases. Without a base, the rate is independent of H(2) pressure in the range
      of 1-16 atm, while in the presence of a base, the reaction is accelerated with
      increasing H(2) pressure. The extent of enantioselection is unaffected by
      hydrogen pressure, the presence or absence of base, the kind of base and
      coexisting metallic or organic cations, the nature of the solvent, or the
      substrate concentrations. The reaction with H(2)/(CH(3))(2)CHOH proceeds 50 times
      faster than that with D(2)/(CD(3))(2)CDOD in the absence of base, but the rate
      differs only by a factor of 2 in the presence of KO-t-C(4)H(9). These findings
      indicate that dual mechanisms are in operation, both of which are dependent on
      reaction conditions and involve heterolytic cleavage of H(2) to form a common
      reactive intermediate. The key [RuH(diphosphine)(diamine)](+) and its solvate
      complex have been detected by ESI-TOFMS and NMR spectroscopy. The hydrogenation
      of ketones is proposed to occur via a nonclassical metal-ligand bifunctional
      mechanism involving a chiral RuH(2)(diphosphine)(diamine), where a hydride on Ru
      and a proton of the NH(2) ligand are simultaneously transferred to the C=O
      function via a six-membered pericyclic transition state. The NH(2) unit in the
      diamine ligand plays a pivotal role in the catalysis. The reaction occurs in the
      outer coordination sphere of the 18e RuH(2) complex without C=O/metal
      interaction. The enantiofaces of prochiral aromatic ketones are kinetically
      differentiated on the molecular surface of the coordinatively saturated chiral
      RuH(2) intermediate rather than in a coordinatively unsaturated Ru template.

PMID- 14583047
TI  - Molecular imprinting inside dendrimers.
AB  - Synthetic hosts capable of binding porphyrins have been produced by a mixed
      covalent-noncovalent imprinting process wherein a single binding site is created
      within cross-linked dendrimers. Two synthetic hosts were prepared, using as
      templates 5,10,15,20-tetrakis(4-hydroxyphenyl)porphyrin and 5,10,15,20
      tetrakis(3,5-dihydroxyphenyl)porphyrin. These two templates were esterified with,
      respectively, fourth- and third-generation Frechet-type dendrons containing
      homoallyl end-groups. The resulting tetra- and octadendron macromolecules
      underwent the ring-closing metathesis reaction using Grubbs' Type I catalyst,
      RuCl(2)(P(C(6)H(5))(3))(2)(CHCH(2)C(6)H(5)), to give extensive interdendron cross
      linking. Hydrolytic removal of the porphyrin cores afforded imprinted hosts whose
      ability to bind porphyrins with various peripheral substituents was investigated
      by UV-visible spectrophotometric titrations and size exclusion chromatography.
      The results indicate a high yield of imprinted sites that show high selectivity
      for binding of porphyrins capable of making at least four hydrogen bonds, but
      only a moderate degree of shape selectivity.

PMID- 14583048
TI  - 8-Methylguanosine: a powerful Z-DNA stabilizer.
AB  - Various modified guanine derivatives were synthesized and introduced into G(4) of
      d(CGCGCG)(2) to evaluate their capacity to stabilize Z-form DNA. It was found
      that the incorporation of 8-methylguanosine (m(8)rG) in oligonucleotides
      stabilizes the Z form more dramatically than does the incorporation of 8-methyl
      2'-deoxyguanosine (m(8)G). This enhancement is ascribed to a reduction in the
      entropic penalty, which arises from the introduction of hydrophilic groups in
      solvent-exposed regions. The incorporation of m(8)rG into DNA sequences markedly
      stabilizes the Z form even in the absence of NaCl. The Z-DNA stabilizer allows
      oligonucleotides with a wide range of sequences to be converted to the Z form. It
      could be a powerful tool for examining the molecular basis of many types of Z
      form-specific reactions at the molecular level under physiological salt
      conditions.

PMID- 14583050
TI  - A cycloaddition cascade approach to the total synthesis of (-)-FR182877.
AB  - An asymmetric synthesis of the cytotoxic natural product, (-)-FR182877 (1), has
      been achieved. Chirality for the entire structure was established using two (4R)
      4-benzyl-2-oxazolidinone-mediated boron aldol reactions. A 19-membered
      macrocarbocycle was synthesized by the coupling of two fragments using a
      regioselective Suzuki coupling (17 + 23 --> 26; 84%) and macrocyclization of a
      beta-keto ester (30 --> 31; 77%). Oxidation of 31 triggered a sequence of
      stereoselective transannular Diels-Alder reactions (32 -->34; 63%) forming four
      new rings and seven new stereocenters in the pivotal construction event. This
      pentacyclic intermediate was subsequently transformed to (-)-FR182877.
      Semiempirical calculations of the transannular Diels-Alder cycloaddition cascade
      were carried out to determine the origins of asymmetric induction.

PMID- 14583049
TI  - Structural and spectroscopic studies of peptoid oligomers with alpha-chiral
      aliphatic side chains.
AB  - Substantial progress has been made in the synthesis and characterization of
      various oligomeric molecules capable of autonomous folding to well-defined,
      repetitive secondary structures. It is now possible to investigate sequence
      structure relationships and the driving forces for folding in these systems.
      Here, we present detailed analysis by X-ray crystallography, NMR, and circular
      dichroism (CD) of the helical structures formed by N-substituted glycine (or
      "peptoid") oligomers with alpha-chiral, aliphatic side chains. The X-ray crystal
      structure of a N-(1-cyclohexylethyl)glycine pentamer, the first reported for any
      peptoid, shows a helix with cis-amide bonds, approximately 3 residues per turn,
      and a pitch of approximately 6.7 A. The backbone dihedral angles of this pentamer
      are similar to those of a polyproline type I peptide helix, in agreement with
      prior modeling predictions. This crystal structure likely represents the major
      solution conformers, since the CD spectra of analogous peptoid hexamers,
      dodecamers, and pentadecamers, composed entirely of either (S)-N-(1
      cyclohexylethyl)glycine or (S)-N-(sec-butyl)glycine monomers, also have features
      similar to those of the polyproline type I helix. Furthermore, this crystal
      structure is similar to a solution NMR structure previously described for a
      peptoid pentamer comprised of chiral, aromatic side chains, which suggests that
      peptoids containing either aromatic or aliphatic alpha-chiral side chains adopt
      fundamentally similar helical structures in solution, despite distinct CD
      spectra. The elucidation of detailed structural information for peptoid helices
      with alpha-chiral aliphatic side chains will facilitate the mimicry of
      biomolecules, such as transmembrane protein domains, in a distinctly stable form.

PMID- 14583052
TI  - New n-type organic semiconductors: synthesis, single crystal structures, cyclic
      voltammetry, photophysics, electron transport, and electroluminescence of a
      series of diphenylanthrazolines.
AB  - The synthesis, properties, and electroluminescent device applications of a series
      of five new diphenylanthrazoline molecules 1a-1e are reported. Compounds 1b, 1c,
      and 1d crystallized in the monoclinic system with the space groups P2(1)/c, C2/c,
      and P2(1)/c, respectively, revealing highly planar molecules.
      Diphenylanthrazolines 1a-1e have a formal reduction potential in the range -1.39
      to -1.58 V (versus SCE) and estimated electron affinities (LUMO levels) of 2.90
      3.10 eV. Compounds 1a-1e emit blue light with fluorescence quantum yields of 58
      76% in dilute solution, whereas they emit yellow-green light as thin films. The
      diphenylanthrazoline molecules as the emissive layers in light-emitting diodes
      gave yellow light with a maximum brightness of 133 cd/m(2) and an external
      quantum efficiency of up to 0.07% in ambient air. Bilayer light-emitting diodes
      using compounds 1a-1e as the electron-transport layer and poly(2-methoxy-5-(2'
      ethyl-hexyloxy)-1,4-phenylene vinylene) as the emissive layer had a maximum
      external efficiency of 3.1% and 2.0 lm/W and a brightness of up to 965 cd/m(2) in
      ambient air. These results represent enhancements of up to 50 times in external
      quantum efficiency and 17 times in brightness when using 1a-1e as the electron
      transport materials in polymer light-emitting diodes. These results demonstrate
      that the new diphenylanthrazolines are promising n-type semiconductors for
      organic electronics.

PMID- 14583051
TI  - Real-time multicolor DNA detection with chemoresponsive diffraction gratings and
      nanoparticle probes.
AB  - We report a real-time DNA detection method that utilizes single-strand DNA
      modified nanoparticle probes and micropatterned chemoresponsive diffraction
      gratings interrogated simultaneously at multiple laser wavelengths. The surface
      bound nanoparticle probe based assay with the chemoresponsive diffraction grating
      signal transduction scheme results in an experimentally simple DNA detection
      protocol, displaying attributes of both detection methodologies: the high
      sensitivity and selectivity afforded by nanoparticle probes and the experimental
      simplicity, wavelength-dependent resonant enhancement features, and
      miniaturization potential provided by the diffraction-based sensing technology.

PMID- 14583053
TI  - Alloyed Zn(x)Cd(1-x)S nanocrystals with highly narrow luminescence spectral
      width.
AB  - High-quality alloyed Zn(x)Cd(1-x)S nanocrystals have been synthesized at high
      temperature by the reaction of a mixture of CdO- and ZnO-oleic acid complexes
      with sulfur in the noncoordinating solvent octadecene system. A series of
      monodisperse wurtzite Zn(x)Cd(1-x)S (x = 0.10, 0.25, 0.36, 0.53) nanocrystals
      were obtained with corresponding particle radii of 4.0, 3.2, 2.9, and 2.4 nm,
      respectively. With the increase of the Zn content, their photoluminescence (PL)
      spectra blue-shift systematically across the visible spectrum from 474 to 391 nm,
      indicating the formation of the alloyed nanocrystals. The alloy structure is also
      supported by the characteristic X-ray diffraction (XRD) patterns of these
      nanoalloys with different Zn mole fractions, in which their diffraction peaks
      systematically shift to larger angles as the Zn content increases. The lattice
      parameter c measured from XRD patterns decreases linearly with the increase of Zn
      content. This trend is consistent with Vegard's law, which further confirms the
      formation of homogeneous nanoalloys. These monodisperse wurtzite Zn(x)Cd(1-x)S
      nanoalloys possess superior optical properties with PL quantum yields of 25-50%,
      especially the extremely narrow room-temperature emission spectral width (full
      width at half-maximum, fwhm) of 14-18 nm. The obtained narrow spectral width
      stems from the uniform size and shape distribution, the high composition
      homogeneity, and the relatively large particle radius, which is close to or
      somewhat larger than the exciton Bohr radius. The process by which the initial
      structure with random spatial composition fluctuations turns into an alloy (solid
      solution) with homogeneous composition is clearly demonstrated by the temporal
      evolution of the PL spectra during the annealing progress.

PMID- 14583054
TI  - Modifying electronic communication in dimolybdenum units by linkage isomers of
      bridged oxamidate dianions.
AB  - Reactions of Mo(2)(O(2)CCH(3))(DAniF)(3), DAniF = N,N'-di-p-anisylformamidinate,
      with oxamidate dianions [ArNC(O)C(O)NAr](2-), Ar = C(6)H(5) and p-anisyl, give
      pairs of isomeric compounds where the [Mo(2)] units are bridged by the oxamidate
      anions. For the alpha isomers, the C-C unit of the dianion is nearly
      perpendicular to the Mo-Mo bonds, and these are essentially perpendicular to each
      other. For the beta isomers, the corresponding C-C unit and the Mo-Mo bonds are
      essentially parallel to each other. Each type of isomer is stable in solution.
      The electronic communication as measured by the DeltaE(1/2) for the oxidation of
      each of the Mo(2) units is significantly better for the beta isomers. This is
      supported also by the appearance of what is conventionally called an intervalence
      charge-transfer band in the near infrared region upon oxidation of the beta
      isomers but not the alpha isomers. Molecular mechanics and DFT calculations help
      explain the relative conformations in the alpha isomers and the relative energy
      differences between the alpha and beta isomers.

PMID- 14583055
TI  - Binding energies of water to sodiated valine and structural isomers in the gas
      phase: the effect of proton affinity on zwitterion stability.
AB  - The structures of valine (Val) and methylaminoisobutyric acid (Maiba) bound to a
      sodium ion, both with and without a water molecule, are investigated using both
      theory and experiment. Calculations indicate that, without water, sodiated Val
      forms a charge-solvated structure in which the sodium ion coordinates to the
      nitrogen and the carbonyl oxygen (NO-coordination), whereas Maiba forms a salt
      bridge structure in which the sodium ion coordinates to both carboxylate oxygens
      (OO-coordination). The addition of a single water molecule does not significantly
      affect the relative energies or structures of the charge-solvated and salt-bridge
      forms of either cluster, although in Maiba the mode of sodium ion binding is
      changed slightly by the water molecule. The preference of Maiba to adopt a
      zwitterionic form in these complexes is consistent with its higher proton
      affinity. Experimentally, the rates of water evaporation from clusters of
      Val.Na(+)(H(2)O) and Maiba.Na(+)(H(2)O) are measured using blackbody infrared
      radiative dissociation (BIRD). The dissociation rates from the Val and Maiba
      complexes are compared to water evaporation rates from model complexes of known
      structure over a wide range of temperatures. Master equation modeling of the BIRD
      kinetic data yields a threshold dissociation energy for the loss of water from
      sodiated valine of 15.9 +/- 0.2 kcal/mol and an energy of 15.1 +/- 0.3 kcal/mol
      for the loss of water from sodiated Maiba. The threshold dissociation energy of
      water for Val.Na(+)(H(2)O) is the same as that for the charge-solvated model
      isomers, while the salt-bridge model complex has the same water threshold
      dissociation energy as Maiba.Na(+)(H(2)O). These results indicate that the
      threshold dissociation energy for loss of a water molecule from these salt-bridge
      complexes is approximately 1 kcal/mol less than that for loss of water from the
      charge-solvated complexes.

PMID- 14583056
TI  - A theoretical study of the NMR spin-spin coupling constants of the complexes
      [(NC)(5)Pt-Tl(CN)(n)](n-) (n = 0-3) and [(NC)(5)Pt-Tl-Pt(CN)(5)](3-): a lesson on
      environmental effects.
AB  - The molecular geometries and the nuclear spin-spin coupling constants of the
      complexes [(NC)(5)Pt-Tl(CN)(n)](n-), n = 0-3, and the related system [(NC)(5)Pt
      Tl-Pt(CN)(5)](3-) are studied. These complexes have received considerable
      interest since the first characterization of the n = 1 system by Glaser and co
      workers in 1995 [J. Am. Chem. Soc. 1995, 117, 7550-7551]. For instance, these
      systems exhibit outstanding NMR properties, such as extremely large Pt-Tl spin
      spin coupling constants. For the present work, all nuclear spin-spin coupling
      constants J(Pt-Tl), J(Pt-C), and J(Tl-C) have been computed by means of a two
      component relativistic density functional approach. It is demonstrated by the
      application of increasingly accurate computational models that both the huge J(Pt
      Tl) for the complex (NC)(5)Pt-Tl and the whole experimental trend among the
      series are entirely due to solvent effects. An approximate inclusion of the bulk
      solvent effects by means of a continuum model, in addition to the direct
      coordination, proves to be crucial. Similarly drastic effects are reported for
      the coupling constants between the heavy atoms and the carbon nuclei. A
      computational model employing the statistical average of orbital-dependent model
      potentials (SAOP) in addition to the solvent effects allows to accurately
      reproduce the experimental coupling constants within reasonable limits.

PMID- 14583058
TI  - Synergistic effects in multicomponent electrocatalysts: the Pb-Ir-O system.
AB  - The ionic interactions were studied in aqueous solutions of Na(3)IrCl(6) +
      Pb(NO(3))(2) in order to develop a facilitated electrosynthesis of iridium-based
      catalytic surfaces. Spectroscopic studies indicated that ion pair charge-transfer
      complexes [IrCl(6)(3-)]-Pb(II) (K = 6 x 10(3)) and [Ir(H(2)O)Cl(5)(2-)]-Pb(II) (K
      = 2 x 10(3)) were formed in fresh and aged solutions, respectively.
      Electrochemical studies showed that interactions between the Ir(H(2)O)Cl(5)(2-)
      and Pb(II) species lead to synergistic lowering of the overpotential that was
      necessary for nucleation and growth of mixed metal oxide PbIrOx on the surface of
      glassy carbon electrodes. The Ir:Pb stoichiometry of the PbIrOx surface films was
      the same (1:1) as that of the high-temperature phase of Pb-Ir-O pyrochlore.
      Compared to IrOx, the PbIrOx films displayed enhanced catalytic activity toward
      the electrooxidation of carbohydrates. This was ascribed to synergism that
      involved retention of carbohydrate molecules at the Pb(II) sites of a PbIrOx film
      and oxidation at the adjacent Ir(IV) sites. The synergistic electroplating
      utilizing interactions between the partially aquated transition metal complex and
      posttransition metal ion represents a new synthetic route to highly homogeneous
      and reactive films of mixed metal oxides.

PMID- 14583057
TI  - Ultrafast excited-state dynamics of adenine and monomethylated adenines in
      solution: implications for the nonradiative decay mechanism.
AB  - The DNA base adenine and four monomethylated adenines were studied in solution at
      room temperature by femtosecond pump-probe spectroscopy. Transient absorption at
      visible probe wavelengths was used to directly observe relaxation of the lowest
      excited singlet state (S(1) state) populated by a UV pump pulse. In H(2)O,
      transient absorption signals from adenine decay biexponentially with lifetimes of
      0.18 +/- 0.03 ps and 8.8 +/- 1.2 ps. In contrast, signals from monomethylated
      adenines decay monoexponentially. The S(1) lifetimes of 1-, 3-, and 9
      methyladenine are similar to one another and are all below 300 fs, while 7
      methyladenine has a significantly longer lifetime (tau = 4.23 +/- 0.13 ps). On
      this basis, the biexponential signal of adenine is assigned to an equilibrium
      mixture of the 7H- and 9H-amino tautomers. Excited-state absorption (ESA) by 9
      methyladenine is 50% stronger than by 7-methyladenine. Assuming that ESA by the
      corresponding tautomers of adenine is unchanged, we estimate the population of 7H
      adenine in H(2)O at room temperature to be 22 +/- 4% (estimated standard
      deviation). To understand how the environment affects nonradiative decay, we
      performed the first solvent-dependent study of nucleobase dynamics on the
      ultrafast time scale. In acetonitrile, both lowest energy tautomers of adenine
      are present in roughly similar proportions as in water. The lifetimes of the 9
      substituted adenines depend somewhat more sensitively on the solvent than those
      of the 7-substituted adenines. Transient signals for adenine in H(2)O and D(2)O
      are identical. These solvent effects strongly suggest that excited-state
      tautomerization is not an important nonradiative decay pathway. Instead, the data
      are most consistent with electronic energy relaxation due to state crossings
      between the optically prepared (1)pipi* state and one or more (1)npi* states and
      the electronic ground state. The pattern of lifetimes measured for the
      monomethylated adenines suggests a special role for the (1)npi* state associated
      with the N7 electron lone pair.

PMID- 14583059
TI  - Intramolecular directional forster resonance energy transfer at the single
      molecule level in a dendritic system.
AB  - We report on the directional Forster resonance energy transfer (FRET) process
      taking place in single molecules of a first (T1P4) and a second (T2P8) generation
      of a perylenemonoimide (P)-terrylenediimide (T)-based dendrimer in which the
      chromophores are separated by rigid polyphenylene arms. At low excitation powers,
      single-molecule detection and spectroscopy of T1P4 and T2P8 dendrimers point to a
      highly efficient directional FRET from P donors to the central T acceptor,
      optical excitation at 488 nm resulting in exclusively acceptor emission in the
      beginning of the detected fluorescence intensity. Donor emission is seen only
      upon the bleaching of the acceptor. High-resolution time-resolved single-molecule
      fluorescence data measured with a microchannel plate photomultiplier reveal, for
      T2P8, a broad range of FRET rates as a result of a broad range of distances and
      orientations experienced by the donor-acceptor dendrimers when immobilized in a
      polymer matrix. Single-molecule data from T2P8 on 488 nm excitation are
      indicative for the presence, after terrylenediimide bleaching, of a P-P excited
      dimer characterized by a broad emission spectrum peaking around 600 nm and by
      fluctuating fluorescence decay times. At high excitation powers, single T1P4 and
      T2P8 molecules display simultaneous emission from both donor and acceptor
      chromophores. The effect, called "exciton blockade", occurs due to the presence
      of multiple excitations in a single molecule.

PMID- 14583061
TI  - Health risks of counterfeit pharmaceuticals.
AB  - Pharmaceutical products are not exempt from the practice of counterfeiting. In
      recent years, many reports have become available demonstrating the presence of
      fake medicines on the market. Several studies have demonstrated that they are
      quite often of bad quality. It is estimated that 5% of all world trade in branded
      goods is counterfeit, leading to huge financial losses for the pharmaceutical
      industry. But much more important, from a public health point of view, is that
      history has shown that such products may lead to a great health risk. The essence
      of counterfeit products and the reason they are so dangerous is the complete
      absence of quality control, since they are often indistinguishable from the
      genuine product. The existence of counterfeit drugs has long been ignored both by
      the pharmaceutical industry and by drug regulatory authorities. At present
      initiatives are being taken, nationally and internationally, to curb
      counterfeiting. It is now realised that a strong regulatory agency is essential,
      but the initiatives can only be successful if all parties concerned actively co
      operate.

PMID- 14583062
TI  - Changes in toxicity and effectiveness with timing of drug administration:
      implications for drug safety.
AB  - The effectiveness and toxicity of many drugs can vary depending on the time of
      administration in relation to 24-hour rhythms of biochemical, physiological and
      behavioural processes under the control of the circadian clock. Such
      chronopharmacological phenomena are influenced by not only the pharmacokinetics
      but also pharmacodynamics of medications. Chronotherapy is especially relevant
      when the risk and/or intensity of the symptoms of disease vary predictably over
      time as exemplified by allergic rhinitis, arthritis, asthma, myocardial
      infarction, congestive heart failure, stroke and peptic ulcer disease. Morning,
      once-daily administration of corticosteroids results in little adrenocortical
      suppression, while the same daily dose split into four equal doses to coincide
      with daily meals and bedtime results in significant hypothalamus-pituitary
      adrenal axis suppression. In a randomised, multicentre trial involving patients
      with previously untreated metastases from colorectal cancer, the chronomodulated
      infusion of oxaliplatin, fluorouracil and folinic acid was compared with a
      constant-rate infusion method. Adverse effects such as stomatitis and peripheral
      sensory neuropathy were lower and objective response was higher with
      chronotherapy as compared with the fixed-rate infusion. The merit of
      chronomodulated infusion is supported by the 24-hour rhythm of DNA synthesis and
      the activity of dehydropyrimidine dehydrogenase, which brings about the
      intracellular catabolism of fluorouracil. On the other hand, haloperidol and
      selective serotonin reuptake inhibitors have diverse effects on sleep continuity
      and nocturnal arousals. Although interferon also alters the clock function, this
      disruptive effect can be overcome by devising an administration regimen that
      minimises adverse drug effects on clock function. Thus, one approach to
      increasing the efficiency of pharmacotherapy is the administration of drugs at
      times at which they are most effective and/or best tolerated.

PMID- 14583063
TI  - Aluminium in over-the-counter drugs: risks outweigh benefits?
AB  - In the early 1970s, aluminium toxicity was first implicated in the pathogenesis
      of clinical disorders in patients with chronic renal failure involving bone
      (renal osteomalacia) or brain tissue (dialysis encephalopathy). Before that time
      the toxic effects of aluminium ingestion were not considered to be a major
      concern because absorption seemed unlikely to occur. Meanwhile, aluminium
      toxicity has been investigated in countless epidemiological and clinical studies
      as well as in animal experiments and many papers have been published on the
      subject. It is now commonly acknowledged that aluminium toxicity can be induced
      by infusion of aluminium-contaminated dialysis fluids, by parenteral nutrition
      solutions, and by oral exposure as a result of aluminium-containing
      pharmaceutical products such as aluminium-based phosphate binders or antacid
      intake. Over-the-counter antacids are the most important source for human
      aluminium exposure from a quantitative point of view. However, aluminium can act
      as a powerful neurological toxicant and provoke embryonic and fetal toxic effects
      in animals and humans after gestational exposure. Despite these facts, the
      patient information leaflets from European antacids that are available OTC show
      substantial differences regarding warnings from aluminium toxicity. It seems
      advisable that all patients should receive the same information on aluminium
      toxicity from patient information leaflets, in particular with regard to the
      increased absorption through concomitant administration with citrate-containing
      beverages and the use of such antacids during pregnancy.

PMID- 14583065
TI  - Stimulating adverse drug reaction reporting: effect of a drug safety bulletin and
      of including yellow cards in prescription pads.
AB  - BACKGROUND: The effectiveness of voluntary reporting systems in pharmacovigilance
      highly depends on the number of assembled reports. AIM: The aim of this study was
      to measure the effect of the periodical distribution of a bulletin on drug safety
      issues and of including yellow cards in prescription pads on the rate of adverse
      drug reaction (ADR) reporting. STUDY DESIGN AND METHODS: The Catalan Centre of
      Pharmacovigilance began its activities at the end of 1982. Since 1985, an ADR
      bulletin (ADRB) has been mailed approximately quarterly to all physicians in its
      catchment area, with one yellow card enclosed. Additionally, from 1991-1994, a
      yellow card was included in the prescription pads of the Catalan Health Service.
      Time series methodology, with adjustment of the monthly number of reports to an
      Auto-Regressive Integrated Moving Average (ARIMA) model, was used to evaluate the
      effect of these two measures. RESULTS: From January 1983-October 1995, 6240
      spontaneous ADR reports were received, and 41 issues of the ADRB were sent out.
      Initially, the mean monthly spontaneous ADR reporting rate was 34.4 (SD = 14.1; n
      = 106 months). After the inclusion of yellow cards in prescription pads, the mean
      monthly spontaneous ADR reporting rate increased to 53.9 (SD = 14.4; n = 48
      months). According to an ARIMA model, when a bulletin was send out (MONTH1), a
      mean increase of 9.4 reports was produced in that month, plus 12.3 additional
      reports in the following month (MONTH2), and 6.3 in the second month after
      sending the ADRB (MONTH3). A yellow card in the prescription pads elicits a
      monthly mean increase of 19.8 in the number of reports. CONCLUSIONS: The present
      study suggests that ADRBs elicit a temporal increase of the ADR reporting rate.
      Including a yellow card in prescription pads was followed by an even greater
      increase in the reporting rate, possibly because it guarantees that yellow cards
      are available at the workplace.

PMID- 14583064
TI  - A benefit-risk assessment of sibutramine in the management of obesity.
AB  - Obesity is a multifactorial, chronic disorder that has reached epidemic
      proportions in most industrialised countries and is threatening to become a
      global epidemic. Clinical management of obese patients is complex and serious
      doubts have arisen with regard to safety and efficacy of drug therapy. Following
      the withdrawal of fenfluramine and dexfenfluramine in 1997, interest has focused
      on novel anti-obesity drugs. Pharmacological approaches to the management of
      obesity can, in broad terms, use different distinct strategies: firstly, to
      reduce energy intake; secondly, to increase energy expenditure; and thirdly, to
      alter the partitioning of nutrients between fat and lean tissue. Sibutramine is a
      serotonin-noradrenaline (norepinephrine) reuptake inhibitor indicated for the
      management of obesity in conjunction with a reduced calorie diet. The
      pharmacological mechanisms by which sibutramine exerts its weight loss effect are
      likely due to a combination of reduced appetite, feelings of satiety and possibly
      the induction of thermogenesis. The efficacy of sibutramine for inducing initial
      weight loss and the subsequent maintenance of weight loss is well proven in short
      and long-term clinical trials of up to 2 years' duration. Most individual
      placebo-controlled trials and pooled estimates found that the drug produced
      statistically significant greater weight loss than placebo at all observed
      endpoints (weighted mean difference for weight change at 8 weeks: -3.4 kg; mean
      difference range for weight change at 6 months: -4.0 to -9.1 kg; and at 1 year: 
      4.1 to -4.8 kg). The most frequent dosage regimen in these trials was 10-20 mg
      daily. Findings suggested a dose-effect relationship in terms of weight loss.
      Sibutramine was also associated with better weight maintenance relative to
      placebo (statistically significant difference). Results from mainly small trials
      showed that sibutramine produced more favourable outcomes in terms of loss of fat
      mass, reduction in body mass index and loss of > or = 5-10% of initial
      bodyweight. The most commonly reported adverse effects of sibutramine are
      headache, constipation and nausea. Certain adverse events associated with the
      nervous system, including dizziness, dry mouth and insomnia, are reported by > 5%
      of patients receiving sibutramine. Increases in blood pressure and heart rate
      were possible adverse effects that require regular monitoring especially in obese
      hypertensive patients. Neither left-sided cardiac valve disease nor primary
      pulmonary hypertension was associated with the use of sibutramine. The assessment
      of the benefit-risk profile of sibutramine remained positive, although the
      product must be kept under regular review.

PMID- 14583066
TI  - Declaration of fructose and fructose-related adverse effects in commercial drug
      preparations in European countries.

PMID- 14583067
TI  - Balancing gastroprotection and cardioprotection with selective cyclo-oxygenase-2
      inhibitors: clinical implications.
AB  - NSAIDs have been the mainstay of treatment in the management of pain and
      inflammation associated with chronic inflammatory disorders. They are effective.
      However, complications arising from chronic NSAID use are common and are
      primarily due to gastrointestinal (GI) toxicity in the form of gastritis, peptic
      erosions and ulceration and GI bleeds. GI toxicity has been attributed to the
      blockade of the cyclo-oxygenase (COX)-1-mediated generation of the cytoprotective
      prostanoids, such as prostaglandin (PG) E2 and PGI2 (prostacyclin). More
      recently, selective COX-2 inhibitors ('coxibs') were designed to inhibit the
      production of COX-2-dependent inflammatory prostanoids and to leave intact the
      cytoprotective COX-1 products. The coxibs, while exhibiting similar efficacy to
      traditional NSAIDs in controlled clinical trials of their efficacy in chronic
      inflammatory conditions, such as osteoarthritis and rheumatoid arthritis, have
      been associated with a reduced incidence of surrogate or actual indices of GI
      toxicity. However, concerns regarding cardiovascular safety in high-risk patients
      have evolved. These concerns were driven initially by the concept that inhibition
      of COX-2-derived endothelial PGI2 without concomitant inhibition of platelet
      thromboxane A2 would result in increased cardiovascular risk. This was borne out
      in the Vioxx Gastrointestinal Outcomes Research study of rofecoxib, but not
      demonstrated in the Celecoxib Long Term Arthritis Safety Study trial. Further
      elucidation of the relative roles of COX-1- and COX-2-generated prostanoids has
      enabled a greater understanding of the biology of these pathways. However, it is
      still not completely clear how this understanding may be appropriately translated
      into clinical medicine.

PMID- 14583068
TI  - Use of antibiotic and analgesic drugs during lactation.
AB  - During lactation, multiple situations can arise that require maternal
      pharmacological treatment. Because of the many health advantages of human milk to
      infants, breast feeding should be interrupted only when the needed drug might be
      harmful to the nursing child and exposure via the breast milk will be sufficient
      to pose a risk. Since the majority of drugs have not been shown to cause adverse
      effects when used during lactation, and even temporary interruption of breast
      feeding can be difficult for the nursing dyad, decisions regarding maternal
      medication use during breast feeding should be based on accurate and up-to-date
      information. This article reviews available data on the most commonly used
      antibiotics and analgesics. The use of most antibiotics is considered compatible
      with breast feeding. Penicillins, aminopenicillins, clavulanic acid,
      cephalosporins, macrolides and metronidazole at dosages at the low end of the
      recommended dosage range are considered appropriate for use for lactating women.
      Fluoroquinolones should not be administered as first-line treatment, but if they
      are indicated, breast feeding should not be interrupted because the risk of
      adverse effects is low and the risks are justified. Paracetamol (acetaminophen),
      low-dose aspirin (acetylsalicylic acid) [up to 100 mg/day] and short-term
      treatment with NSAIDs, codeine, morphine and propoxyphene are considered
      compatible with breast feeding. Safer alternatives should be considered instead
      of dipyrone, aspirin at a dosage >100 mg/day and pethidine (meperidine). In the
      light of the many safe alternatives for pain control, breast-feeding mothers
      should not be allowed to experience pain or be made to feel that they must choose
      between analgesia and breast feeding.

PMID- 14583069
TI  - Reducing medication errors: a regional approach for hospitals.
AB  - Since the Institute of Medicine's report, To Err Is Human, and the subsequent
      publication, Crossing the Quality Chasm, the subject of reducing medical errors
      has gained considerable attention from patients, healthcare providers, employers
      and government organisations in the US. Most nonoperative errors are related to
      medications. Medication errors lead not only to negative repercussions
      subjectively experienced by both the patient and the healthcare staff, but also
      to additional expenditures due to complications. Education, adapting new safety
      systems and technology, and having clinical pharmacists play a larger role in the
      medication process can all help in solving the problem of medication errors.
      Designing and executing a rational system to reduce medication errors is
      particularly germane in the current era of increased demands for quality
      healthcare in the setting of cost-containment pressures. In the Delaware Valley
      (Philadelphia and surrounding area) of Pennsylvania, USA, a consortium of
      healthcare providers in cooperation with the Health Care Improvement Foundation
      (HCIF), and two non-profit oganisations--the ECRI (formerly the Emergency Care
      Research Institute) and the Institute for Safe Medication Practices (ISMP)--have
      combined to establish and promote safe medication practices under a programme
      known as the Regional Medication Safety Program for Hospitals. At the core of the
      programme are 16 medication safety goals, which centre on establishing an
      institutional culture of safety, modifying infrastructure and clinical practice
      to reflect this culture, and using technology to facilitate these changes. It is
      believed that this rational campaign to improve patient safety may serve as a
      paradigm for other regions around the world.

PMID- 14583071
TI  - Risks versus benefits of NSAIDs including aspirin in myocarditis: a review of the
      evidence from animal studies.
AB  - NSAIDs, including aspirin (acetylsalicylic acid), are frequently used and
      effective in a broad variety of inflammatory diseases, i.e. rheumatic carditis
      and pericarditis. Myocarditis may constitute another suitable indication for
      NSAIDs in order to relieve the symptoms of the presumed viral infection or
      because pericardial effusion is often associated with this condition. However,
      concerns have been raised about their indiscriminate use in myocarditis. To
      clarify this issue, we conducted a systematic review of the literature concerning
      myocarditis, aspirin and NSAIDs. We examined five animal studies of NSAIDs
      (indomethacin and ibuprofen) and aspirin in coxsackievirus B3- and B4-induced
      myocarditis. These studies indicated a deleterious effect of NSAIDs and aspirin
      in this setting, demonstrating a 2- to 3-fold increase in inflammation, myocytes
      necrosis and even mortality when compared with placebo. This possible deleterious
      effect was more predominant when NSAIDs or aspirin were administered during the
      acute and subacute phases of myocarditis; however, it was still noted when NSAIDs
      were administered during the late phase of the disease (the effect of aspirin was
      not evaluated in late phase studies). According to these animal studies, such
      effect might be attributed to decreased viral clearance (possibly via interferon
      inhibition) and/or exaggerated cytotoxic response (via interleukin-2 or
      inhibition of suppressor cells factors) and/or coronary artery spasm. We found
      one animal study looking at autoimmune myocarditis and it did not demonstrate any
      beneficial or detrimental effect of aspirin. Moreover, recent data suggest that
      aspirin and NSAIDs may counteract part of the efficacy of ACE inhibitors and be
      deleterious in chronic heart failure. Taken together, these studies point to a
      possible deleterious effect of aspirin and NSAIDs in human myocarditis. In view
      of these animal studies and in the absence of controlled studies of aspirin or
      NSAIDs in human myocarditis, we do not recommend indiscriminate treatment with
      NSAIDs or high-dose aspirin in patients with myocarditis where there is no or
      minimal associated pericarditis.

PMID- 14583070
TI  - Benefit-risk assessment of transdermal fentanyl for the treatment of chronic
      pain.
AB  - Transdermal fentanyl is effective and well tolerated for the treatment of chronic
      pain caused by malignancy and non-malignant conditions when administered
      according to the manufacturer's recommendations. Compared with oral opioids, the
      advantages of transdermal fentanyl include a lower incidence and impact of
      adverse effects (constipation, nausea and vomiting, and daytime drowsiness), a
      higher degree of patient satisfaction, improved quality of life, improved
      convenience and compliance resulting from administration every 72 hours, and
      decreased use of rescue medication. Transdermal fentanyl is a useful analgesic
      for cancer patients who are unable to swallow or have gastrointestinal problems.
      Transdermal fentanyl forms a depot within the upper skin layers before entering
      the microcirculation. Therapeutic blood levels are attained 12-16 hours after
      patch application and decrease slowly with a half-life of 16-22 hours following
      removal. Patients with chronic pain should be titrated to adequate relief with
      short-acting oral or parenteral opioids prior to the initiation of transdermal
      fentanyl in order to prevent exacerbations of pain or opioid-related adverse
      effects. Transdermal fentanyl can then be initiated based on the 24-hour opioid
      requirement once adequate analgesia has been achieved. The prolonged elimination
      of transdermal fentanyl can become problematic if patients develop opioid-related
      adverse effects, especially hypoventilation. Adverse effects do not improve
      immediately after patch removal and may take many hours to resolve. Patients who
      experience opioid-related toxicity associated with respiratory depression should
      be treated immediately with an opioid antagonist such as naloxone and closely
      monitored for at least 24 hours. Because of the short half-life of naloxone,
      sequential doses or a continuous infusion of the opioid antagonist may be
      necessary. Transdermal fentanyl should be administered cautiously to patients
      with pre-existing conditions such as emphysema that may predispose them to the
      development of hypoventilation. Transdermal fentanyl is indicated only for
      patients who require continuous opioid administration for the treatment of
      chronic pain that cannot be managed with other medications. It is contraindicated
      in the management of acute and postoperative pain, as pain may decrease more
      rapidly in these circumstances than fentanyl blood levels can be adjusted,
      leading to the development of life-threatening hypoventilation. Cognitive and
      physical impairments such as confusion and abnormal co-ordination can occur with
      transdermal fentanyl. Therefore, patients should be instructed to refrain from
      driving or operating machinery immediately following the initiation of
      transdermal fentanyl, or after any dosage increase. Patients may resume such
      activities once the absence of these potential adverse effects is documented.

PMID- 14583073
TI  - Pet ownership: good for health?

PMID- 14583072
TI  - Effects of NSAIDs on the incidence of hospitalisations for renal dysfunction in
      users of ACE inhibitors.
AB  - INTRODUCTION: Although relatively safe, both NSAIDs and ACE inhibitors can cause
      renal dysfunction in patients with compromised renal function. Case reports
      indicate that the combined use of ACE inhibitors and NSAIDs increases the risk of
      renal dysfunction. It is not known how often and when renal dysfunction occurs in
      patients using a combination of ACE inhibitors and NSAIDs. OBJECTIVE: The
      objective of the study was to investigate the effects of NSAIDs on the incidence
      of hospitalisations due to renal dysfunction in patients treated with ACE
      inhibitors. STUDY DESIGN: Case-control study nested within a cohort of users of
      ACE inhibitors. PARTICIPANTS: All participants had at least two consecutive
      prescriptions for an ACE inhibitor. One hundred and forty-four cases were
      admitted to hospital for renal insufficiency during use of ACE inhibitors. There
      were 1189 randomly sampled control patients who did not have any hospital
      admission for renal dysfunction during use of ACE inhibitors. MAIN OUTCOME
      MEASURES: The risk for hospitalisation for renal dysfunction associated with
      exposure to NSAIDs in patients receiving ACE inhibitors was expressed as odds
      ratios (OR). RESULTS: Of 144 cases, a total of 32 (22.2%) received NSAIDs in the
      90 days before hospital admission for renal dysfunction. Recent start (<90 days)
      of an NSAID was associated with an increased risk of admission for renal
      dysfunction (adjusted OR 2.2; 95% CI 1.1-4.5). The increased risk was most
      pronounced in patients aged >70 years (adjusted OR 2.7; 95% CI 1.0-7.2). For
      patients who started NSAIDs and were dispensed at least three prescriptions in
      the 90 days preceding hospitalisation an adjusted OR of 7.1 (95% CI 1.8-28.7) was
      observed. CONCLUSIONS: This study strongly suggests an increased risk for
      hospitalisation for renal insufficiency in patients receiving ACE inhibitors who
      start using NSAIDs. Elderly patients receiving several prescriptions for NSAIDs
      in a short period of time are particularly at risk. Renal function should be
      closely monitored in these patients.

PMID- 14583074
TI  - Cardiac arrest in Australian hospitals.

PMID- 14583075
TI  - Duchenne muscular dystrophy: hopes for the sesquicentenary.

PMID- 14583077
TI  - Cardiac arrest resuscitation policies and practices: a survey of Australian
      hospitals.
AB  - OBJECTIVE: To describe the policy and practice relating to cardiopulmonary
      resuscitation (CPR) and defibrillation in cardiac arrest in Australian hospitals.
      DESIGN: Cross-sectional postal survey conducted in December 2001, using a semi
      structured, four-page questionnaire. PARTICIPANTS: Australian hospitals with more
      than 10 beds. MAIN OUTCOME MEASURES: Type of defibrillator; provision of
      CPR/defibrillation training for healthcare professionals; hospital policy as to
      who can use the defibrillator. RESULTS: Of the 878 hospitals surveyed, 665 (76%)
      responded. All but one hospital indicated that CPR training was provided for
      nursing staff, with 12-monthly or more frequent updates; only 55% of hospitals
      (366) indicated that CPR training was provided for doctors. 21 of the 665
      responding hospitals (3.2%) indicated that they did not have a defibrillator. 43%
      of hospitals had one or more defibrillators with shock advisory capacity (ie,
      automated external defibrillators [AEDs]). Of the 644 hospitals with
      defibrillators, 16% (101) indicated that registered nurses were not permitted to
      defibrillate; this included 9% of hospitals with AEDs. CONCLUSIONS: The
      importance of CPR in cardiac arrest has been accepted by Australian hospitals,
      but the overwhelming evidence that "time to defibrillation" is the single most
      important determinant of cardiac arrest outcome seems less accepted. All
      Australian hospitals should review their resuscitation policies and practices to
      reflect this fact, with defibrillation by nurses, who are usually first on the
      scene, providing the best opportunity to minimise time to defibrillation.

PMID- 14583076
TI  - Pet ownership and risk factors for cardiovascular disease: another look.
AB  - OBJECTIVE: To test the claim that pet ownership reduces cardiovascular risk.
      DESIGN: Community survey. PARTICIPANTS: 2528 adults aged 40-44 years and 2551
      aged 60-64 years who lived in the Australian Capital Territory and Queanbeyan,
      New South Wales, and were drawn randomly from the Australian electoral roll in
      2000 and 2001. MAIN OUTCOME MEASURES: Sociodemographic measures, including pet
      ownership, and measures of physical health (including body mass index [BMI],
      alcohol and cigarette consumption, and levels of physical activity). Two readings
      of diastolic and systolic blood pressure were also taken. RESULTS: While pet
      owners and non-pet owners had similar levels of systolic blood pressure, those
      with pets had significantly higher diastolic blood pressure. Pet owners also had
      higher BMI and were more likely to smoke. While those with pets undertook more
      mild physical activity, they continued to have significantly higher diastolic
      blood pressure after controlling for hypertensive risk factors. CONCLUSIONS: In
      this study, we found no evidence that pet ownership per se is associated with
      cardiovascular health benefits. Rather, pet owners had higher diastolic blood
      pressure than those without pets. It is likely that this increased health risk is
      linked to other hypertensive risk factors that are only indirectly associated
      with pet ownership.

PMID- 14583078
TI  - Achieving equity in the Australian healthcare system.

PMID- 14583079
TI  - "Cancer in the family" and genetic testing: implications for life insurance.
AB  - The potential for discrimination when applying for insurance can be of concern
      for individuals with a family history of cancer or of a genetic disorder and who
      are considering genetic counselling or genetic testing. The actual incidence of
      "genetic discrimination", however, is not known, despite considerable media
      coverage of this issue. The clinical details required by insurers have received
      less attention. We obtained primary application and personal statement forms used
      by 21 different underwriters of voluntary life insurance and found substantial
      differences in the information requested about family history and genetic
      testing. All insurance applications, however, contained a duty of disclosure that
      would require revealing the result, if known by the applicant, of a genetic test
      in a family member. Therefore, decisions made by family members can affect
      insurance applications, and people considering genetic testing may also need to
      consider the implications of the results for other family members. Health
      practitioners should balance the potential benefits of appropriate genetic
      testing against potential restriction to life and income-protection insurance
      when advising people about genetic testing.

PMID- 14583080
TI  - Ectopic parathyroid adenoma localised with sestamibi SPECT and image-fused
      computed tomography.
AB  - Confident localisation of ectopic parathyroid adenomas, particularly those
      outside the neck, can be difficult. Even preoperative radiological imaging may
      not be helpful, as there are few characteristic findings. We report a case in
      which hyperfunctioning ectopic parathyroid tissue in the mediastinum was detected
      with technetium-99m-sestamibi single-photon emission computed tomography and
      accurately localised non-invasively with image-fused computed tomography. This
      technique directly modified management.

PMID- 14583081
TI  - Evidence-based guidelines for fixing broken hips: an update.
AB  - OBJECTIVE: To update evidence-based guidelines for the treatment of proximal
      femoral fractures published in the Journal in 1999. DATA SOURCES: Systematic
      literature search of MEDLINE, CINAHL and EMBASE from January 1996 to September
      2001 and the Cochrane Database of Systematic Reviews (most recent issue searched 
      Issue 2, 2002). STUDY SELECTION: Randomised controlled trials and meta-analyses
      of all aspects of acute-care hospital treatment and rehabilitation of proximal
      femoral fractures among subjects aged 50 years and over with proximal femoral
      fractures not associated with metastatic disease or multiple trauma. DATA
      EXTRACTION: All studies were read independently by two reviewers. Reviewers
      recorded individual study results, and an assessment of study quality and
      treatment conclusions according to Cochrane Collaboration protocols. If
      necessary, a third review was performed to reach consensus. RESULTS: 93 new
      studies were identified and 82 met our inclusion criteria. Recommendations for
      thromboprophylaxis, anaesthesia, surgical fixation of fractures and nutritional
      status have been altered to incorporate new evidence. Recommendations have been
      added regarding postoperative blood transfusion, the management of
      subtrochanteric fractures, and the type of surgical swabs which should be used.
      CONCLUSIONS: Although there have been few significant changes to the previous
      recommendations, updating the guidelines has required substantial effort. The
      common clinical problem of hip fracture should be treated according to the most
      up-to-date evidence to achieve the best possible outcomes and optimal utilisation
      of limited resources. Guideline updates also require resourcing.

PMID- 14583082
TI  - Major pulmonary embolism and shock. Persistent hypotension after thrombolysis
      treated with improvised mechanical fragmentation of thrombus.

PMID- 14583084
TI  - General practice is not in crisis.

PMID- 14583083
TI  - 3: Preventing complications of diabetes.
AB  - Diabetes complications are common and almost triple the annual cost of managing
      diabetes. Microvascular complications are the major risk in type 1 diabetes,
      while macrovascular complications are the major cause of morbidity and mortality
      in type 2 diabetes. Control of hyperglycaemia (target HbA(1c) level < or = 7%)
      and hypertension (target blood pressure < or = 130/80 mmHg) prevents
      microvascular complications in both types of diabetes; a multifactorial approach,
      comprising behaviour modification and pharmacological therapy for all risk
      factors, reduces the development of micro- and macrovascular complications in
      type 2 diabetes. The benefit of treating dyslipidaemia is at least as great in
      the diabetic population as in the non-diabetic population. Angiotensin-converting
      enzyme inhibitors and low-dose aspirin are indicated in people with diabetes and
      other cardiovascular risk factors. Regular annual screening for diabetes
      complications allows treatable disease to be identified. Aggressive management of
      hyperglycaemia and other risk factors can prevent many complications

PMID- 14583085
TI  - "Only a GP?": is the solution to the general practice crisis intellectual?

PMID- 14583086
TI  - Is general practice vocational training at risk?

PMID- 14583087
TI  - Back to the future.

PMID- 14583088
TI  - Badmouthing GPs.

PMID- 14583089
TI  - Integrated critical care: an approach to specialist cover for critical care in
      the rural setting.

PMID- 14583090
TI  - Transcriptional regulation of human mucin MUC4 by bile acids in oesophageal
      cancer cells is promoter-dependent and involves activation of the
      phosphatidylinositol 3-kinase signalling pathway.
AB  - Abnormal gastro-oesophageal reflux and bile acids have been linked to the
      presence of Barrett's oesophageal premalignant lesion associated with an increase
      in mucin-producing goblet cells and MUC4 mucin gene overexpression. However, the
      molecular mechanisms underlying the regulation of MUC4 by bile acids are unknown.
      Since total bile is a complex mixture, we undertook to identify which bile acids
      are responsible for MUC4 up-regulation by using a wide panel of bile acids and
      their conjugates. MUC4 apomucin expression was studied by immunohistochemistry
      both in patient biopsies and OE33 oesophageal cancer cell line. MUC4 mRNA levels
      and promoter regulation were studied by reverse transcriptase-PCR and transient
      transfection assays respectively. We show that among the bile acids tested,
      taurocholic, taurodeoxycholic, taurochenodeoxycholic and glycocholic acids and
      sodium glycocholate are strong activators of MUC4 expression and that this
      regulation occurs at the transcriptional level. By using specific pharmacological
      inhibitors of mitogen-activated protein kinase, phosphatidylinositol 3-kinase,
      protein kinase A and protein kinase C, we demonstrate that bile acid-mediated up
      regulation of MUC4 is promoter-specific and mainly involves activation of
      phosphatidylinositol 3-kinase. This new mechanism of regulation of MUC4 mucin
      gene points out an important role for bile acids as key molecules in targeting
      MUC4 overexpression in early stages of oesophageal carcinogenesis.

PMID- 14583091
TI  - Phosphorylation of 20S proteasome alpha subunit C8 (alpha7) stabilizes the 26S
      proteasome and plays a role in the regulation of proteasome complexes by gamma
      interferon.
AB  - In animal cells there are several regulatory complexes which interact with 20S
      proteasomes and give rise to functionally distinct proteasome complexes. gamma
      Interferon upregulates three immuno beta catalytic subunits of the 20S proteasome
      and the PA28 regulator, and decreases the level of 26S proteasomes. It also
      decreases the level of phosphorylation of two proteasome alpha subunits, C8
      (alpha7) and C9 (alpha3). In the present study we have investigated the role of
      phosphorylation of C8 by protein kinase CK2 in the formation and stability of 26S
      proteasomes. An epitope-tagged C8 subunit expressed in mammalian cells was
      efficiently incorporated into both 20S proteasomes and 26S proteasomes.
      Investigation of mutants of C8 at the two known CK2 phosphorylation sites
      demonstrated that these are the two phosphorylation sites of C8 in animal cells.
      Although phosphorylation of C8 was not absolutely essential for the formation of
      26S proteasomes, it did have a substantial effect on their stability. Also, when
      cells were treated with gamma-interferon, there was a marked decrease in
      phosphorylation of C8, a decrease in the level of 26S proteasomes, and an
      increase in immunoproteasomes and PA28 complexes. These results suggest that the
      down-regulation of 26S proteasomes after gamma-interferon treatment results from
      the destabilization that occurs after dephosphorylation of the C8 subunit.

PMID- 14583092
TI  - Modulation of human insulin receptor substrate-1 tyrosine phosphorylation by
      protein kinase Cdelta.
AB  - Non-esterified fatty acid (free fatty acid)-induced activation of the novel PKC
      (protein kinase C) isoenzymes PKCdelta and PKCtheta correlates with insulin
      resistance, including decreased insulin-stimulated IRS-1 (insulin receptor
      substrate-1) tyrosine phosphorylation and phosphoinositide 3-kinase activation,
      although the mechanism(s) for this resistance is not known. In the present study,
      we have explored the possibility of a novel PKC, PKCdelta, to modulate directly
      the ability of the insulin receptor kinase to tyrosine-phosphorylate IRS-1. We
      have found that expression of either constitutively active PKCdelta or wild-type
      PKCdelta followed by phorbol ester activation both inhibit insulin-stimulated IRS
      1 tyrosine phosphorylation in vivo. Activated PKCdelta was also found to inhibit
      the IRS-1 tyrosine phosphorylation in vitro by purified insulin receptor using
      recombinant full-length human IRS-1 and a partial IRS-1-glutathione S-transferase
      fusion protein as substrates. This inhibition in vitro was not observed with a
      non-IRS-1 substrate, indicating that it was not the result of a general decrease
      in the intrinsic kinase activity of the receptor. Consistent with the hypothesis
      that PKCdelta acts directly on IRS-1, we show that IRS-1 can be phosphorylated by
      PKCdelta on at least 18 sites. The importance of three of the PKCdelta
      phosphorylation sites in IRS-1 was shown in vitro by a 75-80% decrease in the
      incorporation of phosphate into an IRS-1 triple mutant in which Ser-307, Ser-323
      and Ser-574 were replaced by Ala. More importantly, the mutation of these three
      sites completely abrogated the inhibitory effect of PKCdelta on IRS-1 tyrosine
      phosphorylation in vitro. These results indicate that PKCdelta modulates the
      ability of the insulin receptor to tyrosine-phosphorylate IRS-1 by direct
      phosphorylation of the IRS-1 molecule.

PMID- 14583093
TI  - Structure and function of human Vps20 and Snf7 proteins.
AB  - Snf7p (sucrose non-fermenting) and Vps20p (vacuolar protein-sorting) are small
      coil-coiled proteins involved in yeast MVB (multivesicular body) structure,
      formation and function. In the present study, we report the identification of
      three human homologues of yeast Snf7p, designated hSnf7-1, hSnf7-2 and hSnf7-3,
      and a single human Vps20p homologue, designated hVps20, that may have similar
      roles in humans. Immunofluorescence studies showed that hSnf7-1 and hSnf7-3
      localized in large vesicular structures that also co-localized with late
      endosomal/lysosomal structures induced by overexpressing an ATPase-defective Vps4
      A mutant. In contrast, overexpressed hVps20 showed a typical endosomal membrane
      staining pattern, and co-expression of hVps20 with Snf7-1 dispersed the large
      Snf7-staining vesicles. Interestingly, overexpression of both hSnf7 and hVps20
      proteins induced a post-endosomal defect in cholesterol sorting. To explore
      possible protein-protein interactions involving hSnf7 proteins, we used
      information from yeast genomic studies showing that yeast Snf7p can interact with
      proteins involved in MVB function. Using a glutathione S-transferase-capture
      approach with several mammalian homologues of such yeast Snf7p-interacting
      proteins, we found that all three hSnf7s interacted with mouse AIP1 [ALG-2
      (apoptosis-linked gene 2) interacting protein 1], a mammalian Bro1p [BCK1 (bypass
      of C kinase)-like resistance to osmotic shock]-containing protein involved in
      cellular vacuolization and apoptosis. Whereas mapping experiments showed that the
      N-terminus of AIP1 containing both a Bro1 and an alpha-helical domain were
      required for interaction with hSnf7-1, Snf7-1 did not interact with another human
      Bro1-containing molecule, rhophilin-2. Co-immunoprecipitation experiments
      confirmed the in vivo interaction of hSnf7-1 and AIP1. Additional
      immunofluorescence experiments showed that hSnf7-1 recruited cytosolic AIP1 to
      the Snf7-induced vacuolar-like structures. Together these results suggest that
      mammalian Vps20, AIP1 and Snf7 proteins, like their yeast counterparts, play
      roles in MVB function.

PMID- 14583094
TI  - New role for leucyl aminopeptidase in glutathione turnover.
AB  - A manganese-dependent cysteinyl-glycine hydrolysing activity has been purified to
      electrophoretic homogeneity from bovine lens. The characterization of the
      purified enzyme (molecular mass of the native protein, molecular mass of the
      subunit and extensive primary structure analysis) allowed the unequivocal
      attribution of the cysteinyl-glycine hydrolysing activity, which is usually
      associated with alanyl aminopeptidase (EC 3.4.11.2) or membrane-bound dipeptidase
      (EC 3.4.13.19), to LAP (leucyl aminopeptidase; EC 3.4.11.1). Analysis of the pH
      dependence of Cys-Gly hydrolysis catalysed by LAP, supported by a molecular
      modelling approach to the enzyme-substrate conformation, gave insights into the
      ability of the enzyme to recognize Cys-Gly as a substrate. Due to the
      effectiveness of LAP in hydrolysing Cys-Gly (K(m)=0.57 mM, kcat=6.0x10(3) min(-1)
      at pH 7.4 and 25 degrees C) with respect to other dipeptide substrates, a new
      role for this enzyme in glutathione turnover is proposed.

PMID- 14583096
TI  - BRCA1/2 mutation screening and LOH analysis of lung adenocarcinoma tissue in a
      multiple-cancer patient with a strong family history of breast cancer.
AB  - BACKGROUND: Germline mutations in BRCA1/2 greatly elevate risks of breast and
      ovarian cancers, but the role of these genes in tumourigenesis of other cancer
      types is still being investigated. OBJECTIVE: We report on an investigation of
      BRCA1/2 mutations and their loss of heterozygosity (LOH) in a patient with a
      strong family history of breast cancer who was diagnosed with consecutive primary
      cervical, ovarian and lung carcinomas. METHODS AND RESULTS: BRCA1/2 mutation
      screening of the proband revealed a common familial breast- and ovarian cancer
      associated germline BRCA2 mutation (3034del4bp). We then performed LOH analysis
      for BRCA2 in lung adenocarcinoma tissue of the patient. Using the laser-capture
      microdissection (LCM) technique, we obtained pure populations of neoplastic cells
      from which DNA could be extracted. Mutation analysis by denaturing high
      performance liquid chromatography (DHPLC) and direct sequencing revealed loss of
      the mutant allele in the adenocarcinoma tumour tissue. CONCLUSION: To our
      knowledge, this is the first report of investigation for LOH for BRCA2 in primary
      lung adenocarcinoma tissue of a patient with multiple primary tumours related to
      a familial germline BRCA2 mutation. Interestingly, it was the mutant, not the
      wild-type, allele which was lost in the lung adenocarcinoma tissue.

PMID- 14583095
TI  - Structural elucidation of novel phosphocholine-containing glycosylinositol
      phosphoceramides in filamentous fungi and their induction of cell death of
      cultured rice cells.
AB  - Novel ZGLs (zwitterionic glycosphingolipids) have been found in and extracted
      from the mycelia of filamentous fungi ( Acremonium sp.) isolated from soil. Five
      ZGLs (ZGL1-ZGL5) were structurally elucidated by sugar compositional analysis,
      methylation analysis, periodate oxidation, matrix-assisted laser-desorption
      ionization-time-of-flight MS, (1)H-NMR spectroscopy and fast-atom bombardment MS.
      Their chemical structures were as follows: GlcN(alpha1-2)Ins1-P-1Cer (ZGL1),
      Man(alpha1-6)GlcN(alpha1-2)Ins1-P-1Cer (ZGL2), Man(alpha1-6)Man(alpha1
      6)GlcN(alpha1-2)Ins1-P-1Cer (ZGL3), PC-->6Man(alpha1-6)GlcN(alpha1-2)Ins1- P 
      1Cer (ZGL4), and PC-->6Man(alpha1-6)Man(alpha1-6)GlcN(alpha1-2)Ins1-P-1Cer (ZGL5)
      (where Cer is ceramide and PC is phosphocholine). In addition, one acidic
      glycosphingolipid, which was the precursor of ZGLs, was also characterized as
      inositol-phosphoceramide. The core structure of the ZGLs, GlcN(alpha1-2)Ins1- P,
      is rather different from those found in other fungi, such as Man(alpha1-2)Ins1- P
      and Man(alpha1-6)Ins1- P. Interestingly, the terminal mannose residue of ZGL4 and
      ZGL5 was modified further with a PC group. The presence of PC-containing
      glycosylinositol-phosphoceramides has not been reported previously in any
      organism. The ceramide constituents of both ZGLs and acidic glycosphingolipid
      were essentially the same, and consisted of a 4-hydroxyoctadecasphinganine
      (phytosphingosine) as the sole sphingoid base and 2-hydroxytetracosanoic acid
      (>90%) as the major fatty acid. ZGLs were found to cause cell death in
      suspensions of cultured rice cells. The cell death-inducing activity of ZGLs is
      probably due to the characteristic glycan moiety of Man(alpha1-6)GlcN, and PC
      containing ZGLs had high activity. This study is the first to demonstrate that
      fungal glycosylinositol-phosphoceramides induce cell death in cultured rice
      cells.

PMID- 14583097
TI  - Performance of high-throughput DNA quantification methods.
AB  - BACKGROUND: The accuracy and precision of estimates of DNA concentration are
      critical factors for efficient use of DNA samples in high-throughput genotype and
      sequence analyses. We evaluated the performance of spectrophotometric (OD) DNA
      quantification, and compared it to two fluorometric quantification methods, the
      PicoGreen assay (PG), and a novel real-time quantitative genomic PCR assay (QG)
      specific to a region at the human BRCA1 locus. Twenty-Two lymphoblastoid cell
      line DNA samples with an initial concentration of approximately 350 ng/uL were
      diluted to 20 ng/uL. DNA concentration was estimated by OD and further diluted to
      5 ng/uL. The concentrations of multiple aliquots of the final dilution were
      measured by the OD, QG and PG methods. The effects of manual and robotic
      laboratory sample handling procedures on the estimates of DNA concentration were
      assessed using variance components analyses. RESULTS: The OD method was the DNA
      quantification method most concordant with the reference sample among the three
      methods evaluated. A large fraction of the total variance for all three methods
      (36.0-95.7%) was explained by sample-to-sample variation, whereas the amount of
      variance attributable to sample handling was small (0.8-17.5%). Residual error
      (3.2-59.4%), corresponding to un-modelled factors, contributed a greater extent
      to the total variation than the sample handling procedures. CONCLUSION: The
      application of a specific DNA quantification method to a particular molecular
      genetic laboratory protocol must take into account the accuracy and precision of
      the specific method, as well as the requirements of the experimental workflow
      with respect to sample volumes and throughput. While OD was the most concordant
      and precise DNA quantification method in this study, the information provided by
      the quantitative PCR assay regarding the suitability of DNA samples for PCR may
      be an essential factor for some protocols, despite the decreased concordance and
      precision of this method.

PMID- 14583098
TI  - A dominant negative mutant of TLK1 causes chromosome missegregation and
      aneuploidy in normal breast epithelial cells.
AB  - BACKGROUND: In Arabidopsis thaliana, the gene Tousled encodes a protein kinase of
      unknown function, but mutations in the gene lead to flowering and leaf morphology
      defects. We have recently cloned a mammalian Tousled-Like Kinase (TLK1B) and
      found that it phosphorylates specifically histone H3, in vitro and in vivo. We
      now report the effects that overexpression of a kinase-dead mutant of TLK1B
      mediates in a normal diploid cell line. RESULTS: Expression of a kinase-dead
      mutant resulted in reduction of phosphorylated histone H3, which could have
      consequences in mitotic segregation of chromosomes. When analyzed by FACS and
      microscopy, these cells displayed high chromosome number instability and
      aneuploidy. This phenomenon was accompanied by less condensed chromosomes at
      mitosis; failure of a number of chromosomes to align properly on the metaphase
      plate; failure of some chromosomes to attach to microtubules; and the occasional
      presentation of two bipolar spindles. We also used a different method (siRNA) to
      reduce the level of endogenous TLK1, but in this case, the main result was a
      strong block of cell cycle progression suggesting that TLK1 may also play a role
      in progression from G1. This block in S phase progression could also offer a
      different explanation of some of the later mitotic defects. CONCLUSIONS: TLK1 has
      a function important for proper chromosome segregation and maintenance of diploid
      cells at mitosis in mammalian cells that could be mediated by reduced
      phosphorylation of histone H3 and condensation of chromosomes, although other
      explanations to the phenotype are possible.

PMID- 14583099
TI  - LEAping to conclusions: a computational reanalysis of late embryogenesis abundant
      proteins and their possible roles.
AB  - BACKGROUND: The late embryogenesis abundant (LEA) proteins cover a number of
      loosely related groups of proteins, originally found in plants but now being
      found in non-plant species. Their precise function is unknown, though
      considerable evidence suggests that LEA proteins are involved in desiccation
      resistance. Using a number of statistically-based bioinformatics tools the
      classification of a large set of LEA proteins, covering all Groups, is reexamined
      together with some previous findings. Searches based on peptide composition
      return proteins with similar composition to different LEA Groups; keyword
      clustering is then applied to reveal keywords and phrases suggestive of the
      Groups' properties. RESULTS: Previous research has suggested that glycine is
      characteristic of LEA proteins, but it is only highly over-represented in Groups
      1 and 2, while alanine, thought characteristic of Group 2, is over-represented in
      Group 3, 4 and 6 but under-represented in Groups 1 and 2. However, for LEA Groups
      1 2 and 3 it is shown that glutamine is very significantly over-represented,
      while cysteine, phenylalanine, isoleucine, leucine and tryptophan are
      significantly under-represented. There is also evidence that the Group 4 LEA
      proteins are more appropriately redistributed to Group 2 and Group 3. Similarly,
      Group 5 is better found among the Group 3 LEA proteins. CONCLUSIONS: There is
      evidence that Group 2 and Group 3 LEA proteins, though distinct, might be
      related. This relationship is also evident in the overlapping sets of keywords
      for the two Groups, emphasising alpha-helical structure and, at a larger scale,
      filaments, all of which fits well with experimental evidence that proteins from
      both Groups are natively unstructured, but become structured under stress
      conditions. The keywords support localisation of LEA proteins both in the nucleus
      and associated with the cytoskeleton, and a mode of action similar to chaperones,
      perhaps the cold shock chaperones, via a role in DNA-binding. In general, non
      globular and low-complexity proteins, such as the LEA proteins, pose particular
      challenges in determining their functions and modes of action. Rather than
      masking off and ignoring low-complexity domains, novel tools and tool
      combinations are needed which are capable of analysing such proteins in their
      entirety.

PMID- 14583100
TI  - A knowledge discovery object model API for Java.
AB  - BACKGROUND: Biological data resources have become heterogeneous and derive from
      multiple sources. This introduces challenges in the management and utilization of
      this data in software development. Although efforts are underway to create a
      standard format for the transmission and storage of biological data, this
      objective has yet to be fully realized. RESULTS: This work describes an
      application programming interface (API) that provides a framework for developing
      an effective biological knowledge ontology for Java-based software projects. The
      API provides a robust framework for the data acquisition and management needs of
      an ontology implementation. In addition, the API contains classes to assist in
      creating GUIs to represent this data visually. CONCLUSIONS: The Knowledge
      Discovery Object Model (KDOM) API is particularly useful for medium to large
      applications, or for a number of smaller software projects with common
      characteristics or objectives. KDOM can be coupled effectively with other
      biologically relevant APIs and classes. Source code, libraries, documentation and
      examples are available at http://www.bcgsc.ca/bioinfo/software.

PMID- 14583102
TI  - Toward optimal health: the experts provide a current perspective on
      perimenopause. Interview by Jodi Godfrey Meisler.

PMID- 14583103
TI  - Phytoestrogens: potential benefits and implications for breast cancer survivors.
AB  - Phytoestrogens are a group of plant-derived substances that are structurally or
      functionally similar to estradiol. There has been much interest in the potential
      role of phytoestrogens in cancer prevention and treatment of estrogen-deficient
      states. This review summarizes the evidence for phytoestrogen risks and benefits
      relevant to the breast cancer survivor, including prevention of a second primary
      breast cancer or metastatic disease, reduction in menopausal symptoms, and
      interactions with tamoxifen. Epidemiological data suggest a breast cancer
      protective role for phytoestrogens, and there is some supporting clinical data,
      but they are far from conclusive. In addition, there is some evidence that
      genistein, the most prevalent isoflavone in soy, can stimulate estrogen receptor
      positive (ER+) breast cancer growth and interfere with the antitumor activity of
      tamoxifen at low levels. Given current knowledge, women who have ER+ tumors
      should not increase their phytoestrogen intake. Several studies suggest an
      inhibitory effect on ER- breast cancer cell growth, and it may be reasonable for
      women with ER- tumors to safely consume soy and possibly other phytoestrogens.
      However, the optimal amount and source are not clear. More research is needed to
      clarify the role of phytoestrogens in breast cancer prevention and in treating
      estrogen-deficient diseases in women who have had breast cancer.

PMID- 14583104
TI  - Herbal product use and menopause symptom relief in primary care patients: a
      MetroNet study.
AB  - OBJECTIVES: The four study objectives were to determine (1) the prevalence of use
      of four herbal product types promoted to reduce menopause symptoms
      (phytoestrogens, St. John's wort, Ginkgo biloba, and ginseng) among primary care
      patients approaching or in menopause, (2) the extent to which women who use these
      types of herbal products report menopause-related symptoms compared with herbal
      product nonusers, (3) the frequency of reported symptom reduction after use, and
      (4) if use was disclosed to their physicians. METHODS: A cross-section of
      ethnically diverse women 40-55 years of age (35.5% African American, 60.2%
      Caucasian) who were recruited from eight primary care centers in Michigan to
      complete a self-report survey. The questionnaire included demographic items,
      health history, recent use of four herbal product types purported to relieve
      menopause symptoms and perception of symptom improvement, and interest in
      additional herbal product information. RESULTS: Of 397 women, 24.9% reported
      taking, in the previous 6 months, at least one of the four study herbs. Herbal
      product use did not vary by patient demographics or health characteristics.
      Herbal product users reported more menopause symptoms than nonusers, and 68% of
      the users said that the herbs improved their symptoms; 56.4% said that their
      physician was aware of their herbal product use. CONCLUSIONS: Primary care
      patients experiencing common menopausal symptoms are likely to use herbal
      products that are purported to provide menopause symptom relief, and many believe
      that these products improve their menopausal symptoms. Healthcare providers
      should be aware of patient's positive attitude, use patterns, and lack of
      disclosure of use of herbal medicines. Inquiry of herbal product use is another
      way for physicians to learn about patient self-medication of bothersome symptoms.

PMID- 14583105
TI  - Effects of nutrient and food intake on calcaneous bone mass among healthy
      Japanese women in the predelivery and postpartum periods.
AB  - OBJECTIVE: To clarify the dietary factors affecting change in calcaneous bone
      mass during the predelivery and postpartum periods in healthy Japanese women.
      METHODS: The calcaneous bone mass was measured as the osteo sono-assessment index
      (OSI) using the quantitative ultrasound method in 76 Japanese women who were
      pregnant between February and June 2000. These women subsequently experienced
      normal pregnancy and labor and could be followed until the sixth month after
      delivery at an obstetrics and gynecology clinic center located in metropolitan
      Tokyo. After the intraindividual changes in the OSI during the follow-up period
      were determined, the relationship between the OSI or OSI change from gestation to
      the postpartum period and the estimates of nutrient and food intake obtained
      using a 140-item semiquantitative food frequency questionnaire (FFQ) were
      analyzed using stepwise multiple regression analysis. RESULTS: Iron intake in
      gestation was a significant positive correlate with the percentage change in the
      OSI between week 36 of gestation and day 5 after delivery (p < 0.001) and that
      between week 36 of gestation and month 6 after delivery (p < 0.001) (partial
      regression coefficient of energy-adjusted iron intake, beta = 0.493 mg/day and
      0.342 mg/day, respectively). Intake of vitamin D and fruits and vegetables during
      gestation and/or postpartum was positively associated with the OSI change from
      week 36 of gestation to the postdelivery stage, whereas the OSI change was
      inversely related to the intake of carotene, sodium chloride, and meat in the
      gestation or postpartum period. CONCLUSIONS: Sufficient intake of iron, vitamin
      D, or fruits and vegetables may be important for the preservation of bone mass
      after delivery.

PMID- 14583106
TI  - The acceptability of an investigational vaginal microbicide, PRO 2000 Gel, among
      women in a phase I clinical trial.
AB  - PURPOSE: Vaginal microbicides will provide a woman-initiated prevention strategy
      that could substantially reduce rates of HIV infection. The acceptability of
      microbicides will greatly influence the use and, hence, effectiveness of such
      products. In this study, the acceptability of an investigational microbicide, PRO
      2000 Gel (Indevus Pharmaceuticals, Inc., Lexington, MA), was assessed, and
      women's opinions about microbicides and their potential for real world use were
      gathered. METHODS: Quantitative and qualitative data were collected from 30 U.S.
      and 33 South African women. All sexually active HIV-uninfected women and all
      sexually abstinent HIV-infected women participating in this phase I clinical
      trial stated in a survey that they would use PRO 2000 Gel if they had reason to
      be concerned about HIV and the product were available. Qualitative data, however,
      provided insight into the nuances of acceptability ratings. Women rated product
      safety, ease of use, and positive effects on sexual pleasure among the most
      important characteristics of acceptable microbicides. RESULTS: Opinions regarding
      product leakage, contraceptive capability, and the ability to be used without
      partners noticing, as well as characteristics of the product itself, varied
      substantially based on the context of sex and perceptions of risk within each
      individual woman's life. CONCLUSIONS: As microbicide development continues and
      the first investigational products move into efficacy trials, the needs and
      preferences of those women who constitute the potential users of microbicides
      become paramount. Providing woman-initiated microbicides that are safe, easy to
      use, and pleasurable will be key to the impact these products will have on the
      AIDS epidemic worldwide.

PMID- 14583107
TI  - Prehospital cardiac arrest and the adverse effect of male gender, but not age, on
      outcome.
AB  - OBJECTIVE: To analyze the incidence and outcome of prehospital cardiac arrest as
      it correlated to gender and age as a secondary end point in an interventional
      clinical trial. METHODS: This prospective, randomized, double-blinded clinical
      intervention trial enrolled 874 prehospital cardiopulmonary arrest patients
      encountered by prehospital urban, suburban, and rural regional emergency medical
      service (EMS) areas. This trial evaluated outcome and profiled demographic
      predictors of cardiac arrest patients refractory to defibrillation with
      intravenous access who underwent standard advanced cardiac life support (ACLS)
      intervention and empiric early administration of bicarbonate. Survival was
      measured to the emergency department (ED), and data analysis used chi-square with
      Pearson correlation. RESULTS: The overall survival rate was 14.2%. There was no
      age correlate to survival, with an average age of 67.4 for both groups. Male
      patients had a 2.4-fold increased incidence (70.7 vs. 29.3%, p = 0.001) of
      arrest, which was associated with a 60% increase in mortality (19.6% vs. 11.8, p
      = 0.004) compared with women. The risk of unfavorable outcome was increased for
      men (OR 1.826, 95% CI 1.182-2.821; RR 1.097, 95% CI 1.025-1.180) on univariate
      analysis. There appeared to be no intergroup differences found with other
      historical variables, such as the presence of myocardial infarction (MI),
      hypertension (HTN), diabetes mellitus (DM), congestive heart failure (CHF), and
      chronic obstructive pulmonary disease (COPD), which were analyzed. However, HTN
      was found more commonly (2.2 times) in men (69.1 vs. 30.9%) than in women but did
      not correlate with survival. CONCLUSIONS: Male gender, but not age, is associated
      with both an increased incidence and a worsened outcome in prehospital cardiac
      arrest.

PMID- 14583108
TI  - Patient satisfaction for homeless women.
AB  - BACKGROUND: Patient satisfaction is a key quality of care indicator for which
      little is known for the homeless women population. We hypothesized that homeless
      women who last visited homeless-focused healthcare sites (shelter/outreach
      clinics and mobile vans) will have higher satisfaction ratings than homeless
      women who last visited county/government clinics. This association was also
      tested using the Gelberg-Andersen Behavioral Model for Vulnerable Populations.
      METHODS: Data were gathered on 974 homeless women aged 15-44 in a probability
      cluster sample of 60 shelters and 18 meal programs in Los Angeles County. The
      homeless women participated in 45-minute interviews. RESULTS: Our hypothesis was
      partially supported, as shelter and outreach clinics were positively and
      significantly associated with greater quality satisfaction (beta = 10.2, p <
      0.001). Healthcare at private doctors' offices was also associated with quality,
      access, and appointment satisfaction when compared with care received at
      county/government clinics (beta = 15.9, p < 0.001; beta = 8.6, p < 0.05; beta =
      16.3, p < 0.01). CONCLUSIONS: Policymakers should encourage healthcare sites that
      serve homeless women to improve their care by learning from shelter/outreach
      clinics and private doctors.

PMID- 14583109
TI  - Factors associated with women's decisions to seek treatment for urinary
      incontinence.
AB  - BACKGROUND: Urinary incontinence is a highly prevalent and burdensome condition
      among women. However, fewer than half of women with symptoms talk to a physician
      about incontinence, and the determinants of treatment seeking are not well
      understood. DESIGN: A two-stage cross-sectional survey of adult U.S. women;
      45,000 households participating in NFO Worldgroup survey research received a
      questionnaire to identify adults with incontinence. Based on stratified random
      sampling of identified incontinent women, 2310 women received a detailed
      questionnaire. RESULTS: Among 1970 women with urinary incontinence symptoms, 38%
      had initiated a conversation with a physician about incontinence. In multivariate
      logistic regression analysis, some of the factors associated significantly with
      treatment seeking were symptom duration >3 years (OR 2.33, 95% CI 1.57-3.45),
      having a history of a noticeable accident (OR 1.41, 95% CI 1.06-1.87), worse
      disease-specific quality of life scores (OR 1.89, 95% CI 1.32-2.70), not being
      embarrassed to talk with a physician about urinary symptoms (OR 1.65, 95% CI 1.28
      2.14), talking with others about urinary incontinence (OR 3.34, 95% CI 2.49
      4.49), and keeping regular appointments for routine/preventive care (OR 2.25, 95%
      CI 1.54-3.29). CONCLUSIONS: Less than half of community-dwelling adult U.S. women
      with symptoms of urinary incontinence have talked with a physician about urinary
      incontinence. In addition to duration of symptoms, factors associated with
      treatment seeking included the impact of incontinence on quality of life, lack of
      embarrassment about talking to a physician about urinary symptoms, and attitudes
      toward healthcare use. Concerns about the meaning of incontinence for overall and
      future health were important reasons for women choosing to seek treatment.

PMID- 14583110
TI  - Helping women with disabilities and domestic violence: strategies, limitations,
      and challenges of domestic violence programs and services.
AB  - PURPOSE: To describe the types of services provided to women with disabilities at
      community-based domestic violence programs in the state of North Carolina, the
      challenges faced, and strategies used to provide the services. METHODS: We
      conducted a statewide cross-sectional survey of community domestic violence
      programs and had a response rate of 85%. RESULTS: Of the participating programs,
      99% provided services to at least one woman with a physical or mental disability
      in the preceding 12 months; 85% offered shelter services to women with physical
      or mental disabilities. Most respondents (94%-99%) reported that their programs
      were either somewhat able or very able to provide effective services and care to
      women with disabilities. The respondents also described challenges to serving
      women with disabilities, including lack of funding, lack of training, and
      structural limitations of service facilities. Strategies used by the programs to
      overcome these challenges were networking and coordinating care with
      organizations that specifically serve disabled populations. CONCLUSIONS: Domestic
      violence programs in North Carolina provide services to women with disabilities
      but are faced with challenges stemming from limited funding, physical space, and
      training. Collaborations between domestic violence and disability service
      providers are necessary to improving the services and care delivered to women
      with disabilities who experience domestic violence.

PMID- 14583112
TI  - BioSPICE: a computational infrastructure for integrative biology.

PMID- 14583113
TI  - A software package for cDNA microarray data normalization and assessing
      confidence intervals.
AB  - DNA microarray data are affected by variations from a number of sources. Before
      these data can be used to infer biological information, the extent of these
      variations must be assessed. Here we describe an open source software package,
      lcDNA, that provides tools for filtering, normalizing, and assessing the
      statistical significance of cDNA microarray data. The program employs a
      hierarchical Bayesian model and Markov Chain Monte Carlo simulation to estimate
      gene-specific confidence intervals for each gene in a cDNA microarray data set.
      This program is designed to perform these primary analytical operations on data
      from two-channel spotted, or in situ synthesized, DNA microarrays.

PMID- 14583114
TI  - PAINT: a promoter analysis and interaction network generation tool for gene
      regulatory network identification.
AB  - We have developed a bioinformatics tool named PAINT that automates the promoter
      analysis of a given set of genes for the presence of transcription factor binding
      sites. Based on coincidence of regulatory sites, this tool produces an
      interaction matrix that represents a candidate transcriptional regulatory
      network. This tool currently consists of (1) a database of promoter sequences of
      known or predicted genes in the Ensembl annotated mouse genome database, (2)
      various modules that can retrieve and process the promoter sequences for binding
      sites of known transcription factors, and (3) modules for visualization and
      analysis of the resulting set of candidate network connections. This information
      provides a substantially pruned list of genes and transcription factors that can
      be examined in detail in further experimental studies on gene regulation. Also,
      the candidate network can be incorporated into network identification methods in
      the form of constraints on feasible structures in order to render the algorithms
      tractable for large-scale systems. The tool can also produce output in various
      formats suitable for use in external visualization and analysis software. In this
      manuscript, PAINT is demonstrated in two case studies involving analysis of
      differentially regulated genes chosen from two microarray data sets. The first
      set is from a neuroblastoma N1E-115 cell differentiation experiment, and the
      second set is from neuroblastoma N1E-115 cells at different time intervals
      following exposure to neuropeptide angiotensin II. PAINT is available for use as
      an agent in BioSPICE simulation and analysis framework (www.biospice.org), and
      can also be accessed via a WWW interface at www.dbi.tju.edu/dbi/tools/paint/.

PMID- 14583115
TI  - A sense of life: computational and experimental investigations with models of
      biochemical and evolutionary processes.
AB  - We collaborate in a research program aimed at creating a rigorous framework,
      experimental infrastructure, and computational environment for understanding,
      experimenting with, manipulating, and modifying a diverse set of fundamental
      biological processes at multiple scales and spatio-temporal modes. The novelty of
      our research is based on an approach that (i) requires coevolution of
      experimental science and theoretical techniques and (ii) exploits a certain
      universality in biology guided by a parsimonious model of evolutionary mechanisms
      operating at the genomic level and manifesting at the proteomic, transcriptomic,
      phylogenic, and other higher levels. Our current program in "systems biology"
      endeavors to marry large-scale biological experiments with the tools to ponder
      and reason about large, complex, and subtle natural systems. To achieve this
      ambitious goal, ideas and concepts are combined from many different fields:
      biological experimentation, applied mathematical modeling, computational
      reasoning schemes, and large-scale numerical and symbolic simulations. From a
      biological viewpoint, the basic issues are many: (i) understanding common and
      shared structural motifs among biological processes; (ii) modeling biological
      noise due to interactions among a small number of key molecules or loss of
      synchrony; (iii) explaining the robustness of these systems in spite of such
      noise; and (iv) cataloging multistatic behavior and adaptation exhibited by many
      biological processes.

PMID- 14583116
TI  - The Karyote physico-chemical genomic, proteomic, metabolic cell modeling system.
AB  - Modeling approaches to the dynamics of a living cell are presented that are
      strongly based on its underlying physical and chemical processes and its
      hierarchical spatio-temporal organization. Through the inclusion of a broad
      spectrum of processes and a rigorous analysis of the multiple scale nature of
      cellular dynamics, we are attempting to advance cell modeling and its
      applications. The presentation focuses on our cell modeling system, which
      integrates data archiving and quantitative physico-chemical modeling and
      information theory to provide a seamless approach to the modeling/data analysis
      endeavor. Thereby the rapidly growing mess of genomic, proteomic, metabolic, and
      cell physiological data can be automatically used to develop and calibrate a
      predictive cell model. The discussion focuses on the Karyote cell modeling system
      and an introduction to the CellX and VirusX models. The Karyote software system
      integrates three elements: (1) a model-building and data archiving module that
      allows one to define a cell type to be modeled through its reaction network,
      structure, and transport processes as well as to choose the surrounding medium
      and other parameters of the phenomenon to be modeled; (2) a genomic, proteomic,
      metabolic cell simulator that solves the equations of metabolic reaction,
      transcription/translation polymerization and the exchange of molecules between
      parts of the cell and with the surrounding medium; and (3) an information theory
      module (ITM) that automates model calibration and development, and integrates a
      variety of data types with the cell dynamic computations. In Karyote, reactions
      may be fast (equilibrated) or slow (finite rate), and the special effects of
      enzymes and other minority species yielding steady-state cycles of arbitrary
      complexities are accounted for. These features of the dynamics are handled via
      rigorous multiple scale analysis. A user interface allows for an automated
      generation and solution of the equations of multiple timescale, compartmented
      dynamics. Karyote is based on a fixed intracellular structure. However, cell
      response to changes in the host medium, damage, development or transformation to
      abnormality can involve dramatic changes in intracellular structure. As this
      changes the nature of the cellular dynamics, a new model, CellX, is being
      developed based on the spatial distribution of concentration and other variables.
      This allows CellX to capture the self-organizing character of cellular behavior.
      The self-assembly of organelles, viruses, and other subcellular bodies is being
      addressed in a second new model, VirusX, that integrates molecular mechanics and
      continuum theory. VirusX is designed to study the influence of a host medium on
      viral self-assembly, structural stability, infection of a single cell, and
      transmission of disease.

PMID- 14583117
TI  - Modeling regulatory networks at Virginia Tech.
AB  - The life of a cell is governed by the physicochemical properties of a complex
      network of interacting macromolecules (primarily genes and proteins). Hence, a
      full scientific understanding of and rational engineering approach to cell
      physiology require accurate mathematical models of the spatial and temporal
      dynamics of these macromolecular assemblies, especially the networks involved in
      integrating signals and regulating cellular responses. The Virginia Tech
      Consortium is involved in three specific goals of DARPA's computational biology
      program (Bio-COMP): to create effective software tools for modeling gene-protein
      metabolite networks, to employ these tools in creating a new generation of
      realistic models, and to test and refine these models by well-conceived
      experimental studies. The special emphasis of this group is to understand the
      mechanisms of cell cycle control in eukaryotes (yeast cells and frog eggs). The
      software tools developed at Virginia Tech are designed to meet general
      requirements of modeling regulatory networks and are collected in a problem
      solving environment called JigCell.

PMID- 14583118
TI  - From annotated genomes to metabolic flux models and kinetic parameter fitting.
AB  - Significant advances in system-level modeling of cellular behavior can be
      achieved based on constraints derived from genomic information and on optimality
      hypotheses. For steady-state models of metabolic networks, mass conservation and
      reaction stoichiometry impose linear constraints on metabolic fluxes. Different
      objectives, such as maximization of growth rate or minimization of flux distance
      from a reference state, can be tested in different organisms and conditions. In
      particular, we have suggested that the metabolic properties of mutant bacterial
      strains are best described by an algorithm that performs a minimization of
      metabolic adjustment (MOMA) upon gene deletion. The increasing availability of
      many annotated genomes paves the way for a systematic application of these flux
      balance methods to a large variety of organisms. However, such a high throughput
      goal crucially depends on our capacity to build metabolic flux models in a fully
      automated fashion. Here we describe a pipeline for generating models from
      annotated genomes and discuss the current obstacles to full automation. In
      addition, we propose a framework for the integration of flux modeling results and
      high throughput proteomic data, which can potentially help in the inference of
      whole-cell kinetic parameters.

PMID- 14583119
TI  - Analysis of noise in quorum sensing.
AB  - Noise may play a pivotal role in gene circuit functionality, as demonstrated for
      the genetic switch in the bacterial phage lambda. Like the lambda switch,
      bacterial quorum sensing (QS) systems operate within a population and contain a
      bistable switching element, making it likely that noise plays a functional role
      in QS circuit operation. Therefore, a detailed analysis of the noise behavior of
      QS systems is needed. We have developed a set of tools generally applicable to
      the analysis of gene circuits, with an emphasis on investigations in the
      frequency domain (FD), that we apply here to the QS system in the marine
      bacterium Vibrio fischeri. We demonstrate that a tight coupling between exact
      stochastic simulation and FD analysis provides insights into the
      structure/function relationships in the QS circuit. Furthermore, we argue that a
      noise analysis is incomplete without consideration of the power spectral
      densities (PSDs) of the important molecular output signals. As an example we
      consider reversible reactions in the QS circuit, and show through analysis and
      exact stochastic simulation that these circuits make significant and dynamic
      modifications to the noise spectra. In particular, we demonstrate a "whitening"
      effect, which occurs as the noise is processed through these reversible
      reactions.

PMID- 14583121
TI  - Preliminary research on the efficacy of virtual reality exposure therapy to treat
      driving phobia.
AB  - This article presents a review of preliminary research of two studies of the
      efficacy of virtual reality exposure therapy (VRET) to treat driving phobia.
      Study 1 describes a case study of a patient who completed a 7-day baseline
      followed by three sessions of VRET. Her peak anxiety decreased within and across
      sessions. At the post-treatment assessment, her phobic-related symptoms had
      diminished and she no longer met diagnostic criteria for driving phobia. Clinical
      improvement was maintained at 1-, 3-, and 7-month follow-up. In study 2, a
      multiple baseline across-subjects design was used to treat five patients over
      eight weekly VRET sessions. Visual and statistical analyses showed clear
      improvement in driving anxiety and avoidance in three patients between pre- and
      post-treatment assessments, and they no longer met criteria for driving phobia.
      There was marginal improvement in one patient, and the remaining individual
      showed no treatment gains. There was negligible change in actual driving
      frequency for any of the patients. Some gains were lost at the follow-up,
      particularly for the two individuals with poorer treatment responses. The results
      from these preliminary studies suggest that VRET may be a promising intervention
      for treating driving phobia. Avenues for improving treatment outcome are
      discussed.

PMID- 14583122
TI  - Anxiety and presence during VR immersion: a comparative study of the reactions of
      phobic and non-phobic participants in therapeutic virtual environments derived
      from computer games.
AB  - Virtual reality can be used to provide phobic clients with therapeutic exposure
      to phobogenic stimuli. However, purpose-built therapeutic VR hardware and
      software can be expensive and difficult to adapt to individual client needs. In
      this study, inexpensive and readily adaptable PC computer games were used to
      provide exposure therapy to 13 phobic participants and 13 non-phobic control
      participants. It was found that anxiety could be induced in phobic participants
      by exposing them to phobogenic stimuli in therapeutic virtual environments
      derived from computer games (TVEDG). Assessments were made of the impact of
      simulator sickness and of sense of presence on the phobogenic effectiveness of
      TVEDGs. Participants reported low levels of simulator sickness, and the results
      indicate that simulator sickness had no significant impact on either anxiety or
      sense of presence. Group differences, correlations, and regression analyses
      indicate a synergistic relationship between presence and anxiety. These results
      do not support Slater's contention that presence and emotion are orthogonal.

PMID- 14583124
TI  - Spatial navigation in virtual reality environments: an EEG analysis.
AB  - Past research has linked theta oscillations (electroencephalographic activity in
      the 4-8-Hz range) to spatial navigation in rodents and humans, and to the
      encoding and retrieval of spatial information in rodents. In the present study,
      electroencephalographic activity was measured while humans navigated through
      virtual mazes. Results confirmed previous findings that the frequency of theta
      episodes is directly related to the difficulty of maze navigation. We were also
      able to show that theta episodes occur most likely at points in a maze where new
      hallways come into view, or after navigational mistakes have been realized and
      are being corrected. This indicates that, just as in rodents, theta episodes in
      humans are related to the encoding and retrieval of spatial information.

PMID- 14583123
TI  - The effect of two types of virtual reality on voluntary center of pressure
      displacement.
AB  - Voluntary movements result in internal perturbations of balance and equilibrium.
      One variable regulated during movement is the position of the center of pressure
      (COP). Sensory information from the visual, vestibular and somatosensory systems
      is used in establishing relevant frames of reference for postural control. In
      this study, we were interested in determining whether different limitations of
      COP movement occur when different approaches to delivering virtual environments
      are used and when visual information incoherent with vestibular and somatosensory
      information is provided. Eighteen healthy adults completed voluntary lateral
      reaches under three conditions: continuous lateral reach (CLR), flatscreen
      virtual reality (FS), and head-mounted display virtual reality (HMD). Reaching
      behavior was indexed by force plate measures of maximum anterior-posterior and
      lateral displacement of the COP. The COP movement decreased in the lateral
      direction in the HMD condition relative to the FS. The maximum range of COP
      movement in the anterior-posterior direction increased as a function of reaching
      task with HMD realizing the greatest amount of movement. The lack of an
      exocentric frame of reference in HMD coherent with information from other sensory
      systems results in limiting COP movement within the base of support (BOS) in
      order to decrease the challenge to the postural control system.

PMID- 14583125
TI  - A data glove with tactile feedback for FMRI of virtual reality experiments.
AB  - Virtual reality (VR) technology is increasingly recognized as a useful tool for
      the assessment and rehabilitation of neurologic and psychiatric disorders. The
      hope that VR can accurately mimic real-life events is also of great interest in
      basic neuroscience, to identify the brain activity that underlies complex
      behavior by combining VR with techniques such as functional magnetic resonance
      imaging (fMRI). Toward these applications, in this study we designed and
      validated an fMRI-compatible data glove with a built-in vibratory stimulus device
      for tactile feedback during VR experiments. A simple VR-fMRI experiment was
      performed at 3.0 Tesla on four young healthy adults involving touching a virtual
      object with and without tactile feedback. The usefulness of the data glove was
      subsequently assessed using a series of questionnaires, behavioral performance,
      and the resulting activation images. Questionnaire scores indicated positive
      opinions with respect to the data glove, the tactile feedback, and the
      experimental paradigm. All subjects felt comfortable in the scanner during the VR
      experiment and were able to perform all aspects of the tasks successfully and
      with reasonable accuracy. In addition, activation maps showed the anticipated
      modulations in motor, somatosensory, and parietal cortex. These results support
      that tactile feedback enhances the realism of virtual hand-object interactions,
      and that the tactile data glove is suitable for use in other VR-fMRI research
      applications (e.g., VR physical therapy for stroke recovery).

PMID- 14583126
TI  - Multisensory integration in speed estimation during self-motion.
AB  - This study assessed the relative contributions of visual and proprioceptive/motor
      information during self-motion in a virtual environment using a speed
      discrimination task. Subjects wore a head-mounted display and rode a stationary
      bicycle along a straight path in an empty, seemingly infinite hallway with random
      surface texture. For each trial, subjects were required to pedal the bicycle
      along two paths at two different speeds (a standard speed and a comparison speed)
      and subsequently report whether the second speed travelled was faster than the
      first. The standard speed remained the same while the comparison speed was varied
      between trials according to the method of constant stimuli. When visual and
      proprioceptive/motor cues were provided separately or in combination, the speed
      discrimination thresholds were comparable, suggesting that either cue alone is
      sufficient. When the relation between visual and proprioceptive information was
      made inconsistent by varying optic flow gain, the resulting psychometric
      functions shifted along the horizontal axis (pedalling speed). The degree of
      separation between these functions indicated that both optic flow and
      proprioceptive cues contributed to speed estimation, with proprioceptive cues
      being dominant. These results suggest an important role for proprioceptive
      information in speed estimation during self-motion.

PMID- 14583127
TI  - Eye-tracking in immersive environments: a general methodology to analyze
      affordance-based interactions from oculomotor dynamics.
AB  - This paper aims at presenting a new methodology to study how perceptual and motor
      processes organized themselves in order to achieve invariant visual information
      picking-up in virtual immersions. From a head-mounted display, head and eye
      movements were recorded using tracking devices (magnetic and infrared) that
      render the six degrees-of-freedom associated with the position and orientation of
      head movements, and two degrees-of-freedom from one eye. We measured the
      continuous line of sight's deviation from a pre-selected area on a virtual
      stimulus. Some preliminary analyses of the dynamical properties of the emergent
      perceptual and motor patterns are presented as they are considered to be
      representative of the process of affordance extraction.

PMID- 14583128
TI  - Cyberpsychology: a human-interaction perspective based on cognitive modeling.
AB  - This paper argues for the relevance of cognitive modeling and cognitive
      architectures to cyberpsychology. From a human-computer interaction point of
      view, cognitive modeling can have benefits both for theory and model building,
      and for the design and evaluation of sociotechnical systems usability. Cognitive
      modeling research applied to human-computer interaction has two complimentary
      objectives: (1) to develop theories and computational models of human interactive
      behavior with information and collaborative technologies, and (2) to use the
      computational models as building blocks for the design, implementation, and
      evaluation of interactive technologies. From the perspective of building theories
      and models, cognitive modeling offers the possibility to anchor cyberpsychology
      theories and models into cognitive architectures. From the perspective of the
      design and evaluation of socio-technical systems, cognitive models can provide
      the basis for simulated users, which can play an important role in usability
      testing. As an example of application of cognitive modeling to technology design,
      the paper presents a simulation of interactive behavior with five different
      adaptive menu algorithms: random, fixed, stacked, frequency based, and activation
      based. Results of the simulation indicate that fixed menu positions seem to offer
      the best support for classification like tasks such as filing e-mails. This
      research is part of the Human-Computer Interaction, and the Broadband Visual
      Communication research programs at the National Research Council of Canada, in
      collaboration with the Carleton Cognitive Modeling Lab at Carleton University.

PMID- 14583129
TI  - Capturing behaviour for the use of avatars in virtual environments.
AB  - Avatars, representations of people in virtual environments, are subject to human
      control. However, for most applications, it is impractical for a person to
      directly control each joint in a complex avatar. Rather, people must be allowed
      to specify complex behaviours with simple instructions and the avatar permitted
      to select the correct movements in sequence to execute the instruction. This
      requires a variety of technologies that are currently available. Human behaviour
      must be captured and stored it so that it can be retrieved at a later time for
      use by the avatar. This has been done successfully with a variety of haptic
      interfaces, with visual observation of human head movements, and with verbal
      behaviour in natural language applications. The behaviour must be broken into
      atomic actions that can be sequenced with a regular grammar, and an appropriate
      grammar developed. Finally, a user interface must be developed so that a person
      can deliver instructions to the avatar.

PMID- 14583130
TI  - Using VR to improve the performance of low-earth orbit space robot operations.
AB  - The operations of current robotics systems in low-earth orbit could benefit from
      the use of virtual reality (VR) systems to improve their performance. This paper
      presents an example of the type of contribution such a system could provide to
      assist the space robot operators in their operations, by using the increased
      situational awareness and the ease of use associated with VR systems.

PMID- 14583131
TI  - Project EMMA: Engaging Media for Mental Health Applications.

PMID- 14583132
TI  - Effects of brinzolamide on aqueous humor dynamics in monkeys and rabbits.
AB  - This study examines the mechanisms by which brinzolamide reduces intraocular
      pressure (IOP) in healthy rabbits and in monkeys with unilateral ocular
      hypertension. Intraocular pressures were measured by pneumatonometry and aqueous
      flow was determined by fluorophotometry before and after three twice-daily drops
      of 1% brinzolamide to both eyes per monkey and after similar treatment to one eye
      per rabbit. In monkeys, outflow facility was determined by fluorophotometry and
      uveoscleral outflow was calculated. In rabbits, outflow facility was determined
      by two-level constant pressure infusion and uveoscleral outflow was measured by
      an intracameral tracer technique. Compared with contralateral vehicle-treated
      rabbit eyes, IOP was reduced in brinzolamide-treated eyes by 2.5 +/- 1.9 mmHg
      (mean +/- standard deviation; p =.006) at four hours after the second dose.
      Aqueous flow was reduced by 0.50 +/- 0.65 microl/min (p =.02). This effect was
      found in rabbits previously treated with brinzolamide but not in naive rabbits.
      Treated hypertensive eyes of monkeys had a reduction in IOP of 7.3 +/- 8.8 mmHg
      (p = 0.01) and aqueous flow of 0.69 +/- 1.10 microL/min (p = 0.05) when compared
      with baseline. Brinzolamide did not affect outflow facility or uveoscleral
      outflow in either rabbits or monkeys. It is concluded that, in normotensive eyes
      of rabbits and hypertensive eyes of monkeys, brinzolamide reduces IOP by reducing
      aqueous flow and not by affecting aqueous humor drainage.

PMID- 14583133
TI  - Intraocular pressure, safety, and quality of life in glaucoma patients switching
      to latanoprost from monotherapy treatments.
AB  - PURPOSE: To evaluate the efficacy, safety and quality of life in ocular
      hypertensive or open-angle glaucoma patients who required alteration in previous
      therapy and were changed to latanoprost. METHODS: A prospective, multicenter,
      active, historical controlled trial in which qualified patients had previous
      therapy substituted with latanoprost 0.005% and were followed for up to 6 months.
      RESULTS: 3179 patients were included in the intent-to-treat analysis. In all
      patients latanoprost reduced the intraocular pressure (IOP) from 20.1 +/- 3.9 to
      17.1 +/- 3.5 mm Hg (p< 0.0001) and when compared to previous monotherapies: beta
      blockers (-3.0 +/- 3.5, n = 1976), alpha-agonists (-3.6 +/- 3.7, n = 581),
      miotics (-2.8 +/- 3.0, n = 21), carbonic anhydrase inhibitors (-3.2 +/- 3.5, n =
      198), and other prostaglandin analogs (-1.6 +/- 3.7, n = 402). The most common
      ocular adverse event with latanoprost was conjunctival hyperemia (n = 66, 2.0%
      incidence) and the most common systemic adverse event was headache (n = 9, 0.2%).
      Over the 6-month treatment interval 89.8% of patients were maintained on
      latanoprost. On the solicited symptom survey patients showed a preference for
      latanoprost compared to previous therapy for several reasons: (depending on the
      product) dryness, blurred vision, tearing, stinging on instillation, crusting,
      itching, fatigue, dizziness, despondency and dry mouth (p < 0.005). CONCLUSION:
      Latanoprost generally provides reduced IOP, limited side-effects, improvement in
      many quality of life measures and is maintained in patients who required a
      substitution from previous monotherapy.

PMID- 14583134
TI  - A six-week, parallel, randomized, double-blind study comparing the efficacy and
      safety of the 0.5% timolol/2.0% MK-507 combination b.i.d. to the concomitant
      administration of 0.5% timolol b.i.d. and 2.0% MK-507 b.i.d.
AB  - This was a 6-week, parallel, randomized, double-blind study comparing the
      efficacy and safety of the 0.5% timolol/2.0% MK-507 combination b.i.d. to the
      concomitant administration of 0.5% timolol b.i.d. and 2.0% MK-507 b.i.d. Patients
      with ocular hypertension or open-angle glaucoma from 21 to 85 years of age were
      enrolled in this study. Each of them should have intraocular pressure (IOP) of 20
      mmHg or more in the study eye after they completed the wash-out period. The
      patients enrolled were randomly assigned to either combination (0.5% timolol/2.0%
      MK-507 b.i.d. and placebo b.i.d.) or concomitant (0.5% timolol b.i.d. and 2.0% MK
      507 b.i.d.) treatment. During the study, no systemic or topical medication
      affecting IOP other than test drugs were allowed. A total of 20 randomized
      patients were included in the intention-to-treat population for analysis of data.
      The ten were assigned to the combination treatment and others were assigned to
      the concomitant treatment. There was no statistically significant difference
      between the two study treatments in terms of gender distribution, average age,
      and average IOP at the trough and the peak before starting the test medications.
      Mean reduction of the IOP from baseline to the final visit at the trough was 5.04
      mmHg in the combination treatment and was 2.73 mmHg in the concomitant treatment.
      Mean reduction of the IOP at the peak was 2.19 mmHg in the combination treatment
      and was 2.53 mmHg in the concomitant treatment. There were no statistically
      significant differences in the above analyses between the two treatments. Safety
      evaluation was carried out, and number of adverse events in each treatment group
      did not differ substantially. Ocular signs and symptoms were evaluated in each
      visit, and all of the between-treatment values were not different significantly,
      either. Laboratory tests were performed, and showed no significant differences
      between pre- and post-treatment periods. None of these was found to be clinically
      serious, either. We concluded that the 0.5% timolol/2.0% MK-507 combination
      b.i.d. is equivalent in the efficacy of lowering IOP as well as safety compared
      to the concomitant administration of 0.5% timolol b.i.d. and 2.0% MK-507 b.i.d.
      in patients with ocular hypertension or open-angle glaucoma.

PMID- 14583135
TI  - CNP-induced changes in pHi, cGMP/cAMP and mRNA expression of natriuretic peptide
      receptors in human trabecular meshwork cells.
AB  - It has been demonstrated that natriuretic peptides lower intraocular pressure,
      however, the underlying cellular mechanism(s) mediating this response remain(s)
      to be determined. The purpose of this study was to investigate the effects of C
      type natriuretic peptide (CNP) on pH(i), cGMP/cAMP and expression of atrial
      natriuretic peptide receptor (NPR-A), brain natriuretic peptide receptor (NPR-B)
      and C-type natriuretic peptide receptor (NPR-C), in HTM cells. At concentrations
      of 10(-7) M, CNP caused an acidification of pH(i). In addition, CNP caused a dose
      dependent increase in cGMP formation and inhibition of forskolin-stimulated cAMP
      accumulation. These changes were not significantly altered in the absence of 10(
      3) M isobutylmethylxanthine (IBMX). Treatment with the NPR-A antagonist, anantin,
      produced no influence on basal cGMP/cAMP levels, the CNP-stimulated cGMP
      accumulation and CNP-induced inhibition of forskolin-stimulated cAMP
      accumulation. However, CNP-induced reduction of forskolin-stimulated cAMP
      accumulation was inhibited by pretreatment with pertussis toxin (PTX).
      Furthermore, NPRB receptors were predominantly expressed and pretreatment with
      CNP (10(-7) M, 24hr) enhanced all NPR mRNAs expression which was not altered by
      higher concentrations or longer incubation. Results demonstrate that NPR-A, NPR-B
      and NPR-C receptors' expression can be up-regulated by CNP treatment. CNP
      activates NPR-B receptors preferentially to increase cGMP accumulation and acts
      through the PTX-sensitive cAMP-signaling pathway leading to a decrease in pH(i).

PMID- 14583136
TI  - Human ciliary muscle cell responses to FP-class prostaglandin analogs:
      phosphoinositide hydrolysis, intracellular Ca2+ mobilization and MAP kinase
      activation.
AB  - Phospholipase C induced phosphoinositide (PI) turnover, intracellular Ca(2+)
      ([Ca(2+)](i)) mobilization and mitogen-activated protein (MAP) kinase activation
      by FP-class prostaglandin analogs was studied in normal human ciliary muscle (h
      CM) cells. Agonist potencies obtained in the PI turnover assays were: travoprost
      acid ((+)-fluprostenol; EC(50) = 2.6 +/- 0.8 nM) > bimatoprost acid (EC(50) = 3.6
      +/- 1.2 nM) > (+/-)-fluprostenol (EC(50) = 4.3 +/- 1.3 nM) >> prostaglandin F(2
      alpha) (PGF(2 alpha)) (EC(50) = 134 +/- 17 nM) > latanoprost acid (EC(50) = 198
      +/- 83 nM) > S-1033 (EC(50) = 2930 +/- 1420 nM) > unoprostone (EC(50) = 5590 +/-
      1490 nM) > bimatoprost (EC(50) = 9600 +/- 1100 nM). Agonist potencies in h-CM
      cells correlated well with those previously obtained for the cloned human ciliary
      body-derived FP receptor (r = 0.96, p< 0.001) and that present on h-TM cells (r =
      0.94, p< 0.0001). Travoprost acid, PGF(2 alpha) and unoprostone also stimulated
      [Ca(2+)](i) mobilization in h-CM cells with travoprost acid being the most potent
      agonist. MAP kinase activity was stimulated in the h-CM cells with the following
      rank order of activity (at 100 nM): travoprost acid > PGF(2 alpha) > latanoprost
      acid > PGD(2) > bimatoprost > latanoprost = bimatoprost acid = fluprostenol >
      PGE(2) = S-1033 > unoprostone > PGI(2). The PI turnover, [Ca(2+)](i) mobilization
      and MAP kinase activation induced by several of these agonists was blocked by the
      FP receptor antagonist, AL-8810 (11 beta-fluoro-15-epiindanyl PGF(2 alpha)) (e.g.
      K(i) = 5.7 microM versus PI turnover). These studies have characterized the
      biochemical and pharmacological properties of the native FP prostaglandin
      receptor present on h-CM cells using three signal transduction mechanism assays
      and a broad panel of FP-class agonist analogs (including free acids of
      bimatoprost, travoprost and latanoprost) and the FP receptor antagonist, AL-8810.

PMID- 14583137
TI  - Genistein suppressed upregulation of vascular endothelial growth factor
      expression by cobalt chloride and hypoxia in rabbit retinal pigment epithelium
      cells.
AB  - The time course changes of vascular endothelial growth factor (VEGF) protein
      expression induced by cobalt chloride (CoCl(2)) and hypoxia and the effects of
      genistein on CoCl(2)- and hypoxia-induced VEGF expression in rabbit retinal
      pigment epithelium (RPE) cells were studied. Judged by relative fluorescence
      using a confocal scanning laser microscope coupled to a computer, VEGF protein
      expression exposed for different periods to CoCl(2) or hypoxia was investigated.
      CoCl(2) was found to significantly elevate VEGF protein expression. At 4 h after
      CoCl(2) treatment, the expression of VEGF protein was about three times as much
      as that at the start of treatment. Genistein (50, 100 and 200 microM) inhibited
      VEGF protein expression elicited by CoCl(2) in a concentration-dependent manner.
      Hypoxia (5% CO(2)/95% N(2)) could markedly increase VEGF protein expression. The
      elevation of VEGF protein expression was gradual and time-dependently. At 6 h,
      the highest expression of VEGF protein was observed, it was about three times as
      much as that at the start of treatment. After preincubation with 50, 100, and 200
      microM genistein respectively, the hypoxia-evoked VEGF expression was
      concentration-dependently suppressed. These results indicated that genistein
      could be an effective agent in the prevention and treatment of intraretinal and
      subretinal neovascularization.

PMID- 14583138
TI  - Regulation of Na,K-ATPase expression by endothelin-1 in transformed human ciliary
      non-pigmented epithelial (HNPE) cells.
AB  - Endothelin-1 (ET-1) (1-100 nM) decreases the activity of Na,K-ATPase, a key
      enzyme responsible for aqueous humor formation, in transformed human non
      pigmented ciliary epithelial (HNPE) cells. The present study sought to determine
      if ET-1 alters the expression of the catalytically active alpha subunit of Na,K
      ATPase in HNPE cells and identify mechanisms underlying these effects. We report
      that acute (15 and 30 min) treatment with ET-1 results in an increase in mRNA
      expression of the alpha 1 subunit of Na,K-ATPase. Similar to ET-1's effects,
      ouabain (100 microM), a selective inhibitor of Na,K-ATPase, and monensin (10
      microM), a sodium ionophore, also increased Na,K-ATPase expression in HNPE cells.
      The increase in Na,K-ATPase expression by short-term treatment with ouabain and
      monensin was dependent on their ability to elevate intracellular sodium
      concentrations. However, acute ET-1 treatment mediated increase in Na,K-ATPase
      expression was independent of changes in intracellular sodium. A prolonged (24
      hr) ET-1 treatment results in an increase in both mRNA and protein levels of the
      alpha 1 subunit of Na,K-ATPase. These observations suggest that ET-1 could play a
      homeostatic role in modulating aqueous humor formation by having differential
      effects on the activity and expression of Na,K-ATPase by the ciliary epithelium
      in the eye.

PMID- 14583139
TI  - Evaluation and prediction of fluoroquinolone pharmacodynamics in bacterial
      keratitis.
AB  - Observational studies suggest that a pharmacodynamic index helps to predict the
      therapeutic outcome of respiratory and other infections. This study explored the
      prognostic importance of a ratio of the achievable corneal level for a
      fluoroquinolone to the fluoroquinolone's minimal inhibitory concentration (MIC)
      for corneal isolates of 391 patients with bacterial keratitis. The peak
      concentration and the area under the concentration curve (AUC) in the cornea were
      estimated from reported values achieved with topical ciprofloxacin. The
      inhibitory quotient (IQ) was calculated as the ratio of the estimated peak
      achievable corneal ciprofloxacin concentration to the ciprofloxacin MIC of
      keratitis isolates, and the area under the inhibitory curve (AUIC) was defined as
      the expected 24-hour AUC divided by the MIC. The probability of clinical
      improvement of ciprofloxacin-treated bacterial keratitis was 90% or more if
      ciprofloxacin's IQ was above 8 or the AUIC was greater than 151. A
      pharmacodynamic index relating corneal pharmacokinetic and susceptibility
      concentrations may correlate with the clinical response of bacterial keratitis to
      fluoroquinolone therapy.

PMID- 14583141
TI  - A survival game of hide and seek: cytomegaloviruses and MHC class I antigen
      presentation pathways.
AB  - Cytomegaloviruses (CMV) are members of the ubiquitous family of herpesviruses,
      which escape immunological clearance and persist throughout life in the infected
      host. Cytomegaloviruses have developed numerous strategies that permit them to co
      exist with their host even as an anti-virus immune response endangers their long
      term survival. A considerable number of these strategies are aimed at MHC class I
      presentation of viral proteins to CD8+ T cells (TCD8+ ). Although the gamut of
      CMV immune evasion will be briefly examined, the primary focus of this review is
      on the host ability to counteract the strategies developed by CMV to inhibit
      antigen processing and presentation. A primary mechanism used by the immune
      system is the recognition of very early virus proteins including recognition of
      the immunomodulatory proteins themselves. We further speculate that cross
      presentation of antigen is an adaptive immune response to the inhibition of
      direct presentation. Other mechanisms, such as the evolution of pAPC subsets, may
      also allow the immune system to adapt to a variety of different infectious
      pathogens while preventing cytopathic infection of all pAPCs.

PMID- 14583142
TI  - Clinical and molecular pathogenesis of varicella virus infection.
AB  - Varicella zoster virus (VZV) is a neurotropic human herpesvirus that infects
      nearly all humans and causes chickenpox (varicella). After chickenpox, VZV
      becomes latent in cranial nerve, dorsal root, and autonomic nervous system
      ganglia along the entire neuraxis. Virus reactivation produces shingles (zoster),
      characterized by pain and rash usually restricted to 1-3 dermatomes. Zoster is
      often complicated by postherpetic neuralgia (PHN), pain that persists for months
      to years after rash resolves. Virus may also spread to the spinal cord and blood
      vessels of the brain, producing a unifocal or multifocal vasculopathy,
      particularly in immunocompromised individuals. The increased incidence of zoster
      in elderly and immunocompromised individuals appears to be due to a VZV-specific
      host immunodeficiency. PHN may reflect a chronic VZV ganglionitis, and VZV
      vasculopathy is due to productive virus infection in cerebral arteries.
      Strategies that might boost host cell-mediated immunity to VZV are discussed, as
      well as the physical state of viral nucleic acid during latency and the possible
      mechanisms by which herpesvirus latency is maintained and virus is reactivated. A
      current summary of varicella latency and pathogenesis produced by simian
      varicella virus (SVV), the counterpart of human VZV, points to the usefulness of
      a primate model of natural infection to study varicella latency, as well as the
      experimental model of intratracheal inoculation to study the effectiveness of
      antiviral agents in driving persistent varicella virus into a latent state.

PMID- 14583143
TI  - Innate and adaptive immune responses determine protection against disseminated
      infection by West Nile encephalitis virus.
AB  - WNV continues to spread throughout the Western Hemisphere as virus activity in
      insects and animals has been reported in the United States, Canada, Mexico, and
      the Caribbean islands. West Nile virus (WNV) infects the central nervous system
      and causes severe disease primarily in humans who are immunocompromised or
      elderly. In this review, we discuss the mechanisms by which the immune system
      limits dissemination of WNV infection. Recent experimental studies in animals
      suggest important roles for both the innate and the adaptive immune responses in
      controlling WNV infection. Interferons, antibody, complement components and CD8+
      T cells coordinate protection against severe infection and disease. These
      findings are analyzed in the context of recent approaches to vaccine development
      and immunotherapy against WNV.

PMID- 14583144
TI  - Upper respiratory tract immunity.
AB  - Most viral infections occur via mucosal surfaces like the respiratory,
      gastrointestinal, or genital epithelium. The mucosal immune system is an
      important component of the body's defense against such infections and
      consequently induction of mucosal, in addition to systemic immunity, might
      improve vaccine efficacy. Several orally administered vaccines, for example,
      against poliovirus and gastrointestinal bacterial infections, have been developed
      and are widely used. In contrast, to date most vaccines against respiratory
      pathogens are applied parenterally and thus do not induce significant mucosal
      immunity. For the development of effective mucosal vaccines a more profound
      understanding of the immune mechanisms operative at mucosal surfaces and of the
      interplay between different mucosal compartments is needed. Moreover, factors
      like the dose, form of application, and type of mucosal adjuvants are critical to
      the induction of effective mucosal immunity. This brief review will focus mainly
      on the nasal route and will summarize some recent findings concerning the
      function of the mucosal immune system of the upper respiratory tract.
      Furthermore, routes of cross-immunization between distinct mucosal compartments
      and how they might be relevant to vaccine development will be addressed. Finally,
      I will outline critical factors for the rational design of nasal vaccines and in
      this context highlight some recent preclinical and clinical developments in the
      field.

PMID- 14583145
TI  - Calling in the troops: regulation of inflammatory cell trafficking through innate
      cytokine/chemokine networks.
AB  - The recruitment of immune effector cells to localized sites of infection is
      crucial for the effective delivery of innate immune mechanisms. Under the
      conditions of infections with murine cytomegalovirus (MCMV), a herpesvirus with
      pathogenic potential, early immune functions are essential in the control of
      virus replication and virus-induced pathology. Our studies have demonstrated that
      the chemokine macrophage inflammatory protein-1alpha (MIP-1alpha) is critical for
      natural killer (NK) cell inflammation and delivery of interferon (IFN)-gamma to
      mediate downstream protective responses against MCMV infection in liver.
      Moreover, IFN-alpha/beta-dependent mechanisms promote MIP-1alpha production and
      subsequently the accumulation of NK cells in liver. Taken together, the studies
      highlighted in this review define a unique in vivo pathway mediated by innate
      cytokines in regulating chemokine responses that are essential in the promotion
      of NK cell inflammation for localized antiviral defense. In addition, the
      downstream consequences of these events in enhancing endogenous adaptive immune
      responses will also be discussed. Overall, the innate cytokine/chemokine networks
      that are described emphasize the emerging importance of chemokine functions for
      protective immune responses during infection with viruses.

PMID- 14583146
TI  - Cytokine profiles and long-term virus-specific antibodies following immunization
      of CBA mice with equine herpesvirus 1 and viral glycoprotein D.
AB  - Equine herpesvirus 1 (EHV-1)-specific antibody-secreting cells (ASC) isolated
      from the lung and spleen of mice at 12 months after immunization with attenuated
      EHV-1 KyA, heat-killed KyA, or recombinant viral glycoprotein D (rgD) assessed by
      ELISPOT showed a three- to fivefold increase in three immunoglobulin isotypes at
      3 days post-challenge with pathogenic EHV-1 RacL11 as compared to control mice.
      ELISPOT assays demonstrated a high frequency of cells secreting proinflammatory
      tumor necrosis factor-alpha (TNF-alpha), interferon gamma (IFN-gamma), and
      interleukin 4 (IL-4) in the lungs in response to infection with KyA or RacL11 or
      immunization with rgD. Cytokine production elicited by EHV-1 KyA or RacL11
      infection revealed similar frequencies of EHV-1-specific IFN-gamma and IL-4 spot
      forming cells in the mediastinal lymph nodes and spleen. However, KyA induced
      significantly greater amounts of IFN-gamma producing cells in the lungs than did
      RacL11. Intranasal immunization with KyA or rgD induced long-term immunity that
      provided protection against pathogenic EHV-1 challenge infection at 12 months
      post-immunization. Overall, the data indicate that immunization with infectious
      KyA or rgD induces significant levels of cytokines, virus-specific ASC in the
      lungs and spleen, and long-term virus specific B-cell responses.

PMID- 14583148
TI  - Parameters of humoral and cellular immunity following vaccination of pigs with a
      European modified-live strain of porcine reproductive and respiratory syndrome
      virus (PRRSV).
AB  - Parameters of humoral and cellular immunity were investigated in pigs
      experimentally infected with a modified-live European porcine reproductive and
      respiratory syndrome virus (PRRSV, strain DV). PRRSV was detected by real-time RT
      PCR and PRRSV-specific antibodies by a commercial ELISA test-kit, respectively.
      Interleukins IL-1alpha, IL-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor (TNF
      alpha) and interferon-gamma (IFN-gamma) as well as IL-2 receptor (IL-2R) were
      quantified at mRNA level using RT-PCR. Subpopulations of blood lymphocytes were
      assayed using flow cytometry. No significant changes neither in cytokine
      expression nor in shifts of CD4 and CD8 markers could be found, but similar curve
      diagrams concerning CD8 single positive T cells could be observed in all
      vaccinated animals with an initial decrease and an increase between post
      infection days (PIDs) 7 and 14. In the vaccination group, TNF-alpha and IL-6
      tended to be increased at PIDs 22 and 40, whereas no increase could be seen in
      IFN-gamma. When comparing the in vivo immune response to that being seen in in
      vitro experiments, similar shifts of CD4/CD8 lymphocyte subpopulations may be
      seen. Cytokine curve diagrams, however, do not reflect the in vitro findings to
      that extent.

PMID- 14583147
TI  - Induction of hepatitis C virus-specific humoral and cellular immune responses in
      mice and rhesus by artificial multiple epitopes sequence.
AB  - The investigation of antigenic epitopes in hepatitis C virus (HCV) protein
      suggests that a central sequence combined with multiple antigenic epitopes of HCV
      might be significant as a potential vaccine candidate. This artificial sequence
      of combined and modified multiple antigenic epitopic peptides (Hc-B2), containing
      three B and four T cell epitopes, was constructed and expressed in E. coli.
      Antigen analysis indicated that this peptide antigen was capable of interacting
      with anti-sera collected from hepatitis C patients infected by three genotypes of
      HCV from three different geographic areas of China, respectively. The
      immunological analysis of this peptide antigen in mice and rhesus suggested that
      its immunogenicity was effective. However, a complete evaluation of this peptide
      could not be made as an effective animal model for HCV infection (such as in the
      chimpanzee) was not available for this study.

PMID- 14583149
TI  - Direct binding of herpes simplex virus type 1 virions to complement C3.
AB  - Glycoprotein C (gC) of type 1 herpes simplex virus (HSV-1) binds the human
      complement C3 as purified proteins, or when expressed on the surface of infected
      cells. However, it is not clear whether the purified HSV virion binds directly to
      C3. In this study, direct binding of purified virions, HSV-1(KOS) or HSV-1(hrR3),
      to C3-coated plate was demonstrated by an enzyme-linked immunosorbent assay
      (ELISA). Captured virions on C3-coated plates were still infectious as determined
      by adding Vero cells to allow for infection to occur. The binding of virions to
      C3 was abolished if C3 was heat-inactivated, confirming a requirement for
      complement. In addition, the interaction was inhibited by preincubation of
      purified virions with heparin. In conclusion, a direct interaction of C3 with the
      HSV-1 virions was demonstrated.

PMID- 14583150
TI  - Interleukin-10, interleukin-12, and interferon-gamma levels in the respiratory
      tract following mycoplasma hyopneumoniae and PRRSV infection in pigs.
AB  - The cytokine profile associated with either a T helper 1 (Th1) or Th2 response in
      a porcine respiratory disease model was assessed by measuring IL-12, IL-10 and
      IFN-gamma using RT-PCR and ELISA, respectively. IL-10, IL-12, and IFN-gamma
      levels in pulmonary alveolar macrophages and bronchial lavage fluid were
      increased in pigs infected with porcine reproductive and respiratory syndrome
      virus (PRRSV), Mycoplasma hyopneumoniae, or both pathogens. At 10 days post
      infection (DPI), both IL-10 and IL-12 mRNA levels were increased in both groups
      infected with PRRSV. The IL-12 levels were increased in pigs infected with both
      pathogens and IFN-gamma protein levels were increased in pigs infected with PRRSV
      alone and only numerically increased in the dual infection. At 28 DPI, IL-12 mRNA
      levels and IL-10 protein levels were increased in all infected groups. The mRNA
      level of IL-12 remained elevated in the group infected with both pathogens at 42
      DPI. Production of IFN-gamma did not appear to be closely correlated with
      elimination of virus from the respiratory tract. However, when the virus existed
      in the lung, the local IFN-gamma production appeared to increase. Although IL-12
      mRNA levels were significantly elevated in the pigs infected with both pathogens,
      the increased protein levels of IL-12 may compromise the immune system's ability
      to clear PRRSV from the lung. This could explain the prolonged presence of PRRSV,
      IFN-gamma production and the increased pneumonia observed in the lungs of dual
      infected pigs. The increased levels of cytokines associated with both Th1 and Th2
      responses in the respiratory tract of pigs infected with PRRSV and M.
      hyopneumoniae provides valuable information on the pathogenesis of these
      diseases.

PMID- 14583152
TI  - Suppression of HIV-1 replication by HIV-1-irrelevant CD8+ cytotoxic T lymphocytes
      resulting in preservation of persistently HIV-1-infected cells in vitro.
AB  - CD8+ cells of asymptomatic HIV-1 carriers (AC) contain HIV-1-specific cytotoxic T
      lymphocytes (CTLs) but suppress HIV-1 replication in a class I major
      histocompatibility complex (MHC-I)-unrestricted manner. In order to selectively
      investigate the HIV-1-suppressive function of CTLs apart from HIV-1-specific
      cytotoxicity, HIV-1-irrelevant allo-specific CTLs were established from an HIV-1
      uninfected individual and their HIV-1-suppressive activity against autologous
      CD4+ peripheral blood mononuclear cells (PBMC) was examined. We found that these
      CTLs significantly suppressed both R5 and X4-HIV-1 replication in either acutely
      or persistently infected autologous PBMC. Although these CTLs partially killed
      HIV-1-infected PBMC through Fas ligand, CTLs still suppressed late steps of HIV-1
      replication in the presence of neutralizing antibodies to Fas ligand. HIV-1
      replication in PBMC that had been suppressed by CTLs was reversible following
      depletion of CTLs from culture, analogous to the previous observation for CD8+
      cell-depleted PBMC of AC. Induction of HIV-1 replication by CTL-depletion was
      amplified by addition of newly prepared CD4+ cells or activation with
      staphylococcal enterotoxin B. Our results indicate that CTLs can suppress HIV-1
      replication in PBMC in an antigen-nonspecific manner and preserve infected cells
      in a state capable of restarting HIV-1 replication and transmission.

PMID- 14583151
TI  - Measles virus infection of rhesus macaques affects neutrophil expression of IL-12
      and IL-10.
AB  - Cytokine production by phagocytic cells is an important component of the immune
      response to infection with a variety of pathogens. Neutrophils are phagocytic
      cells capable of expressing interleukin (IL)-12 and IL-10 in response to
      infection with parasites, fungi, and bacteria. These cytokines are postulated to
      play important roles in the immune response during measles. Neutrophils isolated
      from naive or measles virus (MV)-infected rhesus macaques expressed IL-12 and IL
      10 following in vitro stimulation with lipopolysaccharide (LPS) and interferon
      gamma (IFN-gamma). Stimulated neutrophils secreted proportionally more of the
      biologically active IL-12 heterodimer p70 and more IL-10 than similarly
      stimulated peripheral blood mononuclear cells (PBMCs). During MV infection, the
      number of IL-12 and IL-10-producing neutrophils and monocytes initially
      decreased. Subsequently, IL-12 levels were restored, and IL-10 expression rose
      above baseline in both cell types. Increased IL-10 production by neutrophils and
      monocytes during MV infection may play a role in measles-induced
      immunosuppression.

PMID- 14583153
TI  - Porcine reproductive and respiratory syndrome virus persistence in blood, spleen,
      lymph nodes, and tonsils of experimentally infected pigs depends on the level of
      CD8high T cells.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) induces a persistent
      viral infection suggesting an inefficient cellular immune response. The aim of
      the study was to evaluate the relationship between viral persistence and
      cytotoxic cells in blood, spleen, mediastinal lymph nodes (MLN) and tonsils of
      PRRSV experimentally infected pigs. Groups of four to six specific pathogen-free
      (SPF) pigs were infected with the LHVA-93-3 isolate, and blood and lymphoid
      organs were collected from 3 to 60 days post-infection (p.i.). Infectious
      particles and viral RNA were more or less rapidly eliminated in serum, spleen,
      lungs and MLN but persisted the longest in tonsils. Lymphocytes CD2+ CD4+, CD2+
      CD8high, CD2+ CD8low and NK cells populations were phenotyped and their
      reactivity to PHA and ConA were tested. Analysis of T cell subsets in blood and
      lymphoid organs indicated that the percentages of CD2+ CD8+ T cells slightly
      increased in spleen at 17 days p.i, whereas no changes were observed in CD2+ CD4+
      cells in blood or lymphoid organs. However, discrimination of CD8+ cells in
      CD8high and CD8low subsets revealed that the percentages of CD2+ CD8high cells
      increased in spleen and blood from 10 to 45 or 60 days p.i. while they
      transiently increased in MLN and decreased in tonsils. The CD8low/CD8high ratio
      increased in the blood of PRRSV-infected animals at three days p.i. due to a
      transient decrease of CD2+ CD8high cells. This same ratio decreased in the spleen
      of infected pigs from 10 to 45 days p.i. due to an increase of CD2+ CD8high
      cells. The CD2+ MIL-4+ cell subset (NK cells) was not significantly modified in
      blood or lymphoid organs. In addition, the ability of lymphoid T cells from blood
      and lymphoid organs to respond to ConA or PHA stimulation was transiently
      impaired in blood and spleen during the PRRSV persistent infection. Taken
      together, these results suggest that, in persistently infected pigs, an impaired
      CD2+ CD8high cell response in MLN and tonsils favors viral persistence in these
      organs, in contrast with the response seen in blood and spleen where viral
      elimination appears to occur sooner.

PMID- 14583154
TI  - Characterization of tick-borne encephalitis virus-specific human T lymphocyte
      responses by stimulation with structural TBEV proteins expressed in a recombinant
      baculovirus.
AB  - Very little information is available on human T cell responses following exposure
      to tick-borne encephalitis virus (TBEV) proteins, largely because the virus is a
      dangerous pathogen and relatively large amounts of purified antigen would be
      required for the functional characterization of cellular immune responses. We
      have produced recombinant TBEV proteins using the baculovirus expression system
      and tested them for their capacity to stimulate T cells in vitro. T lymphocytes
      from TBEV vaccinated individuals were characterized. The recombinant E and C
      proteins triggered CD4+ but not CD8+ cells to proliferate and to produce IFN
      gamma and IL-5. T cell responses against recombinant NS3 protein were not
      detected. T cell lines with specificity for the E protein were also established.
      These lines were CD4+ and had a TH0 cytokine production pattern. Our results
      demonstrate the utility of recombinant viral proteins to study the generation and
      characterization of TBEV specific T cell responses.

PMID- 14583156
TI  - Using the kinetic chain theory in clinical practice.

PMID- 14583155
TI  - Invasion and persistence of the neuroadapted influenza virus A/WSN/33 in the
      mouse olfactory system.
AB  - Invasion and persistence of the neuroadapted influenza virus A/WSN/33 in the
      mouse olfactory system was studied. WSN/33 instilled intranasally infected
      neurons in the olfactory epithelium and was transported in axons to the olfactory
      bulbs in wild type mice that survived the infection. In adult mice lacking the
      recombination activating gene 1 (RAG-1-/-), infected neurons occurred in the
      olfactory bulbs for 22-65 days after which the mice developed a rapidly
      progressive lethal infection affecting neurons in olfactory projection pathways,
      i.e. primary olfactory cortex, raphe in upper brainstem and hypothalamus. Adult
      mice without genes for interferon (IFN)-alpha/beta receptor, IFN-gamma receptor,
      inducible nitric oxide synthase (iNOS), IgH, the transporter associated with
      antigen processing 1 (TAP1), and natural killer cell-depleted mice, all survived
      the infection. Viral RNA was found in the olfactory bulbs in more than 80 per
      cent of the surviving iNOS-/-, IFN-gamma receptor-/-, and TAP1-/- mice. Taken
      together, this study shows that influenza A virus can invade the brain through
      the olfactory pathways and that the cellular immune responses prevent
      establishment of persistent infections in the olfactory bulbs. Furthermore,
      innate responses in olfactory bulbs may for a period of time keep the infection
      under control.

PMID- 14583157
TI  - Missed lower extremity and spine fractures in athletes.
AB  - The majority of missed fractures in athletes are not overlooked because of
      difficulties recognizing them on radiographs; rather, these fractures occur less
      commonly and often exist without accompanying disabilities, which makes their
      diagnosis more of a challenge. To complicate matters, evaluation of an injured
      athlete is often completed in the setting of the playing field, where
      distractions can be abundant. The physician treating sports-related injuries must
      not only follow the general principles of fracture evaluation and management, but
      must also be aware of the commonly understated fractures associated with the
      athlete's lower extremities and spine.

PMID- 14583158
TI  - Transdermal approaches to pain in sports injury management.
AB  - There is much lore about training room treatments for common overuse and
      traumatic musculoskeletal injuries. This review looks at the evidence behind many
      of the common transdermal treatments that are purported to reduce pain and
      inflammation and improve function. These include cryotherapy, laser treatments,
      electrical stimulation, ultrasound and phonophoresis, extracorporeal shock wave
      therapy, and iontophoresis. In addition, there are numerous over the counter
      sports creams and prescribed topical treatments that are routinely used. With the
      pressure to treat athletes safely and efficiently, sports practitioners must rely
      on well-proven evidence to build the most effective treatment plans.

PMID- 14583159
TI  - Pathophysiology of pain in sports.
AB  - The art and science of the management of musculoskeletal pain has advanced
      significantly over the past several years. With greater understanding of the
      nervous system's response to pain, and the biochemistry of this response,
      practitioners have a wider range of treatment options than ever before. The
      recognition of the importance of pain control in the recovery from
      musculoskeletal injury has resulted in the development of newer and more
      aggressive pain management strategies employing a variety of clinical techniques.
      Central to the appropriate use of these techniques is an understanding of
      physiology, psychology, and biochemistry of the pain response.

PMID- 14583160
TI  - Case report. Anorexia nervosa and psychosis in a male triathlete.

PMID- 14583161
TI  - Heat illness in children.
AB  - With an increasing number of children and adolescents involved in competitive
      athletics throughout the calendar year, the sports medicine team must be familiar
      with preventing and treating heat-related illness. Heat illness is a spectrum of
      illnesses from heat cramps to heat stroke. Mortality for heat stroke ranges from
      17% to 70%, depending on severity and age of the patient. Children are more
      susceptible to heat illness than adults for many reasons, including a greater
      surface area to body mass ratio, lower rate of sweating, and slower rate of
      acclimatization. The prevention of heat illness is based on recognizing and
      modifying risk factors, which include environmental conditions, clothing,
      hydration, and acclimatization. Once heat illness is suspected, treatment should
      begin immediately with rapid cooling procedures started on the field.

PMID- 14583162
TI  - Exercise during pregnancy: a practical approach.
AB  - Attitudes toward exercise during pregnancy have changed dramatically over the
      past 20 years. Recent studies show that, in most cases, exercise is safe for both
      the mother and fetus during pregnancy, and support the recommendation to initiate
      or continue exercise in most pregnancies. This report discusses the rationale
      behind the changes, and offers educational tools that may be employed to initiate
      behavioral change. We also propose exercise prescriptions for pregnant women who
      are sedentary, physically active, and competitive athletes. Armed with this
      information, the practitioner will be better equipped to counsel patients and
      incorporate a discussion on physical activity into prenatal visits.

PMID- 14583163
TI  - The multidisciplinary team approach to the outpatient treatment of disordered
      eating.
AB  - The multidisciplinary team approach to the patient with disordered eating is
      widely recognized as the best practice. Team members include a physician, a
      nutritionist, and a mental health professional. All should be experienced in the
      care of individuals with disordered eating. Each member of the treatment team has
      unique skills and responsibilities with respect to patient care. However, there
      is considerable overlap in what each member of the treatment team does to promote
      recovery from disordered eating. It is important to remember that eating problems
      exist on a spectrum from disordered eating behaviors that do not meet the
      Diagnostic and Statistical Manual of Mental Disorders criteria, to anorexia
      nervosa, and bulimia nervosa. Prognosis is directly related to duration of
      illness, so early intervention, even when symptoms may be minimal, is preferable.
      Despite multi- disciplinary treatment efforts, overall prognosis is poor, with
      only 40% to 50% of patients with anorexia nervosa and bulimia nervosa progressing
      to complete recovery. Continued efforts and early, comprehensive intervention
      must be undertaken by all practitioners.

PMID- 14583164
TI  - Prevention of pediatric sports injuries.
AB  - With over 30 million children participating in sports each year across the United
      States, a number of significant injuries are to be expected. Although mild
      injuries such as strains, sprains, and contusions predominate, catastrophic
      injuries do occur. Young athletes are at an increased risk for growth plate and
      apophyseal injuries, overuse injuries, and heat illness. Many of these sports
      injuries can be prevented. Prevention strategies include protective equipment,
      rule changes, preseason and season prevention interventions, safety measures,
      better coaching, education, and a societal awareness of injury and prevention.
      This article discusses current injury prevention for children participating in
      baseball, football, soccer, and ice hockey.

PMID- 14583165
TI  - Quality of care among disadvantaged women: adding income level to health
      datasets.

PMID- 14583166
TI  - Breast and cervical cancer screening for women between 50 and 69 years of age:
      what prompts women to screen?
AB  - The objective of this study was to examine mammography and cervical cancer
      screening rates among women aged 50 to 69 and to understand which prompts are
      effective for improving screening compliance. A self-administered survey was sent
      to 800 randomly selected participants in a health region in a relatively poor,
      rural province in Eastern Canada with a universal health care system. Since 1995,
      New Brunswick has instituted a biannual self-referral mammography screening
      program for women between 50 and 69 years of age. The response rate to the survey
      was 66%. Mammography screening compliance was 73% and was most significantly
      associated with annual clinical breast examinations, compliance with cervical
      cancer screening, and physician suggestion (p <.001). Cervical cancer screening
      compliance was 91% and was significantly associated with annual clinical breast
      examinations, compliance with mammography screening, and physician suggestion
      (p<.001). Contact with a physician is most effective for promoting screening
      compliance.

PMID- 14583167
TI  - Who continues using the diaphragm and who doesn't: implications for the
      acceptability of female-controlled HIV prevention methods.
AB  - OBJECTIVES: This study examines the acceptability of the diaphragm with the aim
      of facilitating the development of female-controlled human immunodeficiency virus
      (HIV) prevention methods. More specifically, we assess associations between being
      a current (vs. former) diaphragm user and characteristics that are hypothesized
      to influence the acceptability of contraceptive methods; and explore reasons for
      discontinuing use of the diaphragm among former diaphragm users. DESIGN: The
      study involved a cross-sectional telephone survey with women who were members of
      a nonprofit health maintenance organization and who were either a current (n =
      215) or former (n = 172) diaphragm user. METHODS: Participants were interviewed
      about the importance of contraceptive attributes; perceptions for the diaphragm;
      diaphragm use self-efficacy; perceived risk of and motivation to avoid pregnancy,
      HIV, and other sexually transmitted infections; and demographic characteristics,
      sexual, and contraceptive behavior. RESULTS: The likelihood of being a current
      diaphragm user (vs. former) increased with age, greater confidence in being able
      to use the diaphragm, greater perceived risk of pregnancy and more positive
      perceptions of the diaphragm. Women who valued attributes of hormonal
      contraceptives were less likely to be current users. Former diaphragm users
      reported that the following reasons were moderately to extremely important in
      their decision to stop using the diaphragm: difficulty inserting or removing the
      diaphragm (50.8%), dislike of leaving the diaphragm inside the vagina (46.8%),
      and wanting a more effective method for preventing pregnancy (44.2%).
      CONCLUSIONS: The findings suggest that specific characteristics of a product
      influence continued use and have implications for improving the acceptability of
      existing and new female-controlled HIV prevention methods.

PMID- 14583169
TI  - Phylogenetic invariants for the general Markov model of sequence mutation.
AB  - A phylogenetic invariant for a model of biological sequence evolution along a
      phylogenetic tree is a polynomial that vanishes on the expected frequencies of
      base patterns at the terminal taxa. While the use of these invariants for
      phylogenetic inference has long been of interest, explicitly constructing such
      invariants has been problematic. We construct invariants for the general Markov
      model of kappa-base sequence evolution on an n-taxon tree, for any kappa and n.
      The method depends primarily on the observation that certain matrices defined in
      terms of expected pattern frequencies must commute, and yields many invariants of
      degree kappa+1, regardless of the value of n. We define strong and parameter
      strong sets of invariants, and prove several theorems indicating that the set of
      invariants produced here has these properties on certain sets of possible pattern
      frequencies. Thus our invariants may be sufficient for phylogenetic applications.

PMID- 14583168
TI  - In their own voices: definitions and interpretations of physical activity.
AB  - Terms such as physical activity, exercise, and leisure are perceived and
      interpreted differently by people differing in gender, class, and sociocultural
      factors. We accessed multiple diverse data sources (including qualitative data
      recently collected in research and evaluation studies) to explore African
      American and American Indian women's (age 40+) definitions, meanings, and
      interpretations of "physical activity". These women reported that physical
      activity is typically considered to be structured "exercise" and not incidental
      activities of daily life. The term "leisure" was interpreted from a cultural
      perspective as being lazy. These women also had difficulty understanding the
      meaning of "intensity" (e.g., "moderate", "vigorous"). Researchers must
      acknowledge and understand inconsistencies that arise and how these might
      influence design of, and responses to, self-report assessment of physical
      activity.

PMID- 14583171
TI  - Effect of channel geometry on the electrostatic potential in acetylcholine
      channels.
AB  - We study the effect of channel geometry on the potential barrier encountered by
      ions as they permeate the acetylcholine receptor channel. Among the various
      channel geometries which have been used to represent the acetylcholine receptor
      channel include the cylinder and the toroidal catenary. The main reasons for
      those choices appear to be the facilitation of separation of the Poisson
      equation, rather than biological considerations. We consider a novel and
      realistic acetylcholine channel geometry, and calculate the electrostatic
      potential profiles within it, and compare our results with results from other
      channel geometries.

PMID- 14583170
TI  - Quantification of the effect of control strategies on classical swine fever
      epidemics.
AB  - Emergency vaccination during an epidemic of classical swine fever virus (CSFV)
      has become a serious option because of the ethical problems of strategies with
      massive culling and the availability of a marker vaccine that reduces virus
      transmission. Here we present a model of between-herd CSFV transmission, which
      quantifies the effect of control strategies with and without vaccination. We
      estimate the model parameters from data of the Dutch CSFV epidemic of 1997/1998.
      With the model, a set of control strategies is compared, consisting of five
      control measures in several combinations. Consequently, the following general
      requirements of successful strategies can be formulated. First, to achieve
      extinction of a CSFV epidemic, transmission through transport should be prevented
      and the indirect virus transmission, i.e. all transmission not through animal
      contacts, should at least be halved, either by vaccination or by culling of the
      susceptible pig population. Second, to minimize the size and duration of an
      epidemic, the extinction requirements should be met quickly and indirect virus
      transmission should be reduced by far more than a half. Although the origin of
      the model parameters let the requirements in fact be only applicable for the
      south-eastern part of the Netherlands, it is argued that epidemics in other areas
      will not need stricter control strategies.

PMID- 14583172
TI  - The dynamics of two viral infections in a single host population with
      applications to hantavirus.
AB  - An SI epidemic model for a host with two viral infections circulating within the
      population is developed, analyzed, and numerically simulated. The model is a
      system of four differential equations which includes a state for susceptible
      individuals, two states for individuals infected with a single virus, one which
      is vertically transmitted and the other which is horizontally transmitted, and a
      fourth state for individuals infected with both viruses. A general growth
      function with density-dependent mortality is assumed. A special case of this
      model, where there is no coinfection and total cross immunity, is thoroughly
      analyzed. Several threshold values are defined which determine establishment of
      the disease and persistence at equilibrium for one or both of the infections
      within the host population. The model has applications to a hantavirus and an
      arenavirus that infect cotton rats. The hantavirus is transmitted horizontally
      whereas the arenavirus is transmitted vertically. It is shown through analysis
      and numerical simulations that both diseases can be maintained within a single
      host population, where individuals can be either infected with both viruses or
      with a single virus.

PMID- 14583173
TI  - Leptin responses to antecedent exercise and hypoglycemia in healthy and type 1
      diabetes mellitus men and women.
AB  - These studies examined the effects of hypoglycemia or exercise on leptin levels
      in 47 (23 women, 24 men) healthy (age 26+/-2 years, body mass index 23+/-0.5
      kg.m(-2)) and type 1 diabetes mellitus (T1DM) subjects (age 29+/-2 years, body
      mass index 27+/-2 kg.m(-2)). In Study 1, healthy and T1DM subjects were exposed
      to morning and afternoon 120-min hyperinsulinemic hypoglycemic ( approximately 50
      mg/dl) or euglycemic ( approximately 90 mg/dl) clamps. In Study 2, healthy
      subjects were studied during morning and afternoon 90-min exercise bouts at 50%
      VO(2max). In Study 1, basal levels of leptin were significantly greater in T1DM
      vs. the healthy subjects (13.8+/-3 vs. 5.4+/-1 ng/dl; P<.05). However, during the
      last 30 min of morning hypoglycemia, plasma leptin levels significantly decreased
      from 5.4+/-1 to 4.0+/-1 ng/dl (P<.05) and remained low during afternoon
      hypoglycemia (4.3+/-1 ng/dl) in healthy but not T1DM subjects. In Study 2, plasma
      leptin levels did not significantly change during exercise the bout in healthy
      men, but significantly decreased 3 h after morning exercise, and continued to
      decrease during afternoon exercise in healthy women (P<.0001). Thus, plasma
      leptin levels decrease in response to hypoglycemia in healthy but not T1DM
      subjects. However, T1DM patients do have increased basal leptin levels compared
      to healthy man. Lastly, there is a marked sexual dimorphism in plasma leptin
      responses to repeated episodes of exercise.

PMID- 14583174
TI  - Starting patients with type 2 diabetes on insulin therapy using once-daily
      injections of biphasic insulin aspart 70/30, biphasic human insulin 70/30, or NPH
      insulin in combination with metformin.
AB  - Transitioning safely to insulin therapy when oral antidiabetic agents fail to
      provide adequate glycemic control is a critical aspect of care for the patient
      with type 2 diabetes mellitus (T2DM). We evaluated the clinical effectiveness of
      starting patients on a relatively simple regimen of once-daily injections of
      either biphasic insulin aspart 70/30 (10 min before dinner), NPH insulin (at 10
      p.m.), or biphasic human insulin 70/30 (30 min before dinner) in combination with
      metformin. Enrolled patients had T2DM and inadequate glycemic control
      (AlC>/=7.5%) on a previous regimen of metformin as monotherapy or in combination
      with a sulphonylurea. One hundred and forty (140) patients received metformin
      monotherapy for 4 weeks followed by 12 weeks of combination treatment with
      metformin and once-daily insulin injections. AlC levels decreased from baseline
      by 1.1-1.3% for patients in each of the three treatment groups. Overall, FPG
      values decreased from baseline by 31% (biphasic insulin aspart), 37% (NPH
      insulin), and 28% (biphasic human insulin). Subjects whose final FPG level was
      <126 mg/dl experienced the largest decreases in AlC values (-2.3%, -1.9%, -1.8%,
      respectively). All three treatment regimens were well tolerated. The results
      indicate that patients with T2DM can safely and effectively begin insulin therapy
      using once-daily injections of biphasic insulin aspart 70/30, biphasic human
      insulin 70/30, or NPH insulin in combination with metformin.

PMID- 14583176
TI  - Diabetes mellitus and comorbidity. Change between 1984-1986 and 1995-1997:
      results of the Nord-Trondelag Health Study.
AB  - The prevention of diabetic complications is a challenge to the health services. A
      health survey was carried out in the Nord-Trondelag county of Norway during the
      period 1984-1986 (77,224 respondents) and repeated in 1995-1997 (65,599
      respondents). In this study, self-reports of diabetes and other diseases and
      impairments in the two screenings are compared. Did respondents report more or
      less morbidity in 1995-1997 than in 1984-1986? Comparisons between self-reports
      in the two surveys show higher morbidity among young people (below 40 years of
      age) in 1995-1997 than in 1984-1986, both among people with and without diabetes,
      but the change was not statistically significant. For the middle-aged (40-59
      years of age), there were smaller changes. For older people (above 60 years of
      age) with diabetes, there was a decrease in some of the reported morbidity,
      namely for cerebral stroke, mobility impairment, and impairment due to other
      physical diseases, compared to older people without diabetes. There was a slight
      increase in reported vision impairment, but smaller than for people without
      diabetes. The changes in relative risk for people with stroke, mobility and
      vision impairment, and other physical disease are statistically significant.
      Splitting the sample according to gender, this trend was only significant among
      women.

PMID- 14583175
TI  - Design of the cooperative study on glycemic control and complications in diabetes
      mellitus type 2: Veterans Affairs Diabetes Trial.
AB  - INTRODUCTION: Long-term glycemic control trials in type 2 diabetes show as the
      main clinical benefit a difference in retinal photocoagulation (3/1000 in the UK
      Prospective Diabetes Study [UKPDS]), but no effect on visual acuity or renal
      failure. No intensive glycemic control trial has yet affected cardiovascular (CV)
      events, the main cause of morbidity and mortality. By contrast, modest blood
      pressure reduction has protective effects on visual acuity, renal function, CV
      events, and mortality. Optimal glycemic control goals are not established in
      elderly, obese persons with advanced complications, the most common patients in
      the Veterans Affairs (VA) system. The earlier feasibility trial in such patients
      (VA-CSDM) suggested potentially worse CV outcomes with lower attained hemoglobin
      A1c (HbA1c) levels. OBJECTIVES: The primary objective of the Veterans Affairs
      Diabetes Trial (VADT) is the assessment of the effect of intensive glycemic
      treatment on CV events. Other objectives are effects on microangiopathy, quality
      of life, and cost effectiveness. RESEARCH DESIGN AND METHODS: The VADT, started
      in December 2000, is enrolling 1700 men and women previously uncontrolled on
      insulin or maximum doses of oral agents at 20 VA medical centers. Accrual is 2
      years and follow-up is 5-7 years, with visits every 1.5 months. The study has a
      power of 86% to detect a 21% relative reduction in major CV events (CV death,
      myocardial infarction [MI], cerebrovascular accident [CVA], congestive heart
      failure [CHF], revascularization and amputation for ischemia). Subjects are
      randomized to an intensive arm aiming at normal HbA1c levels or to a standard arm
      with usual, improved glycemic control. An HbA1c separation of >1.5% is to be
      maintained (expected 2%). Both arms receive step therapy: glimepiride or
      metformin plus rosiglitazone and addition of insulin or other oral agents to
      achieve goals. Strict control of blood pressure and dyslipidemia, daily aspirin,
      diet, and education are identical in both arms. Plasma fibrinogen, plasminogen
      activating inhibitor I (PAI-I), lipids, renal function parameters, and ECG are
      measured throughout. Stereo retinal photographs are obtained at entry and 5
      years, eye examinations yearly, and intervention as needed to prevent visual
      deterioration. Recruitment is proceeding on schedule: the current mean HbA1c at
      entry is 9.4+/-1.6% and mean duration of diagnosed diabetes 11+/-8 years.

PMID- 14583177
TI  - Increased hospital expenditures in diabetic patients hospitalized for
      cardiovascular diseases.
AB  - OBJECTIVES: To measure the impact of diabetes on hospital resource use and
      expenditures in patients hospitalized for cardiovascular diseases (CVD). RESEARCH
      DESIGN AND METHODS: We conducted an observational study of 4865 hospitalizations
      for CVD over 2 years (January 1998 to December 1999). Information with respect of
      the presence of diabetes mellitus, length of stay, readmissions, mortality, and
      costs were obtained through retrospective chart review. RESULTS: Diabetic
      patients accounted for 35.1% of hospital admissions (1706 admissions), 40.8% of
      hospital stays (23,309 days), and 39% of direct medical cost (5,735,884 euros).
      On average, diabetic patients had longer hospital stay (13.6+/-13.2 vs. 10.7+/
      11.2 days; P<.001) and direct in-patient cost (3438+/-4308 vs. 2513+/-3384 euros;
      P<.001) and experienced more readmissions (relative risk: 1.67; 95% CI: 1.45
      1.91) compared with nondiabetic patients. However, despite the hospital mortality
      rate being higher in nondiabetic patients (6.3% vs. 5.8%), these results were not
      statistically significant (relative risk: 1.09; 95% CI: 0.86-1.40). CONCLUSIONS:
      Diabetic patients hospitalized for CVD have longer hospital stay, greater risk of
      short-term readmission, and are more costly than nondiabetic patients. However,
      in-hospital mortality risk in patients hospitalized by CVD is no greater in
      diabetic than in nondiabetics.

PMID- 14583178
TI  - Urinary sorbitol measurement and the effect of an aldose reductase inhibitor on
      its concentration in the diabetic state.
AB  - The amounts of sorbitol (SOR) excreted in 24-h urine were determined on two
      groups, i.e., diabetic and nondiabetic patients, using an improved method in
      which ion exchange resin column processing was applied, and these levels were
      compared with SOR levels in whole blood. Urinary SOR concentration was also
      determined in diabetic and normal rats in the same manner and its relationship to
      aldose reductase (AR) activity in whole blood was investigated. Changes in SOR
      levels in urine and whole blood were compared in diabetic rats after
      administration of an AR inhibitor (ARI). Whole blood SOR levels and urinary SOR
      excretion were significantly higher in diabetic patients than in nondiabetic
      patients. The same results were obtained in the animal models. In diabetic rats,
      the urinary SOR excretion was about five times higher than that in control rats,
      and the AR activity in whole blood was also significantly higher. The increase in
      urinary SOR excretion and whole blood SOR levels, as well as AR activity, in
      blood in the diabetic state was inhibited by ARI administration. The influence of
      the diabetic state and the efficacy of the ARI were more marked in urinary SOR
      excretion than in whole blood SOR levels. These data indicate that determinations
      of urinary SOR excretion and AR activity are easily measurable and of benefit to
      assessing the diabetic condition.

PMID- 14583180
TI  - Effect of low-density lipoprotein apheresis on plasma endothelin-1 levels in
      diabetic hemodialysis patients with arteriosclerosis obliterans.
AB  - Endothelin (ET)-1 has been implicated in the pathogenesis of diabetes,
      arteriosclerosis, and chronic renal failure. We studied whether low-density
      lipoprotein (LDL) apheresis alters plasma ET-1 levels in diabetic hemodialysis
      patients with arteriosclerosis obliterans (ASO). Plasma ET-1 levels were measured
      in 30 healthy control subjects (Group A), 30 diabetes patients without ASO (Group
      B), 20 diabetes patients with ASO (Group C), 20 diabetes patients without ASO who
      were undergoing hemodialysis (Group D), and 6 diabetes patients with ASO who were
      undergoing hemodialysis (Group E). Hemodialysis patients were dialyzed three
      times weekly with a bicarbonate dialysate. Six diabetic hemodialysis patients
      with ASO underwent LDL apheresis once weekly for 10 weeks, and the change in
      plasma ET-1 levels due to LDL apheresis was measured. LDL apheresis resulted in a
      statistically significant decrease in levels of total cholesterol and LDL
      cholesterol. In addition, LDL apheresis improved clinical symptoms in all
      patients. Plasma ET-1 levels in Group E (15.0+/-1.9 pg/ml) were significantly
      higher than those in Groups A (1.0+/-0.6 pg/ml, P<.001), B (1.3+/-0.5 pg/ml,
      P<.001), C (5.6+/-1.0 pg/ml, P<.001), and D (10.4+/-1.6 pg/ml, P<.01). Plasma ET
      1 levels decreased progressively and significantly after a single LDL apheresis
      began (9.4+/-1.0 pg/ml after 60 min, P<.001, and 6.0+/-1.0 pg/ml after 120 min,
      P<.001). These data suggest that ET-1 may be associated with arteriosclerosis and
      that LDL apheresis enhances peripheral microcirculation in part by reducing the
      production of ET-1 in diabetic hemodialysis patients with ASO.

PMID- 14583179
TI  - Serum and urinary nitric oxide in Type 2 diabetes with or without
      microalbuminuria: relation to glomerular hyperfiltration.
AB  - BACKGROUND: Glomerular hyperfiltration is considered as one of the
      pathophysiological mechanisms for the development of diabetic nephropathy.
      Oxidative stress is enhanced in patients with diabetes mellitus. Reportedly,
      nitric oxide (NO) might be involved in the pathogenesis of hyperfiltration. We
      investigated the relationship between hyperfiltration and NO system, and
      malondialdehyde (MDA) levels in Type 2 diabetics with/without microalbuminuria.
      METHODS: In 39 microalbuminuric, 29 normoalbuminuric Type 2 diabetic patients and
      32 healthy controls, serum creatinine, nitrite, nitrate, urinary microalbumin,
      nitrite, nitrate, plasma MDA and estimated glomerular filtration rate (EGFR)
      values, calculated according to the Cockcroft and Gault formula, were recorded.
      RESULTS: Serum and urine NO levels were higher in both microalbuminurics and
      normoalbuminurics than controls. There were no significant differences in EGFR
      between groups. However, hyperfiltration was determined in 31% of
      normoalbuminurics and 20% of microalbuminurics. Serum and urine NO levels were
      higher in patients with hyperfiltration. Plasma MDA levels were significantly
      elevated in both microalbuminurics and normoalbuminurics when compared with
      controls. Serum glucose and microalbuminuria were positively correlated in
      microalbuminuric diabetics. Serum NO levels were also positively correlated with
      EGFR in both normoalbuminurics and microalbuminurics. HbA1c levels were
      positively correlated with both urinary albumin excretion and plasma MDA levels
      in normoalbuminuric diabetics. CONCLUSIONS: Hyperglycemia is associated with an
      increased NO biosynthesis and lipid peroxidation. Increased oxidative stress may
      contribute to the high NO levels in Type 2 diabetes. Furthermore, the high NO
      levels may lead to hyperfiltration and hyperperfusion, which in turn leads to an
      increase in urinary albumin excretion and thus causes progression of nephropathy
      in early Type 2 diabetes.

PMID- 14583181
TI  - High glucose-induced alterations of extracellular matrix of human skin
      fibroblasts are not dependent on TSP-1-TGFbeta1 pathway.
AB  - Elevated glucose level is the main cause of extracellular matrix (ECM)
      derangement in various tissues in diabetes mellitus. The development of diabetic
      nephropathy is considered to be dependent on profibrotic cytokine, transforming
      growth factor-beta1 (TGFbeta1). Its excessive activation due to the up-regulation
      of thrombospondin-1 (TSP-1) in mesangial cells exposed to high glucose
      contributes to ECM accumulation. However, the role of TSP-1-TGFbeta1 pathway in
      the development of glucose-induced imbalance of ECM homeostasis in skin
      connective tissue is not studied. We investigated the response of human skin
      fibroblasts to elevated glucose level (11.0 and 30.0 mM) in terms of: (1) the
      expression and secretion of fibronectin (FN) and plasminogen activator inhibitor
      1 (PAI-1); (2) the accumulation of hyaluronic acid (HA) in pericellular matrix
      and in the conditioned medium; (3) TGFbeta1 expression, secretion and activation;
      (4) TSP-1 expression and secretion. We demonstrated the up-regulation of FN and
      PAI-1 by elevated glucose and the stimulation of HA accumulation in both cellular
      compartments. However, we failed to demonstrate the increase of expression,
      secretion and activation of TGFbeta1, and the increase of TSP-1 expression and
      secretion in fibroblasts exposed to high glucose. These results show that ECM
      derangement in skin fibroblasts due to high glucose is not determined by TGFbeta1
      and its activation by TSP-1.

PMID- 14583182
TI  - High prevalence of asymptomatically poor muscle perfusion of lower extremities
      measured in type II diabetes patients with abnormal myocardial perfusion.
AB  - Foot problems are the most common cause of hospital admission in patients with
      type II diabetes mellitus (DM). Poor muscle perfusion of lower extremities is
      thought to be the major component in the pathogenesis of foot problems.
      Therefore, it is important and interesting to investigate if high prevalence of
      poor muscle perfusion of lower extremities in type II DM patients with abnormal
      myocardial perfusion and more cardiovascular risk factors. We used a well
      established and noninvasive radionuclide method (Xe-133 muscle washout) to
      objectively evaluate the anterior tibial muscle perfusion of 60 type II DM male
      patients without symptoms/signs of peripheral vascular disease (PVD) in the lower
      extremities. The patients were separated into groups according to the myocardial
      perfusion imaging results and cardiovascular risk factor survey. Meanwhile, 30
      normal male controls with a matched age distribution were also included for
      comparison. The muscle perfusions were of significant difference (P-values <.05)
      between (1) 60 type II DM patients (1.84+/-0.43 ml/100 g/min) and 30 normal
      controls (2.95+/-0.52 ml/100 g/min), (2) 24 patients with abnormal myocardial
      perfusion (1.31+/-0.45 ml/100 g/min) and 36 patients with normal myocardial
      perfusion (2.24+/-0.48 ml/100 g/min), as well as (3) 28 patients with more
      cardiovascular risk factors (1.33+/-0.46 ml/100 g/min) and 22 patient with less
      cardiovascular risk factors (2.22+/-0.49 ml/100 g/min). Based on Xe-133 muscle
      washout method, we concluded that the muscle perfusion in the lower extremities
      of type II DM patients without symptoms/signs of PVD is significantly decreased
      and related to abnormal myocardial perfusion and more cardiovascular risk
      factors.

PMID- 14583183
TI  - Genetic variants of hepatocyte nuclear factor-1beta in Chinese young-onset
      diabetic patients with nephropathy.
AB  - In Hong Kong, the prevalence of diabetes is estimated to be 2% in the young
      population. In the diabetic population, 30% of patients have diagnosis before the
      age of 40 years. Besides, 30% of young diabetic patients have varying degrees of
      albuminuria. Mutations in the gene encoding the hepatocyte nuclear factor (HNF)
      1beta are associated with a subtype of maturity-onset diabetes of the young (MODY
      5) characterized by urogenital abnormalities. We examined 74 unrelated Chinese
      subjects with young-onset diabetes complicated by nephropathy for variants in
      this gene. The HNF-1beta gene was screened by direct sequencing and the
      functional properties of wild-type and mutant proteins were analyzed by
      transactivation analysis.A novel variant in exon 3 (E260D) was found in one
      patient. Extended family analysis revealed four other siblings carrying this
      variant. One subject had diabetes and another had impaired glucose tolerance.
      Another sibling had microalbuminuria but normal glucose tolerance. Transfection
      studies showed insignificant differences in transactivation ability between wild
      type and mutated HNF-1beta. A silent polymorphism Q378Q was identified in another
      unrelated subject. These results suggest genetic variants in HNF-1beta are not a
      common cause of young-onset diabetes or diabetic nephropathy in Chinese, but may
      modify disease manifestation and progression. Other potential candidate genes
      should be looked for to account for the high prevalence of young-onset diabetes
      and nephropathy in this population.

PMID- 14583184
TI  - Long-term treatment with fidarestat suppresses the development of diabetic
      retinopathy in STZ-induced diabetic rats.
AB  - It is important to suppress retinal vascular changes for prevention of the onset
      and progression of diabetic retinopathy. In the present study, we investigated
      the dose-response effect of an aldose reductase (AR) inhibitor, fidarestat, on
      retinal vascular changes in the retinas of streptozotocin (STZ)-induced diabetic
      rats. Fidarestat (0.5, 1, and 2 mg/kg) was administered once a day, from 4 days
      after STZ injection, for 15 months. Microaneurysms and thickness of the basement
      membrane were frequently observed in the untreated diabetic group as compared to
      the nondiabetic control group. In addition, the number of pericytes decreased in
      the untreated diabetic group. Fidarestat diminished the prevalence rate of
      microaneurysms, basement membrane thickness and decrease in the number of
      pericytes, and complete suppression was observed at a dose of 2 mg/kg. Fidarestat
      also dose-dependently inhibited sorbitol accumulation in the retina. Furthermore,
      a close correlation was observed between the prevalence rate of microaneurysms
      and the decrease in the number of pericytes, which indicated that damage to
      pericytes triggers retinal vascular changes. These results suggest that
      fidarestat, by virtue of its long-term correction of the accelerated polyol
      pathway, has a potential role in preventing the progression of diabetic
      retinopathy.

PMID- 14583185
TI  - Cerivastatin ameliorates high insulin-enhanced neutrophil-endothelial cell
      adhesion and endothelial intercellular adhesion molecule-1 expression by
      inhibiting mitogen-activated protein kinase activation.
AB  - BACKGROUND AND AIMS: There is growing evidence that hyperinsulinemia is linked to
      the development of atherosclerosis in patients with diabetes. We demonstrated
      previously that high insulin exacerbates neutrophil-endothelial cell adhesion and
      endothelial intercellular adhesion molecule (ICAM)-1 expression through
      activation of protein kinase C (PKC) and mitogen-activated protein (MAP) kinase.
      Though 3-hydroxymethyl-3-glutaryl coenzyme A (HMG-CoA) reductase inhibitors
      (statins) have been employed as therapeutic agents in the treatment of
      dyslipidemia, which is frequently accompanied by diabetes mellitus; it is not
      known whether statins protect against leukocyte-endothelial interactions,
      especially in hyperinsulinemia. In this study, we determined which statin(s)
      could protect against endothelial reactions to high insulin. METHODS: Studies of
      adhesion between neutrophils from healthy volunteers and human umbilical vein
      endothelial cells incubated in regular insulin-rich medium with or without
      statins were performed. Adhered neutrophils were quantified by measuring their
      myeloperoxidase (MPO) activities, and endothelial expression of ICAM-1 was
      examined using an enzyme immunoassay. RESULTS: Both the increased neutrophil
      endothelial cell adhesion and ICAM-1 expression caused by high insulin (100
      microU/ml) for 48 h were significantly attenuated by pretreatment with
      cerivastatin (0.01 microM), but not by fluvastatin (0.5 microM) or pravastatin
      (0.05 microM). These protective actions of cerivastatin were attenuated by a key
      intermediate in the cholesterol biosynthesis pathway, mevalonate (400 microM). In
      addition, cerivastatin attenuated both neutrophil-endothelial cell adhesion and
      endothelial ICAM-1 expression enhanced by a MAP kinase activator, anisomycin (1
      microM) but not by a PKC activator, PMA (10 nM). CONCLUSIONS: These results
      suggest that through inhibiting MAP kinase but not PKC activation therapy with
      cerivastatin would be promising strategy for inhibiting neutrophil-endothelial
      cell adhesion and endothelial ICAM-1 expression enhanced by high insulin, which
      is closely correlated with atherosclerosis.

PMID- 14583187
TI  - A "polyORFomic" analysis of prokaryote genomes using disabled-homology filtering
      reveals conserved but undiscovered short ORFs.
AB  - Prokaryote gene annotation is complicated by large numbers of short open reading
      frames (ORFs) that arise naturally from genetic code design. Historically, many
      hypothetical ORFs have been annotated as genes in microbes, usually with an
      arbitrary length threshold (e.g. greater than 100 codons). Given the use of such
      thresholds, what is the extent of genuine undiscovered short genes in the current
      sampling of prokaryote genomes? To assess rigorously the potential under
      annotation of short ORFs with homology, we exhaustively compared the polyORFome-
      all possible ORFs in 64 prokaryotes (53 bacteria and 11 archaea) plus budding
      yeast--to itself and to all known proteins. The novelty of our analysis is that,
      firstly, sequence comparisons to/between both annotated and un-annotated ORFs are
      considered, and secondly a two-step disabled-homology filter is applied to set
      aside putative pseudogenes and spurious ORFs. We find that un-annotated
      homologous short ORFs (uhORFs) correspond to a small but non-negligible fraction
      of the annotated prokaryote proteomes (0.5-3.8%, depending on selection
      criteria). Moreover, the disabled-homology filter indicates that about a third of
      uhORFs correspond to putative pseudogenes or spurious ORFs. Our analysis shows
      that the use of annotation length thresholds is unnecessary, as there are
      manageable numbers of short ORF homologies conserved (without disablements)
      across microbial genomes. Data on uhORFs are available from
      http://pseudogene.org/polyo

PMID- 14583186
TI  - CC-chemokine receptor CCR5-del32 mutation as a modifying pathogenetic factor in
      type I diabetes.
AB  - The purpose of this study was to determine the CCR5-del32 allele frequency in
      type I (insulin-dependent) and type II (noninsulin-dependent) diabetes patients,
      and to test whether and how this mutation is associated with both types of
      diabetes. Thirty-eight type I diabetes and 111 type II diabetes patients'
      genotyping was performed by polymerase chain reaction assaying, and amplified
      products were digested with restriction enzyme EcoRI. The results were analyzed
      using statistical methods. No statistical differences were found in CCR5-del32
      allele frequencies in types I and II diabetes patients compared with the control
      group of native Estonians. However, an association exists between CCR5 gene
      polymorphism and the clinical course of type I diabetes. In the case of wild-type
      CCR5, the disease starts at an earlier age. In type II diabetes, there was a
      difference between genotypes in morbidity to concomitant diseases, being higher
      in the CCR5 wild-type genotype.

PMID- 14583188
TI  - Identification of the antigenic epitopes in staphylococcal enterotoxins A and E
      and design of a superantigen for human cancer therapy.
AB  - Monoclonal antibodies have a potential for cancer therapy that may be further
      improved by linking them to effector molecules such as superantigens. Tumor
      targeting of a superantigen leads to a powerful T cell attack against the tumour
      tissue. Encouraging results have been observed preclinically and in patients
      using the superantigen staphylococcal enterotoxin A, SEA. To further improve the
      concept, we have reduced the reactivity to antibodies against superantigens,
      which is found in all individuals. Using epitope mapping, antibody binding sites
      in SEA and SEE were found around their MHC class II binding sites. These epitopes
      were removed genetically and a large number of synthetic superantigens were
      produced in an iterative engineering procedure. Properties such as decreased
      binding to anti-SEA as well as higher selectivity to induce killing of tumour
      cells compared to MHC class II expressing cells, were sequentially improved. The
      lysine residues 79, 81, 83 and 84 are all part of major antigenic epitopes,
      Gln204, Lys74, Asp75 and Asn78 are important for optimal killing of tumour cells
      while Asp45 affects binding to MHC class II. The production properties were
      optimised by further engineering and a novel synthetic superantigen, SEA/E-120,
      was designed. It is recognised by approximately 15% of human anti-SEA antibodies
      and have more potent tumour cell killing properties than SEA. SEA/E-120 is likely
      to have a low toxicity due to its reduced capacity to mediate killing of MHC
      class II expressing cells. It is produced as a Fab fusion protein at
      approximately 35 mg/l in Escherichia coli.

PMID- 14583189
TI  - Phase diagram of nucleosome core particles.
AB  - We present a phase diagram of the nucleosome core particle (NCP) as a function of
      the monovalent salt concentration and applied osmotic pressure. Above a critical
      pressure, NCPs stack on top of each other to form columns that further organize
      into multiple columnar phases. An isotropic (and in some cases a nematic) phase
      of columns is observed in the moderate pressure range. Under higher pressure
      conditions, a lamello-columnar phase and an inverse hexagonal phase form under
      low salt conditions, whereas a 2D hexagonal phase or a 3D orthorhombic phase is
      found at higher salt concentration. For intermediate salt concentrations,
      microphase separation occurs. The richness of the phase diagram originates from
      the heterogeneous distribution of charges at the surface of the NCP, which makes
      the particles extremely sensitive to small ionic variations of their environment,
      with consequences on their interactions and supramolecular organization. We
      discuss how the polymorphism of NCP supramolecular organization may be involved
      in chromatin changes in the cellular context.

PMID- 14583190
TI  - Antisense-RNA mediated transcriptional attenuation: importance of a U-turn loop
      structure in the target RNA of plasmid pIP501 for efficient inhibition by the
      antisense RNA.
AB  - Antisense-RNA mediated gene regulation has been found and studied in detail
      mainly in prokaryotic accessory DNA elements. In spite of different regulatory
      mechanisms, in all cases a rapid interaction between antisense and target RNA has
      been shown to be crucial for efficient regulation. Recently, a sequence
      comparison revealed in 45 antisense RNA control systems a 5' YUNR motif
      indicative for the formation of a U-turn structure in either an antisense or a
      target RNA loop and confirmed in the case of the hok/sok system of plasmid R1 its
      importance for regulation.Here, we demonstrate the importance of the 5' YUNR
      motif in the target RNA (RNAII) loop L1 of the replication control system of
      plasmid pIP501. The effect of four individual mutations in L1 was studied in vivo
      and in vitro. Mutations that maintained the putative U-turn or swapped it from
      sense to antisense RNA were silent, whereas mutations that eliminated the 5'-YUNR
      motif showed two- to threefold elevated copy numbers in vivo in correlation with
      three- to fourfold reduced inhibition rate constants of the complementary RNAIII
      species in vitro, whereas the half-lives of all RNAIII species were not affected.
      ENU probing experiments confirmed the U-turn structure for the silent mutation (N
      C) and disruption of this structure upon alteration of the invariant U or
      inversion of the YUNR motif-containing loop. RNA secondary structure probing
      excluded loop size alterations as a reason for altered inhibition rates.
      Implications for the pathway and efficiency of RNAII/RNAIII interaction, and
      hence, pIP501 copy-number control, are discussed.

PMID- 14583191
TI  - Insights into catalysis by a knotted TrmD tRNA methyltransferase.
AB  - The crystal structure of Escherichia coli tRNA (guanosine-1) methyltransferase
      (TrmD) complexed with S-adenosyl homocysteine (AdoHcy) has been determined at
      2.5A resolution. TrmD, which methylates G37 of tRNAs containing the sequence
      G36pG37, is a homo-dimer. Each monomer consists of a C-terminal domain connected
      by a flexible linker to an N-terminal AdoMet-binding domain. The two bound AdoHcy
      moieties are buried at the bottom of deep clefts. The dimer structure appears
      integral to the formation of the catalytic center of the enzyme and this
      arrangement strongly suggests that the anticodon loop of tRNA fits into one of
      these clefts for methyl transfer to occur. In addition, adjacent hydrophobic
      sites in the cleft delineate a defined pocket, which may accommodate the GpG
      sequence during catalysis. The dimer contains two deep trefoil peptide knots and
      a peptide loop extending from each knot embraces the AdoHcy adenine ring.
      Mutational analyses demonstrate that the knot is important for AdoMet binding and
      catalytic activity, and that the C-terminal domain is not only required for tRNA
      binding but plays a functional role in catalytic activity.

PMID- 14583192
TI  - The muscle ankyrin repeat proteins: CARP, ankrd2/Arpp and DARP as a family of
      titin filament-based stress response molecules.
AB  - CARP, ankrd-2/Arpp, and DARP, are three members of a conserved gene family,
      referred to here as MARPs (muscle ankyrin repeat proteins). The expression of
      MARPs is induced upon injury and hypertrophy (CARP), stretch or denervation
      (ankrd2/Arpp), and during recovery following starvation (DARP), suggesting that
      they are involved in muscle stress response pathways. Here, we show that MARP
      family members contain within their ankyrin repeat region a binding site for the
      myofibrillar elastic protein titin. Within the myofibril, MARPs, myopalladin, and
      the calpain protease p94 appear to be components of a titin N2A-based signaling
      complex. Ultrastructural studies demonstrated that all three endogenous MARP
      proteins co-localize with I-band titin N2A epitopes in adult heart muscle
      tissues. In cultured fetal rat cardiac myocytes, passive stretch induced
      differential distribution patterns of CARP and DARP: staining for both proteins
      was increased in the nucleus and at the I-band region of myofibrils, while DARP
      staining also increased at intercalated discs. We speculate that the myofibrillar
      MARPs are regulated by stretch, and that this links titin-N2A-based myofibrillar
      stress/strain signals to a MARP-based regulation of muscle gene expression.

PMID- 14583193
TI  - The occupancy of ions in the K+ selectivity filter: charge balance and coupling
      of ion binding to a protein conformational change underlie high conduction rates.
AB  - Potassium ions diffuse across the cell membrane in a single file through the
      narrow selectivity filter of potassium channels. The crystal structure of the
      KcsA K+ channel revealed the chemical structure of the selectivity filter, which
      contains four binding sites for K+. In this study, we used Tl+ in place of K+ to
      address the question of how many ions bind within the filter at a given time,
      i.e. what is the absolute ion occupancy? By refining the Tl+ structure against
      data to 1.9A resolution with an anomalous signal, we determined the absolute
      occupancy of Tl+. Then, by comparing the electron density of Tl+ with that of K+,
      Rb+ and Cs+, we estimated the absolute occupancy of these three ions. We further
      analyzed how the ion occupancy affects the conformation of the selectivity filter
      by analyzing the structure of KcsA at different concentrations of Tl+. Our
      results indicate that the average occupancy for each site in the selectivity
      filter is about 0.63 for Tl+ and 0.53 for K+. For K+, Rb+ and Cs+, the total
      number of ions contained within four sites in the selectivity filter is about
      two. At low concentrations of permeant ion, the number of ions drops to one in
      association with a conformational change in the selectivity filter. We conclude
      that electrostatic balance and coupling of ion binding to a protein
      conformational change underlie high conduction rates in the setting of high
      selectivity.

PMID- 14583194
TI  - The denatured state of Engrailed Homeodomain under denaturing and native
      conditions.
AB  - Protein folding starts from the elusive form of the denatured state that is
      present under conditions that favour the native state. We have studied the
      denatured state of Engrailed Homeodomain (En-HD) under mildly and strongly
      denaturing conditions at the level of individual residues by NMR and more
      globally by conventional spectroscopy and solution X-ray scattering. We have
      compared these states with a destabilized mutant, L16A, which is predominantly
      denatured under conditions where the wild-type is native. This engineered
      denatured state, which could be directly studied under native conditions, was in
      genuine equilibrium with the native state, which could be observably populated by
      changing the conditions or introducing a stabilizing mutation. The denatured
      state had extensive native secondary structure and was significantly compact and
      globular. But, the side-chains and backbone were highly mobile. Non-cooperative
      melting of the residual structure on the denatured state of En-HD was observed,
      both at the residue and the molecular level, with increasingly denaturing
      conditions. The absence of a co-operative transition could result from the
      denatured state ensemble progressing through a series of intermediates or from a
      more general slide (second-order transition) from the compact form under native
      conditions to the more extended at highly denaturing conditions. In either case,
      the starting point for folding under native conditions is highly structured and
      already poised to adopt the native structure.

PMID- 14583195
TI  - Unfolding mechanics of multiple OspA substructures investigated with single
      molecule force spectroscopy.
AB  - We investigated mechanical unfolding of Borrelia burgdorferi outer surface
      protein A (OspA), a Lyme disease antigen containing a unique single-layer beta
      sheet, with atomic force microscopy (AFM). We mechanically stretched a monomeric
      unit, rather than a tandem repeat, by pulling it from its N and C-terminal
      residues without using intervening polymer as a spacer. We detected two peaks in
      the force-extension profile before the final rupture of a fully extended
      polypeptide, which we interpreted as unfolding of multiple substructures in OspA.
      The double-peaked unfolding curves are consistent with results of previous
      thermodynamic studies showing two cooperative units in OspA. The mechanical
      unfolding processes were reversible, and the two substructures refolded within
      one second. Mutations near the boundary of the two thermodynamic cooperative
      units reduced the height of the first unfolding peak to undetectable levels and
      marginally affected the second one, indicating that the boundary between the two
      mechanical substructures is related to that previously assigned between the
      thermodynamic cooperative units. Based on a "worm-like chain" analysis of our AFM
      data, we propose a model for mechanical unfolding of OspA, where nearly a half of
      the chain is stretched with minimal resistive force, followed by sequential
      breakdown of C-terminal and N-terminal substructures. Based on these results, we
      discuss similarities and differences between mechanical and thermodynamic
      unfolding reactions of OspA. This work demonstrates that AFM study of monomeric
      proteins can elucidate details of the intramolecular mechanics of protein
      substructures.

PMID- 14583196
TI  - pH-dependent amyloid and protofibril formation by the ABri peptide of familial
      British dementia.
AB  - The ABri is a 34 residue peptide that is the major component of amyloid deposits
      in familial British dementia. In the amyloid deposits, the ABri peptide adopts
      aggregated beta-pleated sheet structures, similar to those formed by the Abeta
      peptide of Alzheimer's disease and other amyloid forming proteins. As a first
      step toward elucidating the molecular mechanisms of the beta-amyloidosis, we
      explored the ability of the environmental variables (pH and peptide
      concentration) to promote beta-sheet fibril structures for synthetic ABri
      peptides. The secondary structures and fibril morphology were characterized in
      parallel using circular dichroism, atomic force microscopy, negative stain
      electron microscopy, Congo red, and thioflavin-T fluorescence spectroscopic
      techniques. As seen with other amyloid proteins, the ABri fibrils had
      characteristic binding with Congo red and thioflavin-T, and the relative amounts
      of beta-sheet and amyloid fibril-like structures are influenced strongly by pH.
      In the acidic pH range 3.1-4.3, the ABri peptide adopts almost exclusively random
      structure and a predominantly monomeric aggregation state, on the basis of
      analytical ultracentrifugation measurements. At neutral pH, 7.1-7.3, the ABri
      peptide had limited solubility and produced spherical and amorphous aggregates
      with predominantly beta-sheet secondary structure, whereas at slightly acidic pH,
      4.9, spherical aggregates, intermediate-sized protofibrils, and larger-sized
      mature amyloid fibrils were detected by atomic force microscopy. With aging at pH
      4.9, the protofibrils underwent further association and eventually formed mature
      fibrils. The presence of small amounts of aggregated peptide material or seeds
      encourage fibril formation at neutral pH, suggesting that generation of such
      seeds in vivo could promote amyloid formation. At slightly basic pH, 9.0,
      scrambling of the Cys5-Cys22 disulfide bond occurred, which could lead to the
      formation of covalently linked aggregates. The presence of the protofibrils and
      the enhanced aggregation at slightly acidic pH is consistent with the behavior of
      other amyloid-forming proteins, which supports the premise that a common
      mechanism may be involved in protein misfolding and beta-amyloidosis.

PMID- 14583197
TI  - "Acceptor-donor-acceptor" motifs recognize the Watson-Crick, Hoogsteen and Sugar
      "donor-acceptor-donor" edges of adenine and adenosine-containing ligands.
AB  - Nucleotides are among the most extensively exploited chemical moieties in nature
      and, as a part of a handful of different protein ligands, nucleotides play key
      roles in energy transduction, enzymatic catalysis and regulation of protein
      function. We have previously reported that in many proteins with different folds
      and functions a distinctive adenine-binding motif is involved in the recognition
      of the Watson-Crick edge of adenine. Here, we show that many proteins do have
      clear structural motifs that recognize adenosine (and some other nucleotides and
      nucleotide analogs) not only through the Watson-Crick edge, but also through the
      sugar and Hoogsteen edges. Each of the three edges of adenosine has a donor
      acceptor-donor (DAD) pattern that is often recognized by proteins via a
      complementary acceptor-donor-acceptor (ADA) motif, whereby three distinct
      hydrogen bonds are formed: two conventional N-H...O and N-H...N hydrogen bonds,
      and one weak C-H...O hydrogen bond. The local conformation of the adenine-binding
      loop is betabetabeta or betabetaalpha and reflects the mode of nucleotide
      binding. Additionally, we report 21 proteins from five different folds that
      simultaneously recognize both the sugar edge and the Watson-Crick edge of
      adenine. In these proteins a unique beta-loop-beta supersecondary structure
      grasps an adenine-containing ligand between two identical adenine-binding motifs
      as part of the betaalphabeta-loop-beta fold.

PMID- 14583198
TI  - Structural context of exons in protein domains: implications for protein
      modelling and design.
AB  - Intron boundaries were extracted from genomic data and mapped onto single-domain
      human and murine protein structures taken from the Protein Data Bank. A first
      analysis of this set of proteins shows that intron boundaries prefer to be in non
      regular secondary structure elements, while avoiding alpha-helices and beta
      strands. This fact alone suggests an evolutionary model in which introns are
      constrained by protein structure, particularly by tertiary structure contacts. In
      addition, in silico recombination experiments of a subset of these proteins
      together with their homologues, including those in different species, show that
      introns have a tendency to occur away from artificial crossover hot spots.
      Altogether, these findings support a model in which genes can preferentially
      harbour introns in less constrained regions of the protein fold they code for. In
      the light of these findings, we discuss some implications for protein modelling
      and design.

PMID- 14583199
TI  - Structural determinants of metal specificity in the zinc transport protein ZnuA
      from synechocystis 6803.
AB  - A number of bacterial metal transporters belong to the cluster 9 family of ABC
      transporters. The residues in the periplasmic domain thought to be involved in
      metal binding seem highly conserved and yet the transporters have varying metal
      specificity. To solve this seeming paradox and ascertain how metal specificity is
      exacted, the structure of ZnuA, the periplasmic domain of a zinc transporter from
      Synechocystis 6803, has been determined to a resolution of 1.9A. In previously
      determined structures of homologous proteins, four residues chelate the bound
      metal. From sequence alignments of the cluster 9 metal transporters, the fourth
      residue in this metal-binding site, an aspartate, is also present in the
      appropriate position in the ZnuA sequence. However, this result is misleading,
      since our structural data indicate that zinc binds via only three histidine
      residues and the aspartate is replaced by a large hydrophobic cavity. We propose
      that ZnuA binds zinc over manganese by providing only three ligating residues.
      ZnuA has a highly charged and mobile loop that protrudes from the protein in the
      vicinity of the metal-binding site. Similar loops are found in other types of
      zinc transporters but not manganese transporters. Therefore, we propose that the
      function of this domain is to act as a zinc chaperone to facilitate acquisition.
      Therefore, while Mn2+ transporters can bind Zn2+ in vitro they may not be able to
      acquire it in vivo without this structure because of the low concentration of
      free Zn2+.

PMID- 14583200
TI  - A further simplification of the revised physical adsorption (RPA) model.
AB  - We present a further simplification of the essentially parameter-free revised
      physical adsorption model (K. Agashe, J.R. Regalbuto, J. Colloid Interface Sci.
      185 (1997) 174) in this paper. It has been discovered that a physical adsorption
      model describing the uptake of various metal complexes from aqueous solutions
      onto oxide surfaces can most accurately simulate experimental data when the model
      contains only a coulombic energy term, and not a solvation energy term. The
      results of the simulation for cobalt/silica, chloroplatinic acid (CPA)/alumina,
      and tetraamonium platinate (TAP)/alumina and silica are presented here. A
      reasonable justification for the omission of this term is that solvation effects
      are negligible when adsorbing metal complexes retain one or more hydration
      sheaths.

PMID- 14583201
TI  - The distribution of toluene in intercalation complexes of a vermiculite and alkyl
      trimethylammonium bromides.
AB  - Neutron diffraction and isotopic labeling have been used to determine the
      distribution of toluene sorbed into the interlamellar space of complexes of
      vermiculite with alkyl trimethylammonium bromide complex of alkyl chain lengths
      C(12), C(14), and C(16) and in a mixed C(12)/C(16) complex. The toluene remains
      in a liquid-like form and fills and swells the interlamellar space space up to a
      point where there remains a small amount of overlap of the alkyl chains of the
      surfactant. If the complex is between vermiculite and one surfactant only this
      results in the toluene concentration being reduced in the center of the
      interlamellar space, with maxima on either side. On the other hand, in a complex
      of mixed-length surfactants, the toluene distribution reaches its maximum at the
      center of the interlamellar space.

PMID- 14583202
TI  - Measurement of the kinetic rate constants for the adsorption of superspreading
      trisiloxanes to an air/aqueous interface and the relevance of these measurements
      to the mechanism of superspreading.
AB  - Super-spreading trisiloxane surfactants are a class of amphiphiles which consist
      of nonpolar trisiloxane headgroups ((CH3)3-Si-O)2-Si(CH3)(CH2)3-) and polar parts
      composed of between four and eight ethylene oxides (ethoxylates, -OCH2CH2-).
      Millimeter-sized aqueous drops of trisiloxane solutions at concentrations well
      above the critical aggregate concentration spread rapidly on very hydrophobic
      surfaces, completely wetting out at equilibrium. The wetting out can be
      understood as a consequence of the ability of the trisiloxanes at the advancing
      perimeter of the drop to adsorb at the air/aqueous and aqueous/hydrophobic solid
      interfaces and to reduce considerably the tensions of these interfaces, creating
      a positive spreading coefficient. The rapid spreading can be due to maintaining a
      positive spreading coefficient at the perimeter as the drop spreads. However, the
      air/aqueous and solid/aqueous interfaces at the perimeter are depleted of
      surfactant by interfacial expansion as the drop spreads. The spreading
      coefficient can remain positive if the rate of surfactant adsorption onto the
      solid and fluid surfaces from the spreading aqueous film at the perimeter exceeds
      the diluting effect due to the area expansion. This task is made more difficult
      by the fact that the reservoir of surfactant in the film is continually depleted
      by adsorption to the expanding interfaces. If the adsorption cannot keep pace
      with the area expansion at the perimeter, and the surface concentrations become
      reduced at the contact line, a negative spreading coefficient which retards the
      drop movement can develop. In this case, however, a Marangoni mechanism can
      account for the rapid spreading if the surface concentrations at the drop apex
      are assumed to remain high compared to the perimeter so that the drop is pulled
      out by the higher tension at the perimeter than at the apex. To maintain a high
      apex concentration, surfactant adsorption must exceed the rate of interfacial
      dilation at the apex due to the outward flow. This is conceivable because, unlike
      that at the contact line, the surfactant reservoir in the liquid at the drop
      center is not continually depleted by adsorption onto an expanding solid surface.
      In an effort to understand the rapid spreading, we measure the kinetic rate
      constants for adsorption of unaggregated trisiloxane surfactant from the sublayer
      to the air/aqueous surface. The kinetic rate of adsorption, computed assuming the
      bulk concentration of monomer to be uniform and undepleted, represents the
      fastest that surfactant monomer can adsorb onto the air/aqueous surface in the
      absence of direct adsorption of aggregates. The kinetic constants are obtained by
      measuring the dynamic tension relaxation as trisiloxanes adsorb onto a clean
      pendant bubble interface. We find that the rate of kinetic adsorption is only of
      the same order as the area expansion rates observed in superspreading, and
      therefore the unaggregated flux cannot maintain very high surface concentrations
      at the air/aqueous interface, either at the apex or at the perimeter. Hence in
      order to maintain either a positive spreading coefficient or a Marangoni
      gradient, the surfactant adsorptive flux needs to be augmented, and the direct
      adsorption of aggregates (which in the case of the trisiloxanes are bilayers and
      vesicles) is suggested as one possibility.

PMID- 14583203
TI  - Langmuir-Blodgett films of biopolymers: a method to obtain protein multilayers.
AB  - In this work, we present a methodology for choosing the best experimental
      conditions for transferring protein Langmuir films onto solid substrates. As an
      example of applying the proposed methodology, we used monolayers of the protein
      bovine serum albumin, which is a very stable protein and is of great interest in
      the development of immunosensors. Langmuir-Blodgett (LB) films of this protein,
      on different solid substrates, were obtained and characterized as a function of
      pH, surface pressure, temperature, and contact angle. The compressibility
      modulus, the spreading entropy, and the fraction of desorbed protein sections
      were used as control parameters to find these conditions. A careful analysis of
      these parameters shows that there is a window on the values of these experimental
      parameters in which the LB films are best formed. Our methodology can be applied
      to other biomacromolecules to find the best conditions to form LB films from
      isotherm measurements.

PMID- 14583205
TI  - Fluoride sorption and associated aluminum release in variable charge soils.
AB  - Fluoride sorption and related aluminum (Al) release are evaluated in two iron
      oxide-rich soils as a function of soil depth, composition, and physical-chemical
      properties and potential mechanisms of fluoride-surface interaction are
      suggested. Measured Al concentrations at equilibrium fluoride sorption,
      reflective of the net balance between Al dissolution and sequestration of the
      released Al by the solid phase, suggest net fluoride-assisted dissolution of Al
      bearing amorphous and crystalline soil minerals. Strikingly, soils of similar
      depth and horizonation from the same soil order but of distinct soil series
      exhibited markedly different susceptibility to Al loss in the presence of
      fluoride, possibly a combined result of differences in the mechanism of fluoride
      sorption, soil mineralogy, reactivity of the surficial Al and Fe, and soil
      solution chemistry. Fluoride sorption is strongly correlated with soil Al and Fe
      present as high-surface-area amorphous and crystalline oxide phases. Fluoride
      complexation to surficial Al and Fe ions via ligand exchange with surficial OH
      groups and water molecules appears to be the dominant sorption mechanism. At high
      dissolved fluoride concentrations (>7 mM), other mechanisms of fluoride retention
      including adsorption of AlF solution complexes, entrapment in the interparticle
      pore fluid, and precipitation into solution and/or onto the soil surface are also
      likely.

PMID- 14583204
TI  - Contribution of acidic amino residues to the adsorption of peptides onto a
      stainless steel surface.
AB  - The role of the acidic amino acid residues in the adsorption of peptides/proteins
      onto stainless steel particles was investigated using a peptide fragment from
      bovine beta-lactoglobulin, Thr-Pro-Glu-Val-Asp-Asp-Glu-Ala-Leu-Glu-Lys (T5
      peptide), which has a high affinity to a stainless steel surface at acidic pHs,
      and its mutant peptides substituted with different numbers of acidic amino acid
      residues. The adsorption behavior of the mutant peptides as well as the T5
      peptide were studied at pH 3 with respect to concentration and ionic strength
      dependencies and the reversibility of the adsorption process. The behavior of the
      peptides was generally characterized as two distinct irreversible adsorption
      modes, Mode I and Mode II. In Mode I, the amounts adsorbed lay on the ordinate at
      zero equilibrium concentration in the solution, while in Mode II, the amount
      adsorbed increased with increased equilibrium concentration. The area occupied by
      the peptides was predicted by molecular mechanics and molecular dynamics. The
      state of the peptides, when adsorbed, was investigated using FT-IR analysis. The
      FT-IR analyses revealed that the side carboxylic groups of the peptides adsorbed
      on the stainless steel surface were ionized, while they were unionized in the
      solution at pH 3. Thus, the interactions between the carboxylic groups of the
      peptide and the stainless steel surface can be considered to be largely
      electrostatic. The peptide having four acidic amino acid residues took a maximum
      adsorbed amount, the reason for which is discussed.

PMID- 14583206
TI  - Fractal behavior and scaling law of hydrophobic silica in polyol.
AB  - This article examines the rheological properties of a system composed of polyol
      and colloidal silica. Three types of nanosized silicas with hydrophilic and
      hydrophobic surfaces were studied: A200 with OH surface groups, R974 with CH(3)
      surface groups, and R805, which is grafted with a C(8)H(17) alkyl chain.
      Rheometric measurements showed that the dispersions of R805 silicas have a yield
      stress at low volume fraction, unlike the R974 and A200 silicas. The plastic
      behavior of the hydrophobic silicas was quantified by a yield stress sigma(0) and
      an elastic modulus G'. It is observed that these parameters follow scaling laws
      as a function of the volume fraction of silica introduced, in the form sigma(0)
      approximately phi(v)(2.9+/-0.2), G' approximately phi(v)(4.1+/-0.3). Static light
      scattering (SLS) and small angle neutron scattering (SANS) measurements show a
      fractal arrangement with a fractal dimension D=1.8 ranging from elementary
      particles of about 32 nm to aggregates measuring about 6 mum. Correlations were
      established between the theoretical scaling laws and the experimental scaling
      laws determined by rheometric measurements. The fractal structure observed in
      this system is explained by the attractive physical interaction of the octyl
      chains between the silica particles. Contrary to what has been observed in the
      past by Khan and Zoeller (J. Rheol. 37 (1993) 1225), the lower molecular weight
      of the polyol studied here, which has a shorter chain length, allows direct
      bridging of two separate silicates though alkyl chains, giving rise to the
      formation of a 3D gel network at volume fractions as low as phi(v)=2.2%.

PMID- 14583207
TI  - Synthesis of cross-linked core-shell polymer particles by free-radical dispersion
      copolymerization of 4-vinylpyridine with polystyrene macromonomers in nonaqueous
      media.
AB  - Cross-linked core-shell polymer particles were synthesized by free-radical
      dispersion copolymerization of 4-vinylpyridine (4VP) and various kinds of cross
      linking reagents with methacryloyl-terminated polystyrene (PS) macromonomers in
      nonaqueous media such as 1,4-dioxane and cyclohexane. Well-defined particles were
      obtained by copolymerization of 4VP with ethylene glycol dimethacrylate (EGDM) in
      a dioxane medium. The particle diameters (D(n)=40-990 nm) decreased drastically
      both with increasing the feed concentration ratio of macromonomer to 4VP, [PS
      M]/[4VP], and with increasing molecular weight of PS-M macromonomers. The
      particle size distribution (D(w)/D(n)) was in the range 1.02-1.10. PS-M
      macromonomers acted not only as comonomers but also as stabilizers. The particle
      diameters obtained in dioxane were smaller than those obtained in cyclohexane.
      Thus, we observed a tendency to smaller particle size as the media became more
      soluble for PS-M macromonomer.

PMID- 14583208
TI  - The nature of the structural gradient in epoxy curing at a glass fiber/epoxy
      matrix interface using FTIR imaging.
AB  - The curing process of an epoxide system was studied at the interface formed
      between a silane-coated glass fiber and an epoxy matrix. The gradient in the
      structure of the epoxy resin as a result of the cure process at the fiber/matrix
      interfacial region was monitored by FTIR imaging. For comparison, the epoxy
      curing at the interface formed between the epoxy resin and (a) an uncoated glass
      fiber and (b) a polyorganosiloxane (obtained from the silane used for the glass
      fiber coating) were also monitored. Chemically specific images of the OH and the
      H-N-H groups near the interface region were obtained. These images suggest that
      there is a chemical gradient in the structure of the matrix from the fiber
      surface to the polymer bulk due to different conversions. The basis of the
      different kinetics of the curing reactions is a result of amino group
      inactivation at the interface. This deactivation translates into an off
      stoichiometry of the reaction mixture, which is a function of the distance from
      the surface of the glass fiber.

PMID- 14583209
TI  - Surface properties of poly(acrylonitrile) (PAN) precipitation polymerized in
      supercritical CO2 and the influence of the molecular weight.
AB  - In this paper, the surface properties, e.g., the total surface free energy and
      the related Lifshitz-van der Waals and Lewis acid-base components, of
      polyacrylonitrile (PAN) precipitation polymerized in supercritical CO(2) have
      been characterized. Moreover, the influence of molecular weight varying has been
      also investigated. Results show that the surface properties of PAN resulting from
      supercritical CO(2) are different from those obtained by the conventional method.
      Of these data, one important finding is that the supercritical CO(2) PAN seems to
      decrease the surface free energy with the increased molecular weight. Based on
      previous recorded NMR spectra of this PAN and especially compared to commercial
      PAN, such phenomena are discussed and ascribed to an increase of the H-bonds and
      a reduction of the isotacticity in the supercritical CO(2) condition for PAN.

PMID- 14583210
TI  - Probing protein hydration and aging of food materials by the magnetic field
      dependence of proton spin-lattice relaxation times.
AB  - Most cheeses can be considered as solid emulsions of milk fat in a matrix of
      water and proteins. Regions of each of the phases can be liquid during processing
      and maturation. Identifying these regions and monitoring changes in them is
      important as a prelude to controlling the structure of the final cheese. We
      concentrate on the behavior of water in the vicinity of proteins as a function of
      cheese aging. Our method utilizes nuclear magnetic relaxation dispersion (NMRD)
      associated with the frequency dependence of water spin-lattice relaxation rates
      using the field cycling NMR technique. This method provides insight into the
      dynamical behavior of water molecules on a very large time scale. Moreover, we
      can distinguish between molecular motion in bulk and motion in the vicinity of a
      source of relaxation, such as proteins. A fit of our dispersion data using a
      theory developed by J.-P. Korb and R.G. Bryant (J. Chem. Phys. 115 (2001) 23)
      allowed us to determine the degree of hydration of proteins as a function of
      aging. In particular, we find that protein hydration increases with ripening.

PMID- 14583211
TI  - Organo-modified cationic silica nanoparticles/anionic polymer as flocculants.
AB  - The synthesis of quaternized silica nanoparticles and its application to fine
      clay flocculation were investigated. N-trimethoxysilylpropyl-N,N,N
      trimethylammonium chloride was used as a cationic reagent to introduce quaternary
      amine groups onto the surfaces of silica nanoparticles via the formation of
      covalent bonds between the methoxy groups of the cationic reagents and the
      silanol groups in the silica surface. The zeta potential, zeta, and charge
      density of the silica particles modified under various reaction conditions were
      determined. Dynamic clay flocculation experiments using a photometric dispersion
      analyzer (PDA) showed that the cationic silica alone contributed little to the
      flocculation. However, the cationic silica, in conjunction with an anionic
      polymer of high M(w) and low charge density, led to a significant improvement in
      the flocculation of fine clay particles. The mechanism of flocculation was
      explored by a systematic investigation of interaction between cationic silica and
      anionic polymers as well as of their adsorption behavior on clay surfaces. The
      influence of factors such as pH and electrolyte concentration on clay
      flocculation was also investigated.

PMID- 14583212
TI  - Measurement of mobility of adsorbed colloids by lateral force microscopy.
AB  - The surface mobility of colloidal latex particles adsorbed on mica was measured
      by moving the particles with an AFM tip in the lateral force microscopy mode. The
      same particle was repeatedly scanned while the normal force was gradually
      increased, until the particle was displaced from its location on the substrate.
      The lateral (friction) force curve obtained for that scan was then used to
      determine the force needed to displace the particle. The data accumulated for
      approximately 100 particles indicate a wide distribution in the lateral force
      required. However, the data show that the mean lateral force is proportional to
      the particle diameter, with the effect of electrostatic interactions on the
      mobility of adsorbed particles seen to be weak. These results are consistent with
      classical theories of friction in macroscopic systems.

PMID- 14583213
TI  - Size distribution of colloidal silica in sodium silicate solutions investigated
      by dynamic light scattering and viscosity measurements.
AB  - Three types of aqueous sodium silicate solutions characterized by molar
      SiO(2):Na(2)O ratios of 2.2, 3.3, and 3.9 were investigated by dynamic light
      scattering and viscosity measurements. The solutions were prepared by diluting
      concentrated commercial products to SiO(2) content between 0.5 and 15 wt%.
      Dynamic light scattering (DLS) was used for the investigation of size
      distributions of colloids immediately after dilution. At least three size classes
      of colloidal particles were detected, which exist in parallel in the solutions.
      The respective radii are 0.4 to 0.6 nm, 2.5 to 13 nm, and 75 to 85 nm. The larger
      colloids dominate the mass distribution, whereas the smaller colloids control the
      surface area of the colloidal fraction. Material properties such as pH,
      viscosity, refractive index, and density were measured as a function of dilution.
      The evaluation of the viscosity data indicated that the colloids have a lower
      density than dense amorphous silica. Aging effects could be suppressed by
      measuring within 1 h after dilution.

PMID- 14583214
TI  - Visualizing transport processes at liquid-liquid interfaces--the application of
      laser-induced fluorescence.
AB  - Modeling of liquid-liquid extraction processes involves the concentration of the
      extracted component directly at the interface. Currently, only very few and
      specialized methods are available for the direct measurement of these
      concentrations. Therefore a new, fluorescence-based measurement system with a
      high spatial resolution and a broad application spectrum was developed and
      tested. The detection principle is based on the use of fluorescent dyes excited
      by an argon ion laser. The intensity of the emitted light is dependent on the
      concentration of the extracted component in the very near surroundings of the
      dye. This intensity distribution is reproduced by an optical, microscope-based
      system onto a highly sensitive camera with a spatial resolution of 1 mum. This
      distribution is converted into a concentration profile at the interface using a
      calibration function and digital image processing routines. Measurements were
      performed in a commonly used stirred two-phase reactor modified to meet the
      requirements of an optical measurement system. It was shown that the
      concentration profiles at moving and nonmoving interfaces could be visualized
      with a resolution of 1 mum. The profiles formed at the interface differ
      significantly according to the kinetic of the used extraction system and the flow
      profiles in the reactor and can be used for further modeling of the extraction
      processes.

PMID- 14583215
TI  - Photocatalytic activity of rutile-anatase coupled TiO2 particles prepared by a
      dissolution-reprecipitation method.
AB  - Rutile TiO(2) particles were partly dissolved into aqueous solutions of
      H(2)SO(4), and the Ti(4+) ions were reprecipitated by adding NH(3) aq. Rutile
      anatase coupled TiO(2) particles were prepared by heating the solid recovered
      after centrifugation of the suspension. The content of anatase (c(A), wt%) could
      be controlled arbitrarily by changing the dissolved amount of rutile. The
      photocatalytic activity for the gas-phase oxidation of acetaldehyde was
      evaluated. The first-order rate constant, k, strongly depended on both c(A) and
      heating temperature (T(c)), increasing with an increase in T(c) at T(c)</=800
      degrees C. The sample with c(A)=0.5 wt% prepared at T(c)=800 degrees C exhibited
      a much higher level of activity (k=0.94 h(-1)m(-2)) than those of pure rutile
      (k=0.08 h(-1)m(-2)) and anatase (k=0.34 h(-1)m(-2)). This remarkable enhancing
      effect was explained mainly in terms of photoinduced interfacial electron
      transfer from anatase to rutile.

PMID- 14583216
TI  - Studies on platinum-promoted sulfated zirconia alumina: effects of pretreatment
      environment and carrier gas on n-butane isomerization and benzene alkylation
      activities.
AB  - A series of platinum-promoted sulfated zirconia alumina catalysts (SZA) with
      different amounts of platinum (0.5, 1, and 2 wt%) were synthesized. Two other
      catalysts were prepared by mechanically mixing different proportions of the Al
      promoted sulfated zirconia with Pt/Al(2)O(3). The 650 degrees C calcined
      catalysts were characterized by N(2) adsorption/desorption (BET), TPR, and TPD
      analysis. Butane isomerization activity of the catalysts was studied at 270
      degrees C, varying the pretreatment environment and carrier gases. Though the
      textural properties of the catalysts did not change significantly with platinum
      loading, the maximum surface area of 116 m(2)/g was exhibited by the catalyst
      with 1 wt% Pt loading. Under the studied reaction conditions, the air-pretreated
      catalysts (sulfated zirconia alumina (SZA) and platinated SZA) showed higher n
      butane conversion than the N(2)-pretreated catalyst. However, nitrogen was a
      better carrier gas than H(2), CO(2) or air, and CO(2) and air deactivated the
      catalyst very fast. Unlike the platinated SZA catalysts, the mechanically mixed
      catalysts showed an induction phenomenon. A redox mechanism is suggested for
      butane isomerization over these catalysts. The catalyst SZA was also found to be
      active for alkylation of benzene with isopropanol, which gave 93% selectivity
      toward cumene.

PMID- 14583217
TI  - Structural effects in the kinetic behavior of the monomer-dimer surface reaction
      over nondeterministic fractal surfaces.
AB  - A study is made of the segregation effect of adsorbed species related to the
      inner structure of two bidimensional adsorbent fractals, the incipient
      percolation cluster (IPC) and the backbone of the IPC, and their connection with
      the rate-determining step of the kinetic mechanism of the monomer-dimer (MD)
      surface reaction on those fractals. Production, R(AB), is proportional to the
      concentration of A in the gas phase y(A) and to the fraction of vacant
      superficial sites x(E) (R(AB)=y(A)x(E)), and it is shown that adsorption of the
      monomer is the rate-controlling step of the reaction mechanism.

PMID- 14583218
TI  - Stability of a fluid-fluid interface in a biconical pore segment.
AB  - Pore networks that include biconical pore segments are frequently used to model
      two-phase flow. In this work, we describe in detail the displacement of a fluid
      fluid interface in such a pore segment. We assume sharp edges in the throat,
      inlet, and outlet of the pore segment to be the limiting cases of round edges,
      the radii of which vanish. We account for interfacial and lineal tensions that
      cause nonconstant contact angles. For zero lineal tension, we provide analytical
      solutions for flow induced by changing infinitesimally slowly either capillary
      pressure or the volume of one fluid. In diverging and converging cones, the
      common line among the two fluids and the solid phase slides while it is pinned in
      the throat, inlet, and outlet. We observe hysteresis within the pore segment, and
      drainage entry pressures deviate from prior work.

PMID- 14583219
TI  - Characteristics of activated carbons prepared from pistachio-nut shells by
      physical activation.
AB  - Activated carbons were prepared from pistachio-nut shells, which are one type of
      lignocellulosic material, by a two-step physical method. The effects of the
      preparation variables on the activated carbon pore structure were studied,
      followed by the optimization of these operating parameters. It was found that the
      activation temperature and dwell time are the important parameters that affect
      the characteristics of the activated carbons obtained. The effects of CO(2) flow
      rate and heating rate during activation were also studied. Under the experimental
      conditions used, the optimum conditions to prepare activated carbons with high
      surface area and pore volume were identified. The microstructure of the activated
      carbons prepared was examined by scanning electron microscopy while the Fourier
      transform infrared spectra showed the changes in the surface functional groups
      produced during the different preparation stages.

PMID- 14583220
TI  - Interfacial tension and interfacial profiles: an equation-of-state approach.
AB  - A quasi-thermodynamic approach of inhomogeneous systems is used for modeling the
      fluid-fluid interface. It is based on the recently introduced QCHB (quasi
      chemical hydrogen bonding) equation-of-state model of fluids and their mixtures,
      which is used for the estimation of the Helmholtz free energy density difference,
      Deltapsi(0), between the system with interface and another system of the same
      constitution but without interface. Consistent expressions for the interfacial
      tension and interfacial profiles for various properties are presented. The
      interfacial tension is proportional to the integral of Deltapsi(0) along the full
      height of the system, the proportionality constant being equal to 1, when no
      density gradient contributions are taken into consideration, 2, when the Cahn
      Hilliard approximation is adopted, and 4, when the full density gradient
      contributions are taken into consideration. A satisfactory agreement is obtained
      between experimental and calculated surface tensions. Extension of the approach
      to mixtures is examined along with the associated problems for the numerical
      calculations of the interfacial profiles. A new equation is derived for the
      chemical potentials in the interfacial region, which facilitates very much the
      calculation of the composition profiles across the interface.

PMID- 14583221
TI  - Liquid-vapor isotherm in a closed single-component system with curved interfaces.
AB  - A thermodynamic model to obtain the radius of bubbles or droplets in a single
      component system for a given temperature, total volume, and phase distribution is
      developed. The general formulation of the model includes bubbles or droplets in
      the form of spheres, truncated spheres on a flat solid surface or inside conical
      walls. In these three geometries the liquid-vapor curvature radius is positive
      but in the case of conical walls it can be also negative. States with different
      dispersed-phase distributions are compared using the total free energy of the
      system. When the curvature radius is positive, it has a minimum nonvanishing
      value and the occurrence of the Ostwald ripening is energetically favorable. On
      the other hand, when the curvature radius is negative, it is energetically more
      favorable to find the dispersed phase even in the expected single-phase region,
      and the occurrence of an anti-ripening phenomenon. The PV isotherms obtained from
      the model and the applicability of the results to the nucleation process are
      discussed.

PMID- 14583222
TI  - Liquid-vapor isotherm in a closed single-component system with droplets or
      bubbles in smooth crevices.
AB  - A thermodynamic model in order to study a single-component system where droplets
      or bubbles are inside smooth crevices is presented. Liquid-vapor interface
      curvature radius can change its sign as the droplet or bubble volume change. The
      results suggest that there is always dispersed phase inside smooth crevices of
      microscopic dimensions, even in the expected single-phase region. Thus, the
      occurrence of an anti-ripening phenomenon is predicted from a microscopic point
      of view; meanwhile the occurrence of a ripening phenomenon is energetically
      favorable at a macroscopic scale. The relevance of these results on the
      heterogeneous nucleation process is analyzed.

PMID- 14583223
TI  - Unusual wetting dynamics of aqueous surfactant solutions on polymer surfaces.
AB  - Static and dynamic contact angles of aqueous solutions of three surfactants-
      anionic sodium dodecyl sulfate (SDS), cationic dodecyltrimethylammonium bromide
      (DTAB), and nonionic pentaethylene glycol monododecyl ether (C(12)E(5))--were
      measured in the pre- and micellar concentration ranges on polymer surfaces of
      different surface free energy. The influence of the degree of substrate
      hydrophobicity, concentration of the solution, and ionic/nonionic character of
      surfactant on the drop spreading was investigated. Evaporation losses due to
      relatively low humidity during measurements were taken into account as well. It
      was shown that, in contrast to the highly hydrophobic surfaces, contact angles
      for ionic surfactant solutions on the moderately hydrophobic surfaces strongly
      depend on time. As far as the nonionic surfactant is considered, it spreads well
      over all the hydrophobic polymer surfaces used. Moreover, the results obtained
      indicate that spreading (if it occurs) in the long-time regime is controlled not
      only by the diffusive transport of surfactant to the expanding liquid-vapor
      interface. Obviously, another process involving adsorption at the expanding solid
      liquid interface (near the three-phase contact line), which goes more slowly than
      diffusion, has to be active.

PMID- 14583224
TI  - Numerical analysis of capillarity in packed spheres: planar hexagonal-packed
      spheres.
AB  - General solutions of the capillary pressure for liquids as a function of contact
      angle and volume in planar close-packed spheres have been calculated numerically
      using Surface Evolver software. Applied pressure differences between liquid and
      vapor result in undulating (puckered) menisci exhibiting anticlastic curvature in
      the narrower spaces near particle contacts. The corresponding capillary pressures
      exhibit maxima with infiltration volume (minima with drainage), corresponding to
      critical pressures for engulfment of the spheres by the liquid (vapor). The
      analysis also reveals the formation of residual pendular rings of the wetting
      phase around particle contacts. Pendular ring formation is explored further by
      analyzing hexagonally packed spheres separated by 1/10 their radius. The results
      are discussed relative to the wide range of approximate solutions available in
      the literature.

PMID- 14583225
TI  - Adsorption kinetics of surfactant mixtures from micellar solutions as studied by
      maximum bubble pressure technique.
AB  - The adsorption kinetics of micellar solutions of anionic/cationic SDS/DATB
      mixtures with mixing ratios of 10/1 and 10/2, respectively, are studied
      experimentally by means of the maximum bubble pressure method. For long
      adsorption times the adsorption of the highly surface-active anionic/cationic
      complex leads to a decrease of dynamic surface tension in comparison to the
      single SDS system. However, the situation is the reverse for short adsorption
      times where the dynamic surface tension is increased by addition of the cationic
      surfactant, although the overall concentration is increased. This unexpected
      behavior is explained by partial solubilization of free SDS molecules into
      micelles formed by SDS/DTAB complexes. With increasing overall concentration,
      when eventually the CMC of SDS is reached, the anionic/cationic complex itself is
      solubilized by SDS micelles. Finally, no complex micelles, which for their part
      can solubilize an excess of SDS molecules, are present. Hence, the dynamic
      properties of the solution are no longer influenced by the depletion of SDS
      molecules and the mixture tends to behave like a pure SDS solution.

PMID- 14583226
TI  - Shape relaxation of an elongated viscous drop.
AB  - The shape relaxation of a distorted viscous drop suspended in a quiescent
      immiscible liquid is analyzed in the creeping flow limit. The shape of the drop
      is axisymmetric, but otherwise arbitrary. The relaxation process is assumed to be
      driven by a constant interfacial tension and rate-limited by the Newtonian
      viscosities of the dispersed and continuous phases. For analysis, a least squares
      technique is developed which, compared to the more common boundary integral
      methods, is simpler to implement and especially suited for systems where one
      liquid is much more viscous than the other (i.e., when the viscosity ratio
      lambda, defined as the ratio of the dispersed to continuous phase viscosities,
      approaches either zero or infinity). To demonstrate the validity of the proposed
      least squares technique, its results are shown to agree well with boundary
      integral calculations for moderate values of lambda, and with experimental data
      when lambda is much larger than unity (approximately 10(6)). Predictions at
      infinite viscosity ratio--the regime in which the least squares technique is most
      useful--are then used to evaluate interfacial tensions associated with a system
      of practical importance, namely, the dispersion of heavy crude oil in an aqueous
      environment. This amounts to a novel and accurate technique for determining
      interfacial tensions--especially those of low values (1 mN/m or less)--between
      density-matched liquids where at least one of the phases is highly viscous. The
      experimental part of this study involves the use of suction pipettes to
      manipulate the shapes of individual micrometer-sized droplets, thus avoiding the
      need for complex flow-generating devices to create drop deformations.

PMID- 14583227
TI  - Counterion exchange selectivity coefficients at water-in-oil microemulsion
      interface.
AB  - The counterion binding at a water/Aerosol-OT (AOT)/heptane microemulsion
      interface was treated in the context of the pseudo-phase ion exchange formalism.
      Two approaches were used to determine the selectivity coefficient for
      copper/sodium counterion binding at the AOT microemulsion interface: measurements
      of the Cu(II) concentration taken up by the reverse micelle in a Winsor II
      microemulsion system and steady-state emission quenching measurements of an
      anionic water-solubilized probe, the tris-(4,4'-dicarboxy-2,2'-bipyridine)
      ruthenium (II) ion. In addition, the selectivity coefficient for methyl
      viologen/sodium at the microemulsion surface was determined by the same
      photophysical technique. The value for copper (II)/sodium exchange (K(Cu/Na)) is
      1.1+/-0.3 and that for methyl viologen/sodium (K(MV/Na)) is 0.9+/-0.3. The
      results show that the pseudo-phase ion exchange model can be used to obtain the
      selectivity coefficient in a microemulsion system.

PMID- 14583228
TI  - Dynamic fluorescence microscopy as a feasible technique for estimating the
      diffusion coefficients of small particles in the presence of additives.
AB  - The Brownian motion of carboxylated polystyrene latex, labeled with fluorescent
      probe molecules, at low concentrations in aqueous solutions was investigated by
      dynamic fluorescence microscopy. For all three latex radii, i.e., 0.5, 0.265, and
      0.1 mum, the estimated diffusion coefficients correspond well with the
      theoretical predictions if thermal and electrostatic contributions are included
      in the discussions. It was also possible to discriminate latex interactions with
      an added polymer. Added polyethylene glycol showed no or very weak interaction
      with the latex until the polymer overlap concentration was reached, at which the
      formation of a polymer network slowed down the latex diffusion.
      Polyvinylpyrrolidone, on the other hand, had a more pronounced interaction with
      the polystyrene latex and slowed down the diffusion even at polymer
      concentrations in the ppm range. The overall conclusion is that fluorescence
      microscopy is a feasible method for the study of the dynamic behavior of small
      particles in solution.

PMID- 14583229
TI  - Physical organogels composed of amphiphilic block copolymers and 1,3:2,4
      dibenzylidene-D-sorbitol.
AB  - The 1,3:2,4-dibenzylidene-D-sorbitol (DBS) molecule is capable of self-organizing
      into nanoscale fibrils through intermolecular forces such as hydrogen bonding and
      pi interactions. At sufficiently high concentrations (typically less than
      approximately 2 wt%), the nanofibrils can form a network that promotes physical
      gelation of the matrix medium. Previous studies have investigated the mechanism
      of DBS-induced gelation and the features of DBS-containing gels in poly(ethylene
      glycol) (PEG) and poly(propylene glycol) (PPG). In this work, we examine the
      effect of adding DBS to a series of amphiphilic PPG-b-PEG-b-PPG triblock
      copolymers differing in composition and molecular weight. Dynamic rheological
      measurements reveal that the resultant gels are thermoreversible (i.e., they
      exhibit comparable mechanical properties before dissolution and after reformation
      under quiescent conditions), exhibiting a maximum in the elastic modulus (G') at
      temperatures near the gel dissolution (T(d)) and formation (T(f)) temperatures.
      Both T(d) and T(f) tend to increase with increasing DBS concentration and PPG
      content, and their difference decreases with increasing PPG fraction in the
      copolymer. The magnitude of G' is sensitive to copolymer composition and polymer
      identity at low DBS concentrations, but becomes polymer-independent as the DBS
      network saturates at concentrations in excess of approximately 1 wt%.

PMID- 14583230
TI  - Effect of the nature of the counterion on the interaction between cesium and
      tetraalkylammonium dodecylsulfates and poly(ethylene oxide) or
      poly(vinylpyrolidone).
AB  - The interaction between poly(ethylene oxide) or poly(vinylpyrrolidone) and cesium
      and tetraalkylammonium (tetramethyl to tetrabutyl ammonium) dodecylsulfate has
      been investigated by means of electrical conductivity measurements to determine
      the critical aggregation concentration (cac) of the surfactants in the presence
      of polymer. The cac values were compared to the values of the critical
      micellization concentration (cmc) of the surfactants in the absence of polymer.
      The value of the cac/cmc ratio increased with the radius of the counterion in the
      sequence:
      Na(+)<Cs(+)<tetramethylammonium(+)<tetraethylammonium(+)=tetrapropylammonium(+)=t
      trabutylammonium(+)=1.0. This result indicates that the strength of the
      interaction decreases upon increasing counterion radius. For the last three
      tetraalkylammonium ions the value cac/cmc=1 indicates the absence of interaction.
      The results are discussed in an attempt to gain a better understanding of the
      mechanism of formation of surfactant aggregates bound to water-soluble polymers
      such as poly(ethylene oxide) or poly(vinylpyrrolidone).

PMID- 14583232
TI  - The two faces of CNS inflammation: can we tell Dr. Jekyll from Mr. Hyde?

PMID- 14583231
TI  - Stable individual differences in physiological response to stressors:
      implications for stress-elicited changes in immune related health.
AB  - Stress reactivity refers to a stable individual difference in response to
      stressors. This article addresses three questions about reactivity: (1) Are
      cardiovascular, endocrine, and immune responses to acute laboratory stressors
      stable over time and across stressor tasks? (2) Are cardiovascular, endocrine,
      and immune reactors the same people? and (3) Are reactive people more vulnerable
      to stressor-induced effects on susceptibility to infectious disease? We conclude
      that for many individual indicators of physiological responsiveness to stressors
      there is moderate stability over time and across stressor tasks indicating the
      possible existence of underlying dispositional characteristics; the commonality
      of immune and cardiovascular and hormonal responses to stress depend on the
      nature of regulation of the immune response being assessed; reactivity appears to
      have implications for vulnerability to stressor-associated disease risk (stress
      by-reactivity interaction) in the natural environment, but the exact nature of
      this vulnerability is not as yet entirely clear.

PMID- 14583233
TI  - Natural killer cells do not mediate facial motoneuron survival after facial nerve
      transection.
AB  - The goal of the current study was to determine if natural killer (NK) cells
      mediate facial motoneuron (FMN) survival following injury. Wild-type (WT),
      perforin/recombinase activating gene-2 knockout (pfp/RAG-2 KO), and common gamma
      chain (gammac)/RAG-2 KO mice received a right facial nerve axotomy. In WT mice,
      FMN survival was 86+/-1.0% relative to the contralateral control side. In
      contrast, pfp/RAG-2 and gammac/RAG-2 KO mice exhibited significant decreases in
      FMN survival ( approximately 20% and approximately 30%, respectively), relative
      to WT. Reconstitution of pfp/RAG-2 and gammac/RAG-2 KO mice with normal NK cells
      alone, failed to restore FMN survival levels to those of WT, but did restore
      functional lytic activity against YAC-1 cells. Reconstitution of pfp/RAG-2 and
      gammac/RAG-2 KO mice with splenocytes, and pfp/RAG-2 KO mice with CD4+ T
      lymphocytes alone or in combination with NK cells, restored FMN survival levels
      to those of WT. Thus, NK cells appear to not be a component of immune cell
      mediated rescue of motoneurons from axotomy induced cell death.

PMID- 14583234
TI  - Social experience alters the response to social stress in mice.
AB  - Individual differences in the response to stressful stimuli have been documented
      in humans and in a variety of animal species. Recently, we demonstrated that
      social stress induced a state of glucocorticoid (GC) resistance in mouse
      splenocytes, however this response was highly variable among cage mates. Since
      these studies were conducted using inbred mice (C57BL/6), it was suggested that
      environmental factors were the source of this variability. The following study
      examined possible factors that may have contributed to the development of
      individual differences in the susceptibility of mice to social stress. First, the
      effect of rearing conditions was studied by comparing the development of GC
      resistance in mice reared in isolation or in groups. In addition, the effect of
      previous social experiences was studied in mice that were re-housed to facilitate
      the formation of new social hierarchies in the cages. The results indicated that
      isolation altered the behavior of the mice during the social stress, but did not
      affect the development of GC resistance in response to the stress. Re-housing and
      the resulting loss of social status increased the susceptibility of mice to the
      development of GC resistance following social stress. Together, these findings
      indicate that environmental factors, such as previous social experiences, may
      alter the susceptibility to the effects of future social stress in inbred mice.

PMID- 14583235
TI  - Asymmetrical modulation of interleukin-10 release in patients with intracerebral
      hemorrhage.
AB  - The brain modulates the immune system in an asymmetrical way. Intracerebral
      hemorrhage triggers IL-6 and IL-10 release into blood. We measured (using ELISA
      method) serum IL-6 and IL-10 in acute phase of intracerebral hemorrhage in 11
      patients with right hemisphere's hematoma and 15 patients with left hemisphere's
      hematoma. These patients did not differ significantly with respect to their age,
      size, and location of hematoma. IL-6 level was comparable in patients with left
      hematoma and patients with right hematoma, but patients with left hematoma had
      significantly higher level of IL-10 than patients with right hematoma. These
      results suggest that left and right hemisphere could modulate IL-10 release in
      different way.

PMID- 14583236
TI  - Neuropeptide specificity of prostaglandin E2-induced activation of splenic and
      renal sympathetic nerves in the rat.
AB  - Sympathetic activation occurs rapidly following intracerebroventricular (icv)
      injection of prostaglandin E2(PGE2). This study examined whether neuropeptides
      mediate PGE2-induced sympathetic nerve activation in urethane/chloralose
      anesthetized Sprague-Dawley rats. Animals were pretreated (20.0 microg, icv) with
      the following receptor antagonists; CRF ([D-Phe12,Nle21,38,Calpha-MeLeu37]CRF12
      41), AVP-V1 (Des-Gly-[Phaa1, D-Tyr(Et)2,Lys6,Arg8]-vasopressin), or OT (OT+V1,
      [d(CH2)5,Tyr(Me)2,Orn8]-vasotocin) followed 20 min later by PGE2 (2.0 microg,
      icv). Pretreatment with the CRF antagonist attenuated the increase in renal nerve
      activity induced by PGE2 when measured 10 and 30 min post-injection. PGE2-induced
      renal nerve activity was also inhibited at both time points by the AVP antagonist
      and, to a similar extent, the OT antagonist. The AVP antagonist did not effect
      splenic nerve responses to PGE2 whereas the CRF antagonist produced an incomplete
      and transient reduction in PGE2-induced activation of the splenic nerve. However,
      the OT antagonist completely blocked the activation of the splenic nerve after
      central injection of PGE2. ICV injections of AVP and OT produced immediate
      changes in splenic and renal nerve activity whereas CRF failed to alter the
      activity of either nerve in anesthetized or conscious animals. Thus, PGE2 acts
      through neuropeptide-specific pathways to initiate sympathetic outflow and OT is
      a specific component of the sympathetic pathway innervating the spleen.

PMID- 14583237
TI  - The effects of lateral hypothalamic lesions on peripheral blood natural killer
      cell cytotoxicity in rats hyper- and hyporesponsive to novelty.
AB  - Individual variability in the central control of the cellular immune responses is
      the main subject of the study. Previously, it was found that destruction of the
      lateral hypothalamus (LH) produced long-term depression of the cytotoxicity of NK
      cells (NKCC) and their number (LGL). In the present experiment we compared
      changes in the peripheral blood NKCC, LGL number, as well as leukocyte and
      lymphocyte number, their mitogenic activity and plasma corticosterone level
      evoked by electrolytic LH lesions in rats which were categorized as either high
      (HR) and low (LR) responders according to their locomotor response to a new
      environment. It was found that: (1) before the lesion NKCC (measured by 51Cr
      release assay) was higher in the HRs than in LRs; (2) LH damage caused a drop in
      NKCC and LGL number (21st postlesion day) preceded by a transient enhancement
      (5th postlesion day) significant for HRs only. As a result of a greater decrease
      in the HRs than LRs the baseline differences between groups disappeared by 21st
      postlesion day; (3) NKCC and LGL depression was not accompanied by changes in
      lytic activity of a single NK cell (agarose assay) which indicates that NKCC
      decrease concerned the population level and was dependent on LGL redistribution
      and/or recycling rate; (4) on the 21st postlesion day there was a significant
      leuko- and lymphopenia in the lesioned groups both HRs and LRs; (5) proliferative
      lymphocyte response to PWM (colorimetric assay) and plasma corticosterone level
      were not affected either by the motility level or by the lesion. The results
      emphasize the importance of individual differences in behavioral reactivity for
      NKCC regulation and a possible involvement of LH in the mechanism which connects
      high locomotor activity with stimulation of NKCC.

PMID- 14583238
TI  - Sex differences in photoperiodic and stress-induced enhancement of immune
      function in Siberian hamsters.
AB  - Siberian hamsters breed during the long days of spring and summer when
      environmental conditions (e.g., ambient temperatures, food availability) are
      favorable for reproduction. Environmental conditions may also influence the onset
      and severity of infection and disease, and photoperiodic alterations in immune
      function may comprise part of a repertoire of seasonal adaptations to help
      survive winter. In order to test the hypothesis that animals use day length to
      anticipate seasonal stressors and adjust immune function, we measured antigen
      specific delayed-type-hypersensitivity (DTH) responses in the skin of male and
      female hamsters during long, "summer-like," or short, "winter-like" days, at
      baseline and following acute restraint stress. Sex steroid hormones were lower,
      and cortisol was higher, in males and females during short days. Baseline DTH was
      enhanced in short- compared to long-day males, and acute stress augmented this
      effect. In contrast, photoperiod alone did not influence the DTH response in
      females. As predicted, female hamsters exhibited significantly higher DTH
      responses than males during long days, but not during short days. However, this
      enhancement was observed in acutely stressed females only. Cortisol
      concentrations were significantly higher at baseline in females, and increased
      more in response to stress, compared to males in both photoperiods. These results
      suggest that photoperiod provides a useful cue by which stressors in the
      environment may be anticipated in order to adjust immune function. Furthermore,
      interactions among reproductive status and stress responses appear to mediate the
      expression of sex differences in immune responses in hamsters.

PMID- 14583239
TI  - Endocrine and cytokine responses to standardized physical stress in multiple
      sclerosis.
AB  - Since the earliest descriptions psychological and physical stress has been
      considered a controversial but potentially important factor in the onset and
      course of multiple sclerosis (MS). During recent years it has become clear that
      MS patients benefit from physical exercise as performed in aerobic training. As
      acute exercise has profound effects on immune and endocrine parameters we studied
      endocrine and immune response to standardized physical stress in MS within a
      study of aerobic training. Fifteen MS patients completed an eight-week aerobic
      training program, 13 patients were part of a wait-control group. Twenty healthy
      controls were recruited as well. A step-by-step bicycle ergometry was performed
      to determine individual exertion levels. For the endurance test patients
      exercised at 60% VO2 max for 30 min. Blood samples were drawn before, directly
      after and 30 min after completion of the exercise. Heart rate and lactate
      increased in all groups (p<.0001). We furthermore saw significant increases in
      endocrine parameters (epinephrine, norepinephrine, ACTH, and beta-endorphin; all
      p<.0001) in healthy individuals and in MS patients but without a differential
      effect. Whole-blood stimulated production of IFN-gamma (IFNgamma) was induced
      similarly in all groups (p<.01). TNF-alpha (TNFalpha) and IL-10 were less
      inducible in MS patients (trend). From these data we could not demonstrate a
      proinflammatory immune deviation in response to physical stress in MS. The
      observed trend of hyporesponsive TNFalpha and IL-10 responses in MS warrants
      further investigation.

PMID- 14583240
TI  - Contribution of the adrenal glands and splenic nerve to LPS-induced splenic
      cytokine production in the rat.
AB  - Both the hypothalamic pituitary adrenal axis (HPAA) and the sympathetic nervous
      system (SNS) can inhibit immune function and are regarded as the primary efferent
      pathways for neural-immune interactions. To determine if this relationship is
      maintained in vivo in response to an inflammatory stimulus, rats were injected
      intravenously (iv) with various doses of lipopolysaccharide (LPS) and splenic
      cytokine mRNA and protein levels were measured at several dose and time intervals
      post-injection. The spleen was chosen as the target organ because both the neural
      and hormonal inputs to the spleen can be selectively removed by splenic nerve cut
      (SNC) and adrenalectomy (ADX), respectively. Data from our dose response studies
      established that maximum levels of splenic cytokines were induced in response to
      relatively low doses of LPS. Minimal changes in LPS-induced splenic cytokine
      levels were observed in response to ADX, SNC, or a combination of the two
      procedures across several doses of LPS. These results suggest that there are
      aspects of immune regulation that are functionally removed from these central
      modulatory systems and that the counter-regulatory responses induced by LPS have
      minimal impact on the concurrent induction of cytokines by this inflammatory
      stimulus. The conceptual model of neural-immune regulation as an inhibitory
      feedback system, at least with regards to the early activational effects induced
      by an inflammatory stimulus, was not supported by these studies.

PMID- 14583241
TI  - Sleep-deprived mice show altered cytokine production manifest by perturbations in
      serum IL-1ra, TNFa, and IL-6 levels.
AB  - Serum cytokine and chemokine levels were examined in mice following 36 h of sleep
      deprivation, or after exposure to a known physical stressor (rotational stress).
      Significant changes in inflammatory cytokines/chemokines (IL-1beta, TNFalpha, IL
      1ra, IL-6, and MIP-1beta, MCP-1) were observed following each manipulation, but
      qualitative and quantitative differences were seen. Interestingly, only physical
      stress was associated with measured increases in serum corticosterone levels, and
      with independent evidence (using in vitro immune allostimulation) for a
      generalized immunosuppression secondary to the experimental manipulation. Our
      data suggest that altered cytokine production following sleep perturbation occurs
      by a different mechanism from that (HPA axis) commonly attributed to stress per
      se.

PMID- 14583242
TI  - Environmental performance review and cost analysis of MSW landfilling by baling
      wrapping technology versus conventional system.
AB  - This paper first reviews the chemical, physical and biological processes, and the
      environmental performance of MSW compacted and plastic-wrapped into air-tight
      bales with low-density polyethylene (LDPE). The baling-wrapping process halts the
      short and half-term biological activity and consequently the emission of gases
      and leachates. It also facilitates the handling of the refuse, and considerably
      reduces the main environmental impacts of a landfill. The main technologies
      available for baling-wrapping MSW are also presented. Furthermore, a cost
      analysis comparing a conventional landfill (CL) without baling system versus two
      landfills using different baling-wrapping technologies (rectangular and
      cylindrical bales) is carried out. The results are presented comparatively under
      the conditions of construction, operation and maintenance and postclosure, as
      required by European Directive 1999/31. A landfill using rectangular plastic
      wrapped bales (LRPB) represents an economically competitive option compared to a
      CL. The increased capacity of the waste disposal zone when using rectangular
      bales due to the high density of the bales compensates for the increased
      operating and maintenance (O&M) costs of the method. Landfills using cylindrical
      plastic-wrapped bales (LCPB's) do not fare so well, mainly because the density
      within the bales is lower, the cylindrical geometry of the bales does not allow
      such an efficient use of the space within the landfill, and the processing
      capacity of the machinery is lower. From the cost model, the resulting unit costs
      per tonne in a LRPB, a LCPB and a CL for 100,000 t/year of waste, an operation
      time of 15 years and a landfill depth (H) of 20 m, are 31.52, 43.36 and 31.83 /t,
      respectively.

PMID- 14583243
TI  - Solid waste management in Indian Himalayan tourists' treks: a case study in and
      around the Valley of Flowers and Hemkund Sahib.
AB  - Solid waste generation in sensitive tourist areas of the Indian Himalayan region
      is approaching that of some metro cities of the country. The present study showed
      approximately 288 g waste generation visitor(-1) day(-1) compared with the nation
      wide average of 350 g capita(-1) day(-1). About 29 metric tonnes (MT) solid waste
      is generated along a distance of about 19-km trek (a stretch of land or distance
      between two or more places covered by a walk) during a 4-month tourist season
      every year. Treks and trek stalls are the two major places where the visitors
      generate solid waste. Waste estimated from stalls accounted for about 51% by
      weight of the total waste generation in the trekking region. The native villagers
      generally construct stalls every year to meet the requirement of visitors going
      to Valley of Flowers (VOF) and Hemkund Sahib. The average annual results of 2
      years (or equivalent to the average of one, 4-month tourist season for the
      region) showed non-biodegradable waste (NBW) to be 96.3% by weight whereas
      biodegradable waste (BW) amounted to merely 3.7%. From management point of view
      of the government, 96% NBW could easily be reused and recycled. Nevertheless, the
      need is to manage this waste by bringing it from the trekking areas to the road
      head (Govind Ghat) first and then to transport it to adjacent recycling centers.
      Cold drink glass bottles (68%), plastic (26%) and metal (2%) were the major items
      contributing to non-biodegradable waste. The remaining organic waste could be
      used as feedstock for composting. A well coordinated effort of public
      participation is necessary at all the levels for managing waste. There is a need
      to educate the visitors to instill in them the habit of considering discarded
      waste as potentially valuable and manageable.

PMID- 14583244
TI  - Assessment and analysis of industrial liquid waste and sludge disposal at unlined
      landfill sites in arid climate.
AB  - Municipal solid waste disposal sites in arid countries such as Kuwait receive
      various types of waste materials like sewage sludge, chemical waste and other
      debris. Large amounts of leachate are expected to be generated due to the
      improper disposal of industrial wastewater, sewage sludge and chemical wastes
      with municipal solid waste at landfill sites even though the rainwater is scarce.
      Almost 95% of all solid waste generated in Kuwait during the last 10 years was
      dumped in five unlined landfills. The sites accepting liquid waste consist of old
      sand quarries that do not follow any specific engineering guidelines. With the
      current practice, contamination of the ground water table is possible due to the
      close location of the water table beneath the bottom of the waste disposal sites.
      This study determined the percentage of industrial liquid waste and sludge of the
      total waste dumped at the landfill sites, analyzed the chemical characteristics
      of liquid waste stream and contaminated water at disposal sites, and finally
      evaluated the possible risk posed by the continuous dumping of such wastes at the
      unlined landfills. Statistical analysis has been performed on the disposal and
      characterization of industrial wastewater and sludge at five active landfill
      sites. The chemical analysis shows that all the industrial wastes and sludge have
      high concentrations of COD, suspended solids, and heavy metals. Results show that
      from 1993 to 2000, 5.14+/-1.13 million t of total wastes were disposed per year
      in all active landfill sites in Kuwait. The share of industrial liquid and sludge
      waste was 1.85+/-0.19 million t representing 37.22+/-6.85% of total waste
      disposed in all landfill sites. Such wastes contribute to landfill leachate which
      pollutes groundwater and may enter the food chain causing adverse health effects.
      Lined evaporation ponds are suggested as an economical and safe solution for
      industrial wastewater and sludge disposal in the arid climate of Kuwait.

PMID- 14583245
TI  - Chemical-mechanical characteristics of crushed oyster-shell.
AB  - Enormous amount of oyster-shell waste has been illegally disposed at oyster farm
      sites along the southern coast of Korea. To seek for a possibility to recycle the
      waste as construction materials, chemical and mechanical characteristics of
      crushed oyster-shell were investigated. Chemical and microstructure analyses
      showed that oyster-shells are predominantly composed of calcium carbonate with
      rare impurities. Compressive strength tests for soil mortar specimens with
      varying blending ratio of cement, water, sand, and oyster-shell were compared
      with normal cement mortar. There was no significant reduction in the compressive
      strength up to 40% of dosages of oyster-shell instead of sand. The experimental
      results demonstrate that oyster-shells can be resources of pure calcareous
      materials and effective in replacement of sand, indicating promising reusable
      construction materials.

PMID- 14583246
TI  - Towards zero discharge of chromium-containing leather waste through improved
      alkali hydrolysis.
AB  - The treatment of chromium-containing leather waste (CCLW), the major solid waste
      generated at the post-tanning operations of leather processing, has the potential
      to generate value-added leather chemicals. Various alkali and enzymatic
      hydrolysis were compared, and calcium oxide was found to be important for
      effective (but still incomplete) hydrolysis. Three possible reasons are given for
      the incomplete hydrolysis under alkaline conditions. Data for 19 amino acids are
      presented for four different treatment products. On the basis of the results, a
      novel three-step CCLW treatment process is proposed. The gelatin extracted in the
      first step is chemically modified to produce leather finishing agents. The
      collagen hydrolysates isolated in the second step are used as proteinic retanning
      agents by chemical modification. The remaining chrome cake is further hydrolyzed
      with acids in the third step, and the obtained chromium-containing protein
      hydrolysates could be used for the preparation of chromium-containing retanning
      agents for leather industry. The proposed three-step process provides a feasible
      zero discharge process for the treatment of CCLW.

PMID- 14583248
TI  - The adsorption characteristics of heavy metals by various particle sizes of MSWI
      bottom ash.
AB  - The incineration rate of municipal solid waste (MSW) has been increased because
      of difficulty in securing a proper disposal site for MSW in Korea. The advantage
      of incineration is reduction of the volume of waste; however, significant amounts
      of bottom ash and fly ash were generated in the incineration process. Their
      treatment has attracted growing interest because of the potential toxicity of
      hazardous heavy metals. Generally, heavy metals are less released from bottom ash
      than from fly ash. In this study the adsorption characteristics of heavy metals
      were investigated using various particle sizes of MSWI bottom ash. Since bottom
      ash has a broad particle size distribution, it was sieved to size classes of +20,
      -20, -48, -80, -100 mesh. Cation exchange capacity (CEC) was analyzed by the
      ammonium acetate method to evaluate the potential as an adsorbent. The CEC values
      and surface areas increase as the range of particle size becomes finer. The
      adsorption experiment was conducted using synthetic (Cu and Ni) and plating rinse
      water as a function of reaction time (10-180 min), liquid/solid ratio (2-100) and
      particle size (+20 to -100 mesh), respectively. The adsorption rate increased
      with decreasing particle size and with increasing liquid/solid ratio; however,
      the removal efficiency of Cu was higher than that of Ni. In the case of plating
      rinse water, the adsorption rate decreased sharply at high liquid/solid ratio,
      and it showed over 80% of adsorption rates for Cu and Ni at an initial pH of 3.

PMID- 14583247
TI  - Flame treatment for the selective wetting and separation of PVC and PET.
AB  - Flame treatment has been used for many years to modify the surface of plastics to
      allow coatings to be added. The effect of the treatment is to produce hydrophilic
      species on the surface of the plastic making it water-wettable. The production of
      hydrophilic plastic surfaces is also required in the selective separation of
      plastics by froth flotation. For the process to be selective one plastic must be
      rendered hydrophilic while another remains hydrophobic. In this study the
      potential for separation of PVC and PET has been investigated. Flame treatment
      was shown to be very effective in producing a hydrophilic surface on both
      plastics, although the process was not selective under the conditions
      investigated. Raising the temperature of the plastics above their softening point
      produced a hydrophobic recovery. As the softening point of PVC was significantly
      lower than for PET it was possible to produce a significant difference in
      hydrophobicity, as judged using contact angle measurement. When immersed in water
      the contact angle of the PVC was found to be strongly dependent on the pH. Good
      separation efficiency of the two plastics was achieved by froth flotation from pH
      4 to 9. One particular advantage of the technique is that no chemical reagents
      may be required in the flotation stage. The practicalities of designing a flake
      treatment system however have to be addressed before considering it to be a
      viable industrial process.

PMID- 14583249
TI  - The behaviour of ashes and heavy metals during the co-combustion of sewage
      sludges in a fluidised bed.
AB  - Co-combustion tests of dry sewage sludges with coal were performed in a pilot
      bubbling FBC aiming at the characterization of ashes and determining the
      behaviour of heavy metals in the process. The tests showed compliance with the
      regulatory levels as far as heavy metal emissions were concerned. The bottom
      ashes, which accounted for about 70% of the total ash production, were obtained
      in a granular form, with diameters ranging from 0.5 to 4 mm. The heavy metals
      were distributed in ashes obtained from different locations of the installation
      and their concentrations were found to vary depending on the location of capture.
      The increase in heavy metals content in bottom ashes was not found to lead to
      higher leachability and ecotoxicity compared to sewage sludges, suggesting that
      there could be opportunities for their further use. Mercury suffered vaporisation
      inside the reactor, thus leaving bottom ashes free of contamination by it.
      However, there was observed a strong retention of mercury in cyclone ashes due to
      the presence of unburned carbon which probably acted as an adsorbent. The
      effluent mercury was also found to be mostly associated with the particulate
      fraction, being less than 20% emitted in gaseous forms. The results suggested
      that the combustion of the sewage sludge could successfully be carried out and
      the amount of unburned carbon leaving the combustor but captured in cyclone was
      large enough to ensure substantial retention of mercury at low temperatures,
      hence could contribute to an improvement of the mercury release which still
      remains an issue of great concern to resolve during combustion of waste
      materials.

PMID- 14583250
TI  - Nickel immobilization in ceramic matrix admixed with waste nickel hydroxide.
AB  - WAXS examinations performed with nickel hydroxide samples heated to various
      temperatures showed that freshly settled wet nickel hydroxide sample contains
      some amount of crystalline beta-Ni(OH)(2) structure and its share increased when
      sample was dried during 3 weeks at ambient temperature. However, the share
      significantly decreased when the sample was dried at 110 degrees C and more so at
      250 degrees C. Crystalline phase traces of Ni(OH)(2) disappeared after sample
      burning at 980 degrees C and instead the distinct presence of crystalline NiO was
      determined. The above samples were examined for solubility in stoichiometric
      amount of sulphuric acid diluted with water to pH 1.9 and 2.8. Solubility was
      determined by measuring nickel ion concentration in leachate by the AAS method.
      The dissolving rate was found to decrease with the rise of temperature to which
      the nickel hydroxide samples were heated. The solubility of Ni(OH)(2) sample
      burnt at 980 degrees C was undetectable during 90 h solubility-testing time
      likely due to its transformation into sparingly soluble crystalline NiO. The
      latter is considered to be the reason for effective immobilization of waste
      nickel hydroxide in ceramic prepared by blending with clay and sintering at 980
      degrees C.

PMID- 14583251
TI  - Horizontal standardisation of test methods for waste, secondary raw materials,
      construction materials, sludge, biowaste and (contaminated) soil.

PMID- 14583252
TI  - Metabolix, Inc. and Tepha, Inc. Bioplastics for industry and medical devices.

PMID- 14583253
TI  - Site-selective DNA binding drugs.

PMID- 14583254
TI  - Vaccine delivery by carbon nanotubes.

PMID- 14583255
TI  - New structural insights into the inhibition of serine proteases by cyclic
      peptides from bacteria.

PMID- 14583256
TI  - Zebrafish-based small molecule discovery.

PMID- 14583257
TI  - Transcription activation by a PNA-peptide chimera in a mammalian cell extract.

PMID- 14583258
TI  - Protein evolution by "codon shuffling": a novel method for generating highly
      variant mutant libraries by assembly of hexamer DNA duplexes.

PMID- 14583259
TI  - Cellular interacting proteins of functional screen-derived antiproliferative and
      cytotoxic peptides discovered using shotgun peptide sequencing.

PMID- 14583260
TI  - Melithiazol biosynthesis: further insights into myxobacterial PKS/NRPS systems
      and evidence for a new subclass of methyl transferases.

PMID- 14583261
TI  - Markerless mutations in the myxothiazol biosynthetic gene cluster: a delicate
      megasynthetase with a superfluous nonribosomal peptide synthetase domain.

PMID- 14583262
TI  - Immunization with peptide-functionalized carbon nanotubes enhances virus-specific
      neutralizing antibody responses.

PMID- 14583263
TI  - Simultaneous in vitro assay of the first four enzymes in the fungal aspartate
      pathway identifies a new class of aspartate kinase inhibitor.

PMID- 14583264
TI  - Cellular localization and antiproliferative effect of peptides discovered from a
      functional screen of a retrovirally delivered random peptide library.

PMID- 14583266
TI  - Binding structure of elastase inhibitor scyptolin A.
AB  - Natural bioactive compounds are of general interest to pharmaceutical research
      because they may be used as leads in drug development campaigns. Among them,
      scyptolin A and B from Scytonema hofmanni PCC 7110 are known to inhibit porcine
      pancreatic elastase, which in turn resembles the attractive drug target
      neutrophil elastase. The crystal structure of scyptolin A as bound to pancreatic
      elastase was solved at 2.8 A resolution. The inhibitor occupies the most
      prominent subsites S1 through S4 of the elastase and prevents a hydrolytic attack
      by covering the active center with its rigid ring structure. The observed binding
      structure may help to design potent elastase inhibitors.

PMID- 14583265
TI  - Enzyme-assisted suicide: molecular basis for the antifungal activity of 5-hydroxy
      4-oxonorvaline by potent inhibition of homoserine dehydrogenase.
AB  - The structure of the antifungal drug 5-hydroxy-4-oxonorvaline (HON) in complex
      with its target homoserine dehydrogenase (HSD) has been determined by X-ray
      diffraction to 2.6 A resolution. HON shows potent in vitro and in vivo activity
      against various fungal pathogens despite its weak (2 mM) affinity for HSD in the
      steady state. The structure together with structure-activity relationship
      studies, mass spectrometry experiments, and spectroscopic data reveals that the
      molecular mechanism of antifungal action conferred by HON involves enzyme
      dependent formation of a covalent adduct between C4 of the nicotinamide ring of
      NAD(+) and C5 of HON. Furthermore, novel interactions are involved in stabilizing
      the (HON*NAD)-adduct, which are not observed in the enzyme's ternary complex
      structure. These findings clarify the apparent paradox of the potent antifungal
      actions of HON given its weak steady-state inhibition characteristics.

PMID- 14583267
TI  - Study on structural variation of silica gel using Nd3+ as a probe by
      photoacoustic spectroscopy.
AB  - The structural variations of silica gels heated at different temperatures have
      been firstly studied using Nd(3+) as a probe by photoacoustic spectroscopy (PAS),
      together with IR spectroscopy and thermal analysis. With increasing temperature,
      the f-f transitions of Nd(3+) show a red shift and the PA intensities increase.
      The PA branching vector of the transitions from ground state to
      4G(5/2)+(2)G(7/2), which are hypersensitive transitions, increase and the others
      decrease or change little. These indicate that the covalency of the bond that
      Nd(3+) forms increases and the symmetry around Nd(3+) decreases, which reflects
      the structural variations of silica gels.

PMID- 14583268
TI  - Studies of solvation in homogeneous and heterogeneous media by electronic
      spectroscopic method.
AB  - Solvation characteristics in homogenous (pure and mixed binary solvents) and
      heterogeneous media (aqueous micelles, beta- and gamma-cyclodextrine solutions)
      have been studied by monitoring the emission characteristics of a newly
      synthesised dye. The longest wavelength absorption and emission band of the dye
      arise due to transition between S(0) and S(1) state. The maximum energy of
      electronic transition involving intramolecular charge transfer is found to be
      dependent on both the hydrogen-bond donating ability and the polarity
      polarisability in pure solvent. The dipole moment in the S(1) state, as
      determined by solvatochromic procedure, agrees well with the value obtained by
      theoretical calculation at the AM1 level. Preferential solvation of the dye by
      alcohols has been found to occur in ethanol+water, propan-1-ol+water, propan-2
      ol+water binary mixtures. In aqueous micellar media the dye molecule is located
      at the water-micelle interface. The binding constant for the dye-micelle
      interaction has also been determined. The results have been compared with those
      for a structurally related symmetrical ketocyanine dye.

PMID- 14583270
TI  - Growth and vibrational spectra of doped KMgF3 single crystal.
AB  - The different ions doped KMgF(3) single crystals are prepared by the vertical
      Bridgman method. The near-infrared absorption spectra for different parts of all
      as-growth crystals indicate that there is the best transparency in middle part.
      The correlation between the vibronic frequencies of Eu(2+) and the site
      displacement of Cu(+) co-doped ions is firstly studied, which indicates that
      Cu(+) ions replace the site of the Mg(2+) ions. The co-doped Eu(2+) counteracts
      the charge misfit causing by the replacement of Mg(2+) with Cu(+). The
      overlapping of the emission spectra of the Eu(2+) and the excitation spectra of
      the Cu(+) results in the energy transfer from Eu(2+) to Cu(+).

PMID- 14583269
TI  - Study on the interaction of methylene blue with cyclodextrin derivatives by
      absorption and fluorescence spectroscopy.
AB  - The ability of beta-cyclodextrin (beta-CD), hydroxypropyl-beta-cyclodextrin (HP
      beta-CD), and carboxymethyl-beta-cyclodextrin (CM-beta-CD) to break the aggregate
      of the methylene blue (MB) and to form 1:1 inclusion complexes has been studied
      by absorption and fluorescence spectroscopy. Experimental conditions including
      concentrations of various cyclodextrins (beta-CD, HP-beta-CD and CM-beta-CD) and
      media acidity were investigated for the inclusion formation in detail. The
      formation constants are calculated by using steady-state fluorimetry, from which
      the inclusion capacity of different cyclodextrins (CDs) is compared. The results
      suggest that the charged beta-cyclodextrin (CM-beta-CD) is more suitable for
      inclusion of the cationic dye MB than the neutral beta-cyclodextrins (beta-CD, HP
      beta-CD) at pH>5. A mechanism is proposed which is consistent with the stronger
      binding of MB with CM-beta-CD compared with the other CDs at pH>5.

PMID- 14583271
TI  - Synthesis and luminescence of zinc and europium alpha-thiophene carboxylate
      polymer.
AB  - The zinc and europium alpha-thiophene carboxylate polymer with very strong red
      luminescence was prepared by rheological phase reaction method from zinc acetate,
      europium oxide and alpha-thiophenecarboxylic acid. Molecular weight, thermal
      analyses and X-ray diffraction pattern were measured. 1H NMR, 13C NMR, IR, XPS,
      UV, excitation and emission spectra were studied. The polymer with amorphous
      structure and 7.565x10(5) g/mol weight-average molecular exhibited excellent
      solubility in common organic solvents and better thermal stability under 270
      degrees C in air. The quantum yield of the polymer in acetone was 0.6 relative to
      quinoline in 0.05 mol/l H(2)SO(4) solution. The energy of the pi,pi(*) excited
      state of C(4)H(3)SCO(2)(-) can be transferred to Eu(3+) ion resulting in emission
      from the 5D(0)-->(7)F(j) of Eu(3+) ion through the polymeric chains. Zn(2+) can
      effectively enhance the luminescence of Eu(3+) in alpha-thiophenecarboxylate
      polymer.

PMID- 14583272
TI  - Structural studies of marine exoskeletons: redox mechanisms observed in the Cu
      supported CaCO3 surfaces tudied by EPR.
AB  - Electron Paramagnetic Resonance (EPR), optical and infrared (IR) spectral studies
      have been performed on the pure and Cu-adsorbed exoskeletons of marine
      environment. The EPR spectrum of exoskeletons at room temperature exhibits a
      sharp signal at g approximately 1.9970. The possible redox mechanisms have been
      noticed on heating these exoskeletons in which the low spin Mn(3+) reduces to
      Mn(2+). The optical absorption spectra also give the evidence of the presence of
      Mn(3+) ions. The effects of thermal sintering on the EPR spectra have been
      studied and discussed in detail. The Cu-adsorbed samples clearly showed the
      adsorption of the Cu(2+) ions over CaCO(3) and the redox mechanism in these
      samples have been monitored by EPR.

PMID- 14583274
TI  - FT-Raman and photoacoustic infrared spectroscopy of syncrude light gas oil
      distillation fractions.
AB  - FT-Raman and photoacoustic (PA) infrared spectra of 12 distillation fractions
      derived from Syncrude light gas oil (LGO), which has a boiling range from 195 to
      343 degrees C, were analyzed in detail in this study. In the fingerprint region
      (200-1800 cm(-1)) most of the information is obtained from the FT-Raman spectra,
      which display 36 bands that are assignable to various alkyl or aryl functional
      groups. Monocyclic, bicyclic and tricyclic aromatics in the 12 fractions were
      also characterized using Raman bands in this region. The corresponding section of
      the infrared spectra is much simpler, displaying a relatively small number of
      bands due to either aromatic or aliphatic CH(n) (n=1, 2 or 3) groups. The
      Cz.sbnd;H stretching region in both FT-Raman and PA infrared spectra of the LGO
      distillation fractions was curve-fitted according to procedures established in
      previous investigations of Syncrude samples with various boiling ranges. The PA
      spectra of the LGO fractions were also analyzed using an accepted integration
      strategy that requires no a priori assumptions with regard to the number of
      constituent bands or their shapes. The curve-fitting results show that the
      frequencies of the 11 Raman and eight infrared bands used to model the aliphatic
      ( approximately 2775-3000 cm(-1)) parts of the respective spectra decrease
      systematically as the median boiling points of the LGO fractions increase. These
      band positions are consistent with those determined in earlier studies of other
      distillation fractions. Both curve fitting and integration show that the
      abundance of CH(2) groups increases at the expense of CH(3) groups as the boiling
      points of the fractions increase within the LGO region.

PMID- 14583273
TI  - Study on the binding mode of zinc(II) protoporphyrin and ctDNA in water.
AB  - Spectroscopic property of a commercially available luminescent reagent Zinc(II)
      protoporphyrin (ZnPP) was studied. Dissociation constants of the two protons on
      the peripheral groups of porphyrin ring of ZnPP were determined as pK(a1)=6.31,
      pK(a2)=9.37. Binding evidence of ZnPP with ctDNA was found by the phosphorescence
      intensity change on a filter paper around pH 6.5-9.3 with the association
      constant being 9.1x10(3) dm(3)/mol. A novel binding mode for ZnPP and calf thymus
      DNA (ctDNA) suggested that the monomer ZnPP which has no axial coordination,
      slips into the groove of DNA and interacts with the bases of polynucleotide by
      zinc coordination and hydrogen bonding between H atom on carboxyl group of ZnPP
      and O atom on the bases.

PMID- 14583275
TI  - UV solvatochromic shifts of 4-hydroxy-benzophenone and 2,4-dihydroxy-benzophenone
      in ethanol-acetonitrile mixtures.
AB  - The anomalous UV spectroscopic behavior of 4-hydroxy-benzophenone and 2,4
      dihydroxy-benzophenone in ethanol-acetonitrile mixtures has been investigated
      using theoretical and experimental methods. Band I of these compounds, associated
      to strong pi-->pi* transitions, suffers a blue shift when the polarity of the
      ethanol-acetonitrile solutions increases. The magnitude of the solvatochromic
      shifts suffered by the analyzed benzophenones (BPs) changes inversely with the
      planarity of their molecules. The experimental solvatochromic shifts of the
      compounds were correlated with the permittivity and the solvation parameters
      alpha and pi* that characterize the ethanol-acetonitrile mixtures used. In order
      to explain theoretically the observed solvatochromic shifts, it was proposed that
      in solution, the two compounds form an association complex of stoichiometry 1:1
      with a molecule of ethanol. These complexes are formed by means of an
      intermolecular hydrogen bond between the hydrogen atom of 4-OH group of the
      solutes and the oxygen atom of ethanol. The calculations performed at the HRF/6
      31G(d) level of theory using Onsager's and Tomasi's models showed that these
      solute-ethanol association complexes have an elevated thermodynamic stability.
      Good linear relations were obtained between the experimental absorption
      frequencies of BPs and the theoretical absorption frequencies of the association
      complexes. These frequencies were also very satisfactorily correlated with the
      properties of the above mentioned ethanol-acetonitrile mixtures. It was concluded
      that the magnitude of the analyzed solvatochromic shifts is determined by the
      degree of occurrence of solute-solvent interactions, which essentially depend on
      the polarity, polarizability and hydrogen bond donating ability of the ethanol
      acetonitrile mixtures.

PMID- 14583276
TI  - In situ investigation of laser-induced ignition and the early stages of methane
      air combustion at high pressures using a rapidly tuned diode laser at 2.55
      microm.
AB  - The laser-induced ignition of methane/air-mixtures at elevated pressures was
      investigated by an absorption spectroscopic technique. A room temperature
      continuous wave InGaAsSb/AlGaAsSb quantum well ridge diode laser was wavelength
      tuned around 2.55 mum by periodically modulating the injection current from 0 to
      174 mA at a 5 kHz repetition rate. The laser heat sink temperature was fixed at
      291 K. The infrared laser beam was sent through the pressurized combustion vessel
      perpendicularly to the igniting laser beam (Nd:YAG laser, 10 ns pulse duration,
      20 mJ) at the position of the ignition spark. Fuel-rich to fuel-lean mixtures of
      methane/air (air equivalence ratio 0.89, 1.06, 1.42, 2.50) were investigated at
      initial pressures of up to 3 MPa. The initial temperature was 473 K, the volume
      of the combustion vessel 0.9x10(-3) m(3). The formation of water vapor in the
      vicinity of the laser spark was tracked by the diode laser. The time resolution
      of the measurements was 0.2 ms for a total continuous measurement time of up to 1
      s. In this way, the laser-induced ignition and its accompanying effects could be
      investigated on a time scale spanning four orders of magnitude. Apart from the
      absorbance of water vapor which could be determined semi-quantitatively (due to
      the effects of severe pressure broadening at high pressures and the ignorance of
      the exact temperature distribution after ignition), the emissions from the flame
      (broadband, 1-10 mum) and a gas inhomogeneity index were recorded. The gas
      inhomogeneity index was obtained by extracting a frequency variable from the time
      dependent fluctuations of the transmitted laser intensities and calculating its
      derivation. The absorbance of water vapor, the emissions from the flame and the
      gas inhomogeneity index were found to be a powerful tool to characterize laser
      induced ignition. Major implications of in situ species concentration
      measurements at high pressures for the design and development of high-load
      combustors are presented.

PMID- 14583277
TI  - Photophysical processes in quinoxaline vapor at low pressure.
AB  - Excitation and pressure dependence of fluorescence and phosphorescence quantum
      yields has been reinvestigated in detail for quinoxaline in the static vapor
      phase at pressure range from 10(-3) to 10(-1) Torr. It is shown that the ratio of
      the nonradiative rate from T(1)(pi, pi*) to the rate of the S(1)(n, pi*)
      approximately -->T(1)(pi, pi*) intersystem crossing decreases with increasing the
      excitation energy in the S(0)-->S(1) excitation region. The phosphorescence
      quantum yield measured as a function of the excitation energy at low pressure
      shows an abrupt decrease on going the excitation from S(0)-->S(1) to S(0)-->S(2),
      indicating the slow vibrational energy redistribution between the S(1) levels
      optically populated and those populated through the internal conversion from S(2)
      to S(1).

PMID- 14583278
TI  - Carbanion substituent effects on 1-disubstituted 4-(4'-pyridyl)pyridinium
      methylide structures using 13C NMR spectroscopy and DFT method.
AB  - The structure of 1-disubstituted 4-(4'-pyridyl)pyridinium methylides or 4,4'
      bipyridinium monoylides (2-5) with a wide range of carbanion substituents, were
      determined using 13C NMR signals in dimethylsufoxide (DMSO-d(6)) solution. For
      the first time, we developed a systematic determination of 13C NMR chemical
      shifts of the ylidic carbon using a long-range correlated (1H-(13)C) HMBC
      experiments. The chemical shift values are discussed in terms of magnetic and/or
      electronic effects of the ylidic carbon substituents. From the extracted NMR
      parameters and the results of accompanying quantum chemical DFT calculations for
      a three-dimensional (3D)-structure representation, we found a long distance
      electronic effect where the aromatic heterocycle C2z.sbnd;C6 and C4 centers are
      perturbed according to the electron acceptor strengths of ylidic carbon
      substituents in all monoylides (2-5c) capable to stabilize in a planar
      conformation. No significant perturbation on C2z.sbnd;C6 and C4 centers are found
      in all other monoylides (2-5a, b) that adopted a non-planar conformation. Good
      similar linear dependences of the chemical shift variation Delta (calculated by
      the differences of analogous C2z.sbnd;C6 and C4 chemical shifts in non-planar and
      planar monoylides) with the ylidic carbon chemical shifts modulated by the
      strength of electron acceptor substituents pointed out the resonance interaction
      or the delocalization phenomena of the ylidic carbon charge on the heterocycle.

PMID- 14583279
TI  - The conversion of phenylpropanedinitrile (phenylmalononitrile) into the
      carbanion, followed by IR spectra, ab initio and DFT force field calculations.
AB  - The spectral and structural changes, caused by the conversion of
      phenylpropanedinitrile (phenylmalononitrile) into the carbanion, have been
      followed by IR spectra, ab initio HF, MP2 and DFT BLYP force field calculations.
      In agreement between theory and experiment, the conversion is accompanied with
      strong frequency decreases (with 114 cm(-1), mean value) of the cyano stretching
      bands nu(C triple bond N), dramatic increases in the corresponding integrated
      intensities (136-fold, total value), strong enhancement of the nu(C triple bond
      N) vibrational coupling and other essential spectral changes. According to the
      calculations, the strongest structural changes take place at the carbanionic
      center: (i) shortenings of the Cz-Ph and Cz-CN bonds with 0.064-0.092 A, and
      increases in the corresponding bond orders with 0.14-0.21 U; (ii) simultaneous
      enlargements of the bond angles at the same carbon atom with 7.6 degrees -9.7
      degrees, as from tetrahedral its configuration becomes trigonal. The carbanionic
      charge is distributed between the two cyano groups (0.44-0.52 e(-)), phenyl ring
      (0.31-0.34 e(-)) and carbanionic center (0.14-0.25 e(-)). The formation of
      moderately strong (CH(3))(2)S=O...H-C(CN)(2)C(6)H(5) hydrogen bonds has been
      found experimentally.

PMID- 14583280
TI  - Internal rotation in 1,2-di-(p-XC6H4)ethanes (X=H, Br, NO2): infrared spectra and
      compensation effect.
AB  - Infrared absorption spectra and internal rotation of 1,2-di-(p-XC(6)H(4))ethanes
      (X=H, Br, NO(2)) in crystalline phase, liquid and solutions at various
      temperatures have been investigated. Band fitting was applied to conformationally
      sensitive regions of the spectra, and assignment of the peaks to trans and gauche
      conformations was performed. Enthalpy and entropy differences of the conformers
      (deltaH(0) and deltaS(0)) were found to be solvent-dependent, and it is
      interpreted in terms of previously discovered compensation effect. The values
      deltaH(0) and deltaS(0) for 1,2-di-(p-NO(2)C(6)H(4))ethane obtained are unusually
      large.

PMID- 14583281
TI  - Application of InAsSb/InAsSbP and lead chalcogenide infrared diode lasers for
      photoacoustic detection in the 3.2 and 5 microm region.
AB  - An investigation of photoacoustic detection using 3.2-3.6 and 5 mum diode lasers
      is described. An inexpensive resonant photoacoustic system was developed based,
      on a simple glass cell and condenser and electret microphone (Bruel & Kjaer type
      4144/Sennheiser type K6P). The system was tested on the single rotation-vibration
      lines of C(2)H(2), CO, COS, and NH(3) gases. The best detection limits obtained
      are 300 ppm V for C(2)H(2) and 20 ppm V for COS. Potential applications of
      infrared diode laser photoacoustic detection lie in the areas of analytical
      chemistry, atmospheric research, and investigation of the kinetics of reactive
      species.

PMID- 14583282
TI  - Aluminum ions accelerated the oxidative stress of copper-mediated melanin
      formation.
AB  - A comparison between the effects of aluminum and cupric ions on the dopachrome
      (DC) conversion and the cooperation effect of the both ions in the DOPA oxidation
      to melanin pathway has been studied by UV-Vis spectrophotometric method. Both
      aluminum and cupric ions catalyze the DC conversion reaction, which is an
      important step in the melanin synthesis pathway. However, cupric ions catalyze
      the conversion of DC to yield 5,6-dihydroxyindole-2-carboxylic acid (DHICA) but
      the product of DC conversion catalyzed by aluminum is 5,6-dihydroxyindole (DHI).
      DOPA oxidation catalyzed by aluminum and cupric ions is studied in the presence
      of hydrogen peroxide. The results from our experiments provide evidence that
      aluminum can markedly increase the oxidative stress of copper-mediated the
      melanin formation and influence the properties of the melanin by means of
      changing the ratio of DHICA/DHI in the acidic environment (pH 5.5).

PMID- 14583283
TI  - Synthesis and infrared and fluorescence spectral properties of luminescent
      terbium and europium complexes with open-chain carboxylate crown ethers.
AB  - Two open-chain carboxylate crown ether ligands and their terbium(III) and
      europium(III) complexes were synthesized and characterized. The terbium and
      europium ions were found to coordinate to the carboxylate oxygens. The
      fluorescence properties of europium complexes in the solid state and terbium
      complexes in the solid state and in the organic solvent were studied in detail,
      respectively. Under the excitation of ultraviolet light, strong green
      fluorescence of solid terbium complexes and red fluorescence of solid europium
      complexes were observed. These observations show that the two ligands favor
      energy transfer to the emitting energy level of Tb(3+). Some factors that
      influencing the fluorescent intensity were also discussed.

PMID- 14583284
TI  - Vibrational frequencies and structure determination of silylgermane.
AB  - The normal mode frequencies and corresponding vibrational assignments of
      silylgermane are examined theoretically using the GAUSSIAN 98 set of quantum
      chemistry codes. All normal modes were successfully assigned to one of seven
      types of motion predicted by a group theoretical analysis (Si-H stretch, Ge-H
      stretch, Si-Ge stretch, H-Si-H bend, H-Ge-H bend, SiH(3) wag/GeH(3) wag and Si-Ge
      torsion) utilizing the C(3v) symmetry of the molecule. Predicted infrared and
      Raman intensities are presented. Molecular orbitals are presented and bonding is
      examined in terms of the molecular orbitals.

PMID- 14583285
TI  - Spectrophotometric determination of procaine hydrochloride in pharmaceutical
      products using 1,2-naphthoquinone-4-sulfonic acid as the chromogenic reagent.
AB  - Spectrophotometric determination of procaine hydrochloride is described. The
      procaine hydrochloride reacts with 1,2-naphthoquinone-4-sulfonic acid in pH 3.60
      buffer solution to form a salmon pink compound, and its maximum absorption
      wavelength is at 484 nm, epsilon(484)=5.22 x 10(3).The absorbance for procaine
      hydrochloride from 0.30 to 100 microg ml(-1) obeys Beer's law. The linear
      regression equation of the calibration graph is C=19.23A-0.03, with a linear
      regression correlative coefficient is 0.9996, the detection limit is 0.28 microg
      ml(-1); recovery is from 98.0 to 105.2%. Effects of pH, surfactant, organic
      solvent, foreign ions, and standing time on the determination of procaine
      hydrochloride have been examined. This method is rapid and simple, and can be
      used for the determination of procaine hydrochloride in injection solution of
      procaine hydrochloride. The results obtained by this method agreed with those by
      the official method (dead-stop titration).

PMID- 14583286
TI  - E.s.r., magnetic, optical and biological (SOD and antimicrobial) studies of
      imidazolate bridged Cu(II)-Zn(II) and Cu(II)-Ni(II) complexes with tris(2-amino
      ethyl)amine as capping ligand: a plausible model for superoxide dismutase.
AB  - X-band e.s.r. and optical absorption spectra of the imidazolate bridged
      heterobimetallic complexes [(tren)Cu-E-Im-Zn-(tren)](ClO(4))(3) and [(tren)Cu-E
      Im-Ni-(tren)](ClO(4))(3), where trentris(2-aminoethyl)amine, E-Im=2
      ethylimidazolate ion and the related mononuclear complexes [Cu(tren)](ClO(4))(2)
      and [(tren)Cu-E-ImH)](ClO(4))(2) have been described. Biological activities
      (superoxide dismutase and antimicrobial) have also been measured and compared
      with reported complexes.

PMID- 14583287
TI  - Temperature induced hyperchromism exhibited by Hoechst 33258: evidence of drug
      aggregation from UV-melting method.
AB  - UV-thermal denaturation is a simple optical method widely employed for
      determination of DNA stability and interaction with ligands. Thermal denaturation
      of DNA and DNA-ligand complex is usually monitored at 260 nm. These data are
      generally presented as a function of the absorption increase of DNA alone with no
      consideration of the temperature dependent hyperchromism of the free ligand.
      Since not every ligand has absorption at 260 nm, usually this property of the
      ligand is ignored. Here, we report the temperature dependent hyperchromicity
      exhibited by Hoechst 33258 in the presence and absence of DNA. The presence of
      Hoechst, added to the duplex (monophasic profile, T(m)=75 degrees C) in various
      ratios generates a new transition at lower temperature displaying biphasic
      thermal transition profiles. We attributed this new transition (hyperchromic), a
      mere contribution from Hoechst, which might exist in aggregated forms. The extent
      of drug aggregation/self-association is concentration dependent. We suggest that
      prior to UV-melting studies the thermal dependence of the free ligand should be
      investigated.

PMID- 14583288
TI  - Spectroscopy behavior of 6-Mercaptopurine, Azathiopurine, and 8-Azaguanine.
AB  - A comparative study, luminescence behavior of 6-Mercaptopurine (6-MP),
      Azathiopurine (BAN), and 8-Azaguanine (8-Azan) have been investigated including
      the low temperature phosphorescence, the low temperature fluorescence, the room
      temperature phosphorescence (RTP) and the room temperature fluorescence (RTF).
      The effect of pH on the luminescence intensity is discussed. Analytical
      characteristics of RTF and RTP of 6-MP, BAN, and 8-Azan have been studied. The
      lifetime of phosphorescence and the polarity of RTF and RTP have been examined.

PMID- 14583289
TI  - Multinuclear magnetic resonance and theoretical calculations in the study of
      structure and tautomerism of some 2-amino-N'-(aryl)-benzamidines.
AB  - 1H, 13C and 15N NMR spectra of eight 2-amino-N'-(aryl)-benzamidines and of the
      parent compound were recorded, and unequivocal chemical shift assignments through
      the use of COSY, 1H-J resolved, HETCOR and COLOC sequences were performed. 1H and
      13C chemical shifts for the nuclei of the benzamidine aromatic ring were not
      affected by the substituents present at N'-phenyl group, while the substituent
      effects in the chemical shifts of the same nuclei of N'-phenyl ring were very
      similar to the ones reported for the corresponding monosubstituted benzenes,
      indicating that there is no interaction between the two aromatic rings. 15N NMR
      spectra (DEPT sequence) show just two hydrogenated nitrogen atoms, which confirm
      that the amino form is the most stable tautomer, but the observation of a sharp
      signal and two broad signals (15N decoupled spectra), and the corresponding broad
      signal for the =C-NH(2) protons (in the 1H spectra), indicates the occurrence of
      tautomerism between the amino and imino forms, observable for some of the studied
      benzamidines. Theoretical calculations lead to the conclusion that these
      compounds occur mostly as the amino tautomer with Z configuration, which is
      stabilized by hydrogen bonding.

PMID- 14583290
TI  - Spectrophotometric and thermodynamic studies of [60]fullerene/methylbenzene
      charge transfer complexes.
AB  - The absorption spectra of charge-transfer (CT) complexes of [60]fullerene with
      liquid methylbenzenes, viz. toluene, o-xylene, m-xylene, p-xylene and mesitylene
      have been investigated in CCl(4) medium. An absorption band due to CT transition
      is observed in each case in the visible region. The experimental CT transition
      energies are well correlated (through Mulliken's equation) with the ionisation
      potentials (I(D)) of the series of methylbenzenes studied. From an analysis of
      this variation the electron affinity of [60]fullerene has been found to be 2.32
      eV. The degrees of charge transfer in the ground state of the complexes have been
      found to be very low (0.66-0.775%). It has been found that these methylbenzenes
      form stable 1:1 complexes with [60]fullerene. Formation constants of the
      complexes have been determined at four different temperatures from which the
      enthalpies and entropies of formation of the complexes have been obtained. The
      experimentally determined formation constants of the complexes of [60]fullerene
      with methylbenzenes exhibit a very good linear free energy relationship (Chem.
      Rev. 53 (1953) 191).

PMID- 14583291
TI  - Spectrophotometric reaction rate method for determination of barbituric acid by
      inhibition of the hydrochloric acid-bromate reaction.
AB  - A new kinetic-spectrophotometric method was developed for the determination of
      barbituric acid. The method is based on its inhibition effect on the reaction
      between hydrochloric acid and bromate. The decolorization of methyl orange by the
      reaction products was used to monitor the reaction spectrophotometrically at 510
      nm. The variable affecting the rate of the reaction was investigated. The method
      is simple, rapid, relatively sensitive and precise. The limit of detection is
      7.9x10(-7) M and calibration rang is 1x10(-6)-6.0x10(-4) M barbituric acid. The
      linearity range of the calibration graph is depends on bromate concentration. The
      relative standard deviation of seven replication determination of 5.6x10(-6) M
      barbituric acid was 1.8%. The influence of potential interfering substance was
      studied.

PMID- 14583293
TI  - Spectroscopic study of antileishmanial drug incubated in the promastigotes of
      Leishmania mexicana.
AB  - In this work we present spectroscopic study of Boldine (aporphine alkaloid) that
      possesses important biological activities, in particular, in interaction with the
      promastigotes of Leishmania mexicana. The results show the applicability of
      autofluorescence of this drug to determinate the possible mechanism of its
      biological action. The blue shift and hyperchromic effect in the emission
      spectrum of the drug in interaction with the parasite cells indicate an energy
      transference process between them. The morphological change of cell shape of the
      promastigotes treated with the drug is observed using confocal microscopy. This
      morphological cell-shape transformation evidences an important interaction
      between the drug studied and some protein of the parasite cell. Here we describe
      for the first time the fluorescence properties of the Boldine in the
      promastigotes of L. mexicana.

PMID- 14583292
TI  - Fluorescence assay for monitoring Zn-deficient superoxide dismutase in vitro.
AB  - A method has been developed for selective detection of the zinc-deficient form of
      Cu, Zn superoxide dismutase (SOD1) in vitro. Zinc-deficient SOD1 mutants have
      been implicated in the death of motor neurons leading in amyotrophic lateral
      sclerosis (ALS or Lou Gerhig's disease). Thus, this method may have applicability
      for detecting zinc-deficient SOD1 mutants in human ALS patients samples as well
      as in a transgenic mouse model of ALS and in cultured motor neurons. We
      determined previously that structural analogs of 1,10 phenanthroline, which react
      specifically with Cu(I), react with the active Cu(I) of SOD1 when zinc is absent,
      but not when zinc is also bound, as evidenced by the fact that the reaction is
      inhibited by pretreatment of the enzyme with zinc. We report herein that
      bathocuproine, or its water-soluble derivative bathocuproine disulfonate, react
      with zinc-deficient SOD1 to form a complex which fluoresces at 734 nm when
      excited at 482 nm. Fluorescent intensity is concentration dependent, thus we
      propose to use fluorescent confocal microscopy to measure intracellular levels of
      zinc-deficient SOD1 in situ.

PMID- 14583294
TI  - Study on Escherichia coli alkaline phosphatase conformation by phosphorimetry in
      the presence of denaturant.
AB  - The influence of different denaturants on the phosphorescence spectrum and
      lifetime decay of Escherichia coli alkaline phosphatase (AP) was investigated.
      Phosphorescence intensity and lifetime of tryptophan residue (Trp-109) decrease
      upon addition of guanidine hydrochloride, ethylene diamine tetraacetic acid, and
      urea or decreasing acidity. The experiments show that AP undergoes different
      pathways with different denaturants and that the activation energy data, DeltaS
      degrees (not equal) and deltaH degrees (not equal) further confirm that there is
      a stable intermediate state between the folded and unfolded AP states in
      solution.

PMID- 14583295
TI  - Spectrophotometric study on the stability of dopamine and the determination of
      its acidity constants.
AB  - The interest in determining the acidity constants of the catecholamines stems
      from the fact that they play rather an important biological role. The present
      work reveals the effect of different parameters such as oxygen, light, analysis
      time and pH on the dopamine oxidation process, where oxygen has an effect on the
      dopamine oxidation of 40% and up to 20% is attributed to exposure to light as a
      function of the pH. The application of adequate control on the said parameters
      (which ensured stability of the dopamine) facilitated the determination of the
      corresponding three acidity constants, 9.046+/-0.147, 10.579+/-0.148 and 12.071+/
      0.069.

PMID- 14583296
TI  - Adsorption of 2-chloropyridine on oxides--an infrared spectroscopic study.
AB  - The adsorption of 2-chloropyridine on SiO(2), TiO(2), ZrO(2), SiO(2)-Al(2)O(3)
      and H-mordenite has been studied by IR spectroscopy. The different modes of
      interaction with oxide surfaces, i.e. hydrogen-bonding and adsorption at Bronsted
      or Lewis acid sites, was modelled by ab initio calculations at the B3LYP/DZ+(d)
      level. Adsorption on SiO(2) results in hydrogen bonding to surface hydroxyl
      groups, whereas the spectra obtained following adsorption on TiO(2) and ZrO(2)
      display evidence for electron transfer at Lewis acidic surface sites. Protonation
      of 2-chloropyridine at Bronsted acidic sites was detected only for adsorption on
      SiO(2)-Al(2)O(3) and H-mordenite, indicating the presence of Bronsted acidic
      sites on these oxide surfaces with pK(a) values </=0.70. IR studies of 2
      chloropyridine adsorption can provide useful information regarding the nature of
      surface acidity on oxides which is complementary to that obtained from other
      probe molecules such as NHs and pyridine.

PMID- 14583297
TI  - Impact of minimally invasive trans-cervical thymectomy on outcome in patients
      with myasthenia gravis.
AB  - OBJECTIVE: To study the impact of minimally invasive trans-cervical thymectomy on
      the incidence of remission of patients with myasthenia gravis (MG) in a single
      institution over a 10-year period. METHODS: A total of 120 consecutive patients
      referred for video-assisted trans-cervical thymectomy between 1991 and 2000 were
      included in the analysis. Complete remission was defined as no symptoms and no
      treatment for 6 months, and remission as minimal ocular symptoms (slight ptosis)
      or treatment with pyridostigmine only for 6 months. RESULTS: There were 86
      females and 34 males with a median age of 33 (range 14-79) and 36 years (range 12
      68), respectively. Symptoms of MG lasted between 2 months and 17 years before
      thymectomy (median 10 months). Surgery was converted to a partial upper
      sternotomy in 23 cases (19%). The median hospital stay decreased from 2 days
      (range 1-8) before 1994 to 1 day (range 1-8) thereafter (p<0.0001). Postoperative
      complications occurred in four patients (3.3%). After a median follow-up of 48
      months (range 6-117 months), 50% of the patients were in complete remission (41%)
      or in remission (9%). Kaplan-Meier estimates rate of complete remission were 30%
      after 5 years of follow-up and 91% after 10 years. CONCLUSIONS: Minimally
      invasive trans-cervical thymectomy can be performed with short hospital stay and
      low morbidity, and achieve excellent durable results at 10 years.

PMID- 14583298
TI  - Usual and unusual locations of intrathoracic mesothelial cysts. Is endoscopic
      resection always possible?
AB  - OBJECTIVE: Mesothelial intrathoracic cysts are congenital lesions classically
      located in the anterior cardiophrenic angle (pleuro-pericardial cysts). Locations
      elsewhere in the thorax are infrequent. The aim of the study was to describe a 10
      year, single-institution experience with endoscopic management of mesothelial
      cysts by video-assisted thoracoscopy (VT) or video-assisted mediastinoscopy (VM),
      regardless of their location. METHODS: From January 1992 to December 2002, 13
      patients (four males and nine females, mean age 49.9 years, range 22-75)
      underwent surgery for a mesothelial cyst. Information on past history, clinical
      and radiological presentation, indications for surgery, the surgical procedure
      and postoperative outcome were collected retrospectively and inserted in a
      dedicated database. A follow-up visit was performed on December 2002 in all of
      the patients. RESULTS: In five patients the cyst was in the right cardio-phrenic
      angle, in three cases it was in the left cardiophrenic angle. Five cysts were
      located in the mediastinum (right paratracheal space in two cases, anterior
      mediastinum in one case, paravertebral mediastinum in two cases). Mean lesion
      diameter was 7.5 cm (+/-4) x 5 cm (+/-2). Cyst density ranged between 1 and 10
      Hounsfield units (HU) in 11 patients. It was respectively 38 and 52 UH in the
      other two patients. All patients were classed ASA 1 or 2 according to the
      guidelines of the American Society of Anesthesiologists (ASA). Indications for
      surgery included the presence of symptoms, uncertain diagnosis, practice of a
      particular sport or professional activity, and radiological evidence of
      compression of the superior vena cava (namely for the two paratracheal lesions).
      Eleven patients were operated on by VT. Two patients with a right paratracheal
      lesions were operated on by VM. Mean operating time was 60+/-14 min (range 45
      80). No postoperative complications were recorded. The mean postoperative stay
      was 4.3+/-1.2 days (5 days for VT and 2.5 days for VM). Pathology studies
      confirmed the diagnosis of mesothelial cyst in all cases. CONCLUSIONS:
      Mesothelial cysts have a heterogeneous distribution within the thorax, and nearly
      40% are located elsewhere than in the cardiophrenic angle. Endoscopic resection
      by VT or VM can be proposed as the treatment of choice even for mesothelial cysts
      in unusual locations.

PMID- 14583299
TI  - Pulmonary resection for massive hemoptysis of benign etiology.
AB  - OBJECTIVE: To assess the outcome of pulmonary resection in the management of
      massive hemoptysis caused by benign lung diseases. METHODS: A longitudinal cohort
      study of 53 consecutive patients who presented with hemoptysis and were treated
      with either emergency (group 1) or elective (group 2) pulmonary resection from
      January 1995 to December 1999. RESULTS: Fifty-three patients were studied, 27 in
      group 1 and 26 in group 2. The mean age of the patients was 47.2 years (range, 29
      70 years). Urgent examination with a combination of rigid and flexible fiberoptic
      bronchoscope localized the bleeding site in 45 patients (85%). Age>50 years,
      hypertension, hemoglobin on admission<10 g/dl, cause of hemoptysis, and a prior
      attack of hemoptysis were the predictors for the need of emergency surgery. The
      overall hospital mortality rate was 4% (2/53). Postoperative complications
      occurred in 13 patients (25%). Complications were more common in patients who
      received blood transfusion than non-transfused patients (9/23 and 4/30,
      respectively; P=0.03). Patients with tuberculosis as the cause of massive
      hemoptysis had more complications 5/8 in comparison to all other patients
      (P=0.02). The mean follow-up was 4.5 years (range, 3-6 years) for all patients
      who survived. Hemoptysis recurred in four patients (8%) and all from group 1
      (P=0.02). CONCLUSIONS: Immediate pulmonary resection for massive hemoptysis is
      effective in case of life-threatening bleeding that is not controlled by
      conservative measures. Elderly patients with a prior history of hemoptysis and/or
      hypertension and bleeding due to a fungus ball, necrotizing pneumonia,
      tuberculosis or lung abscess should be considered for early operation in an
      attempt to reduce morbidity and mortality.

PMID- 14583301
TI  - Surgical management of bronchiectasis: analysis and short-term results in 238
      patients.
AB  - OBJECTIVE: Bronchiectasis is defined permanent dilatations of bronchi with
      destruction of the bronchial wall. It is still a major cause of morbidity and
      mortality in developing countries. The aim of this retrospective study is to
      present our surgical experiences, the early and long-term results of 238 patients
      with bronchiectasis during a 10-year period. METHODS: We reviewed the medical
      records of 238 patients who underwent surgical resection for bronchiectasis
      between January 1992 and December 2001, at Gulhane Military Medical Academy
      (GMMA) Thoracic Surgery Department. Variables of age, sex, symptoms, etiology,
      and type of operation, mortality, morbidity and the result of surgical therapy
      were analyzed. RESULTS: There were 205 (86.13%) male and 33 (13.87%) female
      patients with an average age of 23.7 and a range of 15-48 years. The presenting
      symptoms were productive cough in 133 (55.88%), fetid sputum in 116 (48.73%),
      recurrent infections in 84 (35.29%), and hemoptysis in 39 (12.18%) patients. The
      disease was bilateral in 31 patients (13.02%) and mainly confined to the lower
      lobes in 162 (68.06%). The surgical treatment was as follows: pneumonectomy in 13
      patients (5.46%), lobectomy in 189 (79.40%), lobectomy+segmentectomy in 31
      (13.02%), and wedge resection or segmentectomy in five (2.1%). Staged bilateral
      thoracotomy was used in 14 patients. There was no operative mortality.
      Complications occurred in 21 patients and the morbidity rate was 8.82%. Complete
      resection was achieved in 154 (64.7%) patients. Follow-up data were obtained for
      229 (96.21%) of the patients. Nine patients were lost to follow-up. The mean
      follow-up of these patients was 9 months (range, 3 months to 4 years). The
      symptoms disappeared in 189 patients (79.41%) and 29 patients (12.18%) had
      improved, whereas 11 patients (4.62%) had no improvement. Significantly better
      results were obtained in patients who had undergone a complete resection.
      CONCLUSIONS: Surgical resection for bronchiectasis can be performed with
      acceptable morbidity and mortality at any age. The involved bronchiectatic sites
      should be resected completely for the optimum control of symptoms.

PMID- 14583300
TI  - The role of surgery in hemoptysis caused by thoracic actinomycosis; a forgotten
      disease.
AB  - OBJECTIVE: Thoracic actinomycosis is a relatively uncommon anaerobic infection
      caused by Actinomyces israelii. Rarely, it may be complicated by an unusual but
      significant hemoptysis manifestation. We describe our experiences of surgical
      treatment for hemoptysis in patients with pulmonary actinomycosis. METHODS: From
      1984 to 2002, 14 patients with thoracic actinomycosis and hemoptysis were
      diagnosed after thoracotomy. There were 11 male and three female patients with a
      mean age of 53.6 years. They all had non-specific symptoms and radiographic
      findings, and no case was an accurate diagnosis made at the time of hospital
      admission, including echo-guide aspiration, serial bronchoscopic biopsy and
      computed tomography biopsy. The indications of surgical intervention in our
      patients were for treating complications such as hemoptysis, chronic sinus
      discharge, or empyema, also limited to diagnostic purposes. Preoperative
      embolization was performed in seven cases; however, none was successful. RESULTS:
      Among the 14 patients, all the lesions were unilateral. The disease was confined
      to the lung in all patients; and chest wall involvement in one patient. The
      surgical procedures included were as follows: pneumonectomy (n=1), bilobectomy
      (n=1), lobectomy (n=10), wedge resection (n=2), and lung lesion with concomitant
      chest wall resection and chest wall reconstruction (n=1). Mean intraoperative and
      postoperative blood loss within the first 24 h was 192.3 ml, and five patients
      required blood transfusion. All of the specimens from the lesion site showed
      histological evidence of Actinomyces infection. All patients regularly took 12
      million units per day of intravenous crystalline penicillin G during their
      hospitalization, and oral procaine penicillin for up to 2 months. During the
      follow-up, all patients had an uneventful postoperative course. CONCLUSIONS: A
      high index of suspicion for this disease is advised for the surgeon engaged in
      the treatment of hemoptysis. Surgical resection of pulmonary actinomycosis is
      effective in preventing recurrence of hemoptysis. After diagnosis, it is treated
      using penicillin chemotherapy for at least 2 months.

PMID- 14583302
TI  - Longitudinal observation of antenatally detected congenital lung malformations
      (CLM): natural history, clinical outcome and long-term follow-up.
AB  - OBJECTIVE: The objective of the study is to present longitudinal observations in
      antenatally detected congenital lung malformations (CLM), particularly pulmonary
      sequestration (PS) and cystic adenomatoid malformation (CAM). METHODS: Fetuses
      found to have a CLM on prenatal ultrasound (US) were included in this study and
      followed up until delivery. In all newborns radiographs and computerized
      tomography (CT) studies of the thorax were performed. Surgical procedures
      included sequesterectomy, lobectomy, segmentectomy, and non-anatomic resection.
      Based on prenatal US findings, intrauterine course, postpartum chest radiographs
      and CT scans, as well as clinical signs and surgical findings patients were
      divided into six groups. RESULTS: Over a period of 6 years, routine prenatal US
      revealed suggestion of CLM in a series of 35 consecutive fetuses. In six cases
      pregnancy was terminated or the fetuses suffered fetal demise. Another four
      fetuses became symptomatic in utero when sequential scanning revealed hydrops,
      hydrothorax, and enlargement of cysts or polyhydramnios. Three cases in this
      group received serial therapeutic amniocentesis and serial puncture of either the
      hydrothorax or intrapulmonary cysts. After postpartum treatment in the intensive
      care unit surgical procedures were performed uneventfully and confirmed the
      diagnosis of CAM, PS or hybrid type lesions. In 11 patients US findings were
      considered to demonstrate spontaneous resolution of the lesion, but disappearance
      without sequelae could be confirmed only in six infants. Five infants were shown
      to have persistent CLM on postpartum CT scans. These infants underwent resection
      of the lesion within the first year of life. In 11 fetuses CLM were continuously
      demonstrated during pregnancy with only slight changes in size and structure.
      Postpartum the infants were asymptomatic and were subjected to a systematic plan
      of diagnostic work-up and treatment. Surgery in these infants revealed a large
      number of hybrid type lesions (n=5). In three infants, the primary diagnosis of
      PS or CAM had to be corrected during the diagnostic and therapeutic work-up.
      CONCLUSION: CLM are diagnosed antenatally with an increasing frequency and are
      shown to be quite different from previously applied concepts. The expected
      clinical outcome is far better than thought to be possible.

PMID- 14583303
TI  - Interventions in heart and thyroid surgery: can they be safely combined?
AB  - OBJECTIVE: Thyroid diseases are relatively common problems in patients with
      cardiac disease. The aim of this study was to evaluate the feasibility of
      combined interventions in heart and thyroid surgery. METHODS: A retrospective
      study of 2530 cardiac operations yielded six patients who underwent thyroid
      intervention combined with cardiac surgery (coronary artery bypass grafting,
      valvular surgery or both) between 1996 and 2003. All patients were examined for
      age, gender, cardiac problems, thyroid pathology and related symptoms. RESULTS:
      four males and two females were operated for coronary artery disease, valvular
      disease or both and for thyroid pathologies. All patients had anticoagulation
      with intravenous heparin peroperatively and then postoperatively. No patient
      suffered from bleeding at the neck neither per- or postoperatively. No
      hemodynamic or cardiovascular compromises were noted. CONCLUSION: The combined
      staged thyroid and cardiac surgery was feasible with a little risk for the both
      operations.

PMID- 14583304
TI  - Surgical results of patients with a functional single ventricle.
AB  - OBJECTIVE: Overall mortality of the patients with a functional single ventricle
      is still high, though excellent mid- and long-term results of the modified Fontan
      procedure have been reported. This study assessed the factors that affect the
      surgical outcomes mainly in the pre-Fontan stage and performed long-term survival
      analysis. METHODS: Between January 1988 and December 2000, 405 patients with a
      functional single ventricle underwent surgical interventions and were followed up
      until June 2001. The mean follow-up period was 74.5+/-69.4 months and 95% of the
      patients were followed up completely. Their median age was 2.5 months at the time
      of shunt or pulmonary artery banding (PAB), 8.6 months at BCPS, and 28.6 months
      at the Fontan operation. The variables of the anatomical lesions with single
      ventricle physiology, combined abnormalities, surgical pathways leading to the
      Fontan stage, age at operation, study periods, and type of the Fontan procedure
      were analyzed. The role of BCPS in the long-term results was evaluated. RESULTS:
      Overall survival after birth was 60.1+/-2.8% at 10 years. In multivariate
      analysis, complete atrioventricular septal defect-typed lesion, pulmonary venous
      obstruction, total anomalous pulmonary venous connection, and interruption of
      aortic arch were risk factors for long-term survival, while pulmonary stenosis
      was demonstrated as a favorable prognostic factor. In this study, there was no
      significant survival difference between the early and late study period.
      Actuarial mortality in the pre-Fontan stage was 41.3% in the non-BCPS group and
      16.3% in the BCPS group (P<0.001). The 10-year survival rates of the populations
      in staged and primary Fontan groups were not significantly different (P=0.24).
      The long-term survival rate of the atriopulmonary Fontan group was significantly
      lower than that of lateral tunnel Fontan (60.3+/-6.3% vs. 86.8+/-3.1% at 10
      years, P=0.0001). CONCLUSION: This study revealed that the overall survival was
      disappointing and there were still problems that need to be solved in the pre
      Fontan stage to improve the overall survival. The role of BCPS was not to
      contribute to the longer survival after Fontan operation, but to lower mortality
      in the pre-Fontan stage, which can offer a higher probability to proceed to the
      Fontan procedure successfully.

PMID- 14583305
TI  - Mortality after mitral regurgitation surgery: importance of clinical and
      echocardiographic variables.
AB  - OBJECTIVES: The management of patients with mitral regurgitation (MR) constitutes
      a challenge due to its heterogeneity in terms of etiology and possible treatment
      strategies. In the present study, we sought to describe the importance of
      preoperative echocardiographic and clinical variables in relation to outcome 5
      years after surgical treatment of MR. METHODS: The echocardiographic reports
      (transthoracic) from 298 patients were analyzed and the anatomic lesions were
      classified into one of three main groups (functional, organic degenerated with
      hypermobile valve or organic degenerated without hypermobility). 5-year
      cumulative survival was compared with the expected survival in an age- and gender
      matched normal population. Risk functions were determined with a Poisson
      regression model. RESULTS: Operative mortality was 4.4%, with higher mortality in
      patients with concomitant coronary artery bypass grafting (CABG) (7.6 vs. 2.2%,
      P=0.03). Survival after 5 years was 65% in patients with concomitant CABG,
      compared with the expected 86% (P<0.001), 70 vs. 88% (P<0.001) in patients with
      preoperative NYHA class III/IV, while survival in patients with NYHA class I/II
      did not differ from the expected (90 vs. 90%, P=0.56). In patients with a
      hypermobile valve without CABG, postoperative survival did not differ from the
      expected (91 vs. 89%, P=0.92). The estimated risk ratio for death, repair versus
      prosthesis, was 0.57 (95% confidence interval 0.32-1.00, P=0.05). CONCLUSIONS:
      The present study shows that it is possible, using transthoracic echocardiography
      and clinical data, to identify patients with an excellent outcome. The adverse
      effects of severe symptomatology and replacement compared with repair are
      demonstrated. The findings encourage early intervention before severe symptoms
      occur, especially if repair is possible.

PMID- 14583307
TI  - Outcome prediction in coronary artery bypass grafting and valve surgery in the
      Netherlands: development of the Amphiascore and its comparison with the
      Euroscore.
AB  - OBJECTIVES: (1) To define models that predict in-hospital death, major adverse
      cardiac events and extended intensive care unit duration for patients who
      underwent coronary artery bypass grafting (CABG), a heart valve operation or
      combined; and (2) to validate the Euroscore model in our population. METHODS:
      Data of all 7282 patient who underwent a CABG and/or heart valve operation in
      1997-2001 were prospectively collected. Three outcomes were examined: in-hospital
      death, major adverse cardiac events (MACE) and extended length of stay on
      intensive care (ELOS). Predicting models were made by multivariate logistic
      regression. The patient population was randomly divided in a derivation (two
      thirds) and a validation (one third) set. Area under the receiver operating
      characteristics curve (AUC) was used to study the discriminatory abilities of
      these models and the Euroscore. Hosmer-Lemeshow goodness-of-fit was used to study
      calibration of the predictive models. RESULTS: 2.4% of the patients died in
      hospital, 17% of the patients had a MACE and 14% had ELOS. The models for in
      hospital mortality and ELOS had a good validation (AUC 0.84 and 0.79,
      respectively). The validation for MACE was moderate (receiver-operating
      characteristic, ROC 0.67). All models were well calibrated. The validation of the
      Euroscore was as good as our model for in-hospital mortality (ROC 0.84).
      CONCLUSIONS: The Amphia score performs as well as the Euroscore in discriminating
      patients with respect to in-hospital death. Our models for predicting major
      adverse cardiac events and extended length of stay on intensive care may be
      useful tools in categorising patients in various subgroups of risk for
      postoperative morbidity.

PMID- 14583306
TI  - Cryoablation of the left posterior atrial wall: 95 patients and 3 years of mean
      follow-up.
AB  - OBJECTIVE: Endocardial ablation of the left atrial posterior wall has been used
      to treat atrial fibrillation. Aim of the study was to evaluate its efficacy
      looking for the ablation pattern allowing a fast execution with limited
      interference on atrial contractility. Moreover a statistical analysis to identify
      predictors of long-term sinus rhythm recovery has been provided. METHODS: From
      April 1998 to May 2002, 95 patients with permanent (mean duration 65 months) or
      persistent (33%) atrial fibrillation have undergone three different ablation
      patterns, only 1 patient being affected by lone atrial fibrillation. Mean antero
      posterior left atrial diameter was 76.2 mm. The prospective study collected
      information regarding variables related to patients' demographics, disease's
      characteristics and type of surgical ablation employed. Dependent variables were
      presence of sinus rhythm either at discharge and at 6 months. A logistic
      regression analysis was used to estimate the association between the collected
      variables and sinus rhythm restoration. RESULTS: In-hospital and late mortality
      rate were 3.2 and 6.3% respectively. At discharge 67 patients (72.8%) were in
      sinus rhythm while at a mean follow-up of 3 years, 81.4% of 86 surviving patients
      are in sinus rhythm. Major adverse events rate including cardiac reoperation,
      pace-maker implantation and cerebrovascular accident were 8.5, 6.3 and 4.2%,
      respectively. Pre-operative atrial fibrillation duration, left atrial dimension
      and type of mitral disease did not show any correlation with long term success
      while the lesion pattern and the rhythm at discharge were significant predictive
      factors. Survival is significantly higher in patients who converted to sinus
      rhythm at discharge (P=0.014) with respect to those who remained in atrial
      fibrillation. CONCLUSIONS: Permanent and persistent atrial fibrillation
      associated to a major cardiac disease can be safely treated with a linear
      ablation of the left atrial posterior wall. Satisfactory results in terms of
      rhythm restoration may be achieved regardless of the duration of the arrhythmia
      and its effects on atrial diameter. Any effort should be prompted to discharge
      patients in sinus rhythm. Life expectancy is longer if sinus rhythm is restored.

PMID- 14583308
TI  - Changes in health-related quality of life and functional capacity following
      coronary artery bypass graft surgery.
AB  - OBJECTIVE: Improvement in survival and quality of life are the primary
      indications for coronary artery bypass graft (CABG) operations. Among elderly
      patients the main goal of surgery is not necessarily to prolong life, but to
      improve the health-related quality of life. Factors associated with mortality and
      morbidity following CABG surgery have been well defined, but the quality of life
      and functional capacity in elderly patients undergoing CABG are poorly
      documented. The aim here was to investigate changes in health-related quality of
      life, overall performance status and symptomatic status during 1 year after CABG
      surgery. METHODS: Comprehensive data on 508 CABG patients were prospectively
      collected, including preoperative risk factors and postoperative morbidity in a
      surgical center and in all eighteen secondary referral hospitals up to discharge.
      The RAND-36 Health Survey (RAND-36) was used as indicator of quality of life. The
      primary outcome was change in the physical component summary, mental component
      summary and General Health summary scores from the RAND-36. Karnofsky dependency
      category was used to assess overall performance status, and symptomatic status
      was estimated according to New York Heart Association (NYHA) class. All
      assessments were made preoperatively and repeated 12 months later. Analysis was
      based on three age groups: 64 years or less (282 patients), 65-74 years (175
      patients), and 75 or more years (51 patients). RESULTS: Thirty-day and 1-year
      survival rates were 98.2 and 96.7%, respectively. A great majority (86.4%) of the
      patients recovered without major complication. In all, the present data showed
      significant improvement in all eight domains of QOL as well as in functional
      capacity and NYHA class during the 1st year after CABG. However, the mean change
      in RAND-36 Mental Component Summary scores among patients aged 75 years or more
      did not reach a statistically significant level (P=0.097) and they had
      significantly minor improvement as compared to younger patients (P<0.05).
      Moreover, their General Health score improvement was poorer and statistically
      insignificant (P=0.817). CONCLUSIONS: Elderly patients not only have higher
      mortality and morbidity but also derive less benefit from CABG regarding certain
      aspects of QOL.

PMID- 14583309
TI  - Acute effects of tourniquet occlusion and intraluminal shunts in beating heart
      surgery.
AB  - OBJECTIVE: MIDCAB and OPCAB revascularization is currently performed with
      temporary tourniquet occlusion of the coronary artery to achieve a bloodless
      surgical field. However, a trauma of the vessel wall due to snaring sometimes
      occurs. The use of temporary intraluminal shunts (TILS) have recently been
      advocated as an alternative. The aim of this experimental study was to evaluate
      the acute ultrastructural effects of TILS versus tourniquet occlusion on the
      coronary vessel wall. METHODS: Twelve pigs (40+/-3 kg) were investigated. In
      group A (n=6) the left anterior descending (LAD) artery was temporarily occluded
      with a tourniquet over 20 min. In group B (n=6) a commercially available silicone
      TILS (1.5-mm diameter, 12-mm length, AnastaFlo, Research Medical Inc.) was placed
      in the LAD. After 20 min perfusion the TILS was removed and the insertion was
      repaired. After 30 min reperfusion all animals were killed. Three LAD territories
      of each animal were examined histopathologically by scanning electron microscopy
      (SEM), light microscopy (LM) and transmission electron microscopy (TEM). Areas of
      occlusion or placement of the TILS olives were investigated. RESULTS: SEM
      revealed ultrastructural alterations in both groups. While marked intimal rupture
      appeared in all animals of group A, only two of the six animals of group B
      exhibited superficial endothelial abrasions. LM showed differences of intimal
      thickness in all groups while TEM revealed severe edema of subendothelial tissue
      in four of six animals in group A. CONCLUSION: The intimal lesions observed after
      tourniquet occlusion in our experimental off-pump surgery model confirmed other
      recent studies. In contrast, utilization of TILS caused only minor damage of the
      vessel wall. The endothelial abrasions detected in this group may be a
      consequence of micro-dislocations or insertion maneuvers. Chronic studies are
      necessary to verify as to whether the mild injury after TILS insertion will
      result in a reduction or even absence of de-novo stenoses compared with
      tourniquet occlusion.

PMID- 14583310
TI  - Right heart assist for beating heart coronary artery bypass grafting.
AB  - OBJECTIVE: Cardiopulmonary bypass used in conventional coronary artery bypass
      surgery (cCABG) entails a risk of complications. Consequently, the trend is
      moving towards off-pump coronary artery bypass (OPCAB). This procedure, however,
      may lead to haemodynamic instability due to kinking of the right ventricle when
      the posterior aspect of the heart is exposed. The aim of the study was to
      establish if a right-sided circulatory assist device (RHA) was able to maintain
      haemodynamic stability during OPCAB procedures. METHOD: In a prospective study 50
      RHA-OPCAB patients and a control group of 50 cCABG patients were examined. Before
      accessing the marginal arteries, an RHA was established in the RHA-OPCAB
      patients. RESULTS: A stable haemodynamic condition was achieved for 98% of the
      RHA-OPCAB patients. The study group had less postoperative chest drain bleeding
      (P<0.001), shorter ventilation time (P=0.001), and lower blood levels of creatine
      kinase (CK) and brain CK (P<0.001) compared to the control group. CONCLUSION: The
      results indicate that RHA-OPCAB is a realistic alternative to cCABG. The
      procedure can be safely performed most likely resulting in reduced postoperative
      bleeding, myocardial damage, and ventilation time.

PMID- 14583311
TI  - Prophylactic milrinone during OPCAB of posterior vessels: implication in angina
      patients taking beta-blockers.
AB  - OBJECTIVE: To determine whether a phosphodiesterase type 3 inhibitor can improve
      hemodynamics during off-pump coronary artery bypass grafting (OPCAB) of posterior
      vessels in patients on beta(1)-adrenoreceptor blockers. METHODS: Thirty patients
      scheduled for OPCAB of the obtuse marginal artery (OM), and taking atenolol 100
      mg a day were randomized in a double-blind manner to receive either milrinone or
      placebo. Hemodynamic data were obtained after induction, before pericardial
      incision, during left anterior descending artery grafting, during OM grafting,
      and after removal of the stabilizer. During the OM grafting, dopamine was infused
      when the cardiac index (CI) decreased below 2.0 L/min/m(2), and phenylephrine was
      infused to maintain the arterial pressure with a CI above 2.0 L/min/m(2).
      RESULTS: During OM anastomosis, there were significant differences in CI
      (milrinone [M] = +7.7%, control [C] = -13.7%, p=0.01), SVI (M=-21.5%, C=-35.8%,
      p=0.03), SvO(2) (M=-2.6%, C=-8.9%, p=0.02), and SVR (M=-28.1%, C=+1.1%, p=0.01)
      between the two groups, in terms of percentage change from baseline value.
      Dopamine was required more frequently and at a higher dose in the control group
      (M=13%, 5.0 microg/kg/min; C=67%, 10.1 microg/kg/min, p<0.05). Phenylephrine was
      infused in 33% of the patients in the milrinone group compared to 13% in the
      control group (p>0.05). CONCLUSIONS: Prophylactic milrinone improves CI, SVI and
      SvO(2) reducing the need for high doses of dopamine during OM anastomosis in
      patients taking atenolol. Therefore, it can be used as an alternative to dopamine
      improving hemodynamics and organ perfusion during OPCAB of posterior vessels in
      patients on beta(1)-blockers.

PMID- 14583312
TI  - Mitochondrial DNA deletions in coronary artery bypass grafting patients.
AB  - OBJECTIVE: Mitochondrial DNA (mitoDNA) deletions have been shown to increase with
      aging and ischemia and have been suggested to contribute to myocardial
      dysfunction. The purpose of this study was to determine the prevalence and
      specificity of mitoDNA deletions in coronary artery bypass patients. METHODS:
      Right atrial appendix tissue from 51 cardiac surgical patients (30-93 years; mean
      64+/-14 years) was obtained during cardiopulmonary bypass cannulation (Control),
      just prior to the removal of the venous cannula (Ischemia, 169+/-38 min) and
      following removal of the cannula (Reperfusion) and used for polymerase chain
      reaction (PCR) and sequence analysis. RESULTS: A novel mitoDNA deletion
      (approximately 7.3 kb, mitoDNA(7.3)) was found in three unrelated, male patients
      (53, 67, 75 years old). All mitoDNA(7.3) deletion breakpoints were found
      downstream of the ATP synthase 8 genes and at the 3' end of the cytochrome b
      genes. The prevalence of the mitoDNA(7.3) deletion was significantly increased
      (P<0.05) following ischemia and reperfusion. Clinical data indicated that
      postoperative left ventricular ejection fraction was lower (38.3 vs. 46.4%), and
      the incidence of previous myocardial infarction higher (1.7 vs. 0.6) in patients
      exhibiting mitoDNA deletions. CONCLUSION: Our results reveal a novel
      mitochondrial DNA deletion occurring within the genome region coding for the
      mitochondrial genes of oxidative phosphorylation that is significantly increased
      during ischemia and reperfusion. The incidence and prevalence of mitoDNA(7.3)
      deletions in patients with clinical indications of poor recovery suggests that
      mitoDNA(7.3) deletions may provide an important indicator to surgical outcome in
      the cardiac surgical patient.

PMID- 14583313
TI  - Gene therapy in cardiac surgery: intramyocardial injection of naked plasmid DNA
      for chronic myocardial ischemia.
AB  - OBJECTIVE: Growth factor gene therapy represents one current approach in the
      therapy of myocardial ischemia. We assessed the in vitro and in vivo expression
      of naked plasmid DNA aiming at preservation of function in a chronically ischemic
      myocardial model. METHODS: In vitro: Primary cardiac fibroblasts were transfected
      with plasmids encoding enhanced green fluorescent protein, human VEGF(121), human
      FGF-2, or porcine MCP-1. Protein synthesis was assessed microscopically, by
      ELISA, Western blotting, or intracellular immunofluorescence. In vivo: A LAD
      stenosis was created in healthy pigs. One week later, segmental myocardial
      shortening (SMS) and systemic hemodynamics (left ventricular stroke work index,
      LVSWI, time derivative of left ventricular pressure, dp/dt(max)) were assessed at
      baseline. Afterwards, the ischemic area received either intramyocardial
      injections of naked cytokine plasmid DNA or vector only, or was left untreated.
      One myocardial sample taken 1 h after plasmid injection was subjected to RT-PCR
      and PCR. After 3 months, cardiac function was re-examined. RESULTS: In vitro:
      Transfection of cardiac fibroblasts resulted in high gene expression for several
      days. In vivo: Plasmid-specific DNA and mRNA were found 1 h after plasmid
      injection (n=1). After 3 months, VEGF, FGF-2, and vector rendered better results
      of regional contractility at rest and of LVSWI. However, only VEGF and FGF-2 were
      effective with regard to regional contractility under dobutamine stress and to
      left ventricular contractility. CONCLUSION: In conclusion, intramyocardial
      injection of naked plasmid DNA encoding VEGF(121) or FGF-2 improved myocardial
      function in chronic ischemia in more aspects than vector only and was superior to
      untreated ischemia or MCP-1. This strategy can be considered a successful tool
      for growth factor stimulated preservation of function in chronic myocardial
      ischemia.

PMID- 14583314
TI  - Gene transfer of cytoprotective and immunomodulatory molecules for prevention of
      cardiac allograft rejection.
AB  - Current treatments of heart transplantation are limited by incomplete
      effectiveness, significant toxicity, and failure to prevent chronic rejection.
      Genetic manipulation of the donor heart at the time of removal offers the unique
      opportunity to produce a therapeutic molecule within the graft itself, while
      minimizing systemic effects. Cytoprotective approaches including gene transfer of
      heme oxygenase (HO)-1, endothelial nitric oxide synthase, and antisense
      oligodeoxynucleotides specific for nuclear factor (NF)-kappa B or intercellular
      adhesion molecule (ICAM)-1 reduced ischaemia-reperfusion injury and delayed
      cardiac allograft rejection in small animals. Exogenous overexpression of
      immunomodulatory cytokines such as interleukin (IL)-4, IL-10 and transforming
      growth factor-beta, as well as gene transfer of inhibitors of pro-inflammatory
      cytokines also delayed graft rejection. Gene transfer-based blockade of T-cell
      costimulatory activation with CTLA4-Ig or CD40-Ig resulted in long-lasting graft
      survival and donor-specific unresponsiveness, as manifested by acceptance of a
      second graft from the original donor strain but rejection of third-party grafts.
      Similar results were obtained with donor major histocompatibility complex class I
      gene transfer into bone marrow cells. Gene therapy approaches to chronic
      rejection included gene transfer of HO-1, soluble Fas, tissue plasminogen
      activator and antisense oligodeoxynucleotides specific for the anti-apoptotic
      mediator Bcl-x or the E2F transcription factor. Despite major experimental
      advances, however, gene therapy for heart transplantation has not entered the
      clinical arena yet. Fundamental questions regarding the most suitable vector, the
      best gene, and safety issues remain unanswered. Well-controlled studies that
      compare gene therapy with established treatments in non-human primates are needed
      before clinical trials can be started.

PMID- 14583316
TI  - Importance of extrasegmental vessels for spinal cord blood supply in a chronic
      porcine model.
AB  - OBJECTIVE: Our purpose was to investigate the interaction of the important
      components of spinal cord blood supply in the pig model to enable its use for
      future studies of spinal cord protection. METHODS: Twenty-five juvenile pigs (20
      22 kg) underwent serial intercostal (IC) or lumbar artery (LA) ligation until
      disappearance of motor evoked potentials (MEPs). Pigs underwent sequential
      craniocaudal IC/LA ligation alone (n=5); following clamping of both subclavian
      arteries (n=4), or clamping of the median sacral artery (MSA, n=4). Animals also
      underwent serial caudocranial clamping of LA/IC alone (n=4); preceded by clamping
      of the subclavian arteries (n=4), or of the MSA (n=4). Results were verified by
      Tarlov's scores and perioperative angiography. RESULTS: All animals with MEP loss
      suffered postoperative paraplegia. Groups were equivalent with regard to stable
      arterial pressures (64.6+/-3.1 degrees C) throughout the experiment, temperature
      (36+/-1.1 degrees C) and other physiological parameters. Mean number of clamped
      IC/LA before MEP loss for cranio-caudal clamping direction was 12.8+/-0.8 for
      segmental arteries isolated, 9+/-0.8 if both subclavian arteries were ligated
      previously and only 4.3+/-0.5 IC if the median sacral artery was clamped before.
      Mean number of clamped LA for caudo-cranial clamping direction was 5.8+/-0.9 for
      segmental lumbar arteries, 5.5+/-0.6 LA if both subclavian arteries were ligated
      previously and 3.5+/-0.6 if the median sacral artery was clamped before.
      CONCLUSION: This study confirms the importance of lumbar and MSA arteries to cord
      viability. It documents the interaction of the subclavian and MSA (roughly
      equivalent to the hypogastric arteries in humans) with segmental vessels in
      providing spinal cord blood supply. It also provides the physiologic basis for
      use of the pig model for studies of spinal cord protection in aortic surgery.

PMID- 14583315
TI  - Impact of hypothermic selective cerebral perfusion compared with hypothermic
      cardiopulmonary bypass on cerebral hemodynamics and metabolism.
AB  - OBJECTIVE: Hypothermic selective cerebral perfusion (SCP) is widely used for
      cerebral protection during aortic arch surgery, but the effect of the absence of
      systemic perfusion on cerebrovascular dynamics it has never been established.
      This study explored the physiology of prolonged SCP compared to hypothermic
      cardiopulmonary bypass (HCPB) in pigs. METHODS: In this blinded protocol, 29
      juvenile pigs (20-23 kg) were randomized after cooling on cardiopulmonary bypass
      (CPB) to 20 degrees C. Group I pigs (n=14) underwent 90 min of SCP, while group
      II (HCPB, n=15) underwent total body perfusion. Fluorescent microspheres were
      injected during perfusion and recovery, enabling calculation of total and
      regional cerebral blood flow (CBF). Cerebrovascular resistance (CVR), oxygen
      consumption and intracranial pressure (ICP) were also monitored. RESULTS: CBF
      decreased significantly (P=0.0001) during cooling, but remained at significantly
      higher levels with SCP than with HCPB throughout perfusion and recovery
      (P<0.0001). CVR was significantly lower with SCP than with HCPB throughout
      perfusion (P=0.04). Oxygen consumption fell significantly with cooling
      (P=0.0001), remained low during perfusion, and rebounded promptly with rewarming;
      with SCP it was significantly higher than with HCPB throughout the perfusion
      interval (P=0.03), and remained higher thereafter. ICP rose significantly less
      with SCP than with HCPB (P=0.02). CONCLUSION: We conclude that, compared with
      HCPB, SCP results in beneficial cerebral vasodilatation, as evidenced by
      significantly higher CBF and oxygen consumption during SCP, by prompt recovery of
      oxygen consumption after rewarming, and by significantly lower ICP during
      perfusion and in the post-bypass period.

PMID- 14583317
TI  - Giant chest wall tumor.

PMID- 14583318
TI  - Multiple bilateral recurrent neurofibromas of the lungs.

PMID- 14583319
TI  - Intraoperative transesophageal echocardiographic assessment of myocardial
      protection in a redo ascending-arch aortic operation.
AB  - In a redo operation of the ascending aortic arch, transesophageal
      echocardiography was useful in confirming antegrade infusion flow of cardioplegia
      solution into the left main coronary artery.

PMID- 14583320
TI  - Coronary artery spasm after off-pump coronary artery by-pass grafting.
AB  - The immediate postoperative period of patients undergoing off-pump coronary
      artery by-pass grafting can be severely complicated by unsuspected coronary
      artery spasm. A case of right coronary artery spasm possibly induced by
      myocardial stabilisation technique is presented.

PMID- 14583321
TI  - A new right ventricular assist device for right ventricular support.
AB  - Right ventricular support by mechanical devices for postcardiotomy right heart
      failure is still associated with a high mortality. We report on the first use of
      a new paracardiac microaxial blood pump for postcardiotomy right heart failure in
      two patients undergoing emergency coronary artery bypass grafting (the first
      patient for a myocardial infarction complicated by a left ventricular wall
      rupture, the second patient for a dissection of the right coronary artery after
      an interventional procedure).

PMID- 14583322
TI  - Successful weaning from inhaled nitric oxide using dipyridamole.
AB  - A 33-year-old woman with an atrial septal defect associated with severe pulmonary
      hypertension underwent suture closure of the defect after assessment of
      operability by lung biopsy. Postoperative course was complicated by suprasystemic
      refractory pulmonary hypertension, and she became dependent upon treatment with
      inhaled nitric oxide. After multiple attempts to withdraw nitric oxide,
      dipyridamole was administered and blunted the rebound pulmonary hypertension
      after subsequent nitric oxide withdrawal.

PMID- 14583323
TI  - Surgical resection of right atrial neurilemoma extending to pulmonary vein.
AB  - An asymptomatic cardiac neurilemoma was found in a 33-year-old woman. The tumor
      was on the anterior surface of the right atrium extending to the right upper
      pulmonary vein across the interatrial groove. The tumor was resected completely
      and right atrium, interatrial septum, left atrium and right superior pulmonary
      vein were reconstructed with cardiopulmonary bypass. The patient recovered
      uneventfully and had no recurrence 1 year after the operation. We reviewed ten
      reported cases of cardiac neurilemoma, including our patient.

PMID- 14583324
TI  - Surgical clearance of invasive cardiac leiomyosarcoma with concomitant
      pneumonectomy.
AB  - The management of cardiac leiomyosarcoma is still controversial. Due to the rare
      occurrence and late presentation of such tumours the treatment is essentially
      palliative. We report on a case in a young female who presented with catastrophic
      haemodynamic instability and pulmonary venous obstruction by a large mass in her
      left atrium. Right pneumonectomy was performed as part of emergency surgery in
      this patient with a left atrial tumour of unknown histology. We feel that an
      attempt at complete clearance of these tumours is justified, as surgery remains
      the only chance of long-term survival. Postoperatively, adjuvant chemotherapy
      and/or radiotherapy may have a role.

PMID- 14583325
TI  - Purulent pericarditis caused by malignant oesophago-pericardial fistula.
AB  - A case of purulent pericarditis with an unusual aetiology and a favourable
      outcome is reported. This patient presented with purulent pericarditis secondary
      to an oesophago-pericardial fistula caused by a squamous carcinoma of the
      oesophagus. A review of the literature revealed only a small number of similar
      cases. The prognosis can be improved by rapid diagnosis, appropriate antibiotic
      therapy, surgical drainage and surgical repair of the fistula. An aggressive
      therapeutic approach should be proposed in order to achieve long-term remission
      in these frequently young patients.

PMID- 14583326
TI  - Surprising outcome similarities between Contegra bovine jugular vein conduit and
      Shelhigh No-React porcine pulmonary valve conduit: role of immunologic reaction.

PMID- 14583328
TI  - The role of early ischemic preconditioning in spinal cord protection after
      transient aortic occlusion.

PMID- 14583334
TI  - Cigarette smoke triggers macrophage adhesion and activation: role of lipid
      peroxidation products and scavenger receptor.
AB  - Pulmonary emphysema in chronic obstructive pulmonary disease (COPD) is
      characterized by the destruction of the alveolar walls leading to permanent
      enlargement of distal respiratory air spaces. A major causal factor is cigarette
      smoking, which produces conditions of chronic oxidative stress within the lungs.
      At a cellular level, increased macrophage accumulation and retention within the
      alveolar interstitial spaces is pivotal to the development of emphysema. To date
      it has been unclear as to the underlying mechanisms relating chronic oxidative
      stress to macrophage accumulation and retention. Our study was initiated to
      ascertain the role of modification of extracellular matrix proteins with
      cigarette smoke and products of lipid peroxidation on macrophage adhesion and
      activation. Increased numbers of macrophages were seen adhering to cigarette
      smoke-modified collagen IV as compared to unmodified collagen, where little or no
      adherent macrophages were observed. Similar observations were made when collagen
      was modified with either acrolein or 4-hydroxy-2-nonenal. Adhesion could be
      blocked with either fucoidan or a monoclonal antibody against the Type A
      macrophage scavenger receptor. Also, modified collagen triggered both oxidative
      burst and MCP-1 release in macrophages. These results, therefore, highlight a
      potential mechanism by which oxidative stress through the production of reactive
      carbonyls promotes macrophage accumulation, retention, and activation,
      independently of other proinflammatory stimuli. The implications of this for the
      development of emphysema in COPD are discussed.

PMID- 14583335
TI  - Acute angiotensin II increases plasma F2-isoprostanes in salt-replete human
      hypertensives.
AB  - Angiotensin (Ang) II induces oxidative stress in vitro and in animal models of
      hypertension. We tested the hypothesis that Ang II increases oxidative stress in
      human hypertension, as assessed by plasma F2-isoprostane concentrations. Plasma
      F2-isoprostanes, hemodynamic and endocrine parameters were measured at baseline
      and following a 55 min infusion of 3 ng/kg/min Ang II in 13 normotensive and 13
      hypertensive volunteers ingesting a high- (200 mmol/d) or low- (10 mmol/d) sodium
      diet. Mean arterial pressure (MAP) and body mass index were higher in
      hypertensive subjects. Ang II infusion increased MAP (p<.001) and plasma
      aldosterone concentrations (p<.001) and decreased plasma renin activity (p<.001)
      and renal plasma flow (p<.001) to a similar extent in both groups. Plasma F2
      isoprostane concentrations were similar at baseline. There was no effect of Ang
      II on F2-isoprostane concentrations during low-salt intake in either group
      (normotensive 51.7 +/- 7.1 to 53.7 +/- 6.5 pg/ml and hypertensive 52.2 +/- 8.2 to
      56.2 +/- 10.0 pg/ml; mean +/- SE). During high-salt intake, Ang II increased F2
      isoprostane concentrations in the hypertensive group (52.3 +/- 7.2 to 63.2 +/-
      10.4 pg/ml, p=0.010) but not in the normotensive group (54.2 +/- 4.4 to 58.9 +/-
      6.6 pg/ml, p=0.83). Acute Ang II infusion increases oxidative stress in vivo in
      hypertensive humans. The renin-angiotensin system may contribute to oxidative
      stress in human cardiovascular disease.

PMID- 14583336
TI  - Endosomal and lysosomal effects of desferrioxamine: protection of HeLa cells from
      hydrogen peroxide-induced DNA damage and induction of cell-cycle arrest.
AB  - The role of endosomal/lysosomal redox-active iron in H2O2-induced nuclear DNA
      damage as well as in cell proliferation was examined using the iron chelator
      desferrioxamine (DFO). Transient transfections of HeLa cells with vectors
      encoding dominant proteins involved in the regulation of various routes of
      endocytosis (dynamin and Rab5) were used to show that DFO (a potent and rather
      specific iron chelator) enters cells by fluid-phase endocytosis and exerts its
      effects by chelating redox-active iron present in the endosomal/lysosomal
      compartment. Endocytosed DFO effectively protected cells against H2O2-induced DNA
      damage, indicating the importance of endosomal/lysosomal redox-active iron in
      these processes. Moreover, exposure of cells to DFO in a range of concentrations
      (0.1 to 100 microM) inhibited cell proliferation in a fluid-phase endocytosis
      dependent manner. Flow cytometric analysis of cells exposed to 100 microM DFO for
      24 h showed that the cell cycle was transiently interrupted at the G2/M phase,
      while treatment for 48 h led to permanent cell arrest. Collectively, the above
      results clearly indicate that DFO has to be endocytosed by the fluid-phase
      pathway to protect cells against H2O2-induced DNA damage. Moreover, chelation of
      iron in the endosomal/lysosomal cell compartment leads to cell cycle
      interruption, indicating that all cellular labile iron is propagated through this
      compartment before its anabolic use is possible.

PMID- 14583337
TI  - Endothelial NO synthase phosphorylated at SER635 produces NO without requiring
      intracellular calcium increase.
AB  - Shear stress stimulates NO production involving the Ca2+-independent mechanisms
      in endothelial cells. We have shown that exposure of bovine aortic endothelial
      cells (BAEC) to shear stress stimulates phosphorylation of eNOS at S635 and S1179
      by the protein kinase A- (PKA-) dependent mechanisms. We examined whether
      phosphorylation of S635 of eNOS induced by PKA stimulates NO production in a
      calcium-independent manner. Expression of a constitutively active catalytic
      subunit of PKA (Cqr) in BAEC induced phosphorylation of S635 and S1179 residues
      and dephosphorylation of T497. Additionally, Cqr expression stimulated NO
      production, which could not be prevented by treating cells with the intracellular
      calcium chelator BAPTA-AM. To determine the role of each eNOS phosphorylation
      site in NO production, HEK-293 cells transfected with eNOS point mutants whereby
      S116, T497, S635, and S1179 were mutated to either A or D. Maximum NO production
      from S635D-expressing cells was significantly higher than that of either wild
      type or S635A in both basal and elevated [Ca2+]i conditions. More interestingly,
      S635D cells produced NO even when [Ca2+]i was nearly depleted by BAPTA-AM. We
      confirmed these results obtained in HEK-293 cells in BAEC transfected with S635D,
      S635A, or wild-type eNOS vector. These findings suggest that, once phosphorylated
      at S635 residue, eNOS produces NO without requiring any changes in [Ca2+]i. PKA
      dependent phosphorylation of eNOS S635 and subsequent basal NO production in a
      Ca2+-independent manner may play an important role in regulating vascular biology
      and pathophysiology.

PMID- 14583338
TI  - Overexpression of PHGPx and HSP60/10 protects against ischemia/reoxygenation
      injury.
AB  - Reactive oxygen species arising from ischemia/reperfusion (I/R) cause damage to
      cardiac tissue. We examined the effects of mitochondrial phospholipid
      hydroperoxide glutathione peroxidase (mPHGPx) and cytosolic PHGPx (cPHGPx)
      overexpression on protection against simulated I/R in neonatal rat cardiac
      myocytes (NCM). Additionally, a protective combinatorial effect with heat shock
      proteins 60 and 10 (HSP60/10) was investigated. NCM were infected with adenoviral
      vectors expressing mPHGPx, cPHGPx, HSP60/10, or an empty control (Adv-) and
      submitted to 8 h of ischemia followed by 16 h of reoxygenation. mPHGPx infection
      led to a 40% decrease in malondialdehyde and 4-hydroxy-2(E)-nonenal following I/R
      (p<.05). Creatine kinase and lactate dehydrogenase release were decreased in both
      mPHGPx-infected and HSP60/10-infected cells (p<.05). The combination of mPHGPx
      and HSP60/10 overexpression led to further protection (p<.01). DNA laddering and
      histone-associated DNA fragments were decreased in PHGPx- and HSP60/10-infected
      cells (p<.01). Cytochrome c release from mitochondria was decreased in mPHGPx
      infected cells. Furthermore, mPHGPx overexpression preserved electron transport
      chain complex IV function following simulated I/R (p<.05). These results indicate
      that overexpression of PHGPx provides protection against damage resulting from
      simulated I/R injury, particularly in the mitochondria, and that the combination
      of mPHGPx and HSP60/10 imparts an added protective effect.

PMID- 14583339
TI  - Reaction of cysteine and glutathione (GSH) at the freshly fractured quartz
      surface: a possible role in silica-related diseases?
AB  - The reactivity of quartz dusts towards glutathione (GSH) and cysteine (Cys) has
      been investigated. Cys and GSH react, without being adsorbed (UV-Vis
      spectroscopy), with commercial quartz dusts in an exposed surface-dependent way,
      but not with amorphous silica. GSH and Cys have been contacted with freshly
      ground quartz (agate jar QZg-a and steel jar QZg-s) and quartz heated in air at
      500 degrees C (QZs-500) and with a dust generated from a purified quartz
      (99.9999%) to detect the nature of the reacting surface sites. With both GSH and
      Cys, the highest reactivity was found on the particles ground in a steel jar,
      while pure quartz was fully inactive. Detection of the radical GS* (spin
      trapping) suggests a radical mechanism of oxidation to disulphide onto surface
      bound iron traces, more abundant on QZg-s and absent on the pure quartz.
      Oxidation of thiol groups occurs at surface sites different from those involved
      in the homolytic rupture of a C-H bond. Both reactions are more pronounced on
      freshly ground samples, but the C-H rupture takes place at silicon-based surface
      radicals and Fe2+ centers, while oxidation of GSH and Cys requires Fe3+ centers.
      As all commercial quartz dusts contain surface iron as an impurity, depletion of
      extracellular or intracellular GSH may contribute to the oxidative damage caused
      by particle-derived and cell-derived reactive oxygen species.

PMID- 14583340
TI  - Enhanced bleomycin-induced pulmonary damage in mice lacking extracellular
      superoxide dismutase.
AB  - Extracellular superoxide dismutase (EC-SOD) is highly expressed in the
      extracellular matrix of lung and vascular tissue. Localization of EC-SOD to the
      matrix of the lung may protect against oxidative tissue damage that leads to
      pulmonary fibrosis. This study directly examines the protective role of EC-SOD in
      a bleomycin model of pulmonary fibrosis and the effect of this enzyme on
      oxidative protein fragmentation. Mice null for ec-sod display a marked increase
      in lung inflammation at 14 d post-bleomycin treatment as compared to their wild
      type counterparts. Hydroxyproline analysis determined that both wild-type and ec
      sod null mice display a marked increase in interstitial fibrosis at 14 d post
      treatment, and the severity of fibrosis is significantly increased in ec-sod null
      mice compared to wild-type mice. To determine if the lack of EC-SOD promotes
      bleomycin-induced oxidative protein modification, 2-pyrrolidone content (as a
      measure of oxidative protein fragmentation at proline residues) was assessed in
      lung tissue from treated mice. 2-Pyrrolidone levels in the lung hydrolysates from
      ec-sod null mice were increased at both 7 and 14 d post-bleomycin treatment as
      compared to wild-type mice, indicating EC-SOD can inhibit oxidative fragmentation
      of proteins in this specific model of oxidative stress.

PMID- 14583341
TI  - Effect of eicosapentaenoic acid and docosahexaenoic acid on oxidative stress and
      inflammatory markers in treated-hypertensive type 2 diabetic subjects.
AB  - n-3 fatty acids reduce the risk of cardiovascular disease via a number of
      possible mechanisms. Despite this, there has been concern that these fatty acids
      may increase lipid peroxidation. The data in vivo are inconclusive, due in part
      to limitations in the methodologies. In this regard, the measurement of F2
      isoprostanes provides a reliable assessment of in vivo lipid peroxidation and
      oxidant stress. This study aimed to assess the effects of supplementation with
      purified eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA), the two major
      n-3 fatty acids, on urinary F2-isoprostanes and markers of inflammation, in type
      2 diabetic patients. In a double-blind, placebo controlled trial of parallel
      design, 59 nonsmoking, treated-hypertensive, type 2 diabetic subjects, were
      randomized to 4 g daily of purified EPA, DHA, or olive oil for 6 weeks, while
      maintaining their usual diet. F2-isoprostanes, measured using gas chromatography
      mass spectrometry in 24 h urines and C-reactive protein (CRP), interleukin-6 (IL
      6) and tumor necrosis factor-alpha (TNF-alpha), were measured before and after
      intervention. Thirty-nine men and 12 women aged 61.2 +/- 1.2 years, with body
      mass index (BMI), 29.5 +/- 0.5 kg/m2; 24 h blood pressure, 138/73 mmHg; HbA1c,
      7.3 +/- 0.1% and fasting glucose, 7.9 +/- 0.2 mmol/l completed the intervention.
      Baseline urinary F2-isoprostanes were positively associated with HbA1c (p=.011)
      and fasting glucose (p=.032). Relative to the olive oil group, postintervention
      urinary F2-isoprostanes were decreased 19% by EPA (p=.017) and 20% by DHA
      (p=.014). There were no significant changes in CRP, IL-6, and TNF-alpha following
      EPA or DHA supplementation. In regression analysis, Delta F2-isoprostanes were
      positively associated with Delta HbA1c (p=.007) independent of treatment group;
      and with Delta TNF-alpha (p=.034) independent of age, gender, BMI, and treatment
      group. There were no associations with Delta CRP or Delta IL-6. This study is the
      first report demonstrating that either EPA or DHA reduce in vivo oxidant stress
      without changing markers of inflammation, in treated hypertensive, type 2
      diabetic subjects.

PMID- 14583342
TI  - Oxygen radical-dependent expression of CXC chemokines regulate
      ischemia/reperfusion-induced leukocyte adhesion in the mouse colon.
AB  - Activation and accumulation of leukocytes constitute a rate-limiting step in
      ischemia/reperfusion (I/R)-induced tissue injury. The signalling mechanisms,
      however, that regulate leukocyte rolling and adhesion in the colonic
      microcirculation are not known. The objective of the study was to define the role
      of CXC chemokines (MIP-2 and KC) in I/R-induced leukocyte-endothelial cell
      interactions in the mouse colon. In C57/B16 mice, colonic ischemia was induced by
      clamping the superior mesenteric artery for 30 min and leukocyte rolling and
      stationary adhesion were examined in venules after 120 and 240 min of
      reperfusion. I/R provoked a clear-cut increase in leukocyte rolling and adhesion
      in colonic venules. Both MIP-2 and KC were upregulated at the gene and protein
      level in the reperfused colon. Immunoneutralization of MIP-2 and KC by monoclonal
      antibodies reduced reperfusion-induced firm adhesion of leukocytes by 73% and
      75%, respectively. Interestingly, combined inhibition of MIP-2 and KC
      additionally decreased leukocyte rolling by 79%, but did not further reduce the
      number of firmly adherent leukocytes. To study the role of oxygen free radicals
      (OFRs) in the regulation of CXC chemokine expression, additional animals were
      pretreated with the xanthine-oxidase inhibitor allopurinol. In fact, allopurinol
      treatment reduced the colonic levels of MIP-2 and KC by 62% and 64%,
      respectively. This study elucidates important interactions between OFRs and
      chemokines in the I/R-induced leukocyte response in the mouse colon. Moreover,
      our data demonstrate that CXC chemokines play a fundamental role in colonic I/R
      and that functional interference with CXC chemokines may protect against
      pathological inflammation in the colon.

PMID- 14583343
TI  - Plasma nitrite reflects constitutive nitric oxide synthase activity in mammals.
AB  - Changes in plasma nitrite concentration in the human forearm circulation have
      recently been shown to reflect acute changes in endothelial nitric oxide synthase
      (eNOS)-activity. Whether basal plasma nitrite is a general marker of constitutive
      NOS-activity in vivo is yet unclear. Due to the rapid metabolism of nitrite in
      blood and the difficulties in its analytical determination literature data on
      levels of nitrite in mammals are largely inconsistent. We hypothesized that
      constitutive NOS-activity in the circulatory system is relatively uniform
      throughout the mammalian kingdom. If true, this should result in comparable
      systemic plasma nitrite levels in different species. Using three different
      analytical approaches we determined plasma nitrite concentration to be in a
      nanomolar range in a variety of species: humans (305 +/- 23 nmol/l), monkeys (367
      +/- 62 nmol/l), minipigs (319 +/- 24 nmol/l), dogs (305 +/- 50 nmol/l), rabbits
      (502 +/- 21 nmol/l), guinea pigs (412 +/- 44 nmol/l), rats (191 +/- 43 nmol/l),
      and mice (457 +/- 51 nmol/l). Application of different NOS-inhibitors in humans,
      minipigs, and dogs decreased NOS-activity and thereby increased vascular
      resistance. This was accompanied by a significant, up to 80%, decrease in plasma
      nitrite concentration. A comparison of plasma nitrite concentrations between
      eNOS(-/-) and NOS-inhibited wild-type mice revealed that 70 +/- 5% of plasma
      nitrite is derived from eNOS. These results provide evidence for a uniform
      constitutive vascular NOS-activity across mammalian species.

PMID- 14583344
TI  - Melatonin reduces glial reactivity in the hippocampus, cortex, and cerebellum of
      streptozotocin-induced diabetic rats.
AB  - Hyperglycemia plays a critical role in the development and progression of
      diabetic neuropathy. One of the mechanisms by which hyperglycemia causes neural
      degeneration is via the increased oxidative stress that accompanies diabetes.
      Metabolic and oxidative insults often cause rapid changes in glial cells. Key
      indicators of this response are increased synthesis of glial fibrillary acidic
      protein (GFAP) and S100B, both astrocytic markers. In the present study, we
      examined glial reactivity in hippocampus, cortex, and cerebellum of
      streptozotocin (STZ)-induced diabetic rats by determining the expression of GFAP
      and S-100B and we evaluated the effect of melatonin on the glial response.
      Western blot measurement of contents in brain regions after 6 weeks of STZ
      induced diabetes indicated significant increases in these constituents compared
      with those in nondiabetic controls. Administration of melatonin prevented the
      upregulation of GFAP in all brain regions of diabetic rats. Using GFAP
      immunohistochemistry, we observed an increase in GFAP immunostaining in the
      hippocampus of STZ-diabetic rats relative to levels in the control brains.
      Treatment with melatonin resulted in an obvious reduction of GFAP-immunoreactive
      astrocytes in hippocampus. Like GFAP, S100B levels also were increased in all
      three brain areas of diabetic rats, an effect also reduced by melatonin
      treatment. Finally, the levels of lipid peroxidation products were elevated as a
      consequence of diabetes, with this change also being prevented by melatonin.
      These results suggest that diabetes causes increased glial reactivity possibly
      due to elevated oxidative stress, and administration of melatonin represents an
      achievable adjunct therapy for preventing gliosis.

PMID- 14583345
TI  - Free radical scavenging efficiency of Nano-Se in vitro.
AB  - In this study, we showed that smaller size particles of Nano-Se have better
      scavenging effects on the following free radicals: carbon-centered free radicals
      (R*) generated from 2,2'-azo-bis-(2-amidinopropane) hydrochloride (AAPH), the
      relatively stable free radical 1,1-diphenyl-2-picryhydrazyl (DPPH), the
      superoxide anion (O2*-) generated from the xanthine/xanthine oxidase (X/XO)
      system, singlet oxygen (1O2) generated by irradiated hemoporphyrin. Furthermore,
      the three sizes of Nano-Se studied also show protective effects against the
      oxidation of DNA. The three samples all have potential size-dependent
      characteristics on scavenging the free radicals. Although in this study we
      regarded Nano-Se as a whole without considering interactions between BSA and the
      red selenium nano-particles, there is the possibility that the apparent free
      radical scavenging effects may be partially contributed by such interactions.

PMID- 14583347
TI  - Oxidative DNA damage (8-hydroxydeoxyguanosine) and body iron status: a study on
      2507 healthy people.
AB  - To clarify the relationship of oxidative stress and body iron status, we detected
      urinary 8-hydroxydeoxyguanosine (8-OHdG) as a biomarker of oxidative DNA damage,
      and measured serum ferritin and total iron-binding capacity (TIBC), both
      reflecting body iron store, on 2507 healthy people aged between 22 and 89 years
      (males, 1253; females, 1254). The urinary 8-OHdG excretion of males showed almost
      no change with age, but the excretion of premenopausal females was lower than
      that of males, whereas postmenopausal females excreted significantly more than
      males. The values of serum ferritin showed no remarkable change with age in
      males, but increased gradually in postmenopausal females without iron loss due to
      bleeding, although the males' values remained higher than those of females at all
      ages (p<.05). On the other hand, the values of TIBC remained within the narrow
      limits in males, regardless of age, whereas those of females always stayed at a
      higher level than the males (p<.05). Conclusively, urinary 8-OHdG correlated with
      serum ferritin positively and with TIBC inversely, which suggested that body iron
      status would control the generation of 8-OHdG in vivo. After all, the increase of
      urinary 8-OHdG excretion in postmenopausal females may be caused by the decrease
      of body iron loss.

PMID- 14583346
TI  - Peroxidation and externalization of phosphatidylserine associated with release of
      cytochrome c from mitochondria.
AB  - Production of reactive oxygen species (ROS) during apoptosis is associated with
      peroxidation of phospholipids particularly of phosphatidylserine (PS). The
      mechanism(s) underlying preferential PS oxidation are not well understood. We
      hypothesized that cytochrome c (cyt c) released from mitochondria into cytosol
      acts as a catalyst that utilizes ROS generated by disrupted mitochondrial
      electron transport for PS oxidation. Selectivity of PS oxidation is achieved via
      specific interactions of positively charged cyt c with negatively charged PS. To
      test the hypothesis we employed temporary transfection of Jurkat cells with a pro
      apoptotic peptide, DP1, a conjugate consisting of a protein transduction domain,
      PTD-5, and an antimicrobial domain, KLA [(KLAKLAK)2], known to selectively
      disrupt mitochondria. We report that treatment of Jurkat cells with DP1 yielded
      rapid and effective release of cyt c from mitochondria and its accumulation in
      cytosol accompanied by production of H2O2. Remarkably, this resulted in selective
      peroxidation of PS while more abundant phospholipids such as phosphatidylcholine
      (PC) and phosphatidylethanolamine (PE) remained nonoxidized. Neither PTD-5 alone
      nor KLA alone exerted any effect on PS peroxidation. Redox catalytic involvement
      of cyt c in PS oxidation was further supported by our data demonstrating that:
      (i) specific interactions of cyt c with PS resulted in the formation of EPR
      detectable protein-centered tyrosyl radicals of cyt c upon its interaction with
      H2O2 in the presence of PS-containing liposomes, and (ii) integration of cyt c
      into cytochrome c null (Cyt c -/-) cells or HL-60 cells specifically stimulates
      PS oxidation in the presence of H2O2 or t-BuOOH, respectively. We further
      demonstrated that DP1 elicited externalization of PS on the surface of Jurkat
      cells and enhanced their recognition and phagocytosis by J774A.1 macrophages. Our
      results are compatible with the hypothesis that catalysis of selective PS
      oxidation during apoptosis by cytosolic cyt c is important for PS-dependent
      signaling pathways such as PS externalization and recognition by macrophage
      receptors.

PMID- 14583348
TI  - Second order rate constants: a cautionary note.

PMID- 14583349
TI  - Usefulness of myocardial blush grade early and late after primary coronary
      angioplasty for acute myocardial infarction in predicting left ventricular
      function.
AB  - This study sought to analyze the evolution of myocardial perfusion during follow
      up after primary angioplasty for acute myocardial infarction (AMI) and relate it
      to final left ventricular (LV) function. In 101 patients with a first AMI,
      angiographic myocardial blush grade (MBG) was analyzed immediately after
      intervention and at follow-up 7.5 +/- 5.6 months later. Cine ventriculography was
      performed at follow-up angiography to define LV function. Five patients had
      occluded stents or flow-limiting restenosis. In the remaining patients,
      myocardial perfusion at follow-up, as defined by MBG, was persistently abnormal
      in 19 patients (20%), had become normalized from previously abnormal MBG in 30
      patients (31%), remained normal in 40 patients (42%), and deteriorated from
      normal to abnormal in 7 patients (7%). Patients with improvement of abnormal
      blush determined immediately after intervention to normal blush at follow-up (n =
      30) compared with patients with persistently abnormal blush (n = 19) had a better
      LV ejection fraction at follow-up (53.7 +/- 11.1 vs. 37.4 +/- 9.7%, p <0.001).
      Evolution of MBG had a better predictive value for LV ejection fraction at follow
      up than acute MBG only. Multivariate analysis proved evolution of MBG from AMI to
      follow-up to be an independent predictor of LV function (R(2) = 0.177, p <0.001)
      in addition to the initial size of jeopardized myocardium as defined by the sum
      of ST-segment elevation (R(2) = 0.138, p = 0.001) and infarct location (R(2) =
      0.044, p = 0.033). In conclusion, tissue reperfusion after angioplasty for AMI is
      characterized by frequent improvement over time, as indicated by repeated MBG
      analysis. Patients with recovery of perfusion have better, final LV function.

PMID- 14583350
TI  - Comparison of effectiveness of angiotensin-converting enzyme inhibitors after
      acute myocardial infarction in diabetic versus nondiabetic patients.
AB  - Mortality and morbidity after acute myocardial infarction (AMI) is higher in
      diabetic than in nondiabetic patients. Angiotensin-converting enzyme (ACE)
      inhibitors have been shown to exert a beneficial effect after AMI. We sought to
      evaluate the association between treatment with ACE inhibitors and 1-year outcome
      after AMI in diabetic and nondiabetic patients in a national survey. The study
      population was drawn from a national survey conducted in all coronary care units
      operating in Israel during a 5-month period in 1996, and included 2,179 patients
      with AMI: 533 diabetics (24%), 322 of whom received ACE inhibitors (60%) and 211
      who did not; and 1,646 nondiabetics, 805 of whom received ACE inhibitors and 841
      who did not. In both groups of patients, those treated with ACE inhibitors were
      older, included more women, more had a history of AMI, anterior wall AMI, or
      hypertension, and more had worse Killip class on admission. Diabetic patients
      treated with ACE inhibitors experienced lower 1-year mortality rates than
      diabetics not treated with ACE inhibitors (16.2% vs 18.8%, respectively;
      covariate adjusted hazard ratio 0.47, 95% confidence interval 0.30 to 0.74). In
      nondiabetic patients, however, ACE inhibitor treatment was not associated with a
      better outcome (10.2% vs 7.3%, respectively; covariate adjusted hazard ratio
      0.80; 95% confidence interval 0.56 to 1.15). Thus, treatment with ACE inhibitors
      after AMI appears to be particularly beneficial in diabetic patients. The
      beneficial effect observed supports the widespread use of ACE inhibitors in
      diabetic patients after AMI.

PMID- 14583351
TI  - Independent contribution of plaque complexity to myocardial ischemia during
      dobutamine stress echocardiography.
AB  - The influence of complex plaque morphology on the extent of demand-induced
      ischemia in unselected patients is not well defined. We sought to investigate the
      functional significance of lesion morphology in patients who underwent coronary
      angiography and dobutamine stress echocardiography (DSE). Angiography and DSE
      were performed within a 6-month period (mean 1 +/- 1 month) in 196 patients.
      Angiographic assessments involved quantification of stenosis severity, assessment
      of the extent of jeopardized myocardium, and categorization of plaque morphology
      according to the Ambrose classification. DSE was interpreted by separate
      investigators with respect to wall motion score index (WMSI) and number of
      coronary territories involved. A general linear model was constructed to assess
      the independent contribution of patient characteristics and angiographic and DSE
      results with respect to extent of ischemic myocardium. Complex lesion morphology
      was seen in 62 patients (32%). Patients with complex lesions were more likely to
      have had prior myocardial infarction (p <0.001) and be current smokers (p =
      0.03). During angiography, they exhibited a trend toward a greater number of
      diseased vessels, had a greater coronary jeopardy score (p <0.001) and more
      frequent collateral flow (p = 0.03). During echocardiography, patients had a
      higher stress WMSI (p <0.001) and were more likely to show ischemia in all 3
      arterial territories (p <0.01). On multivariate regression, the coronary artery
      jeopardy score and the presence of complex plaque morphology were independent
      predictors of the extent of ischemic myocardium (R(2) = 34%, p <0.001). Thus,
      patients with complex plaque morphology are older, more likely to smoke, and more
      likely to have had prior myocardial infarction. They exhibit more extensive
      disease with higher coronary jeopardy scores and a higher resting and peak stress
      WMSI. Despite these differences, complex plaque morphology remains an independent
      predictor of the extent of ischemia during stress.

PMID- 14583352
TI  - Comparison of outcomes of patients with acute coronary syndromes with and without
      atrial fibrillation.
AB  - Preexisting or new-onset atrial fibrillation (AF) commonly occurs in patients
      with an acute coronary syndrome (ACS). However, it is currently unknown if
      previous or new-onset AF confers different risks in these patients. To determine
      the prognostic significance of new-onset and previous AF in patients with ACS, we
      evaluated all patients with ACS enrolled in the multinational Global Registry of
      Acute Coronary Events (GRACE) between April 1999 and September 2001. We compared
      clinical characteristics, management, and hospital outcomes in patients with ACS
      and new-onset and previous AF with those without AF. Of a total of 21,785
      patients with ACS enrolled in GRACE, 1,700 (7.9%) had previous AF and 1,221
      (6.2%) had new-onset AF. Patients with any AF were older, more likely to be
      women, had more co-morbid conditions, and worse hemodynamic status. Most in
      hospital adverse events (reinfarction, shock, pulmonary edema, bleeding, stroke,
      and mortality) were significantly higher in patients with any AF than those
      without AF. Only new-onset AF (not previous AF) was an independent predictor of
      all adverse in-hospital outcomes. We conclude that compared with patients with
      ACS without any AF, previous and new-onset AF are associated with increased
      hospital morbidity and mortality. However, only new-onset AF is an independent
      predictor of in-hospital adverse events in patients with ACS.

PMID- 14583353
TI  - Effectiveness of rhythm control in persistent or permanent atrial fibrillation
      with overdrive atrial pacing and antiarrhythmic drugs after linear right atrial
      catheter ablation.
AB  - Right atrial (RA) maze procedures using linear catheter ablation have had limited
      efficacy in paroxysmal atrial fibrillation (AF). We hypothesized that "hybrid"
      therapy using overdrive atrial pacing and antiarrhythmic drugs can improve
      efficacy of catheter RA maze and expand its role to persistent or permanent AF.
      Catheter RA maze procedures were performed in 26 patients with persistent or
      permanent AF refractory to 4.5 +/- 2.1 antiarrhythmic drugs. Overdrive dual-site
      RA pacing (21 patients) or high RA pacing (5 patients) was continued (n = 11) or
      instituted periablation (n = 15). All patients continued receiving previously
      ineffective antiarrhythmic drugs. Freedom from permanent AF (rhythm control),
      symptomatic and/or asymptomatic AF recurrences, the safety of hybrid therapy, and
      overall survival were assessed. There was no procedure-related mortality or
      stroke. Rhythm control was achieved in 24 patients (92%) within 3 months. During
      long-term follow-up (6 to 49 months, mean 17 +/- 10), rhythm control was
      maintained in 20 patients (77%). Nine patients (35%) had no AF recurrences,
      whereas 11 patients maintained rhythm control with infrequent AF recurrences.
      Device datalogs at the study cut-off point demonstrated no AF events in 6
      patients, nonsustained atrial tachycardia in 2 patients, and brief asymptomatic
      paroxysmal AF in 12 patients. Actuarial patient survival was 95% at 1 year and
      74% at 2 years of follow-up. Thus, hybrid therapy utilizing catheter RA maze
      procedures with overdrive atrial pacing and antiarrhythmic drugs can be performed
      safely and can reestablish rhythm control in selected patients with refractory
      persistent or permanent AF.

PMID- 14583354
TI  - Frequency of recurrence among infants with supraventricular tachycardia and
      comparison of recurrence rates among those with and without preexcitation and
      among those with and without response to digoxin and/or propranolol therapy.
AB  - Approximately 60% of children with supraventricular tachycardia (SVT) develop
      their initial episode by 1 year of age. Despite resolution in most of these
      patients by 1 year, approximately 30% of the SVT will recur. We performed a
      retrospective review of all patients <1 year of age with SVT between January 1984
      and December 2000. Recurrence was defined as documented SVT at >1 year of age.
      Patients were divided into: (1) a first line (FL) group (controlled with digoxin
      and/or propranolol) and (2) a second line (SL) group (requiring additional
      antiarrhythmics). The groups were divided based on the presence of preexcitation.
      The FL group included 116 patients, 20 of whom (17%) had Wolff-Parkinson-White
      (WPW) syndrome. The SL group included 34 patients, 21 of whom (62%) had WPW (p
      <0.001). Recurrence of SVT occurred in 32 patients (28%) in the FL group and in
      23 patients (68%) in the SL group (p <0.001). SVT recurred in 36 of 41 patients
      (88%) with WPW compared with 19 of 109 patients (17%) without WPW syndrome (p
      <0.001). Logistic regression analysis demonstrated that the presence of WPW
      syndrome was associated with a 29-fold higher odds of SVT recurrence (p <0.001),
      and that patients with WPW syndrome were more likely to require additional
      antiarrhythmic therapy (p <0.001). Thus, patients with WPW syndrome who had SVT
      at <1 year of age have 29-fold higher odds of recurrence at >1 year of age versus
      those patients with preexcitation. These patients are also more likely to require
      additional antiarrhythmic therapy to control SVT. Furthermore, children with WPW
      syndrome who are refractory to treatment with digoxin and/or propranolol are at
      increased risk of SVT recurrence.

PMID- 14583355
TI  - Hemodynamic response to intensive unloading therapy (furosemide and
      nitroprusside) in patients >70 years of age with left ventricular systolic
      dysfunction and decompensated chronic heart failure.
AB  - In patients with decompensated chronic congestive heart failure (CHF), intensive
      unloading therapy allows an acute decrease in ventricular filling pressures and
      improves long-term prognosis. Because elderly patients do not routinely undergo
      invasive hemodynamic evaluation, they are generally denied such a pharmacologic
      approach. We prospectively characterized the acute hemodynamic response to
      intensive unloading and its prognostic significance in a elderly population with
      CHF who were hospitalized for cardiac decompensation. Fifty-nine patients aged
      >70 years with left ventricular systolic dysfunction underwent intensive
      unloading therapy (furosemide and nitroprusside) tailored to reduce ventricular
      filling pressures to near-normal levels. The hemodynamic parameters were
      monitored by Doppler echocardiography. At baseline, left and right ventricular
      filling pressures were 21 +/- 3 and 10 +/- 3 mm Hg, respectively. Although all
      patients experienced a relevant improvement in clinical status during hospital
      stay, a significant reduction of ventricular filling pressures was detected at
      discharge in only 40 of them (68%) (responders), whereas 19 patients (32%) had a
      deficient response to therapy (nonresponders). This unfavorable behavior was
      predicted by the presence of renal dysfunction at admission. During 19-month
      follow-up, death due to cardiovascular causes occurred in 8 of 40 responders
      (20%) and in 9 of 19 nonresponders (47%) (p <0.005). Hospitalizations for
      cardiovascular causes were more frequent in the nonresponders (58% vs 8%, p
      <0.0001). Thus, a deficient hemodynamic response to intensive unloading treatment
      is not infrequent in elderly patients with decompensated CHF. This behavior is
      predicted by renal dysfunction at admission and is associated with poorer
      outcome.

PMID- 14583356
TI  - Weights of operatively-excised stenotic unicuspid, bicuspid, and tricuspid aortic
      valves and their relation to age, sex, body mass index, and presence or absence
      of concomitant coronary artery bypass grafting.
AB  - This study was designed to evaluate weights of operatively-excised stenotic
      aortic valves and to compare them with age, sex, body mass index, and presence or
      absence of concomitant coronary artery bypass grafting. Weights of operatively
      excised stenotic aortic valves have not been previously reported. We weighed
      operatively-excised stenotic valves in 499 patients (aged 19 to 91 years, mean
      70), none of whom had mitral valve replacement. The 499 aortic valves ranged in
      weight from 0.45 to 11.30 g (mean 2.67). The mean weights of the unicuspid and
      bicuspid valves were heavier than those of the tricuspid valves (4.36 vs 3.34 vs
      2.04 g, p <0.05). Mean valve weights were greater in the 304 men than in the 195
      women (3.19 vs 1.87 g, p <0.001), in the younger patients than in the older
      patients (3.13 g in patients <or=40 years old vs 2.89 g in patients 41 to 70
      years old and 2.47 g in patients 71 to 91 years old, p <0.05), and in the 230
      patients who did not undergo simultaneous coronary artery bypass grafting
      compared with the 269 patients who had this additional procedure (2.94 vs 2.45 g,
      p <0.001). The mean weights of the valves were similar in patients whose body
      mass index was <25, 25 to 30, and >30 kg/m(2) (2.62 vs 2.76 vs 2.57 g). Weights
      of operatively-excised stenotic aortic valves provide objective evidence of
      valvular stenosis.

PMID- 14583358
TI  - Current status of clinical electrocardiography with suggestions for the
      improvement of the interpretive process.

PMID- 14583357
TI  - Usefulness of preoperative stress perfusion imaging in predicting prognosis after
      liver transplantation.
AB  - The role of preoperative stress single-photon emission computed tomographic
      (SPECT) imaging in patients with end-stage liver disease who underwent liver
      transplantation is not well established. We reviewed medical records of patients
      who had liver transplantation at our institution between January 1998 and
      November 2001. During this time, 339 patients (213 men, aged 51 +/- 11 years)
      underwent liver transplantation. Of these, 87 patients had preoperative stress
      SPECT imaging. Diabetes mellitus (30% vs 11%), hypertension (26% vs 12%), and
      coronary artery disease (15% vs 7%) were more prevalent in those with than
      without SPECT (p <0.01 each). The stress SPECT perfusion images were normal in 78
      patients (91%) and the left ventricular ejection fraction was 72 +/- 10%. SPECT
      images revealed ascites in 66% and splenomegaly in 83% of patients. There were 35
      total deaths (10%) and 5 nonfatal myocardial infarctions over a mean follow-up of
      21 +/- 13 months. Most deaths (32 of 35) were noncardiac and sepsis was the most
      common cause of death. A normal SPECT study had a 99% negative predictive value
      for perioperative cardiac events. Kaplan-Meier survival curves showed an 87% 2
      year cumulative survival rate in the total group. Thus, in patients undergoing
      liver transplantation, 2-year survival depends on early noncardiac events. A
      normal stress SPECT study identified patients at a very low risk for early and
      late cardiac events despite a higher risk profile. SPECT images also revealed
      unique findings, such as ascites and splenomegaly, which could produce image
      artifacts and may interfere with accurate image interpretation.

PMID- 14583359
TI  - Comparison of effectiveness and safety of three different antithrombotic regimens
      (bivalirudin, eptifibatide, and heparin) in preventing myocardial ischemia during
      percutaneous coronary intervention.
AB  - The aim of this retrospective, observational analysis was to compare the efficacy
      and safety of 3 antithrombotic regimens: bivalirudin, eptifibatide plus heparin,
      and heparin alone, with emphasis on preventing interventional procedural
      creatinine kinase-MB fraction (CK-MB) release, and consequently, myocardial
      necrosis.

PMID- 14583360
TI  - Comparison of effect of glycoprotein IIb/IIIa inhibitors during percutaneous
      coronary interventions on risk of hemorrhagic stroke in patients >or=75 years of
      age versus those <75 years of age.
AB  - Of 1,369 consecutive patients who underwent stent-assisted coronary angioplasty
      and who were treated with glycoprotein IIb/IIIa inhibitors during these
      procedures, 17.5% were >or=75 years of age. Compared with patients <75 years old,
      those >or=75 years of age had similar procedural and in-hospital outcomes but
      significantly higher rates of hemorrhagic stroke (0.08% vs 1.2%, p <0.001).

PMID- 14583361
TI  - Late (>or=6 years) results of combined coronary artery bypass grafting and mitral
      valve replacement for severe mitral regurgitation secondary to acute myocardial
      infarction.
AB  - Analysis of outcomes in 31 patients who had combined mitral valve replacement
      (MVR) and coronary artery bypass grafting (CABG) for ischemic mitral
      regurgitation (MR) disclosed that 12 patients had MR because of papillary muscle
      rupture and that 19 patients had MR because of papillary muscle necrosis or
      fibrosis without rupture. Of the 12 patients with rupture, 6 died within 2 months
      of operation and the other 6 lived >or=6 years postoperatively; of the 19
      patients without rupture, none died within 2 months of operation and 11 (58%)
      lived at least 6 years.

PMID- 14583362
TI  - Outcomes following bail-out abciximab administration during primary intervention
      in acute myocardial infarction (The CADILLAC Trial).
AB  - The utility of glycoprotein IIb/IIIa receptor inhibitors as a "bail-out" modality
      after unsuccessful primary percutaneous coronary intervention for acute
      myocardial infarction is unknown. In the CADILLAC trial, of 1,030 control
      patients, 62 patients (6.0%) crossed over and received abciximab for procedural
      complications or suboptimal angioplasty results. Compared with patients who
      received routine upfront abciximab, those treated with bail-out abciximab had
      markedly lower rates of Thrombolysis In Myocardial Infarction grade 3 flow and
      increased rates of hemorrhagic and ischemic complications at 30 days and 1 year.

PMID- 14583363
TI  - Outcomes of bail-out stenting for suboptimal balloon angioplasty during primary
      intervention in acute myocardial infarction (The CADILLAC trial).
AB  - The results of bail-out stenting after unsuccessful primary balloon angioplasty
      compared with routine stenting or successful balloon angioplasty in acute
      myocardial infarction are unknown. In the CADILLAC trial, 168 of 1,044 patients
      (16.1%) randomized to balloon angioplasty crossed over to stenting after
      unsuccessful dilatation. Event-free survival was similar after bail-out and
      routine stenting, and was greater than after successful balloon angioplasty.

PMID- 14583364
TI  - Combined effects of mild hypothermia and glycoprotein IIb/IIIa antagonists on
      platelet-platelet and leukocyte-platelet aggregation.
AB  - Endovascular cooling was assessed as a potential treatment for percutaneous
      coronary intervention in patients with acute myocardial infarction. Here we show
      that mild hypothermia: (1) inhibits platelet aggregation; (2) augments
      eptifibatide- and tirofiban- but not abciximab-induced inhibition of platelet
      aggregation; (3) increases the formation of adenosine diphosphate-induced
      leukocyte-platelet aggregates; and (4) diminishes the glycoprotein IIb/IIIa
      antagonist-induced decrease in leukocyte-platelet aggregates.

PMID- 14583365
TI  - Effect of apolipoprotein E alleles and angiotensin-converting enzyme
      insertion/deletion polymorphisms on lipid and lipoprotein markers in middle-aged
      men and in patients with stable angina pectoris or healed myocardial infarction.
AB  - The effects of the apolipoprotein E epsilon and angiotensin-converting enzyme
      insertion/deletion alleles on lipid levels and hypolipidemic drug treatment was
      assessed in 400 men with stable angina pectoris or healed myocardial infarction
      and 338 healthy controls. The data indicate that epsilon4 carriers have increased
      total and low-density lipoprotein cholesterol levels, that the epsilon4 allele
      unfavorably decreases the efficiency of statin treatment, and that the
      angiotensin-converting enzyme insertion/deletion polymorphism exerts no
      significant effect, with the exception of an increase in apolipoprotein E levels.

PMID- 14583367
TI  - Pharmacoeconomic evaluation of the effects of atorvastatin on early recurrent
      ischemic events in acute coronary syndromes.
AB  - An economic analysis was conducted using clinical outcomes in the MIRACL trial
      that evaluated high-dose atorvastatin versus placebo for 16 weeks after acute
      coronary syndrome. The direct cost of atorvastatin was largely offset by the
      associated decrease in cardiovascular events. The net incremental cost of
      atorvastatin treatment was 157 dollars/patient with a cost-effectiveness ratio of
      4,086 dollars/event avoided.

PMID- 14583366
TI  - Adherence with statin therapy in secondary prevention of coronary heart disease
      in veterans administration male population.
AB  - This retrospective cohort study enrolled 8,768 male Veterans Administration
      patients with coronary heart disease who were prescribed statins from July 1,
      1999, to June 30, 2000. After 18 months of follow-up, 71% of the patients had
      been dispensed >or=80% of the medication. Our population's persistence in using
      statins was higher than in other open-population cohorts but lower than in
      randomized controlled trials.

PMID- 14583368
TI  - Effect of pretreatment vitamin D levels on in vivo effects of atorvastatin on
      bone metabolism in patients with heterozygous familial hypercholesterolemia.
AB  - To find the clinical variables associated with atorvastatin's effects on bone
      metabolism markers, 35 patients with heterozygous familial hypercholesterolemia
      were treated with atorvastatin for 24 weeks, and the levels of bone formation
      markers (bone-specific alkaline phosphatase and osteocalcin) and resorption
      marker (urine collagen type-1 cross-linked N-telopeptide) were determined.
      Pretreatment vitamin D levels showed significant and positive associations with
      changes in 2 bone formation markers. The serial changes in 3 markers were
      favorable-increased bone formation markers and unchanged bone resorption marker
      but the changes occurred only in patients with pretreatment vitamin D levels >50
      pg/ml.

PMID- 14583370
TI  - Atropine-facilitated electrical cardioversion of persistent atrial fibrillation.
AB  - Conventional electrical cardioversion failed to restore normal sinus rhythm (NSR)
      in 49 of 364 patients (13.5%) with persistent atrial fibrillation. After
      receiving up to 2 mg of atropine, 40 (81%) of these 49 "electrical-refractory"
      patients were successfully cardioverted to NSR by subsequent attempts of
      electrical cardioversion.

PMID- 14583369
TI  - Comparison of effectiveness of carvedilol versus bisoprolol for maintenance of
      sinus rhythm after cardioversion of persistent atrial fibrillation.
AB  - Ninety patients who underwent cardioversion of persistent atrial fibrillation
      (AF) were randomized to bisoprolol 5 to 10 mg once daily or carvedilol 12.5 to 25
      mg twice daily. Using intention-to-treat analysis, 23 patients (46%) in the
      bisoprolol group and 17 patients (32%) in the carvedilol group relapsed into AF
      during the 1 year of total follow-up (p = 0.486). Patients treated with
      carvedilol had a 14% (hazard ratio 0.86) lower risk of relapse of AF compared
      with patients in the bisoprolol group, although results were statistically
      insignificant (p = 0.661) after controlling for patient age, gender, baseline
      heart rate, and left atrial diameter.

PMID- 14583371
TI  - Recurrence rate of atrial flutter after initial presentation in patients on drug
      treatment.
AB  - Atrial flutter (AFl) recurrence after initial in-patient presentation,
      cardioversion, and drug treatment is almost universal, often leading to
      rehospitalization and risk of serious clinical consequences. Radiofrequency
      ablation of AFl, which has an excellent safety record, should be evaluated as a
      first-line approach for most patients with AFl.

PMID- 14583372
TI  - Brain natriuretic peptide is elevated in outpatients with atrial fibrillation.
AB  - Brain natriuretic peptide (BNP) levels were measured in 72 outpatients with
      chronic atrial fibrillation (AF) and in 49 control patients without AF. BNP
      levels were significantly higher in patients with AF (median value 131 pg/ml)
      than without AF (median value 49 pg/ml; p <0.001), and remained significantly
      higher after controlling for demographic and clinical variables.

PMID- 14583373
TI  - Usefulness of implantable loop recorders in office-based practice for evaluation
      of syncope in patients with and without structural heart disease.
AB  - Early use of an implantable loop recorder for evaluating unexplained syncope in
      an office-based electrophysiology practice is an effective approach in patients
      with and without structural heart disease. Documentation of rhythm with an
      implantable loop recorder at the time of symptoms is possible in approximately
      50% and 80% of patients in both groups after 1 and 2 years of follow-up,
      respectively.

PMID- 14583374
TI  - Effect of aortic valve replacement on c-reactive protein in nonrheumatic aortic
      stenosis.
AB  - Plasma levels of C-reactive protein were higher in 20 patients with bicuspid or
      trileaflet degenerative aortic stenosis than in 31 normal controls and in 19
      patients with pure aortic regurgitation. C-reactive protein decreased from before
      to 6 months after aortic valve replacement for aortic stenosis. These
      observations suggest that aortic stenosis is an inflammatory disease.

PMID- 14583375
TI  - Usefulness of transthoracic echocardiography for identification of left atrial
      thrombus before balloon mitral valvuloplasty.
AB  - The objectives of this study were (1) to identify clinical and transthoracic
      echocardiographic features of patients with mitral stenosis who have thrombus
      recognized on transesophageal echocardiography, and (2) to define a clinical and
      echocardiographic model to predict the presence of left atrial thrombus in these
      patients.

PMID- 14583376
TI  - Effectiveness of elective stenting of common carotid artery lesions in preventing
      stroke.
AB  - We report our experience with elective stenting of lesions only involving the
      origin and proximal common carotid arteries. In 37 patients (42 vessels),
      procedural success was 95% (40 of 42 vessels) with 2 minor strokes (4.70%) and no
      major strokes. Follow-up for a mean of 24 months showed 1 transient ischemic
      attack, 2 contralateral minor strokes, 1 cerebral hemorrhage associated with long
      term warfarin therapy, and a 5.1% restenosis rate. This technique is an excellent
      alternative for treating proximal and ostial lesions of the common carotid
      artery.

PMID- 14583378
TI  - Krakatoa--the ultimate heart attack.

PMID- 14583377
TI  - Validation of heart and lung teleauscultation on an Internet-based system.
AB  - The feasibility and accuracy of an Internet-based system for teleauscultation was
      evaluated in 103 cardiac patients, who were auscultated by the same cardiologist
      with a conventional stethoscope and with an Internet-based method, using an
      electronic stethoscope and transmitting heart and lung sounds between computer
      work stations. In 92% of patients, the results of electronic and acoustic
      auscultation coincided, indicating that teleauscultation may be considered a
      reliable method for assessing cardiac patients and could, therefore, be adopted
      in the context of comprehensive telecare programs.

PMID- 14583379
TI  - Left ventricular dilatation in normotensive, extremely overweight Japanese
      professional Sumo wrestlers.

PMID- 14583380
TI  - Spontaneous reports cannot serve as a basis for comparison of two drugs.

PMID- 14583381
TI  - Role of tachykinin NK1, NK2 and NK3 receptors in the modulation of visceral
      hypersensitivity in the rat.
AB  - Tachykinins are known to be involved in the processing of information leading to
      central sensitization and nociception. Using an animal model of repetitive
      colorectal distensions (CRD), we investigated the effect of spinal administration
      of tachykinin receptor antagonists in the mediation of visceral hypersensitivity.
      Intrathecal administration of the NK(1) receptor antagonist RP-67,580 (6.5 nmol)
      and the NK(3) receptor antagonist R-820 (6.5 nmol) completely blocked the CRD
      induced hyperalgesia for both noxious and innocuous stimuli. The intrathecal
      administration of SR-48,968, a tachykinin NK(2) receptor antagonist, did not
      affect the visceral pain threshold of hypersensitive animals. Thus, the results
      from the present experiment support the concept that tachykinins with actions at
      spinal NK(1) and NK(3) but not NK(2) receptor sites are involved in visceral
      hypersensitivity mediated by nociceptive and non-nociceptive afferent inputs.

PMID- 14583382
TI  - Trigeminal primary afferent projections to the peribrachial area in the guinea
      pig.
AB  - Transganglionic transport of horseradish peroxidase (HRP) was used to investigate
      trigeminal primary afferent endings in the peribrachial area of the guinea pig.
      After HRP application to several nerve branches of the three divisions of the
      trigeminal nerve, a projection to the caudal region of the ipsilateral
      peribrachial region was found for the infratrochlear, ethmoidal, supraorbital,
      zygomatic, zygomaticofacial, zygomaticotemporal and infraorbital-superior
      alveolar nerves. Random and scarce endings were also observed for the mental,
      inferior alveolar, buccal and mylohyoid nerves. No trigeminal primary projection
      to the peribrachial area was detected when HRP was applied to the sphenopalatine,
      lingual and auriculotemporal nerves. With the exception of the ethmoidal endings
      described in the muskrat, a primary afferent projection to the peribrachial
      region from the other trigeminal nerves has not hitherto been reported in
      mammals.

PMID- 14583383
TI  - Body equilibrium at the end of gait initiation: importance of ankle muscular
      force as evidenced in clubfoot children.
AB  - This study investigates the importance of ankle muscular force and foot shape on
      body equilibrium at the end of a first step by means of a comparison between
      healthy children and children with unilateral clubfoot who showed Triceps surae
      atrophy. Subjects were asked to initiate gait at different velocities and to
      perform a few forward-oriented steps. In healthy children, there was a
      significant increase in the number of positive values of the centre of gravity
      vertical acceleration at foot contact (Z"HC) as velocity increased without any
      difference between the preferred and non-preferred stepping foot. These results
      indicated that ankle muscular forces from the leg of support intervene in braking
      the downfall of the body, as velocity and step length increase, and that this
      function does not depend on the subject's lateralization. In comparison with
      healthy children, clubfoot subjects showed a greater occurrence of low or
      negative Z"HC values when gait was initiated at a velocity greater than 0.8 m/s.
      However, except for two of them, there was no difference in Z"HC control between
      the steps initiated with the sound leg and those initiated with the affected leg.
      These results indicate that in unilateral clubfoot children, residual
      musculoskeletal impairment of one leg induces a deficit in equilibrium control as
      soon as step length needs a significant braking of the body's vertical fall. It
      is also shown that equilibrium is not limited to the gait period where the
      affected leg is the body's supporting leg but also when it is the stepping one.
      This could reflect a global alteration of the body scheme preserving symmetry in
      the control of both legs.

PMID- 14583384
TI  - Rat oligodendroglial cell lines express a functional receptor for the chemokine
      CCL3 (macrophage inflammatory protein-1alpha).
AB  - Regulation of migration, proliferation and differentiation of oligodendrocyte
      precursor cells is central for the accurate assembly of myelin in the CNS. The
      recent demonstration that oligodendrocyte precursors express chemokine receptors
      suggests that chemokines are candidates to play a role in the regulation of
      migration, since they are important molecules involved in the trafficking of
      other cell types. Since the chemokine CCL3 (macrophage inflammatory protein
      1alpha) is expressed in various CNS diseases, we have used the oligodendrocyte
      precursor cell lines CG4 and OLN-93 to study the expression of receptors for CCL3
      and the influence of CCL3 on oligodendrocyte precursor behaviour.
      Oligodendroglial cells express the receptor CCR1, but not CCR5. CCL3 induced an
      intracellular rise in Ca(2+), a typical signalling event of G protein-coupled
      receptors. Migration of cells was slightly inhibited by CCL3, while proliferation
      was not affected. The implications on CNS development, during which expression of
      chemokines and their receptors occurs, and on inflammatory demyelinating diseases
      of the CNS, like multiple sclerosis, are discussed.

PMID- 14583385
TI  - NACP-REP1 polymorphism is not involved in Parkinson's disease: a case-control
      study in a population sample from southern Italy.
AB  - Contradictory evidence has been reported on the role of the polymorphic mixed
      dinucleotide repeat (NACP-REP1) of the alpha-synuclein gene as a risk factor for
      sporadic Parkinson's disease (PD). In the present study we genotyped the NACP
      REP1 polymorphism in 189 PD patients from southern Italy and 182 healthy control
      subjects. We failed to demonstrate an association of any NACP-REP1 allele with
      PD.

PMID- 14583386
TI  - Vagus nerve stimulation attenuates heat- and formalin-induced pain in rats.
AB  - The analgesic effect of vagus nerve stimulation (VNS) has not yet been
      demonstrated in animals with the devices used in the clinic. We studied in awake
      rats the effects of two VNS protocols on the hind paw hot water test and compared
      the results with those previously obtained in the oro-facial formalin test. A
      stringent duty cycle (20 s on/18 s off) increased heat pain tolerance in both
      hind paws (average 188%) after 2 h of stimulation. VNS with parameters used in
      epilepsy (30 s on/5 min off) decreased heat tolerance after 2 h, but produced a
      significant antinociceptive effect after days of stimulation. VNS may thus be
      useful in pain disorders, even with the less stringent protocol.

PMID- 14583387
TI  - Resveratrol promotes differentiation and induces Fas-independent apoptosis of
      human medulloblastoma cells.
AB  - Resveratrol has tumor-suppressive activities in some in vitro and in vivo
      experimental systems but its effect on medulloblastoma cells is still unknown. In
      this study, resveratrol was used to treat four human medulloblastoma cell lines
      (Med-3, UW228-1, -2 and -3) and its effects on cell growth, differentiation and
      death were examined by multiple approaches. Expression of Fas, FasL and caspase-3
      in the cells without and with resveratrol treatments was examined by
      immunocytochemical staining and mRNA in situ hybridization and the influence of
      anti-Fas antibody (200 ng/ml) in cell growth and survival was determined as well.
      The results demonstrated that resveratrol could suppress growth, promote
      differentiation and commit its target cells to apoptosis in time- and dose
      related fashions. Fas was constitutively expressed but FasL was undetectable in
      the four lines in spite of resveratrol treatment. Anti-Fas antibody (200 ng/ml)
      neither inhibited growth nor induced apoptosis of those cell lines. Up-regulated
      caspase-3 was found in resveratrol-treated populations and appearance of its
      cleaved form was closely associated with the apoptotic event. These findings
      suggest for the first time that resveratrol is an effective anti-medulloblastoma
      agent that kills medulloblastoma cells through a Fas-independent pathway.

PMID- 14583388
TI  - Thalamocortical cells in the cat pulvinar nucleus transiently express nitric
      oxide synthase during development.
AB  - We examined the postnatal expression of the neuronal form of nitric oxide
      synthase (nNOS) within the pulvinar and lateral posterior (LP) nuclei of the cat
      thalamus using immunocytochemical techniques. During the first postnatal month,
      nNOS was expressed in many cells within the pulvinar nucleus and medial
      subdivision of the LP nucleus; fewer neurons in the lateral LP nucleus were
      stained by the nNOS antibody. We examined the pulvinar nucleus to determine what
      cell types express nNOS. A comparison of the soma sizes of nNOS-stained cells to
      the overall population of Nissl-stained cells and interneurons (stained with an
      antibody against glutamic acid decarboxylase) suggests that within the pulvinar
      nucleus, thalamocortical cells express nNOS during development. In addition, the
      nNOS antibody stained axon bundles that traverse the pulvinar nucleus to enter
      the optic radiations, suggesting that thalamocortical cell axons also contain
      nNOS during development. However, this staining pattern was dramatically reduced
      by postnatal day 42 and later ages; the size of the remaining nNOS-stained cells
      was closer to that of interneurons, a subset of which contain nNOS in the adult
      pulvinar nucleus. This contrasts with our previous findings that nNOS is
      specifically expressed within interneurons in the developing dorsal lateral
      geniculate nucleus (LGN) and serves as further confirmation that the pulvinar
      nucleus and LGN represent distinct categories of thalamic nuclei.

PMID- 14583389
TI  - Neonatal depletion of serotonin increases the numbers of callosally projecting
      neurons in cat visual areas 17 and 18.
AB  - We investigated the influence of neonatal depletion of serotonin on the
      developmental reduction of callosal connections in cat visual cortex. Neonatal
      kittens were injected with 5,7-dihydroxytryptamine. At the age of 3 months, Fast
      Blue was injected into visual areas of one hemisphere in these and control cats
      and retrogradely labeled perikarya were mapped in the opposite hemisphere. In
      both groups callosally projecting neurons were found in a 3-5 mm wide belt
      centered on the transient zone of areas 17 and 18. However, numbers of labeled
      neurons were twice higher in the serotonin-depleted cats. We postulate that
      normally serotonin intensifies the process of axon pruning by augmenting
      developmental plasticity, therefore its depletion reduced the plasticity and more
      axons targeting callosal zones were stabilized, even though ectopic projections
      were still eliminated.

PMID- 14583391
TI  - The influence of handedness and gender on the microstructure of the human corpus
      callosum: a diffusion-tensor magnetic resonance imaging study.
AB  - The aim of the present study was to examine whether handedness and gender are
      associated with microstructural differences in human corpus callosum (CC). For
      this purpose, diffusion-tensor magnetic resonance imaging (DTI) was performed on
      34 right- and 33 left-handed subjects of both sexes. Four quantitative variables
      (Mean Diffusion, Relative Anisotropy, parallel and orthogonal diffusion) were
      computed within the CC. A significantly increased anisotropy was found in left-
      as compared to right-handed subjects, and in men as compared to women.
      Additionally, both overall and orthogonal diffusion were significantly lower in
      left- than in right-handed subjects. Possible interpretations of these findings
      are discussed. The novel DTI technique promises to further advance current
      understanding of morphological structure in the living brain.

PMID- 14583390
TI  - Effects of acetylcholine antagonist injection into the prefrontal cortex on the
      progress of lever-press extinction in rats.
AB  - To determine the relationship between cholinergic modulation within the rat
      medial prefrontal cortex (mPFC) and the progress of lever-press extinction, we
      conducted an experiment in which muscarinic and nicotinic acetylcholine (ACh)
      receptor antagonists were microinjected into the mPFC. The muscarinic antagonist
      injected immediately before the initial extinction training did not affect the
      progress of extinction during the training (no within-session effect), but
      disrupted a second re-training session the next day (across-session effect). By
      contrast, the nicotinic antagonist disrupted the progress of extinction both
      within and across training sessions. These results confirm that ACh in the mPFC
      modulates lever-press extinction and suggest that nicotinic and muscarinic
      receptors are involved in short- and long-term memory processes.

PMID- 14583392
TI  - Prefrontal theta oscillations associated with hand movements triggered by warning
      and imperative stimuli in the monkey.
AB  - In order to investigate the functional significance of theta oscillations in the
      brain, we recorded the cortical field potential in monkeys engaged in a visually
      initiated hand movement task. In each trial a warning signal (S1) was followed 3
      s later by an imperative signal (S2) to which the monkey had to respond to get a
      reward. The theta power in the prefrontal area 9 and the prelimbic area 32 was
      higher in the S1-S2 interval than in the pre-S1 period. This theta activity may
      be related to attentional processes and is probably a homologue of the human
      frontal midline theta (Fm theta) rhythms.

PMID- 14583393
TI  - Gonadotropin-releasing hormones modulate electrical activity of vasotocin and
      isotocin neurons in the brain of rainbow trout.
AB  - Gonadotropin-releasing hormone (GnRH) is widely distributed in the vertebrate
      brains; however, its significance in the brain function is poorly understood.
      Both GnRH and vasopressin-family hormones are involved in control of reproductive
      behavior. Anatomical evidence indicated the possible action of GnRH on classical
      neurosecretory neurons. In the present study, we examined whether GnRH modulates
      electrical activity of vasotocin (VT) and isotocin (IT) neurons in the brain of
      rainbow trout (Oncorhynchus mykiss). Two forms of GnRH, salmon GnRH and chicken
      GnRH II, are present in the rainbow trout brain, and their fibers are localized
      in the close vicinity of VT and IT neurons. Applications of both GnRH forms
      elevated the frequency of cell-type-specific synchronous Ca(2+) pulses in VT and
      IT neurons that are blocked by a GnRH-receptor antagonist. Our results showed
      facilitatory actions of GnRHs on VT and IT neurons, suggesting that GnRH neurons
      modulate classical neurosecretory neurons to control reproductive behavior.

PMID- 14583394
TI  - Serum brain-derived neurotrophic factor (BDNF) levels in schizophrenia are
      indistinguishable from controls.
AB  - Our previous study showed that serum brain-derived neurotrophic factor (BDNF) was
      significantly decreased in the antidepressant-naive patients with major
      depressive disorders. However, it was still unclear whether serum BDNF level was
      altered in drug-naive patients with schizophrenia. Using ELISA, we measured serum
      BDNF levels in antipsychotic-naive (n=15) and medicated (n=25) patients with
      schizophrenia, and in age- and sex-matched normal controls (n=40). There were no
      significant differences in serum BDNF levels among antipsychotic-naive (n=15) and
      medicated (n=25) patients and normal controls (n=40). Possible factors such as
      duration of illness, age of onset, Brief Psychiatric Rating Scale scores, and
      chlorpromazine equivalent dosages of antipsychotics did not reveal any
      significant correlations with BDNF levels. Our results do not support the view
      that serum BDNF levels are associated with schizophrenia.

PMID- 14583395
TI  - Orexin-immunoreactive inputs to rat sympathetic preganglionic neurons.
AB  - Orexin increases blood pressure and orexin-immunoreactive (IR) axons robustly
      innervate the spinal cord. Seeking anatomical evidence for direct effects of
      orexin on sympathetic preganglionic neurons (SPN), we used immunohistochemistry
      to study the relationships between orexin-IR axons and SPN identified by
      immunoreactivity for choline acetyltransferase (ChAT) or for cholera toxin B
      retrogradely transported from the superior cervical ganglion (SCG). In the
      intermediolateral cell column (IML), varicose, orexin-positive axons closely
      apposed almost all SPN in segments T1 and T2, but appositions were rare in T4-L2.
      Orexin fibers also apposed ChAT-IR cell bodies in the intercalated nucleus and
      the central autonomic area from T1 to L2. Orexin-IR synapses were identified
      ultrastructurally on SPN projecting to the SCG. Since SPN involved in
      cardiovascular control cluster in the IML of mid- and lower thoracic cord, these
      findings suggest that orexin affects blood pressure by acting on supraspinal
      neurons rather than SPN.

PMID- 14583396
TI  - Transduction of neurons lining the cerebral external capsules in mice with feline
      immunodeficiency virus based vectors.
AB  - Gene therapy in the brain has focused mainly on neurons (gray matter), with
      little comparable research on white matter. In this study, injections into mice
      cerebral white matter of mice were done to assess the distribution of gene
      transfer with recombinant feline immunodeficiency virus vectors expressing either
      beta-galactosidase or beta-glucuronidase. Our results show that vectors were
      preferentially distributed along the white matter of the external capsule, which
      was the site of vector injection as confirmed by horseradish peroxidase labeling.
      Moreover, we found gene transfer almost exclusively to NeuN(+) cells lining the
      external capsule, which then robustly secreted recombinant beta-glucuronidase
      throughout the white matter of the entire external capsule on the injected side.
      These results may have application to lysosomal storage diseases with widespread
      central nervous system deficits, and other disorders such as multiple sclerosis
      and human immunodeficiency virus dementia.

PMID- 14583397
TI  - Mutation analysis of the neurofilament M gene in Parkinson's disease.
AB  - Neurofilament M, a major component of Lewy bodies, represents an interesting
      candidate in the pathogenesis of Parkinson's disease (PD). We performed detailed
      mutation analyses of the NF-M gene in 322 familial and sporadic PD patients. Two
      polymorphisms (Ala475Thr and Gly697Arg) occurred at similar frequencies in PD
      patients and controls. A Pro725Gln substitution and a deletion of valine in
      position 829 were identified in two PD patients. These substitutions affect
      residues of the NF-M protein that are highly conserved among different species.
      None of our patients carried the Gly336Ser substitution, which has been described
      in familial PD. Our results argue against a major role of NF-M in PD. However,
      rare variants of the NF-M gene may act as susceptibility factors for PD and
      functional analyses of the identified variations are warranted to decipher
      possible mechanisms in neurodegeneration.

PMID- 14583398
TI  - Control of orientation of rat Schwann cells using an 8-T static magnetic field.
AB  - Schwann cells aid in neuronal regeneration in the peripheral nervous system via
      guiding the regrowth of axons. In this study, we investigated the magnetic
      orientation of Schwann cells, and of a mixture of Schwann cells and collagen,
      after an 8-tesla magnetic field exposure. We obtained cultured Schwann cells from
      dissected sciatic nerves of neonatal rats. After 60 h of magnetic field exposure,
      Schwann cells oriented parallel to the magnetic fields. In contrast, the mixture
      of Schwann cells and collagen, Schwann cells oriented in the direction
      perpendicular to the magnetic field after 2 h of magnetic field exposure. In this
      case, Schwann cells aligned along the collagen fiber oriented by magnetic fields.
      The magnetic control of Schwann cell alignment is useful in medical engineering
      applications such as nerve regeneration.

PMID- 14583399
TI  - Magnetic resonance image-guided implantation of chronic recording electrodes in
      the macaque intraparietal sulcus.
AB  - The implantation of chronic recording electrodes in the brain has been shown to
      be a valuable method for simultaneously recording from many neurons. However,
      precise placement of these electrodes, crucial for successful recording, is
      challenging if the target area is not on the brain surface. Here we present a
      stereotaxic implantation procedure to chronically implant bundles of recording
      electrodes into macaque cortical sulci, employing magnetic resonance (MR) imaging
      to determine stereotaxic coordinates of target location and sulcus orientation.
      Using this method in four animals, we recorded simultaneously the spiking
      activity and the local field potential from the parietal reach region (PRR),
      located in the medial bank of the intraparietal sulcus (IPS), while the animal
      performed a reach movement task. Fifty percent of all electrodes recorded spiking
      activity during the first 2 post-operative months, indicating their placement
      within cortical gray matter. Chronic neural activity was similar to standard
      single electrode recordings in PRR, as reported previously. These results
      indicate that this MR image-guided implantation technique can provide sufficient
      placement accuracy in cortical sulci and subcortical structures. Moreover, this
      technique may be useful for future cortical prosthesis applications in humans
      that require implants within sulci.

PMID- 14583400
TI  - Generating high gray-level resolution monochrome displays with conventional
      computer graphics cards and color monitors.
AB  - Display systems based on conventional computer graphics cards are capable of
      generating images with about 8-bit luminance resolution. However, most vision
      experiments require more than 12 bits of luminance resolution. Pelli and Zhang
      [Spatial Vis. 10 (1997) 443] described a video attenuator for generating high
      luminance resolution displays on a monochrome monitor, or for driving just the
      green gun of a color monitor. Here we show how to achieve a white display by
      adding video amplifiers to duplicate the monochrome signal to drive all three
      guns of any color monitor. Because of the lack of the availability of high
      quality monochrome monitors, our method provides an inexpensive way to achieve
      high-resolution monochromatic displays using conventional, easy-to-get equipment.
      We describe the design principles, test results, and a few additional
      functionalities.

PMID- 14583401
TI  - LTP in cultured hippocampal-entorhinal cortex slices from young adult (P25-30)
      rats.
AB  - Cultured hippocampal neurons and immature organotypic slice cultures overcome
      temporal limitations of acute hippocampal slices and have been useful for
      investigating long-lasting plasticity. Difficulties with culturing adult neurons
      have restricted such studies to preparations from embryonic, perinatal, and
      juvenile tissue. By improving the methods for culturing and maintaining
      hippocampal-entorhinal cortex slices obtained from mature rats (P25-30), we show
      that their use in long-term electrophysiological investigations is feasible. Our
      cultured slices maintained an intact and functional trisynaptic cascade, normal
      synaptic function, and reliable long-term recording stability for at least 14
      days in vitro. The electrophysiological properties and, in particular, the
      induction of long-term potentiation (LTP) in our mature organotypic slices were
      highly sensitive to dissection and tissue culture techniques. We present data
      describing the extracellular stimulation requirements for LTP-induction and its
      long-lasting maintenance (>4 h) at the Schaffer-collateral-CA1 synapse, and show
      that such changes in synaptic efficiency are NMDA receptor dependent. Our
      hippocampal-entorhinal cortex cultures from mature tissue can retain the
      electrophysiological properties required for long-term plasticity for several
      weeks in vitro.

PMID- 14583402
TI  - Automatic recognition of explorative strategies in the Morris water maze.
AB  - Notwithstanding the development of reliable tracking systems, the quantification
      methodology of the Morris water maze (MWM) has witnessed an operational mismatch
      between the indexes used to quantify MWM performance and the cognitive concepts
      derived from these indexes. Indeed, escape latency is the main, and often unique,
      performance measure used for the quantification of behavior. Aim of the present
      work was to overcome this limitation by presenting a methodology that allows for
      automatic categorical pattern recognition of the behavioral strategies performed
      in the MWM. By selecting few a priori and user-defined behavioral categories,
      many quantitative variables and regions of interest (ROIs), we used discriminant
      analysis (DA) to obtain 97.9% of correct automatic recognition of categories. The
      developed discriminant model (DM) also allowed to predict category membership of
      newly recorded swim paths with the same statistical efficacy (96%), and to
      identify the variables that better discriminate between adjacent categories. The
      combination of DA with a tracking system, a selection of many variables,
      different ROIs and qualitative categorization, reduces the gap between the
      measurement process and the categories used to describe a given behavior, and
      offers a methodology to computationally reproduce the human categorization of
      behaviors in the MWM.

PMID- 14583403
TI  - Functional magnetic resonance imaging in the awake rabbit: a system for stimulus
      presentation and response detection during eyeblink conditioning.
AB  - We describe a reliable system to control the timing of multiple stimuli and to
      detect eyeblink responses during functional magnetic resonance imaging (fMRI).
      The methods for stimulus delivery and timing, eyeblink detection, and response
      quantification are described in detail. We are using these methods in awake
      rabbits to study eyeblink conditioning (EBC) as a model paradigm for the study of
      learning and memory. Examples of conditioned eyeblinks in the awake rabbit during
      fMRI are presented for validation of our techniques. The results indicate that
      eyeblinks can be reliably recorded during fMRI, and that neither the stimulus
      delivery nor the response detection interferes with each other or affect the
      quality of the images. The combined fMRI/behavioral techniques should be useful
      for examining the entire brain simultaneously during the associative learning of
      a conditioned reflex in an animal model system.

PMID- 14583404
TI  - A simple method for isolation and characterization of mouse brain microvascular
      endothelial cells.
AB  - Brain endothelial cells, a site of the blood-brain barrier in vivo, regulate a
      number of physiological and pathophysiological processes in the brain including
      transport of nutrients, export of critical toxins, transmigration of circulating
      leukocytes and formation of new blood vessels. In this report, we describe a
      simple and reproducible method to isolate pure (>99%), functionally active
      endothelial cells from small quantities of adult mouse brain tissue. In vitro,
      these cells express typical phenotypic markers of differentiated brain
      endothelium such as von Willebrand factor, multiple drug resistant protein and
      glucose transporter-1, demonstrate uptake of acetylated low-density lipoprotein,
      and possess morphological and ultrastructural characteristics of microvascular
      endothelium. They form tight junctions and capillary-like tubes when stimulated
      by growth factors in an in vitro angiogenesis assay. In response to tumor
      necrosis factor-alpha, isolated mouse brain endothelial cells (MBEC) express
      vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1
      (ICAM-1). The protocol described here provides an effective and reliable method
      to isolate pure cerebral endothelium from adult mouse brain that should offer a
      useful tool for studying the role of altered vascular biology in mice with
      genetically manipulated brain disorders.

PMID- 14583405
TI  - Rapid and efficient electroporation-based gene transfer into primary dissociated
      neurons.
AB  - Non-viral gene transfer into neurons has proved to be a formidable task. Here, we
      describe an electroporation-based method that allows efficient and reliable DNA
      transfer into dissociated neural cells before they are plated and cultured. In
      hippocampal neural cells derived from either neonatal mouse or embryonic chicken
      brains, a high transfection rate was already observed 5 h after transfection, and
      reached 40-80% in 24 h, as monitored by expression of enhanced green fluorescent
      protein (eGFP). The level of eGFP expression per cell depended on the amount of
      DNA used in a gene transfer experiment. The survival and neuritic length of
      transfected cells resembled that of non-electroporated cells. The transfected
      neurons showed normal immunostaining for endogenous synaptic protein
      synaptophysin and the neural cell adhesion molecule (NCAM). Furthermore,
      efficient gene transfer of the NCAM isoform NCAM140 and eGFP-tagged NCAM140 could
      be achieved, allowing visualization of NCAM140 expression. Also, a
      glycosylphosphatidylinositol-anchored eGFP could be efficiently expressed,
      highlighting lipid rafts without altering electrophysiological properties of
      transfected neurons. When neurons transfected with green and red fluorescent
      proteins were cocultured, fine details of their interactions could be revealed in
      time-lapse experiments. Thus, the method provides a useful tool for elucidation
      of genes involved in different neuronal functions, including neurite outgrowth,
      synaptogenesis and synaptic transmission.

PMID- 14583406
TI  - A control system approach for evaluating somatosensory activation by laser
      Doppler flowmetry in the rat cortex.
AB  - Coupling between functional cortical activity and blood flow is a regulatory
      principle that adjusts the supply of substrates to the metabolic needs of the
      tissue. The flow response is usually expressed as the maximum increase over
      baseline; control system analysis allows the description of the entire time
      course and the main dynamic features of the regulative principle. In chloralose
      anesthetized rats, forepaws were stimulated by trains of electric pulses of 0.3
      or 5 ms duration. Blood flow was recorded in the contralateral somatosensory
      cortex by laser-Doppler flowmetry and correlated with the amplitude of primary
      somatosensory evoked potentials (SEP). Changes were analyzed by a control system
      approach. Pulses of 0.3 or 5 ms evoked SEPs of similar amplitude, whereas flow
      responses differed: 0.3 ms pulses led to a peak and plateau characteristic, 5 ms
      pulses evoked a plateau characteristic. The flow response evoked by 0.3 ms pulses
      can be modeled mathematically by an initial feedforward regulative principle
      followed after some delay by feedback controlled flow stabilization, whereas 5 ms
      pulses lack the feedforward component. The absence of an electrophysiological
      difference points to a dissociation between electrophysiological and hemodynamic
      responses and may be of importance for the understanding of flow coupling.

PMID- 14583407
TI  - LABORAS: Initial pharmacological validation of a system allowing continuous
      monitoring of laboratory rodent behaviour.
AB  - A newly developed apparatus for automated behavioural analysis, Laboratory Animal
      Behaviour Observation, Registration and Analysis System (LABORAS), has been
      further validated with respect to the ability of the system to detect the
      pharmacodynamic effects of standard pharmacological tools. Data were obtained
      from rats administered with mCPP (reversal with SB242084), 8-OH-DPAT (reversal
      with WAY100635), amphetamine (reversal with haloperidol) and angiotensin, with
      the focus on locomotor activity, feeding and drinking behaviours. The data
      captured and analysed by LABORAS, suggests that the automated system is able to
      detect pharmacologically induced changes in behaviour, reliably and efficiently,
      with a significant reduction in the number of animals required, and reduced
      operator input.

PMID- 14583408
TI  - Automated sleep staging in rat with a standard spreadsheet.
AB  - A new method of automated sleep-wake staging in the rat is described. Hippocampal
      electroencephalographic (HPC) and nuchal electromyographic signals were recorded
      by a digital polygraph. The HPC channel was filtered off-line to obtain the
      original plus theta and delta waves. Statistics of each of these four channels
      were obtained every 5 s and exported to a standard spreadsheet. The automated
      staging consisted of five steps: (1) automatic detection of waking, nonrapid eye
      movement sleep and rapid eye movement sleep patterns (5-s periods); (2)
      calculation of statistics for each vigilance state; (3) final classification of 5
      s periods; (4) construction of a primary 20-s epoch hypnogram; and (5) automatic
      refinement of the previous hypnogram. The system includes indices about the
      accuracy of the staging and was validated with five recordings of 23 h each. The
      global agreement between human and automatic scoring in the validation recordings
      was 94.32%.

PMID- 14583409
TI  - Negative self-imagery blocks inferences.
AB  - Previous research has shown that, unlike non-anxious individuals, people with
      social phobia fail to generate non-threatening inferences when ambiguous social
      information is first encountered (i.e. 'on-line'; Hirsch and Mathews Journal of
      Abnormal Psychology, 109 (2000) 705-712). Patients with social phobia also report
      negative self-imagery in social situations, while individuals without high social
      anxiety do not. The negative self-imagery in social phobia may prevent the
      generation of non-threatening inferences. If so, then training non-anxious
      individuals to hold in mind a negative self-image should remove the 'on-line' non
      threat inferential bias normally evident in this population. In the present
      study, low anxious volunteers were allocated to negative image training or a
      control task that did not manipulate self-imagery. Following negative image
      training, or the control task, volunteers read descriptions of job interviews and
      at certain points during the text performed lexical decisions. Some decisions
      were made after ambiguous text that could have been interpreted in both a
      threatening and a non-threatening manner. In a baseline condition, decisions were
      made following the text for which there was only one possible inference (either
      threat or non-threat). The results for the control group replicated earlier
      findings of a non-threat inferential bias for non-anxious individuals. In
      contrast, and as predicted, non-anxious volunteers who were trained to hold a
      negative image in mind lacked any non-threatening inferential bias, and also
      experienced higher levels of state anxiety.

PMID- 14583410
TI  - The relationship between disgust sensitivity, anxiety and obsessions.
AB  - Three hundred participants, including volunteers from an obsessional support
      group, filled in questionnaires relating to disgust sensitivity, health anxiety,
      anxiety, fear of death, fear of contamination and obsessionality as part of an
      investigation into the involvement of disgust sensitivity in types of obsessions.
      Overall, the data supported the hypothesis that a relationship does exist between
      disgust sensitivity and the targeted variables. A significant predictive
      relationship was found between disgust sensitivity and total scores on the
      obsessive compulsive inventory (OCI; Psychological Assessment 10 (1998) 206) for
      both frequency and distress of symptomatology. Disgust sensitivity scores were
      significantly related to health anxiety scores and general anxiety scores and to
      all the obsessional subscales, with the exception of hoarding. Additionally,
      multiple regression analyses revealed that disgust sensitivity may be more
      specifically related to washing compulsions: frequency of washing behaviour was
      best predicted by disgust sensitivity scores. Washing distress scores were best
      predicted by health anxiety scores, though disgust sensitivity entered in the
      second model. It is suggested that further research on the relationship between
      disgust sensitivity and obsessionality could be helpful in refining the
      theoretical understanding of obsessions.

PMID- 14583411
TI  - Confirmatory factor analysis of the Penn State Worry Questionnaire: Multiple
      factors or method effects?
AB  - The latent structure of the Penn State Worry Questionnaire (PSWQ) was evaluated
      with confirmatory factor analyses (CFAs) in 1200 outpatients with DSM-IV anxiety
      and mood disorders. Of particular interest was the comparative fit and
      interpretability of a two-factor solution (cf. Behaviour Research and Therapy 40
      (2002) 313) vs. a one-factor model that specified method effects arising from
      five reverse-worded items. Consistent with prediction, the superiority of the one
      factor model was demonstrated in split-sample CFA replications (ns=600). Multiple
      group CFAs indicated that the measurement properties of the PSWQ were invariant
      in male and female patients. In addition to their direct relevance to the
      psychometrics of the PSWQ, the results are discussed in regard to methodological
      considerations for using factor analytic methods in the evaluation of
      psychological tests.

PMID- 14583412
TI  - The Anxiety Sensitivity Index - Revised: psychometric properties and factor
      structure in two nonclinical samples.
AB  - Anxiety sensitivity (AS) is the fear of anxiety-related sensations based on
      beliefs about their harmful consequences. Despite its status as the most popular
      measure of AS, the anxiety sensitivity index is too abbreviated to adequately
      measure the somatic, cognitive, and social facets of the construct. The Anxiety
      Sensitivity Index - Revised (ASI-R) is a revised and expanded version of the ASI
      that was developed to improve the assessment of AS and its dimensions. The
      present study was conducted to examine the psychometric properties and factor
      structure of the ASI-R. Two large undergraduate samples completed a psychometric
      assessment package that included the ASI-R and measures of anxiety, depression,
      and related constructs. Exploratory factor analysis revealed four lower-order ASI
      R factors: (1) beliefs about the harmful consequences of somatic sensations; (2)
      fear of publicly observable anxiety reactions; (3) fear of cognitive dyscontrol;
      and (4) fear of somatic sensations without explicit consequences. These factors
      loaded on a single, higher-order factor. Correlations between the ASI-R factors
      and related variables were consistent with AS theory. Results across both samples
      in the present study were highly similar. The strengths and limitations of the
      ASI-R are discussed, and the implications of our findings for the nature and
      measurement of AS are considered.

PMID- 14583413
TI  - Depersonalisation disorder: a cognitive-behavioural conceptualisation.
AB  - Depersonalisation (DP) and derealisation (DR) are subjective experiences of
      unreality in, respectively, one's sense of self and the outside world. These
      experiences occur on a continuum from transient episodes that are frequently
      reported in healthy individuals under certain situational conditions to a chronic
      psychiatric disorder that causes considerable distress (depersonalisation
      disorder, DPD). Despite the relatively high rates of reporting these symptoms,
      little research has been conducted into psychological treatments for this
      disorder. We suggest that there is compelling evidence to link DPD with the
      anxiety disorders, particularly panic. This paper proposes that it is the
      catastrophic appraisal of the normally transient symptoms of DP/DR that results
      in the development of a chronic disorder. We suggest that if DP/DR symptoms are
      misinterpreted as indicative of severe mental illness or brain dysfunction, a
      vicious cycle of increasing anxiety and consequently increased DP/DR symptoms
      will result. Moreover, cognitive and behavioural responses to symptoms such as
      specific avoidances, 'safety behaviours' and cognitive biases serve to maintain
      the disorder by increasing awareness of the symptoms, heightening the perceived
      threat and preventing disconfirmation of the catastrophic misinterpretations. A
      coherent model facilitates the development of potentially effective cognitive and
      behavioural interventions.

PMID- 14583414
TI  - Worst-point suicidal plans: a dimension of suicidality predictive of past suicide
      attempts and eventual death by suicide.
AB  - Among 440 psychiatric outpatients with current suicidal ideation, we examined the
      empirical distinction between the "plans" vs. "desire" dimensions of suicidality,
      focusing for conceptual and empirical reasons on a worst-point assessment
      strategy. Factor analyses were consistent with the distinction, but more
      importantly, among the current ideators included in this study, the worst-point
      "plans" dimension was the only predictor significantly related to both of two
      important indices, history of past attempt and eventual suicide. These findings
      bear on the trajectory of suicidal behavior over time, as well as inform the
      clinical assessment of suicidal patients.

PMID- 14583415
TI  - Interpretation and judgmental biases in social phobia.
AB  - Previous research demonstrated that social phobia is characterized by content
      specific interpretation and judgmental biases. The present study investigated
      whether this interpretation bias occurs not only in ambiguous, but also in
      positive and negative social events, and whether social phobic patients (SPs) are
      more characterized by a judgmental bias in costs than in probability. Besides, we
      argued that the judgmental bias observed in former studies could also be
      attributed to accurate estimations of SPs (of, for example, stuttering).
      Therefore, we assessed judgmental bias by the ratings of probability and costs of
      a negative evaluation (e.g. 'people dislike me') and not, as in previous studies,
      of negative social events (e.g. 'stuttering'). SPs (n=228) and normal controls
      (n=33) were presented social and non-social events ranging from positive to
      profoundly negative. They ranked four different interpretations on likelihood to
      assess interpretation bias, and rated the profoundly negative interpretation on
      probability and cost to assess judgmental bias. SPs demonstrated content-specific
      interpretation and judgmental biases that also occurred in positive and negative
      social events. In contrast with expectations, SPs were characterized by a
      judgmental bias in both costs and probability.

PMID- 14583416
TI  - Treatment of adult patients with congenital adrenal hyperplasia due to 21
      hydroxylase deficiency: a clinical practice audit.
AB  - OBJECTIVE: To review one physician's management of glucocorticoid replacement
      therapy in adult patients with congenital adrenal hyperplasia (CAH) due to 21
      hydroxylase deficiency and to determine the efficacy and the range of effective
      doses of dexamethasone in managing the clinical and biochemical consequences of
      this disorder. METHODS: We conducted a retrospective clinical practice audit of
      nine patients treated by a single physician for 21-hydroxylase deficiency during
      the period from March 1998 to January 2002. We documented biochemical control and
      clinical features of glucocorticoid excess or deficiency for various doses of
      dexamethasone. RESULTS: The final dosage of dexamethasone needed to normalize
      serum 17-hydroxyprogesterone levels, to arrest progression of hirsutism, and to
      eliminate the symptoms and signs of adrenocortical insufficiency while avoiding
      manifestations of glucocorticoid excess ranged from 0.0625 to 0.875 mg/day, with
      a mean dosage of 0.4 mg/day. Seven patients had adequate control during the
      observation period with use of dosages of dexamethasone of 0.5 mg/day or less.
      CONCLUSION: Adequate control of 21-hydroxylase can be achieved with relatively
      low doses of dexamethasone; thus, the long-held notion that 0.75 mg of
      dexamethasone is "equivalent" in glucocorticoid effect to the estimated daily
      production of cortisol is challenged. These data suggest that physicians should
      evaluate the doses of glucocorticoids used in their patients with CAH and other
      forms of primary and central adrenocortical insufficiency because considerable
      decreases in glucocorticoid doses may be in order.

PMID- 14583417
TI  - Effects of kelp supplementation on thyroid function in euthyroid subjects.
AB  - OBJECTIVE: To study the effects of ingestion of two different doses of
      supplemental kelp on the thyroid function of healthy euthyroid subjects. METHODS:
      We conducted a double-blind prospective clinical trial involving 36 healthy
      euthyroid subjects, who were randomly assigned to receive placebo (4 alfalfa
      capsules per day), low-dose kelp (2 kelp capsules and 2 alfalfa capsules per
      day), or high-dose kelp (4 kelp capsules per day) for 4 weeks. Thyrotropin
      (thyroid-stimulating hormone or TSH), free thyroxine, and total triiodothyronine
      were assessed at weeks 0, 4, and 6. Response to thyrotropin-releasing hormone
      stimulation, urinary iodine excretion, and basal metabolic rate were determined
      at weeks 0 and 4. RESULTS: TSH concentrations did not differ significantly
      between week 0 and week 4 in the placebo group (P = 0.16) but increased
      significantly in both the low-dose kelp (P = 0.04) and high-dose kelp (P = 0.002)
      groups. Free thyroxine concentrations decreased slightly but significantly after
      4 weeks of placebo but were unchanged in the low-dose and the high-dose kelp
      groups. In contrast, total triiodothyronine levels did not differ significantly
      after 4 weeks of placebo or low-dose kelp therapy but were significantly
      decreased after high-dose kelp therapy (P = 0.04). Similarly, the thyrotropin
      releasing hormone stimulation test showed no significant change in
      poststimulation TSH after 4 weeks in the placebo or low-dose kelp groups but
      revealed a significantly increased response after high-dose kelp therapy (P =
      0.0002). The 24-hour urinary iodine excretion showed dose-dependent increases in
      the two kelp study groups. Basal metabolic rate did not change significantly in
      any study group during the 4-week study period. All thyroid laboratory values
      returned to baseline 2 weeks after cessation of kelp supplementation, except for
      TSH in the high-dose kelp group, which was significantly decreased. CONCLUSION:
      Short-term dietary supplementation with kelp significantly increases both basal
      and poststimulation TSH. These findings corroborate previous studies on the
      effects of supplemental iodide given to euthyroid subjects for a similar period.
      Further studies are needed to determine whether long-term kelp supplementation
      would cause clinically significant thyroid disease.

PMID- 14583418
TI  - Epidemic of gynecomastia among haitian refugees: exposure to an environmental
      antiandrogen.
AB  - OBJECTIVE: To investigate an observed epidemic of gynecomastia among Haitian
      refugees in US detention centers in 1981 and 1982. METHODS: All identifiable
      environmental exposures were investigated for estrogenic and antiandrogenic
      activity. RESULTS: A high incidence of gynecomastia was observed among Haitian
      refugees in five detention centers in the United States. Of 284 men screened, 20
      (from 18 to 53 years old) demonstrated new-onset gynecomastia (Tanner stages 2 to
      5) in June 1982. The mean onset of gynecomastia was 130 +/- 12 days after arrival
      in the United States. Other symptoms included loss of libido (in all 20 patients)
      and decreased beard growth (in 10). Plasma concentrations of luteinizing hormone,
      follicle-stimulating hormone, prolactin, testosterone, and estradiol were not
      significantly different from those in 20 age-matched control subjects.
      Environmental substances, including tap water and the delousing agents Kwell
      shampoo and R&C Spray (applied to bedding and clothing), were tested for
      estrogenicity and androgenicity. None of these substances bound to cytosol
      estrogen receptors. The delousing agents were assayed for androgen binding by
      using genital skin fibroblasts. R&C Spray competed equally with testosterone for
      androgen-binding sites. Phenothrin, the "multi-cide" component of R&C Spray,
      reproduced this competitive binding result. When tested for antiandrogenic
      effects on prostate growth by using immature male rats treated with testosterone
      filled Silastic capsules, phenothrin antagonized androgen action, as demonstrated
      by decreased prostate weights. CONCLUSION: The antiandrogenic activity of
      phenothrin may explain this unusual epidemic of gynecomastia.

PMID- 14583419
TI  - Pseudopheochromocytoma of pregnancy.
AB  - OBJECTIVE: To report a diagnostically challenging case of preeclampsia. METHODS:
      We present a case report with clinical, biochemical, imaging, and
      immunohistochemical findings. In addition, the clinical features of
      pheochromocytoma during pregnancy are reviewed, and the challenges in
      distinguishing it from preeclampsia are discussed. RESULTS: A 33-year-old woman
      presented at 14 weeks' gestational age with severe hypertension. Evaluation for
      secondary causes of hypertension were prompted by difficulty controlling the
      blood pressure and associated symptoms of headache and nausea. Investigations
      revealed high levels of urinary catecholamines, in conjunction with increased
      uptake of (111)In-labeled octreotide in the midabdominal area. At 28 weeks'
      gestation, worsening of blood pressure, high liver enzyme levels, and proteinuria
      necessitated a cesarean delivery and concomitant hysterectomy. Blood pressure and
      urinary catecholamine excretion promptly normalized after delivery. Pathologic
      examination of the uterus and placenta demonstrated no expression of
      neuroendocrine markers including chromogranin, but the trophoblast demonstrated
      strong immunostaining for tyrosine hydroxylase. Expression of this rate-limiting
      enzyme responsible for catecholamine synthesis may have contributed to the
      pathogenesis of preeclampsia in this patient. CONCLUSION: This case demonstrates
      that severe pre-eclampsia may mimic pheochromocytoma.

PMID- 14583420
TI  - Spontaneous long-term remission in a patient with premature ovarian failure.
AB  - OBJECTIVE: To describe a patient with premature ovarian failure who after a
      pregnancy achieved a prolonged remission, which has lasted for more than 10
      years. METHODS: Clinical and laboratory data of a patient who had premature
      ovarian failure with a spontaneous pregnancy and a prolonged remission are
      described. The pertinent literature is reviewed and summarized. RESULTS: A 26
      year-old woman presented with secondary amenorrhea of 6 months' duration in 1984.
      Her serum total estrogen level was low, and gonadotropins were in the
      postmenopausal range. She also had a history of primary hypothyroidism, diagnosed
      in 1979. The physical examination showed normal findings, except for an enlarged
      thyroid gland and a few areas of vitiligo on her back, arms, and legs.
      Antithyroid antibodies were present. Adrenal insufficiency was excluded on the
      basis of results of the cosyntropin stimulation test. She had a normal 46,XX
      karyotype. A diagnosis of premature ovarian failure was made, and therapy with
      cyclic estrogen and progesterone was initiated. In 1991, she spontaneously
      conceived and gave birth to a healthy baby. After delivery, the patient began to
      have normal menstrual cycles and continues to do so without hormone replacement
      therapy. Subsequently, serum estrogen and gonadotropins were in the normal range.
      Her thyroid antibodies also became negative. When last contacted by her primary
      care physician in November 2002, she was still having normal menstrual periods,
      and the patches of vitiligo were no longer present. CONCLUSION: It is well known
      that many autoimmune diseases subside during pregnancy; however, most of them
      relapse in the postpartum period. The mechanism of the prolonged remission in our
      patient is unknown, but hormonal as well as autoimmune changes related to
      pregnancy and the post partum period might have had a role.

PMID- 14583421
TI  - Schmidt'S syndrome and severe hyponatremia: report of an unusual case and review
      of the related literature.
AB  - OBJECTIVE: To describe a rare case of profound hyponatremia in a male patient
      with autoimmune polyglandular syndrome type 2 (Schmidt's syndrome). METHODS: We
      present the clinical and laboratory data in our patient and review the related
      published reports from the English language literature on the association of
      hyponatremia with Schmidt's syndrome. RESULTS: A 31-year-old man presented to the
      emergency department because of nausea, anorexia, and weakness for 6 days. He was
      found to have severe hyponatremia (serum sodium concentration, 101 mEq/L) and
      mild hyperkalemia. Endocrine testing revealed the presence of Addison's disease
      and severe primary hypothyroidism, consistent with Schmidt's syndrome. The
      patient responded to treatment with volume and hormone replacement. An extensive
      literature search disclosed only one previously reported case (of a female
      patient) in which Schmidt's syndrome led to the development of a degree of
      hyponatremia as severe as that in our patient. CONCLUSION: Concomitant occurrence
      of primary adrenal insufficiency and primary hypothyroidism can result in a
      greater degree of hyponatremia than would be expected from either disease alone.
      Likely explanations include the additive effects of primary hypothyroidism and
      adrenal failure in the development of hyponatremia and, possibly, in some
      patients exquisite renal sensitivity to hemodynamic changes and altered hormonal
      status.

PMID- 14583422
TI  - Primary ovarian lymphoma manifesting with severe hypercalcemia.
AB  - OBJECTIVE: To describe a case of primary ovarian lymphoma manifesting with severe
      hypercalcemia. METHODS: We report the occurrence of a substantially increased
      serum calcium level in a 74-year-old female patient who presented with
      progressive weakness, volume depletion, confusion, slurred speech, cardiac
      abnormalities, and renal insufficiency. The patient's clinical course is
      reviewed, and the results of laboratory and imaging studies leading to the
      underlying diagnosis are presented. RESULTS: Initial evaluation revealed
      hemodynamic instability, disorientation, cardiac rhythm abnormalities, high
      levels of blood urea nitrogen and creatinine, and a serum calcium level of 18
      mg/dL. A cranial computed tomographic scan showed no evidence of pronounced
      atrophy or stroke. Aggressive rehydration was initiated, and a permanent
      pacemaker was inserted. A suppressed level of parathyroid hormone and a high
      serum 1,25-dihy-droxyvitamin D concentration were found, but no evidence of
      granulomatous disease, infection, or overt malignant lesion was detected. The
      patient showed clinical improvement and was dismissed from the hospital, but the
      hypercalcemic state recurred soon thereafter. A computed tomographic scan of the
      abdomen and pelvis revealed a pelvic mass, which was diagnosed as ovarian
      lymphoma after surgical removal. The serum calcium and 1,25-dihy-droxyvitamin D
      levels normalized postoperatively. CONCLUSIONS: Primary ovarian lymphoma can be a
      cause of, and can manifest solely as, a severe and symptomatic increase in the
      serum calcium level, which is mediated by an increased serum concentration of
      1,25-dihy-droxyvitamin D. It should be considered in the differential diagnosis
      of unexplained nonparathyroid hypercalcemia.

PMID- 14583424
TI  - Asymptomatic primary hyperparathyroidism: standards and guidelines for diagnosis
      and management in Canada: Consensus Development Task Force on Diagnosis and
      Management of Asymptomatic Primary Hyperparathyroidism position paper.

PMID- 14583423
TI  - Cushing's syndrome due to ectopic production of corticotropin-releasing hormone
      in an infant with ganglioneuroblastoma.
AB  - OBJECTIVE: To report the first recognized case of Cushing's syndrome due to a
      corticotropin-releasing hormone (CRH)-secreting ganglioneuroblastoma, which was
      found in an 18-month-old boy with hypertensive encephalopathy. METHODS: The
      clinical, biochemical, and immunohistochemical characteristics of this rare
      syndrome are described, and the relevant literature is reviewed. RESULTS: An 18
      month-old boy with a history of recent weight gain was admitted because of sudden
      onset of right fixed esotropia and left facial palsy after episodes of emesis.
      Magnetic resonance imaging showed old left frontal lobe and right hypothalamic
      infarcts. The patient had generalized obesity, decelerated linear growth,
      hypertrichosis, hypertension (144/103 mm Hg), hypokalemia, and proteinuria. The
      24-hour urinary excretion of free cortisol, catecholamines, and metanephrines was
      increased. The serum cortisol concentration after a 1-mg overnight dexamethasone
      suppression test (DST) was 53.7 mg/dL (normal, <5). The serum adrenocorticotropic
      hormone (ACTH) concentration was 7 pg/mL (normal, 10 to 60), and the CRH level
      was 439 pg/mL (normal, 24 to 40). An overnight high-dose DST (8 mg) failed to
      suppress serum cortisol; however, both cortisol and ACTH were responsive to ovine
      CRH stimulation. Despite discordant dynamic endocrine testing and negative
      somatostatin receptor scintigraphy, computed tomography showed a right 3.6- by
      3.0-cm extra-adrenal retroperitoneal mass with central calcification extending 7
      cm cephalocaudally. The patient underwent exploratory laparotomy, followed by
      chemotherapy. Findings on light microscopic and immunohistochemical examination
      of the retroperitoneal mass were consistent with a ganglioneuroblastoma that
      expressed CRH, pro-opiomelanocortin, and ACTH. CONCLUSION: The evaluation of
      Cushing's syndrome is one of the most complex endocrine challenges. In this case,
      it was due to ectopic production of CRH by a ganglioneuroblastoma. Because most
      CRH-producing tumors also secrete ACTH, the ectopic production may represent a
      paracrine phenomenon in addition to an endocrine phenomenon. The ectopic CRH may
      also indirectly provoke pituitary ACTH secretion. This dual mechanism may explain
      the resistance of the tumor to feedback inhibition and a CRH-stimulation response
      indistinguishable from that observed in pituitary-dependent Cushing's syndrome.

PMID- 14583425
TI  - Thiazolidinediones, peripheral edema, and type 2 diabetes: incidence,
      pathophysiology, and clinical implications.
AB  - OBJECTIVE: To present an objective, evidence-based review of edema associated
      with thiazolidinedione use in patients with type 2 diabetes. METHODS: We review
      the incidence, pathophysiology, and clinical significance of edema associated
      with the use of thiazolidinediones, with specific emphasis on the two currently
      available thiazolidinediones, rosiglitazone and pioglitazone. RESULTS: Both
      pioglitazone and rosiglitazone have been associated with increased development of
      edema in clinical trials. The incidence of edema in these trials varies from
      about 3.0 to 7.5% with the thiazolidinediones compared with 1.0 to 2.5% with
      placebo or other oral antidiabetic therapy. The highest incidence of edema has
      been reported when thiazolidinediones are used in combination with insulin. In
      clinical studies, these patients have an incidence of edema of 15.3% when treated
      with insulin plus pioglitazone and 14.7% when treated with insulin plus
      rosiglitazone (compared with 7.0% and 5.4% in the insulin-only groups,
      respectively). In addition to peripheral edema, reports have described pulmonary
      edema associated with thiazolidinedione therapy. In all such reports, patients
      failed to respond to diuretics during use of thiazolidinediones. Clinical
      improvement ensued only after discontinuation of thiazolidinedione therapy.
      Therefore, thiazolidinediones either may have some effect on the delivery of
      diuretics to the lumen of the nephron or may induce tubular alterations that
      impair the ability of the nephrons to respond to diuretics. Several potential
      causes have been postulated to precipitate edema in patients with diabetes who
      are treated with these agents: increased plasma volume, increased renal sodium
      reabsorption, reflex sympathetic activation, alteration of intestinal ion
      transport, and increased production of vascular endothelial growth factor.
      CONCLUSION: Available evidence suggests that edema is a class effect of the
      thiazolidinediones and is multifactorial in origin. Thiazolidinedione-associated
      edema seems to be dose related and occurs most frequently when thiazolidinediones
      are used in combination with insulin. Hence, therapy with these agents should be
      initiated at low doses, and patients should undergo assessment for edema and
      congestive heart failure during the first few weeks of treatment. Caution should
      be exercised when thiazolidine-diones are used in those at risk for or with a
      history of heart failure. Options for management thiazolidinedione-associated
      edema include dose reduction, drug discontinuation, and symptomatic therapy with
      diuretics. Further studies are needed to elucidate the mechanisms responsible for
      the cause of edema in patients with type 2 diabetes treated with
      thiazolidinediones and to determine whether certain factors might predict
      susceptibility to development of edema and congestive heart failure.

PMID- 14583426
TI  - American Association of Clinical Endocrinologists medical guidelines for the
      clinical use of dietary supplements and nutraceuticals.

PMID- 14583427
TI  - Rain, reign, rein--the tyranny of IT.

PMID- 14583428
TI  - Thionamide-induced agranulocytosis.

PMID- 14583429
TI  - Visual vignette. Cabergoline therapy.

PMID- 14583430
TI  - Visual vignette. Primary pachydermoperiostosis or Touraine-Solente-Gole syndrome.

PMID- 14583431
TI  - Vitamin D3 upregulates plasma membrane Ca2+-ATPase expression and potentiates
      apico-basal Ca2+ flux in MDCK cells.
AB  - Plasma membrane Ca2+-ATPases (PMCAs) are a ubiquitous system for the expulsion of
      Ca2+ from eukaryotic cells. In tight monolayers of polarized Madin-Darby canine
      kidney (MDCK) cells representing a distal kidney tubule model, PMCAs are
      responsible for about one-third of the vectorial Ca2+ transport under resting
      conditions, with the remainder being provided by the Na+/Ca2+ exchanger. Vitamin
      D3 (VitD) is known to increase PMCA expression and activity in Ca2+-transporting
      tissues such as the intestine, as well as in osteoblasts and Madin-Darby bovine
      kidney epithelial cells. We found that VitD upregulated the expression of the
      PMCAs (mainly PMCA4b) in MDCK cell lysates at the RNA and protein level in a time
      and dose-dependent manner. Interestingly, VitD caused a decrease of the PMCAs in
      the apical plasma membrane fraction and a concomitant increase of the pumps in
      the basolateral membrane. Functional studies demonstrated that transcellular
      45Ca2+ flux from the apical-to-basolateral compartment was significantly enhanced
      by VitD. These findings demonstrate that VitD is a positive regulator of the
      PMCAs in MDCK epithelial cells. The correlation of decreased apical/increased
      basolateral expression of the PMCAs with an increase in transcellular Ca2+ flux
      from the apical (urine) toward the basolateral (blood) compartment indicates the
      physiological relevance of VitD function in kidney tubular Ca2+ reabsorption.

PMID- 14583432
TI  - Chronic nitric oxide synthase inhibition exacerbates renal dysfunction in
      cirrhotic rats.
AB  - The present study investigated sodium balance and renal tubular function in
      cirrhotic rats with chronic blockade of the nitric oxide (NO) system. Rats were
      treated with the nonselective NO synthase inhibitor NG-nitro-l-arginine methyl
      ester (l-NAME) starting on the day of common bile duct ligation (CBL). Three
      weeks of daily sodium balance studies showed that CBL rats developed sodium
      retention compared with sham-operated rats and that l-NAME treatment dose
      dependently deteriorated cumulative sodium balance by reducing urinary sodium
      excretion. Five weeks after CBL, renal clearance studies were performed, followed
      by Western blotting of the electroneutral type 3 sodium/proton exchanger (NHE3)
      and the Na-K-ATPase present in proximal tubules. Untreated CBL rats showed a
      decreased proximal reabsorption with a concomitant reduction of NHE3 and Na-K
      ATPase levels, indicating that tubular segments distal to the proximal tubules
      were responsible for the increased sodium reabsorption. l-NAME-treated CBL rats
      showed an increased proximal reabsorption measured by the lithium clearance
      method and showed a marked increase in NHE3 and Na-K-ATPase protein levels. Our
      results show that chronic l-NAME treatment exacerbates the sodium retention found
      in CBL rats by a significant increase in proximal tubular reabsorption.

PMID- 14583433
TI  - Angiotensin II induces thrombospondin-1 production in human mesangial cells via
      p38 MAPK and JNK: a mechanism for activation of latent TGF-beta1.
AB  - ANG II induces secretion and activation of transforming growth factor-beta (TGF
      beta) by glomerular mesangial cells. However, the mechanisms that operate this
      are unclear. Thrombospondin-1 (TSP-1), which is produced by mesangial cells in
      damaged glomeruli, is one of several molecules known to activate the latent TGF
      beta1 complex. Therefore, we examined whether the ANG II-induced activation of
      latent TGF-beta1 in human mesangial cells (HMC) operates via TSP-1. The addition
      of ANG II (1-100 nM) to HMC significantly increased TSP-1 mRNA within 6 h,
      followed by an increase in TSP-1 protein production as shown by Western blot
      analysis of cells and immunoassay of the culture supernatant. Production of ANG
      II-induced TSP-1 mRNA and protein was completely inhibited by an ANG II type 1
      (AT1)-receptor antagonist but was unaffected by an AT2-receptor antagonist. Use
      of a TSP-1-specific blocking peptide demonstrated that the ANG II-induced
      activation of latent TGF-beta1 operates via TSP-1. Next, we investigated the role
      of ERK1/2, p38 MAPK, and JNK in ANG II-induced TSP-1 production in HMC. The
      addition of the upstream ERK1/2 inhibitor PD-98059 did not affect ANG II-induced
      TSP-1 production, whereas addition of either the p38 MAPK inhibitor SB-203580 or
      the JNK inhibitor SP-600125 significantly reduced TSP-1 production. In
      conclusion, this study has demonstrated that ANG II-induced activation of latent
      TGF-beta1 in HMC operates via TSP-1. Furthermore, ANG II-induced TSP-1 production
      is dependent on p38 MAPK and JNK signaling.

PMID- 14583434
TI  - The renal retinoid system: time-dependent activation in experimental
      glomerulonephritis.
AB  - Retinoids reduce renal damage in rat experimental glomerulonephritis. It is
      unknown, however, how local and systemic retinoid pathways respond to renal
      injury. We used a rat model of artificially induced acute anti-Thy1.1-nephritis
      (THY-GN). We examined the extrarenal and glomerular expression of the retinol
      (RoDH) and retinal (RalDH) dehydrogenases 1 and 2 as well as the expression of
      the retinoic acid (RAR) and retinoid X (RXR) receptor subtypes alpha, beta, and
      gamma. Furthermore, we investigated serum and glomerular retinoid concentration
      patterns. On days 3, 7, and 14, we compared nonnephritic rats (control group;
      CON) to THY-GN rats with respect to systolic blood pressure and glomerular cell
      count per cross section. Systolic blood pressure and glomerular cell count were
      significantly higher in THY-GN rats on days 7 and 14 (P < 0.001). We found a 60%
      reduction in expression levels for retinoid receptors and dehydrogenases in
      nephritic glomeruli on day 3, but a threefold increase on day 7 (P < 0.001 vs.
      CON). The same applies to RAR alpha protein. Hepatic expression of retinoid
      receptors was not influenced. On day 14, glomerular expression levels for
      retinoid receptors and retinoid-metabolizing enzymes had returned to a normal
      level, glomerular cell count being still increased. Administering 13-cis retinoic
      acid (isotretinoin) lowered blood pressure and glomerular cell count in nephritic
      rats but failed to influence the glomerular expression of retinoid receptors or
      retinoid-metabolizing enzymes. Our data document a stimulation of glomerular
      retinoid-synthesizing enzymes and expression of retinoid receptors in the early
      repair phase of THY-GN, suggesting activation of this system in acute renal
      disease.

PMID- 14583435
TI  - T-type calcium channels in the regulation of afferent and efferent arterioles in
      rats.
AB  - L-type Ca2+ channels predominantly influence preglomerular arterioles, but there
      is less information regarding the role of T-type Ca2+ channels in regulating the
      renal microvasculature. We compared the effects of T- and L-type channel blockade
      on afferent and efferent arterioles using the in vitro blood-perfused
      juxtamedullary nephron preparation. Single afferent or efferent arterioles of
      Sprague-Dawley rats were visualized and superfused with solutions containing Ca2+
      channel blockers. We confirmed that L-type channel blockade with diltiazem
      dilates afferent arterioles but has no significant effects on efferent
      arterioles. In contrast, T-type channel blockade with pimozide (10 micromol/l) or
      mibefradil (1 micromol/l) dilated both afferent (26.8 +/- 3.4 and 24.6 +/- 1.9%)
      and efferent (19.2 +/- 2.9 and 19.1 +/- 4.8%) arterioles. Adding diltiazem did
      not significantly augment the dilation of afferent arterioles elicited by
      pimozide and mibefradil, and adding pimozide after diltiazem likewise did not
      elicit further vasodilation. Diltiazem blocked the depolarization-induced
      afferent arteriolar constriction elicited by 55 mM KCl; however, the constrictor
      response to KCl remained intact during treatment with 10 microM pimozide.
      Pimozide also prevented the afferent arterioles from exhibiting autoregulatory
      mediated constrictor responses to increases in perfusion pressure. We conclude
      that T-type channel blockers dilate efferent arterioles as well as afferent
      arterioles and diminish afferent arteriolar autoregulatory responses to changes
      in perfusion pressure. To the extent that these agents exert their effects
      primarily on T-type Ca2+ channels in our experimental setting, these results
      indicate that T-type channels are functionally expressed in juxtamedullary
      afferent and efferent arterioles and may act cooperatively with L-type channels
      to regulate afferent arteriolar resistance. Because L-type channels are not
      functionally expressed in efferent arterioles, T-type channels may be
      particularly significant in the regulation of efferent arteriolar function.

PMID- 14583436
TI  - Hypoxia upregulates von Hippel-Lindau tumor-suppressor protein through RhoA
      dependent activity in renal cell carcinoma.
AB  - A key task for the multifunctional von Hippel-Lindau protein (pVHL) is regulation
      of the activity of hypoxia-inducible factor-1alpha (HIF-1alpha) by targeting it
      to the proteasome for degradation under normoxia. pVHL binding to HIF-1alpha is
      lost under low O2 tension, leading to transcription of several genes involved in
      the hypoxia response. However, regulation of pVHL by hypoxia remains to be
      investigated. We evaluated the effects of hypoxia on pVHL expression in carcinoma
      and endothelial cells. We showed that hypoxia stimulates pVHL levels (2.5-fold)
      in renal Caki-1 cells expressing wild-type VHL (VHL+/+). This upregulation was
      independent of VHL status, because hypoxia also increased pVHL expression in
      renal 786-O cells carrying mutated VHL (VHL-/-). Hypoxia did not affect pVHL
      expression in endothelial cells. Hypoxia-induced pVHL in Caki-1 cells was RhoA
      dependent, because inhibition by exotoxin C3 prevented pVHL stimulation.
      Furthermore, inhibition of Rho kinase by Y-27632 blocked pVHL induction by
      hypoxia. During normoxia, pVHL expression was also induced in cells transfected
      with dominant-active RhoA. Furthermore, disruption of actin organization by
      chemical agents or by hypoxia stimulated pVHL expression in kidney cells. On the
      other hand, inhibition of MAP kinases p38 and JNK, but not MAP kinase kinase
      (MEK1/2), reduced pVHL upregulation by 30 and 72%, respectively, during hypoxia,
      supporting a significant role for these signaling pathways. Expression and
      phosphorylation of c-Jun were stimulated in cells transfected with dominant
      active RhoA. Together, these findings demonstrate that hypoxia induces pVHL
      expression in renal cancer cells, and this induction is mediated by RhoA
      dependent pathways.

PMID- 14583437
TI  - Overexpression of angiotensin type 2 receptor ameliorates glomerular injury in a
      mouse remnant kidney model.
AB  - Angiotensin II mediates the progression of renal disease through the type 1
      receptor (AT(1)R). Recent studies have suggested that type 2 receptor (AT(2)R)
      mediated signaling inhibits cell proliferation by counteracting the actions of
      AT(1)R. The aim of the present study was to determine the effect of AT(2)R
      overexpression on glomerular injury induced by (5/6) nephrectomy ((5/6)Nx).
      AT(2)R transgenic mice (AT(2)-Tg), overexpressing AT(2)R under the control of
      alpha-smooth muscle actin (alpha-SMA) promoter, and control wild-type mice (Wild)
      were subjected to (5/6)Nx. In AT(2)-Tg mice, the glomerular expression of AT(2)R
      was upregulated after (5/6)Nx. Urinary albumin excretion at 12 wk after (5/6)Nx
      was decreased by 33.7% in AT(2)-Tg compared with Wild mice. Glomerular size in
      AT(2)-Tg mice was significantly smaller than in Wild mice after (5/6)Nx (93.1 +/-
      3.0 vs. 103.3 +/- 1.8 microm; P < 0.05). Immunohistochemistry revealed
      significant decreases in glomerular expression of platelet-derived growth factor
      BB chain (PDGF-BB) and transforming growth factor-beta(1) (TGF-beta(1)) in AT(2)
      Tg with (5/6)Nx compared with Wild mice. Urinary excretion of nitric oxide
      metabolites was increased 2.5-fold in AT(2)-Tg compared with Wild mice. EMSA
      showed that activation of early growth response gene-1, which induces the
      transcription of PDGF-BB and TGF-beta(1), was decreased in AT(2)-Tg mice. These
      changes in AT(2)-Tg mice at 12 wk after (5/6)Nx were blocked by the AT(2)R
      antagonist PD-123319. Taken together, our findings suggest that AT(2)R-mediated
      signaling may protect from glomerular injuries induced by (5/6)Nx and that
      overexpression of AT(2)R may serve as a potential therapeutic strategy for
      glomerular disorders.

PMID- 14583438
TI  - Aldosterone enhances renin gene expression in juxtaglomerular cells.
AB  - The secretion and synthesis of renin as the key regulator of the renin
      angiotensin-aldosterone system are directly controlled by ANG II in the sense of
      a negative feedback. Because we found that renal afferent arterioles including
      the juxtaglomerular portion express the mineralocorticoid receptor, we aimed to
      characterize a possible direct effect of aldosterone on renin synthesis and renin
      secretion at the level of renal juxtaglomerular cells. Aldosterone (100 nM)
      clearly enhanced renin mRNA levels in primary cultures of mouse juxtaglomerular
      cells prestimulated with isoproterenol (100 nM) but had no effect on the
      exocytosis of stored renin. Similarly, in the mouse juxtaglomerular cell line
      As4.1, aldosterone time and concentration dependently increased renin mRNA
      abundance and prorenin secretion up to 2.5-fold. Moreover, aldosterone
      potentiated cAMP-induced renin gene expression in As4.1 cells. The effect of
      aldosterone was inhibited by spironolactone and was mimicked by corticosteroid
      hormones but not by sex steroids. Aldosterone had no influence on basal renin
      promoter activity but increased the renin mRNA half-life about threefold. In
      summary, these data suggest that aldosterone exerts a direct positive effect on
      renin gene expression at the cellular level probably by stabilizing renin mRNA.

PMID- 14583439
TI  - Forearm vascular control during acute hyperglycemia in healthy humans.
AB  - The vascular endothelium is a site of pathological changes in patients with
      diabetes mellitus that may be related to severe chronic hyperglycemia. However,
      it is unclear whether transient hyperglycemia alters vascular function in an
      otherwise healthy human forearm. To test the hypothesis that acute, moderate
      hyperglycemia impairs endothelium-dependent forearm vasodilation, we measured
      vasodilator responses in 25 healthy volunteers (11 F, 14 M) assigned to one of
      three protocols. In protocol 1, glucose was varied to mimic a postprandial
      pattern (i.e., peak glucose approximately 11.1 mmol/l) commonly observed in
      individuals with impaired glucose tolerance. Protocol 2 involved 6 h of mild
      hyperglycemia (approximately 7 mmol/l). Protocol 3 involved 6 h of euglycemia.
      Glucose concentration was maintained with a variable systemic glucose infusion.
      Insulin concentrations were maintained at approximately 65 pmol/l by means of a
      somatostatin and "basal" insulin infusion. Glucagon and growth hormone were
      replaced at basal concentrations. Forearm blood flow (FBF) was calculated from
      Doppler ultrasound measurements at the brachial artery. In each protocol, FBF
      dose responses to intrabrachial acetylcholine (ACh) and sodium nitroprusside
      (NTP) were assessed at baseline and at 60, 180, and 360 min of glucose infusion.
      Peak endothelium-dependent vasodilator responses to ACh were not diminished by
      hyperglycemia in any trial. For example, peak responses to ACh during protocol 2
      were 307 +/- 47 ml/min at euglycemic baseline and 325 +/- 52, 353 +/- 65, and 370
      +/- 70 ml/min during three subsequent hyperglycemic trials (P = 0.46). Peak
      endothelium-independent responses to NTP infusion were also unaffected. We
      conclude that acute, moderate hyperglycemia does not cause short-term impairment
      of endothelial function in the healthy human forearm.

PMID- 14583440
TI  - Amino acid ingestion improves muscle protein synthesis in the young and elderly.
AB  - We recently demonstrated that muscle protein synthesis was stimulated to a
      similar extent in young and elderly subjects during a 3-h amino acid infusion. We
      sought to determine if a more practical bolus oral ingestion would also produce a
      similar response in young (34 +/- 4 yr) and elderly (67 +/- 2 yr) individuals.
      Arteriovenous blood samples and muscle biopsies were obtained during a primed
      (2.0 micromol/kg) constant infusion (0.05 micromol.kg(-1).min(-1)) of L-[ring
      2H5]phenylalanine. Muscle protein kinetics and mixed muscle fractional synthetic
      rate (FSR) were calculated before and after the bolus ingestion of 15 g of
      essential amino acids (EAA) in young (n = 6) and elderly (n = 7) subjects. After
      EAA ingestion, the rate of increase in femoral artery phenylalanine concentration
      was slower in elderly subjects but remained elevated for a longer period. EAA
      ingestion increased FSR in both age groups by approximately 0.04%/h (P < 0.05).
      However, muscle intracellular (IC) phenylalanine concentration remained
      significantly higher in elderly subjects at the completion of the study (young:
      115.6 +/- 5.4 nmol/ml; elderly: 150.2 +/- 19.4 nmol/ml). Correction for the free
      phenylalanine retained in the muscle IC pool resulted in similar net
      phenylalanine uptake values in the young and elderly. EAA ingestion increased
      plasma insulin levels in young (6.1 +/- 1.2 to 21.3 +/- 3.1 microIU/ml) but not
      in elderly subjects (3.0 +/- 0.6 to 4.3 +/- 0.4 microIU/ml). Despite differences
      in the time course of plasma phenylalanine kinetics and a greater residual IC
      phenylalanine concentration, amino acid supplementation acutely stimulated muscle
      protein synthesis in both young and elderly individuals.

PMID- 14583441
TI  - Glucocorticoid-related genetic susceptibility for Alzheimer's disease.
AB  - Because glucocorticoid excess increases neuronal vulnerability, genetic
      variations in the glucocorticoid system may be related to the risk for
      Alzheimer's disease (AD). We analyzed single-nucleotide polymorphisms in 10
      glucocorticoid-related genes in a population of 814 AD patients and unrelated
      control subjects. Set-association analysis revealed that a rare haplotype in the
      5' regulatory region of the gene encoding 11beta-hydroxysteroid dehydrogenase
      type 1 (HSD11B1) was associated with a 6-fold increased risk for sporadic AD.
      Results of a reporter-gene assay indicated that the rare risk-associated
      haplotype altered HSD11B1 transcription. HSD11B1 controls tissue levels of
      biologically active glucocorticoids and thereby influences neuronal
      vulnerability. Our results indicate that a functional variation in the
      glucocorticoid system increases the risk for AD, which may have important
      implications for the diagnosis and treatment of this disease.

PMID- 14583442
TI  - Parent-of-origin effects on handedness and schizophrenia susceptibility on
      chromosome 2p12-q11.
AB  - Schizophrenia and non-right-handedness are moderately associated, and both traits
      are often accompanied by abnormalities of asymmetrical brain morphology or
      function. We have found linkage previously of chromosome 2p12-q11 to a
      quantitative measure of handedness, and we have also found linkage of
      schizophrenia/schizoaffective disorder to this same chromosomal region in a
      separate study. Now, we have found that in one of our samples (191 reading
      disabled sibling pairs), the relative hand skill of siblings was correlated more
      strongly with paternal than maternal relative hand skill. This led us to re
      analyse 2p12-q11 under parent-of-origin linkage models. We found linkage of
      relative hand skill in the RD siblings to 2p12-q11 with P=0.0000037 for paternal
      identity-by-descent sharing, whereas the maternally inherited locus was not
      linked to the trait (P>0.2). Similarly, in affected-sib-pair analysis of our
      schizophrenia dataset (241 sibling pairs), we found linkage to schizophrenia for
      paternal sharing with LOD=4.72, P=0.0000016, within 3 cM of the peak linkage to
      relative hand skill. Maternal linkage across the region was weak or non
      significant. These similar paternal-specific linkages suggest that the causative
      genetic effects on 2p12-q11 are related. The linkages may be due to a single
      maternally imprinted influence on lateralized brain development that contains
      common functional polymorphisms.

PMID- 14583443
TI  - Complement factor H mutations and gene polymorphisms in haemolytic uraemic
      syndrome: the C-257T, the A2089G and the G2881T polymorphisms are strongly
      associated with the disease.
AB  - Mutations in complement factor H (HF1) gene have been reported in non-Shiga toxin
      associated and diarrhoea-negative haemolytic uraemic syndrome (D-HUS). We
      analysed the complete HF1 in 101 patients with HUS, in 32 with thrombotic
      thrombocytopenic purpura (TTP) and in 106 controls to evaluate the frequency of
      HF1 mutations, the clinical outcome in mutation and non-mutation carriers and the
      role of HF1 polymorphisms in the predisposition to HUS. We found 17 HF1 mutations
      (16 heterozygous, one homozygous) in 33 HUS patients. Thirteen mutations were
      located in exons XXII and XXIII. No TTP patient carried HF1 mutations. The
      disease manifested earlier and the mortality rate was higher in mutation carriers
      than in non-carriers. Kidney transplants invariably failed for disease
      recurrences in patients with HF1 mutations, while in non-mutated patients half of
      the grafts were functioning after 1 year. Three HF1 polymorphic variants were
      strongly associated with D-HUS: -257T (promoter region), 2089G (exonXIV, silent)
      and 2881T (963Asp, SCR16). The association was stronger in patients without HF1
      mutations. Two or three disease-associated variants led to a higher risk of HUS
      than a single one. Analysis of available relatives of mutated patients revealed a
      penetrance of 50%. In 5/9 families the proband inherited the mutation from one
      parent and two disease-associated variants from the other, while unaffected
      carriers inherited the protective variants. In conclusion HF1 mutations are
      frequent in patients with D-HUS (24%). Common polymorphisms of HF1 may contribute
      to D-HUS manifestation in subjects with and without HF1 mutations.

PMID- 14583444
TI  - Molecular interaction of connexin 30.3 and connexin 31 suggests a dominant
      negative mechanism associated with erythrokeratodermia variabilis.
AB  - Connexins are homologous four-transmembrane-domain proteins and major components
      of gap junctions. We recently identified mutations in either GJB3 or GJB4 genes,
      encoding respectively connexin 31 (Cx31) or 30.3 (Cx30.3), as causally involved
      in erythrokeratodermia variabilis (EKV), a mostly autosomal dominant disorder of
      keratinization. Despite slight differences, phenotypes of EKV Mendes Da Costa
      (Cx31) and EKV Cram-Mevorah (Cx30.3) show major clinical overlap and both Cx30.3
      and Cx31 are expressed in the upper epidermal layers. These similarities
      suggested to us that Cx30.3 and Cx31 may interact at a molecular level. Indeed,
      expression of wild-type Cx30.3 in HeLa cell resulted only in minor amounts of
      protein addressed to the plasma membrane. Mutant Cx30.3 was hardly detectable and
      disturbed intercellular coupling. In sharp contrast, co-expression of both wild
      type proteins led to a gigantic increase of stabilized heteromeric gap junctions.
      Furthermore, co-expressed wild-type Cx30.3 and Cx31 coprecipitate, which
      demonstrates a physical interaction. Inhibitor experiments revealed that this
      interaction begins in the endoplasmic reticulum. These results not only provide
      new insights into epidermal connexin synthesis and polymerization, but also allow
      a novel molecular explanation for the similarity of EKV phenotypes.

PMID- 14583445
TI  - Functional interaction between BMPR-II and Tctex-1, a light chain of Dynein, is
      isoform-specific and disrupted by mutations underlying primary pulmonary
      hypertension.
AB  - Diverse heterozygous mutations of bone morphogenetic receptor type II (BMPR-II)
      underlie the inherited form of the vascular disorder primary pulmonary
      hypertension (PPH). As yet, the molecular detail of how such defects contribute
      to the pathogenesis of PPH remains unclear. BMPR-II is a member of the
      transforming growth factor-beta cell signalling superfamily. Ligand binding
      induces cell surface receptor complex formation and activates a cascade of
      phosphorylation events of intracellular intermediaries termed Smads, which
      initiate transcriptional regulation. Some 30% of PPH-causing mutations localize
      to exon 12, which may be spliced out forming an isoform depleted of the unusually
      long BMPR-II cytoplasmic tail. To further elucidate the consequences of BMPR2
      mutation, we sought to characterize aspects of the cytoplasmic domain function by
      seeking intracellular binding partners. We now report that Tctex-1, a light chain
      of the motor complex dynein, interacts with the cytoplasmic domain of BMPR-II and
      demonstrate that Tctex-1 is phosphorylated by BMPR-II, a function disrupted by
      PPH disease causing mutations within exon 12. Finally we show that BMPR-II and
      Tctex-1 co-localize to endothelium and smooth muscle within the media of
      pulmonary arterioles, key sites of vascular remodelling in PPH. Taken together,
      these data demonstrate a discrete function for the cytoplasmic domain of BMPR-II
      and justify further investigation of whether the interaction with and
      phosphorylation of Tctex-1 contributes to the pathogenesis of PPH.

PMID- 14583447
TI  - Role of caveolae and lipid rafts in cancer: workshop summary and future needs.

PMID- 14583446
TI  - Mouse model of N-acetylgalactosamine-6-sulfate sulfatase deficiency (Galns-/-)
      produced by targeted disruption of the gene defective in Morquio A disease.
AB  - Mucopolysaccharidosis IVA is an autosomal recessive disorder caused by a
      deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS), a lysosomal
      enzyme required for the stepwise degradation of keratan sulfate (KS) and
      chondroitin-6-sulfate (C6S). To generate a model for studies of the
      pathophysiology and of potential therapies, we disrupted exon 2 of Galns, the
      homologous murine gene. Homozygous Galns-/- mice have no detectable GALNS enzyme
      activity and show increased urinary glycosaminoglycan (GAGs) levels. These mice
      accumulate GAGs in multiple tissues including liver, kidney, spleen, heart, brain
      and bone marrow. At 2 months old, lysosomal storage is present primarily within
      reticuloendothelial cells such as Kupffer cells and cells of the sinusoidal
      lining of the spleen. Additionally, by 12 months old, vacuolar change is observed
      in the visceral epithelial cells of glomeruli and cells at the base of heart
      valves but it is not present in parenchymal cells such as hepatocytes and renal
      tubular epithelial cells. In the brain, hippocampal and neocortical neurons and
      meningeal cells had lysosomal storage. KS and C6S were more abundant in the
      cytoplasm of corneal epithelial cells of Galns-/- mice compared with wild-type
      mice by immunohistochemistry. Radiographs revealed no change in the skeletal
      bones of mice up to 12 months old. Thus, targeted disruption of the murine Galns
      gene has produced a murine model, which shows visceral storage of GAGs but lacks
      the skeletal features. The complete absence of GALNS in mutant mice makes them
      useful for studies of pharmacokinetics and tissue targeting of recombinant GALNS
      designed for enzyme replacement.

PMID- 14583448
TI  - A tumor-suppressive role for trypsin in human cancer progression.
AB  - Trypsin is a serine protease family member with a potential role in cancer
      invasion. We investigated trypsinogen expression at the RNA level in 49
      esophageal squamous cell carcinomas (ESCCs) and 72 gastric adenocarcinomas.
      Almost all primary ESCC tissues (95%) showed reduced expression, and 9 of 13 ESCC
      cell lines were silenced for trypsinogen expression. Absent expression correlated
      with promoter hypermethylation of trypsinogen-4 by bisulfite DNA sequence.
      Moreover, we detected promoter hypermethylation in 50% of primary ESCCs by
      methylation-specific PCR. A subset of gastric adenocarcinomas (71%) also showed
      reduced trypsinogen accompanied by reduction in PAR2, a G protein activated by
      trypsin, and a propensity to penetrate beyond the gastric wall (P = 0.001). Our
      results support the notion that trypsin plays a tumor-suppressive role in human
      carcinoma.

PMID- 14583449
TI  - p53-mediated repression of DNA methyltransferase 1 expression by specific DNA
      binding.
AB  - Cytosine methylation patterns in genomic DNA are significantly altered in cancer,
      and de novo CpG island methylation has been implicated in tumor suppressor gene
      silencing. Here we demonstrate a mechanistic link between the p53 tumor
      suppressor gene and control of epigenetic regulation by genomic methylation.
      Deletion of p53in HCT116 human colon carcinoma cells and primary mouse astrocytes
      resulted in a 6-fold increase of DNA cytosine methyltransferase 1 (Dnmt1) mRNA
      and protein, suggesting relief of p53-mediated Dnmt1repression. A p53 consensus
      binding site in exon 1 of the human Dnmt1gene bound recombinant p53 in vitro and
      endogenous p53 in vivo in the absence of stimuli that activate p53, implying that
      p53 controls Dnmt1transcription through direct DNA binding. Interestingly,
      ionizing radiation or etoposide, both of which stabilize and activate p53,
      diminished p53 binding in chromatin immunoprecipitation assays, concomitant with
      a 5-fold increase in Dnmt1 levels. Our findings suggest that activation of p53
      reduces binding and relieves transcriptional repression of the Dnmt1gene, whereas
      loss of p53, a frequent, early event in tumorigenesis, may significantly
      contribute to aberrant genomic methylation.

PMID- 14583450
TI  - The human ribonucleotide reductase subunit hRRM2 complements p53R2 in response to
      UV-induced DNA repair in cells with mutant p53.
AB  - Ribonucleotide reductase (RR) is responsible for the de novo conversion of the
      ribonucleoside diphosphates to deoxyribonucleoside diphosphates, which are
      essential for DNA synthesis and repair. RR consists of two subunits, hRRM1 and
      hRRM2. p53R2 is a new RR family member. Because the majority of human tumors
      possess mutant p53, it is important to know the molecular mechanism by which
      mutant p53 regulates RR and to what extent. In this study, we investigated the
      expression and function of p53R2 and hRRM2 after UV treatment in human prostate
      cancer PC3 cells, which possess mutant p53 with a truncated COOH-terminal, and in
      human oropharyngeal cancer KB cells, which possess wild-type p53. p53R2 (analyzed
      by Western blot and standardized relative to Coomassie Blue-stained band) was
      down-regulated in PC3 cells and up-regulated in KB cells after UV exposure. In
      contrast, hRRM2 was up-regulated by UV in both PC3 cells and KB cells. hRRM2 and
      p53R2 mRNA levels were assessed by Northern blot, and the results paralleled that
      of the Western blot. Coimmunoprecipitation assays using agarose-conjugated goat
      antihuman RRM1 antibody confirmed that the p53R2 binding to hRRM1 decreased in
      PC3 cells but increased in KB cells after UV treatment. hRRM2 binding to hRRM1
      increased in both cell lines under the same conditions. These results suggest
      that PC3 cells are deficient in both transcription of p53R2 and binding to hRRM1
      in response to UV irradiation. Confocal microscopy further confirmed that these
      findings were not due to translocation of hRRM2 and p53R2 from the cytoplasm to
      the nucleus. RR activity was measured following UV treatment and shown to
      increase in PC3 cells. It was unchanged in proportional of KB cells. The RR
      activity is consistent with the expression of hRRM2 seen in the Western blots.
      Thus, we hypothesize that hRRM2 complements p53R2 to form RR holoenzyme and
      maintain RR activity in PC3 cells after UV treatment. To further confirm this
      hypothesis, we examined the effect of RRM2 inhibitors on cells exposed to UV. In
      PC3 cells, hydroxyurea inhibited hRRM2 and resulted in increased sensitivity to
      UV irradiation. We also examined the effect of UV treatment on the colony-forming
      ability of cells transfected with hRRM2 as well as p53R2 sense or antisense
      expression vectors. Expression of antisense hRRM2 in PC3 cells led to decreased
      hRRM2 expression and resulted in greater sensitivity to UV than observed in wild
      type PC3 cells. Taken together, we conclude that UV-induced activation of p53R2
      transcription and binding of p53R2 to hRRM1 to form RR holoenzyme are impaired in
      the p53-mutant cell line PC3.

PMID- 14583452
TI  - Protection from doxorubicin-induced cardiac toxicity in mice with a null allele
      of carbonyl reductase 1.
AB  - Doxorubicin is a highly effective antineoplastic agent, but it can produce the
      serious side effects of acute cardiac injury and chronic congestive heart
      failure. Carbonyl reductase (CBR) has been implicated in the development of
      doxorubicin-induced cardiotoxicity. To test whether a decrease in CBR levels was
      protective against doxorubicin toxicity, we created a null allele of the Cbr1
      gene. Mice with one functional copy of the gene (Cbr1 +/-) were healthy and
      grossly normal despite having decreased levels of Cbr1 transcript and protein.
      Control and Cbr1 +/- mice were administered doxorubicin at 20 mg/kg i.p. Cbr1 +/-
      mice showed decreased circulating levels of the cardiotoxic metabolite,
      doxorubicinol, after administration. Within 2 weeks, 91% of wild-type mice were
      severely affected (n = 11) compared with 18% of Cbr1 +/- mice (n = 11).
      Echocardiography and histological analysis showed that Cbr1 +/- mice were
      protected from gross and cellular level pathologies associated with doxorubicin
      treatment. Demonstration that inhibition of carbonyl reductase blocks the toxic
      effects on the heart has important implications for improving the use of
      doxorubicin in chemotherapy.

PMID- 14583451
TI  - Energy restriction reduces the number of advanced aberrant crypt foci and
      attenuates the expression of colonic transforming growth factor beta and
      cyclooxygenase isoforms in Zucker obese (fa/fa) rats.
AB  - Several epidemiological studies have supported the concept that high energy
      intake, obesity, and/or hyperinsulinemia are risk factors for colon cancer.
      Previously, it was shown that Zucker obese rats are more sensitive to chemically
      induced colon cancer than their lean counterparts. The present study investigated
      whether moderate (20-25%) dietary energy restriction (ER) would attenuate colon
      carcinogenesis in the Zucker obese rat model. Six-week-old Zucker obese (fa/fa)
      rats and lean (Fa/Fa) rats received s.c. injections of azoxymethane at a dose of
      10 mg/kg body weight once weekly for 2 weeks. A week later, obese rats (n = 16)
      were assigned to an ER diet (Ob-ER group), based on a low-fat AIN-93G
      semisynthetic diet. The remaining obese and lean rats (n = 16 rats/group) were
      fed the low-fat diet ad libitum (Ob group and Ln group, respectively). All rats
      were euthanized after 8 weeks, and their colons were assessed for aberrant crypt
      foci (ACF; n = 8/group) or for the expression of transforming growth factor (TGF)
      beta and cyclooxygenase (COX) isoforms at the protein and mRNA transcript levels
      (n = 8/group). Ob rats had a higher number of advanced ACF (crypt multiplicity
      >or=7) than Ln rats. Dietary ER significantly reduced the appearance of advanced
      ACF in Ob-ER rats without significantly affecting the blood insulin level or body
      weights. TGF-beta and COX isoforms were differentially expressed in the colonic
      mucosae of Ob and Ln rats. Dietary ER significantly reduced TGF-beta1/beta2 and
      COX-1/2 protein expression in obese rats. This study is the first to demonstrate
      that moderate ER attenuated TGF-beta and COX protein expression and the
      carcinogenic process in Zucker obese rats. These findings provide insights
      leading to the proposal that the mechanism(s) underlying the early events of
      colon carcinogenesis in Zucker obese rats may extend beyond the role of excessive
      body weight and hyperinsulinemia per se.

PMID- 14583453
TI  - Phytoestrogen-rich diets modulate expression of Brca1 and Brca2 tumor suppressor
      genes in mammary glands of female Wistar rats.
AB  - Phytoestrogens are natural compounds with anticancer, proliferation,
      differentiation, and chemopreventive effects, for which several mechanisms have
      been proposed. In the present study, modulation of Brca1 and Brca2 expression by
      different phytoestrogen-rich diets has been investigated in ovariectomized Wistar
      rats. Two hundred mammary glands were harvested in three independent experiments.
      Brca1 and Brca2 mRNAs were quantified by real-time quantitative reverse
      transcription-PCR, and their proteins by immunohistochemistry. The first
      experiment compared the influence of different phytoestrogens [flax-seed,
      isoflavones (IFs), or rutin]. A 10% increase in Brca1 mRNA expression was shown
      after flax-seed consumption, whereas no variation was noted for Brca2 mRNA, nor
      for Brca1 and Brca2 proteins. In the second experiment, two soy IFs sources
      (Novasoy or Soylife) were given at different concentrations to the animals. Only
      Brca2 mRNA was increased and only at high doses. Finally, the effect of IFs was
      compared with that of estradiol. An increase in mRNA for both genes was noted
      after estradiol treatment and with the highest dose of IFs. In conclusion, our
      results show that IFs, given in the diet at different doses, are able to increase
      Brca1 and Brca2 mRNA in ovariectomized female Wistar rat. However, no variation
      in Brca1 or Brca2 protein expression was demonstrated, whatever the experimental
      conditions were.

PMID- 14583454
TI  - Classification of human astrocytic gliomas on the basis of gene expression: a
      correlated group of genes with angiogenic activity emerges as a strong predictor
      of subtypes.
AB  - The development of targeted treatment strategies adapted to individual patients
      requires identification of the different tumor classes according to their biology
      and prognosis. We focus here on the molecular aspects underlying these
      differences, in terms of sets of genes that control pathogenesis of the different
      subtypes of astrocytic glioma. By performing cDNA-array analysis of 53 patient
      biopsies, comprising low-grade astrocytoma, secondary glioblastoma (respective
      recurrent high-grade tumors), and newly diagnosed primary glioblastoma, we
      demonstrate that human gliomas can be differentiated according to their gene
      expression. We found that low-grade astrocytoma have the most specific and
      similar expression profiles, whereas primary glioblastoma exhibit much larger
      variation between tumors. Secondary glioblastoma display features of both other
      groups. We identified several sets of genes with relatively highly correlated
      expression within groups that: (a). can be associated with specific biological
      functions; and (b). effectively differentiate tumor class. One prominent gene
      cluster discriminating primary versus nonprimary glioblastoma comprises mostly
      genes involved in angiogenesis, including VEGF fms-related tyrosine kinase 1 but
      also IGFBP2, that has not yet been directly linked to angiogenesis. In situ
      hybridization demonstrating coexpression of IGFBP2 and VEGF in pseudopalisading
      cells surrounding tumor necrosis provided further evidence for a possible
      involvement of IGFBP2 in angiogenesis. The separating groups of genes were found
      by the unsupervised coupled two-way clustering method, and their classification
      power was validated by a supervised construction of a nearly perfect glioma
      classifier.

PMID- 14583455
TI  - SKI activates Wnt/beta-catenin signaling in human melanoma.
AB  - Overexpression of the oncoprotein SKI correlates with the progression of human
      melanoma in vivo. SKI is known to curtail the growth inhibitory activity of tumor
      growth factor beta through the formation of repressive transcriptional complexes
      with Smad2 and Smad3 at the p21(Waf-1) promoter. Here, we show that SKI also
      stimulates growth by activating the Wnt signaling pathway. From a yeast two
      hybrid screen and immunoprecipitation studies, we identified the protein
      FHL2/DRAL as a novel SKI binding partner. FHL2, a LIM-only protein, binds beta
      catenin and can function as either a transcriptional repressor or activator of
      the Wnt signaling pathway. SKI enhanced the activation of FHL2 and/or beta
      catenin- regulated gene promoters in melanoma cells. Among the SKI targets were
      microphthalmia-associated transcription factor and Nr-CAM, two proteins
      associated with melanoma cell survival, growth, motility, and transformation.
      Transient overexpression of SKI and FHL2 in ski(-/-) melanocytes synergistically
      enhanced cell growth, and stable overexpression of SKI in a poorly clonogenic
      human melanoma cell line was sufficient to stimulate rapid proliferation,
      decreasing the number of cells in the G(1) phase of the cell cycle, and
      dramatically increasing clonogenicity, colony size and motility. Taken together,
      these results suggest that by targeting members of the tumor growth factor beta
      and beta-catenin pathways, SKI regulates crucial events required for melanoma
      growth, survival, and invasion.

PMID- 14583456
TI  - Evolutionary dynamics of mutator phenotypes in cancer: implications for
      chemotherapy.
AB  - Genetic instability is a central characteristic of cancers. However, the
      selective forces responsible for the emergence of genetic instability are not
      clear. We use mathematical models to determine the conditions under which
      selection favors instability, and when stable cells are advantageous. We take
      into account the processes of DNA damage, repair, cell cycle arrest, mutation,
      and death. We find that the rate of DNA damage can play a major role in this
      context. In particular, an increase in the rate of DNA damage can reverse the
      relative fitness of stable and unstable cells. In terms of cancer progression, we
      find the following results. If cells have intact apoptotic responses, stable
      cells prevail if the DNA hit rate is low. A high DNA hit rate can result in the
      selection of genetically unstable cells. This has implications for the induction
      of tumors by carcinogens. On the other hand, if cells are characterized by
      impaired apoptosis, we observe the opposite. Genetic instability is selected for
      if the DNA hit rate is low. A high DNA hit rate can select against instability
      and result in the persistence of stable cells. We propose that chemotherapy can
      be used to reverse the relative fitness of stable and unstable cells, such that
      unstable cells are the inferior competitors. This could result in the competitive
      exclusion of progressing cancer cells.

PMID- 14583457
TI  - Li-Fraumeni and related syndromes: correlation between tumor type, family
      structure, and TP53 genotype.
AB  - A database has been created to collect information on families carrying a germ
      line mutation in the TP53 gene and on families affected with Li-Fraumeni
      syndromes [Li-Fraumeni syndrome (LFS) and Li-Fraumeni-like syndrome (LFL)]. Data
      from the published literature have been included. The database is available
      online at http://www.iarc.fr/p53, as part of the IARC TP53 Database. The analysis
      of the 265 families/individuals that have been included thus far has revealed
      several new findings. In classical LFS families with a germ-line TP53 mutation
      (83 families), the mean age of onset of breast cancer was significantly lower
      than in LFS families (16 families) without a TP53 mutation (34.6 versus 42.5
      years; P = 0.0035). In individuals with a TP53 mutation, a correlation between
      the genotype and phenotype was found. Brain tumors were associated with missense
      TP53 mutations located in the DNA-binding loop that contact the minor groove of
      DNA (P = 0.01), whereas adrenal gland carcinomas were associated with missense
      mutations located in the loops opposing the protein-DNA contact surface (P =
      0.003). Finally, mutations likely to result in a null phenotype (absence of the
      protein or loss of function) were associated with earlier onset brain tumors (P =
      0.004). These observations have clinical implications for genetic testing and
      tumor surveillance in LFS/LFL families.

PMID- 14583458
TI  - Inhibition of angiogenesis and vascular leakiness by angiopoietin-related protein
      4.
AB  - Angiopoietins and angiopoietin-related proteins (ARPs) have been shown to
      regulate angiogenesis, a process essential for various neovascular diseases
      including tumors. Here, we identify ARP4/fasting-induced adipose
      factor/peroxisome proliferator-activated receptor gamma angiopoietin-related as a
      novel antiangiogenic modulatory factor. We hypothesized that ARP4 may regulate
      angiogenesis. In vitro experiments using purified recombinant ARP4 protein
      revealed that ARP4 markedly inhibited the proliferation, chemotaxis, and tubule
      formation of endothelial cells. Moreover, using corneal neovascularization and
      Miles permeability assays, we found that both vascular endothelial growth factor
      induced in vivo angiogenesis and vascular leakiness were significantly inhibited
      by the addition of ARP4. Finally, we found remarkable suppression of tumor growth
      within the dermal layer associated with decreased numbers of invading blood
      vessels in transgenic mice that express ARP4 in the skin driven by the
      keratinocyte promoter. These findings demonstrate that ARP4 functions as a novel
      antiangiogenic modulatory factor and indicate a potential therapeutic effect of
      ARP4 in neoplastic diseases.

PMID- 14583459
TI  - The proline-rich acidic protein is epigenetically regulated and inhibits growth
      of cancer cell lines.
AB  - The proline-rich acidic protein (PRAP) gene was found previously to be expressed
      in the epithelial cells of the mouse and rat gastrointestinal tracts, and
      pregnant mouse uterus. This article describes the isolation, distribution, and
      functional characterization of the human homologue. PRAP was abundantly expressed
      in the epithelial cells of the human liver, kidney, gastrointestinal tract, and
      cervix. PRAP expression was significantly down-regulated in hepatocellular
      carcinoma and right colon adenocarcinoma compared with the respective adjacent
      normal tissues. Treatment of the cells with butyrate, trichostatin A, and 5'-aza
      2' deoxycytidine caused increases in PRAP gene expression of up to 30-fold,
      suggesting that the gene is suppressed through epigenetic mechanisms involving
      histone deacetylation and methylation. To determine the significance of PRAP
      expression in cancer cells, we cloned PRAP and its two major splice variants from
      human colon and liver, and overexpressed it in HeLa, HT29, and HepG2 cells. PRAP
      caused cell growth inhibition in the cancer cell lines in transient transfection
      assays, colony formation assays, and in the growth rates of stable clones. The
      data suggest that PRAP and its variants may play an important role in maintaining
      normal growth homeostasis in epithelial cells. The epigenetic suppression of PRAP
      expression in cancer may cause growth dysregulation, a hallmark of the
      carcinogenic process.

PMID- 14583460
TI  - Critical elements of the immunoglobulin heavy chain gene enhancers for
      deregulated expression of bcl-2.
AB  - Translocation of the bcl-2 gene to the immunoglobulin heavy chain gene is the
      most common alteration in follicular lymphoma. The result is the deregulated
      expression of bcl-2 and increased resistance to cell death. Regulation of the
      immunoglobulin heavy chain gene is controlled in part by four DNase I
      hypersensitive regions located 3' of the gene. Here, we show that these four
      enhancer regions also contribute to bcl-2 up-regulation in t(14;18) cells. The
      enhancers are able to individually or in combination activate bcl-2 promoter
      activity. The HS4 enhancer region was found to impart the largest positive effect
      on the bcl-2 promoter, activating it by 6-fold, whereas addition of the HS1,2
      region with HS4 increased promoter activity by approximately 9-fold. Nuclear
      factor kappaB binding sites were shown to be primarily responsible for the
      positive activity contributed by the HS1,2 and HS4 regions, and we observed the
      in vivo interaction of these factors with the human immunoglobulin heavy chain
      gene enhancer regions in t(14;18) cells. In addition, two Sp1 binding sites in
      HS4 were also found to positively influence bcl-2 activity, and Sp1 was observed
      to interact with the human HS4 enhancer in vivo. These results suggest that the
      interactions of the nuclear factor kappaB and Sp1 transcription factors with the
      immunoglobulin heavy chain enhancer region are important for bcl-2 deregulation
      in t(14;18) cells.

PMID- 14583461
TI  - Loss of p53 has site-specific effects on histone H3 modification, including
      serine 10 phosphorylation important for maintenance of ploidy.
AB  - Histone modification enables the ordered regulation of DNA-related processes.
      Here, we ask if p53, which interacts with histone modifying complexes in vivo,
      influences histone H3 modification. For this purpose, we compared isogenic clones
      of human p53+/+ and p53-/- cells in which it is reasonable to attribute any
      observed differences in histone modification to p53-related effects. Cell growth
      and cell cycle analyses indicated equivalent proliferation rates for the p53+/+
      and p53-/- cell clones. Modification of histone H3 was determined under normal
      cell growth conditions and also after UV irradiation and/or treatment with
      trichostatin A (TSA) or nicotinamide (two inhibitors of histone deacetylation).
      Site-specific histone H3 modifications were determined by immunoblotting. We
      provide evidence that p53 influences histone H3 acetylation at lysine 9 (K9) and
      K14, whereas acetylation of K18 appears to be p53 independent. The most striking
      p53-related effects are at K9, which is underacetylated in p53-/- cells under
      normal conditions of growth but which shows a dramatic increase in acetylation
      after combined treatment with UV plus TSA. Conversely, phosphorylation of serine
      10 (S10P) is elevated in p53-/- cells and reduced after UV plus TSA treatment.
      Similar reciprocity between K9Ac and S10P was not evident in p53+/+ cells.
      Abnormal S10P in p53-/- cells was also observed under completely different
      experimental conditions where cells were treated with nocodazole to induce G(2)-M
      arrest and elevation of S10P (which is linked with G(2)-M of the cell cycle). On
      removal of nocodazole, the p53+/+ cells exhibited rapid reduction in S10P levels
      and cell cycle recovery. In contrast, the p53-/- cells retained elevated S10P
      levels and failed to show normal cell cycle recovery. Phosphorylation of S10 is
      known to be linked with the initiation of chromosome condensation in G(2) and is
      also important for proper chromosome segregation at mitosis. Our results indicate
      that loss of p53, directly or indirectly, perturbs the normal regulation of S10
      phosphorylation. We suggest that this effect may contribute toward the
      development of abnormal chromosomes and aneuploidy in p53-deficient cancers.

PMID- 14583462
TI  - Induction of C-anaphase and diplochromosome through dysregulation of spindle
      assembly checkpoint by sodium arsenite in human fibroblasts.
AB  - Cytogenetic alterations induced by arsenite are associated with its carcinogenic
      activity. Cytogenetic analysis revealed first that arsenite induced c-anaphases
      in a time- and dose-dependent manner in human fibroblasts (HFW). With additional
      incubation of arsenite-arrested mitotic cells in drug-free medium for 0-48 h,
      approximately 35% exited from mitosis without cell division. This was confirmed
      by the appearance of tetraploid metaphase, mainly diplochromosomes, in the
      subsequent cell division. Treatment of HFW cells with both nocodazole, a known
      agent of microtubular depolymerization, and Taxol, which induces tubulin
      polymerization and inhibits disassembly of microtubules, resulted in remarkable
      mitotic arrest but induced only negligible c-anaphase, tetraploidy, and
      diplochromosomes. Staurosporine, a kinase inhibitor that could effectively reduce
      arsenite-induced c-anaphase, could also decrease the development of
      diplochromosomes in the subsequent cell division cycle. These results imply that
      arsenite-induced c-anaphases mainly exited from mitosis without cell division and
      became tetraploid in the subsequent cell cycle. Antitubulin immunofluorescent
      staining confirmed no formation of bipolar spindles in nocodazole-arrested
      mitotic HFW cells, whereas in arsenite-arrested mitotic cells bipolar spindles
      were present but distorted in appearance and apparently dysfunctional. Mitotic
      arrest deficient 2 (Mad2) signal was, as expected, clearly visible at centromeres
      of nocodazole-arrested mitotic cells. However, the Mad2 signal at centrosomes
      became insignificant in either arsenite-arrested or nocodazole/arsenite-arrested
      mitotic cells. In addition, the association of Mad2 with the APC/C(cdc20) complex
      and the accumulation of Pds1, an anaphase inhibitor, were remarkably reduced in
      arsenite-arrested mitotic cells as compared with nocodazole-arrested mitotic
      cells. These results support the observation that nocodazole can inhibit spindle
      formation and, hence, activate spindle assembly checkpoint to arrest cells at
      metaphase. In contrast, the dysfunctional bipolar spindles in arsenite-arrested
      mitotic cells could not effectively activate spindle assembly checkpoint and,
      hence, resulted in formation of c-anaphase and diplochromosomes in the subsequent
      cell division.

PMID- 14583463
TI  - Fluorescence imaging of multiple myeloma cells in a clinically relevant SCID/NOD
      in vivo model: biologic and clinical implications.
AB  - The in vivo preclinical testing of investigational therapies for multiple myeloma
      (MM) is hampered by the fact that models generated to recapitulate the
      development of diffuse skeletal lesions after i.v. injections of tumor cells do
      not allow for ready detection of the exact site(s) of lesions or for
      comprehensive monitoring of their progression. We therefore developed an in vivo
      MM model in severe combined immunodeficient/nonobese diabetic mice in which
      diffuse MM lesions developed after tail vein i.v. injection of human RPMI-8226/S
      MM cells stably transfected with a construct for green fluorescent protein (GFP).
      Using whole-body real-time fluorescence imaging to detect autofluorescent GFP(+)
      MM cells (and confirming the sensitivity and specificity of these findings both
      histologically and by flow cytometric detection of GFP(+) cells), we serially
      monitored, in a cohort of 75 mice, the development and progression of MM tumors.
      Their anatomical distribution and pathophysiological manifestations were
      consistent with the clinical course of MM in human patients, i.e., hallmarked by
      major involvement of the axial skeleton (e.g., spine, skull, and pelvis) and
      frequent development of paralysis secondary to spinal lesions without significant
      tumor spread to lungs, liver, spleen, or kidney. This model both recapitulates
      the diffuse bone disease of human MM and allows for serial whole-body
      visualization of its spatiotemporal progression. It therefore provides a valuable
      in vivo system to elucidate the molecular mechanisms underlying the marked
      osteotropism of MM, particularly for the axial skeleton, and for assessment of in
      vivo activity of novel anti-MM therapeutics.

PMID- 14583464
TI  - Adenoviral-mediated expression of a kinase-dead mutant of Akt induces apoptosis
      selectively in tumor cells and suppresses tumor growth in mice.
AB  - Akt/protein kinase B is a serine/threonine kinase that plays a critical role in
      cell survival signaling, and its activation has been linked to tumorigenesis in
      several human cancers. Up-regulation of Akt, as well as its upstream regulator
      phosphatidylinositol 3-kinase, has been found in many tumors, and the negative
      regulator of this pathway, mutated in multiple advanced cancers suppressor (MMAC;
      also known as phosphatase and tensin homologue deleted on chromosome 10), is a
      tumor suppressor gene. We have investigated the effects of inhibiting Akt
      signaling in tumor cells by expression of an Akt kinase-dead mutant in which the
      two regulatory phosphorylation sites have been mutated to alanines. This mutant,
      which functions in a dominant negative manner (Akt-DN), was introduced into tumor
      cells using a replication-defective adenovirus expression system. As controls we
      used adenoviruses expressing p53, MMAC, beta-galactosidase, and empty virus. We
      show that in vitro proliferation of human and mouse tumor cells expressing high
      levels of activated/phosphorylated Akt was inhibited by both Akt-DN and p53, in
      comparison with control viruses expressing beta-galactosidase. Similarly, Akt-DN
      mutant expression led to selective induction of apoptosis in tumor cells
      expressing activated Akt. On the other hand, Akt-DN expression had minimal effect
      in normal and tumor cells expressing low levels of activated Akt. Expression of
      MMAC induced selective apoptosis in tumor cell lines in which MMAC is inactivated
      but not in tumor cells expressing wild-type levels of MMAC. In addition, the
      growth of tumor cells in a mouse model was also significantly inhibited by
      intratumoral injection of Akt-DN virus. These studies validate the usefulness of
      targeting Akt for new drug discovery efforts and suggest that inhibition of Akt
      may have a selective antitumor effect.

PMID- 14583465
TI  - Acquired tolerance of hepatocellular carcinoma cells to selenium deficiency: a
      selective survival mechanism?
AB  - Selenium is essential to human health, and its deficiency is associated with
      different diseases including liver necrosis. Selenium is protective against viral
      hepatitis and hepatocellular carcinoma (HCC). The underlying molecular mechanisms
      of selenium effects are not well known. In this study, in vitro response of HCC
      derived cell lines to selenium deficiency is examined alone or in conjunction
      with Vitamin E and copper/zinc. Here, we show that in vitro selenium deficiency
      in a subset of HCC-derived cell lines causes oxidative stress and cytochrome c
      release with subsequent cell death by apoptosis. The oxidative stress and
      consequent cell death induced by selenium deficiency on these cells are reverted
      by the antioxidant effect of Vitamin E. However, most HCC cell lines (10 of 13)
      tolerate selenium deficiency. Consequently, they escape apoptosis. Moreover, nine
      of these tolerant cell lines have integrated hepatitis B Virus (HBV) DNA in their
      genomes, and some display p53-249 mutation, indicating past exposure to HBV or
      aflatoxins, established factors for oxidative stress and cancer risk in liver. An
      HBV-transfected clone (2.2.15) of the sensitive HepG2 cell line has gained
      tolerance to selenium deficiency. Our findings indicate that selenium deficiency
      induces apoptosis in some "hepatocyte-like" cells. However, most HCC cells,
      particularly HBV-related ones, tolerate selenium deficiency and escape its deadly
      consequences. Thus, as demonstrated by the gain of survival capacity of apoptosis
      sensitive cell lines with Vitamin E, such malignant cells have acquired a
      selective survival advantage that is prominent under selenium-deficient and
      oxidative-stress conditions.

PMID- 14583466
TI  - Functional proteomic analysis of melanoma progression.
AB  - Functional proteomics provides a powerful approach to screen for alterations in
      protein expression and posttranslational modifications under conditions of human
      disease. In this study, we use protein screening to examine markers of melanoma
      progression, by profiling melanocyte versus melanoma cell lines using two
      dimensional electrophoresis and mass spectrometry. Eight candidate markers were
      identified as differentially regulated in transformed cells. In particular,
      hepatoma-derived growth factor (HDGF) and nucleophosmin B23 were strongly
      correlated with melanoma. Nucleophosmin B23 is a nucleolar and centrosome
      associated protein, which has been implicated as a target for cyclin E/cyclin
      dependent kinase 2 (CDK2) in modulating centrosome duplication and cell cycle
      control. Western blotting of one-dimensional and two-dimensional gels showed that
      the form of nucleophosmin B23 that is up-regulated in melanoma represents a
      posttranslationally modified form, most likely reflecting enhanced
      phosphorylation in the tumor-derived cells. In contrast, Western analysis of HDGF
      demonstrated increased expression of all forms in melanoma cell lines compared
      with melanocytes. Immunohistochemical analysis of human tissue biopsies showed
      strong expression of HDGF in early and late stage melanomas and low expression in
      melanocytes and nontumorigenic nevi. Interestingly, biopsies of nevi showed a
      graded effect in which HDGF immunoreactivity was reduced in nevoid nests
      penetrating deep into the dermis compared with nests at the epidermal-dermal
      junction, suggesting that HDGF expression in nevi is dependent on epidermal cell
      interactions. In contrast, biopsies of melanoma showed strong expression of HDGF
      throughout the tumor, including cells located deeply within dermis. Thus,
      expression of this antigen likely reports a reduced dependence of protein
      expression on epidermal interactions.

PMID- 14583467
TI  - Inhibition of angiotensin II activity enhanced the antitumor effect of
      cyclooxygenase-2 inhibitors via insulin-like growth factor I receptor pathway.
AB  - Prostaglandin (PG) E(2), a cyclooxygenase (COX) product, and angiotensin II are
      endogenous and have physiological roles in the body. On the other hand, an
      inducible isoform of COX (COX-2), insulin-like growth factor (IGF) II, and IGF-I
      receptor (IGF-IR) are up-regulated in colon carcinoma and might have crucial
      roles in tumor growth and invasion. The aim of the present study was to
      investigate the effects of COX-2 inhibitor and drugs blocking the biological
      activities of angiotensin II [angiotensin-converting enzyme (ACE) inhibitors or
      angiotensin II receptor blockers (ARBs)] on IGF-IR expression and tumor growth in
      vivo. We also investigated the effects of PGE(2), a major COX-2 product, in
      cancer cells and the effects of angiotensin II on IGF-IR expression and the
      underlying mechanism of action. In in vivo studies, tumor growth and IGF-IR
      expression were investigated in Colon 26 cells inoculated into BALB/c mice. In in
      vitro studies, the effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on
      IGF-IR expression were analyzed in three colon cancer cell lines (Colon 26, HCA
      7, and LS174T). IGF-II-induced cell growth and invasion were analyzed in Colon 26
      cells in the presence and absence of NSAIDs (indomethacin and celecoxib) and
      angiotensin II. Celecoxib at the lowest effective dose for suppression of PG
      production (3 mg/kg) or an ACE inhibitor/ARB alone did not have a significant
      effect as compared with controls, although a high dose of celecoxib (>20 mg/kg)
      suppressed tumor growth. On the other hand, combination therapy with these two
      categories of drugs significantly reduced tumor growth in vivo. Treatment with
      both celecoxib and an ACE inhibitor/ARB decreased IGF-IR expression levels in
      inoculated tumor cells. In in vitro studies, NSAIDs reduced IGF-IR expression in
      a dose-dependent manner in all three cell lines. NSAIDs also inhibited IGF-II
      stimulated growth and invasion in a dose-dependent manner. PGE(2) or angiotensin
      II treatment reversed the NSAID-induced down-regulation of IGF-IR expression,
      growth, and invasion. PGE(2) and angiotensin II induced Akt phosphorylation, and
      LY294002 or wortmannin inhibited PGE(2)- or angiotensin II-induced IGF-IR
      expression, indicating that PGE(2) and angiotensin II both regulate IGF-IR
      expression by the same Akt/phosphatidylinositol-3 pathway. Thus, combination
      therapy with NSAIDs and ACE inhibitors targeting IGF-IR might be a novel and
      potentially promising strategy for the chemoprevention of colon cancer.

PMID- 14583468
TI  - Identification of a colorectal tumor-associated antigen (COA-1) recognized by
      CD4(+) T lymphocytes.
AB  - Only a limited number of target molecules have been shown to be recognized by
      colon tumor-reactive T cells, limiting the options for the development of
      immunotherapies for patients with colon cancer. The current studies were
      undertaken in an attempt to generate tumor-reactive T cells that could be used to
      identify and characterize novel colon tumor-associated antigens. Multiple CD4(+)
      T-cell clones isolated either from tumor-infiltrating lymphocytes or peripheral
      blood mononuclear cells that were sensitized in vitro with autologous tumor cells
      from a colon cancer patient, 1869, recognized autologous tumor cells in a class
      II HLA-DR-restricted manner. One of the peripheral blood mononuclear cell clones,
      clone C111, was used to screen pools of clones that were generated from an
      autologous colon tumor cell line cDNA library. A cDNA clone that was isolated
      encoded a protein that was termed colorectal tumor-associated antigen-1 (COA-1).
      This product was recognized in the context of the two autologous HLA-DRbeta1
      alleles, HLA-DRbeta1*0402 and DRbeta1*1301. The nucleotide sequence of the COA-1
      transcript was nearly identical to multiple expressed sequence tag sequences that
      encode variants of Socius, a protein that was found recently to bind to members
      of the Rnd family of GTPases. The COA-1 gene was expressed at relatively
      comparable levels in colorectal and melanoma tumor cells, EBV-infected B cells,
      normal B cells, and cultured fibroblast cell lines. However, the gene that was
      isolated from normal cell types contained a single nucleotide substitution,
      resulting in an amino acid change near the COOH terminus of the protein. Although
      the minimal epitope recognized by CD4(+) cells was encoded by sequences that were
      upstream from this substitution, C111 T cells did not appear to recognize the
      normal gene product. Therefore, this alteration may either affect the
      localization or the processing of this gene product, which may at least in part
      be responsible for the differential recognition of tumor and normal cells.

PMID- 14583469
TI  - Transactivation of the epidermal growth factor receptor mediates cholinergic
      agonist-induced proliferation of H508 human colon cancer cells.
AB  - Some human colon cancer cell lines (e.g., H508 cells) express M3 subtype
      muscarinic receptors that are activated by cholinergic agonists. The objective of
      the present study was to determine the cellular mechanisms underlying M3
      muscarinic receptor-mediated proliferation of H508 human colon cancer cells. In
      H508 cells, but not in SNU-C4 cells that do not express muscarinic receptors,
      acetylcholine stimulated calcium-dependent phosphorylation of p44/42 mitogen
      activated protein kinase (MAPK) and p90 ribosomal S6 kinase and consequent cell
      proliferation. Atropine or inhibitors of MAPK phosphorylation blocked these
      effects. Conversely, the actions of epidermal growth factor (EGF) on H508 cells
      were neither calcium dependent nor mediated by cholinergic mechanisms. Both
      acetylcholine- and EGF-induced phosphorylation of p44/42 MAPK was abolished in
      the presence of EGF receptor (EGFR) inhibitors (AG1478 and PD168393). In Chinese
      hamster ovary cells transfected with the rat M3 muscarinic receptor, which lack
      EGFR, acetylcholine-induced MAPK phosphorylation was not altered in the presence
      of EGFR inhibitors. In H508 cells, protein kinase C inhibitors did not alter
      acetylcholine- or EGF-induced MAPK phosphorylation. Finally, inhibition of EGFR
      activation abolished acetylcholine-induced H508 cell proliferation. These data
      indicate that, in H508 human colon cancer cells, cholinergic ligand interaction
      with M3 muscarinic receptors results in transactivation of EGFR, thereby
      stimulating cellular proliferation.

PMID- 14583470
TI  - CXCR4 enhances adhesion of B16 tumor cells to endothelial cells in vitro and in
      vivo via beta(1) integrin.
AB  - The chemokine receptor, CXCR4, is expressed by human melanomas, and its ligand,
      CXCL12, is frequently produced at sites of melanoma metastasis. Herein, we
      examine CXCR4-enhanced binding of B16 murine melanoma cells to endothelial cells
      (ECs) and recombinant adhesion molecules in vitro to determine the role of tumor-
      and EC-derived adhesion molecules in tumor metastasis. By flow cytometry,
      unstimulated primary lung ECs showed constitutive expression of vascular cellular
      adhesion molecule 1 (VCAM-1), whereas skin-derived ECs did not. All B16 cell
      lines tested showed constitutive expression of alpha(4) and beta(1) integrin
      chains but showed no expression of beta(2) integrins. CXCR4-B16 arrest on VCAM
      1/immunoglobulin-coated plates and tumor necrosis factor alpha-stimulated ECs
      under physiological shear stress conditions (1.5 dynes/cm(2)) was rapid,
      resistant to shear stress of 10 dynes/cm(2), and showed no evidence of rolling
      before arrest. In vitro, CXCR4-B16 cell binding to ECs was blocked by anti
      beta(1) and anti-CXCL12 monoclonal antibodies. In vivo, metastasis of CXCR4-B16
      cells to murine lungs was strongly inhibited by anti-CXCL12 and two different
      anti-beta(1) monoclonal antibodies. Finally, CXCR4-B16 exposed to CXCL12 rapidly
      increased binding affinity for soluble VCAM-1/immunoglobulin as detected by a
      flow cytometric assay. Thus, beta(1) integrins play a critical role in CXCR4
      mediated B16 tumor cell metastasis in vivo and may be a potential target for
      inhibition of tumor metastasis, particularly to the lung.

PMID- 14583471
TI  - Direct activation of pro-matrix metalloproteinase-2 by leukolysin/membrane-type 6
      matrix metalloproteinase/matrix metalloproteinase 25 at the asn(109)-Tyr bond.
AB  - Leukolysin/membrane-type 6 matrix metalloproteinase (leukolysin/MT6-MMP), a
      glycosylphosphatidylinositol-anchored neutrophil matrix metalloproteinase, is
      also abnormally expressed in brain cancer tissues. Yet, little is known about its
      role in cancer progression. Here we show that MT6-MMP is capable of activating
      proMMP-2, an enzyme implicated in tumor invasion and metastasis. Although MT6-MMP
      is only 10% as active as MT5-MMP in mediating proMMP-2 activation, it generates a
      higher ratio of mature/intermediate forms of MMP-2 than MT5-MMP. Consistently,
      purified CAT of MT6-MMP converts proMMP-2 into mostly the mature form. Using the
      catalytically inactive mutant MMP-2EA (the E404A mutant of proMMP-2), which
      cannot autocatalytically mature from the intermediate form into the mature one,
      we show that MT6-MMP cleaves not only the known MT-MMP-processing site at Asn(66)
      Leu but also the previously unsuspected Asn(109)-Tyr to yield a fully mature
      molecule. Despite their difference in mediating proMMP-2 activation in
      transfected cells, the CAT of MT6-MMP appears to be as efficient as that of MT5
      MMP in cleaving proMMP-2EA in buffer, suggesting that its CAT is a strong proMMP
      2 activator. Indeed, the CAT of MT6-MMP can partially substitute the CAT of
      prototypical MT1-MMP in mediating proMMP-2 activation. Taken these facts
      together, we conclude that MT6-MMP may participate in tumor invasion and
      metastasis by directly converting proMMP-2 into active form.

PMID- 14583472
TI  - Constitutive activation of Stat5b contributes to carcinogenesis in vivo.
AB  - The development of more effective prevention and treatment strategies for solid
      tumors is limited by an incomplete understanding of the critical growth pathways
      that are activated in carcinogenesis. Signal transducers and activators of
      transcription (STAT) proteins have been linked to transformation and tumor
      progression. Studies to date have not elucidated clear and distinct roles for
      Stat5genes (Stat5a and Stat5b) in human epithelial cancers. We analyzed the role
      of Stat5a/b isoforms in squamous cell carcinoma of the head and neck using
      expression and activation studies in human tissues and in a xenograft model after
      selective targeting. In a xenograft model, blockade of Stat5b, but not Stat5a,
      using antisense oligonucleotides resulted in tumor growth inhibition and
      abrogation of Stat5 target genes in vivo. Blockade of the epidermal growth factor
      receptor resulted in partial abrogation of Stat5 activation, thus linking
      epidermal growth factor receptor to Stat5 in vivo. In tissues from 33 individuals
      with head and neck cancer, Stat5 activation levels were correlated with
      progression to a malignant phenotype, where increased expression and
      phosphorylation of Stat5b were detected consistently in tumors compared with
      their epithelial counterparts. Thus, constitutive activation of Stat5b
      contributes to squamous cell tumorigenesis and may serve as a therapeutic target.

PMID- 14583473
TI  - Shc proteins are strong, independent prognostic markers for both node-negative
      and node-positive primary breast cancer.
AB  - Activated Shc signaling proteins are implicated in many pathways associated with
      aggressive disease, and many breast cancer cell lines derived from highly
      aggressive tumors contain high levels of activated, tyrosine phosphorylated (PY)
      Shc (the M(r) 46000 and M(r) 52000 isoforms) relative to levels of an inhibitory
      M(r) 66000 Shc isoform. It was, therefore, hypothesized that high amounts of PY
      Shc relative to the M(r) 66000 Shc isoform would serve as a marker for aggressive
      neoplasms. Semiquantitative immunohistochemical analyses of PY-Shc and p66 Shc
      were performed on archival primary breast tumor specimens from 116 women, 17 of
      whom experienced relapse (6.1 years median follow-up of nonrelapsed patients).
      Consistent with our hypothesis, staining intensities demonstrated that increased
      amounts of PY-Shc (P = 0.01) and decreased expression of p66-Shc protein (P =
      0.028) correlated with disease recurrence. Modeled as the ratio of PY-Shc to p66
      Shc, the Shc ratio correlated strongly with nodal status (P = 0.003), tumor stage
      (P = 0.0025), and disease stage (P = 0.002) and was 2-fold higher in primary
      tumors of patients who subsequently relapsed (P < 0.001). Univariate Cox
      proportional hazards analysis of relapse-free survival demonstrated the
      prognostic value of PY-Shc (P = 0.01), p66 Shc (P = 0.04), and the Shc ratio (P =
      0.004) as continuous variables, with a hazard ratio (HR) of 10 (P = 0.007) for
      the Shc ratio. Shc ratio cut points of <0.35 and >0.65 were identified and
      independently validated to maximize negative predictive value and positive
      predictive value. Patients with low Shc ratios (n = 36) had a 0.08 HR of relapse
      (P = 0.007) compared with patients with high Shc ratios, experiencing an 8-year
      cumulative 2.9% and 55% relapse hazard, respectively, compared with a 22% relapse
      hazard in the total cohort. The Shc ratio had similar prognostic value for
      disease-specific survival. In multivariate models, the Shc ratio, both as a
      continuous variable and as a cut point-categorized variable, was independent of
      all measured covariates (including nodal status, tumor stage, disease stage,
      grade, estrogen receptor status, and adjuvant therapy) and was a stronger
      prognostic marker than all but nodal status. All relapsed node-positive patients
      had very high Shc ratios (>0.80; P = 0.006) in their primary tumors. Furthermore,
      the Shc ratio was a strong, independent prognostic indicator in node-negative
      patients (79 patients, 10 recurrences), with a HR of 0.086 (P = 0.02) that was
      independent of clinical markers and adjuvant therapy. Patients with low and high
      Shc ratios experienced a 3.6% and 64% relapse hazard, respectively, compared with
      20% in the total node-negative cohort.

PMID- 14583474
TI  - Thyroid cancer resistance to chemotherapeutic drugs via autocrine production of
      interleukin-4 and interleukin-10.
AB  - We investigated the mechanisms responsible for the widespread refractoriness to
      chemotherapeutic drugs observed in thyroid cancers. We show that malignant
      epithelial cells from papillary, follicular, and anaplastic thyroid carcinomas
      express high levels of Bcl-2 and Bcl-xL. Exogenous expression of either Bcl-2 or
      Bcl-xL in normal thyrocytes was sufficient to prevent chemotherapeutic drug
      induced cytotoxicity. All of the histological thyroid cancer variants examined
      produced interleukin-4 (IL-4) and interleukin-10 (IL-10), which increased Bcl-2
      and Bcl-xL levels and protected thyroid cells from chemotherapeutic agents.
      Exposure to neutralizing antibodies against IL-4 and IL-10 resulted in down
      modulation of Bcl-2 and Bcl-xL, death of a considerable percentage of thyroid
      cancer cells, and sensitization of the residual tumor population to cytotoxic
      drug-induced apoptosis. In conclusion, autocrine production of IL-4 and IL-10
      promotes thyroid tumor cell progression and resistance to chemotherapy through
      the up-regulation of antiapoptotic proteins. Thus, IL-4 and IL-10 may represent
      new therapeutic targets for the treatment of thyroid cancer.

PMID- 14583475
TI  - Glomeruloid microvascular proliferation is superior to intratumoral microvessel
      density as a prognostic marker in non-small cell lung cancer.
AB  - Glomeruloid microvascular proliferation (GMP) is a focal proliferative budding of
      endothelial cells (ECs) resembling a renal glomerulus. Whereas some experimental
      and clinical studies have suggested recently that GMPs indicate an aggressive
      angiogenic phenotype, the incidence and clinical significance of GMPs remains
      unclear. Thus, we conducted a retrospective study on GMPs in a total of 236
      patients with completely resected pathological (p-) stage I-IIIA NSCLC. ECs were
      highlighted with immunohistochemical staining using an anti-CD34 antibody, and
      GMPs were defined as focal glomerulus-like aggregates of closely associated and
      multilayer CD34-positive ECs. Expression of vascular endothelial growth factor,
      angiopoietin (Ang)-1, and Ang-2 was also examined immunohistochemically. GMPs
      were positive in 60 (25.4%) patients, and the incidence was not correlated with
      age, gender, histological type, or p-stage. The mean intratumoral microvessel
      densities for GMP-negative tumor and GMP-positive tumor were 178.2 and 184.1,
      respectively, showing that the incidence of GMPs was not correlated with
      intratumoral microvessel density (P = 0.676). There was no correlation between
      vascular endothelial growth factor expression and the incidence of GMPs, but GMPs
      were more frequently seen in Ang-1-positive tumor than in Ang-1-negative tumor.
      The 5-year survival rate of GMP-positive patients was 54.2%, which was
      significantly lower than that of GMP-negative patients (72.3%; P = 0.016). The 5
      year survival rate of higher-MVD patients (71.5%) seemed to be lower than that of
      the lower-MVD patients (63.7%), but the difference did not reach a statistical
      significance (P = 0.137). A multivariate analysis confirmed that the presence of
      GMPs was a significant prognostic factor (P = 0.003), whereas MVD was not. In
      conclusion, GMPs indicate an aggressive angiogenic phenotype associated with a
      poor prognosis in NSCLC.

PMID- 14583476
TI  - Effects of RNase L mutations associated with prostate cancer on apoptosis induced
      by 2',5'-oligoadenylates.
AB  - The RNASEL gene, a strong candidate for the hereditary prostate cancer 1 allele
      (HPC1), encodes a single-stranded specific endoribonuclease involved in the
      antiviral actions of IFNs. RNase L is activated enzymatically after binding to
      unusual 5'-phosphorylated, 2',5'-linked oligoadenylates (2-5A). Biostable
      phosphorothioate analogues of 2-5A were synthesized chemically and used to study
      the effects of naturally occurring mutations and polymorphisms in RNASEL. The 2
      5A analogues induced RNase L activity and caused apoptosis in cultures of late
      stage, metastatic human prostate cancer cell lines DU145, PC3, and LNCaP.
      However, DU145 and PC3 cells were more sensitive to 2-5A than LNCaP cells, which
      are heterozygous for an inactivating deletion mutation in RNase L. The RNase
      activities of missense variants of human RNase L were compared after expression
      in a mouse RNase L(-/-) cell line. Several variants (G59S, I97L, I220V, G296V,
      S322F, Y529C, and D541E) produced similar levels of RNase L activity as wild-type
      enzyme. In contrast, the R462Q variant, previously implicated in up to 13% of
      unselected prostate cancer cases, bound 2-5A at wild-type levels but had a 3-fold
      decrease in RNase activity. The deficiency in RNase L(R462Q) activity was
      correlated with a reduction in its ability to dimerize into a catalytically
      active form. Furthermore, RNase L(R462Q) was deficient in causing apoptosis in
      response to 2-5A consistent with its possible role in prostate cancer
      development. Our findings support the notion that RNASEL mutations and some
      variants allow tumor cells to escape a potent apoptotic pathway.

PMID- 14583477
TI  - AND-34/BCAR3, a GDP exchange factor whose overexpression confers antiestrogen
      resistance, activates Rac, PAK1, and the cyclin D1 promoter.
AB  - AND-34 is a murine protein that binds by a cdc25-like GDP exchange factor domain
      to the focal adhesion docking protein p130Cas. Overexpression of either of the
      human homologues of AND-34 and p130Cas, BCAR3 and BCAR1, respectively, has been
      reported to induce resistance to antiestrogens in breast cancer cell lines. Here
      we show that overexpression of AND-34 leads to activation of the Rho family
      GTPases Cdc42 and Rac. Consistent with these findings, BCAR3 overexpression
      induced alterations in F-actin distribution and augmented both
      autophosphorylation and kinase activity of the Cdc42/Rac-responsive
      serine/threonine kinase PAK1. p130Cas-associated BCAR3 protein was detected in
      the estrogen-independent breast cancer cell line 578-T, but not in estrogen
      dependent MCF7 or ZR-75-1 cells. Stable ZR-75-1 transfectants overexpressing
      BCAR3, but not vector-only transfectants, grew in the presence of the pure
      antiestrogen ICI 182,780. Stable transfection with RacV12, a constitutively
      active form of Rac1, also induced antiestrogen resistance in ZR-75-1 cells.
      Transient transfection of BCAR3 in estrogen-dependent MCF7 cells induced
      activation of luciferase constructs containing the proximal 1745 or 163 bp but
      not 66 bp of the cyclin D1 promoter. Such cyclin D1 promoter activation was
      inhibited by dominant negative forms of Rac1 and PAK1. Overexpression of the PAK1
      autoinhibitory domain (residues 83-149) but not an inactive PAK1 autoinhibitory
      domain point mutant (L107F) also blocked BCAR3-mediated cyclin D1 activation.
      These studies suggest that AND-34/BCAR3 induces antiestrogen resistance in breast
      cancer cell lines by a Rac1- and PAK1-dependent pathway.

PMID- 14583478
TI  - Maxizymes and small hairpin-type RNAs that are driven by a tRNA promoter
      specifically cleave a chimeric gene associated with leukemia in vitro and in
      vivo.
AB  - Many leukemias result from chromosomal translocations that lead to the generation
      of chimeric oncoproteins. Chimeric gene for the promyelocytic leukemia-retinoic
      acid receptor alpha (PML-RAR alpha) is the hallmark of acute promyelocytic
      leukemia. Specific gene silencing of an oncogene is desirable for the treatment
      of these diseases. We have previously constructed an allosterically controllable
      ribozyme (designated maxizyme) targeted for bcr-abl chimeric mRNA, whose cleavage
      activity is induced only in the presence of a specific RNA sequence of interest.
      It has been demonstrated recently that RNA interference induced by short hairpin
      type RNAs provides a powerful method for sequence-specific gene silencing. Here
      we report that DNA vector-based maxizymes and short hairpin-type RNAs driven by
      the promoter of a human gene for tRNA(Val) specifically inhibit the expression of
      the chimeric gene for PML-RAR alpha both in vitro and in vivo. Our findings
      confirm the potential utility of maxizymes and shRNAs as therapeutic agents.

PMID- 14583479
TI  - Coexistence of high levels of apoptotic signaling and inhibitor of apoptosis
      proteins in human tumor cells: implication for cancer specific therapy.
AB  - It is well known that dysfunction of the apoptotic pathway confers apoptosis
      resistance and results in a low sensitivity of human cancer cells to therapeutic
      agents. A novel strategy to overcome the resistance is to target the apoptotic
      pathway directly. To identify molecular targets in the apoptotic pathway that are
      differentially regulated in cancer and normal cells, we have examined the levels
      of apoptotic effectors and inhibitors in human tumor and normal cell lines as
      well as in cancer and normal tissues. These include three pancreatic cancer lines
      (BXPC-3, MIA PaCa-2, and Panc-1), four breast cancer cell lines (MDA-MB-231, MDA
      MB-435, MDA-MB-361, and MCF-7), and colon carcinoma line (SW620). Additionally,
      breast carcinoma tissue specimens were examined. Compared with normal human
      fibroblast and mammary epithelial cell lines, we detected high basal levels of
      caspase-3 and caspase-8 activities and active caspase-3 fragments in the tumor
      cell lines and cancer tissues in the absence of apoptotic stimuli. Furthermore,
      the tumor cells expressed high levels of survivin and XIAP, two members of the
      inhibitor of apoptosis (IAP) protein family. When the activity of these IAPs was
      blocked by expression of dominant-negative mutant survivin (survivinT34A) and
      XIAP-associated factor 1, respectively, apoptosis was induced in tumor but not
      normal cell lines. Moreover, down-regulation of both survivin and XIAP
      significantly enhanced tumor-cell apoptosis as compared with inhibition of either
      survivin or XIAP alone. These results suggest that up-regulated IAP expression
      counteracts the high basal caspase-3 activity observed in these tumor cells and
      that apoptosis in tumor cells but not normal cells can be induced by blocking IAP
      activity. Therefore, IAPs are important molecular targets for the development of
      cancer-specific therapeutic approaches.

PMID- 14583480
TI  - Induction of apoptosis by the garlic-derived compound S-allylmercaptocysteine
      (SAMC) is associated with microtubule depolymerization and c-Jun NH(2)-terminal
      kinase 1 activation.
AB  - Epidemiological and experimental carcinogenesis studies provide evidence that
      components of garlic (Allium sativum) have anticancer activity. We recently
      reported that the garlic derivative S-allylmercaptocysteine (SAMC) inhibits
      growth, arrests cells in G(2)-M, and induces apoptosis in human colon cancer
      cells (Shirin et al., Cancer Res., 61: 725-731, 2001). Because a fraction of the
      SAMC-treated cells are specifically arrested in mitosis, we examined the
      mechanism of this effect in the present study. Immunofluorescent microscopy
      revealed that the treatment of SW480 cells or NIH3T3 fibroblasts with 150 micro M
      SAMC (the IC(50) concentration) caused rapid microtubule (MT) depolymerization,
      MT cytoskeleton disruption, centrosome fragmentation and Golgi dispersion in
      interphase cells. It also induced the formation of monopolar and multipolar
      spindles in mitotic cells. In vitro turbidity assays indicated that SAMC acted
      directly on tubulin to cause MT depolymerization, apparently because it interacts
      with -SH groups on tubulin. To investigate the signaling pathways involved in
      SAMC-induced apoptosis, we assayed c-Jun NH(2)-terminal kinase (JNK) activity and
      found that treatment with SAMC caused a rapid and sustained induction of JNK
      activity. The selective JNK inhibitor SP600125 inhibited the early phase (24 h)
      but not the late phase (48 h and later) of apoptosis induced by SAMC. Expression
      of a dominant-negative mutant of JNK1 in SW480 cells inhibited apoptosis induced
      by SAMC at 24 h but had no protective effect at 48 h. JNK1(-/-) mouse embryonic
      fibroblasts were resistant to SAMC-induced apoptosis at 24 h but not at 48 h. On
      the other hand, the inhibition or abrogation of JNK1 activity did not inhibit the
      G(2)-M arrest induced by SAMC. SAMC also activated caspase-3. The general caspase
      inhibitor z-VAD-fmk inhibited both early and late phases of apoptosis induced by
      SAMC. We conclude that the garlic-derived compound SAMC exerts antiproliferative
      effects by binding directly to tubulin and disrupting the MT assembly, thus
      arresting cells in mitosis and triggering JNK1 and caspase-3 signaling pathways
      that lead to apoptosis.

PMID- 14583481
TI  - In vivo high resolution three-dimensional imaging of antigen-specific cytotoxic T
      lymphocyte trafficking to tumors.
AB  - Magnetic resonance imaging (MRI) allows noninvasive and three-dimensional
      visualization of whole organisms over time, and, therefore, would be ideally
      suited to monitor cell trafficking in vivo. Until now, systemically injected
      cells had been difficult to visualize by MRI because of relatively inefficient
      labeling methods. We developed a novel, biocompatible, and physiologically inert
      nanoparticle (highly derivatized cross-linked iron oxide nanoparticle; CLIO-HD)
      for highly efficient intracellular labeling of a variety of cell types that now
      allows in vivo MRI tracking of systemically injected cells at near single-cell
      resolution. CD8+ cytotoxic T lymphocytes labeled with CLIO-HD were detectable via
      MRI with a detection threshold of 2 cells/voxel in vitro and approximately 3
      cells/voxel in vivo in live mice. Using B16-OVA melanoma and CLIO-HD-labeled OVA
      specific CD8+ T cells, we have demonstrated for the first time high resolution
      imaging of T-cell recruitment to intact tumors in vivo. We have revealed the
      extensive three-dimensional spatial heterogeneity of T-cell recruitment to target
      tumors and demonstrated a temporal regulation of T-cell recruitment within the
      tumor. Significantly, our data indicate that serial administrations of CD8+ T
      cells appear to home to different intratumoral locations, and may, therefore,
      provide a more effective treatment regimen than a single bolus administration.
      Together, these results demonstrate that CLIO-HD is uniquely suited for
      quantitative repetitive MRI of adoptively transferred cells and that this
      approach may be particularly useful for evaluating novel cell-based therapies in
      vivo.

PMID- 14583482
TI  - Direct and bystander killing of sarcomas by novel cytosine deaminase fusion gene.
AB  - Soft tissue and bone sarcomas of the extremities can be difficult to eradicate,
      and standard treatment may require limb amputation. New therapies to decrease
      tumor size could improve the effectiveness of treatment and decrease the
      frequency of limb amputation. Cytosine deaminase (CD)-based gene therapy has been
      shown to be effective in decreasing growth of solid tumors when animals with CD
      expressing tumor cells are treated with 5 fluorocytosine (5FC), an inert prodrug
      that is converted to 5-fluorouracil (5FU) by CD. In this investigation, we used a
      novel CD-containing fusion gene to determine whether CD-based gene therapy
      affected soft tissue or bone sarcomas. The novel fusion gene (NGFR-CD) encodes
      for a protein with extracellular and transmembrane domains of human nerve growth
      factor receptor (NGFR) and cytoplasmic CD. Murine 2472 (2) sarcoma cells were
      transduced with fusion genes containing either the bacterial (NGFR-(b)CD) or
      yeast (NGFR-(y)CD) CD gene. 5FC treatment killed NGFR-(b)CD- and NGFR-(y)CD
      transduced sarcoma cells in vitro through direct and bystander effects (P <
      0.01). In contrast, 5FC treatment of mice with s.c. 2NGFR-(b)CD or 2NGFR-(y)CD
      tumors affected only 2NGFR-(y)CD tumors. 5FC had no effect on growth of NGFR
      (b)CD tumors but caused significant decrease in the size of 2NGFR-(y)CD tumors
      (51 +/- 60 versus 938 +/- 767 mm(3), treated versus control, P < 0.01).
      Evaluation of bystander killing in vivo revealed significant tumor killing, with
      a 5-fold reduction in s.c. tumor volume evident in saline versus 5FC-treated mice
      when tumors were comprised of 90% 2472 cells and 10% 2NGFR-(y)CD selected for
      fluorescence-activated cell sorting (P < 0.01). Bone sarcomas were eliminated in
      9 of 10 5FC-treated mice, compared with 11.8 +/- 6.0 mm(2) in saline-treated mice
      (P < 0.002). In addition, 5FC treatment of bone sarcomas caused a significant
      reduction in cancer-induced bone destruction (P < 0.002) and resulted in a
      reduction in the number of osteoclasts. Finally, 5FC treatment had no effect on
      animal weight or survival, whereas doses of 5FU providing equivalent tumor
      reduction as 5FC resulted in treatment-associated deaths and significant weight
      loss (P < 0.001).

PMID- 14583483
TI  - Molecular pharmacology of cancer therapy in human colorectal cancer by gene
      expression profiling.
AB  - Global gene expression profiling has potential for elucidating the complex
      cellular effects and mechanisms of action of novel targeted anticancer agents or
      existing chemotherapeutics for which the precise molecular mechanism of action
      may be unclear. In this study, decreased expression of genes required for RNA and
      protein synthesis, and for metabolism were detected in rectal cancer biopsies
      taken from patients during a 5-fluorouracil infusion. Our observations
      demonstrate that this approach is feasible and can detect responses that may have
      otherwise been missed by conventional methods. The results suggested new
      mechanism-based combination treatments for colorectal cancer and demonstrated
      that expression profiling could provide valuable information on the molecular
      pharmacology of established and novel drugs.

PMID- 14583484
TI  - Subcellular localization of radiolabeled somatostatin analogues: implications for
      targeted radiotherapy of cancer.
AB  - Copper-64 (T(1/2) = 12.7 h; beta(+), 17.4%; beta(-), 39%) has been used both in
      positron emission tomography imaging and in radiotherapy. Copper-64
      radiopharmaceuticals have shown tumor growth inhibition with a relatively low
      radiation dose in animal models; however, the mechanism of cytotoxicity has not
      been fully elucidated. These studies incorporate the use of somatostatin receptor
      positive AR42J rat pancreatic tumor cells in vitro to understand the cell killing
      mechanism of (64)Cu by focusing on subcellular distribution of the somatostatin
      analogues (64)Cu-labeled 1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic
      acid-octreotide ((64)Cu-TETA-OC) and (111)In-labeled
      diethylenetriaminepentaacetic acid-octreotide ((111)In-DTPA-OC). Cell uptake and
      organelle isolation studies were conducted on (64)Cu-TETA-OC and (111)In-DTPA-OC.
      Nuclear localization of (64)Cu and (111)In from (64)Cu-TETA-OC and (111)In-DTPA
      OC, respectively, increased over time, with 19.5 +/- 1.4% and 6.0 +/- 1.0% in the
      cell nucleus at 24 h, respectively. In pulse-chase experiments, in which (64)Cu
      TETA-OC was incubated with AR42J cells for 4 h, it was found that the nuclear
      localization of (64)Cu increased significantly over the next 20 h (from 9.8 +/-
      1.0% to 26.3 +/- 5.4%). In a control pulse-chase experiment, levels of (64)Cu
      from [(64)Cu]cupric acetate decreased from 4 to 24 h postadministration (20.6 +/-
      8.7 to 5.4 +/- 1.9), suggesting that the redistribution mechanism, or the
      kinetics of (64)Cu from (64)Cu-TETA-OC is different from that for (64)Cu from
      [(64)Cu]cupric acetate. The amount of (64)Cu from (64)Cu-TETA-OC also increased
      in the mitochondria over time, with 21.1 +/- 3.6% in the mitochondria at 24 h
      postadministration. These results suggest that localization of substantial
      quantities of (64)Cu to the cell nucleus and mitochondria may contribute to cell
      killing with (64)Cu radiopharmaceuticals.

PMID- 14583485
TI  - The proapoptotic benzodiazepine Bz-423 affects the growth and survival of
      malignant B cells.
AB  - Bz-423 is a novel proapoptotic 1,4-benzodiazepine that induces cell death via a
      superoxide signal. Previous work has shown that Bz-423 ameliorates disease in
      animal models of systemic lupus erythematosus that also have features of
      lymphoproliferative disease. Here we describe the effects of Bz-423 against a
      group of malignant B-cell lines derived from Burkitt's lymphoma. These
      experiments demonstrate that Bz-423 has cytotoxic activity against all B-cell
      lines tested, regardless of EBV status or Bcl-2 and Bcl-x(L) expression levels.
      In addition to its cytotoxic properties, we found that Bz-423 is also a potent
      antiproliferative agent that induces a G(1)-phase arrest independent of p53.
      Mechanistically, both the cytotoxicity and growth arrest are mediated by
      increased reactive oxygen species levels and appear independent of binding to the
      peripheral benzodiazepine receptor. This work further defines the biological
      activities of Bz-423 that are consistent with those of other compounds in
      clinical development for antineoplastic therapies.

PMID- 14583486
TI  - Specific oncolytic effect of a new hypoxia-inducible factor-dependent replicative
      adenovirus on von Hippel-Lindau-defective renal cell carcinomas.
AB  - Mutations in the von Hippel-Lindau (VHL) tumor suppressor gene are responsible
      for a hereditary cancer syndrome characterized by high susceptibility to
      hemangioblastomas of the retina and central nervous system, pheochromocytomas,
      and renal cell carcinomas. In agreement with its role as a tumor suppressor, the
      vast majority of spontaneous clear cell carcinomas of the kidney present loss of
      heterozygosity at the VHL locus. Recently, it has been shown that VHL works as
      the substrate recognition component of an E3 ubiquitination complex that targets
      the hypoxia-inducible factor (HIF) for proteosomal degradation. Under normal
      oxygen tension, the half-life of HIF transcription factors is extremely short
      because of its high degradation rate by the proteasome, resulting in undetectable
      HIF activity in normal cells. However, in VHL-deficient tumor cells, the HIF
      transcriptional pathway is constitutively activated because of impaired
      ubiquitination of this transcription factor. To target VHL-deficient tumors, we
      have exploited this feature to develop a conditionally replicative adenovirus
      (Ad9xHRE1A), the replication of which is HIF dependent. In this new oncolytic
      adenovirus, the expression of the E1A gene is controlled by an optimized minimal
      promoter containing HIF recognition elements. Here, we show that the induction of
      the E1A gene, as well as the viral replication and cytolytic effect of Ad9xHRE1A,
      are dependent on HIF activity. As a consequence, this virus efficiently kills VHL
      deficient cells both in vitro and in vivo, as well as cells growing under hypoxic
      conditions. These data suggest that Ad9xHRE1A could be used as a highly specific
      therapy for VHL-deficient cancers and probably many other tumors that show
      extensive hypoxic areas or increased HIF activity by genetic alterations other
      than VHL loss.

PMID- 14583487
TI  - Protective role of alpha-phenyl-N-t-butylnitrone against ionizing radiation in
      U937 cells and mice.
AB  - Ionizing radiation (IR) induces the production of reactive oxygen species (ROS),
      which play an important causative role in radiation damage. alpha-Phenyl-N-t
      butylnitrone (PBN) is one of the most widely used spin-trapping compounds for
      investigating the existence of free radicals in biological systems. We
      investigated the protective role of PBN against IR in U937 cells and mice. On
      exposure to IR, there was a distinct difference between the control cells and the
      cells pretreated with PBN in regard to viability, cellular redox status, and
      oxidative damage to cells. Lipid peroxidation, oxidative DNA damage, and protein
      oxidation were significantly lower in the cells treated with PBN when the cells
      were exposed to IR. Although the activities of antioxidant enzymes were
      comparable in PBN-treated and control cells, the [GSSG]:[GSH + GSSG] ratio and
      the generation of intracellular ROS were higher and the [NADPH]:[NADP(+) + NADPH]
      ratio was lower in control cells compared with PBN-treated cells. The IR-induced
      mitochondrial damage reflected by the altered mitochondrial permeability
      transition, the increase in the accumulation of ROS, the reduction of ATP
      production, and the morphological change were significantly higher in control
      cells compared with PBN-treated cells. PBN administration for 14 days with a
      daily dosage of 30 mg/kg provided substantial protection against killing and
      oxidative damage to mice exposed to whole body irradiation. These data indicate
      that PBN may have great application potential as a new class of in vivo,
      nonsulfur-containing radiation protector.

PMID- 14583488
TI  - Identification and characterization of an inhibitor of eukaryotic elongation
      factor 2 kinase against human cancer cell lines.
AB  - Recent evidence suggests that the machinery of protein synthesis may provide
      novel targets for anticancer drugs. For example, aberrations in protein synthesis
      are commonly encountered in established cancers, and disruption by mutation or
      overexpression of translation factors can cause cellular transformation. We
      previously demonstrated that the activity of eukaryotic elongation factor 2 (eEF
      2) kinase was markedly increased in several forms of malignancy and that
      nonspecific inhibitors of this enzyme promoted cell death. On the basis of the
      predicted amino acid sequence of eEF-2 kinase deduced from the cloned cDNA, we
      hypothesized that inhibitors of prokaryotic histidine kinases might also inhibit
      the activity of eEF-2 kinase. We describe herein the screening of a series of
      imidazolium histidine kinase inhibitors and the identification of an active lead
      compound, NH125. NH125 inhibited eEF-2 kinase activity (IC(50) = 60 nM) in vitro,
      blocked the phosphorylation of eEF-2 in intact cells, and showed relative
      selectivity over other protein kinases: protein kinase C (IC(50) = 7.5 microM),
      protein kinase A (IC(50) = 80 microM), and calmodulin-dependent kinase II (IC(50)
      > 100 microM). NH125 decreased the viability of 10 cancer cell lines with IC(50)s
      ranging from 0.7 to 4.7 microM. Forced overexpression of eEF-2 kinase in a glioma
      cell line produced 10-fold resistance to NH125. In conclusion, these results
      suggest that identification of potent inhibitors of eEF-2 kinase may lead to the
      development of new types of anticancer drugs.

PMID- 14583489
TI  - A prodrug strategy using ONYX-015-based replicating adenoviruses to deliver
      rabbit carboxylesterase to tumor cells for conversion of CPT-11 to SN-38.
AB  - ONYX-015 has been used successfully in the clinic as a cancer therapeutic in
      combination with chemotherapy. The combination of ONYX-015 and chemotherapy
      appears to be more efficacious than either regimen alone. In this study, we try
      to enhance this combination by "arming" ONYX-015 with a therapeutic transgene, an
      approach more commonly used with nonreplicating viruses in the context of gene
      therapy. We chose the prodrug converting enzyme carboxylesterase (CE), which
      converts the camptothecin derivative CPT-11 (irinotecan) to the much more potent
      chemotherapeutic SN-38. The transgene was introduced into three distinct
      positions in the E3 region of the adenovirus genome to allow either early or late
      expression during the virus life cycle. We demonstrate that each of these ONYX
      015-based adenoviruses expresses an active CE enzyme that can efficiently convert
      CPT-11 to SN-38. Furthermore, the cytotoxicity of CE-expressing viruses, but not
      control viruses, is enhanced significantly in the presence of the prodrug.
      Finally, we demonstrate that we can achieve transgene expression and activity in
      vivo in a human tumor xenograft model, and that treatment with a CE-expressing
      virus in combination with CPT-11 enhances survival of tumor-bearing mice. These
      results indicate that the addition of a prodrug converting enzyme may be a
      feasible approach to additionally enhance the efficacy of replicating
      adenoviruses as cancer therapeutics.

PMID- 14583491
TI  - Human NADPH-cytochrome p450 reductase overexpression does not enhance the aerobic
      cytotoxicity of doxorubicin in human breast cancer cell lines.
AB  - Doxorubicin is a useful antineoplastic drug with multiple mechanisms of
      cytotoxicity. One such mechanism involves the reductive bioactivation of the
      quinone ring to a semiquinone radical, which can exert direct toxic effects
      and/or undergo redox cycling. We hypothesized that human NADPH-cytochrome p450
      reductase (CYPRED) catalyzes doxorubicin reduction and that overexpression of
      this enzyme sensitizes human breast cancer cell lines to the aerobic cytotoxicity
      of doxorubicin. cDNA-expressed human CYPRED catalyzed doxorubicin reduction,
      measured as the rate of doxorubicin-stimulated NADPH consumption. Using a bank of
      17 human liver microsomal samples, the rate of doxorubicin reduction correlated
      with CYPRED catalytic activity and CYPRED protein immunoreactivity.
      Diphenyliodonium chloride, a mechanism-based inactivator of CYPRED, inhibited
      CYPRED activity and doxorubicin reduction in human liver microsomes with similar
      concentration dependence. Stably transfected clones of MDA231 human breast cancer
      cells overexpressing human CYPRED immunoreactive protein and catalytic activity
      showed enhanced sensitivity to the aerobic cytotoxicity of tirapazamine, a
      bioreductive drug known to be activated by CYPRED; however, no sensitization to
      the cytotoxic effects of doxorubicin was observed. Although human CYPRED is an
      important catalyst of doxorubicin reduction, overexpression of this enzyme does
      not confer enhanced sensitivity of human breast cancer cells to the aerobic
      cytotoxicity of doxorubicin.

PMID- 14583490
TI  - Lipid-mediated protein delivery of suicide nucleoside kinases.
AB  - Nucleoside kinases from several species are investigated as suicide genes for
      treatment of malignant tumors by combined gene/chemotherapy. In the present
      study, we have investigated a novel strategy where nucleoside kinase proteins are
      directly delivered to cells without delivery of genetic material. We used a mix
      of a trifluoroacetylated lipopolyamine and dioleoyl phosphatidylethanolamine
      (BioPorter) to form protein-lipid complexes containing either recombinant herpes
      simplex virus type-1 thymidine kinase or Drosophila melanogaster multisubstrate
      deoxyribonucleoside kinase. We showed that the nucleoside kinase containing
      protein-lipid complexes was imported into human osteosarcoma and Chinese hamster
      ovary cell lines by endocytosis and that the enzymes were delivered to the
      cytosol and nucleus. The nucleoside kinases imported into the cell lines retained
      enzymatic activity, and the cells treated with the enzyme-lipid complexes showed
      increased sensitivity to nucleoside analogues, such as ganciclovir, (E)-5-(2
      bromovinyl)-2'-deoxyuridine, and 1-beta-D-arabinofuranosylthymine. Our results
      show that direct delivery of suicide gene proteins to cells may be an alternative
      approach to conventional suicide gene therapy strategies.

PMID- 14583492
TI  - The antiangiogenic agent SU5416 down-regulates phorbol ester-mediated induction
      of cyclooxygenase 2 expression by inhibiting nicotinamide adenine dinucleotide
      phosphate oxidase activity.
AB  - Increased expression of cyclooxygenase (COX) 2 and the production of PGs appear
      to provide a survival advantage to transformed cells through the inhibition of
      apoptosis, increased attachment to extracellular matrix, increased invasiveness
      and the stimulation of angiogenesis. The purpose of this study was to determine
      whether an angiogenic antagonist, SU5416, could inhibit endogenous and phorbol 12
      myristate 13-acetate (PMA)-mediated induction of COX-2 expression. SU5416 (5
      micro M) inhibited endogenous as well as PMA-mediated induction of COX-2
      expression when analyzed by immunoblot and Northern blot analysis. However, COX-1
      expression remained unchanged under similar conditions. PMA is a potent inducer
      of reactive oxygen species that can play an important role during the induction
      of COX-2 expression. Our results demonstrated that PMA-mediated induction of COX
      2 expression was found to be dependent on NADPH oxidase activity. An inhibitor of
      NADPH oxidase (diphenyleneiodonium chloride) blocked the PMA-mediated induction
      of COX-2 expression. The oxidase complex exhibited a temporal pattern of
      activation after exposure to PMA in which maximum activation was observed at 30
      min after the addition of PMA. Activation of NADPH oxidase was also inhibited by
      SU5416, whereas an inhibitor of epidermal growth factor receptor signaling was
      unable to prevent the PMA-mediated induction of NADPH oxidase activity. When we
      blocked the PMA-mediated production of reactive oxygen species by blocking NADPH
      oxidase with SU5416, COX-2 expression and PGE(2) synthesis were also inhibited.
      Our results suggest that inhibition of NADPH oxidase activity, blocking of COX-2
      expression, and PGE(2) synthesis may represent novel targets for SU5416.

PMID- 14583493
TI  - Proteomic profiling drug-induced apoptosis in non-small cell lung carcinoma:
      identification of RS/DJ-1 and RhoGDIalpha.
AB  - The growing knowledge of the tight connection between apoptosis and cancer has
      lead to an explosion of research revolving around apoptotic induction with
      chemotherapeutic agents and small molecule inhibitors. The chemotherapeutic agent
      paclitaxel (Taxol) activates mitogen-activated protein kinase kinase
      (MEK)/extracellular signal-regulated kinase and, combined with MEK inhibition,
      synergistically enhances apoptosis. Here we implement a proteomic approach using
      two-dimensional gels coupled with mass spectrometry to identify proteins altered
      with this coordinated combination treatment. We found that the combined treatment
      of paclitaxel and MEK inhibitor uniquely altered the proteins RS/DJ-1 (RNA
      binding regulatory subunit/DJ-1 PARK7) and RhoGDIalpha (Rho GDP-dissociation
      inhibitor alpha). Functional proteomic analysis by exogenous expression or short
      interfering RNA targeting confirmed a role in survival and apoptosis for these
      proteins. Analysis of primary lung tumors with matched adjacent normal tissue
      confirmed RS/DJ-1 overexpression in non-small cell lung carcinoma. This study
      shows the power of proteomic profiling coupled with functional analysis for the
      discovery of novel molecular targets and potential cancer cell-specific
      biomarkers.

PMID- 14583494
TI  - Enhanced radiosensitization with gemcitabine in mismatch repair-deficient HCT116
      cells.
AB  - Gemcitabine [2',2'-difluoro-2'-deoxycytidine (dFdCyd)] is a potent ionizing
      radiation sensitizer in solid tumor cells in vitro and in vivo. Previously, we
      have demonstrated (Shewach et al., Cancer Res., 54: 3218-3223, 1994) a strong
      correlation between depletion of dATP (caused by dFdCyd diphosphate-mediated
      inhibition of ribonucleotide reductase) and radiosensitization. In addition, we
      and others (Latz et al., Int. J. Radiat. Oncol. Biol. Phys., 41: 875-882, 1998;
      Ostruszka and Shewach, Cancer Res., 60: 6080-6088, 2000) have shown that the
      accumulation of cells in S phase prior to irradiation is also important for
      radiosensitization with dFdCyd. This led us to hypothesize that the incorporation
      of incorrect nucleotides because of the dATP pool imbalance was important for
      radiosensitization with dFdCyd, and, therefore, cells deficient in mismatch
      repair (MMR) would exhibit greater radiosensitization. We tested this hypothesis
      by evaluating the ability of HCT116 colon carcinoma cell lines, which differ in
      MMR proficiency, to be radiosensitized by dFdCyd. The MMR-proficient cell line
      (HCT116 + ch3) was more sensitive to dFdCyd alone than were the MMR-deficient
      cell lines (HCT116, HCT116 + ch2, and HCT116 p53(-/-)). Interestingly, the MMR
      proficient cells could not be radiosensitized at concentrations of dFdCyd
      <or=IC(90), although extremely high concentrations of dFdCyd (>IC(96)) enhanced
      cell killing with radiation. In contrast, the MMR-deficient cells were
      radiosensitized at concentrations of dFdCyd <or=IC(50), with radiation
      enhancement ratios of approximately 1.5. Cell cycle analysis, using dual
      parameter flow cytometry, demonstrated that all of the cell lines accumulated in
      S phase after dFdCyd treatment, and, shortly after irradiation, a prominent but
      transient G(2)-M block was observed. In the MMR-deficient cells, the IC(50) for
      dFdCyd produced a >or=80% decrease in dATP within 4 h after drug addition, and
      this low dATP level was maintained for another 12-20 h. Although the IC(50) of
      dFdCyd was unable to sustain a >80% decrease in the dATP level in the MMR
      proficient cells, the IC(90) did achieve this level of dATP depletion; however,
      it was unable to radiosensitize the MMR-proficient cells. Similar results were
      obtained with HCT116 cells, in which the MMR deficiency was corrected by
      transfection with a vector containing the hMLH1 cDNA. In addition, the deletion
      of p53 did not increase radiation enhancement ratios. These results demonstrate
      that MMR deficiency promotes radiosensitization with dFdCyd. We suggest that dATP
      depletion produces errors of replication in MMR-deficient cells, which, if left
      unrepaired, enhances cell death by ionizing radiation.

PMID- 14583495
TI  - HMN-176, an active metabolite of the synthetic antitumor agent HMN-214, restores
      chemosensitivity to multidrug-resistant cells by targeting the transcription
      factor NF-Y.
AB  - HMN-176 ((E)-4-[[2-N-[4-methoxybenzenesulfonyl]amino]stilbazole]1-oxide) is an
      active metabolite of HMN-214 ((E)-4-[2-[2-(N-acetyl-N-[4
      methoxybenzenesulfonyl]amino)stilbazole]]1-oxide), which has a potent antitumor
      activity in mouse xenograft models. In this study, we show that HMN-176
      circumvents multidrug resistance in a K2 human ovarian cancer subline selected
      for Adriamycin resistance (K2/ARS). Upon treatment of K2/ARS cells with 3 microM
      HMN-176, the GI(50) of Adriamycin for the cells decreased by approximately 50%.
      To explore the molecular mechanism of this effect, we assessed the expression of
      the multidrug resistance gene (MDR1), which is constitutive in K2/ARS cells, at
      both the protein and the mRNA level. Western and reverse transcription-PCR
      analysis revealed that the expression of MDR1 was significantly suppressed by
      treatment with HMN-176. Furthermore, when administered p.o., HMN-214 suppressed
      the expression of MDR1 mRNA in a mouse xenograft model implanted with KB-A.1, an
      Adriamycin-resistant cell line. Luciferase reporter fusion gene analysis
      demonstrated that HMN-176 inhibited the Y-box-dependent promoter activity of the
      MDR1 gene in a dose-dependent manner. Moreover, we show by electrophoretic
      mobility shift assay that HMN-176 inhibits the binding of NF-Y, which is thought
      to be an essential factor for the basal expression of MDR1, to its target Y-box
      consensus sequence in the MDR-1 promoter. Inhibition of MDR-1 expression was
      achieved with pharmacological concentrations of HMN-176, suggesting that HMN-176
      may act by two different mechanisms-cytotoxicity and MDR1 down-regulation
      simultaneously. The data presented strongly suggest that the antitumor mechanism
      of HMN-176 (or its prodrug HMN-214 in vivo) is quite different from those of
      known antitumor agents.

PMID- 14583496
TI  - Antigen-specific immunity in neuroblastoma patients: antibody and T-cell
      recognition of NY-ESO-1 tumor antigen.
AB  - Neuroblastoma cells have been shown to express molecularly defined tumor
      associated antigens, which could represent potential targets of T and/or B cell
      mediated immunity. However, the existence of a spontaneous immune response to
      such tumor antigens in neuroblastoma patients has yet to be investigated. In the
      present work we addressed the issue of whether NY-ESO-1, a germ cell antigen
      aberrantly expressed in different tumor types, is expressed by neuroblastoma
      cells and may represent a target for humoral and/or cellular immune responses in
      neuroblastoma patients. We found that a large fraction of neuroblastoma biopsies,
      independently from the clinical stage and degree of tumor cell differentiation,
      expressed significant levels of NY-ESO-1 as assessed by reverse transcription-PCR
      and immunohistochemistry. NY-ESO-1-specific IgG antibodies were detected in the
      sera of 10% of neuroblastoma patients with stage III or IV disease, but not in
      patients in clinical remission or with earlier stages. This suggests that
      antibody production occurred as a late event in the course of disease. NY-ESO-1
      specific immune responses were observed for CD4(+) and CD8(+) T cells from
      peripheral blood lymphocytes in 4 of 8 neuroblastoma patients, as detected by IFN
      gamma enzyme-linked immunospot assay after in vitro stimulation either with the
      NY-ESO-1 recombinant protein or with the HLA-A2-restricted peptide NY-ESO-1(157
      167). NY-ESO-1-specific CD4(+) and CD8(+) T cells were also able to recognize NY
      ESO-1 expressing neuroblastoma cells. The presence of T cells specific for NY-ESO
      1 antigen was not associated with the stage of disease, or to the presence or
      absence of NY-ESO-1 specific antibodies. We conclude that NY-ESO-1 is an
      immunogenic antigen in neuroblastoma patients and represents a candidate target
      for immune-based therapy.

PMID- 14583497
TI  - Intratumoral vaccination with vaccinia-expressed tumor antigen and granulocyte
      macrophage colony-stimulating factor overcomes immunological ignorance to tumor
      antigen.
AB  - Using a murine transitional cell carcinoma tumor model, MB49, which naturally
      expresses the male antigen HY, we evaluated whether tumor ignorance as determined
      by lack of a systemic immune response could be overcome by immunization with
      vaccinia expressed tumor antigen and granulocyte macrophage colony-stimulating
      factor. Systemic tumor ignorance of MB49 was demonstrated by the lack of a
      splenic HY-specific CTL response in MB49-bearing female mice. In contrast, we
      demonstrated HY-specific CTL priming in the draining lymph nodes. MB49-bearing
      female B6 mice were immunized with VVHY+VVGMCSF intratumorally or in the
      contralateral flank. Intratumoral VVHY, VVGMCSF, and keyhole limpet hemocyanin
      (to produce CD4 help) generated splenic HY-specific CD8 CTLs, whereas
      immunization with the combination in the contralateral flank or single agents
      given intratumorally failed to yield a splenic response. Purified male T cells
      injected intratumorally, as a source of HY antigen, also generated a HY-specific
      response, whereas contralateral immunizations did not. These finding expand the
      understanding of tumor immunological ignorance and support intratumoral
      vaccination as a strategy for immunotherapy of established tumors.

PMID- 14583498
TI  - Prognostic value of epidermal growth factor receptor in patients with
      glioblastoma multiforme.
AB  - Glioblastoma multiforme (GBM) frequently involves amplification and alteration of
      the epidermal growth factor receptor (EGFR) gene, resulting in overexpression of
      varied mutations, including the most common mutation, EGFRvIII, as well as wild
      type EGFR (EGFRwt). To test the prognostic value of EGFR, we retrospectively
      analyzed the relationship between treatment outcomes and the EGFR gene in 87
      newly diagnosed adult patients with supratentorial GBM enrolled in clinical
      trials. The EGFR gene status was assessed by Southern blots and EGFR expression
      by immunohistochemistry using three monoclonal antibodies (EGFR.25 for EGFR,
      EGFR.113 for EGFRwt, and DH8.3 for EGFRvIII). EGFR amplification was detected in
      40 (46%) of the 87 GBM patients; in 39 (97.5%) of these, EGFR was overexpressed.
      On the other hand, in 46 of 47 patients without EGFR amplification (97.9%), no
      EGFR overexpression was present. There was a close correlation between EGFR
      amplification and EGFR overexpression (P < 0.0001). EGFRwt was overexpressed in
      27 of the 40 (67.5%) patients with, and in none without, EGFR amplification (P <
      0.0001). Similarly, EGFRvIII was overexpressed in 18 (45.0%) of 40 patients with
      and in 4 (8.5%) of 47 patients without EGFR amplification (P < 0.0001). The
      finding that 8 (20%) of the patients with EGFR amplification/EGFR overexpression
      manifested overexpression of neither EGFRwt nor EGFRvIII indicates that they
      overexpressed other types of EGFR. Multivariate analysis demonstrated that EGFR
      amplification was an independent, significant, unfavorable predictor for overall
      survival (OS) in all patients (P = 0.038, HR = 1.67). With respect to the
      relationship of age to EGFR prognostication, the EGFR gene status was a more
      significant prognosticator in younger patients, particularly in those <60 years
      (P = 0.0003, HR = 3.15), whereas not so in older patients. EGFRvIII
      overexpression, on the other hand, was not predictive for OS. However, in
      patients with EGFR amplification, multivariate analysis revealed that EGFRvIII
      overexpression was an independent, significant, poor prognostic factor for OS (P
      = 0.0044, HR = 2.71). This finding indicates that EGFRvIII overexpression in the
      presence of EGFR amplification is the strongest indicator of a poor survival
      prognosis. In GBM patients, EGFR is of significant prognostic value for
      predicting survival, and the overexpression of EGFRvIII with amplification plays
      an important role in enhanced tumorigenicity.

PMID- 14583499
TI  - Proteomic profiling of urinary proteins in renal cancer by surface enhanced laser
      desorption ionization and neural-network analysis: identification of key issues
      affecting potential clinical utility.
AB  - Recent advances in proteomic profiling technologies, such as surface enhanced
      laser desorption ionization mass spectrometry, have allowed preliminary profiling
      and identification of tumor markers in biological fluids in several cancer types
      and establishment of clinically useful diagnostic computational models. There are
      currently no routinely used circulating tumor markers for renal cancer, which is
      often detected incidentally and is frequently advanced at the time of
      presentation with over half of patients having local or distant tumor spread. We
      have investigated the clinical utility of surface enhanced laser desorption
      ionization profiling of urine samples in conjunction with neural-network analysis
      to either detect renal cancer or to identify proteins of potential use as
      markers, using samples from a total of 218 individuals, and examined critical
      technical factors affecting the potential utility of this approach. Samples from
      patients before undergoing nephrectomy for clear cell renal cell carcinoma (RCC;
      n = 48), normal volunteers (n = 38), and outpatients attending with benign
      diseases of the urogenital tract (n = 20) were used to successfully train neural
      network models based on either presence/absence of peaks or peak intensity
      values, resulting in sensitivity and specificity values of 98.3-100%. Using an
      initial "blind" group of samples from 12 patients with RCC, 11 healthy controls,
      and 9 patients with benign diseases to test the models, sensitivities and
      specificities of 81.8-83.3% were achieved. The robustness of the approach was
      subsequently evaluated with a group of 80 samples analyzed "blind" 10 months
      later, (36 patients with RCC, 31 healthy volunteers, and 13 patients with benign
      urological conditions). However, sensitivities and specificities declined
      markedly, ranging from 41.0% to 76.6%. Possible contributing factors including
      sample stability, changing laser performance, and chip variability were examined,
      which may be important for the long-term robustness of such approaches, and this
      study highlights the need for rigorous evaluation of such factors in future
      studies.

PMID- 14583500
TI  - Genetic variation in angiotensin I-converting enzyme (ACE) and breast cancer
      risk: the multiethnic cohort.
AB  - The A-240T and I/D polymorphisms in the angiotensin I-converting enzyme (ACE)
      gene are markers of circulating ACE levels and have been associated with numerous
      cardiovascular disease outcomes. More recently, the low-activity A and I alleles
      at these polymorphic sites have been inversely related with breast cancer risk.
      We assessed the relationship between the A-240T and I/D ACE variants and breast
      cancer risk in a case-control analysis (n = 1263 cases with invasive breast
      cancer and 2269 controls) among African-American, Japanese, Latina, and white
      women in the Multiethnic Cohort Study. Odds ratios and 95% confidence intervals
      are presented adjusted for established breast cancer risk factors. Among all
      women combined, we observed no significant association between the A-240T
      polymorphism and breast cancer risk. For the I/D polymorphism, contrary to
      expectation, women with the I/I genotype had a marginally significant increase in
      breast cancer risk (versus DD genotype: odds ratio, 1.30; 95% confidence
      interval, 1.05-1.61), although associations were not entirely consistent across
      ethnic groups. These data do not support the hypothesis that women with lower ACE
      levels, as predicted by the low-activity A and I ACE alleles, are at reduced risk
      of breast cancer. Overall, these results suggest that the A-240T and I/D ACE
      polymorphisms are not likely to be strong predictors of breast cancer risk.

PMID- 14583501
TI  - Synergy between selenium and vitamin E in apoptosis induction is associated with
      activation of distinctive initiator caspases in human prostate cancer cells.
AB  - The ongoing Selenium and Vitamin E Chemoprevention Trial is designed to evaluate
      the efficacy of these two agents, either individually or in combination, in
      reducing the incidence of prostate cancer in healthy men over 55 years of age.
      Little information, however, is available on the potential synergy between
      vitamin E and selenium in chemoprevention. The present study was aimed at
      addressing this gap of knowledge with the use of the androgen-unresponsive, p53
      null, PC-3 human prostate cancer cell line. The growth-inhibitory activity of
      vitamin E appeared to be dependent on the chemical form. In our hands, D-alpha
      tocopheryl succinate (VES) was much more potent than either DL-alpha-tocopherol
      or D-alpha-tocopheryl acetate. Combining VES with methylseleninic acid (MSA), a
      selenium metabolite, produced a synergistic effect on cell growth suppression.
      The synergy was accounted for primarily by an augmented apoptotic response.
      Poly(ADP-ribose) polymerase cleavage and activation of specific caspases were
      confirmed by Western blot analysis. The caspases that were commonly modulated by
      either VES or MSA included initiator caspases-8 and -10, as well as executioner
      caspases-3, -6, and -7. In contrast, caspase-9 was activated only by VES, whereas
      caspases-1 and -12 were activated only by MSA. Based on the above information, it
      is proposed that the mitochondrial pathway and the endoplasmic reticulum
      stress/cytokine signaling pathway might be involved in apoptosis induction by VES
      and MSA, respectively. These two pathways may act in a cooperative manner to
      switch on the full force of the apoptotic machinery when cells are treated with
      both VES and MSA.

PMID- 14583502
TI  - Expressed sequence tags: clean before using. Correspondence re: Z. Wang et al.,
      computational analysis and experimental validation of tumor-associated
      alternative RNA splicing in human cancer. Cancer Res., 63: 655-657, 2003.

PMID- 14583506
TI  - Cascading trophic impacts of reduced biomass in the Ross Sea, Antarctica: just
      the tip of the iceberg?

PMID- 14583507
TI  - Thermal tolerances of deep-sea hydrothermal vent animals from the Northeast
      Pacific.

PMID- 14583508
TI  - Light production by the arm tips of the deep-sea cephalopod Vampyroteuthis
      infernalis.
AB  - The archaic, deep-sea cephalopod Vampyroteuthis infernalis occurs in dark, oxygen
      poor waters below 600 m off Monterey Bay, California. Living specimens, collected
      gently with a remotely operated vehicle (ROV) and quickly transported to a
      laboratory ashore, have revealed two hitherto undescribed means of bioluminescent
      expression for the species. In the first, light is produced by a new type of
      organ located at the tips of all eight arms. In the second, a viscous fluid
      containing microscopic luminous particles is released from the arm tips to form a
      glowing cloud around the animal. Both modes of light production are apparently
      linked to anti-predation strategies. Use of the tip-lights is readily educed by
      contact stimuli, while fluid expulsion has a much higher triggering threshold.
      Coelenterazine and luciferase are the chemical precursors of light production.
      This paper presents observations on the structure and operation of the arm-tip
      light organs, the character of the luminous cloud, and how the light they produce
      is incorporated into behavioral patterns.

PMID- 14583509
TI  - Patterns and processes of larval emergence in an estuarine parasite system.
AB  - Trematode parasites in intertidal estuaries experience constantly varying
      conditions, with the presence or absence of water potentially limiting larval
      transport between hosts. Given the short life spans (< or =24 h) of cercariae,
      emergence timing should be optimized to enhance the probability of successful
      transmission. In the present study, field measurements and laboratory experiments
      identified processes that regulate the emergence of cercariae from their first
      intermediate snail hosts in an intertidal marsh. Larvae emerged over species
      specific temperature ranges, exclusively during daylight hours, and only when
      snails were submerged. The three factors operate over different temporal scales:
      temperature monthly, light diurnally (24-h period), and water depth tidally (12-h
      period). Each stimulus creates a necessary condition for the next, forming a
      hierarchy of environmental cues. Emergence as the tide floods would favor
      transport within the estuary, and light may trigger direct (downward or upward)
      swimming toward host habitats. Abbreviated dispersal would retain asexually
      reproduced cercariae within the marsh, and local mixing would diversify the gene
      pool of larvae encysting on subsequent hosts. In contrast to the timing of
      cercarial release, emergence duration was under endogenous control. Duration of
      emergence decreased from sunrise to sunset, perhaps in response to the
      diminishing lighted interval as the day progresses. Circadian rhythms that
      control cercarial emergence of freshwater species (including schistosomes) are
      often set by the activity patterns of subsequent hosts. In this estuary, however,
      the synchronizing agent is the tides. Together, exogenous and endogenous factors
      control emergence of trematode cercariae, mitigating the vagaries of an
      intertidal environment.

PMID- 14583510
TI  - Larval development and metamorphosis in Pleurobranchaea maculata, with a review
      of development in the notaspidea (Opisthobranchia).
AB  - Pleurobranchaea maculata is a carnivorous notaspidean that is common in New
      Zealand. This species produces small eggs (diameter 100 microm) and
      planktotrophic veligers that hatch in 8 d and are planktonic for 3 weeks before
      settling on biofilmed surfaces (14 degrees C). Larval development is known in
      detail for only two other notaspidean species, P. japonica and Berthellina
      citrina. In all three species of pleurobranchids, mantle and shell growth show
      striking differences from veligers of other opisthobranch taxa. In young veligers
      of pleurobranchids, the shell is overgrown by the mantle, new shell is added by
      cells other than those of the mantle fold, and an operculum does not form. Thus
      some "adult" traits (e.g., notum differentiation, mechanism of shell growth, lack
      of operculum) are expressed early in larval development. This suggests that
      apomorphies characteristic of adult pleurobranchids evolved through heterochrony,
      with expression in larvae of traits typical of adults of other clades. The
      protoconch is dissolved post-settlement and not cast off as occurs in other
      opisthobranch orders, indicating that shell loss is apomorphic. P. maculata
      veligers are atypical of opisthobranchs in having a field of highly folded cells
      on the lower velar surface, a mouth that is posterior to the metatroch, and a
      richly glandular, possibly chemodefensive mantle. These data indicate that
      notaspidean larvae are highly derived in terms of the novel traits and the timing
      of morphogenic events. Phylogenetic analysis must consider embryological origins
      before assuming homology, as morphological similarities (e.g., shell loss) may
      have developed through distinct mechanisms.

PMID- 14583511
TI  - Effects of allogeneic contact on life-history traits of the colonial ascidian
      Botryllus schlosseri in Monterey Bay.
AB  - The formation of chimeric colonies following allogeneic contact between benthic
      invertebrates may strongly affect colony fitness. Here we show that, in a field
      population of the colonial ascidian Botryllus schlosseri in Monterey Bay,
      California, more than 20% of all colonies occur in allogeneic contact with
      conspecifics. We experimentally assessed the effects of allogeneic contact on the
      following life-history traits under natural field conditions: growth, age and
      size at first reproduction, and egg production (fecundity). When compared with
      isolated colonies, and in some cohorts also with colonies that rejected
      allogeneic neighbors, colonies that fused with neighbors incurred reduced fitness
      in terms of most life-history traits measured. We propose that one of the
      benefits of precise allorecognition is that, in fused colonies, it limits the
      unit of selection to chimeric individuals composed of closely related kin.

PMID- 14583512
TI  - Effect of disturbance on assemblages: an example using porifera.
AB  - Extensive sponge assemblages are found in a number of habitats at Lough Hyne
      Marine Nature Reserve. These habitats are unusual in experiencing a range of
      environmental conditions, even though they are only separated by small geographic
      distances (1-500 m), reducing the possibility of confounding effects between
      study sites (e.g., silica concentrations and temperature). Sponge assemblages
      were examined on ephemeral (rocks), stable (cliffs), and artificial (slate
      panels) hard substrata from high- and low-energy environments that were used to
      represent two measures of disturbance (flow rate and habitat stability). Sponge
      assemblages varied considerably between habitat types such that only 26% (25
      species) of species reported were common to both rock and cliff habitats. Seven
      species (of a total of 96 species) were found in the least-developed assemblages
      (slate panels) and were common to all habitats. Sponge assemblages on rocks and
      panels varied little between high- and low-energy environments, whereas
      assemblages inhabiting cliffs varied considerably. Assemblage composition was
      visualized using Bray-Curtis similarity analysis and Multi-Dimensional Scaling,
      which enabled differences and similarities between sponge assemblages to be
      visualized. Cliffs from high- and low-energy sites had different assemblage
      compositions compared to large rocks, small rocks, and panels, all of which had
      similar assemblages irrespective of environmental conditions. Differences in
      assemblages were partially attributed to sponge morphology (shape), as certain
      morphologies (e.g., arborescent species) were excluded from 2-D rock habitats.
      Other mechanisms were also considered responsible for the sponge assemblages
      associated with different habitats.

PMID- 14583515
TI  - Long duration three-dimensional imaging of calcium waves in zebrafish using
      multiphoton fluorescence microscopy.

PMID- 14583513
TI  - Phenotypic plasticity of HSP70 and HSP70 gene expression in the Pacific oyster
      (Crassostrea gigas): implications for thermal limits and induction of thermal
      tolerance.
AB  - Pacific oysters, Crassostrea gigas, living at a range of tidal heights, routinely
      encounter large seasonal fluctuations in temperature. We demonstrate that the
      thermal limits of oysters are relatively plastic, and that these limits are
      correlated with changes in the expression of one family of heat-shock proteins
      (HSP70). Oysters were cultured in the intertidal zone, at two tidal heights, and
      monitored for changes in expression of cognate (HSC) and inducible (HSP) heat
      shock proteins during the progression from spring through winter. We found that
      the "control" levels (i.e., prior to laboratory heat shock) of HSC77 and HSC72
      are positively correlated with increases in ambient temperature and were
      significantly higher in August than in January. The elevated level of HSCs during
      the summer was associated with moderate, 2-3 degrees C, increases in the upper
      thermal limits for survival. We measured concomitant increases in the threshold
      temperatures (T(on)) required for induction of HSP70. Total hsp70 mRNA expression
      reflected the seasonal changes in the expression of inducible but not cognate
      members of the HSP70 family of proteins. A potential cost of increased T(on) in
      the summer is that there was no extension of the upper thermal limits for
      survival (i.e., induction of thermotolerance) after sublethal heat shock at
      temperatures that were sufficient to induce thermotolerance during the winter
      months.

PMID- 14583516
TI  - Squid sperm to clam eggs: imaging wet samples in a scanning electron microscope.

PMID- 14583517
TI  - Formation of the blastoderm and yolk syncytial layer in early squid development.

PMID- 14583518
TI  - Lithium chloride inhibits development along the animal vegetal axis and anterior
      midline of the squid embryo.

PMID- 14583519
TI  - HNK-1/N-CAM immunoreactivity correlates with ciliary patterns during development
      of the polychaete Capitella sp. I.

PMID- 14583520
TI  - Ryanodine-sensitive calcium flux regulates motility of Arbacia punctulata sperm.

PMID- 14583521
TI  - Axotomy inhibits the slow axonal transport of tubulin in the squid giant axon.

PMID- 14583522
TI  - Interactions between recombinant conventional squid kinesin and native myosin-V.

PMID- 14583523
TI  - Rab-GDI inhibits myosin V-dependent vesicle transport in squid giant axon.

PMID- 14583524
TI  - Cytoskeletal events preceding polar body formation in activated Spisula eggs.

PMID- 14583525
TI  - Three-dimensional birefringence distribution in reconstituted asters of Spisula
      oocytes revealed by scanned aperture polarized light microscopy.

PMID- 14583526
TI  - Rho-kinase is required for myosin-II-mediated vesicle transport during M-phase in
      extracts of clam oocytes.

PMID- 14583527
TI  - An experimental approach to the study of gap-junction-mediated cell death.

PMID- 14583528
TI  - Apoptosis in Microciona prolifera Allografts.

PMID- 14583529
TI  - The decorated clot: Binding of agents of the innate immune system to the fibrils
      of the limulus blood clot.

PMID- 14583530
TI  - Imprisonment in a death-row cell: the fates of microbes entrapped in the Limulus
      blood clot.

PMID- 14583531
TI  - A liposome-permeating activity from the surface of the carapace of the American
      horseshoe crab, Limulus polyphemus.

PMID- 14583532
TI  - Development and Characterization of a Self-Referencing Glutamate-Selective Micro
      biosensor.

PMID- 14583533
TI  - Zinc modulation of hemichannel currents in Xenopus oocytes.

PMID- 14583534
TI  - Transient use of tricaine to remove the telencephalon has no residual effects on
      physiological recordings of supramedullary/dorsal neurons of the cunner,
      Tautogolabrus adspersus.

PMID- 14583535
TI  - Zinc chelation enhances the sensitivity of the ERG b-wave in dark-adapted skate
      retina.

PMID- 14583536
TI  - Intracellular release of caged calcium in skate horizontal cells using fine
      optical fibers.

PMID- 14583537
TI  - Neural recordings from the lateral line in free-swimming toadfish, Opsanus tau.

PMID- 14583538
TI  - Memory reconsolidation in Hermissenda.

PMID- 14583540
TI  - Neurochemical modulation of behavioral response to chemical stimuli in Homarus
      americanus.

PMID- 14583539
TI  - Training alone, not the tripeptide RGD, modulates calexcitin in Hermissenda.

PMID- 14583541
TI  - Kin recognition in juvenile zebrafish (Danio rerio) based on olfactory cues.

PMID- 14583542
TI  - Mate choice in zebrafish (Danio rerio) analyzed with video-stimulus techniques.

PMID- 14583544
TI  - Scanning electron microscopy investigation of epizootic lobster shell disease in
      Homarus americanus.

PMID- 14583543
TI  - Expressed sequence tag analysis of genes expressed in the bay scallop, Argopecten
      irradians.

PMID- 14583545
TI  - Characterization of phosphorus-regulated genes in Trichodesmium spp.

PMID- 14583546
TI  - Molecular quantification of toxic Alexandrium fundyense in the Gulf of Maine.

PMID- 14583547
TI  - Description of Vibrio alginolyticus infection in cultured Sepia officinalis,
      Sepia apama, and Sepia pharaonis.

PMID- 14583548
TI  - Detection of Edwardsiella infections in Opsanus tau by polymerase chain reaction.

PMID- 14583549
TI  - Catalase in microsporidian spores before and during discharge.

PMID- 14583550
TI  - Growth of a salt marsh invertebrate on several species of marsh grass detritus.

PMID- 14583551
TI  - Patterns of sedimentation in a salt marsh-dominated estuary.

PMID- 14583552
TI  - Multiple approaches to tracing nitrogen loss in the West Falmouth wastewater
      plume.

PMID- 14583553
TI  - Nitrogen flux and speciation through the subterranean estuary of Waquoit Bay,
      Massachusetts.

PMID- 14583554
TI  - Radiochemical estimates of submarine groundwater discharge to Waquoit Bay,
      Massachusetts.

PMID- 14583555
TI  - Importance of metabolism in the development of salt marsh ponds.

PMID- 14583556
TI  - Transplantation and isotopic evidence of the relative effects of ambient and
      internal nutrient supply on the growth of Ulva lactuca.

PMID- 14583557
TI  - Relative influence of grazing and nutrient supply on growth of the green
      macroalga Ulva lactuca in estuaries of Waquoit Bay, Massachusetts.

PMID- 14583558
TI  - Stable isotopic assessment of site loyalty and relationships between size and
      trophic position of the Atlantic horseshoe crab, Limulus polyphemus, within Cape
      Cod estuaries.

PMID- 14583559
TI  - Incubation conditions of forest soil yielding maximum dissolved organic nitrogen
      concentrations and minimal residual nitrate.

PMID- 14583560
TI  - Building a database of historic land cover to detect landscape change.

PMID- 14583562
TI  - Early stages of osteoarthritis: the search for sensitive predictors.

PMID- 14583563
TI  - Glucocorticoids in the treatment of early and late RA.

PMID- 14583565
TI  - Mycobacterium malmoense infection of the knee.

PMID- 14583564
TI  - Use of localised gene transfer to develop new treatment strategies for the
      salivary component of Sjogren's syndrome.
AB  - Effective treatment for Sjogren's syndrome (SS) might be developed locally by
      introducing genes encoding cytokines, which are potentially anti-inflammatory, or
      by introducing a cDNA encoding a soluble form of a key cytokine receptor, which
      can act as an antagonist and decrease the availability of certain cytokines, such
      as soluble tumour necrosis factor alpha receptors. Currently, the preferred
      choice of viral vector for immunomodulatory gene transfer is recombinant adeno
      associated virus. The use of gene transfer to help determine the pathophysiology
      and to alter the course of the SS-like disease in the NOD mouse model can
      ultimately lead to the development of new treatments for managing the salivary
      component in patients with SS.

PMID- 14583566
TI  - Estimation of inflammation by Doppler ultrasound: quantitative changes after
      intra-articular treatment in rheumatoid arthritis.
AB  - OBJECTIVE: To evaluate the use of ultrasound, including quantitative Doppler
      analysis of synovial vascularisation, before and after intra-articular treatment
      with glucocorticosteroids in patients with rheumatoid arthritis (RA). METHODS: 51
      patients with RA were followed prospectively after an intra-articular
      glucocorticosteroid injection. Disease modifying antirheumatic drug treatment was
      kept unchanged and no further injections given in this observation period. At
      baseline, disease activity was estimated clinically by target join pain on a 100
      mm visual analogue scale, on which the target joint was scored 0-3 for swelling
      and tenderness, and by ultrasound measurements of grey scale pixels, colour
      Doppler pixels, and the spectral Doppler resistive index (RI) as indicators of
      synovial swelling and inflammation. After four weeks, the measurements were
      repeated on the same joint. An observer unaware of the sequence and patient
      number evaluated the ultrasound images. RESULTS: At one month follow up after the
      glucocorticosteroid injection, a marked decrease in the fraction of colour pixels
      was seen in 41/51 patients (Student's t test p<0.001). Correspondingly, the RI
      increased indicating a diminished flow to the synovium (Student's t test p<0.01).
      Both the fraction of colour pixels and the RI values corresponded with the
      clinical evaluation and with the subjective effect of the treatment. The synovial
      membrane volume estimated by total amount of pixels showed a significant decrease
      by 31% after treatment. CONCLUSION: Ultrasound-Doppler seems to be a promising
      tool for the estimation of synovial activity in arthritis. After intra-articular
      glucocorticosteroid, changes in RI and fraction of colour pixels may both be used
      as quantitative measurements of the blood flow.

PMID- 14583567
TI  - Beta irradiation decreases collagen type II synthesis and increases nitric oxide
      production and cell death in articular chondrocytes.
AB  - BACKGROUND: When synovitis is proved, intra-articularly injected beta emitting
      radionuclides like yttrium-90 ((90)Y) are used to treat the inflamed synovium.
      OBJECTIVE: To study the viability, matrix production, and NO production during or
      after (90)Y treatment of chondrocytes. METHODS: Monolayer, alginate, and explant
      cultures of primary bovine articular chondrocytes as well as synoviocytes were
      incubated with 0-3 MBq (90)Y/ml medium for four days from culture day 3 onwards.
      Cell viability was demonstrated by light and electron microscopy or by trypan
      blue or ethidium bromide/fluorescein diacetate staining, membrane integrity by
      measurement of lactate dehydrogenase (LDH) activity in the culture supernatants.
      Biosynthetic activity was demonstrated by incorporation of [(3)H]proline and
      immunocytochemical staining of collagen type II. NO production was measured with
      the Griess reagent. RESULTS: In chondrocyte and synoviocyte monolayer cultures
      radiation caused a dose dependent increase in cell death and membrane destruction
      within four days. In alginate and explant cultures, where proliferation is low,
      no significantly increased LDH activity was seen, and cell viability was
      approximately 100% for up to 14 days after irradiation. Collagen type II
      expression (alginate) and biosynthetic activity (alginate and explants) were
      decreased dose dependently while there was an increase in NO production. Light
      and electron microscopy data showed that five weeks after irradiation all cells
      in alginate and most cells in explants subjected to 3 MBq (90)Y/ml were dead,
      whereas after lower amounts of irradiation several morphologically intact cells
      were found. CONCLUSIONS: beta Irradiation may influence the long term maintenance
      of cartilage tissue or the aetiology of degenerative joint diseases.

PMID- 14583568
TI  - Development of radiographic changes of osteoarthritis in the "Chingford knee"
      reflects progression of disease or non-standardised positioning of the joint
      rather than incident disease.
AB  - OBJECTIVE: To ascertain the extent to which the "Chingford knee" (that is,
      contralateral knee of the middle aged, obese, female patient with unilateral knee
      osteoarthritis (OA)) is a high risk radiographically normal joint as opposed to a
      knee in which radiographic changes of OA would have been apparent in a more
      extensive radiographic examination. METHODS: Subjects were 180 obese women, aged
      45-64 years, with unilateral knee OA, based on the standing anteroposterior (AP)
      view. Subjects underwent a series of radiographic knee examinations: semiflexed
      AP, supine lateral, and Hughston (patellofemoral (PF)) views. Bony changes of OA
      were graded by consensus of two readers. Medial tibiofemoral joint space width
      was measured by digital image analysis. Knee pain was assessed by the WOMAC OA
      Index after washout of all OA pain drugs. RESULTS: Despite the absence of
      evidence of knee OA in the standing AP radiograph, only 32 knees (18%) were
      radiographically normal in all other views. Ninety four knees (52%) exhibited TF
      knee OA in the semiflexed AP and/or lateral view. PF OA was seen in 121 knees
      (67%). Subjects with PF OA reported more severe knee pain than those without PF
      OA (mean WOMAC scores 9.9 v 8.3, p<0.05). CONCLUSION: The Chingford knee is not a
      radiographically normal joint. The high rate of incidence of OA reported
      previously for this knee ( approximately 50% within two years) may also reflect
      progression of existing OA or changes in radioanatomical positioning at follow up
      that showed evidence of stable disease that was present at baseline.

PMID- 14583569
TI  - Myocardial perfusion scintigraphy and coronary disease risk factors in systemic
      lupus erythematosus.
AB  - OBJECTIVE: To evaluate the prevalence of myocardial perfusion abnormalities and
      the possible association between myocardial perfusion defects and traditional
      coronary artery disease (CAD) risk factors as well as systemic lupus
      erythematosus (SLE) related risk factors. PATIENTS AND METHODS: Female patients
      with SLE, disease duration >5 years, age 18-55 years, who had used steroids for
      at least one year were enrolled. Traditional CAD risk factors evaluated were
      arterial hypertension, diabetes mellitus, dyslipidaemia, postmenopausal status,
      smoking, obesity, and premature family CAD profile. Myocardial perfusion
      scintigraphy was evaluated by single photon emission computed tomography with
      technetium 99m-sestamibi at rest and after dipyridamole induced stress. RESULTS:
      Eight two female patients with SLE without angina pectoris with mean (SD) age 37
      (10) years, disease duration 127 (57) months, SLE Disease Activity Index (SLEDAI)
      score 6 (5), and SLICC/ACR-DI score 2 (2) were evaluated. Myocardial perfusion
      abnormalities were found in 23 patients (28%). The mean (SD) number of CAD risk
      factors was 2.2 (1.6). There was a significant positive correlation between age
      and number of CAD risk factors. Lower high density lipoprotein (HDL) cholesterol
      level showed a significant association with abnormal scintigraphy. Logistic
      regression analysis showed that lower HDL cholesterol level and diabetes mellitus
      were associated with myocardial perfusion abnormalities. Current vasculitis was
      also associated with abnormal scintigraphy. CONCLUSIONS: Lower HDL cholesterol
      level and diabetes mellitus have a significant influence on abnormal myocardial
      perfusion results found in asymptomatic patients with SLE. Current vasculitis was
      associated with abnormal myocardial scintigraphy. These data suggest that
      abnormal myocardial scintigraphy may be related to subclinical atherosclerosis.

PMID- 14583570
TI  - Risk factors for subclinical atherosclerosis in a prospective cohort of patients
      with systemic lupus erythematosus.
AB  - OBJECTIVE: To evaluate traditional and non-traditional risk factors for
      subclinical atherosclerosis in systemic lupus erythematosus (SLE). METHODS: A
      prospective cohort of 78 patients with SLE without overt atherosclerotic disease
      was studied. SLE clinical and laboratory parameters, disease activity and damage,
      treatment and traditional risk factors for atherosclerosis were evaluated. At
      baseline (T1) and after five years' follow up (T2), the serum levels of anti
      oxidised palmitoyl arachidonoyl phosphocholine (oxPAPC), anti-heat shock protein
      65, and anti-beta(2)-glycoprotein I antibodies and C reactive protein were
      tested. At T2, intima-media thickness (IMT) was measured using duplex carotid
      sonography. Thickened intima, plaque, mean IMT (m-IMT), and maximum IMT (M-IMT)
      were assessed. RESULTS: A thickened intima was seen in 22/78 (28%) patients and
      plaque in 13/78 (17%). M-IMT and m-IMT were (mean (SD)) 0.77 (0.34) mm and 0.55
      (0.15) mm, respectively. Patients with carotid abnormalities were significantly
      older, had higher blood pressure and total serum cholesterol levels, and had
      taken a higher prednisone cumulative dosage than those without any lesions. The
      carotid abnormalities were associated with renal disease and ECLAM >2 at T1, and
      with azathioprine treatment. In multivariate analysis, age and cumulative
      prednisone dose were associated with carotid abnormalities; age, hypertension,
      and anti-oxPAPC at T2 were correlated with higher M-IMT and m-IMT. CONCLUSIONS:
      In patients with SLE some non-traditional risk factors for atherosclerosis were
      identified, the most important of which was the cumulative prednisone dose. The
      role of some traditional risk factors, such as age and hypertension, was also
      confirmed. The predictive value of the new immunological and inflammatory markers
      of atherosclerosis seems to be masked by some disease related features.

PMID- 14583571
TI  - Effect of tumour necrosis factor alpha antagonists on serum transaminases and
      viraemia in patients with rheumatoid arthritis and chronic hepatitis C infection.
AB  - BACKGROUND: Tumour necrosis factor alpha (TNF alpha) antagonists are effective
      for the treatment of rheumatoid arthritis (RA), but concerns remain about the
      safety of these agents in the presence of chronic infections, including hepatitis
      C virus (HCV) infection. OBJECTIVE: To examine the influence of treatment with
      TNF alpha antagonists on levels of HCV viraemia and serum transaminases in
      patients with RA and HCV. METHODS: In a retrospective survey the course of 16 HCV
      infected patients with RA who had received the TNF alpha antagonists etanercept
      or infliximab was analysed. Eight additional patients with RA and HCV were also
      enrolled into a three month prospective trial of etanercept. Serum concentrations
      of albumin, alkaline phosphatase, aspartate aminotransferase, alanine
      aminotransferase, and HCV were followed. RESULTS: Viraemia was measured in 22
      patients receiving a TNF alpha antagonist at the start of treatment and after 1
      34 months (median 9 months follow up). Twenty four patients had serial tests of
      liver related enzymes and albumin. None of the differences between liver related
      tests at baseline and at follow up achieved significance (p>0.05). Similarly, the
      mean HCV measurement at 1-3, 4-6, 7-12, and 13-34 months did not differ
      significantly from baseline (p>0.05). CONCLUSION: In this study, liver related
      blood tests and HCV viral load measurements did not change substantially. These
      findings suggest that TNF alpha antagonists merit further study for the treatment
      of RA in HCV infected patients. Larger and longer term studies are still needed.

PMID- 14583572
TI  - Endothelial nitric oxide synthase gene polymorphisms in Behcet's disease and
      rheumatic diseases with vasculitis.
AB  - OBJECTIVE: To assess potential associations between Korean Behcet's disease (BD)
      or other rheumatic diseases with vasculitis and two polymorphisms of the
      endothelial nitric oxide synthase (eNOS) gene, which include the Glu298Asp
      polymorphism in exon 7 and a variable number of tandem repeats (VNTR)
      polymorphism in intron 4. METHODS: 65 patients with BD, 27 with rheumatic
      diseases with vasculitis, and 80 controls were studied. Analyses of the Glu298Asp
      polymorphism in exon 7 and VNTR polymorphism in intron 4 of the eNOS gene were
      made by the polymerase chain reaction (PCR)-restriction fragment length
      polymorphism technique and PCR genotyping, respectively. Additionally, HLA-B51
      typing was performed in the BD group and controls by a two step PCR sequence
      specific primers method. RESULTS: Significant differences in Glu298Asp genotype
      frequencies were found between the BD or vasculitis groups and the controls (BD
      group v controls: p(corr)=0.006; vasculitis group v controls: p<0.001). The
      Asp298 frequency was much higher in the BD and vasculitis groups than in the
      controls. Even after stratification of the BD group based on the results of HLA
      B51 testing, a significant association of the Glu298Asp polymorphism was still
      found (p=0.002, Mantel-Haenszel weighted odds ratio 4.3, 95% confidence interval
      1.7 to 10.9). Distribution of the genotype frequencies in two eNOS gene
      polymorphisms was similar in connective tissue diseases-associated vasculitis and
      primary vasculitic syndromes. In contrast, distribution of alleles and genotypes
      of VNTR polymorphism did not differ between BD or vasculitis groups and the
      controls. CONCLUSION: The Glu298Asp polymorphism in exon 7 of the eNOS gene seems
      to be a susceptibility gene for Korean BD and other rheumatic diseases.

PMID- 14583573
TI  - Prevalence and outcome in systemic sclerosis associated pulmonary arterial
      hypertension: application of a registry approach.
AB  - OBJECTIVE: To determine the prevalence of systemic sclerosis associated pulmonary
      arterial hypertension (SScPAH), evaluate outcome, and identify predictors of
      mortality in a large patient cohort. METHODS: A prospective four year follow up
      study of 794 patients (722 from our own unit and 72 referrals). All patients
      screened for PAH using a combination of echocardiography, lung function testing,
      and clinical assessment. Patients with suspected raised pulmonary artery systolic
      pressures of >35 mm Hg, carbon monoxide transfer factor (TLCO) <50% predicted, or
      a precipitous fall in TLCO >20% over a one year period with no pulmonary
      fibrosis, and patients with SSc with breathlessness with no pulmonary fibrosis
      found were investigated with right heart catheterisation. All patients with
      SScPAH were treated in accordance with current best practice. RESULTS: The
      prevalence of PAH was 12% (89/722) by right heart catheter. The survival was 81%,
      63%, and 56% at 1, 2, and 3 years from the diagnosis (in 89 patients from our own
      cohort and 59/72 referrals). Haemodynamic indices of right ventricular failure-
      raised mRAP (hazard ratio 21), raised mPAP (hazard ratio 20), and low CI (hazard
      ratio 11) predicted an adverse outcome There was no significant difference in
      survival between patients with SScPAH with (n=40) and without (n=108) pulmonary
      fibrosis (p=0.3). CONCLUSIONS: The prevalence of SScPAH in this cohort was
      similar to that of other catheter based studies and lower than that of previous
      echo based studies. The 148 patients with SScPAH actively treated had comparable
      outcomes to those of the cohorts with primary pulmonary hypertension. A high mRAP
      was the strongest haemodynamic predictor of mortality. To improve prognosis,
      future treatments need to be implemented at an earlier disease stage to prevent
      right ventricular decompensation.

PMID- 14583575
TI  - Socioeconomic status, occupation, and risk of hospitalisation due to coxarthrosis
      in Denmark 1981-99.
AB  - OBJECTIVES: To predict the relative risk and time trend in hospitalisation due to
      coxarthrosis (CA) among groups of different socioeconomic status and occupations
      in order to test existing aetiological hypotheses. METHODS: Four consecutive
      cohorts of all gainfully employed Danish men were followed up for CA.
      Standardised hospitalisation ratios (SHR) and time trends were calculated.
      RESULTS: Self employed men had an SHR due to CA of 140 (95% confidence interval
      (CI) 130 to 151) in 1994-99. It changed -1.2% (95% CI -2 to -0.4) annually from
      1981 to 1999. Self employed farmers had an SHR of 286 (95% CI 262 to 313) during
      1994-99, increasing 0.14% a year (95% CI -0.9 to 1.1) from 1981 to 1999.
      Unskilled men had an SHR of 121 (95% CI 113 to 130) in 1994-99. The SHR increased
      1.6% annually (95% CI 0.7 to 2.4) from 1981 to 1999. Employed agricultural
      workers had an SHR of 189 (95% CI 158 to 227) from 1994 to 1999. The SHR
      increased 3.7% annually (95% CI 1.2 to 6.2) from 1981 to 1999. CONCLUSIONS: The
      relative risk of hospitalisation due to CA was consistently high among farmers in
      four successive analyses spanning an 18 year period. The relative risks remained
      stable over time despite the fact that the number of farmers decreased. The risk
      increased among employed workers in agriculture and horticulture over that
      period, and an increased risk was also found among tractor drivers and a few
      other occupations.

PMID- 14583574
TI  - Matrix metalloproteinases-3, -8, -9 as markers of disease activity and joint
      damage progression in early rheumatoid arthritis.
AB  - OBJECTIVE: To analyse the relation between systemic levels of pro-MMP-3, -8, and 
      9 matrix metalloproteinase (MMP) activity in alpha(2) macroglobulin
      (alpha(2)M)/MMP complexes and the progression of joint destruction in patients
      with recent onset rheumatoid arthritis (RA). METHODS: 109 patients with RA of
      recent onset were entered into this longitudinal study. Patients were followed up
      for two years; clinical data, blood samples, and radiographs were obtained at
      baseline and at 1 and 2 years. Serum levels of MMPs were measured by sandwich
      ELISA and MMP activity assays. RESULTS: During the two years joint damage
      progressed from 0 to 10 (median Sharp score, p<0.001). Stable levels of pro-MMP-3
      and a significant decrease in the levels of pro-MMP-8 and -9 and alpha(2)M/MMP
      complexes were seen throughout the two years. Regression analysis showed that
      serum pro-MMP-3 levels at disease onset were independently associated with the
      progression of joint damage (B=0.7, 95% CI 0.3 to 1.1, p=0.001). Based on the
      rate of joint destruction, patients were divided into two subgroups: patients
      with mild and severe joint damage progression. The pro-MMP-3 levels were
      significantly higher in the group with severe compared with mild disease at all
      times. Levels of pro-MMP-8 and -9 were decreased in both groups, whereas
      alpha(2)M/MMP complex levels decreased in the group with mild disease only.
      CONCLUSION: Serum levels of the MMPs studied are associated with disease
      activity, but serum pro-MMP-3 levels at the onset of disease are also predictive
      of joint damage progression.

PMID- 14583577
TI  - Lymphocyte depletion with fludarabine in patients with psoriatic arthritis:
      clinical and immunological effects.
AB  - OBJECTIVE: To obtain preliminary information on the safety and efficacy of
      fludarabine in PsA and analyse its immunomodulatory effects in peripheral blood
      and synovial tissue. METHODS: 15 patients with active PsA who did not respond to
      DMARDs were randomly allocated to receive fludarabine every four weeks or
      placebo. Primary outcomes were the proportion of patients who met the ACR20 and
      the psoriatic arthritis response criteria (PsARC) at 16 weeks. Secondary outcomes
      were changes in tender or swollen joint counts and scores of the psoriasis area
      and severity index (PASI). Phenotypic analysis of peripheral blood mononuclear
      cells (PBMC), synovial immunohistochemistry, and functional analysis of PBMC were
      used to determine the immunomodulatory effects of fludarabine. RESULTS: At 16
      weeks the ACR20 criteria were met by 3/7 (43%) fludarabine treated v 0/8 placebo
      treated patients (p=0.08); the PsARC was achieved by 4/7 (57%) fludarabine
      treated v 2/8 (25%) placebo treated patients; and 3/7 (43%) fludarabine treated v
      0/7 placebo treated patients had > or =20% improvement in the PASI. Marked
      peripheral lymphopenia involving naive (CD4(+) CD45RA(+)) and memory (CD4(+)
      CD45RO(+)) T cells, CD8(+) T cells, and B cells was seen in fludarabine treated
      patients. CONCLUSIONS: In PsA fludarabine induces significant peripheral, but
      modest, synovial lymphopenia, and a trend towards improved clinical response.

PMID- 14583576
TI  - Anticardiolipin, anti-beta(2)-glycoprotein I and antiprothrombin antibodies in
      black South African patients with infectious disease.
AB  - OBJECTIVES: To investigate IgG, IgM, and IgA, antiphospholipid antibodies (aPL),
      against cardiolipin (aCL), beta(2)-glycoprotein I (anti-beta(2)GPI), and
      prothrombin (anti-PT), in black South African patients with infectious disease.
      Unlike patients with systemic lupus erythematosus (SLE) and the antiphospholipid
      syndrome (APS), raised levels of aPL in infectious diseases are not usually
      associated with thrombotic complications. PATIENTS AND METHODS: Serum samples
      from 272 patients with a variety of infectious diseases (100 HIV positive, 112
      leprosy, 25 syphilis, 25 malaria, and 10 HCV patients) were studied and compared
      with autoantibody levels in 100 normal controls. All three aPL were measured
      using commercial enzyme linked immunosorbent assay (ELISA) kits. RESULTS: Raised
      levels of all three aPL were found in all patient groups studied: aCL in 7%, anti
      beta(2)GPI in 6%, and aPT in 43% of 100 HIV patients, in 29%, 89%, and 21% of 112
      patients with leprosy, in 8%, 8%, and 28% of 25 patients with syphilis, in 12%,
      8%, and 28% of 25 patients with malaria, and in 20%, 30%, and 30% of 10 HCV
      patients studied, respectively. CONCLUSIONS: The prevalence of aCL and anti
      beta(2)GPI in black South African HIV positive patients, or those with syphilis,
      malaria, or hepatitis C virus is lower than reported for mixed race or white
      populations. aPT were the most prevalent aPL detected in these patient groups,
      except in patients with leprosy, for whom anti-beta(2)GPI was the most prevalent,
      and where the spectrum of aPL was similar to that seen in patients with SLE and
      APS.

PMID- 14583578
TI  - Experience with infliximab (anti-TNF alpha monoclonal antibody) as monotherapy
      for giant cell arteritis.

PMID- 14583579
TI  - Correlation between interleukin 10 gene promoter region polymorphisms and
      clinical manifestations in Japanese patients with Sjogren's syndrome.

PMID- 14583580
TI  - Cigarette smoking, TB, and TNF inhibitors.

PMID- 14583581
TI  - Large synovial cysts originating from the sternoclavicular joints in a patient
      with rheumatoid arthritis.

PMID- 14583582
TI  - Cyclosporin A in rheumatoid arthritis.

PMID- 14583583
TI  - Cyclosporin and methotrexate therapy.

PMID- 14583584
TI  - Low dose methotrexate osteopathy in a patient with polyarticular juvenile
      idiopathic arthritis.

PMID- 14583585
TI  - Is methotrexate osteopathy a form of bone idiosyncrasy?

PMID- 14583586
TI  - Clinical comparisons of RA between different populations: are they feasible?

PMID- 14583588
TI  - Microarray analysis in drug discovery: an uplifting view of depression.
AB  - Genomic profiling provides insights into drug evaluation for diseases without
      defined molecular mechanisms or cellular assays. Levy provides a brief background
      in the development of microarray analysis and discussion of the application of
      this technique to pharmacogenomics. Highlighted is the microarray analysis of
      primary human neurons treated with antidepressants, antipsychotics, or opioid
      receptor agonists, demonstrating that these classes of drugs can be properly
      categorized by using two different statistical analysis methods: classification
      tree and random forest. Not only is microarray analysis valuable for drug
      evaluation and leading candidate development, but the genes identified as markers
      for the various drug classifications point to new directions for research into
      the underlying pathways responsible for human diseases, such as depression and
      psychosis.

PMID- 14583589
TI  - Therapeutic potential of antisense nucleic acid molecules.
AB  - Elucidation of many disease-related signal transduction and gene expression
      pathways has provided unparalleled opportunities for the development of targeted
      therapeutics. The types of molecules in development are increasingly varied and
      include small-molecule enzyme inhibitors, humanized antibodies to cell surface
      receptors, and antisense nucleic acids for silencing the expression of specific
      genes. This Perspective reviews the basis for various antisense strategies for
      modulating gene expression, including RNA interference, and discusses the
      prospects for their clinical use.

PMID- 14583590
TI  - The homodimer of prostate-specific membrane antigen is a functional target for
      cancer therapy.
AB  - Prostate-specific membrane antigen (PSMA) is a type 2 integral membrane
      glycoprotein that serves as an attractive target for cancer immunotherapy by
      virtue of its abundant and restricted expression on the surface of prostate
      carcinomas and the neovasculature of most other solid tumors. However, relatively
      little is known about the molecular structure of this target. Here, we report
      that PSMA is expressed on tumor cells as a noncovalent homodimer. A truncated
      PSMA protein, lacking transmembrane and cytoplasmic domains, also formed
      homodimers, indicating that the extracellular domain is sufficient for
      dimerization. PSMA dimers but not monomers displayed a native conformation and
      possessed high-level carboxypeptidase activity. A unique dimer-specific epitope
      was identified by using one of a panel of novel mAbs. When used to immunize
      animals, dimer but not monomer elicited antibodies that efficiently recognized
      PSMA-expressing tumor cells. These findings on PSMA structure and biology may
      have important implications for active and passive immunotherapy of prostate and
      other cancers.

PMID- 14583591
TI  - Positional cloning of the major quantitative trait locus underlying lung tumor
      susceptibility in mice.
AB  - Pulmonary adenoma susceptibility 1 (Pas1), located on chromosome 6, is the major
      locus affecting inherited predisposition to lung tumor development in mice. We
      have fine mapped the Pas1 locus to a region of approximately 0.5 megabases by
      using congenic strains of mice, constructed by placing the Pas1 region of
      chromosome 6 from A/J mice onto the genetic background of C57BL/6J mice.
      Systematic characterization of Pas1 candidates establishes the Las1 (lung adenoma
      susceptibility 1) and Kras2 (Kirsten rat sarcoma oncogene 2) genes as primary
      candidates for the Pas1 locus. Clearly, Kras2 affects lung tumor progression
      only, and Las1 is likely to affect lung tumor multiplicity.

PMID- 14583592
TI  - Identification of the protein kinase A regulatory RIalpha-catalytic subunit
      interface by amide H/2H exchange and protein docking.
AB  - An important goal after structural genomics is to build up the structures of
      higher-order protein-protein complexes from structures of the individual
      subunits. Often structures of higher order complexes are difficult to obtain by
      crystallography. We have used an alternative approach in which the structures of
      the individual catalytic (C) subunit and RIalpha regulatory (R) subunit of PKA
      were first subjected to computational docking, and the top 100,000 solutions were
      subsequently filtered based on amide hydrogen/deuterium (H/2H) exchange interface
      protection data. The resulting set of filtered solutions forms an ensemble of
      structures in which, besides the inhibitor peptide binding site, a flat interface
      between the C-terminal lobe of the C-subunit and the A- and B-helices of RIalpha
      is uniquely identified. This holoenzyme structure satisfies all previous
      experimental data on the complex and allows prediction of new contacts between
      the two subunits.

PMID- 14583593
TI  - Visualizing the distribution and transport of mRNAs in living cells.
AB  - We have visualized the movements of native mRNAs in living cells. Using nuclease
      resistant molecular beacons, we imaged the transport and localization of oskar
      mRNA in Drosophila melanogaster oocytes. When the localization pattern was
      altered by genetic manipulation of the mRNA's 3' untranslated region, or by
      chemical perturbation of the intracellular tubulin network, the distribution of
      the fluorescence signals changed accordingly. We tracked the migration of oskar
      mRNA in real time, from the nurse cells where it is produced to the posterior
      cortex of the oocyte where it is localized. Our observations reveal the presence
      of a transient, and heretofore elusive, stage in the transport of oskar mRNA.
      Direct visualization of specific mRNAs in living cells with molecular beacons
      will accelerate studies of intracellular RNA trafficking and localization, just
      as the use of green fluorescent protein has stimulated the study of specific
      proteins in vivo.

PMID- 14583594
TI  - Revealing competitive Forster-type resonance energy-transfer pathways in single
      bichromophoric molecules.
AB  - We demonstrate measurements of the efficiency of competing Forster-type energy
      transfer pathways in single bichromophoric systems by monitoring simultaneously
      the fluorescence intensity, fluorescence lifetime, and the number of independent
      emitters with time. Peryleneimide end-capped fluorene trimers, hexamers, and
      polymers with interchromophore distances of 3.4, 5.9, and on average 42 nm,
      respectively, served as bichromophoric systems. Because of different energy
      transfer efficiencies, variations in the interchromophore distance enable the
      switching between homo-energy transfer (energy hopping), singlet-singlet
      annihilation, and singlet-triplet annihilation. The data suggest that similar
      energy-transfer pathways have to be considered in the analysis of single-molecule
      trajectories of donor/acceptor pairs as well as in natural and synthetic
      multichromophoric systems such as light-harvesting antennas, oligomeric
      fluorescent proteins, and dendrimers. Here we report selectively visualization of
      different energy-transfer pathways taking place between identical fluorophores in
      individual bichromophoric molecules.

PMID- 14583595
TI  - Microarray analysis of gene expression in blood neutrophils of parturient cows.
AB  - It is well documented that blood neutrophils from parturient dairy cows do not
      perform as well as neutrophils from nonparturient cows in laboratory assays of
      adhesion, migration, or phagocytosis-induced respiratory burst. However, little
      is known about the possible molecular basis for parturition-induced changes in
      neutrophils. cDNA microarray analysis was used in the current study to explore
      parturition-induced changes in gene expression profiles in bovine blood
      neutrophils. Total RNA from isolated blood neutrophils of four parturient
      Holstein cows was obtained before, during, and after parturition, reverse
      transcribed into cDNA, and sequentially labeled with Cy3 or Cy5 dyes prior to
      paired hybridizations to 1,056 member bovine total leukocyte (BOTL-3) microarrays
      in a loop design. Resulting gene expression data were LOWESS normalized by array
      and analyzed using a mixed model approach. Results showed that expression
      profiles for 302 BOTL-3 genes were influenced by parturition. BLASTn analysis and
      preliminary clustering of affected genes by biological function indicated that
      the largest proportion (14%) of changed genes encode proteins critical to
      regulation of apoptosis. Independent confirmation of altered expression for 16 of
      these genes was achieved using quantitative real-time RT-PCR (Q-RT-PCR). A
      predominantly survival phenotype inferred from the microarray and Q-RT-PCR
      results was substantiated by monitoring apoptosis status of blood neutrophils
      from castrated male cattle cultured in the presence of sera from parturient cows.
      Thus our combined gene expression and apoptosis phenotyping results suggest that
      bovine parturition may induce prolonged survival in normally short-lived blood
      neutrophils.

PMID- 14583596
TI  - Gene expression profile analysis of 4-phenylbutyrate treatment of IB3-1 bronchial
      epithelial cell line demonstrates a major influence on heat-shock proteins.
AB  - Most individuals with cystic fibrosis (CF) carry one or two mutations that result
      in a maturation defect of the full-length CFTR protein. The DeltaF508 mutation
      results in a mutant protein that is degraded by the proteosome instead of
      progressing to the apical membrane where it functions as a cAMP-regulated
      chloride channel. 4-Phenylbutyrate (PBA) modulates heat-shock protein expression
      and promotes trafficking of DeltaF508, thus permitting maturation and membrane
      insertion. The goal of this study was to gain insight into the genetic mechanism
      of PBA action through a large-scale analysis of gene expression. The Affymetrix
      genome-spanning U133 microarray set was used to compare mRNA expression levels in
      untreated IB3-1 cell line cultures with cultures treated with 1 mM PBA for 12 and
      24 h. The most notable changes in mRNA levels were transient elevations in heat
      shock proteins. The majority of genes downregulated throughout the application
      period were functionally associated with control of gene expression. Another set
      of genes increased in expression starting at 24 h, suggesting these are
      downstream effects of altered gene expression initiated by PBA. More than one
      third of the genes in this late expressing set were identified as having
      potential significance in understanding the pathology of CF. Our results
      demonstrate the usefulness of gene expression profile analysis in understanding
      the consequences of PBA treatment and provide insights in how this drug exerts
      its effect on the trafficking of CFTR.

PMID- 14583597
TI  - A survey of genetic and epigenetic variation affecting human gene expression.
AB  - The identification of human sequence polymorphisms that regulate gene expression
      is key to understanding human genetic diseases. We report a survey of human genes
      that demonstrate allelic differences in gene expression, reflecting the presence
      of putative allele-specific cis-acting factors of either genetic or epigenetic
      nature. The expression of allelic transcripts in heterozygous samples is assessed
      directly by relative quantitation of intragenic marker alleles in messenger or
      heteronuclear RNA derived from cells or tissues. This survey used 193 single
      nucleotide polymorphisms (SNPs) from 129 genes expressed in lymphoblastoid cell
      lines, to identify 23 genes (18%) with common allele-specific transcripts whose
      expression deviated from the expected equimolar ratio. A subset of these
      deviations, or "allelic imbalances," can be observed in multiple samples derived
      from reference CEPH ("Centre d'Etude du Polymorphisme Humain") pedigrees and
      demonstrate a spectrum of patterns of transmission, including cosegregation of
      allelic skewing across generations compatible with Mendelian inheritance as well
      as random monoallelic expression for three genes (IL1A, HTR2A, and FGB).
      Additional studies for BTN3A2 provide evidence of SNPs and haplotypes in complete
      linkage disequilibrium with high- and low-expressing transcripts. The pipeline
      described herein offers tools for efficient identification and characterization
      of allelic expression allowing identification of regulatory sequence variants as
      well as epigenetic variation affecting human gene expression.

PMID- 14583598
TI  - Pancreatic triacylglycerol lipase in a hibernating mammal. I. Novel genomic
      organization.
AB  - Pancreatic triacylglycerol lipase (PTL) is expressed in novel locations during
      hibernation in the thirteen-lined ground squirrel (Spermophilus
      tridecemlineatus). PTL cDNAs isolated from two of these locations, heart and
      white adipose tissue (WAT), contain divergent 5'-untranslated regions (5'-UTRs)
      suggesting alternative promoter usage or the possibility of multiple PTL genes in
      the ground squirrel genome. In addition, cDNAs isolated from WAT contain tracts
      of retroviral sequence in their 5'-UTRs. Our examination of PTL genomic clones
      isolated from a thirteen-lined ground squirrel genomic DNA library, coupled with
      genomic Southern blot analysis, enabled us to conclude that PTL mRNAs expressed
      in heart and WAT are the products of the same single-copy gene. The 5' portion of
      this gene spans 9.2 kb, is composed of 6 exons, and contains a full-length
      endogenous retroviral genome with conserved long terminal repeats (LTRs).
      Alignment of the ground squirrel PTL gene with the mouse, rat, and human PTL
      genes indicates that this retrovirus inserted into the ground squirrel genome
      approximately 200 bases upstream of the original PTL transcriptional start site.
      The insertion is a relatively recent event based on largely intact open-reading
      frames containing minimal frame-shift and nonsense mutations. The high-percentage
      identity (99.2%) shared between the 5'- and 3'-LTRs of this endogenous retrovirus
      suggests that the insertion occurred as recently as 300,000 years ago.

PMID- 14583599
TI  - Pancreatic triacylglycerol lipase in a hibernating mammal. II. Cold-adapted
      function and differential expression.
AB  - Thirteen-lined ground squirrels (Spermophilus tridecemlineatus) exploit the low
      temperature activity of pancreatic triacylglycerol lipase (PTL) during
      hibernation. Lipolytic activity at body temperatures associated with hibernation
      was examined using recombinant ground squirrel and human PTLs expressed in yeast.
      Both the human and ground squirrel enzymes displayed high activity at
      temperatures as low as 0 degrees C and showed Q10 values of 1.2-1.5 over a range
      of 37-7 degrees C. These studies indicate that low-temperature lipolysis is a
      general property of PTL and does not require protein modifications unique to
      mammalian cells and/or the hibernating state. Western blots show elevated levels
      of PTL protein during hibernation in both heart and white adipose tissue (WAT).
      Significant increases in PTL gene expression are seen in heart, WAT, and testes;
      but not in pancreas, where PTL mRNA levels are highest. Upregulation of PTL in
      testes is also accompanied by expression of the PTL-specific cofactor, colipase.
      The multi-tissue expression of PTL during hibernation supports its role as a key
      enzyme that shows high activity at low temperatures.

PMID- 14583600
TI  - Differential role of MEK5alpha and MEK5beta in BMK1/ERK5 activation.
AB  - Big mitogen-activated protein kinase 1/extracellular-regulated kinase 5
      (BMK1/ERK5) is regulated sequentially by a series of upstream MAP kinase kinases
      (MEKs) in a signaling cascade. MEKs activate their downstream MAPK by
      phosphorylation of threonine and tyrosine in the T- X-Y motif. MEK5 is the
      upstream BMK1 kinase and exists as naturally occurring splice variants, MEK5alpha
      and MEK5beta. The full-length MEK5 (MEK5alpha) is 89 amino acids longer than
      MEK5beta at the N terminus, but the precise functional difference between the two
      splice variants is not known. Dual phosphorylation site mutation of MEK5alpha
      (Ser-311 --> Asp and Thr- 315 --> Asp; MEK5alpha(S311D/T315D)) activated BMK1,
      but the corresponding dual phosphorylation sites mutant of MEK5beta could not
      induce BMK1 kinase activation or nuclear translocation. Furthermore, MEK5beta
      inhibited epidermal growth factor-induced BMK1 activation and
      MEK5alpha(S311D/T315D)-induced MEF2 transcriptional activity. Both MEK5alpha and
      MEK5beta individually co-immunoprecipitated with BMK1, but the presence of
      MEK5beta prevented association of MEK5alpha with BMK1 suggesting a mechanistic
      basis for the dominant-negative behavior of MEK5beta on BMK1 activation. The
      ratio of MEK5alpha to MEK5beta expression was higher in cancer cell lines, and
      overexpression of MEK5beta-inhibited serum-induced DNA synthesis. These data
      suggest that alternative splicing of MEK5alpha and MEK5beta may play a critical
      role in BMK1 activation and subsequent cell proliferation.

PMID- 14583601
TI  - The protein kinase SOS2 activates the Arabidopsis H(+)/Ca(2+) antiporter CAX1 to
      integrate calcium transport and salt tolerance.
AB  - The regulation of ions within cells is an indispensable component of growth and
      adaptation. The plant SOS2 protein kinase and its associated Ca(2+) sensor, SOS3,
      have been demonstrated to modulate the plasma membrane H(+)/Na(+) antiporter
      SOS1; however, how these regulators modulate Ca(2+) levels within cells is poorly
      understood. Here we demonstrate that SOS2 regulates the vacuolar H(+)/Ca(2+)
      antiporter CAX1. Using a yeast growth assay, co-expression of SOS2 specifically
      activated CAX1, whereas SOS3 did not. CAX1-like chimeric transporters were
      activated by SOS2 if the chimeric proteins contained the N terminus of CAX1.
      Vacuolar membranes from CAX1-expressing cells were made to be H(+)/Ca(2+)
      competent by the addition of SOS2 protein in a dose-dependent manner. Using a
      yeast two-hybrid assay, SOS2 interacted with the N terminus of CAX1. In each of
      these yeast assays, the activation of CAX1 by SOS2 was SOS3-independent. In
      planta, the high level of expression of a deregulated version of CAX1 caused salt
      sensitivity. These findings suggest multiple functions for SOS2 and provide a
      mechanistic link between Ca(2+) and Na(+) homeostasis in plants.

PMID- 14583602
TI  - Identification of a human cytoplasmic poly(A) nuclease complex stimulated by
      poly(A)-binding protein.
AB  - The poly(A) tail shortening in mRNA, called deadenylation, is the first rate
      limiting step in eukaryotic mRNA turnover, and the polyadenylate-binding protein
      (PABP) appears to be involved in the regulation of this step. However, the
      precise role of PABP remains largely unknown in higher eukaryotes. Here we
      identified and characterized a human PABP-dependent poly(A) nuclease (hPAN)
      complex consisting of catalytic hPan2 and regulatory hPan3 subunits. hPan2 has
      intrinsically a 3' to 5' exoribonuclease activity and requires Mg2+ for the
      enzyme activity. On the other hand, hPan3 interacts with PABP to simulate hPan2
      nuclease activity. Interestingly, the hPAN nuclease complex has a higher
      substrate specificity to poly(A) RNA upon its association with PABP. Consistent
      with the roles of hPan2 and hPan3 in mRNA decay, the two subunits exhibit
      cytoplasmic co-localization. Thus, the human PAN complex is a poly(A)-specific
      exoribonuclease that is stimulated by PABP in the cytoplasm.

PMID- 14583603
TI  - The transducer domain is important for clamp operation in human DNA topoisomerase
      IIalpha.
AB  - DNA topoisomerase II is a multidomain homodimeric enzyme that changes DNA
      topology by coupling ATP hydrolysis to the transport of one DNA helix through a
      transient double-stranded break in another. The process requires dramatic
      conformational changes including closure of an ATP-operated clamp, which is
      comprised of two N-terminal domains from each protomer. The most N-terminal
      domain contains the ATP-binding site and is directly involved in clamp closure,
      undergoing dimerization upon ATP binding. The second domain, the transducer
      domain, forms the walls of the N-terminal clamp and connects the clamp to the
      enzyme core. Although structurally conserved, it is unclear whether the
      transducer domain is involved in clamp mechanism. We have purified and
      characterized a human topoisomerase II alpha enzyme with a two-amino acid
      insertion at position 408 in the transducer domain. The enzyme retains both
      ATPase and DNA cleavage activities. However, the insertion, which is situated far
      from the N-terminal dimerization area, severely disrupts the function of the N
      terminal clamp. The clamp-deficient enzyme is catalytically inactive and lacks
      most aspects of interdomain communication. Surprisingly, it seems to have
      retained the intersubunit communication, allowing it to bind ATP cooperatively in
      the presence of DNA. The results show that even distal parts of the transducer
      domain are important for the dynamics of the N-terminal clamp and furthermore
      indicate that stable clamp closure is not required for cooperative binding of
      ATP.

PMID- 14583604
TI  - Cloning and expression of cDNA for a luciferase from the marine copepod Metridia
      longa. A novel secreted bioluminescent reporter enzyme.
AB  - Metridia longa is a marine copepod from which a blue bioluminescence originates
      as a secretion from epidermal glands in response to various stimuli. We
      demonstrate that Metridia luciferase is specific for coelenterazine to produce
      blue light (lambda(max) = 480 nm). Using an expression cDNA library and
      functional screening, we cloned and sequenced the cDNA encoding the Metridia
      luciferase. The cDNA is an 897-bp fragment with a 656-bp open reading frame,
      which encodes a 219-amino acid polypeptide with a molecular weight of 23,885. The
      polypeptide contains an N-terminal signal peptide of 17 amino acid residues for
      secretion. On expression of the Metridia luciferase gene in mammalian Chinese
      hamster ovary cells the luciferase is detected in the culture medium confirming
      the existence of a naturally occurring signal peptide for secretion in the cloned
      luciferase. The novel secreted luciferase was tested in a practical assay
      application in which the activity of A2a and NPY2 G-protein-coupled receptors was
      detected. These results clearly suggest that the secreted Metridia luciferase is
      well suited as a reporter for monitoring gene expression and, in particular, for
      the development of novel ultrahigh throughput screening technologies.

PMID- 14583605
TI  - The elusive role of the potential factor X cation-binding exosite-1 in substrate
      and inhibitor interactions.
AB  - A number of studies suggest that blood-clotting factor X (FX) uses secondary
      site(s) to interact (as a substrate) with its activators. Numerous pieces of
      evidence also imply that, within prothrombinase (as an enzyme), activated FX
      (FXa) uses exosite(s) for cofactor Va and/or prothrombin recognition. Similarly,
      FXa exosite(s) seem to govern interaction with inhibitors. An obvious difference
      between FXa and thrombin resides within a region called exosite-1: positively
      charged in thrombin and clearly of opposite polarity in FXa. To investigate the
      role of this potential cation-binding exosite, we prepared a series of mutants
      within loops 34-40 and 70-80 of FX. Overall, the mutations induced relatively
      subtle, non-synergistic modulation. The potential exosite was dispensable for FX
      activation and is unlikely to constitute a critical region for factor Va binding,
      albeit it is clearly important for prothrombin activation. Our data also
      implicate loop 34-40 of FXa in the interaction with the tissue factor pathway
      inhibitor, in prevention of plasminogen activator inhibitor-1 binding, and in
      tempering inhibition by heparin-activated antithrombin. Compared with FX, mutants
      with reduced electrostatic potential potentiated thrombin production in FX
      depleted plasma, whereas mutants with inverted electrostatic potential impeded
      clotting. Despite the definite consequences observed, disruption of the potential
      cation-binding exosite of FX had rather weak effects, far from what would be
      expected if this region was as crucial as in thrombin.

PMID- 14583606
TI  - Three novel Bid proteins generated by alternative splicing of the human Bid gene.
AB  - Bid, a BH3-only Bcl-2 protein, is activated by proteolytic cleavage exposing the
      BH3 domain, which then induces apoptosis by interacting with pro-apoptotic Bcl-2
      family proteins (e.g. Bax and Bak) at the mitochondrial surface. The arrangement
      of domains within Bid suggested that Bid function might be regulated in part by
      alternative splicing. We have determined the gene structure of human Bid and
      identified a number of novel exons. We have also demonstrated endogenous mRNA and
      protein expression for three novel isoforms of Bid, generated using these exons.
      Bid(S) contains the N-terminal regulatory domains of Bid without the BH3 domain;
      Bid(EL) corresponds to full-length Bid with additional N-terminal sequence; and
      Bid(ES) contains only the Bid sequence downstream of the BH3 domain. Expression
      of these isoforms is regulated during granulocyte maturation. In functional
      studies Bid(EL) induces apoptosis, whereas Bid(S) abrogates the pro-apoptotic
      effects of truncated Bid and inhibits Fas-mediated apoptosis. Bid(ES) induces
      apoptosis but is also able to partially inhibit the pro-apoptotic effects of
      truncated Bid. These three novel endogenously expressed isoforms of Bid are
      distinct in their expression, their cellular localization, and their effects upon
      cellular apoptosis. Differential expression of these novel Bid isoforms may
      regulate the function of Bid following cleavage and thus influence the fate of
      cells exposed to a range of pro-apoptotic stimuli.

PMID- 14583607
TI  - The structure of the AXH domain of spinocerebellar ataxin-1.
AB  - Spinocerebellar ataxia type 1 is a late-onset neurodegenerative disease caused by
      the expansion of a CAG triplet repeat in the SCA1 gene. This results in the
      lengthening of a polyglutamine tract in the gene product ataxin-1. This produces
      a toxic gain of function that results in specific neuronal death. A region in
      ataxin-1, the AXH domain, exhibits significant sequence similarity to the
      transcription factor HBP1. This region of the protein has been implicated in RNA
      binding and self-association. We have determined the crystal structure of the AXH
      domain of ataxin-1. The AXH domain is dimeric and contains an OB-fold, a
      structural motif found in many oligonucleotide-binding proteins, supporting its
      proposed role in RNA binding. By structure comparison with other proteins that
      contain an OB-fold, a putative RNA-binding site has been identified. We also
      identified a cluster of charged surface residues that are well conserved among
      AXH domains. These residues may constitute a second ligand-binding surface,
      suggesting that all AXH domains interact with a common yet unidentified partner.

PMID- 14583608
TI  - Peptidoglycan recognition proteins involved in 1,3-beta-D-glucan-dependent
      prophenoloxidase activation system of insect.
AB  - The prophenoloxidase (proPO) cascade is a major innate immune response in
      invertebrates, which is triggered into its active form by elicitors, such as
      lipopolysaccharide, peptidoglycan, and 1,3-beta-D-glucan. A key question of the
      proPO system is how pattern recognition proteins recognize pathogenic microbes
      and subsequently activate the system. To investigate the biological function of
      1,3-beta-D-glucan pattern recognition protein in the proPO cascade system, we
      isolated eight different 1,3-beta-D-glucan-binding proteins from the hemolymph of
      large beetle (Holotrichia diomphalia) larvae by using 1,3-beta-D-glucan
      immobilized column. Among them, a 20- and 17-kDa protein (referred to as Hd-PGRP
      1 and Hd-PGRP-2) show high sequence identity with the short forms of
      peptidoglycan recognition proteins (PGRPs-S) from human and Drosophila
      melanogaster. To be able to characterize the biochemical properties of these two
      proteins, we expressed them in Drosophila S2 cells. Hd-PGRP-1 and Hd-PGRP-2 were
      found to specifically bind both 1,3-beta-D-glucan and peptidoglycan. By BIAcore
      analysis, the minimal 1,3-beta-D-glucan structure required for binding to Hd-PGRP
      1 was found to be laminaritetraose. Hd-PGRP-1 increased serine protease activity
      upon binding to 1,3-beta-D-glucan and subsequently induced the phenoloxidase
      activity in the presence of both 1,3-beta-D-glucan and Ca(2+), but no
      phenoloxidase activity was elicited under the same conditions in the presence of
      peptidoglycan and Ca(2+). These results demonstrate that Hd-PGRP-1 can serve as a
      receptor for 1,3-beta-D-glucan in the insect proPO activation system.

PMID- 14583609
TI  - The anti-apoptotic effect of Notch-1 requires p56lck-dependent, Akt/PKB-mediated
      signaling in T cells.
AB  - The Notch family of transmembrane receptors have been implicated in a variety of
      cellular decisions in different cell types. Here we investigate the mechanism
      underlying Notch-1-mediated anti-apoptotic function in T cells using model cell
      lines as the experimental system. Ectopic expression of the intracellular domain
      of Notch-1/activated Notch (AcN1) increases expression of anti-apoptotic proteins
      of the inhibitors of apoptosis (IAP) family, the Bcl-2 family, and the FLICE-like
      inhibitor protein (FLIP) and inhibits death triggered by multiple stimuli that
      activate intrinsic or extrinsic pathways of apoptosis in human and murine T cell
      lines. Numb inhibited the AcN1-dependent induction of anti-apoptotic proteins and
      anti-apoptotic function. Using pharmacological inhibitors and dominant-negative
      approaches, we describe a functional role for phosphatidylinositol 3-kinase
      (PI3K)-dependent activation of the serine-threonine kinase Akt/PKB in the
      regulation of AcN1-mediated anti-apoptotic function and the expression of FLIP
      and IAP family proteins. Using a cell line deficient for the T cell-specific, Src
      family protein, the tyrosine kinase p56(lck) and by reconstitution approaches we
      demonstrate that p56(lck) is required for the Notch-1-mediated activation of
      Akt/PKB function. Furthermore, the Src tyrosine kinase inhibitor, PP2, abrogated
      ectopically expressed AcN1-mediated anti-apoptotic function and phosphorylation
      of p56(lck). We present evidence that endogenous Notch-1 associates with p56(lck)
      and PI3K but that Akt/PKB does not co-immunoprecipitate with the
      Notch1.p56(lck).PI3K complex. Finally, we demonstrate that the
      Notch1.p56(lck).PI3K complex is present in primary T cells that have been
      activated in vitro and sustained in culture with the cytokine interleukin-2.

PMID- 14583611
TI  - Molecular chaperone Hsp90 associates with resistance protein N and its signaling
      proteins SGT1 and Rar1 to modulate an innate immune response in plants.
AB  - SGT1 and Rar1 are important signaling components of resistance (R) gene-mediated
      plant innate immune responses. Here we report that SGT1 and Rar1 associate with
      the molecular chaperone Hsp90. In addition, we show that Hsp90 associates with
      the resistance protein N that confers resistance to tobacco mosaic virus. This
      suggests that Hsp90-SGT1-Rar1 and R proteins might exist in one complex.
      Suppression of Hsp90 in Nicotiana benthamiana plants shows that it plays an
      important role in plant growth and development. In addition, Hsp90 suppression in
      NN plants compromises N-mediated resistance to tobacco mosaic virus. Our results
      reveal a new role for SGT1- and Rar1-associated chaperone machinery in R gene
      mediated defense signaling.

PMID- 14583610
TI  - N-terminal extension of canine glutamine synthetase created by splicing alters
      its enzymatic property.
AB  - It was found that an extra exon exists in the first intron of glutamine
      synthetase gene, generated by means of alternative splicing. Inclusion of this
      exon decreased the translation of glutamine synthetase (GS) in human, dog, and
      mouse. When translated in vitro with the canine GS transcript containing the
      exon, we obtained two different species of GS enzymes. Besides the known 45-kDa
      protein, the extended form of GS was identified with additional 40 amino acids on
      its N-terminal end. An upstream ATG in the extra exon served as a translation
      initiator for the long form of GS. When the long transcript was translated in
      vivo in animal cells, only the long GS was expressed. On the other hand, the long
      GS is less predominant relative to the short one in canine tissues including
      brain and liver. Subcellular fractionation of canine brain revealed that the long
      GS is present in all cellular compartments as is the short one, which is
      consistent with fluorescence microscopy data obtained with green fluorescent
      protein fused to GS. The short (SGS) and long (LGS) forms of canine GS were
      purified in Escherichia coli and shown to have similar Km values for l-glutamate
      and hydroxylamine. However, the Km values for ATP were slightly altered, 1.3 and
      1.9 mm for the short and long GSs, respectively. The Kis for l-methionine-S
      sulfoximine (MSOX), a highly potent ATP-dependent inactivator of GS, were
      considerably different such that the values are 0.067 and 0.124 mm for the short
      and long forms, respectively. When the intrinsic fluorescences of tryptophans
      were monitored upon bindings of chloride and metal ions without any effect on the
      oligomeric state, the pattern of quenching in LGS was significantly different
      from that of SGS. Taken together, the N-terminal extension in the long isoform of
      GS induces a conformational change of core enzyme, leading to a change in
      affinity to its substrates as well as in the effector-induced conformational
      alterations.

PMID- 14583612
TI  - Crystal structure of the homolog of the oncoprotein gankyrin, an interactor of Rb
      and CDK4/6.
AB  - The oncoprotein gankyrin plays a central role in tumorigenesis and cell
      proliferation. Gankyrin interacts with the retinoblastoma tumor suppressor (Rb)
      and cyclin-dependent kinase 4/6 (CDK4/6), increases phosphorylation at specific
      residues of Rb by CDK4/6 in vivo, and promotes tumorigenesis. The phosphorylation
      of Rb by CDK4/6 leads to the deregulation of the cell cycle during G1/S
      transition. Although how phosphorylation occurs on Rb has been studied
      extensively, the mechanism of site-specific phosphorylation of Rb remains unclear
      due to a lack of information on the structural arrangement of Rb and CDK4/6.
      Here, we have determined and refined to 2.3-A resolution the crystal structure of
      a gankyrin homolog, the non-ATPase subunit 6 (Nas6p) of the proteasome from
      yeast. The crystal structure reveals that Nas6p contains seven ankyrin repeats.
      The number of the repeats is different from that predicted from the primary
      structure. Nas6p also possesses an unusual curved structure with two acidic
      regions at the N- and C-terminal regions separated by one basic region,
      suggesting that it has at least two functional surfaces. The tertiary structure
      of Nas6p, together with the previous biochemical studies, indicates that the
      CDK4/6 and Rb binding surfaces of gankyrin are located at the N- and C-terminal
      regions, respectively, and face the same side of gankyrin. These observations
      suggest that gankyrin brings Rb and CDK4/6 together through gankyrin-Rb and
      gankyrin-CDK4/6 interactions and determines the relative positioning of the
      substrate (Rb) and the enzyme (CDK4/6). Our findings provide mechanistic insight
      into site-specific phosphorylation of Rb caused by CDK4/6.

PMID- 14583613
TI  - Hepatic erythropoietin gene regulation by GATA-4.
AB  - Erythropoietin production switches from fetal liver to adult kidney during
      development. GATA transcription factors 2 and 3 could be involved in modulating
      this switch, because they were shown to negatively regulate erythropoietin gene
      transcription through a promoter proximal GATA site. Herein, we analyzed the role
      of several GATA factors in the regulation of the erythropoietin gene in human
      liver and in hepatoma cells. Although GATA-3 expression in hepatocytes increases
      during human development, erythropoietin mRNA accumulation is unaltered in mutant
      mice lacking GATA-3. We found that GATA-2, -3, -4, and -6 are all expressed in
      human hepatocytes and that GATA-4 exhibits the most prominent Epo promoter
      binding activity in vitro and in vivo. Inhibition of GATA-4 expression by RNA
      interference leads to a dramatic reduction in Epo gene transcription in Hep3B
      cells. Moreover, GATA-4 expression is high and limited to hepatocytes in the
      fetal liver, whereas GATA-4 expression in the adult liver is low and restricted
      to epithelial cells surrounding the biliary ducts. Thus, GATA-4 is critical for
      transcription of the Epo gene in hepatocytes and may contribute to the switch in
      the site of Epo gene expression from the fetal liver to the adult kidney.

PMID- 14583614
TI  - Hepatocyte nuclear factor 4alpha is a central regulator of bile acid conjugation.
AB  - Hepatocyte nuclear factor 4alpha (HNF4alpha) has an important role in regulating
      the expression of liver-specific genes. Because bile acids are produced from
      cholesterol in liver and many enzymes involved in their biosynthesis are
      preferentially expressed in liver, the role of HNF4alpha in the regulation of
      bile acid production was examined. In mice, unconjugated bile acids are
      conjugated with taurine by the liver-specific enzymes, bile acid-CoA ligase and
      bile acid-CoA:amino acid N-acyltransferase (BAT). Mice lacking hepatic HNF4alpha
      expression exhibited markedly decreased expression of the very long chain acyl
      CoA synthase-related gene (VLACSR), a mouse candidate for bile acid-CoA ligase,
      and BAT. This was associated with markedly elevated levels of unconjugated and
      glycine-conjugated bile acids in gallbladder. HNF4alpha was found to bind
      directly to the mouse VLACSR and BAT gene promoters, and the promoter activities
      were dependent on HNF4alpha-binding sites and HNF4alpha expression. In
      conclusion, HNF4alpha plays a central role in bile acid conjugation by direct
      regulation of VLACSR and BAT in vivo.

PMID- 14583615
TI  - Molecular cloning and characterization of a protein farnesyltransferase from the
      enteric protozoan parasite Entamoeba histolytica.
AB  - Genes encoding alpha- and beta-subunits of a putative protein farnesyltransferase
      (FT) from the enteric protozoan parasite Entamoeba histolytica were obtained and
      their biochemical properties were characterized. Deduced amino acid sequences of
      the alpha- and beta-subunit of E. histolytica FT (EhFT) were 298- and 375
      residues long with a molecular mass of 35.6 and 42.6 kDa, and a pI of 5.43 and
      5.65, respectively. They showed 24% to 36% identity to and shared common
      signature domains and repeats with those from other organisms. Recombinant alpha-
      and beta-subunits, co-expressed in Escherichia coli, formed a heterodimer and
      showed activity to transfer farnesyl using farnesylpyrophosphate as a donor to
      human H-Ras possessing a C-terminal CVLS, but not a mutant H-Ras possessing CVLL.
      Among a number of small GTPases that belong to the Ras superfamily from this
      parasite, we identified EhRas4, which possesses CVVA at the C terminus, as a sole
      farnesyl acceptor for EhFT. This is in contrast to mammalian FT, which utilizes a
      variety of small GTPases that possess a C-terminal CaaX motif, where X is serine,
      methionine, glutamine, cysteine, or alanine. EhFT also showed remarkable
      resistance against a variety of known inhibitors of mammalian FT. These results
      suggest that remarkable biochemical differences in binding to substrates and
      inhibitors exist between amebic and mammalian FTs, which highlights this enzyme
      as a novel target for the development of new chemotherapeutics against amebiasis.

PMID- 14583616
TI  - The use of isotope effects to determine enzyme mechanisms.

PMID- 14583617
TI  - Tetrapandins, a new class of scorpion toxins that specifically inhibit store
      operated calcium entry in human embryonic kidney-293 cells.
AB  - Venoms from 14 snakes and four scorpions were screened for inhibitory activities
      toward store-operated Ca2+ entry (SOCE) in human embryonic kidney-293 cells. An
      inhibitory activity was found in venom from the African scorpion Pandinus
      imperator. The active agent of this venom was purified by gel filtration and
      reverse-phase high pressure liquid chromatography methods. Sequence information
      on the purified fraction, by automatic Edman degradation and mass spectrometry
      analysis, identified the activity as being contained in two tetrapeptides, which
      we have named tetrapandins. We demonstrate that synthesized tetrapandins have
      inhibitory activity for SOCE in human embryonic kidney-293 cells while having no
      effect on either thapsigargin- or carbachol-stimulated release of Ca2+ stores.
      These toxins should be extremely useful in future studies to determine downstream
      events regulated by SOCE as well as to determine whether multiple pathways exist
      for thapsigargin-stimulated Ca2+ entry.

PMID- 14583618
TI  - The low density lipoprotein receptor prevents secretion of dense apoB100
      containing lipoproteins from the liver.
AB  - The assembly and secretion of very low density lipoproteins (VLDL) require
      microsomal triglyceride transfer protein (MTP). Recent evidence also suggests a
      role for the low density lipoprotein (LDL) receptor in this process. However, the
      relative importance of MTP in the two steps of VLDL assembly and the specific
      role of the LDL receptor still remain unclear. To further investigate the role of
      MTP and the LDL receptor in VLDL assembly, we bred mice harboring "floxed" Mttp
      alleles (Mttpflox/flox) and a Cre transgene on a low-density lipoprotein receptor
      deficient background to generate mice with double deficiency in the liver (Ldlr-/
      MttpDelta/Delta). In contrast to the plasma of Ldlr+/+ MttpDelta/Delta mice, the
      plasma of Ldlr-/- MttpDelta/Delta mice contained apoB100. Accordingly, Ldlr-/-
      MttpDelta/Delta but not Ldlr+/+ MttpDelta/Delta hepatocytes secreted apoB100
      containing lipoprotein particles. The secreted lipoproteins were of LDL and HDL
      sizes but no VLDL-sized lipoproteins could be detected. These findings indicate
      that hepatic LDL receptors function as "gatekeepers" targeting dense apoB100
      containing lipoproteins for degradation. In addition, these results suggest that
      very low levels of MTP are insufficient to mediate the second step but sufficient
      for the first step of VLDL assembly.

PMID- 14583619
TI  - Substitution in position 3 of cyclosporin A abolishes the cyclophilin-mediated
      gain-of-function mechanism but not immunosuppression.
AB  - Binary complex formation between the immunosuppressive drug cyclosporin A (CsA)
      and cyclophilin 18 is the prerequisite for the ability of CsA to inhibit the
      protein phosphatase activity of calcineurin, a central mediator of antigen
      receptor signaling. We show here that several CsA derivatives substituted in
      position 3 can inhibit calcineurin without prior formation of a complex with
      cyclophilin 18. [Methylsarcosine(3)]CsA was shown to inhibit calcineurin, either
      in its free form with an IC(50) value of 10 microm, or in its complex form with
      cyclophilin 18 with an IC(50) of 500 nm. [Dimethylaminoethylthiosarcosine(3)]CsA
      ([Dat-Sar(3)]CsA) was found to inhibit calcineurin on its own, with an IC(50)
      value of 1.0 microm, but was not able to inhibit calcineurin after forming the
      [Dat-Sar(3)]CsA-cyclophilin 18 binary complex. Despite their different inhibitory
      properties, both CsA and [Dat-Sar(3)]CsA suppressed T cell proliferation and
      cytokine production mainly through blocking NFAT activation and interleukin-2
      gene expression. Furthermore, to demonstrate that [Dat-Sar(3)]CsA can inhibit
      calcineurin in a cyclophilin-independent manner in vivo, we tested its effect in
      a Saccharomyces cerevisiae strain (Delta12), in which all the 12 cyclophilins and
      FKBPs were deleted. [Dat-Sar(3)]CsA, but not CsA, bypassed the requirement for
      cellular cyclophilins and caused growth inhibition in the salt-stressed Delta12
      strain.

PMID- 14583620
TI  - DUB-1A, a novel deubiquitinating enzyme subfamily member, is polyubiquitinated
      and cytokine-inducible in B-lymphocytes.
AB  - Recently, we isolated the Dub-2A gene, which encodes a novel murine
      deubiquitinating enzyme subfamily member, from a bacterial artificial chromosome
      library clone by PCR amplification with degenerate PCR primers for the Dub-2 cDNA
      (Baek, K.-H., Mondoux, M. A., Jaster, R., Fire-Levin E., and D'Andrea, A. D.
      (2001) Blood 98, 636-642). In this study, we analyzed two more clones from the
      library to isolate genes encoding other deubiquitinating enzymes. Dub-1A, which
      encodes the shortest member of the DUB subfamily of deubiquitinating enzymes so
      far, has been identified in both clones and characterized. Sequence analysis
      showed that Dub-1A encodes a 468-amino acid protein that has a molecular mass of
      approximately 51 kDa and that contains a putative catalytic domain (Cys, His, and
      Asp) conserved among DUB proteins. The amino acid sequence of DUB-1A is 84.5,
      84.7, and 85.3% identical to those of DUB-1, DUB-2, and DUB-2A, respectively.
      Reverse transcription-PCR revealed that Dub-1A is expressed not only in B
      lymphocytes in response to interleukin-3 stimulation, but also in T-lymphocytes,
      brain, heart, liver, lung, kidney, ovary, and spleen. This suggests that Dub-1A
      may play essential roles in each of these organs. In vivo and in vitro
      deubiquitinating enzyme assays showed that DUB-1A has functional deubiquitinating
      activity and that the 5'-flanking sequence of Dub-1A has a functional enhancer
      domain as shown in Dub-1 and Dub-2A. Interestingly, immunoblot analysis revealed
      that DUB-1A is polyubiquitinated, indicating that it is degraded through
      proteasome-mediated degradation. In the absence of JAK2, Dub-1A was expressed at
      a lower level. This suggests that DUB-1A functions downstream of JAK2 kinase in
      the interleukin-3 signaling pathway.

PMID- 14583621
TI  - Molecular cloning and functional expression of zfCx52.6: a novel connexin with
      hemichannel-forming properties expressed in horizontal cells of the zebrafish
      retina.
AB  - Gap junction-mediated electrical coupling contributes to synchronous oscillatory
      activities of neurons, and considerable progress has been made in defining the
      molecular composition of gap junction channels. In particular, cloning and
      functional expression of gap junction proteins (connexins (Cx)) from zebrafish
      retina have shown that this part of the brain possesses a high degree of connexin
      diversity that may account for differential functional properties of electrical
      synapses. Here, we report the cloning and functional characterization of a new
      connexin, designated zebrafish Cx52.6 (zfCx52.6). This connexin shows little
      similarity to known connexins from fish and higher vertebrates. By combining in
      situ hybridization with Laser Capture Microdissection and RT-PCR, we found that
      this novel fish connexin is expressed in horizontal cells in the inner nuclear
      layer of the retina. Functional expression of zfCx52.6 in neuroblastoma cells and
      Xenopus oocytes led to functional gap junctional channels and, in single oocytes,
      induced large non-junctional membrane currents indicative of the formation of
      hemichannels, which were inhibited in reversible fashion by raising extracellular
      Ca(2+) concentrations.

PMID- 14583622
TI  - An endogenous HIV envelope-derived peptide without the terminal NH3+ group anchor
      is physiologically presented by major histocompatibility complex class I
      molecules.
AB  - Cytotoxic T lymphocytes (CTL) recognize viral peptidic antigens presented by
      major histocompatibility complex (MHC) class I molecules on the surface of
      infected cells. The CTL response is critical in clearance and prevention of HIV
      infection. Yet, there are no descriptions of physiological peptides derived from
      the viral envelope protein. In the few reports on endogenous MHC class I viral
      peptidic ligands from HIV internal proteins, definitive positive identification
      by mass spectrometry is lacking. The HIV-1 envelope glycoprotein gp160 induces a
      strong specific CTL response restricted by several human and murine MHC class I
      molecules, including H-2Dd. Previous analyses showed that this response can be
      optimally mimicked with the synthetic decameric peptide 318RGPGRAFVTI327. We aim
      to identify the endogenous natural peptides mediating the response to this
      epitope. Our data indicate the presence of, at least, two peptidic species of
      different length and sharing the same antigenic core, which are associated with
      the Dd presenting molecule in infected cells. One species is at least, probably,
      the optimal decapeptide. The second species, identified by mass spectrometry for
      the first time in HIV, is, unexpectedly, a nonamer, which lacks the correctly
      positioned N-terminal group to bind to Dd. And yet, it is present in similar
      amounts and, notably, is equally antigenic. Thus, the physiological set of HIV
      derived MHC class I ligands is richer and different than expected from studies
      with synthetic peptides. This may help raise the plasticity and thus the
      effectiveness of the immune response against the viral infection. These data have
      implications for HIV vaccine development.

PMID- 14583624
TI  - Importance of the amino terminus in secretin family G protein-coupled receptors.
      Intrinsic photoaffinity labeling establishes initial docking constraints for the
      calcitonin receptor.
AB  - The calcitonin receptor is a member of the class B family of G protein-coupled
      receptors, closely related to secretin and parathyroid hormone receptors.
      Although mechanisms of ligand binding have been directly explored for those
      receptors, current knowledge of the molecular basis of calcitonin binding to its
      receptor is based only on receptor mutagenesis. In this work we have utilized the
      more direct approach of photoaffinity labeling to explore spatial approximations
      between distinct residues within calcitonin and its receptor. For this we have
      developed two human calcitonin analogues incorporating a photolabile p-benzoyl-l
      phenylalanine residue in the mid-region and carboxyl-terminal half of the peptide
      in positions 16 and 26, respectively. Both probes specifically bound to the human
      calcitonin receptor with high affinity and were potent stimulants of cAMP
      accumulation in calcitonin receptor-bearing human embryonic kidney 293 cells.
      They covalently labeled the calcitonin receptor in a saturable and specific
      manner. Further purification, deglycosylation, specific chemical and enzymatic
      cleavage, and sequencing of labeled wild type and mutant calcitonin receptors
      identified the sites of labeling for the position 16 and 26 probes as receptor
      residues Phe137 and Thr30, respectively. Both were within the extracellular amino
      terminus of the calcitonin receptor, with the former adjacent to the first
      transmembrane segment and the latter within the distal amino-terminal tail of the
      receptor. These data are consistent with affinity labeling of other members of
      the class B G protein-coupled receptors using analogous probes and may suggest a
      common ligand binding mechanism for this family.

PMID- 14583623
TI  - Human fibrillarin forms a sub-complex with splicing factor 2-associated p32,
      protein arginine methyltransferases, and tubulins alpha 3 and beta 1 that is
      independent of its association with preribosomal ribonucleoprotein complexes.
AB  - Fibrillarin (FIB, Nop1p in yeast) is an RNA methyltransferase found not only in
      the fibrillar region of the nucleolus but also in Cajal bodies. FIB is essential
      for efficient processing of preribosomal RNA during ribosome biogenesis, although
      its precise function in this process and its role in Cajal bodies remain
      uncertain. Here, we demonstrate that the human FIB N-terminal glycine- and
      arginine-rich domain (residues 1-77) and its spacer region 1 (78-132) interact
      with splicing factor 2-associated p32 (SF2A-p32) and that the FIB
      methyltransferase-like domain (133-321) interacts with protein-arginine
      methyltransferase 5 (PRMT5, Janus kinase-binding protein 1). We also show that
      these proteins associate with several additional proteins, including PRMT1,
      tubulin alpha 3, and tubulin beta 1 to form a sub-complex that is principally
      independent of the association of FIB with preribosomal ribonucleoprotein
      complexes that co-immunoprecipitate with the sub-complex in human cells
      expressing FLAG-tagged FIB. Based on the physical association of FIB with SF2A
      p32 and PRMTs, as well as the other reported results, we propose that FIB may
      coordinate both RNA and protein methylation during the processes of ribosome
      biogenesis in the nucleolus and RNA editing such as small nuclear (nucleolar)
      ribonucleoprotein biogenesis in Cajal bodies.

PMID- 14583625
TI  - An engineered hyaluronan synthase: characterization for recombinant human
      hyaluronan synthase 2 Escherichia coli.
AB  - The Class I hyaluronan synthase (HAS) is a unique glycosyltransferase
      synthesizing hyaluronan (HA), a polysaccharide composed of GlcUA and GlcNAc, by
      using one catalytic domain that elongates two different monosaccharides. As for
      the synthetic mechanism, there are two alternative manners for the sugar
      elongation process. Some bacterial HASs add new sugars to the non-reducing end of
      the acceptor to grow polymers. On the other hand, some vertebrate enzymes seem to
      transfer sugars to the reducing end. Expression of vertebrate HASs as active and
      soluble proteins will accelerate further precise insight into mechanisms of sugar
      elongation reactions by natural HASs. Since large scale production of HA polymers
      and oligomers would become powerful tools both for basic studies and new
      biotechnology to create functional carbohydrates in medicinal purposes, advent of
      an efficient method for the expression of HASs in Escherichia coli is strongly
      expected. Here we communicate the first success of the production of recombinant
      human HAS2 proteins composed of only the catalytic region in E. coli as the
      active form. It was demonstrated that an engineered HAS2 expressed in E. coli
      exhibited significant activity to synthesize a mixture of HAS oligomers from 8
      mer (HA8) to 16-mer (HA16). Engineered HAS2 prepared herein elongated sugars from
      exogenous tetrasaccharide to form polymers with a direction to the non-reducing
      end. According to the present results, large scale production of engineered
      recombinant HASs is to be performed using E. coli that will provide practical and
      economic advantages in manufacturing enzymes for use in the synthesis of various
      oligomeric HA molecules and their industrial applications.

PMID- 14583626
TI  - Cerebroside sulfotransferase deficiency ameliorates L-selectin-dependent monocyte
      infiltration in the kidney after ureteral obstruction.
AB  - Mononuclear cells infiltrating the interstitium are involved in renal
      tubulointerstitial injury. The unilateral ureteral obstruction (UUO) is an
      established experimental model of renal interstitial inflammation. In our
      previous study, we postulated that L-selectin on monocytes is involved in their
      infiltration into the interstitium by UUO and that a sulfated glycolipid,
      sulfatide, is the physiological L-selectin ligand in the kidney. Here we tested
      the above hypothesis using sulfatide- and L-selectin-deficient mice. Sulfatide
      deficient mice were generated by gene targeting of the cerebroside
      sulfotransferase (Cst) gene. Although the L-selectin-IgG chimera protein
      specifically bound to sulfatide fraction in acidic lipids from wild-type kidney,
      it did not show such binding in fractions of Cst(-/-) mice kidney, indicating
      that sulfatide is the major L-selectin-binding glycolipid in the kidney. The
      distribution of L-selectin ligand in wild-type mice changed after UUO; sulfatide
      was relocated from the distal tubules to the peritubular capillaries where
      monocytes infiltrate, suggesting that sulfatide relocated to the endothelium
      after UUO interacted with L-selectin on monocytes. In contrast, L-selectin ligand
      was not detected in Cst(-/-) mice irrespective of UUO treatment. Compared with
      wild-type mice, Cst(-/-) mice showed a considerable reduction in the number of
      monocytes/macrophages that infiltrated the interstitium after UUO. The number of
      monocytes/macrophages was also reduced to a similar extent in L-selectin(-/-)
      mice. Our results suggest that sulfatide is a major L-selectin-binding molecule
      in the kidney and that the interaction between L-selectin and sulfatide plays a
      critical role in monocyte infiltration into the kidney interstitium.

PMID- 14583627
TI  - Evidence for antagonistic regulation of cell growth by the calcineurin and high
      osmolarity glycerol pathways in Saccharomyces cerevisiae.
AB  - Because Ca(2+) signaling of budding yeast, through the activation of calcineurin
      and the Mpk1/Slt2 mitogen-activated protein kinase cascade, performs redundant
      function(s) in the events essential for growth, the simultaneous deletion of both
      these pathways (Delta cnb1 Delta mpk1) leads to lethality. A PTC4 cDNA that
      encodes a protein phosphatase belonging to the PP2C family was obtained as a high
      dosage suppressor of the lethality of Delta cnb1 Delta mpk1 strain.
      Overexpression of PTC4 led to a decrease in the high osmolarity-induced Hog1
      phosphorylation, and HOG1 deletion remarkably suppressed the synthetic lethality,
      indicating an antagonistic role of the high osmolarity glycerol (HOG) pathway and
      the Ca(2+) signaling pathway in growth regulation. The calcineurin-Crz1 pathway
      was required for the down-regulation of the HOG pathway. Analysis of the time
      course of actin polarization, bud formation, and the onset of mitosis in
      synchronous cell cultures demonstrated that calcineurin negatively regulates
      actin polarization at the bud site, whereas the HOG pathway positively regulates
      bud formation at a later step after actin has polarized.

PMID- 14583628
TI  - Protein sorting in the late Golgi of Saccharomyces cerevisiae does not require
      mannosylated sphingolipids.
AB  - Glycosphingolipids are widely viewed as integral components of the Golgi-based
      machinery by which membrane proteins are targeted to compartments of the
      endosomal/lysosomal system and to the surface domains of polarized cells. The
      yeast Saccharomyces cerevisiae creates glycosphingolipids by transferring mannose
      to the head group of inositol phosphorylceramide (IPC), yielding mannosyl-IPC
      (MIPC). Addition of an extra phosphoinositol group onto MIPC generates mannosyldi
      IPC (M(IP)2C), the final and most abundant sphingolipid in yeast. Mannosylation
      of IPC is partially dependent on CSG1, a gene encoding a putative
      sphingolipidmannosyltransferase. Here we show that open reading frame YBR161w,
      renamed CSH1, is functionally homologous to CSG1 and that deletion of both genes
      abolishes MIPC and M(IP)2C synthesis without affecting protein mannosylation.
      Csg1p and Csh1p are closely related polytopic membrane proteins that co-localize
      with IPC synthase in the medial-Golgi. Loss of Csg1p and Csh1p has no effect on
      clathrin- or AP-3 adaptor-mediated protein transport from the Golgi to the
      vacuole. Moreover, segregation of the periplasmic enzyme invertase, the plasma
      membrane ATPase Pma1p and the glycosylphosphatidylinositol-anchored protein Gas1p
      into distinct classes of secretory vesicles occurs independently of Csg1p and
      Csh1p. Our results indicate that protein sorting in the late Golgi of yeast does
      not require production of mannosylated sphingolipids.

PMID- 14583629
TI  - Diacylglycerols containing Omega 3 and Omega 6 fatty acids bind to RasGRP and
      modulate MAP kinase activation.
AB  - We elucidated the effects of different diacylglycerols (DAGs), i.e. 1-stearoyl-2
      arachidonoyl-sn-glycerol (SAG), 1-stearoyl-2-docosahexaenoyl-sn-glycerol (SDG),
      and 1-stearoyl-2-eicosapentaenoyl-sn-glycerol (SEG), on [3H]PDBu binding to
      RasGRP. The competition studies with these DAGs on [3H]PDBu binding to RasGRP
      revealed different Ki values for these DAG molecular species. Furthermore, we
      transfected human Jurkat T cells by a plasmid containing RasGRP and assessed the
      implication of endogenous DAGs on activation of MAP kinases ERK1/ERK2, induced by
      phorbol-12-myristate-13-acetate (PMA). In control cells, GF109203X, a protein
      kinase C inhibitor, inhibited ERK1/ERK2 activation. However, this agent curtailed
      but failed to completely diminish ERK1/ERK2 phosphorylation in RasGRP
      overexpressing cells, though calphostin C, a DAG binding inhibitor, suppressed
      the phosphorylation of MAP kinases in these cells. In cells incubated with
      arachidonic acid (AA), docosahexaenoic acid (DHA), and eicosapentaenoic acid
      (EPA), PMA induced the production of endogenous DAGs containing these fatty
      acids, respectively: DAG-AA, DAG-DHA, and DAG-EPA. The inhibition of production
      of DAG-AA and DAG-DHA significantly inhibited MAP kinase activation in RasGRP
      overexpressing, but not in control, cells. Our study demonstrates that three DAG
      molecular species bind to RasGRP, but only DAG-AA and DAG-DHA participate in the
      modulation of RasGRP-mediated activation of MAP kinases in Jurkat T cells.

PMID- 14583630
TI  - Caspase-7 gene disruption reveals an involvement of the enzyme during the early
      stages of apoptosis.
AB  - Caspases play a key role during apoptotic execution. In an attempt to elucidate
      the specific role of caspase-7 we generated a chicken DT40 cell line in which
      both alleles of the gene were disrupted. Viability assays showed that caspase-7-/
      clones are more resistant to the common apoptosis-inducing drugs etoposide and
      staurosporine. Caspase-7-/- cells show a delay in phosphatidylserine
      externalization and DNA fragmentation as well as cleavage of the caspase
      substrates poly(ADP-ribose) polymerase 1 and lamins B1 and B2. Caspase affinity
      labeling and activity assays indicated that deficient cells exhibit a delay in
      caspase activation compared with wild type DT40 cells, providing an explanation
      for the differences in apoptotic execution between caspase-7 null and wild type
      DT40 cells. These results strongly suggest that caspase-7 is involved earlier
      than other effector caspases in the apoptotic execution process in DT40 B
      lymphocytes.

PMID- 14583631
TI  - Qbeta-phage resistance by deletion of the coiled-coil motif in elongation factor
      Ts.
AB  - Elongation factor Ts (EF-Ts) is the guanine-nucleotide exchange factor of
      elongation factor Tu (EF-Tu), which promotes the binding of aminoacyl-tRNA to the
      mRNA-programmed ribosome in prokaryotes. The EF-Tu.EF-Ts complex, one of the EF
      Tu complexes during protein synthesis, is also a component of RNA-dependent RNA
      polymerases like the polymerase from coliphage Qbeta. The present study shows
      that the Escherichia coli mutant GRd.tsf lacking the coiled-coil motif of EF-Ts
      is completely resistant to phage Qbeta and that Qbeta-polymerase complex
      formation is not observed. GRd.tsf is the first E. coli mutant ever described
      that is unable to form a Qbeta-polymerase complex while still maintaining an
      almost normal growth behavior. The phage resistance correlates with an observed
      instability of the mutant EF-Tu.EF-Ts complex in the presence of guanine
      nucleotides. Thus, the mutant EF-Tu.EF-Ts is the first EF-Tu.EF-Ts complex ever
      described that is completely inactive in the Qbeta-polymerase complex despite its
      almost full activity in protein synthesis. We propose that the role of EF-Ts in
      the Qbeta-polymerase complex is to control and trap EF-Tu in a stable
      conformation with affinity for RNA templates while unable to bind aminoacyl-tRNA.

PMID- 14583632
TI  - The mechanism of oxidative stress stabilization of the thromboxane receptor in
      COS-7 cells.
AB  - The 8-iso-prostaglandin F(2alpha), a prostanoid produced in vivo by
      cyclooxygenase-independent free-radical-catalyzed lipid peroxidation, acts as a
      partial agonist on the thromboxane receptor (TXA(2)R) and is a potent
      vasoconstrictor in the oxidatively stressed isolated perfused rat heart. We
      hypothesized that the response in the isolated heart may be due to augmentation
      of TXA(2)R density, which may be initiated by the presence of oxidative radicals.
      Previous studies have shown that TXA(2)R density is increased during
      atherosclerosis on both the medial and intimal smooth muscle layers in human
      coronary arteries. Here we describe the effect of oxidative stress on TXA(2)R.
      The thromboxane A(2) receptor beta isoform (TXA(2)Rbeta) was transiently
      expressed in COS-7 cells. Immunofluorescence suggested that the presence of
      H(2)O(2) increased translocation of TXA(2)Rbeta from the endoplasmic reticulum
      (ER) to the Golgi complex. H(2)O(2) treatment also increased binding of a TXA(2)R
      antagonist ([(3)H]SQ29548) to membranes. Degradation kinetics of TXA(2)Rbeta
      following cycloheximide treatment, a protein synthesis inhibitor, suggested not
      only that TXA(2)Rbeta is a short-lived protein predominantly localized to the ER
      but also that TXA(2)Rbeta degradation is modulated in the presence of H(2)O(2).
      Our results indicate that oxidative stress induces maturation and stabilization
      of the TXA(2)Rbeta protein probably by intracellular translocation. Importantly,
      these observations also suggest that TXA(2)Rbeta levels are modulated by ER
      associated degradation and controlled by the efficiency of transport to post-ER
      compartments. Stabilization of the TXA(2)Rbeta by translocation from a
      degradative compartment, i.e. the ER, can account for the augmentation of
      receptor density observed in vivo.

PMID- 14583634
TI  - Mouse chromosome 17A3.3 contains 13 genes that encode functional tryptic-like
      serine proteases with distinct tissue and cell expression patterns.
AB  - Probing of the mouse EST data base at GenBank trade mark with known tryptase
      cDNAs resulted in the identification of undiscovered serine protease transcripts
      whose genes reside at a 1.5-Mb complex on mouse chromosome 17A3.3. Mouse tryptase
      5 (mT5), tryptase-6 (mT6), and mast cell protease-11 (mMCP-11) are new members of
      this serine protease superfamily whose amino acid sequences are 36-54% identical
      to each other and to their other 10 family members. The 13 functional mouse
      proteases can be subdivided into two subgroups based on conserved features in
      their propeptides. Of the three new serine proteases, mT6 is most widely
      expressed in tissues. mT5 is preferentially expressed in smooth muscle, whereas
      mMCP-11 is preferentially expressed in the spleen and bone marrow. In contrast to
      mT5 and mT6, mMCP-11 is also expressed in mast cells. Although mT6 and mMCP-11
      are constitutively secreted when expressed in mammalian and insect cells, mT5
      remains membrane-associated. The fact that recombinant mT5, mT6, and mMCP-11
      possess non-identical expression patterns and substrate specificities suggests
      that each protease has a unique function in vivo. Of the 13 functional mouse
      tryptase genes identified at the complex, 12 have orthologs that reside in the
      syntenic region of human chromosome 16p13.3. The establishment of these ortholog
      pairs helps clarify the evolutionary relationship of the serine protease locus in
      the two species. This information provides a useful framework for the functional
      analysis of each protease using gene targeting and other molecular approaches.

PMID- 14583633
TI  - The antitumor properties of the alpha3(IV)-(185-203) peptide from the NC1 domain
      of type IV collagen (tumstatin) are conformation-dependent.
AB  - Tumor progression may be controlled by various fragments derived from
      noncollagenous 1 (NC1) C-terminal domains of type IV collagen. We demonstrated
      previously that a peptide sequence from the NC1 domain of the alpha3(IV) collagen
      chain inhibits the in vitro expression of matrix metalloproteinases in human
      melanoma cells through RGD-independent binding to alpha(v)beta(3) integrin. In
      the present paper, we demonstrate that in a mouse melanoma model, the NC1
      alpha3(IV)-(185-203) peptide inhibits in vivo tumor growth in a conformation
      dependent manner. The decrease of tumor growth is the result of an inhibition of
      cell proliferation and a decrease of cell invasive properties by down-regulation
      of proteolytic cascades, mainly matrix metalloproteinases and the plasminogen
      activation system. A shorter peptide comprising the seven N-terminal residues 185
      191 (CNYYSNS) shares the same inhibitory profile. The three-dimensional
      structures of the CNYYSNS and NC1 alpha3(IV)-(185-203) peptides show a beta-turn
      at the YSNS (188-191) sequence level, which is crucial for biological activity.
      As well, the homologous MNYYSNS heptapeptide keeps the beta-turn and the
      inhibitory activity. In contrast, the DNYYSNS heptapeptide, which does not form
      the beta-turn at the YSNS level, is devoid of inhibitory activity. Structural
      studies indicate a strong structure-function relationship of the peptides and
      point to the YSNS turn as necessary for biological activity. These peptides could
      act as potent and specific antitumor antagonists of alpha(v)beta(3) integrin in
      melanoma progression.

PMID- 14583635
TI  - In vitro inhibitory effects of tea polyphenols on the proliferation of Chlamydia
      trachomatis and Chlamydia pneumoniae.
AB  - In vitro inhibitory effects of tea polyphenols on Chlamydia trachomatis and C.
      pneumoniae were investigated. A product of tea polyphenols, Polyphenon 70S was
      used. Chlamydial strains used were C. trachomatis D/UW-3/Cx and L(2)/434/Bu, and
      C. pneumoniae AR-39 and AC-43 strains. HeLa229 cells and HL cells were used for
      cultivation of C. trachomatis and C. pneumoniae, respectively. In the post
      inoculation method, no inclusions of C. trachomatis were observed at 0.5 mg/ml of
      Polyphenon 70S. However, the toxicity of Polyphenon 70S was noted in HeLa229
      cells and HL cells at a concentration of 0.25 mg/ml. In the pre-inoculation
      method, no toxic effects of Polyphenon 70S on the cells were noted. Complete
      inhibition of C. trachomatis D and L(2) was noted at concentrations of 1.6 and
      0.4 mg/ml, respectively. With C. pneumoniae strains, the end points were 0.8 and
      1.6 mg/ml for AR-39 and AC-43, respectively. Our findings encouraged the
      application of tea polyphenols for topical usage.

PMID- 14583636
TI  - Chlamydophila pneumoniae infection among young children with respiratory diseases
      in Thailand.
AB  - A total of 136 children aged 5 years and under with respiratory tract diseases
      were examined for Chlamydophila pneumoniae infection. By means of the micro
      immunofluorescence test, an acute infection was suggested in 37 (27.2%) of them.
      Infection was found in 23 (43.4%) of 53 children with bronchitis, seven (70.0%)
      of 10 with pharyngitis, and two (22.2%) of nine with pneumonia. C. pneumoniae DNA
      was detected in seven of 55 children by means of nasopharyngeal swabs, and
      serological evidence was present in all of seven. Five of them were suggested the
      acute infection and four of the five showed IgG titers increasing four times and
      over. By age distribution, five of the seven DNA-positive children were 1 year
      old, and the remaining two were 2 and 4 years old, respectively. The clinical
      findings of the seven DNA-positive children were characterized as indicative of
      bronchitis (n = 4), pharyngitis (n = 2), and pneumonia (n = 1). In Thailand, C.
      pneumoniae infection occurs frequently among children aged 5 years and under, and
      may cause pharyngitis, bronchitis, and sometimes pneumonia. However, it is
      suggested that C. pneumoniae infection is not a major cause of severe pneumonia
      among children in that age group.

PMID- 14583637
TI  - Multiplex polymerase chain reaction assay for selective detection of Salmonella
      enterica serovar typhimurium.
AB  - A multiplex polymerase chain reaction (PCR) assay was developed for the
      identification of Salmonella enterica serovar Typhimurium. Three sets of primers
      were designed for detecting O4, H:i, and H:1,2 antigen genes from the antigen
      specific genes rfbJ, fliC, and fljB, respectively. These were evaluated in a
      multiplex PCR assay by using DNAs from S. enterica serovar Typhimurium, 15 other
      Salmonella serovars, and 8 non-Salmonella enteric pathogens. Multiplex PCR proved
      to be capable of identifying S. enterica serovar Typhimurium specifically and
      differentiating it from other Salmonella serovars in addition to non-Salmonella
      enteric pathogens. Thus, this multiplex PCR assay can be practically applied to
      the identification of S. enterica serovar Typhimurium.

PMID- 14583638
TI  - Combination effect of ciprofloxacin and gentamicin against clinical isolates of
      Salmonella enterica serovar typhi with reduced susceptibility to ciprofloxacin.
AB  - The present study evaluated the in vitro efficacy of ciprofloxacin (CPFX) in
      combination with gentamicin (GM) using agar dilution checkerboard method against
      six blood culture isolates of Salmonella enterica serovar Typhi with CPFX minimum
      inhibitory concentration (MIC) values of 0.75 - 1.25 microg/ml and GM MIC values
      of 0.75 - 2 microg/ml. When used in combination, the fractional inhibitory
      concentration (FIC) values of CPFX and GM for the isolates ranged from 0.008 -
      0.032 microg/ml and 0.1 - 0.2 microg/ml, respectively. The range of the FIC index
      from 0.121 - 0.216 indicated the synergistic effect between CPFX and GM for all
      the isolates. The time-kill method, which showed a 2.64 log(10) decrease in
      CFU/ml between the combination and its more active compound, also established
      synergism between CPFX and GM against one isolate employed in the method. These
      results may be helpful in making clinical decisions in the treatment of enteric
      fever due to the infection of multidrug resistant S. enterica serovar Typhi.

PMID- 14583639
TI  - Safe and easy monitoring of anti-rabies antibody in dogs using his-tagged
      recombinant N-protein.
AB  - The virus neutralization (VN) test is a reliable indicator of adequate
      vaccination in animals. However, the VN test is tedious and complicated to
      perform. Enzyme-linked immunosorbent assay (ELISA), though rapid and simple
      compared to the VN test, is complicated and hazardous during preparation of the
      viral antigen. In an effort to overcome the disadvantage of ELISA, the
      recombinant His-tagged nucleoprotein (His-rNP) expressed in Escherichia coli was
      used as a safe antigen for ELISA (i.e., live virus was not used). Anti-rabies
      antibody levels were determined by fluorescent ELISA (FELISA) using His-rNP as an
      antigen. The presence of anti-rabies VN antibody was determined by the rapid
      fluorescent focus inhibition test (RFFIT). The VN titers by RFFIT were found to
      correlate well with the FITC-signal determined by the FELISA (r = 0.616). The
      sensitivity and specificity of the FELISA were 91.7 and 100%, respectively. This
      study showed that the His-rNP could be useful as an antigen of ELISA to test for
      anti-rabies antibody in vaccinated dogs. Several studies in Japan have
      investigated the antibody level in the sera of vaccinated dogs. A safe and
      convenient test using His-rNP would contribute to our understanding of the status
      of herd immunity among not only domestic dogs but also stray dogs in Japan.

PMID- 14583640
TI  - Evaluation of a rapid serological chromatographic immunoassay for the diagnosis
      of pulmonary tuberculosis in Accra, Ghana.
AB  - Advances in serologic assays for tuberculosis (TB) have made serology an
      attractive surveillance tool. The sensitivity, specificity, and predictive value
      of these new assays have been well established. We employed an
      immunochromatographic serodiagnostic test for detecting antibodies
      (immunoglobulin [Ig] G, IgA, and IgM) specific for mycobacteria-specific antigen
      60 (A60) in the serum of suspected TB patients (n=310) attending the Chest Clinic
      of the Korle-Bu Teaching Hospital, Accra, Ghana. Compared to the gold standard,
      sputum culture, the performance indexes of the test kit indicated a sensitivity
      of 80% and a specificity of 98.2%, respectively. The positive predictive value
      and the likelihood ratios for positive and negative results were 96.6, 44.4, and
      0.2%, respectively, when compared to sputum culture. Our results suggest that the
      serodiagnostic test kit may be a valuable tool for the diagnosis of TB, and can
      provide simple and satisfactory results, particularly in cases in which TB is
      clinically difficult to diagnose by the usual clinical and laboratory tests.

PMID- 14583641
TI  - Prevalence of antibodies to syphilis among blood donors in Accra, Ghana.
AB  - Several infectious diseases have been found to be associated with transfusion of
      blood and blood components. Reports from studies conducted in many African
      countries indicate a high incidence of blood-borne pathogens such as syphilis
      infections among healthy blood donors. The prevalence of syphilis antibodies in
      blood donors in Ghana is not known. This study was therefore conducted in order
      to determine the prevalence of antibodies to syphilis among blood donors seen
      between the months of January and March 2003 at the National Blood Transfusion
      Service, Accra area (Blood Bank) at the Korle-Bu Teaching Hospital, Accra, Ghana.
      The presence of antibodies specific for syphilis was tested using Venereal
      Disease Research Laboratory and particle agglutination test kit. A sero
      prevalence rate of 7.5% was found. Our sample of blood donors was largely
      comprised of male subjects (500 out of 536 donors, and only 1 out of the 36
      screened female donors was positive), making sex comparisons statistically
      undesirable. In both sexes, the age distribution of subjects positive for
      syphilis antibodies was from 19 - 54 (median age, 32) years. In conclusion, our
      results indicate that syphilis is prevalent among healthy blood donors in Ghana,
      and that there is a need to introduce the screening of donated blood for syphilis
      in Ghana.

PMID- 14583642
TI  - Epidemiological investigation on Clonorchis sinensis in human population in an
      area of South China.
AB  - To detect the prevalence of Clonorchis sinensis, one of the important helminthes
      in the human population of the Guangxi Region where Schistosoma japonicum was
      endemic but eliminated in the late 1980s, the Kato-Katz thick smear technique was
      used for examining fecal samples from selected townships in Hengxian County.
      Among 1,552 people examined, 491 (31.6%) were found infected with C. sinensis. By
      counting eggs per gram feces (EPG), it was found that the light, moderate, and
      heavy intensities of infection occupied 55.4, 33.0, and 11.6%, respectively, with
      an average EPG of 4,845 in the infected subjects. The survey revealed that the
      prevalence in the age groups of 0 - 9 and 10 -19 years old was less than 10% but
      was 45 - 50% in the groups between 30 - 39 and 60 - 69 years old. A much higher
      prevalence was demonstrated in the male population (41.9%) than in the females
      (20.5%), and heavier intensity of infection was also found in the males than in
      the females. These results indicated that the prevalence of this liver fluke is
      increasing in the past decade in that region, and there is an urgent need to
      further assess the epidemiological factors in reference to the area's changing
      socioeconomic conditions and human behavior, contamination of the environment and
      fish ponds, inadequate farming/fishery practices, and the infection of domestic
      animals.

PMID- 14583643
TI  - Evaluation of simian immunodeficiency virus-specific immune responses induced by
      a defective proviral DNA vaccine in macaques.

PMID- 14583644
TI  - Arithmetic estimation of the HIV-infected in Japan.

PMID- 14583645
TI  - Vaccination coverage of poliomyelitis among less than 5-year-old children in the
      markets of Niger.

PMID- 14583646
TI  - An unusual outbreak of infusion-related bacteremia in a gastrointestinal disease
      ward.

PMID- 14583647
TI  - P genotypic identification of human group A rotaviruses.

PMID- 14583648
TI  - A red fox, Vulpes vulpes shrencki, infected with Echinococcus multilocularis was
      introduced from Hokkaido Island, where E. multilocularis is endemic, to Aomori,
      northern part of the mainland Japan.

PMID- 14583649
TI  - Molecular epidemiology of type 2 vaccine-associated paralytic poliomyelitis in
      china.

PMID- 14583650
TI  - Collaborative study: Standardization of Japanese reference diphtheria and tetanus
      toxoids, (adsorbed, lot 2), for potency determination of diphtheria-tetanus-
      acellular pertussis combined vaccine.

PMID- 14583651
TI  - Transgenesis and the study of expression, cellular targeting and function of
      oxytocin, vasopressin and their receptors.
AB  - The neuropeptides oxytocin and vasopressin and the neurons in the hypothalamus
      that synthesize them have been a rich source for the exploration and
      understanding of both the brain and the endocrine system. Because of their large
      size and compact nuclear organization the magnocellular neurons of the
      hypothalamoneurohypophysial system have traditionally attracted scientists using
      state-of-the-art techniques, including the subject of this review, transgenesis.
      We discuss the role of transgenics in deciphering gene elements necessary for the
      appropriate expression of oxytocin and vasopressin and to deliver exogenous
      genes, such as green fluorescent protein, selectively to secretory granules in
      the neurons in the hypothalamoneurohypophysial system. Finally, we review the
      studies of mice whose genes for oxytocin and, most recently, for the oxytocin and
      vasopressin receptors have been knocked out through homologous recombination.

PMID- 14583652
TI  - Critical role for estrogen receptor alpha in negative feedback regulation of
      gonadotropin-releasing hormone mRNA expression in the female mouse.
AB  - Estrogen exerts an important regulatory influence upon the functioning of the
      gonadotropin-releasing hormone (GnRH) neurons. Whether this is mediated by
      estrogen receptor alpha (ERalpha) or ERbeta or both ERs is presently unclear.
      Using female mice with targeted disruptions of ERalpha and ERbeta (alphaERKO and
      betaERKO, respectively) we have investigated the in vivo role of the two ERs in
      the negative feedback influence of estrogen upon GnRH mRNA expression. Compared
      with intact wild-type mice, plasma luteinizing hormone (LH) levels were
      substantially (p < 0.01) higher in intact alphaERKO females and increased
      modestly (p < 0.05) in intact betaERKO mice. Three weeks after ovariectomy, LH
      concentrations were elevated significantly in wild-type (p < 0.01) and betaERKO
      (p < 0.05) mice but not changed in alphaERKO females. Quantitative analysis of
      GnRH mRNA expression using in situ hybridization revealed that cellular GnRH mRNA
      content was greater (p < 0.05) in intact alphaERKO mice compared with intact wild
      type and betaERKO mice. Following ovariectomy, GnRH mRNA expression was elevated
      in wild-type (p = 0.06) and betaERKO (p < 0.05) females but not alphaERKO mice.
      These data demonstrate that both ERalpha and ERbeta are involved in inhibiting LH
      levels at times of estrogen-negative feedback in vivo. However, only ERalpha
      appears to be critical for the estrogen-negative feedback suppression of GnRH
      mRNA expression in the female mouse.

PMID- 14583653
TI  - Can growth hormone (GH) accelerate aging? Evidence from GH-transgenic mice.
AB  - Overexpression of heterologous growth hormone (GH) in transgenic mice results in
      numerous phenotypic effects, including a drastically shortened life span. Early
      onset of pathological changes in the kidneys, glomerulosclerosis and
      glomerulonephritis, undoubtedly contributes to and perhaps accounts for reduced
      longevity of these animals. However, GH-transgenic mice exhibit various symptoms
      of accelerated aging, including increased astrogliosis, shortened reproductive
      life span, and early onset of age-related changes in cognitive function,
      hypothalamic neurotransmitter turnover, and plasma corticosterone levels. The
      hypothesis that supraphysiological levels of GH can accelerate aging derives
      indirect support from findings in GH-deficient and GH-resistant mutant mice in
      which aging is delayed and the life-span is increased and from the reciprocal
      relationship of body size and longevity within species.

PMID- 14583654
TI  - The serotonin transporter is required for stress-evoked increases in adrenal
      catecholamine synthesis and angiotensin II AT(2) receptor expression.
AB  - High numbers of serotonin transporter (SERT) binding sites and high serotonin (5
      HT) content are expressed in the adrenal medulla of wild-type (SERT+/+) mice.
      Acute restraint stress increases adrenomedullary 5-HT, norepinephrine (NE) and
      epinephrine (E) release, adrenomedullary tyrosine hydroxylase (TH) mRNA, and
      angiotensin II AT(2) receptor expression. There are no alterations in adrenal
      catecholamine content during restraint. In littermate SERT-/- mice, which do not
      express SERT binding sites, the basal adrenomedullary 5-HT content is
      significantly reduced and does not increase after stress. The stress-induced
      increase in plasma E is higher in SERT-/- than in SERT+/+ animals. In SERT-/-
      mice, the stress-induced increase in expression of TH mRNA does not occur, and as
      a consequence, adrenal E content decreases, and adrenal E and NE content are
      lower than that of SERT+/+ mice during restraint. In addition, instead of
      increased expression, stress induces a profound decrease in the number of
      adrenomedullary AT(2) receptors in SERT-/- mice. Our results indicate that SERT
      is necessary for the stress-induced increase in adrenomedullary catecholamine
      synthesis and AT(2) receptor expression. These data further indicate a close
      relationship between the adrenomedullary 5-HT and angiotensin II systems, and an
      important role of adrenomedullary AT(2) receptors in catecholamine synthesis and
      release during stress.

PMID- 14583655
TI  - Neonatal estrogen decreases neural density of the septum-midbrain central gray
      connection underlying the lordosis-inhibiting system in female rats.
AB  - Neurons in the lateral septum (LS) with projecting axons to the midbrain central
      gray (MCG) exert an inhibitory influence on lordosis. The number of such neurons
      is greater in female than in male rats. In this experiment, effects of neonatal
      estrogen on the density of the LS-MCG connections and on lordosis behavior were
      examined in female rats. On postnatal day 4 (day 0 = day of birth), females were
      injected subcutaneously with 50 or 100 mug estradiol benzoate (EB) or oil. On
      postnatal day 60, females and control males were gonadectomized. Behavioral tests
      were carried out after the implantation of silicone tubes containing estradiol.
      Lordotic activities in both males and EB-treated females were lower than in oil
      treated females. After completing the behavioral tests, the animals were injected
      with Fluoro-Gold (FG), a retrograde tracer, into the right-side MCG and the
      number of FG-labeled neurons in the LS was measured. In all groups, the right
      side LS ipsilateral to the FG injection had more FG-labeled neurons than the left
      side LS. The number of FG-labeled neurons in the LS of oil-treated females was
      larger than that of males on both right and left sides. In the females treated
      with 100 mug EB (EB100), the number of FG-labeled neurons was comparable with
      that of males and lower than that of oil-treated females. The number of FG
      labeled neurons in the EB50 females was also lower than that in oil-treated
      females, but tended to be larger than that observed in the EB100 group. These
      results indicate that neonatal estrogen decreases both lordotic activity and the
      density of the LS-MCG neural connections in female rats.

PMID- 14583656
TI  - Sex differences in the stress-induced release of acetylcholine in the hippocampus
      and corticosterone from the adrenal cortex in rats.
AB  - To assess sex differences in stress-induced acetylcholine (ACh) release in the
      hippocampus and corticosterone (CS) release from the adrenal cortex, an in vivo
      microdialysis study was performed in intact male (n = 6) and cycling female
      (diestrus 1, n = 5; proestrus, n = 6) rats. Dialysates and blood samples were
      taken from 11.00 to 16.00 h in freely moving rats, but restraint stress was
      applied from 12.00 to 13.00 h. Basal ACh release in the hippocampus was low
      without significant differences between groups. Although ACh release promptly
      increased with the onset of restraint stress in both sexes, the magnitude of the
      increase in males was significantly greater than in female rats during diestrus
      and proestrus (p < 0.01). Basal serum CS concentrations were significantly
      greater in proestrus than in diestrus (p < 0.01) or in male rats (p < 0.01).
      Serum CS concentrations significantly increased at the onset of restraint stress
      in both sexes (p < 0.01), but the magnitude of the increase was significantly
      greater in female than in male rats (p < 0.01). These results indicate that sex
      and/or gonadal steroid environment can affect the stress-induced ACh release in
      the hippocampus and CS release from the adrenal cortex.

PMID- 14583657
TI  - Factors involved in the development of hypertension induced by a low-protein diet
      in rats with renal injury.
AB  - BACKGROUND/AIMS: While a low-protein diet (LPD) has been reported to increase
      blood pressure, the mechanism for its increase has not yet been clarified. We
      investigated the factors involved in the development of hypertension induced by
      LPD in rats with post-cyclosporine (CsA) nephropathy, and determined the
      appropriate composition for LPD that is to be utilized for renal research.
      METHODS: The rats were divided into 4 groups, each group being fed either a
      normal-protein diet (NPD), LPD with a low sucrose content as the main component
      of carbohydrate, LPD with a high-sucrose content, or LPD with low sucrose plus 2%
      L-arginine (Arg) for 12 weeks, and the blood pressure, urinary nitric oxide (NO)
      metabolite (NOx) excretion, renal NO-generating capacity and renal Arg content
      were compared among these groups. CsA was administered for the first 5 weeks to
      all groups. RESULTS: The blood pressure was significantly higher in the high
      sucrose LPD rats than in the NPD and the low-sucrose LPD rats. The supplement of
      Arg significantly decreased the blood pressure in the low-sucrose LPD rats.
      Urinary NOx, renal NO-generating capacity and the renal Arg content were
      significantly lower in the low-sucrose LPD rats than in the NPD rats. Arg
      supplementation to the LPD rats returned these values to the level of the NPD
      rats. CONCLUSION: The increase in blood pressure by LPD was associated with the
      higher amount of sucrose contained in LPD and the decrease in NO generation
      caused by the Arg depletion in rats with post-CsA nephropathy. For animal
      experiments we recommend that sucrose should not be used in LPD to balance the
      energy intake between LPD and NPD, and that a small amount of Arg be supplemented
      to LPD.

PMID- 14583658
TI  - Relative roles of nitric oxide, prostanoids and angiotensin II in the regulation
      of canine glomerular hemodynamics. A micropuncture study.
AB  - Glomerular hemodynamics are controlled by a variety of physical, nervous and
      hormonal factors including the potent vasoconstrictors, angiotensin (ANG) II and
      endothelin-1 (ET-1), and the vasodilator prostanoids (prostaglandin = PG) and
      nitric oxide (NO). Since no micropuncture data on the canine kidney exist with
      respect to the relative roles of the endogenous vasoactive hormones/autacoids NO,
      PG and ANG II in modulating glomerular hemodynamics, in the present study using
      the micropuncture technique in anesthetized dogs on a normal salt intake, we
      investigated the relative effects of these hormones/autacoids by means of the L
      arginine analog, N(omega)-nitro-L-arginine methyl ester hydrochloride (L-NAME), a
      competitive NO synthase (NOS) inhibitor, the cyclooxygenase inhibitor
      indomethacin (INDO), and the AT(1) receptor blocker EXP 3174. An intrarenal
      arterial (i.r.a.) bolus (within 5 min) of 2.5 mg of L-NAME led to a significant
      decrease in total renal blood flow (RBF) and single nephron glomerular blood flow
      (SNGBF) from 4.46 +/- 0.51 to 3.52 +/- 0.41 ml/min/g kidney weight and from 0.393
      +/- 0.041 to 0.341 +/- 0.037 microl/min (p < 0.01), respectively, without a
      change in glomerular filtration rate (GFR). The increase in arteriolar resistance
      was more pronounced at the efferent (+31%) than at the afferent (+13%) arteriole,
      and K(f) decreased from 4.5 +/- 0.5 to 3.7 +/- 0.4 nl/min/mm Hg (p < 0.01). INDO
      (5 mg/kg i.v. bolus followed by 0.17 mg/kg/min i.v.) had no effect on glomerular
      hemodynamics. EXP 3174 (30 microg/kg/min i.r.a.) increased RBF and SNGBF from
      4.35 +/- 0.45 to 4.99 +/- 0.50 ml/min/g kidney weight and from 0.403 +/- 0.028 to
      0.478 +/- 0.039 microl/min (p < 0.01), respectively, without an effect on GFR. It
      reduced the efferent arteriolar resistance by 25% as compared to 13% at the
      afferent arteriolar level. EXP 3174 increased K(f) from 5.1 +/- 0.4 to 8.1 +/-
      0.6 mm Hg (p < 0.01) in the presence of a decrease in effective filtration
      pressure from 13.2 +/- 1.7 to 8.3 +/- 1.0 mm Hg (p < 0.01). The glomerular
      hemodynamic effects of L-NAME were unaltered by pretreatment with INDO or EXP
      3174, whereas its tubular effects were restored in the presence of EXP 3174.
      Thus, from these first micropuncture data in the anesthetized dog on a normal
      sodium intake we conclude that (1) acute intrarenal inhibition of NOS by L-NAME
      decreases RBF and SNGBF due to vasoconstriction of the afferent and, more
      pronounced, efferent arterioles. Since L-NAME simultaneously decreases K(f), GFR
      remains unaltered. (2) These renal hemodynamic effects of NOS inhibition were not
      mediated by prostanoids or intrarenal ANG II. Thus, the tonic activity of
      intrarenal NOS plays an important role in maintaining glomerular hemodynamics in
      the canine kidney.

PMID- 14583660
TI  - Interaction between nitric oxide and cyclooxygenase pathways in endothelial
      cells.
AB  - Nitric oxide (NO) and cyclooxygenase (COX) derived prostaglandins (PGs) are
      involved in vascular homeostasis. Contradictory results have been obtained in
      previous studies on the putative 'cross-talk' between these two pathways. Our aim
      was to evaluate the interaction between NO and PG release in human microvascular
      endothelial cells (HMEC-1) and in umbilical vein endothelial cells (HUVEC).
      METHODS: Medium samples were assayed for nitrite/nitrate (NO(x)) and L-citrulline
      levels while lysed cells were assayed for endothelial NO synthase (eNOS), as
      markers of NO production. Prostaglandin E2 (PGE2) and 6-keto-prostaglandin
      F1alpha (6-keto-PGF1alpha) were assessed as indicators of COX activity. RESULTS:
      The NO donor sodium nitroprusside and L-arginine increased PGs levels in both
      cell types. N(G)-monomethyl-L-arginine (L-NMMA) significantly inhibited 6-keto
      PGF1alpha release without significantly reducing PGE2)levels. Indomethacin
      increased both NO(x), eNOS and L-citrulline levels. PGE2 treatment did not modify
      NO(x) values. CONCLUSION: The stimulation of PGs by NO may represent an
      additional pathway used by exogenous nitrovasodilators to elicit vasodilation.
      Reduction of PGs by inhibition of COX was compensated by enhanced NO. Conversely,
      PGs()did not compensate()decreased NO following L-NMMA treatment. Treatment with
      the vasodilatator prostaglandin E2 did not modify NO(x) levels.

PMID- 14583659
TI  - Myoendothelial gap junctions may provide the pathway for EDHF in mouse mesenteric
      artery.
AB  - Endothelium-dependent hyperpolarization of vascular smooth muscle provides a
      major pathway for relaxation in resistance arteries. This can occur due to direct
      electrical coupling via myoendothelial gap junctions (MEGJs) and/or the release
      of factors (EDHF). Here we provide evidence for the existence of functional MEGJs
      in the same, defined branches of BALB/C mouse mesenteric arteries which show
      robust EDHF-mediated smooth muscle relaxation. Cyclopiazonic acid (CPA, 10
      microM) was used to stimulate EDHF in arteries mounted under isometric conditions
      and constricted with phenylephrine. Simultaneous measurement of smooth muscle
      membrane potential and tension demonstrated that CPA caused a hyperpolarization
      of around 10 mV, reversing the depolarization to phenylephrine by 94% and the
      associated constriction by 66%. The relaxation to CPA was endothelium dependent,
      associated with the opening of Ca2+-activated K channels, and only in part due to
      the release of nitric oxide (NO). In the presence of the NO synthase inhibitor, L
      NAME (100 microM), the relaxation to CPA could be almost completely inhibited
      with the putative gap junction uncoupler, carbenoxolone (100 microM). Inhibition
      of the synthesis of prostaglandins or metabolites of arachidonic acid had no
      effect under the same conditions, and small rises in exogenous K+ failed to evoke
      consistent or marked smooth muscle relaxation, arguing against a role for these
      molecules and ions as EDHF. Serial section electron microscopy revealed a high
      incidence of MEGJs, which was correlated with heterocellular dye coupling. Taken
      together, these functional and morphological data from a defined mouse resistance
      artery suggest that the EDHF response in this vessel may be explained by
      extensive heterocellular coupling through MEGJs, enabling spread of
      hyperpolarizing current.

PMID- 14583661
TI  - Role of connective tissue growth factor in mediating hypertrophy of human
      proximal tubular cells induced by angiotensin II.
AB  - BACKGROUND/AIMS: Cellular hypertrophy is an early important pathological feature
      of renal diseases such as diabetic nephropathy and remnant kidney. Recent studies
      have demonstrated that angiotensin II (Ang II) might be a major contributor in
      regulating cell hypertrophy. However, the exact mechanism is still unclear. The
      aim of our present work was to investigate the possible role of a newly clarified
      fibrogenic factor, connective tissue growth factor (CTGF), in mediating the
      effect of Ang II-induced tubular cell hypertrophy. METHODS: The cell line HK2 was
      grown in Dulbecco's modified Eagle's medium containing 10% heat-inactivated fetal
      calf serum. After the cells were rested in serum-free medium for 24 h, the dose
      and time response of CTGF mRNA expression to Ang II stimulation was observed by
      RT-PCR, and protein synthesis was observed by Western blotting. The effect of
      anti-CTGF on Ang II (10(-7)M)-induced [(3)H]-leucine incorporation, total protein
      content (Coomassie brilliant blue G250 method) and change in cellular size
      [determined by a scanning electronic microscope (SEM)] was also observed. The
      influence of anti-CTGF antibody on the cell cycle was analyzed by using a
      fluorescence-activated cell sorter flow cytometer. RESULTS: The results showed
      that Ang II induced expression of CTGF mRNA in a time- and dose-dependent manner
      (p < 0.05 and 0.01, respectively). Stimulation of cells with Ang II (10(-7)M) for
      48 h resulted in a 92% increase in [(3)H]-leucine incorporation (5,584 cpm/10(5)
      cells at 0 h vs. 10,741 cpm/10(5) cells at 48 h; p = 0.01), which was
      significantly abolished by treatment with anti-CTGF antibody. Ang II (10(-7)M)
      significantly increased the total protein content in HK2 cells (control: 0.169 +/
      0.011 mg/10(5) cells vs. Ang II: 0.202 +/- 0.010 mg/10(5) cells; p = 0.03),
      which was markedly inhibited by cotreatment with anti-CTGF antibody. The average
      cellular diameter determined by SEM showed that the increase in cell size induced
      by Ang II could be significantly inhibited by anti-CTGF antibody (control: 11.92
      +/- 1.62 microm, Ang II group: 20.63 +/- 3.83 microm, Ang II + anti-CTGF group:
      16.43 +/- 3.23 microm; p < 0.01, respectively). Furthermore, the flow cytometer
      study showed that Ang II arrested the cell cycle at G0-G1 phase, which was
      significantly reversed by treatment with anti-CTGF antibody (G0-G1 percentage: in
      Ang II group: 76 +/- 1.8%, in Ang II + anti-CTGF group: 71 +/- 1.78%; p = 0.04).
      CONCLUSION: Our data are the first to clearly demonstrate that CTGF might be an
      important mediator of Ang II-induced renal hypertrophy, which suggests that
      inhibiting the production of CTGF might be the new strategy in early prevention
      of renal fibrosis.

PMID- 14583662
TI  - The significance of trace proteinuria.
AB  - BACKGROUND: The clinical significance of a trace protein reading on urinalysis is
      unclear, and such a result is often ignored by the clinician. METHODS: We
      examined 185 samples of urine with trace proteinuria by both Chemstrips and
      sulfosalicylic acid testing, and compared the results with those of urinary
      albumin and total protein concentrations. RESULTS: Taking for the purposes of
      this study an arbitrary upper limit of normal of 20 mg/l for albumin and 100 mg/l
      for total protein concentration, we found abnormal albumin excretion in 87% and
      abnormal total protein excretion in 88% of trace samples. In this study, a
      negative urinalysis for protein excluded microalbuminuria in 87% and proteinuria
      in 78% of cases. CONCLUSION: Qualitative testing for protein by urinalysis has a
      high sensitivity and specificity for diagnosing or ruling out microalbuminuria.
      Trace proteinuria usually means microalbuminuria; negative proteinuria tends to
      rule it out.

PMID- 14583663
TI  - Induction of cytokines and adhesion molecules in stable hemodialysis patients: is
      there an effect of membrane material?
AB  - BACKGROUND/AIMS: The aim of this study was to examine the effects of a
      biocompatible and a nonbiocompatible hemodialysis membrane on the secretion of
      cytokines and their specific antagonists as well as on the expression of adhesion
      molecules. METHODS: A crossover study using cuprophane (CU) and polysulfone (PS)
      dialyzers and measurements of serum tumor necrosis factor (TNF)-alpha, soluble
      TNF receptors, interleukin (IL)-6, IL-6 receptor, IL-2 receptor, IL-1 receptor
      antagonist and the adhesion molecules intercellular adhesion molecule 1,
      endothelial leukocyte adhesion molecule and vascular cell adhesion molecule was
      performed in 19 hemodialysis patients. 44 healthy volunteers served as controls.
      RESULTS: All of the measured cytokines and cytokine antagonists as well as all
      adhesion molecules were significantly elevated in hemodialysis patients compared
      to controls. There was a significant increase in TNF-alpha during a dialysis
      session with a CU dialyzer, but only a moderate increase using a PS dialyzer.
      None of the other cytokines and adhesion molecules were changed during a dialysis
      session. We were also able to show an upregulation of adhesion molecules in
      dialysis patients. CONCLUSION: Our study clearly demonstrates that levels of
      inflammatory cytokines as well as their antagonists and adhesion molecules are
      elevated in patients on hemodialysis therapy. Baseline values before the start of
      a dialysis session did not show any differences with regard to the usage of CU or
      PS dialysis membranes. However, CU dialyzers led to a significantly greater
      stimulation of TNF-alpha during the dialysis session in comparison to PS
      membranes, suggesting a higher degree of bioincompatibility.

PMID- 14583664
TI  - Discrepancy in the epidemiology of nondiabetic chronic renal insufficiency and
      end-stage renal disease in black and white Americans: the third National Health
      and Nutrition Examination Survey and United States Renal Data System.
AB  - BACKGROUND: Epidemiologic data regarding the prevalence of chronic renal
      insufficiency (CRI) [from the third National Health and Nutrition Examination
      Survey (NHANES III)] and the incidence of end-stage renal disease (ESRD) [from
      the United States Renal Data System (USRDS)] are available. However,
      reconciliation of these separate particulars has not been performed objectively.
      The present work examines the epidemiology of CRI of nondiabetic etiology and
      ESRD in black and white Americans aged 20 years or greater. METHODS: Based on the
      incidence of ESRD in the study population (USRDS), the numbers of subjects with
      decreased Modification of Diet in Renal Disease (MDRD) glomerular filtration rate
      (GFR) <80 ml/min/1.73 m(2), <60 ml/min/1.73 m(2) and <30 ml/ min/1.73 m(2) in
      1991 (on December 31 1991) were mathematically obtained based on a linear model
      of GFR decline. Similarly, the corresponding estimated prevalence figures of CRI
      were derived based on analyses of NHANES III data and the 1991 census counts of
      black and white Americans (aged 20 years or more). Unadjusted and adjusted
      (correcting for calibration differences between the NHANES III and MDRD
      laboratory) prevalences were calculated. Subsequently, the prevalence of
      different degrees of CRI based on the incidence of ESRD (USRDS) was compared to
      the corresponding figures of the estimated prevalence of CRI (NHANES III).
      RESULTS: By analyses of USRDS data, on December 31 1991, the prevalence of
      different degrees of reduced GFR in the study population was estimated to be as
      follows: 396,863 subjects with GFR <80 ml/min/1.73 m(2); 272,932 subjects with
      GFR <60 ml/min/1.73 m(2), and 115,065 subjects with GFR <30 ml/min/1.73 m(2).
      Using actual NHANES III creatinine values, the prevalence of different degrees of
      CRI in the study population was estimated as follows: 92,595,211 people with GFR
      <80 ml/min/1.73 m(2); 20,754,099 people with GFR <60 ml/min/1.73 m(2), and
      415,082 people with GFR <30 ml/min/1.73 m(2). The data suggest that approximately
      0.43% of subjects with GFR <80 ml/min/1.73 m(2), 1.32% of subjects with GFR <60
      ml/min/1.73 m(2) and 27.72% of subjects with GFR <30 ml/ min/1.73 m(2) reached
      ESRD (USRDS). Using adjusted NHANES III creatinine values (downwardly correcting
      the NHANES III creatinine values to account for calibration differences with the
      MDRD measurements), the prevalence of different degrees of CRI in the study
      population was estimated as follows: 28,512,939 people with MDRD GFR <80
      ml/min/1.73 m(2) (17.86%); 5,364,136 people with MDRD GFR <60 ml/min/1.73 m(2)
      (3.36%), and 255,435 people with MDRD GFR <30 ml/min/1.73 m(2) (0.16%). Of these,
      about 1.39% of the people with MDRD GFR <80 ml/min/1.73 m(2), 5.09% of the people
      with MDRD GFR <60 ml/min/1.73 m(2) and 45.07% of the people with MDRD GFR <30
      ml/min/1.73 m(2) in 1991 reached ESRD. CONCLUSION: There is a major discrepancy
      in the epidemiology of nondiabetic CRI and ESRD amongst black and white
      Americans. The reasons for this need further study.

PMID- 14583666
TI  - Gene therapy for inborn and acquired immune deficiency disorders.
AB  - Gene therapy has been under development as a way to correct inborn errors for
      over 20 years. Immune deficiencies are favorable candidates for gene therapy
      because of the potential selective advantage of genetically corrected cells in
      these conditions. Gene therapy for immune deficiencies has been the only
      application to show incontrovertible benefit in clinical trials to date. Despite
      the success in treating the underlying disease, there have been two cases of
      insertional oncogenesis reported in one of these early phase trials. Gene therapy
      approaches and clinical trials for several inborn as well as acquired immune
      deficiencies will be reviewed.

PMID- 14583665
TI  - Combined assessment of cardiac systolic dysfunction and coronary atherosclerosis
      used to predict future cardiac deaths after starting hemodialysis.
AB  - BACKGROUND/AIMS: Identification of end-stage renal disease (ESRD) patients at
      high risk for cardiac events is important for clinical dialysis management. The
      present study determined whether the combination of cardiac function and coronary
      atherosclerosis could predict future cardiac events after starting renal
      replacement therapy (RRT). METHODS: We prospectively assessed left ventricle
      ejection fraction (EF) and Gensini score (GS) using angiographic severity of
      coronary atherosclerosis in 88 consecutive ESRD patients [mean age 62 years; 69
      males (78%); 55 patients (64%) with diabetic nephropathy] at the initiation of
      RRT. EF was analyzed by echocardiogram, and GS was scored by coronary angiography
      within 3 months after starting RRT. The study end point was cardiac death. For
      analysis of the association between cardiac death and EF and GS measures, the
      univariate and multivariate Cox proportional hazards model was used. Sensitivity,
      specificity, positive predictive value (PPV) and negative predictive value, and
      accuracy of event-free prediction were evaluated. RESULTS: Twenty-four patients
      (27%) had low cardiac function (EF <50%; low EF) and 44 patients (50%) had severe
      coronary atherosclerosis (GS >15; high GS). During a follow-up period of 3 years,
      cardiac death occurred in 21 patients (24%). The PPV of low EF and high GS was 42
      and 39%, respectively; the highest PPV (53%) was obtained when low EF and high GS
      were combined. The cumulative survival rate at 5 years in patients with both low
      EF and high GS was significantly lower than those with high EF and low GS (91 vs.
      22%, p < 0.0005). CONCLUSION: The combined assessment of cardiac function and
      coronary atherosclerosis at the initiation of RRT strongly predicts future
      cardiac events.

PMID- 14583667
TI  - Gene transfer strategies for correction of lysosomal storage disorders.
AB  - Lysosomal storage diseases (LSDs) represent a large group of monogenic disorders
      of metabolism, which affect approximately 1 in 5000 live births. LSDs result from
      a single or multiple deficiency of specific lysosomal hydrolases, the enzymes
      responsible for the luminal catabolization of macromolecular substrates. The
      consequent accumulation of undigested metabolites in lysosomes leads to
      polysystemic dysfunction, including progressive neurologic deterioration, mental
      retardation, visceromegaly, blindness, and early death. In general, the residual
      amount of functional enzyme in lysosomes determines the severity and age at onset
      of the clinical symptoms, implying that even modest increases in enzyme activity
      might affect a cure. A key feature on which therapy for LSDs is based is the
      ability of soluble enzyme precursors to be secreted by one cell type and
      reinternalize by neighboring cells via receptor-mediated endocytosis and routed
      to lysosomes, where they function normally. In principle, somatic gene therapy
      could be the preferred treatment for LSDs if the patient's own cells could be
      genetically modified in vitro or in vivo to constitutively express high levels of
      the correcting enzyme and become the source of the enzyme in the patient. Both ex
      vivo and in vivo gene transfer methods have been experimented with for gene
      therapy of lysosomal disorders. Several of these methods have proved efficient
      for the transfer of genetic material into deficient cells in culture and
      reconstitution of enzyme activity. However, the same methods applied to humans or
      animal models have been giving inconsistent results, the bases of which are not
      fully understood. A broader knowledge of disease pathogenesis, facilitated by
      available, faithful animal models of LSDs, coupled to the development of better
      gene transfer systems as well as the understanding of vector host interactions
      will make somatic gene therapy for these devastating and complex diseases the
      most suitable therapeutic approach.

PMID- 14583668
TI  - Gene therapy for chronic granulomatous disease.
AB  - Identification of gene mutations responsible for leukocyte dysfunction along with
      the application of gene transfer technology has made genetic correction of such
      disorders possible. Much of the research into molecular therapy for inherited
      disorders of phagocytes has been focused on chronic granulomatous disease (CGD).
      CGD results from mutations in any one of the four genes encoding essential
      subunits of respiratory burst NADPH oxidase, the enzyme complex required for the
      production of reactive oxygen intermediates in phagocytes. The absence of
      phagocyte oxidants results in a predisposition to recurrent bacterial and fungal
      infections and inflammatory granulomas in CGD patients, associated with
      significant morbidity and mortality. Allogeneic bone marrow transplantation can
      cure CGD, but transplant-related toxicity and the limited availability of matched
      donors have restricted its wider application. Because the gene defects causing
      CGD are known, and CGD is a stem cell disorder treatable by marrow
      transplantation, CGD has emerged as a promising disease for somatic gene therapy
      targeted at the hematopoietic system. Multiple reports have demonstrated the
      reconstitution of NADPH oxidase activity by gene transfer to human CGD marrow and
      cell lines cultured in vitro. CGD mouse models have been developed by gene
      disruption, and preclinical studies on these animals using recombinant retroviral
      vectors have demonstrated reconstitution of functionally normal neutrophils and
      increased resistance to pathogens such as Aspergillus fumigatus, Burkholderia
      cepacia and Staphylococcus aureus. Although the results of these murine studies
      are encouraging, human phase-I clinical studies in CGD patients have yet to
      produce clinically beneficial numbers of corrected neutrophils for extended
      periods. Efforts to improve gene transfer efficiency into human hematopoietic
      stem cells and to increase engraftment of transduced stem cells are ongoing.

PMID- 14583669
TI  - Hematoprotection by transfer of drug-resistance genes.
AB  - Myelosuppression represents a major side effect of cytotoxic anti-cancer agents.
      Infection due to granulocytopenia and the risk of bleeding due to
      thrombocytopenia compromise the potential of curative and palliative
      chemotherapy. Considering the many chemotherapeutic agents for which drug
      resistance genes have been described, and the recent improvements in vector and
      transduction technology, it seems conceivable that drug resistance gene transfer
      into a patient's autologous hematopoietic stem or progenitor cells will be able
      to reduce or abolish chemotherapy-induced myelosuppression.

PMID- 14583670
TI  - Gene therapy targeting hematopoietic cells: better not leave it to chance.
AB  - Gene therapy targeting hematopoietic cells has arrived at a new stage of potency.
      While the potential for curing inherited disorders of the immune system has been
      demonstrated in clinical trials, we were also confronted with the first serious
      adverse events related to random insertion of foreign DNA into cellular
      chromosomes. As it is likely that the manifestation of severe side effects
      results from a multifactorial process, it will be of crucial importance to define
      the significance of the individual risk factors involved. The future of the field
      will depend on our ability to define risk classifications of clinical approaches,
      to continuously improve transgene technologies, and to introduce new concepts for
      targeted selection of transgenic cells. Interestingly, correction of genetic
      disorders by homologous gene repair in defined stem cell clones is on the
      horizon, but far from being available for clinical use.

PMID- 14583671
TI  - Adoptive immunotherapy in chimeras with donor lymphocytes.
AB  - Allogeneic stem cell transplantation has a well-defined indication in the
      treatment of hematological malignancies. The beneficial immune effect of
      allogeneic marrow transplantation has long been known, but only recently have
      methods been developed to separate the graft-versus-leukemia (GVL) effect from
      graft-versus-host disease (GVHD). Animal experiments have shown that lymphocytes
      from the marrow donor can be transfused without causing severe GVHD if stable
      chimerism and tolerance is established. First clinical studies have been
      preformed in patients with recurrent chronic myelogenous leukemia. In these
      patients complete molecular remissions were induced that persist without further
      maintenance treatment. These results have been confirmed in larger multicenter
      studies in Europe and the USA. The best results were obtained in chronic
      myelogenous leukemia (CML); repeated successes have been reported in relapsing
      acute myeloid leukemia (AML), myelodysplastic syndromes and multiple myeloma
      (MMY), and rare responses were reported for acute lymphoid leukemia. Contrary to
      animal experiments GVHD has been observed in human patients although to a lesser
      extent than expected in transplants not given immunosuppression. Secondly
      myelosuppression has been observed in patients treated with relapsing CML. In CML
      the incidence of GVHD could be reduced by depleting CD8+ T cells from the donor
      lymphocyte concentrate. Alternatively only small numbers of T lymphocytes can be
      transfused and in the case of failing responses, the numbers of donor lymphocytes
      may be increased. Results in recurrent AML have been improved by the use of low
      dose cytosine arabinoside, granulocyte-macrophage colony-stimulating factor and
      granulocyte colony-stimulating factor mobilized blood cells as compared to
      lymphocytes only. In MMY the response rate is higher than in AML, but the
      remissions are of limited duration in most patients. Several protocols have been
      designed to include preemptive donor lymphocyte transfusion in patients with a
      high relapse risk after transplantation. Problems remain to avoid chronic GVHD
      and to circumvent the immune escape mechanisms of leukemia.

PMID- 14583672
TI  - Cellular engineering of HSV-tk transduced, expanded T lymphocytes for graft
      versus-host disease management.
AB  - Engineering donor T lymphocytes with inducible 'suicide genes', such as herpes
      simplex virus thymidine kinase, has potential to improve safety and efficacy in
      allogeneic transplantation by facilitating management of graft-versus-host
      disease. Elective administration of a relatively nontoxic pro-drug would induce
      in vivo negative selection of engineered lymphocytes specifically, sparing other
      donor hematopoietic cells. The engineered cells must retain immunologic function,
      and undergo negative selection in response to clinically attainable plasma
      concentrations of pro-drug. The cell engineering process itself, typically
      involving activation, transduction, ex vivo expansion, and selection, must
      produce clinically useful numbers of genetically modified cells at high purity.
      We discuss development of a cellular engineering manufacturing process that
      yields transduced, expanded T lymphocytes meeting these requirements.

PMID- 14583673
TI  - Alternative concepts of suicide gene therapy for graft-versus-host disease after
      adoptive immunotherapy.
AB  - T-cell suicide gene therapy represents a promising novel treatment strategy for
      graft-versus-host disease following adoptive immunotherapy after allogeneic
      hematopoietic stem cell transplantation. The clinical efficiency of this approach
      is still hampered by several obstacles including induction of alloresponses due
      to the use of immunogenic suicide and selection genes, genetic inactivation of
      suicide genes, and functional immunological impairment after retroviral
      transduction with extensive in vitro stimulation. New concepts as possible
      solutions to these limitations are discussed.

PMID- 14583674
TI  - Adoptive T-cell therapy for EBV-associated post-transplant lymphoproliferative
      disease.
AB  - Increased understanding of the mechanisms by which T lymphocytes recognize virus
      and tumor-specific antigens has fueled the use of adoptive immunotherapy for
      viral and malignant diseases. An ideal candidate for such treatment is Epstein
      Barr virus (EBV). EBV-associated post-transplant lymphoproliferative disorder
      (PTLD) is a serious complication post-solid organ transplant (SOT) or
      hematopoietic stem cell transplant (HSCT). The disease is essentially the result
      of suppression of cytotoxic T-cell function and despite various treatment
      strategies the course may still be fulminant and lethal. Therefore, an adoptive
      immunotherapeutic approach using ex vivo derived EBV-specific CTL offers a
      promising solution not only for the treatment but also as prophylaxis for PTLD.
      The infusion of EBV-CTL has been demonstrated to be safe and effective in
      allogeneic HSCT recipients and their use post-SOT is being evaluated.

PMID- 14583675
TI  - Adoptive T-cell therapy for Epstein-Barr virus-positive Hodgkin's disease.
AB  - Immunotherapy approaches with antigen-specific cytotoxic T lymphocytes (CTLs)
      have proved safe and effective prophylaxis and treatment of Epstein-Barr virus
      (EBV)-associated lymphomas arising after bone marrow transplantation. EBV is also
      associated with other malignancies including about 40% of cases of Hodgkin's
      disease making this tumor another potential target for EBV-targeted
      immunotherapy. While studies with autologous EBV-specific CTLs have shown
      antiviral activity and immune effects, the clinical responses have been less
      impressive than those observed in post-transplant lymphomas. There are several
      possible reasons why the malignant cells in EBV-positive Hodgkin's disease may be
      less susceptible to immunotherapy approaches, including the fact that they
      express a more restricted array of EBV-encoded antigens and possess many immune
      evasion strategies. A number of approaches to overcome these tumor evasion
      strategies including targeting CTLs to the expressed antigens and genetic
      modification of CTLs are being evaluated.

PMID- 14583676
TI  - Chimeric T-cell receptors for the targeting of cancer cells.
AB  - Genetic engineering of human T lymphocytes to express tumor antigen-specific
      chimeric immune receptors is an attractive means for providing large numbers of
      effector cells for adoptive immunotherapy. Major mechanisms of tumor escape from
      immune recognition are efficiently bypassed. Although adoptive transfer of
      chimeric receptor-expressing peripheral blood-derived T lymphocytes has produced
      some anti-tumor activity in mice, the first clinical studies have revealed a
      disappointing lack of correlation between in vitro cytotoxicity and therapeutic
      efficacy. The most pertinent issue is that chimeric T cells fail to expand and
      rapidly lose their function in vivo. Potential strategies to enhance the
      therapeutic value of chimeric receptor-modified cells by preventing their
      functional inactivation in vivo are currently being investigated.

PMID- 14583677
TI  - Leukemia vaccines.
AB  - Evidence that immunological effector mechanisms contribute to the elimination of
      leukemic blasts in allogeneic bone marrow transplantation supports the concept
      that the immune system plays a prominent role in the control of leukemic disease.
      For patients with high-risk acute leukemia, relapse prevention in the setting of
      minimal residual disease is paramount. This review discusses vaccine strategies
      aimed to stimulate a leukemia-specific immune response in vivo.

PMID- 14583678
TI  - Effects of ABCB1 (multidrug resistance transporter) gene mutations on disposition
      and central nervous effects of loperamide in healthy volunteers.
AB  - OBJECTIVE: Mutations in the ABCB1 gene have been associated with decreased
      expression and net function of P-glycoprotein (P-gp). We investigated the
      modulation of the central nervous effects of loperamide resulting from ABCB1
      genetic variants. METHODS: On two occasions, 20 healthy volunteers received 24 mg
      loperamide suspension orally and, in a double-blind randomized two-way crossover
      fashion, 800 mg quinidine or placebo orally 1 h before loperamide. Pupil size was
      measured for 5 h following loperamide administration, and plasma concentrations
      of loperamide and quinidine were measured for 6 h. Single nucleotide
      polymorphisms and haplotypes including G2677T(A) (exon 21) and C3435T (exon 26)
      were analysed for their relation to plasma concentrations of quinidine and
      loperamide and to the miotic effects of loperamide. RESULTS: Loperamide plasma
      concentrations with quinidine co-administration were about twice as high as those
      without quinidine. The ABCB1 haplotype G2677/T3435 was associated with the
      highest loperamide plasma concentrations, which were about 1.5 times higher than
      in non-carriers of this haplotype. Plasma concentrations of quinidine did not
      differ among carriers and non-carriers of genetic variants. When quinidine was co
      administered with loperamide, pupil size decreased. Without quinidine it changed
      only minimally. The ABCB1 TT3435 genotype was associated with the most pronounced
      increase of the miotic effects of loperamide when quinidine was co-administered.
      This was accompanied by a tendency toward higher plasma loperamide in TT3435
      carriers. CONCLUSIONS: Our data support a functional importance of the ABCB1
      mutations for plasma concentrations and central nervous actions of the opioid
      loperamide.

PMID- 14583679
TI  - Association between ABCB1 (multidrug resistance transporter) genotype and post
      liver transplantation renal dysfunction in patients receiving calcineurin
      inhibitors.
AB  - OBJECTIVE: Renal dysfunction is a common and costly adverse outcome of long-term
      treatment with calcineurin inhibitors (CNIs). We conducted a retrospective, case
      control study to test whether the risk of renal dysfunction in liver
      transplantation patients receiving CNIs is associated with the 2677G>T
      transversion in exon-21 of the gene (ABCB1) encoding P-glycoprotein. A total of
      120 non-Hispanic white patients were evaluated. RESULTS: The overall incidence of
      renal dysfunction by year 3 post-transplantation was 40%. The frequency of renal
      dysfunction was reduced among patients with an ABCB1 2677TT genotype, as compared
      to those with a 2677GG genotype. Subjects with a heterozygote genotype behaved
      phenotypically like the 2677GG group. Comparing those subjects with a 2677TT
      genotype to the combined group of subjects with a 2677GG, TG, AT, or AG genotype
      resulted in an odds ratio of 0.26 (0.09-0.77). When subjects were stratified by
      gender, the frequency of renal dysfunction was reduced among men with an ABCB1
      2677TT genotype, relative to men with different genotypes. A similar odds ratio
      was obtained for women, but it did not achieve significance. When 18 subjects
      with an elevated SCr concentration just prior to surgery were excluded from the
      year 3 analysis, the association between the 2677TT genotype and chronic renal
      dysfunction in the remaining cohort was strengthened comparing genotype groups.
      CONCLUSIONS: Based on these results, we conclude that homozygosity for the ABCB1
      2677T (S893) allele is associated with reduced risk of chronic renal dysfunction
      among liver transplantation patients receiving an immunosuppressive regimen
      containing CNIs.

PMID- 14583680
TI  - ABCB1 C3435T and G2677T/A polymorphism decreased the risk for steroid-induced
      osteonecrosis of the femoral head after kidney transplantation.
AB  - Advances in transplantation technology have brought about great benefits to
      patients suffering from organ failure, but the problem still remains of
      complications induced by steroids used for post-transplant immunosuppression.
      Among the side-effects caused by steroids, non-traumatic osteonecrosis of the
      femoral head (ONF) constitutes a serious problem. The same protocol for steroid
      administration induces ONF in some patients, but not in others, indicating the
      presence of individual difference in steroid sensitivity. We hypothesized that
      this difference might be mediated by the drug-transport protein, P-glycoprotein
      (P-gp), and investigated the relationship between single nucleotide polymorphisms
      in the multidrug resistance gene 1 (ABCB1, MDR1) encoding P-gp and ONF. Subjects
      comprised 136 patients receiving kidney transplantation. Thirty patients
      developed post-transplant ONF. Genomic DNA was extracted from peripheral blood,
      and genotypes of ABCB1 C3435T (exon 26) and G2677T/A (exon 21) were determined by
      direct sequencing. Multivariate analyses based on clinical information were
      performed to determine the relationship between ABCB1 genotypes and ONF. The
      dose/concentration (D/C) ratios of tacrolimus were also determined to estimate
      the activity of P-gp in patients with different genotypes of ABCB1 C3435T (CC,
      CT, TT), and in those who did and did not develop ONF. The ABCB1 3435TT genotype
      showed a significantly lower incidence of ONF (adjusted odds ratio = 0.10, P =
      0.034). The D/C ratio in the 3435TT genotype was significantly higher than that
      in the 3435CC genotype. The D/C ratio in patients developing ONF was
      significantly higher than in those patients who did not develop ONF. The results
      suggest increased activity of P-gp in patients with the 3435TT genotype and in
      those who did not develop ONF. The ABCB1 2677 homozygous variant type also showed
      a lower incidence of ONF (adjusted odds ratio = 0.26, P = 0.056). The 3435T and
      3435C alleles were in linkage disequilibrium with the 2677T and the 2677G
      alleles, respectively, in the study population. An assessment of C3435T and
      G2677T/A polymorphisms preceding steroid treatment could be useful for predicting
      the resistance to ONF development.

PMID- 14583681
TI  - Synergistic interaction of T-786-->C polymorphism in the endothelial nitric oxide
      synthase gene and smoking for an enhanced risk for coronary spasm.
AB  - OBJECTIVE: We previously reported that a T-786-->C polymorphism in the 5'
      flanking region of the endothelial nitric oxide synthase gene and smoking were
      independently associated with coronary spasm; however, the interaction between
      this polymorphism and smoking remains to be elucidated. METHODS: We analyzed 209
      men and 238 women who were admitted consecutively at our institution; all
      subjects received an intracoronary injection of acetylcholine (ACh) while
      undergoing coronary angiography for evaluation of chest pain: all subjects had no
      significant coronary stenosis. We divided these subjects into four groups: non
      smokers with T/T genotype (Control Group A); non-smokers with C/T or C/C genotype
      (Group B); smokers with T/T genotype (Group C); and smokers with C/T or C/C
      genotype (Group D). We further examined quantitative coronary angiographies of
      the left anterior descending coronary artery in a subset of 54 consecutive men
      and 53 consecutive women. RESULTS: The frequencies of coronary spasm in Group B
      (male: 61%, female: 78%), Group C (62%, 59%) and Group D (91%, 92%) were
      significantly higher than in Group A (30%, 38%). In the males, ACh-induced
      vasoconstriction was greatest in Group D, and the change was weakest in Group A.
      In the females, ACh-induced vasoconstrictions were significantly greater in
      Groups B, C and D than in Group A. The T-786-->C polymorphism and smoking combine
      to increase the risk of coronary spasm.

PMID- 14583682
TI  - Decreased coumarin 7-hydroxylase activities and CYP2A6 expression levels in
      humans caused by genetic polymorphism in CYP2A6 promoter region (CYP2A6*9).
AB  - One of seven poor metabolizers of coumarin found in Thai subjects was previously
      genotyped as heterozygote for the CYP2A6*4 (whole deletion) and CYP2A6*9. Thus,
      we aimed to investigate the relationship between the genetic polymorphism in the
      TATA box of the CYP2A6 gene (CYP2A6*9), expression levels of CYP2A6 mRNA and
      coumarin 7-hydroxylase activities in human livers. Levels of CYP2A6 mRNA were
      quantified by real-time quantitative reverse transcriptase-polymerase chain
      reaction. The mean expression levels of CYP2A6 mRNA in individuals with
      CYP2A6*1/*4, CYP2A6*1/*9 and CYP2A6*4/*9 were 58%, 71% and 21% of the individuals
      genotyped as CYP2A6*1/*1, respectively. The mean in-vitro coumarin 7-hydroxylase
      activities in subjects carrying CYP2A6*1/*4, CYP2A6*1/*9 and CYP2A6*4/*9 were
      41%, 71% and 12%, respectively, compared to those of the subjects judged as wild
      type. Vmax values for coumarin 7-hydroxylation in the liver microsomes from human
      subjects with genotypes of CYP2A6*1/*1, CYP2A6*1/*4, CYP2A6*1/*9 and CYP2A6*4/*9
      were 0.58, 0.26, 0.44 and 0.13 nmol/min/nmol total P450, respectively. CYP2A6
      protein levels in human liver microsomes with the CYP2A6*4 and the CYP2A6*9
      alleles were markedly decreased. These results suggest that the genetic
      polymorphism in the promoter region of the CYP2A6 gene (CYP2A6*9) reduced the
      expression levels of CYP2A6 mRNA and protein in human livers, resulting in the
      decrease of coumarin 7-hydroxylase activities. Individuals judged as CYP2A6*4/*9
      were expected to be poor metabolizers, having extremely low activity of CYP2A6.

PMID- 14583683
TI  - Analysis of Sepik populations of Papua New Guinea suggests an increase of CYP2C19
      null allele frequencies during the colonization of Melanesia.
AB  - The cytochrome P450 (CYP) isozyme CYP2C19 metabolizes clinically important drugs,
      including the anti-malarial proguanil currently used for multi-drug resistant
      Plasmodium falciparum malaria. CYP2C19 activity varies among geographical regions
      due to high frequencies of two null alleles (CYP2C19*2/*3) in Asian and
      especially Pacific populations. Previously, we reported an unprecedentedly high
      frequency of CYP2C19 poor metabolizers (PM) within populations of Vanuatu, which
      suggested even higher PM frequencies in Papua New Guinea. We examined CYP2C19
      allele frequencies of three malarious populations from inland East Sepik
      Province, Papua New Guinea to evaluate this prediction and the use of proguanil
      in malaria treatment programs. These Papua New Guinean populations have PM
      frequencies intermediate between island South-east Asia and Vanuatu, most likely
      resulting from genetic drift during the settlement of the Pacific. This study
      highlights the medical consequences of population origins and the need for a
      better understanding of the genetic diversity of our global species.

PMID- 14583684
TI  - Advancing health disparities research: can we afford to ignore measurement
      issues?
AB  - BACKGROUND: Research on racial and ethnic health disparities in the United States
      requires that self-report measures, developed primarily in mainstream samples,
      are appropriate when applied in diverse groups. To compare groups, mean scores
      must reflect true scores and have minimal bias, assumptions that have not been
      tested for many self-report measures used in this research. OBJECTIVE: To
      identify conceptual and psychometric issues that need to be addressed to assure
      the quality of self-report measures being used in health disparities research.
      METHODS: We present 2 broad conceptual frameworks for health disparities research
      and describe the main research questions and measurement issues for 4 key
      concepts hypothesized as potential mechanisms of health disparities:
      socioeconomic status, discrimination, acculturation, and quality of care. This
      article is based on a small conference convened by 6 Resource Centers for
      Minority Aging Research (RCMAR) measurement cores. We integrate written materials
      prepared for the conference by quantitative and qualitative measurement
      specialists and cross-cultural researchers, conference discussions, and current
      literature. RESULTS: Problems in the quality of the conceptualizations and
      measures were found for all 4 concepts, and little is known about the extent to
      which measures of these concepts can be interpreted similarly across diverse
      groups. Many problems also apply to other concepts relevant to health
      disparities. We propose an agenda for accomplishing this challenging measurement
      research. CONCLUSIONS: The current national commitment to reduce health
      disparities may be compromised without more research on measurement quality.
      Integrated, systematic efforts are needed to move this work forward, including
      collaborative efforts and special initiatives.

PMID- 14583685
TI  - Racial disparities in diabetes care processes, outcomes, and treatment intensity.
AB  - BACKGROUND: Black Americans with diabetes have a higher burden of illness and
      mortality than do white Americans. However, the extent to which differences in
      medical care processes and treatment intensity contribute to poorer diabetes
      outcomes is unknown. OBJECTIVE: To assess racial disparities in the quality of
      diabetes care processes, intermediate outcomes, and treatment intensity. METHODS:
      We conducted an observational study of 801 white and 115 black patients who
      completed the Diabetes Quality Improvement Project survey (response rate=72%) in
      21 Veterans Affairs (VA) facilities using survey data; medical record information
      on receipt of diabetes services (A1c, low-density lipoprotein [LDL], nephropathy
      screen, and foot and dilated eye examinations), and intermediate outcomes
      (glucose control measured by A1c; cholesterol control measured by LDL; and
      achieved level of blood pressure); and pharmacy data on filled prescriptions.
      RESULTS: There were no racial differences in receipt of an A1c test or foot
      examination. Blacks were less likely than whites to have LDL checked in the past
      2 years (72% vs. 80%, P<0.05) and to have a dilated eye examination (50% vs. 63%,
      P<0.01). Even after adjusting for patients' age, education, income, insulin use,
      diabetes self-management, duration, severity, comorbidities, and health services
      utilization, racial disparities in receipt of an LDL test and eye examination
      persisted. After taking into account the nested structure of the data using a
      random intercepts model, blacks remained significantly less likely to have LDL
      testing than whites who received care within the same facility (68% vs. 83%,
      P<0.01). In contrast, there were no longer differences in receipt of eye
      examinations, suggesting that black patients were more likely to be receiving
      care at facilities with overall lower rates of eye examinations. After adjusting
      for patient characteristics and facility effects, black patients were
      substantially more likely than whites to have poor cholesterol control (LDL > or
      =130) and blood pressure control (BP > or =140/90 mm Hg) (P<0.01). Among those
      with poor blood pressure and lipid control, blacks received as intensive
      treatment as whites for these conditions. CONCLUSIONS: We found racial
      disparities in some diabetes care process and intermediate outcome quality
      measures, but not in intensity of treatment for those patients with poor control.
      Disparities in receipt of eye examinations were the result of black patients
      being more likely to receive care at lower-performing facilities, whereas for
      other quality measures, racial disparities within facilities were substantial.

PMID- 14583687
TI  - Race and gender disparities in rates of cardiac revascularization: do they
      reflect appropriate use of procedures or problems in quality of care?
AB  - BACKGROUND: Numerous studies have documented substantial differences by race and
      gender in the use of coronary artery bypass graft surgery and percutaneous
      coronary angioplasty. However, few studies have examined whether these
      differences reflect problems in quality of care. METHOD: We selected a random
      sample stratified by gender, race, and income of 5026 Medicare beneficiaries aged
      65 to 75 who underwent inpatient coronary angiography during 1991 to 1992 in 1 of
      5 states. We compared the frequency of 2 problems in quality by race and gender:
      underuse or the failure to receive a clinically indicated revascularization
      procedure and receipt of revascularization when it was not clinically indicated.
      We used 2 independent sets of criteria developed by the RAND Corporation and the
      American College of Cardiology/American Hospital Association (ACC/AHA). We also
      examined survival of the cohort through March 31, 1994. RESULTS:
      Revascularization procedures were clinically indicated more frequently among
      whites than blacks and among men than women. Failure to receive revascularization
      when it was indicated was more common among blacks than among whites (40% vs. 23
      24%, depending on the criteria, both P<0.001) but similar among men and women
      (25% vs. 22-24%, P>0.05). Racial disparities remained similar after adjusting for
      patient and hospital characteristics. Among patients rated inappropriate, use of
      procedures was greater for whites than blacks using RAND criteria (10.5% vs.
      5.8%, P<0.01) and greater for men than for women (14.2% vs. 5.3% by RAND
      criteria, P=0.001; 8.2% vs. 4.0%% by ACC/AHA criteria, P=0.04). After
      multivariate adjustment, the disparities for race and gender remained similar and
      were statistically significant using RAND criteria. Mortality rates tended to
      validate our appropriateness criteria for underuse. CONCLUSIONS: Racial
      differences in procedure use reflect higher rates of clinical appropriateness
      among whites, greater underuse among blacks, and more frequent revascularization
      when it was not clinically indicated among whites. Underuse is associated with
      higher mortality. In contrast, men had higher rates of clinical appropriateness
      and were more likely to receive revascularization when it was not clinically
      indicated. There was no evidence of greater underuse among women.

PMID- 14583686
TI  - The association of race/ethnicity with the receipt of traditional and alternative
      arthritis-specific health care.
AB  - BACKGROUND: The role of race/ethnicity in the receipt of arthritis-specific
      health care has not been well defined. OBJECTIVE: To examine the association of
      race/ethnicity with the utilization of arthritis health care among community
      dwelling older adults. RESEARCH DESIGN: We used a computer-assisted telephone
      interview. SUBJECTS: A population-based random sample was drawn from 6
      preselected Alabama counties. Eligible respondents had self-reported arthritis
      and were over 50 years of age; 1424 people responded to the survey. MEASURES:
      Logistic regression was used to examine the association of race/ethnicity with
      the use of conventional (including use of a rheumatologist, primary care
      physician, and prescription arthritis medicines) and complementary and
      alternative medicines (CAM), including the use of chiropractic care, glucosamine
      and/or chondroitin, and herbals. RESULTS: Reflecting stratified sampling,
      respondents were white (n=852, 60%) or black (n=528, 37%), female (72%), and had
      a mean age of 65 years. After multivariable adjustment, race/ethnicity was not a
      significant determinant of receiving rheumatology care or prescription arthritis
      medicines. However, whites were more likely than blacks to have seen a primary
      care physician for arthritis care (adjusted odds ratio [OR], 1.49; 95% confidence
      interval [CI], 1.12-1.98) or to have used CAM (OR, 1.47; 95% CI, 1.13-1.91) and
      twice as likely to have used glucosamine and/or chondroitin (OR, 1.99; 95% CI,
      1.30-3.05). CONCLUSION: In this population of community-dwelling older adults,
      white race was significantly associated with CAM use and visits to primary care
      physicians for arthritis care. In contrast, the use of specialists and
      prescription arthritis medications was better explained by factors other than
      race/ethnicity, which included female gender, urban residence, higher educational
      level, and other arthritis-specific variables.

PMID- 14583688
TI  - Racial variations in dental procedures: the case of root canal therapy versus
      tooth extraction.
AB  - BACKGROUND: Racial disparities have been widely documented in medical care, but
      variations in dental care have not been well examined. OBJECTIVES: To determine
      if there is racial variation in use of root canal therapy versus tooth extraction
      across different levels of dental insurance coverage and adjusting for other
      factors known to influence treatment decisions. METHODS: Within 3 different
      categories of insurance coverage, we examined whether there were racial
      differences in the provision of the tooth-sparing treatment of root canal therapy
      (vs. tooth extraction) among 54,423 users of outpatient Veterans Affairs dental
      care in 1998. Regression analyses adjusted for the severity of tooth- and gum
      related disease, age, sex, medical and psychiatric comorbidities, prior use of
      preventive dental services, tooth extraction and root canal therapy, and
      clustering by geographic region. RESULTS: In the adjusted regression models,
      black patients and those with unknown race were less likely overall to receive
      root canal therapy than whites, whereas Asians were more likely. Among patients
      with eligibility for continuing and comprehensive dental care, blacks were less
      likely and Asians more likely to receive root canals than whites. For patients
      covered only for emergency dental care, Hispanics had a higher likelihood of
      receiving root canal therapy. Among all other types of coverage, there were no
      significant racial differences in the care received. CONCLUSION: We observed
      substantial racial variations in the provision of root canal therapy among
      patients treated in Department of Veterans Affairs dental clinics. Future
      research should identify the causes of such variations.

PMID- 14583689
TI  - Health-related quality of life in a multiethnic sample of middle-aged women:
      Study of Women's Health Across the Nation (SWAN).
AB  - BACKGROUND: Relatively little is known about the association between menopause
      and health-related quality of life (HRQL) across ethnic groups. OBJECTIVES: To
      examine the association between HRQL and early perimenopause and ethnicity,
      adjusting for health, lifestyle, psychosocial, and sociodemographic factors.
      RESEARCH DESIGN: Questionnaires were administered to pre- and early
      perimenopausal women. SUBJECTS: We studied a cohort of 3302 black, Chinese,
      Hispanic, Japanese, and white women aged 42 to 52 years from the multisite Study
      of Women's Health Across the Nation (SWAN). MEASURES: We measured HRQL, menstrual
      regularity, and a variety of covariates. HRQL was assessed with 5 subscales from
      the Short Form-36; impaired functioning was defined as being in the 25% most
      impaired on a subscale. RESULTS: In unadjusted, but not adjusted, analyses,
      significantly more early perimenopausal women, as compared with premenopausal
      women, were classified as having impaired functioning on each of the 5 subscales.
      For 4 of the subscales, the effect of menopausal status was explained by
      menopause-related symptoms. There were significant ethnic group differences
      across all 5 subscales in unadjusted analyses. Ethnicity was no longer
      significant for the Vitality or Role-Emotional subscales when adjusted for health
      variables or for the Role-Physical subscale when analyses were adjusted for
      socioeconomic status, health, lifestyle, or social circumstances. Ethnicity
      remained significant for the Bodily Pain and Social Functioning subscales, even
      in adjusted analyses. CONCLUSIONS: Early perimenopause is not associated with
      impaired functioning when adjusted for symptoms. Significant ethnic differences
      in HRQL exist. Some, but not all, differences can be explained by differences in
      health, lifestyle, and social circumstances.

PMID- 14583690
TI  - Mapping the SF-12 to preference-based instruments: convergent validity in a low
      income, minority population.
AB  - BACKGROUND: The profile-based SF-12 has a low respondent burden and is used
      widely in clinical settings to monitor health and evaluate programs. Deriving
      preference scores for the SF-12 health profile would permit its use in cost
      effectiveness analyses. Previous mapping studies of SF family instruments to
      preference-based instruments have not examined convergent validity or performance
      in low-income, minority populations. OBJECTIVES: To map the SF-12 to the EuroQol
      (EQ-5D Index) and the Health Utilities Index Mark 3 (HUI3) in a low-income,
      predominantly minority sample. RESEARCH DESIGN: We used a cross-sectional survey
      data. SUBJECTS: We studied a convenience sample of 240 low-income, predominantly
      Latino and black patients attending a community health center in New York.
      MEASURES: We used separate regressions of the EQ-5D Index and HUI3 onto the
      physical (PCS-12) and mental (MCS-12) components of the SF-12 scores as measures.
      RESULTS: For the EQ-5D Index regression, the adjusted variance explained was 58%
      (bootstrap validation 95% confidence interval [CI], 46-66). For the HUI3
      regression, the adjusted variance explained was 51% (bootstrap 95% CI, 39-59).
      The correlation coefficient between the 2 predicted measures was 0.96. The
      correlation of the predicted HUI3 with the EQ-5D Index (0.73) and the predicted
      EQ-5D Index with the HUI3 (0.70) exceeded that between the 2 original preference
      based measures themselves (0.69). CONCLUSIONS: These pilot results suggest that
      the SF-12 could be successfully mapped to both the EQ-5D Index and HUI3, yielding
      preference-based scores that demonstrate convergent validity in a low-income,
      minority sample.

PMID- 14583691
TI  - The Patient Health Questionnaire-2: validity of a two-item depression screener.
AB  - BACKGROUND: A number of self-administered questionnaires are available for
      assessing depression severity, including the 9-item Patient Health Questionnaire
      depression module (PHQ-9). Because even briefer measures might be desirable for
      use in busy clinical settings or as part of comprehensive health questionnaires,
      we evaluated a 2-item version of the PHQ depression module, the PHQ-2. METHODS:
      The PHQ-2 inquires about the frequency of depressed mood and anhedonia over the
      past 2 weeks, scoring each as 0 ("not at all") to 3 ("nearly every day"). The PHQ
      2 was completed by 6000 patients in 8 primary care clinics and 7 obstetrics
      gynecology clinics. Construct validity was assessed using the 20-item Short-Form
      General Health Survey, self-reported sick days and clinic visits, and symptom
      related difficulty. Criterion validity was assessed against an independent
      structured mental health professional (MHP) interview in a sample of 580
      patients. RESULTS: As PHQ-2 depression severity increased from 0 to 6, there was
      a substantial decrease in functional status on all 6 SF-20 subscales. Also,
      symptom-related difficulty, sick days, and healthcare utilization increased.
      Using the MHP reinterview as the criterion standard, a PHQ-2 score > or =3 had a
      sensitivity of 83% and a specificity of 92% for major depression. Likelihood
      ratio and receiver operator characteristic analysis identified a PHQ-2 score of 3
      as the optimal cutpoint for screening purposes. Results were similar in the
      primary care and obstetrics-gynecology samples. CONCLUSION: The construct and
      criterion validity of the PHQ-2 make it an attractive measure for depression
      screening.

PMID- 14583692
TI  - Waiting time, doctor shopping, and nonattendance at specialist outpatient
      clinics: case-control study of 6495 individuals in Hong Kong.
AB  - OBJECTIVE: Nonattendance is a major health services research and management issue
      that has received little attention or systematic study in Asia. We examined the
      independent associations between waiting time, doctor shopping, and nonattendance
      in specialist outpatient clinics of 4 large public hospitals in Hong Kong.
      RESEARCH DESIGN: Case-control study. SETTING AND PARTICIPANTS: A total of 6495
      attenders and nonattenders enrolled from July 2000 through October 2001. PAIN
      OUTCOME MEASURES: Odds ratios (ORs) and associated 95% confidence intervals (CI)
      for nonattendance. RESULTS: Longer waiting times (adjusted OR2nd quartile, 1.67;
      95% CI, 1.38-2.03; adjusted OR3rd quartile, 1.90; 95% CI, 1.56-2.30; adjusted
      OR4th quartile, 2.30; 95% CI, 1.91-2.78) and doctor-shopping behavior (adjusted
      OR, 2.91; 95% CI, 2.51-3.38) were independent risk factors for nonattendance.
      These effects were robust after multivariate adjustment and testing for effect
      modification. They also appeared to persist uniformly across hospitals and
      specialties. There was no demonstrable relationship between waiting time and
      doctor shopping. CONCLUSIONS: This is the largest study of nonattendance at
      outpatient clinics and the first such study carried out in Asia. Targeted
      strategies should be implemented and evaluated using these results to reduce
      waiting time, doctor shopping, and ultimately nonattendance.

PMID- 14583693
TI  - Using risk-adjustment models to identify high-cost risks.
AB  - BACKGROUND: We examine the ability of various publicly available risk models to
      identify high-cost individuals and enrollee groups using multi-HMO administrative
      data. METHODS: Five risk-adjustment models (the Global Risk-Adjustment Model
      [GRAM], Diagnostic Cost Groups [DCGs], Adjusted Clinical Groups [ACGs], RxRisk,
      and Prior-expense) were estimated on a multi-HMO administrative data set of 1.5
      million individual-level observations for 1995-1996. Models produced
      distributions of individual-level annual expense forecasts for comparison to
      actual values. Prespecified "high-cost" thresholds were set within each
      distribution. The area under the receiver operating characteristic curve (AUC)
      for "high-cost" prevalences of 1% and 0.5% was calculated, as was the proportion
      of "high-cost" dollars correctly identified. Results are based on a separate
      106,000-observation validation dataset. MAIN RESULTS: For "high-cost" prevalence
      targets of 1% and 0.5%, ACGs, DCGs, GRAM, and Prior-expense are very comparable
      in overall discrimination (AUCs, 0.83-0.86). Given a 0.5% prevalence target and a
      0.5% prediction threshold, DCGs, GRAM, and Prior-expense captured $963,000
      (approximately 3%) more "high-cost" sample dollars than other models. DCGs
      captured the most "high-cost" dollars among enrollees with asthma, diabetes, and
      depression; predictive performance among demographic groups (Medicaid members,
      members over 64, and children under 13) varied across models. CONCLUSIONS: Risk
      models can efficiently identify enrollees who are likely to generate future high
      costs and who could benefit from case management. The dollar value of improved
      prediction performance of the most accurate risk models should be meaningful to
      decision-makers and encourage their broader use for identifying high costs.

PMID- 14583696
TI  - Hybrid heroes.

PMID- 14583694
TI  - Self-management behavior.

PMID- 14583697
TI  - Yellow alert: a color for every situation.

PMID- 14583698
TI  - Teacher, clinician ... friend. Tributes to Peter Safar.

PMID- 14583699
TI  - EMS shines through NE blackout.

PMID- 14583700
TI  - The new toy.

PMID- 14583702
TI  - 2003 JEMS EMS salary & workplace survey: the slow steady climb.

PMID- 14583703
TI  - Emergency medical dispatch: no longer the 'weak link'?

PMID- 14583704
TI  - Nerve agent attack: a dangerous threat to emergency responders & the public.

PMID- 14583705
TI  - Blood disorders: sickle cell disease & leukemia--more similar than you may think.

PMID- 14583707
TI  - The homeland security communications mistake.

PMID- 14583709
TI  - Bumper statements.

PMID- 14583712
TI  - Ten things I wish I'd known.

PMID- 14583713
TI  - If you're not outraged, you're not paying attention.

PMID- 14583714
TI  - A 21-year-old man with pneumothorax, subcutaneous emphysema, and a persistent air
      leak after chest tube insertion.

PMID- 14583716
TI  - Emergency nursing: historical, current, and future roles.
AB  - Building upon a historical context, the current and future roles of the clinical
      emergency nurse are reviewed. For several reasons, emergency nurse availability
      is expected to be insufficient to meet staffing demands in the near future.
      Emergency physicians can partner with emergency nurses and hospital
      administrators to pursue the following strategies for addressing the nursing
      shortage: (1) improve the workplace environment by improving nurse-to-patient
      ratios and avoiding the boarding of admitted patients in the emergency department
      (ED); (2) refocus the emergency nurse job description to patients and their
      families; (3) promote mutually supportive relationships and comradeship between
      emergency nurses and physicians; (4) create an environment that allows unique
      solutions to staff scheduling and accommodates shiftwork; (5) increase nursing
      wages, and recognize special contributions of emergency nurses with financial
      reward; (6) identify and promote the personnel of the hospital ED as members of
      an elite unit; (7) develop preceptorships and internships for nurses new to
      emergency nursing and invest in clinical specialists or nurse-mentors to assist
      in "on-the-job" instruction of nurses with previous experience; and (8) invest in
      nursing education. Taking these steps today will strengthen the ED health care
      safety net for decades to come.

PMID- 14583715
TI  - What is the best topical anesthetic for nasogastric insertion? A comparison of
      lidocaine gel, lidocaine spray, and atomized cocaine.
AB  - INTRODUCTION: Nasogastric intubation has been shown to be a painful procedure for
      patients. Previous studies have demonstrated the benefit of topical nasal
      anesthesia in decreasing the pain of this procedure. This study attempts to
      identify which of 3 topical anesthetic modalities would be preferred by patients.
      METHODS: This study had a double-blind, double-dummy randomized triple crossover
      design with 30 healthy volunteers as participants. Each participant had 3
      nasogastric tubes inserted and acted as his or her own control for the 3 study
      medications: 1.5 mL 4% atomized lidocaine, 1.5 mL 4% atomized cocaine, and 5 mL
      2% lidocaine gel. Participants scored pain of tube passage through the nostril as
      well as global discomfort. They were also asked to identify which agent they
      preferred. RESULTS: In our 30 subjects, although no statistically significant
      difference in nasal pain scores was found, "global discomfort" was less with the
      lidocaine gel (P =.017). Participants preferred the lidocaine gel over atomized
      cocaine (P <.00), but not to a statistically significant degree. DISCUSSION: Two
      percent lidocaine gel appeared to provide the best option for a topical
      anesthetic during nasogastric tube insertion.

PMID- 14583717
TI  - MDMA (Ecstasy) in the emergency department.

PMID- 14583718
TI  - Verification of endotracheal tube placement: a comparison of confirmation
      techniques and devices.

PMID- 14583719
TI  - Knowledge assessment and preparation for the Certified Emergency Nurses
      examination.

PMID- 14583720
TI  - Tricks for the ED trade.

PMID- 14583722
TI  - How to protect your "coconut": a safety demonstration on the importance of
      wearing a ski helmet.

PMID- 14583727
TI  - A statewide ED nursing course for new graduates or nurses without ED experience:
      using a traditional approach/interactive videoconference technology.

PMID- 14583728
TI  - A 4-week-old infant with cyanosis and dehydration.

PMID- 14583729
TI  - Mushrooms: toxins right in your own backyard.

PMID- 14583730
TI  - Should access to emergency departments be limited for "frequent fliers"?

PMID- 14583731
TI  - Knee dislocation with an arterial injury: a case study.

PMID- 14583732
TI  - A 38-year-old man with generalized weakness, bilateral ptosis, stiff neck, and
      shortness of breath.

PMID- 14583733
TI  - The winning channels.

PMID- 14583734
TI  - The nuts and bolts of IRF structure.

PMID- 14583735
TI  - Dawdling polymerases allow introns time to splice.

PMID- 14583736
TI  - Repairing nucleosomes during transcription.

PMID- 14583737
TI  - Filming bacteria.

PMID- 14583738
TI  - Phylogenomics of the nucleosome.
AB  - Histones are best known as the architectural proteins that package the DNA of
      eukaryotic organisms, forming octameric nucleosome cores that the double helix
      wraps tightly around. Although histones have traditionally been viewed as slowly
      evolving scaffold proteins that lack diversification beyond their abundant tail
      modifications, recent studies have revealed that variant histones have evolved
      for diverse functions. H2A and H3 variants have diversified to assume roles in
      epigenetic silencing, gene expression and centromere function. Such
      diversification of histone variants and 'deviants' contradicts the perception of
      histones as monotonous members of multigene families that indiscriminately
      package and compact the genome. How these diverse functions have evolved from
      ancestral forms can be addressed by applying phylogenetic tools to increasingly
      abundant sequence data.

PMID- 14583739
TI  - Activation of alpha2 adrenergic receptors suppresses fear conditioning:
      expression of c-Fos and phosphorylated CREB in mouse amygdala.
AB  - alpha(2) adrenergic agonists such as dexmedetomidine generally suppress
      noradrenergic transmission and have sedative, analgesic, and antihypertensive
      properties. Considering the importance of the neurotransmitter norepinephrine in
      forming memories for fearful events, we have investigated the acute and chronic
      effects of dexmedetomidine on discrete cue and contextual fear conditioning in
      mice. When administered before training, dexmedetomidine (10-20 microg/kg, i.p.)
      selectively suppressed discrete cue fear conditioning without affecting
      contextual memory. This behavioral change was associated with a decrease in
      memory retrieval-induced expression of c-Fos and P-CREB in the lateral,
      basolateral, and central nuclei of the amygdala. Dexmedetomidine's action on
      discrete cue memory did not occur in alpha(2A) adrenoceptor knockout (KO) mice.
      When dexmedetomidine was administered after training, it suppressed contextual
      memory, an effect that did not occur in alpha(2A) adrenoceptor KO mice. We
      conclude that dexmedetomidine, acting at alpha(2A) adrenoceptors, must be present
      during the encoding process to decrease discrete cue fear memory; however, its
      ability to suppress contextual memory is likely the result of blocking the
      consolidation process. The ability of alpha(2) agonists to suppress fear memory
      may be a valuable property clinically in order to suppress the formation of
      memories during stressful situations.

PMID- 14583740
TI  - A pilot study of risperidone, olanzapine, and haloperidol in psychotic youth: a
      double-blind, randomized, 8-week trial.
AB  - This pilot study was undertaken to estimate the acute antipsychotic effect size
      and side effect propensity of risperidone and olanzapine in the pediatric
      population, in comparison to haloperidol, a conventional antipsychotic with
      established efficacy. Risperidone and olanzapine are widely used as first-line
      treatments to ameliorate psychotic symptoms in youth, but their abilities to
      specifically treat children and adolescents presenting due to psychotic symptoms
      have not been rigorously studied. Subjects, selected because of prominent
      positive psychotic symptoms, were randomly assigned to double-blind, parallel
      treatment with risperidone, olanzapine, or haloperidol for 8 weeks. The primary
      outcome was reduction in the Brief Psychiatric Rating Scale for Children total
      score from baseline to termination. An exploratory, descriptive analysis was done
      to compare the three treatments. A total of 50 patients, 8-19 years,
      participated. All treatments reduced symptoms significantly with p-values
      (corrected for multiple comparisons) of 0.0018 for each of the atypical agents
      and 0.012 for haloperidol. In all, 88% of subjects treated with olanzapine, 74%
      treated with risperidone, and 53% treated with haloperidol met response criteria.
      The primary side effects observed in all patients were mild to moderate sedation,
      extrapyramidal symptoms, and weight gain. Risperidone and olanzapine acutely
      reduced psychotic symptoms in this pediatric sample. Exploratory comparisons
      indicate the magnitude of the antipsychotic response with these atypical agents
      is comparable to that observed with haloperidol. However, youth treated with
      risperidone and olanzapine experienced weight gain and extrapyramidal effects
      that appear more prevalent and severe than reported in adults.

PMID- 14583741
TI  - Decreasing amphetamine-induced dopamine release by acute phenylalanine/tyrosine
      depletion: A PET/[11C]raclopride study in healthy men.
AB  - Acute phenylalanine/tyrosine depletion (APTD) has been proposed as a new method
      to decrease catecholamine neurotransmission safely, rapidly, and transiently.
      Validation studies in animals are encouraging, but direct evidence in human brain
      is lacking. In the present study, we tested the hypothesis that APTD would reduce
      stimulated dopamine (DA) release, as assessed by positron emission tomography
      (PET) and changes in [(11)C]raclopride binding potential (BP), a measure of DA
      D2/D3 receptor availability. Eight healthy men received two PET scans, both
      following d-amphetamine, 0.3 mg/kg, p.o., an oral dose known to decrease
      [(11)C]raclopride BP in ventral striatum. On the morning before each scan,
      subjects ingested, in counter-balanced order, an amino-acid mixture deficient in
      the catecholamine precursors, phenylalanine, and tyrosine, or a nutritionally
      balanced mixture. Brain parametric images were generated by calculating
      [(11)C]raclopride BP at each voxel. BP values were extracted from the t-map
      (threshold: t=4.2, equivalent to p<0.05, Bonferroni corrected) and a priori
      identified regions of interest from each individual's coregistered magnetic
      resonance images. Both receptor parametric mapping and region of interest
      analyses indicated that [(11)C]raclopride binding was significantly different on
      the two test days in the ventral striatum (peak t=6.31; x=-25, y=-8, and z=0.1).
      In the t-map defined cluster, [(11)C]raclopride BP values were 11.8+/-11.9%
      higher during the APTD session (p<0.05). The reduction in d-amphetamine-induced
      DA release exhibited a linear association with the reduction in plasma tyrosine
      levels (r=-0.82, p<0.05). Together, the results provide the first direct evidence
      that APTD decreases stimulated DA release in human brain. APTD may be a suitable
      new tool for human neuropsychopharmacology research.

PMID- 14583742
TI  - Anxiogenic effect of cholecystokinin in the dorsal periaqueductal gray.
AB  - Systemic administration of cholecystokinin (CCK) fragments produces anxiogenic
      effects. The dorsal periaqueductal gray (dPAG) has been related to anxiety and
      panic reactions. The objective of this study was to investigate a possible
      anxiogenic effect of CCK-8 microinjected into the dPAG. At 10 min after the last
      microinjection (0.5 microl) into the dPAG male Wistar rats (N=7-17) were tested
      in the elevated plus-maze, an animal model of anxiety. The following treatments
      were tested alone or in combination: sulfated CCK-8 (CCK-8s, 0.5-1 microg), PD
      135158 (N-methyl-D-glucamine, 0.1 microg), a CCK-2 receptor antagonist,
      lorglumide (0.1-0.3 microg), a CCK-1 receptor antagonist. In addition, Fos
      immunohistochemistry was performed in rats (n=3-4) treated with CCK-8s (1 microg)
      alone or in combination with PD 135158 (0.1 microg). CCK-8s produced anxiogenic
      like effect, decreasing the percentage of time spent in open arm (saline=30.3+/
      6.6, CCK 0.5 microg=15.2+/-1.8; CCK 1 microg=14.6+/-2.1). This effect was
      prevented by pretreatment with PD 135158, but not by lorglumide. CCK-8s injected
      into the dPAG induced Fos immunoreactivity in several brain areas related to
      defensive behavior, including the PAG, median, and dorsal raphe nuclei, superior
      colliculus, lateral septal nuclei, medial hypothalamus, and medial amygdala. This
      effect was also prevented by pretreatment with PD 135,158. These results suggest
      that CCK-8s, acting on CCK-2 receptors, may modulate anxiety reactions in the
      dPAG.

PMID- 14583744
TI  - Effects of cannabidiol (CBD) on regional cerebral blood flow.
AB  - Animal and human studies have suggested that cannabidiol (CBD) may possess
      anxiolytic properties, but how these effects are mediated centrally is unknown.
      The aim of the present study was to investigate this using functional
      neuroimaging. Regional cerebral blood flow (rCBF) was measured at rest using
      (99m)Tc-ECD SPECT in 10 healthy male volunteers, randomly divided into two groups
      of five subjects. Each subject was studied on two occasions, 1 week apart. In the
      first session, subjects were given an oral dose of CBD (400 mg) or placebo, in a
      double-blind procedure. SPECT images were acquired 90 min after drug ingestion.
      The Visual Analogue Mood Scale was applied to assess subjective states. In the
      second session, the same procedure was performed using the drug that had not been
      administered in the previous session. Within-subject between-condition rCBF
      comparisons were performed using statistical parametric mapping (SPM). CBD
      significantly decreased subjective anxiety and increased mental sedation, while
      placebo did not induce significant changes. Assessment of brain regions where
      anxiolytic effects of CBD were predicted a priori revealed two voxel clusters of
      significantly decreased ECD uptake in the CBD relative to the placebo condition
      (p<0.001, uncorrected for multiple comparisons). These included a medial temporal
      cluster encompassing the left amygdala-hippocampal complex, extending into the
      hypothalamus, and a second cluster in the left posterior cingulate gyrus. There
      was also a cluster of greater activity with CBD than placebo in the left
      parahippocampal gyrus (p<0.001). These results suggest that CBD has anxiolytic
      properties, and that these effects are mediated by an action on limbic and
      paralimbic brain areas.

PMID- 14583745
TI  - Mapping the mouse brain.

PMID- 14583743
TI  - Gender-specific gene expression in post-mortem human brain: localization to sex
      chromosomes.
AB  - Gender differences in brain development and in the prevalence of neuropsychiatric
      disorders such as depression have been reported. Gender differences in human
      brain might be related to patterns of gene expression. Microarray technology is
      one useful method for investigation of gene expression in brain. We investigated
      gene expression, cell types, and regional expression patterns of differentially
      expressed sex chromosome genes in brain. We profiled gene expression in male and
      female dorsolateral prefrontal cortex, anterior cingulate cortex, and cerebellum
      using the Affymetrix oligonucleotide microarray platform. Differentially
      expressed genes between males and females on the Y chromosome (DBY, SMCY, UTY,
      RPS4Y, and USP9Y) and X chromosome (XIST) were confirmed using real-time PCR
      measurements. In situ hybridization confirmed the differential expression of
      gender-specific genes and neuronal expression of XIST, RPS4Y, SMCY, and UTY in
      three brain regions examined. The XIST gene, which silences gene expression on
      regions of the X chromosome, is expressed in a subset of neurons. Since a subset
      of neurons express gender-specific genes, neural subpopulations may exhibit a
      subtle sexual dimorphism at the level of differences in gene regulation and
      function. The distinctive pattern of neuronal expression of XIST, RPS4Y, SMCY,
      and UTY and other sex chromosome genes in neuronal subpopulations may possibly
      contribute to gender differences in prevalence noted for some neuropsychiatric
      disorders. Studies of the protein expression of these sex-chromosome-linked genes
      in brain tissue are required to address the functional consequences of the
      observed gene expression differences.

PMID- 14583747
TI  - Maintaining stability in the face of change.

PMID- 14583748
TI  - Food for thought: a receptor finds its ligand.

PMID- 14583749
TI  - Exciting guts with GABA.

PMID- 14583750
TI  - The acquisitive auditory cortex.

PMID- 14583751
TI  - Understanding the mind's eye...and nose.

PMID- 14583752
TI  - Pulling the Soxs off proliferation.

PMID- 14583753
TI  - The glial identity of neural stem cells.
AB  - Glia are the most numerous cells in the brain, and their many diverse functions
      highlight their essential role in the nervous system. Recent studies have
      revealed an unexpected new role for glia in a wide variety of species, that of
      stem cells/progenitors in the adult and embryonic brain. Differentiation along
      the glial lineage may be a default state of development reflected in the
      progression of stem cells along the neuroepithelial-->radial glia-->astrocyte
      lineage.

PMID- 14583754
TI  - Rapid task-related plasticity of spectrotemporal receptive fields in primary
      auditory cortex.
AB  - We investigated the hypothesis that task performance can rapidly and adaptively
      reshape cortical receptive field properties in accord with specific task demands
      and salient sensory cues. We recorded neuronal responses in the primary auditory
      cortex of behaving ferrets that were trained to detect a target tone of any
      frequency. Cortical plasticity was quantified by measuring focal changes in each
      cell's spectrotemporal response field (STRF) in a series of passive and active
      behavioral conditions. STRF measurements were made simultaneously with task
      performance, providing multiple snapshots of the dynamic STRF during ongoing
      behavior. Attending to a specific target frequency during the detection task
      consistently induced localized facilitative changes in STRF shape, which were
      swift in onset. Such modulatory changes may enhance overall cortical
      responsiveness to the target tone and increase the likelihood of 'capturing' the
      attended target during the detection task. Some receptive field changes persisted
      for hours after the task was over and hence may contribute to long-term sensory
      memory.

PMID- 14583755
TI  - Diagnostic and prognostic prediction using gene expression profiles in high
      dimensional microarray data.
AB  - DNA microarrays are a potentially powerful technology for improving diagnostic
      classification, treatment selection and therapeutics development. There are,
      however, many potential pitfalls in the use of microarrays that result in false
      leads and erroneous conclusions. This paper provides a review of the key features
      to be observed in developing diagnostic and prognostic classification systems
      based on gene expression profiling and some of the pitfalls to be aware of in
      reading reports of microarray-based studies.

PMID- 14583756
TI  - Localised and unresectable neuroblastoma in infants: excellent outcome with low
      dose primary chemotherapy.
AB  - The purpose of this study was to evaluate the efficacy of low-dose chemotherapy
      in infants with localised and unresectable neuroblastoma (NB). All consecutive
      infants with localised NB and no N-myc amplification were eligible in the SFOP
      NBL 94 study. Primary tumour was deemed as unresectable according to imaging data
      showing any risk of immediate resection. Diagnostic procedures and staging were
      conducted according to INSS recommendations. For children, provided that they had
      no threatening symptom (i.e. vital risk or dumb-bell NB with neurologic deficit),
      chemotherapy consisted in low-dose cyclophosphamide (5 mg(-1)kg day(-1) x 5 days)
      and vincristine (0.05 mg kg(-1) at day 1)-CV and repeated one to three times
      every 2 weeks until surgical excision can be safely performed. No postoperative
      treatment was given. Between January 1995 and December 1999, 134 consecutive
      infants with localised NB were registered in the study, of whom 39 had an
      unresectable NB without N-myc amplification. Among them 28 had no threatening
      symptom and received CV according to the protocol. Objective response was
      observed in 14 (50%) and the other 14 were given second-line chemotherapy because
      of no response. Surgery was attempted in 38 patients including 14 after CV alone,
      leading to complete resection in 23. Relapses occurred in four patients all
      local. Survival and event-free survival were 100 and 90+/-5% with a median follow
      up of 55 months (range 33-93). In conclusion primary low-dose chemotherapy
      without anthracyclines is efficient in about half of the infants presenting with
      an unresectable NB and no N-myc amplification, allowing excellent survival rates
      without jeopardising their long-term outcome even for nonresponding patients who
      received standard regimen.

PMID- 14583757
TI  - Extracapsular dissection for clinically benign parotid lumps: reduced morbidity
      without oncological compromise.
AB  - Previous studies have shown that extracapsular dissection (ECD) is an alternative
      approach to superficial parotidectomy (SP) for pleomorphic adenoma parotid
      tumours, associated with low recurrence rates equal to those following SP, but
      with significantly reduced morbidity. However, if a malignant tumour masquerades
      as a clinically benign lump, this approach may be inappropriate. This study
      addressed this question by analysing the outcome of 821 consecutive patients with
      parotid tumours treated at one centre over 40 years and with a median 12 (range 5
      30) years follow-up. Tumours were classified as 'simple' (discrete, mobile, < 4
      cm: n=662) and 'complex' (deep, fixed, facial nerve palsy, > or =4 cm: n=159).
      Among the 'simple' or clinically benign tumours, 503 patients underwent ECD; 159
      patients underwent SP. In all, 32 (5%) clinically benign cases were subsequently
      revealed as malignant histologies (ECD, 12; SP, 20). For each group, 5- and 10
      year cancer-specific survival rates were 100 and 98%, respectively. There were no
      differences in recurrence rates when subanalysed by surgical groups, but ECD was
      associated with significantly reduced morbidity (P < 0.001). This study
      demonstrates that ECD is a viable alternative to superficial parotidectomy for
      the majority of parotid tumours, associated with reduced morbidity without
      oncological compromise.

PMID- 14583758
TI  - Phase I clinical study of a novel lipophilic platinum complex (SM-11355) in
      patients with hepatocellular carcinoma refractory to cisplatin/lipiodol.
AB  - SM-11355 is a platinum complex developed to treat hepatocellular carcinoma (HCC).
      It is administered via the hepatic artery, using a carrier, lipiodol, that
      consists of ethyl esters of iodized poppy seed oil. We have performed a phase I
      clinical trial of an SM-11355-lipiodol formulation in 11 HCC patients, in order
      to investigate the maximum allowable dose and to maximize the efficacy and safety
      of the drug in the treatment of HCC. The SM-11355 arterial infusion suspension
      was administered at doses of 6, 12 and 20 mg ml(-1) in a maximum lipiodol volume
      of 6 ml. An antitumour efficacy rating of complete response was achieved for one
      patient and a partial response rating was achieved for a second patient, giving
      an overall response rate of 18.2%. Anorexia, nausea and vomiting, pyrexia,
      thrombocytopenia and increases in AST, ALT and total bilirubin were observed as
      adverse effects, but each was transient and each patient had recovered completely
      by 4 weeks after drug administration. Hence, we concluded that the maximum
      allowable dose was not reached in this study. Overall, our results suggest that
      SM-11355 is effective in treating HCC and we suggest that the dose for early
      phase II trials should be 20 mg ml(-1).

PMID- 14583759
TI  - Phase II trial of intralesional therapy with interleukin-2 in soft-tissue
      melanoma metastases.
AB  - The objective of the present study was to validate the use of intralesional
      injection of interleukin-2 (IL-2) in patients with skin and soft-tissue melanoma
      metastases. A total of 24 patients with AJCC stage III or IV melanoma and single
      or multiple skin and soft-tissue metastases were included. Interleukin-2
      injections were administered intralesionally into the total number of cutaneous
      and soft-tissue metastases accessible from the skin, 2-3 times weekly, over 1-57
      weeks. Single doses varied from 0.6 to 6 x 10(6) IU, depending on lesion size.
      The clinical response was monitored by sonography and confirmed by
      histopathology; response evaluation was confined to the intralesionally treated
      tumours. Complete response (CR) of the treated metastases was achieved in 15
      patients (62.5%), the longest remission lasting 38 months to date. In five
      patients, partial response (PR) was achieved (21%) and in another three patients,
      progressive disease was observed (one patient not assessable). A total of 245
      metastases were treated with CR in 209 (85%), and PR in 21 (6%). The therapy was
      generally well tolerated; the observed adverse events were mainly of grade 1-2
      severity. Immunohistochemical studies showed the tumour cells undergoing
      apoptosis and revealed a mixed character of the inflammatory infiltrate. The
      unusual high CR rate in metastatic melanoma of 62.5% and the limited toxicity
      suggest that treatment of skin and soft-tissue melanoma metastases with
      intralesional injection of IL-2 may be a safe and effective alternative to
      conventional therapies. The optimal dosage and duration of this therapy still
      remain to be defined in larger prospective multicentre trials.

PMID- 14583760
TI  - The potential for oral combination chemotherapy of 5'-deoxy-5-fluorouridine, a 5
      FU prodrug, and cyclophosphamide for metastatic breast cancer.
AB  - Preclinical studies have demonstrated the synergistic anti-tumour activity of
      combination therapy with the oral cytostatics, 5'-deoxy-5-fluorouridine (5'-DFUR)
      and cyclophosphamide (CPA), in human breast cancer xenograft models. This study
      was performed to evaluate the efficacy and safety of this oral combination
      chemotherapy in the treatment of metastatic breast cancer. In all, 101 patients
      with metastatic breast cancer were enrolled in the study, and the data for 94
      eligible patients of these were evaluated. The patients received twice daily oral
      combinations of 5'-DFUR (1200 mg/body/day) and CPA (100 mg/body/day) for 2 weeks,
      followed by a 1-week rest period. After a median of 19 treatment cycles (range 1
      66 cycles), 16 patients (17.0%) had a complete response, and 40 patients (42.6%)
      had partial responses. The response rate was 59.6% (95% CI, 49.0-69.6%). The
      median time to progression and overall survival times were 11.7 and 40.3 months,
      respectively. The toxicity was mild and tolerable, and the related grade 3/4
      clinical adverse effects consisted of haematological toxicity in 21 patients
      (22%) and nonhaematological toxicity in five patients (5%). These results suggest
      that the oral combination chemotherapy of 5'-DFUR and CPA has low toxicity and is
      a novel, very convenient and effective treatment for metastatic breast cancer.

PMID- 14583762
TI  - Second primary malignancies in thyroid cancer patients.
AB  - The late health effects associated with radioiodine ((131)I) given as treatment
      for thyroid cancer are difficult to assess since the number of thyroid cancer
      patients treated at each centre is limited. The risk of second primary
      malignancies (SPMs) was evaluated in a European cohort of thyroid cancer
      patients. A common database was obtained by pooling the 2-year survivors of the
      three major Swedish, Italian, and French cohorts of papillary and follicular
      thyroid cancer patients. A time-dependent analysis using external comparison was
      performed. The study concerned 6841 thyroid cancer patients, diagnosed during the
      period 1934-1995, at a mean age of 44 years. In all, 17% were treated with
      external radiotherapy and 62% received (131)I. In total, 576 patients were
      diagnosed with a SPM. Compared to the general population of each of the three
      countries, an overall significantly increased risk of SPM of 27% (95% CI: 15-40)
      was seen in the European cohort. An increased risk of both solid tumours and
      leukaemias was found with increasing cumulative activity of (131)I administered,
      with an excess absolute risk of 14.4 solid cancers and of 0.8 leukaemias per GBq
      of (131)I and 10(5) person-years of follow-up. A relationship was found between
      (131)I administration and occurrence of bone and soft tissue, colorectal, and
      salivary gland cancers. These results strongly highlight the necessity to
      delineate the indications of (131)I treatment in thyroid cancer patients in order
      to restrict its use to patients in whom clinical benefits are expected.

PMID- 14583761
TI  - Severe intracellular magnesium and potassium depletion in patients after
      treatment with cisplatin.
AB  - The purpose of this study is (1) to evaluate skeletal muscle magnesium (Mg) and
      potassium (K) during treatment with cisplatin; (2) to evaluate the predictive
      value of plasma (P)-Mg for intracellular Mg during cisplatin treatment; and (3)
      to evaluate whether changes in intracellular K influence skeletal muscle Na,K
      ATPase. In all, 65 patients had a needle muscle biopsy obtained before and 26
      patients both before and after cisplatin treatment. Biopsies were analysed for
      Mg, K, and Na,K-ATPase concentrations, and P-Mg and P-K determined. Treatment
      with a total dose of approximately 500 mg (270 mg m(-2) surface area) cisplatin
      over 80 days was associated with reductions in muscle [Mg] (95% CI) (8.95 (8.23
      9.63) to 7.76 (7.34-8.18) mumol g(-1) wet wt. (P<0.01), and muscle [K] (90.81
      (83.29-98.34) to 82.87 (78.74-87.00) mumol g(-1) wet wt. (P<0.05), as well as in
      P-Mg 0.82 (0.80-0.85) to 0.68 (0.64-0.73) mmol l(-1) (P<0.01 but not in P-K (4.0
      (3.8-4.1) vs 3.8 (3.7-4.0) mmol l(-1)). No simple correlations were observed
      between P-Mg and muscle [Mg], or between P-K and muscle [K], either before (n=65)
      or after (n=26) treatment with cisplatin. The changes in [Mg] and [K] were not
      associated with changes in the muscle Na,K-ATPase concentration. Following
      treatment with cisplatin, an approximately 15% decline in P-Mg was accompanied by
      an approximately 15% loss of muscle [Mg], as well as an approximately 10%
      reduction of muscle [K] and fatigue and muscle weakness previously ascribed to
      hypomagnesaemia may therefore also be well explained by muscle K depletion
      observed despite normal levels of P-K. There was no correlation between P-Mg and
      SM-Mg or between P-K and SM-K. Thus, P-Mg and P-K are not reliable indicators for
      Mg and K depletion during treatment with cisplatin. However, the majority of
      patients will present Mg and K depletion after cisplatin therapy and of these
      only very few patients will present a low P-Mg or P-K. Therefore, routine
      supplementation should be considered in all patients receiving cisplatin.

PMID- 14583763
TI  - Comparison of standard and double reading and computer-aided detection (CAD) of
      interval cancers at prior negative screening mammograms: blind review.
AB  - The study evaluates the role of computer-aided detection (CAD) in improving the
      detection of interval cancers as compared to conventional single (CONV) or double
      reading (DOUBLE). With this purpose, a set of 89 negative cases was seeded with
      31 mammograms reported as negative and developing interval cancer in the
      following 2-year interval (false negative (FN)=11, minimal signs (MS)=20). A
      total of radiologists read the set with CONV and then with CAD. Overall, there
      were 589 cancer and 1691 noncancer readings with both CONV and CAD. Double
      reading was simulated by combining conventional readings in all 171 possible
      combinations of 19 radiologists, resulting in a total of 5301 cancer and 15 219
      noncancer readings. Conventional single, DOUBLE and CAD readings were compared in
      terms of sensitivity and recall rate. Considering all 19 readings, cancer was
      identified in 190 or 248 of 589 readings (32.2 vs 42.1%, chi(2)=11.80, df=1,
      P<0.01) and recalls were 287 or 405 of 1691 readings (16.9 vs 23.9%,
      chi(2)=24.87, df=1, P<0.01) at CONV or CAD, respectively. When considering FN and
      MS cases separately, sensitivity at CONV or CAD was 50.2 or 62.6% (chi(2)=6.98,
      df=1, P=0.01) for FN and 22.3 or 30.7% (chi(2)=6.47, df=1, P=0.01) for MS cases,
      respectively. Computer-aided detection (average of 19 readings) was slightly and
      not significantly less sensitive (sensitivity: 42.1 vs 46.1%, chi(2)=3.24, df=1,
      P=0.07) but more specific (recall rate 23.9 vs 26.1%, chi(2)=3.8, df=1, P=0.04)
      as compared to DOUBLE (average of 171 readings). Average sensitivity for FN cases
      only was 62.6% for CAD and 64.8% for DOUBLE (chi(2)=0.32, df=1, P=0.58).
      Corresponding values for MS cases were 30.7% for CAD and 35.7% for DOUBLE
      (chi(2)=3.53, df=1, P=0.06). Compared to CONV, CAD allowed for improved
      sensitivity, though with reduced specificity, both effects being statistically
      significant. Computer-aided detection was almost as sensitive as DOUBLE but
      significantly more specific. Computer-aided detection might be used in the
      current practice to improve sensitivity of conventional single reading. Based on
      estimates of screening sensitivity and FN/MS interval cancer expected frequency,
      the absolute increase of screening sensitivity expected by introducing CAD
      assisted reading may be estimated around 0.9%. The use of CAD as a possible
      surrogate to conventional DOUBLE needs to be confirmed by further studies, which
      should include a cost-effective analysis.

PMID- 14583764
TI  - Referrals of women with a family history of breast cancer from primary care to
      cancer genetics services in South East Scotland.
AB  - As part of a cluster randomised trial to assess an alternative model of cancer
      genetics services, we gathered data on all referrals from general practitioners
      (GPs) to cancer genetics services in South East Scotland over a 4-year period.
      The referral rate per 1000 patients rose by 48% from 0.21 in the 2-year period
      before the trial to 0.31 during the trial. This increase was much greater in the
      trial group offered the GP clinic service (64% increase compared to a 38%
      increase in those referred to the regional service). Thus, the offer of a more
      local service appeared to have a marked effect on GP management of these women.
      Referral rates to cancer genetics services from general practices varied widely
      with higher referral rates from practices with more female partners. There was a
      negative correlation between referral rates and practice area deprivation scores.
      However, this was not found during the trial in the group which offered clinics
      in general practice, the provision of clinic appointments nearer to the homes of
      more socially deprived women resulting in improved access to women from deprived
      areas. The interaction with the GP appears to be associated with an inappropriate
      level of interest in and expectation of the appropriateness of genetic testing.
      The provision of the clinics within general practice did not result in higher
      levels of confidence among GPs in managing these women.

PMID- 14583765
TI  - Epidemiology of classic Kaposi's sarcoma in the Israeli Jewish population between
      1960 and 1998.
AB  - Trends in the incidence of classic Kaposi's sarcoma in the Jewish population in
      Israel for the period between 1960 and 1998 were analysed. World standardised
      incidence rates of 20.7 and 7.5 per million among men and women, respectively,
      were calculated. The highest incidence rates were displayed by men originated
      from Africa and by Asian-born women.

PMID- 14583766
TI  - Risk factors for breast cancer in young women by oestrogen receptor and
      progesterone receptor status.
AB  - We used data from 765 cases and 564 controls in the population-based Australian
      Breast Cancer Family Study to investigate whether, in women under the age of 40,
      the profile of risk factors differed between breast cancer subtypes defined by
      joint oestrogen and progesterone receptor status. As hypothesised, no significant
      differences were found.

PMID- 14583767
TI  - Preterm birth, birth weight, and subsequent risk of female breast cancer.
AB  - We have previously found an increased risk of breast cancer among women born
      preterm. To confirm or refute the results, an enlarged study was conducted. The
      results from this study do not confirm the initial findings and suggest that
      preterm birth can be ruled out as a risk factor for breast cancer.

PMID- 14583768
TI  - Lifetime body mass index and risk of oral cavity and oropharyngeal cancer by
      smoking and drinking habits.
AB  - The influence of body mass index (BMI) on oral cancer risk was evaluated in 375
      incident cases and 375 age-gender-matched hospital-based controls. Low BMIs at
      diagnosis and 2 years before diagnosis were associated with significantly
      elevated odds ratios (OR for BMI < or =22 vs >26 kg m(-2); 3.64; 95% confidence
      interval, CI: 2.27-5.82 and 3.31; 95% CI: 2.04-5.39, respectively). The
      association with low BMI, however, tended to be weaker and nonsignificant among
      never smokers and never drinkers.

PMID- 14583769
TI  - Dietary fat and breast cancer risk revisited: a meta-analysis of the published
      literature.
AB  - Animal experiments and human ecological studies suggest that dietary fat intake
      is associated with a risk of breast cancer, but individual-based studies have
      given contradictory results. We have carried out a meta-analysis of this
      association to include all papers published up to July 2003. Case-control and
      cohort studies that examined the association of dietary fat, or fat-containing
      foods, with risk of breast cancer were identified. A total of 45 risk estimates
      for total fat intake were obtained. Descriptive data from each study were
      extracted with an estimate of relative risk and its associated 95% confidence
      interval (CI), and were analysed using the random effects model of DerSimonian
      and Laird. The summary relative risk, comparing the highest and lowest levels of
      intake of total fat, was 1.13 (95% CI: 1.03-1.25). Cohort studies (N=14) had a
      summary relative risk of 1.11 (95% CI: 0.99-1.25) and case-control studies (N=31)
      had a relative risk of 1.14 (95% CI 0.99-1.32). Significant summary relative
      risks were also found for saturated fat (RR, 1.19; 95% CI: 1.06-1.35) and meat
      intake (RR, 1.17; 95% CI 1.06-1.29). Combined estimates of risk for total and
      saturated fat intake, and for meat intake, all indicate an association between
      higher intakes and an increased risk of breast cancer. Case-control and cohort
      studies gave similar results.

PMID- 14583770
TI  - Opposing effects of dietary n-3 and n-6 fatty acids on mammary carcinogenesis:
      The Singapore Chinese Health Study.
AB  - We investigated the effects of individual fatty acids on breast cancer in a
      prospective study of 35,298 Singapore Chinese women aged 45-74 years, who were
      enrolled during April 1993 to December 1998 (The Singapore Chinese Health Study).
      At recruitment, each study subject was administered, in-person, a validated,
      semiquantitative food frequency questionnaire consisting of 165 food and beverage
      items. As of December 31, 2000, 314 incident cases of breast cancer had occurred.
      We used the Cox regression methods to examine individual fatty acids in relation
      to breast cancer risk, with adjustment for age at baseline interview, year of
      interview, dialect group, level of education, daily alcohol drinking, number of
      live births, age when menstrual periods became regular, and family history of
      breast cancer. Consumption of saturated, monounsaturated or polyunsaturated fat
      overall was unrelated to risk. On the other hand, high levels of dietary n-3
      fatty acids from fish/shellfish (marine n-3 fatty acids) were significantly
      associated with reduced risk. Relative to the lowest quartile of intake,
      individuals in the higher three quartiles exhibited a 26% reduction in risk
      (relative risk (RR)=0.74, 95% confidence interval (CI)=0.58, 0.94)); RRs were
      similar across the top three quartiles of intake (0.75, 0.75, 0.72,
      respectively). Overall, there was no association between n-6 fatty acids and
      breast cancer risk. However, among subjects who consumed low levels of marine n-3
      fatty acids (lowest quartile of intake), a statistically significant increase in
      risk was observed in individuals belonging to the highest vs the lowest quartile
      of n-6 fatty acid consumption (RR=1.87, 95% CI=1.06-3.27); the corresponding RR
      for advanced breast cancer was 2.45 (95% CI=1.20-4.97, P for trend=0.01). To our
      knowledge, these are the first prospective findings linking the intake of marine
      n-3 fatty acids to breast cancer protection.

PMID- 14583771
TI  - Socioeconomic effects on breast cancer survival: proportion attributable to stage
      and morphology.
AB  - Breast cancer patients of lower socioeconomic status tend to have poorer
      survival. Among 10 865 cases of breast cancer from the East Anglian Cancer
      Registry diagnosed between 1982 and 1993, we estimated the extent to which the
      differences in survival by socioeconomic status, measured by both occupational
      and area-based methods, can be explained by differences between socioeconomic
      groups in stage and morphological type of tumour. In univariate survival
      analyses, lower social class (manual occupation) was associated with a relative
      hazard of 1.32 (95% CI 1.12-1.55) for death from breast cancer as underlying
      cause. Women resident in the most deprived area had a relative hazard of 1.21
      (0.95-1.54) for death from breast cancer as underlying cause. Stage of disease
      accounted for 28% of the effect of social class on survival but for none of the
      effect of deprivation category. Morphological type accounted for 3% of the effect
      of social class and none of the effect of deprivation category. Thus, stage at
      presentation explains some but not all of the socioeconomic differences in breast
      cancer survival. Future research on histological grade and socioeconomic status
      is indicated.

PMID- 14583772
TI  - Serum levels of insulin-like growth factor-I, IGF-binding protein 1 and 3, and
      insulin and endometrial cancer risk.
AB  - Insulin-like growth factor-I (IGF-I) and IGF-binding protein-1 and 3 (IGFPB-1,
      IGFPB-3) are expressed in normal and neoplastic endometrium. Their role and the
      role of insulin in the aetiology of endometrial cancer, is unclear. We performed
      a population-based case-control study in Sweden, including 288 endometrial cancer
      patients and 392 control women and analysed total serum IGF-I, IGFBP-1, IGFBP-3,
      insulin and BMI levels stratified by disease and hormone replacement therapy
      status (HRT). Non-parametric statistical tests and logistic regression analyses
      were performed to assess associations with endometrial cancer. There were no
      substantial differences between the mean serum levels of IGF-I between cases
      (115.5, s.d. 61.3) and controls (110.6; s.d. 50.4; Wilcoxon P=0.84), or between
      subgroups of women classified according to other risk factors for endometrial
      cancer. There were no trends of increasing risk according to quartiles of IGF-I,
      IGFBP-1, IGFBP-3 and insulin serum levels. There was an increasing risk of
      endometrial cancer according to the serum levels of IGFBP-1, which was observed
      only among women who had ever used HRT. Serum IGF-I, IGFBP-1, IGFBP-3 and insulin
      levels seem unrelated to endometrial cancer risk. Among users of HRT, increasing
      IGFBP-1 levels seem to increase endometrial cancer risk.

PMID- 14583773
TI  - Aspirin use and lung cancer in men.
AB  - We examined prospectively the relation between regular aspirin use and lung
      cancer risk in the Health Professionals Follow-Up Study. Of 49,383 US men aged 40
      75 years who completed biennial self-administered questionnaires that assessed
      aspirin use beginning in 1986, 328 developed lung cancer during 601,453 person
      years of follow-up through 31 December 2000. No information on aspirin dose was
      available. Controlling for current age, smoking status, and age at starting to
      smoke regularly, the relative risk (RR) of total lung cancer for regular users of
      aspirin (twice or more per week) at baseline compared to nonusers was 1.13 (95%
      confidence interval (CI) =0.89-1.43). Results were similar for non-small-cell
      lung cancer (RR=1.16; 95% CI=0.88-1.54). No apparent dose-dependent association
      was observed for the frequency of aspirin use and lung cancer risk (P for
      trend=0.64), and results remained null when consistent use of aspirin over time
      was examined. These findings do not suggest that regular aspirin use is
      associated with a reduced lung cancer risk.

PMID- 14583774
TI  - Cancer incidence in children and young adults did not increase relative to
      parental exposure to atomic bombs.
AB  - We have examined whether parental exposure to atomic bomb radiation has led to
      increased cancer risks among the offspring. We studied 40,487 subjects born from
      May 1946 through December 1984 who were cancer-free in January 1958. One or both
      parents were in Hiroshima or Nagasaki at the time of the bombing and for
      childbirth. Using population-based tumor registry data we analyzed cancer
      incidence data from 1958 to 1997 by Cox regression models, and we examined the
      effects of both paternal and maternal irradiation with adjustment for city, sex,
      birth year, and migration. During follow-up, 575 solid tumor cases and 68
      hematopoietic tumor cases were diagnosed. Median age at diagnosis was 39.7 years.
      Median doses were 143 millisierverts for 15,992 exposed (5+ millisierverts or
      unknown dose) fathers and 133 millisierverts for 10,066 exposed mothers. Cancer
      incidence was no higher for subjects with exposed parents than for the reference
      subjects (0-4 millisierverts), nor did the incidence rates increase with
      increasing dose. For 3568 subjects with two exposed parents, the adjusted risk
      ratio for all cancer was 0.97 (95% confidence interval 0.70-1.36). Because of the
      small number of cases, however, we cannot exclude an increase in cancer incidence
      at this time.

PMID- 14583775
TI  - Multiple and synergistic deregulations of apoptosis-controlling genes in
      pancreatic carcinoma cells.
AB  - Inability to die by apoptosis is one of the reasons for the deregulated growth of
      tumour cells and the frequently observed failure of chemotherapy. In this study
      we thought to identify the common and functionally important characteristics
      responsible for the apoptosis resistance of pancreatic tumour cells. We analysed
      cell surface expression level of death receptors CD95 and TRAIL-R1-4 as well as
      the expression profile of sixteen apoptosis-relevant proteins in five pancreatic
      carcinoma cell lines Capan1, Colo357, PancTuI, Panc89 and Panc1. These data were
      evaluated in the context of sensitivity towards anti-CD95 and TRAIL-mediated
      apoptosis. Here we report that except for resistant Panc1 cells, which only
      marginally expressed CD95, all other cell lines showed comparable levels of CD95
      and TRAIL receptors irrespectively of their apoptotic phenotype. Interestingly,
      we found that the elevated expression of FLIP, Bcl-x(L) and IAP in parallel with
      a downregulation of FADD and Bid was common for the resistant cell lines.
      Consequently, stable overexpression of XIAP, Bcl-x(L) or dominant negative FADD
      in sensitive cells significantly reduced the death receptor mediated apoptosis
      while the overexpression of Bid rendered the resistant cells sensitive.

PMID- 14583776
TI  - Follow-up of collagen crosslink excretion in patients with oral squamous cell
      carcinoma and analysis of tissue samples.
AB  - The presence of an oral squamous cell carcinoma (OSCC) may be associated with
      increased urinary excretion of the markers of collagen degradation,
      hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP). We investigated the
      possibility of these markers predicting the presence of active disease. Patients
      from a current study on HP and LP were included as follows: Group 1a (OSCC with
      confirmed mandibular bony infiltration, n=12), group 1b (group 1a patients >6
      months after successful treatment), group 2a (OSCC without evidence of mandibular
      bone infiltration, n=8), group 2b (group 2a patients >6 months after successful
      treatment), group 3a (recurrent OSCC, n=8), group 3b (group 3a patients >6 weeks
      later, symptoms unchanged) and group 4 (control group, n=74). Tissue samples from
      tumour tissue and adjacent healthy mucosa were additionally investigated for HP
      and LP concentrations (n=8). The decrease in the urinary concentrations of HP and
      LP was statistically significant between groups 1a and 1b (P<0.001 for HP and
      LP), but not between groups 2a and 2b (P=0.07 for HP and LP), while values in
      groups 1b and 2b were within the normal range. When comparing groups 3a and 3b, a
      significant increase was observed for LP (P=0.050), but not HP (P=0.208). In
      conclusion, successful treatment of OSCC with bony involvement may be associated
      with a reduction of urinary HP and LP, whereas ongoing disease may result in an
      increase of LP. HP and LP may both be useful markers of tumour progression in
      patients with OSCC.

PMID- 14583777
TI  - Characterisation of p53 status at the gene, chromosomal and protein levels in
      oesophageal adenocarcinoma.
AB  - p53 mutations and loss of heterozygosity have been commonly associated with
      oesophageal adenocarcinoma. In this investigation, the p53 status of a Welsh
      population of Barrett's-associated oesophageal adenocarcinomas were fully
      characterised at the gene sequence, chromosomal, mRNA and protein levels. In
      total, 31 tumours were examined for p53 gene sequence mutations using RFLP with
      sequencing, allelic loss of the gene was characterised by FISH, mRNA expression
      by p53 pathway signalling arrays and protein levels by p53 immunohistochemistry.
      In all, 9.6% of adenocarcinomas harboured p53 mutations, 24% displayed p53
      allelic loss and 83% exhibited p53 protein accumulation. Point mutations and
      deletions of the gene did not coexist within the same samples. All samples
      containing p53 mutations also displayed positive immunostaining; however; in the
      majority of cases, p53 protein accumulation developed in the absence of
      mutations. The gene expression analysis demonstrated no differences in p53 and
      mdm-2 transcription levels between the p53 immunonegative and immunopositive
      samples, indicating other mechanisms underlie the proteins' overexpression. In
      conclusion, p53 mutations and deletions do not appear to be frequent events in
      oesophageal adenocarcinomas; however, abnormal accumulation of the protein is
      present in a vast majority of cases. P53 gene mutations are not the primary cause
      of protein overexpression--an alternative mechanism is responsible for the
      positive p53 immunohistochemistry detected.

PMID- 14583778
TI  - Clinical significance of immune cell infiltration within gallbladder cancer.
AB  - To investigate the pathophysiological significance of infiltrating antitumour
      immune cells, we evaluated the quantity of immune cell intratumoral infiltration
      in 110 surgically resected gallbladder specimens by immunohistochemistry. We
      examined 45 cases of gallbladder cancer and 65 cases of benign gallbladder
      diseases for CD4(+) T cells, CD8(+) T cells, natural killer cells (NKCs), and
      dendritic cells (DCs). High levels of CD4(+) T cell, CD8(+) T cell, NKC, and DC
      infiltration were recognised in 51.1% (23 out of 45), 37.8% (17 out of 45), 33.3%
      (15 out of 45), and 48.9% (22 out of 45) of cancer specimens, respectively. High
      numbers of infiltrating CD4(+) and CD8(+) T cells correlated with decreasing
      tumour invasion, and high numbers of infiltrating DCs correlated with decreasing
      lymph-node tumour metastasis. Furthermore, increased infiltration of CD4(+) and
      CD8(+) T cells and DCs exhibited a significant correlation with prolonged
      survival. NKC infiltration, however, did not correlate with any of the
      clinicopathological factors examined. Additionally, high levels of infiltration
      were not identified in specimens from benign diseases, consistent with the cancer
      specific activity of CD4(+) and CD8(+) T cells and DCs. In this study, we
      demonstrate that CD4(+) and CD8(+) tumour-infiltrating lymphocyte and DCs, but
      not NKCs, are important factors in the accurate prognosis of survival after
      surgical removal of gallbladder adenocarcinoma.

PMID- 14583779
TI  - Nuclear expression of Survivin in paediatric ependymomas and choroid plexus
      tumours correlates with morphologic tumour grade.
AB  - Survivin is a gene that is widely expressed throughout the development of the
      normal mammalian embryo. Subcellular localisation of Survivin to both the nucleus
      and cytoplasm has suggested multiple functional roles, including inhibition of
      cell death, especially as demonstrated within a variety of malignant cell types,
      as well as regulation of the mitotic spindle checkpoint. The expression of
      Survivin has been associated with an adverse clinical outcome in a large number
      of malignancies. However, nuclear Survivin expression has been described as an
      independent variable of favourable prognosis in two large clinical studies of
      breast and gastric carcinomas. Reports of Survivin expression in normal
      postnatal, differentiated tissues have been restricted to cell types with high
      proliferative capacities, including vascular endothelium, endometrium, colonic
      epithelium, and activated lymphocytes. Prior to this report, expression within
      the normal human brain had not been characterised. Here, we analyse the
      expression of Survivin in human brain sections obtained from perinatal and
      paediatric autopsy cases. We report a strikingly high level of expression of
      Survivin within normal ependyma and choroid plexus (CP). Analysis of
      corresponding neoplastic tissue in paediatric ependymomas and CP tumours shows
      that expression of the nuclear form of Survivin correlates with morphologic
      tumour grade, with a loss of nuclear expression associated with progressive
      cytologic anaplasia. This pattern of expression supports a hypothesis that
      Survivin plays a functional role in normal ependymal growth and/or neural stem
      cell differentiation, and that abnormally low levels of expression of the nuclear
      form of this protein may be a marker of more aggressive disease and/or higher
      morphologic grade in ependymal and CP tumours.

PMID- 14583780
TI  - Quantitative evaluation of metastases in axillary lymph nodes of breast cancer.
AB  - We have established a highly sensitive and quantitative reverse transcriptase
      polymerase chain reaction (RT-PCR) method to detect axillary lymph node
      metastases of breast cancer. Amplifying cytokeratin 19 (CK19) mRNA transcripts
      using real-time TaqMan PCR made it possible to quantify axillary metastatic
      burden. Metastases in 358 axillary lymph nodes obtained from 23 breast cancers of
      22 patients were investigated by conventional haematoxylin and eosin (H&E)
      staining, immunohistochemical staining and quantitative RT-PCR assay. The
      detection rates of axillary lymph node metastasis using H&E staining,
      immunohistochemistry and RT-PCR assay were 4.5, 5.9 and 13.1%, respectively. RT
      PCR assay was the most sensitive of these three methods for detecting lymph node
      metastases. Cytokeratin 19 mRNA expression values of both histologically and
      immunohistochemically positive lymph nodes were significantly higher than the
      values for lymph nodes judged to be negative by both histological and
      immunohistochemical methods (P<0.0001), and those of histologically negative, but
      immunohistochemically positive lymph nodes were significantly higher than the
      values for lymph nodes judged to be negative by both histological and
      immunohistochemical methods (P<0.0001). Furthermore, metastatic rates of sentinel
      nodes were higher than the rates of nonsentinel lymph nodes as measured by all
      three methods. These results indicate that quantitative RT-PCR assay is a
      sensitive and reliable method for detecting lymph node metastasis. Furthermore,
      quantification of metastases in sentinel lymph nodes by quantitative RT-PCR assay
      may be useful to assess the entire axillary burden of breast cancer patients.

PMID- 14583781
TI  - c-Myc overexpression sensitises colon cancer cells to camptothecin-induced
      apoptosis.
AB  - The proto-oncogene c-Myc is overexpressed in 70% of colorectal tumours and can
      modulate proliferation and apoptosis after cytotoxic insult. Using an isogenic
      cell system, we demonstrate that c-Myc overexpression in colon carcinoma LoVo
      cells resulted in sensitisation to camptothecin-induced apoptosis, thus
      identifying c-Myc as a potential marker predicting response of colorectal tumour
      cells to camptothecin. Both camptothecin exposure and c-Myc overexpression in
      LoVo cells resulted in elevation of p53 protein levels, suggesting a role of p53
      in the c-Myc-imposed sensitisation to the apoptotic effects of camptothecin. This
      was confirmed by the ability of PFT-alpha, a specific inhibitor of p53, to
      attenuate camptothecin-induced apoptosis. p53 can induce the expression of
      p21(Waf1/Cip1), an antiproliferative protein that can facilitate DNA repair and
      drug resistance. Importantly, although camptothecin treatment markedly increased
      p21(Waf1/Cip1) levels in parental LoVo cells, this effect was abrogated in c-Myc
      overexpressing derivatives. Targeted inactivation of p21(Waf1/Cip1) in HCT116
      colon cancer cells resulted in significantly increased levels of apoptosis
      following treatment with camptothecin, demonstrating the importance of
      p21(Waf1/Cip1) in the response to this agent. Finally, cDNA microarray analysis
      was used to identify genes that are modulated in expression by c-Myc upregulation
      that could serve as additional markers predicting response to camptothecin.
      Thirty-four sequences were altered in expression over four-fold in two isogenic c
      Myc-overexpressing clones compared to parental LoVo cells. Moreover, the
      expression of 10 of these genes was confirmed to be significantly correlated with
      response to camptothecin in a panel of 30 colorectal cancer cell lines.

PMID- 14583783
TI  - P-glycoprotein and Mrp1 collectively protect the bone marrow from vincristine
      induced toxicity in vivo.
AB  - ABC transporter proteins may protect haematopoietic progenitor cells from
      chemotherapy-induced toxicity. By using an in vitro colony-forming assay, we
      found that bone marrow of Mdr1ab, Mrp1, Mdr1ab/Mrp1 knockout (KO) mice was two-,
      five- to 10- and 25-fold, respectively, more sensitive to vincristine than wild
      type mice bone marrow. To study the impact of ABC transporters on in vivo bone
      marrow sensitivity without the added complication of altered pharmacokinetics, we
      created chimeras of wild-type mice transplanted with bone marrow from wild-type,
      Mrp1, Mdr1ab or Mdr1ab/Mrp1 KO donor mice. Following a single bolus injection of
      vincristine, the chimeras transplanted with wild-type or Mdr1ab KO marrow cells
      showed no reductions in WBC. A significant reduction was observed in Mrp1 KO
      chimeras, but the most pronounced effect was observed in mice receiving bone
      marrow from Mdr1ab/Mrp1 KO mice. A pharmacokinetic analysis in wild-type and KO
      mice showed that the absence of P-gp reduced the body clearance of vincristine,
      but that no further reduction occurred when Mrp1 was also absent. However, the
      tissue accumulation of vincristine in tissues of these Mdr1ab/Mrp1 KO mice was
      further increased. This study demonstrates that the presence of multiple drug
      transporters protects the bone marrow, and probably other tissues as well,
      against chemotherapeutic insults.

PMID- 14583782
TI  - A novel approach in the treatment of neuroendocrine gastrointestinal tumours.
      Targeting the epidermal growth factor receptor by gefitinib (ZD1839).
AB  - Therapeutic options to inhibit the growth and spread of neuroendocrine (NE)
      gastrointestinal tumours are still limited. Since gefitinib (4-(3-chloro-4
      fluoroanilino)-7-methoxy-6-(3-morpholinopropoxy)quinazoline), an inhibitor of
      epidermal growth factor receptor-sensitive tyrosine kinase (EGFR-TK), had been
      shown to suppress potently the growth of various non-NE tumour entities, we
      studied the antineoplastic potency of gefitinib in NE gastrointestinal tumour
      cells. In human insulinoma (CM) cells, in human pancreatic carcinoid (BON) cells
      and in NE tumour cells of the gut (STC-1), gefitinib induced a time- and dose
      dependent growth inhibition by almost 100%. The antiproliferative potency of
      gefitinib correlated with the proliferation rate of the tumour cells. So the
      IC(50) value of gefitinib was 4.7+/-0.6 microM in the fast-growing CM cells,
      still 16.8+/-0.4 microM in the moderate-growing BON cells, and up to 31.5+/-2.5
      microM in the slow-growing STC-1 cells. Similarly, the induction of apoptosis and
      cell-cycle arrest by gefitinib differed according to growth characteristics: fast
      growing CM cells displayed a strong G0/G1 arrest in response to gefitinib, while
      no significant cell-cycle alterations were seen in the slow-growing STC-1. Vice
      versa, the proapoptotic effects of gefitinib, as determined by caspase-3
      activation and DNA fragmentation, were most pronounced in the slow-growing STC-1
      cells. Using cDNA microarrays, we found extensive changes in the expression of
      genes involved in the regulation of apoptosis and cell cycle after incubation
      with gefitinib. Among them, an upregulation of the growth arrest and DNA damage
      inducible gene GADD153 was observed. Phosphorylation of ERK1/2, which inhibits
      GADD153 expression, was reduced in a time-dependent manner. However, no gefitinib
      induced activation of the GADD153-inducing p38 mitogen-activated protein kinase
      was detected. Our data demonstrate that the inhibition of EGFR-TK by gefitinib
      induces growth inhibition, apoptosis and cell-cycle arrest in NE gastrointestinal
      tumour cells. Thus, EGFR-TK inhibition appears to be a promising novel approach
      for the treatment of NE tumour disease.

PMID- 14583784
TI  - Signal transduction pathways involved in proteolysis-inducing factor induced
      proteasome expression in murine myotubes.
AB  - The proteolysis-inducing factor (PIF) is produced by cachexia-inducing tumours
      and initiates protein catabolism in skeletal muscle. The potential signalling
      pathways linking the release of arachidonic acid (AA) from membrane phospholipids
      with increased expression of the ubiquitin-proteasome proteolytic pathway by PIF
      has been studied using C(2)C(12) murine myotubes as a surrogate model of skeletal
      muscle. The induction of proteasome activity and protein degradation by PIF was
      blocked by quinacrine, a nonspecific phospholipase A(2) (PLA(2)) inhibitor and
      trifluroacetyl AA, an inhibitor of cytosolic PLA(2). PIF was shown to increase
      the expression of calcium-independent cytosolic PLA(2), determined by Western
      blotting, at the same concentrations as those inducing maximal expression of 20S
      proteasome alpha-subunits and protein degradation. In addition, both U-73122,
      which inhibits agonist-induced phospholipase C (PLC) activation and D609, a
      specific inhibitor of phosphatidylcholine-specific PLC also inhibited PIF-induced
      proteasome activity. This suggests that both PLA(2) and PLC are involved in the
      release of AA in response to PIF, and that this is important in the induction of
      proteasome expression. The two tyrosine kinase inhibitors genistein and
      tryphostin A23 also attenuated PIF-induced proteasome expression, implicating
      tyrosine kinase in this process. PIF induced phosphorylation of p44/42 mitogen
      activated protein kinase (MAPK) at the same concentrations as that inducing
      proteasome expression, and the effect was blocked by PD98059, an inhibitor of
      MAPK kinase, as was also the induction of proteasome expression, suggesting a
      role for MAPK activation in PIF-induced proteasome expression.

PMID- 14583785
TI  - Ex vivo analysis of topotecan: advancing the application of laboratory-based
      clinical therapeutics.
AB  - Topotecan is currently approved for relapsed small-cell lung cancer and ovarian
      cancer. Topotecan's efficacy in the second-line setting and novel mechanism of
      action suggest broad antitumour activity. We utilised a clinically validated,
      cell-death, ex vivo assay in human tumour explants to examine the activity
      profile of topotecan alone and in combination with other antitumour agents.
      Serial dilutions of topotecan alone and in combination with other cytotoxic
      agents were applied to biopsy specimens of non-small-cell lung cancer (NSCLC) and
      breast, colon, and prostate cancers. Dose-response curves were interpolated to
      provide 50% lethal concentrations (LC(50)). The degree of synergy (by median
      effect) and normalised Z-scores (raw scores converted to relative activity
      distributed around the mean) were then computed. Single-agent activity was
      observed for topotecan in all four tumour types. In 57 chemotherapy-naive
      specimens, NSCLC revealed the highest activity, demonstrated by the lowest LC(50)
      value (0.26+/-0.06 microg ml(-1); P=0.002). Overall, previously treated and
      chemotherapy-naive specimens revealed no significant differences in mean
      LC(50)'s. Synergy was observed for several combinations, including topotecan plus
      cisplatin in prostate and for topotecan plus 5-fluorouracil in breast cancers.
      The Z-score analyses conducted suggest activity for previously unexplored drug
      regimens, including topotecan plus 5-fluorouracil, vinorelbine, and mitomycin-C
      in NSCLC and breast cancer. Phase II studies are underway to determine the degree
      to which these ex vivo findings will translate into improved clinical results.

PMID- 14583786
TI  - Non-invasive 19F MR spectroscopy of 5-fluorocytosine to 5-fluorouracil conversion
      by recombinant Salmonella in tumours.
AB  - The aim of this study was to evaluate the applicability of fluorine-19 magnetic
      resonance spectroscopy ((19)F MRS) for monitoring in vivo the conversion of 5
      fluorocytosine (5-FC) to 5-fluorouracil (5-FU) after using an attenuated
      Salmonella Typhimurium strain recombinant to provide cytosine deaminase (TAPET
      CD). The (19)F MRS measurements were done on mice bearing the human colon tumour
      xenograft (HCT116). The intratumoural conversion is greater when TAPET-CD/5-FC is
      delivered intratumourally (i.tu.) than when TAPET-CD is delivered intravenously
      (i.v.) and 5-FC intraperitoneally (i.p.). Repeat measurements of the same tumour
      also yielded important information on the tumour colonization by TAPET-CD through
      the correlated 5-FC to 5-FU conversion efficacy. The in vivo MRS spectra were
      confirmed by in vitro (19)F MRS of perchloric acid extracts of the tumour tissue.
      No 5-FU metabolites were detectable in vivo in the tumours. However, the in vitro
      measurements revealed, besides 5-FC and 5-FU, the presence of small amounts of
      catabolites. Finally, spectra obtained in vitro from liver extracts of tumour
      bearing mice treated i.tu. with TAPET-CD/5-FC showed no 5-FU and only little
      amounts of catabolites. Our data illustrate most importantly the potential of
      (19)F MRS to monitor biologically-based treatments involving cytosine deaminase.

PMID- 14583787
TI  - p16 Gene transfer increases cell killing with abnormal nucleation after ionising
      radiation in glioma cells.
AB  - It is well established that cells synchronised at the G1-S phase are highly
      radiosensitive. In this study, p16-null human glioma cell lines were induced into
      G1 cell cycle arrest by adenovirus-mediated p16 gene transfer, and examined for
      radiation-induced cell killing. Clonogenic analysis and trypan blue extraction
      test showed that the p16 gene transfer enhanced radiation-induced cell killing in
      p16-null glioma cell lines. TUNEL assays and pulse-field gel electrophoresis
      confirmed that the radiation-induced cell killing of p16-transfected cells could
      be caused by a nonapoptotic mechanism. Gimsa staining demonstrated that
      irradiation alone or Ax-mock infection plus irradiation results in a slight
      increase in the frequency of cells with abnormal nucleus, compared to
      unirradiated uninfected or Ax-mock infected cells. However, Ax-hp16 or Ax-hp21
      infection alone modestly increased the frequency of cells with abnormal nucleus
      (especially bi- and multinucleation), and 4-Gy irradiation of Ax-hp16 or Ax-hp21
      infected cells substantially enhanced this frequency. These results suggest that
      there exists some unknown interaction between radiation and p16 in
      cytoplasm/membranes, which decreases cytokinesis and promotes abnormal
      nucleation. Thus, p16 expression prevented radiation-induced apoptosis by
      promoting abnormal nucleation, thereby leading to another mode of cell death.

PMID- 14583788
TI  - TIMP-1 enhancer sequence--real or bacterial?

PMID- 14583790
TI  - Prostate cancer, insulin, and androgen deprivation therapy.

PMID- 14583793
TI  - Multiple mechanisms of estrogen receptor gene repression contribute to ER
      negative breast cancer.

PMID- 14583794
TI  - HLA and HIV: modeling adaptation to moving targets.

PMID- 14583795
TI  - Pharmacogenomic approaches to osteoporosis.

PMID- 14583796
TI  - Pharmacological treatment of monogenic disease.

PMID- 14583797
TI  - Association of dopaminergic and serotonergic genes with tardive dyskinesia in
      patients with chronic schizophrenia.
AB  - Tardive dyskinesia (TD) is a long-term adverse effect of antipsychotic drugs that
      are dopamine D2 receptor blockers. Serotonin receptor antagonism has been
      proposed as a common mechanism contributing to the low extrapyramidal side effect
      profile of atypical antipsychotic drugs. We evaluated candidate dopamine and
      serotonin genes for association with drug-induced TD. We examined three
      polymorphisms in the dopamine D2 receptor gene (DRD2), two sites in the 3' region
      of the dopamine transporter (DAT) gene, two sites in the promoter and coding
      region of the dopamine D4 (DRD4) receptor gene, as well as polymorphic sites in
      the serotonin 6 receptor gene, the serotonin transporter gene and the tryptophan
      hydroxylase gene, for association with TD susceptibility. Schizophrenic patients
      with (n=59) and without TD (n=63), matched for antipsychotic drug exposure and
      other relevant variables, were studied. No significant associations were found.
      Within the limitations imposed by the size of the clinical sample, these findings
      suggest that the above polymorphic loci do not contribute significantly to risk
      for TD. Further examination of loci that yielded positive results at a trend
      level and investigation of other candidate genetic loci coding for antipsychotic
      drug targets is warranted.

PMID- 14583798
TI  - Haplotypes of the cholesteryl ester transfer protein gene predict lipid-modifying
      response to statin therapy.
AB  - Cholesteryl ester transfer protein (CETP) plays a central role in high-density
      lipoprotein (HDL) metabolism. Single nucleotide polymorphisms (SNPs) and
      haplotypes in the CETP gene were determined in 98 patients with untreated
      dyslipidemias and analyzed for associations with plasma CETP and plasma lipids
      before and during statin treatment. Individual CETP SNPs and haplotypes were both
      significantly associated with CETP enzyme mass and activity. However, only
      certain CETP haplotypes, but not individual SNPs, significantly predicted the
      magnitude of change in HDL cholesterol (HDL-C) and triglycerides. After adjusting
      for covariates and multiple testing, the TTCAAA haplotype showed a gene-dose
      effect in predicting the HDL-C increase (P=0.03), while the TTCAAAGGG and AAAGGG
      haplotypes predicted a decrease in triglycerides (P=0.04 both). This is the first
      study to demonstrate that SNP haplotypes derived from allelic SNP combinations in
      the CETP gene were more informative than single SNPs in predicting the response
      to lipid-modifying therapy with statins.

PMID- 14583799
TI  - Investigation of polymorphism in the MDR1 gene and antidepressant-induced mania.
AB  - The involvement of the multi-drug-resistant 1 P-glycoprotein gene (MDR1 P-gp) in
      the transport of antidepressants across the blood-brain barrier makes it a good
      candidate for the prediction of antidepressant response and side effects. We
      investigated the role of the MDR1 P-gp gene in predicting the induction of mania
      in bipolar patients (BP) treated with proserotonergic drugs. Participants met the
      DSM-IV criteria for BP or BPII and had at least one depressive episode treated
      with proserotonergic antidepressants. The first group (n=26) included patients
      with at least one DSM-IV manic/hypomanic episode developed during antidepressant
      treatment; the second group (N=29) included patients with no antidepressant
      induced switches. The common polymorphism of the MDR1 was genotyped for both
      groups and comparison was made with respect to the presence/absence of induced
      mania between the two groups. No association between antidepressant-induced mania
      and the MDR1 alleles or genotypes was found (chi2=1.85, 2 df, P=0.39; chi2=0.13,
      1 df, P=0.72).

PMID- 14583800
TI  - CYP2C9 gene and susceptibility to major depressive disorder.
AB  - Alteration of monoaminergic neurotransmission has been implicated in the
      pathophysiology of mood disorders, and CYP2C9 enzyme activity has been shown to
      be modulated by serotonin in vitro. The present study was aimed at analysing the
      frequency of CYP2C9 alleles (*1, *2, *3) among patients suffering from major
      depressive disorder. In all, 70 such suffering psychiatric outpatients were
      studied. The CYP2C9 genotypes were determined by allele-specific PCR. The
      CYP2C9*3 allele frequency was higher (P<0.01) among the patients suffering from
      major depression than in a population of 89 schizophrenic patients (odds
      ratio=3.3) and 138 healthy volunteers (odds ratio=2.8). The results suggest that
      CYP2C9 genetic polymorphism may be related to a major depressive disorder due to
      an alteration in endogenous metabolism, although a linkage between CYP2C9 and
      some other gene related to depression cannot be ruled out.

PMID- 14583801
TI  - Maori/non-Maori alcohol consumption profiles: implications for reducing health
      inequalities.

PMID- 14583802
TI  - Improving quality: maintaining the momentum.

PMID- 14583803
TI  - Differences in patterns of alcohol consumption between Maori and non-Maori in
      Aotearoa (New Zealand).
AB  - AIM: To describe relative differences in alcohol consumption patterns in Maori
      and non-Maori from all available large-scale New Zealand surveys. METHODS: Data
      from five New Zealand surveys (national and population specific) conducted since
      1988 were made available to the investigators and were re-analysed by sex and age
      group in Maori and non-Maori using multivariate modelling. RESULTS: There was a
      total of 44 830 people in the combined study populations, of whom 6926 (15.4%)
      were Maori. There was significant variation in the populations sampled and
      instruments used for measuring alcohol; however, the relative differences in
      consumption patterns between Maori and non-Maori were similar across all studies.
      In all age groups, and in men and women, non-Maori were more likely to be
      drinkers. The strength of this relationship increased with age. In all age
      groups, frequency of alcohol consumption (days a year) was higher for non-Maori,
      though the relative volume drunk on a usual drinking occasion was consistently
      around 40% less than for Maori. The averaged daily volume of alcohol consumed was
      similar between Maori and non-Maori. CONCLUSIONS: Maori have markedly different
      alcohol consumption patterns from non-Maori, which are not apparent when averaged
      daily alcohol consumption is compared. Frequency of drinking and amount consumed
      on a typical drinking occasion should be considered when determining the
      relationship between Maori alcohol consumption and health-related problems.

PMID- 14583804
TI  - Antidepressant poisoning deaths in New Zealand for 2001.
AB  - AIM: To compare the rates of death per volume of drug dispensed for
      antidepressants in New Zealand. METHODS: Deaths from antidepressant poisonings
      were identified from the reports of coronial inquiries for New Zealand in 2001.
      Prescriptions for antidepressant medications were identified from the PharmHouse
      database from 1 January 2001 to 31 December 2001. The rates of deaths (95% CI)
      per prescription, tablet/capsule or defined daily dose were calculated for
      individual antidepressants and classes of antidepressant. RESULTS: There were 200
      poisoning deaths recorded in the database for New Zealand in 2001.
      Antidepressants were involved in 41 deaths, and death was attributed to an
      antidepressant in 23 cases. There were 5.52 (95% CI 3.85-7.68) deaths per 100 000
      prescriptions for tricyclic antidepressants (TCAs) and 2.51 (1.57-3.79) deaths
      per 100 000 prescriptions for selective serotonin reuptake inhibitors (SSRIs).
      There was marked variability in rates of death per volume of drug dispensed
      between individual antidepressants. CONCLUSIONS: SSRIs have lower rates of death
      per volume of drug dispensed than TCAs and there is also variation in these rates
      within these classes of drugs. Toxicity in overdose should be considered when
      prescribing antidepressants.

PMID- 14583805
TI  - Epidemiology of slipped capital femoral epiphysis in a population with a high
      proportion of New Zealand Maori and Pacific children.
AB  - AIM: To describe the epidemiology of slipped capital femoral epiphysis in NZ
      Maori and Pacific children residing in Auckland compared with NZ European
      children. METHODS: The charts and radiographs of 211 children admitted with 307
      slipped capital femoral epiphyses to Starship Children's Hospital between 1988
      and 2000 were reviewed. RESULTS: The average age at first presentation was 132.6
      +/-16.7 months in girls (range 95 to 170 months) and 149.5 +/- 19.3 months in
      boys (range 99 to 190 months), p <0.05. The age at presentation was not
      statistically different between the three ethnic groups. One hundred and seventy
      one children (81%) presented with a unilateral slipped capital femoral epiphysis.
      Forty children presented with bilateral simultaneous slipped capital femoral
      epiphyses; however, after two years of follow up, a further 56 children had been
      readmitted for pinning of the opposite hip, giving an overall rate of bilateral
      hip pinning of 45.5%. The relative racial frequency of slipped capital femoral
      epiphysis in the New Zealand Maori and the Pacific population was 4.2 times and
      5.6 times the New Zealand European population, respectively. CONCLUSIONS:
      Children as young as eight years are now presenting with slipped capital femoral
      epiphyses. General practitioners should be aware of the possibility of this
      diagnosis, particularly in children of NZ Maori or Pacific ethnicity.

PMID- 14583806
TI  - The Auckland Breast Cancer Register: a special project of the Auckland Breast
      Cancer Study Group.
AB  - AIMS: The Auckland Breast Cancer Register (ABCR) has been established in response
      to the need for a comprehensive database of breast cancer cases from the Auckland
      area. METHODS: The database records patient demographics, diagnosis, treatment
      options, prognosis and long-term outcome (annual follow up). Data from 1204
      cases, recorded between June 2000 and June 2002 are reported. RESULTS: The major
      findings are that 34% of women had breast cancer detected by screening only (47%
      in the group eligible for free screening within the Breast Screen Aotearoa
      screening programme); 84% of patients had invasive carcinoma; 13% had ductal
      carcinoma in situ (DCIS); and 3% fine needle aspiration only. Forty nine per cent
      of invasive tumours were < or =2 cm. Grade 3 tumours were found in 53% of
      patients under 40 years old compared with 26.8% 40 years or older. Mastectomy was
      performed in 56% of patients with invasive cancer and 33% of those with DCIS.
      Axillary surgery was performed in 94% of patients with invasive cancer and 39%
      had involved nodes. Seventy nine per cent of patients were referred for an
      opinion from an oncologist. Radiotherapy was given to 77% of these patients,
      chemotherapy to 33%, and hormone therapy to 57%. CONCLUSIONS: The ABCR will
      provide essential healthcare information that will lead to better understanding
      of breast cancer in Auckland and more effective delivery of the clinical
      resources available in the Auckland region.

PMID- 14583807
TI  - Replacing sugar-based soft drinks with sugar-free alternatives could slow the
      progress of the obesity epidemic: have your Coke and drink it too.

PMID- 14583808
TI  - New Zealand's first fatality linked to use of 1,4-butanediol (1,4-B, Fantasy): no
      evidence of coingestion or comorbidity.

PMID- 14583809
TI  - Clozapine-associated polyserositis.

PMID- 14583810
TI  - Gonad development characteristics and sex ratio in triploid Chinese shrimp (
      Fenneropenaeus chinensis).
AB  - This paper details for the first time the gonad development characteristics and
      sex ratio of triploid shrimp ( Fenneropenaeus chinensis). In triploid shrimp the
      development of gonad is apparently impaired, especially in females. In the ovary
      of triploids, germ cells mainly remain at oogonia stage during September through
      December. From January to February of the next year, partial primary oocytes
      developed in the ovary lobes. Spermatocytes and spermatids could be observed in
      the testes of triploids, and a few sperm were observed in the vas deferens and
      spermatophores. The morphology of sperms in triploid shrimp was abnormal. Flow
      cytometry was used to detect the ploidy of sperm in the vas deferens. The data
      showed that triploidy could affect the sex ratio in Chinese shrimp. The female-to
      male ratio in triploids of about 4:1 will favor triploid shrimp aquaculture.

PMID- 14583811
TI  - Marine pharmacology in 2000: marine compounds with antibacterial, anticoagulant,
      antifungal, anti-inflammatory, antimalarial, antiplatelet, antituberculosis, and
      antiviral activities; affecting the cardiovascular, immune, and nervous systems
      and other miscellaneous mechanisms of action.
AB  - During 2000 research on the pharmacology of marine chemicals involved
      investigators from Australia, Brazil, Canada, Egypt, France, Germany, India,
      Indonesia, Israel, Italy, Japan, the Netherlands, New Zealand, Phillipines,
      Singapore, Slovenia, South Korea, Spain, Sweden, Switzerland, United Kingdom, and
      the United States. This current review, a sequel to the authors' 1998 and 1999
      reviews, classifies 68 peer-reviewed articles on the basis of the reported
      preclinical pharmacologic properties of marine chemicals derived from a diverse
      group of marine animals, algae, fungi, and bacteria. Antibacterial,
      anticoagulant, antifungal, antimalarial, antiplatelet, antituberculosis, or
      antiviral activity was reported for 35 marine chemicals. An additional 20 marine
      compounds were shown to have significant effects on the cardiovascular and
      nervous system, and to possess anti-inflammatory or immunosuppressant properties.
      Finally, 23 marine compounds were reported to act on a variety of molecular
      targets and thus could potentially contribute to several pharmacologic classes.
      Thus, as in 1998 and 1999, during 2000 pharmacologic research with marine
      chemicals continued to contribute potentially novel chemical leads to the ongoing
      global search for therapeutic agents in the treatment of multiple disease
      categories.

PMID- 14583812
TI  - Temporal transcription of two antennapedia class homeobox genes in the marine
      copepod Calanus helgolandicus.
AB  - DNA sequence information has been obtained for 2 genes implicated in playing
      critical roles in copepod development. The first ( Cal-antp) was obtained by
      screening a Calanus helgolandicus genomic library. It shows homology to
      Antennapedia homeobox genes from a number of organisms including the centipede
      (76.8% over 250 bp) and the brine shrimp (75.5% over 220 bp). A second sequence
      (Hox 12) was obtained through reverse transcription polymerase chain reaction
      (PCR) of a solid-phase cDNA library constructed from Calanus eggs, and subsequent
      inverse PCR using a genomic DNA template. The Hox 12 sequence is homologous to
      the Antennapedia class of genes and shares homology with the chicken HoxB3 gene
      (71% over 187 bp) and with the fruit fly Sex Combs Reduced ( Scr) homeotic gene
      (66% identity over 223 bp). Using sequence data from Cal-Antp and Hox 12,
      specific primers were designed to investigate the temporal expression of these
      genes by PCR analysis of 10 stage-specific cDNA libraries.

PMID- 14583827
TI  - Peter Hirsch and biofilms: microbial ecology's role in a "new" field.

PMID- 14583813
TI  - Cloning of two crustacean hyperglycemic hormone isoforms in freshwater giant
      prawn (Macrobrachium rosenbergii): evidence of alternative splicing.
AB  - A full-length chh cDNA was cloned from the eyestalk of Macrobrachium rosenbergii.
      The 991-bp cDNA contains an open reading frame of 408 bp that encodes the prepro
      CHH. The tissue-specific expression pattern was examined by reverse transcriptase
      polymerase chain reaction. Positive signals were detected in the eyestalk, heart,
      gills, antennal glands, and thoracic ganglion but not in muscle and
      hepatopancreas. However, two types of products were observed. The nucleotide
      sequences revealed the existence of 2 chh transcripts, named chh and chh- l,
      respectively. Direct sequence evidence suggests that these two isoforms come from
      a Chh gene transcribed in an alternative splicing manner. The Mar-Chh gene
      consists of 4 exons. The eyestalk transcript (chh) contains exons I, II, and IV,
      whereas the chh-l transcript in heart, gills, antennal glands, and thoracic
      ganglion contains all 4 exons. The appearance of exon III in chh-l cDNA changes
      the sequence content in the latter half of the mature peptide, starting within
      the codon of the 40th residue, arginine. The amino acid sequence deduced from
      exon III matched no homologue in public protein databases, while the 2 cysteine
      residues in this segment preserved the positional conservation characters of CHH
      neuropeptide family members. The common organization of Chh genes between
      palaemonid, brachyuran, and astacus crustaceans suggests that the Chh gene has a
      4-exon structure in these species.

PMID- 14583830
TI  - Health-related quality of life in children attending a cardiology clinic.
AB  - Our purpose was to evaluate the impact of suspicion or confirmation of heart
      disease on the physical and psychosocial health of children. We utilized the
      Child Health Questionnaire (CHQ PF-50). Children ages 5 to 18 years attending a
      general cardiology clinic were eligible. Those with primary noncardiac diagnoses
      unrelated to heart disease were excluded. Children with similar conditions were
      grouped together for analysis. Group and subgroup means were compared to a U.S.
      population normative sample using the two-sample t test. The CHQ was administered
      to 321 patients (median age, 10.6 years). Overall, parents reported mean Physical
      and Psychosocial Summary Scores comparable to those for the normative sample
      (mean, 51.5 vs 53.0, p = 0.04; mean, 52.3 vs 51.2, p = 0.10). There was a trend
      toward worse physical health in most subgroups, especially those with
      cardiomyopathy (CM) (46.5; p = 0.01), and a comparable trend toward better
      psychosocial health except in those requiring major interventions. In subscale
      analyses, most subgroups reported worse Physical Functioning than the normative
      sample, especially CM (85.1 vs 96.1; p = 0.02). Parents of children with CM (53.2
      vs 73.0; p = 0.002) and the intervention subgroups (except minor) reported worse
      General Health Perceptions. Parents experienced increased Parental Impact
      Emotional, especially parents of children undergoing evaluations for chest pain
      (62.5 vs 80.3; p = 0.007). Most parents reported comparable or better health for
      the Family Cohesion and Bodily Pain subscales. Generally, parents of children
      attending a cardiology clinic report physical and psychosocial health comparable
      to that for the general U.S. population. However, diagnosis or confirmation of
      heart disease resulted in worse physical functioning and health perceptions and a
      significant negative emotional impact on parents.

PMID- 14583832
TI  - Multidetector row computed tomography for follow-up of patients with coronary
      artery aneurysms due to Kawasaki disease.
AB  - Multidetector row computed tomography (MDCT) coronary angiography was performed
      using a 16-slice MDCT scanner in three children with coronary aneurysms due to
      Kawasaki disease. Patients were given a beta-blocker. Following contrast
      injection, all data were acquired during a 20-second breathhold. Results were
      compared with those of conventional coronary angiography performed previously.
      MDCT provided clear visualization of coronary artery aneurysms, with coronary
      calcifications but which had not yet progressed to stenotic lesions. Because MDCT
      allows noninvasive detection and exclusion of coronary obstructions, it may be
      able to replace repeat conventional angiography as a follow-up study for children
      with coronary artery disease.

PMID- 14583831
TI  - Impaired left ventricular function after arterial switch operation: exclusion of
      significant coronary artery stenosis with an intravascular Doppler guidewire.
AB  - Patients after arterial switch operation for transposition of the great arteries
      are at risk for coronary artery stenosis or obstruction due to intraoperative
      manipulation. This case describes an infant with impaired left ventricular
      function 8 months after arterial switch operation. A hemodynamically significant
      left coronary artery stenosis was excluded by determination of coronary flow
      reserve using an intravascular Doppler guidewire.

PMID- 14583833
TI  - Neonatal aortic arch thrombosis masquerading as coarctation of the aorta.
AB  - We report two neonates with thrombosis of the aortic arch and isthmus diagnosed
      by echocardiography. Neonatal transient protein C deficiency was present in one
      patient and the other patient had severe perinatal asphyxia. Both patients
      presented with markedly reduced left ventricular function and severe aortic
      obstruction. In one infant, the thrombus was successfully removed surgically, and
      the second infant died due to serious complications of perinatal asphyxia.

PMID- 14583834
TI  - Right superior vena cava draining predominantly into the left atrium causing
      cyanosis in a young child.

PMID- 14583835
TI  - Permanent transvenous dual-chamber pacing using the coronary sinus in a patient
      with a mechanical prosthetic tricuspid valve.
AB  - Ventricular pacing in patients with mechanical prosthetic tricuspid valves
      usually requires an epicardial approach. Epicardial pacing requires at least a
      limited thoracotomy and long-term pacing thresholds are generally inferior to
      thresholds achieved with transvenous pacing. This case report describes the use
      of a coronary sinus lead designed for left ventricular pacing as the sole
      ventricular lead in a dual-chamber pacing system in a young male with persistent
      complete atrioventricular block following remote ventricular septostomy and
      mechanical tricuspid valve replacement. With the development of dedicated,
      transvenous, left ventricular leads with stable positions and reliably low
      thresholds, ventricular pacing via the coronary sinus is a viable option when
      right ventricular pacing is impossible.

PMID- 14583837
TI  - Ultrastructure of dental enamel afflicted with hypoplasia: an atomic force
      microscopic study.
AB  - The ultrastructure of the human tooth enamel from a patient diagnosed with
      hypoplasia (HYP) was investigated using atomic force microscopy (AFM) and
      compared with the surface of normal human tooth enamel. Hypoplasia is a
      hereditary defect of dental enamel in which the enamel is deficient in either
      quality or quantity. AFM results presented for the HYP tooth enamel clearly
      demonstrate that the apatite crystal morphology in hypoplasia tooth enamel is
      perturbed in the diseased state which could result from a defective synthesis of
      the extracellular matrix proteins, e.g., amelogenin, by the ameloblasts. HYP
      enamel consisting of loosely packed, very small grains does not present a
      tendency for association, as in the case of the normal healthy tooth. Indeed, the
      enamel surface affected by HYP is porous and is made of much smaller grains. In
      some samples, the HYP part of enamel surface appeared in the form of a point
      defect, which we believe may be associated with the early stages of the HYP
      deformation.

PMID- 14583836
TI  - Transcatheter occlusion of a large left coronary artery to right superior vena
      cava fistula using the Amplatzer duct occluder device.
AB  - Transcatheter embolization has become the therapy of choice for most coronary
      artery fistula. We report a 5.9-kg infant with a coronary artery fistula from the
      left coronary artery to the right superior vena cava with significant congestive
      heart failure. The infant underwent successful complete occlusion using the
      Amplatzer duct occluder.

PMID- 14583838
TI  - Measurements of bone mineral density of the radius in a medieval population.
AB  - The current morbidity in the elderly as a result of osteoporotic fractures has
      led to interest in the incidence of this condition in past populations. The
      purpose of this study was to evaluate the technique of scanning of the distal
      radius with DXA in archaeological bone. The radius is often better preserved in
      archaeological contexts than bone with higher trabecular content such as the
      femoral neck or vertebrae. Adult radii (101) from the deserted medieval village
      site of Wharram Percy were scanned. These skeletal remains represent an
      homogenous rural population. The scanned individuals were divided into 3 age
      groups; 18-29, 30-49, and 50+. In both males and females bone loss was
      statistically significant in the highly trabecular ultra-distal region and the
      more cortical mid-region after age 50. Only females lost bone in the largely
      cortical one-third site before age 50. This is in accordance with modern clinical
      studies in which this loss is attributed to the effects of menopause. In order to
      assess whether there were differences in bone loss between weight and non-weight
      bearing bones, the results were also compared with those from an earlier study of
      the femoral neck. In both sexes trabecular bone was lost at both anatomical sites
      after age 50. However, scanning the radius also had the advantage of assessing
      cortical bone loss. Additionally, despite demonstrable bone loss, there were no
      Colles or hip fractures in this paleopopulation, suggesting that although an
      active lifestyle such as that spent in agricultural activity, does not prevent
      bone loss, it may protect against osteoporotic fracture.

PMID- 14583839
TI  - Immunocytochemical evidence on the effects of glucocorticoids on type I collagen
      synthesis in human osteoblastic cells.
AB  - The effects of glucocorticoids on DNA synthesis and cellular function were
      assessed in cultures of human osteoblastic cells by using indirect
      immunoperoxidase staining with a type I antiprocollagen antibody and by measuring
      procollagen type I N and C propeptides (PINP, PICP) in the culture medium by
      radiometric methods. Likewise, we analyzed the correlation between intracellular
      immunostaining and procollagen propeptides released into the culture medium, as
      well as the correlation between PINP and PICP. Human osteoblasts were cultured
      with and without addition of dexamethasone (DEX) at two supraphysiological
      concentrations, 10(-6) M and 10(-7) M, for 24 and 48 h. Treatment with DEX at 10(
      6) M was associated with a significant decrease in the percentage of cells
      showing intracellular type I procollagen immunoreactivity at 24 and 48 h ( P <
      0.05). Similar effects were observed with 10(-7) M DEX. Dexamethasone 10(-6) M
      and 10(-7) M also induced significant decreases in PINP and PICP values after 24
      and 48 h of treatment ( P < 0.05). The decrease in intracellular procollagen
      immunoreactivity and propeptide secretion was not associated with a reduction in
      DNA synthesis. A highly significant correlation was observed between the values
      of PINP and PICP in the culture medium as well as between the values of
      intracellular immunostaining and PINP and PICP ( P < 0.001). In conclusion, our
      results suggest that supraphysiological doses of glucocorticoids produce a direct
      inhibition on osteoblastic function through their effect on type I procollagen
      synthesis. Immunoperoxidase detection of type I intracellular procollagen as well
      as the quantification of PINP and PICP in the culture medium are reliable methods
      of assessing osteoblast function.

PMID- 14583840
TI  - Unanticipated changes in steady-state mRNA levels for glyceraldehyde-3-phosphate
      dehydrogenase in rat tibiae.
AB  - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA levels are commonly used as
      an internal control to normalize gene expression data based on the belief that
      this gene is constitutively expressed. However, GAPDH mRNA levels increased by
      more than 2.5-fold in tibiae of hindlimb unloaded female rats compared to L32
      mRNA levels. Similarly, GAPDH mRNA levels increased compared to 18S ribosomal
      RNA. Treatment with growth hormone and alcohol show no disparity in GAPDH mRNA
      levels whereas in some experiments, parathyroid hormone and 17beta-estradiol
      increased GAPDH mRNA levels. Taken together, these findings indicate that it is
      essential to demonstrate that GAPDH expression is not altered prior to using the
      gene as an internal control.

PMID- 14583841
TI  - Discrimination of patients with and without vertebral fractures as measured by
      ultrasound and DXA osteodensitometry.
AB  - This study compares dual X-ray absorptiometry (DXA) measurements of the hip and
      spine with quantitative ultrasound (QUS) parameters measured simultaneously at
      the calcaneal and phalangeal bone in 174 patients with and without vertebral
      fractures. The aim of this study was to compare the ability of DXA and QUS
      measurements to discriminate patients with and without osteoporotic vertebral
      fractures and to evaluate whether QUS measurements in addition to the DXA
      measurements improve the clinical discrimination between patients with and
      without osteoporotic vertebral fractures. T-scores determined by DXA measurements
      at the spine and hip and QUS measurements at the calcaneus provide similar
      information regarding the discrimination of women with and without vertebral
      fractures. Phalangeal QUS measurements did not discriminate between patients with
      and without vertebral fractures. The discriminative power of the combined use of
      DXA and calcaneal QUS measurements to discern between patients with and without
      vertebral fractures increases in women. In contrast, the combined use of DXA and
      phalangeal QUS measurements resulted in decreased discriminative power as
      compared to DXA measurements alone. The number of fractures was higher in the
      quartiles with lower T-scores of the DXA and calcaneal QUS measurements whereas
      no difference was seen in the T-score quartiles of the phalangeal QUS device.
      These findings suggest that DXA and QUS measurements at weight-bearing skeletal
      sites provide useful information for assessing women with an anamnestic risk of
      osteoporotic bone loss. For DXA and calcaneal QUS measurements in men as well as
      for phalangeal QUS, however, a clinical algorithm remains to be established to
      understand the diagnostic implications and related therapeutic consequences of
      the obtained measurements.

PMID- 14583845
TI  - A multi-investigator/institutional DNA bank for AIDS-related human genetic
      studies: AACTG Protocol A5128.
AB  - BACKGROUND: An understanding of the relationships among allelic variability and
      clinical outcomes will be critical if HIV-infected patients are to benefit from
      the explosion in knowledge in human genomics. Human DNA banks must allow future
      analyses while addressing confidentiality, ethical, and regulatory issues.
      METHOD: A multidisciplinary group of clinical investigators, ethicists, data
      managers, regulatory specialists, and community representatives developed Adult
      AIDS Clinical Trials Group (AACTG) Protocol A5128. Participants in past or
      present AACTG clinical trials may contribute DNA. Extraction from whole blood is
      performed at a central laboratory, where participants' unique identifiers are
      replaced by randomly assigned identifiers prior to DNA storage. To identify
      genotype-phenotype relationships, genetic assay results can be temporarily linked
      to clinical trials data. RESULTS: Institutional review boards in 21 states and
      Puerto Rico have approved Protocol A5128, and accrual is ongoing. Of the first
      4,247 enrollees, 82% are male, 56% are white, 26% are African American, and 15%
      are Hispanic. Because participants may participate in multiple AACTG protocols,
      these represent 11,424 cases in 324 different AACTG studies and substudies, with
      at least 100 participants from 24 different studies. Studies exploring specific
      genotype-phenotype relationships are underway. CONCLUSION: The AACTG DNA bank
      will be an important resource for genomic discovery relevant to HIV therapy.

PMID- 14583846
TI  - Clinical impact of double protease inhibitor boosting with lopinavir/ritonavir
      and amprenavir as part of salvage antiretroviral therapy.
AB  - PURPOSE: Double protease inhibitor (PI) boosting is being explored as a new
      strategy in salvage antiretroviral (ARV) therapy. However, if a negative drug
      interaction leads to decreased drug levels of either or both PIs, double PI
      boosting could lead to decreased virologic response. A negative drug interaction
      has been described between amprenavir (APV) and lopinavir/ritonavir (LPV/r). This
      observational cohort study assessed the virologic impact of the addition of APV
      to a salvage ARV regimen, which also contains LPV/r, compared to a regimen
      containing LPV/r alone. METHOD: Patients initiated on a salvage ARV regimen that
      included LPV/r obtained from the expanded access program in Toronto, Canada, were
      evaluated. APV (600-1,200 mg bid) was added at the discretion of the treating
      physician. RESULTS: Using multivariate Cox proportional hazards models, we found
      that the addition of APV to a LPV/r-containing salvage regimen was not
      significantly associated with time to virologic suppression (< 50 copies/mL;
      adjusted hazard ratio [HR] = 0.75, p =.12) or with time to virologic rebound
      (adjusted HR = 1.46, p =.34). Those patients who received higher doses of APV had
      an increased chance of virologic suppression (p =.03). In a subset of 27
      patients, the median LPV C(trough) was significantly lower in patients receiving
      APV (p =.04), and the median APV C(trough) was reduced compared to reported
      controls. CONCLUSION: Our data do not support an additional benefit in virologic
      reduction of double boosting with APV and LPV/r relative to LPV/r alone in
      salvage ARV therapy. Our study's limitations include its retrospective nature and
      the imbalance between the two groups potentially confounding the results.
      Although these factors were adjusted for in the multivariate analysis, a
      prospective randomized controlled trial is warranted to confirm our findings.

PMID- 14583847
TI  - Predictors of long-term immunological outcome in rebounding patients on protease
      inhibitor-based HAART after initial successful virologic suppression:
      implications for timing to switch.
AB  - OBJECTIVE: To assess predictive factors of long-term immune restoration in
      patients who started protease inhibitor (PI)-based HAART and experienced
      virological rebound after initial complete success. METHOD: A retrospective
      longitudinal analysis of all HIV-infected patients who started their first PI
      based HAART and reached viral load below 500 copies/mL was carried out in a large
      academic center in Italy. Patients were classified either as complete virologic
      responder (CR) or rebounders (REB) when confirmed plasma viremia was detected
      thereafter. Immunological outcome was the area under the curve (AUC) of the
      absolute CD4+ cell count change since the 8th month after treatment initiation
      (CD4+ T-cell AUC). Association between baseline characteristics, virological
      outcome, and CD4+ T-cell AUC was assessed by univariate and multivariate
      analysis. RESULTS: There were 374 patients who were included in the study. Mean
      follow-up was 30.2 months. There were 226/374 patients (60.4%) who remained CR
      while 148/374 (39.6%) presented at least one rebound (REB). Among REB patients,
      complete viral suppression was regained in 15/42 (35.7%) and 50/106 (47.1%)
      patients who underwent therapy changes or not, respectively. When multiple linear
      regression was carried out, previous nucleoside reverse transcriptase inhibitor
      (NRTI) experience and baseline CD4+ cell count below 350 cells/muL did not impair
      long-term immune restoration. The occurrence of rebound, its duration (> 18
      months), and its magnitude (peak of viral load > 10,000 copies/mL) were
      independent negative prognostic factors. CONCLUSION: The occurrence of viral
      rebound is independently associated with significantly impaired long-term
      immunological restoration. The magnitude of viral rebound (< 10,000 copies/mL)
      and its duration (< 18 months) may be useful to identify those rebounding
      patients who may still profit from maintaining the current failing therapy if a
      more aggressive approach may be expected to be deleterious for tolerability
      reasons or lack of options.

PMID- 14583849
TI  - Impact of various antiretroviral drugs and their plasma concentrations on plasma
      lipids in heavily pretreated HIV-infected patients.
AB  - OBJECTIVE: To evaluate the frequency and the magnitude of lipid abnormalities
      (LA) in respect to the nature of the antiretroviral drug and its plasma
      concentrations. PATIENTS/METHOD: Trough concentrations (C(trough)) of protease
      inhibitors (PIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) were
      assessed at Weeks 4, 8, 24, 28, and 32. Fasting triglycerides (TG) and total
      cholesterol (CH) were sampled at Weeks 0, 12, 20, and 32. We analyzed the
      probability of occurrence of grade 3-4 CH (> 7.8 mmol/L) and TG (> 8.4 mmol/L)
      during a 24-week period according to the drug taken using a Kaplan-Meier analysis
      and log rank test. Relation between Week 8 PI or NNRTI C(trough) and Week 12
      lipid levels was assessed using the Kendall correlation measure. RESULTS: The
      PharmAdapt study included 252 patients (mean age 41 years, 83% males); the
      patients received a PI (73%), an NNRTI (50%), and/or a ritonavir (RTV) booster
      containing (46%) regimen. Compared to any other regimen, use of lopinavir
      (LPV)/RTV or efavirenz (EFV) was associated with a higher risk of grade 3-4 CH.
      Use of LPV/RTV and RTV booster was associated with a higher risk of grade 3-4 TG.
      Use of any PI-containing regimen was associated with a higher risk for grade 3-4
      CH and TG compared to non PI-based regimens. Kendall correlation coefficients for
      PI or NNRTI C(trough) and blood lipid levels were close to zero for all drugs and
      CH or TG, showing the absence of relation between drug concentrations and lipid
      levels. CONCLUSION: Severity of lipid abnormalities is related to the nature of
      the antiretroviral drug. There is no short-term relation between PI or NNRTI
      trough concentrations and blood lipid levels in heavily pretreated patients.

PMID- 14583848
TI  - L-glutamine supplementation improves nelfinavir-associated diarrhea in HIV
      infected individuals.
AB  - PURPOSE: To determine whether L-glutamine decreases the severity of nelfinavir
      associated diarrhea in HIV-infected individuals. Other endpoints include the
      effect on quality of life, muscle-wasting syndrome, CD4 counts, and viral load.
      METHOD: HIV-infected patients with nelfinavir-associated diarrhea for >1 month
      were randomized to receive L-glutamine 30 g/day or placebo for 10 days in a
      prospective, double-blind, crossover study. Diarrhea was measured on a scale
      ranging from grade 0 (no diarrhea) to grade 4 (severe diarrhea, > 7 stools/day).
      Quality of life was assessed by the Medical Outcome Study (MOS) HIV
      questionnaire. RESULTS: Twenty-five participants completed the study. There was a
      significant difference between the L-glutamine and placebo arms on the mean grade
      of diarrhea (0.762 vs. 1.850, p <.01) when placebo was administered first. When L
      glutamine was administered first, there was a significant crossover effect (p
      <.02), with similar mean grades of diarrhea in the two groups. There was also a
      significant difference between L-glutamine and placebo in the mean change in MOS
      scores from baseline (1.48 vs. -2.19, p <.017). There were no significant
      differences between treatment groups for the other endpoints. CONCLUSIONS: In
      this population of HIV-positive participants, L-glutamine 30 g/day significantly
      (p <.01) reduced the severity of nelfinavir-associated diarrhea and produced
      improved quality of life compared with placebo.

PMID- 14583850
TI  - Relationship between low bone mineral density and highly active antiretroviral
      therapy including protease inhibitors in HIV-infected patients.
AB  - PURPOSE: The objectives of this study were to determine the prevalence of
      osteopenia and the factors associated with its presence in HIV-infected patients
      under highly active antiretroviral therapy (HAART) and to assess the changes of
      bone mineral density (BMD) in a population followed prospectively. METHOD: BMD
      was assessed by dual-energy X-ray absorptiometry (DEXA) scans at the lumbar spine
      and at the femoral neck in 78 HIV-infected patients who had previously received
      HAART as the first antiretroviral regimen and in 11 antiretroviral-naive HIV
      infected patients. BMD measurements were repeated in 70 treated patients who had
      completed 1 year of follow-up. RESULTS: Thirty-seven (42%) patients showed
      osteopenia at any localization. The prevalence of osteopenia in PI-naive patients
      was 23% versus 49% in individuals who had received PI at any moment [p =.001;
      adjusted odds ratio (95% CI) = 0.11 (0.02-0.48)]. The frequency of osteopenia was
      significantly higher among men than among women [50% vs. 17%; p =.016; adjusted
      OR (95% CI) = 12.1 (2.22-66.20)]. The level of plasma albumin was independently
      associated with osteopenia [adjusted OR (95% CI) per each g/dL of plasma albumin
      decrease 2.55 (1.18-10)]. In patients in whom a second DEXA was done, no
      significant changes in BMD were found. CONCLUSION: The prevalence of osteopenia
      in HIV-infected patients on HAART is high. Loss of BMD is associated with PI
      therapy, low plasma albumin level, and male sex. Osteopenia does not progress
      after 1 year of continued HAART.

PMID- 14583851
TI  - Patient acceptance of self-injected enfuvirtide at 8 and 24 weeks.
AB  - PURPOSE: Enfuvirtide is the first of a new class of antiretrovirals called the
      fusion inhibitors. It is administered twice daily by self-injection. This study
      assessed patient acceptance of enfuvirtide self-injection. METHOD: Patients (n =
      661, intent-to-treat [ITT]) in two ongoing phase 3 trials were surveyed at
      treatment Weeks 8 and 24 using the Subcutaneous Injection Survey. This validated
      instrument contains 18 items measuring patients' assessment of ease of injection,
      impact on daily functioning, and activities of daily living. RESULTS: The
      majority (65%-92%) of patients assessed all items relating to ease of injection
      as "very easy" or "easy" at both 8 and 24 weeks. Similarly, at both visits, the
      majority (69%-90%) of patients assessed their daily functioning as "not at all"
      or "a little" limited by enfuvirtide self-injection, and 96%-98% gave these
      assessments for impact on activities of daily living. CONCLUSION: These findings
      indicate that most patients taking enfuvirtide in clinical trials learn to
      integrate enfuvirtide dosing in their daily routines; with appropriate education
      and training, enfuvirtide self-injection becomes routine with relatively little
      subjective impact on daily functioning and activities of daily living. Patient
      acceptance of self-injected enfuvirtide is high and does not decline over 24
      weeks of therapy.

PMID- 14583852
TI  - Comparison of efficacy of efavirenz and nevirapine: lessons learned for cohort
      analysis in light of the 2NN Study.

PMID- 14583853
TI  - When is it mutualism?

PMID- 14583854
TI  - Interacting guilds: moving beyond the pairwise perspective on mutualisms.
AB  - Most textbook treatments imply, and almost all theoretical analyses assume, that
      mutualistic interactions take place between a single pair of interacting partner
      species. A major goal of this symposium is to broaden and shift this pairwise
      perspective and make it concordant with the emerging view that locally exclusive
      mutualisms between just two species are the exception and that many communities
      include guilds of mutualistic species on one or both sides of the interaction.
      Many pollination and seed-dispersal mutualisms have long been recognized as
      diffuse, but recent molecular analyses are revealing unrecognized partner
      diversity in mutualistic interactions previously thought to be locally species
      specific. Co-occurring species within a mutualist guild are unlikely to be
      ecologically equivalent in the way they locate, compete for, and/or reward
      partners, and so intraguild interactions have the potential to influence
      population dynamics and patterns of selection in species on both sides of the
      mutualistic interaction. To illustrate some of these potential complexities for
      population dynamics, I use simple path analytic models to show that positive
      pairwise interactions between mutualists do not necessarily translate into
      positive net interactions within a mutualism involving more than two species. For
      example, when there is intraguild competition for partners, or even for resources
      external to the mutualism, the presence of a lower-quality mutualist can
      negatively affect the partner population by reducing associations it can form
      with better mutualists. Variation in quality among potential partners is likely
      to place a premium on traits or behaviors that enhance association with better
      mutualists. More investigations are needed to determine how variation among
      interacting mutualists, with respect to characteristics such as longevity,
      dispersal capability, and competitive ability, influence population dynamics and
      selection in multispecies mutualisms.

PMID- 14583855
TI  - Ecological dynamics of mutualist/antagonist communities.
AB  - One approach to understanding how mutualisms function in community settings is to
      model well-studied pairwise interactions in the presence of the few species with
      which they interact most strongly. In nature, such species are often specialized
      antagonists of one or both mutualists. Hence, these models can also shed light on
      the problem of when and how mutualisms are able to persist in the face of
      exploitation. We used spatial stochastic simulations to model the ecological
      dynamics of obligate, species-specific mutualisms between plants and pollinating
      seed parasite insects (e.g., yuccas and yucca moths) in the presence of one of
      two obligate antagonist species: flower-feeding insects (florivores) or insects
      that parasitize seeds but fail to pollinate (exploiters). Our results suggest
      that mutualisms can persist surprisingly well in the presence of highly
      specialized antagonists but that they exhibit distinctly different temporal and
      spatial dynamics when antagonists are present. In our models, antagonists tend to
      induce oscillations in the mutualist populations. As the number of per capita
      visits by antagonists increase, the system's oscillatory dynamics become more
      extreme, finally leading to the extinction of one or more of the three species.
      When the antagonists exhibit high per capita visitation frequencies and long
      dispersal distances, significant spatial patchiness emerges within these
      tripartite interactions. We found surprisingly little difference between the
      ecological effects of florivores and exploiters, although in general florivores
      tended to drive themselves (and sometimes the mutualists) to extinction at
      parameter values at which the exploiters were able to persist. These theoretical
      results suggest several testable hypotheses regarding the ecological and
      evolutionary persistence of mutualisms. More broadly, they point to the critical
      importance of studying the dynamics of pairwise interactions in community
      contexts.

PMID- 14583856
TI  - Ecological persistence of the plant-mycorrhizal mutualism: a hypothesis from
      species coexistence theory.
AB  - In diverse mutualisms, it is common for potential partners to vary in the quality
      of benefits they provide. When weakly beneficial mutualists and parasites have a
      competitive advantage over strongly beneficial mutualists, it is not clear how
      strongly beneficial mutualists persist. If mutualism is destabilized by
      competitive superiority of weakly beneficial mutualists or cheaters, then
      mechanisms providing for stable coexistence among competing species may also
      provide for the persistence of mutualism. We analyze coexistence of species
      within a mutualist guild using a simple spatial model of patch occupancy to
      suggest hypotheses about the ecological persistence of mutualism in the
      interaction between plants and ectomycorrhizal fungi. We suggest that plants
      could facilitate the persistence of mutualistic mycorrhizal fungi by enhancing
      the mortality of root tips colonized by competitively superior and less
      mutualistic fungi. We also discuss previous empirical studies and present
      original data from field observations in plant-ectomycorrhizal systems to address
      our predictions and to suggest profitable avenues for further work.

PMID- 14583857
TI  - Multispecies microbial mutualisms on coral reefs: the host as a habitat.
AB  - Reef-building corals associate with a diverse array of eukaryotic and
      noneukaryotic microbes. Best known are dinoflagellates in the genus Symbiodinium
      ("zooxanthellae"), which are photosynthetic symbionts found in all reef-building
      corals. Once considered a single species, they are now recognized as several
      large, genetically diverse groups that often co-occur within a single host
      species or colony. Variation among Symbiodinium in host identities, tolerance to
      stress, and ability to colonize hosts has been documented, but there is little
      information on the ecology of zooxanthellar free-living stages and how different
      zooxanthellae perform as partners. Other microbial associates of reef corals are
      much less well known, but studies indicate that individual coral colonies host
      diverse assemblages of bacteria, some of which seem to have species-specific
      associations. This diversity of microbial associates has important evolutionary
      and ecological implications. Most mutualisms evolve as balanced reciprocations
      that allow partners to detect cheaters, particularly when partners are
      potentially diverse and can be transmitted horizontally. Thus, environmental
      stresses that incapacitate the ability of partners to reciprocate can destabilize
      associations by eliciting rejection by their hosts. Coral bleaching (the loss of
      zooxanthellae) and coral diseases, both increasing over the last several decades,
      may be examples of stress-related mutualistic instability.

PMID- 14583858
TI  - Competition and coexistence: exploring mechanisms that restrict and maintain
      diversity within mutualist guilds.
AB  - Mutualistic interactions are diverse and widespread and often involve
      multispecies guilds of mutualists competing for access to one or more partner
      species. Despite the ubiquity of these interactions, we know little about the
      dynamics of competition and coexistence within these guilds or how interactions
      between mutualists and their shared resource (the partner species) may influence
      these dynamics. In this article, we review the evidence for interspecific
      competition for partners within mutualist guilds in both plant-pollinator and ant
      myrmecophyte systems. We then review evidence for the operation of different
      coexistence mechanisms within these guilds and discuss how the dynamics of
      competition and coexistence may be uniquely shaped by multispecies mutualist
      interactions. In particular, we note that adaptive and plastic responses by
      mutualists to variation in partner quality are likely to play an important role
      in determining these dynamics. We summarize by considering the ecological
      conditions that are likely to restrict or promote species coexistence within
      mutualist guilds. We suggest that these guilds may provide powerful model systems
      for exploring multiple mechanisms of species coexistence, and we discuss how
      these mechanisms may be modified by evolutionary adaptation.

PMID- 14583859
TI  - Coevolution in variable mutualisms.
AB  - Many mutualistic interactions are probably not mutualistic across all populations
      and years. This article explores consequences of this observation with a series
      of genetic models that consider how variable mutualisms coevolve. The first
      models, previously introduced in a general coevolutionary context, consider two
      coevolving species whose fitness interactions change between beneficial and
      antagonistic in response to independent spatial or temporal variation in the
      abiotic or biotic environment. The results demonstrate that both temporal and
      spatial variability in fitness interactions can cause partner species with
      tightly matched traits favored by unconditional mutualisms to be vulnerable to
      evolutionary invasion by alternative types. A new model presented here shows that
      an additional mutualistic species can have a similar effect and can even cause
      fitness interactions between the other two species to evolve. Under some
      conditions, the pairwise interactions can change unidirectionally from
      mutualistic to antagonistic, with virtually no evolutionary change in either
      partner species. In other cases, fitness interactions between the species pair
      can oscillate between mutualism and antagonism as a result of coevolution in the
      third species. Taken as a whole, these theoretical results suggest that many
      features of mutualistic coevolution can best be understood by considering
      spatial, temporal, and community-dependent patterns of fitness interactions.

PMID- 14583860
TI  - Invasive pneumococcal disease in Scotland, 1999-2001: use of record linkage to
      explore associations between patients and disease in relation to future
      vaccination policy.
AB  - A record linkage study was done to provide comprehensive data on the
      epidemiologic characteristics of invasive pneumococcal disease (IPD) in Scotland.
      The overall incidence of IPD was 11 cases/10(5) persons and 21 cases/10(5)
      persons <1 year of age, 51 cases/10(5) persons 1 year of age, 45 cases/10(5)
      elderly persons (age > or =65 years), 176-483 cases/10(5) persons with chronic
      medical conditions, and 562-2031 cases/10(5) persons with severe
      immunosuppression. The case-fatality rate was 11% among elderly persons and
      ranged from 3% to 13% among persons with underlying medical conditions. The most
      common pneumococcal serogroups associated with IPD were 14, 9, 6, 19, 23, 8, and
      4. Serogroups included in the 23-valent polysaccharide vaccine caused the
      majority of cases of IPD. The proportion of IPD due to the 7-, 9-, and 11-valent
      conjugate vaccine serogroups was lower among older people and persons with
      underlying medical conditions.

PMID- 14583861
TI  - Epidemiologic investigation of a restaurant-associated outbreak of Pontiac fever.
AB  - This case-control study investigated a cluster of respiratory illness among
      patrons of a restaurant. Of 173 patrons interviewed, 117 (68%) were ill. Symptoms
      included myalgias (93%), headache (87%), and fatigue (79%). The mean incubation
      period was 49 h and the mean duration of illness was 71 h. Patrons aged >15 years
      were more likely to have been ill than younger patrons (odds ratio [OR], 2.96;
      P=.002); 58% of persons who were ill sat near a large fountain, compared with 18%
      of respondents who were not ill (OR, 7.5; P=.005). Legionella anisa was cultured
      from water samples obtained from the fountain pool. Of 22 individuals who were
      ill, 11 (50%) had a > or =4-fold increase in the titer of antibody to that strain
      of L. anisa from acute-phase to convalescent-phase serum samples; 3 others (14%)
      had persistently elevated titers of > or =512; of a group of 20 individuals who
      had not been exposed to the restaurant, none had titers of >128. Pontiac fever
      should be considered as a diagnosis during acute outbreaks of influenza-like
      illness with a high attack rate and no other identified etiology.

PMID- 14583862
TI  - Once-weekly dalbavancin versus standard-of-care antimicrobial regimens for
      treatment of skin and soft-tissue infections.
AB  - Dalbavancin, a novel glycopeptide with a long elimination half-life (
      approximately 9-12 days), was compared to standard antimicrobial therapy for skin
      and soft-tissue infections (SSTIs). In a randomized, controlled, open-label,
      phase 2 proof-of-concept trial, adults received 1100 mg of dalbavancin (as a
      single intravenous infusion), 1000 mg of dalbavancin intravenously and then 500
      mg intravenously 1 week later, or a prospectively defined standard-of-care
      regimen. A gram-positive pathogen was isolated from samples obtained from 41
      (66%) of 62 patients at baseline; Staphylococcus aureus was the most prevalent
      species (83% of pathogens). Clinical success rates at a follow-up visit (test of
      cure) were 94.1% among patients treated with 2 doses of dalbavancin, 61.5% among
      patients treated with 1 dose of dalbavancin, and 76.2% among patients treated
      with a standard-of-care regimen. All treatment regimens were well tolerated; drug
      related adverse reaction rates were similar across the 3 groups. These findings
      suggest that a regimen of 2 doses of dalbavancin administered 1 week apart is
      effective in the treatment of complicated, gram-positive bacterial SSTIs and
      warrants further study.

PMID- 14583863
TI  - Successful treatment of Balamuthia amoebic encephalitis: presentation of 2 cases.
AB  - Case histories are presented of 2 individuals (a 5-year-old girl and 64-year-old
      man) who developed encephalitis caused by the free-living amoeba Balamuthia
      mandrillaris. Both individuals survived after diagnosis and initiation of
      effective antimicrobial therapy. Immunostaining for Balamuthia-specific antibody
      levels identified the causative agent of the infections. Antimicrobial therapy
      with flucytosine, pentamidine, fluconazole, sulfadiazine, and a macrolide
      antibiotic (azithromycin or clarithromycin) was initiated. Phenothiazines
      (thioridazine and trifluoperazine) were also used. Both patients recovered, and
      there was no evidence of recrudescence of the disease at 2 and 6 years after
      onset of symptoms. Awareness of Balamuthia as the causative agent of encephalitis
      and early initiation of antimicrobial therapy were critical to the recovery of
      both patients. Although optimal antimicrobial therapy for Balamuthia amoebic
      encephalitis has yet to be determined, the antimicrobials used in these 2 cases
      effectively controlled the disease. These 2 individuals are the only known
      survivors of this otherwise fatal type of amoebic encephalitis.

PMID- 14583864
TI  - Hospital transmission of community-acquired methicillin-resistant Staphylococcus
      aureus among postpartum women.
AB  - Infections caused by community-acquired methicillin-resistant Staphylococcus
      aureus (CA-MRSA) are being increasingly observed in patients who lack traditional
      risk factors. We described 8 postpartum women who developed skin and soft-tissue
      infections caused by MRSA at a mean time of 23 days (range, 4-73 days) after
      delivery. Infections included 4 cases of mastitis (3 of which progressed to
      breast abscess), a postoperative wound infection, cellulitis, and pustulosis. The
      outbreak strains were compared with the prototype CA-MRSA strain MW2 and found to
      be indistinguishable by pulsed-field gel electrophoresis. All were spa type 131,
      all contained the staphylococcal chromosomal cassette mec type IV, and all
      expressed Panton-Valentine leukocidin and staphylococcal enterotoxins C and H.
      The route of transmission was not discovered: the results of surveillance
      cultures of samples obtained from employees of the hospital, the hospital
      environment, and newborns were negative for the outbreak strain. We report that
      MW2, which was previously limited to the midwestern United States, has spread to
      the northeastern United States and has become a health care-associated pathogen.

PMID- 14583865
TI  - Non-organ-specific autoantibodies in children with chronic hepatitis C: clinical
      significance and impact on interferon treatment.
AB  - We evaluated the prevalence and clinical significance of non-organ-specific
      autoantibodies (NOSAs) in 47 hepatitis C virus (HCV)-positive children with
      abnormal alanine transaminase levels and analyzed the association between NOSAs
      and virus level, genotype, human leukocyte antigen status, and interferon (IFN)
      response. Forty-two hepatitis B virus (HBV)-positive children and 25 age- and sex
      matched healthy children served as control subjects. NOSAs were found in 34% of
      the HCV-positive children, 12% of the HBV-positive controls, and none of the
      healthy control subjects. Liver-kidney microsomal antibody type 1 (LKM1) was
      detected in 11% of the HCV-positive children but in none of the controls. The HCV
      load was significantly higher in NOSA-negative than in NOSA-positive children.
      HCV genotype distribution and human leukocyte antigen alleles were similar,
      irrespective of NOSA status. Long-term response to IFN therapy was achieved by
      18% of the NOSA-positive and 55% of the NOSA-negative subjects. Two LKM1-positive
      children developed acute, self-limited hepatocellular necrosis while receiving
      IFN therapy. NOSAs are frequently present in children with hepatitis C, who are
      less likely to benefit from IFN therapy.

PMID- 14583866
TI  - The pathology of rotavirus-associated deaths, using new molecular diagnostics.
AB  - Rotavirus, the most common cause of severe, dehydrating gastroenteritis among
      children worldwide, annually causes approximately 500,000 deaths among children
      aged <5 years. The primary site of rotavirus infection is the small intestine.
      Pathologic investigations of patients who died of rotavirus infection are limited
      to data from a few reported autopsies, and dehydration with electrolyte imbalance
      is believed to be the major cause of death. Several recent reports suggest that
      children who died during a rotavirus illness were viremic before death, because
      rotavirus was detected at several extraintestinal sites. We report 3 rotavirus
      associated deaths among children, 2 of whom had evidence of rotavirus genome in
      extraintestinal tissues detected by use of novel molecular diagnostic methods.
      The part played by rotavirus in fatal cases is unclear and requires additional
      investigation of diarrhea-associated deaths, because a better understanding might
      alter the approach to treatment and the need for antiviral therapy.

PMID- 14583867
TI  - Pneumonia in older persons.
AB  - Community-acquired pneumonia (CAP) is an important threat to the health of older
      adults. Streptococcus pneumonia remains the most important cause of CAP. Risk
      factors for CAP include alcoholism, asthma, immunosuppression, chronic
      respiratory or cardiac disease, institutionalization, and increasing age.
      Residents of long-term care facilities--a distinct subpopulation of elderly
      people--are at particularly high risk for developing pneumonia. In this setting,
      swallowing difficulties, witnessed aspiration, and receipt of sedatives are
      potentially modifiable risk factors. The clinical presentation in elderly
      patients is characterized by a reduced prevalence of nonrespiratory symptoms. Few
      randomized, controlled trials of therapy exist for elderly persons living in the
      community or in a long-term care setting. Good evidence exists to support the
      annual administration of influenza vaccine to older adults. Although evidence in
      clinical trials differs from evidence in observational studies that demonstrate
      clear benefits associated with the polysaccharide pneumococcal vaccine in this
      population, the vaccine is recommended for adults aged

PMID- 14583868
TI  - Diagnosis and treatment of malaria in children.
AB  - Malaria continues to be a problem for children returning or immigrating to
      industrialized countries from tropical regions. Proper diagnosis begins with
      clinical suspicion. In nonimmune children, malaria typically presents with high
      fever that might be accompanied by chills and headache. Symptoms and signs may be
      more subtle in partially immune children, and anemia and hepatosplenomegaly may
      also be present. Children may present with respiratory distress and/or rapidly
      progressing cerebral malaria that manifests as altered sensorium and, sometimes,
      seizures. Thick blood smears help to determine when infection is present, but a
      single smear without parasites is not sufficient to rule out malaria. Thin blood
      smears aid in identifying the species of parasite. Treatment must include careful
      supportive care, and intensive care measures should be available for treating
      children with complicated Plasmodium falciparum malaria. Medical regimens can
      include mefloquine, atovaquone-proguanil, sulfadoxine-pyrimethamine, quinine or
      quinidine, clindamycin, doxycycline, chloroquine, and primaquine.

PMID- 14583869
TI  - Difficulty swallowing and lack of receipt of highly active antiretroviral therapy
      predict acute weight loss in human immunodeficiency virus disease.
AB  - In human immunodeficiency virus (HIV) disease, symptoms of underlying illness may
      promote weight loss through decreased caloric intake, increased metabolic needs,
      or nutrient malabsorption. We evaluated disease symptoms as predictors of acute
      weight loss (i.e., loss of > or =5% of weight). HIV-infected men and women
      (n=415) were telephoned every 5 weeks to obtain information about weight and
      recent symptoms. Weight change between each pair of consecutive calls (telephone
      intervals, 2814) was calculated. Acute weight loss occurred across 4.5% of
      intervals and among 24% of individuals. Patients reported > or =1 symptom before
      58% of telephone intervals. The most common symptoms or symptom complexes before
      intervals were diarrhea (21% of patients), anorexia (17%), upper respiratory
      symptoms (16%), skin symptoms (12%), and abdominal pain (12%). Trouble swallowing
      (6%) and oral symptoms (7%) were less common. Risk of acute weight loss was
      significantly increased when oral symptoms or trouble swallowing were present,
      and it was decreased when highly active antiretroviral therapy (HAART) was used
      or when diarrhea was not present. Even when HAART is being administered,
      clinicians should remain vigilant regarding weight loss, oral symptoms, and
      trouble swallowing.

PMID- 14583870
TI  - Incident hepatitis C virus in women with human immunodeficiency virus infection.
AB  - Individuals infected with human immunodeficiency virus type 1 (HIV-1) are
      frequently coinfected with hepatitis C virus (HCV). Acute HCV infection is often
      asymptomatic and poorly understood. We conducted a historical prospective study
      of HCV antibody and viremia in plasma samples obtained during 1994-1999 from a
      cohort of initially HIV-1-infected, HCV-uninfected women and from HIV-1-HCV
      uninfected women. Twenty-two (1.5%) of 1517 experienced seroconversion. Of these,
      14 (64%) truly acquired a new infection as assessed by enzyme immunoassay
      response and new-onset viremia. The incidence rate in HIV-1-infected women was
      2.7 cases per 1000 person-years; it was 3.3 cases per 1000 person-years in HIV-1
      seronegative women (relative risk, 1.21; P=.75). Acquisition of HCV was
      associated with any history of drug use (P<.01). Five of 12 viremic,
      seroconverting individuals cleared viremia. Incident HCV infection among HIV-1
      infected and HIV-1-uninfected women was low. It was linked to drug use and
      commonly resolved.

PMID- 14583871
TI  - Mortality risk for patients with cytomegalovirus retinitis and acquired immune
      deficiency syndrome.
AB  - We prospectively followed up 589 patients to evaluate the relationship of anti
      cytomegalovirus (CMV) treatment and immune reconstitution in response to highly
      active antiretroviral therapy (HAART) on the mortality risk of patients with CMV
      retinitis and acquired immune deficiency syndrome. The use of HAART was
      associated with an 81% lower mortality rate (95% confidence interval [CI], 74%
      86%); it was 96% lower (95% CI, 92%-98%) for those who developed immune recovery
      and 49% lower (95% CI, 30-63%) for those who did not. Using time-updated
      multivariate analysis, current systemic anti-CMV treatment was independently
      associated with a 28% lower mortality rate (95% CI, 8%-43%). On the basis of
      these results, for patients who continue to have profound immunodeficiency
      despite HAART, the continued use of HAART and systemic anti-CMV therapy is
      predicted to reduce the risk of mortality by 65%, over and above the benefits of
      Pneumocystis carinii and Mycobacterium avium prophylaxis.

PMID- 14583872
TI  - Use of ultrasonography-assisted liposuction for the treatment of human
      immunodeficiency virus-associated enlargement of the dorsocervical fat pad.
AB  - Enlargement of the dorsocervical fat pad (i.e., "buffalo hump") is one
      manifestation of the lipodystrophy syndrome associated with human
      immunodeficiency virus. We report our experience with the use of ultrasonography
      assisted liposuction in a cohort of 10 patients with this complication.

PMID- 14583873
TI  - The utility of sputum induction for diagnosis of Pneumocystis pneumonia in
      immunocompromised patients without human immunodeficiency virus.
AB  - Sputum induction for the diagnosis of Pneumocystis pneumonia (PCP) is widely used
      for patients with acquired immunodeficiency syndrome (AIDS), but its utility for
      patients with other forms of immunocompromise is less well defined.
      Immunocompromised patients with PCP who do not have human immunodeficiency virus
      (HIV) infection have a lower burden of organisms, and sputum induction may
      consequently have lower diagnostic yield in these patients. However, this
      retrospective review of the experience at a tertiary referral center suggests
      that sputum induction has clinical utility for diagnosing PCP in
      immunocompromised patients without HIV infection.

PMID- 14583874
TI  - Increasing prevalence of methicillin-resistant Staphylococcus aureus infection in
      California jails.
AB  - Staphylococcus aureus clinical isolates obtained from patients who were inmates
      of the San Francisco County jail system showed an increase in the prevalence of
      methicillin-resistant Staphylococcus aureus (MRSA) from 29%, in 1997, to 74%, in
      2002; 91% of the MRSA isolates carried staphylococcal chromosomal cassette mec
      (SCCmec) type IV. Pulsed field gel electrophoresis and multilocus sequence typing
      demonstrated 2 major clonal groups. One of these clonal groups is genetically
      indistinguishable from the strain responsible for an outbreak of MRSA in the Los
      Angeles County jail system in 2002.

PMID- 14583875
TI  - Linezolid-associated toxic optic neuropathy: a report of 2 cases.
AB  - We describe 2 cases in which the prolonged use of linezolid to treat complicated
      methicillin-resistant Staphylococcus aureus infections was followed by acutely
      developed blurred vision and progressive loss of vision and color perception
      during the ensuing few weeks. Both patients received a diagnosis of toxic optic
      neuropathy, and linezolid therapy was stopped. The patients experienced an
      initial rapid partial improvement and a subsequent gradual, almost complete,
      recovery over many months.

PMID- 14583876
TI  - Serum bactericidal activity of the methoxyfluoroquinolones gatifloxacin and
      moxifloxacin against clinical isolates of Staphylococcus species: are the
      susceptibility breakpoints too high?
AB  - Healthy volunteers received a single dose of gatifloxacin and moxifloxacin (400
      mg each), and serum samples were obtained from these volunteers over a 24-h
      period. Prolonged (> or =12 h) serum bactericidal activity (SBA) was observed for
      both agents against staphylococcal isolates with minimum inhibitory
      concentrations (MICs) of gatifloxacin of < or =0.5 mug/mL. In strains with
      gatifloxacin MICs of 1.0 mug/mL, SBA was observed for < or =6 h, and, for
      isolates with gatifloxacin MICs of 2.0 mug/mL, little or no SBA was observed for
      either drug. The relative lack of SBA against less susceptible strains of
      staphylococci suggests that the current susceptibility breakpoint concentration
      (MIC, 2.0 mug/mL) for these methoxyfluoroquinolones against Staphylococcus is too
      high.

PMID- 14583877
TI  - Amphotericin B-related nephrotoxicity has an economic impact on hospitals and
      health systems.

PMID- 14583879
TI  - Human granulocytic ehrlichiosis presenting as acute abdomen in an adult.

PMID- 14583880
TI  - Obstructive sleep apnea due to HIV-associated lipodystrophy.

PMID- 14583881
TI  - Does contact with urine and blood from a rabid dog represent a rabies risk?

PMID- 14583882
TI  - Use of active surveillance cultures to control vancomycin-resistant Enterococcus.

PMID- 14583884
TI  - Why refrigeration paradoxically prolongs bacterial survival in the presence of
      preservatives.

PMID- 14583886
TI  - Fatal type 3 adenoviral pneumonia in immunocompetent adult identical twins.
AB  - We describe adult twin sisters who developed severe adenoviral pneumonia with
      relative leukopenia, progressive focal infiltrates, shock, and hypoxia. Potential
      determinants of severe adenoviral disease are discussed.

PMID- 14583885
TI  - Fatal hemophagocytic lymphohistiocytosis associated with Epstein-Barr virus
      infection in a patient with a novel mutation in the signaling lymphocytic
      activation molecule-associated protein.
AB  - Individuals with X-linked lymphoproliferative disease are susceptible to severe
      Epstein-Barr virus (EBV) infections that are often fatal. Mutations in signaling
      lymphocytic activation molecule-associated protein (SAP) are associated with this
      illness. We describe a patient with a novel serine-to-proline mutation at aa 57
      in SAP and compare the location of the altered amino acid with all known missense
      mutations in the SAP-encoding SH2D1A gene, including those of 4 additional
      individuals whose cases have not been described elsewhere. The patient's genetic
      condition was discovered only after he exhibited an abnormal host response to
      primary EBV infection that resulted in hemophagocytic lymphohistiocytosis
      syndrome, which was complicated by marrow aplasia with terminal disseminated
      aspergillosis.

PMID- 14583888
TI  - Abstracts of the 7th Annual Meeting of the Japanese Heart Failure Society. Osaka,
      Japan, 23-25 October 2003.

PMID- 14583887
TI  - Prophylaxis for ocular toxoplasmosis.
AB  - The protozoan parasite Toxoplasma gondii is an important cause of ocular disease.
      Ocular toxoplasmosis (OT) can be a progressive and recurring disease that can
      threaten visual function. We present 2 cases of recurrent OT in immunocompetent
      patients for whom prophylaxis prevented recurrence of disease.

PMID- 14583889
TI  - Nitric oxide and vascular reactivity in African American patients with
      hypertension.

PMID- 14583891
TI  - Heart failure in African Americans: pathophysiology and treatment.

PMID- 14583893
TI  - The dilemma of drug development for heart failure: when is the time to initiate
      large clinical trials?

PMID- 14583892
TI  - The African-American Heart Failure Trial (A-HeFT): rationale and methodology.

PMID- 14583894
TI  - Ventricular remodeling in heart failure: a credible surrogate endpoint.

PMID- 14583895
TI  - A comparative analysis of the results from 4 trials of beta-blocker therapy for
      heart failure: BEST, CIBIS-II, MERIT-HF, and COPERNICUS.
AB  - BACKGROUND: Recent large randomized, controlled trials (BEST [Beta-blocker
      Evaluation of Survival Trial], CIBIS-II [Cardiac Insufficiency Bisoprolol Trial
      II], COPERNICUS [Carvedilol Prospective Randomized Cumulative Survival Study],
      and MERIT-HF [Metoprolol Randomized Intervention Trial in Congestive Heart
      Failure]) have addressed the usefulness of beta-blockade in the treatment of
      advanced heart failure. CIBIS-II, COPERNICUS, and MERIT-HF have shown that beta
      blocker treatment with bisoprolol, carvedilol, and metoprolol XL, respectively,
      reduce mortality in advanced heart failure patients, whereas BEST found a
      statistically nonsignificant trend toward reduced mortality with bucindolol. We
      conducted a post hoc analysis to determine whether the response to beta-blockade
      in BEST could be related to differences in the clinical and demographic
      characteristics of the study populations. We generated a sample from BEST to
      resemble the patient cohorts studied in CIBIS-II and MERIT-HF to find out whether
      the response to beta-blocker therapy was similar to that reported in the other
      trials. These findings are further compared with COPERNICUS, which entered
      patients with more severe heart failure. METHODS: To achieve conformity with the
      entry criteria for CIBIS-II and MERIT-HF, the BEST study population was adjusted
      to exclude patients with systolic blood pressure <100 mm Hg, heart rate <60 bpm,
      and age >80 years (exclusion criteria employed in those trials). The BEST
      comparison subgroup (BCG) was further modified to more closely reflect the racial
      demographics reported for patients enrolled in CIBIS-II and MERIT-HF. The
      association of beta-blocker therapy with overall survival and survival free of
      cardiac death, sudden cardiac death, and progressive pump failure in the BCG was
      assessed. RESULTS: In the BCG subgroup, bucindolol treatment was associated with
      significantly lower risk of death from all causes (hazard ratio (HR)=0.77 [95%
      CI=0.65, 0.92]), cardiovascular death (HR=0.71 [0.58, 0.86]), sudden death
      (HR=0.77 [0.59, 0.999]), and pump failure death (HR=0.64 [0.45, 0.91]).
      CONCLUSIONS: Although not excluding the possibility of differences resulting from
      chance alone or to different properties among beta-blockers, this study suggests
      the possibility that different heart failure population subgroups may have
      different responses to beta-blocker therapy.

PMID- 14583896
TI  - Why do phase III trials of promising heart failure drugs often fail? The
      contribution of "regression to the truth".
AB  - There has been considerable recent disappointment with the failure of a number of
      major new pharmacological strategies for the treatment of chronic heart failure.
      In turn, there has been much speculation as to why trials of these therapies have
      not shown benefit. Among a number of plausible and scientifically valid reasons,
      consideration should be afforded to the potential contribution of "regression to
      the truth." Regression to the truth derives from the biological concept of
      regression to the mean, whereby random fluctuations in a biological variable
      occur over time, such that the true value of the variable is approached with
      repeated measurements. This same concept can be applied to clinical trial
      programs for new drugs for heart failure. Because only strongly positive trials
      generally go on to phase III testing, and some of these early phase studies are
      positive by chance alone, on retesting in phase III the results are very likely
      not be as strongly positive. Numerous examples of regression to the truth apply
      for trials of heart failure therapies, as well as in other areas. A major concern
      is how to minimize negative outcomes in phase III trials. One approach is to
      perform major rigorous phase II testing. Alternatively, avoidance of phase II
      testing will minimize "regression to the truth" because there are no data in
      phase II from which regression might occur. However, this approach does not
      obviate the need for an evaluation process in the selection of candidate agents
      (and their appropriate dose) in order to proceed to definitive testing.

PMID- 14583897
TI  - Meta-analysis of the effects of endothelin receptor blockade on survival in
      experimental heart failure.
AB  - BACKGROUND: Although an initial study of endothelin receptor blockade reported
      positive findings, subsequent experiments and clinical trials in humans found
      little or no benefit. METHODS: We applied meta-analytic methods to assess the
      methodologic rigor of preclinical studies of endothelin blockade and to
      quantitatively evaluate the totality of evidence regarding the effect of
      endothelin receptor blockers in experimental heart failure. A total of 396
      animals were assigned to control and 594 were assigned to experimental therapy in
      the pooled analysis. Of the 9 studies identified, no study reported a priori
      sample size justification. Although there was a tendency to increased mortality
      with early administration (relative risk 1.39, P=.15) and decreased mortality
      with late administration (relative risk 0.85, P=.6), in the overall analysis,
      there was no significant evidence of benefit or harm (relative risk 1.03, P=.9).
      Studies with a small sample size had estimated effects that tended to deviate
      further from the pooled estimate of all studies. CONCLUSIONS: Consideration of
      mortality effects in the totality of studies revealed no significant effect of
      endothelin antagonists in animal models of experimental heart failure. Given the
      potential for between-study variability, reliance on studies with small sample
      size may lead to unrealistic expectations when extrapolating preclinical
      experimental results to future research.

PMID- 14583898
TI  - The use of implantable cardioverter-defibrillators in pediatric patients awaiting
      heart transplantation.
AB  - BACKGROUND: This multicenter study evaluated experience with implantable
      cardioverter defibrillators (ICD) as a bridge to orthotopic heart transplantation
      (OHT) in children. METHODS: The application of ICD therapy continues to expand in
      pediatric populations, due in part to improved technology and new indications,
      including the prevention of sudden death while awaiting OHT. METHODS: We
      performed a retrospective review of ICD databases at 9 pediatric transplant
      centers. RESULTS: Twenty-eight patients (16 males) underwent implantation or had
      a preexisting ICD while awaiting OHT between 1990 and 2002. The median age at
      implant was 14.3 years (11 months to 21 years) with a median weight of 49 kg
      (11.7-88 kg). Diagnoses included cardiomyopathy (n=22), and congenital heart
      disease (n=6). Indications for ICD implantation included ventricular
      tachycardia/fibrillation (n=23), syncope (n=5), aborted sudden death with no
      documentation of rhythm disturbance (n=5), ventricular ectopy (n=1), and poor
      function (n=5). Of the 28 ICDs, 23 were implanted by a transvenous approach and 5
      by epicardial route. There were 55 defibrillator discharges in 17 patients, 47
      (85%) of which (in 13 patients) were appropriate. The 8 inappropriate discharges
      (in 6 patients) were triggered by sinus tachycardia, inappropriate sensing, and
      atrial flutter. The mean time from implantation to first appropriate shock was
      6.9 months (1 day to 2.6 years). Twenty-one patients underwent transplantation
      during the study period, whereas 2 died while awaiting a donor. Morbidity
      included a lead fracture, 3 episodes of electromechanical dissociation, and 1
      episode of electrical storm. CONCLUSIONS: ICD implantation represents an
      effective bridge to transplantation in pediatric patients. The complication rate
      is low, with inappropriate device discharge due primarily to sinus tachycardia or
      atrial flutter. There is a high incidence of appropriate ICD therapy for
      malignant ventricular arrhythmias in this highly selected group of patients.

PMID- 14583899
TI  - Dobutamine potentiates the peripheral chemoreflex in patients with congestive
      heart failure.
AB  - BACKGROUND: beta-Adrenergic agonists may increase chemoreflex sensitivity to
      hypoxia in normal humans. Chemoreflex function is important in the
      pathophysiology of heart failure. Whether the beta-1 agonist dobutamine, which is
      frequently administered to patients with heart failure, alters their chemoreflex
      sensitivity is not known. METHODS: We tested the hypothesis that dobutamine
      increases chemoreflex sensitivity in patients with congestive heart failure (CHF)
      using a randomized, double-blinded, placebo-controlled study design. We assessed
      the influence of dobutamine on minute ventilation and hemodynamics during
      normoxic breathing and during peripheral chemoreflex deactivation by hyperoxia
      (100% O(2)) in 9 patients with CHF. RESULTS: Dobutamine increased minute
      ventilation in patients with CHF (9.4+/-0.9 versus 8.4+/-0.7 L/min, P=.005)
      during normoxia. Peripheral chemoreflex deactivation by hyperoxia suppressed the
      ventilatory effects of dobutamine (10.4+/-1.4 L/min for dobutamine versus 10.0+/
      1.2 L/min for placebo, P=.34). CONCLUSIONS: Dobutamine increases ventilation
      during normoxia, but not during hyperoxia in patients with CHF. We conclude that
      dobutamine enhances peripheral chemoreflex sensitivity in patients with
      congestive heart failure.

PMID- 14583900
TI  - Sympathetic nervous system function as measured by I-123 metaiodobenzylguanidine
      predicts transplant-free survival in heart failure patients with idiopathic
      dilated cardiomyopathy.
AB  - BACKGROUND: Heightened activity of the sympathetic nervous system in heart
      failure patients is a major contributor to disease progression and death. I-123
      metaiodobenzylguanidine (MIBG) provides an accurate, noninvasive method to assess
      cardiac sympathetic nerve activity. METHODS: Thirty-seven patients with New York
      Heart Association class II, III, or IV heart failure underwent baseline
      measurement of I-123 MIBG heart-to-mediastinum ratios, maximum oxygen
      consumption, radionuclide left ventricular ejection fraction, and plasma
      norepinephrine levels. Patients were followed 48.8+/-8.6 months to endpoints of
      cardiac death or transplantation. The heart-to-mediastinum ratio of I-123 MIBG
      activity measured 15 minutes after injection was the only independent predictor
      of transplant-free survival (P<.0001). I-123 MIBG imaging at 15 minutes
      identified patients with subsequent cardiac transplantation or death with a
      sensitivity of 92% and specificity of 72%, whereas the corresponding values for
      maximum oxygen consumption were 75% and 56%. By Kaplan-Meier survival analysis,
      the time to a cardiac endpoint was significantly shorter in patients with a 15
      minute I-123 MIBG heart-to-mediastinum ratio below the group mean ratio of 1.536,
      compared with patients with a preserved I-123 MIBG ratio. Maximum oxygen
      consumption was not predictive of time to cardiac transplant or death.
      CONCLUSIONS: In this study of patients with congestive heart failure resulting
      from dilated cardiomyopathy, a 15-minute heart-to-mediastinum ratio of I-123 MIBG
      activity provided more accurate prediction of cardiac transplantation or death
      than other standard clinical tests.

PMID- 14583901
TI  - Instantaneous assessment of left ventricular midwall mechanics with tissue
      Doppler tracking technique.
AB  - BACKGROUND: Left ventricular (LV) systolic function is better characterized by
      midwall mechanics in patients with LV hypertrophy than by endocardial LV
      function, and the midwall mechanics is an independent predictor of prognosis.
      However, a complex calculation is currently required to assess it, and it is not
      routinely assessable in clinical practice. Tissue Doppler imaging enables
      tracking of a point within the LV wall though a cardiac cycle; we tested our
      hypothesis that the tissue Doppler tracking technique provides an instantaneous
      and reliable evaluation of midwall mechanics. METHODS: LV M-mode echocardiogram
      was recorded in 18 subjects with conventional echocardiography and with tissue
      Doppler imaging. The midwall shortening was calculated from the data obtained
      with conventional echocardiography for the comparison with that measured with the
      tissue Doppler tracking technique. The tissue Doppler-determined midwall
      shortening correlated well with conventionally calculated value (r=.84, P<.0001),
      and their difference was small irrespective of absolute value of the midwall
      shortening. CONCLUSIONS: The midwall mechanics can be instantaneously and
      accurately evaluated with the tissue Doppler tracking technique.

PMID- 14583902
TI  - Beta-blockers are effective in congestive heart failure patients with atrial
      fibrillation.
AB  - BACKGROUND: It is controversial whether or not beta-blockers are effective in
      patients with congestive heart failure (CHF) who are complicated by persistent
      atrial fibrillation (AF). METHODS: We attempted to determine the potential
      differences in the efficacy between atrial fibrillation and sinus rhythm in 70
      CHF patients with NYHA class II-IV and radionuclide ejection fraction (LVEF) <40%
      who received metoprolol or carvedilol over 16 weeks. RESULTS: Left ventricular
      end-diastolic dimension was decreased in AF group (n=24) 4 weeks (early) and 16
      to 48 weeks (late) after introduction of beta-blockers (P<.05, P<.001), but not
      in the sinus rhythm (NSR) group (n=46). End-systolic dimension was decreased in
      both the AF group (P<.01, P<.0001) and the NSR group (P<.01, P<.0001). LVEF was
      increased in both the AF group (P<.0005, P<.0001) and the NSR group (P<.0001,
      P<.0001) early and late after the therapy. Increase in LVEF by the therapy tended
      to be higher in the AF group than in the NSR group (P=.056). Plasma brain
      natriuretic peptide level did not change significantly throughout the observation
      period, although the level tended to be lowered in the AF group late after
      introduction of beta-blockers (P=.093). CONCLUSIONS: Because beta-blockers are
      effective in both NSR and AF patients with CHF, such a mode of therapy should be
      recommended in patients with AF.

PMID- 14583903
TI  - Effect of a pharmacist-led intervention on diuretic compliance in heart failure
      patients: a randomized controlled study.
AB  - BACKGROUND: Noncompliance is a major factor in the morbidity and unnecessary
      hospital readmissions for patients with heart failure. Several studies have aimed
      to reduce rehospitalizations in heart failure patients through a comprehensive,
      multidisciplinary approach. Medication compliance was rarely measured in these
      studies or, when it was measured, the method employed was seldom valid. We aimed
      at determining the effect of a pharmacist-led intervention on medication
      compliance in patients with heart failure. METHODS: We conducted a randomized
      controlled trial into the effect of a pharmacist-led intervention on medication
      compliance in patients with heart failure (predominantly New York Heart
      Association [NYHA] II and III) treated with loop diuretics, presenting to a
      cardiology outpatient clinic or admitted to hospitals in The Netherlands.
      Patients in the intervention group received monthly consultations from their
      community pharmacist during a 6-month period. Patients in the control group
      received usual care. Primary endpoint was medication compliance, assessed with a
      medication event monitoring system, an electronic pill bottle that registers time
      of opening. Secondary endpoints were the number of rehospitalizations, death, and
      quality of life. RESULTS: A total of 152 patients were randomized: 74 patients to
      the intervention arm and 78 patients to the usual care arm. Over the 6-month
      study period, patients in the intervention group had 140/7656 days without use of
      loop diuretics compared with 337/6196 days in the usual care group (relative risk
      0.33 [confidence interval (CI) 95% 0.24-0.38]). Two consecutive days of nondosing
      occurred on 18/7656 days in the intervention group compared with 46/6196 days in
      the usual care group (relative risk 0.32 [CI 95% 0.19-0.55]). There were no
      significant differences in rehospitalizations, mortality, or disease-specific
      quality of life between groups. CONCLUSIONS: A pharmacy-led intervention can
      improve medication compliance in patients with moderate to severe heart failure,
      even in those with relatively high compliance. Future interventions should also
      focus at less compliant patients.

PMID- 14583904
TI  - Apparent protective effect of increased left ventricular wall thickness in an ICD
      population.
AB  - BACKGROUND: Expanding indications for the implantable cardioverter defibrillator
      (ICD) call for further enhancement of patient selection for optimization of use.
      Because a subgroup of patients who receive ICDs may not receive therapies, we
      sought to identify clinical predictors of therapy-free survival in ICD patients.
      METHODS: We performed an analysis of a single-center, 13-year ICD implantation
      experience (1990-2002). The association between therapy-free survival and several
      clinical variables was evaluated. RESULTS: From a total of 562 patients included
      in the database, 98 patients (17%) received no shock therapies or antitachycardia
      pacing (group A). When compared with a randomly selected sample of 131 patients
      who did receive ICD therapies (group B), there were no significant differences in
      age, gender, frequency of coronary artery disease, or extent of left ventricular
      (LV) dysfunction. However, left ventricular hypertrophy (LVH; increased wall
      thickness by echocardiography) was significantly more common in group A versus
      group B (30% versus 18%; Pearson's chi-square=4.69, P=.03). The odds of patients
      in group A having LVH were 1.98 times higher versus group B (95% confidence
      interval for odds ratio: 1.06-3.71). Comparisons of calculated mean LV mass
      between the 2 groups were not significantly different (group A 283+/-112 gm
      versus group B 271+/-108, P=.58). The overall mortality rate was 17% in group A
      and 22% in group B (P=.29). CONCLUSIONS: Increased LV wall thickness was a
      significant, independent predictor of therapy-free survival in this ICD
      population. Because LV mass was unchanged, this finding may reflect the
      importance of LV dilation and wall thinning (ie, eccentric remodeling) as a risk
      factor for recurrent ventricular arrhythmia in ICD patients.

PMID- 14583905
TI  - BNP as discharge criteria for heart failure.
AB  - BACKGROUND: Heart failure (HF) is a significant clinical and economic burden in
      the industrialized world. Advances in pharmaceutical compounds and various
      medical device technologies along with the use of sophisticated HF clinics have
      enhanced HF treatment and improved morbidity, mortality, and quality of life.
      However, hospital readmission rates remain stubbornly high. B-type natriuretic
      peptide (BNP) levels provide valuable information about a patient's chance of
      readmission within 30 days of discharge, making BNP a potentially useful tool for
      making discharge decisions and possibly reducing readmissions. METHODS: This
      review examines the strength and level of evidence in key areas to determine if
      BNP levels could be used as a guide for discharge of HF patients. Although most
      of the literature describes nonrandomized studies, there is general agreement
      that BNP levels can be measured accurately and precisely, that BNP levels reflect
      varying physiologic states, and that they predict outcomes. CONCLUSIONS: More
      studies are needed to determine extent of biologic variability. The further use
      of BNP as a potential discharge marker is promising but awaits additional
      randomized study that reflects use in a broad-based population.

PMID- 14583906
TI  - Effect of valsartan on hospitalization in Val-HeFT.

PMID- 14583907
TI  - Energy and protein intake in pregnancy.
AB  - BACKGROUND: Gestational weight gain is positively associated with fetal growth,
      and observational studies of food supplementation in pregnancy have reported
      increases in gestational weight gain and fetal growth. OBJECTIVES: To assess the
      effects of advice to increase or reduce energy or protein intake, or of actual
      energy or protein supplementation or restriction, during pregnancy on energy and
      protein intakes, gestational weight gain, and the outcome of pregnancy. SEARCH
      STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register
      (October 2002) and contacted researchers in the field. SELECTION CRITERIA:
      Acceptably controlled trials of dietary advice to increase or reduce energy or
      protein intake, or of actual energy or protein supplementation or restriction,
      during pregnancy. DATA COLLECTION AND ANALYSIS: Data were extracted by the
      authors from published reports, and supplemented by additional information from
      trialists contacted by the authors. MAIN RESULTS: In five trials involving 1134
      women, nutritional advice to increase energy and protein intakes was successful
      in achieving those goals, but no consistent benefit was observed on pregnancy
      outcomes. In 13 trials involving 4665 women, balanced energy/protein
      supplementation was associated with modest increases in maternal weight gain and
      in mean birth weight, and a substantial reduction in risk of small-for
      gestational-age (SGA) birth. These effects did not appear greater in
      undernourished women. No significant effects were detected on preterm birth, but
      significantly reduced risks were observed for stillbirth and neonatal death. In
      two trials involving 1076 women, high-protein supplementation was associated with
      a small, nonsignificant increase in maternal weight gain but a nonsignificant
      reduction in mean birthweight, a significantly increased risk of SGA birth, and a
      nonsignificantly increased risk of neonatal death. In 3 trials involving 966
      women, isocaloric protein supplementation was also associated with an increased
      risk of SGA birth. In three trials involving 384 women, energy/protein
      restriction of pregnant women who were overweight or exhibited high weight gain
      significantly reduced weekly maternal weight gain and mean birth weight but had
      no effect on pregnancy-induced hypertension or pre-eclampsia. REVIEWER'S
      CONCLUSIONS: Dietary advice appears effective in increasing pregnant women's
      energy and protein intakes but is unlikely to confer major benefits on infant or
      maternal health. Balanced energy/protein supplementation improves fetal growth
      and may reduce the risk of fetal and neonatal death. High-protein or balanced
      protein supplementation alone is not beneficial and may be harmful to the
      infant.Protein/energy restriction of pregnant women who are overweight or exhibit
      high weight gain is unlikely to be beneficial and may be harmful to the infant.

PMID- 14583908
TI  - Family intervention for schizophrenia.
AB  - BACKGROUND: It has been found that people with schizophrenia from families that
      express high levels of criticism, hostility, or over involvement, have more
      frequent relapses than people with similar problems from families that tend to be
      less expressive of their emotions. Psychosocial interventions designed to reduce
      these levels of expressed emotions within families now exist. These interventions
      are proposed as adjuncts rather than alternatives to drug treatments and their
      main purpose is to decrease the stress within the family and also the rate of
      relapse. OBJECTIVES: To estimate the effects of family psychosocial interventions
      in community settings for the care of those with schizophrenia or schizophrenia
      like conditions compared to standard care. SEARCH STRATEGY: We updated previous
      searches of the Cochrane Schizophrenia Group Register (June 1998), MEDLINE (1966
      1995), the Cochrane Library (Issue 2 1998), EMBASE (1981-1995) and MEDLINE (1966
      1995) by searching Cochrane Schizophrenia Group Register (November 2002).
      References of all identified studies were searched for further trial citations
      and authors of trials were contacted. SELECTION CRITERIA: Randomised or quasi
      randomised studies were selected if they focused primarily on families of people
      with schizophrenia or schizoaffective disorder and compared community-orientated
      family-based psychosocial intervention of more than five sessions with standard
      care. DATA COLLECTION AND ANALYSIS: Data were reliably extracted, and, where
      appropriate and possible, summated. Relative risk (RR) with 95% confidence
      intervals (CI) and number needed to treat (NNT) were estimated. The reviewers
      assume that people who died or dropped out had no improvement and tested the
      sensitivity of the final results to this assumption. MAIN RESULTS: Family
      intervention may decrease the frequency of relapse (n=721, 14 RCTs, RR 0.72 CI
      0.6 to 0.9, NNT 7 CI 5 to 16). These data are statistically heterogeneous, the
      trend over time of this finding is towards the null and some small but negative
      studies may not have been identified by the search. Family intervention may also
      encourage compliance with medication (n=369, 7 RCTs, RR 0.74 CI 0.6 to 0.9, NNT 7
      CI 4 to 19) but does not obviously affect the tendency of individuals/families to
      drop out of care (n=327, 4 RCTs, RR attrition at 3 months 0.86 CI 0.3 to 2.1). It
      may improve general social impairment and the levels of expressed emotion within
      the family. This review provides no data to suggest that family intervention
      either prevents or promotes suicide. REVIEWER'S CONCLUSIONS: Clinicians,
      researchers, policy makers and recipients of care cannot be confident of the
      effects of family intervention from the findings of this review. Further data
      from already completed trials could greatly inform practice and more trials are
      justified as long as their participants, interventions and outcomes are
      applicable to routine care.

PMID- 14583909
TI  - Elective high frequency oscillatory ventilation versus conventional ventilation
      for acute pulmonary dysfunction in preterm infants.
AB  - BACKGROUND: Respiratory failure due to lung immaturity is a major cause of
      mortality in preterm infants. Although intermittent positive pressure ventilation
      (IPPV) saves lives, lung distortion during its use is associated with lung injury
      and chronic lung disease (CLD). Conventional IPPV is provided at 30-80 breaths
      per minute while a newer form of ventilation called high frequency oscillatory
      ventilation (HFOV) provides 'breaths' at 10-15 cycles per second. This has been
      shown to result in less lung injury in experimental studies. OBJECTIVES: The
      objective of this review is to determine whether the elective use of high
      frequency oscillatory ventilation as compared to conventional ventilation (CV) in
      preterm infants who are mechanically ventilated for the respiratory distress
      syndrome decreases the incidence of chronic lung disease, without adverse
      effects. SEARCH STRATEGY: Searches were made of the Oxford Database of Perinatal
      Trials, MEDLINE, EMBASE, previous reviews including cross references, abstracts,
      conferences and symposia proceedings, expert informants, journal hand searching
      by the Cochrane Collaboration, mainly in the English language. The search was
      updated in May 2003. SELECTION CRITERIA: Randomized controlled trials comparing
      HFOV and CV in preterm or low birth weight infants with pulmonary dysfunction,
      mainly due to RDS, who are to be given IPPV. Randomization and commencement of
      treatment should have been as soon as possible after the start of IPPV and
      usually in the first 12 hours of life. DATA COLLECTION AND ANALYSIS: The
      methodological quality of each trial was independently reviewed by the various
      authors. Each author extracted data separately; they were compared and
      differences were resolved. Treatment effects were expressed using relative risk
      (RR) and risk difference (RD). From 1/RD the number needed to treat (NNT) to
      produce one outcome were calculated. Ninety five percent confidence intervals
      were used for all measures of effect. MAIN RESULTS: Eleven eligible studies on
      3,275 infants were included. Meta-analysis comparing HFOV with CV revealed no
      evidence of effect on mortality at 28-30 days of age or at approximately term
      equivalent age. These results were consistent across studies. The effect of HFOV
      on CLD in survivors at term equivalent GA was inconsistent across studies and not
      significant overall. Pre-specified subgroup analyses according to use of a high
      volume strategy, or use of surfactant, did not identify subgroups in which there
      was evidence of effect on death, or in which the size of effect on CLD was
      substantially increased, or in which heterogeneity of treatment effect on CLD was
      removed. Short term neurological morbidity caused by HFOV was found in some
      studies, but this effect was not statistically significant overall. The subgroup
      of two trials not using a high volume strategy with HFOV found increased rates of
      Grade 3 or 4 IVH and of periventricular leukomalacia. An adverse effect of HFOV
      on longer term neurodevelopment was found in one large trial but not in two other
      small trials which reported this outcome. REVIEWER'S CONCLUSIONS: There is no
      clear evidence from this systematic review that elective HFOV, as compared with
      CV, offers important advantages when used as the initial ventilation strategy to
      treat preterm babies with acute pulmonary dysfunction. There is no evidence of a
      reduction in death rate. There may be a small reduction in the rate of CLD with
      HFOV use but the evidence is weakened by the inconsistency of this effect across
      trials and is not significant overall. Adverse effects on short term neurological
      outcomes have been observed in some studies but these effects are not significant
      overall. Information about effects on long term outcome is not adequate overall.
      Any future trials on elective HFOV should target those infants who are at most
      risk of CLD (extremely preterm), compare different strategies for generating HFOV
      and CV, and report important long term pulmonary and neurodevelopmental outcomes.
      Economic analysis should also be incorporated.

PMID- 14583910
TI  - Magnesium sulphate versus diazepam for eclampsia.
AB  - BACKGROUND: Eclampsia, the occurrence of a convulsion in association with pre
      eclampsia, remains a rare but serious complication of pregnancy. A number of
      different anticonvulsants are used to control eclamptic fits and to prevent
      further fits. OBJECTIVES: The objective of this review was to assess the effects
      of magnesium sulphate compared with diazepam when used for the care of women with
      eclampsia. Magnesium sulphate is compared with phenytoin and with lytic cocktail
      in other Cochrane reviews. SEARCH STRATEGY: We searched the Cochrane Pregnancy
      and Childbirth trials register (28 November 2002) and the Cochrane Central
      Register of Controlled Trials (The Cochrane Library, Issue 4, 2002). SELECTION
      CRITERIA: Randomised trials comparing magnesium sulphate (intravenous or
      intramuscular administration) with diazepam for women with a clinical diagnosis
      of eclampsia. DATA COLLECTION AND ANALYSIS: Both reviewers assessed and extracted
      data. MAIN RESULTS: Seven trials involving 1441 women are included. Most of the
      data are from trials of good quality. Magnesium sulphate is associated with a
      reduction in maternal death when compared to diazepam (six trials 1336 women;
      relative risk (RR) 0.59, 95% confidence interval (CI) 0.37 to 0.94). There is
      also a substantial reduction in the risk recurrence of further fits (seven trials
      1441 women; RR 0.44, 95% CI 0.34 to 0.57). There were few differences in any
      other measures of outcome, except for fewer Apgar scores less than seven at five
      minutes (two trials 597 babies; RR 0.72, 95% CI 0.55 to 0.94) and fewer babies
      with a length of stay in special care baby unit more than seven days (three
      trials 631 babies; RR 0.66, 95% CI 0.46 to 0.95) associated with magnesium
      sulphate. REVIEWER'S CONCLUSIONS: Magnesium sulphate appears to be substantially
      more effective than diazepam for treatment of eclampsia.

PMID- 14583911
TI  - Magnesium sulphate versus phenytoin for eclampsia.
AB  - BACKGROUND: Eclampsia, the occurrence of a convulsion (fit) in association with
      pre-eclampsia, remains a rare but serious complication of pregnancy. A number of
      different anticonvulsants are used to control eclamptic fits and to prevent
      further convulsions. OBJECTIVES: The objective of this review was to assess the
      effects of magnesium sulphate compared with phenytoin when used for the care of
      women with eclampsia. Magnesium sulphate is compared with diazepam and with lytic
      cocktail in other Cochrane reviews. SEARCH STRATEGY: We searched the Cochrane
      Pregnancy and Childbirth trials register (28 November 2002) and the Cochrane
      Central Register of Controlled Trials (The Cochrane Library, Issue 4, 2002).
      SELECTION CRITERIA: Randomised trials comparing magnesium sulphate (intravenous
      or intramuscular administration) with phenytoin for women with a clinical
      diagnosis of eclampsia. DATA COLLECTION AND ANALYSIS: Both reviewers assessed
      trial quality and extracted data. MAIN RESULTS: Six trials involving 897 women
      are included. Most of the data are from trials of good quality. Magnesium
      sulphate is associated with a substantial reduction in the recurrence of
      convulsions, when compared to phenytoin (five trials, 895 women; relative risk
      (RR) 0.31, 95% confidence interval (CI) 0.20 to 0.47). The trend in maternal
      mortality favours magnesium sulphate, but this difference is not statistically
      significant (two trials, 797 women; RR 0.50, 95% CI 0.24 to 1.05). There are also
      reductions in the risk of pneumonia (RR 0.44, 95% CI 0.24 to 0.79), ventilation
      (RR 0.66, 95% CI 0.49 to 0.90) and admission to an intensive care unit (RR 0.67,
      95% CI 0.50 to 0.89) associated with the use of magnesium sulphate. For the baby,
      magnesium sulphate was associated with fewer admissions to a special care baby
      unit (SCBU) (one trial, 518 babies; RR 0.73, 95% CI 0.58 to 0.91) and fewer
      babies who died or were in SCBU for more than seven days (one trial, 665 babies;
      RR 0.77, 95% CI 0.63 to 0.95). REVIEWER'S CONCLUSIONS: Magnesium sulphate appears
      to be substantially more effective than phenytoin for treatment of eclampsia.

PMID- 14583912
TI  - Maternal dietary antigen avoidance during pregnancy and/or lactation for
      preventing or treating atopic disease in the child.
AB  - BACKGROUND: Some breastfed infants with atopic eczema benefit from elimination of
      cow milk, egg, or other antigens from their mother's diet. Maternal dietary
      antigens are also known to cross the placenta. OBJECTIVES: To assess the effects
      of prescribing an antigen avoidance diet during pregnancy and/or lactation on
      maternal and infant nutrition and on the prevention or treatment of atopic
      disease in the child. SEARCH STRATEGY: We searched the Cochrane Pregnancy and
      Childbirth Group trials register (October 2002) and contacted researchers in the
      field. SELECTION CRITERIA: All randomized or quasi-randomized comparisons of
      maternal dietary antigen avoidance prescribed to pregnant or lactating women. We
      excluded trials of multimodal interventions that included manipulation of the
      infant's diet other than breast milk or of nondietary aspects of the infant's
      environment. DATA COLLECTION AND ANALYSIS: We extracted data from published
      reports, supplemented by additional information received from the trialists we
      contacted. MAIN RESULTS: The evidence from 4 trials involving approximately 451
      participants does not suggest a protective effect of maternal dietary antigen
      avoidance during pregnancy on the incidence of atopic eczema during the first 12
      to 18 months of life. Data on allergic rhinitis/conjunctivitis and urticaria are
      limited to a single trial each and are insufficient to draw meaningful
      inferences. Longer-term atopic outcomes have not been reported. The restricted
      diet during pregnancy was associated with a slightly but statistically
      significantly lower mean gestational weight gain, a nonsignificantly higher risk
      of preterm birth, and a nonsignificant reduction in mean birthweight.The evidence
      from 3 trials involving approximately 210 participants suggests a protective
      effect of maternal antigen avoidance during lactation on the incidence and
      severity of atopic eczema during the first 12 to 18 months, but methodologic
      shortcomings argue for caution in interpretation.One crossover trial involving 17
      lactating mothers of infants with established atopic eczema found that maternal
      dietary antigen avoidance was associated with a nonsignificant reduction in
      eczema severity. REVIEWER'S CONCLUSIONS: Prescription of an antigen avoidance
      diet to a high-risk woman during pregnancy is unlikely to reduce substantially
      her child's risk of atopic diseases, and such a diet may adversely affect
      maternal and/or fetal nutrition. Prescription of an antigen avoidance diet to a
      high-risk woman during lactation may reduce her child's risk of developing atopic
      eczema, but better trials are needed. Dietary antigen avoidance by lactating
      mothers of infants with atopic eczema may reduce the severity of the eczema, but
      larger trials are needed.

PMID- 14583913
TI  - Maternal oxygen administration for fetal distress.
AB  - BACKGROUND: Maternal oxygen administration has been used in an attempt to lessen
      fetal distress by increasing the available oxygen from the mother. This has been
      used for suspected fetal distress during labour, and prophylactically during the
      second stage of labour on the assumption that the second stage is a time of high
      risk for fetal distress. OBJECTIVES: The objective of this review was to assess
      the effects of maternal oxygenation for fetal distress during labour and to
      assess the effects of prophylactic oxygen therapy during the second stage of
      labour on perinatal outcome. SEARCH STRATEGY: We searched the Cochrane Pregnancy
      and Childbirth Group trials register (March 2003) and the Cochrane Central
      Register of Controlled Trials (The Cochrane Library, Issue 3, 2002). SELECTION
      CRITERIA: Randomised trials comparing maternal oxygen administration for fetal
      distress during labour and prophylactic oxygen administration during the second
      stage of labour with a control group (dummy or no oxygen therapy). DATA
      COLLECTION AND ANALYSIS: Both reviewers assessed eligibility and trial quality.
      Data were extracted, checked and entered into RevMan software. For dichotomous
      data, relative risks (RR) and 95% confidence intervals (CI) were calculated. For
      continuous data, weighted mean differences and 95% CI were calculated. MAIN
      RESULTS: No trials addressing maternal oxygen therapy for fetal distress were
      located. Two trials which addressed prophylactic oxygen administration during
      labour were included. Abnormal cord blood pH values (less than 7.2) were recorded
      significantly more frequently in the oxygenation group than the control group
      (relative risk 3.51, 95% confidence interval 1.34 to 9.19). There were no other
      statistically significant differences between the groups. There were conflicting
      conclusions on the effect of the duration of oxygen administration on umbilical
      artery pH values between the two trials. REVIEWER'S CONCLUSIONS: Implications for
      practiceThere is not enough evidence to support the use of prophylactic oxygen
      therapy for women in labour, nor to evaluate its effectiveness for fetal
      distress. Implications for researchIn view of the widespread use of oxygen
      administration during labour and the possibility that it may be ineffective or
      harmful, there is an urgent need for randomised trials to assess its effects.

PMID- 14583914
TI  - Interventions for nausea and vomiting in early pregnancy.
AB  - BACKGROUND: Nausea and vomiting are the most common symptoms experienced in early
      pregnancy, with nausea affecting between 70 and 85% of women. About half of
      pregnant women experience vomiting. OBJECTIVES: To assess the effects of
      different methods of treating nausea and vomiting in early pregnancy. SEARCH
      STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register
      (December 2002) and the Cochrane Central Register of Controlled Trials (The
      Cochrane Library, Issue 4, 2002). SELECTION CRITERIA: Randomised trials of any
      treatment for nausea and/or vomiting in early pregnancy. DATA COLLECTION AND
      ANALYSIS: Two reviewers assessed the trial quality and extracted the data
      independently. MAIN RESULTS: Twenty-eight trials met the inclusion criteria. For
      milder degrees of nausea and vomiting, 21 trials were included. These trials were
      of variable quality. Nausea treatments were: different antihistamine medications,
      vitamin B6 (pyridoxine), the combination tablet Debendox (Bendectin), P6
      acupressure and ginger. For hyperemesis gravidarum, seven trials were identified
      testing treatments with oral ginger root extract, oral or injected
      corticosteroids or injected adrenocorticotropic hormone (ACTH), intravenous
      diazepam and acupuncture. Based on 12 trials, there was an overall reduction in
      nausea from anti-emetic medication (odds ratio 0.16, 95% confidence interval 0.08
      to 0.33). REVIEWER'S CONCLUSIONS: Anti-emetic medication appears to reduce the
      frequency of nausea in early pregnancy. There is some evidence of adverse
      effects, but there is very little information on effects on fetal outcomes from
      randomised controlled trials. Of newer treatments, pyridoxine (vitamin B6)
      appears to be more effective in reducing the severity of nausea. The results from
      trials of P6 acupressure are equivocal. No trials of treatments for hyperemesis
      gravidarum show any evidence of benefit. Evidence from observational studies
      suggests no evidence of teratogenicity from any of these treatments.

PMID- 14583915
TI  - Closure versus non-closure of the peritoneum at caesarean section.
AB  - BACKGROUND: Caesarean section is a very common surgical procedure world wide.
      Suturing the peritoneal layers at caesarean section may or may not confer
      benefit, hence the need to evaluate whether this step should be omitted or not.
      OBJECTIVES: The objective of this review was to assess the effects of non-closure
      as an alternative to closure of the peritoneum at caesarean section on intra
      operative, immediate and long-term postoperative and long-term outcomes. SEARCH
      STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register
      (November 2002). SELECTION CRITERIA: Controlled trials comparing leaving the
      visceral and/or parietal peritoneum unsutured at caesarean section with a
      technique which involves suturing the peritoneum in women undergoing elective or
      emergency caesarean section. DATA COLLECTION AND ANALYSIS: Trial quality was
      assessed and data were extracted by two reviewers. MAIN RESULTS: Nine trials
      involving 1811 women were included and analysed. The methodological quality of
      the trials was variable. Non-closure of the peritoneum reduced operating time
      whether both or either layer was not sutured. For both layers, the operating time
      was reduced by 7.33 minutes, 95% confidence interval (CI) -8.43 to -6.24. There
      was significantly less postoperative fever and reduced postoperative stay in
      hospital for visceral peritoneum and for both layer non-closure. There were no
      other statistically significant differences. The trend for analgesia requirement
      and wound infection tended to favour non-closure, while endometritis results were
      variable. Long-term follow up in one trial showed no significant differences. The
      power of the study to show differences was low. REVIEWER'S CONCLUSIONS: There was
      improved short-term postoperative outcome if the peritoneum was not closed. Long
      term studies following caesarean section are limited, but data from other
      surgical procedures are reassuring. There is at present no evidence to justify
      the time taken and cost of peritoneal closure.

PMID- 14583916
TI  - Spironolactone versus placebo or in combination with steroids for hirsutism
      and/or acne.
AB  - BACKGROUND: Hirsutism is the presence of excessive hair growth in women and is an
      important cosmetic condition often resulting in severe distress. Hirsutism is
      most often caused by increased production of male sex hormones also known as
      androgens. It is also affected by increased sensitivity to androgens in the hair
      follicles, and the secretory glands around the hair follicles, called sebaceous
      glands. Spironolactone is an antiandrogen and aldosterone antagonist used to
      treat hirsutism. OBJECTIVES: The objective of this review was to investigate the
      effectiveness of spironolactone and/or in combination with steroids (oral
      contraceptive pill included) in reducing excess hair growth and/or acne in women.
      SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility
      Group trials register (searched 12 June 2003). The Cochrane Menstrual Disorders
      and Subfertility Group register is based on regular searches of MEDLINE, EMBASE,
      CINAHL, PsycINFO and CENTRAL, the handsearching of 20 relevant journals and
      conference proceedings, and searches of several key grey literature sources. In
      addition, all reference lists of relevant trials were searched and drug companies
      contacted for details of unpublished trials. SELECTION CRITERIA: All randomised
      controlled comparisons of spironolactone versus: placebo, steroids (oral
      contraceptive pill included), spironolactone of varying dosages, or
      spironolactone and steroids versus steroids alone when used to reduce hair growth
      and acne in women. DATA COLLECTION AND ANALYSIS: Seven trials were included in
      the review, eight trials were excluded. Two other trials are awaiting assessment.
      All included trials were small (no more than 41 participants) randomised and
      controlled. Only one trial studied acne as an outcome, the remainder were
      concerned with hirsutism. Two trials investigated spironolactone versus placebo;
      one trial was a dosage studies of spironolactone; one trial compared
      spironolactone with spironolactone in combination with dexamethasone; one trial
      used topical spironolactone for the treatment of acne, one trial compared three
      treatments; spironolactone, finasteride, cyproterone acetate. Major outcome
      measures include the following: subjective observations, Ferriman and Gallwey
      hair scores, hormonal and biochemical parameters, side effects, sebum production
      measurement. MAIN RESULTS: All sample populations were small and confidence
      intervals were wide. In the two trials that compared 100 mg of spironolactone
      with placebo significant differences were reported for subjective improvements in
      hair growth (OR 7.18, 95% CI 1.96 to 26.28), Ferriman-Galwey score (WMD 7.20, 95%
      CI -10.98 to -3.42)). The remaining comparisons were not statistically
      significant. There were statistically significant improvements in Ferriman-Galwey
      scores 12 months after the end of treatment in those women who received 100mg/day
      spironolactone compared to 12.5 mg/day cyproterone acetate (first 10 days of
      cycle) (WMD -1.18, 95% CI -2.1 to -0.26) and 5mg/day finasteride (WMD -2.34, 95%
      CI -3.23 to -1.45). REVIEWER'S CONCLUSIONS: Six months treatment with 100 mg/day
      spironolactone compared with placebo was associated with a statistically
      significant subjective improvement in hair growth and a decrease in Ferriman
      Galwey scores. Spironolactone 100mg/day is superior to finasteride 5 mg/day and
      low dose cyproterone acetate 12.5 mg/day (first 10 days of cycle) up to 12 months
      after the end of treatment. The effectiveness of treatment for acne vulgaris
      cannot be determined due to the small sample populations involved in the trials.
      Its value in clinical practice is difficult to assess from currently available
      research.

PMID- 14583917
TI  - Corticosteroids for maintenance of remission in Crohn's disease.
AB  - BACKGROUND: The efficacy of corticosteroids in the setting of maintenance therapy
      for Crohn's disease has never been clearly demonstrated. It would be important to
      determine, based upon the currently available data from controlled trials, if the
      use of chronic corticosteroid therapy is of benefit in patients with quiescent
      Crohn's disease or if there is an identifiable subgroup of Crohn's disease
      patients, such as those in whom therapy cannot be successfully tapered, who might
      benefit from such treatment. OBJECTIVES: To evaluate the effectiveness and safety
      of conventional systemic corticosteroid therapy in maintaining clinical remission
      in Crohn's disease. SEARCH STRATEGY: A computer-assisted search of the on-line
      bibliographic database MEDLINE of studies published in English, French, Spanish,
      Italian and German between 1966 and July, 2003. Manual searches of the reference
      lists from the potentially relevant studies were performed in order to identify
      additional studies that may have been missed using the computer-assisted search
      strategy. Proceedings from major gastrointestinal meetings were also manually
      searched from 1985 to 2003 in order to identify unpublished studies. The Cochrane
      Central Register of Controlled Trials and the Inflammatory Bowel Disease Review
      Group Specialized Trials Register were also searched. SELECTION CRITERIA:
      Randomized double-blind placebo-controlled trials involving patients of any age
      with Crohn's disease in clinical remission as defined by a CDAI < 150 or by the
      presence of no symptoms or only mild symptoms at the time of entry into the
      trial. The experimental treatment consisted of oral conventional corticosteroid
      therapy (excluding budesonide, fluticasone, etc). Clinical disease relapse was
      used as the outcome measure of interest. DATA COLLECTION AND ANALYSIS: Eligible
      studies were selected by 4 reviewers and data were extracted onto standardized
      data extraction forms. Disagreements in eligibility or data extraction were
      resolved by consensus. Data were converted into individual 2x2 tables for each
      study. The presence of significant heterogeneity among studies was tested using
      the chi-square test. The 2x2 tables were synthesized into a summary test
      statistic using the pooled odds ratio and 95% confidence intervals as described
      by Cochran and Mantel and Haenszel (the 'odds ratio' in MetaView). A fixed
      effects model was used for the pooling of data. MAIN RESULTS: Four studies were
      initially judged as being eligible for inclusion. After obtaining additional
      information on one of the studies it was excluded because it was not double
      blind. The total number of subjects included in the analysis at the time points
      of 6, 12 and 24 months were 142, 131 and 95 for the corticosteroid group and 161,
      138 and 87 for the control group. The odds ratios for relapse on active treatment
      and the corresponding 95% confidence intervals were 0.71 (0.39, 1.31), 0.82
      (0.47, 1.43) and 0.72 (0.38, 1.35) at 6, 12 and 24 months. REVIEWER'S
      CONCLUSIONS: The use of conventional systemic corticosteroids in patients with
      clinically quiescent Crohn's disease does not appear to reduce the risk of
      relapse over a 24 month period of follow-up. This review updates the existing
      review of corticosteroids for maintaining remission of Crohn's disease which was
      published in the Cochrane Library (Issue 2, 2003).

PMID- 14583918
TI  - Interventions for preventing falls in elderly people.
AB  - BACKGROUND: Approximately 30 per cent of people over 65 years of age and living
      in the community fall each year; the number is higher in institutions. Although
      less than one fall in 10 results in a fracture, a fifth of fall incidents require
      medical attention. OBJECTIVES: To assess the effects of interventions designed to
      reduce the incidence of falls in elderly people (living in the community, or in
      institutional or hospital care). SEARCH STRATEGY: We searched the Cochrane
      Musculoskeletal Group specialised register (January 2003), Cochrane Central
      Register of Controlled Trials (The Cochrane Library, Issue 1, 2003), MEDLINE
      (1966 to February 2003), EMBASE (1988 to 2003 Week 19), CINAHL (1982 to April
      2003), The National Research Register, Issue 2, 2003, Current Controlled Trials
      (www.controlled-trials.com accessed 11 July 2003) and reference lists of
      articles. No language restrictions were applied. Further trials were identified
      by contact with researchers in the field. SELECTION CRITERIA: Randomised trials
      of interventions designed to minimise the effect of, or exposure to, risk factors
      for falling in elderly people. Main outcomes of interest were the number of
      fallers, or falls. Trials reporting only intermediate outcomes were excluded.
      DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality
      and extracted data. Data were pooled using the fixed effect model where
      appropriate. MAIN RESULTS: Sixty two trials involving 21,668 people were
      included. Interventions likely to be beneficial: Multidisciplinary,
      multifactorial, health/environmental risk factor screening/intervention
      programmes in the community both for an unselected population of older people (4
      trials, 1651 participants, pooled RR 0.73, 95%CI 0.63 to 0.85), and for older
      people with a history of falling or selected because of known risk factors (5
      trials, 1176 participants, pooled RR 0.86, 95%CI 0.76 to 0.98), and in
      residential care facilities (1 trial, 439 participants, cluster-adjusted
      incidence rate ratio 0.60, 95%CI 0.50 to 0.73) A programme of muscle
      strengthening and balance retraining, individually prescribed at home by a
      trained health professional (3 trials, 566 participants, pooled relative risk
      (RR) 0.80, 95% confidence interval (95%CI) 0.66 to 0.98) Home hazard assessment
      and modification that is professionally prescribed for older people with a
      history of falling (3 trials, 374 participants, RR 0.66, 95% CI 0.54 to 0.81)
      Withdrawal of psychotropic medication (1 trial, 93 participants, relative hazard
      0.34, 95%CI 0.16 to 0.74) Cardiac pacing for fallers with cardioinhibitory
      carotid sinus hypersensitivity (1 trial, 175 participants, WMD -5.20, 95%CI -9.40
      to -1.00) A 15 week Tai Chi group exercise intervention (1 trial, 200
      participants, risk ratio 0.51, 95%CI 0.36 to 0.73). Interventions of unknown
      effectiveness: Group-delivered exercise interventions (9 trials, 1387
      participants) Individual lower limb strength training (1 trial, 222 participants)
      Nutritional supplementation (1 trial, 46 participants) Vitamin D supplementation,
      with or without calcium (3 trials, 461 participants) Home hazard modification in
      association with advice on optimising medication (1 trial, 658 participants), or
      in association with an education package on exercise and reducing fall risk (1
      trial, 3182 participants) Pharmacological therapy (raubasine-dihydroergocristine,
      1 trial, 95 participants) Interventions using a cognitive/behavioural approach
      alone (2 trials, 145 participants) Home hazard modification for older people
      without a history of falling (1 trial, 530 participants) Hormone replacement
      therapy (1 trial, 116 participants) Correction of visual deficiency (1 trial, 276
      participants). Interventions unlikely to be beneficial: Brisk walking in women
      with an upper limb fracture in the previous two years (1 trial, 165
      participants). REVIEWER'S CONCLUSIONS: Interventions to prevent falls that are
      likely to be effective are now available; less is known about their effectiveness
      in preventing fall-related injuries. Costs per fall prevented have been
      established for four of the interventions and careful economic modelling in the
      context of the local healthcare system is important. Some potential interventions
      are of unknown effectiveness and further research is indicated.

PMID- 14583919
TI  - Inositol for respiratory distress syndrome in preterm infants.
AB  - BACKGROUND: Inositol is an essential nutrient required by human cells in culture
      for growth and survival. Inositol promotes maturation of several components of
      surfactant and may play a critical role in fetal and early neonatal life.
      OBJECTIVES: To assess the effectiveness/safety of supplementary inositol in
      preterm infants with RDS in reducing adverse neonatal outcomes. SEARCH STRATEGY:
      MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were
      searched in July, 2003 using key words: inositol and infant-newborn and random
      allocation or controlled trial or randomized trial (RCT). The reference lists of
      identified RCTs, personal files and Science Citation Index were searched.
      Unpublished additional information was obtained from the authors of one RCT
      published in abstract form. SELECTION CRITERIA: All randomized controlled trials
      of inositol supplementation to preterm infants with a control group that received
      a placebo or no intervention were included. Outcomes of interest were
      bronchopulmonary dysplasia (BPD), death, BPD or death, retinopathy of prematurity
      (ROP), intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), and
      sepsis. DATA COLLECTION AND ANALYSIS: Data on neonatal outcomes were abstracted
      independently by the two researchers and any discrepancy was resolved through
      consensus. Revman was used for analysis of the data. MAIN RESULTS: Five reports
      of three RCTs were identified. One report was a duplicate publication. One new
      report included both randomized and non-randomized patients and data could not be
      extracted for the randomized neonates only and the study was excluded. An interim
      report of this study previously published as an abstract was included in the
      previous version of this review. The outcome of death or bronchopulmonary
      dysplasia was reported in two trials, and was found to be significantly reduced
      (RR 0.56, 95% CI 0.42, 0.77; RD -0.215, 95% CI -0.323, -0.107). The outcome of
      death was reported in two trials and was found to be significantly reduced (RR
      0.48, 95% CI 0.28, 0.80; RD -0.131, 95% CI -0.218, -0.043). Retinopathy of
      prematurity, stage 4 or needing therapy, was reported in two trials, and was
      found to be significantly reduced (RR 0.09, 95% CI 0.01, 0.67; RD -0.078, 95% CI 
      0.128, -0.027). Intraventricular hemorrhage, grade III-IV, was significantly
      decreased (RR 0.55, 95% CI 0.32, 0.95; RD -0.090, 95% CI -0.170, -0.010). Neither
      sepsis nor necrotizing enterocolitis outcomes were increased. When a secondary
      analysis was done excluding a study published in abstract form, the results
      differed only in that there was a significant reduction in retinopathy of
      prematurity, any stage (RR 0.53, 95% CI 0.29, 0.97; RD -0.082, 95% CI -0.159,
      0.005). REVIEWER'S CONCLUSIONS: Inositol supplementation results in statistically
      significant and clinically important reductions in important short-term adverse
      neonatal outcomes. A multi-center RCT of appropriate size is justified to confirm
      these findings.

PMID- 14583920
TI  - Vaccines for preventing pneumococcal infection in adults.
AB  - BACKGROUND: Diseases caused by Streptococcus pneumoniae (S. pneumoniae) continue
      to cause substantial morbidity and mortality throughout the world. Polysaccharide
      pneumococcal vaccines have been developed for over 50 years and may have the
      potential to prevent disease and death. OBJECTIVES: To assess the effectiveness
      of polysaccharide pneumococcal vaccination in preventing disease or death in
      adults. SEARCH STRATEGY: Trials were identified by electronic searches of the
      Cochrane Central Register of Controlled Trials (CENTRAL) issue 2, 2003 (which
      includes the Cochrane ARI Group's specialised register); MEDLINE (January 1966 to
      June 2003); and EMBASE (1974 to June 2003). We searched existing literature. The
      bibliographies of all newly revealed studies were read in order to identify
      further studies. The vaccine manufacturers, the lead authors of newly identified
      studies not included in existing meta-analyses were contacted. SELECTION
      CRITERIA: A) Prospective, randomised or quasi-randomised studies comparing
      pneumococcal vaccines with placebo, control vaccines or no intervention.B) Case
      control studies (including indirect cohort studies) assessing pneumococcal
      vaccine effectiveness against invasive pneumococcal disease. Cohort studies are
      excluded. DATA COLLECTION AND ANALYSIS: A) Randomised studies. Trial quality
      assessment was conducted by two reviewers (JH and DT). Data extraction was done
      by three reviewers (JH, DT, KD). There were many instances of unclear or
      incomplete data in the trial reports, and the final dataset was arrived at after
      much deliberation and discussion, including comparison with the data used in two
      previous reviews of this question. Due to the age of the trials (dating back to
      1954 in one case) it was not generally possible to obtain clarification from the
      authors, though a partial clarification was achieved in one case.B) Non
      randomised studies. Study quality was assessed by two reviewers (RA and KD). MAIN
      RESULTS: The combined results from the randomised studies fail to show that the
      polysaccharide pneumococcal vaccine is effective in preventing either pneumonia
      (outcome 6: odds ratio = 0.77, confidence interval 0.58, 1.02, number = 14) or
      death (outcome 8: odds ratio 0.90, confidence interval 0.76, 1.07, number = 11).
      Despite encouraging data from some very early trials, pooling trials published
      from 1977 on suggests there is no effect (outcome 6; odds ratio = 0.96,
      confidence interval 0.80, 1.15, number = 12; outcome 9: odds ratio = 0.98,
      confidence interval 0.88, 1.09, number = 10). The available data cannot
      distinguish whether this heterogeneity in results is due to improvements in trial
      methodology and reporting, to differences in trial setting or to real loss of
      efficacy over time. This is because the early, poorly reported trials were
      conducted in high-risk healthy populations where the expected benefit is
      greatest. The case-control studies show significant efficacy in preventing
      invasive pneumococcal disease: OR 0.47 (CI 0.37, 0.59) corresponding to an
      efficacy of 53%. REVIEWER'S CONCLUSIONS: While polysaccharide pneumococcal
      vaccines do not appear to reduce the incidence of pneumonia or death in adults
      with or without chronic illness, or in the elderly (55 years and above), the
      evidence from non-randomised studies suggests that the vaccines are effective in
      the reducing the incidence of the more specific outcome, invasive pneumococcal
      disease, among adults and the immunocompetent elderly (55 years and above).
      Surveillance data suggest that infection rates vary widely between and also
      within countries, but a typical figure in developed countries is 0.01%, or 10 per
      100,000 per year. Efficacy of 50% then corresponds to a number-needed-to-treat
      (NNT) of 20,000 vaccinations per infection avoided, and perhaps 50,000 per death
      avoided.

PMID- 14583921
TI  - Interventions for treating proximal humeral fractures in adults.
AB  - BACKGROUND: Proximal humeral fractures are common yet the management of these
      injuries varies widely. In particular, the role and timing of any surgical
      intervention have not been clearly defined. OBJECTIVES: To collate and evaluate
      the scientific evidence supporting the various methods used for treating proximal
      humeral fractures. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal
      Injuries Group specialised register, the Cochrane Central Register of Controlled
      Trials, PEDro, MEDLINE (1966 to May week 4 2003), EMBASE (1980 to 2003 week 22),
      CINAHL (1982 to May week 3 2003), AMED (1985 to May 2003), the National Research
      Register (UK), Current Controlled Trials, and bibliographies of trial reports.
      The search was completed in May 2003. SELECTION CRITERIA: All randomised studies
      pertinent to the treatment of proximal humeral fractures were selected. DATA
      COLLECTION AND ANALYSIS: Independent quality assessment and data extraction were
      performed by two reviewers. Although quantitative data from trials are presented,
      trial heterogeneity prevented pooling of results. MAIN RESULTS: Twelve randomised
      trials were included. All were small; the largest study involved only 86
      patients. Bias in these trials could not be ruled out. Eight trials evaluated
      conservative treatment, three compared surgery with conservative treatment and
      one compared two surgical techniques. In the 'conservative' group there was very
      limited evidence indicating that the type of bandage used made any difference in
      terms of time to fracture union and the functional end result. However, an arm
      sling was generally more comfortable than a body bandage. There was some evidence
      that 'immediate' physiotherapy, without routine immobilisation, compared with
      that delayed until after three weeks immobilisation resulted in less pain and
      both faster and potentially better recovery in patients with undisplaced two-part
      fractures. Similarly, there was evidence that mobilisation at one week instead of
      three weeks alleviated pain in the short term without compromising long term
      outcome. Two trials provided some evidence that patients, when given sufficient
      instruction to pursue an adequate physiotherapy programme, could generally
      achieve a satisfactory outcome if allowed to exercise without supervision.
      Operative reduction improved fracture alignment in two trials. However, in one
      trial, surgery was associated with a greater risk of complication, and did not
      result in improved shoulder function. In one trial, hemi-arthroplasty resulted in
      better short-term function with less pain and less need for help with activities
      of daily living when compared with conservative treatment for severe injuries.
      Fracture fixation of severe injuries was associated with a high rate of re
      operation in one trial, comparing tension-band wiring fixation with hemi
      arthroplasty. There was very limited evidence that similar outcomes resulted from
      mobilisation at one week instead of three weeks after surgical fixation.
      REVIEWER'S CONCLUSIONS: Only tentative conclusions can be drawn from the
      available randomised trials, which do not provide sufficient evidence for many of
      the decisions that need to be made in contemporary fracture management. Early
      physiotherapy, without immobilisation, may be sufficient for some types of
      undisplaced fractures. It is unclear whether operative intervention, even for
      specific fracture types, will produce consistently better long term outcomes.
      There is a need for good quality evidence for the management of these fractures.

PMID- 14583922
TI  - Radiant warmers versus incubators for regulating body temperature in newborn
      infants.
AB  - BACKGROUND: The provision of a thermoneutral environment is an essential
      component of the immediate and longer term care of newborn infants. A variety of
      methods are currently employed including incubators and open-care systems, with
      or without modifications such as heat shields and plastic wrap. The system used
      must allow ready access to the infant but should also minimise alterations in the
      immediate environment. OBJECTIVES: To assess the effects of radiant warmers
      versus incubators on neonatal fluid and electrolyte balance, morbidity and
      mortality. SEARCH STRATEGY: The standard search strategy of the Cochrane Neonatal
      Review Group was used. This included searches of electronic databases: Oxford
      Database of Perinatal Trials, Cochrane Central Register of Controlled Trials
      (CENTRAL, The Cochrane Library, Issue 1, 2003), MEDLINE (1966 -2003), and CINAHL
      (1982-2003), previous reviews including cross references, abstracts, conferences,
      symposia proceedings, expert informants and journal hand searching mainly in the
      English language. SELECTION CRITERIA: Randomised or quasi-randomised trials in
      which radiant warmers were compared to incubators in a neonatal population. DATA
      COLLECTION AND ANALYSIS: Independent data extraction and quality assessment of
      included trials was conducted by the authors. Data were analysed using relative
      risk (RR) and weighted mean difference (WMD). Results are presented with 95%
      confidence intervals. Meta-analysis was undertaken using a fixed effect model.
      MAIN RESULTS: Eight studies are included in this review; six employed a crossover
      design. In the overall comparison of radiant warmers vs incubators, radiant
      warmers caused a statistically significant increase in insensible water loss
      (IWL) [WMD 0.94g/Kg/day (95% CI 0.47, 1.41)] and a trend towards increased oxygen
      consumption which was not statistically significant [WMD 0.27mL/kg/min (95% CI 
      0.09, 0.63)]. Due to small numbers, effects on important clinical outcomes could
      not be adequately assessed. A comparison of radiant warmers with heat shields vs
      incubators without heat shields showed a trend for increased IWL in the radiant
      warmer group, which was not statistically significant. No difference was shown in
      oxygen consumption. REVIEWER'S CONCLUSIONS: Radiant warmers result in increased
      IWL compared to incubators. This needs to be taken into account when calculating
      daily fluid requirements. The results of this review do not provide sufficient
      evidence concerning effects on important outcomes to guide clinical practice.
      Further randomised controlled trials are required to assess the effects of
      radiant warmers versus incubators in neonatal care on important short and long
      term outcomes, with particular attention to extremely low birthweight infants in
      the early neonatal period.

PMID- 14583923
TI  - Balneotherapy for rheumatoid arthritis.
AB  - BACKGROUND: Balneotherapy (spa therapy) for patients with arthritis is one of the
      oldest forms of therapy. One of the aims of balneotherapy is to soothe the pain,
      improve joint motion and as a consequence to relieve people' suffering and make
      them feel well. OBJECTIVES: To perform a systematic review on the effectiveness
      of balneotherapy for rheumatoid arthritis. SEARCH STRATEGY: Using the Cochrane
      search strategy, studies were found by screening: 1) The MEDLINE CD-ROM database
      from 1966 to June 2002 and 2) the database from the Cochrane 'Rehabilitation and
      Related Therapies' Field, the Pedro database up to June 2002. Also, 3) reference
      checking and 4) personal communications with authors was carried out to retrieve
      eligible studies. Date of the most recent literature search: June, 2002 SELECTION
      CRITERIA: Studies were eligible if they were randomised controlled trials (RCTs)
      comparing balneotherapy with any other intervention or with no intervention.
      Included participants all suffered from definite or classical rheumatoid
      arthritis (RA) as defined by the American Rheumatism Association Criteria (ARA)
      or by the criteria of Steinbrocker. At least one of the WHO/ILAR core set of
      endpoints for RA clinical trials had to be among the main outcome measures. DATA
      COLLECTION AND ANALYSIS: The Delphi list was the criteria list used to assess the
      components of methodological quality. Two reviewers carried out quality
      assessment and data extraction of the studies. Disagreements were solved by
      consensus. MAIN RESULTS: Six trials, representing 355 people, were included in
      this review. Most trials reported positive findings (the absolute improvement in
      measured outcomes ranged from 0 to 44%), but were methodologically flawed to some
      extent. A 'quality of life' outcome was reported by two trials. None of the
      trials performed an intention-to-treat analysis and only two performed a
      comparison of effects between groups. Pooling of the data was not performed;
      because of heterogeneity of the studies, multiple outcome measurements, and the
      overall data presentation was too scarce. REVIEWER'S CONCLUSIONS: One cannot
      ignore the positive findings reported in most trials. However the scientific
      evidence is insufficient because of the poor methodological quality, the absence
      of an adequate statistical analysis, and the absence, for the patient, of most
      essential outcome measures (pain, self assessed function, quality of life).
      Therefore, the noted "positive findings" should be viewed with caution. Because
      of the methodological flaws an answer about the apparent effectiveness of
      balneotherapy cannot be provided at this moment. A large, methodological sound
      trial is needed.

PMID- 14583924
TI  - Antithrombotic agents for preventing thrombosis after infrainguinal arterial
      bypass surgery.
AB  - BACKGROUND: Chronic peripheral arterial disease (PAD) is frequently treated by
      implantation of either an infrainguinal autologous venous or artificial graft.
      One-year occlusion rates for infrainguinal bypasses vary between 15 and 75%,
      depending on the site of distal anastomosis, length, quality, and material of the
      graft, but also on other factors such as proximal inflow and distal outflow
      conditions. To prevent graft occlusion, patients are usually treated with either
      an antiplatelet or antithrombotic drug, or a combination of both. Little is known
      about which drug is optimal to prevent infrainguinal graft occlusion. OBJECTIVES:
      To evaluate whether antithrombotic treatment in patients with chronic PAD
      undergoing infrainguinal bypass surgery improves graft patency, limb salvage and
      survival by performing a meta-analysis of performed RCTs. SEARCH STRATEGY: The
      search strategy was that adopted by the Cochrane Review Group on Peripheral
      Vascular Diseases. Additional data bases were reviewed (Reference lists of papers
      resulting from this search, MEDLINE from 1966-onwards and EMBASE from 1980
      onwards using the terms 'anticoagulant' and 'arterial surgery'. SELECTION
      CRITERIA: The methodological quality of each trial was assessed independently by
      at least two reviewers using the checklist provided by the Peripheral Vascular
      Diseases Collaborative Review Group, with emphasis on concealment of
      randomisation. Each trial was given an allocation score of A (clearly concealed),
      B (unclear if concealed), or C (clearly not concealed) and a summary score of A
      (low risk of bias), B (moderate risk), or C (high risk). Trials scoring A were
      included and those scoring C were excluded. For a trial scoring B, an attempt was
      made to obtain more information by contacting the author. DATA COLLECTION AND
      ANALYSIS: For each trial, the number of patients originally allocated to each
      treatment group was extracted from the data and an 'intention to treat' analysis
      performed. Data collection on each trial included inclusion and exclusion
      criteria, patient details, type of graft, type and dose of antithrombotic therapy
      used, outcome, and side effects. The treatment and control groups were compared
      for important prognostic factors and differences described. If any of the above
      data was not available, further information was sought from the author. However,
      the heterogeneity between trials could not be tested due to inaccessible data.
      Data were synthesized by comparing group results. MAIN RESULTS: The analysis
      including four trials which evaluated vitamin K antagonists (VKA) versus no VKA
      indicate, that oral anticoagulation tendentially favours venous but not
      artificial graft patency as well as limb salvage and survival. Two other studies
      comparing VKA with aspirin or aspirin/dipyridamole supported evidence for a
      positive effect of VKA on the patency of venous but not artificial grafts.
      Subgroup analysis for artificial grafts as performed in one trial showed a
      favourable effect of antiplatelet agents on synthetic bypasses. In two trials
      with a relatively small number of patients low molecular weight heparin treatment
      was associated with a lower incidence of early postoperative graft thrombosis
      compared to treatment with unfractionated heparin. In one trial infusion of
      antithrombin concentrate was reported to have a negative effect on intraoperative
      graft thrombosis necessitating the study to be stopped before termination.
      Perioperative administration of ancrod was compared to unfractionated heparin
      showing no benefit of one drug compared to the other. REVIEWER'S CONCLUSIONS:
      Patients operated for an infrainguinal venous graft might benefit from treatment
      with VKA, whereas patients receiving an artificial graft might profit more from
      platelet inhibitors (aspirin). However, the evidence is not conclusive.
      Randomised controlled trials with larger patient numbers comparing antithrombotic
      therapies with either placebo or antiplatelet therapies are called for in the
      future.

PMID- 14583925
TI  - Calcium channel blockers for acute traumatic brain injury.
AB  - BACKGROUND: Acute traumatic brain injury is a major cause of death and
      disability. Calcium channel blockers (calcium antagonists) have been used in an
      attempt to prevent cerebral vasospasm after injury, maintain blood flow to the
      brain, and so prevent further damage. OBJECTIVES: To estimate the effects of
      calcium channel blockers in patients with acute traumatic brain injury, and in a
      subgroup of brain injury patients with traumatic subarachnoid haemorrhage. SEARCH
      STRATEGY: Handsearching and electronic searching for randomised controlled
      trials. SELECTION CRITERIA: Randomised controlled trials in patients with all
      levels of severity of clinically diagnosed acute traumatic brain injury. DATA
      COLLECTION AND ANALYSIS: Two reviewers independently assessed the identified
      studies for eligibility and extracted data from each study. Summary odds ratios
      were calculated using the Mantel-Haenszel method. MAIN RESULTS: Six RCTs were
      identified as eligible for inclusion in the systematic review. The effect of
      calcium channel blockers on the risk of death was reported in five of the RCTs.
      The pooled odds ratio (OR) for the five studies was 0.91 (95% confidence interval
      [95%CI] 0.70-1.17). For the four RCTs that reported death and severe disability
      (unfavourable outcome), the pooled odds ratio was 0.85 (95%CI 0.68-1.07). In the
      two RCTs which reported the risk of death in a subgroup of traumatic subarachnoid
      haemorrhage patients, the pooled odds ratio was 0.59 (95%CI 0.37-0.94). Three
      RCTs reported death and severe disability as an outcome in this subgroup, and the
      pooled odds ratio was 0.67 (95%CI 0.46-0.98). REVIEWER'S CONCLUSIONS: This
      systematic review of randomised controlled trials of calcium channel blockers in
      acute traumatic head injury patients shows that considerable uncertainty remains
      over their effects. The effect of nimodipine in a subgroup of brain injury
      patients with subarachnoid haemorrhage shows a beneficial effect, though the
      increase in adverse reactions suffered by the intervention group may mean that
      the drug is harmful for some patients.

PMID- 14583926
TI  - Continuous versus intermittent beta-agonists in the treatment of acute asthma.
AB  - BACKGROUND: Patients with acute asthma treated in the emergency department are
      frequently treated with intermittent inhaled beta-agonists delivered by
      nebulisation. The use of continuous beta-agonist (CBA) via nebulisation in the
      emergency setting may offer additional benefits in acute asthma. OBJECTIVES: To
      determine the efficacy (e.g., reductions in admission, improvement in pulmonary
      functions) and risks (e.g., adverse events, effects on vital signs) of continuous
      versus intermittent inhaled beta-agonists for the treatment of patients with
      acute asthma managed in the emergency department. SEARCH STRATEGY: Randomised
      controlled trials were identified from the Cochrane Airways Review Group "Asthma
      and WHEEZ*" Register which is a compilation of systematic searches of CINAHL,
      EMBASE, MEDLINE and CENTRAL and hand searching of 20 respiratory journals. In
      addition, primary authors and content experts were contacted to identify eligible
      studies. Bibliographies from included studies, known reviews and texts were also
      searched. The search is considered updated to June 2003. SELECTION CRITERIA: Only
      randomised controlled trials (RCTs) were eligible for inclusion. Studies were
      included if patients presented with acute asthma and were treated with either
      continuous or intermittent inhaled beta-agonists early in the ED treatment.
      "Continuous" nebulisation was defined as truly continuous aerosol delivery of
      beta-agonist medication (e.g., using a commercially available large-volume
      nebuliser, or a small-volume nebuliser with infusion pump) or sufficiently
      frequent nebulisations that medication delivery was effectively continuous (i.e.,
      1 nebulisation every 15 minutes or > 4 nebulisations per hour). Studies also
      needed to report either pulmonary function or admission results. Two reviewers
      independently selected potentially relevant articles and two additional reviewers
      independently selected articles for inclusion. Methodological quality was
      independently assessed by two reviewers. DATA COLLECTION AND ANALYSIS: Data were
      extracted independently by two reviewers if the authors were unable to verify the
      validity of information. Missing data were obtained from authors or calculated
      from other data presented in the paper. The data were analysed using the Cochrane
      Review Manager (Version 4.1). Relative risks (RR), weighted mean differences
      (WMD) and standardized mean differences (SMD) are reported with corresponding 95%
      confidence intervals (CI); both peak expiratory flow rates (PEFR) and forced
      expiratory volume in one second (FEV-1) data are reported. MAIN RESULTS: 165
      trials were reviewed and eight were included; a total of 461 patients have been
      studied (229 with CBA; 232 with intermittent beta-agonists). Overall, admission
      to hospital was reduced with CBA compared to intermittent beta-agonists (RR:
      0.68; 95% CI: 0.5 to 0.9); patients with severe airway obstruction at
      presentation appeared to benefit most from this intervention (RR: 0.64; 95% CI:
      0.5 to 0.9). Patients receiving CBA demonstrated small but statistically
      significant improvements in pulmonary function tests when all studies were
      pooled. Patients receiving CBA had greater improvements in % predicted FEV-1
      (SMD: 0.3; 95% CI: 0.03 to 0.5) and PEFR (SMD: 0.33; 95% CI: 0.1 to 0.5); this
      effect was observed by 2-3 hours. Continuous treatment was generally well
      tolerated, with no clinically important differences observed in pulse rate (WMD: 
      2.87; 95% CI: -6.0 to 0.3) or blood pressure (WMD: -1.75; 95% CI: -5.6 to 2.1)
      between the treatment groups. Tremor was equally common in both groups (OR: 0.81;
      95% CI: 0.5 to 1.3) and potassium concentration was unchanged (WMD: 0.02; 95% CI:
      -0.2 to 0.2). REVIEWER'S CONCLUSIONS: Current evidence supports the use of CBA in
      patients with severe acute asthma who present to the emergency department to
      increase their pulmonary functions and reduce hospitalisation. Moreover, CBA
      treatment appears to be safe and well tolerated in patients who receive it.

PMID- 14583927
TI  - Cyproterone acetate for hirsutism.
AB  - BACKGROUND: Hirsutism is a distressing and relatively common endocrine problem in
      women which may prove difficult to manage. Cyproterone acetate, an anti-androgen,
      is frequently used to treat hirsutism, usually in combination with ethinyl
      estradiol. OBJECTIVES: The objective of this review was to investigate the
      effectiveness of cyproterone acetate alone, or in combination with ethinyl
      estradiol, in reducing hair growth in women with hirsutism secondary to ovarian
      hyperandrogenism. SEARCH STRATEGY: The Cochrane Menstrual Disorders and
      Subfertility Group trials register was searched (last search - 4 June 2002). The
      Cochrane Menstrual Disorders and Subfertility Group register is based on regular
      searches of MEDLINE (1966 to 2002), EMBASE (1980 to 2002), CINAHL (1982 to 2002),
      PsycINFO (1987 to 2002) and CENTRAL (Issue 2, 2002 of the Cochrane Library) the
      handsearching of several journals and conference proceedings, and searches of
      several key grey literature sources. All publications of randomised controlled
      trials of cyproterone acetate with or without estrogen versus placebo or other
      drug therapies for hirsutism were identified. SELECTION CRITERIA: All randomised
      controlled studies comparing:- cyproterone acetate to placebo- cyproterone
      acetate with ethinyl estradiol to placebo- cyproterone acetate with ethinyl
      estradiol to cyproterone acetate alone- cyproterone acetate (with or without
      estradiol) to other medical therapies for treatment of hirsutism. DATA COLLECTION
      AND ANALYSIS: Eleven studies were identified which fulfilled the inclusion
      criteria. Nine randomised studies were included in the review, and two were
      excluded because of insufficient information. Only one study had more than 100
      women included in the analysis. The major outcomes included: subjective
      improvement in hirsutism, changes in Ferriman Gallwey scores, changes in linear
      hair growth and hair shaft diameter, alterations in endocrine parameters, side
      effects to treatment, withdrawals during therapy MAIN RESULTS: There were no
      clinical trials comparing cyproterone acetate alone with placebo. There was one
      small study comparing cyproterone acetate in combination with ethinyl estradiol
      to placebo. In this study there was a significant subjective reduction in hair
      growth with cyproterone acetate therapy, although the confidence limits were
      large. There were no studies comparing cyproterone acetate alone with cyproterone
      acetate in combination with ethinyl estradiol to treat hirsutism. In studies
      where cyproterone acetate was compared to other drug modalities (ketoconazole,
      spironolactone, flutamide, finasteride, GnRH analogues) no difference in clinical
      outcome was noted. There were, however, endocrinological differences in androgen
      and estrogen levels between different drug therapies. There were insufficient
      data to assess differences in side effects between women treated with cyproterone
      acetate and other medical therapy. REVIEWER'S CONCLUSIONS: Cyproterone acetate
      combined with estradiol results in a subjective improvement in hirsutism compared
      to placebo. Clinical differences in outcome between cyproterone acetate and other
      medical therapies were not demonstrated in the studies included in this review.
      This may be because of the small size of the studies, lack of standardized
      assessment and lack of objective determinants of improvement in hirsutism. The
      endocrinological effects of the different drug therapies reflect the mode of
      action. Larger carefully designed studies are needed to compare efficacy and
      safety profiles between drug therapies for hirsutism.

PMID- 14583928
TI  - Allergen immunotherapy for asthma.
AB  - BACKGROUND: Allergen specific immunotherapy has long been a controversial
      treatment for asthma. Although beneficial effects upon clinically relevant
      outcomes have been demonstrated in randomised controlled trials, there remains a
      risk of severe and sometimes fatal anaphylaxis. The recommendations of
      professional bodies have ranged from cautious acceptance to outright dismissal.
      With increasing interest in new allergen preparations and new methods of
      delivery, it was time to conduct another systematic review of allergen specific
      immunotherapy for asthma. OBJECTIVES: The objective of this review was to assess
      the effects of allergen specific immunotherapy for asthma. SEARCH STRATEGY: We
      searched the Cochrane Airways Group trials register up to June 2001, MEDLINE,
      Dissertation Abstracts, Current Contents and reference lists of articles.
      SELECTION CRITERIA: Randomised controlled trials using various forms of allergen
      specific immunotherapy to treat asthma and reporting at least one clinical
      outcome. DATA COLLECTION AND ANALYSIS: Three reviewers independently assessed
      eligibility of studies for inclusion. Two reviewers independently performed
      quality assessment of studies. MAIN RESULTS: Seventy-five trials were included
      (52 of 54 previously included trials and 23 new trials). A total of 3,506
      participants (3,188 with asthma) were involved. There were 36 trials of
      immunotherapy for house mite allergy; 20 pollen allergy trials; ten animal dander
      allergy trials; two Cladosporium mould allergy, one latex and six trials looking
      at multiple allergens. Concealment of allocation was assessed as clearly adequate
      in only 15 of these trials. Significant heterogeneity was present in a number of
      comparisons. Overall, there was a significant reduction in asthma symptoms and
      medication and improvement in bronchial hyper-reactivity following immunotherapy.
      There was a significant improvement in asthma symptom scores (standardised mean
      difference -0.72, 95% confidence interval -0.99 to -0.33) and it would have been
      necessary to treat 4 (95%CI 3 to 5) patients with immunotherapy to avoid one
      deterioration in asthma symptoms. Overall it would have been necessary to treat 5
      (95%CI 4 to 6) patients with immunotherapy to avoid one requiring increased
      medication. Allergen immunotherapy significantly reduced allergen specific
      bronchial hyper-reactivity, with some reduction in non-specific bronchial hyper
      reactivity as well. There was no consistent effect on lung function. REVIEWER'S
      CONCLUSIONS: Immunotherapy reduces asthma symptoms and use of asthma medications
      and improves bronchial hyper-reactivity. One trial found that the size of the
      benefit is possibly comparable to inhaled steroids. The possibility of adverse
      effects (such as anaphylaxis) must be considered.

PMID- 14583929
TI  - Heparins and mechanical methods for thromboprophylaxis in colorectal surgery.
AB  - BACKGROUND: Colorectal surgery implies higher risk of postoperative
      thromboembolic complications as deep venous thrombosis (DVT) and pulmonary
      embolism (PE) than general surgery. The best prophylaxis in general surgery is
      heparin and graded compression stockings. No systematic review on combination
      prophylaxis or on thrombosis prophylaxis in colorectal surgery has been
      published. OBJECTIVES: To compare the incidence of postoperative thromboembolism
      after colorectal surgery using prophylactic methods focussing on heparins and
      mechanical methods alone and in combinations. SEARCH STRATEGY: Electronic
      searches was performed in PUBMED, EMBASE, LILACS and the Cochrane Library.
      Abstract books from major congresses were handsearched as were reference lists
      from previously performed reviews. SELECTION CRITERIA: RCT or CCT comparing
      prophylactic interventions and/or placebo. Outcomes were ascending venography,
      125 I-fibrinogen uptake test, ultrasound methods, pulmonary scintigraphy.
      Studies, using thermographic methods, other isotopic methods, plethysmographic
      methods, and purely clinical methods as the only diagnostic measure were
      excluded. 558 studies were identified - 477 were excluded. Only 3 of the
      identified studies focused exclusively on colorectal surgery. Studies of general
      surgery contain considerable numbers of colorectal patients. The authors of 66
      studies in general and/or abdominal surgery were contacted for retrieving the
      results from the colorectal patients. Answers were received from very few. 19
      studies entered this review. DATA COLLECTION AND ANALYSIS: All studies and all
      data extraction were performed by at least two of the authors. Outcome was deep
      venous thrombosis and/or pulmonary embolism. Analysis of bleeding complications
      were unfeasible. 12 meaningful outcomes were analysed by means of the fixed
      effects model with Peto Odds Ratios. MAIN RESULTS: Heparins versus no treatment:
      Any kind of heparincompared to no treatment or placebo (comparison 07.03, 11
      studies). Heparin is better in preventing DVT and/or PE with a Peto Odds ratio at
      0.32 (95% Confidence Interval 0.20-0.53) Unfractionated heparin versus low
      molecular weight heparin (comparison 08.03, 4 studies). The two treatments were
      found equally effective in preventing DVT and/or PE with a Peto Odds ratio 1.01
      (95% Confidence Interval 0.67-1.52). Mechanical methods (comparison 10.3, 2
      studies). The combination of graded compression stockings and LDH is better than
      LDH alone in preventing DVT and/or PE with a Peto Odds ratio at 4.17 (95%
      Confidence Interval 1.37-12.70). REVIEWER'S CONCLUSIONS: The optimal prophylaxis
      in colorectal surgery is the combination of graduated compression stockings and
      low-dose unfractionated heparin. The unfractionated heparin can be replaced with
      low molecular weight heparin.

PMID- 14583930
TI  - Gonadotrophin-releasing hormone analogues for endometriosis: bone mineral
      density.
AB  - BACKGROUND: Gonadotrophin-releasing hormone analogues (GnRHas) are generally well
      tolerated, and are effective in relieving the symptoms of endometriosis (Prentice
      2003). Unfortunately the low oestrogen state that they induce is associated with
      adverse effects including an acceleration in bone mineral density (BMD) loss.
      OBJECTIVES: To determine the effect of treatment with gonadotrophin-releasing
      hormone analogues (GnRHas) on the bone mineral density of women with
      endometriosis, compared to placebo, no treatment, or other treatments for
      endometriosis, including GnRHas with add-back therapy. SEARCH STRATEGY: We
      searched the Cochrane Menstrual Disorders and Subfertility Group's specialised
      register of controlled trials (23rd October 2002) and the Cochrane Central
      Register of Controlled Trials (Cochrane Library, issue 4, 2002). We also carried
      out electronic searches of MEDLINE (1966 - March Week 2 2003) and EMBASE (1980 -
      March Week 2 2003). We also searched the reference lists of articles and
      contacted researchers in the field. SELECTION CRITERIA: Prospective, randomised
      controlled studies of the use of GnRHas for the treatment of women with
      endometriosis were considered, where bone density measurements were an end point.
      The control arm of the studies was either placebo, no treatment, another medical
      therapy for endometriosis, or GnRHas with add-back therapy. DATA COLLECTION AND
      ANALYSIS: Two reviewers (JF and MS) independently assessed trial quality and
      extracted data. Study authors were contacted for additional information. MAIN
      RESULTS: Thirty studies involving 2,391 women were included, however only 15,
      involving 910 women, could be included in the meta-analysis. The meta-analysis
      showed that danazol and progesterone + oestrogen add-back are protective of BMD
      at the lumbar spine both during treatment and for up to six and twelve months
      after treatment, respectively. Between the groups receiving GnRHa and the groups
      receiving danazol/gestrinone, there was a significant difference in percentage
      change of BMD after six months of treatment, the GnRH analogue producing a
      reduction in BMD from baseline and danazol producing an increase in BMD (SMD 
      3.43, 95 % CI -3.91 to -2.95). Progesterone only add-back is not protective;
      after six months of treatment absolute value BMD measurements of the lumbar spine
      did not differ significantly from the group receiving GnRH analogues (SMD 0.15,
      95 % CI -0.21 to 0.52). In the comparison of GnRHa versus GnRHa + HRT add-back,
      that is oestrogen + progesterone or oestrogen only, there was a significantly
      bigger BMD loss in the GnRHa only group (SMD -0.49, 95 % CI -0.77 to -0.21).
      These numbers reflect the absolute value measurements at the lumbar spine after
      six months of treatment. Due to the small number of studies in the comparison we
      are unable to conclude whether calcium-regulating agents are protective. No
      difference was found between low and high dose add-back regimes but again only
      one study was identified for this comparison. Only one study comparing GnRH
      analogues with placebo was identified, but the study gave no data. No studies
      comparing GnRH with the oral contraceptive pill (OCP) or progestagens were
      identified. REVIEWER'S CONCLUSIONS: Both danazol and progesterone + oestrogen add
      back have been shown to be protective of BMD, while on treatment and up to six
      and 12 months later, respectively. However, by 24 months of follow-up there was
      no difference in BMD in those women who had HRT add-back. Studies of danazol
      versus GnRHa did not report long-term follow-up. The significant side effects
      associated with danazol limit its use.

PMID- 14583931
TI  - Lactational amenorrhea for family planning.
AB  - BACKGROUND: 50 % of pregnancies are unwanted. For several reasons including
      difficulty in obtaining contraceptives, no or ineffective contraception is used
      to prevent these unwanted pregnancies. The Lactational Amenorrhoea Method(LAM)
      however is a contraceptive method available and accessible for many women.
      OBJECTIVES: To assess in fully breastfeeding women, staying amenorrheic, the
      efficacy of the Lactational Amenorrhoea Method as a contraceptive method. The
      efficacy of LAM, as defined in 1988 in Bellagio, was compared with alternative
      definitions of LAM; the outcomes were measured using pregnancy and menstruation
      life tables. SEARCH STRATEGY:  DATA SOURCES: MEDLINE searches from 1966 until
      2002 and EMBASE from 1988 until 2002; reference lists of studies and review
      articles; books related to LAM; published abstracts from breastfeeding,
      reproductive health, contraceptive conferences; and e-mail communication with
      coordinators of such studies. SELECTION CRITERIA: From 454 potentially relevant
      studies 154 investigated the risk of pregnancy during LAM or lactational
      amenorrhea. Two reviewers applied the following inclusion criteria: prospective
      study, cases and -if available- controls had to be sexually active, pregnancy had
      to be confirmed by physical examination or a pregnancy test. Life table
      menstruation rates and life table pregnancy rates were taken as endpoints.
      Thirteen publications, reporting on 9 intervention groups and 2 control groups,
      met the inclusion criteria and were included in this systematic review. Their
      quality was assessed. DATA COLLECTION AND ANALYSIS: Two reviewers independently
      extracted data, disagreements were resolved through discussion. Because of the
      heterogeneity of the included studies, the studies were analyzed using narrative
      methods. MAIN RESULTS: For the outcome two controlled studies of LAM users
      reported life table pregnancy rates at 6 months of 0.45 and 2.45 percent and 5
      uncontrolled studies of LAM users reported 0-7.5 percent. Life table pregnancy
      rates of women fully breastfeeding and amenorrheic but not using any
      contraceptive method were 0.88 in one study and 0.9-1.2 percent (95% CI 0. 0-2.4
      ) in a second study, depending on the definition of menstruation used. The life
      table menstruation rate at 6 months in all studies varied between 11.1-39.4
      percent. REVIEWER'S CONCLUSIONS: No clear difference in life table pregnancy
      rates was found between women using LAM and supported in doing so, and fully
      breastfeeding, amenorroic women not using any method. Because the length of
      lactation amenorrhoea of women using LAM is too different between populations
      studied, and population specific, it is uncertain whether LAM extends lactational
      amenorrhoea.

PMID- 14583932
TI  - Anti-spasticity agents for multiple sclerosis.
AB  - BACKGROUND: Spasticity is a common problem in MS patients causing pain, spasms,
      loss of function and difficulties in nursing care. A variety of oral and
      parenteral medications are available. OBJECTIVES: To assess the absolute and
      comparative efficacy and tolerability of anti-spasticity agents in multiple
      sclerosis (MS) patients. SEARCH STRATEGY: We searched the Cochrane MS Group
      trials register (June 2003), the Cochrane Central Register of Controlled Trials
      (CENTRAL) (Issue 2, 2003), MEDLINE (January 1966 to June 2003), EMBASE (January
      1988 to June 2003), bibliographies of relevant articles, personal communication,
      manual searches of relevant journals and information from drug companies.
      SELECTION CRITERIA: Double-blind, randomised controlled trials (either placebo
      controlled or comparative studies) of at least seven days duration. DATA
      COLLECTION AND ANALYSIS: Two independent reviewers extracted data and the
      findings of the trials were summarised. Missing data were collected by
      correspondence with principal investigators. A meta-analysis was not performed
      due to the inadequacy of outcome measures and methodological problems with the
      studies reviewed. MAIN RESULTS: Twenty-six placebo-controlled studies (using
      baclofen, dantrolene, tizanidine, botulinum toxin, vigabatrin, prazepam,
      threonine and cannabinoids) and thirteen comparative studies met the selection
      criteria and were included in this review. Only fifteen of these studies used the
      Ashworth scale, of which only three of the eight placebo-controlled trials and
      none of the seven comparative studies showed a statistically significant
      difference between test drugs. Spasms, other symptoms and overall impressions
      were only assessed using unvalidated scores and results of functional assessments
      were inconclusive. REVIEWER'S CONCLUSIONS: The absolute and comparative efficacy
      and tolerability of anti-spasticity agents in multiple sclerosis is poorly
      documented and no recommendations can be made to guide prescribing. The rationale
      for treating features of the upper motor neurone syndrome must be better
      understood and sensitive, validated spasticity measures need to be developed.

PMID- 14583933
TI  - Inhaled long acting beta agonists for stable chronic asthma.
AB  - BACKGROUND: Asthma is a common respiratory disease among both adults and children
      and short acting inhaled beta-2 agonists are used widely for 'reliever'
      bronchodilator therapy. Long acting beta-2 agonists were introduced as
      prospective 'symptom controllers' in addition to inhaled corticosteroid
      'preventer' therapy (ICS). OBJECTIVES: This review aimed to determine the benefit
      or detriment on the primary outcome of asthma control with the regular use of
      long acting inhaled beta-2 agonists compared with placebo. SEARCH STRATEGY: We
      carried out searches using the Cochrane Airways Group trial register, most
      recently in October 2002. We searched bibliographies of identified RCTs for
      additional relevant RCTs and contacted authors of identified RCTs for other
      published and unpublished studies. SELECTION CRITERIA: All randomised studies of
      at least two weeks duration, comparing a long acting inhaled beta-agonist given
      twice daily with a placebo, in chronic asthma. DATA COLLECTION AND ANALYSIS: Two
      reviewers performed data extraction and study quality assessment independently.
      We contacted authors of studies for missing data. MAIN RESULTS: Eighty five
      studies met the inclusion criteria, 56 parallel group and 29 cross over design.
      Salmeterol xinafoate was used as long acting agent in 60 studies and formoterol
      fumarate in 25. The treatment period was two to four weeks in 32 studies, and 12
      to 52 weeks in 53 studies. 34 study groups used concurrent inhaled corticosteroid
      treatment, 21 studies did not permit their use and 35 permitted either inhaled
      corticosteroid or cromones. There were significant advantages to long acting beta
      2 agonist treatment compared to placebo for a variety of measurements of airway
      calibre including morning peak expiratory flow (PEF) (weighted mean difference
      (WMD) 26.78 L/min 95%CI 20.36 to 33.20), evening PEF (WMD 19.17 L/min 95%CI 11.63
      to 26.73). They were associated with significantly fewer symptoms, less use of
      rescue medication and higher quality of life scores. The risk of exacerbation was
      lower in adults using regular inhaled corticosteroids. REVIEWER'S CONCLUSIONS:
      Long acting beta-2 agonists are effective in the control of chronic asthma, and
      the evidence supports their use in addition to inhaled corticosteroids, as
      emphasised in current guidelines. Further research is needed on their use in
      children under 12 and in mild asthmatics not taking ICS.

PMID- 14583934
TI  - Prolonged antibiotics for purulent bronchiectasis.
AB  - BACKGROUND: The vicious cycle hypothesis for bronchiectasis predicts that
      bacterial colonisation of the respiratory tract perpetuates inflammatory change.
      This damages the mucociliary escalator preventing bacterial clearance and
      allowing the persistence of pro-inflammatory mediators. Conventional treatment
      with physiotherapy and intermittent antibiotics are felt to improve the condition
      of bronchiectasis patients although there are no conclusive data showing that
      these interventions influence the natural history of the condition. Various
      strategies have been tried to interrupt this cycle of infection and inflammation
      and one of these is to prolong antibiotic treatment in the hope of allowing the
      airway mucosa to heal. OBJECTIVES: This systematic review brings together the
      evidence and where possible presents a meta-analysis of the data available to
      answer the question 'Does treatment with prolonged courses of antibiotics
      influence the outcome in purulent bronchiectasis?' SEARCH STRATEGY: The Cochrane
      Airways Group trials register and reference lists of identified articles were
      searched. SELECTION CRITERIA: Randomised trials looking at the use of prolonged
      antibiotic therapy in the treatment of bronchiectasis. DATA COLLECTION AND
      ANALYSIS: Trial quality was assessed and data extraction was carried out by the
      reviewers independently. Study authors were contacted for missing information.
      MAIN RESULTS: 447 abstracts were found and reviewed for suitability. Six trials
      were included and 302 patients were randomised amongst these trials. 40% of the
      patients were contributed by one trial. Antibiotics were given for between 4
      weeks and one year. There were 40 withdrawals due to treatment failure and
      intolerable side effects. Only limited meta-analysis was possible due to the
      diversity of the trials. Response rates showed significant effects in favour of
      prolonged antibiotic treatment (Peto OR (95% CI), 3.37 (1.60 to 7.09)).
      Conversely for exacerbation rates there was no significant difference between
      prolonged antibiotics and placebo (Peto OR (95% CI), 0.96 (0.27 to 3.46)). For
      withdrawals there was no significant difference between treatment and placebo
      management (Peto OR (95% CI), 1.06 (0.42 to 2.65)). Data for lung function showed
      no significant benefit in favour of antibiotic treatment (% predicted FEV1, WMD
      (95% CI) -1.05 (-6.93 to 4.83)). REVIEWER'S CONCLUSIONS: The evidence available
      shows a small benefit for the use of prolonged antibiotics in the treatment of
      bronchiectasis. This review is limited by the diversity of the trials. Further
      randomised controlled trials with adequate power and standardised end points are
      required.

PMID- 14583935
TI  - Local oestrogen for vaginal atrophy in postmenopausal women.
AB  - BACKGROUND: Vaginal atrophy is a frequent complaint of postmenopausal women;
      symptoms include vaginal dryness, itching, discomfort and painful intercourse.
      Systemic treatment for these symptoms in the form of oral hormone replacement
      therapy is not always necessary. An alternative choice is oestrogenic
      preparations administered vaginally (in the form of creams, pessaries, tablets
      and the estradiol releasing ring). OBJECTIVES: The objective of this review is to
      compare the effectiveness, safety and acceptability of oestrogenic preparations
      for women who suffer from vaginal atrophy. SEARCH STRATEGY: We searched the
      Cochrane Menstrual Disorders and Subfertility Group register of trials (searched
      January 2003), The Cochrane Library (Issue 2, 2003), MEDLINE (1966-January 2003),
      EMBASE (1980-January 2003), Current Contents (1993-January 2003), Biological
      Abstracts (1969-2002), Social Sciences Index (1980-January 2003), PsycINFO (1972
      February 2003), CINAHL (1982-January 2003) and reference list of articles. We
      also contacted manufacturers and researchers in the field. SELECTION CRITERIA:
      The inclusion criteria were randomised comparisons of oestrogenic preparations
      administered intravaginally in postmenopausal women for the treatment of symptoms
      resulting from vaginal atrophy or vaginitis. DATA COLLECTION AND ANALYSIS: Twenty
      nine trials were identified, of these 13 were excluded. Trials were assessed for
      quality and two reviewers extracted data independently. Ratios for dichotomous
      and means for continuous outcomes were estimated. Outcomes analysed were included
      under the headings of efficacy, safety and acceptability. MAIN RESULTS: Sixteen
      trials with 2129 women were included in this review. The overall quality of the
      studies was good, although not all trials measured the same outcomes. All trials
      measured efficacy with various outcome measures. When comparing efficacy of
      oestrogenic preparations (in the form of creams, pessaries, tablets and the
      estradiol releasing vaginal ring) with each other in relieving the symptoms of
      vaginal atrophy, results indicated significant differences favouring the cream,
      ring, and tablets when compared to placebo and non-hormonal gel. Fourteen trials
      compared safety. Four looked at hyperplasia, four looked at endometrial
      overstimulation and six looked at adverse effects. One trial showed significant
      adverse effects of cream (conjugated equine oestrogen) when compared to tablets
      (estradiol) which included uterine bleeding, breast pain and perineal pain (1
      RCT; OR 0.18, 95% CI 0.07 to 0.50). Two trials showed significant endometrial
      overstimulation as evaluated by progestagen challenge test in the cream
      (conjugated equine oestrogen) group when compared to the ring (OR 0.29, 95% CI
      0.11 to 0.78). Although not statistically significant there was a 2% incidence of
      simple hyperplasia in the ring group when compared to cream (conjugated equine
      oestrogen) and 4% incidence of hyperplasia (one simple, one complex) in the cream
      group (conjugated equine oestrogen) when compared to the tablet (estradiol). Nine
      studies compared acceptability to the participants by comparing comfort of
      product, ease of use, overall product rating, delivery system and satisfaction.
      Results showed a significant preference for the estradiol releasing vaginal ring.
      REVIEWER'S CONCLUSIONS: Creams, pessaries, tablets and the estradiol vaginal ring
      appeared to be equally effective for the symptoms of vaginal atrophy. One trial
      found significant side effects noted following cream (conjugated equine
      oestrogen) administration when compared to tablets causing uterine bleeding,
      breast pain and perineal pain. Another trial found significant endometrial
      overstimulation following cream (conjugated equine oestrogen) when compared to
      the ring. As a treatment choice women appeared to favour the estradiol releasing
      vaginal ring for ease of use, comfort of product and overall satisfaction.

PMID- 14583936
TI  - Preoperative chemotherapy for resectable thoracic esophageal cancer.
AB  - BACKGROUND: Surgery has been the treatment of choice for localized esophageal
      cancer. A number of studies have investigated whether preoperative chemotherapy
      followed by surgery leads to an improvement in cure rates, but the individual
      reports have been conflicting. An explicit systematic update of the role of
      preoperative chemotherapy in the treatment of resectable thoracic esophageal
      cancer is therefore warranted. OBJECTIVES: The objective of this review is to
      determine the role of preoperative chemotherapy on patients with resectable
      thoracic esophageal carcinomas. SEARCH STRATEGY: Trials were identified by
      searching the Cochrane Controlled Trials Register, MEDLINE (1966 - 2003), EMBASE
      (1988 - 2003) and CancerLit (1993 - 2003). There were no language restrictions.
      SELECTION CRITERIA: Types of studies. Studies that randomised patients with
      potentially resectable carcinomas of the esophagus (of any histologic type) to
      chemotherapy or no chemotherapy before surgeries were included in this review.
      Types of participants. The participants consisted of patients with localized
      potentially resectable thoracic esophageal carcinomas. Trials involving patients
      with carcinomas of the cervical esophagus were excluded. Types of interventions.
      Trials that compared chemotherapy before surgery (esophagectomy) with surgical
      resections alone (esophagectomy) were included. Types of outcome measures. The
      primary outcome was overall survival at yearly intervals after randomisation.
      Secondary outcomes of interest included rates of resections, response to
      chemotherapy, rates of local and distant recurrences, quality-of-life, and
      treatment morbidity and mortality. DATA COLLECTION AND ANALYSIS: All analyses
      were carried out on intention-to-treat. Survival at 1, 2, 3, 4 and five years
      were used as endpoints of clinical relevance along with the median survival. The
      risk ratio (relative risk; RR) was the primary measure of effect for survival,
      rates of resections, and tumour recurrences. The risk difference (RD) was used to
      describe differences in response to chemotherapy, treatment morbidity and
      mortality. MAIN RESULTS: There were 11 randomised trials involving 2051 patients.
      At 1- year and 2-year the risk ratios showed no difference in survival between
      preoperative chemotherapy and surgery alone. The 3-year risk ratios found a 21%
      increase in survival (RR = 1.21; 95% CI 0.88 to 1.68; p = 0.25) and a 24%
      increase in survival with preoperative chemotherapy at 4 years (RR = 1.24; 95% CI
      0.92 to 1.68; p = 0.15) but they did not reach statistical significance. Only at
      5 years did the results become significant (RR = 1.44; 95% CI 1.05 to 1.97; p =
      0.02). The overall rate of resections and the rate of complete resections (R0)
      did not differ between the preoperative chemotherapy arm and surgery alone. The
      pooled clinical response to chemotherapy was about 36% (RD = 0.36; 95% CI 0.26 to
      0.47) but the complete pathologic response was a disappointing 3% (RD = 0.03; 95%
      CI 0.01 to 0.04). No single agent or combination of chemotherapeutic agents was
      found to be superior to the others. There was a 19% reduction in local recurrence
      with preoperative chemotherapy, but this was not significant (RR = 0.81; 95% CI
      0.54 to 1.22; p = 0.3). Preoperative chemotherapy was somewhat more harmful to
      patients than surgery alone. REVIEWER'S CONCLUSIONS: In summary, preoperative
      chemotherapy plus surgery appears to offer a survival advantage at 3, 4, and 5
      years, which reached significance only at 5 years compared to surgery alone for
      resectable thoracic esophageal cancer of any histologic type. The number needed
      to treat for one extra survivor at five years is eleven patients. The results are
      tempered by the increased toxicity and mortality associated with chemotherapy.
      The most beneficial chemotherapy combination appears to be cisplatin and 5
      flurouracil based, however, the dosing is unclear.

PMID- 14583937
TI  - Conjugate vaccines for preventing Haemophilus influenzae type b infections.
AB  - BACKGROUND: Haemophilus influenzae (H. influenzae) is an important cause of
      meningitis and pneumonia in children, causing an estimated three million cases of
      serious disease and hundreds of thousands of deaths annually worldwide. The
      introduction of H. influenzae type b (Hib) vaccines into routine immunisation
      schedules in developed countries has been followed by a rapid decline in disease
      occurrence, but vaccine cost is a significant barrier to use in developing
      countries. There is a need to determine the size of the effects of the vaccine,
      to enable cost-effectiveness comparisons with competing priorities in developing
      countries. OBJECTIVES: 1. To determine the effects of conjugate Hib vaccine in
      preventing Hib disease or death in children under five years.2. To determine any
      serious adverse outcomes. SEARCH STRATEGY: Searches of the Cochrane Central
      Register of Controlled Trials (CENTRAL) (issue 1, 2003); MEDLINE (January 1966 to
      April 2003), EMBASE (1990 to April 2003); and scanning of reference lists and
      contacting of authors of trial reports. Reports in all languages were considered.
      SELECTION CRITERIA: All randomised controlled trials or quasi-randomised trials
      of conjugate H. influenzae type b vaccines compared with placebo or no treatment
      in children who were followed until at least two years of age. DATA COLLECTION
      AND ANALYSIS: Two investigators independently selected eligible studies and
      extracted data. Differences were resolved by discussion. MAIN RESULTS: Five
      studies were included in the review, and four in meta-analyses. The overall
      quality of the trials was good. The relative risk for invasive Hib disease was
      0.20 (95% confidence interval 0.07 to 0.54; random effects model), but there was
      statistically significant unexplained variation (heterogeneity) in the effects of
      the four trials in the meta-analysis (p = 0.002). The size of the effects found
      in the trials did not appear to differ consistently with different vaccine types,
      the number of vaccine doses, age at first vaccination or use in developed vs
      developing countries, but the confidence intervals for the effect estimates were
      wide.Hib-related mortality data showed a non-significant trend towards benefit
      (relative risk was 0.29; 95% confidence interval 0.07 to 1.20; random effects
      model). The relative risk for all cause mortality in the single trial from which
      data were available was 1.01 (95% confidence interval 0.38 to 2.67, random
      effects model). No serious adverse effects were reported in any of the trials,
      involving a total of 257,000 infants. REVIEWER'S CONCLUSIONS: Hib vaccine is safe
      and effective. The size of the effect could plausibly be anywhere between a 46%
      and 93% reduction in Hib invasive disease, before the effect of herd immunity is
      taken into account. In resource-poor settings, decisions to use the vaccine will
      depend on its cost, the local burden of Hib disease and competing priorities.
      Insufficient evidence from randomised controlled trials was identified of the
      effects of Hib conjugate vaccine on either Hib-specific or on all-cause
      mortality.

PMID- 14583938
TI  - Nonsteroidal anti-inflammatory drugs for primary dysmenorrhoea.
AB  - BACKGROUND: Dysmenorrhoea is a common gynaecological complaint consisting of
      painful cramps accompanying menstruation, which in the absence of any underlying
      abnormality is known as primary dysmenorrhoea. Research has shown that women with
      dysmenorrhoea have high levels of prostaglandins, hormones known to cause
      cramping abdominal pain. Nonsteroidal anti-inflammatory drugs (NSAIDs) are drugs
      which act by blocking prostaglandin production. OBJECTIVES: The purpose of this
      review is to compare all nonsteroidal anti-inflammatory drugs used in the
      treatment of primary dysmenorrhoea with placebo, with paracetamol and with each
      other to evaluate their effectiveness and safety. SEARCH STRATEGY: We searched
      the Cochrane Menstrual Disorders and Subfertility Group trials register (11 April
      2003), Cochrane Central Register of Controlled Trials (1st quarter 2003), MEDLINE
      (1966-April 2003), and EMBASE (1980 - Week 15 2003). Attempts were also made to
      identify trials from the National Research Register and the Clinical Trials
      Register. Citation lists of relevant publications, review articles, abstracts of
      major scientific meetings and included studies were also searched. SELECTION
      CRITERIA: All randomised controlled comparisons of NSAID therapies versus
      placebo, versus other NSAIDs or versus paracetamol when used to treat primary
      dysmenorrhoea. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed
      trials for quality and extracted data, calculating odds ratios for dichotomous
      outcomes and weighted mean differences for continuous outcomes. Crossover trial
      data were presented in additional tables and other data were summarised
      descriptively. MAIN RESULTS: In women with dysmenorrhoea, NSAIDs were found
      significantly more effective for pain relief than placebo (OR 7.91, 95% CI 5.65
      to 11.09), though overall adverse effects were also significantly more common (OR
      1.52 95% CI 1.09 to 2.12). When NSAIDs were compared with each other or with
      paracetamol, there was little evidence of the superiority of any individual NSAID
      with regard to either efficacy or safety. However the available evidence had
      little power to detect such differences, as most individual comparisons were
      based on very few small trials, most of which were unsuitable for meta-analysis.
      REVIEWER'S CONCLUSIONS: NSAIDs are an effective treatment for dysmenorrhoea,
      though women using them need to be aware of the significant risk of adverse
      effects. There is insufficient evidence to determine which (if any) individual
      NSAID is the most safe and effective for the treatment of dysmenorrhoea.

PMID- 14583939
TI  - Developmental care for promoting development and preventing morbidity in preterm
      infants.
AB  - BACKGROUND: Preterm infants experience a range of morbidity related to the
      immaturity of their organ systems and to concurrent disease states. An
      unfavourable environment in the neonatal intensive care unit (NICU) may compound
      this morbidity. Modification of the environment could minimize the iatrogenic
      effects. Developmental care is a broad category of interventions designed to
      minimize the stress of the NICU environment. These interventions may include one
      or more elements such as control of external stimuli (vestibular, auditory,
      visual, tactile), clustering of nursery care activities, and positioning or
      swaddling of the preterm infant. Individual strategies have also been combined to
      form programs, such as the 'Neonatal Individualized Developmental Care and
      Assessment Program' (NIDCAP) (Als 1986). OBJECTIVES: In preterm infants, do
      developmental care interventions reduce neurodevelopmental delay, poor weight
      gain, length of hospital stay, length of mechanical ventilation, physiological
      stress and other clinically relevant adverse outcomes? SEARCH STRATEGY: The
      Neonatal Review Group search strategy was utilized. Searches were made of MEDLINE
      from 1966 to July, 2003, and of CINAHL, The Cochrane Central Register of
      Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2003), and conference
      and symposia proceedings in the English language from 1990 to July, 2003. A list
      of all relevant articles was sent to two experts in the field to identify any
      omissions or additional unpublished studies. SELECTION CRITERIA: Randomized
      trials in which elements of developmental care are compared to routine nursery
      care for infants < 37 weeks gestation and that measured clinically relevant
      outcomes. Reports were in English or a language for which a translator was
      available. Computerized searches were conducted and all potentially relevant
      titles and abstracts were extracted. Retrieved articles were assessed for
      relevance independently by two reviewers, based on predetermined criteria.
      Articles that met all criteria for relevance were assessed for methodological
      quality based on predetermined criteria. Articles judged to have the appropriate
      quality by both reviewers were included in the analysis. DATA COLLECTION AND
      ANALYSIS: Data were extracted independently by the two authors. Meta-analyses
      were conducted for each intervention where the same outcome measures and/or
      instruments were used within comparable time points. MAIN RESULTS: This review
      detected 32 eligible randomized controlled trials involving four major groups of
      developmental care interventions, 19 sub-groups and multiple clinical outcomes.
      The results of the review indicate that developmental care interventions
      demonstrate some benefit to preterm infants with respect to: improved short-term
      growth and feeding outcomes, decreased respiratory support, decreased length and
      cost of hospital stay, and improved neurodevelopmental outcomes to 24 months
      corrected age. These findings were based on two or three small trials for each
      outcome, and did not involve meta-analyses of more than two trials for any one
      outcome. Although a number of other benefits were demonstrated, those results
      were from single studies with small sample sizes. The lack of blinding of the
      assessors was a significant methodological flaw in half of the studies. The cost
      of the interventions and personnel was not considered in any of the studies.
      REVIEWER'S CONCLUSIONS: Because of the inclusion of multiple interventions in
      most studies, the determination of the effect of any single intervention is
      difficult. Although there is evidence of some benefit of developmental care
      interventions overall, and no major harmful effects reported, there were a large
      number of outcomes for which no or conflicting effects were demonstrated. The
      single trials that did show a significant effect of an intervention on a major
      clinical outcome were based on small sample sizes, and the findings were often
      not supported in other small trials. Before a clear direction for practice can be
      supported, evidence demonstrating more consistent effects of developmental care
      interventions on important short- and long-term clinical outcomes is needed. The
      economic impact of the implementation and maintenance of developmental care
      practices should be considered by individual institutions.

PMID- 14583940
TI  - Cell salvage for minimising perioperative allogeneic blood transfusion.
AB  - BACKGROUND: Concerns regarding the safety of transfused blood, have prompted
      reconsideration of the use of allogeneic (blood from an unrelated donor) red
      blood cell (RBC) transfusion, and a range of techniques to minimise transfusion
      requirements. OBJECTIVES: To examine the evidence for the efficacy of cell
      salvage in reducing allogeneic blood transfusion and the evidence for any effect
      on clinical outcomes. SEARCH STRATEGY: Articles were identified by: computer
      searches of MEDLINE, EMBASE, Current Contents (to July 2002), the Cochrane
      Controlled Trials Register (Issue 2, 2002) and websites of international health
      technology assessment agencies. References in the identified trials and review
      articles were searched and authors contacted to identify additional studies.
      SELECTION CRITERIA: Controlled parallel group trials in which adult patients,
      scheduled for non-urgent surgery, were randomised to cell salvage, or to a
      control group, who did not receive the intervention. DATA COLLECTION AND
      ANALYSIS: Trial quality was assessed using criteria proposed by Schulz et al.
      (Schulz 1995) and Jadad et al. (Jadad 1996). Main outcomes measured were: the
      number of patients exposed to allogeneic red cell transfusion, and the amount of
      blood transfused. Other outcomes measured were: re-operation for bleeding, blood
      loss, post-operative complications (thrombosis, infection, non-fatal myocardial
      infarction, renal failure), mortality, and length of hospital stay (LOS). MAIN
      RESULTS: Overall, the use of cell salvage reduced the rate of exposure to
      allogeneic RBC transfusion by a relative 40% (relative risk [RR] = 0.60: 95%
      confidence interval [CI] = 0.51 to 0.70). The absolute reduction in risk (ARR) of
      receiving an allogeneic RBC transfusion was 23% (95%CI = 16% to 30%). In
      orthopaedic procedures the relative risk (RR) of exposure to RBC transfusion was
      0.42 (95%CI = 0.32 to 0.54) compared to 0.78 (95%CI = 0.68 to 0.88) for cardiac
      procedures. The use of cell salvage resulted in an average saving of 0.64 units
      of allogeneic RBC per patient (weighted mean difference [WMD] = -0.64: 95%CI = 
      0.86 to -0.46). Cell salvage did not appear to impact adversely on clinical
      outcomes. REVIEWER'S CONCLUSIONS: The results suggest cell salvage is efficacious
      in reducing the need for allogeneic red cell transfusion in adult elective
      surgery. However, the methodological quality of trials was poor. As the trials
      were unblinded and lacked adequate concealment of treatment allocation,
      transfusion practices may have been influenced by knowledge of the patient's
      treatment status biasing the results in favour of cell salvage.

PMID- 14583941
TI  - Effect(s) of assisted hatching on assisted conception (IVF & ICSI).
AB  - BACKGROUND: Failure of implantation and thus conception might result from
      inability of the blastocyst to escape from its zona pellucida. Artificial
      disruption of this coat has been proposed as a method of improving the success of
      assisted conception. OBJECTIVES: To determine whether assisted hatching of
      embryos facilitates live births, clinical pregnancy and implantation and whether
      it impacts on negative outcomes (such as miscarriage). SEARCH STRATEGY: We
      searched the Cochrane Menstrual Disorders and Subfertility Group trials register
      (26 November 2002), the Cochrane Controlled Trials Register (Cochrane Library
      Issue 2, 2002), MEDLINE (1996 to February 2003), EMBASE (1980 to February 2003)
      and reference lists of articles. Authors were contacted for missing and/or
      unpublished data. SELECTION CRITERIA: Trials were identified and independently
      screened by two reviewers. Randomised controlled trials of AH (mechanical,
      chemical or laser disruption of the zona pellucida prior to embryo replacement)
      versus no AH that reported live birth, clinical pregnancy or implantation rates
      were included. DATA COLLECTION AND ANALYSIS: Qualitative assessments and data
      extraction were performed independently by two reviewers. Outcomes were extracted
      as rates and combined using random effects meta-analysis, sensitivity analysis,
      subgrouping and meta-regression where appropriate. MAIN RESULTS: Twenty-three
      randomised controlled trials (2572 women) were included. There was no significant
      difference in the odds of live births in the AH compared with control groups (6
      RCTs; OR 1.21, 95% CI 0.82 to 1.78; 161 births from 523 women). Women undergoing
      assisted hatching were significantly more likely to achieve clinical pregnancy
      (722 clinical pregnancies in 2175 women, OR 1.63, 95% CI 1.27 to 2.09), however
      the studies were heterogeneous. Implantation data were difficult to analyse due
      to the practice of replacing multiple embryos in individual women. The trials
      provided insufficient data to investigate the impact of assisted hatching on
      several important outcomes, including monozygotic twinning, embryo damage,
      congenital and chromosomal abnormalities, and in vitro blastocyst development.
      REVIEWER'S CONCLUSIONS: There is insufficient evidence to determine any effect of
      AH on the 'take-home-baby rate' of assisted conception. There are also very few
      data regarding miscarriage rates and other adverse events. This prevents us from
      extrapolating the impact of AH on live births from our finding of improved odds
      of clinical pregnancy.

PMID- 14583942
TI  - Extended versus limited lymph nodes dissection technique for adenocarcinoma of
      the stomach.
AB  - BACKGROUND: Surgeons disagree about the merits and risks of radical lymph node
      clearance during gastrectomy for cancer. OBJECTIVES: To evaluate survival and
      peri-operative mortality after limited or extended lymph node removal during
      gastrectomy for cancer. SEARCH STRATEGY: We searched MEDLINE, EMBASE, CancerLit,
      LILACS, Central Medical Journal Japanese Database and the Cochrane register,
      references from relevant articles and conference proceedings. We contacted known
      workers in the field. SELECTION CRITERIA: Studies published after 1970 which
      reported 5 year survival or postoperative mortality rates, and clearly defined
      the node dissection performed, were considered. We excluded studies which overtly
      included patients receiving perioperative chemotherapy, and comparisons with
      clear systematic treatment allocation bias. Randomised controlled trials (RCTs),
      non-randomised comparisons and observational studies were considered separately.
      DATA COLLECTION AND ANALYSIS: Three reviewers selected trials for inclusion.
      Quality assessment and data extraction were performed independently by two
      reviewers. Results of trials of similar design were pooled. Meta-analysis was
      performed separately for randomised and non-randomised comparisons. MAIN RESULTS:
      Two randomised and two non-randomised comparisons of limited (D1) versus extended
      (D2) node dissection and 11 cohort studies of either D1 or D2 resection were
      analysed. Meta-analysis of randomised trials did not reveal any survival benefit
      for extended lymph node dissection (Risk ratio = 0.95 (95% CI 0.83 - 1.09), but
      showed increased postoperative mortality (RR 2.23, 95% CI 1.45 - 3.45). Pre
      specified subgroup analysis suggested a possible benefit in stage T3+ tumours (RR
      = 0.68, 95% CI 0.42-1.10). Non-randomised comparisons showed no significant
      survival benefit for extended dissection (RR 0.92, 95% CI 0.83 -1.02), but
      decreased mortality (RR 0.65, 95% CI 0.45-0.93). Subgroup analysis showed
      apparent benefit in UICC stage II and IIIa. Observational studies of D2 resection
      reported much better mortality and survival than those of D1 surgery, but the
      settings were strikingly different. REVIEWER'S CONCLUSIONS: D2 dissection carries
      increased mortality risks associated with spleen and pancreas resection, and
      probably with inexperience and low case volumes. Randomised studies show no
      evidence of overall survival benefit, but possible benefit in T3+ tumours. These
      results may be confounded by surgical learning curves and poor surgeon
      compliance. Non-randomised comparisons suggest a possible survival benefit for D2
      in intermediate UICC stages. Observational studies show high 5 year survival and
      low operative mortality after D2 dissection in experienced units, and poor
      results after D1 dissection in non-specialist units. Further studies, with
      precautions to eliminate learning curve effects, contamination and non
      compliance, are needed to evaluate D2 dissection in intermediate stage gastric
      cancer.

PMID- 14583943
TI  - Chemotherapy versus best supportive care for extensive small cell lung cancer.
AB  - BACKGROUND: Combination chemotherapy has been the mainstay of treatment for
      extensive stage small cell lung cancer (SCLC) over the last 25 years even though
      it only gives a short prolongation in median survival time. The main goal for
      these patients, if their survival prognosis is limited, should be adequate
      palliation with the aim of improving their quality of life. OBJECTIVES: To
      evaluate the effectiveness of chemotherapy in extensive SCLC compared with best
      supportive care (BSC) or placebo treatment. SEARCH STRATEGY: Medline (1966-Jan
      2003), Embase (1974-Jan 2003), Cancerlit (1993-Jan 2003) and the Cochrane Central
      Register of Controlled Trials (CENTRAL, Issue 4, 2002) were searched. In addition
      experts in the field were contacted to identify further studies not found by
      electronic searches. SELECTION CRITERIA: Randomised controlled trials in which
      any chemotherapy treatment was compared with a placebo group or best supportive
      care in patients with extensive stage SCLC. DATA COLLECTION AND ANALYSIS: Data
      extraction and quality assessment were undertaken independently by two reviewers
      and disagreements were resolved by a third author. Additional information on the
      included studies was obtained from the author of the original studies. MAIN
      RESULTS: Only two studies (the first published in 1977 and the second in 1982)
      met the inclusion criteria of the review. A total of 65 patients with extensive
      disease (33 in the first study and 32 in the second) were randomised to received
      either placebo treatment or ifosfamide. In the second study a third arm of
      comparison included ifosfamide plus CCNU. Ifosfamide gave an extra 78.5 days
      survival (mean survival time) compared with the placebo group. Partial tumour
      response was greater with the active treatment. Toxicity was only seen in the
      chemotherapy group. Pooled analysis was not possible because only mean survival
      time was reported in both studies for patients with extensive disease. REVIEWER'S
      CONCLUSIONS: Chemotherapeutic treatment prolongs survival in comparison with
      placebo in patients with advanced SCLC. Nevertheless the impact of chemotherapy
      on quality of life and in patients with poor prognosis is unknown. Well-designed,
      controlled trials are needed to further evaluate the risks and benefits of
      different chemotherapeutic schedules in patients with advanced small cell lung
      cancer.

PMID- 14583944
TI  - Psychological treatments for epilepsy.
AB  - BACKGROUND: Psychological interventions such as relaxation therapy, cognitive
      behaviour therapy, electroencephalogram (EEG) bio-feedback and educational
      interventions have been used alone or in combination in the treatment of
      epilepsy, to reduce the seizure frequency and improve the quality of life.
      OBJECTIVES: To assess whether the treatment of epilepsy with psychological
      methods is effective in reducing seizure frequency and/or leads to a better
      quality of life. SEARCH STRATEGY: We searched the Cochrane Epilepsy Group trial
      register (11 June 2003), the Cochrane Central Register of Controlled Trials (The
      Cochrane Library issue 2, 2003), MEDLINE (on 11 June 2003) and cross references
      from identified publications. SELECTION CRITERIA: Randomized or quasi-randomized
      studies assessing one or more types of psychological or behaviour modification
      techniques for people with epilepsy. DATA COLLECTION AND ANALYSIS: Two reviewers
      independently assessed the trials for inclusion and extracted data. Primary
      analyses were by intention to treat. Outcomes included reduction in seizure
      frequency and quality of life. MAIN RESULTS: We found three small trials (50
      participants) of relaxation therapy. They were of poor methodological quality and
      a meta-analysis was therefore not undertaken. No study found a significant effect
      of relaxation therapy on seizure frequency. One trial found cognitive behavioural
      therapy to be effective in reducing depression, among people with epilepsy with a
      depressed affect, whilst another did not. One trial of group cognitive therapy
      found no significant effect on seizure frequency. Two trials of combined
      relaxation and behaviour therapy and one of EEG bio-feedback and four of
      educational interventions did not provide sufficient information to assess their
      effect on seizure frequency. Combined use of relaxation and behaviour
      modification was found beneficial for anxiety and adjustment in one study. In one
      study EEG bio-feedback was found to improve the cognitive and motor functions in
      individuals with greatest seizure reduction. Educational interventions were found
      to be beneficial in improving the knowledge and understanding of epilepsy, coping
      with epilepsy, compliance to medication and social competencies. REVIEWER'S
      CONCLUSIONS: In view of methodological deficiencies and limited number of
      individuals studied, we have found no reliable evidence to support the use of
      these treatments and further trials are needed.

PMID- 14583945
TI  - Three- or four- versus two-drug antiretroviral maintenance regimens for HIV
      infection.
AB  - BACKGROUND: Combination antiretroviral therapy administered to HIV-infected
      individuals has been shown to decrease viral replication, improve immunologic
      function and delay the progression of HIV infection. However, because patient
      adherence to complicated combination-therapy antiretroviral regimens is difficult
      and because of concerns regarding the cumulative toxicity of antiretroviral
      drugs, regimens that utilize fewer antiretroviral agents are desirable.
      OBJECTIVES: To compare the use three- or four- versus two-drug antiretroviral
      maintenance regimens following successful initial therapy for HIV infection.
      SEARCH STRATEGY: The following electronic databases were searched for relevant
      randomized trials or reviews: 1. MEDLINE for the years 1982-May 2003 using the
      search terms human immunodeficiency virus, antiretroviral therapy, maintenance
      therapy, zidovudine, lamivudine, indinavir, stavudine, saquinivir, nelfinavir,
      didanosine, zalcitabine, ritonovir, AIDS, anti-HIV agents, HIV infection and HIV
      seropositivity. 2. AIDSLINE for the years 1982- May 2003 using the search terms
      antiretroviral therapy, maintenance therapy, zidovudine, lamivudine, indinavir,
      stavudine, saquinivir, nelfinavir, didanosine, zalcitabine, ritonovir, anti-HIV
      agents. 3. The Cochrane Database of Systematic Reviews, Database of Abstracts of
      Reviews of Effectiveness and the Cochrane Clinical Trials Register in the
      Cochrane Library, through May 2003. 4. AIDSTRIALS, a specialist registry of
      current and completed trials maintained by the U.S. National Library of Medicine
      through May 2003. The abstracts of relevant conferences, including the
      International Conferences on AIDS, the Conference on Retroviruses and
      Opportunistic Infections, the Infectious Disease Society of America annual
      meeting and the Interscience Conference on Antimicrobial Agents and Chemotherapy,
      as indexed by AIDSLINE, were also reviewed. Reference lists of all review
      articles and primary articles identified were also searched. SELECTION CRITERIA:
      Randomized controlled trials in which HIV-infected adults who had successfully
      completed initial three- or four-drug antiretroviral therapy were randomized to
      maintenance therapy with three or four drugs or maintenance therapy with two
      drugs. Successful initial therapy was defined by a plasma viral load of less than
      500 copies/ml. DATA COLLECTION AND ANALYSIS: Two reviewers assessed eligibility
      and trial quality. Attempts were made to contact the authors of the included
      abstract. Data on the number of patients experiencing loss of viral suppression
      were abstracted by two reviewers. The data were pooled, where appropriate, to
      yield odds ratios, using random effects models. MAIN RESULTS: Four trials were
      identified including three published studies and one abstract. Compared to three-
      or four-drug maintenance therapy, maintenance therapies including fewer drugs
      were associated with a higher risk of virologic failure (loss of HIV suppression
      to non-detectable levels). Combining the results of all four studies yielded an
      odds ratio of 5.55 (95% confidence interval, 3.14 - 9.80). Similar results were
      obtained when the one abstract was excluded (odds ratio, 5.48; 95% confidence
      interval, 2.82 - 10.65). Performing subgroup analyses of studies using similar
      induction and maintenance regimens gave similar results. Maintenance regimens of
      zidovudine and lamivudine compared to maintenance regimens with zidovudine,
      lamivudine and indinavir, were associated with significantly higher rates of
      virologic failure (odds ratio, 4.57; 95% confidence interval, 1.80 - 11.58).
      Similarly, maintenance regimens that discontinued one or more protease inhibitor
      after including them in induction therapy were also associated with a
      significantly higher risk of virologic failure (odds ratio, 6.15; 95% confidence
      interval, 3.40 -11.10). REVIEWER'S CONCLUSIONS: Although it is desirable to
      reduce the number of antiretroviral drugs given in combination therapy for
      reasons of compliance and toxicity, maintenance regimens with fewer drugs are
      associated with significantly increased resistance and risk of loss of viral
      suppression. Successful initial therapy, as evidenced by suppression of viral
      load, should not be modified in the maintenance phase unless clinically
      necessary.

PMID- 14583946
TI  - Organisational infrastructures to promote evidence based nursing practice.
AB  - BACKGROUND: The purpose of this systematic review is to determine to what extent
      organisational infrastructures are effective in promoting the implementation of
      high quality research evidence on the effectiveness of nursing interventions.
      OBJECTIVES: To identify and summarize rigorous evaluations of organisational
      infrastructure developments aimed at promoting evidence based nursing practice.
      SEARCH STRATEGY: We searched: The Cochrane Library, MEDLINE, EMBASE, CINAHL,
      SIGLE, HEALTHLINE, National Research Register, Nuffield Database of Health
      Outcomes, NIH Databases up to August 2002. We hand searched the Journal of
      Advanced Nursing, Applied Nursing Research and Journal of Nursing Administration
      (to 1999), and checked the reference lists of articles obtained. We contacted
      experts in the field and relevant Internet groups. SELECTION CRITERIA: Randomized
      controlled trials, controlled clinical trials and interrupted times series
      studies of an entire or identified component of an organisational infrastructure
      development aimed at promoting effective nursing interventions. The participants
      were health care organisations comprising nurses, midwives and health visitors in
      hospital and community settings. DATA COLLECTION AND ANALYSIS: All identified
      papers were screened independently for relevance, design and outcome by two
      reviewers. MAIN RESULTS: No studies were sufficiently rigorous to be included in
      this systematic review. Seven case study evaluations were identified but excluded
      from the review because of poor design and lack of controls. REVIEWER'S
      CONCLUSIONS: 1. There are no clear implications for practice.2. Several
      conceptual models on organisational processes to promote evidence based practice
      have been described in published papers, and a number of organisational
      infrastructural interventions have been described in published papers. None have
      been evaluated properly. The next step in this field should be to conduct well
      planned evaluations of well planned interventions. 3. Interrupted and Complex
      Interrupted Times Series (ITS and CITS) designs should be adopted as a useful
      alternative to randomized controlled trials where such trials would be
      impractical. The health service cost of any infrastructure developments should be
      assessed in any evaluation. If possible, patient outcomes should be measured
      directly.

PMID- 14583947
TI  - Interventions for normal tension glaucoma.
AB  - BACKGROUND: Normal tension glaucoma is a clinical condition in which the optic
      nerve is pathologically excavated and the visual field is disturbed. Nevertheless
      it has been assumed that intraocular pressure plays a role in the progression of
      visual field defects in this disease, but other, mainly vascular factors, have
      been discussed as well. OBJECTIVES: The objective of this review is to assess the
      effects of medical and surgical treatments for normal tension glaucoma. SEARCH
      STRATEGY: Trials were identified from the Cochrane Central Register of Controlled
      Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group trials
      register), MEDLINE, EMBASE and BIOSIS Previews. Bibliographies of identified
      trials were searched to find additional trials. In addition, investigators and
      pharmaceutical companies were contacted. Date of last search: January 2001.
      SELECTION CRITERIA: This review includes randomised controlled trials in which
      medical or surgical interventions were compared to no treatment, placebo or other
      treatment in people with normal tension glaucoma. Two reviewers independently
      assessed the full text copies of the possibly relevant trials. Trial quality was
      assessed according to the methods set out in Section 6 of the Cochrane Reviewers'
      Handbook (Clarke 2000). DATA COLLECTION AND ANALYSIS: Data were extracted by two
      reviewers and results were compared for differences. Discrepancies were resolved
      by discussion. The heterogeneity of interventions, follow-up periods and outcomes
      did not allow for statistical combinations of the study results. MAIN RESULTS:
      According to the selection criteria on visual field loss, eight studies were
      included in this review. Only three studies focussed on patient relevant
      outcomes. In one trial a beneficial effect of lowering intraocular pressure was
      found, but only if data were corrected for cataract development. In two small
      studies a beneficial effect on visual field loss of brovincamine, a calcium
      antagonist was reported. REVIEWER'S CONCLUSIONS: In one study the effect of
      intraocular pressure lowering on visual field outcome was only significant when
      data were corrected for cataract development. The results for calcium antagonists
      are promising, but larger trials have to be performed. Studies that focussed on
      reduction of intraocular pressure or haemodynamic variables are not necessarily
      relevant for the outcome in people with normal tension glaucoma.

PMID- 14583948
TI  - Drugs for nocturnal enuresis in children (other than desmopressin and
      tricyclics).
AB  - BACKGROUND: Enuresis (bedwetting) is a socially stigmatising and stressful
      condition which affects around 15-20% of five year olds, and up to 2% of young
      adults. Although there is a high rate of spontaneous remission, the social,
      emotional and psychological costs to the children can be great. OBJECTIVES: To
      assess the effects of drugs other than desmopressin and tricyclics on nocturnal
      enuresis in children, and to compare them with other interventions. SEARCH
      STRATEGY: We searched the Cochrane Incontinence Group trials register. Date of
      the most recent search: December 2002. The reference list of a previous version
      of this review was also searched. SELECTION CRITERIA: All randomised trials of
      drugs (excluding desmopressin or tricyclics) for nocturnal enuresis in children
      were included in the review. Trials were eligible for inclusion if children were
      randomised to receive drugs compared with placebo, other drugs or other
      conservative interventions for nocturnal bedwetting. Trials focused solely on
      daytime wetting were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers
      independently assessed the quality of the eligible trials and extracted data.
      MAIN RESULTS: In 32 randomised controlled trials (25 new in this update), a total
      of 1225 out of 1613 children received an active drug other than desmopressin or a
      tricyclic. In all, 28 different drugs or classes of drugs were tested, but the
      trials were generally small or of poor methodological quality (five were quasi
      randomised and the remainder failed to give adequate details about the
      randomisation process). Although indomethacin and diclofenac were better than
      placebo during treatment, desmopressin was better than both of them, with less
      chance of adverse effects. There were no data regarding what happened after
      treatment stopped. Limited data suggested that an alarm was better than drugs
      during treatment. REVIEWER'S CONCLUSIONS: There was not enough evidence to judge
      whether the included drugs reduced bedwetting. There was limited evidence to
      suggest that desmopressin, imipramine and alarms were better than the drugs to
      which they were compared. In other reviews, desmopressin, tricyclics and alarm
      interventions have been shown to be effective.

PMID- 14583949
TI  - Treatments for symptomatic urinary tract infections during pregnancy.
AB  - BACKGROUND: Urinary tract infections, including pyelonephritis, are serious
      complications that can result in significant maternal and neonatal morbidity and
      mortality. There is a large number of drugs, and combination of them, available
      to treat urinary tract infections, most of them tested in non-pregnant women.
      Attempts to define the optimal antibiotic regimen for pregnancy has, therefore,
      been problematic. OBJECTIVES: The objective of this review was to try to
      determine, from the best available evidence from randomized control trials, which
      agent is most effective for the treatment of symptomatic urinary tract infections
      during pregnancy in terms of cure rates, recurrent infection, incidence of
      preterm delivery and premature rupture of membranes, admission to neonatal
      intensive care unit, need for change of antibiotic, and incidence of prolonged
      pyrexia. SEARCH STRATEGY: The Cochrane Pregnancy and Childbirth Group trials
      register (January 2003) and reference lists of articles were searched. SELECTION
      CRITERIA: All trials were considered where the intention was to allocate
      participants randomly to one of at least two alternative treatments for any
      symptomatic urinary tract infection. DATA COLLECTION AND ANALYSIS: Both reviewers
      assessed trial quality and extracted data. MAIN RESULTS: Eight studies were
      included, recruiting a total of 905 pregnant women. In most of the comparisons
      there were no significant differences between studied treatments with regard to
      cure rates, recurrent infection, incidence of preterm delivery and premature
      rupture of membranes, admission to neonatal intensive care unit, need for change
      of antibiotic and incidence of prolonged pyrexia. Only when cefuroxime and
      cephradine were compared, were there better cure rates (29/49 versus 41/52) and
      less recurrences (20/49 versus 11/52) in the cefuroxime group, but the sample
      size is insufficient to ensure that differences found in the effect of the drugs
      were real. REVIEWER'S CONCLUSIONS: Although antibiotic treatment is effective for
      the cure of urinary tract infections, there are insufficient data to recommend
      any specific treatment regimen for symptomatic urinary tract infections during
      pregnancy. All the antibiotics studied were shown to be very effective in
      decreasing the incidence of outcomes measured. Complications were very rare. All
      included trials had very small sample sizes to try to detect important
      differences between treatments. Future studies should evaluate the most promising
      antibiotics, in terms of class, timing, dose, acceptability, maternal and
      neonatal outcomes and costs.

PMID- 14583950
TI  - Cisapride treatment for gastro-oesophageal reflux in children.
AB  - BACKGROUND: Gastro-oesophageal reflux (GOR) is an extremely common and usually
      self-limiting condition in infants. When treatment is required, Cisapride, a pro
      kinetic agent, has been commonly prescribed for the symptomatic management of
      GOR. There have been recent reports of possibly serious adverse events, e.g. an
      increased QTc interval, cardiac arrhythmias, and death, associated with the use
      of Cisapride. OBJECTIVES: To determine the effectiveness of Cisapride for
      symptoms of GOR compared with placebo or any other non-surgical treatments.
      SEARCH STRATEGY: Searches were conducted of the Cochrane Central Trials Register
      and the specialised Trials register of the Cochrane Upper Gastrointestinal and
      Pancreatic Diseases Group, MEDLINE and Embase up till April 2002. Reference lists
      of relevant review articles and identified trials were scrutinised and forward
      citation searches were performed in the Science Citation Index on all trials
      identified. The search was re-run in August 2003 and no new trials were found.
      SELECTION CRITERIA: Randomised controlled trials that compared oral Cisapride
      therapy with placebo or with other non-surgical treatments for children with a
      diagnosis of GOR were included. Only studies in which Cisapride was administered
      orally for a minimum of one week and which documented at least one of the primary
      outcomes were included. We excluded trials in which the majority of participants
      were aged less than 28 days. DATA COLLECTION AND ANALYSIS: The primary outcomes
      were defined as a change in symptoms at the end of treatment, presence of adverse
      events, occurrence of clinical complications, and weight gain. The secondary
      outcomes included physiological measures of GOR or histological evidence of
      oesophagitis. We dichotomised symptoms into 'same or worse' vs 'improved' and
      calculated summary odds ratios. Continuous measures of GOR (e.g. reflux index)
      were summarised as a weighted mean difference. All outcomes were analysed using a
      random effects method. MAIN RESULTS: Searches identified nine trials which met
      the inclusion criteria. Eight trials compared Cisapride with placebo, of which
      seven (236 participants) reported data on symptoms of gastro-oesophageal reflux,
      and one reported data on the QTc interval (49 patients). The odds ratio for 'same
      or worse' vs 'improved symptoms' at the end of treatment of 0.34 (95%CI 0.10,
      1.19) did not show a statistically significant difference between the two
      interventions. There was significant heterogeneity between the studies and the
      funnel plot suggested publication bias. In a sensitivity analysis, the definition
      of outcomes was changed to 'any symptoms' vs 'no symptoms'. This resulted in the
      exclusion of three trials (one of them the largest, best quality trial). The
      resulting pooled odds ratio showed a significant effect of Cisapride (OR 0.19,
      95%CI 0.08, 0.44). Five studies reported adverse events. Four reported adverse
      events (mainly diarrhoea) but the difference was not statistically significant
      (OR 1.80, 95%CI 0.87, 3.70). One trial found no difference in the QTc after 3 to
      8 weeks of treatment. Cisapride was associated with a statistically significant
      reduction in the reflux index (weighted mean difference -6.49, 95%CI -10.13, 
      2.85), but as reflux index and clinical symptoms are poorly correlated, the
      clinical importance of this finding is uncertain. Other measures of oesophageal
      pH monitoring did not reach significance. One included study compared Cisapride
      with Gaviscon (or Gaviscon and Carobel). The odds ratio for 'same or worse' vs
      'improvement' in the Cisapride group compared with Gaviscon was 3.26 (95%CI 0.93
      11.38). REVIEWER'S CONCLUSIONS: We found no clear evidence that Cisapride reduces
      symptoms of GOR. The results suggested substantial publication bias favouring
      studies showing a positive effect of Cisapride. This finding is supported by the
      report of one unpublished multi-centre study of 134 patients, which was reported
      to show no evidence of a significant effect of Cisapride. Due to reports of fatal
      cardiac arrhythmias or sudden death, from July Due to reports of fatal cardiac
      arrhythmias or sudden death, from July 2000, cisapride was restricted to a
      limited access programme supervised by a paediatric gastrologist in the USA and
      in Europe, to patients treated within a clinical trial or safety study or
      registry programme.

PMID- 14583951
TI  - Mast-cell stabilising agents to prevent exercise-induced bronchoconstriction.
AB  - BACKGROUND: Exercise-induced bronchoconstriction (or asthma) following strenuous
      physical exertion is common and can cause sub-optimal performance, symptoms such
      as cough, dyspnea, wheeze, chest tightness, and can lead people to avoid physical
      activity. Management focuses on prevention with pre-exercise treatment using
      various pharmacologic agents. Mast cell stabilizing agents are effective in
      attenuating exercise-induced bronchoconstriction but their effectiveness compared
      to bronchodilator agents is unclear. OBJECTIVES: To quantitatively compare the
      effects of inhaling a single dose of either mast cell stabiliser - nedocromil
      sodium or sodium cromoglycate - to a single dose of short acting beta-agonists or
      anti-cholinergic agents - atropine or ipratropium bromide - prior to a strenuous
      exercise challenge in participants with asthma who are at least 6 years of age
      and suffer from reproducible exercise-induced bronchoconstriction. The review
      also compares the effects between a short acting beta-agonist alone to a
      combination of a short acting beta-agonist + mast cell stabiliser. SEARCH
      STRATEGY: We searched the Cochrane Airways Group ASTHMA and WHEEZ* trials
      register, Cochrane CENTRAL, Current Contents, review articles, textbooks and
      reference lists of articles. We also contacted the drug manufacturer and primary
      authors for additional citations. SELECTION CRITERIA: Randomised trials comparing
      a single prophylactic dose of a mast cell stabiliser to a short acting beta
      agonist, anti-cholinergic agent, or a short acting beta-agonist alone to a
      combination of short acting beta-agonist plus a mast cell stabiliser to prevent
      exercise-induced bronchoconstriction in asthmatics over six years old. The
      exercise challenge had to conform to acceptable standards and pulmonary function
      (PFT) reported as percent decrease from baseline of FEV1 or peak flow. Complete
      protection (maximum % fall PFT <15% post-exercise) and clinical protection (50%
      improvement over placebo effect) measures were included. DATA COLLECTION AND
      ANALYSIS: Trial inclusion and quality assessments were conducted independently by
      two reviewers using standardised forms. A second reviewer confirmed data
      extraction and calculations. Attempts were made to contact study authors. The
      pooled estimate involving continuous pulmonary function measures are reported as
      a weighted mean difference (WMD), dichotomous data as an odds ratio (OR), both
      with 95% confidence intervals (95%CI) using a random effects model. Heterogeneity
      tests for pooled results were performed. MAIN RESULTS: Twenty-four trials (518
      participants) conducted in 13 countries between 1976 and 1998 were included. All
      drugs were effective at attenuating the exercise-induced bronchoconstriction
      response but to varying degrees even within the same individual. Compared to anti
      cholinergic agents, mast cell stabilisers were somewhat more effective at
      attenuating bronchoconstriction. On average the maximum fall on MCS was reduced
      to 7.1% compared to 13.8% on AC ( WMD = 6.7%; 95% CI: 3.3 to 10.0), provided more
      individuals with complete protection (73% vs 56%; OR = 2.2; 95% CI: 1.3 to 3.7)
      and clinical protection (73% vs 52%; OR = 2.7; 95% CI: 1.1 to 6.4). There were no
      subgroup differences based on age, severity, or study quality, and no adverse
      effects were reported for either agent group. When compared to short acting beta
      agonists mast cell stabilisers were not as effective at preventing deterioration.
      On average the maximum fall on MCS was 11.2% compared to 4.3% on beta agonists (
      WMD = 6.8%; 95% CI: 4.5 to 9.2). MCS provided fewer individuals with complete
      protection (66% vs 85%; OR = 0.3; 95% CI: 0.2 to 0.5) or clinical protection (55%
      vs 77%; OR = 0.4; 95% CI: 0.2 to 0.8). There were no significant subgroup
      differences based on age, severity, drug, delivery, or study quality. A non
      significant difference in side effects was demonstrated with 11% of short acting
      beta-agonist patients experiencing side effects compared to 3% of those receiving
      mast cell stabilisers (OR = 0.2; 95% CI: 0.0 to 8.2). Combining masta-agonist
      patients experiencing side effects compared to 3% of those receiving mast cell
      stabilisers (OR = 0.2; 95% CI: 0.0 to 8.2). Combining mast cell stabilisers with
      a short acting beta-agonist did not produce significant advantages to pulmonary
      function over short acting beta-agonists alone. On average the maximum fall on
      SABA only was reduced to 5.3% compared to 3.5% on the combination ( WMD = 1.8%;
      95% CI: -1.1 to 4.6). Beta-agonists alone provided fewer individuals with
      complete protection (68% vs 80%; OR = 0.5; 95% CI: 0.2 to 1.4) or clinical
      protection (70% vs 86%; OR=0.4; 95% CI: 0.1 to 1.2) but the difference did not
      reach significance (p=0.17). There were no subgroup differences. REVIEWER'S
      CONCLUSIONS: In a population of stable asthmatics short acting beta-agonists,
      mast cell stabilisers, or anticholinergics will provide a significant protective
      effect against exercise-induced bronchoconstriction with few adverse effects. On
      average, SABAs resulted in more effective attenuation than mast cell stabilisers,
      while mast cell stabilisers were more effective than anti-cholinergic agents.
      Combining SABA and mast cell stabilisers may be appropriate in selected cases.
      The variability in the individual degree of response to these drugs in multi arm
      trials suggests clinicians and patients work together to identify the most
      effective prophylactic therapy.

PMID- 14583952
TI  - Drugs for preventing migraine headaches in children.
AB  - BACKGROUND: It has been estimated that about ten per cent of children between six
      and 20 years of age suffer from migraine. It is estimated that children with
      migraine lose one and a half weeks more schooling per year than their peers.
      Prophylactic drugs can be prescribed when children suffer from frequent or
      disabling headaches. OBJECTIVES: We aimed to describe and assess the evidence
      from controlled trials on the efficacy and tolerability of pharmacological agents
      taken on a regular basis to prevent the occurrence of migraine attacks and/or
      reduce the intensity of such attacks in children with migraine. SEARCH STRATEGY:
      The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE
      were searched from 1966 through 2002. Additional strategies for identifying
      trials included searching the reference lists of review articles and included
      studies and searching books related to headache. SELECTION CRITERIA: Prospective
      randomised controlled trials (RCTs) of self- or parent-administered drug
      treatments in children (under 18 years of age) who had received a diagnosis of
      migraine were included. DATA COLLECTION AND ANALYSIS: Two investigators
      extracted, assessed, and coded separately all data for each study, using a form
      that was designed specifically for the review. Any disagreement was resolved by
      discussion. Headache frequency standardised over 28 days was used as the primary
      outcome measure. Headache intensity, headache duration, amount of symptomatic
      treatment used, and headache indices were used as secondary outcome measures.
      Data were extracted from both parallel-group and crossover trials. Continuous and
      dichotomous data were used to calculate standardised mean differences (SMDs) and
      odds ratios (ORs), respectively. Numbers-needed-to-treat (NNTs) and numbers
      needed-to-harm (NNHs) were also calculated. MAIN RESULTS: Thirty-eight studies
      were selected. Eighteen were excluded. Eleven preventive drugs were compared with
      placebo in a total of 15 studies. Drug-drug comparisons were made in just six
      studies. For only four drugs (L-5-hydroxytryptophan [L-5HTP], flunarizine,
      clonidine, and propranolol) were two or more studies selected. For only six drugs
      (trazodone, L-5HTP, propranolol, flunarizine, papaverine, and nimodipine) were
      data reported for effect on frequency. For no individual drug were comparable
      data reported in more than one study, thus meta-analysis was not possible. Two
      placebo-controlled studies showed a beneficial effect on the primary outcome
      measure, headache frequency. They were for the drugs propranolol and flunarizine.
      The propranolol study reported a dichotomous outcome (proportion of children
      responding), and it was possible to calculate a number-needed-to-treat to produce
      a two-thirds reduction in headache frequency (NNT = 1.5, 95%CI 1.15 to 2.1). The
      flunarizine study produced a SMD of 1.51 (95% confidence interval, -2.21 to 
      0.82), which was statistically significant in favour of flunarizine (p < 0.001).
      Nimodipine, timolol, papaverine, pizotifen, trazodone, L-5HTP, clonidine,
      metoclopramide, and domperidone showed no efficacy in reduction of frequency of
      attacks. The available studies on cyproheptadine, phenobarbitone, phenytoin,
      amitriptyline, carbamazepine, metoprolol, and piracetam were excluded for various
      reasons. REVIEWER'S CONCLUSIONS: Only one study each for propranolol and
      flunarizine were identified showing efficacy of these drugs as prophylactics of
      paediatric migraine. Nimodipine, timolol, papaverine, pizotifen, trazodone, L
      5HTP, clonidine, metoclopramide, and domperidone showed no efficacy in reduction
      of frequency of attacks. Available studies on other commonly used drugs failed to
      meet our inclusion criteria. The quality of evidence available for the use of
      drug prophylaxis in paediatric migraine was poor. Studies were generally small,
      with no planning of sample size, so that for many drugs, despite the negative
      findings of this review, we do not have conclusive evidence of 'no effect'. There
      is a clear and urgent need for methodologically sound RCTs for the use of pings
      of this review, we do not have conclusive evidence of 'no effect'. There is a
      clear and urgent need for methodologically sound RCTs for the use of prophylactic
      drugs in paediatric migraine, starting with propranolol. These studies need to be
      adequately powered to investigate meaningful reductions in pain and suffering
      from a patient's perspective.

PMID- 14583953
TI  - Therapeutic touch for healing acute wounds.
AB  - BACKGROUND: Therapeutic Touch (TT) as a treatment modality has increased in
      popularity over the past two decades. Its efficacy in relation to the healing of
      wounds has been expounded in anecdotal publications. To date however there has
      been no systematic review. OBJECTIVES: To identify and review all relevant data
      to determine the effectiveness of TT in the promotion of wound healing. SEARCH
      STRATEGY: The Cochrane Wounds Group Specialised Trials Register and the Cochrane
      Central Register of Controlled Trials were searched in May 2003. The Cochrane
      Complementary Medicine field database was searched in September 2002. In addition
      the Sigma Theta Tau International Registry of Nursing Research (1983 to 2002) was
      also searched in September 2002. Furthermore searches of MEDLINE (1966 to 2003)
      were conducted in 1997 and May 2003, CINAHL (1982 to 2002) in September 2002 and
      dissertation abstracts in September 2002. SELECTION CRITERIA: All randomised or
      quasi-randomised controlled trials, which compared the effect of TT with a
      placebo, another treatment, or no treatment control were considered. Studies
      which used TT as a stand-alone treatment, or as an adjunct to other therapies,
      were eligible. DATA COLLECTION AND ANALYSIS: One reviewer (DO) determined the
      eligibility for inclusion of all trials. Both reviewers conducted data extraction
      and evaluation of each trial's quality independently. Each trial was analysed
      based on predetermined criteria and a narrative of each trial's main conclusions
      was produced. MAIN RESULTS: Four trials in people with experimental wounds were
      eligible for inclusion. The effect of TT on wound healing in these studies was
      variable. Two of the studies (n = 44 & 24) demonstrated a significant effect of
      TT. However the results of the two other trials favoured the control group (n =
      15 & 38), one of these trials demonstrated a significant effect in favour of the
      control group. REVIEWER'S CONCLUSIONS: There is insufficient evidence that TT
      promotes healing of acute wounds.

PMID- 14583954
TI  - Topical fluoride (toothpastes, mouthrinses, gels or varnishes) for preventing
      dental caries in children and adolescents.
AB  - BACKGROUND: Topical fluoride therapy (TFT) in the form of varnish, gel,
      mouthrinse or toothpaste has been used extensively as a caries-preventive
      intervention for over three decades. OBJECTIVES: To determine the effectiveness
      and safety of fluoride varnishes, gels, mouthrinses, and toothpastes in the
      prevention of dental caries in children and to examine factors potentially
      modifying their effect. SEARCH STRATEGY: We searched the Cochrane Oral Health
      Group's Trials Register (May 2000), CENTRAL (The Cochrane Library Issue 2, 2000),
      MEDLINE (1966 to January 2000), plus several other databases. We handsearched
      journals, reference lists of articles and contacted selected authors and
      manufacturers. SELECTION CRITERIA: Randomized or quasi-randomized controlled
      trials with blind outcome assessment, comparing fluoride varnish, gel,
      mouthrinse, or toothpaste with placebo or no treatment in children up to 16 years
      during at least 1 year. The main outcome was caries increment measured by the
      change in decayed, missing and filled tooth surfaces (D(M)FS). DATA COLLECTION
      AND ANALYSIS: Inclusion decisions, quality assessment and data extraction were
      duplicated in a random sample of one third of studies, and consensus achieved by
      discussion or a third party. Authors were contacted for missing data. The primary
      measure of effect was the prevented fraction (PF) that is the difference in mean
      caries increments between the treatment and control groups expressed as a
      percentage of the mean increment in the control group. Random effects meta
      analyses were performed where data could be pooled. Potential sources of
      heterogeneity were examined in random effects metaregression analyses. MAIN
      RESULTS: There were 144 studies included. For the 133 that contributed data for
      meta-analysis (involving 65,169 children) the D(M)FS pooled prevented fraction
      estimate was 26% (95% CI, 24% to 29%; p < 0.0001). There was substantial
      heterogeneity, confirmed statistically (p < 0.0001), but the direction of effect
      was consistent. The effect of topical fluoride varied according to type of
      control group used, type of TFT used, mode/setting of TFT use, initial caries
      levels and intensity of TFT application, but was not influenced by exposure to
      water fluoridation or other fluoride sources. D(M)FS PF was on average 14% (95%
      CI, 5% to 23%; p = 0.002) higher in non-placebo controlled trials, 14% (95% CI,
      2% to 26%; p = 0.25) higher in fluoride varnish trials compared with all others,
      and 10% (95% CI, -17% to -3%; p = 0.003) lower in trials of unsupervised home use
      compared with self applied supervised and operator-applied. There was a 0.7%
      increase in the PF per unit increase in baseline caries (95% CI, 0.2% to 1.2%; p
      = 0.004). REVIEWER'S CONCLUSIONS: The benefits of topical fluorides have been
      firmly established on a sizeable body of evidence from randomized controlled
      trials. While the formal examination of sources of heterogeneity between studies
      has been important in the overall conclusions reached, these should be
      interpreted with caution. We were unable to reach definite conclusions about any
      adverse effects that might result from the use of topical fluorides, because data
      reported in the trials are scarce.

PMID- 14583955
TI  - Heliox for nonintubated acute asthma patients.
AB  - BACKGROUND: Helium and oxygen mixtures (heliox), have been used sporadically in
      respiratory medicine for decades. Their use in acute respiratory emergencies such
      as asthma has been the subject of considerable debate. Despite the lapse of more
      than 60 years since it was first proposed, the role of heliox in treating
      patients with acute severe asthma remains unclear. OBJECTIVES: To determine the
      effect of the addition of heliox to standard medical care on the course of acute
      asthma, as measured by pulmonary function testing and clinical endpoints. SEARCH
      STRATEGY: Randomised controlled trials were identified from the Cochrane Airways
      Review Group Asthma Register which is a compilation of systematic searches of
      CINAHL, EMBASE, MEDLINE, and CENTRAL and hand searching of the 20 most productive
      respiratory care journals. In addition, primary authors and experts were
      contacted to identify eligible studies. References from included studies, known
      reviews and texts were also searched. SELECTION CRITERIA: Studies were selected
      for inclusion in the review if they met the following inclusion criteria: 1)
      randomised, single or double blind, controlled trials; 2) children or adults with
      a clinical diagnosis of acute asthma seen in emergency departments or equivalent
      acute care settings; and 3) compared treatment with inhaled heliox to placebo
      (oxygen or air). Two reviewers independently assessed the studies for inclusion
      and quality assessment; disagreement was resolved by a third reviewer and
      consensus. DATA COLLECTION AND ANALYSIS: Data from all included trials were
      combined using the Review Manager (Version 4.1) using random effects weighted
      mean (WMD) and standardised mean differences (SMD), with 95% confidence intervals
      (95% CI). Homogeneity of effect sizes were tested with the Dersimonian and Laird
      method with p<0.1 as the cut point for significance. Sensitivity analyses were
      performed on age (adults vs. children), different helium-oxygen mixtures (80/20,
      vs. 70/30 or 60/40), methodological quality (Jadad score >2 vs. <3) and method of
      heliox use (studies designed to washout air in the lungs and replace it with
      heliox versus studies that used heliox to deliver nebulized therapy). MAIN
      RESULTS: This review has been updated in 2002 to include two new trials. A total
      of six randomised controlled trials were selected for inclusion with a total of
      369 acute asthma patients. Five studies involved adults and one study dealt
      solely with children. Two were assessed as high quality (Jadad score >3). The
      main outcome variable was spirometric measurements (PEF % predicted, PEF L/min,
      FEV1 % of predicted, FEV1L). Heliox use did not improve pulmonary functions
      compared to standard care (SMD = 0.13; 95% CI: -0.09 to 0.34). All pulmonary
      function tests were recorded during heliox administration (15 to 60 min). The
      test of homogeneity was not significant (p=0.25). There were no significant
      differences between groups when adults vs. children, high vs. low quality, and
      high vs. low heliox dose studies were compared. REVIEWER'S CONCLUSIONS: The
      existing evidence does not provide support for the administration of helium
      oxygen mixtures to ED patients with moderate to severe acute asthma. At this
      time, heliox treatment does not have a role to play in the initial treatment of
      patients with acute asthma. Since these conclusions are based upon between-group
      comparisons and small studies, they should be interpreted with caution.
      Additional research in this setting is needed.

PMID- 14583956
TI  - Intravenous immunoglobulins for multiple sclerosis.
AB  - BACKGROUND: From animal experiments, there is evidence to suggest that
      intravenous immunoglobulins can reverse some of the disease process of central
      nervous system demyelination. Subsequently, clinical trials of intravenous
      immunoglobulins have been conducted in people with multiple sclerosis (MS).
      OBJECTIVES: To identify and summarise the evidence that intravenous
      immunoglobulins are safe and beneficial for people with MS. SEARCH STRATEGY: We
      searched the Cochrane Multiple Sclerosis Group trials Register( January 2003) The
      Cochrane Central Register of Controlled Trials (The Cochrane Library issue 4,
      2002), MEDLINE (January 1966 to April 2001), EMBASE (January 1988 to April 2001)
      and reference lists of articles. We also contacted relevant pharmaceutical
      companies and authors of identified trials. SELECTION CRITERIA: Randomised
      controlled trials of intravenous immunoglobulins for the secondary prevention of
      relapses and disease progression in MS. DATA COLLECTION AND ANALYSIS: 913 titles
      and abstracts were obtained from the literature search, and we eventually
      identified 10 clinical trials. All reviewers agreed on the final dataset for
      entry into RevMan 4.1, and summarised the results. Study authors were contacted
      for additional information but no response was obtained. MAIN RESULTS: Of 913
      potential studies, 10 trials were identified with a total of 918 participants,
      four of which are in progress or awaiting publication. The remaining six trials
      were suitable for consideration by this review (344 participants). Only two
      trials met our protocol's inclusion criteria. The four remaining trials were
      excluded as they did not use outcome measures specified in our review (2 trials,
      122 participants), or were of insufficient methodological quality (2 trials, 34
      participants). From the two included trials (168 participants) there was a
      reduction in relapse rate and increased time to first relapse during treatment
      with intravenous immunoglobulins, but reliable disease progression outcomes were
      not reported, nor were magnetic resonance imaging (MRI) data available to support
      clinical information. There may be as many as 574 participants in ongoing or yet
      to be published trials. REVIEWER'S CONCLUSIONS: There is some evidence to support
      use of intravenous immunoglobulins as a preventative treatment for relapses in
      relapsing remitting MS, but further studies should be performed using MRI and
      disease progression endpoints. It may be possible to draw more robust conclusions
      when ongoing or recently completed trials make their data available for review.
      Two rigorously conducted trials with a total of 122 participants did not
      demonstrate a positive clinical benefit, but were excluded from this review as
      they employed outcome measures not specified in our protocol. Immunoglobulins
      were well tolerated with a less than 5% risk of adverse events in participants in
      included trials.

PMID- 14583957
TI  - Antibiotic therapy for prophylaxis against infection of pancreatic necrosis in
      acute pancreatitis.
AB  - BACKGROUND: Acute pancreatitis is a common acute abdominal emergency which lacks
      specific therapy. In severe attacks, areas of the pancreas may become necrotic.
      The mortality risk rises to >40% if sterile necrosis becomes superinfected,
      usually with gut derived aerobic organisms. Experimental and clinical studies
      indicate a window of opportunity of 1-2 weeks, when superinfection, and thus high
      risk surgical debridement, may be prevented by administering systemic antibiotics
      to 'sterilise' tissues adjacent to necrotic areas. There are theoretical risks of
      encouraging antibacterial resistance and opportunistic fungal infections.
      OBJECTIVES: To determine the effectiveness and safety of prophylactic antibiotic
      therapy in patients with severe acute pancreatitis who have developed pancreatic
      necrosis. SEARCH STRATEGY: MEDLINE, EMBASE, and the Cochrane Library were
      searched. We also examined other sources including Conference Abstracts
      (published and unpublished data). SELECTION CRITERIA: Randomised controlled
      trials (RCT) were sought using the search strategy detailed below. No linguistic
      limitations were applied. RCTs were selected in which antibacterial therapy was
      evaluated in patients with severe acute pancreatitis associated with pancreatic
      necrosis proven by intravenous contrast-enhanced computed tomography (CT). No
      linguistic limitations were applied. Searching was undertaken initially in
      November 2001 and updated in March 2003. DATA COLLECTION AND ANALYSIS: Two
      reviewers extracted data from trial publications independently, concerning rates
      for the primary end-points: with respect to: all cause mortality and rates of
      infection of pancreatic necrosis (proven by microbiological examination of fine
      needle aspirate or operative specimens). In addition, secondary end-points
      included peri-pancreatic sepsis, remote sepsis (respiratory, urinary, central
      venous line sources), operative rates, length of hospital stay, adverse events
      including the incidence of drug resistant microorganisms and opportunistic fungal
      infection. MAIN RESULTS: It was possible to evaluate mortality in all four
      included studies, and it demonstrated a survival advantage for antibiotic therapy
      (Odds ratio 0.32, p=0.02). Pancreatic sepsis (infected necrosis) was also
      measurable in all four studies and showed an advantage for therapy (Odds ratio
      0.51, p=0.04). Extra-pancreatic infection could be evaluated in three studies,
      but showed no significant advantage for therapy (Odds ratio 0.47,
      p=0.05).Operative treatment data was available in three studies, but surgery
      rates were not significantly reduced (Odds ratio 0.55, p=0.08). Fungal infections
      showed no strongly increased preponderance with therapy (Odds ratio 0.83, p=0.7),
      but there were no data on infection with resistant organisms. Length of hospital
      stay could only be evaluated in two studies and was not significantly different.
      Sub-group analyses planned for the influence on outcome measures of the
      antibiotic regimen, the time of commencement of therapy in relation to symptom
      onset and/or hospitalisation, duration of therapy, and aetiology could not be
      performed as no data were available. REVIEWER'S CONCLUSIONS: Despite variations
      in drug agent, case mix, duration of treatment and methodological quality
      (especially the lack of double blinded studies), there was strong evidence that
      intravenous antibiotic prophylactic therapy for 10 to 14 days decreased the risk
      of superinfection of necrotic tissue and mortality in patients with severe acute
      pancreatitis with proven pancreatic necrosis at CT. Further studies are required
      to confirm all of the benefits suggested (in particular the need for operative
      debridement), to provide more adequate data on adverse effects, to address the
      choice of antibacterial agents and effects of varying duration of therapy, and
      whether outcome is related to aetiology.

PMID- 14583958
TI  - Smoking cessation for the secondary prevention of coronary heart disease.
AB  - BACKGROUND: Although the importance of smoking as a risk factor for coronary
      heart disease is beyond doubt, the speed and magnitude of risk reduction when a
      smoker with coronary heart disease quits are still subjects of debate.
      OBJECTIVES: To estimate the magnitude of risk reduction when a patient with CHD
      stops smoking. SEARCH STRATEGY: We searched the Cochrane Register of Controlled
      Trials (CENTRAL), MEDLINE, EMBASE, Science Citation Index, CINAHL, PsychLit,
      Dissertation Abstracts, BIDS ISI Index to Scientific and Technical Proceedings,
      UK National Research Register from the start of each database. Sixty-one large
      international cohort studies of cardiovascular disease were identified, and
      contact made with authors to search for any unpublished results. The search was
      supplemented by cross-checking references and contact with various experts. Date
      of last search was April 2003. SELECTION CRITERIA: Any prospective cohort studies
      of patients with a diagnosis of CHD, which include all-cause mortality as an
      outcome measure. Smoking status must be measured on at least two occasions to
      ascertain which smokers have quit, and followed-up for at least two years. DATA
      COLLECTION AND ANALYSIS: Eligibility and trial quality were assessed
      independently by two reviewers. MAIN RESULTS: Twenty studies were included. There
      was a 36% reduction in crude relative risk (RR) of mortality for those who quit
      smoking compared with those who continued to smoke (RR 0.64, 95% confidence
      interval 0.58 to 0.71). There was also a reduction in non-fatal myocardial
      infarctions (crude RR 0.68, 95% confidence interval 0.57 to 0.82). Many studies
      did not adequately address quality issues, such as control of confounding, and
      misclassification of smoking status. However, there was little difference in the
      results for the six 'higher quality' studies, and little heterogeneity between
      these studies. This review was not able to assess how quickly the risk of
      mortality was reduced. REVIEWER'S CONCLUSIONS: Quitting smoking is associated
      with a substantial reduction in risk of all-cause mortality among patients with
      CHD. The pooled crude RR was 0.64 (95% CI 0.58 to 0.71). This 36% risk reduction
      appears substantial compared with other secondary preventive therapies such as
      cholesterol lowering which have received greater attention in recent years. The
      risk reduction associated with quitting smoking seems consistent regardless of
      differences between the studies in terms of index cardiac events, age, sex,
      country, and time period. However, relatively few studies have included large
      numbers of older people, women, or people of non-European descent, and most were
      carried out in Western countries.

PMID- 14583959
TI  - Treatment of hypertension in peripheral arterial disease.
AB  - BACKGROUND: Peripheral arterial disease (PAD) causes considerable morbidity and
      mortality. Hypertension is a risk factor for PAD. Therefore, treatment for
      hypertension must be compatible with the symptoms of PAD. Controversy regarding
      the effects of beta blockade for hypertension in patients with PAD has led many
      physicians to stop prescribing beta-blockers. Little is known about the effects
      of other classes of anti-hypertensive drugs in the presence of PAD. OBJECTIVES:
      To determine the effects of anti-hypertensive drugs on the: cardiovascular events
      and death in patients with hypertension and PAD; symptoms of claudication and
      critical leg ischaemia; progression of PAD, and revascularisation, or
      amputations. SEARCH STRATEGY: Trials were sought via the Specialised Register of
      the Cochrane Peripheral Vascular Diseases Group (last searched July 2003), the
      Cochrane Central Register of Controlled Trials (CENTRAL) (last searched Issue 2,
      2003), and the NHS Database of Abstracts of Reviews of Effectiveness (DARE) (last
      searched August 2002). There were no language restrictions. Abstracts of
      cardiology meetings were studied. Reference lists of papers were also examined.
      SELECTION CRITERIA: Randomised controlled trials of at least one anti
      hypertensive treatment against placebo, or two anti-hypertensive medications
      against each other, with interventions lasting at least one month. Trials had to
      include patients with symptomatic PAD. Trials of poor quality and execution were
      excluded, as were cross-over trials. DATA COLLECTION AND ANALYSIS: Data were
      extracted by one reviewer and checked by the other. Eligible studies were
      excluded when presentation prevented adequate extraction of data, and enquiries
      to authors did not yield the raw data. MAIN RESULTS: Two studies were included in
      the review. In one trial using perindopril in small numbers of patients with PAD,
      there was a marginal increase in claudication distance (weighted mean difference
      (WMD) 8.0, 95% confidence interval (CI) -30.66 to 46.66), but no change in ankle
      brachial pressure index (ABPI), (WMD 0, 95% CI -0.14 to 0.14), and a reduction in
      walking distance (WMD -46, 95 % CI -169.24 to 77.24). In patients undergoing
      angioplasty, a second trial suggested that the calcium antagonist verapamil
      reduced restenosis, although this was not reflected in the maintenance of a high
      ABPI. REVIEWER'S CONCLUSIONS: The evidence for various anti-hypertensive drug
      classes in PAD is poor, so that it is unknown whether significant benefit or risk
      accrues from their use. In view of this, no definite recommendations on use or
      avoidance can be made from the available data.

PMID- 14583960
TI  - Vaginal prostaglandin (PGE2 and PGF2a) for induction of labour at term.
AB  - BACKGROUND: Prostaglandins have been used for induction of labour since the
      1960s. Initial work focused on prostaglandin F2a as prostaglandin E2 was
      considered unsuitable for a number of reasons. With the development of
      alternative routes of administration, comparisons were made between various
      formulations of vaginal prostaglandins. This is one of a series of reviews of
      methods of cervical ripening and labour induction using standardised methodology.
      OBJECTIVES: To determine the effects of vaginal prostaglandins E2 and F2a for
      third trimester cervical ripening or induction of labour in comparison with
      placebo/no treatment or other vaginal prostaglandins (except misoprostol). SEARCH
      STRATEGY: The Cochrane Pregnancy and Childbirth Group trials register (May 2003)
      and bibliographies of relevant papers. SELECTION CRITERIA: Clinical trials
      comparing vaginal prostaglandins used for third trimester cervical ripening or
      labour induction with placebo/no treatment or other methods listed above it on a
      predefined list of labour induction methods. DATA COLLECTION AND ANALYSIS: A
      strategy was developed to deal with the large volume and complexity of trial data
      relating to labour induction. This involved a two-stage method of data
      extraction. MAIN RESULTS: In total, 101 studies were considered: 43 excluded and
      57 (10,039 women) included. One study is awaiting assessment. Vaginal
      prostaglandin E2 compared with placebo or no treatment reduced the likelihood of
      vaginal delivery not being achieved within 24 hours (18% versus 99%, relative
      risk (RR) 0.19, 95% confidence interval (CI) 0.14 to 0.25, 2 trials, 384 women),
      there was no evidence of a difference between caesarean section rates although
      the risk of uterine hyperstimulation with fetal heart rate changes was increased
      (4.6% versus 0.51%, RR 4.14, 95% CI 1.93 to 8.90, 13 trials, 1203 women).
      Comparison of vaginal prostaglandin F2a with placebo showed similar caesarean
      section rates but the cervical score was more likely to be improved (15% versus
      60%, RR 0.25, 95% CI 0.13 to 0.49, 5 trials, 467 women), and the risk of oxytocin
      augmentation reduced (53.9% versus 89.1%, RR 0.60, 95% CI 0.43 to 0.84, 11
      trials, 1265 women) with the use of vaginal PGF2a. There were insufficient data
      to make meaningful conclusions for the comparison of vaginal PGE2 and PGF2a.PGE2
      tablet, gel and pessary appear to be as efficacious as each other. Lower dose
      regimens, as defined in the review, appear as efficacious as higher dose
      regimens. REVIEWER'S CONCLUSIONS: The primary aim of this review was to examine
      the efficacy of vaginal prostaglandin E2 and F2a. This is reflected by an
      increase in successful vaginal delivery rates in 24 hours, no increase in
      operative delivery rates and significant improvements in cervical favourability
      within 24 to 48 hours. Further research is needed to quantify the cost-analysis
      of induction of labour with vaginal prostaglandins, with special attention to
      different methods of administration.

PMID- 14583961
TI  - Nutritional interventions for preventing and treating pressure ulcers.
AB  - BACKGROUND: Pressure ulcers affect 10% of people in hospitals and older people
      are at highest risk. The correlation between nutritional intake and the
      development of pressure ulcers is suggested by several studies, but the results
      are inconsistent. OBJECTIVES: To evaluate the effectiveness of enteral and
      parenteral nutrition on the prevention and treatment of pressure ulcers. SEARCH
      STRATEGY: The Cochrane Wounds Group Specialised Trials Register and the Cochrane
      Central register of Controlled Trials were searched in September 2002. An
      additional search of PubMed and Cinahl and hand search of conference proceedings
      and journals was performed, bibliographies of relevant articles were examined and
      experts in the field as well as manufacturers were contacted in order to find
      additional literature that may be relevant. SELECTION CRITERIA: Randomised
      controlled trials evaluating the effectiveness of enteral or parenteral nutrition
      on the prevention and treatment of pressure ulcers by measuring the incidence of
      new ulcers, ulcer healing or changes in pressure ulcer severity. There were no
      restrictions on patients, setting, date, publication status or language. DATA
      COLLECTION AND ANALYSIS: Abstracts were independently inspected and full articles
      were obtained of potentially relevant studies. In case of disagreement advice was
      sought from a third person (AK). Data extraction and assessment of quality were
      undertaken by the three reviewers independently. MAIN RESULTS: Only 8 randomised
      controlled trials out of 16 potentially relevant articles were included. However,
      most of the 8 trials included are small and of poor methodological quality.
      PREVENTION: Four studies compared a combination of nutritional supplements,
      consisting of a minimum of energy and protein in different dosages, for the
      prevention of pressure ulcers. The largest study found that nutritional
      supplements reduced the number of new pressure ulcers (Bourdel-M 2000). The three
      smaller studies lacked power. TREATMENT: Four studies evaluated the effects of
      nutritional supplements for the treatment of existing pressure ulcers: one trial
      examined mixed nutritional supplements, one trial examined zinc, another the
      effect of proteins, and two studies compared ascorbic acid. The trials included
      are heterogeneous with regard to participants, interventions and outcomes;
      therefore it was considered inappropriate to perform a meta-analysis. REVIEWER'S
      CONCLUSIONS: It was not possible to draw any firm conclusions on the effect of
      enteral and parenteral nutrition on the prevention and treatment of pressure
      ulcers. Further trials of high methodological quality are necessary.

PMID- 14583962
TI  - Symptomatic treatment of the cough in whooping cough.
AB  - BACKGROUND: Whooping cough is an important cause of childhood morbidity and
      mortality. There are 20 to 40 million cases of whooping cough annually world
      wide, 90% of which occur in developing countries, resulting in an estimated 200
      to 300 000 fatalities each year. Much of the morbidity is due to the effects of
      the paroxysmal cough. Corticosteroids, salbutamol (beta 2 - adrenergic
      stimulant), and pertussis-specific immunoglobulin have been proposed as standard
      treatment for the cough. Antihistamines have also been administered. No
      systematic review of the effectiveness of any of these interventions or others
      has been performed. OBJECTIVES: To assess the effectiveness and safety of
      interventions used to reduce the severity of the coughing paroxysms in whooping
      cough in children and adults. SEARCH STRATEGY: We searched the Cochrane Central
      Register of Controlled Trials (CENTRAL) (issue 2, 2003); MEDLINE (January 1966 to
      June 2003); EMBASE (1990 to June 2003) and LILACS (1982 to November 2001). We
      also scanned reference lists of identified trials and contacted authors of
      identified trials and relevant pharmaceutical companies. SELECTION CRITERIA:
      Randomised and quasi-randomised controlled trials of any intervention aimed at
      suppressing the cough in whooping cough; excluding antibiotics and vaccines. DATA
      COLLECTION AND ANALYSIS: Two reviewers independently selected studies and
      extracted data. Our primary outcome was frequency of paroxysms of coughing.
      Secondary outcomes were frequency of vomiting, frequency of whoop, frequency of
      cyanosis, development of serious complications, mortality from any cause, side
      effects due to medication, admission to hospital and duration of hospital stay.
      Disagreements were resolved by discussion. MAIN RESULTS: Nine studies satisfied
      the inclusion criteria but four had insufficient data for meta - analysis of pre
      specified outcomes. Studies were small and poorly reported. The largest study had
      a sample size of 49 and the smallest study 18. All studies were performed in
      industrialised settings. Eligible studies assessed diphenhyramine, pertussis
      immunoglobulin, dexamethasone and salbutamol. No statistically significant
      benefit was found for any of the interventions. Diphenhydramine did not change
      coughing spells (mean increase of coughing spells per 24 hours 1.9 with 95%CI -
      4.7 to 8.5) and pertussis immunoglobulin no change in hospital stay (0.7 days 95%
      CI -3.8 to 2.4), and a mean reduction of 3.1 whoops per 24 hours [95% CI -6.2;
      0.02]. Dexamethasone did not show a clear decrease in hospital stay (-3.5 days
      95% CI - 15.3 to 8.4) and salbutamol showed no change in coughing paroxysms per
      24 hours [-0.22 95% CI - 4.13 to 3.69]. REVIEWER'S CONCLUSIONS: Insufficient
      evidence exists to draw conclusions about the effects of any intervention for the
      cough in whooping cough.

PMID- 14583963
TI  - Cognitive rehabilitation and cognitive training for early-stage Alzheimer's
      disease and vascular dementia.
AB  - BACKGROUND: Memory problems are a defining feature of the early stages of
      Alzheimer's disease (AD) and vascular dementia. Cognitive training and cognitive
      rehabilitation are specific approaches designed to address everyday memory
      difficulties. OBJECTIVES: The main aim was to evaluate the effectiveness and
      impact of cognitive training and cognitive rehabilitation interventions aimed at
      improving memory functioning for people in the early stages of Alzheimer's
      disease or vascular dementia. The two types of intervention were considered
      separately. SEARCH STRATEGY: The CDCIG Specialized Register, which contains
      records from MEDLINE, EMBASE, CINAHL, PsycINFO and many other databases, was
      searched on 9 April 2003. SELECTION CRITERIA: RCTs comparing cognitive
      rehabilitation or cognitive training interventions with comparison conditions,
      and reporting outcomes for the person with dementia and/or the family caregiver,
      were considered for inclusion. DATA COLLECTION AND ANALYSIS: Six studies
      reporting cognitive training interventions were included. Statistical analyses
      were conducted to provide an indication of intervention effect sizes. Data from
      ordinal scales was treated as continuous, and a fixed effects model was applied
      in calculating weighted mean differences and 95% confidence intervals. No studies
      were found that reported a fully individualised cognitive rehabilitation
      approach. MAIN RESULTS: None of the six studies reporting cognitive training
      interventions demonstrated any statistically significant effects in any domain,
      although there were indications of some modest, non-significant effects in
      various domains of cognitive functioning. REVIEWER'S CONCLUSIONS: The present
      findings do not provide strong support for the use of cognitive training
      interventions for people with early-stage AD or vascular dementia, although these
      findings must be viewed with caution due to the limited number of RCTs available
      and to the methodological limitations identified, and further well-designed
      trials would help to provide more definitive evidence. Due to a complete absence
      of RCTs evaluating an individualised cognitive rehabilitation approach, It is not
      possible at present to draw conclusions about the efficacy of individualised
      cognitive rehabilitation interventions for people with early-stage dementia, and
      further research is required in this area.

PMID- 14583964
TI  - Colchicine as an oral corticosteroid sparing agent for asthma.
AB  - BACKGROUND: Oral corticosteroids are used as a treatment for asthma, but they are
      often associated with serious side effects. Colchicine is an anti-inflammatory,
      immuno modulating agent, which could potentially have a beneficial effect in the
      treatment of asthma as well as act as a steroid-sparing agent. OBJECTIVES: To
      determine the effectiveness of colchicine as an oral corticosteroid sparing agent
      for in the treatment of chronic asthma. SEARCH STRATEGY: We searched the Cochrane
      Airways Group trials register (November 2002), SIGLE (1980 to 2001) and reference
      lists of potential articles. We also contacted researchers in the field.
      SELECTION CRITERIA: Randomised controlled trials investigating the addition of
      colchicine compared to placebo in stable steroid dependent asthmatics. DATA
      COLLECTION AND ANALYSIS: No trials were found that met the inclusion criteria.
      MAIN RESULTS: We were unable to perform any meta-analyses. Two small studies have
      assessed the efficacy of colchicine subsequent to inhaled steroid withdrawal and
      as a tapering agent in inhaled steroids. Both studies failed to detect a
      significant difference between colchicine and placebo. REVIEWER'S CONCLUSIONS: No
      relevant trials have been published, so there is no evidence to indicate that
      colchicine is beneficial or otherwise in the management of steroid-dependent
      asthmatic patients. There is a need for well designed randomised controlled
      trials to be performed.

PMID- 14583965
TI  - Chloroquine as a steroid sparing agent for asthma.
AB  - BACKGROUND: For the majority of chronic asthmatics, symptoms are best controlled
      using inhaled steroids, but for a small group of asthma sufferers, symptoms
      cannot be controlled using inhaled steroids and instead continuous use of high
      dosage oral steroids (corticosteroids) are required. However, using high dosage
      oral steroids for long periods is associated with severe side effects. Steroid
      sparing treatments have been sought and one of these is chloroquine. Chloroquine
      is an anti-inflammatory agent, also used in the treatment of malarial infection
      and as a second-line therapy in the treatment of rheumatoid arthritis,
      sarcoidosis and systemic lupus erythematosus. All these diseases are associated
      with immunologic abnormalities hence the speculation that chloroquine might be
      used to control severe, poorly controlled bronchial asthma. There is a need to
      systematically evaluate the evidence regarding its use to reduce or eliminate
      oral corticosteroid use in asthma. OBJECTIVES: The object of this review was to
      assess the efficacy of adding chloroquine to oral corticosteroids in patients
      with chronic asthma who are dependent on oral corticosteroids with the intention
      of minimising or eventually eliminating the use of these oral steroids. SEARCH
      STRATEGY: Searches of the Cochrane Airways Group asthma and wheeze trials
      register were undertaken with predefined search terms in February 2003. SELECTION
      CRITERIA: Only studies with a randomised placebo-controlled design met the
      inclusion criteria for the review. DATA COLLECTION AND ANALYSIS: Two reviewers
      independently assessed studies for suitable in the review. Data were extracted
      and entered into RevMan 4.2.2 MAIN RESULTS: One small study was included in the
      review. No significant findings were reported. REVIEWER'S CONCLUSIONS: There is
      insufficient evidence to support the use of chloroquine as an oral steroid
      sparing agent in chronic asthma. Further trials should optimise oral steroid
      dosage before addition of the steroid-sparing agent.

PMID- 14583966
TI  - Cooling for newborns with hypoxic ischaemic encephalopathy.
AB  - BACKGROUND: Newborn animal and human pilot studies suggest that mild hypothermia
      following peripartum hypoxia-ischaemia in newborn infants may reduce neurological
      sequelae, without adverse effects. OBJECTIVES: To determine whether therapeutic
      hypothermia in encephalopathic asphyxiated newborn infants reduces mortality and
      long-term neurodevelopmental disability, without clinically important side
      effects. SEARCH STRATEGY: The standard search strategy of the Neonatal Review
      Group as outlined in the Cochrane Library (Issue 2, 2003) was used. Randomised
      controlled trials evaluating therapeutic hypothermia in term newborns with
      hypoxic ischaemic encephalopathy were identified by searching the Oxford Database
      of Perinatal Trials, the Cochrane Central Register of Controlled Trials (CENTRAL,
      The Cochrane Library Issue Issue 2, 2003), MEDLINE (1966 to July 2003), previous
      reviews including cross-references, abstracts, conferences, symposia proceedings,
      expert informants and journal hand searching. SELECTION CRITERIA: Randomised
      controlled trials comparing the use of therapeutic hypothermia with normothermia
      in encephalopathic newborn infants with evidence of peripartum asphyxia and
      without recognisable major congenital anomalies were included. The primary
      outcome measure was death or long-term major neurodevelopmental disability. Other
      outcomes included adverse effects of cooling and 'early' indicators of
      neurodevelopmental outcome. DATA COLLECTION AND ANALYSIS: Three reviewers
      independently selected, assessed the quality of and extracted data from the
      included studies. Authors were contacted for further information. Meta-analyses
      were performed using relative risk and risk difference for dichotomous data, and
      weighted mean difference for continuous data with 95% confidence intervals. MAIN
      RESULTS: Two randomised controlled trials were included in this review,
      comprising 50 term infants with moderate/ severe encephalopathy and evidence of
      intrapartum asphyxia. There was no significant effect of therapeutic hypothermia
      on the combined outcome of death or major neurodevelopmental disability in
      survivors followed. No adverse effects of hypothermia on short term medical
      outcomes or on some 'early' indicators of neurodevelopmental outcome were
      detected. REVIEWER'S CONCLUSIONS: Although two small randomised controlled trials
      demonstrated neither evidence of benefit or harm, current evidence is inadequate
      to assess either safety or efficacy of therapeutic hypothermia in newborn infants
      with hypoxic ischaemic encephalopathy. Therapeutic hypothermia for
      encephalopathic asphyxiated newborn infants should be further evaluated in well
      designed randomised controlled trials.

PMID- 14583967
TI  - Selenium supplementation to prevent short-term morbidity in preterm neonates.
AB  - BACKGROUND: Selenium is an essential trace element and component of a number of
      selenoproteins including glutathione peroxidase, which has a role in protecting
      against oxidative damage. Selenium is also known to play a role in
      immunocompetence. Blood selenium concentrations in newborns are lower than those
      of their mothers and lower still in preterm infants. In experimental animals low
      selenium concentrations appear to increase susceptibility to oxidative lung
      disease. In very preterm infants low selenium concentrations have been associated
      with an increased risk of chronic neonatal lung disease and retinopathy of
      prematurity. OBJECTIVES: To assess the benefits and harms of selenium
      supplementation in preterm or very low birthweight infants. SEARCH STRATEGY:
      Searches were made of the Cochrane Central Register of Controlled Trials
      (CENTRAL, The Cochrane Library, Issue 2, 2003), MEDLINE (1966-May 2003), and
      Embase (1980-May 2003). The reference lists of recent trials were also searched
      and abstracts from the Society for Pediatric Research from 1990 were hand
      searched. SELECTION CRITERIA: Randomised controlled trials which compared
      selenium supplementation either parenterally or enterally with placebo or nothing
      from soon after birth in preterm or very low birthweight infants and which
      reported clinical outcomes were considered for the review. DATA COLLECTION AND
      ANALYSIS: Data on selenium supplementation dose, formulation and route of
      administration; mortality, oxygen requirement at 28 days and 36 weeks post
      menstrual age, retinopathy of prematurity, and one or more episodes of sepsis;
      blood selenium and glutathione peroxidase concentrations at or close to 28 days,
      were excerpted by both reviewers independently. Data analysis was conducted
      according to the standards of the Cochrane Neonatal Review Group. MAIN RESULTS:
      Three eligible trials were identified. Two trials, including one trial with a
      much larger sample size than the others combined, were from geographical areas
      with low population selenium concentrations. Meta-analysis of the pooled data
      showed a significant reduction in the proportion of infants having one or more
      episodes of sepsis associated with selenium supplementation [summary RR 0.73
      (0.57, 0.93); RD -0.10 (-0.17, -0.02); NNT 10 (5.9, 50)]. Supplementation with
      selenium was not associated with improved survival, a reduction in neonatal
      chronic lung disease or retinopathy of prematurity. REVIEWER'S CONCLUSIONS:
      Supplementing very preterm infants with selenium is associated with benefit in
      terms of a reduction in one or more episodes of sepsis. Supplementation was not
      associated with improved survival, a reduction in neonatal chronic lung disease
      or retinopathy of prematurity. Supplemental doses of selenium for infants on
      parenteral nutrition higher than those currently recommended may be beneficial.
      The data are dominated by one large trial from a country with low selenium
      concentrations and may not be readily translated to other populations.

PMID- 14583968
TI  - Percutaneous transluminal rotational atherectomy for coronary artery disease.
AB  - BACKGROUND: Percutaneous transluminal coronary rotational atherectomy (PTCRA)
      debulks atherosclerotic plaque from coronary arteries using an abrasive burr. On
      rotation, the burr selectively removes hard tissue. OBJECTIVES: To assess the
      effects of PTCRA for coronary artery disease in patients with non-complex and
      complex lesions (e.g., ostial, long, or diffuse lesions or those arising from in
      stent restenosis) of the coronary arteries. SEARCH STRATEGY: We searched the
      Heart Group specialised register, the Cochrane Library to Issue 2, 2001, and
      MEDLINE, CINAHL, EMBASE and Current Contents to December 2002 and reviewed
      reference lists for relevant articles. SELECTION CRITERIA: We included randomised
      and quasi-randomised controlled trials of PTCRA compared with placebo, no
      treatment or another intervention and excluded cross-over trials. DATA COLLECTION
      AND ANALYSIS: Data were extracted independently by two authors. We asked authors
      of trials to provide information when missing data was encountered. Statistical
      summaries used risk ratios (RR) and weighted mean differences. MAIN RESULTS: We
      included 9 trials enrolling 3,066 patients. There was no evidence of the
      effectiveness of PTCRA in non-complex lesions. In complex lesions, there were no
      statistically significant differences in restenosis rates at 6 months (relative
      risk 1.00; 95% confidence interval 0.83 to 1.20) and 1 year (relative risk 1.21;
      95% confidence interval =0.95 to 1.55) in those receiving PTCRA with adjunctive
      PTCA (PTCRA/PTCA) compared to those receiving PTCA alone. Morphological
      characteristics distinguishing complex lesions have not been examined in parallel
      arm randomised controlled trials. There is equivocal evidence of the
      effectiveness of PTCRA in in-stent restenosis. Compared to angioplasty alone,
      PTCRA/PTCA did not result in a statistically significant increase in the risk of
      major adverse cardiac events (myocardial infarction, emergency cardiac surgery or
      death) during the in-hospital period (relative risk 1.19; 95% confidence interval
      =0.78 to 1.83). Compared to angioplasty, PTCRA was associated with 9 times the
      risk of an angiographically-detectable vascular spasm (relative risk 9.23; 95%
      confidence interval 4.61 to 18.47), 4 times the risk of perforation (relative
      risk 3.87; 95% confidence interval 0.82 to 18.21) and about 2 times the risk of
      transient vessel occlusions (relative risk 2.28; 95% confidence interval 1.00,
      5.19) while angiographic dissections (relative risk 0.49; 95% confidence interval
      0.33 to 0.75) and stents used as a bailout procedure (relative risk 0.38; 95%
      confidence interval 0.22 to 0.65) were less common. REVIEWER'S CONCLUSIONS: When
      conventional PTCA is feasible, PTCRA appears to confer no additional benefits.
      There is limited published evidence and no long-term data to support the routine
      use of PTCRA in in-stent restenosis. In certain circumstances (e.g., patients
      ineligible for cardiac surgery, those with architecturally complex lesions, or
      those with lesions that fail PTCA), PTCRA may achieve satisfactory
      revascularisation in subsequent procedures.

PMID- 14583969
TI  - Antimicrobial drugs for treating methicillin-resistant Staphylococcus aureus
      colonization.
AB  - BACKGROUND: Eradication strategies for methicillin-resistant Staphylococcus
      aureus (MRSA) are variable. We sought to summarize the evidence for use of
      antimicrobial agents to eradicate MRSA. OBJECTIVES: To describe the effects of
      topical and systemic antimicrobial agents on nasal and extra-nasal MRSA carriage,
      adverse events, and incidence of subsequent MRSA infections. SEARCH STRATEGY: We
      searched the Cochrane Infectious Diseases Group's trials register (August 2003),
      the Cochrane Central Register of Controlled Trials (Issue 3, 2003), MEDLINE (1966
      to 2003), EMBASE (1988 to 2003), handsearched relevant literature, and contacted
      MRSA experts and the manufacturer of mupirocin. SELECTION CRITERIA: Randomized
      controlled trials of patients colonized with MRSA comparing topical or systemic
      antimicrobials to placebo or no treatment, and trials comparing various
      combinations of topical or systemic agents to no treatment, placebo, or to
      topical or systemic agents. DATA COLLECTION AND ANALYSIS: Two reviewers
      independently applied inclusion criteria to potentially relevant trials, assessed
      trial methodological quality, and extracted data. Primary outcomes included
      eradication of MRSA, infection due to MRSA, and adverse events. MAIN RESULTS: Six
      trials (384 participants) met the inclusion criteria. No difference in MRSA
      eradication was detected in four studies: one that compared mupirocin to placebo,
      two that compared one systemic agent to no treatment (fusidic acid in one and
      rifampin or minocycline in the other) and one that compared mupirocin to topical
      fusidic acid and oral trimethoprim-sulfamethoxazole, examining nasal MRSA
      eradication as an outcome. One study compared minocycline to rifampin, with
      rifampicin being more effective in relation to eradication of MRSA from all sites
      at day 30 (relative risk 0.16; 95% confidence intervals 0.02 to 1.00), but the
      difference at 90 days was not statistically significant (n = 18). Two studies
      (one testing novobiocin and rifampin, the other ciprofloxacin and rifampin,
      versus trimethoprim-sulfamethoxazole and rifampin) did not demonstrate a
      difference in eradication of MRSA at all sites (n = 94). Adverse events with
      systemic agents occurred in up to 20% of participants, however reporting was
      sporadic and denominators small. All trials reported development of resistance to
      antimicrobial agents used. REVIEWER'S CONCLUSIONS: There is insufficient evidence
      to support use of topical or systemic antimicrobial therapy for eradicating nasal
      or extra-nasal MRSA. There is no demonstrated superiority of either topical or
      systemic therapy, or of combinations of these agents. Potentially serious adverse
      events and development of antimicrobial resistance can result from therapy.

PMID- 14583970
TI  - Radioisotopes for metastatic bone pain.
AB  - BACKGROUND: Bone metastases manifest through pain, which can arise even before
      the injury is radiologically detected. Pain occurs as a result of bone
      destruction and, as more destruction ensues, more pain can be experienced.
      Radiculopathies, plexopathies and shrinkage of spinal nerves due to tumour growth
      and fractures are very frequent in these patients. Relief of pain from bone
      metastasis can be achieved by treating the cancer itself; radiotherapy;
      conventional analgesics; and specific drugs that work on the bone tumour-induced
      alteration: biphosphonates, calcitonin or radioactive agents. OBJECTIVES: To
      determine the efficacy of radioisotopes to control metastatic pain in patients
      with bone metastases and complications due to bone metastases (hypercalcaemia,
      bone fracture and spinal cord compression) as well as its efficacy in terms of
      patient survival and adverse effects. SEARCH STRATEGY: Randomised and controlled
      clinical trials related to this review were retrieved electronically using
      MEDLINE (1966-2003), EMBASE (1974-2003) and Cochrane Central Register of
      Controlled Trials (CENTRAL) (Issue 1 2003). general strategies to identify RCTs
      were combined with specific commands to identify trials of radioisotopes and
      metastatic bone pain. SELECTION CRITERIA: The inclusion criteria were: randomised
      trials of patients with metastatic bone pain that compared treatment with
      radioisotopes and placebo, and where the major outcome was either pain or
      complications of bone metastases (eg, hypercalcaemia, bone fracture, spinal cord
      compression) assessed at least four weeks after treatment. DATA COLLECTION AND
      ANALYSIS: The quality of included studies was assessed using the Jadad scale and
      the Oxford Pain Validity Score. Two independent reviewers extracted the data and
      completed a standard form designed for that purpose. An intention-to-treat
      analysis was performed, and global estimates of effect were calculated using a
      random effects model. MAIN RESULTS: Four trials (325 patients) provided data that
      suggest a small effect of radioisotopes on pain control both at short and medium
      term (one to six months). No evidence was available to assess long-term effects
      (12 months). Only one study provided data on analgesia use and concluded that
      patients given either radioisotopes or placebo showed similar levels of analgesic
      use when compared to baseline use. Leukocytopenia and thrombocytopenia are
      secondary effects associated with the administration of radioisotopes. The
      incidence of leukocytopenia is significantly greater in patients treated with
      radioisotopes (RR=4.56, 95% CI (1.22,17.08)). There were also a greater number of
      thrombocytopenia events in the treatment group, without reaching statistical
      significance. REVIEWER'S CONCLUSIONS: The efficacy of radioisotopes has been
      assessed in clinical trials with small sample sizes and short-term evaluations of
      the outcomes. There is some evidence indicating that radioisotopes may give
      complete reduction in pain over one to six months with no increase in analgesic
      use, but adverse effects, specifically leukocytopenia and thrombocytopenia, have
      also been experienced.

PMID- 14583971
TI  - Antidepressants versus placebo for people with bulimia nervosa.
AB  - BACKGROUND: Bulimia Nervosa (BN) represents an important public health problem
      and is related to serious morbidity and even mortality. This review attempted to
      systematically evaluate the use of antidepressant medications compared with
      placebo for the treatment of bulimia nervosa. OBJECTIVES: The primary objective
      of this review was to determine whether using antidepressant medications was
      clinically effective for the treatment of bulimia nervosa. The secondary
      objectives were:(i) to examine whether there was a differential effect for the
      various classes/types of antidepressants with regard to effectiveness and
      tolerability(ii) to test the hypothesis that the effect of antidepressants on
      bulimic symptoms was independent of its effect on depressive symptoms SEARCH
      STRATEGY: (1) electronic searches of MEDLINE (1966 to December 2002), EMBASE
      (1980-December 2002), PsycINFO (to December 2002), LILACS & SCISEARCH (to
      2002)(2) the Cochrane Register of Controlled Trials and the Cochrane Depression,
      Anxiety and Neurosis Group Register - ongoing(3) inspection of the references of
      all identified trials(4) contact with the pharmaceutical companies and the
      principal investigator of included trials(5) inspection of the International
      Journal of Eating Disorders - ongoing SELECTION CRITERIA:  INCLUSION CRITERIA:
      every randomised, placebo-controlled trial in which antidepressant medications
      were compared to placebo to reduce the symptoms of bulimia nervosa in patients of
      any age or gender.Quality criteria: reports were considered adequate if they were
      classified as A or B according to the Cochrane Manual. The Jadad scale, with a
      cut off of 2 points, was applied to check the validity of the above referred
      criterion but was not used as an inclusion criterion. DATA COLLECTION AND
      ANALYSIS: Data were extracted independently by two reviewers for each included
      trial. Dichotomous data were evaluated by the relative risk with 95% confidence
      intervals (CI) around this measure, based on the random effects model; continuous
      data were evaluated by the standardised mean difference with the 95% CI. NNT was
      calculated using the inverse of the absolute risk reduction. MAIN RESULTS:
      Currently the review includes 19 trials comparing antidepressants with placebo: 6
      trials with TCAs (imipramine, desipramine and amitriptyline), 5 with SSRIs
      (fluoxetine), 5 with MAOIs (phenelzine, isocarboxazid, moclobemide and
      brofaromine) and 3 with other classes of drugs (mianserin, trazodone and
      bupropion). Similar results were obtained in terms of efficacy for these
      different groups of drugs. The pooled RR for remission of binge episodes was 0.87
      (95% CI 0.81-0.93; p<0,001) favouring drugs. The NNT for a mean treatment
      duration of 8 weeks, taking the non-remission rate in the placebo controls of 92%
      as a measure of the baseline risk was 9 (95% CI 6 - 16). The RR for clinical
      improvement, defined as a reduction of 50% or more in binge episodes was 0.63
      (95% CI 0.55-0.74) and the NNT for a mean treatment duration of 9 weeks was 4
      (95% CI 3 - 6), with a non-improvement rate of 67% in the placebo group. Patients
      treated with antidepressants were more likely to interrupt prematurely the
      treatment due to adverse events. Patients treated with TCAs dropped out due to
      any cause more frequently that patients treated with placebo. The opposite was
      found for those treated with fluoxetine, suggesting it may be a more acceptable
      treatment. Independence between antidepressant and anti-bulimic effects could not
      be evaluated due to incomplete published data. REVIEWER'S CONCLUSIONS: The use of
      a single antidepressant agent was clinically effective for the treatment of
      bulimia nervosa when compared to placebo, with an overall greater remission rate
      but a higher rate of dropouts. No differential effect regarding efficacy and
      tolerability among the various classes of antidepressants could be demonstrated.

PMID- 14583972
TI  - Homoeopathy for induction of labour.
AB  - BACKGROUND: This is one of series of reviews of cervical ripening and labour
      induction using standardised methodology. Homoeopathy involves the use, in
      dilution, of substances which cause symptoms in their undiluted form. A type of
      herb, 'caulophyllum' is one type of homoeopathic therapy that has been used to
      induce labour. OBJECTIVES: To determine the effects of homoeopathy for third
      trimester cervical ripening or induction of labour. SEARCH STRATEGY: The Cochrane
      Pregnancy and Childbirth Group Trials Register (13 May 2003), and bibliographies
      of relevant papers. SELECTION CRITERIA: Randomised controlled trials comparing
      homeopathy used for third trimester cervical ripening or labour induction with
      placebo/no treatment or other methods listed above it on a predefined list of
      labour induction methods. DATA COLLECTION AND ANALYSIS: A generic strategy was
      developed to deal with the large volume and complexity of trial data relating to
      labour induction. This involved a two-stage method of data extraction. The
      initial data extraction was done centrally. MAIN RESULTS: Two trials involving
      133 women were included in the review. The trials were placebo controlled and
      double blind, but the quality was not high. Insufficient information was
      available on the method of randomisation and the study lacked clinically
      meaningful outcomes. This trials demonstrated no differences in any primary or
      secondary outcome between the treatment and control group. REVIEWER'S
      CONCLUSIONS: There is insufficient evidence to recommend the use of homoeopathy
      as a method of induction. It is likely that the demand for complementary medicine
      will continue and women will continue to consult a homoeopath during their
      pregnancy. Although caulophyllum is a commonly used homoeopathic therapy to
      induce labour, the treatment strategy used in the one trial in which it was
      evaluated may not reflect routine homoeopathy practice. Rigorous evaluations of
      individualised homeopathic therapies for induction of labour are needed.

PMID- 14583973
TI  - Combined spinal-epidural versus epidural analgesia in labour.
AB  - BACKGROUND: Traditional epidural techniques have been associated with prolonged
      labour, use of oxytocin augmentation, and increased incidence of instrumental
      vaginal delivery. The combined spinal-epidural (CSE) technique has been
      introduced in an attempt to reduce these adverse effects. CSE is believed to
      improve maternal mobility during labour and provide more rapid onset of analgesia
      than epidural analgesia. OBJECTIVES: To assess the relative effects of combined
      spinal-epidural versus epidural analgesia during labour. SEARCH STRATEGY: The
      Cochrane Pregnancy and Childbirth Group Trials Register (July 2002), the Cochrane
      Controlled Trials Register (The Cochrane Library, Issue 3, 2002), MEDLINE (1966
      to June 2002) and EMBASE (1974 to June 2002). SELECTION CRITERIA: All published
      randomised controlled trials involving a comparison of CSE with epidural
      analgesia initiated for women in the first stage of labour. DATA COLLECTION AND
      ANALYSIS: Trials identified from searching were assessed for inclusion by the
      same two reviewers independently. Review Manager software was used for
      calculation of the treatment effect represented by odds ratios (OR) and weighted
      mean difference (WMD) using a fixed effects model with 95% confidence intervals
      (CI). MAIN RESULTS: Fourteen trials (2047 women) met our inclusion criteria. Of
      the 25 outcomes analysed from these studies CSE shows a reduced time from first
      injection to effective maternal analgesia WMD -5.50 minutes (95% CI -6.47 to 
      4.52; four trials), an increased incidence of maternal satisfaction OR 4.69 (95%
      CI 1.27 to 17.29; three trials), and an increased incidence of pruritus OR 2.79
      (95% CI 1.87 to 4.18; nine trials). No difference was found between CSE and
      epidural techniques with regards to maternal mobility, rescue analgesia
      requirements, the incidence of post dural puncture headache (PDPH) or blood
      patch, hypotension, urinary retention, mode of delivery, or admission of the baby
      to the neonatal unit. REVIEWER'S CONCLUSIONS: There is no standard CSE or
      epidural technique. Compared with epidural, CSE provides faster onset of
      effective pain relief from the time of injection, and increases the incidence of
      maternal satisfaction. However, CSE women experience more itch. There is no
      difference between CSE and epidural techniques with respect to: the incidence of
      forceps delivery, maternal mobility, PDPH, caesarean section rates or admission
      of babies to the neonatal unit. It is not possible to draw any meaningful
      conclusions regarding rare complications such as nerve injury and meningitis.

PMID- 14583974
TI  - Heroin maintenance for chronic heroin dependents.
AB  - BACKGROUND: Dependent heroin users are characterised by the persistence of use in
      spite of the difficulties they experience with health, law, social achievements
      and personal relationships. The present review will consider maintenance
      treatment in which the patients enter programs of pharmacological administration
      tailored to achieve patient stabilisation. Many medications have been used for
      this purpose such as: Methadone, Buprenorphine and LAAM. The present review will
      focus on maintenance treatment through the prescription of heroin. OBJECTIVES: To
      assess the efficacy and acceptability of heroin maintenance versus methadone or
      other substitution treatments for opioid dependence, in retaining patients in
      treatment; reducing the use of illicit substances and improving health and social
      functioning. SEARCH STRATEGY: The Cochrane Central Register of Trials (CENTRAL)
      issue 4, 2002; MEDLINE (on Silver Platter) 1966-2002; EMBASE (on OVID) 1980-2000
      and CINAHL till 2000 were searched. There was no language or publication year
      restrictions. Many researchers were contacted for information. SELECTION
      CRITERIA: Randomised controlled trials of heroin (alone or combined with
      methadone) maintenance treatment compared with any other pharmacological
      treatments. DATA COLLECTION AND ANALYSIS: The trials were independently assessed
      for inclusion and methodological quality by the reviewers. Data were extracted
      independently and double checked. Studies were not pooled together because of
      heterogeneity. MAIN RESULTS: 2400 references were obtained and 20 studies were
      eligible, 4 met the inclusion criteria for a total of 577 patients. The studies
      included could not be analysed cumulatively because of heterogeneity of
      interventions and outcomes considered. Two studies compared injected heroin to
      oral methadone for 1 year (270 patients) but considered different outcomes; one
      study compared injected heroin and methadone to oral methadone for 6 months (51
      patients); and one compared inhaled heroin and methadone to oral methadone for 1
      year (235 patients). Retention in treatment: in two studies there was no
      statistical difference between groups; one study (N=90) had a RR=2.49 (95% CI
      1.51-4.10) in favour of heroin; one study (N=235) had a RR 0.79 (95%CI 0.68-0.90)
      in favour of methadone. Relapse to illegal heroin use, based on self report: in
      one study the proportion of people still using heroin were 64% in the heroin
      group, 59% methadone group; in the other study the RR was 0.33 (95%CI 0.15-0.72)
      in favour of heroin. The remaining studies did not provide the data. Criminal
      offence: one of the two studies which provided details about this showed the
      potential of heroin prescription in reducing the risk of being charged RR 0.32
      (95% CI 0.14-0.78). Social functioning: the two studies reporting this outcome
      did not show statistical difference between intervention groups. The two most
      recent studies considered criminal offence and social functioning as part of a
      multidomain outcome measure and showed higher improvement among those treated
      with heroin plus methadone over those on methadone only. REVIEWER'S CONCLUSIONS:
      No definitive conclusions about the overall effectiveness of heroin prescription
      is possible because of non-comparability of the experimental studies available to
      be included in this review. Results favouring heroin treatment come from studies
      conducted in countries where the treatment system is comprehensive and easy
      accessible Methadone Maintenance Treatment at effective dosages is available. In
      those studies heroin prescription was addressed to patients who had failed
      previous methadone treatments.

PMID- 14583975
TI  - Antithyroid drug regimen for treating Graves' hyperthyroidism.
AB  - BACKGROUND: Antithyroid drugs are widely used in the therapy of hyperthyroidism.
      There are wide variations in the dose, regimen or duration of treatment used by
      health professionals. OBJECTIVES: To assess the effects of dose, regimen and
      duration of antithyroid drug therapy for Graves' hyperthyroidism. SEARCH
      STRATEGY: We searched the Cochrane Central Register of Controlled Trials
      (Central), MEDLINE, EMBASE, BIOSIS, CINAHL, HEALTHSTAR, Current Controlled Trials
      and reference lists. We contacted investigators and hand searched conference
      abstracts. Most recent search: June 2002. SELECTION CRITERIA: Randomised and
      quasi-randomised trials of antithyroid medication for Graves' hyperthyroidism
      were used. DATA COLLECTION AND ANALYSIS: Trial allocation to included, excluded
      and awaiting assessment categories was made by consensus. Two reviewers
      independently extracted data and assessed trial quality. Pooling of data for
      primary outcomes, and select exploratory analyses were undertaken. MAIN RESULTS:
      Nineteen randomised trials involving 2233 participants were included. Overall the
      quality of trials as reported was poor; specifically in terms of allocation
      concealment, assessor blinding and loss to follow-up. Four trials examined the
      effect of duration of therapy on relapse rates of Graves' hyperthyroidism. In one
      trial using the Titration regimen, longer duration therapy (18 months) had
      significantly fewer relapses (37% vs 58%) than six month therapy (Odds ratio (OR)
      = 0.42, 95% confidence interval (CI) 0.18 to 0.96). In one quasi-randomised trial
      using the Block-Replace regimen, there was no significant difference between the
      six and 12 month (relapses rates 41% versus 35%) arms of the study. Extending the
      duration of therapy to over 18 months was not associated with improved relapse
      rates (Peto OR = 0.75, 95% CI 0.39 to 1.43). Ten trials examined the effect of
      Block-Replace versus Titration regime. Relapse rates were similar in both groups
      at 54% in the Block-Replace group and 58% in the Titration group (Peto OR = 0.83,
      95% CI 0.63 to 1.10). Participants reporting rashes (11% versus 5%) and
      withdrawing due to side effects (16% versus 9%) were significantly higher in the
      Block-Replace group compared to the Titration group respectively. Three studies
      considered the addition of thyroxine after initial therapy with antithyroid
      drugs. There was significant heterogeneity between the studies and the difference
      between the two groups were not significant (Odds ratio = 0.58, 95% CI 0.05 to
      6.21). REVIEWER'S CONCLUSIONS: The evidence (based on three studies) suggests
      that the optimal duration of antithyroid drug therapy for the Titration regimen
      is 12 to 18 months. The six month Block-Replace regimen was found to be as
      effective as the 12 month treatment in one quasi-randomised study. The Titration
      (low dose) regimen had fewer adverse effects than the Block-Replace (high dose)
      regimen and was no less effective in trials (based on 10 trials) of equal
      duration. The incidence of hypothyroidism was not reported and there were no
      deaths in the study populations.

PMID- 14583976
TI  - Non surgical therapy for anal fissure.
AB  - BACKGROUND: Because of the disability associated with surgery for anal fissure
      and the risk of incontinence, medical alternatives for surgery have been sought.
      Most recently, pharmacologic methods that relax the anal smooth muscle, to
      accomplish reversibly what occurs in surgery, have been used to obtain fissure
      healing. OBJECTIVES: To assess the efficacy and morbidity of various medical
      therapies for anal fissure. SEARCH STRATEGY: Search terms include "anal fissure
      randomized". SELECTION CRITERIA: Studies in which participants were randomized to
      a non-surgical therapy for anal fissure. Comparison groups may include an
      operative procedure, an alternate medical therapy or placebo. Chronic fissure,
      acute fissure and fissure in children are included in the review. Atypical
      fissures associated with inflammatory bowel disease or cancer or anal infection
      are excluded. DATA COLLECTION AND ANALYSIS: Data were abstracted from published
      reports and meeting abstracts, assessing method of randomization, blinding,
      "intention to treat" and drop-outs, therapies, supportive measures (applied to
      both groups), dosing and frequency and cross-overs. Dichotomous outcome measures
      included Non-healing of the fissure (a combination of persistence and
      recurrence), and Adverse events (including incontinence, headache, infection,
      anaphylaxis). Continuous outcome measures included measures of pain relief and
      anorectal manometry. MAIN RESULTS: 21 different comparisons of the ability of
      medical therapies to heal anal fissure have been reported in 31 RCTs. Nine agents
      were used (nitroglycerin ointment (GTN), isosorbide dinitrate, Botulinum toxin
      (Botox), diltiazem, nifedipine (Calcium channel blockers or Cachablos),
      hydrocortisone, lignocaine, bran, placebo) as well as anal dilators and surgical
      sphincterotomy. When two studies are excluded from analysis due to quality
      concerns, the significance disappears in the three main analyses: GTN vs. placebo
      group (0.78; 0.56-1.08), in children (0.96; 0.48-1.92) and adults (0.73; 0.50
      1.07). That is, GTN was, in this modified analysis, not significantly better than
      placebo in curing anal fissure. Cachablos were not tested against placebo, but in
      a comparison to GTN, Cachablo was equivalent in its ability to cure fissure (odds
      ratio 0.66; 0.22-2.01). Botox, in a meta-analysis of two studies compared to
      placebo, showed no significant advantage in efficacy (0.75; 0.32-1.77), and in a
      comparison to GTN analyzing two studies, was also not significantly better than
      GTN (0.48; 0.21-1.10). REVIEWER'S CONCLUSIONS: Medical therapy for chronic anal
      fissure, acute fissure and fissure in children may be applied with a chance of
      cure that is only marginally better than placebo, and, for chronic fissure in
      adults, far less effective than surgery.

PMID- 14583977
TI  - Impact of tobacco advertising and promotion on increasing adolescent smoking
      behaviours.
AB  - BACKGROUND: The tobacco industry denies that their marketing is targeted at young
      nonsmokers, but it seems more probable that tobacco advertising and promotion
      influences the attitudes of nonsmoking adolescents, and makes them more likely to
      try smoking. OBJECTIVES: To assess the effects of tobacco advertising and
      promotion on nonsmoking adolescents' future smoking behaviour. SEARCH STRATEGY:
      We searched the Cochrane Tobacco Group specialized register, the Cochrane Central
      Register of Controlled Trials, MEDLINE, the Cochrane Library, Sociological
      Abstracts, PsycLIT, ERIC, WorldCat, Dissertation Abstracts, ABI Inform and
      Current Contents to August 2002. SELECTION CRITERIA: We selected longitudinal
      studies that assessed individuals' smoking behaviour and exposure to advertising,
      receptivity or attitudes to tobacco advertising, or brand awareness at baseline,
      and assessed smoking behaviour at follow-ups. Participants were adolescents aged
      18 or younger who were not regular smokers at baseline. DATA COLLECTION AND
      ANALYSIS: Studies were prescreened for relevance by one reviewer. Two reviewers
      independently assessed relevant studies for inclusion. Data were extracted by one
      reviewer and checked by a second. MAIN RESULTS: Nine longitudinal studies that
      followed up a total of over 12,000 baseline nonsmokers met inclusion criteria.
      The studies measured exposure or receptivity to advertising and promotion in a
      variety of ways, including having a favourite advertisement or an index of
      receptivity based on awareness of advertising and ownership of a promotional
      item. One study measured the number of tobacco advertisements in magazines read
      by participants. All studies assessed smoking behaviour change in participants
      who reported not smoking at baseline. In all studies the nonsmoking adolescents
      who were more aware of tobacco advertising or receptive to it, were more likely
      to have experimented with cigarettes or become smokers at follow-up. There was
      variation in the strength of association, and the degree to which potential
      confounders were controlled for. REVIEWER'S CONCLUSIONS: Longitudinal studies
      consistently suggest that exposure to tobacco advertising and promotion is
      associated with the likelihood that adolescents will start to smoke. Based on the
      strength of this association, the consistency of findings across numerous
      observational studies, temporality of exposure and smoking behaviours observed,
      as well as the theoretical plausibility regarding the impact of advertising, we
      conclude that tobacco advertising and promotion increases the likelihood that
      adolescents will start to smoke.

PMID- 14583978
TI  - Amino acids for amyotrophic lateral sclerosis / motor neuron disease.
AB  - BACKGROUND: Amyotrophic lateral sclerosis, also known as motor neuron disease, is
      a progressive neuromuscular disease that causes disability and eventual death.
      Various amino acid preparations, the three branched-chain amino acids (L-leucine,
      L-valine and L-isoleucine) or, alternatively, L-threonine have been used as
      experimental therapy. OBJECTIVES: To examine the efficacy of amino acid therapies
      in prolonging survival and/or slowing the progression of amyotrophic lateral
      sclerosis/motor neuron disease. SEARCH STRATEGY: We searched the Cochrane
      Neuromuscular Disease Group trials register (searched February 2003), MEDLINE
      (from January 1966 to December 2002) and EMBASE (from January 1980 to December
      2002) databases and reports of specialist conferences. Authors of known studies
      were contacted. SELECTION CRITERIA: We included randomised or quasi-randomised
      trials of participants with a clinical diagnosis of amyotrophic lateral
      sclerosis/motor neuron disease treated with all combinations of amino acids. Our
      primary outcome measure was survival determined by a pooled hazard ratio of all
      studies. Our secondary outcome measures were (in order of priority): survival at
      six and 12 months, muscle strength, any validated rating scale of physical
      function, quality of life, proportion of patients completing therapy and
      proportion of patients reporting adverse events attributable to treatment. DATA
      COLLECTION AND ANALYSIS: We identified six eligible trials and rejected a further
      seven because of incomplete data or inadequate duration. Eligible studies were
      rated for methodological quality and missing data sought from the authors. After
      this examination two studies were excluded from analysis. Our pooled survival
      analysis was performed by the Parmar method, other statistical calculations were
      done using the Review Manager 4.2 software package. MAIN RESULTS: No benefit
      could be demonstrated for either branched-chain amino acids or L-threonine in
      improving survival in amyotrophic lateral sclerosis/motor neuron disease. Neither
      could we find evidence of an effect of either treatment on muscle strength or
      disability as measured by functional rating scales. No study assessed quality of
      life. Both branched-chain amino acids and L-threonine appeared well tolerated and
      caused a degree of adverse events comparable to that of the control medication.
      REVIEWER'S CONCLUSIONS: There is no evidence to support a beneficial effect of
      either branched-chain amino acids or L-threonine in amyotrophic lateral
      sclerosis/motor neuron disease.

PMID- 14583979
TI  - Antiplatelet and anticoagulation for patients with prosthetic heart valves.
AB  - BACKGROUND: Patients with prosthetic heart valves are at increased risk for valve
      thrombosis and arterial thromboembolism. Oral anticoagulation alone, or the
      addition of antiplatelet drugs, has been used to minimize this risk. An important
      issue is the effectiveness and safety of the latter strategy. OBJECTIVES: To
      compare the effectiveness and safety of adding antiplatelet therapy to standard
      oral anticoagulation among patients with prosthetic heart valves. SEARCH
      STRATEGY: We searched the Cochrane Central Register of Controlled Trials
      (Cochrane Library Issue 2, 2003), MEDLINE (January 1966 to August 2002), EMBASE
      (January 1988 to July 2001) and reference lists of individual reports, review
      articles, meta-analyses, and consensus statements. SELECTION CRITERIA: All
      reports of randomised controlled trials comparing standard dose oral
      anticoagulation to standard dose oral anticoagulation and antiplatelet therapy in
      patients with one or more prosthetic heart valves. We included reports published
      in any language or in abstract form. DATA COLLECTION AND ANALYSIS: Two reviewers
      independently performed the search strategy, assessed trials for inclusion
      criteria, study quality, and extracted data. Adverse effects information was
      collected from the trials. MAIN RESULTS: Eleven studies involving 2,428 subjects
      met the inclusion criteria. Year of publication ranged from 1971 to 2000.
      Compared with anticoagulation alone, the addition of an antiplatelet agent
      reduced the risk of thromboembolic events (odds ratio 0.39 (95% confidence
      interval 0.28 to 0.56; p<0.00001)) and total mortality (odds ratio 0.55 (95%
      confidence interval 0.40 to 0.77; p=0.0003)). Aspirin and dipyridamole reduced
      these events similarly. The risk of major bleeding was increased when
      antiplatelet agents were added to oral anticoagulants (odds ratio 1.66 (95%
      confidence interval 1.18 to 2.34; p=0.003)). For major bleeding, there was no
      evidence of heterogeneity between aspirin and dipyridamole and in the comparison
      of trials performed before and after 1990, around the time when anticoagulation
      standardization with the international normalized ratio was being implemented.
      REVIEWER'S CONCLUSIONS: Adding antiplatelet therapy, either dipyridamole or low
      dose aspirin, to oral anticoagulation decreases the risk of systemic embolism or
      death among patients with prosthetic heart valves. The risk of major bleeding is
      increased with antiplatelet therapy. These results apply to patients with
      mechanical prosthetic valves or those with biological valves and indicators of
      high risk such as atrial fibrillation or prior thromboembolic events. The
      effectiveness and safety of low dose aspirin (100 mg daily) appears to be similar
      to higher dose aspirin and dipyridamole.

PMID- 14583980
TI  - Exercise therapy for patellofemoral pain syndrome.
AB  - BACKGROUND: Patellofemoral pain syndrome (PFPS) is a common problem among
      adolescents and young adults, characterised by retropatellar pain (behind the
      kneecap) or peripatellar pain (around the kneecap) when ascending or descending
      stairs, squatting or sitting with flexed knees. Etiology, structures causing the
      pain and treatment methods are all debated in literature, but consensus has not
      been reached so far. Exercise therapy to strengthen the quadriceps is often
      prescribed, though its efficacy is still debated. OBJECTIVES: This review aims to
      summarise the evidence of effectiveness of exercise therapy in reducing anterior
      knee pain and improving knee function in patients with PFPS. SEARCH STRATEGY: We
      searched the Cochrane Musculoskeletal Injuries Group and Cochrane Rehabilitation
      and Related Therapies Field specialised registers, the Cochrane Controlled Trials
      Register, PEDro - The Physiotherapy Evidence Database, MEDLINE, EMBASE, CINAHL,
      up till December 2001 for controlled trials (randomised or not) comparing
      exercise therapy with control groups, or comparing different types of exercise
      therapy. SELECTION CRITERIA: Only trials focusing on exercise therapy in patients
      with PFPS were considered. Trials in patients with other diagnoses such as
      tendinitis, Osgood Schlatter syndrome, bursitis, traumatic injuries,
      osteoarthritis, plica syndrome, Sinding-Larssen-Johansson syndrome and patellar
      luxations were excluded. DATA COLLECTION AND ANALYSIS: From 750 publications 12
      trials were selected. All included trials studied quadriceps strengthening
      exercises. Outcome assessments for knee pain and knee function in daily life were
      used in a best evidence synthesis to summarise evidence for effectiveness. MAIN
      RESULTS: One high and two low quality studies used a control group not receiving
      exercise therapy. Significantly greater pain reduction in the exercise groups was
      found in one high and one low quality study, though at different time points.
      Only one low quality study reported significantly greater functional improvement
      with exercise. Five studies compared exercise therapies that could be designated
      closed kinetic chain exercise (foot in contact with a surface) versus open
      kinetic chain exercise (foot not in contact with a surface). Two of these studies
      were of high quality, but no significant differences in improvement of function
      or reduction of pain were apparent between the types of exercise in any of the
      studies. The remaining four studies, all of which were of low quality, focused on
      other treatment comparisons. REVIEWER'S CONCLUSIONS: The evidence that exercise
      therapy is more effective in treating PFPS than no exercise was limited with
      respect to pain reduction, and conflicting with respect to functional
      improvement. There is strong evidence that open and closed kinetic chain exercise
      are equally effective. Further research to substantiate the efficacy of exercise
      treatment compared to a non-exercising control group is needed, and thorough
      consideration should be given to methodological aspects of study design and
      reporting.

PMID- 14583981
TI  - Steroid therapy for meconium aspiration syndrome in newborn infants.
AB  - BACKGROUND: Meconium aspiration syndrome may cause severe respiratory distress in
      the newborn infant, with an associated high morbidity and mortality. A chemical
      pneumonitis is believed to occur secondary to bile, bile acids and pancreatic
      secretions contained in meconium. It has therefore been hypothesised that
      corticosteroids may be of benefit in the management of this condition through
      their anti-inflammatory properties. OBJECTIVES: The objective of this review was
      to determine whether steroid therapy for meconium aspiration syndrome decreases
      the morbidity and mortality associated with this condition without adverse
      effects. SEARCH STRATEGY: Searches were made of PREMEDLINE and MEDLINE from 1966
      to April 2003, CINAHL back to 1982, Current Contents back to 1998, The Cochrane
      Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1,
      2003) and Oxford Database of Perinatal Trials. The search included cross
      referencing of previous reviews, and a review of abstracts, conference and
      symposia proceedings published in Pediatric Research from 1993 to 2003. SELECTION
      CRITERIA: Randomised controlled trials and quasi-randomised trials comparing
      steroid treatment to no steroid treatment for neonates with meconium aspiration
      syndrome were considered for this review. DATA COLLECTION AND ANALYSIS: The
      methodological quality of each trial was assessed independently by each author.
      Data were extracted, analysed and results reviewed independently by each author.
      Meta-analysis was performed with RevMan 4.2, using the fixed effects model. Mean
      difference (MD) and weighted mean differences (WMD) with 95% confidence intervals
      in brackets for continuous variables and Relative Risk (RR) with 95% confidence
      intervals for categorical data were reported. MAIN RESULTS: Three randomised
      controlled trials were identified. Two trials, by Wu 1999 (50 participants) and
      Yeh 1977 (35 participants), were included in the review. The trial by Davey 1995,
      as yet unpublished, was excluded from this review as insufficient information
      about methodology and results were available. On meta-analysis, there was no
      significant reduction in mortality [typical RR 0.95 (0.20, 4.58)]. A small but
      significant increase in duration of oxygen therapy was seen with the use of
      steroids [WMD 30.0 hours (8.4, 51.6)]. There was no significant difference in
      duration of hospital stay in the study by Wu 1999 [MD 0.00 days (-3.09, 3.09)].
      Duration of mechanical ventilation was reported by Wu 1999 with no significant
      difference seen [MD -1.10 days (-2.79, 0.59)]. Incidence of air leak was reported
      by Yeh 1977 with no significant difference detected [RR 0.64 (0.18, 2.26)]. Long
      term outcome was not reported in either of the two studies. REVIEWER'S
      CONCLUSIONS: At present, there is insufficient evidence to assess the effects of
      steroid therapy in the management of meconium aspiration syndrome. A further
      large randomised controlled trial assessing potential benefits and harm would be
      required to determine its role.

PMID- 14583982
TI  - Progestogen for preventing miscarriage.
AB  - BACKGROUND: Progesterone, a female sex hormone, is known to induce secretory
      changes in the lining of the uterus essential for successful implantation of a
      fertilized egg. It has been suggested that a causative factor in many cases of
      miscarriage may be inadequate secretion of progestogens. Therefore,
      progestational agents have been used, beginning in the first trimester of
      pregnancy, in an attempt to prevent spontaneous miscarriage. OBJECTIVES: To
      determine the efficacy and safety of progestogens as a preventative therapy
      against miscarriage. SEARCH STRATEGY: We searched the Cochrane Pregnancy and
      Childbirth Group trials register (April 2003), CENTRAL, MEDLINE (1966 to April
      2003), EMBASE (1980 to April 2003), CINAHL (1982 to April 2003), NHMRC Clinical
      Trials Register (April 2003) and Meta-Register (April 2003). We searched
      references from relevant articles, attempting to contact authors where necessary,
      and contacted experts in the field for unpublished works. SELECTION CRITERIA:
      Randomised or quasi-randomised controlled trials comparing progestogens with
      placebo or no treatment given in an effort to prevent miscarriage. DATA
      COLLECTION AND ANALYSIS: Thirty trials were identified in the initial search. At
      least, two reviewers assessed trial quality and extracted data. Data for all
      outcomes were in dichotomous form and the Peto odds ratio was used in the meta
      analysis for all comparisons. MAIN RESULTS: Fourteen trials (1988 women) met the
      inclusion criteria. The meta-analysis of all women, regardless of gravidity and
      number of previous miscarriages, showed no statistically significant difference
      in the risk of miscarriage between progestogen and placebo or no treatment groups
      (odds ratio (OR) 1.05, 95% confidence interval (CI) 0.83 to 1.34) and no
      statistically significant difference in the incidence of adverse effect in either
      mother or baby. In a subgroup analysis of three trials involving women who had
      recurrent miscarriages (three or more consecutive miscarriages), progestogen
      treatment showed a statistically significant decrease in miscarriage rate
      compared to placebo or no treatment (OR 0.39, 95% CI 0.17 to 0.91). No
      statistically significant differences were found between the route of
      administration of progestogen (oral, intramuscular, vaginal) versus placebo or no
      treatment. REVIEWER'S CONCLUSIONS: There is no evidence to support the routine
      use of progestogen to prevent miscarriage in early to mid pregnancy. However,
      further trials in women with a history of recurrent miscarriage may be warranted,
      given the trend for improved live birth rates in these women and the finding of
      no statistically significant difference between treatment and control groups in
      rates of adverse effects suffered by either mother or baby in the available
      evidence.

PMID- 14583983
TI  - Intranasal corticosteroids for asthma control in people with coexisting asthma
      and rhinitis.
AB  - BACKGROUND: Allergic rhinitis and asthma are mediated by similar allergic
      mechanisms. They may represent two manifestations of the same united airway
      disease and therefore intranasal corticosteroids (INCS) could improve asthma.
      Nevertheless none of the asthma guidelines have advocated intranasal
      corticosteroids for asthma. OBJECTIVES: To assess the efficacy of intranasal
      corticosteroids on asthma outcomes in people with rhinitis and asthma. SEARCH
      STRATEGY: We searched the Cochrane Airways Group trials register, the Cochrane
      Central Register of Controlled Trials (Issue 1, 2003), MEDLINE and reference
      lists of articles. We also contacted researchers in the field. Last search
      updated in March 2003. SELECTION CRITERIA: Randomised controlled trials comparing
      intranasal corticosteroids to intranasal placebo or to other traditional asthma
      treatments were included. Intrabronchial corticosteroids were not allowed but a
      device combining intranasal and intrabronchial corticosteroid was considered as
      being a primary INCS technique and was therefore also compared to placebo. DATA
      COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and
      extracted data. Study authors were contacted for additional information. Quality
      assessment for the 14 eligible studies was performed using the Jadad score and by
      ranking allocation concealment. Statistical analysis for continuous data was done
      by weighted mean difference or standardised mean difference. MAIN RESULTS:
      Fourteen trials involving 477 people were included. Meta-analysis for asthma
      outcomes failed to show a statistically significant benefit of INCS in asthma.
      However, for symptom scores and forced expiratory volume in one second, the trend
      favoured a beneficial effect of INCS. For asthma symptom scores (two parallel
      studies), the standardised mean difference was 0.61 (95% confidence interval (CI)
      -0.04 to 1.26). Meta-analysis for forced expiratory volume in one second (five
      parallel studies) gave a standardised mean difference of 0.31 (95% CI -0.04 to
      0.65). In the parallel studies, meta-analysis of peak expiratory flow gave a
      standardised mean difference of -0.10 Litres/min (95% CI -0.55 to 0.35) for mean
      peak flow (three studies). Meta-analysis for methacholine airway responsiveness
      (three parallel studies) showed a standardised mean difference of -0.20 (-95% CI
      0.64 to 0.24). REVIEWER'S CONCLUSIONS: Intranasal corticosteroids were well
      tolerated. While INCS tended to improve asthma symptoms and forced expiratory
      volume in one second, the results did not reach significance. The combination of
      intranasal plus intrabronchial corticosteroids should remain the current clinical
      practice until more research is done.

PMID- 14583984
TI  - Hospital at home for acute exacerbations of chronic obstructive pulmonary
      disease.
AB  - BACKGROUND: Hospital at home schemes are a recently adopted method of service
      delivery for the management of acute exacerbations of chronic obstructive
      pulmonary disease aimed at reducing demand for acute hospital in-patient beds and
      promoting a patient centered approach through admission avoidance. However,
      evidence in support of such a service is contradictory. OBJECTIVES: To evaluate
      the efficacy of "hospital at home" compared to hospital inpatient care in acute
      exacerbations of chronic obstructive pulmonary disease. SEARCH STRATEGY: The
      Cochrane Central Register of Controlled Trials; electronically available
      databases e.g. MEDLINE (1966-current), EMBASE (1980-current), PubMed,
      ClincalTrials, Science Citation Index and on-line individual respiratory
      journals; bibliographies of included trials were all searched and contact with
      authors was made to obtain studies. The most recent searches were carried out in
      August 2003. SELECTION CRITERIA: Only randomised controlled trials were
      considered where patients presented to the emergency department with an
      exacerbation of their chronic obstructive pulmonary disease. Studies must not
      have recruited patients that are usually deemed obligatory admissions. DATA
      COLLECTION AND ANALYSIS: Two reviewers independently selected articles for
      inclusion, evaluated methodological quality of the studies and abstracted data.
      MAIN RESULTS: Seven studies with 754 patients were included in the review.
      Studies provided data on hospital readmission and mortality both of which were
      not significantly different when the two study groups were compared (RR 0.89;
      95%CI 0.72 to 1.12 & RR 0.61; 95%CI 0.36 to 1.05, respectively). Both the
      patients and the carers preferred hospital at home schemes to inpatient care (RR
      1.53; 95%CI 1.23 to 1.90). Other reported outcomes included few studies.
      REVIEWER'S CONCLUSIONS: This review has shown that one in four carefully selected
      patients presenting to hospital emergency departments with acute exacerbations of
      chronic obstructive pulmonary disease can be safely and successfully treated at
      home with support from respiratory nurses. This review found no evidence of
      significant differences between "hospital at home" patients and hospital
      inpatients for readmission rates and mortality at two to three months after the
      initial exacerbation. Both the patients and carers preferred "hospital at home"
      schemes to inpatient care.

PMID- 14583985
TI  - Early extubation for adult cardiac surgical patients.
AB  - BACKGROUND: Over 30 studies reported that early extubation (within eight hours)
      appears to be safe without an increased incidence of morbidity. A benefit of the
      practice may be cost savings associated with shorter Intensive Care Unit and
      hospital length of stays. OBJECTIVES: To assess the effects of early extubation
      and the impact of the extubating clinician's profession on morbidity, mortality,
      intensive care unit and hospital length of stay, with a subgroup analysis for
      extubation within four hours or four to eight hours. SEARCH STRATEGY: We searched
      the Cochrane Central Register of Controlled Trials (CENTRAL)(issue 1, 2003),
      MEDLINE (January 1966 to June 2003), EMBASE (January 1980 to June 2003), CINAHL
      (January 1982 to December 2002), SIGLE(January 1980 to December 2002). We
      searched reference lists of articles and contacted researchers in the field.
      SELECTION CRITERIA: Randomized controlled trials and controlled clinical trials
      of adult cardiac surgical patients (coronary artery bypass grafts, aortic valve
      replacement, mitral valve replacement, aortic aneurysm repair). DATA COLLECTION
      AND ANALYSIS: Two reviewers independently assessed trial quality and extracted
      data. Study authors were contacted for additional information. A meta-analysis
      for most outcomes was conducted. MAIN RESULTS: Six trials were included in the
      review. There was no evidence of a difference between early and conventionally
      extubated patients shown in the relative risk and 95% confidence interval for the
      following outcomes: mortality in intensive care was 0.8 (0.42 to 1.52); thirty
      day mortality was 1.2 (0.63 to 2.27); myocardial ischaemia was 0.96 (0.71 to
      1.30); reintubation within 24 hours of surgery was 5.93 (0.72 to 49.14). Time
      spent in intensive care and in hospital were significantly shorter for patients
      extubated early (7.02 hours (- 7.42 to - 6.61) and 1.08 days ( - 1.35 to - 0.82)
      respectively). REVIEWER'S CONCLUSIONS: There is no evidence of a difference in
      mortality and morbidity rates between the study groups. Early extubation reduces
      intensive care unit and hospital length of stay. Studies were underpowered and
      designed to show differences between study groups rather than equivalence between
      the groups. Suggested future areas of investigation: establishing the safety and
      efficacy of immediate extubation compared with early extubation; establishing the
      most effective means of pain control and reducing anxiety for patients;
      systematic reviews of the evidence for different parts of the patients journey
      through a cardiac surgery episode; and the impact of the profession of the
      clinician making the decision to extubate.

PMID- 14583986
TI  - Modification of the home environment for the reduction of injuries.
AB  - BACKGROUND: Injury in the home is extremely common, accounting for around a third
      of all injuries. The majority of injuries of children under five and people aged
      75 and over occur at home. Multi-factorial injury prevention interventions have
      been shown to reduce injuries in the home. However, few studies have focussed
      specifically on the impact of physical adaptations to the home environment and
      the effectiveness of such intervention needs to be ascertained. OBJECTIVES: To
      review the evidence for the effect on injuries of modification of the home
      environment with a primary focus on interventions to reduce physical hazards.
      SEARCH STRATEGY: We searched the following databases: APId, ASSIA, British
      Nursing Index, CINAHL, Cochrane Library databases, Dissertation Abstracts,
      EMBASE, HealthSTAR, ICONDA, ISI Science (and Social Science) Citation Index,
      MEDLINE, National Research Register, PREMEDLINE, SIGLE and Urbadisk. Conference
      proceedings and reference lists were scanned. Experts in the field and trialists
      were contacted. Searches were not restricted to English language. Handsearching
      of relevant journals was not conducted. SELECTION CRITERIA: Randomised controlled
      trials, non-randomised controlled trials, controlled before-and-after studies and
      interrupted time series studies. DATA COLLECTION AND ANALYSIS: All abstracts were
      screened by two reviewers for relevance, outcome and design. Two reviewers
      independently evaluated methodological quality and extracted data from each
      eligible study. MAIN RESULTS: We found 28 published trials and one unpublished
      study. Trials were not sufficiently similar to allow for the combination of data
      by statistical analyses, so this review takes a narrative form. Studies were
      divided into three groups based on the primary population sample: children, older
      people and the general population. None of the 11 childhood studies demonstrated
      a reduction in injuries that might have been due to environmental adaptation in
      the home. One study reported a reduction in injuries and in hazards but the two
      could not be linked. The majority of studies used hazard reduction as the
      outcome. Of the 15 studies in older people, none demonstrated a reduction in
      injuries due to hazard reduction, although two demonstrated a reduction in falls
      that could be due to hazard reduction. In the mixed age group there were two
      trials; neither demonstrated an effect on injuries. REVIEWER'S CONCLUSIONS: There
      is insufficient evidence to determine the effects of interventions to modify
      environmental home hazards. Further interventions to reduce hazards in the home
      should be evaluated by adequately designed randomised controlled trials measuring
      injury outcomes. Recruitment of large study samples to measure effect may be a
      major consideration for future trials.

PMID- 14583987
TI  - Formulas containing hydrolysed protein for prevention of allergy and food
      intolerance in infants.
AB  - BACKGROUND: Allergies and food reactions are common and may be associated with
      foods including adapted cow's milk formulas. Formulas containing hydrolysed
      proteins have been used to treat infants with allergy or food intolerance, and
      have been advocated for prevention of allergy and food intolerance in infants.
      OBJECTIVES: To determine whether use of hydrolysed formulas for infant feeding
      prevents allergy and food intolerance. If hydrolysed formulas are effective, to
      determine what type of hydrolysed formula is most effective including extensively
      and partially hydrolysed formulas. To determine which infants benefit including
      infants at low or high risk of allergy and infants receiving early, short term or
      prolonged formula feeding. SEARCH STRATEGY: The standard search strategy of the
      Cochrane Neonatal Review Group was used including searches of the Cochrane
      Controlled Trials Register (2003, Issue 1), MEDLINE (1966 - January 2003), EMBASE
      (1980 - January 2003) and CINAHL (1982 - January 2003) and previous reviews
      including cross references. SELECTION CRITERIA: Randomised and quasi-randomised
      trials that compare the use of a hydrolysed infant formula to human milk or cow's
      milk formula. Trials with >80% follow up of participants were eligible for
      inclusion. DATA COLLECTION AND ANALYSIS: Eligibility of studies for inclusion,
      methodological quality and data extraction were assessed independently by each
      reviewer. Primary outcomes included clinical allergy, specific allergies and food
      intolerance. Meta-analysis was conducted using a fixed effects model. MAIN
      RESULTS: Eighteen trials met criteria for inclusion. No eligible trials compared
      prolonged hydrolysed formula to human milk feeding. Two trials compared early,
      short term hydrolysed formula to human milk feeding and reported no significant
      difference in infant allergy or childhood cow's milk allergy (CMA). Two trials
      compared early, short term hydrolysed formula to cow's milk formula feeding with
      no significant benefits reported. One large quasi-random study reported a
      reduction in infant CMA of borderline significance in low risk infants (RR 0.62,
      95% CI 0.38, 1.00).Seven studies compared prolonged feeding of hydrolysed formula
      to cow's milk formula without using co-interventions for allergy prevention. Meta
      analysis of 4 studies (386 infants) found a significant reduction in allergy
      incidence in infancy (typical RR 0.63, 95% CI 0.47, 0.85; RD -0.15, 95% CI -0.25,
      -0.06). One study reported a significant reduction in allergy incidence in
      childhood (RR 0.54, 95% CI 0.36, 0.81). Significant reductions were found in
      asthma prevalence in childhood, eczema incidence in infancy and prevalence in
      childhood, food allergy prevalence in childhood, and CMA incidence in infancy.
      All studies enrolled infants at high risk of allergy. Only three trials comparing
      prolonged hydrolysed formula feeding to cow's milk formula feeding were
      considered of good methodology. Only one of these trials demonstrated a benefit
      into childhood (5 years of age). No eligible trials examined the effects of
      prolonged hydrolysed formula feeding on allergy beyond early childhood. Costs
      were not reported. Three trials compared prolonged feeding with an extensive to a
      partially hydrolysed formula and reported no significant difference in allergy
      incidence in infancy. REVIEWER'S CONCLUSIONS: There is no evidence to support
      feeding with a hydrolysed formula for the prevention of allergy in preference to
      exclusive breast feeding. In high risk infants who are unable to be completely
      breast fed, there is evidence that prolonged feeding with a hydrolysed compared
      to a cow's milk formula reduces infant and childhood allergy and infant CMA.
      Further trials are required to determine if significant clinical benefits persist
      beyond 5 years of age and if there is any additional benefit from use of an
      extensive compared to a partially hydrolysed formula. Incremental costs of
      formula and the effect on compliance should be measured.

PMID- 14583988
TI  - Vitamin E supplementation for prevention of morbidity and mortality in preterm
      infants.
AB  - BACKGROUND: Treating very low birth weight (VLBW) infants with pharmacologic
      doses of vitamin E as an antioxidant agent has been proposed for preventing or
      limiting retinopathy of prematurity, intracranial hemorrhage, hemolytic anemia,
      and chronic lung disease. However, excessive doses of vitamin E may result in
      side effects. OBJECTIVES: The aim of this systematic review was to assess the
      effects of vitamin E supplementation on morbidity and mortality in preterm
      infants. SEARCH STRATEGY: We searched MEDLINE (October 2002), EMBASE (March
      2002), the Cochrane Controlled Trials Register (CCTR) from the Cochrane Library,
      2003, Issue 1, and personal files for clinical trials assessing vitamin E in
      preterm infants. SELECTION CRITERIA: We selected trials analyzing primary
      outcomes (mortality or combined long-term morbidity) or secondary outcomes (other
      morbidity) in infants with gestational age less than 37 weeks or birth weight
      less than 2500 grams. The intervention was allocation to routine supplementation
      with vitamin E in the treatment group versus placebo, no treatment or another
      type, dose or route of administration of vitamin E. DATA COLLECTION AND ANALYSIS:
      We used standard methods of the Cochrane Collaboration and of the Cochrane
      Neonatal Review Group. MAIN RESULTS: Twenty-six randomized clinical trials
      fulfilled entry criteria. No study assessed combined long-term morbidity. Routine
      vitamin E supplementation significantly increased hemoglobin concentration by a
      small amount. Vitamin E significantly reduced the risk of germinal
      matrix/intraventricular hemorrhage and increased the risk of sepsis; however,
      heterogeneity limits the strength of these latter two inferences. Vitamin E did
      not significantly affect other morbidity or mortality. In VLBW infants, vitamin E
      supplementation significantly increased the risk of sepsis, and reduced the risk
      of severe retinopathy and blindness among those examined. Subgroup analyses
      showed (1) an association between intravenous, high-dose vitamin E
      supplementation and increased risk of sepsis and of parenchymal cerebral
      hemorrhage; (2) an association between vitamin E supplementation by other than
      the intravenous route and reduced risk of germinal matrix-intraventricular
      hemorrhage and of severe intraventricular hemorrhage; and (3) an association
      between serum tocopherol levels greater than 3.5 mg/dl and increased risk of
      sepsis and reduced risk for severe retinopathy among those examined. REVIEWER'S
      CONCLUSIONS: Vitamin E supplementation in preterm infants reduced the risk of
      intracranial hemorrhage but increased the risk of sepsis. In very low birth
      weight infants it increased the risk of sepsis, and reduced the risk of severe
      retinopathy and blindness among those examined. Evidence does not support the
      routine use of vitamin E supplementation by intravenous route at high doses, or
      aiming at serum tocopherol levels greater than 3.5 mg/dl.

PMID- 14583989
TI  - Anticoagulant and aspirin prophylaxis for preventing thromboembolism after major
      gynaecological surgery.
AB  - BACKGROUND: The reported overall risk of deep venous thrombosis in gynaecological
      surgery ranges from 7 to 45%. Fatal pulmonary embolism is estimated to occur in
      nearly 1% of these women. Pharmaceutical interventions are one possible
      prophylactic measure for preventing emboli in women undergoing major
      gynaecological surgery. Agents include unfractionated heparin (low -dose and
      adjusted-dose), low-molecular-weight heparins, heparinoids and warfarin.
      OBJECTIVES: The objective of this review was to evaluate the effectiveness of
      warfarin, heparin and aspirin in preventing thromboembolism after major
      gynaecological surgery. SEARCH STRATEGY: We searched the Cochrane Menstrual
      Disorders and Subfertility Group trials register (searched 15 August 2003), the
      Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library issue
      2, 2003), MEDLINE (1966 to April 2003), EMBASE (1985 to April 2003), and CINAHL
      (1982 to April 2003). References from relevant articles were searched and authors
      contacted where necessary. In addition we contacted experts in the field for
      unpublished works. SELECTION CRITERIA: Randomised controlled trials of heparins,
      warfarin or aspirin to prevent thromboembolism after major gynaecological surgery
      were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Thirty-three trials
      were identified in the initial search. On careful inspection only eight of these
      met the inclusion criteria. Trials were data extracted and assessed for quality
      by at least two reviewers. Data were combined for meta-analysis using odds ratios
      for dichotomous data or weighted mean difference for continuous data. A random
      effects statistical model was used. MAIN RESULTS: The meta-analysis of heparin
      versus placebo found a statistically significant decrease in the number of DVTs
      in both the all women group (including those with and without malignancy) (OR
      0.30, 95% CI 0.12 to 0.76) and the subgroup of only women with malignancy (OR
      0.30, 95% CI 0.10 to 0.89). There was no significant difference in the incidence
      of PE. Oral warfarin reduced DVT when compared to placebo in all women (OR 0.22,
      95% CI 0.06 to 0.86) and in women with malignancy (OR 0.18, 95% CI 0.04 to 0.87).
      Meta-analyses of UH and LMWH showed no statistical difference in any comparison.
      No studies compared aspirin alone to placebo, heparin or warfarin. There was a
      statistically significant increase in injection site haematomas associated with
      heparin compared to placebo (OR 0.30, 95% CI 0.10 to 0.89). REVIEWER'S
      CONCLUSIONS: Women, undergoing major gynaecological surgery and without
      contraindications to anticoagulants should be offered thromboprophylaxis.
      Evidence suggests that UH and LMWH are equally as effective in preventing DVT and
      the one trial available suggests that warfarin is as effective as UH. There is no
      evidence as yet to suggest that warfarin, heparin or aspirin reduce incidence of
      PE.

PMID- 14583990
TI  - Written and verbal information versus verbal information only for patients being
      discharged from acute hospital settings to home.
AB  - BACKGROUND: It is becoming commonplace for patients to be discharged earlier from
      acute hospital settings to their own homes and be required to manage various
      aspects of their own care. This has increased the need for detailed information
      to be given to patients and/or significant others to enable them to effectively
      manage care at home. It has been suggested that providing written health
      information can assist in this self management. OBJECTIVES: To determine the
      effectiveness of providing written health information in addition to verbal
      information for patients and/or significant others being discharged from acute
      hospital settings to home. SEARCH STRATEGY: Computerised searches from 1990 to
      June 2002 of the Cochrane Consumers and Communication Review Group Specialised
      Register and Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE
      (OVID), EMBASE, CINAHL, PsycINFO, ERIC, OVID (including Ageline, EBM Reviews,
      DARE, Best Evidence, Pre-MEDLINE and PsycARTICLES), Sociological abstracts,
      Austhealth and bibliographies in articles that met inclusion criteria. SELECTION
      CRITERIA: Articles were selected if they were randomised control trials or
      controlled clinical trials; included patients discharged from acute hospital
      settings to home; the patient and/or significant others received written health
      information and verbal information in the intervention group, and verbal
      information only in the control group; and the intervention (written health
      information and verbal information) was provided at discharge. DATA COLLECTION
      AND ANALYSIS: Two reviewers independently screened abstracts to determine
      relevance. Relevant full paper copies were then reviewed against the inclusion
      criteria. The findings were extracted by one reviewer and confirmed by the other
      reviewer. The two trials that met the inclusion criteria were too disparate to
      warrant meta-analysis. MAIN RESULTS: The participants in the two trials were
      parents of children who were discharged from children's hospitals, one in the
      United States (n=197) the other in Canada (n=123). Provision of verbal and
      written health information significantly increased knowledge and satisfaction
      scores. REVIEWER'S CONCLUSIONS: This review recommends the use of both verbal and
      written health information when communicating about care issues with patients
      and/or significant others on discharge from hospital to home. The combination of
      verbal and written health information enables the provision of standardised care
      information to patients and/or significant others, which appears to improve
      knowledge and satisfaction. Many of our objectives could not be addressed in this
      review due to lack of trials which met the review's inclusion criteria. There is
      therefore scope for future research to investigate the effects of providing
      verbal and written health information on readmission rates, recovery time,
      complication rates, costs of health care, consumers' confidence level, stress and
      anxiety and adherence to recommended treatment and staff training in the delivery
      of verbal and written information. In addition there are other factors which
      impact on the effectiveness of information provided that were not considered in
      this review but are worthy of a separate systematic review, such as the impact of
      the patient and/or significant others being involved in the development of the
      written information, and cultural issues around development and provision of
      information. Due to concerns about literacy levels for some population groups,
      other systematic reviews should also focus on other modes of delivery of
      information besides the written format.

PMID- 14583991
TI  - Early discharge with home support of gavage feeding for stable preterm infants
      who have not established full oral feeds.
AB  - BACKGROUND: Early discharge of stable preterm infants still requiring gavage
      feeds has the potential benefits of uniting families sooner and reducing health
      care and family costs compared to discharge home when on full sucking feeds.
      Potential disadvantages include the increased burden for the family and the
      possibility of complications related to gavage feeding. OBJECTIVES: To determine
      the effects of a policy of early discharge of stable preterm infants with home
      support of gavage feeding compared with a policy of discharge of such infants
      when they have reached full sucking feeds. SEARCH STRATEGY: The standard search
      strategy of the Cochrane Neonatal Review Group was used together with additional
      searches of the Cochrane Central Register of Controlled Trials (The Cochrane
      Library, Issue 1, 2003), CINAHL (1982 to April week 1 2003), EMBASE (1980 to 2003
      week 15) and MEDLINE (1966 to April week 1 2003). SELECTION CRITERIA: All
      randomised and quasi-randomised trials among infants born <37 weeks and requiring
      no intravenous nutrition at the point of discharge were included. Trials were
      required to compare early discharge home with gavage feeds and health care
      support with later discharge home when full sucking feeds were attained. DATA
      COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and
      extracted data. Study authors were contacted for additional information. Data
      analysis was done in accordance with the standards of the Cochrane Neonatal
      Review Group. MAIN RESULTS: Data from one quasi-randomised trial, with 88 infants
      from 75 families, were included in the review. Infants in the early discharge
      program with home gavage feeding had a mean hospital stay that was 9.3 days
      shorter [MD -9.3 (-18.49 to -0.11)] than infants in the control group. Infants in
      the early discharge program also had a lower risk of clinical infection during
      the home gavage period compared with the corresponding time in hospital for the
      control group [RR 0.35 (0.17 to 0.69)]. There were no significant differences
      between groups in duration and extent of breast feeding, weight gain, re
      admission within the first 12 months post discharge from the home gavage program
      or from hospital, scores reflecting parental satisfaction, or health service use.
      REVIEWER'S CONCLUSIONS: Experimental evidence to evaluate the benefits and risks
      in preterm infants of early discharge from hospital with home gavage feeding
      compared with later discharge upon attainment of full sucking feeds is limited to
      the results of one small quasi-randomised controlled trial. High quality trials
      with concealed allocation, complete follow-up of all randomised infants and
      adequate sample size are needed before practice recommendations can be made.

PMID- 14583992
TI  - Erythromycin for the prevention of chronic lung disease in intubated preterm
      infants at risk for, or colonized or infected with Ureaplasma urealyticum.
AB  - BACKGROUND: Controversy exists over whether or not Ureaplasma urealyticum
      colonization or infection of the respiratory tract contributes to the severity of
      chronic lung disease (CLD), a major cause of morbidity and mortality in preterm
      infants. OBJECTIVES: To evaluate the efficacy and safety of prophylactic or
      therapeutic erythromycin in preventing chronic lung disease in intubated preterm
      infants with unknown U. urealyticum status or proven positivity. SEARCH STRATEGY:
      Searches were done of MEDLINE (1966-June 9, 2003), EMBASE (1980-May 5, 2003), The
      Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library,
      Issue 4, 2002), previous reviews including cross-references, and abstracts of
      conference proceedings (Pediatric Academic Societies 2000-2003, American Thoracic
      Society 2001-2003). There were no language restrictions. Expert informants were
      contacted. SELECTION CRITERIA: Randomized or quasi-randomized studies comparing
      either prophylactic or therapeutic administration of oral or intravenous
      erythromycin (regardless of dose and duration) versus no treatment or placebo
      among intubated preterm infants <37 weeks and <2500 grams with either unknown U.
      urealyticum status or proven positivity by culture or polymerase chain reaction.
      DATA COLLECTION AND ANALYSIS: Data were extracted by all of the authors
      independently and differences were resolved by consensus. Treatment effects for
      categorical outcomes were expressed as relative risk, with 95% confidence
      intervals. MAIN RESULTS: Two small controlled studies, both involving intubated
      babies <30 weeks gestation, were eligible for inclusion. Lyon 1998 tested
      prophylactic erythromycin in babies whose U. urealyticum status was unknown at
      the time of initiation of treatment. Jonsson 1998 tested erythromycin in babies
      known to be culture positive for U. urealyticum. Neither trial showed a
      statistically significant effect of erythromycin on CLD, death or the combined
      outcome CLD or death. Because the two studies differed importantly in their
      design, the results were not combined in meta-analyses. No adverse effects of a 7
      10 day course of erythromycin were reported in either study. REVIEWER'S
      CONCLUSIONS: Current evidence does not demonstrate a reduction in CLD/death when
      intubated preterm infants are treated with erythromycin prophylactically before
      U. urealyticum culture/PCR results are known or when Ureaplasma colonized,
      intubated preterm infants are treated with erythromycin. However, a true benefit
      could easily have been missed with the small sample sizes in the two eligible
      studies. The studies were greatly underpowered to detect uncommon adverse effects
      such as pyloric stenosis. Additional controlled trials are required to determine
      whether antibiotic therapy of Ureaplasma reduces CLD and/or death in intubated
      preterm infants.

PMID- 14583993
TI  - Inspiratory muscle training for asthma.
AB  - BACKGROUND: In moderate to severe chronic obstructive pulmonary disease there is
      good evidence of a generalised loss of muscle bulk (including the respiratory
      muscles). It is possible that similar loss of respiratory muscle strength occur
      particularly in more severe asthma related in part to the effects of steroid
      therapy. Thus the respiratory muscle function may well be of relevance in asthma
      and if dysfunctional, may be a suitable target for training. OBJECTIVES: To
      evaluate the efficacy of inspiratory muscle training with an external resistive
      device in patients with asthma. SEARCH STRATEGY: We searched the Cochrane Central
      Register of Controlled Trials (The Cochrane Library Issue 1, 2002), MEDLINE
      (January 1966 to March 2002), EMBASE (January 1985 to March 2002), CINAHL (to
      March 2002) and the UK National Research Register of trials (January 1982 to
      March 2002) and reference lists of articles. We also searched on line respiratory
      journals and contacted manufacturers of training devices to obtain trials.
      SELECTION CRITERIA: All randomised-controlled trials that involved the use of an
      external inspiratory muscle training device versus a control (sham or no
      inspiratory training device) were considered for inclusion. DATA COLLECTION AND
      ANALYSIS: Two reviewers independently selected articles for inclusion, evaluated
      methodological quality of the studies and abstracted data. MAIN RESULTS: Five
      studies were included in the review with four of the studies being produced by
      the same group. PI(max) (maximum inspiratory pressure) reported in three studies
      with 76 patients showed significant improvement with inspiratory muscle training
      when compared to the control group (WMD 23.07 cmH(2)O, 95%CI 15.65 to 30.50).
      Unfortunately, due to the paucity of included studies and data no other outcome
      was reported by more than one study. Therefore it is not possible to confirm
      whether this increase seen with PI(max) translates into any measurable clinical
      benefit. REVIEWER'S CONCLUSIONS: Currently there is insufficient evidence to
      suggest that inspiratory muscle training provides any clinical benefit to
      patients with asthma. Due to the limited availability of studies in this area
      there is a need for further trials evaluating the efficacy of inspiratory muscle
      training devices in patients with asthma. These studies should investigate
      asthmatics with a range of severity. They should investigate clinically relevant
      outcomes such as lung function, symptoms, exacerbation rate and concomitant
      medications.

PMID- 14583994
TI  - Combined corticosteroid and longacting beta-agonist in one inhaler for chronic
      obstructive pulmonary disease.
AB  - BACKGROUND: Long-acting beta-agonists and inhaled corticosteroids have been
      recommended in guidelines for the treatment of chronic obstructive pulmonary
      disease. However, they have only been available until recently via separate
      administration. They have been developed in order to facilitate adherence to
      medication regimens, and to improve efficacy. OBJECTIVES: To assess the efficacy
      of combined inhaled corticosteroid and long-acting beta-agonist preparations in
      the treatment of adults with chronic obstructive pulmonary disease. SEARCH
      STRATEGY: We searched the Cochrane Airways Group chronic obstructive pulmonary
      disease (COPD) trials register (March 2003), the Cochrane Central Register of
      Controlled Trials (The Cochrane Library Issue 1, 2003), LILACS (all years to
      March 2003) and reference lists of articles. We also contacted manufacturers and
      researchers in the field. SELECTION CRITERIA: Studies were included if they were
      randomised, with adequate blinding procedures in place. Studies could compare a
      combined inhaled corticosteroids and long-acting beta-agonist preparation with
      either component preparation or placebo. Studies comparing different members of
      each class of combined therapies were included DATA COLLECTION AND ANALYSIS: Two
      reviewers independently assessed trial quality and extracted data. MAIN RESULTS:
      Four randomised trials with 2986 participants were included. Two different
      combination preparations (fluticasone/salmeterol and budesonide/formoterol) were
      studied in the trials. No meta-analysis on clinical outcomes was possible due to
      different outcome assessment across studies. All studies demonstrated a reduction
      in exacerbation rates versus placebo. Budesonide/formoterol was more effective
      than formoterol in reducing exacerbations in one study from 1.84 to 1.42
      exacerbations per year. Fluticasone/salmeterol did not significantly reduce
      exacerbations compared with either of its component treatments.
      Fluticasone/salmeterol led to better quality of life compared with placebo (two
      studies), although there were conflicting results when compared with inhaled
      corticosteroid alone (two studies). There was no significant difference between
      fluticasone/salmeterol and long-acting beta-agonist (two studies).
      Budesonide/formoterol led to statistically significant differences in quality of
      life compared with placebo, but not when compared with component inhaled
      corticosteroid or beta-agonist (one study). REVIEWER'S CONCLUSIONS: For the
      primary outcome of exacerbations, budesonide/formoterol had a modest advantage
      over a component medication, formoterol, in a single trial, but
      fluticasone/salmeterol did not result in a significant reduction in exacerbations
      compared to either of its components. The combination of steroids and long-acting
      beta-agonist in one inhaler was effective in improving symptoms compared with
      placebo and on certain clinical outcomes compared with one of the individual
      components alone. In order to draw firmer conclusions about the effects of
      combination therapy in a single inhaler more data are necessary, including the
      assessment of the comparative effects with separate administration of the two
      drugs in double-dummy trials.

PMID- 14583995
TI  - Gauze and tape and transparent polyurethane dressings for central venous
      catheters.
AB  - BACKGROUND: Central venous catheters facilitate venous access, allowing the
      intravenous administration of complex drug treatments, blood products and
      nutritional support, without the trauma associated with repeated venepuncture.
      However, central venous catheters are associated with a risk of infection. Some
      studies have indicated that the type of dressing used for central venous
      catheters may affect the risk of infection. Gauze and tape or transparent
      polyurethane film dressings such as Tegaderm, Opsite or Opsite IV3000 are the
      most common types of dressing used to secure central venous catheters. Currently,
      it is not clear which type of dressing is the most appropriate. OBJECTIVES: To
      compare gauze and tape and transparent polyurethane central venous catheter
      dressings in terms of catheter related infection, catheter security, tolerance to
      dressing material and dressing condition in hospitalised adults and children.
      SEARCH STRATEGY: The Cochrane Wounds Group Specialised Trials Register (October
      2002), the Cochrane Controlled Trials Register (4th Quarter 2002) and the
      databases; MEDLINE (1966-December 2002, CINAHL (1982-October 2002) and EMBASE
      (1980-December 2002) were searched to identify any randomised controlled trials
      comparing the effects of gauze and tape and/or transparent polyurethane dressings
      for central venous catheter sites. Additional references were identified from
      bibliographies of published literature and were also sought from other sources.
      SELECTION CRITERIA: All randomised controlled trials evaluating the effects of
      dressing type (i.e. gauze and tape and/or transparent polyurethane dressings) on
      central venous catheter related infection, catheter security, tolerance to
      dressing material and dressing condition in hospitalised patients. DATA
      COLLECTION AND ANALYSIS: Twenty-three studies were reviewed. Data was extracted
      from each paper by two members of the review team independently and results then
      compared. Differences were resolved either by consensus or by referral to a third
      member of the review team. Authors were contacted for missing information. MAIN
      RESULTS: Of the 23 studies reviewed, 14 were excluded. Nine studies were
      included. Data was only available for meta-analysis from six of the nine included
      studies. Of the six included studies with available data, two compared gauze and
      tape with Opsite IV3000, two compared Opsite with Opsite IV3000, one compared
      gauze and tape with Tegaderm, and one compared Tegaderm with Opsite. There was no
      evidence of any difference in the incidence of infectious complications between
      any of the dressing types compared in this review. Each of these comparisons was
      based on no more than two studies and all of these studies reported data from a
      small patient sample. Therefore it is probable that the finding of no difference
      between dressing types is due to the lack of adequate data. REVIEWER'S
      CONCLUSIONS: There is a high level of uncertainty regarding the risk of infection
      with the central venous catheter dressings identified in this review. Therefore,
      at this stage it appears that the choice of dressing for central venous catheters
      can be based on patient preference. To identify the most appropriate central
      venous catheter dressings, further research is necessary. It is paramount that
      any future studies investigating this issue must be rigorously performed
      randomised controlled trials.

PMID- 14583996
TI  - Eradication therapy for peptic ulcer disease in Helicobacter pylori positive
      patients.
AB  - BACKGROUND: Peptic ulcer disease is the cause for dyspepsia in about 10% of
      patients. 95% of duodenal and 70% of gastric ulcers are associated with
      Helicobacter pylori. Eradication of H pylori reduces the relapse rate of ulcers
      but the magnitude of this effect is uncertain. OBJECTIVES: The primary outcomes
      were the proportion of peptic ulcers healed initially and proportion of patients
      free from relapse following successful healing. Eradication therapy was compared
      to placebo or pharmacological therapies in H. pylori positive patients. Secondary
      aims included symptom relief and adverse effects. SEARCH STRATEGY: A search was
      undertaken according to the Cochrane Upper Gastrointestinal and Pancreatic
      Diseases Review Group module using CCTR, MEDLINE, EMBASE and CINAHL databases.
      Experts in the field and pharmaceutical companies were contacted. Abstract books
      between 1994 and 2002 were hand-searched. SELECTION CRITERIA: Randomised
      controlled trials of short and long-term treatment of peptic ulcer disease in H.
      pylori positive adults were analysed. Patients received at least one week of H
      pylori eradication compared with ulcer healing drug, placebo or not treatment.
      Trials were included if they reported assessment from 2 weeks onwards. DATA
      COLLECTION AND ANALYSIS: Data were collected on ulcer healing, recurrence, relief
      of symptoms and adverse effects. MAIN RESULTS: 59 trials were eligible. Data
      extraction was not possible in 7 trials, and 52 trials were included. In duodenal
      ulcer healing, eradication therapy was superior to ulcer healing drug (UHD) (34
      trials, 3910 patients, relative risk [RR] of ulcer persisting = 0.66; 95%
      confidence interval [CI] = 0.58, 0.76) and no treatment (2 trials, 207 patients,
      RR = 0.37; 95% CI 0.26, 0.53). In gastric ulcer healing, no significant
      differences were detected between eradication therapy and UHD (13 trials, 1469
      patients, RR = 1.32; 95% CI = 0.92, 1.90). In preventing duodenal ulcer
      recurrence no significant differences were detected between eradication therapy
      and maintenance therapy with UHD (4 trials, 319 patients, relative risk [RR] of
      ulcer recurring = 0.73; 95% CI = 0.42, 1.25), but eradication therapy was
      superior to no treatment (26 trials 2434 patients, RR = 0.19; 95% CI = 0.15,
      0.26). In preventing gastric ulcer recurrence, eradication therapy was superior
      to no treatment (9 trials, 774 patients, RR = 0.31; 95% CI 0.19, 0.48).
      REVIEWER'S CONCLUSIONS: A 1 to 2 weeks course of H. pylori eradication therapy is
      an effective treatment for H. pylori positive peptic ulcer disease.

PMID- 14583997
TI  - Oral morphine for cancer pain.
AB  - BACKGROUND: Morphine has been used to relieve pain for many years. Oral morphine
      in either immediate release or sustained release form remains the analgesic of
      choice for moderate or severe cancer pain. OBJECTIVES: To determine the efficacy
      of oral morphine in relieving cancer pain. To assess the incidence and severity
      of adverse effects. SEARCH STRATEGY: The following databases were searched: The
      Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Library, Issue
      4, 2002; the trials register of the Cochrane Pain, Palliative and Supportive Care
      group (February 2002); MEDLINE 1966 to December 2002; EMBASE 1988 to December
      2002; and the Oxford Pain Relief database 1950 to 1994. SELECTION CRITERIA:
      Published randomised controlled trials (full reports) reporting on the analgesic
      effect of oral morphine in adults and children with cancer pain. Any comparator
      trials were considered. Trials with fewer than 10 subjects were excluded. DATA
      COLLECTION AND ANALYSIS: One reviewer extracted data, and the findings were
      checked by two other reviewers. There were insufficient comparable data for meta
      analysis to be undertaken, or to produce numbers-needed-to-treat (NNT) for the
      analgesic effect. MAIN RESULTS: Forty five studies (3061 subjects) met the
      inclusion criteria. Fourteen studies compared oral sustained release morphine
      (MSR) preparations with immediate release morphine (MIR). Eight studies compared
      MSR and MSR in different strengths. Nine studies compared MSR with other opioids.
      Five studies compared MIR with other opioids. Two studies compared oral MSR with
      rectal MSR. One study was found comparing each of the following: MSR tablet with
      MSR suspension; MSR with MSR at different dose frequencies; MSR with non-opioids;
      MIR with non-opioids; oral morphine with epidural morphine; and MIR with MIR by a
      different route of administration. Morphine was shown to be an effective
      analgesic. Pain relief did not differ between MSR and MIR. Sustained release
      versions of morphine were effective for 12 or 24 hour dosing depending on the
      formulation. Adverse effects were common but only 4% of patients discontinued
      treatment because of intolerable adverse effects. REVIEWER'S CONCLUSIONS: The
      randomised trial literature for morphine is small given the importance of this
      medicine. Most trials recruited fewer than 100 participants, and did not provide
      appropriate data for meta-analysis. Trial design was frequently based on
      titration of morphine or comparator to achieve adequate analgesia, then crossing
      subjects over in crossover design studies. It is not clear if these trials are
      sufficiently powered to detect any clinical differences between formulations or
      comparator drugs.

PMID- 14583998
TI  - Individual psychotherapy in the outpatient treatment of adults with anorexia
      nervosa.
AB  - BACKGROUND: Anorexia nervosa is a disorder of high morbidity and significant
      mortality. It is commonest in young adult women, in whom the incidence may be
      increasing. The focus of treatment has moved to an outpatient setting and a
      number of differing psychotherapies are presently used in treatment. OBJECTIVES:
      The aim of the present review was to evaluate the evidence from randomised
      controlled trials for the efficacy of outpatient psychotherapies used in the
      treatment of older adolescents and adults with anorexia nervosa SEARCH STRATEGY:
      The strategy comprised database searches of MEDLINE, EXTRAMED, EMBASE,PSYCLIT,
      CURRENT CONTENTS, Cochrane Collaboration Controlled Trials Register and the
      Depression and Anxiety Neuroses Cochrane Group (CCDAN), a hand-search of The
      International Journal of Eating Disorders, and he reference lists of all papers
      selected. Personal letters were sent to identified notable researchers published
      in the area, requesting information on trials that are unpublished or in
      progress. SELECTION CRITERIA: All randomised controlled trials of adult
      individual outpatient therapy for anorexia nervosa as defined by the DSM-IV or
      similar international criterion. Quality ratings were made according to the CCDAN
      criteria and in addition, whether the trial had examined treatment integrity.
      DATA COLLECTION AND ANALYSIS: A range of outcome variables were selected,
      including physical state, severity of eating disorder attitudes and beliefs,
      interpersonal function, and general psychiatric symptom severity. Continuous
      outcome data comparisons were made with the standardized mean difference
      statistic, and binary outcome comparisons made with the relative risk statistic.
      Reliability of data extraction and quality ratings were made with the kappa
      statistic. Sensitivity analyses to evaluate the effects of trial quality and
      subgroup analyses to explore specific questions of treatment effects from
      different settings, frequency and duration of therapies were planned. MAIN
      RESULTS: Six small trials only, two of which included children or adolescents,
      were identified from the search and aggregation of data was not possible. Bias
      was possible due particularly to lack of blinding of outcome assessments. The
      results in two trials suggested that 'treatment as usual' or similar may be less
      efficacious than a specific psychotherapy. No specific treatment was consistently
      superior to any other specific approach. Dietary advice as a control arm had a
      100% non-completion rate in one trial. REVIEWER'S CONCLUSIONS: No specific
      approach can be recommended from this review. It is unclear why 'treatment as
      usual' performed so poorly or why dietary advice alone appeared so unacceptable
      as the reasons for non-completion were not reported. There is an urgent need for
      large well-designed trials in his area.

PMID- 14583999
TI  - Orientation and mobility training for adults with low vision.
AB  - BACKGROUND: Orientation and mobility (O&M) training is provided to people who are
      visually impaired to help them maintain travel independence, teaching them new
      orientation and mobility skills to compensate for reduced visual information.
      OBJECTIVES: The objective of this review was to assess the effects of orientation
      and mobility training, with or without associated devices, for adults with low
      vision. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled
      Trials - CENTRAL (which contains the Cochrane Eyes and Vision Group trials
      register) (Issue 3 2002), MEDLINE (1966 to August 2002), EMBASE (1980 to
      September 2002) and LILACS (September 2002) and the reference lists of articles.
      SELECTION CRITERIA: We planned to include randomised or quasi-randomised trials
      comparing orientation and mobility training with no training in adults with low
      vision. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the
      search results for eligibility. MAIN RESULTS: No studies were found that
      satisfied the inclusion criteria. REVIEWER'S CONCLUSIONS: We could not find any
      controlled trials on the effects of orientation and mobility training for adults
      with low vision. As a premise to future trials, orientation and mobility
      instructors and scientists should reach a consensus and develop valid measures of
      mobility performance which are both reliable and meaningful to people with low
      vision.

PMID- 14584000
TI  - Granulocyte transfusions for neonates with confirmed or suspected sepsis and
      neutropaenia.
AB  - BACKGROUND: Neonatal sepsis causes significant neonatal mortality and morbidity.
      Neonates, especially preterm infants, have an immaturity of granulopoeisis and
      have a limited capacity for progenitor cell proliferation. This results in the
      frequent occurrence of neutropaenia in septic neonates. Neutropaenic septic
      neonates have a higher mortality than neonates who are septic but not
      neutropaenic. Transfusion of granulocytes to septic neutropaenic neonates,
      therefore, may help reduce mortality and morbidity. OBJECTIVES: The primary
      objective of this review was to determine the efficacy and safety of granulocyte
      preparations (granulocyte and buffy coat transfusions) as adjuncts to antibiotics
      for the treatment of confirmed or suspected sepsis in neonates with neutropaenia
      in reducing all-cause mortality during hospital stay and adverse neurological
      outcome at a year of age or later. Secondary objectives were to determine the
      effects of granulocyte transfusions on length of hospital stay in survivors to
      discharge, adverse effects (fluid overload, transmission of blood borne
      infections, pulmonary complications and sensitisation to donor leukocyte
      antigens) and immunologic outcomes at a year of age or later. SEARCH STRATEGY:
      Searches for eligible trials were made in September 2002 of the following
      electronic databases: The Cochrane Central Register of Controlled Trials
      (CENTRAL, The Cochrane Library, Issue 3, 2002), MEDLINE, EMBASE, CINAHL. The
      proceedings of the Pediatric Academic Societies, which were published in the
      journal, Pediatric Research, were searched from 1987 onwards. The Cambridge
      Database of Scientific Abstracts (1982 onwards) and Dissertation Abstracts on
      disc (1960 onwards) were also searched. Communications with prominent authors in
      the field and additional searches in the reference lists of identified trials
      were performed SELECTION CRITERIA: Randomised and quasi-randomised studies were
      included, if the participants were neonates with suspected or confirmed sepsis
      and neutropaenia who received granulocyte preparations (granulocyte concentrates
      prepared by leukophoresis or buffy coat transfusions prepared by simple
      centrifugation of blood) at any dose or duration compared with placebo or no
      granulocyte transfusion, each as adjuncts to antibiotics or compared to other
      adjuncts to antibiotics to treat sepsis (e.g. intravenous immunoglobulin).
      Studies were included if any of the following outcomes were reported: all-cause
      mortality during hospital stay, neurological outcome at one year of age or later,
      length of hospital stay in survivors at discharge, adverse effects or
      immunological outcome at one year or later DATA COLLECTION AND ANALYSIS: Trials
      identified by the search strategy were assessed for eligibility for inclusion in
      the review. Full text versions of the eligible trials were obtained. Data of
      interest were extracted on paper forms. Relative risk (RR) and risk difference
      (RD) with 95% confidence intervals using the fixed effects model were reported
      for dichotomous outcomes. Pre-specified subgroup analyses were done and reported.
      MAIN RESULTS: Four eligible studies were identified. A total of 44 infants with
      sepsis and neutropaenia on antibiotics were randomised in three trials to
      granulocyte transfusions OR placebo/no transfusion. In another trial, 35 infants
      with sepsis and neutropaenia on antibiotics were randomised to granulocyte
      transfusion or intravenous immunoglobulin. When granulocyte transfusions were
      compared with placebo or no transfusion, there was no significant difference in
      all-cause mortality [typical RR 0.89 (95% CI 0.43, 1.86), typical RD -0.05 (95%
      CI -0.31, 0.21)]. There was no statistical heterogeneity in the results of the
      included trials. When granulocyte transfusions were compared with intravenous
      immunoglobulin, there was a reduction in all-cause mortality of borderline
      statistical significance [RR 0.06 (95% CI 0.00, 1.04), RD -0.34(95% CI -0.60, 
      0.09), NNT 2.9 (95% CI 1.7, 11.1)]. Pulmonary complication, seen in four infants
      (4%), was the only adverse effect reported. This adverse effect was noticed in
      the two trials which used buffy coat transfusions. None of the trials reported on
      neurological outcome at one year of age or later, length of hospital stay in
      survivors to discharge or immunological outcome at one year of age or later.
      REVIEWER'S CONCLUSIONS: Currently, there is inconclusive evidence from RCTs to
      support or refute the routine use of granulocyte transfusions in neonates with
      sepsis and neutropaenia to reduce mortality and morbidity. Researchers can be
      encouraged to conduct adequately powered multicentre trials of granulocyte
      transfusions to clarify their role in neonates with sepsis and neutropaenia.
      Other adjuncts to antibiotics aimed at improving host defence mechanisms such as
      colony stimulating factors, IVIG and pentoxifylline should also be tested in
      RCTs.

PMID- 14584001
TI  - Immunosuppressive agents for treating IgA nephropathy.
AB  - BACKGROUND: IgA nephropathy (IgAN) is a world-wide disease and the cause of end
      stage renal failure (ESRF) in 15 to 20% of patients within 10 years and in 30 to
      40% of individuals within 20 years from the apparent onset of disease. No
      specific treatment has yet been established but many approaches have been
      investigated. OBJECTIVES: To assess the benefits and harms of immunosuppressive
      treatment for IgAN. SEARCH STRATEGY: We searched The Cochrane Renal Group's
      specialized register (May 2003), Cochrane Central Register of Controlled Trials
      (CENTRAL) (The Cochrane Library, Issue 3, 2002) MEDLINE (1966 - September 2002),
      EMBASE (1988 - September 2002) and handsearched reference lists of retrieved
      articles and conference proceedings. SELECTION CRITERIA: Randomized controlled
      trials (RCTs) and quasi-RCTs comparing treatment of IgAN with immunosuppressive
      agents against placebo, no treatment, other immunosuppressive or non
      immunosuppressive agents. DATA COLLECTION AND ANALYSIS: Two reviewers
      independently assessed trial quality and extracted data. Statistical analyses
      were performed using the random effects model and the results expressed as
      relative risk (RR) for dichotomous outcomes and weighted mean difference (WMD)
      for continuous outcomes, with 95% confidence intervals (CI). MAIN RESULTS:
      Thirteen eligible RCTs involving 623 patients were identified. All identified
      RCTs had a placebo, no treatment or warfarin/dipyridamole control group. Seven
      trials used steroids, three used alkylating agents/cyclosporin and three used
      combinations of steroids and alkylating agents/cyclosporin. No trial directly
      compared steroids versus alkylating agents/cyclosporin. Quality was sub-optimal.
      Steroids were associated with a lower risk of progression to ESRF (RR 0.44, 95%
      CI 0.25 to 0.80) and lower urinary protein excretion (WMD -0.49 g/24h, 95% CI 
      0.72 to -0.12). Urinary protein excretion was lower for patients treated with
      alkylating agents/cyclosporin compared to placebo/no treatment (WMD -0.94 g/24h,
      95% CI -1.43 to -0.46). There was no significant reduction of urinary protein
      excretion with combination treatment of steroids and alkylating agents compared
      with placebo/no treatment. REVIEWER'S CONCLUSIONS: The optimal management of IgAN
      remains uncertain. The RCTs identified were small, of sub-optimal methodological
      quality and tended to only report favorable and surrogate outcomes without a
      thorough reporting of treatment harms. All outcomes favor the use of
      immunosuppressive interventions, with steroids appearing to be the most
      promising. Further study, in the form of RCTs, is necessary to ascertain which
      patients would benefit from these interventions, whether they are the ones with
      early signs of renal dysfunction or those with more advanced renal impairment.

PMID- 14584002
TI  - Intravenous immunoglobulin for the treatment of Kawasaki disease in children.
AB  - BACKGROUND: Kawasaki disease is the most common cause of acquired heart disease
      in children in developed countries. The coronary arteries supplying the heart can
      be damaged in Kawasaki disease. The principal advantage of timely diagnosis is
      the potential to prevent this complication with early treatment. Intravenous
      immunoglobulin (IVIG) is widely used for this purpose. OBJECTIVES: The objective
      of this review was to evaluate the effectiveness of IVIG in treating, and
      preventing cardiac consequences, of Kawasaki disease in children. SEARCH
      STRATEGY: Electronic searches of the Cochrane Peripheral Vascular Disease Group
      Specialised Register, CENTRAL, MEDLINE, EMBASE, and CINAHL were performed (last
      searched April 2003). We also searched references from relevant articles and
      contacted authors where necessary. In addition we contacted experts in the field
      for unpublished works. SELECTION CRITERIA: Randomised controlled trials of
      intravenous immunoglobulin to treat Kawasaki disease were eligible for inclusion.
      DATA COLLECTION AND ANALYSIS: Fifty-nine trials were identified in the initial
      search. On careful inspection only sixteen of these met all the inclusion
      criteria. Trials were data extracted and assessed for quality by at least two
      reviewers. Data were combined for meta-analysis using relative risk ratios for
      dichotomous data or weighted mean difference for continuous data. A random
      effects statistical model was used. MAIN RESULTS: The meta-analysis of IVIG
      versus placebo, including all children, showed a significant decrease in new
      coronary artery abnormalities (CAAs) in favour of IVIG, at thirty days RR (95%
      CI) = 0.74 (0.61 to 0.90). No statistically significant difference was found
      thereafter. A subgroup analysis excluding children with CAAs at enrollment also
      found a significant reduction of new CAAs in children receiving IVIG RR (95%) =
      0.67 (0.46 to 1.00). There was a trend towards benefit from IVIG at sixty days
      (p=0.06). Results of dose comparisons showed a decrease in the number of new CAAs
      with increased dose. The meta-analysis of 400 mg/kg/day for five days versus 2
      gm/kg in a single dose showed statistically significant reduction in CAAs at
      thirty days RR (95%) = 4.47 (1.55 to 12.86). This comparison also showed a
      significant reduction in duration of fever with the higher dose. There was no
      statistically significant difference noted between different preparations of
      IVIG. There was no statistically significant difference of adverse effects in any
      group. REVIEWER'S CONCLUSIONS: Children fulfilling the diagnostic criteria for
      Kawasaki disease should be treated with IVIG (2 gm/kg single dose) within 10 days
      of onset of symptoms.

PMID- 14584003
TI  - H. pylori eradication therapy vs. antisecretory non-eradication therapy (with or
      without long-term maintenance antisecretory therapy) for the prevention of
      recurrent bleeding from peptic ulcer.
AB  - BACKGROUND: Peptic ulcer is the main cause for upper gastrointestinal
      haemorrhage, and Helicobacter pylori infection is the main etiologic factor for
      peptic ulcer disease. Maintenance antisecretory therapy has been the standard
      long-term treatment for patients with bleeding ulcers to prevent recurrent
      bleeding. On the other hand, the precise efficacy of H. pylori eradication for
      the prevention of rebleeding from peptic ulcer is unknown. OBJECTIVES: To compare
      the efficacy of H. pylori eradication therapy vs. antisecretory non-eradication
      therapy (with or without long-term maintenance antisecretory therapy) for the
      prevention of recurrent bleeding from peptic ulcer. SEARCH STRATEGY: We searched
      the Cochrane Controlled Trials Register (the Cochrane Library issue 1, 2003),
      MEDLINE (January 1966 to March 2003), EMBASE (January 1988 to March 2003), CINAHL
      (January 1982 to March 2003), and reference lists of articles. We also conducted
      a manual search from several congresses. SELECTION CRITERIA: Controlled clinical
      trials comparing the efficacy of H. pylori eradication therapy vs. antisecretory
      non-eradication therapy (with or without long-term maintenance antisecretory
      therapy) for the prevention of recurrent bleeding from peptic ulcer. DATA
      COLLECTION AND ANALYSIS: Extraction and quality assessment of studies were done
      by two reviewers. Study authors were contacted for additional information. MAIN
      RESULTS: Six studies with a total of 355 patients were included in the first meta
      analysis: mean percentage of rebleeding in H. pylori eradication therapy group
      was 4.5%, and in the non-eradication therapy group without subsequent long-term
      maintenance antisecretory therapy it was 23.7% (OR 0.18, 95% CI 0.09 to 0.37;
      there was no statistical evidence of heterogeneity; NNT was 5, 95% CI 4 to 8).
      Three studies with a total of 470 patients were included in the second meta
      analysis: mean percentage of rebleeding in H. pylori eradication therapy group
      was 1.6%, and in non-eradication therapy group with long-term maintenance
      antisecretory therapy it was 5.6% (OR 0.25, 95% CI 0.08 to 0.76; heterogeneity
      was not demonstrated; NNT was 20, 95% CI 12 to 100). Subanalysis. Excluding
      patients taking non-steroidal anti-inflammatory drugs (NSAIDs) at the time of
      recurrent bleeding resulted in a rebleeding rate of 4% (first meta-analysis) or
      0.78% (second meta-analysis) in the group receiving H. pylori eradication
      therapy. When only patients with H. pylori eradication success were included,
      rebleeding rate was 1% in H. pylori eradication therapy group, and NNT decreased
      from 5 to 4. In some cases, recurrence of H. pylori infection seemed to be
      responsible for recurrence of bleeding. REVIEWER'S CONCLUSIONS: Treatment of H.
      pylori infection is more effective than antisecretory non-eradicating therapy
      (with or without long-term maintenance antisecretory therapy) in preventing
      recurrent bleeding from peptic ulcer. Consequently, all patients with peptic
      ulcer bleeding should be tested for H. pylori infection, and eradication therapy
      should be prescribed to H. pylori-positive patients.

PMID- 14584004
TI  - Long-term pharmacotherapy for obesity and overweight.
AB  - BACKGROUND: Worldwide prevalence rates of obesity and overweight are rising and
      safe and effective treatment strategies are urgently needed. A number of anti
      obesity agents have been studied in short-term clinical trials, but long-term
      efficacy and safety need to be established. OBJECTIVES: To assess/compare the
      effects and safety of approved anti-obesity medications in clinical trials of at
      least one-year duration. SEARCH STRATEGY: MEDLINE, EMBASE, the Cochrane
      Controlled Trials Register, the Current Science Meta-register of Controlled
      Trials, and reference lists of original studies and reviews were searched. Date
      of last search was December 2002. Drug manufacturers and two obesity experts were
      contacted in to detect unpublished trials. No language restrictions were imposed.
      SELECTION CRITERIA: Double-blind, randomised controlled weight loss and weight
      maintenance trials of approved anti-obesity agents that 1) enrolled adult
      overweight or obese patients, 2) included a placebo control group or compared two
      or more anti-obesity drugs 3) used an intention-to-treat analysis, and 4) had a
      minimum follow-up period of one year. Abstracts and pseudo-randomised trials were
      not included. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed
      all potentially relevant citations for inclusion and methodological quality. The
      primary outcome measure was weight loss. MAIN RESULTS: Of the eight anti-obesity
      agents investigated, only orlistat and sibutramine trials met inclusion criteria.
      Eleven orlistat weight loss studies (four of which reported a second year weight
      maintenance phase) and five sibutramine studies (three weight loss and two weight
      maintenance trials) were included. Attrition rates averaged 33% during the weight
      loss phase of orlistat trials and 43% in sibutramine studies. All patients
      received lifestyle modification as a co-intervention. Compared to placebo,
      orlistat-treated patients lost 2.7 kg (95% CI: 2.3 kg to 3.1 kg) or 2.9% (95% CI:
      2.3 % to 3.4%) more weight and patients on sibutramine experienced 4.3 kg (95%
      CI: 3.6 kg to 4.9 kg) or 4.6% (95% CI: 3.8% to 5.4%) greater weight loss. The
      number of patients achieving ten percent or greater weight loss was 12% (95% CI:
      8% to 16%) higher with orlistat and 15% (95% CI: 4% to 27%) higher with
      sibutramine therapy. Weight loss maintenance results were similar. Orlistat
      caused gastrointestinal side effects and sibutramine was associated with small
      increases in blood pressure and pulse rate. REVIEWER'S CONCLUSIONS: Studies
      evaluating the long-term efficacy of anti-obesity agents are limited to orlistat
      and sibutramine. Both drugs appear modestly effective in promoting weight loss;
      however, interpretation is limited by high attrition rates. Longer and more
      methodologically rigorous studies of anti-obesity drugs that are powered to
      examine endpoints such as mortality and cardiovascular morbidity are required to
      fully evaluate any potential benefit of such agents.

PMID- 14584005
TI  - Noninvasive positive pressure ventilation as a weaning strategy for intubated
      adults with respiratory failure.
AB  - BACKGROUND: Noninvasive positive pressure ventilation (NPPV) provides ventilatory
      support without the need for an invasive airway. Interest has emerged in using
      NPPV to facilitate earlier removal of the endotracheal tube and decrease
      complications associated with prolonged intubation. OBJECTIVES: To summarize the
      evidence comparing NPPV and invasive positive pressure ventilation (IPPV) weaning
      on clinical outcomes in intubated adults with respiratory failure. SEARCH
      STRATEGY: We searched the Cochrane Central Register of Controlled Trials (The
      Cochrane Library, issue 2, 2003), MEDLINE (January 1966 to July 2003) and EMBASE
      (January 1980 to July 2003) for randomized controlled trials comparing NPPV and
      IPPV weaning. Additional data sources included personal files, conference
      proceedings and author contact. SELECTION CRITERIA: Randomized and quasi
      randomized studies comparing early extubation with immediate application of NPPV
      to IPPV weaning in intubated adults with respiratory failure. DATA COLLECTION AND
      ANALYSIS: Two reviewers independently assessed trial quality and abstracted data
      according to prespecified criteria. Sensitivity and subgroup analyses were
      planned to assess the impact of (i) excluding quasi-randomized trials and (ii)
      the etiology of respiratory failure on outcomes. MAIN RESULTS: We identified
      eleven trials, of which five were included, involving 171 participants with
      predominantly chronic obstructive pulmonary disease. Overall, the included
      studies were of moderate to good quality. Compared to the IPPV strategy, the NPPV
      strategy decreased mortality (RR 0.41, 95% CI 0.22 to 0.76), the incidence of
      ventilator associated pneumonia (RR 0.28, 95% CI 0.09 to 0.85), intensive care
      unit length of stay (WMD -6.88 days, 95% CI -12.60 to -1.15), hospital length of
      stay (WMD -7.33 days, 95%CI -14.05 to -0.61), total duration of mechanical
      support (WMD -7.33 days, 95% CI -11.45 to -3.22) and the duration of endotracheal
      mechanical ventilation (WMD -6.79 days, 95% CI -11.70 to -1.87). There was no
      effect of NPPV on weaning failures or the duration of mechanical support related
      to weaning and insufficient data to pool adverse events or quality of life.
      Excluding a single quasi-randomized trial maintained the significant reduction in
      mortality and ventilator associated pneumonia. Subgroup analyses suggested that
      the mortality benefit of the NPPV approach is greater in patients with chronic
      obstructive pulmonary disease. REVIEWER'S CONCLUSIONS: Summary estimates from
      five studies of moderate to good quality demonstrated a consistent positive
      effect on overall mortality. At present, use of NPPV to facilitate weaning in
      mechanically ventilated patients, with predominantly chronic obstructive lung
      disease, is associated with promising, although insufficient, evidence of net
      clinical benefit.

PMID- 14584006
TI  - Screening programmes for the early detection and prevention of oral cancer.
AB  - BACKGROUND: Although the second half of the last century has generated a rich and
      complex body of knowledge, the burden of oral cancer is still largely present. As
      with other cancers, there has been a strong debate whether screening strategies
      for oral cancer such as visual examination, the use of toluidine blue or newer
      methods such as brush biopsy or fluorescence imaging are effective in reducing
      the mortality rate associated with oral cancer. OBJECTIVES: To assess the
      effectiveness of current screening methods in decreasing oral cancer mortality.
      SEARCH STRATEGY: Electronic databases (MEDLINE, CANCERLIT, EMBASE, the Cochrane
      Central Register of Controlled Trials; 1966 to September 2002, The Cochrane
      Library - Issue 2, 2002), bibliographies, handsearching of specific journals and
      contact authors were used to identify published and unpublished data. SELECTION
      CRITERIA: Randomised controlled trials of screening for oral cancer or
      potentially premalignant oral lesions using visual examination, toluidine blue,
      fluorescence imaging or brush biopsy. DATA COLLECTION AND ANALYSIS: The search
      found 100 citations and these have been reviewed. One randomised controlled trial
      of screening strategies for oral cancer was identified as meeting the review's
      inclusion criteria. Validity assessment, data extraction and statistics
      evaluation have been undertaken by two independent reviewers. MAIN RESULTS: One
      ongoing randomised controlled trial has been included (n = 13 clusters: 153,708
      eligible subjects, 130,799 included subjects). There was no difference in the age
      standardised oral cancer mortality rates for the screened group (21.2/1000,000
      person years) and the control group (21.3/100,000 person years). However this
      study has some methodological weaknesses. REVIEWER'S CONCLUSIONS: Given the
      limitation of evidence (only one included randomised controlled trial) and the
      potential methodological weakness in the included study, it is valid to say that
      there is no evidence to support or refute the use of a visual examination as a
      method of screening for oral cancer using a visual examination in the general
      population. Furthermore, no robust evidence exists to suggest other methods of
      screening, toluidine blue, fluorescence imaging or brush biopsy, are either
      beneficial or harmful. Further cost-effective, high quality studies to assess the
      efficacy and effectiveness of screening are required. In addition, studies to
      elucidate the natural history of oral cancer, prevention methods and the
      effectiveness of opportunistic screening in high risk groups are needed.

PMID- 14584007
TI  - Depot risperidone for schizophrenia.
AB  - BACKGROUND: Risperidone is the first new generation antipsychotic drug made
      available in a long acting injection. OBJECTIVES: To examine the clinical effects
      of depot risperidone for people with schizophrenia and schizophrenia-like
      psychoses. SEARCH STRATEGY: We searched the Cochrane Schizophrenia Group's
      Register (December 2002), references of all included studies, and contacted
      industry and authors of included studies. SELECTION CRITERIA: Randomised clinical
      trials comparing depot risperidone with other treatments for people with
      schizophrenia and/or schizophrenia-like psychoses. DATA COLLECTION AND ANALYSIS:
      Two reviewers independently inspected citations and/or abstracts, ordered papers,
      re-inspected and quality assessed the results, and extracted data. For
      dichotomous data, we calculated the relative risk (RR), the 95% confidence
      interval (CI) and, where appropriate, the number needed to treat (NNT), on an
      intention-to-treat basis. For continuous data, we calculated weighted mean
      differences (WMD). MAIN RESULTS: One study (n=400) compared depot risperidone
      with placebo but 56% of people did not complete the three-month study rendering
      most global and mental state data unusable. Risperidone depot compared with
      placebo did not affect levels of anxiety (n=400, RR 0.58 CI 0.32 to 1.05) but may
      decrease agitation (n=400, RR 0.60 CI 0.39 to 0.92). Risperidone depot did not
      substantially influence hallucinations (n=400, RR 1.23 CI 0.47 to 3.22) but
      'psychosis' was reduced (n=400, RR 0.52 CI 0.33 to 0.83, NNT 9 CI 7 to 26).
      Attrition was higher for the placebo group compared with people allocated
      risperidone depot (n=400, RR 0.74 CI 0.63 to 0.88, NNT 6 CI 4 to 12). Severe
      adverse events were common (13% to 23%) but significantly more so in the placebo
      group (n=400, RR 0.59 CI 0.38 to 0.93, NNT 11 CI 7 to 70). Poor reporting,
      however, makes these difficult to interpret. Movement disorders were equally
      common in both groups (n=400, RR 2.38 CI 0.73 to 7.78) although it looks as if
      there is a trend for the higher depot doses to encourage movement disorders. One
      study (n=640) compared depot risperidone against oral risperidone for stable
      people with relatively mild illness. For global outcomes there was no clear
      difference between the depot group and oral group (n=640, RR 'no global
      improvement' 1.06 CI 0.92 to 1.22). Mental state measures were also similar
      across groups. Overall, in this study compliance was good (n=640, RR <4
      injections or "major protocol violation" 1.16 CI 0.81 to 1.67). Adverse effects
      were poorly reported but over half of both groups reported some adverse effect
      (n=640, RR 1.04 CI 0.91 to 1.18). REVIEWER'S CONCLUSIONS: There is no reliable
      data to support the claim that depot risperidone is beneficial for people with
      schizophrenia. For reasonably well, stable people it may mean that the need for
      regular oral doses can be avoided, but adverse affects are not well reported. For
      more severely ill people, few benefits are evident although it may increase
      compliance with injections in comparison with placebo. Use of depot risperidone,
      especially at the higher doses, is weakly associated with movement disorders.
      Well designed and reported, randomised studies, firmly grounded in real world
      clinical practice are needed to fully assess the effects of this new preparation.

PMID- 14584008
TI  - Compression therapy for treating stage I and II (Widmer) post-thrombotic
      syndrome.
AB  - BACKGROUND: Post-thrombotic syndrome (PTS) is a long-term complication of deep
      vein thrombosis characterised by chronic complaints, swelling, and skin changes
      in the affected limb. One in every three patients with deep vein thrombosis
      develops post-thrombotic complications within five years. OBJECTIVES: To assess
      the effectiveness of compression therapy in patients with stage I and II post
      thrombotic syndrome according to the classification of Widmer. Interventions of
      interest included elastic compression stockings and mechanical devices, compared
      with no intervention and with each other. SEARCH STRATEGY: The reviewers searched
      the Cochrane Peripheral Vascular Diseases Specialised Trials Register (last
      searched April 2003), and the Cochrane Central Register of Controlled Trials
      (CENTRAL) (last searched Issue 1, 2003). In addition, journals, conference
      proceedings and bibliographies were hand searched. Personal contact with other
      investigators involved in the clinical area was sought to get information about
      missed or unpublished studies. SELECTION CRITERIA: Trials that evaluated
      compression therapy for stage I and II (Widmer) post-thrombotic syndrome. Primary
      outcomes were leg ulceration, or deterioration of post-thrombotic syndrome. There
      were no restrictions on date or language. One reviewer (DNK) assessed titles and
      abstracts for relevance. This was verified independently by a second reviewer
      (MWCS). DATA COLLECTION AND ANALYSIS: Details of eligible studies were extracted
      and summarised using data extraction sheets. Data extraction was undertaken by
      one reviewer (DNK) and verified by a second reviewer (MHP). MAIN RESULTS: Only
      two trials were identified that addressed physical treatment of post-thrombotic
      syndrome. Both trials were initiated by the same group of investigators. A cross
      over study lasting two months compared low and high pressure with intermittent
      compression units for severe post-thrombotic syndrome. This showed a beneficial
      effect of higher pressures. The second study, in patients with mild to moderate
      post-thrombotic symptoms, showed no effect of elastic compression stockings (30
      40 mm Hg at the ankle region) when compared to 'placebo' stockings that were one
      to two sizes too large. REVIEWER'S CONCLUSIONS: There is some evidence of a
      beneficial effect of intermittent pneumatic compression units, but the study was
      too small and of too short a duration to draw strong conclusions. Further
      research is needed in order to assess whether intermittent pneumatic compression
      units give long term reduction and relief of the symptoms caused by post
      thrombotic syndrome, and prevent deterioration and leg ulceration. The use of
      elastic compression stockings to treat post-thrombotic syndrome cannot be
      supported on the basis of the currently available data.

PMID- 14584009
TI  - Pentoxifylline for neonatal sepsis.
AB  - BACKGROUND: Although the overall incidence of neonatal sepsis has declined over
      the past decade, mortality remains high in the pre term infant. The high level of
      mortality and morbidity from sepsis despite the use of potent anti-microbial
      agents, and the global emergence of antibiotic resistance, have led to the search
      for new modalities to boost new born host defences. Pentoxifylline, a xanthine
      derivative and a phosphodiesterase inhibitor, has been shown to possess a broad
      spectrum of activity modulating inflammation. OBJECTIVES: The primary objective
      was to assess the effect on mortality and the safety of intravenous
      pentoxifylline as an adjunct to antibiotic therapy in neonates with suspected or
      confirmed sepsis. SEARCH STRATEGY: The Cochrane Central Register of Controlled
      Trials (CENTRAL, The Cochrane Library, Issue 4, 2002), MEDLINE, EMBASE and CINAHL
      were searched in October 2002 and again in March 2003. Science Citation Index for
      articles referencing Lauterbach 1996 and Lauterbach 1999 was searched as well as
      proceedings of the Pediatric Academic Societies which were published in Pediatric
      Research from 1980. Doctoral dissertations and theses were searched from 1980.
      The reference lists of identified RCTs, and personal files were searched. No
      language restriction was applied. SELECTION CRITERIA: Studies were included if
      they were randomised or quasi-randomised trials, assessing the efficacy of
      pentoxifylline compared to placebo or no intervention as an adjunct to antibiotic
      therapy of suspected or confirmed sepsis in newborn infants less than 28 days
      old. Eligible trials were required to report treatment effects on at least one of
      the following outcomes: all cause mortality during initial hospital stay,
      neurological development at two years of age or later, length of hospital stay,
      duration of ventilation via endotracheal intubation, chronic lung disease in
      survivors, periventricular leukomalacia, necrotising enterocolitis, or adverse
      events. DATA COLLECTION AND ANALYSIS: Two reviewers independently abstracted
      information for the outcomes of interest. Any differences were resolved by mutual
      discussion. Typical Relative Risk (RR) and Risk Difference (RD) with 95%
      confidence intervals (CI) using fixed effects model are reported for dichotomous
      outcomes. NNT was calculated for outcomes for which there was a statistically
      significant reduction in RD. MAIN RESULTS: Two RCTs enrolled a total of 140
      preterm (< 36 weeks) neonates with suspected late onset (> 7 days) sepsis to
      evaluate the effect of pentoxifylline on neonatal outcomes. However, the two
      studies reported outcomes of only the 107 randomised patients with confirmed
      sepsis. The results showed a reduction in 'all cause mortality during hospital
      stay' following pentoxifylline treatment [typical RR 0.14 (95% CI 0.03, 0.76), RD
      -0.16 (95% CI -0.27, - 0.04), NNT 6 (95% CI 4, 25)]. No adverse effects due to
      pentoxifylline were observed in the two included trials. No other outcomes of
      interest were reported. REVIEWER'S CONCLUSIONS: Current evidence suggests that
      the use of pentoxifylline as an adjunct to antibiotics in neonatal sepsis reduces
      mortality without any adverse effects. But the number of neonates studied is
      small and considerable methodological weaknesses exist in the included trials.
      Hence these results should be interpreted with caution. Researchers are
      encouraged to undertake large well-designed trials to confirm or refute the
      effectiveness of pentoxifylline to reduce mortality and adverse outcomes in
      neonates with suspected or confirmed neonatal sepsis. Researchers might also
      compare pentoxifylline with other adjuncts to antibiotics which modulate
      inflammation (e.g. intravenous immunoglobulins, haematopoetic colony stimulating
      factors among others) in reducing mortality and morbidity due to neonatal sepsis.

PMID- 14584010
TI  - The effect of vitamin B6 on cognition.
AB  - BACKGROUND: Micronutrient status can affect cognitive function at all ages.
      Vitamin deficiencies could influence memory function and might contribute to age
      associated cognitive impairment and dementia. Vitamin B6, comprising three
      chemically distinct compounds pyridoxal, pyridoxamine, and pyridoxine, is
      involved in the regulation of mental function and mood. Vitamin B6 is also an
      essential homocysteine re-methylation cofactor, and deficiency is associated with
      increase in blood homocysteine levels. Homocysteine is a risk factor for
      cerebrovascular disease and may also have directly toxic effects on neurons of
      the central nervous system. Neuropsychiatric disorders including seizures,
      migraine, chronic pain and depression have been linked to vitamin B6 deficiency.
      Epidemiological studies indicate that poor vitamin B6 status is common among
      older people. Hyperhomocysteinaemia has been suggested as a cause or mechanism in
      the development Alzheimer's disease and other forms of dementia. Supplementation
      with B vitamins including vitamin B6 has been shown to reduce blood homocysteine
      levels. OBJECTIVES: To assess the efficacy of vitamin B6 supplementation in
      reducing the risk of developing cognitive impairment by older healthy people, or
      improving cognitive functioning of people with cognitive decline and dementia,
      whether or not vitamin B6 deficiency has been diagnosed. SEARCH STRATEGY: The
      Specialized Register of the Cochrane Dementia and Cognitive Improvement Group was
      searched on 20 May 2003 using the terms: vitamin B6, pyridoxine, pyridoxamine,
      pyridoxal. For relevant trials on healthy elderly people MEDLINE, EMBASE and
      CENTRAL were searched using the previously mentioned terms as well as the term
      cognit * SELECTION CRITERIA: All unconfounded, double-blind randomized controlled
      trials in which the intervention with vitamin B6 was compared with placebo for
      healthy older people or people with cognitive decline or dementia. The primary
      outcome of interest was the efficacy of vitamin B6 supplementation on cognitive
      function. DATA COLLECTION AND ANALYSIS: The two reviewers independently evaluated
      all studies identified as possibly meeting the criteria for inclusion. One
      reviewer independently extracted the data. Studies were rated for their overall
      quality. The weighted mean differences between treatment and placebo groups, with
      95% confidence intervals, were calculated for each outcome. Review Manager
      version 4.2 was used to analyse the variance. MAIN RESULTS: No trials of vitamin
      B6 involving people with cognitive impairment or dementia were found. The two
      trials included in the review (Bryan 2002; Deijen 1992) used a double-blind,
      randomized, placebo-controlled design and involved 109 healthy older people. One
      trial restricted enrolment to women and the other to men. Vitamin B6
      supplementation and healthy older women: Bryan 2002 enrolled 211 healthy women
      from various age groups into a 5-week study. The trial was of multifactorial
      design with folic acid, vitamin B12, vitamin B6 and placebo in its four arms.
      Twelve healthy women aged 65 to 92 years received 75 mg vitamin B6 orally per day
      and were compared with 21 healthy women who were allocated to placebo. No
      statistically significant benefits from vitamin B6 on mood or cognition were
      observed. Vitamin B6 supplementation and healthy older men: Deijen 1992 recruited
      76 healthy men aged 70 to 79 years. They were divided into 38 matched pairs, one
      member of each pair randomly allocated to 20 mg of vitamin B6 (pyridoxine
      hydrochloride) per day for 12 weeks the other to placebo. No statistically
      significant differences between treatment and placebo were found in their effects
      on cognition or mood. Effect of vitamin B6 supplementation on vitamin B6 status:
      Deijen 1992 reported that 20 mg of pyridoxine hydrochloride per day for 12 weeks
      increased blood vitamin B6 activity as assessed as by plasma pyridoxal-5'
      phosphate (WMD 238, 95%CI 211.58 to 264.42, P<0.00001) and erythrocyte enzyme
      asparate aminotransferase (WMD 0.43, 95%CI 0.30 to 0.56, P<0.00001). Effect of
      vitamin B6 supplementation on blood homocysteine concentration: Neither of the
      included trials measured homocysteine levels. Drop-outs: All participants
      allocated to vitamin B6 or placebo completed the trial protocol. Adverse Events:
      No adverse effects were reported. Effect of vitamin B6 on carer burden, care
      costs and institutionalization rate: We found no trials in which these outcomes
      were assessed. REVIEWER'S CONCLUSIONS: This review found no evidence for short
      term benefit from vitamin B6 in improving mood (depression, fatigue and tension
      symptoms) or cognitive functions. For the older people included in one of the two
      trials included in the review, oral vitamin B6 supplements improved biochemical
      indices of vitamin B6 status, but potential effects on blood homocysteine levels
      were not assessed in either study. This review found evidence that there is scope
      for increasing some biochemical indices of vitamin B6 status among older people.
      More randomized controlled trials are needed to explore possible benefits from
      vitamin B6 supplementation for healthy older people and those with cognitively
      impairment or dementia.

PMID- 14584011
TI  - Granulocyte colony stimulating factor (G-CSF) as an adjunct to antibiotics in the
      treatment of pneumonia in adults.
AB  - BACKGROUND: Granulocyte colony stimulating factor (G-CSF) is a naturally
      occurring cytokine that has been shown to increase neutrophil function and
      number. Exogenous administration of recombinant G-CSF (filgrastim, pegfilgrastim
      or lenograstim) has found extensive use in the treatment of febrile neutropaenia,
      but its role in the treatment of infection in non-neutropaenic hosts is less well
      defined. OBJECTIVES: We aimed to explore the role of G-CSF as an adjunct to
      antibiotics in the treatment of pneumonia in non-neutropaenic adults. SEARCH
      STRATEGY: A search was performed using the Cochrane Central Register of
      Controlled Trials (issue 1, 2003); MEDLINE (January 1966 to April 2003); EMBASE
      (1988 to 2003); online databases of clinical trials; contact with corresponding
      authors; and contact with the manufacturers and distributors of G-CSF and reviews
      of citations in publications identified by the above strategies. SELECTION
      CRITERIA: We considered randomised controlled trials (RCTs) which included
      hospitalised adult patients with either community acquired pneumonia or hospital
      acquired pneumonia. DATA COLLECTION AND ANALYSIS: Studies identified were
      reviewed independently by two reviewers with data abstracted onto standardized
      data collection forms. The primary outcome measure was 28 day mortality.
      Secondary outcome measures included other markers of mortality as well as markers
      of adverse events, including organ dysfunction. An assessment of methodological
      quality was made for each study. MAIN RESULTS: G-CSF use appeared to be safe with
      no increase in the incidence of total serious adverse events (pooled OR 0.91, 95%
      CI: 0.73, 1.14) or organ dysfunction. However, the use of G-CSF was not
      associated with improved 28 day mortality (pooled OR 0.99, 95% CI 0.77, 1.29).
      REVIEWER'S CONCLUSIONS: There is no current evidence supporting the routine use
      of G-CSF in the treatment of pneumonia. Studies in which G-CSF is administered
      prophylactically or earlier in therapy may be of interest.

PMID- 14584012
TI  - New generation antipsychotics for first episode schizophrenia.
AB  - BACKGROUND: The new generation antipsychotics are associated with a lower risk of
      adverse effects compared with drugs such as haloperidol. Many treatment
      guidelines recommend the use of new generation ('atypical') antipsychotic drugs
      for people with a first episode of schizophrenia. OBJECTIVES: To examine the
      effects of the new generation antipsychotics for people with a first episode of
      schizophrenia or schizophrenia-like psychoses. SEARCH STRATEGY: The reviewers
      searched the Cochrane Schizophrenia Group's register (March 2002) and the
      included and excluded studies tables of relevant Cochrane reviews, references of
      all relevant studies, contacted industry and authors of relevant studies to
      identify further trials. SELECTION CRITERIA: Randomised clinical trials comparing
      new generation antipsychotics (amisulpride, clozapine, olanzapine, quetiapine,
      risperidone, sulpiride, ziprasidone, zotepine) with conventional antipsychotics
      for people with a first episode of schizophrenia or schizophrenia-like psychoses.
      DATA COLLECTION AND ANALYSIS: Citations and, where possible, abstracts were
      independently inspected by three reviewers, papers ordered, re-inspected and
      quality assessed. We independently extracted data but excluded them if loss to
      follow up was greater than 50%. For homogeneous dichotomous data, we calculated
      the relative risk (RR), the 95% confidence interval (CI) and, where appropriate,
      the number needed to treat (NNT), on an intention-to-treat basis. For continuous
      data, reviewers calculated weighted mean differences (WMD). MAIN RESULTS: We
      include two short-term studies (total n=266), one of which was a report of a sub
      group of a larger study. One compared risperidone with an average of 6 mg/day
      haloperidol and the other olanzapine with an average of 11 mg/day haloperidol.
      Compared with olanzapine, significantly more people receiving haloperidol left
      the study early (n=83, 1 RCT, RR 0.43 CI 0.3 to 0.7, NNH 3 CI 2 to 8). This was
      not so for the risperidone versus haloperidol comparison (n=183, 1 RCT, RR=0.7 CI
      0.4 to 1.1). In terms of global effects, studies reported no differences between
      risperidone and haloperidol (n=183, RR not much improved 1.0 CI 0.6 to 1.5), and
      olanzapine and the same control (n=83, RR needing at least one dose of
      benzodiazepine 0.8 CI 0.5 to 1.1). More people allocated to olanzapine had
      clinically significant improvement in mental state compared with those given
      haloperidol (n=83, RR no 'clinically significant improvement' 0.45 CI 0.3 to 0.7,
      NNH 3 CI 2 to 6). In the risperidone study, however, no such difference was
      apparent (n=183, RR 'no clinically significant improvement in mental state' 0.85
      CI 0.6 to 1.2). Significantly more people given haloperidol (4-16mg) experienced
      at least one adverse event when compared with risperidone (4-16mg) (n=183, RR 0.9
      CI 0.8 to 0.98, NNH 8 CI 4 to 50). Use of anticholinergic medication for
      extrapyramidal adverse events was less prevalent for people allocated either
      olanzapine (n=83, RR 0.3 CI 0.2 to 0.7, NNH 4 CI 2 to 14) or risperidone (n=183,
      RR 0.7 CI 0.5 to 0.9, NNH 4 CI 3 to 9) compared with those given haloperidol.
      There are no data at all on outcomes such as compliance, cost, social and
      cognitive functioning, relapse, rehospitalisation, or quality of life. There are
      no medium to long-term data. Eight ongoing studies may provide more information.
      REVIEWER'S CONCLUSIONS: The results of this review are inconclusive. Whether the
      use of new generation antipsychotics really makes the treatment less off putting
      and enhances long-term compliance is unclear. Pragmatic, well-designed and
      reported long-term trials would be useful to answer this question.

PMID- 14584013
TI  - Preoperative fasting for adults to prevent perioperative complications.
AB  - BACKGROUND: Fasting before general anaesthesia aims to reduce the volume and
      acidity of stomach contents during surgery, thus reducing the risk of
      regurgitation/aspiration. Recent guidelines have recommended a shift in fasting
      policy from the standard 'nil by mouth from midnight' approach to more relaxed
      policies which permit a period of restricted fluid intake up to a few hours
      before surgery. The evidence underpinning these guidelines however, was scattered
      across a range of journals, in a variety of languages, used a variety of outcome
      measures and methodologies to evaluate fasting regimens that differed in duration
      and the type and volume of intake permitted during a restricted fasting period.
      Practice has been slow to change. OBJECTIVES: To systematically review the effect
      of different preoperative fasting regimens (duration, type and volume of
      permitted intake) on perioperative complications and patient wellbeing (including
      aspiration, regurgitation and related morbidity, thirst, hunger, pain, nausea,
      vomiting, anxiety) in different adult populations. SEARCH STRATEGY: Electronic
      databases, conference proceedings and reference lists from relevant articles were
      searched for studies of preoperative fasting in August 2003 and experts in the
      area were consulted. SELECTION CRITERIA: Randomised controlled trials which
      compared the effect on postoperative complications of different preoperative
      fasting regimens on adults were included. DATA COLLECTION AND ANALYSIS: Details
      of the eligible studies were independently extracted by two reviewers and where
      relevant information was unavailable from the text attempts were made to contact
      the authors. MAIN RESULTS: Thirty eight randomised controlled comparisons (made
      within 22 trials) were identified. Most were based on 'healthy' adult
      participants who were not considered to be at increased risk of regurgitation or
      aspiration during anaesthesia. Few trials reported the incidence of
      aspiration/regurgitation or related morbidity but relied on indirect measures of
      patient safety i.e. intra-operative gastric volume and pH. There was no evidence
      that the volume or pH of participants' gastric contents differed significantly
      depending on whether the groups were permitted a shortened preoperative fluid
      fast or continued a standard fast. Fluids evaluated included water, coffee, fruit
      juice, clear fluids and other drinks (e.g. isotonic drink, carbohydrate drink).
      Participants given a drink of water preoperatively were found to have a
      significantly lower volume of gastric contents than the groups that followed a
      standard fasting regimen. This difference was modest and clinically
      insignificant. There was no indication that the volume of fluid permitted during
      the preoperative period (i.e. low or high) resulted in a difference in outcomes
      from those participants that followed a standard fast. Few trials specifically
      investigated the preoperative fasting regimen for patient populations considered
      to be at increased risk during anaesthesia of regurgitation/aspiration and
      related morbidity. REVIEWER'S CONCLUSIONS: There was no evidence to suggest a
      shortened fluid fast results in an increased risk of aspiration, regurgitation or
      related morbidity compared with the standard 'nil by mouth from midnight' fasting
      policy. Permitting patients to drink water preoperatively resulted in
      significantly lower gastric volumes. Clinicians should be encouraged to appraise
      this evidence for themselves and when necessary adjust any remaining standard
      fasting policies (nil-by-mouth from midnight) for patients that are not
      considered 'at-risk' during anaesthesia.

PMID- 14584014
TI  - Oral appliances for obstructive sleep apnoea.
AB  - BACKGROUND: Obstructive sleep apnoea-hypopnoea is a syndrome characterised by
      recurrent episodes of partial or complete upper airway obstruction during sleep
      that are usually terminated by an arousal. Nasal continuous positive airway
      pressure is the primary treatment for obstructive sleep apnoea-hypopnoea, but
      many patients are unable or unwilling to comply with this treatment. Oral
      appliances are an alternative treatment for sleep apnoea. OBJECTIVES: The
      objective was to review the effects of oral appliance in the treatment of sleep
      apnoea in adults. SEARCH STRATEGY: We searched MEDLINE 1966-2003, and the
      Cochrane Airways Group Sleep Apnoea RCT Register. Searches were current as of
      July 2003. Reference lists of articles were also searched. SELECTION CRITERIA:
      Randomised trials comparing oral appliance with control or other treatments in
      adults with sleep apnoea. DATA COLLECTION AND ANALYSIS: Trial quality was
      assessed and two reviewers extracted data independently. Study authors were
      contacted for missing information. MAIN RESULTS: Twelve trials involving 509
      participants were included. All the studies had some methodological shortcomings.
      Oral appliances improved apnoea-hypopnoea index compared with inactive control (
      13.17 AHI [-18.53 to -7.80] parallel group data - four studies). Oral appliances
      reduced daytime sleepiness in two trials (WMD -1.77 [95%CI: -2.91 to -0.62]).
      Oral appliances were less effective than continuous positive pressure in reducing
      apnoea-hypopnoea index (WMD 13 [95% CI: 7.63, 18.36], parallel studies - two
      trials; WMD 6.75 [4.93, 8.57] cross-over studies - six trials). However, no
      significant difference was observed on symptom scores (3 trials). Nasal
      continuous positive pressure was more effective at improving minimum arterial
      oxygen saturation during sleep compared with oral appliance. In two small
      crossover studies, participants preferred oral appliance therapy to continuous
      positive airways pressure. REVIEWER'S CONCLUSIONS: There is some limited evidence
      suggesting that oral appliance improves subjective sleepiness and sleep
      disordered breathing compared with a control. Nasal continuous positive airways
      pressure appears to be more effective in improving sleep disordered breathing
      than oral appliance. Until there is more definitive evidence on the effectiveness
      of oral appliances, it would appear to be appropriate to restrict oral appliance
      therapy to patients with sleep apnoea who are unwilling or unable to comply with
      continuous positive airways pressure therapy.

PMID- 14584015
TI  - Recombinant growth hormone for idiopathic short stature in children and
      adolescents.
AB  - BACKGROUND: Idiopathic short stature (ISS) refers to children who are very short
      compared with their peers for unknown or hereditary reasons. Recombinant human
      growth hormone has been used to increase growth and final height in children with
      idiopathic short stature. OBJECTIVES: To assess the effects of recombinant human
      growth hormone on short-term growth and final height in children with idiopathic
      short stature. SEARCH STRATEGY: Randomised controlled trials (RCTs) were sought
      by searching The Cochrane Central Register of Controlled Trials (CENTRAL),
      Medline, Embase, PubMed, Science Citation Index, BIOSIS and Current Controlled
      Trials (date of last search 10 December 2002). Article reference lists were
      assessed for trials and experts and pharmaceutical companies were contacted.
      SELECTION CRITERIA: Randomised controlled trials were included if they were
      carried out in children with ISS with normal growth hormone secretion. Growth
      hormone (GH) had to be administered for a minimum of six months and be compared
      with placebo or no treatment. A growth or height outcome measure had to be
      assessed. DATA COLLECTION AND ANALYSIS: Two reviewers assessed studies for
      inclusion criteria and for methodological quality. Data were extracted by one
      reviewer and checked by a second. The primary outcome was final height and
      secondary outcomes included short term growth, health related quality of life and
      adverse effects. To estimate summary treatment effects, data were pooled, when
      appropriate using a random effects model. MAIN RESULTS: Nine randomised
      controlled trials were included. One trial reported near final height in girls
      and found that girls treated with growth hormone were 7.5 cm taller than
      untreated controls (GH group, 155.3 cm +/- 6.4; control, 147.8 cm +/- 2.6; p =
      0.003). The other trials reported short term outcomes. Results suggest that short
      term height gains can range from none to approximately 0.7 SD over one year. One
      study reported health related quality of life and showed no significant
      improvement in growth hormone treated children compared with those in the control
      group. No serious adverse effects of treatment have been reported. REVIEWER'S
      CONCLUSIONS: Results suggest that growth hormone therapy can increase short-term
      growth and improve (near) final height. Increases in height are such that treated
      individuals remain relatively short when compared with peers of normal stature.
      Further research in the form of large, multicentre RCTs are required. These
      should focus on final height, which is the best outcome for assessing the effects
      of growth hormone, and address quality of life and cost issues.

PMID- 14584016
TI  - Naloxone for shock.
AB  - BACKGROUND: There is pre-clinical evidence, involving several animal species,
      suggesting that opioid peptides play a role in the physiopathology of shock
      (endotoxic, hypovolemic, cardiogenic, spinal, anaphylactic). Many case reports
      have suggested that naloxone (an opiate antagonist) might be an effective
      treatment for shock in humans, but others have not supported such a point of
      view. This controversy led us to undertake a meta-analysis of the available
      evidence on the efficacy of naloxone as a treatment measure of shock in humans.
      OBJECTIVES: To evaluate the effectiveness and safety of naloxone in human shock
      and to estimate the methodological quality of the clinical trials. SEARCH
      STRATEGY: Computerized bibliographic search up to December 2002, review of
      references of all papers found on the subject and contact with primary
      investigators of eligible studies. SELECTION CRITERIA: Randomized controlled
      trials evaluating naloxone in human shock, regardless of the patient's age
      (adult, child or neonate). DATA COLLECTION AND ANALYSIS: Three independent
      reviewers extracted data on study design, intervention, outcome and
      methodological quality. MAIN RESULTS: Three independent readers reviewed 80 human
      publications and selected six clinical trials. Overall agreement on study
      selection was perfect (concordance: 100%). This meta-analysis includes six
      studies involving 126 patients with septic, cardiogenic, hemorrhagic or spinal
      shock. Naloxone therapy was associated with statistically significant hemodynamic
      improvement (odds ratio 0.24; 95% confidence interval [95%CI] 0.09-0.68). The
      mean arterial pressure was significantly higher in the naloxone groups than in
      the placebo groups (weighted mean difference: +9.33 mmHg; 95%CI 7.07-11.59). No
      heterogeneity was found for this outcome. The death rate was lower in the
      naloxone group (odds ratio 0.59; 95%CI 0.21-1.67) but this was consistent with
      the play of chance. A significant heterogeneity for the latter outcome was
      detected (p<0.05). REVIEWER'S CONCLUSIONS: Naloxone improves blood pressure,
      especially mean arterial blood pressure. However, the clinical usefulness of
      naloxone to treat shock remains to be determined, and additional randomized
      controlled trials are needed to assess its usefulness.

PMID- 14584017
TI  - Interventions for improving communication with children and adolescents about a
      family member's cancer.
AB  - BACKGROUND: A diagnosis of cancer creates multiple problems for affected
      families, including major changes in living patterns, roles and relationships. It
      has not been common practice for families and health practitioners to share
      information with children or adolescents about a family member's cancer, or to
      allow them to express their feelings about this. In recent years, however,
      researchers and practitioners have begun to recognise that children and
      adolescents might appreciate and benefit by being better informed about, and
      having more opportunity to communicate their responses to, cancer in the family.
      OBJECTIVES: To examine the effects of different ways of enhancing communication
      with children and/or adolescents about a family member's cancer and its
      treatment. SEARCH STRATEGY: We searched the following sources: Cochrane Central
      Register of Controlled Trials (CENTRAL), The Cochrane Library, Issue 1 2003;
      MEDLINE (1966 to January week 2 2003); EMBASE (1985 to 2003 week 6); CINAHL (1982
      to February Week 1 2003); ERIC (1966 to 23 January 2003); PsycINFO (1985 to
      February week 1 2003). For the original (1999) version of this review we also
      searched the following databases: CancerLIT, Health Management Information
      Consortium, British Nursing Index, IAC Health & Wellness, JICSTE-Plus, Pascal,
      Linguistics and Language Behavior Abstracts, Mental Health Abstracts, AMED, HUMN,
      MANTIS and ASSIA. Bibliographies of identified studies were also checked and
      contact made with experts in the field. SELECTION CRITERIA: Randomised and non
      randomised controlled trials, and controlled and uncontrolled before and after
      studies that evaluated the effects of interventions to enhance communication with
      children and/or adolescents about a family member's cancer and its treatment.
      DATA COLLECTION AND ANALYSIS: Data on knowledge and understanding, coping,
      adjustment and wellbeing were extracted by one reviewer and checked by another
      reviewer. Study quality was assessed using six criteria. A qualitative synthesis
      of the results is presented. MAIN RESULTS: Five studies satisfied the selection
      criteria: one non-randomised controlled before and after study, and four
      uncontrolled before and after studies. They differed in terms of the
      interventions evaluated and the outcomes measured. One study of a camping program
      and two studies of structured group interventions reported improvements in cancer
      related knowledge. One out of two structured group intervention studies found
      significant reductions in psychological and social problems. The camping program
      study reported significant improvements in siblings' behaviour. One structured
      group intervention study reported significantly more positive mood states after
      the intervention. Another structured group intervention study reported
      significantly lower levels of anxiety after the intervention. REVIEWER'S
      CONCLUSIONS: Different methods of communicating with children and adolescents
      about a family member's cancer have not been widely evaluated in controlled
      trials. There is weak evidence to suggest that some interventions, such as
      structured group interventions, may lead to improvements in knowledge and
      understanding, in coping, anxiety, adjustment and wellbeing. More research is
      needed to investigate the comparative value of these interventions.

PMID- 14584018
TI  - Folic acid with or without vitamin B12 for cognition and dementia.
AB  - BACKGROUND: Folates are vitamins essential to the development of the central
      nervous system. Insufficient folate activity at the time of conception and early
      pregnancy can result in congenital neural tube defects. In adult life folate
      deficiency has been known for decades to produce a characteristic form of anaemia
      ("megaloblastic"). More recently degrees of folate inadequacy, not severe enough
      to produce anaemia, have been found to be associated with high blood levels of
      the amino acid homocysteine. Such degrees of folate inadequacy can arise because
      of insufficient folates in the diet or because of inefficient absorption or
      metabolic utilisation of folates due to genetic variations. Conventional criteria
      for diagnosing folate deficiency may be inadequate for identifying people capable
      of benefiting from dietary supplementation. High blood levels of homocysteine
      have been linked with the risk of arterial disease, dementia and Alzheimer's
      disease. There is therefore interest in whether dietary supplements of folic acid
      (an artificial chemical analogue of naturally occurring folates) can improve
      cognitive function of people at risk of cognitive decline associated with ageing
      or dementia, whether by affecting homocysteine metabolism or through other
      mechanisms. There is a risk that if folic acid is given to people who have
      undiagnosed deficiency of vitamin B12 it may lead to neurological damage. Vitamin
      B12 deficiency produces both an anaemia identical to that of folate deficiency
      but also causes irreversible damage to the central and peripheral nervous
      systems. Folic acid will correct the anaemia of vitamin B12 deficiency and so
      delay diagnosis but will not prevent progression to neurological damage. For this
      reason trials of folic acid supplements may involve simultaneous administration
      of vitamin B12. Apparent benefit from folic acid given in the combination would
      therefore need to be "corrected" for any effect of vitamin B12 alone. A separate
      Cochrane review of vitamin B12 and cognitive function is being prepared.
      OBJECTIVES: To examine the effects of folic acid supplementation, with or without
      vitamin B12, on elderly healthy and demented people, in preventing cognitive
      impairment or retarding its progress. SEARCH STRATEGY: Trials were identified
      from a search of the Cochrane Dementia and Cognitive Improvement Specialized
      Register Group on 9 April 2003 using the terms: folic acid, folate, vitamin B9,
      leucovorin, methyltetrahydrofolate, vitamin B12, cobalamin, cyanocobalamin,
      dementia, cognitive function, cognitive impairment, Alzheimer's disease, vascular
      dementia, mixed dementia and controlled trials. MEDLINE and EMBASE (both all
      years) were searched for additional trials on healthy people. SELECTION CRITERIA:
      All double-blind placebo-controlled randomized trials, in which supplements of
      folic acid with or without vitamin B12 were compared with placebo for elderly
      healthy people or people with any type of dementia or cognitive impairment. DATA
      COLLECTION AND ANALYSIS: The reviewers independently applied the selection
      criteria and assessed study quality. One reviewer extracted and analysed the
      data. In comparing intervention with placebo, weighted mean differences, and
      standardized mean difference or odds ratios were estimated. MAIN RESULTS: Four
      randomized controlled trials fulfilled the inclusion criteria for this review.
      One trial (Bryan 2002) enrolled healthy women, and three (Fioravanti 1997; Sommer
      1998; VITAL 2003) recruited people with mild to moderate cognitive impairment or
      dementia with or without diagnosed folate deficiency. Fioravanti 1997 enrolled
      people with mild to moderate cognitive impairment or dementia as judged by scores
      on the Mini-Mental State Examination (MMSE) and Global Deterioration Scale and
      with serum folate level<3ng/l. One trial (VITAL 2003) studied the effects of a
      combination of vitamin B12 and folic acid on patients with mild to moderate
      cognitive impairment due to Alzheimer's disease or mixed dementia. The analysis
      from the included trials found no benefit from folic acid with or without vitamin
      B12 in comparison with placebo on any measures of cognition and mood for healthy
      or cognitively impaired or demented people: Folic acid effect and healthy
      participants: there was no benefit from of oral 750 mcg folic acid per day for
      five weeks compared with placebo on measures of cognition and mood of 19 healthy
      women aged 65 to 92. Folic acid effect and people with mild to moderate cognitive
      decline or dementia: there were no statistically significant results in favour of
      folic acid with or without vitamin B12 on any measures of cognitive function.
      Scores on the Mini-Mental State Examination (MMSE) revealed no statistically
      significant benefit from 2 mg per day folic acid plus 1mg vitamin B12 for 12
      weeks when compared with placebo (WMD 0.39, 95% CI -0.43 to 1.21, P=0.35).
      Cognitive scores on the Alzheimer's Disease Scale (ADAS-Cog) showed no
      statistically significant benefit from 2 mg /day folic acid plus 1 mg /day
      vitamin B12 for 12 weeks compared with placebo (WMD 0.41, 95% -1.25 to 2.07,
      P=4.63). The Bristol Activities of Daily Living Scale (BADL) revealed no benefit
      from 2mg per day of folic acid plus 1 mg vitamin B12 for 12 weeks in comparison
      with placebo (WMD -0.57, 95%CI -1.95 to 0.81, P=0.42). None of the sub tests of
      the Randt Memory Test (RMT) showed statistically significant benefit from 15 mg
      of folic acid orally per day for 9 weeks when compared with placebo. One trial
      (Sommer 1998) reported a significant decline compared with placebo in two
      cognitive function tasks in demented patients who had received high doses of
      folic acid (10 mg /day) for unspecified periods. One trial (VITAL 2003) showed
      that 2 mg folic acid plus 1 mg vitamin B12 daily for 12 weeks significantly
      lowered serum homocysteine concentrations (P <0.0001). REVIEWER'S CONCLUSIONS:
      There was no beneficial effect of 750 mcg of folic acid per day on measures of
      cognition or mood in older healthy women. In patients with mild to moderate
      cognitive decline and different forms of dementia there was no benefit from folic
      acid on measures of cognition or mood. Folic acid plus vitamin B12 was effective
      in reducing the serum homocysteine concentrations. Folic acid was well tolerated
      and no adverse effects were reported. More studies are needed.

PMID- 14584019
TI  - Thermotherapy for treatment of osteoarthritis.
AB  - BACKGROUND: Osteoarthritis is a degenerative joint disease that affects mostly
      the weight-bearing joints in the knees and hips. As the affected joint
      degenerates pain and restriction of movement often occur. Inflammation can also
      occur sometimes resulting in edema of the joint with OA. Treatment focuses on
      decreasing pain and improving movement. OBJECTIVES: To determine the
      effectiveness of thermotherapy in the treatment of OA of the knee. The outcomes
      of interest were relief of pain, reduction of edema, and improvement of flexion
      or range of motion (ROM) and function. SEARCH STRATEGY: Two independent reviewers
      selected randomized and controlled clinical trials with participants with
      clinical and/or radiological confirmation of OA of the knee; and interventions
      using heat or cold therapy compared with standard treatment and/or placebo.
      Trials comparing head to head therapies, such as two different types of
      diathermy, were excluded. SELECTION CRITERIA: Randomized and controlled clinical
      trials including participants with clinical or radiographical confirmation of OA
      of the knee; and interventions using heat or cold compared to standard treatment
      or placebo were considered for inclusion. DATA COLLECTION AND ANALYSIS: Study
      results were extracted by two independent reviewers. Outcomes were continuous in
      nature (pain, strength, improvement) and were analyzed by weighted mean
      difference using a fixed effects model. Graphical data were used when table data
      were not available. MAIN RESULTS: Three randomized controlled trials, involving
      179 patients, were included in this review. The included trials varied in terms
      of design, outcomes measured, cryotherapy or thermotherapy treatments and overall
      methodological quality. In one trial, administration of 20 minutes of ice
      massage, 5 days per week, for 3 weeks, compared to control demonstrated a
      clinically important benefit for knee OA on increasing quadriceps strength (29%
      relative difference). There was also a statistically significant improvement, but
      no clinical benefit in improving knee flexion ROM (8% relative difference) and
      functional status (11% relative difference). Another trial showed that cold packs
      decreased knee edema. REVIEWER'S CONCLUSIONS: Ice massage compared to control had
      a statistically beneficial effect on ROM, function and knee strength. Cold packs
      decreased swelling. Hot packs had no beneficial effect on edema compared with
      placebo or cold application. Ice packs did not effect pain significantly compared
      to control in patients with OA. More well designed studies with a standardized
      protocol and adequate number of subjects are needed to evaluate the effect of
      thermotherapy in the treatment of OA of the knee.

PMID- 14584020
TI  - Risedronate for the prevention and treatment of postmenopausal osteoporosis.
AB  - BACKGROUND: Postmenopausal osteoporosis results in an increased susceptibility to
      low-trauma fractures due to reduced bone volume and microarchitectural
      deterioration. Risedronate, a third generation bisphosphonate, has been shown in
      multiple clinical trials to reduce fracture risk and improve bone mineral density
      in postmenopausal women with osteoporosis. First and second generation
      bisphosphonates are known to have gastrointestinal side-effects and risedronate
      may be better tolerated. OBJECTIVES: To systematically review the efficacy of
      risedronate on bone density, and fracture reduction in postmenopausal women.
      SEARCH STRATEGY: The Cochrane Controlled Trials Registry Medline, and Current
      Contents were searched from 1990 - 2001. The electronic search was supplemented
      by handsearching four osteoporosis journals and their conference proceedings, as
      well as contacting content experts and industry sources for unpublished data.
      SELECTION CRITERIA: We included eight trials that randomised women to risedronate
      or an alternative (placebo or calcium and /or vitamin D) and measured bone
      mineral density for at least one year. DATA COLLECTION AND ANALYSIS: For each
      trial three independent reviewers assessed the methodological quality and
      abstracted data. Data was extracted for outcomes of fracture, bone mineral
      density and adverse events. The more conservative random effects model was used
      to pool data. The quality of trials was assessed according to the Jadad five
      point scale. MAIN RESULTS: Both vertebral and non-vertebral fractures were
      statistically and clinically reduced with risedronate. Eleven out of one hundred
      women who received risedronate had a vertebral fracture compared to 17 out of one
      hundred of those who received an alternative treatment (pooled relative risk for
      vertebral fractures of 0.64 (95% CI 0.52 - 0.77). Three percent of participants
      who received risedronate had a non-vertebral fracture compared to 4.6% of those
      who received an alternative treatment (pooled relative risk for nonvertebral
      fractures of 0.73 (95% CI 0.61 - 0.87). The weighted mean difference for the
      percent change from baseline for bone mineral density with 5 mg daily for lumbar
      spine, femoral neck and trochanter was 4.54% (95%CI 4.12 - 4.97), p<0.01; 2.75%
      (95% CI 2.32 - 3.17), p<0.01; and 4.38% (95% CI 3.51 - 5.25), p<0.01
      respectively. REVIEWER'S CONCLUSIONS: There is good evidence for the efficacy of
      risedronate in the reduction of both vertebral and non-vertebral fractures. In
      addition, there is evidence from randomized trials that risedronate is able to
      achieve this without increasing risk for overall withdrawals due to adverse
      effects.

PMID- 14584021
TI  - Etanercept for the treatment of rheumatoid arthritis.
AB  - BACKGROUND: Etanercept is a soluble tumour necrosis factor alpha-receptor DMARD
      for the treatment of rheumatoid arthritis (RA). OBJECTIVES: To assess the
      efficacy and safety of etanercept for the treatment of RA. SEARCH STRATEGY: Five
      electronic databases were searched from 1966 to February 2003 with no language
      restriction. SELECTION CRITERIA: All randomized controlled trials (minimum 6
      month duration) comparing three possible combinations 1) etanercept (10 mg or 25
      mg twice weekly) with methotrexate (MTX) to MTX alone 2) etanercept to MTX, or 3)
      etanercept to placebo were eligible. DATA COLLECTION AND ANALYSIS: Two reviewers
      extracted data and assessed the methodological quality of the trails. The
      American College of Rheumatology (ACR) core set of disease activity measures for
      RA clinical trials, radiographic, withdrawals and toxicity outcomes were
      analyzed. MAIN RESULTS: Three trials were included in this review. Two trials
      compared an experimental group who were started on etanercept compared to a
      control group; both groups had the same ongoing background therapy of
      nonsteroidals in both trials plus in one trial one group was on stable
      methotrexate. In these two trials the ACR 20, ACR 50 and ACR 70 response rates at
      6 months were statistically significantly and clinically important with
      etanercept 25 mg subcutaneous injections (SC) twice weekly. Sixty-four percent of
      people receiving etanercept ache vied an ACR 20 response compared to 15% of
      controls and the number needed to treat (NNT) with etanercept is 2 people. Thirty
      nine percent of those receiving etanercept achieved an ACR 50 response compared
      to 4% of taking control treatment and the NNT is three. Fifteen percent of people
      taking etanercept achieved an ACR 70 compared to 1% of controls with a NNT of 7
      people. In the third trial of starting etanercept compared to starting
      methotrexate the number of participants who achieved an ACR 20, 50 or response at
      6 and 12 months were not statistically significant for either etanercept dose.
      Etanercept treatment showed a statistically significantly and clinically
      important affect on joint damage as measured by the Sharp erosion score. Among
      participants who received etanercept 72% had no increase in their erosion score
      compared to 60% of participants in the methotrexate group. Withdrawal and
      toxicity results were acceptable. REVIEWER'S CONCLUSIONS: Etanercept 25 mg SC
      twice weekly was more efficacious than control treatment for ACR 20, 50 and 70 at
      6 months, and over 12 months it slowed joint damage.

PMID- 14584023
TI  - An IQGAP-like protein is involved in actin assembly together with Cdc42 in the
      sea urchin egg.
AB  - We isolated a gene homologous to human cdc42 (ucdc42) from a sea urchin cDNA
      library. The GTPgammaS-bound UCdc42 induced actin assembly in sea urchin egg
      extract. Proteins that are involved in this actin assembly system were searched
      using UCdc42-bound agarose beads. A 180-kDa protein (p180), which showed a
      homology to human IQGAPs, bound to the GTPgammaS-UCdc42 beads. Immunodepletion of
      p180 from the sea urchin egg extract abolished this actin assembly on the UCdc42
      beads. Immunofluorescent localization of p180 was similar to that of the actin
      cytoskeleton in the egg cortex and it was concentrated in the cleavage furrow
      during cytokinesis. A possible role of p180 in actin assembly is discussed.

PMID- 14584024
TI  - The molecular biology of Euglena gracilis. XV. Recovery from centrifugation
      induced stratification.
AB  - The contents of Euglena gracilis cells can be separated in vivo by
      ultracentrifugation. Within the unbroken cell, each set of components forms a
      distinct layer according to their respective densities. The degree of segregation
      increases with both the g-force and the time of centrifugation, up to a maximum
      at 100,000 x g for 1 h, when six distinct strata can be observed. When returned
      to normal growth conditions, essentially all the cells return to the normal state
      and growth pattern. Greater g-forces or longer exposures do not alter the
      observable strata, but the ability of the cells to recover is diminished. Smaller
      g-forces result in less separation of cellular contents and all cells recover,
      even after 18 h of exposure. Euglena cells stratified at 100,000 x g for 1 h were
      returned to normal growth conditions; recovery was followed microscopically and
      by the rate of utilization of oxygen as well as that of the single carbon source.
      The cells recovered their normal state within 1 to 2 h, which is only a tenth of
      the normal doubling time. The mechanism for this recovery involves a natural
      process of change in cell shape caused by contraction and relaxation of the
      pellicle, a cell surface structure.

PMID- 14584022
TI  - Calcium supplementation on bone loss in postmenopausal women.
AB  - BACKGROUND: Although calcium is one the simplest and least expensive strategies
      for preventing osteoporotic fractures calcium supplementation is nevertheless not
      without controversy (Kanis 1989; Nordin 1990). The Food and Drug Administration
      in the US has permitted a bone health claim for calcium-rich foods, and the NIH
      in its Consensus Development Process approved a statement that high calcium
      intake reduces the risk of osteoporosis. OBJECTIVES: To assess the effects of
      calcium on bone density and fractures in postmenopausal women. SEARCH STRATEGY:
      We searched Cochrane Controlled Register, MEDLINE and EMBASE up to 2001, and
      examined citations of relevant articles and proceedings of international
      meetings. SELECTION CRITERIA: Trials that randomized postmenopausal women to
      calcium supplementation or usual calcium intake in the diet and reported bone
      mineral density of the total body, vertebral spine, hip, or forearm or recorded
      the number of fractures, and followed patients for at least one year were
      considered for inclusion. DATA COLLECTION AND ANALYSIS: Three independent
      reviewers assessed the methodologic quality and extracted data for each trial.
      For each bone density site (lumbar spine, total body, combined hip and combined
      forearm), we calculated the weighted mean difference in bone density between
      treatment and control groups using the percentage change from baseline. We
      constructed regression models in which the independent variables were year and
      dose, and the dependent variable was the effect size. This regression was used to
      determine the years across which pooling was appropriate. Heterogeneity was
      assessed. For each fracture analysis we calculated a risk ratio. MAIN RESULTS:
      Fifteen trials, representing 1806 participants, were included. Calcium was more
      effective than placebo in reducing rates of bone loss after two or more years of
      treatment. The pooled difference in percentage change from baseline was 2.05%
      (95% CI 0.24 to 3.86) for total body bone density, 1.66% (95% CI 0.92 to 2.39)
      for the lumbar spine at 2 years, 1.60% (95% CI 0.78 to 2.41) for the hip, and
      1.91% (95% CI 0.33 to 3.50) for the distal radius. The relative risk of fractures
      of the vertebrae was 0.79 (95% CI 0.54 to 1.09); the relative risk for non
      vertebral fractures was 0.86 (95% CI 0.43 to 1.72). REVIEWER'S CONCLUSIONS:
      Calcium supplementation alone has a small positive effect on bone density. The
      data show a trend toward reduction in vertebral fractures, but it is unclear if
      calcium reduces the incidence of non vertebral fractures.

PMID- 14584025
TI  - Vaults bind directly to microtubules via their caps and not their barrels.
AB  - Vaults are large (13 Mda) ribonucleoprotein particles that are especially
      abundant in multidrug resistant cancer cells and have been implicated in
      nucleocytoplasmic drug transport. To understand how these large barrel-shaped
      complexes are transported through the cytosol, we examined the association of
      vaults with microtubules both in vitro and in vivo. Within cells, a subpopulation
      of vaults clearly associates with microtubules, and these vaults remain
      associated with tubulin dimers/oligomers when microtubules are disassembled by
      nocodazole treatment. In vitro, a microtubule-pull down assay using highly
      purified rat vaults and reassembled microtubules reveals that vaults exhibit
      concentration-dependent binding to microtubules that does not require the
      carboxyl terminal end of tubulin. Remarkably, negative staining for electron
      microscopy reveals that vault binding to microtubules is mediated by the vault
      caps; more than 82% of bound vaults attach to the microtubule lattice with their
      long axes perpendicular to the long axis of the microtubule. Five to six vault
      particles were bound per micron of microtubule, with no crosslinking of
      microtubules observed, suggesting that only one end of the vault can bind
      microtubules. Taken together, the data support the model of vaults as barrel
      shaped containers that transiently interact with microtubules.

PMID- 14584026
TI  - Does axonemal dynein push, pull, or oscillate?
AB  - Dynein is the molecular motor that provides motive force in cilia and flagella.
      Dynein is anchored to the A-subtubule of the outer doublets by a club-shaped
      extension called the stem, which supports the large globular head of the
      molecule. Dynein forms an attachment or cross-bridge to the B-subtubule of the
      adjacent outer doublet through a slender appendage extending from the head that
      is called the stalk or alternately the B-link. It is generally thought that the B
      link mediates the interdoublet transfer of force that bends the flagellum. This
      requires that energy released at the site of ATP hydrolysis, located in the
      globular head, be transferred as mechanical work to the microtubule binding site
      at the tip of the B-link. It has been proposed that this is accomplished by a
      sideways or rotational translocation of the B-link caused by a rotation of the
      globular head. An estimate of the stiffness of the B-link and stem derived from
      the recently published data of Burgess et al. [2003: Nature 421:715-718] yields a
      maximum stiffness of 0.47 pN/nm for the B-link and 0.1 pN/nm for the stem. The B
      link stiffness would allow transfer of 3.8 pN of force in response to an 8-nm
      displacement of the B-link tip. However, if as proposed the globular head of the
      dynein heavy chain is supported by the stem, the B-link and stem elasticity are
      in series. Thus, the flexibility of the stem would limit the force that can be
      transferred laterally by the entire dynein heavy chain to 0.6 pN at 8 nm
      displacement. This force is insufficient to support flagellar motility. So, if
      the stem were the only support for the globular head, then force would have to be
      transmitted linearly along the axis defined by the stem and B-link. Because this
      configuration is never observed, the hypothesis that dynein generates force by
      lateral displacement of the B-link is more attractive, but requires that the
      globular head of the dynein is stabilized by an additional means of support
      during the power stroke. We propose that the microtubule affinity of the tip of
      the B-link is independent of the ATP-dependent powerstroke, and that detachment
      from the B-subtubule is regulated by tension. A dynein cross-bridge cycle that
      incorporates an anchored head, together with a ratchet-like mechanism for
      microtubule translocation by the B-link, would have distinct advantages. This
      mechanism may reconcile dynein oscillation and interdoublet sliding within one
      cross-bridge mechanism.

PMID- 14584027
TI  - LIS1 association with dynactin is required for nuclear motility and genomic union
      in the fertilized mammalian oocyte.
AB  - Mutations in the human LIS1 gene cause the devastating brain disorder
      lissencephaly. LIS1 also regulates microtubule dynamics; it interacts with the
      molecular motor cytoplasmic dynein and its cofactor dynactin, and is necessary
      for neuronal migration. Recently, LIS1 has been suggested to mediate pronuclear
      migration during fertilization. Here we use rhesus monkey and bovine oocytes, as
      well as pronucleate-stage bovine zygotes, to determine: Lis1 RNA expression using
      reverse transcription-polymerase chain reaction; LIS1 protein association with
      dynactin using immunoprecipitation, Western blot analysis, and
      immunocytochemistry; and LIS1 function in mediating genomic union using antibody
      transfection. We find that Lis1 RNA expression increases during fertilization,
      that LIS1 and dynactin subunit p150/(Glued) co-immunoprecipitate and co-localize
      to pronuclear surfaces, and that anti-LIS1 antibodies transfected into zygotes
      dramatically inhibit pronuclear migration and apposition. LIS1 is, therefore,
      essential to mediate genomic union in a process that involves the dynein-dynactin
      complex. These results shed light on an additional role for LIS1 and raise
      implications for human reproduction.

PMID- 14584028
TI  - Actin-based centripetal flow: phosphatase inhibition by calyculin-A alters flow
      pattern, actin organization, and actomyosin distribution.
AB  - Previous studies have suggested that the actin-based centripetal flow process in
      sea urchin coelomocytes is the result of a two-part mechanism, actin
      polymerization at the cell edge coupled with actomyosin contraction at the cell
      center. In the present study, we have extended the testing of this two-part model
      by attempting to stimulate actomyosin contraction via treatment of coelomocytes
      with the phosphatase inhibitor Calyculin A (CalyA). The effects of this drug were
      studied using digitally-enhanced video microscopy of living cells combined with
      immunofluorescent localization and scanning electron microscopy. Under the
      influence of CalyA, the coelomocyte actin cytoskeleton undergoes a radical
      reorganization from a dense network to one displaying an array of tangential arcs
      and radial rivulets in which actin and the Arp2/3 complex concentrate. In
      addition, the structure and dynamics of the cell center are transformed due to
      the accumulation of actin and membrane in this region and the constriction of the
      central actomyosin ring. Physiological evidence of an increase in actomyosin
      based contractility following CalyA treatment was demonstrated in experiments in
      which cells generated tears in their cell centers in response to the drug.
      Western blotting and immunofluorescent localization with antibodies against the
      phosphorylated form of the myosin regulatory light chain (MRLC) suggested that
      the demonstrated constriction of actomyosin distribution was the result of CalyA
      induced phosphorylation of MRLC. Overall, the results suggest that there is
      significant cross talk between the two underlying mechanisms of actin
      polymerization and actomyosin contraction, and indicate that changes in
      actomyosin tension may be translated into alterations in the structural
      organization of the actin cytoskeleton.

PMID- 14584029
TI  - Larval development of Myzostoma cirriferum (Myzostomida).
AB  - The larval development of Myzostoma cirriferum is described by means of SEM, TEM,
      and cLSM. It is similar to that of other myzostomids and includes three stages:
      the protrochophore, the trochophore, and the metatrochophore. The protrochophore
      is a ball-shaped larva present in culture from 18-48 h after egg laying. It has
      no internal organs and its body is made of three cell types: covering cells and
      ciliated cells that are external and surrounded by a cuticle, and resting cells
      that fill the blastocoel. The trochophore is a pear-shaped larva that develops 20
      72 h after egg laying; the body includes the same three cell types as the
      previous stage. The metatrochophore is a pear-shaped larva that develops between
      40 h and 14 days and is characterized by the presence of two bundles of four
      chaetae. When fully developed, the metatrochophore has a digestive system (made
      of a pharynx, an esophagus, and a blind digestive pouch), two pairs of
      protonephridia, and a nervous system composed of a supraesophageal ganglion,
      circumesophageal connectives, and dorsal and ventral nerves. Metamorphosis
      generally occurs 7 days after egg laying. At that time, the metatrochophore loses
      its chaetae and becomes pleated ventrally. This ultrastructural analysis suggests
      that chaetae and the five ventral longitudinal nerve cords of M. cirriferum
      metatrochophores are homologous structures to those observed in some polychaete
      trochophores. Coupled with recent phylogenetic analyses, where the Myzostomida
      are placed outside the Annelida, homologies between myzostomid and polychaete
      larvae support the view that a trochophore appeared early during the spiralian
      evolution.

PMID- 14584030
TI  - Wing design and morphology of the harbor porpoise dorsal fin.
AB  - The correlation between skin structure and hydrodynamic design of the dorsal fin
      of the harbor porpoise (Phocoena phocoena) was examined. For the study of fin
      morphology and geometry, a scheme of sampling representing a two-parameter mesh
      on the fin surface was used. At each data point the thickness of the epidermis,
      papillary and subpapillary layers of the dermis, the ligamentous layer of the
      fin, as well as the angle formed by the direction of dermal ridges and the fin
      root chord were measured. On the basis of fin cross-sections the three
      dimensional surface models of the fin in a 1 : 1 scale were created with a CAD
      program. The shape of the model was evaluated by the wing and hydrofoil
      parameters (angle of leading edge sweep, leading edge radius, maximum thickness
      of the fin cross-section, and position of maximum thickness from the leading
      edge). Hydrodynamic performance of the fin cross-sections was studied with a CFD
      program. Regional variability of the parameters of morphology was compared with
      spanwise variability of the parameters of cross-sectional geometry. It was found
      that skin structure parameters correlate with the hydrodynamically relevant
      parameters of the fin and fin cross-sections. Regularities of skin structure of
      the harbor porpoise dorsal fin are considered indirect evidence of the adaptation
      of porpoise skin to the fin flow.

PMID- 14584031
TI  - Cytological evaluation of spermatogenesis within the germinal epithelium of the
      male European wall lizard, Podarcis muralis.
AB  - The annual cytological changes to the male germinal epithelium were investigated
      in an introduced population of European wall lizards (Podarcis muralis).
      Testicular tissues were collected, embedded, sectioned by an ultramicrotome, and
      stained with the PAS procedure followed by a toluidine counterstain.
      Spermatogenesis in the lizard is divided into the proliferative, meiotic, and
      maturational phases. Wall lizards have a prenuptial pattern of spermatogenesis,
      where sperm development begins immediately prior to and continues through the
      months of breeding (April-June). The testis then involutes, undergoes a short
      period of quiescence, and recrudescence commences in mid-July. Germ cells undergo
      proliferation, meiosis, and the early stages of spermiogenesis (maturation) from
      late July through December. However, the late stages of spermiogenesis are
      retarded from December through February. Spermiogenesis continues at an
      accelerated pace from March through May, leading to a single massive spermiation
      event through the month of June. Although spatial relationships are seen between
      germ cells within the seminiferous epithelium, accumulation of spermatids during
      winter and acceleration of elongation in spring prevents determination of
      consistent cellular associations between early and late developing germ cells
      within the wall lizard testis. This temporal germ cell development is different
      from the consistent spatial development seen within seasonally breeding birds and
      mammals and may represent an evolutionary intermediate in terms of amniotic germ
      cell development.

PMID- 14584032
TI  - Electron and light microscopic study of various glands and the secretions
      released into the environment by the turbellarian Urastoma cyprinae.
AB  - The turbellarian Urastoma cyprinae (Graff) occurs on the gills of various bivalve
      species including the mussel Mytilus galloprovinciallis, where it is known to
      cause serious damage. More recently, it has been shown that the worms are
      strongly attracted to the gill of the American oyster (Crassostrea virginica) and
      are capable of inducing changes to the composition of proteolytic enzymes of the
      host mucus. Such changes may be attributable to secretory products released by
      the worms. Mucous glands (11-18 mum in diameter) produce minute spherules (0.7
      0.9 mum in diameter) tightly bound together. The glands occupy approximately 20%
      of the body volume and are the most voluminous secretory organs in the worm. The
      smaller rhabdoid glands are unevenly distributed throughout the peripheral
      parenchyma and contain secretory granules of 0.35-1.2 mum in diameter. The latter
      occur most prominently along the distal margins of the epidermis. The frontal
      pole of U. cyprinae consists of a complex assembly of mucous and rhabdoid gland
      cells as well as other glandular structures. Collectively, these bodies release
      their contents to the outside via narrow gland necks. The overall organization is
      consistent with the frontal gland previously described for other free-living
      turbellarians, including other rhabdocoels. A variety of secretory products,
      displaying variations in staining properties, have likewise been identified in
      association with the body wall from other regions of the worm. This work attempts
      to gain a better appreciation of the secretory structures associated with the
      worm tegument, focusing primarily on the widespread mucous and rhabdoid glands.
      The secretions play a role in host-parasite interactions.

PMID- 14584033
TI  - Sertoli cells in the testis of caecilians, Ichthyophis tricolor and Uraeotyphlus
      cf. narayani (Amphibia: Gymnophiona): light and electron microscopic perspective.
AB  - The caecilians have evolved a unique pattern of cystic spermatogenesis in which
      cysts representing different stages in spermatogenesis coexist in a testis
      lobule. We examined unsettled issues relating to the organization of the
      caecilian testis lobules, including the occurrence of a fatty matrix, the
      possibility of both peripheral and central Sertoli cells, the origin of Sertoli
      cells from follicular cells, and the disengagement of older Sertoli cells to
      become loose central Sertoli cells. We subjected the testis of Ichthyophis
      tricolor (Ichthyophiidae) and Uraeotyphlus cf. narayani (Uraeotyphliidae) from
      the Western Ghats of Kerala, India, to light and transmission electron
      microscopic studies. Irrespective of the functional state of the testis, whether
      active or regressed, Sertoli cells constitute a permanent feature of the lobules.
      The tall Sertoli cells adherent to the basal lamina with basally located
      pleomorphic nuclei extend deeper into the lobule to meet at the core. There they
      provide for association of germ cells at different stages of differentiation, an
      aspect that has earlier been misconceived as the fatty matrix. Germ cells up to
      the 4-cell stage remain in the intercalating region of the Sertoli cells and they
      are located at the apices of the Sertoli cells from the 8-cell stage onwards. The
      developing germ cells are intimately associated with the Sertoli cell adherent to
      the basal lamina until spermiation. There are ameboid cells in the core of the
      lobules that appear to interact with the germ cells at the face opposite to their
      attachment with the Sertoli cells. Adherence of the Sertoli cells to the basal
      lamina is a permanent feature of the caecilian testicular lobules. The ameboid
      cells in the core are neither Sertoli cells nor their degeneration products.

PMID- 14584034
TI  - Anatomy of the crocodilian spinal vein.
AB  - The crocodilian spinal vein is remarkably robust yet historically overlooked.
      Using corrosion casting, we describe the anatomy of this vessel and its
      connections with the caval and hepatic venous systems in representatives from
      four crocodilian genera. The spinal vein arises from an enlarged occipital sinus
      over the medulla and extends the entire length of the vertebral column. Unlike in
      squamate reptiles, the spinal vein is single (nonplexiform), voluminous, and
      situated dorsal to the spinal cord, and plexi lateral to the cord span between
      emerging intercostal veins. The connections with the other venous systems are
      otherwise similar to those in other tetrapods. The overall anatomy of this vessel
      and its abundant connections with the other venous systems indicate it likely
      plays a primary role in returning blood to the heart from all parts of the body.
      Preliminary studies of function suggest that this vessel could also play an
      adaptive role during basking and diving.

PMID- 14584035
TI  - Mechanisms of internalization of apoptotic and necrotic L929 cells by a
      macrophage cell line studied by electron microscopy.
AB  - Rapid and efficient phagocytic removal of dying cells is a key feature of
      apoptosis. In necrotic caspase-independent modes of death, the role and extent of
      phagocytosis is not well documented. To address this issue, we studied at the
      ultrastructural level the phagocytic response to dying cells in an in vitro
      phagocytosis assay with a mouse macrophage cell line (Mf4/4). As target cells,
      murine L929sAhFas cells were induced to die by TNFR1-mediated necrosis or by Fas
      mediated apoptosis. Apoptotic L929sAhFas cells are taken up by complete
      engulfment of apoptotic bodies as single entities forming a tight-fitting
      phagosome, thus resembling the "zipper"-like mechanism of internalization. In
      contrast, primary and secondary necrotic cells were internalized by a
      macropinocytotic mechanism with formation of multiple ruffles by the ingesting
      macrophage. Ingestion of necrotic cellular material was invariably taking place
      after the integrity of the cell membrane was lost and did not occur as discrete
      particles, in contrast to apoptotic material that is surrounded by an intact
      membrane. Although nuclei of necrotic cells have been observed in the vicinity of
      macrophages, no uptake of necrotic nuclei was observed. The present report
      provides a basis for future studies aimed at discovering molecular pathways that
      precede these diverse mechanisms of uptake.

PMID- 14584036
TI  - Viviparous lizard, Eulamprus tympanum, shows changes in the uterine surface
      epithelium during early pregnancy that are similar to the plasma membrane
      transformation of mammals.
AB  - The "plasma membrane transformation" describes a series of ultrastructural,
      biochemical, and morphological changes that occur in the uterus of many mammals
      at the time of blastocyst attachment. These changes, regardless of placental type
      or length of gestation, include alterations to microvillar length and density and
      the presence or absence of pinopods or uterodomes. Scanning electron microscopy
      (SEM) was used to 1) document the topographical ultrastructure of the uterus of
      Eulamprus tympanum, an eastern Australian viviparous skink with a simple
      chorioallantoic placenta, for the first time; and 2) determine whether changes
      identified as "plasma membrane transformation" in mammals occur in E. tympanum.
      Tissues collected over three seasons from nonreproductive subadult females,
      preovulatory, postovulatory, and early to mid-gestational females were examined.
      At low magnification the uterine epithelium of subadults displays a distinctive
      pattern of tissue folding that includes rectangular areas of tissue delineated by
      deep lateral and transverse folds. At higher magnification, the uterine
      epithelium surface is composed of two dominant cell types, i.e., those covered by
      microvilli and ciliated cells. The folding pattern observed in subadults is less
      evident in vitellogenic females and the cell surfaces appear highly secretory,
      with bulging cell apices. Tissue from postovulatory lizards has no distinctive
      folding pattern and cell surfaces are frequently smooth and lack microvilli.
      Uterine egg chambers lack ciliated cells at the embryonic pole, but display
      abundant secretory droplets. Thus, the uterus of E. tympanum undergoes a plasma
      membrane transformation. The scope of this transformation is not fully understood
      but may be related to the complexity of placental structure and the development
      of the embryo/fetus at parturition.

PMID- 14584037
TI  - Prey transport in "palatine-erecting" elapid snakes.
AB  - Cobras and mambas are members of a group of elapid snakes supposedly united by
      the morphology and inferred behavior of their palatine bone during prey transport
      (palatine erectors). The palatine erectors investigated (Dendroaspis polylepis,
      Naja pallida, Ophiophagus hannah, Aspidelaps scutatus, A. lubricus) show
      differences in the morphology of their feeding apparatus that do not affect the
      overall behavior of the system. We delineated the structures directly involved in
      producing palatine erection during prey transport. Palatine erection can be
      achieved by a colubroid muscle contraction pattern acting on a palato-pterygoid
      bar with a movable palato-pterygoid joint and a palatine that is stabilized
      against the snout. The palatine characters originally proposed to cause palatine
      erection are not required to produce the behavior and actually impede it in Naja
      pallida. Palatine-erecting elapids share a fundamental design of the palato
      maxillary apparatus with all higher snakes. A set of plesiomorphic core
      characters is functionally integrated to function in prey transport using the
      pterygoid walk. Variant characters are either part of a structural periphery
      unrelated to the core structures that define function or patterns of variation
      are subordinate character sets operating within functional thresholds of a single
      system.

PMID- 14584038
TI  - Sphingosine 1-phosphate induces cell contraction via calcium-independent/Rho
      dependent pathways in undifferentiated skeletal muscle cells.
AB  - We have previously shown that sphingosine 1-phosphate (S1P) can induce
      intracellular Ca(2+) mobilization and cell contraction in C2C12 myoblasts and
      that the two phenomena are temporally unrelated. Although Ca(2+)-independent
      mechanisms of cell contraction have been the focus of numerous studies on Ca(2+)
      sensitization of smooth muscle, comparatively less studies have focused on the
      role that these mechanisms play in the regulation of skeletal muscle
      contractility. Phosphorylation and activation of myosin by Rho-dependent kinase
      mediate most of Ca(2+)-independent contractile responses. In the present study,
      we examined the potential role of Rho/Rho-kinase cascade activation in S1P
      induced C2C12 cell contraction. First, we showed that depletion of Ca(2+), by pre
      treatment with BAPTA, did not affect S1P-induced myoblastic contractility,
      whereas it abolished S1P-induced Ca(2+) transients. These results correlated with
      the absence of troponin C and with the immature cytoskeletal organization of
      these cells. Experimental evidence demonstrating the involvement of Rho pathway
      in S1P-stimulated myoblast contraction included: the activation/translocation of
      RhoA to the membrane in response to agonist-stimulation in cells depleted of
      Ca(2+) and the inhibition of dynamic changes of the actin cytoskeleton in cells
      where Rho functions had been inhibited either by overexpression of RhoGDI, a
      physiological inhibitor of GDP dissociation from Rho proteins, or by pretreatment
      with Y-27632, a specific Rho kinase inhibitor. Contribution of protein kinase C
      in this cytoskeletal rearrangement was also evaluated. However, the pretreatment
      with Go6976 or rottlerin, specific inhibitors of PKC alpha and PKC delta,
      respectively, failed to inhibit the agonist-induced myoblastic contraction.
      Single particle tracking of G-actin fluorescent probe was performed to
      statistically evaluate actin cytoskeletal dynamics in response to S1P.
      Stimulation with S1P was also able to increase the phosphorylation level of
      myosin light chain II. In conclusion, our results strongly suggest that Ca(2+)
      independent/Rho-Rho kinase-dependent pathways may exert an important role in S1P
      induced myoblastic cell contraction.

PMID- 14584039
TI  - Sialoadenectomy alters liver cell turn-over and function in mice.
AB  - In rodents, submandibular salivary glands accumulate a number of biologically
      active peptides, and release some of them to both saliva and the bloodstream.
      Surgical removal of these glands (sialoadenectomy) alters the ability of the
      liver to regenerate after partial hepatectomy. We show here that 5 weeks after
      surgery, the liver of sialoadenectomized mice contained 40% fewer hepatocytes
      than the liver of sham-operated mice. We did not obtain evidence of necrotic cell
      death after surgery. In contrast, sialoadenectomy transiently increased apoptotic
      hepatocyte death, as revealed by terminal deoxynucleotidyl transferase(TdT)
      mediated dUTP nick-end labeling (TUNEL) assay. DNA synthesis was determined in
      vivo by the incorporation of bromo-deoxyuridine (BrdU) into hepatocyte nuclei.
      BrdU-labeling progressively increased after sialoadenectomy. We conclude that
      sialoadenectomy induced a transient wave of apoptotic cell death followed by a
      rise in DNA synthesis but not by cell division. This reduced cell number but
      increased mean cell volume. In spite of these alterations in cellularity, the
      liver responded adequately to several stressful conditions, as judged by the lack
      of any differential effect of sialoadenectomy on liver glycogen and plasma
      glucose concentration after immobilization, aggressive encounter, or fasting.
      However, the liver of sialoadenectomized mice was more sensitive to the effect of
      a non-lethal dose of bacterial lipopolysaccharide (LPS) combined with d
      galactosamine, as shown by the enhanced rise in plasma alanine aminotransferase
      and aspartate aminotransferase, and liver myeloperoxidase (MPO) activities. All
      these results indicate that a submandibular salivary glands-liver axis is
      involved in the maintenance of liver structure in mice. A disturbance of this
      axis induces an adaptive response that preserves the metabolic function of the
      liver but renders it more sensitive to bacterial endotoxins.

PMID- 14584040
TI  - Overexpression of thioredoxin reductase 1 regulates NF-kappa B activation.
AB  - Thioredoxin reductase (TrxR) is a flavoprotein that contains a C-terminal
      penultimate selenocysteine (Sec) and has an ability to reduce thioredoxin (Trx),
      which regulates the activity of NF-kappa B. To date, three TrxR isozymes, TrxR1,
      TrxR2, and TrxR3, have been identified. In the present study, we found that among
      these isozymes only TrxR1 was induced by tumor necrosis factor-alpha (TNF alpha)
      in vascular endothelial cells. Furthermore, the overexpression of TrxR1 enhanced
      TNF alpha-induced DNA-binding activity of NF-kappa B and NF-kappa B-dependent
      gene expression. The catalytic Sec residue of TrxR1, which is essential for
      reducing Trx, was required for this NF-kappa B activation, and aurothiomalate, an
      inhibitor of TrxR, suppressed TNF alpha-induced activation of NF-kappa B and the
      expression of NF-kappa B-targeted proinflammatory genes such as E-selectin and
      cyclooxygenase-2. These results suggest that TrxR1 may act as a positive
      regulator of NF-kappa B and may play an important role in the cellular
      inflammatory response.

PMID- 14584041
TI  - Cripto-1 overexpression leads to enhanced invasiveness and resistance to anoikis
      in human MCF-7 breast cancer cells.
AB  - Cripto-1 (CR-1) is an epidermal growth factor (EGF)-CFC protein that has been
      shown to signal through nodal/Alk-4, PI3K/Akt, and/or ras/raf/MEK/MAPK pathways
      in mammalian cells, and that is frequently expressed in human primary breast
      carcinomas. In the present study, the human estrogen receptor positive, MCF-7
      breast cancer cell line, that expresses low levels of endogenous CR-1, was
      transfected with a CR-1 expression vector. MCF-7 CR-1 cells expressed high levels
      of a 25 kDa recombinant CR-1 protein that was not detected in MCF-7 cells
      transfected with a control vector (MCF-7 neo). Overexpression of CR-1 did not
      induce an estrogen independent phenotype in MCF-7 cells. In fact, MCF-7 CR-1
      cells showed a response to exogenous estrogens that was similar to MCF-7 neo
      cells, and failed to grow in immunosuppressed mice in absence of estrogen
      stimulation. However, MCF-7 CR-1 cells showed a rate of proliferation in serum
      free conditions, and an ability to form colonies in soft-agar that were higher as
      compared with MCF-7 neo cells. More importantly, overexpression of CR-1 enhanced
      the resistance to anoikis and the invasion ability of MCF-7 cells. MCF-7 CR-1
      cells showed levels of activation of both Akt and Smad-2 that were significantly
      higher as compared with MCF-7 neo. These findings suggest that CR-1
      overexpression might be associated with the progression towards a more aggressive
      phenotype in breast carcinoma, through the activation of both Akt and Smad-2
      signalling pathways.

PMID- 14584042
TI  - Extracellular inorganic phosphate regulates gibbon ape leukemia virus receptor
      2/phosphate transporter mRNA expression in rat bone marrow stromal cells.
AB  - In mammalian cells, several observations indicate not only that phosphate
      transport probably regulates local inorganic phosphate (Pi) concentration, but
      also that Pi affects normal cellular metabolism, which in turn regulates
      apoptosis and the process of mineralization. To elucidate how extracellular Pi
      regulates cellular functions of pre-osteoblastic cells, we investigated the
      expression of type III sodium (Na)-dependent Pi transporters in rat bone marrow
      stromal cells and ROB-C26 pre-osteoblastic cells. The mRNA expression level of
      gibbon ape leukemia virus receptor (Glvr)-2 was increased by the addition of Pi
      in rat bone marrow stromal cells, but not in ROB-C26 or normal rat kidney (NRK)
      cells. In contrast, the level of Glvr-1 mRNA was not altered by the addition of
      extracellular Pi in these cells. The induction of Glvr-2 mRNA by Pi was inhibited
      in the presence of cycloheximide (CHX). Moreover, mitogen-activated protein
      kinase (MEK) /extracellular-signal-regulated kinase (ERK) pathway inhibitors;
      U0126 (1.4-diamino-2, 3-dicyano-1, 4-bis [2-amino-phenylthio] butadiene) and
      PD98059 (2'-Amino-3'-methoxyflavone) inhibited inducible Glvr-2 mRNA expression,
      but p38 MEK inhibitor SB203580 [4-(4'-fluorophenyl)-2-(4'-methyl-sulfinylphenyl)
      5-(4'pyridyl) imidazole] did not inhibit the induction of Glvr-2 mRNA expression,
      suggesting that extracellular Pi regulates de novo protein synthesis and MEK/ERK
      activity in rat bone marrow stromal cells, and through these, induction of Glvr-2
      mRNA. Although Pi also induced osteopontin mRNA expression in rat bone marrow
      stromal cells but not in ROB-C26 and NRK cells, changes in cell viability with
      the addition of Pi were similar in both cell types. These data indicate that
      extracellular Pi regulates Glvr-2 mRNA expression, provide insights into possible
      mechanisms whereby Pi may regulate protein phosphorylation, and suggest a
      potential role for the Pi transporter in rat bone marrow stromal cells.

PMID- 14584043
TI  - cPLA2 activator peptide, PLAP, increases arachidonic acid release and apoptosis
      of vascular smooth muscle cells.
AB  - Apoptosis of vascular smooth muscle cells (VSMCs) has recently drawn a lot of
      interest in various laboratories due to its importance in atherogenesis. We have
      shown previously that nitric-oxide (NO) can induce apoptosis of VSMCs and that
      the NO-induced apoptosis is accompanied by an increase in arachidonic acid
      release via cytoplasmic Ca(2+)-dependent phospholipase A(2) (cPLA(2)). We have
      demonstrated here that NO-induced activation of cPLA(2) leading to increased
      arachidonic acid release can be mimicked via direct activation of cPLA(2) with a
      cPLA(2) activator peptide, PLAP. The PLAP induced arachidonic acid release and
      apoptosis is inhibitable by a cPLA(2)-specific inhibitor, AACOCF(3), indicating
      the direct involvement of cPLA(2). In this study, activation of cPLA(2) appears
      to be preceded by activation and binding by PLAP indicating that the cPLA(2)
      functions are mediated via PLAP.

PMID- 14584044
TI  - Opposing effect of angiopoietin-1 on VEGF-mediated disruption of endothelial cell
      cell interactions requires activation of PKC beta.
AB  - Angiopoietin-1 (Ang1) and vascular endothelial growth factor (VEGF) cooperate in
      migration and survival of endothelial cells by activation of phosphatidylinositol
      3 (PI-3) kinase and mitogen activating protein (MAP) kinase pathways. However,
      Ang1 opposes the effect of VEGF on vascular permeability. We found that Ang1 also
      blocks VEGF-mediated diffusion of fluoresin isothiocyanate (FITC)-labeled albumin
      across an endothelial cell monolayer. VEGF-mediated vascular permeability has
      been attributed, in part, to activation of phospholipase A(2) and subsequent
      formation of platelet activating factor. However, Ang1 had no effect on VEGF
      induced activation of phospholipase A(2) or the release of arachidonic acid. VEGF
      mediated permeability was associated with disruption of endothelial cell
      junctional complexes, dissociation of beta-catenin from VE-cadherin, and
      accumulation of beta-catenin in the cytosol. In contrast, Ang1 enhanced the
      interaction of beta-catenin with VE-cadherin and impaired VEGF-mediated
      dissociation of this complex. Ang1 also blocked VEGF-induced translocation of
      protein kinase C (PKC) and beta2 to the membrane, but had no effect on activation
      of PKC alpha. In addition, staurosporine and a PKC beta inhibitor, LY379196,
      blocked VEGF-mediated dissociation of beta-catenin from VE-cadherin, diffusion of
      albumin across the endothelial cell monolayer, and translocation of PKC beta
      isoforms. These data indicate that VEGF-mediated disruption of endothelial cell
      cell interactions requires activation of PKC beta isoforms and that this pathway
      is blocked by Ang1.

PMID- 14584045
TI  - EGF mediates protection against Fas-induced apoptosis by depleting and oxidizing
      intracellular GSH stocks.
AB  - Several pieces of evidence have demonstrated the importance of
      reduction/oxidation (redox) signaling in biological processes, including
      sensitivity toward apoptosis. In parallel, it was recently reported that growth
      factors induce the generation of reactive oxygen species (ROS). Therefore, we
      tested the hypothesis that the anti-apoptotic effect of epidermal growth factor
      (EGF) was mediated by changes in the redox state of hepatocytes through changes
      in GSH stocks. Isolated mouse hepatocytes were cultured and exposed to anti-Fas
      stimulation in order to induce apoptosis. Cell death by apoptosis was assessed by
      Hoechst 33258 staining and by measuring caspase-3 proteolysis activity. Cell
      treatment with EGF significantly decreased total (GSx) and reduced (GSH)
      glutathione levels in the presence and the absence of anti-Fas. Furthermore,
      glutathione reductase activity was lower in EGF-treated cultures (by 28%) as
      compared to untreated cultures which lead to a significant decline in GSH/GSx
      ratio. These effects were found to be EGF-receptor tyrosine kinase activity
      dependent. Co-stimulation of cells with anti-Fas and EGF attenuated caspase-3
      activation and cell death by apoptosis by 70%. GSH monoethylester (GSHmee)
      significantly attenuated the effect of EGF on GSH and GSH/GSx ratio. It caused an
      increase in caspase-3 activation and in the percentage of apoptotic cells in anti
      Fas + EGF-treated cells, thus resulting in a 53% decline in the protective effect
      of EGF. In conclusion, EGF induces a significant and specific depletion and
      oxidization of intracellular GSH, paralleled by a protection against Fas-induced
      apoptosis. GSH repenishment partly counteracted these effects suggesting that GSH
      depletion contributed to the protective effect of EGF against caspase-3
      activation and cell death by apoptosis.

PMID- 14584046
TI  - Critical protein domains and amino acid residues for gating the KIR6.2 channel by
      intracellular ATP.
AB  - K(ATP) channels couple intermediary metabolism to cellular excitability. Such a
      property relies on the inherent ATP-sensing mechanism known to be located in the
      Kir6 subunit. However, the molecular basis for the ATP sensitivity remains
      unclear. Here we showed evidence for protein domains and amino acid residues
      essential for the channel gating by intracellular ATP. Chimerical channels were
      constructed using protein domains of Kir6.2 and Kir1.1, expressed in HEK293
      cells, and studied in inside-out patches. The N and C termini, although
      important, were inadequate for channel gating by intracellular ATP. Full ATP
      sensitivity also required M1 and M2 helices. Cytosolic portions of the M1 and M2
      sequences were crucial, in which six amino acid residues were identified, i.e.,
      Thr76, Met77, Ala161, Iso162, Leu164, and Cys166. Site-specific mutation of any
      of them reduced the ATP sensitivity. Construction of these residues together with
      the N/C termini produced ATP sensitivity identical to the wild-type channels. The
      requirement for specific membrane helices suggests that the Kir6.2 gating by ATP
      is not shared by even two closest relatives in the K(+) channel family, although
      the general gating mechanisms involving membrane helices appear to be conserved
      in all K(+) channels.

PMID- 14584047
TI  - Elevated interleukin-9 receptor expression and response to interleukins-9 and -7
      in thymocytes during radiation-induced T-cell lymphomagenesis in B6C3F1 mice.
AB  - Dysregulation of cytokine receptor expression and responsiveness to cytokines is
      hypothesized to play an important role in the development and expansion of
      preneoplastic cells or progression of neoplastic cells during the early and late
      stages of leukemogenesis. To determine the crucial changes in initiated cells
      that confer significant growth during the early stage of radiation-induced
      lymphomagenesis, we examined both the expression of receptors for thymus-derived
      cytokines and thymocyte response to cytokines before the onset of T cell
      lymphomas in B6C3F1 mice after split-dose irradiation. After irradiation, thymic
      T cell subsets underwent delayed regeneration consisting of two phases as
      determined by receptor expression. The first phase occurred within 1 week post
      irradiation and was accompanied by transient expansion of T cell subsets strongly
      expressing receptor genes for IL-1, IL-2, IL-6, IL-7, IL-15, and TNF alpha. The
      second phase occurred 12 weeks after irradiation and was characterized by
      increased expression of IL-9R alpha. Thymocytes from non-irradiated control mice
      were unresponsive to IL-9. However, IL-9 acted synergistically with IL-7 and PHA
      to stimulate the proliferation of irradiated cells during the second post
      irradiation phase. Moreover, these cells showed hyper-responsiveness to IL-7 or
      PHA alone compared to age-matched non-irradiated control thymocytes. These
      results suggest that the unusual expression of IL-9 receptors and/or increased
      responsiveness of thymocytes to cytokines are key processes in the development of
      radiation-induced T cell lymphomas.

PMID- 14584048
TI  - Effects of peripheral benzodiazepine receptor ligands on proliferation and
      differentiation of human mesenchymal stem cells.
AB  - The peripheral benzodiazepine receptor (PBR) has been known to have many
      functions such as a role in cell proliferation, cell differentiation,
      steroidogenesis, calcium flow, cellular respiration, cellular immunity,
      malignancy, and apoptosis. However, the presence of PBR has not been examined in
      mesenchymal stem cells. In this study, we demonstrated the expression of PBR in
      human bone marrow stromal cells (hBMSCs) and human adipose stromal cells (hATSCs)
      by RT-PCR and immunocytochemistry. To determine the roles of PBR in cellular
      functions of human mesenchymal stem cells (hMSCs), effects of diazepam, PK11195,
      and Ro5-4864 were examined. Adipose differentiation of hMSCs was decreased by
      high concentration of PBR ligands (50 microM), whereas it was increased by low
      concentrations of PBR ligands (<10 microM). PBR ligands showed a biphasic effect
      on glycerol-3-phosphate dehydrogenase (GPDH) activity. High concentration of PBR
      ligands (from 25 to 75 microM) inhibited proliferation of hMSCs. However,
      clonazepam, which does not have an affinity to PBR, did not affect adipose
      differentiation and proliferation of hMSCs. The PBR ligands did not induce cell
      death in hMSCs. PK11195 (50 microM) and Ro5-5864 (50 microM) induced cell cycle
      arrest in the G(2)/M phase. These results indicate that PBR ligands play roles in
      adipose differentiation and proliferation of hMSCs.

PMID- 14584049
TI  - Resistance to UV-induced apoptosis in human keratinocytes during accelerated
      senescence is associated with functional inactivation of p53.
AB  - Compared to proliferating keratinocytes (KCs), growth-arrested KCs are relatively
      resistant to UV-light induced apoptosis. When KCs undergo confluency, or
      following exposure to anti-proliferative agents such as IFN-gamma plus a phorbol
      ester-12-O-tetradecanoylyphorbol-13-acetate (TPA), they convert from a
      proliferative to a nonproliferative state resembling senescence. Since p53
      regulates UV-induced apoptosis of KCs, this report further characterizes p53 half
      life, post-translational modifications, and transcriptional activity using
      cultured human KCs and living epidermal equivalents. The half-life of p53 in KCs
      was longer than fibroblasts (greater than approximately 3 h vs. 30 min). Exposure
      of proliferating KCs to UV-light induces post-translational modifications of p53
      including acetylation of lysine-382 residues. By contrast, KCs undergoing
      irreversible growth arrest following confluency, or exposure to IFN-gamma plus
      TPA, were resistant to UV-induced apoptosis, and failed to undergo the
      acetylation modification of p53. Exposure of KCs to IFN-gamma plus TPA reduced
      total cellular p53 levels and reduced the transcriptional activity of p53.
      Addition of Trichostatin A (TSA), an inhibitor of de-acetylation, increased
      acetylation of lysine-382 in confluent KCs, thereby enhancing susceptibility of
      confluent cultures to UV-induced apoptosis. Pre-treatment of epidermal
      equivalents with IFN-gamma plus TPA also blocked UV-light induced increase in p53
      levels, and reduced apoptosis. In conclusion, these studies demonstrate that
      growth arrested KCs may resist UV-light induced apoptosis by inactivating the pro
      apoptotic function of p53.

PMID- 14584050
TI  - Non-hematopoietic human bone marrow contains long-lasting, pluripotential
      mesenchymal stem cells.
AB  - Mesenchymal stem cells (MSC) are considered as potential agents for
      reconstructive and gene-targeting therapies since they differentiate into various
      cell-lineages, exhibit an extended survival once injected into a host, and can
      easily be transfected with engineered DNA. MSC are essentially isolated from
      hematopoietic bone marrow (BM), a process that is rather invasive and may raise
      ethical concerns. In an attempt to find an alternative source, we evaluated
      whether non-hematopoietic (nh)BM recovered from femoral heads of patients
      undergoing hip arthroplasty contained MSC. Ex vivo, 99% of nhBM cells were
      CD45(+) leukocytes. After culture, leukocytes were replaced by a homogeneous
      layer of adherent CD45(-) CD14(-) CD34(-) CD11b(-) CD90(+) HLA-ABC(+) cells.
      Culture doubling time (mean = 4 days, range 1.6-6.7 days) was not correlated with
      patient age (27-81 years, n = 16). Amplified cultures supported long-term
      hematopoiesis, and could be differentiated in vitro into adipocytes and
      chondrocytes. Moreover, a small fraction of nhBM cells spontaneously expressed
      MyoD1 and formed myotubes, suggesting that myogenic differentiation also
      occurred. nhBM contained clonogenic cells whose frequency (1/13,000), doubling
      time (2.1 days), and maximal amplification (up to 10(6)-fold) were not age
      related. All 14 clones analyzed (from five patients, ages 27-78 years)
      differentiated into at least one mesenchymal lineage, and 66% were bipotential (n
      = 8/12), or tripotential (n = 2/3). In conclusion, nhBM contains pluripotential
      mesenchymal progenitors which are similar to hematopoietic BM-derived MSC, and
      whose biological functions are not altered by aging. Furthermore, if MSC-based
      therapies hold their promises, nhBM may become the source of choice for
      responding to the increasing demand for MSC.

PMID- 14584051
TI  - Gonadotropin and steroid hormones stimulate proliferation of the rat ovarian
      surface epithelium.
AB  - The ovarian surface epithelium (OSE) is a single layer of flattened or cuboidal
      cells covering the ovary. Ninety percent of all human ovarian malignancies arise
      from this layer of cells. Incessant ovulation, hyperovulation induced by
      infertility treatment, and hormone replacement therapy have been suggested as
      risk factors for ovarian cancer. In this study, two groups of rats, with and
      without surgically induced injury to the ovary, were treated with 17beta
      estradiol, pregnant mare's serum gonadotropin (PMSG), human chorionic
      gonadotropin (hCG), or the combination PMSG/hCG, and the proliferative response
      of the OSE cells was measured using bromodeoxyuridne (BrdU) and (3)H-thymidine.
      All hormones, alone or in combination with ovarian surgery, were found to
      increase significantly the rate of proliferation of the rat OSE. These data
      demonstrate that hormones associated with infertility treatments and hormone
      replacement therapy, as well as injury- or ovulation-induced rupture of the
      ovarian surface, stimulate the rat OSE, and hence could have a role in the
      development of ovarian cancer via proliferation-associated mutagenesis, or
      alternatively, by promoting the rapid selection of OSE cells with accumulated
      mutations.

PMID- 14584052
TI  - Gingival and dermal fibroblasts produce interleukin-1 beta converting enzyme and
      interleukin-1 beta but not interleukin-18 even after stimulation with
      lipopolysaccharide.
AB  - Epithelial cells play a critical role in periodontal disease through the
      secretion of pro-inflammatory cytokines such as interleukin-1 beta (IL-1 beta)
      and interleukin-18 (IL-18). However, the role played by fibroblasts is still
      unclear. The rationale of this study was to throw light on the role of gingival
      fibroblasts in periodontal disease. We thus investigated the expression of IL-1
      beta, IL-18, and ICE mRNA and the secretion of the corresponding proteins by
      human normal gingival fibroblasts before and after stimulation with
      lipopolysaccharide (LPS) from Porphyromonas gingivalis and Escherichia coli. IL-1
      beta, IL-18, and ICE mRNA expression was evaluated by RT-PCR. Proteins were
      analyzed by Western blot and ELISA. We demonstrated that gingival fibroblasts
      expressed ICE mRNA. Basal expression of ICE was modulated following cell
      stimulation with lipopolysaccharide (5 mug/ml). However, gingival fibroblasts
      expressed low levels of IL-1 beta mRNA. The expression was potentiated by LPS.
      The expression of IL-1 beta mRNA was followed by the secretion of IL-1 beta but
      not IL-18 protein. Our study suggests that fibroblasts may be involved in the
      defense against infections via an IL-1 beta-mediated but not an IL-18-mediated
      mechanism.

PMID- 14584053
TI  - Cationic polyelectrolyte hydrogel fosters fibroblast spreading, proliferation,
      and extracellular matrix production: Implications for tissue engineering.
AB  - Fibrous encapsulation is known to occur to many prosthetic implants and is
      thought to be due to the cells not adhering adequately to the surface. For
      developing new materials able to enhance cellular adhesion by mimicking
      extracellular matrix components, polyelectrolyte polymers, characterized by
      tunable surface charges, have been proposed. Here we demonstrate that panoply of
      cell functions over a two-dimensional substratum is influenced by surface charge.
      We have at first generated structurally related polyelectrolyte substrata varying
      in their positive surface charge amount and subsequently evaluated a variety of
      behaviors of human primary fibroblasts seeded on these polymers. The proportion
      of adherent, spreading, and proliferating cells was increased significantly on
      cationic hydrophilic surfaces when compared with the neutral base surface. The
      extent of cell spreading correlated with cytoskeleton organization as assessed
      using immunofluorescence techniques. In the key experiment, the presence of
      cationic charges on cell adhesion-resistant neutral surface increased the
      synthesis of collagen I and III, the release of their metabolites, and the
      expression of their mRNA by fibroblasts. Interestingly, the scarce collagen
      deposits on neutral polymer consisted, for the most part, of collagen I while
      collagen III was present only in traces probably due to the secretion of
      metalloproteinase-2 by non-adherent fibroblasts. Taken together, these results
      show that polyelectrolyte films may promote the attachment of fibroblast cells as
      well as their normal secretory phenotype. Both effects could be potentially
      useful in integrating soft connective tissue to the implant, decreasing the
      chance of its fibrous encapsulation.

PMID- 14584054
TI  - Differentiation-dependent activation of the extracellular fatty acid binding
      protein (Ex-FABP) gene during chondrogenesis.
AB  - Chicken hypertrophic chondrocytes secrete the extracellular fatty acid binding
      protein (Ex-FABP), a lipocalin not expressed by their undifferentiated
      precursors. Genomic clones coding for the full protein are here structurally and
      functionally analyzed. We first determined that the promoter sequence markedly
      differs from that reported for the homologous p20K, and we confirmed by genomic
      DNA Southern analysis the exactness of our sequence. This is of relevance since
      we have identified another lipocalin gene within the region of discrepancy,
      indicating thereby the existence of a lipocalin cluster within the same
      chromosomal locus. By transient transfections with 5'-deletions and the
      chloramphenicol acetyl transferase (CAT) reporter gene, the region between nt 
      926 and nt -629 was shown to be strongly active, specifically in hypertrophic
      chondrocytes and not in dedifferentiated cells. Responsive elements for several
      potential transcription factors lay within this sequence. Among those, activating
      protein-1 (AP-1) was shown to be involved in the regulation of the Ex-FABP gene
      during chondrocyte differentiation, as indicated by electrophoretic mobility
      shift assay, AP-1 site mutagenesis and functional interference assays.

PMID- 14584055
TI  - Osteopontin modulates CD44-dependent chemotaxis of peritoneal macrophages through
      G-protein-coupled receptors: evidence of a role for an intracellular form of
      osteopontin.
AB  - Expression of osteopontin (OPN) by activated T-cells and macrophages is required
      for the development of cell-mediated inflammatory responses. Acting through
      integrin alpha(v)beta(3) and CD44 receptors, OPN can promote chemoattraction and
      pro-inflammatory cytokine expression by macrophages. In this study, we have used
      peritoneal macrophages from OPN-/, CD44-/-, and WT mice to study the relationship
      between OPN and CD44 in macrophage migration. Using confocal microscopy, we show
      that OPN co-distributes with CD44 inside macrophages at cell edges and in cell
      processes in a mutually dependent manner. The existence of an intracellular form
      of OPN is supported by pulse-chase studies in which a thrombin-sensitive,
      phosphorylated protein immunoprecipitated with OPN antibodies is retained inside
      macrophages. In OPN-/- and CD44-/- macrophages, the absence of CD44 and OPN,
      respectively, is associated with the formation of fewer cell processes, reduced
      cell fusion required to form functional multinucleated osteoclasts in the
      presence of CSF-1 and RANKL, and impaired chemotaxis. Whereas the chemotaxis of
      CD44-/- cells to various chemoattractants is almost completely abrogated, a
      differential effect is seen with the OPN-/- cells. Thus, OPN-/- cells migrate
      normally towards CSF-1 but not towards fMLP and MCP-1, which signal through G
      protein coupled receptors (GPCRs). That the GPCR-mediated migration is dependent
      upon the level of cell-surface CD44 is indicated by the reduced cell-surface
      expression of CD44 in OPN-/- cells and a comparable impairment in the chemotaxis
      of CD44+/- cells. Although chemotaxis of OPN-/- cells could be rescued by an OPN
      substratum, or by addition of high levels of OPN in solution, no response is
      evident with physiological levels of OPN, indicating a requirement for the CD44
      associated intracellular OPN in CD44 cell-surface expression. These studies
      indicate, therefore, that the level of cell surface CD44 is critical for GPCR
      mediated chemotaxis by peritoneal macrophages and suggest that a novel
      intracellular form of OPN may modulate CD44 activities involved in these
      processes.

PMID- 14584057
TI  - Adjuvant aromatase inhibitors: are we there yet?

PMID- 14584058
TI  - Nutritional strategies for breast cancer prevention: what have we learned and
      where do we go from here?

PMID- 14584059
TI  - Cancer-related fatigue: evolving concepts in evaluation and treatment.
AB  - BACKGROUND: Although fatigue is one of the most common complaints of patients
      with cancer, it went unrecognized or overlooked for many years, until clinicians
      achieved better control over the more acute symptoms of nausea, emesis, and pain.
      A number of treatment-related and disease-related factors may contribute to the
      development of fatigue, but its physiologic basis remains poorly understood, and
      many proposed interventions have not been studied systematically. The lack of a
      standard of care for the assessment or treatment of fatigue in patients with
      cancer has limited research in this field. A critical appraisal of these issues
      is presented in this review. METHODS: The published literature was reviewed for
      definition, prevalence, causes, and means of managing cancer-related fatigue
      (CRF). RESULTS: Fatigue was reportedly present at the time of diagnosis in
      approximately 50-75% of cancer patients. The prevalence of CRF increased to 80
      96% in patients undergoing chemotherapy and to 60-93% in patients receiving
      radiotherapy. Two tested interventions that showed consistent effects to
      alleviate CRF were treatment of cancer-related anemia with erythropoietin agents
      (recombinant human erythropoietin and darbepotin alpha) and aerobic exercise.
      CONCLUSIONS: Several lines of research are needed to bridge the specific gaps in
      the current knowledge of CRF. These involve the pathophysiology of the symptom,
      the validation of diagnostic criteria, and specific therapeutic interventions.
      Current practice guidelines are based on a combination of research and expert
      clinical judgment and should be used to guide care with the expectation that they
      will evolve to incorporate the results of studies currently underway.

PMID- 14584060
TI  - Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for
      adjuvant treatment of postmenopausal women with early-stage breast cancer:
      results of the ATAC (Arimidex, Tamoxifen Alone or in Combination) trial efficacy
      and safety update analyses.
AB  - BACKGROUND: The first analysis of the ATAC (Arimidex, Tamoxifen Alone or in
      Combination) trial (median follow-up, 33 months) demonstrated that in adjuvant
      endocrine therapy for postmenopausal patients with early-stage breast cancer,
      anastrozole was superior to tamoxifen in terms of disease-free survival (DFS),
      time to recurrence (TTR), and incidence of contralateral breast cancer (CLBC). In
      the current article, the results of the first efficacy update, based on a median
      follow-up period of 47 months, are reported along with the results of an updated
      safety analysis, performed 7 months after the first analysis (median duration of
      treatment, 36.9 months). METHODS: DFS, TTR, CLBC incidence, and safety were
      assessed in the same patient group as in the first analysis of the ATAC trial.
      RESULTS: DFS estimates at 4 years remained significantly more favorable (86.9%
      vs. 84.5%, respectively) for patients receiving anastrozole compared with those
      receiving tamoxifen (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.76
      0.99; P = 0.03). The benefit generated by anastrozole in terms of DFS was even
      greater in patients with hormone receptor-positive tumors (HR, 0.82; 95% CI, 0.70
      0.96; P = 0.014). The HR for TTR also indicated a significant benefit for
      patients receiving anastrozole compared with those receiving tamoxifen (HR, 0.83;
      95% CI, 0.71-0.96; P = 0.015), with additional benefit for patients with hormone
      receptor-positive tumors (HR, 0.78; 95% CI, 0.65-0.93; P = 0.007). CLBC incidence
      data also continued to favor anastrozole (odds ratio [OR], 0.62; 95% CI, 0.38
      1.02; P = 0.062), and statistical significance was achieved in the hormone
      receptor-positive subgroup (OR, 0.56; 95% CI, 0.32-0.98; P = 0.042). The updated
      safety analysis also confirmed the findings of the first analysis, in that
      endometrial cancer (P = 0.007), vaginal bleeding and discharge (P < 0.001 for
      both), cerebrovascular events (P < 0.001), venous thromboembolic events (P <
      0.001), and hot flashes (P < 0.001) all occurred less frequently in the
      anastrozole group, whereas musculoskeletal disorders and fractures (P < 0.001 for
      both) continued to occur less frequently in the tamoxifen group. These results
      indicated that the safety profile of anastrozole remained consistent.
      CONCLUSIONS: After an additional follow-up period, anastrozole continues to show
      superior efficacy, which is most apparent in the clinically relevant hormone
      receptor-positive population. Furthermore, anastrozole has numerous noteworthy
      advantages in terms of tolerability compared with tamoxifen. These findings
      suggest that the benefits of anastrozole are likely to be maintained in the long
      term and provide further support for the status of anastrozole as a valid
      treatment option for postmenopausal women with hormone-sensitive early-stage
      breast cancer.

PMID- 14584061
TI  - Increased expression of matrix metalloproteinase-2 and tissue inhibitor of
      metalloproteinase-2 is correlated with poor prognostic variables in patients with
      thymic epithelial tumors.
AB  - BACKGROUND: A distinction between noninvasive, invasive, and metastatic thymoma
      on the basis of the cytologic features is difficult. The current study
      investigated whether the expression of MMP and TIMP was correlated with tumor
      invasiveness and prognosis in patients with thymoma. METHODS: Tumor tissue
      samples were obtained from 42 patients with thymic epithelial tumors between 1974
      and 2001 at Tokushima University Hospital. Three-micrometer-thick, formalin
      fixed, paraffin-embedded tissue sections were immunostained using specific
      antibodies against MMP-2, MMP-9, TIMP-1, and TIMP-2. RESULTS: MMP-2 expression
      was detected in 30 tumors (71%), and TIMP-2 expression was detected in 31 tumors
      (74%). MMP-9 expression was detected in 22 of 36 tumors (61%), and TIMP-1
      expression was detected in only 7 tumors (19%). MMP-2 and TIMP-2 expression
      levels were very low (10% and 0%, respectively) in noninvasive tumors but were
      very high (91% and 97%, respectively) in invasive tumors. In thymic epithelial
      tumors, the more progressive the clinical stage of tumor, the higher the strongly
      positive rate of MMP-2 and TIMP-2 expression. There was no correlation between
      positivity for MMP-9 and stage. Twenty-five percent of Type AB thymomas and 50%
      of Type B1 thymomas expressed MMP-2 and TIMP-2. Most of Type A, Type B2, Type B3,
      and Type C thymomas expressed MMP-2 and TIMP-2. There were significant
      differences in disease-free survival at 5 years between patients without and with
      MMP-2 expression (91% vs. 55%, respectively) and patients without and with TIMP-2
      expression (100% vs. 53%, respectively). CONCLUSIONS: MMP-2 and TIMP-2 are key
      enzymes for invasiveness of thymic epithelial tumors. The expression of these
      proteins can predict a poor outcome in patients with thymoma.

PMID- 14584062
TI  - Characteristics of primary care physicians and their practices associated with
      mammography rates for older women.
AB  - BACKGROUND: Mammography screening rates are below national recommendations for
      older women. Understanding the relation between the characteristics of primary
      care physicians (PCPs) and mammography rates for older women can help to target
      screening improvement efforts. METHODS: Subjects were 2527 PCPs practicing in
      Michigan between 1997 and 1998. A cross-sectional design used Medicare data to
      identify women age 68 years or older in 1998 whom PCPs treated in 1997-1998 and
      to determine whether these women had a mammogram between 1996 and 1998. Eligible
      women were Medicare beneficiaries age 65 years or older by 1996, residing in
      Michigan from 1996 to 1998, without specified comorbidities likely to affect
      decisions regarding mammography. Correlations and multiple regressions examined
      the relation between this score and characteristics of both PCPs and their
      practice populations of older women. RESULTS: Mammography rates across
      physicians' practices ranged from 3-100% (mean = 59%, standard deviation = 17%).
      Five predictors accounted for 55% of the variance in mammography rates across
      practices. Higher mammography rates were found to be independently related to
      physicians who have: a lower mean age for female Medicare patients, a higher mean
      number of physicians billing for patients' care, a lower mean number of inpatient
      admissions, obstetrics/gynecology practices, and a higher mean education level in
      patient's zip code (beta weights >/= 0.25, P < 0.0001). CONCLUSIONS: PCPs vary
      substantially with regard to mammography rates for older women. Mammography rates
      vary more with the population of patients in physicians' practices than with
      commonly measured personal characteristics of physicians. Mammography rates
      should be adjusted for patient population to target individual PCPs with low
      mammography rates for interventions.

PMID- 14584063
TI  - Molecular genetic alterations in the laser-capture-microdissected stroma adjacent
      to bladder carcinoma.
AB  - BACKGROUND: Urothelial carcinoma commonly manifested loss of heterozygosity (LOH)
      at different regions of chromosomes 17p, 3p, and 9q. Recent studies suggested
      that bladder stromal cells may be implicated in the growth and progression of
      urothelial carcinoma. To better understand the genetic alterations in the stromal
      cells in patients with bladder carcinoma, the authors evaluated the prevalence of
      allelic loss at three microsatellite polymorphic markers on chromosomes 17p13
      (TP53), 3p25-26 (D3S3050), and 9q32-33 (D9S177). In addition, the pattern of X
      chromosome inactivation of the stromal cells was evaluated by analyzing the DNA
      methylation pattern at a polymorphic site on the androgen receptor gene. METHODS:
      The authors studied 18 female patients who underwent either transurethral
      resection (n = 2) or radical cystectomy (n = 16) for high-grade muscle-invasive
      urothelial carcinoma of the urinary bladder. Genomic DNA samples from the stromal
      cells immediately adjacent to the tumor and the tumor itself were prepared from
      formalin-fixed, paraffin-processed tissues using laser-assisted microdissection
      and LOH was determined. RESULTS: The stromal cells showed a high frequency of LOH
      on chromosomes 17p13 (29%), 3p25-26 (61%), and 9q32-33 (47%) with no clear
      concordance with the adjacent tumor cells. Fourteen specimens (78%) showed LOH in
      the stroma in at least 1 of 3 markers examined. Nonrandom X-chromosome
      inactivation was frequent in the stromal cells (50% of informative specimens).
      CONCLUSIONS: The current study revealed that some of the genetic changes that
      commonly occur with invasive urothelial carcinoma were frequently found in the
      adjacent stroma and suggested that the stroma of urothelial carcinoma may play an
      important role in bladder carcinogenesis.

PMID- 14584064
TI  - Vinblastine and estramustine phosphate in metastatic renal cell carcinoma: a
      phase II trial of the Fox Chase Network.
AB  - BACKGROUND: It is well known that metastatic renal cell carcinoma (RCC) exhibits
      constitutive resistance to chemotherapeutic agents. Antimicrotubule agents such
      as vinblastine are associated with low but reproducible response rates
      (approximately 12%) in patients with RCC. Estramustine has been shown to
      potentiate the antimicrotubule effects of vinblastine. The authors sought to
      increase the activity of vinblastine in RCC through the addition of estramustine.
      METHODS: Twenty-one patients with metastatic RCC not previously treated with
      chemotherapy received oral estramustine phosphate, 600 mg/m(2), on Days 1, 2, and
      3 weekly for 6 weeks, and intravenous vinblastine, 4 mg/m(2) on Day 2 weekly for
      6 weeks, repeated every 8 weeks. Twenty-one patients received 31 cycles of
      therapy. RESULTS: Two patients experienced Grade 3 and 4 hematologic toxicity,
      and three patients had Grade 3 nonhematologic toxicity consisting of neurologic
      toxicity, hepatic toxicity, or angioneurotic edema. One patient had a partial
      response with decreased liver metastases for 48 weeks; 9 patients had stable
      disease, for a median duration of 14 weeks (range, 11-31 weeks); and 11 patients
      demonstrated disease progression. The median overall time to progression was 8
      weeks and the median overall survival period was 24 weeks. CONCLUSIONS: Although
      well tolerated, the combination of oral estramustine phosphate with vinblastine
      administered on this schedule had minimal activity in patients with metastatic
      RCC.

PMID- 14584065
TI  - Clinical experience with intravenous estramustine phosphate, paclitaxel, and
      carboplatin in patients with castrate, metastatic prostate adenocarcinoma.
AB  - BACKGROUND: The combination of paclitaxel, oral estramustine phosphate (EMP), and
      carboplatin (TEC) has shown antitumor activity in patients with castrate,
      metastatic prostate carcinoma. To improve the therapeutic efficacy and reduce the
      toxicity of TEC, the authors substituted intravenous (i.v.) EMP for oral EMP
      based on single-agent studies demonstrating an improved safety profile with i.v.
      EMP. METHODS: Patients with progressive, castrate, metastatic prostate carcinoma
      were treated with up to 6 4-week cycles of i.v. EMP (500-1500 mg/m(2) per week),
      paclitaxel (100 mg/m(2) per week), and carboplatin (target area under the curve =
      6 mg/mL every 4 weeks). RESULTS: Thirty patients were treated in 6 dose cohorts.
      Deep venous thrombosis occurred in 5 of 30 patients (17%). Other common Grade 3/4
      (according to National Cancer Institute Common Toxicity Criteria) toxicities
      included hepatic toxicity (23%) and leukopenia (24%). Posttherapy prostate
      specific antigen declines > 50% were seen in 18 of 30 patients (60%), and
      declines > 80% were seen in 15 of 30 patients (50%). Eleven of 17 patients (65%)
      with measurable soft tissue disease achieved a partial response. Four of 27
      patients (15%) with osseous metastases demonstrated improvement on bone scan.
      CONCLUSIONS: Intravenous EMP was administered safely with paclitaxel and
      carboplatin and produced clinical outcomes similar to the outcomes achieved with
      the TEC regimen. Substitution of i.v. EMP for the oral formulation was found to
      result in a lower incidence of severe nausea but increased hepatic toxicity.

PMID- 14584067
TI  - Docetaxel and ketoconazole in advanced hormone-refractory prostate carcinoma: a
      phase I and pharmacokinetic study.
AB  - BACKGROUND: Docetaxel has significant single-agent activity in patients with
      prostate carcinoma, and ketoconazole has activity as a second-line hormonal
      agent. In vitro, ketoconazole exhibits synergy with several chemotherapeutic
      agents. A potential drug interaction exists, however, because both docetaxel and
      ketoconazole are metabolized hepatically by the cytochrome p450 system (CYP3A4).
      The authors performed a Phase I study and a pharmacokinetic study evaluating the
      both tolerability of a docetaxel/ketoconazole combination as well as this
      potential drug interaction. METHODS: For all initial patients, docetaxel was
      administered intravenously at a dose of 55 mg/m(2) over 1 hour every 21 days.
      Starting on Day 8 after their first docetaxel dose, cohorts of at least 3-5 new
      patients were enrolled to receive escalating doses of ketoconazole. When the
      maximally tolerated dose (MTD) of ketoconazole was reached, the subsequent cohort
      of patients received an escalating dose of docetaxel. Pharmacokinetic studies
      were performed after docetaxel infusions on Day 1 (prior to ketoconazole) and Day
      22 (after starting ketoconazole). RESULTS: Twenty-six patients were enrolled and
      completed at least 2 cycles of treatment. The MTD was ketoconazole 400 mg twice
      daily and docetaxel 55 mg/m(2). Dose-limiting toxicities included neutropenia and
      fatigue. Ketoconazole did not cause a consistent effect on docetaxel
      pharmacokinetics, although there was significant intrapatient and interpatient
      variability in serum levels. CONCLUSIONS: The recommended Phase II dose for this
      combination is ketoconazole 400 mg twice daily and docetaxel 55 mg/m(2) every 21
      days.

PMID- 14584066
TI  - A neurocomputational model for prostate carcinoma detection.
AB  - BACKGROUND: Current guidelines for prostate carcinoma screening rely primarily on
      the digital rectal examination (DRE) and prostate specific antigen (PSA). Well
      described patient risk factors for prostate carcinoma also include age,
      ethnicity, family history, and complexed PSA. However, due to the nonlinear
      relation of each of these variables with prostate carcinoma, it is difficult to
      predict reliably each patient's risk based on linear univariate analysis. The
      authors investigated a neural network to model the risk of prostate carcinoma by
      seven readily available clinical features. METHODS: The database for the current
      study comprised 3268 men recently evaluated for the early detection of prostate
      carcinoma. The seven clinical features evaluated included age, race, family
      history, International Prostate Symptom Score (IPSS), DRE, and total and
      complexed PSA. Three hundred forty-eight subjects in the dataset included men
      with determined prostate biopsy outcomes and for whom at least 6 of 7 features
      were available. The dataset was divided randomly into a training set (60%) and a
      test set (40%), with n1/n2 cross-validation used to evaluate model accuracy, and
      was modeled with linear and quadratic discriminant function analysis and a neural
      computational system. After a model with acceptable goodness of fit was achieved,
      reverse regression analysis using Wilks's generalized likelihood ratio test was
      performed to evaluate the statistical significance of each input variable.
      RESULTS: The receiving operating characteristic (ROC) area for the neural
      computational system in the test set was 0.825, whereas total PSA and complexed
      PSA alone had ROC areas of 0.678 and 0.697, respectively. The ROC area of
      logistic regression in the test set was 0.510, linear discriminant function
      analysis was 0.674, and quadratic discriminant function analysis was 0.011. All
      were significantly less than the ROC area of the neural computational model (all
      Ps < 0.002). Reverse regression based on Wilks's generalized likelihood ratio
      test demonstrated each input feature to be highly significant to the model (all
      Ps << 0.000001). CONCLUSIONS: The authors modeled a combination of well described
      patient risk factors for prostate carcinoma using a neural computational system
      with acceptable goodness of fit. They demonstrated that each of the seven
      variates on which the model was based was critically significant to model
      performance. The authors presented this model for clinical use and suggested that
      clinicians use it in deciding to perform prostate biopsy.

PMID- 14584068
TI  - A phase II study of gemcitabine and docetaxel therapy in patients with advanced
      urothelial carcinoma.
AB  - BACKGROUND: The objectives of the current study were to evaluate the safety and
      efficacy of gemcitabine plus docetaxel in patients with unresectable (Stage T4 or
      >/= N1) metastatic or locally advanced transitional cell carcinoma (TCC) of the
      urothelial tract. METHODS: A total of 27 patients were enrolled in the current
      multisite study, which was performed within the University of California-Los
      Angeles Community Oncology Research Network. The first 10 patients in the study
      received 800 mg/m(2) of gemcitabine intravenously on Days 1, 8, and 15 of a 28
      day treatment cycle. In addition, on Day 1, the first 10 patients received 80
      mg/m(2) of docetaxel intravenously after completion of the gemcitabine infusion.
      Because of dose-limiting toxicity (neutropenia), the initial dose of docetaxel
      was reduced to 60 mg/m(2) for the remaining patients who entered the study (n =
      17 patients). RESULTS: Neutropenia was the most common adverse event that
      occurred in patients at the Grade 3 level (in 10 of 27 patients; 37.0%) and the
      Grade 4 level (in 6 of 27 patients; 22.2%). There were no other adverse events at
      the Grade 4 toxicity level. Twenty-five of 27 patients (92.6%) completed more
      than 1 cycle of combination therapy and were evaluated for antitumor responses.
      The frequency of objective clinical responses was 33.3% (9 of 27 patients).
      Complete responses to therapy were observed in 2 of 27 patients (7.4%), and
      partial responses were observed in 7 of 27 patients (25.9%). The median duration
      of response was 20 weeks (range, 12+ weeks to 152 weeks). The median survival
      duration was 52 weeks (range, 12 weeks to 160+ weeks). Four of 27 patients
      (14.8%) remained alive at the time of the current data analysis. CONCLUSIONS: The
      results of the current study suggested that combination therapy with gemcitabine
      and docetaxel was an effective treatment for patients with unresectable (Stage T4
      or >/= N1) metastatic or locally advanced TCC of the urothelial tract.
      Gemcitabine plus docetaxel appeared to be tolerated well, and treatment-related
      toxicities were limited to hematologic toxicities. Because cisplatin-containing
      regimens are contraindicated for patients with impaired renal function, the
      gemcitabine plus docetaxel combination may prove to be an effective and well
      tolerated treatment option for these patients.

PMID- 14584069
TI  - The effects of a low-fat/high-fiber diet on sex hormone levels and menstrual
      cycling in premenopausal women: a 12-month randomized trial (the diet and hormone
      study).
AB  - BACKGROUND: Reduction of cumulative exposure to endogenous ovarian steroid
      hormones is a postulated method for reducing the risk of carcinoma of the breast
      and other malignancies. Although there are data from trials evaluating the effect
      of low-fat and high-fiber diets on sex hormone levels in premenopausal women, to
      the authors' knowledge none of these trials has combined a relatively large
      number of participants, follow-up of > 2-3 months, parallel controls receiving a
      usual diet, and careful timing of blood sampling within the menstrual cycle.
      METHODS: A total of 213 healthy women, ages 20-40 years, were randomly assigned
      to follow their usual diet or to adopt an isocaloric diet with goals of 20%
      calories as fat, total fiber of 25 g/day, and at least 8 fruit or vegetable
      servings per day. Serum levels of total estradiol (E2), sex hormone-binding
      globulin (SHBG), non-SHBG-bound estradiol (NSBE2), SHBG, and progesterone were
      evaluated during a menstrual cycle at baseline, and at 4 cycles (C4) and 12
      cycles (C12) after the start of the intervention. Serum was collected during each
      test cycle 7-9 days after the detection of an luteinizing hormone peak in the
      urine. One hundred eighty-nine women provided serum at C4 and 176 women at C12.
      RESULTS: Serum E2 decreased by an average of 7.5% or 7.8 pg/mL (95% confidence
      interval [95% CI], -16.0-0.04) at C12 in the intervention group, versus a
      decrease of 0.9% or 0.9 pg/mL (95% CI, -9.5-7.7) in the control group (the P
      value for the difference between the treatment groups was 0.25). Results for
      NSBE2 were very similar to those for total estradiol. There were no material
      effects found to result from intervention with regard to SHBG or progesterone.
      The results did not differ by baseline age, body mass index, or baseline hormone
      level above or below the median, and were not likely to be affected by weight
      change, which amounted to a mean loss of only 0.23 kg in the diet group versus a
      gain of 0.17 kg in the control group. The decrease in serum E2 associated with
      intervention was not greater when subjects were stratified by self-reported
      adherence to the dietary goals. CONCLUSIONS: The results of the current study
      suggest that the effects of this isocaloric low-fat, high-fiber diet pattern on
      circulating ovarian steroids were modest or nonexistent. However, the observed
      7.5% reduction in estradiol could have biologic significance if it persisted over
      many years. Moreover, underestimation of the true dietary effect could have
      occurred because of incomplete adherence to assigned diets. Weight loss and
      weight control through midlife could be a more effective and feasible approach to
      dietary intervention in reducing the risk of breast carcinoma.

PMID- 14584070
TI  - The prognostic impact of cyclin dependent kinase inhibitors p21WAF1, p27Kip1, and
      p16INK4/MTS1 in adenocarcinomas of the uterine cervix: an immunohistochemical
      evaluation of expression patterns in population-based material from 142 patients
      with international federation of gynecology and obstetrics stage I and II
      adenocarcinoma.
AB  - BACKGROUND: The authors assessed the prognostic significance of abnormal cyclin
      dependent kinase inhibitor (CDKI) expression in adenocarcinomas of the uterine
      cervix. METHODS: Population-based, archival material from patients with
      International Federation of Gynecology and Obstetrics (FIGO) Stage I and II
      cervical adenocarcionmas from 2 5-year periods (1976-1980, n = 82 patients; 1986
      1990, n = 142 patients) was examined for expression of p21(WAF1), p27(Kip1), and
      p16(INK4/MTS1) using immunohistochemical techniques. RESULTS: Rates of tumors
      with low levels of nuclear expression of p27 and p16 were lower during the period
      1976-1980 (P < 0.01), suggesting bias due to unbuffered formalin. Analyses that
      were restricted to patients from 1986-1990 showed positive associations between
      all three CDKIs (P < 0.05). Low p16 expression was associated with higher FIGO
      stage (P = 0.01), age older than 55 years (P = 0.01), and deep invasion (P =
      0.003). No significant associations with stage, age, or histopathologic
      parameters were found for p21 or p27. Significant associations with tumor
      differentiation were not seen for any CDKI. Kaplan-Meier plots showed diverging
      survival curves for p21 and p27 expression, but the differences were not
      significant. In multivariate analysis, low p27 expression and high p16 expression
      were strong predictors of a poor prognosis (p27: < 40% nuclear staining; P =
      0.001; hazard ratio, 3.18; p16: < 40% nuclear staining; P < 0.001; hazard ratio,
      0.16). Low p27 expression was of prognostic significance only if it was analyzed
      together with p16 expression. Further evaluation indicated that patients with
      different phenotypic p27/p16 combinations may have different outcomes.
      CONCLUSIONS: Aberrant expression patterns of CDKIs were predictors of prognosis
      for patients with FIGO Stage I or II cervical adenocarcinoma. Analysis of CDKI
      expression in this patient group may prove clinically useful.

PMID- 14584071
TI  - K-ras mutation in tamoxifen-related endometrial polyps.
AB  - BACKGROUND: K-ras mutation is thought to occur at an early stage of neoplastic
      progression in the endometrium. The authors investigated mutations in codon 12 of
      K-ras in tamoxifen (TAM)-related endometrial polyps. METHODS: DNA was extracted
      from 11 frozen endometrial polyps from TAM-treated patients with breast
      carcinoma. Mutations were detected using the mutant allele-specific amplification
      method. The results subsequently were analyzed for correlations with
      immunohistochemical data that were obtained using antibodies against estrogen
      receptors (ERs; alpha and beta forms), progesterone receptors (PRs; A and B
      forms), and Ki-67. RESULTS: Mutations in codon 12 of K-ras were observed in 7 of
      11 TAM-related endometrial polyps. Expression levels of ER-alpha and PR-B were
      high in the glandular epithelium and low in the stroma. PR-A expression was high
      in both the glandular epithelium and the stroma. In the glandular epithelium,
      expression of ER-beta appeared to be lower than expression of ER-alpha. The Ki-67
      index in the glandular epithelium ranged from 2 to 38, whereas the index ranged
      from 0 to 4 in the stroma (P < 0.01). CONCLUSIONS: The incidence of mutations in
      codon 12 of K-ras in TAM-related endometrial polyps (64%) was greater than the
      incidence of these same mutations in sporadic endometrial hyperplasias (4.5-23%).
      High expression levels of ER-alpha, PR-A, and PR-B in the glandular epithelium
      were observed in all polyps, regardless of K-ras codon 12 mutation status and Ki
      67 index. The authors' findings may support the hypothesis that the polyp
      carcinoma sequence partly indicates the development of endometrial carcinoma in
      postmenopausal women who have been treated with TAM.

PMID- 14584072
TI  - The novel serine protease tumor-associated differentially expressed gene-15
      (matriptase/MT-SP1) is highly overexpressed in cervical carcinoma.
AB  - BACKGROUND: Tumor-associated differentially expressed gene-15 (TADG
      15/matriptase/MT-SP1) is a novel transmembrane serine protease involved in
      numerous biologic processes, including activation of growth and angiogenic
      factors and degradation of extracellular matrix components. To assess the value
      of TADG-15 as a possible marker for tumor detection and/or as a target for
      therapeutic intervention, the authors investigated the frequency of expression of
      TADG-15 in human cervical tumors. METHODS: TADG-15 expression was evaluated in 19
      cervical carcinoma cell lines (i.e., 11 primary tumor cell lines and 8
      established cell lines) and in 8 normal cervical keratinocyte control cultures
      using reverse transcriptase-polymerase chain reaction (RT-PCR). In addition, to
      validate gene expression data at the protein level, TADG-15 expression was
      evaluated by immunohistochemistry on paraffin embedded tissue from which all 11
      primary tumor cell lines were established. RESULTS: TADG-15 was expressed at high
      levels in 8 of 11 (73%) primary cervical carcinoma cell lines and in 6 of 8 (75%)
      established cervical carcinoma cell lines by RT-PCR. Expression of TADG-15 was
      found in 6 of 6 (100%) primary squamous cell cervical carcinomas, whereas 2 of 5
      (40%) primary adenocarcinomas expressed TADG-15. In contrast, none of the normal
      cervical keratinocyte control cultures (n = 4) or flash-frozen normal cervical
      biopsy specimens (n = 4) expressed TADG-15. Immunohistochemistry staining of
      paraffin embedded cervical carcinoma specimens confirmed TADG-15 expression in
      tumor cells and its absence on normal cervical epithelial cells. CONCLUSIONS:
      Cervical carcinoma cells expressed high levels of TADG-15, suggesting that this
      protease may play an important role in invasion and metastasis. Because TADG-15
      appears only in abundance in squamous tumor tissue and contains a proteolytic
      cleavage site, suggesting that the TADG-15 protease domain is released, it may
      prove to be a useful diagnostic tool for the early detection of
      recurrent/persistent cervical carcinoma after standard treatment or as a novel
      molecular target for therapy in patients with cervical carcinoma.

PMID- 14584073
TI  - Chromosomal abnormalities in Philadelphia chromosome-negative metaphases
      appearing during imatinib mesylate therapy in patients with Philadelphia
      chromosome-positive chronic myelogenous leukemia in chronic phase.
AB  - BACKGROUND: Anecdotal cases of chromosomal abnormalities in Philadelphia
      chromosome (Ph)-negative metaphases have been reported in patients with chronic
      myelogenous leukemia (CML) in the chronic phase during treatment with interferon
      and, more recently, with imatinib. This phenomenon is different from true clonal
      evolution in that the additional cytogenetic abnormality occurs in Ph-negative
      cells. METHODS: The authors analyzed their experience with 342 patients with CML
      in chronic phase treated with imatinib to investigate the frequency and
      significance of this event. RESULTS: After a median follow-up of 30 months
      (range, 16-35 months), 21 patients (6%; 95% confidence interval, 0.04, 0.09)
      developed 25 chromosomal abnormalities in Ph-negative cells. Thirteen (54%) of
      these abnormalities were seen in 2 or more metaphases. The median time from the
      start of treatment with imatinib to the appearance of the abnormalities was 6
      months (range, 3-22 months). The most common cytogenetic abnormality detected was
      trisomy 8 (33%). Twenty of 21 patients (95%) achieved a major (Ph < 35%)
      cytogenetic response (complete cytogenetic response in 13-62%). After a median
      follow-up of 22 months (range, 4-33 months), all 21 patients were alive, 20 of
      them in chronic phase and in complete hematologic response. None of the patients
      showed features of myelodysplasia. CONCLUSIONS: Cytogenetic abnormalities occur
      in Ph-negative cells in a fraction of patients with CML in chronic phase treated
      with imatinib. With a short follow-up, no clear clinical consequences can be
      identified.

PMID- 14584074
TI  - Pulmonary complications in chronic lymphocytic leukemia.
AB  - BACKGROUND: Although pulmonary complications account for significant morbidity
      and mortality in patients with chronic lymphocytic leukemia (CLL), to the
      authors' knowledge there are sparse data available in published literature. The
      authors evaluated pulmonary complications in patients with CLL and identified
      prognostic variables that predict hospital mortality in these patients. METHODS:
      Clinical data were analyzed retrospectively from patients with CLL who required
      hospitalization for a respiratory illness at a tertiary care institution from
      January 1993 to December 2001. A logistic regression analysis with a backward
      elimination procedure was carried out to determine prognostic variables that
      predict hospital mortality. RESULTS: There were 110 patients who were admitted on
      142 occasions with a pulmonary complication. The median age was 75 years (range,
      43-97 years), and the male:female ratio was 1.7:1.0. Among 142 admissions, 68%
      were high risk according to the Rai criteria, 68% of patients admitted had
      received prior therapy for CLL, and 35% had received treatment within 3 months of
      admission. The most common pulmonary complications were pneumonias (75%),
      malignant pleural effusion/and or lung infiltrate due to CLL (9%), pulmonary
      leukostasis (4%), Richter transformation or nonsmall cell lung carcinoma (3%),
      and upper airway obstruction (2%). Forty-four of 110 patients (40%) died. In
      multivariate analysis, admission absolute neutrophil counts </= 0.5 x 10(9)/L
      (odds ratio, 4.6; 95% confidence interval [95% CI], 1.3-16.6) and blood urea
      nitrogen (BUN) levels >/= 20 mg/dL (odds ratio, 3.0; 95% CI, 1.1-8.3) were
      correlated significantly with mortality. CONCLUSIONS: Pneumonia was the major
      pulmonary complication in hospitalized patients with CLL. Severe neutropenia and
      high BUN levels were correlated significantly with increased mortality.

PMID- 14584075
TI  - A phase II study of weekly docetaxel plus capecitabine for patients with advanced
      nonsmall cell lung carcinoma.
AB  - BACKGROUND: Docetaxel is an active agent in advanced nonsmall-cell lung carcinoma
      (NSCLC) and demonstrates preclinical and clinical synergism with capecitabine. We
      conducted the current Phase II study to evaluate the efficacy and safety of the
      docetaxel/capecitabine combination in chemotherapy-naive patients with advanced
      NSCLC. METHODS: Eligibility required Stage IIIB or IV NSCLC, bidimensionally
      measurable disease, and an Eastern Cooperative Oncology Group performance score
      of 2 or lower. Treatment consisted of docetaxel 36 mg/m(2) intravenously on Days
      1 and 8 plus capecitabine 1000 mg/m(2) orally twice per day on Days 1-14 of a 21
      day cycle, for a maximum of 6 cycles. RESULTS: Of 39 patients enrolled, 39 and 36
      patients were evaluated for toxicity and response, respectively. The overall
      response rate was 53% (95% confidence interval [CI], 37-69%) with 19 partial
      responses (no complete response). The median duration of response was 6.2 months
      (range, 2.1-15.7 months). At a median follow-up of 14.2 months, 19 patients died.
      The median overall survival time was 17.8 months, with a 1-year survival rate of
      56.4% (95% CI, 40.9-72.0%). There were two treatment-related deaths (one death
      due to pneumonia and one due to sepsis). Hematologic toxicity was mild to
      moderate. Thirteen percent of the patients had Grade 3 or 4 neutropenia. However,
      Grade 2 or 3 nonhematologic toxicities were frequent, which included asthenia
      (51%), stomatitis (33%), hand-foot syndrome (33%), and diarrhea (29%).
      CONCLUSIONS: The docetaxel/capecitabine combination showed promising antitumor
      activity for chemotherapy-naive patients with advanced NSCLC, However, it was
      frequently associated with moderate-to-severe nonhematologic toxicities,
      suggesting clinical synergism in both efficacy and toxicity. Further adjustment
      of the dose schedule is recommended to maximize the therapeutic index.

PMID- 14584076
TI  - Metastasis of esophageal carcinoma to the brain.
AB  - BACKGROUND: Esophageal carcinoma rarely metastasizes to the brain. The objectives
      of the current study were to assess the frequency of brain metastasis from an
      esophageal primary tumor, to determine correlates of survival, and to describe
      treatment modalities and their outcomes. METHODS: Between June, 1993 and July,
      2001, 1588 patients with a primary esophageal carcinoma registered at The
      University of Texas M. D. Anderson Cancer Center; of those, 27 patients (1.7%)
      had a diagnosis of brain metastasis. The authors collected demographic and
      clinical data and performed a statistical analysis. RESULTS: The median age at
      the time patients were diagnosed with brain metastasis was 62 years. Tumor
      histologies were adenocarcinoma in 22 patients (82%), unclassified carcinoma in 3
      patients (11%), and squamous cell carcinoma in 2 patients (7%). Twenty patients
      (74%) experienced symptoms related to the brain metastasis. The metastases were
      treated with whole-brain radiation therapy (WBRT) alone in 15 patients (56%), and
      10 patients (37%) underwent surgical resection, 4 of whom (15%) also received
      WBRT. Two patients (7%) underwent stereotactic radiosurgery. The median survival
      for the entire cohort after diagnosis of the primary tumor was 12.6 months (95%
      confidence interval [CI], 2.17-22.5 months), and the median survival after the
      diagnosis of brain metastasis was 3.8 months (95% CI, 1.1-6.5 months). The
      longest median survival observed after the diagnosis of brain metastasis (9.6
      months) occurred in patients with a single brain lesion who underwent resection
      and received WBRT. There was a trend toward worse survival in patients with liver
      metastases and patients in recursive partitioning analysis (RPA) Class II-III
      versus RPA Class I (P = 0.10 for both; multivariate Cox proportional hazards
      model analysis). CONCLUSIONS: Approximately 2% of patients with esophageal
      carcinoma had a diagnosis of brain metastasis. Improved outcome was associated
      with single brain lesions in patients who underwent surgery and received WBRT.
      Known liver metastasis and higher RPA scores were associated with a poorer
      survival trend.

PMID- 14584077
TI  - Skull base and nonskull base chordomas: clinicopathologic and immunohistochemical
      study with special reference to nuclear pleomorphism and proliferative ability.
AB  - BACKGROUND: To the authors' knowledge, little is known regarding the relation
      between the proliferative ability and clinicopathologic parameters in skull base
      chordomas (SBCs) and nonskull base chordomas (NSBCs). METHODS: The authors
      investigated 122 conventional chordomas for their clinicopathologic parameters,
      proliferative ability (MIB-1 labeling index [LI]) and clinical outcome. RESULTS:
      Primary NSBCs were found to affect more elderly patients and demonstrated a
      higher MIB-1 LI compared with primary SBCs. Mitosis was more commonly noted in
      recurrent NSBCs compared with primary NSBCs. Apoptosis was more frequent in
      elderly patients than in younger patients with regard to both SBCs and NSBCs.
      Apoptosis also was found to be correlated with necrosis in SBCs, suggesting a
      common factor for the two different types of cell death. Mucoid matrix was
      reported to be more abundant in NSBCs than in SBCs, and appeared to occur more
      often in elder NSBC patients compared with younger NSBC patients. This indicates
      that it is produced in the later stages of tumorigenesis. In SBCs, several
      clinicopathologic parameters were found to be correlated with MIB-1 LI. Among
      them, increased age, recurrence, and nuclear pleomorphism were the only
      independent factors found to indicate a higher MIB-1 LI. No such parameters were
      found in NSBCs. However, in these lesions, prognosis was significantly poorer in
      those cases with nuclear pleomorphism compared with those without. CONCLUSIONS:
      The results of the current study suggest that nuclear pleomorphism is a
      prognostic indicator in NSBCs. The proliferative ability of SBCs appears to be
      closely associated with patient age, clinical status (recurrence), and nuclear
      pleomorphism.

PMID- 14584078
TI  - A phase II trial of temozolomide in patients with unresectable or metastatic soft
      tissue sarcoma.
AB  - BACKGROUND: The objective of this study was to assess the efficacy and toxicity
      of the imidazotetrazine derivative temozolomide for patients with unresectable or
      metastatic soft tissue sarcoma. METHODS: Twenty-five of 26 patients were eligible
      and assessable for toxicity and response. Temozolomide was administered twice
      daily on a 12-hour schedule for 5 days as an oral bolus dose of 200 mg/m(2)
      followed by 9 doses of 90 mg/m(2) every 4 weeks. RESULTS: There were 2 partial
      responses, 2 mixed responses, and 3 patients with stable disease that lasted > 6
      months, for an overall objective response rate of 8%. At a median follow-up of
      13.2 months, the median progression-free survival and the median overall survival
      were 2.0 months (95% confidence interval [95% CI], 1.7-2.3) and 13.2 months (95%
      CI, 4.7-31.1), respectively. All responding patients had leiomyosarcoma of
      uterine or nonuterine origin; and, in a subset analysis of these patients, the
      objective response rate was 18% (2 of 11 patients), with disease stabilization
      occurring in 3 of 11 patients (27%). For this subgroup, at a median follow-up of
      24.4 months, the median progression-free survival and the median overall survival
      were 3.9 months (95% CI, 1.9-21.9) and 30.8 months (lower-bound 95% CI, 7.8),
      respectively. There were no treatment-related deaths or National Cancer Institute
      Grade 4 toxicities. Grade 3 toxicities included nausea, anemia, fatigue, elevated
      alkaline phosphatase levels and nonneutropenic fever (1 patient each).
      CONCLUSIONS: Temozolomide at the dose schedule employed in the current study was
      tolerated well and had modest activity against previously treated unresectable or
      metastatic leiomyosarcoma of both uterine and nonuterine origin.

PMID- 14584079
TI  - Familial sarcoma: challenging pedigrees.
AB  - BACKGROUND: Partially due to the rare occurrence of soft tissue and osteogenic
      sarcomas in the general population, scant attention has been given to their
      hereditary etiology. Their overall poor prognosis might be ameliorated through an
      understanding of their environmental and hereditary causal factors, and/or their
      interactions, thereby contributing to earlier diagnosis and even the development
      of molecularly based targeted therapy. METHODS: The authors selected 10 sarcoma
      prone families from their extensive hereditary cancer-prone family resource and
      focused on their challenging diagnostic, surveillance, and management features.
      The family study protocol included the compilation of a detailed family history
      of malignant disease of all anatomic sites and the collection of all available
      primary medical and pathology documents for verification. Genetic counseling was
      provided before DNA collection and at disclosure of results. RESULTS: These
      families displayed marked phenotypic and genotypic heterogeneity. In one of these
      families, 16 relatives had sarcomas, with 2 of the 16 each having 2 metachronous
      sarcomas; to our knowledge, this represents the greatest number of sarcomas
      reported in any family described to date. Two familial atypical multiple-mole
      melanoma syndrome kindreds with the CDKN2A mutation showed the association of
      sarcoma with malignant melanoma, whereas one family had several pancreatic
      carcinomas. Other families with sarcoma had hereditary nonpolyposis colorectal
      carcinoma with MSH2 mutation, hereditary breast carcinoma with BRCA1 mutation,
      and p53 mutation in a Li-Fraumeni syndrome. CONCLUSIONS: Sarcoma-prone families
      reported in the current study were selected carefully to depict clinicopathology
      and compliance features, the understanding of which could elucidate the etiologic
      role of genetic factors in concert with the phenotypic and genotypic
      heterogeneity encountered in such families. The lack of a population-based data
      set for these families posed a limitation.

PMID- 14584080
TI  - Reduced folate carrier protein expression in osteosarcoma: implications for the
      prediction of tumor chemosensitivity.
AB  - BACKGROUND: High-dose methotrexate (MTX) is an important component of current
      protocols for the treatment of osteosarcoma. Although MTX uptake proceeds
      primarily through the reduced folate carrier (RFC) protein and efflux occurs via
      multidrug resistance protein 1 (MRP1), RFC protein expression in osteosarcoma
      remains unexamined. METHODS: RFC and MRP1 expression (normalized to beta-actin
      expression) was examined with Western blot analysis in 11 osteosarcoma specimens
      obtained at diagnosis and 9 osteosarcoma specimens obtained on recurrence.
      RESULTS: The average RFC level in specimens obtained on recurrence was
      significantly higher than the level in specimens obtained at diagnosis (P =
      0.0005). Furthermore, in all three matched pairs of diagnosis and recurrence
      specimens, RFC levels were higher in recurrence specimens than in the
      corresponding diagnosis specimens. Potential correlations between RFC and MRP1
      expression and histologic response to preoperative chemotherapy were examined.
      Tumors with poor histologic responses (i.e., </= 90% necrosis) had significantly
      lower RFC levels than did those with favorable responses to chemotherapy (P =
      0.0016). In contrast, there was no correlation between MRP1 levels at diagnosis
      and histologic response to chemotherapy (P = 0.8764). The elevated MRP1 levels in
      specimens obtained on recurrence relative to MRP1 levels in specimens obtained at
      diagnosis were not statistically significant (P = 0.2056). CONCLUSIONS: The
      significant correlation between low RFC levels at diagnosis and poor histologic
      response to preoperative chemotherapy suggests that RFC levels at diagnosis may
      be a useful predictor of chemosensitivity and warrants large-scale studies. In
      addition, postchemotherapy progression to recurrence is associated with a
      significant increase in RFC expression. To our knowledge, the current study is
      the first to examine RFC protein levels in tumor specimens. Cancer 2003.

PMID- 14584082
TI  - Estimation of an optimal radiotherapy utilization rate for breast carcinoma: a
      review of the evidence.
AB  - BACKGROUND: Radiotherapy utilization rates for breast carcinoma vary widely, both
      within and between countries. Current estimates of the proportion of patients
      with carcinoma who optimally should receive radiotherapy are based either on
      expert opinion or on the measurement of actual utilization rates, and not on the
      best scientific evidence. METHODS: To develop an evidence-based benchmark for
      radiotherapy utilization in patients with breast carcinoma, the authors undertook
      a systematic review of treatment guidelines on the use of radiotherapy for breast
      carcinoma. A decision tree was constructed, and the proportions of patients with
      clinical features that lead to a decision for radiotherapy were obtained from
      epidemiological data. This ideal utilization rate was compared with the
      utilization rates of radiotherapy over the last decade for breast carcinoma in
      Australia and internationally. RESULTS: The proportion of patients with breast
      carcinoma in whom radiotherapy would be recommended according to the best
      available evidence was calculated at 83% (95% confidence interval, 82-85%) of all
      patients with breast carcinoma. A review of actual radiotherapy utilization rates
      for breast carcinoma revealed that, in clinical practice, actual utilization
      rates varied between 24% and 71%. CONCLUSIONS: A substantial difference was found
      between the recommended optimal utilization of radiotherapy based on evidence and
      the actual rates reported in clinical practice. The reasons for these differences
      need to be examined, and a plan for addressing the suboptimal use of radiotherapy
      needs to be implemented. Cancer 2003.

PMID- 14584081
TI  - The analysis of immunophenotype of gastrin-producing tumors of the pancreas and
      gastrointestinal tract.
AB  - BACKGROUND: Gastrinomas are located more frequently in the pancreas, which
      normally has no cells that can produce gastrin. They have a more aggressive
      course than other pancreatic endocrine tumors and extrapancreatic gastrinomas
      associated with multiple endocrine neoplasia Type 1 syndrome. The current study
      analyzed immunophenotypes of gastrinomas and compared them with other pancreatic
      endocrine tumors. METHODS: Twenty-one formalin-fixed, paraffin-embedded specimens
      (15-tumors in the pancreas, 1 in the duodenum, 1 in the stomach, 1 in the liver,
      and 3 of unknown primary location) accompanied by Zollinger-Ellison syndrome and
      17 other pancreatic endocrine tumor specimens were investigated. They were
      stained immunohistochemically for gastrin, chromogranin A, synaptophysin,
      insulin, glucagon, somatostatin, pancreatic polypeptide, calcitonin, serotonin,
      chorionic gonadotropin, adrenocorticotropic hormone, carcinoembryonic antigen,
      epithelial membrane antigen, and cytokeratin 19. RESULTS: Gastrinomas coexpressed
      neuroendocrine and exocrine markers, including chromogranin A, synaptophysin,
      carcinoembryonic antigen, cytokeratin 19, and epithelial membrane antigen.
      Carcinoembryonic antigen was found in all 17 gastrinomas (100%), cytokeratin 19
      was found in 15 of 17 (88.2%) gastrinomas, and epithelial membrane antigen was
      found in 16 of 18 (88.9 %) gastrinomas. Cytokeratin 19, epithelial membrane
      antigen, and carcinoembryonic antigen were not found to be present in the
      pancreatic endocrine tumors, but chromogranin A and synaptophysin were. Chorionic
      gonadotropin was found in 16 gastrinomas (100%), but only in 2 of 17 other
      pancreatic endocrine tumors (11.8 %). CONCLUSIONS: Pancreatic gastrinomas were
      characterized by the coexpression of neuroendocrine markers, exocrine markers,
      and chorionic gonadotropin. Therefore, pancreatic gastrinomas made a special
      intermediate group of tumors, which phenotypically combined features of
      neuroendocrine and exocrine neoplasms. These findings suggested that sporadic
      pancreatic gastrinomas and other pancreatic endocrine tumors are different
      phenotypically and are possibly of different origin.

PMID- 14584083
TI  - The 1999 patterns of care study of radiotherapy in localized prostate carcinoma:
      a comprehensive survey of prostate brachytherapy in the United States.
AB  - BACKGROUND: The objective of the current study was to provide descriptive
      information on a representative national sample of patients with prostate
      carcinoma who were treated with prostate brachytherapy (PB) in calendar year
      1999. METHODS: A random survey was conducted by the Patterns of Care Study in
      radiation oncology of 59 facilities (1 facility had no eligible patients) that
      treated patients with prostate carcinoma in 1999 in the United States. A weighted
      sample size of 36,496 patients with prostate cancer was included in the 1999
      survey (unweighted sample size, 554 patients). The main measures were the
      clinical characteristics of men prior to treatment and the technical
      characteristics of PB. Patients were classified into three prognostic groups
      according to T stage, pretreatment prostate specific antigen (PSA) level, and
      Gleason score. RESULTS: A weighted sample size of 13,293 patients (36%;
      unweighted sample size, 162 patients) was treated with PB. Compared with a
      weighted sample size of 23,203 patients (64%; unweighted sample size, 392
      patients) was treated with external beam radiotherapy (EB), patients who received
      PB were significantly younger (mean age: PB group, 67.7 years; EB group, 70.8
      years; P = 0.0006). The mean pretreatment PSA level for the PB group was lower
      compared with the EB group (9.9 ng/mL vs. 13.33 ng/mL; P = 0.0015). The
      prognostic groupings were more favorable for patients in the PB group compared
      with patients in EB group (P = 0.0365). The utilization of androgen deprivation
      therapy (ADT) in the PB group was similar to the utilization of ADT in the EB
      group (40.4% vs. 51.3%; P = 0.2282). The vast majority of men who were treated
      with PB received low-dose-rate, permanent sources (89%). Fifty-four percent of
      men received PB monotherapy (PBM), and the remaining 46% were treated with EB in
      addition to PB (EBPB). The prognostic groupings were more favorable for patients
      in the PBM group compared with patients in the EBPB group (P = 0.0037). Of the
      men who were treated with low-dose-rate PB, 59% were treated with iodine-125 (I
      125), and 41% were treated with palladium-103 (Pd-103). I-125 was used more
      frequently in men who were treated with PBM, and Pd-103 was used more frequently
      in men who were treated with EBPB. Postimplantation dosimetry was documented in
      61.0% of men who were treated with low-dose-rate PB. Computed tomography imaging
      was used for 46.5% of men. CONCLUSIONS: PB was used in 36% of men who were
      treated with radiotherapy nationally. The mean age of men who were treated with
      PB was younger than the population of men who were treated with EB alone. Nearly
      50% of men who received PB also received EB. EB was used more frequently in men
      with higher-risk disease. ADT was used in 40% of patients in the PB group.
      Techniques and prescription doses were consistent with published guidelines.

PMID- 14584084
TI  - Urinary levels of urokinase-type plasminogen activator and its receptor in the
      detection of bladder carcinoma.

PMID- 14584085
TI  - Pure versus follicular variant of papillary thyroid carcinoma: clinical features,
      prognostic factors, treatment, and survival.

PMID- 14584087
TI  - Echinococcus against cancer: why not?

PMID- 14584089
TI  - Combined treatment with vitamin k2 and bisphosphonate in postmenopausal women
      with osteoporosis.
AB  - Vitamin K2, as well as bisphosphonates, such as etidronate, alendronate, and
      risedronate, is widely used in the treatment with osteoporosis in Japan.
      Etidronate increases the lumbar bone mineral density (BMD), and prevents new
      vertebral fractures, in patients with osteoporosis, while alendronate and
      risedronate increase the lumbar and femoral neck BMDs, and prevent new vertebral
      and femoral neck fractures. Vitamin K2 enhances gamma-carboxylation of bone
      glutamic acid residues and the secretion of osteocalcin, sustains the lumbar BMD,
      and prevents osteoporotic fractures in patients with osteoporosis.
      Bisphosphonates, such as alendronate and risedronate, rather than vitamin K2,
      should be initially chosen for the treatment of osteoporosis, because they are
      more efficacious than vitamin K2. Available evidence suggest that risedronate
      prevents deterioration of the connectivity of the trabeculae in ovariectomized
      rats, whereas vitamin K2 increase the trabecular thickness, and that a
      combination of risedronate and vitamin K2 has a synergistic effect on preventing
      the deterioration of trabecular bone architecture induced by estrogen deficiency.
      Some studies have shown that combined treatment with etidronate and vitamin K2
      appears to be more effective than etidronate alone in the prevention of new
      osteoporotic vertebral fractures. Based on these findings, combined treatment
      with vitamin K2 and bisphosphonates may be more efficacious in the prevention new
      vertebral fractures than a single treatment with bisphosphonate in postmenopausal
      women with osteoporosis. Thus, this combined treatment should be recommended for
      the treatment of postmenopausal osteoporosis. It is proposed that the role of
      vitamin K2 should be emphasized, when used in combination with bisphosphonates,
      especially in patients with vitamin K deficiency.

PMID- 14584090
TI  - Eleven-year experience of low grade lymphoma in Korea (based on REAL
      classification).
AB  - Low grade lymphomas are malignancies of predominantly small lymphocytes that
      typically have long median survival periods due to low proliferative rates. It is
      considered an indolent disease, but patients with low grade lymphoma can almost
      never be cured with conventional treatment. New low- grade lymphoma entities have
      been classified by the International Lymphoma Study Group (ILSG) and are also
      categorized into the Revised European American Lymphoma (REAL) classification.
      The REAL classification utilizes a multiparameter definition of clinico
      pathologic and biologic entities. According to this classification, we
      investigated the incidence, various clinical characteristics, treatment outcome
      and prognostic factors of low grade lymphoma. Many clinical characteristics of
      low grade lymphoma in Korea differed from those of Western countries, especially
      in the incidence, therapeutic outcome and prognostic factors. In Korea, although
      the general incidence of low grade lymphoma is relatively low, the relative
      number of mucosa-associated lymphoid tissue lymphoma (MALToma) is very high, and
      the overall survival rate is better than that reported of Western countries.
      Thus, further investigation on treatment outcome and prognosis of low grade
      lymphoma entities, other than mucosa- associated lymphoid tissue lymphoma, are
      warranted.

PMID- 14584091
TI  - The serum vitamin C levels in Behcet's disease.
AB  - Behcet's disease (BD) is a chronic inflammatory disorder of unknown aetiology,
      and recognised as a multi-system vasculitis. It has been postulated that an
      imbalance of the oxidant and antioxidant systems related to the disease are
      important in its pathogenesis. Previous publications have reported increased
      levels of enzymatic antioxidant defence systems in patients with BD. The non
      enzymatic antioxidant systems, including vitamin C and uric acid, were looked for
      in the present study. For this aim, the serum malondialdehyde (MDA), an end
      product of lipid peroxidation, and vitamin C and uric acid, as endogenous
      antioxidants, were determined in 20 patients with BD (11 in active and 9 in
      inactive periods) and 20 healthy subjects. The MDA level was significantly higher
      in both the active and inactive period patients compared with the control group
      (p < 0.001, p < 0.05, respectively). The MDA level was also significantly higher
      in the active period patients compared with the inactive period patients (p <
      0.05). The vitamin C levels were significantly lower in both the active and
      inactive period patients compared with the control group (p < 0.001, p < 0.05,
      respectively). There was no significant difference in the vitamin C level between
      the active and inactive period patients (p > 0.05). There was also no significant
      difference in uric acid levels between the groups (p > 0.05). In the patients
      group, a negative correlation was found between the levels of serum MDA and
      vitamin C (r=-0.517; p < 0.05). Our results indicate that decreased vitamin C and
      increased MDA levels reflect the increased levels of oxidative stress in BD
      patients, and this situation may be important in relation with its pathogenesis.

PMID- 14584092
TI  - 18F-fluorodeoxyglucose-positron emission tomography in the staging of malignant
      lymphoma compared with CT and 67Ga scan.
AB  - The accurate staging of Hodgkin's disease (HD) and non- Hodgkin's lymphoma (NHL)
      is an important aspect of treatment. In this study, the authors undertook to
      prospectively evaluate the clinical value of 2-(fluorine-18)fluoro-2-deoxy-D-
      glucose position emission tomography (FDG-PET) for the staging of malignant
      lymphoma as compared with computed tomography and 67Ga scan. Thirty consecutive
      cases with biopsy-proven lymphoma (4 HD, 26 NHL) were examined by FDG-PET for the
      initial staging and the restaging work-up between September 2000 and April 2001.
      The FDG-PET and conventional study, including a CT of the neck, chest, abdomen,
      and of the pelvis, a bone scan, a 67Ga scan, and a bone marrow study were
      undertaken to investigate nodal/extranodal manifestations and bone marrow
      infiltration. In terms of the detection of nodal lymphoma manifestation, the
      sensitivities and specificities of the PET, CT, and 67Ga scan were determined to
      be 93.3%, 98.9%, and 25.8%, and 100%, 99.1%, and 99.8%, respectively. In terms of
      the detection of extranodal lymphoma manifestation, the sensitivities and
      specificities of the PET, CT, and 67Ga scan were 87.5%, 87.5%, and 37.5%, and
      100%, 100%, and 100%, respectively. The FDG-PET proved to be very accurate for
      the staging of malignant lymphoma and superior to Ga-67 scan. Although the
      results of PET and CT were substantially comparable, both imaging studies were
      found to complement each other in some cases with respect to the evaluation of
      lymphomatous involvement.

PMID- 14584093
TI  - Dopamine transporter genotype influences the attention deficit in Korean boys
      with ADHD.
AB  - Attention appears to be inheritable, stable and influenced by genetic factors.
      The use of the Continuous Performance Test (CPT), as an endophenotypic measure,
      is valuable for genetic studies because it may show increased sensitivity to
      specific dimensions in attention deficit hyperactivity disorder. However, few
      studies have been designed to examine the influence of the genotype on attention
      level measured by CPT in ADHD patients. This study examinee the difference
      between 10/10 and 10/* genotype in the attention deficits measured by the CPT in
      ADHD patients. Forty-four unrelated ADHD patients were recruited from the
      psychiatric outpatients' clinic at Kangbuk Samsung Hospital. Two child
      psychiatrists made the diagnoses of ADHD using the DSM- IV diagnostic criteria.
      The genomic DNA was extracted from the blood, and analyzed to determine the
      genotype. A 40- base pair variable number of tandem repeats (VNTR) polymorphism
      in the 3' untranslated region was amplified. The attention deficits were measured
      by the test of variables of attention (T.O.V.A.). Between the 10/10 genotype and
      10/* genotype, standard scores of the T.O.V.A were compared using a Mann-Whiney
      test. A comparison with the 10/10 genotype and 10/* genotype showed that those
      patients with the 10/10 genotype made less omission errors in the first quarter
      of the test (p < 0.05, by Mann-Whiney test). No significant differences were
      observed in the errors of commission, response time, variability. This study
      found that the 10/10 genotype made less omission errors on the T.O.V.A. This
      suggests that the dopamine transporter genotype influences the attention deficits
      measured by T.O.V.A.

PMID- 14584094
TI  - Anger and coronary calcification in individuals with and without risk factors of
      coronary artery disease.
AB  - The authors investigated the relationship between anger and the calcification of
      the coronary artery in individuals with and without risk factors for coronary
      artery disease in Korea. Sixty-one subjects with risk factors of coronary artery
      disease and 31 subjects without risk factors were enrolled in this study.
      Electron Beam Computed Tomography was used to measure the calcium level of
      coronary artery. The anger expression scale was used to measure the anger levels.
      The anxiety, depression, hostility, and somatization subscales of the symptom
      checklist-90-revised (SCL-90-R) and the global assessment of recent stress (GARS)
      scale were used to assess the psychopathology and perceived stress. The logistic
      regression analysis results showed that only the anger-total score was
      significantly associated with the coronary calcification regardless of the risk
      factors. These results suggest that anger plays an important role in the
      calcification of the coronary artery.

PMID- 14584095
TI  - The efficacy of high-dose melphalan with autologous peripheral blood stem cell
      transplantation in patients with multiple myeloma.
AB  - Although high-dose therapy (HDT) with autologous hematopoietic stem cell
      transplantation (ASCT) is widely accepted as an effective and safe consolidation
      therapy for multiple myeloma (MM), few reports on its efficacy are available in
      Korea. We present the results of a prospective phase II study, involving 33
      patients with MM treated with HDT with ASCT. The treatment consisted of 4 courses
      of VAD (vincristine, adriamycin, dexamethasone) induction, peripheral blood stem
      cell collection, and high-dose melphalan with stem cell infusion. The overall
      response rate was 93%, with 45% of patients having complete responses. The
      toxicity was predictable and tolerable. With a median follow-up of 27.6 months,
      the 2-year event free survival rate was 43%. At the time of writing, the median
      overall survival duration had not been reached with 2-year survival and projected
      3-year survival rates of 81% and 74%, respectively. The overall survival was
      significantly better than that of the historical control patients (N=82) treated
      with conventional chemotherapy at our institution. The results suggest that HDT
      with ASCT is a valuable first or second-line treatment for patients with MM.

PMID- 14584096
TI  - Correlations between microcomputed tomography and bone histomorphometry in Korean
      young females.
AB  - The bone mass and microarchitecture are important determinants of bone strength,
      with microarchitectural deterioration being one of the specific changes
      associated with osteoporosis. The purpose of this study was to evaluate and
      compare the results of microcomputed tomography (micro-CT) and histomorphometry
      of biopsied specimens. A bone biopsy was performed on the iliac crest of 10
      normal premenopausal Korean women. Measurements of the bone mineral density
      (BMD), micro-CT, and bone histomorphometry were performed. The bone volume, as
      determined by both micro-CT and histomorphometry, was significantly correlated
      (r=0.88, p < 0.01). The osteoid surface was correlated with both the bone volume
      (r=0.84, p < 0.01) and the structure model index (SMI) (r= -0.89, p < 0.01)
      measured by micro-CT. The SMI was correlated with both the bone volume (r=-0.85,
      p < 0.01) and the total hip BMD (r=-0.65, p < 0.05). In conclusion, some, but not
      all of the parameters of the micro-CT, were well correlated with the bone
      histomorphometric results. Micro-CT and histomorphometry appear to be
      complementary techniques in the study of bone microarchitecture.

PMID- 14584097
TI  - Intranuclear cytoplasmic pseudoinclusions in pituitary adenomas.
AB  - Intranuclear pseudoinclusions are well known in papillary carcinomas of the
      thyroid gland, hepatocellular carcinomas, meningiomas, paragangliomas,
      pheochromocytomas, and melanomas. Only two papers on the intranuclear inclusions
      of adenohypophyseal cells in humans have been reported. This study found that
      intranuclear cytoplasmic pseudoinclusions occur frequently in pituitary adenoma
      cases (70.3%, 97 of 138 pituitary adenomas) and are uncommon in normal pituitary
      tissue (11.1%, 1 of 9 normal pituitary tissues). In addition, the frequency of
      intranuclear cytoplasmic pseudoinclusions between the functional and non
      functional pituitary adenomas was found to be similar. Electron microscopy and
      immunostaining was used to reveal the entity of the intranuclear inclusion. These
      intranuclear inclusions are due to cytoplasmic invagination because 1) the
      inclusions are continuous with the cytoplasm, 2) all cytoplasmic organelles, such
      as the endoplasmic reticulum, the Golgi apparatus, and the secretory granules are
      found in the inclusions, 3) immunoreactivity of the intranuclear inclusion is the
      same as that of the cytoplasm. In conclusion, intranuclear cytoplasmic
      pseudoinclusions in pituitary adenomas occur frequently (70.3%) and are formed by
      cytoplasmic invagination. This study suggests that pituitary intranuclear
      inclusions caused by cytoplasmic invagination be called "intranuclear cytoplasmic
      pseudoinclusions".

PMID- 14584098
TI  - Choroidal neovascularization characteristics and its size in optical coherence
      tomography.
AB  - The classification, size and activity of choroidal neovascularization (CNV) by
      optical coherence tomography (OCT) were compared with those obtained by
      fluorescein angiography (FA) and Indocyanine green angiography (ICG). This study
      included 32 patients (32 eyes) diagnosed as having CNV. The etiology of CNV was
      found to be age-related macular degeneration (AMD) or non-AMD. Patients were
      studied retrospectively by FA, ICG, and OCT. Of the 13 eyes with AMD, the
      boundary of the lesion could not be defined using FA in 7 patients. Among the 7
      poorly defined CNV cases by FA, the identification of the boundary was possible
      in one case by OCT. The mean diameter of the classic well-defined lesions was
      3500 +/- 421 microm by FA, 2624 +/- 1044 microm by ICG, and 1927 +/- 1272 microm
      by OCT. The size of the CNV by OCT was always smaller than by FA or ICG. Of the
      19 eyes with Non-AMD, the boundary of the lesion could not be defined by FA in 5
      patients. Among the 5 poorly defined cases by FA, the identification of the
      boundary was possible in 3 cases by OCT. The mean diameter of the well-defined
      CNV lesions was 2153 +/- 759 microm by FA, 1929 +/- 673 microm by ICG, and 1322
      +/- 566 microm by OCT. Retinal thickness, which represents retinal edema, was
      found to be proportional to lesion size, although the relationship was not
      statistically significant. Regardless of CNV type, FA, ICG and OCT used in
      combination increase the specificity of diagnosis if their findings are compared.

PMID- 14584099
TI  - The effect of supraclavicular lymph node irradiation upon the thyroid gland in
      the post-operative breast carcinoma patients.
AB  - To identify the effect of post-operative irradiation to the thyroid gland in
      patients with breast carcinoma. Seventy seven patients with partial or total
      mastectomized breast carcinoma who received routine irradiation therapy (Hockey
      stick method: supraclavicular, internal mammary lymph nodes, and chest wall
      irradiation with 5,040 rads, divided into 30 treatments) were reviewed in terms
      of their ipsilateral thyroid gland response. All patients had the bilateral
      thyroid sizes measured annually by ultrasonography before and after radiation
      therapy. In the one-year follow-up group (n=77), 32 patients (41.5%) demonstrated
      decreased ipsilateral thyroid gland size after Hockey Stick irradiation therapy
      (p=0.428), in the two-year follow-up group (n=37), 26 patients (70.3%)
      demonstrated decreased gland size after Hockey Stick irradiation (p=0.001), and
      in the three-year follow-up group (n=21), 15 patients (71.4%) showed a decreased
      thyroid gland size (p=0.005). Most the patients with breast carcinoma (32/77 at
      the one-year follow-up, 26/37 at the two-year follow-up, and 15/21 at the three
      year follow-up) after post-operative Hockey Stick irradiation therapy showed
      reduced ipsilateral thyroid gland size. Routine en face treatment of the
      supraclavicular lymph nodes, using the Hockey Stick method, should be
      reconsidered.

PMID- 14584100
TI  - Conservative treatment in intra-articular fractures of the distal radius: a study
      on the functional and anatomic outcome in elderly patients.
AB  - Fractures of the distal radius are common among elderly patients. Although the
      indications for surgical treatment are clearly defined, there are patients who
      will not consent to an operation, even when it is indicated. Inevitably, these
      cases will require conservative treatment. The aim of this study was to determine
      the relation between the functional and anatomic stati of these patients. One
      hundred and eight patients, with intra-articular distal radial fractures, who had
      been treated non-surgically, were investigated in this study. Functional and
      anatomic assessments were also performed. The mean follow up period was 39.5
      months. The mean age of the subjects was 73.9 years. Although 25.9% of the
      patients had fair and poor anatomic scores, 88.9% were considered to have good
      and excellent functional results.

PMID- 14584101
TI  - Comparative Ki-67 expression and apoptosis in the odontogenic keratocyst
      associated with or without an impacted tooth in addition to unilocular and
      multilocular varieties.
AB  - It is not known whether the presence of an impacted tooth or the radiographic
      types in an odontogenic keratocyst (OKC) change the clinical biologic behavior
      and therapeutic approaches. This study evaluated the comparative proliferative
      activity and apoptosis in OKC associated with or without an impacted tooth, as
      well as between the unilocular and multilocular OKC varieties.
      Immunohistochemical expression of Ki-67 as a proliferation marker and the
      apoptotic reactions were assessed by the TUNEL method for 32 cases of OKC (OKC
      with impacted tooth, n=16; OKC without impacted tooth, n=16) and 10 cases of
      dentigerous cyst (DC). OKC showed a greater proliferative potential and more
      apoptotic reactions than DC. In particular, OKC contained proliferating and
      apoptotic cells situated predominantly in the suprabasal and superficial layers,
      respectively. However, no significant difference was found between OKC associated
      with or without impacted tooth, or between the unilocular and multilocular OKC
      varieties, in terms of proliferative activity or apoptosis. In conclusion, OKC is
      characterized by an increase in both cell proliferation and apoptosis, suggesting
      a unique proliferative and differentiation process. It is believed that
      incomplete removal or other contributing factors, rather than intrinsic growth or
      apoptosis, may be the main reasons for the aggressive biologic behavior or
      recurrence in multilocular OKC.

PMID- 14584102
TI  - Sonographic findings of breast hamartoma: emphasis on compressibility.
AB  - The characteristic features of hamartoma in terms of discrepancies in
      mammographic and sonographic shapes of the mass were evaluated. We reviewed 16
      pathologically proven breast hamartomas, which had undergone preoperative
      mammography and ultrasonography. All masses were analyzed according to ACR-BIRADS
      on mammography. On sonography, each mass was analyzed for size, shape, margin,
      internal echogenicity, and posterior acoustic enhancement. We also analyzed the
      echogenicity of halo, and compared the characteristic changes in the shape of
      hamartomas attributable to compression in mammograms and sonograms. The most
      common sites were at 12 o'clock in the right breast and 2 o'clock in the left.
      The most common mammographic findings of the hamartomas were a round shape
      (11/16), a circumscribed margin (13/16), internal fat densities (D4)(16/16) and
      radiolucent halos (14/16). The most common sonographic findings of the hamartomas
      were an oval shape (16/16), circumscribed margins (10/16), heterogeneous internal
      echogenicity (14/16), echogenic (7/16) or echolucent halos (5/16), and posterior
      enhancements (12/16). The characteristic feature of hamartomas was a change of
      the mammographic round shape mass into an elongated oval shape mass by sonography
      (11/11), suggesting the compressibility of hamartomas. Three of the hamartomas
      contained a pathologically proven internal calcification. The presence of a
      hamartoma was suggested by a change in a mammographic round mass with a
      radiolucent halo into an oval heterogeneous mass surrounded by an echogenic or
      echolucent halo on the sonogram. This characteristic difference between the
      mammographic and sonographic findings was attributed to the hamartoma
      compressibility, and was associated with the over-proliferation of fat containing
      mature normal breast tissue.

PMID- 14584103
TI  - Morphological study on the acetabular labrum.
AB  - For the diagnosis and treatment of the labral pathology, the cross sectional
      morphology of the labrum is needed. Fifty-four labra (male:female=44:10) from 32
      adult Korean cadavers were cut in radial and perpendicular fashions to their
      longitudinal axis. Each labrum was divided into 8 segments, resulting 8 equally
      distanced points. To analyze the 432 cut surfaces, which consisted of 378 labra
      and 54 transverse acetabular ligaments cut surfaces, all dimensions of the cut
      surfaces were measured, and the attachment patterns, including the sublabral
      slit, observed. The shapes of the cut surfaces were classified into four types (3
      subtypes of triangle and 1 quadrangle) and the attachment patterns into five
      types. At the anterior portion of the labrum, which other studies reported as the
      predilection area for labral tears, there were several common findings: 1) Tall
      triangular shapes were dominant (61.1%) or relatively common type (25.9%). 2) The
      average heights of the labrum were longer (7.4 and 7.0 mm) than at the other
      sites (4.0 - 6.8 mm). 3) The attachment types with no extra-extended portion
      (68.5%) and sublabral slits (39.0%) were most commonly observed. It was concluded
      that there were different types of cut surface and attachment patterns of the
      acetabular labrum, and these findings had a tendency to be distributed with some
      labral tears. These anatomical data are believed could be useful in the
      management of an acetabular labral pathology.

PMID- 14584104
TI  - Dosimetric evaluation of the mean glandular dose for mammography in Korean women:
      a preliminary report.
AB  - The purpose of this study was to evaluate the thickness of the compressed breast
      in mediolateral oblique (MLO) and craniocaudal (CC) mammograms, to relate these
      thickness and breast patterns to mean glandular dose (MGD) in Korean women, and
      to evaluate the suitability of using the American College of Radiology's
      Recommendations for Korean women from a quality assurance standpoint. The study
      population consisted of 92 paired MLO and CC mammograms obtained on one
      mammographic unit. The digital readouts of compressed breast thickness, applied
      compression force and tube voltage were recorded. Entrance skin exposure was
      measured by dosimetry. MGD was calculated by multiplying entrance skin exposure
      by the exposure-to-absorbed dose conversion factor. The range of breast thickness
      was 1.3-6.2 cm in CC mammograms with a mean breast thickness of 3.6 cm, and 1.6
      6.5 cm in MLO mammograms with a mean breast thickness of 3.9 cm. MGDs in CC and
      MLO mammograms were 1.77 mSv and 1.88 mSv per view, respectively. Breast
      composition patterns were divided into 4 groups according to ACR BI-RADS; P1
      (n=20), P2 (n=16), P3 (n=48) and P4 (n=8). The MGDs for these groups were: 1.82,
      1.84, 1.84, and 1.91 mSv, respectively. When subjects were subdivided by breast
      thickness into three groups, namely, below 3 cm, 3 cm to 4.2 cm, aaa and above
      4.2 cm, the corresponding MGDs were 1.83, 1.86, and 1.91 mSv. According to our
      initial trial, the mean breast thickness and the MGDs of Korean women are lower
      than recommended by the American College of Radiology, which are commonly used
      for quality assurance purposes.

PMID- 14584105
TI  - Central Nomega-nitro-L-arginine methyl ester does not influence lithium-induced c
      Fos and conditioned taste aversion.
AB  - LiCl at doses sufficient to induce conditioned taste aversion (CTA) causes c-Fos
      expression in the brain regions implicated in CTA formation. It has been reported
      that nitric oxide (NO) may play a role in CTA learning and LiCl increases both
      the synthesis and activity of NO synthase (NOS) in the brain. In this study, we
      examined the effect of central Nomega-nitro-L- arginine methyl ester (L-NAME) on
      the brain c-Fos expression and CTA learning induced by lithium in rats. In the
      results, intracerebroventricular L-NAME given prior to lithium did not change
      either the lithium-induced CTA or c-Fos in the relevant brain regions. This
      suggests that the brain NO system may not be involved in the neuronal activation
      during lithium-induced CTA formation.

PMID- 14584106
TI  - Acculturation and cigarette smoking among Korean American men.
AB  - This study examined the prevalence and correlated factors of cigarette smoking in
      a cross-sectional, epidemiological survey of Korean American men living in
      Maryland (n=333). In this sample, 26.1% were current smokers and 42.3% were
      former smokers. The older age group (> or = 40 years) was more likely to have
      quit smoking than the younger age group (< 40 years). In multiple logistic
      regression analysis, acculturation was associated with smoking status; those who
      stayed more than 20 years in the U.S. were less likely to be current smokers
      (OR=0.32, 95% CI 0.13-0.77) than those who stayed less than 10 years. Alcohol use
      was associated with smoking status; those who consumed alcohol were more likely
      to be current smokers (OR=5.24, 95% CI 2.33-11.79) or former smokers (OR=5.45,
      95% CI=2.69-11.04) than those did not. Those with hypertension were more likely
      to have quit smoking (OR=3.11, 95% CI=1.33-7.24). The results suggest that the
      role of acculturation in smoking status among Korean American men deserves
      further attention by researchers as well as by health professionals who develop
      smoking prevention and cessation programs.

PMID- 14584107
TI  - Fall prevention exercise program for fall risk factor reduction of the community
      dwelling elderly in Korea.
AB  - A randomized comparison of pre-and post-experimental design was used to examine
      the effects of a fall prevention exercise program (FPEP) on muscle strength,
      ankle flexibility, balance, instrumental activities of daily living (IADLs), and
      depression for the community-dwelling elderly in Korea. Twenty-two subjects were
      assigned to an experimental group and twenty-three to a control group. The
      experimental group participated in a 4-day-per week FPEP of 8 weeks duration,
      twice a week by direct instruction and twice a week with videotaped instruction
      by the program instructor at each senior center. The eight-week FPEP turned out
      to be significantly effective in enhancing muscle strength, ankle flexibility and
      balance, and in reducing depression, after intervention among community-dwelling
      elderly in Korea. IADLs, however, was not changed by the intervention. Further
      research with a larger sample and longer follow up period is needed to expand our
      understanding about the effects of FPEP. Future study is also recommended to
      differentiate between the effects of FPEP by direct instruction and by
      videotaped.

PMID- 14584108
TI  - Development and validation of a computerized exercise intervention program for
      patients with type 2 diabetes mellitus in Korea.
AB  - This study was designed to develop and validate a computerized exercise
      intervention program using the transtheoretical model (TTM) for Korean patients
      with type 2 diabetes mellitus (DM). This computerized program was web-based and
      developed by designing a flow chart. An expert group (n=24), who validated the
      content of the computerized program, produced a mean score for the evaluation
      scale of 4.25 (SD.56). Of the patients (n=28) with type 2 DM who participated in
      clinical validity testing of the program, the mean score for the satisfaction
      scale was 4.82 (SD.12). In the validation of the program, significant differences
      between baseline and after-intervention were observed in the stage of readiness
      for exercise (Z=-3.78, p < 0.001), physical activity (Z=-2.33, p < 0.05), blood
      glucose profiles [FBS (Z=-2.84, p < 0.01), pc 2 hr. glucose (Z=-2.33, p < 0.05),
      HbA1c (Z=-2.77, p < 0.01)], and VO2max (Z=-2.52, p < 0.01). The study confirmed
      that the computerized program could be used to construct a database and continue
      to provide follow-up intervention for patients in all stages.

PMID- 14584109
TI  - Surgical experience of carotid pseudoaneurysm.
AB  - An extracranial carotid artery pseudoaneurysm is a rare condition that is caused
      by various types of arteritis, trauma and infectious causes. Generally, a
      pseudoaneurysm may be difficult to treat surgically when dissecting the
      paraaneurysmal fibrotic dense inflammatory tissues. The surgical management of a
      peudoaneurysm of the carotid artery involves a risk of nerve and arterial injury.
      This paper reports the repair of a carotid artery pseudoaneurysm after the
      proximal and distal control of the internal carotid artery using a Pruitt-Inahara
      shunt (P-I shunt) and the distal control of the external carotid artery using a
      small sized occlusion balloon catheter.

PMID- 14584110
TI  - Hemodynamical assessment of cavernous hemangioma in cavernous sinus using MR-DSA
      and conventional DSA.
AB  - We report a hemodynamical assessment of the blood turnover pattern as well as the
      imaging of cavernous hemangioma in a cavernous sinus using time-resolved contrast
      enhanced 2D projection MRA, also known as MR-DSA, and conventional digital
      subtraction angiography (DSA), before and after radiotherapy. MR-DSA showed very
      fast dynamical images of a contrast turnover pattern and was well matched with
      the findings obtained from DSA. MR-DSA is a non-invasive study, and can replace
      DSA in examining a vascular tumor for the initial work-up and follow-up
      examination.

PMID- 14584111
TI  - Ossified chronic subdural hematoma.
AB  - A relatively rare condition of ossified chronic subdural hematoma (SDH) mimicking
      cerebral stroke is presented. A 67-year-old man presented with headache,
      dysphasia, and left-sided hemiparesis. Routine skull x-ray showed a huge
      calcification extending from the frontal to the parietal regions in the right
      side. CT and MRI scan revealed a huge ossified SDH covering the right hemisphere.
      Right frontoparietal craniotomy was performed and the ossified SDH was completely
      removed. Severe adhesion was noticed between the pia mater and the inner surface
      of the ossified mass. The subdural mass had ossified hard outer and inner rims
      and a soft central part. The postoperative course was uneventful and 3 months
      after the operation, the patient was neurologically intact. The authors report
      the successful treatment of a patient with a huge ossified SDH covering the right
      hemisphere. Careful dissection and total removal are needed in such symptomatic
      cases to avoid cortical injury and to improve results.

PMID- 14584112
TI  - Modified submental orotracheal intubation using the blue cap on the end of the
      thoracic catheter.
AB  - The technique of submental intubation in patients with multiple facial fractures
      and skull base fracture was originally described by Altemir. This technique
      provides a secure airway and allows intermaxillary fixation while avoiding the
      complications of nasotracheal intubation or tracheostomy. However, when the
      endotracheal pilot balloon and endotracheal tube are pulled through the submental
      incision site using this technique, soft tissues or blood may enter the
      endotracheal tube and trauma may result in the surrounding tissues. To overcome
      these problems, we carried out a modification of submental orotracheal intubation
      using the blue cap on the end of the thoracic catheter in a patient with
      mandibular fractures and injury to the skull base and found that this
      modification resulted in a safer and less traumatic intubation.

PMID- 14584113
TI  - Inherited vitamin K deficiency: case report and review of literature.
AB  - Vitamin K is the cofactor for the hepatic carboxylation of glutamic acid residues
      in a number of proteins including the procoagulants factors II, VII, IX, and X.
      The role of vitamin K in normal bone function is not fully understood. Inherited
      deficiency of vitamin K dependent coagulation factors is a rare bleeding disorder
      reported only in a few patients. Here we present an 18-month old child who
      presented with osteopeni due to inherited vitamin K deficiency. While the patient
      had high bone specific alkaline phosphatase and parathyroid hormone levels and
      low osteocalcin and bone mineral density values, with the regular supplementation
      of vitamin K all the mentioned parameters returned to normal values.

PMID- 14584114
TI  - Erythrophagocytosis by myeloid cells in a patient with myeloproliferative
      disorder.
AB  - This report documents a case of myeloid erythrophagocytosis in a patient with
      myeloproliferative disorder. The patient had pancytopenia and his marrow was
      hyperplastic with erythrophagocytosis by myeloid cells of various stages,
      including myeloblasts. He was diagnosed to have a prefibrotic stage of chronic
      idiopathic myelofibrosis. The erythrophagocytosis by myeloid cells persisted even
      after 2 months of treatment for the primary disorder.

PMID- 14584115
TI  - A Korean case of anti-p200 pemphigoid.
AB  - Anti-p200 pemphigoid is a newly defined autoimmune subepidermal blistering
      disease, which is characterized by the presence of IgG autoantibodies to the
      dermal side of 1 M NaCl split skin as well as by the reactivity of these
      antibodies to a novel 200-kDa antigen on immunoblot analysis of a dermal extract.
      We describe a 49-year-old Korean male who presented with a bullous eruption on
      the whole body, which clinically resembled bullous pemphigoid or epidermolysis
      bullosa acquisita. A histopathological examination of a lesional skin biopsy
      specimen showed an area of dermal-epidermal separation and mixed dermal
      inflammatory infiltrates consisting of lymphocytes, neutrophils, and eosinophils.
      Direct immunofluorescence showed a linear deposition of IgG and C3 along the
      basement membrane zone. Indirect immunofluorescence demonstrated circulating IgG
      autoantibodies directed against the dermal side of the 1 M NaCl split skin.
      Immunoblot analysis of dermal extracts revealed the patient's sera recognized the
      200-kDa antigen. This is the first Korean case of an anti-p200 pemphigoid who
      showed good response to the treatment with systemic corticosteroids and dapsone.

PMID- 14584116
TI  - Behcet's disease: the first Mongolian case in literature showing HLA B51, MICA
      gene type *5/*6.
AB  - Behcet's disease is a chronic multi-systemic disease of unknown origin that
      includes mucocutaneous, ocular, cardiac, vascular, renal, gastrointestinal,
      neurologic and cutaneous involvement. The disease is spread throughout the world,
      but it is most prevalent in the eastern Mediterranean region-along the Silk Road
      , and in Japan, China, and Korea. Recently, we treated a Mongolian patient who
      had complete-type Behcet's disease. As far as we know, this case is the first
      report of a Mongolian with Behcet's disease in the English literature. HLA typing
      in this patient revealed A2, A24;B51, B35; Cw4, Cw7; DR9, DR11. Study of the MICA
      genetype showed *5, *6 positive. Our data provided adequate evidence, from an
      epidemiological aspect, to support the belief that Behcet's disease is most
      prevalent along the old Silk Road.

PMID- 14584117
TI  - An unusual combination of relapsing and cholestatic hepatitis A in childhood.
AB  - Clinical variants of hepatitis A include the prolonged, relapsing and cholestatic
      forms. Here, the first childhood case of hepatitis A, with a combination of the
      relapsing and cholestatic forms is presented, a 14-year old boy. In the first
      phase of the illness, while the AST and ALT levels were declined, th total and
      direct bilirubin and GGT were increased. The patient was thought to have the
      cholestatic form of hepatitis A. Du to intense pruritus and high bilirubin
      levels, ursodeoxycholic acid (UDCA) therapy was started. On the 17th day, the
      decreased AST and ALT levels began to increase, reaching levels as high as 484
      U/L and 862 U/L, respectively. The UDCA treatment was stopped on the 64th day. On
      the 164th day, all his laboratory parameters were within normal limits, but the
      anti-HAV IgM was still positive.

PMID- 14584118
TI  - Ruptured renal artery stump aneurysm in a renal autotransplanted Behcet's disease
      patient.
AB  - A recurrent aneurysm at the anastomosis site or the remaining artery frequently
      occurs after the operative treatment of an aneurysm in Behcet's disease despite
      anti-inflammatory medication. Herein, a ruptured left renal artery stump aneurysm
      in a patient with Behcet's disease, who received a left nephrectomy, aorto
      biiliac bypass and heterotopic autotransplantation of the right kidney for the
      treatment of an abdominal aortic aneurysm and renal hypertension one year prior
      to this admission, is reported. An aneurysm and rupture occurred despite the
      administration of anti-inflammatory medications while monitoring of the clinical
      findings, such as skin manifestations, erythrocyte segmentation rate (ESR) and C
      reactive protein (CRP). Although there is no definite proven treatment modality
      to prevent recurrent aneurysms at the anastomosis site or a remote artery, close
      follow-up with anti-inflammatory medications, and surveillance with regular
      intervals are the only current methods for the prevention and/or to treatment of
      an arterial complication in patients with Behcet's disease.

PMID- 14584120
TI  - [Poisonous and less poisonous plants. 53].

PMID- 14584119
TI  - [The infection susceptible child. What is necessary, what can be omitted?].

PMID- 14584121
TI  - [Interdisciplinary treatment concepts for patients with HIV infection].

PMID- 14584122
TI  - [Nursing care priorities in managing HIV-positive children and their parents].

PMID- 14584124
TI  - [Extracorporeal membrane oxygenation (ECMO) in newborn infants].

PMID- 14584123
TI  - [Shock for life--early defibrillation by lay persons with AED equipment].

PMID- 14584125
TI  - [Binasal CPAP as an alternative to tracheal tube].

PMID- 14584126
TI  - [Significance of spontaneous motor activity and visual information processing for
      developmental diagnosis in infancy].
AB  - The neurodevelopmental examination during the first years of life is very often
      confronted with the problem of differentiating between normal variability and
      pathology of development. Recent research provides evidence about the clinical
      relevance of the systematic observation and examination of spontaneous movements,
      of postural control as well as of visual information processing in toddlers.

PMID- 14584127
TI  - [Trends in nursing care in pediatric oncology].

PMID- 14584128
TI  - [Pediatric nursing on the internet].

PMID- 14584129
TI  - [The current reimbursement system and future DRG system compared].

PMID- 14584130
TI  - [Pediatric home care nursing of an infant with trisomy 13 (Patau syndrome)].

PMID- 14584131
TI  - [Illness perception of a patient with Guillain-Barre syndrome].

PMID- 14584132
TI  - [Intercultural communication in the hospital--on communication between nurses and
      immigrant patients].

PMID- 14584133
TI  - [Talking with children about death].

PMID- 14584134
TI  - [Better outcome for premature infants through NIDCAP].

PMID- 14584135
TI  - [Integration of the basal stimulation concept in routine nursing care].

PMID- 14584136
TI  - [ADHS--a fad diagnosis or challenge in our time].

PMID- 14584137
TI  - [Anthrax. Basic principles and preventive measures].

PMID- 14584138
TI  - [Education of the TQM specialist in social and public health--a path into the
      future for pediatric nurses and midwives?].

PMID- 14584139
TI  - [Wound protection for delicate baby and children's skin. 3M Cavilon non
      irritating skin protection in pediatrics].

PMID- 14584140
TI  - [Breast feeding in the maternity clinic and in the 1st year of life: results of
      the comprehensive country-wide SuSe Study].

PMID- 14584141
TI  - [Contribution of nursing to breast and human milk feeding in neonatology].

PMID- 14584142
TI  - [Child health--prevention by parent education--a study area for pediatric
      nurses].

PMID- 14584143
TI  - [Poisonous and less poisonous plants. 55].

PMID- 14584144
TI  - [Thoughts on preimplantation techniques].

PMID- 14584145
TI  - [Nursing reformulation--on the future of nursing education].

PMID- 14584146
TI  - [Nursing theories for nurses and nursing care in puerperium].

PMID- 14584147
TI  - [Historical and psychological personality aspects of the maternal role].

PMID- 14584148
TI  - [Malpractice law: what should be learned].

PMID- 14584149
TI  - [Comment on the article on "Significance of psychosocial aspects in nursing and
      nursing care of children with burn injuries" by Sandra Pfeil].

PMID- 14584150
TI  - [Jonas and Lukas].

PMID- 14584151
TI  - [Experiences with the use of child and adolescent psychiatry as a student].

PMID- 14584152
TI  - [3rd Childood Celebration of the Cottbus Premature Infant Society. A resume of 3
      years existence].

PMID- 14584153
TI  - [Sudden infant death--a solution in sight?].

PMID- 14584154
TI  - [A correlation between sudden infant death (SIDS) and Helicobacter pylori
      infection? Transmission of the bacterium by kissing the baby is highly unlikely].

PMID- 14584155
TI  - [The long road to nursing diagnoses in child and adolescent nursing].

PMID- 14584156
TI  - [Physical therapy techniques with infants and school children with primary
      ciliary dyskinesia (Kartagener syndrome)].

PMID- 14584157
TI  - [Nursing plan for a severely mentally, psychomotor and statomotor retarded
      child].

PMID- 14584158
TI  - ["Touch stimulates--stimulation touches". International Basal Stimulation
      Congress].

PMID- 14584159
TI  - [Poisonous and less poisonous plants. 54].

PMID- 14584160
TI  - [Overwhelmingly positive aspects of the pacifyer].

PMID- 14584161
TI  - [The life and contributions of Hildegard von Bingen].

PMID- 14584162
TI  - [Holistic patient management of chronically ill children in the pediatric
      rehabilitation clinic of the Wangen Specialty Clinic. Interdisciplinary
      cooperation of child rearing specialists and pediatric nurses].

PMID- 14584164
TI  - [Naturopathy in pediatric nursing. Project description].

PMID- 14584163
TI  - [22nd Congress of the International Council of Nurses 10 to 15 June in
      Copenhagen].

PMID- 14584165
TI  - [Family-oriented pediatric nursing. The Marie-Luise Friedman model of family- and
      environment-oriented nursing and relevance for education].

PMID- 14584166
TI  - [Normality in daily routine. A qualitative study of home-based pediatric nursing
      in Berlin].

PMID- 14584167
TI  - [Emergency on the pediatric oncologic unit--from the viewpoint of the nurses].

PMID- 14584168
TI  - [Accidental trauma of a child. Effects on the family].

PMID- 14584169
TI  - [Closed endotracheal suction in pediatric and neonatal intensive care nursing].

PMID- 14584170
TI  - [The significance of psychosocial aspects of nursing and management of the child
      with burns].

PMID- 14584171
TI  - [Promoting breast feeding in hospitals].

PMID- 14584172
TI  - [Family-oriented nursing in home management of chronically ill children-
      perspectives of a family and a nurse].

PMID- 14584173
TI  - [Collection of peripheral hematopoietic stem cells in pediatric oncology].

PMID- 14584175
TI  - [Guidelines for an anthroposophic hospital].

PMID- 14584174
TI  - [Poisonous and less poisonous plants. 52].

PMID- 14584176
TI  - [Pulmarca Box. Is artificial respiration with continuous negative pressure (CNP)
      still current today?].

PMID- 14584178
TI  - [Bereaved siblings. How to help grieving children?].

PMID- 14584179
TI  - The value of association vs value of the association.

PMID- 14584177
TI  - [Psychosocial adaptation and compliance in chronic diseases in childhood].
AB  - A chronic disease in childhood often entails multidimensional, medical,
      psychosocial and financial risks which empede efficient adaptation to the disease
      for the whole family. Aim of this review is to describe possible strategies for
      effective coping with the chronic disease with the main focus on self-help
      competence for the affected child and his family. Furthermore, there are
      proposals regarding practical handling of therapeutical noncompliance in the
      chronically ill infant. The family of a child with a chronic disease often
      contacts nurses for further, non-medical information. Therefore the aim of the
      review is to inform nurses of the biopsychosocial risks and consequences for
      every day life as well as to provide them with supportive self-help-strategies of
      the affected family.

PMID- 14584180
TI  - Accessibility standards and your Website.

PMID- 14584181
TI  - OPL--a solo librarian's peak experience.

PMID- 14584182
TI  - Making the most of Docline.

PMID- 14584183
TI  - [Mad in Germany. Mad cow disease and it's sequelae].

PMID- 14584184
TI  - [BSE mad cow disease--assessment of current status. Results of a Journalist
      Seminary of DGE "Eating and Drinking in 2000" in Fulda 17th-18th January 2001].

PMID- 14584185
TI  - [Therapy of traumatic pancreatic rupture/pseudocyst with sandostatin and external
      catheter drainage].

PMID- 14584186
TI  - [Catecholamines. Basic and nursing relevant problems].

PMID- 14584187
TI  - [Female behavior--biology or tradition?].

PMID- 14584188
TI  - [A special day in education. A theatrical presentation of the status of the child
      in different epoches].

PMID- 14584190
TI  - California bonanza? Providers and insurers cheer mandatory health insurance law,
      but business interests look at legal challenge to newly signed bill.
AB  - Consider it Gov. Gray Davis' going-away present to the state's hospitals,
      insurers and physician groups. The California Health Insurance Act of 2003 could
      mean increased revenue for hospitals. Doctors like Brian Johnston, left, say the
      bill has been a long time coming and are pleased with the legislation, but others
      are concerned about what effects the mandatory insurance law will have on small
      businesses.

PMID- 14584189
TI  - [Preventing iodine deficiency in pregnancy and breast feeding. Passivity means
      health risks for mother and child].

PMID- 14584191
TI  - Joining forces. Network creates a lower-cost insurance plan for docs.

PMID- 14584192
TI  - HIPAA unplugged. Troublesome burden of claim transactions sidetracks progress in
      adopting other cost-cutting standards.

PMID- 14584194
TI  - Doc surplus no more. Panel tells medical schools to increase enrollment.

PMID- 14584193
TI  - Volunteer or else. Scully threatens mandatory quality reporting.

PMID- 14584195
TI  - Spreading its wings. Indiana system shares surgery center expertise.

PMID- 14584196
TI  - CON conflict. HMA wins Fla. OK but still may face hurdle.

PMID- 14584197
TI  - Time for a change. Current payer systems must be overhauled to reduce complexity,
      costs.

PMID- 14584198
TI  - A piece of the action. Service-line joint ventures between hospitals and medical
      groups are taking partnerships to a whole new level.

PMID- 14584199
TI  - With bated breath. Though Medicare will begin reimbursing for surgery to aid some
      emphysema patients, questions remain over benefit, cost.

PMID- 14584200
TI  - [Raised calcium level but no symptoms. Would you send this patient to surgery?].

PMID- 14584201
TI  - [Medication errors. Cause of death for every 100th hospital patient? (interview
      by Dr. Thomas Meissner)].

PMID- 14584202
TI  - [Purulent infection, severe swelling, dyspnea. When does bee sting become an
      emergency? (interview by Dr. Judith Neumaier)].

PMID- 14584203
TI  - [Asthma after summer thunderstorm, stroke in cold weather, death in heat. When
      weather causes illness].

PMID- 14584204
TI  - [Coronary patients in change of seasons. How heat and cold affect myocardial
      infarct].

PMID- 14584205
TI  - [Temperature drop, the common cold, high humidity. Triggers for stroke].

PMID- 14584206
TI  - [Not good for weak veins. Winter temperature promote thrombus formation].

PMID- 14584207
TI  - [Asthma attack after summer thunderstorm. How rain storms and temperature drops
      affect the respiratory tract].

PMID- 14584208
TI  - [Fever after (sub-) tropical vacation. Harmless virus or dangerous malaria?].

PMID- 14584209
TI  - [Therapeutic management of problem wounds. Moist wound management is the
      nonplusultra].

PMID- 14584210
TI  - [Psychosocial treatment plus drug prophylaxis. Fewer recurrences after alcohol
      withdrawal].

PMID- 14584211
TI  - [Therapy of erectile dysfunction. Hard facts support sildenafil].

PMID- 14584213
TI  - [Provide motivation for cardiovascular disease prevention. Nonsmokers are have
      better sexual performance].

PMID- 14584212
TI  - [In sex dysfunctions--not just a "male issue". Don't forget women].

PMID- 14584214
TI  - [Dangerous blood glucose peaks. Vascular damage even before diabetes].

PMID- 14584215
TI  - [New drug class blocks virus-cell fusion. HIV not admitted].

PMID- 14584216
TI  - [Homeopathy and behavior therapy. Gentle duo against sleepless nights].

PMID- 14584217
TI  - [Conservative use of antibiotics is important, but: "Resistance hysteria is
      exaggerated"].

PMID- 14584218
TI  - [Successful therapy with pegylated interferon alfa-2a. Hepatitis C patients
      remain virus-free].

PMID- 14584219
TI  - [How does this work? Capsule endoscopy].

PMID- 14584221
TI  - [Diagnosis at a glance. Telangiectasias requiring transfusions].

PMID- 14584220
TI  - [10 minute consultation. Acute tonsillitis].

PMID- 14584222
TI  - Can the grocer provide pharmaceutical care?

PMID- 14584223
TI  - Accessing medication information by ethnic minorities: barriers and possible
      solutions.
AB  - AIM: This review discusses two main questions: how suitable is current consumer
      medication information for minority ethnic groups, and what are effective
      strategies to overcome existing barriers. The focus is on minority groups whose
      first language is not the language of the healthcare system. METHOD: We searched
      electronic databases and printed scientific journals focusing on (ethnic)
      minorities, health and/or (intercultural) communication. We also asked a
      discussion group for references. RESULTS: We found only a few articles on
      intercultural communication on medication or pharmacy information and one article
      on the improvement of intercultural communication in the pharmacy. Barriers to
      the access of medication information by ethnic minorities include second language
      issues and cultural differences due to different health beliefs, together with
      the low socio-economic status often seen among ethnic minorities. Cultural
      differences also exist among different socio-economic classes rather than only
      among ethnic groups. Most often, informal interpreters are used to improve
      intercultural communication. However, this may result in miscommunication due to
      a lack of medical knowledge or training on the part of the interpreter. To
      minimise miscommunication, bilingual health professionals or health
      interpreters/advocates can be used, although communication problems may still
      occur. The effectiveness of written information depends on the literacy skills of
      the target population. Cultural, medical and dialect biases should be avoided by
      testing the material. Multimedia systems may be alternatives to conventional
      written information. DISCUSSION: Barriers that ethnic minorities face in
      accessing medication information and possible solutions involving counselling and
      additional tools were identified for pharmacy practice. However, more research is
      needed to develop effective strategies for patient counselling in pharmacy to
      meet the needs of ethnic minorities.

PMID- 14584224
TI  - Patient sources of drug information and attitudes to their provision: a
      corticosteroid model.
AB  - AIM: To determine patient's preferred sources of drug information and their
      attitudes to how this is provided. DESIGN: A quantitative evaluation via personal
      interviews using a formal questionnaire. SUBJECT AND SETTINGS: A group of 101 in
      patients in a chest ward at the Royal Devon & Exeter Healthcare NHS Trust.
      OUTCOME MEASURES: Preferred sources for medication advice; personal involvement
      in own treatment; adequacy of consultation period; medication compliance; post
      discharge sources of drug information; recalled benefits and side effects of
      corticosteroids. RESULTS: Preferred source of drug information was: doctor (35%),
      pharmacist (11%) and nurse 4%. Sixty percent of patients wanted to be involved in
      the choice of their medication, thirty-nine percent leaving it totally to the
      doctor and one patient who wanted the final word in what was prescribed.
      Sufficient discussion time with GPs was reported by 66% of patients (12%,
      insufficient) and 53% with hospital doctors (19%, insufficient). Non-compliance
      with medication was reported by 66% and compliance by 24%. Medication advice
      sources used when at home were; community pharmacists (22%), GPs/books &
      magazines/specialist societies (all 18%), nurses (10%) and others less than 8%.
      Benefits of corticosteroids recalled by patients were: 'improving breathing'
      (14), 'general improvement' (9) and 'improved mobility'/'greater appetite' (both
      5)' with little change' reported by 13. Knowledge of side effects was much more
      comprehensive with; oedema/weight gain (50), skin/hair problems (33),
      osteoporosis (33), bruising (12) and mood changes (10) most commonly featured in
      responses. Almost all patients confirmed they liked to be given printed
      information about their medication. CONCLUSION: Patients sought their medication
      advice from a variety of sources and armed with this almost two thirds of
      patients wished to exercise their rights to be involved with their treatment
      planning. Sufficient discussion time appeared to be available to about half of
      the interviewees though only a few understood the intended benefits of prescribed
      corticosteroids used as an example in this work. A much better knowledge of drug
      side effects might have partly explained the high level of declared non
      compliance. Although pharmacists featured as the preferred source of drug
      information for some patients, a much more detailed investigation is needed of
      patients' attitudes to the profession and to individuals' consultation and
      communication skills.

PMID- 14584225
TI  - Opinion and behaviour of pharmacists towards the substitution of branded drugs by
      generic drugs: survey of 1,000 French community pharmacists.
AB  - OBJECTIVE: In 1999, a new law was introduced, giving French pharmacists the right
      to switch from branded to generic drugs, unless the prescriber had specified that
      substitution was not permitted. The purpose of this study was to assess the
      opinion and behaviour of community pharmacists toward substitution. DESIGN: Self
      completion, postal close-ended questionnaires were filled out. SAMPLE AND
      SETTING: 1,000 French community pharmacists were included. RESULTS: 90% of the
      pharmacists were favourable to the implementation of the substitution right.
      42.5% declared they systematically offered patients the generic drug, whereas 55%
      chose to target specific populations for substitution. The reluctance of
      pharmacists could be commercial ('How do I get paid for the time spent? Is it
      worth risking loosing a customer?'), or cultural ('How do I work this out? Who
      should I offer generic drugs to? What strategy should I use to offer them?').
      CONCLUSION: Generic drug distribution is very recent in France and is not yet
      common practice. Pharmacists and patients must be informed and trained because
      substitution is a collaborative act. It does not depend solely on the will and
      experience of pharmacists.

PMID- 14584226
TI  - Socio-economic differences in prescription and OTC drug use in Dutch adolescents.
AB  - OBJECTIVE: To detect whether there were socio-economic differences in the overall
      use of prescription and OCT drugs among adolescents. METHODS: This study was a
      secondary analysis of questionnaire data collected to investigate socio-economic
      differences in health risk behaviour and decision-making. RESULTS: About 20% of
      the 741 girls and 10% of the 736 boys reported using at least one prescription
      drug in the past 14 days, oral contraceptives excluded. For OTC drugs these
      percentages were 45% and 24%, respectively. No statistically significant socio
      economic differences in prescription drug use could be detected. A higher socio
      economic status was associated with an increased OTC drug use, especially in
      boys. The odds of girls who reported medication was about twice that for boys,
      after adjusting for perceived health and socio-economic status. CONCLUSION: There
      were socio-economic differences with regard to OTC drug use. No socio-economic
      differences in prescription medication use could be found. There were gender
      differences with respect to medication use in adolescence, regardless of
      perceived health and socio-economic status.

PMID- 14584227
TI  - Determinants for successful smoking cessation with bupropion in daily practice.
AB  - OBJECTIVE: To describe the patterns of use of bupropion in daily clinical
      practice and factors which determine successful smoking cessation. METHODS:
      Retrospective follow-up study in 36 pharmacies in the Netherlands. Patients who
      received at least one prescription for bupropion between January and April, 2000
      were included. The pharmacists noted several characteristics relating to the
      patient, use of bupropion and co-medication. Patients were interviewed by
      telephone about their current and former smoking habits, the success of their
      smoking cessation and their experiences with bupropion. MAIN OUTCOME MEASURE:
      Abstinence rate and factors determining successful abstinence after six months.
      RESULTS: 322 patients with a least one prescription for bupropion were
      identified. In 93.5% of patients bupropion was prescribed by the general
      practitioner. Half of the patients were dispensed 30 or fewer tablets.
      Pharmacists interviewed 215 (66.8%) patients by telephone. Of these patients 58
      (27.0%) still did not smoke six months after the prescription for bupropion. The
      number of tablets used, lack of co-morbidity, less than two previous attempts to
      stop smoking and private-insurance were associated with a higher rate of
      successful abstinence. CONCLUSION: Most patients do not use bupropion in
      accordance with the recommended period and did not receive the same degree of
      additional support provided in clinical trials. Nevertheless 27.0% of patients
      reported to have stopped smoking six months after the prescription for bupropion.
      This self-reported abstinence rate is only slightly lower than is reported in
      literature. This might be partly related to the fact that we did not validate
      smoking cessation by carbonmonoxide monitoring. Bupropion is not reimbursed in
      the Netherlands. It is difficult to assess whether patients' self-payment has led
      to the selection of motivated patients, or has been a barrier to finishing using
      bupropion.

PMID- 14584228
TI  - Development of a quality use of medicines coding system to rate clinical
      pharmacists' medication review recommendations.
AB  - OBJECTIVE: To develop a 'quality use of medicines' coding system for the
      assessment of pharmacists' medication reviews and to apply it to an appropriate
      cohort. METHOD: A 'quality use of medicines' coding system was developed based on
      findings in the literature. These codes were then applied to 216 (111
      intervention, 105 control) veterans' medication profiles by an independent
      clinical pharmacist who was supported by a clinical pharmacologist with the aim
      to assess the appropriateness of pharmacy interventions. The profiles were
      provided for veterans participating in a randomised, controlled trial in private
      hospitals evaluating the effect of medication review and discharge counselling.
      The reliability of the coding was tested by two independent clinical pharmacists
      in a random sample of 23 veterans from the study population. MAIN OUTCOME
      MEASURE: Interrater reliability was assessed by applying Cohen's kappa score on
      aggregated codes. RESULTS: The coding system based on the literature consisted of
      19 codes. The results from the three clinical pharmacists suggested that the
      original coding system had two major problems: (a) a lack of discrimination for
      certain recommendations e.g. adverse drug reactions, toxicity and mortality may
      be seen as variations in degree of a single effect and (b) certain codes e.g.
      essential therapy were in low prevalence. The interrater reliability for an
      aggregation of all codes into positive, negative and clinically non-significant
      codes ranged from 0.49-0.58 (good to fair). The interrater reliability increased
      to 0.72-0.79 (excellent) when all negative codes were excluded. Analysis of the
      sample of 216 profiles showed that the most prevalent recommendations from the
      clinical pharmacists were a positive impact in reducing adverse responses
      (31.9%), an improvement in good clinical pharmacy practice (25.5%) and a positive
      impact in reducing drug toxicity (11.1%). Most medications were assigned the
      clinically non-significant code (96.6%). In fact, the interventions led to a
      statistically significant difference in pharmacist recommendations in the
      categories; adverse response, toxicity and good clinical pharmacy practice
      measured by the quality use of medicine coding system. CONCLUSION: It was
      possible to use the quality use of medicine coding system to rate the quality and
      potential health impact of pharmacists' medication reviews, and the system did
      pick up differences between intervention and control patients. The interrater
      reliability for the summarised coding system was fair, but a larger sample of
      medication regimens is needed to assess the non-summarised quality use of
      medicines coding system.

PMID- 14584229
TI  - Community pharmacy based provision of pharmaceutical care to older patients.
AB  - AIM: To measure the outcomes of a harmonized, structured pharmaceutical care
      programme provided to elderly patients by community pharmacists. METHOD: A
      randomised, controlled, longitudinal, clinical trial with repeated measures was
      performed over an 18-month period, involving community pharmacies (5 intervention
      and 5 control) in Northern Ireland. Elderly, ambulatory patients (> or = 65
      years), taking 4 or more prescribed medications were eligible for participation.
      Patients attending an intervention pharmacy received education on medical
      conditions, implementation of compliance strategies, rationalizing of drug
      regimens and appropriate monitoring; patients attending control sites received
      normal services. A battery of clinical, humanistic and economic outcomes were
      assessed. RESULTS: A significantly higher proportion of intervention patients
      were compliant at the end of the 18-month study and experienced fewer problems
      with medication compared to control patients (P < 0.05). There was little impact
      on quality of life and health care utilisation. CONCLUSIONS: Pharmaceutical care
      provision to community-dwelling patients resulted in an improvement in medication
      compliance and evidence of cost-savings. Future pharmaceutical care studies may
      benefit from a more focussed selective approach to data collection and outcomes
      measurement.

PMID- 14584230
TI  - Understanding practice change in community pharmacy: a qualitative research
      instrument based on organisational theory.
AB  - INTRODUCTION: The past decade has seen a notable shift in the practice of
      pharmacy, with a strong focus on the provision of cognitive pharmaceutical
      services (CPS) by community pharmacists. The benefits of these services have been
      well documented, yet their uptake appears to be slow. Various strategies have
      been developed to overcome barriers to the implementation of CPS, with varying
      degrees of success, and little is known about the sustainability of the practice
      changes they produce. Furthermore, the strategies developed are often specific to
      individual programs or services, and their applicability to other CPS has not
      been explored. There seems to be a need for a flexible change management model
      for the implementation and dissemination of a range of CPS, but before it can be
      developed, a better understanding of the change process is required. OBJECTIVES:
      This paper describes the development of a qualitative research instrument that
      may be utilised to investigate practice change in community pharmacy. Specific
      objectives included gaining knowledge about the circumstances surrounding
      attempts to implement CPS, and understanding relationships that are important to
      the change process. METHODS: Organisational theory provided the conceptual
      framework for development of the qualitative research instrument, within which
      two theories were used to give insight into the change process: Borum's theory of
      organisational change, which categorizes change strategies as rational, natural,
      political or open; and Social Network Theory, which helps identify and explain
      the relationships between key people involved in the change process. RESULTS: A
      semi-structured affecting practice change found in the literature that warranted
      further investigation with the theoretical perspectives of organisational change
      and social networks. To address the research objectives, the instrument covered
      four broad themes: roles, experiences, strategies and networks. CONCLUSION: The
      qualitative research instrument developed in this study provides a starting point
      for future research to lead to a description and understanding of practice change
      in community pharmacy, and subsequent development of models for the sustainable
      implementation of CPS.

PMID- 14584231
TI  - Changing relationships: attitudes and opinions of general practitioners and
      pharmacists regarding the role of the community pharmacist.
AB  - BACKGROUND: Relationship between general practitioners and pharmacists. AIM: To
      explore similarities and differences in opinions between general practitioners
      and pharmacists about the pharmacist's role. To identify factors which determine
      the attitude of the general practitioner towards the role of the pharmacist as a
      care provider. DESIGN: Cross-sectional questionnaire survey. SETTING: The
      Netherlands, 2001. PARTICIPANTS: 926 non-dispensing general practitioners, 93
      dispensing general practitioners and 328 community pharmacists. METHODS:
      Statements about the pharmacist's position in primary care were formulated. The
      attitude towards the pharmacist's care-providing function was determined by
      adding the scores to the statements. Data were collected on age, gender,
      professional experience, trainership, type and size of practice, electronic
      communication, urbanisation level, part-time work, work pressure, postgraduate
      training, pharmacotherapy audit meetings (PTAMs), the mutual relationship and the
      desired role of the pharmacist in pharmacotherapy. RESULTS: No significant
      differences in opinions were found between pharmacists and non-dispending general
      practitioners with respect to a number of the pharmacist's signalling tasks.
      Eighty-six percent (CI 83-89) of non-dispensing general practitioners and eighty
      two percent (CI 76-87) of pharmacists shared the opinion that pharmacists need to
      provide the general practitioner with feedback on prescription figures.
      Furthermore, 85% (CI 82-88) of the non-dispensing general practitioners and 80%
      (CI 75-86) of the pharmacists believed that pharmacists should suggest items for
      the PTAM agenda, based on prescription patterns they notice in their pharmacy.
      The attitude of general practitioners towards the care-providing function of the
      community pharmacist correlates significantly with the relationship between
      general practitioners and pharmacists (P < 0.001). There is also a significant
      difference (P < 0.001) in the attitude score between dispensing and non
      dispensing general practitioners: dispensing general practitioners scored lower
      on the attitude scale. CONCLUSION: Pharmacists and general practitioners largely
      agree on the pharmacotherapeutic signalling role that a pharmacist should
      fulfill. A good relationship benefits the attitude of general practitioners
      towards the pharmacist's care-providing function.

PMID- 14584232
TI  - False-positive acetaminophen results in hyperbilirubinemic patients with an
      enzymatic colorimetric assay.

PMID- 14584233
TI  - The evidence base on the orthopaedic NICE report.

PMID- 14584234
TI  - The future health-care worker: health-care practitioner.

PMID- 14584235
TI  - Huntington's disease of early onset or juvenile Huntington's disease.
AB  - The presentation of juvenile Huntington's disease can cause diagnostic
      difficulties. The genetics and pathogenesis of the condition are discussed. The
      diagnosis will depend on the symptoms raising suspicions and the exclusion of
      other disorders, especially by genetic studies.

PMID- 14584236
TI  - Does trauma trigger multiple sclerosis? 1: A controversy.
AB  - The potential role of trauma in the development of multiple sclerosis is
      important but controversial. Patients commonly ask about this and it has
      important medicolegal ramifications. In addressing such issues this article will
      consider both physical and psychological trauma, examine pathogenic mechanisms,
      and discuss the evidence for and against a relationship.

PMID- 14584237
TI  - Progressive supranuclear palsy.
AB  - Progressive supranuclear palsy, also known as Steele-Richardson-Olszewski
      syndrome, is an uncommon neurodegenerative parkinsonian disorder that starts in
      middle and late life, and is frequently misdiagnosed as Parkinson's disease. This
      review will cover the epidemiology, clinical picture, differential diagnosis and
      management of patients with progressive supranuclear palsy.

PMID- 14584238
TI  - Cialis (tadalafil): a new treatment for erectile dysfunction.
AB  - Oral phosphodiesterase inhibitors have become the mainstay of treatment for
      erectile dysfunction. A novel and potent phosphodiesterase inhibitor, tadalafil,
      known as Cialis, has been introduced in the UK as an alternative to the other
      currently available phosphodiesterase inhibitors for the treatment of erectile
      dysfunction.

PMID- 14584239
TI  - Venous stasis syndrome: the long-term burden of deep vein thrombosis.
AB  - Currently there is no cure for venous stasis syndrome, a common complication of
      deep vein thrombosis. Prophylaxis with anticoagulant agents, including new drugs
      presently under investigation, may decrease the incidence and costs associated
      with this condition.

PMID- 14584241
TI  - The long-acting depot antipsychotic drugs.
AB  - The novel antipsychotics have reduced the use of depot medications, but the
      introduction of the atypical depot antipsychotic has rekindled an interest in the
      long-acting antipsychotic formulations. The use of atypical antipsychotics is
      recommended, except where patients are otherwise stable on classical
      antipsychotics without unwanted side effects.

PMID- 14584240
TI  - The genetics of inflammatory bowel disease.
AB  - Over the past 10 years major progress has been made in understanding the genetic
      contribution to inflammatory bowel disease. NOD2 was recently identified as a
      major susceptibility gene for Crohn's disease. This and a number of other strong
      genetic leads are discussed.

PMID- 14584242
TI  - The eye in metabolic disease.

PMID- 14584244
TI  - Laying the foundations for good medical practice: a new educational resource.
AB  - Balancing service commitments with educational development is never easy. The
      European Working Time Directive and the Chief Medical Officer's report on senior
      house officer training bring new challenges. The Royal College of Physicians has
      developed 'Laying the Foundations for Good Medical Practice', a resource that
      enables tutors to teach generic skills to small groups of trainees in a fun and
      interactive way.

PMID- 14584243
TI  - Antibiotic-loaded cement in revision joint replacement.
AB  - The infected joint replacement remains a difficult clinical challenge. Antibiotic
      loaded cement provides one therapeutic solution that combines mechanical
      stability and antibiotic delivery.

PMID- 14584245
TI  - An acute disseminated encephalomyelitis-like illness following alcohol
      withdrawal.

PMID- 14584247
TI  - Guidelines are not directives.

PMID- 14584246
TI  - Thyroid abscess: an unusual case secondary to biliary sepsis.

PMID- 14584248
TI  - Difficult hyponatraemia in an elderly woman.

PMID- 14584249
TI  - Sevoflurane or halothane for induction in acute airway emergencies in children?

PMID- 14584250
TI  - [Depressive tendency, self-focused attention, and self-referent processing of
      personality trait adjectives].
AB  - The purpose of this study was to examine the interaction effect of depressive
      tendency and self-focused attention on self-referent processing of personality
      trait adjectives. Pairs of adjectives were used; they were similar in meaning,
      but one was positive in desirability, while the other negative. Sixty
      undergraduates, 30 mildly depressed and 30 normal controls, participated in the
      study. Only the self-focus group was first given a self-focus sentence completion
      test, and then all of them performed a self-referent judgment task with the
      adjectives. Immediately afterward, they were asked to recall as many adjectives
      as possible in an incidental memory task. Main results were as follows: The
      mildly depressed judged both positive and negative adjectives as equally
      applicable to themselves, while the controls judged negative ones to be less
      applicable. If self-focus was on the positive side of themselves, recall
      performance of the depressed became poorer, while that of the controls became
      better. If the focus was on the negative side, both groups recalled more positive
      adjectives, and fewer negative ones. These findings suggest that self-focused
      attention had different effects, depending on the person's depressive tendency.

PMID- 14584251
TI  - [Construction of the self-motivational strategies scale for junior high school
      students].
AB  - The two main purposes of the present study were to construct the self
      motivational strategies scale for junior high school students, and to examine the
      validity of the scale. In the first study, from the result of factor analysis on
      the data of 449 students, eight subscales were constructed, and differences in
      subscale scores between grades were found. In the second study, the relationships
      among eight self-motivational strategies, four types of motivation, academic
      stress coping strategies and appraisal of academic stressors were examined. It
      was shown that different aspects of students' self-motivational strategy were
      differentially related to their academic motivation and the use of some stress
      coping strategies. In addition, covariance structure analysis was carried out to
      investigate the validity of the scale. The results supported the construct
      validity of all but one of the subscales.

PMID- 14584252
TI  - [Stagewise estimation for regression analysis when independent variables are
      latent variables].
AB  - Psychological research often deals with psychological constructs that cannot be
      directly measured. Thus independent variables of regression analysis for an
      observable dependent variable are sometimes latent variables (factors) that are
      defined independently of the dependent variable. In this study we pointed out the
      problem associated with the use of factor analysis for the combined set of
      dependent variable and independent variables in such a cases; that is, the
      derived factors are different from those originally intended, and the true
      regression parameters cannot be reproduced. We proposed a stagewise estimation
      method to solve the problem. This method estimates parameters of measurement
      equation in the first stage, and then estimates parameters of structural equation
      in the second stage. Our proposed method enables calculation of standard errors
      of estimators using Bootstrapping method. Numerical studies showed that the
      proposed method improves the estimation efficiency over the conventional methods,
      and provides estimates which are robust with respect to misspecification of
      model.

PMID- 14584253
TI  - [Geometrical property of navigation].
AB  - There is a tendency that a blind or a blind-folded subject fails to return to a
      starting point within the range of errors when he or she walks to a place, next
      turns to right or left, and then comes back to the starting point. We studied
      this tendency from a non-Euclidean geometrical point of view. In Experiment 1,
      total of 28 blind-folded subjects walked to construct a square, a regular
      triangle and a circle. The result showed that the location of the final reaching
      point was on the fronto-right side of the starting point in the square and
      triangle conditions and went over the starting point in the circle condition. In
      Experiment 2, 15 subjects judged visual properties (angles and distances) of a
      triangle and constructed the triangle by walking. The walking loci were compared
      with the visual properties. It was found that the walking loci were curved,
      differing from the visual properties. These results implied that the walking loci
      agree with the nature of elliptic geometry.

PMID- 14584254
TI  - [Overassessment of losses with a delay].
AB  - The effects of delay in evaluating the future loss were examined. College
      students as participants were asked to indicate the amount of money they would
      pay immediately, supposing they had enough money to pay any amount, instead of
      paying the fixed amount (100,000 yen) in future after various delays. Two types
      of questions were employed. When the participants were asked to fill out the
      maximum amount they are willing to pay immediately rather than paying the fixed
      amount in future, the reported amount was described by a monotonically decreasing
      (hyperbolic or power) function of the delay. When they were asked the minimum
      amount for the alternative against which they would choose the fixed future
      payment, however, they answered greater amount than the fixed future amount. This
      result is in clear contrast to the generally reported "discount of value" for
      future reward. This kind of discrepancy between two types of questions was not
      observed when the participants made decisions between fixed and probabilistic
      alternatives, and the data fitted the theoretical functions adequately.

PMID- 14584255
TI  - [Recognition of sound pattern of words extracted from spoken sentences by
      preverbal infants].
AB  - The present experiment investigated the ability of recognition and long-term
      retention of sound pattern of words extracted from spoken sentences in preverbal
      infants. When preferences of 8-month-old Japanese infants for target words and
      for novel words were tested by head-turn preference procedure, immediately after
      being auditory exposed to spoken sentences that included the target words, they
      showed preference for target words significantly over novel words. They were able
      to recognize words that were presented within sentences previously. Moreover,
      such preference was confirmed when the infants were tested with a 2-week
      interval. On the other hand, their preference for prosodic properties of the
      exposed spoken sentences was not confirmed. Infants retain information of those
      words that were extracted from the speech analytically rather than holistically.

PMID- 14584256
TI  - [When "self-effacement" disappears: narratives of personal and group successes
      depending on an in group relationship].
AB  - The distinction between ingroup and outgroup has played an important role in
      group process research. However, much less attention has been paid to variations
      among ingroups. In this study, we attempted to demonstrate that different
      ingroups could have different psychological impacts on self and group serving or
      effacing behavior. In our social survey. Japanese respondents evaluated the
      importance and psychological meaning of two typical ingroups: their family and
      another social group in which they spent most of their time. They were also asked
      about their behavior in the presence of ingroup members from each group. Results
      indicated that people showed a self-effacing tendency in the social group,
      whereas they showed a self-serving tendency in their family. At the same time,
      they showed a group-serving tendency when they talked about the social group, but
      they showed the opposite, i.e., a group-effacing tendency, when they talked about
      their family. These differences are explained in terms of relationships with
      ingroup members.

PMID- 14584257
TI  - [Validity of attentional-style subscales for the Japanese version of the Test of
      Attentional and Interpersonal Style (TAIS)].
AB  - The six attentional-style subscales of the Test of Attentional and Interpersonal
      Style (TAIS, Nideffer, 1976) have been used mainly in the sport psychology area
      to investigate the relationship between attentional abilities and performance.
      This study assessed the validity of the Japanese version of the TAIS attentional
      style subscales with 157 male and 163 female students. A confirmatory factor
      analysis failed to validate Nideffer's attentional dimension of bandwidth (narrow
      to broad attention) and direction (internal to external). The findings replicate
      previous studies which showed that the structure of the TAIS attention-related
      subscales is not reasonable and its factorial validity does not meet the needs of
      psychometrics.

PMID- 14584258
TI  - [The construction, reliability and validity of a Japanese Need for Closure
      Scale].
AB  - The purpose of this study was to develop a Japanese Need for Closure Scale. In
      Study 1, Webster and Kruglanski's (1994) Need for Closure Scale was translated
      into Japanese, and administered to 240 undergraduates. Factor analysis of the
      Japanese version indicated that a three-factor structure was most appropriate. In
      Study 2, a revised scale was developed based on the result of Study 1, and
      administered to 577 undergraduates. Analysis of the revised Japanese Need for
      Closure Scale showed that it had sufficient internal consistency and test-retest
      reliability. In addition, confirmatory factor analysis indicated that the scale
      had a multidimensional structure. In Study 3, the scale was administered together
      with five relevant personality scales to 340 undergraduates, and sufficient
      construct validity of the scale was demonstrated.

PMID- 14584259
TI  - [Reliability and validity of Subjective Well-Being Scale].
AB  - In this study, a subjective well-being scale was developed, and its reliability
      and validity evaluated. The Subjective Well-Being Scale (SWBS) had twelve items
      which covered four domains. It was administered to 1005 adults and 520 college
      students. Results indicated that for the students, college life satisfaction and
      self-esteem had positive correlations with SWBS score. For the adults, marital
      satisfaction, workplace satisfaction, and household income satisfaction had
      positive correlations with the score. These findings showed considerable
      constructive validity for SWBS. In addition, internal consistency was
      sufficiently high, indicating the measure's high reliability. SWBS may be a
      simple but reliable and valid measure, and it is useful for examining subjective
      well-being of both adults and college students.

PMID- 14584260
TI  - EMTALA reg eases overall burden, but on-call physician issues still unclear.
AB  - The government's final Emergency Medical Treatment and Labor Act (EMTALA) rule
      clarifies and simplifies many issues that have frustrated ED managers, but there
      still are significant areas of concern. The rule clearly defines what facilities
      are covered by EMTALA, essentially restricting it to only true emergency
      departments. ED staff are not expected to render aid beyond hospital property.
      Physicians and hospitals have more flexibility in devising specialist on-call
      schedules. EDs may encounter more difficulty finding specialists, and those with
      physicians on call may be flooded with transfers.

PMID- 14584261
TI  - Blackout creates influx of patients, generator woes.

PMID- 14584262
TI  - Support grows for more family access in ED.

PMID- 14584263
TI  - Flowcharts are basis for symptom-based tools.

PMID- 14584264
TI  - Women's Pavilion nurtures new mothers.

PMID- 14584265
TI  - Back down to earth.

PMID- 14584266
TI  - Energy crisis?

PMID- 14584267
TI  - Call to arms?

PMID- 14584268
TI  - Ambulatory advice. Handling the planning and design challenges of outpatient
      facilities.

PMID- 14584269
TI  - Coming to America. English as a second language program helps ES department stay
      staffed.

PMID- 14584270
TI  - [Doctor-initiated clinical trials and the revised pharmaceutical affairs law].
AB  - In Japan, clinical trials aiming at application for approval of new drugs take a
      long time and a lot of money, and their quality thought to be poor. Japanese
      pharmaceutical companies tend to conduct more clinical studies in the United
      States and/or Europe than in Japan. The Ministry of Health, Labour and Welfare
      (MHLW) announced a three-year plan to facilitate clinical trials in Japan; the
      establishment of a large-scale clinical trial network, the improvement of the
      clinical research infrastructure, and the utilization of doctor-initiated
      clinical trials. The revised Pharmaceutical Affairs Law enables doctors and
      medical institutions to perform clinical trials using unapproved products
      spontaneously without any corporate sponsorship. Drugs needed by some patients
      but unapproved because they are unprofitable for companies are expected to be
      approved under this system. MHLW stipulated the ethical and scientific quality
      standard of doctor-initiated clinical trials, which is consistent with the
      principles of the Declaration of Helsinki, and Good Clinical Practice (GCP). To
      establish a system that allows expedited approval of safer and more effective
      products, the integration of the functions of the current review bodies, such as
      the Organization for Pharmaceutical Safety and Research (OPSR) and the
      Pharmaceuticals and Medical Devices Evaluation Center (PMDEC), into an
      independent administrative agency is scheduled.

PMID- 14584271
TI  - [Cancer chemotherapy; past, present and future--from the aspect of fundamental
      studies].
AB  - Advances in cancer chemotherapy has been supported greatly by the progresses of
      the studies of tumor cell biology, development of new anticancer drugs, fundament
      studies related to drug resistance, biochemical modulation and others. In this
      paper, biological studies influenced on cancer chemotherapy in early days such as
      skipper's law, Goldie-Coldman hypothesis and others, development of various
      anticancer drugs (which were discovered in Japan or abroad), studies of drug
      resistance, biochemical modulation were briefly reviewed. Also in the near
      future, some novel molecular-targeted drugs will serve as the useful anticancer
      drugs.

PMID- 14584272
TI  - [Chemotherapy cancer treatment during the past sixty years].
AB  - Although history of cancer chemotherapy is relatively short, its role is
      expanding. Cancer chemotherapy provides variably effective treatment for the
      majority of human cancer and curative treatment for some categories of cancer.
      The role of chemotherapy will expand further and play an even greater role in
      improving both the survival and quality of life for patients with cancer. This
      progress has resulted from many scientific efforts, including drug development,
      pharmacology, preclinical experiment, quantitative criteria for response and
      series of clinical trials in which the importance of dose schedule, of sequencing
      chemotherapeutic agents, and particularly of combination chemotherapy was
      studied. While these progress has been substantial, we still have a long way to
      go. The current studies in basic tumor biology, clinical innovations, and the
      interaction between host and tumor provide real progress in the treatment of
      cancer.

PMID- 14584273
TI  - [Hematologic tumors].
AB  - Development of cytarabine and daunorubicin has made a cure for acute myeloid
      leukemia (AML) possible. Current first line chemotherapy is a combination of
      idarubicin plus cytarabine. Acute promyelocytic leukemia has the highest cure
      rate among AML due to the introduction of ATRA. Current first line chemotherapy
      for advanced Hodgkin's lymphoma is ABVD, based upon results of a prospective
      randomized study comparing MOPP, ABVD and MOPP/ABVD. CHOP has been frequently
      selected as first line chemotherapy for advanced non-Hodgkin's lymphoma, based
      upon results obtained in a phase III study that compared CHOP versus second and
      third generation combinations.

PMID- 14584274
TI  - [The platelet-sparing effect of carboplatin and docetaxel combination
      chemotherapy for lung cancer].
AB  - Paclitaxel and carboplatin chemotherapy is reported to be a platelet-sparing drug
      combination. The objective of this study was to elucidate whether docetaxel with
      carboplatin has a similar platelet-sparing effect. This study investigated the
      time-course of the changes in the platelet count and the circulating
      concentration of thrombopoietin (TPO), a platelet growth factor, during
      combination chemotherapy consisting of carboplatin and docetaxel. Eleven patients
      with advanced lung cancer were enrolled; 8 receiving carboplatin and docetaxel
      (docetaxel group), and 3 receiving carboplatin and irinotecan (irinotecan group).
      The time-course profiles of the platelet count and the circulating TPO
      concentration were determined and compared between the two groups. The platelet
      count decreased significantly only in the irinotecan group, and on day 15 after
      therapy the thrombocytopenia was pronounced in comparison with that in the
      docetaxel group. The circulating TPO concentration remained almost constant in
      the irinotecan group, with no significant increases, while that in the docetaxel
      group was increased significantly on day 4 (p < 0.05), day 8 (p < 0.05), and day
      15 (p < 0.01) after therapy. There was also a significant difference between the
      docetaxel group and irinotecan group with respect to circulating TPO
      concentration (p < 0.05). These results suggest that docetaxel might also have a
      platelet-sparing effect on the anti-platelet activity of carboplatin, mediated by
      levels of circulating TPO concentration.

PMID- 14584275
TI  - [Retrospective study on utility of irinotecan hydrochloride in patients with
      advanced and recurrent breast cancer].
AB  - Irinotecan hydrochloride has been administered to patients with breast cancer
      resistant to anthracyclines and/or taxanes in our department. A retrospective
      analysis of the efficacy and toxicity of irinotecan therapy was conducted to
      clarify its clinical usefulness. A total of 35 consecutive patients with advanced
      or recurrent breast cancer were treated with irinotecan between June 1996 and
      March 2002. The patients ranged in age from 37 to 66 years old (median, 52). The
      most frequent metastatic lesion was in the liver. The number of previous
      chemotherapy was 2 to 7 regimens (median, 3). Ninety-one percent and 97% of the
      tumors were anthracycline- and taxane-resistant, respectively. The weekly dose of
      irinotecan was 40-160 mg/body (median, 100), and the total dose was 40-6, 110
      mg/body (median, 840). An objective response rate of 6% and a clinical benefit
      rate of 23% were obtained. The median time-to-progression and overall survival
      were 3 months and 8 months, respectively. Severe toxicity (grade 3 or 4) was
      observed in 34% of the patients for a decrease in the white blood count, in 26%
      for neutropenia, in 17% for nausea/vomiting and in 6% for diarrhea. Although this
      study suggests that irinotecan is a clinically useful treatment of anthracycline-
      and/or taxane-resistant breast cancer, its anti-tumor effect was not
      satisfactory. The activity of first-line irinotecan therapy or the combined use
      of irinotecan with other agents should be investigated in clinical studies.

PMID- 14584276
TI  - [Harvesting of autologous peripheral blood stem cells following percutaneous
      isolated hepatic perfusion for patients with advanced hepatocellular carcinoma].
AB  - Percutaneous isolated hepatic perfusion (PIHP) using high-dose chemotherapeutic
      agents is highly effective for advanced hepatocellular carcinoma in comparison
      with conventional regional and systemic chemotherapies. However, bone marrow
      toxicities resulting from the first PIHP preclude additional second/third PIHP in
      some cases. In an attempt to increase safety of repeated PIHP, autologous
      peripheral blood stem cells (PBSC) were harvested after the first PIHP in nine
      patients with multiple hepatocellular carcinoma with administration of G-CSF.
      PBSCs were successfully harvested in only three patients with relatively well
      preserved liver function, whereas PBSC harvests were unsatisfactory in the
      remaining six patients with highly impaired liver function. The possible reasons
      for this phenomenon may include hypofunction of bone marrow in cirrhotic
      patients, and an insufficient use of G-CSF in the present study. Alfa-fetoprotein
      mRNA, determined by nested RT-PCR, was detected in six PBSCs, indicating frequent
      contamination of tumor cells. More precise studies are needed before clinical
      application of autologous stem cell infusion for patients with malignant hepatic
      tumors and impaired liver function.

PMID- 14584277
TI  - [Clinical evaluation, including QOL of TS-1 for patients with locally advanced or
      recurrent gastric cancer at ambulatory setting].
AB  - PURPOSE: Forty-nine patients with locally advanced or recurrent gastric carcinoma
      were treated with a novel 5-FU derivatives, TS-1, in an ambulatory setting. The
      response rate and adverse effect as well as patients' QOL were evaluated.
      RESULTS: The overall response rate was 38.8% (19/49). Partial response (PR) was
      obtained in 3 (27%) of 11 primary lesions of the stomach, in 10 (48%) of 21 lymph
      node metastases, in 6 (40%) of 15 liver metastasis, and in 4 (33%) of 12
      peritoneal disseminations, respectively. The average response period was 222.2
      days and the 50% survival period was 382 days. In addition, patients' QOL,
      evaluated by questionnaire, was maintained relatively well during treatment.
      Conversely, the adverse effects (greater than grade 3) were bone marrow
      suppression in 3 cases and toxic dermatitis in 1 case, respectively. CONCLUSION:
      Taken together it is reasonable to conclude that TS-1 is safe and effective for
      patients with locally advanced or recurrent gastric carcinoma in an ambulatory
      setting, and is promising as a first line treatment in the general hospital.

PMID- 14584278
TI  - [Evaluation of hepatic arterial infusion chemotherapy with low-dose leucovorin
      and 5-FU from reservoir for multiple liver metastases by colorectal cancer].
AB  - 5 patients with colorectal cancer with multiple liver metastases underwent
      resection of primary lesions. We then evaluated the effects of hepatic arterial
      infusion chemotherapy with low-dose leucovorin and 5-FU. Weekly, dl-leucovorin of
      30 mg/body or l-leucovorin of 25 mg/body was administered as a bolus, then 5-FU
      of 500 mg/body was administered for 1 hour through the hepatic artery from the
      subcutaneous reservoir on an outpatient basis. 2 of 5 patients achieved a CR of
      liver metastases, but later 1 of these 2 cases had metastases of bone and lung.
      No adverse effects, such as nausea, vomiting, diarrhea or bone marrow
      suppression, were seen after this treatment in any of the patients.

PMID- 14584279
TI  - [Evaluation of QOL with orally disintegrating antiemetic tablets in outpatient
      chemotherapy].
AB  - An investigation into the effect of orally disintegrating antiemetic tablets
      (ramosetron OD 0.1 mg) on 16 outpatients undergoing chemotherapy for recurrent
      gynecologic malignancies was carried out using a questionnaire to evaluate their
      quality of life (QOL). The patients were divided into 2 groups: a control group
      in which the patients received only an intravenous drip infusion of 0.3 mg of
      ramosetron on the day of their chemotherapy and a double antiemetic therapy group
      in which the patients were treated with orally disintegrating antiemetic tablets
      for 4 days in addition to the intravenous drip. When outpatient chemotherapy
      (paclitaxel 80 mg/m2/1 h div + CBDCA AUC 2/1 h div) was performed, a comparison
      was made between the 2 groups, based on the results of a QOL questionnaire for
      antiemetic therapy during cancer chemotherapy (Ishihara's QOL survey method).
      This study found a greater improvement in QOL in the double antiemetic therapy
      group on days 2 to 4, a period when deterioration in QOL is usually observed.
      These findings suggest that orally disintegrating antiemetic tablets as a measure
      to reduce delayed nausea and vomiting are useful for improving QOL.

PMID- 14584280
TI  - [Two head and neck cancer patients who responded to chemotherapy consisting of
      only TS-1].
AB  - We report two head and neck cancer patients who responded to TS-1. Case 1, a 52
      year-old man was admitted to our department a diagnosis of supraglottic laryngeal
      cancer (T3N2cM0) on January 25, 2000. Concurrent chemoradiotherapy consisting of
      2 courses of chemotherapy and radiation therapy at 70.2 Gy was administered.
      After the treatment, a biopsy showed a remaining cancer in the primary lesion.
      Since the patient refused to undergo surgery, the patient was followed up at the
      outpatient clinic using UFT at 400 mg/day. Because pulmonary metastasis was
      detected by chest CT, administration of TS-1 was started. TS-1 was administered
      at the conventional dose of 120 mg/day for 4 weeks followed by a 2-week rest.
      According to a CT conducted after 2 courses, the mass in the lung field
      disappeared and the clinical outcome was judged to be a CR. The TS-1
      administration is still continuing, and the patient's condition also remains a
      CR. Case 2 was a patient with highly-differentiated adenocarcinoma in the ethmoid
      sinus (T3N2bM0). The patient was inoperable and was given radiation therapy of
      64.8 Gy. Because of no change of the tumor after radiotherapy, TS-1 was
      administered at 60 mg x 2/day for 4 weeks followed by a 2-week rest. After TS-1
      was administered for 3 courses, a CT showed a remarkable regression of the tumor
      resulting in a PR for the primary and the neck lesion. Upper gastrointestinal
      endoscopy during the 4th course detected a gastric ulcer of the A1 stage, and the
      patient was immediately admitted to the hospital. The ulcer was an adverse
      reaction of grade 3, which was improved by conservative therapy. TS-1 was
      restarted with a dose of 100 mg/day on April 11. No particular adverse reaction
      has been observed since then. The patient has received 13 courses of TS-1 and is
      still receiving TS-1. No clear tumor has been observed, and the clinical outcome
      is considered to be a CR. TS-1 is considered to be an excellent oral anticancer
      drug in terms of its anti-tumor effect and the patient's QOL.

PMID- 14584281
TI  - [Two cases of recurrent breast cancer successfully treated with paclitaxel weekly
      therapy].
AB  - The patients were a 57-year-old and a 38-year-old woman who had supraclavicular
      lymph node and multiple lung metastases from breast cancer. They were given 3 and
      4 courses of paclitaxel (TXL) weekly therapy (80 mg/m2, day 1, 8, 15, repeated
      every 4 weeks). One patient had received docetaxel (TXT) and CEF therapy
      previously. There were no severe adverse effects except leukopenia, neutropenia
      and alopecia. The weekly TXL therapy brought complete remission against the
      supraclavicular lymph node and multiple lung metastases. The durations of the
      response to this weekly therapy were 15 and 5 months, respectively, and their
      effects have continued to the present. We believe that the weekly TXL therapy is
      a well-tolerated, feasible and safe administration schedule on an outpatient
      basis, and improves the patient's quality of life. Furthermore, we suggest the
      possibility of TXL being effective against both TXT and anthracycline-resistant
      breast cancer.

PMID- 14584282
TI  - [A case of advanced gastric cancer responding to neoadjuvant TS-1/CDDP therapy].
AB  - A 62-year-old advanced gastric cancer patient with bulky N2 lymph node metastases
      was treated by neoadjuvant chemotherapy with TS-1 and CDDP. TS-1 (100
      mg/body/day) was orally administered for 3 weeks followed by a drug-free 2-week
      period as 1 course, and 75 mg/body/day of CDDP was administered by intravenous
      drip on day 8. After the first course, the primary lesion and the regional lymph
      node metastases showed partial response in terms of size. No serious drug adverse
      reaction was observed. During the second course, urgent total gastrectomy with
      distal pancreatectomy and splenectomy was performed for massive bleeding from a
      deep gastric peptic ulcer. The histopathological findings showed complete
      response of the carcinoma as primary lesion except for two sites of minimal
      lymphatic permeation and one lymph node (No. 8a) metastasis. The combined use of
      TS-1 and CDDP is useful as neoadjuvant chemotherapy for advanced gastric cancer.

PMID- 14584283
TI  - [A case of advanced gastric cancer with multiple liver metastases responding to
      TS-1 and CDDP].
AB  - A 44-year-old male presented to our hospital with abdominal pain. The upper
      endoscopy revealed advanced gastric cancer. On the abdominal CT, there was
      evidence of multiple, massive liver metastases. After total gastrectomy, the
      patient was treated with daily oral administration of 120 mg TS-1 for 4 weeks
      followed by 2 weeks' rest and 6 weekly infusions of 10 mg CDDP in an intra
      hepatic artery as 1 cycle. On the follow-up CT, the liver metastases had
      decreased significantly both in size and number after 2 cycles. The current case
      suggests that TS-1 and CDDP may have a potent therapeutic efficacy in cases of
      advanced gastric cancer with multiple liver metastases.

PMID- 14584284
TI  - [Complete response of primary tumor in a case of advanced gastric cancer with
      liver metastasis treated by TS-1 plus divided administration of CDDP].
AB  - A 62-year-old female patient was hospitalized for general fatigue and appetite
      loss. Type 3 gastric cancer (moderate differentiated adenocarcinoma) with liver
      metastasis (S8) and direct invasion to the retro-peritoneal space and duodenal
      third portion was detected by endoscopic and radiographic examination. This case
      was judged to be unresectable from these findings. TS-1 plus divided
      administration of CDDP was performed. TS-1 (100 mg/day) was administrated from
      day 1 to 21 followed by 14 days rest as one course. CDDP (20 mg/m2) was infused
      for 2 hours on day 1, 8, and 15. One course was done in the hospital, and the
      following 2 courses as ambulatory treatment. Grade 2 neutropenia was observed as
      an adverse reaction. At the completion of 3 courses, partial response in the
      primary tumor, complete response in the duodenal third portion and no change in
      the liver metastasis were assessed by examination. Because of this remarkable
      down-staging, distal gastrectomy and radiofrequency ablation (RFA) for liver
      metastasis were performed. There was no evidence of direct invasion to the other
      organs from the primary tumor in intraoperative findings. Pathological
      examination revealed the disappearance of carcinoma cell in the resected stomach
      and the surrounding lymphnodes. In conclusion, this chemotherapy regimen has an
      excellent antitumor effect with low toxicities. Therefore, this regimen was
      comparatively safe for outpatients and was an effective neo-adjuvant
      chemotherapy.

PMID- 14584285
TI  - [Efficacy of TS-1 in patients with peritonitis carcinomatosa from gastric
      cancer].
AB  - Medical treatment with TS-1 was performed in patients with gastric cancer with
      peritonitis carcinomatosa. The median survival time for the patients who
      underwent distal or total gastrectomy was 14.0 months, and that for the patients
      who underwent exploratory laparotomy was 9.3 months. Compared with other medical
      care, the anti-cancer drug TS-1 enabled prolonged survival time and shortened
      hospitalization. Since TS-1 had few side effects, it was useful to patients
      suffering from gastric cancer with peritonitis carcinomatosa.

PMID- 14584286
TI  - [A case of distant metastasis from advanced gastric cancer treated with TS-1,
      which maintained NC (no change) for 9 months].
AB  - A 57-year-old woman was admitted to our hospital for advanced gastric cancer
      located in the gastric antrum. Abdominal CT scan revealed multiple liver
      metastases and lymph node metastasis along the abdominal aorta which was
      diagnosed as stage IV gastric cancer. The patient received daily oral
      administration of 75 mg TS-1, a novel oral anticancer agent. Each treatment
      course consisted of a four-week administration followed by two drug-free weeks.
      No change (NC) was observed in the liver metastasis on the abdominal CT scan
      after TS-1 administration, but lymph node swelling along the abdominal aorta
      decreased (PR). Grade 2 depilation was observed as the only adverse effect. The
      patient had a performance status of 1 or 2, and kept a fair QOL. TS-1 is an
      excellent new anticancer agent and, we have high expectations for its use in
      combined therapy with other drugs.

PMID- 14584287
TI  - [A case of multiple liver metastases of colon cancer with PyNPase-positive
      successfully treated with 5'-DFUR].
AB  - A 75-year-old man was diagnosed with transverse colon cancer. We therefore
      performed a transverse colectomy. Diagnosis of multiple liver metastases was made
      by intraoperative palpation, core needle biopsy and postoperative abdominal CT
      scan. 5'-deoxy-5-fluorouridine (5'-DFUR) 800 mg/day was administered orally after
      the surgery. After 2 months of administration, an abdominal CT scan showed the
      metastatic lesions of liver were reduced. After 8 months, an abdominal CT scan
      showed no evidence of liver metastases. Pyrimidine nucleoside phosphorylase
      (PyNPase), an enzyme that converts 5'-DFUR to 5-FU, has an important role in the
      expression of the anti-tumor activity of 5'-DFUR. Primary specimens of this case
      were regarded as PyNPase-positive. We think that administration of 5'-DFUR may be
      a useful treatment for advanced colon cancer that is PyNPase-positive.

PMID- 14584288
TI  - [A case of liver metastasis from gallbladder cancer with marked response to
      arterial infusion chemotherapy].
AB  - The patient was a 68-year-old woman who visited a nearby clinic with a chief
      complaint of right hypochondrial pain. A mass lesion in the gallbladder was found
      by ultrasonography. She was referred to our hospital for further examination and
      was diagnosed with gallbladder cancer. Cholecystectomy and bile duct resection
      were performed. Six months after the surgery, multiple liver metastases were
      found. A subcutaneous implant reservoir was placed in the hepatic artery from the
      right femoral artery. After arterial infusion chemotherapy by 5-FU and CDDP, or 5
      FU alone, liver metastasis markedly responded and became undetectable, and
      therapy was therefore discontinued. The patient has been disease-free without any
      sign of recurrence for 7 months after CR was achieved. It is suggested that
      arterial infusion chemotherapy is useful and safe for the treatment of liver
      metastasis from gallbladder cancer.

PMID- 14584289
TI  - [A case of renal cell carcinoma with lymph node metastasis keeping remission for
      five years by adjuvant immunotherapy with ubenimex].
AB  - We report herein the long-term remission of a woman following postoperative
      ubenimex therapy. A 46-year-old woman with a tumor in the left kidney and a
      swollen para-aortic lymph node was referred to our department for surgery.
      Preoperative computed tomography revealed a stage IV renal cell carcinoma. Since
      her right kidney naturally ruptured after hospitalization, the patient underwent
      bilateral kidney and partial paraaortic lymph node dissection. Histopathological
      tests revealed that the tumor was T3, N2, M0, mixed type. As the residual lymph
      node was swollen at 4 months after the operation, treatment with ubenimex was
      started. Five years after the operation, no new lymph node metastases were
      recognized under continuous treatment with ubenimex. Single administration of
      ubenimex appears to be effective for cases of renal cell carcinoma with lymph
      node metastasis to maintain good patient QOL because of its few side effects.

PMID- 14584290
TI  - [Simultaneous detection of both non-Hodgkin's lymphoma cells and breast cancer
      cells in pleural effusion--a case report].
AB  - A 55-year-old woman underwent breast-conserving surgery with irradiation for
      Stage IIB (T2 N1 M0) breast cancer of her right breast. Thereafter, she was
      treated orally with oral UFT and tamoxifen. Three years following surgery, she
      was diagnosed as having a non-Hodgkin's lymphoma. She underwent 6 cycles of EPOCH
      G (etoposide, vincristine, adriamycin, cyclophosphamide, prednisolone, G-CSF)
      therapy, and obtained complete remission. Two years later, her neck and inguinal
      lymph nodes were swollen. Biopsy confirmed the relapse of NHL. She underwent
      salvage chemotherapies of MST-16, carboplatin, IVAC, and CPT-11, but the disease
      was refractory. In May 2000, bilateral pleural effusion was detected.
      Cytomorphologically, the pleural fluid specimen showed both atypical lymphoid
      cells and adenocarcinoma cells simultaneously. Existence of double cancer in the
      pleural effusion has not been reported, suggesting that this case is rare.

PMID- 14584291
TI  - [A case of advanced gastric cancer treated with weekly paclitaxel with
      measurement of paclitaxel concentrations in blood and ascites].
AB  - We measured paclitaxel (PTX) concentrations in blood and ascites in a patient
      with advanced gastric cancer treated with weekly paclitaxel (80 mg/m2). After 180
      minutes from infusion of PTX, the concentration of PTX in ascites was 13 ng/ml,
      which was more than the reported cytotoxic dose of PTX (8.5 ng/ml). The
      concentration of PTX in ascites was retained, and rose rather slowly during a 24
      hour period. The patient died soon after the measurement, meaning this
      measurement was taken at a time when the antitumor effect was ineffective and
      under poor general conditions. The result suggested, however, that the desired
      concentration of PTX in ascites can be obtained with a smaller dose of PTX in a
      regimen of weekly PTX.

PMID- 14584292
TI  - The 2nd conference on Asian trends in prostate cancer hormone therapy.
AB  - Among the aims of the 2nd Conference on Asian Trends in Prostate Cancer Hormone
      Therapy, Hong Kong, December 7-8, 2002, was to lay the groundwork for eventually
      having cooperative or collaborative studies of prostate cancer specifically in
      Asian patients. The conference was divided into 2 sessions. In the first session,
      entitled "Current Status of Therapy for Prostate Cancer in Asian Countries," the
      results of analysis of 100 patients with prostate cancer enrolled in the Patients
      Registration System is each of the 6 participating Asian countries were
      discussed. The Patients Registration System is a database template established by
      the Japanese Urological Association that allows physicians to compare prostate
      cancer therapy in the different Asian countries. Session 2 was devoted to a
      "Roundtable Discussion on the Establishment of Asian Guidelines for Prostate
      Cancer." This session included 2 lively discussions, on whether Asian physicians
      can apply Western clinical data to Asian patients, and the need for Asian
      clinical data and developing clinical trials in the region, respectively.

PMID- 14584293
TI  - [Successful pregnancy in a hemodialysis patient].

PMID- 14584294
TI  - [Hemodialysis in pregnancy].
AB  - Pregnancy brought to term is rare in patients undergoing haemodialysis. Both
      mother and foetus are exposed to lethal from complications frequently caused by
      hypertension and anaemia. We are reporting the first case of pregnancy observed
      in an haemodialysis centre in Antananarivo, Madagascar. In spite of the modest
      means of the centre (use of acetate, lack of recombinant erythropoietin, limited
      biological controls) the foetus could be kept by intensification of the dialysis.
      No complication occurred to the mother when in the literature its frequency is
      16%. The baby was premature and low weighted. His mental and physical development
      was normal. This success is the consequence of heavy management especially for
      the patient.

PMID- 14584295
TI  - [Drug induced linear IgA bullous dermatosis].
AB  - Linear IgA disease is an autoimmune subepidermal bullous disease in which linear
      IgA deposits are found at the basement membrane zone. It is classically
      idiopathic but a drug-induced variant seems to be individualized in which
      cutaneous lesions resolve spontaneously after cessation of responsible treatment.
      Among the commonly implicated drugs, vancomycin is the most frequently reported.
      One should not however ignore other precipitating events sometimes associated,
      particularly infectious diseases and non-lymphoid or lymphoproliferative
      malignancies. Authors present here clinical and histological features of this
      disease as well as drugs that have been implicated.

PMID- 14584296
TI  - [Review of quality of life instruments used in end-stage renal disease].
AB  - Health related quality of life (HRQOL) indicators take into account the personal
      perception of health, and are proposed as an alternative for efficacy indicators
      in medical and therapeutic decision making. They provide, due to elaboration and
      validation of a questionnaire, a standardised assessment of the health status
      perception. This paper provides a review of a variety of HRQOL instruments
      developed for patients suffering end-stage renal disease (ESRD). Generic
      instruments are designed to be applicable in general population and disease
      targeted instrument are potentially more sensitive to the characteristics of a
      specific population. Among HRQOL instruments, we found 4 generic questionnaires
      (the Sickness Impact Profile, the SF 36, the Nottingham Health Profile and the EQ
      5D), 3 disease-targeted questionnaires developed for ESRD patient undergoing
      dialysis (the Kidney Disease Quality of Life instrument, the Kidney Disease
      Questionnaire and the Choice Health Experience Questionnaire), 1 questionnaire
      specific for ESRD patients (the HRQOL questionnaire), and 2 specific disease
      targeted instruments for renal transplant (the Kidney Transplant Questionnaire
      and the ESRD Symptom Checklist-Transplantation Module). In France, very few
      studies on the quality of life of ESRD patients were published; no specific
      questionnaire validated in French is yet published.

PMID- 14584297
TI  - [Randomized trials in the prevention of recurrent calcium oxalate stones].
AB  - Kidney stone, with or without lumbar pain, is a major health care problem because
      of its prevalence and cost for both the patient and the society. Although,
      surgical procedures are well known, medical treatment and recurrences prophylaxis
      are uncodified. Fifteen stone recurrence prevention studies have been reviewed,
      evaluating dietary intake and drugs. The most important factor is a daily
      diuresis of at least 2 liters. Calcium intake shouldn't be restricted, whereas
      oxalate, sodium, and protein intakes have to be limited. Hyper and
      normocalciuretic kidney stone formers improve their outcome with thiazide or
      indapamide treatment. Hyperuricosuria justifies allopurinol. Potassium citrate
      (without sodium) may decrease recurrence risk, even in patients without
      hypocitraturia.

PMID- 14584298
TI  - [Parvovirus B19 infection after renal transplantation].
AB  - Despite improvements in the management of transplanted patients, viral infections
      following transplantation remain significant causes of morbidity and mortality.
      New laboratory techniques have improved the diagnosis of pathogenic viral
      infections following transplantation such as parvovirus B19 infections. Anemia is
      the principal abnormality associated with parvovirus B19 infection but other
      complications have been reported such as hepatitis, glomerulonephritis,
      myocarditis or arthritis. In immunocompromised patients, infection, which may
      remain undiagnosed by serological tests is usually assessed by PCR. Patients may
      spontaneously recover. However, in the absence of specific antiviral therapy,
      intravenous immunoglobulin appears to be the more efficacious treatment.

PMID- 14584299
TI  - [The NEPHRODIAB2 randomized trial].

PMID- 14584300
TI  - Why focus on 'fear of childbirth'?

PMID- 14584301
TI  - Knowledge, attitude, and behavior of female students concerning contraception in
      Athens, Greece.
AB  - The aims of this study were to investigate the knowledge, attitudes and behavior
      of female high school and university students concerning contraception. The study
      was performed at the Alexandra University Hospital in Athens. A total of 297
      female students participated in the study. A questionnaire was used to evaluate
      the depth of knowledge and attitude of respondents concerning contraception. Our
      findings suggest students have a defective knowledge of contraception. Their main
      source of information were friends but the majority would prefer to receive
      information from doctors. The most popular contraceptive method was the male
      condom. The attitude and behavior of young women in our study were consequently
      defective. In conclusion, there is a need to provide students with correct,
      detailed and broad-based information on conception and contraception as part of
      the school curriculum to help them acquire adequate knowledge and develop
      appropriate attitudes on contraception and sexual health.

PMID- 14584302
TI  - Patterns of emotional responses to pregnancy, experience of pregnancy and
      attitudes to parenthood among IVF couples: a longitudinal study.
AB  - The aim of this longitudinal study was to compare couples who had conceived by in
      vitro fertilization (IVF) with couples who had conceived naturally, regarding
      patterns of emotional response to different stages of pregnancy and to compare
      their expectations of and attitudes to pregnancy, parenthood and children. Fifty
      seven IVF women and 55 of their male partners, and a control group of 43 pregnant
      women and 39 of their male partners participated. They completed scales measuring
      emotional responses to pregnancy, attitudes to pregnancy, parenthood and
      children. The IVF couples were interviewed about their experience of pregnancy.
      The overall anxiety about losing the pregnancy was higher among the IVF couples
      from early to late pregnancy. The IVF women experienced the pregnancy in a more
      positive way and they were less concerned about the child's gender and loss of
      freedom in their future lives as parents compared to controls. The IVF men were
      more anxious about the baby being injured during birth. The interviews with the
      IVF couples confirmed the self-ratings. In conclusion, the results suggest that
      it is important for healthcare providers to pay attention to an elevated anxiety
      among IVF couples and to give them extra time to discuss emotions during
      pregnancy and their future life as parents.

PMID- 14584303
TI  - Factor structure of the modified Moos Menstrual Distress Questionnaire:
      assessment of prospectively reported follicular, menstrual and premenstrual
      symptomatology.
AB  - Despite the wide usage of the Moos Menstrual Distress Questionnaire (MDQ) in
      menstrual cycle research, the factor structure of the questionnaire has received
      relatively little attention since derived by Moos in 1968. This issue is one of
      considerable importance given that the methods of data collection used by Moos
      have since been subject to serious criticism. The aim of the current study was to
      determine whether Moos' factors could be replicated based on daily and
      prospective completion of the MDQ in women who were unaware of the study aims.
      One hundred and eighty-seven women from the general community (mean age 30 years)
      completed a modified version of the MDQ daily for 70 days. Principal components
      analysis of the modified MDQ items during the follicular, late luteal and
      menstrual phases indicated that a six-factor solution similar to that derived by
      Moos best summarized the data. A number of symptoms, however, loaded highly on
      more than one factor. This created some instability in the solution and may
      explain the discrepancies in previous research. Nonetheless, it was concluded
      that the Moos factors effectively represent the structure of menstrual cycle
      symptoms.

PMID- 14584304
TI  - The association of gynecological symptoms with psychological distress in women of
      reproductive age: a survey from gynecology clinics in Beirut, Lebanon.
AB  - To date there has been no previous research into a possible association between
      psychological distress and gynecologic symptoms in the Arab world. We
      hypothesized that psychological distress would be associated with specific
      gynecologic complaints as well as with psychosocial factors. We conducted a cross
      sectional study of women attending gynecology clinics in Beirut, Lebanon. The
      study sample consisted of 355 women aged 18 to 49 years who were seeking
      healthcare from gynecologists affiliated with two general teaching hospitals in
      Beirut. Psychological distress was assessed using the General Health
      Questionnaire (GHQ). Gynecologic complaints were assessed by asking women about
      presenting gynecologic symptoms. Women who visited the gynecologists for specific
      complaints, for post-surgical follow-up, or for insertion of coils or other
      services were more likely to be distressed than women who were attending for a
      general checkup (chi 2 = 9.466, p = 0.024). About 50% of women who reported
      abdominal pain or breast pain also reported significant psychological distress.
      Only bleeding and infertility were not significantly associated with
      psychological distress. It is concluded that a high proportion of women who
      attend gynecology clinics with specific complaints report psychological distress.
      Our findings highlight the importance of considering the psychological component
      of gynecological morbidity.

PMID- 14584305
TI  - Oral contraception and cyclic changes in premenstrual and menstrual experiences.
AB  - Despite the widespread use of oral contraceptives (OC) there is no consensus
      regarding their effect on menstrual cycle experiences. This study examines the
      cyclic changes of prospectively collected, daily menstrual cycle experiences of
      two groups of 'healthy women' using monophasic and triphasic OC compared with a
      group using non-hormonal contraception. A total of 119 'healthy women' using
      monophasic, triphasic or non-hormonal contraception for three months, made daily
      ratings over at least two complete menstrual cycles. Cyclic changes of ratings
      within and between the groups were analyzed. The three groups showed significant
      cyclic changes in abdominal fullness, abdominal discomfort, breast fullness,
      general 'premenstrual syndrome-like symptoms' and in at least two mood ratings.
      Maximal changes in ratings occurred during the late premenstrual and menstrual
      phases. There were no significant differences between the three groups in cyclic
      changes for any physical rating, but there were for tiredness or fatigue (non-OC
      users reported experiencing tiredness or fatigue more frequently than the OC
      users) and sadness or depression (non-OC users experienced sadness or depression
      less frequently than OC users during the early part of the cycle, followed by a
      sharp rise from early premenstrual to the menstrual phase). There were no
      significant cyclic differences in ratings between the monophasic and triphasic
      groups. In conclusion, 'healthy women' using OC experience premenstrual and
      menstrual changes. Any differences between OC formulations are subtle and not of
      clinical significance in 'healthy women' already established on monophasic or
      triphasic hormonal contraception.

PMID- 14584306
TI  - Psychological profiles among women with vulvar vestibulitis syndrome: a chart
      review.
AB  - The purpose of this study was to assess the prevalence and type of psychological
      distress in women with vulvar vestibulitis syndrome (VVS). A retrospective chart
      review was conducted of all women receiving a diagnosis of VVS referred to a
      tertiary care facility during a two-year period. Brief psychological
      questionnaires, including the Personality Assessment Screener, Fear of Negative
      Evaluation Scale, Golombok-Rust Inventory of Sexual Satisfaction, and the Phobia
      Rating Scale were administered. Fifty-consecutive cases were reviewed along with
      12-15 month follow-up data for 41 cases. Phobic anxiety to vaginal touch or entry
      was significantly higher in women with VVS than normative data. Fear of Negative
      Evaluation was a strong associated feature, and for 30% approached clinically
      significant levels. Twenty-six percent showed a moderate, while another 26%
      showed a mild clinically distressed profile. Negative affect and social
      withdrawal were among the most frequently endorsed variables. Improvement in
      allodynia and intercourse were both related to these psychological variables, and
      a multiple regression analysis supported the use of psychological instruments in
      addition to standard medical assessment. A subgroup of women with VVS display
      clinically significant broad based psychological distress that warrants
      additional assessment. The use of psychological questionnaires in addition to
      medical assessment of women with VVS may provide valuable information predictive
      of treatment needs and response.

PMID- 14584307
TI  - The terrible uncertainty of paternity.

PMID- 14584308
TI  - Road to recovery. Eight months after SARS hit, is Hong Kong finally back?

PMID- 14584309
TI  - The secret killer.

PMID- 14584310
TI  - Why do drug companies fear this man?

PMID- 14584311
TI  - Save an arm and a leg.

PMID- 14584312
TI  - The three revolutions in acetabular revision surgery for total hip replacement:
      1. Definite and 2. Probable.
AB  - Acetabular revision surgery has been and remains a difficult challenge in total
      hip replacement surgery. Cemented acetabular revisions have not worked out as
      well as would be desirable. With the introduction of the hemispherical cementless
      acetabular component, either pressfit or fixed with screws, a major change has
      been accomplished in the problem of fixation. This is the first revolution in
      acetabular revision surgery. The second and third revolutions are potential and
      important. The second revolution that may take place is the reduction in
      periprosthetic osteolysis, secondary to the use of highly crosslinked, melted,
      polyethylene. The third potential revolution is the reduction in the incidence of
      dislocation that could result from the use of heads of larger diameter. The in
      vitro studies suggest that certain highly crosslinked polyethylenes can be used
      with a larger head diameter without the risk of a major increase in particulate
      debris. Potentially this could address many of the issues of the high incidence
      of dislocation following acetabular revisions. In addition, the combination of a
      large head and a highly crosslinked polyethylene has allowed a new form of
      constrained acetabular component to be designed. This many be another advance in
      terms of the problems of recurrent dislocation.

PMID- 14584313
TI  - Total hip arthroplasty using femoral head shelf autografts in dysplastic hips.
      Our experience.
AB  - The present work deals with a series of 28 patients (a total of 31 hips)
      suffering from coxarthrosis in dysplasia of the hip. All patients had undergone
      arthroplasty where an autograft of cortico-cancellous bone was taken from the
      head of the patientis femur. In 21 of these hips the prosthetic components were
      not cemented while the other 10 cases were. The patients (average age 57 years 5
      months) underwent radiography and were clinically evaluated using the Harris Hip
      Score. The average follow-up was 6 years and 7 months. In the 10 hips which had
      been cemented, the average pre-operative Harris Hip Score was 46.9 points (range
      24-85) while it was 80.5 upon check-up (range 50-98). In the 21 hips which were
      not cemented the average pre-operative Harris Hip Score was 44.3 points (range 21
      62) while, at the time of check-up it was 90.8 (range 60-100). Only in 3 cases
      (9.67%) did the cotyloid portion require reoperation because of mobilization. In
      all cases (100%) the graft integrated perfectly with the host bone. The present
      study provides encouraging data regarding the use of autografts of cortico
      cancellous bone taken from the head of the femur during hip replacement in
      patients with coxarthrosis in dysplasia of the hip. No differences were seen
      between the cemented and non cemented prostheses.

PMID- 14584314
TI  - Hip surgery in cerebral palsy.
AB  - The authors report the importance of hip dislocation and pelvic imbalance in
      patients with cerebral palsy, as the cause of pain, decubitus, and severe
      secondary deformities of the vertebral column. They report their experience in
      the surgical treatment of spastic hip, based on 231 cases with a mean follow-up
      of 5.4 years. The authors emphasize the importance of obtaining a balanced pelvis
      to allow for walking and sitting in the severest patients, and in order to avoid
      severe deformity of the vertebral column. The surgical methods used, with
      particular interest in the importance of stabilizing reduction by
      intertrochanteric osteotomies of the femur and/or acetabular roof osteotomies,
      are described. Results obtained, positive in 88% of cases, are also reported.

PMID- 14584315
TI  - New cell-based technologies in bone and cartilage tissue engineering. I. Bone
      reconstruction.
AB  - A tissue engineering, cell-based therapeutic approach could be essential for
      extensive bone or cartilage reconstruction. This article is divided in two
      chapters and describes new cell-based surgical techniques for cartilage and bone
      reconstruction. In the first part on bone reconstruction, marrow-derived
      osteogenic progenitor cells combined with hydroxyapatite were utilized. The
      validity of this model has been shown for the repair of critical size bone
      defects in large size animal models. We used this cell-based therapeutic approach
      to treat 3 patients with large bone defects, achieving bone reconstruction.

PMID- 14584316
TI  - Flat foot: a comparison of surgical methods.
AB  - The authors present a comparative review of cases concerning the results obtained
      in the treatment of idiopathic flat foot: the methods compared were Castaman
      exosinotarsal arthrorisis and Giannini endosinotarsal arthrorisis. Between 1990
      and 1198 a total of 80 patients, of which 40 with calcaneo-stop, and 40 with
      Giannini screws, were submitted to surgery at the Orthopaedic and Traumatology
      Department of the University of Rome "La Sapienza". The clinical, radiographic
      and functional results were classified as good, fair and poor. The authors agree
      on the effectiveness of both methods based on the results obtained and the
      facility of implantation techniques, however emphasizing the minor injury of the
      anatomical structures of the subtalar joint when the calcaneo-stop method with
      Castaman conical screws was used.

PMID- 14584317
TI  - The Fixion expansion nail in the surgical treatment of diaphyseal fractures of
      the humerus and tibia. Our experience.
AB  - The authors present their experience in the application of a Fixion expansion
      intramedullary nail for the treatment of diaphyseal fractures of the humerus and
      tibia, in a total of 40 surgeries. The features of the nail are: stability and
      flexibility of the instrumentation, speed of surgery, minimal exposure to
      radiation. The results obtained up to now are encouraging; there are no
      significant problems either during or after surgery, and mean consolidation time
      is 3 months for fractures of the humerus, and 4 months for those of the tibia.
      The Fixion nail is a versatile type of instrumentation that is easy to use.

PMID- 14584318
TI  - The normalization of data in the Constant-Murley score for the shoulder. A study
      conducted on 563 healthy subjects.
AB  - The study was conducted in order to evaluate the theoretical design of the
      Constant-Murley system and to reveal any difficulties in obtaining data when it
      is used in 563 subjects not affected with shoulder pathology. The total mean
      score for the subjects examined was 85.2 points (minimum 75, maximum 100 points).
      Values revealed a decreasing trend beginning at 50 years of age for men and 30
      for women. Only 4 subjects achieved a maximum score of 100. The measurements
      taken allowed us to elaborate a reference table based on sex and age, which was
      required to calculate the correct score. These values differ from those reported
      by the inventors of the system and they reveal the need to compile personal
      tables for the normalization of scores.

PMID- 14584319
TI  - Viscoelastic properties of the semitendinosus and gracilis tendons in
      reconstruction of the ACL: an in vivo evaluation.
AB  - Tensioning of the tendons of the semitendinosus and the gracilis used to
      reconstruct the anterior cruciate ligament (ACL) of the knee is one of the main
      factors to take into consideration during surgery that aims at obtaining good
      postoperative joint stability. Some authors have shown in vitro that the
      viscoelastic nature of the patellar tendon is responsible for its gradual release
      (loss of tension). It is the purpose of this study to verify in vivo the
      biomechanical behavior of the semitendinosus and gracilis tendons. A total of 40
      consecutive patients were submitted to reconstruction of the ACL with flexor
      tendons of the knee using a method that allows for the gradual tensioning of the
      doubled semitendinosus and gracilis tendons using the Swing Bridge method.
      Patients were divided into 2 groups: in the first 20 patients (group I), after
      adequate manual pretensioning and tibial and femoral stabilization, the tendons
      were twisted using a dynamometer to measure torsion forces until tensioning equal
      to 2.5 N was achieved. The control group (group II) was made up of the successive
      20 patients in whom tensioning of the tendons at 2.5 N was carried out in many
      phases. Five minutes after initial tensioning at 2.5 N the decrease in tension
      was recorded that returned to initial values. A similar procedure was carried out
      after 5 more minutes. The patients in both groups were evaluated using a KT-1000
      arthrometer one year after surgery. The patients in group II showed a decrease in
      torsion equal to 37.2% after the first 5 minutes, and a further 26.8% after 5
      more minutes, and measurement by means of KT-1000 revealed mean values for S/S 30
      lb. and S/S MM of 1.3 mm and 1.7 mm, respectively, that proved to have a
      statistically significant difference (p < 0.05) as compared to the patients in
      group I (S/S 30 lb.: 2.0 mm; S/S MM: 2.4 mm). Although these data do not provide
      indications on the amount and duration of pretensioning and definitive tensioning
      to be applied to the transplant, they do clearly show the viscoelastic properties
      of the tendons. These properties require a more in-depth study to better
      determine the exact tensioning of the neoligament.

PMID- 14584320
TI  - Vertebral localization of a brown tumor: description of a case and review of the
      literature.
AB  - The authors report a case of a female aged 45 years submitted to a long period of
      hemodialysis, affected with brown tumor of the lumbar spine. Brown tumor must be
      taken into consideration in the differential diagnosis of osteolytic lesions of
      the skeleton, particularly in young, nephropathic women undergoing hemodialysis.
      Brown tumor has a more favorable prognosis as compared to other lesions that have
      similar clinical and radiographic findings, such as metastatic lesions and giant
      cell tumors. In the case of brown tumor, in addition to treating lesion of the
      spine, treatment varying depending on neurological findings and biomechanical
      complications (structural collapse, segmental kyphosis, pathologic fracture,
      etc.), removal of the parathyroids and correction of the metabolic alterations is
      indispensable.

PMID- 14584321
TI  - Mycobacterium marinum: a case of skin granuloma complicated by tenosynovitis of
      the extensors.
AB  - The authors report the case of a male patient who owned a tropical aquarium and
      who developed a M. marinum skin infection of the wrist. The clinical findings and
      microbiological features of the case are described, as are the difficulty in
      providing a prompt diagnosis, and the need for surgical treatment and the use of
      antibiotics to treat the infection.

PMID- 14584322
TI  - Mixing politics with pleasure. An AHA vice president organizes a fund-raiser for
      the Bush-Cheney campaign. Does this constitute a conflict of interest?
AB  - An American Hospital Association lobbyist's fund-raiser for the Bush-Cheney re
      election campaign last week at Washington's Capitol Hill Club raised eyebrows,
      along with questions about the gray area between personal advocacy and the
      industry's political agenda. The AHA was not involved in the event, association
      officials say, but some observers remain skeptical.

PMID- 14584323
TI  - Up in arms--for now. Rise in uninsured draws immediate reaction.

PMID- 14584324
TI  - NQF offers nursing criteria.

PMID- 14584325
TI  - Funding fight. Campaign seeks to boost indirect education payments.

PMID- 14584326
TI  - Branching out. Newly renamed HPA to enter acute-care market.

PMID- 14584327
TI  - Deadline dash in Ohio. Legislative limit on specialty hospitals may backfire.

PMID- 14584328
TI  - In the crossfire. Missouri hospitals ready defenses against law allowing
      concealed weapons.

PMID- 14584329
TI  - Mass exodus. Oregon's Regence to drop traditional HMO.

PMID- 14584330
TI  - Before breaking ground, take stock. Spending millions on a new hospital won't fix
      a dysfunctional organization.

PMID- 14584331
TI  - Style and substance. Winners in Design Awards offer capacity to adapt.

PMID- 14584332
TI  - Committed commuter. MedPAC's chairman lives far from D.C., but he's never far
      removed from the business of Medicare.

PMID- 14584333
TI  - How to eat smarter.

PMID- 14584334
TI  - At last, the pill for men.

PMID- 14584335
TI  - Never trust a tiger.

PMID- 14584336
TI  - Fessing up to fats.

PMID- 14584337
TI  - Spa kids.

PMID- 14584338
TI  - A doctor's duty.

PMID- 14584339
TI  - How the Supremes redeemed Bush.

PMID- 14584340
TI  - A yea for gays.

PMID- 14584341
TI  - Will this experiment work?

PMID- 14584342
TI  - Bzzzz ... slap!

PMID- 14584343
TI  - More than just olive oil.

PMID- 14584344
TI  - Asthma: epidemiology, burden, and quality of life.

PMID- 14584345
TI  - The historical catalyst to cure asthma.

PMID- 14584346
TI  - Depression in patients with asthma.

PMID- 14584347
TI  - Asthma and anxiety disorders.
AB  - In this chapter we have reviewed recent findings on the co-occurrence of asthma
      and anxiety disorders in youth and adults in clinical and community-based
      samples. We have not included a review of research on linkages between
      respiratory functioning and anxiety symptoms, or the linkages between asthma
      severity and anxiety symptoms, though several recent reviews of these areas are
      available [see 5, 12]. If possible, future research is needed to disentangle the
      relationship between asthma and anxiety disorders compared with that with other
      medical conditions. This may involve using samples that are unselected for either
      disorder of interest, including population samples where a range of severity is
      present. Studies that document a relationship between asthma and an increased use
      of emergency room services for asthma do not indicate that there is a link
      between asthma and anxiety disorders, but may simply reflect a relationship
      between mental disorders, which is well-documented, or an association being
      driven by a common third factor, such as low socioeconomic status, which is
      linked to both. There are also numerous studies that have investigated the
      relationship between anxiety symptoms and anxiety disorders and severity, use of
      treatment, and other clinical correlates of asthma and anxiety, especially panic
      [see 5 for a review], but a review of this literature is beyond the scope of this
      chapter. Results of studies to date suggest a link between asthma and anxiety
      disorders among both youth and adults, and in clinical and community-based
      samples. Still, many questions about this association remain unanswered. Future
      work is needed to determine the strength and specificity of the link between
      asthma and anxiety disorders. The temporal relationship between the onset of
      asthma and anxiety disorders, and relatedly, the mechanism of this association is
      also poorly understood. Furthermore, there is mounting evidence of a potential
      familial relationship between asthma and anxiety disorders, which warrants
      further investigation, and if replicated it will be important to uncover the
      mechanism of this association. Another unexplored area is common environmental
      factors, as emerging evidence suggests that there may be shared risk factors for
      both asthma and anxiety disorders in youth (e.g., urban residence, parental
      smoking), and future investigations into this link seem promising. In addition,
      studies that investigate the linkages between use of specific medications for
      asthma and the onset of anxiety symptoms and anxiety disorders are needed, both
      looking at the short- and long-term effects. As there is increasing data that use
      of specific medications are associated with brain changes, mood and psychotic
      disorders [41], and there is also emerging evidence of a link between asthma and
      respiratory disease and suicidal ideation and suicide attempts [42], further
      investigation into this area is important. Work is currently underway aimed at
      improving our understanding of the etiology and modifiable risk factors for onset
      and persistence of the co-occurrence of asthma and anxiety disorders, and the
      nature of the relationship between the two has the potential to lead to
      significant improvements in the understanding of etiology and effectiveness of
      treatment for both, as well as primary and secondary prevention efforts, among
      youth and adults in the community. The public health significance of both asthma
      and anxiety disorders, especially with a substantial increase in asthma, and
      possibly anxiety disorders [13], over the past two decades, highlights the
      potential import of work aimed at understanding these linkages.

PMID- 14584348
TI  - Psychiatric syndromes that mimic asthma.

PMID- 14584349
TI  - A model for changing human health behavior: application to asthma management.

PMID- 14584350
TI  - Provider and patient adherence with asthma evaluation and treatment.

PMID- 14584351
TI  - Symptom perception in chronic asthma: learning for better or worse?

PMID- 14584352
TI  - Emotions and family factors in childhood asthma: psychobiologic mechanisms and
      pathways of effect.

PMID- 14584353
TI  - Effects of prescription corticosteroids on mood and memory.

PMID- 14584354
TI  - Key developments in orthopaedics.

PMID- 14584355
TI  - Managing osteoarthritis.

PMID- 14584356
TI  - Casebook: chronic knee pain.
AB  - It is beyond the scope of this article to fully explore the many and varied
      causes of chronic knee pain, but we hope to have reminded the reader of some of
      the essential principles involved. The importance of a full history cannot be
      over-emphasised and particular attention should be paid to issues surrounding the
      mechanism of injury and the role of a patient's chosen sport in their life. The
      cases highlight the value of the involvement of a multi-disciplinary team
      including physiotherapists, podiatrists and dieticians. It is also usual to
      involve sports psychologists and team coaches/trainers at the higher levels of
      sport. An appreciation of normal biomechanics is necessary. There are several
      specialised tests used in the evaluation of knee pain and it is worthwhile
      spending some time with a physiotherapist or colleague with an interest in
      musculoskeletal medicine to learn and practice them.

PMID- 14584357
TI  - Prescribing NSAIDs in practice.

PMID- 14584358
TI  - Common problems of the hand and wrist.

PMID- 14584359
TI  - Current thinking in atopic eczema.

PMID- 14584361
TI  - Overview of the MRCGP exam.

PMID- 14584360
TI  - Re: Managing hypertension, the Practitioner, September 2003-09-09.

PMID- 14584362
TI  - Common themes in changing vector-borne disease scenarios.
AB  - The impact of climate change on disease patterns is controversial. However,
      global burden of disease studies suggest that infectious diseases will contribute
      a proportionately smaller burden of disease over the next 2 decades as non
      communicable diseases emerge as public health problems. However, infectious
      diseases contribute proportionately more in the poorest quintile of the
      population. Notwithstanding the different views of the impact of global warming
      on vector-borne infections this paper reviews the conditions which drive the
      changing epidemiology of these infections and suggests that such change is linked
      by common themes including interactions of generalist vectors and reservoir hosts
      at interfaces with humans, reduced biodiversity associated with anthropogenic
      environmental changes, increases in Plasmodium falciparum: P. vivax ratios and
      well-described land use changes such as hydrological, urbanization, agricultural,
      mining and forest-associated impacts (extractive activities, road building,
      deforestation and migration) which are seen on a global scale.

PMID- 14584363
TI  - Methodological problems and amendments to demonstrate effects of temperature on
      the epidemiology of malaria. A new perspective on the highland epidemics in
      Madagascar, 1972-89.
AB  - There is a growing consensus that changes in climate will have major consequences
      for human health through a reduction in the availability of food and an
      increasing frequency of natural disasters. However, the contribution of higher
      temperatures to vector-borne diseases, particularly malaria, remains
      controversial despite the known biological dependence of both vector and pathogen
      on climate. Misconceptions and inappropriate use of variables and methods have
      contributed to the controversy. At present there appears to be more support for
      non-climatic explanations to account for the resurgence of malaria in the African
      highlands, e.g. the deterioration of malaria control and the development of drug
      resistance. An attempt is made here to show that dismissing temperature as a
      driving force in the case of malaria is premature. Using a de-trended time-series
      of malaria incidence in Madagascar between 1972 and 1989 indicated that a minimum
      temperature during 2 months at the start of the transmission season can account
      for most of the variability between years (r2 = 0.66). These months correspond
      with the months when the human-vector (Anopheles gambiae sensu lato) contact is
      greatest. The relationship between El Nino Southern Oscillation (ENSO) and
      temperature (r = 0.79), and ENSO and malaria (r = 0.64), suggests that there
      might be an increased epidemic risk during post-Nino years in the Madagascar
      highlands and therefore warrants increased vigilance and extended control efforts
      in the first half of 2003. This review suggests that the rejection of climate
      disease associations in studies so far published may not have used biologically
      relevant climate parameters. It highlights the importance of identifying more
      relevant parameters during critical periods of the transmission season in order
      to aid epidemic forecasting and to assess the potential impact of global warming.

PMID- 14584364
TI  - Climate change, conflict and health.
AB  - Both conflict and climate change may produce serious negative health
      consequences. However, there is insufficient evidence that climate change, e.g.
      through environmental degradation or fresh water shortages, leads to conflict as
      is often claimed. Also, current theory on cause of conflict would refute this
      hypothesis.

PMID- 14584365
TI  - Domestic dog ownership: a risk factor for human infection with Leishmania
      (Viannia) species.
AB  - An epidemiological study has shown that cumulative, village prevalence of
      Leishmania (Viannia) infection in dogs ranges from 8% to 45% in Huanuco, Peru.
      Using data from a prospective survey of human American cutaneous leishmaniasis
      (ACL) collected during 1994-98, it was shown that the village-level risk of human
      ACL did not significantly increase with dog abundance, neither in absolute terms
      (P = 0.659) nor in relation to dog:human ratios (P = 0.213). A significant
      positive association was observed between risk of human ACL and village dog ACL
      prevalence (P = 0.022). When controlled for village dog ACL prevalence, there
      also was an association between the average number of dogs per household and risk
      of human ACL (P = 0.033). The results suggest that dogs play a role in the
      (peri)domestic transmission of Le. (Viannia) to humans in Huanuco and indicate
      that a control intervention targeting dogs to control human ACL is warranted.

PMID- 14584366
TI  - Schistosomiasis control in Ghana: case management and means for diagnosis and
      treatment within the health system.
AB  - An essential component of integrated schistosomiasis control as promoted by WHO
      is adequate clinical care for patients presenting at health care facilities. We
      evaluated the functioning of the Ghanaian health system for diagnosis and
      treatment of schistosomiasis by interviewing health workers from 70 health care
      facilities in 4 geographical areas in April and May 2000. Results from
      presentation of 4 hypothetical cases and a subsequent interview demonstrated that
      patients presenting with symptoms related to schistosomiasis have a small chance
      of receiving adequate treatment: often health workers do not recognize the
      symptoms, especially those of Schistosoma mansoni; patients are frequently
      referred for a diagnostic test or treatment with a large risk of non-compliance;
      and praziquantel was not available in 78% of the health care facilities with
      reported schistosomiasis in their coverage area. The overall cost of treatment is
      considerable: [symbol: see text] 2.13 for S. haematobium and [symbol: see text]
      1.81 for S. mansoni patients, with drug costs contributing approximately 40% of
      the total cost. To better meet WHO recommendations for passive case detection as
      part of integrated schistosomiasis control, the Ghanaian health system needs to
      emphasize training of health workers in schistosomiasis case recognition and case
      management and increase the availability of praziquantel. Experience from other
      West African countries indicate that this is feasible.

PMID- 14584367
TI  - Impact of drainage and sewerage on diarrhoea in poor urban areas in Salvador,
      Brazil.
AB  - A longitudinal prospective study of the effect of drainage and sewerage systems
      on diarrhoea in children aged < 5 years was conducted in 9 poor urban areas of
      the city of Salvador (population 2.44 million) in north-east Brazil in 1989-90.
      Due to complex political and administrative reasons, 3 areas had benefited from
      drainage improvements, 3 from both drainage and sewerage improvements, and 3 from
      neither. An extensive questionnaire was applied to collect information on each
      child and on the conditions of the household, and mothers recorded diarrhoea
      episodes in their children aged < 5 years daily for 1 year, using calendars.
      Fortnightly home visits were made to collect the data. The incidence of diarrhoea
      in children in neighbourhoods with drainage was less than two-thirds, and in
      neighbourhoods with drainage and sewerage less than one-third, of the incidence
      in neighbourhoods with neither. After controlling for potential confounders, the
      proportion of children with 'frequent diarrhoea' showed the same significant
      trend across the study groups. Though the groups were not exactly comparable,
      more than one child was monitored per household, and it was not possible to
      rotate fieldworkers between study groups, the study provides evidence that
      community sanitation can have an impact on diarrhoeal disease, even without
      measures to promote hygiene behaviour.

PMID- 14584368
TI  - An outreach education and treatment project in Ghana for the early stage of
      Mycobacterium ulcerans disease.
AB  - Mycobacterium ulcerans disease starts as a painless, subcutaneous nodule,
      excision of which prevents the development of large Buruli ulcers. An outreach
      programme was set up in Ghana to promote nodule recognition and excision. The
      programme was cost-effective and shifted the pattern of disease presentation.
      This could from a model for other countries.

PMID- 14584369
TI  - Cognitive performance at school entry of children living in malaria-endemic areas
      of Sri Lanka.
AB  - In a cross-sectional study, carried out in January 1997 at the beginning of the
      school year, the impact of repeated attacks of malarial infection on the
      cognitive performance of children at school entry in moderate malaria-endemic
      areas of Sri Lanka was investigated. The cognitive performance of 325
      schoolchildren in grade 1 (mostly aged 5-6 years) in 2 districts of Sri Lanka
      which are endemic for malaria (Anuradhapura and Moneragala) was assessed by an
      entry performance test developed by the National Institute of Education, Sri
      Lanka. The indices assessed included writing, language and mathematical skills.
      There was no difference in any of the cognitive performance indices between
      children from Anuradhapura and Moneragala districts. The scores of most of the
      indices decreased as the number of malaria infections experienced by a child
      increased and the ability to identify letters was significantly impaired by the
      number of malaria infections a child had experienced after controlling for socio
      economic and nutritional status. These findings suggests that repeated attacks of
      malaria in children can have an adverse impact on their development.

PMID- 14584370
TI  - Case report: the first parasitologically confirmed autochthonous case of acute
      Chagas disease in Suriname.
AB  - We present a case report from 2001 of the first parasitologically confirmed case
      of acute Chagas disease in Suriname. The patient had never left Suriname, and was
      probably infected by an adventitious species of Panstrongylus in his house in the
      capital city, Paramaribo. The patient was treated with nifurtimox, and appears to
      have recovered.

PMID- 14584371
TI  - Leishmania major and HIV co-infection in Burkina Faso.
AB  - The incidence of cutaneous leishmaniasis (CL) has increased in Ouagadougou,
      Burkina Faso since 1996. A study was carried out from September to November 2000
      to determine the impact of HIV on this outbreak. Of 74 CL patients, 10 were co
      infected with HIV. The percentage of CL in patients positive for HIV was slightly
      higher than the percentage of HIV patients in Ouagadougou. However, the study
      showed that HIV infection did not increase the risk of CL infection.

PMID- 14584372
TI  - The prolonged epidemic of anthroponotic cutaneous leishmaniasis in Kabul,
      Afghanistan: 'bringing down the neighbourhood'.
AB  - In order to investigate the distribution and causes of the spread of
      anthroponotic cutaneous leishmaniasis (ACL) in Kabul, Afghanistan, a cross
      sectional study was conducted during 1997-98 amongst 75,787 residents in the 13
      central districts of the city. Using data on active lesions and scars with their
      times of onset, migration patterns and age of subjects, 2 independent methods
      were used to estimate, retrospectively, the annual incidence of ACL in recent
      years. Results indicated a rapid increase in incidence from 1987, peaking in 1996
      when an estimated 12% of the population had active disease. Active prevalence was
      lowest in infants (aged < 2 years), and while risk was gender-independent in
      children and adolescents, active prevalence in those aged > 20 years was
      significantly higher amongst females than males (odds ratio [OR] = 1.51, 95% CI
      1.34-1.70). About 44% of lesions were located on the head, 38% on upper limbs,
      16% on lower limbs and 2% elsewhere. The relative frequency of head lesions
      dropped with age (P < 0.001), and amongst adults was lowest amongst males (P <
      0.001), possibly due to the protective effect of a beard. Within the study
      population, 32% reported that they had immigrated from outside Kabul, 34% that
      they had been born in Kabul but had since migrated to another district of the
      city, and 34% that they had been born in the district of their present residence.
      Active prevalence amongst those born in their current district of residence was
      positively associated with the percentage of immigrants in their district (P =
      0.027), indicating that a 1% increase in the percentage of immigrants increased
      the odds of an active lesion by 12% (OR = 1.12, 95% CI 1.01-1.24), but there was
      no association with the percentage of migrants from other districts in Kabul (P =
      0.65) or with war damage (P = 0.33). As active prevalence was not significantly
      greater in immigrants than local Kabulis, these results support the hypothesis
      that the epidemic in Kabul has been maintained by a steady influx of susceptible
      immigrants. It is important that the new opportunities for social development
      that now exist in Kabul are not hampered by this unpleasant and stigmatizing
      disease. As population movement is clearly a contributing factor to its
      transmission, this threat is very real.

PMID- 14584373
TI  - Epidemiological and morbidity assessment of Schistosoma japonicum infection in a
      migrant fisherman community, the Dongting Lake region, China.
AB  - We assessed the epidemiology and morbidity related to Schistosoma japonicum
      infection by both parasitological (Kato-Katz method and miracidium hatching test)
      and ultrasound examination in a migrant fisherman community (n = 106) from the
      Dongting Lake region in China in 2001. A prevalence of 69.8% and a mean infection
      intensity of 66.5 eggs per gram (epg) were recorded for this group. Males had a
      higher level of infection (77%) and intensity (92.2 epg) compared with females
      (58% and 28.6 epg, respectively). Subjects aged 11-20 years had the highest
      prevalence of infection (91%) and the heaviest infection intensity (85.3 epg)
      among all age groups. Twenty-six percent of the subjects had not been treated
      previously for schistosomiasis. Parenchymal fibrosis (> or = stage II) detected
      by ultrasound and spleen enlargement (or splenectomy) occurred in 37% and 9% of
      subjects, respectively. Portal vein dilation was detected in 18% subjects, and
      58% (11/19) of those patients with portal vein enlargement were shown to have
      parenchymal fibrosis (> or = stage II). These results indicate that S. japonicum
      infection and related morbidity in mobile fisherman is still unacceptably high
      despite the fact that China has implemented a Schistosomiasis Control Project
      financed by a World Bank Loan for a period of 8 years since 1992. Clearly, new
      approaches for schistosomiasis control, especially in communities like these
      mobile fishermen, should be explored.

PMID- 14584374
TI  - Heterogeneity in the prevalence and intensity of loiasis in five contrasting
      bioecological zones in Cameroon.
AB  - The prevalence and intensity of loiasis were studied in 4532 individuals selected
      from 42 villages from 5 contrasting bioecological zones in Cameroon from February
      to July 2001. The individuals were examined for Loa loa microfilaraemia using the
      thick blood film method. Loiasis was heterogeneously distributed from one
      bioecological zone to another. The occurrence of the infection was largely
      related to environmental factors favouring the breeding of Chrysops vectors. The
      mean prevalence of infection varied from 0% in the grassland savannah, 6.6% in
      the deciduous equatorial rainforest, 9.7% in the dense-humid equatorial
      rainforest, to 33.3% in the forested savannah. Loiasis was totally absent in the
      grassland savannah. The intensity of loiasis infection (L. loa microfilariae per
      millilitre [mf/mL] of blood) increased with an increase in prevalence, varying
      from 0 mf/mL in the grassland savannah, 325 mf/mL in the deciduous equatorial
      rainforest, 433 mf/mL in the dense-humid equatorial rainforest, to 3125 mf/mL in
      the forested savannah. The proportion of individuals with high (> 8000 mf/mL) and
      very high (> 30,000 mf/mL) L. loa microfilaraemia was greater in bioecological
      zones with a higher prevalence of L. loa. These results will be valuable for the
      prediction of loiasis endemicity in different ecological zones of Central Africa
      and for the refinement of the existing geographical model for the mapping of
      loiasis.

PMID- 14584375
TI  - Geographic Information System mapping of snakebite incidence in northern Ghana
      and Nigeria using environmental indicators: a preliminary study.
AB  - Snakebite is an important health problem in many parts of rural West Africa where
      the carpet or sawscaled viper, Echis ocellatus, is responsible for most of the
      morbidity and mortality. Marked seasonal and geographical variation in the
      incidence of snakebite suggests an association with environmental factors that
      could potentially identify high-risk areas and inform health care decision
      making. This preliminary investigation describes a Geographic Information System
      (GIS) approach to risk mapping that identifies environmental variables
      potentially associated with variation in snakebite incidence rates at a number of
      health facilities in northern Ghana and Nigeria and which has been used to create
      a preliminary risk map of the potential probability of high snakebite incidence
      for West Africa. Detailed and extensive further studies will enable the more
      reliable estimation of snakebite incidence at a local level across the region.

PMID- 14584376
TI  - Epidemiological and clinical aspects of blackwater fever among African children
      suffering frequent malaria attacks.
AB  - Blackwater fever (BWF), one of the commonest causes of death of Europeans living
      in Africa at the beginning of the twentieth century, but rarely diagnosed since
      the 1950s, is related to Plasmodium falciparum malaria but there is considerable
      debate and controversy about its aetiology. From 1990 to 2000, the whole
      population of Dielmo, a village in Senegal, was involved in a prospective study
      of malaria. Three cases of BWF occurred in 3 children aged 4, 7 and 10 years,
      belonging to a subgroup of children who suffered malaria attacks every 4 to 6
      weeks over many years, who had received repeated quinine treatment. The spread of
      chloroquine resistance, by increasing the use of more toxic alternative drugs,
      may expose endemic populations to a high incidence of severe side effects of
      antimalarials.

PMID- 14584377
TI  - Increased frequency of malaria attacks in subjects co-infected by intestinal
      worms and Plasmodium falciparum malaria.
AB  - The influence of intestinal worm infections on malaria was studied in individuals
      from Dielmo, Senegal in 1998. Results suggest that, compared with those infected,
      individuals free of helminths had the same degree of protection against malaria
      as that provided by sickle-cell trait, the most potent factor of resistance to
      malaria identified to date.

PMID- 14584378
TI  - Imported cutaneous gnathostomiasis: report of five cases.
AB  - Gnathostomiasis has rarely been described outside endemic countries. We report on
      a series of 5 patients (4 females, 1 male, mean age 42.2 years) who returned to
      France from South-East Asia and presented with cutaneous gnathostomiasis. The
      cutaneous lesions appeared within a mean period of 62 d (range 10-150 d) after
      return. They consisted of creeping eruptions in 3 patients (in addition one also
      had papules, one had nodules and hepatitis, and one had hepatitis; all 3 had
      profound asthenia) and recurring migratory swellings in 2 patients. The mean
      eosinophil count was 1546/mm3 (range 398-3245/mm3). Diagnosis was based on
      positive serological tests in 3 patients and seroconversion in 2 patients, and
      was confirmed by identification of Gnathostoma hispidum in a biopsy specimen from
      one of the seropositive patients. Albandazole (1-4 courses) was given as
      treatment. Recurrences may occur up to 24 months after apparent cure without
      reinfection. Gnathostomiasis should be considered when patients return from
      tropical countries and present with migratory swellings or creeping eruption that
      does not respond to the usual treatment for cutaneous larva migrans. Serological
      tests may be negative initially and thus need to be repeated to check for
      seroconversion. Treatment may require multiple courses of albendazole and a
      prolonged period of follow-up is necessary before cure can be confirmed.

PMID- 14584379
TI  - Classification, follow-up and recurrence of hepatic cystic echinococcosis using
      ultrasound images.
AB  - Ultrasound image and morphological structure of hepatic cystic echinococcosis
      (CE) were analysed in 277 human cases (385 hepatic hydatid cysts). These included
      65 CE cases from community surveys carried out between 1995 and 2000 in 3
      countries (China, Mongolia and Jordan) and 212 cases from a clinical hospital
      survey from Xinjiang, China. A new simplified WHO ultrasound classification for
      human CE was assessed, and considered useful. It is proposed that type, size and
      number in particular need to be included in the ultrasound classification of
      hepatic CE. For comparative purposes 6 categories of type were classified in the
      study as Type 0 to Type 5 (T0-T5): T0, univesicular without pathognomonic signs;
      T1, univesicular with pathognomonic signs; T2, cysts with sagging or floating
      laminated membrane; T3, cysts containing daughter cysts; T4, solid mass or mixed
      cysts; and T5, cysts with partial or full calcifications. This differs from the
      WHO classification wherein Type T3 cysts (daughter cysts present) are considered
      a pathological stage to occur in general prior to the sagging or floating
      membrane (T2) stage. Recurrent hydatid cysts in the liver were also studied based
      on morphological structures observed directly from surgical intervention. Case
      follow-up over 1-5 years since endocystectomy in the community surveys indicated
      10% (2/10) recurrence of cysts in the residual surgical cavity. Recurrent CE
      included 2 (2/4) cases after percutaneous treatment.

PMID- 14584380
TI  - Subclinical mastitis among HIV-infected and uninfected Zimbabwean women
      participating in a multimicronutrient supplementation trial.
AB  - Subclinical mastitis, defined as raised milk sodium/potassium (Na/K) ratio is
      common and associated with poor infant growth and increased mother-to-child HIV
      transmission. In 1996-97, we conducted a randomized controlled trial of multiple
      micronutrient supplementation, at recommended daily allowance levels, from 22 to
      35 weeks gestation until 3 months post-partum, on the prevalence and severity of
      subclinical mastitis among 84 HIV-infected and 83 HIV-uninfected lactating
      Zimbabwean women and on their infants' growth. Spot milk samples collected before
      4.5 months post-partum were analysed for Na/K ratio by flame photometry. There
      was no significant difference in prevalence of subclinical mastitis between HIV
      infected and HIV-uninfected women. After controlling for infant age at time of
      sampling, micronutrient-supplemented HIV-infected women had non-significantly (P
      = 0.08) lower geometric mean Na/K ratio (0.43, 95% CI 0.35-0.51) than HIV
      infected women given placebo (0.51, 95% CI 0.42-0.61). Micronutrient
      supplementation had no effect on the prevalence of subclinical mastitis among HIV
      uninfected women (odds ratio [OR] = 1.26, 95% CI 0.45-3.51, P = 0.80) but induced
      a borderline decrease in prevalence (OR = 2.82, 95% CI 0.96-8.26, P = 0.07) among
      HIV-infected women. Infant weight between 1.5 and 4.5 months was lower in women
      with higher milk Na/K ratio. Thus, the importance of subclinical mastitis for
      infant growth suggests that further investigations to decrease the condition,
      perhaps using higher micronutrient doses, are warranted.

PMID- 14584381
TI  - The effect of mass administration of sulfadoxine-pyrimethamine combined with
      artesunate on malaria incidence: a double-blind, community-randomized, placebo
      controlled trial in The Gambia.
AB  - A double-blind, community-randomized, placebo-controlled trial was conducted in a
      rural area of The Gambia between June and December 1999 to test whether a
      reduction in the infectious reservoir can reduce malaria transmission. Overall
      14,017 (85%) individuals living in the study area were treated with either
      placebo or sulfadoxine-pyrimethamine (SP) combined with a single dose of
      artesunate (AS). Following the mass drug administration (MDA) 1375 children aged
      6 months to 10 years were kept under surveillance for clinical malaria in 18
      villages throughout the 1999 malaria transmission season. During a 20-week
      surveillance period 637 episodes of malaria were detected. The mean incidence
      rate was 2.5/100 child-weeks in the placebo villages, and 2.3/100 child-weeks in
      villages that received SP + AS. The mean rate ratio, adjusted for individual and
      village-level covariates, was 0.91 (95% CI 0.68-1.22, P = 0.49). During the first
      2 months of surveillance, the malaria incidence was lower in treated villages.
      After 2 months the incidence was slightly higher in the MDA group but this was
      not statistically significant. Overall, no benefit of the MDA could be detected.
      The reason for the absence of an impact on malaria transmission is probably the
      very high basic reproductive number of malaria, and the persistence of mature
      gametocytes, which are not affected by AS treatment.

PMID- 14584382
TI  - Changes in susceptibility of Plasmodium falciparum to artesunate in vitro in
      Yunnan Province, China.
AB  - We investigated changes in the susceptibility of Plasmodium falciparum to
      artesunate in vitro using Rieckmann's microtest in Yunnan Province, China, during
      the period 1988 to 1999. Longitudinal surveillance studies in 1988, 1992 and 1999
      revealed that the IC50s were 6.2, 7.2 and 20.7 nmol/L, respectively and mean
      concentrations completely inhibiting schizont formation (CIMC) were 37.8, 46.1
      and 74.0 nmol/L, respectively. The IC50 and CIMC in 1999 were 3.3 and 2 times
      greater than in 1988. In cross-sectional tests from 1991 to 1993, the
      susceptibility of P. falciparum isolates from areas in the western and the
      southern parts of Yunnan Province were similar, but lower than in the south
      eastern and central parts of the province. The results suggest that P. falciparum
      is generally susceptible to artemisinin derivatives but indicate a reduction in
      susceptibility during the study period in areas where the drugs have been used
      for a long time.

PMID- 14584384
TI  - Involvement of interleukin-18 in severe Plasmodium falciparum malaria.
AB  - Serum levels of interleukin-18 (IL-18), interferon-gamma (IFN-gamma), and
      immunoglobulin E (IgE) were determined for 96 patients with Plasmodium falciparum
      malaria admitted to hospital, Bangkok, Thailand in the period 1998-2000. The
      patients were divided into 3 groups, i.e. uncomplicated, severe and cerebral
      malaria according to WHO criteria (2000). Elevation of IL-18 levels was observed
      in all 3 groups, with a tendency for higher levels in cases with severe malaria
      throughout the course of the disease. Moreover, there was a significant
      correlation between IL-18 levels and the extent of parasitaemia among patients
      with severe malaria. However, IL-18 levels decreased more significantly in
      patients with cerebral malaria compared with the other groups in the late stage
      of the disease. Elevated levels of IFN-gamma were also observed in all groups of
      patients, especially in those with severe or cerebral malaria, and the levels in
      patients with cerebral malaria remained significantly higher than in those with
      uncomplicated malaria during days 4-7 post-treatment, suggesting the involvement
      of IFN-gamma in disease severity. Meanwhile, no significant difference was
      observed in IgE levels between the severe and uncomplicated groups of patients
      with helminth infection, although IgE levels were significantly higher in
      helminth-infected patients than uninfected patients. These results suggest that
      IL-18 plays a key role in inducing severe malaria through another pathway, such
      as elevation of IFN-gamma, rather than its IgE inducing activity.

PMID- 14584383
TI  - Chloroquine, sulfadoxine-pyrimethamine and amodiaquine efficacy for the treatment
      of uncomplicated Plasmodium falciparum malaria in Upper Nile, south Sudan.
AB  - The current first-line and second-line drugs for Plasmodium falciparum malaria in
      South Sudan, chloroquine and sulfadoxine-pyrimethamine (SP), were evaluated and
      compared with amodiaquine, in an MSF-Holland-run clinic in eastern Upper Nile,
      South Sudan from June to December 2001. Patients with uncomplicated malaria and
      fever were stratified by age group and randomly allocated to one of 3 treatment
      regimes. A total of 342 patients was admitted and followed for 14 d after
      treatment. The dropout rate was 10.2%. Of those who completed the study, 104 were
      treated with chloroquine (25 mg/kg, 3 d), 102 with SP (25 mg/kg sulfadoxine and
      1.25 mg/kg pyrimethamine, single dose) and 101 with amodiaquine (25 mg/kg, 3 d).
      Adequate clinical response was observed in 88.5% of patients treated with
      chloroquine, 100% of patients treated with SP and 94.1% of patients treated with
      amodiaquine. In children aged < 5 years, the success rate was lower: 83.3% for
      chloroquine and 93.0% for amodiaquine. In adults no treatment failures were
      found, but children aged 5-15 years showed intermediate levels. In addition, we
      determined the initial genotypes of dhfr and dhps of 44 isolates from the SP
      treated group and > 80% were found to be wild type for dhfr and 100% for dhps.
      Two percent of isolates had a single mutation and 16% had double mutations of
      dhfr. These data are in full agreement with the clinical effectiveness of SP. A
      change in malaria treatment protocols for South Sudan is recommended.

PMID- 14584385
TI  - Density-dependent parasite establishment suggests infection-associated
      immunosuppression as an important mechanism for parasite density regulation in
      onchocerciasis.
AB  - The modulation of human immune response by filarial parasites has yielded
      contradictory experimental findings and attracted much controversy. We address
      the unresolved question of acquisition, establishment and accumulation of
      Onchocerca volvulus by using a modelling approach that relates computer
      simulations to cross-sectional data concerning parasite burdens in 913 West
      African onchocerciasis patients. It is shown that the acquisition of O. volvulus
      is not constant with host age; instead, the analysis of age profiles of parasite
      burdens strongly indicate the operation of immunosuppressive processes within the
      human host, associated with the presence of adult parasites or microfilariae. It
      is suggested that these processes suppress immunity against incoming infective
      larvae (L3), which themselves act as an immune modulating component once they
      have successfully overcome the barrier of concomitant immunity. Suppression of
      parasite-specific immunity leads to parasite establishment rates which increase
      along with the parasite burden, but which hardly depend on hyperendemic annual
      transmission potentials. Children, still immunocompetent due to low parasite
      burdens, acquire 0.1-0.5 adult female parasites per year, whereas older people,
      immunosuppressed due to high burdens, acquire 2-4 adult female parasites per
      year. Differences in parasite establishment between the forest and the savannah
      strains of O. volvulus are quantified and dynamic aspects of density-dependent
      parasite establishment discussed.

PMID- 14584386
TI  - Beri-beri: the major cause of infant mortality in Karen refugees.
AB  - During a prospective evaluation of malaria prophylaxis in pregnancy in a refugee
      population on the north-western border of Thailand from 1987 to 1990, an
      extremely high infant mortality rate (18%) was documented despite good access to
      health care. Infantile beri-beri was recognized as the main cause of death
      accounting for 40% of all infant mortality. Thereafter, severe vitamin B1
      deficiency in infants was diagnosed and treated promptly. The impact of this was
      assessed prospectively from 1993 to 1996 in a second cohort study. The case
      fatality of infantile beri-beri fell from almost 100% to 7%. The overall infant
      mortality rates declined from 183 to 78 per 1000 live births. Post-neonatal
      deaths fell by 79% (95% CI 65-87%) while neonatal mortality remained unchanged.
      Mortality resulting from acute respiratory infections did not change (15 and 11
      per 1000, respectively), whereas mortality attributable to beri-beri decreased
      from 73 to 5 per 1000 (P < 0.0001). Before its recognition approximately 7% of
      all infants in this population died from infantile beri-beri. This lethal but
      preventable syndrome may be more common than hitherto recognized, particularly in
      refugee populations, in this populous region.

PMID- 14584387
TI  - [Influence of smoking on longitudinal decline in one-second forced expiratory
      volume in clinically healthy Japanese men: a longitudinal study].
AB  - We prospectively studied 2140 clinically healthy men to assess the influence of
      smoking on longitudinal decline in one-second forced expiratory volume (FEV1.0).
      All the subjects had annual medical checks including pulmonary function tests
      from 1995 to 1999. The mean values +/- standard deviations of annual decreases in
      FEV1.0 (slope) were 22 +/- 49 mL/year in non-smokers, 26 +/- 52 mL/year in former
      smokers, and 33 +/- 57 mL/year in current smokers (p < 0.01; non-smokers vs.
      current smokers). The adjusted slope (slope divided by predicted value of FEV1.0,
      per year) in current smokers was also greater than that in non-smokers (p <
      0.01). Multiple regression analysis revealed that initial age, height, FEV1.0,
      and smoking status were significant parameters for determining the slope. This
      study clearly showed that smoking is an important risk factor foracceleration of
      the aging-related longitudinal decline in pulmonary function in Japanese men.

PMID- 14584388
TI  - [Clinical effects of long-term administration of pranlukast, a leukotriene
      receptor antagonist, on adult patients with bronchial asthma].
AB  - Eighty-one adult patients with bronchial asthma who suffered asthmatic episodes
      in spite of treatment with 400 mg/day of BDP were placed on pranlukast therapy
      for 4 weeks. Group I, which showed a 5% or greater increase in PEFR, continued
      oral pranlukast medication for an additional two years. Those patients who did
      not show an increase of 5% or greater in PEFR after 4 weeks of pranlukast therapy
      were instructed to continue the medication for another year. Group II, which
      exhibited a 5% or greater increase in PEFR after a one-year period continued
      medication for one more year. Medication was suspended for Group III, which
      failed to show improvement in PEFR after one year, and the group was placed under
      observation for the following year. Group I improved significantly in PEFR and
      exhibited a reduction in the frequency of b2 inhalation, the number of night
      visits to a medical facility, the amount of steroids inhaled, and the quantity of
      oral steroids given at regular intervals; and the Group I peripheral eosinophil
      count, serum ECP level, and FEV1.0 ameliorated. After one year, Group II also
      showed significant improvement in PEFR and a reduction in both the peripheral
      eosinophil count and the serum ECP level. This group's PEFR continued to improve
      after two years. One year after medication was suspended, Group III showed a
      significant increase in the number of night visits to a medical facility and a
      rise in the serum ECP level. These findings indicated the efficacy of pranlukast.

PMID- 14584389
TI  - [High efficacy of pleurodesis using OK-432 for controlling intractable
      pneumothorax associated with pulmonary lymphangioleiomyomatosis].
AB  - We evaluated the efficacy of pleurodesis using OK-432 (Picibanil) for the
      treatment of pneumothorax associated with pulmonary lymphangioleiomyomatosis
      (LAM). Seven episodes of pneumothorax in five patients with LAM were treated with
      pleurodesis using OK-432. First, all patients underwent tube thoracostomy
      drainage. After drainage, 5 or 10 KE of OK-432 was administered via the tube. If
      incomplete lung expansion or a continuous air leak occurred, an additional 5 KE
      of OK-432 was administered. Of the five patients, two developed pneumothorax for
      the first time and three had a history of previous pneumothorax. The mean total
      dose of OK-432 administered was 13.6 KE, and the mean period of tube drainage was
      11 days. The only recurrence of ipsilateral pneumothorax after OK-432 pleurodesis
      was observed seven years and eight months later in association with chronic
      respiratory failure in one patient. This patient was successfully treated with
      repeated pleurodesis using OK-432 during mechanical ventilation, and no
      recurrence has developed in the eight years since then. The main side effects of
      the procedure with OK-432 were fever and chest pain, which were well controlled
      by non-steroidal anti-inflammatory drugs. The study concluded that pleurodesis
      with OK-432 was an effective and safe treatment for intractable and recurrent
      pneumothorax associated with LAM.

PMID- 14584390
TI  - [A case of well-differentiated nonmucinous adenocarcinoma of the lung with an 18
      year clinical course before surgery].
AB  - A 56-year-old woman was referred for an abnormally dense area in the right upper
      lung field detected at medical checkup. This shadow had been pointed out
      frequently since she was 38 years old, but no pathological diagnosis of lung
      cancer had been given. The size of the abnormal area had gradually increased over
      the 18 years. Since lung cancer was suspected on the basis of the radiographic
      findings, she underwent open lung biopsy. Pathologically, the tumor tissue showed
      a lepidic growth pattern on the wall of preexisting alveoli; and formation of
      fibrotic foci caused by the collapse of alveoli and the microscopic destruction
      of the elastic fiber framework were seen in the tumor. There was no vascular
      invasion or lymphatic infiltration in the tumor. It was diagnosed as well
      differentiated nonmucinous adenocarcinoma, p-T2 N0 M0. Although this tumor was
      untreated for 18 years from the first detection using chest radiography, the
      critical invasive features were not in evidence pathologically.

PMID- 14584391
TI  - [A case of bacteria-associated hemophagocytic syndrome induced by nosocomial
      pneumonia].
AB  - This study reviews the case of a 67-year-old man who initially presented with
      high fever and dyspnea. He was subsequently admitted for treatment of pneumonia.
      On admission, severe leucopenia and thrombopenia were observed in the peripheral
      blood, with significant phagocytosis of hematopoietic cells including
      erythroblasts and leukocytes by macrophages in the bone marrow. Following the
      administration of antibiotic therapy, an improvement in pneumonia and cytopenia
      symptoms was noted. Clinically, we diagnosed this case as bacteria-associated
      hemophagocytic syndrome (BAHS) with community-acquired pneumonia. In general BAHS
      is seen following severe hematologic disease or pneumonia, and so the treatment
      of BAHS is quite difficult. This particular case had no additional hematologic
      disorder, and all presenting symptoms of BAHS were resolved immediately following
      the improvement in pneumonia with post-antibiotic therapy.

PMID- 14584392
TI  - [A case of amylase-producing lung cancer].
AB  - A 72-year-old man was admitted to our hospital because of progressive dyspnea due
      to pulmonary emphysema. Chest CT revealed a nodular lesion in the right S6 and
      swollen right hilar lymph nodes. The diagnosis was not confirmed
      bronchoscopically. A subsequent biopsy of a subcutaneous mass in the left lateral
      pectoral region demonstrated metastatic cancer. Laboratory data on admission
      showed marked elevation of amylase activity in both serum and urine. Amylase
      isozyme patterns identified the salivary types. The pancreas and salivary glands
      were unlikely to have any clinical involvement in the hyperamylasemia, but lung
      cancer with subcutaneous metastasis was strongly suspected clinically as the
      source. Chemotherapy failed to prevent tumor progression and the patient
      eventually died of respiratory failure. Immunohistological examination of the
      subcutaneous lesion showed positive staining for salivary-type amylase, whereas
      that of the lung primary lesion disclosed small cell carcinoma and negative
      staining for amylase. In most cases, amylase-producing lung cancers have been
      diagnosed as adenocarcinoma. Amylase-producing small cell carcinoma is very rare.

PMID- 14584393
TI  - [A case of eosinophilic lung disease presenting asthma-like symptoms and
      centrilobular shadows in both lung fields].
AB  - This case, in a 23-year-old man presenting with cough, sputum, dyspnea on effort
      and wheezing, had been diagnosed as bronchial asthma at another hospital. Because
      inhaled steroid and theophylline were far from effective, he was admitted to our
      hospital for further evaluation. A blood test revealed marked eosinophilia. Chest
      radiography showed diffuse, small nodular shadows in both lung fields, and a
      chest CT scan demonstrated diffuse centrilobular nodules and thickening of the
      bronchi and bronchioles. A spirometric test showed obstructive and restrictive
      ventilatory impairment, but the depressed forced vital capacity failed to show
      improvement in response to bronchodilator inhalation, discouraging a diagnosis of
      asthma. Eosinophilic lung disease with prominent eosinophilic bronchiolitis was
      diagnosed on the basis of BAL eosinophilia and thoracoscopic lung biopsy
      findings. The symptoms and blood eosinophilia were responsive to administration
      of oral prednisolone (30 mg daily); radiographic and CT findings also showed
      improvement. This case showed a marked similarity to the recently reported
      "eosinophilic bronchiolitis", and was probably not a type of bronchial asthma.

PMID- 14584395
TI  - [Two cases of prostate cancer found primarily from lung metastatic lesions].
AB  - We report two cases of prostate cancer found primarily from a metastatic lesion
      appearing in a chest radiograph. Patient 1 was admitted to our hospital because
      his chest radiograph and chest CT showed pleural effusion on the left.
      Thoracocentesis and pleural biopsy were unremarkable, so he was observed as both
      an outpatient and an inpatient. His general condition worsened, and after the
      third admission, he died. His autopsy revealed prostate cancer and positive
      immunohistochemical reactions for PSA and PSAP in both lungs, and prostate
      specimens demonstrated that prostate cancer had metastasized to the lung. Patient
      2 was referred for evaluation of a bilateral multiple nodular shadow in a chest
      radiograph, and prostate cancer was discovered. Immunohistochemical reactions for
      PSA and PSAP were positive in both specimens of TBLB and prostate biopsy,
      confirming that the multiple lung tumors were metastases from prostate cancer.

PMID- 14584394
TI  - [An autopsy case of pseudomesotheliomatous adenocarcinoma of the lung complicated
      with brain stem infarction due to nonbacterial thrombotic endocarditis].
AB  - A 53-year-old man was admitted to our hospital for back, left shoulder and upper
      limb pain. Chest radiography and CT on admission revealed right pleural effusion
      and a focal plate-like thickening of the major fissure. Pleural effusion cytology
      revealed adenocarcinoma, which was diagnosed as non-small-cell lung cancer with
      bone metastasis. The patient suffered from DIC, melena and multiple cerebral
      infarctions during chemotherapy and died on the eighth day of the second course
      of chemotherapy. Autopsy revealed a pseudomesotheliomatous adenocarcinoma
      covering the pleura of the right middle lobe, systemic thromboembolism and
      vegetations on the aortic valves due to nonbacterial endocarditis.
      Pseudomesotheliomatous adenocarcinoma of the lung, a rare form of lung cancer,
      complicated with DIC and nonbacterial endocarditis, is reported.

PMID- 14584396
TI  - [Two cases of interstitial pneumonia with anti-Jo-1 antibodies in the absence of
      myositis].
AB  - We present two cases of interstitial pneumonia with anti-Jo-1 antibodies in the
      absence of myositis. The first patient was a 38-year-old woman and the second, a
      59-year-old woman. Both patients were admitted to our hospital complaining of dry
      cough and dyspnea on effort. The diagnosis of interstitial pneumonia was made
      from chest radiography, computed tomography and surgical lung biopsy. Anti-Jo-1
      antibodies, which were highly specific for polymyositis and dermatomyositis
      (PM/DM), were detected in both patients. However, the serum creatine kinase
      concentrations and electromyographic findings in both patients were normal, and
      no clinical signs (including muscle weakness, rash and arthralgia) were found. In
      the first patient, oral prednisolone (PSL) treatment (20 mg day) improved the
      interstitial pneumonia, but PSL has now been tapered to 17.5 mg day. In the
      second patient, oral PSL treatment (40 mg day) improved interstitial pneumonia,
      and the dose was tapered to 5 mg day. The second patient was followed for more
      than 10 years after treatment, but she has never shown any signs of clinical
      myositis. Further investigation will be required, because no pathophysiological
      relation between anti-Jo-1 antibodies and interstitial pneumonia with PM DM has
      yet been established.

PMID- 14584397
TI  - [A case of bird fanciers' lung with endobronchial polyps].
AB  - A 34-year-old woman who had been keeping five budgerigars in her home was
      admitted with cough and progressive exertional dyspnea that had continued for
      three months. Chest CT scan demonstrated diffuse centrilobular nodular opacities
      throughout both lung fields. Flexible bronchoscopy revealed polypoid lesions with
      diameters of 2-3 mm located at the right B1/B2 spur. B3a/B3b spur and
      middle/lower bronchus spur. Their surfaces were glossy and smooth but slightly
      lobulated. The histological findings were consistent with inflammatory polyps
      containing lymphoid follicles in a dense infiltrate of lymphocytes. A positive
      environmental provocation test and precipitating antibodies confirmed the
      diagnosis of hypersensitivity pneumonitis (HP) caused by budgerigars (bird
      fanciers' lung). To our knowledge, there is no previous report of HP accompanied
      with endobronchial polyps, but this rare case shows the involvement of large
      airways in HP.

PMID- 14584398
TI  - [A giant pulmonary aspergilloma managed surgically in an elderly man].
AB  - We describe a case of giant pulmonary aspergilloma in a 79-year old man. He had
      undergone an operation for pulmonary tuberculosis of the right lung at the age of
      49 years. His chest ragiograph showed a large fungus ball in the right upper lung
      field. Taking his age and pulmonary condition into consideration, we performed a
      cavernostomy and fungus ball resection to prevent life-threatening hemoptysis.
      The postoperative course was satisfactory and without complication. Cavernostomy
      may be an alternative choice in high-risk aspergilloma patients.

PMID- 14584399
TI  - [Cyclosporin improved pure red cell aplasia associated with thymoma and tended to
      decrease thymoma size: a case report].
AB  - The case was a 56-year-old man who underwent extended thymothymectomy in 1993
      because of an invasive thymoma classified as Masaoka IIa. The tumor was
      disseminated through the right thoracic cavity in 1994. Although the chemotherapy
      was repeated, the disseminated thymoma tended to increase in size. The patient
      was suffering from severe anemia, and pure red cell aplasia was diagnosed in
      September 2002. The administration of cyclosporin was initiated, and not only
      brought about improvement of pure red cell aplasia but also tended to shrink the
      thymoma. Cyclosporin may be an effective drug for the reduction of thymoma as
      well as for pure red cell aplasia.

PMID- 14584400
TI  - [A case of combined hypersensitivity pneumonitis and bronchial asthma due to
      isocyanate (MDI)].
AB  - A 29-year-old man was admitted to our hospital complaining of cough, wheezing,
      dyspnea, and fever one month after handling paint spray containing isocyanate
      (MDI). Chest HRCT findings showed diffuse ground-glass attenuation in both lung
      fields. A pulmonary function test revealed restrictive impairment, and the
      reversibility test was positive. His symptoms, HRCT findings, and pulmonary
      dysfunction were improved only after the cessation of isocyanate administration.
      BALF showed lymphocytosis, and the pathological findings of the TBLB specimen
      revealed cellular alveolitis, but no Masson bodies or epitheloid cell granuloma.
      As a result of environmental provocation, fever, hypoxia, and reduced peak
      expiratory flow developed, and the environmental provocation test was positive.
      The specific antibodies against MDI and TDI were positive in both serum and BALF,
      and the lymphocyte stimulation test against MDI was positive in peripheral blood.
      Combined hypersensitivity pneumonitis and bronchial asthma due to isocyanate were
      therefore diagnosed. Pulmonary dysfunctions due to isocyanate are known to
      include bronchitis, bronchial asthma, and hypersensitivity pneumonitis. However,
      case reports of combined hypersensitivity pneumonitis and bronchial asthma due to
      isocyanate are rare.

PMID- 14584401
TI  - [A case of schwannoma of the chest wall showing a bead-like appearance in MRI].
AB  - A 31-year-old man was referred to our hospital because of a chest X-ray
      abnormality. Computed tomography showed an extra-pulmonary mass along the left
      8th rib. T1-weighed magnetic resonance imaging (MRI) revealed a mass lesion with
      intermediate signal intensity. T2-weighed MRI showed a high signal intensity in
      peripheral and multiple central portions with intermediate signal intensity,
      which yielded a bead-like appearance. Gadopentetate dimeglumine-enhanced T1
      weighted MRI showed marked contrast enhancement in the central zone of the mass.
      En bloc resection of the mass with the left 8th rib was performed. The tumor
      resembled a rosary in gross appearance, and histological examination confirmed
      the diagnosis of a benign schwannoma arising from the intercostal nerve. The bead
      like appearance in the MRI was unique and had never been reported before for such
      a tumor. The postoperative course was uneventful, and the patient has been well
      for eighteen months.

PMID- 14584402
TI  - Forteo (teriparatide): first approved medication to rebuild bone.

PMID- 14584403
TI  - Case report: detection of an advanced ovarian malignancy by cervical cytology.
AB  - There are currently no recommended screening tests for the early detection of
      ovarian cancer. Ovarian malignancies are most often discovered on bimanual exam
      at advanced stages, resulting in a high mortality from this disease. While the
      Papanicolaou (Pap) smear is not a reliable screen for the detection of ovarian
      cancer, abnormal cytology may be the initial indicator of ovarian malignancy.
      This is a case report of an invasive serous adenocarcinoma of the ovary that was
      discovered as the result of a clinical work-up for abnormal cytology reported on
      a Pap smear.

PMID- 14584404
TI  - [Management and organisation of research in forensic medicine].

PMID- 14584405
TI  - [Problem-oriented analysis of the medical-anthropologic identification in
      forensic medicine].
AB  - The paper deals with a detailed analysis of the key trends in the current
      forensic-medical anthropology. The attention is focused on diagnosis of group
      personality signs: presence of osseous substance, species diagnosis, attribution
      of remains to one or several cadavers, determination of a possible residence
      territory, group adherence of the osseous and tooth tissues, as well as
      determination of race, sex, age, stature, etc. Such topical issues as personality
      reconstruction by skull, establishment of kindred, and special identification
      tools are detailed. Finally, conditions affecting the objects of expertise, i.e.
      prescription of corpse burying, fragmentation, signs of cadaver extermination,
      are also elucidated.

PMID- 14584406
TI  - [Role of the forensic medical expertise in the campaign of Russia Defense
      Ministry against trafficking of narcotics and strong drug substances].
AB  - The forensic medical measures undertaken by Russia's Defense Ministry (RDM) in
      its campaign against trafficking of narcotics and drastic medicines in Russia's
      territory are addressed in the paper. The dynamic mortality rate due to poisoning
      by narcotic and psychotropic agents (among Russian citizens) is shown for 1996
      2001; the following issues are also discussed: specificity of drug-trafficking
      and drug-addiction in the contemporary Russian society and, primarily, in the
      Armed Forces of the Russian Federation and the conditions, on which the RDM
      expert forensic-and-medical institutions are involved in state measures against
      trafficking of narcotics and drastic medicines in Russia's territory.

PMID- 14584407
TI  - [Changes in adrenergic and cholinergic innervation of the external genitalia in
      alcohol and drug intoxication].
AB  - Eighteen cadavers of persons, who died of acute and chronic alcohol and drug
      intoxication (ephedron-addiction), were used to study the changes in the spinal
      nerve plexuses and external genitals. The activity of acetylcholinesterase and of
      NADPH-diaphorase was determined histochemically; the adrenergic nerve fibers were
      detected by a glyoxyl-acid technique. Rectified changes in the relative density
      of adrenal-cholinergic- and nitroxydergic structures and in the activity of
      mediators in different intoxications were found. The chronic intoxication by
      alcohol and ephedron was accompanied by a reduced activity of enzymes involved in
      the metabolism of acetylcholine, nitric oxide and catecholamines. A lower density
      was observed in the nerve fibers that contained the examined substances. The
      results can be used as an additional criterion in evaluating the male sexual
      function status.

PMID- 14584408
TI  - [Postmortem detection of hemp intoxication].
AB  - The diagnostic tools applicable to the forensic medical expertise of cadavers in
      cannabinoid intoxication (CI) were evaluated. Histochemistry with incubation of
      stable blue "B" (SBB) were used for the detection of cannabinoids in the bronchi
      and lungs. Hyperemia and capillarostasis in the mucous tunics of the mouth and
      stomach as well as hyperemia and edema in the lungs and brain were
      histochemically detected in CI. The histochemical activity of aldehyde
      dehydrogenase (AlDG) was most essentially decreasing in the adrenal glands and
      brain of younger persons. The SBB reaction in the bronchial and alveolar
      epithelia was positive in 85% of cases. A high proof value of the CI diagnostics
      was pointed out in cadaver expertise.

PMID- 14584409
TI  - [Evaluation of disorders in the liquor circulation in craniocerebral trauma].
AB  - The modern methods of complex examinations of the brain in craniocerebral trauma
      are addressed and the possibilities of the topographic-and-anatomic
      substantiation in the forensic-medical (expert) evaluation of traumatic lesions
      of liquor-circulation structural elements are elucidated in the paper.
      Morphometry data characterizing the dislocation manifestations are presented with
      respect to the dislocation intensity and severity.

PMID- 14584410
TI  - [X-ray changes in the region of long-bone fractures in early post-traumatic
      period].
AB  - Described are the results of computer-based X-ray interpretation of images of
      long-bone fractures made immediately after trauma. The difference between
      roentgenograms made on the day of trauma and on the next day is demonstrated. A
      new soft, which was used by the author for X-ray interpretations, is depicted.

PMID- 14584411
TI  - [The specificity of gunshot wounds caused by rubber buck shot].
AB  - Described in the paper are forensic-medical cases related with examinations of
      wounds inflicted by rubber case-shot--a relatively rare ammunition. The
      morphology of the above wounds and specific features of deposition of "shot
      metals" in the damaged region were studied. The possibilities of fixing a shot
      distance and ammunition type were defined.

PMID- 14584412
TI  - [The ordinal localization of mono-type foot bones].
AB  - The osteologic collection of the chair for anthropology, Moscow State University,
      comprising male (n = 70) and female (n = 14) foot bones from persons aged more
      than 18-20, was investigated. An appropriate Martin program was fixed to the
      instep bones (IB) of the proximal and middle toe phalanxes (4 sizes for each
      bone) with 65 signs being studied in each case. The mathematical data processing
      was SPSS-aided. Diagnostic models for defining the order IB localization in the
      proximal and middle phalanxes were elaborated on the basis of discriminative
      analysis. The classification accuracy is maximal for IB (80-100%) and minimal for
      the middle phalanxes (26.19-77.38%). The definition of the order localization of
      phalanxes in toes 2-5 is virtually impossible. The designed method can be used
      alongside with the routine anatomic-and-morphological findings. The congruence of
      surfaces in the instep-phalanx and interphalangeal joints must be necessarily
      checked.

PMID- 14584413
TI  - [Results of applying molecular-and-genetic markers of chromosomal DNA in
      identification of unrecognizable remains of servicemen lost in military actions
      in the Northern Caucasus].
AB  - The results of applying molecular-and-genetic markers of chromosomal DNA in
      identifying unrecognizable remains of servicemen lost as dead in 1994-1996 and
      1999-2001 military campaigns in the Northern Caucuses are summarized in the
      paper. Some of the specific features related with enzymatic amplification typing
      of DNA preparations sampled from degraded biological tissues of strongly deformed
      or decayed cadavers were analyzed. The typing results were analyzed by the AB0
      system of degraded expertise samples in order to check the reliability of routine
      forensic-biological examinations as applicable to cadaver tissues with pronounced
      putrefactive changes. It was established that group-specific antigens of the AB0
      system were correctly determined only in 67.5% of cases. False results were
      obtained in the other 32.5% of cases. Most of them were related with
      determination of groups 0(I) and A(II).

PMID- 14584414
TI  - [Legal regulation and management of fee for services in the state expert
      institutions].
AB  - With due regard for the economic situation in regions, differences in the
      material-technical and personnel provision of each forensic-medical bureau (FMB),
      paying capacity of local residents and for other factors, a method for estimating
      the cost of forensic medical services was elaborated and offered for use. The
      formula of cost estimation for rendered services allow for basic wages (BW) and
      bonuses, sick-list and vacation payments, overhead charges (including FMB wear
      and-tear), and BW assignment to off-budget funds (which constitute, in total, the
      self-cost of services) as well as the planned profit and road taxes.

PMID- 14584416
TI  - [Yakov Lvovich Leibovich--a prominent figure in Russian forensic medicine].

PMID- 14584415
TI  - [The forensic medical significance of cis-AB group in the AB0 system and its
      diagnostics in the traces of human discharges].

PMID- 14584418
TI  - [Electrocardiography].

PMID- 14584417
TI  - [Failure of antiarrhythmia agents and understanding the phenomenon of
      proarrhythmia].
AB  - The end of 80ies and the beginning of 90ies in arrhythmology was characterized by
      the demonstration of so called proarrhythmia, when drugs, particularly
      antiarrhythmic ones, induced serious, frequently fatal arrhythmias. The resulting
      pharmacotherapeutic skepsis in the treatment of, in particular, ventricular
      arrhythmias were accompanied at the same time by a powerful development of non
      pharmacological modes of treatment of arrhythmias, especially by implantable
      defibrillators. The causes of proarrhythmia were identified with the evolution of
      knowledge in the genetic basis of hereditary syndrome of long QT interval. The
      first mutation was identified in 1991 and other mutations in the four subsequent
      years. The mutated genes controlling the synthesis of ionic membrane channels
      cause disorders in the repolarization phase of action potential. Their expression
      in individual types of myocytes is not homogenous, most affected being the M
      cells of ventricular myocardium. It results in a dispersion of repolarization
      which, together with induction of early after depolarization, causes the origin
      of polymorphic ventricular tachycardia--TdP. In the 90ies of 20th century there
      were increasingly frequent reports on sudden arrhythmic death in patients, who
      had been treated with non-cardiac drugs. They were caused by polymorphic
      ventricular tachycardia associated with the long QT interval. The syndrome was
      named as acquired syndrome of long QT interval, based on the drug-induced delayed
      repolarization of myocyte. The slowing-down is caused by affected membrane
      channels known from the syndrome of hereditary LQTS. The very low frequency of
      these fatal complications has been explained either by an obscure genetic defect
      or a disorder in metabolism of the therapeutic drug, but especially due to drug
      interactions metabolized in a similar way and similarly influencing the function
      of membrane channels. Sixty drug molecules with proarrhythmic potential have been
      identified so far, but the list is probably not complete yet.

PMID- 14584419
TI  - [New techniques in recording cardiac electric potentials].
AB  - New technologies of recording and processing of electrical cardiac potentials
      made significant advances in the course of recent years, contributing to the
      production of instrumentation the application of which enables a high level of
      diagnostics, therapy and rehabilitation to be reached in internal medicine.
      Modern technology of recording potentials by means of vacuum electrodes with
      surface finish and simultaneous application of new adaptable filters enable a
      more accurate digital processing of electrical pulses and a higher quality of
      their recording, indication, transmission, interpretation and archiving. The
      given requirements are complied with especially by new polyfunctional
      instruments, made e.g. by the firm SCHILLER AG, and some specialized devices of
      other producers, serving, among others, for examination of heart rate and its
      variability. New technical devices, applied sensibly and economically, should be
      accessible in the near future also to peripheral cardiologic and internal
      centres.

PMID- 14584420
TI  - [Pitfalls in the interpretation of electrocardiographic signals].

PMID- 14584421
TI  - [The ECG--a basic examination method in the cardiology laboratory].
AB  - Electrocardiography entertains a centennial anniversary, but it still remains the
      basic and widely used examination method in heart diseases. Its important
      position remains even within the framework of basic clinical research, where it
      represents a starting parameter for the evaluation of other more sophisticated
      methods of examination. The strengthening of basic research and rapid application
      of the obtained knowledge in clinical practice were the main reasons for the
      foundation of the "Laboratory for Research of Blood Circulation Control". The
      laboratory is particularly engaged in investigating the influence of autonomous
      nervous system (ANS) in pathophysiology, diagnostics and therapy of
      cardiovascular diseases. ANS plays an important role in the regulation of blood
      pressure. It has been already sufficiently proved that disorders in ANS function,
      especially a superfluous increase in the sympathicus activity, significantly
      participates in the origin and progression of many serious cardiovascular
      diseases. In spite of the fact that the sympathicus function has been explored
      relatively in detail, there is still markedly less information on the
      parasympathicus function. The research in the sympathicus function has been made
      possible particularly due to the evolution of microneurography. This method makes
      it possible to directly evaluate the frequency and intensity of nervous impulses,
      discharge from the brain to the vessels of skeletal muscles. There is still no
      similar available method for the investigation of parasympathicus. The authors
      therefore presently investigate a direct short-term and long-term influence of
      parasympathicus in the blood pressure control by means of implantable vagus
      stimulator.

PMID- 14584422
TI  - [Electrocardiography in acute myocardial infarct].

PMID- 14584423
TI  - [Electrocardiography in cardiomyopathies].
AB  - ECG plays a predominantly screening role in cardiomyopathies. It is particularly
      important in hypertrophic cardiomyopathies, where atrial abnormities may be
      present (25%), positive voltage criteria in hypertrophy of the left ventricle
      (63%), pathological Q or QS wave (24%), missing septal q in V5 and V6 (49%),
      missing increase in the R wave in V1-V3 (29%) and high R waves in V2-V3 (15%),
      changes in repolarization phase of the ST-T segment (87%). The left Tawar arm
      blockade is particularly typical for dilatation cardiomyopathies. In
      arrhythmogenic cardiomyopathies of the right ventricle the epsilon ware can be
      found as well as negative T waves in the leads from the right precordium and
      ventricular arrhythmias in the shape of the left Tawar arm blockade.

PMID- 14584424
TI  - [Changes in the ECG in chronic heart failure and after transplantation].
AB  - ECG examination belongs to basic procedures in the care of patients with heart
      failure. The Euroheart Survey study followed the data and therapy of hospitalized
      patients with chronic heart failure (CHF) with participation of 116 hospitals
      from 25 European countries and surveyed documentation of 45,993 patients
      dismissed from internal wards. A new atrial fibrillation or supraventricular
      tachycardia affected 25.3% of patients, chronic fibrillation was encountered in
      23%. Bradyarrhythmia occurred in 10.8% and pacemaker was applied in 8.5% of
      patients. Ventricular arrhythmias were present in 8.4%, implantable cardiovertor
      defibrillator in 1.5%. Syncope was reported in 15% and the arrhythmic death was
      described in 1.83%. The patients with heart failure suffer from a high incidence
      of ventricular arrhythmias. About 40-50% of death events in patients with CHF are
      estimated to be associated with a sudden death or arrhythmia. Large clinical
      studies investigate the occurrence of and influence upon the sudden death as
      indices of therapy. The disorders of rhythm as well defects of ventricular
      conduction may be the risk factors of survival in patients with CHF. The Italian
      registry of heart failure includes examinations of 5 517 patients. A complete
      blockade of the left bundle branch block (LBBB) was present in 25.2% patients,
      whereas a complete blockade of the right bundle branch block (RBBB) occurred in
      6.1%. The patients differed in the CHF cause: the group with LBBB suffered more
      frequently from dilatative cardiomyopathy, whereas IHD more present more
      frequently in patients without the blockade. The groups also differed in the
      severity of the disease. The patients with LBBB had a higher prevalence of heart
      weakness NYHA III and IV (32.8% and 26.4%, respectively, P < 0.001), lower
      systolic blood pressure, more frequently third heart sound (34.2% versus 22.2%, P
      < 0.001), cardiomegaly classified as a cardiothoracic index higher that 0.55
      (63.2% versus 55%, P < 0.04). In the course of one-year observation 11.9% of
      patients died, death being evaluated as sudden in 46%. The one-year mortality in
      patients those with LBBB was 16.1% in contrast to 10.5% in those who had not
      suffered from the blockade. A sudden death affected 5.5% of patients in the whole
      cohort, the frequency being again in LBBB (7.3% vs. 4.9%). The risk further
      increased with a simultaneous atrial fibrillation. After heart transplantation,
      ECG is also of importance for revealing an acute rejection. In the bilateral
      operation technique a direct alteration of the sinus node could be the cause of
      dysfunction. Various bradyarrhythmias developed in later periods of time. A
      modification of the operation technique has been used in the last 10 years. The
      application of bicaval method eliminated brachycardiac complications after heart
      transplantation. A cardiostimulator proved to be necessary in 5 to 15% of
      patients when biatrial technique was used, whereas it was virtually not required
      with the bicaval technique. The blockade the left bundle branch block is an
      unfavorable prognostic factor in the same way as in CHF, whereas of the right
      bundle branch block is critical in the heart transplantation. It is supposed to
      be caused by surgical or thermal damage or it is also associated with different
      degree of the right ventricular dysfunction and a higher number of rejections.
      The blockade is also associated with worse one-year survival (74% vs. 92%, P <
      0.03). CONCLUSION: ECG retains its position even in modern times not only in the
      diagnosis of conditions responsible for heart failure, in the diagnosis of
      disorder of rhythm and conduction, but it is also of prognostic value. It also
      retains its position in the same areas as in heart failure, i.e. in the diagnosis
      and prognosis in heart transplantation.

PMID- 14584425
TI  - [Biventricular cardiac pacing].
AB  - Chronic heart failure (CHF) is a very frequent condition. Its frequency increases
      with prolongation of median life expectancy and due to improvements in medical
      care. However, medical treatment does not allow adequate control of symptoms in
      many cases. Therefore, various nonpharmacological approaches are being developed.
      The so-called biventricular pacing is one of them. Its main goal is to restore
      impaired mechanical cardiac synchrony that is present in patients with prolonged
      QRS duration due to inter- or intraventricular conduction abnormality. At
      present, biventricular pacing can be achieved through positioning of a special
      pacing lead into a branch of the coronary sinus on the surface of the left
      ventricle and implanting the other lead into the right ventricular cavity, and
      the third lead into right atrial appendage. Clinical trials and experience from
      many centres have documented improvements in clinical status in the vast majority
      of patients. An improvement in functional classification (NYHA) by at least one
      class, prolongation of the six minute walk distance by 20-40%, increase the
      maximal oxygen uptake by 10-40% a beneficial effect on quality of life can be
      expected. Preliminary results of the COMPANION trial have suggested that cardiac
      resynchronization therapy is associated with prognostic effect, especially in
      conjunction with implantable cardioverter-defibrillator.

PMID- 14584426
TI  - [Intracardiac electrocardiography in the diagnosis and therapy of arrhythmia].
AB  - The recording of intracardial electrocardiograms (IECG) has made good progress in
      the arrhythmology during last 15 years. First the aim was to describe the
      characteristics of the conduction system of the heart (Hisogram recording),
      followed by the evaluation of pathologies of the conduction system (meaning
      bradyarrhythmias), electrical activation of the myocardium when tachyarrhythmia
      is ongoing for diagnosis and punctual localization of accessory pathways during
      endocardial mapping. The next logical step as a reaction to the knowledge of
      endocardial mapping was the evaluation of new therapeutic methods--DC followed by
      radiofrequency ablations--nonpharmacological therapeutic antiarrhythmic
      procedures, usually used in electrophysiology labs of cardiological departments.
      Nowadays pacemakers are equipped with possibilities of intracardial atrial and
      ventricular signal recording which enables the use of accesorial antiarrhythmic
      functions. Intracardial electrocardiogram recording plays the dominant role in
      implantable cardioverter-defibrillators, where the main part of algorithms for
      detection and discrimination is based on the electrocardiograms. From both the
      diagnostic and therapeutic points of view intracardial signal recording is
      playing an important part in clinical practice in arrhythmology these days.

PMID- 14584427
TI  - [Atrial fibrillation].
AB  - Atrial fibrilation is the most frequent arrhythmia, the occurrence increasing
      with age and associated diseases. The incidence at the age below 60 years is
      markedly lower than one per cent, whereas in persons above 80 years of age it
      exceeds six per cent. The occurrence in patients with heart failure is from 10%
      (NYHA II) up to 50% (NYHA IV). Atrial fibrillation is classified into that
      observed for the first time and permanent, respectively, while transient forms
      include paroxyzmal and persistent atrial fibrillation. The diagnosis is based on
      ECG recording, while echocardiography is most significant. The therapy includes
      two basic questions--anticoagulant or anti-aggregation treatment and the control
      of rhythm or frequency. The anticoagulant therapy should be introduced in all
      patients, where contraindications are not present, being necessary before every
      cardioversion, provided atrial fibrillation lasts more than two days. In patients
      without any heart disease and with a physiological echocardiogram it is possible
      to administer only anti-aggregation treatment. Cardioversion (the control of
      rhythm) is recommended to all symptomatic patients, in other cases and especially
      in older persons the control of frequency is safer and of more advantage.
      Electrical cardioversion is more effective that a pharmacological treatment, the
      sinus rhythm is preferably controlled by dofetilid, ibutilid, propafenon and
      amiodaron. For the control of heart rate beta-blockers, diltiazem, verapamil and
      digitalis are recommended.

PMID- 14584428
TI  - [Treatment of ventricular arrhythmias].
AB  - The term ventricular arrhythmia denotes various disorder in the cardiac rhythm-
      from isolated monomorphic ventricular extrasystoles to ventricular flutter and
      fibrillation. The choice of therapy of ventricular arrhythmias is primarily based
      on prognostic aspects. Ventricular tachycardias represent the main cause of
      sudden cardiac death, which is responsible for more than 60% of all deaths for
      cardial causes. In the industrially advanced countries the ventricular
      tachyarrhythmias represent more than 90% of cases based on coronary disease. The
      prevention of sudden death is directed particularly to prevention and therapy of
      ischaemic heart disease. The prognostic classification divides ventricular
      tachycardias into benign, potentially malignant and malignant ones, respectively.
      The benign arrhythmias do not require therapy. In the malignant (i.e. potentially
      lethal) ventricular tachyarrhythmias the implantation of cardioverter
      defibrillator represents the most efficient treatment. In the largest group of
      patients with potentially malignant ventricular arrhythmias the present risk
      oriented stratification enables a partial identification of persons with markedly
      increased risk of sudden death. They may be considered for preventive
      implantation of cardioverter-defibrillator. In some patients the therapeutic
      effect is reached by application of various therapeutic methods including a
      combination of pharmacological and non-pharmacological therapy, which also
      includes catheterization or surgical ablation of the arrhythmogenic substrate. A
      corresponding attention should be devoted to the basal cardial disease.

PMID- 14584429
TI  - [Cardiac bradyarrhythmia ].
AB  - Permanent cardiac pacing was introduced in 1958 and till the end of 70s this
      method saved lives in particular of the patients with advanced atrioventricular
      block. The implantation technique has changed from complicated thoracotomy to
      endovasal approaches. The introduction of physiological AV sequenced
      atrioventricular pacing marked a significant progress in this field. Acute
      haemodynamic studies documented positive effect of the atrial contribution.
      Numerous studies subsequently analyzed the influence of different pacing regimes
      on total and specific cardiovascular mortality and morbidity. It can be concluded
      that on the basis of present evidence-based medicine the use of physiological
      pacing is clearly indicated in the patients with expressed sinus bradycardia and
      AV block of a higher degree. Atrial pacing remains an ideal solution for the
      patients with isolated sinus node dysfunction and sufficient atrioventricular
      conduction capacity. Research is continued in order to clarify how to influence
      the occurrence of ventricular fibrillation by permanent cardiac pacing including
      the use of preventive algorithms. This topic has not yet been reliably and
      unambiguously concluded. Biventricular pacing is currently established and
      recognized not only for typical indications in cases of bradyarrhythmias but also
      to solve primary haemodynamic problems in the patients with advanced heart
      failure and evidence of ventricular dyssynchrony.

PMID- 14584430
TI  - [Molecular genetic aspects of arrhythmias].
AB  - The sequencing of human genome was completed in 2001. The position of particular
      DNA base is established-i.e. we know all "letters" in the "book" but we
      understand only limited number of "words" i. e. only limited number of genes was
      identified. And the human genome consists of about 30,000 genes from which
      through the mechanism of alternative RNA splicing more than 100,000 genes can be
      derived. All the genes of one individual form the genotype. The expression of
      genotype in particular environment forms the phenotype. What is not present in
      genotype can neither be present in phenotype. In the last decade a substantial
      progress was achieved in understanding of membrane processes mostly due to
      research of relatively rare inherited monogenous arrhythmic syndromes--first of
      all the long QT syndrome. It is caused by mutations in ion channel genes and it
      provides a model of arrhythmogenesis on molecular level. Ventricular arrhythmias
      are important cause of mortality in patients with cardiovascular diseases. New
      studies have provided strong evidence for familial sudden cardiac death (SCD)
      aggregation and therefore also genetic influence. Parental history of SCD
      increases the relative risk of SCD for offspring to 1.8. In the case of both
      maternal and paternal SCD events the risk for offspring is a remarkable 9.4.
      There are 3 pathways by which genetic variation may contribute to risk for SCD:
      1. alterations in electrogenesis and conduction, 2. formation and stability of
      atherosclerotic plaque, thrombogenesis and ischemia within the coronary
      circulation, 3. control of myocardial excitability and vascular motorics. The
      main objective of both today and future research is identification of inheritable
      "molecular" risk factors of arrhythmias. Understanding of this level of
      pathophysiological processes will subsequently lead to new generation of both
      diagnostic and therapeutic methods.

PMID- 14584431
TI  - [Methods in stress ECG].
AB  - In spite of the continuous development of methods of examination, the exercise
      ECG still retains its position in the palette of examination methods for
      ischaemic heart disease. The examination mostly employs a mechanical load on
      bicycle ergometer or a treadmill. In the changes in the ST segment (horizontal or
      descending regression of ST surpassing 1 mm, i.e. 0.1 mV, measured 60-80 ms from
      junction) is still considered as the most indicative ECG index. The detection
      rate of ischaemic changes is proportional to the number of used leads.
      Sensitivity of visually evaluated exercise ECG is in the rang of 54 to 66%,
      specificity is around 82%. The elevation of ST-segment in aVR and V1 leads during
      exercise is considered as a manifestation of ischaemia. The regions affected by
      myocardial infarction it may indicate an aneurysm or dyskinesis and is considered
      as a manifestation myocardial ischaemia and a marker of poor prognosis. An
      adequate heart rate is presently considered significant. Sensitivity of the test
      is increased by ECG registration up to 8 to 10 minutes of the recovery phase.

PMID- 14584432
TI  - [The ECG in acute non-cardiac states].

PMID- 14584433
TI  - [Operating in a wheelchair, running a rehabilitation clinic blind... Physicians
      with disability: silent heroes or a risk?].

PMID- 14584434
TI  - [Requiem for hormone replacement therapy? This does not apply to modern
      preparations!].

PMID- 14584435
TI  - [Patients with "environmental illnesses". Umpteen thousand euros unnecessarily
      wasted?].

PMID- 14584436
TI  - [Abused spouses. How colleagues deal with this (interview by Dr. med. Kirsten
      Westphal)].

PMID- 14584437
TI  - [Pneumonia in the alcoholic patient leads to lung abscess despite treatment.
      Sometimes a different antibiotic is enough].

PMID- 14584438
TI  - [Hemangioma in the infant. Freezing, laser treatment--or waiting?].

PMID- 14584439
TI  - [Magnetic field in osteoporosis. Bone density promotion or quackery? (interview
      by Dr. Judith Neumaier)].

PMID- 14584440
TI  - [Arterial occlusive disease. Important marker for myocardial infarct and stroke].

PMID- 14584441
TI  - [Risk of vascular occlusion in your patient? With the ankle-arm index general
      practitioners discover the risk much earlier].

PMID- 14584442
TI  - [Characteristics of diagnosis of peripheral arterial occlusive disease in
      diabetic patients. This pitfall should be avoided].
AB  - Doppler pressure measurement with determination of the ankle-arm indices, and
      duplex ultrasonography, together form the basis of the diagnostic investigation
      of the vascular system in diabetics. MR angiography and arteriography are not
      screening methods in suspected peripheral blood flow disorders. MR angiography
      should be applied only when findings are unclear and the therapeutic consequences
      uncertain. Invasive therapeutic measures (angioplasty, vascular surgery,
      amputation) must still be preceded by intra-arterial digital subtraction
      angiography as the method of choice.

PMID- 14584443
TI  - [Questionnaire study of stroke, myocardial infarct and arterial occlusive
      disease. What are the risk factors in Germans?].

PMID- 14584444
TI  - [Diagnosis of arterial vascular diseases with duplex sonography. Often better
      than angiography].
AB  - Color-coded duplex ultrasonography has decisively improved the noninvasive
      diagnostic possibilities in angiology. It is side effect-free, repeatable
      whenever required and, in experienced hands, can be performed within a reasonable
      time. In contrast, arterial angiography is a purely diagnostic but invasive
      procedure with an associated complication rate of 0.5% [25]. Color-coded duplex
      ultrasonography is an effective and inexpensive diagnostic method. The overall
      cost of such an examination is about 120 euros [25]; this contrasts with overall
      costs of 939 euros for MR angiography, and 1297 euros for an intra-arterial
      angiography.

PMID- 14584445
TI  - [Wrapping in damp cloth, drinking electrolytes or infusions. What to do when fit
      men collapse?].

PMID- 14584446
TI  - [Diarrhea, tachycardia, impotence. When the nerves fail in diabetic patients].

PMID- 14584447
TI  - [Longevity promoting beta blocker. Soon in 1st place in heart failure?].

PMID- 14584448
TI  - [For every hypertensive patient a diuretic first? "Not advisable in diabetic
      patients"].

PMID- 14584449
TI  - [Influenza vaccination? An extra vaccine for seniors?].

PMID- 14584450
TI  - [Osteoporosis. Don't forget the men!].

PMID- 14584451
TI  - [Therapy of hypertension. Also pulse pressure must be reduced].

PMID- 14584452
TI  - [Insulin resistance and atherosclerosis. Controlling diabetes on 2 fronts].

PMID- 14584453
TI  - [Mammography].

PMID- 14584454
TI  - [Anxiety and social support in a group of young people with insulin-dependent
      diabetes].
AB  - One-hundred and one persons with IDDM and two-hundred and seventeen healthy
      persons between seven and nineteen years old participated in this study. They
      were given the Beck Anxiety Inventory (BAI) and the Multidimensional Scale of
      Perceived Social Support (EMASP) to measure anxiety and social support,
      respectively. Diabetic youth were also given the Questionnaire for Children and
      Adolescents with IDDM. Frequencies, correlations, and t-test analysis were used.
      No significant relationships were found between glycemic control (HbA1c),
      anxiety, and social support. There were no significant differences in anxiety and
      social support between youth with or without IDDM. Those diabetics that follow
      their dietetic regimen had less anxiety. Those that take care of their condition
      perceived more social support. The high percentage (59.1%) of inadequate glycemic
      control among this diabetic population evidenciates the importance of further
      studying their psychological profile in order to identify the associated
      variables and create preventive and therapeutic interventions.

PMID- 14584455
TI  - [Young people and violence: an academic-community focus to address a public
      health problem].

PMID- 14584456
TI  - [Psychotherapy of the child and adolescent with depression].
AB  - This article is a revision of the literature on psychotherapy for children and
      adolescents suffering depression. Based on the findings, psychotherapy,
      particularly cognitive-behavioral interventions are recommended over
      pharmaceutical treatments. Etiological factors seem to indicate that family
      systems therapy to be appropriate for depression in children. Included are
      recommendations for prevention.

PMID- 14584458
TI  - In memoriam--Jose Del Castillo, neurophysiologist (1920-2002).

PMID- 14584457
TI  - [Bulimic and depressive symptomatology in Puerto Rican adolescents].
AB  - Bulimia nervosa and depression have been identified as frequent mental health
      problems among adolescents. Bulimia nervosa, an eating disorder has been
      associated with depression especially among female population. The literature has
      established a high comorbidity between these disorders. Although depression was
      initially conceptualized as an adult disorder, recent research evidenced this
      disorder among adolescents. For this study, it was hypothesized that participants
      who presented bulimic symptomatology were going to present a higher depressive
      symptomatology than those who had no bulimic symptoms. The Bulimia Test (Bulit)
      and the Children's Depression Inventory (CDI) were administered to 309 students
      from a private high school in San Juan, Puerto Rico. Correlation analyses and
      group comparisons were performed to investigate the relationship between bulimia
      nervosa and depression among participants. As hypothesized, a significant
      correlation (p < .01) was found between depression and bulimia nervosa
      symptomatology. Females showed a higher average of bulimic symptomatology than
      males. Early identification for treatments with bulimia and depression would be
      helpful in preventing future problems in later adulthood. Implications of this
      study are discussed.

PMID- 14584460
TI  - Searching for the next tamoxifen.

PMID- 14584459
TI  - The body on fire.

PMID- 14584461
TI  - A frail body but a firm hand.

PMID- 14584462
TI  - Going to waste?

PMID- 14584463
TI  - The lessons from patients.

PMID- 14584464
TI  - Bioterror. Giving science a safety check.

PMID- 14584465
TI  - Diabetes and your kidneys. Monitoring kidney function is crucial for diabetics.

PMID- 14584466
TI  - Insight into cataract surgery. Improved implanted lenses boost benefits from
      cataract surgery.

PMID- 14584467
TI  - Dementia: it's not just about Alzheimer's. Other distinct forms exist.

PMID- 14584468
TI  - A "polypill" a day keeps heart disease away.

PMID- 14584469
TI  - Blood test may predict MS progression.

PMID- 14584470
TI  - Lower death rates among walkers with diabetes.

PMID- 14584471
TI  - Top heart failure drugs compared.

PMID- 14584472
TI  - At-home Alzheimer's test may do more harm than good.

PMID- 14584473
TI  - Hospice nurses: patients who refuse food and water die peacefully.

PMID- 14584474
TI  - MRI helps detect breast cancer in high-risk women.

PMID- 14584475
TI  - Radiation beats tamoxifen after DCIS treatment.

PMID- 14584476
TI  - Early treatment for mild hepatitis C questioned.

PMID- 14584477
TI  - Questions and answers. I am a 65-year-old woman who gets frequent urinary tract
      infections. What can I do to prevent recurrences?

PMID- 14584478
TI  - Questions and answers. Why do I sometimes get abdominal cramps and diarrhea when
      I eat sugar-free of low-calorie foods?

PMID- 14584479
TI  - Role of beta-blocker therapy in the post-myocardial infarction patient with and
      without left ventricular dysfunction.

PMID- 14584481
TI  - Medical image. Muscular emesis.

PMID- 14584480
TI  - A comment on "Aspiration risk after stroke: comparison of clinical examination
      and fiberoptic endoscopic evaluation of swallowing" (Dysphagia 17:214-218, 2002).

PMID- 14584482
TI  - [Tips and tricks in kidney surgery].

PMID- 14584483
TI  - [Retropubic implantation of iodine 125 in the treatment of prostatic cancer].

PMID- 14584484
TI  - [Correct personnel sale].

PMID- 14584485
TI  - [Airway management in adult anesthesia except with the exception of difficult
      intubation. Recommendations of the jury. Short text--2000].

PMID- 14584486
TI  - [Requirements for the management personnel in the hospital of the future].

PMID- 14584487
TI  - Inappropriate sexual comments.

PMID- 14584488
TI  - European Stroke Initiative Recommendations for Stroke Management-update 2003.
AB  - This article represents the update of 'European Stroke Initiative Recommendations
      for Stroke Management', first published in this Journal in 2000. The
      recommendations are endorsed by the 3 European societies which are represented in
      the European Stroke Initiative: the European Stroke Council, the European
      Neurological Society and the European Federation of Neurological Societies.

PMID- 14584489
TI  - Design and baseline characteristics of the stroke prevention by aggressive
      reduction in cholesterol levels (SPARCL) study.
AB  - Evidence suggests that statin therapy reduces the risk of stroke in patients with
      coronary heart disease (CHD), but its benefit for patients with cerebrovascular
      disease and no history of CHD remains uncertain. The Stroke Prevention by
      Aggressive Reduction in Cholesterol Levels (SPARCL) Study is a prospective, multi
      centre, double-blind, randomised, placebo-controlled trial designed to evaluate
      the effects of atorvastatin 80 mg/day in patients who previously experienced a
      stroke or transient ischaemic attack, but who have no known CHD. A total of 4732
      patients have been enrolled, and the data collection phase of the study is
      expected to be completed by October 2004. SPARCL is the first study primarily
      designed to prospectively evaluate the effect of statin treatment in secondary
      stroke prevention.

PMID- 14584490
TI  - Medical image. Colonoscopic and virtual colonoscopic images of colonic polyps.

PMID- 14584491
TI  - [The clinical application of C-reactive protein in prognosis and prevention of
      cardiovascular disease].

PMID- 14584492
TI  - Quality of Medicaid managed care plans' care of children consistently lags behind
      commercial plans' care.

PMID- 14584493
TI  - Many elderly patients with chronic eye disease don't get recommended exams.

PMID- 14584494
TI  - Drug-eluting stents substantially lower rate of restenosis.

PMID- 14584495
TI  - Study finds wide disparities in quality of hospital care.

PMID- 14584496
TI  - Chest X-ray quiz. Posterior rib notching occurring with coarctation of the aorta.

PMID- 14584497
TI  - Itinerant dentists and patent remedies in the Dutch Republic.
AB  - This chapter describes the rise of dentistry in terms of the interaction between
      a changing medical rhetoric and a marketplace under pressure. During the second
      half of the eighteenth century, physicians began to take an active interest in
      surgery. In the corporate health care system of the Dutch Republic, this had far
      reaching consequences for itinerant medical practitioners. Because they were
      pushed out of the market for general surgery, some of them opted for a career in
      dentistry, an alternative in which the regular profession was hardly interested.

PMID- 14584498
TI  - Ahead of the curve or out of the loop? Ten challenges to nuclear medicine
      interconnectivity.

PMID- 14584499
TI  - Transplantation of embryonic stem cells: possibilities and challenges.

PMID- 14584500
TI  - Non-heart-beating donors: is it just a matter of control?

PMID- 14584502
TI  - Guidance for nurse staffing in critical care.

PMID- 14584501
TI  - Early recurrence of an intracardiac sarcoma.

PMID- 14584503
TI  - Report on an international event. Safety of industrial automated systems:
      learning from mistakes--innovative safety technology--focus on the human factor.

PMID- 14584504
TI  - Did you want fries with that trans fat?

PMID- 14584506
TI  - Can Dr. Scholl's relieve your foot and back pain?

PMID- 14584505
TI  - More choices for avoiding the flu this winter.

PMID- 14584507
TI  - Medical devices: cardiovascular devices: reclassification of the arrhythmia
      detector and alarm. Final rule.
AB  - The Food and Drug Administration (FDA) is reclassifying arrhythmia detector and
      alarm devices from class III to class II (special controls). This device is used
      to monitor an electrocardiogram (ECG) and to produce a visible or audible signal
      or alarm when an atrial or ventricular arrhythmia occurs. An atrial or
      ventricular arrhythmia occurs during a premature contraction or ventricular
      fibrillation. FDA is reclassifying this device based on new information contained
      in reclassification petitions regarding the device submitted by the Health
      Industry Manufacturers Association (HIMA) (now known as Advamed), Quinton
      Instrument Co., and Zymed Medical Instrumentation. Elsewhere in this issue of the
      Federal Register, FDA is announcing the availability of the guidance document
      that will serve as the special control for this device. FDA is taking this action
      under the Federal Food, Drug, and Cosmetic Act (the act), as amended by the
      Medical Device Amendments of 1976 (the 1976 amendments), the Safe Medical Devices
      Act of 1990 (the SMDA), the Food and Drug Administration Modernization Act of
      1997 (the FDAMA), and the Medical Device User Fee and Modernization Act of 2002
      (MDUFMA).

PMID- 14584508
TI  - Brain not inflamed? Alzheimer's may not be an inflammation after all.

PMID- 14584509
TI  - Bibliography. Current world literature. Tropical and travel-associated diseases.

PMID- 14584510
TI  - Bibliography. Current world literature. Gastrointestinal infections.

PMID- 14584512
TI  - Can we cope with a shortage of time at work?

PMID- 14584511
TI  - Electronic nose for space program applications.
AB  - The ability to monitor air contaminants in the shuttle and the International
      Space Station is important to ensure the health and safety of astronauts, and
      equipment integrity. Three specific space applications have been identified that
      would benefit from a chemical monitor: (a) organic contaminants in space cabin
      air; (b) hypergolic propellant contaminants in the shuttle airlock; (c) pre
      combustion signature vapors from electrical fires. NASA at Kennedy Space Center
      (KSC) is assessing several commercial and developing electronic noses (E-noses)
      for these applications. A short series of tests identified those E-noses that
      exhibited sufficient sensitivity to the vapors of interest. Only two E-noses
      exhibited sufficient sensitivity for hypergolic fuels at the required levels,
      while several commercial E-noses showed sufficient sensitivity of common organic
      vapors. These E-noses were subjected to further tests to assess their ability to
      identify vapors. Development and testing of E-nose models using vendor supplied
      software packages correctly identified vapors with an accuracy of 70-90%. In
      house software improvements increased the identification rates between 90 and
      100%. Further software enhancements are under development. Details on the
      experimental setup, test protocols, and results on E-nose performance are
      presented in this paper along with special emphasis on specific software
      enhancements.

PMID- 14584513
TI  - Relationship between silicosis and smoking.
AB  - An evaluation of the relationship between silicosis and smoking is important in
      exploring the etiology of silicosis, and the relationship could have an impact on
      studies dealing with silicosis and lung cancer. Data addressing this relationship
      were found in studies designed explicitly to evaluate this association and
      studies that explored other questions. Studies based on compensation registers
      were excluded. Smoking data and methods varied across the studies considered. Of
      the 13 studies, 3 supported the hypothesis that smoking was positively associated
      with silicosis, 8 provided limited support (most included subpopulations showing
      positive associations), and 1 did not support the hypothesis. The only autopsy
      study suggested an inverse association. It is unclear whether the generally
      positive results indicate that smoking predisposes to silicosis or that
      nonspecific radiographic appearances from smoking were interpreted as silicosis
      in some studies. A positive association between radiographic silicosis and
      smoking would bias studies of silicosis and lung cancer, especially those lacking
      smoking data.

PMID- 14584514
TI  - Measuring and identifying large-study metrics for circadian rhythm disruption in
      female flight attendants.
AB  - OBJECTIVES: Flight attendants can experience circadian rhythm disruption due to
      travel through multiple time zones. The objectives of this study were to
      determine whether flight attendants are more likely than teachers (comparison
      group) to experience circadian disruption, as measured by melatonin production,
      and to identify metrics of circadian disruption for epidemiologic studies of
      reproductive health in which biomonitoring is infeasible. METHODS: Each day, for
      one menstrual cycle, 45 flight attendants and 26 teachers kept a daily diary,
      collected and measured their overnight urine, and wore an activity monitor to
      assess sleep displacement. The relation between melatonin production and flight
      attendant and teacher status was analyzed with linear and multiple logistic
      regression. The relation between sleep displacement, melatonin, and flight
      history-derived variables (including time zones crossed) were examined with
      exploratory factor analyses. RESULTS: Flight attendants experience increased
      circadian disruption, as measured by a higher adjusted melatonin rate variance,
      than teachers [2.8 x 10(5) versus 1.0 x 10(5) (ng/hour)2, respectively: P=0.04]
      and are more likely to be in the highest quartile of melatonin variance (odds
      ratio 2.3; 95% confidence interval 0.6-9.1). In the factor analysis, the number
      of time zones crossed was related to both melatonin desynchronization and sleep
      displacement. CONCLUSIONS: Flight attendants experience increased circadian
      disruption, as measured by more variable melatonin rates, than a minimally flying
      comparison group. For epidemiologic studies of flight crews in which melatonin
      measurement is infeasible, the number of time zones crossed is a useful indicator
      of both sleep displacement and melatonin desynchronization.

PMID- 14584515
TI  - Use of Monte Carlo simulation to investigate uncertainty in exposure modeling.
AB  - OBJECTIVES: This study used Monte Carlo (MC) simulation to examine the influence
      of uncertainty on an exposure model and to determine whether a difference exists
      between two worker groups in a ceramic fiber manufacturing plant. METHODS: Data
      on work practices and conditions were gathered in interviews with long-serving
      employees. With the use of previously developed deterministic modeling techniques
      and likely distributions for model parameters, MC simulations generated exposure
      profiles for the two job titles. RESULTS: The exposure profiles overlapped
      considerably, although the average estimated exposure for one job was
      approximately double that of the other. However, when the correlation between the
      model parameters in the two jobs was considered, it was concluded that there was
      a significant difference in the two estimates. CONCLUSIONS: Models are
      increasingly being used to estimate exposure. Different work situations
      inevitably result in different exposure estimates. However, it is difficult to
      determine whether such differences in estimated exposure between worker groups
      are simply the result of uncertainty with respect to the model parameters or
      whether they reflect real differences between occupational groups. This study
      demonstrates the value of MC simulation in helping define the uncertainty in
      deterministic model estimates.

PMID- 14584516
TI  - Method for quantitatively assessing physical risk factors during variable
      noncyclic work.
AB  - OBJECTIVES: Assessing exposure to physical risk factors during variable noncyclic
      work can be problematic. The purpose of this study was to modify an existing data
      reduction method for directly quantifying physical exposures during variable
      noncyclic work. METHODS: Myoelectric activity of the finger flexors of two groups
      of workers, heavy equipment operators (N=25) and mechanics (N=25), was sampled to
      determine the intensity and duration of forceful exertions during normal tasks.
      Data were reduced with a modification of the exposure variation analysis (EVA),
      called clustered EVA (CEVA), using three intensity and two duration categories. A
      two-way, mixed-effects, repeated-measures analysis of variance evaluated the
      percentage of sampled work time in each CEVA category. RESULTS: CEVA was able to
      quantify variable noncyclic work, and it contrasted the work of the two groups,
      with simple effects significantly different for all the exposure categories. The
      mechanics performed high-intensity short-duration contractions 9.1% of the time,
      whereas the operators had similar contractions only 1.8% of the time. Conversely,
      the operators used low-intensity contractions of prolonged duration over 81% of
      the time, compared with only 43% for the mechanics. CONCLUSIONS: CEVA is a useful
      modification of EVA for contrasting the noncyclic work typical of understudied
      industries like construction. A simplification of electromyography with summary
      measures such as CEVA provides a comprehensible, yet accurate measure of forceful
      exertions during worktasks.

PMID- 14584517
TI  - Excessive physical demands in modern worklife and characteristics of work and
      living conditions of persons at risk.
AB  - OBJECTIVES: This study attempted to identify work and leisure-time conditions and
      life-style factors associated with excess metabolic levels (metabolic demands
      exceeding one-third of a person's aerobic capacity) at work among men and women.
      METHODS: The study focused upon psychological, ergonomic, and physically loading
      factors and chemical and physical environmental conditions. Data were obtained
      through self-reports, interviews, workplace analyses, technical measurements, and
      observations. Gender-specific calculations were used in univariate analyses and
      in stepwise logistic regression models for excess metabolic level. RESULTS:
      Twenty-seven percent of the men and twenty-two percent of the women worked at an
      excess metabolic level during their workday. Awkward work postures, heavy manual
      materials handling, high circulatory strain, chemical exposures, noise levels,
      much routine work, and many obstacles to job performance characterized their work
      conditions. The women had low skill discretion and more often atypical workhours,
      while the men showed high circulatory strain during leisure-time activities.
      Important negative life-style factors were a high consumption of alcohol for the
      men and a high body mass index and no or little regular physical exercise for the
      women. CONCLUSIONS: Metabolic demands in worklife today remain high. The women
      who exceeded the recommended metabolic level at work in this study were
      characterized by low pay, poor health, and children at home, in addition to high
      physical load and psychosocial strain at work. These characteristics indicate a
      group with few possibilities to leave a hazardous job for a less physically
      demanding one. The men who worked at an excess metabolic level seemed to be
      characterized more by a life-style common in some male-dominated work cultures
      with monotonous work.

PMID- 14584519
TI  - Lung function impairment in relation to asbestos-induced pleural lesions with
      reference to the extent of the lesions and the initial parenchymal fibrosis.
AB  - OBJECTIVES: The study focused on the effect of pleural lesions on the lung
      function of asbestos-exposed workers. METHODS: A clinical check-up, chest
      radiography, high-resolution computed tomography (HRCT), and lung function
      testing were performed on 162 asbestos-exposed workers without any sign of
      parenchymal fibrosis on their chest radiographs. According to the HRCT scans, two
      subgroups were delineated, 97 subjects with pleural lesions and 65 referents
      without pleural lesions. Four categories of pleural lesions were specified
      according to the extent. Parenchymal changes, if identified on the HRCT scans,
      were recorded. RESULTS: The radiographic sensitivity and specificity for pleural
      lesion detection when compared with that of HRCT were 64.9% and 98.5%,
      respectively. The HRCT scans showed parenchymal abnormalities in 46.3% of the
      participants, more frequently in those with pleural lesions (67.0% versus 15.4%,
      P<0.0001). After the effect of parenchymal fibrosis was taken into account,
      pleural lesions were found to have a significant effect on the decrease in total
      lung capacity, forced vital capacity, and forced expiratory volume in 1 second,
      if being classified into category 2 or higher. CONCLUSIONS: Pleural lesions
      proved to have a negative effect on lung function, depending on their extent. The
      effect of the initial parenchymal fibrosis detectable in the HRCT scans only was
      also significant. A normal chest radiograph does not exclude the presence of
      pleural lesions or initial parenchymal fibrosis, with a possible negative effect
      on lung function.

PMID- 14584518
TI  - Cytogenetic and morphologic subgroups of myelodysplastic syndromes in relation to
      occupational and hobby exposures.
AB  - OBJECTIVES: This study investigated the association between occupational and
      hobby exposure and the risk of myelodysplastic syndromes (MDS) while focusing on
      differential patterns of clonal chromosome aberrations and morphologic subgroups.
      METHODS: A case-referent study was conducted with 330 MDS patients investigated
      cytogenetically in 1976-1993 (cases) and matched referents. Telephone interviews
      with either the person or a next-of-kin were used. The participation rate of the
      cases and referents was 85% and 60%, respectively. Information was obtained from
      the next-of-kin more often for the cases (88%) than for the referents (26%).
      Occupational hygienists assessed the exposure using interview data on worktasks
      and hobbies. Associations with disease risk were evaluated for 10 exposures with
      a logistic regression analysis. RESULTS: The investigated exposures were
      generally not associated with cytogenetically abnormal MDS. Effect estimates for
      specific cytogenetic or morphologic subgroups were generally imprecise.
      Occupational exposure to extremely low-frequency magnetic fields (EMF) was
      associated with MDS with a normal karyotype [odds ratio (OR) 2.0, 95% confidence
      interval (95% CI) 1.0-4.0]. The exposure-response association was consistent for
      intensity but inconclusive for duration. A decreased risk was observed for MDS,
      irrespective of karyotypic pattern, among farmers and farmhands (OR 0.53, 95% CI
      0.35-0.81). CONCLUSIONS: Cytogenetically abnormal MDS was generally not
      associated with occupational or hobby exposure to known or suspected genotoxic
      agents. However, exposure prevalences and intensities were low for several
      agents. An association was suggested between occupational exposure to EMF and MDS
      with a normal karyotype. Biases due to differential information quality and
      selective participation cannot be ruled out.

PMID- 14584520
TI  - Methodological issues in evaluating workplace interventions to reduce work
      related musculoskeletal disorders through mechanical exposure reduction.
AB  - Researchers of work-related musculoskeletal disorders are increasingly asked
      about the evidentiary base for mechanical exposure reductions. Mixed messages can
      arise from the different disciplinary cultures of evidence, and these mixed
      messages make different sets of findings incommensurate. Interventions also
      operate at different levels within workplaces and result in different intensities
      of mechanical exposure reduction. Heterogeneity in reporting intervention
      processes and in measuring relevant outcomes makes the synthesis of research
      reports difficult. As a means of synthesizing the current understanding of
      measures, this paper describes a set of intervention and observation nodes for
      which relevant workplace indicators prior to, during, and after mechanical
      exposure reduction can provide useful information. On the basis of this path of
      impacts from exposure reduction, an approach to the evaluation of multilevel
      ergonomic interventions is described that can assist fellow researchers in
      producing evidence relevant to the challenges faced by workplace parties and
      policy makers.

PMID- 14584521
TI  - Microparticles and nanoparticles as delivery systems for DNA vaccines.
AB  - DNA vaccines, also referred to as genetic vaccines, are generating significant
      preclinical and clinical interest. It has been proven that the expression of an
      antigen or antigens from plasmid DNA (pDNA) may elicit both humoral and cellular
      immune responses. Therefore, DNA vaccines may have potential as new vaccines for
      important pathogens such as HIV, hepatitis C, tuberculosis, and malaria. However,
      the clinical results using "naked" pDNA have been disappointing in the breadth
      and depth of the immune response and the relatively high doses of pDNA needed to
      elicit a response. Clinical trials with the gene gun have been promising, but it
      is unclear whether this technology will be commercially viable. As a result,
      there exists a clear need for new vaccine delivery systems that can be
      administered at low doses to elicit strong humoral and cellular immune responses.
      One promising approach is the development of microparticles and nanoparticles as
      delivery systems for DNA vaccines. In this review, the application of
      microparticles and nanoparticles as DNA vaccine delivery systems will be
      critically reviewed with a primary focus on those systems that have generated in
      vivo immune responses.

PMID- 14584522
TI  - Endothelial cells as therapeutic targets in cancer: new biology and novel
      delivery systems.
AB  - The significance of the endothelial cell as a target for antitumor therapy has
      been recognized for some time, but so far the results of clinical trials
      exploiting this approach have not been encouraging. The subject is likely to gain
      new momentum, however, following a number of important recent findings that shed
      new light on the origins and nature of tumor vasculature. Coupled with rapid
      developments in the use ofphage-displayed peptide libraries to characterize the
      human vascular map, as well as highly selective delivery systems, this new
      understanding of tumor vascular biology should provide many fresh and exciting
      avenues to explore.

PMID- 14584523
TI  - Emerging trends in oral delivery of peptide and protein drugs.
AB  - Most peptide and protein drugs are currently used as parenteral formulations
      because of their poor oral bioavailability. Development of an effective oral
      delivery system for these macromolecular drugs requires a thorough understanding
      of their physicochemical properties, such as molecular weight, hydrophobicity,
      ionization constants, and pH stability, as well as biological barriers that
      restrict protein and peptide absorption from the gastrointestinal (GI) tract,
      including pH variability, enzymatic degradation, and membrane efflux. Various
      strategies currently under investigation include amino acid backbone
      modifications, formulation approaches, chemical conjugation of hydrophobic or
      targeting ligand, and use of enzyme inhibitors, mucoadhesive polymers, and
      absorption enhancers. However, there is only limited success because of the
      hostile environment of the GI tract--e.g., strong pH extremes and abundant
      presence of potent luminal enzymes. This review focuses on the challenges posed
      by the GI system and how different pharmaceutical approaches can be used to make
      oral delivery of protein and peptide drugs more feasible. The roles of P
      glycoprotein and CYP3A4 in controlling the extent of intestinal absorption and
      metabolism will also be discussed.

PMID- 14584524
TI  - Solid dispersions: revival with greater possibilities and applications in oral
      drug delivery.
AB  - Improvement of oral bioavailability of poorly water-soluble drugs remains one of
      the most challenging aspects of drug development. Solid dispersions seem to be a
      viable technique for overcoming this problem. However, the practical
      applicability of these systems has remained limited because of difficulties in
      conventional methods of preparation, poor reproducibility of physicochemical
      properties, difficulties in dosage form development, and lack of feasibility for
      scale-up of manufacturing processes. This review addresses various aspects of
      solid dispersions and compiles some of the recent technology transfers from
      various fields such as the chemical, food, and polymer industries for the
      preparation of solid dispersions that can lead to highly efficient and controlled
      large-scale manufacturing. Some of the practical aspects to be considered for the
      preparation of solid dispersions, such as selection of carrier and methods of
      physicochemical characterization, along with an insight into the release
      mechanism of drugs are also discussed. Finally, an in-depth rationale for limited
      commercialization of solid dispersions and recent revival has been considered.

PMID- 14584525
TI  - On the execution of the death penalty.

PMID- 14584526
TI  - Terrorism and forensic psychiatry.

PMID- 14584527
TI  - Behavioral consequences of infections of the central nervous system: with
      emphasis on viral infections.
AB  - Infections of the central nervous system can damage the brain and cause abnormal
      behavior. In this article, the authors examine how behavior is affected by damage
      to different parts of the brain. They then focus on damage caused by specific
      infections of the brain and how these can result in abnormal behavior with legal
      consequences. Examples of such infections include neurosyphilis, encephalitis
      lethargica, herpes simplex encephalitis, and various other viral encephalitides,
      both acute and chronic. The AIDS dementia complex, which results from HIV
      infection of the brain, causes behavioral abnormalities in addition to motor and
      cognitive impairments. In some cases of violence and other criminal behavior,
      this can be a consequence of central nervous system infection, and the authors
      suggest that criminal sanctions in such events are inappropriate in the absence
      of volitional criminal intent.

PMID- 14584528
TI  - Correlates of adjudicative competence among psychiatrically impaired juveniles.
AB  - This study examines the competence-related abilities of 120 psychiatrically
      hospitalized male juveniles age 10 to 17 years, using the MacArthur Competence
      Assessment Tool-Criminal Adjudication (MacCAT-CA), the Brief Psychiatric Rating
      Scale-Anchored (BPRS-A), the Massachusetts Youth Screening Instrument (MAYSI),
      the Kaufman Brief Intelligence Test (K-BIT), and discharge diagnoses derived from
      file review. The findings indicate significant age-related differences across
      adolescence with a relatively strong performance for most of the youths on the
      competence measure. While intellectual and psychiatric factors were found to
      contribute substantially to deficits in legal decisional ability, they were
      modulated by age and the developmental factors associated with it. These
      findings, replete with caveats concerning both the dimensional structure of
      competence as measured by the MacCAT-CA and the interplay with the mental status
      and developmental factors affecting it, underscore the multifarious nature of
      legal decisional capacity in youths of varying ages. The relevance of these
      findings to the structuring of restoration services and the application of legal
      theory to the competence standard in juvenile court are discussed.

PMID- 14584529
TI  - Commentary: Risk markers for incompetence in juvenile defendants.

PMID- 14584530
TI  - Competency to stand trial in preadjudicated and petitioned juvenile defendants.
AB  - As state legislatures across the United States continue to permit younger
      juvenile defendants to be tried in adult court, juvenile competence to stand
      trial has become an issue of increasing legal and forensic significance. This
      study examined competency to stand trial in a sample of preadjudicated and
      petitioned juvenile defendants. Results revealed that juveniles deemed unfit to
      stand trial were younger than their competent counterparts, had more severe
      special education needs, and had more extensive mental health treatment
      histories. These results are consistent with those of prior research in this
      area. Implications for treatment planning and system reform are discussed.

PMID- 14584531
TI  - Commentary: Children's minds and adult statutes.

PMID- 14584532
TI  - PTSD and the law of psychiatric injury in England and Wales: finally coming
      closer?
AB  - With the increase in terrorism in several parts of the world, more people are
      exposed to traumatic events that could cause psychiatric injury either to them or
      to members of their families. In Britain, terrorist attacks or other catastrophes
      are not unknown; indeed, the case law relating to psychiatric injury is vast.
      However, the intersection between medicine and the law is minimal. The result is
      a law that lags behind the scientific evidence and, on occasion, may seem unfair.

PMID- 14584533
TI  - Commentary: Medical evidence-based law?

PMID- 14584534
TI  - Patterns of denial in sex offenders: a replication study.
AB  - To assess whether a robust typology of sex offenders could be established based
      on the patterns of denial displayed, a previously developed semistructured
      interview method was used to assess denial in a mixed group of convicted rapists
      and child molesters. Cluster analysis was used to establish homogeneous groups of
      sex offenders based on the pattern of denial in each case, with a three-cluster
      solution emerging as the most appropriate, confirming previous research. The
      denial groups were compared in relation to objective offense characteristics to
      assess whether a consistent typology of offenders emerged. Each of the four
      groups of offenders identified (three groups emerging from the cluster analysis
      and an "absolute denier" group) corresponded closely with the previously
      identified typology. However, the authors failed to replicate previously
      identified differences between the denial groups in relation to independent
      variables such as offense type. Each group contained both rapists and child
      molesters and was found to differ quantitatively rather than qualitatively in the
      pattern of the denial expressed, with attributional style being the most
      consistent form of denial present in all groups. The authors conclude that denial
      consists of at least two continuous dimensions, rather than being a dichotomous
      phenomenon. Differences in the patterns of denial displayed by rapists and child
      molesters were found to be primarily quantitative rather than qualitative.

PMID- 14584535
TI  - The influence of French, Spanish, and English legal traditions on early mental
      health proceedings in Louisiana.
AB  - Unlike other jurisdictions in the United States where the basis of the law can be
      traced more exclusively to the common law of England, the legal system in
      Louisiana also has origins in the laws of France and Spain. In this article, the
      authors describe the laws and procedures that developed early in Louisiana's
      history for the involuntary care and civil commitment of the mentally ill,
      focusing on the laws that were passed after the American takeover in 1803.

PMID- 14584536
TI  - Confronting America's most ignored crime problem: the Prison Rape Elimination Act
      of 2003.
AB  - Prisoner sexual assault has plagued American corrections since its infancy in the
      19th century. Although the incidence of prisoner sexual assault is unknown,
      recent studies reliably suggest the problem is widespread, often affecting the
      most vulnerable prisoners. The mental health and public health consequences, both
      within institutions and the community, are complex and devastating, requiring
      comprehensive intervention and treatment. These crimes have been largely ignored
      by correctional managers, compromising the safety and security of correctional
      institutions. The Prison Rape Elimination Act of 2003 could play a vital role in
      managing a national scandal.

PMID- 14584537
TI  - Lifting the curtain of silence: survivors speak about rape behind bars.
AB  - In the struggle to end sexual violence behind bars, personal stories of abuse
      serve as an important advocacy tool for organizations such as Stop Prisoner Rape
      (SPR). The first-person accounts of men and women who have endured this abuse
      help to personalize, and thereby, humanize the issue. Statistics about the
      frequency of prisoner rape are powerful, but they can also be numbing, conveying
      the sense that nothing can be done to stop the problem. Personal accounts in
      contrast, have an emotional impact that encourages action. Speaking out about
      abuse also helps survivors, freeing them from a sense of shame, guilt, and
      humiliation and providing an avenue of political engagement that can be
      tremendously empowering. This article presents the first-persona accounts of four
      individuals whose lives were powerfully affected by rape behind bars.

PMID- 14584538
TI  - Managed care and ERISA: synopsis and case law review.
AB  - Managed care organizations (MCOs) have become the predominant health care model
      in the United States. Through cost containment arrangements with providers,
      incentives for patients to pursue less costly care and reductions in the
      provision of unnecessary care, MCOs are more intimately involved in the delivery
      of health care than their former fee-for-service insurance company counterparts.
      However, this new role has not implied increased liability, largely because of
      The Employee Retirement Income Security Act of 1974 (ERISA). This article
      provides an overview of ERISA and a review of the important legal cases in this
      area, including the three most recent Supreme Court cases. Courts have struggled
      with interpreting ERISA, and decisions have been difficult to reconcile.
      Frustration with this statute and the failure of the U.S. Congress to amend it,
      has led to more liberal interpretations of ERISA in recent years.

PMID- 14584539
TI  - Competency to be executed and forced medication: Singleton v. Norris.
AB  - Singleton v. Norris is a decision by the Eighth Circuit Court of Appeals stating
      that forced psychotropic medication can be continued after the date of execution
      is set if the medication had been given previously to prevent the inmate from
      being dangerous in the prison setting under a Harper-type review. The defendant
      had argued that after the date of execution was set, it was no longer in his
      medical interests to continue the medication. In the decision, the majority held
      that the fact that an execution is in the offing does not alter the medical
      interests for which the medication had been prescribed, and physicians should
      just continue to treat the medical condition. This decision may raise ethics
      problems for physicians in such settings, because they may be in violation of the
      American Medical Association (AMA) Code of Ethics if the original override is
      dubious.

PMID- 14584540
TI  - Causality and collateral estoppel: process and content of recent SSRI litigation.
AB  - In Tobin v. SmithKline Beecham Pharmaceuticals a jury in the U.S. District Court
      for the District of Wyoming found that the medication Paxil "can cause some
      individuals to commit homicide and/or suicide," and that it was a legal cause of
      the deaths in this case. A motion was recently put before the United States
      District Court for the District of Utah to adopt the findings of the Tobin case-
      via the application of collateral estoppel--to a case involving an individual's
      suicide while prescribed Paxil. This article summarizes these two cases, as
      reflected in court documents, and comments on limitations of common causality
      assertions.

PMID- 14584541
TI  - Debate regarding competency-for-trial instruments.

PMID- 14584542
TI  - Terminology in an incorrect and imprecise manner.

PMID- 14584543
TI  - Bursztajn et al. offer two composite case vignettes of lost compensation claims.

PMID- 14584544
TI  - Long-term amnesia: a review and detailed illustrative case study.
AB  - Long-term amnesia is a slowly developing form of anterograde amnesia accompanied
      by retrograde amnesia of variable severity (Kapur, 1996; 1997) often associated
      with damage to the anterior temporal neocortex and epileptic seizures. The
      precise neural and functional deficits that underlie this condition are unknown.
      A patient, JL, who has this condition following a closed-head injury, is
      described in detail. Her injury caused bilateral anterior temporal neocortex
      damage that was more extensive on the left and right-sided damage to the
      perirhinal and orbitofrontal cortices. The hippocampus appeared to be intact
      bilaterally. Epilepsy developed within two years of JL's injury. Apart from her
      memory impairments, JL's cognitive functions, including high-level visual
      perception, attention, semantic memory and executive functions were well
      preserved. Her memory also seemed well preserved for at least 30 minutes
      following encoding. The one exception was the patient's relatively greater
      impairment at difficult visual recognition tests for which verbalization may not
      have been an effective strategy. This problem may have been caused by JL's right
      sided perirhinal and orbitofrontal cortex damage. Her recall and recognition was
      clearly impaired after a three-week delay. She also showed a retrograde amnesia,
      which appeared to be milder than her remote post-morbid memory deficit. JL's
      remote memory was preserved for information first encountered in either the pre-
      or post-morbid period provided the information had received sufficient rehearsal
      over long periods of time. Her long-term amnesia may have been caused by anterior
      temporal neocortex damage, possibly in association with her epileptic seizures.
      Whether the condition is heterogeneous, involves a deficit in slow consolidation,
      disruption of unconsolidated memories, or blockage of maintenance or disruption
      of insufficiently rehearsed memories whether or not these have been slowly
      consolidated is discussed.

PMID- 14584545
TI  - A case of amnesia at an early age.
AB  - A dissociation between short- and long-term memory (LTM) and between the episodic
      and the semantic component of LTM is reported in a young girl who became amnesic
      at the age of 6 after an episode of acute encephalopathy resulting in bilateral
      frontal, insular, thalamic, ponto-mesencephalic, hippocampal and temporal
      lesions, as documented by MRI. The girl became amnesic a few months after
      starting school. A follow-up investigation showed that she was able to learn to
      read, write and acquire number facts and procedures and to improve her semantic
      knowledge. Our results show that the features of adult amnesia can also be found
      in children and that new semantic knowledge can be acquired in spite of an
      anterograde memory deficit. This dissociation does not agree with theories
      viewing long-term declarative memory as a unitary process mediated by the
      hippocampal system, but supports recent hypotheses that the acquisition of
      semantic knowledge is independent from episodic memory processes, and takes place
      through spared cortical regions subjacent to the hippocampi (Vargha-Khadem et
      al., 1997).

PMID- 14584546
TI  - Hemispheric asymmetries in memory processes as measured in a false recognition
      paradigm.
AB  - Although memory differs in important ways between the left and right cerebral
      hemispheres, the nature of these differences remains controversial. We examined
      this issue in two experiments using a false memory paradigm that allowed novel
      tests of two theories that have not been assessed in a common paradigm
      previously. Lists of semantically related words (e.g., bed, rest, wake...), all
      highly associated to one "critical" word (e.g., sleep), were presented auditorily
      during a study phase. Memory for both the related words and the critical words
      was measured in a subsequent old/new recognition test using divided-visual-field
      word presentations. The most important results were that the ability to correctly
      reject previously unpresented words was greater when test items were presented to
      the right visual field/left hemisphere (RVF/LH) than to the left visual
      field/right hemisphere (LVF/RH) and that participants were more confident in
      correctly rejecting unpresented words when test items were presented to the
      RVF/LH than to the LVF/RH. Results were in line with the theory that associative
      activation of semantic information is restricted in the left hemisphere but
      diffuse in the right; however, these results contrasted with the theory that
      memory traces are interpretive in the left hemisphere but veridical in the right.
      A potential resolution to the seemingly contradictory theories of asymmetries in
      memory processing is briefly discussed.

PMID- 14584547
TI  - Engagement of lateral and medial prefrontal areas in the ecphory of sad and happy
      autobiographical memories.
AB  - Autobiographic memory is usually affect-laden, either positively or negatively. A
      central question is whether the retrieval of both emotive forms of memory engages
      the same or a different neural net. To test this we studied 13 normal subjects
      with functional magnetic resonance imaging while they retrieved a number of
      distinct episodes, all of which were either rated as strongly positive (happy) or
      strongly negative (sad) in affect. Comparing the retrieval of sad with that of
      happy episodes revealed activation in both lateral orbital cortices symmetrically
      (extending into the ventrolateral prefrontal cortex as well), together with a
      small region in the right lateral temporal cortex and the left cerebellum. Vice
      versa, comparing the retrieval of happy with that of sad episodes revealed a
      major activation in the left hippocampal region, bilateral (though more right
      sided) activation in the medial orbitofrontal/subgenual cingulate and a left
      sided activation in the dorsolateral prefrontal activation. These findings point
      to the importance of the orbitofrontal cortex for affect-laden information
      processing and to the existence of distinct neural nets for the re-activation of
      positively and negatively viewed autobiographic episodes.

PMID- 14584548
TI  - Disruption of inhibitory control of memory following lesions to the frontal and
      temporal lobes.
AB  - A group of patients with lesions to the frontal lobes, a group with lesions to
      the temporal lobes, and groups of non-brain damaged controls took part in three
      experiments. The first experiment used directed forgetting (DF) by items, the
      second DF by lists, and the third retrieval induced forgetting (RIF). Frontal
      patients with right side lesions could not intentionally inhibit but all frontal
      patients showed normal RIF. Temporal patients with left side lesions had abnormal
      DF by lists and all the temporal patients had abnormal RIF. These findings are
      explained in terms of impairment to executive thought avoidance control processes
      in frontal patients and impaired knowledge access to long-term memory in temporal
      patients.

PMID- 14584549
TI  - The neuropsychology of autobiographical memory.
AB  - This special issue of Cortex focuses on the relative contribution of different
      neural networks to memory and the interaction of 'core' memory processes with
      other cognitive processes. In this article, we examine both. Specifically, we
      identify cognitive processes other than encoding and retrieval that are thought
      to be involved in memory; we then examine the consequences of damage to brain
      regions that support these processes. This approach forces a consideration of the
      roles of brain regions outside of the frontal, medial-temporal, and diencephalic
      regions that form a central part of neurobiological theories of memory. Certain
      kinds of damage to visual cortex or lateral temporal cortex produced impairments
      of visual imagery or semantic memory; these patterns of impairment are associated
      with a unique pattern of amnesia that was distinctly different from the pattern
      associated with medial-temporal trauma. On the other hand, damage to language
      regions, auditory cortex, or parietal cortex produced impairments of language,
      auditory imagery, or spatial imagery; however, these impairments were not
      associated with amnesia. Therefore, a full model of autobiographical memory must
      consider cognitive processes that are not generally considered 'core processes,'
      as well as the brain regions upon which these processes depend.

PMID- 14584550
TI  - Two further investigations of autobiographical memory in semantic dementia.
AB  - A number of investigations in semantic dementia have documented better retrieval
      of recent personal events compared to those in the more distant past (Graham and
      Hodges, 1997). Westmacott et al. (2001) challenged this result, however, finding
      relative preservation of remote memories in a single case of semantic dementia
      when he was tested using family photographs. In Experiment 1, we tested two
      possible explanations for the discrepancy between the published papers: (a) that
      there is a significant effect of modality in autobiographical retrieval in
      semantic dementia (e.g., patients will show better, or even preserved, remote
      memory when tested on nonverbal, compared to verbal, tasks); and (b) that the
      distinct pattern seen between patients is attributable to the different methods
      adopted for scoring the episodic quality of the memories. A patient with semantic
      dementia, AM, produced autobiographical memories to both words and family
      photographs. These personal events were scored by two raters using the scoring
      method described by Westmacott et al. (2001) and that reported by Graham and
      Hodges (1997). It was found that AM showed similar levels of remote memory
      impairment regardless of whether the cue was verbal or nonverbal. In addition,
      significant effects of time were revealed in AM's performance on the verbal
      memory test, regardless of which method was used to score the memories. In
      Experiment 2, we investigated a related question: whether the relatively better
      retrieval of memories in semantic dementia could be due to over rehearsal of
      highly salient recent experiences? Four patients were tested on their ability to
      remember a recent event (either a trip to London or events from a Formula One
      Grand Prix race) using specially designed autobiographical questionnaires. It was
      found that all four were able to perform this task, although one patient showed
      evidence of some forgetting over three months, and another exhibited difficulty
      discriminating between two similar events. Together, the two experiments further
      confirm that patients with semantic dementia show a modality independent
      autobiographical memory deficit, with better retrieval of recent events.

PMID- 14584551
TI  - New learning and remote memory in atypical Alzheimer's disease.
AB  - This paper presents the case of BB, an individual with an atypical posterior
      cortical presentation of Alzheimer's disease (AD). The severity of BB's visuo
      spatial impairment far outweighed impairment of other cognitive functions. BB's
      case is also unusual in that despite a long history of progressive impairment,
      his cognitive symptoms remain relatively circumscribed. More specifically, BB's
      pattern of memory impairment was striking, since his impairment on formal
      psychometric tests of memory contrasted with his performance at clinical
      interview, where he talked lucidly about events in his past, and displayed
      remarkably well-preserved general semantic knowledge. On the basis of BB's
      clinical profile, it was hypothesised that his pattern of cognitive performance
      reflected an impairment of anterograde memory in the context of relative
      preservation of remote memory. Further investigations revealed that while BB's
      anterograde memory function was comparable to that of other AD patients, his
      remote memory was well preserved relative to other AD 'controls'. These findings
      are discussed in terms of typical and atypical presentations of Alzheimer's
      disease, and in terms of the possible fractionation of different aspects of long
      term memory. The implications of these findings for our understanding of the
      neural bases of different types of retrograde memory (i.e. 'old' versus 'recent')
      are considered, with particular reference to the contrasting theoretical
      frameworks that have recently been advanced by Squire and Moscovitch.

PMID- 14584552
TI  - The impact of disrupted cortico-cortico connectivity: a long-term follow-up of a
      case of focal retrograde amnesia.
AB  - We report a long-term follow-up study of case JM, who demonstrated a focal
      retrograde amnesia (FRA) as a consequence of cerebral vasculitis. The present
      study showed that, several years post-onset, JM experienced considerable
      impairment in episodic retrograde memory, with normal anterograde
      autobiographical memory. Further investigations demonstrated that she showed no
      evidence of accelerated forgetting, unlike some other cases of FRA. Knowledge of
      people, pre- and post-illness, was also normal. Her ability to recall details of
      famous public events was good (though weaker for pre-illness events). JM's
      pattern of impairment is discussed in the context of other recent cases of FRA
      and developments in models of normal memory function.

PMID- 14584553
TI  - Encoding and the frontal lobes: a dissociation between retrograde and anterograde
      memories.
AB  - Recent functional neuroimaging studies have suggested that different neural
      substrates within the frontal lobes are associated with memory encoding,
      retrieval and monitoring. If this is the case, then it should be possible to find
      frontal patients with selective deficits to these processes. However, most
      laboratory based memory tests (e.g. Wechsler Memory Scale) require a combination
      of all these processes making it hard to find clear dissociations between
      patients. Using tests of everyday memory, this study documents a clear
      dissociation between a frontal patient's (JB) impaired ability to retrieve events
      from the anterograde period relative to spared ability to retrieve events from
      the retrograde period. This is consistent with specific disruption to frontal
      mechanisms associated with encoding which disrupts the formation of new episodic
      memories. The defective mechanism may be related to more general aspects of
      cognitive processing (e.g. selection demands), but it is unlikely to reflect
      damage to working memory (as assessed by the n-back task) as there is a clear
      dissociation between spared performance on this task and impaired performance on
      a comparable episodic recognition memory task.

PMID- 14584554
TI  - A cholinergic explanation of dense amnesia.
AB  - Traditionally, dense amnesia in humans has been thought to be caused by damage to
      memory structures within the medial temporal lobe, either the hippocampus, the
      perirhinal cortex or a combination of the two. Recent work in animals has
      indicated that damage to the hippocampus results in memory impairments that are
      specific to memories for events. In contrast, damage to the perirhinal cortex
      impairs object memories in primates, which are likely to be analogous to human
      semantic memory. Discrete damage to either of these structures does not appear to
      result in severe and global memory impairments. We propose an alternative to this
      medial temporal lobe explanation of dense amnesia, based on our recent work. We
      have shown that the cholinergic cells of the basal forebrain are essential for
      new learning of both object and event-like memories in the monkey. Our model of
      learning in the primate brain rests on the proposal that there is a route of
      communication between the frontal cortex and inferior temporal cortex and
      hippocampus via the basal forebrain, which is critical for memory encoding.
      Interruption to this circuit at any stage will result in a severe and global
      anterograde amnesia.

PMID- 14584555
TI  - Remembering and knowing in patients with frontal lobe injuries.
AB  - Two experiments compared the performance of patients with pathology restricted to
      the prefrontal cortex to healthy controls on recognition tests that were followed
      by the remember/know procedure. Across both experiments, patients recognized
      roughly as many target items as control participants. Injuries centered in the
      frontal poles resulted in deficits that were selective to episodic remembering
      while apparently sparing semantic knowing. Patients with lesions restricted to
      dorsolateral prefrontal cortex were not impaired at either remembering or
      knowing. Results demonstrate a dissociation of cognitive function within the
      prefrontal cortex, and suggest that episodic remembering may share a family
      resemblance with other neurocognitive functions dependent upon polar aspects of
      the frontal lobes, such as self-recognition, anticipation, and planning.

PMID- 14584556
TI  - Role of the frontal lobes in implicit and explicit retrieval tasks.
AB  - While the role of the frontal lobes in explicit retrieval tasks is well
      supported, the findings for implicit tasks are less conclusive. We investigated
      the role of the frontal lobes in perceptual and conceptual implicit priming.
      Three memory paradigms were given under both implicit and explicit retrieval
      instructions, using word fragment completion, picture fragment completion and
      category exemplar generation. Three groups of individuals with frontal lesions
      were compared to normal controls: Left dorsolateral lesions (n = 5), right
      dorsolateral lesions (n = 4), and medial lesions (n = 9). Word fragment
      completion priming was impaired by left dorsolateral lesions, with other priming
      tests unaffected by any lesion. Explicit performance showed a different pattern,
      with category exemplar cued recall impaired by left dorsolateral and medial
      lesions. These findings support the role of the frontal lobes in both implicit
      and explicit retrieval mechanisms under certain conditions requiring strategy
      application or lexical retrieval.

PMID- 14584557
TI  - Frontal cortex as the central executive of working memory: time to revise our
      view.
AB  - For historical reasons (Bianchi, 1895; Harlow, 1968; Luria, 1966; Shallice,
      1982), a specific link between the central executive of working memory and the
      frontal cortex was originally suggested by Baddeley (1986). This review discusses
      the evidence against such a univocal link. Two executive processes investigated
      in neuropsychology are discussed: inhibition (WCST, Stroop, proactive
      interference, go-no go, Stop signal and the Hayling test) and dual-task
      management. The evidence reviewed demonstrates (i) that executive processes
      involve links between different brain areas, not exclusively with the frontal
      cortex, (ii) that patients with no evidence of frontal damage present with
      executive deficits, and (iii) that patients with frontal lesions do not always
      show executive deficits. In conclusion, this review suggests that it is time for
      a more dynamic and flexible view of the neural substrate of executive processes
      to be considered. It also confirms, as recently suggested by Baddeley (1996,
      1998a, 1998b), that the study of frontal patients cannot be used as a primary
      source of evidence to understand CE functions.

PMID- 14584558
TI  - Evidence for quantitative domain dominance for verbal and spatial working memory
      in frontal and parietal cortex.
AB  - Neuroimaging studies in humans have shown that different working memory (WM)
      tasks recruit a common bilateral fronto-parietal cortical network. Animal studies
      as well as neuroimaging studies in humans have suggested that this network, in
      particular the prefrontal cortex, is preferentially recruited when material from
      different domains (e.g. spatial information or verbal/object information) has to
      be memorized. Early imaging studies have suggested qualitative dissociations in
      the prefrontal cortex for spatial and object/verbal WM, either in a left-right or
      a ventral-dorsal dimension. However, results from different studies are
      inconsistent. Moreover, recent fMRI studies have failed to find evidence for
      domain dependent dissociations of WM-related activity in prefrontal cortex. Here
      we present evidence from two independent fMRI studies using physically identical
      stimuli in a verbal and spatial WM task showing that domain dominance for WM does
      indeed exist, although only in the form of quantitative differences in activation
      and not in the form of a dissociation with different prefrontal regions showing
      mutually exclusive activation in different domains. Our results support a mixed
      dimension model of domain dominance for WM within the prefrontal cortex, with
      left ventral prefrontal cortex (PFC) supporting preferentially verbal WM and
      right dorsal PFC supporting preferentially spatial WM. The concept of domain
      dominance is discussed in the light of recent theories of prefrontal cortex
      function.

PMID- 14584559
TI  - Segregation of the neural correlates of language and phonological short-term
      memory.
AB  - A left-handed patient is reported who developed a selective deficit of
      phonological short-term memory, but not aphasia, following an ischaemic lesion in
      the temporal parietal region of the left hemisphere The phonological short-term
      store was selectively damaged compared to the rehearsal system. The patient also
      showed impaired comprehension of spoken (but not written) connected language.
      This study suggests that language and phonological short-term memory may be
      mediated by segregated neural systems that develop independently in the two
      hemispheres. The relationship between phonological short-term memory and auditory
      comprehension is also discussed.

PMID- 14584560
TI  - Seeking the neural substrates of visual working memory storage.
AB  - It is widely assumed that the prefrontal cortex (PFC) is a critical site of
      working memory storage in monkeys and humans. Recent reviews of the human lesion
      literature and recent neuroimaging results, however, challenge this view. To test
      these alternatives, we used event-related fMRI to trace the retention of working
      memory representation of target faces across three delay periods that were
      interposed between the presentation of each of four stimuli. Across subjects,
      only posterior fusiform gyrus demonstrated reliable retention of target-specific
      activity across all delay periods. Our results suggest that no part of frontal
      cortex, including PFC, stores mnemonic representation of faces reliably across
      distracted delay periods. Rather, working memory storage of faces is mediated by
      a domain-specific network in posterior cortex.

PMID- 14584561
TI  - Dissociating aspects of temporal and frequency processing: a functional ERP study
      in humans.
AB  - An event-related potential (ERP) study was conducted, in order to dissociate
      brain functions associated with temporal information processing and processing of
      frequency information. Twelve participants were presented with both a temporal
      generalization and a pitch generalization task. In both tasks, exactly the same
      set of stimuli was presented to prevent stimulus-specific influences on ERP
      patterns. Participants had to decide whether or not an auditory stimulus matched
      a previously memorized standard stimulus, either with respect to pitch or
      duration. Analysis of ERPs revealed an increased negativity for the temporal
      discrimination task at fronto/central electrode sites. This effect was observed
      between 150 msec and 1,000 msec. At posterior sites, however, there was an
      increased positivity between 500 and 1,000 msec for the temporal generalization
      task. The differential topological activation patterns suggest more pronounced
      utilization of executive working-memory ressources for processing of temporal
      than for processing of pitch information.

PMID- 14584562
TI  - Event-induced theta responses as a window on the dynamics of memory.
AB  - An important, but often ignored distinction in the analysis of EEG signals is
      that between evoked activity and induced activity. Whereas evoked activity
      reflects the summation of transient post-synaptic potentials triggered by an
      event, induced activity, which is mainly oscillatory in nature, is thought to
      reflect changes in parameters controlling dynamic interactions within and between
      brain structures. We hypothesize that induced activity may yield information
      about the dynamics of cell assembly formation, activation and subsequent
      uncoupling, which may play a prominent role in different types of memory
      operations. We then describe a number of analysis tools that can be used to study
      the reactivity of induced rhythmic activity, both in terms of amplitude changes
      and of phase variability. We briefly discuss how alpha, gamma and theta rhythms
      are thought to be generated, paying special attention to the hypothesis that the
      theta rhythm reflects dynamic interactions between the hippocampal system and the
      neocortex. This hypothesis would imply that studying the reactivity of scalp
      recorded theta may provide a window on the contribution of the hippocampus to
      memory functions. We review studies investigating the reactivity of scalp
      recorded theta in paradigms engaging episodic memory, spatial memory and working
      memory. In addition, we review studies that relate theta reactivity to processes
      at the interface of memory and language. Despite many unknowns, the experimental
      evidence largely supports the hypothesis that theta activity plays a functional
      role in cell assembly formation, a process which may constitute the neural basis
      of memory formation and retrieval. The available data provide only highly
      indirect support for the hypothesis that scalp-recorded theta yields information
      about hippocampal functioning. It is concluded that studying induced rhythmic
      activity holds promise as an additional important way to study brain function.

PMID- 14584563
TI  - The role of theta-range oscillations in synchronising and integrating activity in
      distributed mnemonic networks.
AB  - It is well established that the occurrence of theta rhythm in the hippocampus is
      important in a variety of mnemonic tasks. However, in this review it will be
      argued that theta-rhythmic activity occurs across distributed networks within the
      diencephalon and neocortex as well as the hippocampus, and functions to
      temporally coordinate activity in distributed systems within these regions during
      mnemonic processes. Recent evidence strongly suggests that theta-range cellular
      activity occurs in the supramammillary nucleus (SuM) of the hypothalamus, and
      that this activity is independent of that occurring in the hippocampus. We have
      previously proposed in fact, that the frequency of theta activity in the
      hippocampus is determined in the SuM, rather than in the medial septum as
      previously assumed. The frequency-coded information from the SuM is then fed into
      at least two recurrent networks proposed by Aggleton and Brown (1999). Theta
      activity in these networks (the hippocampo-anterior thalamic system and the
      perirhinal-mediodorsal thalamic system) could potentially occur independently,
      but when simultaneously occurring in both may function to coordinate the
      integration of information in the two systems. Finally, we suggest that as the
      two systems include temporal and frontal neocortical areas that contribute to
      surface EEG, scalp recording of theta EEG activity from these regions may provide
      a "window" through which to assess the relative involvement of different cortico
      limbic circuits in different mnemonic processes. The potential utility of this
      technique will be increased greatly by the use of high-density EEG and algorithms
      to more precisely map the topography of cortical sources of EEG activity.

PMID- 14584564
TI  - Regional brain activations predicting subsequent memory success: an event-related
      fMRI study of the influence of encoding tasks.
AB  - We determined the brain regions that were differentially sensitive to two,
      randomly inter-mixed tasks: Deep Encoding, in which subjects processed items
      according to their meaning (is the word pleasant or unpleasant?) and Shallow
      Encoding, in which items were processed according to two underlined letters in
      the word (are the letters in alphabetical order?). The former task was associated
      with activations in a set of brain regions including left lateral prefrontal
      cortex (PFC) and left medial temporal cortex. The latter showed relatively
      greater activation in right PFC. Both findings are consistent with predictions
      made on the basis of previous functional neuroimaging work. Following scanning,
      each subject underwent a recognition memory task. The results of these provided
      the basis for a further sub-division of encoding events, according to whether
      they were predictive of subsequent recognition success or not. Unsurprisingly,
      recognition performance was greater for words that had been deeply encoded. For
      both encoding conditions, words that were subsequently recognised were associated
      with greater activation in a sub-set of regions identified by the deep versus
      shallow contrast. These included left PFC and medial temporal regions. In left
      PFC this performance-predicting activation was significantly greater for the deep
      encoding condition. Our results support previous studies suggesting a role for
      left PFC and medial temporal cortex in episodic memory encoding. They provide
      more evidence, too, for a less consistent finding: the interaction between the
      encoding task and the success of subsequent recognition.

PMID- 14584565
TI  - FDG-PET findings in the Wernicke-Korsakoff syndrome.
AB  - This study reports FDG-PET findings in Wernicke-Korsakoff patients. Twelve
      patients suffering amnesia arising from the Korsakoff syndrome were compared with
      10 control subjects without alcohol-related disability. Subjects received [18F]
      fluorodeoxyglucose (FDG-PET) imaging as well as neuropsychological assessment and
      high-resolution MR imaging with volumetric analysis. Volumetric MRI analysis had
      revealed thalamic and mamillary body atrophy in the patient group as well as
      frontal lobe atrophy with relative sparing of medial temporal lobe structures.
      Differences in regional metabolism were identified using complementary region of
      interest (ROI) and statistical parametric mapping (SPM) approaches employing
      either absolute methods or a reference region approach to increase statistical
      power. In general, we found relative hypermetabolism in white matter and
      hypometabolism in subcortical grey matter in Korsakoff patients. When FDG uptake
      ratios were examined with occipital lobe metabolism as covariate reference
      region, Korsakoff patients showed widespread bilateral white matter
      hypermetabolism on both SPM and ROI analysis. When white matter metabolism was
      the reference covariate; Korsakoff patients showed relative hypometabolism in the
      diencephalic grey matter, consistent with their known underlying neuropathology,
      and medial temporal and retrosplenial hypometabolism, interpreted as secondary
      metabolic effects within the diencephalic-limbic memory circuits. There was also
      evidence of a variable degree of more general frontotemporal neocortical
      hypometabolism on some, but not all, analyses.

PMID- 14584566
TI  - Contributions of thalamic nuclei to declarative memory functioning.
AB  - In spite of the acknowledged role that the thalamus plays in declarative memory,
      details about the precise memory processes it is involved in and which are the
      structures of the thalamus that contribute to these processes remain unknown. An
      overview is presented of human clinical and animal experimental findings showing
      the involvement of the thalamus, at the level of white matter tracts and separate
      nuclei, in aspects of memory functioning. The region in the thalamus that
      contributes to declarative memory is the anterior and medial division, containing
      the anterior nuclei, the medial dorsal nucleus and the intralaminar and midline
      nuclei. A lesion to the anterior nuclei or their afferent white matter tract, the
      mammillothalamic tract, results in deficits of encoding of new stimuli. Lesions
      to the medial dorsal nucleus affect executive processes pertaining to declarative
      memory, such as the use of memory strategies for retrieval; damage to the
      intralaminar and midline nuclei results in decreased arousal and thus affects the
      declarative memory process. Based on anatomical and functional data, a theory is
      proposed of how the thalamus might play a role at different levels of declarative
      memory functioning. Firstly, the anterior and mediodorsal nucleus are involved in
      processing the contents of the stimuli for storage and recall. The anterior
      nuclei influence the selection of material to be stored and remembered, whereas
      the mediodorsal nucleus is involved in the coordination and selection of the
      strategies used to retrieve material. Secondly, the intralaminar and midline
      nuclei and specifically the lateral and ventral components, maintain a necessary
      state of the cortical regions involved in the ongoing memory processes. The two
      types of function subserved by these groups of thalamic nuclei, focussing on
      contents vs. state, need to work in parallel to mediate and allow memory
      functioning, respectively.

PMID- 14584567
TI  - Acquisition, recall, and forgetting of verbal information in long-term memory by
      young, middle-aged, and elderly individuals.
AB  - Memory performance by four age groups (30-45 years, 46-60 years, 61-75 years, and
      76-90 years) was compared on a multi-trial verbal recall task with 20-minute and
      1-day delay free recall and recognition trials. The rate of acquisition across 5
      learning trials was similar for all ages except the youngest group whose
      performance was constrained by a ceiling effect. The level of acquisition
      achieved was less in the two oldest groups. Words gained across trials and words
      lost across trials made similar contributions to the shape of the learning curve
      for the acquisition trials. Subjective organization decreased with age, but
      remained strongly related to the number of words recalled during acquisition for
      all age groups. The two oldest age groups demonstrated significant declines in
      words recalled on the 20-minute and 1-day delay trials. A subset of the oldest
      group demonstrated more rapid forgetting at the 1-day delay when participants
      from all age conditions were matched on acquisition. Thus, many aspects of free
      recall were impaired with age, and variance measurement of recall showed greater
      inter-individual differences with increasing age. This increase in individual
      differences could reflect a single form of age-related memory impairment, or it
      could indicate that memory impairment in the elderly is due to multiple
      processes. The importance of testing across the life span and using tests that
      examine a variety of memory components and processes for establishing norms and
      clarifying age-related deficits are discussed.

PMID- 14584568
TI  - High prevalence of white matter hyperintensities in normal aging: relation to
      blood pressure and cognition.
AB  - The occurrence of cerebral white matter hyperintensities (WMHs), and their
      associations with blood pressure, episodic memory, and other cognitive tasks,
      were examined in a population-based sample of 123 individuals between 64 and 74
      years old. Magnetic Resonance Imaging (MRI) detected subcortical and
      periventricular hyperintensities in 90% and 67% of the cases, respectively.
      Subcortical WMHs were related to elevated diastolic blood pressure measured ten
      years earlier, and periventricular WMHs were related to elevated diastolic blood
      pressure measured five and ten years earlier. Subcortical hyperintensities were
      weakly associated with impaired motor speed, but this association was not
      significant. Periventricular WMHs had a negative effect on episodic memory,
      although the relation was not linear. Collectively, the notion that white matter
      hyperintensities impair cognitive function got weak support in this Swedish
      sample.

PMID- 14584569
TI  - On the involvement of prefrontal networks in cognitive ageing.
AB  - Normal ageing is associated with a wide variety of disturbances in the structure
      and function of the human brain. Recent neuroimaging studies suggest that the
      prefrontal cortex (PFC) is particularly vulnerable to the effects of ageing.
      These findings are compatible with the so-called 'frontal ageing hypothesis'
      which has been formulated on the basis of neuropsychological research on non
      pathological ageing. We will argue on the basis of recent structural and
      functional neuroimaging studies that this hypothesis needs to be refined,
      especially to acknowledge the possible relevance of a distinction between
      subregions within the PFC. In addition, findings with regard to a differential
      involvement of grey versus white matter suggest that both have to be considered
      in relation to age-related cognitive decline. Hence, neural networks and larger
      systems of interconnected brain regions and the functional activity in these
      circuits may be more important than specific cortical regions to explain age
      effects on cognitive functioning. Finally, it is important to consider individual
      variability due to sex differences and age-extrinsic biomedical factors in
      research which examines the relationship between brain structure or function and
      cognitive ageing.

PMID- 14584570
TI  - Memory in autism: review and synthesis.
AB  - Much research about memory in autism concerns the hypothesis that autism is
      similar to adult-onset amnesia. Initial support for the hypothesis came from post
      mortem studies of individuals with autism showing abnormalities in the
      hippocampus and related brain structures, as well as behavioral studies finding
      contrasts between intact cued recall and impaired free recall and recognition in
      autism. The hypothesis was later brought into question by the finding of intact
      performance in individuals with autism on explicit memory tasks typically
      impaired in adult-onset amnesia. The present paper proposes a possible
      reconciliation of these contradictory findings, suggesting that there is
      selective damage to the limbic-prefrontal episodic memory system, sparing the
      limbic-only perceptual representation system, and the semantic memory system.
      This view is consistent with other evidence for early selective damage to other
      systems involving cooperation between the limbic system and the medial prefrontal
      cortex in autism.

PMID- 14584571
TI  - Hebb, pandemonium and catastrophic hypermnesia: the hippocampus as a suppressor
      of inappropriate associations.
AB  - The hippocampus has been proposed as a key component of a "behavioural inhibition
      system". We explore the implications of this idea for the nature of associative
      memory--i.e. learning that is distinct from the moulding of response sequences by
      error correction and reinforcement. It leads to the view that all associative
      memory depends on purely Hebbian mechanisms. Memories involve acquisition of new
      goals not the strengthening of new stimulus-response links. Critically, memories
      will consist of affectively positive and affectively negative associations as
      well "purely cognitive" information. The hippocampus is seen as a supervisor that
      is normally "just checking" information about current available goals. When one
      available goal is pre-eminent there is no hippocampal output and the goal
      controls the response system. When two or more goals are similarly and highly
      primed there is conflict. This is detected by the hippocampus which sends output
      that increases the valence of affectively negative perceptions and so resolves
      the conflict by suppressing more aversive goals. Such conflict resolution occurs
      with innate as well as acquired goals and is fundamentally non-memorial. But, in
      memory paradigms, it can often act to suppress interference on the current trial
      and, through Hebbian association of the increase in negative affect, decrease the
      probability of interference on later trials and during consolidation. Both memory
      driven and innate behaviour is made hippocampal-dependent by innate and acquired
      conflicting tendencies and not the class of stimulus presented.

PMID- 14584572
TI  - Any questions?

PMID- 14584573
TI  - Attitude is all in the fight for the survival of rural practice.

PMID- 14584574
TI  - Salmonella serotypes present on a sample of Irish pig farms.
AB  - A survey of the prevalence of Salmonella species infection was conducted on 59
      Irish farrow-to-finish pig herds. Faecal samples were collected from the pens of
      first-stage weaners (growing pigs approximately three to 10 weeks of age), second
      stage weaners (approximately 10 to 17 weeks of age) and fatteners, and from the
      dry sow and farrowing sow houses. The prevalence of infection was estimated to
      within 5 per cent with a 95 per cent confidence interval. Thirty of the 59 herds
      were infected, 12 with Salmonella Typhimurium only, eight with Salmonella Derby
      only and seven with both S Typhimurium and S Derby; serotypes London, Livingstone
      and Infantis were each isolated from a single herd. Farms in Ireland are assigned
      to one of three infection categories on the basis of the antibody levels in
      samples of meat juice taken at slaughter. When a herd was classified as either
      positive or negative on the basis of the isolation of Salmonella from at least
      one faecal sample there was no association between the herd's category as
      determined by meat juice serology and the probability of the isolation of
      Salmonella from the faecal samples. However, there were differences in prevalence
      between pigs at different stages of production in herds of different categories.
      Farrowing sow houses in moderately infected (category 2) herds had significantly
      lower infection rates (P < or = 0.05) than other herd categories and other stages
      of production. Pigs from first-stage weaner pens in slightly infected (category
      1) herds were more likely to be infected with Salmonella than pigs at any other
      stage of production or category of herd.

PMID- 14584575
TI  - Use of nuclear scintigraphy with 99mTc-HMPAO-labelled leucocytes to assess small
      intestinal malabsorption in 17 horses.
AB  - The diagnostic and prognostic value of nuclear scintigraphy with technetium-99m
      labelled hexamethyl-propyleneamine oxime-labelled leucocytes was assessed in 17
      horses with weight loss due to gastrointestinal malabsorption by comparing the
      results with the results obtained from 13 normal control horses. Intestinal
      uptake of activity was detected in 12 of the 17 cases but none of the control
      horses. The technique was therefore specific for intestinal pathology, but failed
      to detect some horses that might have had intestinal pathology. No indications of
      the horses' specific pathology were obtained, and their prognosis or response to
      treatment could not be predicted.

PMID- 14584576
TI  - Changes in thermal threshold response in eight cats after administration of
      buprenorphine, butorphanol and morphine.
AB  - Thermal thresholds were measured in eight cats after the intramuscular
      administration of morphine (0.2 mg/kg), buprenorphine (0.01 mg/kg) or butorphanol
      (0.2 mg/kg), doses commonly used in clinical practice; 0.9 per cent saline (0.3
      ml) was injected as a control. Groups of six cats were used and each cat
      participated in at least two treatments, according to a randomised design. The
      investigator was blinded to the treatments. The thermal thresholds were measured
      with a testing device developed specifically for cats, and measurements were made
      before and five, 30, 45 and 60 minutes and two, four, six, 12 and 24 hours after
      the injections. There was no significant change in thermal threshold after the
      injection of saline. With butorphanol, the threshold was increased only at five
      minutes after the injection and was decreased two hours after the injection; with
      morphine it was increased from between four and six hours after the injection,
      and with buprenorphine it was increased from between four and 12 hours after the
      injection.

PMID- 14584577
TI  - Archival PCR-based diagnosis of Clostridium difficile in piglets.

PMID- 14584578
TI  - K-ras protooncogene mutations in feline pancreatic adenocarcinomas.

PMID- 14584579
TI  - Ureteroureterostomy after proximal ureteric injury during an ovariohysterectomy
      in a dog.

PMID- 14584580
TI  - Isolation of Streptococcus canis from a Japanese raccoon dog with fibrinous
      pleuropneumonia.

PMID- 14584581
TI  - Veterinary forensic science.

PMID- 14584582
TI  - Equine passports.

PMID- 14584583
TI  - Lay TB testing.

PMID- 14584584
TI  - Animals (Electric Shock Collars) Bill.

PMID- 14584585
TI  - Need for clinical audit.

PMID- 14584586
TI  - The PUF family of RNA-binding proteins: does evolutionarily conserved structure
      equal conserved function?
AB  - Drosophila Pumilio (Pum) protein is a founder member of a novel family of RNA
      binding proteins, known as the PUF family. The PUF proteins constitute an
      evolutionarily highly conserved family of proteins present from yeast to humans
      and plants, and are characterized by a highly conserved C-terminal RNA-binding
      domain, composed of eight tandem repeats. The conserved biochemical features and
      genetic function of PUF family members have emerged from studies of model
      organisms. PUF proteins bind to related sequence motifs in the 3' untranslated
      region (3'UTR) of specific target mRNAs and repress their translation.
      Frequently, PUF proteins function asymmetrically to create protein gradients,
      thus causing asymmetric cell division and regulating cell fate specification.
      Thus, it was recently proposed that the primordial role of PUF proteins is to
      sustain mitotic proliferation of stem cells. Here we review the evolution,
      conserved genetic and biochemical properties of PUF family of proteins, and
      discuss protein interactions, upstream regulators and downstream targets of PUF
      proteins. We also suggest that a conserved mechanism of PUF function extends to
      the newly described mammalian members of the PUF family (human PUM1 and PUM2, and
      mouse Pum1 and Pum2), that show extensive homology to Drosophila Pum, and could
      have an important role in cell development, fate specification and
      differentiation.

PMID- 14584587
TI  - IRS-1 regulation in health and disease.
AB  - The global incidence of diabetes is increasing at epidemic rates. Estimates
      suggest there are currently 150 million people with diabetes and this number is
      expected to double in the next 20 years. Type 2 diabetes accounts for 95% of all
      cases and is characterized in part by impaired sensitivity to insulin or 'insulin
      resistance'. Defects in the insulin signalling pathways underpin this resistance.
      In the current article we discuss the regulation of Insulin Receptor Substrate-1
      (IRS-1), a protein that plays a pivotal role in insulin signalling and whose
      function is impaired in subjects with insulin resistance. Coordination of IRS-1
      function is multi-faceted, involving phosphorylation of IRS-1 at multiple
      serine/threonine residues. This controls many aspects of IRS-1, including its
      interaction with the insulin receptor and subsequent tyrosine phosphorylation, as
      well as its subcellular distribution and targeting for degradation by the
      proteasome. Such tight control ensures appropriate transduction and attenuation
      of the insulin signal, thereby regulating insulin action in healthy individuals.
      Emerging evidence indicates that 'diabetogenic factors' associated with insulin
      resistance, such as TNFalpha and elevated circulating fatty acids, impact on
      insulin signalling at the level of IRS-1 serine/threonine phosphorylation. The
      expression and/or activity of several kinases, such as IkappaB kinase beta
      (IKKbeta) and salt-induced kinase 2 (SIK2), and the phosphorylation of IRS-1 at
      key sites, such as Ser307 and Ser789, are increased in states of insulin
      resistance. Identifying the pathways by which such factors activate these and
      other kinases, and defining the precise roles of specific serine/ threonine
      phosphorylation events in IRS-1 regulation, represent important goals which may
      eventually provide a rationale for therapeutic intervention.

PMID- 14584588
TI  - Redox reactions and electron transfer across the red cell membrane.
AB  - Plasma membrane electron transport systems appear to be ubiquitous. These systems
      are implicated in hormone signal transduction, cell growth and differentiation
      events as well as protection from oxidative stress. The red blood cell is
      constantly exposed to oxidative stress; protection against the reactive species
      generated during this process may be the main role of its membrane electron
      transport systems. Membrane redox activity has been studied for over three
      quarters of a century, and yet many questions remain regarding its identity and
      likely roles: are electron transfers by distinct and specific mechanisms; what
      are the physiological donors and acceptors; and how do these systems affect
      metabolism? Current evidence suggests that the human erythrocyte membrane
      contains a number of distinct electron transfer systems, some of which, at least,
      involve membrane proteins, and NADH or ascorbate as electron donors. The activity
      of these systems appears to be closely related to the metabolic state of the
      cell, suggesting that mediation of reducing equivalents across the plasma
      membrane allows redox buffering of each environment, intra- and extracellular, by
      the other. We have decided to study this from a new perspective, NMR spectroscopy
      the area of our own technical expertise, hence this review is slanted towards
      this more recent analysis.

PMID- 14584589
TI  - Hydrogenosomes, mitochondria and early eukaryotic evolution.
AB  - Available data suggest that unusual organelles called hydrogenosomes, that make
      ATP and hydrogen, and which are found in diverse anaerobic eukaryotes, were once
      mitochondria. The evolutionary origins of the enzymes used to make hydrogen,
      pyruvate:ferredoxin oxidoreductase (PFO) and hydrogenase, are unresolved, but it
      seems likely that both were present at an early stage of eukaryotic evolution.
      Once thought to be restricted to a few unusual anaerobes, these proteins are
      found in diverse eukaryotic cells, including our own, where they are targeted to
      different cell compartments. Organelles related to mitochondria and
      hydrogenosomes have now been found in species of anaerobic and parasitic protozoa
      that were previously thought to have separated from other eukaryotes before the
      mitochondrial endosymbiosis. Thus it is possible that all eukaryotes may
      eventually be shown to contain an organelle of mitochondrial ancestry, bearing
      testimony to the important role that the mitochondrial endosymbiosis has played
      in eukaryotic evolution. It remains to be seen if members of this family of
      organelles share a common function essential to the eukaryotic cell, that
      provides the underlying selection pressure for organelle retention under
      different living conditions.

PMID- 14584590
TI  - The Rhodococcus sp. cocaine esterase: a bacterial candidate for novel
      pharmacokinetic-based therapies for cocaine abuse.
AB  - Cocaine is a powerful central nervous stimulant and among the most abused of
      drugs. Despite decades of efforts, however, no effective pharmacological
      treatments are available against cocaine addiction or toxic effects. Classical
      receptor-antagonist therapeutic approaches have not yielded significant effects,
      although cocaine targets are well known, thus fostering development of
      alternative therapeutic strategies. Recent evidence indicates that a sensible
      approach for treatment of cocaine abuse could be to interfere with cocaine
      pharmacokinetics, i.e. by preventing the drug from reaching the receptors
      responsible for its biological effects. Administration of cocaine binding
      antibodies as well as catalytic antibodies and enzymes that hydrolyze cocaine
      represent potential alternative therapeutic approach(es). The discovery of the
      cocaine esterase from the strain MBI of the bacterium Rhodococcus sp. (cocE)
      could be a major breakthrough in this field; cocE hydrolyzes cocaine faster than
      any known cocaine esterase and catalytic antibody.

PMID- 14584591
TI  - Functional role of caspases in sphingosine-induced apoptosis in human hepatoma
      cells.
AB  - We have previously shown that sphingosine increased caspase-3 activity and
      induced apoptosis in human hepatoma cells. Our data also suggest that other
      caspases may be involved in sphingosine-triggered apoptosis. In order to clarify
      this issue, we used different approaches to study the functional role of several
      initiator or executioner caspases in apoptosis induced by sphingosine. Activation
      of procaspases-2, -7, and -8, was clearly demonstrated during sphingosine
      triggered apoptosis. Pretreatment with chemical inhibitors for caspase-7 and -8,
      attenuated apoptotic cell death induced by sphingosine. Conversely, pretreatment
      with specific caspase-2 inhibitor Z-VDVAD-FMK did not show any protective effect.
      In addition, enforced expression of constitutively activated AKT kinase which is
      known to inhibit apoptosis induced by sphingosine, potently suppressed activation
      of procaspases-7 and -8. In summary, these data suggest that in addition to
      caspases-3, caspase-7 and -8 are involved in the apoptosis induced by
      sphingosine.

PMID- 14584592
TI  - Effect of moderate acute exercise on expression of mRNA involved in the
      calcineurin signaling pathway in human skeletal muscle.
AB  - Calcineurin, a calcium-regulated protein phosphatase, activates gene expression
      specific to slow muscle fibers by dephosphorylating a family of the nuclear
      factor of activated T cells (NFAT), which cooperates with myocyte enhancer factor
      2 (MEF2) and AP-1. However, it remains unknown how acute exercise influences this
      signaling pathway and leads to the development of slow muscle fibers. In the
      present study, we investigated the effect of moderate acute exercise on mRNA
      expression of genes in the calcineurin signaling pathway in human skeletal
      muscle. Five healthy volunteers underwent 1 h bicycle ergometer at 50%VO2max, and
      vastus lateralis muscle biopsies were collected before and after exercise. Four
      hours after exercise, alterations in mRNA expression of NFAT 1-3 were observed
      with a wide variety among subjects, while c-fos mRNA was significantly induced in
      all subjects. By contrast, the expression of calcineurin, MEF2, and myocyte
      enriched calcineurin-interacting protein 1 (MCIP1) remained unchanged. These
      results suggest that even moderate acute exercise may change mRNA expression of
      genes in the calcineurin-signaling pathway.

PMID- 14584595
TI  - How I became a biochemist.

PMID- 14584593
TI  - Triggering of apoptosis is not sufficient to induce human immunodeficiency virus
      gene expression.
AB  - We examined whether there is any causative link between apoptosis and HIV gene
      expression elicited in response to ultraviolet light (UV) and ionizing radiation
      (IR). We found that both UV and IR activate HIV gene expression in human T
      lymphoblastoid 1G5 (HIVluc) cells, but with different kinetics and magnitudes.
      Treatment with either type of radiation resulted in increased apoptosis, which
      correlated closely with HIV gene expression. The involvement of caspases in the
      IR response was demonstrated by using zVAD-FMK and zDEVD-FMK caspase inhibitors;
      both apoptosis and HIV gene expression were inhibited to similar extent.
      Surprisingly, treatment of 1G5 cells with FAS antibody triggered apoptosis but
      did not increase HIV gene expression. A correlation between increased apoptosis
      and gene expression was also demonstrated in human carcinoma HIVcat/A549 cells
      with UV whereas IR triggered apoptosis but did not activate HIV gene expression.
      Most significantly, UV activation of HIV gene expression, and NF-kappa-B and p38
      MAP kinase, both important for efficient HIV gene expression, were not affected
      by treatment with the zVAD-FMK and zDEVD-FMK inhibitors. Treatment of HIVcat/A549
      cells with staurosporine or scrape-loading of cells with cytochrome c resulted in
      apoptosis but no increase in HIV gene expression. Altogether, a direct
      correlation exists between apoptosis and HIV gene expression in T-cells in
      response to both UV and IR but this is not the case in carcinoma cells.
      Triggering of apoptosis per se in either cell type does not necessarily result in
      increased HIV gene expression. Most importantly, the apoptotic and HIV gene
      expression responses elicited by UV are different to some extent and can be
      separated.

PMID- 14584594
TI  - Is there an answer? How did the idea of breeding rats for intrinsic aerobic
      running capacity come about?

PMID- 14584596
TI  - Effect of conjugated FA on feed intake, body composition, and liver FA in mice.
AB  - CLA is a generic term describing different isomers of linoleic acid with two
      conjugated double bonds. Various metabolic effects have been demonstrated
      following administration of CLA, including a change in body composition in
      animals. However, the effects of pure CLA isomers are not fully understood. In
      addition, conjugated octadecatrienoic acids such as calendic acid have not been
      extensively investigated. In this study, male and female ICR mice were fed pure
      CLA isomers (cis9,trans11 or trans10,cis12) or calendic acid
      (trans8,trans10,cis12) as their ethyl esters for 6 wk. Body protein content was
      significantly increased after feeding CLA isomers, either as pure isomers or as a
      mixture. Calendic acid significantly decreased body fat content in males. CLA
      (pure isomers or a mixture) significantly decreased body fat in both males and
      females, with the trans10,cis12 isomer being the most effective. The effect of
      the cis9,trans11 isomer was more pronounced in females than in males. It was
      concluded that the trans10,cis12 CLA isomer was mainly responsible for the
      decrease in fat content in mice, without a significant modification of feed
      efficiency, and that it was more effective than calendic acid.

PMID- 14584597
TI  - Recoveries of rat lymph FA after administration of specific structured 13C-TAG.
AB  - The potential of the specific structured TAG MLM [where M = caprylic acid (8:0)
      and L = linoleic acid (18:2n-6)] is the simultaneous delivery of energy and EFA.
      Compared with long-chain TAG (LLL), they may be more rapidly hydrolyzed and
      absorbed. This study examined the lymphatic recoveries of intragastrically
      administered L*L*L*, M*M*M*, ML*M, and ML*L* (where * = 13C-labeled FA) in rats.
      Lymph lipids were separated into lipid classes and analyzed by GC combustion
      isotope ratio MS. The recoveries of lymph TAG 18:2n-6 8 h after administration of
      L*L*L*, ML*M, and ML*L* were 38.6, 48.4, and 49.1%, respectively, whereas after
      24 h the recoveries were approximately 50% in all experimental groups. The
      exogenous contribution to lymph TAG 18:2n-6 was approximately 80 and 60% at
      maximum absorption of the specific structured TAG and L*L*L*, respectively, 3-6 h
      after administration. The tendency toward more rapid recovery of exogenous long
      chain FA following administration of specific structured TAG compared with long
      chain TAG was probably due to fast hydrolysis. The lymphatic recovery of 8:0 was
      2.2% 24 h after administration of M*M*M*. This minor lymphatic recovery of
      exogenous 8:0 was probably due to low stimulation of chylomicron formation. These
      results demonstrate tendencies toward faster lymphatic recovery of long-chain FA
      after administration of specific structured TAG compared with long-chain TAG.

PMID- 14584598
TI  - TG containing stearic acid, synthesized from coconut oil, exhibit lipidemic
      effects in rats similar to those of cocoa butter.
AB  - Lipase-catalyzed interesterification was used to prepare structured TG from
      coconut oil TG by partially replacing some of the atherogenic saturated FA with
      stearic acid, which is known to have a neutral effect on lipid levels in the
      body. The level of stearic acid was increased from 4% in the native coconut oil
      to 40% in the structured lipids, with most of the stearic acid being incorporated
      into the sn-1 and sn-3 positions of TG. When structured lipids were fed to rats
      at a 10% level for a period of 60 d, a 15% decrease in total cholesterol and a
      23% decrease in LDL cholesterol levels in the serum were observed when compared
      to those fed coconut oil. Similarly, the total and free cholesterol levels in the
      livers of the rats fed structured lipids were lowered by 31 and 36%,
      respectively, when compared to those fed coconut oil. The TG levels in the serum
      and in the liver showed decreases of 14 and 30%, respectively, in animals fed
      structured lipids. Rats fed cocoa butter and structured lipids having a similar
      amount of stearic acid had similar lipid levels in the serum and liver. These
      studies indicated that the atherogenic potential of coconut oil lipids can be
      reduced significantly by enriching them with stearic acid. This also changed the
      physical properties of coconut oil closer to those of cocoa butter as determined
      by DSC.

PMID- 14584599
TI  - Enzyme-resistant fractions of beans lowered serum cholesterol and increased
      sterol excretions and hepatic mRNA levels in rats.
AB  - Feeding rats beans with resistant starch reduces their serum cholesterol
      concentration; however, the mechanism by which this occurs is not fully
      understood. We examined the effects of enzyme-resistant fractions of adzuki
      (Vigna angularis) and tebou (Phaseolus vulgaris, var.) beans on serum cholesterol
      and hepatic mRNA in rats. Rats were fed a cholesterol-free diet with 50 g of
      cellulose powder (CP)/kg, 50 g of an enzyme-resistant fraction of adzuki starch
      (AS)/kg, or 50 g of an enzyme-resistant fraction of tebou starch (TS)/kg diet for
      4 wk. There were no significant differences in body weight, liver weight, and
      cecum contents among the groups, nor was there a significant difference in food
      intake among the groups. The levels of serum total cholesterol, VLDL +
      intermediate density lipoprotein + LDL-cholesterol, and HDL cholesterol in the AS
      and TS groups were significantly (P < 0.05) lower than in the CP group throughout
      the feeding period. Total hepatic cholesterol in the CP group was significantly
      (P < 0.05) lower than in the AS and TS groups, fecal cholesterol excretion in the
      TS group was significantly (P < 0.05) greater than in the CP and AS groups, and
      the fecal total bile acid concentrations in the AS and TS groups were
      significantly (P < 0.05) higher than in the CP group. Cecal acetate, propionate,
      and n-butyrate concentrations in the AS and TS groups were significantly (P <
      0.05) higher than in the CP group. The level of hepatic scavenger receptor class
      B1 (SR-B1) mRNA in the TS group was significantly (P < 0.05) higher than in the
      CP group, and the levels of hepatic cholesterol 7alpha-hydroxylase mRNA in the AS
      and TS groups were significantly (P < 0.05) higher than in the CP group. These
      results suggest that AS and TS have a serum cholesterol-lowering function due to
      the enhanced levels of hepatic SR-B1 and cholesterol 7alpha-hydroxylase mRNA.

PMID- 14584600
TI  - Tissue deposition of n-3 FA pathway intermediates in the synthesis of DHA in
      rainbow trout (Oncorhynchus mykiss).
AB  - The tissue distribution of newly synthesized 22:6n-3 and intermediate PUFA was
      examined in rainbow trout to further our understanding of the metabolism of this
      EFA in fish. Rainbow trout were fed a pulse of deuterated linolenic acid (D5
      17,17,18,18,18-18:3n-3), and the tissue distribution of deuterated anabolites was
      determined at intervals up to 35 d post-dose by GC-negative chemical ionization
      MS of the pentafluorobenzyl derivatives. D5-22:6n-3 was the major deuterated FA
      in liver and cecal mucosa 2 and 5 d post-dose. All the n-3 FA pathway
      intermediates were found in liver, cecal mucosa, and blood including D5-24:5n-3
      and D5-24:6n-3. Brain and eyes also contained the full suite of intermediate
      deuterated FA, but with a different profile from liver when analyzed over a
      longer time course up to 35 d. D5-20:5n-3 was the major component in brain up to
      7 d, after which D5-22:6n-3 became predominant, but D5-22:5n-3 constituted ca.
      20% of FA throughout the time period. The pattern in eyes was similar but less
      pronounced. In visceral adipose tissue there was a much greater accumulation of
      the initial substrate, D5-18:3n-3, with D5-18:4n-3 and D5-22:6n-3 the predominant
      deuterated FA at all time points. There was a similar though less pronounced
      trend in eye socket adipose tissue. The C24 PUFA were not detected in visceral
      fat and barely detected in eye socket fat. The results show that the kinetics of
      accumulation and depletion of the various n-3 PUFA differ between tissues. The
      presence of pathway intermediate FA provides evidence that liver and ceca possess
      the full metabolic pathway for synthesis of 22:6n-3, whereas brain and eyes are
      less active, with an accumulation of pentaene intermediate FA, and adipose tissue
      is inactive.

PMID- 14584601
TI  - Solubilization of carotenoids from carrot juice and spinach in lipid phases: I.
      Modeling the gastric lumen.
AB  - Our understanding of the factors determining the bioavailability of carotenoids
      from fruits and vegetables is poor. The apolar nature of carotenoids precludes
      their simple diffusion from the food structure to the absorption site at the
      enterocyte. Therefore, there is interest in the potential pathways for
      solubilization in the gut before absorption. We have studied the transfer of
      carotenoids from carrot juice and homogenized spinach into lipid phases that
      mimic the intestinal lumen at the start of digestion. In this paper we report on
      their transfer into olive oil under conditions pertaining to the gastric
      environment. A comparison between preparations of raw spinach and of carrot, in
      which the intact cells have been largely broken, suggests that the membrane-bound
      carotenoids of spinach are more resistant to transfer than the crystalline
      carotenoids of carrot. Lowering the pH and pepsin treatment enhance the transfer
      from raw vegetables. The process of blanching and freezing spinach destroys the
      chloroplast ultrastructure and leads to (i) a substantial increase in transfer of
      the carotenoids to oil and (ii) an attenuation or reversal of the enhancement of
      transfer seen with reduced pH or with pepsin treatment. Similar effects are seen
      after blanching carrot juice. Our results show that removal of soluble protein
      and denaturation of membrane proteins enhances the partition of carotenoids into
      oil. For both vegetables there is no evidence of preference in the extent of
      transfer of one carotenoid over another. This suggests that partitioning into oil
      under gastric conditions is not the stage of digestion that could lead to
      differences in carotenoid bioavailability.

PMID- 14584602
TI  - Solubilization of carotenoids from carrot juice and spinach in lipid phases: II.
      Modeling the duodenal environment.
AB  - We have been investigating the factors determining the bioavailability of
      carotenoids from vegetables. The previous paper [Rich, G.T., Bailey, A.L.,
      Faulks, R.M., Parker, M.L., Wickham, M.S.J., and Fillery-Travis, A. (2003)
      Solubilization of Carotenoids from Carrot Juice and Spinach in Lipid Phases: I.
      Modeling the Gastric Lumen, Lipids 38, 933-945] modeled the gastric lumen and
      studied the solubilization pathway of carotenes and lutein from carrot juice and
      homogenized spinach to oil. Using the same vegetable preparations, we have
      extended our investigations to solubilization pathways potentially available in
      the duodenum and looked at the ease of solubilization of carotenes and lutein
      within simplified lipid micellar and oil phases present within the duodenum
      during digestion. Micellar solubility of raw spinach carotenoids was low and was
      enhanced by freezing, which involved a blanching step. The efficiency of
      solubilization of carotenoids in glycodeoxycholate micelles decreased in the
      order lutein(carrot) > lutein(blanched-frozen spinach) > carotene(blanched-frozen
      spinach) > carotene(carrot). Frozen spinach carotenoids were less soluble in
      simple micelles of taurocholate than of glycodeoxycholate. The results comparing
      the solubility of the carotenoids in mixed micelles (bile salt with lecithin)
      with simple bile salt micelles are explained by the relative stability of the
      carotenoid in the organelle compared to that in the micelle. The latter is
      largely determined by the polarity of the micelle. Below their critical micelle
      concentration (CMC), bile salts inhibit transfer of carotenoids from tissue to a
      lipid oil phase. Above their CMC, the bile salts that solubilize a carotenoid can
      provide an additional route to the oil from the tissue for that carotenoid by
      virtue of the equilibrium between micellar phases and the interfacial pathway.
      Mixed micellar phases inhibit transfer of both carotenoids from the tissue to the
      oil phase, thereby minimizing this futile pathway.

PMID- 14584603
TI  - Peroxisome proliferator-activated receptor alpha is not the exclusive mediator of
      the effects of dietary cyclic FA in mice.
AB  - Cyclic FA monomers (CFAM) formed during heating of alpha-linolenic acid have been
      reported to interfere in hepatic metabolism in a putatively peroxisome
      proliferator-activated receptor alpha (PPARalpha)-dependent manner. In the
      present work, CFAM (0.5% of the diet) were administered for 3 wk to wild-type and
      PPARalpha-null mice of both genders to elucidate the role of PPARalpha in
      mediating the effects of CFAM on the activity of acyl-CoA oxidase (ACO) and omega
      laurate hydroxylase (CYP4A), the regulation of which is known to be dependent on
      the PPARalpha. Dietary CFAM enhanced CYP4A activity threefold in male and female
      wild-type mice. This effect was abolished in PPARalpha-null mice. A twofold
      induction of ACO activity was found in wild-type female mice fed CFAM; however,
      no effect was seen in males. In wild-type animals, (omega-1)-laurate hydroxylase
      (CYP2E1) activity, the expression of which has not been shown to be PPARalpha
      dependent, was not affected by the CFAM diet. In contrast, stearoyl-CoA
      desaturase activity was reduced in wild-type mice. CFAM feeding reduced the
      activities of ACO, CYP2E1, and stearoyl-CoA desaturase and caused accumulation of
      lipids in the livers of female PPARalpha-null mice. These data show that CFAM
      apparently activate gene expression via the PPARalpha and have profound effects
      on lipid homeostasis, exacerbating the disturbances preexisting in mice lacking
      functional PPARalpha. Although the data emphasize the importance of PPARalpha in
      the metabolism of the CFAM, these results show that PPARalpha is not the
      exclusive mediator of the effects of CFAM in lipid metabolism in mice.

PMID- 14584605
TI  - Electrophile tocopheryl quinones in apoptosis and mutagenesis: thermochemolysis
      of thiol adducts with proteins and in cells.
AB  - Electrophile tocopheryl quinones from the phenolic antioxidants gamma-tocopherol
      and delta-tocopherol form Michael adducts with the thiol nucleophile glutathione.
      These tocopheryl quinones are involved in cytotoxicity, apoptosis, and
      mutagenesis, and their biologic properties are associated with the depletion of
      intracellular thiols. We now show that both proteins and tissues treated with the
      electrophile gamma-tocopheryl quinone (gamma-TQ) form thiol adducts. The
      monoglutathion-S-yl derivative of gamma-TQ was subjected to thermochemolysis with
      the strong methylating base tetramethylammonium hydroxide. GC/MS showed four
      signature peaks and a fragmentation pattern characteristic of the thiol adduct.
      Similarly, pure monoglutathion-S-yl and diglutathion-S-yl derivatives of delta-TQ
      were subjected to thermochemolysis, and GC/MS showed characteristic fragmentation
      patterns for thiol adducts. The four signature peaks were identified when pure
      proteins with accessible thiol groups (hemoglobin and histone), FBS, and tissue
      culture medium and cell preparations were treated with gamma-TQ. Signature peaks
      in both complete medium and washed cells showed the presence of both soluble and
      insoluble thiol adducts. The effective or free arylating electrophile
      concentration in complete medium should always be evaluated in tissue culture
      studies. gamma-TQ is a mutagen but not a genotoxin; therefore, the histone adduct
      may be a previously unrecognized histone modification involved in chromatin
      dynamics leading to mutagenesis.

PMID- 14584604
TI  - Stimulation of rat liver mitochondrial sn-glycerol-3-phosphate acyltransferase by
      polymyxin B via enhanced extraction of lysophosphatidic acid.
AB  - The purpose of this investigation was to determine how polymyxin B stimulates the
      activity of mitochondrial glycerophosphate acyltransferase. Polymyxin B did not
      change the integrity of the mitochondrial outer membrane as judged by testing the
      latency (>80%) of cytochrome oxidase activity. The stimulation totally
      disappeared when polymyxin B-treated mitochondria were washed. The FA side chain
      in polymyxin B was unnecessary for stimulation, as the nonapeptide was as
      effective as the whole antibiotic. The stimulation by polymyxin B or the
      nonapeptide was observed only in the presence of BSA. Cytochrome c, when added to
      the incubation medium instead of albumin, did not stimulate the mitochondrial
      enzyme, but did produce a stimulatory effect of polymyxin B on the mitochondrial
      acyltransferase. As reported earlier for the bacterial and microsomal
      acyltransferase, other polycationic compounds such as spermine and spermidine
      stimulated mitochondrial glycerophosphate acyltransferase. The stimulation of the
      mitochondrial acyltransferase by spermine and spermidine also occurred only in
      the presence of BSA. The analysis of the products of esterification demonstrated
      the presence of more lysophosphatidic acid (LPA) in the polymyxin B- and
      polyamine-stimulated assays in comparison to their respective control.
      Furthermore, in comparison to the albumin-treated control, there was 60% more LPA
      present in the assay supernatant fractions of polymyxin B-treated samples. Our
      results suggest that polymyxin B stimulates the mitochondrial glycerophosphate
      acyltransferase activity by enhancing the extraction of more LPA from the
      mitochondria to the supernatant fraction.

PMID- 14584606
TI  - Divergent pattern of polyisoprenoid alcohols in the tissues of Coluria geoides: a
      new electrospray ionization MS approach.
AB  - Polyisoprenoid alcohols of the plant Coluria geoides were isolated and analyzed
      by HPLC with UV detection to determine the nature of the polyprenol and dolichol
      mixture in the organs studied. In roots, a family of dolichols (Dol-15 to Dol-23,
      with Dol-16 dominating, where Dol-n is dolichol composed of n isoprene units) was
      accompanied by traces of polyprenols of similar chain lengths, whereas in hairy
      roots grown in vitro, identical patterns with a slightly broader chain-length
      range were found. Conversely, in leaves and seeds polyprenols were the dominant
      form, and their pattern was shifted toward longer chains (maximal content of Pren
      19, where Pren-n is polyprenol composed of n isoprene units). Interestingly, the
      pattern of dolichols in seeds and leaves (in which Dol-17 dominated) was similar
      to that found in roots. Structures of the dolichols and polyprenols isolated were
      confirmed by the application of a new HPLC/electrospray ionization-MS method,
      which also offers a much higher sensitivity in detection of these compounds
      compared to a UV detector. The highest sensitivity was obtained when the [M +
      Na]+ ions of polyprenols and dolichols were recorded in the selected ion
      monitoring mode and a small amount of sodium acetate solution was added post
      column to enhance the formation of these ions in an electrospray ion source.

PMID- 14584607
TI  - Localization of clavulones, prostanoids with antitumor activity, within the
      Okinawan soft coral Clavularia viridis (Alcyonacea, Clavulariidae): preparation
      of a high-purity Symbiodinium fraction using a protease and a detergent.
AB  - To investigate the localization of clavulones (CV), prostanoids with antitumor
      activity, in the Okinawan soft coral Clavularia viridis, we developed a method
      for the isolation of Symbiodinium cells from the coral, i.e., treatment of a
      coral homogenate with a protease, pronase E, and a detergent, Nonidet P-40. The
      conditions for the treatment were optimized by monitoring the morphology
      microscopically and the amount of chlorophyll in the Symbiodinium fraction (SymF)
      optically. To evaluate the purity of SymF and a Symbiodinium-free coral fraction
      (CorF), we analyzed them for proteins and lipids using cultivated Symbiodinium as
      a reference. TLC of lipids revealed that SymF contained a greater amount of
      glycolipids, whereas CorF comprised mostly phospholipids. SDS-PAGE of proteins in
      SymF and CorF revealed their distinct profiles. Thus, we could obtain each
      fraction with high purity; we reached the conclusion that CV and arachidonic
      acid, their possible precursor, are localized exclusively in the insoluble
      fraction of host coral cells.

PMID- 14584608
TI  - Light-scattering detection of phospholipids resolved by HPLC.
AB  - An improved method for the analysis of phospholipids by normal-phase HPLC is
      described. Addition of methanol and acetonitrile to a gradient based on 2
      propanol/hexane/water promoted a rapid separation of major classes of bovine
      surfactant phospholipids (PL) by using a conventional silica column. The use of
      an ELSD permitted an accurate analysis of a mixture of PL. Calibration curves
      were linear within the range of 5-40 microg with detection limits below 1 microg
      for PE and PC, and CV ranged from 0.6 to 9.6%. PL present in surfactant
      homogenates were separated by a solid-phase extraction (SPE) procedure before
      HPLC analysis. This methodology gave a recovery of 95% and combined SPE-HPLC and
      quantification of biological PL within a 30-min run. The use of ELSD detection of
      the eluted compounds was precise, linear, and sensitive.

PMID- 14584609
TI  - The size of cagA based on repeat sequence has the responsibility of the location
      of Helicobacter pylori in the gastric mucus and the degree of gastric mucosal
      inflammation.
AB  - The aim of this study was to examine whether there is a relationship between cagA
      size of Japanese Helicobacter pylori strains and the location of these strains in
      the mucous layer, the degree of gastric inflammation and acid survival. Upper
      gastrointestinal endoscopies were done to 144 patients with dyspeptic symptom
      with informed consent, sera, biopsy specimens and H. pylori strains were
      obtained, and gastric histology and susceptibility to pH 3 of the strains were
      evaluated. To determine cagA size of Japanese strains using PCR, cagA of strain
      CPY3401 was sequenced. 74 H. pylori samples (72 cagA+) were obtained from the
      body and 56 samples (56 cagA +) obtained from the antrum. cagA size of 72 H.
      pylori strains from the body was mainly classified into 3 groups (short (48),
      middle (8), long (9), and others (7)) by PCR and all of that of 56 strains from
      the antrum except 2 was short. The size of cagA of isolated strains from the body
      is associated with enhanced gastritis, acid survival, and the location in the
      mucus. The long size cagA of which strain is acid sensitive, may be a strong
      selective pressure on strain that colonizes close to the host, which enhanced
      gastritis.

PMID- 14584610
TI  - Improvements of PCR-based identification targeting the DNA topoisomerase II gene
      to determine major species of the opportunistic fungi Candida and Aspergillus
      fumigatus.
AB  - For the simple and rapid detection/identification of major pathogenic fungal
      species such as Candida albicans, C. tropicalis, C. parapsilosis, C. glabrata and
      Aspergillus fumigatus, common primers for these species and specific primers for
      each species, designed on the basis on the genomic nucleotide sequences of the
      DNA topoisomerase II genes, were prepared and tested for their specificities in
      PCR amplifications. Twelve specific primers were pooled and designated PsVI.
      Genomic DNAs were amplified by the common primer pair, and followed by PCR
      amplification using PsVI. Using PsVI, six unique DNA fragments, all of which
      corresponded to a Candida or A. fumigatus species, were specifically and
      acceptably amplified from each template DNA even in the presence of other DNAs.
      Similarly, the results of identification of clinical samples based on the PCR
      amplification coincided with those of conventional identification techniques. The
      sensitivities of the direct PCR and the nested PCR using PsVI were found to be
      1,000 and 50 yeast cells, respectively.

PMID- 14584611
TI  - Monoclonal antibody #3-9-16 recognizes one of the two isoforms of rabies virus
      matrix protein that exposes its N-terminus on the virion surface.
AB  - We investigated behaviors of the rabies virus matrix (M) protein using a
      monoclonal antibody (mAb), #3-9-16, that recognized a linear epitope located at
      the N-terminus of the protein. Based on the reactivity with this mAb, M proteins
      could be divided into at least two isoforms; an ordinary major form (Malpha)
      whose 3-9-16 epitope is hidden, and an N-terminal-exposed epitope-positive form
      (Mbeta). The Mbeta protein accounted for about 25-30% of the total M proteins in
      the virion, while its content in the cell ranged from 10 to 15% of total M
      protein. Fluorescent antibody (FA) staining showed that the Mbeta antigen
      distributed in the Golgi area where the colocalized viral glycoprotein antigen
      was also detected. Mbeta antigen was shown to be exposed on the surface of
      infected cells by both immunoprecipitation and FA staining with the mAb, whereby
      the cells might have become sensitive to the mAb-dependent complement-mediated
      cytolysis. Similarly, the Mbeta antigen was shown to be exposed on the virion
      surface, and the infectivity of the virus was destroyed by the mAb in the
      presence of a complement. Together with these results, we think that the M
      protein molecule takes either of two conformations, one (Mbeta) of which exposes
      the 3-9-16 epitope located in the N-terminal region of the M protein, that are
      also exposed on the surface of the virion and infected cells, whereby it might
      play a certain important role(s) in the virus replication process differently
      from the other form (Malpha), probably through its intimate association with the
      Golgi area and/or the cell membrane.

PMID- 14584612
TI  - Genetic characterization of rabies field isolates from Thailand.
AB  - We sequenced 512 nucleotides in two variable regions of the N gene of 23 rabies
      isolates from the northeastern part of Thailand by direct sequencing of PCR
      amplified products. The sequencing data revealed two new lineages in these rabies
      isolates. Based on the results of this study together with the findings of our
      earlier study, the rabies isolates in Thailand were divided into two genogroups,
      designated as T1 and T2, which were predominantly localized in the northern and
      northeastern areas, respectively. Each of these two genogroups consisted of four
      lineages. There was a correlation between these eight lineages and the
      geographical origins of the isolates. Two lineages belonging to the T2 genogroup
      from the northeastern area of Thailand were newly identified in this study. The
      isolates in both genogroups were also prevalent in the central area of Thailand.
      Each lineage in the T1 and T2 genogroups was found independently in dogs in the
      upper and lower southern areas of Thailand, respectively. These genetic data and
      the historical background suggest that rabies viruses belonging to the T2
      genogroups were prevalent many years ago in the central and northeastern areas of
      Thailand and were later transferred to the lower southern parts of Thailand.

PMID- 14584613
TI  - Antigenic analysis of nonstructural protein (NSP) 4 of group A avian rotavirus
      strain PO-13.
AB  - In order to analyze the antigenic structure of nonstructural protein (NSP) 4 of
      group A avian rotavirus strain PO-13, 25 monoclonal antibodies (MAbs) against
      NSP4 expressed in Escherichia coli were produced. All MAbs reacted with NSP4 on
      Western blotting, indicating that they recognized sequential epitopes. To
      determine the antigenic sites (ASs) recognized by the produced MAbs, seven
      truncated NSP4s were expressed in E. coli. Western blotting analysis showed that
      there are at least four major ASs on PO-13 NSP4, designated as AS I located in
      amino acids (aa) 151 to 169, AS II (aa 136 to 150), AS III (aa 112 to 133) and AS
      IV (aa 1 to 24). Two MAbs reacted exclusively with AS III encompassing the region
      that has been reported to be an enterotoxin domain. MAbs against ASs II, III and
      IV reacted with all avian rotaviruses tested by indirect immunofluorescent
      antibody assays. MAbs against AS I reacted with turkey strains, Ty-1 and Ty-3,
      but not with a chicken strain, Ch-1. Nine of 11 MAbs against AS II cross-reacted
      with NSP4 of mammalian rotavirus strains with different NSP4 genotypes. These
      results suggest that AS II on NSP4 is widely conserved among a variety of
      rotaviruses.

PMID- 14584614
TI  - Gamma interferon-induced nitric oxide production in mouse CD5+ B1-like cell line
      and its association with apoptotic cell death.
AB  - The in vitro effect of gamma interferon (IFN-gamma) on nitric oxide (NO)
      production in a mouse CD5+ B1-like cell line, TH2.52, was studied. The TH2.52
      cell line is the hybridoma line between mouse B lymphoma line and mouse splenic B
      cells and expresses a series of B1 markers. IFN-gamma induced a marked NO
      production in TH2.52 cells through the expression of an inducible type of NO
      synthase (iNOS). IFN-gamma-induced NO production was triggered by the Janus
      tyrosine kinase (JAK)/signal transducer and activator of transcription (STAT)
      pathway since it was inhibited by AG490, a JAK2 inhibitor. The growth of TH2.52
      cells significantly was inhibited in the presence of IFN-gamma. A significant
      number of cells underwent apoptotic cell death, accompanied by the DNA
      fragmentation, annexin V binding, and caspase 3 activation. N(G)-monomethyl-L
      arginine, an iNOS inhibitor, prevented IFN-gamma-induced cell death. Therefore,
      IFN-gamma-induced NO production was possible in causing cell death in TH2.52
      cells. Further, IFN-gamma-induced NO production and cell death significantly were
      prevented by interleukin-4, a representative Th2 cytokine. The immunological
      significance of IFN-gamma-induced NO production in a mouse B1-like cell line is
      discussed.

PMID- 14584615
TI  - The inhibitory effect of essential oils on herpes simplex virus type-1
      replication in vitro.
AB  - The antiviral effect of 12 essential oils on herpes simplex virus type-1 (HSV-1)
      replication was examined in vitro. The replication ability of HSV-1 was
      suppressed by incubation of HSV-1 with 1% essential oils at 4 C for 24 hr.
      Especially, lemongrass completely inhibited the viral replication even at a
      concentration of 0.1%, and its antiviral activity was dependent on the
      concentrations of the essential oil. When Vero cells were treated with the
      essential oil before or after viral adsorption, no antiviral activity was found,
      which suggests that the antiviral activity of essential oils including lemongrass
      may be due to the direct interaction with virions.

PMID- 14584616
TI  - Herpes simplex virus UL14 protein blocks apoptosis.
AB  - We report that an HSV-2 UL14 protein expressing cell line (14/HEp-2) was more
      resistant to apoptosis induced by osmotic shock and certain drugs than its
      parental cell line. Furthermore, HSV-1 UL14 protein deletion virus (UL14D) showed
      weaker inhibition of apoptosis compared to the rescued virus UL14R. The protein's
      anti-apoptotic function may derive from its heat shock protein-like properties.

PMID- 14584617
TI  - Terminological problems in information retrieval.
AB  - This is the first in the series of the papers on an application of the systems
      analytic approach to evaluation of information retrieval (IR). At the beginning,
      the importance of consistent terminology in information retrieval is discussed,
      and different definitions of "information retrieval" and "IR system" are
      presented. The importance of identifying boundaries of the IR system for
      clarifying terminological differences is discussed. The terminological problems
      in IR are summarized, and some of the existing approaches to their solution are
      identified. A historical overview of IR research is presented in order to explain
      the existing terminological differences and to create a common basis for a
      discussion of evaluation approaches to IR.

PMID- 14584618
TI  - Current status of the evaluation of information retrieval.
AB  - This is the second in the series of the articles on an application of the systems
      analytic approach to evaluation of information retrieval (IR). In the previous
      article a historical overview of IR was presented and existing terminological
      problems associated with IR were identified and discussed. In the presented
      article the current status of IR evaluation is summarized, and different
      evaluation approaches are discussed. The Cranfield evaluation model and the most
      often used relevance-based measures of recall and precision are explained, and
      their problems are presented. Possible evaluation alternatives to the Cranfield
      model are discussed, and the case for a systems analytic approach to IR is
      summarized.

PMID- 14584619
TI  - Measuring disparities in information capture timeliness across healthcare
      settings: effects on data quality.
AB  - The emergence of evidence-based medicine in the United States has created an
      industry-wide environment where the quality of data maintained by healthcare
      organizations is becoming a critical factor in the delivery of medical care. Such
      a transition necessitates a corresponding need for consistent data collection and
      maintenance methods. In this study results of a national survey of health
      information managers were used to assess prevalence of a standard data quality
      practice, the adoption of policies related to timeliness of data capture.
      Findings from this survey show that, on a national level, only a slight majority
      of respondents indicated adoption of timeliness policies. About 61% of
      respondents indicate they have policies and procedures addressing data
      timeliness, although persistent patterns of nonadoption were found. We examine
      how the timeliness of data collection might serve as part of an overall data
      collection strategy that managers can employ to improve the quality of their
      information.

PMID- 14584620
TI  - Regional variation in medical classification agreement: benchmarking the coding
      gap.
AB  - The growing use of classification and coding of patient data in medical
      information systems has resulted in increased dependence on the accuracy of
      coding practices. Information maintained on systems must be trusted by both
      providers and managers in order to serve as a viable tool for the delivery of
      healthcare in an evidence-based environment. A national survey of health
      information managers was employed here to assess observed levels of coder
      agreement with physician code selections used in classifying patient data.
      Findings from this survey suggest that, on a national level, the quality of coded
      data may suffer as a result of disagreement or inconsistent coding within
      healthcare provider organizations, in an era where physicians are increasingly
      called upon to enter and classify patient data via computerized medical records.
      Nineteen percent of respondents report that coder-physician classification
      disagreement occurred on more than 5% of all patient encounters. In some cases
      disagreement occurs in 20% or more instances of code selection. This phenomenon
      occurred to varying degrees across regions and market areas, suggesting a
      confounding influence when coded data is aggregated for comparative purposes. In
      an evidence-based healthcare environment, coded data often serves as a
      representation of clinical performance. Given the increasing complexity of
      medical information classification systems, reliance on such data may pose a risk
      for both practitioners and managers without consistent agreement on coding
      practices and procedures.

PMID- 14584621
TI  - Evaluation of performance of dental providers on posterior restorations: does
      experience matter? A data envelopment analysis (DEA) approach.
AB  - The purpose of this study is to discern what factors affect the longevity of
      amalgam and of composite restorations by dentists who perform posterior
      restorations. Data are obtained from the Washington Dental Service and contain
      1.5 million patient encounters representing visits to 23,000 providers from
      January 1993 through 31 December 1999. Analysis of provider performance is
      estimated through Data Envelopment Analysis. The principal finding is that the
      most efficient dentists produce posterior restorations that survive almost 5
      months (4.6 months) longer than those by inefficient providers (chi2 = 18.98, p <
      0.0001). The findings suggest that there is no difference in restoration
      longevity between amalgam and composite restorations when the restoration is
      performed by efficient provider.

PMID- 14584622
TI  - Neurofuzzy classification of the effect of diabetes mellitus on carotid artery.
AB  - Here, we present a new clasification system for the effects of diabetes mellitus
      (DM) on carotid artery by using neurofuzzy system. Blood flow hemodynamics were
      obtained from 118 carotid arteries of 59 patients with DM by using 7.5 MHz
      transducer and Doppler-M unit. Vmax = peak systole, Vmin = end diastole,
      resistive index (RI), and pulsatile index (PI) were measured with the use of
      Doppler sonography. These values were applied to neurofuzzy system using NEFCLASS
      model. With the increase of epoch from 200 to 500 and pruning of fuzzy rules, our
      classification system was found to be successful in 85% of the cases. In 100 of
      118 patients the classificitaion system was found to be correct. Our findings
      suggest that with the application of Doppler signal parameters from carotid
      arteries to neurofuzzy system may produce a new and reliable classification
      system for diagnosing diameter stenosis.

PMID- 14584623
TI  - A theory for classification of health care organizations in the new economy.
AB  - Most of the available studies into information technology (IT) have been limited
      to investigating specific issues, such as how IT can support decision makers
      distributing the information throughout health care organization, or how
      technology impacts organizational performance. In this study, for use in the
      planning of information system development projects, a theoretical model for the
      classification of health care organizations is proposed. We try to reflect the
      development in the contemporary digital economy by theoretically classifying
      health care organizations into three types, namely traditional, developing, and
      flexible. We describe traditional health care organizations as organizations with
      a centralized system for management and control. In developing health care
      organizations, IT is spread over the horizontal dimension and is used for
      coordinating the different parties throughout the organization. Finally, flexible
      health care organizations are those which work actively with the design of new
      health care organizational structure while they are designing the information
      system.

PMID- 14584624
TI  - Sphincter muscle stimulator to be used before treating anal atresia.
AB  - Closed rectum is a very frequently encountered anomaly of the newborns in our
      university hospital. Before making a rectal opening, the anorectal sphincter
      muscle needs to be stimulated to prevent any damage to the muscle itself In this
      study, we have designed a stimulator that provides reasonably constant output
      current depending on the physiological impedance of the rectal area. The current
      amplitude can be set between 20 and 250 mA. Stimulation pulses are adjusted for
      duration of 230 micros and can be obtained at a repetition period between 1.75
      and 20 ms. Fifteen patients in the Pediatric Surgery Department of Erciyes
      University Hospital were subjected to our stimulation tests. On average, about
      140 mA was enough to stimulate the muscle when probes were applied over the skin.
      On the other hand, with the placement of probes beneath the skin, stimulation was
      obtained for pulse amplitude of 40 mA.

PMID- 14584625
TI  - A multiagent architecture for developing medical information retrieval agents.
AB  - Information that is available on the world wide web (WWW) is already more vast
      than can be comprehensibly studied by individuals and this quantity is increasing
      at a staggering pace. The quality of service delivered by physicians is dependent
      on the availability of current information. The agent paradigm offers a means for
      enabling physicians to filter information and retrieve only information that is
      relevant to current patient treatments. As with many specialized domains, agent
      based information retrieval in medical domains must satisfy several domain
      dependent constraints. A multiple agent architecture is developed and described
      in detail to efficiently provide agent-based information retrieval from the WWW
      and other explicit information resources. A simulation of the proposed multiple
      agent architecture shows a 97% decrease in information overload and an 85%
      increase in information relevancy over existing meta-search tools (with even
      larger gains over standard search engines).

PMID- 14584627
TI  - Acute psychophysiological arousal and posttraumatic stress disorder: a two-year
      prospective study.
AB  - This study investigated the role of acute arousal in the development of
      posttraumatic stress disorder (PTSD). Hospitalized motor vehicle accident
      survivors (n = 146) were assessed for acute stress disorder (ASD) within 1 month
      of the trauma, 6 months later, and reassessed for PTSD 2 years posttrauma (n =
      87). Heart rates (HR) were assessed on the day of hospital discharge.
      Participants who had PTSD 2 years posttrauma had higher HR at hospital discharge
      than those without PTSD. A diagnosis of ASD or a resting HR of 95 beats per
      minute had moderate sensitivity (74%) and specificity (91%) in predicting PTSD.
      These findings suggest that caution is required in using acute HR as a predictor
      of longer-term PTSD following trauma.

PMID- 14584626
TI  - Co-twin control study of relationships among combat exposure, combat-related
      PTSD, and other mental disorders.
AB  - The well-documented association between combat-related PTSD (C-PTSD) and other
      mental disorders may be an artifact of shared familial vulnerability. This study
      uses a co-twin control design to examine whether the association between C-PTSD
      and other mental disorders persists after adjusting for shared familial
      vulnerability. Data were from male monozygotic twin pairs in the Vietnam Era Twin
      Registry. Logistic regression analyses demonstrated that combat exposure,
      adjusted for C-PTSD, was significantly associated with increased risk for alcohol
      and cannabis dependence and that C-PTSD mediated the association between combat
      exposure and both major depression and tobacco dependence. We conclude C-PTSD
      comorbidity persists after controlling for shared vulnerability. Combat exposure
      is directly and indirectly, through C-PTSD, associated with increased risk for
      other mental disorders.

PMID- 14584628
TI  - A pilot study of PTSD symptoms among Kalahari Bushmen.
AB  - This study reflects an attempt to assess posttraumatic stress disorder (PTSD) in
      a radically nonwestern culture, that of the Kalahari Bushmen, the Ju/'hoansi.
      After translating DSM-IV PTSD symptoms into their difficult and click-laden
      language, potential participants were nominated by village elders who were aware
      of domestic violence and symptoms during the preceding year. Ten men and 10
      women, identified as meeting Criteria A, E, and F, were interviewed regarding
      their symptoms. Thirty-five percent of the sample met the criteria for PTSD for
      incidents occurring within the past year. All participants met the reexperiencing
      and arousal criteria but many otherwise distressed participants did not meet the
      avoidance criterion for PTSD. These results compare closely with PTSD assessments
      in other non-Western societies, while providing some empirical support of two new
      ideas about how the avoidance behaviors in such societies might be reconciled
      with information-processing theories of PTSD.

PMID- 14584629
TI  - A preliminary examination of treatment for posttraumatic stress disorder in
      chronic pain patients: a case study.
AB  - Manualized treatments have become popular, despite concern about their use when
      comorbid diagnoses are present. In this report, the efficacy of manualized
      posttraumatic stress disorder (PTSD) treatment was examined in the presence of
      chronic pain. Additionally, the effect of PTSD treatment on chronic pain and
      additional psychiatric diagnoses was explored. Six female patients with both PTSD
      and chronic pain following motor vehicle accidents were treated for PTSD using a
      multiple baseline design. The results indicate that manualized treatment for PTSD
      was effective in reducing PTSD symptoms in these patients. Although there were no
      changes in subjective pain, there were pain-related functional improvements and
      reductions in other psychiatric diagnoses for the majority of patients.

PMID- 14584630
TI  - Are children of Holocaust survivors less well-adapted? A meta-analytic
      investigation of secondary traumatization.
AB  - H. Keilson (1979) coined the term "sequential traumatization" for the
      accumulation of traumatic stresses confronting the Holocaust survivors before,
      during, and after the war. A central question is whether survivors were able to
      raise their children without transmitting the traumas of their past. Through a
      series of meta-analyses on 32 samples involving 4,418 participants, we tested the
      hypothesis of secondary traumatization in Holocaust survivor families. In the set
      of adequately designed nonclinical studies, no evidence for the influence of the
      parents' traumatic Holocaust experiences on their children was found. Secondary
      traumatization emerged only in studies on clinical participants, who were
      stressed for other reasons. A stress-diathesis model is used to interpret the
      absence of secondary traumatization in nonclinical offspring of Holocaust
      survivors.

PMID- 14584631
TI  - Fear-potentiated startle and posttraumatic stress symptoms in urban police
      officers.
AB  - We studied the effects of increasing threat conditions on self-reported emotion,
      eyeblink electromyogram, and skin conductance responses to startling sounds in 55
      police officers who endorsed a range of PTSD (posttraumatic stress disorder)
      symptoms. We found that contextual threat affected both physiologic and self
      reported emotional responses. Greater PTSD symptom severity was related to
      greater physiologic responses under the low and medium but not under the high
      threat condition. The relationship between PTSD symptoms and physiologic
      responses was neither explained by self-reported emotional responses nor
      preexisting reported exaggerated startle symptoms. Our results emphasize the
      importance of contextual threat and suggest that laboratory measures of startle
      improve upon self-reported exaggerated startle alone in indexing PTSD symptom
      severity in urban police officers.

PMID- 14584632
TI  - Positive and negative changes following vicarious exposure to the September 11
      terrorist attacks.
AB  - The negative effects of vicarious traumatic exposure are well known. However,
      less is known about potential positive changes following vicarious exposure.
      Respondents living in Britain (n = 108) were surveyed about their vicarious
      exposure to the terrorist attacks of September 11. They also completed measures
      of their perceptions of the events of September 11, and positive (valuing friends
      and family more) and negative changes (loss of meaning, greater anxiety). Results
      revealed that respondents who perceived the terrorist attacks to be an attack on
      their own values and beliefs, or the work of religious fanatics, were more likely
      to report positive changes. Negative and positive psychological changes were
      positively associated.

PMID- 14584633
TI  - Spirituality, resilience, and anger in survivors of violent trauma: a community
      survey.
AB  - This study evaluates the relationship between spirituality, resilience, anger and
      health status, and posttraumatic symptom severity in trauma survivors. A
      community sample (N = 1,200) completed an online survey that included measures of
      resilience, spirituality (general beliefs and reincarnation), anger, forgiveness,
      and hatred. In survivors of violent trauma (n = 648), these measures were
      evaluated with respect to their relationship to physical and mental health,
      trauma-related distress, and posttraumatic symptom severity. Using multivariate
      regression models, general spiritual beliefs and anger emerged in association
      with each outcome, whereas resilience was associated with health status and
      posttraumatic symptom severity only. Forgiveness, hatred, and beliefs in
      reincarnation were not associated with outcome. The importance of these findings
      to treating trauma survivors is discussed.

PMID- 14584634
TI  - Psychometric properties of the PTSD Checklist-Civilian Version.
AB  - We examined the psychometric properties of the PTSD Checklist (PCL), a self
      report instrument designed to assess symptoms of posttraumatic stress disorder.
      Three hundred ninety-two participants recruited in a university setting completed
      the PCL in addition to several well-established self-report instruments designed
      to assess various forms of psychopathology (e.g., depression, general anxiety,
      PTSD). Ninety participants returned for readministration of selected measures.
      Findings provided support for psychometric properties of the PCL, including
      internal consistency, test-retest reliability, convergent validity, and
      discriminant validity. Additional strengths of the PCL are discussed.

PMID- 14584635
TI  - Symptom exaggeration and compensation seeking among combat veterans with
      posttraumatic stress disorder.
AB  - Combat veterans seeking treatment for posttraumatic stress disorder (PTSD) tend
      to report high levels of psychopathology on self-report instruments. The purpose
      of the current archival study was to replicate research on the relationships
      among symptom exaggeration, attempts to obtain compensation, and treatment
      outcome on the Beck Depression Inventory, the Mississippi Scale for Combat
      Related PTSD, and selected MMPI-2 and MCMI-II subscales. Results indicated that
      symptom exaggeration as defined by an MMPI-2 F-K index over 13 was related to
      higher scores on all scales examined. Compensation seeking was not related to
      assessment scores or exaggeration. Neither compensation seeking nor exaggeration
      was related to treatment outcome. Limitations of the study and implications for
      future research are discussed.

PMID- 14584636
TI  - Imagery rehearsal in the treatment of posttraumatic nightmares in Australian
      veterans with chronic combat-related PTSD: 12-month follow-up data.
AB  - Nightmares are often a distressing symptom for veterans with chronic combat
      related posttraumatic stress disorder (PTSD). A psychological treatment that has
      recently shown considerable promise is Imagery Rehearsal Therapy (IRT). In a
      pilot study by the current authors, IRT was demonstrated to be effective in the
      treatment of posttraumatic nightmares in a group of combat veterans up to 3-month
      posttreatment. This study reports the 12-month follow-up data of the pilot study,
      examining the longer term outcome of the IRT treatment. Twelve Australian Vietnam
      veterans with chronic combat-related PTSD were treated with 6 once weekly
      sessions of imagery rehearsal and assessed using standardised measures of
      nightmare frequency and intensity, PTSD, depression, anxiety and broader
      symptomatology at intake, posttreatment, and 3-and 12-month follow-up.
      Significant improvements in targeted nightmare frequency and intensity were
      evident to 12-month posttreatment. Similarly, improvements in overall PTSD,
      depression, anxiety, and broader based symptomatology were also maintained to 12
      months. This study provides preliminary evidence that the positive treatment
      effects of IRT on posttraumatic nightmares, PTSD, and broader symptomatology in
      males with chronic combat-related PTSD are maintained in the longer term.

PMID- 14584637
TI  - The clinical relevance of a partial remission specifier for posttraumatic stress
      disorder.
AB  - The clinical relevance of a partial remission specifier for posttraumatic stress
      disorder (PTSD) was examined. Using a subgroup of outpatients from the Rhode
      Island Methods to Improve Diagnostic Assessment and Services project who met
      criteria for lifetime PTSD (N = 261), participants with current PTSD, PTSD in
      partial remission, and PTSD in full remission were compared on various indices of
      impairment. A substantial number (n = 75) of patients met criteria for PTSD in
      partial remission (28.7%). Outpatients in partial remission of PTSD displayed
      comparable levels of social and employment functioning as those with current
      PTSD, and over half of these patients requested treatment for their symptoms.
      Results support the clinical utility of a partial remission specifier for PTSD.

PMID- 14584638
TI  - Posttraumatic stress disorder (PTSD) in the Armed Forces: health economic
      considerations.
AB  - This paper addresses the use of health economics in relation to posttraumatic
      stress disorder (PTSD) in the Armed Forces, with a view to assessing the
      feasibility of carrying out future evaluative studies. Although psychological and
      pharmacological interventions can be used to treat PTSD, no economic evaluations
      are known to exist. There is an economic burden associated with PTSD, and
      treatments require the use of scarce resources. Health economics provides tools
      (including cost-effectiveness, cost-benefit, and cost-utility analyses) to
      ascertain the relative efficiency of different treatment options. The paper
      concludes that the quality of life and resource consequences of PTSD require a
      better understanding of the economics of the disorder and the alternative ways to
      treat it.

PMID- 14584639
TI  - Follow-up of young road accident victims.
AB  - The aim of this study was to follow-up a group of children and young people
      previously examined for psychological sequelae following road traffic accidents.
      The group was assessed 18-month postaccident to assess the severity of continuing
      symptoms and examine any emergence of delayed onset of posttraumatic stress
      reactions. Participants (N = 31) completed the Revised Impact of Event Scale and
      the Child Posttraumatic Stress Reaction Index. Parents completed the Child
      Behavior Check-List and participated in a semistructured interview. Symptoms of
      PTSD were noted in a quarter of participants as was delayed onset of symptoms.
      The role of avoidance in symptom reporting and continuing disorder is discussed.

PMID- 14584640
TI  - Of "crashes" and "accidents," a comment on Stewart and Lord.
AB  - A. E. Stewart and J. H. Lord (2002) call for abandoning the term motor vehicle
      accident and substituting motor vehicle crash on definitional and patient care
      grounds. We disagree on definitional grounds and because of the absence of
      empirical data from accident survivors to support their contentions.

PMID- 14584641
TI  - Progestins and risk of breast cancer. Much ado about nothing?
AB  - In vivo and in vitro studies; epidemiological and statistical publications
      concerning a possible carcinogenic effect of progesterone--and progestins--raise
      a question mark. Too many contradictions exist in experimental and clinical
      studies. A very small increased risk of breast cancer with estrogen therapy has
      been shown; however bias are often present. It is not clearly demonstrated that
      the adjunction of progestin to estrogen significantly increases the risk, nor
      that it brings about a protective effect. Some recent works seem to indicate that
      continuous estroprogestin replacement therapy might be deleterious, while a
      sequential regimen would be not. This is to be confirmed. The results of the
      Women's Health Initiative Study have been analyzed. The data and conclusions of
      the medical literature should be interpreted very cautiously.

PMID- 14584642
TI  - The current status of HPV DNA testing.
AB  - Infection with high-risk types of HPV underlies most cases of high-grade cervical
      intraepithelial neoplasia (CIN) and practically all cases of invasive cervical
      cancer. Currently, cervical HPV DNA is detected by means of PCR and sandwich
      capture molecular hybridization methods. Research has focused on the potential
      role of HPV testing in three conditions: screening for cervical neoplasia, triage
      of women with low-grade lesions and follow-up after conservative surgical
      treatment for CIN. Concerning the first condition, HPV testing does not seem to
      offer an obvious advantage over traditional cytology screening, mainly due to
      false positive results in younger women with transient HPV infection. A possible
      exemption to this is the case of middle-aged women and low-resource settings,
      where the excellent sensitivity of a HPV test is desirable. Although data are
      controversial regarding low grade lesions, results from randomized studies
      indicate that HPV testing could be useful in a triage of women with an initial
      cytological diagnosis of ASCUS, where detection of DNA of a high-risk type should
      lead to colposcopy. Although there is a lack of randomized controlled trials in
      this field, data from observational studies indicate that HPV DNA testing after
      conservative surgical treatment for CIN may be very sensitive and detect early
      residual and recurrent disease.

PMID- 14584643
TI  - How to avoid the uncertainties of intraoperative examination of the sentinel
      lymph node in breast cancer?
AB  - Numerous researchers have confirmed the diagnostic relevance of the sentinel
      lymph node (SLN) examination in breast carcinoma. Many technical problems are
      analyzed which are correlated with the intraoperative examination of the SLN and
      its sensitivity and specificity. In order to avoid the incidence of false
      positive or false negative intraoperative diagnoses, the authors propose the
      examination of SLN under local anesthesia, awaiting its definitive analysis
      before carrying out tumorectomy and/or axillary lymphadenectomy.

PMID- 14584644
TI  - Methylation: a second hit in the two-hit hypothesis.
AB  - This case illustrates that methylation of one BRCA1 allele may serve as the
      second hit in a patient with a diploid locus and missense mutation on the other
      allele.

PMID- 14584645
TI  - Cancer of the cervix with endometrial extension treated by radiotherapy: a
      retrospective case-control study.
AB  - BACKGROUND: Studies determining prognosis of cancer of the cervix with
      endometrial extension (CCEE) in a case-control fashion are scant. METHODS: A case
      control retrospective study of 20 women with CCEE and 16 patients with cervical
      cancer not extending to the endometrium (CCNEE) treated by radiation was
      undertaken. The patient groups were matched for age, disease stage, the presence
      of bulky/barrel-shaped tumor in the cervix, intercurrent illness, total radiation
      dose, and hemoglobin level. The overall mean follow-up was 54 months (range 8 to
      218 months). RESULTS: The numerical rates of local and systemic failure as well
      as 5-year survival were worse for patients with CCEE versus CCNEE. However, the
      observed differences were not statistically significant. CONCLUSION: Involvement
      of the endometrium by cancer of the cervix seems to confer a worse outcome among
      cervical cancer patients treated by radiation alone.

PMID- 14584647
TI  - High-risk human papillomavirus type does not predict grade of cervical
      intraepithelial neoplasia.
AB  - PURPOSE OF INVESTIGATION: The aim of this study was to examine whether HPV
      testing specificity for cervical intraepithelial neoplasia (CIN) grades 2 or 3
      could be improved by restricting the range of HPV types classified as 'high
      risk'. METHODS: DNA was extracted from 28 CIN I, nine CIN II and 13 CIN III
      formalin-fixed, paraffin-embedded biopsies. HPV type was determined by General
      Primer mediated 5+/6+ PCR assay. RESULTS: The prevalence of specific HPV types
      among the different grades of CIN and the relationship to the referral smear
      diagnosis was examined. HPV type-16 alone was more highly associated with CIN
      grade (p < 0.0001; Specificity = 0.93; Sensitivity = 0.68) than was the group of
      HPV types collectively classed as high-risk (p = 0.025; Specificity = 0.23;
      Sensitivity = 1.00). CONCLUSIONS: These data suggest HPV testing specificity
      could be improved simply by including a separate test for HPV-16. In conjunction
      with previous studies, the data also suggests redefinition of the high-risk HPV
      category to take into account the differing degrees of oncogenicity of high-risk
      HPV types.

PMID- 14584646
TI  - Development of an evidence-based algorithm for the management of cervical cancer.
AB  - OBJECTIVE: To develop a description of the management of cervical cancer to
      support locally developed, regional guidelines and to identify the level of
      primary research evidence to support it. DESIGN: Development of a flow-charted
      algorithm, using regional guidelines and clinician consensus. A Medline
      literature search for primary research was done to validate the algorithm and
      selection of papers, to verify if they were valid according to pre-defined
      criteria and to compare algorithm management with an alternative. MAIN OUTCOME
      MEASURE: The highest level of evidence for algorithm management was based on the
      design of the supporting research. RESULTS: Twenty percent of the algorithm is
      supported by level I evidence (randomised controlled trials), 70% by level II
      evidence (cohort studies) and 10% by level IV evidence (expert opinion or case
      series). Level II evidence supports the management of Stage Ia, squamous cell
      carcinoma by cone biopsy or a simple hysterectomy. This level of evidence also
      applies to research on the management of Stages Ib-IIa, by radical hysterectomy
      and pelvic lymphadenectomy followed by radiotherapy, if the lymph nodes are
      positive. Radiotherapy to treat Stages IIb-IV cervical cancer is supported by
      level I evidence. The management of Stage I adenocarcinoma is supported by level
      II evidence. CONCLUSIONS: Evaluations of the effect of informing clinicians of
      the strengths of the proposed management are now required, as constructing
      evidence-based algorithms is worthwhile, only if they are likely to affect
      clinical practice.

PMID- 14584648
TI  - Successful treatment with weekly paclitaxel in a patient with recurrent
      endometrial cancer. A case report.
AB  - The best treatment for recurrent endometrial cancer is still uncertain, although
      weekly paclitaxel has shown some promise in the management of this disease. In
      this report we present a patient with recurrent endometrial cancer treated with
      weekly paclitaxel. Serial power Doppler angiography was used to assess the
      effects of therapy. The response was good, suggesting that recurrent endometrial
      cancer may be successfully treated with weekly paclitaxel and effectively
      monitored with power Doppler angiography.

PMID- 14584649
TI  - Laparoscopic gonadectomy in a case of a dicentric fluorescent Y-chromosome
      mosaicism with Turner-like phenotype and virilized external genitalia.
AB  - In few cases of Turner syndrome the karyotype reveals the presence of an
      additional Y-bearing cell line, which is referred to as a borderline case of
      mixed gonadal dysgenesis. We report a 20-year-old woman with primary amenorrhea,
      virilization and a few Turner stigmata, who revealed rare mosaicism of 45,X/46,X
      dic (Y; 5)(q12; q11), +5/46,X, der (Y), which was detected by conventional G
      banding and multicolor spectral karyotyping. She underwent laparoscopic
      gonadectomy in which mixed gonadal dysgenesis was found and both gonads were
      removed. No evidence of gonadoblastoma was noted on the gonads. Virilization
      improved postoperatively. We recommend gonadectomy via laparoscope in women
      presenting with Turner-like phenotype, virilization and the presence of a Y
      chromosome. This report describes the role of cytogenetic and molecular genetic
      investigations in the definition of mosaicism in Turner syndrome.

PMID- 14584650
TI  - Endometrial cancer: factors affecting survival.
AB  - PURPOSE: To evaluate the influence in survival of clinical and pathological
      findings in patients with endometrial cancer. METHODS: In 152 women treated for
      endometrial cancer from 1982 to 1996, personal, obstetrical and oncological data,
      histology, grade, myometrial invasion, peritoneal cytology, FIGO stage and
      treatment were correlated with survival. RESULTS: Mean age was of 60.3 +/- 11.1
      years old. Eight patients had a previous history of other neoplasms (seven of
      them gynecological). The mean clinical complaint was abnormal uterine bleeding.
      The most common histological type was endometrioid (84.9%), only 51 cases did not
      show myometrial invasion and 119 women were in Stage I at diagnosis. Peritoneal
      cytology was negative in 113 patients. Seven patients out of 85 in whom
      lymphadenectomy was performed showed metastasis. Seventeen of the patients died.
      The factors influencing survival were age, myometrial invasion and lymph node
      metastasis. CONCLUSION: Lack of myometrial invasion, absence of lymph node
      metastasis and age younger than 60 years seem to be the most significant
      predicting factors of survival.

PMID- 14584651
TI  - Primary squamous cell carcinoma of the breast.
AB  - Primary squamous cell carcinoma of the breast is a rare neoplasm. We herein
      report two cases of primary squamous cell carcinoma of the breast, each with a
      different clinical manifestation. A 75-year-old patient with bilateral breast
      cancer and a 73-year-old woman with a mastitis carcinomatosa. Histopathology
      revealed that both tumours were squamous cell carcinomas. In the first case there
      was a coexisting adenocarcinoma in the contralateral breast. The diagnostic and
      therapeutic challenges are discussed in a review of the literature. The initial
      management of primary squamous cell carcinoma should be slightly different to
      that of more common types of breast cancer.

PMID- 14584652
TI  - Identification of the sentinel lymph node stained with blue dye in breast cancer
      patients.
AB  - PURPOSE: This study aimed to evaluate the reproducibility of sentinel
      lymphadenectomy in breast cancer patients (T1N0M0 and T2N0M0) and its possibility
      of predicting the total axillary behavior. METHODS: A total of 25 patients were
      evaluated, all presenting palpable mammary nodes between 1.5 and 5 cm (T1 and
      T2), with clinically negative axillary lymph nodes (N0). After an incisional
      biopsy of the tumor and histopathological confirmation of invasive breast
      carcinoma, a study of the sentinel lymph node took place with a peritumoral
      injection of 4 ml of blue dye at 2.5%. After waiting for 15 to 20 minutes, a
      search for the blue stained lymphatic vase in the axillary fat was carried out,
      which would lead to the sentinel lymph node, stained or not. At that point, a
      mastectomy (20 patients) or a quadrantectomy (5 patients) was performed, both
      with axillary lymphadenectomy at grades 1, 2 and 3. The sentinel lymph nodes and
      the material from the axillary dissection were sent separately for an
      anatomicopathological test in paraffin. RESULTS: The lymph nodes were identified
      in 19 patients, which represented a 76% detection rate. There was a concordance
      between the sentinel lymphadenectomy and the standard axillary dissection in
      68.4% of the patients. The false-positive and the false-negative rates observed
      were 10% and 55.5%, respectively. A higher detection rate was found in tumors
      larger than 2 cm and situated in external quadrants. CONCLUSIONS: Sentinel
      lymphadenectomy identified the sentinel lymph node in the majority of the
      patients in this study, although the high rate of false-negatives observed
      prevented an accurate staging.

PMID- 14584653
TI  - Laparoscopically assisted modified radical vaginal hysterectomy (type II) with
      pelvic lymphadenectomy: ultrasonic operative technique.
AB  - OBJECTIVE: The aim of this study was to incorporate an ultrasonic operative
      laparoscopic technique to complete a type II laparoscopically-assisted modified
      radical vaginal hysterectomy (LARVH) and pelvic lymph node dissection (PLND) in
      early cervical cancer. METHODS AND MATERIALS: LARVH type II and PLND using a
      laparoscopic ultrasonic operative technique and conventional vaginal surgery were
      indicated in five cases of early cervical cancer (IA2). RESULTS: Complete pelvic
      lymphadenectomy and the laparoscopic phase of modified radical vaginal
      hysterectomy were successfully performed using ultrasonic instruments in all
      women. Uterine artery and ureteral dissection with resection of the
      cervicovesical fascia, cardinal and uterosacral ligaments were successful with
      ultrasonically activated instruments only. CONCLUSION: Our initial experience
      with laparoscopically assisted radical vaginal hysterectomy type II confirmed
      that the use of a minimally invasive ultrasonic technique is feasible. Further
      investigations into the indications of disease where laparoscopic surgery is
      appropriate in the management of early cervical carcinoma are required.

PMID- 14584654
TI  - Laparoscopic surgery in treatment of stage IIb cervical cancer after neoadjuvant
      chemotherapy. A case report and review of the literature.
AB  - BACKGROUND: A detailed operative procedure of laparoscopic radical hysterectomy
      (type III) with pelvic and aortic lymphadenectomy after neoadjuvant chemoterapy
      in treatment of Stage IIb cervical cancer is described. CASE REPORT: A 50-year
      old patient with Stage IIb squamous cell carcinoma of the uterine cervix, who
      initially was not surgically resectable, received three courses of neoadjuvant
      chemotherapy that included ifosfamide 5 g/m2, cisplatin 50 mg/m2 and paclitaxel
      175 mg/m2 (TIP). Following a partial clinical response to chemotherapy, the
      patient underwent laparoscopic type III radical hysterectomy with bilateral
      salpingo-oophorectomy and pelvic and paraaortic lymphadenectomy. The surgical
      procedure lasted 250 minutes. Blood loss was 310 ml. The patient was discharged
      on postoperative day 4. The mean length of the resected parametria and paracolpia
      was 4.1 cm and 2.0 cm, respectively. The number of dissected lymph nodes was
      48:29 pelvic and 19 paraaortic nodes. No major intraoperative or postoperative
      complications occurred. The patient also underwent adjuvant radiation therapy.
      Follow-up was performed at six months so far. CONCLUSIONS: This experience
      suggests that such a surgical procedure is safe. Laparoscopic radical
      hysterectomy potentially allows for decreased perioperative morbidity and blood
      loss, faster recovery and better cosmetic results. Large studies with long term
      follow-up are needed to confirm that this approach may be proposed as an
      alternative to conventional surgery.

PMID- 14584655
TI  - Pelvic and paraaortic lymph node metastasis in clinical stage I endometrial
      adenocarcinoma: an analysis of 58 consecutive cases.
AB  - OBJECTIVE: The aim of this study was to evaluate the importance of complete
      surgical-pathologic staging in clinical Stage I endometrial adenocarcinomas.
      METHODS: 58 consecutive women with clinical Stage I endometrial adenocarcinomas
      were investigated. RESULTS: Isolated paraaortic lymph node invasion was found in
      one patient without pelvic node invasion (5%). CONCLUSIONS: We recommend a
      complete lymphadenectomy instead of selective lymphadenectomy. With this practice
      the real stages of the cases can be determined and over treatment can be avoided.

PMID- 14584656
TI  - Pelvic inflammatory disease is a risk factor for cervical cancer.
AB  - The acquisition of human papillomavirus (HPV), the most important etiological
      agent of cervical cancer, does not cause clinical complaints. Although HPV
      spreads together with agents causing pelvic inflammatory disease (PID) with
      complaints forcing the patient to seek medical advice, PID has not yet been
      evaluated as a predictor of cervical cancer. The present study aimed to determine
      the relationship between PID and HPV in order to evaluate the possible risk
      factor role of PID for cervical cancer. Two groups of patients were studied: (i)
      2,215 women with PID; (ii) 4,217 women participating in a cervical cancer
      screening programme who were found to have cytological atypia, mucopurulent
      cervicitis or other colposcopically detected disorders but were free of symptoms
      of PID. The presence of HPV and other STD agents in cervical smears was detected
      with polymerase-chain reaction. HPV prevalence was 33.74% in patients with PID
      and 26.40% in the group of women without PID (p < 0.001). This suggests that
      patients suffering from PID apparently have a higher risk of cervical cancer.

PMID- 14584657
TI  - Is pretreatment hemoglobin level a predictor of complete response to salvage
      chemotherapy for recurrent platinum-pretreated ovarian carcinoma?
AB  - PURPOSE OF INVESTIGATION: The aim of this retrospective study was to correlate
      some patient characteristics at relapse, including also baseline hemoglobin
      levels, with complete response rate and survival following second-line
      chemotherapy for recurrent platinum-pretreated ovarian carcinoma. METHODS: The
      investigation was conducted on 63 patients who received salvage chemotherapy with
      different agents for clinically detectable recurrent ovarian carcinoma following
      initial surgery and first-line platinum-based chemotherapy. Some patient
      characteristics at relapse (patient age, serum CA 125 level, baseline hemoglobin
      level, number of recurrence sites, ascites, platinum-free interval, and treatment
      free interval) were related to complete response rate to salvage chemotherapy and
      survival after recurrence. Median baseline hemoglobin level was 11.6 g/dl (range,
      7.5-15.0 g/dl). RESULTS: Second-line chemotherapy obtained a complete response in
      17 (27.0%) patients and a partial response in 11 (17.5%), whereas stable disease
      and progressive disease were detected in 19 (30.1%) and 16 (25.4%) patients,
      respectively. By univariate analysis, complete response rate was related to
      baseline hemoglobin level (p = 0.0019), platinum-free interval (p = 0.0012) and
      treatment-free interval (p = 0.0048). Multiple logistic regression showed that
      platinum-free interval (p = 0.0107) and baseline hemoglobin level (0.0312) were
      independent predictors of complete response. Patients with baseline hemoglobin
      levels >11.6 g/dl had a 5.338 higher chance of obtaining a complete response when
      compared to those with lower hemoglobin values. The platinum-free interval was
      the only independent prognostic variable for survival after recurrence (p =
      0.0141), whereas baseline hemoglobin level was not related to survival at
      univariate nor at multivariate analysis. CONCLUSIONS: Baseline hemoglobin level
      is an independent predictor of complete response to salvage chemotherapy in
      patients with recurrent platinum-pretreated ovarian carcinoma. Attention must be
      paid to anemia correction in these patients, with the aim of improving both the
      chance of response to salvage treatment and the quality of life.

PMID- 14584658
TI  - The relationship between expression of p53/bcl-2 and clinicopathological criteria
      in cervix squamous cell carcinomas.
AB  - OBJECTIVE: Thirty cases with squamous carcinomas of cervix who underwent total
      abdominal hysterectomy and bilateral salphingo-oopherectomy were reviewed
      histopathologically. MATERIALS AND METHODS: The tissues were stained
      immunohistologically with p53 and bcl-2. Ten cases were selected as well
      differentiated (large cell keratinizing) carcinoma, ten cases moderately
      differentiated (large cell non keratinizing) carcinoma and ten cases poorly
      differentiated carcinoma (includes small cell squamous cell carcinoma). RESULTS:
      We observed 11 cases (36.6%) with bcl-2 and 13 cases (43.3%) with p53 positivity.
      P53 expression showed the opposite correlation to bcl-2 staining. CONCLUSION: A
      decrease in bcl-2 reactivity and an increase in p53 positive staining was noted
      as the histological differentiation worsened.

PMID- 14584659
TI  - The importance of fine needle aspiration biopsy and sonographic evaluation of
      parametria in cervical cancer.
AB  - OBJECTIVE: The aim of study was to estimate of the value of fine needle
      aspiration biopsy (FNAB) and transvaginal ultrasonography (TVS) in the
      preoperative assessment of the parametria in cervical cancer. We compared
      parametrial infiltration before and postoperatively by histopathology to verified
      and confirmed staging of disease. Correct staging qualification, especially
      evaluation of the parametrium, is very useful in choosing an adequate method of
      treatment, and thereby in patient survival. MATERIAL AND METHOD: 52 women (median
      age 56 years, range 33-85) with cervical cancer in Stage Ib and 49 (median age
      51, range 36-71) in Stage II and III, were included in the study. Assessment of
      parametrial invasion before treatment was performed by fine needle aspiration
      biopsy (FNAB) with endovaginal ultrasound assistance. The sonographic evaluation
      of parametria was performed by Siemens Sonoline Versa Pro with a transvaginal 7
      MHz mechanical transducer with a biopsy guide and 21-gauge needle. The probe was
      covered with a disposable latex sheath filled with ultrasound gel. The aspirated
      material was placed on a glass slide, fixed in 95% alcohol and submitted to
      cytologic evaluation. All of the patients with cervical cancer in Stage Ib
      underwent a Wertheim-Meigs hysterectomy. The preoperative findings were compared
      with data obtained by histopathology findings. Moreover, in the whole group of
      101 patients a comparison of FNAB and sonography was performed. The sensitivity,
      specificity and diagnostic accuracy of this method were evaluated. RESULTS:
      Parametrial involvement assessed postoperatively by histopathology, in clinical
      Stage Ib cervical cancer was found in eight of 52 cases (15.4%). FNAB of
      parametrial involvement in the operated group was accurate in 14 of 18 (accuracy-
      83%, sensitivity--78%, specificity--84%, PPV--50%, NPV--95%). Sonographic
      assessment of parametrial involvement was correct in 12 of 18 cases (accuracy-
      58%, sensitivity--67%, specificity--56%, PPV--24%, NPV--89%). In the whole group
      of patients (operated and non-operated), sonographic evaluation of parametria
      verified by FNAB was correct in 104 of 202 cases (accuracy--78%, sensitivity-
      71%, specificity--86%, PPV--84%, NPV--74%). CONCLUSIONS: FNAB and TVS assessment
      of the parametria are very useful methods in confirmation of neoplastic
      infiltration. Correct preoperative diagnosis may improve staging, treatment and
      indirectly, survival of patients with cervical cancer.

PMID- 14584660
TI  - Prognostic value of matrix metalloproteinase-9 (gelatinase-B) expression in
      epithelial ovarian tumors.
AB  - PURPOSE OF INVESTIGATION: To determine the expression of matrix metalloproteinase
      9 (MMP-9) expression in malignant and borderline ovarian tumors and its
      correlation to prognosis. METHODS: Forty-five patients with primary epithelial
      ovarian tumors were enrolled in this retrospective study from 1988 to 2002. Only
      malignant (n = 30) and borderline (n = 15) ovarian tumors constituted the study
      group. All cases were surgically staged according to FIGO criteria. Patient
      characteristics and clinico-pathological findings were obtained from hospital
      records. Paraffin-embedded tissue blocks were treated with MMP-9
      immunohistochemical stain. The percentage of the total number of tumors staining
      positively was categorised and awarded a score of 0 to 4: < 5% as 0, < or = 6-25%
      as 1, 26-50% as 2, 51-75% as 3 and 76-100% as 4. The intensity of immunostaining
      was scored on a 3-point scale: 1, weak; 2, moderate and 3, intense. A weighed
      score for each tumor specimen was produced by multiplying the percentage score
      with the intensity score and was defined as the 'epithelial MMP-9 score'. Stromal
      staining was also assessed as weak, moderate and intense. Cases with final
      epithelial MMP-9 scores < or = 6 and > 6 were then recategorised into two groups,
      accordingly. Based on degree of stromal staining, cases were recategorised into
      two final groups as mildly stained and intense or moderately stained. Tumor
      stages were regrouped as early (Stage I-II) and late (Stage III-IV),
      respectively. RESULTS: Mean ages of cases with malignant and borderline ovarian
      tumors were 57.2 +/- 3.1 and 49.7 +/- 2.1 years, respectively. Epithelial MMP-9
      scores were higher in malignant tumors compared to borderline tumors (p = 0.014).
      However, with regard to stromal MMP-9 staining, no significant difference was
      observed among malignant and borderline tumors (p = 0.113). Among malignant
      ovarian tumors, epithelial MMP-9 scores did not differ between early versus late
      staged and well versus poorly differentiated tumors. Median survival time of
      cases with epithelial MMP-9 scores < or = 6 and > 6 were 24 months and 32 months,
      respectively (log-rank: 0.93, p = 0.335). Cases with weak stromal MMP-9 staining
      had a longer median survival (48 months) compared to cases with moderate or
      intense stromal MMP-9 staining (24 months, log-rank: 4.46, p = 0.03). CONCLUSION:
      Epithelial MMP-9 expression generally appears in the malignant form of ovarian
      tumors compared to borderline tumors. MMP-9 expression in the stroma but not in
      the epithelium contributes to poor survival in ovarian cancers.

PMID- 14584661
TI  - Adjuvant chemotherapy following surgery in the management of uterine sarcomas.
AB  - OBJECTIVE: The aim of this study was to investigate the use of imaging tools in
      the diagnosis of uterine sarcomas, and to evaluate the effect of the adjuvant
      chemotherapy for uterine sarcomas. PATIENTS AND METHODS: The data of 29 patients
      with uterine sarcomas who received cytostatic polychemotherapy between 1990 and
      2000 at the Oncological Division of the Ist Department of Obstetrics and
      Gynecology, Semmelweis University were evaluated by the authors. Symptoms leading
      to diagnosis and methods of diagnosis were examined. Vascular changes shown by
      two-dimensional, color and pulsed Doppler ultrasonography were observed. For
      staging the currently accepted FIGO method was adopted. Most of the patients
      underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH &
      BSO). In each case we administered adjuvant combination chemotherapy according to
      the CYVADIC-protocol. The effect of adjuvant chemotherapy was evaluated. RESULTS:
      Six patients had Stage I, ten had Stage II, 11 had Stage III, and two had Stage
      IV disease. The mean age of the patients was 53.6 years with a range of 22 to 77
      years. Histopathologic distribution included nine leiomyosarcomas (LMS), 13 mixed
      mesodermal sarcomas (MMS), and seven endometrial stromal sarcomas (ESS). Although
      most patients experienced neutropenia following cytotoxic chemotherapy, other non
      hematologic adverse effects were easy to control. The average progression-free
      interval was 22.14 months, in which no significant difference was found between
      the histologic types. Different stages showed highly varied responses:
      surprisingly, patients in Stage IV with lung metastases were documented to have
      the longest progression-free survival. The three-year survival rate for all
      stages was demonstrated in 34.4% of cases. Patients with progressive disease had
      an average survival period of 4.4 months. CONCLUSIONS: These findings suggest
      that adjuvant cytostatic therapy for patients with distant metastasis confined to
      a single organ may produce better results than expected.

PMID- 14584662
TI  - Microvessel density as a prognostic factor in preinvasive and invasive cervical
      lesions.
AB  - OBJECTIVE: To assess angiogenesis in preinvasive and invasive cervical lesions
      and its prognostic value in squamous cell carcinoma (SCC). METHODS: Twenty-seven
      cervical intraepithelial lesions (CIN I, II and III), 27 Stage Ib-IIa SCC and 12
      normal cervical epithelium were included in the study. Clinico-pathological
      prognostic factors were re-evaluated from the patients' files and previous tissue
      sections. Microvessel density (MVD), a marker for angiogenesis, was assessed from
      new tissue blocks by an immunohistochemical staining method. Statistical tests
      included Kruskall-Wallis analysis, the Mann-Whitney U-test, Fisher's exact t-test
      to analyse the categorical data and Cox regression and Kaplan-Meier survival
      analyses to define the effect of prognosticators on survival. RESULTS: CIN II and
      III lesions had significantly higher MVD counts than normal epithelium and CIN I
      lesions, both of which had similar MVD count. Compared to preinvasive lesions
      invasive SCC had significantly higher MVD counts. Among SCC cases, only pelvic
      lymph node involvement appeared to be independent risk factor on unvariate
      analysis. However, MVD, as a cut-off value of 21 determined by ROC analysis, was
      found to be an independent prognosticator in early stage SCC cases by
      multivariate analysis. CONCLUSION: Despite the small number of enrolled cases,
      the results of this study suggest that angiogenesis involved in the development
      and progression of cervical neoplasms and MVD might be used as a prognostic
      factor.

PMID- 14584663
TI  - Ovarian fibroma: our experience of 34 cases.
AB  - Thirty-four cases of ovarian fibroma are reported. The early symptoms were pelvic
      pain and abnormal uterine bleeding. All patients were in advanced menopause, mean
      age 63, except for one that was normally menstruatuating and was 23 years old. In
      all cases an ultrasound scan TV/TA and CA 125 tests were performed, and
      afterwards all patients were treated with either conservative or radical surgery.
      In addition to the above examinations, color Doppler tests on pelvic vessels were
      performed in 18 cases.

PMID- 14584664
TI  - Failure of sentinel node identification following neo-adjuvant chemo-radiotherapy
      for locally advanced squamous cell carcinoma of the vulva.
AB  - A case of a 70-year-old patient with advanced local vulvar cancer is presented.
      Treatment with neo-adjuvant chemo-radiotherapy for two courses was administered
      and two weeks after completion of treatment the patient underwent wide local
      excision with bilateral inguino-femoral lymph node dissection through three
      separate incisions. Two methods for the evaluation of sentinel nodes-
      lymphoscintigraphy and intraoperative gamma hand-held probe and blue dye
      injection, did not detect any sentinel node on either side. Groin-node dissection
      revealed 23 negative nodes. It is our hypothesis that the non-visualization of
      sentinel nodes in this patient was due to post-irradiation damage to the lymph
      channels.

PMID- 14584665
TI  - A case of adenocarcinoma of the endometrial type mixed with a clear cell
      component that metastasized to the vagina.
AB  - We present a patient with adenocarcinoma of the endometrial type mixed with a
      clear cell component (AMC) that metastasized to the vagina and one of the pelvic
      lymph nodes. She underwent a radical hysterectomy and pelvic and paraaortic
      lymphadenectomy, and then received postoperative adjuvant chemotherapy.
      Histologic features of the endometrial tumor included clear cell adenocarcinoma
      with an approximate 10% extent to endometrioid adenocarcinoma. On the other hand,
      histologic examination on the vaginal tumor predominatly showed clear cell
      adenocarcinoma and also revealed endometrioid adenocarcinoma to a very small
      extent, suggesting metastasis to the vagina from AMC. On immunohistochemical
      examination, expression of vascular endothelial growth factor (VEGF)-A, VEGF-C
      and VEGF-D was apparently stronger in the component of clear cell adenocarcinoma
      than in that of endometrioid adenocarcinoma. She has been a disease-free survivor
      for 26 months. Interestingly, locations of endometrial and vaginal lesions were
      consistent with the sites of an intrauterine device and ring pessary insertion,
      respectively.

PMID- 14584667
TI  - Sclerosing stromal tumor of the ovary: a case report.
AB  - Sclerozing stromal tumor of the ovary is an extremely rare neoplasm occurring
      predominantly in the second and third decades of life. Most patients have
      menstrual irregularities and pelvic pain. Infertility and endometrial pathology
      have also been described. A 34-year-old woman presented with hirsutism and
      oligomenorrhea of three months duration. Ultrasound examination showed a
      heterogeneous right ovarian tumor consisting of predominantly solid tissue with
      several loculated cysts. On T2-weighted pelvic MR images, signal intensities of
      the cystic components were high and those of the solid components were
      heterogeneous, ranging from intermediate-high to high. Dynamic MRI marked early
      enhancement of solid components in the right ovary. The specimen obtained from
      endometrial curettage showed proliferative endometrium. Preoperative serum levels
      of tumor markers were in normal range: preoperative serum levels of testosterone
      (T) (2.42 ng/ml; normal for adult females 0.1-0.8 ng/ml) and
      dehydroepiandrosterone-sulphate (DHEA-S) (232.4 microg/dL; normal for adult
      female, 35-430 microg/dL) were measured and the T value was found increased. At
      laparotomy, a left ovarian mass was found attached to the right infundibulopelvic
      ligament and a left oophorectomy was performed. The mass was described as benign
      by frozen analysis. Definitive histopathological diagnosis was sclerozing stromal
      tumor of the ovary (SST). The histologic features included a pseudolobular
      pattern with focal areas of sclerosis and a two-cell population of spindled and
      polygonal cells. Immunohistochemical studies showed positive smooth muscle actin
      and negative cytokeratin, keratin, S100 and desmin. The T value decreased
      postoperatively (0.57 ng/ml).

PMID- 14584666
TI  - Clear cell ovarian carcinoma in a pregnant woman with a history of infertility,
      endometriosis and unsuccessful IVF treatment.
AB  - Ovarian cancer in pregnancy is a very rare event. We present here the case of a
      37-year-old woman in whom a clear cell ovarian carcinoma was diagnosed in the
      first trimester of pregnancy. This patient had a history of infertility,
      endometriosis and two previous unsuccessful attempts of in vitro fertilization.
      Transvaginal sonography at six gestational weeks revealed a 6 x 4 cm ovarian cyst
      with an internal papillary excrescence. The cyst persisted throughout the first
      trimester, whereas the initial CA 125 value of 226 U/ml dropped to 61 U/ml at 12
      gestational weeks. Exploratory laparotomy and cystectomy was performed at 14
      weeks and the disease was classified as Stage Ic, arising in endometriosis. The
      couple decided to continue with pregnancy and the woman was followed by serial
      sonographic, MRI and CA 125 examinations. A cesarean section, hysterectomy,
      bilateral salpingo-oophorectomy and omentectomy was performed at 34 weeks.
      Histology and cytology were negative for recurrence. Four months later the woman
      and baby are doing well. We review cases of ovarian clear cell carcinoma
      diagnosed during pregnancy and discuss the association of endometriosis,
      infertility, infertility drugs and ovarian cancer.

PMID- 14584668
TI  - A ruptured ovarian endometrioma mimicking ovarian malignancy: case report.
AB  - A 24-year-old single woman was referred to our department due to intermittent
      abdominal pain. Because her serum CA 125 concentration was extremely elevated an
      ovarian malignancy was suspected. At the laparoscopic examination, it was
      determined to be a ruptured endometrioma and serum CA 125 concentrations rapidly
      decreased after surgery.

PMID- 14584669
TI  - Clitoromegaly in type 2 neurofibromatosis: a case report and review of the
      literature.
AB  - OBJECTIVE: Genitourinary neurofibromatosis (NF) is a rare disorder and clitoral
      involvement has been reported infrequently. In the English literature there are
      only 26 reported cases with clitoral involvement in NF. CASE: A 28-year-old
      female with clitoral enlargement, previously diagnosed with NF 2, was
      successfully treated by removal of the clitoral mass that increased in size
      during the previous two years. Clitoroplasty was performed while preserving the
      glans of clitoris. Histopathologic examination revealed plexiform neurofibroma.
      CONCLUSION: To the best of our knowledge the patient is the 27th reported
      clitoromegaly case with NF, but the first case reported with NF 2 or central NF
      in the English literature.

PMID- 14584670
TI  - Arbuscular mycorrhiza: biological, chemical, and molecular aspects.
AB  - Mycorrhizas are the most important mutualistic symbioses on earth. The most
      prevalent type are the arbuscular mycorrhizas (AMs) that develop between roots of
      most terrestrial plants and fungal species of the Zygomycota. The AM fungi are
      able to grow into the root cortex forming intercellular hyphae from which highly
      branched structures, arbuscules, originate within cortex cells. The arbuscules
      are responsible for nutrient exchange between the host and the symbiont,
      transporting carbohydrates from the plant to the fungus and mineral nutrients,
      especially phosphate, and water from the fungus to the plant. Plants adapt their
      phosphate uptake to the interaction with the AM fungus by synthesis of specific
      phosphate transporters. Colonization of root cells induces dramatic changes in
      the cytoplasmic organization: vacuole fragmentation, transformation of the plasma
      membrane to a periarbuscular membrane covering the arbuscule, increase of the
      cytoplasm volume and numbers of cell organelles, as well as movement of the
      nucleus into a central position. The plastids form a dense network covering the
      symbiotic interface. In some of these changes, microtubules are most likely
      involved. With regard to the molecular crosstalk between the two organisms, a
      number of phytohormones (cytokinins, abscisic acid, jasmonate) as well as various
      secondary metabolites have been examined: (i) Jasmonates occur at elevated level,
      which is accompanied by cell-specific expression of genes involved in jasmonate
      biosynthesis that might be linked to strong carbohydrate sink function of AM
      roots and induced defense reactions: (ii) apocarotenoids (derivatives of
      mycorradicin and glycosylated cyclohexenones) accumulate in most mycorrhizal
      roots examined so far. Their biosynthesis via the nonmevalonate methylerythritol
      phosphate (MEP) pathway has been studied resulting in new insights into AM
      specific gene expression and biosynthesis of secondary isoprenoids.

PMID- 14584671
TI  - Drought stress alters the concentration of wood terpenoids in Scots pine and
      Norway spruce seedlings.
AB  - Drought is known to have an impact on the resistance of conifers to various
      pests, for example, by affecting resin flow in trees. Little is known, however,
      about the quantitative and qualitative changes in resin when trees are growing in
      low moisture conditions. We exposed Scots pine (Pinus sylvestris L.) and Norway
      spruce (Picea abies (L.) Karst.) seedlings to medium and severe drought stress
      for two growing seasons and analyzed the monoterpenes and resin acids in the main
      stem wood after two years of treatment. In addition to secondary chemistry, we
      measured the level of nutrients in the needles and the growth response of
      seedlings. After the first year of treatment, drought stress did not affect the
      growth of seedlings, but in the second year, shoot growth was retarded,
      especially in Scots pine. In both conifer species, severe drought increased the
      concentrations of several individual monoterpenes and resin acids. Total
      monoterpenes and resin acids were 39 and 32% higher in severe drought-treated
      Scots pine seedlings than in the controls, and 35 and 45% higher in Norway spruce
      seedlings. In Scots pine needles, the concentrations of nitrogen and phosphorus
      increased, while magnesium and calcium decreased compared to controls. In Norway
      spruce needles, nutrient concentrations were not affected. The results suggest
      that drought stress substantially affects both the growth of conifers and the
      chemical quality of the wood. We discuss the potential trade-off in growth and
      defense of small conifer seedlings.

PMID- 14584672
TI  - Effects of drought stressed cotton, Gossypium hirsutum L., on beet armyworm,
      Spodoptera exigua (Hubner), oviposition, and larval feeding preferences and
      growth.
AB  - The beet armyworm, Spodoptera exigua (Hubner), has been anecdotally reported to
      oviposit more on drought stressed than on nonstressed cotton plants. Using potted
      cotton plants in cages, this study demonstrated that beet armyworms deposited
      3.3, 4.6, and 2.3 times more (P < or = 0.05) eggs on cotton plants that were
      grown on 1500, 1000, and 750 ml water/wk, respectively, than on cotton plants
      grown in well watered (4000 ml water/wk) soil. Third instars, however, showed no
      preference for stressed cotton foliage over nonstressed foliage. Third instar
      beet armyworms raised on well watered cotton plants were 1.5, 2.3, and 2.6 times
      heavier than those reared on cotton grown in the 1500, 1000, and 750 ml water/wk
      plants (P < or = 0.05), respectively. Physiochemical analyses showed that drought
      stressed leaves had significantly greater accumulations of free amino acids that
      are essential for insect growth and development. Soluble protein and soluble
      carbohydrates were also more abundant in stressed leaves compared to nonstressed
      leaves. Despite the apparent increase in nutritional quality in drought stressed
      plants, larval survival was reduced, probably because the limiting factor became
      water. Greater amounts of cotton leaf area were consumed from drought stressed
      leaves (P < or = 0.05) than from nonstressed leaves, probably because the larvae
      had to metabolize greater portions of assimilated energy to supplement body water
      with metabolic water derived from respiration. The association of greater host
      plant nutritional quality to oviposition preference, and conversely, to reduced
      survivorship, is discussed.

PMID- 14584673
TI  - Distribution of norditerpene alkaloids in tall larkspur plant parts through the
      growing season.
AB  - Previous research showed that toxic and total alkaloid pools in tall larkspur
      (Delphinium barbeyi) increased during early growth, then declined precipitously
      during the late flower and pod stage of growth. The objective of this study was
      to measure the concentration and pools of toxic and total alkaloids in tall
      larkspur plant parts, including roots, and to evaluate the changes in these pools
      over the growing season as an estimate of diterpenoid alkaloid kinetics in tall
      larkspur. Twenty entire plants were harvested at each phenological stage:
      beginning of growth in the spring, early flower, early pod, late pod, and
      senescence. The plants were separated into their respective parts, freeze-dried,
      extracted, and analyzed for toxic and total alkaloid concentration, and alkaloid
      pools were calculated. Concentration of toxic and total alkaloids in leaves and
      stems declined as the plants matured, while concentration in flowers and pods
      increased (P < 0.004). Concentration of alkaloids in the root declined in the
      early growth, then increased at the end of the season (P = 0.002). Alkaloid pools
      in the root decreased during early growth, with a corresponding increase of pools
      in foliar parts. In the late flower and pod stage, alkaloid pools in the leaves
      and stems declined rapidly, while the pool in the crown and roots tended to
      increase.

PMID- 14584674
TI  - Chemical stimulants of leaf-trenching by cabbage loopers: natural products,
      neurotransmitters, insecticides, and drugs.
AB  - Larvae of the cabbage looper, Trichoplusia ni (Lepidoptera: Noctuidae), often
      transect leaves with a narrow trench before eating the distal section. The trench
      reduces larval exposure to exudates, such as latex, during feeding. Plant species
      that do not emit exudate, such as Plantago lanceolata, are not trenched. However,
      if exudate is applied to a looper's mouth during feeding on P. lanceolata, the
      larva will often stop and cut a trench. Dissolved chemicals can be similarly
      applied and tested for effectiveness at triggering trenching. With this assay, I
      have documented that lactucin from lettuce latex (Lactuca sativa), myristicin
      from parsley oil (Petroselinum crispum), and lobeline from cardinal flower
      (Lobelia cardinalis) elicit trenching. These compounds are the first trenching
      stimulants reported. Several other constituents of lettuce and parsley, including
      some phenylpropanoids, monoterpenes, and furanocoumarins had little or no
      activity. Cucurbitacin E glycoside found in cucurbits, another plant family
      trenched by cabbage loopers, also was inactive. Lactucin, myristicin, and
      lobeline all affect the nervous system of mammals, with lobeline acting
      specifically as an antagonist of nicotinic acetylcholine receptors. To determine
      if cabbage loopers respond selectively to compounds active at acetylcholine
      synapses, I tested several neurotransmitters, insecticides, and drugs with known
      neurological activity, many of which triggered trenching. Active compounds
      included dopamine, serotonin, the insecticide imidacloprid, and various drugs
      such as ipratropium, apomorphine, buspirone, and metoclopramide. These results
      document that noxious plant chemicals trigger trenching, that loopers respond to
      different trenching stimulants in different plants, that diverse neuroactive
      chemicals elicit the behavior, and that feeding deterrents are not all trenching
      stimulants. The trenching assay offers a novel approach for identifying defensive
      plant compounds with potential uses in agriculture or medicine. Cabbage loopers
      in the lab and field routinely trench and feed on plants in the Asteraceae and
      Apiaceae. However, first and third instar larvae enclosed on Lobelia cardinalis
      (Campanulaceae) failed to develop, even though the third instar larvae attempted
      to trench. Trenching ability does not guarantee effective feeding on plants with
      canal-borne exudates. Cabbage loopers must not only recognize and respond to
      trenching stimulants, they must also tolerate exudates during the trenching
      procedure to disable canalicular defenses.

PMID- 14584675
TI  - Identification and quantitation of allelochemicals from the lichen Lethariella
      canariensis: phytotoxicity and antioxidative activity.
AB  - Phytotoxicity-based extraction and fractionation were employed to separate
      allelochemicals contained in an extract of Lethariella canariensis. Twelve
      phenolic substances were isolated from the phytotoxic fraction "Letharal" of the
      thalli. These were identified by spectroscopic methods, physicochemical
      constants, and HPLC chemical correlation, and determined to be atranol (2),
      chloroatranol (3), hematommic acid (4), chlorohematommic acid (5), methyl
      hematommate (6), methyl chlorohematommate (7) (new compound), ethyl hematommate
      (8), ethyl chlorohematommate (9), methyl beta-orsellinate (10), atranorin (11),
      chloroatranorin (12), and (+)-usnic acid (13). Further identification and
      quantification of these allelochemicals in the environment were conducted by
      HPLC. Several phenolic compounds showed moderate antimicrobial activity. The
      cytostatic activity of the polyphenols was investigated on U937 and HL-60 cells.
      All compounds were assayed, with the exception of 10. The "Letharal" mixture
      decreased cell viability in both cell lines. Protection against lipid
      peroxidation was investigated using brain homogenates. Compounds 2, 3, 6, 8, 11,
      and Letharal decreased H2O2/Fe+2 induced lipid peroxidation in a concentration
      dependent manner, while 10 and 13 were unable to protect tissue against oxidative
      stress.

PMID- 14584676
TI  - Evaluation of root exudates of seven sorghum accessions.
AB  - Seven sorghum accessions were evaluated quantitatively and qualitatively for the
      composition of their root exudates. Utilizing a unique capillary mat growing
      system, root exudates were collected from all sorghum accessions. Exudates were
      subjected to TLC and HPLC analysis to evaluate their chemical composition. Within
      each sorghum accession, variation existed in the amount of exudate produced and
      the chemical constituents of each exudate. Sorgoleone was the predominant
      constituent identified in each accession's exudate. Other closely related
      compounds, including 5-ethoxysorgoleone, 2,5-dimethoxysorgoleone, three other
      minor components (MW = 364, 388, and 402), and one unidentified component
      comprised the minor constituents of the root exudate. Our past work has shown
      that several of these compounds have potent phytotoxic activity as photosystem II
      inhibitors, thereby lending further support to the concept that Sorghum spp. are
      allelopathic and weed suppressive.

PMID- 14584677
TI  - Chemical and olfactory characterization of odorous compounds and their precursors
      in the parotoid gland secretion of the green tree frog, Litoria caerulea.
AB  - When stressed or challenged by a predator, the Australian green tree frog,
      Litoria caerulea, emits a characteristic nutty odor from its parotoid glands.
      This study identifies the source of the odor as the cyclic amide 2-pyrrolidone (2
      PyrO). In addition, we demonstrate the presence of 2-PyrO's straight chain form,
      gamma-aminobutyric acid or GABA, in the frog's glandular secretion and propose an
      odorant-precursor relationship. What role both compounds play in the frog's
      defensive strategy remains unknown. Prolonged exposure to the odor is shown to
      result in adverse effects that may be attributed to a GABAergic mechanism. It is
      our hypothesis, however, that the odor acts as an aposematic signal, indicating
      the toxicity of the frog's nonvolatile secretion.

PMID- 14584678
TI  - Semiochemicals from the predatory stink bug Eocanthecona furcellata (Wolff):
      components of metathoracic gland, dorsal abdominal gland, and sternal gland
      secretions.
AB  - Volatile compounds from the metathoracic glands (MTG), dorsal abdominal glands
      (DAG), and sternal setae of the generalist predatory stink bug Eocanthecona
      furcellata (Wolff) were studied by gas chromatography-mass spectrometry. MTGs of
      both male and female bugs contained (E)-2-decenal as the major component, with
      lesser amounts of (E, E)-2,4-decadienal, (E, Z)-2,4-decadienal, and (E)-2,9
      decadienal. The relative amount of (E)-2,9-decadienal in the MTGs of female bugs
      was higher than in male bugs. There was no dimorphism in the morphology of the
      DAGs of adults. However, the DAG contents of adult bugs were different between
      the sexes. Geraniol was found only in the DAGs of males, and limonene and alpha
      terpineol were found only in the DAGs of females, whereas linalool oxide isomers,
      linalool, neral, and geranial were found in DAGs of both sexes. The DAG contents
      of nymphs were also analyzed, with 4-oxo-(E)-2-hexenal, 4-oxo-(E)-2-octenal,
      tridecane, and tetradecanal being major components. Male bugs but not females
      possess sternal setae, and 6,10,13-trimethyltetradecyl isovalerate was detected
      from extracts of the sternal setae of males. The possible biological significance
      of dimorphism in the contents of the glands in adults is discussed.

PMID- 14584679
TI  - Disruption by conophthorin of the kairomonal response of sawyer beetles to bark
      beetle pheromones.
AB  - Antennally active nonhost angiosperm bark volatiles were tested for their ability
      to reduce the response of three common species of coniferophagous wood-boring
      Cerambycidae to attractant-baited multiple funnel traps in the southern interior
      of British Columbia. Of the nonhost volatiles tested, only conophthorin was
      behaviorally active, disrupting the attraction of sawyer beetles, Monochamus
      spp., to traps baited with the host volatiles alpha-pinene and ethanol and the
      bark beetle pheromones ipsenol and ipsdienol. Conophthorin did not affect the
      attraction of sawyer beetles to the host kairomones alpha-pinene and ethanol in
      the absence of bark beetle pheromones, nor did it have any behavioral effect on
      adults of Xylotrechus longitarsis, which were not attracted to bark beetle
      pheromones. These results indicate that conophthorin does not act as a general
      repellent for coniferophagous Cerambycidae, as it seems to do for many species of
      Scolytidae, but has the specific activity of disrupting the kairomonal response
      of sawyer beetles to bark beetle pheromones.

PMID- 14584680
TI  - Factors accounting for the variability in the behavioral response of the onion
      fly (Delia antiqua) to n-dipropyl disulfide.
AB  - The onion fly Delia antiqua is a specialist herbivore attacking only onions and
      closely related Allium species. n-Dipropyl disulfide (Pr2S2) has long been known
      to be attractive to onion flies in the laboratory and in the field. However, the
      insect's response is highly variable. Using behavioral bioassays we found that
      Pr2S2 was highly attractive to gravid, mated female onion flies,but did not
      stimulate oviposition. The response of female onion flies was concentration
      dependent. The physiological state of the flies (i.e., age, mating status, egg
      load/oviposition experience) also affected their responsiveness. The response of
      both sexes of onion flies varied with age, but females were always more strongly
      attracted than males. Responsiveness of females increased during the first 10
      days after emergence. It stayed at a high level until 21 days after which the
      experiment was terminated. The responsiveness of males reached a maximum at 6-7
      days after which it declined. Mated, gravid females responded more strongly to
      Pr2S2 than unmated, gravid females. Females deprived of the opportunity to
      oviposit were more attracted compared to females that had oviposited on cut
      onions prior to the experiment. Electroantennograms (EAG) of females revealed a
      higher response to stimulation compared to males. The EAG-response of females was
      not affected by mating status.

PMID- 14584681
TI  - Electrophysiological responses of female and male Hypsipyla grandella (Zeller) to
      Swietenia macrophylla essential oils.
AB  - The mahogany shoot borer, Hypsipyla grandella, is one of the most economically
      important Neotropical forest pest insects because it attacks valuable timber of
      the Meliaceae. Despite detailed information on the life cycle of H. grandella,
      factors influencing attack by the shoot borer are not well known.
      Electroantennogram studies of borer antennae indicate that both female and male
      moths elicited significant antennal responses to essential oil of the terminal
      shoots, mature and senescent leaves, in three concentrations. Gamma-himachalene,
      germacrene D, germacrene A, cadina-1,4-diene, hexadecanoic acid, and ethyl
      hexadecanoate appeared in all essential oils from Swietenia macrophylla.
      Germacrene-D and gamma-himachalene were also present in the active essential oil
      of Cedrela odorata and Toona ciliata. These findings suggest that these compounds
      play a role in attracting H. grandella to oviposit on the leaves of these plants.
      The GC-EAD of essential oil from S. macrophylla mature leaves to female H.
      grandella antennae led to the identification of beta-caryophyllene as the main
      constituent responsible for the antennae response.

PMID- 14584682
TI  - Sex pheromone of the cranberry blossom worm, Epiglaea apiata.
AB  - The cranberry blossom worm, Epiglaea apiata (Grote) (Lepidoptera: Noctuidae), is
      a major pest of cranberries in New Jersey. The female sex pheromone of this moth
      was identified as a blend of (Z)-9-hexadecenyl acetate (Z9-16:Ac), (Z)-9
      tetradecenyl acetate (Z9-14:Ac), and tetradecyl acetate (14:Ac) by gas
      chromatographic-electroantennographic detection and gas chromatography-mass
      spectrometry. The ratio of the components in extracts of the female pheromone
      gland was determined to be 65:2:33 of the Z9-16:Ac, Z9-14:Ac, and 14:Ac,
      respectively. The double bond positions of the pheromone components were
      confirmed by dimethyl disulfide derivatization. In addition to the above three
      components, a mixture of C4-C10 aliphatic acids was present in both gland
      extracts and effluvia collections, and the acids elicited significant EAD
      responses from male moth antennae. However, addition of the C4-C10 aliphatic
      acids to the pheromone blend did not significantly increase trap captures. Three
      hundred- and 1000-microg doses of a synthetic blend containing Z9-16:Ac, Z9
      14:Ac, and 14:Ac (65:2:33), on a rubber septum were more attractive to males than
      lower doses.

PMID- 14584683
TI  - Aggregation pheromone of the cereal leaf beetle: field evaluation and emission
      from males in the laboratory.
AB  - The previously identified, male-specific compound of the cereal leaf beetle (CLB,
      Chrysomelidae; Oulema melanopus), (E)-8-hydroxy-6-methyl-6-octen-3-one, was
      studied further with respect to field activity and emission rate from male
      beetles. In a 5-week field experiment in Oregon, the compound was shown to
      function as an aggregation pheromone in attracting male and female CLBs migrating
      from overwintering sites in spring. Traps baited with the synthetic compound (500
      microg per rubber septum) caught 3.3 times more CLBs than control traps. Lower
      doses of the pheromone (50 and 150 microg) were less attractive than the 500
      microg dose. One relatively abundant, volatile compound from the host plant
      (oats), (Z)-3-hexenyl acetate, that elicited responses from beetle antennae was
      not attractive, either by itself or as a synergist of the pheromone. Both sexes
      were captured about equally for all treatments. We also measured daily pheromone
      emission by male beetles in the laboratory. Individual males feeding on oat
      seedlings under greenhouse conditions emitted as much as 6 microg per day, which
      is about 500 times higher than had been previously observed under incubator
      conditions. The pheromone emission rate was at least five times higher during the
      day than at night, and in one male, emission spanned a period of 28 d. The
      release rate of synthetic pheromone from the 500 microg septa was very similar to
      the maximum from single males; thus, future experiments should evaluate even
      higher doses. The field results indicate that the pheromone has potential as a
      monitoring tool for early detection of CLBs as they move from their overwintering
      sites into newly planted cereal crops in spring.

PMID- 14584684
TI  - Overexpression of glutamate decarboxylase in transgenic tobacco plants deters
      feeding by phytophagous insect larvae.
AB  - Gamma-aminobutyrate (GABA) is a ubiquitous four-carbon, non-protein amino acid
      synthesized by glutamate decarboxylase. Previous research suggests that the
      endogenous synthesis of GABA, a naturally occurring inhibitory neurotransmitter
      at neuromuscular junctions, serves as a plant resistance mechanism against
      invertebrate pests. In this study, two homozygous transgenic tobacco lines
      constitutively overexpressing a single copy of a full-length chimeric glutamate
      decarboxylase cDNA and possessing enhanced capacity for GABA accumulation (GAD
      plants), a homozygous transgenic line lacking the gene insert, and wild-type
      tobacco were employed. Tobacco budworm larvae were presented with plant attached
      wild type and transgenic leaves for 4 hr in a feeding preference study. Larvae
      consumed six to twelve times more leaf tissue from wild-type plants than from GAD
      plants. These results suggest that leaf GABA accumulation, which is known to
      occur in response to insect larval walking and feeding, represents a rapidly
      deployed local resistance mechanism.

PMID- 14584685
TI  - Comparison of oligosaccharide compositions in male nuptial secretions of three
      cockroach species of the genus Blattella.
AB  - Male cockroaches of the genus Blattella secrete courtship pheromones from
      abdominal tergal glands. Conspecific females mount courting males and feed on
      their tergal exudates. In the German cockroach, B. germanica, a complex mixture
      of oligosaccharides was previously identified as the major phagostimulants in the
      male tergal secretion. We compared the oligosaccharide compositions of three
      Blattella species from different habitats, B. germanica (house), B. lituricollis
      (field), and B. nipponica (forest), by gas chromatographic (GC) analysis of their
      trifluoroacetylated derivatives. The three possessed a series of
      maltooligosaccharides and oligoglucosyl trehaloses with alpha1-->4 and alpha1-->1
      linkages in common. However, B. germanica was conspicuous for its accumulation of
      a oligoglucosyl trehalose with a alpha1-->6 linkage [O-alpha-D-glucopyranosyl-(1-
      >6)-alpha-D-glucopyranosyl alpha-D-glucopyranoside] as the most prominent
      component of the secretion. Such diversification of the male pheromonal
      compositions within the genus might be reflected by biosynthetic systems in males
      and chemosensory properties in females suited for their natural habitat.

PMID- 14584686
TI  - Guidelines for capillary extraction-capillary gas chromatography: preparation of
      extractors and analysis of aromatic compounds in water.
AB  - The benzene, toluene, ethylbenzene and xylenes system (BTEX) in clean water is
      studied to verify the performance of capillary extraction as an extraction
      preconcentration technique well hyphenated with GC. The approach uses pieces of
      coated capillaries usually 5-30 cm long, trimmed from customary high-resolution
      GC columns but carrying glass press-fits at their ends. The preparation of these
      'capillary extractors' is explained, and their performance is discussed providing
      guidelines for use. Injection by capillary extraction is such that (i) band
      broadening in time is null, and (ii) band broadening in space cannot be higher
      than the extractor length. Speed, cleanliness and operative simplicity of the
      capillary extraction approach are remarkable, pros and cons are complementary to
      those of solid phase microextraction (SPME) or stir bar sorptive extraction
      (SBSE). Capillary extraction-capillary GC analysis of aqueous BTEX samples, in a
      clean water matrix, allows low part-per-billion detection limits, and does not
      require heated injectors or cryofocusing devices.

PMID- 14584687
TI  - Fast fractionation of complex organic extracts by normal-phase chromatography on
      a solid-phase extraction polymeric sorbent. Optimization of a method to
      fractionate wine flavor extracts.
AB  - Some properties of LiChrolut-EN resins as normal-phase sorbent have been studied.
      Retention factors using pentane as solvent range from less than 2 (ethyl esters)
      to more than 56 (fatty acids and vanillin). All retention factors were smaller
      than 2 with dichloromethane. The efficiency of the bed was between 4 and 13
      plates per cm. A method for the fast fractionation of wine flavor extracts has
      been further developed. Wine (75 ml) is extracted on a 0.5 g LiChrolut-EN bed.
      Volatile compounds are recovered in 5 ml of dichloromethane and the extract is
      further concentrated to 0.1 ml. Recoveries of the extraction procedure are above
      85% for all compounds less polar than isoamyl alcohol. This extract is
      fractionated on a bed (5.0 cm height, 0.6 cm internal diameter) packed with 0.55
      g of LiChrolut-EN resins. A first fraction is collected by the elution with 4 ml
      of pentane. A second one with 6 ml of a mixture pentane/dichloromethane (9:1) and
      a final fraction with 4 ml of dichloromethane. The first fraction is enriched in
      ethyl esters and some other non-polar compounds. The second fraction concentrates
      the alcohols and some volatile phenols, while the third is enriched in fatty
      acids, vanillin derivatives and some lactones. The recovery in the fractionation
      is complete. The profile obtained in the fractionation is very stable, and
      becomes distorted only when the column is loaded with an extract containing 80 mg
      of major volatiles (coming from more than 150 ml of wine). The fractionation of
      extracts from different wines showed that the performance of the process does not
      depend on the composition of the extract. Twenty-seven out of 32 studied
      compounds eluted reproducibly mainly in one fraction. The results suggest that
      the method can be applied as an aid for qualitative or quantitative analysis to
      any kind of organic extract as an alternative to liquid chromatography on silica
      gel.

PMID- 14584688
TI  - On-line concentration by field-enhanced sample injection with reverse migrating
      micelles in micellar electrokinetic capillary chromatography for the analysis of
      flavonoids in Epimedium brevicornum Maxim.
AB  - A simple and sensitive micellar electrokinetic capillary chromatography (MEKC)
      method was developed for the separation and determination of six flavonoids in
      Epimedium brevicornum Maxim. Field-enhanced sample injection with reverse
      migrating micelles (FESI-RMM) was used for on-line concentration of the
      flavonoids. An electrolyte containing 20 mM H3PO4, 100 mM SDS, 20% acetonitrile
      and 2% 2-propanol (pH 2.0) was chosen as the electrophoretic buffer. By
      optimizing the stacking conditions, about 40-360-fold improvement in the
      detection sensitivity was obtained for the flavonoids.

PMID- 14584689
TI  - Solid-phase microextraction as a clean-up and preconcentration procedure for
      organochlorine pesticides determination in fish tissue by gas chromatography with
      electron capture detection.
AB  - The feasibility of developing a single-step clean-up, enrichment procedure for
      organochlorine pesticides (OCPs) in fish tissue samples based on solid-phase
      microextraction (SPME) was investigated. The general analytical methodology
      developed combines conventional solid-liquid extraction of the OCPs from the
      sample using an organic solvent with SPME over the organic extract followed by
      gas chromatography-electron-capture detection (GC-ECD) analysis. Experimental
      SPME conditions such as extraction time, temperature and matrix effects were
      optimised. Under optimised conditions, precision, linearity range, detection
      limits and accuracy were evaluated. Detection limits obtained for fish tissue
      samples were in the range of 0.1-0.7 ng g(-1). Good recoveries (over 70% in all
      cases) were achieved from samples spiked at a concentration level of 10 ng g(-1).
      The accuracy of the developed SPME-GC-ECD procedure in real samples has been
      verified by analysing, using the standard addition method, a certified reference
      material (CRM 430, OCPs in pork fat) with satisfactory results.

PMID- 14584690
TI  - Overloaded gradient elution chromatography on heterogeneous adsorbents in
      reversed-phase liquid chromatography.
AB  - Overloaded band profiles of phenol were measured on a C18-Kromasil column in
      gradient elution conditions. The mobile phase used was a mixture of methanol and
      water. The volume fraction of methanol was allowed to vary between 0 and 0.5. A
      general adsorption model, which expresses the amount of phenol adsorbed q* as a
      function of both its concentration C and the composition phi of the organic
      modifier (methanol) in the mobile phase, was empirically derived from previous
      independent adsorption experiments based on frontal analysis (FA) and frontal
      analysis by the characteristic point (FACP). Accordingly, the general model was
      an extension of the simplest heterogeneous model, the Bilangmuir model, to non
      isocratic conditions. The low-energy sites followed the classical linear solvent
      strength model (LSSM), but not the high-energy sites whose saturation capacity
      linearly decreased with phi. The general model was validated by comparing the
      experimental and simulated band profiles in gradient elution conditions, in
      linear and non-linear conditions, as well. The band profiles were calculated by
      means of the equilibrium-dispersive model of chromatography with a finite
      difference algorithm. A very good agreement was observed using steps gradient
      (delta phi) from 0 to 50% methanol and gradient times t(g) of 20, 25, 30, 40, 60,
      80 and 100 min. The agreement was still excellent for steps gradient from 5 to
      45% (t(g) = 25 min), 5 to 35% (t(g) = 50 min), 5 to 25% (t(g) = 50 min) and 5 to
      15% (t(g) = 50 min). Significative differences appeared between experience and
      simulation when the slope of the gradient (delta phi/t(g)) became too strong
      beyond 3.3% methanol per minute. This threshold value probably mirrored the
      kinetic of arrangement of the G18-bonded chains when the methanol content
      increased in the mobile phase. It suggested that the chromatographic system was
      not in a full thermodynamic equilibrium state when very steep mobile phase
      gradients were applied.

PMID- 14584691
TI  - Improved apparatus for solid-liquid multi-stage counter-current extraction.
AB  - An improved apparatus for solid-liquid multi-stage counter-current extraction
      (SLME) was developed. The apparatus has a set of 24 extraction vessels. Each
      extraction vessel unit is composed of a piston-cylinder in which the solid phase
      is placed, and a cup-cylinder in which the liquid phase is set. Of the 24
      extraction vessels, 20 were used for the separation stage, and the other 4 were
      used for the back-extraction stage. (+/-)-Troger's base was selected as a racemic
      model compound for the continuous enantioseparation by the apparatus, and a
      cellulose derivative was used as the chiral separator. After 50 cycles of the
      operation (in 9 h), 0.1 g of (-)-enantiomer (85% in purity) was recovered from
      the solid phase by back-extraction with ethanol, whereas 1.1 g of (+)-isomer (75%
      in purity) was collected from the liquid phase (ethanol).

PMID- 14584692
TI  - Improved spiral disk assembly for high-speed counter-current chromatography.
AB  - The spiral disk for type-J high-speed counter-current chromatography (HSCCC) has
      been improved by placing short segments of PTFE (tetrafluoroethylene) tubing into
      the channel at regular intervals. The best results were obtained with a four
      channel spiral column using 600 spacers, which significantly improved stationary
      phase retention and partition efficiency in both n-butanol-acetic acid-water
      (4:1:5) and poly(ethylene glycol) 1000-dibasic phosphate polymer phase systems.
      Based on these findings, a "bead-chain spiral disk" was designed and its
      performance tested with a type-J HSCCC centrifuge. This new column design
      substantially improved the separation of both dipeptide and protein samples in
      terms of stationary phase retention and partition efficiency.

PMID- 14584693
TI  - Comparison of on-line flow-cell and off-line solvent-elimination interfaces for
      size-exclusion chromatography and Fourier-transform infrared spectroscopy in
      polymer analysis.
AB  - Two commercial liquid chromatography-Fourier-transform infrared spectroscopy
      interfaces (LC-FTIR), viz. a flow cell and a solvent-elimination interface have
      been assessed for use in size-exclusion chromatography (SEC) with respect to
      their chromatographic integrity (i.e. peak asymmetry, chromatographic
      resolution), quantitative and qualitative aspects. A polycarbonate/aliphatic
      polyester (PC/APE) blend and a polycarbonate-co-polydimethylsiloxane (PC-co-PDMS)
      copolymer were selected for the assessment. Both samples were successfully and
      selectively analyzed. The relatively large volume of the flow cell and the
      inherent deposition characteristics of the solvent-elimination interface led to a
      comparable decrease in the chromatographic resolution. The separation of
      oligomers was diminished in comparison with SEC-ultra-violet (UV). However, the
      peak asymmetry was not significantly affected by either interface. For both
      interfaces, a linear relationship was obtained for the FTIR response versus the
      injected concentration. The sensitivity was found to be higher for the solvent
      elimination interface. For the current model compounds, the flow-cell interface
      detection limits are worse. However, the repeatability of flow-cell SEC-FTIR,
      evaluated by means of four SEC-FTIR analyses of polycarbonate, was considerably
      better than for solvent-elimination SEC-FTIR. This is probably due to the well
      defined optical path length of the sample in the flow cell. By spectral
      subtraction, it was very well possible to obtain qualitative (functional group)
      information for compound identification also with flow-cell SEC-FTIR.

PMID- 14584694
TI  - Influence of ionic strength and organic modifier concentrations on
      characterization of aquatic fulvic and humic acids by high-performance size
      exclusion chromatography.
AB  - Aquatic fulvic acid (FA) and humic acid (HA) were characterized by an aqueous
      high-performance size-exclusion chromatography (HPSEC) using a hydrophilic
      polymeric stationary phase and an aqueous eluent at neutral pH and low-ionic
      strength (5 mM Na2HPO4; final ionic strength, 13 mM). Employed HPSEC showed low
      sensitivity of FA to variations in ionic strength (13 and 100 mM) and contents of
      organic modifier (0.1 or 40% methanol) in aqueous eluent. Under these analytical
      conditions, peak maxima of relative UV signals versus molecular mass (Mr) defined
      as M'p and peak maxima of relative mass concentrations versus Mr defined as Mp of
      FA were shown to be located at 548-690 and 500, respectively. Organic modifier
      concentrations of 40% methanol in aqueous eluent enabled not only analysis of FA,
      but also analysis of some aquatic HA by HPSEC. Analysis showed M'p and Mp values
      of aquatic HAs around 1000 and 600, respectively. Measured molecular mass data of
      FA were found to be consistent with the recently published data describing low
      molecular masses of FA. Results recommend the use of the described HPSEC as a
      simple, rapid, reproducible, low-cost method giving consistent molecular
      sizes/masses of FA and some aquatic HAs.

PMID- 14584695
TI  - Migration of lubricants from food packagings. Screening for lipid classes and
      quantitative estimation using normal-phase liquid chromatographic separation with
      evaporative light scattering detection.
AB  - A normal-phase high-performance liquid chromatography (NP-HPLC) method is
      introduced for the identification and quantitative estimation of 12 lipid classes
      (paraffin, wax esters, cholesterol esters, fatty acid methyl esters, triacyl
      glycerols, fatty alcohols, free fatty acids, cholesterol, 1,3-diacyl glycerols,
      1,2-diacyl glycerols, monoacyl glycerols and fatty acid amide) used as
      lubricantsin food packaging materials. The HPLC separation is carried out on a
      LiChrospher Diol (100 A, 5 microm, 125 mm x 3 mm) column with gradient elution
      (isooctane/0.1% acetic acid in tert-butyl methyl ether) and evaporative light
      scattering detection (ELSD). The method has been calibrated with representatives
      of each class in working ranges of about 5-150 mg/l, depending on the lipid
      class. Intra-day variance for all representatives range from 1.9 to 5.1%, inter
      day variances from 7.0 to 26.5% and the limits of detection from 0.79 to 3.65
      mg/l (except for two classes). A simple sample preparation could be established
      for the determination of migrating lubricants obtained from packaging materials
      containing external or internal lubricants. Since the detector response depends
      on the chain length and the degree of saturation, the quantification of a lipid
      class with unknown composition is only semi-quantitative. The amount of migrating
      lubricants from an epoxy-based can coating could be estimated with 0.3 mg/dm2 and
      from a light weight container with 5.5 mg/dm2.

PMID- 14584696
TI  - Application of high-speed counter-current chromatography to the preparative
      separation and purification of baicalin from the Chinese medicinal plant
      Scutellaria baicalensis.
AB  - Baicalin was separated and purified for the first time from the traditional
      Chinese medicinal plant Scutellaria baicalensis Georgi by high-speed counter
      current chromatography. Crude baicalin was obtained by extraction with methanol
      water (70:30, v/v) from S. baicalensis Georgi. The separation was performed in
      two steps with a two-phase solvent system composed of n-butanol-water (1:1, v/v),
      in which the lower phase was used as the mobile phase at a flow-rate of 1.0 ml
      min(-1) in the head-to-tail elution mode. A total of 37.0 mg of baicalin at 96.5%
      purity was yielded from 200 mg of the crude baicalin (containing 21.6% baicalin)
      with 86.0% recovery as determined by HPLC analysis.

PMID- 14584697
TI  - Preparative separation of rhein from Chinese traditional herb by repeated high
      speed counter-current chromatography.
AB  - High-speed counter-current chromatography (HSCCC) was repeatedly used for
      isolation and purification of rhein from Rheum officinale Baill (Dahuang) with a
      two-phase solvent system composed of n-hexane-ethyl acetate-methanol-water
      (3:7:5:5, v/v), which had been selected by analytical (HSCCC). Using two
      preparative units of the HSCCC centrifuge, about a 500 mg amount of the crude
      extract was separated, yielding 6.7 mg of rhein at a high purity of over 97%.

PMID- 14584698
TI  - Analysis of natural gas: the necessity of multiple standards for calibration.
AB  - The importance of natural gas as an international trading commodity and the cost
      to consumers has made the accuracy of determinations for the components of
      natural gas very important. Pricing of natural gas is based on the heating value
      of the gas determined from either calorimetry measurements or calculations based
      on individual component concentrations determined by gas chromatography (GC). Due
      to the expense of accurate calibration standards, many analysts and laboratories
      will use a single calibration standard to perform natural gas determinations.
      Therefore, the purpose of this study was to determine whether an analyst could
      accurately measure the components of natural gas, in particular methane, using a
      single standard, or whether a suite of standards is necessary to calibrate the
      analytical instrument. A suite of eight gravimetric primary standards was
      prepared covering a concentration range for methane of 64-94 mol%, with
      uncertainties of +/-0.05% relative (95% confidence interval). These natural gas
      primary standards also contained nitrogen, carbon dioxide, ethane, propane, iso
      butane, n-butane, iso-pentane, n-pentane, and n-hexane with varying
      concentrations from 0.02 to 14%. A single analytical method was used in which
      only the amount of sample injected onto the column was altered. The results show
      that when injecting a 0.5 ml sample volume a second-order regression through the
      standards is necessary for the determination of methane. The results for
      nitrogen, ethane and propane also show the same trend. Only those individual
      standards whose methane concentration is within 1% of the test mixture predicted
      a concentration within 0.05% of the regression value. Those individual primary
      standards whose methane concentration is different by more than +/-1% of the test
      mixture predicted values differing by +/-0.5 to +/-2.0% from the regression
      value. These differences lie well outside the predicted concentration uncertainty
      interval of +/-0.20%. A smaller sample volume, 0.1 ml, resulted in a set of data
      that could be fit using linear regression. Each of the eight primary standards
      individually predicted the methane in the test mixture to be within +/-0.11% of
      the predicted value from linear regression. The data confirm that it is
      imperative to fully characterize the analytical system before proceeding with an
      analysis.

PMID- 14584699
TI  - Quantitative analysis of 2-furfural and 5-methylfurfural in different Italian
      vinegars by headspace solid-phase microextraction coupled to gas chromatography
      mass spectrometry using isotope dilution.
AB  - A new method was developed for the determination of 2-furfural (2-F) and 5
      methylfurfural (5-MF), two products of Maillard reaction in vinegar, with head
      space solid-phase microextraction (HS-SPME) coupled to gas chromatography-mass
      spectrometry (GC-MS). A divinylbenzene (DVB)/carboxen (CAR)/polydimethylsiloxane
      (PDMS) fibre was used and SPME conditions were optimised, studying ionic strength
      effect, temperature effect and adsorption time. Both analytes were determined by
      calibration established on 2-furfural-d4 (2-F-d4). The method showed good
      linearity in the range studied (from 16 to 0.12 mg/l), with a regression
      coefficient r2 of 0.9999. Inter-batch precision and accuracy were found between
      14.9 and 6.0% and between -11.7 and 0.2%, respectively. Detection limit was 15
      microg/l. The method is simple and accurate and it has been applied to a series
      of balsamic and non-balsamic vinegars.

PMID- 14584700
TI  - Gas chromatography-mass spectrometry method for determining the methanol and
      acetic acid contents of pectin using headspace solid-phase microextraction and
      stable isotope dilution.
AB  - A simple, fast, and direct procedure was developed for the simultaneous
      determination of the methanol and acetic acid present as esters in the plant cell
      wall polysaccharide pectin. After base-hydrolysis of esters and acidification of
      pectin samples, headspace solid-phase microextraction (SPME) was performed using
      a Carboxen-PDMS fiber assembly. Methanol and acetic acid were separated by gas
      chromatography with a Chrompak PoraPlot Q capillary column and detected using
      electron impact mass spectrometry with selected ion monitoring. Stable deuterated
      isotopomers (d3-methanol and d3-acetic acid) were used as internal standards and
      for constructing calibration curves, providing accurate and absolute
      quantification of analytes. The methanol and acetic acid contents in 1 mg
      quantities of fruit and vegetable pectins were readily quantified by this
      procedure.

PMID- 14584701
TI  - Analysis of total propionic acid in feed using headspace solid-phase
      microextraction and gas chromatography.
AB  - A method is described to analyze total propionic acid content (free propionic
      acid + sodium, ammonium, calcium salts, etc.) in feed, using headspace solid
      phase microextraction (HS-SPME) of a feed suspension in salted and acidified
      water. Optimization of the extraction variables was done by simplex method after
      choosing a polyacrilate fiber to enhance the response of this acid. Separation
      was made by capillary gas chromatography (GC), using a special free fatty acid
      phase (FFAP) column for acids and a flame ionization detector (FID). Some of the
      chromatograms were also done, injecting the SPME fiber in a GC-mass spectrometry
      (MS) system, working with some specific ions for propionic acid, to be selective
      enough to avoid confusing the propionic acid peak with interferences of those
      complex matrixes. The method was tested for linearity and repeatability.
      Detection and quantification limits were also calculated. The method was applied
      to commercial feed samples, very variable in composition, quantifying by standard
      addition method. No major interferences were observed.

PMID- 14584702
TI  - Quantitation of estrogens in ground water and swine lagoon samples using solid
      phase extraction, pentafluorobenzyl/trimethylsilyl derivatizations and gas
      chromatography-negative ion chemical ionization tandem mass spectrometry.
AB  - A method was developed for the confirmed identification and quantitation of
      17beta-estradiol, estrone, 17alpha-ethynylestradiol and 16alpha-hydroxy-17beta
      estradiol (estriol) in ground water and swine lagoon samples. Centrifuged and
      filtered samples were extracted using solid-phase extraction (SPE), and extracts
      were derivatized using pentafluorobenzy] bromide (PFBBR) and N
      trimethylsilylimidazole (TMSI). Analysis was done using negative ion chemical
      ionization (NICI) gas chromatography-mass spectrometry-mass spectrometry (GC-MS
      MS). Deuterated analogs of each of the estrogens were used as isotope dilution
      standards (IDS) and were added to the samples before extraction. A limit of
      quantitation of 1 ng/l in ground water was obtained using 500 ml of ground water
      sample, 1.0 ml of extract volume and the lowest calibration standard of 0.5
      pg/microl. For a 25 ml swine lagoon sample, the limit of quantitation was 40
      ng/l. The average recovery of the four estrogens spiked into 500 ml of distilled
      water and ground water samples (n = 16) at 2 ng/l was 103% (S.D. 14%). For 25 ml
      of swine lagoon samples spiked at 500, 1000 and 10,000 ng/l, the average recovery
      for the four estrogens was 103% (S.D. 15%). The method detection limits (MDLs) of
      the four estrogens spiked at 2 ng/l in a 500 ml of ground water sample ranged
      from 0.2 to 0.6 ng/l. In swine lagoon samples from three different types of swine
      operations, estrone was found at levels up to 25,000 ng/l, followed by estriol
      and estradiol up to levels at 10,000 and 3000 ng/l, respectively. It was found
      that pretreatment of swine lagoon samples with formaldehyde was necessary to
      prevent conversion of estradiol to estrone.

PMID- 14584703
TI  - Fast analysis of nicotine related alkaloids in tobacco and cigarette smoke by
      megabore capillary gas chromatography.
AB  - A novel fast megabore capillary gas chromatographic (MCGC) method for analysis of
      7 nicotine related alkaloids in tobacco and cigarette smoke, including nicotine,
      nornicotine, myosmine, nicotyrine, anabasine, anatabine and 2,3-dipyridyl, was
      developed. The use of megabore capillary column GC methodology, equipped with
      flame ionization detector (FID), provided rapid, unambiguous nicotine related
      alkaloids analysis. One gram flue-cured tobacco (or Cambridge filter pad), 20 ml
      ether, and 5 ml 10% sodium hydroxide solution, added with n-heptadecane as the
      internal standard, were placed in a flask, and the flask was capped and placed in
      an ultrasonic bath for 15 min. A 1 microl volume was analyzed by capillary GC
      operating in split-injection mode on a mega bore Simplicity-5 column. This simple
      procedure was compared with the previously reported packed column GC method and
      the Griffith still-colorimetric method. The application of the method for
      analysis of various flue-cured tobaccos and cigarette smoke was discussed.

PMID- 14584704
TI  - Analytical methods for phenyltin compounds in polychlorinated biphenyl-based
      transformer oil samples.
AB  - We present the first study on the analytical methods of phenyltin compounds (PTs)
      in polychlorinated biphenyl (PCB)-based transformer oil samples. Tetraphenyltin
      (TePhT) has been used as stabilizer for some kinds of PCBs-based transformer oil
      formulations. Monophenyltin (MPhT), diphenyltin (DPhT) and triphenyltin (TrPhT)
      could have been formed from TePhT during long-term use. TePhT was directly
      measured by gas chromatograph (GC) connected with three types of detectors, a
      mass spectrometer (MS), a flame photometric detector (FPD) and an atomic emission
      detector (AED) after dilution with hexane. MPhT, DPhT and TrPhT were propylated
      with Grignard reagent before measurement. The MS was the most sensitive of the
      detectors, with detection limits of phenyltin compounds of 30 ng/ml (MPhT), 9.8
      ng/ml (DPhT), 5.5 ng/ml (TrPhT) and 0.60 ng/ml (TePhT), respectively. From the
      viewpoint of selectivity, MS was slightly worse than other detectors, but
      interference from PCBs matrices was not significant under ordinary analytical
      conditions. Two used transformer oil samples were analyzed using the analytical
      methods developed in this study. TePhT and TrPhT were found in both samples.

PMID- 14584705
TI  - Truffle aroma characterization by headspace solid-phase microextraction.
AB  - In the present study, a headspace solid-phase microextraction (HS-SPME) combined
      to gas chromatography-mass spectrometry (GC-MS) has been used to fully
      characterize aroma of truffles of different species. A fiber of medium polarity
      (for flavors) was used to avoid discrimination towards very non-polar and polar
      volatile compounds. In a previous work, extraction conditions were optimized by
      means of an experimental design leading to the following conditions that were
      used in the present study: extraction temperature, 53 degrees C; extraction time,
      13.6 min; and equilibrium time, 5 min. A comparison among different truffles
      species has been established in terms of qualitative and quantitative differences
      on volatile composition. By using the optimal extraction conditions and GC-MS it
      was possible to identify 89 compounds in two different truffle species such as
      Tuber aestivum and Tuber melanosporum. An attempt has been made in order to be
      able to determine the influence of different geographical origins on the aroma
      fraction of such fungi.

PMID- 14584706
TI  - Light-emitting diode-based indirect fluorescence detection for simultaneous
      determination of anions and cations in capillary electrophoresis.
AB  - This report presents simultaneous analysis of cations and anions by capillary
      electrophoresis (CE) in conjunction with indirect fluorescence detection using a
      blue light-emitting diode (LED), based on the displacement of fluorescein with
      anionic EDTA-metal complexes and anions. A new focusing system combined with a
      plastic lens and a 40x objective was developed and used effectively to focus the
      diverging beam of the LED on the capillary. The optimum compositions for
      simultaneous analysis of metal ions and anions are the samples prepared in 5 mM
      borate, pH 9.2, containing 2 mM EDTA and the background electrolytes (BGEs)
      consisting of 5 mM borate buffer, 5 microM fluorescein, and 1 microM NaCl at pH
      9.2. Using this pre-capillary complexation method, the analysis of a sample
      containing five metal ions and eight anions was accomplished in 8 min, with the
      relative standard deviation values for the migration times less than 2.0%. The
      peak heights against the concentrations of the metal ions and anions are linear
      in 10-1000 and 50-2000 microM, with correlation coefficients better than 0.998,
      and 0.982, respectively. The limits of detection at a signal-to-noise ratio 3 of
      up to 14.6 microM for formate and as low as 3.7 microM for Ni2+. The results of
      the analyses of pond water and a Chinese herbal soup present the advantages of
      this method, including simplicity, rapidity, reproducibility, and low costs.

PMID- 14584707
TI  - Liquid chromatographic separation of derivatives of diospyrin, a bioactive
      bisnaphthoquinonoid plant-product, and analogous naphthyl compounds.
AB  - Isocratic reversed-phase liquid chromatography (LC) method was developed using
      acetonitrile and water for the determination of diospyrin, a pharmacologically
      important bisnaphthoquinonoid plant-product. The method was validated for
      precision, accuracy and reproducibility, and was found to be linear over the
      concentration range of 1-1000 microg/ml; the limits of detection and quantitation
      were 8 and 20 ng, respectively. The technique was used to determine the amount of
      diospyrin in plant extracts from four climatic regions in India. It was also
      applied for differentiation and separation of 27 naphthyl compounds. While a
      composition of 50:50 was preferable for dimeric compounds, the composition 40:60
      was a better choice for the monomers. Also, the isomeric alpha- and beta
      naphthols and their dimers could be distinguished by conversion into the
      respective methyl ethers.

PMID- 14584708
TI  - Optimization of the principal parameters for the ultrarapid electrophoretic
      separation of reduced and oxidized glutathione by capillary electrophoresis.
AB  - Several factors can influence the analytical efficiency and rapidity of the
      quantitative determination of erythrocyte glutathione by capillary zone
      electrophoresis (CZE). We optimized the time, efficiency and resolution of the
      electrophoretic separation of reduced (GSH) and oxidized (GSSG) glutathione by
      studying the influence of the most important factors affecting the separation,
      i.e. the pH and ionic strength of the electrolyte solution, the capillary length
      and temperature. Best results in the shortest time are obtained at 25 degrees C,
      using an uncoated 37 cm x 75 microm i.d. capillary and a 300 mmol/l borate buffer
      pH 7.8. These conditions give a good reproducibility of the corrected peak areas
      (R.S.D. 1.41 and 1.31%) and of the migration time (R.S.D. 0.22 and 0.26%) for GSH
      and GSSG, respectively. The high concentration buffer, besides permitting a good
      resolution of standard GSH and GSSG mix, allows also N-nitrosoglutathione
      detection. By shortening the capillary length to 27 cm, the separation time of
      GSH and GSSG can be further decreased to less than 60s. This shortened method,
      the most rapid described in literature, can detect and quantify GSH in red blood
      cells despite a loss of sensitivity. To compare the new method here described
      with the Beutler colorimetric method, the data relative to the GSH content of red
      blood cells from young normal subjects were analyzed by the Passing and Bablok
      regression and the Bland-Altman test.

PMID- 14584710
TI  - Data-driven analysis strategies for proportion studies in adaptive group
      sequential test designs.
AB  - Using multistage adaptive group sequential test designs, the investigator may
      perform data-driven changes in the design during the course of the trial without
      inflation of the Type I error rate. This is possible, for example, through the
      use of the inverse normal method of combining the p-values from the separate
      stages of the trial. Generally, conditional error functions are useful
      instruments for midtrial design modifications of clinical trials. Particularly,
      it is worthwhile to consider sample size reassessment strategies based on
      conditional power arguments. In this paper, approximate techniques will be
      proposed for the application of the inverse normal combination testing principle
      in superiority and noninferiority proportion studies. Planning facilities and the
      adaptive analysis strategies will be discussed in terms of the Type I error rate,
      the necessary sample size, and the power within the adaptive design. Furthermore,
      how to calculate confidence intervals and overall p-values will be shown.

PMID- 14584711
TI  - An adaptive approach to implementing bivariate group sequential clinical trial
      designs.
AB  - In clinical trials, situations often arise where more than one response from each
      patient is of interest; and it is required that any decision to stop the study be
      based upon some or all of these measures simultaneously. Theory for the design of
      sequential experiments with simultaneous bivariate responses is described by
      Jennison and Turnbull (Jennison, C., Turnbull, B. W. (1993). Group sequential
      tests for bivariate response: interim analyses of clinical trials with both
      efficacy and safety endpoints. Biometrics 49:741-752) and Cook and Farewell
      (Cook, R. J., Farewell, V. T. (1994). Guidelines for monitoring efficacy and
      toxicity responses in clinical trials. Biometrics 50:1146-1152) in the context of
      one efficacy and one safety response. These expositions are in terms of normally
      distributed data with known covariance. The methods proposed require
      specification of the correlation, rho between test statistics monitored as part
      of the sequential test. It can be difficult to quantify rho and previous authors
      have suggested simply taking the lowest plausible value, as this will guarantee
      power. This paper begins with an illustration of the effect that inappropriate
      specification of rho can have on the preservation of trial error rates. It is
      shown that both the type I error and the power can be adversely affected. As a
      possible solution to this problem, formulas are provided for the calculation of
      correlation from data collected as part of the trial. An adaptive approach is
      proposed and evaluated that makes use of these formulas and an example is
      provided to illustrate the method. Attention is restricted to the bivariate case
      for ease of computation, although the formulas derived are applicable in the
      general multivariate case.

PMID- 14584712
TI  - A decision rule for evaluating several independent clinical trials collectively.
AB  - Usually, in applying for market approval of a new drug, more than one similarly
      designed clinical trial is conducted to support efficacy claims. How to evaluate
      these trials collectively and assess the overall type I error of a decision rule
      can be a challenging statistical issue. In this paper, we propose a decision rule
      to collectively evaluate p-values from several similarly designed and
      independently conducted trials. A concept of overall hypotheses, which is
      essentially union or intersection combinations of individual trials' hypotheses,
      is used so that the overall type I error can be controlled at desired levels. We
      also discuss some important properties of the approach, including the selection
      of the overall type I error rates and power. Examples are presented.

PMID- 14584713
TI  - Issues of simultaneous tests for noninferiority and superiority.
AB  - In simultaneous testing for noninferiority and superiority, Morikawa and Yoshida
      (Morikawa, T., Yoshida, M. (1995). A useful testing strategy in phase III trails:
      Combined test of superiority and test of equivalence. J. Biopharmaceutical
      Statistics 5:297-306) argue that multiplicity adjustment is not necessary by
      using the closed testing (CT) principle. In fact, using the same argument, no
      multiplicity adjustment is necessary in simultaneous testing of any number of
      nested null hypotheses. However, simultaneous testing of many nested null
      hypotheses is problematic in a confirmatory trial because such simultaneous
      testing is similar to post-hoc specification of the null hypothesis. Thus,
      simultaneous testing for noninferiority and superiority may be viewed as an
      initial step towards exploratory analysis and may be best used cautiously in
      confirmatory evaluation.

PMID- 14584714
TI  - Protocol designed subgroup analyses in multiarmed clinical trials: multiplicity
      aspects.
AB  - Subgroup analyses are quite common in clinical trials although the subgroup
      findings are usually presented without adjustment for the multiple analyses,
      which increases the chance of false positive findings. This paper is focused on
      the multiplicity aspects of subgroup analyses in multiarmed randomized clinical
      trials and provides some guidance to practitioners.

PMID- 14584715
TI  - Comparison of methods for estimating the number of true null hypotheses in
      multiplicity testing.
AB  - When a large number of statistical tests is performed, the chance of false
      positive findings could increase considerably. The traditional approach is to
      control the probability of rejecting at least one true null hypothesis, the
      familywise error rate (FWE). To improve the power of detecting treatment
      differences, an alternative approach is to control the expected proportion of
      errors among the rejected hypotheses, the false discovery rate (FDR). When some
      of the hypotheses are not true, the error rate from either the FWE- or the FDR
      controlling procedure is usually lower than the designed level. This paper
      compares five methods used to estimate the number of true null hypotheses over a
      large number of hypotheses. The estimated number of true null hypotheses is then
      used to improve the power of FWE- or FDR-controlling methods. Monte Carlo
      simulations are conducted to evaluate the performance of these methods. The
      lowest slope method, developed by Benjamini and Hochberg (2000) on the adaptive
      control of the FDR in multiple testing with independent statistics, and the mean
      of differences method appear to perform the best. These two methods control the
      FWE properly when the number of nontrue null hypotheses is small. A data set from
      a toxicogenomic microarray experiment is used for illustration.

PMID- 14584716
TI  - Industry, government, and academic panel discussion on multiple comparisons in a
      "real" phase three clinical trial.
AB  - A Food and Drug Administration (FDA)/Industry/Academic Panel Discussion on
      multiplicity aspects of a real Phase III clinical trial was held at the Third
      International Conference on Multiple Comparisons, August 6, 2002, in Bethesda,
      Maryland. The goal was to develop some consensus among industry, government, and
      academic statisticians concerning requirements and methods for multiplicity
      management in typical clinical trials. The session was tape-recorded; this
      article mostly comes from an edited transcript.

PMID- 14584717
TI  - Efficacy evaluation under type II censored plan with postclassified samples.
AB  - The main theme of this paper is efficacy evaluation under Type II censoring.
      Observations from a clinical trial are often postclassified into two groups in an
      effort to properly assess the efficacy of an intervention on each group. Thus,
      the numbers of observed lifetimes in the two groups are random outcomes.
      Parameter estimation and hypotheses testing under this postclassified setting are
      discussed. A numerical study is conducted to assess whether the results derived
      based on fixed sample sizes could be used in the postclassified case. The results
      would provide insight to practitioners in analyzing data observed under the
      postclassified case.

PMID- 14584718
TI  - Bayesian approach to average bioequivalence using Bayes' factor.
AB  - In recent years, bioavailability studies for assessment of bioequivalence between
      two or more drug formulations have become very popular in drug development.
      However the current practice for the assessment of bioequivalence suffers from
      certain serious drawbacks. For example, sometimes these tests fail to control the
      consumer's risk. In this article a new methodology based on the application of
      Bayes' factor for solving the average bioequivalence problem is proposed. We
      compare our approach with the existing methods by using real data sets from the
      Food and Drug Administration (FDA). Results are further explored using simulation
      studies.

PMID- 14584719
TI  - Sample size determination based on rank tests in clinical trials.
AB  - The problem of sample size determination based on three commonly used non
      parametric rank based tests, namely, one-sample Wilcoxon's rank sum test, two
      sample's Wilcoxon's rank sum test, and the rank-based test for independence is
      studied. Explicit formulas for variabilities of the test statistics under the
      alternative hypotheses are derived. Consequently, close forms of power functions
      of these test statistics are obtained for sample size determination utilizing the
      concept of higher order polynominal equations. Simulation studies were performed
      to evaluate the finite samples performance of the derived sample size formulas.
      The results indicates that the derived methods work well with moderate sample
      size.

PMID- 14584720
TI  - Using graphical displays of exact overall significance levels as a guideline for
      choosing a significance level for pairwise comparisons of a dichotomous variable.
AB  - Exact overall significance levels for selected sample sizes and response
      probabilities are graphically displayed when a dichotomous variable is compared
      between a placebo and two or more active treatments. A Z-statistic with a pooled
      variance estimator is used as the test statistic and critical values are based on
      the (1 - alpha/2)th percentile of the standard normal distribution. These figures
      are used as a simple guideline for choosing significance levels that achieve a
      desired overall significance level. If an overall significance level of 0.05 is
      desired when comparing a placebo to two, three, or four active treatments, the
      recommended significance levels to be used for each of the two, three, or four
      pairwise comparisons are 0.027, 0.019, or 0.015. If an overall significance level
      of 0.10 is desired, the corresponding recommended significance levels are 0.055,
      0.039, or 0.031.

PMID- 14584721
TI  - Bayesian analysis of a multivariate null intercept errors-in-variables regression
      model.
AB  - Longitudinal data are of great interest in analysis of clinical trials. In many
      practical situations the covariate can not be measured precisely and a natural
      alternative model is the errors-in-variables regression models. In this paper we
      study a null intercept errors-in-variables regression model with a structure of
      dependency between the response variables within the same group. We apply the
      model to real data presented in Hadgu and Koch (Hadgu, A., Koch, G. (1999).
      Application of generalized estimating equations to a dental randomized clinical
      trial. J. Biopharmaceutical Statistics 9(1):161-178). In that study volunteers
      with preexisting dental plaque were randomized to two experimental mouth rinses
      (A and B) or a control mouth rinse with double blinding. The dental plaque index
      was measured for each subject in the beginning of the study and at two follow-up
      times, which leads to the presence of an interclass correlation. We propose the
      use of a Bayesian approach to model a multivariate null intercept errors-in
      variables regression model to the longitudinal data. The proposed Bayesian
      approach accommodates the correlated measurements and incorporates the
      restriction that the slopes must lie in the (0, 1) interval. A Gibbs sampler is
      used to perform the computations.

PMID- 14584722
TI  - Exploring the relationship between surrogates and clinical outcomes: analysis of
      individual patient data vs. meta-regression on group-level summary statistics.
AB  - There has been an increasing interest in exploring the relationship between a
      surrogate and a clinical outcome. Two different statistical approaches have been
      taken by researchers to quantify the treatment effect on the clinical outcome
      explained by the surrogate endpoint: 1) analysis based on individual patient data
      (IPD), and 2) meta-regression based on summary statistics from published
      literature. An analysis based on IPD models the associations between the
      surrogate and clinical outcome for patients directly and is able to adjust for
      patient-level covariates. A meta-regression models the trial-level associations
      using group-level summary statistics and trial-level covariates. The results from
      these two approaches can be quite disparate and researchers may reach different
      conclusions on scientific questions that they wish to answer. We demonstrate that
      the typical summary statistics, such as group means and event counts, do not
      provide a set of sufficient statistics for estimating the underlying relationship
      between the surrogate and clinical outcome for patients. Consequently, the
      associations derived from meta-regression do not necessarily reflect the causal
      relationship for patients and should be interpreted with caution. A meta-analysis
      of antiresorptive agents for osteoporosis serves to illustrate the magnitude of
      differences between the two approaches.

PMID- 14584723
TI  - A group sequential approach to evaluation of bridging studies.
AB  - The International Conference on Harmonization (ICH) E5 guideline defines a
      bridging study as a supplementary study conducted in the new region to provide
      pharmacodynamic or clinical data on efficacy, safety, dosage, and dose regimen to
      allow extrapolation of the foreign clinical data to the population of the new
      region. Therefore, a bridging study is usually conducted in the new region only
      after the test product has been approved for commercial marketing in the original
      region due to its proven efficacy and safety. The issue of analysis of clinical
      data generated by the bridging study conducted in the new region to evaluate the
      similarity for extrapolation of the foreign clinical data to the population of
      the new region is the information on efficacy, safety, dosage, and dose regimen
      of the original region that cannot be concurrently obtained from the local
      bridging studies but is available in the trials conducted in the original region.
      A group sequential approach is therefore proposed to overcome the issue of
      internal validity. In particular, we use the region as a group sequence to enroll
      the patients from the original region first and then to enroll patients from the
      new region subsequently. Methods for sample size determination for the bridging
      study in the new region are also proposed.

PMID- 14584724
TI  - Selfishness in moderation: evolutionary success of the yeast plasmid.

PMID- 14584726
TI  - Regulation of chromatin structure and gene activity by poly(ADP-ribose)
      polymerases.

PMID- 14584725
TI  - Nongenomic actions of androgen in Sertoli cells.
AB  - Nongenomic actions mediated by androgens have now been described in more than 10
      cell types. Some of these cells transduce androgen signals using surface
      receptors that await final characterization, whereas other cells employ the
      classical AR. Various second messengers can be activated by androgens, including
      cAMP, IP3, phospholipase C, DAG, and Ca2+. Each of these second messengers is
      capable of activating multiple kinases. One of the most important kinase networks
      to be regulated by androgens is the MAP kinase cascade. This series of kinase
      reactions is capable of altering the activity of many transcription factors with
      important implications for the regulation of gene expression. Because there is
      evidence that androgen is capable of regulating CREB-mediated gene expression via
      the MAP kinase pathway, it is now somewhat misleading to characterize androgen
      actions in Sertoli cells as nongenomic. Instead, it may be more appropriate to
      label these activities as independent of AR-DNA interactions, or more simply as
      nonclassical. The nonclassical regulation of gene expression in Sertoli cells is
      particularly relevant for providing an answer to the paradox of how testosterone
      can support spermatogenesis yet regulate few genes via AR-promoter interactions.
      It is expected that with the increasing use of microarray and related
      technologies, additional AR-regulated genes will be identified. However, the
      androgen-induced increases in [Ca2+]i, the activation of Src kinase, and the MAP
      kinase cascade that have been characterized thus far have the potential to
      regulate the expression of many more genes than is possible by direct AR-promoter
      interactions. Thus, it is likely that nonclassical actions of testosterone in
      Sertoli cells will be found to be a necessary complement to the classical actions
      that are required to maintain spermatogenesis.

PMID- 14584727
TI  - Centrosomes and kinetochores, who needs 'Em? The role of noncentromeric chromatin
      in spindle assembly.

PMID- 14584728
TI  - Modeling cardiogenesis: the challenges and promises of 3D reconstruction.

PMID- 14584729
TI  - Plasmid and chromosome traffic control: how ParA and ParB drive partition.

PMID- 14584730
TI  - Disease spillover woes.

PMID- 14584731
TI  - FDA seeks to clear up confusion about compounding.

PMID- 14584732
TI  - Additional comments on personality testing issue.

PMID- 14584734
TI  - Zoonosis update on campylobacteriosis stirs debate.

PMID- 14584733
TI  - Zoonosis update on campylobacteriosis stirs debate.

PMID- 14584735
TI  - Wants mention of diets fed to cats with lower urinary tract disease.

PMID- 14584736
TI  - Another interpretation of ferret's reaction to vaccination.

PMID- 14584737
TI  - A shared thought on animal health.

PMID- 14584738
TI  - What is your diagnosis? Esophageal obstruction.

PMID- 14584739
TI  - Animal behavior case of the month. Urine marking.

PMID- 14584740
TI  - Selection of a veterinarian by US pet-owning households.

PMID- 14584741
TI  - Sporotrichosis.

PMID- 14584742
TI  - Taurine deficiency in Newfoundlands fed commercially available complete and
      balanced diets.
AB  - OBJECTIVE: To determine taurine status in a large group of Newfoundlands related
      by environment, diet, or breeding to a dog with dilated cardiomyopathy and
      taurine deficiency. DESIGN: Prospective study. ANIMALS: 19 privately owned
      Newfoundlands between 5 months and 11.5 years old that had been fed commercial
      dry diets meeting established nutrient recommendations. PROCEDURE: Diet histories
      were obtained, and blood, plasma, and urine taurine concentrations and plasma
      methionine and cysteine concentrations were measured. In 8 dogs, taurine
      concentrations were measured before and after supplementation with methionine for
      30 days. Ophthalmic examinations were performed in 16 dogs; echocardiography was
      performed in 6 dogs that were taurine deficient. RESULTS: Plasma taurine
      concentrations ranged from 3 to 228 nmol/mL. Twelve dogs had concentrations < 40
      nmol/mL and were considered taurine deficient. For dogs with plasma
      concentrations < 40 nmol/mL, there was a significant linear correlation between
      plasma and blood taurine concentrations. For dogs with plasma concentrations > 40
      nmol/mL, blood taurine concentrations did not vary substantially. Taurine
      deficient dogs had been fed lamb meal and rice diets. Retinal degeneration,
      dilated cardiomyopathy, and cystinuria were not found in any dog examined for
      these conditions. The taurine deficiency was reversed by a change in diet or
      methionine supplementation. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate
      a high prevalence of taurine deficiency among an environmentally and genetically
      related cohort of Newfoundlands fed apparently complete and balanced diets. Blood
      taurine concentrations indicative of taurine deficiency in Newfoundlands may be
      substantially less than concentrations indicative of a deficiency in cats.

PMID- 14584743
TI  - Taurine deficiency in dogs with dilated cardiomyopathy: 12 cases (1997-2001).
AB  - OBJECTIVE: To determine signalment, history, clinical signs, blood and plasma
      taurine concentrations, electrocardiographic and echocardiographic findings,
      treatment, and outcome of dogs with low blood or plasma taurine concentrations
      and dilated cardiomyopathy (DCM). DESIGN: Retrospective study. ANIMALS: 12 client
      owned dogs with low blood or plasma taurine concentrations and DCM. PROCEDURE:
      Medical records were reviewed, and clinical data were obtained. RESULTS: All 12
      dogs were being fed a commercial dry diet containing lamb meal, rice, or both as
      primary ingredients. Cardiac function and plasma taurine concentration improved
      with treatment and taurine supplementation. Seven of the 12 dogs that were still
      alive at the time of the study were receiving no cardiac medications except
      taurine. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that consumption of
      certain commercial diets may be associated with low blood or plasma taurine
      concentrations and DCM in dogs. Taurine supplementation may result in prolonged
      survival times in these dogs, which is not typical for dogs with DCM. Samples
      should be submitted for measurement of blood and plasma taurine concentrations in
      dogs with DCM, and taurine supplementation is recommended while results of these
      analyses are pending.

PMID- 14584744
TI  - Clinicopathologic and radiographic features and etiologic agents in cats with
      histologically confirmed infectious pneumonia: 39 cases (1991-2000).
AB  - OBJECTIVE: To determine clinicopathologic and radiographic features and etiologic
      agents in cats that died as a result of infectious pneumonia. DESIGN:
      Retrospective study. ANIMALS: 39 cats. PROCEDURE: Medical records of cats in
      which infectious pneumonia was confirmed by histologic examination of necropsy
      specimens were reviewed. Signalment, clinical signs, and results of a CBC, viral
      serologic tests, and thoracic radiography were evaluated. Infectious agents were
      classified as bacterial, viral, fungal, protozoal, or parasitic. Histologic
      features (severity, duration, anatomic location, and distribution) were analyzed.
      RESULTS: Clinical signs referable to the respiratory tract were not detected in
      14 of 39 (36%) cats, and results of a CBC (4/18 cats) and radiography (3/13) were
      unremarkable. Sixteen of 39 (41%) cats lacked clinical signs of systemic illness.
      Etiologic agents identified included bacteria (n = 21), viruses (11), fungi (6),
      protozoa (2), and parasites (1). Cats with clinical signs related to the
      respiratory tract (19/24 [79%] cats) were more likely to have severe histologic
      changes than cats without signs related to the respiratory system (6/14). Twenty
      nine of 38 (76%) cats had histologic evidence of systemic disease, whereas the
      remaining cats had lesions limited to the respiratory tract. CONCLUSIONS AND
      CLINICAL RELEVANCE: Infectious pneumonia is uncommon in cats. Cats with
      infectious pneumonia may lack clinical signs and have unremarkable results for a
      CBC and thoracic radiography, yet frequently have systemic infections. Therefore,
      clinicians should maintain an index of suspicion for pneumonia and evaluate the
      respiratory tract when infection is detected in other organ systems.

PMID- 14584745
TI  - Outbreak of rabbit hemorrhagic disease in domestic lagomorphs.
AB  - Rabbit hemorrhagic disease (RHD) was diagnosed in domestic lagomorphs on a rabbit
      farm in Illinois. Clinical signs of RHD in affected rabbits included signs of
      depression, anorexia, fever, paddling, convulsions, and sudden death. Findings of
      necropsies and histologic evaluations of specimens of liver and spleen were
      indicative of RHD. In liver specimens obtained from dead rabbits, RHD viral
      antigen was detected via hemagglutination assay and viral antigen-detection
      ELISA. The source of the outbreak was traced to a rabbitry in Utah. As the
      disease spread, the outbreak involved rabbits in various regions of the United
      States; > 4,800 rabbits were euthanatized and buried as a result of the
      depopulation effort in several states. The economic impact of the disease can be
      considerable; if the disease is suspected, it is imperative that the appropriate
      state or federal veterinarian's office be contacted immediately.

PMID- 14584746
TI  - Intravesicular administration of clotrimazole for treatment of candiduria in a
      cat with diabetes mellitus.
AB  - A 12-year-old spayed female domestic longhair cat developed fungal cystitis
      (Candida sp). The cat had a history of chronic diabetes mellitus,
      hyperadrenocorticism, and bacterial cystitis caused by Escherichia coli.
      Antifungal agents (itraconazole and fluconazole) were administered orally without
      noticeable effect on the candiduria. Because of the ineffectiveness of these
      treatments, intravesicular administration of 1% clotrimazole solution was
      performed weekly for 3 treatments. Complete resolution of urinary candidiasis was
      detected after the third infusion. Intravesicular administration of clotrimazole
      solution appears to be a safe and effective treatment of fungal cystitis in cats.

PMID- 14584747
TI  - Familial aortic aneurysm in Leonberg dogs.
AB  - A thoracic aortic aneurysm was diagnosed in a 6-month-old male Leonberg dog by
      use of radiography, transthoracic and transesophageal echocardiography, and
      magnetic resonance imaging. The aneurysm was associated with a twisted ascending
      aorta and dilatation of several other thoracic arteries (pulmonary trunk,
      brachiocephalic trunk, and left subclavian artery). Histologic examination of the
      aorta revealed cystic medial necrosis, with disruption of the elastic network,
      collagen fibers, and the muscle glycoprotein fibrillin-1. The dam and sire of the
      dog and 8 littermates were examined by use of transthoracic echocardiography. The
      sire and 1 male littermate also had an aneurysm of the ascending aorta. To the
      authors' knowledge, this is the first report of familial aortic aneurysm in dogs.

PMID- 14584748
TI  - Patterns of mycoplasma shedding in the milk of dairy cows with intramammary
      mycoplasma infection.
AB  - OBJECTIVE: To determine patterns of mycoplasma shedding in the milk of dairy cows
      with intramammary mycoplasma infection. DESIGN: Prospective clinical trial.
      ANIMALS: 10 Holstein cows with intramammary mycoplasma infection. PROCEDURE: Milk
      samples were collected from each cow daily for 28 days and plated on mycoplasma
      agar to evaluate shedding patterns. To determine whether enrichment improved
      recovery of organisms, some samples were also inoculated in mycoplasma enrichment
      medium and incubated for 4 days prior to plating. Somatic cell count (SCC) was
      determined in samples collected weekly. RESULTS: Mycoplasma organisms were not
      isolated from 81 of 280 (29%) composite milk samples, but > 10(6) colonies/mL
      were obtained from 151 (54%). Similarly, mycoplasma organisms were not isolated
      from 433 of 1,008 (43%) quarter milk samples, but > 10(6) colonies/mL were
      obtained from 392 (39%). For 71 of 104 (68%) samples, mycoplasma organisms were
      isolated both following direct plating and following enrichment; for 24 of 104
      (23%), mycoplasma organisms were isolated only following enrichment; and for 9 of
      104 (9%), mycoplasma organisms were isolated only after direct plating. There was
      a linear correlation between logarithm of the SCC and logarithm of the number of
      colony-forming units of mycoplasma per milliliter of milk for composite and
      quarter milk samples. CONCLUSIONS AND CLINICAL RELEVANCE: Shedding of organisms
      was inconsistent in dairy cows with intramammary mycoplasma infection, increasing
      the risk of misdiagnosis if multiple milk samples are not tested.

PMID- 14584749
TI  - Minimum alveolar concentration of sevoflurane in spontaneously breathing llamas
      and alpacas.
AB  - OBJECTIVE: To determine the minimum alveolar concentration (MAC) of sevoflurane
      in spontaneously breathing llamas and alpacas. DESIGN: Prospective study.
      ANIMALS: 6 healthy adult llamas and 6 healthy adult alpacas. PROCEDURE:
      Anesthesia was induced with sevoflurane delivered with oxygen through a mask. An
      endotracheal tube was inserted, and a port for continuous measurement of end
      tidal and inspired sevoflurane concentrations was placed between the endotracheal
      tube and the breathing circuit. After equilibration at an end-tidal-to-inspired
      sevoflurane concentration ratio > 0.90 for 15 minutes, a 50-Hz, 80-mA electrical
      stimulus was applied to the antebrachium until a response was obtained (ie, gross
      purposeful movement) or for up to 1 minute. The vaporizer setting was increased
      or decreased to effect a 10 to 20% change in end-tidal sevoflurane concentration,
      and equilibration and stimulus were repeated. The MAC was defined as the mean of
      the lowest end-tidal sevoflurane concentration that prevented a positive response
      and the highest concentration that allowed a positive response. RESULTS: Mean +/-
      SD MAC of sevoflurane was 2.29 +/- 0.14% in llamas and 2.33 +/- 0.09% in alpacas.
      CONCLUSIONS AND CLINICAL RELEVANCE: The MAC of sevoflurane in llamas and alpacas
      was similar to that reported for other species.

PMID- 14584750
TI  - Evaluation of cardiac function in active and hibernating grizzly bears.
AB  - OBJECTIVE: To evaluate cardiac function parameters in a group of active and
      hibernating grizzly bears. DESIGN: Prospective study. ANIMALS: 6 subadult grizzly
      bears. PROCEDURE: Indirect blood pressure, a 12-lead ECG, and a routine
      echocardiogram were obtained in each bear during the summer active phase and
      during hibernation. RESULTS: All measurements of myocardial contractility were
      significantly lower in all bears during hibernation, compared with the active
      period. Mean rate of circumferential left ventricular shortening, percentage
      fractional shortening, and percentage left ventricular ejection fraction were
      significantly lower in bears during hibernation, compared with the active period.
      Certain indices of diastolic function appeared to indicate enhanced ventricular
      compliance during the hibernation period. Mean mitral inflow ratio and isovolumic
      relaxation time were greater during hibernation. Heart rate was significantly
      lower for hibernating bears, and mean cardiac index was lower but not
      significantly different from cardiac index during the active phase. Contrary to
      results obtained in hibernating rodent species, cardiac index was not
      significantly correlated with heart rate. CONCLUSIONS AND CLINICAL RELEVANCE:
      Cardiac function parameters in hibernating bears are opposite to the chronic
      bradycardic effects detected in nonhibernating species, likely because of
      intrinsic cardiac muscle adaptations during hibernation. Understanding mechanisms
      and responses of the myocardium during hibernation could yield insight into
      mechanisms of cardiac function regulation in various disease states in
      nonhibernating species.

PMID- 14584751
TI  - Review: Mitochondrial medicine--cardiomyopathy caused by defective oxidative
      phosphorylation.
AB  - During experimental hypertensive cardiac hypertrophy, the heart energy metabolism
      reverts from the normal adult type that obtains the majority of its requirement
      for adenosine triphosphate (ATP) from metabolism of fatty acids and oxidative
      phosphorylation (OXPHOS), to the fetal form, which metabolizes glucose and
      lactate. Mitochondrial synthesis and function require an estimated 1000
      polypeptides, 37 of which are encoded by mitochondrial (mt) DNA, the rest by
      nuclear (n) DNA. Inherited or acquired aberrations of either mtDNA or nDNA
      mitochondrial genes cause mitochondrial dysfunction. Tissue expression of OXPHOS
      enzyme defects is often heterogeneous. As a result, cardiomyopathy and cardiac
      failure are frequent but unpredictable complications of mitochondrial
      encephalopathy, neuropathy, and myopathy. Several nuclear genes that encode
      mitochondrial proteins have been sequenced and specific defects associated with
      nuclear genes that affect mitochondrial structure and function have been linked
      to hypertrophic and dilated cardiomyopathies and to cardiac conduction defects.
      Thyroid hormone and exercise stimulate expression of a nuclear respiratory factor
      (NRF) that induces the nuclear gene TFAM, which encodes the mitochondrial
      transcription factor A that controls mitochondrial replication and transcription.
      TFAM-null mouse embryos lack mitochondria and fail to develop a heart.
      Mitochondrial dysfunction enhances the generation of radical oxygen species
      (ROS), which damage mtDNA, nDNA, proteins, and lipid membranes. Mice lacking the
      mitochondrial antioxidant enzyme manganese-superoxide dismutase (SOD) develop
      dilated cardiomyopathy. Palliative mitochondrial therapy with L-acetyl-carnitine
      and coenzyme Q10 improves cardiac function in patients with cardiomyopathy. Cure
      is only achievable by mitochondrial gene therapy. Experimental direct gene
      therapy uses vectors or targeting signal sequences to insert genes into mtDNA;
      indirect gene therapy employs viral or non-viral vectors to introduce genes into
      nDNA. Clinical repair of damaged somatic and germline genes that encode
      mitochondrial proteins may soon be within reach.

PMID- 14584752
TI  - Thromboembolic risk factors in patients undergoing kidney transplant: implication
      of abnormally short activated partial thromboplastin time.
AB  - This study was designed to examine the relationship of short activated partial
      thromboplastin time (aPTT) and prothrombin time (PT) to the incidence of
      thromboembolic events, hereditary and acquired coagulation defects associated
      with an increased risk of thrombosis, or cardiovascular diseases in patients
      undergoing renal transplantation. The prevalence of these conditions in our
      patients (n = 436) was 55%. Forty-two percent of the patients had short aPTT or
      PT. Multivariate analysis revealed that patients with short aPTT have an odds
      ratio (OR) = 2.15, 95% Confidence Interval (CI) (1.27-3.64) (p = 0.0042), and for
      patients with short PT, an OR = 2.01, 95% CI (0.99-4.08) (p = 0.052). Our study
      also suggests that other risk factors, including non-white ethnicity (98%
      blacks), OR = 1.64, 95% CI (1.01-2.67) (p = 0.047), diabetes mellitus, OR = 2.62,
      95% CI (1.11-6.18) (P = 0.028), and autosomal dominant polycystic kidney disease
      (ADPKD) (p < 0.0001). Short aPTT results, or probably short PT results, pre- or
      post-transplantation may be associated with increased risks for thromboembolism.

PMID- 14584753
TI  - Laboratory diagnosis of paroxysmal nocturnal hemoglobinuria.
AB  - Paroxysmal nocturnal hemoglobinuria (PNH) is an uncommon acquired stem cell
      disorder associated with periodic hemolytic events. This benign clonal disease is
      caused by abnormalities of the X-linked phosphatidylinositol glycan class A
      (PIGA) gene and is associated with cytopenias and thrombosis. Although the
      trilineage of bone marrow elements is affected, involvement of the red blood cell
      (RBC) line was recognized first due to its abnormal sensitivity to complement
      mediated intravascular hemolysis. Totally or partially deficient blood cell
      membrane proteins include decay accelerating factor (DAF, CD55), membrane
      inhibitor of reactive lysis (MIRL, CD59), and other proteins attached to the
      glycophosphatidylinositol (GPI) spine. Stem cell transplantation can be curative
      in PNH. Diverse laboratory abnormalities observed in PNH include bone marrow
      hyper- and hypoplasia, hematologic cytopenias, micro- and macrocytosis, decreased
      leukocyte alkaline phosphatase (LAP), hemoglobin- and hemosiderinuria, as well as
      associated iron deficiency. The more definitive laboratory tests comprise older
      biochemical and newer flow cytometric (FCM) procedures. The former group includes
      the sucrose hemolysis test for screening and Ham's acid hemolysis test for
      confirmation; the latter group includes FCM analyses of CD55 and CD59, which have
      recently replaced Ham's test, and FCM quantification of specific GPI-anchor
      binding using fluorescent-labeled inactive toxin aerolysin (FLAER). FLAER is more
      sensitive than FCM quantification of antibody-binding to CD59 for PNH diagnosis.

PMID- 14584754
TI  - Erythropoietic activities in acute leukemia and in malignant lymphoma with or
      without bone marrow involvement.
AB  - Erythropoietic activities and immature reticulocyte production were investigated
      in a total of 157 patients (81 men, 76 women, median age = 42 yr, range = 23 to
      65 yr) with acute lymphoid leukemia (ALL, n = 31), acute myeloid leukemia (AML, n
      = 39), or non-Hodgkin's lymphoma (NHL, n = 87), based on assays of the hemogram,
      red cell indices, reticulocyte subpopulations, and intramedullary erythroid
      precursors. There were no significant differences in red blood cell (RBC) counts,
      blood hemoglobin levels, or erythroid precursors between ALL and AML patients.
      Reticulocytes in AML patients averaged 1.7 +/- 0.8%, which was higher than in
      patients with ALL (0.8 +/- 0.3%, p <0.01); the proportion of high-fluorescence
      reticulocytes (HFR) averaged 4-fold higher in AML versus ALL (p <0.01) and the
      reticulocyte maturity index (RMI) was higher in AML (20.8 +/- 8.3%) versus ALL
      (12.4 +/- 6.5%, p <0.01). The RMI was higher in NHL patients with bone marrow
      (BM) involvement (15.6 +/- 9.4%), compared to those without BM involvement (4.3
      +/- 2.1%, p <0.01). The proportion of HFR averaged 11-fold higher in NHL with BM
      involvement versus NHL without BM involvement. In summary, erythropoietic
      activity is significantly more active in patients with AML compared to ALL and in
      patients with NHL with BM involvement, compared to NHL without BM involvement.

PMID- 14584755
TI  - Erythropoietin and the erythropoietin receptor are expressed by papillary thyroid
      carcinoma from children and adolescents. Expression of erythropoietin receptor
      might be a favorable prognostic indicator.
AB  - Erythropoietin (EPO) and the EPO receptor (EPO-R) have been implicated in solid
      tumors of the brain, breast, kidney and female genital tract. Based on their
      expression by a variety of tumors, we hypothesized that EPO and/or EPO-R might be
      expressed by thyroid cancers. To test this, we determined EPO and EPO-R
      expression by immunohistochemistry in 17 papillary thyroid carcinomas (PTC) from
      children and adolescents. Only a minority of PTC (4/17, 24%) expressed EPO, and
      there were no significant differences between the PTC that did or did not express
      EPO. In contrast, EPO-R was detected in the majority of PTC (11/17, 65%). The
      average tumor size (1.5 +/- 0.8 cm), MACIS score (3.6 +/- 0.2) and risk of
      recurrence (0/11) for the EPO-R(+) PTC were significantly less than those for PTC
      that failed to express EPO-R (average tumor size = 3.6 +/- 2.4 cm, p = 0.021;
      average MACIS score = 4.3 +/- 0.7, p = 0.004; recurrence = 3/6, p = 0.029). We
      conclude that the majority of PTC from children and adolescents express EPO-R, a
      finding associated with favorable prognostic indicators and a lower risk of
      recurrence.

PMID- 14584756
TI  - Thyroxine effects on serum insulin-like growth factor I levels, anthropometric
      measures, and body composition in patients after thyroidectomy.
AB  - Thyroxine is an important hormone related to growth. To study the effects of
      thyroxine on serum levels of insulin-like growth factor I (IGF-I), anthropometric
      measures, and body composition, we studied 28 patients who were receiving
      thyroxine therapy after thyroidectomy for well-differentiated thyroid cancer.
      Serum IGF-I levels decreased from 38.3 +/- 19.0 ng/ml (mean +/- SD) to 26.8 +/-
      12.8 ng/ml (p <0.001) after withdrawal of thyroxine and increased to 43.8 +/-
      20.2 ng/ml (p <0.001) after thyroxine was resumed. The serum levels of TSH, T3,
      and thyroxine changed accordingly after withdrawal and resumption of thyroxine
      therapy. Skinfold thickness increased from 21.8 +/- 6.5 mm to 23.7 +/- 6.4 mm (p
      <0.001) after withdrawal of thyroxine and decreased to 21.5 +/- 6.9 mm after
      resumption of thyroxine. Similar changes occurred in the circumferences of the
      waist and hip (p <0.01), but no significant change occurred in arm muscle
      circumference (18.7 +/- 2.3 cm vs 18.7 +/- 2.3 cm vs 19.0 +/- 2.4 cm). Body
      composition analysis by bioelectrical impedance showed no significant changes in
      the percentages of body fat and lean mass. In conclusion, withdrawal of thyroxine
      from patients with thyroid cancer was associated with an immediate decrease in
      serum IGF-I levels. However, lean mass did not respond to the changes in serum
      IGF-I levels.

PMID- 14584757
TI  - Polymorphisms of prostate-specific antigen gene promoter: determination from cord
      blood collected on filter paper.
AB  - Recent studies have shown that a single nucleotide polymorphism of A/G
      substitution in the androgen response element-1 (ARE-1) of the promoter for the
      prostate-specific antigen gene is a biomarker of prostate cancer. Portugese men
      with prostate cancer have a high percentage (43%) of the AA polymorphism of the
      gene (41% AG, 16% GG), whereas healthy Japanese men have a much lower rate (5%)
      of the AA polymorphism, (31% AG, 64% GG). The goal of the present study was to
      see whether or not the Chinese also have a low rate of the AA polymorphism. This
      study used 94 specimens of cord blood that were the leftover waste of cord blood
      banking. The samples were collected from Chinese infants onto filter paper,
      dried, and shipped to Rochester, MN, USA, for PCR amplification and analysis. The
      observed rate of the AA polymorphism in the samples was very low (5%), with 26%
      AG, 69% GG. The low incidence of AA polymorphism appears to be a trait of Asians
      that may reduce their risk of prostate cancer.

PMID- 14584758
TI  - Plasma C-reactive protein levels in severe diabetic ketoacidosis.
AB  - Elevated plasma levels of C-reactive protein (CRP) and IL-6 have been reported to
      be sensitive indicators of infection in adults with diabetic ketoacidosis (DKA).
      However, both CRP and the pro-inflammatory cytokines, which regulate CRP, can be
      elevated without infection. Our hypothesis was that CRP is increased in young
      patients with severe DKA, even in the absence of an infection, and may serve as a
      marker for systemic inflammatory response syndrome (SIRS). In 7 patients with
      severe DKA without infection, we measured plasma CRP, IL-6, IL-1beta and TNF
      alpha levels prior to, during, and following correction of DKA. CRP was
      significantly but transiently elevated in 4 of the patients prior to or during
      treatment of DKA, compared to their baseline values (96 hr after correction of
      DKA). There were significant positive relationships between CRP and both IL-6 and
      IL-1beta prior to treatment (p <0.05); between CRP and IL-6, IL-1beta, and TNF
      alpha at 6 hr (p <0.05); and between CRP and IL-1beta at 24 hr (p <0.05). The
      results support the hypothesis that CRP is increased in some patients by severe
      DKA and its treatment, and that DKA can be associated with a non-infectious form
      of SIRS.

PMID- 14584759
TI  - Reference limits for copper and iron in liver biopsies.
AB  - Using 141 liver biopsy results (103 adults, 38 children) and a rank-order
      approach, the following reference limits were found: copper 55 microg/g dry
      weight, iron 1800 microg/g dry weight (adults only), and iron index 1.0. The
      study was made feasible by the fact that both copper and iron were measured as
      standard practice in every liver biopsy received for either test. The added
      analyte tended to contribute more to normal results. Specimens with elevations of
      both were infrequent (7 of 141) and significant elevations of both (copper >200
      microg/g, iron index >2.0) were suggestive of contamination. Advantages of using
      patient data included studying specimens of limited availability and acquiring
      information on the distribution of elevated results seen in clinical practice.
      Disadvantages included increased uncertainty in the reference limits relative to
      a normal population. Although most of the study population consisted of patients
      referred for diagnosis of Wilson's disease or hemochromatosis, the reference
      intervals were similar to those reported from autopsy studies.

PMID- 14584760
TI  - Hydroxyethyl starch inhibits NF-kappaB activation and prevents the expression of
      inflammatory mediators in endotoxic rats.
AB  - Hydroxyethyl starch (HES) has been shown to be beneficial in several inflammatory
      situations, but the mechanisms are unclear. The present study tested the
      hypothesis that HES has effects on nuclear factor kappa B (NF-kappaB) activation
      and the expression of inflammatory mediators induced by lipopolysaccharide.
      Sepsis was induced in male Wistar rats by injection of lipopolysaccharide (LPS, 6
      mg/kg, i.p.). At 1 min after the LPS challenge, HES was infused via the right
      external jugular vein at the following doses: 3.75, 7.5, 15, or 30 ml/kg. NF
      kappaB activation in peripheral blood mononuclear cells and neutrophils, plasma
      concentrations of tumor necrosis factor (TNF)-alpha, cytokine-induced neutrophil
      chemoattractant (CINC), expression of CD11b on the blood neutrophil cell surface,
      and neutrophil sequestration in multiple organs were examined 2 or 4 hr after the
      LPS challenge. Treatment of rats with HES (3.75 and 7.5 ml/kg) prevented LPS
      induced NF-kappaB activation, and inhibited, in a dose-related manner, LPS
      induced TNF-alpha and CINC expression. The 4 graded doses of HES decreased CD11b
      expression in a dose-dependent manner. HES significantly reduced neutrophil
      sequestration in lung, heart, and liver. These results suggest that HES has an
      anti-inflammatory effect in endotoxic rats. This effect is mediated by inhibition
      in the production pathways for inflammatory mediators, including NF-kappaB
      activation.

PMID- 14584761
TI  - Dehydroepiandrosterone improves hepatic antioxidant systems after renal ischemia
      reperfusion injury in rabbits.
AB  - This study evaluated the effects of dehydroepiandrosterone (DHEA) on the oxidant
      [malondialdehyde (MDA)] and antioxidant [superoxide dismutase (SOD), glutathione
      peroxidase (GPx), catalase (CAT), and glutathione (GSH)] systems in liver after
      renal ischemia-reperfusion (IR) injury in rabbits. Thirty rabbits were randomly
      assigned to 3 groups of 10: group I (sham operation), group II (renal IR group),
      and group III (DHEA, 25 mg/kg, s.c., 15 min pre-ischemia). Renal IR injury in
      group II caused a decrease of SOD (25%), GPx (36%), and CAT (26%) activities and
      GSH levels (32%), and increases of MDA (30%) in liver and of ALT and AST
      activities in serum, compared to group I. DHEA administration decreased the
      hepatic MDA level (19%) and serum ALT activity (30%) (p <0.01 and p <0.05,
      respectively), and considerably increased hepatic GSH levels and GPx activities
      (p <0.01 for both) in group III, compared to group II. These results suggest that
      DHEA treatment has beneficial effects on antioxidant defenses against hepatic
      injury after renal IR in rabbits, possibly by augmenting GSH levels and lowering
      MDA production.

PMID- 14584762
TI  - Mature cystic teratoma of the ovary associated with complete colonic wall and
      mucinous cystadenoma.
AB  - Mature cystic teratomas of the ovary frequently contain intestinal type
      epithelium, but they are rarely associated with complete intestinal wall. The
      association of mature cystic teratoma with mucinous cystadenoma is not unusual.
      However, the pathogenetic relationship between these two lesions remains
      unanswered. We report a mature cystic teratoma of the ovary in a 16-yr old female
      that contained a complete colonic wall in continuity with an endocervical-type
      mucinous cystadenoma. Both the mucinous cystadenoma and the colonic wall showed
      the typical histopathological and immunohistochemical patterns of classical
      mucinous cystadenoma (positive for CK7, negative for CK20) and normal colonic
      wall (positive for CK20, negative for CK7), respectively. The microscopic and
      immunohistochemical patterns of the epithelium from the transitional zone between
      colonic wall-like structure and mucinous cystadenoma demonstrated features of
      both types of epithelium, positive for both CK7 and CK20, and focally positive
      for a neuroendocrine marker, chromogranin, which is normally present in colonic
      mucosa. These results suggest that the mucinous cystadenoma originated from the
      colonic epithelium of the mature cystic teratoma.

PMID- 14584763
TI  - Blood transfusion from antiquity to the discovery of the Rh factor.

PMID- 14584764
TI  - Appendico-cutaneous fistula presenting clinically as right loin necrotizing
      fasciitis: a case report.
AB  - Acute appendicitis and its subsequent complications continue to pose a surgical
      challenge. One such complication, the appendico-cutaneous fistula, represents a
      very rare form of enterocutaneous fistula. Very few cases have been reported thus
      far in the literature. The clinical presentation of this case before the final
      diagnosis was made makes interesting reading. The report describes a unique case
      that presented with the onset of cellulitis around the right lumbar/loin region,
      spreading down the right posterior back to the posterior gluteal area, and
      appearing as necrotizing fasciitis. There were no abdominal signs at all. The
      patient was then taken to the operating room (OR) for incision and drainage
      through a right flank incision, which could be extended. At drainage, there was a
      feculent smell with discharge that immediately raised the possibility of colonic
      connection with the abscess cavity. Swab sent for culture and sensitivity grew E.
      coli and Bacteroides. The final diagnosis proved to be a perforated appendix.
      Therefore, perforated appendix should always be considered in the differential
      diagnosis of any spreading cellulitis in the right lumbar area or right lower
      abdominal quadrant in the presence of limited urinary symptoms and little or no
      abdominal signs.

PMID- 14584765
TI  - Splenic anisakiasis resulting from a gastric perforation: an unusual occurrence.
AB  - We report a case of gastric perforation by Anisakis sp. with consequent
      localization of the larva in the spleen. An 86-year-old white woman was admitted
      to our surgical department with a diagnosis of acute abdomen. She had a history
      of abdominal pain, and her laboratory data showed leukocytosis. In the plain
      abdominal radiograph, pneumoperitoneum was evident; a computed tomography (CT)
      scan of the abdomen confirmed the presence of extraluminal air. Anamnesis
      disclosed the ingestion of raw fish during the week preceding her illness. The
      patient was underwent emergency laparotomy. A small gastric perforation and a
      nodular area at the superior pole of the spleen were found. Surgical treatment
      was performed successfully and consisted of excision of the gastric lesion and
      splenectomy. The histological diagnosis revealed the presence of gastritis with
      an ulcer, and in the splenic tissue, some necrotic foci containing cross
      sectioned degenerated worms compatible with Anisakis larva.

PMID- 14584766
TI  - Enterolith ileus complicating afferent loop syndrome simulating acute
      pancreatitis.
AB  - Afferent loop syndrome after Billroth II gastrectomy is usually caused by those
      events that impair the evacuation of the afferent duodenal loop. The formation of
      an enterolith in an afferent loop is a rare but dangerous event. We present a
      unique report of a patient in whom a huge enterolith developed in the afferent
      loop of a Billroth II anastomosis, which led to intestinal occlusion. This
      migration occurred after a laparoscopic procedure, so we hypothesized that this
      procedure could be the cause of enterolith migration.

PMID- 14584767
TI  - Pseudomyxoma peritonei, origin from appendix: report of cases with images.
AB  - This report demonstrates the cases of a 47-year-old housewife, a 54-year-old
      female, and an 80-year-old woman in whom pseudomyxoma peritonei was found
      accidentally during surgery. Pseudomyxoma peritonei is a rare disease. No
      effective treatment is known. Modern treatments include radical surgical excision
      with appendicectomy and oophorectomy in women and adjuvant hyperthermic
      intraperitoneal and systemic chemotherapy. Major causes of morbidity and
      mortality are bowel obstruction and biliary obstruction. Five-year survival rate,
      depending on whether the disease is benign or malignant, is about 53-75%. Median
      survival is about 2 years under surgical management.

PMID- 14584768
TI  - Rectal carcinoma in Egyptian patients less than 40 years of age.
AB  - In Egypt, there is an increasing incidence of colorectal cancer, especially among
      patients < or = 40 years of age. The aim of this work was to study the
      characteristics of rectal cancer in a group of young Egyptian patients treated at
      Alexandria Main University hospital, Alexandria, Egypt, from June 1998 to June
      2001. This study included 50 rectal cancer patients. They were divided into two
      groups. Group I was patients < 40 years of age (26 patients), and group II was
      patients > 40 years of age (24 patients). Both groups were evaluated regarding
      history taking and physical examination, the gross tumor characteristics, the
      presence or absence of metastases, the histopathological characteristics of the
      tumor, and the treatment failure within the 3-year period of this study. Group I
      patients had a significantly longer duration of complaint. A total of 15.4% of
      patients in this group presented with intestinal obstruction compared with 8.3%
      in group II. A total of 30.8% of patients in group I presented with metastatic
      disease compared with 20.8% in group II. More patients in group I had fixed
      and/or circumferential lesions than did those of group II (38.5% and 53.8% versus
      20.8% and 8.3%, respectively). More patients in group I had nonresectable tumors.
      A total of 62.5% of group II patients underwent curative resection compared with
      53.8% of the patients in group I. A total of 38.5% of patients in group I had
      mucoid carcinoma compared with 8.3% in group II. At the end of the 3-year period
      of this study, only 38.5% of group I patients were alive and free of disease
      compared with 45.8% in group II. In Egypt, rectal cancer patients <40 years of
      age have more advanced disease at presentation and a higher incidence of
      treatment failure caused by both a delay in the diagnosis and a more aggressive
      pattern of the disease.

PMID- 14584769
TI  - Experience with hystidine tryptophan ketoglutarate versus University Wisconsin
      preservation solutions in transplantation.
AB  - We present our experience with histidine tryptophan ketoglutarate (HTK) and
      University Wisconsin (UW) preservation solutions in liver transplantation and a
      review of the literature in pancreas and kidney transplantation comparing these
      solutions. A group of 134 liver transplantations in 123 recipients was analyzed
      retrospectively. Grafts procured in adults were perfused with HTK in 63 cases and
      with UW in 71 cases. We compared results according to preoperative,
      intraoperative, and postoperative parameters, as well as complications and
      survival. No differences regarding donor and recipient data, intraoperative fresh
      frozen plasma (FFP) substitution, length of intensive care unit (ICU) stay, and
      ischemic damage of the graft were found. The rate of complications was comparable
      in both groups. However, the bilirubin was higher in the UW group. The rate of
      biliary complications was higher in the UW group (n = 8) versus the HTK group (n
      = 5). HTK ischemic type biliary lesions (ITBL) were only present in the UW group.
      Patient and graft survival were statistically nonsignificant. The data confirm
      that HTK and UW, with exception of biliary complications, are considered
      comparable in clinical liver transplantation. The same conclusion can be taken
      from the literature analyzed concerning renal transplantation, and in smaller
      groups of pancreas transplants, similar results were published.

PMID- 14584771
TI  - Supergastrinoma: simultaneous peptic ulceration of esophagus, stomach, and small
      intestine.
AB  - Synchronous involvement of the esophagus, stomach, and small intestine by peptic
      ulceration has not been previously described in the Zollinger-Ellison syndrome.
      Two patients presented with abdominal pain, diarrhea, weight loss, and dysphagia
      while on acid suppressants. Fasting hypergastrinemia was confirmed. Endoscopy
      revealed peptic stricture of the esophagus with ulcerations in the stomach,
      duodenum, and jejunum. Imaging showed a mass in the head of pancreas. The first
      patient underwent distal esophagectomy, total gastrectomy, and resection of the
      head of pancreas for a pancreatic primary. Resection of the third and fourth
      parts of the duodenum and proximal jejunum was undertaken in the second patient
      with a duodenal primary. Malignant gastrinoma was confirmed histologically.
      "Supergastrinoma" describes a tumor causing synchronous peptic ulceration and/or
      stricture extending from the esophagus to the jejunum. Operative management
      entails customized resection of the areas irretrievably damaged by the ulceration
      together with the tumor.

PMID- 14584770
TI  - Assessment of nosocomial urinary tract infections in orthopaedic patients: a
      prospective and comparative study using two different catheters.
AB  - Catheter-related nosocomial urinary tract infection in postoperative orthopedic
      and trauma patients was studied prospectively using nitrofuroxone-impregnated
      urinary catheters (study group) and regular silicone-coated Foley catheters.
      Fifty adults in each group were randomly assigned. In Group A, antibiotic
      impregnated catheters were used, and in the other, non-antibiotic-impregnated
      urinary catheters were used (Group B). The variables studied were age, sex, type
      of surgery, duration of surgery, number of catheter days, days of intravenous
      line, and hospital days. In patients, urinary tract infection (UTI) was diagnosed
      by culture and the organism was isolated. The average age in the study group was
      43.90 years (range, 14-95 years) compared with the control group (mean age, 42.22
      years; range, 14-102 years). Catheter days in the nitrofuroxone-impregnated
      catheters was 7.9 days (range, 2-37 days) versus 7.2 days (range, 2-30 days). The
      intravenous line in the group was 9.16 days (range, 2-35 days) versus 8.8 days (2
      22 days). There were six infections (P = 0.028) in the control group compared
      with the study group. The length of operation was similar in each group. Our
      study indicates that nitrofuroxone-impregnated catheters have the potential to
      reduce nosocomial catheter-related UTIs in postoperative orthopedic and trauma
      patients.

PMID- 14584772
TI  - Management of common bile duct stones: the state of the art in 2000.
AB  - Biliary lithiasis is a widespread disease all over the world; one-third of the
      white population presents with stones in the biliary ducts. In Chile, it is
      present in 47% of adult females. The most common complications of this pathology
      are acute cholecystitis, choledocholithiasis, acute pancreatitis, retained common
      bile duct (CBD) stones, and gallbladder cancer; these constitute a serious health
      problem in Chile. The aim of this study was to update the information related to
      choledocholithiasis after 10 years of laparoscopic biliary surgery. To achieve
      this objective, we retrospectively analyzed the last 100 cases of
      choledocholithiasis admitted to the University of Chile Clinical Hospital in
      2000. Prevalence by sex and age was determined. Clinical diagnosis was
      demonstrated to be effective in 92.3% of the cases; laboratory tests and
      ultrasound were effective in 81% and 90% of the cases, respectively. Diagnosis of
      cholelithiasis and choledocholithiasis as one unique entity corresponded to 53%
      of the sample; 47% of the remaining choledocholithiasis cases corresponded to
      retained CBD stones in patients previously cholecystectomized. Time of appearance
      of symptoms of this residual pathology was reviewed. All methods or procedures
      employed to treat this pathology were studied, and it was found that endoscopic
      cholangiography (ERCP) was the most frequently used procedure. Also, results of
      other alternative procedures, such as open surgery or ERCP combined with
      laparoscopic cholecystectomy, were considered. Finally, this study was
      complemented with a thorough bibliographic review of more than 100 publications
      on the subject that were published in high-impact surgical reviews, emphasizing
      the course of treatment followed during the last 7 years.

PMID- 14584773
TI  - Surgical treatment for giant solid tumors of the mediastinum: a study of 26
      cases.
AB  - Twenty-six patients with giant solid tumors of the mediastinum (GSTM) were
      treated surgically from 1975 to 2000. Femorofemoral cardiopulmonary bypass (CPB)
      was used before induction of anesthesia as a precaution against total tracheal
      occlusion in two cases. Resection of the tumor was accomplished in all patients,
      combined with partial pericardium resection in five cases, left upper lobe of
      lung resection in two cases, and reconstruction of the superior vena cava (SVC)
      and innominate vein in four cases. The weights of resected tumors ranged from 1.1
      to 4.8 kg, with an average of 2.2 kg. The majority were benign (22 of 26, 84.6%).
      The postoperative complications included two cases with recurrent laryngeal nerve
      injury, three cases with wound infection, and two cases with dilatant
      pneumonedema. Diagnosis of GSTM was not difficult based on imaging and needle
      biopsy. Femorofemoral CPB is recommended before induction of anesthesia for
      patients with superior airway obstruction and superior vena cava occlusion.
      Perioperative management includes strict hemostasis, proper chest wall
      reconstruction, and prevention of re-expansion pulmonary edema.

PMID- 14584774
TI  - Surgical treatment for elderly breast cancer patients over the age of 70.
AB  - Because elderly breast cancer patients differ in various biological
      characteristics from younger patients, it is important to clarify the clinical
      characteristics and treatment results of elderly patients with this disease. A
      total of 332 breast cancer cases (327 patients) who received surgery were divided
      into three groups, consisting of a premenopause group younger than 50 years of
      age (group A, N = 144), a postmenopause group younger than 70 years of age (group
      B, N = 140), and elderly cases 70 years of age or older (group C, N = 48). A
      positive node involvement was seen in about 40% of all cases, but the lymph node
      positivity of group C was significantly lower than that of group A or B. The
      postoperative 5-year survival rates of groups A, B, and C were 88.9%, 87.5%, and
      89.4% at all stages, and 90.2%, 86.2%, and 91.4% at stages I and II,
      respectively. Only in group C did survival rates show no significant difference
      between node status. We conclude that both radical and cosmetic surgical
      treatments performed in elderly breast cancer patients aged 70 years or older are
      as effective as in younger breast cancer patients.

PMID- 14584775
TI  - A 10-year experience of unsuspected gallbladder cancer after laparoscopic
      cholecystectomy.
AB  - Unsuspected gallbladder cancer after laparoscopic cholecystectomy (LC) is a
      cancer that was previously manipulated by laparoscopic technique. The reported
      incidence was 0.3-1% and became an emerging problem as the popularity of LC
      increased. Lack of reliable data could address the outcome of reresection or
      nonreresection patients and the standard management. This study reviewed a single
      center experience in managing unsuspected gallbladder cancer patients after LC
      between July 1, 1992 and July 1, 2000 who had at least 2 years of follow-up.
      There were 11 patients (0.6%) postoperatively diagnosed with gallbladder cancer
      after 1825 LCs. Group A included three patients (28%) with nontransmural
      invasion, group B included four patients (36%) who had transmural invasion
      without secondary surgical intervention, and group C included four patients (36%)
      with reresection. The perioperation parameters and strategies were collected and
      compared. A review of the literature was performed simultaneously, and we
      concluded that unsuspected gallbladder cancer with nontransmural invasion needs
      no further treatment; however, aggressive reresection is beneficial to transmural
      invasion cancer, and prevention of bile spillage during LC should be the goal of
      every surgeon.

PMID- 14584776
TI  - The Drosophila pleiohomeotic mutation enhances the Polycomblike and Polycomb
      mutant phenotypes during embryogenesis and in the adult.
AB  - In Drosophila, the spatially restricted expression of the homeotic genes is
      controlled by Polycomb group (PcG) repression. PcG proteins appear to form
      different complexes to repress this gene expression. Although the pleiohomeotic
      gene (pho) shares mutational phenotypes with other PcG mutations, which
      demonstrates that PHO binds directly with a Polycomb (Pc)-containing complex, the
      genetic interactions of pho with other PcG genes have not been examined in
      detail. Here we investigated whether pho interacts with Polycomblike (Pcl) and
      Polycomb (Pc) during embryonic and adult development using developmental and
      genetic approaches. Pcl and Pc strongly enhanced pho phenotypes in the legs and
      tergite of the adult fly. Embryonic cuticle transformation was also greatly
      enhanced in Pcl; pho or Pc; pho double mutant embryos. The double mutant
      phenotypes were more severely affected by the pho maternal effect mutation than
      in zygotic mutant background, suggesting dosage-dependent processes. Taken
      together, these results provide genetic evidence of an interaction between PHO
      with other Polycomb group proteins at the embryonic and adult stages, and of the
      functioning of PHO as a component of the PcG complex.

PMID- 14584777
TI  - XMam1, the Xenopus homologue of mastermind, is essential to primary neurogenesis
      in Xenopus laevis embryos.
AB  - Notch signaling is involved in cell fate determination and is evolutionally
      highly conserved in vertebrates and invertebrates. Mastermind is a nuclear
      protein which participates in Notch signaling and is involved in direct
      transactivation of target genes. Here we analyzed the expression and the function
      of Xenopus mastermind1 (XMam1) in the process of primary neurogenesis. XMam1 is
      3,425 bp and encodes 1,139 amino acids. Overall, Mastermind proteins consist of a
      basic domain, two acidic domains and a glutamine-rich domain, which are highly
      conserved among species. The ubiquitous expression of XMam1 was observed in both
      maternal and zygotic stages. Whole-mount in situ hybridization showed that XMam1
      mRNA was present in the ectoderm by the gastrula stage and localized at the
      anterior neural region in the neurula stage. Thereafter, XMam1 expression was
      restricted to the eye and otic vesicle in the tailbud-stage embryo. XMaml
      overexpression caused the repression of primary neural formation. The truncated
      form of XMam1 (lacking the C-terminus of XMam1; XMam1deltaC) led to excess
      formation of primary neurons. Furthermore, XMam1deltaC strongly repressed XESR-1
      transactivation. These results show that XMaml is involved in primary
      neurogenesis by way of Notch signaling and is an essential component for
      transactivation of XESR-1 in Xenopus laevis embryos.

PMID- 14584778
TI  - Amphibian in vitro heart induction: a simple and reliable model for the study of
      vertebrate cardiac development.
AB  - Amphibian embryos are an excellent model system for analyzing the mechanisms of
      vertebrate cardiogenesis. Studies of heart development in Xenopus have, for
      example, revealed that the inductive interaction of the heart primordia with the
      adjacent underlying endoderm and dorsal lip starts at the early stages of
      gastrulation. However, the molecular basis of those early inductive events and
      the genes expressed during the early phases of heart differentiation remain
      largely unknown. Amphibian blastula embryos contain pluripotent cells in their
      ectodermal region, called the "animal cap," which fortunately can be exploited
      for understanding a variety of organogenesis processes. Despite an enormous
      potential for analysis, the use of this system in cardiogenesis research has
      languished due to a lack of information concerning appropriate culture methods.
      Herein we report conditions for generating an in vitro heart induction system and
      present evidence from two types of in vivo transplantations, that the cultured
      heart rudiment can develop and function in the adult organism. It is expected
      that the fundamental principles established in this model system will provide a
      versatile research platform for a variety of organ engineering projects,
      including modifying in vitro organ growth with exogenous components (e.g. various
      growth factors) and developing methods for preparing tissue for transplantation.

PMID- 14584779
TI  - Ca2+ released via IP3 receptors is required for furrow deepening during
      cytokinesis in zebrafish embryos.
AB  - We have previously visualized three Ca2+ transients, generated by release from
      intracellular stores, which are associated with cytokinesis during the early cell
      division cycles of zebrafish embryos: the furrow positioning, propagation and
      deepening transients. Here we demonstrate the requirement of the latter for
      furrow deepening, and identify the Ca2+ release channels responsible for
      generating the deepening transient. The introduction of the Ca2+ buffer 5,5'
      dibromo-BAPTA, at an appropriate time to challenge only the deepening transient,
      resulted in the dissipation of this transient and an inhibition of furrow
      deepening. Introduction of antagonists of the inositol 1,4,5-trisphosphate (IP3)
      receptor (heparin and 2-aminoethoxydiphenylborate; 2-APB) at the appropriate
      time, blocked the furrow deepening transient and resulted in an inhibition of
      furrow deepening. In contrast, antagonists of the ryanodine receptor and the
      NAADP-sensitive channel had no effect on either the furrow deepening transient or
      on furrow deepening. In addition, microinjection of IP3 led to the release of
      calcium from IP3-sensitive stores, whereas the introduction of caffeine or cADPR
      failed to induce any increase in intracellular Ca2+. Our new data thus support
      the idea that Ca2+ released via IP3 receptors is essential for generating the
      furrow deepening transient and demonstrate a requirement for a localized
      cytosolic Ca2+ riseforthe furrow deepening process. We also present data to show
      that the endoplasmic reticulum and IP3 receptors are localized on either side of
      the cleavage furrow, thus providing the intracellular Ca2+ store and release
      mechanism for generating the deepening transient.

PMID- 14584780
TI  - Allogeneic interactions in Hydractinia: is the transitory chimera beneficial?
AB  - The colonial marine hydroid, Hydractinia, exhibits four possible outcomes to
      allogeneic contacts: passive rejection, aggressive rejection, stable fusion and
      transitory fusion. In the special case of transitory fusion, Hydractinia colonies
      undergo tissue fusion, followed by tissue death at the original contact area, and
      colony separation. This type of rejection is different in several aspects from
      the rejection process that accompanies incompatible encounters. It has been
      suggested that in transitory fusion, the colonies gain immediate benefits from
      fusion, mainly due to size increase, without succumbing to costs associated with
      fusion (germ line parasitism). We report a long-term observation of repeated
      fusion and separation cycles in clones featuring transitory fusion that revealed
      a slow-down of specific growth rates following fusion, and recovery in growth
      rates following separation. Very rapid transfer of stained material between
      partners in transitory chimeras provides suggestive evidence that protection
      against germ line parasitism is far from being guaranteed by separation. Our data
      cast doubt as to whether the benefits considered for transitory fusion are
      sustainable and support the already made suggestion that fusion with self, rather
      than fusion with kin, has been the major selective force governing the evolution
      of allorecognition in colonial invertebrates.

PMID- 14584781
TI  - The role of alpha-amidated neuropeptides in hydroid development--LWamides and
      metamorphosis in Hydractinia echinata.
AB  - Peptides are increasingly attracting attention as primary signals in the control
      of development. Even though a large number of peptides have been characterized in
      cnidarians, little experimental evidence addresses their endogenous role. The
      life cycle of Hydractinia echinata includes metamorphosis from planula larva into
      the adult stage of the polyp. This process of stage conversion includes internal
      signalling, which controls cell cycle activity, cell differentiation, cell death
      and proportion-controlled morphogenesis. LWamide peptides are considered to be
      part of the control system. We implemented methods to silence gene activity by
      dsRNAi in Hydractinia and show a substantial knock-down of LWamide gene activity.
      In addition, LWamide function was knocked-out pharmacologically by targeting the
      biosynthesis of amidated peptides and thus preventing functional LWamides. Here
      we show that extinction of bioactive LWamides from planulae causes loss of
      metamorphosis competence, a deficiency which can be rescued by synthetic LWamide
      peptides. Thus, it is shown that LWamides are indispensable and act by conveying
      outer metamorphosis stimuli to target cells within the animal. Considering non
      availability of genetic analysis and the so-far limited success in expressing
      transgenes in hydroids, gene functions are difficult to analyse in hydroids. The
      approach as outlined here is suitable for functional analysis of genes encoding
      amidated peptides in hydroids.

PMID- 14584783
TI  - Sox9, a novel pancreatic marker in Xenopus.
AB  - The pancreas is a mixed exocrine and endocrine gland involved in the control of
      many homeostatic functions. During embryogenesis, the pancreas arises from dorsal
      and ventral evaginations of the foregut that will subsequently fuse into a single
      organ. The characterization of early genes expressed in the developing pancreas
      is critical to understand its specification and differentiation. Here we report
      the expression pattern of Sox9, a member of the Sox family of transcription
      factors, during development of the Xenopus pancreas and compare its expression to
      that of a well characterized pancreatic marker, Pdx1. By whole-mount in situ
      hybridization, Sox9 was first detected at stage 25 in the pancreatic anlagen-
      dorsally in the prospective foregut and ventrally on each side of the liver
      diverticulum. As development proceeds, Sox9 expression can be used to trace the
      development of the dorsal and ventral pancreatic buds and their repositioning
      associated with the dynamic movements of the gastrointestinal tract. Sox9
      expression in the pancreatic rudiment was identical to that of Pdx1. However,
      while Pdx1 is expressed in both the pancreatic buds and the duodenum, Sox9 was
      restricted to ventral and dorsal pancreatic buds. Sox9 and Pdx1 are thus two of
      the earliest genes expressed in the presumptive pancreatic tissue.

PMID- 14584782
TI  - Abnormal sex-duct development in female moles: the role of anti-Mullerian hormone
      and testosterone.
AB  - We have performed a morphological, hormonal and molecular study of the
      development of the sex ducts in the mole Talpa occidentalis. Females develop
      bilateral ovotestes with a functional ovarian portion and disgenic testicular
      tissue. The Mullerian ducts develop normally in females and their regression is
      very fast in males, suggesting a powerful action of the anti-Mullerian hormone in
      the mole. RT-PCR demonstrated that the gene governing this hormone begins to be
      expressed in males coinciding with testis differentiation, and expression
      continues until shortly after birth. Immunohistochemical studies showed that
      expression occurs in the Sertoli cells of testes. No expression was detected in
      females. Wolffian duct development was normal in males and degenerate in prenatal
      females, but developmental recovery after birth gave rise to the formation of
      rudimentary epididymides. This event coincides in time with increasing serum
      testosterone levels and Leydig cell differentiation in the female gonad, thus
      suggesting that testosterone produced by the ovotestes is responsible for
      masculinisation of female moles. During postnatal development, serum testosterone
      concentrations decreased in males but increased in females, thus approaching the
      levels that adult males and females have during the non-breeding season.

PMID- 14584784
TI  - Chemical approaches to studying transcription.
AB  - Gene transcription is one of the most important and complex processes in biology
      but great advances are being made into understanding its molecular mechanisms.
      Selective modulators of nuclear receptors that can regulate transcription of
      specific genes allow for the comparative analysis of different states of
      transcription. Techniques to monitor the binding of proteins to DNA leading up to
      transcription have also increased our knowledge of the events involved in the
      initiation of transcription. While still in its infancy, the use of chemical
      tools to study transcription shows great promise in dissecting a complex
      molecular process.

PMID- 14584785
TI  - Rigid optically-active D2 and D3 macrocycles.
AB  - The synthesis and characterization of novel optically-active macrocycles,
      obtained by esterification reaction from a binaphthyl-containing diol and
      phthalic or terephthalic acids, and possessing overall D2 or D3 symmetry, is
      described.

PMID- 14584787
TI  - A highly selective and sensitive fluorescent PET (photoinduced electron transfer)
      chemosensor for Zn(II).
AB  - The naphthalimide derivative 1 was designed as a fluorescence PET sensor for
      Zn(II); 1 showed excellent selectivity for Zn(II) at pH 7.4, even in the presence
      of other competitive cations, the emission, being pH independent above pH 3.5,
      was switched on upon Zn(II) recognition.

PMID- 14584786
TI  - Synthesis of (-)-gloeosporone, a fungal autoinhibitor of spore germination using
      a pi-allyltricarbonyliron lactone complex as a templating architecture for 1,7
      diol construction.
AB  - The synthesis of the germination self-inhibitor (-)-Gloeosporone is reported. The
      embedded 1,7-diol motif in the product is constructed by an ironcarbonyl tether
      controlled Mukaiyama aldol reaction. The key step in the synthesis is the
      reductive removal of the ligating iron species by treatment of an acetoxycomplex
      6 with lithium naphthalenide.

PMID- 14584788
TI  - Binding affinity and inhibitory potency of neomycin and streptomycin on the Tat
      peptide interaction with HIV-1 TAR RNA detected by on-line acoustic wave sensor.
AB  - The binding of two aminoglycoside antibiotics, neomycin and streptomycin, to a
      segment of the transactivation responsive region (TAR) RNA of the human
      immunodeficiency virus, and their inhibitory potency to disrupt the interaction
      of the RNA with a regulatory Tat protein-derived peptide, have been studied using
      a flow-through acoustic wave detector system. Binding affinity is directly
      correlated with the inhibitory potency of these molecules and the acoustic wave
      detection system shows that neomycin exhibits at least a ten-fold greater
      affinity for TAR RNA and that it is also a more potent inhibitor than
      streptomycin. These results are in agreement with previous studies. However,
      unlike the time-consuming batch-based assays, use of the flow-through format
      offers considerable potential for the rapid screening of the chemistry of
      relatively small-molecule-nucleic acid binding events.

PMID- 14584790
TI  - Synthesis of arylboronates by the palladium catalysed cross-coupling reaction in
      ionic liquids.
AB  - The palladium catalysed cross-coupling reaction of aryl iodides and bromides with
      pinacolborane in 1,3-dialkylimidazolium tetrafluoroborates and
      hexafluorophosphates producing arylboronates is described.

PMID- 14584789
TI  - Enzymic synthesis of 3-[3- 13C]dehydroquinic acid.
AB  - The title compound has been prepared enzymically over four steps from
      commercially available D-[5- 13C]fructose.

PMID- 14584791
TI  - Design, synthesis, conformational analysis and nucleic acid hybridisation
      properties of thymidyl pyrrolidine-amide oligonucleotide mimics (POM).
AB  - Pyrrolidine-amide oligonucleotide mimics (POM) 1 were designed to be
      stereochemically and conformationally similar to natural nucleic acids, but with
      an oppositely charged, cationic backbone. Molecular modelling reveals that the
      lowest energy conformation of a thymidyl-POM monomer is similar to the
      conformation adopted by ribonucleosides. An efficient solution phase synthesis of
      the thymidyl POM oligomers has been developed, using both N-alkylation and
      acylation coupling strategies. 1H NMR spectroscopy confirmed that the highly
      water soluble thymidyl-dimer, T2-POM, preferentially adopts both a configuration
      about the pyrrolidine N-atom and an overall conformation in D2O that are very
      similar to a typical C3'-endo nucleotide in RNA. In addition the nucleic acid
      hybridisation properties of a thymidyl-pentamer, T5-POM, with an N-terminal
      phthalimide group were evaluated using both UV spectroscopy and surface plasmon
      resonance (SPR). It was found that T5-POM exhibits very high affinity for
      complementary ssDNA and RNA, similar to that of a T5-PNA oligomer. SPR
      experiments also showed that T5-POM binds with high sequence fidelity to ssDNA
      under near physiological conditions. In addition, it was found possible to
      attenuate the binding affinity of T5-POM to ssDNA and RNA by varying both the
      ionic strength and pH. However, the most striking feature exhibited by T5-POM is
      an unprecedented kinetic binding selectivity for ssRNA over DNA.

PMID- 14584792
TI  - Acyclic, achiral enamide nucleoside analogues. The importance of the C=C bond in
      the analogue for its ability to mimic natural nucleosides.
AB  - The conformations of an acyclic, achiral enamide thymidine analogue 1 have been
      studied by model building and geometry calculations, as well as by NMR NOE and UV
      experiments. The results indicate that there are no significant barriers to
      rotation around any of the sigma bonds, in particular the N1-C1' enamide bond,
      and that the analogue should be able to accommodate conformations that mimic the
      conformations of natural nucleosides in A- and B-type helices quite well. For
      comparison the saturated analogue 2 has been prepared and built into
      oligonucleotides. It is shown that incorporation of 2 in oligonucleotides results
      in a much larger depression of the melting temperature (deltaTm -10 to -12.5
      degrees C) than does incorporation of 1 (deltaTm -5 to -6.5 degrees C).

PMID- 14584793
TI  - Cyclic phosphopeptides for interference with Grb2 SH2 domain signal transduction
      prepared by ring-closing metathesis and phosphorylation.
AB  - Cyclic phosphopeptides were prepared using ring-closing metathesis followed by
      phosphorylation. These cyclic phosphopeptides were designed to interact with the
      SH2 domain of Grb2, which is a signal transduction protein of importance as a
      target for antiproliferative drug development. Binding of these peptides to the
      Grb2 SH2 domain was evaluated by a surface plasmon resonance assay. High affinity
      binding to the Grb2 SH2 domain was maintained upon macrocyclization, thus
      indicating that this method can be used to assemble high affinity cyclic
      phosphopeptides that interfere with signal transduction cascades.

PMID- 14584794
TI  - Biomimetic studies on the mechanism of stereoselective lanthionine formation.
AB  - Selenocysteine derivatives are useful precursors for the synthesis of peptide
      conjugates and selenopeptides. Several diastereomers of Fmoc-3-methyl-Se
      phenylselenocysteine (FmocMeSec(Ph)) were prepared and used in solid phase
      peptide synthesis (SPPS). Once incorporated into peptides, the phenylselenide
      functionality provides a useful handle for the site and stereospecific
      introduction of E- or Z-dehydrobutyrine residues into peptide chains via
      oxidative elimination. The oxidation conditions are mild, can be performed on a
      solid support, and tolerate functionalities commonly found in peptides, including
      variously protected cysteine residues. Dehydropeptides containing unprotected
      cysteine residues undergo intramolecular stereoselective conjugate addition to
      afford cyclic lanthionines and methyllanthionines, which have the same
      stereochemistry as found in lantibiotics, a family of ribosomally synthesized and
      post-translationally modified peptide antibiotics. The observed stereoselectivity
      is shown to originate from a kinetic rather than a thermodynamic preference.

PMID- 14584795
TI  - Synthesis of the TT pyrimidine (6-4) pyrimidone photoproduct-thio analogue
      phosphoramidite building block.
AB  - The phosphoramidite building block synthesis of the thio analogue at the 5,6
      dihydropyrimidine C5 position of the thymidylyl(3'-5')thymidine (6-4)
      photoproduct 1 is presented. This compound was readily obtained from the
      appropriately protected dinucleotide P-methyl-5'-O-dimethoxytritylthymidilyl(3' -
      > 5')-4-thiothymidine 2 after irradiation at 366 nm, then S-sulfenylmethylation
      of the thiol function of the resulting (6-4) adduct, and phosphitylation of the
      3'-hydroxyl group.

PMID- 14584796
TI  - A new access to polyhydroxy piperidines of the azasugar class: synthesis and
      glycosidase inhibition studies.
AB  - A new synthetic strategy has been devised to access a variety of polyhydroxylated
      piperidines belonging to the azasugar class of glycosidase inhibitors. The key
      precursor (3aR, 7aR)-5-benzyl-2,2-dimethyl-7-methylenehexahydro[1,3]dioxo[4,5
      c]pyridine is obtained by photoinduced electron transfer (PET) cyclization of the
      corresponding alpha-trimethylsilylmethylamine radical cation to the tethered
      acetylene functionality. The new molecules have been evaluated for inhibitory
      properties for certain beta-glycosidases and have been found to be moderate to
      weak inhibitors of the enzymes under study.

PMID- 14584797
TI  - Design, synthesis and in vitro cytotoxicity studies of novel pyrrolo [2,1][1,4]
      benzodiazepine-glycosylated pyrrole and imidazole polyamide conjugates.
AB  - The design, synthesis and biological evaluation of novel pyrrolo [2,1][1,4]
      benzodiazepine-water insoluble 31-38 and water soluble 39-46 glycosylated pyrrole
      and imidazole polyamide conjugates are described that involved mercuric chloride
      mediated cyclization of the corresponding amino diethyl thioacetals. The
      compounds were prepared with varying numbers of pyrrole and imidazole containing
      polyamides and incorporating glucose moieties in order to improve the water
      solubility of PBD-polyamide conjugates and probe the structural requirements for
      optimal in vitro antitumor activity. These compounds were tested against a panel
      of 60 human cancer cells by the National Cancer Institute, and demonstrated that
      the water soluble PBD-polyamide compounds exhibited a higher level of cytotoxic
      activity than the existing natural and synthetic pyrrolo [2,1-c][1,4]
      benzodiazepines. The cytotoxic activities of these compounds dramatically
      increase after hydrolysis of their acetylated counterparts. The activity data
      summarized in Table 1 and Table 2 show that the solubility of the PBD-polyamides
      and also the type of heterocycle play important roles influencing the cytotoxic
      activity of the PBD-polyamide conjugates. The PBD-glycosylated polyamide (water
      soluble) conjugates 39-46 are highly cytotoxic against many human cancer cell
      lines in comparison with the PBD-polyamide (water insoluble version) conjugates.

PMID- 14584798
TI  - A new paclitaxel prodrug for use in ADEPT strategy.
AB  - A new paclitaxel prodrug intended for use in Antibody-Directed Prodrug Therapy
      (ADEPT) or Prodrug Monotherapy (PMT) has been prepared. This prodrug was
      originally designed to be activated into the drug by human beta-glucuronidase. In
      order to enhance the liberation rate of paclitaxel, an elongated spacer system
      including a nitro-aromatic derivative and a N,N'-methylethylenediamine was
      incorporated between the sugar moiety and the drug. Indeed, this new prodrug
      proved to be activated significantly faster than a former paclitaxel prodrug
      containing a conventional spacer.

PMID- 14584799
TI  - Synthesis, molecular modeling and biological activity of methyl and thiomethyl
      substituted pyrimidines as corticotropin releasing hormone type 1 antagonists.
AB  - Four small, targeted libraries of differentially substituted amino pyrimidines
      were synthesized in moderate to good yields. Excellent regiochemistry was
      observed for substitution at C2/C4 with selectivity > 50:1 noted. All analogues
      were screened for their ability to interact with CRH1 and CRH2 receptors. In all
      instances only poor agonistic and/or antagonistic behaviour was noted at CRH2.
      However, several compounds were potent and selective CRH1 antagonists, most
      notably 13a Ki = 39 nM. Additionally we have utilized these data and that
      recently reported by others to refine our original CRH1 pharmacophore (J Med.
      Chem., 1999, 42, 2351-2357).

PMID- 14584800
TI  - Chemistry and biology of khafrefungin. Large-scale synthesis, design, and
      structure-activity relationship of khafrefungin, an antifungal agent.
AB  - Large-scale synthesis, design, and structure-activity relationships of
      khafrefungin are reported. Khafrefungin is an antifungal agent that inhibits
      inositol phosphorylceramide (IPC) synthase, an enzyme involved in fungal
      sphingolipid biosynthesis. Unlike other inhibitors that inhibit the corresponding
      enzyme in fungi and mammals to the same extent, khafrefungin does not impair
      sphingolipid synthesis in mammals. We have developed an efficient method for
      large-scale synthesis of khafrefungin, and various khafrefungin derivatives were
      synthesized based on this method. While most of the khafrefungin derivatives lost
      antifungal activity, a lactone-type derivative had almost the same activity as
      khafrefungin. We also designed and synthesized derivatives which contain a five-
      or six-membered ring at the central part of the structure based on NOE
      experiments of khafrefungin. A macrocyclic khafrefungin derivative was also
      synthesized, but the antifungal activity was lost. These results suggest that the
      structure of khafrefungin might be strictly recognized in fungi.

PMID- 14584802
TI  - Competing sulfonylation and phosphonylation following rearrangement of an O
      sulfonyl-N-phosphinoylhydroxylamine with tert-butylamine: demonstration of a
      phosphonamidic-sulfonic anhydride intermediate and 18O-labelling evidence on how
      it may be formed.
AB  - Reaction of R(Ph)P(O)N HOSO2Bn (R = PhMeCH) with Bu(t)NH2 in CH2Cl2 gives a
      mixture of RP(O)(NHPh)-NHBu(t) and Bu(t)NHSO2Bn, the proportion of the
      sulfonamide increasing steadily (14.6% to 32.9%) as the concentration of amine is
      reduced (8.0 to 0.2 mol dm(-3)). Apparently the phenyl and sulfonate groups in
      the substrate become transposed, giving a phosphonamidic-sulfonic anhydride
      RP(O)(NHPh)OSO2Bn which then reacts at the phosphorus or sulfur atom to give the
      final products; an authentic sample of the anhydride gives similar mixtures of
      products. Substrate labelled with 18O in the sulfonyl position (57 mol% one 18O
      atom) gives sulfonamide containing most but not all of the label (43.7 mol% one
      18O atom with 2.0 mol dm(-3) amine). This implies partial equilibration of the
      three sulfonate oxygen atoms during rearrangement, or after the anhydride
      intermediate has been formed.

PMID- 14584803
TI  - Products from dehydration of dicarboxylic acids derived from anthranilic acid.
AB  - Treatment of N-(carboxymethyl)-anthranilic acids 1 with several dehydrating
      agents, gave the cyclic ortho amides 6, or the 7-membered anhydrides 7. After
      reaction of N-(carboxymethyl)-anthranilic acid (1a) with acetic anhydride, a
      diacetylated fused diketopiperazine indole dimer (18) could be isolated.
      Dehydrations of 2,2'-iminobis-benzoic acid led to the corresponding cyclic ortho
      amides 23. The dynamic behaviour of some of these compounds, and their
      precursors, was studied.

PMID- 14584801
TI  - Antitumour polycyclic acridines. Palladium(0) mediated syntheses of quino[4,3,2
      kl]acridines bearing peripheral substituents as potential telomere maintenance
      inhibitors.
AB  - Pd(0) mediated couplings between substituted 2-(pivaloylamino)benzeneboronic
      acids and 3,6-disubstituted-10-methylacridones 13 bearing a bromo or
      trifluoromethylsulfonyloxy substituent in the 1-position yield intermediate 1
      arylacridones 16 which can be can be cyclised to new 8-methylquino[4,3,2
      kl]acridines 17 with phosphorus oxychloride or 6 M HCI in EtOH. Heck reactions
      between triflate-substituted substrates 17 and acrylic acid derivatives afforded
      quinoacridines with unsaturated side-chains in the 6-position. Alkylboranes,
      prepared by interaction of 9-borabicyclo[3,3,1]nonane (9-BBN) and allyl acetate
      or N-allyltrifluoroacetamide, participated in Suzuki-Miyaura reactions with
      chloro-substituted 8-methylquinoacridines to form derivatives bearing
      functionalised propyl groups in the 6- and 10-positions. Representative 8
      methylquinoacridines were methylated with methyl iodide to yield telomerase
      inhibitory 8,13-dimethylquinoacridinium iodides 24.

PMID- 14584804
TI  - Macrocyclic amines as catalysts of the hydrolysis of the triphosphate bridge of
      the mRNA 5'-cap structure.
AB  - The reactions of a 5'-cap model compound P1-(7-methylguanosine) P3-guanosine
      5',5'-triphosphate, m7GpppG, were studied in the presence of three different
      macrocyclic amines (2-4) under neutral conditions. The only products observed in
      the absence of the macrocycles resulted from the base-catalysed imidazole ring
      opening and the acid-catalysed cleavage of the N7-methylguanosine base, whereas
      in the presence of these catalysts hydrolysis of the triphosphate bridge
      predominated. The latter reaction yielded guanosine 5'-monophosphate, guanosine
      5'-diphosphate, 7-methylguanosine 5'-monophosphate and 7-methylguanosine 5'
      diphosphate as the initial products, indicating that both of the phosphoric
      anhydride bonds were cleaved. The overall catalytic activity of all three
      macrocycles was comparable. The hydrolysis to guanosine 5'-diphosphate and 7
      methylguanosine 5'-monophosphate was slightly more favoured than the cleavage to
      yield guanosine 5'-monophosphate and 7-methylguanosine diphosphate. All the
      macrocycles also enhanced the subsequent hydrolysis of the nucleoside
      diphosphates, 2 being more efficient than 3 and 4.

PMID- 14584805
TI  - Aromaticity and antiaromaticity in fulvenes, ketocyclopolyenes, fulvenones, and
      diazocyclopolyenes.
AB  - The structures, energies, natural charges, and magnetic properties of 3-, 5-, 7-,
      and 9-membered cyclic polyenes 1-4, respectively, with exocyclic methylene, keto,
      ketenyl, and diazo substituents (a-d, respectively) were computed at the B3LYP/6
      311G+ **//B3LYP/6-311+G** level to elucidate their aromatic and antiaromatic
      properties. The corresponding conjugated cyclic cations le and 3e were also
      studied. The criteria used are isomerization energies (ISE), magnetic
      susceptibility exaltations (lambda), aromatic stabilization energies (ASE),
      nucleus independent chemical shifts (NICS), and bond length alternation (deltaR).
      Planar C2v structures were found to be the lowest energy minima with the
      exceptions of diazocyclopropene (1d), cycloheptafulvenone (3c),
      diazocycloheptatriene (3d), and all of the cyclononatetraene derivatives (4). The
      fulvenes (1a-4a) have modest aromatic or antiaromatic character, and are used as
      standards for comparison. By these criteria the ketenylidene and diazo
      cyclopropenes and cycloheptatrienes 1,3-c,d and oxo cyclopentadiene and
      cyclononatetraene 2,4b are antiaromatic, while the 5- and 9-ring ketenyl and
      diazo compounds and 3- and 7-ring ketones are aromatic. The degree of
      aromatic/antiaromatic character decreases with ring size. The consistent
      agreement with Huckel rule predictions for all the criteria shows their utility
      for the evaluation of the elusive properties of aromaticity and antiaromaticity.

PMID- 14584806
TI  - Model dialkyl peroxides of the fenton mechanistic probe 2-methyl-1-phenyl-2
      propyl hydroperoxide (MPPH): kinetic probes for dissociative electron transfer.
AB  - Two dialkyl peroxides, devised as kinetic probes for the heterogeneous electron
      transfer (ET), are studied using heterogeneous and homogeneous electrochemical
      techniques. The peroxides react by concerted dissociative ET reduction of the O-O
      bond. Under heterogeneous conditions, the only products isolated are the
      corresponding alcohols from a two-electron reduction as has been observed with
      other dialkyl peroxides studied to date. However, under homogeneous conditions, a
      generated alkoxyl radical undergoes a rapid beta-scission fragmentation in
      competition with the second ET resulting in formation of acetone and a benzyl
      radical. With knowledge of the rate constant for fragmentation and accounting for
      the diffuse double layer at the electrode interface, the heterogeneous ET rate
      constant to the alkoxyl radicals is estimated to be 1500 cm s(-1). The
      heterogeneous and homogeneous ET kinetics of the O-O bond cleavage have also been
      measured and examined as a function of the driving force for ET, deltaG(ET),
      using dissociative electron transfer theory. From both sets of kinetics, besides
      the evaluation of thermochemical parameters, it is demonstrated that the
      heterogeneous and homogeneous reduction of the O-O bond appears to be non
      adiabatic.

PMID- 14584807
TI  - Crystal structures and properties of mutagenic N-acyloxy-N-alkoxyamides--"most
      pyramidal" acyclic amides.
AB  - X-Ray data for two N-acyloxy-N-alkoxyamides, a class of direct-acting mutagens,
      indicate extreme pyramidalisation at the amide nitrogen in keeping with
      spectroscopic and theoretically determined properties of amides with
      bisoxosubstitution at nitrogen. The combined electronegativity of two oxygens
      leads to average angles at nitrogen of 107.8 and 108.1 degrees and [chiN] of 66
      degrees and 65 degrees. The sp3 nature of nitrogen results in negligible amide
      resonance as evidenced by long N-C(O) bonds, high IR carbonyl stretch
      frequencies, carbonyl 13C NMR data and very low amide isomerisation barriers. In
      addition, conformations in the solid state support a strong n(O)-sigma*(NOAc),
      anomeric interaction as predicted by molecular orbital theory. HF/6-31G*
      calculations on formamide, N-methoxyformamide and N-formyloxy-N-methoxyformamide
      support these findings.

PMID- 14584808
TI  - Sigma-adduct formation and oxidative substitution in the reactions of 4
      nitrobenzofurazan and some derivatives with hydroxide ions in water.
AB  - The reactions of hydroxide ions with 4-nitrobenzofurazan, 1a, 4
      nitrobenzofuroxan, 1b, and with three 4-nitro-7-substituted benzofurazans have
      been examined using 1H NMR and UV-visible spectroscopies. In each case initial
      reaction is at the 5-position to give an anionic sigma-adduct. Kinetic and
      equilibrium results are reported. NMR spectra show that in the case of 1a
      oxidation of the anionic adduct yields 4-nitro-5-hydroxybenzofurazan. In the case
      of 1b rearrangement of the 5-hydroxy adduct to the thermodynamically more stable
      7-hydroxy adduct, possibly by a Boulton-Katritzky mechanism, precedes oxidation.
      When the 7-substituent in the 4-nitrobenzofurazan is Cl, OMe or OPh the eventual
      product is 7-hydroxy-4-nitrobenzofurazan produced by nucleophilic displacement of
      the substituent.

PMID- 14584809
TI  - Circular dichroism spectra and absolute configuration of some aryl methyl
      sulfoxides.
AB  - The absorption and circular dichroism (CD) spectra of three aryl sulfoxides, i.e.
      (-)-(S)-1-naphthyl methyl sulfoxide, (S)-1, (-)-(S)-1-(2-methyl)naphthyl methyl
      sulfoxide, (S)-2 and (-)-(S)-9-phenanthryl methyl sulfoxide, (S)-3, have been
      interpreted by means of the coupled oscillator model formulated by DeVoe.
      Theoretical spectra have been calculated starting from input geometries provided
      by molecular mechanics (MMX) calculations and by employing standard spectroscopic
      parameters to describe the allowed transitions of the aromatic and the sulfoxide
      chromophores. The satisfactory agreement between the predicted and experimental
      spectra allows us to confirm the configurational assignment of these compounds as
      (-)/(S). The analysis of CD spectra, affording the right assignment of the
      absolute configuration (AC) of the alkyl aryl sulfoxides, then offers a practical
      alternative to the more complex vibrational circular dichroism spectroscopy and
      ab initio optical rotation calculation techniques that have been used very
      recently to assign the AC of (-)-2 and (-)-3.

PMID- 14584810
TI  - Neutral pi-associated porphyrin [2]catenanes.
AB  - A series of neutral porphyrin-containing catenanes has been synthesised,
      consisting of a zinc porphyrin strapped by a polyethylene glycol chain containing
      four or six ethylenoxy-units and incorporating a central naphthoquinol unit,
      interlinked with a naphthalene diimide macrocycle. The napthalene diimide
      precursor units exhibit only weak binding with the strapped porphyrins (Ka
      between 8 and 0.02 M(-1)), but good yields of the catenanes were obtained by
      Glaser coupling of the alkynyl napthalene diimide precursors in the presence of
      the porphyrins. Structures and solution conformations were determined by mass
      spectral and detailed 1H NMR studies. For the longer strapped porphyrins, the
      diimide macrocycle rotates around the central naphthoquinol unit at 420-450 times
      per second, while rotation is virtually prevented in the tighter strapped
      derivatives. A second dynamic process occurring in both sets of catenanes and
      described as 'yawing' leads to inequivalence in the naphthalene moieties. UV
      Visible spectra indicate charge transfer interactions and electronic
      communication between the two components of the catenane.

PMID- 14584811
TI  - Steroid-porphyrin conjugate for saccharide sensing in protic media.
AB  - A new saccharide receptor in protic media has been designed and synthesized. The
      receptor combines advantages of steroids, which are responsible for saccharide
      binding, and of the porphyrin moiety acting as a signalling component of the
      molecule due to changes in UV-vis electronic spectra. The synthesis is based on
      condensation of steroid aldehyde with pyrrole to form the porphyrin unit with
      four protected steroid moieties. After deprotection, meso-substituted porphyrin
      contains 12-hydroxy groups on the steroidal part. The receptor is soluble in
      aqueous solutions and exhibits high complexation affinity towards saccharides.
      Because the receptor extensively aggregates in water, most of the experiments
      were performed in 50% aqueous 2-propanol where aggregation is significantly
      eliminated. Binding is evidenced by spectral changes in the Soret region of the
      receptor in UV-vis absorption spectra allowing the evaluation of the binding
      constants. Additional confirmation of binding is obtained using 1H NMR, Raman and
      IR spectroscopies and the surface plasmon resonance technique. The receptor
      exhibits higher selectivity for oligosaccharides over monosaccharide. The results
      point to the importance of a combination of multiple binding via H-bonding and
      hydrophobic interactions.

PMID- 14584812
TI  - A new urea gelator: incorporation of intra- and intermolecular hydrogen bonding
      for stable 1D self-assembly.
AB  - A new bisurea gelator derived from 2,6-diaminopyridine has been developed. It
      efficiently gelates common organic and liquid crystalline (LC) solvents by
      forming elongated self-assembled fibres in solvents. X-Ray crystallography and 1H
      NMR measurements reveal that two urea groups in pyridine-based bisurea compounds
      form different hydrogen bonding patterns. One of two urea units is involved in
      intramolecular hydrogen bonding with the pyridyl nitrogen, while the other urea
      unit forms bifurcated intermolecular hydrogen bonding. This hydrogen-bonded
      structure is key for the fibrous self-assembly along with the efficient gelation.
      In addition, LC gels based on the pyridine-based gelator exhibit good
      electrooptic properties. These results indicate that the pyridine-based bisurea
      compound is a good gelator not only effective in gelation but also useful as a
      component of functional soft materials.

PMID- 14584813
TI  - Synapses everlasting: the passion of Carl Cotman.

PMID- 14584814
TI  - The successful aging of Carl Cotman: from proteins of the synapse, through
      sprouting, regeneration, and spinal cord injury to the mechanisms of brain aging.

PMID- 14584815
TI  - Glutamate, cell death, and hats off to Carl Cotman.

PMID- 14584816
TI  - Reactive synaptogenesis in aging and Alzheimer's disease: lessons learned in the
      Cotman laboratory.
AB  - Early experiments resulting in partial deafferentation of the rodent hippocampus
      demonstrated a robust reactive plasticity response that includes the replacement
      of lost synaptic contacts. Similar experiments carried out in the hippocampus of
      aged animals produced an alteration in the temporal sequence of the reactive
      plasticity response and a slowing of synaptic replacement. In Alzheimer's
      disease, one observes a marked reduction in the number of synaptic contacts in
      important association areas of the cortex and hippocampus. This reduction may be
      the result of an altered reactive plasticity response.

PMID- 14584817
TI  - Adventures in neural plasticity, aging, and neurodegenerative disorders aboard
      the CWC beagle.
AB  - This article recounts some of the scientific endeavors of Carl W. Cotman (CWC)
      during his journeys through the cellular circuitry of the mammalian brain. I have
      selected for consideration his findings that have been an important impetus for
      my own research; in several cases our different experiments have provided
      complementary data to support an hypothesis. Three examples are (i) Carl's
      studies of the roles of glutamate in synaptic transmission and plasticity in the
      adult brain and my studies of how glutamate regulates neurite outgrowth and cell
      survival in brain development; (ii) his and our studies of the mechanisms whereby
      amyloid beta-peptide damages and kills neurons; and (iii) Carl's evidence that
      physical activity regulates neurotrophin levels in the brain and our evidence
      that dietary restriction has similar effects and is neuroprotective. In case you
      have not yet realized how I chose a title for this article it is because Carl has
      a (very distant) connection with Charles Darwin-Darwin sailed on a vessel called
      the Beagle and Carl has studied beagle dogs, establishing them as a model for
      understanding the neurobiology of human brain aging.

PMID- 14584818
TI  - Patterning axonal guidance molecules using a novel strategy for microcontact
      printing.
AB  - We present here a two-step strategy for micropatterning proteins on a substrate
      to control neurite growth in culture. First, conventional microcontact printing
      is used to prepare a micropattern of protein A, which binds the Fc fragment of
      immunoglobulins. Then, a chimeric protein, consisting of the extracellular domain
      of a guidance protein recombinantly linked to the Fc fragment of IgG (prepared
      using conventional molecular techniques), is applied from solution. The chimeric
      protein binds to the patterned protein A, taking on its geometric pattern. Using
      this method, we have micropatterned the extracellular domain of the cell adhesion
      molecule, L1 (as an L1-Fc chimera) and demonstrated that it retains its ability
      to selectively guide axonal growth. L1-Fc micropatterned on a background of poly
      L-lysine resulted in selective growth of the axons on the micropattern, whereas
      the somata and dendrites were unresponsive. Substrates bearing simultaneous
      micropatterns of L1-Fc and poly-L-lysine on a background of untreated glass were
      also created. Using this approach, cell body position was controlled by
      manipulating the dimensions of the poly-L-lysine pattern, and the dendrites were
      constrained to the poly-L-lysine pattern, while the axons grew preferentially on
      L1-Fc. The two-step microcontact printing method allows preparation of substrates
      that contain guidance proteins in geometric patterns with resolution of
      approximately 1 microm. This method should be broadly applicable to many classes
      of proteins.

PMID- 14584819
TI  - The recurrent mossy fiber pathway of the epileptic brain.
AB  - The dentate gyrus is believed to play a key role in the pathogenesis of temporal
      lobe epilepsy. In normal brain the dentate granule cells serve as a high
      resistance gate or filter, inhibiting the propagation of seizures from the
      entorhinal cortex to the hippocampus. The filtering function of the dentate gyrus
      depends in part on the near absence of monosynaptic connections among granule
      cells. In humans with temporal lobe epilepsy and in animal models of temporal
      lobe epilepsy, dentate granule cells form an interconnected synaptic network
      associated with loss of hilar interneurons. This recurrent mossy fiber pathway
      mediates reverberating excitation that can reduce the threshold for granule cell
      synchronization. Factors that augment activity in this pathway include modest
      increases in [K+]o; loss of GABA inhibition; short-term, frequency-dependent
      facilitation (frequencies of 1-2 Hz); feedback activation of kainate
      autoreceptors; and release of zinc from recurrent mossy fiber boutons. Factors
      that diminish activity include short-term, frequency-dependent depression
      (frequencies < 1 Hz); feedback activation of type II metabotropic glutamate
      receptors; and the potential release of GABA, neuropeptide Y, adenosine, and
      dynorphin from recurrent mossy fiber boutons. The axon sprouting and reactive
      synaptogenesis that follow seizure-related brain damage can also create or
      strengthen recurrent excitation in other brain regions. These changes are
      expected to facilitate participation of these regions in seizures. Thus, reactive
      processes that are often considered important for recovery of function after most
      brain injuries probably contribute to neurological dysfunction in epilepsy.

PMID- 14584821
TI  - Cognitive experience and its effect on age-dependent cognitive decline in beagle
      dogs.
AB  - Test-sophisticated beagle dogs show marked age sensitivity in a size
      discrimination learning task, with old and senior dogs performing significantly
      more poorly than young dogs. By contrast, age differences in learning were not
      seen in dogs naive with respect to neuropsychological test experience. These
      results indicate that old animals benefit less from prior cognitive experience
      than young animals, which is an example of an age-dependent loss in plasticity.
      This finding also suggests that behaviorally experienced animals are a more
      useful model of human cognitive aging than behaviorally naive animals. We also
      looked at the effect of a program of behavioral enrichment in aged dogs. One year
      of enrichment did not lead to significant differences, but after 2 years the
      behaviorally enriched group performed significantly better than the control
      group. The effect after 2 years indicates that a prolonged program of cognitive
      enrichment can serve as an effective intervention in aged dogs. These findings
      demonstrate that cognitive abilities in aged animals can be modified by providing
      behavioral experience, indicating that cognitive abilities remain moderately
      plastic, even in very old animals.

PMID- 14584820
TI  - Central nervous system lesions that can and those that cannot be repaired with
      the help of olfactory bulb ensheathing cell transplants.
AB  - Growth-promoting macroglia (aldynoglia) with growth properties and immunological
      markers similar to Schwann cells, are found in loci of the mammalian CNS where
      axon regeneration occurs throughout life, like the olfactory sytem, hypothalamus
      hypophysis and the pineal gland. Contrary to Schwann cells, aldynoglia mingle
      freely with astrocytes and can migrate in brain and spinal cord. Transplantation
      of cultured and immunopurified olfactory ensheathing cells (OECs) in the spinal
      cord after multiple central rhizotomy, promoted sensory and central axon growth
      and partial functional restoration, judging by anatomical, electrophysiological
      and behavioural criteria. OEC transplants suppressed astrocyte reactivity, thus
      generally favouring axon growth after a lesion. However, the functional repair
      promoted by OEC transplants was partial in the best cases, depending on lesion
      type and location. Cyst formation after photochemical cord lesion was partially
      prevented but neither the corticospinal tract, interrupted by a mild contusion,
      nor the sectioned medial longitudinal fascicle, did regrow after OEC
      transplantation in the injured area.

PMID- 14584822
TI  - Neuritic alterations and neural system dysfunction in Alzheimer's disease and
      dementia with Lewy bodies.
AB  - Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) are
      neurodegenerative disorders that share progressive dementia as the common major
      clinical symptom. Damages to memory-related brain structures are the likely
      pathological correlate, and in both illnesses deposition of amyloidogenic
      proteins are present mainly within these limbic structures. Amyloid-beta-positive
      plaques and phospho-tau-positive neurofibrillary tangles are the main feature of
      AD and alpha-synuclein-positive Lewy bodies and Lewy neurites are found in DLB.
      Interestingly the associated proteins also interfere with synaptic function and
      synaptic plasticity. Here, we propose that the same neuronal circuits are
      disturbed within the hippocampal formation in AD and DLB and that in both
      diseases the associated proteins might lead to changes in synaptic plasticity and
      function. Thus both classic neuropathological changes and cellular dysfunctions
      might contribute to the cognitive impairments in AD and DLB.

PMID- 14584823
TI  - VEGF165 therapy exacerbates secondary damage following spinal cord injury.
AB  - Vascular endothelial growth factor (VEGF) demonstrates potent and well
      characterized effects on endothelial cytoprotection and angiogenesis. In an
      attempt to preserve spinal microvasculature and prolong the endogenous
      neovascular response observed transiently following experimental spinal cord
      injury (SCI), exogenous recombinant human VEGF (rhVEGF165) was injected into the
      injured rat spinal cord. Adult female Fischer 344 rats were subjected to moderate
      SCI (12.5 g-cm) using the NYU impactor. At 72 h after injury, animals were
      randomly assigned to three experimental groups receiving no microinjection or
      injection of saline or saline containing 2 microg of rhVEGF165. Acutely, VEGF
      injection resulted in significant microvascular permeability and infiltration of
      leukocytes into spinal cord parenchyma. 6 weeks postinjection, no significant
      differences were observed in most measures of microvascular architecture
      following VEGF treatment, but analysis of histopathology in spinal cord tissue
      revealed profound exacerbation of lesion volume. These results support the idea
      that intraparenchymal application of the proangiogenic factor VEGF may exacerbate
      SCI, likely through its effect on vessel permeability.

PMID- 14584824
TI  - Aging, amyloid, and Alzheimer's disease: a perspective in honor of Carl Cotman.
AB  - Deciphering the molecular basis of synaptic dysfuction in Alzheimer's disease
      (AD) has engaged the attention of scientists with diverse backgrounds and
      interests. The synthesis of experimental findings from neuropathology,
      biochemistry, genetics, animal modeling and even immunology, has provided a
      plausible model for the pathogenesis of the disorder. While not universally
      accepted, the so-called amyloid (or Abeta) hypothesis of AD is well supported
      scientifically and predicts several specific targets for therapeutic
      intervention. Some of these are now reaching the clinic, providing the final and
      most important test for this hypothetical mechanism of disease.

PMID- 14584826
TI  - Lysosomes and brain aging in mammals.
AB  - Hypotheses about the factors controlling the rate of brain aging are usually
      derived from 1) correlates of maximum life span across mammals or 2)
      investigations into the causes of age-related neuropathologies in humans. With
      regard to the former, the strong correlation between metabolic rate and longevity
      prompted a variety of free radical hypotheses of aging. There is also evidence
      that brain size affects life span independently of body metabolism rates. The
      second approach has led to a diverse array of pathogenic mechanisms and,
      importantly for the development of general hypotheses, the discovery of animal
      analogues. The present paper discusses the possibility that age-associated
      lysosomal dysfunction constitutes a generalized mammalian phenomenon that
      accounts for specific features of the aged human brain. Immunocytochemical
      studies using rats and dogs have identified lysosomal changes that begin early in
      adulthood and are most pronounced in brain areas known to be particularly
      vulnerable to age-related pathogenesis in humans. Experimentally induced
      lysosomal dysfunction in cultured brain slices from rats and mutant mice triggers
      a wide array of changes associated with the aged human brain, including
      meganeurites and intraneuronal tangles. Finally, there is evidence that at least
      some forms of proteolysis decrease with increasing brain size across the mammals.
      The above observations lead to the suggestion that the expansion of neuronal
      arborizations that occurred in conjunction with increases in brain size
      secondarily slowed both neuronal metabolism and protein turnover. These events
      could have served to reduce the rate at which lysosomes (and other organelles)
      fail.

PMID- 14584825
TI  - Plasticity and the spread of Alzheimer's disease-like changes.
AB  - Tangles are a major histopathological feature of Alzheimer's disease and their
      regional location and number correlate significantly with the individual's
      cognitive decline. Intriguingly, these tangles are formed only in a small subset
      of nerve cell types and are practically absent in most animal species examined so
      far. In humans, tangle formation seemingly starts decades before clinical signs
      of dementia are seen and spread over cortical areas in a regular manner described
      by the Braak classification. In the present article the role of plasticity
      related molecules and mechanisms are discussed considering their putative role in
      neuronal vulnerability and spread of tangles. Special emphasis is given to some
      aspects of lipid metabolism, that is, apolipoprotein E polymorphism, statin
      effects, and lysosomal dysfunction in Alzheimer's and Niemann-Pick C's diseases.

PMID- 14584827
TI  - Stress and plasticity in the limbic system.
AB  - The adult nervous system is not static, but instead can change, can be reshaped
      by experience. Such plasticity has been demonstrated from the most reductive to
      the most integrated levels, and understanding the bases of this plasticity is a
      major challenge. It is apparent that stress can alter plasticity in the nervous
      system, particularly in the limbic system. This paper reviews that subject,
      concentrating on: a) the ability of severe and/or prolonged stress to impair
      hippocampal-dependent explicit learning and the plasticity that underlies it; b)
      the ability of mild and transient stress to facilitate such plasticity; c) the
      ability of a range of stressors to enhance implicit fear conditioning, and to
      enhance the amygdaloid plasticity that underlies it.

PMID- 14584831
TI  - In vivo determination of knee kinematics in patients with a hamstring or patellar
      tendon ACL graft.
AB  - Video fluoroscopy was used to assess the in vivo kinematics for patients with a
      patellar-tendon-bone or double-looped semitendinosus gracilis anterior cruciate
      ligament (ACL) graft. Patients with a double-looped semitendinosus gracilis ACL
      graft experienced kinematic patterns more similar to the normal knee than
      patients with a patellar-tendon-bone reconstruction. Patients with a double
      looped semitendinosus gracilis reconstruction also experienced more anterior
      contact at full extension and throughout the flexion cycle than patients with a
      patellar-tendon-bone reconstruction, which resulted in patients with double
      looped semitendinosus gracilis grafts experiencing more posterior femoral
      rollback. Therefore, removal of the central third of the patella ligament leads
      to a decrease in quadriceps mechanism efficiency, which resulted in the more
      posterior contact positions demonstrated by the patients with patellar-tendon
      bone grafts in this study.

PMID- 14584830
TI  - Simultaneous ACL and PCL reconstruction.
AB  - The results of 11 patients who underwent simultaneous arthroscopically assisted
      anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL)
      reconstruction for acute (n=7) or chronic (n=4) multiligamentous knee injuries
      were reviewed. Seven patients were treated with a bone-patellar tendon-bone
      (BPTB) autograft for the ACL reconstruction and an Achilles allograft for the PCL
      reconstruction, three patients with ipsilateral/contralateral BPTB autografts,
      and one patient with BPTB allograft for ACL and Achilles allograft for PCL. Seven
      patients were operated on acutely (<3 months postinjury), and 4 were treated for
      chronic conditions. At follow-up, all patients were subjectively and functionally
      evaluated with a Lysholm Knee Scoring Scale. Average patient age at surgery was
      29 years, and average postoperative follow-up was 28.4 months. Average
      postoperative Lysholm score was 87.7 (range: 49-100). Four of 11 patients
      reported occasional mild pain, 2 occasional swelling, and 4 infrequent
      instability. No patient required a postoperative manipulation to regain his or
      her range of motion and 10 of the 11 returned to their previous activity level
      postoperatively. Of the 10 patients able to return for clinical examination, 2
      demonstrated a loss of flexion <5 degrees compared to the other side, 7
      demonstrated a mild postoperative posterior drawer at 90 degrees (6 at 1+, 1 at
      2+), 3 demonstrated a positive Lachman (grade 1), whereas no patient demonstrated
      any posterior lateral corner instability. The average anterior active difference
      on KT-1000 was 2.6 (range: 0-6). Simultaneous reconstruction of the ACL and PCL,
      although technically difficult, is feasible and yields good to excellent
      functional results.

PMID- 14584832
TI  - Patella baja after the modified Coventry-Maquet high tibial osteotomy.
AB  - This study assessed the Modified Coventry-Maquet technique for high tibial
      osteotomy with respect to the incidence of patella baja using the Insall-Salvati
      index. Twenty-seven high tibial osteotomies performed or supervised by a single
      surgeon (A.E.G.) between 1996 and 2000 were analyzed. Eight knees were excluded;
      the remaining 19 were evaluated. Mean patient age at surgery was 49 years, and
      the mean postoperative Insall-Salvati index was 0.83. This represented an average
      decrease in patellar height of 15% (P<.000001). The incidence of new-onset
      postoperative patella baja was 26% (5/19). Tibial posterior slope increased by an
      average of 4.3 degrees (P<.0001). Mean tibial tuberosity height decreased by an
      average of 8.9 mm (P<.0001). The mechanical axis was corrected by an average of
      11.9 degrees and loss of range of motion postoperatively was negligible. The
      correlation between tibial slope, tuberosity height, and patellar height was not
      significant. The modified Coventry-Maquet procedure achieved excellent valgus
      knee realignment while losing minimal range of motion and avoiding intra
      articular fracture and nonunion. This incidence of patella baja was comparable to
      most, and better than some, published series.

PMID- 14584828
TI  - Cycles of aberrant synaptic sprouting and neurodegeneration in Alzheimer's and
      dementia with Lewy bodies.
AB  - Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) are the most common
      neurodegenerative disorders affecting the elderly. The cognitive and motor
      deficits in these diseases are associated with the disruption of neuritic
      substructure, loss of synaptic contacts in selectively vulnerable circuitries,
      and aberrant sprouting. Where as in AD, accumulation of misfolded forms of Abeta
      triggers neurodegeneration, in DLB accumulation of alpha-synuclein might play a
      central role. The mechanisms by which oligomeric forms of these proteins might
      lead to cycles of synapse loss and aberrant sprouting are currently under
      investigation. Several possibilities are being considered, including
      mitochondrial damage, caspase activation, lysosomal leakage, fragmentation of the
      Golgi apparatus, interference with synaptic vesicle transport and function, and
      interference with gene transcription and signaling. Among them, recent lines of
      research support the possibility that alterations in signaling pathways such
      extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and
      p38 relevant to synaptic plasticity and cell survival might play a pivotal role.
      A wide range of cellular functions are affected by the accumulation of misfolded
      Abeta and alpha-synuclein; thus it is possible that a more fundamental cellular
      alteration may underlie the mechanisms of synaptic pathology in these disorders.
      Among them, one possibility is that scaffold proteins, such as caveolin and JNK
      interacting protein (JIP), which are necessary to integrate signaling pathways,
      are affected, leading to cycles of synapse loss and aberrant sprouting. This is
      significant because both caveolar dysfunction and altered axonal plasticity might
      be universally important in the pathogenesis of various neurodegenerative
      disorders, and therefore these signaling pathways might be common therapeutic
      targets for these devastating diseases.

PMID- 14584833
TI  - The relationship of lateral release and tourniquet deflation in total knee
      arthroplasty.
AB  - A total of 242 knees in 198 patients undergoing total knee arthroplasty were
      reviewed to evaluate the effect of tourniquet deflation on lateral release rates,
      possible variables associated with the need for lateral release, and adequacy of
      intraoperative evaluation on final radiographs. The need for lateral release was
      determined using the "no-thumbs" and "full contact" rules and visual evaluation.
      Lateral release was performed after tourniquet deflation. A total of 171 (71%)
      knees needed a lateral release before tourniquet deflation. After tourniquet
      deflation, only 53 (22%) required lateral release, representing a 69% reduction.
      Obesity was the only other significant factor in lateral release requirement.
      Based on the observations of this study, it is recommended that the need for
      lateral release be evaluated after tourniquet deflation. A 69% reduction in
      lateral release supports the hypothesis that tourniquet pressure has an effect on
      patellar tracking. Lateral release appears to be effective in restoring normal
      patellar tilt, and obesity increases its need.

PMID- 14584834
TI  - The long-term outcome of total knee patients with moderate loss of motion.
AB  - This study determined the outcome of total knee replacement (TKR) patients with
      moderate loss of motion who received no particular treatment. Twenty patients
      with an average arc of motion of 8 degrees-91 degrees of flexion 3 months
      postoperatively underwent 3-year follow-up. No formal treatment was given. All
      patients' range of motion and Knee Society scores improved over time. Most of the
      improvement occurred by 2 years. Patients with moderately stiff TKRs continue to
      improve over time without vigorous, prolonged physical therapy, manipulation, or
      bracing.

PMID- 14584835
TI  - Patellar tendon ossification treated with simple subcapsular excision.

PMID- 14584829
TI  - Motor enrichment and the induction of plasticity before or after brain injury.
AB  - Voluntary exercise, treadmill activity, skills training, and forced limb use have
      been utilized in animal studies to promote brain plasticity and functional
      change. Motor enrichment may prime the brain to respond more adaptively to
      injury, in part by upregulating trophic factors such as GDNF, FGF-2, or BDNF.
      Discontinuation of exercise in advance of brain injury may cause levels of
      trophic factor expression to plummet below baseline, which may leave the brain
      more vulnerable to degeneration. Underfeeding and motor enrichment induce
      remarkably similar molecular and cellular changes that could underlie their
      beneficial effects in the aged or injured brain. Exercise begun before focal
      ischemic injury increases BDNF and other defenses against cell death and can
      maintain or expand motor representations defined by cortical microstimulation.
      Interfering with BDNF synthesis causes the motor representations to recede or
      disappear. Injury to the brain, even in sedentary rats, causes a small, gradual
      increase in astrocytic expression of neurotrophic factors in both local and
      remote brain regions. The neurotrophic factors may inoculate those areas against
      further damage and enable brain repair and use-dependent synaptogenesis
      associated with recovery of function or compensatory motor learning. Plasticity
      mechanisms are particularly active during time-windows early after focal cortical
      damage or exposure to dopamine neurotoxins. Motor and cognitive impairments may
      contribute to self-imposed behavioral impoverishment, leading to a reduced
      plasticity. For slow degenerative models, early forced forelimb use or exercise
      has been shown to halt cell loss, whereas delayed rehabilitation training is
      ineffective and disuse is prodegenerative. However, it is possible that, in the
      chronic stages after brain injury, a regimen of exercise would reactivate
      mechanisms of plasticity and thus enhance rehabilitation targeting residual
      functional deficits.

PMID- 14584836
TI  - Extensor mechanism complications following total knee arthroplasty.
AB  - Patellofemoral complications are avoided by careful patient selection, proper
      implant design, and correct surgical technique. The patient with an extensor
      mechanism complication should be carefully evaluated for femoral and tibial
      component positioning, especially rotational alignment. Management of the
      extensor mechanism complication should be directed at its cause and may
      necessitate revision of the entire arthroplasty. Isolated revision of a patellar
      implant should only be performed once satisfactory alignment of the femoral and
      tibial components has been confirmed.

PMID- 14584837
TI  - Patellar instability in total knee arthroplasty.

PMID- 14584838
TI  - Patellar fracture following total knee arthroplasty.

PMID- 14584839
TI  - Patellar tendon and quadriceps tendon tears after total knee arthroplasty.

PMID- 14584840
TI  - Matched concurrent case-control study of risk factors for feather pecking in hens
      on free-range commercial farms in the UK.
AB  - 1. The aim of the study was to compare the management and husbandry of free-range
      flocks in the UK where feather pecking was either present (case) or absent
      (control). 2. One hundred flocks were enrolled into a concurrent case-control
      study: 50 where birds had recently started feather pecking, and 50 matched
      control flocks where birds of the same age had not started feather pecking. 3.
      Information was obtained from a detailed interview with the flock manager, and by
      direct inspection of the flock, house and range. 4. Initial univariate analyses
      revealed that case flocks were more likely to comprise ISA Brown than Lohmann,
      were more likely to be restricted from litter areas to prevent floor eggs, and
      were less likely to use the outside range. 5. Cluster analysis indicated that
      feather pecking was not associated with any particular husbandry system. 6. The
      only influential risk factor significant in the multivariable conditional
      logistic regression analysis was use of the outdoor range. The risk of feather
      pecking was reduced 9-fold in flocks where more than 20% of birds used the range
      on sunny days (odds ratio = 0.12). Use of the range was positively associated
      with the presence of trees and/or hedges on the range.

PMID- 14584841
TI  - Computer-assisted image analysis to quantify daily growth rates of broiler
      chickens.
AB  - 1. The objective was to investigate the possibility of detecting daily body
      weight changes of broiler chickens with computer-assisted image analysis. 2. The
      experiment included 50 broiler chickens reared under commercial conditions. Ten
      out of 50 chickens were randomly selected and video recorded (upper view) 18
      times during the 42-d growing period. The number of surface and periphery pixels
      from the images was used to derive a relationship between body dimension and live
      weight. 3. The relative error in weight estimation, expressed in terms of the
      standard deviation of the residuals from image surface data was 10%, while it was
      found to be 15% for the image periphery data. 4. Image-processing systems could
      be developed to assist the farmer in making important management and marketing
      decisions.

PMID- 14584842
TI  - Effect of artificial structuring on the use of laying hen runs in a free-range
      system.
AB  - 1. This study examined whether a free range with roofed boxes with sand to
      structure the hen run had an effect on the numbers of hens going outside and on
      the distribution of the hens in the hen run. 2. On a poultry farm with 8 flocks
      of laying hens of roughly 500 birds per flock, each flock was observed with and
      without roofed boxes with sand. 3. There was no difference in the number of hens
      on free range with and without roofed boxes but there was an influence on the
      distribution. 4. In free range with structures there was a higher percentage of
      the hens outside in the furthest quarter where the structures were located. 5. We
      conclude that structures in the free range have an effect on the distribution of
      laying hens.

PMID- 14584843
TI  - Eating behaviour, and preprandial and postprandial correlations in male broiler
      and layer chickens.
AB  - 1. It has been suggested that broiler chickens have a disturbed satiety and
      hunger mechanism. The satiety mechanism for eating can be expressed as the
      positive correlation between meal length and the length of the preceding
      (preprandial) interval; the hunger mechanism for eating as the positive
      correlation between meal length and the length of the succeeding (postprandial)
      interval. An experiment was conducted to investigate eating behaviour of male
      broiler and layer chickens by measuring meal and interval lengths. 2. Eight male
      broilers and 8 male layer chickens were housed individually and visually isolated
      in floor pens (1 m2/pen) on wood shavings. From 4 to 7 weeks of age, eating
      behaviour of each bird was recorded for 3 h in two conditions each week. In the
      first condition, the birds were not deprived from feed. In the second condition,
      they were 24-h food deprived and feed was provided just before the observation
      started. Preprandial and postprandial correlations were calculated based on data
      of the non-deprived condition. Before and after each observation bird and feeder
      were weighed to measure weight gain and feed consumption during observation. 3.
      Under the non-deprived condition, the broilers spent initially more, but at a
      later age less time on eating. The broilers had fewer meals per hour, consumed
      more feed per hour, and had longer meal and interval lengths than the layer
      chickens. After 24-h feed deprivation, the broilers had a longer first meal,
      consumed more feed per hour and spent more time on eating than the layer
      chickens. Significant preprandial correlations but no postprandial correlations
      were found in the broilers. In the layer chickens, both significant preprandial
      and postprandial correlations were found. This indicates that for regulating
      eating behaviour, the satiety mechanism dominates the hunger mechanism in
      broilers, and satiety and hunger mechanisms are equally involved in layer
      chickens. 4. The typical eating behaviour of broilers and the calculated
      preprandial and postprandial correlations have given new indications that hunger
      and satiety mechanisms in broilers have changed compared with layer chickens. In
      broilers, there is no lower set point, but only an upper set point for
      controlling eating behaviour, which suggests that broilers eat to their maximal
      physical capacity.

PMID- 14584844
TI  - Effect of heat stress on oxidative stress, lipid peroxidation and some stress
      parameters in broilers.
AB  - 1. This study was conducted to determine the effects of heat stress on
      fearfulness, leucocyte components, oxidative stress and lipid peroxidation in two
      commercial broiler strains, Cobb (C) and Ross (R). 2. At 36 and 37 d of age birds
      were exposed to 38 +/- 1 degree C for 3 h. Rectal temperatures, duration of tonic
      immobility (TI), haematocrit values, proportions of leucocyte components
      (heterophil, lymphocyte, basophil, eosinophil, monocyte), malondialdehyde (MDA)
      concentrations and antioxidant enzyme activities (CAT, SOD, GPx) of all the birds
      were determined, before and after heat treatment. 3. Rectal temperatures
      increased and haematocrit values decreased in birds exposed to heat stress. Heat
      stress caused a significant increase in heterophil/lymphocyte and in basophil
      ratios. 4. Exposing birds to heat stress increased duration of TI, suggesting
      heat-stressed birds tended to be more fearful. 5. Heat stress resulted in a
      significant Genotype x Treatment interaction for MDA concentration. CAT, SOD and
      GPx activities; MDA concentrations in heat-stressed R strain birds were greater
      than in heat-stressed C strain birds.

PMID- 14584845
TI  - Observations on the distribution and persistence of Salmonella enterica serovar
      enteritidis phage type 29 on a cage layer farm before and after the use of
      competitive exclusion treatment.
AB  - 1. A continuously occupied cage layer house, which had been linked with a human
      outbreak of Salmonella Enteritidis PT29, was investigated to assess the
      distribution of contamination and the options for control. 2. The presence and
      persistence of Salmonella before and after application of competitive exclusion
      (CE) treatment was investigated by culturing samples from faeces, the
      environment, spent hens and eggs, and use of an ELISA to detect egg yolk
      antibodies. 3. A high prevalence of Salmonella was found in faecal and
      environmental samples before CE treatment was used but this reduced to minimal
      levels after treatment. 4. Egg yolk antibody assay suggested that although
      treated birds showed reduced excretion of Salmonella there was no difference
      between these and non-treated birds in terms of seroprevalence. 5. Contamination
      of the egg packing plant disappeared following CE. 6. Chicks and pullets in
      separate accommodation on site remained Salmonella free throughout despite no
      precautions being taken to avoid transmission of infection from the laying flock.
      7. The rapid and substantial reduction in Salmonella in faeces, birds and the
      environment following the introduction of CE treatment suggests that further
      controlled field studies would be justified.

PMID- 14584846
TI  - Effects of aflatoxin B1 on the development of the bursa of Fabricius and blood
      lymphocyte acid phosphatase of the chicken.
AB  - 1. In this study, embryotoxicity and effects of in ovo administration of
      aflatoxin B1 (AFB1) on the embryonic development of the bursa of Fabricius were
      determined in fertilised chicken eggs by histological methods and histochemical
      demonstration of acid phosphatase (ACP-ase) enzyme. Peripheral blood lymphocyte
      percentages were also estimated. 2. Embryonic stages were determined according to
      the Hamburger-Hamilton (H-H) scale. Mortality rates increased in AFB1-injected
      groups in a dose-dependent manner. Embryonic deaths were concentrated at H-H 31
      in the 5 ng AFB1/egg group while the deaths were highest at H-H 25 in the 10 and
      20 ng AFB1/egg groups. In the 40ng AFB1/egg group, embryonic deaths mostly
      occurred during the first 70 to 72 h of incubation (H-H 20). 3. Bursal
      development was quite similar at d 7 of incubation in control and all
      experimental groups although development had been substantially impaired and
      retarded at d 10 of incubation in 10, 20 and 40 ng AFB1/egg groups. A gradual
      decrease of ACP-ase positive lymphocyte numbers was observed with increasing AFB1
      doses. The chicks in AFB1-treated groups hatched with poorly developed bursae
      compared with those of the controls. However, proportions of ACP-ase positive
      lymphocytes substantially increased at hatch and at 21 d of incubation all groups
      had similar numbers. 4. The results revealed that breeder diets should be
      investigated for aflatoxins and specifically AFB1, in cases of low hatchability
      and flock immunity, because low concentration of AFB1 transferred into the
      fertilised eggs might be the cause of serious problems.

PMID- 14584847
TI  - Microbial cross-contamination by airborne dispersion and contagion during
      defeathering of poultry.
AB  - 1. A readily identifiable strain of Escherichia coli K12 was used as a 'marker'
      organism to determine the sources, routes and patterns of microbial cross
      contamination during mechanical defeathering of broiler chicken carcases. 2.
      Inoculation of scald water with the marker organism led to a relatively even
      pattern of carcase contamination during subsequent defeathering. Microbial cross
      contamination was greater by this route of inoculation than by either surface
      inoculation of a 'seeder' carcase or oral inoculation of a live bird one day
      before slaughter. 3. Dispersal of the marker organism was strongly influenced by
      the mechanical action of the defeathering machines. Forward transmission of the
      marker occurred by aerosol or large airborne droplets and particulates such as
      feathers. Moving carcases through the defeathering machines when these were non
      operational clearly reduced backward transmission of the marker. 4. Although
      microbial dispersal was unaffected by increasing the spacing between individual
      carcases or installing a water curtain at the entry and exit of the defeathering
      machines, shielding of carcases with aluminium baffles reduced counts of the
      marker organism from contaminated carcases by > 90%. 5. The results imply that
      microbial cross-contamination of broiler chicken carcases during defeathering
      occurs mainly via the airborne route, which could be contained by physical means.

PMID- 14584848
TI  - Physical characteristics and chemical composition of Lesser Rhea (Pterocnemia
      pennata) eggs from farmed populations.
AB  - 1. Eggs from 4 farmed populations of Lesser Rhea (Pterocnemia pennata) were
      studied to determine their physical and chemical characteristics. 2. None of the
      physical variables (weight of whole egg, yolk, albumen and shell; proportion of
      yolk based on egg content; proportion of shell based on entire egg weight;
      volume; density) showed significant differences between populations. 3. Among
      chemical variables, moisture, both saturated fatty acids (palmitic 16:0 and
      stearic 18:0), one monounsaturated fatty acid (palmitoleic 16:1), and one
      polyunsaturated fatty acid (arachidonic 20:4), did not differ between
      populations, whereas other variables (protein, lipid and ash contents; fatty
      acids: oleic 18:1, linoleic 18:2, linolenic 18:3; PUFA; PUFA/SFA; cholesterol)
      differed significantly.

PMID- 14584849
TI  - Reducing the phosphorus concentration in diets for turkeys between 10 and 22
      weeks of age.
AB  - 1. An experiment lasting for 13 weeks was started at the beginning of week 10
      with male turkeys weighing 5.38 kg. The experiment comprised three subsequent
      periods with adjusted metabolisable energy (ME) and nutrient concentrations from
      weeks 10 to 13, 14 to 17, and 18 to 22. Seven pens of 12 birds each were
      allocated to each of 5 treatments. Treatments differed in dietary phosphorus
      concentration and phytase supplementation (500 U/kg) only. Total phosphorus
      varied between treatments from 4.9 to 8.0 g/kg (weeks 10 to 13), from 4.4 to 7.5
      g/kg (weeks 14 to 17) and from 3.5 to 7.0 g/kg (weeks 18 to 22). Phosphorus
      concentration was adjusted by different inclusions of monocalcium phosphate.
      Diets were pelleted and offered ad libitum. 2. A final body weight of, on
      average, 22.3 kg was achieved at the end of week 22. Body weight gain, feed
      consumption, feed conversion, toe ash, toe phosphorus and toe calcium were not
      significantly affected by dietary phosphorus concentration. There was no
      indication of an effect on mortality or on broken or deformed bones. 3.
      Phosphorus concentrations (g/kg diet) of 5.9, 5.4 and 4.4 without microbial
      phytase and of 4.9, 4.4 and 3.5 with microbial phytase, respectively, were
      sufficient in the three periods. As compared with the control, a reduction in
      phosphorus excretion of turkeys by 0.4 without phytase and by 0.5 with phytase
      was achieved without negative effects on turkeys. 4. Because the data demonstrate
      the great potential for a reduction in dietary phosphorus concentration, detailed
      requirement and availability studies with turkeys should follow.

PMID- 14584850
TI  - The effect of dietary energy and protein levels on production in breeding female
      ostriches.
AB  - 1. In a study spanning two breeding seasons, we assessed the effect of different
      dietary energy and protein levels on body mass, body condition, and egg
      production of female ostriches. 2. During the first breeding season, groups were
      given diets with energy concentrations of 8.5, 9.5 and 10.5 MJ/kg dry mass (DM)
      metabolisable energy (ME) and protein concentrations of 135, 150 and 165 g/kg. In
      the second breeding season, groups were given diets with ME of 7.5, 8.5 and 9.5
      MJ/kg and protein contents of 105, 120 and 135 g/kg. 3. Body mass of birds on
      diets of 7.5 and 8.5 MJ/kg ME decreased significantly in the course of the
      breeding season compared with birds fed on diets with higher energy contents and
      body measurements decreased, suggesting a loss of body condition. 4. Females fed
      on diets containing only 7.5 MJ/kg ME produced significantly fewer eggs at
      significantly longer intervals, resulting in fewer chicks hatched. 5. There was
      no significant difference in egg mass, initial chick mass, chick survival to one
      month of age and body mass of chicks at one month. 6. Dietary protein
      concentrations had no effect on egg production, egg mass, hatchability, initial
      chick mass, chick survival or chick mass at one month old. 7. The female
      ostriches regained their original body mass during the 4-month rest period
      between breeding seasons, but significant differences in some parameters during
      the second breeding season suggest that they may not have fully recovered their
      body condition. 8. A dietary energy content of 7.5 MJ/kg proved to have an
      adverse effect on egg production by breeding female ostriches, and it may be
      concluded from this study that a diet containing 8.5 MJ ME/kg DM and 105 g/kg
      protein should be regarded as the minimum that can be used for breeding female
      ostriches without compromising egg production.

PMID- 14584851
TI  - Method for collecting semen from the ostrich (Struthio camelus) and some of its
      quantitative and qualitative characteristics.
AB  - 1. Four methods of semen collecting that involved interruption of mating in two
      breeding ostrich pairs were tested: an artificial vagina was tested without
      promising results; the funnel method, in which a funnel was placed under the
      phallus of the tested male immediately after mating allowing semen drips to be
      collected; the vacuum method, using a turkey semen collector, inserted into the
      seminal canal; and the tube method, conducted by placing a test tube inside the
      seminal canal, allowing semen to enter by gravity. 2. For the funnel, vacuum and
      tube methods, respectively, average semen volume was 0.1 +/- 0.02, 1.12 +/- 0.22,
      and 0.58 +/- 0.13 ml, sperm concentration was 0.66 +/- 0.14, 2.35 +/- 0.26, and
      2.13 +/- 0.27 x 10(9) cells/ml, and percentage of abnormal cells was 5.82 +/-
      1.79%, 4.68 +/- 1.19%, and 7.09 +/- 1.72%. 3. Semen characteristics varied
      throughout the reproductive season reaching peak concentration in June-July. 4.
      The vacuum method proved to be the most efficient and was a low stress, restraint
      free method for collecting ostrich semen.

PMID- 14584852
TI  - Effect of canthaxanthin content of the maternal diet on the antioxidant system of
      the developing chick.
AB  - 1. Effects of canthaxanthin supplementation of the maternal diet on the
      antioxidant system of the developing chick were investigated. 2. Three hundred
      and twenty female broiler breeder birds were housed in one of 4 controlled
      environment rooms with 3 replicates for all treatments, with the exception of the
      control treatment of which there were 4 replicates. All birds received one of 5
      diets: control low xanthophyll diet, or the same diet supplemented with 3, 6, 12
      or 24 mg/kg canthaxanthin in the form of Carophyll Red. At 30 weeks of age 60
      eggs from each of the 5 groups were incubated. At d 16 of the embryo development,
      at d 1 and d 7 posthatch tissue samples were collected and analysed by HPLC-based
      methods. 3. Canthaxanthin accumulation in the egg yolk was proportional to
      dietary content. Furthermore, at 12 to 24 mg/kg canthaxanthin was associated with
      an increase in gamma-tocopherol concentration in the egg yolk. Canthaxanthin was
      transferred from the egg yolk to the developing embryo and, as a result, its
      concentration in the liver of the embryo at 16 and in 1-d-old chicks was
      increased. Even at d 7 posthatch canthaxanthin concentration in the chicken liver
      was elevated. 4. Canthaxanthin supplementation of the maternal diet at 12 mg/kg
      was associated with an increased alpha-tocopherol concentration in the liver of 1
      d-old chicks and resulted in decreased tissue susceptibility to lipid
      peroxidation. 5. Canthaxanthin supplementation at 6 to 24 mg/kg was also
      associated with a delay in alpha-tocopherol depletion from the liver for 7-d
      posthatch. As a result of the increased canthaxanthin and vitamin E
      concentrations in the liver of 7-d-old chicks, tissue susceptibility to lipid
      peroxidation decreased. 6. The results support an idea that dietary carotenoids
      can modulate antioxidant systems of the developing chicken.

PMID- 14584853
TI  - L-canavanine inhibits L-arginine uptake by broiler chicken intestinal brush
      border membrane vesicles.
AB  - 1. Intestinal brush border membrane vesicles (BBMV) were prepared from 3-week-old
      broiler chickens. 2. Electron microscopy of the BBMV fraction showed single
      membrane vesicles of different sizes with no electron dense material inside. No
      other organelles were observed. The sucrase and maltase activities were enriched
      by factors of 16 and 18, respectively, in the BBMV fraction in comparison with
      the homogenate. On the other hand, the Na+/K+-ATPase sensitivity to ouabain was
      increased by a factor of 0.8. 3. The BBMV showed a maximum L-[14C]-arginine
      uptake (944.9 +/- 22.9 pmoles/mg protein) at 45 s and thereafter it declined
      slowly. In the presence of 0.5 mM L-canavanine, the L-[14C]-arginine uptake by
      BBMV was reduced by 43.6% at 45 s. 4. It is concluded that L-canavanine inhibits
      L-arginine Na+-dependent transport across the enterocyte apical membrane in a
      highly purified intestinal BBMV from broiler chickens.

PMID- 14584854
TI  - Comparison of the coagulation profile of fatty liver haemorrhagic syndrome
      susceptible laying hens and normal laying hens.
AB  - 1. The rate of thrombin generation in plasma from Fatty Liver Haemorrhagic
      Syndrome-susceptible laying hens (FLHS, UCD-003) is more rapid than in plasma
      from age-matched normal Single Comb White Leghorn (SCWL) laying hens. 2. The rate
      of thrombin generation in plasma was determined by measuring the biological
      activity of the specific coagulation proteins, Factors V, VII, VIII, IX and X. 3.
      The higher activity of Factors V, VII and X in FLHS-susceptible laying hens
      compared with normal SCWL hens remained consistent after plasma lipid
      concentrations were reduced. 4. Analysis of the fatty acid composition of plasma
      phospholipids showed that in normal SCWL laying hens phosphatidylethanolamine
      contained C18:3n3 whereas it contained C20:3n3 in FLHS-susceptible laying hens.
      5. The results suggest that alterations in the composition of the phospholipids
      that are essential cofactors in the biochemical reactions involved in thrombin
      generation may be a contributing factor in the development of FLHS.

PMID- 14584855
TI  - Photorefractoriness in broiler breeders: sexual maturity and egg production
      evidence.
AB  - 1. Photorefractoriness was assessed in two lines of broiler breeders. In one
      trial, male-line and female-line pullets were reared on the floor and transferred
      to individual cages at 15 weeks. Birds were either maintained on 8-, 11- or 16-h
      photoperiods or transferred from 8- to 16-h photoperiods at 67 or 124 d. In the
      second trial, female-line pullets were concurrently housed in the same rearing
      facilities as trial 1 and transferred to adult floor-pens at 12 weeks. These
      birds were either maintained on 11- or 16-h photoperiods or transferred from 8-
      to 11-h or from 8- to 16-h photoperiods at 140 d. 2. In the cages, male-line and
      female-line birds responded similarly to the lighting treatments, but with the
      male-line maturing 1 to 2 weeks later than the female-line in each case. Birds on
      constant 11-h photoperiods matured 3 to 8 d earlier than constant 8-h birds, but
      3 weeks earlier than constant 16-h birds. Birds photostimulated at 67 d matured
      at a similar time to constant 16-h birds, but almost 7 weeks later than those
      transferred from 8 to 16 h at 124 d. In the floor facilities, constant 11-h birds
      matured 3 weeks earlier than constant 16-h birds, but almost 2 weeks later than
      either of the photostimulated groups. Birds transferred from 8 to 16 h matured 4d
      earlier than those transferred from 8 to 11 h. 3. Caged birds maintained on 16 h
      or transferred from 8 to 16 h at 67 d laid at least 24 fewer eggs, and had more
      hens not laying at 58 weeks, than birds maintained on 11-h days or those
      transferred from 8 to 16 h at 124 d. In the floor-pens, constant 11-h and both
      photostimulated groups produced about 20 more eggs to 56 weeks of age than the
      constant 16-h controls. 4. Collectively, these findings indicate that
      conventionally managed broiler breeders exhibit photorefractoriness.
      Additionally, a combination of photorefractoriness and controlled feeding appears
      to prevent broiler breeders from being photoresponsive until at least 10 weeks of
      age, and to cause some individuals still to be photoperiodically non-responsive
      at 18 weeks.

PMID- 14584856
TI  - Preparation of fowl testes as recipient organs to germ-line chimeras by means of
      gamma-radiation.
AB  - 1. The aim of the study was to investigate the possibility of preparing adult
      fowl testes for the production of exogenous germ-lines by eradication of
      recipient spermatogenesis using gamma-radiation. 2. A comparison between several
      radiation therapy treatments (based on 60Co isotope) of male testes was conducted
      using gamma-rays of 18, 22 and 26 Gy in a single dose or repeated doses of 5 x 8
      Gy over a 15-d period. Sperm concentration and motility were determined after
      each treatment. 3. Altered spermatogenesis was observed after a single treatment
      dose of 18 Gy, while single doses of 26 Gy were followed by reduced sperm numbers
      (from 22 x 10(9) to 31 x 10(6) sperm/ml) within 60 to 100 d after treatment.
      After a single treatment of 26 Gy sperm motility was reduced by 50%. In contrast,
      a fractionated treatment (5 x 8 Gy) with gamma-rays halted spermatogenesis 39 d
      after the distribution of the first 8 Gy dose. 4. Observations of the
      seminiferous tubules by electron microscopy performed 12 months after this
      treatment confirmed that moderate doses of gamma-rays (8 Gy) distributed
      repeatedly (5 x) over a limited period (15 d) sterilise adult fowl testes but
      maintain morphologically normal somatic (Leydig and Sertoli) cell populations.

PMID- 14584857
TI  - Functional development and intestinal absorption in the young poult.
AB  - 1. Absorption, secretion of digestive enzymes and intestinal morphology were
      determined in poults from hatching to 19 d. 2. Oleic acid was approximately 80%
      absorbed at hatch and this changed little with age and was not influenced by
      fasting. In contrast, glucose and methionine were 48 to 56% absorbed at hatch and
      this increased to 75 to 80% at 4 d; however, this increase in absorption was
      inhibited by fasting. Percentage absorption of protein did not change between 5
      and 19 d, whereas absolute uptake of fat and protein and net secretion of
      digestive enzymes and fatty acids and N to the duodenum increased with age and
      body weight (BW). 3. The length and diameter and villus size in the small
      intestines increased rapidly after hatch whereas the number of villi per cross
      section did not change with age. Duodenum and ileum surface area reached a
      plateau after 11 d whereas jejunal surface area continued to increase until 19 d.
      Duodenal and ileal surface area were not related to BW, but jejunal surface area
      was significantly correlated. 4. While the major part of the absorption occurred
      in the duodenum and upper jejunum, uptake of both protein and fat increased in
      the distal segments of the small intestine with age. Overall absorption of both
      fat and protein was correlated with BW. 5. It appears that in the posthatch poult
      intestinal surface area is not a limiting factor in growth, which was correlated
      with digestive secretions, fat and protein uptake.

PMID- 14584859
TI  - Periodontal regeneration with a combination of enamel matrix proteins and
      autogenous bone grafting.
AB  - BACKGROUND: Attempts to stimulate periodontal regeneration in the past have
      focused on either filling the defect with some type of material or providing a
      space for host cells to repopulate the site and elicit new tissue. In some cases,
      these approaches have been combined with the assumption that the filler material
      will help maintain the space necessary for the host cells to invade the area.
      Growth stimulating substances such as growth factors and other proteins have also
      been used to encourage periodontal tissue regeneration and histological
      evaluation supports the use of these substances. Thus, the role for and the
      necessity of a certain amount of space maintenance for periodontal regeneration
      is not exactly understood. In addition, it is not known if there is some critical
      size required for space maintenance or for exactly how long the space must be
      maintained in order for the host cells to stimulate new cementum, periodontal
      ligament, and bone. The goal of this study was to evaluate periodontal
      regeneration in intrabony defects of various sizes treated with a combination of
      enamel matrix proteins and autogenous bone graft. METHODS: Periodontal defects
      ranging in size from 1 to 6 mm were randomized and created bilaterally beside
      three teeth in the mandibles of baboons. Plaque was allowed to accumulate around
      wire ligatures placed into the defects. After 2 months, the wire ligatures were
      removed, the teeth and roots scaled and root planed, and a notch was placed with
      a chisel at the base of the defect. On one side of the mandible, neutral ethylene
      diamine tetracetic acid and enamel matrix derivative (EMD) were first used to
      treat the defect. Autogenous bone taken from the same surgical site was treated
      with enamel matrix derivative in a dampen dish and then added to the EMD-treated
      defects. The other side of the mandible served as control with neutral ethylene
      diamine tetracetic acid and scaling and root planing. Flaps were sutured and the
      animals were allowed to heal without oral hygiene procedures. After 5 months, the
      animals were sacrificed and the teeth were processed for histological evaluation.
      RESULTS: The results revealed new cementum, periodontal ligament with Sharpey's
      fibers, and new bone tissue similar to native periodontal tissues. Remnants of
      the autogenous bone chips were still present at this 5-month post-healing period.
      Thus periodontal regeneration occurred in all sizes of the periodontal defects.
      In general, EMD plus autogenous graft treatment resulted in greater tissue
      formation than controls. In fact, in many cases, very dramatic tissue formation
      occurred far coronal to the base of the defects in the EMD plus autogenous graft
      treated lesions. In addition, horizontal bone fill occurred in the defects and
      was prominent in the 4 or 6 mm wide lesions. When evaluating the combined 1 and 2
      mm defects, the height of new cementum with EMD plus graft was 3.88 mm versus
      2.03 mm in the controls, a statistically significant (P < 0.005) difference. In
      the wider (4 and 6 mm) lesions, this difference was not significant and was much
      less between treated and control lesions with 2.78 and 2.57 mm of new cementum
      respectively. In the case of new bone height, in the smaller lesions EMD plus
      graft resulted in 4.00 mm new bone versus 2.22 mm in the controls, again a
      statistically significant (P < 0.005) difference. In the larger lesions, EMD plus
      autogenous bone graft had 3.24 mm new bone height compared to 2.71 mm in the
      controls, a difference that was not statistically significant. Additionally, in
      the smaller lesions, new cementum width at the level of the notch was twice as
      great (statistically significant, P < 0.015) in the EMD plus graft sites compared
      to control. The width of the periodontal ligament at the coronal aspect of the
      new bone tissue was similar in the smaller lesions between treated and control
      sites. The results from the wider defects must be interpreted cautiously as the
      interproximal bone heights were remodeled adjacent to the wider defects and
      likely limited the potential for regeneration. CONCLUSIONS: The combination of
      enamel matrix derivative plus autogenous bone graft stimulated statistically
      significant periodontal regeneration in the more narrow 1 and 2 mm lesions. No
      statistically significant difference was observed in the wider 4 and 6 mm
      lesions. In many cases, dramatic amounts of new cementum, Sharpey's fibers,
      periodontal ligament, and bone tissue were formed far above the notch placed at
      the base of the contaminated defects. This was especially significant considering
      the width of some of the defects and the fact that no oral hygiene was performed
      over the 5-month healing period. This periodontal regeneration occurred in the
      absence of exogenous growth factors or barrier membranes. In summary, the
      combination of enamel matrix derivative and autogenous bone represents a
      therapeutic combination that can be highly effective in stimulating significant
      amounts of periodontal regeneration.

PMID- 14584858
TI  - Factors influencing the outcome of regenerative therapy in mandibular Class II
      furcations: Part I.
AB  - BACKGROUND: Factors influencing the outcome of regenerative therapy of Class II
      furcations are incompletely and poorly understood. The purpose of this 24-month
      prospective study was to examine the relationship of patient-, site-, and
      treatment-related factors to the clinical closure of randomly selected mandibular
      Class II furcations. Results of therapy were evaluated at 1 and 2 years
      postoperatively. One-year outcome data are presented in this report. METHODS: A
      total of 43 otherwise healthy individuals with chronic periodontitis (26 male, 17
      female), 36 to 70 years of age, completed the 12-month evaluation of the study.
      Entry criteria included clinical and radiographic evidence of two or more
      mandibular facial Class II furcation defects (> or = 3 mm horizontal probing
      depth). Surgical therapy was completed by four periodontists (two each) in either
      a university clinic or private practice. Each patient contributed two furcation
      defects that were treated by combination therapy using an expanded
      polytetrafluoroethylene (ePTFE) membrane and demineralized freeze-dried bone
      allograft (DFDBA). Clinical measurements included a gingival index, plaque index,
      mobility, and, referencing an occlusal stent, probing depth (PD), probing
      attachment level-vertical (PAL-V), and probing attachment level-horizontal (PAL
      H). Multiple linear measurements were recorded for each site clinically and after
      surgical debridement to characterize defect morphology, root configuration, and
      barrier placement. Defect volume was computed mathematically. Postsurgical
      maintenance care was provided at 1 to 2, 4, 6, and 8 weeks, and then biweekly
      until 3 months, with subsequent supportive periodontal maintenance visits at 3
      month intervals. The clinical status of the furcation (open or closed), measured
      by a non-treating periodontist at 1 and 2 years, was the primary outcome measure.
      The association of patient-related factors (e.g., smoking), site-related factors
      (e.g., root configuration and defect morphology), and treatment-related factors
      (e.g., membrane exposure) to clinical status of furcations was assessed using
      random effects hierarchical logistic regression analysis, controlling for design
      and demographic variables. Non-parametric analysis was used for specific group
      comparisons. RESULTS: Complete clinical closure was achieved in 74% of all sites.
      Of the residual furcation defects, 68% were reduced to Class I. No defects
      progressed to Class III. Significant improvements in mean PD and PAL-V were
      obtained following surgical therapy. Although the proportion of sites
      demonstrating complete furcation closure was comparable for smokers and non
      smokers, the proportion of Class II residual defects was significantly higher
      among smokers than non-smokers (62.5% versus 14.3%, respectively). Increases in
      presurgical PAL-H were associated with monotonic decreases in the percentage of
      sites demonstrating complete clinical closure, with only 53% of lesions > or = 5
      mm responding with complete closure. Similarly, significant reductions in the
      frequency of clinical closure were associated with increases in the distance
      between the roof of furcation and crest of bone, roof of furcation and base of
      defect, depth of horizontal defect, and divergence of roots at the crest of bone.
      CONCLUSIONS: The successful clinical closure of Class II furcations was
      achievable at 1 year following combination therapy with an ePTFE membrane and
      DFDBA. The highest frequency of clinical furcation closure was observed in early
      Class II defects. Furcations with vertical or horizontal bone loss of 5 mm or
      greater responded with the lowest frequency of complete clinical closure.
      Nevertheless, complete furcation closure was achievable in 50% of molars with
      extensive bone loss. Also, 15 out of 22 (68%) of all residual defects were
      reduced to Class I and only seven (8%) failed to improve, demonstrating that
      successful clinical resolution of advanced defects remains an attainable goal.

PMID- 14584860
TI  - Periodontal regeneration in humans using recombinant human platelet-derived
      growth factor-BB (rhPDGF-BB) and allogenic bone.
AB  - BACKGROUND: Purified recombinant human platelet-derived growth factor BB (rhPDGF
      BB) is a potent wound healing growth factor and stimulator of the proliferation
      and recruitment of both periodontal ligament (PDL) and bone cells. The hypothesis
      tested in this study was that application of rhPDGF-BB incorporated in bone
      allograft would induce regeneration of a complete new attachment apparatus,
      including bone, periodontal ligament, and cementum in human interproximal
      intrabony defects and molar Class II furcation lesions. METHODS: Nine adult
      patients (15 sites) with advanced periodontitis exhibiting at least one tooth
      requiring extraction due to an extensive interproximal intrabony and/or molar
      Class II furcation defect were entered into the study. Eleven defects were
      randomly selected to receive rhPDGF-BB. Following full-thickness flap reflection
      and initial debridement, the tooth roots were notched at the apical extent of the
      calculus, the osseous defects were thoroughly debrided, and the tooth root(s)
      were planed/prepared. The osseous defects were then filled with demineralized
      freeze-dried bone allograft (DFDBA) saturated with one of three concentrations of
      rhPDGF-BB (0.5 mg/ml, 1.0 mg/ml, or 5.0 mg/ml). Concurrently, four interproximal
      defects were treated with a well accepted commercially available graft (anorganic
      bovine bone in collagen, ABB-C) and a bilayer collagen membrane. Radiographs,
      clinical probing depths, and attachment levels were obtained preoperatively (at
      baseline) and 9 months later. At 9 months postoperatively, the study tooth and
      surrounding tissues were removed en bloc. Clinical and radiographic data were
      analyzed for change from baseline by defect type and PDGF concentration. The
      histologic specimens were analyzed for the presence of regeneration of a complete
      new attachment apparatus coronal to the reference notch. RESULTS: The post
      surgical wound rapidly healed and was characterized by firm, pink gingivae within
      7 to 10 days of surgery. There were no unfavorable tissue reactions or other
      safety concerns associated with the treatments throughout the course of the
      study. In rhPDGF/allograft sites, the vertical probing depth (vPD) reduction for
      interproximal defects was 6.42 +/- 1.69 mm (mean +/- SD) and clinical attachment
      level (CAL) gain was 6.17 +/- 1.94 mm (both P < 0.01). Radiographic fill was 2.14
      +/- 0.85 mm. Sites filled with ABB-C had a PD reduction and CAL gain of 5.75 +/-
      0.5 and 5.25 +/- 1.71, respectively. Furcation defects treated with
      rhPDGF/allograft exhibited a mean horizontal and vertical PD reduction of 3.40 +/
      0.55 mm (P < 0.001) and 4.00 +/- 1.58 mm (P < 0.005), respectively. The CAL gain
      for furcation defects was 3.2 +/- 2.17 mm (P < 0.030). Histologic evaluation
      revealed regeneration of a complete periodontal attachment apparatus, including
      new cementum, PDL, and bone coronal to the root notch in four of the six
      interproximal defects and all evaluable (four of four) furcation defects treated
      with PDGF. Two of the four interproximal intrabony defects treated with ABB-C and
      membrane exhibited regeneration. CONCLUSIONS: Use of purified rhPDGF-BB mixed
      with bone allograft results in robust periodontal regeneration in both Class II
      furcations and interproximal intrabony defects. This is the first report of
      periodontal regeneration demonstrated histologically in human Class II furcation
      defects.

PMID- 14584861
TI  - Pain experienced by patients during periodontal maintenance.
AB  - BACKGROUND: The aims of this study were to determine: 1) the degree of pain
      experienced by patients during probing and debridement; 2) whether the treating
      hygienists could estimate the degree of pain experienced by the patients; and 3)
      whether the patients' pain responses could be predicted by factors such as the
      patients' age, gender, number of residual periodontal lesions, and answers to a
      questionnaire on dental anxiety. METHODS: Prior to periodontal maintenance
      procedures, two groups of 20 adult patients to be treated by two hygienists
      completed an anxiety questionnaire. Subsequently, measurements of probing depths
      were performed, followed by pain ratings by each patient using a visual analog
      scale (VAS). The hygienists also completed a VAS, estimating the pain level they
      perceived their patient to have experienced. The same protocol was repeated for
      instrumentation (debridement). RESULTS: Most patients showed low pain responses
      to both probing and instrumentation. However, using an arbitrary threshold of VAS
      > or = 40 mm, 20% to 33% of the patients had a significant pain experience. The
      hygienists were quite accurate in their relative estimates of their patients'
      pain experiences. Regression analyses disclosed that significant portions of the
      pain responses could be predicted by the patients' answers to one of the dental
      anxiety questions. CONCLUSIONS: Recognition of patients who are likely to
      experience significant pain during periodontal treatment may be facilitated by
      the use of one question on dental anxiety. During treatment, the ability to gauge
      and respond to patients' pain experiences would seem to be an important component
      of a therapist's clinical skills.

PMID- 14584862
TI  - Impact of increased occlusal contact, interleukin-1 genotype, and periodontitis
      severity on gingival crevicular fluid IL-1beta levels.
AB  - BACKGROUND: The study of occlusal therapy in humans with periodontitis is
      problematic due to potential irreversible bone loss in control subjects. The
      hypothesis of this pilot investigation was that increased interocclusal contact
      initiated by short-term occlusal splint disuse would increase tooth mobility and
      the bone-resorptive cytokine interleukin (IL)-1beta in gingival crevicular fluid
      (GCF), comparable to IL-1-positive genotype and increased periodontitis severity.
      METHODS: Nineteen non-smoking chronic periodontitis patients using nocturnal
      occlusal splints and undergoing periodontal maintenance in a private practice
      were evaluated at five time points: 24 hours after continuous splint use; 1, 2,
      and 3 days after no occlusal splint use; and 14 days after resumption of
      customary nighttime splint use. Subjects were evaluated to confirm that the
      plaque index and gingival index were < or = 1.0, and to categorize past
      periodontitis (moderate or severe) and IL-1 genotype (1A +4845 plus IL-1B +3954).
      Test sites on two anterior teeth vulnerable to occlusal trauma were sampled for
      mobility, GCF IL-1beta, and IL-1 receptor antagonist (ra). RESULTS: Tooth
      mobility remained low during the 3-day period when patients were not wearing
      their occlusal appliance. GCF IL-1beta decreased after not wearing the appliances
      (P = 0.016), especially at 48 hours. At this time, genotype-positive subjects had
      higher levels of GCF IL-1beta/IL-1ra than genotype-negative subjects (P = 0.045),
      and patients who had experienced severe periodontitis had higher IL-1beta levels
      than moderate periodontitis subjects (P = 0.004). CONCLUSIONS: These findings
      suggest that short-term discontinuation of occlusal splint therapy in non-smoking
      periodontitis patients undergoing periodontal maintenance does not result in
      potential signs of early occlusal trauma (increasing mobility or GCF IL-1beta).
      Longer-term studies may be needed to determine appropriate therapy applications
      for periodontitis-susceptible patients with definable occlusal discrepancies
      and/or parafunction.

PMID- 14584863
TI  - Effect of loading on the vibration characteristics of thin magnetostrictive
      ultrasonic scaler inserts.
AB  - BACKGROUND: The ultrasonic scaler market has seen an increase in availability of
      thin inserts for periodontal pocket access. While such thin inserts may have
      advantages in negotiating the periodontal pocket, the relatively narrow structure
      may be prone to damping under load. The purpose of this study was to assess the
      vibration characteristics under load of thin, straight, ultrasonic scaler
      inserts. METHODS: Five types of thin inserts were each obtained from three
      manufacturers and were operated using an ultrasonic generator at medium power and
      low water. The displacement amplitude of the scaling tip was measured via a
      scanning laser vibrometer (SLV). Increasing forces up to 1.0 N were applied
      either to the base of the tip (up through its center) or while it was loaded from
      the side. Displacement measurements were obtained using the SLV under these
      loading conditions. RESULTS: Under loading, there was a drop in displacement
      amplitude of all tips. Furthermore, loading of the tips resulted in large
      variations of displacement amplitudes recorded. The mean tip displacements
      recorded ranged from 10 to 30 microm when unloaded and 7 to 25 microm when
      loaded. The fundamental frequency of the ultrasonic tips' oscillation was at 30
      kHz. However, loading resulted in the production of additional subharmonic
      frequencies in the region of 6 to 10 kHz. CONCLUSIONS: Thin ultrasonic scaler
      tips are susceptible to loading. This results in a reduction in the displacement
      amplitude that shows variation not only between tips of different design but also
      between those of the same design made by the same manufacturer. Clinicians and
      researchers should be aware of this variability, which may influence both
      clinical procedures and future research with thin ultrasonic scaling tips.

PMID- 14584865
TI  - Platelet-derived growth factor-BB stimulated cell migration mediated through p38
      signal transduction pathway in periodontal cells.
AB  - BACKGROUND: Intracellular signaling pathways mediate specific responses to growth
      factors. The manipulation of these pathways ultimately may be used to control the
      clinical outcomes of periodontal regenerative therapy. The purpose of this study
      was to examine the role of the p38 signal transduction pathway in the responses
      of periodontal cells to platelet-derived growth factor-BB (PDGF). METHODS:
      Primary cultures of human periodontal ligament cells (PDLs) and gingival
      fibroblasts (GFs) were used for all experiments. Cell numbers, 3H-thymidine
      incorporation, and Boyden chamber assays were used to characterize the effects of
      SB 203580 (SB), a specific inhibitor of the p38 signaling pathway, on cell
      proliferation and migration. An in vitro wound model also was used to assess the
      effects of SB. For the in vitro wound assay, triplicate wells were incubated for
      1, 3, 5, and 7 days using 0.1% fetal bovine serum (FBS), 10% FBS +/- 10 microM
      SB, or 20 ng/ml PDGF +/- 10 microM SB. Digital histomorphometric analysis
      assessed cellular fill within the wound area. RESULTS: SB specifically inhibited
      PDGF-induced migration in the Boyden chamber assays without affecting cell
      proliferation. The wound model data showed similar levels of wound fill for PDLs
      and GFs in 10% FBS. Relative to 10% FBS, PDLs stimulated with PDGF showed
      significantly (P < 0.01, analysis of variance) greater wound fill (74%) than GFs
      (12%). SB inhibited the PDGF-induced wound fill of PDLs and GFs by 64% and 57%,
      respectively. This inhibition was significant (P < 0.01, ANOVA) only for PDLs.
      The addition of SB to 10% FBS did not significantly affect the wound fill
      response of either cell type compared to 10% FBS alone. CONCLUSIONS: These
      results demonstrate that periodontal cells possess distinct responses to PDGF
      that may be altered at the signal transduction level. The manipulation of these
      responses through the use of inhibitors to specific signaling pathways may
      enhance our control of periodontal regeneration in the future.

PMID- 14584864
TI  - Modulation of Porphyromonas gingivalis proteinase activity by suboptimal doses of
      antimicrobial agents.
AB  - BACKGROUND: Antimicrobial agents are sometimes used as adjuncts for the treatment
      of aggressive and refractory forms of periodontitis. In this study, we used a
      culture plate assay to investigate the effect of suboptimal doses of
      antimicrobial agents on proteinase activity of Porphyromonas gingivalis. METHODS:
      A culture plate assay using gelatin as the substrate, which allows a
      semiquantitative determination of proteinase activity, was developed. Suboptimal
      inhibitory concentrations of tetracycline, minocycline, doxycycline,
      metronidazole, penicillin G, or chlorhexidine were added to the medium, and
      proteolysis zones were determined following the growth of three strains of P.
      gingivalis. The effect of antimicrobials on outer membrane vesicle-associated
      gingipains also was determined. RESULTS: The gelatin plate assay was a
      convenient, simple procedure for investigating the effect of suboptimal
      inhibitory concentrations of antimicrobial agents on proteinases produced by P.
      gingivalis. The largest reduction (> 75%) in the proteolysis zones produced by
      three strains of P. gingivalis was obtained with minocycline. Tetracycline and
      doxycycline also reduced the proteolysis zones. A suboptimal inhibitory
      concentration of chlorhexidine increased the proteolysis zones by up to 70%.
      Metronidazole and penicillin G produced no noticeable effect. The suboptimal
      inhibitory concentrations of minocycline, tetracycline, and doxycyline did not
      reduce the activity of outer membrane vesicle-associated Arg- and Lys-gingipains.
      CONCLUSION: Results from this study suggest that sublethal concentrations of some
      antimicrobial agents in subgingival sites have the potential to affect the
      physiology of P. gingivalis, notably by increasing or decreasing the proteolytic
      activity of the bacteria.

PMID- 14584866
TI  - Distribution of periodontal pathogens in Korean aggressive periodontitis.
AB  - BACKGROUND: Microbial associations in aggressive periodontitis versus different
      ethnic origins are substantially unknown. We undertook this study to determine
      the prevalence of seven putative periodontopathogens in Korean patients and to
      evaluate microbial differences in localized and generalized aggressive
      periodontitis patients. METHODS: Thirty-nine aggressive periodontitis patients
      between 20 and 35 years old (24 males and 15 females; mean age 29.6 years) were
      selected according to clinical criteria. The patients were subclassified into 17
      localized and 22 generalized aggressive periodontitis patients. In each of the 39
      individuals, subgingival plaque samples were collected from four diseased teeth
      (> or = 6 mm probing depth, 156 sites) and one healthy site (< or = 3 mm probing
      depth, 39 sites). Polymerase chain reaction (PCR) of the 16S ribosomal RNA gene
      fragments (about 530 bp) of plaque bacteria and their subsequent detection by dot
      blot hybridization using specific oligonucleotide probes were performed to
      determine the presence of seven periodontopathogens. RESULTS: The prevalences
      were 75% for Actinobacillus actinomycetemcomitans, 94.2% for Tannerella
      forsythensis (formerly Bacteroides forsythus), 99.4% for Fusobacterium sp., 85.9%
      for Micromonas micros (formerly Peptostreptococcus micros), 96.8% for
      Porphyromonas gingivalis, 78.8% for Prevotella intermedia, and 96.8% for
      Treponema sp. The prevalences of these bacteria were significantly higher in
      diseased sites than in healthy sites. Logistic regression analysis showed that P.
      intermedia was more significantly associated with generalized aggressive
      periodontitis than the localized form, with an odds ratio of 3.28 (95% confidence
      interval 1.26-8.56, P = 0.015). CONCLUSIONS: Our results demonstrate that the
      seven periodontal pathogens analyzed are strongly associated with Korean
      aggressive periodontitis. In particular, P. intermedia are more significantly
      associated with generalized aggressive periodontitis, a more severe and
      progressive form, than with localized aggressive periodontitis.

PMID- 14584867
TI  - Periodontal disease in HIV-positive individuals: association of periodontal
      indices with stages of HIV disease.
AB  - BACKGROUND: Periodontal disease has been previously associated with human
      immunodeficiency virus (HIV) infection, and HIV infection has been considered a
      modifier of periodontal disease. The aim of this study was to report the
      prevalence and severity of periodontal disease in a population of HIV-positive
      individuals and to investigate the association between clinical periodontal
      indices and the stage of HIV disease, as expressed by CD4 cell counts. METHODS:
      Thirty-nine male HIV-positive patients were recruited and a medical history was
      taken. To evaluate periodontal disease, probing depth (PD), attachment level loss
      (AL), bleeding index (BI), and modified gingival index (MGI) were recorded.
      Associations between the above indices and CD4 counts were examined. RESULTS:
      Immunocompromised patients (with CD4 cell counts < 200 cells/microl) showed
      significantly lower BI and fewer sites with PD and AL > 4 mm compared to patients
      with CD4 cell counts > 200 cells/microl. When patients with CD4 counts < 500
      cells/microl were considered alone, a correlation was observed between CD4 cell
      counts and BI (r2 = 0.1617, P = 0.0463), MGI (r2 = 0.2123, P = 0.0204), and
      number of sites with AL > 4 mm (r2 = 0.1469, P = 0.056). CONCLUSIONS: Severely
      immunocompromised HIV-positive patients showed less severe gingival inflammation
      than expected. Patients with CD4 cell counts > 500 cells/microl showed no
      association between CD4 cell count and periodontal indices.

PMID- 14584868
TI  - Digital image analysis of cadaver mandibular trabecular bone patterns.
AB  - BACKGROUND: The purpose of this study was to investigate the source of
      radiographic trabecular patterns by removing trabecular bone in four sequential
      steps from six cadaver mandible sections, radiographing the sections after each
      removal, and using four digital-image analysis methods to quantify any resulting
      changes to the radiographs. METHODS: Mandible sections were cut sagittally into
      halves. Trabecular bone was removed from each section in four stages. Following
      each stage, standardized radiographs were taken, using direct digital equipment.
      Trabecular bone in the resulting digital images was measured with four methods.
      Mean gray level values (method 1) and cumulative percent histograms (method 2)
      were calculated from the raw data. Morphological image processing was used to
      skeletonize the trabecular structure, which was quantified by counting the number
      of trabecular ends and segments in the skeletonized images (method 3) and
      performing fractal analyses of the skeletonized images (method 4). Repeated
      measures analysis of variance (ANOVA) was used to test for changes in
      measurements attributable to bone removal. RESULTS: Repeated measures ANOVA
      indicated that the use of gray levels, cumulative percent histograms, and
      morphologic operators resulted in highly significant changes in measurements
      following bone removal (P < 0.01). Ends and segments demonstrated similar
      performance, with changes highly significant over time (P < 0.01). Fractal
      analysis also resulted in highly significant changes over time (P < 0.01).
      CONCLUSIONS: The analyses performed in this study demonstrated consistent image
      differences following the four steps of bone removal. These differences appeared
      whether light, cancellous bone or heavier endosteal bone was removed. These
      findings indicate that trabecular and endosteal bone combine to form the
      structure that most dentists identify as trabeculae on intraoral radiographs.

PMID- 14584869
TI  - A histopathological investigation on the effect of systemic administration of the
      bisphosphonate alendronate on resorptive phase following mucoperiosteal flap
      surgery in the rat mandible.
AB  - BACKGROUND: The present study was designed to assess histopathologically whether
      the systemic administration of aminobisphosphonate (alendronate), 0.5 mg/kg body
      weight, is effective in preventing alveolar bone resorption following
      mucoperiosteal flap surgery, and whether alendronate modulates tissue factors.
      METHODS: The effect of alendronate on bone resorption was evaluated in
      mucoperiosteal flaps used as a resorptive model. The animals were given
      subcutaneous injections of either saline (control group) or 0.5 mg/kg of
      alendronate (experimental group). The alendronate or saline was administered
      subcutaneously 1 week prior to surgery, immediately prior to surgery, and 1 week
      after surgery. The parameters determined with a semiquantitative subjective
      method for histopathological evaluation were as follows: inflammatory cell
      infiltration (ICI) of adjacent periodontal tissue, degree of fibrosis and
      collagen bundle formation, number and morphology of osteoclasts of the alveolar
      bone and interdental septum, resorption lacunae (osteoclast surfaces), and
      osteoblastic activity (forming surfaces). RESULTS: There were no statistically
      significant differences between the saline and alendronate groups with regard to
      inflammatory cell infiltration, number of osteoclasts, and osteoblastic activity.
      Fibrosis and collagen bundle formation, osteoclast morphologies, and resorption
      lacunae formation were significantly different between the two groups, in favor
      of the alendronate group. CONCLUSIONS: The systemic administration of 0.5 mg/kg
      alendronate was effective in preventing alveolar bone loss and in modulating
      tissue factors. These findings indicate that alendronate would be a valuable
      addition to the therapeutic armamentarium available for the treatment of
      periodontal diseases, either alone or in combination with regenerative components
      such as anti-inflammatory drugs, bone graft materials, and guided tissue
      regeneration techniques, and even with dental implants.

PMID- 14584870
TI  - Relationship between transmission of Porphyromonas gingivalis and fimA type in
      spouses.
AB  - BACKGROUND: Porphyromonas gingivalis is one of the major microbial pathogens
      associated with chronic periodontitis. To eradicate such pathogens by periodontal
      therapy, it is essential to clarify the source of infection. Recent findings
      suggest that the genotype of the fimbriae is one of the important factors in
      infection by P. gingivalis. The objectives of the present study were to
      investigate the transmission of P. gingivalis between spouses and to determine
      the relationship between P. gingivalis fimA type and colonization. METHODS: A
      total of 14 couples were selected to investigate the transmission of P.
      gingivalis and its association with the fimA types. To examine the distribution
      of fimA type in the general population, 32 subgingival plaque samples from 47
      patients with periodontitis were also tested. The transmission of P. gingivalis
      strains was determined by using pulsed field gel electrophoresis (PFGE). P.
      gingivalis strains isolated from the couples and subgingival dental plaque
      samples were studied for fimA classification. RESULTS: The PFGE patterns of P.
      gingivalis strains from matched husbands and wives were identical for six of the
      14 couples. In five of these six couples (83.3%), P. gingivalis strains harboring
      the type II fimA gene were present. The proportion of type II fimA in the strains
      isolated from couples with probable intrafamilial transmission was significantly
      higher than that in patients with periodontitis or in the group of samples
      isolated from one member of a couple. CONCLUSION: This study suggests that fimA
      type II, even though widely distributed in patients with periodontitis, may be an
      important factor in the transmission of P. gingivalis between spouses.

PMID- 14584872
TI  - Adhesion and growth of cultured human gingival fibroblasts on periodontally
      involved root surfaces treated by Er:YAG laser.
AB  - BACKGROUND: The application of Er:YAG laser irradiation, approved in 1997 to be
      used on dental hard tissues, has been investigated for periodontal therapy. The
      aim of this study was to analyze the biocompatibility of root surfaces treated by
      Er:YAG laser. METHODS: Adhesion and growth of cultured human gingival fibroblasts
      on root surfaces treated by either irradiation with Er:YAG laser or curet were
      compared. Thirty single-rooted teeth extracted because of periodontal disease
      were used. Calculus deposits on all experimental surfaces were removed, and the
      teeth were divided into three groups according to the applied treatment: group A,
      root planing with Gracey curet no. 3/4; group B, two irradiations with laser (60
      mJ/pulse, 10 Hz; 10" each with 10-second interval, 3 J/cm2); group C, two
      irradiations with laser (100 mJ/pulse, 10 Hz; 10" each with 10-second interval, 5
      J/cm2). Fragments (5 mm x 6 mm) were obtained from the experimental surfaces.
      Then, 1 x 10(3) cells were seeded on the top of each fragment. One, 2, and 3 days
      after seeding the specimens were prepared for scanning electron microscopy
      analysis, and the cells on the electronmicrographs were counted. The data
      obtained in triplicate were statistically compared by the Kruskall-Wallis test
      complemented by the Dunn test (P < or = 0.05). RESULTS: Human gingival
      fibroblasts adhered to and grew on all treated surfaces. Group B presented a
      significantly higher cell count than did the other two groups at days 1 and 2.
      Three days after seeding the cultured fibroblasts of groups A and B reached total
      confluence. The cell count of group B was significantly higher than that of group
      C. CONCLUSION: The surfaces treated with 60 mJ/pulse Er:YAG laser irradiation
      promoted faster adhesion and growth than surfaces treated with either root
      planing or 100 mJ/pulse Er:YAG laser irradiation.

PMID- 14584871
TI  - Effect of non-surgical periodontal therapy on glycemic control in patients with
      type 2 diabetes mellitus.
AB  - BACKGROUND: The literature suggests that an alteration in glucose metabolism
      occurs as a result of antibacterial periodontal therapy. The objective of this
      study was to monitor the effect of non-surgical periodontal therapy on glycemic
      control in patients with type 2 diabetes mellitus (DM). METHODS: Thirty type 2 DM
      subjects with periodontitis were randomly divided into two groups. Group 1 (G1),
      15 subjects, received one-stage full-mouth scaling and root planing (FMSRP) plus
      amoxicillin/clavulanic acid 875 mg; group 2 (G2), 15 patients, received only
      FMSRP. At baseline and after 3 months, the glycated hemoglobin (HbA1c) values,
      fasting glucose, and clinical parameters (with computerized probing and
      individualized acrylic stents) were recorded. Following therapy, the subjects
      were enrolled in a 2-week interval maintenance program for 3 months. RESULTS:
      After treatment, both groups showed clinical improvements. A probing depth (PD)
      reduction of 0.8 +/- 0.6 mm (P < 0.05) occurred in G1 and 0.9 +/- 0.4 mm in G2 (P
      < 0.05), but there were no significant changes in attachment level. Treatment
      reduced the HbA1c values after the 3-month observation period in both groups;
      however, the reduction in HbA1c values for the G2 group was statistically
      significant, but not for the G1 group. The changes in fasting glucose levels were
      not significant for either group. CONCLUSIONS: Periodontal therapy improved
      glycemic control in patients with type 2 DM in both groups; however, the
      reduction in HbA1c values reached statistical significance only in the group
      receiving scaling and root planing alone [correction].

PMID- 14584873
TI  - A gingival cul-de-sac following a root coverage procedure with a subepithelial
      connective tissue submerged graft.
AB  - BACKGROUND: The subepithelial connective tissue graft (SCTG) used as a submerged
      graft in combination with a partial thickness advanced flap or rotated flap is a
      predictable technique for achieving coverage of the denuded root surface and/or
      for increasing the width of attached gingiva in Miller's class I and II marginal
      tissue recessions. However, even with a successful result, complications may
      occasionally occur. METHODS: A 4-mm marginal tissue recession with an
      insufficient zone of attached gingiva on the facial aspect of a mandibular left
      lateral incisor (#23) was covered with a submerged SCTG and an envelope partial
      thickness flap. The mucogingival defect was successfully corrected. Nevertheless,
      the facial gingiva, specifically between teeth #22 (mandibular left canine) and
      #23, remained bulky and was reshaped 6 months postoperatively. A 5-mm long
      gingival cul-de-sac with an intermittent thick white discharge was detected 3
      months following the gingivoplasty procedure. RESULTS: With a periodontal probe
      kept in the tract, the lining of the cul-de-sac was exposed to the oral cavity by
      making an incision on the facial gingiva, along the axis of the probe, through to
      the lumen. The gingival tissue was then removed with a rotary bur until only a
      thin layer of periosteum remained. The mucosal defect was subsequently repaired
      by grafting with a non-submerged SCTG. The gingival contour was significantly
      improved and no sign of recurrence was noted up to 4 years later. CONCLUSIONS:
      The existence of a cyst cannot be verified without a histological evaluation.
      However, the development of a gingival cyst should be suspected with persistent
      tissue bulkiness and/or emergence of a thick white discharge from a site where a
      submerged SCTG procedure was performed. In addition, the ill-circumscribed border
      around the lesion makes complete elimination of the pathosis relatively hard to
      achieve by a "superficial" gingivoplasty procedure.

PMID- 14584874
TI  - Peripheral giant cell granuloma associated with dental implants.
AB  - BACKGROUND: Peripheral giant cell granuloma (PGCG) is a well-circumscribed lesion
      confined to the alveolar and gingival mucosa. PGCG is considered a reactive
      lesion caused by local irritation or trauma. The objectives of the present study
      were to evaluate the incidence of PGCG in peri-implant lesions submitted for
      histologic examination, to establish its correlation with implant failure, and to
      discuss its pathogenesis. METHODS: The study was conducted on 25 periimplant
      biopsy specimens submitted for histological examination between 1999 and 2001.
      Sections (5 microm) of paraffin embedded tissues were cut and stained with
      hematoxylin and eosin. RESULTS: From the 25 specimens, three (two males and one
      female, ranging in age from 31 to 69 years) were identified as peripheral giant
      cell granuloma. The posterior mandible was affected in two cases and the anterior
      maxilla in one. The clinical appearance was an exophytic mass with a bleeding
      surface. The time interval between implantation and lesion development was from
      several months to 6 years. Recurrence following curettage was found in all cases.
      The implants were stable; however, two were removed either because of bone loss
      around the implant or because of several recurrences. In all cases healing was
      uneventful. CONCLUSIONS: Peripheral giant cell granuloma can develop in
      association with dental implants. Clinically, the lesions are similar to the
      classical PGCG. In the present study, the precise incidence could not be
      concluded because of the small number of selected cases. Due to the aggressive
      nature of the lesion and the high recurrence rate, implants can fail unless the
      lesion is detected early and proper surgical removal is performed. Tissue removed
      from the peri-implant area should always be submitted for histologic examination
      for accurate diagnosis.

PMID- 14584876
TI  - Re: Periodontal terminology revisited. Weinberg MA, Eskow RN (2003;74:563-565).

PMID- 14584875
TI  - Lichen planus and the vulvovaginal-gingival syndrome.
AB  - Lichen planus is a dermatologic disease that affects both skin and mucosa. Here
      we report five cases of lichen planus that presented as the oral component of the
      vulvovaginal-gingival syndrome. Four of the cases were associated with biopsy
      proven oral lichen planus, and all five patients had oral lesions that clinically
      resembled lichen planus. Three patients were taking medications that are
      associated with lichenoid drug reactions; four patients were postmenopausal; and
      all five patients had desquamative vulvovaginitis. Clinicians may see these
      patients when they show persistent signs and symptoms of oral lichen planus. We
      report five case histories and review the 127 cases found in the literature to
      make the practicing clinician aware of this unusual clinical entity. The
      hepatitis C virus association and drug-induced lichenoid mucositis are topics
      that are addressed. In addition, clarification of the issues surrounding the
      premalignant potential of oral lichen planus is provided with evidence,
      rationale, and data from the literature to support the position that true oral
      lichen planus has no inherent predisposition to become malignant.

PMID- 14584877
TI  - Position paper: periodontal maintenance.
AB  - The purpose of this paper is to provide an overview of the role of periodontal
      maintenance procedures in the treatment of periodontal diseases. Reliance on this
      position paper in patient management will not guarantee a successful outcome, as
      periodontal diseases typically involve complex causes and symptoms. Ultimately,
      decisions regarding the diagnosis, treatment, and management of disease, as well
      as subsequent preventive therapy, must be made by the treating practitioner based
      on specific circumstances presented by the patient.

PMID- 14584878
TI  - Antigen-specific B-lymphocyte activation.
AB  - B lymphocytes comprise a major component of the adaptive mammalian immune system,
      having the exclusive ability to produce and secrete immunoglobulins (Ig) of
      various forms (isotypes). This property alone renders B-cell activation critical
      to immunity, but the fully activated B cell also functions in antigen
      presentation and the production of a variety of cytokines and chemokines. There
      are many signals that must be coordinated to achieve and properly regulate
      antigen-specific B-lymphocyte activation and the development of humoral memory.
      This review seeks to summarize these components, and to highlight recent advances
      in each area that contribute to a greater understanding of the complex processes
      involved in B-cell activation.

PMID- 14584879
TI  - Proteoglycan-induced arthritis: immune regulation, cellular mechanisms, and
      genetics.
AB  - Rheumatoid arthritis is probably the least understood systemic autoimmune
      disease, and it affects approximately 1% of the human population. Several lines
      of evidence indicate that the effector mechanism, which initially attacks small
      joints, is T-cell driven. As a result, an aggressive synovial pannus develops,
      which destroys articular cartilage and bone, leading to massive ankylosis and
      deformities of peripheral joints. The disease has a progressive character, with
      the involvement of more and more joints. Although the target organ is the
      synovial joint, there is no clear evidence that any macromolecule of
      cartilaginous tissues, bone, or synovium, could be a preferential autoantigen.
      There are numerous rodent models that simulate some or many of the clinical,
      immunological, or histopathological features of the disease. Recently, it has
      become a strong working hypothesis that MHC and non-MHC genetic components share
      loci that are common in various autoimmune diseases, and in corresponding animal
      models. The most relevant animal models of rheumatoid arthritis appear to be
      those induced by cartilage matrix components such as type II collagen or
      proteoglycan aggrecan. This review summarizes our current knowledge of cartilage
      proteoglycan (aggrecan)-induced arthritis in mice.

PMID- 14584880
TI  - Intestinal calcium transporter genes are upregulated by estrogens and the
      reproductive cycle through vitamin D receptor-independent mechanisms.
AB  - 1alpha,25(OH)2-vitamin D strongly regulates the expression of the epithelial
      calcium channel CaT1. CaT1 expression is reduced in ERKOalpha mice and induced by
      estrogen treatment, pregnancy, or lactation in VDR WT and KO mice. Estrogens and
      vitamin D are thus independent potent regulators of the expression of this
      calcium influx mechanism, which is involved in active intestinal calcium
      absorption. INTRODUCTION: Active duodenal calcium absorption consists of three
      major steps: calcium influx into, transfer through, and extrusion out of the
      enterocyte. These steps are carried out by the calcium transport protein 1
      (CaT1), calbindin-D9K, and the plasma membrane calcium ATPase (PMCA1b),
      respectively. We investigated whether estrogens or hormonal changes during the
      female reproductive cycle influence the expression of these genes, and if so,
      whether these effects are vitamin D-vitamin D receptor (VDR) dependent. MATERIALS
      AND METHODS: We evaluated duodenal expression patterns in estrogen receptor
      (ER)alpha and -beta knockout (KO) mice, as well as in ovariectomized, estrogen
      treated, pregnant, and lactating VDR wild-type (WT) and VDR KO mice. RESULTS:
      Expression of calcium transporter genes was not altered in ERKObeta mice. CaT1
      mRNA expression was reduced by 55% in ERKOalpha mice, while the two other calcium
      transporter genes were not affected. Ovariectomy caused no change in duodenal
      expression pattern of VDR WT and KO mice, whereas treatment with a pharmacologic
      dose of estrogens induced CaT1 mRNA expression in VDR WT (4-fold) and KO (8-fold)
      mice. Pregnancy enhanced CaTI expression equally in VDR WT and KO mice (12-fold).
      Calbindin-D9K and PMCA1b expression increased to a lesser extent and solely in
      pregnant VDR WT animals. In lactating VDR WT and KO mice, CaT1 mRNA expression
      increased 13 times, which was associated with a smaller increase in calbindin-D9K
      protein content and PMCA1b mRNA expression. CONCLUSIONS: Estrogens or hormonal
      changes during pregnancy or lactation have distinct, vitamin D-independent
      effects at the genomic level on active duodenal calcium absorption mechanisms,
      mainly through a major upregulation of the calcium influx channel CaT1. The
      estrogen effects seem to be mediated solely by ERalpha.

PMID- 14584881
TI  - Estrogen, vitamin D, and calcium transport.

PMID- 14584883
TI  - Three novel mutations in SQSTM1 identified in familial Paget's disease of bone.
AB  - Mutations in Sequestosome 1 (SQSTM1) have been shown to segregate with familial
      Paget's disease of bone (PDB). We examined the coding sequence of SQSTM1 in five
      PDB pedigrees and found three novel mutations clustered around the C-terminal
      ubiquitin associated domain. Disruptions of the C-terminal domain of SQSTM1 seem
      to be a leading cause of familial PDB. INTRODUCTION: The characteristic features
      of Paget's disease of bone (PDB) are caused by focal areas of excessive and
      uncoordinated bone remodeling. A total of seven genetic loci (PDB1-PDB7) have
      been reported to be associated with the disease. The gene for Sequestosome 1
      (p62; SQSTM1) has been identified as the causative gene for PDB3 in numerous
      French-Canadian families and families predominantly of British descent. To date,
      a total of three mutations, all affecting the ubiquitin-associated domain of
      SQSTM1, have been identified: a single 1215 C to T (P392L) transversion in exon
      8, a T insertion in exon 8 (E396X), and a G to A mutation at the splice junction
      of exon 7 (IVS7 + 1). MATERIALS AND METHODS: DNA was isolated from blood
      collected from the members of five U.S. PDB pedigrees. Mutation analysis of the
      coding sequence of the SQSTM1 gene was performed on the proband and other key
      individuals in the pedigrees. RESULTS: Four of the five families had SQSTM1
      mutations. Three of these mutations were novel: a single base deletion in exon 8
      at position 1210 (1210delT) resulting in a premature stop codon at amino acid
      394, a single C deletion in exon 8 at position 1215 (1215delC) also resulting in
      a premature stop codon at amino acid 394, and a single 1200 C to T (P387L)
      transversion in exon 7. CONCLUSION: Noteworthy is the fact that these three
      SQSTM1 mutations, in addition to the three previously described mutations, are
      clustered near the C-terminal of the protein. These mutations may be acting in a
      dominant-negative fashion to disrupt the ubiquitin-binding function, which could
      result in abnormal activation of the NF-kappaB pathway and the subsequent
      activation of the osteoclasts. These findings imply that SQSTM1 mutations may
      play a role in the majority of familial PDB in the United States.

PMID- 14584882
TI  - Chloride channel ClCN7 mutations are responsible for severe recessive, dominant,
      and intermediate osteopetrosis.
AB  - Among 94 osteopetrotic patients presenting with a severe clinical picture and
      diagnosed early in life, 12 bore mutations in the ClCN7 gene, but only 7 of them
      had the expected two recessive mutations. The remaining five patients seem to be
      heterozygous for a ClCN7 mutation, and significant variations were observed in
      the clinical manifestations of their disease, even within the same family.
      INTRODUCTION: Human osteopetroses are a heterogeneous group of diseases that
      include both infantile severe, autosomal recessive (ARO) and adult autosomal
      dominant (ADO) forms. Two genes, Atp6a3 (TCIRG1) and ClCN7, have been shown to be
      associated with human ARO, the latter of which is also thought to be responsible
      for ADO-II. However, patients with an intermediate phenotype have been described:
      the genetic basis of these observances is unknown. MATERIALS AND METHODS: In this
      study, we report the clinical and molecular analysis of 94 patients in which a
      diagnosis of severe osteopetrosis was made within the first 2 years of age. Both
      TCIRG1 and CLCN7 genes were sequenced in all patients and the molecular findings
      were correlated to clinical parameters. RESULTS AND CONCLUSIONS: In 56 of 94
      patients with a classical picture of ARO, TCIRG1-dependent recessive mutations
      were found. In contrast, ClCN7 mutations were found in 12 cases (13%) of severe
      osteopetrosis, but only 7 of them had two recessive mutations identified: in 6 of
      these 7 cases, central nervous system manifestations were noted, and these
      patients had a poor prognosis. The remaining five cases were heterozygous for a
      ClCN7 mutation, including two brothers from a large family with a history of ADO
      II in which the presence of a second ClCN7 mutation was formally excluded.
      Despite an early and severe clinical presentation, these five patients all
      reached adulthood, suggesting that the degree of dominant interference with
      chloride channel function can vary widely. Our findings suggest that recessive
      ClCN7-dependent ARO may be associated with CNS involvement and have a very poor
      prognosis, whereas heterozygous ClCN7 mutations cause a wide range of phenotypes
      even in the same family, ranging from early severe to nearly asymptomatic forms.
      These findings have prognostic implications, might complicate prenatal diagnosis
      of human osteopetroses, and could be relevant to the management of these
      patients.

PMID- 14584884
TI  - A single nucleotide polymorphism under the reverse primer binding site may lead
      to BsmI mis-genotyping in the vitamin D receptor gene.
AB  - The BsmI polymorphism in the VDR gene has been extensively investigated by PCR
      and restriction digestion in bone genetics. A SNP within the corresponding region
      for the previously published reverse primer was observed and confirmed by DNA
      sequencing. BsmI mis-genotyping caused by this SNP could confound genetic
      findings. INTRODUCTION: By analyzing the FokI, BsmI, ApaI, and TaqI polymorphisms
      in the vitamin D receptor (VDR) gene, we observed a significantly different
      genotype distribution in the BsmI polymorphic locus with a deviation from Hardy
      Weinberg equilibrium. One of the reasons for polymerase chain reaction (PCR) non
      amplification may be a mismatched base at the primer binding region. Therefore,
      the aim of this study was to analyse whether a single nucleotide polymorphism
      (SNP), which has been recently described as TruI, is responsible for the
      discrepancy between expected and observed genotype frequencies. MATERIALS AND
      METHODS: The VDR genotypes were identified in a cohort of 165 peri- and
      postmenopausal women of white origin. PCR amplification was carried out using the
      originally published primers and followed by restriction cleavage. The BsmI
      genotypes were further verified with a reverse primer external to the original
      binding site. The presence of the TruI polymorphism under the previously
      published reverse primer was confirmed by a restriction digestion and DNA
      sequencing. In Bb subjects, the colocalization of b allele with the TruI
      restriction site on the same chromosome was confirmed by a simultaneous digestion
      of the PCR product with both BsmI and TruI restriction enzymes. RESULTS: The BsmI
      reanalysis with an external primer provided a higher number of heterozygous
      subjects with a proportionally smaller number of BB subjects, and the changed
      genotype distribution was under Hardy-Weinberg equilibrium (BB, 31; Bb, 80; bb,
      54; r = 0.0203; p = 0.90). In our primary analysis, the presence of the TruI
      polymorphism led to a drop out of b allele during PCR amplification and thus to
      the false prevalence of BB genotypes (BB, 50; Bb, 61; bb, 54; r = 11.17; p =
      0.01). CONCLUSION: The SNP in the region corresponding to the reverse primer may
      lead to BsmI mis-genotyping, which may have confounded some previous genetic
      studies.

PMID- 14584885
TI  - Genetic effects for femoral biomechanics, structure, and density in C57BL/6J and
      C3H/HeJ inbred mouse strains.
AB  - Genome-wide QTL analysis for bone density, structure, and biomechanical
      phenotypes was performed in 999 (B6xC3H)F2 mice. Multivariate phenotypes were
      also derived to test for pleiotropic QTL effects. Highly significant QTLs were
      detected with pleiotropic effects on many of these phenotypes, and QTLs with
      unique effects on specific phenotypes were found as well. INTRODUCTION: The
      inbred C57BL/6J (B6) and C3H/HeJ (C3H) mouse strains were previously shown to
      segregate quantitative trait loci (QTLs) for femoral bone density. MATERIALS AND
      METHODS: The 999 s filial (F2) mouse progeny were further phenotyped for measures
      of femoral biomechanics (load to failure, Fu; work to failure, U; stiffness, S),
      structure (polar moment of inertia, Ip; moment of inertia ratio, Ir), and more
      specific femoral midshaft bone density measures (cortical and total vBMD). Two
      novel multivariate phenotypes were computed using principal component analysis,
      thus aiding in the exploration of pleiotropic effects of the QTLs detected.
      RESULTS AND CONCLUSIONS: Results of a genome-wide analysis provided strong
      evidence of pleiotropic QTL effects on chromosome 4, with six of the seven
      primary phenotypic measures, representing femoral biomechanics, density, and
      structure, producing LOD scores greater than 8. Chromosomes 1, 8, 13, and 14 were
      also identified as harboring QTLs that affect phenotypes in two of the three
      aspects of bone properties. QTLs uniquely contributing to variability in
      biomechanical measures were identified on chromosomes 10 and 12, whereas a QTL
      solely affecting structure was found on chromosome 17. Analysis of the evidence
      for pleiotropic effects using principal component analysis revealed pleiotropic
      QTLs on chromosomes 4 and 14, influencing nearly all the bone phenotypes measured
      and revealed QTLs on chromosomes 1, 8, 13, and 17 with pleiotropic effects
      restricted to either density or the structure and stiffness phenotypes. The use
      of multivariate phenotypes has allowed us to identify pleiotropic effects of
      several QTLs previously linked in studies of other mouse strains and in human
      studies of bone mineral density and femoral structure, which will provide
      important insight regarding the importance of allelic variation on the entire
      skeleton.

PMID- 14584886
TI  - Structural and biomechanical basis of sexual dimorphism in femoral neck fragility
      has its origins in growth and aging.
AB  - The structural basis for sex differences in femoral neck (FN) fragility was
      studied in 1196 subjects and 307 patients with hip fracture. The absolute and
      relative patterns of modeling and remodeling on the periosteal and endocortical
      envelopes during growth and aging produce changes in FN geometry and structure
      that results in FN fragility in both sexes and sexual dimorphism in hip fracture
      risk in old age. INTRODUCTION: Femoral neck (FN) fragility in old age is usually
      attributed to age-related bone loss, while the sex differences in hip fracture
      rate are attributed to less bone loss in men than in women. The purpose of this
      study was to define the structural and biomechanical basis underlying the
      increase in FN fragility in elderly men and women and the structural basis of sex
      differences in hip fracture incidence in old age. MATERIALS AND METHODS: We
      measured FN dimensions and areal bone mineral density in 1196 healthy subjects
      (801 females) 18-92 years of age and 307 patients (180 females) with hip fracture
      using DXA. We then used the DXA-derived FN areal bone mineral density (BMD) and
      measured periosteal diameter to estimate endocortical diameter, cortical
      thickness, section modulus (a measure of bending strength), and buckling ratio
      (indices for structural stability). RESULTS: Neither FN cortical thickness nor
      volumetric density differed in young adult women and men after height and weight
      adjustment. The sex differences in geometry were confined to the further
      displacement of the cortex from the FN neutral axis in young men, which produced
      13.4% greater bending strength than in young women. Aging amplified this
      geometric difference; widening of the periosteal and endocortical diameters
      continued in both sexes but was greater in men, shifting the cortex even further
      from the neutral axis maintaining bending strength in men, not in women. In both
      sexes, less age-related periosteal than endocortical widening produced cortical
      thinning increasing the risk for structural failure by local buckling of the
      enlarged thin walled FN. Relative to age-matched controls, women and men with hip
      fractures had reduced cortical thickness, but FN periosteal diameter was
      increased in women and reduced in men, differences are likely to be originated in
      growth. CONCLUSIONS: The absolute and relative patterns of modeling and
      remodeling on the periosteal and endocortical envelopes during growth and aging
      produce changes in FN diameters, cortical thickness, and geometry that results in
      FN fragility in both sexes and sexual dimorphism in hip fracture risk in old age.

PMID- 14584887
TI  - Bone remodeling at the endocortical surface of the human femoral neck: a
      mechanism for regional cortical thinning in cases of hip fracture.
AB  - Endocortical remodeling and wall thickness (W.Th.) were measured in femoral neck
      bone from 12 female fracture cases (81.3 +/- 1.5 years) and 12 sex-matched
      controls (81.9 +/- 1.9 years). Regionally, osteoid and eroded surface were
      increased, whereas W.Th. was reduced. These processes likely contribute to
      cortical bone loss seen in hip fracture. INTRODUCTION: Because periosteal
      expression of alkaline phosphatase was similar between cases and controls, we
      hypothesized that the mechanism causing the marked femoral neck cortical thinning
      associated with hip fracture may be net endocortical bone loss. METHODS: Twelve
      female cases of femoral neck fracture (mean age = 81.3 +/- 1.5 years) and 12 age-
      and sex-matched postmortem controls (mean age = 81.9 +/- 1.9 years) were included
      in the study. Samples of their femoral neck bone were embedded in methyl
      methacrylate, sectioned at 10 microm, and stained with Solochrome cyanine R and
      Goldner's trichrome for the detection of osteoid (%OS/BS) and resorption surfaces
      (%ES/BS) respectively. In addition, wall thickness (W.Th.) and lamellar thickness
      (Lm.Th.) data were also collected from identifiable endocortical bone packets as
      a measure of formative potential. RESULTS AND CONCLUSIONS: %OS/BS was
      significantly elevated in the anterior (control = 3.4 +/- 0.7: fracture = 11.0 +/
      2.3; p = 0.0001), inferior (3.4 +/- 1.0: 9.9 +/- 3.0; p = 0.0009), and posterior
      quadrants (3.2 +/- 0.8: 9.1 +/- 2.3; p = 0.0021). Only for anterior region was
      increased %ES/BS demonstrated in the fracture group (2.8 +/- 0.6: 5.3 +/- 0.7; p
      = 0.055). W.Th. (mm) was reduced only in the inferior region of the fracture
      cases (control = 33.7 +/- 1.2: fracture = 30.6 +/- 0.9; p = 0.013), whereas
      Lm.Th. was also reduced inferiorly (control = 2.7 +/- 0.08: fracture = 2.5 +/-
      0.08; p = 0.042). These data suggest that an endocortical remodeling imbalance
      involving reduced bone formation within inferior region coupled with elevated
      anterior resorption may make an important contribution to the cortical thinning
      observed in cases of femoral neck fracture.

PMID- 14584888
TI  - Trabecular bone tissue strains in the healthy and osteoporotic human femur.
AB  - Quantitative information about bone tissue-level loading is essential for
      understanding bone mechanical behavior. We made microfinite element models of a
      healthy and osteoporotic human femur and found that tissue-level strains in the
      osteoporotic femoral head were 70% higher on average and less uniformly
      distributed than those in the healthy one. INTRODUCTION: Bone tissue stresses and
      strains in healthy load-adapted trabecular architectures should be distributed
      rather evenly, because no bone tissue is expected to be overloaded or unused. In
      this study, we evaluate this paradigm with the use of microfinite element
      (microFE) analyses to calculate tissue-level stresses and strains for the human
      femur. Our objectives were to quantify the strain distribution in the healthy
      femur, to investigate to what extent this distribution is affected by
      osteoporosis, to determine if osteoporotic bone is simply bone adapted to lower
      load levels, and to determine the "safety factor" for trabecular bone. MATERIALS
      AND METHODS: microFE models of a healthy and osteoporotic proximal femur were
      made from microcomputed tomography images. The models consisted of over 96 and 71
      million elements for the healthy and osteoporotic femur, respectively, and
      represented their internal and external morphology in detail. Stresses and
      strains were calculated for each element and their distributions were calculated
      for a volume of interest (VOI) of trabecular bone in the femoral head. RESULTS:
      The average tissue-level principal strain magnitude in the healthy VOI was 304 +/
      185 microstrains and that in the osteoporotic VOI was 520 +/- 355 microstrains.
      Calculated safety factors were 8.6 for the healthy and 4.9 for the osteoporotic
      femurs. After reducing the force applied to the osteoporotic model to 59%, the
      average strain compared with that of the healthy femur, but the SD was larger
      (208 microstrains). CONCLUSIONS: Strain magnitudes in the osteoporotic bone were
      much higher and less uniformly distributed than those in the healthy one. After
      simulated joint-load reduction, strain magnitudes in the osteoporotic femur were
      very similar to those in the healthy one, but their distribution is still wider
      and thus less favorable.

PMID- 14584889
TI  - Long-term variability of markers of bone turnover in postmenopausal women and
      implications for their clinical use: the OFELY study.
AB  - Bone marker variability has raised concern for its use in individual patients.
      Serum osteocalcin (formation) and CTX (resorption) were measured every year for 4
      years in 268 postmenopausal women. Seventy percent to 80% of women classified as
      having high bone turnover at baseline were similarly classified by the same
      methods 4 years later. INTRODUCTION: High bone marker levels are a risk factor
      for osteoporosis in postmenopausal women, but variability of measurements has
      raised doubts about their clinical use in an individual patient. METHODS: We
      studied 268 untreated postmenopausal women (50-81 years of age) belonging to a
      population-based prospective cohort. We collected fasting morning blood samples
      every year for 4 years to measure serum intact osteocalcin (OC) and serum C
      terminal cross-linked telopeptide of type I collagen (CTX) as bone formation and
      resorption markers, respectively. RESULTS: Serum OC and CTX remained stable
      during follow-up (+ 1.2%/year, p = 0.003 and -0.13%/year, p = 0.70 for OC and S
      CTX, respectively). At baseline, women were classified as having low (tertile 1),
      intermediate (tertile 2), or high (tertile 3) bone turnover. Agreement of
      classification between baseline and 4-year measurements was moderate (kappa [95%
      CI]: 0.51 [0.43-0.59] and 0.52 [0.44-0.60] for OC and S-CTX, respectively). Less
      than 10% of women in tertile 1 or 3 of either marker at baseline were found in
      the opposite tertile 4 years later. When the two markers were combined, only 2%
      of women at high turnover at baseline--defined as OC and/or S-CTX in tertile 3-
      were classified at low turnover 4 years later. Among women classified at high
      bone turnover at baseline (tertile 3), 70-80% were also found at high turnover 4
      years later. Among women in tertile 2, only 51% and 43% for OC and CTX,
      respectively, remained in the same tertile at the second measurement.
      CONCLUSIONS: Serum levels of bone formation and resorption markers are stable
      over 4 years in postmenopausal women, on average. The majority of women
      classified as having high bone turnover were similarly classified by the same
      methods 4 years later. However, 20-30% of these women at risk for fracture would
      be incorrectly classified, suggesting that further investigation would be
      required to reduce the number of patients who would be treated unnecessarily if
      the decision was made on bone marker measurement. For women with intermediate
      levels, classification may be improved by a second measurement or by combining
      two markers.

PMID- 14584890
TI  - Association between bone mineral density and the use of nonsteroidal anti
      inflammatory drugs and aspirin: impact of cyclooxygenase selectivity.
AB  - BMD was examined in users of NSAIDs (by COX selectivity) and aspirin in the
      Health ABC cohort (n = 2853). Significantly higher BMD was found in users of
      relative COX-2 selective NSAIDs with aspirin (COX-2/ASA) compared with nonusers.
      This suggests a role for COX-2/ASA in osteoporosis. INTRODUCTION: The purpose of
      this study was to determine the relationship of nonsteroidal anti-inflammatory
      drug (NSAID) use, by cyclo-oxygenase selectivity (COX), and aspirin use on bone
      mineral density (BMD) in participants from the Health, Aging, and Body
      Composition (Health ABC) population-based cohort. It is known that NSAIDs inhibit
      the COX enzyme and decrease production of prostaglandins, which are involved in
      regulation of bone turnover. COX has two isoforms, COX-1 and COX-2. Production of
      prostaglandins associated with bone loss is primarily mediated through the COX-2
      pathway. In addition, aspirin may have effects on bone independent of the
      prostaglandin pathway. MATERIALS AND METHODS: NSAID (by COX selectivity) and
      aspirin use and BMD were assessed in 2853 adults (49.5% women, 50.5% men: 43.1%
      black, 56.9% white; mean age: 73.6 years) from the Health ABC cohort. For the
      purposes of this analysis, relative COX-1 selective NSAIDs were defined as having
      a ratio of COX-1 IC50 to COX-2 IC50 of > 1 in whole blood, and relative COX-2
      selective NSAIDs were defined as having a ratio of COX-1 IC50 to COX-2 IC50 of <
      1 in whole blood. Analysis of covariance was used to compare BMD across each
      NSAID use and aspirin use category adjusting for age, race, gender, weight,
      height, study site, calcium and vitamin D supplementation, Womac score, history
      of rheumatoid arthritis, history of arthritis other than rheumatoid, and smoking
      status. RESULTS: After adjustment for possible confounders, current use of
      relative COX-2 selective NSAIDs with aspirin was associated with higher BMD at
      the whole body (4.2%, 1.2-7.3 CI) and total hip (4.6%, 0.5-8.8 CI) by DXA and at
      both trabecular (34.1%, 15.4-52.7 CI) and cortical spine (12.8%, 2.3-23.3 CI) by
      quantitative computed tomography. CONCLUSIONS: Our data suggest that the
      combination of relative COX-2 selective NSAIDs and aspirin is associated with
      higher BMD at multiple skeletal sites in men and women.

PMID- 14584891
TI  - In vitro acoustic waves propagation in human and bovine cancellous bone.
AB  - The acoustic behavior of cancellous bone with regard to its complex poroelastic
      nature has been investigated. The existence of two longitudinal modes of
      propagation is demonstrated in both bovine and human cancellous bone. Failure to
      take into account the presence of these two waves may result in inaccurate
      material characterization. INTRODUCTION: Acoustic wave propagation is now a
      commonly used nondestructive method for cancellous bone characterization.
      However, wave propagation in this material may be affected by fluid-solid
      interactions inherent to its poroelastic nature, resulting in two different
      longitudinal waves. This phenomenon has been demonstrated in previous studies and
      is in agreement with Biot's theory. The purpose of this paper is to extend these
      findings to human trabecular bone and to thoroughly investigate these two waves.
      MATERIALS AND METHODS: Sixty human and 14 bovine cancellous bone cubic specimens
      were tested in vitro in three different directions using an immersion acoustic
      transmission method. Original procedures were developed to quantify both velocity
      and attenuation characteristics of each wave. In term of attenuation, a modified
      broadband ultrasound attenuation (BUA), describing the rate of change of the
      frequency-dependent attenuation, was defined for each wave (FDUA). RESULTS: Both
      waves were identified in most of the specimens. The fast wave velocities
      demonstrated a negative linear correlation with porosity (1500-2300 m/s, R2 =
      0.44, p < 10(-3)), whereas the slow wave velocities exhibited two different
      behaviors: (1) a first set of data clearly dependent on porosity showing a
      positive linear correlation (1150-1450 m/s, R2 = 0.26, p < 10(-3)) and (2) a
      second group independent on porosity. The fast wave FDUA (20-140 dB/cmMHz) showed
      a parabolic behavior and reached a maximum for 75% porosity (second degree
      relationship R2 = 0.41,p < 10(-3)), whereas a positive linear behavior was
      observed for the slow wave FDUA (15-40 dB/cmMHz; R2 = 0.15, p < 10(-2)).
      CONCLUSIONS: Existence of two wave propagation modes were demonstrated in human
      cancellous bone. Our data suggest that, in some cases, the amplitude of the slow
      wave is much larger than the amplitude of the fast wave. For this reason, care
      should be taken when using measurement systems that incorporate simple threshold
      detection because the fast wave could remain undetected. Moreover, failure to
      consider the presence of these two waves could result in an inaccurate
      quantification of cancellous bone physical properties.

PMID- 14584892
TI  - Extracellular calcium is a potent inducer of cyclo-oxygenase-2 in murine
      osteoblasts through an ERK signaling pathway.
AB  - [Ca2+]e may be important in bone turnover. We found [Ca2+]e induces COX-2
      transcription and PGE2 production in primary calvarial osteoblasts through an ERK
      signaling pathway. Inhibition of PGE2 production inhibited the [Ca2+]e
      stimulation of osteoblastic differentiation but not the increase in cell number.
      Hence, some effects of [Ca2+]e on bone may be mediated by COX-2. INTRODUCTION:
      Local changes in extracellular calcium ([Ca2+]e) may play an important role in
      bone turnover. We examined the possibility that prostaglandins produced by cyclo
      oxygenase-2 (COX-2) could mediate some of the effects of [Ca2+]e on osteoblasts.
      METHODS: We examined the [Ca2+]e induction of COX-2 expression and prostaglandin
      E2 (PGE2) production in primary osteoblasts (POBs) obtained by sequential
      enzymatic digestion of mouse calvariae. We measured mRNA and protein levels by
      Northern and Western analyses and PGE2 production in culture medium by
      radioimmunoassay (RIA). COX-2 promoter activity was measured as luciferase
      activity in calvarial osteoblasts derived from mice transgenic for 371 bp of the
      COX-2 promoter fused to a luciferase reporter gene. RESULTS AND CONCLUSIONS: COX
      2 mRNA and protein expression were induced by 3-40 mM of [Ca2+]e. [Ca2+]e (5 mM)
      induced COX-2 mRNA within 30 minutes; levels peaked at 6-9 h and remained
      elevated at 24 h. Cumulative medium PGE2 was increased at 3 h, with levels rising
      to 30 nM at 24 h. PGE2 production in POBs from mice with only COX-1 gene
      expression was 1/40th of that in POBs from mice with both COX-1 and COX-2 gene
      expression. [Ca2+]e increased alkaline phosphatase activity and osteocalcin mRNA,
      and this increase was blocked by inhibiting PGE2 production. [Ca2+]e stimulation
      of COX-2 promoter activity correlated with the induction of COX-2 mRNA
      expression. [Ca2+]e induced rapid and transient phosphorylation of extracellular
      signal-regulated kinase (ERK) in POBs, which peaked at 5-10 minutes. Inhibition
      of ERK phosphorylation with the specific inhibitors, PD-98059 and U-0126,
      decreased the [Ca2+]e induction of both COX-2 mRNA and luciferase activity by 70
      80%. Although less effective than [Ca2+]e, strontium [Sr2+]e also induced COX-2
      mRNA and promoter activity in POBs through an ERK signaling pathway. We conclude
      that [Ca2+]e is a potent transcriptional inducer of COX-2 expression and PGE2
      production in osteoblasts through an ERK signaling pathway.

PMID- 14584893
TI  - Calcyclin mediates serum response element (SRE) activation by an osteoblastic
      extracellular cation-sensing mechanism.
AB  - The molecular mechanism of sensing extracellular cations in osteoblasts is
      controversial. Using an expression-cloning strategy, the calcium-binding protein
      calcyclin was found to mediate the response of MC3T3-E1 osteoblasts to
      extracellular cations, but not the calcimimetic NPS-568, indicating the presence
      of another cation-sensing mechanism. Further understanding of calcyclin function
      in osteoblasts may identify novel targets for regulating bone formation.
      INTRODUCTION: Extracellular calcium and other cations seem to regulate the
      function of osteoblasts through a distinct calcium-sensing mechanism that is
      coupled to activation of c-fos gene transcription. The identity of this calcium
      sensing mechanism is unknown. METHODS: To identify molecules that participate in
      this extracellular cation-sensing pathway, we developed an expression cloning
      strategy in COS-7 cells using cation stimulation of a serum response element
      (SRE) luciferase reporter derived from the c-fos promoter to screen a mouse MC3T3
      E1 osteoblast cDNA library. RESULTS AND CONCLUSIONS: We identified calcyclin
      (S100A6), a calcium-binding protein of the EF-hand type belonging to the S100
      family, as being responsible for transferring a cation-sensing response from
      osteoblasts to COS-7 cells. Transfection of the calcyclin cDNA into COS-7 and HEK
      293 cells confirmed that the overexpression of calcylin caused these cells to
      gain the ability to sense extracellular cations, including aluminum, gadolinium,
      calcium, and magnesium. Conversely, we found that an antisense calcyclin
      construct reduced calcyclin expression and partially inhibited the cation-sensing
      response in MC3T3-E1 osteoblasts. These results implicate calcyclin in the
      activation of SRE and establish a role for calcyclin as an accessory protein
      involved in the cation-sensing pathway in osteoblasts.

PMID- 14584894
TI  - Perturbations in bone formation and resorption in insulin-like growth factor
      binding protein-3 transgenic mice.
AB  - IGF-I and their binding proteins are important in bone health. Examination of
      BMD, osteoblast proliferation, and markers of bone resorption in transgenic mice
      that constitutively overexpress IGFBP-3 indicates that overexpression of IGFBP-3
      increases osteoclast number and bone resorption, impairs osteoblast
      proliferation, and has a significant negative effect on bone formation.
      INTRODUCTION: Low serum insulin-like growth factor I (IGF-I) levels correlate
      with an increased risk of osteoporotic fractures. Serum IGF-I is largely bound to
      IGF-binding protein-3 (IGFBP-3), which can inhibit IGF-I action and enhance
      delivery of IGF-I to tissues. Its role in bone biology is unclear. METHODS: Bone
      mineral density (BMD), osteoblast proliferation, and markers of bone resorption
      were examined in transgenic (Tg) mice that constitutively overexpressed human
      IGFBP-3 cDNA driven by either the cytomegalovirus (CMV) or phosphoglycerate
      kinase (PGK) promoter. RESULTS: Cultured calvarial osteoblasts from Tg mice
      expressed the transgene and grew more slowly than cells from wild-type (Wt) mice,
      and the mitogenic response to IGF-I was attenuated in osteoblasts from Tg mice.
      Total volumetric BMD and cortical BMD, measured in the femur using peripheral
      quantitative computed tomography (pQCT) were significantly reduced in both Tg
      mouse strains compared with Wt mice. PGKBP-3 Tg mice showed the most marked
      reduction in bone density. Osteocalcin levels were similar in Wt and CMVBP-3 Tg
      mice but were significantly reduced in PGKBP-3 Tg mice. Urinary deoxypyridinoline
      and osteoclast perimeter, markers of bone resorption, were significantly
      increased in both Tg mouse strains compared with Wt mice. Using double labeling
      with tetracycline, we demonstrated that pericortical and endocortical mineral
      apposition rate was significantly reduced in PGKBP-3 Tg mice compared with Wt
      mice. CONCLUSIONS: These data show that overexpression of IGFBP-3 increases
      osteoclast number and bone resorption, impairs osteoblast proliferation, and has
      a significant negative effect on bone formation.

PMID- 14584895
TI  - BMP-2 controls alkaline phosphatase expression and osteoblast mineralization by a
      Wnt autocrine loop.
AB  - Wnt/beta-catenin signaling has recently been suggested to be involved in bone
      biology. The precise role of this cascade in osteoblast differentiation was
      examined. We show that a Wnt autocrine loop mediates the induction of alkaline
      phosphatase and mineralization by BMP-2 in pre-osteoblastic cells. INTRODUCTION:
      Loss of function of LRP5 leads to osteoporosis (OPPG syndrome), and a specific
      point mutation in this same receptor results in high bone mass (HBM). Because
      LRP5 acts as a coreceptor for Wnt proteins, these findings suggest a crucial role
      for Wnt signaling in bone biology. MATERIALS AND METHODS: We have investigated
      the involvement of the Wnt/LRP5 cascade in osteoblast function by using the
      pluripotent mesenchymal cell lines C3H10T1/2, C2C12, and ST2 and the osteoblast
      cell line MC3T3-E1. Transfection experiments were carried out with a number of
      elements of the Wnt/LRP5 pathway. Measuring osteoblast and adipocyte
      differentiation markers addressed the effect of this cascade on osteoblast
      differentiation. RESULTS: In mesenchymal cells, only Wnt's capable of stabilizing
      beta-catenin induced the expression of alkaline phosphatase (ALP). Wnt3a-mediated
      ALP induction was inhibited by overexpression of either Xddl, dickkopf 1 (dkk1),
      or LRP5deltaC, indicating that canonical beta-catenin signaling is responsible
      for this activity. The use of Noggin, a bone morphogenic protein (BMP) inhibitor,
      or cyclopamine, a Hedgehog inhibitor, revealed that the induction of ALP by Wnt
      is independent of these morphogenetic proteins and does not require de novo
      protein synthesis. In contrast, blocking Wnt/LRP5 signaling or protein synthesis
      inhibited the ability of both BMP-2 and Shh to induce ALP in mesenchymal cells.
      Moreover, BMP-2 enhanced Wntl and Wnt3a expression in our cells. In MC3T3-E1
      cells, where endogenous ALP levels are maximal, antagonizing the Wnt/LRP5 pathway
      led to a decrease of ALP activity. In addition, overexpression of dkkl reduced
      extracellular matrix mineralization in a BMP-2-dependent assay. CONCLUSIONS: Our
      data strongly suggest that the capacity of BMP-2 and Shh to induce ALP relies on
      Wnt expression and the Wnt/LRP5 signaling cascade. Moreover the effects of BMP-2
      on extracellular matrix mineralization by osteoblasts are mediated, at least in
      part, by the induction of a Wnt autocrine/paracrine loop. These results may help
      to explain the phenotype of OPPG patients and HBM.

PMID- 14584896
TI  - Temporal and spatial expression profiles of BMP receptors and noggin during BMP-2
      induced ectopic bone formation.
AB  - The mechanism of ectopic bone formation has not been clear. After BMP-2
      implantation into the back muscles of 198 mice, expression of BMPR-1A, -2, and
      Noggin was increased during the early phase of the reaction. The results suggest
      that positive and negative feedback mechanisms modulate ectopic osteogenesis
      induced by this growth factor. INTRODUCTION: The expression of bone morphogenetic
      protein receptors (BMPRs) and Noggin during ectopic bone formation after
      implantation of BMP-2 into the back muscles of adult mice was investigated in
      this study. METHODS: One hundred ninety-eight male ddy mice were divided into
      groups and received either collagen disks containing BMP-2, collagen disks alone,
      or sham surgery with no disk implantation. Changes in the temporal and spatial
      expression profiles of BMPRs and Noggin were examined by Northern blotting, in
      situ hybridization, Western blotting, and immunohistochemistry. RESULTS AND
      CONCLUSIONS: In the BMP group, expression of BMPR-1A, -2, and Noggin mRNA and
      protein was enhanced 2-4 days after implantation in undifferentiated mesenchymal
      cells and regenerating muscle fibers located close to the BMP-retaining implants.
      On day 7, the expression was also observed in cartilage cells, and after day 14,
      in the osteoblastic cells around bone tissue. The level of expression peaked at
      day 4 after implantation and persisted at a much lower level during the bone
      forming process. No significant expression of BMPR-1B was detected at the mRNA
      and protein levels during the bone-forming reaction. In the BMP free control
      groups, a mild enhancement of BMPR-2 expression was also noted around the
      implant, but this was not observed for BMPR-1A, -1B, or Noggin. Upregulated
      expression of BMPR-1A, -2, and Noggin in undifferentiated mesenchymal cells and
      regenerating muscle fibers occurs during the early phase of BMP-2-induced bone
      formation. The coordinate expression of these positive and negative regulators of
      BMP signaling points to a potential regulatory mechanism for bone induction.

PMID- 14584897
TI  - Focal adhesion kinase pp125FAK interacts with the large conductance calcium
      activated hSlo potassium channel in human osteoblasts: potential role in
      mechanotransduction.
AB  - Molecular events of mechanotransduction in osteoblasts are poorly defined. We
      show that the mechanosensitive BK channels open and recruit the focal adhesion
      kinase FAK in osteoblasts on hypotonic shock. This could convert mechanical
      signals in biochemical events, leading to osteoblast activation. INTRODUCTION:
      Mechanical strains applied to the skeleton influence bone remodeling and
      architecture mainly through the osteoblast lineage. The molecular mechanisms
      involved in osteoblastic mechanotransduction include opening of mechanosensitive
      cation channels and the activation of protein tyrosine kinases, notably FAK, but
      their interplay remains poorly characterized. The large conductance K+ channel
      (BK) seems likely as a bone mechanoreceptor candidate because of its high
      expression in osteoblasts and its ability to open in response to membrane stretch
      or hypotonic shock. Propagation of the signals issued from the mechanosensitivity
      of BK channels inside the cell likely implies complex interactions with molecular
      partners involved in mechanotransduction, notably FAK. METHODS: Interaction of
      FAK with the C terminus of the hSlo alpha-subunit of BK was investigated using
      the yeast two-hybrid system as well as immunofluorescence microscopy and
      coimmunoprecipitation experiments with a rabbit anti-hslo antibody on MG63 and
      CAL72 human osteosarcoma cell lines and on normal human osteoblasts. Mapping of
      the FAK region interacting with hSlo was approached by testing the ability of
      hSlo to recruit mutated ot truncated FAK proteins. RESULTS: To the best of our
      knowledge, we provide the first evidence of the physical association of FAK with
      the intracellular part of hslo. We show that FAK/hSlo interaction likely takes
      place through the Pro-1-rich domain situated in the C-terminal region of the
      kinase. FAK/hSlo association occurs constitutively at a low, but appreciable,
      level in human osteosarcoma cells and normal human osteoblasts that express
      endogenous FAK and hSlo. In addition, we found that application of an hypo
      osmotic shock to these cells induced a sustained activation of BK channels
      associated to a marked increase in the recruitment of FAK on hSlo. CONCLUSIONS:
      Based on these data, we propose that BK channels might play a triggering role in
      the signaling cascade induced by mechanical strains in osteoblasts.

PMID- 14584898
TI  - Functional differences between growth plate apoptotic bodies and matrix vesicles.
AB  - Mineralization often occurs in areas of apoptotic changes. Our findings indicate
      that physiological mineralization is mediated by matrix vesicles. These matrix
      vesicles use mechanisms to induce mineralization that are different from the
      mechanisms used by apoptotic bodies released from apoptotic cells. Therefore,
      different therapeutic approaches must be chosen to inhibit pathological
      mineralization depending on the mechanism of mineralization (matrix vesicles
      versus apoptotic bodies). INTRODUCTION: Physiological mineralization in growth
      plate cartilage is restricted to regions of terminally differentiated and
      apoptotic chondrocytes. Pathological mineralization of tissues also often occurs
      in areas of apoptosis. We addressed the question of whether apoptotic changes
      control mineralization events or whether both events are regulated independently.
      METHODS: To induce mineralization, we treated growth plate chondrocytes with
      retinoic acid (RA); apoptosis in these cells was induced by treatment with
      staurosporine, anti-Fas, or TNFalpha. The degrees of mineralization and apoptosis
      were determined, and the structure and function of matrix vesicles and apoptotic
      bodies were compared. RESULTS: Release of matrix vesicles and mineralization in
      vivo in the growth plate occurs earlier than do apoptotic changes. To determine
      the functional relationship between apoptotic bodies and matrix vesicles, growth
      plate chondrocytes were treated with RA to induce matrix vesicle release and with
      staurosporine to induce release of apoptotic bodies. After 3 days, approximately
      90% of staurosporine-treated chondrocytes were apoptotic, whereas only 2-4% of RA
      treated cells showed apoptotic changes. RA- and staurosporine-treated chondrocyte
      cultures were mineralized after 3 days. Matrix vesicles isolated from RA-treated
      cultures and apoptotic bodies isolated from staurosporine-treated cultures were
      associated with calcium and phosphate. However, matrix vesicles were bigger than
      apoptotic bodies. Furthermore, matrix vesicles but not apoptotic bodies contained
      alkaline phosphatase and Ca2+ channel-forming annexins II, V, and VI.
      Consequently, matrix vesicles but not apoptotic bodies were able to take up Ca2+
      and form the first mineral phase inside their lumen. Mineralization of RA-treated
      cultures was inhibited by antibodies specific for annexin V but not
      mineralization of staurosporine-treated cultures. CONCLUSION: Physiological
      mineralization of growth plate chondrocytes is initiated by specialized matrix
      vesicles and requires alkaline phosphatase and annexins. In contrast, mineral
      formation mediated by apoptotic bodies occurs by a default mechanism and does not
      require alkaline phosphatase and annexins.

PMID- 14584900
TI  - Bisphosphonate therapy in primary hyperparathyroidism.

PMID- 14584899
TI  - Characterization of C4-2 prostate cancer bone metastases and their response to
      castration.
AB  - New well-characterized preclinical models of prostate cancer (CaP) bone
      metastases are needed to improve our understanding of the development of CaP
      related bone disease in patients. Here we describe characterization of a model
      consisting of direct injection of C4-2 cells into tibias. INTRODUCTION: Prostate
      cancer (CaP) has a high proclivity to metastasize to bone. Development and
      characterization of preclinical models of CaP bone metastases are of high
      interest. The objective of this study was to characterize C4-2 bone metastases
      and their response to castration. MATERIALS AND METHODS: Cell suspensions of C4
      2, a subline of LNCaP, were injected directly into the tibias of intact male
      mice. In groups A (n = 7) and B (n = 5), animals were killed 3 and 8 weeks after
      injection of C4-2 cells, respectively. In group C (n = 7), animals were castrated
      3 weeks after injection and killed 5 weeks after castration. Serum prostate
      specific antigen (PSA) levels and bone mineral density (BMD) were measured, and
      bone histomorphometric analysis was performed. RESULTS: C4-2 cells decreased BMD
      of the injected tibias by 36.1% and bone volume by 74.1% versus normal tibias.
      Castration caused a 32.3% drop in serum PSA (p = 0.0438), with a nadir at day 14,
      after which it began to rise again. Bone destruction in the tumorous tibias of
      castrated animals was decreased by 15.9% versus tumorous tibias of intact animals
      (p = 0.0392). However, BMD in the tumorous tibias of castrated mice was still
      lower than in normal tibias of intact animals. Castration also decreased BMD and
      bone volume in nontumorous tibias (p = 0.0406 and 0.0232, respectively).
      CONCLUSIONS: The C4-2 model of bone metastasis recapitulates the response to
      androgen deprivation observed in CaP patients with bone metastases and is
      suitable for study of interactions between tumor and bone cells and evaluation of
      new therapeutic modalities.

PMID- 14584901
TI  - Tartrate-resistant acid phosphatase (TRACP): a personal perspective.

PMID- 14584902
TI  - Osteoblastic tartrate-resistant acid phosphatase: its potential role in the
      molecular mechanism of osteogenic action of fluoride.
AB  - Although type 5 TRACP is recognized as a histochemical and biochemical marker of
      osteoclasts, there is evidence that bone forming cells, osteoblasts, and
      osteocytes also express a type 5 TRACP. Accordingly, an osteoblastic type 5 TRACP
      has been purified from human osteoblasts and from bovine cortical bone matrices.
      Comparison of biochemical properties of osteoblastic type 5 TRACP with those of
      osteoclastic type 5 TRACP suggests that osteoblastic type 5 TRACP is a different
      isoenzyme from osteoclastic type 5 TRACP. Two properties of osteoblastic type 5
      TRACP may be relevant to its physiological functions: (1) it acts as a protein
      tyrosine phosphatase (protein tyrosine phosphorylation) under physiologically
      relevant conditions, and (2) it is sensitive to inhibition by clinically relevant
      concentrations of fluoride. Because fluoride is a stimulator of osteoblastic
      proliferation and differentiation and a potent osteogenic agent and because
      protein tyrosine phosphorylation plays an important regulatory role in cell
      proliferation and differentiation, these unique properties and other evidence
      summarized in this review led to the proposal that the osteogenic action of
      fluoride is mediated, at least in part, by the fluoride-mediated inhibition of
      osteoblastic type 5 TRACP/protein tyrosine phosphorylation, which leads to a
      stimulation of osteoblast proliferation and differentiation, and subsequently, an
      increase in bone formation.

PMID- 14584903
TI  - Regulation of the murine TRACP gene promoter.
AB  - The activity of the TRACP promoter has been investigated as a model of gene
      regulation in osteoclasts. The murine TRACP gene promoter contains potential
      binding sites for a number of transcription factors in particular, candidate
      sites for the Ets factor PU.1 and for the microphthalmia transcription factor
      (MiTF). These are of relevance to osteoclast biology because the PU.1 knockout
      mouse has an osteopetrotic phenotype, and MiTF, when mutated in the mi/mi mouse,
      also results in osteopetrosis. The binding sites for both of these factors have
      been identified, and they have been determined to be functional in regulating
      TRACP expression. A novel assay system using the highly osteoclastogenic RAW/C4
      subclone of the murine macrophage cell line RAW264.7 was used to perform gene
      expression experiments on macrophage and osteoclast cell backgrounds. We have
      shown that TRACP expression is a target for regulation by the
      macrophage/osteoclast transcription factor PU.1 and the osteoclast commitment
      factor MiTF and that these factors act synergistically in regulating this
      promoter. This directly links two controlling factors of osteoclast
      differentiation to the expression of an effector of cell function.

PMID- 14584904
TI  - Tartrate-resistant acid phosphatase knockout mice.
AB  - TRACP is a lysosomal enzyme found in diverse tissues, where it is expressed in
      dendritic cells as well as osteoclasts and macrophages. To investigate the
      function of TRACP in vivo, we have generated mice in which the gene-encoding
      TRACP has been selectively disrupted by targeted homologous recombination in
      murine embryonic stem cells. Homozygous TRACP "knockout" mice have progressive
      foreshortening and deformity of the long bones and axial skeleton suggesting a
      role for TRACP in endochondral ossification. There is increased mineralization
      reflecting a mild osteopetrosis caused by reduced osteoclast modeling activity.
      These knockout mice also display an impairment of macrophage function with
      abnormal immunomodulatory cytokine responses. Superoxide formation and nitrite
      production were enhanced in stimulated macrophages lacking TRACP as was the
      secretion of the proinflammatory cytokines TNF-alpha, interleukin (IL)-1beta, and
      IL-12. TRACP knockout mice showed delayed clearance of the microbial pathogen
      Staphylococcus aureus after sublethal intraperitoneal inoculation. The
      macrophages lacking TRACP showed an increase in tartrate-sensitive lysosomal acid
      phosphatase activity (LAP). The TRACP knockout mice were bred with mice lacking
      LAP. Mice lacking both TRACP and LAP had even shorter bones than the TRACP single
      knockouts. Osteopontin, identical to the T-cell cytokine eta-1, accumulated
      adjacent to actively resorbing osteoclasts suggesting that both phosphatases are
      important for processing this protein. We propose that TRACP may be an important
      regulator of osteopontin/eta-1 activity common to both the immune system and
      skeleton.

PMID- 14584905
TI  - Potential function for the ROS-generating activity of TRACP.
AB  - TRACP is an enzyme with unknown biological function. It is expressed primarily in
      bone-resorbing osteoclasts and activated macrophages. In addition to its
      phosphatase activity, TRACP is capable of generating reactive oxygen species
      (ROS). In resorbing osteoclasts, TRACP is localized in transcytotic vesicles
      transporting bone matrix degradation products from the resorption lacuna to a
      functional secretory domain in the basolateral membrane. ROS generated by TRACP
      are capable of destroying organic bone matrix components, suggesting that they
      may be targeted to further destroy initial matrix degradation products in the
      transcytotic vesicles. The transcytotic route of osteoclasts is analogous with
      the antigen presentation route of macrophages transporting endocytosed foreign
      material into cell surface for presentation to other cells of the immune system.
      Macrophages overexpressing TRACP have elevated levels of intracellular ROS. In
      alveolar macrophages, TRACP is colocalized with endocytosed Staphylococcus
      aureus, a pathogen whose clearance is reduced in TRACP-deficient mice, suggesting
      that ROS generated by TRACP may be targeted to destroy foreign material in the
      antigen presentation route of macrophages. These data suggest that the ROS
      generating activity of TRACP may have an important role both in bone resorption
      and in the immune defense system.

PMID- 14584906
TI  - TRACP as an osteopontin phosphatase.
AB  - TRACP is synthesized as a latent proenzyme requiring proteolytic processing to
      attain maximal phosphatase activity. Excision of an exposed loop domain abolishes
      the interaction between the loop residue Asp146 and a ligand to the redox
      sensitive iron of the active site, most likely Asn91, providing a mechanism for
      the enzyme repression. Both cathepsin K and L efficiently cleave in the loop
      domain and activate the latent enzyme, and we propose that cathepsin K acts as a
      physiological activator of TRACP in osteoclasts, whereas cathepsin L might
      fulfill a similar role in different types of macrophages. Considering the rather
      broad substrate specificity of TRACP, a tight regulation of its activity in the
      cell appears warranted. Besides proteolytic cleavage, the enzyme should need a
      specific local environment with a slightly acidic pH and reducing equivalents to
      keep the enzyme fully active. Cellular subcompartments where these required
      conditions prevail are potential subcellular site(s) of TRACP action. Of bone
      phosphoproteins shown to be substrates for TRACP, both osteopontin and bone
      sialoprotein are colocalized with TRACP in the resorption lacuna of the
      osteoclasts, and dephosphorylation of OPN impair its ability to promote adhesion
      as well as migration of osteoclasts in vitro. A role for TRACP as an osteopontin
      phosphatase in bone is therefore suggested. The expression of TRACP as well as
      OPN in other tissues with possible interactions between the two could suggest a
      more general function for TRACP as a regulator of OPN phosphorylation and
      bioactivity.

PMID- 14584907
TI  - Disease-specific expression of tartrate-resistant acid phosphatase isoforms.
AB  - The association between elevated serum type 5 TRACP activity and metabolic bone
      diseases has been recognized for many years. However, serum type 5 TRACP exists
      as two related isoforms: 5a and 5b. Only isoform 5b is osteoclast-derived; the
      origin and significance of isoform 5a has hardly been explored. We have used
      simultaneous immunoassays for type-5 TRACP activity and total type-5 TRACP
      protein in conjunction with non-denaturing gel electrophoresis and column
      chromatography to investigate the nature and significance of TRACP isoforms 5a
      and 5b in end-stage renal disease (ESRD) and rheumatoid arthritis (RA). Our
      studies have shown that TRACP activity and protein are elevated in approximately
      50% of sera from ESRD patients, which is caused by osteoclastic isoform 5b. We
      have also shown that total TRACP protein, but not TRACP activity, is elevated in
      approximately 30% of sera from RA patients, which is caused by non-osteoclastic
      isoform 5a. When macrophages or dendritic cells (DC) were cultured in vitro,
      abundant TRACP 5a was secreted into the culture medium, whereas TRACP 5b was
      retained intracellularly by both cell types. This implicates macrophages and DC
      as potential sources of elevated TRACP 5a in RA. Because TRACP isoform expression
      may be disease-specific, it is important to be able to distinguish TRACP 5a from
      5b. There are four criteria by which to do so: (1) TRACP 5a bears sialic acid
      residues while TRACP 5b does not; (2) the pH optimum for TRACP 5a is 5.2 while
      that for TRACP 5b is 5.8; (3) the specific activity of TRACP 5a is significantly
      lower than that of TRACP 5b; and (4) TRACP 5a is as an uncleaved polypeptide,
      whereas TRACP 5b is a proteolytically nicked disulfide-linked "heterodimer." The
      differences in biochemical properties and disease-specific expression of TRACP
      isoforms 5a and 5b suggest that they are regulated differently and perform
      separate functions in a tissue-specific manner.

PMID- 14584909
TI  - A review of symptoms commonly associated with menopause: implications for
      clinical neuropsychologists and other health care providers.
AB  - Menopause is a process, either naturally or medically induced, that occurs in
      nearly all women at some point in life. Some of the most commonly reported
      symptoms associated with menopause are hot flushes/flashes, fatigue, headaches,
      irritability, insomnia, and depression. These symptoms overlap with symptoms
      commonly reported in Traumatic Brain Injury (TBI) as well as postconcussive
      syndrome. This overlap between symptoms commonly associated with menopause and
      neuropsychological conditions makes it necessary to have the base rates of these
      symptoms and conditions available. The purpose of the present review was to
      consolidate the clinical literature on the most commonly reported menopausal
      symptoms and to calculate the base rates associated with these symptoms.

PMID- 14584911
TI  - Replacement of immobilised cell bioreactors by smaller immobilised enzyme
      bioreactors: unique-outcome predictability for cytochromes P450 isoforms?
AB  - Both immobilized enzymes (IME) and immobilized cells (IMC) are acceptable as the
      biocatalysts essential for the attainment of rapid rates of bioconversion in
      bioreactors. IMC can display higher than expected cellular permeability whilst
      IME can exhibit high catalytic constant (kcat/Km) despite limitations on
      substrate utilisation due to an unstired diffusion layer of solvent. Scale-down
      switching from IMC to IME involves the replacement of high-volume biotechnology
      by low-volume biotechnology, sometimes using IME mimics in partially non-aqueous
      solvent systems. Highly purified IME systems covalently immobilised to particles
      of, for instance, microcrystalline cellulose or porous glass, can retain both the
      hydrophilic and hydrophobic intermediate products in situ of the chosen sequence
      of enzyme reactions. These bioconversions, therefore, are as efficient as those
      with IMC where enzymes are often particle- or membrane-bound so that even
      hydrophilic intermediates are not released rapidly into solution. This mimicry of
      in vivo biosynthetic pathways that are compartmentalised in vivo (e.g. of
      lysosomes, mitochondria and endoplasmic reticulum) can replace larger IMC by IME
      especially in application of up to 2700 cytochromes P450 isoforms in
      bioprocessing. In silico investigation of appropriate model IME systems, in
      comparison with IMC systems, will be needed to define the optimal bioreactor
      configuration and parameters of operation, such as pH, T and oxygen mass transfer
      rate (OTR). The application solely of hazop (applied hazard and operability
      concepts) may, nevertheless, not be recommended to replace fully the in silico
      and real-lab pilot-scale and scale studies. Here, food-safe bioprocessing has to
      be achieved without incorporation of recognised biohazards; especially in the
      form of unacceptable levels of toxic metals that promote a risk-analysis
      uncertainty.

PMID- 14584912
TI  - Optical resolution of racemic 2-hydroxy octanoic acid by lipase-catalyzed
      hydrolysis in a biphasic membrane reactor.
AB  - Racemic 2-hydroxy octanoic acid methyl ester was optically resolved by lipase
      catalyzed hydrolysis in a biphasic membrane reactor using hydrophilic/hydrophobic
      capillary membranes. In a buffer/hexane biphasic membrane reactor using
      hydrophilic ultrafiltration membranes, (S)-2-hydroxy octanoic acid was recovered
      from the aqueous phase at 59-67% yield and 0.9-0.92 enantiomeric excess (ee), and
      the ester of (R)-isomer was recovered from the organic phase at 73-75% yield and
      0.92-0.99 ee.

PMID- 14584910
TI  - The neuropsychology of heading and head trauma in Association Football (soccer):
      a review.
AB  - Association Football (soccer) is the most popular and widespread sport in the
      world. A significant proportion of the injuries suffered in football are head
      injuries involving trauma to the brain. In normal play, head trauma frequently
      arises from collisions, but some researchers have claimed that it also may arise
      as a consequence of heading the ball. Although assessments based on biomechanical
      analyses are equivocal on the potential for brain injury due to football heading,
      a growing literature seems to support the claim that neuropsychological
      impairment results from general football play and football heading in particular.
      However, this review suggests a distinction is required between the
      neuropsychological effects of concussive and subconcussive head trauma and that
      all of the neuropsychological studies conducted so far suffer from methodological
      problems. At best, a few of these studies may be regarded as exploratory. The
      review concludes that presently, although there is exploratory evidence of
      subclinical neuropsychological impairment as a consequence of football-related
      concussions, there is no reliable and certainly no definitive evidence that such
      impairment occurs as a result of general football play or normal football
      heading. The neuropsychological consequences of football-related subconcussive
      effects await confirmatory investigation.

PMID- 14584913
TI  - Antigenicity of the region encoded by exon8 of the human serine protease,
      HtrA2/Omi, is associated with its protein solubility.
AB  - HtrA2/Omi, a mitochondrial serine protease, is pivotal in regulating apoptotic
      cell death. To determine the location of antigenic determinants in HtrA2/Omi, we
      expressed a series of the N-terminally truncated HtrA2/Omi as GST fusion proteins
      in E. coli. We assessed protein solubility and antigenic reactivity of various N
      terminally truncated HtrA2/Omi proteins by binding to glutathione beads and
      immunoblot analyses, respectively. We identified that the region encoded by exon8
      of HtrA2/Omi was expressed as a highly soluble form and contains an antigenic
      determinant specifically recognized by a polyclonal serum against HtrA2/Omi. Our
      data provide evidence that protein solubility of the specific region in target
      proteins may contribute to the antigenicity.

PMID- 14584908
TI  - Processing faces and facial expressions.
AB  - This paper reviews processing of facial identity and expressions. The issue of
      independence of these two systems for these tasks has been addressed from
      different approaches over the past 25 years. More recently, neuroimaging
      techniques have provided researchers with new tools to investigate how facial
      information is processed in the brain. First, findings from "traditional"
      approaches to identity and expression processing are summarized. The review then
      covers findings from neuroimaging studies on face perception, recognition, and
      encoding. Processing of the basic facial expressions is detailed in light of
      behavioral and neuroimaging data. Whereas data from experimental and
      neuropsychological studies support the existence of two systems, the neuroimaging
      literature yields a less clear picture because it shows considerable overlap in
      activation patterns in response to the different face-processing tasks. Further,
      activation patterns in response to facial expressions support the notion of
      involved neural substrates for processing different facial expressions.

PMID- 14584915
TI  - Reaction of substituted phenols with thermostable laccase bound to Bacillus
      subtilis spores.
AB  - A strain of B. subtilis produced 1.8 times more laccase on sporulation medium
      than on non-sporulation medium. Spores oxidized mono- and di-methoxyphenols (0.1
      mM) at 50 degrees C. The half-life of laccase bound to spores was about 2 d and
      the substrate was repeatedly removed by spores recovered from the reaction
      mixture.

PMID- 14584914
TI  - Isolation and characterization of sulfur-utilizing denitrifiers from the sulfur
      oxidizing denitrification process.
AB  - Of 14 potential sulfur-oxidizing strains, Pseudomonas sp. B21 and Agrobacterium
      sp. B19 were considered as denitrifiers. Under aerobic conditions, with S0 as
      electron donor, maximum cell growth rates were 0.022 (B21) and 0.043 h(-1) (B19).
      Both grew optimally at pH 7.5 and 28 degrees C. When NO3-N was increased from 10
      to 200 mg l(-1) the efficiency of nitrate removal of each strain gradually
      decreased, from 60 to 40%. Addition of suitable organic compounds (C/N < 4.2)
      increased the nitrate removal efficiencies of both strains, indicating their
      mixotrophic characters.

PMID- 14584916
TI  - Detection of known mutations in hypertrophic cardiomyopathy using oligonucleotide
      microarrays assisted by improved base stacking hybridization.
AB  - With the assistance of improved base stacking hybridization, a low-density
      microarray, containing 12 capture probes, was used to identify 7 known
      hypertrophic cardiomyopathy-related mutations in the gene of MYH7 (beta-myosia
      heavy chain). The hybridization targets, amplified from 11 plasmids containing
      wild type or mutation sequences of MYH7 and healthy genomic DNA, were prepared by
      single-step fluorescence labeled asymmetric PCR. Six single base substitutions
      and a trinucleotide deletion were identified unambiguously, and the average
      discrimination ratio (Qmut) for artificial heterozygous samples was as high as
      16.2.

PMID- 14584917
TI  - Rapid 2,2'-bicinchoninic-based xylanase assay compatible with high throughput
      screening.
AB  - High-throughput screening requires simple assays that give reliable quantitative
      results. A microplate assay was developed for reducing sugar analysis that uses a
      2,2'-bicinchoninic-based protein reagent. Endo-1,4-beta-D-xylanase activity
      against oat spelt xylan was detected at activities of 0.002 to 0.011 IU ml(-1).
      The assay is linear for sugar concentrations from 0 to 86 microg ml(-1) and can
      also be used to assay protein concentrations (0 to 143 microg ml(-1)) on the same
      plate. A variety of temperatures and pH conditions can be used and, after
      incubation, the assay requires only one detection reagent and one heating step.

PMID- 14584918
TI  - Controlled rotation of biological microscopic objects using optical line
      tweezers.
AB  - Controlled, continuous rotation of cells or intracellular objects was achieved
      using optical tweezers with an elliptic beam profile (line tweezers), which was
      generated by placing a cylindrical lens in the path of the trapping beam. By
      rotating the cylindrical lens, rotation of the elliptic trapping beam and hence
      of the object trapped therein was achieved. Compared to previously reported
      techniques for rotation of microscopic objects, this approach is much simpler,
      gives better utilization of available laser power and also allows much easier
      control of the trap beam profile. We have used this approach for rotation of
      biological objects varying in size from 2 to 40 microm. At 25 mW trapping beam
      power at the object plane E. coli bacteria could be rotated at speeds approaching
      10 Hz and an intracellular object (presumably a calcium oxalate crystal) trapped
      inside Elodea densa plant cell could be rotated with speeds of up to 4 Hz. To our
      knowledge, this is the first report for rotation of an intracellular object.

PMID- 14584919
TI  - Expression and production of bioactive human interleukin-18 in transgenic tobacco
      plants.
AB  - The cDNA of human interleukin-18 (hIL-18) was successfully inserted into the
      genome of tobacco plant, Nicotiana tabacum cv. NC-89, using Agrobacterium
      tumefaciens-mediated transformation. Insertion and translation of hIL-18 in
      transformants were confirmed by PCR, ELISA, and Western blot, respectively. The
      transformed extracts contained the recombinant hIL-18 protein up to 0.05% of
      total soluble protein. Activity of the recombinant hIL-18 in plant cells was
      confirmed by the induction of IFN-gamma on IL-18-responsive J6-1 cells by the
      extracts obtained from the transformants. The expression level of hIL-18 (351 ng
      g(-1) tobacco tissue) obtained in the present study may be sufficient to induce
      responses/effects in vivo.

PMID- 14584921
TI  - High-throughput screening for gene libraries expressing carbohydrate hydrolase
      activity.
AB  - A simple and fast method is described allowing screening of large number of
      Escherichia coli clones (4000 per day) for the presence of functional or improved
      carbohydrate hydrolase enzymes. The procedure is relatively cheap and has the
      advantage that carbohydrate degrading activity can be directly measured using
      liquid cultures grown in microtiter plates without the need of separation or
      purification steps.

PMID- 14584920
TI  - Simple detection of point mutations in DNA oligonucleotides using SYBR Green I.
AB  - A novel and simple method for detection of mutations in DNA oligonucleotides
      using a double-stranded DNA specific dye (SYBR Green I) is reported. The SYBR
      Green I is bound specifically with a duplex DNA oligonucleotide (it tercalation).
      This intercalation induces fluorescent emission at 525 nm with excitation at 494
      nm. The fluorescence intensity of mismatched oligonucleotides (40-mer) decreases
      (by more than 13%) in comparison with the perfectly matched oligonucleotides.
      Moreover, fluorescence measurement of the SYBR Green I can distinguish various
      types of single-base mismatches, except for the T-G terminal mismatch. The
      addition of 20% (v/v) formamide, however, to an oligonucleotide solution improved
      the sensitivity of detection and also enabled the detection of the T-G terminal
      mismatch. This detection method requires only a normal fluorescence
      spectrophotometer, an inexpensive dye and just 50 pmol of sample DNA.

PMID- 14584922
TI  - Stability of plasmid pA387 derivatives in Amycolatopsis mediterranei producing
      rifamycin.
AB  - Genetic studies on the biosynthesis of rifamycins in producer strains such as
      Amylcolaptopsis mediterranei U-32 are severely hampered by the availability of
      efficient transformation procedures and stable plasmid vectors. Using an
      efficient electroporation procedure we have studied the replication and stability
      of a pA387 derivative, pDXM32. This plasmid confers enhanced plasmid stability
      and copy number compared to pA387 derivatives commonly used as cloning vectors in
      A. mediterranei. Deletion derivatives in the region previously identified as
      being a minimal replication origin were also examined with respect to their
      ability to transform A. mediterranei and at least one locus was essential for
      replication. A 5.4 kbp DNA fragment was sequenced and annotated encoding the
      replication and plasmid stability functions. A parA homologue was identified
      which is likely to confer plasmid stability.

PMID- 14584923
TI  - Serine substitution for cysteine residues in levansucrase selectively abolishes
      levan forming activity.
AB  - Levansucrase is responsible for levan formation during sucrose fermentation of
      Zymomonas mobilis, and this decreases the efficiency of ethanol production. As
      thiol modifying agents decrease levan formation, a role for cysteine residues in
      levansucrase activity has been examined using derivatives of Z. mobilis
      levansucrase that carry serine substitutions of cysteine at positions 121, 151 or
      244. These substitutions abolished the levan forming activity of levansucrase
      whilst only halving its activity in sucrose hydrolysis. Thus, polymerase and
      hydrolase activities of Z. mobilis levansucrase are separate and have different
      requirements for the enzyme's cysteine residues.

PMID- 14584924
TI  - Removal of low molecular weight phenols from olive oil mill wastewater using
      microalgae.
AB  - The treatment of olive oil mill wastewater (OMW) with two phenol resistant algae,
      Ankistrodesmus braunii and Scenedesmus quadricauda, showed a limited reduction of
      phenol content after 5 d of treatment, irrespective of algal concentration.
      Otherwise, cultures of both algae, grown in the dark, degraded over 50% of the
      low molecular weight phenols contained in OMW, but they were not completely
      removed, but were biotransformed into other non-identified, aromatic compounds.

PMID- 14584925
TI  - Making thin polymeric materials, including fabrics, microbicidal and also water
      repellent.
AB  - A procedure is developed and validated for making a non-functionalized polyolefin
      fabric/film highly bactericidal and fungicidal which involves a free-radical
      grafting of maleic anhydride, followed by an attachment of polyethylenimine (PEI)
      and its subsequent N-alkylation. Separately, cotton fabric coated with a micron
      layer of a hydrophobic polymer using hot-filament chemical vapor deposition is
      rendered markedly hydrophobic; if this coating is preceded by immobilization of N
      alkyl-PEI, the fabric becomes both water-repellent and bactericidal.

PMID- 14584926
TI  - Kinetics of enhanced thermostability of an extracellular glucoamylase from
      Arachniotus sp.
AB  - Purified extracelluar glucoamylase from Arachniotus sp. was used for kinetic and
      thermodynamic characterization. Thermal inactivation followed first order
      kinetics. The denaturation/activation energies of enzyme were 57 and 89 kJ mol(
      1), respectively. Both enthalpy and entropy of activation for inactivation were
      lower than those for glucoamylases reported in literature. It is suggested that
      the enzyme is highly thermostable and is suitable for industrial applications.

PMID- 14584927
TI  - Selection and characterization of peptide memitopes binding to ricin.
AB  - A combinatorial random peptide display library expressed in E. coli was employed
      to identify short, linear peptide sequences that showed affinity for ricin and
      could be used as reagents for detection and identification of ricin. One peptide,
      P3, from a collection of four short peptides showed specific binding to ricin.
      The kinetic analysis of this peptide binding to the ricin showed lower
      equilibrium binding constants for the peptide P3 than monoclonal antibody. This
      is attributed due to both slower association and faster dissociation rates for
      the peptide P3. The random ricin peptide P3 binds to ricin with a KD of 1 microM
      versus the antibody's KD of 14 nM. This particular peptide memitope P3 against
      ricin showed specific binding to ricin without any significant cross-reactivity
      against other proteins such as bovine serum albumin (BSA), lysozyme and natural
      bacterial toxins such as Staphylococcal enterotoxins A and B. The results
      provided proof-of-principal that peptide memitopes are another choice of reagents
      due to ease in production to be used for the detection of highly toxic bio-threat
      or biowarfare agents such as ricin.

PMID- 14584928
TI  - Morphological quantification of pellets in Streptomyces hygroscopicus var.
      geldanus fermentation broths using a flatbed scanner.
AB  - An image analysis technique has been developed to allow high throughput
      morphological characterisation of microbial fermentation broths containing
      spherical pellets greater than 100 microm in diameter. Images of stained
      Streptomyces hygroscopicus var. geldanus culture samples at three different
      inoculum levels were captured using a flatbed scanner, at a resolution of 21
      microm per pixel (1200 dots per inch) and subsequently analysed leading to the
      generation of a morphological profile of each sample. The time taken for image
      capture and analysis of a prepared sample, containing approx. 2000 particles, was
      3 min 6 s.

PMID- 14584929
TI  - Multidrug resistance reversal agents.

PMID- 14584930
TI  - Nitroaryl phosphoramides as novel prodrugs for E. coli nitroreductase activation
      in enzyme prodrug therapy.
AB  - Cyclic and acyclic nitroaryl phosphoramide mustard analogues were activated by E.
      coli nitroreductase, an enzyme explored in GDEPT. The more active acyclic 4
      nitrobenzyl phosphoramide mustard (7) showed 167 500x selective cytotoxicity
      toward nitroreductase-expressing V79 cells with an IC(50) as low as 0.4 nM. This
      is about 100x more active and 27x more selective than CB1954 (1). The superior
      activity was attributed to its better substrate activity (k(cat)/K(m) 19x better
      than 1) and/or excellent cytotoxicity of phosphoramide mustard released.

PMID- 14584931
TI  - Synthesis and biological evaluation of 2'-methyl taxoids derived from baccatin
      III and 14beta-OH-baccatin III 1,14-carbonate.
AB  - A series of 2'-methyl taxoids were synthesized and essayed for growth inhibition
      experiments conducted in human ovarian cancer cell line A2780wt and its
      counterparts A2780cis, A2780tax, and A2780adr, resistant to cisplatin,
      paclitaxel, and doxorubicin, respectively, to test the effect of this substituent
      on the antitumor activity. Additional experiments were performed on MCF-7 human
      breast cancer cell line and MCF7-R resistant to doxorubicin. In several cases
      these taxoids were more active than paclitaxel showing subnanomolar IC(50)
      values.

PMID- 14584932
TI  - Discovery of (aryloxopropenyl)pyrrolyl hydroxyamides as selective inhibitors of
      class IIa histone deacetylase homologue HD1-A.
AB  - Chemical manipulations performed on aroyl pyrrolyl hydroxyamides, a new class of
      HDAC inhibitors previously reported by us, led to (aryloxopropenyl)pyrrolyl
      hydroxyamides 3a-g. Such compounds, showing better inhibitory activity against
      maize HD1-A than HD1-B (two homologues of mammalian class IIa and I HDACs,
      respectively), are the first class of IIa-selective inhibitors (fold selectivity:
      7-78). They could be useful as tools for probing the biology of these enzymes and
      eventually as new anticancer agents with low toxicity.

PMID- 14584933
TI  - Dissociation of antibacterial and hemolytic activities of an amphipathic peptide
      antibiotic.
AB  - Using an alanine-scanning method, we have found that the antibacterial and
      hemolytic activities of the amphipathic cyclic decapeptide antibiotic tyrocidine
      A depend on different structural components. Single substitution of glutamine-6
      of the natural product with a cationic amino acid results in a therapeutic index
      enhancement of up to 140-fold. Successful dissociation of the two intimately
      associated properties should enable discovery of novel analogues with both high
      bacterial selectivity and antibacterial potency to counter microbial resistance.

PMID- 14584934
TI  - Identification of a potent and selective 5-HT(6) antagonist: one-step synthesis
      of (E)-3-(benzenesulfonyl)-2- (methylsulfanyl)pyrido[1,2-a]pyrimidin-4
      ylidenamine from 2-(benzenesulfonyl)-3,3-bis(methylsulfanyl)acrylonitrile.
AB  - (E)-3-(Benzenesulfonyl)-2-(methylsulfanyl)pyrido[1,2-a]pyrimidin-4-ylidenamine
      (7) was found to be a potent and selective 5-HT(6) antagonist. A one-step
      synthesis of this compound is described.

PMID- 14584935
TI  - Conformational study of lipophilic ligands in phospholipid model membrane systems
      by solution NMR.
AB  - Phospholipid bicelles were employed as a membrane bilayer model in the
      conformational studies of two lipophilic cannabinoids, delta(8)-THC and its O
      methyl ether analogue, Me-Delta(8)-THC using conventional high-resolution NMR. A
      preparation of 8% (w/v) phospholipid concentration and a high DMPC/DHPC ratio (q
      = 2.0) was found to be optimal for not only effectively incorporating our
      ligands, but also providing a more bilayerlike environment suitable for
      conformational studies. While the conformational differences between the two
      cannabinoids could not be observed in chloroform and were barely detectable in
      SDS micelle solution, there is an increasing preference for the pentyl tail of
      Delta(8)-THC to bend toward the tricyclic ring system with increasing proportions
      of DMPC in the bicelle preparation. Our results highlight the advantages of
      exploring the conformational properties of cannabinoids using bicelle
      preparations as a medium that more closely resembles biological membrane bilayers
      and eliminates the need for isotopic labeling. This approach should also be of
      more general value for studying the interactions of other cannabinoids and
      biologically active, hydrophobic or amphipathic, small molecules with membranes.

PMID- 14584936
TI  - Modeling the adenosine receptors: comparison of the binding domains of A2A
      agonists and antagonists.
AB  - A three-dimensional model of the human A(2A) adenosine receptor (AR) and its
      docked ligands was built by homology to rhodopsin and validated with site
      directed mutagenesis and the synthesis of chemically complementary agonists.
      Different binding modes of A(2A)AR antagonists and agonists were compared by
      using the FlexiDock automated docking procedure, with manual adjustment. Putative
      binding regions for the 9H-purine ring in agonist NECA 3 and the 1H
      [1,2,4]triazolo[1,5-c]quinazoline ring in antagonist CGS15943 1 overlapped, and
      the exocyclic amino groups of each were H-bonded to the side chain of N(6.55).
      For bound agonist, H-bonds formed between the ribose 3'- and 5'-substituents and
      the hydrophilic amino acids T(3.36), S(7.42), and H(7.43), and the terminal
      methyl group of the 5'-uronamide interacted with the hydrophobic side chain of
      F(6.44). Formation of the agonist complex destabilized the ground-state structure
      of the A(2A)AR, which was stabilized through a network of H-bonding and
      hydrophobic interactions in the transmembrane helical domain (TM) regions,
      facilitating a conformational change upon activation. Both flexibility of the
      ribose moiety, required for the movement of TM6, and its H-bonding to the
      receptor were important for agonism. Two sets of interhelical H-bonds involved
      residues conserved among ARs but not in rhodopsin: (1) E13(1.39) and H278(7.43)
      and (2) D52(2.50), with the highly conserved amino acids N280(7.45) and
      S281(7.46), and N284(7.49) with S91(3.39). Most of the amino acid residues lining
      the putative binding site(s) were conserved among the four AR subtypes. The
      A(2A)AR/3 complex showed a preference for an intermediate conformation about the
      glycosidic bond, unlike in the A(3)AR/3 complex, which featured an anti
      conformation. Hydrophilic amino acids of TMs 3 and 7 (ribose-binding region) were
      replaced with anionic residues for enhanced binding to amine-derivatized
      agonists. We identified new neoceptor (T88D)-neoligand pairs that were consistent
      with the model.

PMID- 14584937
TI  - Synthesis and Ca2+-mobilizing activity of purine-modified mimics of adenophostin
      A: a model for the adenophostin-Ins(1,4,5)P3 receptor interaction.
AB  - The synthesis of a series of adenophostin A analogues modified at C-6 and C-2 of
      adenine is described. The target compounds were synthesized by a convergent route
      involving a modified Vorbruggen condensation of either 6-chloropurine or 2,6
      dichloropurine with a protected disaccharide, yielding two versatile
      intermediates capable of undergoing substitution with a range of nucleophiles.
      The new analogues showed a range of abilities to mobilize Ca(2+) from the
      intracellular stores of permeabilized hepatocytes and are among the first totally
      synthetic compounds to approach the activity of adenophostin A. In agreement with
      the biological results, docking studies of adenophostin A using the recently
      reported X-ray crystal structure of the type 1 Ins(1,4,5)P(3) receptor binding
      core suggested that, in likely binding modes of adenophostin A, the area around
      N(6) may be relatively open, identifying this region of the adenophostin A
      molecule as a promising target for further elaboration. The docking results also
      point to specific interactions involving residues within the binding domain of
      the Ins(1,4,5)P(3) receptor that may be involved in the molecular recognition of
      the adenophostins.

PMID- 14584938
TI  - Design, synthesis, and biological evaluation of 6-substituted-3-(4
      methanesulfonylphenyl)-4-phenylpyran-2-ones: a novel class of diarylheterocyclic
      selective cyclooxygenase-2 inhibitors.
AB  - A group of 6-alkyl (alkoxy or alkylthio)-4-aryl-3-(4-methanesulfonylphenyl)pyran
      2-ones (14a-v), possessing either a H or F substituent at the para-position of
      the C-4 phenyl ring, were designed for evaluation as selective cyclooxygenase-2
      (COX-2) inhibitors with in vivo antiinflammatory-analgesic activities. Although 6
      ethylthio-3-(4-methanesulfonylphenyl)-4-phenylpyran-2-one (14s) exhibited a very
      high in vitro COX-2 inhibitory potency (IC(50) = 0.0032 muM) and COX-2
      selectivity (SI > 120 000), 14s exhibited moderate antiinflammatory activity
      compared to celecoxib in a carrageenan-induced rat paw edema assay. In contrast,
      the less potent (IC(50) = 0.10 muM), and less selective (SI = 2880) COX-2
      inhibitor 6-ethoxy-3-(4-methanesulfonylphenyl)-4-phenylpyran-2-one (14i)
      exhibited good antiinflammatory activity where a 1 mg/kg oral dose reduced
      inflammation 32 and 67% at 3 and 5 h postdrug administration relative to the
      reference drug celecoxib where a 50 mg/kg oral dose reduced inflammation by 79
      and 58% at the respective 3 and 5 h time periods. Molecular modeling studies,
      where 14i was docked in the active site of both COX-1 and COX-2, reveals that the
      C-6 ethoxy substituent orients the pyran-2-one ring to position the SO(2)Me
      pharmacophore in the vicinity of the secondary pocket in COX-2. The absence of
      this COX-2 secondary pocket in the COX-1 binding site is due to the presence of
      the bulky Ile(523) in COX-1 such that access to the amino acid residues
      (Ile(517), Phe(518), Gln(192), and His(90)), which line the COX-2 secondary
      pocket with which the SO(2)Me pharmacophore could interact, is hindered. The six
      membered pyran-2-one ring system is a suitable central template to design
      selective COX-2 inhibitors.

PMID- 14584939
TI  - Large dimeric ligands with favorable pharmacokinetic properties and peroxisome
      proliferator-activated receptor agonist activity in vitro and in vivo.
AB  - Two potent nonselective, but PPARalpha-preferring, PPAR agonists 5 and 6 were
      designed and synthesized in high yields. The concept of dimeric ligands in
      transcription factors was investigated by synthesizing and testing the
      corresponding dimers 7, 8a, and 8b in PPAR transactivation assays. The three
      dimeric ligands all showed agonist activity on all three PPAR receptor subtypes,
      but with different profiles compared to the monomers 5 and 6. Despite breaking
      all the "rule of five" criteria, the dimers had excellent oral bioavailability
      and pharmacokinetic properties, resulting in good in vivo efficacy in db/db mice.
      X-ray crystal structure and modeling experiments suggested that the dimers
      interacted with the AF-2 helix as well as with amino acid residues in the
      lipophilic pocket close to the receptor surface.

PMID- 14584940
TI  - Prazosin-related compounds. Effect of transforming the piperazinylquinazoline
      moiety into an aminomethyltetrahydroacridine system on the affinity for alpha1
      adrenoreceptors.
AB  - In a search for structurally new alpha(1)-adrenoreceptor (alpha(1)-AR)
      antagonists, prazosin (1)-related compounds 2-11 were synthesized and their
      affinity profiles were assessed by functional experiments in isolated rat vas
      deferens (alpha(1A)), spleen (alpha(1B)), and aorta (alpha(1D)) and by binding
      assays in CHO cells expressing human cloned alpha(1)-AR subtypes. Transformation
      of the piperazinylquinazoline moiety of 1 into an aminomethyltetrahydroacridine
      system afforded compound 2, endowed with reduced affinity, in particular for the
      alpha(1A)-AR subtype. Then, to investigate the optimal features of the tricyclic
      moiety, the aliphatic ring of 2 was modified by synthesizing the lower and higher
      homologues 3 and 4. An analysis of the pharmacological profile, together with a
      molecular modeling study, indicated the tetrahydroacridine moiety as the most
      promising skeleton for alpha(1)-antagonism. Compounds 5-8, where the replacement
      of the furoyl group of 2 with a benzoyl moiety afforded the possibility to
      evaluate the effect of the substituent trifluoromethyl on receptor binding,
      resulted, except for 7, in a rather surprising selectivity toward alpha(1B)-AR,
      in particular vs the alpha(1A) subtype. Also the insertion of the 2,6
      dimethoxyphenoxyethyl function of WB 4101 on the tetrahydroacridine skeleton of
      2, and/or the replacement of the aromatic amino function with a hydroxy group,
      affording derivatives 9-11, resulted in alpha(1B)-AR selectivity also vs the
      alpha(1D) subtype. On the basis of these results, the tetrahydroacridine moiety
      emerged as a promising tool for the characterization of the alpha(1)-AR, owing to
      the receptor subtype selectivity achieved by an appropriate modification of the
      lateral substituents.

PMID- 14584941
TI  - Multivalent antibiotics via metal complexes: potent divalent vancomycins against
      vancomycin-resistant enterococci.
AB  - Dimers of vancomycin (Van), linked by a rigid metal complex,
      [Pt(en)(H(2)O)(2)](2+), exhibit potent activities (MIC approximately 0.8 mug/mL,
      approximately 720 times more potent than that of Van itself) against vancomycin
      resistant enterococci (VRE). The result suggests that combining metal
      complexation and receptor/ligand interaction offers a useful method to construct
      multivalent inhibitors.

PMID- 14584942
TI  - Potent and selective inhibitors of platelet-derived growth factor receptor
      phosphorylation. 3. Replacement of quinazoline moiety and improvement of
      metabolic polymorphism of 4-[4-(N-substituted (thio)carbamoyl)-1-piperazinyl]-6,7
      dimethoxyquinazoline derivatives.
AB  - We have previously reported that a series of 4-[4-(N-substituted (thio)carbamoyl)
      1-piperazinyl]-6,7-dimethoxyquinazoline derivatives were potent and selective
      inhibitors of platelet-derived growth factor receptor (PDGFR) phosphorylation and
      demonstrated several biological effects such as suppression of neointima
      formation following balloon injury in rat carotid artery by oral administration.
      Here, we investigated structure-activity relationships of the 6,7
      dimethoxyquinazolinyl moiety. In regard to 6,7-dimethoxy groups, ethoxy analogues
      showed potent activity (IC(50) of 16b is 0.04 microM; IC(50) of 17a is 0.01
      microM) and further extension of the alkyl group reduced activity. Interestingly,
      methoxyethoxy (IC(50) of 16j is 0.02 microM; IC(50) of 17h is 0.01 microM) and
      ethoxyethoxy (IC(50) of 17j is 0.02 micro M) analogues showed the most potent
      activity, suggesting that the inserted oxygen atom significantly interacts with
      beta-PDGFR. Among tricyclic quinazoline derivatives, the 2-oxoimidazo[4,5
      e]quinazoline derivative 21a showed potent activity (IC(50) = 0.10 microM).
      Regarding replacements of quinazoline by other heterocyclic rings, pyrazolo[3,4
      d]pyrimidine (39a, IC(50) = 0.17 microM) and quinoline (IC(50) of 40a is 0.18
      microM; IC(50) of 40b is 0.09 microM) derivatives showed potent activity.
      Isoquinoline and some pyridopyrimidine derivatives were completely inactive;
      therefore, 1-aza has an important role. Also 7-aza and 8-aza substitution on the
      parent quinazoline ring has a detrimental effect on the interaction with beta
      PDGFR. We also demonstrated that the substituents on the quinazoline ring possess
      major consequences for metabolic polymorphism. Although there existed extensive
      metabolizers and poor metabolizers in Sprague-Dawley rats administrated 6,7
      dimethoxyquinazoline derivatives (1b and 1c), 6-(2-methoxy)ethoxy-7
      methoxyquinazoline analogue 16k showed no metabolic polymorphism.

PMID- 14584943
TI  - Synthesis, characterization, and biological properties of 8-azido- and 8-amino
      substituted 2',5'-oligoadenylates.
AB  - A series of 8-azido- and 8-amino-substituted 2',5'-oligoadenylatyes was prepared
      by a uranyl-ion catalyzed polymerization of the corresponding 8-substituted
      adenosine phosphorimidazolide. Subsequent 5'-dephosphorylation of the resulting
      5'-phosphoryl 2',5'-linked oligomers with alkaline phosphatase gave the
      corresponding core oligomers. The CD spectra indicated that the 8-aminoadenosine
      analogue of the 2',5'-linked trimer has an anti-orientation as in naturally
      occurring 2',5'-oligoadenylates, while 8-azido-substituted 2',5'-oligoadenylates
      have a syn-orientation. The 8-substituted oligomers showed enhanced resistance
      against digestion by snake venom phosphodiesterase. The 2',5'-linked 8
      azidoadenylate trimer and tetramer displayed strong RNase L binding and
      activating ability, although the corresponding dimer is devoid of such
      activities. In contrast, very low or no RNase L binding and activating ability
      were observed in the 8-aminoadenosine analogue of 2',5'-oligoadenylates. Results
      indicate that the bulkiness and ionic character of the 8-substituting group have
      significant effects on the ability of these analogues to bind and activate RNase
      L. Furthermore, the orientation of the glycosidic base in the 2-5A analogues may
      change from syn to anti during binding to RNase L. The 8-azidoadenosine analogues
      of 2-5A will be useful tools in the photoaffinity labeling of RNase L, due to
      their strong RNase L binding ability. In addition, these 8-azidoadenosine
      compounds may be considered as candidates for experimental therapeutic agents
      because they have enhanced stability to enzyme degradation while retaining the
      ability to activate RNase L.

PMID- 14584944
TI  - Isoquine and related amodiaquine analogues: a new generation of improved 4
      aminoquinoline antimalarials.
AB  - Amodiaquine (AQ) (2) is a 4-aminoquinoline antimalarial that can cause adverse
      side effects including agranulocytosis and liver damage. The observed drug
      toxicity is believed to involve the formation of an electrophilic metabolite,
      amodiaquine quinoneimine (AQQI), which can bind to cellular macromolecules and
      initiate hypersensitivity reactions. We proposed that interchange of the 3'
      hydroxyl and the 4' Mannich side-chain function of amodiaquine would provide a
      new series of analogues that cannot form toxic quinoneimine metabolites via
      cytochrome P450-mediated metabolism. By a simple two-step procedure, 10 isomeric
      amodiaquine analogues were prepared and subsequently examined against the
      chloroquine resistant K1 and sensitive HB3 strains of Plasmodium falciparum in
      vitro. Several analogues displayed potent antimalarial activity against both
      strains. On the basis of the results of in vitro testing, isoquine (ISQ1 (3a))
      (IC(50) = 6.01 nM +/- 8.0 versus K1 strain), the direct isomer of amodiaquine,
      was selected for in vivo antimalarial assessment. The potent in vitro
      antimalarial activity of isoquine was translated into excellent oral in vivo
      ED(50) activity of 1.6 and 3.7 mg/kg against the P. yoelii NS strain compared to
      7.9 and 7.4 mg/kg for amodiaquine. Subsequent metabolism studies in the rat model
      demonstrated that isoquine does not undergo in vivo bioactivation, as evidenced
      by the complete lack of glutathione metabolites in bile. In sharp contrast to
      amodiaquine, isoquine (and Phase I metabolites) undergoes clearance by Phase II
      glucuronidation. On the basis of these promising initial studies, isoquine (ISQ1
      (3a)) represents a new second generation lead worthy of further investigation as
      a cost-effective and potentially safer alternative to amodiaquine.

PMID- 14584945
TI  - Synthesis, characterization, and in vitro antitumor activity of osteotropic
      diam(m)ineplatinum(II) complexes bearing a N,N-bis(phosphonomethyl)glycine
      ligand.
AB  - A series of osteotropic (bone-seeking) [(bis(phosphonomethyl)amino-kappaN)acetato
      kappaO(2-)]platinum(II) complexes attached to diammine, ethane-1,2-diamine, cis
      R,S-cyclohexane-1,2-diamine, trans-S,S-cyclohexane-1,2-diamine, or trans-R,R
      cyclohexane-1,2-diamine has been synthesized in accord with the concept of drug
      targeting and characterized by elemental analysis, (1)H, (13)C, and (31)P NMR
      spectroscopy. The in vitro antitumor activity in ovarian cancer cells (CH1) has
      been determined by means of the MTT assay. In this cisplatin-sensitive cell line
      the complexes containing cyclohexane-1,2-diamine (chxn) displayed a high activity
      in comparison to the diammine and ethane-1,2-diamine counterparts. In agreement
      with structure-activity relationships of other chxn-containing platinum(II)
      complexes both [(bis(phosphonomethyl)amino-kappaN)acetato-kappaO(2-)](trans
      cyclohexane-1,2-diamine)platinum(II) complexes show superior potency than the
      corresponding cis-congener whereas the trans-R,R isomer displays the highest
      activity. Within the series of complexes under investigation, potency decreases
      depending on the coordinated amine ligand in the following order: trans-R,R-chxn
      > trans-S,S-chxn > NH(3) > or = cis-R,S-chxn > en.

PMID- 14584946
TI  - Design and synthesis of trans-3-(2-(4-((3-(3-(5-methyl-1,2,4-oxadiazolyl))-
      phenyl)carboxamido)cyclohexyl)ethyl)-7-methylsulfonyl-2,3,4,5-tetrahydro-1H-3
      benzazepine (SB-414796): a potent and selective dopamine D3 receptor antagonist.
AB  - At their clinical doses, current antipsychotic agents share the property of both
      dopamine D(2) and D(3) receptor blockade. However, a major disadvantage of many
      current medications are the observed extrapyramidal side-effects (EPS),
      postulated to arise from D(2) receptor antagonism. Consequently, a selective
      dopamine D(3) receptor antagonist could offer an attractive antipsychotic
      therapy, devoid of the unwanted EPS. Using SAR information gained in two
      previously reported series of potent and selective D(3) receptor antagonists, as
      exemplified by the 2,3,4,5-tetrahydro-1H-3-benzazepine 10 and the 2,3-dihydro-1H
      isoindoline 11, a range of 7-sulfonyloxy- and 7-sulfonylbenzazepines has been
      prepared. Compounds of this type combined a high level of D(3) affinity and
      selectivity vs D(2) with an excellent pharmacokinetic profile in the rat.
      Subsequent optimization of this series to improve selectivity over a range of
      receptors and reduce cytochrome P450 inhibitory potential gave trans-3-(2-(4-((3
      (3-(5-methyl-1,2,4-oxidiazolyl))phenyl)carboxamido)cyclohexyl)ethyl)-7
      methylsulfonyl-2,3,4,5-tetrahydro-1H-3-benzazepine (58, SB-414796). This compound
      is a potent and selective dopamine D(3) receptor antagonist with high oral
      bioavailability and is CNS penetrant in the rat. Subsequent evaluation in the rat
      has shown that 58 preferentially reduces firing of dopaminergic cells in the
      ventral tegmental area (A10) compared to the substantia nigra (A9), an
      observation consistent with a prediction for atypical antipsychotic efficacy. In
      a separate study, 58 has been shown to block expression of the conditioned place
      preference (CPP) response to cocaine in male rats, suggesting that it may also
      have a role in the treatment of cue-induced relapse in drug-free cocaine addicts.

PMID- 14584947
TI  - Structure-activity relationships of gamma-MSH analogues at the human melanocortin
      MC3, MC4, and MC5 receptors. Discovery of highly selective hMC3R, hMC4R, and
      hMC5R analogues.
AB  - It has been shown by extensive studies that melanotropin bioactivities are
      critically dependent on the core or central tetrapeptide sequence, His-Phe-Arg
      Trp, and in alpha-MSH it has been demonstrated further that a reverse-turn type
      conformation exists at this pharmacophore. To probe the receptor active
      conformation of the pharmacophore His-Phe-Arg-Trp in gamma-MSH, two different
      series of gamma-MSH analogues have been designed and synthesized and their
      biological activities determined at hMC3R, hMC4R, and hMC5R. The 1st series
      consists of a cyclic scan using different disulfides or lactam bridges. It was
      found that cyclization of the native gamma-MSH around the highly conserved
      sequence can lead to shifts in affinity and selectivity for hMC4R instead of the
      hMC3R as seen in the native peptide. Furthermore, a 23-membered ring is desirable
      for potency (e.g., analogues 6 and 10) whereas a 26-membered ring (analogue 1, H
      Tyr-Val-c[Cys-Gly-His-Phe-Arg-Trp-Cys]-Arg-Phe-Gly-NH(2) with Gly(4)) is more
      important for selectivity. The 2nd series is made of d-2-naphthylalanine (d
      Nal(2')) scan of the gamma-MSH sequence at position 6 and 8 and the replacement
      of His(5) with Pro (analogue 13). Analogue 12, H-Tyr-Val-Nle-Gly-His-Phe-Arg-d
      Nal(2')-Asp-Arg-Phe-Gly-NH(2), is a potent and selective antagonist at the hMC4R,
      and analogue 15, H-Tyr-Val-Nle-Gly-Aib-Phe-Arg-d-Nal(2')-Asp-Arg-Phe-Gly-NH(2),
      is a highly selective and potent agonist of the hMC5R. A most promising analogue
      is 13, H-Tyr-Val-Nle-Gly-Pro-d-Nal(2')-Arg-Trp-Asp-Arg-Phe-Gly-NH(2), which is a
      very potent agonist of the hMC4R, and this analogue can be further evaluated for
      feeding behavior and the regulation of fat stores.

PMID- 14584949
TI  - Three-dimensional quantitative structure-activity relationship analysis of
      propafenone-type multidrug resistance modulators: influence of variable selection
      on test set predictivity.
AB  - An extended set of multidrug-resistance modulators of the propafenone type were
      investigated using CoMFA and CoMSIA. A number of 3D-QSAR models were derived from
      steric, electrostatic, and hydrophobic fields and their combinations. The
      hydrophobic fields alone and in combination with the steric and both (steric and
      electrostatic) fields yielded the models with the highest cross-validated
      predictivity, in agreement with a previous analysis of a smaller data set of
      propafenone-type multidrug-resistance (MDR) modulators. Inclusion of
      lipophilicity did not lead to an improvement of the models. The results point to
      the importance of hydrophobicity as a space-directed molecular property for MDR
      modulating activity. The influence of variable selection applying the GOLPE
      procedure was investigated with an external test set. Variable-selection
      procedure was repetitively applied, keeping at each stage variables with
      uncertain contribution to the models. For the CoMFA-based 3D-QSAR models, an
      increase in external prediction quality was found. In contrast, the CoMSIA-based
      3D-QSAR models were not improved by the GOLPE variable-selection procedure.

PMID- 14584950
TI  - Design, synthesis, and SAR of potent and selective dipeptide-derived inhibitors
      for dipeptidyl peptidases.
AB  - In this paper we report the systematic search for new, potent, and selective DPP
      II inhibitors. A study of the structure-activity relationship was conducted
      starting from aminoacyl pyrrolidides as lead compounds. Rational exploration of
      the P(1) and P(2) building blocks led to the discovery of some very potent DPP II
      inhibitors which can be characterized by their high selectivity for DPP II with
      regard to DPP IV. Dab-Pip and Dab-Pip-2-CN were selected as the most promising
      inhibitors (IC(50) nM range) and will enable us to study the physiological role
      of DPP II and to differentiate between DPP II and DPP IV in biological systems.

PMID- 14584948
TI  - 2-Substitution of adenine nucleotide analogues containing a bicyclo[3.1.0]hexane
      ring system locked in a northern conformation: enhanced potency as P2Y1 receptor
      antagonists.
AB  - Preference for the northern (N) ring conformation of the ribose moiety of adenine
      nucleotide 3',5'-bisphosphate antagonists of P2Y(1) receptors was established by
      using a ring-constrained methanocarba (a bicyclo[3.1.0]hexane) ring as a ribose
      substitute (Nandanan et al. J. Med. Chem. 2000, 43, 829-842). We have now
      combined the ring-constrained (N)-methanocarba modification with other
      functionalities at the 2-position of the adenine moiety. A new synthetic route to
      this series of bisphosphate derivatives was introduced, consisting of
      phosphorylation of the pseudoribose moiety prior to coupling with the adenine
      base. The activity of the newly synthesized analogues was determined by measuring
      antagonism of 2-methylthio-ADP-stimulated phospholipase C (PLC) activity in
      1321N1 human astrocytoma cells expressing the recombinant human P2Y(1) receptor
      and by using the radiolabeled antagonist [(3)H]2-chloro-N(6)-methyl-(N)
      methanocarba-2'-deoxyadenosine 3',5'-bisphosphate 5 in a newly developed binding
      assay in Sf9 cell membranes. Within the series of 2-halo analogues, the most
      potent molecule at the hP2Y(1) receptor was an (N)-methanocarba N(6)-methyl-2
      iodo analogue 12, which displayed a K(i) value in competition for binding of
      [(3)H]5 of 0.79 nM and a K(B) value of 1.74 nM for inhibition of PLC. Thus, 12 is
      the most potent antagonist selective for the P2Y(1) receptor yet reported. The 2
      iodo group was substituted with trimethyltin, thus providing a parallel synthetic
      route for the introduction of an iodo group in this high-affinity antagonist. The
      (N)-methanocarba-2-methylthio, 2-methylseleno, 2-hexyl, 2-(1-hexenyl), and 2-(1
      hexynyl) analogues bound less well, exhibiting micromolar affinity at P2Y(1)
      receptors. An enzymatic method of synthesis of the 3',5'-bisphosphate from the
      corresponding 3'-monophosphate, suitable for the preparation of a
      radiophosphorylated analogue, was explored.

PMID- 14584951
TI  - Anti-herpes simplex virus activity of substituted 1-hydroxyacridones.
AB  - 5-Chloro-1,3-dihydroxyacridone, 1, is a potent and selective inhibitor of Herpes
      Simplex Virus Type-1 (HSV-1).(1) Substituted 1,3-dihydroxyacridones represent a
      new class of nonnucleoside HSV-1 inhibitors, and biochemical studies indicate a
      novel mechanism of action for 1, although the target is not yet defined.(2) With
      the goal of lead optimization, analogues of 1 were synthesized in an effort to
      describe the structure-activity relationships between 1 and its hypothetical
      binding site. Modifications of key functional groups led to the identity of
      several features of 1 that were important for activity. In the process, a more
      expedient and reliable synthesis of 1 and its analogues was developed. Analogues
      were evaluated against HSV-1 and HSV-2 using a viral plaque-elimination assay for
      viral inhibition of HSV-1 and HSV-2, and effects on replication of the host cell
      were also measured in order to assess a therapeutic index (TI) of selectivity.
      Several new analogues with significant antiviral activity were identified,
      including 5-methoxy-1,3-dihydroxyacridone (11), which inhibits replication of
      several HSV-2 strains with a mean ED(50) of 0.7 muM and a TI range of 25-60-fold.

PMID- 14584952
TI  - Poly(ethylene glycol) transport forms of vancomycin: a long-lived continuous
      release delivery system.
AB  - The facile reaction of vancomycin with various PEG linkers, at the V(3) position,
      has been selectively accomplished by using an excess of base in DMF. Using rPEG
      as a blocking group for V(3) provides crystalline derivatives that can be further
      PEGylated to give pure V(3)-X(1) latentiated species (transport forms). V(3)
      tetrameric species were also prepared in order to increase the loading of drug on
      PEG. All PEG-vancomycin transport forms show significant antibacterial activity
      that is on the same order of native vancomycin. Significant increases in the AUC
      were observed for all PEG-vancomycin conjugates thus making them potential single
      dose therapies.

PMID- 14584953
TI  - CpG oligonucleotides with modified termini and nicked dumbbell structure show
      enhanced immunostimulatory activity.
AB  - A series of 21 phosphodiester oligodeoxyribonucleotides containing the core
      sequence 5'-GACGTT-3' or related control sequences were prepared and tested for
      their immunostimulatory effect on murine macrophages. The range of structural
      modifications tested included substituents at 3'- or 5'-termini, N3-methylation
      of thymidine residues, and hexaethylene glycol linkers favoring nicked or cyclic
      dumbbell duplexes. Lipophilic and cationic substituents at the termini failed to
      increase the release of TNF-alpha and nitric oxide, but two new types of
      modification were found that enhance the stimulation of RAW264.7 macrophages. One
      is the substitution of the 5'-terminal hydroxyl group with an amino group, and
      the other is the introduction of linkers favoring nicked duplexes. Even for
      sequences without linkers, UV-melting analysis and two-dimensional NMR showed
      that the core sequence 5'-GACGTT-3' readily forms a duplex. The cyclic derivative
      of the most active nicked dumbbell sequence is inactive, however. Together these
      results suggest a recognition of both the 5'-terminus and the core of the CpG
      oligonucleotides by the putative receptor(s) and provide an entry into a class of
      modified oligonucleotides whose activity rivals that of phosphorothioates, but
      consists of synthetic compounds that are single stereoisomers.

PMID- 14584954
TI  - Synthesis and biological evaluation of 5-substituted derivatives of the potent
      antiherpes agent (north)-methanocarbathymine.
AB  - The conformationally locked nucleoside, (north)-methanocarbathymine (1a), is a
      potent and selective anti-herpes agent effective against herpes simplex type 1
      (HSV1) and type 2 (HSV2) viruses. Hereby, we report on the synthesis and
      biological evaluation of a small set of 5-substituted pyrimidine nucleosides
      belonging to the same class of bicyclo[3.1.0]hexane nucleosides. Both the 5
      bromovinyl (4) and the 5-bromo analogue (3) appeared to be exclusive substrates
      of HSV1 thymidine kinase (TK), contrasting with the 5-iodo analogue (2), which
      was significantly phosphorylated by the human cytosolic TK. The binding affinity
      constant and catalytic turnover for HSV1 TK were measured to assess the influence
      of the substitution on these parameters. In the plaque reduction and cytotoxicity
      assays, the 5-bromo analogue (3) showed good activity against HSV1 and HSV2 with
      less general toxicity than 1a. Against varicella-zoster virus (VZV), the north
      locked 5-bromovinyl analogue (4) proved to be as potent as its conformationally
      unlocked 2'-deoxyriboside equivalent BVDU. The three compounds were also tested
      in vitro as prodrugs used in a gene therapy context on three osteosarcoma cell
      lines, either deficient in TK (TK(-)), nontransduced, or stably transduced with
      HSV1 TK. The 5-iodo compound (2, CC(50) 25 +/- 7 microM) was more efficient than
      ganciclovir (GCV, CC(50) 75 +/- 35 microM) in inhibiting growth of HSV1-TK
      transfected cells and less inhibitory than GCV toward TK(-) cells, whereas
      compound 3 inhibited transfected and nontransfected cell lines in a relatively
      similar dose-dependent manner.

PMID- 14584955
TI  - A new generation of N-aryl-N'-(1-alkyl-2-chloroethyl)ureas as microtubule
      disrupters: synthesis, antiproliferative activity, and beta-tubulin alkylation
      kinetics.
AB  - New N-aryl-N'-2-chloroethylureas (CEUs) with enhanced cytotoxicity were developed
      as antimitotic agents potentially useful in cancer chemotherapy. Highly potent
      CEUs were obtained by introduction of a branched alkylating chain, the N'-(1
      methyl-2-chloro)ethyl group. Their cytotoxic activity was enantio-dependent and
      induced through specific alkylation of beta-tubulin, leading to microtubule
      disruption and mitotic arrest. Overall, the structural modifications of the CEUs
      described here significantly improved their kinetics of beta-tubulin alkylation.
      In this new series, CEUs 16a and 18a displayed particularly enhanced
      antiproliferative activity related to a faster reaction with beta-tubulin and
      merit further investigation as potential antitumor agents.

PMID- 14584956
TI  - 5-Substituted-2,4-diamino-6-[2-(phosphonomethoxy)ethoxy]pyrimidines-acyclic
      nucleoside phosphonate analogues with antiviral activity.
AB  - 2,4-Diamino-6-hydroxypyrimidines substituted in position 5 by an allyl, benzyl,
      cyanomethyl, ethoxycarbonylmethyl, phenyl, cyclopropyl, or methyl group were
      prepared either by C5-alkylation or by formation of the pyrimidine ring by
      cyclization. Their alkylation with 2-[(diisopropoxyphosphoryl)methoxy]ethyl
      tosylate afforded N1- and O6-regioisomers that were separated and converted to
      the free phosphonic acids by treatment with bromotrimethylsilane followed by
      hydrolysis. Reaction of 2,4-diamino-6
      [[(diisopropoxyphosphoryl)methoxy]ethoxy]pyrimidine with elemental bromine, N
      chloro-, or N-iodosuccinimide gave the corresponding phosphorus-protected 5-bromo
      , 5-chloro-, and 5-iodo derivatives, respectively. Their deprotection afforded
      2,4-diamino-5-bromo- and -5-chloro-6-[2-(phosphonomethoxy)ethoxy]pyrimidines. 2,4
      Diamino-5-methyl-6-[2-(phosphonomethoxy)ethoxy]pyrimidine was synthesized also by
      cross-coupling of the 5-bromo compound with AlMe(3), followed by deprotection.
      The compounds showed poor, if any, inhibitory activity against DNA viruses such
      as herpes simplex virus type 1 and type 2, cytomegalovirus, varicella-zoster
      virus, and vaccinia virus. In contrast, several 5-substituted 2,4
      diaminopyrimidine derivatives markedly inhibited retrovirus replication in cell
      culture. The 5-methyl derivative was exquisitely inhibitory to human
      immunodeficiency virus and Moloney murine sarcoma virus-induced cytopathicity in
      cell culture (EC(50) approximately 0.00018 mumol/mL) but also cytostatic to CEM
      cell cultures. In contrast, the 5-halogen-substituted derivatives showed
      pronounced antiretroviral activity (EC(50) = 0.0023-0.0110 mumol/mL), comparable
      to that of the reference drugs adefovir and tenofovir, but were devoid of
      measurable toxicity at 0.3 mumol/mL.

PMID- 14584957
TI  - Synthesis and biological evaluation of 2,4-diamino-6-(arylaminomethyl)pyrido[2,3
      d]pyrimidines as inhibitors of Pneumocystis carinii and Toxoplasma gondii
      dihydrofolate reductase and as antiopportunistic infection and antitumor agents.
AB  - A series of 2,4-diamino-6-(arylaminomethyl)pyrido[2,3-d]pyrimidines were
      synthesized and evaluated as inhibitors of Pneumocystis carinii (pc), Toxoplasma
      gondii (tg), and rat liver (rl) dihydrofolate reductase (DHFR) and as inhibitors
      of the growth of tumor cell lines in culture. Compounds 4-15 were designed as
      part of a continuing effort to examine the effects of substitutions at the 5
      position, in the two-atom bridge, and in the side chain phenyl ring on structure
      activity/selectivity relationships of 2,4-diaminopyrido[2,3-d]pyrimidines against
      a variety of DHFRs. Reductive amination of the common intermediate 2,4
      diaminopyrido[2,3-d]pyrimidine-6-carbonitrile 16 with the appropriate anilines
      afforded the target compounds 4-12. Nucleophilic substitution or reductive
      methylation afforded the N10-methyl target compounds 13-15. As predicted,
      compounds 4-15 were, in general, less potent against all three DHFRs compared to
      the corresponding 2,4-diamino-5-methyl analogues previously reported; however,
      the greater decrease in potency against rlDHFR compared to pcDHFR and tgDHFR
      resulted in appreciable selectivity toward pathogenic DHFRs from different
      pathogens. The 2',5'-dichloro analogue 8 showed selectivity ratios (IC(50)
      against rlDHFR/IC(50) against pcDHFR or tgDHFR) of 15.7 and 23 for pcDHFR and
      tgDHFR, respectively. Thus, the selectivity of 8 for pcDHFR is higher than the
      first line clinical agent trimethoprim (TMP). In a P. carinii cell culture study,
      analogue 8 exhibited 88% cell growth inhibition at a concentration of 10 muM and
      afforded marginal effects in an in vivo study in the T. gondii mouse model.
      Selected compounds were evaluated in the National Cancer Institute (NCI) in vitro
      preclinical antitumor screening program and inhibited the growth of tumor cells
      in culture at micromolar to submicromolar concentrations and were selected for
      evaluation in a NCI in vivo hollow fiber assay.

PMID- 14584959
TI  - Molecular docking studies of natural cholinesterase-inhibiting steroidal
      alkaloids from Sarcococca saligna.
AB  - Alkaloids isolated from Sarcococca saligna significantly inhibit acetyl- and
      butyrylcholinesterase enzyme, suggesting discovery of inhibitors for nervous
      system disorders. Studying interactions with the active site of the AChE enzyme
      from Torpedo californica, we have identified hydrophobic interactions inside the
      aromatic gorge area as the major stabilizing factor in enzyme-inhibitor complexes
      of these alkaloids. Molecular Dynamics simulation of a predicted complex
      indicates that ligand binding does not extensively alter enzyme structure, but
      reduces flexibility at the gorge.

PMID- 14584958
TI  - Synthesis, in vitro evaluation, and intraocular pressure effects of water-soluble
      prodrugs of endocannabinoid noladin ether.
AB  - The poor aqueous solubility of 2-arachidonyl glyceryl ether (noladin ether) 2
      hinders both pharmacological studies and pharmaceutical development. The
      synthesized mono- and diphosphate esters of noladin ether (4 and 6) considerably
      increased the aqueous solubility of noladin ether (>40000-fold), showed high
      stability against chemical hydrolysis in buffer solutions, and were rapidly
      converted to the parent drug via enzymatic hydrolysis. The monophosphate ester of
      noladin ether reduced intraocular pressure in normotensive rabbits.

PMID- 14584960
TI  - Estrogenic potential of 2-alkyl-4-(thio)chromenone 6-O-sulfamates: potent
      inhibitors of human steroid sulfatase.
AB  - 2-Alkylchromen-4-one 6-O-sulfamates, a new class of potent steroid sulfatase
      (STS) inhibitors, were evaluated for their estrogenic potential. Structure
      activity relationships for estrogenic activity were identified; however, no
      correlation with STS inhibition was found. Estrogenicity is favored by bulky side
      chains and can be effectively abrogated by an (additional) linear substituent.
      Compound 2g, which lacks estrogenicity while potently inhibiting STS, has an
      ideal in vitro profile for the treatment of breast cancer.

PMID- 14584961
TI  - Tissue storage of 14C-labelled hydroxyethyl starch (HES) 130/0.4 and HES 200/0.5
      after repeated intravenous administration to rats.
AB  - OBJECTIVE: To investigate the effect of the molar substitution of hydroxyethyl
      starch (HES) solutions on tissue and organ storage in rats after repeated
      administration. STUDY DESIGN: A controlled, multiple-dose study was performed in
      48 rats. Daily bolus injections of 0.7 g/kg of 10% HES 130/0.4 or 10% HES 200/0.5
      were administered on 18 consecutive days. In order to examine quantitatively the
      distribution and excretion of both preparations on HES tissue storage,
      radiolabelled HES was measured 3, 10, 24 and 52 days after the last
      administration. Tissue storage was expressed as percentage radioactivity of total
      administered HES dose in the total body, carcass, liver, kidney, spleen, lymph
      nodes, plasma and urine. RESULTS: 52 days after the last administration the
      remaining radioactivity of labelled HES 200/0.5 was nearly 4-fold higher compared
      with HES 130/0.4 in the total body (2.45% vs 0.65% of the total administered
      dose). This difference in tissue storage was statistically significant (p < or =
      0.01). A comparable difference was observed for the liver and carcass.
      CONCLUSION: Tissue storage after repeated administration of an HES solution with
      a low molar substitution (0.4) was significantly lower in the total body as well
      as in the liver and carcass compared with an HES solution with a medium molar
      substitution (0.5). However, the potential clinical consequences of these present
      findings have not yet been determined.

PMID- 14584962
TI  - Pharmacokinetics of deramciclane, a novel anxiolytic agent, after intravenous and
      oral administration.
AB  - BACKGROUND AND OBJECTIVE: Deramciclane is a new compound that has shown
      anxiolytic effects in animal experiments and in human studies. The aim of this
      study was to determine the pharmacokinetic parameters of deramciclane after
      intravenous and oral administration, and its oral bioavailability. METHODS:
      Deramciclane 30 mg was given intravenously and orally as a tablet and as solution
      in an open, randomised, crossover three-period trial to 12 healthy male
      volunteers. Oral bioavailability of deramciclane and the pharmacokinetic
      parameters of deramciclane and N-desmethylderamciclane, the principal metabolite,
      were determined after intravenous and oral administration of the parent drug.
      RESULTS: The first and second distribution half-lives (mean +/- SD) of
      deramciclane were 0.04 +/- 0.01 and 3.03 +/- 0.50h, respectively, and the half
      life of the elimination phase was 26.6 +/- 5.5h. The clearance of deramciclane
      after an intravenous dose was 0.24 +/- 0.10 L/kg. The elimination phase half-life
      of N-desmethylderamciclane was 38.2 +/- 6.9h after intravenous and about 25 h
      after oral dosing of the parent compound. The mean oral bioavailability of
      deramciclane was 44% (range 27-58%) and 36% (23-50%) after administration of the
      oral solution and tablet, respectively. Deramciclane was well tolerated even
      after a 30 mg intravenous dose resulting in peak plasma concentrations 10 times
      higher than observed after its oral administration. CONCLUSIONS: After
      intravenous administration, the pharmacokinetics of deramciclane are adequately
      described by a three-compartment model. After oral administration its
      pharmacokinetics follow a two-compartment model with first-order absorption. The
      elimination phase half-life of the parent compound is similar after intravenous
      and oral administration, whereas the apparent half-life of N
      desmethylderamciclane is longer after intravenous than after oral administration
      of the parent compound. The oral bioavailability of deramciclane is large and
      uniform enough to allow its clinical use as tablets.

PMID- 14584963
TI  - Cinacalcet: AMG 073, Calcimimetics--Amgen/NPS Pharmaceuticals, KRN 1493, NPS
      1493.
AB  - Cinacalcet [AMG 073, KRN 1493, NPS 1493] is an orally active, second-generation
      calcimimetic compound licensed by NPS Pharmaceuticals to Amgen in the US for
      potential treatment of hyperparathyroidism (HPT). Cinacalcet modulates (increases
      the sensitivity of) calcium receptors on the surface of parathyroid cells thereby
      inhibiting the oversecretion of parathyroid hormone, which characterises HPT. It
      also represents a potentially significant advance for chronic kidney disease
      patients diagnosed with secondary HPT, a common yet serious metabolic disorder
      where parathyroid hormone levels are elevated. Patients with this disease can
      suffer from bone disease, bone pain and fractures, soft tissue calcification,
      vascular calcification and cardiovascular complications. Amgen has rights to
      develop and sell cinacalcet throughout the world except in Japan, Taiwan and
      China, where the compound was licensed to Kirin Brewery. Kirin is developing it
      as KRN 1493 in phase II clinical studies in Japan. In December 2001, commencement
      of a phase III clinical trial with cinacalcet for the treatment of secondary HPT,
      triggered a 3 million US dollars milestone payment to NPS Pharmaceuticals. In
      September 2003, submission of an NDA to the US FDA for cinacalcet for secondary
      HPT will be followed by a milestone payment of 6 million US dollars to NPS. NPS,
      Kirin and Amgen were also developing another compound, tecalcet, for HPT, but
      that project has been discontinued in favour of cinacalcet. In September 2003,
      Amgen submitted an NDA to the US FDA for secondary HPT in patients with chronic
      kidney disease. In April 2003, Amgen announced positive results from a phase III
      clinical trial with cinacalcet in patients with secondary HPT. In a clinical
      study in patients on dialysis suffering from the effects of chronically elevated
      levels parathyroid hormone, cinacalcet appeared to be safe and well tolerated and
      was significantly more effective than placebo. Two more additional efficacy
      studies with cinacalcet have also been completed. Phase II trials of cinacalcet
      in dialysis patients with secondary HPT and in patients with primary HPT were
      successfully completed.

PMID- 14584964
TI  - Decitabine: 2'-deoxy-5-azacytidine, Aza dC, DAC, dezocitidine, NSC 127716.
AB  - Decitabine [NSC 127716, DAC, dezocitidine, Aza dC, 2'-deoxy-5-azacytidine,
      Dacogen( trade mark )] is a deoxycytidine and cytarabine derivative with potent
      antileukaemic activity, originated by Pharmachemie. This antimetabolite is able
      to induce in vitro gene activation and cellular differentiation by a mechanism
      involving DNA hypomethylation. Decitabine has been studied in several phase II
      trials for solid tumours as well as in different types of leukaemia. The drug has
      been shown to have very limited efficacy against solid tumours. However,
      decitabine exhibits higher activity for the treatment of haematological
      malignancies. SuperGen announced that it had entered a Cooperative Research and
      Development Agreement (CRADA) with the US National Cancer Institute (NCI) in May
      2000. SuperGen will supply decitabine to the NCI, which will initiate and sponsor
      clinical trials in patients with solid tumours and haematological malignancies.
      The NCI will also conduct studies on decitabine's mechanism of action. SuperGen
      had previously acquired worldwide rights to decitabine from Pharmachemie in the
      third quarter of 1999 for 4 million US dollars worth of SuperGen shares and
      income from manufacture upon the launch of decitabine. The drug is undergoing two
      phase II trials for the treatment of cytomegalovirus leukaemia (CML) in the US,
      one of which will assess the safety, response rate, duration of response, and
      survival of decitabine (injection) in combination with imatinib mesylate (oral).
      SuperGen initiated a phase II clinical study of decitabine in combination with
      imatinib mesylate in June 2003 that will be conducted under SuperGen's CRADA with
      the National Cancer Institute and will take place at the MD Anderson Cancer
      Center in the US. Approximately 80 patients with CML will be enrolled in the
      study. This followed on decitabine's orphan drug status for the same indication,
      which was granted by the US FDA in 2002. In addition, the European Commission has
      granted orphan drug status to decitabine for MDS treatment in February 2003. In
      March 2003, SuperGen announced that patient enrolment was completed for its open
      label, phase III trial comparing decitabine with standard care therapy for
      treatment of advanced myelodysplastic syndrome, which was initiated in March
      2001. The study will be conducted at 22 medical centres in the US and will enrol
      a total of 160 patients. A pivotal trial is also underway in Europe for the same
      indication and is aiming to enrol 220 patients. In addition, decitabine is
      undergoing phase II trials for the treatment of non-small cell lung cancer
      (NSCLC) in Canada and for prostate cancer in the US. In July 2003, SuperGen was
      issued a US patent relating to decitabine as part of a combination therapy with
      other anticancer agents to treat ovarian, breast, prostate, gastric, lung,
      pancreatic and colon cancers through the correction of DNA hypermethylation.
      SuperGen was issued a US patent (No. 6 191 119) in 2001 covering the use of
      decitabine in combination with rubitecan and antibiotic agents, including
      doxorubicin.

PMID- 14584965
TI  - Diquafosol: DE 089, diquafosol tetrasodium, INS 365, INS 365 Ophthalmic, INS 365
      Respiratory, KPY 998.
AB  - Diquafosol [INS 365, KPY 998, diquafosol tetrasodium, DE 089, INS 365
      Respiratory, INS 365 Ophthalmic] is a mucolytic compound that stimulates
      mucociliary clearance and also hydrates the mucosal surface of the lung. It is an
      activator of the P2Y2 receptor, which appears to be a key regulator of
      mucociliary clearance. Unlike the earlier P2Y2 receptor agonists such as uridine
      5'-triphosphate, diquafosol is very stable chemically and does not require
      refrigeration or special handling. This makes diquafosol suitable for the
      treatment of chronic conditions. Diquafosol was originally developed at the
      University of North Carolina in the US. In September 2003, the US FDA announced
      that it accepted Inspire Pharmaceuticals' NDA filing for diquafosol tetrasodium
      ophthalmic solution for the treatment of dry eye. Additionally, FDA has completed
      a preliminary review of the NDA and issued the Filing Review Letter stating that
      no potential filing review issues were found during the review period. Inspire
      Pharmaceuticals' NDA for diquafosol has been granted priority review status, with
      initial FDA action expected at a target of 6 months after NDA submission. The
      first launch of diquafosol could potentially occur in the first quarter of 2004.
      Previously in January 2002, preliminary results from one of the US trials (study
      104) revealed that the primary efficacy objectives of the study were not met.
      Data were re-evaluated and resubmitted in March 2002. Inspire Pharmaceuticals
      received a milestone payment from Allergan, which was not dependent on the study
      outcome, following the completion of study 104 and the submission of these study
      data. Phase II trials of diquafosol for dry eye are being conducted in Japan by
      Santen Pharmaceuticals. Santen projects that the compound will be launched in
      Japan during 2008-9. Phase I trials are also being conducted in the UK.
      Diquafosol eye drops activate P2Y2 receptors on the surface of the eye and inner
      eyelids, enhancing the natural process of tear secretion. Stimulation of tear
      secretion with diquafosol causes the release of salt, water, mucin and other
      components of the tear film, resulting in hydration of the surface of the eye. As
      there are no approved pharmacological therapies for dry eye, diquafosol is a
      potential breakthrough treatment for this disorder.

PMID- 14584966
TI  - Doripenem: S 4661.
AB  - Doripenem [S 4661] is a new parenteral carbapenem antibacterial undergoing
      clinical trials in Japan and North America. It is characterised by a 1beta-methyl
      group and a sulfamoylaminomethyl substituted pyrrolidylthio group at the C2
      position. The compound has good activity against both Gram-positive and Gram
      negative bacteria and superior activity to meropenem and imipenem against
      Pseudomonas aeruginosa. It possesses higher stability than imipenem or meropenem
      against animal dehydropeptidase I. The compound is stable to most beta-lactamases
      produced by Gram-negative bacteria. Shionogi has stated that doripenem is
      expected to be effective at low doses. In May 2003, Shionogi and Peninsula
      Pharmaceuticals (USA) entered a licensing agreement for doripenem under which
      Peninsula obtained exclusive rights (including sublicense rights) to market and
      develop the product in North America. Shionogi will manufacture doripenem for
      worldwide distribution. Doripenem is currently undergoing phase III trials in
      Japan for pneumonia, chronic respiratory tract infections (RTIs) and urinary
      tract infections (UTIs). In its November 2002 pipeline, Shionogi stated that it
      plans to file a NDA in Q4 of 2003. Doripenem is also in phase II studies in
      hospitalised patients with complicated urinary tract infections including
      pyelonephritis. In September 2003, Peninsula announced it had completed enrolment
      in this trial, and results are expected later in the year. Doripenem has also
      completed two phase I studies in healthy volunteers with a number of different
      dosing regimens.

PMID- 14584967
TI  - Factor VIII--Baxter: rAHF-PFM, recombinant anti-haemophilic factor--protein-free
      method, recombinant factor VIII--protein-free.
AB  - Baxter Healthcare is developing a next-generation recombinant factor VIII for the
      treatment of haemophilia A that is produced using a totally protein-free
      manufacturing process. By excluding proteins or raw materials derived from human
      or animal sources in the final product, the risk of transmission of potentially
      infectious agents is removed. All of the recombinant factor VIII products
      currently on the market incorporate proteins or raw materials derived from either
      human or animal sources, as part of the nutrients required for the cells to
      produce the protein. Baxter has exclusive rights to Quadrant Healthcare's factor
      VIII stabilisation technology. Quadrant received 1 million US dollars under the
      agreement, and was to receive milestone payments in excess of 2 million US
      dollars, together with royalties on sales should a new factor VIII product using
      Quadrant's technology reach the market. In December 2000, Quadrant Healthcare was
      acquired by Elan Drug Delivery (Elan Corporation), which continued to develop the
      proprietary formulation and stabilisation technologies of Quadrant. In July 2003,
      the newly formed company Quadrant Technologies acquired Elan Drug Delivery from
      Elan Corporation and renamed it Quadrant Drug Delivery. In July 2003, the US FDA
      approved the use of ADVATE for the prevention and control of bleeding episodes in
      people with haemophilia A. At the Bear Stearns 16th Annual Healthcare Conference
      held in September 2003, Baxter reported that ADVATE was launched in August 2003
      in the US. A pivotal phase III clinical trial of this recombinant factor VIII
      therapy, initiated in 89 previously untreated patients with haemophilia A, has
      been completed at sites in the US, UK, Sweden, France, Belgium, Germany, Denmark
      and Italy. This trial compared the pharmacokinetics, tolerability and
      immunogenicity of this therapy with Baxter's currently marketed recombinant
      factor VIII preparation, Recombinate trade mark. The first clinical data that
      were presented on this agent at the XXV International Congress of the World
      Federation of Hemophilia meeting indicate that Baxter's next-generation
      recombinant factor VIII is bioequivalant with Recombinate trade mark. The two
      agents should have comparable efficacy. A Marketing Authorisation Application
      (MAA) was submitted to the EU EMEA and regulatory filings were made in Canada in
      September 2002. The submission was made via the centralised procedure. Should the
      new-generation product reach the market, Baxter will continue to offer
      Recombinate trade mark as well as plasma-derived factor VIII products.
      Preliminary study results announced in July 2003 show that factor VIII therapy
      was effective in controlling bleeding episodes in patients with severe and
      moderately severe haemophilia A who were previously treated, or had undergone
      surgery.

PMID- 14584968
TI  - Lobaplatin: D 19466.
AB  - Lobaplatin [D 19466] is a platinum complex with DNA alkylating activity that was
      developed by ASTA Medica (Degussa) for the treatment of cancer. ASTA Medica
      discontinued development of lobaplatin, and subsequent development of the
      compound became the responsibility of Zentaris AG (AEterna Laboratories), which
      was formed in 2001 from the biopharmaceutical, inhalation technology and gene
      therapy activities of ASTA Medica. On 30 December 2002, Zentaris was acquired by
      AEterna Laboratories. Cisplatin, one of the original platinum compounds, has had
      a major impact on the treatment of solid tumours such as germ cell cancer,
      ovarian cancer, bladder cancer and bronchial carcinoma, but its clinical
      usefulness is limited by renal, neurological and gastrointestinal toxicity. This
      has led to the development of second- and third-generation platinum analogues,
      such as lobaplatin, with reduced toxicity and a better therapeutic index. In
      January 2003, Zentaris AG and Hainan Tianwang International Pharmaceutical signed
      a contract for the manufacture and marketing of lobaplatin in China. The
      technology transfer agreement provides for Zentaris to receive a one-time payment
      to the amount of 4.5 million Canadian dollars. In addition, the contract foresees
      for Tianwang to manufacture and deliver lobaplatin to Zentaris or its partners
      for marketing in all other countries worldwide. Lobaplatin has been approved in
      China for the treatment of chronic myelogenous leukaemia (CML) and inoperable,
      metastatic breast and small cell lung cancer. However, it has not yet been
      launched there. In June 2003, AEterna reported that it expects lobaplatin to be
      launched in China by the end of 2003 at the 10th Annual Meeting of the
      Biotechnology Industry Organization (BIO-2003). Lobaplatin has also completed
      phase II clinical trials in the US, Australia, EU, Brazil and South Africa for
      the treatment of various cancers, including breast, oesophageal, lung and ovarian
      cancers as well as CML.

PMID- 14584969
TI  - Morphine Liposomal--SkyePharma: C 0401, D 0401, morphine--DepoFoam, SKY 0401.
AB  - The SkyePharma PLC subsidiary SkyePharma Inc. (formerly DepoTech) is developing a
      sustained-release formulation of morphine sulphate [DepoMorphine, C 0401, D 0401,
      SKY 0401] using its DepoFoam proprietary drug delivery technology. It is intended
      for epidural administration in the treatment of acute postoperative pain.
      DepoFoam consists of microscopic spherical particles with internal aqueous
      chambers separated by lipid membranes containing the encapsulated drug. DepoFoam
      particles are synthetic replicas of natural lipids that are biodegradable and
      biocompatible. DepoFoam can be administered subcutaneously, intramuscularly and
      intrathecally. In December 2002, SkyePharma and Endo Pharmaceuticals signed a
      development and commercialisation agreement providing Endo Pharmaceuticals with
      exclusive marketing and distribution rights in the US and Canada for Depomorphine
      and another product, Propofol IDD-D trade mark, with options for other
      development products. Under the terms of the agreement, SkyePharma will receive
      an upfront payment and may receive further milestone payments. Skye-Pharma will
      also receive a share of each product's sales revenue. SkyePharma is responsible
      for clinical development towards the US FDA approval and for product manufacture
      and associated costs. Following the approval, SkyePharma will as act as a
      supplier, while Endo will market each product in the US and Canada. SkyePharma
      has received 30 million US dollars from Paul Capital Partners, a US private
      equity group, to develop DepoMorphine. This capital will enable SkyePharma to
      fund phase III clinical trials without raising extra funds. Paul Capital will
      have rights to 15% of any revenues from DepoMorphine until 2014, and also receive
      some royalties on three other SkyePharma products. However, if DepoMorphine fails
      in clinical trials or is declined for registration, Paul Capital will not be
      compensated for the investment. SkyePharma expect to conclude a European license
      by the end of 2003, and are also in discussions with potential Japanese
      licensees. In July 2003, SkyePharma submitted an NDA to the US FDA for
      DepoMorphine in the treatment of moderate to severe postoperative pain. The FDA
      accepted the filing in September, triggering a milestone payment to Skye-Pharma.
      Positive results from two phase III trials in 750 patients after hip surgery and
      lower abdominal surgery released in June 2003 report that DepoMorphine is
      effective in providing sustained dose-related analgesia. DepoMorphine
      demonstrated sustained dose-related analgesia and achieved its primary endpoint
      and also statistical significance on several secondary endpoints such as patient
      perception of pain intensity and adequacy of pain relief. The Financial Times in
      January 2001 reported that analysts have forecast DepoMorphine to reach peak
      sales of more than 200 million US dollars. In April 2001, the Wall Street Journal
      quoted the CEO of SkyePharma predicting that DepoMorphine has the potential to
      reach combined annual sales, in the US and Europe, of approximately 350 million
      US dollars.

PMID- 14584970
TI  - MT 300--POZEN: dihydroergotamine mesylate injection.
AB  - MT 300 is an injectable formulation of dihydroergotamine mesylate (DHE; a
      serotonin 5-HT1 receptor agonist) that is being developed by POZEN for the acute
      treatment of migraine. POZEN intends to present MT 300 as a prefilled syringe
      that can be administered alone, or with an autoinjector. In September 2003, POZEN
      announced that it had formed a commercialisation agreement with Xcel
      Pharmaceuticals. Under the terms of the agreement Xcel will have exclusive rights
      to commercialise MT 300 in the United States, and will pay POZEN upfront and
      milestone payments, as well as royalties on future sales. In December 2002, POZEN
      submitted an NDA to the US FDA for MT 300 for the acute treatment of migraine
      with or without aura. In March 2003 POZEN announced that its New Drug Application
      (NDA) for MT 300 had been accepted for filing by the US FDA. Two phase III trials
      have been completed in the US. Both studies, the first involving 619 patients
      with migraine and the second (and final study) involving 550 patients with
      migraine, have produced promising results. POZEN received a US patent (6,495,535)
      with claims related to therapeutic packaging of dyhydroergotamine in a prefilled
      syringe. This is the first issued patent for MT 300. POZEN has multiple pending
      foreign patent applications. The patents have claims regarding liquid
      pharmaceutical compositions for the treatment of migraine, which contain
      concentrated dihydroergotamine.

PMID- 14584971
TI  - Petasites--Zeller: ZE 339.
AB  - The Swiss company Zeller is developing an extract of the plant Petasites hybridus
      (butterbur) as an antiallergic agent. Petasites hybridus extracts have been known
      for some time to have therapeutic properties. Zeller's extract is codenamed ZE
      339. In in vitro studies, ZE 339 inhibited cysteinyl-leukotriene synthesis in
      eosinophils and leukotriene B4 synthesis in neutrophils. In mid-2003, ZE 339 was
      approved, and launched, in Switzerland as Tesalin for the treatment of seasonal
      allergic rhinitis as a prescription-only product. Tesalin is available as film
      coated tablets. Zeller has stated that hepatotoxicity cannot be totally excluded
      as a possible adverse reaction to Tesalin.

PMID- 14584972
TI  - SR 58611A: SR 58611.
AB  - SR 58611A [SR 58611], a highly selective agonist for atypical beta3
      adrenoceptors, inhibits intestinal motility. This (phenylethanol) aminotetraline
      sympathomimetic was originated by Sanofi as a potential treatment for irritable
      bowel syndrome but is now in development for depression. SR 58611A is currently
      in phase III trials for depression in France. A phase IIa trial of SR 58611A in
      patients with severe recurrent depression showed it to be superior to fluoxetine
      and well tolerated, while a phase IIb trial demonstrated comparable efficacy and
      tolerability to paroxetine. SR 58611A was in phase II clinical trials in France
      for irritable bowel syndrome but there is no record of active development of SR
      58611A for this indication. SR 58611A had also been in phase IIa for the
      treatment of obesity but no recent development has been reported for this
      indication. SR 58878 is the acid metabolite of SR 58611A.

PMID- 14584973
TI  - Staphylococcus aureus vaccine conjugate--Nabi: Nabi-StaphVAX, StaphVAX.
AB  - Staphylococcus aureus is a major cause of hospital-acquired infections and
      infections in kidney dialysis patients. Over 90% of these infections are due to
      types 5 and 8. Nabi, under a CRADA agreement with the US National Institutes of
      Health, is developing a bivalent vaccine against S. aureus types 5 and 8 [Nabi
      StaphVAX, StaphVAX]. The vaccine contains type 5 and type 8 S. aureus capsular
      polysaccharides conjugated to a protein carrier (recombinant exoprotein A, a
      genetically detoxified form of Pseudomonas aeruginosa exotoxin A). Nabi changed
      its name to Nabi Biopharmaceuticals on 5 March 2002. StaphVAX is available for
      licensing (http://www.nabi.com). Nabi's preference is for a licensee that can
      provide non-US marketing and regulatory capabilities in addition to financial
      resources to accelerate the vaccine's development. Nabi intends to develop a
      second-generation version of StaphVAX that will include antigen from
      Staphylococcus type 336. This would increase the vaccine's coverage of
      staphylococcal infection. Nabi also intends to develop two combination vaccines.
      The first, StaphVAX+ will contain both StaphVAX and EpiVAX trade mark in a single
      vial and the second, CombiVAX, will contain components of StaphVAX, EpiVAX trade
      mark and EnteroVAX trade mark. The vaccine has completed phase II clinical trials
      in chronic, ambulatory, peritoneal dialysis patients. Nabi-StaphVAX completed a
      multicentre, phase III trial in the US involving 1800 end-stage renal disease
      patients on haemodialysis. In September 2000, Nabi announced preliminary results
      from the phase III trial; these indicated that although Nabi-StaphVAX elicited a
      significant decrease in S. aureus bacteraemias in the first 10 months after
      vaccination, statistical significance was not reached in the primary endpoint of
      the study, a decrease after 1-year follow up. As a result, the US FDA indicated
      that US registration would require a second phase III trial in which the primary
      endpoint is reached. Following discussions with the US FDA, Nabi stated that the
      initiation of a second phase III trial in collaboration with a corporate partner
      was likely. Nabi intends to request either an accelerated- or fast-track review
      by the FDA, on the basis that the vaccine prevents a fatal disease for which no
      other prophylactics are available. In the meantime, Nabi initiated a boosting
      study of Nabi-StaphVAX in July 2001. This trial is administering a second dose of
      Nabi-StaphVAX to 100 patients enrolled in the phase III trial. Nabi plans to
      begin the confirmatory phase III study of the vaccine, as requested by the US
      FDA, in 3000 end-stage kidney patients in Q4 2003. The primary endpoint will be a
      statistically significant reduction of S. aureus bacteraemia caused by type 5 and
      8 S. aureus through 8 months post-vaccination, the peak efficacy point in the
      first phase III trial. This trial will include a booster vaccination at 8 months
      and vaccinees will be followed up for up to 6 months after the booster to
      evaluate the vaccine's ability to generate antibodies, efficacy and safety.
      Results from this study will be used to support eventual product registration,
      now planned for 2005. In July 2003, Nabi reported that proceeds totalling 32.9
      million US dollars from the private placement of its common stock to selected
      investors will enable the planned confirmatory phase III trial to proceed. In
      June 2003, Nabi Biopharmaceuticals announced the start of a clinical trial (a
      bridging study) to evaluate the safety and immunogenicity of a newly manufactured
      lot of StaphVAX produced by the contract manufacturer, Dow Biopharmaceutical
      Contract Manufacturing, intended for use in a planned confirmatory phase III
      trial later in 2003. The study demonstrated that the new batch of vaccine
      generated antibody levels that were equivalent to the levels generated by the
      vaccine produced at Nabi's R&D pilot plant and used in previous phase III
      studies.

PMID- 14584974
TI  - Xaliproden: SR 57746, SR 57746A, xaliproden hydrochloride, xaliprodene.
AB  - Xaliproden [SR 57746A, xaliprodene; Xaprila] is a compound that mimics the
      effects of nerve growth factor and is also a serotonin 5-HT1A receptor agonist.
      The drug was originated by Sanofi, and in mid-1999, Sanofi merged with Synthelabo
      to form Sanofi-Synthelabo. Phase III trials have been completed in patients with
      amyotrophic lateral sclerosis in Europe, the US and Canada. Xaliproden is at the
      phase II stage of clinical development for amyotrophic lateral sclerosis in
      Japan, where it also has orphan drug status for this indication.

PMID- 14584975
TI  - Xemilofiban: SC 54684A, xemlofiban.
AB  - Xemilofiban [SC 54684, SC 54684A (HCl), xemlofiban], a glycoprotein IIb/IIIa
      antagonist, is an orally available prodrug of a non-peptide mimetic of the
      tetrapeptide RGDF. It is converted to the active metabolite, SC 54701 (the free
      base form of SC 54701A). Development was initiated by Searle (Monsanto). Searle
      became part of Pharmacia Corporation, which was acquired by, and merged into,
      Pfizer in April 2003. Searle had co-development and co-marketing agreements with
      Sankyo in Japan; these have been discontinued. In January 2003, Pharmacia donated
      the intellectual property for xemilofiban to Western Michigan University. In
      February 2003, Western Michigan University granted an exclusive worldwide licence
      of xemilofiban to VDDI Pharmaceuticals (formerly Virtual Drug Development Inc.).
      Xemilofiban was in a phase III clinical trial, the Evaluation of Xemilofiban in
      Controlling Thrombotic Events (EXCITE) trial, with Searle (Monsanto) in the US
      and Europe for the treatment of thrombosis in patients with unstable angina
      pectoris and acute myocardial infarction undergoing angioplasty. However, as
      xemilofiban demonstrated no significant clinical benefit, Searle discontinued its
      development. In Japan, Sankyo discontinued the development of xemilofiban for
      thrombosis at phase II following Searle's decision to drop the project. VDDI
      Pharmaceuticals plans to develop xemilofiban in cardiovascular disorders
      following on from the phase III studies completed by Pharmacia; a restructured
      dosing schedule and narrowed patient selection will be used. VDDI has research
      facilities worldwide and will utilise facilities in Ireland for the European
      clinical development programme; research facilities in the Southwest Michigan
      Innovation Center are planned while the head office of VDDI is based in
      Tennessee. Xemilofiban is in phase III development for the treatment of
      cardiovascular disease in conjunction with percutaneous coronary intervention.

PMID- 14584976
TI  - Does information about what things are influence children's memory for where
      things are?
AB  - Two experiments examined how information about what objects are influences memory
      for where objects are located. Seven-, 9-, and 11-year-old children and adults
      learned the locations of 20 objects marked by dots on the floor of a box. The
      objects belonged to 4 categories. In one condition, objects belonging to the same
      category were located in the same quadrant of the box. In another condition,
      objects and locations were randomly paired. After learning, participants
      attempted to replace the objects without the aid of the dots. Children and adults
      placed the objects in the same quadrant closer together when they were related
      than when they were unrelated, indicating that object information led to
      systematic biases in location memory.

PMID- 14584977
TI  - Maternal power assertion in discipline and moral discourse contexts:
      commonalities, differences, and implications for children's moral conduct and
      cognition.
AB  - Parental power assertion is traditionally studied in the behavioral domain-
      discipline triggered by the child's immediate misbehavior--but rarely in the
      cognitive domain--parent-child discussions of the child's past misbehavior.
      Maternal power assertion was observed in "do" and 'don't" discipline contexts
      from 14 to 45 months and in the context of mother-child discourse about a recent
      misbehavior at 56 months. Mothers' use of power cohered across the "do," 'don't,"
      and discourse contexts, but its implications were domain specific. Power
      assertion in the 'don't" discipline context predicted behavioral outcomes (more
      moral conduct at 56 and 73 months, less antisocial conduct at 73 months) but not
      cognitive outcomes (moral cognition at 56 and 73 months). Power assertion in the
      discourse context predicted less mature moral cognition but not moral or
      antisocial conduct. Mothers' high Neuroticism predicted more power assertion in
      all three contexts. Child effects were examined.

PMID- 14584978
TI  - Reasoning with premises that are not empirically true: evidence for the role of
      inhibition and retrieval.
AB  - Two studies examined conditional reasoning with false premises. In Study 1, 12-
      and 16-year-old adolescents made "if-then" inferences after producing an
      alternative antecedent for the major premise. Older participants made more errors
      on the simple modus ponens inference than did younger ones. Reasoning with a
      false premise reduced this effect. Study 2 examined the relation between
      performance on a negative priming task (S. P. Tipper, 1985) and reasoning with
      contrary-to-fact premises in 9- and 11-year-olds. Overall, there was a
      correlation between the relative effect of negative priming on reaction times and
      the number of knowledge-based responses to the reasoning problems. The results of
      these studies are consistent with the idea that reasoning with premises that are
      not true requires an interaction between information retrieval and inhibition.

PMID- 14584979
TI  - Social regulatory effects of infant nondistress vocalization on maternal
      behavior.
AB  - This study investigated the social regulatory function of infant nondistress
      vocalization in modulating maternal response. Thirteen infants and their mothers
      were observed weekly in a face-to-face interaction situation from 4 to 24 weeks.
      After the occurrences and the speech quality of infant nondistress vocalization
      were identified, maternal contingent responses to these vocalizations were also
      coded. Each responsive action was further classified by the change processes
      involved. Results showed that it was the occurrence of infant nondistress
      vocalization rather than its speech quality that regulated maternal verbal
      response concurrently and that infant nondistress vocalization was more likely to
      be synchronized with maternal facial expression and touch than with head
      movements. Developmentally, significant individual differences were found in the
      linear growth patterns of overall maternal response and within the individual
      modalities when responding to speechlike vocalizations.

PMID- 14584980
TI  - Rejected bullies or popular leaders? The social relations of aggressive subtypes
      of rural african american early adolescents.
AB  - Teacher assessments of interpersonal characteristics were used to identify
      subtypes of rural African American early adolescents (161 boys and 258 girls).
      Teacher ratings of interpersonal characteristics were used to identify popular
      and unpopular aggressive subtypes for both boys and girls. Unpopular aggressive
      youths did not have elevated levels of rejected sociometric status but were more
      likely to have lower levels of peer-perceived social prominence and social
      skills. Conversely, popular aggressive youths were more likely to be disliked by
      peers even though they were perceived by peers as socially prominent and socially
      skilled and were identified by teachers as highly involved in extracurricular
      activities. Both popular and unpopular aggressive youths tended to associate with
      others who had similar levels of peer-perceived popularity.

PMID- 14584981
TI  - The development of reading in children who speak English as a second language.
AB  - Patterns of reading development were examined in native English-speaking (L1)
      children and children who spoke English as a second language (ESL). Participants
      were 978 (790 L1 speakers and 188 ESL speakers) Grade 2 children involved in a
      longitudinal study that began in kindergarten. In kindergarten and Grade 2,
      participants completed standardized and experimental measures including reading,
      spelling, phonological processing, and memory. All children received phonological
      awareness instruction in kindergarten and phonics instruction in Grade 1. By the
      end of Grade 2, the ESL speakers' reading skills were comparable to those of L1
      speakers, and ESL speakers even outperformed L1 speakers on several measures. The
      findings demonstrate that a model of early identification and intervention for
      children at risk is beneficial for ESL speakers and also suggest that the effects
      of bilingualism on the acquisition of early reading skills are not negative and
      may be positive.

PMID- 14584982
TI  - Modeling growth in boys' aggressive behavior across elementary school: links to
      later criminal involvement, conduct disorder, and antisocial personality
      disorder.
AB  - The present study used general growth mixture modeling to identify pathways of
      antisocial behavior development within an epidemiological sample of urban,
      primarily African American boys. Teacher-rated aggression, measured
      longitudinally from 1st to 7th grade, was used to define growth trajectories.
      Three high-risk trajectories (chronic high, moderate, and increasing aggression)
      and one low-risk trajectory (stable low aggression) were found. Boys with chronic
      high and increasing trajectories were at increased risk for conduct disorder,
      juvenile and adult arrest, and antisocial personality disorder. Concentration
      problems were highest among boys with a chronic high trajectory and also
      differentiated boys with increasing aggression from boys with stable low
      aggression. Peer rejection was highest among boys with chronic high aggression.
      Interventions with boys with distinct patterns of aggression are discussed.

PMID- 14584983
TI  - Sexual risk taking in adolescence: the role of self-regulation and attraction to
      risk.
AB  - Precursors of adolescent sexual risk taking were examined in a multiethnic sample
      consisting of 443 children (51% girls) of National Longitudinal Survey of Youth
      participants. Respondents were 12-13 years old in 1994 and 16-17 in 1998.
      Controlling for demographic and contextual factors, self-regulation--but not risk
      proneness--was significantly (modestly) associated with overall sexual risk
      taking 4 years later. Analyses of individual sexual behaviors indicated that self
      regulation may affect choices made after becoming sexually active (e.g., number
      of partners) rather than the initiation of sexual activity. Measures of parent
      and peer influence had independent effects on sexual risk taking but did not
      moderate the effects of self-regulation and risk proneness. Findings add to the
      growing literature on implications of self-regulation for individual development.

PMID- 14584984
TI  - Privileged treatment of toddlers: cultural aspects of individual choice and
      responsibility.
AB  - This study examined the idea that toddlers in some communities are accorded a
      privileged status in which they are allowed what they want, assumed not yet to
      "understand" how to cooperate. U.S. middle-class and Guatemalan Mayan mothers and
      3- to 5-year-old siblings were observed while the siblings and toddlers (14-20
      months) both sought access to attractive objects. The Mayan toddlers' desires
      were usually respected by both the mothers and the siblings, who often
      voluntarily cooperated without mothers' intervention. In contrast, the U.S.
      middle-class toddlers seemed to be expected to follow the same rules for sharing
      (with some leniency) as the older children. The Mayan pattern fits a cultural
      model prioritizing both responsibility and respect for others' freedom of choice.

PMID- 14584985
TI  - Stability and transitions in mother-infant face-to-face communication during the
      first 6 months: a microhistorical approach.
AB  - In this study the authors attempted to unravel the relational, dynamical, and
      historical nature of mother-infant communication during the first 6 months.
      Thirteen mothers and their infants were videotaped weekly from 4 to 24 weeks
      during face-to-face interactions. Three distinct patterns of mother-infant
      communication were identified: symmetrical, asymmetrical, and unilateral. Guided
      by a dynamic systems perspective, the authors explored the stability of and
      transitions between these communication patterns. Findings from event history
      analysis showed that (a) there are regularly recurring dyadic communication
      patterns in early infancy, (b) these recurring patterns show differential
      stabilities and likelihoods of transitions, (c) dynamic stability in dyadic
      communication is shaped not only by individual characteristics (e.g., infant sex
      and maternal parity) but also by the dyad's communication history, and (d)
      depending on their recency, communication histories varying in temporal proximity
      exert differential effects on the self-organization processes of a dyadic system.

PMID- 14584986
TI  - Pathways to violence in the children of mothers who were depressed postpartum.
AB  - The impact of postnatal depression on a child's risk for violent behavior was
      evaluated in an urban British community sample (N=122 families). Mothers were
      interviewed during pregnancy, at 3 months postpartum, and when the child was 1,
      4, and 11 years of age. Mothers, teachers, and children reported on violent
      symptoms at age 11. Structural equation modeling revealed that the child's
      violence was predicted by the mother's postnatal depression even when her
      depression during pregnancy, her later history of depression, and family
      characteristics were taken into account. Violence was associated with symptoms of
      attention-deficit/hyperactivity disorder and problems with anger management.
      Children were most violent if mothers had been depressed at 3 months and at least
      once thereafter.

PMID- 14584987
TI  - A perspective on judgment and choice: mapping bounded rationality.
AB  - Early studies of intuitive judgment and decision making conducted with the late
      Amos Tversky are reviewed in the context of two related concepts: an analysis of
      accessibility, the ease with which thoughts come to mind; a distinction between
      effortless intuition and deliberate reasoning. Intuitive thoughts, like percepts,
      are highly accessible. Determinants and consequences of accessibility help
      explain the central results of prospect theory, framing effects, the heuristic
      process of attribute substitution, and the characteristic biases that result from
      the substitution of nonextensional for extensional attributes. Variations in the
      accessibility of rules explain the occasional corrections of intuitive judgments.
      The study of biases is compatible with a view of intuitive thinking and decision
      making as generally skilled and successful.

PMID- 14584988
TI  - An elusive honor: psychology, behavior, and the Nobel Prize.
AB  - Apart from economics, the human sciences have not generally been rewarded with
      high honors from the world community. Psychology has been awarded the distinction
      of a Nobel Prize only when it has served a role in explicating human behavior in
      relation to economics. Yet psychological science has played no small part in the
      work of a number of Nobel Prize winners. This section addresses a selection of
      that work. Some of the winners of the Nobel Prize in the field of psychology are
      briefly reviewed. In addition, this selection introduces the papers in this
      issue.

PMID- 14584989
TI  - Experiences of collaborative research.
AB  - The author's personal history of the research that led to his recognition in
      economics is described, focusing on the process of collaboration and on the
      experience of controversy. The author's collaboration with Amos Tversky dealt
      with 3 major topics: judgment under uncertainty, decision making, and framing
      effects. A subsequent collaboration, with the economist Richard Thaler, played a
      role in the development of behavioral economics. Procedures to make controversies
      more productive and constructive are suggested.

PMID- 14584990
TI  - Behavioral science and the Nobel Prize: a history.
AB  - The Nobel Prizes began a little over a century ago, established by the last will
      and testament of Alfred Nobel to recognize those individuals "who. shall have
      conferred the greatest benefits on mankind" (R. M. Friedman, 2001, p. 13). No
      social science prizes were established among the original five categories,
      consequently behavioral research has received little recognition. Using archival
      records from several locations, particularly the Nobel committee records from the
      Karolinska Institute in Stockholm, which selects the Nobel Prize in Physiology or
      Medicine, this article provides a history of the scientists whose work was
      related to psychology and who won or lost the attempt for Nobel fame. It
      concludes with a discussion of the importance of behavioral science in the 21st
      century in the context of the subject domains of the Nobel Prizes.

PMID- 14584991
TI  - Georg von Bekesy: visualization of hearing.
AB  - Georg von Bekesy received the Nobel Prize in 1961 for his research on the
      functioning of the auditory system. In psychoacoustics, Bekesy both extended and
      perfected the lines of research begun by von Helmholtz in the 19th century. First
      in his native Hungary and later at Harvard, Bekesy used novel and imaginative
      devices and methods to observe and model the functioning of the inner ear. He
      also explored the nature of sensory inhibition by which the nervous system
      sharpens sensory transitions.

PMID- 14584992
TI  - The 1973 Nobel Prize for Physiology or Medicine: recognition for behavioral
      science?
AB  - The Nobel Prize for Physiology or Medicine for 1973 was awarded to 3 ethologists:
      Karl von Frisch, Konrad Lorenz, and Nikolaas Tinbergen. This was a landmark event
      in the history of the field of ethology and potentially for the behavioral
      sciences more broadly. For the first time, the prize was awarded for research of
      a purely behavioral nature. The language used in making the award emphasized the
      implications of ethological work for human health and appeared to suggest that
      more such awards might be forthcoming; few were. The author provides an overview
      of the 3 men, their work, the events surrounding the award, the controversy that
      arose, and the significance of the award as viewed in contemporary perspective.

PMID- 14584993
TI  - Herbert A. Simon: Nobel Prize in Economic Sciences, 1978.
AB  - In 1978, Herbert A. Simon won the Nobel Prize in Economic Sciences, the same
      Nobel won by Daniel Kahneman in 2002. Simon's work in fact paved the way for
      Kahneman's Nobel. Although trained in political science and economics rather than
      psychology, Simon applied psychological ideas to economic theorizing. Classical
      and neoclassical economic theories assume that people are perfectly rational and
      strive to optimize economic outcomes. Simon argued that human rationality is
      constrained, not perfect, and that people seek satisfactory rather than ideal
      outcomes. Despite his Nobel, Simon felt isolated in economics and ultimately
      moved into psychology. Nevertheless, his ideas percolated through the economic
      community, so that Kahneman, whose research advanced Simon's broad perspective,
      could be the psychologist who won the Nobel in economics.

PMID- 14584994
TI  - The Flynn effect and U.S. policies: the impact of rising IQ scores on American
      society via mental retardation diagnoses.
AB  - Over the last century, IQ scores have been steadily rising, a phenomenon dubbed
      the Flynn effect. Because of the Flynn effect, IQ tests are periodically
      renormed, making them harder. Given that eligibility for mental retardation (MR)
      services relies heavily on IQ scores, renormed tests could have a significant
      impact on MR placements. In longitudinal IQ records from 9 sites around the
      country, students in the borderline and mild MR range lost an average of 5.6
      points when retested on a renormed test and were more likely to be classified MR
      compared with peers retested on the same test. The magnitude of the effect is
      large and affects national policies on education, social security, the death
      penalty, and the military. This paper reports the perceptions of professionals as
      they relate to IQ score fluctuations in normal, borderline, and/or MR
      populations.

PMID- 14584995
TI  - Challenges to professional psychology education in the 21st century: response to
      Peterson.
AB  - Professional psychology education faces many critical challenges brought about by
      the major changes occurring in the health care arena. This article shows that
      professional schools and programs have a good record of responding to these
      challenges and of taking proactive steps sponding to prepare their graduates for
      new health care roles and delivery systems. Data on admissions to psychology
      doctoral training programs demonstrate little support for the toral concerns
      raised by Donald R. Peterson (2003, this issue) about the preparation of students
      for graduate training in professional programs. Although quality concerns are
      important to investigate, such examination best resides with portant the American
      Psychological Association's Committee on Accreditation, which has the promotion
      of quality and excellence in professional psychology education and training as
      its major goal and responsibility.

PMID- 14584996
TI  - Moral implications of globalization and identity.

PMID- 14584997
TI  - Globalization and liberation: two sides, same coin?

PMID- 14584999
TI  - Enhancing communication through visual Aids in clinical practice.

PMID- 14585000
TI  - Methodolatry and graphicacy.

PMID- 14585002
TI  - Dieting: false hope or falsely accused?

PMID- 14585003
TI  - The case against false hope.

PMID- 14585004
TI  - Renewed hope for self-change.

PMID- 14585006
TI  - Rethinking fragmentation and diversity in psychology.

PMID- 14585007
TI  - Unintended consequences: ventures and misadventures in the education of
      professional psychologists.
AB  - Increasing professionalization of psychology, accelerated by expansion of
      professional schools, has evoked concern among critics, who claim that many
      practitioners ignore scientific research and engage in practices that are
      demonstrably useless or harmful. Recent data on admissions to professional
      schools and performance of professional school graduates show cause for concerns
      of the critics. If psychology is to maintain its stature as a profession,
      exclusionary controls as well as hortatory requirements for the practice of
      psychology and the education of practitioners must be established and enforced.
      Before more stringent standards can be imposed, convincing means for evaluating
      competence in professional work and quality in professional education must be
      developed. Local and institutional actions to advance those aims are proposed.

PMID- 14585008
TI  - Symbolic control of visual attention: The role of working memory and attentional
      control settings.
AB  - This study examined how 1 symbol is selected to control the allocation of
      attention when several symbols appear in the visual field. In Experiments 1-3,
      the critical target feature was color, and it was found that uninformative
      central arrows that matched the color of the target were selected and produced
      unintentional shifts of attention (i.e., involuntary, initiated slowly, producing
      long-lasting facilitatory effects). Experiment 4 tested whether such selection is
      the result of an attentional filter or of a competition bias due to a match of
      incoming information against integrated object representations stored in working
      memory. Here, the critical feature was shape and color was irrelevant, but
      matching color arrows were still selected. Thus, features of objects in working
      memory will bias the selection of symbols in the visual field, and such selected
      symbols are capable of producing unintentional shifts of attention. ((c) 2003
      APA, all rights reserved)

PMID- 14585009
TI  - Explicit mechanisms do not account for implicit localization and identification
      of change: An empirical reply to Mitroff et al. (2002).
AB  - Several recent findings support the notion that changes in the environment can be
      implicitly represented by the visual system. S. R. Mitroff, D. J. Simons, and S.
      L. Franconeri (see record 2002-15293-003) challenged this view and proposed
      alternative interpretations based on explicit strategies. Across 4 experiments,
      the current study finds no empirical support for such alternative proposals.
      Experiment 1 shows that subjects do not rely on unchanged items when locating an
      unaware change. Experiments 2 and 3 show that unaware changes affect performance
      even when they occur at an unpredictable location. Experiment 4 shows that the
      unaware congruency effect does not depend simply on the pattern of the final
      display. The authors point to converging evidence from other methodologies and
      highlight several weaknesses in Mitroff et al's theoretical arguments. It is
      concluded here that implicit representation of change provides the most
      parsimonious explanation for both past and present findings. ((c) 2003 APA, all
      rights reserved)

PMID- 14585010
TI  - On doing two things at once: III. Confirmation of perfect timesharing when
      simultaneous tasks are ideomotor compatible.
AB  - A. G. Greenwald and H. G. Shulman (see record 1974-10326-001) found that 2 tasks
      characterized by ideomotor (IM) compatibility could be perfectly timeshared
      (i.e., performed simultaneously without mutual interference). The 2 tasks were
      pronouncing "A" or "B" in response to hearing those letter names, and making a
      manual left or right response to seeing a left- or right-positioned arrow. M.-C.
      Lien, R. W. Proctor, and P. A. Allen (2002) did not replicate Greenwald and
      Shulman's result, and concluded that their finding of perfect timesharing of 2 IM
      compatible tasks might not be replicable. In the present research, Experiment 1
      replicated Greenwald and Shulman's 1973 finding while also supporting the
      conclusion that Lien et al's nonreplication was due to their not instructing
      subjects to make 2 responses simultaneously in their timeshared task. Experiment
      2 again replicated the perfect timesharing finding, using an alternative control
      procedure that mixed manual and vocal tasks in the same block. ((c) 2003 APA, all
      rights reserved)

PMID- 14585011
TI  - Accuracy and precision of binocular 3-D motion perception.
AB  - In principle, information for 3-D motion perception is provided by the
      differences in position and motion between left- and right-eye images of the
      world. It is known that observers can precisely judge between different 3-D
      motion trajectories, but the accuracy of binocular 3-D motion perception has not
      been studied. The authors measured the accuracy of 3-D motion perception. In 4
      different tasks, observers were inaccurate, overestimating trajectory angle,
      despite consistently choosing similar angles (high precision). Errors did not
      vary consistently with target distance, as would be expected had inaccuracy been
      due to misestimates of viewing distance. Observers appeared to rely strongly on
      the lateral position of the target, almost to the exclusion of the use of depth
      information. For the present tasks, these data suggest that neither an accurate
      estimate of 3-D motion direction nor one of passing distance can be obtained
      using only binocular cues to motion in depth. ((c) 2003 APA, all rights reserved)

PMID- 14585012
TI  - Parallel allocation of attention prior to the execution of saccade sequences.
AB  - In a series of 5 experiments, the allocation of attention prior to the execution
      of saccade sequences was examined by using a dual-task paradigm. In the primary
      task, participants were required to execute a sequence of 2 endogenous saccades.
      The secondary task was a forced-choice letter identification task. During the
      programming of the saccade sequences, letters were briefly presented at the
      saccade goals and at no-saccade locations. The results showed that performance
      was better for letters presented at any of the saccade goals than for letters
      presented at any of the no-saccade locations. The results support a spatial model
      that assumes that prior to the execution of a saccade sequence, attention is
      allocated in parallel to all saccade goals. ((c) 2003 APA, all rights reserved)

PMID- 14585013
TI  - Modulation of object-based attention by spatial focus under endogenous and
      exogenous orienting.
AB  - In R. Egly, J. Driver, and R. D. Rafal's (1994) influential double-rectangle
      spatial-cuing paradigm, exogenous cues consistently induce object-based
      attention, whereas endogenous cues generally induce space-based attention. This
      difference suggests an interdependency between mode of orienting (endogenous vs
      exogenous) and mode of selection (object based vs space based). However, mode of
      orienting is generally confounded with initial focus of attention: Endogenous
      orienting begins with attention focused on a central cue, whereas exogenous
      orienting begins with attention widely spread. In this study, an attentional
      focusing hypothesis is examined and supported by experiments showing that for
      both endogenous and exogenous cuing, object-based effects are obtained under
      conditions that encourage spread attention, but they are attenuated under
      conditions that encourage focused attention. General implications for object
      based attention are discussed. ((c) 2003 APA, all rights reserved)

PMID- 14585015
TI  - Top-down contingencies in peripheral cuing: The roles of color and location.
AB  - According to contingent-processing accounts, peripheral cuing effects are due to
      the cues' inadvertent selection for processing by control settings set up for
      targets (e.g., C. L. Folk, R. W. Remington, & J. C. Johnston, 1992).
      Consequently, cues similar to targets should have stronger effects than do
      dissimilar cues. In the current study, this prediction is confirmed for cue
      target combinations similar or dissimilar in the static features of color
      (Experiments 1-3) and location (Experiment 4), even when both cues and targets
      share the dynamic feature of abrupt onset. Perceptual priming (Experiment 2) and
      reallocation of attention did not account for similar-dissimilar differences
      (Experiments 3 and 4). The results are best explained by top-down-contingent
      attentional effects of the similar cues. Implications for bottom-up accounts of
      peripheral cuing effects are discussed. ((c) 2003 APA, all rights reserved)

PMID- 14585014
TI  - The effects of recent practice on task switching.
AB  - Four experiments investigated the effect of recent selective practice on the cost
      of switching between 2 tasks afforded by letter-digit pairs: alphabet arithmetic
      and shape comparison. Experiments 1 and 2 found a greater cost associated with
      switching to the more recently practiced task: evidence that task-set inertia
      contributes to switching costs. Experiment 3 found this effect to be limited to
      trials on which a recently trained stimulus followed another such stimulus: a
      result problematic for all current theories of task-set priming. Experiment 4
      showed that the effect of recent practice was eliminated by active preparation
      for a task switch: It appears that endogenous task-set preparation reduces the
      effects of task-set inertia. ((c) 2003 APA, all rights reserved)

PMID- 14585016
TI  - Auditory feedback in music performance: Evidence for a dissociation of sequencing
      and timing.
AB  - Four experiments examined temporal relationships between actions and auditory
      feedback in music performance. Experiment 1 incorporated phase shifts of
      feedback, which disrupted produced timing but not overall accuracy. Experiment 2
      incorporated period shifts of pitch contents for synchronized feedback that
      primarily disrupted accuracy more than timing. Experiment 3 incorporated combined
      phase and period shifts, which caused moderate disruption to timing and accuracy
      and revealed interactive effects of period and phase shifts on production. A 4th
      experiment included all feedback conditions in the same session to confirm
      differences across Experiments 1-3. These results are consistent with the view
      that actions and their perceptual consequences are coordinated in a way that
      distinguishes timing (phase shifts) from sequencing (period shifts). ((c) 2003
      APA, all rights reserved)

PMID- 14585017
TI  - The psychological refractory period of stopping.
AB  - The author examined whether the act of control of stopping is subject to the
      psychological refractory period (PRP) and whether stopping causes a PRP for the
      processing of subsequent stimuli. The task was to execute or to stop a rapid
      finger tapping. PRP interference was predicted for double-stimulation trials, in
      which 2 signals to tap or stop were presented in rapid succession. The
      experiments showed that stopping ongoing action is subject to and produces PRP
      interference similar to starting. Responses to signals to continue an ongoing
      action do not produce PRP interference. The results suggest that selection or
      initiation of new responses, but not mere response choice, constituted the
      processing bottleneck that caused the PRP in the present task. Further results
      indicate that the inhibition of not-yet-executed actions, in contrast to action
      termination, does not suffer PRP interference and that response inhibitions and
      terminations should be distinguished. ((c) 2003 APA, all rights reserved)

PMID- 14585018
TI  - Naive optics: Predicting and perceiving reflections in mirrors.
AB  - Undergraduate students predicted what would be made visible by a planar mirror. A
      paper-and-pencil task confirmed previous findings that when approaching a mirror
      from the side, participants expected to see their reflection in the mirror
      earlier than they actually would. This early response was found for all mirrors
      when the observer moved horizontally--even when the mirror was placed on the
      floor or the ceiling--but not when the observer moved vertically (in a lift). The
      data support the hypothesis that many people imagine the world in the mirror as
      rotated around the vertical axis. When participants had to judge manipulated
      mirror reflections according to their naturalness, a high degree of tolerance was
      found. In contrast to the prediction task, a rotation around the vertical axis
      was judged to be less natural than other distortions. The authors conclude that
      perceptual knowledge and predictive knowledge lead to different patterns of
      errors. ((c) 2003 APA, all rights reserved)

PMID- 14585019
TI  - Attentional capture in singleton-detection and feature-search modes.
AB  - Six experiments were conducted to determine the circumstances under which an
      irrelevant singleton captures attention. Subjects searched for a target while
      ignoring a salient distractor that appeared at different stimulus onset
      asynchronies (SOAs) prior to each search display. Spatial congruency and
      interference effects were measured. The strategies available to find the target
      were controlled (only singleton-detection mode, only feature-search mode, or both
      search strategies available). An irrelevant abrupt onset captured attention in
      search for a color target, across SOAs, whatever strategies were available. In
      contrast, in search for a shape target, an irrelevant color singleton captured
      attention in the singleton-detection condition but delayed response at its
      location in the feature-search condition, across SOAs. When both strategies were
      available, capture was short lived (50- to 100-msec SOAs). The theoretical
      implications of these findings in relation to current views on attentional
      capture are discussed. ((c) 2003 APA, all rights reserved)

PMID- 14585020
TI  - Visual search for singleton feature targets across dimensions: Stimulus- and
      expectancy-driven effects in dimensional weighting.
AB  - Four pop-out search experiments investigated whether dimension-based visual
      attention is top-down modulable. Observers searched for singleton feature targets
      defined, variably across trials, by a color or an orientation difference to
      nontargets. Observers were precued to the most probable target-defining dimension
      (e.g., by the word color) or feature (red) on a given trial. Results revealed
      expedited reaction times (RTs) for valid-dimension targets relative to neutral
      cue conditions, and slowed RTs for invalid-dimension targets. Cue information as
      to precise target feature yielded some extra effect only for color targets. The
      dimensional cuing significantly reduced, but did not abolish, the dimension
      specific influence of the previous target on detection of the current target
      (same-dimension RT < different-dimension RT). These findings confirm that top
      down dimensional set modulates stimulus-driven dimension processes in the
      detection of pop-out signals. ((c) 2003 APA, all rights reserved)

PMID- 14585021
TI  - Absence of perceptual processing during reconfiguration of task set.
AB  - The authors manipulated stimulus contrast and response-stimulus interval in the
      alternating runs paradigm to investigate whether early processing could be
      carried out during a task switch. Subjects alternated between judging the
      magnitude and the parity of a digit. The results suggested that early processing
      was not carried out during the task switch (Experiment 1), even in the absence of
      potentially confounding auditory or visual warning signals (Experiment 2). This
      processing was, however, carried out in parallel with a demanding operation in a
      2nd task (Experiment 3), using the display parameters of Experiments 1 and 2 in
      the psychological refractory period paradigm. It is concluded that, functionally,
      task switching may impose a hard bottleneck even for very early stimulus
      processing. ((c) 2003 APA, all rights reserved)

PMID- 14585022
TI  - Characteristics of covert and overt visual orienting: Evidence from attentional
      and oculomotor capture.
AB  - Five visual search experiments found oculomotor and attentional capture
      consistent with predictions of contingent orienting, contrary to claims that
      oculomotor capture is purely stimulus driven. Separate saccade and attend-only
      conditions contained a color target appearing either singly, with an onset or
      color distractor, or both. In singleton mode, onsets produced oculomotor and
      attentional capture. In feature mode, capture was absent or greatly reduced,
      providing evidence for top-down modulation of both types of capture. Although
      attentional capture by color abstractors was present throughout, oculomotor
      capture by color occurred only when accompanied by transient change, providing
      evidence for a dissociation between oculomotor and attentional capture.
      Oculomotor and attentional capture appear to be mediated by top-down attentional
      control settings, but transient change may be necessary for oculomotor capture.
      ((c) 2003 APA, all rights reserved)

PMID- 14585034
TI  - [Drug addiction: consumption and consequences in continous change].

PMID- 14585023
TI  - Inhibition of return: Dissociating attentional and oculomotor components.
AB  - Inhibition of return (IOR) describes a performance decrement for stimuli
      appearing at recently cued locations. Both attentional and motor processes have
      been implicated in the IOR effect. The present data reveal a double dissociation
      between the attentional and motor components of IOR whereby the motor-based
      component of IOR is present when the response is oculomotor, and the attention
      based component of IOR is present when the response is manual. These 2 distinct
      components should be considered and studied separately, as well as in relation to
      each other, if a comprehensive theory of IOR is to be achieved. ((c) 2003 APA,
      all rights reserved)

PMID- 14585035
TI  - [Profile of drug users admitted to a hospital].
AB  - AIM: To know the clinical and epidemiological characteristics of drug users
      admitted to a hospital. METHOD: A descriptive-retrospective study. RESULTS: Of
      the 123 patients admitted to the hospital (a total of 155 admissions), 84,5% of
      them were admitted through the Emergency Department. Their main age was 33 +/- 6
      and the 65,9% were male. The 90,2% were injecting drug users (IDU). The main age
      of initiation in the use of drugs was 21 years; and the time of addiction ranged
      from I to 30 years (69 patients remained addicted to drugs for 10 years or more).
      There were 102 HCV infections and 13 HBV infections, and 50 patients tested
      positive for at least I serological marker of hepatitis B infection; 65 were HIV
      positive (all ofthem were IDU) and 61 were coinfected with HCV. 34 patients had
      AIDS. Infectious diseases were responsible for 105 of the 155 admissions to
      hospital. In 134 occasions the patients were discharged and 11 died. CONCLUSIONS:
      Most of the patients were male. The admissions to hospital were mostly due to
      infectious diseases. The most commonly associated pathologies seen were to be HIV
      positive and to carry HCV. The outcome of patients was mainly the discharge from
      hospital, and those who died were all HIV positive.

PMID- 14585036
TI  - [The medical care in internal medicine in relation to consultations].
AB  - OBJECTIVE: To study the characteristics of interconsultations from Traumatology
      (TM), Urology (UR) and Psychiatry (PC) to Internal Medicine (IM). MATERIAL AND
      METHODS: Interconsultations from TM, UR and PC to IM from November 2000-April
      2001 were analyzed. A medical care program was established and supervised by a
      physician specifically assigned for this purpose. RESULTS: 105 TM, 30 PC and 23
      UR interconsultations were reported. The mean age and percentage of women were
      greater for the TM group. Hip fracture was the principal cause for hospital
      admission. Cardiac pathologies were the most frequently associated pathology. The
      mean Charlson Index was 6.07 (TM), 3.10 (PC) and 6.17 (UR). The principal cause
      for consultation was dyspnea. The most frequent diagnosis was respiratory
      infection. The mortality rates for the patients were 9.52% (TM), 13% (UR) and 0%
      (PC). When comparing rapid medical care for patients admitted to TM from 2000
      2001 versus 1999-2000, we found the response to interconsultations to be most
      rapid. and 9.95% mortality for the 2000-2001 period versus 13.84% mortality for
      the 1999-2000 period. CONCLUSIONS: The TM interconsultations proved to be both
      complex and frequent. The majority of interconsultations were for elderly women
      with hip fractures and multiple pathologies requiring rapid medical assistance. A
      response system adapted to these interconsultations improved the quality of care
      and mortality.

PMID- 14585037
TI  - [Treatment of malignant colorectal obstruction by means of endoscopic insertion
      of self-expandable metallic stents].
AB  - BACKGROUND AND AIM: Self-expandable metallic stents are being used increasingly
      to treat the obstruction of different segments of the digestive tract and biliary
      tree. We present our centre experience on the initial resolution of malignant
      colorectal obstruction by means of this type of stents. PATIENTS AND METHODS:
      During a 18-month period, 13 patients patients suffering from malignant
      obstruction at the level of rectum, sigmoid or descending colon tried to be
      initially treated by means of endoscopic insertion of stents (non covered enteral
      Wallstents). Ten procedures were performed with both endoscopy and fluroscopy and
      three with only endoscopy. RESULTS: In 12 of the 13 patients (92,3%) the
      obstruction was solved by means of correct stent insertion. All the exclusively
      endoscopic procedures (without fluoroscopy) were successful. Six (50 %) patients
      with tumours at the rectosigmoid underwent later scheduled surgery. In the
      remaining six ones (a patient with an ovarian carcinoma and five with colonic
      adenocarcinoma) the stents were considered to be a palliative definitive
      treatment. Stent migration was observed in two of these patients and both were
      extracted endoscopically. Only one patient needed to have another stent inserted.
      A tumoural colo-vesical fistula developed in another patient in the palliative
      group, inside the previous inserted stent, and was treated by coaxial insertion
      of an esophageal Ultraflex. There were no other complications or mortality
      related to the endoscopic procedures. CONCLUSIONS: Self-expandable metallic
      stents might be considered, in general, as the initial treatment for the
      malignant obstruction at the level of rectum, sigmoid and descending colon

PMID- 14585038
TI  - [Prognostic significance and clinic utility of serum and immunohistochemical
      cathepsin B levels in colorectal cancer].
AB  - BACKGROUND: Aproximately one third of node-negative colorectal cancer recur
      suggesting the presence of micrometastasis not detected by conventional
      histopathologic methods. We think that the role of enzymes like Cathepsin B play
      in the process of invasion and metastasis in colorectal cancer might identify at
      earlier stages patients with high risk of shorter survival and who need more
      aggressive treatment. Our porpuse is to evaluate the prognostic significance of
      preoperative serum and inmunohistochemical levels of cathepsin B to identify
      colorectal carcinomas with worse prognostic. METHODS: Fifty five patients
      undergoing surgical treatment for colorectal cancer from 1998 to 2000. As a
      control group sera from 23 patients with acute appendicitis. Serum levels of
      cathepsin B were obtained preoperatively (KRKA, Novo Slovenia;ng/ml); cathepsin B
      inmunoreactivity was determinated after surgical treatment, (C-19, Santa Cruz
      Biotechnology). Serum levels of CEA (Inmulit 2000 CEA), and CA 19,9 (Inmulite Gi
      Ma, Diagnostic Products Corporation, Los Angeles, CA), and p53 expression (Dako)
      were determinated in patients with colorectal cancer. Survival analysis was
      realized using Cox and Kaplan-Meier methods (SPSS 10.0 for Windows). RESULTS: The
      mean age of patients with colorectal cancer was 68 years (range 39-87 years). 29
      males and 26 females. Tumor size was 4.6 cms., range 1-12. Rectal localization,
      32.2%. Moderately differentiated, 49.1%. The median serum and inmunohistochemical
      levels of cathepsin B were 5.74 ng/ml and 29.56% in patients with acute
      appendicitis respectively. Preoperative serum levels in patients with colorectal
      cancer were: CEA, 46.04 ng/ml (range 0.21-7.32 ); CA 19,9, 110.52 UI/ml, (range
      2.5-1920); and Cathepsin B, 6.94 ng/ml, range 3.57-11.6). Inmunohistochemical
      results were: p53, 44.36%, (range 0-95); Cathepsin B, 66.9% (range 10-90). Serum
      and inmunhistochemical values were significantly increased in patients with
      colorectal cancer when compared with control group, p=0,011 and p=0,000. High
      serum levels of cathepsib B were significantly associated wiyh shorter survival
      of patients with colorectal cancer in univariate and multivariate methods,
      p=0.041;HR 1.281 95%CI (1.043-1.716) and p= 0.022; HR 1.338.955 CI (1.043-1.716).
      CONCLUSIONS: Cathepsin B can be used like an independent prognostic tumoral
      marker in colorectal cancer. Preoperative serum levels over 6.94 ng/ml, are
      associated with worse prognostic and shorter survival.

PMID- 14585039
TI  - [A rare presentation of tuberculosis. Miliary tuberculosis in a immunocompetent
      patient].
AB  - Currently, miliary TB has a higher incidence among the elderly and
      immunodepressed patients, and exceptionally in young adults. A case of miliary
      tuberculosis was diagnosed in a young immunocompetent patient without using
      invasive techniques. The clinical and diagnostic implications will be discussed.

PMID- 14585040
TI  - [Asymptomatic aortic valve stenosis and sudden death].
AB  - Dyspnea, angor and syncope are the most characteristic symptoms in stenosis
      aortic valve disease. Sudden death, as part of natural history of symptomatic
      stenosis aortic valve, is well know. On the other hand, sudden death in
      asymptomatic stenosis aortic valve is rarer. Different guidelines recommend a
      conservative management of these patients. We present here the case of a 58 year
      old woman, previously healthy, who arrived at Hospital because of sudden dyspnea
      at rest. The patient was diagnosed of pulmonary edema and died two hours later.
      Necropsy showed a stenosis aortica valve with a valve area of less than 0.8 cm2.
      We make a short review in medical literature about the incidence of sudden death
      in asymptomatic stenosis aortic valve, the risk groups and their management.

PMID- 14585041
TI  - [Antiphospholipid syndrome. The use of transesophageal echocardiography].
AB  - Antiphospholipid syndrome (APS) is defined by the presence of arterial and venous
      thromboses, recurrent fetal death, cerebrovascular accidents, hemolytic anaemia,
      thrombocytopenia and various other manifestations in different organs. APS is a
      clinical entity that can appear commonly alongside systemic lupus erithemathous
      on it can occur as a primary disease. The syndrome is defined by the presence of
      antiphospholipid antibodies in serum, a group of immunoglobulins (IgG, IgM, IgA
      or an mixture of them) that adopt an hexagonal configuration when they are
      incubated at 37grades C. In APS, it is rather common to find cardiac lesions such
      as non-verrucous endocarditis, valvular lesions (especially of the mitral valve),
      microvascular cardiac disease and more risk of thrombosis at this level, myxomas
      that could be the cause of a systemic inflammation in relation to the production
      of antiphospholipid antibodies, intracardiac thrombii and congenital heart
      disease. We present the case of a woman with APS associated with interauricular
      communication whose initial diagnosis were pulmonary thromboembolism and
      cerebrovascular stroke. We were able to diagnose the cardiac abnormality by the
      use of transesophagic echocardiography. We propose the use of this imaging
      technique for patients with APS even though the transthoracic Doppler
      echocardiography was found to be normal. In this way we will be able to rule out
      cardiac lesions which could also be the cause of embolic manifestations.

PMID- 14585042
TI  - [Localized Castleman's disease: description of a case and review of the
      literature].
AB  - Castleman's disease is a rare entity which is caracterized by its histological
      features: hyperplasia of lymph nodes and capillary proliferation. Two
      histological patterns has been described: hyaline vascular type and plasma cell
      type. From a clinical viewpoint has been identified two different clinical
      course: a localized type (ECL) usually of benign clinical course and a
      multicentric type (ECM) of worst prognosis. We present a case of Castleman"s
      disease localized in the neck region in which the excision was both diagnostic
      and therapeutic. The variety histological was hyaline-vascular type.

PMID- 14585043
TI  - [Massive venous thrombosis with cardiac invasion as primary manifestation of
      hepatocarcinoma].
AB  - Hepatocellular carcinoma has a tendency to invade vascular structures. However,
      extension into the hepatic veins or heart is uncommon. We describe the case of a
      68 years old man with chronic viral hepatitis type C, consulting about edema and
      pain in his left leg. Doppler scan showed deep venous thrombosis in that level
      and computed tomography of thorax and abdomen showed complete thrombosis of the
      inferior cava vein, thrombosis of the left suprahepatic vein, a voluminous
      thrombus in the right atrium and an irregular mass in the liver. Alpha
      fetoprotein was 77,046 ng/ml The biopsy of the rigth atrium thrombus demonstrated
      diseminated hepatocellular carcinoma. We comment the patient progress after
      surgery, the incidence, clinical symptoms, and therapy options for these
      patients.

PMID- 14585044
TI  - [Guidelines for clinical management of bioterrorism bacterial diseases: anthrax,
      plague, turalemia and brucellosis].

PMID- 14585045
TI  - [Spontaneous dissection of the internal carotid artery].

PMID- 14585047
TI  - [Embolic splenic infarction].

PMID- 14585046
TI  - [Patient with septic polyarthritis and multifocal osteomyelitis due to
      hematogenous dissemination of Staphylococcus aureus].

PMID- 14585048
TI  - [Intermittent fever as the initial manifestation of giant cavernous hemangioma of
      the liver].

PMID- 14585049
TI  - [Spontaneous resolution of a primary thymic cyst].

PMID- 14585050
TI  - [Primary systemic amyloidosis and dilated cardiomyopathy].

PMID- 14585051
TI  - Cardiovascular consequences of the obesity pandemic: need for action.
AB  - Due to changes in nutritional patterns and physical activity as well as economic
      growth in developing countries, the prevalence of obesity has reached pandemic
      proportions in the past decades. Consequences of diseases related to obesity,
      such as coronary heart disease, hypertension, diabetes and renal disease, account
      for much of the morbidity in these patients and are rarely treated adequately.
      There is an enormous need to provide information to the general population and
      particularly parents concerning the risks of childhood obesity and the importance
      of regular exercise. Physicians and scientists have now realised that obesity is
      a pathophysiological entity with important clinical complications. Current
      actions to prevent obesity should not only be directed towards the development of
      drugs controlling weight gain, but should also include educational programs,
      which will guarantee adequate awareness and prevention of this disease.

PMID- 14585052
TI  - Pfizer-Pharmacia: the postmerger.

PMID- 14585053
TI  - Platelets, atherosclerosis and the endothelium: new therapeutic targets?
AB  - One of the major causes of morbidity and mortality in the developed world is
      atherosclerosis. Recent research has suggested that the interaction of platelets
      with the endothelium is important in both the progression of atherosclerosis and
      the development of the acute complications of the disease. Both of these cells
      secrete various signalling molecules and express adhesion molecules, which can
      influence the development of pathological states. Certainly, there may be a
      vicious cycle in which platelet activation promotes atherosclerosis; a process
      involving inflammation and the activation of many other cell types (for example,
      leukocytes and smooth muscle cells), which causes further platelet activation.
      Therefore, intense effort has been made to develop therapeutic agents that can
      modulate the function of these cells, with the ultimate aim to retard (or even
      reverse) the progression of atheroma growth.

PMID- 14585054
TI  - New drugs for the treatment of hypercholesterolaemia.
AB  - Endogenous and exogenous pathways determine plasma levels of cholesterol and
      lipoproteins. Plasma cholesterol levels and coronary heart disease risk can be
      reduced pharmacologically by decreasing cholesterol synthesis, increasing its
      elimination and/or reducing its absorption from the intestine. The more profound
      knowledge about cholesterol homeostasis has allowed the development of several
      lipid-lowering drugs with different mechanisms of action, with the purpose of
      reducing both morbidity and mortality associated with coronary heart disease. Two
      new and more potent 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase
      inhibitors (statins), also called superstatins (rosuvastatin and pitavastatin),
      are being studied for their ability to improve lipid profiles. Rosuvastatin is a
      potent, hepato-selective and relatively hydrophilic statin with a low propensity
      for muscle toxicity and drug interactions. Pitavastatin is another statin with a
      high oral bioavailability and minimal propensity for cytochrome p450-mediated
      drug interactions. Rosuvastatin seems to be more potent than other available
      statins while pitavastatin presents with a similar potency to that of
      atorvastatin. Another promising approach for lowering total and low-density
      lipoprotein cholesterol levels is inhibition of cholesterol absorption. A wide
      variety of new agents with the capacity for inhibiting the intestinal cholesterol
      absorption is currently being investigated. Ezetimibe is a selective cholesterol
      absorption inhibitor whose clinical efficacy has been recently demonstrated both
      in monotherapy and in combination with other lipid-lowering drugs. Colesevelam, a
      new bile acid sequestrant, has shown a clinical efficacy similar to that of other
      resins, with minimal gastrointestinal side effects, improving tolerability and
      patient compliance. Other lipid-lowering drugs with the ability to act at the
      enterocyte level, such as avasimibe and implitapide, are currently being
      investigated in humans.

PMID- 14585055
TI  - Novel pharmacological treatments for heart failure.
AB  - Pharmacological therapies remain the primary strategy for treating patients with
      acute and chronic heart failure. Several novel neurohormonal antagonists,
      inotropic agents, immune modulators, and metabolic and replacement therapies are
      currently in development to meet the demands of an increasing number of patients
      with heart failure. The success in drug development in this field will require a
      better understanding of the effects of heart failure on drug dosing, better
      integration of novel and existing drug therapies, the development of more
      reliable surrogate markers to effectively tailor medical therapy to individual
      needs and the ability to detect and treat patients at risk before the onset of
      heart failure.

PMID- 14585056
TI  - Dopamine agonists in Parkinson's disease.
AB  - Levodopa (LD), the immediate precursor of dopamine, is the most effective agent
      in the treatment of Parkinson's disease (PD). While quite successful in treating
      the primary motor deficits of PD, most patients eventually develop LD-related
      motor fluctuation, dyskinesias and other adverse effects associated with chronic
      LD therapy. There is also concern that LD is neurotoxic, although this has not
      been demonstrated in any in vivo studies. Dopamine agonists (DAs) have been shown
      to be about as effective as LD in symptomatic treatment of mild-to-moderate PD.
      In addition, there is a lower tendency to develop motor fluctuations and
      dyskinesias with DA treatment than after initiation of therapy with LD.
      Furthermore, there is preclinical and clinical data to suggest a slowing of
      neurodegeneration with DAs. The adverse effects of DAs are similar to those
      experienced with LD, except that the ergot agents are associated with a small
      risk of tissue fibrosis not noted with the non-ergot DAs.

PMID- 14585057
TI  - Tipranavir: a novel non-peptidic protease inhibitor for the treatment of HIV
      infection.
AB  - Tipranavir (TPV) is a non-peptidic protease inhibitor belonging to the class of 4
      hydroxy-5,6-dihydro-2-pyrones, which exhibits potent and specific activity
      against HIV type I (HIV-1) and 2 (HIV-2). Clinically effective plasma levels of
      TPV are achieved by concomitant administration of ritonavir (RTV). Therefore, TPV
      has been coadministered with RTV in clinical trials. TPV has demonstrated
      antiviral activity against HIV-1 isolates that are resistant to reverse
      transcriptase and selected peptidic protease inhibitors. Therefore, TPV is
      emerging as one of the newer drugs in the armamentarium against HIV-1 in patients
      demonstrating multi-drug resistance. TPV administered orally to humans exhibits
      linear pharmacokinetics at doses of 100 - 2000 mg. Steady-state plasma levels are
      attained within 7 days of initiating multiple dosing. The half-life of the drug
      is approximately 6 h at steady-state. The plasma concentration is lower with
      repeated dosing than predicted from single-dose studies due to induction of the
      cytochrome p450 3A4 isoform of the liver microsomal enzyme system. Phase II
      clinical trials have shown that the administration of TPV and RTV in combination
      is safe and generally well-tolerated in HIV-1-infected adults. Phase III trials
      are underway to compare the efficacy of this drug versus other antiretroviral
      regimens. Gastrointestinal toxicity has been described with TPV, the most
      frequently reported side effects being diarrhoea, nausea, vomiting and abdominal
      pain. There is no known evidence of teratogenicity or effect on fertility. TPV
      dosed twice-daily, in the range of 500 - 1250 mg and combined with 100 - 200 mg
      of RTV has been shown to substantially and durably reduce viral load in HIV-1
      infected drug-naive and experienced patients.

PMID- 14585059
TI  - Preclinical and clinical results with the natural marine product ET-743.
AB  - ET-743 (Yondelis, trabectedin) is a natural marine product with antitumour
      properties derived from the tunicate Ecteinascidia turbinata. ET-743 binds to the
      N2 position of guanine in the minor groove of DNA with some degree of sequence
      specificity, altering the transcription regulation of induced genes. Cells that
      are deficient in nucleotide excision repair, hypersensitive to UV rays, cisplatin
      and conventional alkylating agents, are resistant to ET-743. This is a unique
      property of ET-743 and is of potential importance for the drug activity when
      administered alone or in combination with other drugs. ET-743 showed striking
      antitumour activity against sensitive and resistant human xenografts. The dose
      limiting toxicities in animal models, hepatobiliary events, were of concern, but
      the pattern of the reversibility noted in monkeys and the evidence of a positive
      therapeutic index in tumour-bearing nude mice prompted its clinical development.
      The Phase I programme investigated different schedules of administration, with
      the dose-limiting toxicities being neutropenia and fatigue. As anticipated in the
      preclinical models, reversible non-cumulative transaminitis was a prevalent
      finding from one-third of the maximum tolerated dose level; long-lasting
      objective responses in pretreated resistant patients were noted, including
      consistent efficacy data in mesenchymal tumours. The Phase II data for ET-743
      administered as a single agent has established a clinical role for the compound
      in advanced pretreated soft tissue sarcoma and a promising potential in
      pretreated ovarian and breast cancer. ET-743 combined with other drugs (i.e.,
      cisplatin, paclitaxel or doxorubicin) showed more than additive effects in
      several preclinical systems and initial clinical results (e.g., a combination of
      ET-743 with cisplatin) appear to confirm the preclinical findings. In summary, ET
      743 is a new drug with a novel mode of action, which has demonstrated activity in
      human tumours resistant to the available anticancer drugs. Further comparative
      studies are needed to define the role of ET-743 alone or in combination in cancer
      chemotherapy.

PMID- 14585058
TI  - Fenretinide: a prototype cancer prevention drug.
AB  - Fenretinide (N-4-hydroxyphenylretinamide [4-HPR]) is a synthetic retinoid that
      has been examined in in vitro assays, preclinical animal models and clinical
      trials as a cancer chemopreventive agent. Its pharmacology, toxicity and
      mechanisms of action initially suggested an increased therapeutic index relative
      to native retinoids for the control of tumours of the breast, prostate, bladder,
      colon, cervix and head and neck. Although fenretinide at the doses and schedules
      used in several pivotal Phase II and III clinical trials has not been proven to
      be efficacious in reducing the incidence of cancer or in retarding the
      development of preneoplastic lesions, encouraging observations regarding
      unanticipated preventative activity, such as for ovarian cancer control, have
      arisen from these studies. Research in cancer therapy and the elucidation of
      molecular pathways activated by fenretinide have also yielded clues about how
      this agent might be better used in a prevention setting. Current trials are
      underway to re-examine both dose and schedule of fenretinide administration as
      well as the target tissues of interest. Investigations of potential synergism
      between fenretinide and other candidate chemopreventative molecules with
      complementary mechanisms of action may support future assessments of this
      prototype cancer prevention drug or its newer analogues.

PMID- 14585061
TI  - Ion channels in drug discovery and development.

PMID- 14585060
TI  - Experimental and clinical studies show that the probucol derivative AGI-1067
      prevents vascular growth.
AB  - AGI-1067 is a derivative of probucol that is a promising new development for the
      treatment of restenosis and possibly atherosclerosis. In monkeys fed a high-fat
      diet for 1 year, AGI-1067 prevented the development of atherosclerosis. In these
      monkeys, AGI-1067 lowered plasma levels of low-density lipoprotein (LDL)
      cholesterol and, in contrast to probucol, was capable of increasing high-density
      lipoprotein (HDL)-cholesterol levels. Although AGI1067 did not have marked lipid
      lowering effects in two transgenic mouse models (the LDL-receptor-deficient and
      apolipoprotein-E-deficient models) fed a high-fat chow, it decreased the
      atherosclerotic lesion area in the aorta. In a mouse model of acute inflammation,
      the mRNA for the pro-inflammatory vascular cell adhesion molecule-1 and monocyte
      chemoattractant protein-1 was upregulated and this was inhibited by AGI-1067. AGI
      1067 inhibited the TNF-alpha induction of redox-sensitive inflammatory proteins,
      vascular cell adhesion molecule-1, monocyte chemoattractant protein-1 and
      Eselectin, in cell culture. In addition, AGI-1067 is an antioxidant. In the
      Canadian Antioxidant Restenosis Trial (CART-1) of AGI-1067 in percutaneous
      coronary interventions, AGI-1067 had no effect on LDL-cholesterol but lowered HDL
      cholesterol. At 6 months follow up, the lumen area of the percutaneous coronary
      interventions segments was greater in patients treated with AGI1067 than in
      untreated patients. Restenosis rates were 37.5% in the placebo group and 26% in
      the AGI-1067 group. The lumen area of reference segments was reduced in the
      placebo group but increased with the higher doses of AGI1067. Unlike probucol,
      AGI-1067 did not alter QTc interval.

PMID- 14585062
TI  - Information is care: the need for data to assess the quality of care in UK
      nursing and residential homes.
AB  - Prescribing is the most common medical intervention experienced by elderly
      residents in nursing and residential care homes. However, research would suggest
      that these residents may be subject to poor prescribing, with excessive use of
      some drugs and underprescribing of potentially beneficial drugs. At a more
      fundamental level, there is also evidence that poor medication record-keeping for
      nursing home residents is prevalent in nursing homes, general practice surgeries
      and community pharmacies. This may increase the risk of an adverse drug event.
      Furthermore, there is a lack of data on prescribing in UK nursing homes, which
      militates against assessing the quality of drug use. Consideration needs to be
      given to the structures and processes currently in place in order to promote
      better prescribing outcomes for this vulnerable population.

PMID- 14585063
TI  - Efficacy of antigiardial drugs.
AB  - The flagellated protozoa Giardia duodenalis is the most commonly detected
      parasite in the intestinal tract of humans. Infections with the parasite result
      in diarrhoeal disease in humans and animals, with infants at risk from failure-to
      thrive syndrome. The incidence of giardiasis worldwide may be as high as 1000
      million cases. Current recommended treatments include the nitroheterocyclic drugs
      tinidazole, metronidazole and furazolidone, the substituted acridine, quinacrine,
      and the benzimidazole, albendazole. Paromomycin is also used in some situations,
      and nitazoxanide is proving to be useful. However, treatment failures have been
      reported with all of the common antigiardial agents, and drug resistance to all
      available drugs has been demonstrated in the laboratory. In addition, clinical
      resistance has been reported, including cases where patients failed both
      metronidazole and albendazole treatments. The identification of new antigiardial
      drugs is an important consideration for the future, but maintaining the
      usefulness of the existing drugs is the most cost-effective measure to ensure the
      continued availability of antigiardial drugs.

PMID- 14585064
TI  - Torsade de pointes associated with the administration of intravenous
      haloperidol:a review of the literature and practical guidelines for use.
AB  - Haloperidol is the most commonly used medication for the treatment of delirium
      and psychosis in the critically ill patient. Whilst generally considered to be
      safe, haloperidol has been associated with a number of important cardiovascular
      side effects. The major toxicities include hypotension, cardiac arrhythmias and
      prolongation of the corrected QT (QTc) interval. In particular, torsade de
      pointes, a polymorphic ventricular tachyarrhythmia, has been associated with both
      intravenous and oral haloperidol administration. The management of torsade de
      pointes consists of discontinuation of the possible offending agent(s),
      correction of electrolyte abnormalities, administration of magnesium sulfate and,
      if necessary, overdrive pacing. Although clinicians should be aware of this
      potentially lethal complication of intravenous haloperidol therapy, it should not
      deter clinicians from using intravenous haloperidol to treat acute agitation in
      the critically ill patient with a normal QTc.

PMID- 14585065
TI  - Antihypertensive therapy: special focus on drug interactions.
AB  - Today, the lifetime risk of patients aged 55-65 years to receive antihypertensive
      drugs approaches 60%. Yet, recent trials suggest that hypertension is not
      adequately controlled in the majority of patients. The prevalence of hypertension
      increases with advancing age, as does the prevalence of comorbid conditions and
      the total number of medications taken. Multi-drug therapy, advancing age and
      comorbid conditions are also key risk factors for adverse drug reactions and drug
      interactions. In this review, the authors evaluate the most frequently used
      antihypertensive drugs (diuretics, beta-adrenergic blockers, angiotensin
      converting enzyme inhibitors, calcium channel blockers, angiotensin II receptor
      Type 1 blockers and alpha-adrenergic blockers) with special reference to
      pharmacodynamic and pharmacokinetic drug interactions. As the spectrum of drugs
      prescribed is constantly changing, safety yesterday does not imply safety today
      and safety today does not imply safety tomorrow. Furthermore, therapeutic
      efficacy should not be neglected over concerns regarding drug interactions. Many
      patients are at risk of clinically relevant drug interactions involving
      antihypertensive drugs but, presently, even more patients may be at risk of
      suffering from the consequences of their inadequately treated hypertension. In
      this respect, the authors discuss controversial viewpoints on the overall
      clinical relevance of drug interactions occurring at the level of cytochrome P450
      metabolism.

PMID- 14585066
TI  - Hepatotoxicity of thiazolidinediones.
AB  - Thiazolidinediones are insulin sensitisers now widely used for the treatment of
      Type 2 diabetes mellitus. The initial marketed drug in this class, troglitazone,
      was removed from the market worldwide after approximately 3 years of use due to
      rare but severe hepatotoxicity, which sometimes resulted in liver failure leading
      to the need for liver transplantation, or even death. The unpredictability of
      such liver toxicity made the use of troglitazone highly problematic. Fortunately,
      the two newer drugs in this class, rosiglitazone and pioglitazone, have a much
      larger margin of safety for liver toxicity. Very rare reports of liver toxicity,
      usually milder and reversible, have been seen with these drugs. Therefore, whilst
      pharmacovigilance for hepatotoxicity is probably still warranted, the
      practitioner and patient can be fairly confident that these drugs are safe from a
      liver standpoint. Finally, recent work would suggest that these agents may prove
      useful to reduce hepatic fat in patients with non-alcoholic steatohepatitis, and
      may possibly protect against adverse metabolic consequences and the ultimate
      development of cirrhosis in patients with fatty livers.

PMID- 14585067
TI  - Bleomycin-induced pulmonary toxicity in chemotherapy for testicular cancer.
AB  - Bleomycin is an antibiotic agent with antitumour activity, discovered in 1966 by
      Umezawa et al. Today, bleomycin is commonly used in chemotherapy for various
      tumour types. In testicular cancer especially, bleomycin is one of the key drugs
      in induction chemotherapy. It has the advantage of less myelotoxicity; however,
      its severe and potentially fatal pulmonary toxicity has limited its dose
      intensity. Several clinical trials have focused on eliminating bleomycin from the
      regimen or reducing the bleomycin dose for testicular cancer patients with good
      prognosis. However, the results indicate that bleomycin is still an essential
      component of induction chemotherapy when only three courses are administered.
      This review will focus on bleomycin-induced pulmonary toxicity in chemotherapy
      for testicular cancer, followed by a brief review of recent basic understanding
      of the pathogenesis of lung fibrosis.

PMID- 14585068
TI  - Toxicities of the platinum antineoplastic agents.
AB  - The platinum agents (cisplatin, carboplatin and oxaliplatin) are among the most
      useful anticancer agents available to oncologists. The drugs have the potential
      to produce both mild and more serious side effects. However, in general, the
      platinum agents can be delivered with acceptable toxicity, even when used in
      combination chemotherapy regimens. Furthermore, with appropriate dose
      modifications, the large majority of patients who may benefit from this class of
      cytotoxic pharmaceutical drugs will be able to complete a planned therapeutic
      programme.

PMID- 14585069
TI  - Biologics safety preclinical, clinical and regulatory.
AB  - Biologicals offer particular challenges for all concerned, whether they be
      scientific researchers, profit-oriented companies (including not yet profit
      producing start-ups), public health-focused regulators, physicians, or, most
      importantly, patients. One of the most important of these challenges is safety.
      Hence, this conference was organised by Vision in Business (the trading name of
      Analysis and Networking Ltd) to provide practical solutions and advice for
      comprehensive, effective safety testing. It provided a wide spectrum of
      presentations, ranging from the usefulness of animal models for biologicals
      safety predictions, to an FDA perspective on implications of its recent
      restructuring, to a real-life case study on erythropoietin and pure red cell
      anaemia. For anyone seriously interested in the safety of biologicals, this was a
      very good opportunity to gain an overview of all major aspects of biologicals
      safety, broaden existing expertise and to network with those concerned with these
      issues.

PMID- 14585070
TI  - Apoptosis: Historical perspectives.
AB  - Apoptosis is one of the most widely studied fields in biology and accounts for
      over 2% of all life science publications annually. It plays a fundamental role in
      development, and defects in the regulation of apoptosis are directly implicated
      in numerous well-known diseases including cancer, neurodegenerative disorders,
      tissue atrophy and auto-immune diseases. However, the field of apoptosis has
      humble beginnings and was neglected by biologists for much of its history. This
      chapter reviews the history of research in apoptosis and highlights key
      experiments that have contributed significantly to our current understanding of
      apoptosis. In addition, the topics covered in later chapters are briefly
      introduced.

PMID- 14585071
TI  - Apoptosis and development.
AB  - Apoptosis is an evolutionarily conserved process used by multicellular organisms
      to developmentally regulate cell number or to eliminate cells that are
      potentially detrimental to the organism. The large diversity of regulators of
      apoptosis in mammalian cells and their numerous interactions complicate the
      analysis of their individual functions, particularly in development. The
      remarkable conservation of apoptotic mechanisms across species has allowed the
      genetic pathways of apoptosis determined in lower species, such as the nematode
      Caenorhabditis elegans and the fruitfly Drosophila melanogaster, to act as models
      for understanding the biology of apoptosis in mammalian cells. Though many
      components of the apoptotic pathway are conserved between species, the use of
      additional model organisms has revealed several important differences and
      supports the use of model organisms in deciphering complex biological processes
      such as apoptosis.

PMID- 14585072
TI  - Caspases: the enzymes of death.
AB  - The caspases are a unique family of cysteine proteases, which cleave proteins
      next to an aspartate residue. Among all known mammalian proteases, only the
      serine protease granzyme B has similar substrate specificity. In addition to a
      central role of caspases in the initiation and execution phases of apoptosis,
      these enzymes have some other non-apoptotic functions in living cells. During
      apoptosis, upon activation, caspases cleave specific substrates and thereby
      mediate many of the typical biochemical and morphological changes in apoptotic
      cells, such as cell shrinkage, chromatin condensation, DNA fragmentation and
      plasma-membrane blebbing. Thus, detection of activated caspases can be used as a
      biochemical marker for apoptosis induced by diverse stimuli in many types of
      cells.

PMID- 14585073
TI  - Apoptosis: bombarding the mitochondria.
AB  - Mitochondria play a central role in apoptosis triggered by many stimuli. They
      integrate death signals through Bcl-2 family members and co-ordinate caspase
      activation through the release of apoptogenic factors that are normally
      sequestered in the mitochondrial intermembrane space. The release of these
      proteins is the result of the outer mitochondrial membrane becoming permeable. In
      addition, mitochondria can initiate apoptosis through the production of reactive
      oxygen species.

PMID- 14585074
TI  - Death receptors.
AB  - Death receptors [Fas/Apo-1/CD95, TNF-R1 [tumour necrosis factor (TNF) receptor
      1], DR3 [death receptor 3], TRAIL-R1 [TNF-related apoptosis-inducing ligand
      receptor 1], TRAIL-R2, DR6, p75-NGFR [p75-nerve growth factor receptor], EDAR
      [ectodermal dysplasia receptor]] form a subgroup of the TNF-R superfamily that
      can induce apoptosis (programmed cell death) via a conserved cytoplasmic
      signalling module termed the death domain. Although death receptors have been
      recognized mainly as apoptosis inducers, there is growing evidence that these
      receptors also fulfil a variety of nonapoptotic functions. This review is focused
      on the molecular mechanisms of apoptotic and non-apoptotic death receptor
      signalling in light of the phenotype of mice deficient in the various death
      receptors.

PMID- 14585075
TI  - Guardians of cell death: the Bcl-2 family proteins.
AB  - Apoptosis is mediated through at least three major pathways that are regulated by
      (i) the death receptors, (ii) the mitochondria and (iii) the ER (endoplasmic
      reticulum). In most cells, these pathways are controlled by the Bcl-2 family of
      proteins that can be divided into anti-apoptotic and pro-apoptotic members.
      Although the overall amino acid sequence homology between the family members is
      relatively low, they contain highly conserved domains, referred to as BH (Bcl-2
      homology) domains (BH1-4), that are essential for homo- and hetero-complex
      formation, as well as for their cell-death-inducing capacity. Structural and
      functional analyses revealed that the pro-apoptotic homologues can be subdivided
      into the Bax subfamily and the growing BH3-only subfamily. Recent data indicate
      that BH3-only proteins act as mediators that link various upstream signals,
      including death receptors and DNA damage signalling, to the mitochondrial and the
      ER pathway. This review discusses recent structural and functional insights into
      how these subfamilies promote or inhibit cell-death signals, and how these
      properties may be utilized for development of apoptosis-promoting small
      molecules, e.g. in cancer therapy.

PMID- 14585076
TI  - Oncogenes as regulators of apoptosis.
AB  - Although cancer is a disease that will afflict one out of three people in the
      Western world, when considered at a cellular level, it is a rare clonal event.
      Long-lived organisms, such as humans, have evolved strategies to restrict the
      development of potentially malignant cells, and one such mechanism is the
      coupling of proliferative and apoptotic pathways. Multiple oncogenes have the
      ability to trigger apoptosis when expressed in an inappropriate fashion, and this
      is thought to restrict tumour formation by eliminating potentially malignant
      cells that have acquired a mutation stimulating proliferation. Hence for a tumour
      to arise, in addition to mutations that drive proliferation, mutations that
      prevent apoptosis are also a prerequisite.

PMID- 14585077
TI  - The final step in programmed cell death: phagocytes carry apoptotic cells to the
      grave.
AB  - As cells undergo apoptosis, they are recognized and removed from the body by
      phagocytes. This oft-overlooked yet critical final step in the cell-death
      programme protects tissues from exposure to the toxic contents of dying cells and
      also serves to prevent further tissue damage by stimulating production of anti
      inflammatory cytokines and chemokines. The clearance of apoptotic-cell corpses
      occurs throughout the lifespan of multicellular organisms and is important for
      normal development during embryogenesis, the maintenance of normal tissue
      integrity and function, and the resolution of inflammation. Many of the signal
      transduction molecules implicated in the phagocytosis of apoptotic cells appear
      to have a high degree of evolutionary conservation, and therefore the engulfment
      of apoptotic cells is likely to represent one of the most primitive forms of
      phagocytosis. With the realization that the signals that govern apoptotic-cell
      removal also serve to attenuate inflammation and the immune response, as well as
      initiate signals for tissue repair and remodelling in response to cell death, the
      study of apoptotic cell clearance is a field experiencing a dynamic increase in
      interest and momentum.

PMID- 14585078
TI  - Apoptosis in disease: about shortage and excess.
AB  - The death of cells by apoptosis is a fundamental event in development and the
      maintenance of cell homoeostasis. The other side of the coin, however, is that
      excessive cell death by apoptosis or the lack of apoptosis is often the driving
      force of many diseases. Whereas reduced apoptosis sensitivity is a basic
      characteristic of many tumour cells, accelerated tissue cell death and loss of
      tissue functions is the underlying cause of many auto-immune and inflammatory
      diseases.

PMID- 14585079
TI  - Therapeutic approaches to the modulation of apoptosis.
AB  - The appreciation of the role of apoptosis in the vast majority of diseases
      affecting humans has revolutionized the discovery and development of drugs
      targeting inflammation and oncology. Novel therapeutic approaches to modulate
      disease by regulating apoptosis are currently being tested in preclinical and
      clinical settings. Enthusiasm for some of these therapies is reflected in the
      fact that they have received U.S. Food and Drug Administration approval in record
      time. Approaches include the traditional use of small molecules to target
      specific players in the apoptosis cascade. They also include radical new
      approaches such as using antisense molecules to inhibit production of the Bcl-2
      protein or antibodies that ligate either death receptors, such as TRAIL (tumour
      necrosis factor-related apoptosis-inducing ligand), or the MHC (HLA-DR),
      resulting in the initiation of apoptosis of target cells. Antibodies targeting
      cell-specific antigens are being used in conjunction with radioactive isotopes to
      deliver a more specific chemotherapy, particularly in the case of B-cell
      lymphomas. Other therapies target mitochondria, a key organelle in the apoptosis
      cascade. This diverse range of therapies includes photodynamic therapy, retinoic
      acid and arsenic trioxide, all of which induce apoptosis by generating reactive
      oxygen species. As our understanding of apoptosis increases, further
      opportunities will arise for tailor-made therapies that will result in improved
      clinical outcome without the devastating side effects of current interventions.

PMID- 14585080
TI  - Apoptosis: future perspectives.
AB  - The field of apoptosis has expanded to include research in almost all subject
      areas of cell biology. Despite this growth, there are still many unanswered
      questions, some of which are fundamental to the development of therapeutic
      strategies. Most importantly, the underlying mechanisms involved in conferring
      specificity of apoptotic signals must be determined. This will allow the
      development of treatments to delete injured or transformed cells and minimize
      damage to other tissues. Such information is also necessary to combat
      degenerative diseases, to prevent critical loss of cells. In addition, it would
      be of therapeutic benefit to selectively induce apoptosis in specific cells where
      removal of unwanted cells is required (e.g. tumour cells in malignant tissue or
      inflammatory cells responsible for tissue damage in chronic inflammatory
      disease). Therefore we have to understand how the full complement of signalling
      pathways, and survival and apoptotic proteins determine the end effect of an
      apoptotic signal. Apoptotic cells are known to functionally influence phagocytes
      that ingest them, but little is known of the effect of apoptosis on neighbouring
      cells or of signals generated during the apoptotic process itself. Although the
      processes of mitosis and apoptosis would appear to be diametrically opposed, cell
      cycle proteins are involved in apoptosis, and may be able to influence cell-death
      mechanisms; conversely, proliferation may be caspase-dependent in some cells.
      Further study is necessary to discover how these pathways are interlinked since
      such knowledge would be particularly useful in cancer treatment. The link between
      pathogen-survival strategies and apoptotic mechanisms will also reward further
      work. Viruses, in particular, exploit cellular survival and death pathways for
      replication purposes and may represent a targeting approach for specific
      treatments.

PMID- 14585081
TI  - Lymphocytic hypophysitis: a rare or underestimated disease?
AB  - Lymphocytic hypophysitis (LYH) is an uncommon autoimmune disease in which the
      pituitary gland is infiltrated by lymphocytes, plasma cells and macrophages and
      its function is usually impaired. It has to be suspected in pregnant women and in
      women with recent delivery presenting with hyperprolactinemia, headache, visual
      field alterations and changes of one or more pituitary hormone secretions with
      secondary impairment of related peripheral target glands, especially when
      associated with other autoimmune endocrine or non-endocrine disorders. It can
      also occur less frequently in prepubertal or post-menopausal women and in men.
      Headache, visual field impairment and more rarely diplopia are due to extrasellar
      pituitary enlargement with optic chiasma compression and/or to invasion of
      cavernous sinuses. Among the 'isolated' pituitary hormone deficiencies, ACTH
      deficit is usually the earliest and most frequent hormonal impairment and in rare
      cases can induce an acute secondary hyposurrenalism as the first sign of the
      disease, with high mortality in affected patients. Histopathological findings
      from pituitary biopsy show lymphoplasmacytic infiltrate with lymphoid aggregates
      surrounding atropic acini of pituitary cells; immunohistochemical analysis shows
      numerous mast cells randomly distributed and also localized in the vicinity of
      capillaries, suggesting a possible influence on capillary permeability and
      angiogenesis, thus favoring the inflammatory and immunological aggression against
      pituitary cells. Nuclear magnetic resonance imaging shows uniform sellar floor
      depression and an extrasellar symmetrical pituitary enlargement, usually
      displacing the optic chiasma, which shows a rapid homogeneous enhancement after
      gadolinium also involving the adjacent dura (dural tail). Antipituitary
      antibodies have been detected in several patients with LYH but their role needs
      to be clarified. Since a possible spontaneous remission can occur, a careful
      follow-up is required in subclinical patients without important hyposurrenalism
      or symptomatic extrasellar expansion. Medical (immunosuppressive, replacement and
      antiprolactinemic) and neurosurgical (decompression) treatments are needed in
      clinical symptomatic patients.

PMID- 14585082
TI  - Central effects of the somatotropic system.
AB  - The somatotropic axis interacts with the central nervous system (CNS) on several
      levels. Growth hormone (GH) and insulin-like growth factor-I (IGF-I) receptors
      are expressed in many brain areas including the hippocampus, pituitary and
      hypothalamus. GH and IGF-I can pass the blood-brain barrier by an as yet not
      completely understood mechanism. They can also be produced in the brain and thus
      act via paracrine/autocrine mechanisms. GH and IGF-I are important factors in the
      development and differentiation of the CNS and have protective properties in
      dementia, and in traumatic and ischemic injury of the CNS. An improvement in
      cognitive functioning in GH-deficient patients by GH substitution has been shown.
      Significant results could, however, only be achieved with supraphysiological
      doses. In some studies, a correlation between IGF-I and cognitive function in the
      elderly has been found. GH has an important impact on mood and well-being with GH
      secretory capacity being reduced in depression. Pulsatile GH secretion is closely
      related to slow wave sleep (SWS) with SWS being stimulated by GH releasing
      hormone and rapid eye movement (REM) sleep by GH.

PMID- 14585083
TI  - No association of two Fas gene polymorphisms with Hashimoto's thyroiditis and
      Graves' disease.
AB  - BACKGROUND: Apoptosis is a joint pathogenic process underlying autoimmune thyroid
      disease. Increased programmed cell death in thyrocytes causes hypothyroidism in
      Hashimoto's thyroiditis, whereas in Graves' disease infiltrating lymphocytes
      undergo apoptosis while thyrocytes appear to proliferate under protection of anti
      apoptotic signals. The Fas/Fas ligand cascade represents a major pathway
      initiating apoptosis. Its role in autoimmunity is well studied and genetic
      polymorphisms in gene loci of Fas and its ligand have been shown to be associated
      with autoimmune diseases. OBJECTIVE: Due to the functional relevance of the Fas
      pathway in autoimmune thyroid disease we were interested in the possible
      contribution of polymorphisms in the Fas gene to the genetic risk of thyroid
      autoimmunity, which so far is mainly, but incompletely, attributed to the HLA DQ
      region and polymorphisms in the CTLA-4 gene. DESIGN: We genotyped Caucasian
      families with at least one offspring affected by Hashimoto's thyroiditis (n=95)
      and Graves' disease (n=109) for two Fas gene polymorphisms (g-670 G-->A in the
      promoter region, g-154 C-->T in exon 7). METHODS: Extended transmission
      disequilibrium and chi(2) testing were performed. RESULTS: Neither polymorphism
      alone (P=0.44 and P=0.70) nor the promoter/exon 7 haplotypes (P=0.86) were
      associated with Hashimoto's thyroiditis. No association with Graves' disease was
      observed for the promoter polymorphism (P=0.91) and exon 7 (P=0.65) or the
      promoter/exon 7 haplotypes (P=0.80). CONCLUSION: In summary, our data do not
      suggest any significant contribution of common genetic Fas variants to the
      genetic risk of developing Hashimoto's thyroiditis or Graves' disease.

PMID- 14585085
TI  - Acute plasma glucose increase, but not early insulin response, regulates plasma
      ghrelin.
AB  - OBJECTIVE: The independent role of glucose and insulin in ghrelin regulation is
      still controversial; this is also because in healthy subjects it is difficult to
      isolate the increase of glucose from that of insulin. The aim of this study was
      to discriminate the effect of glucose increase alone and early insulin response
      on plasma ghrelin, comparing ghrelin variation after i.v. glucose between healthy
      subjects and type 2 diabetic (T2DM) subjects, in whom the early insulin response
      to i.v. glucose is abolished. METHODS: Plasma glucose, insulin and ghrelin levels
      were measured 0, 3, 5, 10, 30, 45 and 60 min after a 5 g glucose i.v. bolus in
      seven healthy control subjects and eight T2DM subjects. RESULTS: There were no
      significant differences in body mass index, basal insulin and basal ghrelin
      between T2DM and healthy subjects. Basal glucose levels were higher in T2DM
      subjects than in controls. After i.v. glucose administration, plasma glucose
      increased significantly in both groups and the glucose peak was higher in T2DM
      subjects than in controls (9.67+/-1.25 (s.d.) vs 6.88+/-1.00 mmol/l, P<0.01).
      Insulin increased rapidly in controls, while in T2DM subjects, plasma insulin did
      not rise in the first 10 min. After the glucose bolus, plasma ghrelin showed a
      significant reduction both in controls and in T2DM subjects after 5 min.
      CONCLUSION: These findings indicate that a low-dose i.v. glucose bolus reduces
      ghrelin both in controls and in T2DM subjects and therefore that early insulin
      response does not affect plasma ghrelin.

PMID- 14585084
TI  - Stimulating effect of growth hormone on cytokine release in children.
AB  - OBJECTIVE: The aim of the present study was to investigate the effect of
      exogenously administered GH on serum levels of interleukin (IL)-1beta, IL-2, IL
      12, tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma and their
      relation with IGF-I levels in normal short stature children. DESIGN AND METHODS:
      23 short prepubertal non GH-deficient children (10 females and 13 males) whose
      mean+/-s.d. chronological age was 11.95+/-1.85 Years (from 8.80 to 14.89 Years),
      and mean+/-s.d. bone age was 10.48+/-2.44 Years, were evaluated during a
      somatomedin generation test (human GH 0.1 IU/kg per day for 4 days) to exclude a
      partial GH resistance as the cause of short stature; 34 sex- and age-matched
      healthy subjects were studied as controls. Circulating cytokine values were
      measured in basal conditions in all children, and 12 h following the 4th GH
      subcutaneous injection in the 23 short children only. RESULTS: No significant
      differences were found between short children and controls in basal values of
      serum IGF-I (192.1+/-18.3 and 198.2+/-28.2 ng/ml respectively). In short subjects
      there was a significant increase in serum IGF-I levels after the 4th GH injection
      (from 192.1+/-18.3 ng/ml, i.e. -1.16+/-0.16 standard deviation score (SDS) to
      338.2+/-27.1 ng/ml, i.e. 0.14+/-0.17; P<0.00001). No significant differences were
      found between short children and controls in basal concentrations of serum INF
      gamma (19+/-4 and 26+/-5 mIU/ml respectively), IL-1alpha (24.950+/-3.613 and
      20.896+/-2.778 pg/ml respectively), IL-2 (3.945+/-1.209 and 4.794+/-0.562 pg/ml
      respectively), IL-12 (1.093+/-0.269 and 1.976+/-0.596 pg/ml respectively), and
      TNF-alpha (1.794+/-0.559 and 2.188+/-0.346 pg/ml respectively). Likewise, a
      significant increase was found in serum INF-gamma (before 19+/-4 and after four
      GH injections 185+/-57 mIU/ml respectively; P<0.008), IL-1beta (24.950+/-3.613 to
      43.339+/-5.431 pg/ml respectively; P<0.0001), IL-2 (3.945+/-1.209 to 9.165+/
      2.331 pg/ml respectively; P<0.003), IL-12 (1.093+/-0.269 to 3.724+/-0.637 pg/ml
      respectively; P<0.0007) and TNF-alpha (1.794+/-0.559 to 9.266+/-3.066 pg/ml
      respectively; P<0.01). CONCLUSIONS: Cytokine release can be affected by short
      term GH administration in normal children indicating a direct influence of GH on
      the immune system.

PMID- 14585086
TI  - The effects of human leptin fragment(126-140) on pituitary functions in man.
AB  - OBJECTIVE: The effects of human leptin fragment(126-140) on pituitary function in
      eight healthy, non-obese men were studied. METHODS AND DESIGN: The effects of the
      fragment on spontaneous secretion of pituitary hormones and endogenous leptin, as
      well as on GHRH-induced GH secretion were examined. RESULTS: After the
      administration of the fragment (50 microg i.v. for 150 min), the mean nadir value
      and 45 min value were significantly lower than that of the control study.
      Endogenous leptin levels did not decrease significantly following the
      administration of the leptin fragment. Other pituitary hormones were not affected
      by the fragment. The area under the curve of the GH response to GHRH(1-44)NH(2)
      (10 microg, i.v. from 0 to 75 min) was also significantly inhibited by the
      combined administration of the leptin fragment (100 microg i.v. from -30 to 75
      min) (P<0.001). Three subjects were re-examined with larger doses of the leptin
      fragment (200-400 microg), and even greater GH suppression was observed.
      CONCLUSIONS: These results indicate that human leptin fragment(126-140) has an
      inhibitory role in GH secretion, since when administered exogenously this
      fragment significantly suppressed spontaneous and, in a dose-response manner,
      GHRH-induced GH secretion. Clear effects of the fragment on other pituitary
      hormones and an inhibitory effect on endogenous leptin secretion were not
      observed in this study.

PMID- 14585087
TI  - Insulin levels measured with an insulin-specific assay in patients with fasting
      hypoglycaemia related to endogenous hyperinsulinism.
AB  - OBJECTIVE: The finding of insulin levels above a minimum threshold at the time of
      symptomatic hypoglycaemia is crucial in the diagnosis of endogenous
      hyperinsulinism. The aim of this study was to evaluate insulin levels at the time
      of hypoglycaemia with an insulin-specific assay in such patients. DESIGN AND
      METHODS: We measured insulin levels in 15 patients with fasting hypoglycaemia
      related to endogenous hyperinsulinism using an insulin-specific immunoradiometric
      assay (IRMA) without any significant cross-reaction with intact proinsulin.
      RESULTS: Insulin levels were below 6 mIU/l in all the samples taken at the time
      of symptomatic hypoglycaemia in 6/15 patients, and in some of the samples in
      three patients; insulin levels were below 3 mIU/l in samples from 5 patients. C
      peptide levels were above 0.6 ng/ml in all these samples. The lowest proinsulin
      level was 35 pmol/l. Insulin levels were measured with a less specific RIA (40%
      cross-reaction with proinsulin) in 8/15 patients and were above 6 mIU/l in all
      samples in seven patients, and all but one sample in the 8th patient. Mean
      concomitant C-peptide and insulinoma size were lower in those patients with
      insulin-IRMA levels below 6 mIU/l. CONCLUSION: Symptomatic hypoglycaemia below
      0.45 g/l can result from insulin levels below 6 or even 3 mIU/l; lower insulin
      levels and secretion could be observed preferentially in small insulinomas. If an
      insulin assay devoid of any significant cross-reaction with intact proinsulin is
      employed, measuring C-peptide (and/or proinsulin) levels at the time of
      symptomatic hypoglycaemia is mandatory to make the diagnosis of endogenous
      hyperinsulinism.

PMID- 14585088
TI  - Absence of exercise-induced variations in adiponectin levels despite decreased
      abdominal adiposity and improved insulin sensitivity in type 2 diabetic men.
AB  - OBJECTIVE: We investigated the effect of an intensive training program on fasting
      leptin and adiponectin levels. METHODS: Sixteen middle-aged men with type 2
      diabetes were randomly assigned to either a training or control group. The
      training program consisted of 8 weeks of supervised endurance exercise (75%
      VO(2peak), 45 min) twice a week, with intermittent exercise (five 2 min exercises
      at 85% VO(2peak) separated by 3 min exercises at 50% VO(2peak)) once a week, on
      an ergocycle. RESULTS: Training decreased abdominal fat by 44%, increased mid
      thigh muscle cross-sectional area by 24%, and improved insulin sensitivity by 58%
      without significant change in body weight. Compared with controls, no significant
      variation in leptin or adiponectin levels was observed. However, in the trained
      group, change in adiponectin correlated with change in body weight (Spearman rank
      correlation, r(s):-0.76, P=0.03) but not with insulin sensitivity or abdominal
      adiposity variations. CONCLUSIONS: An 8 week intensive training program inducing
      a marked reduction in abdominal fat and increase in insulin sensitivity does not
      affect adiponectin and leptin levels in men with type 2 diabetes.

PMID- 14585089
TI  - Pubertal course of persistently short children born small for gestational age
      (SGA) compared with idiopathic short children born appropriate for gestational
      age (AGA).
AB  - OBJECTIVE: Few data are available on the pubertal development of children born
      small for gestational age (SGA) who fail to show catch-up growth. DESIGN: A
      longitudinal analysis compared the pubertal course of persistently short children
      born SGA compared to children with idiopathic short stature who were appropriate
      for gestational age (AGA). One hundred and twenty-eight short children (height
      SDS<-1.7), including 76 (31 boys) born SGA and 52 (22 boys) born AGA, were
      regularly followed from early childhood to completion of puberty. RESULTS:
      Puberty was attained at normal age (10.5-14 Years in boys, 9.5-13 Years in girls)
      for most children in both the SGA and AGA groups (boys, 80% and 77%; girls, 76%
      and 78% respectively). The duration of puberty was similar in the SGA and AGA
      groups. Menarche occurred at normal age range but was significantly earlier in
      the SGA girls (P<0.01 by ANOVA). Despite the similar total pubertal growth, the
      patterns of growth differed significantly: SGA group - accelerated growth and
      bone maturation rates from onset of puberty with peak height velocity at Tanner
      stages 2-3, followed by a decelerated growth rate and earlier fusion of the
      epiphyses; AGA group - steady progression of bone elongation and maturation
      throughout puberty (pubertal growth, P<0.05 in both sexes; bone maturation,
      P<0.001 in both sexes). Final height in the SGA group was compromised compared
      with their target height (P<0.001). CONCLUSION: Children born SGA have a normal
      pubertal course with a distinct pubertal growth pattern. This pattern may
      represent an altered regulation of their growth modalities.

PMID- 14585091
TI  - Prevalence of polycystic ovaries in women with androgenic alopecia.
AB  - OBJECTIVE: Although androgenic alopecia is recognised to be a symptom of
      polycystic ovary syndrome (PCOS), it is not known whether polycystic ovaries
      (PCO) and associated endocrine abnormalities are present in patients who present
      with alopecia as a primary complaint. We therefore set out to determine the
      strength of the association between androgenic alopecia and PCO. We examined the
      prevalence of ultrasound-based polycystic ovarian morphology and associated
      clinical and biochemical features in a large multiethnic group of women whose
      presenting complaint was of alopecia, and in a control group. SUBJECTS AND
      METHODS: We studied 89 women of mixed ethnic origin with androgenic alopecia and
      compared them to 73 control women. A detailed history was taken, anthropometry
      was performed and assessment of body-hair distribution was made. The presence of
      PCO was established by pelvic ultrasound scan. Serum gonadotrophins,
      testosterone, androstenedione, dihydrotestosterone and sex hormone binding
      globulin concentrations were measured. RESULTS: Women with alopecia had a higher
      prevalence of PCO and hirsutism than the control population (PCO: 67% vs 27%,
      P<0.00001; hirsutism: 21% vs 4%, P=0.003). Women with alopecia (with or without
      PCO) had higher testosterone, androstenedione and free androgen index than
      controls, even though few had frankly abnormal androgens. CONCLUSIONS: These
      findings confirm an association between androgenic alopecia and PCO, and other
      symptoms of hyperandrogenaemia. Thus most women who present with androgenic
      alopecia as their primary complaint also have PCO and have indices of abnormal
      androgen production. Since PCO is a well known risk factor for development of
      type 2 diabetes, this association has important implications for long-term
      management.

PMID- 14585090
TI  - Expression of betaglycan in pregnant tIssues throughout gestation.
AB  - BACKGROUND: Betaglycan is a membrane-anchored proteoglycan involved in mediating
      the passage of transforming growth factor-beta (TGF-beta), inhibin and activin
      activities into cells. TGF-beta and inhibin-related proteins are growth factors
      that are expressed by several tIssues and in pregnancy. They have a function in
      modulating the growth, differentiation and invasion of the placental trophoblast.
      OBJECTIVE: To evaluate whether betaglycan is expressed by intrauterine tissues
      throughout gestation. DESIGN AND METHODS: Expression of betaglycan mRNA and
      protein was evaluated (by RT-PCR and immunohistochemistry, respectively) in
      trophoblast, decidua and fetal membranes collected during the first (n=6 elective
      terminations of pregnancy, between 8 and 12 gestational weeks) and third (n=6
      elective caesarean sections, between 39 and 40 weeks) trimesters of pregnancy.
      RESULTS: Betaglycan mRNA was expressed by all gestational tIssues, independently
      of gestational age. Immunoreactive protein was found in decidual cells and in
      some chorionic, but not epithelial, amniotic cells. With respect to the placental
      localization, syncytiotrophoblast, but not cytotrophoblast, cells were
      intensively stained both in the placental bed and in the villous trophoblast, and
      in some cells within the stroma of terminal villi, of the first and third
      trimesters of pregnancy. Immunoreactive betaglycan was demonstrated in the
      endothelial cells of decidual vessels in both the first and third trimesters of
      pregnancy, whereas endothelial cells of fetal blood vessels in the villous were
      clearly represented only in first trimester samples, not in those of term
      placenta. CONCLUSIONS: Betaglycan mRNA and peptide are expressed by the
      trophoblast, the decidua and the fetal membranes, but the localization of the
      peptide in vessel walls is dependent on gestational age.

PMID- 14585092
TI  - Thyroid over-expression of type 1 and type 2 deiodinase may account for the
      syndrome of low thyroxine and increasing triiodothyronine during propylthiouracil
      treatment.
AB  - Although propylthiouracil inhibits type 1 deiodinase, leading to a more rapid
      fall in triiodothyronine (T(3)) than thyroxine (T(4)) levels in patients treated
      for hyperthyroidism, we report a patient with Graves' disease whose free T(3)
      paradoxically rose during such treatment, despite low free T(4) levels and
      increasing doses of propylthiouracil. A similar response has previously been
      associated with high levels of thyroid stimulating antibodies, but it has been
      unclear why there should be a dichotomy in the circulating thyroid hormone
      profile. Thyroid tIssue from our patient contained very high levels of type 1
      and, especially, type 2 deiodinase, in contrast to other patients treated with
      Graves' disease, which were most likely secondary to high levels of thyroid
      stimulating antibodies. This unusual response to propylthiouracil is important to
      recognise therapeutically, and represents a further situation in which abnormal
      expression of deiodinase enzymes has clinical significance.

PMID- 14585094
TI  - Functional in vitro studies on the role and regulation of interleukin-6 in human
      somatotroph pituitary adenomas.
AB  - OBJECTIVE: Interleukin-6 (IL-6), a member of the gp130 cytokine family, is
      considered to be an important modulator of function and growth in endocrine
      anterior pituitary cells. In pituitary adenomas, where IL-6 is often produced by
      the tumour cells, it is thought to be involved in pituitary adenoma
      pathophysiology via autocrine/paracrine mechanisms. METHODS: We have studied in
      primary cell cultures of human somatotroph adenomas whether IL-6 stimulates
      growth hormone secretion and whether intratumoral IL-6 is affected by various IL
      6-regulating factors. RESULTS: Interleukin-6 stimulated GH secretion in 10 out of
      11 somatotroph adenoma cultures (1.4- to 6.5-fold above basal levels). In
      comparative studies the GH-stimulatory potency of IL-6 was identical, or even
      stronger, than that of GHRH. In eight out of 11 adenoma cell cultures, IL-6
      production was observed. This suggests that GH production might be stimulated by
      IL-6 in an autocrine/paracrine manner in these tumours. Dexamethasone strongly
      inhibited basal IL-6 secretion in all IL-6-producing adenoma cell cultures,
      whereas the IL-6 inhibitory or stimulatory action of other factors (octreotide,
      transforming growth factor-beta1, insulin-like growth factor-I, pituitary
      adenylate cyclase-activating peptide and oestradiol) were heterogeneous in the
      different adenomas. Only transforming growth factor-alpha consistently stimulated
      IL-6 secretion in all of the adenomas studied. CONCLUSIONS: Intratumoral IL-6,
      which is differently regulated by various factors, might contribute to excessive
      GH production in the majority of somatotroph adenomas.

PMID- 14585095
TI  - Screening of silent myocardial ischaemia in type 2 diabetic patients with
      additional atherogenic risk factors: applicability and accuracy of the exercise
      stress test.

PMID- 14585093
TI  - The investigation of galectin-3 in diseases of the thyroid gland.
AB  - OBJECTIVE: Malignant tumors of the thyroid gland exhibit a variety of
      histopathologies and clinical behavior. Immune markers are gaining more and more
      importance in diagnostic pathology, especially in the differential diagnostics
      and in the grading of thyroid gland tumors. DESIGN: The Authors investigated the
      immunohistochemical reaction of galectin-3 (gal3) in patients with various
      thyroid gland diseases. They tested the diagnostic value of gal3 in determining
      the benign or malignant nature of various lesions, especially in lesions of
      follicular origin, because previous results have indicated nearly 100%
      specificity and sensitivity in this regard. METHODS: Gal3 immunoperoxidase
      reaction was carried out on 91 sections of thyroid gland samples fixed in
      formalin and embedded in paraffin. RESULTS: While gal3 expressed itself strongly
      and diffusely in papillary carcinomas (19 of 20 cases), in other malignant
      lesions it showed weaker, focal or variable positivity. Focal positivity was
      found in four of 19 follicular adenomas, and negativity was found in three of 10
      follicular carcinomas. In all cases of inflammation a focal positivity was
      observed (eight of eight cases). All nodular goiter and normal thyroid tIssue
      were negative (25 of 25 cases). CONCLUSIONS: Based on our results, the gal3
      immunohistochemical reaction seems to be reliable in the diagnosis of papillary
      carcinomas. However, in the case of solitary thyroid nodules and follicular
      lesions, although it is still a useful supplementary marker, it is not of
      absolute value (as stated in previous studies) in determining whether a tumor is
      benign or malignant.

PMID- 14585097
TI  - Is long-term bisphosphonate administration associated with significantly
      increased circulating parathormone levels in patients with multiple myeloma?

PMID- 14585098
TI  - Functional polypeptides can be synthesized from human mitochondrial transcripts
      lacking termination codons.
AB  - The human mitochondrial genome (mtDNA) is a small, circular DNA duplex found in
      multi-copy in the mitochondrial matrix. It is almost fully transcribed from both
      strands to produce large polycistronic RNA units that are processed and matured.
      The 13 mtDNA-encoded polypeptides are translated from mt-mRNAs that have been
      matured by polyadenylation of their free 3'-termini. A patient with clinical
      features consistent with an mtDNA disorder was recently shown to carry a
      microdeletion, resulting in the loss of the termination codon for MTATP6 and in
      its juxtaposition with MTCO3. Cell lines from this patient exhibited low steady
      state levels of RNA14, the bi-cistronic transcript encoding subunits 6 and 8 of
      the F(o)F(1)-ATP synthase, complex V, consistent with a decreased stability.
      Recent reports of 'non-stop' mRNA decay systems in the cytosol have failed to
      determine the fate of gene products derived from transcripts lacking termination
      codons, although enhanced decay clearly required the 'non-stop' transcripts to be
      translated. We wished to determine whether functional translation products could
      still be expressed from non-stop transcripts in the human mitochondrion. Although
      a minor defect in complex V assembly was noted in the patient-derived cell lines,
      the steady-state level of ATPase 6 was similar to controls, consistent with the
      pattern of de novo mitochondrial protein synthesis. Moreover, no significant
      difference in ATP synthase activity could be detected. We conclude that, in the
      absence of a functional termination codon, although mitochondrial transcripts are
      more rapidly degraded, they are also translated to generate stable polypeptides
      that are successfully integrated into functional enzyme complexes.

PMID- 14585099
TI  - The parsley plastocyanin-turnip cytochrome f complex: a structurally distorted
      but kinetically functional acidic patch.
AB  - In general, inter-protein electron transfer proceeds via the formation of
      transient complexes. The initial stage of the interaction between plastocyanin
      (PCu) and cytochrome f (cyt f ) from plants is mediated by complementary
      electrostatics. Given the diffuse nature of its acidic patch, parsley PCu is an
      atypical example of a plant PCu. The interaction of this PCu with turnip cyt f
      was investigated by stopped-flow kinetics, NMR spectroscopy and protein-docking
      simulations. We show that, despite the altered acidic patch, parsley PCu is as
      efficient as spinach PCu in accepting electrons from cyt f, over the
      physiological range of ionic strength. At high ionic strength, the rate constant
      for the reaction of cyt f with parsley PCu is twice that of the spinach protein.
      This difference in reactivity is attributed to variations in the hydrophobic
      patch of parsley PCu. The results of NMR studies and protein-docking simulations
      indicate that parsley PCu and its spinach analogue adopt different orientations
      in their complexes with cyt f.

PMID- 14585103
TI  - Peripheral monocytes from diabetic patients with coronary artery disease display
      increased bFGF and VEGF mRNA expression.
AB  - BACKGROUND: Macrophages can produce vascular endothelial growth factor (VEGF) in
      response to hypoxia, transforming growth factor beta1 (TGF-beta1), angiotensin
      II, basic fibroblast growth factor (bFGF), and interleukin-1. These factors have
      been found in the serum of coronary artery disease (CAD) patients as well as in
      atherosclerotic lesions. The aim of the present study was to test the hypothesis
      that the expression of VEGF, TGF-beta1 and bFGF in peripheral monocytes and
      lymphocytes is related to CAD. METHODS: Human Mononuclear cells and lymphocytes
      from peripheral blood were isolated from 53 donors undergoing angiography.
      Seventeen were found to be healthy and 36 were diagnosed with CAD. The respective
      mRNAs were extracted and quantified. RESULTS: The statistical analysis revealed a
      significant increase of the basal level expression for macrophage VEGF and bFGF
      in the CAD SA (stable angina) patient group compared to the noCAD (control) (p =
      0.041 and p = 0.022 respectively) and CAD UA (unstable angina) (p = 0.024 and p =
      0.005 respectively) groups, which was highly dependent on the diabetic status of
      the population. Furthermore, we demonstrated with an in vitro cell culture model
      that the levels of VEGF and bFGF in monocytes of healthy donors are not affected
      by short term exposure to increased glucose levels (usually observed in the
      diabetic patients) and/or statin. CONCLUSION: Our findings display a
      statistically significant association of the increased VEGF and bFGF levels in
      peripheral monocytes, with stable angina and diabetes in coronary artery disease.
      The results give new insight to CAD and the impaired collateral vessel formation
      in diabetics.

PMID- 14585101
TI  - Variation in diabetes care by age: opportunities for customization of care.
AB  - BACKGROUND: The quality of diabetes care provided to older adults has usually
      been judged to be poor, but few data provide direct comparison to other age
      groups. In this study, we hypothesized that adults age 65 and over receive lower
      quality diabetes care than adults age 45-64 years old. METHODS: We conducted a
      cohort study of members of a health plan cared for by multiple medical groups in
      Minnesota. Study subjects were a random sample of 1109 adults age 45 and over
      with an established diagnosis of diabetes using a diabetes identification method
      with estimated sensitivity 0.91 and positive predictive value 0.94. Survey data
      (response rate 86.2%) and administrative databases were used to assess diabetes
      severity, glycemic control, quality of life, microvascular and macrovascular
      risks and complications, preventive care, utilization, and perceptions of
      diabetes. RESULTS: Compared to those aged 45-64 years (N = 627), those 65 and
      older (N = 482) had better glycemic control, better health-related behaviors, and
      perceived less adverse impacts of diabetes on their quality of life despite
      longer duration of diabetes and a prevalence of cardiovascular disease twice that
      of younger patients. Older patients did not ascribe heart disease to their
      diabetes. Younger adults often had explanatory models of diabetes that interfere
      with effective and aggressive care, and accessed care less frequently. Overall,
      only 37% of patients were simultaneously up-to-date on eye exams, foot exams, and
      glycated hemoglobin (A1c) tests within one year. CONCLUSION: These data
      demonstrate the need for further improvement in diabetes care for all patients,
      and suggest that customisation of care based on age and explanatory models of
      diabetes may be an improvement strategy that merits further evaluation.

PMID- 14585105
TI  - Potential role of interleukin-1 at the peri-ovulation stage in a species of
      placental viviparous reptile, the three-toed skink, Chalcides chalcides
      (Squamata: Scincidae).
AB  - We recently showed that interleukin-1 (IL-1) is secreted by the placenta of a
      species of squamate reptile, the three-toed skink, Chalcides chalcides. In this
      study, we used immunohistochemical techniques to investigate the expression of IL
      1 (in the two isoforms, IL-1alpha and IL-1beta) and its specific membrane
      receptor IL-1 RtI in uterine oviduct during the peri-implantation period. We
      found that both IL-1 and its receptor were expressed in uterine tissues before
      and after ovulation (in the pre-ovulatory stage, even before the yolk had formed
      in the ovary). However, while IL-1alpha was mostly localized in the uterine
      mesenchyme tissue, IL-1beta and IL-1RtI were present in the uterine epithelium.
      Our data provide a further comparison between the reproduction of mammals and
      squamate reptiles.

PMID- 14585104
TI  - Fast renal trapping of porcine luteinizing hormone (pLH) shown by 123I
      scintigraphic imaging in rats explains its short circulatory half-life.
AB  - BACKGROUND: Sugar moieties of gonadotropins play no primary role in receptor
      binding but they strongly affect their circulatory half-life and consequently
      their in vivo biopotencies. In order to relate more precisely hepatic trapping of
      these glycoproteic hormones with their circulatory half-life, we undertook a
      comparative study of the distribution and elimination of porcine LH (pLH) and
      equine CG (eCG) which exhibit respectively a short and a long half-life. This was
      done first by following half-lives of pLH in piglets with hepatic portal
      circulation shunted or not. It was expected that such a shunt would enhance the
      short half-life of pLH. Subsequently, scintigraphic imaging of both 123I-pLH and
      123I-eCG was performed in intact rats to compare their routes and rates of
      distribution and elimination. METHODS: Native pLH or eCG was injected to normal
      piglets and pLH was tested in liver-shunted anaesthetized piglet. Blood samples
      were recovered sequentially over one hour time and the hormone concentrations
      were determined by a specific ELISA method. Scintigraphic imaging of 123I-pLH and
      123I-eCG was performed in rats using a OPTI-CGR gamma camera. RESULTS: In liver
      shunted piglets, the half-life of pLH was found to be as short as in intact
      piglets (5 min). In the rat, the half-life of pLH was also found to be very short
      (3-6 min) and 123I-pLH was found to accumulate in high quantity in less than 10
      min post injection at the level of kidneys but not in the liver. 123I-eCG didn't
      accumulate in any organ in the rats during the first hour, plasma concentrations
      of this gonadotropin being still elevated (80%) at this time. CONCLUSION: In both
      the porcine and rat species, the liver is not responsible for the rapid
      elimination of pLH from the circulation compared to eCG. Our scintigraphic
      experiments suggest that the very short circulatory half-life of LH is due to
      rapid renal trapping.

PMID- 14585106
TI  - Variation of malaria transmission and morbidity with altitude in Tanzania and
      with introduction of alphacypermethrin treated nets.
AB  - BACKGROUND: Highland areas with naturally less intense malaria transmission may
      provide models of how lowland areas might become if transmission was permanently
      reduced by sustained vector control. It has been argued that vector control
      should not be attempted in areas of intense transmission. METHODS: Mosquitoes
      were sampled with light traps, pyrethrum spray and window exit traps. They were
      tested by ELISA for sporozoites. Incidence of malaria infection was measured by
      clearing existing infections from children with chlorproguanil-dapsone and then
      taking weekly blood samples. Prevalence of malaria infection and fever, anaemia
      and splenomegaly were measured in children of different age groups. All these
      measurements were made in highland and lowland areas of Tanzania before and after
      provision of bednets treated with alphacypermethrin. RESULTS: Entomological
      inoculation rates (EIR) were about 17 times greater in a lowland than a highland
      area, but incidence of infection only differed by about 2.5 times. Malaria
      morbidity was significantly less prevalent in the highlands than the lowlands.
      Treated nets in the highlands and lowlands led to 69-75% reduction in EIR.
      Malaria morbidity showed significant decline in younger children at both
      altitudes after introduction of treated nets. In children aged 6-12 the decline
      was only significant in the highlands CONCLUSIONS: There was no evidence that the
      health benefits to young children due to the nets in the lowlands were "paid for"
      by poorer health later in life. Our data support the idea of universal provision
      of treated nets, not a focus on areas of natural hypo-endemicity.

PMID- 14585108
TI  - What can we learn from facilitator and student perceptions of facilitation skills
      and roles in the first year of a problem-based learning curriculum?
AB  - BACKGROUND: The small group tutorial is a cornerstone of problem-based learning.
      By implication, the role of the facilitator is of pivotal importance. The present
      investigation canvassed perceptions of facilitators with differing levels of
      experience regarding their roles and duties in the tutorial. METHODS: In January
      2002, one year after problem-based learning implementation at the Nelson R.
      Mandela School of Medicine, facilitators with the following experience were
      canvassed: trained and about to facilitate, facilitated once only and facilitated
      more than one six-week theme. Student comments regarding facilitator skills were
      obtained from a 2001 course survey. RESULTS: While facilitators generally agreed
      that the three-day training workshop provided sufficient insight into the
      facilitation process, they become more comfortable with increasing experience.
      Many facilitators experienced difficulty not providing content expertise. Again,
      this improved with increasing experience. Most facilitators saw students as
      colleagues. They agreed that they should be role models, but were less
      enthusiastic about being mentors. Students were critical of facilitators who were
      not up to date with curriculum implementation or who appeared disinterested.
      While facilitator responses suggest that there was considerable intrinsic
      motivation, this might in fact not be the case. CONCLUSIONS: Even if they had
      facilitated on all six themes, facilitators could still be considered as novices.
      Faculty support is therefore critical for the first few years of problem-based
      learning, particularly for those who had facilitated once only. Since student and
      facilitator expectations in the small group tutorial may differ, roles and duties
      of facilitators must be explicit for both parties from the outset.

PMID- 14585109
TI  - Re-emerging syphilis: a detrended correspondence analysis of the behaviour of HIV
      positive and negative gay men.
AB  - BACKGROUND: Recent syphilis outbreaks in the UK have raised serious concerns
      about the sexual health of the population. Moreover, syphilis appears more likely
      to facilitate HIV transmission than any other sexually transmitted infection
      (STI). METHODS: The sexual and other risk behaviour of a sample of HIV positive
      and negative gay men with and without syphilis was subjected to a detrended
      correspondence analysis (DCA). RESULTS: A DCA plot was used to illustrate
      similarity of individuals in terms of their behaviours, regardless of their
      infection status. The majority of those with syphilis (78%; 18/23) fell into a
      high-risk group with more partners, and use of anonymous sex venues and drugs
      during sex. However, 16% of uninfected controls (8/49) and 62% of HIV positive
      individuals without syphilis (8/13) also fell into this high-risk group.
      CONCLUSIONS: Using a statistical technique that is novel for this type of
      investigation, we demonstrate behavioural overlaps between syphilis-infected
      individuals in an ongoing UK outbreak and uninfected HIV positive and negative
      controls. Given the high-risk behaviour of a significant proportion of uninfected
      individuals, ongoing transmission of syphilis and HIV in this population seems
      likely.

PMID- 14585107
TI  - A randomised trial of an Internet weight control resource: the UK Weight Control
      Trial [ISRCTN58621669].
AB  - BACKGROUND: Obesity treatment is notoriously unsuccessful and one of the barriers
      to successful weight loss reported by patients is a lack of social support. The
      Internet offers a novel and fast approach to the delivery of health information,
      enabling 24-hour access to help and advice. However, much of the health
      information available on the Internet is unregulated or not written by qualified
      health professionals to provide unbiased information. The proposed study aims to
      compare a web-based weight loss package with traditional dietary treatment of
      obesity in participants. The project aims to deliver high quality information to
      the patient and to evaluate the effectiveness of this information, both in terms
      of weight loss outcomes and cost-effectiveness. METHODS: This study is a
      randomised controlled trial of a weight loss package against usual care provided
      within General Practice (GP) surgeries in Leeds, UK. Participants will be
      recruited via posters placed in participating practices. A target recruitment
      figure of 220 will enable 180 people to be recruited (allowing for 22% dropout).
      Participants agreeing to take part in the study will be randomly allocated using
      minimisation to either the intervention group, receiving access to the Internet
      site, or the usual care group. The primary outcome of the study will be the
      ability of the package to promote change in BMI over 6 and 12 months compared
      with traditional treatment. Secondary outcomes will be the ability of the
      Internet package to promote change in reported lifestyle behaviours. Data will be
      collected on participant preferences, adherence to treatment, health care use and
      time off work. Difference in cost between groups in provision of the intervention
      and the cost of the primary outcome will also be estimated. CONCLUSION: A
      positive result from this study would enhance the repertoire of treatment
      approaches available for the management of obesity. A negative result would be
      used to inform the research agenda and contribute to redefining future strategies
      for tackling obesity.

PMID- 14585111
TI  - Aerosol therapy: assume nothing and require data.

PMID- 14585112
TI  - Blood gases, weaning, and extubation.

PMID- 14585110
TI  - The renin-angiotensin-aldosterone system in patients with depression compared to
      controls--a sleep endocrine study.
AB  - BACKGROUND: Hypercortisolism as a sign of hypothamamus-pituitary-adrenocortical
      (HPA) axis overactivity and sleep EEG changes are frequently observed in
      depression. Closely related to the HPA axis is the renin-angiotensin-aldosterone
      system (RAAS) as 1. adrenocorticotropic hormone (ACTH) is a common stimulus for
      cortisol and aldosterone, 2. cortisol release is suppressed by mineralocorticoid
      receptor (MR) agonists 3. angiotensin II (ATII) releases CRH and vasopressin from
      the hypothalamus. Furthermore renin and aldosterone secretion are synchronized to
      the rapid eyed movement (REM)-nonREM cycle. METHODS: Here we focus on the
      difference of sleep related activity of the RAAS between depressed patients and
      healthy controls. We studied the nocturnal plasma concentration of ACTH,
      cortisol, renin and aldosterone, and sleep EEG in 7 medication free patients with
      depression (1 male, 6 females, age: (mean +/-SD) 53.3 +/- 14.4 yr.) and 7 age
      matched controls (2 males, 5 females, age: 54.7 +/- 19.5 yr.). After one night of
      accommodation a polysomnography was performed between 23.00 h and 7.00 h. During
      examination nights blood samples were taken every 20 min between 23.00 h and 7.00
      h. Area under the curve (AUC) for the hormones separated for the halves of the
      night (23.00 h to 3.00 h and 3.00 h to 7.00 h) were used for statistical
      analysis, with analysis of co variance being performed with age as a covariate.
      RESULTS: No differences in ACTH and renin concentrations were found. For
      cortisol, a trend to an increase was found in the first half of the night in
      patients compared to controls (p < 0.06). Aldosterone was largely increased in
      the first (p < 0.05) and second (p < 0.01) half of the night. Cross correlations
      between hormone concentrations revealed that in contrast to earlier findings,
      which included only male subjects, in our primarily female sample, renin and
      aldosterone secretion were not coupled and no difference between patients and
      controls could be found, suggesting a gender difference in RAAS regulation. No
      difference in conventional sleep EEG parameters were found in our sample.
      CONCLUSION: Hyperaldosteronism could be a sensitive marker for depression.
      Further our findings point to an altered renal mineralocorticoid sensitivity in
      patients with depression.

PMID- 14585113
TI  - Alpha-1 antitrypsin deficiency: an under-recognized but important issue for
      respiratory therapists.

PMID- 14585114
TI  - The delivery of chlorofluorocarbon-propelled versus hydrofluoroalkane-propelled
      beclomethasone dipropionate aerosol to the mechanically ventilated patient: a
      laboratory study.
AB  - We describe a laboratory investigation comparing the delivery of
      chlorofluorocarbon (CFC)- and hydrofluoroalkane (HFA)-formulated beclomethasone
      dipropionate (BDP) by metered-dose inhaler and holding chamber (AeroChamber HC
      MV) in a simulation of a mechanically ventilated adult patient. METHODS: We
      equipped each HC MV (n = 5) with an 8.0 mm diameter endotracheal tube (ETT),
      locating the HC MV in the inspiratory limb of a breathing circuit linked to a
      mechanical ventilator set to simulate tidal breathing at tidal volume = 830 mL,
      respiratory rate = 15 breaths/min, inspiratory-expiratory ratio of 1:2.1, peak
      inspiratory pressure = 20 cm H(2)O. Temperature and humidity settings were 35+/-1
      degrees C and 100% relative humidity (close to body conditions). We compared
      delivery of 5-actuations of CFC- and HFA-BDP (both 50 microg/actuation),
      measuring total emitted mass captured by a filter at the distal end of the ETT.
      In a separate study, we inserted the distal end of the ETT within the entry cone
      of a cascade impactor so that the aerosol particle size distribution could be
      determined with the circuit at similar environmental conditions as described
      previously. We made benchmark measurements with circuit temperature and humidity
      at room ambient conditions (21+/-1 degrees C and 54+/-5% RH respectively).
      RESULTS: Total emitted mass (5 measurements/device) was significantly greater for
      HFA-BDP (14.1+/-1.1 microg/actuation) compared with CFC-BDP (2.4+/-0.8
      microg/actuation) (paired t test, p < 0.001). More HFA-BDP (2.7 +/- 0.2
      microg/actuation) was lost from the delivery system during exhalation (0.9 +/-
      0.4 microg/actuation for CFC-BDP) (p < 0.001). The mass median aerodynamic
      diameter (MMAD) increased from 1.2 microm (room ambient) to 2.8 microm (higher
      temperature and humidity conditions) for HFA-BDP. In contrast, MMAD for CFC-BDP
      remained close to 4.6 microm under either condition, but particles finer than
      about 4.0 microm increased in size when the circuit was saturated. CONCLUSIONS:
      Total emitted mass for HFA-BDP was increased by a factor of 5.8 compared with CFC
      BDP, due largely to the finer particle size distribution of the HFA-based
      solution formulation. Additional water vapor required to operate the breathing
      circuit at close to body conditions resulted in fine particle growth with both
      formulations.

PMID- 14585115
TI  - The effect of arterial blood gas values on extubation decisions.
AB  - BACKGROUND: No studies have examined the clinical utility of arterial blood gas
      (ABG) values during spontaneous breathing trials (SBTs) for making extubation
      decisions. Nonetheless many intensive care units measure ABGs during an SBT to
      determine, in conjunction with other data, whether the SBT was successful.
      OBJECTIVE: Determine how often ABG values change extubation decisions. METHODS:
      Each patient was assessed at the bedside by one of 3 critical care attending
      physicians. Each assessment was made at the end of the SBT in which ABGs were
      obtained with the expectation of extubation. When a nurse, respiratory therapist,
      or resident was available, he or she also simultaneously and independently
      evaluated the patient and then reassessed with the ABG values. Physiologic data
      were recorded before and during the SBT, as the attending physician performed the
      bedside assessment. RESULTS: Eighty-three patients were studied during 100 SBTs.
      Heart rate, respiratory rate, and mean blood pressure increased. Blood oxygen
      saturation (measured via pulse oximetry [F(IO)(2)]) and the P(aO)(2)/F(IO)(2)
      ratio decreased significantly during SBTs. Concordant clinical and ABG assessment
      (to attempt a trial of extubation) led to extubation in 86 patients, 76 of whom
      remained extubated after 72 hours. Following 14 of the SBTs, the patients were
      not extubated. Seven of these were judged by the attending physicians to fail
      both clinically and following review of ABG values. Seven were judged successful
      clinically, but the patients were not extubated because the attending physician
      thought the ABG values were unfavorable. Bedside nurses, who assessed 72 SBTs,
      had 1 case in which the ABG values changed their extubation opinion. Resident
      trainees assessed 76 cases and had 5 changes of opinion based on ABG values.
      Respiratory therapists assessed 77 patients and had 4 such cases. The average
      changes in heart rate and blood pressure of patients not extubated were double
      those of extubated patients, but there were no significant differences in
      respiratory rate or P(aO)(2)/F(IO)(2) ratio between those groups. Ten patients
      (11.6%) were extubated based on the attending physician's decision but required
      re-intubation within 72 hours. CONCLUSION: These data suggest that ABG values did
      not change extubation decisions in 93% of cases. However, in 7 cases the ABG
      values changed the extubation decision. If even a few of those cases would have
      failed extubation without knowledge of the ABG values, the increased patient risk
      and cost associated with failed extubation would more than offset the relatively
      small cost of collecting ABG values from all patients who undergo SBT.

PMID- 14585117
TI  - Genetic control of lifespan: studies from animal models.
AB  - The premise that there are genes that wield a strong influence on longevity has,
      until recently, not been a popular one and there has been no concerted effort to
      find such genes. However, the finding that single genes can have large effects on
      the lifespans of yeast, worms and flies raises the possibility that individual
      genes in mammals may similarly have relatively large effects on longevity. Recent
      advances in mammalian genetics, many associated with the large-scale efforts to
      sequence the human and mouse genomes, have accelerated the search for longevity
      genes, principally in mice. Here, we review results using animal models that have
      recently shed light on genes regulating longevity and ageing patterns. A large
      number of genetically defined strains of mice are available and this, together
      with their established history of use in genetic research and their relatively
      short lifespans, has made murine models particularly useful. We also review our
      own work in which genes regulating mouse lifespan and those regulating cell
      cycling of haematopoietic progenitor cells have been mapped to the same locations
      in the genome. These results suggest that some of the same genes affect both
      traits, and further suggest a cause-and-effect relationship between cumulative
      cell-cycle activity and longevity of an organism.

PMID- 14585118
TI  - Molecular genetics of human epilepsies.
AB  - The term epilepsy encompasses a heterogeneous group of disorders, with a lifetime
      cumulative incidence of 3%. Genetic factors are thought to contribute to the
      aetiology in up to 60% of cases. Various molecular and cellular mechanisms give
      rise to epilepsy, and epilepsy genes fall into several distinct categories. They
      include genes in which mutations cause abnormal ion-channel function, disordered
      brain development, progressive neurodegeneration and disturbances of cerebral
      energy metabolism. In this review, we have focused on current understanding of
      the molecular genetic bases of human inherited epilepsies. Particular reference
      has been given to specific idiopathic epilepsies, neuronal migration disorders
      (cortical dysgeneses) and the progressive myoclonic epilepsies, and how
      information about this group of disorders might be used to develop new treatment
      strategies.

PMID- 14585119
TI  - HLA-B27 and disease pathogenesis: new structural and functional insights.
AB  - The human leukocyte antigen class I allele HLA-B27 is a major histocompatibility
      complex (MHC) antigen that is strongly associated with the spondyloarthritic
      group of human rheumatic diseases, the most common of which is ankylosing
      spondylitis. Although the mechanism underlying this disease association remains
      unknown, numerous theories have been proposed. Much more is known of the natural
      role of HLA-B27 in binding and presenting antigenic peptides to T cells. The
      'arthritogenic peptide hypothesis' suggests that the role of HLA-B27 in disease
      relates to its specificity for binding certain peptides. Recently, it has also
      been shown that HLA-B27 has an unusual cell biology and can adopt a novel
      homodimeric structure. In this review, a molecular model of the HLA-B27 homodimer
      is presented and the possible pathogenic significance of such a structure is
      discussed.

PMID- 14585120
TI  - Clinical relevance of the molecular mechanisms of resistance to anti-cancer
      drugs.
AB  - Resistance to anti-cancer drugs (drug resistance) can be defined in the
      laboratory by the amount of anti-cancer drug that is required to produce a given
      level of cell death (drug response). Clinical drug resistance can be defined
      either as a lack of reduction of the size of a tumour following chemotherapy or
      as the occurrence of clinical relapse after an initial 'positive' response to
      anti-tumour treatment. Many studies of tumour samples do not directly measure
      drug resistance in the laboratory (because it is difficult to perform functional
      assays on tumour tissue); instead, key proteins or genes that are involved in
      particular mechanisms of drug resistance have been proposed as 'markers' of drug
      resistance. In this review, we have focused on the problems that can arise when
      attempts are made to relate the relevance of laboratory-identified molecular
      mechanisms of drug resistance to anti-cancer drug resistance that occurs in
      patients.

PMID- 14585121
TI  - Genetic studies of osteoporosis.
AB  - Osteoporosis is a common condition of men and women, which is characterised by an
      increase in bone fragility due to a reduction in the amount of bone tissue.
      Predisposition to osteoporosis is largely genetically determined, and it is
      likely that several genes, each having a small effect, are involved. Bone density
      is determined by the peak bone mass achieved, and the rate and timing of
      subsequent bone loss. Twin and family studies suggest that the genetic
      determinants of bone density in later life influence predominantly, but not
      exclusively, peak bone mass. Although many genes influence bone density in both
      males and females, at different skeletal sites and in different age groups, it is
      likely that the magnitude of individual genetic effects differs in different
      population subsets and in different environmental settings. Thus, weak to
      moderate genetic effects might be identified only in specific subsets of the
      population. Rapid advances in the field of human genetics during the past decade
      have greatly improved our chances of successfully identifying genes that are
      involved in complex genetic conditions such as osteoporosis, and ultimately might
      lead to the development of new diagnostic and predictive tests as well as novel
      treatments for this condition. In this review, we have outlined the methods that
      are currently being employed to identify osteoporosis genes and also the progress
      that has been made to date in this field.

PMID- 14585122
TI  - Poliovirus vaccination: current understanding of poliovirus interactions in
      humans and implications for the eradication of poliomyelitis.
AB  - Poliomyelitis is a paralytic disease of the motor neurones of the central nervous
      system, which is caused by poliovirus. The virus is transmitted by the faecal
      oral route, and if virus replication is confined to the gut, it is harmless.
      Poliomyelitis is an ancient human disease, but was rare until the beginning of
      the 20th century, when children began to be exposed to the virus at older ages
      and were, therefore, no longer protected by maternal antibody, which had already
      been lost. Inactivated polio vaccines are increasingly being used in those
      countries in which poliomyelitis has been brought under control; however, live
      vaccines are still the most widely used types and the World Health Organization
      (WHO) have set the goal of using such vaccines to eliminate the wild-type virus
      throughout the world by the year 2000. Substantial progress has been made to this
      end; however, the strains of poliovirus that are used as vaccines are able to
      adapt rapidly to the human gut, losing their attenuated (weakened) character
      within a few weeks. Currently, there is urgent debate about the best method of
      stopping vaccination against poliomyelitis once the wild-type poliovirus has been
      eliminated completely, so that the vaccine-strain virus will also be eliminated.
      Proposed strategies include the abrupt cessation of vaccination with the live
      virus worldwide, followed by the optional use of inactivated vaccines for an
      appropriate period. Further information about both the epidemiology and the
      pathogenesis of the disease is required before an informed choice can be made.
      The topics covered in this article include a brief history of studies of the
      disease, its pathogenesis and its control by vaccination, the molecular biology
      of the live vaccines, which have been extremely successful in controlling
      poliomyelitis so far, and the concerns that are raised as the eradication of the
      wild-type virus approaches.

PMID- 14585123
TI  - Gene therapy: potential applications in clinical transplantation.
AB  - Gene therapy continues to offer much hope for the future treatment of a variety
      of clinical conditions. The development of tailored, novel gene transfer vectors
      will improve the efficiency and stability of therapeutic gene expression in the
      many settings of gene therapy. In the context of tissue and organ
      transplantation, gene therapy is being harnessed to prevent the acute and chronic
      rejection of transplanted tissues by introducing either new genes that are
      important in preventing rejection (e.g. co-stimulatory blocking molecules or
      immunosuppressive cytokines) or antisense nucleic acids to block the production
      of rejection-associated molecules such as adhesion molecules. The delivery of
      genes by gene therapy vectors that encode foreign donor antigens (alloantigens)
      might also be an effective means of inducing donor-specific unresponsiveness
      (immunological tolerance) in the recipient, perhaps eliminating the requirement
      for potentially harmful whole-body immunosuppression.

PMID- 14585124
TI  - Molecular genetics and the assessment of human cancers.
AB  - The past 20 years have seen rapid advances in the understanding of the biology of
      human cancers, and a large body of evidence now supports the idea that
      accumulated genetic changes underlie the development of neoplasia. In this
      article, we have reviewed the current research into the genetic bases of cancer
      and discussed the potential clinical applications of recent advances, with
      particular reference to the possibility of using molecular genetic tests for pre
      symptomatic screening, clinical diagnosis and clinical staging. The possibility
      that the genetic profile of a tumour, its 'molecular fingerprint', will improve
      the ability of oncologists to predict tumour behaviour and thus help to determine
      optimum treatment has also been considered. Although the potential for the
      application of molecular genetic technologies is enormous, these technologies
      have yet to be subjected to rigorous evaluation in a clinical setting, and much
      work needs to be done before they are adopted for use in routine clinical care.

PMID- 14585125
TI  - Structure-function analysis and the molecular origins of anti-DNA antibodies in
      systemic lupus erythematosus.
AB  - Patients with the autoimmune rheumatic disease systemic lupus erythematosus (SLE
      or 'lupus') develop a wide variety of clinical and serological manifestations
      including the presence of antibodies to double-stranded DNA (dsDNA), which are
      often diagnostic and potentially pathogenic. In this review, we have examined the
      links between the structure and function of anti-dsDNA antibodies, emphasising
      their clinical associations. We have also reviewed studies involving animal
      models, the analysis of human antibody sequences and studies of, and using,
      computer modelling and crystal structure.

PMID- 14585126
TI  - Cell motility and cell morphology: how some viruses take control.
AB  - Viruses replicate inside host cells, where they use host biochemical and
      structural components to facilitate the production of new virus particles. As a
      consequence of co-evolution with their hosts, viruses have acquired host genes
      and genetic mutations that confer dominance over normal cell function. Research
      on virus-cell interactions has focused on the identification of mechanisms of
      virus dominance in order to develop therapeutic strategies for preventing
      productive infection. Although such research remains an essential part of
      molecular virology, viruses are also important genetic tools that can be used to
      analyse cell function. Because virus genomes contain genetic information, some of
      which was derived from host cells, it is possible that the analyses of virus-host
      interactions might lead to the identification of functionally dominant virus
      genes and novel eukaryotic counterparts. In this article, we have described how
      transforming and non-transforming viruses can control cell motility (cell
      migration or membrane projection), and explained how the analysis of virus
      cytopathic effects (CPEs) led to the identification of a novel family of cellular
      genes that regulate diverse aspects of cell motility.

PMID- 14585127
TI  - Human herpesvirus 7.
AB  - Human herpesvirus 7 (HHV-7) is a recently described T-lymphotropic herpesvirus,
      which infects almost all children by the age of three years and persists
      lifelong, with the shedding of infectious virus in saliva. HHV-7 is similar to
      human herpesvirus 6 (HHV-6) in its genetic content and in many of its biological
      properties, which include the ability to cause at least some cases of exanthem
      subitum (roseola). Despite these similarities, important differences between HHV
      7 and HHV-6 exist, including the fact that HHV-7 binds to the cellular CD4
      molecule and uses this protein as a necessary component of its receptor, while
      HHV-6 binds to a different (and unknown) receptor. Furthermore, the pathogenesis
      and sequelae of HHV-7 infection remain very poorly understood. This review
      provides a critical summary of research on HHV-7.

PMID- 14585128
TI  - Human herpesvirus 6.
AB  - Human herpesvirus 6 (HHV-6) is a T-lymphotropic herpesvirus, which infects almost
      all children by the age of two years and persists lifelong. Two distinct variants
      of HHV-6, HHV-6A and HHV-6B, have been described, and the latter has been shown
      to be a common cause of acute febrile illnesses in young children, including
      exanthem subitum (roseola). HHV-6 has also been associated with a number of
      neurological disorders, including encephalitis and seizures, and the virus has
      been postulated to play a role in acquired immunodeficiency syndrome (AIDS),
      multiple sclerosis (MS) and chronic fatigue immunodeficiency syndrome (CFIDS).
      This review provides a critical summary of research conducted on HHV-6.

PMID- 14585129
TI  - Clinical disease, immunity and protection against Plasmodium falciparum malaria
      in populations living in endemic areas.
AB  - Malaria remains one of the biggest health problems in large parts of the world.
      In sub-Saharan Africa alone, it is currently estimated that there are more than
      150 million clinical cases annually, and that about 2 million people die from the
      disease every year. The bulk of malaria-related morbidity and mortality in an
      endemic setting (malaria is regularly found) is concentrated in children below
      the age of five years, and the increasing resistance to infection and disease
      with age is conventionally thought to reflect a slow and gradual acquisition of
      protective immunity. Many recent and comprehensive reviews of malarial immunity
      exist; rather than attempting to add another, this review summarises some of the
      recent evidence on how protective immunity is acquired in humans and what
      precipitates clinical disease, specifically as it relates to populations living
      in areas where the disease is endemic. It is becoming increasingly clear that
      naturally acquired protective immunity depends largely on responses directed
      against highly variable parasite antigens. This implies that a successful blood
      stage vaccine against this disease must be able to either induce protective
      responses against many of these variants, or artificially initiate protective
      immune responses that do not normally occur following natural exposure to the
      parasites. Such protective immune responses might either rely on a different
      immunological mechanism, or be directed against other antigens, other than those
      seen in naturally acquired protective immunity. It remains to be seen whether it
      will be possible to induce protective responses such as these by 'artificially'
      immunising humans.

PMID- 14585130
TI  - Human cellular immune responses against human papillomaviruses in cervical
      neoplasia.
AB  - Human papillomaviruses (HPVs) are ubiquitous DNA viruses that infect cutaneous
      and mucosal epithelia. A subset of HPVs infects the female genital tract, to
      induce cervical lesions that can progress to malignancy in some women. DNA from
      HPVs can be found in >94% of cervical carcinomas (CaCx) worldwide; this strong
      association suggests that it might be possible to develop either prophylaxis or
      therapies for cervical neoplasia, based on the manipulation of human immune
      responses against HPVs. This review examines the current research into human
      immune responses against HPVs in CaCx and the potential impact of this research
      on human health.

PMID- 14585131
TI  - The malaria genome sequencing project.
AB  - An international consortium of genome centres, advanced development teams and
      funding agencies has begun the task of sequencing the genome of the parasite
      Plasmodium falciparum, the most important cause of human malaria. Sequencing is
      proceeding chromosome by chromosome, and the annotated sequence of chromosome 2
      is nearly finished. With the continual release of sequence data as they are
      generated, malaria researchers have access to a steady stream of genomic
      sequences and will soon have the complete annotation of all of the estimated 5000
      7000 P. falciparum genes. The task will then be how to best apply these data to
      the development of new anti-malarial drugs, vaccines and diagnostic tests. This
      review provides a brief overview of the Malaria Genome Sequencing Project and
      suggests potential directions for future malaria research.

PMID- 14585132
TI  - Measuring human T-lymphocyte function.
AB  - lymphocytes (T cells) play critical roles in the regulation of immune responses,
      and are responsible for mediating many of the effector mechanisms of the immune
      system. For this reason, there has always been a need for assays to measure
      accurately the activity of populations of T cells, both in model (animal) systems
      and in humans. The expansion of the biotechnology industry has led to a dramatic
      increase in the number of novel immunotherapeutics that are being developed for
      the treatment of cancer, autoimmune disorders and infectious diseases. This
      increase in activity in the field of immunotherapy, coupled with the expense of
      clinical trials, has led to renewed interest in methods that accurately assess T
      cell function, as researchers seek to maximise the amount of information that can
      be obtained from each clinical study. Assessing the quantitative and qualitative
      nature of a T-cell response, for example following vaccination or
      immunosuppressive therapy, can provide valuable information about the efficacy of
      a treatment, in place of a clinical endpoint. This article reviews some of the
      established methods that are used to monitor human T-cell activity, and describes
      some new approaches that are in development to increase the speed, sensitivity
      and relevance of such methods.

PMID- 14585133
TI  - Searching the unknown with gene trapping.
AB  - dramatic increase in sequence information, both in the form of complementary DNA
      (cDNA) and genomic DNA, has created a huge gap between the discovery of genes and
      the process of identifying gene function. To fill this gap, the 'gene-trapping'
      approach has been developed; this combines into a single process the three stages
      of gene cloning, the study of the pattern of gene expression and the analysis of
      the respective mutant phenotype. Recent results indicate that gene trapping can
      be used successfully to clone specific genes that are involved in the development
      of the central nervous system, limbs and haematopoietic system. Continuous
      improvements in the design of trapping vectors, faster sequencing of cDNA clones
      and more-efficient in vitro pre-screening will certainly aid the large-scale
      trapping of mammalian genomes.

PMID- 14585135
TI  - The role of cytokines in immunological tolerance: potential for therapy.
AB  - Current immunosuppression protocols, although often effective, are nonspecific
      and therefore hazardous. Consequently, immunological tolerance that is antigen
      specific and does not globally depress the patient's immune system has become one
      of the Holy Grails of immunology. Since the discovery that cytokines have
      immunomodulatory effects, extensive research has investigated the potential of
      these molecules to induce and maintain specific immunological tolerance in the
      context of transplantation, allergy and autoimmunity. In this article, we review
      the possible mechanisms by which cytokines can modulate the immune response and
      the animal models that frequently confound the theory that a single cytokine, or
      group of cytokines, can induce tolerance in a predictable manner. Finally, we
      discuss the role of cytokines at a paracrine level, particularly in the context
      of inducing and maintaining antigen-specific, regulatory T cells with the
      clinical potential to suppress specific immune responses.

PMID- 14585134
TI  - Substrate deprivation: a new therapeutic approach for the glycosphingolipid
      lysosomal storage diseases.
AB  - The glycosphingolipid (GSL) lysosomal storage diseases are a family of human
      metabolic diseases that, in their severest forms, cause death in early infancy,
      as a result of progressive neurodegeneration. They are caused by mutations in the
      genes encoding the glycohydrolases or the activator proteins that catabolise GSLs
      within lysosomes. In these diseases the GSL substrate of the defective enzyme
      accumulates in the lysosome, where it is stored and leads to cellular dysfunction
      and disease. The therapeutic options for treating these diseases are relatively
      limited; in fact, there are currently no available therapies for most of these
      disorders. The problem is further compounded by difficulties in delivering
      therapeutic agents to the central nervous system, which is where the pathology is
      frequently manifested. To date, research effort has mainly focused on strategies
      for augmenting enzyme concentrations to compensate for the underlying defect.
      These strategies include bone-marrow transplantation, enzyme-replacement therapy
      and gene therapy. Our group has been exploring the alternative strategy of
      substrate deprivation. This approach aims to balance the rate of GSL synthesis
      with the impaired rate of GSL breakdown. Studies using an asymptomatic mouse
      model of Tay-Sachs disease have shown that substrate deprivation prevents GSL
      storage. In a severe neurodegenerative mouse model of Sandhoff disease, substrate
      deprivation delayed the onset of symptoms and disease progression, and
      significantly increased life expectancy. The implications of this research for
      human therapy have been discussed.

PMID- 14585136
TI  - Chaperonins are cell-signalling proteins: the unfolding biology of molecular
      chaperones.
AB  - The chaperonins are a subgroup of oligomeric molecular chaperones; the best
      studied examples are chaperonin 60 (GroEL) and chaperonin 10 (GroES), both from
      the bacterium Escherichia coli. At the end of the 20th century, the paradigm of
      chaperonins as protein folders had emerged, but it is likely that during the 21st
      century these proteins will come to be viewed as intercellular signals. Indeed,
      it is possible that the chaperonins were among the first intercellular signalling
      proteins to evolve. During the past few years, it has emerged that chaperonin 10
      and chaperonin 60 can be found on the surface of various prokaryotic and
      eukaryotic cells, and can even be released from cells. Secreted chaperonins can
      interact with a variety of cell types, including leukocytes, vascular endothelial
      cells and epithelial cells, and activate key cellular activities such as the
      synthesis of cytokines and adhesion proteins. Much has been made of the high
      degree of sequence conservation among the chaperonins, particularly in terms of
      the immunogenicity of these proteins. However, different chaperonin 60 proteins
      can bind to different cell-surface receptors, including the Toll-like receptors,
      suggesting that this family of proteins cannot be treated as one biological
      entity and that several subfamilies may exist. Chaperonins have been implicated
      in human diseases on the basis of their immunogenicity. The finding that
      chaperonins can also induce tissue pathology suggests that they may play roles in
      infections and in idiopathic diseases such as atherosclerosis and arthritis.

PMID- 14585137
TI  - Molecular targets for existing and novel immunosuppressive drugs.
AB  - Anti-neoplastic cytostatic antiproliferative agents, such as methotrexate, 6
      mercaptopurine and cyclophosphamide, were originally used as immunosuppressive
      drugs. Although these agents induced only modest anti-rejection activity, they
      caused serious non-specific bone marrow suppression, impairing host resistance
      and increasing the incidence of infections. Unlike these non-selective agents,
      cyclosporine A, tacrolimus and sirolimus act more selectively on different stages
      of the T-lymphocyte (T-cell) and B-lymphocyte (B-cell) activation cycles;
      however, cyclosporine and tacrolimus are nephrotoxic, whereas sirolimus causes
      hypertriglyceridaemia. Thus, despite this progress, continued efforts must be
      made to develop and test new, potentially very selective agents. The agent 15
      deoxyspergualin moderately inhibits both mitogen-stimulated T-cell proliferation
      and the generation of cytotoxic T lymphocytes (CTLs) but does not affect the
      production of interleukin 2 (IL-2). Another drug, FTY720, has a unique action to
      prevent rejection, by altering the homing of lymphocytes to the lymphoid
      compartments. The newest members of the family of antiproliferative agents,
      namely mycophenolate mofetil, leflunomide and brequinar, are potentially more
      selective than their predecessors. However, the most promising agents are
      produced using antisense technology. This approach involves the design of
      antisense oligodeoxynucleotides; these novel drugs are designed to block
      allograft rejection by blocking selected messenger RNA (mRNA). This review
      outlines the mechanisms of action, the limitations of application and the
      molecular or cellular targets of traditional agents, newly developed drugs and
      also antisense technology, which is an example of a new application of molecular
      medicine.

PMID- 14585138
TI  - Novel molecular cytogenetic techniques for identifying complex chromosomal
      rearrangements: technology and applications in molecular medicine.
AB  - Molecular cytogenetic techniques that are based on fluorescence in situ
      hybridisation (FISH) have become invaluable tools for the diagnosis and
      identification of the numerous chromosomal aberrations that are associated with
      neoplastic disease, including both haematological malignancies and solid tumours.
      FISH can be used to identify chromosomal rearrangements, by detecting specific
      DNA sequences with fluorescently labelled DNA probes. The technique of
      comparative genomic hybridisation (CGH) involves two-colour FISH. It can be used
      to establish ratios of fluorescence intensity values between tumour DNA and
      control DNA along normal reference metaphase chromosomes, and thereby to detect
      DNA copy-number changes such as gains and losses of specific chromosomal regions
      and gene amplifications. Spectral karyotyping (SKY) is a novel molecular
      cytogenetic method for characterising numerical and structural chromosomal
      aberrations. SKY involves the simultaneous hybridisation of 24 differentially
      labelled chromosome-painting probes, followed by spectral imaging and chromosome
      classification, and produces a colour karyotype of the entire genome. The use of
      SKY has contributed significantly to the identification of chromosomal anomalies
      that are associated with constitutional and cancer cytogenetics, and has revealed
      many aberrations that go undetected by traditional banding techniques. In this
      article, we have reviewed these new molecular cytogenetic techniques and
      described their various applications in molecular medicine.

PMID- 14585139
TI  - Islet cell transplantation for insulin-dependant diabetes mellitus: perspectives
      from the present and prospects for the future.
AB  - The long-term complications of insulin-dependant diabetes mellitus have become a
      major health care problem, and it is now clear that they arise from inadequate
      homeostatic control of blood glucose by injected replacement insulin.
      Transplantation of pancreatic islets is arguably the most logical approach to
      restoring metabolic homeostasis in people with diabetes. This review looks at the
      current status of human islet transplantation and the problems that remain. These
      include: (1) the limited supply of human islet tissue available for
      transplantation; (2) the adverse effects of current immunosuppressive protocols
      on diabetic patients; (3) the problems of primary nonfunction of the transplanted
      islets; (4) the rejection of islets; and (5) the recurrence of autoimmune
      diabetic disease. Some of the approaches that might solve these problems are then
      examined: (1) immune modulation to reduce or prevent immune attack by the
      recipient's immune system; (2) immunoisolation to prevent recognition of the
      islet graft; (3) induction of tolerance; (4) xenotransplantation using islets
      derived from animals; and (5) gene therapy.

PMID- 14585140
TI  - Strategies for cancer therapy using carcinoembryonic antigen vaccines.
AB  - Advances in molecular biology and immunology have renewed interest in the
      development of vaccines for the treatment or prevention of cancer. Research over
      the past 10 years has focused on the identification of suitable tumour antigens
      to use as targets for a variety of vaccine strategies. Carcinoembryonic antigen
      (CEA) was one of the first tumour antigens described, and is commonly expressed
      by a wide range of adenocarcinomas. Recent studies have identified several human
      leukocyte-antigen-restricted epitopes (short peptides) within the CEA protein
      that can be recognised by human T lymphocytes (T cells). Although CEA-expressing
      tumour cells are generally weakly recognised by the immune system, several new
      strategies have been used to enhance immune responses against CEA. This includes
      using antibodies directed against CEA; inserting the CEA gene into recombinant
      viruses and bacteria as viral and bacterial vaccines; pulsing the CEA protein,
      peptides, DNA or RNA onto dendritic cells (specialised antigen-presenting cells);
      and combining CEA vaccines with cytokines or co-stimulatory molecules to increase
      vaccine effectiveness. Other factors that might be important in establishing
      systemic immunity against CEA are the dose, route, timing, and choice of vector
      and adjuvants for vaccine administration. Further research in understanding the
      fundamental processes involved in tumour-cell recognition by the immune system,
      better animal models, and improved clinical trial designs will help to define the
      full potential of CEA as a target for cancer vaccine development.

PMID- 14585141
TI  - New technologies in scanning probe microscopy for studying molecular interactions
      in cells.
AB  - Atomic force microscopy (AFM) is a specialised form of scanning probe microscopy,
      which was invented by Binnig and colleagues in 1986. Since then, AFM has been
      increasingly used to study biomedical problems. Because of its high resolution,
      AFM has been used to examine the topography or shape of surfaces, such as during
      the molecular imaging of proteins. This, combined with the ability to operate
      under known force regimes, makes AFM technology particularly useful for measuring
      intermolecular bond forces and assessing the mechanical properties of biological
      materials. Many of the constraints (e.g. complex instrumentation, slow
      acquisition speeds and poor vertical range) that previously limited the use of
      AFM in cell biology are now beginning to be resolved. Technological advances will
      enable AFM to challenge both confocal laser scanning microscopy and scanning
      electron microscopy as a method for carrying out three-dimensional imaging. Its
      use as both a precise micro-manipulator and a measurement tool will probably
      result in many novel and exciting applications in the future. In this article, we
      have reviewed some of the current biological applications of AFM, and illustrated
      these applications using studies of the cell biology of bone and integrin
      mediated adhesion.

PMID- 14585142
TI  - Molecular mechanisms of immunity in corneal allotransplantation and
      xenotransplantation.
AB  - Corneal allotransplantation is the most common and successful form of solid organ
      transplantation in humans. In uncomplicated cases, the two-year graft survival
      rate is over 90%. This extraordinary success can be attributed in part to various
      features of the normal cornea and anterior segment that together account for
      their 'immune-privileged' status. However, despite this success, a significant
      number of corneal grafts fail and immunological rejection remains by far the
      leading cause of graft failure. Studies on animal models of corneal
      transplantation have yielded a wealth of information on the molecular and
      cellular features of graft rejection, and have established that this process is
      mediated primarily by CD4+ T cells of the T helper 1 (Th1) phenotype. In
      addition, studies have elucidated that certain facets of allosensitisation differ
      between corneal and other solid organ transplants. On the basis of these
      findings, novel experimental strategies selectively targeting the afferent or
      efferent arms of corneal alloimmunity have provided promising results in
      preventing corneal allograft rejection in the laboratory. Finally, because of the
      global shortage of human donor corneas, there is currently renewed interest in
      the possibility of using corneas from other species for transplantation into
      human eyes (xenotransplantation). Preliminary studies on animal models of corneal
      xenotransplantation have documented both antibody-mediated and cell-mediated
      responses that might play important roles in the accelerated rejection observed
      in corneal xenotransplants. This review synthesises the principal concepts
      emerging from studies of the molecular mechanisms in corneal transplant
      immunology.

PMID- 14585143
TI  - Chemokines in cancer.
AB  - Chemokines are small, chemotactic cytokines that direct migration of leukocytes,
      activate inflammatory responses and participate in many other pleiotropic
      functions, including regulation of tumour growth. Chemokines modulate tumour
      behaviour by three important mechanisms: regulation of tumour-associated
      angiogenesis, activation of a host tumour-specific immunological response, and
      direct stimulation of tumour cell proliferation in an autocrine fashion. All of
      these mechanisms are promising points of cancer intervention, and preclinical
      mouse models suggest that chemokine antagonists and agonists could become
      important in the development of new anticancer therapies.

PMID- 14585144
TI  - Immunological pathomechanisms in vitiligo.
AB  - Vitiligo is a depigmenting disorder characterised by the loss of melanocytes from
      the cutaneous epidermis. Although the exact aetiology of vitiligo has not yet
      been established, the abnormal immune responses frequently observed in vitiligo
      patients have led to the suggestion that, in some cases, the condition has an
      autoimmune component. Briefly, circulating autoantibodies and autoreactive T
      cells that recognise pigment cell antigens have been detected in the sera of a
      significant proportion of vitiligo patients compared with healthy individuals. In
      addition, vitiligo is often associated with other disorders that have an
      autoimmune origin, including Hashimoto's thyroiditis, Graves' disease, type 1
      insulin-dependent diabetes mellitus and Addison's disease. Furthermore, effective
      use of immunosuppressive therapies to treat vitiligo, the association of vitiligo
      with certain major histocompatibility complex antigens, and evidence from animal
      models of the disease have all added credence to the hypothesis that immune
      reactions play a role in vitiligo pathogenesis. This review presents and
      discusses the evidence for immunological pathomechanisms in vitiligo.

PMID- 14585145
TI  - Mechanisms of cell entry by influenza virus.
AB  - A wide range of viruses, including many human and animal pathogens representing
      various taxonomic groups, contain genomes that are enclosed in lipid envelopes.
      These envelopes are generally acquired in the final stages of assembly, as
      viruses bud from regions of the membrane of the infected cell at which virally
      encoded membrane proteins have accumulated. The viruses procure their membranes
      during this process and mature particles 'pinch off' from the cellular membranes.
      Under most circumstances, initiation of another round of infection is dependent
      on two critical functions supplied by the envelope proteins. The virus must bind
      to cell-surface receptors of a new host cell, and fusion of the viral and
      cellular membranes must occur to transfer the viral genome into the cell.
      Enveloped viruses have evolved a variety of mechanisms to execute these two basic
      functions. Owing to their relative simplicity, studies of binding and fusion
      using enveloped viruses and their components have contributed significantly to
      the overall understanding of receptor-ligand interactions and membrane fusion
      processes - fundamental activities involved in a plethora of biological
      functions.

PMID- 14585146
TI  - Molecular markers of metastasis in breast cancer: current understanding and
      prospects for novel diagnosis and prevention.
AB  - The early and clinically occult spread of viable tumour cells throughout the body
      is increasingly considered as a hallmark of cancer progression, because recent
      data suggest that these cells are precursors of subsequent distant relapse. Using
      monoclonal antibodies to epithelial cytokeratins or tumour-associated cell
      membrane glycoproteins, individual carcinoma cells can be detected in cytological
      bone marrow preparations at frequencies of 10(-5) to 10(-6). Prospective clinical
      studies have shown that the presence of these immunostained micrometastatic cells
      in bone marrow, as a frequent site of overt metastases, is prognostically
      relevant with regard to relapse-free period and overall survival. This screening
      approach might therefore be used to improve tumour staging and to guide
      stratification of patients for adjuvant therapy in clinical trials. Another
      promising clinical application is the use of these micrometastatic cells to
      monitor response to adjuvant therapies, which at present can be assessed only
      retrospectively after an extended period of clinical follow-up. This review
      summarises current data on the clinical significance of occult metastatic breast
      cancer cells in bone marrow.

PMID- 14585147
TI  - Heat shock proteins in health and disease: therapeutic targets or therapeutic
      agents?
AB  - For many years, heat shock or stress proteins have been regarded as intracellular
      molecules that have a range of housekeeping and cytoprotective functions, only
      being released into the extracellular environment in pathological situations such
      as necrotic cell death. However, evidence is now accumulating to indicate that,
      under certain circumstances, these proteins can be released from cells in the
      absence of cellular necrosis, and that extracellular heat shock proteins have a
      range of immunoregulatory activities. The capacity of heat shock proteins to
      induce pro-inflammatory responses, together with the phylogenetic similarity
      between prokaryotic and eukaryotic heat shock proteins, has led to the
      proposition that these proteins provide a link between infection and autoimmune
      disease. Indeed, both elevated levels of antibodies to heat shock proteins and an
      enhanced immune reactivity to heat shock proteins have been noted in a variety of
      pathogenic disease states. However, further evaluation of heat shock protein
      reactivity in autoimmune disease and after transplantation has shown that, rather
      than promoting disease, reactivity to self-heat shock proteins can downregulate
      the disease process. It might be that self-reactivity to heat shock proteins is a
      physiological response that regulates the development and progression of pro
      inflammatory immunity to these ubiquitously expressed molecules. The evolving
      evidence that heat shock proteins are present in the extracellular environment,
      that reactivity to heat shock proteins does not necessarily reflect adverse, pro
      inflammatory responses and that the promotion of reactivity to self-heat shock
      proteins can downregulate pathogenic processes all suggest a potential role for
      heat shock proteins as therapeutic agents, rather than as therapeutic targets.

PMID- 14585148
TI  - Interactions between laminin and epithelial cells in intestinal health and
      disease.
AB  - Laminins are a multigene family of extracellular matrix molecules.
      Quantitatively, they are one of the most abundant glycoproteins present in
      basement membranes. Functionally, they can modulate several key biological
      activities, including cell adhesion and migration, gene expression and cell
      survival. Variability in the spatial and temporal expression of laminins, as well
      as of their specific receptors of the integrin family, in various tissues and
      organs, suggests that different laminins perform distinct functions. This article
      focuses on the human intestinal epithelium as a paradigm to illustrate the
      potential relationship between laminin-cell interactions and the cell state. This
      rapidly renewing epithelium consists of spatially separated proliferative and
      differentiated cell populations located in the crypts and on the villi,
      respectively. Differential distributions of the various laminins and laminin
      binding integrins have been observed along the crypt-villus axis in both the
      developing and the adult intestine, and important alterations in the pattern of
      laminin expression have been reported in various intestinal pathologies, such as
      tufting enteropathy, Crohn's disease and ulcerative colitis, and colorectal
      cancer. More-direct approaches, including experimentation with in vitro and in
      vivo models, have provided evidence in support of a role for laminins in
      intestinal cell functions. Although further work is still needed, laminins emerge
      more and more as key regulators of specific cell functions important in both
      intestinal health and intestinal disease.

PMID- 14585149
TI  - New DNA-based PCR approaches for rapid real-time detection and prevention of
      group B streptococcal infections in newborns and pregnant women.
AB  - Group B streptococci (GBS) are an important cause of neonatal sepsis and
      meningitis, and maternal infection. Although the pathogenesis of GBS infection is
      not well understood, several virulence factors have been identified. Two
      prevention strategies have been proposed: chemoprophylaxis and immunoprophylaxis.
      Implementation of selective intrapartum chemoprophylaxis on the basis of either
      screening or risk assessment has led to a substantial decrease in the morbidity
      and mortality of GBS disease in both mothers and infants. Penicillin remains the
      antibiotic of choice with no reported resistant GBS so far, whereas resistance of
      10-20% of GBS to erythromycin and clindamycin has been reported in North America.
      Chemoprophylaxis based on screening requires optimal detection methods for GBS,
      which involve selective broth culture of combined vaginal and anal samples. Other
      conventional methods are useful for rapid identification of heavily colonised
      women, but are unreliable for the detection of light GBS colonisation because of
      poor sensitivity. GBS-specific polymerase chain reaction (PCR) assays using real
      time PCR coupled with fluorescence-labelling technology offer powerful tools for
      sensitive and specific, yet rapid (less than 1 h), detection of GBS directly from
      clinical specimens at the time of delivery. The application of these assays to
      the current prevention strategies will simplify the prevention practice and
      rationalise the use of antibiotics. Immunoprophylaxis relies on the development
      of new vaccines against GBS, and active research is being conducted in this area.

PMID- 14585150
TI  - Atherosclerosis: role of chemokines and macrophages.
AB  - Atherosclerosis is a pathological process that takes place in the major arteries
      and is the underlying cause of heart attacks, stroke and peripheral artery
      disease. The earliest detectable lesions, called fatty streaks, contain
      macrophage foam cells that are derived from recruited monocytes. More-advanced
      atherosclerotic lesions, called fibro-fatty plaques, are the result of continued
      monocyte recruitment and smooth muscle cell migration and proliferation. Variable
      numbers of CD4+ T cells are found in atherosclerotic lesions, and cytokines
      secreted by T helper 1 (Th1)- or Th2-type cells can have a profound influence on
      macrophage gene expression within atherosclerotic plaques. This review briefly
      addresses the key features of macrophage biology and discusses the factors that
      influence the growth and development of atherosclerotic lesions (atherogenesis).
      It then considers the potential role of chemokines in mediating monocyte
      recruitment and macrophage differentiation within atherosclerotic lesions.

PMID- 14585151
TI  - Unique molecular markers in human endometriosis: implications for diagnosis and
      therapy.
AB  - Endometriosis originates in the uterine lining and affects ~20% of reproductive
      age women. The disease often causes chronic pelvic pain, affects ovulatory
      function and influences fertility. Although laparoscopic diagnosis of uterine
      endometriosis is quite specific, direct visualisation can be difficult or
      inaccurate in some circumstances, and it is not useful for diagnosing extra
      abdominal disease. Laparoscopy is an invasive procedure, has significant
      morbidity and cannot be carried out frequently to monitor efficacy of therapy and
      the possibility of recurrence. Thus, a specific, non-invasive diagnostic test is
      required. One intriguing area of research uses the technology of
      radioimmunotargeting, which has previously been used for cancer detection. This
      technique could have potential for the specific detection and eventual treatment
      of endometriosis. A marker, eosinophil peroxidase (EPO), has been identified that
      is expressed in ~90% of endometriosis specimens, and is not expressed or only
      weakly expressed in normal endometrium. The US Food and Drug Administration has
      approved a monoclonal antibody to EPO for investigation as an immunoimaging agent
      in cancers that exhibit eosinophilia. EPO targeting using this antibody could be
      useful for detecting and/or treating endometriosis.

PMID- 14585152
TI  - Epstein-Barr virus infection: basis of malignancy and potential for therapy.
AB  - The Epstein-Barr virus (EBV) is a human herpesvirus that is usually carried
      lifelong as an asymptomatic infection. EBV is the causative agent of infectious
      mononucleosis and has been linked to the development of several malignant
      tumours, including B-cell neoplasms such as Burkitt's lymphoma and Hodgkin's
      disease, certain forms of T-cell lymphoma, and some epithelial tumours, such as
      undifferentiated nasopharyngeal carcinoma and a proportion of gastric cancers.
      All these tumours are characterised by the presence of multiple extrachromosomal
      copies of the circular viral genome in the tumour cells and the expression of EBV
      encoded latent genes, which appear to contribute to the malignant phenotype. An
      increasing understanding of the function of EBV latent genes and of the nature of
      the immune response to the virus is providing exciting new possibilities for the
      treatment of EBV-associated malignancies. For example, adoptive transfer of virus
      specific cytotoxic T lymphocytes has already been of value in the treatment of
      EBV-positive B-cell lymphomas arising in post-transplant patients, and this
      approach is currently being investigated in other EBV-associated tumours. In
      addition, gene therapy offers the opportunity to deliver agents that might
      directly interfere with the function of specific EBV genes. This review
      summarises the role of EBV in malignancy. In particular, it focuses on the latent
      proteins as a basis for understanding how EBV might contribute to the process of
      transformation. Strategies to target EBV in tumours, potentially providing
      alternative therapeutic approaches, are also discussed.

PMID- 14585153
TI  - Measles virus and immunomodulation: molecular bases and perspectives.
AB  - Measles virus (MV) remains among the most potent global pathogens, killing more
      than 1 million children annually. The virus induces a profound suppression of
      immune functions that favours the establishment of, and aggravates the course of,
      secondary infections. By contrast, MV-specific immune responses are efficiently
      generated, and these clear the virus from the organism and confer a long-lasting
      immunity. As sensitisers of pathogen encounter and instructors of the adaptive
      immune response, professional antigen-presenting cells (APCs) such as dendritic
      cells play a decisive role in the induction and quality of the MV-specific immune
      response. However, key features of immune suppression associated with MV are
      compatible with interference with APC maturation and function, and subsequent
      qualitative and quantitative alterations of T-cell activation.

PMID- 14585154
TI  - The molecular genetics of schizophrenia: an emerging consensus.
AB  - Schizophrenia is perhaps the most debilitating mental disease and determining the
      underlying cause has become a challenging area of psychiatric research. It is
      relatively well established that genes play a role in the aetiology of
      schizophrenia. In this article, a review of important findings related to
      schizophrenia as a genetic trait will be provided, including a discussion of
      family, twin and adoption studies. Molecular genetic studies of specific
      candidate genes are then reviewed. Some controversies within the literature are
      examined and possible directions for future research are discussed.

PMID- 14585155
TI  - Advances in the diagnosis and treatment of leprosy.
AB  - Leprosy is a chronic infectious disease caused by Mycobacterium leprae that
      mainly affects the skin and peripheral nerves. Over recent years, many important
      advances have been made in developing molecular diagnostics, in identifying
      highly effective drugs and designing multidrug regimens for treatment, and in
      unravelling the genomic structure and functions of the leprosy bacillus. Using
      the new information about specific sequences of M. leprae, several gene probes
      and gene amplification systems for confirming diagnosis and monitoring treatment
      have been developed. Among these, polymerase chain reaction (PCR)-based methods
      have been useful in confirming the diagnosis in paucibacillary leprosy (where few
      bacilli are present). RNA-targeting systems for monitoring the progress of
      treatment, in situ hybridisation techniques for analysing specimens with
      nonspecific histological features, and molecular methods for direct detection of
      rifampicin/dapsone resistance are other major technological advances with immense
      applied value. Several effective regimens for the treatment of leprosy have been
      developed, which include rifampicin, clofazimine and dapsone as core drugs.
      Although these regimens are generally satisfactory, limitations in terms of
      persisting activity and late reactions/relapses in paucibacillary leprosy, and
      persistence of dead and/or live organisms in multibacillary forms of the disease,
      have been observed.

PMID- 14585156
TI  - PAR-2: structure, function and relevance to human diseases of the gastric mucosa.
AB  - PAR-2 (protease-activated receptor 2), a G-protein-coupled receptor activated by
      certain serine proteases such as trypsin and tryptase, is now considered a
      physiologically important molecule and also a novel target for drug development.
      PAR-2 is widely distributed in the mammalian body, especially throughout the
      alimentary system. PAR-2 plays various roles in the alimentary, circulatory,
      respiratory and neuronal systems. In the gastric mucosa, PAR-2 modulates multiple
      functions and exerts mucosal cytoprotection mainly by activating sensory neurons.
      Thus, PAR-2 would appear to be a therapeutic target for treatment of gastric
      mucosal injury. Agonists and/or antagonists for PAR-2 might also be applicable to
      the clinical treatment of patients with inflammatory diseases in other organs.

PMID- 14585157
TI  - Muscular dystrophies, dilated cardiomyopathy, lipodystrophy and neuropathy: the
      nuclear connection.
AB  - An understanding of muscle structure and function is central to improving our
      knowledge of the group of muscle diseases referred to as muscular dystrophies.
      These diseases involve a progressive weakening and wasting of skeletal muscle,
      which can be associated with life-threatening cardiac arrhythmias. The vast
      majority of these diseases arise from defects in either cytoskeletal or
      structural proteins, resulting in a breakdown of muscle cell integrity. However,
      mutations in two nuclear proteins--emerin and lamin A/C--have also been
      demonstrated to give rise to a muscular dystrophy phenotype. In addition,
      mutations in lamin A/C can give rise to a dilated cardiomyopathy, a lipodystrophy
      or a neuropathy. It is far from clear how mutations in nuclear proteins can
      result in a dystrophy, or cause more than one clinically distinct disease.
      Understanding the functional role of nuclear proteins in causing these diseases
      will therefore provide novel insights into muscle function, and should hopefully
      provide new directions for treatment.

PMID- 14585158
TI  - Tissue engineering: TGF-beta superfamily members and delivery systems in bone
      regeneration.
AB  - The induction of bone formation requires three parameters that interact in a
      highly regulated process: soluble osteoinductive signals, capable responding
      cells, and a supporting matrix substratum or insoluble signal. The use of
      recombinant and naturally derived bone morphogenetic proteins and transforming
      growth factor beta(s) (TGF-beta(s)) has increased our understanding of the
      functions of these morphogens during the induction of endochondral bone
      formation. In addition, growing understanding of the cellular interactions of
      living tissues with synthetic biomaterials has led to the in vivo induction of
      bone formation using porous biomimetic matrices as an alternative to the use of
      autografts for bone regeneration. This review outlines the basis of bone tissue
      engineering by members of the TGF-beta superfamily, focusing on their delivery
      systems and the intrinsic induction of bone formation by specific biomimetic
      matrices with a defined geometry.

PMID- 14585159
TI  - Immunological hurdles in the path to gene therapy for Duchenne muscular
      dystrophy.
AB  - Patients with Duchenne muscular dystrophy (DMD), an X-linked lethal muscle
      wasting disease, have abnormal expression of the protein dystrophin within their
      muscle fibres. In the mdx mouse model of this condition, both germline and
      neonatal somatic gene transfers of dystrophin cDNAs have demonstrated the
      potential of gene therapy in treating DMD. However, in many DMD patients, there
      appears to be no dystrophin expression when muscle biopsies are immunostained or
      western blots are performed. This raises the possibility that the expression of
      dystrophin following gene transfer might trigger a destructive immune response
      against this 'neoantigen'. Immune responses can also be generated against the
      gene transfer vector used to transfect the dystrophic muscle, and the combined
      immune response could further damage the already inflamed muscle. These problems
      are now beginning to be investigated in immunocompetent mdx mice. Although much
      work remains to be done, there are promising indications that these immune
      responses might not prove as much of a concern as originally envisaged.

PMID- 14585160
TI  - Presenilin-interacting proteins.
AB  - Familial Alzheimer's disease (FAD) accounts for 5-10% of deaths from Alzheimer's
      disease (AD), and approximately 50% of these cases have been definitely linked to
      missense mutations in three genes, encoding the amyloid precursor protein (APP),
      presenilin 1 (PS1) and presenilin 2 (PS2). Of these, the vast majority of FAD
      linked mutations are within PS1. There has been an extensive effort to identify
      proteins that functionally interact with PS1 and PS2 because of their clear roles
      in FAD. The goal of this review is to describe these proteins and to discuss in
      more detail the probable biological functions of a subset of the better-studied
      interacting proteins. In particular, the review examines APP, Notch, nicastrin,
      modifier of cellular adhesion (MOCA), beta-catenin, and the group of proteins
      involved in cell death, calcium metabolism and cell adhesion. We argue that,
      although a few of the interacting proteins are unambiguously involved in well
      studied cellular pathways, their exact roles within these pathways have not been
      clearly defined, and indeed might vary between cell types. We also question the
      physiological relevance of some of the work linking PS to cell death pathways.
      Finally, we point out the value of using flies and worms to sort out the often
      contradictory work in the PS field, and we mention how knowledge of PS
      interacting pathways will contribute to the development of new therapeutic
      strategies in AD.

PMID- 14585161
TI  - Immune modulation by the cholera-like enterotoxins.
AB  - The role of cholera toxin and heat-labile enterotoxin in the pathogenesis of
      diarrhoeal disease has been well documented for many years. In addition to these
      deleterious effects, a wealth of data is accumulating that suggests that these
      toxins and their subunits might be used to modulate immune responses in a variety
      of beneficial ways. In this regard, the toxins can boost immune responses to
      unrelated antigens, leading to the possibility of their use in the generation of
      improved vaccines to a variety of pathogens. Furthermore, recent evidence
      suggests that recombinant preparations of the nontoxic B subunits of the toxins
      have distinct immunomodulatory activities, with potential applications to the
      treatment of autoimmune and inflammatory diseases. This article reviews our
      current understanding of the mechanisms of immune modulation by these fascinating
      proteins.

PMID- 14585162
TI  - Androgenetic alopecia: pathogenesis and potential for therapy.
AB  - Androgenetic alopecia occurs in men and women, and is characterised by the loss
      of hair from the scalp in a defined pattern. Determining factors appear to be
      genetic predisposition coupled with the presence of sufficient circulating
      androgens. The prevalence of this condition is high (up to 50% of white males are
      affected by 50 years of age) and, although there are no serious direct health
      consequences, the loss of scalp hair can be distressing. Knowledge of the
      pathogenesis of androgenetic alopecia has increased markedly in recent years. Pre
      programmed follicles on the scalp undergo a transformation from long growth
      (anagen) and short rest (telogen) cycles, to long rest and short growth cycles.
      This process is coupled with progressive miniaturisation of the follicle. These
      changes are androgen dependent, and require the inheritance of several genes. To
      date, only one of these genes, which encodes the androgen receptor (AR), has been
      identified. Of the many treatments available for androgenetic alopecia, only two
      (finasteride and minoxidil) have been scientifically shown to be useful in the
      treatment of hair loss. However, these therapies are variable in their
      effectiveness. Discovery of the involvement of the AR gene, and the
      identification of other genes contributing to the condition, might lead to the
      development of new and more effective therapies that target the condition at a
      more fundamental level.

PMID- 14585164
TI  - Gene therapy for cancer and metastatic disease.
AB  - Gene therapy has been applied to the treatment of cancer and metastatic disease
      for over ten years. Research in this area has utilised multiple gene therapy
      approaches including targeting tumour suppressor genes and oncogenes, stimulating
      the immune system, targeted chemotherapy, antiangiogenic strategies, and direct
      viral oncolysis. In recent years, gene delivery vectors have been developed that
      selectively target tumour cells through tumour-specific receptors, deletion of
      certain viral gene sequences, or incorporation of tumour-specific promoter
      sequences that drive gene expression. Preclinical models have produced promising
      results, demonstrating significant tumour regression and reduction of metastatic
      disease. Unfortunately, only limited responses have been observed in clinical
      trials. The main limitations in treating metastatic disease include poor vector
      transduction efficiencies and difficulties in targeting remote tumour cells with
      systemic vector delivery. Currently, various groups are investigating means to
      improve gene delivery and clinical responses by continuing to modify gene
      delivery vectors and by concentrating on combination gene therapy and
      multimodality therapy.

PMID- 14585163
TI  - Short-term and long-term cellular and molecular events following UV irradiation
      of skin: implications for molecular medicine.
AB  - Acute ultraviolet (UV) irradiation of normal human skin results in several
      clinical effects, including sunburn inflammation (erythema) and tanning,
      histological changes such as thickening of the epidermis, and local or systemic
      immunosuppression. Chronic UV irradiation leads to photoaging, sustained
      immunosuppression and photocarcinogenesis. Photocarcinogenesis involves the
      accumulation of genetic changes, as well as immune system modulation, and
      ultimately leads to the development of skin cancers. Recent advances in molecular
      and cellular biology have clarified the mechanisms of photocarcinogenesis,
      including the formation of DNA photoproducts, DNA repair, the mutation of proto
      oncogenes and tumour suppressor genes, and UV-induced immunosuppression. Further
      investigation and a better understanding of photocarcinogenesis are critical to
      the development of effective prevention and intervention strategies for human
      skin cancer.

PMID- 14585165
TI  - Toll-like receptors and intestinal defence: molecular basis and therapeutic
      implications.
AB  - Toll-like receptors (TLRs) play a principle role in distinct pathogen recognition
      and in the initiation of innate immune responses of the intestinal mucosa.
      Activated innate immunity interconnects downstream with adaptive immunity in
      complex feedback regulatory loops. Intestinal disease might result from
      inappropriate activation of the mucosal immune system driven by TLRs in response
      to normal luminal flora.

PMID- 14585166
TI  - Cobalamin transport proteins and their cell-surface receptors.
AB  - The primary function of cobalamin (Cbl; vitamin B12) is the formation of red
      blood cells and the maintenance of a healthy nervous system. Before cells can
      utilise dietary Cbl, the vitamin must undergo cellular transport using two
      distinct receptor-mediated events. First, dietary Cbl bound to gastric intrinsic
      factor (IF) is taken up from the apical pole of ileal epithelial cells via a 460
      kDa receptor, cubilin, and is transported across the cell bound to another Cbl
      binding protein, transcobalamin II (TC II). Second, plasma TC II-Cbl is taken up
      by cells that need Cbl via the TC II receptor (TC II-R), a 62 kDa protein that is
      expressed as a functional dimer in cellular plasma membranes. Human Cbl
      deficiency can develop as a result of acquired or inherited dysfunction in either
      of these two transmembrane transport events. This review focuses on the
      biochemical, cellular and molecular aspects of IF and TC II and their cell
      surface receptors.

PMID- 14585168
TI  - Genetic factors underlying prostate cancer.
AB  - Prostate cancer is one of the leading causes of cancer-related death in the USA.
      In the past decade, tremendous progress has been made in the identification and
      understanding of the genetic factors related to prostate cancer development.
      Unlike many other types of cancers, only a small fraction of prostate cancer
      cases are aggressive and life-threatening. The factors related to prostate cancer
      development and progression appear complex and diverse. This review summarises
      some of the important findings in the areas of genome and gene expression
      abnormalities in prostate cancer, and aims to provide a comprehensive view of new
      developments in these areas.

PMID- 14585167
TI  - Grb7-based molecular therapeutics in cancer.
AB  - Traditional anti-cancer drugs preferentially kill rapidly growing tumour cells
      rather than normal cells. However, most of these drugs have no preferential
      selection towards cancer cells and are taken up by the whole body, resulting in
      significant adverse side effects. Therapeutic molecules that could specifically
      inhibit undesirable phenotypes are an attractive way of eliminating cancer cells.
      There is a widespread effort to develop inhibitors against signal transduction
      molecules that play a key role in the proliferative, migratory and invasive
      properties of a cancer cell. Grb7 is an adaptor-type signalling protein that is
      recruited via its Src-homology 2 (SH2) domain to a variety of tyrosine kinases.
      Grb7 is overexpressed in breast, oesophageal and gastric cancers, and may
      contribute to the invasive potential of cancer cells. Molecular interactions
      involving Grb7 therefore provide attractive targets for therapeutic intervention.

PMID- 14585169
TI  - Innate immunity and brain inflammation: the key role of complement.
AB  - The complement inflammatory cascade is an essential component of the
      phylogenetically ancient innate immune response and is crucial to our natural
      ability to ward off infection. Complement is involved in host defence by
      triggering the generation of a membranolytic complex (the C5b-9 complex) at the
      surface of the pathogen. Complement fragments (opsonins; C1q, C3b and iC3b)
      interact with complement cell-surface receptors (C1qRp, CR1, CR3 and CR4) to
      promote phagocytosis and a local pro-inflammatory response that, ultimately,
      contributes to the protection and healing of the host. Complement is of special
      importance in the brain, where entrance of elements of the adaptive immune system
      is restricted by a blood-brain barrier. There is now compelling evidence that
      complement is produced locally in response to an infectious challenge. Moreover,
      complement biosynthesis and activation also occurs in neurodegenerative disorders
      such as Alzheimer's, Huntington's and Pick's diseases, and the
      cytolytic/cytotoxic activities of complement are thought to contribute to
      neuronal loss and brain tissue damage. However, recent data suggest that at least
      some of the complement components have the ability to contribute to
      neuroprotective pathways. The emerging paradigm is that complement is involved in
      the clearance of toxic cell debris (e.g. amyloid fibrils) and apoptotic cells, as
      well as in promoting tissue repair through the anti-inflammatory activities of
      C3a. Knowledge of the unique molecular and cellular innate immunological
      interactions that occur in the development and resolution of pathology in the
      brain should facilitate the design of effective therapeutic strategies.

PMID- 14585170
TI  - Metalloproteinases and their inhibitors in angiogenesis.
AB  - Angiogenesis, the formation of new blood vessels from the pre-existing
      vasculature, is an integral part of physiological processes such as embryonic
      development, the female reproductive cycle and wound healing. Angiogenesis is
      also central to a variety of pathologies including cancer, where it is recognised
      as being crucial for the growth of solid tumours. Matrix metalloproteinases
      (MMPs) are a family of soluble and membrane-anchored proteolytic enzymes that can
      degrade components of the extracellular matrix (ECM) as well as a growing number
      of modulators of cell function. Several of the MMPs, most notably MMP-2 and -9
      and membrane-type-1 MMP (MT1-MMP), have been linked to angiogenesis. Potential
      roles for these proteases during the angiogenic process include degradation of
      the basement membrane and perivascular ECM components, liberation of angiogenic
      factors, production of endogenous angiogenic inhibitors, and the unmasking of
      cryptic biologically relevant sites in ECM components. This review brings
      together what is currently known about the functions of the MMPs and the closely
      related adamalysin metalloproteinase (ADAM) family in angiogenesis, and discusses
      how this information might be useful in manipulation of the angiogenic process,
      with a view to controlling aberrant neovascularisation.

PMID- 14585171
TI  - Huntington's disease: molecular basis of neurodegeneration.
AB  - Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder
      caused by a CAG trinucleotide repeat expansion in the HD gene. The expanded
      repeats are translated into an abnormally long polyglutamine tract close to the N
      terminus of the HD gene product ('huntingtin'). Studies in humans and mouse
      models suggest that the mutation is associated with a deleterious gain-of
      function. Several studies have suggested that the large huntingtin protein is
      cleaved to produce a shorter N-terminal fragment containing the polyglutamine
      expansion, and that the polyglutamine expansion causes the protein fragment to
      misfold and form aggregates (inclusions) in the nuclei and processes of neurons.
      It is likely that neurotoxicity is caused by the misfolded protein in its soluble
      form, and/or in aggregates, and/or in the process of aggregation. A wide range of
      potential mechanisms for neurotoxicity have been proposed, including caspase
      activation, dysregulation of transcriptional pathways, increased production of
      reactive oxygen species, and inhibition of proteasome activity. In this review we
      consider the current status of research in the field and possible mechanisms
      whereby the HD mutation might result in neurodegeneration.

PMID- 14585172
TI  - Repeat expansion and autosomal dominant neurodegenerative disorders: consensus
      and controversy.
AB  - Repeat-expansion mutations cause 13 autosomal dominant neurodegenerative
      disorders falling into three groups. Huntington's disease (HD), dentatorubral
      pallidoluysian atrophy (DRPLA), spinal and bulbar muscular atrophy (SBMA), and
      spinocerebellar ataxias (SCAs) types 1, 2, 3, 7 and 17 are each caused by a CAG
      repeat expansion that encodes polyglutamine. Convergent lines of evidence
      demonstrate that neurodegeneration in these diseases is a consequence of the
      neurotoxic effects of abnormally long stretches of glutamines. How polyglutamine
      induces neurodegeneration, and why neurodegeneration occurs in only select
      neuronal populations, remains a matter of intense investigation. SCA6 is caused
      by a CAG repeat expansion in CACNA1A, a gene that encodes a subunit of the P/Q
      type calcium channel. The threshold length at which the repeat causes disease is
      much shorter than in the other polyglutamine diseases, and neurodegeneration may
      arise from expansion-induced change of function in the calcium channel.
      Huntington's disease-like 2 (HDL2) and SCAs 8, 10 and 12 are rare disorders in
      which the repeats (CAG, CTG or ATTCT) are not in protein-coding regions.
      Investigation into these diseases is still at an early stage, but it is now
      reasonable to hypothesise that the net effect of each expansion is to alter gene
      expression. The different pathogenic mechanisms in these three groups of diseases
      have important implications for the development of rational therapeutics.

PMID- 14585173
TI  - Nonviral gene delivery: techniques and implications for molecular medicine.
AB  - Medical research continues to illuminate the origins of many human diseases. Gene
      therapy has been widely proposed as a novel strategy by which this knowledge can
      be used to deliver new and improved therapies. Viral gene transfer is relatively
      efficient but there are concerns relating to the use of viral vectors in humans.
      Conversely, nonviral vectors appear safe but inefficient. Therefore, the
      development of an efficient nonviral vector remains a highly desirable goal. This
      review focuses on the numerous challenges preventing efficient nonviral gene
      transfer in vivo and discusses the many technologies that have been adopted to
      overcome these problems.

PMID- 14585174
TI  - Molecular mechanisms by which dietary isoflavones potentially prevent
      atherosclerosis.
AB  - Dietary isoflavones are currently receiving much attention because of their
      potential role in preventing coronary artery disease and other chronic diseases.
      Accumulating evidence from cell culture and laboratory animal experiments
      indicates that isoflavones have the potential to prevent or delay atherogenesis.
      Suggested mechanisms of action include: a reduction in low-density lipoprotein
      (LDL) cholesterol and a potential reduction in the susceptibility of the LDL
      particle to oxidation; (2) an improvement in vascular reactivity; (3) an
      inhibition of pro-inflammatory cytokines, cell adhesion proteins and nitric oxide
      (NO) production; and (4) an inhibition of platelet aggregation. These mechanisms
      are consistent with the epidemiological evidence that a high consumption of
      isoflavone-rich soy products is associated with a reduced incidence of coronary
      artery disease. Biological effects of isoflavones are dependent on many factors,
      including dose consumed, duration of use, protein-binding affinity, and an
      individual's metabolism or intrinsic oestrogenic state. Further clinical studies
      are necessary to determine the potential health effects of isoflavones in
      specific population groups as we currently know little about age-related
      differences in exposure to these compounds and there are few guidelines on
      optimal dose for cardiovascular health benefits.

PMID- 14585179
TI  - Kimchi and an active component, beta-sitosterol, reduce oncogenic H-Ras(v12)
      induced DNA synthesis.
AB  - The Korean fermented vegetable food, kimchi, has been demonstrated to have
      anticancer functional properties. This study examined the effect of kimchi
      samples, methanol extracts of commercially grown baechu cabbage kimchi (CK) and
      organically grown baechu cabbage kimchi (OK), as well as the dichloromethane
      fraction (DCM fr.) from CK, and the active compound (AC), which has been
      identified as largely beta-sitosterol, from DCM fr., on the Ras-dependent
      signaling pathway. CK, OK, and DCM fr. exhibited a greater inhibition against the
      proliferation of Rat2 fibroblasts transformed with Ras(v12) (HO6) than parental
      Rat2 fibroblasts. In addition, OK and DCM fr. showed a higher inhibitory effect
      than CK. Furthermore, we employed the single-cell microinjection technique,
      combined with 3-bromo-5'-deoxyuridine incorporation, to examine the effects of
      kimchi samples on DNA synthesis induced by microinjected oncogenic Ras(v12). When
      the DCM fr. and AC were used to treat Rat1 fibroblasts overexpressing human
      insulin receptors (HIRc-B) and microinjected with oncogenic H-Ras(v12), the DNA
      synthesis of injected cells was decreased, suggesting that kimchi might block the
      signaling pathway of oncogenic Ras(v12), thus preventing the proliferation of
      transformed cells. This study provides additional evidence that kimchi and its
      active components, including beta-sitosterol, have potential in both the
      prevention and treatment of cancer, and presents convincing evidence that the
      anticancer effects may be a result of an inhibition of Ras oncogene signaling.

PMID- 14585180
TI  - Chemopreventive effects of pomegranate seed oil on skin tumor development in CD1
      mice.
AB  - Pomegranate seed oil was investigated for possible skin cancer chemopreventive
      efficacy in mice. In the main experiment, two groups consisting each of 30, 4-5
      week-old, female CD(1) mice were used. Both groups had skin cancer initiated with
      an initial topical exposure of 7,12-dimethylbenzanthracene and with biweekly
      promotion using 12-O-tetradecanoylphorbol 13-acetate (TPA). The experimental
      group was pretreated with 5% pomegranate seed oil prior to each TPA application.
      Tumor incidence, the number of mice containing at least one tumor, was 100% and
      93%, and multiplicity, the average number of tumors per mouse, was 20.8 and 16.3
      per mouse after 20 weeks of promotion in the control and pomegranate seed oil
      treated groups, respectively (P <.05). In a second experiment, two groups each
      consisting of three CD(1) mice were used to assess the effect of pomegranate seed
      oil on TPA-stimulated ornithine decarboxylase (ODC) activity, an important event
      in skin cancer promotion. Each group received a single topical application of
      TPA, with the experimental group receiving a topical treatment 1 h prior with 5%
      pomegranate seed oil. The mice were killed 5 h later, and ODC activity was
      assessed by radiometric method. The experimental group showed a 17% reduction in
      ODC activity. Pomegranate seed oil (5%) significantly decreased (P <.05) tumor
      incidence, multiplicity, and TPA-induced ODC activity. Overall, the results
      highlight the potential of pomegranate seed oil as a safe and effective
      chemopreventive agent against skin cancer.

PMID- 14585181
TI  - Carnitine profiles during differentiation and effects of carnitine on
      differentiation of 3T3-L1 cells.
AB  - These experiments were conducted to investigate carnitine profiles during
      differentiation and the effects of carnitine on the differentiation of 3T3-L1
      cells. To induce cell differentiation, undifferentiated 3T3-L1 cells were treated
      with dexamethasone, 1-methyl-3-isobutylxanthine, and d-biotin. Carnitine was also
      exogenously added to the cells to test its effect on cell differentiation.
      Triglyceride, total lipid, total protein, nonesterified carnitine, acid-soluble
      acylcarnitine, and acid-insoluble acylcarnitine were analyzed during the
      differentiation of 3T3-L1 cells. Total lipid, triglyceride, and total protein
      increased during the 3T3-L1 cell differentiation. However, nonesterified
      carnitine, acid-soluble acylcarnitine, and acid-insoluble acylcarnitine
      concentrations were lower in the differentiated 3T3-L1 cells. In addition, the
      exogenously added carnitine inhibited the increases in triglyceride and total
      lipid levels. These results suggest that carnitine may have an inhibitory role on
      the early stage of 3T3-L1 cell differentiation.

PMID- 14585182
TI  - Dose-dependent protection by tomato against 7,12-dimethylbenz[a]anthracene
      induced genotoxicity and oxidative stress in mice.
AB  - This study was designed to investigate the protective role of pretreatment with
      graded doses of freshly prepared tomato paste against 7,12
      dimethylbenz[a]anthracene (DMBA)-induced genetic damage and oxidative stress in
      male Swiss mice. The incidence of bone marrow micronuclei and the extent of
      hepatic lipid peroxidation and the antioxidants glutathione, glutathione
      peroxidase, and glutathione S-transferase were monitored. Three different
      concentrations (0.5, 1, and 2 g/kg body weight) of tomato paste were tested for
      their anticlastogenic effects against DMBA (35 mg/kg body weight). Increased
      frequency of micronuclei and enhanced lipid peroxidation accompanied by
      compromised antioxidant defenses were observed in DMBA-treated animals.
      Pretreatment with all three doses of tomato paste significantly reduced the
      frequencies of DMBA-induced micronuclei and oxidative stress. These findings
      demonstrate that administration of tomato paste protects against the clastogenic
      effects of DMBA by decreasing lipid peroxidation and enhancing the antioxidant
      status.

PMID- 14585183
TI  - Anticarcinogenic properties of a daidzein-rich fraction isolated from soybean.
AB  - In a previous study, we demonstrated that the methanol extract of soybean powder
      contains an active component(s) that promotes the differentiation of HL-60 cells.
      Partial purification of the extract, using solvent fractionation and silica gel
      chromatography, produced an active fraction rich in daidzein. The daidzein-rich
      fraction (DRF) was evaluated for its cancer preventive potential by assessing its
      cytotoxic activity and effect on the expression of the transforming growth factor
      beta (TGF-beta) family of cytokines and their receptors. DRF appeared to exert
      cytotoxic activity via an apoptotic pathway as evaluated by a DNA fragmentation
      assay and caspase-3 induction. DRF also increased the expression of TGF-beta2,
      but had little effect on the expression of other members of the TGF-beta family
      of cytokines and their receptors, or on the expression of the vascular
      endothelial growth factor gene. In conclusion, the DRF isolated from the methanol
      extract of soybean may have the potential to prevent tumorigenesis and,
      therefore, deserves to undergo further evaluation of its active component(s) and
      in vivo evaluation for anticarcinogenic efficacy.

PMID- 14585185
TI  - trans-10, cis-12 conjugated linoleic acid reduces insulin-like growth factor-II
      secretion in HT-29 human colon cancer cells.
AB  - We previously demonstrated that a mixture of conjugated linoleic acid (CLA)
      isomers decreases colon cancer incidence in rats treated with 1,2
      dimethylhydrazine. Our in vitro studies have also shown that CLA inhibits the
      growth of HT-29 cells, a human colon cancer cell line. When we compared the
      individual potencies of the two main isomers found in the mixture of CLA isomers
      (e.g., cis-9, trans-11 [c9t11] and trans-10, cis-12 [t10c12]), t10c12 CLA
      decreased viable cell numbers in a dose-dependent manner. By contrast, c9t11 CLA
      had no effect. Therefore, the present study examined whether the decreased cell
      growth is related to changes in secretion of insulin-like growth factor (IGF)-II
      and/or IGF-binding proteins (IGFBPs) that have been shown to regulate HT-29 cell
      proliferation. Cells were incubated in serum-free medium with various
      concentrations of the individual CLA isomers, and immunoblot analysis of 24-hour,
      serum-free, conditioned media using a monoclonal anti-IGF-II antibody was
      performed. HT-29 cells secreted both mature 7,500 apparent molecular weight
      (M(r)) and higher-M(r) forms of IGF-II. t10c12 CLA decreased the levels of the
      higher-M(r) and the mature form of IGF-II in a dose-dependent manner, whereas
      c9t11 CLA had no effect. Ligand blot analysis of conditioned medium using (125)I
      IGF-II revealed that the production of IGFBP-2 and IGFBP-4 was also decreased by
      t10c12 CLA, whereas c9t11 CLA had no effect. Exogenous IGF-II abrogated the
      growth inhibition induced by t10c12 CLA. These results indicate that inhibition
      of HT-29 cell growth by t10c12 CLA may be mediated by decreasing IGF-II secretion
      in these cells.

PMID- 14585186
TI  - Toxic potential of dietary genistein isoflavone and beta-lapachone on
      capacitation and acrosome reaction of epididymal spermatozoa.
AB  - We determined if acrosomal reaction was influenced by exposure of sperm cells to
      two dietary phytochemicals, genistein isoflavone and beta-lapachone, using the
      rat model. Spermatozoa were capacitated in capacitating medium with or without
      genistein isoflavone and beta-lapachone, and the percentage of posttreatment
      acrosome reaction compared with controls was assessed with two fluorescent
      probes, chlortetracycline (CTC) and fluorescein isothiocyanate- Pisum sativum ag
      glutinin conjugate (FITC-PSA). Spermatozoa were permeabilized in ethanol and
      labeled with the FITC-PSA or CTC to determine the acrosome status. The results
      revealed that calcium ionophore could induce acrosome reaction in spermatozoa and
      that acrosome-reacted sperm cells showed obvious darkness in the head region,
      whereas acrosome-intact sperm displayed bright fluorescence over the entire sperm
      head. The basic response and pattern of acrosome reaction status were
      significantly similar in both CTC and FITC assays and in both treatment
      (genistein and beta-lapachone) groups. It was observed that higher doses of both
      genistein and beta-lapachone significantly suppressed acrosome reaction and that
      this inhibitory effect was both dose- and time-dependent. It was stipulated that
      the observed genistein inhibition of acrosome reaction could be due to
      suppression of protein kinase C, and that beta-lapachone could inhibit acrosome
      reaction through direct cytotoxic effects on sperm cell membrane at higher doses.
      However, light microscopic examination indicated that both phytochemicals had no
      significant effect on sperm morphology. It is concluded that, in view of the fact
      that acrosome reaction is a physiological prerequisite for fertilization of most
      mammalian eggs, both genistein and beta-lapachone could potentially suppress male
      fertility via suppression of acrosome reaction at higher doses, but could enhance
      fertility by promoting acrosome reaction at lower doses. This bimodal mode of
      action of both phytochemicals could offer a potentially new dimension in the
      search for causes of male infertility and possibly for male contraceptive
      development.

PMID- 14585184
TI  - Cinnamate supplementation enhances hepatic lipid metabolism and antioxidant
      defense systems in high cholesterol-fed rats.
AB  - This study investigated the effect of cinnamate, a phenolic compound found in
      cinnamon bark and other plant materials, on lipid metabolism and antioxidant
      enzyme activities in rats fed a high cholesterol diet. Three groups of rats were
      given a diet containing 1 g of cholesterol/kg for 6 weeks. The control group only
      received the high cholesterol diet, whereas the other two groups received a diet
      supplemented with lovastatin or cinnamate (0.1 g/100 g of diet). The plasma high
      density lipoprotein-cholesterol levels were significantly higher in the cinnamate
      group than in either the control or lovastatin groups, and the atherogenic index
      was significantly lower in rats with cinnamate supplementation. Supplementation
      with cinnamate resulted in significantly lower hepatic cholesterol and
      triglyceride levels. Accumulation of hepatic lipid droplets was higher in the
      control group than in the rats supplemented with either cinnamate or lovastatin.
      Hepatic 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase activity was
      significantly lower in the cinnamate group compared with the other groups,
      whereas only acyl-CoA:cholesterol acyltransferase activity was significantly
      lower in the lovastatin group compared with the control group. Cinnamate
      supplementation resulted in higher catalase and glutathione peroxidase
      activities, while hepatic thiobarbituric acid-reactive substances were
      significantly lower in both the cinnamate and lovastatin groups. The fecal acidic
      sterol was higher in the lovastatin group than in the control or cinnamate
      groups. These results suggest that dietary cinnamate inhibits hepatic HMG-CoA
      reductase activity, resulting in lower hepatic cholesterol content, and
      suppresses lipid peroxidation via enhancement of hepatic antioxidant enzyme
      activities.

PMID- 14585187
TI  - Effects of vitamin E on renal dysfunction in chronic cadmium-poisoned rats.
AB  - Cadmium is a highly toxic metal that can be ingested or inhaled from a variety of
      industrial and dietary sources. The purpose of this study was to investigate the
      effects of vitamin E on renal dysfunction and blood pressure changes in chronic
      cadmium-poisoned rats. Sprague-Dawley rats weighing 100 +/- 10 g were randomly
      assigned to one control group and three cadmium-poisoned groups. Cadmium groups
      were assigned to dietary groups according to levels of vitamin E supplementation:
      vitamin E-free diet (Cd-0E group), 40 mg of vitamin E/kg of diet (Cd-40E group),
      and 400 mg of vitamin E/kg of diet (Cd-400E group). The animals were raised for
      20 weeks, and cadmium was supplied in the drinking water at 50 ppm Cd(2+). The
      morphological changes observed by both light and electron microscopy revealed
      mitochondria and tubule epithelial cell edema in the Cd-0E group, yet this was
      alleviated with the highest level of vitamin E supplementation (Cd-400E group).
      The urinary beta(2)-microglobulin levels indicated that glomerular injury was
      higher in the Cd-poisoned groups than in the control group, but were lowered by
      vitamin E supplementation. Although the glomerular filtration rate (GFR) of the
      Cd-0E group was significantly lower than that of the control group, the vitamin E
      supplemented groups exhibited a similar GFR to the control group, suggesting that
      vitamin E protected the kidney from functional damage. Angiotensin converting
      enzyme activity, and blood pressure, and heart rate were all significantly higher
      in the Cd-poisoned group, but each remained nearly normal with vitamin E
      supplementation. Accordingly, these results indicate that vitamin E
      supplementation in chronic cadmium-poisoned rats normalized renal dysfunction and
      blood pressure regulation.

PMID- 14585188
TI  - Cholestanol metabolism, molecular pathology, and nutritional implications.
AB  - Cholestanol, not cholesterol, is a minor component in the human body and in
      foods, but an increase in cholestanol concentration in serum induces a
      pathological condition named cerebrotendinous xanthomatosis (CTX). In our
      investigation of this disease for more than 25 years, a procedure for
      quantification of cholestanol by high-performance liquid chromatography and an
      assay method for sterol 27-hydroxylase were established, and several mutations of
      the CYP 27 gene in 10 CTX families were identified. We also established
      experimental animal models with symptoms of CTX by feeding a high cholestanol
      diet. Corneal dystrophy and gallstones were produced in mice, and an apoptosis of
      cerebellar neuronal cells was observed in rats. We propose the following
      underlying mechanism of CTX pathogenesis: When cholesterol in the plasma membrane
      is replaced by cholestanol to some extent, the membrane fluidity is reduced, and
      the calcium channel fails to open, inducing cell death. CTX patients are treated
      with oral administration of chenodeoxycholic acid, which reduces the cholestanol
      concentration in serum. Cholestanol has a toxic effect, and an imbalance of the
      cholesterol/cholestanol ratio in plasma membrane is suspected to cause the
      disturbance of calcium channel function of the membrane.

PMID- 14585189
TI  - A new in vitro assay of cholesterol adsorption by food and microbial
      polysaccharides.
AB  - The adsorption of total cholesterol by polysaccharides was measured in vitro by
      enzymatic reactions, including the polysaccharide precipitation procedure. Total
      cholesterol adsorption capacities, in a mixture of polysaccharide and total
      cholesterol, were compared for apple pectin, gelrite gellan gum, xanthan gum,
      high-methoxyl pectin, citrus pectin, high-viscous alginate, low-viscous alginate,
      dextran, and zooglan. Acidic polysaccharides such as pectins, alginate, and
      xanthan gum at concentrations of 0.1% (wt/vol) were able to adsorb over 90% of
      the total cholesterol when dissolved in distilled water, sodium acetate buffer
      (pH 4.6), or sodium phosphate buffer (pH 7.0). However, total cholesterol
      adsorptions by gellan and zooglan were dependent upon the salt concentration and
      pH value, which decreased cholesterol adsorption in the following order by
      degree: distilled water, acidic pH, and alkaline pH. In particular, total
      cholesterol adsorption of zooglan was greatly decreased by the addition of sodium
      chloride. With 0.1% (wt/vol) polysaccharide dissolved in distilled water, the
      adsorption capacities of alginate, pectins, gellan gum, xanthan gum, and zooglan
      were 2.9, 2.88, 2.5, 2.9, and 2.4 mg/dL, respectively. However, 0.2% of zooglan
      was able to completely adsorb the cholesterol (3 mg/dL), whereas dextran did not
      adsorb cholesterol at all, producing no precipitate with
      hexadecyltrimethylammonium bromide.

PMID- 14585190
TI  - Intravenous and intrapulmonary administration of honey solution to healthy sheep:
      effects on blood sugar, renal and liver function tests, bone marrow function,
      lipid profile, and carbon tetrachloride-induced liver injury.
AB  - Safety of intravenous (i.v.) or intrapulmonary administration of different
      concentrations of honey and their effects on blood sugar, renal and liver
      function tests, bone marrow function, lipid profile, and carbon tetrachloride
      (CCl(4))-induced liver damage were studied. Healthy sheep of either sex, 6-8
      months old, were assigned randomly into the following groups: sheep received i.v.
      infusion of 5% honey in normal saline at 10-day intervals for 50 days and were
      compared with sheep that received 5% dextrose; sheep received higher doses of
      honey (50 g of honey) by i.v. infusion daily for 10 days; sheep received four
      higher doses of honey (80 g each dose) for 2 weeks; sheep received subcutaneous
      injection of CCl(4) after four doses of i.v. infusion of 80 g of honey, and
      estimations of serum gamma-glutamyl transpeptidase (SGGT), serum glutamic
      oxaloacetic transaminase (SGOT), and serum glutamate pyruvate transaminase (SGPT)
      were performed daily for 10 days postinjection; sheep received i.v. infusion of
      40 g of honey, and blood sugar estimation was performed for 3 h at 30-min
      intervals after infusion and compared with sheep that received 5% dextrose; sheep
      received rapid i.v. injection of 40% honey or 40% dextrose, and blood sugar was
      estimated before and after injection; sheep received various concentrations of
      honey in distilled water (0.5 mL/1.5 mL, 0.75 mL/1.75 mL and 1.2 mL/2.2 mL), and
      blood sugar estimation was performed before and after inhalation. Results showed
      that i.v. or intrapulmonary administration of honey did not cause any adverse
      effect. Intravenous delivery of honey by slow infusion caused improvement of
      renal and hepatic function, bone marrow function, and lipid profile. It reduced
      SGOT, SGPT, triglyceride, cholesterol, blood urea nitrogen, and blood sugar and
      elevated serum protein, serum albumin, hemoglobin, white blood cell, and
      neutrophil percentage. Similar results were obtained with the use of higher doses
      of honey. CCl(4) caused mild elevation of SGPT and SGGT and lowering of SGOT in
      sheep that received repeated i.v. administration of honey before administration
      of CCl(4), whereas in control sheep CCl(4) caused significant elevation of all
      the liver enzymes. Intravenous infusion of 40 g of honey caused elevation of
      blood sugar for 90 min postinfusion, whereas it decreased blood sugar at 2 and 3
      h postinfusion as compared with fasting blood sugar. Dextrose caused significant
      elevation of blood sugar at all time intervals. Similar results were obtained
      with the use of 10% dextrose or 80 g of honey. Addition of honey to dextrose
      caused less hyperglycemia as compared with dextrose alone. Acute injection of 20
      mL of 40% dextrose significantly elevated blood sugar for 3 h postinjection,
      whereas little elevation in blood sugar was obtained after injection of 40%
      honey; the difference between honey and dextrose was significant. Inhalation of
      honey caused significant lowering of blood sugar during and after inhalation as
      compared with fasting blood sugar and water inhalation. The effect was greater
      with a higher concentration of inhaled honey. It might be concluded that slow
      i.v. infusion or rapid i.v. injection of honey in different concentrations was
      safe and could lower blood sugar and improve renal, hepatic, and bone marrow
      functions and lipid profile. Intravenous honey had a hepatoprotective effect
      against CCl(4)-induced liver injury. Inhaled honey was safe and reduced blood
      sugar significantly.

PMID- 14585191
TI  - Evaluation of hydroxyl radical-scavenging abilities of silica hydride, an
      antioxidant compound, by a Fe2+-EDTA-induced 2-hydroxyterephthalate fluorometric
      analysis.
AB  - The hydroxyl radical scavenging capacity and efficacy of a novel organosiliceous
      anionic hydride compound, silica hydride, were quantified by a recently developed
      method. The method measures a direct relationship between the hydroxyl radical
      scavenging capability of the antioxidant compound and the linear decrease in
      signal from a fluorescent 2-hydroxyterephthalate product created by reacting an
      Fe(2+)-EDTA complex in the presence of a potential radical scavenger. A
      fluorescence signal half-inhibition, IC(50), value of 1.4 +/- 0.1 muM was
      obtained for silica hydride compounds. The validity of the analysis was verified
      by electron spin resonance spectroscopy, spectrophotometric analysis of
      NAD(+)/NADH ratios, mitochondrial membrane potential measurements, and assays of
      both cytochrome c (Fe(3+)) to cytochrome c (Fe(2+)) and epinephrine to
      adenochrome reductions.

PMID- 14585192
TI  - Antioxidant action of Moringa oleifera Lam. (drumstick) against antitubercular
      drugs induced lipid peroxidation in rats.
AB  - The protective effect of Moringa oleifera Lam. (Moringaceae) on hepatic marker
      enzymes, lipid peroxidation, and antioxidants was investigated during
      antitubercular drug (isoniazid, rifampicin, and pyrazinamide)-induced toxicity in
      rats. Enhanced hepatic marker enzymes and lipid peroxidation of antitubercular
      drug treatment was accompanied by a significant decrease in the levels of vitamin
      C, reduced glutathione, superoxide dismutase, catalase, glutathione peroxidase,
      and glutathione S-transferase. Administration of Moringa oleifera extract and
      silymarin significantly decreased hepatic marker enzymes and lipid peroxidation
      with a simultaneous increase in the level of antioxidants. We speculate that
      Moringa oleifera extract exerts its protective effects by decreasing liver lipid
      peroxides and enhancing antioxidants.

PMID- 14585193
TI  - Effect of Piper betle leaf extract on alcoholic toxicity in the rat brain.
AB  - The protective effect of Piper betle, a commonly used masticatory, has been
      examined in the brain of ethanol-administered Wistar rats. Brain of ethanol
      treated rats exhibited increased levels of lipids, lipid peroxidation, and
      disturbances in antioxidant defense. Subsequent to the experimental induction of
      toxicity (i.e., the initial period of 30 days), aqueous P. betle extract was
      simultaneously administered in three different doses (100, 200, and 300 mg kg(
      1)) for 30 days along with the daily dose of alcohol. P. betle coadministration
      resulted in significant reduction of lipid levels (free fatty acids, cholesterol,
      and phospholipids) and lipid peroxidation markers such as thiobarbituric acid
      reactive substances and hydroperoxides. Further, antioxidants, like reduced
      glutathione, vitamin C, vitamin E, superoxide dismutase, catalase, and
      glutathione peroxidase, were increased in P. betle-coadministered rats. The
      higher dose of extract (300 mg kg(-1)) was more effective, and these results
      indicate the neuroprotective effect of P. betle in ethanol-treated rats.

PMID- 14585194
TI  - Antioxidant activities of rosemary, sage, and sumac extracts and their
      combinations on stability of natural peanut oil.
AB  - The antioxidant efficacy of rosemary (Rosmarinus officinalis L.), sage (Salvia
      fruticosa L.), and sumac (Rhus coriaria L.) extracts and combinations at 4%
      concentrations (wt/vol, extract/oil) were investigated. Methanolic extracts of
      rosemary, sage, sumac, and their combinations were applied to peanut oil stored
      at 80 degrees C for 24 h. The antioxidant effect was determined by measuring the
      peroxide value. All extracts showed antioxidant effects compared with control.
      But the antioxidant effect of all extracts was low compared with that of
      butylated hydroxytoluene. Rosemary extract (except for 3 and 4 h) exhibited the
      most antioxidant effect compared with other individual extracts. Of blends, the
      most effective ones were sage plus sumac combinations. Sumac extract is also
      promising as a source of natural antioxidants.

PMID- 14585196
TI  - Proteasome-mediated degradation of RNase L in response to phorbol-12-myristate-13
      acetate (PMA) treatment of mouse L929 cells.
AB  - 2'-5' Oligoadenylate (2-5A)-dependent RNase L is one of the key enzymes involved
      in the molecular mechanisms of interferon (IFN) function. Although the regulation
      of RNase L by 2-5A has been studied extensively, relatively little is known about
      how RNase L is controlled by posttranslational processes. Here, we report that
      phorbol-12-myristate-13-acetate (PMA) treatment of mouse L929 fibroblasts caused
      rapid degradation of RNase L in a dose-dependent and time-dependent manner. RNase
      L levels were decreased to 40% of control levels after only 5 min exposure of
      cells to PMA, suggesting the involvement of protein kinase C (PKC). After PMA
      treatment for 1 h, RNase L levels decreased to 18% of the pretreatment levels.
      Decay of RNase L was measured by 2-5A binding assay, ribonuclease activity, and
      protein levels in Western blots probed with antibody to murine RNase L. PMA
      treatment caused decreases in the levels of RNase L in both cytoplasm and
      nucleus. To explore the mechanism of RNase L degradation, we treated cells with
      the selective proteasome inhibitors, ALLN, MG132, and PSI, prior to PMA
      treatment. These inhibitors completely blocked the degradation of RNase L caused
      by PMA. Our results show a novel regulatory pathway for RNase L that could have
      an impact on its antitumor and antiviral functions.

PMID- 14585195
TI  - Increased interleukin-10 mRNA stability in melanoma cells is associated with
      decreased levels of A + U-rich element binding factor AUF1.
AB  - Abnormal production of interleukin-10 (IL-10) is observed in some pathologic
      conditions. For example, compared with normal melanocytes, IL-10 expression is
      elevated in melanoma cells. IL-10 overexpression could inhibit both immune
      surveillance and tumor rejection. We investigated a potential posttranscriptional
      mechanism for IL-10 overexpression in melanoma cells. In normal melanocytes, the
      half-life of IL-10 mRNA is 7 min, whereas in the melanoma cell line MNT1, the
      half-life is 75 min. This 10-fold difference could account, at least in part, for
      IL-10 overexpression in MNT1 cells. Examination of the 3'-untranslated region (3'
      UTR) of IL-10 mRNA revealed a suspected A + U-rich element (ARE) that might
      target the mRNA for rapid degradation. Transfection experiments confirmed that
      these sequences promote rapid degradation when inserted into a normally stable
      mRNA, indicating ARE functionality. As AREs act via their interactions with ARE
      binding proteins, we examined cytoplasmic proteins from normal melanocytes and
      MNT1 cells for IL-10 ARE-binding activity. Compared with cytoplasmic extracts of
      normal melanocytes, cytoplasmic extracts of MNT1 cells possess substantially less
      ARE-binding activity, consistent with the extended half-life of IL-10 mRNA in
      MNT1 cells. Finally, we find that the ARE-binding protein AUF1 comprises the
      major ARE-binding activity in cytoplasmic extracts of normal melanocytes. By
      contrast, AUF1 is not detectable in cytoplasmic extracts of MNT1 cells but
      appears restricted to the nuclear fraction. Together, these data suggest a
      mechanism whereby reduced cytoplasmic levels of AUF1 in MNT1 melanoma cells may
      lead to IL-10 overexpression, with deleterious consequences for tumor
      surveillance and rejection.

PMID- 14585197
TI  - Aging is associated with increased human T cell CC chemokine receptor gene
      expression.
AB  - Leukocyte chemokine receptors (CR) are central to the pathogenesis of many human
      diseases, including human immunodeficiency virus-1 (HIV-1) infection. Elderly
      individuals infected with the HIV-1 virus have a shorter disease-free interval
      and worse clinic outcome. However, the reasons for this are unclear. We recently
      reported increased CC chemokine receptor (CCR) expression in CD4+ T cells in aged
      mice, but it is not known if similar changes occur in humans. In addition, it is
      unclear if the observed differences are related to aged-related expansion in the
      memory T cell compartment. In this report, we examined the effects of aging on
      CCR gene expression in human peripheral blood mononuclear cells (PBMCs), CD4+ T
      cells, and naive/memory T cells. Aging is found to be associated with increased
      CCR1-5 expression in PBMCs and CD4+ T cells. In addition, although the age
      related increases in CCR expression occurred in both naive and memory T cells,
      the greatest changes were seen in the memory T cell subset. We propose that the
      observed aging-associated increase in T cell chemokine receptor expression may
      contribute to the worse clinical outcome of T cell chemokine receptor-dependent
      disease, such as HIV-1 infection, in the elderly.

PMID- 14585198
TI  - Porcine TLR2 and TLR6: identification and their involvement in Mycoplasma
      hyopneumoniae infection.
AB  - We successfully cloned and sequenced porcine toll-like receptor (TLR2) and TLR6
      cDNA from porcine alveolar macrophages stimulated with 10 microg/ml
      lipopolysaccharide (LPS). The open reading frames (ORFs) of the porcine TLR2 and
      TLR6 cDNA were shown to be 2358 and 2391 bp in length and to encode 785 and 796
      amino acids, respectively. The predicted amino acid sequence of porcine TLR2 was
      72.3% homologous to human TLR2 and 61.0% homologous to murine TLR2. That of
      porcine TLR6 was 74.4% homologous to human TLR6 and 66.1% homologous to murine
      TLR6. Porcine TLR2 and TLR6 genes were both mapped to porcine chromosome 8 (TLR2:
      SSC8q21.1 --> 21.5; TLR6: SSC8p11.1 --> p21.1) by fluorescence in situ
      hybridization (FISH) and radiation hybrid mapping. Western blot analysis
      confirmed that TLR2 and TLR6 proteins were both expressed in porcine alveolar
      macrophages. Further, antiporcine TLR2 and TLR6 antibodies synergistically
      blocked tumor necrosis factor-alpha (TNF-alpha) production by porcine alveolar
      macrophages stimulated with Mycoplasma hyopneumoniae. These results indicated
      that both TLR2 and TLR6 are important in the recognition of M. hyopneumoniae in
      porcine alveolar macrophages and will be useful in understanding innate immunity
      against M. hyopneumoniae.

PMID- 14585199
TI  - IFN-gamma-inducible chemokines enhance adaptive immunity and colitis.
AB  - T helper type 1 (Th1) cells secreting interferon-gamma (IFN-gamma) have been
      closely associated with Crohn's disease (CD). Monokine-induced by IFN-gamma
      (MIG), IFN-gamma-inducible T cell alpha chemoattractant (I-TAC), and IFN-gamma
      inducible protein-10 (IP-10), are chemokines that bind CXCR3 and mediate the
      chemotaxis of leukocytes. IP-10, MIG, and CXCR3 have been shown to be expressed
      at sites of CD. The current study stems from our recent findings that IP-10, MIG,
      and I-TAC significantly contribute to the development of Th1-mediated
      inflammatory responses. To better understand the role of CXCR3 interactions
      during CD, we characterized the effects of IP-10, MIG, I-TAC, and CXCR3+ T cells
      on mucosal immune responses. IP-10, MIG, and I-TAC significantly enhanced antigen
      specific serum and mucosal antibodies through Th1-mediated events and CD28
      modulation. Additionally, the adoptive transfer of naive CXCR3+ T cells and
      CD4+CD45RB(HI) to T cell receptor beta (TCRbeta) x delta(-/-) mice resulted in
      the onset of murine colitis. Taken together, these studies suggest that IP-10,
      MIG, I-TAC, and CXCR3 interactions are involved in mucosal immune responses
      required for the induction of CD.

PMID- 14585200
TI  - Atlantic salmon interferon genes: cloning, sequence analysis, expression, and
      biological activity.
AB  - In this work, we report cDNA cloning of two type I interferons (IFNs) from the
      head kidney of Atlantic salmon, called SasaIFN-alpha1 (829 bp) and SasaIFN-alpha2
      (1290 bp). Both translate into 175 amino acid precursor molecules showing 95%
      amino acid sequence identity. The precursors have a putative 23 amino acid signal
      peptide, which suggests that the mature Atlantic salmon IFNs contain 152 amino
      acids (18.2 kDa). Salmon IFN appears to have five alpha-helices, similar to
      mammalian and avian type I IFNs, and showed 45% sequence identity with zebrafish
      IFN, up to 29% identity with mammalian IFN-alpha sequences, and 17%-18% sequence
      identity with mammalian IFN-beta and chicken type I IFNs. Human embryonic kidney
      293 cells transfected with the SasaIFN-alpha1 cDNA gene produced high titers of
      acid-stable antiviral activity, which protected salmonid cells against infectious
      pancreatic necrosis virus (IPNV) and also induced Mx protein in the cells.
      Poly(I)-poly(C) induced two IFN transcripts in head kidney of Atlantic salmon.
      Genomic IFN sequences contained four introns and five exons, which is different
      from the intronless type I IFN genes of birds and mammals.

PMID- 14585202
TI  - HIV type 1 incidence estimates by detection of recent infection from a cross
      sectional sampling of injection drug users in Bangkok: use of the IgG capture BED
      enzyme immunoassay.
AB  - Development of serologic tests to detect recent HIV-1 infection has generated
      worldwide interest in applying this approach to estimate incidence. We previously
      devised an IgG-capture BED-EIA (or BED-CEIA) that detects increasing levels of
      anti-HIV IgG following seroconversion to identify recent infection and to
      estimate incidence among persons infected with diverse HIV-1 subtypes worldwide.
      Injection drug users (IDUs; n = 1969) were screened in 1996 for participation in
      a prospective cohort study. Serum specimens from 594 IDUs were HIV-1 seropositive
      (30.2%) and were tested with the BED-CEIA. The proportion of recent infections
      and estimated incidence by different epidemiological risk factors were compared
      with incidence data measured from the prospective cohort. Of 594 HIV-1
      seropositive specimens, 113 (19%) were identified as recent infections. Overall,
      the estimated annual incidence among persons screened was 17.3%/year (95% CI,
      12.8-24.2%/year) compared with 9.0%/year (95% CI, 6.7-11.9%/year) measured from
      the prospective cohort during the same time period. Estimated incidence was
      higher among younger aged and unemployed IDUs as well as among those who injected
      more frequently, confirming previously reported risk factors from this
      prospective cohort. As persons screened from a cross-sectional sampling probably
      have higher risk for HIV than selected uninfected individuals who choose to
      participate and receive risk reduction counseling in a longitudinal cohort study,
      use of this or other serologic testing strategies to identify populations with
      high incidence (such as for HIV vaccine trials) may overestimate incidence
      measured from prospective cohorts.

PMID- 14585203
TI  - Human immunodeficiency virus in Uzbekistan: epidemiological and genetic analyses.
AB  - This study investigates the molecular epidemiology of HIV in Uzbekistan--a former
      Soviet Union (FSU) country located in central Asia. A total of 18,910,370
      subjects were involved in an HIV serological examination through a population
      survey conducted in 1987-2002. Rapid changes in epidemiological dynamics and
      transmission modes have been observed since 1999: incidence rose from 25 newly
      HIV-infected subjects per year to more than 100 new cases per month within the
      first half of 2002, and the rate of intravenous drug use (IVDU)-associated HIV
      infection increased to 75% per year during the same period. Thirty HIV-1 strains,
      isolated from specimens obtained in 1999-2000, were directly sequenced in the env
      region. Phylogenetic analysis revealed a relationship to genotype A in 56.7%, and
      to 03_CRFAB in 13.3%; both variants have been previously reported in the FSU. The
      majority (85.7%) of these strains were isolated from IVDUs. The demographic
      history of the most prevalent HIV strain in Uzbekistan was inferred from
      reconstructed molecular phylogenies; exponential growth of the viral population
      size was thus observed to occur after the mid-1990s. In summary, detectable HIV
      seroprevalence remains low in the general population of Uzbekistan. However, the
      current study demonstrates a substantially increasing number of new infections,
      in association with IVDU, and an exponentially growing effective population size
      of the IVDU-associated HIV strain.

PMID- 14585204
TI  - Gynecomastia in HIV-infected patients receiving antiretroviral therapy.
AB  - Thirty-four HIV-positive men with gynecomastia were seen in an HIV outclinic
      during a 20-month period (incidence of 2.4 cases/100 patients receiving HAART per
      year). It developed mainly in subjects having good immunologic and virologic
      status, after an average of 3 years of HAART. No hormone abnormalities were
      found, or association with specific drugs. Although initially unilateral, more
      than half of cases progressed to bilateral gynecomastia. Spontaneous resolution
      occurred in most subjects with 12 months without modifying therapy.

PMID- 14585205
TI  - Drug resistance profiles of recombinant reverse transcriptases from human
      immunodeficiency virus type 1 subtypes A/E, B, and C.
AB  - We have expressed purified recombinant reverse transcriptase (RT) from clinical
      isolates of human immunodeficiency virus subtypes B, C, and A/E in Escherichia
      coli. The drug sensitivities of these RTs were then determined for both
      nucleoside RT inhibitors (NRTIs) and nonnucleoside RT inhibitors (NNRTIs) in cell
      free RT assays. Although A/E and C viruses contained numerous polymorphisms
      relative to subtype B (i.e., naturally occurring variations unrelated to drug
      resistance), the wild-type enzymes prepared from these or subtype A/E clinical
      isolates displayed <2-fold differences in drug sensitivities with regard to the
      active triphosphate active forms of NRTIs, as compared with RT expressed from BH
      10 recombinant virus. Recombinant RTs from clinical isolates of subtypes B, C,
      and A/E that contained multiple resistance-associated mutations displayed
      expected variations in levels of resistance to the intracellular active forms of
      3TC, ddI, ddC, and PMPA, that is, 3TCTP, ddATP, ddCTP, and PMPApp, respectively.
      Subtype A/E and C RT enzymes contained only minor NNRTI polymorphisms that
      distinguished them from wild-type subtype B enzymes and wild-type RTs from these
      various subtypes showed only 1- to 4-fold variability in IC(50) values for each
      of nevirapine (NVP), delavirdine (DLV), efavirenz (EFV), and calanolide A. In
      contrast, RT enzymes from subtype B and C viruses harboring specific NNRTI
      mutations were highly resistant to all four tested NNRTIs. Subtype C variants
      containing the novel V106M resistance codon showed cross-resistance to all
      approved NNRTIs in cell-free RT assays.

PMID- 14585206
TI  - Microglia from mice transgenic for a provirus encoding a monocyte-tropic HIV type
      1 isolate produce infectious virus and display in vitro and in vivo upregulation
      of lipopolysaccharide-induced chemokine gene expression.
AB  - A large body of evidence has indicated that microglia are the predominant
      cellular location for HIV-1 in the brains of HIV-1-infected individuals and play
      a direct role in the development of HIV-1-associated dementia (HAD). Therefore,
      investigation of the mechanism by which HIV-1-infected microglia contribute to
      the development of HIV-associated dementia should be facilitated by the creation
      of a mouse model wherein microglia carry replication-competent HIV-1. To
      circumvent the inability of HIV-1 to infect mouse cells, we developed a mouse
      line that is transgenic for a full-length proviral clone of a monocyte-tropic HIV
      1 isolate, HIV-1(JR-CSF) (JR-CSF mice), whose T cells and monocytes produce
      infectious HIV-1. We detected expression of the long terminal repeat-regulated
      proviral transgene in the microglia of these transgenic mice and demonstrated
      that it was increased by in vitro and in vivo stimulation with
      lipopolysaccharide. Furthermore, microglia isolated from JR-CSF mouse brains
      produced HIV-1 that was infectious in vitro and in vivo. We examined the effect
      that carriage of the HIV-1 provirus had on chemokine gene regulation in the
      brains of these mice and demonstrated that MCP-1 gene expression by JR-CSF mouse
      microglia and brains was more responsive to in vitro and in vivo stimulation with
      lipopolysaccharide than were microglia and brains from control mice. Thus, this
      study indicates that the JR-CSF mice may represent a new mouse model to study the
      effect of HIV-1 replication on microglia function and its contribution to HIV-1
      associated neurological disease.

PMID- 14585207
TI  - Additive activity between the trans-activation response RNA-binding protein,
      TRBP2, and cyclin T1 on HIV type 1 expression and viral production in murine
      cells.
AB  - Tat-mediated trans-activation of the HIV-1 long terminal repeat (LTR) occurs
      through the phosphorylation of the carboxy-terminal domain of the RNA polymerase
      II. The kinase complex, pTEFb, composed of cyclin T1 (CycT1) and CDK9, mediates
      this process. The trans-activation response (TAR) RNA-binding protein 2 (TRBP2)
      increases HIV-1 LTR expression through TAR and protein kinase R (PKR) binding,
      but not through interactions with the Tat-CycT1-CDK9 complex. TRBP2 and the Tat
      CycT1-CDK9 complex have overlapping binding sites on TAR RNA. TRBP2 and CycT1
      increased Tat trans-activation in NIH 3T3 cells with additive effects. Upon
      transfection of HIV-1 pLAI, pNL4-3, pMAL, and pAD molecular clones, reverse
      transcriptase (RT) activity and p24 concentration were decreased 200- to 900-fold
      in NIH 3T3 cells compared with HeLa cells in both cells and supernatants. In
      murine cells, cotransfection of the HIV clones with CycT1 or TRBP2 increased
      modestly the expression of RT activity in cell extracts. The analysis of Gag
      expression in murine cells transfected with CycT1 compared with human cells
      showed a 20-fold decrease in expression and a strong processing defect. The
      expression of both CycT1 and TRBP2 had a more than additive activity on RT
      function in cell extracts and on viral particle production in supernatant of
      murine cells. These results suggest an activity of CycT1 and TRBP2 at different
      steps in HIV-1 expression and indicate the requirement for another
      posttranscriptional factor in murine cells for full HIV replication.

PMID- 14585208
TI  - Polymorphisms in p1-p6/p6* of HIV type 1 can delay protease autoprocessing and
      increase drug susceptibility.
AB  - Maturation of infectious human immunodeficiency virus type 1 (HIV-1) particles
      requires proteolytic cleavage of structural polyproteins by viral protease.
      Inhibition of protease is a powerful tool for the treatment of HIV infection.
      Using a well-established phenotypic drug susceptibility assay, we found that
      sequences outside of the protease gene can modulate the susceptibility to
      protease inhibitors (PIs). Chimeric viruses carrying p1-p6/p6* sequences from
      patient isolates in the context of an NL4-3 molecular clone exhibited increased
      PI susceptibility. Furthermore, this phenotype was associated with a delay in
      protease autoprocessing in virions and a reduction in replication capacity. We
      propose that the interplay between protease and the C terminus of Gag is critical
      for proper protease activity and mismatches between these regions can reduce
      viral replication and increase drug susceptibility.

PMID- 14585209
TI  - Binding and neutralization activity of human IgG1 and IgG3 from serum of HIV
      infected individuals.
AB  - The IgG1 and IgG3 subclasses represent the predominant antibody response to viral
      infections, including HIV. IgG subclasses differ in their interaction with
      antigen and functional effects due to specific physiochemical features. With an
      elongated hinge, IgG3 antibodies tend to have more segmental flexibility, which
      can render the antibody more effective at interacting with antigen. We have
      previously shown that the change of the human anti-CD4-binding site monoclonal
      antibody F105 from IgG1 to IgG3 results in neutralization of a T cell line
      adapted isolate (TCLA) resistant to neutralization by the parental IgG1. In the
      studies presented here, we have purified IgG1 and IgG3 subclasses from the sera
      of HIV-infected individuals and tested for immunoreactivity with and
      neutralization of HIV. Purified total IgG3 tended to have less relative
      reactivity and mediated relatively poorer neutralization of either laboratory or
      primary isolates. IgG3 also tended to react relatively less well with gp160 and
      gp120 and more robustly with gp41 and p24. The contrasting results with serum, as
      opposed to F105, may result from the polyclonal nature of serum antibodies. There
      is also a failure to make a robust IgG3 response to neutralizing epitopes on
      envelope glycoproteins during natural infection. These studies suggest that the
      investigation of isotype effects on neutralization will require isotype-switched
      human monoclonal antibodies. Understanding isotype and neutralization will
      provide important data necessary for designing the most effective possible
      vaccines.

PMID- 14585210
TI  - Propagation of CD4+ T cells specific for HIV type 1 envelope gp120 from
      chronically HIV type 1-infected subjects.
AB  - HIV-specific CD4+ T cell responses, in particular to the HIV envelope antigen
      gp120, are often undetectable in the peripheral blood of HIV-infected
      individuals. The failure to detect these cells poses a significant impediment to
      studying the T cell populations that are considered to be essential for
      controlling HIV infection and has led to speculation that these cells are
      entirely depleted during HIV infection. This study was designed to test whether
      gp120-specific CD4+ T cells exist in HIV-infected subjects and can be expanded
      from peripheral blood mononuclear cells by in vitro stimulation with the gp120
      antigen, allowing better characterization of these cells. Although gp120-specific
      T cell responses were barely observed in patient cells ex vivo before antigenic
      stimulation, CD4+ T cells specific for gp120 were successfully propagated from
      the blood of each asymptomatic chronically HIV-infected subject studied. The
      dominant epitopes recognized by gp120-specific CD4+ T cells from these HIV
      infected subjects were mapped to well-conserved sites in the C1 and C2 domains of
      gp120. Two CD4+ T cell lines recognizing these two regions were subsequently
      established. The CD4+ T cell lines proliferated and produced interferon gamma in
      response to the specific epitopes, and the responses were MHC class II
      restricted. These T cell lines also exhibited cross-reactivity with gp120 from T
      cell line-adapted HIV-1 strains IIIB and MN, as well as with gp120 from primary
      isolates SF33 (subtype B), CA1 (subtype A), and CA10 (subtype A/E). The data
      demonstrate that CD4+ T cells specific for gp120 are not entirely depleted from
      the peripheral blood of chronically HIV-infected subjects; these cells are
      present in low numbers but can be expanded after antigenic stimulation in vitro.

PMID- 14585211
TI  - Specific antibody responses to vaccination with bivalent CM235/SF2 gp120:
      detection of homologous and heterologous neutralizing antibody to subtype E
      (CRF01.AE) HIV type 1.
AB  - HIV-1 CRF.AE-01 (formerly subtype E) infection is highly prevalent in Southeast
      Asia. Despite success with public health measures, the development of an
      effective CRF01.AE vaccine is critical to the control of this epidemic. Sera from
      the open-label arms of the first clinical trial of a bivalent HIV gp120 SF2/CM235
      (subtypes B and CRF.AE-01, respectively) vaccine were evaluated for the presence
      of gp120-specific binding (BAb) and neutralizing antibody (NAb). Twelve pre- and
      postvaccination sera pairs were tested for CM235 BAb; anti-gp120 CM235 BAb was
      found in all postvaccination samples. The 12 pre- and postvaccination (1 month
      after third vaccination) serum pairs were evaluated in several neutralization
      formats: heterologous T cell line adapted (TCLA) NP03/H9, homologous CM235/PBMC,
      CM235/dendritic cell, and CM235M4-C4.6/A3R5. A3R5 is a CCR5+ T cell line, and
      CM235M4-C4.6 is the homologous CM235 virus adapted to growth in A3R5 cells. All
      volunteers developed BAb, but meaningful NAb was not demonstrable against primary
      isolate CM235. Using the TCLA CRF01.AE virus NP03 in H9 cells, 9 of 12 persons
      had NAb with a geometric mean titer (GMT) of 46. The CM235M4-C4.6 virus in A3R5
      cells also detected NAb in 9 of 12 persons, with a GMT of 41. CM235M4-C4.6/A3R5
      detected NAb in two persons with negligible NAb to NP03/H9 and vice versa.
      Whether the NAb detected by the CM235M4-C4.6/A3R5 system is qualitatively
      different from those in more traditional NP03/H9 assays will require further
      study.

PMID- 14585212
TI  - Codon usage optimization of HIV type 1 subtype C gag, pol, env, and nef genes: in
      vitro expression and immune responses in DNA-vaccinated mice.
AB  - Codon usage optimization of human immunodeficiency virus type 1 (HIV-1)
      structural genes has been shown to increase protein expression in vitro as well
      as in the context of DNA vaccines in vivo; however, all optimized genes reported
      thus far are derived from HIV-1 (group M) subtype B viruses. Here, we report the
      generation and biological characterization of codon usage-optimized gag, pol, env
      (gp160, gp140, gp120), and nef genes from a primary (nonrecombinant) HIV-1
      subtype C isolate. After transfection into 293T cells, optimized subtype C genes
      expressed one to two orders of magnitude more protein (as determined by
      immunoblot densitometry) than the corresponding wild-type constructs. This effect
      was most pronounced for gp160, gp140, Gag, and Pol (>250-fold), but was also
      observed for gp120 and Nef (45- and 20-fold, respectively). Optimized gp160- and
      gp140-derived glycoproteins were processed, incorporated into virus particles,
      and mediated virus entry when expressed in trans to complement an env-minus HIV-1
      provirus. Mice immunized with optimized gp140 DNA developed antibody as well as
      CD4+ and CD8+ T cell immune responses that were orders of magnitude greater than
      those of mice immunized with wild-type gp140 DNA. These data confirm and extend
      previous studies of codon usage optimization of HIV-1 genes to the most prevalent
      group M subtype. Our panel of matched optimized and wild-type subtype C genes
      should prove valuable for studies of protein expression and function, the
      generation of subtype-specific immunological reagents, and the production of DNA
      based sub-unit vaccines directed against a broader spectrum of viruses.

PMID- 14585213
TI  - Protein binding in antiretroviral therapies.
AB  - There is marked variability in the extent to which the three classes of
      antiretroviral (ARV) drugs bind to plasma proteins (<5 to >99%). Protease
      inhibitors (PIs), with the exception of indinavir, are more than 90% protein
      bound, mainly to alpha1-acid glycoprotein (AAG). Efavirenz, a nonnucleoside
      reverse transcriptase inhibitor (NNRTI), is more than 99% bound, mainly to
      albumin. Nucleoside reverse transcriptase inhibitors (NRTIs) are not highly
      protein bound. The pharmacological activity of ARV drugs is dependent on unbound
      drug entering cells that harbor the human immunodeficiency virus (HIV). There has
      been concern that changes in protein binding could impact on antiviral activity
      and management. However, for PIs and NNRTIs, and for many drugs given orally,
      altered plasma binding would not be expected to influence the average exposure to
      unbound (active) drug after chronic oral dosing. Nevertheless, there will be a
      change in the relationship between total and unbound concentrations that will be
      important if, as part of therapeutic drug monitoring, the total rather than the
      unbound drug is measured. Measuring drug concentrations that are needed to
      inhibit different HIV strains (wild type and drug resistant) in vitro could also
      cause confusion because most methods employ bovine serum in the assay medium, and
      unbound concentrations are not directly measured. Estimating unbound drug
      concentrations in human plasma and in incubation media can be highly method
      dependent and thus may affect the calculated IC50 (the concentration of drug that
      results in 50% inhibition of viral replication). Because inhibitory quotients
      (IQs = C(trough)/IC50) are becoming part of pharmacokinetic/pharmacodynamic
      (PK/PD) analyses of clinical trial data, the strengths and weaknesses of the
      methods used for the determination of unbound drug concentration in plasma and in
      vitro systems--ultracentrifugation, ultrafiltration, and equilibrium dialysis-
      need to be understood. Consensus on standard procedures must be reached. In June
      2002, a panel of experts assembled by the Forum for Collaborative HIV Research
      met in Washington, DC, to review the basic principles of protein binding of ARV
      drugs, and to discuss the impact that changes in plasma protein binding may have
      on the PKs and activity of ARV drugs as well as on therapeutic drug monitoring.
      The purpose of the meeting was to discuss the following topics: (1) basic
      principles of protein binding and how changes in binding can impact on drug PKs
      and drug exposure in vivo, (2) variability in plasma protein binding among
      patients taking ARV drugs, (3) the impact of HIV infection and concomitant
      diseases on the extent of plasma protein binding, (4) the likelihood of
      clinically relevant drug interactions at the level of plasma protein binding, (5)
      the evidence that measuring unbound concentrations of ARV drugs in the plasma of
      patients gives more meaningful information than total drug concentration and,
      therefore, should be considered in routine therapeutic drug monitoring of ARV
      agents, (6) optimal method(s) for measuring the unbound concentration of drugs in
      vitro (for IC50 determination) and in vivo, and (7) future studies that need to
      be considered to fully understand the importance of plasma protein binding in
      therapeutic drug monitoring. This report summarizes the topics discussed at this
      meeting. It guides the reader through the discussions that allowed the panel to
      formulate a series of statements regarding the significance of plasma protein
      binding of ARV drugs when studied in vitro and in vivo. The roundtable
      participants also identified research priorities that are important for
      understanding the sources of inter- and intraindividual variability in protein
      binding in patients. These include obtaining data on unbound as well as on total
      concentrations in PK studies; looking at variants of AAG and whether they differ
      in binding affinity; and emphasizing the importance of developing a standard
      procedure for drug susceptibility assays used to determine IC50 values.

PMID- 14585215
TI  - The primary phase of infection by pathogenic simian-human immunodeficiency virus
      results in disruption of the blood-brain barrier.
AB  - Using the simian-human immunodeficiency virus (SHIV), we have investigated
      whether the blood-brain barrier (BBB) is compromised during the early stages of
      infection. Five macaques were inoculated with pathogenic SHIV(50OLNV) for 2 weeks
      at which time macaques were anesthetized, perfused with saline, and sacrificed.
      The brains were removed and examined for the disruption of the blood-brain
      barrier by immunohistochemical staining for the plasma protein fibrinogen in the
      neural parenchyma. Our results indicate a disruption of the BBB in the five of
      five macaques inoculated with SHIV(50OLNV) for 2 weeks. Zonula occludens 1 (ZO
      1), which is a marker for the tight junctions formed by brain vascular
      endothelial cells, was largely absent in areas that showed fibrinogen deposition
      in all five macaques. To determine if the BBB integrity correlated with the
      initial stages of infection, the brains from two macaques were analyzed that had
      progressed to end-stage disease following inoculation with pathogenic
      SHIV(50OLNV) but developed no neuropathology and from two macaques that were
      inoculated with a gene-deleted, nonpathogenic virus (novpuSHIV(KU-1bMC33)) for
      over 1 year. Our results indicate that unlike the macaques sacrificed during the
      acute phase of infection, immunohistochemical staining for fibrinogen in the
      neural parenchyma was negative and ZO-1 staining was readily detected in the
      endothelial cells of the blood vessels. The results of this study indicate that
      the transient loss of BBB integrity is a function of the high level of virus
      replication that occurs during the acute phase of infection and provides
      important information on the early stages of lentivirus neuroinvasion.

PMID- 14585216
TI  - Productive HIV infection of resting CD4+ T cells: role of lymphoid tissue
      microenvironment and effect of immunomodulating agents.
AB  - The ability of resting CD4+ T cells to support HIV replication is relevant to
      understanding how the reservoir of HIV-1-infected resting CD4+ T cells is
      generated, maintained and, hopefully, how it might be reduced or eliminated. We
      have utilized a tonsillar histoculture system to demonstrate that HIV,
      particularly X4 strains, can productively infect phenotypically resting CD4+ T
      cells in vitro and that this event is largely dependent on the lymphoid tissue
      microenvironment. Highly purified CD4+ tonsillar T cells that lack expression of
      both cell surface and nuclear antigens characteristic of classic T cell
      activation produce X4 HIV-1 mRNA, p24, and infectious virus while maintaining a
      resting phenotype when cultured in a tonsillar tissue microenvironment; in
      contrast, comparable purified resting CD4+ tonsillar T cells that have been
      exposed to X4 HIV do not support HIV replication when cultured in the absence of
      a lymphoid tissue microenvironment. HIV production from phenotypically resting
      CD4+ T cells is dramatically inhibited by anti-proinflammatory cytokine agents or
      immunosuppressive cytokines, but is only modestly suppressed by an inhibitor of
      the cell cycle. The ability of resting CD4+ T cells to support HIV replication in
      the microenvironment of the lymphoid tissue has implications in the pathogenesis
      of HIV disease and may provide an additional avenue for therapeutic intervention.

PMID- 14585217
TI  - Cell-free HIV type 1 infection is restricted in the human trophoblast
      choriocarcinoma BeWo cell line, even with expression of CD4, CXCR4 and CCR5.
AB  - The restriction of cell-free HIV-1 infection has been demonstrated in placental
      trophoblast choriocarcinoma BeWo cells. We tried to determine the level of the
      viral replication cycle at which this restriction occurs. BeWo cells produce
      infectious viruses after transfection with HIV-1 plasmids, independently of viral
      tropism. CCR5 and CXCR4, but not the CD4 molecule, were detected at the cell
      surface. We therefore derived CD4-expressing clones from transfected BeWo cells.
      Cell-free virus infection of these clones resulted in neither virus production
      nor viral sequence integration, indicating that the restriction occurs before
      integration of the virus. If we used luciferase reporter viruses pseudotyped with
      HIV-1 Env R5 and X4 for infection, no luciferase activity was detected, even in
      the BeWo-CD4+ clone, in contrast to what was observed in VSV-G pseudotyped virus
      infection. Our results show that infection of trophoblast-derived cells with cell
      free virus is at least restricted at the level of entry. Thus, BeWo is an
      interesting human placental cell line that is resistant to HIV-1, even if CD4,
      CXCR4, and CCR5 are expressed.

PMID- 14585218
TI  - Replication kinetics for divergent type 1 human immunodeficiency viruses using
      quantitative SYBR green I real-time polymerase chain reaction.
AB  - A quantitative and sensitive measure of human immunodeficiency virus type 1 (HIV
      1) replication is quantitative real-time polymerase chain reaction (PCR). Real
      time PCR using SYBR green I and oligonucleotide primers that amplify early,
      intermediate, and late products of reverse transcription were optimized to
      measure HIV-1 replication of clade A, B, C, and D HIV-1 isolates in peripheral
      blood lymphocytes and in both transformed and viral-transformed CD4+ lymphocyte
      cell lines. Real-time PCR can detect HIV-1 replication as early as 1 hr
      postinfection and demonstrates that in established cell lines cDNA can be
      detected as early as 4 hr postinfection. The first round of HIV-1 replication in
      established cell lines is complete between 12 and 24 hr postinfection.
      Furthermore, real-time PCR can detect HIV-1 replication in fewer than 0.1% of
      cells. Patient isolates replicated at different rates in peripheral blood
      lymphocytes, with viral cDNA peaking between 48 and 120 hr, depending on the
      virus being studied. Real-time PCR differentiated the mechanisms of action of
      drugs targeted at HIV-1 entry, reverse transcription, and proteolytic processing
      and identified differences in the kinetics of reverse transcription between
      zidovudine-sensitive and zidovudine-resistant HIV in the presence of zidovudine.
      In summary, real-time PCR using SYBR green I dye is a sensitive, quantitative,
      and reproducible measure of replication kinetics for a variety of group M HIV-1
      isolates.

PMID- 14585219
TI  - The theta-defensin, retrocyclin, inhibits HIV-1 entry.
AB  - Retrocyclin is a circular antimicrobial 18-residue peptide encoded in the human
      genome by a theta-defensin pseudogene. In the human genome, the gene for
      retrocyclin is inactivated by an in-frame stop codon in its signal sequence but
      its mature coding sequence is intact. The peptide corresponding to the processed
      human retrocyclin, generated by solid phase peptide synthesis, inhibited
      replication of R5 and X4 strains of HIV-1 in human cells. Luciferase reporter
      virus and Vpr-BLaM entry assays were used to demonstrate that retrocyclin
      specifically blocked R5 and X4 HIV-1 replication at entry. Surface plasmon
      resonance demonstrated that retrocyclin bound to soluble CD4 and gp120, but gp120
      cell-binding assays revealed that retrocyclin did not fully inhibit the binding
      of soluble CD4 to gp120. A fluorescent retrocyclin congener localized in cell
      surface patches either alone or colocalized with CD4, CXCR4, and CCR5. In the
      aggregate, these results suggest that retrocyclin blocks an entry step in HIV-1
      replication. Retrocyclin represents a new class of small molecule HIV-1 entry
      inhibitors.

PMID- 14585220
TI  - IL-12/GM-CSF coadministration in an SIV DNA prime/protein boost protocol enhances
      Gag-specific T cells but not virus-specific neutralizing antibodies in rhesus
      macaques.
AB  - Coadministration of pVecB7, a replication-defective SIV DNA vaccine, with
      interleukin-12 and GM-CSF expression plasmids, induced markedly enhanced control
      of viral replication and disease-free survival in macaques challenged
      intrarectally with pathogenic SIVsmE660. Protective mechanisms correlated with
      broader cell-mediated immune responses to the first two-thirds of the SIV Gag
      protein and possibly with enhanced SIVsmE660 antibody neutralization at set
      point, but not with pre- or early postchallenge SIVsmE660 neutralizing antibody
      production.

PMID- 14585221
TI  - Gp120-alum boosting of a Gag-Pol-Env DNA/MVA AIDS vaccine: poorer control of a
      pathogenic viral challenge.
AB  - Envelope protein immunogens may improve DNA or live-vectored HIV vaccines by
      complementing antiviral cellular responses with Env antibodies. We tested this
      concept by administering two immunizations of alum-adjuvanted HIV-1 89.6 gp120 to
      macaques being primed at weeks 0 and 8 with SHIV 89.6 Gag-Pol-Env DNA and boosted
      at week 24 with SHIV-89.6 Gag-Pol-Env recombinant modified vaccinia Ankara (MVA).
      Three hundred micrograms of gp120 was delivered with the second DNA prime and the
      MVA booster. Eight months after vaccination, all animals were challenged
      intrarectally with the related, yet serologically distinct, SHIV-89.6P. The gp120
      immunizations raised binding, but not neutralizing antibody for the challenge
      virus, and allowed testing of whether gp120 vaccines that fail to raise
      neutralizing antibody can improve protection. Following the second gp120
      immunization, the plus-gp120 group showed >10 times higher levels of binding
      antibody than the minus-gp120 group. These levels fell and were overall similar
      in both groups at the time of challenge. Following the second challenge, both
      groups had similar temporal patterns and heights of binding and neutralizing
      antibodies. However, the plus-gp120 group had less consistent control of viremia
      and higher levels of plasma viral RNA for the first year postchallenge. Assays
      for complement-dependent enhancing antibody revealed a trend toward higher levels
      of activity in the plus-gp120 group. This trend did not reach significance in our
      animal groups of 8. We conclude that gp120 inoculations that fail to raise
      neutralizing antibody do not improve the efficacy of Gag-Pol-Env DNA/MVA
      vaccines.

PMID- 14585223
TI  - Ketoconazole and lopinavir/ritonavir coadministration: boosting beyond boosting.

PMID- 14585222
TI  - A modified SCID mouse model of HIV infection with utility for testing anti-HIV
      therapies.
AB  - Using human tumor cells we have developed a mouse model of active HIV infection
      that may be used for testing antiviral agents, although it does not reflect the
      pathogenesis of human infection. Irradiated SCID/NOD mice are injected with a
      tumor of human CD4+ lymphoma cells susceptible to infection and at a separate
      site, tumor cells persistently infected with either primary or T cell line
      adapted strains of HIV. The spread of infection from the infected to the
      susceptible tumor is monitored as plasma p24 and the presence of HIV-infected
      cells in the spleen. We have used this model to examine the relative efficacy of
      neutralizing anti-HIV antibodies to halt the spread of infection. We have found
      that the tetrameric CD4-antibody fusion protein, CD4-IgG2, is highly effective
      compared to an anti-V3 loop antibody. This animal model, while not replicating
      the human disease, allows for the simultaneous testing of efficacy, toxicity, and
      pharmacokinetics of potential new antiviral therapies. The model can easily be
      powered to enable comparisons between different therapeutic agents and dosing
      regimens.

PMID- 14585224
TI  - Advances in neoadjuvant chemotherapy in soft tissue sarcomas.
AB  - The use of adjuvant chemotherapy in soft tissue sarcomas (STS) continues to be an
      area of controversy; however, the group of investigators favoring the use of an
      anthracycline- and ifosfamide-based regimen for high-risk (American Joint
      Committee on Cancer stage III) extremity STS is steadily increasing. The historic
      5-year survival rate of approximately 50% in this high-risk group treated with
      local therapy alone represents a poor standard of care, thus there is a need to
      incorporate systemic therapy early in the management of these patients. Published
      data from the meta-analysis of doxorubicin-based adjuvant chemotherapy trials and
      the prospective randomized data with epirubicin and ifosfamide from the Italian
      Sarcoma Group are frequently used as rationale for this approach. In a rare and
      heterogenous group of diseases, such as STS, physicians run into negative studies
      for various reasons that have little to do with the efficacy of the treatment
      being tested. The wisdom may be in capitalizing further on a positive lead as
      opposed to nihilism. It is appropriate to acknowledge that the chemotherapeutic
      agents have limited efficacy and are toxic, especially when used at full
      therapeutic doses. Selecting patients in whom there is some evidence of benefit,
      justifying the poor quality of life from receiving chemotherapy, becomes very
      important. This rationale, with the lessons learned from osteosarcoma research,
      forms the basis for neoadjuvant chemotherapy for STS. Until we reach the day when
      we have identified critical tumorigenic targets and their effective inhibitors
      for most of these tumors, we are obligated to use the available therapeutic
      armamentarium in the best possible sequence.

PMID- 14585225
TI  - New therapeutic strategies for soft tissue sarcomas.
AB  - The treatment of patients with metastatic soft tissue sarcomas (STS) is complex.
      There are limited agents available and many are associated with significant
      toxicity. When evaluating a patient with metastatic disease, physicians should
      ask themselves whether there is a role for surgery to render the patient free of
      disease. Combination chemotherapy in patients who have not received chemotherapy
      in the adjuvant setting is one option, particularly in a young patient with a
      good performance status. Sequential single-agent therapy for patients who are
      more elderly or debilitated by their disease may be more appropriate. Gemcitabine
      appears to be an agent with activity, particularly in patients with
      leiomyosarcomas. The data regarding prolonged gemcitabine infusions suggest
      improved activity that was predicted based on prolonged intracellular gemcitabine
      levels. Because of these data, the prolonged infusion schedule should be used. In
      addition, because of the paucity of effective agents, consideration of clinical
      trial participation for patients with newly diagnosed metastatic disease is
      appropriate, particularly in chemotherapy-insensitive histologies. The role of
      the newer agents (eg, ecteinascidin-743, epothilones, and mammalian target of
      rapamycin) is undefined. Ecteinascidin-743 has been the most extensively tested
      agent, and its ability to slow growth kinetics of a tumor and stabilize it
      clinically is intriguing. Data regarding the response to BMS-247550 will be
      published shortly and will help define the further role of epothilones in this
      disease. There is a preclinical rationale that makes the mammalian target of
      rapamycin inhibitors attractive for the treatment of muscle-derived neoplasms. In
      addition, there are cell-line data suggesting activity in rhabdomyosarcoma. These
      agents are being tested in adult STS and will likely be tested in pediatric
      histologies when there are more safety data available in that population. SU11248
      will continue to be tested in patients refractory to imatinib mesylate and may
      well prove to be another active agent for patients with gastrointestinal stromal
      tumors. As depicted by the analysis of gemcitabine efficacy, agents with activity
      in a subgroup of STS may be overlooked by the "come one come all" approach to
      clinical trials in STS. Identifying key targets in specific STS will be helpful
      in the testing of newer molecularly targeted agents. Biologic differences will
      support histology-specific trials to better understand the activity of an agent
      in a specific disease site or specifically target a biologic pathway with
      relevance to the malignant potential of the disease. For future clinical trials
      in STS to achieve the goal of histology-specific trials, cooperative group and
      multi-institutional trials will be required to obtain the appropriate patients
      with these rare histologies. It will also be increasingly important to be
      committed to obtaining tumor tissue in these patients to validate hypotheses
      regarding tumor biology and the effectiveness of therapeutic agents.

PMID- 14585226
TI  - Techniques to modulate radiotherapy toxicity and outcome in soft tissue sarcoma.
AB  - Radiotherapy (RT) targeting of soft tissue sarcoma presents considerable
      opportunity and challenges in realizing the dual goals of tissue and function
      preservation and maintaining high local control. Traditional RT target volumes
      used for soft tissue sarcoma have largely been constrained by available
      technology and are not ideal in some situations. The advent of very precise
      treatment planning and delivery systems, including three-dimensional conformal
      radiotherapy and intensity-modulated radiotherapy, means it is possible to select
      target volumes that more closely approach the optimum. Consequently, these new
      approaches provide great opportunity for treatment enhancement in the future. It
      can be expected that newer techniques for RT planning and delivery will challenge
      the existing dogma concerning target delineation for optimal radiotherapy
      outcome. It can be foreseen that the precise knowledge of appropriate targets
      will continue to evolve for different clinical scenarios and likely be greatly
      influenced by enhanced imaging capability. Advancement of three-dimensional
      conformal radiotherapy and intensity-modulated radiotherapy over the next decade
      must rely on the consistent reporting and sharing of results concerning outcome
      of normal tissue from volumetric treatment planning.

PMID- 14585227
TI  - Reconstruction for lower extremity limb salvage in soft tissue carcinoma.
AB  - Limb salvage procedures for the lower extremity have a 95% success rate and have
      essentially supplanted primary amputation as the primary treatment for limb
      threatening malignancies. En bloc tumor resection involving major neural and
      vascular structures that once led to amputation are now successfully
      reconstructed using free-tissue transfer in combination with neoadjuvant and
      adjuvant chemoradiation therapies and brachytherapy. Planning for reconstruction
      of complex lower extremity wounds begins at the time of diagnosis and extends to
      postoperative rehabilitation. Developing a successful reconstructive plan
      requires a team approach with accurate assessment of the anticipated loss of
      critical structures, wound location, defect size, and an understanding of the
      local and distant tissues available for reconstruction. Comprehensive assessment
      of the anticipated wound combined with an understanding of the distant and local
      tissues available for reconstruction allows the reconstructive surgeon to select
      tissues from the entire body that have improved functional and aesthetic outcomes
      for patients.

PMID- 14585228
TI  - Oligodendroglioma.
AB  - Oligodendroglial tumors have historically been a fatal disease, despite maximum
      medical and surgical treatment. However, in the past 10 years, effective adjuvant
      therapies have been developed that have been found to significantly prolong
      patient survival and, in some instances, provide a cure. Improvements in our
      understanding of the molecular biology of these tumors, refinements in surgical
      technique, and advances in chemotherapeutic treatment have combined to produce
      this improvement in survival with little additional toxicity to patients. At the
      time of diagnosis, patients should undergo maximum surgical resection or needle
      biopsy if maximum surgical resection is not possible. Patients with low-grade
      lesions may be followed, receiving radiation only at the time of progression.
      Patients with high-grade lesions should be irradiated up front. In addition,
      selected patients should receive chemotherapy. Clinical trials remain critical to
      advancing our understanding of these tumors and improving our ability to cure
      these patients.

PMID- 14585229
TI  - Primary central nervous system germ cell tumors.
AB  - The prognosis of primary germ cell tumors (germinal neoplasms) of the central
      nervous system varies, depending on the histology and size of tumor and the
      extent of disease at diagnosis. Although some patients receive therapy without a
      tissue diagnosis, it is strongly recommended that tumor tissue samples be
      obtained for accurate histologic diagnosis. Modern neurosurgical navigation
      techniques have made tissue sampling by stereotactic biopsy a safe and rapid
      method of determining tumor histology. Depending on tumor location, open surgical
      biopsy may be required in some patients. Typically, germinomas are exquisitely
      radiosensitive, although preirradiation chemotherapy reduces the total radiation
      exposure and may increase the cure rate. Induction cisplatin-based chemotherapy,
      followed by low-dose involved field radiotherapy, has excellent overall and
      relapse-free survival rates and is the optimal treatment for patients with
      germinomas. This combined chemoradiotherapy approach is associated with minimal
      endocrinopathy and minimal neurocognitive dysfunction. Patients with relapses
      after low-dose radiation therapy can respond well to salvage therapy
      (chemotherapy or chemoradiotherapy) without significant sequelae. Patients with
      nongerminomas respond best to chemotherapy combined with radiation, although the
      response and cure rates are lower compared to germinomas. Patients with residual
      masses and normal tumor markers after primary therapy should have a second-look
      resection because most patients have residual teratoma or necrotic tissue and can
      be spared additional chemotherapy or radiation. Pure mature teratomas are cured
      only by surgical extirpation. Immature central nervous system teratomas appear to
      benefit from radical surgical resection, but higher doses of locally directed
      radiotherapy are required with no benefit from the usual chemotherapy.

PMID- 14585230
TI  - Medulloblastomas and central nervous system primitive neuroectodermal tumors.
AB  - Significant advances in the treatment of medulloblastoma and primitive
      neuroectodermal tumors have been made in the past three decades. Maximal surgical
      resection is a mainstay of therapy. However, unlike many other central nervous
      system neoplasms, medulloblastoma and primitive neuroectodermal tumors are
      radiation and chemotherapy responsive. Despite this response, the prognosis for
      patients with these tumors remains variable and is relatively poor in infants and
      patients with metastatic disease. These tumors most commonly arise in children,
      thus most clinical trials emphasize the reduction of long-term sequelae, in
      addition to improving survival. All newly diagnosed patients who are eligible
      should be offered participation in a clinical trial. If a patient is ineligible
      or declines consent/assent for a clinical trial, the best current treatment
      approach is surgical resection, followed by radiation therapy (except for
      children younger than 3 years) with weekly vincristine. For high-risk patients,
      36 Gy of craniospinal irradiation should be delivered plus a boost of 19.8 Gy to
      the posterior fossa/primary tumor bed and sites of bulk metastatic disease. For
      average-risk patients, the craniospinal irradiation dose may be lowered to 23.4
      Gy plus 32.4 Gy to the posterior fossa/tumor bed. After radiation therapy,
      intensive multimodal chemotherapy should be used for all patients.

PMID- 14585231
TI  - Malignant spinal cord compression.
AB  - Malignant spinal cord compression is one of the most dreaded complications of
      cancer. If untreated, it can lead to worsening neurologic function culminating in
      paralysis and sphincter incontinence. The most challenging aspect in the
      management of this complication is early diagnosis because the single most
      important factor determining outcome is the level of neurologic function at
      initiation of therapy. Magnetic resonance imaging is the diagnostic modality of
      choice. Steroids have a proven role in the treatment. Radiation therapy has been
      the standard of care, with surgery reserved for special cases. A recent
      randomized trial has proven that in appropriately selected patients initial
      surgery, followed by radiation, provides better functional and neurologic outcome
      compared to radiation alone and will likely become the standard of care in the
      future. Newer modalities, such as transarterial embolization and extracranial
      stereotactic radiosurgery, are emerging and may be considered in appropriate
      cases if available.

PMID- 14585232
TI  - Ependymal tumors.
AB  - Ependymal tumors are rare malignancies that arise from the cells that line the
      ventricles and central canal of the spinal cord. Although they are more common in
      children, adults may also be effected by ependymal tumors. Prognosis is dependent
      on tumor location, histology, especially for myxopapillary tumors that tend to
      occur in the lumbar spine, extent of surgical resection, and stage of disease.
      Standard therapy consists of complete resection when feasible. The exact role of
      adjuvant radiotherapy in patients with radiographically confirmed complete
      resection is poorly defined. Patients with known residual disease may benefit
      from local radiation therapy, but the extent of radiation field and total dose
      are controversial. Even in patients treated with involved field radiotherapy,
      most relapses occur within the original tumor bed, thus local control remains the
      biggest obstacle to effective therapy. Chemotherapy has little impact against
      this tumor and has no role in the adjuvant setting, outside of a well designed
      clinical trial, with the possible exception of children younger than 5 years in
      an effort to delay radiation. A minority of patients may respond to one of
      several chemotherapy regimens at the time of recurrence, but the impact of this
      therapy is limited. Newer treatment strategies are needed.

PMID- 14585233
TI  - Antiviral Therapy for Hepatitis C.
AB  - Current treatment for hepatitis C virus infection consists of pegylated
      interferon and ribavirin. The most important predictors of response to antiviral
      therapy for HCV include genotype 2 or 3 infection, baseline viral load less than
      2 million copies/mL, and the absence of cirrhosis. Hepatitis C genotype and viral
      load should be obtained prior to initiating therapy. Liver biopsy can be used to
      stage the liver disease, to provide prognostic information, and to evaluate for
      coexisting causes of liver injury. Patients with genotype 1 infection require 48
      weeks of therapy and a ribavirin dosage of 1000 to 1200 mg/d to achieve an
      optimal response. Patients with genotype 2 or 3 infection require only 24 weeks
      of treatment and a ribavirin dose of 800 mg/d. Treatment may be discontinued in
      patients who do not have a 100-fold reduction in hepatitis C virus RNA level from
      baseline at week 12 because they are unlikely to achieve a sustained response
      with further therapy. Patients with cirrhosis and hepatic decompensation or a
      small hepatocellular carcinoma should be evaluated for liver transplantation.

PMID- 14585234
TI  - Treatment of Nonalcoholic Fatty Liver Disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) is very common in the United States, and
      in some patients it may lead to cirrhosis, liver failure, and liver cancer. NAFLD
      encompasses a spectrum of liver injury, ranging from steatosis to
      steatohepatitis, advanced fibrosis, and cirrhosis. Nonalcoholic steatohepatitis
      (NASH), an advanced form of NAFLD, histologically comprises steatosis, balloon
      degeneration, inflammation, and fibrosis in varying degrees. It is generally
      believed that simple steatosis is benign with minimal risk of progression,
      whereas NASH is progressive and can lead to cirrhosis. The commonly associated
      risk factors for NAFLD include obesity, hyperlipidemia, and diabetes mellitus.
      The pathogenesis of NAFLD and NASH is not fully known; however, current evidence
      suggests that insulin resistance and lipid peroxidation play a role in the
      pathogenesis of this condition. Currently, there are no proven effective
      therapies available for the treatment of NASH. Although there are numerous
      studies that have explored various treatments for NASH, these generally consist
      of small numbers of patients with suboptimal endpoints. Treatment strategies for
      NAFLD and NASH can be broadly divided into 1) treatment or control of underlying
      risk factors such as hyperlipidemia, diabetes mellitus, and obesity; and 2)
      specific pharmacologic therapy such as insulin sensitizers, antioxidants, or
      cytoprotective agents. Newer thiazolidinediones, such as rosiglitazone and
      pioglitazone, have shown promise in the treatment of NASH in pilot studies.
      However, these agents should not be used in clinical practice until their
      efficacy and safety are firmly established in larger studies. Despite encouraging
      initial studies, the recently completed multicenter, randomized, controlled trial
      failed to show any efficacy for ursodeoxycholic acid in the treatment of NASH.
      Other agents, such as vitamin E, betaine, probucol, and atorvastatin, have been
      explored as therapeutic agents for NASH. However, none of these studies have
      shown convincingly their utility in the treatment of NASH. Attempts to identify
      optimal therapy for patients with NASH are being vigorously pursued by the
      research community and important advances are expected within next several years.
      Until then, subjects should be advised to avoid alcohol, lose weight, and
      exercise regularly, and meticulous attention should be paid to the control of
      their risk factors such as diabetes and hyperlipidemia.

PMID- 14585235
TI  - Treatment of Hepatocellular Carcinoma.
AB  - The incidence of hepatocellular carcinoma (HCC) is increasing in the United
      States. Several modalities are available for the treatment of HCC, and decisions
      regarding the optimal choice of therapy are based on tumor burden and severity of
      liver disease. Classification systems are helpful for prognostic purposes and to
      guide in the choice of therapy. Surgical resection is a mainstay of therapy for
      patients with solitary small tumors and preserved liver function (noncirrhotic or
      Child-Pugh class A cirrhotic patients without portal hypertension).
      Unfortunately, a minority of patients is eligible for resection, and
      postoperative recurrence or de novo HCC is common. Liver transplantation offers
      the best chance of curing HCC in cirrhotic patients. Patients with a solitary
      tumor less than 5 cm or no more than three tumors each 3 cm or less have a
      survival rate of 70% with less than 20% recurrence at 5 years. Access to liver
      transplantation is limited by organ availability, and tumor progression during
      the waiting period can lead to ineligibility. Ethanol injection and
      radiofrequency ablation are effective modalities to ablate small tumors
      (generally <5 cm) in patients who are not candidates for resection or liver
      transplantation. These modalities can also be used to treat HCC prior to liver
      transplantation. Transarterial chemoembolization is used to treat patients with
      multifocal or large HCC who are ineligible for other therapies. Chemotherapeutic
      agents are infused into the tumor via the hepatic artery along with embolic
      material in order to induce tumor necrosis. This technique should be used in
      selective patients with relatively preserved liver function, absence of portal
      vein thrombosis, or encephalopathy. Limited data exist to support the use of this
      modality as a primary treatment option for small HCC. Chemotherapeutic or
      hormonal therapies have a limited role in the management of patients with HCC.
      Despite mixed outcomes, we routinely use the somatostatin analog octreotide in
      advanced, multifocal HCC. Emerging therapies should focus on treatment of small
      tumors and targeted pharmacologic therapy for advanced disease.

PMID- 14585236
TI  - Fulminant Hepatic Failure.
AB  - Fulminant hepatic failure is a rapidly progressive and often fatal syndrome, and
      the only definitive treatment is liver transplantation. However, given the
      scarcity of available grafts, the mainstay of therapy remains supportive care
      until there is spontaneous recovery or until a suitable donor liver becomes
      available. After initial assessment and stabilization, patients should be
      transferred to the nearest liver transplant center as soon as possible, as they
      can deteriorate rapidly. All patients with fulminant hepatic failure must be
      monitored closely and treated for hepatic encephalopathy, coagulopathy,
      gastrointestinal bleeding, renal failure, cerebral edema, and metabolic
      derangement.

PMID- 14585238
TI  - Management of Primary Biliary Cirrhosis.
AB  - Primary biliary cirrhosis is a chronic, progressive disease for which there is no
      definitive treatment. Ursodeoxycholic acid, however, is of benefit for delaying
      progression to irreversible end-stage liver disease and prolonging survival free
      of transplantation. It is, therefore, the standard medical therapy for primary
      biliary cirrhosis. Orthotopic liver transplantation can be offered for patients
      with end-stage disease. Other important endpoints of treatment in this condition
      include management of the long-term complications of cholestasis such as
      pruritus, osteoporosis, and fat-soluble vitamin deficiencies. Pruritus is best
      treated with cholestyramine; rifampicin, antihistaminics, opioid-antagonists, and
      ondansetron can also be tried. Osteoporosis should be treated with calcium and
      vitamin D supplementation. Bisphosphonates or vitamin K2 may be of additional
      benefit to decrease the risk of fractures, but this is unproved as of yet.
      Deficiencies of vitamins A, D, E, and K should be treated with appropriate
      replacement. Finally, orthotopic liver transplant is indicated for cases of liver
      failure, intractable pruritus, or severe osteoporosis.

PMID- 14585237
TI  - Treatment of Ascites.
AB  - Ascites is the most common complication of cirrhosis and occurs in more than half
      of all patients with cirrhosis. The development of ascites indicates progression
      of the underlying cirrhosis and is associated with a 50% 2-year survival rate.
      Conventional therapies used for the treatment of ascites include sodium
      restriction (<88 mmol/d), diuretics, and large volume paracentesis (LVP) (>5 L).
      The most effective diuretic combination is that of a potassium-sparing, distal
      acting diuretic (eg, spironolactone) with a loop diuretic (eg, furosemide). LVP
      provides rapid resolution of symptoms with minimal complications and is well
      tolerated by most patients. Post-paracentesis circulatory dysfunction (PPCD) may
      occur after LVP and is characterized by hyponatremia, azotemia, and an increase
      in plasma renin activity. PPCD is associated with an increased mortality and may
      be prevented by administration of albumin intravenously (6 to 8 g/L of ascites
      removed) along with LVP. The development of either diuretic-resistant or diuretic
      intractable ascites occurs in approximately 5% to 10 % of all cases of ascites.
      This is a poor prognostic sign, as 50% of such patients die within 6 months of
      its development. The only definitive therapy for refractory ascites with
      cirrhosis is orthotopic liver transplantation. The other options that are
      available include LVP, peritoneovenous shunts, and transjugular intrahepatic
      portosystemic shunts (TIPS). The TIPS procedure has not been shown to have any
      influence on survival in patients with cirrhosis and refractory ascites, and TIPS
      is contraindicated in patients who have advanced liver failure because it can
      hasten death in such individuals. Peritoneovenous shunts are associated with a
      high incidence of complications and frequent occlusion. They are, therefore,
      rarely used for refractory ascites. Spontaneous bacterial peritonitis (SBP) is a
      common complication of cirrhotic ascites. It may precipitate hepatorenal
      syndrome. The overall mortality rate from an episode of SBP is approximately 20%.
      Following an episode of SBP, the 1-year mortality rate approaches 70%.
      Hospitalized patients should be treated with intravenous third-generation
      cephalosporins (eg, cefotaxime), and patients at risk should receive prophylaxis
      with either orally administered quinolones (eg, norfloxacin) or cotrimoxazole.

PMID- 14585239
TI  - Current Management of Esophageal Varices.
AB  - Acute variceal hemorrhage is the most lethal complication of cirrhosis. The
      reported mortality rate from a first episode of variceal hemorrhage is 17% to
      57%. Management of varices can be categorized into three phases: 1) prevention of
      initial bleeding, 2) management of acute bleeding, and 3) prevention of
      rebleeding. Modalities for treatment include pharmacologic, endoscopic, and shunt
      therapy. For the prevention of first variceal hemorrhage, cirrhotic patients
      should undergo endoscopy to identify patients with large varices. Priority for
      screening for varices should be given to patients with low platelet count,
      splenomegaly, and advanced cirrhosis. Once large varices are identified, patients
      should be started on beta-blocker therapy, which reduces the risk of bleeding by
      50%. If pharmacologic therapy is not tolerated or contraindicated, endoscopic
      band ligation should be performed, and surveillance of varices should be
      performed every 6 months thereafter. Shunt procedures are not indicated due to
      their higher rates of complications compared with medical therapy. For the
      management of acute variceal hemorrhage, patients should be started on
      prophylactic intravenous antibiotics and intravenous octreotide. Endoscopy should
      be performed to diagnose and treat variceal hemorrhage. Band ligation appears to
      be as effective as sclerotherapy, but with less complications. If hemostasis is
      not achieved, balloon tamponade can be used as a bridge to definitive therapy,
      which in this case would be a transjugular intrahepatic portosystemic shunt
      (TIPS). If TIPS is unavailable, a surgical shunt is indicated. Once an episode of
      acute bleeding has been controlled, variceal eradication is best accomplished
      with repeat band ligation every 10 to 14 days until varices are obliterated.
      Prevention of recurrent bleeding can be achieved with beta-blocker therapy. The
      addition of isosorbide mononitrate further reduces recurrent bleeding. This
      combination pharmacologic therapy has been shown to be superior to sclerotherapy
      and may be superior to band ligation. However, side effects of combination
      pharmacologic therapy may limit its effectiveness. Band ligation is preferred to
      sclerotherapy when considering endoscopic therapy due to less complications and
      lower cost. Surgical shunts should be used for prevention of rebleeding in
      patients who do not tolerate or are noncompliant with medical therapy and who
      have relatively preserved liver function. TIPS should be reserved for patients
      who have poor liver function and who have failed medical therapy.

PMID- 14585240
TI  - Endoscopic Management of Biliary Complications After Orthotopic Liver
      Transplantation.
AB  - After orthotopic liver transplantation (OLT), biliary duct complications can
      occur in as many as 10% to 35% of patients. In the early medical and surgical
      literature, surgical therapy was the primary mode of management of biliary tract
      complications and was the eventual course of operative intervention in up to 70%
      of cases. However, with recent advances in therapeutic biliary endoscopy, the
      current endoscopic and transplantation literature suggests that endoscopic
      management with techniques such as endoscopic retrograde cholangiopancreatography
      (ERCP) with endoscopic sphincterotomy, biliary stenting, and stone removal
      techniques can be successfully applied for the majority of post-OLT biliary
      complications. The most common biliary complications after OLT include biliary
      strictures (anastomotic and nonanastomotic); bile duct leaks, common bile duct
      stones, and biliary casts; sphincter of Oddi/ampullary muscle dysfunction/spasm;
      and disease recurrence (eg, primary sclerosing cholangitis). Predisposing factors
      for biliary complications after OLT include hepatic artery thrombosis, impaired
      perfusion of the biliary tree, portal vein thrombosis, and preservation or
      harvesting injuries, which can increase the incidence of complications as much as
      40%. Use of immunosuppressive agents such as cyclosporine can lead to
      cholesterol/bile stasis and stone formation. Outside of endoscopic therapy, there
      is little medical or dietary management that can be applied for post-OLT biliary
      complications. Ursodiol (ursodeoxycholic acid) has often been used as a
      neoadjuvant to ERCP therapy in the setting of common bile duct stones/casts, and
      low-fat diets may be recommended in this setting, but no large, randomized trials
      have advocated medical or conservative management alone.

PMID- 14585241
TI  - Treatment of Hepatitis C Virus in the Liver Transplant Recipient.
AB  - Significant necroinflammatory and/or fibrotic histologic changes should prompt
      consideration of antiviral therapy in liver transplant recipients with chronic
      hepatitis C. Depending on the patient, consideration of lower-dose pegylated
      interferon initially, with an increase to standard doses over the course of 1
      month, may improve patient compliance and tolerance. The use of growth factors to
      prevent anemia and leukopenia is encouraged. Liver transplant recipients should
      be treated for at least 1 year, until data are available on optimal duration of
      therapy in non-genotype 1 patients in this patient subpopulation.

PMID- 14585243
TI  - Brain expansion and comparative prenatal ontogeny of the non-hominoid primate
      cranial base.
AB  - The basicranium is the keystone of the primate skull, and understanding its
      morphological interdependence on surrounding soft-tissue structures, such as the
      brain, can reveal important mechanisms of skull development and evolution. In
      particular, several extensive investigations have shown that, across extant adult
      primates, the degree of basicranial flexion and petrous orientation are closely
      linked to increases in brain size relative to cranial base length. The aim of
      this study was to determine if an equivalent link exists during prenatal life.
      Specific hypotheses tested included the idea that increases in relative
      endocranial size (IRE5), relative infratentorial size (RIE), and differential
      encephalization (IDE) determine the degree of basicranial flexion and coronal
      petrous reorientation during non-hominoid primate fetal development. Cross
      sectional fetal samples of Alouatta caraya (n=17) and Macaca nemestrina (n=24)
      were imaged using high-resolution magnetic resonance imaging (hrMRI). Cranial
      base angles (CBA), petrous orientations (IPA), base lengths, and endocranial
      volumes were measured from the images. Findings for both samples showed
      retroflexion, or flattening, of the cranial base and coronal petrous
      reorientation as well as considerable increases in absolute and relative brain
      sizes. Although significant correlations of both IRE5 and RIE were observed
      against CBA and IPA, the correlation with CBA was in the opposite direction to
      that predicted by the hypotheses. Variations of IDE were not significantly
      correlated with either angle. Correlations of IPA with IRE5 and RIE appeared to
      support the hypotheses. However, partial coefficients computed for all
      significant correlations indicated that changes to the fetal non-hominoid primate
      cranial base were more closely related to increases in body size than the
      hypothesized influence of relative brain enlargement. These findings were
      discussed together with those from a previous study of modern human fetuses.

PMID- 14585244
TI  - Ontogeny and phylogeny in papionin primates.
AB  - This study investigates the developmental bases of size and shape variation in
      papionin primates (Macaca, Cercocebus, Mandrillus, Lophocebus, and Papio). The
      analysis tests hypotheses predicting that heterochronic changes in ontogeny,
      particularly in the degree of overall size growth, can account for cranial
      diversity and "allometric scaling" in this clade. Large developmental samples of
      extant papionin crania are examined to test heterochronic hypotheses using
      bivariate allometric methods. Analyses indicate that the crania of larger
      papionins (Mandrillus and Papio) are generally peramorphic, surpassing size and
      shape ranges of smaller, and probably less-derived, macaques and mangabeys. At
      least two heterochronic processes, including acceleration and hypermorphosis, can
      account for this pattern. Ontogenetic changes include decoupling of growth and
      development among cranial regions, along with simple shifts in size. Allometric
      scaling has complex developmental bases. Size change itself is not sufficient to
      explain all developmental differences among papionins, but these changes are
      extremely important in comparisons within cranial regions such as the face.
      Results imply that Papio exhibits strongly derived patterns of brain growth that
      impact postnatal patterns of size and shape transformation. Consideration of
      these results in the context of recent socioecological analyses suggests that
      derived patterns of cranial growth in Papio may be a response to selection during
      the early periods of ontogeny, resulting in a distinctive life history pattern.

PMID- 14585245
TI  - Ontogenetic adaptation to bipedalism: age changes in femoral to humeral length
      and strength proportions in humans, with a comparison to baboons.
AB  - The increase in lower/upper limb bone length and strength proportions in adult
      humans compared to most other anthropoid primates is commonly viewed as an
      adaptation to bipedalism. The ontogenetic development of femoral to humeral
      proportions is examined here using a longitudinal sample of 20 individuals
      measured radiographically at semiannual or annual intervals from 6 months of age
      to late adolescence (a subset of the Denver Growth Study sample). Anthropometric
      data (body weights, muscle breadths) were also available at each examination age.
      Results show that while femoral/humeral length proportions close to those of
      adults are already present in human infants, characteristically human
      femoral/humeral diaphyseal strength proportions only develop after the adoption
      of bipedalism at about 1 year of age. A rapid increase in femoral/humeral
      strength occurs between 1 and 3 years, followed by a slow increase until mid-late
      adolescence, when adult proportions are reached. When age changes in material
      properties are factored in, femoral strength shows an almost constant
      relationship to body size (body mass.bone length) after 5 years of age, while
      humeral strength shows a progressive decline relative to body size.
      Femoral/humeral length proportions increase slightly throughout growth, with no
      apparent change in growth trajectory at the initiation of walking, and with a
      small decline in late adolescence due to later growth in length of the humerus. A
      sex difference in femoral/humeral strength proportions (females greater) but not
      length proportions, develops early in childhood. Thus, growth trajectories in
      length and strength proportions are largely independent, with strength
      proportions more responsive to actual changes in mechanical loading. A cross
      sectional ontogenetic sample of baboons (n=30) illustrates contrasting patterns
      of growth, with much smaller age changes in proportions, particularly strength
      proportions, although there is some indication of an adaptation to altered limb
      loadings early in baboon development.

PMID- 14585246
TI  - Global risk assessment for cardiovascular disease and astute clinical judgement.

PMID- 14585247
TI  - When the endothelium cannot say 'NO' anymore. ADMA, an endogenous inhibitor of NO
      synthase, promotes cardiovascular disease.

PMID- 14585248
TI  - Are the Framingham and PROCAM coronary heart disease risk functions applicable to
      different European populations? The PRIME Study.
AB  - AIMS: To assess whether the Framingham and PROCAM risk functions were applicable
      to men in Belfast and France. METHODS AND RESULTS: We performed an external
      validation study within the PRIME (Prospective Epidemiological Study of
      Myocardial Infarction) cohort study. It comprised men recruited in Belfast (2399)
      and France (7359) who were aged 50 to 59 years, free of CHD at baseline (1991 to
      1993) and followed over 5 years for CHD events (coronary death, myocardial
      infarction, angina pectoris). We compared the relative risks of CHD associated
      with the classic risk factors in PRIME with those in Framingham and PROCAM
      cohorts. We then compared the number of predicted and observed 5-year CHD events
      (calibration). Finally, we estimated the ability of the risk functions to
      separate high risk from low risk subjects (discrimination). The relative risk of
      CHD calculated for the various factors in the PRIME population were not
      statistically different from those published in the Framingham and PROCAM risk
      functions. The number of CHD events predicted by these risk functions however
      clearly overestimated those observed in Belfast and France. The two risk
      functions had a similar ability to separate high risk from low risk subjects in
      Belfast and France (c-statistic range: 0.61-0.68). CONCLUSION: The Framingham and
      PROCAM risk functions should not be used to estimate the absolute CHD risk of
      middle-aged men in Belfast and France without any CHD history because of a clear
      overestimation. Specific population risk functions are needed.

PMID- 14585249
TI  - Plasma levels of asymmetrical dimethylarginine and adverse cardiovascular events
      after percutaneous coronary intervention.
AB  - AIMS: We investigated the predictive value of plasma concentration of
      asymmetrical dimethylarginine (ADMA) on clinical outcome in patients undergoing
      percutaneous coronary intervention (PCI). METHODS AND RESULTS: One-hundred and
      fifty-three consecutive patients with stable angina and undergoing PCI were
      prospectively enrolled for clinical follow-up. Plasma ADMA levels were determined
      before procedure by high performance liquid chromatography. The major adverse
      cardiovascular events included cardiovascular death, myocardial infarction, and
      repeat revascularization of target vessels. Patients were grouped into tertiles
      according to their plasma ADMA levels. Over a follow-up period of 16 months
      (median), cardiovascular events occurred in 6 patients of tertile I
      (<0.50microM), in 17 patients of tertile II (0.50-0.62microM), and in 28 patients
      of tertile III (>0.62microM), P<0.001. By multivariate analysis, tertiles of ADMA
      levels were independently associated with a higher risk of adverse cardiovascular
      events after PCI (relative risk: tertile II vs I: 3.0 [1.2-7.7], P=0.022; tertile
      III vs I: 5.3 [2.2-12.9], P<0.001). Moreover, plasma ADMA level in the highest
      tertile also appeared as a significant risk factor of subsequent death and non
      fatal myocardial infarction after PCI (tertile III vs I, P=0.04). CONCLUSION: Pre
      procedural plasma ADMA levels may independently predict subsequent adverse
      cardiovascular events in patients undergoing PCI. Measurement of plasma ADMA
      levels could provide a rationale for risk stratification of patients by measuring
      ADMA levels before intervention.

PMID- 14585250
TI  - The Extensive Lifestyle Management Intervention (ELMI) following cardiac
      rehabilitation trial.
AB  - AIM: Previous studies have reported lifestyle and risk factor deterioration
      following completion of a cardiac rehabilitation program (CRP). We report the
      results of a one-year Extensive Lifestyle Management Intervention (ELMI) aimed at
      preventing these adverse changes. METHODS AND RESULTS: A total of 302 men and
      women with ischaemic heart disease were recruited following completion of a CRP
      and randomized to either the ELMI (consisting of exercise sessions, telephone
      follow-ups and risk factor and lifestyle counselling) or usual care. The primary
      outcome was global cardiovascular risk using the Framingham and Procam risk
      scores. Secondary outcomes included risk factors and lifestyle behaviours.
      Baseline characteristics were similar between the two groups. Adherence to the
      ELMI was high. There was a non-significant trend in favour of the ELMI between
      for both the Framingham (6.6+/-3.1 to 6.2+/-2.9 vs 6.6+/-3.2 to 6.7+/-3.2,
      P=0.138) and Procam (20.0+/-20.0 to 20.6+/-19.5 vs 19.1+/-18.7 to 21.8+/-19.1,
      P=0.089) scores. There were no differences in secondary outcomes. CONCLUSIONS: A
      one-year multi-factorial post-CRP intervention results in modest, non-significant
      benefits to global risk compared to usual care. The absence of deterioration in
      the usual care group may be due to improved practices in usual care.

PMID- 14585251
TI  - Report of erectile dysfunction after therapy with beta-blockers is related to
      patient knowledge of side effects and is reversed by placebo.
AB  - AIMS: Patients with cardiovascular diseases frequently complain of erectile
      dysfunction especially when treated with beta-blockers. In order to assess
      whether the effect of beta-blockers on erectile dysfunction is in part related to
      patient knowledge of the drug side effects, 96 patients (all males, age 52+/-7
      years) with newly diagnosed cardiovascular disease and not suffering from
      erectile dysfunction entered a two phase, single cross over study. METHODS AND
      RESULTS: During the first phase of the study patients received atenolol 50mg o.d.
      (A), 32 patients were blinded on the drug given (group A), 32 were informed on
      the drug given but not on its side effects (group B) and 32 took A after being
      informed on its side effects on erectile function (group C). After 3 months the
      incidence of erectile dysfunction was 3.1% in the group A, 15.6% in group B and
      31.2% in group C (P<0.01). All patients reporting ED entered the second phase of
      the study and were randomised to receive Sildenafil 50mg and placebo in a cross
      over study. Sildenafil citrate and placebo were equally effective in reversing
      erectile dysfunction in all but one patient reporting ED with Atenolol.
      CONCLUSION: Our results show that the knowledge and prejudice about side effects
      of beta-blockers can produce anxiety, that may cause erectile function.

PMID- 14585252
TI  - Impact of body mass index on outcome in patients after coronary artery bypass
      grafting with and without valve surgery.
AB  - BACKGROUND: Among other preoperative parameters, extremely low or extremely high
      body mass index (BMI) has been discussed as a substantial risk factor for
      postoperative complications after cardiac surgery. However, the exact
      relationship between BMI and postoperative risk has not yet been defined.
      METHODS: We retrospectively investigated consecutive patients (n=22666) who
      underwent coronary artery bypass grafting with or without concomitant valve
      surgery between 1990 and 2001 in our institution. A number of preoperative and
      intraoperative variables and BMI (as a quadratic term) were used in a logistic
      regression model as covariates. Further, the patients were divided into 20 groups
      each with an increase in BMI of 1kg/m(2)(BMI as a categorical variable). The
      calculations of odds ratios (ORs) for re-intubation, infection, re-exploration,
      prolonged stay (>1 day) on the intensive care unit (ICU) and 30-day mortality
      were adjusted for age, gender and type of surgery. RESULTS: In the multivariate
      analysis only age (OR between 1.01 and 1.038, P<0.01), additional aortic valve
      (OR between 1.335 and 2.977, P<0.01) or mitral valve surgery (OR between 2.123
      and 3.301, P<0.01) showed significant impact on all five end-points. Patients
      with BMI between 25 and 35kg/m(2)were not at elevated risk for any of the
      investigated end-points, except for infection. Patients with BMI between 21 and
      27kg/m(2)were not at elevated risk for infection. The ORs for postoperative
      complications were significantly higher in underweight patients compared with
      obese or severely obese patients, except those for infection. Further, the
      underweight patients presented significantly more comorbidity. CONCLUSION:
      Patients with low BMI are at higher risk after cardiac surgery than obese or
      severely obese patients. We hypothesize that a preoperative focus on avoiding
      and/or reversing cachexia may be more efficacious than reducing obesity in
      reducing the overall risk associated with heart surgery.

PMID- 14585254
TI  - Impact of Closed-Loop Stimulation, overdrive pacing, DDDR pacing mode on atrial
      tachyarrhythmia burden in Brady-Tachy Syndrome. A randomized study.
AB  - AIMS: Atrial overdrive pacing algorithms increase Atrial Pacing Percentage (APP)
      to reduce Atrial Tachyarrhythmia (AT) recurrences in patients with Brady-Tachy
      Syndrome (BTS). This study aimed to compare AT burden and APP in BTS patients
      treated with conventional DDDR pacing, DDD+ overdrive or Closed-Loop Stimulation
      (CLS). METHODS AND RESULTS: One hundred and forty-nine BTS patients were included
      (72 male, mean age 74+/-9), who received a dual chamber pacemaker (Philos DR or
      Inos 2+CLS, Biotronik GmbH, Berlin, Germany) programmed in DDD at 70min(-1). At 1
      month follow-up, DDDR, DDD+ or CLS algorithms were activated according to
      randomization. Follow-up visits for data collection were performed at 4 and 7
      months. Non parametric statistical tests (Kruskal-Wallis H-test, Dunn test,
      Spearman coefficient) were used to analyse not-normally-distributed samples. At 7
      months, AT burden was significantly lower in CLS group (20.3+/-63.1min/day,
      P<0.01) compared to DDDR (56.0+/-184.0min/day) and DDD+ group (63.1+/
      113.8min/day). APP was higher in CLS (89.0+/-13.2%) and in DDD+ group (97.9+/
      2.7%) than in DDDR group (71.1+/-26.7%, P<0.001). The correlation found between
      AT burden and APP was very weak: at 7-month follow-up the Spearman coefficient
      was -0.29 (P=NS) in CLS, -0.52 (P<0.01) in DDD+, -0.22 (P=NS) in DDDR.
      CONCLUSIONS: CLS pacing was associated with a significantly lower AT
      burden,compared to the other pacing algorithms. Moreover APP was significantly
      higher in DDD+ and in CLS mode, than in DDDR. APP weakly correlated with AT
      burden only in DDD+ mode, though the lowest AT burden level was obtained in the
      CLS group where no significant correlation was found.

PMID- 14585253
TI  - Atrial structural remodelling and restoration of atrial contraction after linear
      ablation for atrial fibrillation.
AB  - AIMS: We determined late atrial function following a surgical linear endocardial
      radiofrequency (RF) ablation procedure that aimed to restore and maintain sinus
      rhythm (SR) in atrial fibrillation (AF). We tested the hypothesis that successful
      restoration of SR is accompanied by measurable mechanical atrial function that is
      at normal or near normal levels. METHODS: Forty-seven patients who underwent the
      surgical RF procedure at least 6 months previously (median 2.86 years; range: 0.6
      4.2 years) were studied using an array of echocardiographic variables. Two
      patient groups (SR restored [RF-SR], persistent AF [RF-AF]) and an age matched
      control group were studied. Among the echocardiographic variables measured were
      left atrial (LA) size and volume, LA active fractional emptying and mitral
      annular displacement corresponding to atrial contraction (A' velocity) by Doppler
      tissue imaging. RESULTS: At long term follow up 29/47of patients who underwent
      the RF procedure were in SR with atrial contraction present
      echocardiographically. Of the patients initially restored to SR, the proportion
      remaining in SR at 3 years was 79% (SE 9%). The atrial-emptying fraction was
      reduced in comparison to that seen in normal controls (27+/-14% vs 46+/-10%). The
      A' velocity was decreased in the surgical RF cohort vs controls (4.4+/-1.3 vs
      9.7+/-1.7cm/s; P=0.0001). Despite LA size preoperatively being similar in both
      surgical groups, atrial size decreased in those in whom SR was restored (48.6+/
      7.6 vs 44.8+/-4.7mm; P=0.0001) but increased in those in whom AF persisted
      (48.2+/-8.1mm vs 52.3+/-7.8mm; P=0.0001). CONCLUSION: The radial pattern of
      linear radiofrequency ablation used in the present study resulted in restoration
      of SR and atrial function. Procedural success was independent of preoperative
      atrial size. Restoration of SR results in 'reverse' atrial remodelling and
      improved atrial function. However atrial function remains modestly impaired,
      either due to the ablation lesions or pre-existing atrial disease.

PMID- 14585255
TI  - Medical Practice Guidelines. Separating science from economics.

PMID- 14585256
TI  - American College of Cardiology/European Society of Cardiology Clinical Expert
      Consensus Document on Hypertrophic Cardiomyopathy. A report of the American
      College of Cardiology Foundation Task Force on Clinical Expert Consensus
      Documents and the European Society of Cardiology Committee for Practice
      Guidelines.

PMID- 14585257
TI  - Hereditary nonpolyposis colorectal cancer: preventive management.
AB  - Hereditary nonpolyposis colorectal cancer (HNPCC) is the most common form of
      hereditary colorectal cancer. Inherited mutations in the mismatch repair genes
      associated with this syndrome have an approximate 80% lifetime risk of colorectal
      cancer. Since there are no premonitory signs of susceptibility to HNPCC, family
      history is the initial method for identifying those at increased risk. At risk
      individuals should undergo genetic counseling and testing. Although an
      algorithmic indication for genetic testing in at risk HNPCC patients is yet to be
      determined, many advocate initial screening for microsatellite instability (MSI)
      of the cancer specimen in individuals suspected of carrying HNPCC mutations.
      Those who test positive for MSI can then undergo further testing for mutations in
      the associated germline mismatch repair genes. Techniques for detecting these
      mutations currently include in vitro synthesized-protein assay, single-strand
      conformational polymorphism, and DNA sequencing. Given the aggressive nature of
      HNPCC adenomas, individuals who test positive for HNPCC mutations are recommended
      to undergo yearly colonoscopic surveillance starting at the age of 25. A
      reasonable alternative to lifetime colonoscopic surveillance for the prevention
      of colorectal cancer in these individuals is prophylactic colectomy. The
      prevention of colorectal cancer through pharmacological means is under
      investigation as another option in the management of HNPCC patients.
      Specifically, chemoprevention trials are currently ongoing to evaluate the
      efficacy of COX-2 inhibitors in the prevention of colorectal cancer in HNPCC and
      familial adenomatous polyposis patients.

PMID- 14585258
TI  - Acute and long-term toxicity following radiotherapy alone or in combination with
      chemotherapy for locally advanced cervical cancer.
AB  - Randomised studies in locally advanced cervical cancer patients showed that
      cisplatin should be given concurrently with radiotherapy, because of a better
      long-term survival compared to radiotherapy alone. This increases the relevance
      of treatment related toxicity. This review summarises the acute and long-term
      toxicity of radiotherapy given with or without chemotherapy for cervical cancer.
      Acute toxicity (all grades) of radiotherapy is reported in 61% of the patients in
      the rectosigmoid, in 27% as urological, in 27% as skin and in 20% as
      gynaecological toxicity. Moderate and severe morbidity consists of 5% to 7%
      gastrointestinal and 1% to 4% genitourinary toxicity. Adding chemotherapy to
      radiotherapy increases acute haematological toxicity to 5% to 37% of the patients
      and nausea and vomiting in 12% to 14%. Late effects of radiotherapy include
      gastrointestinal, urological, female reproductive tract, skeletal and vascular
      toxicity, secondary malignancies and quality of life issues. For at least 20
      years after treatment, new side effects may develop. Gastrointestinal toxicity
      usually occurs in the first 2 years after treatment in about 10% of the patients.
      The incidence of moderate and severe urological toxicity can increase up to 10%
      and rises over time. Gynaecological toxicity usually occurs shortly after
      treatment while skeletal and vascular toxicity can occur years to decades later.
      Thus far, no increase in late toxicity has been observed after the addition of
      cisplatin to radiotherapy. Finally, methods to prevent or decrease late toxicity
      and therapeutical options are discussed. However, most randomised studies still
      have a limited follow-up period.

PMID- 14585259
TI  - Methionine dependency and cancer treatment.
AB  - Conventional chemotherapies have showed their limits, notably for patients with
      advanced cancer. New therapeutic strategies must be identified, and the metabolic
      abnormalities of cancer cells offer such opportunities. Many human cancer cell
      lines and primary tumors have absolute requirements for methionine, an essential
      amino acid. In contrast, normal cells are relatively resistant to exogenous
      methionine restriction. The biochemical mechanism for methionine dependency has
      been studied extensively, but the fundamental mechanism remains unclear. A number
      of investigators have attempted to exploit the methionine dependence of tumors
      for therapeutic effects in vivo. To reduce in vivo methionine in plasma and
      tumours, dietary and pharmacological treatments have been used. Methionine-free
      diet or methionine-deprived total parenteral nutrition causes regression of a
      variety of animal tumours. Alternatively, methionine depletion was achieved by
      the use of methioninase. This enzyme specifically degrades methionine and
      inhibits tumour growth in preclinical models. Because of potential toxicity and
      quality of life problems, prolonged methionine restriction with diet or with
      methioninase is not suitable for clinical use. Methionine restriction may find
      greater application in association with various chemotherapeutic agents. Several
      preclinical studies have demonstrated synergy between methionine restriction and
      various cytotoxic chemotherapy drugs. The experimental results accumulated during
      the last three decades suggest that methionine restriction can become an
      additional cancer therapeutic strategy, notably in association with chemotherapy.

PMID- 14585260
TI  - Prevention of chemotherapy and radiation toxicity with glutamine.
AB  - GOALS OF THE WORK: Malignancy produces a state of physiologic stress that is
      characterized by a relative deficiency of glutamine, a condition that is further
      exacerbated by the effects of cancer treatment. Glutamine deficiency may impact
      on normal tissue tolerance to antitumor treatment, and may lead to dose
      reductions and compromised treatment outcome. Providing supplemental glutamine
      during cancer treatment has the potential to abrogate treatment-related toxicity.
      We reviewed the available data on the use of glutamine to decrease the incidence
      and severity of adverse effects due to chemotherapy and/or radiation in cancer
      patients. METHODS: We performed a search of the MEDLINE database during the time
      period 1980-2003, and reviewed the English language literature of both human and
      animal studies pertaining to the use of glutamine in subjects with cancer. We
      also manually searched the bibliographies of published articles for relevant
      references. MAIN RESULTS: The available evidence suggests that glutamine
      supplementation may decrease the incidence and/or severity of chemotherapy
      associated mucositis, irinotecan-associated diarrhea, paclitaxel-induced
      neuropathy, hepatic veno-occlusive disease in the setting of high dose
      chemotherapy and stem cell transplantation, and the cardiotoxicity that
      accompanies anthracycline use. Oral glutamine supplementation may enhance the
      therapeutic index by protecting normal tissues from, and sensitizing tumor cells
      to chemotherapy and radiation-related injury. CONCLUSIONS: The role of glutamine
      in the prevention of chemotherapy and radiation-induced toxicity is evolving.
      Glutamine supplementation is inexpensive and it may reduce the incidence of
      gastrointestinal, neurologic, and possibly cardiac complications of cancer
      therapy. Further studies, particularly placebo-controlled phase III trials, are
      needed to define its role in chemotherapy-induced toxicity.

PMID- 14585261
TI  - Classification of anticancer drugs--a new system based on therapeutic targets.
AB  - The arrival of a great number of new antineoplastic agents has made it necessary
      to reclassify all of them. Anticancer drugs may act at different levels: cancer
      cells, endothelium, extracellular matrix, the immune system or host cells. The
      tumour cell can be targeted at the DNA, RNA or protein level. Most classical
      chemotherapeutic agents interact with tumour DNA, whereas monoclonal antibodies
      and small molecules are directed against proteins. The endothelium and
      extracellular matrix may be affected also by specific antibodies and small
      molecules.

PMID- 14585262
TI  - Oesophageal cancer: new developments in systemic therapy.
AB  - Oesophageal cancer is a rare but highly virulent malignancy in the United States
      and Western countries, and adenocarcinoma of the oesophagus has had the most
      rapid rate of increase of any solid tumour malignancy. Systemic metastatic
      disease is present in 50% of patients at diagnosis, and in the remaining 50% of
      patients presenting initially with loco-regional disease, systemic metastatic
      disease will develop in the vast majority of these patients. Combined
      chemotherapy and radiotherapy is the standard of care in the nonsurgical
      management of oesophageal cancer. Preoperative chemoradiotherapy followed by
      surgery continues to be actively studied in the surgical management of locally
      advanced oesophageal cancer. Pathologic complete responses are seen in 20-40% of
      patients, with five-year survival achieved in 25-35% of patients. The limited
      efficacy and substantial toxicity of conventional 5-FU-cisplatin-based
      chemotherapy combined with radiation, or used to treat advanced disease, has
      prompted the evaluation of newer agents, including the taxanes and irinotecan.
      These trials have indicated promising antitumour activity and therapy tolerance
      in both advanced disease and in combined modality therapy trials, depending on
      the dose and schedule of therapy administered. The advent of newer, targeted
      therapies, including agents directed against growth factor receptor pathways,
      tumour angiogenesis, and tumour invasion and metastasis, is leading to a new
      generation of clinical trials combining these agents with conventional cytotoxic
      chemotherapy and radiation.

PMID- 14585263
TI  - The management of brain metastases.
AB  - Brain metastases are neoplasms that originate in tissues outside the brain and
      then spread secondarily to the brain. Metastases to the brain are the most common
      intracranial tumours in adults. Substantial progress has been made in the
      treatment of these tumours, and radiotherapy, surgery, and stereotactic
      radiosurgery are now established treatments. With aggressive treatment, most
      patients experience meaningful symptom reduction and extension of life.

PMID- 14585265
TI  - Oral antibiotic administration and early hospital discharge is a safe and
      effective alternative for treatment of low-risk neutropenic fever.

PMID- 14585264
TI  - Cellular pH regulators: potentially promising molecular targets for cancer
      chemotherapy.
AB  - One of the major obstacles to the successful treatment of cancer is the complex
      biology of solid tumour development. Although regulation of intracellular pH has
      been shown to be critically important for many cellular functions, pH regulation
      has not been fully investigated in the field of cancer. It has, however, been
      shown that cellular pH is crucial for biological functions such as cell
      proliferation, invasion and metastasis, drug resistance and apoptosis. Hypoxic
      conditions are often observed during the development of solid tumours and lead to
      intracellular and extracellular acidosis. Cellular acidosis has been shown to be
      a trigger in the early phase of apoptosis and leads to activation of
      endonucleases inducing DNA fragmentation. To avoid intracellular acidification
      under such conditions, pH regulators are thought to be up-regulated in tumour
      cells. Four major types of pH regulator have been identified: the proton pump,
      the sodium-proton exchanger family (NHE), the bicarbonate transporter family
      (BCT) and the monocarboxylate transporter family (MCT). Here, we describe the
      structure and function of pH regulators expressed in tumour tissue. Understanding
      pH regulation in tumour cells may provide new ways of inducing tumour-specific
      apoptosis, thus aiding cancer chemotherapy.

PMID- 14585266
TI  - High dose therapy and autologous stem cell transplant does not improve survival
      compared with continued combination chemotherapy in people at high risk of
      relapse after initial treatment of advanced Hodgkin's lymphoma.

PMID- 14585267
TI  - Mitomycin C provides little additional benefit in the treatment of carcinoma of
      unknown primary site.

PMID- 14585270
TI  - DNA methylation in the immune system.

PMID- 14585268
TI  - Adding interferon-alpha to octreotide slows tumour progression compared with
      octreotide alone but evidence is lacking for improved survival in people with
      disseminated midgut carcinoid tumours.

PMID- 14585271
TI  - Mammalian DNA (cytosine-5) methyltransferases and their expression.
AB  - Two classes of functional DNA (cytosine-5) methyltransferases have been
      discovered in mammals to date. One class methylates the unmodified DNA and is
      designated as the de novo enzyme, whereas the other maintains the methylation
      status of the daughter strand during DNA replication and thus is referred to as a
      maintenance DNA methyltransferase. Each enzyme catalyzes methyl group transfer
      from S-adenosyl-L-methionine to cytosine bases in DNA. During methylation the
      enzyme flips its target base out of the DNA duplex into a typically concave
      catalytic pocket. This flipped cytosine base is then a substrate for the enzyme
      catalyzed reaction. The newly formed 5-methylcytosine confers epigenetic
      information on the parental genome without altering nucleotide sequences. This
      epigenetic information is inherited during DNA replication and cell division. In
      mammals, DNA methylation participates in gene expression, protection of the
      genome against selfish DNA, parental imprinting, mammalian X chromosome
      inactivation, developmental regulation, T cell development, and various diseases.

PMID- 14585272
TI  - The ICF syndrome, a DNA methyltransferase 3B deficiency and immunodeficiency
      disease.
AB  - Only one human disease that involves Mendelian inheritance of immunodeficiency
      and aberrant DNA methylation has been identified. This is a rare chromosome
      breakage disease called the immunodeficiency, centromeric region instability, and
      facial anomalies syndrome (ICF). Its diagnostic characteristics are
      agammaglobulinemia with B cells as well as DNA rearrangements targeted to the
      centromere-adjacent heterochromatic region (qh) of chromosomes 1, 16, and
      sometimes 9 in mitogen-stimulated lymphocytes. These rearrangement-prone regions
      show DNA hypomethylation in all examined ICF cell populations. This review
      summarizes our knowledge about the immunological symptoms of ICF; the nature of
      DNMT3B mutations in ICF patients; the phenotypes of DNA hypomethylation mutants
      in humans, mice, and Arabidopsis; the epigenetics of ICF; and ICF-specific RNA
      expression and cell-surface antigen expression in lymphoblastoid cell lines.
      Comparisons of ICF and control lymphoblastoid cell lines and ICF patients'
      symptoms suggest an involvement of DNA methylation in the late stages of
      lymphocyte maturation.

PMID- 14585273
TI  - Epigenetic regulation of antigen receptor rearrangement.
AB  - In the mammalian immune system, V(D)J rearrangement of immunoglobulin (Ig) and T
      cell receptor (TCR) genes is regulated in a lineage- and stage-specific fashion.
      Because each of the seven loci capable of rearrangement utilizes the same
      recombination machinery, it is thought that V(D)J recombination of each antigen
      receptor locus is regulated through the differential accessibility of each locus
      to the V(D)J recombination machinery. Accumulating evidence indicates that
      chromatin remodeling mediated by DNA methylation and demethylation plays
      important roles in regulating V(D)J recombination and germline transcription
      through the Ig and TCR loci. DNA demethylation within the antigen receptor loci
      appears to be regulated by cis-elements also required for coordinated V(D)J
      recombination and germline transcription. In this paper, we critically examine
      the relationship between demethylation and V(D)J recombination as well as the
      mechanism to regulate DNA demethylation within the antigen receptor loci.

PMID- 14585274
TI  - Methylation and demethylation in the regulation of genes, cells, and responses in
      the immune system.
AB  - DNA methylation is a focus of epigenetic research in the immune system. This
      overview begins with a synopsis of the players and processes involved in DNA
      methylation, demethylation, methyl-CpG-recognition, histone modification, and
      chromatin remodeling. The role of these mechanisms in immune responses, with a
      focus on T lymphocytes, is then reviewed. There is evidence for epigenetic
      regulation of several key immune processes including thymocyte development,
      antigen presentation, differentiation, cytokine expression, effector function,
      and memory. DNA methylation contributes, along with other epigenetic mechanisms,
      to the establishment of transcriptional thresholds that vary between genes and T
      cell types. The immune system is a fertile field for studies of epigenetic
      regulation of cell fate and function.

PMID- 14585275
TI  - DNA methylation and expression of major histocompatibility complex class I and
      class II transactivator genes in human developmental tumor cells and in T cell
      malignancies.
AB  - Major histocompatibility complex (MHC) class I and class II molecules play
      essential roles in the immune response by virtue of their ability to present
      peptides to T lymphocytes. Given their central role in adaptive immunity, the
      genes encoding these peptide-presenting molecules are regulated in a tight
      fashion to meet with local requirements for an adequate immune response. In
      contrast to MHC class I gene products, which are expressed on almost all
      nucleated cells, constitutive expression of MHC class II molecules is found in
      specialized antigen presenting cells of the immune system only. Transcription of
      both MHC class I and class II genes can be induced by immune regulators and upon
      cell activation. Transcription of MHC class I genes is mediated by a set of
      conserved cis acting regulatory elements in their promoters. Of these regulatory
      elements, MHC class II promoters share the SXY-module. Essential for activation
      of MHC class II promoters is the class II transactivator (CIITA), which acts
      through protein/protein interactions with regulatory factors bound to the SXY
      module. In this review, we discuss the role of DNA methylation in relation to
      altered expression of MHC class I and CIITA genes as observed in malignancies and
      in development.

PMID- 14585276
TI  - Stealth technology: how Epstein-Barr virus utilizes DNA methylation to cloak
      itself from immune detection.
AB  - Epstein-Barr virus (EBV) is a large lymphotrophic DNA virus that establishes life
      long residency in the infected host and is associated with a number of human
      tumors. The EBV genome encodes proteins essential for persistence, an
      oncoprotein, and proteins that render it vulnerable to the host's immune system;
      therefore, EBV gene transcription is tightly regulated. One critically important
      regulatory mechanism utilized by EBV is DNA methylation. Methylation of cytosines
      within CpG dinucleotides at promoter regions is important for gene silencing and
      genome integrity. Although most parasitic elements are methylated in mammalian
      cells never to be reactivated again, EBV has evolved to utilize DNA methylation
      to maximize persistence and cloak itself from immune detection. EBV's reliance on
      DNA methylation also provides a unique therapeutic strategy for the treatment of
      EBV-associated tumors. DNA demethylating agents are capable of reactivating
      transcription of highly immunogenic viral proteins, rendering tumor cells
      susceptible to killing by the host immune system, and inducing the viral lytic
      cycle which culminates in cell lysis.

PMID- 14585277
TI  - Immunoregulatory activity of CpG oligonucleotides in humans and nonhuman
      primates.
AB  - Oligodeoxynucleotides (ODN) containing CpG motifs mimic the ability of microbial
      DNA to activate the innate immune system. The resultant response limits the early
      spread of infectious organisms while promoting the development of adaptive
      immunity. CpG ODN show promise as vaccine adjuvants and in the treatment of
      asthma, allergy, infection, and cancer. Due to evolutionary divergence in CpG
      recognition between species, CpG ODN that are most active in rodents are poorly
      immunostimulatory in primates. Thus, evidence that CpG ODN have therapeutic
      activity in mice must be confirmed in primates. Two distinct types of CpG ODN
      were identified that stimulate primate PBMC. D-type ODN trigger plasmacytoid DC
      to secrete IFNalpha, monocytes to mature into functionally active DC, and NK
      cells to secrete IFNgamma. K-type ODN stimulate B cells and monocytes to
      proliferate and secrete IgM, IL-10, and/or IL-6. In vivo studies in nonhuman
      primates indicate that proinflammatory or humoral immune responses can be
      selectively facilitated by judicious use of these distinct types of ODN.

PMID- 14585278
TI  - DNA methylation and autoimmune disease.
AB  - DNA methylation plays an essential role in maintaining T-cell function. A growing
      body of literature indicates that failure to maintain DNA methylation levels and
      patterns in mature T cells can result in T-cell autoreactivity in vitro and
      autoimmunity in vivo. Defective maintenance of DNA methylation may be caused by
      drugs such as procainamide or hydralazine, or failure to activate the genes
      encoding maintenance DNA methyltransferases during mitosis, resulting in the
      development of a lupus-like disease or perhaps other autoimmune disorders. This
      paper reviews the evidence supporting a role for abnormal T-cell DNA methylation
      in causing autoimmunity in an animal model of drug-induced lupus, and discusses
      some of the mechanisms involved. T cells from patients with active lupus have
      evidence for most if not all of the same methylation abnormalities, suggesting
      that abnormal DNA methylation plays a role in idiopathic human lupus as well.

PMID- 14585279
TI  - Profiling aberrant DNA methylation in hematologic neoplasms: a view from the tip
      of the iceberg.
AB  - Cancer is also an epigenetic disease. The main epigenetic modification in humans
      is DNA methylation. Transformed cells undergo a dramatic change in their DNA
      methylation patterns: certain CpG islands located in the promoter regions of
      tumor-suppressor genes become hypermethylated and the contiguous gene rests
      silenced and this phenomenon occurs in an overall genomic environment of DNA
      hypomethylation. The profile of CpG island hypermethylation in hematologic
      malignancies is an epigenetic signature unique for each subtype of leukemia or
      lymphoma. Although the most widely studied genes are the cell-cycle inhibitors
      p15INK4b and p16INK4a (specially in AML and ALL), the list of methylation
      repressed genes in these neoplasms is expanding very rapidly, including MGMT,
      RARB2, CRBP1, SOCS-1, CDH1, DAPK1, and others. A necessary cross-talk between
      genetic alterations and DNA methylation exists: certain chromosomal
      translocations may induce hypermethylation, such as the PML-RARa, or attract
      methylation, such as BCR-ABL, but DNA hypomethylation can be the culprit behind
      the genesis of certain abnormal recombination events. From a translational
      standpoint, hypermethylation can be used as a marker of recurrent disease or
      progression, for example, in MDS, or response to chemotherapy, such as MGMT
      methylation in B-cell non-Hodgkin's lymphoma. Furthermore, promising studies
      using DNA demethylating agents and histone deacetylase inhibitors are underway to
      awake these dormant tumor-suppressor genes for a better treatment of the patient
      with a hematologic malignancy.

PMID- 14585280
TI  - Inhibitors of DNA methylation in the treatment of hematological malignancies and
      MDS.
AB  - DNA methylation abnormalities have recently emerged as one of the most frequent
      molecular changes in hematopoietic neoplasms. Since methylation and
      transcriptional status are inversely correlated, the hypermethylation of genes
      involved in cell-cycle control and apoptosis could have a pathogenetic role in
      the development of cancer. In particular, high-risk myelodysplastic syndromes
      (MDS) and secondary leukemias show a high prevalence of tumor suppressor gene
      hypermethylation. The progression of chronic myeloproliferative diseases and of
      myelodysplastic syndromes, as well as that of lymphoproliferative diseases, is
      associated with an increased methylation rate, pointing to a role for
      hypermethylation of critical promoter regions in the transformation to more
      aggressive phenotypes. In the same line, a significantly worse prognosis has been
      shown for patients with hypermethylation of several genes compared to that of
      patients with unmethylated genes. For these reasons, the use of irreversible DNA
      methyltransferase inhibitors, such as 5-azacytidine and Decitabine, appears to be
      a promising option for the treatment of MDS and acute myeloid leukemia. In
      clinical trials, Azacytidine results in a significantly higher response rate,
      improved quality of life, reduced risk of leukemic transformation, and improved
      survival compared to supportive care. Similarly, Decitabine showed favorable
      results, promising response rates, a good nonhematologic toxicity profile, and a
      trend for better survival compared to intensive chemotherapy, particularly in
      older patients. The synergistic effect of histone deacetylase inhibitors,
      including phenylbutyrate (PB), in reactivating silenced genes encouraged clinical
      studies on the combination of PB and demethylating agents in hematological
      diseases, characterized by p15 silencing. The sequential administration of a
      "first generation" demethylating agent and HDAC inhibitors gave preliminary
      evidence of a reduced methylation of target genes, as also described with
      Decitabine. Clinical trials are still ongoing, and preliminary data indicate for
      the first time that the natural history of MDS may be changed by a non-intensive
      treatment, characterized by an outstanding toxicity profile.

PMID- 14585281
TI  - Age-related epigenetic changes and the immune system.
AB  - The role of DNA methylation in immune function is discussed extensively in other
      papers in this issue. Many of these discussions assume that DNA methylation, a
      major mediator of epigenetic information, is fairly immutable and uniform in
      adult cells and tissues. There is, however, growing evidence that DNA methylation
      changes subtly with age. Normal aging cells and tissues show a progressive loss
      of 5-methylcytosine content, primarily within DNA repeated sequences, but also in
      potential gene regulatory areas. In parallel, selected genes show progressive age
      related increases in promoter methylation, which, once a critical methylation
      density is reached, have the potential to permanently silence gene expression.
      These changes are highly mosaic within a given tissue and introduce a high degree
      of epigenetic variability in aging cells. Such epigenetic phenomena could impact
      immune response through masking/unmasking potential tissue antigens as well as by
      modulating the differentiation and response of immune effector cells. The
      contribution of epigenetic changes to the altered immune function observed in
      aging humans deserves careful investigation.

PMID- 14585283
TI  - Deficiency of mannose 6-phosphate receptors and lysosomal storage: a morphometric
      analysis of hepatocytes of neonatal mice.
AB  - Transport of lysosomal enzymes is mediated by two mannose 6-phosphate receptors:
      a cation dependent (CD-MPR) and a cation independent receptor (CI-MPR). In the
      present study the effect of MPR-deficiency on the lysosomal system of neonatal
      mouse hepatocytes was studied by ultrastructural morphometric analyses. The
      volume density of the lysosomal system in hepatocytes of mice that lack both
      receptors was significantly increased in comparison with controls and with mice
      deficient for CI-MPR only. This higher volume density was due to a nine-fold
      increase of residual bodies. In CI-MPR-deficient mice the volume density of the
      lysosomal system was not different from controls and no increase of residual
      bodies was observed. It is concluded that in hepatocytes of MPR-deficient
      neonatal mice lysosomal storage occurs when both MPRs are lacking, whereas
      deficiency of CI-MPR only has no effect on the ultrastructure of the lysosomal
      system.

PMID- 14585284
TI  - New vanadate-induced Ca2+ pathway in human red cells.
AB  - Vanadate is a commonly used Ca2+ pump blocker, exerting a substantial effect on
      Ca2+ extrusion at millimolar concentrations in human red cells. At such levels,
      vanadate also seems to open an L type-like Ca2+ channel in these cells (J Biol
      Chem 257 (1982) 7414; Gen Physiol Biophys 16 (1997) 359). Since neither a dose
      dependence effect nor a metabolic requirement for the latter action could be
      found in the literature, we have addressed this matter in the present work.
      Accordingly, vanadate action on Ca2+ entry was systematically investigated in
      both young and old human red cells after metabolic depletion. Although vanadate
      enhanced Ca2+ entry indifferently in either cell type, a distinct over-all effect
      was paradoxically found depending on whether or not metabolic substrates that
      give rise to ATP were present. In ATP-depleted cells, unlike with ATP-containing
      cells, vanadate-stimulated Ca2+ entry was neither blocked by raising external K+
      nor by adding voltage-dependent Ca2+ channel blockers (nifedipine, calciseptine,
      FTX3.3) or compounds affecting polyphosphoinositide metabolism (Li+, neomycin).
      Likewise, full substitution of external Na+ by other cations did not inhibit
      vanadate-enhanced Ca2+ entry. Regardless of the cell age, stimulation by vanadate
      depended strongly on internal Na+ (0-30 mM). Vanadate stimulation was
      significantly reduced (about 55%) by heparin (10 mg/ml) only in young cells and
      by ryanodine (about 35%, 250 microM) in old cells. The results suggest presence
      of a new vanadate-induced Ca2+ entry pathway in ATP-depleted cells.

PMID- 14585282
TI  - Sensitivity of lysosomal enzymes to the plant alkaloid sanguinarine: comparison
      with other SH-specific agents.
AB  - The influence of the benzo[c]phenanthridine alkaloid sanguinarine on some
      lysosomal enzyme activities was investigated. Sanguinarine inhibits lysosomal
      hydrolases in homogenates of cultured mouse fibroblasts. After incubation of
      mouse fibroblasts in culture with 100 microM sanguinarine an approximately 50%
      decrease in the activities of N-acetyl-beta,D-glucosaminidase (NAGA), beta
      galactosidase (GAL), arylsulfatase and acid lipase was observed. Because the
      biological activity of sanguinarine might arise from the interaction of its
      iminium cation with enzyme thiol groups, we compared its effect on NAGA, GAL and
      acid phosphatase (AcP) activities with the effects of SH-specific reagents p
      chloromercuribenzoic acid (CPMA) and N-ethylmaleimide (NEM). Treatment of
      lysosomal fractions with millimolar concentrations of sanguinarine induces a dose
      dependent inhibition of the enzymes; for example, 0.6 mM sanguinarine causes
      approximately a 40% decrease in AcP and NAGA activities. NEM has similar effects,
      and increasing the preincubation temperature from 0 degrees C to 37 degrees C
      intensifies the inhibition due to both agents. CPMA also inhibits the activity of
      GAL (IC50 0.7 microM), AcP (IC50 12.5 microM) and NAGA (IC50 6.8 microM) in a
      dose-dependent manner but is more potent than sanguinarine or NEM. Comparative
      analysis of the primary structures of these enzymes using the program BLAST
      reveals the presence of highly conserved cysteine residues, which confirms the
      importance of thiol-groups for their activities. Thus, both the experimental
      observations obtained in this study and the literature data imply a significant
      role of redox-based mechanisms in regulating lysosomal functional activity.

PMID- 14585285
TI  - Sulfonated human immunoglobulin enhances CD16-linked CD11b expression on human
      neutrophils.
AB  - Intravenous human immunoglobulin therapy infrequently results in excessive
      inflammatory responses in vivo; these effects are not fully understood. We
      assessed whether sulfonated human immunoglobulin (SHIG) or polyethylene glycol
      treated human immunoglobulin (PHIG) enhanced expression of inflammatory receptors
      on peripheral blood neutrophils in vitro, such as alphaMbeta2 (CD11b/CD18) and Fc
      gamma receptor type III (FcgammaRIII). CD11b and CD16 expression on neutrophils
      was measured by fluorescence flow cytometry. Various cytokines were assessed
      using a highly sensitive fluorescence microsphere system. SHIG enhanced/induced
      CD11b expression and partial aggregations on neutrophils, but PHIG did not. No
      detection of aggregation IgG was observed in SHIG and PHIG. SHIG-induced CD11b
      expression was inhibited by treatment of corticosteroid (dexamethasone) and by
      anti-CD16 monoclonal antibody. Concentrations of various cytokines such as
      interleukin (IL)-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, RANTES, tumor
      necrosis factor (TNF)-alpha, and interferon (INF)-gamma in culture supernatant
      were not significantly changed by SHIG or PHIG. SHIG and PHIG did not enhance
      CD16 on neutrophils. SHIG enhanced CD16-linked CD11b expression on neutrophils in
      vitro. CD11b induction was inhibited by dexamethasone and by anti-CD16 antibody.
      These in vitro results suggest that aggregations and enhancement of CD11b on
      neutrophils by SHIG may induce excessive inflammatory responses in vivo.

PMID- 14585286
TI  - Comparative NMR studies of diffusional water permeability of red blood cells from
      different species: XIV. Little Penguin, Eudyptula minor.
AB  - As part of a programme of comparative measurements of diffusional water
      permeability (Pd) the red blood cells (RBC) from Little Penguin (Eudyptula minor)
      were studied. The cell dimensions were measured with light and electron
      microscopy, and by a newly described non-invasive technique, NMR q-space
      analysis. In view of its relative novelty for cell biologists, an overview of
      this technique is presented. The RBC revealed an ellipsoidal shape that is
      characteristic of avian RBC, with axis lengths ("diameters") estimated to be:
      a=16.0 microm; b=9.6 microm; c=5.0 microm. The values of P(d)were: 2.0 x 10(-3)cm
      s(-1)at 5 degrees C, 3.3 x 10(-3)cm s(-1)at 10 degrees C, 4.6 x 10(-3)cm s(-1)at
      15 degrees C and approximately 5.4 x 10(-3)cm s(-1)at 20, 25, 30, 37 and 42
      degrees C. There was a lack of inhibition of water permeability by p
      chloromercuribenzensulfonate (PCMBS), the well-known inhibitor of RBC aquaporin.
      It was notable that in the temperature range 5-20 degrees C the NMR parameters,
      and hence the permeability, varied linearly as is found for other species, but at
      temperatures higher than 20 degrees C there was no temperature-dependence of Pd.
      Consequently, there was an obvious break at approximately 20 degrees C in the
      Arrhenius plot, of the mean residence life time of water inside the cells, 1/Te,
      versus temperature. For temperatures less than 20 degrees C the activation energy
      E(a,d) was 45.6 +/- 6.6 kJ/mol. For temperatures higher than 25 degrees C E(a,d)
      was zero. The lack of inhibition of water permeability by PCMBS and the very high
      value of E(a,d) for diffusive water exchange suggests that the water permeation
      occurs primarily via the membrane bilayer per se, i.e., there is no aquaporin in
      Little Penguin RBC. The discontinuity at approximately 20 degrees C in the
      Arrhenius plot is an interesting finding, not seen before in other species, and
      we suggest that it reflects a phase transition in the membrane lipids.

PMID- 14585287
TI  - Expression of cell adhesion molecules in the adriamycin-induced esophageal
      atresia rat model.
AB  - Cell adhesion molecules are well-known membrane glycoproteins widely expressed
      during embryonic development that play a crucial role in cell division, migration
      and differentiation. We investigated the cell-matrix relationship using N-CAM and
      pan-cadherin adhesion molecules in the adriamycin-induced esophageal atresia (EA)
      rat model in the hope of finding a clue to the mechanisms of this unique
      anomaly.Time-mated pregnant Sprague-Dawley rats were given either saline or
      adriamycin on days 8 and 9 of gestation. Embryos were harvested on the 18th day
      of gestation. Esophageal specimens obtained from adriamycin-exposed embryos with
      (EA+) or without esophageal atresia (EA-) and from saline-exposed embryos were
      immunostained with N-CAM and pan-cadherin primary antisera. The esophageal
      specimens from control and EA- groups revealed similar immunostaining properties:
      weak N-CAM and pan-cadherin immunoreactivity. In contrast, the EA+ group showed
      intense immunoreactivity. Our study demonstrated an increased synthesis of N-CAM
      and pan-cadherin in the epithelial cells of the atretic esophagus and trachea.
      These results suggest that embryonic cell-cell and cell-matrix interactions may
      play a crucial role in the development of adriamycin-induced EA.

PMID- 14585288
TI  - Loss of hepatocyte co-operative activity after inhibition of ganglioside GM1
      synthesis and shedding.
AB  - Pretreatment of hepatocyte cultures with 1 microM d-l-threo-1-phenyl-2
      hexadecanoylamino-3-pyrrolidino-1-propanol-HCL (PPPP) for 24 h decreased the
      ganglioside GM1 content of the cells by approximately 50% and that of the
      conditioned medium by 90%. No rhythm in the rate of protein synthesis was
      detected in dense cultures pretreated with PPPP, but was observed in control
      dense cultures. Conditioned medium from control dense cultures induced synchrony
      in sparse cultures, which were non-synchronous in their own medium. In contrast,
      conditioned medium from dense cultures pretreated with PPPP did not synchronize
      sparse cultures. Since protein synthesis rhythm is a marker of cell
      synchronization, i.e. their co-operative activity, then non-oscillatory behavior
      means loss of cell co-operation. The protein synthesis rhythm was restored 24 h
      after hepatocytes were transferred to PPPP-free medium. Restoration was more
      rapid when 0.9 microM gangliosides (standard mixture from bovine brain) were
      added to the medium just after the withdrawal of PPPP. These novel results
      concerning the loss of rhythm of protein synthesis in low GM1 ganglioside medium
      support the conclusion that ganglioside is implicated in the regulation of cell
      co-operative activity.

PMID- 14585289
TI  - Green fluorescent protein-labeled mapping of neural stem cells migrating towards
      damaged areas in the adult central nervous system.
AB  - Neural stem cells, which are clonogenic cells with multilineage differentiation
      properties from regions of the fetal brain, cortex and hippocampus, are currently
      considered as powerful candidates for cell replacement therapy in
      neurodegenerative disorders, such as Parkinson's disease. A key issue is whether
      stem cells can survive, migrate and differentiate following transplantation into
      the adult CNS. Here, enhanced green fluorescent protein plasmid electroporation
      transfected neural stem cells from the fetal cortex were grafted into the
      striatum of a rat model of Parkinson's disease. We found most of the grafted
      cells could survive in the adult parkinsonian rat brain and migrated towards
      damaged areas, while they moved randomly in the normal brain. Several grafted
      cells differentiated into neurons.

PMID- 14585290
TI  - Sterol glucosyltransferases have different functional roles in Pichia pastoris
      and Yarrowia lipolytica.
AB  - Mutants of the methanol-utilizing yeast Pichia pastoris and the alkane-utilizing
      yeast Yarrowia lipolytica defective in the orthologue of UGT51 (encoding sterol
      glucosyltransferase) were isolated and compared. These mutants do not contain the
      specific ergosterol derivate, ergosterol glucoside. We observed that the P.
      pastoris UGT51 gene is required for pexophagy, the process by which peroxisomes
      containing methanol-metabolizing enzymes are selectively shipped to and degraded
      in the vacuole upon shifting methanol-grown cells of this yeast to glucose or
      ethanol. PpUGT51 is also required for other vacuole related processes. In
      contrast, the Y. lipolytica UGT51 gene is required for utilization of decane, but
      not for pexophagy. Thus, sterol glucosyltransferases play different functional
      roles in P. pastoris and Y. lipolytica.

PMID- 14585291
TI  - Processing of metaphoric and non-metaphoric alternative meanings of words after
      right- and left-hemispheric lesion.
AB  - This study examines the specificity of the contribution of the right hemisphere
      to the processing of metaphoric meaning of words. Ten right- and 10 left
      hemisphere-damaged subjects, and 20 normal control subjects were submitted to:
      (1) a word-triad task where they had to associate alternative metaphoric and non
      metaphoric words to a target word, and to (2) a word-dyad task where they had to
      decide whether or not there was a semantic relationship between two words. The
      two tasks aimed at differentiating between the subjects' preference for a given
      semantic meaning versus a genuine semantic deficit for a particular meaning.
      Results revealed that both right- and left-hemisphere-damaged groups presented a
      genuine semantic deficit for the processing of metaphoric meaning. The absence of
      a double dissociation between the two brain-damaged groups does not support the
      hypothesis of a specific contribution of the right-hemisphere to the processing
      of metaphoric meaning of words.

PMID- 14585292
TI  - Lateralization effects during semantic and rhyme judgement tasks in deaf and
      hearing subjects.
AB  - A visual hemifield experiment investigated hemispheric specialization among
      hearing children and adults and prelingually, profoundly deaf youngsters who were
      exposed intensively to Cued Speech (CS). Of interest was whether deaf CS users,
      who undergo a development of phonology and grammar of the spoken language similar
      to that of hearing youngsters, would display similar laterality patterns in the
      processing of written language. Semantic, rhyme, and visual judgement tasks were
      used. In the visual task no VF advantage was observed. A RVF (left hemisphere)
      advantage was obtained for both the deaf and the hearing subjects for the
      semantic task, supporting Neville's claim that the acquisition of competence in
      the grammar of language is critical in establishing the specialization of the
      left hemisphere for language. For the rhyme task, however, a RVF advantage was
      obtained for the hearing subjects, but not for the deaf ones, suggesting that
      different neural resources are recruited by deaf and hearing subjects. Hearing
      the sounds of language may be necessary to develop left lateralised processing of
      rhymes.

PMID- 14585293
TI  - Phonological memory and vocabulary learning in children with focal lesions.
AB  - Eleven children with early focal lesions were compared with 70 age-matched
      controls to assess their performance in repeating non-words, in learning new
      words, and in immediate serial recall, a triad of abilities that are believed to
      share a dependence on serial ordering mechanisms (e.g.,; ). Results for the
      experimental group were also compared with other assessments previously reported
      for the same children by. The children with brain injury showed substantial
      impairment relative to controls in the experimental tasks, in contrast with
      relatively unimpaired performance on measures of vocabulary and non-verbal
      intelligence. The relationships between word learning, non-word repetition, and
      immediate serial recall were similar to those observed in several other
      populations. These results support previous reports that there are persistent
      processing impairments following early brain injury, despite developmental
      plasticity. They also suggest that word learning, non-word repetition, and
      immediate serial recall may be relatively demanding tasks, and that their
      relationship is a fundamental aspect of the cognitive system.

PMID- 14585294
TI  - Lateralized effects of subthalamic nucleus stimulation on different aspects of
      speech in Parkinson's disease.
AB  - In this report, we have analyzed the effects of left and right STN stimulation
      separately on different aspects of speech. Significant differences were found
      between left and right stimulation. It appears that selective left-sided
      stimulation has a profoundly negative effect on prosody, articulation and hence
      intelligibility. Right-sided stimulation does not display this side-effect. There
      is no significant difference in speech characteristics between bilateral
      stimulation on and off. We suggest that a balanced tuning of bilateral basal
      ganglia networks is necessary for speech, and that the left circuit is probably
      dominant.

PMID- 14585295
TI  - Impaired sensitivity to dynamic stimuli in poor readers of a regular orthography.
AB  - The mappings from grapheme to phoneme are much less consistent in English than
      they are for most other languages. Therefore, the differences found between
      English-speaking dyslexics and controls on sensory measures of temporal
      processing might be related more to the irregularities of English orthography
      than to a general deficit affecting reading ability in all languages. However,
      here we show that poor readers of Norwegian, a language with a relatively regular
      orthography, are less sensitive than controls to dynamic visual and auditory
      stimuli. Consistent with results from previous studies of English-readers,
      detection thresholds for visual motion and auditory frequency modulation (FM)
      were significantly higher in 19 poor readers of Norwegian compared to 22 control
      readers of the same age. Over two-thirds (68.4%) of the children identified as
      poor readers were less sensitive than controls to either or both of the visual
      coherent motion or auditory 2Hz FM stimuli.

PMID- 14585296
TI  - Sensitivity to gender, person, and tense inflection by persons with Alzheimer's
      disease.
AB  - This paper investigates sensitivity to gender, person, and tense inflection in
      individuals with Alzheimer's disease (AD) in on-line and off-line tasks. Fourteen
      persons with AD and 14 matched controls participated in two studies: sensitivity
      to gender incongruity was tested in an on-line reading task and sensitivity to
      violation of tense and person was tested with an off-line grammaticality
      judgement test. Group performance was comparable on both tasks. It is argued that
      patients' preserved sensitivity to these features is primarily a function of the
      simplicity of the required operations. The notion of simplicity in this context
      is discussed and various parameters are offered for future investigation.

PMID- 14585297
TI  - Sensitivity to prosodic structure in left- and right-hemisphere-damaged
      individuals.
AB  - An experiment was conducted in order to determine whether left- (LHD) and right
      hemisphere-damaged (RHD) patients exhibit sensitivity to prosodic information
      that is used in syntactic disambiguation. Following the work of, a cross-modal
      lexical decision task was performed by LHD and RHD subjects, as well as by adults
      without brain pathology (NC). Subjects listened to sentences with attachment
      ambiguities with either congruent or incongruent prosody, while performing a
      visual lexical decision task. Results showed that each of the unilaterally
      damaged populations differed from each other, as well as from the NCs in terms of
      sensitivity regarding prosodic cues. Specifically, the RHD group was insensitive
      to sentence prosody as a whole. This was in contrast to the LHD patients, who
      responded to the prosodic manipulation, but in the unexpected direction. Results
      are discussed in terms of current hypotheses regarding the hemispheric
      lateralization of prosodic cues.

PMID- 14585298
TI  - Accessing word meaning in two languages: an event-related brain potential study
      of beginning bilinguals.
AB  - Twenty-eight native-English speakers enrolled in beginning and intermediate
      university Spanish courses participated in a mixed language semantic
      categorization task in which critical words were presented in English (L1) and
      Spanish (L2) and repetitions of these words (within- and between-languages) were
      presented on subsequent trials (i.e., immediate repetition). Event-related
      potentials were recorded to all items allowing for comparisons of the N400
      component to repetitions within- and between-languages as well as to words
      presented for the first time. Three important findings were observed in this
      sample of participants during relatively early stages of acquiring a second
      language. First, in the typical N400 window (300-500ms), between-language
      repetition (translation) produced a smaller reduction in N400 amplitude than did
      within-language repetition. Second, the time-course of between-language
      repetition effects tended to be more extended in time and differed as a function
      of language with L2-L1 repetitions producing larger priming effects early (during
      the typical N400 window) and L1-L2 repetitions producing larger priming effects
      later (during windows after the typical N400). Third, a greater negativity in the
      ERP waveforms was observed when the word on the directly preceding trial was from
      the other language. Within the time frame of the N400, this language switch
      effect arose only when the target word was Spanish and the preceding word English
      (i.e., L1-L2). The results are discussed within the framework of current models
      of bilingual lexical processing.

PMID- 14585299
TI  - Ease of predication does not account for imageability effects in performance: a
      reply to Jones (2002).
AB  - In this paper we defend our views against claim that the criticism of the ease of
      predication hypothesis (Jones, 1985) made by de Mornay Davies and Funnell (2000)
      is "fundamentally flawed." Jones raises five issues concerning the content of the
      text, the reliability of effects of ease of predication, the generation of
      predicates, semantic features, and memory retrieval. We address each of these
      issues in turn and show that either a critical point raised is not made, or the
      point is mistaken. More importantly we show that our empirical findings, which
      are entirely overlooked by Jones, unequivocally support the view that ease of
      predication does not account for imageability effects in performance.

PMID- 14585300
TI  - Verb reading in developmental language impairment.
AB  - This research addresses the issues of frequency and regularity in verb reading
      and their importance for the organization of the mental lexicon in DLI
      francophones. A reading task probes response latencies and response accuracy for
      DLI and control participants on frequent and infrequent inflected forms of verbs.
      DLI participants are slower at reading verbs even if their mean accuracy rates
      are higher than controls'. Results also indicate that the type of suffix on the
      verb affects controls and DLI participants differently in their accuracy rates:
      DLI participants exhibit higher error rates on less frequent inflections, while
      controls do not. Finally, unusual patterns are found for DLI participants on
      regular versus irregular verbs: regular verbs are slower to be read by DLI
      participants. These results are compared to findings from a previous simple
      lexical decision study. They are interpreted as indicating that DLI word reading
      patterns are qualitatively different from those evidenced by controls.

PMID- 14585301
TI  - Does morphology make the difference? Agrammatic sentence comprehension in German.
AB  - This study examines the syntactic comprehension of seven German agrammatic
      speakers. The German language allows the study of the interaction of syntactic
      principles and morphological devices in the comprehension process. In addition,
      due to its relatively free word order, German allows the study of strictly
      minimal pairs of canonical and non-canonical sentences in addition to the rather
      controversial active-passive contrast. A central research question was whether
      the pattern of agrammatic comprehension predicted by the trace deletion
      hypothesis (TDH, Grodzinsky, 1990, 1995), relatively normal comprehension
      performance of canonical sentences and chance performance on non-canonical
      sentences, can be found in a language with richer morphology than English. The
      generalisability of the TDH-pattern to morphologically rich languages is not
      obvious, given that case morphology in particular can provide explicit cues to
      the detection of the agent and patient roles in a sentence. The results of this
      study indicate that morphology does not make a difference. Furthermore, the group
      results are in line with the TDH-predictions only for number marked sentences but
      not for case marked sentences. However, single case analysis reveals different
      patterns of syntactic comprehension in agrammatic patients, a spectrum that
      encompasses near-normal comprehension of canonical and non-canonical sentences,
      overall chance performance, and TDH-like profiles.

PMID- 14585302
TI  - Human requirements for fat-soluble vitamins, and other things concerning these
      nutrients.

PMID- 14585303
TI  - The role of alpha-tocopherol in preventing disease: from epidemiology to
      molecular events.
AB  - The function of vitamin E has been attributed to its capacity to protect the
      organism against the attack of free radicals by acting as a lipid based radical
      chain breaking molecule. More recently, alternative non-antioxidant functions of
      vitamin E have been proposed and in particular that of a "gene regulator".
      Effects of vitamin E have been observed at the level of mRNA or protein and could
      be consequent to regulation of gene transcription, mRNA stability, protein
      translation, protein stability and post-translational events. Given the high
      priority functions assigned to vitamin E, it can be speculated that it would be
      inefficient to consume it as a radical scavenger. Rather, it would be important
      to protect vitamin E through a network of cellular antioxidant defences,
      similarly to what occurs with proteins, nucleic acids and lipids.

PMID- 14585304
TI  - Homologous metabolic and gene activating routes for vitamins E and K.
AB  - Vitamins E and K share structurally related side chains and are degraded to
      similar final products. For vitamin E the mechanism has been elucidated as
      initial omega-hydroxylation and subsequent beta-oxidation. For vitamin K the same
      mechanism can be suggested analogously. omega-Hydroxylation of vitamin E is
      catalyzed by cytochrome p450 enzymes, which often are induced by their substrates
      themselves via the activation of the nuclear receptor PXR. Vitamin E is able to
      induce CYP3A-forms and to activate a PXR-driven reporter gene. It is shown here
      that K-type vitamins are also able to activate PXR. A ranking showed that
      compounds with an unsaturated side chain were most effective, as are tocotrienols
      and menaquinone-4 (vitamin K(2)), which activated the reporter gene 8-10-fold.
      Vitamers with a saturated side chain, like tocopherols and phylloquinone were
      less active (2-5-fold activation). From the fact that CYPs commonly responsible
      for the elimination of xenobiotics are involved in the metabolism of fat-soluble
      vitamins and the ability of the vitamins to activate PXR it can be concluded that
      supranutritional amounts of these vitamins might be considered as foreign.

PMID- 14585305
TI  - Antioxidant activity of carotenoids.
AB  - Carotenoids are pigments which play a major role in the protection of plants
      against photooxidative processes. They are efficient antioxidants scavenging
      singlet molecular oxygen and peroxyl radicals. In the human organism, carotenoids
      are part of the antioxidant defense system. They interact synergistically with
      other antioxidants; mixtures of carotenoids are more effective than single
      compounds. According to their structure most carotenoids exhibit absorption
      maxima at around 450 nm. Filtering of blue light has been proposed as a mechanism
      protecting the macula lutea against photooxidative damage. There is increasing
      evidence from human studies that carotenoids protect the skin against
      photooxidative damage.

PMID- 14585306
TI  - Prooxidant effects of beta-carotene in cultured cells.
AB  - There is a growing body of interest on the role of beta-carotene and other
      carotenoids in human chronic diseases, including cancer. While epidemiological
      evidence shows that people who ingest more dietary carotenoids exhibit a reduced
      risk for cancer, results from intervention trials indicate that supplemental beta
      carotene enhances lung cancer incidence and mortality among smokers. A possible
      mechanism which can explain the dual role of beta-carotene as both a beneficial
      and a harmful agent in cancer as well as in other chronic diseases is its ability
      in modulating intracellular redox status. beta-Carotene may serve as an
      antioxidant or as a prooxidant, depending on its intrinsic properties as well as
      on the redox potential of the biological environment in which it acts. This
      review summarizes the available evidence for a prooxidant activity of beta
      carotene in cultured cells, focusing on biochemical and molecular markers of
      oxidative stress, which have been reported to be enhanced by the carotenoid.

PMID- 14585307
TI  - Carotenoids as prooxidants?

PMID- 14585308
TI  - Modulation of transcriptional activity by antioxidant carotenoids.
AB  - It is widely accepted that diet changes are a powerful means to prevent cancer.
      The possible involvement of transcriptional activity in the anticancer activity
      of carotenoids will be the focus of this review. Carotenoids function as potent
      antioxidants, and this is clearly a major mechanism of their action. In addition
      carotenoids action involves interference in several pathways related to cancer
      cell proliferation and includes changes in the expression of many proteins
      participating in these processes such as connexins, phase II enzymes, cyclins,
      cyclin-dependent kinases and their inhibitors. These changes in protein
      expression suggest that the initial effect involves modulation of transcription
      by ligand-activated nuclear receptors or by other transcription factors. It is
      feasible to suggest that carotenoids and their oxidized derivatives interact with
      a network of transcription systems that are activated by different ligands at low
      affinity and specificity and that this activation leads to the synergistic
      inhibition of cell growth.

PMID- 14585309
TI  - Rosehip -- a "new" source of lycopene?
AB  - Lycopene, an efficient antioxidant and singlet oxygen quencher, is mainly
      delivered within the human diet out of tomatoes and tomato products. Processing
      liberates this carotenoid from complexes with proteins and thus makes it more
      bioavailable. Rosehip, a wild fruit which is used more often recently to produce
      mark, jams and juices, showed remarkable contents of lycopene (12.9-35.2 mg/100
      g) with an unexpected isomer pattern.

PMID- 14585310
TI  - Effects of vitamin E and carotenoid status on oxidative stress in health and
      disease. Evidence obtained from human intervention studies.
AB  - Vitamin E and carotenoids are known to act as antioxidants both in vitro and in
      vivo. In this review we present a series of studies in healthy subjects and in
      patients who exhibit either acute or chronic oxidative stress. In the EU
      Commission funded VITAGE project we investigated the status and effects of
      vitamin E and carotenoids on oxidative stress in 300 healthy volunteers.
      Depletion studies limiting dietary vitamin E or carotenoid intake to
      approximately 25% of the dietary reference intakes and subsequent repletion by
      supplementation with either large doses of vitamin E or intermediate doses of
      carotenoids showed significant changes in ex vivo LDL oxidizability, total plasma
      peroxide concentrations and urinary 8-oxo-7,8-dihydro-2(')-deoxyguanosine
      excretion. Patients on chronic hemodialysis present with oxidative stress in the
      presence of normal vitamin E but impaired vitamin C status and, due to anemia,
      need to be treated with parenteral iron. We studied the effects of a single oral
      dose of vitamin E taken 6 h prior to intravenous infusion of 100 mg iron, which
      exceeded the iron-binding capacity of transferrin. Vitamin E significantly
      reduced and in combination with a single dose of vitamin C completely abrogated
      acute oxidative stress induced by the iron load. Patients with cystic fibrosis
      are exposed to chronic oxidative stress due to an overproduction of reactive
      oxygen species as a result of neutrophil-dominated lung inflammation and impaired
      antioxidant status. Biochemical vitamin E and carotenoid deficiencies could be
      fully corrected even in the presence of fat malabsorption using intermediate
      doses of either RRR alpha-tocopherol or all-rac alpha-tocopheryl acetate and
      water-miscible all-trans beta-carotene. Long-term supplementation reduced ex vivo
      LDL oxidizability, in vivo lipid peroxidation and lung inflammation.

PMID- 14585311
TI  - Structure and function of retinol dehydrogenases of the short chain
      dehydrogenase/reductase family.
AB  - All-trans-retinol is the common precursor of the active retinoids 11-cis-retinal,
      all-trans-retinoic acid (atRA) and 9-cis-retinoic acid (9cRA). Genetic and
      biochemical data supports an important role of the microsomal members of the
      short chain dehydrogenases/reductases (SDRs) in the first oxidative conversion of
      retinol into retinal. Several retinol dehydrogenases of this family have been
      reported in recent years. However, the structural and functional data on these
      enzymes is limited. The prototypic enzyme RDH5 and the related enzyme CRAD1 have
      been shown to face the lumen of the endoplasmic reticulum (ER), suggesting a
      compartmentalized synthesis of retinal. This is a matter of debate as a related
      enzyme has been proposed to have the opposite membrane topology. Recent data
      indicates that RDH5, and presumably other members of the SDRs, occur as
      functional homodimers, and need to interact with other proteins for proper
      intracellular localization and catalytic activity. Further analyses on the
      compartmentalization, membrane topology, and functional properties of microsomal
      retinol dehydrogenases, will give important clues about how retinoids are
      processed.

PMID- 14585312
TI  - Vitamin A transport: in vitro models for the study of RBP secretion.
AB  - Retinol-binding protein (RBP) is the specific plasma carrier of retinol,
      encharged of the vitamin transport from the liver to target cells. Ligand binding
      influences the RBP affinity for transthyretin (TTR), a homotetrameric protein
      involved in the RBP/TTR circulating complex, and the secretion rate of RBP. In
      fact, in vitamin A deficiency, the RBP release from the hepatocytes dramatically
      decreases and the protein accumulates in the cells, until retinol is available
      again. The mechanism is still not clear and new cellular models are needed to
      understand in detail how the soluble RBP can be retained inside the cell. In
      fish, a vitamin A transport system similar to that of higher vertebrates is
      emerging, although with significant differences.

PMID- 14585313
TI  - Understanding the physiological role of retinol-binding protein in vitamin A
      metabolism using transgenic and knockout mouse models.
AB  - Retinoids (vitamin A and its derivatives) play an essential role in many
      biological functions. However mammals are incapable of de novo synthesis of
      vitamin A and must acquire it from the diet. In the intestine, dietary retinoids
      are incorporated in chylomicrons as retinyl esters, along with other dietary
      lipids. The majority of dietary retinoid is cleared by and stored within the
      liver. To meet vitamin A requirements of tissues, the liver secretes retinol
      (vitamin A alcohol) into the circulation bound to its sole specific carrier
      protein, retinol-binding protein (RBP). The single known function of this protein
      is to transport retinol from the hepatic stores to target tissues. Over the last
      few years, the generation of knockout and transgenic mouse models has
      significantly contributed to our understanding of RBP function in the metabolism
      of vitamin A. We discuss below the role of RBP in maintaining normal vision and a
      steady flux of retinol throughout the body in times of need.

PMID- 14585314
TI  - Importance of vitamin-A for lung function and development.
AB  - Vitamin-A is essential for growth and development of cells and tissues. In its
      active form, retinoic acid, it controls the regular differentiation as a ligand
      for retinoic acid receptors (RAR, RXR) and is involved in the integration (gap
      junction formation) of cell formations [Nature 37 (1994) 528; International
      Review of Cytology. San Diego Academic Press, 1-31]. Vitamin-A plays a
      substantial role, especially in the respiratory epithelium and the lung. During
      moderate vitamin-A-deficiency, the incidence for diseases of the respiratory
      tract is considerably increased and repeated respiratory infections can be
      influenced therapeutically by a moderate vitamin-A-supplementation [Aust.
      Paediatr. J. 22 (1986) 95; Lancet 338 (1991) 67]. In addition to the importance
      of the vitamin for the lung function, vitamin-A is also responsible for the
      development of many tissues and cells as well as for the embryonic lung
      development. Recent studies proved that the control occurs by different
      expressions of retinoid receptors as well as by time-dependent changes of the
      vitamin-A-metabolism respectively via cellular vitamin-A-binding proteins (CRBP:
      cytoplasmatic retinol binding protein; CRABP: cytoplasmatic retinoic acid binding
      protein).

PMID- 14585315
TI  - Carotenoid and retinoid transport to fish oocytes and eggs: what is the role of
      retinol binding protein?
AB  - Fish eggs contain carotenoids, retinals (retinal and dehydroretinal) and retinols
      (retinol, dehydroretinol and retinyl-esters) that are utilized during embryonic
      development, after fertilization. The carotenoids (mainly astaxanthins) are
      transported in the plasma by the low density lipoproteins, high density
      lipoproteins, and very high density lipoproteins (VHDL) and were found to be
      associated also with serum albumin. Retinals were found to be associated
      vitellogenin (VTG), a component of the plasma VHDL fraction that is internalized
      by oocytes during vitellogenesis. However, the transport of retinols and retinyl
      esters that were located in the oil droplet fraction of homogenized eggs, has yet
      to be elucidated. Retinols are more abundant in freshwater fish eggs than in eggs
      of marine fish species. Since retinol is transported in the plasma of vertebrates
      in association with retinol binding protein (RBP), recent studies on the
      molecular characterization and expression sites of RBP, could contribute to
      determining the involvement of RBP in transporting retinol to developing oocytes
      in vertebrates.Recently, results from our laboratory show that RBP mRNA levels in
      the liver and RBP plasma levels did not significantly change with the onset and
      during vitellogenesis in the Rainbow trout. These results were in contrast with a
      dramatic elevation in the mRNA levels of VTG in the liver and an increase in VTG
      plasma levels that was observed in the same females. Moreover, 17beta-estradiol
      treatment of immature fish, resulted in relatively lower mRNA levels of RBP in
      the liver, concomitantly with an increase in the level of VTG transcripts and the
      appearance of VTG in the plasma of treated fish. In addition, RBP was localized
      in the cytosol of ovulated oocytes. These results for Rainbow trout are similar
      to those reported for the chicken but differ from those of Xenopus, where an
      increase in RBP mRNA was reported in the liver and higher levels of retinal and
      retinol were found in the plasma of 17beta-estradiol treated animals. The
      results, reported here for the first time in Rainbow trout, showing RBP
      transcripts in the ovary, oviduct (the ovarian tissue adjacent to the gonopore)
      and oocytes, suggest a modulating role for RBP in follicular development, as has
      been suggested for the bovine ovary.

PMID- 14585316
TI  - Regulation of extrarenal synthesis of 1,25-dihydroxyvitamin D3--relevance for
      colonic cancer prevention and therapy.
AB  - Epidemiological studies have demonstrated a high incidence of colonic tumors in
      populations living in areas of low sunlight exposure. This suggests 1,25
      dihydroxyvitamin D3, an antimitotic prodifferentiating steroid hormone, as a
      potentially preventive factor since levels of the precursor 25-hydroxyvitamin D3
      in serum are, to a major part, dependent upon sun exposure. Conversion into the
      active metabolite from the precursor is effected by CYP27B1, and degradation by
      CYP24. Both p450 hydroxylases are known to be located in the kidney. However, we
      were able to demonstrate presence, and activity of both enzymes also in the
      colon. We have shown also that during early tumor progression expression of
      CYP27B1 and of the vitamin D receptor is upregulated. Therefore the vitamin D
      system may function as a potent physiological defense against further tumor
      progression in cancer patients. We suggest that estrogenic substances, and also
      phytoestrogens present in soy food could, by increasing tumor tissue-located
      CYP27B1 activity and decreasing degradative CYP24 activity, augment tumor
      localized 1,25-dihydroxyvitamin D3 levels and activity.

PMID- 14585317
TI  - Androgen receptor CAG repeat polymorphism in prostate cancer from a Brazilian
      population.
AB  - Shorter CAG repeats in the androgen receptor (AR) gene have been associated with
      increased prostate cancer risk. Aiming to investigate whether the AR CAG
      polymorphism is associated with an increased relative risk for prostate cancer in
      our population, genomic DNA from 133 prostate cancer patients and 279 healthy men
      controls were examined. We found no association between the AR CAG polymorphism
      and the relative risk of prostate cancer in white Brazilian individuals with a
      CAG repeat length </=21. Our results show that in the studied population the
      Asian-descendants have the highest, the white an intermediate and the black a
      tendency to the lowest CAG repeats rates. We observed a significant correlation
      between a lower number of CAG repeats and young age at diagnosis (P=0.034). This
      study is the first to investigate the association between the AR CAG repeat
      polymorphism and the relative risk of prostate cancer in the Brazilian
      population.

PMID- 14585318
TI  - Effects of 0.2 T static magnetic field on human skin fibroblasts.
AB  - Human skin fibroblasts were exposed to 0.2 T static magnetic field generated by a
      magnetic resonance tomograph. After 1h exposure, cell morphology was modified in
      association with a concomitant decrease in the expression of some sugar residues
      of glycoconjugates. Study of cell proliferation and mitogenic signal transduction
      showed a decrease of thymidine incorporation and of second messenger formation.
      However, cell viability, assessed by colony forming assay, was unaffected. These
      results demonstrate that the static magnetic field generated by routinely used
      magnetic resonance tomograph induces alterations on human skin fibroblasts.

PMID- 14585319
TI  - Annual screening for oral cancer detection.
AB  - Most oral cancer and oral mucosal screening programs initiated in the past 20
      years have been limited to a single examination of the population under study.
      Age specific, annual oral mucosal screening examination as a part of general
      health screening has been in operation in Tokonama city, Japan, from 1986. From
      1996 the same target population aged 40 years and older has been invited for
      screening. The program coverage extended to 26% of the city population. During
      1995-1998, out of 9536 attendees who participated in a general health and oral
      mucosal screening program in Tokoname city 6340 subjects (66.5%) re-attended at
      least for one further screening examination. There was no difference in the
      attendance for two annual mucosal examinations between male (67.0%) and female
      (66.2%) subjects. Three thousand nine hundred thirty-five subjects attended oral
      screening all 3 years (1996-1999) and the overall show-up rate for three
      consecutive examinations was 61%. During September-October 1996, 42 volunteer
      dentists carried out 6705 mouth examinations among those aged 40 years and older
      at the Municipal Center. One oral cancer was detected in 1996, in a subject free
      of any mucosal disease in the previous year. Among the screen-negative cases in
      1996, 78% re-attended for screening in 1997 and 79% re-attended in the subsequent
      year. In the cohort that re-attended screening (1996-1998), oral mucosal
      pathology detected in three consecutive screenings included 18 leukoplakias, 24
      with oral lichen planus and 343 other benign mucosal lesions. The number of
      subjects who complied to return and who remained disease-free over the 3-year
      period amounted to 3860, 59% of the disease-free subjects seen in 1996. A regular
      smoker was less likely to attend oral cancer screening in the three consecutive
      years of follow-up (odds ratio: 0.832, 95% CI 0.701-0.988). Satisfactory
      participation can be obtained for annual oral mucosal screening in Japan: this
      allows detection of new lesions, including oral cancer and leukoplakia (a
      surrogate marker of cancer risk). The number of new oral cancers detected in the
      program was too low to determine the optimal frequency for oral cancer screening
      but new oral leukoplakias were found on annual re-screening: the data indicate
      that the interval between two screens for this population should not be greater
      than 12 months.

PMID- 14585321
TI  - Information needs about hereditary breast cancer among women with early-onset
      breast cancer.
AB  - To explore hereditary breast cancer (HBC) information needs of early-onset breast
      cancer survivors, two questionnaires were mailed to women diagnosed at age <50
      years. The Family History Questionnaire, sent to women treated at 34 Virginia
      hospitals, was designed to identify women with suspected HBC versus women with
      presumed sporadic breast cancer (SBC). Among 314 respondents, 137 reported
      personal/family histories suggestive of HBC. A total of 287 (87%) participants
      responded to the subsequent Knowledge, Attitudes, and Beliefs Questionnaire,
      which assessed HBC knowledge, attitudes, and beliefs, including HBC information
      needs, sources, and perceived value. Fifty-two percent of women reported seeking
      any HBC information. Women with presumed SBC were as likely to seek information
      as those with suspected HBC. Women with daughters were more likely to seek
      information. Many (71%) women reported finding the information sought, including
      information about their children's and relatives' risks, DNA testing, treatment
      differences for HBC, and genetic counseling.

PMID- 14585320
TI  - The association between counseling, sun protection, and early detection of skin
      cancer in middle-aged Israelis.
AB  - BACKGROUND: Healthcare professionals' counseling is expected to prompt primary
      and secondary prevention of skin cancer. In this study, we evaluated the
      association between counseling on skin cancer prevention and early detection and
      the recommended behaviors in middle-aged people. METHODS: A random national cross
      sectional telephone survey of 793 Israeli residents, aged 45-75 years, was
      conducted. The interviewees reported healthcare professionals' counseling and
      self-reported behaviors associated with sun protection and early detection of
      skin cancer. RESULTS: Counseling on sun protection was reported by less than 10%
      of respondents. The presence of self-reported skin-cancer risk factors was
      significantly associated both with sun protection counseling and behavior.
      However, there was no association between sun protection counseling and behavior
      in a regression model. The rate of counseling on self-skin examination among
      respondents with self-reported skin-cancer risk factors was 17%. Early detection
      behaviors were significantly associated with practitioner's counseling on this
      issue. CONCLUSION: Healthcare professionals' counseling on secondary skin cancer
      prevention seems to have a greater impact on behaviors than primary prevention
      counseling in middle-aged people and calls for improvement of primary prevention
      by health care professionals.

PMID- 14585322
TI  - Health beliefs, salience of breast cancer family history, and involvement with
      breast cancer issues: adherence to annual mammography screening recommendations.
AB  - Involvement in breast cancer (BC) issues, and the degree to which family history
      of BC influences perceived risk (salience of family history), have been proposed
      as additions to the Health Belief Model as applied to mammography adherence.
      Barriers and benefits of mammography, perceived susceptibility, severity, cues to
      action, salience of family history, and issue involvement with respect to BC were
      examined in adherent (n=97) and non-adherent (n=213) women. Adherent women with
      positive family histories reported greater benefits of mammography, greater
      response to cues to action, and higher salience of family history than women with
      negative family histories. Non-adherent women with positive family histories
      reported fewer benefits of mammography and greater issue involvement, and
      perceived BC as less severe than those with negative family histories. Benefits
      (OR=1.51), susceptibility (OR=1.41), issue involvement (OR=1.59), severity
      (OR=0.66), and cues to action (OR=0.75) were significantly associated with
      adherence. Results have implications for evidence-based interventions.

PMID- 14585323
TI  - Service screening with mammography of women aged 70-74 years in Sweden. Effects
      on breast cancer mortality.
AB  - Since the benefit of mammography screening for women 70 years and older is
      unclear, the aim of the present study was to evaluate the effect on breast cancer
      mortality of the population-based service-screening program in Sweden inviting
      women 70-74 years. Among the counties with service-screening programs in Sweden
      which started 1986-1990 those with upper age limit 74 years were compared to
      counties with 69 years as upper age limit with respect to refined breast cancer
      mortality. Allowance was made for potential biases namely inclusion of cases
      diagnosed before invitation and lead time. Two methods for estimation of breast
      cancer mortality were used; underlying cause of death (UCD) and excess mortality.
      With a mean follow-up of 10.1 years a reduction of the breast cancer excess
      mortality was estimated at 24%. Using the underlying cause of death the
      corresponding result was 6%. A non-significant reduction in breast cancer
      mortality was found in the counties with service-screening program including the
      age group 70-74 years in Sweden. The estimated reduction was larger when using
      excess mortality compared to the use of individual underlying cause of death.

PMID- 14585324
TI  - Prevention of chemical carcinogen DNA binding and inhibition of nuclear RNA
      polymerase activity by organosulfur compounds as the possible mechanisms for
      their anticancer initiation and proliferation effects.
AB  - This report examines the transcriptional roles and DNA binding properties of the
      three major organosulfur compounds (OSCs) from garlic, diallyl sulfide (DAS),
      diallyl disulfide (DADS) and diallyl trisulfide (DATS). We found DADS and DATS,
      but not DAS, could be activated by the versatile epoxide-forming oxidant
      dimethyldioxirane (DMDO) and could strongly inhibit nuclear RNA synthesis in
      vitro. We also found that when incubated together with [3H]-labeled 17beta
      estradiol (E(2)) for activation by DMDO, DADS and DATS, but not DAS, were able to
      prevent the binding of [3H]E(2) to DNA. This preventive effect of DADS and DATS
      was confirmed when liver microsomes were used, and further verified by 32P post
      labeling analysis. Additionally, we discovered that the DMDO treated DADS and
      DATS, but not DAS, were able to directly inhibit the enzyme RNA polymerase per
      se. These novel findings provide new insights into the potential mechanisms of
      the preventive effects of OSCs on tumor initiation and promotion.

PMID- 14585325
TI  - Restoration of an impaired TGF-beta1 autocrine growth-inhibitory circuit results
      in growth inhibition of ovarian epithelial cancer cells and complete inhibition
      of their tumorigenicity.
AB  - The disruption of the transforming growth factor beta1 (TGF-beta1) autocrine
      growth-suppressive circuit is a major and possibly early event mediating the
      malignant transformation of normal epithelia. TGF-beta1 is secreted as a latent
      homodimer-peptide that, upon activation, binds a receptor complex. This in turn
      activates a signal transduction cascade that results in proliferation inhibition
      of epithelial cells. The growth-inhibitory pathway can be interrupted at several
      levels: insufficient secretion and activation of TGF-beta1 ligand, mutational
      inactivation of the receptors or signal transduction intermediates or at the
      level of the nuclear effector molecules. We have investigated the effect of
      restoring the growth-inhibitory autocrine circuit in epithelial cancer cells that
      have retained sensitivity to growth inhibition by TGF-beta1 but which produce and
      secrete insufficient amounts of endogenous peptide. These cancer cells were
      transduced with a recombinant adenovirus containing a TGF-beta1 cDNA driven by a
      CMV promoter and coding for a constitutively bioactive TGF-beta1 peptide.
      Restituting the TGF-beta1 autocrine growth-suppressive circuit in these cancer
      cells had a potent growth-inhibitory effect in vitro. Moreover, in vitro
      transduced cells lost their tumorigenicity in nude mice. As disruption of TGF
      beta's autocrine growth circuit is thought to be an early event in the malignant
      transformation of several epithelial cancers, early correction of this defect
      might in the future lead to cancer preventive strategies.

PMID- 14585326
TI  - Multifactorial activities of nonsteroidal antiestrogens against leukemia.
AB  - The antileukemic activity of nonsteroidal antiestrogens was investigated.
      Tamoxifen, clomiphene and nafoxidine caused a decrease in viability of the
      estrogen receptor-negative T-lymphoblastic leukemia cell line CCRF/CEM,
      nafoxidine being the most active. A combination of clomiphene and genistein
      resulted in a synergistic cytotoxic effect when applied to Molt-3, another T
      lymphblastic leukemic cell line. The antiestrogens arrested the cells at
      G(0)/G(1) phase and induced apoptosis. Using the CCRF/VCR(1000) cell line, which
      is resistant to vincristine, it was observed that the effect of nafoxidine on
      modulating drug resistance was manifested at a lower concentration than that
      causing a direct cytotoxic effect. Nafoxidine inhibited the Pgp pump activity as
      measured by rhodamine 123 efflux. Combination with verapamil was found to be more
      effective in abrogating the pump activity. This study points to the
      multifactorial activities of nonsteroidal antiestrogens against lymphoblastic
      leukemia and implies their potential use in clinical treatment as antileukemic
      drugs.

PMID- 14585327
TI  - Comparison of methods for DNA extraction from paraffin-embedded tissues and
      buccal cells.
AB  - Both paraffin-embedded tissue specimens and buccal cells are excellent resources
      for large-scale molecular epidemiological studies. In order to identify the
      optimal method for DNA extraction, we compared three methods: (1) modified phenol
      chloroform protocol; (2) simple boiling method; and (3) DNA Extraction Mini Kit.
      For paraffin-embedded tissue specimens, amplification of the beta-globin gene
      sequence was successful in 30 of 34 (88.2%) by the simple boiling method, 29 of
      34 (85.3%) samples using DNA extracted by the phenol-chloroform method, and 18 of
      34 (52.9%) by the DNA Mini Kit. For buccal cells, amplification of the beta
      globin gene sequence was successful in 16 of 17 (94.1%) DNA samples extracted by
      the phenol-chloroform method, 2 of 16 (12.5%) by the simple boiling method, and
      12 of 16 (75%) by the DNA Mini Kit. Both the simple boiling method and the phenol
      chloroform method are better methods for DNA isolation from paraffin-embedded
      tissue specimens, and the phenol-chloroform method is the best method for DNA
      extraction from buccal cells.

PMID- 14585329
TI  - Are weak protein-protein interactions the general rule in capsid assembly?

PMID- 14585328
TI  - Direct comparison of microarray gene expression profiles between non
      amplification and a modified cDNA amplification procedure applicable for needle
      biopsy tissues.
AB  - Global gene expression profiling by cDNA microarray analysis has been used to
      discover the biomarkers for early diagnosis of various cancers, subclassing
      cancer type, and prediction of patient's treatment outcome. The information
      provided by gene expression profiling may contribute to the design of molecular
      mechanism-based strategies for cancer prevention and/or treatment. However, the
      standard procedure for cDNA microarray analysis requires 5mug of good quality
      total RNA as starting material for each target preparation reaction. Thus, there
      is a limit for needle biopsy samples, laser capture microdissected tissues, or
      flow-sorted cells to successfully utilize the microarray technology. In order to
      profile the gene expression of needle biopsy tissue, we have modified the
      standard protocol by carrying out cDNA amplification after cDNA synthesis. We
      compared percentage present calls, absent calls, reproducibility, and concordance
      in needle biopsy samples processed by standard microarray protocol (cDNA non
      amplification method) and our modified protocol (cDNA amplification method). The
      results showed that cDNA amplification method provided high reproducibility,
      representation, and concordance with the standard cDNA non-amplification method.
      We have successfully analyzed the gene expression profiles of needle biopsy
      tissues using the modified method without significantly changing the expression
      profiles. These results suggest that the global gene expression profiles of small
      biopsy samples can be achieved by our modified method to facilitate the analysis
      of gene expression profiles for clinical application.

PMID- 14585331
TI  - The carboxy-terminal, M3 motifs of PACT and TRBP have opposite effects on PKR
      activity.
AB  - PKR is an interferon(IFN)-induced, serine-threonine protein kinase, which plays a
      crucial role in IFN's antiviral and antiproliferative actions. The three known
      activators of PKR are dsRNA, heparin, and PACT. PACT activates PKR by direct
      protein-protein interaction in response to cellular stress. The human TAR (trans
      activating region)-binding protein (TRBP), which is very homologous to PACT, also
      interacts with PKR, leading to an inhibition of PKR activity. Since these two
      highly homologous proteins have opposite effects on PKR, we examined if they
      interact with PKR differently by assaying their interaction with various point
      mutants of PKR. Our results indicate that TRBP and PACT interact with PKR through
      the same residues, and no differences were identified in these two interactions.
      Domain swap experiments between PACT and TRBP indicated that the inhibitory
      effects of TRBP on PKR activity are mediated through its carboxy-terminal
      residues, which contain TRBP's third dsRNA-binding motif.

PMID- 14585330
TI  - The endogenous langur type D retrovirus PO-1-Lu and its exogenous counterparts in
      macaque and langur monkeys.
AB  - PO-1-Lu, the endogenous type D retrovirus of langurs (Trachypithecus obscurus)
      has previously been considered a progenitor to the prototype type D retrovirus,
      Mason Pfizer monkey virus (M-PMV/SRV-3), that became established in macaque
      monkeys (Macaca spp.) following a zoonosis. This study reevaluates this
      hypothesis to include other exogenous SRVs. New sequence information from the
      gp70(SU)-encoding region of PO-1-Lu shows striking similarity to the newly
      identified exogenous langur retrovirus, SRV-6, recently isolated from the Hanuman
      Langur (Semnopithecus entellus). An unrooted, bootstrapped neighbor-joining tree
      derived from env gene nucleotide sequences shows PO-1-Lu and SRV-6 appear more
      closely related genetically to SRV-2 than SRV-1 or SRV-3 (M-PMV). This is also
      reflected in our observations that the M-PMV envelope glycoprotein precursor
      gPr86(Env) and gp70(SU) were antigenically distinct from PO-1-Lu, although the
      gp22(TM) glycoproteins were antigenically cross-reactive. The potential that SRV
      6 represents an exogenous form of PO-1-Lu that has arisen following a recent
      zoonosis is discussed.

PMID- 14585332
TI  - Mutations in the C3 region of human and simian immunodeficiency virus envelope
      have differential effects on viral infectivity, replication, and CD4-dependency.
AB  - Residues within the highly conserved C3 region of human and simian
      immunodeficiency virus (HIV, SIV) envelope proteins (Envs) bind directly to the
      cellular CD4 receptor. However, substitutions of D385, which is critical for CD4
      engagement along with other changes such as G382R, G383R, frequently arise in SIV
      mac-infected macaques. We investigated the influence of substitutions in the
      SIVmac and HIV-1 C3 regions on viral entry, dependence on CD4, and replication.
      Mutations flanking the C3 region such as G382R or V388A enhanced and changes
      within the C3 region (i.e., G383R or D385N) impaired SIVmac infectivity. Several
      naturally occurring sequence variations in the SIVmac Env C3 region facilitated
      CD4-independent membrane fusion but abrogated viral replication, suggesting that
      efficient infection requires additional changes elsewhere in Env. Substitutions
      of S365R and D368G in the HIV-1 Env, which correspond to G382 and D385 in SIVmac
      Env, consistently impaired viral infectivity. In contrast, mutation of D368N
      resulted in a virus that could not spread in cells expressing low levels of CD4,
      but which replicated efficiently when high levels of CD4 were expressed. Thus,
      changes in the C3 region of HIV-1 or SIVmac Env can have differential effects on
      viral infectivity and CD4-dependency. We conclude that substitutions flanking the
      C3 region in SIVmac Env such as G382R or V388A represent one step toward
      adaptation to growth in target cells expressing low CD4 levels, whereas changes
      within the C3 region that disrupt CD4 binding might indicate the emergence of CD4
      independent variants at later stages of infection, which could potentially
      broaden viral tropism.

PMID- 14585333
TI  - Avian leukosis virus is a versatile eukaryotic platform for polypeptide display.
AB  - Display technology refers to methods of generating libraries of modularly coded
      biomolecules and screening them for particular properties. Retroviruses are good
      candidates to be a eukaryotic viral platform for the display of polypeptides
      synthesized in eukaryotic cells. Here we demonstrate that avian leukosis virus
      (ALV) provides an ideal platform for display of nonviral polyaeptides expressed
      in a eukaryotic cell substrate. Different sizes of polypeptides were genetically
      fused to the extreme N-terminus of the ALV envelope glycoprotein in an ALV
      infectious clone containing an alkaline phosphatase reporter gene. The chimeric
      envelope glycoproteins were efficiently incorporated into virions and were stably
      displayed on the surface of the virions through multiple virus replication
      cycles. The foreign polypeptides did not interfere with the attachment and entry
      functions of the underlying ALV envelope glycoproteins. The displayed
      polypeptides were fully functional and could efficiently mediate attachment of
      the recombinant viruses to their respective cognate receptors. This study
      demonstrates that ALV is an ideal display platform for the generation and
      selection of libraries of polypeptides where there is a need for expression,
      folding, and posttranslational modification in the endoplasmic reticulum of
      eukaryotic cells.

PMID- 14585334
TI  - Epitope selection from an uncensored peptide library displayed on avian leukosis
      virus.
AB  - Phage display libraries have provided an extraordinarily versatile technology to
      facilitate the isolation of peptides, growth factors, single chain antibodies,
      and enzymes with desired binding specificities or enzymatic activities. The
      overall diversity of peptides in phage display libraries can be significantly
      limited by Escherichia coli protein folding and processing machinery, which
      result in sequence censorship. To achieve an optimal diversity of displayed
      eukaryotic peptides, the library should be produced in the endoplasmic reticulum
      of eukaryotic cells using a eukaryotic display platform. In the accompanying
      article, we presented experiments that demonstrate that polypeptides of various
      sizes could be efficiently displayed on the envelope glycoproteins of a
      eukaryotic virus, avian leukosis virus (ALV), and the displayed polypeptides
      could efficiently attach to cognate receptors without interfering with viral
      attachment and entry into susceptible cells. In this study, methods were
      developed to construct a model library of randomized eight amino acid peptides
      using the ALV eukaryotic display platform and screen the library for specific
      epitopes using immobilized antibodies. A virus library with approximately 2 x
      10(6) different members was generated from a plasmid library of approximately 5 x
      10(6) diversity. The sequences of the randomized 24 nucleotide/eight amino acid
      regions of representatives of the plasmid and virus libraries were analyzed. No
      significant sequence censorship was observed in producing the virus display
      library from the plasmid library. Different populations of peptide epitopes were
      selected from the virus library when different monoclonal antibodies were used as
      the target. The results of these two studies clearly demonstrate the potential of
      ALV as a eukaryotic platform for the display and selection of eukaryotic
      polypeptides libraries.

PMID- 14585335
TI  - Microarray analysis of A549 cells infected with rabbitpox virus (RPV): a
      comparison of wild-type RPV and RPV deleted for the host range gene, SPI-1.
AB  - A documented consequence of poxvirus infections is global inhibition of host
      protein synthesis and reduction in mRNA levels. We examined this mRNA decrease by
      infecting A549 cells, derived from a human lung carcinoma, with rabbitpox virus
      (RPV), or RPV deleted for the serine protease inhibitor SPI-1 (RPVDeltaSPI-1),
      which exhibits a growth defect on A549 cells. At various times postinfection,
      mRNA profiles were analyzed using Affymetrix U95AV2 microarrays. There was a
      decline in overall cellular mRNA levels beginning at 2.5 hpi, and by 5 hpi, mRNA
      levels were drastically reduced for the majority of genes. However, several mRNAs
      increased, including those of heat-shock genes. Finally, a comparison of host
      mRNA profiles of RPV- to RPVDeltaSPI-1-infected cells revealed subtle differences
      in mRNA levels at 5 and 12 hpi. In summary, while there was a global decrease of
      host mRNA levels, the induction of selected mRNAs may be required for a
      successful poxvirus infection.

PMID- 14585336
TI  - Direct interferon-gamma-mediated protection caused by a recombinant
      coxsackievirus B3.
AB  - Coxsackievirus B3 (CVB3) is one of the most important causes of viral
      myocarditis. Cytokines are involved in the control of CVB3 replication and
      pathogenesis. Local expression of specific cytokines by recombinant CVB3 confers
      prevention of virus-caused myocarditis. Expression of IFN-gamma by CVB3(IFN
      gamma) protected BALB/c and C57BL/6 mice when the lethal infection with the
      highly pathogenic CVB3H3 variant was given directly after or prior to CVB3(IFN
      gamma) inoculation by decreasing the viral load and spread as well as tissue
      destruction. This direct effect was not restricted to the homologous virus. In
      vitro, cocultivation of CVB3(IFN-gamma)-infected cells induced a reduction of
      CVB3H3 replication and virus-induced cytopathogenicity.

PMID- 14585337
TI  - Needle-free Biojector injection of a dengue virus type 1 DNA vaccine with human
      immunostimulatory sequences and the GM-CSF gene increases immunogenicity and
      protection from virus challenge in Aotus monkeys.
AB  - A dengue-1 DNA vaccine containing sequences encoding premembrane and envelope
      proteins (DIME) was previously shown to elicit virus neutralizing antibodies in
      rhesus and Aotus monkeys, and the primates were partially protected from viremia
      upon challenge. To increase the neutralizing antibody levels and subsequent
      protection from virus challenge, four strategies were evaluated: (a)
      coimmunization with a plasmid expressing Aotus GM-CSF gene; (b) coimmunization
      with a plasmid containing human immunostimulatory sequences (ISS); (c)
      coimmunization with both the GM-CSF gene and ISS; and (d) delivery of vaccine
      using the needle-free Biojector system. Vaccination with the mixed formulation
      containing DIME, GM-CSF gene, and ISS, by either needle injection or Biojector,
      led to neutralizing antibody titers that were stable for up to 6 months after
      vaccination. Furthermore, 6 of 7 monkeys (85%), and 7 of 8 monkeys (87%)
      receiving this formulation were completely protected from viremia when challenged
      1 and 6 months after vaccination, respectively. This is a significant improvement
      compared to our previous study in which one of three monkeys (33%) receiving just
      the DIME vaccine was completely protected from viremia at 6 months after
      immunization.

PMID- 14585338
TI  - Functional analysis of the human cytomegalovirus immune evasion protein,
      pUS3(22kDa).
AB  - Human cytomegalovirus (HCMV) is an important opportunistic pathogen that
      infrequently causes disease in individuals with mature immune systems. The HCMV
      US3 gene encodes a 22-kDa protein that interferes with immune recognition of
      virally infected cells. The 22-kDa US3 protein binds to major histocompatibility
      complex (MHC) class I complexes, retaining them in the endoplasmic reticulum
      (ER), thereby decreasing the presentation of viral antigen to cytotoxic T cells.
      Our studies demonstrate that correct folding of the ER lumenal domain of the US3
      protein is essential, but insufficient for interactions with MHC class I
      complexes. We demonstrate a requirement for the transmembrane domain of the 22
      kDa US3 protein, confirming the results of others, and also show that the
      cytosolic carboxyl-terminal tail influences the function of the protein.
      Anchoring of the ER-lumenal immunoglobulin-like fold of the US3 protein to the
      membrane of the endoplasmic reticulum is critical for the binding and retention
      of MHC class I complexes.

PMID- 14585339
TI  - A novel monoclonal antibody specific to the C-terminal tail of the gp41 envelope
      transmembrane protein of human immunodeficiency virus type 1 that preferentially
      neutralizes virus after it has attached to the target cell and inhibits the
      production of infectious progeny.
AB  - SAR1 is a new IgG2a murine monoclonal antibody derived by immunization with a
      plant virus expressing the sequence GERDRDR from the C-terminal tail of the gp41
      transmembrane glycoprotein of human immunodeficiency virus type 1 (HIV-1). SAR1
      binds to peptides and proteins carrying the GERDRDR sequence, to some but not all
      preparations of purified virus, and to cells infected with all viruses tested. In
      a standard neutralization assay, SAR1 failed to neutralize, or neutralized
      poorly, a number of T cell line-adapted viruses. However, it was more effective
      at postattachment neutralization. This was measured by two assays, the inhibition
      of the syncytium production by input virus, and the inhibition of the production
      of infectious progeny virus. In general SAR1 was more effective at neutralizing
      progeny virus than inoculum virus. Fifty percent inhibition of progeny virus
      production by different HIV-1 strains was obtained with 2-26 microg/ml of SAR1.
      The SAR1 neutralizing epitope was mapped specifically to the gp41 C-terminal
      tail. SAR1 is an unusual, if not unique, antibody whose activity supports the
      view that part of the gp41 C-terminal tail is exposed on the outside of the
      virion.

PMID- 14585340
TI  - A novel type of VP4 carried by a porcine rotavirus strain.
AB  - The gene encoding the VP8* trypsin-cleavage product of the VP4 protein of porcine
      rotavirus strain A34 was sequenced, and the predicted amino acid (aa) sequence
      was compared to the homologous region of all known P genotypes. The aa sequence
      of the VP8* of strain A34 shared low identity, ranging from 39% (bovine strain
      B223, P8[11]) to 76% (human strain 69M, P4[10]), with the homologous sequences of
      representative strains of the remaining 21 P genotypes. Phylogenetic
      relationships showed that the VP8* of strain A34 shares a common evolutionary
      lineage with those of human 69M (P4[10]) and equine H-2 (P4[12]) strains.
      Hyperimmune sera raised to strain A34 and to a genetic reassortant strain
      containing the VP4 gene from strain A34, both with high homologous neutralization
      titer via VP4, failed to neutralize strains representative of 15 different P
      genotypes. These results indicate that strain A34 should be considered as
      prototype of a new P genotype and serotype (P14[23]) and provide further evidence
      for the vast genetic and antigenic diversity of group A rotaviruses.

PMID- 14585341
TI  - Evolutionary relationship between Old World West Nile virus strains. Evidence for
      viral gene flow between Africa, the Middle East, and Europe.
AB  - Little is known about the genetic relationships between European and other Old
      World strains of West Nile virus (WNV) and persistence of WNV North of
      Mediterranean. We characterized the complete genomes of three WNV strains from
      France (horse-2000), Tunisia (human-1997) and Kenya (mosquito-1998), and the
      envelope, NS3 and NS5 genes of the Koutango virus. Phylogenetic analyses
      including all available full-length sequences showed that: (1) Koutango virus is
      a distant variant of WNV; (2) the three characterized strains belong to lineage
      1, clade 1a; (3) the Tunisian strain roots the lineage of viruses introduced in
      North America. We established that currently available partial envelope sequences
      do not generate reliable phylogenies. Accordingly, establishing a large WNV
      sequence database is pivotal for the understanding of spatial and temporal
      epidemiology of this virus. For rapid completion of that purpose, colinearized E
      NS3-NS5 gene sequences were shown to constitute a valuable surrogate for complete
      sequences.

PMID- 14585343
TI  - EBNA1 efficiently assembles on chromatin containing the Epstein-Barr virus latent
      origin of replication.
AB  - The Epstein-Barr virus (EBV) protein, EBNA1, activates the replication of latent
      EBV episomes and the transcription of EBV latency genes by binding to recognition
      sites in the DS and FR elements of oriP. Since EBV episomes exist as chromatin,
      we have examined the interaction of EBNA1 with oriP templates assembled with
      physiologically spaced nucleosomes. We show that EBNA1 retains the ability to
      efficiently bind its recognition sites within the DS and FR elements in oriP
      chromatin and that this property is intrinsic to the EBNA1 DNA binding domain.
      The efficient assembly of EBNA1 on oriP chromatin does not require ATP-dependent
      chromatin remodeling factors and does not cause the precise positioning of
      nucleosomes within or adjacent to the FR and DS elements. Thus EBNA1 belongs to a
      select group of proteins that can efficiently access their recognition sites
      within nucleosomes without the need for additional chromatin remodeling factors.

PMID- 14585342
TI  - The C protein of measles virus inhibits the type I interferon response.
AB  - Type I interferons (IFNalpha/beta) are an important part of innate immunity to
      viral infections because they induce an antiviral response and limit viral
      replication until the adaptive response clears the infection. Since the
      nonstructural proteins of several paramyxoviruses inhibit the IFNalpha/beta
      response, we chose to explore the role of the C protein of measles virus (MV) in
      such inhibition. Previous studies have suggested that the MV C protein may serve
      as a virulence factor, but its role in the pathogenesis of MV remains undefined.
      In the present study, a recombinant MV strain that does not express the C protein
      (MV C-) and its parental strain (Ed Tag) were used. Growth of MV C- was
      restricted in human peripheral blood mononuclear cells and HeLa cells, but in the
      presence of neutralizing antibodies to IFNalpha/beta, MV C- produced titers that
      were equivalent to those of Ed Tag. In addition, expression of the MV C protein
      from plasmid DNA inhibited the production of an IFNalpha/beta responsive reporter
      gene and, to a lesser extent, inhibited an IFNgamma responsive reporter gene. The
      ability of the MV C protein to suppress the IFNalpha/beta response was confirmed
      using a biologic assay. After IFNbeta stimulation, HeLa cells infected with Ed
      Tag produced five-fold less IFNalpha/beta than cells infected with MV C-. While
      the mechanism of inhibition remains unclear, these data suggest that the MV C
      protein plays an important role in the pathogenesis of MV by inhibiting
      IFNalpha/beta signaling.

PMID- 14585344
TI  - High throughput testing of the SV40 Large T antigen binding to cellular p53
      identifies putative drugs for the treatment of SV40-related cancers.
AB  - SV40 has been linked to some human malignancies, and the evidence that this virus
      plays a causative role in mesothelioma and brain tumors is mounting. The major
      SV40 oncoprotein is the Large tumor antigen (Tag). A key Tag transforming
      activity is connected to its capability to bind and inactivate cellular p53. In
      this study we developed an effective, high throughput, ELISA-based method to
      study Tag-p53 interaction in vitro. This assay allowed us to screen a chemical
      library and to identify a chemical inhibitor of the Tag binding to p53. We
      propose that our in vitro assay is a useful method to identify molecules that may
      be used as therapeutic agents for the treatment of SV40-related human cancers.

PMID- 14585345
TI  - Functional analysis of the cloverleaf-like structure in the 3' untranslated
      region of bamboo mosaic potexvirus RNA revealed dual roles in viral RNA
      replication and long distance movement.
AB  - The 3' untranslated region (UTR) of bamboo mosaic potexvirus (BaMV) RNA was
      identified to fold into a tertiary structure comprising a cloverleaf-like
      structure designated ABC domain followed by a major stem-loop D, which in turn is
      followed by a pseudoknot E and a poly(A) tail. The coat protein accumulation
      level of the mutant, BaMV40A/DeltaABC, lacking ABC domain was just 15% that of
      wild-type when inoculated into protoplasts of Nicotiana benthamiana. This
      suggested that ABC domain might play an important role in BaMV RNA replication.
      To define the precise role of each of the three stem-loops of ABC domain in RNA
      replication, three mutants BaMV40A/DeltaA, -/DeltaB, and -/DeltaC each lacking
      stem-loop A, B, and C, respectively, were created. Our results showed that
      accumulation of viral products of mutants BaMV40A/DeltaB and -/DeltaC were not as
      efficient as wild-type. On the contrary, level of accumulation of viral products
      of BaMV/DeltaA was similar to that of wild-type in protoplasts and inoculated
      leaves. Interestingly, the accumulation of viral products was not as efficient as
      that of wild-type in systemic leaves, implying that stem-loop A is dispensable
      for replication, but signifies a role in systemic accumulation. Using UV cross
      linking and competition experiments, it was demonstrated that the E. coli
      expressed helicase domain of BaMV ORF1 can preferentially interact with the ABC
      domain.

PMID- 14585346
TI  - Immunogenicity in pig-tailed macaques of poliovirus replicons expressing HIV-1
      and SIV antigens and protection against SHIV-89.6P disease.
AB  - In the search for an effective vaccine against the human immunodeficiency virus
      (HIV), novel ways to deliver viral antigens are being evaluated. One such
      approach is the use of nonreplicating viral vectors encoding HIV and/or SIV genes
      that are expressed after infection of host cells. Nonreplicating poliovirus
      vectors, termed replicons, that expressed HIV-1/HXB2 and SIVmac239 gag and
      various HIV-1 env genes from different clades were tested for immunogenicity and
      protective efficacy against intravenous challenge of pig-tailed macaques with
      SHIV-89.6P. To maximize both cellular and humoral immune responses, a prime-boost
      regimen was used. Initially, macaques were immunized four times over 35 weeks by
      either the intranasal and intrarectal or the intramuscular (im) route with
      mixtures of poliovirus replicons expressing HIV-1 gag and multiple env genes.
      Immunization with replicons alone induced both serum antibodies and lymphocyte
      proliferative responses. After boosting with purified Env protein, neutralizing
      antibodies to SHIV-89.6P were induced in four of five immunized animals. In a
      second experiment, four macaques were immunized im three times over 27 weeks with
      replicons expressing the SIVmac239 gag and HIV-1/HXB2 env genes. All immunized
      animals were then boosted twice with purified HIV-1-89.6 rgp140-Env and SIVmac239
      p55-Gag proteins. Four control animals received only the two protein
      inoculations. Immunized and control animals were then challenged intravenously
      with the pathogenic SHIV-89.6P. After challenge the animals were monitored for
      virus isolation from peripheral blood mononuclear cells and plasma viremia and
      for changes in virus-specific antibody titers. Naive pig-tailed macaques
      experienced rapid loss of CD4(+) T cells and died between 38 and 62 weeks after
      infection. In contrast, macaques immunized with replicons and proteins rapidly
      cleared plasma virus and did not experience sustained loss of CD4(+) lymphocytes.
      Furthermore, two of the four macaques that were immunized only with purified
      proteins maintained high viral burdens and lost greater than 95% of their CD4(+)
      lymphocytes within 2 to 4 weeks after challenge. Thus, poliovirus replicons
      expressing HIV-1 and SIV antigens were immunogenic in pig-tailed macaques and
      appeared to enhance the protective effects observed after administration of
      purified proteins alone.

PMID- 14585348
TI  - Vesicular stomatitis virus: an exciting new therapeutic oncolytic virus candidate
      for cancer or just another chapter from Field's Virology?
AB  - Selected mutant strains of vesicular stomatitis virus (VSV) are described that
      are unable to combat endogenous IFN-beta signaling within infected normal cells
      and as a result are dramatically more selective for productive growth in tumor
      cells having a defective antiviral response. The VSV mutants may have the
      potential to be used clinically as a systemic oncolytic agent for the treatment
      of distal and metastatic cancers.

PMID- 14585349
TI  - Signal transduction: putting translation before transcription.
AB  - A recent microarray-based study shows that Ras/Akt signaling rapidly alters the
      pattern of existing mRNAs that are recruited to polysomes. This response precedes
      the effects of transcription on total cellular RNA, suggesting that the primary
      effect of Ras/Akt signaling on gene expression may occur mainly at the level of
      translation.

PMID- 14585350
TI  - Developmental biology informs cancer: the emerging role of the hedgehog signaling
      pathway in upper gastrointestinal cancers.
AB  - The hedgehog (Hh) signaling pathway plays many roles in invertebrate and
      vertebrate development. For example, specific inhibition of sonic Hh expression
      is critical during early stages of pancreas organogenesis, but an active Hh
      pathway appears to be required for maintenance of adult endocrine functions.
      Mutational inactivation of the Hh pathway has been demonstrated in human
      malignancies of the skin, cerebellum, and skeletal muscle. Now, two papers
      implicate aberrant Hh signaling in human upper gastrointestinal cancers including
      those developing from the esophagus, stomach, biliary tract, and pancreas.

PMID- 14585351
TI  - No PUMA, no death: implications for p53-dependent apoptosis.
AB  - More than a decade ago, it was found that one of the two essential physiological
      functions of p53 is to selectively destroy stressed cells through apoptosis.
      Despite the large number of studies describing p53-dependent apoptosis since
      then, how p53 turns on the apoptotic switch has remained enigmatic. In this issue
      of Cancer Cell, Jeffers et al. report that knockout of PUMA, a recently
      identified BH3-only Bcl-2 family protein, recapitulates virtually all apoptotic
      deficiency in p53 knockout mice. Their results indicate that PUMA is an essential
      mediator of p53-dependent and -independent apoptosis in vivo.

PMID- 14585352
TI  - When protein destruction runs amok, malignancy is on the loose.
AB  - Ubiquitin-dependent proteolysis ensures that specific protein functions are
      turned off at the right time, in the right place, and in a unidirectional
      fashion. The high substrate specificity of the system is determined by a large
      family of ubiquitin ligases, which competes with the protein kinases to be the
      largest family of enzymes in mammals. Given the crucial function of the
      proteolytic machinery, altered degradation of cellular regulators contributes to
      the unchecked proliferation typical of cancer cells. Here we review the aberrant
      activity of a variety of ubiquitin ligases in human cancer, hence the prospect of
      targeting them in cancer therapy.

PMID- 14585353
TI  - Targeting the PI3K-Akt pathway in human cancer: rationale and promise.

PMID- 14585354
TI  - VSV strains with defects in their ability to shutdown innate immunity are potent
      systemic anti-cancer agents.
AB  - Ideally, an oncolytic virus will replicate preferentially in malignant cells,
      have the ability to treat disseminated metastases, and ultimately be cleared by
      the patient. Here we present evidence that the attenuated vesicular stomatitis
      strains, AV1 and AV2, embody all of these traits. We uncover the mechanism by
      which these mutants are selectively attenuated in interferon-responsive cells
      while remaining highly lytic in 80% of human tumor cell lines tested. AV1 and AV2
      were tested in a xenograft model of human ovarian cancer and in an immune
      competent mouse model of metastatic colon cancer. While highly attenuated for
      growth in normal mice, both AV1 and AV2 effected complete and durable cures in
      the majority of treated animals when delivered systemically.

PMID- 14585356
TI  - Disruption of Id1 reveals major differences in angiogenesis between transplanted
      and autochthonous tumors.
AB  - Id genes regulate tumor angiogenesis and loss of Id1 inhibits tumor xenograft
      growth in mice. Here we evaluate the role of Id1 in a more clinically relevant
      tumor model system using a two-step chemical carcinogenesis protocol. Remarkably,
      we find that Id1-/- mice are more susceptible to skin tumorigenesis compared to
      their wild-type counterparts. Cutaneous neoplasms in Id1-/- mice show increased
      proliferation without alterations in tumor angiogenesis; however, Id1-/- mice
      possess 50% fewer cutaneous gammadelta T cells than their wild-type counterparts
      due to an intrinsic migration defect associated with loss of expression of the
      chemokine receptor, CXCR4. We suggest that there are important differences
      between the mechanisms of angiogenesis in transplanted and autochthonous tumors
      and that these findings will have significant implications for the potential
      utility of antiangiogenic therapies in cancer.

PMID- 14585355
TI  - Effect of angiogenesis inhibition by Id loss and the contribution of bone-marrow
      derived endothelial cells in spontaneous murine tumors.
AB  - Angiogenic defects in Id mutant mice inhibit the growth of tumor xenografts,
      providing a genetic model for antiangiogenic stress. Our work tests the
      consequences of such stress on progression of more physiological Pten+/- tumors.
      While tumor growth occurs despite impaired angiogenesis, disruption of
      vasculature by Id loss causes tumor cells to experience hypoxia and necrosis, the
      extent of which is tumor dependent. We show that bone-marrow-derived endothelial
      precursors contribute functionally to neovasculature of some but not all Pten+/-
      tumors, partially rescuing Id mutant phenotype. We demonstrate that loss of Id1
      in tumor endothelial cells results in downregulation of several proangiogenic
      genes, including alpha6 and beta4 integrins, matrix metalloprotease-2, and
      fibroblast growth factor receptor-1. Inhibition of these factors phenocopies loss
      of Id in in vivo angiogenesis assays.

PMID- 14585357
TI  - Tumor suppressor p16INK4a determines sensitivity of human cells to transformation
      by cooperating cellular oncogenes.
AB  - The Ink4a/Arf locus encodes two distinct proteins, both of which may contribute
      to senescence and tumor suppression. We find that human diploid fibroblasts
      (HDFs) that are specifically deficient for p16INK4a achieve anchorage
      independence when transduced with retroviruses encoding telomerase (hTERT) and
      either Ras or Myc. Significantly, Ras and Myc together enable the cells to form
      tumors in nude mice but at a frequency that suggests additional genetic changes.
      All five tumors analyzed expressed high levels of Ras and retained functional
      p53, although two showed downregulation of Arf. Cytogenetic analyses identified
      clonal chromosomal alterations that may have contributed to tumorigenesis, but
      the tumor cells were essentially diploid.

PMID- 14585358
TI  - The tumor-suppressive functions of the human INK4A locus.
AB  - The INK4A locus is often inactivated in human cancer. INK4A encodes for p14ARF
      and p16INK4A that inhibit growth through p53 and pRb, respectively. We used RNA
      interference vectors in transformation assays of human primary cells to analyze
      tumor-suppressive functions. We first show that a concerted inactivation of pRb
      and p53 is required for transformation. We then demonstrate that loss of p14ARF
      enhances growth in a p53-dependent manner but has little tumorigenic effect. In
      contrast, suppression of p16INK4A expression does not affect cellular
      proliferation but synergizes with p53 loss to accelerate growth and cause
      transformation. Our results delineate the functions of the human INK4A genes in
      normal and tumorigenic growth.

PMID- 14585359
TI  - Puma is an essential mediator of p53-dependent and -independent apoptotic
      pathways.
AB  - Puma encodes a BH3-only protein that is induced by the p53 tumor suppressor and
      other apoptotic stimuli. To assess its physiological role in apoptosis, we
      generated Puma knockout mice by gene targeting. Here we report that Puma is
      essential for hematopoietic cell death triggered by ionizing radiation (IR),
      deregulated c-Myc expression, and cytokine withdrawal. Puma is also required for
      IR-induced death throughout the developing nervous system and accounts for nearly
      all of the apoptotic activity attributed to p53 under these conditions. These
      findings establish Puma as a principal mediator of cell death in response to
      diverse apoptotic signals, implicating Puma as a likely tumor suppressor.

PMID- 14585360
TI  - Converging roads: evidence for an adult hemangioblast.
AB  - Classical studies of the developing embryo first suggested the existence of the
      hemangioblast, a precursor cell with the potential to differentiate into both
      blood and blood vessels. Several lines of investigation demonstrated that many of
      the genes activated during early hematopoietic development are also expressed in
      the vascular endothelium. Gene-targeting studies using embryonic stem cells have
      identified Flk-1, SCL, and Runx-1 as important regulatory molecules that specify
      both hematopoietic and vascular outcomes. Although it was anticipated that the
      hemangioblast would be present only during the earliest stages of vascular
      development in the yolk sac, accumulating evidence now indicates that
      hematopoietic cells with hemangioblast activity persist into adulthood. In the
      adult, bone marrow-derived, circulating endothelial progenitors contribute to
      postnatal neovascularization and enhance vascular repair following ischemic
      injury. Highly purified populations of hematopoietic stem cells from humans and
      mice can differentiate into both blood cells and vascular tissue at the single
      cell level. These recent findings suggest that bone marrow-derived hematopoietic
      stem cells or their progeny may contribute to the maintenance and repair of both
      the hematopoietic and the vascular systems during adult life.

PMID- 14585361
TI  - Hematopoiesis from embryonic stem cells: lessons from and for ontogeny.
AB  - Cellular therapies derived from embryonic stem (ES) cells have acquired new
      interest and urgency with the demonstration that embryonic stem cells can be
      established from human blastocyst-stage embryos. Our ability to derive
      therapeutic cells from differentiating ES cell cultures will ultimately depend on
      our understanding of the embryonic developmental processes that direct the
      differentiation of pluripotent cells into transplantable lineage-specific stem
      cells, and on our ability to recapitulate these processes in vitro. In this
      review, we evaluate the work that has been done to date on the hematopoietic
      differentiation of ES cells, and discuss this in the context of what is known
      about the embryonic origin of the hematopoietic stem cell.

PMID- 14585362
TI  - Retrovirus-mediated gene transfer and expression cloning: powerful tools in
      functional genomics.
AB  - Most of the human genome has now been sequenced and about 30,000 potential open
      reading frames have been identified, indicating that we use these 30,000 genes to
      functionally organize our biologic activities. However, functions of many genes
      are still unknown despite intensive efforts using bioinformatics as well as
      transgenic and knockout mice. Retrovirus-mediated gene transfer is a powerful
      tool that can be used to understand gene functions. We have developed a variety
      of retrovirus vectors and efficient packaging cell lines that have facilitated
      the development of efficient functional expression cloning methods. In this
      review, we describe retrovirus-mediated strategies used for investigation of gene
      functions and function-based screening strategies.

PMID- 14585363
TI  - Slow receptor acquisition by NK cells regenerated in vivo from transplanted fetal
      liver or adult bone marrow stem cells.
AB  - Adult mouse natural killer (NK) cells express two families of MHC class I
      specific receptors, namely Ly49 and CD94/NKG2, whereas fetal and neonatal NK
      cells express only CD94/NKG2. After birth, Ly49(+) NK cells slowly increase and
      CD94/NKG2(+) NK cells decrease. The aim of this study was to determine whether
      murine NK cells develop differently from transplants of fetal liver and adult
      marrow stem cells and whether the adult marrow microenvironment is critical for
      NK receptor maturation. Enriched populations of stem cells were transplanted into
      adult mice, and the kinetics of NK receptor acquisition was examined. NK cells
      from osteopetrotic Csf1(op)/Csf1(op) mice, in which hematopoiesis within the
      marrow is severely limited, were also analyzed.NK cells regenerated from both
      fetal and adult stem cells initially resembled neonatal NK cells in their slow
      acquisition of Ly49 over several weeks, although the adult stem cell-derived NK
      cells matured approximately 10 days sooner. NK cells from adult Csf1(op)/Csf1(op)
      mice expressed normal levels of Ly49. Maturation of the NK receptor repertoire is
      a slow process regardless of their stem cell origin or reduced marrow space
      caused by osteopetrosis.

PMID- 14585364
TI  - Humanized anti-CD25 monoclonal antibody for prophylaxis of graft-vs-host disease
      (GVHD) in haploidentical bone marrow transplantation without ex vivo T-cell
      depletion.
AB  - OBJECTIVE: To investigate the effects of a novel anti-IL-2 receptor (CD25)
      monoclonal antibody, basiliximab, on graft-vs-host disease (GVHD) and engraftment
      in haploidentical bone marrow transplantation (BMT). MATERIALS AND METHODS:
      Thirteen consecutive high-risk leukemia patients (age 9-41) underwent
      haploidentical BMT with G-CSF-primed marrow as stem cells without ex vivo T-cell
      depletion. Basiliximab, along with a combination of cyclosporine (CSA),
      methotrexate (MTX), and mycophenolate mofetil (MMF), was used for GVHD
      prophylaxis. Immunophenotyping, limited-dilution assay, and colony-forming assays
      were used to measure the effect of basiliximab on the subsets of lymphocytes,
      cytotoxic T-lymphocyte precursors (CTLp), and hematopoietic cells. RESULTS: All
      patients established successful trilineage engraftment with full donor chimerism.
      No patients developed grade II-IV acute GVHD. Patients who survived more than 12
      months and were free of relapse showed limited chronic skin GVHD. Ten of 13
      patients are currently alive with a Karnofsky performance score of 100% at median
      follow-up of 17 months (range 12-24 months). Basiliximab significantly decreased
      alloreactive CTLp by 10-fold to 100-fold in limiting-dilution assays. It had no
      effect on hematopoietic stem and progenitor cells as determined by in vitro
      colony-forming assays. CONCLUSION: The addition of basiliximab to CSA, MMF, and
      MTX as GVHD prophylaxis effectively reduced severe lethal GVHD in haploidentical
      BMT. It is possible to selectively eliminate or reduce the number of alloreactive
      T cells with anti-CD25 antibody, which results in prevention of or a reduction in
      the severity of GVHD.

PMID- 14585365
TI  - Antithymocyteglobulin as prophylaxis of graft failure and graft-versus-host
      disease in recipients of partially T-cell-depleted grafts from matched unrelated
      donors: a dose-finding study.
AB  - OBJECTIVE: In this study, we set out to evaluate the effect of three different
      antithymocyteglobulin (ATG) doses on graft failure and incidence of graft-vs-host
      disease (GVHD) among recipients of partially T-cell-depleted (TCD) grafts from
      matched unrelated donors (MUDs). PATIENTS AND METHODS: Data of 74 consecutively
      treated MUD recipients were analyzed. Fifty-two, 13, and 9 MUD patients were
      treated with ATG in a total dose of 8 mg/kg, 6 mg/kg, and 4 mg/kg (given from
      days -8 until -4), respectively. RESULTS: Granulocyte and platelet engraftment
      were not different between the groups, while graft failure was observed in two
      patients only (receiving 8 mg/kg and 4 mg/kg ATG, respectively). The cumulative
      incidence of severe (grade III-IV) acute GVHD and extensive chronic GVHD was 4%,
      0%, 44% and 11%, 8%, 44% in groups receiving ATG in a dose of 8 mg/kg, 6 mg/kg,
      and 4 mg/kg, respectively (severe acute GVHD: p<0.001; extensive chronic GVHD:
      p=0.05). CONCLUSION: Based on these findings, we recommend when ATG is used in
      the setting of stem cell transplantation with (partially) TCD grafts from MUDs,
      to give a total dose of 6 to 8 mg/kg. A further decrease in dosage resulted in a
      highly significant increased incidence of severe acute and extensive chronic
      GVHD.

PMID- 14585366
TI  - Generation and ex vivo expansion of cytotoxic T lymphocytes directed toward
      different types of leukemia or myelodysplastic cells using both HLA-matched and
      partially matched donors.
AB  - OBJECTIVE: Successful priming and in vitro expansion of anti-leukemia cytotoxic T
      lymphocytes (CTL) are preliminary conditions for designing approaches of adoptive
      immunotherapy in patients with hematological malignancies undergoing allogeneic
      hematopoietic stem cell transplantation (HSCT). In this study, we evaluated the
      possibility of generating and expanding in vitro CTL directed toward different
      types of either leukemia or myelodysplastic cells, using both HLA-matched and
      partially matched donors. PATIENTS AND METHODS: Eleven donor/recipient pairs were
      enrolled; donor-derived dendritic cells, pulsed with patient blast cells, were
      used to generate CTL. RESULTS: Anti-leukemia CTL lines were successfully obtained
      from 10 of 11 donors. After repeated rounds of stimulation, CTL lines showed,
      along with an increase in cytotoxic activity, a variable but continuous expansion
      of cultured cells. In order to increase the magnitude of CTL expansion, two anti
      leukemia CTL lines were further stimulated using allogeneic feeder cells, anti
      CD3, and low doses of interleukin-2 (IL-2). This stimulation gave rise to 150
      fold to 270-fold expansion of the absolute number of cultured cells. Most
      cultures showed either absent or low reactivity of anti-leukemia CTL against
      patient non-leukemia cells. Three anti-leukemia CTL lines displayed a more
      pronounced cytotoxicity against nonmalignant recipient cells, which was always
      lower than that observed against leukemia blasts (LB). Spectratyping analysis of
      the TCR-Vbeta subfamilies revealed a preferential expansion of oligoclonal
      populations that persisted in CTL lines following repeated rounds of stimulation.
      CONCLUSIONS: Results provide the biological background for designing protocols of
      adoptive immunotherapy for the control of minimal residual disease in patients
      with hematological malignancies given HSCT.

PMID- 14585367
TI  - Strategies to reduce transplant-related mortality after allogeneic stem cell
      transplantation in elderly patients: Comparison of reduced-intensity conditioning
      and unmanipulated peripheral blood stem cells vs a myeloablative regimen and
      CD34+ cell selection.
AB  - OBJECTIVES: The aim of this study was to compare two approaches used to reduce
      transplant-related mortality (TRM) after allogeneic peripheral blood stem cell
      transplantation (allo-PBSCT) in elderly patients. PATIENTS AND METHODS: Data from
      50 patients, 45 years of age or older, consecutively treated with an HLA
      identical sibling allo-PBSCT at the Hospital de Sant Pau were analyzed. We have
      compared the outcome of patients treated with conventional myeloablative regimens
      and CD34(+)-selected cells (CD34(+) group; n=23) with those receiving reduced
      intensity conditioning regimens, consisting of fludarabine (150 mg/m(2)) plus an
      alkylating agent, followed by unmanipulated grafts (RIC group; n=27). Patient
      characteristics were well balanced between the two groups, although patients in
      the RIC group were slightly older. RESULTS: The incidence of acute graft-vs-host
      disease (GVHD) was similar in both groups. The 1-year cumulative incidence of
      extensive chronic GVHD was 38% in the RIC group and 17% in the CD34(+) group
      (p=0.2). After a median follow-up of 28 months, there were no differences in the
      relapse rate. Patients in the RIC group had a lower TRM, with a cumulative
      incidence of 7% vs 30% at 6 months and 15% vs 39% at 1 year (p=0.05). The Kaplan
      Meier estimates of PFS at 2 years was 67% in the RIC group and 43% in the CD34(+)
      group (p=0.09) and the OS was 69% vs 43% (p=0.05), respectively. CONCLUSION:
      CD34(+) cell selection reduced the risk of extensive cGVHD but was associated
      with a higher TRM. Although the number of patients is limited, our study suggests
      that this approach should be restricted to relatively young patients, as better
      outcomes can be achieved in elderly patients using RIC strategies.

PMID- 14585368
TI  - Serum cytokine levels and acute graft-versus-host disease after HLA-identical
      hematopoietic stem cell transplantation.
AB  - OBJECTIVE: The aim of this study was to investigate whether the serum levels of
      soluble interleukin-2R (sIL-2R), tumor necrosis factor-alpha (TNF-alpha),
      interferon-gamma (IFN-gamma), IL-6, IL-10, and transforming growth factor-beta(1)
      (TGF-beta(1)) were associated with the development of acute graft-vs-host disease
      (aGVHD). PATIENTS AND METHODS: Serum cytokine levels were sequentially measured
      by sandwich enzyme-linked immunosorbent assay in 13 patients who had received
      full-match allogeneic hematopoietic stem cell transplantation (HSCT). RESULTS:
      Serum sIL-2R and IL-10 levels from the 1st to the 15th week post transplantation
      were significantly higher in the group that developed aGVHD than in the group
      without aGVHD. sIL-2R levels increased in direct correlation to engraftment and
      at onset of aGVHD, whereas IL-10 levels increased transiently following HSCT. The
      mean TNF-alpha concentration in the first weeks after transplantation was
      augmented in the group that developed aGVHD. Furthermore, a decrease in TGF
      beta(1) levels after engraftment was significantly associated with aGVHD. No
      correlation was found between aGVHD and the other cytokines. CONCLUSIONS: These
      results support the idea that a balance between cytokines derived from type 1 and
      type 2 T-helper cells may be important in the development and control of aGVHD.
      Although sIL-2R, TNF-alpha, IL-10, and TGF-beta(1) levels have been correlated
      with aGVHD, sIL-2R levels at engraftment may provide a better parameter for early
      detection of aGVHD after allogeneic HSCT.

PMID- 14585369
TI  - BAALC, a novel marker of human hematopoietic progenitor cells.
AB  - OBJECTIVE: The gene BAALC (Brain And Acute Leukemia, Cytoplasmic), a novel
      molecular marker involved in leukemia, is highly expressed in a subset of
      patients with acute leukemia and predictive of clinical outcome in patients with
      acute myeloid leukemia and normal karyotype. The role of BAALC in hematopoiesis
      and leukemogenesis is unknown. MATERIAL AND METHODS: We used real-time RT-PCR to
      show that BAALC is strongly expressed in CD34(+) cells from the bone marrow and
      blood and only weakly expressed in total normal bone marrow and blood cells.
      RESULTS: Expression analyses of FACSorted cells revealed high BAALC transcript
      levels in CD34(+) bone marrow cells including CD34(+)/CD38(-), CD34(+)/CD33(+),
      as well as CD34(+)/CD19(+)/CD10(+), CD34(+)/CD7(+), and CD34(+)/CD71(+)/CD45(-)
      cell fractions. Expression was significantly lower in all CD34(-) fractions. In
      vitro differentiation of CD34(+) bone marrow cells showed downregulation of BAALC
      and CD34 transcripts as early as day 4 in suspension cultures supplemented with
      lineage-specific cytokines (G-CSF, M-CSF, or EPO). In cultures with only lineage
      unspecific cytokines (IL-3, SCF, GM-CSF), BAALC transcripts persisted up to day
      20, while CD34 transcripts disappeared earlier. These observations suggest that
      expression of BAALC is stage specific. CONCLUSIONS: BAALC expression is
      restricted to progenitor cells, and downregulation of BAALC occurs with cell
      differentiation. We postulate that BAALC represents a novel marker of an early
      progenitor cell common to the myeloid, lymphoid, and erythroid pathways.

PMID- 14585370
TI  - Selectins and anti-CD15 (Lewis x/a) antibodies transmit activation signals in
      Hodgkin's lymphoma-derived cell lines.
AB  - OBJECTIVE: The CD15 (Lewis x) cell surface oligosaccharide moiety is expressed in
      a variety of normal and tumor cells and recognized by selectins. The detection of
      CD15 on malignant Hodgkin-Reed-Sternberg (HRS) cells serves as a diagnostic
      marker of Hodgkin's lymphoma (HL). Retrospective studies suggest that the
      expression of nonsialylated CD15 molecules on HRS cells has a positive prognostic
      value while presence of sialylated CD15 may correlate with a poor outcome.
      However, the relevance of the CD15 antigen expression to the pathobiology of the
      disease is not clear. In this work, we studied the contribution of CD15 to cell
      adhesion and the activation of signaling cascades in two HL-derived cell lines,
      KMH-2 and L428. METHODS: Immobilized anti-CD15 monoclonal antibodies and
      recombinant E- and P-selectins were used to activate KMH-2 and L428 cells.
      Immunoblotting, immunoprecipitation, and the electrophoretic mobility shift assay
      were performed to detect tyrosine phosphorylation of c-Cbl, c-Jun nuclear
      translocation, and AP-1 DNA binding. RESULTS: Treatment of cells with antibodies
      against the sialylated and nonsialylated forms of CD15, or with immobilized
      selectins, induced changes in cell morphology. Tyrosine phosphorylation of c-Cbl,
      together with tyrosine phosphorylation of multiple protein substrates, was also
      induced. In addition, binding of the CD15 molecules induced nuclear translocation
      of c-Jun and an increase in AP-1 DNA binding activity. CONCLUSIONS: We suggest
      that CD15 has a dual physiological role, both as an adhesion molecule recognized
      by selectins and as a regulatory molecule upstream to specific intracellular
      signaling cascades with implications to the pathogenesis of HL.

PMID- 14585371
TI  - Low expression of MDS1-EVI1-like-1 (MEL1) and EVI1-like-1 (EL1) genes in
      favorable-risk acute myeloid leukemia.
AB  - OBJECTIVE: The expression of an MDS1-EVI1-like-1 (MEL1) gene is reported in acute
      myeloid leukemia (AML) and myelodysplastic syndrome (MDS) with translocation
      t(1;3)(p36;q21). MEL1 (at chromosome band 1p36.3) is thought to be
      transcriptionally activated as a result of juxtaposition to the RPN1 gene at
      3q21. It is not known whether MEL1 expression is restricted to cases with this
      particular translocation. MATERIALS AND METHODS: Using real-time polymerase chain
      reaction, we measured MEL1 expression levels, normal bone marrow, and distinct
      blood cell fractions in 162 de novo AML patients. We also investigated the
      existence of an EVI1-like gene (EL1) by applying the same method. The existence
      of these transcripts was confirmed by Northern blot analysis. RESULTS: MEL1
      expression was detected in 87% (141/162) of de novo AML patients. The EL1
      transcript also was detected in the majority of the patients. EL1 expression
      levels highly correlated with MEL1 expression levels in AML cases. Variable
      MEL1/EL1 expression levels were observed. However, all the patients with
      favorable-risk karyotypes, i.e., with t(15;17), t(8;21), or inv(16), showed low
      MEL1/EL1 expression levels. Expression analysis of MEL1/EL1 compared with MDS1
      EVI1/EVI1 in distinct normal marrow or blood cell fractions revealed that 1) all
      four gene products are expressed in CD34(+) progenitor cell fractions; 2) both
      MEL1 and EVI1 are turned down in neutrophils and monocytes/macrophages; while 3)
      MDS1-EVI1 and EL1 remain expressed in mature blood cell fractions. CONCLUSION:
      Our data suggest that simultaneous low MEL1/EL1 expression in AML is abnormal and
      that favorable disease is highly associated with this abnormal phenotype.

PMID- 14585372
TI  - Comparative gene expression profile of chronic myeloid leukemia cells innately
      resistant to imatinib mesylate.
AB  - OBJECTIVE: Resistance to imatinib mesylate monotherapy is clearly a barrier to
      successful treatment of chronic myeloid leukemia (CML) patients. In some
      patients, resistance arises due to powerful selective pressure on rare cells that
      carry amplified copies of the BCR-ABL fusion oncogene or point mutations in the
      Bcr-Abl tyrosine kinase domain that affect binding of the drug to the
      oncoprotein. However, in a proportion of patients neither mechanism operates, and
      resistance appears to be a priori, existing prior to exposure to the drug. These
      mechanisms of imatinib resistance are poorly understood and may be heterogeneous.
      MATERIALS AND METHODS: We have previously described such innate resistance to
      imatinib in subclones of a myeloid leukemia cell line, KCL22, in which imatinib
      exposure inhibits the activity of Bcr-Abl and yet fails to induce apoptosis. We
      describe here whole-genome expression analysis of imatinib-sensitive and 
      resistant cells derived from the original KCL22 line, using Affymetrix microarray
      analysis. RESULTS: We detected differential expression of 39 genes that correlate
      with the imatinib-resistant phenotype. The resistant cells overexpress several
      genes associated with the suppression of apoptosis or with conferral of a
      transformed phenotype. CONCLUSION: Amongst the differentially-expressed genes
      correlating with imatinib resistance, several suggest the activation of
      alternative pathway(s) that maintain viability and growth independently of Bcr
      Abl kinase activity. Given the high rate of primary imatinib resistance in blast
      crisis, the potential of activating such alternative pathways appears to
      correlate with disease progression.

PMID- 14585373
TI  - Expression of osteoprotegerin mRNA and protein in murine megakaryocytes.
AB  - OBJECTIVE: Osteoprotegerin (OPG) is a soluble member of the tumor necrosis factor
      receptor superfamily critically involved in the regulation of bone resorption.
      Within the bone microenvironment, OPG is abundantly produced by
      osteoblast/stromal cells, and its expression is regulated by transforming growth
      factor-beta(1) (TGF-beta(1)). However, OPG expression and regulation in primary
      hematopoietic cells have not been fully investigated. MATERIALS AND METHODS: Opg
      mRNA was studied in murine hematopoietic cells by semiquantitative reverse
      transcriptase-polymerase chain reaction. The OPG protein was identified by
      immunofluorescence labeling and secretion was assessed by enzyme-linked
      immunosorbent assay. RESULTS: Opg transcripts were detected in platelets,
      megakaryocytes (MK), monocytes, and B lymphocytes, but not in erythroblasts,
      neutrophils, and T lymphocytes. Mature MK and proplatelets exhibited strong
      immunostaining for OPG outside the storage alpha-granules, and secretion was
      detected in the conditioned medium. To analyze whether opg transcription in MK
      was influenced by TGF-beta(1), the opg/GpIIb mRNA ratio was compared in cultured
      MK derived from TGF-beta(1) null mutants and wild-type littermates without or
      after the addition of bioactive TGF-beta(1). No difference was seen, indicating
      that opg expression in MK was not modulated by TGF-beta(1). However, mRNA levels
      were increased when thrombopoietin was present in the culture medium, suggesting
      that MK maturation was correlated with enhanced opg expression. CONCLUSIONS: With
      these results we document for the first time that murine MK and platelets express
      OPG. This suggests a novel role for MK in bone homeostasis, in addition to its
      role in vascular homeostasis.

PMID- 14585374
TI  - p38 MAP kinase activation mediates gamma-globin gene induction in erythroid
      progenitors.
AB  - OBJECTIVE: Our goal was to determine the role of p38 mitogen-activated protein
      kinase (MAPK) signaling in fetal hemoglobin (HbF) induction. Two histone
      deacetylase inhibitors (HDAIs), sodium butyrate (NB), and trichostatin (TSA) and
      hemin were analyzed. In addition, the effect of direct activation of p38 MAPK on
      gamma-globin gene activity was studied. METHOD: Primary erythroid progenitors
      derived from peripheral blood mononuclear cell and K562 erythroleukemia cells
      were analyzed. Cells were grown in NB, TSA, hemin, or anisomycin either alone or
      in the presence of the p38 MAPK inhibitor SB203580. The effects of the various
      treatments on gamma-globin RNA, HbF, and phosphorylated p38 MAPK levels were
      measured by RNase protection assay, alkaline denaturation, and Western blot
      analysis, respectively. A K562 stable line overexpressing constitutively active
      p38 MAPK was established using MAPK kinase kinase 3 (MKK3) and MKK6, the
      immediate upstream activators of p38. The direct effect of p38 MAPK
      overexpression on gamma-globin mRNA synthesis was analyzed. RESULTS: NB and TSA
      activated p38 MAPK and increased gamma-globin mRNA levels in K562 cells and
      primary erythroid progenitors. Pretreatment with SB203580 blocked p38 MAPK and
      gamma-globin gene activation. In contrast, no change in p38 activity was observed
      with hemin inductions. Direct activation of p38 by anisomycin or constitutive
      overexpression also increased gamma-globin mRNA in the absence of HbF inducers in
      wild-type K562 cells and in the MKK stable lines. CONCLUSION: This study supports
      a novel role for p38 MAPK in gamma-globin regulation in human erythroid
      progenitors.

PMID- 14585375
TI  - Hematopoietic senescence is postponed and hematopoietic stem cell function is
      enhanced by dietary restriction.
AB  - OBJECTIVE: The aim of this study was to test dietary restriction (DR) as an
      intervention to alleviate senescence-associated functional defects in
      hematopoietic stem cells (HSCs). MATERIALS AND METHODS: BALB/cByJ (BALB) mice
      were fed ad libitum (AL) or were diet restricted (DR) to 75% of the AL food
      intake after 1 month of age. Peripheral blood and bone marrow cell compositions
      were compared in 3- and 25-month-old AL (AL-3, AL-25) mice and in 25-month-old DR
      (DR-25) mice using fluorescence-activated cell staining. Relative HSC functions
      in vivo were compared using competitive repopulation, and were also tested in 6
      month-old BALB mice to measure the effects of short-term DR. RESULTS: Compared to
      AL-3, AL-25 blood had significantly lower levels of red blood cells and
      hemoglobin. AL-25 marrow contained less than half the concentration of Lin(
      )CD34(-)Sca1(+)CD117(+) HSCs and showed only half the in vivo functional ability
      of AL-3 marrow. In vivo, AL-25 HSCs failed to produce the strong correlations
      over time that demonstrate clonal stability during competitive repopulation.
      These correlations were shown in AL-3 HSCs. DR for 24 months alleviated
      hematopoietic deficiencies in the blood, increased concentrations of bone marrow
      Lin(-)CD34(-)Sca1(+)CD117(+) HSCs and improved HSC functional abilities in DR-25
      mice to values far greater than those in normally aged mice. Surprisingly, HSC
      function in 25-month-old DR mice was better than that in young adults. Degrees of
      recipient repopulation by HSCs from DR-25 mice also correlated well over time,
      demonstrating clonal stability. Short-term DR for 5 months also improved HSC
      function, but to a much smaller degree. CONCLUSIONS: Aged BALB mice show
      hematopoietic and HSC senescence and clonal succession. Lifelong DR slows
      hematopoietic senescence and prevents HSC aging.

PMID- 14585377
TI  - Donor cell expansion is delayed following nonablative in utero transplantation to
      treat murine mucopolysaccharidosis type VII.
AB  - To block development of progressive childhood diseases, in utero transplantation
      (IUTx) requires immediate and significant donor peripheral blood (PB) cell
      amplification. To date, negligible and nontherapeutic donor PB cell levels have
      been observed postnatally, except in patients with immunodeficiency diseases.
      Donor cell fate in utero still is not clear. Ease of identifying and quantifying
      beta-glucuronidase (GUSB)-expressing donor cells in GUSB-null
      mucopolysaccharidosis type VII (MPSVII) mouse recipients allowed us to evaluate
      temporal donor cell engraftment and amplification post-IUTx. Like humans, MPSVII
      mice are unable to catabolize lysosomal glycosaminoglycans and progressively
      develop severe storage disease unless they are treated early in life.IUTx
      recipients were nonablated MPSVII fetuses and genetically stem cell-deficient,
      and hence myeloablated, W(41)/W(41) MPSVII fetuses. Donor GUSB+ cells were
      identified and counted in histochemical tissue sections. Quantitative results
      were confirmed by flow cytometry, enzyme analysis, and histopathology. Whereas
      GUSB+ cells engraft in most tissues in utero, significant amplification does not
      occur until the first postnatal week in the nonablated MPSVII hosts. In contrast,
      genetically myeloablated MPSVII recipients display widely distributed donor cell
      replacement accompanied by extensive amplification in utero. In both models,
      storage is alleviated in adult tissues with significant donor cell repopulation.
      To become therapeutic, IUTx must overcome the limitations of donor cell expansion
      in the highly competitive fetal environment. Fortunately, nonablative mechanisms
      to amplify cells in utero are coming on line.

PMID- 14585376
TI  - In vitro toxicity of three new antitumoral drugs (trabectedin, aplidin, and
      kahalalide F) on hematopoietic progenitors and stem cells.
AB  - OBJECTIVE: In addition to neutropenias and/or thrombocytopenias as a short-term
      effect, antineoplastics also can produce long-term effects as a consequence of
      damage to the hematopoietic stem cells. The aim of the present study was to
      evaluate the toxicity of three marine-derived antineoplastics on murine
      hematopoietic stem cells. These antitumoral compounds currently are being
      evaluated in patients in phase II (aplidin and kahalalide F) and phase II/III
      (trabectedin) clinical trials. MATERIALS AND METHODS: Long-term competitive
      repopulating assays were performed in mice to analyze toxic effects on the
      hematopoietic stem cells responsible for the multipotential long-term
      repopulation of hematopoiesis. Furthermore, granulocytic and T- and B-lymphoid
      lineages were studied, as well as myeloid (CFU-GM) and megakaryocytic (CFU-Meg)
      progenitors. RESULTS: When cells were treated in vitro for 24 hours with CFU-GM
      IC(50) dose of trabectedin (9.59+/-4.96 nM), no significant effects were observed
      in the stem cells. The dose of trabectedin that produced 90% of inhibition in CFU
      GM (IC(90): 23.71+/-1.27 nM) only inhibited 45% survival of stem cells. Doses of
      aplidin that produced reductions of 50% (56.9+/-13.32 nM) or 90% (195.88+/-21.39
      nM) in myeloid progenitors did not show any effect on hematopoietic stem cells.
      Kahalalide F did not show any toxic effect in either short-term or long-term
      repopulating cells up to 10 microM. CONCLUSIONS: Our data show that the
      hematopoietic stem cells effects of antitumoral drugs can be properly
      characterized by the murine competitive repopulating assays. Our results suggest
      that long-term myelosuppression as a consequence of trabectedin, aplidin, or
      kahalalide F treatment would not be expected.

PMID- 14585378
TI  - Activation of the G-CSF and Flt-3 receptors protects hematopoietic stem cells
      from lethal irradiation.
AB  - OBJECTIVE: Synergy between Flt-3 ligand and G-CSF produces a marked expansion of
      hematopoietic progenitor cells and mobilizes large numbers of stem cells into the
      peripheral blood. To determine if the activation of the Flt-3 and G-CSF receptors
      enhances the regenerative capacity of the hematopoietic compartment, we evaluated
      whether activation of these receptors augments stem cell recovery following
      lethal doses of radiation. METHODS: C57BL/6 mice received a single injection of
      the bi-functional Flt-3 and G-GSF agonist progenipoietin-1, 24 hours prior to
      exposure to 1100 cGy of gamma radiation. Survival, hematopoietic reconstitution,
      and competitive repopulation potential were evaluated. RESULTS: All cytokine
      treated mice survived for up to 9 months. Radioprotected recipients exhibited
      stable multilineage hematopoiesis and recovered normal numbers of T cells, B
      cells, and myelomonocytic cells in the blood, bone marrow, and thymus. Between 2
      and 3 weeks following radiation, cytokine-treated mice demonstrated threefold
      higher serum hemoglobin levels, 10-fold higher nucleated blood cell counts, and
      20-fold higher platelet counts compared to controls. Radioprotection of self
      renewing hematopoietic stem cells was revealed by multilineage hematopoietic
      reconstitution following transplantation in a competitive repopulation assay. To
      further evaluate the extent of cytokine-induced radioprotective activity, a
      cohort of mice received a second cycle of cytokine treatment and a second
      exposure to radiation (1100 cGy). Survival of this serially irradiated group was
      70% and analysis of the peripheral blood revealed sustained multilineage
      hematopoiesis. CONCLUSION: These results demonstrate that activation of both the
      Flt-3 and G-CSF receptors provides a high degree of radioprotection to the
      hematopoietic progenitor cell and stem cell compartment.

PMID- 14585379
TI  - CD26 is essential for normal G-CSF-induced progenitor cell mobilization as
      determined by CD26-/- mice.
AB  - OBJECTIVE: In spite of the wide usage of mobilized peripheral blood hematopoietic
      stem and progenitor cells (HSC/HPC) for transplantation, the mechanism of
      granulocyte colony-stimulating factor (G-CSF)-induced HSC/HPC mobilization has
      yet to be fully determined. Our previous studies suggested that that G-CSF
      induced mobilization may involve the extracellular peptidase CD26
      (DPPIV/dipeptidylpeptidase IV). We set out to establish whether CD26 was an
      essential component of normal G-CSF-induced mobilization of HSC/HPC. MATERIALS
      AND METHODS: Normal wild-type (WT) control C57BL/6 mice and CD26 knockout (CD26(
      /-)) mice, also on a C57BL/6 background, were treated with or without G-CSF and
      peripheral blood cells, bone marrow cells, and spleen cells were assessed for CFU
      GM, BFU-E, and CFU-GEMM content. RESULTS: No statistical difference in the number
      of CFU-GM, BFU-E, or CFU-GEMM in the peripheral blood, bone marrow, or spleen of
      untreated WT vs untreated CD26(-/-) mice was observed. G-CSF treatment of WT mice
      resulted in the mobilization of HPC into the peripheral blood. The number of HPC
      detected in G-CSF-treated CD26(-/-) mouse peripheral blood was significantly less
      than the corresponding number of HPC detected in G-CSF-treated WT mouse
      peripheral blood after either a 2- or 4-day G-CSF regimen. CONCLUSIONS: CD26
      plays a critical role in G-CSF-induced mobilization of HPC.

PMID- 14585380
TI  - A review of lung transplant donor acceptability criteria.

PMID- 14585381
TI  - Heart transplantation in children after mechanical circulatory support with
      pulsatile pneumatic assist device.
AB  - BACKGROUND: Mechanical support with a pulsatile pneumatic ventricular assist
      device (VAD) is a complex rescue procedure performed in children with untreatable
      cardiogenic shock. Its impact on early and long-term survival after subsequent
      heart transplantation (HTx) remains to be determined. METHODS: We reviewed
      retrospectively the course of 95 children (median age, 8 years; range, 8 days-17
      years; body weight, 24 kg; range, 3-110 kg) who underwent HTx. Group A, the
      elective-HTx group, consists of 33 children who were treated as outpatients
      before transplantation. Group B, the emergency-HTx group, has 44 children who
      were critically ill and hospitalized before transplantation but without
      ventricular assist devices, whereas Group C, the VAD-HTx group, consists of 18
      children resuscitated and supported with pulsatile pneumatic VADs for a median
      time of 20 days. RESULTS: Overall actuarial survival after cardiac
      transplantation was 86% at 1 month, 82% at 1 year, and 78% at 5 years, without
      significant differences among the 3 sub-groups. Group A had the best long-term
      survival rate, 88% at 1 month, 88% at 1 year, and 80% at 5 years. Group B had a
      survival rate of 88% at 1 month, 82% at 1 year, and 79% at 5 years. Group C had a
      survival rate of 72% at 1 month, 72% at 1 year, and 72% at 5 years. We found no
      differences in neurologic outcome, acute cardiac rejection, or transplant
      failure. The survival rate was significantly better in the children with
      cardiomyopathy compared with those with congenital heart defects (p = 0.014).
      CONCLUSIONS: Bridging to HTx with a pulsatile pneumatic VAD is a safe procedure
      in pediatric patients. After HTx, overall survival of these children is similar
      to that of patients who were bridged with inotropes or who were awaiting heart
      transplantation electively.

PMID- 14585382
TI  - Differential regulation of Ca2+-dependent ATPase-activity in left ventricular
      myocardium during mechanical circulatory support.
AB  - BACKGROUND: Myocardial recovery is observed in some end-stage heart failure
      patients after mechanical circulatory support. The sarcoplasmic reticulum Ca(2+)
      adenosine triphosphatase (Ca2+-ATPase) activity is down-regulated in failing
      myocardium and contributes to heart failure-associated contraction/relaxation
      abnormalities. Regulation of Ca(2+)-ATPase after mechanical support was shown to
      be heterogeneous. Thus, we analyzed Ca(2+)-ATPase activity and protein expression
      in the paired myocardial samples of 21 patients supported by ventricular assist
      devices to identify factors that influence restoration of the Ca(2+)-transient
      after ventricular assist device support. METHODS: We measured Ca(2+)-ATPase
      activity using a reduced nicotinamide-adenine dinucleotide-coupled reaction,
      determined sarcoplasmic reticulum Ca(2+)-dependent ATPase protein using Western
      blotting, and determined 4-hydroxyproline using amino-acid analysis. RESULTS: The
      mean Ca(2+)-ATPase activity decreased at assist-device implantation and slightly
      increased at transplantation, but remained significantly lower than in non
      failing donor hearts. However, individual responses were heterogeneous. Patients
      with older age, increased left ventricular diameter, and increased 4
      hydroxyproline content showed down-regulation of Ca(2+)-ATPase activity, whereas
      we found up-regulation in patients with low values for these parameters after
      assist-device support. CONCLUSIONS: Sarcoplasmic reticulum Ca(2+)-ATPase
      activity, which influences the myocardial Ca(2+)-transient, generally is not
      restored to normal values in assist-device-supported hearts, but depends on a
      combined score of the left ventricular end-diastolic diameter, degree of
      ventricular fibrosis, and age of the patient at the time of assist-device
      implantation.

PMID- 14585383
TI  - Acute and chronic pleural complications in lung transplantation.
AB  - BACKGROUND: Lung transplant recipients may have pleural complications. However,
      the influence of these complications on the prognosis is not well known. METHODS:
      We analyzed pleural complications and clinical and radiologic data from 100
      patients who underwent lung transplantation in a general hospital in a 9-year
      period. Pre-operative evaluation, surgical protocol, immunosuppressive regimen,
      and follow-up were carried out systematically. Chest computerized tomography (CT)
      was performed at 3 and 12 months after transplantation. RESULTS: All patients had
      early post-operative pleural effusion ipsilateral to the graft, which required
      drainage for a mean of 19.3 days (range, 5-52 days). Thirty-four patients had 43
      acute pleural complications: 15 hemothoraxes, 10 persistent air leaks, 8
      pneumothoraxes, 7 transient air leaks, and 3 empyemas. Multivariate analysis
      showed hemothorax and persistent air leak were associated with increased post
      operative mortality (p = 0.024, p = 0.011, respectively). Post-operative
      mortality was not associated with any pre-transplant variable. Chest CT findings
      at 3 months revealed > or =1 pleural alteration in 58 of 70 patients (83%): 34
      post-operative residual ipsilateral pleural effusions; 36 pleural thickenings;
      and 3 residual pneumothoraxes, 1 with a coexisting bronchial dehiscence. Chest CT
      at 12 months showed pleural alterations in 50 of 58 patients (86%): pleural
      thickening in 48, calcification in 4, and residual pleural effusion in 4.
      CONCLUSIONS: Pleural complications are common in lung transplant recipients.
      Hemothorax and persistent air leak are associated with increased post-operative
      mortality. Chest CT showed pleural alterations in most patients 12 months after
      transplantation.

PMID- 14585384
TI  - Should we ventilate or cool the pulmonary graft inside the non-heart-beating
      donor?
AB  - BACKGROUND: The ideal preservation method during the warm ischemic period in the
      non-heart-beating donor (NHBD) remains unclear. In this study we compare the
      protective effect of ventilation vs cooling of the non-perfused pulmonary graft.
      METHODS: Domestic pigs (30.8 +/- 0.35 kg) were divided into 3 groups. In Group I,
      lungs were flushed with cold Perfadex solution, explanted and stored in saline (4
      degrees C) for 4 hours (HBD, n = 5). Pigs in the 2 study groups were killed by
      myocardial fibrillation and left untouched for 1 hour. Lungs in Group II were
      ventilated (NHBD-V, n = 5) for 3 hours. Lungs in Group III were topically cooled
      (NHBD-TC, n = 5) in situ for 3 hours with saline (6 degrees C) infused via intra
      pleural drains. Thereafter, the left lungs from all groups were prepared for
      evaluation. In an isolated circuit the left lungs were ventilated and reperfused
      via the pulmonary artery (PA) with autologous, hemodiluted, deoxygenated blood.
      Hemodynamic, aerodynamic and oxygenation parameters were measured at 37.5 degrees
      C and a PA pressure of 20 mm Hg. The wet:dry weight ratio (W/D) was calculated
      after reperfusion. RESULTS: Pulmonary vascular resistance, oxygenation index and
      W/D weight ratio were significantly worse in NHBD-V (3,774 +/- 629 dyn sec cm(
      5), 3.43 +/- 0.5, 6.98 +/- 0.42, respectively) compared with NHBD-TC (1,334 +/-
      140 dyn sec cm(-5), 2.47 +/- 0.14, 5.72 +/- 0.24, respectively; p < 0.01, p <
      0.05 and p < 0.05, respectively) and HBD (1,130 +/- 91 dyn sec cm(-5), 2.25 +/-
      0.09, 5.23 +/- 0.49, respectively; p < 0.01, p < 0.01 and p < 0.05, respectively
      groups). No significant differences were observed, however, in any of these
      parameters between NHBD-TC and HBD (p = 0.46, p = 0.35 and p = 0.12,
      respectively). CONCLUSION: These results indicate that cooling of the pulmonary
      graft inside the cadaver is the preferred method in an NHBD protocol. It is also
      confirmed that 1 hour of warm ischemia does not diminish graft function upon
      reperfusion.

PMID- 14585385
TI  - Pharmacologic pre-conditioning and controlled reperfusion prevent ischemia
      reperfusion injury after 30 minutes of hypoxia/ischemia in porcine hearts.
AB  - BACKGROUND: Hearts from non-heart-beating organ donors are not transplanted
      because of risk of ischemia-reperfusion injury. We tested whether pharmacologic
      pre-conditioning with adenosine and the Na(+)/H(+) exchanger inhibitor,
      cariporide, combined with controlled reperfusion, would prevent injury in porcine
      hearts that had sustained 30 minutes of hypoxia/ischemia in closed-chest animals.
      METHODS: Hearts from Yorkshire pigs (100 kg) were studied in 3 groups. Group 1
      (control) hearts were surgically removed while beating. Group 2 hearts were
      harvested from animals made hypoxic by discontinuing mechanical ventilation for
      30 minutes. Group 3 hearts were hypoxic as in Group 2, but these animals received
      adenosine (40 mg) and cariporide (400 mg) 10 minutes before stopping ventilation.
      Cardiac function in all groups was assessed ex vivo in a working heart apparatus
      in which pressure and flow measurements were made over 3 hours. Controlled
      reperfusion in Group 3 hearts used leukocyte-depleted blood perfusate containing
      free radical scavengers. Myocardial injury was assessed on the basis of perfusate
      creatine phosphokinase activity and histopathologically determined injury score.
      RESULTS: Groups 1 and 3 hearts could be resuscitated to perform work equivalently
      during the entire reperfusion period and showed positive responses to increases
      in pre-load and norepinephrine. Group 2 hearts could not perform work. After 3
      hours, Group 2 hearts showed significantly higher creatine phosphokinase and
      histopathologic injury scores compared to with Groups 1 and 3, which were not
      significantly different from each other. CONCLUSIONS: Pharmacologic pre
      conditioning and controlled reperfusion effectively protect non-beating porcine
      hearts from injury after 30 minutes of hypoxia/ischemia in situ.

PMID- 14585386
TI  - Enhanced cardioprotection of the rat heart during hypothermic storage with
      combined Na+ - H+ exchange inhibition and ATP-dependent potassium channel
      activation.
AB  - BACKGROUND: We investigated the ability of mitochondrial adenosine triphosphate
      dependent potassium-channel activation to augment the protection of Na(+)-H(+)
      exchanger inhibition in isolated working rat hearts after 6 hours of hypothermic
      storage in an extracellular-based cardioplegic solution. METHODS: We treated
      hearts with the potassium-channel openers diazoxide (100 micromol/liter) or BMS
      180448 (10 micromol/liter) or with the Na(+)-H(+) exchanger inhibitor cariporide
      (10 micromol/liter). Cariporide also was administered in combination with either
      diazoxide or BMS-180448 in 2 other treatment groups. All hearts were arrested and
      stored at 2 to 3 degrees C. After storage, we reperfused hearts for 10 minutes
      before performing work for a further 15 minutes, and then we measured and
      assessed cardiac function using a 2-way analysis of variance model. RESULTS:
      Neither diazoxide nor BMS-180448 significantly improved recovery of cardiac
      output. Cariporide therapy significantly improved cardiac output compared with
      control. However, we obtained the greatest recovery of cardiac output when we
      combined cariporide with either diazoxide or BMS-180448. CONCLUSIONS: Cariporide
      is more cardioprotective than the potassium-channel openers diazoxide and BMS
      180448 after prolonged hypothermic storage. Co-administration of diazoxide or BMS
      180448 with cariporide results in additive cardioprotection, with significantly
      improved cardiac function when compared with either treatment given alone. Such a
      combination could be used to improve the functional recovery of hearts stored for
      cardiac transplantation.

PMID- 14585387
TI  - Change in quality of life from after left ventricular assist device implantation
      to after heart transplantation.
AB  - BACKGROUND: No studies have analyzed quality of life (QOL) from before to after
      heart transplantation in patients with a left ventricular assist device (LVAD).
      Therefore, the purpose of this longitudinal, multi-site study was to compare QOL
      outcomes of patients listed for heart transplantation who required a left
      ventricular assist device (LVAD) at 3 months after implantation of an LVAD vs 3
      months after heart transplantation. METHODS: A non-random sample of 40 patients
      (predominantly middle-aged, married, white men), who had paired data at both 3
      months after LVAD implantation and 3 months after heart transplantation, were
      investigated. Patients completed self-report questionnaires (with acceptable
      reliability and validity) at both time periods, including the Quality of Life
      Index, Rating Question Form, Heart Failure Symptom Checklist, Sickness Impact
      Profile, LVAD Stressor Scale (completed only after LVAD implant), Heart
      Transplant Stressor Scale (completed only after heart transplant) and Jalowiec
      Coping Scale. Descriptive analyses and comparative analyses using paired t-tests
      were performed with statistical significance set at 0.01. RESULTS: Patients were
      significantly more satisfied with their lives overall and with their health and
      functioning at 3 months after heart transplantation as compared with 3 months
      after LVAD implantation. Mobility, self-care ability, physical ability and
      overall functional ability improved from 3 months after LVAD implant to 3 months
      after heart transplant. There was significantly less symptom distress after LVAD
      implant as compared with after heart transplant for the neurologic, dermatologic
      and physical sub-scales. Work/school/financial stress was significantly lower
      after heart transplant vs after LVAD implant. In contrast, 2 other areas of
      stress were significantly lower after LVAD implant vs after heart transplant:
      self-care stress and hospital/clinic-related stress. CONCLUSIONS: Differences
      were found in QOL outcomes at 3 months after LVAD implant as compared with 3
      months after heart transplant. Our findings point out specific areas of concern
      with respect to QOL after LVAD implant and post-transplant, some of which are
      amenable to health-care provider interventions.

PMID- 14585388
TI  - Psychosocial vulnerability, physical symptoms and physical impairment after lung
      and heart-lung transplantation.
AB  - BACKGROUND: Many lung and heart-lung transplant recipients experience distressing
      physical symptoms and elevated physical impairment levels. Although post
      transplant complications and secondary illnesses may largely account for these
      health limitations, patients' psychosocial well-being may influence them as well.
      We examined the contribution of psychosocial variables to patients' experience of
      physical symptoms and physical impairment. METHODS: The study consisted of a
      cross-sectional sample of 50 patients (36 lung, 14 heart-lung) at between 2 and
      17 months post-transplant. They were interviewed to assess physical symptoms,
      current physical impairment and psychosocial well-being in the areas of mental
      health, sense of mastery and coping. Medical record reviews established the
      presence of medical complications and secondary illnesses concurrent with the
      interviews. Descriptive analyses examined the range of symptoms and levels of
      physical impairment experienced. Bivariate analyses and multivariate linear
      regression examined relationships between key variables. RESULTS: Average number
      of physical symptoms and level of physical impairment met or exceeded levels
      reported in other transplant samples. Elevated depressive and anxiety symptoms, a
      low sense of mastery, and the presence of concurrent medical complications were
      each associated with increased number of physical symptoms and physical
      impairment level. When the impact of concurrent medical complications was
      controlled, recipients with elevated psychologic distress remained significantly
      more likely to report more physical symptoms and higher physical impairment
      levels. CONCLUSIONS: Patients' physical health status may be influenced by many
      factors. To the extent that psychologic distress increases the likelihood of
      perceived physical limitations, timely identification and treatment of distress
      may help to maximize quality of life after lung and heart-lung transplantation.

PMID- 14585389
TI  - Angiographic regression of cardiac allograft vasculopathy after introducing
      sirolimus immunosuppression.
AB  - We describe a 33-year-old heart transplant recipient who experienced several
      episodes of early Grade IIIA rejection and aggressive allograft vasculopathy,
      seen with serial coronary angiography. Two years after transplantation, we added
      sirolimus therapy to the patient's immunosuppressive regimen, and a further
      coronary angiogram 1 year later showed regression of the graft vasculopathy.

PMID- 14585390
TI  - Interleukin-17 stimulates release of interleukin-8 by human airway smooth muscle
      cells in vitro: a potential role for interleukin-17 and airway smooth muscle
      cells in bronchiolitis obliterans syndrome.
AB  - Bronchiolitis obliterans syndrome is the major constraint on the long-term
      survival after lung transplantation. Both neutrophils and interleukin (IL)-8, a
      potent neutrophil attractant, have been shown to play an important role in the
      pathophysiology of obliterative bronchiolitis. We investigated the potential role
      of human airway smooth muscle cells in obliterative bronchiolitis by studying
      their release of IL-8 after stimulation with IL-17, a novel T-cell-derived
      chemokine capable of attracting and activating neutrophils. We demonstrated a
      significant increase in IL-8 release, reaching a concentration of 86.6 ng/ml (SEM
      1.9 ng/ml) with 100 ng/ml IL-17 (p < 0.01, n = 4), as compared with non
      stimulated cells. This IL-17-mediated IL-8 release could not be inhibited by
      dexamethasone. We conclude that human airway smooth muscle cells may play an
      important pro-inflammatory role in neutrophilic inflammatory diseases such as
      chronic rejection after lung transplantation; furthermore, IL-17 may be the link
      between lymphocytes and neutrophils.

PMID- 14585391
TI  - Value of circulating adhesion molecules in assessing cardiac allograft
      vasculopathy.
AB  - Circulating adhesion molecules have been implicated in the development of
      spontaneous and transplant coronary artery disease. We analyzed soluble (s)
      intercellular adhesion molecule 1 (sICAM-1), vascular cell adhesion molecule 1
      (sVCAM-1), and sE-selectin levels from the coronary sinuses of 25 cardiac
      allograft recipients, and we correlated these molecules with the degree of acute
      rejection detected in endomyocardial biopsy specimens and the presence of
      transplant vasculopathy assessed with coronary angiography. We found that sVCAM-1
      significantly increased in patients with transplant vasculopathy compared with
      those without transplant vasculopathy, whereas sE-selectin and sICAM-1 did not.
      Therefore, increased coronary sinus levels of sVCAM-1 is a reliable marker in
      assessing cardiac transplant vasculopathy.

PMID- 14585392
TI  - Present state of hepatitis E virus epidemiology in Tokyo, Japan.
AB  - Recently studies have reported the possibility that an indigenous hepatitis E
      virus (HEV) exists in Japan, but the epidemiological features of HEV in Japan are
      inadequate to make a judgment. In order to search the present state of HEV
      infection in Japan, we used ELISA to test 1033 sera from residents living in
      Tokyo and the Tokyo suburbs, for the presence of the antibody against HEV. The
      positive rate of anti-HEV IgG was 15.4% in all liver disease patients (68 of
      440), 3% (6/200) in healthy individuals and 0.4% in infants (1/246), respectively
      (P<0.01). Anti-HEV IgG was seen in 17.6% (35/199) of liver disease patients of
      unknown etiology; 29.4% (5/17) of fulminant hepatitis, 17% of acute hepatitis
      (15/88) and 16% of chronic hepatitis (15/94). Anti-HEV IgG co-existed with
      hepatitis B virus and hepatitis C virus in 23.6% (21/89) and 7.9% (12/152),
      respectively. Furthermore, the prevalence of anti-HEV IgG was significantly
      higher in hemodialysis patients (18/60: 30%) and hospital workers (8/87: 9.2%)
      than in the healthy population (P<0.01). Anti-HEV IgM was detected in 0.1% of all
      samples tested (1/1033). The prevalence of anti-HEV IgG increased with age. No
      individuals with HEV antibody had a recent history of visiting countries where
      hepatitis E is endemic. These results indicate that generally 15.4% of Japanese
      patients with liver diseases had a history of HEV infection in the past. The
      routes of transmission of HEV require clarification in Japan.

PMID- 14585393
TI  - Epidemiology of SEN virus infection among patients with hepatitis B and C in
      China.
AB  - China is highly endemic for viral hepatitis. In the present study, we
      investigated the clinical significance and molecular analysis of SEN virus (SEN
      V) infection in patients with chronic hepatitis B and C in YanBian city, China.
      Serum samples were obtained from 71 patients with hepatitis B and C who visited
      YanBian hospital in the north-east of China. Detection of SEN-V DNA was performed
      by nested polymerase chain reaction (PCR) using primer pairs in the 5'
      untranslated region. SEN-V DNA was present in 14/23 (63.9%), 12/15 (80.0%), 5/7
      (71.4%), 13/18 (72.2%), 7/8 (87.5%), 1/1 (100%) of the patients with type B (B)
      chronic hepatitis (CH), B-liver cirrhosis (LC), B-hepatocellular carcinoma (HCC),
      type C (C)-CH, C-LC, C-HCC, respectively. The highest prevalence of SEN-V DNA was
      seen in the various age groups over 40 years old. There was no significant
      correlation of clinical parameters between SEN-V DNA-positive and -negative
      patients with type B and C liver diseases. The YanBian isolates showed 71.4-95.0%
      homology to isolates reported previously. In conclusion, the prevalence of SEN-V
      infection in YanBian City was high but SEN-V coinfection did not seem to modify
      the serological features of chronic hepatitis B and C in China.

PMID- 14585394
TI  - Pretreatment hepatitis C virus dynamics for predicting virological response to
      interferon-alpha2b monotherapy in patients with chronic hepatitis C virus
      infection.
AB  - One hundred and forty-one patients with chronic hepatitis C virus (HCV) infection
      treated with 6 MIU of interferon (IFN)-alpha2b for 24 weeks were studied to
      compare pretreatment viral dynamics during 1 month before the initiation of
      treatment (DeltaHCV) with other predictive factors. The patients were classified
      into three groups according to DeltaHCV: the Increase group (DeltaHCV >0.20log
      copies/ml/month), the Stable group (-0.20</=DeltaHCV</=0.20log copies/ml/month)
      and the Decrease group (DeltaHCV<-0.20log copies/ml/month). The sustained
      response (SR) rates were 0/40 (0%) in the Increase group, 6/54 (11.1%) in the
      Stable group and 25/47 (53.2%) in the Decrease group (P<0.0001). Based on the HCV
      RNA level at baseline, the SR rates were lower in the Increase group than that in
      the Decrease group in less than 5.0log copies/ml (0% vs. 100.0%, P=0.0132) and at
      5.00-5.49log copies/ml (0% vs. 81.8%, P=0.0270), respectively. The pretreatment
      HCV RNA decrease was determined as independent predictors of SR by multivariable
      logistic regression analysis (P<0.0001). For serial assays of HCV RNA during
      treatment, there was not significant difference in mean HCV RNA level at baseline
      but was significantly different on day 14 between the Decrease and the
      Nondecrease groups (1.15 vs. 2.21log copies/ml, P=0.0417). These results suggest
      that DeltaHCV is independently associated with the IFN response and is useful for
      determining the indication of IFN treatment.

PMID- 14585395
TI  - Assessment of 287 Japanese cases of drug induced liver injury by the diagnostic
      scale of the International Consensus Meeting.
AB  - Two hundred and eighty seven Japanese cases of drug induced liver injury were
      assessed by the diagnostic scale of the International Consensus Meeting (ICM).
      They were classified to the hepatocellular (55%), mixed (24%) and cholestatic
      (22%) type according to the type of liver injury. Five cases were diagnosed as
      'unrelated', since the reaction occurred more than 15 days after stopping the
      drug. The remaining 282 cases were classified to 69 cases of 'highly probable',
      170 cases of 'probable', 39 cases of 'possible', and four cases of 'unlikely'.
      The cases with positive drug-lymphocyte stimulation test (DLST) and with
      eosinophilia distributed to higher scores. Although the diagnostic scale of the
      ICM was found to be also useful for Japanese cases, the modification of the scale
      including the data of DLST and eosinophilia together with some other
      modifications were recommended in the view of the present status of Japan. Using
      the modified diagnostic scale, the 287 cases were classified to 173 cases of
      'highly probable', 102 cases of "probable', 11 cases of 'possible', and one case
      of 'unlikely'. Although the modified diagnostic scale seems better than the
      original one, further assessment of the modified scale using many Japanese cases
      is needed for the further improvement of the scale.

PMID- 14585396
TI  - Assessment of Kupffer cells by ferumoxides-enhanced MR imaging is beneficial for
      diagnosis of hepatocellular carcinoma: comparison of pathological diagnosis and
      perfusion patterns assessed by CT hepatic arteriography and CT
      arterioportography.
AB  - To investigate the clinical significance of the radiographic assessment of
      Kupffer cells and hemodynamics in the diagnosis of hepatocellular nodules, both
      magnetic resonance (MR) imaging enhanced by ferumoxides and CT hepatic
      arteriography (CTHA)/CT arterioportography (CTAP) were undertaken for 118
      patients with 158 primary nodular hepatocellular lesions. The radiographic
      findings were analyzed in the context of the pathological diagnosis. Among
      nodules presumed to be pre- or early HCC by CTHA/CTAP, all 13 hyperintense
      nodules identified by MR imaging (MRI) were found pathologically to be
      hepatocellular carcinoma (HCC). In contrast, in 14 hypointense nodules, no
      advanced (moderately or poorly differentiated) HCC was pathologically identified
      and none of these progressed to advanced HCC during the follow up period (mean:
      24 months). Instead, 78% of these cases were pathologically confirmed as
      dysplastic nodules. For the 16 lesions undetectable by CTHA/CTAP, four of eight
      (50%) hypointense nodules turned out to be dysplastic nodules and one
      hyperintense lesion was HCC. Signal intensity by ferumoxides-enhanced MRI showed
      a strong correlation with the increase or decrease of Kupffer cells assessed by
      immunohistochemistry. Assessment of Kupffer cells by ferumoxides-enhanced MRI is
      beneficial for the accurate diagnosis of primary hepatocellular nodules that are
      considered borderline or early stage HCC by their hemodynamic profile.

PMID- 14585397
TI  - Expressions of transforming growth factor (TGF)-beta1 and TGF-beta type II
      receptor and their relationship with apoptosis during chemical
      hepatocarcinogenesis in rats.
AB  - The expression of transforming growth factor (TGF)-beta1, which regulates cell
      proliferation, is tightly associated with that of TGF-beta type II receptor
      (TGR2), and has been regarded as an important change during hepatocarcinogenesis.
      Our aim in this study was to investigate the expression and localization of TGF
      beta1 and TGR2 and to determine their relationships with apoptosis in chemical
      hepatocarcinogenesis of the rat produced by Solt and Farber's method. Northern
      blot analysis showed that a slight increase of TGF-beta1 transcripts and a
      decrease of TGR2 transcripts during hepatocarcinogenesis. Immunohistochemistry
      revealed that TGF-beta1-positive preneoplastic hepatocytes increased with time,
      and that this correlated with a reduction TGR2 expressing preneoplastic lesions.
      Hepatocellular carcinoma (HCC) tissues showed higher levels of TGF-beta1
      transcripts and protein and lower levels of TGR2 transcripts and protein compared
      to the paired adjacent liver parenchyme. TUNEL revealed that apoptotic cells
      increased with time and were more numerous in the adjacent liver parenchyme than
      in preneoplastic lesions and HCC tissues. Our data suggest that the down
      regulation of TGR2 in preneoplastic lesions and HCC tissues might contribute to
      resistance to the growth inhibitory effects of TGF-beta1, and to the roles of TGF
      beta1 in the development and progression of preneoplastic lesions and HCC in a
      chemically induced rat hepatocarcinogensis model.

PMID- 14585398
TI  - Low density lipoprotein receptor-related protein (LRP) is a heparin-dependent
      adhesion receptor for connective tissue growth factor (CTGF) in rat activated
      hepatic stellate cells.
AB  - Connective tissue growth factor (CTGF) is a cysteine-rich, extracellular matrix
      associated heparin-binding protein implicated in a variety of fibrotic disorders.
      CTGF is initially synthesized as a mosaic protein containing four discrete
      structural modules (CTGF(1-4)) but this is susceptible to proteolytic cleavage
      yielding isoforms comprising modules 3 and 4 (CTGF(3-4)) or module 4 alone
      (CTGF(4)). In this study, we show that cultured rat hepatic stellate cells (HSCs)
      produce CTGF(1-4) and CTGF(3-4) following treatment with transforming growth
      factor-beta and that CTGF is a cell adhesion factor for activated HSCs. Low
      density lipoprotein receptor-associated protein (LRP) is a receptor for CTGF(1-4)
      or CTGF(3-4), but not CTGF(4), whereas cell surface heparan sulfate proteoglycans
      (HSPGs) are binding sites for all CTGF isoforms. Prior occupancy of LRP with
      other LRP ligands, receptor associated protein, anti-LRP, or a thrombospondin
      type I peptide (TEWSACSKTCG) resulted in a 50% decrease in the adhesion of
      activated HSCs to CTGF(1-4) or CTGF(3-4) whereas there was no effect on CTGF(4)
      mediated adhesion. Co-incubation of CTGF with heparin or perturbation of cell
      surface HSPGs with heparinase or sodium chlorate completely blocked adhesion of
      activated HSCs to all CTGF isoforms. Freshly isolated HSCs demonstrated only weak
      binding to CTGF but strong binding to fibronectin. Thus HSC adhesion is at least
      partially promoted by CTGF through its binding to LRP, a process that is heparin
      dependent. CTGF-LRP interactions are likely mediated by module 3 and CTGF-heparin
      interactions occur principally in module 4, although additional motifs may
      account for the heparin-dependency of LRP binding. These data show that LRP and
      HSPGs are utilized by HSCs for binding to CTGF and suggest that these cell
      surface molecules may be involved in mediating CTGF activity or adhesive
      signaling during the activation process.

PMID- 14585399
TI  - Gender-related differences in concanavalin A-induced liver injury and cytokine
      production in mice.
AB  - BACKGROUND/AIM: Concanavalin A (Con A) activates T cells and causes T cell
      mediated liver injury in mice. Since autoimmune diseases predominantly occur in
      women, female is considered to have enhanced immune responses and T cell
      functions. We investigated the presence of gender-related differences on Con A
      induced liver injury and cytokine production in mice. METHODS: Male and female
      BALB/c mice were given Con A (15mg/kg) intravenously at 7 weeks of age. Plasma
      alanine aminotransferase (ALT), tumor necrosis factor alpha (TNF-alpha),
      interferon gamma (IFN-gamma), interleukin (IL)-4 and IL-10 levels were determined
      0, 2, 4, 6, 8 and 24h after Con A administration. To investigate the effects of
      sex hormones on liver injury and cytokine production, female and male mice were
      castrated at 3 weeks of age and were administered Con A 4 weeks after the
      operation. RESULTS: Plasma ALT level of females was significantly higher at 8 and
      24h after Con A administration than those of males. Plasma levels of TNF-alpha
      and IFN-gamma at 2, 4, 6 and 8h, IL-4 at 2h, but not IL-10, after Con A
      administration were significantly elevated in females than those of males.
      Furthermore, the elevated plasma ALT, TNF-alpha and IFN-gamma levels decreased
      significantly by an ovariectomy. In contrast, those markers were exacerbated by
      an orchiectomy compared with sham operation. CONCLUSION: These findings indicate
      that Con A induces more severe liver injury in female mice than in male mice, and
      suggest that the effect of sex hormones on cytokine production may play a role in
      gender-related difference on Con A-induced liver injury.

PMID- 14585400
TI  - Amino acid ratios in plasma and tissues in a rat model of liver cirrhosis before
      and after exercise.
AB  - In human liver cirrhosis (LC), the Fischer ratio (branched-chain amino acid
      (BCAA)/aromatic amino acid (AAA)) is used as a marker of hepatic encephalopathy.
      Similarly, the plasma BCAA levels decrease while AAA levels increase in LC rats.
      However the BCAA and AAA ratio and the influence of exercise on this ratio
      remains to be clarified in various tissues of the LC rat model. Normal and LC
      rats received 2-weekly injections of olive oil or CCl(4) for 10 weeks,
      respectively, and half of the rats from each group were subjected to one time
      exercise on a treadmill. BCAA, AAA, glutamate (GLU) and glutamine (GLN)
      concentrations were measured in plasma, liver, brain, heart and skeletal muscles.
      Decreased BCAA and increased AAA concentrations in brain and heart were also
      observed in LC rats and these changes were significantly amplified by exercise.
      The Fischer ratio in the LC group with and without exercise was decreased in
      skeletal muscles, while it remained unchanged in the liver. Decreased GLU and
      increased GLN concentrations were shown in most LC samples following exercise. In
      conclusion, specific alterations of the amino acid patterns were observed in
      various tissues in the LC group. These alterations were further emphasized by
      exercise.

PMID- 14585401
TI  - Heterogeneity of rat liver parenchyma in taurocholate uptake.
AB  - Periportal and perivenous hepatocytes were isolated from rat liver by
      digitonin/collagenase perfusion for investigating the acinar distribution of
      taurocholate uptake. Statistical analysis revealed that uptake of taurocholate by
      periportal, perivenous and regular (whole acinus) hepatocytes in Na(+)-containing
      and -free buffer was best described by one saturable component. Total
      taurocholate uptake measured in Na(+)-containing buffer was significantly higher
      in perivenous (V(max)=7.5 nmol/(min mg protein)) than in periportal hepatocytes
      (V(max)=5.4 nmol/(min mg protein)). Uptake by regular hepatocytes was well
      between the values of periportal and perivenous hepatocytes (V(max)=6.7 nmol/(min
      mg protein)). The K(m)-values were not different among the zonal regions. In
      Na(+)-free buffer, K(m) and V(max) of taurocholate uptake calculated for all
      fractions were similar. During cultivation of hepatocytes as monolayer total
      taurocholate uptake strongly decreased and the zonal differences observed in
      freshly isolated cells in suspension disappeared. Initial uptake rates of Na(+)
      independent taurocholate uptake and the ATP-content of the hepatocytes were
      constant. Our results indicate an acinar gradient of Na(+)-dependent taurocholate
      uptake activity, which may improve the clearance of bile salts from portal blood
      and protect periportal hepatocytes against a too high intracellular bile salt
      concentration.

PMID- 14585402
TI  - Fulminant hepatic failure in a patient with inactive HBsAg carrier state, acute
      hepatitis E and thyrotoxicosis.
AB  - A 38-year-old man presented with jaundice and significant weight loss.
      Investigations found positive hepatitis B surface antigen (HBsAg). His hepatitis
      B e antigen (HBeAg) was negative and HBV DNA was not detectable in the blood.
      Further tests revealed that he also had acute hepatitis E infection and
      uncontrolled thyrotoxicosis. The hypercatabolic state of coexisting
      thyrotoxicosis and acute hepatitis caused marked weight loss and clinical
      deterioration with fulminant hepatic failure. Institution of successful anti
      thyroid treatment and supplemental nutrition effectively reversed the disease
      progression and the patient recovered fully.

PMID- 14585403
TI  - Mortality risk after head injury increases at 30 years.
AB  - BACKGROUND: Age has long been recognized as a critical factor in predicting
      outcomes after head injury, with individuals older than 60 years predicted to
      have a worse outcome than those younger than 60. The object of this study was to
      determine the effect of age by decade of life beginning at birth in patients with
      head injuries of all levels of severity. STUDY DESIGN: The New York State Trauma
      Registry was searched for head injuries from January 1, 1994 to December 31,
      1995; the 13,908 cases found were placed into age groups by decade. Data were
      sought for each patient on demographics, Glasgow Coma Score, ICD-9 injury code,
      New Injury Severity Score (NISS), and mechanism of injury. These data were
      analyzed with chi-square and one-way ANOVA tests, with significance set at p <
      0.05. RESULTS: The risk of dying was significantly increased in patients
      beginning at 30 years of age compared with those in the younger age groups, with
      the greatest increases occurring after age 60 (p < 0.001). For the population
      with available Glasgow Coma Score data (n = 12,844), the mortality rate for
      patients ages 0 to 30 was 10.9%, and for patients ages 31 to 50 was 12.4%. The
      mean Glasgow Coma Score for nonsurvivors ages 0 to 20 (3.9) and for nonsurvivors
      ages 31 to 50 (5.1) were significantly different, with a risk ratio of 1.3 (p <
      0.001). CONCLUSIONS: The risk of dying for patients suffering head injuries
      increases as early as 30 years of age, making it necessary for health-care
      providers to consider increased monitoring and treatment for patients in this
      younger age group.

PMID- 14585404
TI  - Fractures in access to and assessment of trauma systems.
AB  - BACKGROUND: Trauma is a major public health problem and organized systems of
      trauma care have been shown to substantially reduce trauma-related mortality.
      Currently California and many other states have incompletely developed systems of
      trauma care delivery. This study was undertaken to determine how frequently
      patients incurring serious trauma in California receive treatment at a trauma
      center. STUDY DESIGN: Hospital discharge records for 360,743 acute trauma
      patients for 1995 to 1997 were analyzed. Abbreviated Injury Scale scores were
      calculated from discharge diagnosis codes. Severity of trauma and the need for
      trauma center treatment was defined by eight Abbreviated Injury Scale criteria
      combined with patient age and type of injury. RESULTS: According to study
      criteria, 67,718 patients needed trauma center care and 56% were treated at a
      trauma center. Among patients less than 55 years of age, 62% were treated at a
      trauma center compared with 40% of those aged 55 years or more (p < 0.0001). For
      patients less than 55 years old with brain injuries, 66% were treated at a trauma
      center compared with 44% for patients aged 55 years or more (p < 0.0001). Of the
      29,849 patients who met Abbreviated Injury Scale criteria but were not treated at
      trauma centers, 59% were in counties with designated trauma centers and 41% were
      in counties without trauma centers. CONCLUSIONS: Only 56% of seriously injured
      patients in California were treated at trauma centers, despite most of the
      injuries occurring in the catchment areas of designated trauma care systems.
      Substantial undertriage of serious trauma patients to trauma centers appears to
      be occurring, especially in older persons and in persons with brain injuries.
      Efforts to understand why undertriage is occurring so frequently are hampered by
      fragmentation of the systems of care, inadequate data management systems, and
      lack of trauma care performance reporting by non-trauma center hospitals.

PMID- 14585405
TI  - Breast conservation in patients with multiple ipsilateral synchronous cancers.
AB  - BACKGROUND: Because breast cancer survival after breast conservation has proved
      comparable to mastectomy, contraindications to mastectomy are increasingly being
      challenged. We treated the majority of our patients with multiple synchronous
      ipsilateral cancers with breast conservation and we compared them with patients
      who underwent mastectomy for comparable disease during the same interval. STUDY
      DESIGN: Patients with multiple ipsilateral synchronous breast cancers between
      1989 and 2002 were identified from prospective databases maintained by us. A
      comparison was made between 36 patients treated with lumpectomy and 19 patients
      treated with mastectomy. RESULTS: There were no significant (all p values >0.2)
      differences between mastectomy and breast conservation patients in age, racial
      distribution, size of cancers, pathology, tumor differentiation, nodal
      involvement, or hormone receptor positivity. The majority of patients treated
      with breast conservation underwent at least one reexcision to obtain clear
      pathologic margins, and they were more likely to receive postoperative
      radiotherapy than patients treated with mastectomy. There were no significant
      differences in the local (97% versus 100%, p = 0.54) or distant (97% versus 95%,
      p = 0.20) 5-year disease- free survival between the group treated with breast
      conservation and the group treated with mastectomy. One patient in each group
      developed distant metastases. One patient in the breast conservation group
      developed local recurrence at both primary sites simultaneously 39 months after
      lumpectomies. She is free of disease 78 months after mastectomy. The remaining 52
      patients are alive and free of disease. CONCLUSIONS: Breast conservation is an
      effective treatment for patients with synchronous ipsilateral breast cancers.

PMID- 14585406
TI  - Multimodality management of hepatocellular carcinoma larger than 10 cm.
AB  - BACKGROUND: Hepatic resection for huge hepatocellular carcinoma (HCC) is
      challenging. The role of multimodality nonsurgical therapy for HCC larger than 10
      cm is unclear. STUDY DESIGN: We retrospectively investigated 131 HCC patients
      with main tumors larger than 10 cm in diameter seen between October 1990 and
      October 2001. Fifty-six patients (group A) underwent hepatectomy and 75 patients
      (group B) underwent nonsurgical multidisciplinary therapy including hepatic
      arterial infusion, transcatheter arterial embolization, and percutaneous acetic
      acid injection. RESULTS: Patients in group B were older, had lower serum albumin
      levels, and there were more patients with liver cirrhosis and great vessel
      invasion. Median survivals of group A and B patients were 17 months and 7 months,
      respectively (p < 0.001). But the 1-, 3-, 5-year survival rates in group B using
      38 patients undergoing 3 or more sessions of nonsurgical treatment were not
      significantly worse than those for group A using 53 patients with followup
      (57.1%, 19.0%, 16.3% versus 60.7%, 24.5%, 24.5%, respectively). Group A patients
      had 37.7% and 71.7% recurrence rates at 6 and 12 months, respectively, after
      operation, and they had a significantly higher frequency of overall extrahepatic
      recurrence compared with group B patients (43.4% versus 18.7%, p = 0.005). In
      group B, only 3 of 35 patients younger than 60 years had tumor shrinkage after
      nonsurgical treatment modalities in comparison to 17 of 40 patients in the
      elderly group (p = 0.003). Younger patients had a significantly higher prevalence
      of hepatitis B surface antigen positivity (85.7% versus 47.5%) and infiltrating
      tumor growth pattern (74.3% versus 45.0%) compared with older patients.
      CONCLUSIONS: Our study suggests that the advantage of hepatic resection in
      patients with huge HCC is marginal. An effective adjuvant therapy is needed to
      improve outcomes after hepatic resection. The experience in using nonsurgical
      treatment shows that the result is poor in young patients compared with that in
      elderly patients.

PMID- 14585407
TI  - Accuracy of preoperative localization studies and intraoperative parathyroid
      hormone assay in patients with primary hyperparathyroidism and double adenoma.
AB  - BACKGROUND: The purpose of this retrospective investigation was to evaluate the
      results of preoperative localization studies and intraoperative parathyroid
      hormone (IOPTH) assay in patients with primary hyperparathyroidism and double
      adenomas. STUDY DESIGN: Twenty-one of 287 consecutive patients with primary
      hyperparathyroidism who had double adenomas identified during first-time
      parathyroid exploration between July 1999 and September 2002 were analyzed.
      Individual and combined accuracy of preoperative localization studies, and IOPTH
      assay and their influence on surgical strategy, were compared. RESULTS: Seven
      percent of these 287 patients had double adenomas. Fifteen of the patients were
      female and six were male with a mean age of 59 years (range 17 to 76 years). The
      accuracy of ultrasonography (US) and technetium 99m sestamibi ((99m)TC-sestamibi)
      was 40% and 30%, respectively, in this select group. Combined accuracy of both
      tests reached 60% and guided the surgeon to select a bilateral approach. After
      removal of the first gland, IOPTH failed to decrease by 50% relative to the
      highest baseline value in 43% of the cases, indicating other hyperfunctioning
      parathyroid glands. These results prompted the surgeon to explore further after
      an initially planned focused approach. When the combination of three tests was
      analyzed, at least one test accurately suggested a double adenoma in 80% of the
      patients; in 15% of the patients, no test was suggestive of a double adenoma and
      in 5% the sestamibi scan was false positive. CONCLUSIONS: This retrospective
      investigation documents that neither preoperative localization tests nor IOPTH
      assay accurately document double adenomas in patients with primary
      hyperparathyroidism. The combined accuracy of US, sestamibi, and IOPTH assay
      predicted a double adenoma in 80% of the patients.

PMID- 14585408
TI  - Benefits of early feeding and early hospital discharge in elderly patients
      undergoing open colon resection.
AB  - BACKGROUND: Recent studies have demonstrated a reduction in hospital stay and
      postoperative complications in elderly patients undergoing laparoscopy-assisted
      colectomy, and have attributed the shorter stays and reduced morbidity to the
      laparoscopic approach. We questioned whether the improved outcomes in these
      studies were a result of the laparoscopic procedure alone or a result of early
      postoperative feeding and early hospital discharge. We hypothesized that early
      feeding in elderly patients undergoing open colorectal resection results in a
      short hospital stay and favorably affects postoperative morbidity. STUDY DESIGN:
      Patients aged 70 years and older who were undergoing elective open colon
      resection were placed on an early postoperative feeding protocol. The early
      feeding protocol consisted of clear liquids on postoperative day 2, regular diet
      on postoperative day 3, and discharge to home as tolerated. The main outcomes
      measurements included early feeding tolerance, hospital stay, postoperative
      morbidity, and requirement for postoperative assisted care. RESULTS: There were
      87 study patients (42 men and 45 women, mean age 77 years). The most common
      operation was right hemicolectomy (53%). Overall 78 of 87 patients (89.6%)
      tolerated early feeding. Five patients (5.7%) initially tolerated a diet but
      required readmission for ileus. Nine patients (10.4%) did not tolerate early
      feeding initially. The mean hospital stay for all patients was 3.9 days. There
      were 15 postoperative complications in 13 patients (14.9%), the most common of
      which was urinary retention. There were no deaths, anastomotic leaks, abscesses,
      or pneumonia. Only 3 of 86 patients (3.5%) who were previously independent
      required assisted care after colectomy. CONCLUSIONS: In elderly patients
      undergoing elective open colon resection, early feeding results in a short
      hospital stay and low postoperative morbidity. These results are comparable to
      those reported for laparoscopy-assisted colectomy.

PMID- 14585409
TI  - Predictors and patterns of recurrence after resection of hepatocellular
      carcinoma.
AB  - BACKGROUND: The majority of patients with hepatocellular carcinoma (HCC) who
      undergo complete tumor resection subsequently develop tumor recurrence. The
      objectives of this study were to determine the risk factors for recurrence of HCC
      after hepatectomy and to examine the outcomes once tumor recurrence occurs. STUDY
      DESIGN: From February 1990 to May 2001 a total of 164 patients underwent liver
      resection for HCC at our institution and were prospectively followed. Time to
      recurrence and survival after recurrence were determined by Kaplan-Meier
      analysis. Patient, tumor, and treatment characteristics were tested for their
      prognostic significance by univariate and multivariate analysis using the logrank
      test and the Cox proportional hazards model, respectively. RESULTS: The median
      patient age was 64 years (range 21 to 87 years) and 106 patients (65%) were male.
      After a median followup of 26 months, 90 patients (55%) have developed recurrent
      cancer. Among them, 75 patients (83%) had tumor detectable in the liver, which
      was the only site of disease in 67 (74%). In all, 15 patients (20%) had
      extrahepatic disease (7 lung, 4 peritoneum, 2 pancreas, 1 bone, and 1 brain). The
      median time to recurrence was 24 months (range 1 to 274 months). Predictors of
      recurrence on univariate analysis were tumor size greater than 5 cm, more than
      one tumor, cirrhosis, vascular invasion (microscopic or macroscopic), and tumor
      satellites. On multivariate analysis only tumor size greater than 5 cm (p = 0.04)
      and vascular invasion (p = 0.01) predicted recurrence. The median survival after
      recurrence was 11 months (range 0 to 60 months). Of the 90 patients who developed
      tumor recurrence 49 (67%) were able to undergo additional ablative or surgical
      therapy (33 embolization, 9 ethanol injection, and 14 re-resection). On
      multivariate analysis vascular invasion in the original tumor predicted poor
      survival after recurrence (p = 0.009). CONCLUSIONS: The liver is the predominant
      site of first recurrence after resection of hepatocellular carcinoma, and once
      recurrence occurs survival is limited. The current study underscores the need for
      effective adjuvant therapy for patients with HCC treated with partial
      hepatectomy.

PMID- 14585410
TI  - Locoregional recurrences are frequent after radiofrequency ablation for
      hepatocellular carcinoma.
AB  - BACKGROUND: Enthusiasm for radiofrequency ablation (RFA) therapy for patients
      with unresectable hepatocellular carcinoma (HCC) has increased. The data for
      recurrence after RFA for patients with HCC is not well documented. The purpose of
      this study was to evaluate tumor recurrence patterns after RFA in patients with
      unresectable HCC. STUDY DESIGN: Over a 3-year period, 50 patients having RFA for
      unresectable HCC were identified at a single institution. Medical records and
      radiologic studies were reviewed and outcomes factors analyzed. RESULTS: Of the
      entire cohort, 46 patients underwent RFA by a percutaneous approach under CT
      guidance. Most patients underwent either one (n = 22) or two ablations (n = 23).
      At the time of this report, 14 patients (28%) were tumor-free by radiologic and
      biochemical (alpha-fetoprotein) parameters. Eighteen additional patients had
      persistence of tumor at the ablation site and 14 patients had recurrence in the
      liver at sites different from the ablation site. An additional four patients had
      recurrence in extrahepatic sites. Twelve patients underwent orthotopic liver
      transplantation after RFA. Of these 12, 5 (42%) demonstrated no viable tumor in
      the explanted liver. Independent predictors of tumor recurrence included tumor
      size, serum AFP levels, and the presence of hepatitis. CONCLUSIONS: These data
      suggest that factors such as tumor size should be considered before employing RFA
      therapy. In addition to treating the primary tumor, other therapies aimed at the
      liver's inflammatory state might also be important in achieving a durable
      response after RFA.

PMID- 14585411
TI  - Combined adult-to-adult living donor right lobe liver transplantation and
      pancreatoduodenectomy for distal bile duct adenocarcinoma in a patient with
      primary sclerosing cholangitis.
AB  - BACKGROUND: Liver transplantation is the best therapeutic option for patients
      with end-stage liver disease from primary sclerosing cholangitis. Primary
      sclerosing cholangitis is associated with a markedly increased risk of
      cholangiocarcinoma, which adversely affects survival. Approximately 20% to 30% of
      cholangiocarcinomas are localized in the distal bile duct. Pancreatoduodenectomy
      is the curative therapy for cholangiocarcinomas in this location. STUDY DESIGN:
      We reviewed our data on a patient with primary sclerosing cholangitis-related end
      stage liver disease and a simultaneous distal bile duct tumor, which was treated
      with a combined right-lobe, living-donor liver transplantation and
      pancreatoduodenectomy. RESULTS: The patient was discharged 32 days post
      transplantation. He is currently alive 1 year after the procedure with no
      evidence of recurrent cancer. CONCLUSIONS: Combined living-donor liver
      transplantation and pancreatoduodenectomy is feasible and allows timely and
      elective surgical control of carefully selected distal bile duct tumors in the
      setting of end-stage liver disease.

PMID- 14585412
TI  - Partial abdominal evisceration, ex vivo resection, and intestinal
      autotransplantation for the treatment of pathologic lesions of the root of the
      mesentery.
AB  - BACKGROUND: Resection of lesions of the root of the mesentery with established
      techniques is difficult and at times impossible because of their proximity to the
      blood supply of the intestine. Damage of the superior mesenteric vessels
      necessitates resection of the intestine, resulting in short bowel syndrome and
      intestinal failure. STUDY DESIGN: We describe a surgical technique drawn from our
      experience in intestinal transplantation in which the root of the mesentery
      (including the lesion) and the head or the entire pancreas, duodenum, small
      intestine, and part of the colon are excised en bloc and preserved in a cold
      solution. Resection of the lesion is performed in a bloodless field ex vivo, and
      the salvaged intestine is reimplanted in the abdominal cavity. We performed this
      procedure in four patients, two adult and two pediatric, who had extensive
      neoplasms of the root of the mesentery. Their underlying diseases were mesenteric
      fibroma, vascular dysplasia of the root of the mesentery, pancreatic cancer, and
      desmoid tumor. RESULTS: Local control of the lesions was achieved in all four
      cases, preserving at the same time enough small intestine to avoid short bowel
      syndrome. All patients survived the operation and live on enteral nutrition 6 to
      49.5 months after the procedure. CONCLUSIONS: The procedure of partial abdominal
      exenteration, ex vivo resection, and autotransplantation is an extension of our
      experience with intestinal transplantation. In selected cases, this technique may
      be useful in the treatment of extensive, otherwise unresectable lesions of the
      root of the mesentery.

PMID- 14585413
TI  - Thoracoscopic approach for spine deformities.
AB  - BACKGROUND: We reviewed our experience using anterior thoracoscopic procedures in
      the correction of severe idiopathic scoliosis and kyphotic deformities to
      evaluate the feasibility and effectiveness of such procedures. STUDY DESIGN:
      Twenty-four patients who underwent thoracoscopic surgical correction of the spine
      between March 1995 and December 2001 were retrospectively reviewed. A team
      consisting of one orthopaedic surgeon and one thoracic surgeon performed anterior
      thoracoscopic soft tissue release, disc excision, and bone grafting followed on
      the same day with posterior instrumentation and correction of deformity. RESULTS:
      There were 16 female and 8 male patients, with a median age of 16 years (range 11
      to 47 years) with idiopathic scoliosis (20 patients) or kyphotic deformity (4
      patients). The average time for the thoracoscopy was 125 minutes (range 60 to 175
      minutes). Blood loss averaged 135 mL (range 20 to 350 mL), and a median number of
      five discs (range two to eight) were excised. The median ICU time was 2 days
      (range 1 to 8 days), and the median length of hospital stay was 6 days (range 4
      to 11 days). One patient required conversion to an open procedure because of
      arterial bleeding from the cancellous bone (T5). Postoperative complications
      occurred in four patients (atelectasis, pneumothorax, pneumonia, and wound
      infection in one patient each). All patients had an uneventful hospital course
      after treatment. CONCLUSIONS: Thoracoscopic anterior procedures can be used
      safely and effectively in the treatment of idiopathic scoliosis and kyphotic
      deformity. This minimally invasive approach might decrease procedure-related
      trauma, operative time, blood loss, and length of hospitalization and may also
      alleviate postthoracotomy pain.

PMID- 14585414
TI  - Factors affecting intravenous analgesic requirements after colectomy.
AB  - BACKGROUND: The purpose of this study was to determine factors that influence
      postoperative IV analgesic use after colectomy. STUDY DESIGN: We retrospectively
      evaluated patients who underwent colectomy between January 1997 and December 2000
      at our medical center and calculated the amount of postoperative IV narcotics
      needed in morphine equivalents. Statistical differences (p < 0.05 considered
      significant) were measured using the Wilcoxon rank-sum test. Correlations were
      performed using Spearman correlation coefficients, and linear regression analysis
      was also performed. RESULTS: Four hundred eighty-one patients (235 men, 246
      women) underwent colectomy; patients had a mean age of 60.6 years (range, 17 to
      96 years). Procedures performed included total/subtotal colectomy (10%, n = 49),
      right colectomy (42%, n = 200), transverse colectomy (3%, n = 12), left/sigmoid
      colectomy (40%, n = 195), and low anterior resection (4%, n = 17). Laparoscopic
      colectomy was performed in 53 (11%) patients. Mean postoperative morphine
      equivalent use was 160.2 mg. Narcotic analgesic use was significantly less for
      women (p = 0.02), diagnosis of cancer (p = 0.02), and laparoscopic colectomy (p =
      0.0001). Patients undergoing a right colectomy required less postoperative
      narcotics than patients having other types of colectomies (p < 0.02). There was a
      positive correlation between postoperative narcotic use and operative time (r =
      0.14, p = 0.007) and a negative correlation with patient age (r = -0.37, p =
      0.0001). Linear regression analysis demonstrated that age (p = 0.0001), female
      gender (p = 0.04), and laparoscopy (p = 0.001) were independent predictors for
      decreased narcotic use. CONCLUSIONS: Postoperative IV narcotic analgesic use is
      affected by gender, patient age, indication for colectomy, operative time, type
      of procedure, and operative technique.

PMID- 14585415
TI  - Phosphocreatine restores high-energy phosphates in ischemic myocardium:
      implication for off-pump cardiac revascularization.
AB  - BACKGROUND: High-energy phosphate metabolism is altered in the ischemic
      myocardium. We investigated the effects of in vivo administration of
      phosphocreatine (PCr) in a transient ischemic rat model to emulate off-pump
      myocardial revascularization. STUDY DESIGN: Rats received either PCr (100 mg/kg)
      or saline intravenously 1 hour before surgery. Regional ischemia was maintained
      for 12 minutes by ligation of the left anterior descending artery and compared
      with sham-operated animals. Cardiac tissue was studied for ATP, PCr, and
      inorganic phosphate (Pi) using (31)P-cryo-NMR. Results were compared by ANOVA.
      RESULTS: Levels of ATP were significantly (p < 0.01) lower in the ischemic hearts
      compared with controls; Pi and PCr remained unchanged. The PCr/Pi ratio was
      altered in ischemic hearts, reflecting an increased energy demand. PCr
      administration significantly (p < 0.01) elevated the content of PCr and ATP in
      both normal and ischemic hearts. CONCLUSIONS: PCr restores high-energy phosphates
      and attenuates metabolic stress during periods of myocardial ischemia in the rat.
      Preconditioning with PCr may serve as a useful adjunct to off-pump coronary
      revascularization.

PMID- 14585416
TI  - What's new in surgery: gastrointestinal conditions.

PMID- 14585417
TI  - What's new in ophthalmic surgery?

PMID- 14585418
TI  - Hospital discharge to other healthcare facilities: impact on in-hospital
      mortality.
AB  - BACKGROUND: In-hospital mortality is frequently used as an outcomes measure for
      surgical procedures. Recently, hospitals have developed subacute care facilities
      to allow earlier discharge. Outcomes of patients discharged (transferred) to
      these units or to other similar facilities may not be captured in reports of in
      hospital mortality. STUDY DESIGN: The California Office of Statewide Health
      Planning and Development (OSHPD) patient discharge abstract database was examined
      to determine the rates of discharge to other facilities (transfer) and the number
      of in-hospital deaths occurring during the index hospitalization and after
      transfer in patients undergoing cardiac surgery procedures. Data were collected
      for 1997, 1998, and 1999 for coronary artery bypass grafting (CABG-only, n =
      82,897), CABG plus additional procedures (CABG-plus, n = 11,869), and valve
      repair or replacement (Valve-only, n = 14,872). In-hospital mortality and
      transfer rates (same-day discharge and readmission to another facility) were
      determined for all hospitals through the index hospitalization and subsequent
      transfers. RESULTS: Aggregated 3-year in-hospital mortality rates for the index
      hospitalization were 2.98% for CABG-only, 9.25% for CABG-plus, and 4.85% in Valve
      only groups. Transfer rates were 12.41%, 23.16%, and 13.43%, respectively. The
      percentages of all in-hospital deaths occurring after transfer from the index
      hospital were 13.5% (385 of 2,857) in CABG-only, 13.3% (168 of 1,266) in CABG
      plus, and 11.0% (89 of 811) in Valve-only patients. When corrected for these
      additional deaths, the actual in-hospital mortality rate was 3.45% for CABG-only,
      10.67% for CABG-plus, and 5.45% for Valve-only procedures. CONCLUSIONS: Transfer
      to another healthcare facility rather than discharge home is a common practice
      after cardiac surgery. A substantial percentage of in-hospital deaths occurs
      after discharge from the primary institution.

PMID- 14585420
TI  - The role of genetics in the surgical management of familial endocrinopathy
      syndromes.

PMID- 14585421
TI  - Complications in pediatric surgical oncology.

PMID- 14585422
TI  - Lister and Osler: comparisons, contrasts, and connections.

PMID- 14585423
TI  - The surgical intensivist as mediator of end-of-life issues in the care of
      critically ill patients.

PMID- 14585425
TI  - Statement on disaster and mass casualty management.

PMID- 14585426
TI  - Disaster and mass casualty management: a commentary on the American College of
      Surgeons position statement.

PMID- 14585428
TI  - Bile duct injury after laparoscopic cholecystectomy: resection of the entire
      extrahepatic biliary tree.

PMID- 14585427
TI  - Multiple hemangiomas of the appendix and liver.

PMID- 14585429
TI  - Laparoscopic antrectomy: a novel approach to treating watermelon stomach.

PMID- 14585430
TI  - Balloon repositioning of intrathoracic upside-down stomach and fixation by
      percutaneous endoscopic gastrostomy.

PMID- 14585431
TI  - Early results using a dynamic method for delayed primary closure of fasciotomy
      wounds.

PMID- 14585432
TI  - Retrorectal cysts.

PMID- 14585433
TI  - Zuckerkandl's tubercle: Hannibal ad Portas.

PMID- 14585434
TI  - Barrett's esophagus.

PMID- 14585436
TI  - Climbing the cortical ladder from sensation to perception.
AB  - A recent study using displays that are ambiguous for motion direction
      demonstrates that the current perceptual interpretation of such a stimulus is
      encoded in the highest areas of visual cortex whereas earlier areas encode only
      its sensory properties. This finding implies that cortical processing pathways
      perform a transition from a sensory representation to a representation that
      emphasizes the input's perceptual interpretation and ultimately the organism's
      behavioral state.

PMID- 14585437
TI  - Wholes, holes, and basic features in vision.
AB  - A key issue for theories of perception is specifying the primitives used by the
      visual system to isolate and identify the objects in an image. Although local
      features are typically suggested, there is good reason to look for global,
      configural features as primitives too. Chen et al.'s specific proposal of
      topological features is both explicit and capable of capturing important global
      information. It may seem surprising that topology can be detected by honeybees,
      but Chen's results are in keeping with other findings from humans that global
      properties are sometimes perceived better than local ones and thus might be
      basic.

PMID- 14585438
TI  - Statistical decision theory and evolution.
AB  - Two recent articles by Geisler and Diehl use Bayesian statistical decision theory
      to model the co-evolution of predator and prey in a simple, game-like
      environment. The prey is characterized by its coloration. The predator is
      characterized by the chromatic sensitivity of its visual system and its
      willingness to attack. The authors demonstrate how the coloration of prey and the
      perceptual system of the predator co-evolve, converging to a Nash equilibrium for
      both species.

PMID- 14585442
TI  - Weighing up the facts of category-specific semantic deficits.

PMID- 14585444
TI  - A theory of magnitude: common cortical metrics of time, space and quantity.
AB  - Research into the perception of space, time and quantity has generated three
      separate literatures. That number can be represented spatially is, of course,
      well accepted and forms a basis for research into spatial aspects of numerical
      processing. Links between number and time or between space and time, on the other
      hand, are rarely discussed and the shared properties of all three systems have
      not been considered. I propose here that time, space and quantity are part of a
      generalized magnitude system. I outline A Theory Of Magnitude (ATOM) as a
      conceptually new framework within which to re-interpret the cortical processing
      of these elements of the environment.

PMID- 14585445
TI  - Measuring word recognition in reading: eye movements and event-related
      potentials.
AB  - The investigation of visual word recognition has been a major accomplishment of
      cognitive science. Two on-line methodologies, eye movements and event-related
      potentials, stand out in the search for the holy grail - an absolute time measure
      of when, how and why we recognize visual words while reading. Although each
      technique has its own experimental limitations, we suggest, by means of review
      and comparison, that these two methodologies can be used in complementary ways to
      produce a better picture of the mental action we call reading.

PMID- 14585446
TI  - Primate cognition: from 'what now?' to 'what if?'.
AB  - The 'social brain' hypothesis has had a major impact on the study of comparative
      cognition. However, despite a strong sense, gained from both experimental and
      observational work, that monkeys and apes differ from each other, we are still no
      closer to understanding exactly how they differ. We hypothesize that the
      dispersed social systems characteristic of ape societies explains why monkeys and
      apes should differ cognitively. The increased cognitive control and analogical
      reasoning ability needed to cope with life in dispersed societies also suggests a
      possible route for human cognitive evolution. This hypothesis is supported by
      behavioural and neurobiological data, but we need more of both if we are to fully
      understand how our primate cousins see the world.

PMID- 14585447
TI  - Human gaze control during real-world scene perception.
AB  - In human vision, acuity and color sensitivity are best at the point of fixation,
      and the visual-cognitive system exploits this fact by actively controlling gaze
      to direct fixation towards important and informative scene regions in real time
      as needed. How gaze control operates over complex real-world scenes has recently
      become of central concern in several core cognitive science disciplines including
      cognitive psychology, visual neuroscience, and machine vision. This article
      reviews current approaches and empirical findings in human gaze control during
      real-world scene perception.

PMID- 14585448
TI  - Artificial life: organization, adaptation and complexity from the bottom up.
AB  - Artificial life attempts to understand the essential general properties of living
      systems by synthesizing life-like behavior in software, hardware and
      biochemicals. As many of the essential abstract properties of living systems
      (e.g. autonomous adaptive and intelligent behavior) are also studied by cognitive
      science, artificial life and cognitive science have an essential overlap. This
      review highlights the state of the art in artificial life with respect to
      dynamical hierarchies, molecular self-organization, evolutionary robotics, the
      evolution of complexity and language, and other practical applications. It also
      speculates about future connections between artificial life and cognitive
      science.

PMID- 14585449
TI  - The GI Cocktail is no more effective than plain liquid antacid: a randomized,
      double blind clinical trial.
AB  - The "GI Cocktail" is a mixture of medications often given in the Emergency
      Department (ED) for dyspepsia symptoms. Several combinations are used, but the
      most effective has not yet been determined. This study compared three
      combinations commonly given for dyspepsia. The study was a prospective,
      randomized, double-blinded trial comparing antacid (group 1); antacid + Donnatal
      (group 2); antacid + Donnatal + viscous lidocaine (group 3) for acute treatment
      of dyspepsia in the ED. Patients were randomly assigned to receive one of the
      three medication combinations. Patients rated their discomfort on a Visual Analog
      Scale (VAS) immediately before receiving the medication and 30 min later. Change
      in VAS was the primary study endpoint. A 13-mm difference in VAS was considered
      clinically significant. VAS change in the three groups was compared using
      multivariable regression, controlling for pretreatment VAS, study drug, previous
      antacid use, and gastrointestinal (GI) history. One hundred twenty patients were
      enrolled between July and December 2000. One hundred thirteen subjects (113)
      completed the protocol: Group 1 (N = 38); Group 2 (N = 37); Group 3 (N = 38).
      There was no statistically significant difference between the groups in terms of
      age, gender, GI history, previous antacid use, or initial degree of pain. Group 1
      had a 25 +/- 27 mm mean (+/- SD), decrease in pain; Group 2, 23 +/- 22 mm
      decrease; and Group 3, 24 +/- 26 mm decrease. There was no statistically
      significant difference in pain relief between the three groups on univariate
      analysis or multivariable regression. In conclusion, the addition of Donnatal or
      Donnatal + lidocaine to an antacid did not relieve dyspepsia better than plain
      antacid. The "GI Cocktail" concoction may not be necessary.

PMID- 14585450
TI  - Rizatriptan RPD for severe migraine in the emergency department--a multicenter
      study.
AB  - Many patients with severe migraine come to the Emergency Department (ED) due to
      failure of different drug regimens to stop their headache. We treated 98 patients
      with severe migraine who were seen in three different EDs. We used rizatriptan
      RPD wafers 10 mg and observed the patients for 2 h. We found that at 2 h, 92.9%
      (91/98) of the patients had pain relief, and 73.5% were pain free. The mean time
      to pain relief was 26.9 +/- 29.6 min with a median of 15 min, and the time to
      pain free was 70.2 +/- 47.3 min with a median of 75 min. Eighty-five percent of
      the patients were free of associated symptoms, such as nausea and vomiting, at 2
      h with a mean time to symptom free of 55 +/- 47.5 min and a median of 45 min.
      Rizatriptan was reported to be much better than other drugs by 74.4% of the
      patients. Side effects were minor and transient. Recurrence of migraine occurred
      part of the day in 17.1% of the patients and all day or almost all day in 8.6% of
      the patients only. The results were consistent in all three EDs. We conclude that
      rizatriptan RPD is very effective and reliable as a first-line therapy for acute
      migraine in the ED. It dissolves immediately in the mouth without the
      inconvenience of an injection. It works fast and has few side effects and low
      headache recurrence.

PMID- 14585451
TI  - Effect of paramedic experience on orotracheal intubation success rates.
AB  - This study's objective was to determine the effect of paramedic experience on
      orotracheal intubation success in prehospital adult nontraumatic cardiac arrest
      patients. This retrospective study analyzed all attempted intubations of
      prehospital adult nontraumatic cardiac arrest patients between January 1, 1997
      and April 30, 1997 in an urban, all ALS service. Data were abstracted from EMS
      reports and intubation data forms. Variables included months of experience,
      number of patients in whom intubation was attempted, number of intubation
      attempts, success per attempt, and success per patient. Ninety-eight paramedics
      performed 909 intubations on 1066 cardiac arrest patients, yielding an intubation
      success rate of 85.3%. The median months of experience was 59.5 (Range 5-223).
      The median number of patients in whom intubation was attempted per paramedic was
      10 (Range 1-36). The mean intubation success rate per paramedic was 80.6% (+/-
      22.4, 95% CI 76.1, 85.1). There was significant correlation between total number
      of patients in whom intubation was attempted and intubation success rate (p
      <.001, R = 0.32). There was no correlation between months of experience and
      intubation success rate. In conclusion, the number of patients in whom intubation
      was attempted per paramedic was significantly correlated with the intubation
      success rate. Months of experience per paramedic had no significant correlation
      with intubation success rate.

PMID- 14585452
TI  - A seven-year experience in expedition medicine: the Juneau Icefield Research
      Program.
AB  - There have been relatively few attempts to document the optimal medical support
      for wilderness expeditions, and none of these previous reports includes physician
      level providers. Here we document our experience with physician-level medical
      support to an annual wilderness expedition in Alaska. This report utilizes data
      collected from 1994 to 2000 as part of the medical response to the Juneau
      Icefield Research Project, an annual research expedition to the Alaskan
      wilderness involving up to 60 students and professors. Medical supplies and
      equipment were catalogued, and 7 years of medical logs were reviewed with data
      presented in descriptive fashion. The majority of diseases encountered included
      gastrointestinal illness, minor orthopedic injuries, urinary tract infections,
      illness related to sun exposure, and kidney stones. Several patients required
      evacuation by helicopter to the nearest medical facility. The logistical
      challenges of medical treatment in this setting are discussed.

PMID- 14585453
TI  - Nonaneurysmal subarachnoid hemorrhage secondary to tuberculous meningitis: report
      of two cases.
AB  - Nontraumatic subarachnoid hemorrhage, one of the life-threatening diseases seen
      in Emergency Departments, is rarely caused by conditions other than rupture of
      saccular aneurysms. We report two cases of suspected tuberculous meningitis
      complicated with nonaneurysmal subarachnoid hemorrhage confirmed by conventional
      cerebral angiography. Tuberculous meningitis should be considered in the
      differential diagnoses in cases of nonaneurysmal subarachnoid hemorrhage,
      especially in tuberculosis endemic areas.

PMID- 14585454
TI  - Lymphocytic vasculitis associated with the anthrax vaccine: case report and
      review of anthrax vaccination.
AB  - Anthrax is caused by the spore-forming bacteria Bacillus anthracis. It occurs
      naturally, but recently has been manufactured as a biological warfare agent. This
      makes prophylaxis for anthrax an urgent concern and efforts are ongoing for the
      production of an efficient and safe vaccine. Side effects to the current anthrax
      vaccine are usually minor and mainly consist of local skin reactions.
      Occasionally an unusual complication may occur; a case of a patient with
      lymphocytic vasculitis temporally associated with the anthrax vaccine is
      reported.

PMID- 14585455
TI  - Sudden unexplained hemolysis occurring in an infant due to presumed Loxosceles
      envenomation.
AB  - We report the case of a 3-week-old infant referred for evaluation of sudden onset
      jaundice and unexplained hemolysis. After an exhaustive workup, the most likely
      etiology was found to be envenomation by a brown recluse spider, Loxosceles
      reclusa. This case underscores the fact that severe loxoscelism may occur in the
      absence of the classically described necrotic cutaneous lesion, and represents
      one of the youngest presumed cases of loxoscelism. We present the case to
      illustrate the importance of considering loxoscelism in the differential
      diagnosis of sudden massive hemolysis in children, particularly in endemic areas
      of the midwestern and southern United States.

PMID- 14585456
TI  - Effectiveness of octreotide in a case of refractory sulfonylurea-induced
      hypoglycemia.
AB  - The use of sulfonylurea medications in the treatment of type 2 diabetes mellitus
      is common. Patients who present to the Emergency Department after ingestion of
      excessive amounts of suflonylurea medications often have hypoglycemia refractory
      to dextrose administration. Standard care includes the administration of
      dextrose, glucagon, and diazoxide. Recently, the use of octreotide has been
      described as an alternative treatment in these patients. We present a case of a
      20-year-old woman who ingested 900 mg of glyburide causing refractory
      hypoglycemia resistant to treatment with intravenous dextrose, glucagon, and
      diazoxide. Octreotide administration rapidly reversed hypoglycemia allowing
      patient stabilization and eventual discharge without any significant adverse
      events.

PMID- 14585457
TI  - Artifactual elevation of lactate in ethylene glycol poisoning.
AB  - The diagnosis of ethylene glycol poisoning is based on nonspecific clinical
      symptoms and signs and indirect and direct laboratory measurement. Few
      institutions have timely access to direct measurement of ethylene glycol. As a
      result, diagnosis sometimes can be delayed and therapy initiated late. We present
      two cases of ethylene glycol poisoning. These cases demonstrate the need to
      recognize the false elevation of lactate in some chemistry analyzers due to the
      interference of glycolic acid, a metabolite of ethylene glycol. Using the
      "lactate gap" in comparing the measurement of lactate with two commonly used
      chemical analyzers aids in differentiating ethylene glycol poisoning from lactic
      acidosis.

PMID- 14585459
TI  - Are one or two dangerous? Clonidine and topical imidazolines exposure in
      toddlers.
AB  - Clonidine and the imidazolines, commonly found in topical ophthalmic and nasal
      decongestants, are chemically related drugs that have been responsible for many
      pediatric poisonings. These medications can cause significant morbidity in small
      doses. A review of the available literature reveals that young children have
      exhibited severe signs and symptoms after ingesting as little as one to two
      clonidine tablets or 2.5 ml of a topical imidazoline product. Central nervous
      system depression, respiratory depression, and cardiovascular instability are the
      most common features of poisoning. Signs and symptoms develop rapidly, within 4-6
      h. Care is supportive. Death is rare, but many poisoned patients require
      monitoring in an intensive care setting.

PMID- 14585461
TI  - Fever and rash.

PMID- 14585460
TI  - Electrocardiographic manifestations: ventricular tachycardia.
AB  - Ventricular tachycardia is a serious rhythm disturbance that originates from any
      part of the myocardium or conduction system below the atrioventricular node.
      Ventricular tachycardia (VT) presents with a wide QRS complex and a rate greater
      than 120 beats/min. Ventricular tachycardia is frequently encountered as a
      complication of coronary artery disease or cardiomyopathy; furthermore, VT is
      also seen in patients with medication adverse effect or electrolyte disturbance.
      Ventricular tachycardia presents electrocardiographically in several forms,
      including monomorphic and polymorphic VT. As is true in most Emergency Department
      presentations, the Emergency Physician must approach the dysrhythmic patient from
      an undifferentiated perspective, in this instance, the wide complex tachycardia
      (WCT) scenario. The electrocardiographic differential diagnosis of WCT
      classically includes VT and supraventricular tachycardia with aberrant intra
      ventricular conduction. This article will review the electrocardiographic
      presentations encountered in patients with ventricular tachycardia.

PMID- 14585462
TI  - Massive pneumocephalus after minimal head trauma.

PMID- 14585463
TI  - A case of typhoid fever associated with hemophagocytic syndrome.

PMID- 14585464
TI  - The efficacy of a safe, effective non-narcotic treatment of migraine headache.

PMID- 14585465
TI  - Systemic bioavailability of eye medications.

PMID- 14585466
TI  - Emergency medicine in South Africa: a personal perspective.
AB  - As efforts are made to make Emergency Medicine and the Journal of Emergency
      Medicine more international, the different systems of medical education and
      practice trends in other countries should be considered when making suggestions.
      This article is a personal perspective of a surgeon who has been involved in
      emergency care in both the United States and South Africa. The system in the
      United States can be defined as "mature." Although the system in South Africa has
      been defined as "underdeveloped," efforts are underway to establish Emergency
      Medicine as a separate, independent discipline. Some of the differences in
      medical education, postgraduate training, and disease prevalence are highlighted.
      A significant number of South Africans use the services of traditional healers,
      and a brief review of their services is included.

PMID- 14585467
TI  - Emergency Department patient perceptions of privacy and confidentiality.
AB  - The study objective was to determine if Emergency Department (ED) patients
      experience breaches of privacy and confidentiality during their ED stay and to
      determine if the type of room in which the patient is placed affects privacy. We
      surveyed a convenience sample of ED patients at the conclusion of their ED stay
      regarding their privacy and confidentiality. Overall, 36% of patients overheard
      conversations with similar frequencies in walled and curtained rooms. The
      location of conversations overheard varied depending on the type of patient room,
      as curtained rooms allowed conversations from adjacent rooms to be overheard and
      walled rooms allowed more conversations from the hallway or nursing station to be
      overheard. Patients felt more comfortable giving their history and having
      physical examinations performed in walled vs. curtained rooms. Inappropriate or
      unprofessional comments by staff were heard by 1.6% of patients. Health care
      providers in the ED need to be aware of breaches in confidentiality and privacy,
      as our patients deserve respect of their privacy and confidentiality during their
      ED visit.

PMID- 14585471
TI  - The sonocrystallisation of ice in sucrose solutions: primary and secondary
      nucleation.
AB  - Two investigations of the sonocrystallisation of ice are reported for solutions
      in the concentration range of 0-45 wt.% sucrose. The first, carried out at 20 kHz
      using a commercial sonicator shows clear evidence of the stimulation of primary
      nucleation, by increasing the temperature at which nucleation takes place. The
      nucleation temperature is also increased as the ultrasonic power output level or
      duty cycles are increased. The second uses a novel measurement cell which permits
      the direct visualisation of the crystallisation and cavitation with a light
      microscope while different levels of alternating pressures at a frequency of 67
      kHz are applied to the sample, whose heating and cooling is carefully controlled
      and monitored. This provides confirmation of the fragmentation of ice dendrites
      growing in a sucrose solution to produce smaller new ice crystals (secondary
      nucleation). These observations show that the primary and secondary nucleation of
      ice are both possible during the sonocrystallisation of ice.

PMID- 14585472
TI  - Ultrasonic scattering cross sections of shell-encapsulated gas bubbles immersed
      in a viscoelastic liquid: first and second harmonics.
AB  - The oscillations of gas bubbles, without shell, immersed in viscoelastic liquids
      and driven by an acoustic wave have been the subject of several investigations.
      They demonstrate that the viscosity coefficient and the spring constant of the
      liquid have significant influence on the scattering cross section of the gas
      bubble. For shell-encapsulated gas bubbles, the investigations have been
      concentrated to bubbles immersed in a pure viscous liquid. This present work
      computes the ultrasonic scattering cross section, first and second harmonics, of
      shell-encapsulated gas bubbles immersed in a viscoelastic liquid. The theoretical
      model of the bubble oscillation is based on the generalized Rayleigh-Plesset
      equation of motion of a spherical cavity immersed in a viscoelastic liquid
      represented by a three-parameter linear Oldroyd model. The scattering cross
      section is computed for Albunex type of bubble (shell thickness=15 nm, shell
      shear viscosity=1.77 Pas, shell modulus of rigidity=88.8 MPa) irradiated by a 3.5
      MHz ultrasonic pressure wave with an amplitude of 30 kPa. The results demonstrate
      that encapsulated bubbles respond independently of the surrounding liquid being
      pure viscous or viscoelastic as long as the surrounding liquid shear viscosity is
      as low as 10(-3) Pas. Nevertheless, for higher shear viscosities, the bubble
      responds differently if the surrounding liquid is pure viscous or viscoelastic.
      In general, the scattering cross sections of first and second harmonics are
      larger for the viscoelastic liquid.

PMID- 14585473
TI  - Estimation of ultrasonic attenuation in a bone using coded excitation.
AB  - This paper describes a novel approach to estimate broadband ultrasound
      attenuation (BUA) in a bone structure in human in vivo using coded excitation.
      BUA is an accepted indicator for assessment of osteoporosis. In the tested
      approach a coded acoustic signal is emitted and then the received echoes are
      compressed into brief, high amplitude pulses making use of matched filters and
      correlation receivers. In this way the acoustic peak pressure amplitude probing
      the tissue can be markedly decreased whereas the average transmitted intensity
      increases proportionally to the length of the code. This paper examines the
      properties of three different transmission schemes, based on Barker code, chirp
      and Golay code. The system designed is capable of generating 16 bits
      complementary Golay code (CGC), linear frequency modulated (LFM) chirp and 13-bit
      Barker code (BC) at 0.5 and 1 MHz center frequencies. Both in vivo data acquired
      from healthy heel bones and in vitro data obtained from human calcaneus were
      examined and the comparison between the results using coded excitation and two
      cycles sine burst is presented. It is shown that CGC system allows the effective
      range of frequencies employed in the measurement of broadband acoustic energy
      attenuation in the trabecular bone to be doubled in comparison to the standard
      0.5 MHz pulse transmission. The algorithm used to calculate the pairs of Golay
      sequences of the different length, which provide the temporal side-lobe
      cancellation is also presented. Current efforts are focused on adapting the
      system developed for operation in pulse-echo mode; this would allow examination
      and diagnosis of bones with limited access such as hip bone.

PMID- 14585474
TI  - Laser-ultrasonic generation of Lamb waves in the reaction force range.
AB  - The Laser-ultrasonic generation of Lamb waves in an elastic plate is investigated
      theoretically and experimentally for a laser source whose intensity is high
      enough to create reaction forces (normal tractions) on the illuminated surface of
      the specimen. The analytical solutions for transient waves are derived using the
      integral transform method first by considering an arbitrary source shape and time
      excitation function, and then specifically for circular and line source shapes.
      The simulation study allows us not only to predict the behavior of individual
      wave modes but also to construct the overall responses; thus it helps us better
      understand the wave excitation mechanisms. The dispersive and multi-modal nature
      of laser-generated Lamb waves is presented by showing the spatiotemporal Fourier
      transform of displacements obtained by the simulation study. The transform,
      displayed in the frequency-wave number domain, enunciates the characteristics of
      the propagating individual Lamb wave modes. The simulation results are then
      compared with the 2-D Fourier transform of a set of experimental data obtained by
      scanning an aluminum plate specimen.

PMID- 14585475
TI  - Hydrophones' effective diameter measurements as a quasi-continuous function of
      frequency.
AB  - The spatial averaging effect is strongly dependent on the active aperture of the
      hydrophone probes used to measure ultrasound fields. An experimental method was
      developed to determine the effective diameter of the probes as a quasi-continuous
      function of frequency. The implementation of the method utilizes the time delay
      spectrometry (TDS) technique and a set of focused acoustic sources. The use of
      focused sources ensured plane wave conditions for the whole frequency range and
      TDS eliminated all the reflections from the water tank boundaries. This approach
      allows effective diameter of circular aperture hydrophones to be determined as a
      quasi-continuous function of frequency up to 40 MHz. The measurements were
      performed for both needles and membrane designs having nominal diameters ranging
      from 50 to 500 microm. The results were successfully employed in the development
      of spatial averaging correction algorithms. Current efforts are being focused on
      extension of the frequency range up to 60 MHz by using a novel measurement
      technique termed time gating frequency analysis.

PMID- 14585476
TI  - Hysteresis in response of nonlinear bistable interface to continuously varying
      acoustic loading.
AB  - In many experimental situations it is an equation of the forced relaxator and not
      of the forced oscillator that describes a variation in the acoustic field of the
      interface width (i.e. of a characteristic distance between the surfaces composing
      the interface). The developed theory predicts that some types of the nonlinear
      relaxators (depending on the structure of the nonlinear interaction force between
      the surfaces) exhibit hysteresis in their response to continuous acoustic loading
      of first increasing and then decreasing amplitude. Nonlinear (unharmonic)
      variation of the interface width starts at threshold amplitude of the incident
      sinusoidal acoustic wave, which is higher than threshold amplitude for returning
      to sinusoidal motion. This dynamic hysteresis (and accompanying it bistability)
      are possible, in particular, if the dependence of the effective interaction force
      on the interface width admits two quasi-equilibrium positions of the interface
      (bistable interface) or if the force itself is hysteretic (hysteretic interface).
      These theoretical predictions are relevant to some recent experimental
      observations on the interaction of powerful ultrasonic fields with cracks.

PMID- 14585477
TI  - Resonant acoustic scattering by a finite linear grating of elastic shells.
AB  - Theoretical and experimental studies of the acoustic scattering by a finite
      linear grating of elastic cylindrical shells are performed. It is observed that a
      resonant interaction takes place at low frequency when the shells are very close
      to each other. This phenomenon can be clearly associated to the Scholte-Stoneley
      wave that propagates around a single shell. It is shown that each resonance of
      the Scholte-Stoneley wave is split up into N resonances when N shells compose the
      grating.

PMID- 14585478
TI  - Computer generated optical holographic fringe patterns for the analysis of
      vibrating structures.
AB  - Optical holographic interference fringe patterns on rods and bars vibrating in
      ultrasonic resonance (standing waves) are predicted by computer simulations. The
      simulations are based on a combination of finite element calculations with
      calculations based on the theory of holographic interference fringe generation.
      The hypothetical fringe patterns are then compared to holographic fringe images
      obtained by the experiment (time average holograms). The holographic arrangement
      and the mechanical part of the ultrasonic system (transducer, horn and specimen)
      were fixed on a commercial rigid optical table supported on air bags to isolate
      it from ground vibrations. Thus it is shown that the scope of the study can be
      reached with a minimum of experimental effort, i.e., with basic laser optical
      equipment. It is shown that provided the system operates in the desired mode,
      good agreement between the theoretical and the real image is given. Finally
      examples of the possible influence of defects or of parasitic modes of vibration
      on the appearance of the fringe patterns are given.

PMID- 14585479
TI  - KLM model for lossy piezoelectric transducers.
AB  - A KLM model has been developed using equivalent circuits to analyze the effects
      of different loss mechanisms on the transducer performance in the time and
      frequency domain. Transducers from two different piezoelectric materials (lead
      zirconate-titanate (PZT) and polyvinylidene fluoride) were constructed to
      validate our model. Experimental results are in good agreement with the
      theoretical simulation.

PMID- 14585480
TI  - Inter-society standards for the performance of brachytherapy: a joint report from
      ABS, ACMP and ACRO.
AB  - PURPOSE: The proliferation of various brachytherapy modalities for different
      anatomical sites necessitates the creation of standards for brachytherapy.
      METHODS: A panel consisting of members of The American Brachytherapy Society
      (ABS), The American College of Medical Physics (ACMP) and The American College of
      Radiation Oncology (ACRO) developed standards for the clinical practice and
      quality assurance (QA) of brachytherapy. These were based upon their clinical
      experience and a review of the literature. RESULTS: Recommended practice
      standards are presented for clinical processes, treatment planning, equipment,
      facilities, QA, dose evaluation, dose specification, dose reporting, the
      training, and credentialing of personnel, and radiation
      control/safety/protection. Safe and efficacious performance of brachytherapy
      requires a highly structured QA program and carefully designed treatment delivery
      processes, as well as a coordinated effort amongst the team members. CONCLUSION:
      Standards for clinical brachytherapy are proposed. Practitioners are encouraged
      to use these standards to design and implement a consistent and efficacious
      brachytherapy program.

PMID- 14585481
TI  - The DNA synthesome: its potential as a novel in vitro model system for studying S
      phase specific anticancer agents.
AB  - A considerable effort is being made to discover more effective anticancer agents
      and to develop rapid, accurate, and reliable methods for evaluating the
      usefulness of the new compounds and analyzing their mechanisms of action. In this
      regard, our laboratory was the first to report the isolation, characterization,
      and extensive purification of an intact, stable, and fully functional mammalian
      cell multiprotein complex, which we designated the DNA synthesome. The DNA
      synthesome has been isolated from a wide variety of mammalian cells as well as
      from tissues and has been shown to be fully competent to support SV40 origin
      specific and large T antigen-dependent DNA replication in vitro. In this article
      we will review the utilization of the DNA synthesome as a powerful in vitro model
      system for analyzing the mechanism of action of S-phase specific anticancer
      agents.

PMID- 14585482
TI  - Umbilical cord blood transplantation: current practice and future innovations.
AB  - As a source of hematopoietic stem cells (HSCs), umbilical cord blood (UCB) has
      the advantages of speed of availability, tolerance of 1-2 antigen HLA mismatch,
      and a low incidence of severe GVHD. Thus, UCB represents a highly convenient HSC
      source that may significantly extend the HSC donor pool. UCB transplantation
      (UCBT) has become a standard practice in the treatment of pediatric malignancies.
      Now, UCBT is being investigated in adults using both conventional and non
      myeloablative preparative regimens. As graft cell dose is the major factor
      determining hematopoietic recovery and survival in URD UCBT, methods to increase
      cell dose such as multiple-unit transplant and ex vivo expansion are being
      pursued. This review outlines the current status of UCBT with emphasis on current
      and future innovations.

PMID- 14585483
TI  - The pipeline of new anticancer agents for breast cancer treatment in 2003.
AB  - In recent years, strategy in cancer therapy in general, and breast cancer in
      particular, has been the use of maximum tolerated doses of toxic non-specific
      agents as well as the investigation of a range of new agents that specifically
      target tumor-related molecules, in a variety of biological pathways. The trial of
      chemotherapy (CT) versus chemotherapy+trastuzumab (Herceptin) in HER-2
      overexpressing metastatic breast cancer (MBC) was one of the first to use a
      biological agent in combination with chemotherapy with success and, together with
      some trials of taxanes in anthracycline-resistance patients one of the few to
      demonstrate an overall survival (OS) advantage in MBC. Five main molecular
      pathways are of particular interest in terms of new drug development in breast
      cancer: the estrogen receptor (ER) pathway, the tyrosine kinase signal
      transduction pathway, the cell cycle regulation pathway, the apoptosis pathway
      and the angiogenesis pathway. This review will focus on new agents, cytotoxic,
      hormonal and molecular-targeted, which are in advanced clinical stages of
      development for the treatment of MBC.

PMID- 14585484
TI  - Venous thromboembolism and cancer: new issues for an old topic.
AB  - Thromboembolic complications represent the second leading cause of death for
      cancer patients. Even though the correlation between cancer and a hypercoagulable
      state has been widely recognised, the pathogenesis of thromboembolism during
      malignancy is not yet entirely understood. The direct or indirect activation of
      the coagulation cascade favours neoplastic dissemination and metastasis.
      Disordered coagulation is encountered in up to 90% of cancer patients, although
      only 15% of them develop a localised acute or chronic deep venous thrombosis or a
      disseminated intravascular coagulation. This risk is significantly increased by
      chemotherapy, hormone therapy, surgery and central venous catheters. Therefore,
      much effort is needed to develop efficient prophylaxis and treatment, to reduce
      recurrence and bleeding and finally, to improve quality of life. Better knowledge
      about the biochemical bases of the coagulation process represents a pivotal step
      in cancer biology comprehension and global therapeutic management.

PMID- 14585485
TI  - Gemcitabine: current role and future options in the treatment of ovarian cancer.
AB  - Epithelial ovarian cancer is the gynecological malignancy with the highest
      mortality. The standard therapeutic approach for patients with advanced-stage
      epithelial ovarian cancer has been cytoreductive surgery followed by combination
      chemotherapy. Despite improvements in outcome via carboplatin/paclitaxel based
      chemotherapy, 30% of patients with ovarian cancer fail to respond to primary
      therapy; moreover, 55-75% of responders relapse within 1 or 2 years from the end
      of primary treatment and die of the disease within 5 years from their initial
      diagnosis. Gemcitabine has been shown to be active as a single agent and in
      combination with other drugs, including carboplatin and paclitaxel, in the
      treatment of patients with recurrent ovarian cancer. It is currently under
      evaluation in new combinations for initial therapy in ovarian cancer patients.

PMID- 14585486
TI  - Follow-up care of breast cancer survivors.
AB  - Breast cancer is the most common malignancy in women, affecting thousands of
      people each year. The majority of women are diagnosed with early stage breast
      cancer, which is curable. The follow-up care of the breast cancer survivor
      requires an understanding of the goals of follow-up and the short and long term
      side effects of breast cancer treatment. In this article, we will discuss the
      principles of follow-up care of the breast cancer survivor.

PMID- 14585487
TI  - Heart rate response is longer after negative emotions than after positive
      emotions.
AB  - Summary. Recent ambulatory findings showing comparable cardiovascular effects of
      positive and negative emotions are not consistent with the assumed etiological
      role of negative affect in stress-related diseases. We tested the hypothesis that
      regardless of initial reactivity, responses associated with negative emotions
      would be prolonged compared to responses associated with positive emotions.
      During 8 h, 33 healthy subjects from a general population reported their
      emotional arousal, emotional valence and physical activity and recorded their
      heart rates (HR) after a beep at each 60th min ('initial HR'; T0), followed by
      two 'prolonged activation' recordings, respectively 5 min later (T1) and 10 min
      later (T2). While emotional arousal and activity predicted initial HR, prolonged
      activation at T1 was solely predicted by emotional valence (negative affect) at
      T0, independent of emotional recovery. The results lend support to the hypothesis
      that cardiovascular activation after negative emotions last longer than after
      positive emotions. This finding is consistent with the view that prolonged
      activation, and not so much reactivity, might be a mechanism underlying the
      etiological role of negative emotions ('stress') in somatic disease.
      Perseverative cognition (worry, rumination) might be responsible for this
      prolonged activation.

PMID- 14585488
TI  - Analysis of frequency components of cortical potentials evoked by progressive
      misalignment of Kanizsa squares.
AB  - Cortical gamma oscillations (20-100 Hz) are thought to play an important role in
      encoding visual perception. If so they should emerge at about threshold. In the
      present investigation we examined the latter proposal. Visual responses were
      recorded in occipital, temporal and parietal areas (stimulus duration 512 ms).
      Oscillation strength and frequency were derived from FFT analysis and wavelet
      transforms. The specific goals of the present study are: 1: To examine the
      parallel between gamma oscillations and the psychometric threshold of perception
      of Kanizsa square (KS). The latter is gradually altered by a progressive
      misalignment of lower inducers (pacmen). Results show that the perception of the
      KS is altered by lateral displacements of the lower inducers as small as 0.1 to
      0.2 degrees. In parallel, high frequency components of cortical responses gain in
      strength with misalignments. 2: Gamma oscillations emerge at or about the
      psychometric threshold. In addition, our data analysis demonstrates that gamma
      oscillations appear in short bursts (approx. 50 ms) in the time window between
      200 and 500 ms after stimulus onset. Furthermore, controls indicated that these
      oscillations are of the induced-gamma type. Thus, our experiments suggest that
      gamma oscillations are associated with image structures and may be induced by
      local properties of the target.

PMID- 14585489
TI  - Trait anxiety impact on the EEG theta band power changes during appraisal of
      threatening and pleasant visual stimuli.
AB  - The main objective of the present investigation was to examine whether trait
      anxiety construct would influence EEG event-related synchronization (ERS) of the
      theta power during viewing of visual threatening stimuli. The 62-channel EEG was
      recorded while low (LA, n= 18) and high (HA, n= 18) trait-anxious subjects viewed
      sequentially presented neutral, threatening and pleasant pictures. Between-group
      differences, related to stimulus emotionality, were linked to the test period of
      0-1000 ms after stimulus onset. In the low theta (4-6 Hz) at prefrontal sites HA
      exhibited deficient ERS in response to both threatening and pleasant stimuli in
      the right hemisphere, whereas LA yielded larger right than left hemisphere ERS in
      response to all the three stimulus categories. In the upper theta (6-8 Hz) group
      differences were associated with posterior cortical regions: HA exhibited the
      largest ERS to threatening and the lowest to pleasant stimuli, whereas LA
      prompted the largest ERS to pleasant and the lowest to neutral pictures. It is
      suggested that low theta right prefrontal hypoactivation favoring left
      hemispheric (i.e. more analytical) activity along with higher upper theta ERS of
      posterior cortical regions (i.e. enhanced higher order visual processing) to
      threatening stimuli could form the basis for neuropsychologically observed
      general bias towards threatening information in HA.

PMID- 14585490
TI  - Effect of 38 h of total sleep deprivation on the waking EEG in women: sex
      differences.
AB  - 38 h of sleep deprivation in women resulted in decreased alpha, increased theta
      and increased intrahemispheric correlation during rest and increased theta and
      reaction time during task. F3-O1 coherent activity was selectively decreased
      consistent with the role of sleep for recovery of frontal functions. Sleep
      deprivation effects were milder in women than in men, however, recovery was not
      complete suggesting that women need more sleep than men to recover.

PMID- 14585491
TI  - Hemodynamic responses to fear and disgust-inducing pictures: an fMRI study.
AB  - The majority of neuroimaging studies on affective processing have indicated that
      there are specific brain structures, which are selectively responsive to fear and
      disgust. Whereas the amygdala is assumed to be fear-related, the insular cortex
      is most likely involved in disgust processing. Since these findings are mainly a
      result of studies focusing exclusively either on fear, or on disgust, but rarely
      on both emotions together, the present experiment explored the neural effects of
      viewing disgusting and fear-inducing pictures in contrast to neutral pictures.
      This was done by means of functional magnetic resonance imaging (fMRI) with 19
      subjects (nine males, ten females), who also gave affective ratings for the
      presented pictures. The fear and the disgust pictures were able to induce the
      target emotions and they received comparable valence and arousal ratings. The
      processing of both aversive picture types was associated with an increased brain
      activation in the occipital-temporal lobe, in the prefrontal cortex, and in the
      thalamus. The amygdala was significantly activated by disgusting, but not by fear
      inducing, pictures. Thus, our data are in contrast with the idea of highly
      emotion-specific brain structures and rather suggest the existence of a common
      affective circuit.

PMID- 14585492
TI  - Two- and three-dimensional mental rotation tasks lead to different parietal
      laterality for men and women.
AB  - Thirty-two college students (16 male, 16 female) had EEG recorded during
      computerized two- and three-dimensional mental rotation tasks. The simple two
      dimensional mental rotation task was associated with more left parietal than
      right parietal activation in men and more right parietal than left parietal
      activation in women. The complex three-dimensional mental rotation task was
      associated with greater right parietal than left parietal activation in both men
      and women. Men performed better than women on the three-dimensional task and
      there were no differences between men and women on the two-dimensional task. It
      was concluded that men and women may be using different neurological strategies
      on two- and three-dimensional mental rotation tasks.

PMID- 14585493
TI  - Lie detection with contingent negative variation.
AB  - topographies of contingent negative variation (CNV) were recorded in a paradigm
      of delayed response with feedback for three kinds of faces: familiar, strange and
      target. Subjects made responses to the faces according to whether the faces were
      familiar or not, but also, gave deliberately deceptive responses to target faces
      to 'cheat the computer'. Subjects were told that the computer could judge whether
      they were being honest or not. For each trial of the experiment, if subjects
      cheated the computer successfully and their responses were judged as honest and
      they were given a reward, otherwise they received a penalty. In this simulated
      lie detection test, CNV exhibited more negative shifts for target than those for
      non-target (familiar and strange). These differences could be accounted for by
      subjects' motivation and uncertainty about passing the test. With the results of
      further paired t-tests between target and non-target faces at each electrode, CNV
      was demonstrated as a reliable indicator for lie detection. In addition, vector
      length was used to capture global CNV information and was found to be a very good
      indicator, even better than the CNV information at the individual electrode
      sites.

PMID- 14585494
TI  - Alternative ways to think about mRNA sequences and proteins that appear to
      promote internal initiation of translation.
AB  - Translation of some mRNAs is postulated to occur via an internal initiation
      mechanism which is said to be augmented by a variety of RNA-binding proteins. A
      pervasive problem is that the RNA sequences to which the proteins bind were not
      rigorously proven to function as internal ribosome entry sites (IRESs). Critical
      examination of the evidence reveals flaws that leave room for alternative
      interpretations, such as the possibility that IRES elements might function as
      cryptic promoters, splice sites, or sequences that modulate cleavage by RNases.
      The growing emphasis on IRES-binding proteins diverts attention from these
      fundamental unresolved issues. Many of the putative IRES-binding proteins are
      heterogeneous nuclear ribonucleoproteins that have recognized roles in RNA
      processing or stability and no recognized role in translation. Thus the mechanism
      whereby they promote internal initiation, if indeed they do, is not obvious. Some
      recent experiments were said to support the idea that IRES-binding proteins cause
      functionally important changes in folding of the RNA, but the evidence is not
      convincing when examined closely. The proteins that bind to some (not all) viral
      IRES elements include a subset of authentic initiation factors. This has not been
      demonstrated with any candidate IRES of cellular origin, however; and even with
      viral RNAs, the required chase experiment has not been done to prove that a pre
      bound initiation factor actually mediates subsequent entry of ribosomes. In
      short, the focus on IRES-binding proteins has gotten us no closer to
      understanding the mechanism of internal initiation. Given the aforementioned
      uncertainty about whether other mechanisms (splicing, cryptic promoters) might
      underlie what-appears-to-be internal initiation, a temporary solution might be to
      redefine IRES to mean "internal regulatory expression sequence." This compromise
      would allow the sequences to be used for gene expression studies, for which they
      sometimes work, without asserting more than has been proven about the mechanism.

PMID- 14585495
TI  - Molecular cloning and characterization of Atp6v1b1, the murine vacuolar H+ 
      ATPase B1-subunit.
AB  - The multisubunit vacuolar-type proton-translocating ATPases (H(+)-ATPases)
      mediate the acidification of various intracellular organelles. In a subset of
      tissues, they also mediate H(+) secretion at the plasma membrane. Two isoforms of
      the H(+)-ATPase B-subunit exist in humans; we have shown that mutations in
      ATP6V1B1, encoding the B1-isoform, cause the clinical condition distal renal
      tubular acidosis. Here we report the cloning and characterization of murine
      Atp6v1b1, which encodes a 513-amino acid (aa) protein with 93% identity to human
      ATP6V1B1. Genomic organization is conserved between the murine and human H(+)
      ATPase B1-subunits, and Atp6v1b1 maps to a region of mouse chromosome 6 syntenic
      to human 2p13, the location of ATP6V1B1. Northern blotting detects a 2.2-kb
      Atp6v1b1 transcript in the kidney and testis, but not other major organs. In
      mouse kidney, the B1-subunit localizes to intercalated cells of the cortical and
      medullary collecting duct. B1 protein levels were not increased in either mouse
      renal cortex or medulla after either 2 or 7 days of oral acid loading. These
      results demonstrate that Atp6v1b1 encodes the murine ortholog of human ATP6V1B1
      and provides a tool for future development of animal models based on manipulation
      of the Atp6v1b1 genomic locus.

PMID- 14585497
TI  - Characterization of AOC2 gene encoding a copper-binding amine oxidase expressed
      specifically in retina.
AB  - We have previously cloned a human, retina-specific, amine oxidase gene (RAO, gene
      symbol: AOC2), a member of the copper-binding amine oxidase super family. AOC2
      shares sequence identity with the human kidney amine oxidase gene (KAO, gene
      symbol: AOC1) and the vascular adhesion protein-1 gene (VAP-1, gene symbol:
      AOC3). For further analysis of AOC2, the sequences surrounding the human AOC2 and
      the complete mouse and partial rat homologue of AOC2 were cloned for
      characterization. Real-time quantitative PCR, in situ hybridization, and
      immunohistochemistry were performed to determine the specific expression of AOC2
      in the mouse retina and especially in the retinal ganglion cells. Our results
      demonstrated that the copper-binding motif and the enzyme active site of AOC1 and
      AOC3 were both conserved in mouse AOC2. The human and mouse AOC2 was flanked by
      two genes, the Psme3 gene for PA-28 gamma subunit and, surprisingly, the AOC3
      gene. Rat AOC2 contained a stop codon that terminated the peptide length to 127
      amino acids. The presence of human and rat AOC pseudogene in this region, in
      addition to the tandemly positioned two AOC genes, indicates the possibility of
      successful AOC3 replication to retina-specific AOC2 for human and mouse but
      unsuccessful for rat.

PMID- 14585496
TI  - EID-2, a novel member of the EID family of p300-binding proteins inhibits
      transactivation by MyoD.
AB  - Skeletal muscle differentiation has been shown to be dependent on the expression
      of Rb and p300. We recently cloned a novel inhibitor of muscle differentiation
      called EID-1, which interacted with both of these factors. In a database search
      for related molecules, we have cloned and characterized a new EID-1 family
      member, EID-2. This 28-kDa protein encodes a 236-amino-acid protein with
      significant similarity to EID-1 in its C-terminus. EID-2 displays developmentally
      regulated expression with high levels in adult heart and brain. Overexpression of
      EID-2 inhibits muscle-specific gene expression through inhibition of MyoD
      dependent transcription. This inhibitory effect on gene expression can be
      explained by EID-2's ability to associate with and inhibit the acetyltransferase
      activity of p300. These data suggest that EID-1 and -2 represent a novel family
      of proteins that negatively regulate differentiation through a p300-dependent
      mechanism.

PMID- 14585498
TI  - Characterization of PTM5 in aspen trees: a MADS-box gene expressed during woody
      vascular development.
AB  - The vascular component of trees possesses some of the most specialized processes
      active in the formation of roots, stems, and branches, and its wood component
      continues to be of primary importance to our daily lives. The molecular
      mechanisms of wood development, however, remain poorly understood with few well
      characterized regulatory genes. We have identified a vascular tissue-specific
      MADS-box gene, Populus tremuloides MADS-box 5 (PTM5) that is expressed in
      differentiating primary and secondary xylem and phloem. Phylogenetic analysis has
      shown that PTM5 is a member of the SOC1/TM3 class of MADS-box genes. Temporal
      expression analysis of PTM5 in staged vascular cambium and other tissues
      indicated that PTM5 expression is seasonal and is limited to spring wood
      formation and rapidly expanding floral catkins. Spatial expression analysis using
      in situ hybridization revealed that PTM5 expression is localized within a few
      layers of differentiating vascular cambium and xylem tissues as well as the
      vascular bundles of expanding catkins. Since many MADS-box genes are known to act
      as transcription factors, these results suggest that the coordinated expression
      of PTM5 with other vascular developmental genes may be a hallmark of the complex
      events that lead to the formation of the woody plant body.

PMID- 14585499
TI  - Isolation and characterization of the first non-autonomous transposable element
      in amphioxus, ATE-1.
AB  - We report the first class II transposon in cephalochordates, which we have named
      Amphioxus Transposable Element 1 (ATE-1). ATE-1 members have been identified in
      the genome of Branchiostoma lanceolatum (BlATE-1) and B. floridae (BfATE-1).
      Structural analysis revealed that ATE-1 elements consist of a central region (CR)
      with no homology with any coding sequence, nor any detectable open reading frame
      (ORF), flanked by internal direct repeats (DR) of about 100 nt, each adjacent to
      a terminal inverted repeat (TIR) of 16 nt. Although the estimated copy number in
      the amphioxus genome is low, there is evidence of mobility. Sequence and
      hybridization analyses pointed to TIR and DR inter-species conservation, whereas
      no structural similarities among the CR were detected. Moreover, this element is
      found in two amphioxus species that diverged long ago, which argues in favor of
      its ancient origin. However, the structural hallmarks needed for transposition
      are still preserved.

PMID- 14585500
TI  - Differential expression of PE and PE_PGRS genes in Mycobacterium tuberculosis
      strains.
AB  - In this study, the expression of the Mycobacterium tuberculosis PE,
      PE_polimorphic GC-rich sequences (PGRS) gene family encoding approximately 99
      glycine-rich proteins was assayed by reverse-transcriptase polymerase chain
      reaction (RT-PCR) in M. tuberculosis H37Rv, Mycobacterium canettii and two
      clinical isolates of M. tuberculosis. Restriction analyses and sequencing of the
      RT-PCR products showed that all the strains expressed the PE Rv1172c gene while
      the PE_PGRS Rv3652 gene was only expressed by one of the M. tuberculosis clinical
      isolates, and the PE_PGRS Rv0578c was not expressed by M. canettii. It was also
      determined that the PE_PGRS Rv0278c and Rv0279c were not expressed by any of the
      studied strains. The data presented in this report show that the PE, PE_PGRS
      genes are differentially expressed in M. tuberculosis strains during in vitro
      growth. These findings suggest that PE, PE_PGRS genes may play a role in protein
      variation between M. tuberculosis strains.

PMID- 14585501
TI  - Influence of metal ions on gene expression of BALB 3T3 fibroblasts.
AB  - It is widely recognized that metal compounds may modify gene expression. In this
      context, we have searched for genes whose expression may be affected by cadmium
      and platinum ions within the context of a cell culture system. Cadmium is well
      known for its carcinogenic potential while platinum is destined to become more
      and more interesting because of its increasing use in the automotive industries.
      By applying differential display to cultures of mouse fibroblast, we have
      identified two transcripts (acute lymphoblastic leukemia-1, All-1, and a novel
      gene named metal-responsive gene, MERE-1) that were responsive to platinum and
      cadmium ions. Moreover, further experiments with a panel of metal compounds have
      shown that MERE-1 was strongly induced also by La(NO3)2 and Cr(NO3)3, and to a
      lesser extent, by Na2CrO4 and (NH4)2TeCl6.

PMID- 14585502
TI  - An adult-specific CYP6 P450 gene is overexpressed in a pyrethroid-resistant
      strain of the malaria vector, Anopheles gambiae.
AB  - Many malaria control programmes are based on insecticide application as
      adulticides, often in the form of pyrethroid-impregnated bed nets. However, the
      efficacy of this control measure can be reduced by genetic changes in vector
      insecticide susceptibility. Pyrethroid resistance has been detected in the major
      African malaria vector, Anopheles gambiae, and has been attributed to a
      combination of target site insensitivity and increased oxidative metabolism of
      the insecticide, catalysed by cytochrome P450s. An adult-specific cytochrome P450
      monooxygenase 6 (CYP6) P450 gene, CYP6Z1, located within a large cluster of
      cytochrome P450 genes in chromosome arm 3R of An. gambiae, is expressed
      approximately 11-fold higher in males and 4.5-fold in females from a pyrethroid
      resistant strain than in a susceptible strain from the same geographical area. In
      both strains, CYP6Z1 expression is higher in males than females. Southern blot
      analysis discounted gene amplification as a cause of this overexpression. The
      isolation of An. gambiae cDNAs encoding cytochrome b(5) and nicotinamide adenine
      dinucleotide phosphate (reduced form) (NADPH)-cytochrome P450 reductase cDNAs is
      also reported.

PMID- 14585503
TI  - GmPAP3, a novel purple acid phosphatase-like gene in soybean induced by NaCl
      stress but not phosphorus deficiency.
AB  - Purple acid phosphatases (PAPs) are commonly found in plants, but the
      physiological functions of different classes of PAPs are not thoroughly
      understood. In the present study, we identified a novel gene, GmPAP3, from salt
      stressed soybean using suppression subtractive hybridization (SSH) techniques.
      Protein sequence alignment studies and phylogenetic analysis strongly suggested
      that GmPAP3 belongs to the group of plant PAPs and PAP-like proteins that are
      distinct from those of fungi and animals. In addition, the invariable consensus
      metal binding residues of PAPs were all conserved in GmPAP3. Surprisingly,
      analysis of protein sorting signals showed that a putative mitochondrion
      targeting transit peptide is present on GmPAP3. Northern blot analysis revealed
      that NaCl stress causes a general induction of GmPAP3 expression in both roots
      and leaves of various cultivated (Glycine max) and wild (Glycine soja) soybean
      varieties. Further test using two genetically unrelated cultivated soybean
      varieties showed that the expression pattern of GmPAP3 is distinct from other PAP
      genes in soybeans. NaCl stress and oxidative stress but not phosphorus (P)
      starvation induces the expression of GmPAP3. These results suggest that the
      physiological role of GmPAP3 might be related to the adaptation of soybean to
      NaCl stress, possibly through its involvement in reactive oxygen species (ROS)
      forming and/or scavenging or stress-responding signal transduction pathways.

PMID- 14585505
TI  - Identification and characterization of ameloblastin gene in an amphibian, Xenopus
      laevis.
AB  - Ameloblastin (AMBN) is an enamel sheath protein that presumably has a role in
      determining the prismatic structure of growing enamel crystals. To investigate
      the relationship between the molecular evolution of the AMBN gene and development
      of enamel prismatic structures, it is considered to be of great significance in
      the identification of homologues of the AMBN genes in nonmammals whose teeth lack
      an enamel prismatic structure. Several clones containing AMBN cDNA were isolated
      from an African clawed toad tooth cDNA library by screening with a polymerase
      chain reaction (PCR) method. Sequence analysis of the clones revealed that they
      were derived from different genes (toad-A and toad-B), which were found to
      contain ORFs encoding 408- and 352-amino-acid proteins, respectively. The N
      terminal part of the toad AMBN proteins and the phosphorylation motif for casein
      kinase II, as well as several features, were found to be highly conserved
      throughout the evolution of tetrapods. Exon-intron boundaries were shared by toad
      and caiman genes with the exception of exons 6, 7 and 10 while human and caiman
      genes shared them exclusive of exons 8 and 9 which have been found only in the
      human. As for exon 7, it was absent in both toad genes. Moreover, the AMBN genes
      were transcribed only in the upper jaw, presumably in teeth. These results may
      provide useful information for investigation of the evolution of enamel.

PMID- 14585504
TI  - Egr-1 upregulates the Alzheimer's disease presenilin-2 gene in neuronal cells.
AB  - Regulation of the Alzheimer's disease (AD)-related gene, presenilin-2 (PSEN2),
      was analyzed in neuronal (SK-N-SH) and non-neuronal (human embryonic kidney 293,
      HEK293) cells. We show that the PSEN2 regulatory region includes two separate
      promoter elements, each located upstream of multiple transcription start sites in
      the first and second exons. The stronger upstream promoter, P1, has housekeeping
      characteristics: it resides in a CpG island, is TATA-less, and up to 83% of PSEN2
      P1 activity depends on a stimulating protein 1 (Sp1) site at the most 5'
      initiation site. However, the downstream promoter P2 includes neuronal-specific
      elements and two sites for early growth response gene-1 (Egr-1), a transcription
      factor upregulated in learning paradigms and implicated in neuronal plasticity,
      in response to injury. We show that Egr-1 binds to PSEN-P2, and that PSEN-P2
      activity is increased threefold by overexpression of Egr-1, and by 12-O
      tetradecanoylphorbol-13-acetate (TPA), which induces physiological Egr-1 levels.
      Egr-1 represses PSEN2-P1 activity by 50% in neuronal cells, suggesting it
      partially shifts promoter usage from PSEN2-P1 to PSEN2-P2. This could lead to a
      relative increase in shorter exon 2 transcripts, which may be more efficiently
      translated than exon 1 transcripts. Identification of PSEN2 as an Egr-1 target
      suggests a link between PSEN2 expression and Egr-1-related processes, which may
      impact on understanding PSEN-2's physiological function and its role in
      Alzheimer's disease.

PMID- 14585506
TI  - Mouse models of Down syndrome: how useful can they be? Comparison of the gene
      content of human chromosome 21 with orthologous mouse genomic regions.
AB  - With an incidence of approximately 1 in 700 live births, Down syndrome (DS)
      remains the most common genetic cause of mental retardation. The phenotype is
      assumed to be due to overexpression of some number of the >300 genes encoded by
      human chromosome 21. Mouse models, in particular the chromosome 16 segmental
      trisomies, Ts65Dn and Ts1Cje, are indispensable for DS-related studies of gene
      phenotype correlations. Here we compare the updated gene content of the finished
      sequence of human chromosome 21 (364 genes and putative genes) with the gene
      content of the homologous mouse genomic regions (291 genes and putative genes)
      obtained from annotation of the public sector C57Bl/6 draft sequence. Annotated
      genes fall into one of three classes. First, there are 170 highly conserved,
      human/mouse orthologues. Second, there are 83 minimally conserved, possible
      orthologues. Included among the conserved and minimally conserved genes are 31
      antisense transcripts. Third, there are species-specific genes: 111 spliced human
      transcripts show no orthologues in the syntenic mouse regions although 13 have
      homologous sequences elsewhere in the mouse genomic sequence, and 38 spliced
      mouse transcripts show no identifiable human orthologues. While these species
      specific genes are largely based solely on spliced EST data, a majority can be
      verified in RNA expression experiments. In addition, preliminary data suggest
      that many human-specific transcripts may represent a novel class of primate
      specific genes. Lastly, updated functional annotation of orthologous genes
      indicates genes encoding components of several cellular pathways are dispersed
      throughout the orthologous mouse chromosomal regions and are not completely
      represented in the Down syndrome segmental mouse models. Together, these data
      point out the potential for existing mouse models to produce extraneous
      phenotypes and to fail to produce DS-relevant phenotypes.

PMID- 14585507
TI  - The human gene CXorf17 encodes a member of a novel family of putative
      transmembrane proteins: cDNA cloning and characterization of CXorf17 and its
      mouse ortholog orf34.
AB  - We report the identification and cloning of a novel human gene, CXorf17, together
      with its mouse ortholog, orf34. The human and mouse transcripts were cloned from
      brain cDNA and encode deduced proteins of 1096 and 1091 amino acids,
      respectively. These proteins are 92% identical and 95% similar at the protein
      level. CXorf17 appears to be expressed at low levels and could be detected by RT
      PCR in several adult and fetal human tissues. Analysis of the deduced amino acid
      sequence identified five putative transmembrane domains but no significant
      homology to previously described protein domains or sequence motifs. The CXorf17
      protein has homology to two other non-annotated human proteins, C9orf10 and
      BC012177, the sequence similarity between them being strongest across two
      discrete domains of 250-270 amino acids in the N- and C-terminal parts of their
      sequences. We propose that these proteins belong to a previously undescribed
      family of putative transmembrane proteins. The identification of ESTs coding for
      similar proteins in other chordates but not lower eukaryotes suggests that these
      proteins may have first evolved during early chordate evolution. CXorf17 consists
      of 16 coding exons and maps to Xp11.22, approximately 14 kb telomeric to PRKWNK3
      and 27 kb centromeric to KIAA1111. Its identification contributes to the
      annotation of expressed genes in the proximal part of the X chromosome.

PMID- 14585508
TI  - Sequencing and characterization of the Xenopus laevis ribosomal protein L34 cDNA.
AB  - In this paper, a cDNA homologous to the mammalian ribosomal protein (r-protein)
      L34 was isolated from a Xenopus laevis oocytes library and named XL34. It encodes
      a protein of 116 residues with an Mr of 13.2 kDa and a highly basic sequence. The
      nucleotide (nt) and deduced amino acid (aa) sequence have been compared with the
      L34 sequence from other species. This analysis showed that the L34 is a protein
      greatly conserved from prokaryotes to eukaryotes.XL34 mRNA is abundantly present
      in the whole cytoplasm of oocytes at stages 1 and 2.

PMID- 14585509
TI  - Human disease genes: patterns and predictions.
AB  - We compared genes at which mutations are known to cause human disease (disease
      genes) with other human genes (nondisease genes) using a large set of human
      rodent alignments to infer evolutionary patterns. Such comparisons may be of use
      both in predicting disease genes and in understanding the general evolution of
      human genes. Four features were found to differ significantly between disease and
      nondisease genes, with disease genes (i) evolving with higher
      nonsynonymous/synonymous substitution rate ratios (Ka/Ks), (ii) evolving at
      higher synonymous substitution rates, (iii) with longer protein-coding sequences,
      and (iv) expressed in a narrower range of tissues. Discriminant analysis showed
      that these differences may help to predict human disease genes. We also
      investigated other factors affecting the mode of evolution in the disease genes:
      Ka/Ks is significantly affected by protein function, mode of inheritance, and the
      reduction of life expectancy caused by disease.

PMID- 14585511
TI  - Rampant horizontal gene transfer and phospho-donor change in the evolution of the
      phosphofructokinase.
AB  - Previous work on the evolution of the phosphofructokinase (PFK) has shown that
      this key regulatory enzyme of glycolysis has undergone an intricate evolutionary
      history. Here, we have used a comprehensive data set to address the taxonomic
      distribution of the different types of PFK (ATP-dependent and PPi-dependent ones)
      and to estimate the frequency of horizontal gene transfer (HGT) events. Numerous
      HGT events appear to have occurred. In addition, we focused on the analysis of
      sites 104 and 124 (usually Gly(104)+Gly(124) or Asp(104)+Lys(124)), known to be
      involved in catalysis (J. Biol. Chem. 275 (2000) 35677). It revealed the
      existence of numerous sequences from distantly related species carrying atypical
      combinations of amino acids. Several adaptive changes of phospho-donors, probably
      requiring a single mutation at position 104, have likely occurred independently
      in many lineages. The analysis of this gene suggests the existence of a high rate
      of both HGT and substitution in its active sites. These rampant HGT events and
      flexibility in phospho-donor use illustrate the importance of tinkering in
      molecular evolution.

PMID- 14585510
TI  - The transcriptional regulation of phosphoenolpyruvate carboxykinase gene in the
      kidney requires the HNF-1 binding site of the gene.
AB  - The transcription of the cytosolic form of phosphoenolpyruvate carboxykinase
      (PEPCK-C) gene is differentially regulated in each of the several PEPCK-C
      expressing tissues. In the kidney, it is regulated by glucocorticoids and
      acidosis. Previously, we reported that in LLC-PK1 and derived kidney cell lines,
      mutation of the hepatic nuclear factor 1 (HNF-1) binding site in PEPCK-C gene
      promoter markedly reduced both the basal activity of the gene promoter and its
      response to acidic pH. Using the same kidney cell line, we now report that
      nuclear receptors robustly stimulate transcription from the PEPCK-C gene
      promoter. This stimulation is markedly reduced by mutation of the accessory
      factor 1 (AF1) site in the glucocorticoid responsive unit (GRU) residing within
      the glucocorticoid-responsive domain. The stimulation is likewise reduced by
      mutation of the HNF-1 site, residing outside the nuclear receptor-responsive
      domain of the PEPCK-C gene promoter. There is no binding similarity between HNF-1
      and AF1 binding sites, as is evident from gel shift assays showing a lack of
      competition of either site for the binding of renal nuclear proteins to the
      other. We further assessed that the regulation of PEPCK-C gene transcription by
      acidosis is not mediated by nuclear receptors. This became evident from studies
      of transgenic mice harboring a rat PEPCK-C transgene driven by truncated 5'
      flanking region of the gene, which contains the HNF-1 site but lacks the
      glucocorticoid responsive domain. The full transcriptional response of this
      transgene to acidosis establishes that the truncated 5' flanking region (362 bp)
      of the PEPCK-C gene contains the information required for the acidosis-mediated
      regulation independent of the glucocorticoid domain. Taking together the previous
      and present results, it appears that acidosis and nuclear receptors regulate the
      renal transcription of the PEPCK-C gene via two independent domains in the 5'
      flanking region of the gene. These two modulations, as well as the basal activity
      of the gene, require intact HNF-1 binding site in the gene promoter.

PMID- 14585512
TI  - Opinions on changes in the Romanian health care system from people's point of
      view: a descriptive study.
AB  - After 10 years of changes, the Romanian people were asked to assess the
      consequences of the reforms that were carried out through the health care system
      in the last decennium. This article studies the opinion of changes among
      individuals and socio-economic-demographic groups living in Dolj region. Such
      surveys are rare in Romania. People show to have different opinions on quality of
      care, accessibility and on attitudes of politicians to health care comparing the
      present state of affaires with the past one. Overall the people judge the actual
      situation preferable to the past. The elderly, the chronically ill and the people
      who believe that people were happier 10 years ago have a more critical view on
      the changes especially in terms of accessibility. The higher educated people have
      a more positive opinion on the consequences of the reforms. The results may help
      to improve the communication between policy makers and the population. It is
      suggested that the involvement of the citizens in the health care reforms may
      realize a better implementation of Romanian health care reforms. This involvement
      is lacking.

PMID- 14585513
TI  - Assessing attitude towards prioritizing in healthcare in Iceland.
AB  - The objective of the study was to access the attitude of various groups in
      Iceland towards some prioritizing principles and their application in healthcare.
      The study was a cross-sectional mailing survey including a cover letter and a
      prepaid envelope. It was conducted in Iceland in March through May 1995. There
      were two types of questionnaires, one from a hypothetical patient's perspective
      and the other from hypothetical planners' perspective. Both included the same
      demographic variables. A randomized sample of seven groups were invited to
      participate, i.e. physicians, politicians, and two groups from the general
      public, administrators and board members of health care institutions, registered
      nurses and licensed nurse practitioners. Only findings from the first four groups
      were analyzed and reported here. The response rate ranged from 46 to 75%. On
      average, there was strong reservation against prioritizing between different
      patients groups. However, physicians appear, first, to be more prepared to
      prioritize than other groups, and second, they had a stronger preference to opt
      for effective outcome rather than disease severity. Most respondents were
      reluctant to allocate limited resources to patients who are most seriously ill
      and would receive little benefit from treatment.

PMID- 14585514
TI  - Long-term follow-up and consequences for severe road traffic injuries-treatment
      costs and health impairment in Sweden in the 1960s and the 1990s.
AB  - The purpose of this study is to provide information from two prospective long
      term follow-ups for severe road traffic injuries in Sweden. The long-term
      consequences, in terms of loss of health and costs of care, are presented for
      severe injuries in Sweden in the early 1990s and are compared with information on
      injury severity and health care utilisation 25 years ago. The follow-up in the
      1990s show that, 1 year after the accident 38% of the non-fatal adults were
      suffering of some functional disability, pain and distress. Adults suffering from
      long-term loss of health decreased to 23% on average 3.7 years after the
      accident. The average health care cost was estimated to SEK46200 (in 1995
      prices), and the average in-patient care was 10 days. However, when also
      including subsequent expected life-long care for three severely injured patients,
      the average incidence-based health care cost was estimated to SEK100300. In the 4
      5 year follow-up 25 years ago, severe traffic injuries were treated on average 21
      days in hospital and 38% of the adults were still suffering from long-term
      physical effects. Conclusions to be drawn are that treatment in hospital of
      severe traffic injuries has shortened by half and long-term consequences have not
      been worsened. Our results indicate that long-term effects do not cause as
      serious loss of health nowadays as they did 25 years ago.

PMID- 14585515
TI  - How to minimize inappropriate utilization of Accident and Emergency Departments:
      improve the validity of classifying the general practice cases amongst the A&E
      attendees.
AB  - Studies have found that one-third to two-thirds of all patients attending
      Accident and Emergency (A and E) Departments could be managed appropriately by
      general practitioners (GPs). There is also evidence that referral to GPs can be
      acceptable to patients. The question of primary concern is screening non-urgent
      cases with high degrees of sensitivity (S), specificity (SP), and positive
      predictive value (PPV). This paper reports the findings of the validity (S, SP
      and PPV) of nurses and patients in triaging A and E visitors. A cross sectional
      study was conducted over a 1 year period and subjects were randomly selected from
      four A and E Departments located across the four principle geographic regions of
      Hong Kong by stratified, two-stage sampling. S, SP and PPVs were computed for
      both non-weighted and weighted conditions. The gold standard for defining the
      true urgency status of each selected patient was based on a review of the
      patient's record 3-21 days (or longer if necessary) following the A and E visit.
      The record review in each A and E was blinded and done independently by a panel
      of two (and if disagreement existed, three) senior emergency physicians who did
      not practice in the same hospital. The greatest weights would be for incorrect
      decisions with greatest impact on patients' well being. The most accurate
      unweighted nurses' triage classification had an average sensitivity of 87.8%,
      specificity of 83.9%, and a PPV of 70.1%. When weighted, the average sensitivity
      reduced to 75%, specificity to 65.7%, and PPV to 54%. The most accurate
      unweighted patients' self-triage classification yielded a sensitivity of 62.5%,
      specificity of 69.2%, and a PPV of 58.1%, and correspondingly reduced to 43.3,
      49.2 and 38.6% if weights were applied. Validity of the derived patients' self
      classifications was too inaccurate for practical use. Hong Kong's current use of
      a five-point urgency scale by nurses would be further refined for identifying non
      urgent visitors. If a mechanism was put in place for additional screening on
      visitors with a borderline semi-urgent or non-urgent status, the nurses could
      safely reassign non-urgent patients to GP care. If implemented, a significant
      impact on hospital costs could be realized.

PMID- 14585516
TI  - Drug reimbursement in Finland-a case of explicit prioritizing in special
      categories.
AB  - Increased drug expenses have created challenges for drug reimbursement systems in
      many industrialised countries, including Finland. Prioritization of drugs could
      be one solution to this problem. This paper examines stakeholders' perspectives
      on the prioritization decisions made in the Finnish drug reimbursement system,
      particularly concerning drugs in the higher reimbursement categories. The
      analysis was based on 18 interviews with key stakeholders. The results revealed
      that authorities directly influencing the decisions tried to keep them as
      technical and non-political as possible. However, doing so was not easy, and
      there appeared to be hidden non-technical rationales behind many decisions.
      Stakeholders outside public administration had few opportunities to openly
      participate in decision-making because of the lack of transparency of the
      process. Despite this, they tried to influence decisions concerning their
      interests by using several means, such as lobbying the media, Parliament or other
      stakeholders. Transparent decision-making and better methods of open discussion
      on competing interests could promote democracy in the prioritization of drugs and
      perhaps reduce the harmful effects of indirect and unequal participation by
      different stakeholders.

PMID- 14585517
TI  - The precautionary principle within European Union public health policy. The
      implementation of the principle under conditions of supranationality and
      citizenship.
AB  - The present study examines the precautionary principle within the parameters of
      public health policy in the European Union, regarding both its meaning, as it has
      been shaped by relevant EU institutions and their counterparts within the Member
      States, and its implementation in practice. In the initial section I concentrate
      on the methodological question of "scientific uncertainty" concerning the
      calculation of risk and possible damage. Calculation of risk in many cases
      justifies the adopting of preventive measures, but, as it is argued, the
      principle of precaution and its implementation cannot be wholly captured by a
      logic of calculation; such a principle does not only contain scientific
      uncertainty-as the preventive principle does-but it itself is generated as a
      principle by this scientific uncertainty, recognising the need for a society to
      act. Thus, the implementation of the precautionary principle is also a
      simultaneous search for justification of its status as a principle. This
      justification would result in the adoption of precautionary measures against risk
      although no proof of this principle has been produced based on the "cause-effect"
      model. The main part of the study is occupied with an examination of three cases
      from which the stance of the official bodies of the European Union towards the
      precautionary principle and its implementation emerges: the case of the "mad
      cows" disease, the case of production and commercialization of genetically
      modified foodstuffs. The study concludes with the assessment that the effective
      implementation of the precautionary principle on a European level depends on the
      emergence of a concerned Europe-wide citizenship and its acting as a mechanism to
      counteract the material and social conditions that pose risks for human health.

PMID- 14585518
TI  - The relationship between prevention of mother to child transmission of HIV and
      stakeholder decision making in Uganda: implications for health policy.
AB  - OBJECTIVES: To explore a selection of stakeholders' use of evidence and other
      reasons in the relative ranking of the prevention of mother to child HIV
      transmission with nevirapine in a setting of extreme resource scarcity. DESIGN:
      Group interviews using nominal group technique with provision of evidence.
      SETTING: One rural and one urban district in Uganda. PARTICIPANTS: People living
      with HIV/AIDS, people from the general population, planners, health workers and
      people with hypertension. MAIN OUTCOME MEASURE: relative ranking of prevention of
      vertical HIV transmission with nevirapine compared to nine other interventions
      for different conditions and evaluation of participants' use of evidence in the
      ranking. RESULTS: In the overall final ranking, prevention of vertical HIV
      transmission with nevirapine was ranked as number five compared to the other
      eight conditions. Treatment for childhood diseases and highly active anti
      retroviral treatment (HAART) for HIV/AIDS were ranked higher. Group specific
      ranking followed the same pattern, although the people living with HIV-group
      ranked HAART consistently as number one. CONCLUSIONS: Stakeholders seem to rank
      prevention of vertical HIV transmission lower than treatment for malaria,
      pneumonia and diarrhoea. Policies considering prevention of vertical transmission
      of HIV should consider its implications. This study shows that stakeholders are
      open to considering evidence in assessing the relative priority of different
      interventions competing for scarce resources. More research is needed to develop
      methods that can involve representative stakeholders, including the public, in
      good and legitimate decisions on priorities.

PMID- 14585519
TI  - Impact of different progestins on endometrial vascularisation of postmenopausal
      women. A retrospective image analysis-morphometric study.
AB  - OBJECTIVES: To determine if the vascularisation of the endometrium is dependent
      on the administered progestin during sequential hormone replacement therapy.
      METHODS: Nine women received percutaneous estradiol-17 beta, 1.5 mg/day from days
      1 to 24 combined with 200 mg/day micronised progesterone from days 11 to 24 of
      the treatment cycle. Fifteen women received percutaneous estradiol, 1.5 mg/day
      from days 1 to 24, combined with 10 mg/day chlormadinone acetate from days 11 to
      24. Eleven women received percutaneous estradiol, 50 microg/day from days 1 to 28
      combined with percutaneous norethisterone acetate, 0.3mg/day form days 14 to 28.
      Twelve women received intranasal estradiol, 300 microg/day from days 1 to 25
      combined with 0.5 mg of promegestone from days 11 to 24. Eleven spontaneous
      cycling women had an endometrial biopsy during luteal phase and served as
      controls. Endometrial biopsies were processed routinely between days 18 and 24
      and sections were immunostained using anti-CD34 antibody to identify vascular
      endothelial cells, which were treated with an automatic image analysis system.
      RESULTS: mean (+/-S.D.) vascular density for controls was 147+/-41.5
      vessels/mm(2), with mean vessel area of 143+/-60.9 microm(2). In chlormadinone
      users endometrial microvascular density and mean vessel area did not differ from
      the control group (150.2+/-58.6 and 152.9+/-70.5). The other three progestins
      generated a significant increase of mean vessel density, 179.6+/-51.6 with
      micronised progesterone, 178.5+/-67.6 with norethisterone and 179.6+/-48.4 with
      promegestone. The mean vessel area was lower in the latter three groups,
      respectively, 108.4+/-39.0, 97.5+/-46.5 and 141.6+/-66.7 microm(2), promegestone
      leading to non significant difference with control. CONCLUSION: regarding
      vascularisation, chlormadinone and control group gave similar patterns.
      Promegestone was associated with an increase of the number of vessels, as did
      micronised progesterone or norethisterone; the mean vascular area was the
      smallest in the norethisterone group.

PMID- 14585520
TI  - Dose proportionality study of four doses of an estradiol transdermal system,
      Estradot.
AB  - OBJECTIVES: To establish dose proportionality among four doses of a new estradiol
      transdermal system (ETS), Estradot, in healthy postmenopausal women and to
      evaluate the wear and irritation properties of the ETS. METHODS: In an open
      label, single-dose, randomized, four-period crossover study, healthy
      postmenopausal women, age range 44-64 years, wore four different sizes of
      Estradot, 2.5, 3.75, 5.0 and 10.0 cm(2) that were expected to release estradiol
      at 0.025, 0.0375, 0.05 and 0.10 mg/day, respectively. Each patch was worn for 84
      h with a 7-day washout period between treatments. Blood samples were drawn prior
      to medication, then at various time points following patch application. Serum
      concentrations of estradiol and estrone were determined by validated gas
      chromatography/mass spectrometry (GS/MS) methods. Skin irritation, (erythema and
      edema), patch adherence and local skin reaction were assessed and recorded
      following patch removal. After removal, the patches were assayed for residual
      estradiol to estimate the apparent dose delivered. RESULTS: The baseline
      corrected, mean maximum serum estradiol concentrations (C(max)) for the 2.5,
      3.75, 5.0 and 10.0 cm(2) patches were 24.0, 34.8, 50.1 and 96.0 pg/ml,
      respectively, and for estrone were 10.5, 15.2, 21.8 and 41.0 pg/ml, respectively.
      The four Estradot patches adhered well during the study. No significant skin
      irritation was observed with any of the four treatments. CONCLUSIONS: The results
      indicate a dose proportional relationship of increased serum concentrations of
      estradiol with increasing size of the Estradot patches. The four doses of
      Estradot demonstrated good systemic and local skin tolerability.

PMID- 14585522
TI  - Experience of climacteric symptoms among 42-46 and 52-56-year-old women.
AB  - OBJECTIVE: The intensity of climacteric symptoms and their connection with
      sociodemographic background data were assessed among women who are or will soon
      be menopausal. METHODS: A sample of 5510 Finnish women who were 42-46 or 52-56
      years-old was selected to this 'Quality of Life among Middle-aged Women' Study
      and received a menopause-specific questionnaire. RESULTS: Only 5% of the older
      and 36% of the younger women were totally asymptomatic. Altogether, 2% of the
      younger and 11% of the older women had severe climacteric symptoms. In the
      younger age group, a high symptom intensity was associated with living in town,
      having a low level of professional education, and being unemployed/laid off,
      whereas in the older age group, the experience of severe symptoms was associated
      with those having a couple relationship. CONCLUSION: Altogether 95% of women in
      the productive working age (52-56-years-old) surprisingly suffer from mild,
      moderate, or severe climacteric symptoms. Further even up to 64% of the younger
      women (42-46-years-old) suffered from similar symptoms.

PMID- 14585521
TI  - Comparative bioequivalence studies with Estradot and Menorest transdermal
      systems.
AB  - OBJECTIVES: To compare the relative bioavailability of Estradot, a small size,
      new generation estradiol transdermal system (ETS) to Menorest, in healthy
      postmenopausal women. METHODS: In two open-label, single center, randomized,
      crossover, bioequivalence studies, healthy postmenopausal women aged 40-65 years
      received treatment with all the test regimens. In Study 1 (single-dose study),
      patients wore 5 cm(2) (50 microg/day), 10 cm(2) (100 microg/day) Estradot and 29
      cm(2) (100 microg/day) Menorest for 84 h. In Study 2 (multiple-dose study),
      patients wore a regimen of four consecutive treatments with a 5 cm(2) (50
      microg/day) new generation patch, Estradot and a 14.5 cm(2) (50 microg/day)
      patch, Menorest. Blood samples were drawn at various time-points in both studies.
      Estradiol and estrone serum levels were determined by gas chromatography/mass
      spectrometry or radioimmunoassay methods. Skin irritation (erythema and edema),
      patch adherence and local skin reaction were assessed following patch removal.
      RESULTS: In Study 1, baseline-uncorrected C(max) for estradiol for Estradot 50
      and 100 microg/day and Menorest 100 microg/day was 54.8, 106.2 and 101.6 pg/ml,
      respectively, and C(max) for estrone was 75.6, 97.0 and 98.3 pg/ml, respectively.
      In Study 2, the baseline-uncorrected mean maximum serum concentration (C(max))
      for estradiol for Estradot 50 microg/day and Menorest 50 microg/day patches was
      56.7 and 52.7 pg/ml, respectively, and C(max) for estrone was 41.7 and 41.3
      pg/ml, respectively. No significant skin irritation was observed in either study,
      but Estradot caused less skin irritation than Menorest. CONCLUSIONS: Estradot
      produced comparable serum concentrations of estradiol and estrone and caused less
      skin irritation than Menorest.

PMID- 14585523
TI  - Menopausal status, hormone replacement therapy use and risk of self-reported
      physician-diagnosed osteoarthritis in women attending menopause clinics in Italy.
AB  - OBJECTIVE: In order to offer data on the association between menopausal status,
      hormone replacement therapy use and risk of self-reported physician-diagnosed
      osteoarthritis (OA) in women around menopause, we analyzed information collected
      in the framework of a large epidemiological study conducted in Italy. METHODS:
      Since 1997, a large cross sectional study has been conducting on the
      characteristics of women around menopause attending a network of first level
      outpatients menopause clinics in Italy for general counseling about menopause or
      treatment of menopausal symptoms. Eligible for the study were women consecutively
      observed at the participating centers. Up to March 2000, a total of 42464 women
      (mean age 53 years) were observed. Women were asked, using the same
      questionnaire, about their general characteristics and habits, and if they suffer
      of OA diagnosed by a physician requiring medical or surgical treatment. RESULTS:
      A total of 12521 women reported OA. The risk of OA increased with body mass index
      (BMI), the odds ratio, OR, being for BMI>or equal to 27 versus <24, 1.56 (95%CI
      1.47-1.64). The risk increased with a history of osteoporosis/osteopenia (OR
      1.65, 95%CI 1.57-1.74) and was lower in more educated women (OR high
      school/university degree vs. primary school degree 0.79, 95%CI 0.75-0.84).
      Considering menopausal status, women in spontaneous or surgical menopause were,
      at increased risk of OA (OR 1.13, 95%CI 1.07-1.21, and 1.18, 95%CI 1.08-1.28,
      respectively, in women in surgical and spontaneous menopause). No clear
      relationship, however, emerged with age at menopause. Ever hormonal replacement
      therapy users were at decreased risk of OA, the OR being for ever users in
      comparison with never 0.73 (95%CI 0.69-0.78). CONCLUSION: This analysis gives
      some epidemiological support to the hypothesis that estrogen deficiency may
      increased the risk of OA.

PMID- 14585524
TI  - The effects of hormone replacement therapy type on pulmonary functions in
      postmenopausal women.
AB  - OBJECTIVE: To study whether hormone replacement therapy (HRT) or Tibolone has an
      effect on pulmonary function in postmenopausal women. METHODS: Seventy-five
      postmenopausal women without any risk factor for pulmonary disease were included
      in this randomized, prospective study. Fifty women had undergone natural
      menopause and 25 had had a hysterectomy/ooforectomy. Twenty-five natural
      menopause women were randomly allocated to two groups: 25 patients (Group I) were
      treated with Tibolone 2.5 mg/day, 25 patients (group II) with Estradiol
      Hemihidrate 2 mg+Norethindron Asetate 1 mg/day. Twenty-five induced menopause
      women were treated with 17 beta-estradiol 2 mg/day. Lung function tests including
      forced vital capacity (FVC), forced expiratory volume (FEV(1)), FEV(1)/FVC,
      forced expiratory flow rate over the 25-75% of the forced vital capacity volume
      (FEF(25-75%)), and peak expiratory flow rate (PEF) were evaluated at the
      beginning and 3 months after the treatment to assess the effects of HRT and
      Tibolone on respiratory function. RESULTS: Regardless of HRT types a significant
      difference was observed in FVC and FEV(1) after 3 months of the therapy (P=0.001,
      0.0001, respectively). No significant difference was found between pre and post
      therapy values in the other parameters (P>0.05). CONCLUSIONS: We determined a
      significant increase in FVC and FEV(1) parameters of pulmonary functions after 3
      months of the therapy regardless of HRT types. Therefore, we think that HRT
      regimens have modifying effects on pulmonary function in postmenopausal women.

PMID- 14585526
TI  - Relationship of head lean mass to regional bone mineral density in elderly
      postmenopausal women.
AB  - OBJECTIVES: This study investigated the relationship of head lean mass to bone
      mineral density (BMD). METHOD: Subjects were 102 elderly women (> or =65-years
      old) and 123 middle-aged postmenopausal women (<65-years-old) with right-side
      dominance. Age, height, weight, and years since menopause (YSM) were recorded.
      Lean mass of the head, arm, trunk, leg, and total body were measured by dual
      energy X-ray absorptiometry (DEXA). BMD of the same regions were measured by
      DEXA. RESULTS: In elderly women, head lean mass was positively correlated with
      BMD of the head (r=0.389, P<0.01), left arm (r=0.235, P<0.05), right arm
      (r=0.280, P<0.05), lumbar spine (L2-4) (r=0.411, P<0.001), pelvis (r=0.490,
      P<0.001), left leg (r=0.572, P<0.001), right leg (r=0.558, P<0.001), and total
      body (r=0.529, P<0.001). These relationships remained significant after adjusting
      for age, height, and YSM. In addition, the strength of correlation of head lean
      mass with BMD was higher than those of other regional lean mass with respective
      BMD. In middle-aged women, strength of correlation of head lean mass with BMD was
      loose (r< or =0.238), while regional lean mass was more correlated with
      respective regional BMD. CONCLUSION: Factors related to lifestyle associated with
      higher (lower) head lean mass may contribute to higher (lower) BMD in elderly
      postmenopausal women.

PMID- 14585525
TI  - Effects of estradiol alone or in combination with cyproterone acetate on carotid
      artery pulsatility index in postmenopausal women.
AB  - OBJECTIVES: The incidence of cardiovascular disease (CVD) increases dramatically
      with the loss of ovarian function. Observational studies indicate that the risk
      of CVD may be reduced by up to 50% in postmenopausal women who take estrogen
      replacement therapy. Estrogen therapy reduces internal carotid artery pulsatility
      index (PI). The improvement in carotid PI following HRT has been proposed as a
      marker of the cardioprotective effect of estrogen therapy. Cyclical progesterone
      addition to ERT partially antagonizes the reduction on the carotid artery PI. As
      progesterone, androgens has been shown to decreases arterial vasodilatation and
      carotid PI. To our knowledge no information is available regarding the effect of
      CPA addition on the carotid artery PI in women taking estrogen replacement
      therapy. METHODS: We recruited a total of 30 women in postmenopause for at least
      12 months and were in good health. Fifteen women were postmenopausal following
      surgical bilateral oophorectomy for benign condition. Fifteen postmenopausal
      women received estradiol valerate for 21 days and CPA (1 mg) for 10 days for 3
      months (Group E/CPA). Ovarectomized women (n=15) received estradiol hemihydrate
      (2 mg) for 3 months (Group E). The main factor investigated was PI, an indicator
      of impedence to blood flow down stream. Doppler US were performed before the
      start and at the end of the therapy. RESULTS: The mean reductions respect to
      basal values were 11.5% in women treated with E and 10.8% in women treated with
      E/CPA. No significant difference was found between treatment values. CONCLUSIONS:
      The results of the present study demonstrate that cyproterone acetate addition to
      E do non-antagonize the effect of estrogen on carotid artery PI. The present
      study demonstrate that both estradiol hemihydrate and estradiol valerate plus
      cyproterone acetate lead to similar improvement in carotid artery; through this
      mechanism both treatments could potentially reduce the incidence of
      cerebrovascular disease in postmenopausal women.

PMID- 14585527
TI  - Central and peripheral temperature changes in sheep following ovariectomy.
AB  - OBJECTIVES: To determine if ovariectomized ewes undergo periodic body temperature
      rises (hot flashes) similar to women at menopause. METHODS: Eighteen mature ewes
      were assigned to ovariectomy (OVX), ovariectomy+17 beta-estradiol implant (OVXE)
      or Sham. Electronic temperature loggers placed subcutaneously over the carotid
      artery and within the abdomen (core) and subcutaneously in the thigh and axilla
      (peripheral) were programmed to record body temperatures every 2.5 min for 59
      days. Circadian rhythm changes were avoided by dividing readings into 1 h
      intervals. Hot flashes were defined as a 0.2 or 0.4 degrees C increase over the
      minimum temperature recorded for a 1 h interval for each sheep. RESULTS: Logger
      placement did not reflect core and peripheral temperatures. The carotid and
      abdominal sites were most useful. The percentage of readings considered HF at the
      carotid site was 63% OVX, 54% OVXE and 37% Sham (P<0.001), and at the abdominal
      site were 32% OVX, 15% OVE and 17% Sham (P<0.001). When only the first 7 days
      after ovariectomy were analyzed, the percentage of readings considered to be HF
      at the carotid site was 75% OVX, 63% OVXE, and 49% Sham (P<0.001), and at the
      abdominal site was 35% OVX, 15% OVXE and 17% Sham (P<0.001). CONCLUSIONS:
      Ovariectomy in the ewe does illicit changes in body temperature compared with
      control ewes, which may be interpreted as HF. However, shifts in the circadian
      rhythm were not apparent. Estradiol treatment led to milder and less frequent HF.
      Periodic HF in species other than rats have heretofore not been reported.

PMID- 14585528
TI  - Endometriosis arising during estrogen and testosterone treatment 17 years after
      abdominal hysterectomy: a case report.
AB  - OBJECTIVE: To report the possible association between the use of oestrogen
      replacement therapy and endometriosis in a postmenopausal woman. METHODS: We
      present a case of a postmenopausal, previously hysterectomised, woman who
      received hormonal replacement therapy and developed a large broad ligament cyst.
      Two years prior to her presentation she had been complaining of pelvic pain and
      deep dyspareunia. RESULTS: Pelvic ultrasound showed an adnexal cyst that was
      increasing in size. CA-125 was normal. Laparoscopy revealed multiple
      endometriotic deposits and a broad ligament cyst. Cystectomy and oophorectomy
      were done. Histology confirmed a diagnosis of endometriosis including the broad
      ligament cyst. CONCLUSIONS: Hormonal replacement therapy can be associated with
      de novo endometriosis including at sites, which are unusual.

PMID- 14585529
TI  - [The concept of handicap].
AB  - The notion of disability appears recently in the medical and medico-legal field.
      It is the origin of a fundamental discussion about the health, and an ethical
      debate about human person. Indeed it drives to identify among the health users a
      particular group: disabled persons for whom the methods used with success in the
      field of diseases are not convenient. For ethical point of view: it is the
      identity of the person in a situation of disability, its dignity, its self-esteem
      and the respect through the regard of others which are in question. The debate
      was amplified when the project of a classification of handicap, as consequences
      of diseases, (Wood, WHO) was published, in 1980. Two tendencies were in
      opposition: one of them is "medicinal", following the opinion of Wood, the second
      is "anthropological and social", supported by scientific and disabled
      associations. The first proposition of Wood, after a long discussion, is
      abandoned. It is replaced by a "Classification of functioning, disability and
      health", adopted by the Mondail assembly of WHO in May 2002. This device is a
      compromise between the precedent tendencies. This document is heavy, confusing,
      imprecise and very difficult to use. We suggest a definition with dimensions,
      separating clearly the body modifications, the universal functional capacities
      for a human person and the situations of life. The subjectivity is individualised
      as a special dimension of assessment.

PMID- 14585530
TI  - [Personal experience of children with a brain injured parent: preliminary study].
AB  - OBJECTIVE: To explore the impact of the brain injury of a parent on his child's
      behavioural and emotional symptoms and personal experience. PATIENTS AND SETTING:
      Nineteen children from 6 to 12 years old at the time of the research having a
      brain-injured parent living at home and with cognitive impairments. MAIN OUTCOME
      MEASURES: Case report. Assessment of a questionnaire measures of anxiety, the R
      CMAS scale. Qualitative analysis of a semi-structured interview and of the family
      drawing. RESULTS: Four children (21%) presented pathological anxiety assessed by
      the R-CMAS scale. The analysis of the semi-structured interview showed that 16
      children had a representation of the brain injury. The symbolic place of the
      brain-injured parent was maintained for all the children and one presented
      impulsive behaviours. The family drawing analysis showed the lack of relational
      interaction between the family members in 16 cases (84%). Three children (15%)
      represented the real disability, and 17 (89%) abnormalities in the bodies'
      pictorial representation of the personages. These abnormalities concerned the
      brain-injured parent and the other members of the family. A characteristic sign
      was the lack of hands or the representation of amputee hands in 14 cases (73%).
      Another one was the unsteadiness of family members, who were also represented as
      ghosts or "in the air" in 13 cases (68%). CONCLUSION: Children seem adapted and
      they have few emotional and behavioural disorders. But there was a strong impact
      of the disability of the parent on their personal experience and on their
      perception of "the family body".

PMID- 14585531
TI  - [Determination of an expected plantar pressure threshold: dimensionless approach
      use to reduce the variability of the plantar pressures].
AB  - OBJECTIVE: The aim of this study was to verify that the determination of walking
      velocities proportional to the leg lengths of the subjects together with the
      dimensionless expression of the results enable us to decrease the variability and
      to determine a plantar pressure threshold. MATERIALS AND METHODS: Fifteen male
      subjects performed two walking tests on a treadmill at imposed velocities (V1 and
      V3) and similar velocities (V27 and V37). Similar velocities (Vsim
      =Nfr(g.Li)(0.5)) were determined from two fractions of the Froude number (Nfr),
      the gravitational acceleration (g) and the length of the lower limb (Li) of the
      subjects. An in-shoe plantar pressure measurement system allowed the pressure
      peaks to be recorded. The peak of pressure (p) was reported to the step length
      (a) and the weight of the subject (mg) for the dimensionless pressure peaks
      (Dim(P)=p.a2/mg) to be expressed. The coefficients of variability (CoV) and
      extends of the dimensionless pressure peaks (Epp) have been studied at the
      different imposed walking velocities. RESULTS: The CoV and Epp of the
      dimensionless pressure peaks recorded at V27 and V37 (similar velocities) are
      from 2 to 9% and 3 to 22% lower than those observed at V1 and V3, respectively.
      DISCUSSION-CONCLUSION: The analysis of the pressure peaks CoV and Epp shows that
      the method should allow a data bank usable to detect the effects of a disability
      on the plantar pressures to be elaborated. Indeed, our results enable us to
      define a plantar pressure pattern with a variability lower than those reported in
      most scientific articles.

PMID- 14585532
TI  - [Strength training with elastic bands: measure of its effects in cardiac
      rehabilitation after coronary diseases].
AB  - OBJECTIVES: To compare high intensity strength training with weightlifting
      exercises or with elastic bands. SETTING: Outpatient unit of cardiac
      rehabilitation. TYPE: Prospective randomised clinical trial. POPULATION:
      Inclusion of coronary patients in phase II after medical or surgical treatment of
      a myocardiac infarction, without cardiac insufficiency; beta-blockers were
      accepted. METHOD: Evaluation of coronary patients at beginning and at the end of
      a 4 week cardiac rehabilitation program. It included progressive aerobic training
      according to Karvonen method for all the patients, associated with weightlifting
      exercises (Koch press) in the control group, or use of elastic bands in the
      experimental group. Cardiac rate, oxygen consumption at rest and at maximum power
      were the main criteria with also muscle strength of quadriceps, hamstrings,
      biceps brachii, latissimus dorsi and triceps brachii, body mass indexes, quality
      of life with SF-36, anxiety (stay T test) and perceived exertion with the Borg 10
      point category-ratio scale, myotendinous injuries (Shaw scale). RESULTS: Twenty
      six coronary patients, all male from 45 to 65 years old, all receiving beta
      blockers, were included, 13 in each group. Control and experimental groups were
      initially similar. At the end of the 4 week program, all the two groups improved
      significantly their strength and power and there were no differences between the
      two groups. Perceived exertion was lower in the group using elastic bands and
      there were no myotendinous lesions. CONCLUSION: Strength training with elastic
      bands is a low-cost, attractive, playful technique, proposed to a group of
      coronary patients, which appears as effective in cardiac rehabilitation as
      individual weightlifting training.

PMID- 14585533
TI  - [French translation and cultural adaptation of the "Back Book"].
AB  - OBJECTIVES: To develop an information booklet for French speaking low back pain
      patients, promoting staying active as a single treatment for low back pain.
      MATERIALS AND METHODS: A four-step procedure was used to obtain the information
      booklet. Selection of a booklet using a literature search and pre-defined
      criterias. Translation/back-translation technique with a method used for health
      related quality of life cross-cultural adaptation method. Content validity
      assessment by a knowledge questionnaire submitted to 32 low back pain patients
      hospitalized for treatment and a review by two independent MD. Check accordance
      of the translated document with original authors and editor guidelines. RESULTS:
      The use of a standardized translation/back-translation procedure permitted to
      obtain a translation of the back book suitable for French patients. The
      significant improvement (P = 10(-6)) in patients' knowledge confirmed the quality
      of the translation. CONCLUSIONS: Translation and cultural adaptation of an
      information booklet should allow cross-cultural studies in the field of
      information for low back pain patients.

PMID- 14585534
TI  - [Information provided to the lowback pain patient].

PMID- 14585536
TI  - Apoptosis: from regulation to infection.

PMID- 14585537
TI  - Serine/threonine protein phosphatases PP1 and PP2A are key players in apoptosis.
AB  - The reversible phosphorylation of proteins controlled by protein kinases and
      protein phosphatases is a major mechanism that regulates a wide variety of
      cellular processes. In contrast to C. elegans, recent studies in mammalian cells
      have highlighted a major role of serine/threonine protein phosphorylation in
      apoptosis. To illustrate the importance of dephosphorylation processes in
      apoptosis, this review will focus on recent studies suggesting that the
      interaction of the serine/threonine protein phosphatase 1 (PP1) and protein
      phosphatase 2A (PP2A) with certain regulators of the Bcl-2 family is critically
      involved in the control of apoptosis.

PMID- 14585538
TI  - Rafts: a simple way to control apoptosis by subcellular redistribution.
AB  - Apoptosis is an essential feature of development and homeostasis in higher
      organisms. Lipid rafts are subdomains of the plasma membrane that contain high
      concentrations of cholesterol and sphingolipids. In response to intra or
      extracellular stimuli, lipid rafts can include or exclude proteins to variable
      extents. This favors specific protein-protein interactions and modulates the
      activity of signaling cascades. Recently, a number of proteins involved in
      apoptotic signals have been located in lipid rafts. Among these proteins is
      included Bad, a pro-apoptotic molecule belonging to the Bcl-2 family. Bad is
      attached to lipid rafts in proliferating cells while associated to mitochondria
      in apoptotic cells, suggesting that the interaction of Bad with rafts is a
      dynamic process involved in the control of apoptosis. In this review, we briefly
      summarize the structure of rafts and illustrate their contribution to the control
      of apoptosis.

PMID- 14585539
TI  - Changes in bad phosphorylation are correlated with BCR-induced apoptosis of WEHI
      231 immature B cells.
AB  - Signaling through the B cell antigen receptor (BCR) is a key determinant in the
      regulation of B cell physiology. Depending on additional factors, such as
      microenvironment and developmental stage, ligation of the BCR can trigger B
      lymphocyte activation, proliferation, or apoptosis. The regulatory mechanisms
      determining B cell apoptosis and survival are not completely known. Using the
      murine B lymphoma cell line WEHI-231 as a model system, we investigated the role
      of Bad phosphorylation, a pro-apoptotic member of the Bcl-2 family, in anti-IgM
      mediated apoptosis. For apoptotic analysis we focused in particular on the
      mitochondrial potential (deltapsi(m)) collapse which has been reported as a rate
      limiting step in the BCR-induced cell death of immature B lymphocytes. Bad
      phosphorylation at serine 112, 136 and 155 was found in WEHI-231 cell control
      cultures and its hypophosphorylation on the three sites correlated with the
      appearance of apoptosis when cross-linking surface IgM. Furthermore, treatment of
      cells with specific PK inhibitors known to be involved in serine phosphorylation
      of Bad (LY294002 for PI3K and H-89 for PKA) mimiced or enhanced BCR-induced cell
      death. These results strongly suggest that regulation of Bad phosphorylation
      plays an active role in mediating anti-IgM-induced apoptosis of immature B cells.

PMID- 14585540
TI  - Mitochondrial dysfunction in CD47-mediated caspase-independent cell death: ROS
      production in the absence of cytochrome c and AIF release.
AB  - Ligation of CD47 by its natural ligand thrombospondin (TSP), or cross-linking by
      CD47 antibodies, triggers caspase-independent cell death in normal and leukemic
      cells. This kind of cell death is characterised by the cytoplasmic events of
      apoptosis including externalisation of phosphatidylserines and mitochondria
      swelling. We report herein selective mitochondrial changes in CD47-dependent cell
      death of T cells. After T cell stimulation via CD47, a rapid mitochondrial
      transmembrane potential (deltapsi(m)) disruption is accompanied by the production
      of reactive oxygen species (ROS) and phosphatidylserine exposure. Surprisingly,
      mitochondrial dysfunction does not induce cytochrome c or AIF release. Moreover,
      the dying cells do not exhibit caspase-3 activation and display intact nuclei
      without any large-scale, or oligonucleosomal DNA fragmentation. We conclude that
      DeltaPsi(m) loss and ROS production are an early step in CD47-dependent killing
      and neither cytochrome c, nor AIF are implicated in this new cell death pathway.

PMID- 14585541
TI  - A role for AP-1 in apoptosis: the case for and against.
AB  - The nuclear transcription factor AP-1, composed of dimers of Fos and Jun
      proteins, has been linked to a startling breadth of cellular events including
      cell transformation, proliferation, differentiation and apoptosis. AP-1 is often
      portrayed as a general, nuclear decision-maker that determines life or death cell
      fates in response to extracellular stimuli. However, it is increasingly clear
      that the cellular context is critical for determining the contribution of AP-1 to
      cellular fates, and the role of AP-1 in apoptosis should be considered within the
      context of a complex network of nuclear factors that respond simultaneously to a
      wide range of signal transduction pathways. We take a closer look at the evidence
      for and against a role for AP-1 in inducing apoptosis, drawing on examples of
      studies in neurons, lymphocytes and hepatocytes. Although AP-1 activation is
      associated with a large number of apoptotic scenarios, its role in ensuring cell
      survival seems equally important. It is, therefore, difficult to convict AP-1 as
      a killer without taking into account the cellular and extracellular context
      within which it is functioning. Defining the target genes regulated by AP-1 in
      these different contexts will help to decipher the contribution of AP-1 to cell
      fate decisions.

PMID- 14585542
TI  - Protein phosphatase 2A as a new target for morphogenetic studies in the chick
      limb.
AB  - The family of ser/thr protein phosphatases 2A (PP2A) is a major regulator of cell
      proliferation and cell death and is critically involved in the maintenance of
      homeostasis. In order to analyse the importance of PP2A proteins in apoptotic and
      developmental processes, this review focuses on previous studies concerning the
      role of PP2A in morphogenesis. We first analyse wing formation in Drosophila, a
      model for invertebrates, then chick limb bud, a model for vertebrates. We also
      present a pioneer experiment to illustrate the potential relevance of PP2A
      studies in BMP signalling during chicken development and we finally discuss the
      BMP downstream signalling pathways.

PMID- 14585543
TI  - Cell death and inflammation during infection with the obligate intracellular
      pathogen, Chlamydia.
AB  - Infections by Chlamydia are followed by a strong inflammatory response, which is
      necessary to eliminate the infection, but at the same time is responsible for the
      pathology of infection. Resistance of infected cells against apoptosis induced by
      external ligands, together with the effects of IFNgamma secreted during
      infection, would be expected to contribute to persistence of infection. Secretion
      of TNFalpha plays an important role during clearance of the chlamydiae, but also
      triggers apoptosis of uninfected cells in infected tissues. Apoptosis of infected
      host-cells towards the end of the infection cycle is thought to participate in
      the release of chlamydiae from infected cells and propagation of the infection.
      Dysregulation of the apoptotic program during infection leads to a less efficient
      infection, but paradoxically, results in a higher inflammatory response and more
      severe pathology.

PMID- 14585544
TI  - Apoptosis of Theileria-infected lymphocytes induced upon parasite death involves
      activation of caspases 9 and 3.
AB  - The intracellular parasite Theileria parva (T. parva) can infect bovine B and T
      lymphocytes. T. parva-infected cells become transformed, and they survive and
      proliferate independently of exogenous growth factors. In vivo the uncontrolled
      cellular proliferation associated with lymphocyte transformation underlies the
      pathogenesis of the disease called East Coast Fever. The transformed state of
      parasitised cells can be reversed upon elimination of the parasite by specific
      theilericide drugs. In this study we found that elimination of the parasite by
      buparvaquone induces apoptosis of transformed B and CD8(+) T-lymphocytes.
      Apoptosis is accompanied by the activation of caspase 9 and caspase 3 and
      processing of poly(ADP ribose) polymerase and is inhibited by Z-VAD a general
      caspase inhibitor. Based on these observations, we propose that the lack of
      activation of a caspase 9 > caspase 3 > poly(ADP ribose) polymerase pathway is
      important and protects T. parva-transformed cells from spontaneous apoptosis.

PMID- 14585546
TI  - Expression of dengue ApoptoM sequence results in disruption of mitochondrial
      potential and caspase activation.
AB  - Apoptotic cell death has been involved as a cytopathologic mechanism in response
      to dengue (DEN) virus infection. Little information exists about how DEN virus
      replication triggers apoptosis in infected cells. We reported that a nine-residue
      sequence of the DEN M protein referred to as ApoptoM has proapoptotic properties
      in transformed and tumor cells of various origins. The aim of the present study
      was to investigate whether ApoptoM-induced apoptosis is associated to
      mitochondrial dysfunction and requires caspase activation. Intracellular
      expression of ApoptoM provokes the disruption of the mitochondrial transmembrane
      potential without subsequent generation of reactive oxygen species. We showed
      that ApoptoM-induced apoptosis involves the activation of a caspase-like protease
      pathway. Caspase-3 like activity was detected in ApoptoM-expressing cells.
      However, there was no role for caspase-9 in ApoptoM-mediated cell death. Our data
      suggest that a particular mitochondrion-dependent apoptotic pathway may be
      involved in induction of apoptosis by ApoptoM.

PMID- 14585545
TI  - Apoptosis and rabies virus neuroinvasion.
AB  - Rabies virus (RV) causes a non-lytic infection of neurons leading to a fatal
      myeloencephalitis in mammals including humans. By comparing the infection of the
      nervous system of mice by a highly pathogenic neuroinvasive strain of RV (CVS)
      and by a strain of attenuated pathogenicity (PV) with restricted brain invasion,
      we showed that RV neuroinvasiveness results of three factors: not only
      neurotropic RV avoids induced neuron cell death but also "protective" T cells
      that migrate into the infected nervous system are killed by apoptosis and finally
      inflammation of the infected nervous system is limited. Our data suggest that the
      preservation of the neuronal network, the limitation of the inflammation and the
      destruction of T cells that invade the CNS in response to the infection are
      crucial events for RV neuroinvasion and for transmission of RV to another animal.

PMID- 14585547
TI  - Intrinsic and extrinsic pathways signaling during HIV-1 mediated cell death.
AB  - Infection with human immunodeficiency virus (HIV) is characterized by the gradual
      depletion of CD4+ T lymphocytes. The incorporation of the concept of apoptosis as
      a rationale to explain progressive T cell depletion has led to growing research
      in this field during the last 10 years. In parallel, the biochemical pathways
      implicated in programmed cell death have been extensively studied. Thus, the
      influence of mitochondrial control in the two major apoptotic pathways-the
      extrinsic and intrinsic pathways-is now well admitted. In this review, we
      summarized our current knowledge of the different pathways involved in the death
      of T cells in the course of HIV infection.

PMID- 14585549
TI  - Validation of a modified Rotterdam Symptom Checklist for use with cancer patients
      in the United States.
AB  - The Rotterdam Symptom Checklist (RSCL) is a well-known instrument for the
      assessment of symptom-related distress among cancer patients. Despite its broad
      application, the utility of the RSCL with patients of some cancers is hindered by
      the omission of several important physical symptoms and methodological
      limitations of previous validation studies. The aims of the present study were to
      modify the RSCL through the addition of several physical symptoms and to
      subsequently validate the modified version of the Rotterdam Symptom Checklist
      (RSCL-M) with a heterogeneous sample of cancer patients from the United States. A
      total of 1,005 male and female cancer patients from two midwestern states
      completed the RSCL-M and several other self-report instruments. Results indicated
      that the RSCL-M is a reliable and valid instrument for use with cancer patients
      in the United States and is sensitive to differences in physical distress across
      groups expected to have distinct symptom-related distress profiles.

PMID- 14585548
TI  - The regulatory E2 proteins of human genital papillomaviruses are pro-apoptotic.
AB  - Cervical carcinomas are frequently associated with infection by human
      papillomaviruses (HPVs). These viruses encode two oncogenes E6 and E7, which
      promote cell proliferation and immortalization. The viral E2 protein represses
      transcription of the E6/E7 oncogenes and activates viral DNA replication together
      with the viral E1 helicase. The E2 protein is specifically inactivated in HPV18
      associated carcinoma, suggesting that it may prevent carcinogenic progression.
      Indeed, E2 was shown to exhibit a strong anti-proliferative action when
      ectopically expressed in cervical carcinoma cells, as it induces both G1 cell
      cycle arrest and cell death by apoptosis. While the cell cycle arrest is due to
      E2-mediated transcriptional repression of the viral oncogenes, the induction of
      apoptosis appears to be an autonomous function of E2. The amino-terminal
      transactivation domain (TAD) of the E2 protein is required for its pro-apoptotic
      activity, but transcriptional transactivation is not involved. E2 induces
      apoptosis through the extrinsic pathway, involving the initiator caspase 8. In
      addition, E2 is cleaved by caspases during apoptosis, providing an example of an
      apoptotic inducer, which is itself a target for caspase cleavage. The cleaved E2
      protein exhibits an enhanced apoptotic activity, suggesting that it may
      participate in an amplification loop. This article reviews our current knowledge
      of the pro-apoptotic activity of the oncogenic papillomavirus E2 proteins, and
      discusses the implications for the viral vegetative cycle.

PMID- 14585550
TI  - A phase II trial of Reiki for the management of pain in advanced cancer patients.
AB  - This trial compared pain, quality of life, and analgesic use in a sample of
      patients with cancer pain (n=24) who received either standard opioid management
      plus rest (Arm A) or standard opioid management plus Reiki (Arm B). Participants
      either rested for 1.5 hr on Days 1 and 4 or received two Reiki treatments (Days 1
      and 4) one hour after their first afternoon analgesic dose. Visual analogue scale
      (VAS) pain ratings, blood pressure, heart rate, and respirations were obtained
      before and after each treatment/rest period. Analgesic use and VAS pain scores
      were reported for 7 days. Quality of life was assessed on Days 1 and 7.
      Participants in Arm B experienced improved pain control on Days 1 and 4 following
      treatment, compared to Arm A, and improved quality of life, but no overall
      reduction in opioid use. Future research will determine the extent to which the
      benefits attributed to Reiki in this study may have been due to touch.

PMID- 14585551
TI  - The problem of assessment bias when measuring the hospice effect on nursing home
      residents' pain.
AB  - This study examined the observed differential documentation of pain on nursing
      home (NH) resident assessments (minimum data sets [MDS]) when dying residents
      were and were not enrolled in hospice. We studied 9,613 NH residents who died in
      6 states in 1999 and 2000. Documented pain was compared among three groups of
      residents who were categorized by their hospice exposure. At the time of their
      last MDS completion, residents in hospice were more likely to receive opioids for
      their moderate to severe pain than were non-hospice residents and residents
      enrolled in hospice after the last MDS assessments. However, hospice residents
      were twice as likely as non-hospice residents and 1.3 times as likely as
      residents who eventually enrolled in hospice to have pain documented. These
      counterintuitive findings suggest that there is differential documentation of
      pain on the MDS when hospice is involved in care, perhaps because of superior
      pain assessment by hospice.

PMID- 14585552
TI  - Patient perceptions of an outpatient palliative care intervention: "It had been
      on my mind before, but I did not know how to start talking about death...".
AB  - Little is known about whether introducing palliative care to seriously ill
      outpatients continuing to pursue treatment of their disease is acceptable or
      beneficial to patients. Intervention patients in a trial of outpatient palliative
      care consultation completed structured exit interviews as part of a qualitative
      study. Participants had advanced heart or lung disease or cancer, and a life
      expectancy between 1 to 5 years as estimated by their primary care physician
      (PCP). Thirty-five of 50 intervention patients (70%) completed the final
      interview. Twenty-one patients (60%) reported that the team uncovered previously
      undiagnosed medical problems, 12 patients (34.3%) reported decreased primary care
      visits, and 8 (22.9%) reported avoiding emergency department visits. Most
      patients reported improved satisfaction with family caregivers (85.7%), PCPs
      (80%), and the medical center (65.7%). Most patients (68.6%) would have wanted
      the intervention even earlier in the course of their illness. Seriously ill
      outpatients found palliative care acceptable and helpful, reporting increased
      satisfaction and decreased health care utilization.

PMID- 14585553
TI  - Are nurses prepared to manage cancer pain? A national survey of nurses' knowledge
      about pain control in Taiwan.
AB  - Nurses play a crucial role in cancer pain control, but little is known about how
      well-prepared nurses are to manage cancer pain in Taiwan. The purpose of this
      study was to examine the level of knowledge about pain management among Taiwanese
      nurses with different background characteristics and to determine the
      predictor(s) of nurses' pain management knowledge. Nurse subjects were recruited
      by a cross-sectional nationwide survey with stratified sampling from nine
      hospitals distributed in the four major geographic regions of Taiwan. The Nurses'
      Knowledge and Attitudes Survey-Taiwanese version (NKAS-T) and a background
      information form were used to collect the data. Of 1900 surveys distributed, 1797
      valid questionnaires (94.5%) were analyzed. The average correct response rate was
      50.5%, with rates ranging from 7-86% for each survey question. Results from
      stepwise regression showed that nurses with higher mean correct answer scores had
      BS or higher degrees, had received pain education at professional conferences,
      had more prior hours of pain education, had longer clinical care experiences, and
      always worked with cancer patients. Nurses who worked in intensive care units,
      however, had significantly lower mean correct scores. The results strongly
      suggest an urgent need to strengthen pain education in Taiwan. The results also
      provide the direction for developing pain education.

PMID- 14585554
TI  - Comparative efficacy and safety of long-acting oral opioids for chronic non
      cancer pain: a systematic review.
AB  - Opioids have been endorsed as appropriate treatment for refractory chronic non
      cancer pain when used according to published guidelines. They are widely used for
      this indication. However, there appear to be gaps in our understanding of the
      efficacy and safety of individual long-acting opioids compared to each other or
      as a class compared to short-acting opioids. This systematic review summarizes
      and assesses the evidence for the comparative efficacy and safety of long-acting
      opioids in the management of chronic non-cancer pain. Randomized trials (for
      comparative efficacy and adverse events) and observational studies (for adverse
      events only) that included non-parenteral long-acting opioids were sought using
      electronic databases, handsearching reference lists, and soliciting
      pharmaceutical company submissions. Searches were performed through October 2002.
      The validity of each included study was assessed using a data abstraction form
      and predefined criteria. An overall grade was allocated for the body of evidence
      for each key question. A total of 16 randomized trials (comparative efficacy and
      adverse events), enrolling 1427 patients, and 8 observational studies (adverse
      events) of 1190 patients were included in this review. No randomized trial was
      rated good quality; observational studies were generally of poorer quality than
      the trials. There was insufficient evidence to prove that different long-acting
      opioids are associated with different efficacy or safety profiles. There was also
      insufficient evidence to determine whether long-acting opioids as a class are
      more effective or safer than short-acting opioids. A subgroup of three studies on
      long-acting versus short-acting oxycodone was more homogeneous and provided fair
      evidence that these formulations are equally effective for pain control.

PMID- 14585556
TI  - Hypogonadism and sexual dysfunction in male cancer survivors receiving chronic
      opioid therapy.
AB  - The purpose of this study was to determine the prevalence of central hypogonadism
      and sexual dysfunction in male cancer survivors exposed to chronic high-dose oral
      opioid therapy. We studied 20 male patients with cancer-related chronic pain who
      were disease-free for at least one year. All patients consumed at least 200 mg
      equivalent of morphine on a daily basis for at least one year. Participants
      completed the Sexual Desire Inventory questionnaire and serum levels of
      testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH)
      were assessed. Serum testosterone levels were reduced in these patients. The
      median value was 140 ng/dL (normal 241-827). There was no compensatory increase
      in FSH and LH. The median FSH level was 3.5 mIU/mL (normal 1.4-18.1). The median
      LH level was 2.1 mIU/mL (normal 1.5-9.3). The mean dyadic sexual desire score was
      23.9+/-15.7 (normal value, 42.8+/-8.9). The mean solitary sexual desire score was
      1.3+/-1.9 (normal value, 10.6+/-1.9). Our data suggest that chronic exposure to
      high-dose oral opioid therapy may result in marked central hypogonadism and
      sexual dysfunction. Given the increasing use of long-term opioid therapy for
      chronic pain syndromes, further investigation into these findings is warranted.

PMID- 14585555
TI  - The effect of donepezil on sedation and other symptoms in patients receiving
      opioids for cancer pain: a pilot study.
AB  - Opioid-induced sedation is a major complication in patients with cancer pain.
      This study assessed the effectiveness of donepezil in opioid-induced sedation and
      related symptoms in patients with cancer pain. Twenty-seven patients who were
      receiving strong opioids for pain and reported sedation were enrolled. Donepezil
      5 mg was given every morning for 7 days. Changes between baseline and Day 7 in
      sedation, pain, fatigue and other symptoms were evaluated using the Edmonton
      Symptom Assessment Scale. Fatigue was also measured using the Functional
      Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue). Overall usefulness
      of donepezil was measured by the patient at the end of the study. In 20 evaluable
      patients, sedation, fatigue, anxiety, well-being, depression, anorexia and
      problems with sleep were significantly improved. Side effects included nausea,
      vomiting, diarrhea, muscle and abdominal cramps, and anorexia. Overall, however,
      the treatment was well tolerated. Donepezil appears to improve sedation and
      fatigue in patients receiving opioids for cancer pain. Randomized controlled
      trials of this agent are justified.

PMID- 14585561
TI  - Diagnosis and follow-up of minor cervical trauma.
AB  - In order to evaluate sensitivity, specificity and accuracy of radiographic
      findings, 1347 patients with minor cervical injury underwent clinical,
      orthopaedic, neurosurgical examination, and were classified as monosymptomatic
      (only cervical pain) or polysymptomatic (cervical pain plus additional symptoms).
      X-rays were taken in anteroposterior, lateral and open-mouth views; additional
      views if necessary. X-ray outcome was normal in 69.8% of monosymptomatic patients
      and there were no fractures. In 45.1% of polysymptomatic patients, outcome was
      normal, but there were seven fractures. Computed tomography/magnetic resonance
      (CT/MR) was performed in patients with documented injury and/or strong persistent
      symptoms. X-ray follow-up at 4-6 weeks included flexion-extension examination.
      Elevated statistical radiographic values were reached. All patients with minor
      cervical trauma should undergo clinical, neurosurgical and three-view
      radiographic follow-up. A simplified algorithm could lead to substantial savings
      and decrease patients' exposure to radiation.

PMID- 14585562
TI  - Magnetic resonance evaluation of fibrovascular ingrowth into porous polyethylene
      orbital implant.
AB  - We assessed the fibrovascular ingrowth into porous orbital implant with MRI.
      Twelve cases underwent T1WI, T2WI, Gd-enhanced T1WI, and Short Tau Inversion
      Recovery (STIR) images. Gd-enhanced T1WI showed homogeneous enhancement (n=4),
      peripheral and posterior part enhancement (n=7), and anterior part enhancement
      (n=1) of implants. High signal intensity portions on STIR images coincided with
      the enhancing portions on Gd-enhanced T1WI. Gd-enhanced T1WI is an excellent
      method for assessment of fibrovascular ingrowth into orbital implant and STIR
      images may be a comparable method to Gd-enhanced T1WI.

PMID- 14585563
TI  - Open-mouth versus closed-mouth radiographs of the nasopharynx in the evaluation
      of nasopharyngeal airway obstruction.
AB  - The open-mouth and closed-mouth nasopharyngeal airway radiographs of 53 children,
      whose symptomatology score was concordant with nasopharyngeal airway obstruction
      that may be due to adenoidal enlargement, were taken and, for each radiograph,
      nasopharyngeal airway/soft palate (NA/SP) ratio was measured and graded using the
      method of Cohen and Konak. According to the statistical analysis, since closed
      mouth views correlated better with the symptomatology score than the open-mouth
      views, if a radiological measurement is needed to evaluate the nasopharyngeal
      airway obstruction, closed-mouth views can be chosen.

PMID- 14585564
TI  - Primary non-Hodgkin's lymphoma of the temporal bone. CT findings.
AB  - We present a 15-year-old male with primary non-Hodgkin's lymphoma (NHL) of the
      temporal bone. Bone erosion and epidural mass seen on CT warranted biopsy. The
      response to therapy was evaluated with social CT scans.

PMID- 14585565
TI  - Primary leptomeningeal lymphoma of the lumbar spine.
AB  - This report describes primary leptomeningeal lymphoma (PLML) of the spine in a 58
      year-old female. LML is rare, especially in the immunocompetent, and it is almost
      always secondary in origin. To our knowledge, there have been very few cases of
      PLML of the lumbar spine reported in the literature and even fewer reports using
      recent MR imaging (MRI) technology to aid with diagnosis. MRI is useful in
      differentiating CNS lesions and may be helpful in the diagnosis of this extremely
      rare primary lymphoma. PLML is briefly reviewed.

PMID- 14585566
TI  - Intraductal papillary carcinoma of bilateral breasts: a case report.
AB  - We report a 59-year-old woman presenting with a 2-month history of occasional
      bloody discharge from her right nipple and a palpable right breast mass on self
      examination. The mammography revealed heterogeneously dense fibroglandular
      stromas of bilateral breasts, a lobulated mass in her right breast associated
      with faint pleomorphic microcalcifications, and, in addition, very faint focal
      granular microcalcifications in the left breast. Breast ultrasound revealed a
      lobulated and heterogeneous hypoechoic tumor with irregular margins at the right
      breast and a well-circumscribed tumor with heterogeneous echotexture at the left
      breast.

PMID- 14585567
TI  - Chronic epigastric blood collection after coronary artery bypass grafting: case
      report.
AB  - A clinical case of epigastric pain 3 months after coronary artery bypass grafting
      (CABG) is presented. The CT finding of an abdominal mass with thick wall,
      internal horizontal by-gravity level and linear contrast enhancement at the
      border between the two different components was correctly interpreted for a
      chronic hematoma with separation of the formed blood elements from blood serum;
      in particular, the linear contrast enhancement was related to an artery-feeding
      vessel.

PMID- 14585569
TI  - Magnetic resonance imaging of an ileal carcinoid tumor. Correlation with CT and
      US.
AB  - The authors report the case of an advanced carcinoid tumor located in the distal
      ileum studied with CT, US and MRI. The lesion was deeply invasive and associated
      with liver metastases and peritoneal spreading. Imaging findings obtained with
      the different modalities have been reported, compared and discussed. MRI may play
      a role in the diagnosis and staging of carcinoid tumors, although CT still
      remains the investigation of choice.

PMID- 14585568
TI  - Computed tomographic image of an inflammatory fibroid polyp of the stomach.
AB  - Inflammatory fibroid polyp (IFP) is a rare benign lesion of the gastrointestinal
      tract. We report a case of IFP and its computed tomographic (CT) findings. On CT,
      the tumor protruded into the stomach and was covered with mucosa that was well
      enhanced. The inside of the tumor was irregularly enhanced, reflecting the
      typical histological findings of IFPs. Not only endoscopy and endoscopic
      ultrasonography (EUS) but also CT findings may be useful to diagnose IFP before
      polypectomy.

PMID- 14585570
TI  - Tuberculous pseudoaneurysm of gastroduodenal artery.
AB  - We report a patient with Gastroduodenal artery (GDA) pseudoaneurysm of
      tuberculous aetiology, who presented with massive hematemesis and who was
      successfully managed with transarterial steel coil embolization. Pseudoaneurysms
      are a rare but potentially fatal complication of tuberculosis and hence early
      recognition and management of this complication is important. To the best of our
      knowledge this is the first report of a GDA pseudoaneurysm resulting from
      tuberculosis.

PMID- 14585571
TI  - MRI findings of hepatic alveolar echinococcosis.
AB  - Diagnosis of liver infestation by alveolar echinococcosis (AE) is based on
      serologic, sonographic and computed tomography (CT) findings. Experience with
      magnetic resonance imaging (MRI) demonstrates that features of this disease are
      limited. CT and MRI findings of 14 cases with hepatic AE were compared in this
      report. We have described the MRI appearance of hepatic AE, which exhibits
      variable signal intensities on T1- and T2-weighted images. Fibrous and parasitic
      tissue showed low signal both on T1- and, generally, on T2-weighted images. In a
      few cases, a high signal on T2-weighted images may be observed, due either to
      central necrotic zones or to small peripheral cyst. MRI than by CT was more
      easily identified central necrosis. However, MRI seemed to be less effective than
      CT in allowing us to reach a positive diagnosis, due to its inability to show
      microcalcifications. In addition, MRI may not reveal small lesions. In most
      cases, T1-weighted images revealed more clearly than CT did the margins of the
      lesions and the hepatic extension, especially to hepatic veins, vena cava and
      perihepatic spaces.

PMID- 14585572
TI  - Percutaneous radiofrequency ablation of hepatocellular carcinoma in the presence
      of portal vein thrombosis.
AB  - Portal vein thrombosis (PVT) may not be an absolute contraindication for hepatic
      radiofrequency ablation (RFA). Although the data are sparse, PVT is commonly
      considered a contraindication to RFA. PVT has actually been described as a
      complication following RFA. RFA was used to treat a 3.9 x 2.9 cm primary
      hepatocellular carcinoma (HCC) in a patient with concomitant PVT without
      complication. RFA can be safely performed in this setting but further studies
      could clarify this issue.

PMID- 14585573
TI  - Radiology-Pathology Conference: Xanthogranulomatous cholecystitis.
AB  - We report the radiology and pathology of a patient with xanthogranulomatous
      cholecystitis (XC) and review the literature on this unusual condition.

PMID- 14585574
TI  - Adrenocortical oncocytoma: case report.
AB  - We report the case of an adrenocortical oncocytoma of the left adrenal cortex in
      a young woman. Physical examination revealed a mass in the left upper quadrant of
      the abdomen using abdomen ultrasound, computed tomography (CT) and magnetic
      resonance imaging (MRI), which allowed the identification of a large and
      inhomogeneous mass between the left kidney and the spleen. The lesion was not
      endowed of any specific radiologic characteristic nor bysided by any biochemical
      activity that could allow a radiological presurgical diagnosis. Surgical
      resection led to the diagnosis of adrenocortical oncocytoma, with no aspects
      revealing malignant potential.

PMID- 14585575
TI  - Castleman's disease.
AB  - We present a case of retroperitoneal Castleman's disease of the hyaline vascular
      type, with unusual MR imaging findings, differing form reports to date, along
      with a review of the imaging findings in Castleman's disease.

PMID- 14585576
TI  - Parosteal lipoma of the rib. CT findings and pathologic correlation.
AB  - Parosteal lipoma is a rare benign tumor composed of adipose tissue contiguous to
      the periosteum of the underlying bone. These tumors are slow-growing, nontender
      masses that affect, almost exclusively, the diaphysis of the long bones of the
      upper and lower limbs. We hereby describe the CT characteristics with the
      correlative pathological findings in a rare case of parosteal lipoma of the rib.

PMID- 14585594
TI  - Dynamic presynaptic varicosities: a role in activity-dependent synaptogenesis.
AB  - Recent developments in confocal imaging techniques have opened new avenues for
      investigating how synaptic networks evolve over time. These studies have revealed
      not only that synaptic structures are motile but also, most importantly, that a
      fraction of synapses undergo a continuous elimination and formation process, and
      that these mechanisms are markedly enhanced by activity. Turnover of dendritic
      spines was recently demonstrated in the somatosensory cortex upon sensory
      stimulation. De Paola et al. have now provided evidence for correlated
      remodelling of presynaptic structures. These results, together with others,
      indicate that activation of neuronal networks enhances dynamic mechanisms at both
      the presynaptic and the postsynaptic level, resulting in an increased turnover of
      synapses and, accordingly, a reorganization of synaptic circuitry.

PMID- 14585595
TI  - Hot and cold in Drosophila larvae.
AB  - Temperature is one of our most important physical cues, with extremes eliciting
      painful sensory warnings of tissue damage. Two recent publications present
      findings in Drosophila that implicate different neural substrates for low- and
      high-temperature responses, as well as indicating that a transient receptor
      potential (TRP) channel family member, painless, plays a role in these responses.

PMID- 14585596
TI  - Neuromelanin of the substantia nigra: a neuronal black hole with protective and
      toxic characteristics.
AB  - Neuromelanin accumulates in dopaminergic neurons during normal aging, and in
      Parkinson's disease, neurons with this pigment are those that selectively
      degenerate. Intraneuronal neuromelanin could play a protective role during its
      synthesis by preventing the toxic accumulation of cytosolic catechol derivatives
      and, in addition, by its ability to scavenge reactive metals, pesticides and
      other toxins to form stable adducts. However, dying neurons in Parkinson's
      disease that release neuromelanin might induce a vicious cycle of chronic
      neuroinflammation and neuronal loss.

PMID- 14585597
TI  - Paradoxical activities: insight into the relationship of parietal and prefrontal
      cortices.
AB  - What are the functions of the parietal and prefrontal cortices and how do these
      regions interact to achieve their objectives? How does context change plans for
      action? Are 'visual' and 'motor' well-defined attributes of neuronal activity in
      the association cortex? Recent studies of the saccadic system in monkeys have
      revealed two sets of paradoxical data: in parietal cortex, activity has visual
      timing but motor direction; in prefrontal cortex, activity has motor timing but
      visual direction. Analyzing the prefrontal and parietal data together leads to
      surprising insights. It appears that these paradoxical activities are
      intermediates in a parietal-prefrontal-parietal loop that has a rapid turnaround,
      and that a possibly prefrontal context-contingent signal switches sensorimotor
      transformations in parietal cortex.

PMID- 14585598
TI  - Glia as neural progenitor cells.
AB  - Recent studies have substantially expanded our conception of the roles for glia
      in function and maintenance of the adult nervous system. Of these reports,
      several have re-examined the lineage relationships among neural stem cells, their
      early radial glial derivatives and their mitotically competent neurogenic
      daughters. These studies have highlighted the role of radial cells in
      development, and of their glial progeny postnatally, as both progenitors and
      regulators of neuronal production and phenotype. In the adult mammalian brain,
      radial cell populations are scant, but their glial derivatives participate in a
      gliovascular network that organizes not only the structural and functional
      architecture of the brain but also its generative niches for resident progenitors
      - glial as well as neuronal. As in other organs, these progenitors can reside as
      transit-amplifying pools, by which lineage-biased progenitors expand to replenish
      discrete mature phenotypes. This review will consider the types of transit
      amplifying progenitor cells persistent in the adult mammalian CNS, and the extent
      to which these derive from glial phenotypes. It will also discuss the
      interactions of progenitor cells with their brethren that could specify their
      phenotype and fate, while defining the permissive niches for cell genesis in the
      adult CNS.

PMID- 14585599
TI  - New roles for astrocytes: the nightlife of an 'astrocyte'. La vida loca!
AB  - Like a newly popular nightspot, the biology of adult stem cells has emerged from
      obscurity to become one of the most lively new disciplines of the decade. The
      neurosciences have not escaped this trendy pastime and, from amid the noise and
      excitement, the astrocyte emerges as a beguiling companion to the adult neural
      stem cell. A once receding partner to neurons and oligodendrocytes, the astrocyte
      even takes on an alter ego of the stem cell itself (S. Goldman, this issue of
      TINS). Putting ego aside, the 'astrocyte' is also (and perhaps more importantly)
      an integral component of neural progenitor hotspots, where the craziness or 'la
      vida loca' of the nightlife might not be so wild when compared with our
      traditional understanding of the astrocyte. Here, astrocytes contribute to the
      instructive confluence of location, atmosphere and cellular neighbors that define
      the daily 'vida local' or everyday local life of an adult stem cell. This review
      discusses astrocytes as influential components in the local stem cell niche.

PMID- 14585600
TI  - 'Neuro'-peptides in glia: focus on NPY and galanin.
AB  - The term neuropeptide was advanced by de Wied and collaborators in the early
      seventies. At that time, they defined neuropeptides as endogenous substances
      synthesized in nerve cells and involved in nervous system functions. Since then,
      several studies have revealed that the very same 'neuropeptides' are also
      expressed in non-neuronal cells. It is therefore generally accepted that the
      original definition of these peptides was too limited and, consequently, it has
      recently been revised. Among the non-neuronal cells that synthesize neuropeptides
      are several glial cell types.

PMID- 14585602
TI  - Making connections: cholinesterase-domain proteins in the CNS.
AB  - Recent studies have highlighted novel functions of a group of cell adhesion
      molecules during nervous system development. Members of this protein family are
      characterized by an extracellular domain with sequence homology to
      cholinesterases and include the neuroligins, synaptic cell adhesion molecules
      recently implicated in autism, and neurotactin, a cell surface receptor involved
      in axonal pathfinding. Although these proteins have a structural organization
      similar to the enzyme acetylcholinesterase, the cholinesterase domain lacks
      enzymatic activity and functions as a protein-protein interaction motif. This
      protein family provides a striking example of how the function of a catalytically
      active domain has evolved to mediate receptor-ligand interactions that regulate
      morphogenetic processes during development of the nervous system.

PMID- 14585601
TI  - New roles for astrocytes: gap junction hemichannels have something to
      communicate.
AB  - Gap junctions are clusters of aqueous channels that connect the cytoplasm of
      adjoining cells. Each cell contributes a hemichannel, or connexon, to each cell
      cell channel. The cell-cell channels are permeable to relatively large molecules,
      and it was thought that opening of hemichannels to the extracellular space would
      kill cells through loss of metabolites, collapse of ionic gradients and influx of
      Ca(2+). Recent findings indicate that specific non-junctional hemichannels do
      open under both physiological and pathological conditions, and that opening is
      functional or deleterious depending on the situation. Most of these studies
      utilized cells in tissue culture that expressed a specific gap junction protein,
      connexin 43. Several such examples are reviewed here, with a particular focus on
      astrocytes.

PMID- 14585604
TI  - Interneuron diversity series: containing the detonation--feedforward inhibition
      in the CA3 hippocampus.
AB  - Feedforward inhibitory circuits are involved both in the suppression of
      excitability and timing of action potential generation in principal cells. In the
      CA3 hippocampus, a single mossy fiber from a dentate gyrus granule cell forms
      giant boutons with multiple release sites, which are capable of detonating CA3
      principal cells. By contrast, mossy fiber terminals form a larger number of
      Lilliputian-sized synapses with few release sites onto local circuit
      interneurons, with distinct presynaptic and postsynaptic properties. This
      dichotomy between the two synapse types endows the circuit with exquisite control
      over pyramidal cell discharge. Under pathological conditions where feedforward
      inhibition is compromised, focal excitation is no longer contained, rendering the
      circuit susceptible to hyperexcitability.

PMID- 14585603
TI  - Tyrosine kinases, synaptic plasticity and memory: insights from vertebrates and
      invertebrates.
AB  - Tyrosine kinases were first characterized in terms of their function during
      development. Over the past decade, it has become clear that tyrosine
      phosphorylation also plays an important role in the adult mammalian nervous
      system. This article reviews three different families of tyrosine kinase
      signaling cascades: the Trk receptor tyrosine kinases, the Src family of non
      receptor tyrosine kinases and the Eph receptor tyrosine kinases. Each of these
      cascades has been implicated in both adult synaptic plasticity and memory
      formation. Evidence from invertebrate systems also demonstrates a role for
      tyrosine kinase signaling in the induction of long-term memory, suggesting that
      molecular mechanisms of memory formation are conserved across species.

PMID- 14585605
TI  - Mammalian melanism: natural selection in black and white.

PMID- 14585607
TI  - Conservation, relocation and duplication in genome evolution.

PMID- 14585606
TI  - Generating and modifying DiGeorge syndrome-like phenotypes in model organisms: is
      there a common genetic pathway?

PMID- 14585608
TI  - Effects of reunited diverged regulatory hierarchies in allopolyploids and species
      hybrids.

PMID- 14585609
TI  - DNA repeats lead to the accelerated loss of gene order in bacteria.

PMID- 14585610
TI  - Sequencing the Oxytricha trifallax macronuclear genome: a pilot project.

PMID- 14585611
TI  - Evidence for cystine clustering in thermophilic proteomes.

PMID- 14585612
TI  - Selfish DNA is maladaptive: evidence from the plant Red List.

PMID- 14585613
TI  - Genome scans and candidate gene approaches in the study of common diseases and
      variable drug responses.

PMID- 14585614
TI  - Coordinate variation in meiotic pachytene SC length and total crossover/chiasma
      frequency under conditions of constant DNA length.

PMID- 14585615
TI  - Histone lysine methylation: a signature for chromatin function.

PMID- 14585616
TI  - Complex controls: the role of alternative promoters in mammalian genomes.

PMID- 14585617
TI  - Fundamentals of cDNA microarray data analysis.
AB  - Microarray technology is a powerful approach for genomics research. The multi
      step, data-intensive nature of this technology has created an unprecedented
      informatics and analytical challenge. It is important to understand the crucial
      steps that can affect the outcome of the analysis. In this review, we provide an
      overview of the contemporary trend on various main analysis steps in the
      microarray data analysis process, which includes experimental design, data
      standardization, image acquisition and analysis, normalization, statistical
      significance inference, exploratory data analysis, class prediction and pathway
      analysis, as well as various considerations relevant to their implementation.

PMID- 14585618
TI  - Pharmacogenetics: potential for individualized drug therapy through genetics.

PMID- 14585619
TI  - Development of biobased products.
AB  - Research conducted over the past seven years by the biotechnology byproducts
      consortium (BBC) addresses its mission to investigate the opportunities to add
      value to agricultural products, byproducts and coproducts and to manage the
      wastewater arising from agribusinesses in an environmentally favorable way. Since
      a wide variety of research approaches have been taken, the results are collected
      in five topic groups: (1) bioremediation that includes anaerobic fermentations of
      wastes to produce methane and hydrogen, the genetics of methanogenesis and in
      situ remediation of contaminated aquifer systems, landfill leachates and
      industrial effluents; (2) land application of fermentation byproducts and their
      use in animal feeds; (3) biocatalytic studies of transformations of components of
      corn and soybean oils, peroxidases present in plant products, such as soybean
      hulls; (4) biochemical reactions for the production of de-icers from industrial
      water streams, biodiesel production from fats and greases, biodegradable plastics
      from polymerizable sugar derivatives, single cell foods derived from fungal
      growth on waste streams, and bacterial polysaccharides from Erwinia species; (5)
      separation and recovery of components by membrane technologies.

PMID- 14585620
TI  - Hydrolysis of animal manure lignocellulosics for reducing sugar production.
AB  - Converting animal manure into value-added products provides a potential
      alternative for treatment and disposal of such materials. Lignocellulosics are a
      major component of animal manure and represent an undeveloped bioresource. In
      this work, a process was developed for hydrolyzing manure lignocellulosics into
      fermentable sugars. When raw dairy manure was pre-treated with 3% sulfuric acid
      at 110 degrees C for 1 h, hemicellulose was completely degraded into mainly
      arabinose, galactose and xylose. The pretreated materials were then treated with
      cellulolytic enzymes, Celluclast-1.5L and Novozyme-188, to hydrolyze the
      cellulose. The optimal enzyme loadings were identified as 13 FPU cellulase/g
      substrate and 5 IU beta-glucosidase/g substrate. The optimal temperature and pH
      were determined to be 46 degrees C and 4.8, respectively. A substrate
      concentration of 50 g/l favored both glucose concentration (in hydrolysate) and
      glucose yield (based on per 100 g manure). It was also found that a reduced
      particle size of 590-mum resulted in a high glucose yield with further decreases
      in particle size not increasing the yield. For each particle size investigated,
      the addition of 2% tween-80 resulted in at least 20% improvement in glucose
      yield. The optimized hydrolysis process achieved a glucose yield of 11.32 g/100 g
      manure, which corresponded to about 40% cellulose conversion.

PMID- 14585621
TI  - Mixed acid fermentation of paper fines and industrial biosludge.
AB  - This paper uses countercurrent fermentation to anaerobically convert paper fines
      and industrial biosludge to carboxylate salts using a mixed culture of acid
      forming microorganisms. Using the MixAlco process, the carboxylate salts can be
      thermally converted to ketones and hydrogenated into mixed alcohol fuels.
      Continuum particle distribution modeling (CPDM) correlated batch fermentation
      data to countercurrent fermentation data, allowing the prediction of product
      concentrations and conversions over a wide range of solid loading rates and
      liquid residence times. For 80% paper/20% biosludge, the predicted product
      concentrations agreed with the data within 7.7%. The predicted conversion agreed
      with the actual conversion within 27.8%. By correcting for varying selectivity,
      the predicted conversion agreed with the actual conversions within 15.2%. For 40%
      paper/60% biosludge, the predicted product concentrations agreed with the data
      within 9.6%. The predicted conversion agreed with the actual conversion within
      28.3%. By correcting for varying selectivity, the predicted conversion agreed
      with the actual conversions within 15.4%. For both the 80/20 and 40/60 cases,
      CPDM predicts that 90% conversion is possible with a 20 g/l product
      concentration, 300 g/l substrate concentration, 16 day liquid residence time, and
      2.5 g/(ld) solids loading rate. Before proceeding to an industrial plant, these
      predictions must be verified in a pilot plant.

PMID- 14585622
TI  - Dynamics of water-soluble carbon substances and microbial populations during the
      composting of de-inking paper sludge.
AB  - Composting is an alternative method to dispose of de-inking paper sludge (DPS).
      Today, few studies have investigated the water-soluble carbon (WSC) substances as
      indicators of the decomposition process and the microbial changes taking place
      during the composting of DPS. Accordingly, the goal is to study their dynamics
      during the composting of DPS at three nitrogen levels, 0.6%, 0.7% or 0.9% total
      N, using mechanical turning. The changes in WSC substances, microbial biomass
      carbon (MBC) and, total and DPS microbial populations were monitored during 24
      weeks. Also, microorganisms were identified and tested for the production of
      selected enzymes. Regardless of N treatments, the dynamic of WSC substances
      indicated that cellulose and hemicellulose fractions of DPS fibers were mainly
      biodegraded during the first 8 weeks while the more resistant carbon (C)
      fractions were biodegraded thereafter. MBC also evolved regardless of N
      treatments but was correlated to WSC substances. Its high values decline mostly
      after 12 weeks indicating the exhaustion of this source of C energy for microbial
      growth and the stabilisation of DPS organic matter. The dynamic and identified
      microorganisms were comparable to those observed in other composting processes.
      However, the results pointed out that those mostly implicated in the hydrolysis
      of DPS fibers were the thermophilic actinomycetes and fungi and, by comparison to
      the 0.6% or 0.7% N treatment, they decreased in presence of the 0.9% N treatment.
      Most microorganisms were hemicellulolytic bacteria, while actinomycetes and fungi
      were capable of degrading a wide variety of substrates. Overall, dynamics of WSC
      substances and microbial populations indicated that during composting, DPS
      decomposition obey a two phase decay while, contrary to the lowest N treatment,
      the 0.9% N treatment has slowed down this process by harming the important
      microbial populations implicated in the degradation of DPS fibers.

PMID- 14585623
TI  - Decolorization of reactive azo dyes by Cunninghamella elegans UCP 542 under co
      metabolic conditions.
AB  - The inappropriate disposal of dyes in wastewater constitutes an environmental
      problem and can cause damage to the ecosystem. Alternative treatments have been
      reported that fungi are particularly effective in the decolorization of textile
      effluents. The decolorization of dyes with different molecular structures by
      Cunninghamella elegans was evaluated under several media conditions. The
      decolorization procedures consisted of adding 72 h of mycelium into the culture
      medium containing either orange or reactive black or reactive red or a mixture of
      these dyes in the presence or absence of sucrose and/or peptone. The
      decolorization profile was highly dependent upon the incubation time, the
      molecular structure of the dye and presence or absence of co-substrates. The
      presence of sucrose or both sucrose and peptone significantly increased the
      decolorization of the solutions, however, the presence of only the nitrogen
      source suppressed it. The ultraviolet spectra of the solutions before and after
      decolorization suggested the occurrence of biodegradation in addition to the
      biosorption of the dyes. All tested dyes, except for the reactive black, caused
      inhibition of respiration of Escherichia coli, which suggested that toxic
      metabolites were produced.

PMID- 14585624
TI  - Optimization of extracellular lipase production by Geotrichum sp. using factorial
      design.
AB  - Response surface methodology was employed to study the effects of carbon source
      (soy oil, olive oil and glucose) and nitrogen source concentrations (corn steep
      liquor and NH(4)NO(3)) on the lipase production by Geotrichum sp. The experiment
      included a 2(4) central composite rotatable design (CCRD) and four others 2(3)
      CCRD. According to the responses from the experimental designs, the effects of
      each variable were calculated and the interactions between them were determined.
      The response surface methodology was applied for the optimization of the nutrient
      concentrations in the culture medium for the enzyme production, at 30 degrees C.
      The optimum medium composition for lipase production by Geotrichum sp. was
      ammonium nitrate 2.1-2.5%, corn steep liquor 13-15% and soy oil 0.6% as carbon
      source, which lead to a lipase activity of about 20 U/ml. Using olive oil as
      carbon source, the optimum composition was ammonium nitrate 0.8-1%, corn steep
      liquor 13-15% and olive oil 0.6%, leading to an activity of 17 U/ml.

PMID- 14585625
TI  - Yield, mushroom size and time to production of Pleurotus cornucopiae (oyster
      mushroom) grown on switch grass substrate spawned and supplemented at various
      rates.
AB  - To find a cost effective alternative substrate, Pleurotus cornucopiae 608 (yellow
      basidiomata) was grown on: (1) chopped, pasteurized switch grass (Panicum
      virgatum, 99%) with 1% ground limestone and (2) a mixture of pasteurized
      cottonseed hulls (75% dry wt.), 24% chopped wheat straw, and 1% ground limestone
      (all ingredients wt./wt.). The substrates were spawned at various levels (2.5%,
      3.75% or 5% wet wt., crop I) and non-supplemented or supplemented with commercial
      delayed release nutrient (Campbell's S-41) at various levels (0%, 1.5%, 3%, 4.5%,
      6%, 7.5% and 9% dry wt., crop II). Maximum yield (weight of fresh mushrooms
      harvested at maturity) was obtained on cottonseed hull/wheat straw substrate at a
      3.75-5% spawn level and 6% S-41 supplement. On switch grass substrate, increasing
      spawn levels and supplement levels stimulated yields in a linear fashion.
      However, maximum yields were only 46% or less for those of similar treatments on
      cottonseed hull/wheat straw substrate. Yields were three times higher on switch
      grass that was harvested after the grass had senesced (winter; beige color)
      compared to material that was harvested when the grass was green (summer; time of
      flowering). Additional physical processing of the material, such as milling, may
      improve yield potential of this material.

PMID- 14585626
TI  - Production of oligosaccharides by autohydrolysis of brewery's spent grain.
AB  - Brewery's spent grain was treated with water in a process oriented towards the
      production of xylo-oligosaccharides (XOS). A wide range of temperatures and
      reaction times were tested and the effects of these operational variables on
      hemicellulose solubilization and reaction products were investigated. The maximal
      XOS yield (61% of the feedstock xylan) was obtained at 190 degrees C after 5 min
      of reaction. Several oligosaccharide mixtures with different molecular weight
      distributions were obtained depending on temperature and reaction time. Longer
      reaction times led to decreased oligosaccharide production and enhanced
      concentrations of monosaccharides, sugar decomposition products and acetic acid.
      With reaction times leading to the maximal yields of XOS, little decomposition
      into organic acids and aldehydes was found at all the temperatures assayed. From
      the composition of processed solids, it was calculated that 63-77% of the initial
      xylan was selectively solubilized in autohydrolysis treatments.

PMID- 14585627
TI  - Incorporation of brewery waste in supplementary feed and its impact on growth in
      some carps.
AB  - Brewery waste (brewer's grains) was used at four different levels (10%, 20%, 30%
      and 40% w/w) replacing rice bran in fish diet under a semi-intensive culture
      system and its impact on the growth of catla, Catla catla; rohu, Labeo rohita and
      mrigal, Cirrhina mrigala, was studied. Growth in terms of body weight gain was
      maximum in C. catla and L. rohita fed on a diet containing 30% brewery waste in
      the feed, whereas C. mrigala, fed on a diet containing brewery waste at the above
      mentioned levels showed poorer growth than the control. A better growth
      performance was attributed to better absorption and utilization ability.

PMID- 14585628
TI  - Reusing soy residue for the solid-state fermentation of Ganoderma lucidum.
AB  - Lingzhi has been a popular oriental medicine used to treat various human
      diseases. Soy residue from the waste of tofu manufacturing was used to culture
      Ganoderma lucidum in solid-state fermentation. The solid-state fermentation was
      conducted in three types of containers: test tube, 500-ml flask, and sterilize
      able polypropylene plastic bag. The highest rate of mycelial growth of 6 mm/day
      was observed in the medium of carbon/nitrogen (C/N) ratio of 80 using test tubes.
      However, a growth rate of 7.5 mm/day was found at the C/N ratio of 70-80 in the
      500-ml flasks. In the tests using plastic bags, the fruiting bodies were fully
      developed only for the C/N ratios of 70 and 80. The components of fruiting bodies
      obtained from different media were also analyzed and compared. The contents of
      ash, polysaccharides, and crude protein of fruiting bodies were found higher in
      the media of C/N ratio of 80.

PMID- 14585629
TI  - The statin wars: why AstraZeneca must retreat.

PMID- 14585630
TI  - Laser treatment of acne.

PMID- 14585631
TI  - DiGeorge's syndrome: a gene at last.

PMID- 14585632
TI  - Immunotherapy of cytomegalovirus infection after stem-cell transplantation: a new
      option?

PMID- 14585633
TI  - Myocarditis: the unexpected return of smallpox vaccine adverse events.

PMID- 14585634
TI  - Incapacitating chemical weapons: a year after the Moscow theatre siege.

PMID- 14585635
TI  - Pulsed-dye laser treatment for inflammatory acne vulgaris: randomised controlled
      trial.
AB  - BACKGROUND: Low-fluence (low irradiation energy density) pulsed-dye lasers (PDLs)
      have been used for atrophic acne scarring, and anecdotal experience suggests that
      long-term improvements in inflammatory acne can be seen after one PDL treatment.
      Our aim was to compare the efficacy and tolerability of such PDL treatment with
      sham treatment in patients with facial inflammatory acne in a double-blind,
      randomised controlled trial. METHODS: We recruited 41 adults with mild-to
      moderate facial inflammatory acne. We randomly assigned patients to PDL (n=31) or
      sham treatment (n=10). Treatment was given at baseline and patients were seen
      after 2, 4, 8, and 12 weeks. Assessors and participants were unaware of treatment
      allocations. Primary outcome measures were acne severity after 12 weeks and
      adverse events at any time. Secondary measures were change in lesion counts after
      12 weeks and change in acne severity with time. Analysis was by intention-to
      treat. FINDINGS: After 12 weeks, acne severity (measured by Leeds revised grading
      system) was reduced from 3.8 (SD 1.5) to 1.9 (1.5) in the PDL group and 3.6 (1.8)
      to 3.5 (1.9) in the sham group (p=0.007). Treatment was well tolerated. Total
      lesion counts fell by 53% (IQR 19 to 64) in PDL patients and 9% (-16 to 38) in
      controls (p=0.023), and inflammatory lesion counts reduced by 49% (30 to 75) in
      PDL patients and 10% (-8 to 49) in controls (p=0.024). The most rapid
      improvements were seen in the first 4 weeks after treatment. INTERPRETATION: PDL
      therapy improves inflammatory facial acne 12 weeks after one treatment with no
      serious adverse effects.

PMID- 14585636
TI  - Epidemiology and cause of severe acute respiratory syndrome (SARS) in Guangdong,
      People's Republic of China, in February, 2003.
AB  - BACKGROUND: An epidemic of severe acute respiratory syndrome (SARS) has been
      associated with an outbreak of atypical pneumonia originating in Guangdong
      Province, People's Republic of China. We aimed to identify the causative agent in
      the Guangdong outbreak and describe the emergence and spread of the disease
      within the province. METHODS: We analysed epidemiological information and
      collected serum and nasopharyngeal aspirates from patients with SARS in Guangdong
      in mid-February, 2003. We did virus isolation, serological tests, and molecular
      assays to identify the causative agent. FINDINGS: SARS had been circulating in
      other cities of Guangdong Province for about 2 months before causing a major
      outbreak in Guangzhou, the province's capital. A novel coronavirus, SARS
      coronavirus (CoV), was isolated from specimens from three patients with SARS.
      Viral antigens were also directly detected in nasopharyngeal aspirates from these
      patients. 48 of 55 (87%) patients had antibodies to SARS CoV in their
      convalescent sera. Genetic analysis showed that the SARS CoV isolates from
      Guangzhou shared the same origin with those in other countries, and had a
      phylogenetic pathway that matched the spread of SARS to the other parts of the
      world. INTERPRETATION: SARS CoV is the infectious agent responsible for the
      epidemic outbreak of SARS in Guangdong. The virus isolated from patients in
      Guangdong is the prototype of the SARS CoV in other regions and countries.

PMID- 14585637
TI  - Severe visual impairment and blindness in children in the UK.
AB  - BACKGROUND: Prevention of visual impairment and blindness in childhood is an
      international priority. However, many countries do not have contemporary
      information about incidence and causes, from which the scope and priorities for
      prevention and treatment can be identified. METHODS: In the UK, children aged
      younger than 16 years newly diagnosed with severe visual impairment or blindness
      (SVI/BL, WHO criteria) during 2000 were identified through national active
      surveillance schemes in ophthalmology and paediatrics. From these data, we
      calculated yearly age-group specific incidence and cumulative incidence. Causes
      were classified by the anatomical site or sites affected and by timing of the
      insult or insults and causal factors, where known. FINDINGS: Of 439 newly
      diagnosed children, 336 (77%) had additional non-ophthalmic disorders or
      impairments (SVI/BL plus). Total yearly incidence was highest in the first year
      of life, being 4.0 (95% CI 3.6-4.5) per 10000, with a cumulative incidence by 16
      years of age of 5.9 (5.3-6.5) per 10000. 10% (44) of all children died within 1
      year of diagnosis of blindness. Prenatal causal factors affected 61% (268) of
      children, with perinatal or neonatal and childhood factors each affecting 18%
      (77). Incidence and causes varied with presence of non-ophthalmic impairments or
      disorders, birthweight, and ethnic origin. At least 75% (331) of children had
      disorders that were neither potentially preventable nor treatable, with current
      knowledge. INTERPRETATION: Severe visual impairment and blindness in childhood in
      the UK is more common, occurs more frequently in the context of complex non
      ophthalmic impairments, and has greater associated mortality, than previously
      assumed. An increased rate in children of low birthweight and from ethnic
      minority groups, together with the observed diversity and complexity of the
      causes, reflect recent secular changes in the population at risk, specific risk
      factors, and strategies available for treatment.

PMID- 14585638
TI  - Role of TBX1 in human del22q11.2 syndrome.
AB  - BACKGROUND: Del22q11.2 syndrome is the most frequent known chromosomal
      microdeletion syndrome, with an incidence of 1 in 4000-5000 livebirths. It is
      characterised by a 3-Mb deletion on chromosome 22q11.2, cardiac abnormalities, T
      cell deficits, cleft palate facial anomalies, and hypocalcaemia. At least 30
      genes have been mapped to the deleted region. However, the association of these
      genes with the cause of this syndrome is not clearly understood. METHODS: To test
      for the chromosomal deletion at 22q11.2, we did fluorescence in-situ
      hybridisation analysis with ten probes on 22q11.2 in 235 unrelated patients with
      clinically diagnosed del22q11.2 syndrome. To investigate mutations in the coding
      sequence of TBX1, we also did genetic analysis in 13 patients from ten families
      who have the 22q11.2 syndrome phenotype but no detectable deletion of 22q11.2.
      FINDINGS: 96% (225 of 235) of patients had a defined 1.5-3-Mb deletion at
      22q11.2. We identified three mutations of TBX1 in two unrelated patients without
      the 22q11.2 deletion-one with sporadic conotruncal anomaly face
      syndrome/velocardiofacial syndrome and one with sporadic DiGeorge's syndrome-and
      in three patients from a family with conotruncal anomaly face
      syndrome/velocardiofacial syndrome. We did not record these three mutations in
      555 healthy controls (1110 chromosomes; p<0.0001). INTERPRETATION: Our results
      suggest that the TBX1 mutation is responsible for five major phenotypes in
      del22q11.2 syndrome. Therefore, we conclude that TBX1 is a major genetic
      determinant of the del22q11.2 syndrome.

PMID- 14585639
TI  - Heart failure in acute febrile neutrophilic dermatosis.

PMID- 14585640
TI  - Adoptive cellular therapy for early cytomegalovirus infection after allogeneic
      stem-cell transplantation with virus-specific T-cell lines.
AB  - Adoptive transfer of CMV-specific T cells offers the potential for reconstitution
      of viral immunity after allogeneic transplantation. However, the logistics of
      producing virus-specific T-cell clones has limited the application of cellular
      therapies. We treated 16 patients for CMV infection with polyclonal CMV-specific
      T-cell lines generated by short-term culture. Massive in-vivo expansions of CMV
      specific cytotoxic T lymphocytes were observed, resulting in reconstitution of
      viral immunity. In eight cases antiviral drugs were not required, and subsequent
      episodes of reactivation occurred in only two patients. Our findings indicate
      that application of CMV-specific cell lines is both feasible and effective in a
      clinical environment.

PMID- 14585641
TI  - Eosinophilic-lymphocytic myocarditis after smallpox vaccination.
AB  - Smallpox is an eradicated viral disease that has re-emerged as a potential
      bioterrorism threat. Smallpox vaccination was historically the most effective
      defence measure against wild smallpox virus. The risk of myopericarditis after
      vaccination might limit this option. We report a case of biopsy-proven
      eosinophilic-lymphocytic myocarditis diagnosed in vivo with histological evidence
      for eosinophil-mediated cardiac myocyte necrosis shortly after smallpox
      vaccination. Furthermore, we report a beneficial haemodynamic response to high
      dose corticosteroids. A better understanding of the aberrant immune mechanism of
      myocyte injury after smallpox vaccination might improve the risk/benefit
      assessment for people considering smallpox vaccination and better smallpox
      vaccines in the future.

PMID- 14585642
TI  - Rickets.
AB  - Rickets, once thought vanquished, is reappearing. In some less developed
      countries it hardly went away. This seminar reviews the effects of genes, stage
      of development, and environment on clinical expression of the disease. Rickets
      can be secondary to disorders of the gut, pancreas, liver, kidney, or metabolism;
      however, it is mostly due to nutrient deficiency and we concentrate on this form.
      Although calcium deficiency contributes in communities where little cows' milk is
      consumed, deficiency of vitamin D is the main cause. There are three major
      problems: the promotion of exclusive breastfeeding for long periods without
      vitamin D supplementation, particularly for babies whose mothers are vitamin D
      deficient; reduced opportunities for production of the vitamin in the skin
      because of female modesty and fear of skin cancer; and the high prevalence of
      rickets in immigrant groups in more temperate regions. A safety net of extra
      dietary vitamin D should be re-emphasised, not only for children but also for
      pregnant women. The reason why many immigrant children in temperate zones have
      vitamin D deficiency is unclear. We speculate that in addition to differences in
      genetic factors, sun exposure, and skin pigmentation, iron deficiency may affect
      vitamin D handling in the skin or gut or its intermediary metabolism.

PMID- 14585643
TI  - Small RNA: can RNA interference be exploited for therapy?
AB  - CONTEXT: RNA interference (RNAi) is the sequence-specific gene-silencing induced
      by double-stranded RNA (dsRNA), and gives information about gene function
      quickly, easily, and inexpensively. The use of RNAi for genetic-based therapies
      is widely studied, especially in viral infections, cancers, and inherited genetic
      disorders. RNAi has been used to make tissue-specific knockdown mice for studying
      gene function in a whole animal. Combined with genomics data, RNAi-directed gene
      silencing could allow functional determination of any gene expressed in a cell or
      pathway. The term RNAi came from the discovery that the injection of dsRNAs into
      Caenorhabditis elegans interferes with the expression of specific genes
      containing a complementary region to the delivered dsRNA. Although stalled for a
      time by the non-gene-specific interferon response elicited by dsRNA molecules
      longer than about 30 nucleotides in mammalian cells, Tom Tuschl's group found
      that transfection of synthetic 21-nucleotide small-interfering RNA (siRNA)
      duplexes were highly selective and sequence-specific inhibitors of endogenous
      genes. STARTING POINT: siRNA expression has been studied with siRNA from plasmid
      and viral vectors that efficiently deliver siRNAs into both dividing and non
      dividing cells, stem cells, zygotes, and their differentiated progeny. A
      collection of RNA interference vectors that suppress 50 human de-ubiquitinating
      enzymes allowed Thijn Brummelkamp and colleagues to study this gene family and to
      identify de-ubiquitinating enzymes in cancer-relevant pathways (Nature 2003; 424:
      797-801). These researchers found that the familial cylindromatosis tumour
      suppressor gene (CYLD), previously of unknown function, could enhance the
      activation of the transcription factor NF-kappaB, leading to increased resistance
      to apoptosis. They have now started to investigate the use of CYLD inhibitors in
      clinical trials. WHERE NEXT: The ability to efficiently and stably produce and
      deliver sufficient amounts of siRNA to the proper target tissues require
      refinement before this new technology can be tried clinically. Initial in-vivo
      studies reported effective transgene suppression in adult mice by chemically
      synthesised siRNAs. More recently many researchers have used plasmid and viral
      vectors for transcription of short-hairpin RNAs, both in vitro and in vivo. With
      these expression systems, gene expression was more stably inhibited than with the
      transient knockdown recorded with chemically synthesised siRNA. Human trials
      exploiting these latest findings are likely to soon follow.

PMID- 14585645
TI  - Tackling socioeconomic inequalities in health: analysis of European experiences.
AB  - Effective strategies must be developed to reduce socioeconomic inequalities in
      health. Most efforts take place in isolation, and only the UK experience has been
      discussed widely in international published work. We therefore analysed policy
      developments on health inequalities in different European countries between 1990
      and 2001. We noted that countries are in widely different phases of awareness of,
      and willingness to take action on, inequalities in health. We identified
      innovative approaches in five main areas: policy steering mechanisms; labour
      market and working conditions; consumption and health-related behaviour; health
      care; and territorial approaches. National advisory committees in the UK, the
      Netherlands, and Sweden have proposed comprehensive strategies to reduce health
      inequalities. Variations between these packages suggest that policymaking in this
      area still is largely intuitive and would benefit from incorporation of more
      rigorous evidence-based approaches. Further international exchanges of
      experiences with development, implementation, and evaluation of policies and
      interventions to reduce health inequalities can help to enhance learning speed.

PMID- 14585644
TI  - Doctor performance and public accountability.
AB  - Public concern about the quality of health care has motivated governments, health
      care funders, and clinicians to expand efforts to improve professional
      performance. In this paper, we illustrate such efforts from the perspective of
      three countries, the UK, the USA, and the Netherlands. The earliest strategies,
      which included continuing professional education, clinical audits, and peer
      review, were aimed at the individual doctor, and produced only modest effects.
      Other efforts, such as national implementation of practice guidelines, effective
      use of information technologies, and intensive involvement by doctors in
      continuous quality-improvement activities, are aimed more broadly at health-care
      systems. Much is yet unknown about whether these or other strategies--such as
      centralised supervision or regulation of quality improvement, or use of financial
      incentives--are effective. As demands for greater public accountability rise,
      continuing performance improvement efforts of each of our countries offer us
      opportunities to learn from one another.

PMID- 14585646
TI  - European Clinical Trials Directive: responses made to MHRA consultation letter
      MLX 287.

PMID- 14585647
TI  - LIFE: losartan versus atenolol.

PMID- 14585648
TI  - LIFE: losartan versus atenolol.

PMID- 14585649
TI  - Myocardial dysfunction: hibernation and remodelling.

PMID- 14585650
TI  - Drug therapy and microvolt T-wave alternans testing.

PMID- 14585653
TI  - Coeliac disease.

PMID- 14585655
TI  - Ethics and research in developing countries.

PMID- 14585656
TI  - End-of-life decisions and conflicts of interest.

PMID- 14585658
TI  - Health promotion approach for control of Taenia solium infection in Nepal.

PMID- 14585659
TI  - Prognosis of diabetes in the developing world.

PMID- 14585660
TI  - Clinical xenotransplantation.

PMID- 14585661
TI  - Clinical xenotransplantation.

PMID- 14585663
TI  - Social capital.

PMID- 14585665
TI  - Ruth Hart.

PMID- 14585664
TI  - Nicolae Paulesco: an international polemic.

PMID- 14585667
TI  - Discarded diagnoses Monomania.

PMID- 14585668
TI  - Claude Libert.

PMID- 14585669
TI  - Adventures in otology.

PMID- 14585670
TI  - Critical overview and outlook: pathogenesis, prevention, and treatment of
      hepatitis and hepatocarcinoma caused by hepatitis B virus.
AB  - Viral hepatitis B is an enigmatic disease in which the host's own immune response
      to persistent viral infection may bring about host destruction through antiviral
      inflammatory responses which might otherwise present as a benign or inapparent
      disease. The simple solution to the hepatitis B problem is by immunoprophylaxis
      using the vaccine licensed in 1981, which prevents both infection and the late
      sequelae of liver cirrhosis and hepatocarcinoma. Immunotherapeutic vaccines
      against persistent hepatitis B infection have not been successful and new
      explorations are being directed to therapies which include antisense, ribozymes,
      gene silencing by RNA interference (RNAi) and aptamer approaches. Limited
      benefits from nucleoside therapy and limitations in opportunity for liver
      transplantation have left a large void of curative treatments. Findings with
      respect to e antigen tolerance provide a basis for exploration to determine
      whether passively administered e antigen might suppress cell-mediated immunity,
      creating a commensal state in which virus persists but without pathologic damage
      to the host. Therapy of hepatocarcinoma by conventional chemotherapy, radiation,
      or surgical resection and ablation gives little hope for restoration of health
      unless the tumor is detected very early. The large engagement of the world
      medical science community to develop therapeutic vaccines against cancer is now
      in major clinical trials to determine the hope and credibility for the
      immunization approach. Vaccines based on tumor peptides which are linked to heat
      shock proteins and directed to host dendritic cells give reason for excitement
      and may be the "best show in town". A new era of tumor therapy will need to be
      based on new discoveries in immune function which are required to pursue
      immunotherapy on a more rational basis. The many facets of current hepatitis B
      virology, pathogenesis, immunoprophylaxis, immunotherapeusis, chemotherapy, and
      tumor pathogenesis and therapy are discussed here, in depth, but in keeping with
      needed brevity.

PMID- 14585671
TI  - A combined dual-chamber typhoid/hepatitis A vaccine as a booster dose in
      hepatitis A primed adults.
AB  - Vivaxim is a combined hepatitis A/typhoid fever vaccine (HA/Vi) licensed for
      vaccination of travellers, but long-term protection against hepatitis A requires
      two immunisations at least 6 months apart. A randomised, controlled study was
      performed in 116 healthy adults primed with hepatitis A vaccine (Avaxim) to
      compare immune responses to HA/Vi and Avaxim given as booster doses 6 months
      later. Both vaccines elicited marked booster responses achieving antibody
      geometric mean titres (GMTs) of 4576 and 3760 mIU/ml in the HA/Vi and Avaxim
      groups, respectively. Although twice as frequent in the HA/Vi group, local
      reactions (mostly pain) were mainly mild and transient, probably reflecting the
      larger volume injected (1ml). Vivaxim offers a convenient means of administering
      both HA and typhoid fever vaccines in subjects already primed for hepatitis A.

PMID- 14585672
TI  - Kinetics of the immune response after primary and booster immunization against
      tick-borne encephalitis (TBE) in adults using the rapid immunization schedule.
AB  - A total of 222 adult subjects aged 19-51 years were enrolled in this multi
      center, phase III study to evaluate immunogenicity and safety of the first
      booster immunization with a new tick-borne encephalitis (TBE) vaccine. This was
      an extension study that followed subjects who had received primary immunization
      12-18 months previously with either the new or formerly licensed TBE vaccine
      according to the rapid immunization schedule (i.e. on Days 0, 7 and 21). Compared
      to the levels of primary immunization, prior to first booster, neutralizing TBE
      antibodies (geometric mean titers, GMTs) of both vaccination groups had remained
      on a high level and were far above the detection limit of the neutralization test
      used. All subjects showed a sharp increase of TBE antibodies following the
      booster. The booster was well tolerated by the subjects. CONCLUSION: These
      results in terms of both immunogenicity and safety indicate that the TBE
      vaccination with this new TBE vaccine can be used effectively and safely in
      adults. A long lasting immunity can be concluded from the strong immune response
      following the first booster.

PMID- 14585673
TI  - A DNA vaccine directed against a rainbow trout rhabdovirus induces early
      protection against a nodavirus challenge in turbot.
AB  - A DNA vaccine encoding the envelope glycoprotein from a fish rhabdovirus, viral
      hemorrhagic septicemia virus (VHSV), has previously been shown to induce both
      early and long time protection against the virus in rainbow trout. Challenge
      experiments have revealed that the immunity established shortly after vaccination
      is cross-protective against heterologous fish rhabdoviruses. In this study, we
      show that the DNA vaccine encoding the VHSV glycoprotein also induces early
      protection against a non-enveloped, positive-sense RNA virus belonging to the
      Nodavirus family, the Atlantic halibut nodavirus (AHNV). In a vaccine efficacy
      test using juvenile turbot as model fish, the fish injected with the VHSV vaccine
      were completely protected against a nodavirus challenge performed 8 days post
      vaccination, while the cumulative mortality in the control group reached 54%. A
      DNA vaccine carrying the gene encoding the capsid protein of AHNV revealed no
      protective properties against the nodavirus challenge. Histological examination
      of muscle tissue sections from the vaccine injection site showed that the DNA
      vaccine against VHSV triggered a pronounced inflammatory response in turbot
      similar to what has earlier been observed in rainbow trout.

PMID- 14585674
TI  - Immunotherapy against murine experimental visceral leishmaniasis with the FML
      vaccine.
AB  - The fucose mannose ligand (Leishmania donovani FML)-saponin vaccine has earlier
      shown its immunoprophylactic potential against visceral leishmaniasis in the CB
      hamster (87.7% of parasite load reduction), Balb/c (84.4%) and Swiss albino mouse
      (85-93%) models. In this investigation its specific immunotherapeutic efficacy
      against L. donovani infection in Balb/c mice was studied. The effects of vaccine
      treatment on the humoral response, delayed type of hypersensitivity to
      promastigote lysate (DTH), cytokine levels in sera and reduction of the liver
      parasitic load of L. donovani infected mice, were examined. The types and
      subtypes of anti-FML antibodies increased significantly in the vaccinees over the
      saline and saponin controls. As expected for a saponin vaccine, the highest
      ratios were found in relation to IgG1, IgG2a and IgG2b (4.4, 5 and 2.5,
      respectively). The DTH response and the in vitro ganglion cell proliferative
      response against FML antigen were also significantly higher than controls
      (P<0.005). Concomitantly, an impressive and specific decrease of liver parasitic
      burden was detected only in vaccine-treated animals (94.7%). Our results indicate
      that the therapeutic FML-vaccine has a potent effect on modulation of the murine
      infection leading to the reduction of parasitic load and signs of disease, being
      a new potential tool in the therapy and control of visceral leishmaniasis.

PMID- 14585675
TI  - Efficient vaccine against the virus causing a lethal disease in cultured Cyprinus
      carpio.
AB  - We have isolated a virus, which causes a mortal disease in cultured ornamental
      Koi and Common carps (Cyprinus carpio) in many countries worldwide. This
      unclassified virus, which causes nephritis and gill necrosis, and so has been
      given the name carp nephritis and gill necrosis virus (CNGV), has a morphology
      resembling the herpes virus, but bears a genomic DNA of ca 250-300 kbp. So far,
      both others and we have been unable to find CNGV-DNA sequences possessing a
      significant similarity to known DNA viruses. The virus induces a lethal disease
      when water temperature ranges between 18 and 25 degrees C (permissive
      temperature). In this report, we demonstrate that carps, exposed to the virus at
      23 degrees C for 3-5 days and then transferred to the non-permissive temperature
      of 30 degrees C, became resistant to a challenged infection and their sera
      demonstrated a high level of virus-specific antibodies. We have isolated
      attenuated non-pathogenic viruses that render virus-vaccinated carps resistant to
      the disease. Furthermore, vaccinated fish developed high levels of antibodies
      against the virus. We suggest, therefore, that this attenuated virus could be
      used as a live vaccine for the eradication of the mortal disease afflicting
      Common and ornamental carp fisheries in many countries.

PMID- 14585676
TI  - Reduced experimental autoimmune encephalomyelitis after intranasal and oral
      administration of recombinant lactobacilli expressing myelin antigens.
AB  - Oral administration of autoantigens is a safe and convenient way to induce
      peripheral T-cell tolerance in autoimmune diseases like multiple sclerosis (MS).
      To increase the efficacy of oral tolerance induction and obviate the need for
      large-scale purification of human myelin proteins, we use genetically modified
      lactobacilli expressing myelin antigens. A panel of recombinant lactobacilli was
      constructed producing myelin proteins and peptides, including human and guinea
      pig myelin basic protein (MBP) and proteolipid protein peptide 139-151 (PLP(139
      151)). In this study we examined whether these Lactobacillus recombinants are
      able to induce oral and intranasal tolerance in an animal model for multiple
      sclerosis, experimental autoimmune encephalomyelitis (EAE). Lewis rats received
      soluble cell extracts of Lactobacillus transformants intranasally three times
      prior to induction of EAE. For the induction of oral tolerance, rats were fed
      live transformed lactobacilli for 20 days. Ten days after the first oral
      administration EAE was induced. Intranasal administration of extracts containing
      guinea pig MBP (gpMBP) or MBP(72-85) significantly inhibited EAE in Lewis rats.
      Extracts of control transformants did not reduce EAE. Live lactobacilli
      expressing guinea pig MBP(72-85) fused to the marker enzyme beta-glucuronidase
      (beta-gluc) were also able to significantly reduce disease when administered
      orally. In conclusion, these experiments provide proof of principle that
      lactobacilli expressing myelin antigens reduce EAE after mucosal (intranasal and
      oral) administration. This novel method of mucosal tolerance induction by mucosal
      administration of recombinant lactobacilli expressing relevant autoantigens could
      find applications in autoimmune disease in general, such as multiple sclerosis,
      rheumatoid arthritis and uveitis.

PMID- 14585677
TI  - v-src oncogene-specific carboxy-terminal peptide is immunoprotective against Rous
      sarcoma growth in chickens with MHC class I allele B-F12.
AB  - B(12) haplotype of the inbred chicken line CB (B12/B12) contains, like the bulk
      of chicken MHC(B) haplotypes, only a single dominantly expressed class I molecule
      (B-F). The peptide binding motifs for this major B-F12 molecule in chickens of
      Rous sarcoma regressor line CB (B12/B12) have been determined. Using stringent
      and relaxed motifs, several peptides were found in the v-src molecule of the PR
      RSV-C, but most of these peptides are identical with that of endogenous c-src.
      Only the v-src C-tail peptide(517-524) (LPACVLEV) contains critical anchor amino
      acids (valine at positions 5 and 8) and shows a sequence different from the
      corresponding c-src peptide. This v-src C-tail peptide up-regulates expression of
      the B-F12 class I molecule on PBL, as assessed by FACS analysis, and stimulates T
      cell proliferation in a [3H]thymidine uptake assay. A protective effect of the
      immune response to LPACVLEV against RSV challenge was demonstrated in CB
      (B12/B12) chickens immunised with peptides encapsulated in liposomes.

PMID- 14585678
TI  - Public opponents of vaccination: a case study.
AB  - Opposition to mass childhood vaccination is a world-wide phenomenon, particularly
      in industrialised countries. Unfounded claims about vaccination are perpetuated
      by parental lobby groups and individual spokespeople, some of whom have a medical
      or scientific background. This article focuses on one such spokesperson who has
      achieved particular notoriety. Dr. Viera Scheibner is a retired
      micropalaeontologist, without any formal training in health-related sciences, who
      tours the world claiming that vaccines are ineffective and dangerous and lead to
      a host of ills such as cancer and asthma. Professionals in public health or the
      clinical arena are from time to time called upon to publicly respond to her, or
      similar, claims disseminated during tours of Europe, North America or Australasia
      and in books and articles. Health professionals have expressed at how such
      spokespersons misrepresent the evidence on vaccine safety, resulting in the
      potential to undermine public confidence in immunisation. Media coverage, or
      proposed coverage, particularly of her more extreme claims, often makes health
      professionals engaged in immunisation feel obliged to respond. This paper
      describes Viera Scheibner's approach, which follows a repetitious path and is
      representative of that taken by other public opponents of immunisation. We
      conclude by suggesting how health professionals might respond in the public
      arena.

PMID- 14585680
TI  - Possibility of application of new pneumococcal conjugate vaccines in children in
      Slovenia.
AB  - The emergence of pneumococcal strains resistant to penicillin caused a lot of
      problems in the therapy of invasive diseases, and added new dimensions to the
      role of immunisation. In addition to the currently available 23-valent
      pneumococcal polysaccharide vaccine (PPV) and a new 7-valent conjugate vaccine
      (PCV) (Prevnar, Wyeth Lederle), two new conjugate vaccines-a 9- and a 11-valent
      are being developed. So far, the choice of most appropriate vaccines has depended
      on the established prevalence of serotypes causing invasive diseases and their
      antibiotic resistance in the Slovene children population. Between 1993 and 2001,
      263 invasive pneumococcal strains isolated from children with invasive diseases
      were typed. During the period 1998-2001, the same 161 invasive strains were
      tested for their antibiotic sensitivity. Streptococcus pneumoniae was identified
      as the major cause of invasive bacterial diseases in the Slovene children
      population, especially in children under 4 years of age. Distribution by age
      groups showed the highest incidence in children aged 0-1 years. The predominant
      serotypes in all age groups were serotypes 14, 1, 19F, 23F, 6B, 18C and 6A. The
      distribution of penicillin-intermediate and penicillin-resistant strains showed
      the predominance of serotypes 23F, 14 and 19F. As concerns infection with S.
      pneumoniae serotypes, we have proved that children aged less than 5 years are
      more likely to be infected with penicillin-nonsusceptible or intermediate
      susceptible strains than older children. The 7-valent conjugate vaccine covers
      74% of invasive strains in toddlers, but is less effective in older children. We
      can conclude that the 9-valent vaccine formulation is optimal for our country,
      but further cost-effectiveness analysis must be done for recommendation of wide
      use. At that moment it is reasonable to use the 7-valent conjugate vaccine for
      children with chronic cardiovascular, pulmonary, urinary and liver diseases, with
      asplenia, neoplasmia, diabetes, meningomyelocoele, before or after bone marrow
      transplantation and in cases of immunodeficiency.

PMID- 14585679
TI  - Immune response in mice inoculated with plasmid DNAs containing multiple-epitopes
      of foot-and-mouth disease virus.
AB  - This paper focuses on the development of candidate DNA vaccine encoding antigenic
      epitopes of type O foot-and-mouth disease virus (FMDV). A series of plasmids
      encoding different combinations of B cell epitopes and a T cell epitope were
      constructed and characterized by inoculating BALB/c mice. The specific antibodies
      were only detectable in the mice inoculated with plasmids encoding the T cell
      epitope and B cell epitopes from sites 5 and 1, within which site 5 includes
      residues 135-167 of VP1 and site 1 includes 141-160 region (G-H loop) and
      carboxyl terminus of VP1. Stronger cellular immune responses were also observed
      in these mice using T cell proliferation assay.

PMID- 14585682
TI  - Role of L-lysine HCl in immunopotentiation towards development of suitable
      tuberculosis vaccination.
AB  - L-Lysine HCl is being proposed to be a possible biocompatible adjuvant to enhance
      immune response by virtue of its probable non-specific bridging action and
      cellular proliferation properties. This proposal has been tried to be
      substantiated by carrying out experimentation where L-lysine HCl has been used as
      an adjuvant (various groups based on mode of application and frequency of booster
      dose were designed) in tuberculosis vaccination experiments with heat killed
      Mycobacterium tuberculosis (MTB) and Bacille Calmette Guerin (BCG). Antibody
      titre has been followed in all the experiments as a measure of immune response.
      Amongst the various groups designed, group 1A (L-lysine HCl was given at a
      separate site as that of the antigen; lysine booster was given to this group
      intermittently, i.e. lysine given on 0th, 7th, 14th, 21st days of immunization)
      came out as the stand-alone leader. This mode and frequency of application was
      then compared with a group which received a standard adjuvant, viz. alhydrogel.
      Results were obtained which showed the following order in terms of decreasing
      antibody titre: alhydrogel group > lysine group > control group. Considering the
      biocompatible nature of lysine in comparison with the reportedly hazardous nature
      of alum adjuvants, we propose L-lysine HCl as a probable adjuvant in vaccination.

PMID- 14585681
TI  - Cholera vaccine candidate 638: intranasal immunogenicity and expression of a
      foreign antigen from the pulmonary pathogen Coccidioides immitis.
AB  - Vibrio cholerae strain 638 is a live genetically attenuated candidate cholera
      vaccine in which the CTXPhi prophage encoding cholera toxin has been deleted and
      hapA, encoding an extracellular Zn-dependent metalloprotease, was insertionally
      inactivated. Strain 638 was highly immunogenic when inoculated to adult Swiss
      mice by the intranasal route as judged by the induction of a strong serum
      vibriocidal antibody response. A side-by-side comparison of strain 638 with its
      isogenic hapA(+) precursor (strain 81) in the above model indicated that
      inactivation of hapA does not affect immunogenicity. The spherule-associated
      antigen 2/proline-rich antigen (Ag2/PRA) of Coccidioides immitis has been shown
      to protect mice against coccidioidomycosis to an extent dependent on the modes of
      antigen presentation and challenge with C. immitis arthrospores. In this work, we
      demonstrate the use of a live genetically attenuated V. cholerae strain to
      deliver Ag2/PRA. Ag2/PRA was expressed in 638 as a fusion protein with the
      Escherichia coli heat labile toxin B subunit leader peptide using the strong Tac
      promoter. The recombinant Ag2/PRA was efficiently expressed, processed and
      secreted to the periplasmic space. Intranasal immunizations of adult mice with
      strain 638 expressing Ag2/PRA induced serum vibriocidal antibody response to the
      vector strain and serum total IgG response to Ag2/PRA. Strain 638 expressing PRA
      could be recovered from trachea and lung up to 20h after immunization but was
      effectively cleared 72h post-inoculation.

PMID- 14585683
TI  - Comparative efficacy of various chemical stabilizers on the thermostability of a
      live-attenuated peste des petits ruminants (PPR) vaccine.
AB  - Thermostability of a live-attenuated peste des petits ruminants (PPR) vaccine
      recently developed at Indian Veterinary Research Institute was studied using
      conventional lyophilization conditions. A total of four stabilizers viz.,
      lactalbumin hydrolysate-sucrose (LS), Weybridge medium (WBM), buffered gelatin
      sorbitol (BUGS) and trehalose dihydrate (TD) were used to prepare the lyophilized
      vaccine. The study revealed that the PPR vaccine lyophilized with either LS or TD
      is more stable than rest of the stabilizers having an expiry period of at least
      45 days (so far studied) at 4 degrees C, 15-19 days at 25 degrees C and 1-2 days
      at 37 degrees C. However, at a temperature of 45 degrees C, BUGS had a marginal
      superiority, although lasted for few hours, followed by TD and LS with respect to
      shelf-life, LS and TD with respect to half-life. On the basis of half-life also
      LS followed by TD appeared superior at a temperature of 4, 25 and 37 degrees C.
      Reconstitution of vaccine with distilled water or 1M MgSO(4) or 0.85% NaCl
      maintained the required virus titre (2.5log(10)TCID(50) per dose) up to 8h at 37
      degrees C and 7h at 45 degrees C. Among the three diluents, 1M MgSO(4) appeared
      to be the better diluent for reconstitution of lyophilized PPR vaccine, as the
      loss on dilution was lowest and maintain the required virus titre for a longer
      period. Investigation suggests for using LS as stabilizer for lyophilization and
      1M MgSO(4) as vaccine diluent for the newly developed PPR vaccine.

PMID- 14585684
TI  - Development and large-scale use of recombinant VP2 vaccine for the prevention of
      infectious bursal disease of chickens.
AB  - Infectious bursal disease virus (IBDV) is the causative agent of Gumboro disease,
      an infectious disease of global economic importance in poultry. One of the most
      effective types of inactivated IBDV vaccine is produced by infecting young
      chickens with a virulent strain, sacrificing them and extracting the virus from
      the bursa of Fabricius. The goal of this study was to produce an effective
      subunit vaccine against IBDV thereby providing an effective means of combating
      the disease. In areas in which the bursa-derived vaccine is in use, this subunit
      vaccine would eliminate the use of live birds for the production of inactivated
      vaccines. The gene for viral protein 2 (VP2) of IBDV was cloned into a Pichia
      pastoris expression system. This efficient system allowed us to meet the need for
      inexpensive vaccines required by the poultry industry. Following expression and
      scale-up, the protein was used to vaccinate chickens, against either Gumboro
      disease alone or in combination with inactivated Newcastle disease virus (NDV).
      Full protection was conferred against IBDV following vaccination with the subunit
      recombinant vaccine. No untoward influence on the response to the NDV vaccine was
      recorded. Over 250 million birds have already been vaccinated with this vaccine.
      The advantages of a subunit vaccine over an inactivated one are discussed. This
      approach will enable rapid adjustment to new virulent strains if and when they
      appear.

PMID- 14585685
TI  - Sulfation of silk fibroin by chlorosulfonic acid and the anticoagulant activity.
AB  - Silk fibroin (Bombyx mori) was sulfated using chlorosulfonic acid in pyridine. FT
      IR spectra showed introduction of sulfate group by this reaction; NMR spectra
      indicated that sulfation occurred mainly at tyrosine and serine residues.
      Molecular size decreased and dispersed with sulfation. The molecular weight was
      estimated in around 20,000 by GPC using protein standards. Amino acid composition
      suggested that sulfated fibroin came from H-chain of fibroin; the crystal region
      of fibroin molecule remained in sulfated fibroin. The amount of sulfate groups
      increased with overall reaction time. The maximum amount was estimated in 1.0
      mmol/g by acidimetric titration. Sulfation efficiency was calculated as 66.7%.
      Blood coagulation was prevented by 0.5 mg of sulfated fibroin in 1 ml of blood,
      while original fibroin did not show any effect. Anticoagulant activity of
      sulfated fibroin strongly depends on the amount of sulfate groups introduced.
      These results indicate that sulfate group introduction results in addition of
      anticoagulant function to silk fibroin. Sulfated fibroin is a new type of
      anticoagulant material having a protein backbone.

PMID- 14585686
TI  - Biocompatibility of micro- and nano-particles in the colon. Part II.
AB  - Pathological colonic tissues were investigated with an Environmental Scanning
      Electron Microscope technique to verify the presence of inorganic, non
      biodegradable pollutants, i.e. micro- and nano-debris of exogenous origin, after
      debris in liver and kidney had been discovered. In all, 18 samples of colon
      tissues affected by cancer and Crohn's disease were evaluated and found in all
      the cases to contain micro- and nano-particles. Their chemistry, detected with an
      X-ray microprobe, indicated a heterogeneous nature, whereas the size of the
      particles was homogeneous. Three control samples of healthy, young, cadavers were
      analysed and showed the absence of debris within the normal, healthy colon
      mucosa. The study reveals the presence of particulate debris, generally
      considered as biocompatible, in pathological specimens of human colon. The
      findings suggest a possible link between the presence of such particles and the
      underlying pathology in the cases analysed.

PMID- 14585687
TI  - Magnesia-doped HA/beta-TCP ceramics and evaluation of their biocompatibility.
AB  - The sintering behavior, mechanical properties and biocompatibility of magnesia
      (MgO)-doped HA/TCP biphasic ceramics were studied. Pure HA/TCP ceramics showed
      poor sinterability due to the phase transformation of beta- to alpha-TCP. MgO
      doped HA/TCP ceramics showed high density without any phase transformation of
      beta-TCP up to 1300 degrees C, for MgO dopants incorporated into the beta-TCP
      preferably and increased thermal stability of beta-TCP. However, the addition of
      MgO higher than a critical content, suppressed grain growth of HA/TCP ceramics
      and lowered sinterability. The optimum amount of MgO doping was 1 wt%, which lead
      99% relative density and higher mechanical properties than HA or beta-TCP
      ceramics. From in vitro test and in vivo test, 1 wt% MgO-doped HA/TCP ceramics
      showed a good biocompatibility without cytotoxicity. After implantation under the
      muscle of rabbits, beta-TCP phase was dissolved from the surface and a biological
      apatite covered the surface. These results proved that MgO addition increased
      drastically the sintering and mechanical properties of HA/beta-TCP ceramics
      without altering the biological safety and biocompatibility of the original
      composite.

PMID- 14585688
TI  - Nanotexturing of titanium-based surfaces upregulates expression of bone
      sialoprotein and osteopontin by cultured osteogenic cells.
AB  - Bone formation around implants is influenced by surface geometry. Since
      cell/matrix/substrate interactions associated with cell signaling occur in the
      nanoscale dimension, we have evaluated the influence of nanotexturing of titanium
      based surfaces on the expression of matrix proteins by cultured osteogenic cells
      at initial time points. Cells were obtained by enzymatic digestion of newborn rat
      calvaria and grown on titanium and titanium alloy discs with nanotextured or
      machined surfaces, and on glass coverslips for periods of 6 h, 1 day, and 3 days,
      under standard culture conditions. Cultures were processed for single or dual
      immunolabeling with monoclonal and/or polyclonal antibodies against bone
      sialoprotein (BSP), fibronectin (FN), osteopontin (OPN), type-I pro-collagen, or
      tubulin, followed by corresponding fluorophore-conjugated secondary antibodies.
      Some samples were processed for scanning electron microscope analysis of
      morphology and immunogold labeling. After 6 h, nanotextured surfaces exhibited up
      to a nine-fold increase in the proportion of cells with peripheral OPN labeling.
      At day 3, the proportion of OPN and BSP labeled cells was higher, and the
      intensity of immunoreactivity dramatically increased. No significant differences
      were observed in the expression pattern and the proportion of cells
      immunoreactive for FN or type-I pro-collagen. Our results demonstrate that
      nanotexturing of titanium-based surfaces upregulates the early expression of BSP
      and OPN in osteogenic cell cultures.

PMID- 14585689
TI  - In vivo evaluation of plasma sprayed hydroxyapatite coatings having different
      crystallinity.
AB  - In this paper, hydroxyapatite (HA) coatings having the crystallinities of 56% and
      98% were deposited by the plasma spraying and vapor-flame treatment process. The
      phase composition and crystallinity of the coatings were investigated by X-ray
      diffraction and infrared spectra. The dissolution behavior of the coatings in
      tris-buffer solutions was examined. The results obtained indicated that the
      coating having the high crystallinity showed the lower dissolution as compared to
      the low crystallinity coating. The bone bonding ability of HA coatings were
      observed in vivo by implanted in dog's femur. After 3 months implantation, the
      high crystallinity coating showed the higher shear strengths and remained
      integrated, whereas the separation of the coating fragments was clearly observed
      in the coating having low crystallinity.

PMID- 14585690
TI  - Endothelium regeneration on luminal surface of polyurethane vascular scaffold
      modified with diamine and covalently grafted with gelatin.
AB  - Using the recently developed surface modification technique, free amino groups
      have been introduced onto polyester-type polyurethane (PU) scaffolds. The
      introduction of these free amino groups increases the surface energy and provides
      a convenient way to further immobilize bioactive species such as gelatin,
      collagen or chitosan, etc. on the scaffold surface by employing glutaraldehyde as
      a coupling agent. These modifications are advantageous to enhance cell-material
      interaction. The culture of human umbilical vein endothelial cells (HUVECs) in
      vitro proved that the cell proliferation ratio of both the aminolyzed and the
      biomacromolecules-immobilized PU membranes was improved greatly comparing with
      the control PU. Scanning electron microscopy and confocal laser scanning
      microscopy observations displayed that the gelatin-immobilized PU vascular
      scaffold had formed a monolayer of endothelial intima on its luminal surface
      after HUVECs were cultured for 6 d. Therefore, the aminolysis and the following
      biomacromolecule immobilization is a promising way to enhance the cell-PU
      interaction that can accelerate the endothelium regeneration, which is crucial
      for blood vessel tissue engineering.

PMID- 14585691
TI  - A histological evaluation on self-setting alpha-tricalcium phosphate applied in
      the rat bone cavity.
AB  - This study aimed to elucidate the biological effects of a self-setting tricalcium
      phosphate bone substitute (BIOPEX) applied in rat femoral cortical bone cavities.
      Narrow penetrations through the cavity and bone marrow were prepared to obtain
      cellular sources. In the experimental group at day 1, a thin cell layer intruded
      into a narrow space between the grafted BIOPEX and the bottom of the cavity. From
      days 5 to 10, a range of tartrate-resistant acid phosphatase (TRAPase)-reactive
      osteoclasts accumulated on the surface of the BIOPEX facing the bottom of the
      cavity, whilst many alkaline phosphatase (ALPase)-positive osteoblasts were
      localized on the bone surface opposing the BIOPEX. However, at day 20,
      osteoblasts were localized neighboring the osteoclasts on the BIOPEX, and
      deposited bone matrices onto this material, implying a coupling between
      osteoclasts and osteoblasts. At days 30 and 40 post-operation, small remnants of
      BIOPEX particles were present in the new bone with a profile of compact bone.
      Thus, BIOPEX is resorbed by osteoclasts, and succeeded by osteoblastic bone
      apposition with a coupling of osteoclasts and osteoblasts at the later stage. In
      conclusion, the use of BIOPEX provides adequate bone regeneration with the
      profile of compact bone.

PMID- 14585692
TI  - Osteoinduction of porous bioactive titanium metal.
AB  - This is the first report of bone induction in a non-osseous site by titanium
      metal, which has long been recognized as a non-bioactive material. After
      undergoing specific chemical and thermal treatments, porous bioactive titanium
      induced bone formation without the need of additional osteogenic cells or
      osteoinductive agents. Four types of titanium implants were implanted in the
      dorsal muscles of mature beagle dogs, and were examined histologically after
      periods of 3 and 12 months. Chemically and thermally treated titanium, as well as
      pure titanium, was implanted either as porous blocks or as fibre mesh cylinders.
      Bone formation was found only in the chemically and thermally treated porous
      block implants removed after 12 months. The present study shows that even a non
      soluble metal that contains no calcium or phosphorus can be an osteoinductive
      material when treated to form an appropriate macrostructure and microstructure.
      This finding may elucidate the nature of osteoinduction, and lead to the advent
      of epochal osteoinductive biomaterials for tissue regeneration.

PMID- 14585693
TI  - Novel micro-crosslinked poly(organophosphazenes) with improved mechanical
      properties and controllable degradation rate as potential biodegradable matrix.
AB  - As biodegradable materials, linear polyphosphazenes undergo rapid hydrolysis
      degradation but exhibit poor mechanical properties. Blending with biodegradable
      polyesters or inorganic particles strengthen their mechanical properties but give
      rise to slower degradation rate. To balance the mechanical properties and the
      degradation rate, micro-crosslinked polyphosphazenes were synthesized in this
      study. Their glass transition temperatures, mechanical properties, and in vitro
      degradation behavior were investigated. 2-hydroxyethyl methacrylate (HEMA) was
      firstly attached to the side chain along with glycine ethyl ester to prepare co
      substituted poly(organophosphazene) with pendant ethenyl substituents. The co
      substituted poly(organophosphazene) was blended with HEMA or acrylic acid (AA)
      followed by a free radical polymerization to prepare micro-crosslinked
      poly(organophosphazenes). The resulting crosslinked polymers showed two separate
      glass transition temperatures depending on the HEMA or AA feed. Incorporation of
      crosslinking affected the mechanical properties positively. Crosslinked
      poly(organophosphazenes) showed an approximately 11-17 fold increase in terms of
      modulus of elasticity when compared to the linear counterpart. In vitro
      degradation tests indicated that HEMA-crosslinked polymers hydrolyzed at a
      retarded rate while AA-crosslinked polymers hydrolyzed at a moderate rate
      compared to linear polymers.

PMID- 14585695
TI  - Identification of fibroin-derived peptides enhancing the proliferation of
      cultured human skin fibroblasts.
AB  - We previously reported that the fibroin of the silkworm Bombyx mori enhanced the
      proliferation of cultured human skin fibroblasts. In this work, the fibroin was
      digested by chymotrypsin, and the resulting peptide fragments were fractionated
      and assayed for their biological activity. Two peptides that promoted fibroblast
      growth were isolated and identified to be VITTDSDGNE and NINDFDED. Both sequences
      are found in the N-terminal region of the fibroin polypeptide and are thought to
      be the active principle of fibroblast growth-promoting activity.

PMID- 14585694
TI  - Gravity spinning of polycaprolactone fibres for applications in tissue
      engineering.
AB  - Poly(epsilon-caprolactone) (PCL) fibres have been produced by wet spinning from
      solutions in acetone under low shear (gravity flow) conditions. The tensile
      strength and stiffness of as-spun fibres were highly dependent on the
      concentration of the spinning solution. Use of a 6% w/v solution resulted in
      fibres having strength and stiffness of 1.8 MPa and 0.01 GPa, respectively,
      whereas these values increased to 9.9 MPa and 0.1 GPa when fibres were produced
      from 20% w/v solutions. Cold drawing to an extension of 500% resulted in further
      increases in fibre strength (up to 50 MPa) and stiffness (0.3 GPa). The surface
      morphology of as-spun fibres was modified, to yield a directional grooved pattern
      by drying in contact with a mandrel having a machined topography characterised by
      a peak-peak separation of 91 microm and a peak height of 30 microm. Limited in
      vitro studies of cell behaviour in contact with the fibres were performed using
      cell culture. The number of attached fibroblasts and myoblasts on as-spun PCL
      fibres after 5 days in cell culture was lower than on tissue culture plastic by a
      factor 2 and 1.5, respectively, but higher than on Dacron monofilament by a
      factor of 4 and 11, respectively. The high fibre compliance and the potential for
      controlling the fibre surface architecture to promote contact guidance effects
      together with the maintained proliferation of fibroblasts and myoblasts on as
      spun PCL fibres in vitro recommends their use for 3-D scaffold production in soft
      tissue engineering.

PMID- 14585696
TI  - Degradation of a collagen-chondroitin-6-sulfate matrix by collagenase and by
      chondroitinase.
AB  - Highly porous, type I collagen-chondroitin-6-sulfate (collagen-GAG) scaffolds,
      produced by freeze-drying techniques, have proven to be of value as implants to
      facilitate the regeneration of certain tissues. The objective of this project was
      to evaluate changes in the microstructure and mechanical properties of selected
      collagen-GAG scaffolds as they degrade in an in vitro model system. Environmental
      scanning electron microscopy and video imaging demonstrated that collagenase
      degradation caused strut erosion through the creation of 1-3 microm diameter
      micropits within a 2-h period, leading to eventual removal of strut material and
      strut breakage. Loss of microstructural topography may have been due to
      gelatinization when collagen was cleaved by collagenase. Chondroitinase
      degradation of GAG resulted in swelling of the struts, causing the pores to
      become smaller and rounder. The compressive modulus of the collagen-GAG matrix
      decreased when degraded by collagenase, but remained unchanged when degraded by
      chondroitinase. Carbodiimide-cross-linked matrices were found to have a higher
      cross-link density, a higher compressive stiffness and a greater resistance to
      collagenase and chondroitinase, compared to non-cross-linked controls and
      matrices that were cross-linked by the dehydrothermal process. This investigation
      provides information that can be used to design collagen-GAG scaffolds with
      desired compressive stiffness and degradation rate to collagenase and
      chondroitinase.

PMID- 14585697
TI  - A hyaluronan-based nerve guide: in vitro cytotoxicity, subcutaneous tissue
      reactions, and degradation in the rat.
AB  - We investigated possible cytotoxic effects, biocompatibility, and degradation of
      a hyaluronan-based conduit for peripheral nerve repair. We subjected the conduits
      to an in vitro fibroblast cytotoxicity test and concluded that the conduits were
      not cytotoxic. Subsequently, we implanted the conduits subcutaneously in rats, in
      order to investigate tissue reactions and biodegradation. Initially, a fibrin
      matrix was formed around the material, while the surroundings were relatively
      quiet. Macrophages (MO) migrated to the conduits and formed giant cells next to
      the material after 5 days. The maximum presence of MO was found after 3-6 weeks.
      The appearance of MHC class II cells showed a similar pattern. Highest numbers of
      giants reached a maximum after 6-12 weeks. Angiogenesis was started in the
      surroundings of the hyaluronan-based conduit within a few days. Massive ingrowth
      of blood vessels into the biomaterial was found after 6 weeks as well as cellular
      ingrowth into the lumen of the tube. At that time the tubular structure of the
      conduit was lost and loose biomaterial fibers were observed. The results show
      that a hyaluronan-based conduit is not cytotoxic and shows good biocompatibility.
      Such a conduit may be suitable as a guide in peripheral nerve repair.

PMID- 14585698
TI  - Phosphate glasses for tissue engineering: Part 1. Processing and characterisation
      of a ternary-based P2O5-CaO-Na2O glass system.
AB  - This paper presents the results of a study of the thermal properties, X-ray
      powder diffraction (XRPD), NMR and solubility of a range of phosphate-based
      glasses. Ion release and pH measurements were also obtained. The compositions
      were limited by fixing the P2O5 mol% content at 45, 50 and 55 mol%, and varying
      the CaO mol% at 30, 35 and 40 mol%. Initial data collected from thermal analysis
      showed an increase in the Tg values, with increasing CaO mol%, as expected. An
      increase in crystallisation temperatures with increasing CaO mol% was also
      observed, with sharp peaks indicating the presence of single and/or double
      phases. Initial XRPD data revealed that the 45 mol% P2O5 precipitated a calcium
      bridged trimetaphosphate (Na4Ca[PO3]6) at the sodium oxide contents of 25 and 20
      mol%, but at the 15 mol% level two phases formed, NaCa[PO3]3 and Ca2P2O7. The 50
      mol% P2O5 compositions showed two sodium phosphate-rich phases [NaCa(PO3)3 and
      NaPO3] for the lower calcium containing compositions, and a calcium phosphate
      phase [CaP2O6] for compositions with higher CaO mol%. The 55 mol% P2O5
      compositions, exhibited similar phases for the lower calcium containing
      compositions, and a single calcium phosphate phase (CaP2O6) was identified for
      the higher calcium containing composition. NMR analysis revealed the presence of
      Q1 and Q2 species in the 45 mol% P2O5 compositions, and Q2 species present in the
      50 and 55 mol% P2O5 compositions. The non-linear data obtained from the thermal
      and solubility analyses conducted were attributed to the packing density of the
      45 mol% P2O5 compositions. The solubility was seen to decrease with increasing
      CaO mol%, for all the glasses investigated, and all the compositions showed a
      gradual decrease in pH with time, and this was accounted for by the release of
      Na+ and Ca2+ ions into solution.

PMID- 14585699
TI  - Phosphate glasses for tissue engineering: Part 2. Processing and characterisation
      of a ternary-based P2O5-CaO-Na2O glass fibre system.
AB  - This paper presents the results of a study of the thermal properties, solubility
      and dimensions of a range of phosphate-based glass fibres (PB-GFs). The glass
      compositions were limited by fixing the P2O5 content to 45, 50 and 55 mol%, and
      varying the CaO mol% at 30, 35 and 40. PB-GFs were obtained from the 50 and 55
      mol% P2O5 compositions; however, we were unable to obtain fibres from the 45 mol%
      compositions. This was linked to the cross-linked density, network connectivity
      and average chain length of the compositions studied. With regards to thermal
      parameters investigated, initial data showed an increase of the Tg and
      crystallisation temperatures with increasing CaO mol% at each fixed phosphate
      content. A decrease in Tg temperatures was also observed with increasing P2O5
      content to 55 mol%. The crystallisation temperatures obtained for compositions
      with fixed phosphate at 55 mol%, showed a reverse pattern, with a decrease in
      values as compared to the fixed 50 mol% phosphate compositions. The diameters of
      the fibres all decreased with increasing RPMs as expected, and the solubility
      also increased with increasing RPMs. This was related to the increased surface
      area of the higher RPM fibres. There was also a decrease seen in solubility with
      increasing CaO mol%.

PMID- 14585700
TI  - Effect of bilobalide on peripheral nerve regeneration.
AB  - The present study provides in vivo trials of silicone rubber chambers filled with
      different concentrations of bilobalide (0, 50, 100, 200, 400 microM) to bridge a
      15 mm sciatic nerve defect in rats. Collagen was also filled in the chambers to
      prevent the bilobalide from leakage. Histological and electrophysiological
      techniques were used to evaluate the functional recovery of the nerve. At the
      conclusion of 8 weeks, animals from the group treated with the bilobalide,
      especially at the concentration of 200 microM, had a higher rate (40%) of
      successful regeneration across the wide gap and a significantly larger number of
      myelinated axons (4094 +/- 1555), compared to only 10% and 2485 in the control
      group. However, the high dose bilobalide (400 microM) completely reversed this
      positive effect of growth-promoting capability and inhibited nerve regeneration.
      Only 10% of the animals treated with the high dose bilobalide had regenerated
      cables within the silicone rubber chambers. These results indicated that
      bilobalide could be involved in both positive and negative effects on
      regenerating nerves. Therefore, whether a proper dosage of bilobalide is used or
      not plays a critical factor in deciding if it can sustain nerve regeneration over
      long gaps.

PMID- 14585701
TI  - Improved biocompatibility of small intestinal submucosa (SIS) following
      conditioning by human endothelial cells.
AB  - Small intestinal submucosa (SIS) is a naturally occurring tissue matrix composed
      of extracellular matrix proteins and various growth factors. SIS is derived from
      the porcine jejunum and functions as a remodeling scaffold for tissue repair.
      While SIS has proven to be a useful biomaterial for implants in vivo, problems
      associated with endothelialization and thrombogenicity of SIS implants may limit
      its vascular utility. The goal of this study was to determine if the biological
      properties of SIS could be improved by growing human umbilical vein endothelial
      cells (HUVEC) on SIS and allowing these cells to deposit human basement membrane
      proteins on the porcine substrate to create what we have called "conditioned" SIS
      (c-SIS). Using an approach in which HUVEC were grown for 2 weeks on SIS and then
      removed via a technique that leaves behind an intact basement membrane, we
      hypothesized that the surface properties of SIS might be improved. We found that
      when re-seeded on c-SIS, HUVEC exhibited enhanced organization of cell junctions
      and had increased metabolic activity compared to cells on native SIS (n-SIS).
      Furthermore, HUVEC grown on c-SIS released lower amounts of the pro-inflammatory
      prostaglandin PGI2 into the media compared to cells grown on n-SIS. Additionally,
      we found that adhesion of resting or activated human platelets to c-SIS was
      significantly decreased compared to n-SIS suggesting that, in addition to
      improved cell growth characteristics, conditioning SIS with human basement
      membrane proteins might decrease its thrombogenic potential. In summary,
      conditioning of porcine SIS by human endothelial cells improves key biological
      properties of the material that may improve its usefulness as remodeling scaffold
      for tissue repair. Identification of critical modifications of SIS by human
      endothelial cells should help guide future efforts to develop more biocompatible
      vascular grafts.

PMID- 14585702
TI  - In vitro study of osteogenic differentiation of bone marrow stromal cells on heat
      treated porcine trabecular bone blocks.
AB  - This in vitro study investigated the potential of the heat-treated porcine
      trabecular bone block as a bone substitute for the treatment of bone defects or
      related diseases. Chemical, mechanical, and morphological studies of bone blocks
      were performed. The resultant properties were compared with the properties of
      currently available commercial products from bovine trabecular bones. The major
      component of the bone block was hydroxyapatite, and the ratio of Ca/P was 1.65
      1.66. The average values of the compressive Young's modulus and the ultimate
      strength were 346.33 +/- 83.15 and 6.66 +/- 1.62 MPa, respectively. The pore size
      of the heat-treated bone blocks was approximately 300-500 microm. For the
      biological investigations, expanded bone marrow stromal cells (BMSCs) were
      isolated from the femurs of New Zealand White rabbits and were dynamically seeded
      into the heat-treated porcine bone block (10x10x5 mm3). Before the cells were
      seeded, the heat-treated porcine bone blocks were divided into two groups:
      collagen coated blocks (n=16) and uncoated blocks (n=16). Within each group, the
      blocks were again divided into two groups, depending on the culture method, i.e.,
      static or rotating culture. Cells were cultured in the blocks for up to 6 weeks.
      Scanning electron microscopic examination after 4 weeks showed that the cell
      layers attached to the porcine bone block. Proliferation and osteogenic
      differentiation were analyzed by cell counting, an MTT assay, alkaline
      phosphatase activity, and total protein content. The deposition of extracellular
      substances and osteoid formation surrounded by osteoblast-like cuboidal cells
      were confirmed through histochemical staining and transmission electron
      microscopy. Based on the results of this study, we conclude that heat-treated
      porcine trabecular bone has great potential as a bone substitute and may even be
      superior to currently available commercial products.

PMID- 14585704
TI  - Backgrounds of antibiotic-loaded bone cement and prosthesis-related infection.
AB  - Antibiotic-loaded bone cement has been in use for over 30 years for the fixation
      of total joint arthroplasties, although its mechanism of action is still poorly
      understood. This review presents the backgrounds of bone cements, prosthesis
      related infection and antibiotic-loaded bone cements. It is shown that antibiotic
      loaded bone cement has a significant effect on bacteria, particularly in animal
      and clinical studies. However, recently, antimicrobial resistance among bacteria
      has been ascribed to the antibiotic-loaded bone cement. The unresolved issues
      both regarding the action of antibiotic-loaded bone cement and the nature of the
      antimicrobial resistance necessitate further research into the interaction of
      antibiotic-loaded bone cement and bacteria.

PMID- 14585703
TI  - Characters of dendritic poly(L-lysine) analogues with the terminal lysines
      replaced with arginines and histidines as gene carriers in vitro.
AB  - The development of a non-viral gene delivery system into cells is an important
      key to realize the safe delivery of therapeutic genes without the side effects
      often pointed out for viral vectors. We have shown that dendritic poly(L-lysine)
      of the 6th generation (KG6) shows high transfection efficiency into several
      cultivated cells with low cytotoxicity. Here, to investigate the effect of
      substituting terminal cationic groups on the gene delivery into cells, we
      synthesized KGR6 and KGH6, in which terminal amino acids were replaced by
      arginines and histidines, respectively. DNA-binding analysis showed that KGR6
      could bind to the plasmid DNA as strongly as KG6, whereas KGH6 showed decreased
      binding ability. KGR6 showed 3- to 12-fold higher transfection efficiency into
      several cultivated cells than KG6. In contrast, KGH6 showed no transfection
      efficiency. However, once KGH6 was mixed with the DNA under acidic conditions (pH
      5.0), DNA-complexes were formed and they showed high transfection efficiency
      compared to that in KG6-mediated transfection. DNA-complexes of KGH6 formed under
      acidic conditions were 1-2 microm and spherical, and relatively stable under
      neutral conditions. The size and spherical shape of the complexes were the same
      as those of KG6. The unique character of KGH6 will be one of the basic and
      valuable tools which will enable us to construct a functional gene transfection
      system in vitro and in vivo.

PMID- 14585705
TI  - A simple soft lithographic route to fabrication of poly(ethylene glycol)
      microstructures for protein and cell patterning.
AB  - We present a simple, direct soft lithographic method to fabricate poly(ethylene
      glycol) (PEG) microstructures for protein and cell patterning. This lithographic
      method involves a molding process in which a uniform PEG film is molded with a
      patterned polydimethylsiloxane stamp by means of capillary force. The patterned
      surfaces created by this method provide excellent resistance towards non-specific
      protein and cell adsorption. The patterned substrates consist of two regions: the
      molded PEG surface that acts as a resistant layer and the exposed substrate
      surface that promotes protein or cell adsorption. A notable finding here is that
      the substrate surface can be directly exposed during the molding process due to
      the ability to control the wetting properties of the polymer on the stamp, which
      is a key factor to patterning proteins and cells.

PMID- 14585706
TI  - Structural characterization of nano-sized calcium deficient apatite powders.
AB  - Nano-sized calcium-deficient apatitic (CDHA) crystals with Ca/P ratios from 1.5
      to 1.67 were synthesized using wet chemical method and of needle-like shape with
      5-10 nm in diameter and 40-50 nm in length was observed. The structural
      environment of the Ca atoms in all the CDHA nano-crystals has been investigated
      using EXAFS, XANES and EELS. The results reveal that a maximum Fourier transform
      amplitude occurs at the apatite with a Ca/P ratio of 1.67 and the structural
      disorder increase following the sequence of 1.67>1.5>1.6>1.55. A similar
      phenomenon is also observed in both K-edge XANES and L(2,3)-edge ELNES in the Ca
      atom. The structural analysis further demonstrates that different chemical and
      biological properties among these CDHA nano-crystals with Ca/P ratio from 1.5 to
      1.67 are primarily due to the effect of stoichiometry and non-stoichiometry as
      compared to the structural order-disorder.

PMID- 14585707
TI  - Immobilization of Candida rugosa lipase on chitosan with activation of the
      hydroxyl groups.
AB  - A method for immobilization of Candida rugosa lipase to two types of chitosan
      beads by activating the hydroxyl groups of chitosan using carbodiimide coupling
      agent has been successfully developed. The ability of carbodiimide to activate
      the hydroxyl groups of chitosan was confirmed using the electron spectroscopy for
      chemical analysis (ESCA) technique. The properties of lipase immobilized using
      dry and wet chitosan beads were also investigated and compared. Immobilization
      enhanced the enzyme stability against changes of pH and temperature. High storage
      stability of 30 days and an increased enzyme activity of 2,110% were observed in
      wet immobilized lipase. Immobilized lipase using dry and wet chitosan beads
      retained 78% and 85% of its initial activity after 10 batch hydrolytic cycles.
      The kinetic parameters Km and Vmax were determined for the free and immobilized
      lipase. The activation energy (Ea) was found to decrease for immobilization of
      lipase on chitosan beads.

PMID- 14585708
TI  - Synthesis of methacryloyloxyethyl phosphate copolymers and in vitro calcification
      capacity.
AB  - Methacryloyloxyethyl phosphate is a methacrylic monomer used to modify different
      substrates by copolymerisation, in order to enhance hydroxyapatite deposition
      onto their surfaces. We report the synthesis of two copolymers series using
      increasing concentrations of methacryloyloxyethyl phosphate with (diethylamino)
      ethyl methacrylate and 1-vinyl-2-pyrrolidinone. Reactivity ratios were evaluated
      for the two copolymer systems. The influence of phosphate content and
      distribution on the capacity to form a calcium-rich layer was evaluated after
      immersion for 15 days in a synthetic body fluid. Corresponding homopolymers were
      synthesised as controls. Calcium-phosphorus globules were developed only on
      samples containing (diethylamino) ethyl methacrylate, and presenting a low
      density of phosphate groups. The amounts of calcium increased when higher
      concentrations of methacryloyloxyethyl phosphate were used. The use of 1-vinyl-2
      pyrrolidinone was associated with greater calcium amounts, (compared to
      (diethylamino) ethyl methacrylate). The amine groups may favour the attraction of
      phosphorus, thus creating another way for the nucleation of calcium/phosphate
      crystals.

PMID- 14585709
TI  - Zirconium oxide: analysis of MG63 osteoblast-like cell response by means of a
      microarray technology.
AB  - Zirconium oxide ceramics have outstanding mechanical properties, a high
      biocompatibility and a high resistance to scratching. Expression profiling by DNA
      microarray is a molecular technology that allows the analysis of gene expression
      in a cell system. By using DNA microarrays containing 19,200 genes, we identified
      in osteoblast-like cells line (MG-63) cultured on zirconium oxide discs (Cercon,
      Degussa Dental, Hanau, Germany) several genes whose expression was significantly
      up or down-regulated. The differentially expressed genes cover a broad range of
      functional activities: (a) immunity, (b) vesicular transport and (c) cell cycle
      regulation. It was also possible to detect some genes whose function is unknown.
      The data reported are, to our knowledge, the first genetic portrait of a
      zirconium oxide surface. They can be relevant to better understand the molecular
      mechanism of biocompatibility and as a model for comparing other materials.

PMID- 14585710
TI  - Lack of OH in nanocrystalline apatite as a function of degree of atomic order:
      implications for bone and biomaterials.
AB  - Using laser Raman microprobe spectroscopy, we have characterized the degree of
      hydroxylation and the state of atomic order of several natural and synthetic
      calcium phosphate phases, including apatite of biological (human bone, heated
      human bone, mouse bone, human and boar dentin, and human and boar enamel),
      geological, and synthetic origin. Common belief holds that all the studied phases
      are hydroxylapatite, i.e., an OH-containing mineral with the composition
      Ca10(PO4)6(OH)2. We observe, however, that OH-incorporation into the apatite
      crystal lattice is reduced for nanocrystalline samples. Among the biological
      samples, no OH-band was detected in the Raman spectrum of bone (the most
      nanocrystalline biological apatite), whereas a weak OH-band occurs in dentin and
      a strong OH-band in tooth enamel. We agree with others, who used NMR, IR
      spectroscopy, and inelastic neutron scattering, that-contrary to the general
      medical nomenclature-bone apatite is not hydroxylated and therefore not
      hydroxylapatite. Crystallographically, this observation is unexpected; it
      therefore remains unclear what atom(s) occupy the OH-site and how charge balance
      is maintained within the crystal. For non-bone apatites that do show an OH-band
      in their Raman spectra, there is a strong correlation between the concentration
      of hydroxyl groups (based on the ratio of the areas of the 3572 deltacm(-1) OH
      peak to the 960 deltacm(-1) P-O phosphate peak) and the crystallographic degree
      of atomic order (based on the relative width of the 960 deltacm(-1) P-O phosphate
      peak) of the samples. We hypothesize that the body biochemically imposes a
      specific state of atomic order and crystallinity (and, thus, concentration of
      hydroxyl) on its different apatite precipitates (bone, dentin, enamel) in order
      to enhance their ability to carry out tissue-specific functions.

PMID- 14585711
TI  - Platelet adhesion on silicon modified hydrogenated amorphous carbon films.
AB  - We have investigated the effect of changes in microstructure, surface energy,
      surface charge condition and electronic conduction on the interaction of human
      platelets with silicon modified hydrogenated amorphous carbon films (a-C:H:Si or
      Si-DLC). Results based on Raman spectroscopy, Scanning electron microscopy, X-ray
      photo-electron spectroscopy, surface energy measurements, electrical resistivity,
      contact potential difference, and thermal annealing indicates a correlation
      between some of the measured values and the interaction of the films with human
      blood platelets. Statistical analysis of platelet aggregation on the films using
      the Student's t-test indicated differences between platelet aggregation on the
      modified films compared to the as-deposited film at a p-value of <0.05.

PMID- 14585712
TI  - In vivo and in vitro degradation of poly(ether ester) block copolymers based on
      poly(ethylene glycol) and poly(butylene terephthalate).
AB  - Two in vivo degradation studies were performed on segmented poly(ether ester)s
      based on polyethylene glycol (PEG) and poly(butylene terephthalate) (PBT)
      (PEOT/PBT). In a first series of experiments, the in vivo degradation of melt
      pressed discs of different copolymer compositions were followed up for 24 weeks
      after subcutaneous implantation in rats. The second series of experiments aimed
      to simulate long-term in vivo degradation. For this, PEOT/PBT samples were pre
      degraded in phosphate buffer saline (PBS) at 100 degrees C and subsequently
      implanted. In both series, explanted materials were characterized by intrinsic
      viscosity measurements, mass loss, proton nuclear magnetic resonance spectroscopy
      (1H-NMR) and differential scanning calorimetry (DSC). In both studies the
      copolymer with the higher PEO content degraded the fastest, although all
      materials degraded relatively slowly. To determine the nature of the degradation
      products formed during hydrolysis of the copolymers, 1000 PEOT71PBT29 (a
      copolymer based on PEG with a molecular weight of 1000 g/mol and 71 wt% of PEO
      containing soft segments) was degraded in vitro at 100 degrees C in phosphate
      buffer saline (PBS) during 14 days. The degradation products present in PBS were
      analyzed by 1H-NMR and high performance liquid chromatography/mass spectroscopy
      (HPLC/MS). These degradation products consisted of a fraction with high contents
      of PEO that was soluble in PBS and a PEOT/PBT fraction that was insoluble at room
      temperature. From the different in vitro and in vivo degradation experiments
      performed, it can be concluded that PEOT/PBT degradation is a slow process and
      generates insoluble polymeric residues with high PBT contents.

PMID- 14585713
TI  - Soft tissue reactions of different biodegradable polylactide implants.
AB  - Soft tissue reactions resulting from biodegradable polylactide implants to bone
      have not been adequately examined during their 3-year degradation period. An
      osteotomy was performed on the medial femoral condyle of 36 sheep and secured by
      either three poly-L-DL-lactide pins (70/30) (Polypin) or three composite pins
      [10% beta-tricalcium phosphate (beta-TCP) (90/10)]. A histological examination
      was performed on the synovial membrane and lymph nodes after 3, 18 and 36 months.
      After 18 months two non-specific, minor reactions of the synovial membrane were
      observed in the composite pin group. In both groups different reactions of both
      inguinal lymph nodes were observed. These had no statistical relevance and could
      not be clearly attributed to the implants. Due to the slow degradation process of
      biodegradable polylactide implants, there is no clinically relevant inflammation
      of either joint or lymph nodes. The addition of 10% beta-TCP did not result in
      any significant enhancement.

PMID- 14585714
TI  - The effect of COX-2 inhibitors on periprosthetic osteolysis.
AB  - We aimed to test the hypothesis that COX(cyclooxygenase)-2 inhibitors suppress
      periprosthetic osteolysis in a rabbit model. Porous coated titanium bar was
      inserted into distal femur of 24 skeletally mature New Zealand white rabbits. The
      rabbits were randomized into 3 groups. Group I (8 rabbits) was the control group.
      In Group II (8 rabbits), 5mg of ultrahigh molecular weight polyethylene particles
      was inserted along with prosthesis. In Group III (8 rabbits), the same procedure
      as in Group II was done and a COX-2 inhibitor (celecoxib, Pharmacia: 10mg/day)
      was administered for 7 weeks. Rabbits were sacrificed after 8 weeks of
      implantation. Gross, radiological, histological, and immunohistochemical
      assessments were done. Gross examination showed that one implant in Group II was
      loose. In radiological evaluation, focal osteolysis was found in 2 rabbits of
      Group II and 1 rabbit of Group III. Linear osteolysis was found in 2 rabbits of
      Group II and 1 rabbit of Group III. On histological examination, focal area of
      granulation tissue laden with macrophages was observed in 6 rabbits of Group II
      and 6 rabbits of Group III. The mean number of osteoclasts as demonstrated by
      tartarate positive acid phosphatase staining was 0.5+/-0.5 in Group I, 6.5+/-2.7
      in Group II, 3.6+/-2.6 in Group III (p<0.05). Immunohistochemical staining for
      inducible nitric acid synthase and COX-2 did not show significant difference
      between Groups II and III. The overall results of this study suggest that COX-2
      inhibitors in the therapeutic dose may have a place in suppressing the process of
      periprosthetic osteolysis.

PMID- 14585715
TI  - Biomimetic nucleation and growth of CaCO3 in hydrogels incorporating carboxylate
      groups.
AB  - Poly-acrylamide hydrogels were modified by copolymerization with acrylic acid and
      used as growth medium for CaCO3 in a double-diffusion arrangement. The
      carboxylate functionalities in the gel network facilitate the nucleation of a
      multitude of small crystallites of vaterite and calcite, which are temporarily
      stabilized even while supersaturation is increasing within the hydrogel. After an
      extended induction period the rapid spherulitic growth of calcite crystals along
      their c-axis is observed yielding spheres with diameters exceeding 300 microm. In
      the center of those aggregates disordered, porous regions can be identified as
      starting point of this rapid crystallization. The results are compared to
      previous studies on native poly-acrylamide hydrogels and networks modified with 
      SO(3)H functional groups. The mineralization mechanism is significantly altered
      by specific interactions between the -COOH functionalized network and the
      evolving mineral phase.

PMID- 14585716
TI  - Catalytic generation of nitric oxide from nitrite at the interface of polymeric
      films doped with lipophilic CuII-complex: a potential route to the preparation of
      thromboresistant coatings.
AB  - A novel approach potentially useful for the development of more thromboresistant
      polymeric materials is examined. The method is based on the catalytic generation
      of nitric oxide (NO) via Cu(I) mediated reduction of nitrite ions. Preliminary
      solution phase studies demonstrate that ascorbate or thiolate anions can generate
      Cu(I) from Cu(II) with subsequent catalytic conversion of any nitrite ions
      present to NO by the unstable Cu(I) species. Incorporation of this same chemistry
      within a hydrophobic polymeric material requires immobilizing Cu(II) ions into a
      polymeric phase via use of a lipophilic Cu(II) chelating ligand (dibenzo [e,k]
      2,3,8,9-tetraphenyl-1,4,7,10-tetraaza-cyclododeca-1,3,7,9-tetraene (DTTCT)). It
      is shown that this complex can be reduced to its Cu(I) form by appropriate
      reducing equivalents present in the bathing solution. The resulting Cu(I) complex
      can then reduce nitrite to NO with the NO generation occurring at the
      polymer/solution interface at physiological pH. Data from chemiluminescence
      experiments indicate that the flux of NO at the polymer surface is comparable to
      that of endothelial cells (>/=1x10(-10)mol/cm(2)min) when 0.5mM nitrite/1mM
      ascorbate are present in the bathing solution. Potentially more useful NO
      generation can be achieved by doping the polymer film with the Cu(II) complex
      along with a lipophilic quaternary ammonium nitrite salt. In this case reducing
      equivalents within the aqueous phase enable the nitrite derived from the polymer
      to be converted into NO by the Cu(II/I) ligand complex. Films of this type are
      shown to generate NO for at least 6h in PBS buffer with fluxes on the order of
      1.5x10(-10)mol/cm(2)min. Physiologically relevant levels of NO release are also
      shown to exist at the polymer interface when films are soaked in fresh plasma as
      well as undiluted whole blood, indicating that endogenous reducing equivalents
      present in blood can efficiently reduce the Cu(II)-ligand within the polymer
      film. The prospects of using these new NO releasing films to devise more
      biocompatible polymeric coatings for biomedical applications are discussed.

PMID- 14585717
TI  - Humoral immune responses to model antigen co-delivered with biomaterials used in
      tissue engineering.
AB  - A model shed antigen, ovalbumin (OVA), was co-delivered with polymeric
      biomaterial carrier vehicles in C57BL6 mice to test whether the presence of the
      biomaterial acted as an adjuvant in the immune response towards the associated
      antigen. The biomaterials tested were non-biodegradable polystyrene
      microparticles and biodegradable 50:50 or 75:25 poly(lactic-co-glycolic acid)
      (PLGA) microparticles or scaffolds. For each biomaterial carrier vehicle, to
      assess the resulting time-dependent systemic humoral immune response towards the
      co-delivered OVA, the OVA-specific IgG concentration and isotypes (IgG2a or IgG1,
      indicating a predominant Th1 or Th2 response, respectively) were determined using
      ELISA. OVA co-delivered with biomaterial carrier vehicles supported a moderate
      humoral immune response that was maintained for the 18-week duration of the
      experiment. This humoral immune response was primarily Th2 helper T cell
      dependent as indicated by the predominant IgG1 isotype. Furthermore, this humoral
      immune response was not material chemistry-dependent within the material set
      tested here. With the presence of the biomaterial resulting in an enhancement of
      the humoral immune response to co-delivered antigen, it appears that the
      biomaterial acts as an adjuvant in the development of an adaptive immune response
      to co-delivered antigen.

PMID- 14585718
TI  - In vitro and in vivo transfection efficiency of a novel ultradeformable cationic
      liposome.
AB  - Cationic lipids have been often used as one of the major components in making
      most promising non-viral gene delivery systems, whereas sodium cholate, a
      surfactant so-called edge activator has been used in preparing ultradeformable
      and ultraflexible liposomes called Transfersomes. Using both a cationic lipid,
      DOTAP and sodium cholate, a novel formulation of ultradeformable cationic
      liposome (UCL) has been prepared. The average particle size of this formulation
      was approximately 80 nm. The physical and chemical stabilities at two different
      temperatures (4 degrees C and 20 degrees C) were also evaluated for 60 days. The
      ultradeformability of new formulation was also assessed, and it has been proved
      that the formulation is deformable. In vitro transfection efficiency of plasmid
      DNA/UCL was assessed by the expression of green fluorescent protein (GFP) in four
      cell lines, OVCAR-3 (human ovarian carcinoma cells), HepG2 (human hepatoma
      cells), H-1299 (human lung carcinoma cells) and T98G (human brain carcinoma
      cells). The optimal ratio of DNA to liposome for maximal transfection efficiency
      was 1:14 (w/w) in all the cell lines except for the human brain carcinoma cells.
      The same formulation was tested for in vivo transfection efficiency and its
      retention time within the organs by applying the DNA/UCL complexes on hair
      removed dorsal skin of mice non-invasively. It was found that genes were
      transported into several organs for 6 days once applied on intact skin.

PMID- 14585719
TI  - Precipitation casting of polycaprolactone for applications in tissue engineering
      and drug delivery.
AB  - Microporous materials have been produced by gradual precipitation from solutions
      of poly(epsilon-caprolactone) (PCL) in acetone induced by solvent extraction
      across a semi-permeable PCL membrane which is formed in situ at the polymer
      solution/non-solvent interface. Microparticulates of hydroxyapatite and inulin
      polysaccharide, respectively, were incorporated in precipitation cast PCL
      matrices to illustrate potential applications in hard tissue repair and
      macromolecular drug release. Microporous PCL and HA filled PCL materials were
      found to provide a favourable surface for attachment and growth of primary human
      osteoblasts in cell culture. The in vitro degradation characteristics of
      microporous PCL and inulin/PCL materials in PBS at 37 degrees C were monitored
      over 45 months. Microporous PCL demonstrated zero weight loss, minor changes in
      molecular weight characteristics and a fairly constant indentation resistance of
      around 1 MN/m2. Inulin-loaded PCL materials exhibited a total weight loss of
      approximately 17% after 12 months in PBS. The indentation resistance decreased by
      50% from an initial value of 28 MN/m2 in the first 2 months and then remained
      stable. Precipitation cast materials based on PCL are expected to be useful for
      formulating long-term, controlled release devices for bioactive molecules such as
      growth factors and hormones and extended-residence supports for cell growth and
      tissue development.

PMID- 14585720
TI  - Bioactive glass as a drug delivery system of tetracycline and tetracycline
      associated with beta-cyclodextrin.
AB  - The aim of this study was to evaluate the physical-chemical properties, in vivo
      biocompatibility and antimicrobial activity of bioactive glasses (BG) used as a
      controlled release device for tetracycline hydrochloride and an inclusion complex
      formed by tetracycline and beta-cyclodextrin at 1:1 molar ratio. The BG as well
      as their compounds loaded with tetracycline (BT) and tetracycline:beta
      cyclodextrin (BTC) were characterized by FTIR spectroscopy, X-ray powder
      diffraction, differential scanning calorimetry and by scanning electron
      microscopy and energy dispersive spectroscopy. The in vivo test was carried out
      with female mice split into three groups treated with bioactive glass either
      without drugs, or associated with tetracycline, or with tetracycline:beta
      cyclodextrin by subcutaneous implantation. The histological examination of tissue
      at the site of implantation showed moderate inflammatory reactions in all groups
      after 72 h. The bacterial effect was tested on A. actinomycetemcomitans suspended
      in BHI broth, with or without bioactive particles. A considerable bacteriostatic
      activity was found with BT and BTC glasses, as compared to plain glass. The
      presence of cyclodextrin was important to slow down the release of tetracycline
      for a long period of time and it was verified that the presence of tetracycline
      or its inclusion complex, tetracycline:beta-cyclodextrin, did not affect the
      bioactivity of the glass.

PMID- 14585721
TI  - The functional expression of human bone-derived cells grown on rapidly resorbable
      calcium phosphate ceramics.
AB  - The use of biodegradable bone substitutes is advantageous for alveolar ridge
      augmentation, since it avoids second-site surgery for autograft harvesting. This
      study examines the effect of novel, rapidly resorbable calcium phosphates on the
      expression of bone-related genes and proteins by human bone-derived cells (HBDC)
      and compares this behavior to that of tricalciumphosphate (TCP). Test materials
      were alpha-TCP, and four materials which were created from beta-Rhenanite and its
      derivatives: R1-beta-Rhenanite (CaNaPO(4)); R1/M2 composed of CaNaPO(4) and
      MgNaPO(4); R1+SiO(2) composed of CaNaPO(4) and 9% SiO(2) (wt%); and R17
      Ca(2)KNa(PO(4))(2). HBDC were grown on the substrata for 3, 5, 7, 14 and 21 days,
      counted and probed for various mRNAs and proteins (Type I collagen, osteocalcin,
      osteopontin, osteonectin, alkaline phosphatase and bone sialoprotein). All
      substrata supported continuous cellular growth for 21 days. At day 21, surfaces
      of R1+SiO(2) and R17 had the highest number of HBDC. At 14 and 21 days, cells on
      R1 and on R1+SiO(2) displayed significantly enhanced expression of all osteogenic
      proteins. Since all novel calcium phosphates supported cellular proliferation
      together with expression of bone-related proteins at least as much as TCP, these
      ceramics can be regarded as potential bone substitutes. R1 and R1+SiO(2) had the
      most effect on osteoblastic differentiation, thus suggesting that these materials
      may possess a higher potency to enhance osteogenesis than TCP.

PMID- 14585722
TI  - The release profiles and bioactivity of parathyroid hormone from poly(lactic-co
      glycolic acid) microspheres.
AB  - Poly(lactic-co-glycolic acid) (PLGA) microspheres containing bovine serum albumin
      (BSA) or human parathyroid hormone (PTH)(1-34) were prepared using a double
      emulsion method with high encapsulation efficiency and controlled particle sizes.
      The microspheres were characterized with regard to their surface morphology,
      size, protein loading, degradation and release kinetics, and in vitro and in vivo
      assessments of biological activity of released PTH. PLGA5050 microspheres
      degraded rapidly after a 3-week lag time and were degraded completely within 4
      months. In vitro BSA release kinetics from PLGA5050 microspheres were
      characterized by a burst effect followed by a slow release phase within 1-7 weeks
      and a second burst release at 8 weeks, which was consistent with the degradation
      study. The PTH incorporated PLGA5050 microspheres released detectable PTH in the
      initial 24h, and the released PTH was biologically active as evidenced by the
      stimulated release of cAMP from ROS 17/2.8 osteosarcoma cells as well as
      increased serum calcium levels when injected subcutaneously into mice. Both in
      vitro and in vivo assays demonstrated that the bioactivity of PTH was maintained
      largely during the fabrication of PLGA microspheres and upon release. These
      studies illustrate the feasibility of achieving local delivery of PTH to induce a
      biologically active response in bone by a microsphere encapsulation technique.

PMID- 14585723
TI  - Biocompatibility and strength properties of nitinol shape memory alloy suture in
      rabbit tendon.
AB  - Nitinol (NiTi) is a promising new tendon suture material with good strength, easy
      handling and good super-elastic properties. NiTi sutures were implanted for
      biocompatibility testing into the right medial gastrocnemius tendon in 15 rabbits
      for 2, 6 and 12 weeks. Additional sutures were implanted in subcutaneous tissue
      for strength measurements in order to determine the effect of implantation on
      strength properties of NiTi suture material. Braided polyester sutures (Ethibond)
      of approximately the same diameter were used as control. Encapsulating membrane
      formation around the sutures was minimal in the case of both materials. The
      breaking load of NiTi was significantly greater compared to braided polyester.
      Implantation did not affect the strength properties of either material.

PMID- 14585724
TI  - Biological oxygen apparent transmissibility of hydrogel contact lenses with and
      without organosilicon moieties.
AB  - The instrument oxygen transmissibility (IOT) of organosilicon hydrogels, measured
      by electrochemical procedures, is 5-10 times larger than that of conventional
      hydrogels. A method is described that allows the estimation of the oxygen tension
      at the lens-cornea interface for closed- and open-eyelids situations by combining
      the IOT of the hydrogels and corneal parameters such as corneal thickness,
      corneal permeability and oxygen flux across the cornea. From these results the
      biological oxygen apparent transmissibility (BOAT) is obtained, an important
      parameter which an multiplication with the pressure of oxygen on the external
      part of the lens gives the oxygen flux onto the cornea. Contact lenses with
      oxygen transmissibility higher than 100 Dk/t units [1 Dk/t unit=10(-9) [cm(3)
      O(2) (STp) cm(-2)s(-1)(mmHg)(-1)] posses a large oxygen tension at the lens
      cornea interface that substantially reduces the oxygen flux onto the cornea.
      Lenses whose oxygen transmissibility is lower than 50 Dk/t units allow a rather
      small oxygen flux onto the cornea under closed eyelids condition that prevent
      their use for extended wear.

PMID- 14585725
TI  - Water sorption characteristics of light-cured dental resins and composites based
      on Bis-EMA/PCDMA.
AB  - The water uptake characteristics of resins and composites based on an ethoxylated
      bisphenol A glycol dimethacrylate (Bis-EMA) and a polycarbonate dimethacrylate
      (PCDMA) were studied in detail. Polydimethacrylate resins were prepared by
      photopolymerization of the neat monomers and mixtures of them with various weight
      ratios, using the camphoroquinone/N,N-dimethylaminoethyl methacrylate system as
      initiator, while the composites were prepared from the light-curing of commercial
      samples (Sculpt-It and Alert). Water sorption/desorption was examined both in
      equilibrium and dynamic conditions in two adjacent sorption-desorption cycles.
      The equilibrium water uptake from all resins was very small with a trend to
      increase as the amount of PCDMA was increased. The inverse effect was observed in
      the solubility values. The composites studied exhibited also very low water
      uptake values in comparison to other composite materials reported in the
      literature. It was also observed that the equilibrium uptake decreased with
      increasing filler loading. Slightly larger equilibrium water uptake and much
      smaller solubility values were obtained during the second sorption-desorption
      cycle in comparison to the first one. Concerning the sorption rate data, it was
      observed that the resin materials followed Fickian diffusion during almost the
      whole sorption or desorption curve, while the composites showed this behavior
      until only M(t)/M( infinity ) congruent with 0.5. The diffusion coefficients
      calculated for the resins were larger than those of the composites and always
      higher during desorption compared to sorption. The values of the diffusion
      coefficients for both resins and composites were in the same order of magnitude
      with the values of the corresponding materials reported in the literature.

PMID- 14585726
TI  - Carcinogenic and systemic health effects associated with arsenic exposure--a
      critical review.
AB  - Arsenic and arsenic containing compounds are human carcinogens. Exposure to
      arsenic occurs occupationally in several industries, including mining, pesticide,
      pharmaceutical, glass and microelectronics, as well as environmentally from both
      industrial and natural sources. Inhalation is the principal route of arsenic
      exposure in occupational settings, while ingestion of contaminated drinking water
      is the predominant source of significant environmental exposure globally.
      Drinking water contamination by arsenic remains a major public health problem.
      Acute and chronic arsenic exposure via drinking water has been reported in many
      countries of the world, where a large proportion of drinking water is
      contaminated with high concentrations of arsenic. General health effects that are
      associated with arsenic exposure include cardiovascular and peripheral vascular
      disease, developmental anomalies, neurologic and neurobehavioural disorders,
      diabetes, hearing loss, portal fibrosis, hematologic disorders (anemia,
      leukopenia and eosinophilia) and multiple cancers: significantly higher
      standardized mortality rates and cumulative mortality rates for cancers of the
      skin, lung, liver, urinary bladder, kidney, and colon in many areas of arsenic
      pollution. Although several epidemiological studies have documented the sources
      of exposure and the global impact of arsenic contamination, the mechanisms by
      which arsenic induces health effects, including cancer, are not well
      characterized. Further research is needed to provide a better understanding of
      the pathobiology of arsenic-induced diseases and to better define the toxicologic
      pathology of arsenic in various organ systems. In this review, we provide and
      discuss the underlying pathology and nature of arsenic-induced lesions. Such
      information is critical for understanding the magnitude of health effects
      associated with arsenic exposure throughout the world.

PMID- 14585727
TI  - Effects of exogenous melatonin--a review.
AB  - The results of studies on the effect of pineal indole hormone melatonin on the
      life span of mice, rats, fruit flies, and worms are critically reviewed. In mice,
      long-term administration of melatonin was followed by an increase in their life
      span in 12 experiments and had no effect in 8 of 20 different experiments. In D.
      melanogaster, the supplementation of melatonin to the nutrient medium during
      developmental stages gave contradictory results, but when melatonin was added to
      food throughout the life span, an increase in the longevity of fruit flies has
      been observed. Melatonin decreased the survival of C. elegans but increased the
      clonal life span of planaria Paramecium tertaurelia. Available data suggest
      antioxidant and atherogenic effects of melatonin. Melatonin alone turned out to
      be neither toxic nor mutagenic in the Ames test and revealed clastogenic activity
      in high concentration in the COMET assay. Melatonin inhibits mutagenesis induced
      by irradiation and by indirect chemical mutagens and inhibits the development of
      spontaneous and chemical-induced tumors in mice and rats. Further studies and
      clinical trials are needed to verify that melatonin is both safe and has
      geroprotector efficacy for humans.

PMID- 14585729
TI  - Mono-iodoacetate-induced histologic changes in subchondral bone and articular
      cartilage of rat femorotibial joints: an animal model of osteoarthritis.
AB  - Osteoarthritis (OA) is a degenerative joint disease characterized by joint pain
      and a progressive loss of articular cartilage. Studies to elucidate the
      pathophysiology of OA have been hampered by the lack of a rapid, reproducible
      animal model that mimics both the histopathology and symptoms associated with the
      disease. Injection of mono-iodoacetate (MIA), an inhibitor of glycolysis, into
      the femorotibial joint of rodents promotes loss of articular cartilage similar to
      that noted in human OA. Here, we describe the histopathology in the subchondral
      bone and cartilage of rat (Wistar) knee joints treated with a single intra
      articular injection of MIA (1 mg) and sacrificed at 1, 3, 5, 7, 14, 28, and 56
      days postinjection. Histologically, the early time points (days 1-7) were
      characterized by areas of chondrocyte degeneration/necrosis sometimes involving
      the entire thickness of the articular cartilage in the tibial plateaus and
      femoral condyles. Changes to the subchondral bone, as evidenced by increased
      numbers of osteoclasts and osteoblasts, were noted at by day 7. By 28 days, there
      was focal fragmentation and collapse of bony trabeculae with fibrosis and
      increased osteoclastic activity. By 56 days there were large areas of bone
      remodeling evidenced by osteoclastic bone resorption and newly formed trabeculae
      with loss of marrow hematopoietic cells. Subchondral cysts and subchondral
      sclerosis were present in some rats. In conclusion, intra-articular injection of
      MIA induces loss of articular cartilage with progression of subchondral bone
      lesions that mimic those of OA. This model offers a rapid and minimally invasive
      method to reproduce OA-like lesions in a rodent species.

PMID- 14585728
TI  - Molecular mechanisms of renal tissue repair in survival from acute renal tubule
      necrosis: role of ERK1/2 pathway.
AB  - Our earlier studies with S-(1,2-dichlorovinyl)-L-cysteine (DCVC) showed that
      prior administration of a low priming dose of 15 mg/kg, i.p. to mice, given 72
      hours before administration of a normally lethal dose of DCVC (75 mg/kg, i.p.)
      led to renal tubule necrosis, however sustained renal tubule regeneration was
      observed and these mice recovered from renal failure and survived. The objective
      of the present study was to investigate the role of extracellular signal
      regulated kinase (ERK) pathway in this autoprotection model. Following the
      priming dose of DCVC, IL-6 protein and mRNA increased markedly as early as 1 hour
      after dosing, peaking at 3 hours with a 1.5-fold increase in plasma.
      Immunocytochemistry on kidney sections using specific antibodies against TGF
      alpha, HB-EGF, EGFr, IGF-1Rbeta, Grb-2, and phospho-p44/42 MAP kinase (ERK1/2)
      revealed a significantly higher staining of these molecules 3 to 72 hours after
      dosing, indicating up regulation of the ERK pathway. Following a lethal dose of
      DCVC (75 mg/kg) the early increase in these signaling molecules was not
      sustained, being markedly reduced 24 and 36 hours after dosing, leading to
      inhibition of S-phase DNA synthesis, cell division and renal tubule repair. In
      contrast, prior treatment with a low dose of DCVC, followed by a high dose led to
      a sustained stimulation of the renal ERK pathway, renal tubule regeneration and
      recovery from acute renal failure. These results suggest that a sustained
      activation of the ERK1/2 pathway may be a key factor in enabling a continued
      renal tubule repair and hence protection from the progressive phase of DCVC
      induced acute renal tubular necrosis in the mouse.

PMID- 14585730
TI  - Sequential alteration of apoptosis, p53 expression, and cell proliferation in the
      rat pancreas treated with 4-hydroxyaminoquinoline 1-oxide.
AB  - Changes in p53 expression, apoptosis and cell proliferation after treatment with
      4-hydroxyaminoquinoline 1-oxide (4HAQO) were investigated in the rat pancreas and
      liver, target and nontarget organs for tumorigenesis, respectively. Male rats
      were given a single intravenous injection of 4HAQO at a dose of 20 mg/kg body
      weight and control rats received vehicle alone and were euthanized after 2-72
      hours. Pancreata and livers were removed for histopathological examination,
      immunohistochemistry for p53 protein, PCNA and Ki-67, and TUNEL labeling and
      electron microscopic observation for detecting apoptosis. In the pancreas, p53
      expression and apoptosis were significantly increased first at 4 and 6 hours,
      respectively, while no change was evident in the liver. The rates peaked at 24
      hours, consistent with the peak for PCNA-labeling, while Ki-67-labeling rates
      peaked at 72 hours. Electron microscopically, apoptotic changes in pancreatic
      acinar cells were observed after 2 hours. No significant apoptosis, p53
      expression or cell proliferation were noted in the pancreatic tissues of the
      control rats nor in liver cells regardless of 4HAQO treatment. Taken together
      with our previous data, the results suggest that apoptosis, p53 expression, and
      enhanced cell replication are closely related phenomena involved in the
      carcinogenesis of 4HAQO following DNA adduct formation.

PMID- 14585731
TI  - Rapid emergence of mammary preneoplastic and malignant lesions in human c-Ha-ras
      proto-oncogene transgenic rats: possible application for screening of
      chemopreventive agents.
AB  - For comparison of mammary gland whole mounts with examination of 2 histologic
      sections of mammary gland, 56 Hras128 rats were intravenously injected with 50
      mg/kg body weight of N-methyl-N-nitrosourea at 50 days of age and then sacrificed
      at days 5, 10, 15, 20, 25, and 56. Comparison of detection sensitivity between
      the whole mounts and histologic sections revealed no lesions apparent in whole
      mounts on day 10, although intraductal proliferation was clearly detected in
      histologic sections in 44% of treated rats. Proliferative lesions were first
      detected in whole mounts at a 44% incidence on day 15, while intraductal
      proliferations and atypical hyperplasias were apparent in the sections at 89% and
      44% incidences, respectively. On day 20, atypical hyperplasias and small
      adenocarcinomas in histologic sections were found in almost all animals. In
      conclusion, examination of 2 histologic sections from mammary tissues was found
      to be practical for detection of small malignant lesions as early as 15 days
      after MNU injection, and suppressive effects of soy isoflavones were clearly
      evident within 20 days after carcinogen exposure. These results suggest that this
      model has practical utility for short-term screening of chemopreventive agents
      for mammary carcinogenesis.

PMID- 14585732
TI  - Apoptosis and nitrative stress associated with phosphodiesterase inhibitor
      induced mesenteric vasculitis in rats.
AB  - Nitric oxide may play a role in phosphodiesterase (PDE) inhibitor-induced rat
      mesenteric vasculitis. The present study was conducted to identify cellular
      sources of iNOS, determine the distribution of nitrotyrosine (NT) residues as a
      footprint of peroxynitrite (ONOO-) production, and evaluate their association
      with vascular apoptosis. To dissociate primary events from secondary changes
      associated with the inflammatory response, rats were given the PDE IV inhibitor
      CI-1018 orally at 750 mg/kg alone or concurrently with dexamethasone (DEX)
      intraperitoneally at 1 mg/kg for 4-5 days. Neutrophil (PMN) involvement in
      apoptosis was investigated in CI-1018 treated rats dosed with rabbit anti-rat PMN
      serum (APS). iNOS expression, NT residues, and caspase-3 were detected by immuno
      histochemistry. Apoptosis was evaluated by TUNEL assay. CI-1018 induced vascular
      lesions were associated with iNOS expression in endothelial cells and
      inflammatory infiltrates; NT was evident only in the latter. Caspase-3 and TUNEL
      positive staining were prominent only in medial smooth muscle cells (SMC) from CI
      1018-treated rats and only when associated with active inflammation. iNOS- and NT
      positive inflammatory cells were present in close proximity to SMC with caspase-3
      staining. Inflammatory infiltrates were absent in rats given DEX with minimal SMC
      necrosis and hemorrhage remained. DEX eliminated apoptosis and immunoreactivity
      associated with caspase-3, iNOS, and NT. APS depletion of PMNs decreased the
      incidence and severity of vasculitis but failed to abolish completely caspase-3
      immunoreactivity. Expression patterns for caspase-3, iNOS, and NT demonstrated
      that nitrative stress is a prominent feature of PDE inhibitor-induced vasculitis,
      with a possible role in medial SMC apoptosis. Further, medial SMC apoptosis may
      not be a primary event, but instead may be secondary to the inflammatory
      response.

PMID- 14585733
TI  - Iron lactate-induced osteomalacia in association with osteoblast dynamics.
AB  - Osteomalacia was induced in rats fed a diet containing 50,000 ppm (5%) iron
      lactate for 13 weeks. The histopathology and histomorphometrical dynamics of
      osteoblasts under this condition were examined. Bone histomorphometry of the
      proximal tibial metaphysis revealed that the osteoblast surface, osteoid volume,
      osteoid surface and labeled surface ratio, which are the parameters of bone
      formation had increased. The blood chemistry revealed the greatest elevation in
      the osteocalcin level; however, the parathyroid hormone (PTH) secretion and
      inorganic phosphorus level were very low. From the serum biochemical,
      histopathological and histomorphometrical findings, the bone lesion in iron
      lactate-overloaded rats was considered to be similar to low turnover osteomalacia
      showing decreased trabeculae in secondary spongiosa and increased lamellar
      osteoid. Furthermore, an iron-positive reaction was detected at the interface
      between osteoid and mineralized bone. In the bone lesions induced by chronic iron
      overload, osteoblast recruitment exceeded that of mineralization or,
      alternatively, the iron within osteoblasts along the trabecular bone suppressed
      the remodeling and led to an increase in osteoid thickness.

PMID- 14585734
TI  - Morphology of nasal lesions in F344/N rats following chronic inhalation exposure
      to naphthalene vapors.
AB  - Naphthalene (CAS No. 91-20-3) administered by inhalation at concentrations of 10,
      30, or 60 ppm for 6 hours per day, 5 days per week for 105 weeks caused
      nonneoplastic and neoplastic effects in nasal respiratory and olfactory regions
      of male and female F344/N rats. Non-neoplastic nasal effects were characterized
      by an increase in the incidence and severity of a complex group of lesions,
      including atypical hyperplasia, atrophy, chronic inflammation, and hyaline
      degeneration of olfactory epithelium; hyperplasia, squamous metaplasia, hyaline
      degeneration, and goblet cell hyperplasia of the respiratory epithelium; and
      hyperplasia and squamous metaplasia of mucosal glands. Neoplastic effects were
      characterized by the induction of two types of rare primary nasal tumors,
      olfactory neuroblastomas and respiratory epithelial adenomas. The incidences of
      olfactory neuroblastomas in males at 0 ppm, 10 ppm, 30 ppm, and 60 ppm were,
      respectively, 0%, 0%, 8%, and 6%, whereas in females they were 0%, 4%, 6%, and
      24%. The incidences of respiratory epithelial adenomas in males at 0 ppm, 10 ppm,
      30 ppm, and 60 ppm were, respectively, 0%, 12%, 17%, and 31% and in females 0%,
      0%, 8%, and 4%. The olfactory neuroblastomas and respiratory epithelial adenomas
      were considered carcinogenic effects related to naphthalene exposure based on
      their relatively high incidence in exposed rats, their absence in concurrent
      control rats and NTP historical controls, and their rare spontaneous occurrence
      in rats of any strain.

PMID- 14585735
TI  - Effects of granulocyte colony-stimulating factor (G-CSF) on bleomycin-induced
      lung injury of varying severity.
AB  - We evaluated the effects of granulocyte colony-stimulating factor (G-CSF) on
      bleomycin (BLM)-induced lung injury that developed diffuse alveolar damage and
      subsequent pulmonary fibrosis (PF) of varying severity. G-CSF (100 microg/kg/day)
      was administered subcutaneously to BLM (0.2, 20, 2,000 microg)-treated or 
      untreated rats for 3 or 14 days. In the BLM 0.2 microg group, slight alveolar
      mononuclear cell infiltration was observed, although PF was not noted. In the BLM
      20-microg and 2,000-microg groups, diffuse alveolar damage along with neutrophil
      infiltration and subsequent PF were observed. In the saline + G-CSF group and BLM
      0.2 microg + G-CSF group, a marked increase in the number of alkaline phosphatase
      (ALP)-positive neutrophils was noted in the alveolar capillaries, although there
      was neither neutrophil infiltration in alveoli nor exacerbation of lung injury.
      In the BLM 20 microg + G-CSF and BLM 2,000 microg + G-CSF groups, an exacerbation
      of lung injury along with an increase in the number of ALP-positive neutrophils
      in the alveoli was observed. These results indicate that the administration of G
      CSF to rats with slight lung injury bearing no PF does not exacerbate the lung
      injury. The exacerbating effects of G-CSF seem to be associated not only with the
      marked infiltration of activated neutrophils but also with the severity of
      underlying lung injury.

PMID- 14585736
TI  - Effect of diet and animal care/housing protocols on body weight, survival, tumor
      incidences, and nephropathy severity of F344 rats in chronic studies.
AB  - Diet is an important environmental factor affecting body weight, survival, and
      age-related diseases of rodents. The NIH-07 open formula diet was the diet used
      in the National Toxicology Program's (NTPs) rodent carcinogenicity studies from
      1980 to 1994. In 1994 the NTP began using a new diet designated the NTP-2000
      diet. This paper compares body weight, survival, tumor incidence, and nephropathy
      severity in untreated control groups of Fischer 344 (F344) rats fed the NTP-2000
      or NIH-07 diets, using data from 22 separate 2-year feed and inhalation studies.
      The feed studies were conducted in 3 different facilities, and all the inhalation
      studies were conducted in a single facility. During feed studies, rats were group
      housed in polycarbonate cages and fed diets in powder (mash) form, while in
      inhalation studies, rats were housed individually in wire mesh cages, and fed
      diets in pelleted form. Survival was significantly (p<0.05) higher in groups fed
      NTP-2000 diet compared to the corresponding groups fed NIH-07 diet, irrespective
      of sex or housing conditions. Use of the NTP-2000 diet was also associated with a
      decreased incidence of pituitary gland tumors in both sexes and decreased
      incidences of adrenal pheochromocytoma and preputial gland tumors in males. The
      incidence and severity of nephropathy was also decreased in animals receiving the
      NTP-2000 diet, especially males. The decreased nephropathy severity and the
      decreased incidence of pituitary gland tumors are likely the major factors
      contributing to the improved survival of rats receiving the NTP-2000 diet
      relative to those given the NIH-07 diet. These data also support earlier findings
      that decreased incidences of adrenal pheochromocytoma are associated with reduced
      nephropathy severity in male F344 rats. Throughout the two-year study female rats
      receiving the NTP-2000 diet were significantly (p<0.05) lighter than those
      receiving the NIH-07 diet. However, it is uncertain if this difference can be
      attributed to the NTP-2000 diet, since implementation of this diet by the NTP
      approximately coincided with changes in the F344 rat production colony that
      resulted in somewhat lighter animals being provided to the NTP. Controls from
      inhalation studies and feed studies differed significantly (p<0.01) in the
      incidence of a variety of tumors, irrespective of diet. This suggests that
      differences in animal care and housing protocols may impact tumor incidence in
      F344 rats, most notably pituitary gland and testis tumors.

PMID- 14585737
TI  - Morphogenesis of postmortem hepatocyte vacuolation and liver weight increases in
      Sprague-Dawley rats.
AB  - Accurate interpretation of microscopic changes in tissues is critical in hazard
      identification and risk assessment. To address a possible confounder, the effects
      of postmortem interval on hepatocyte vacuolation and liver weight were studied in
      fasted and nonfasted Sprague-Dawley rats. Male and female rats (5/sex/interval)
      were euthanized with CO2, weighed, and necropsied either immediately or after
      remaining in the closed CO2 chamber for 5, 10, or 25 minutes after respirations
      ceased. The liver was removed, weighed, and fixed for light microscopy,
      immunohistochemistry, and electron microscopy. The liver weight and liver to body
      weight ratio increased significantly in both male and female rats. Postmortem
      hepatocellular vacuolation was more prominent in males than in females. Both
      fasted and nonfasted males were similarly affected, however, fasted females were
      affected more than nonfasted females at the 25-minute interval.
      Ultrastructurally, intracytoplasmic vacuoles in hepatocytes and/or endothelial
      cells contained electron-lucent material that was morphologically similar to
      plasma in sinusoidal spaces. Results of our study suggest that hepatocyte
      vacuoles were formed in a postmortem time-dependent manner as a result of plasma
      influx into the cytoplasm. This change was associated with hepatic sinusoidal
      congestion and increases in liver weight. Males were more sensitive than females
      to postmortem hepatocyte vacuolation.

PMID- 14585738
TI  - Safety of Aquaflor (florfenicol, 50% type A medicated article), administered in
      feed to channel catfish, Ictalurus punctatus.
AB  - Aquaflor, a feed premix containing the broad spectrum antibacterial agent
      florfenicol (50% w/w), is being developed for use to control enteric septicemia
      (ESC) in channel catfish Ictalurus punctatus caused by the gram-negative
      enterobacterium Edwardsiella ictaluri. The recommended dose of Aquaflor to
      control ESC is 10 mg/kg body weight (BW)/day for 10 days. The study objective was
      to determine the safety of Aquaflor administered in feed to channel catfish at
      doses of 0 (control), 10, 30, and 50 mg/kg BW/day for 20 consecutive days.
      Parameters evaluated included daily mortality, behavioral (appetite,
      distribution, flight/fright response), and water chemistry observations, initial
      and terminal weight measurements, and gross and microscopic pathology. Medicated
      feed consumption was 67-86% of target with group mean doses of 8.5 mg/kg BW/day,
      24.6 mg/kg BW/day, and 34.9 mg/kg BW/day. There were no mortalities or clinically
      observable changes noted at any of the dose levels tested. Aquaflor-related
      changes were limited to the food consumption and histopathology data. Although
      Aquaflor-related decreased feed consumption was noted in the 30 and 50 mg/kg
      BW/day groups, there were no differences in fish growth among the treatment
      groups. Aquaflor-related histopathology findings were limited to a
      histomorphologically evident dose-dependent decrease in
      hematopoietic/lymphopoietic tissue in the anterior kidneys, posterior kidneys,
      and spleens of channel catfish.

PMID- 14585739
TI  - Developmental toxicology studies of WHI-07, a novel nucleoside analogue-based
      dual-function microbicide, administered intravaginally to rabbits.
AB  - The zidovudine derivative, 5-bromo-6-methoxy-5,6-dihydro-3-azidothymidine-5'-(p
      bromophenyl) methoxy alaninyl phosphate (WHI-07), is a dual-function spermicidal
      and anti-HIV agent with contraceptive and microbicidal activity. In previous
      subchronic and reproductive toxicity studies and a two-year carcinogenicity
      study, daily intravaginal application of 0.5 to 2.0% WHI-07 via a gel
      microemulsion, was shown to cause no local, systemic and reproductive toxicity or
      increased carcinogenicity in mice. To evaluate the developmental toxicity
      potential of WHI-07 in a nonrodent model, subgroups of 20 superovulated NZW
      rabbits were artificially inseminated and exposed intravaginally to a gel
      microemulsion containing 0, 0.5, 1.0, or 2.0% WHI-07 during major organogenesis
      [gestation days 6-18]. The dose of WHI-07 was equivalent to 1.4x10(6) to
      5.7x10(6) times its anti-HIV IC50 and 1400 to 5700 times its spermicidal EC50.
      Throughout the duration of the experiment (GD 0-29), clinical observations, food
      consumption, and body weights were recorded. Reproductive and fetal parameters
      were evaluated following uterotomies on GD 29. Measurements included numbers of
      corpora lutea, pregnancy, number and distribution of implantations, resorptions,
      live and dead fetuses, fetal weight, sex ratio, and gross external and skeletal
      malformations and variations. Maternal food consumption and body weight gain were
      unaffected by WHI-07 treatment. Hematologic and clinical chemistry determinations
      on GD 19 and 29 revealed no treatment-related maternal effects. Prior studies of
      repeated intravaginal administration of WHI-07 gel-microemulsion revealed lack of
      local toxicity to rabbit vaginal mucosa. In the current study, no drug-related
      gross lesions were apparent at necropsy. Reproductive indices, ie, pregnancy
      rate, gravid uterine weights, litter size, number of corpora lutea, implantation
      sites, pre- and postimplantation losses, viable fetuses, resorptions, fetal body
      weights, and fetal sex ratio, were not affected by intravaginal exposure to WHI
      07. External, and skeletal examinations of fetuses for malformations and
      variations did not reveal any evidence of teratogenicity in any WHI-07-treated
      groups. Intravaginal administration of WHI-07 at concentrations as high as 2% did
      not produce teratogenicity or other developmental toxicity in rabbit conceptus.
      These findings indicated that WHI-07 shows unique clinical potential to become
      the active ingredient of a new female-controlled topical microbicidal vaginal
      contraceptive for women who are at high risk of acquiring HIV/AIDS.

PMID- 14585740
TI  - Assessment of hyperplastic lesions in rodent carcinogenicity studies.

PMID- 14585741
TI  - Reply to Gaylor. Data for high dose and low dose that do not visually fall near a
      line representing the other data.

PMID- 14585742
TI  - Rebuttal to Haseman. Calculating thresholds in animal experiments.

PMID- 14585745
TI  - Correspondence: Chromotrope 2R.

PMID- 14585743
TI  - Rebuttal to Haseman. Threshold extrapolation in chemical carcinogenesis.

PMID- 14585748
TI  - Examination of pain ratings associated with elicitation of the maximal H-wave and
      maximal M-wave in the soleus and flexor carpi radialis muscles.
AB  - The present study involved an examination of pain ratings associated with
      elicitation of the maximal H-wave and maximal M-wave in the soleus and flexor
      carpi radialis (FCR) muscles. Sixteen male students provided pain intensity
      ratings associated specifically with elicitation of the maximal H-wave and
      maximal M-wave in the soleus and FCR muscles before and after a 1 h period of
      seated rest on two trials separated by 1 wk. There were no significant
      interactions or main effects of Muscle Group, Time, or Trials for the pain
      ratings associated with the maximal H-wave and maximal M-wave in the soleus and
      FCR muscles. Pain ratings and current were higher for the maximal M-wave than the
      maximal H-wave in both the soleus and FCR muscles. We concluded that pain ratings
      associated with the maximal H-wave and maximal M-wave do not differ between the
      soleus and the FCR muscles, and that pain ratings are higher for the maximal M
      wave than the maximal H-wave.

PMID- 14585749
TI  - Task-specific motor performance and musculoskeletal response in self-classified
      right handers.
AB  - We examined the difference between the left and right hand motor performance (in
      terms of erg produced) of self-classified right handers (15 men, 15 women) for
      power (task involving muscle force) and skilled (task involving precision and eye
      hand coordination) tasks. Musculoskeletal response during task performance was
      measured by electromyogram to test the hypothesis that performance with the
      nondominant hand would trigger more generalized muscle tension. The difference
      between the left and right hand performance of men was nonsignificant for power
      task; for women, right hand performance was significantly superior than left for
      such task. Men excelled in power and women excelled in skilled tasks relative to
      their counterparts. Generalized muscle tension was significantly more during the
      left than the right hand performance for power but not for skilled tasks.

PMID- 14585751
TI  - Acalculia: an fMRI study with implications with respect to brain plasticity.
AB  - We report the case of a 44-year-old right-handed man with severe acalculia and 4
      normal age-matched controls. The acalculia patient had magnetic resonance
      findings of a wedge shaped defect in the left posterior temporal-parietal cortex,
      involving the angular gyrus, and a lacunar infarct of the right thalamus.
      Functional magnetic resonance exams were performed utilizing four tasks
      consisting of serial subtracting by sevens, basic calculation, complex
      calculation, and abstract calculation. Both patient and controls showed specific
      task-related activation with some differences that may indicate brain plasticity,
      even though no significant recovery in calculations abilities was observed in the
      patient.

PMID- 14585750
TI  - Evaluation of antioxidant status in children with acute bacterial meningitis and
      encephalitis.
AB  - Antioxidant status was investigated in children with acute bacterial meningitis
      and encephalitis to investigate the possible role of free radicals in children
      with meningitis and encephalitis. Our study included 16 children with acute
      bacterial meningitis, 13 with encephalitis, and 17 control subjects. Serum
      ceruloplasmin, uric acid, albumin, bilirubin superoxide dismutase (SOD),
      catalase, and glutathione peroxidase (GPx) levels were studied in all subjects
      within 6 h of admission. There was a statistically significant difference between
      the groups for all parameters except for serum uric acid. All antioxidant
      activities except for albumin level were increased in the study groups. Albumin
      level was higher in the control group than those of meningitis and encephalitis
      groups. When the values of meningitis and encephalitis were compared, there was a
      statistically significant difference between the groups for serum SOD, GPx,
      ceruloplasmin, and albumin. In conclusion, our study showed that serum SOD, GPx,
      catalase, and ceruloplasmin were higher in children with acute bacterial
      meningitis and serum SOD, GPx, catalase, ceruloplasmin, and total bilirubin
      levels were increased in children with encephalitis. These findings suggest that
      antioxidant status was almost similar in both acute bacterial meningitis and
      encephalitis conditions in childhood.

PMID- 14585752
TI  - Neurodegenerative effect of electrocauterization on spinal nerve root: an
      experimental study.
AB  - We investigated the number of degenerated neurons in spinal roots of rabbits
      after spinal surgery to test if electrocauterization causes neuronal loss. The
      number of degenerated neurons was higher in study group than in control group,
      and the number of live neurons was higher in control group than in study group.
      These results suggest that electrocauterization applied during spinal surgery is
      hazardous to spinal neurons and should not be applied unless required.

PMID- 14585753
TI  - A hypothalamic digoxin-mediated model for autism.
AB  - The isoprenoid pathway and its metabolites--digoxin, dolichol, and ubiquinone-
      were assessed in autism. The isoprenoid pathway and digoxin status was also
      studied for comparison in individuals of differing hemispheric dominance to
      determine the role of cerebral dominance in the genesis of autism. There was an
      upregulation of the isoprenoid pathway as evidenced by elevated HMG CoA reductase
      activity in autism. Digoxin, an endogenous Na+-K+ ATPase inhibitor secreted by
      the hypothalamus, was found to be elevated and RBC membrane Na+-K+ ATPase
      activity was found to be reduced in autism. Membrane Na+-K+ ATPase inhibition can
      result in increased intracellular Ca2+ and reduced magnesium levels. Hypothalamic
      digoxin can modulate conscious and subliminal perception and its dysfunction may
      lead to autism. Digoxin can also preferentially upregulate tryptophan transport
      over tyrosine resulting in increased levels of depolarizing tryptophan
      catabolites--serotonin, quinolinic acid (NMDA agonist), strychnine (blocks
      glycinergic inhibitory transmission), and nicotine (promotes dopamine release)
      and decreased levels of hyperpolarizing tyrosine catabolites--dopamine,
      noradrenaline, and morphine--contributing to membrane Na+-K+ ATPase inhibition.
      Increased nicotine levels can produce increased dopaminergic transmission in the
      presence of low dopamine levels. NMDA excitotoxicity could result from
      hypomagnesemia induced by membrane Na+-K+ ATPase inhibition and quinolinic acid,
      an NMDA agonist acting on the NMDA receptor. Hypomagnesemia and increased
      dolichol level can affect glycoconjugate metabolism and membranogenesis leading
      on to disordered synaptic connectivity in the limbic allocortex and defective
      presentation of viral antigens and neuronal antigens contributing to autoimmunity
      and viral persistence important in the pathogenesis. Membrane Na+-K+ ATPase
      inhibition can produce immune activation, a component of autoimmunity.
      Mitochondrial dysfunction consequent to altered calcium/magnesium ratios and
      reduced ubiquinone levels can result in increased free radical generation and
      reduced free radical scavenging and defective apoptosis leading to abnormal
      synaptogenesis. Autism can thus be considered a syndrome of hypothalamic digoxin
      hypersecretion consequent to an upregulated isoprenoid pathway. The biochemical
      patterns including hyperdigoxinemia observed in autism correlated with those
      obtained in right hemispheric chemical dominance. Right hemispheric chemical
      dominance is a predisposing factor for autism.

PMID- 14585754
TI  - Hypothalamic-mediated model for systemic lupus erythematosis: relation to
      hemispheric chemical dominance.
AB  - The isoprenoid pathway including endogenous digoxin was assessed in systemic
      lupus erythematosis (SLE). All the patients with SLE were right-handed/left
      hemispheric dominant by the dichotic listening test. This was also studied for
      comparison in patients with right hemispheric and left hemispheric dominance. The
      isoprenoid pathway was upregulated with increased digoxin synthesis in patients
      with SLE and in those with right hemispheric dominance. In this group of patients
      (i) the tryptophan catabolites were increased and the tyrosine catabolites
      reduced, (ii) the dolichol and glycoconjugate levels were elevated, (iii)
      lysosomal stability was reduced, (iv) ubiquinone levels were low and free radical
      levels increased, and (v) the membrane cholesterol:phospholipid ratios were
      increased and membrane glycoconjugates reduced. On the other hand, in patients
      with left hemispheric dominance the reverse patterns were obtained. The
      biochemical patterns obtained in SLE is similar to those obtained in left
      handed/right hemispheric chemically dominant individuals. But all the patients
      with SLE were right-handed/left hemispheric dominant by the dichotic listening
      test. Hemispheric chemical dominance has no correlation with handedness or the
      dichotic listening test. SLE occurs in right hemispheric chemically dominant
      individuals, and is a reflection of altered brain function. The role of the
      isoprenoid pathway in the pathogenesis of SLE and its relation to hemispheric
      dominance is discussed.

PMID- 14585755
TI  - Isoprenoid pathway-related membrane dysfunction in neuropsychiatric disorders.
AB  - The membrane composition and the isoprenoid pathway metabolites important in
      maintaining cell membrane integrity was studied in neurological and psychiatric
      disorders. The results indicate alteration in cholesterol:phospholipid ratio of
      the RBC membrane which is increased in glioma, schizophrenia, and bipolar mood
      disorder (MDP); decreased in multiple sclerosis and Parkinson's disease; and not
      significantly altered in epilepsy. The concentration of total glycosaminoglycans
      (GAG), hexose, and fucose decreased in the RBC membrane and increased in the
      serum. The RBC membrane Na+-K+ ATPase activity was reduced and serum HMG CoA
      reductase activity was increased. There were increased serum levels of digoxin,
      cholesterol, and dolichol and decreased levels of ubiquinone. The serum magnesium
      and tyrosine levels were reduced and tryptophan increased. The results indicate a
      defect in membrane formation and a decreased membrane Na+-K+ ATPase activity in
      all the disorders studied.  The results are discussed, and a hypothesis regarding
      the relationship between these disorders and defective membrane architecture and
      membrane Na+-K+ ATPase inhibition is presented.

PMID- 14585756
TI  - Hypothalamic digoxin, hemispheric chemical dominance, and sarcoidosis.
AB  - The isoprenoid pathway produces three key metabolites--endogenous digoxin,
      dolichol, and ubiquinone. This was assessed in patients with systemic
      sarcoidosis. All l5 patients with sarcoidosis were right-handed/left hemispheric
      dominant by the dichotic listening test. The pathway was also studied in normal
      right hemispheric, left hemispheric, and bihemispheric dominant individuals for
      comparison to find out the role of hemispheric dominance in the pathogenesis of
      sarcoidosis. In patients with sarcoidosis there was elevated digoxin synthesis,
      increased dolichol, and glycoconjugate levels, and low ubiquinone and elevated
      free radical levels. There was also an increase in tryptophan catabolites and a
      reduction in tyrosine catabolites. There was an increase in
      cholesterol:phospholipid ratio and a reduction in glycoconjugate level of RBC
      membrane in these patients. The neurotransmitter/digoxin-mediated increased intra
      cellular calcium induced immune activation, ubiquinone deficiency-related
      mitochondrial dysfunction/free radical generation, and increased dolichol-related
      altered glycoconjugate metabolism/endogenous self-glycoprotein antigen generation
      are crucial to the pathogenesis of sarcoidosis. The biochemical patterns obtained
      in sarcoidosis are similar to those obtained in left-handed/right hemispheric
      chemically dominant individuals by the dichotic listening test. But all the
      patients with sarcoidosis were right-handed/left hemispheric dominant by the
      dichotic listening test. Hemispheric chemical dominance has no correlation with
      handedness or the dichotic listening test. Sarcoidosis occurs in right
      hemispheric chemically dominant individuals and is a reflection of altered brain
      function.

PMID- 14585757
TI  - Regular developmental changes in EEG multifractal characteristics.
AB  - Electroencephalograms (EEGs) of 110 pupils (aged 6.5-19.5 years; 48 healthy
      subjects, 51 with cerebral palsy, 11 with acquired cerebral defect) were
      acquired. The stable age dependences of averaged parameters of k x f-beta EEG
      spectra model, deviations from the model, and normalized ranges of detrended EEGs
      were found. These dependences were observed in both healthy subjects and
      patients, in males and females, in the cases of congenital and acquired
      pathology. This regularity reflects the process of cerebral maturation and
      developmental change of structure types of the EEG process, and it is inherent to
      normal as well as to abnormal brain development.

PMID- 14585758
TI  - The place of birth: childbearing and kinship in Calcutta middle-class families.
AB  - Hospital births were introduced to India during the colonial period but became a
      popular option during the 1960s. Today they have replaced "traditional" home
      birth among the urban middle classes, and a significant proportion of hospital
      births are elective Caesarean sections. In this article I examine this mode of
      birth in the context of specific marital and residential patterns and cross
      generational accounts of birth among middle-class women in Calcutta. By paying
      close attention to affinal relations and the meaning of kinship for birthing
      women, I challenge assumptions regarding the positive aspects of previous, less
      medicalized, modes of birth and explore how the shift towards Caesarean sections
      does not merely signify an unquestioning acceptance of an alienating allopathic
      regime. The ethnographic accounts of different experiences of childbirth show
      that the medicalization of childbirth should be situated within the context of
      wider kin and class relations that affect women's choice and their sense of
      agency.

PMID- 14585759
TI  - Imagining HIV/AIDS: morality and perceptions of personal risk in Nigeria.
AB  - The disparity between people's knowledge about HIV/AIDS and the extent to which
      they take measures to protect themselves is one of the most vexing issues for
      public health workers and social science analysts. This paper aims to explain
      some of this discrepancy, using survey and ethnographic data collected among
      young rural-urban migrants in Aba and Kano, two cities in Nigeria. The paper
      argues that many young Nigerian migrants do not perceive significant personal
      risk because they construct the risk of AIDS in ethical and moral terms,
      projecting immorality and danger onto imaginary others. To understand the way
      young Nigerians interpret risk, the paper focuses on four related issues: (1) the
      organization and meaning of sexual relationships; (2) the intersection of gender
      and ideas about reproduction; (3) the perception of AIDS as a disease without
      hope; and (4) the importance of religion in young people's framing of moralities
      and ethical choices about sexuality and HIV/AIDS.

PMID- 14585760
TI  - Negative affect and mortality in older persons.
AB  - The authors examined the relation of negative affect to mortality in the
      Religious Orders Study, a longitudinal cohort study of older persons, between
      1994 and 2002. Participants were 851 Catholic clergy members without dementia at
      baseline (mean age, 75.4 (standard deviation, 6.9) years; 68% women). They
      completed standard measures of depressive symptoms, proneness to anxiety and
      anger, and patterns of anger expression at baseline and then underwent annual
      clinical evaluations for a mean of 4.7 (standard deviation, 2.7) years. The
      association of each scale with mortality was examined in proportional hazards
      models adjusted for age, sex, education, measures of cognitive function, lower
      limb function, chronic illness, smoking, alcohol, and obesity. During follow-up,
      164 persons died. Measures of internally experienced negative affect, such as
      depressive symptoms and suppressed anger, were related to mortality, but measures
      of externally directed negative affect, such as the tendencies to be angry with
      others and to express anger overtly, were not. Persons with a high score (90th
      percentile) on a summary measure of internally experienced negative affect were
      nearly twice as likely to die as persons with a low score (10th percentile). The
      results suggest that negative affect in older persons, especially internally
      experienced distress, is associated with an increased mortality risk.

PMID- 14585761
TI  - Effects of the hepatic lipase gene and physical activity on coronary heart
      disease risk.
AB  - There are environmental determinants and genetic susceptibility to coronary heart
      disease (CHD); however, identifying factors that modify genetic risk has been
      difficult. Evidence suggests that a common polymorphism in the hepatic lipase
      gene (LIPC-480C>T) may be related to susceptibility to CHD and that physical
      activity is a behavioral factor associated with CHD. This population-based
      prospective study in the San Luis Valley of Colorado investigated the role of the
      LIPC-480C>T polymorphism in predicting clinical CHD and the modifying effect of
      physical activity. Hispanics and non-Hispanic Whites (n = 966) were followed for
      14 years (1984-1998); 91 CHD events occurred. The LIPC-480 TT genotype predicted
      an increase in CHD in both ethnic groups, and physical activity altered this
      relation. In the full cohort, the rate of CHD was significantly elevated among
      subjects with the high-risk genotype and normal levels of physical activity
      (hazard ratio = 2.58, 95% confidence interval: 1.39, 4.77) but was not elevated
      among those with the high-risk genotype who participated in vigorous physical
      activity (hazard ratio = 0.52, 95% confidence interval: 0.12, 2.19) (reference
      group: LIPC-480 CC/CT, normal physical activity). Thus, in this prospective
      cohort study, the LIPC-480 TT genotype increased susceptibility to CHD only in
      those subjects with normal levels of physical activity, not in those with the
      high-risk genotype who were vigorously active.

PMID- 14585762
TI  - Erythrocyte sedimentation rate, an independent predictor of coronary heart
      disease in men and women: The Reykjavik Study.
AB  - The relation between erythrocyte sedimentation rate (ESR) and risk of developing
      coronary heart disease (CHD) or fatal cerebrovascular accident was assessed in a
      cohort of 7,988 men and 8,685 women who participated in The Reykjavik Study
      (Iceland). Cardiovascular risk assessment was based on characteristics at
      baseline, from 1967 to 1996. During an average follow-up of 19 and 20 years,
      2,092 men and 801 women, respectively, developed CHD, and 251 men and 178 women
      died from cerebrovascular accident. For men, the fully adjusted increase in risk
      of developing CHD predicted by the top compared with the bottom quintile of ESR
      was 57% (hazard ratio = 1.57, 95% confidence interval: 1.38, 1.78; p < 0.001);
      for women, risk was increased by 49% (hazard ratio = 1.49, 95% confidence
      interval: 1.16, 1.90; p < 0.001). The increased risk after baseline ESR
      measurement was stable for up to 25 years for men and 20 years for women. The
      fully adjusted risk of death due to stroke predicted by increasing the ln(ESR +
      1) by one standard deviation was increased by 15% for men (p = 0.06) and 16% for
      women (p = 0.08). In conclusion, ESR is a long-term independent predictor of CHD
      in both men and women. These findings support the evidence of an inflammatory
      process in atherosclerosis.

PMID- 14585763
TI  - Prospective study of selenium levels in toenails and risk of coronary heart
      disease in men.
AB  - Selenium is a trace mineral that plays a role in antioxidant defenses as a
      component of glutathione peroxidase. Epidemiologic findings on the relation of
      selenium status to risk of heart disease are inconsistent. Therefore, the authors
      investigated prospectively the association between toenail selenium levels and
      risk of coronary heart disease (CHD) in a case-control study nested within the
      Health Professionals Follow-up Study. Between 1987 and 1992, 470 CHD cases were
      newly diagnosed. A control matched to each case on age, smoking status, and date
      of toenail return was chosen. Toenail selenium levels analyzed by neutron
      activation were not associated with risk of total CHD after adjustment for age
      and smoking and other CHD risk factors (highest quintile vs. lowest: odds ratio
      (OR) = 0.86, 95% confidence interval (CI): 0.55, 1.32; p-trend = 0.75). Selenium
      level was inversely associated with risk of nonfatal myocardial infarction for
      extreme quintiles (OR = 0.54, 95% CI: 0.31, 0.93; p-trend = 0.07), was less so
      for fatal CHD (OR = 0.79, 95% CI: 0.39, 1.60; p-trend = 0.61), and was directly
      associated with coronary revascularization procedures (OR = 2.38, 95% CI: 1.11,
      5.09; p-trend = 0.02). Although these findings suggest no overall relation
      between selenium status and CHD, a specific protective role for myocardial
      infarction cannot be excluded.

PMID- 14585764
TI  - Association of a woman's own birth weight with her subsequent risk for pregnancy
      induced hypertension.
AB  - Studies have linked low birth weight to elevated risk for adult hypertension and
      insulin resistance. However, the relation between birth weight and later risk for
      pregnancy-induced hypertension (PIH), a disorder associated with insulin
      resistance and predictive of chronic hypertension, has not been well studied.
      This case-control study used linked hospital discharge and vital record data from
      New York State. Subjects were healthy women born in New York State who completed
      a first pregnancy there between 1994 and 1998. Records from each woman's own
      birth (1970-1985) were linked to those from her first pregnancy. Cases were 2,180
      women diagnosed with PIH. Controls were the 22,955 remaining women with no record
      of PIH. Birth weight showed a U-shaped relation to risk for PIH, with the highest
      risks associated with very low and very high birth weights. Relative to women
      born at 3.5-4.0 kg, odds ratios adjusted for gestational age were 2.1 (95%
      confidence interval (CI): 1.1, 3.9) and 1.6 (95% CI: 1.1, 2.4), respectively, for
      women with birth weights less than 1.5 kg and greater than 4.5 kg. Adjustment for
      other perinatal factors reduced the association with high birth weight to 1.1
      (95% CI: 0.7, 1.7) but strengthened that with lower birth weights, leaving a
      strong, inverse relation between birth weight and PIH risk (p for trend <
      0.0001). These findings support a possible role for early life factors,
      particularly fetal growth, in the etiology of PIH.

PMID- 14585765
TI  - Age dependence of the influence of methylenetetrahydrofolate reductase genotype
      on plasma homocysteine level.
AB  - An elevated plasma homocysteine level is a risk factor for cardiovascular disease
      and is often observed in other common disorders, including neural tube defects,
      pregnancy complications, and Alzheimer's disease. Plasma homocysteine level is
      affected by vitamin intake and by sequence variation in enzymes of homocysteine
      metabolism. One such enzyme, methylenetetrahydrofolate reductase (MTHFR),
      synthesizes 5-methyltetrahydrofolate, utilized in homocysteine remethylation to
      methionine. A variant of the MTHFR gene at base pair 677 is associated with
      reduced activity, increased thermolability, and hyperhomocysteinemia. This
      variant has been reported to increase risk of the aforementioned disorders.
      However, not all studies examining disease risk with respect to MTHFR genotype
      have reported a statistically significant relation. The current authors
      hypothesized that the effect of the variant might be stronger in younger age
      groups, as is the case with other genetic risk factors. Thus, the authors
      examined data from three North American studies: a study of mothers of spina
      bifida children and control mothers (1995-1996; n = 136); the National Heart,
      Lung, and Blood Institute Family Heart Study (1994-1995; n = 537); and a Mayo
      Clinic study of patients undergoing coronary angiography (1998-1999; n = 504). In
      each study, the effect of MTHFR genotype on plasma homocysteine level was
      statistically significant only in younger age groups. Failure to examine younger
      patients separately may explain why some studies have found no association
      between the genotype and cardiovascular disease.

PMID- 14585766
TI  - Modeling the time dependence of the association between human papillomavirus
      infection and cervical cancer precursor lesions.
AB  - The authors studied the time-dependent association between human papillomavirus
      (HPV) infection and squamous intraepithelial lesions (SIL) among women enrolled
      in a cohort study in Brazil (1993-2002), using repeated Papanicolaou cytologic
      examination and HPV testing by polymerase chain reaction. Through simulation with
      conceivable alternative cohort designs, they investigated different regression
      modeling approaches using time-varying covariates, time-varying hazard ratio
      functions, and repeated events to assess the effect of delay in lesion detection.
      Associations between HPV and early SIL were of high magnitude. The age-adjusted
      hazard ratios for the association between HPV at enrollment and low-grade SIL
      decreased gradually with time until 72 months for both oncogenic types of HPV
      (hazard ratio = 3.96, 95% confidence interval (CI): 2.5, 6.4) and nononcogenic
      types (hazard ratio = 2.37, 95% CI: 1.3, 4.3). The hazard ratio for incident high
      grade SIL remained constant, ranging from 7.15 (95% CI: 2.0, 25.1) at 12 months
      to 6.26 (95% CI: 2.7, 14.5) at 72 months for oncogenic types of HPV. With
      oncogenic HPV as the time-dependent predictor variable, the hazard ratios for
      incident SIL and high-grade SIL events were 14.2 (95% CI: 8.7, 23.1) and 32.7
      (95% CI: 8.4, 127.3), respectively. Investigators may underestimate the
      prognostic value of HPV detection using designs that rely on HPV ascertainment at
      a single time point. The waning in hazard ratios should be considered in the
      implementation of HPV testing-based screening programs.

PMID- 14585767
TI  - Tuberculosis in household contacts of infectious cases in Kampala, Uganda.
AB  - Tuberculosis remains a serious threat to public health, especially in sub-Saharan
      Africa. To determine the host and environmental factors responsible for
      tuberculosis in African households, the authors performed a prospective cohort
      study of 1,206 household contacts of 302 index cases with tuberculosis enrolled
      in Uganda between 1995 and 1999. All contacts were systematically evaluated for
      active tuberculosis and risk factors for active disease. Among the 1,206
      household contacts, 76 secondary cases (6%) of tuberculosis were identified. Of
      these cases, 51 were identified in the baseline evaluation, and 25 developed
      during follow-up. Compared with index cases, secondary cases presented more often
      with minimal disease. The risk for secondary tuberculosis was greater among young
      children than adults (10% vs. 1.9%) and among human immunodeficiency virus
      seropositive than -seronegative contacts (23% vs. 3.3%). Host risk factors could
      not be completely separated from the effects of environmental risk factors,
      suggesting that a household may represent a complex system of interacting risks
      for tuberculosis.

PMID- 14585768
TI  - Sample size needed to detect gene-gene interactions using association designs.
AB  - It is likely that many complex diseases result from interactions among several
      genes, as well as environmental factors. The presence of such interactions poses
      challenges to investigators in identifying susceptibility genes, understanding
      biologic pathways, and predicting and controlling disease risks. Recently,
      Gauderman (Am J Epidemiol 2002;155:478-84) reported results from the first
      systematic analysis of the statistical power needed to detect gene-gene
      interactions in association studies. However, Gauderman used different
      statistical models to model disease risks for different study designs, and he
      assumed a very low disease prevalence to make different models more comparable.
      In this article, assuming a logistic model for disease risk for different study
      designs, the authors investigate the power of population-based and family-based
      association designs to detect gene-gene interactions for common diseases. The
      results indicate that population-based designs are more powerful than family
      based designs for detecting gene-gene interactions when disease prevalence in the
      study population is moderate.

PMID- 14585769
TI  - Evaluating medication effects outside of clinical trials: new-user designs.
AB  - Recent clinical trials demonstrating that hormone replacement therapy (HRT) does
      not prevent coronary heart disease in women have again raised doubts concerning
      observational studies. Although much of the explanation probably lies in what
      might be called the "healthy HRT user" effect, another contributing factor may be
      that most observational studies included many prevalent users: women taking HRT
      for some time before study follow-up began. This practice can cause two types of
      bias, both of which plausibly may have contributed to the discrepancy between
      observational and randomized studies. First, prevalent users are "survivors" of
      the early period of pharmacotherapy, which can introduce substantial bias if risk
      varies with time, just as in studies of operative procedures that enroll patients
      after they have survived surgery. This article provides several examples of
      medications for which the hazard function varies with time and thus would be
      subject to prevalent user bias. Second, covariates for drug users at study entry
      often are plausibly affected by the drug itself. Investigators often do not
      adjust for these factors on the causal pathway, which may introduce confounding.
      A new-user design eliminates these biases by restricting the analysis to persons
      under observation at the start of the current course of treatment. This article
      thus argues that such designs should be used more frequently in
      pharmacoepidemiology.

PMID- 14585770
TI  - Evaluation of cluster randomized controlled trials in sub-Saharan Africa.
AB  - Cluster randomized controlled trials (CRCTs) are attractive in settings in which
      individual randomization is difficult or impossible. This issue is common when
      studying several health problems in developing countries. The authors aimed to
      assess empirically the extent to which the prerequisite design and analysis
      aspects of cluster randomization were taken into account and reported properly in
      CRCTs conducted in sub-Saharan Africa. CRCTs published in the last three decades
      were evaluated by using a checklist based on the Consolidated Standards of
      Reporting Trials (CONSORT) statement. The authors identified 51 eligible CRCTs;
      40 of them (78%) had been published after 1990. Only 10 (20%) studies took
      clustering into account in sample size or power calculations, and only 19 (37%)
      took clustering into account in the analysis. Intracluster correlation
      coefficients and design effects were reported in only one (2%) and three (6%)
      trials, respectively. An increasing number of CRCTs are conducted in sub-Saharan
      Africa, but many are not analyzed and reported properly. The special features
      stemming from cluster randomization need to be addressed in the design, analysis,
      and reporting of these studies.

PMID- 14585772
TI  - Re: "Genital human papillomavirus infection: incidence and risk factors in a
      cohort of female university students".

PMID- 14585773
TI  - Re: "Electromagnetic fields, polychlorinated biphenyls, and prostate cancer
      mortality in electric utility workers".

PMID- 14585775
TI  - The art of evidence-based child psychiatry.

PMID- 14585776
TI  - Bipolar disorder.

PMID- 14585777
TI  - Depression in children and adolescents.

PMID- 14585778
TI  - Prodromal symptoms may be identified by people with bipolar or unipolar
      depression.

PMID- 14585779
TI  - Risk of suicide remains high fifteen years after deliberate self-harm.

PMID- 14585780
TI  - Expected levels of behaviour problems in a population sample of children between
      four and eighteen years.

PMID- 14585781
TI  - Insufficient evidence on benefits of early detection and treatment of dementia.

PMID- 14585782
TI  - Nurse administered structured clinical interviews improve psychiatric diagnosis
      and treatment in community settings.

PMID- 14585783
TI  - Rofecoxib or naproxen do not slow progression of mild to moderate Alzheimer's
      disease.

PMID- 14585784
TI  - Oestrogen plus progestin doubles the risk of dementia in post-menopausal women.

PMID- 14585786
TI  - Review: the case for antidepressants for treating depression in people with
      schizophrenia remains unproven.

PMID- 14585785
TI  - Targeted cognitive behavioural therapy may reduce relapse in people with
      prodromal symptoms of schizophrenia.

PMID- 14585787
TI  - Family focused psychoeducational therapy decreases relapse and rehospitalisation
      in people with a manic episode and bipolar disorder.

PMID- 14585788
TI  - Group psychoeducation reduces recurrence and hospital admission in people with
      bipolar disorder.

PMID- 14585789
TI  - Collaborative care speeds recovery from depression.

PMID- 14585790
TI  - Review: selective serotonin reuptake inhibitors as effective as tricyclic
      antidepressants for major depression, and may have fewer adverse effects.

PMID- 14585792
TI  - Gradual reduction of benzodiazepines, with or without cognitive behavioural
      therapy, increases successful withdrawal rates compared with no support in long
      term users.

PMID- 14585791
TI  - Review: repetitive transcranial magnetic stimulation is of unknown effectiveness
      in people with depression.

PMID- 14585793
TI  - Helping parents solve stressful life problems enhances the effectiveness of
      interventions for child aggression and antisocial behaviour.

PMID- 14585794
TI  - Review: evidence is lacking about suicide prevention in young people.

PMID- 14585795
TI  - Review: therapeutic relationship is modestly correlated with treatment outcome in
      child and adolescent psychotherapy.

PMID- 14585796
TI  - Behavioural family counselling reduces drug use in opioid-dependent men.

PMID- 14585797
TI  - Trauma-focused group psychotherapy is not effective for posttraumatic stress
      disorder in Vietnam veterans.

PMID- 14585799
TI  - Review: stress is a problem for mental health nurses but research on
      interventions is insufficient.

PMID- 14585798
TI  - Self-help manuals may reduce bingeing and purging in bulimia nervosa.

PMID- 14585800
TI  - Counselling may be more expensive than usual care for people with mental health
      problems, but may not be more effective for improving Beck depression score in
      the long term.

PMID- 14585801
TI  - Stigma alone does not explain non-disclosure of psychological symptoms in general
      practice.

PMID- 14585802
TI  - Mechanisms underlying the inhibitory effects of tachykinin receptor antagonists
      on eosinophil recruitment in an allergic pleurisy model in mice.
AB  - The activation of tachykinin NK receptors by neuropeptides may induce the
      recruitment of eosinophils in vivo. The aim of the present study was to
      investigate the effects and underlying mechanism(s) of the action of tachykinin
      receptor antagonists on eosinophil recruitment in a model of allergic pleurisy in
      mice. Pretreatment of immunized mice with capsaicin partially prevented the
      recruitment of eosinophils after antigen challenge, suggesting the potential
      contribution of sensory nerves for the recruitment of eosinophils Local (10-50
      nmol per pleural cavity) or systemic (100-300 nmol per animal) pretreatment with
      the tachykinin NK1 receptor antagonist SR140333 prevented the recruitment of
      eosinophils induced by antigen challenge of immunized mice. Neither tachykinin
      NK2 nor NK3 receptor antagonists suppressed eosinophil recruitment. Pretreatment
      with SR140333 failed to prevent the antigen-induced increase of interleukin-5
      concentrations in the pleural cavity. Similarly, SR140333 failed to affect the
      bone marrow eosinophilia observed at 48 h after antigen challenge of immunized
      mice. SR140333 induced a significant increase in the concentrations of antigen
      induced eotaxin at 6 h after challenge. Antigen challenge of immunized mice
      induced a significant increase of Leucotriene B4 (LTB4) concentrations at 6 h
      after challenge. Pretreatment with SR140333 prevented the antigen-induced
      increase of LTB4 concentrations. Our data suggest an important role for NK1
      receptor activation with consequent LTB4 release and eosinophil recruitment in a
      model of allergic pleurisy in the mouse. Tachykinins appear to be released mainly
      from peripheral endings of capsaicin-sensitive sensory neurons and may act on
      mast cells to facilitate antigen-driven release of LTB4.

PMID- 14585803
TI  - Impaired host defense to Klebsiella pneumoniae infection in mice treated with the
      PDE4 inhibitor rolipram.
AB  - The increase in levels of cAMP in leukocytes by selective inhibitors of PDE4 may
      result in reduction of inflammation, and may be useful in the treatment of
      pulmonary inflammatory disorders in humans. Here, we have assessed whether oral
      treatment with the prototype PDE4 inhibitor, rolipram, interfered with the
      antibacterial host response following pulmonary infection of mice with Klebsiella
      pneumoniae. K. pneumoniae infection induced a marked increase in the recruitment
      of neutrophils to the lungs and the production of proinflammatory cytokines and
      chemokines, including tumor necrosis factor-alpha (TNF-alpha) and keratinocyte
      derived chemokine (KC), in bronchoalveolar (BAL) fluid and lung tissue. There
      were also detectable amounts of interleukin-10 (IL-10) and significant lethality.
      Treatment with rolipram (3-30 mg kg-1) was associated with earlier lethality and
      significant inhibition of the TNF-alpha production. This was associated with
      enhanced production of IL-10 in lung tissue of rolipram-treated animals. Rolipram
      treatment did not affect KC expression and the recruitment of neutrophils in the
      lung tissue. Over 70% of neutrophils that migrated into the BAL fluid following
      K. pneumoniae infection ingested bacteria. Treatment with rolipram inhibited the
      percentage of neutrophils undergoing phagocytosis of K. pneumoniae in a dose
      dependent manner. Maximal inhibition (62%) occurred at doses equal to or greater
      than 10 mg kg-1. Thus, treatment of mice with the PDE4 inhibitor rolipram is
      accompanied by earlier lethality, enhanced bacterial load and decreased capacity
      of the responding host to produce TNF-alpha and of neutrophils to phagocytose
      bacteria. It will be important to investigate whether the shown ability of PDE4
      inhibitors to inhibit neutrophil phagocytosis and control experimental bacterial
      infection will translate into an inhibition of the ability of neutrophils to deal
      with infectious microorganisms in the clinical setting.

PMID- 14585805
TI  - The escape of the mink embryo from obligate diapause.
AB  - The obligate embryonic diapause that characterizes gestation in mink engenders a
      developmental arrest at the blastocyst stage. The characteristics of escape from
      obligate diapause were investigated in embryos reactivated by treatment of the
      dams with exogenous prolactin. Protein and DNA synthesis showed marked increases
      within 72 h after the reinitiation of development, and embryo diameter increased
      thereafter. Trophoblast cells from embryos at Day 5 after activation proliferated
      more readily in vitro than trophoblasts from diapause or from Day 9 after
      activation, while in Day 9 embryos, cells from the inner cell mass (ICM)
      replicated comparatively more readily in vitro. There was evidence of expression
      of fibroblast growth factor-4 (FGF4) in both diapause and activated embryos and
      in ICM, but not the trophoblast. FGF receptor-2 was present in embryos from Day 5
      after reactivation in both trophoblast and ICM cell lines. Trophoblast cell lines
      established from mink embryos proliferated in culture in the presence of FGF4
      with a doubling time of 1.4 days, while in its absence, the doubling time was 4.0
      days. We conclude that, during reinitiation of embryogenesis in the mink after
      diapause, embryo growth is characterized by gradual increases in protein
      synthesis, accompanied by mitosis of the trophoblast and ICM. There appears to be
      a pattern of differential proliferation between cells derived from these
      embryonic compartments, with the trophoblast phase of replication occurring
      mainly in the early reactivation phase, while the ICM proliferates more rapidly
      nearer to the time of implantation.

PMID- 14585807
TI  - Growth differentiation factor-9 and stem cell factor promote primordial follicle
      formation in the hamster: modulation by follicle-stimulating hormone.
AB  - Growth differentiation factor-9 (GDF-9) and stem cell factor (SCF) influence
      follicle formation beyond the primary stage; however, factors influencing the
      formation of primordial follicles remain elusive. To determine whether GDF-9 and
      SCF promoted primordial follicle formation during ovarian morphogenesis in the
      hamster, and whether FSH had any modulatory influence, fetal ovaries were
      collected on Gestation Day 15 from pregnant hamsters treated with or without an
      FSH antiserum on Gestation Day 12 and cultured in vitro up to Day 9 with SCF, GDF
      9, or FSH. The percentages and diameters of primordial, primary, and secondary
      follicles and their oocytes were determined by morphometric evaluation, and the
      expression of GDF-9 was detected by immunolocalization. SCF, GDF-9, and FSH
      promoted primordial and primary follicle formation, but GDF-9 was more efficient.
      The diameters of the follicles developed under GDF-9 or FSH, but not SCF,
      compared well with those developed in vivo. FSH- and GDF-9-induced
      folliculogenesis was attenuated by the SCF antibody. Similarly, in vitro
      formation of primordial follicles decreased markedly in ovaries exposed to the
      FSH antiserum in utero, which was reversed by SCF, GDF-9, or FSH; however, GDF-9
      had a profound effect on follicular development. GDF-9 protein appeared
      exclusively in the oocytes on Postnatal Day 4; however, it appeared in vitro by
      48 h, and the expression was upregulated by FSH. These results suggest that
      although SCF-induced primordial follicle formation constitutes primarily somatic
      cell development, GDF-9 influences both the oocyte and its companion somatic
      cells. FSH plays an important role in primordial folliculogenesis in the hamster
      via GDF-9 and SCF.

PMID- 14585806
TI  - Effects of immunization against bone morphogenetic protein 15 and growth
      differentiation factor 9 on ovulation rate, fertilization, and pregnancy in ewes.
AB  - Immunization of ewes against growth differentiation factor 9 (GDF9) or bone
      morphogenetic protein 15 (BMP15) can lead to an increased ovulation rate;
      however, it is not known whether normal pregnancies occur following such
      treatments. The aims of the present study were to determine the effects of a
      short-term immunization regimen against BMP15 and GDF9 on ovulation rate,
      fertilization of released oocytes, the ability of fertilized oocytes to undergo
      normal fetal development, and the ability of immunized ewes to carry a pregnancy
      to term. Ewes were given a primary and booster immunization against keyhole
      limpet hemocyanin (KLH; control, n = 50), a GDF9-specific peptide conjugated to
      KLH (GDF9, n = 30), or a BMP15-specific peptide conjugated to KLH (BMP15, n =
      30). The estrous cycles of all ewes were synchronized, and ewes were joined with
      fertile rams approximately 14 days after the booster immunization. The number of
      corpora lutea was determined by laparoscopy 3-4 days following mating.
      Subsequently, about one-half of the ewes in each group underwent an embryo
      transfer procedure 4-6 days following mating, with the embryos being transferred
      to synchronized, nonimmunized recipients. The remaining ewes were allowed to
      carry their pregnancies to term. Short-term immunization against either BMP15 or
      GDF9 peptides resulted in an increase in ovulation rate with no apparent
      detrimental affects on fertilization of released oocytes, the ability of
      fertilized oocytes to undergo normal fetal development, or the ability of the
      immunized ewes to carry a pregnancy to term. Therefore, regulation of BMP15,
      GDF9, or both is potentially a new technique to enhance fecundity in some
      mammals.

PMID- 14585808
TI  - Isolation and characterization of gelatin-binding bison seminal vesicle secretory
      proteins.
AB  - Bovine seminal plasma (BSP) contains a family of major proteins designated BSP
      A1/A2, BSP-A3, and BSP-30kDa (collectively called BSP proteins) that bind to
      sperm at ejaculation and potentiate sperm capacitation. Homologous proteins have
      been identified in stallion, boar, goat, and ram seminal plasma. We report here
      the isolation and characterization of homologous proteins from bison seminal
      vesicle secretions. Seminal vesicle secretory proteins were precipitated by
      adding cold ethanol and recovered by centrifugation. The precipitates were
      resuspended in ammonium bicarbonate, dialyzed, and lyophilized. Lyophilized
      proteins were dissolved in 0.05 M phosphate buffer (PB) and loaded onto a gelatin
      agarose column. The unadsorbed proteins and adsorbed proteins were eluted with PB
      and 5 M urea in PB, respectively. The gelatin-adsorbed fraction was analyzed by
      SDS-PAGE and revealed the presence of four major proteins designated BiSV-16kDa,
      BiSV-17kDa, BiSV-18kDa, and BiSV-28kDa (BiSV: bison seminal vesicle proteins).
      Heparin-Sepharose chromatography allowed the separation of BiSV-16kDa, which did
      not bind heparin from other BiSV proteins, which bound heparin. Immunoblotting
      revealed that BiSV-16kDa cross-reacted with BSP-A3 antibodies, BiSV-17kDa and
      BiSV-18kDa cross-reacted with BSP-A1/-A2 antibodies, and BiSV-28kDa cross-reacted
      with BSP-30kDa antibodies. Radioimmunoassays indicated that approximately 25% of
      bison seminal vesicle total proteins are related to BSP proteins. The amino
      terminal sequencing indicated that BiSV proteins share almost 100% sequence
      identity with BSP proteins. In addition, BiSV proteins bind to low-density
      lipoproteins isolated from hen's egg yolk. These results confirm that BSP protein
      homologs are present in mammalian seminal plasma and they may share the same
      biological role.

PMID- 14585809
TI  - Paternally transmitted chromosomal aberrations in mouse zygotes determine their
      embryonic fate.
AB  - The developmental consequences of chromosomal aberrations in embryos include
      spontaneous abortions, morphological defects, inborn abnormalities, and
      genetic/chromosomal diseases. Six germ-cell mutagens with different modes of
      action and spermatogenic stage sensitivities were used to investigate the
      relationship between the types of cytogenetic damage in zygotes with their
      subsequent risk of postimplantation death and of birth as a translocation
      carrier. Independent of the mutagen used, over 98% of paternally transmitted
      aberrations were chromosome type, rather than chromatid type, indicating that
      they were formed during the period between exposure of male germ cells and
      initiation of the first S phase after fertilization. There were consistent one-to
      one agreements between the proportions of a) zygotes with unstable aberrations
      and the frequencies of dead embryos after implantation (slope = 0.87, confidence
      interval [CI]: 0.74, 1.16) and b) zygotes with reciprocal translocations and the
      frequency of translocation carriers at birth (slope = 0.74, CI: 0.48, 2.11).
      These findings suggest that chromosomal aberrations in zygotes are highly
      predictive of subsequent abnormal embryonic development and that development
      appears to proceed to implantation regardless of the presence of chromosomal
      abnormalities. Our findings support the hypothesis that, for paternally
      transmitted chromosomal aberrations, the fate of the embryo is already set by the
      end of G1 of the first cell cycle of development.

PMID- 14585810
TI  - Luteinizing hormone and follicle-stimulating hormone exhibit different secretion
      patterns from cultured Madin-Darby canine kidney cells.
AB  - LH, FSH, and chorionic gonadotropin (CG) are comprised of a common alpha subunit
      and a hormone-specific beta subunit. Using Madin-Darby canine kidney (MDCK)
      epithelial cells to examine the polarized secretion of human CG/LH, we previously
      reported that CG and LH were detected in the apical and basolateral compartments,
      respectively, and the carboxyl terminal end of the CGbeta subunit contains a
      strong apical signal. Here we show that the carboxyl seven amino acids in the
      LHbeta subunit contribute to the basolateral secretion of LH, and an LH chimera
      bearing the CGbeta apical signal is redirected from the basolateral to the apical
      compartments. Because LH and FSH are synthesized in the same cell, we also
      compared the secretion polarity of LH with FSH. MDCK cells expressing the FSH
      dimer displayed an almost equal distribution of protein into the apical and
      basolateral compartments. Given that the LHbeta and CGbeta carboxy terminal
      sequences, which differ from that in the FSHbeta subunit, occupy a pivotal role
      in their polarized behavior, the results support the hypothesis that pituitary
      exit of LH and FSH occur via different secretion pathways, and are released
      spatially from the pituitary via different circulatory routes.

PMID- 14585811
TI  - Development of leydig cells in the insulin-like growth factor-I (igf-I) knockout
      mouse: effects of igf-I replacement and gonadotropic stimulation.
AB  - Targeted gene deletion of insulin-like growth factor-I (IGF-I) results in
      diminished numbers of Leydig cells (LCs) and lower circulating testosterone (T)
      levels in adult males. The impact of endogenous IGF-I withdrawal on proliferation
      (labeling index, LI) and differentiation of LCs was investigated, testing for
      restorative effects of IGF-I replacement and/or LH stimulation. With IGF-I
      replacement in mutant mice, LIs increased more than 200% (P < 0.05). LC numbers
      were also increased by 200%, whereas the numbers of intermediate cell progenitors
      (PLCs) were unchanged compared to mutant vehicle controls. LIs of PLCs in wild
      type males increased by 200% after LH stimulation, and LC numbers increased by
      50% compared to vehicle-treated controls (P < 0.05). In contrast, there was no
      effect of LH on LI in mutant mice, but LC numbers still increased by 30% (P <
      0.05). Additive effects on LI and cell numbers were observed in response to IGF-I
      plus LH in mutants, implying that the two hormones use separate signaling
      pathways. Serum T and LH levels in wild-type and mutant males were equivalent.
      Exogenous LH increased T production 8-fold in wild-type males (P < 0.01). In
      mutant mice, neither LH stimulation nor IGF-I alone affected serum T levels, but
      IGF-I plus LH stimulation increased serum T 2-fold (P < 0.05). These data support
      the conclusions that 1) IGF-I is a critical autocrine and/or paracrine factor in
      the control of adult LC numbers and function; and 2) LH is not a direct mitogenic
      factor for LCs, and acts in part through IGF-I to stimulate proliferative
      activity.

PMID- 14585812
TI  - Testis tissue explant culture supports survival and proliferation of bovine
      spermatogonial stem cells.
AB  - The present study was designed to evaluate the survival and proliferation of
      bovine spermatogonial stem cells in an explant culture system over a 2-wk period.
      Explants of calf testicular parenchyma were placed on 0.45-microm pore membranes
      in culture and maintained for 1-2 wk. Histological examinations of fresh (t0) and
      cultured tissues revealed morphologically normal seminiferous tubules. Germ cell
      numbers/tubule increased (P < or = 0.05) during culture when compared with t0,
      yet germ cell differentiation was not observed. Testosterone was present in
      medium throughout the culture period, indicating functional Leydig cells.
      Sertoli, spermatogonial, and spermatogonial stem cell viability was evaluated by
      reverse transcription-polymerase chain reaction for cell-specific gene expression
      of stem cell factor, protein gene product 9.5, and glial cell line-derived
      neurotrophic factor family receptor-alpha1, respectively. Results demonstrated
      the expression of all genes at t0, 1 wk, and 2 wk of culture. Single-cell
      suspensions were prepared from the testicular tissues at t0 and during culture
      and transplanted into nude mouse testes to investigate spermatogonial stem cell
      viability. One month after transplantation, colonies of round bovine cells were
      identified in all mouse testes analyzed, indicating survival of spermatogonial
      stem cells. The average number of resulting colonies in recipient testes was
      significantly (P < or = 0.05) higher following 1 wk of culture compared with t0
      and was numerically higher at 2 wk of culture compared with t0. This increase in
      colony numbers over time in culture indicates spermatogonial stem cell
      proliferation in vitro. This explant culture system appears to provide an
      environment that supports survival and proliferation of bovine spermatogonial
      stem cells.

PMID- 14585813
TI  - Expression of nucleolar-related proteins in porcine preimplantation embryos
      produced in vivo and in vitro.
AB  - The expression of nucleolar-related proteins was studied as an indirect marker of
      the ribosomal RNA (rRNA) gene activation in porcine embryos up to the blastocyst
      stage produced in vivo and in vitro. A group of the in vivo-developed embryos
      were cultured with alpha-amanitin to block the de novo embryonic mRNA
      transcription. Localization of proteins involved in the rRNA transcription
      (upstream binding factor [UBF], topoisomerase I, RNA polymerase I [RNA Pol I],
      and the RNA Pol I-associated factor PAF53) and processing (fibrillarin,
      nucleophosmin, and nucleolin) was assessed by immunocytochemistry and confocal
      laser-scanning microscopy, and mRNA expression was determined by semiquantitative
      reverse transcription-polymerase chain reaction (RT-PCR). These findings were
      correlated with ultrastructural data and autoradiography following 20-min
      [3H]uridine incubation. Additionally, expression of the pocket proteins pRb and
      p130, which are involved in cell-cycle regulation, was assessed by
      semiquantitative RT-PCR up to the blastocyst stage. Toward the end of third cell
      cycle, the nuclei in non-alpha-amanitin-treated, in vivo-produced embryos
      displayed different stages of transformation of the nuclear precursor bodies
      (NPBs) into fibrillogranular nucleoli associated with autoradiographic labeling.
      However, on culture with alpha-amanitin, NPBs were not transformed into a
      fibrillogranular nucleolus during this cell cycle, demonstrating that embryonic
      nucleogenesis requires de novo mRNA transcription. Moreover, immunolocalization
      of RNA Pol I, but not of UBF, and the mRNA expression of PAF53 and UBF were
      significantly reduced or absent after culture with alpha-amanitin, indicating
      that RNA Pol I, PAF53, and presumably, UBF are derived from de novo embryonic
      transcription. Embryonic genomic activation was delayed in porcine embryos
      produced in vitro compared to the in vivo-derived counterparts with respect to
      mRNAs encoding PAF53 and UBF. Moreover, differences existed in the mRNA
      expression patterns of pRb between in vivo- and in vitro-developed embryos. These
      findings show, to our knowledge for the first time, a nucleolus-related gene
      expression in the preimplantation porcine embryo, and they highlight the
      differences in quality between in vivo and in vitro-produced embryos.

PMID- 14585814
TI  - Mullerian-inhibiting substance inhibits rat Leydig cell regeneration after
      ethylene dimethanesulphonate ablation.
AB  - The postnatal development of Leydig cell precursors is postulated to be
      controlled by Sertoli cell secreted factors, which may have a determinative
      influence on Leydig cell number and function in sexually mature animals. One such
      hormone, Mullerian inhibiting substance (MIS), has been shown to inhibit DNA
      synthesis and steroidogenesis in primary Leydig cells and Leydig cell tumor
      lines. To further delineate the effects of MIS on Leydig cell proliferation and
      steroidogenesis, we employed the established ethylene dimethanesulphonate (EDS)
      model of Leydig cell regeneration. Following EDS ablation of differentiated
      Leydig cells in young adult rats, recombinant MIS or vehicle was delivered by
      intratesticular injection for 4 days (Days 11-14 after EDS). On Days 15 and 35
      after EDS (1 and 21 days post-MIS injections), endocrine function was assessed
      and testes were collected for stereology, immunohistochemistry, and assessment of
      proliferation and steroidogenesis. Although serum testosterone and luteinizing
      hormone (LH) were no different, intratesticular testosterone was higher on Day 35
      in MIS-treated animals. At both time points, intratesticular 5alpha-androstan
      3alpha,17beta-diol concentrations were much higher than that of testosterone. MIS
      treated animals had fewer mesenchymal precursors on Day 15 and fewer
      differentiated Leydig cells on Day 35 with decreased numbers of BrdU+ nuclei.
      Apoptotic interstitial cells were observed only in the MIS-treated testes, not in
      the vehicle-treated group on Day 15. These data suggest that MIS inhibits
      regeneration of Leydig cells in EDS-treated rats by enhancing apoptotic cell
      death as well as by decreasing proliferative capacity.

PMID- 14585815
TI  - Regulation of myometrial phospholipase C system and uterine contraction by beta
      adrenergic receptors in midpregnant rat.
AB  - We investigated whether beta-adrenergic receptors (beta-AR) regulate the
      phospholipase C (PLC) system in midpregnant rat myometrium. PLCbeta isoforms were
      characterized, and the effect of isoproterenol (beta-adrenergic agonist) was
      tested on myometrial inositol phosphate (InsP) production and uterine
      contraction. Using specific antibodies, we showed that rat myometrium expresses
      PLCbeta1, PLCbeta3, and PLCbeta4, and to a lesser degree PLCbeta2. Quantitative
      analysis revealed that PLCbeta isoforms are differentially expressed during
      pregnancy. Indeed, the amount of PLCbeta4 is increased at midpregnancy, whereas
      PLCbeta1, PLCbeta2, and PLCbeta3 are up-regulated at term. At midpregnancy,
      pretreatment of myometrial strips with isoproterenol significantly reduced basal
      and agonist-stimulated InsP production. Forskolin, a diterpene that increases
      cAMP accumulation by directly activating adenylyl cyclases, had no effect on InsP
      production. In contrast, two global potassium (K+) channel inhibitors,
      tetraethylammonium (TEA) and 4-aminopyridine (4-AP), prevented attenuation of
      InsP production by isoproterenol. Isoproterenol also significantly decreased
      spontaneous and agonist-induced contraction of the longitudinal layer of
      midpregnant rat myometrium. Preincubation of uterine strips with TEA plus 4-AP
      prior to beta-AR activation blocked only partial uterine relaxation, whereas
      Forskolin was as potent as isoproterenol. This indicates that beta-AR operate
      through both K+ channels and cAMP to induce uterine relaxation. In conclusion, we
      show for the first time that three myometrial PLCbeta isoforms (PLCbeta1,
      PLCbeta2, and PLCbeta3) are down-regulated at midpregnancy. At this period, beta
      AR reduce basal and agonist-stimulated InsP production through activation of K+
      channels. Altogether, these mechanisms could act to decrease responsiveness of
      the longitudinal layer of myometrium to contractant factors.

PMID- 14585817
TI  - Sequential gonadotropin treatment of immature mice leads to amplification of
      transforming growth factor beta action, via upregulation of receptor-type 1, Smad
      2 and 4, and downregulation of Smad 6.
AB  - The present study was designed to establish the cellular localization and
      expression of transforming growth factor beta (TGFbeta) signaling pathway
      components, including TGFbeta1 and beta2; TGFbeta receptors type I (TbetaRI) and
      II (TbetaRII); and Smads 2, 3, 4, and 6 during gonadotropin-induced follicular
      maturation and ovulation in the mouse ovary. Immature 21-day-old mice were
      sequentially treated with recombinant human FSH, 5 IU daily for 3 days, and hCG
      once at Day 24 of life. Immunohistochemical experiments revealed a TGFbeta1
      staining in granulosa cells (GC) and theca interna cells (TIC) as well as in
      oocytes, whereas that of TGFbeta2 was mainly localized in oocytes and GC. Strong
      immunostaining for both TbetaRI and -RII was observed in the TIC and, to a lesser
      extent, in GC. Whereas oocytes did not exhibit any staining for TbetaRII, their
      TbetaRI immunostaining was strong. Smads were detected in oocytes, GC, and luteal
      cells and in a lesser amount in TIC; the immunostaining for Smad 4 was the
      strongest. Western blotting and reverse transcription-polymerase chain reaction
      analyses indicated that, in response to gonadotropins, TGFbeta2, TbetaRI, Smad 2
      and Smad 4 mRNA and protein levels increased, while those of Smad 6 decreased in
      ovarian homogenates. In conclusion, these results show that, in a model of
      immature mouse exposed to a sequential gonadotropin treatment, FSH and LH
      increased the expression of the TGFbeta signaling system through the increase of
      TGFbeta2, TbetaRI, stimulatory Smad 2, and common Smad 4 expression, which
      occurred concomitantly with a decrease of the inhibitory Smad 6 expression.

PMID- 14585816
TI  - Tsga10 encodes a 65-kilodalton protein that is processed to the 27-kilodalton
      fibrous sheath protein.
AB  - We had previously reported the isolation of the testis-specific human gene
      Tsga10, which is not expressed in testes from two infertile patients. To study
      its role and function, we cloned the mouse homologue Mtsga10. Mtsga10 localizes
      to mouse chromosome 1, band B. This region is syntenic with human chromosome
      2q11.2, where Tsga10 is located. We demonstrate that Mtsga10 mRNA is expressed in
      testis, but not in other adult tissues, and in several human fetal tissues and
      primary tumors. We uncovered that different species use different first exons
      and, consequently, different promoters. Using several antibodies, we discovered
      that, in mouse testis, Mtsga10 encodes a 65-kDa spermatid protein that appears to
      be processed to a 27-kDa protein of the fibrous sheath, a major sperm tail
      structure, in mature spermatozoa. Mtsga10 protein contains a putative
      myosin/Ezrin/radixin/moesin (ERM) domain. Transfection of fibroblasts with GFP
      Mtsga10 fusion protein results in formation of short, thick filaments and
      deletion of the myosin/ERM domain abolished filament formation. Our results
      suggest the possibility that Tsga10 plays a role in the sperm tail fibrous
      sheath.

PMID- 14585818
TI  - Localization and developmental expression of the activin signal transduction
      proteins Smads 2, 3, and 4 in the baboon fetal ovary.
AB  - We recently demonstrated that the reduction in the number of primordial follicles
      in ovaries of near-term baboon fetuses deprived of estrogen in utero was
      associated with increased expression of alpha-inhibin, but not activin betaA and
      betaB or the activin receptors. Therefore, we proposed that estrogen regulates
      fetal ovarian follicular development by controlling the intraovarian
      inhibin:activin ratio. As a prelude to conducting experiments to test this
      hypothesis, in the current study we determined whether the primate fetal ovary
      expressed Smads 2/3 and 4 and whether expression of these activin-signaling
      proteins was altered in fetal ovaries of baboons in which estrogen production was
      suppressed. Western blot analyses demonstrated that the 59 kDa Smad 2, 54 kDa
      Smad 3, and 64 kDa Smad 4 proteins were expressed in fetal ovaries of untreated
      baboons at both mid and late gestation and that the level of expression was not
      significantly altered in late gestation by in vivo treatment with CGS 20267 or
      CGS 20267 and estrogen. Immunocytochemistry localized Smads 2/3 and 4 to
      cytoplasm of oocytes and pregranulosa cells at midgestation and oocytes and
      granulosa cells of primordial follicles in late gestation. Smad 4 was also
      detected in granulosa cell nuclei in late gestation, and nuclear expression
      appeared to be decreased in fetal ovaries of baboons deprived of estrogen. The
      site of localization of Smads correlated with localization of the activin
      receptors IA and IIB, which we previously showed were abundantly expressed in
      oocytes and (pre)granulosa cells at both mid and late gestation and unaltered by
      estrogen deprivation. In summary, the results of the current study are the first
      to show that the intracellular signaling molecules required to transduce an
      activin signal are expressed in the baboon fetal ovary and that expression was
      not altered by estrogen deprivation in utero. These findings, coupled with our
      previous observations showing that estrogen deprivation reduced follicle numbers
      and upregulated/induced expression of inhibin but not activin or the activin
      receptors, lend further support to the hypothesis that estrogen regulates fetal
      ovarian folliculogenesis by controlling the intraovarian activin:inhibin ratio.

PMID- 14585819
TI  - Expression and localization of cathepsin k in adult rat sertoli cells.
AB  - The cathepsins are a family of cysteine proteases that have been broadly
      implicated in proteolytic processes during cell growth, cell development, and
      normal adult cellular function. Cathepsin L is a major secretory product of rat
      and mouse Sertoli cells, the absence of which in furless mice is associated with
      atrophy of some seminiferous tubules. However, furless mice produce viable sperm,
      suggesting the possibility that other members of the cathepsin family of
      proteases may complement cathepsin L action in the testis. Our objective herein
      was to begin to test this hypothesis. To this end, we first utilized cDNA
      microarray technology to identify the members of the cathepsin gene family
      expressed by freshly isolated adult rat Sertoli cells. This approach,
      complemented by Northern blot analyses, showed that in addition to cathepsin L,
      cathepsin K is highly and specifically expressed in Sertoli cells. As is also
      true of cathepsin L, cathepsin K mRNA was found to be expressed by Sertoli cells
      at specific stages of the cycle of the seminiferous epithelium, with maximal
      expression at stages VI-VII. The use of immunocytochemical methods revealed that
      cathepsin K protein localizes to the cytoplasm of Sertoli cells at stages VI
      VIII, to small punctuate lysosomes at stages I-VIII and XIII-XIV, and to early
      and late residual bodies at stages IX-XII. This localization was found to be
      similar to that of cathepsin L. The similarity in the expression and localization
      of cathepsin K and cathepsin L suggest that the two proteases may have similar
      functions. If true, this might explain the fertility of furless mice. Further,
      the results suggest that cathepsin K, in both its secreted and lysosomal forms,
      may play a role in the degradation of Sertoli cell residual bodies.

PMID- 14585820
TI  - Characterization of expression, and cloning, of beta-D-xylosidase and alpha-L
      arabinofuranosidase in developing and ripening tomato (Lycopersicon esculentum
      Mill.) fruit.
AB  - Modifications to the cell wall of developing and ripening tomato fruit are
      mediated by cell wall-degrading enzymes, including a beta-d-xylosidase or alpha-l
      arabinofuranosidase, which participate in the breakdown of xylans and/or
      arabinoxylans. The activity of both enzymes was highest during early fruit
      growth, before decreasing during later development and ripening. Two beta-d
      xylosidase cDNAs, designated LeXYL1 and LeXYL2, and an alpha-l
      arabinofuranosidase cDNA, designated LeARF1, were obtained. Accumulation of mRNAs
      for beta-d-xylosidase and alpha-l-arabinofuranosidase was examined during fruit
      development and ripening. LeARF1 and LeXYL2 genes were relatively highly
      expressed during fruit development and decreased after the onset of ripening. By
      contrast, LeXYL1 was not expressed during fruit development, but was expressed
      later, particularly during over-ripening. The expression of all three genes was
      also followed in ripening-impaired mutants, Nr, Nr2, nor, and rin of cv. Ailsa
      Craig fruit. LeXYL2 mRNA was detected in the ripe fruits of all the mutants and
      its abundance was similar to that in mature green wild-type fruit. By contrast,
      LEXYL1 mRNA was expressed only in the ripe fruits of the Nr mutant, suggesting
      that the two beta-d-xylosidase genes are subject to distinct regulatory control
      during fruit development and ripening. LeARF1 mRNA was detected in ripe fruits of
      Nr2, nor and rin, and not in ripe fruit of the Nr mutant. The accumulation of
      LeARF1 in ripe fruit was restored by 1-methylcyclopropene (1-MCP), an inhibitor
      of ethylene action, while 1-MCP had no effect on the expression of LeXYL1 or
      LeXYL2. This suggests that LeARF1 expression is subject to negative regulation by
      ethylene and that the two beta-d-xylosidase genes are independent of ethylene
      action.

PMID- 14585821
TI  - Expression of Chia4-Pa chitinase genes during somatic and zygotic embryo
      development in Norway spruce (Picea abies): similarities and differences between
      gymnosperm and angiosperm class IV chitinases.
AB  - The developmental pathway of somatic embryogenesis in Norway spruce involves
      proliferation of proembryogenic masses (PEMs), PEM-to-somatic embryo transition
      and further development of the somatic embryos. It has previously been shown that
      extracellular signal molecules, including arabinogalactan proteins, lipo
      chitooligosaccharides and chitinases, regulate somatic embryogenesis. The Chia4
      Pa1 gene from Norway spruce is described here. The Chia4-Pa1 encodes a typical
      basic class IV chitinase, although the intron-exon organization of this
      gymnosperm chitinase is different from that in angiosperm class IV chitinases.
      The Chia4-Pa1 belongs to a small gene family with highly similar members, and the
      expression pattern of Chia4-Pa1 cannot be distinguished from that of other Chia4
      Pa members. Upon withdrawal of plant growth regulators, i.e. during a treatment
      that stimulates PEM-to-somatic embryo transition and massive programmed cell
      death, a significant increase in transcription and translation of Chia4-Pa genes
      takes place. The expression pattern analysis revealed that Chia4-Pa genes are
      expressed in a subpopulation of proliferating cells and at the base of the
      somatic embryo. Furthermore, in seeds, Chia4-Pa genes are expressed in the
      megagametophyte in the single cell-layered zone surrounding the corrosion cavity.
      Taken together these results suggest that the Chia4-Pa expressing cells have a
      megagametophyte signalling function and that CHIA4-Pa stimulates programmed cell
      death and promotes PEM-to-somatic embryo transition.

PMID- 14585822
TI  - Limonene production in tobacco with Perilla limonene synthase cDNA.
AB  - Limonene synthase (LS) catalyses the stereo-specific cyclization of geranyl
      diphosphate (GPP) to form a monocyclic monoterpene, limonene. In an attempt to
      engineer monoterpene biosynthesis, three expression constructs of LS cDNA of
      Perilla frutescens, which were designed to be localized in either the plastid,
      the cytosol or the endoplasmic reticulum (ER), were introduced into tobacco in
      order to examine differences in enzyme activity and the productivity of limonene.
      High and moderate enzyme activity, respectively, was observed for plastid- and
      cytosol-localized LS, whereas no enzyme activity was seen for ER-localized LS,
      suggesting that the plastid is the preferred compartment for LS, while LS may
      also have an active form in the cytosol. The formation of limonene in vivo was
      confirmed by gas chromatography-mass spectrometry (GC-MS) in leaf extracts of
      both plastid- and cytosol-localized LS transgenic plants. The amount of limonene
      in plastid-localized LS transgenic plants was 143 ng g-1 fresh wt, whereas that
      in the cytosol-type was 40 ng g-1 fresh wt, and these limonene contents increased
      by 2.7-fold and 3.0-fold, respectively, with the addition of methyl jasmonate.
      The headspace analyses showed that the plastid- and the cytosol-localized LS
      transgenic plants (12 cm high) emitted 390 ng and 515 ng limonene per month,
      respectively. The possibility of genetically engineering monoterpene production
      is discussed.

PMID- 14585823
TI  - The soybean sucrose binding protein gene family: genomic organization, gene copy
      number and tissue-specific expression of the SBP2 promoter.
AB  - The sucrose binding protein (SBP) from soybean has been implicated as an
      important component of the sucrose uptake system. Two SBP genomic clones,
      gsS641.1 and gsS641.2, which correspond to allelic forms of the GmSBP2/S64 gene,
      have been isolated and characterized. As a member of the seed storage protein
      superfamily, it has been shown that the SBP gene structure is similar to vicilin
      genes with intron/exon boundaries at conserved positions. Fluores cence in situ
      hybridization (FISH) suggested that the soybean SBP gene family is represented by
      at least two non-allelic genes corresponding to the previously isolated GmSBP1
      and GmSBP2/S64 cDNAs. These two cDNAs share extensive sequence similarity but are
      located at different loci in the soybean genome. To investigate transcriptional
      activation of the GmSBP2 gene, 2 kb 5'-flanking sequences of gsS641.1 and
      gsS641.2 were fused to the beta-glucuronidase (GUS) reporter gene and to the
      green fluorescent protein (GFP) reporter gene and inde pendently introduced into
      Nicotiana tabacum by Agrobacterium tumefaciens-mediated transformation. The SBP2
      promoter directed expression of both GUS and GFP reporter genes with high
      specificity to the phloem of leaves, stems and roots. Thus, the overall pattern
      of SBP-GUS or SBP-GFP expression is consistent with the involvement of SBP in
      sucrose translocation-dependent physiological processes.

PMID- 14585824
TI  - Transition metal transporters in plants.
AB  - Transition metals such as Fe, Cu, Mn, and Zn are essential minerals for normal
      plant growth and development, although they can be toxic when present in excess.
      Thus, for healthy plant growth, a range of transition metals must be acquired
      from the soil, distributed around the plant, and their concentrations carefully
      regulated within different cells and organelles. Membrane transport systems are
      likely to play a central role in these processes. The application of powerful
      genetic and molecular techniques has now identified a range of gene families that
      are likely to be involved in transition metal transport. These include the heavy
      metal ATPases (HMAs), the Nramps, the cation diffusion facilitator (CDF) family,
      the ZIP family, and the cation antiporters. This review provides a broad overview
      of the range of potential transport systems now thought to be involved in the
      uptake, distribution and homeostasis of transition metals in plants.

PMID- 14585825
TI  - Transcriptional regulation of secondary growth in Arabidopsis thaliana.
AB  - Despite its economic and environmental significance, understanding the molecular
      biology of secondary growth (i.e. wood formation) in tree species has been
      lagging behind that of primary growth, primarily due to the inherent difficulties
      of tree biology. In recent years, Arabidopsis has been shown to express all of
      the major components of secondary growth. Arabidopsis was induced to undergo
      secondary growth and the transcriptome profile changes were surveyed during
      secondary growth using 8.3 K Arabidopsis Genome Arrays. Twenty per cent of the
      approximately 8300 genes surveyed in this study were differentially regulated in
      the stems treated for wood formation. Genes of unknown function made up the
      largest category of the differentially expressed genes, followed by transcription
      regulation-related genes. Examination of the expression patterns of the genes
      involved in the sequential events of secondary growth (i.e. cell division, cell
      expansion, cell wall biosynthesis, lignification, and programmed cell death)
      identified several key candidate genes for the genetic regulation of secondary
      growth. In order to gain further insight into the transcriptional regulation of
      secondary growth, the expression patterns of the genes encoding transcription
      factors were documented in relation to secondary growth. A computational biology
      approach was used to identify regulatory cis-elements from the promoter regions
      of the genes that were up-regulated in wood-forming stems. The expression
      patterns of many previously unknown genes were established and various existing
      insights confirmed. The findings described in this report should add new
      information that can lead to a greater understanding of the secondary xylem
      formation process.

PMID- 14585826
TI  - Marked modulation by phosphate of phosphoenolpyruvate carboxylase in leaves of
      Amaranthus hypochondriacus, a NAD-ME type C4 plant: decrease in malate
      sensitivity but no change in the phosphorylation status.
AB  - The effect of Pi on the properties of phosphoenolpyruvate carboxylase (PEPC) from
      Amaranthus hypochondriacus, a NAD-ME type C4 plant, was studied in leaf extracts
      as well as with purified protein. Efforts were also made to modulate the Pi
      status of the leaf by feeding leaves with either Pi or mannose. Inclusion of 30
      mM Pi during the assay enhanced the enzyme activity in leaf extracts or of
      purified protein by >2-fold. The effect of Pi on the enzyme purified from dark
      adapted leaves was more pronounced than that from light-adapted ones. The Ki for
      malate increased >2.3-fold and >1.9-fold by Pi in the enzyme purified from dark
      adapted leaves and light-adapted leaves, respectively. Pi also induced an almost
      50-60% increase in Km for PEP or Ka for glucose-6-phosphate. Feeding the leaves
      with Pi also increased the activity of PEPC in leaf extracts, while decreasing
      the malate sensitivity of the enzyme. On the other hand, Pi sequestering by
      mannose marginally decreased the activity, while markedly suppressing the light
      activation, of PEPC. There was no change in phosphorylation of PEPC in leaves of
      A. hypochondriacus due to the feeding of 30 mM Pi. However, feeding with mannose
      decreased the light-enhanced phosphorylation of PEPC. The marked decrease in
      malate sensitivity of PEPC with no change in phosphorylation state indicates that
      the changes induced by Pi are independent of the phosphorylation of PEPC. It is
      suggested here that Pi is an important factor in regulating PEPC in vivo and
      could also be used as a tool to analyse the properties of PEPC.

PMID- 14585827
TI  - Differential distribution of the cognate and heat-stress-induced isoforms of high
      Mr cis-trans prolyl peptidyl isomerase (FKBP) in the cytoplasm and nucleoplasm.
AB  - Wheat root tips express a 73 kDa cognate isoform and a 77 kDa heat-shock-induced
      isoform of peptidyl prolyl cis-trans isomerase (FK506 binding protein; FKBP) that
      is part of a chaperone complex with hsp90. The 73 kDa and 77 kDa FKBPs have very
      similar sequences, differing primarily in the N- and C-terminal 20 amino acids.
      In order to define the potential functional roles of these proteins, the 73 kDa
      and 77 kDa FKBPs were localized in root tips using antigen-affinity purified
      antibodies as a probe. The cognate 73 kDa FKBP is localized in the cytoplasm and
      appears enriched around the periphery of the early vacuole and vesicles exiting
      the trans-Golgi. Parallel assays with antibodies directed against tonoplast
      aquaporin and pyrophosphatase confirmed the association of FKBP with an early
      vacuole compartment. Sucrose gradient centrifugation analysis of root tip lysates
      also showed that 73 kDa FKBP is co-fractionated with tonoplast aquaporin and V
      ATPase in a light compartment near the top of the gradient. Heat-shock treatment
      of root tips induces the accumulation of 77 kDa FKBP while the abundance of 73
      kDa FKBP remains constant. Quantitative EM immunogold assays of the intracellular
      distribution of FKBP over an 8 h heat-shock time-course showed that FKBP is
      initially present in the cytoplasm, but is transported into the nucleus where it
      accumulates in the nucleoplasm and into specific subnuclear domains. The results
      of this study show that the intracellular distribution of the high Mr FKBPs in
      wheat root tips differs at normal and elevated temperatures, indicating different
      functional roles for the FKBP isoforms.

PMID- 14585828
TI  - Variation in acclimation of photosynthesis in Trifolium repens after eight years
      of exposure to Free Air CO2 Enrichment (FACE).
AB  - The initial stimulation of photosynthesis observed on elevation of [CO2] in
      grasslands has been predicted to be a transient phenomenon constrained by the
      loss of photosynthetic capacity due to other limitations, notably nutrients and
      sinks for carbohydrates. Legumes might be expected partially to escape these
      feedbacks through symbiotic N2 fixation. The Free-Air Carbon dioxide Enrichment
      (FACE) experiment at Eschikon, Switzerland, has been the longest running
      investigation of the effects of open-air elevation of [CO2] on vegetation. The
      prediction of a long-term loss of photosynthetic capacity was tested by analysing
      photosynthesis in Trifolium repens L. (cv. Milkanova) in the spring and autumn of
      the eighth, ninth and tenth years of treatment. A high and low N treatment also
      allowed a test of the significance of exogenous N-supply in maintaining a
      stimulation of photosynthetic capacity in the long-term. Prior work in this Free
      Air CO2 Enrichment (FACE) experiment has revealed that elevated [CO2] increased
      both vegetative and reproductive growth of T. repens independent of N treatment.
      It is shown here that the photosynthetic response of T. repens was also
      independent of N fertilization under both current ambient and elevated (600 micro
      mol mol-1) [CO2]. There was a strong effect of season on photosynthesis, with
      light-saturated rates (Asat) 37% higher in spring than in autumn. Higher Asat in
      the spring was supported by higher maximum Rubisco carboxylation rates (Vc,max)
      and maximum rates of electron transport (Jmax) contributing to RuBP regeneration.
      Elevated [CO2] increased Asat by 37% when averaged across all measurement periods
      and both N fertilization levels, and decreased stomatal conductance by 25%. In
      spring, there was no effect of elevated [CO2] on photosynthetic capacity of
      leaves, but in autumn both Vc,max and Jmax were reduced by approximately 20% in
      elevated [CO2]. The results show that acclimation of photosynthetic capacity can
      occur in a nitrogen-fixing species, in the field where there are no artificial
      restrictions on sink capacity. However, even with acclimation there was a highly
      significant increase in photosynthesis at elevated [CO2].

PMID- 14585829
TI  - Local and systemic effects of phosphorus and nitrogen on nodulation and nodule
      function in Alnus incana.
AB  - Phosphorus (P) and nitrogen (N) effects on nodulation, nitrogenase activity and
      plant growth were studied in the root-hair-infected actinorhizal plant Alnus
      incana (L.) Moench. A split-root experiment, as well as a short-term experiment
      with entire root systems and a broader range of P concentrations, showed that P
      effects were specific on nodulation and not a general stimulation via a plant
      growth effect. These results indicate that nodule initiation and nodule growth
      have a high P demand. The split-root assay, comprising seven combinations of two
      N and two P levels, showed that P could counteract systemic N inhibition of
      nodulation, but did not counteract N inhibition of nitrogenase activity.

PMID- 14585832
TI  - Three-dimensional structure of YaaE from Bacillus subtilis, a glutaminase
      implicated in pyridoxal-5'-phosphate biosynthesis.
AB  - The structure of YaaE from Bacillus subtilis was determined at 2.5-A resolution.
      YaaE is a member of the triad glutamine aminotransferase family and functions in
      a recently identified alternate pathway for the biosynthesis of vitamin B(6).
      Proposed active residues include conserved Cys-79, His-170, and Glu-172. YaaE
      shows similarity to HisH, a glutaminase involved in histidine biosynthesis. YaaD
      associates with YaaE. A homology model of this protein was constructed. YaaD is
      predicted to be a (beta/alpha)(8) barrel on the basis of sequence comparisons.
      The predicted active site includes highly conserved residues 211-216 and 233-235.
      Finally, a homology model of a putative YaaD-YaaE complex was prepared using the
      structure of HisH-F as a model. This model predicts that the ammonia molecule
      generated by YaaE is channeled through the center of the YaaD barrel to the
      putative YaaD active site.

PMID- 14585831
TI  - Stress induces mitochondria-mediated apoptosis independent of SAPK/JNK activation
      in embryonic stem cells.
AB  - SAPK/JNK, which belongs to the family of mitogen-activated protein kinase (MAPK),
      is activated by many types of cellular stresses or extracellular signals and is
      involved in embryonic development, immune responses, and cell survival or
      apoptosis. However, the physiological roles of SAPK/JNK in the signaling of
      stress-induced apoptosis are still controversial. To evaluate the precise
      function, SAPK/JNK-inactivated mouse embryonic stem (ES) cells were generated by
      disrupting genes of the MAPK activators, SEK1 and MKK7. Although SAPK/JNK
      activation by various stresses was completely abolished in sek1(-/-) mkk7(-/-) ES
      cells, apoptotic responses including DNA fragmentation and caspase 3 activation
      still occurred normally, which displays a sharp contrast to apaf1(-/-) ES cells
      exhibiting profound defects in the mitochondria-dependent apoptosis. These normal
      apoptotic responses without SAPK/JNK activation were also observed in fibroblasts
      derived from sek1(-/-) mkk7(-/-) ES cells. Instead, interleukin-1 beta (IL-1
      beta)-induced IL-6 gene expression was greatly suppressed in sek1(-/-) mkk7(-/-)
      fibroblasts. These results clearly show that SAPK/JNK activation is responsible
      for the inflammatory cytokine-induced gene expression but not essentially
      required for the mitochondria-dependent apoptosis at least in ES or fibroblast
      like cells, which are prototypes of all cell lineages.

PMID- 14585830
TI  - The nonstructural protein 3 protease/helicase requires an intact protease domain
      to unwind duplex RNA efficiently.
AB  - The nonstructural 3 (NS3) protein encoded by the hepatitis C virus possesses both
      an N-terminal serine protease activity and a C-terminal 3'-5' helicase activity.
      This study examines the effects of the protease on the helicase by comparing the
      enzymatic properties of the full-length NS3 protein with truncated versions in
      which the protease is either deleted or replaced by a polyhistidine (His tag) or
      a glutathione S-transferase fusion protein (GST tag). When the NS3 protein lacks
      the protease domain it unwinds RNA more slowly and does not unwind RNA in the
      presence of excess nucleic acid that acts as an enzyme trap. Some but not all of
      the RNA helicase activity can be restored by adding a His tag or GST tag to the N
      terminus of the truncated helicase, suggesting that the effects of the protease
      are both specific and nonspecific. Similar but smaller effects are also seen in
      DNA helicase and translocation assays. While translocating on RNA (or DNA) the
      full-length protein hydrolyzes ATP more slowly than the truncated protein,
      suggesting that the protease allows for more efficient ATP usage. Binding assays
      reveal that the full-length protein assembles on single-stranded DNA as a higher
      order oligomer than the truncated fragment, and the binding appears to be more
      cooperative. The data suggest that hepatitis C virus RNA helicase, and therefore
      viral replication, could be influenced by the rotations of the protease domain
      which likely occur during polyprotein processing.

PMID- 14585833
TI  - Affinity maturation of leukemia inhibitory factor and conversion to potent
      antagonists of signaling.
AB  - Leukemia inhibitory factor (LIF)-induced cell signaling occurs following
      sequential binding to the LIF receptor alpha-chain (LIFR), then to the gp130 co
      receptor used by all members of the interleukin-6 family of cytokines. By
      monovalently displaying human LIF on the surface of M13 phage and randomizing
      clusters of residues in regions predicted to be important for human LIFR binding,
      we have identified mutations, which lead to significant increases in affinity for
      binding to LIFR. Six libraries were constructed in which regions of 4-6 amino
      acids were randomized then panned against LIFR. Mutations identified in three
      distinct clusters, residues 53-57, 102-103, and 150-155, gave rise to proteins
      with significantly increased affinity for binding to both human and mouse LIFR.
      Combining the mutations for each of these regions further increased the affinity,
      such that the best mutants bound to human LIFR with >1000-fold higher affinity
      than wild-type human LIF. NMR analysis indicated that the mutations did not alter
      the overall structure of the molecule relative to the native protein, although
      some local changes occurred in the vicinity of the substituted residues. Despite
      increases in LIFR binding affinity, these mutants did not show any increase in
      activity as agonists of LIF-induced proliferation of Ba/F3 cells expressing human
      LIFR and gp130 compared with wild-type LIF. Incorporation of two additional
      mutations (Q29A and G124R), which were found to abrogate cell signaling, led to
      the generation of highly potent antagonists of both human and murine LIF-induced
      bioactivity.

PMID- 14585834
TI  - Cathepsin B Is Inhibited in Mutant Cells Selected during Persistent Reovirus
      Infection.
AB  - Persistent reovirus infections of murine L929 (L) fibroblast cells select mutant
      (LX) cells that do not support proteolytic disassembly of reovirus virions within
      the endocytic pathway. To better understand the function and regulation of
      endocytic proteases, we conducted experiments to define the block to reovirus
      disassembly displayed by LX cells. In contrast to parental L cells, mutant LX
      cells harbor defects that interfere with the maturation and activity of cathepsin
      B and cathepsin L but not cathepsin H. The cDNAs encoding cathepsin B and
      cathepsin L in L cells are identical to those in LX cells, indicating that LX
      cells manifest an extrinsic block to the function of these enzymes. Mixed lysates
      of L cells and LX cells lack activity of both cathepsin B and cathepsin L,
      suggesting the presence of an inhibitor of cathepsin function in LX cells. A
      cathepsin B-green fluorescent protein (GFP) fusion protein expressed in L cells
      and purified by immunoprecipitation retains cathepsin B activity, whereas
      cathepsin B-GFP expressed in LX cells does not. However, activity of cathepsin B
      GFP expressed in LX cells can be recovered by incubating the immunoprecipitate
      with L cell lysate followed by immunoprecipitation, providing further evidence
      that LX cells express a cathepsin inhibitor. Native-gel electrophoresis and gel
      filtration chromatography demonstrate that, in both cell lines, the double-chain
      form of cathepsin B is sequestered in a large molecular weight complex that
      renders this form of the enzyme inactive. Alteration of this sequestration
      complex appears to be responsible for inhibition of cathepsin B in LX cells.
      These findings suggest that cathepsins can be regulated within the endocytic
      pathway. Moreover, this regulation influences host cell susceptibility to
      intracellular pathogens.

PMID- 14585835
TI  - Characterization of endostatin binding to heparin and heparan sulfate by surface
      plasmon resonance and molecular modeling: role of divalent cations.
AB  - Endostatin (20 kDa) is a C-terminal proteolytic fragment of collagen XVIII that
      is localized in vascular basement membrane zones in various organs. It binds
      zinc, heparin/heparan sulfate, laminin, and sulfatides and inhibits angiogenesis
      and tumor growth. Here we determined the kinetics and affinity of the interaction
      of endostatin with heparin/heparan sulfate and investigated the effects of
      divalent cations on these interactions and on the biological activities of
      endostatin. The binding of human recombinant endostatin to heparin and heparan
      sulfate was studied by surface plasmon resonance using BIAcore technology and
      further characterized by docking and molecular dynamics simulations. Kinetic
      data, evaluated using a 1:1 interaction model, showed that heparan sulfate bound
      to and dissociated from endostatin faster than heparin and that endostatin bound
      to heparin and heparan sulfate with a moderate affinity (K(D) approximately 2
      microm). Molecular modeling of the complex between endostatin and heparin
      oligosaccharides predicted that, compared with mutagenesis studies, two further
      arginine residues, Arg(47) and Arg(66), participated in the binding. The binding
      of endostatin to heparin and heparan sulfate required the presence of divalent
      cations. The addition of ZnCl(2) to endostatin enhanced its binding to heparan
      sulfate by approximately 40% as well as its antiproliferative effect on
      endothelial cells stimulated by fibroblast growth factor-2, suggesting that this
      activity is mediated by the binding of endostatin to heparan sulfate. In
      contrast, no increase in the antiangiogenic and anti-proliferative activities of
      endostatin promoted by vascular endothelial growth factor was observed upon the
      addition of zinc.

PMID- 14585836
TI  - Studies on substrate recognition by the budding yeast separase.
AB  - Sister chromatid cohesion is resolved at anaphase onset when separase, a site
      specific protease, cleaves the Scc1 subunit of the chromosomal cohesin complex
      that is responsible for holding sister chromatids together. This mechanism to
      initiate anaphase is conserved in eukaryotes from budding yeast to man. Budding
      yeast separase recognizes and cleaves two conserved peptide motifs within Scc1.
      In addition, separase cleaves a similar motif in the kinetochore and spindle
      protein Slk19. Separase may cleave further substrate proteins to orchestrate
      multiple cellular events that take place during anaphase. To investigate
      substrate recognition by budding yeast separase we analyzed the sequence
      requirements at one of the Scc1 cleavage site motifs by systematic mutagenesis.
      We derived a cleavage site consensus motif
      (not(FKRWY))(ACFHILMPVWY)(DE)X(AGSV)R/X. This motif is found in 1,139 of 5,889
      predicted yeast proteins. We analyzed 28 candidate proteins containing this motif
      as well as 35 proteins that contain a core (DE)XXR motif. We could so far not
      confirm new separase substrates, but we have uncovered other forms of mitotic
      regulation of some of the proteins. We studied whether determinants other than
      the cleavage site motif mediate separase-substrate interaction. When the separase
      active site was occupied with a peptide inhibitor covering the cleavage site
      motif, separase still efficiently interacted with its substrate Scc1. This
      suggests that separase recognizes both a cleavage site consensus sequence as well
      as features outside the cleavage site.

PMID- 14585837
TI  - Molecular mechanism of AMD3100 antagonism in the CXCR4 receptor: transfer of
      binding site to the CXCR3 receptor.
AB  - AMD3100 is a symmetric bicyclam, prototype non-peptide antagonist of the CXCR4
      chemokine receptor. Mutational substitutions at 16 positions located in TM-III, 
      IV, -V, -VI, and -VII lining the main ligand-binding pocket of the CXCR4 receptor
      identified three acid residues: Asp(171) (AspIV:20), Asp(262) (AspVI:23), and
      Glu(288) (GluVII:06) as the main interaction points for AMD3100. Molecular
      modeling suggests that one cyclam ring of AMD3100 interacts with Asp(171) in TM
      IV, whereas the other ring is sandwiched between the carboxylic acid groups of
      Asp(262) and Glu(288) from TM-VI and -VII, respectively. Metal ion binding in the
      cyclam rings of AMD3100 increased its dependence on Asp(262) and provided a
      tighter molecular map of the binding site, where borderline mutational hits
      became clear hits for the Zn(II)-loaded analog. The proposed binding site for
      AMD3100 was confirmed by a gradual build-up in the rather distinct CXCR3
      receptor, for which the compound normally had no effect. Introduction of only a
      Glu at position VII:06 and the removal of a neutralizing Lys residue at position
      VII:02 resulted in a 1000-fold increase in affinity of AMD3100 to within 10-fold
      of its affinity in CXCR4. We conclude that AMD3100 binds through interactions
      with essentially only three acidic anchor-point residues, two of which are
      located at one end and the third at the opposite end of the main ligand-binding
      pocket of the CXCR4 receptor. We suggest that non-peptide antagonists with, for
      example, improved oral bioavailability can be designed to mimic this interaction
      and thereby efficiently and selectively block the CXCR4 receptor.

PMID- 14585838
TI  - Astroglial regulation of apolipoprotein E expression in neuronal cells.
      Implications for Alzheimer's disease.
AB  - Although apolipoprotein (apo) E is synthesized in the brain primarily by
      astrocytes, neurons in the central nervous system express apoE, albeit at lower
      levels than astrocytes, in response to various physiological and pathological
      conditions, including excitotoxic stress. To investigate how apoE expression is
      regulated in neurons, we transfected Neuro-2a cells with a 17-kilobase human apoE
      genomic DNA construct encoding apoE3 or apoE4 along with upstream and downstream
      regulatory elements. The baseline expression of apoE was low. However,
      conditioned medium from an astrocytic cell line (C6) or from apoE-null mouse
      primary astrocytes increased the expression of both isoforms by 3-4-fold at the
      mRNA level and by 4-10-fold at the protein level. These findings suggest that
      astrocytes secrete a factor or factors that regulate apoE expression in neuronal
      cells. The increased expression of apoE was almost completely abolished by
      incubating neurons with U0126, an inhibitor of extracellular signal-regulated
      kinase (Erk), suggesting that the Erk pathway controls astroglial regulation of
      apoE expression in neuronal cells. Human neuronal precursor NT2/D1 cells
      expressed apoE constitutively; however, after treatment of these cells with
      retinoic acid to induce differentiation, apoE expression diminished. Cultured
      mouse primary cortical and hippocampal neurons also expressed low levels of apoE.
      Astrocyte-conditioned medium rapidly up-regulated apoE expression in fully
      differentiated NT2 neurons and in cultured mouse primary cortical and hippocampal
      neurons. Thus, neuronal expression of apoE is regulated by a diffusible factor or
      factors released from astrocytes, and this regulation depends on the activity of
      the Erk kinase pathway in neurons.

PMID- 14585839
TI  - Structure of the ubiquitin-interacting motif of S5a bound to the ubiquitin-like
      domain of HR23B.
AB  - Ubiquitination, a modification in which single or multiple ubiquitin molecules
      are attached to a protein, serves signaling functions that control several
      cellular processes. The ubiquitination signal is recognized by downstream
      effectors, many of which carry a ubiquitin-interacting motif (UIM). Such
      interactions can be modulated by regulators carrying a ubiquitin-like (UbL)
      domain, which binds UIM by mimicking ubiquitination. Of them, HR23B regulates the
      proteasomal targeting of ubiquitinated substrates, DNA repair factors, and other
      proteins. Here we report the structure of the UIM of the proteasome subunit S5a
      bound to the UbL domain of HR23B. The UbL domain presents one hydrophobic and two
      polar contact sites for interaction with UIM. The residues in these contact sites
      are well conserved in ubiquitin, but ubiquitin also presents a histidine at the
      interface. The pH-dependent protonation of this residue interferes with the
      access of ubiquitin to the UIM and the ubiquitin-associated domain (UBA), and its
      mutation to a smaller residue increases the affinity of ubiquitin for UIM.

PMID- 14585840
TI  - Ca2+ signaling in identified T-lymphocytes from human intestinal mucosa. Relation
      to hyporeactivity, proliferation, and inflammatory bowel disease.
AB  - Ca2+ entry across the plasma membrane is necessary for the activation and
      proliferation of T-lymphocytes. Human intestinal lamina propria lymphocytes
      physiologically exhibit minimal proliferation in response to antigen receptor
      stimulation when compared with peripheral blood T-lymphocytes. This
      hyporeactivity is partially abolished in inflammatory bowel disease. We
      hypothesized that differences in Ca2+ signaling could be related to the disease.
      To test this possibility, we measured Ca2+ signals in identified lymphocytes from
      human blood and human intestinal mucosa. Ca2+ signals in lamina propria T
      lymphocytes from non-inflamed tissue were drastically reduced when compared with
      Ca2+ signals of blood T-lymphocytes from the same persons. However, Ca2+ signals
      in T-lymphocytes from inflamed intestinal mucosa were much higher than the ones
      from non-inflamed mucosa and almost reached levels of Ca2+ signals in peripheral
      blood T-cells. Furthermore, Ca2+ influx was closely linked to cell proliferation
      in both peripheral blood T-lymphocytes and lamina propria lymphocytes cells. We
      conclude that differences in Ca2+ signaling can explain the differences of T
      lymphocyte reactivity in blood versus lamina propria and, importantly, also
      between T-lymphocytes from inflamed and non-inflamed intestinal mucosa. Ca2+
      channels in the plasma membrane of T-lymphocytes might thus prove an excellent
      target to screen for immunosuppressiva to potentially treat the symptoms of
      inflammatory bowel disease.

PMID- 14585841
TI  - Alix, a protein regulating endosomal trafficking, is involved in neuronal death.
AB  - Alix/AIP1 is a cytoplasmic protein, which was first characterized as an
      interactor of ALG-2, a calcium-binding protein necessary for cell death. Alix has
      also recently been defined as a regulator of the endo-lysosomal system. Here we
      have used post-mitotic cerebellar neurons to test Alix function in caspase
      dependent and -independent cell death. Indeed, these neurons survived when
      cultured in 25 mm potassium-containing medium but underwent apoptosis soon after
      the extracellular potassium was lowered to 5 mm. In agreement with other studies,
      we show that caspases are activated after K+ deprivation, but that inhibition of
      these proteases, using the pancaspase inhibitor boc-aspartyl(OMe)
      fluoromethylketone, has no effect on cell survival. Transfection experiments
      demonstrated that Alix overexpression is sufficient to induce caspase activation,
      whereas overexpression of its C-terminal half, Alix-CT, blocks caspase activation
      and cell death after K+ deprivation. We also define a 12-amino acid PXY repeat of
      the C-terminal proline-rich domain necessary for binding ALG-2. Deletion of this
      domain in Alix or in Alix-CT abolished the effects of the overexpressed proteins
      on neuronal survival, demonstrating that the ALG-2-binding region is crucial for
      the death-modulating function of Alix. Overall, these findings define the
      Alix/ALG-2 complex as a regulator of cell death controlling both caspase
      dependent and -independent pathways. They also suggest a molecular link between
      the endo-lysosomal system and the effectors of the cell death machinery.

PMID- 14585842
TI  - KvLQT1 modulates the distribution and biophysical properties of HERG. A novel
      alpha-subunit interaction between delayed rectifier currents.
AB  - Cardiac repolarization is under joint control of the slow (IKs) and rapid (IKr)
      delayed rectifier currents. Experimental and clinical evidence indicates
      important functional interactions between these components. We hypothesized that
      there might be more direct interactions between the KvLQT1 and HERG alpha
      subunits of IKs and IKr and tested this notion with a combination of biophysical
      and biochemical techniques. Co-expression of KvLQT1 with HERG in a mammalian
      expression system significantly accelerated HERG current deactivation at
      physiologically relevant potentials by increasing the contribution of the fast
      component (e.g. upon repolarization from +20 mV to -50 mV: from 20 +/- 3 to 32 +/
      5%, p < 0.05), making HERG current more like native IKr. In addition, HERG
      current density was approximately doubled (e.g. tail current after a step to +10
      mV: 18 +/- 3 versus 39 +/- 7 pA/picofarad, p < 0.01) by co-expression with
      KvLQT1. KvLQT1 co-expression also increased the membrane immunolocalization of
      HERG by approximately 2-fold (p < 0.05). HERG and KvLQT1 co-immunolocalized in
      canine ventricular myocytes and co-immunoprecipitated in cultured Chinese hamster
      ovary cells as well as in native cardiac tissue, indicating physical interactions
      between HERG and KvLQT1 proteins in vitro and in vivo. Protein interaction assays
      also demonstrated binding of KvLQT1 (but not another K+ channel alpha-subunit,
      Kv3.4) to a C-terminal HERG glutathione S-transferase fusion protein. Co
      expression with HERG did not affect the membrane localization or ionic current
      properties of KvLQT1. This study shows that the alpha-subunit of IKs can interact
      with and modify the localization and current-carrying properties of the alpha
      subunit of IKr, providing potentially novel insights into the molecular function
      of the delayed rectifier current system.

PMID- 14585843
TI  - Reorganization of the Mu transpososome active sites during a cooperative
      transition between DNA cleavage and joining.
AB  - Transposition of mobile genetic elements proceeds through a series of DNA
      phosphoryl transfer reactions, with multiple reaction steps catalyzed by the same
      set of active site residues. Mu transposase repeatedly utilizes the same active
      site DDE residues to cleave and join a single DNA strand at each transposon end
      to a new, distant DNA location (the target DNA). To better understand how DNA is
      manipulated within the Mu transposase-DNA complex during recombination, the
      impact of the DNA immediately adjacent to the Mu DNA ends (the flanking DNA) on
      the progress of transposition was investigated. We show that, in the absence of
      the MuB activator, the 3 '-flanking strand can slow one or more steps between DNA
      cleavage and joining. The presence of this flanking DNA strand in just one active
      site slows the joining step in both active sites. Further evidence suggests that
      this slow step is not due to a change in the affinity of the transpososome for
      the target DNA. Finally, we demonstrate that MuB activates transposition by
      stimulating the reaction step between cleavage and joining that is otherwise
      slowed by this flanking DNA strand. Based on these results, we propose that the 3
      '-flanking DNA strand must be removed from, or shifted within, both active sites
      after the cleavage step; this movement is coupled to a conformational change
      within the transpososome that properly positions the target DNA simultaneously
      within both active sites and thereby permits joining.

PMID- 14585844
TI  - Regulation of beta1C and beta1A integrin expression in prostate carcinoma cells.
AB  - beta(1C) and beta(1A) integrins are two splice variants of the human beta(1)
      integrin subfamily that act as an inhibitor and a stimulator of cell
      proliferation, respectively. In neoplastic prostate epithelium, both these
      variants are down-regulated at the mRNA level, but only beta(1C) protein levels
      are reduced. We used an experimental model consisting of PNT1A, a normal
      immortalized prostate cell line, and LNCaP and PC-3, two prostate carcinoma cell
      lines, to investigate both the transcription/post-transcription and
      translation/post-translation processes of beta(1C) and beta(1A). Transcriptional
      regulation played the key role for the reduction in beta(1C) and beta(1A) mRNA
      expression in cancer cells, as beta(1C) and beta(1A) mRNA half-lives were
      comparable in normal and cancer cells. beta(1C) translation rate decreased in
      cancer cells in agreement with the decrease in mRNA levels, whereas beta(1A)
      translation rate increased more than 2-fold, despite the reduction in mRNA
      levels. Both beta(1C) and beta(1A) proteins were degraded more rapidly in cancer
      than in normal cells, and pulse-chase experiments showed that intermediates
      and/or rates of beta(1C) and beta(1A) protein maturation differ in cancer versus
      normal cells. Inhibition of either calpain- or lysosomal-mediated proteolysis
      increased both beta(1C) and beta(1A) protein levels, the former in normal but not
      in cancer cells and the latter in both cell types, albeit at a higher extent in
      cancer than in normal cells. Interestingly, inhibition of the ubiquitin
      proteolytic pathway increased expression of ubiquitinated beta(1C) protein
      without affecting beta(1A) protein levels in cancer cells. These results show
      that transcriptional, translational, and post-translational processes, the last
      involving the ubiquitin proteolytic pathway, contribute to the selective loss of
      beta(1C) integrin, a very efficient inhibitor of cell proliferation, in prostate
      malignant transformation.

PMID- 14585845
TI  - Peptidoglycan recognition protein tag7 forms a cytotoxic complex with heat shock
      protein 70 in solution and in lymphocytes.
AB  - The peptidoglycan recognition protein Tag7 is shown to form a stable 1:1 complex
      with the major stress protein Hsp70. Neither protein is cytotoxic by itself, but
      their complex induces apoptotic death in several tumor-derived cell lines even at
      subnanomolar concentrations. The minimal part of Hsp70 needed to evoke
      cytotoxicity is residues 450-463 of its peptide-binding domain, but full
      cytotoxicity requires its ATPase activity; remarkably, Tag7 liberated from the
      complex at high ATP is not cytotoxic. The Tag7-Hsp70 complex is produced by tag7
      transfected cells and by lymphokine-activated killers, being assembled within the
      cell and released into the medium through the Golgi apparatus by a mechanism
      different from the commonly known granule exocytosis. Thus, we demonstrate how a
      heat shock protein may perform functions clearly distinct from chaperoning or
      cell rescue and how peptidoglycan recognition proteins may be involved in innate
      immunity and anti-cancer defense.

PMID- 14585846
TI  - Cell type-specific expression of the IkappaB kinases determines the significance
      of phosphatidylinositol 3-kinase/Akt signaling to NF-kappa B activation.
AB  - Phosphatidylinositol (PI) 3-kinase/Akt signaling activates NF-kappa B through
      pleiotropic, cell type-specific mechanisms. This study investigated the
      significance of PI 3-kinase/Akt signaling to tumor necrosis factor (TNF)-induced
      NF-kappa B activation in transformed, immortalized, and primary cells.
      Pharmacological inhibition of PI 3-kinase blocked TNF-induced NF-kappa B DNA
      binding in the 293 line of embryonic kidney cells, partially affected binding in
      MCF-7 breast cancer cells, HeLa and ME-180 cervical carcinoma cells, and NIH 3T3
      cells but was without significant effect in H1299 and human umbilical vein
      endothelial cells, cell types in which TNF activated Akt. NF-kappa B is retained
      in the cytoplasm by inhibitory proteins, I kappa Bs, which are phosphorylated and
      targeted for degradation by I kappa B kinases (IKK alpha and IKK beta).
      Expression and the ratios of IKK alpha and IKK beta, which homo- and
      heterodimerize, varied among cell types. Cells with a high proportion of IKK
      alpha (the IKK kinase activated by Akt) to IKK beta were most sensitive to PI 3
      kinase inhibitors. Consequently, transient expression of IKK beta diminished the
      capacity of the inhibitors to block NF-kappa B DNA binding in 293 cells. Also,
      inhibitors of PI 3-kinase blocked NF-kappa B DNA binding in Ikk beta-/- but not
      Ikk alpha-/- or wild-type cells in which the ratio of IKK alpha to IKK beta is
      low. Thus, noncoordinate expression of I kappa B kinases plays a role in
      determining the cell type-specific role of Akt in NF-kappa B activation.

PMID- 14585847
TI  - Protein phosphatase 2Cbeta association with the IkappaB kinase complex is
      involved in regulating NF-kappaB activity.
AB  - The NF-kappaB pathway is important in the control of the immune and inflammatory
      response. One of the critical events in the activation of this pathway is the
      stimulation of the IkappaB kinases (IKKs) by cytokines such as tumor necrosis
      factor-alpha and interleukin-1. Although the mechanisms that modulate IKK
      activation have been studied in detail, much less is known about the processes
      that down-regulate its activity following cytokine treatment. In this study, we
      utilized biochemical fractionation and mass spectrometry to demonstrate that
      protein phosphatase 2Cbeta (PP2Cbeta) can associate with the IKK complex.
      PP2Cbeta association with the IKK complex led to the dephosphorylation of IKKbeta
      and decreased its kinase activity. The binding of PP2Cbeta to IKKbeta was
      decreased at early times post-tumor necrosis factor-alpha treatment and was
      restored at later times following treatment with this cytokine. Experiments
      utilizing siRNA directed against PP2Cbeta demonstrated an in vivo role for this
      phosphatase in decreasing IKK activity at late times following cytokine
      treatment. These studies are consistent with the ability of PP2Cbeta to down
      regulate cytokine-induced NF-kappaB activation by altering IKK activity.

PMID- 14585848
TI  - The parathyroid hormone mRNA 3'-untranslated region AU-rich element is an
      unstructured functional element.
AB  - Parathyroid hormone (PTH) gene expression is regulated post-transcriptionally by
      hypocalcemia and hypophosphatemia. This regulation is dependent upon binding of
      protective trans-acting factors to a specific element in the PTH mRNA 3'
      untranslated region (UTR). We have previously demonstrated that a 63-nucleotide
      (nt) AU-rich PTH mRNA element is sufficient to confer regulation of RNA stability
      by calcium and phosphate in an in vitro degradation assay (IVDA). The 63-nt
      element consists of a core 26-nt minimal binding sequence and flanking regions.
      We have now studied the functionality of this element in HEK293 cells using
      reporter genes and showed that it destabilizes mRNAs for green fluorescent
      protein (GFP) and growth hormone, similar to its effect in the IVDA. To
      understand how the cis-element functions as an instability element, we have
      analyzed its structure by RNase H, primer extension, and computer modeling. The
      results indicate that the PTH mRNA 3'-UTR and in particular the region of the cis
      element are dominated by significant open regions with little folded base
      pairing. Mutation analysis of the 26-nt core element demonstrated the importance
      of defined nucleotides for protein-RNA binding. In the GFP reporter system, the
      same mutations that prevented binding were also ineffective in destabilizing GFP
      mRNA in HEK293 cells. This is the first study of an AU-rich element that relates
      function to structure. The PTH mRNA 3'-UTR cis-acting element is an open region
      that utilizes the distinct sequence pattern to determine mRNA stability by its
      interaction with trans-acting factors.

PMID- 14585849
TI  - Immunostimulatory CpG treatment for genital HSV-2 infections.

PMID- 14585850
TI  - Ciprofloxacin-resistant Escherichia coli from bacteraemias in England;
      increasingly prevalent and mostly from men.
AB  - OBJECTIVES: To assess ciprofloxacin resistance among Escherichia coli isolates
      from bacteraemia patients in England in relation to age, sex and Region. METHODS:
      Routine susceptibility data for bacteraemia isolates were collected from over 90%
      of hospitals in England. RESULTS: During 1995-2001, the prevalence of
      ciprofloxacin resistance trebled, from 2.1% to 6.5%. Isolates from men were more
      frequently resistant than those from women, possibly because infections in men
      more often involve nosocomial strains. Resistance was rare (<1.5%) in isolates
      from patients aged <1 year; among older patients, resistance was unrelated to age
      in isolates from women, but peaked in the 15-44 age group for men. CONCLUSIONS:
      The prevalence of ciprofloxacin resistance in E. coli from bacteraemia is
      strongly associated with sex and, to a lesser extent, age.

PMID- 14585851
TI  - In vitro effects of combinations of antipseudomonal agents against seven strains
      of multidrug-resistant Pseudomonas aeruginosa.
AB  - OBJECTIVES: The aim of this study was to evaluate the combined effects of
      antibiotic combinations by agar incorporation inhibitory tests and by time-kill
      tests on seven geographically and epidemiologically distinct isolates of
      multidrug-resistant Pseudomonas aeruginosa. All seven strains were resistant to
      piperacillin, meropenem, ceftazidime, cefoperazone-sulbactam, aztreonam, amikacin
      and ciprofloxacin. METHODS: Strains were distinguished by pulsed-field gel
      electrophoresis after DNA extraction and restriction with SpeI. MICs of the seven
      antibiotics listed above were determined by agar dilution. The effect of
      combinations of these agents was determined by agar incorporation tests and by
      time-kill studies. RESULTS: Among the two-drug combinations, the combination
      aztreonam and amikacin was the most effective, inhibiting proliferation in five
      of the seven strains. Among the three-drug combinations, the combinations of
      piperacillin, ceftazidime and amikacin, and that of ceftazidime, aztreonam and
      amikacin were the most effective, inhibiting proliferation in all seven strains.
      In the killing tests, the three-drug combination of ceftazidime, aztreonam and
      amikacin was the most effective. This three-drug combination had bacteriostatic
      effects on all seven strains 2, 4, 6 and 24 h after drug addition, synergic
      effects on 2-3 strains and bactericidal effects on 1-2 strains after 4, 6 and 24
      h. CONCLUSIONS: The three-drug combination of ceftazidime, aztreonam and amikacin
      may be effective against P. aeruginosa resistant to all commonly used
      antipseudomonal drugs, and deserves further study.

PMID- 14585852
TI  - Garlic extract and two diallyl sulphides inhibit methicillin-resistant
      Staphylococcus aureus infection in BALB/cA mice.
AB  - OBJECTIVES: The inhibitory effect of garlic extract, diallyl sulphide and diallyl
      disulphide against methicillin-resistant Staphylococcus aureus (MRSA) infection
      in BALB/cA mice was studied. The influence of these agents upon the levels of
      fibronectin, interleukin-6 and lipid oxidation in MRSA-infected mice was
      examined. METHODS: Garlic extract at 100% and 50%; diallyl sulphide (DAS) at 10%
      and 5%; diallyl disulphide (DADS) at 1% and 0.5% were used in this study. Sixteen
      clinical MRSA isolates obtained from infected patients were used in this study
      (n=16). Mice were infected by injecting 200 microL MRSA-PBS solution, which
      contained 10(7) cfu, via the tail vein. At 16 h post-infection (p.i.), garlic
      extract, DAS or DADS at 200 microL was administrated orally. At 24 h p.i., mice
      were killed and blood, liver, kidney and spleen of each mouse were collected.
      Plasma and the filtrate from each organ and serial dilutions were used to
      determine colony count. Plasma fibronectin level was determined by rabbit anti
      rat fibronectin antibody and quantified by ELISA. Interleukin-6 levels were
      determined by commercial kit. Lipid oxidation was determined by measuring
      malondialdehyde levels. RESULTS: The oral administration of these agents
      significantly decreased the viability of MRSA, in plasma, liver, kidney and
      spleen (P<0.05). MRSA infection significantly increased fibronectin and
      interleukin-6 levels in plasma of MRSA-infected mice (P<0.05); however, the oral
      administration of garlic extract and two diallyl sulphides significantly reduced
      both fibronectin and interleukin-6 levels (P<0.05). MRSA infection also
      significantly enhanced lipid oxidation in plasma and three organs (P<0.05). The
      treatments of garlic extract and two diallyl sulphides significantly decreased
      the malondialdehyde level and showed antioxidant protection (P<0.05).
      CONCLUSIONS: These data strongly supported the conclusion that garlic extract,
      diallyl sulphide and diallyl disulphide possessed multiple protective functions
      against MRSA infection, in which diallyl sulphide and diallyl disulphide could be
      considered as novel therapeutic agents for the treatment of MRSA infection.

PMID- 14585853
TI  - AmBisome administration for Candida albicans shunt infections.

PMID- 14585854
TI  - Contribution of beta-lactamase and PBP amino acid substitutions to
      amoxicillin/clavulanate resistance in beta-lactamase-positive,
      amoxicillin/clavulanate-resistant Haemophilus influenzae.
AB  - The roles of beta-lactamase and alterations in penicillin-binding protein in the
      development of amoxicillin and amoxicillin/clavulanate resistance in two beta
      lactamase-positive, amoxicillin/clavulanate-resistant (BLPACR) strains of
      Haemophilus influenzae were investigated. Seven beta-lactamase-negative,
      ampicillin-resistant (BLNAR) strains were also studied for comparison of their
      resistance mechanisms. All strains had been recovered from patients in Japan. The
      TEM type beta-lactamase of the two BLPACR strains had 100% homology with the
      amino acid sequences of published TEM-1 beta-lactamase, showing that
      amoxicillin/clavulanate resistance was not associated with mutations in this beta
      lactamase. However, these strains, as well as the seven BLNAR strains, had
      multiple mutations in ftsI, which encodes penicillin binding protein 3 (PBP3).
      The transformation of H. influenzae Rd strain with amplified ftsI genes from two
      BLPACR and two BLNAR strains enabled the selection of amoxicillin/clavulanate
      resistant transformants with the same mutations as their parent strains. We
      concluded that amoxicillin/clavulanate resistance in the two BLPACR strains was
      due to changes in PBP3. The possibility of the presence of an extended spectrum
      beta-lactamase was excluded in the BLPACR strains studied.

PMID- 14585855
TI  - Sulphonamide resistance gene sul3 found in Escherichia coli isolates from human
      sources.
AB  - OBJECTIVES: The aim of this study was to investigate the molecular basis of an
      observed increasing resistance to trimethoprim and sulphonamides despite a
      simultaneous decline in co-trimoxazole consumption. The distribution of
      sulphonamide resistance genes sul1, sul2 and the recently discovered sul3 was
      studied in a collection of clinical isolates of Enterobacteriaceae. METHODS: PCR
      with primers specific for sul1, sul2 and sul3 was used to detect the three known
      sulphonamide resistance genes in the isolate collection. Sequence analysis was
      used for confirmation of results. Restriction endonuclease digestion and
      conjugational transfer assays were used for plasmid analysis. RESULTS: In 64
      sulphonamide-resistant isolates, 39 sul1 genes and 48 sul2 genes were detected.
      Twenty-five isolates carried both sul1 and sul2 and two were negative for both
      genes. With PCR and sequence analysis these two were shown to harbour the new
      sulphonamide resistance gene sul3, which was carried by different plasmids.
      CONCLUSIONS: Sulphonamide resistance gene sul3, which is widespread among pigs in
      Switzerland, has now also been identified in two different clinical isolates of
      Escherichia coli, located in urinary tract infections in patients in Sweden.

PMID- 14585856
TI  - In vitro activity and synergy of bismuth thiols and tobramycin against
      Burkholderia cepacia complex.
AB  - OBJECTIVES: To determine the susceptibility of Burkholderia multivorans and
      Burkholderia cenocepacia to bismuth-thiols (BTs), and to examine the synergistic
      effects of tobramycin and subinhibitory concentrations of BTs against these
      organisms. METHODS: The susceptibilities of 25 clinical isolates each of B.
      multivorans and B. cenocepacia to six BTs were measured by broth dilution in
      accordance with NCCLS protocols. Ten strains were selected to evaluate the
      antimicrobial interaction between BTs and tobramycin. Fractional inhibitory
      concentration (FIC) and fractional bactericidal concentration (FBC) indices were
      calculated to assess synergy. RESULTS: B. multivorans and B. cenocepacia showed a
      wide range of susceptibilities to BTs. Bismuth ethanedithiol (BisEDT) was one of
      the more potent BTs against these organisms (MIC50 7.8 microM), and was selected
      for synergy studies. Selected strains were highly resistant to tobramycin. The
      addition of subinhibitory concentrations of BisEDT (2 microM) reduced the MIC and
      MBC of tobramycin against all strains, achieving synergy in many instances. The
      FIC index was in the range 0.28-0.66 and the FBC in the range 0.12-0.85. Most
      strains became susceptible to tobramycin at clinically achievable concentrations
      in the presence of non-toxic BisEDT levels. CONCLUSIONS: Treatment with
      subinhibitory BisEDT and tobramycin reduces the MICs and MBCs for B. multivorans
      and B. cenocepacia. BTs may represent an important adjunctive therapy for
      resistant Burkholderia cepacia complex.

PMID- 14585857
TI  - Spread of low-level carbapenem-resistant Acinetobacter baumannii clones in a
      tertiary care Greek hospital.

PMID- 14585858
TI  - Emergence of a fluoroquinolone-resistant strain of Streptococcus pneumoniae in
      England.
AB  - OBJECTIVE: To determine the epidemiological relationship between pneumococci of
      serotype 9V, with reduced susceptibility to ciprofloxacin, penicillin and
      erythromycin, referred to the Reference Laboratory during 1997-2001. METHODS:
      Isolates were characterized by multilocus sequence typing (MLST), PFGE, and
      sequencing of parC and gyrA. Relevant clinical data were sought. RESULTS: Forty
      eight isolates were received from nine laboratories in England, but 35 (73%) were
      from one laboratory in Birmingham, and were mostly from elderly patients
      receiving ofloxacin or ciprofloxacin for respiratory infections. There were two
      quinolone resistance phenotypes, with ciprofloxacin, moxifloxacin and
      gemifloxacin MICs of 8-32, 0.5-1 and 0.125-0.25 mg/L, and 64-256, 4-16 and 1-4
      mg/L, respectively. Each of three isolates from the former group had mutations in
      parC, whereas each of nine isolates from the more resistant group had mutations
      in both parC and gyrA. Several also had increased quinolone efflux. Typing of 27
      quinolone-resistant isolates showed that eight were indistinguishable from the
      epidemic Spain9V-3 (ST156) clone, while the remainder belonged to a novel but
      related type (ST609), that differed from Spain9V-3 at 2/7 alleles (2 bp changes
      in aroE and 1 bp change in gdh). Both MLST types were represented among isolates
      with high- and low-level quinolone resistance. Three of five serotype 9V isolates
      from Birmingham, with reduced susceptibility to penicillin and erythromycin, and
      ciprofloxacin MICs of 1-2 mg/L, belonged to MLST type ST609, while another was
      indistinguishable from the Spain9V-3 clone. Review of records of 32 patients from
      Birmingham indicated that some isolates were nosocomial, whereas others were
      acquired in the community. CONCLUSIONS: In the late 1990s, a quinolone-resistant
      strain, clonally related to Spain9V-3, emerged in England, principally in
      Birmingham.

PMID- 14585859
TI  - Steady-state pharmacokinetics of intravenous colistin methanesulphonate in
      patients with cystic fibrosis.
AB  - OBJECTIVES: To define the steady-state pharmacokinetics of colistin
      methanesulphonate and colistin in patients with cystic fibrosis (CF) following
      intravenous administration of the former. MATERIALS AND METHODS: The study was
      conducted in 12 patients with CF following intravenous administration of colistin
      methanesulphonate (1.63-3.11 mg/kg) every 8 h for at least 2 days. On the day of
      study, four blood samples were collected from each patient at 60, 120, 240 and
      360 min after the end of the infusion. Concentrations of colistin
      methanesulphonate and colistin in plasma were measured separately by HPLC.
      RESULTS: At steady-state, colistin methanesulphonate had a mean (+/- S.D.) total
      body clearance, volume of distribution and half-life of 2.01 +/- 0.46 mL/min per
      kg, 340 +/- 95 mL/kg and 124 +/- 52 min, respectively. Colistin had a
      significantly longer mean half-life of 251 +/- 79 min (P<0.001). With the regimen
      used, colistin methanesulphonate was well tolerated. This is the first report on
      the pharmacokinetics of colistin methanesulphonate in CF patients determined
      using concentrations of colistin methanesulphonate and colistin in plasma.
      CONCLUSIONS: Based on the in vitro pharmacodynamics against Pseudomonas
      aeruginosa previously published by our group and these pharmacokinetic findings,
      dose escalating trials may be warranted to maximize efficacy.

PMID- 14585860
TI  - Time-kill curves as a tool for targeting ceftazidime serum concentration during
      continuous infusion.

PMID- 14585861
TI  - Worldwide incidence, molecular epidemiology and mutations implicated in
      fluoroquinolone-resistant Streptococcus pneumoniae: data from the global PROTEKT
      surveillance programme.
AB  - OBJECTIVES: To analyse the mutations and epidemiology associated with
      fluoroquinolone-resistant pneumococci collected as part of the PROTEKT global
      surveillance programme during 1999-2000. METHODS: Sixty-nine centres in 25
      countries submitted a total of 3362 Streptococcus pneumoniae isolates, for which
      the MICs of antimicrobial agents were determined using NCCLS methodology.
      RESULTS: Levofloxacin resistance was low overall (1% worldwide), with higher
      rates in: Hong Kong (14.3%), South Korea (2.9%), USA (1.8%), Mexico (1.5%),
      Canada (1.4%) and Japan (1.3%). Levofloxacin resistance was very low or absent in
      European countries, and absent in Australia. Worldwide, there was a total of 35
      levofloxacin-resistant isolates, of which 22 (63%) were resistant and 10 (29%)
      were intermediate to moxifloxacin. All levofloxacin-resistant isolates were
      susceptible to telithromycin (< or =0.5 mg/L), linezolid (< or =2 mg/L) and
      quinupristin/dalfopristin (< or =1 mg/L). One or more mutations in the
      topoisomerase genes were identified in all levofloxacin-resistant isolates; most
      of these isolates (33/35) had a mutation in one of the DNA gyrase encoding genes
      (gyrA, gyrB) and one of the topoisomerase IV encoding genes (parC, parE).
      Eighteen (51%) isolates carried the same combination of amino acid substitutions:
      Ser-81-->Phe in GyrA and Ser-79-->Phe in ParC. Isolates displaying a levofloxacin
      MIC of 2-4 mg/L generally had no mutation or one mutation in either a DNA gyrase
      or a topoisomerase IV gene, although most mutations were in parC. CONCLUSIONS:
      Most levofloxacin-resistant isolates possess two mutations (one in DNA gyrase and
      one in topoisomerase IV). Although multilocus sequence typing demonstrated that
      most of these isolates were unrelated, 12 (34%) were the Spain23F-1 clone: 10
      from Hong Kong and one each from Saskatchewan, Canada and Sao Paulo, Brazil.

PMID- 14585862
TI  - Modelling of escalating outpatient antibiotic expenditures.
AB  - OBJECTIVES: To model the relative role of old and newly introduced antibiotics in
      shaping increased antibiotic use. METHODS: Grouped data covering nationwide
      consumption and expenditure for out-of-hospital antibiotics in Greece (1990-1999)
      were used. The antibiotic formulations were categorized into 'common old
      formulations', 'old formulations with intermittent sales', 'recast formulations'
      and 'new substances'. The effect of each category was investigated based on index
      and pricing analyses. RESULTS: We estimated a 143% net increase in out-of
      hospital antibiotic use during 1990-1999. The increase was 59% when all
      formulations of antibiotic substances available by 1990 were considered. A rapid
      turnaround of formulations of old substances was noticed with 669 formulations
      marketed during the decade. Sixteen new antibiotic substances were first
      introduced after 1990 and by 1999 they accounted for 34.9% of total out-of
      hospital antibiotic expenditures. Three new antibiotics (a macrolide and two
      cephalosporins) accounted for over 90% of this amount. For all three, other less
      expensive alternatives were available. CONCLUSIONS: In the studied setting, out
      of-hospital antibiotic use has been expanding in a highly substance-specific and
      non-rational fashion that is accelerated by the introduction of new drugs.

PMID- 14585863
TI  - Piperacillin-tazobactam versus ciprofloxacin plus amoxicillin in the treatment of
      infective episodes after liver transplantation.
AB  - An optimum antimicrobial regimen for bacterial infection after orthotopic liver
      transplantation has not been identified. In this prospective 4 year study of
      patients undergoing liver transplantation, patients were randomized to receive
      either piperacillin-tazobactam (112 patient episodes) or ciprofloxacin plus
      amoxicillin (105 patient episodes) for empirical treatment of infective episodes
      in the first 3 months after transplant. Metronidazole was added to the
      ciprofloxacin-amoxicillin regimen where anaerobic infection was suspected.
      Patient groups were comparable with respect to clinical, biochemical and
      haematological parameters. At the 72 h primary efficacy end-point, the overall
      response rate for the intention-to-treat group was 74/112 (66.1%) for
      piperacillin-tazobactam and 63/105 (60.0%) for ciprofloxacin plus amoxicillin
      (P=0.399); the corresponding figures for the per-protocol (PP) group were 73/82
      (89.0%) (piperacillin-tazobactam) and 61/80 (76.3%) (ciprofloxacin plus
      amoxicillin) (P=0.038). At the end-of-study assessment, 58.9% of episodes in the
      piperacillin-tazobactam group had a successful clinical outcome, compared with
      50.5% in the ciprofloxacin plus amoxicillin group (P=0.222); the corresponding
      figures for the PP group were 83.5% (piperacillin-tazobactam) and 68.8%
      (ciprofloxacin plus amoxicillin) (P=0.038). Staphylococci and aerobic Gram
      negative bacilli were the predominant pathogens in both groups. Bacteria
      resistant to the study drugs were encountered, including methicillin-resistant
      Staphylococcus aureus, vancomycin-resistant Enterococcus faecium and multiply
      resistant Klebsiella spp. Empirical monotherapy with piperacillin-tazobactam is
      an effective treatment for infective episodes in liver transplant patients.

PMID- 14585864
TI  - Comparison of BSAC agar dilution and NCCLS broth microdilution MIC methods for in
      vitro susceptibility testing of Streptococcus pneumoniae, Haemophilus influenzae
      and Moraxella catarrhalis: the BSAC Respiratory Resistance Surveillance
      Programme.
AB  - OBJECTIVE: The aim of this study was to establish the degree of comparability
      between the NCCLS broth microdilution and BSAC agar dilution MIC methods of
      antimicrobial susceptibility testing. METHODS: Six hundred and sixty-one clinical
      isolates of Streptococcus pneumoniae, 936 Haemophilus influenzae and 421
      Moraxella catarrhalis, collected in the winter of 1999-2000 by 20 laboratories in
      the UK and Eire from patients with presumed community-acquired lower respiratory
      infections, were tested by the two methods. MIC agreement was defined as
      excellent (good) if results were within +/- 1 doubling dilution for > or =90% (>
      or =80%) of isolates and within +/- 2 doubling dilutions for > or =95%. Isolates
      were categorized as susceptible, intermediate or resistant using the breakpoints
      appropriate to the testing method. RESULTS: MIC agreement was good or excellent
      in 27 of 36 organism-agent combinations. Agreement was less for M. catarrhalis
      than for other species, and lower in all three species for cefaclor and
      trimethoprim than for other antimicrobials. Discrepancies in categorization
      occurred only occasionally, and were generally explained by differences in
      breakpoints rather than in measured MICs. One exception was S. pneumoniae with
      penicillin. Despite excellent MIC agreement and identical breakpoints, 9% of
      these had minor discrepancies, mainly because 7% of isolates were found
      intermediate by the BSAC method but resistant by the NCCLS method. CONCLUSION:
      There is generally very good agreement between the MICs obtained by the BSAC agar
      dilution and NCCLS broth microdilution methods in this population of isolates,
      comparable to the level of agreement achieved between different laboratories
      using a single method. Breakpoint differences contribute to most of the
      discrepancies in susceptibility categorization.

PMID- 14585865
TI  - Antimicrobial susceptibility of lower respiratory tract pathogens in Great
      Britain and Ireland 1999-2001 related to demographic and geographical factors:
      the BSAC Respiratory Resistance Surveillance Programme.
AB  - OBJECTIVE: The aim of this study was to assess the antimicrobial susceptibility
      of community-acquired lower respiratory pathogens in Great Britain and Ireland,
      and investigate its relationship with demographic and geographical factors using
      multiple logistic regression analysis. METHODS: A total of 1328 isolates of
      Streptococcus pneumoniae, 1894 Haemophilus influenzae and 845 Moraxella
      catarrhalis were collected from lower respiratory clinical specimens (primarily
      sputum) by 20 laboratories in Great Britain (England, Wales and Scotland) and
      Ireland (Northern Ireland and Eire) between 1999 and 2001. RESULTS: Of 1154 S.
      pneumoniae from Great Britain, 92-100% were susceptible to beta-lactams (only
      0.2% having penicillin MICs > or =2 mg/L), 89% were susceptible to erythromycin,
      93% susceptible to tetracycline, and 94-100% intermediate or susceptible to
      fluoroquinolones. Susceptibility to agents other than fluoroquinolones was less
      frequent in the 174 isolates from Ireland: beta-lactam susceptibility was 68-99%
      (3.4% having penicillin MICs > or =2 mg/L), erythromycin susceptibility was 78%
      and tetracycline susceptibility was 82%. In multivariate analysis, susceptibility
      in S. pneumoniae was associated with country and patient age, being most common
      overall in the 20-49 years age group. Of 1894 H. influenzae, 15% produced beta
      lactamase and 79-100% were susceptible to beta-lactams other than cefaclor.
      Ninety-six per cent were intermediate and 1% susceptible to erythromycin, 97%
      susceptible to tetracycline, and 89% susceptible to trimethoprim. Only one
      isolate showed resistance to ciprofloxacin. H. influenzae from sputum were more
      likely to be susceptible than isolates from other sources. Of 845 M. catarrhalis,
      92% produced beta-lactamase and 9% were susceptible to ampicillin, >99% were
      susceptible to co-amoxiclav, cefotaxime, erythromycin and fluoroquinolones.
      CONCLUSIONS: Clinically relevant demographic factors predictive of susceptibility
      were country and patient age in S. pneumoniae, and specimen type (sputum/non
      sputum) in H. influenzae. Susceptibility to most antimicrobials remains high in
      Ireland and very high in Great Britain.

PMID- 14585866
TI  - Issues to debate on the Women's Health Initiative (WHI) study. Epidemiology or
      randomized clinical trials--time out for hormone replacement therapy studies?
AB  - Over the last 40 years, there has been increasing epidemiological evidence that
      post-menopausal treatment with sex steroids in physiological doses may reduce the
      relative risk of cardiovascular disease (CVD). These findings have been supported
      by biological studies showing favourable changes in cardiovascular risk factors
      with estrogen supplementation. The impact of the so-called 'healthy user' bias
      has been eagerly debated, and the results of the first and only randomized long
      term clinical trial of HRT for primary prevention have therefore been long
      awaited. The dramatic decision to halt the Women's Health Initiative (WHI) study
      before completion came unexpectedly as the consequence of not only an increased
      risk of breast cancer but also increased occurrence of cardiovascular events with
      HRT. Due to the superior design of the study, the results from the WHI study have
      had an enormous impact on the clinical recommendations of HRT to post-menopausal
      women, concurrent with a degradation of evidence from observational studies. It
      is not very likely that other long-term randomized clinical trials (RCTs) will be
      completed and epidemiology has certainly been disreputed-so is this 'time out'
      for HRT studies?

PMID- 14585867
TI  - Issues to debate on the Women's Health Initiative (WHI) study. Prescription
      attitudes among Belgian gynaecologists after premature discontinuation of the WHI
      study.
AB  - BACKGROUND: A survey was conducted in order to assess the attitude of Belgian
      practitioners toward HRT, after publication of the results of the 'Women's Health
      Initiative' (WHI) study. METHODS: Using a single case of a 55-year-old woman (no
      particular medical history, no longer climacteric symptoms), eight clinical case
      records were constructed by modifying three variables: (i) the HRT type [either
      conjugated estrogens (CEE) 0.625 mg + medroxyprogesterone acetate (MPA) or
      tibolone 2.5 mg]; (ii) the HRT duration (2 years or 11 years); and (iii) the bone
      density result (T-score +0.5 or -1.5). One case (drawn at random) was sent to
      Belgian gynaecologists (n = 1374), who were asked whether they would pursue,
      discontinue or modify the HRT regimen. RESULTS: In total, 577 returns were
      obtained (42% response rate). Globally, 19.8% of the physicians would stop
      prescribing the CEE+MPA regimen, 19.5% would continue the same regimen, and 60.7%
      would prescribe another HRT type, while respectively 15.9% of them would
      discontinue tibolone, 76.1% would continue it and 8% would prescribe another
      regimen (P < 0.001). After 2 years of use, 11.7% would discontinue HRT, while
      23.5% would do so after 11 years (P < 0.001). No differences in prescription
      rates or discontinuation rates were observed in relation to the bone density
      results. CONCLUSIONS: The results of this survey suggested that Belgian
      gynaecologists intend to continue prescribing HRT, despite the negative findings
      of the WHI study. When patients are using tibolone, physicians generally maintain
      the same regimen, but when using CEE+MPA physicians tend to prescribe another HRT
      regimen. Less than 25% of physicians will spontaneously discontinue HRT, even
      after 11 years of use.

PMID- 14585868
TI  - Failure of oocyte maturation: possible mechanisms for oocyte maturation arrest.
AB  - For human IVF, the patient's ovaries are hormonally stimulated to ensure the
      collection of fully matured oocytes that are at the metaphase II stage. Only
      these oocytes can be successfully fertilized either when mixed with sperm or
      after ICSI. Nevertheless, in some cases immature or maturing oocytes are
      recovered from follicles. Surprisingly, sometimes these oocytes do not complete
      maturation when cultured in vitro, for unknown reasons. In this article we
      discuss some possible mechanisms that may be responsible for those atypical
      arrests.

PMID- 14585869
TI  - An ethical approach to giving couples information about their fetus.
AB  - The amount of information available to couples about the health of their fetus is
      increasing. An important question in prenatal diagnosis is what information
      should be given to couples, and how best to present it. It has been argued
      elsewhere that, in the absence of economic constraints on testing, there is no
      place for limiting the information available to couples about their fetus.
      However, not every couple wants all available information, and it is not always
      clear what couples do want to know. Providing unwanted information about the
      health of a fetus may be harmful in a number of ways. Herein, the potential harms
      of being given unwanted information about one's fetus are illustrated by using
      case studies drawn from clinical practice, and a new approach to prenatal
      diagnosis is suggested. If the harms of being given unwanted information about
      one's fetus are to be avoided, then couples need an opportunity to limit the data
      gathered about their fetus at prenatal diagnosis.

PMID- 14585870
TI  - Controlled ovulation of the dominant follicle: a critical role for LH in the late
      follicular phase of the menstrual cycle.
AB  - BACKGROUND: A method was sought to control ovulation of the dominant follicle and
      to test the importance of LH during the late follicular phase of the menstrual
      cycle. Menstrual cycles of rhesus monkeys were monitored, and treatment initiated
      at the late follicular phase (after dominant follicle selection, before
      ovulation). METHODS: The 2-day treatment consisted of GnRH antagonist plus either
      r-hFSH and r-hLH (1:1 or 2:1 dose ratio) or r-hFSH alone. In addition, half of
      the females received an ovulatory bolus of hCG. RESULTS: When treatment was
      initiated at estradiol levels >120 pg/ml, neither the endogenous LH surge,
      ovulation nor luteal function were controlled. However, when treatment was
      initiated at estradiol levels 80-120 pg/ml using either 1:1 or 2:1 dose ratios of
      FSH:LH, the LH surge was prevented, and ovulation occurred following hCG
      treatment. FSH-only treatment also prevented the LH surge, but follicle
      development appeared abnormal, and hCG failed to stimulate ovulation.
      CONCLUSIONS: Control over the naturally dominant follicle is possible during the
      late follicular phase using an abbreviated GnRH antagonist, FSH+LH protocol. This
      method offers a model to investigate periovulatory events and their regulation by
      gonadotrophins/local factors during the natural menstrual cycle in primates.

PMID- 14585871
TI  - Increased mRNA expression of vascular endothelial growth factor and its receptor
      (flt-1) in the hydrosalpinx.
AB  - BACKGROUND: The adverse effects of hydrosalpinx on the outcomes of IVF have been
      well documented, but the mechanisms of hydrosalpinx fluid formation remain
      unclear. This study compares the mRNA expression of vascular endothelial growth
      factor (VEGF) and its receptors (KDR and flt-1) in the hydrosalpinx with that in
      the healthy oviduct. METHODS: Oviduct tissue was collected from 10 infertile
      women with hydrosalpinx and 10 parous women with healthy oviduct. The mRNA
      expression of VEGF and its receptors in isolated oviduct epithelial cells were
      analysed using semi-quantitative reverse-transcriptase PCR. RESULTS: mRNA
      expression of VEGF and its receptor flt-1 in the hydrosalpinx was significantly
      higher than that in the healthy oviduct, but no significant difference was
      demonstrated for the KDR receptor. CONCLUSIONS: This study supports the notion
      that VEGF may play an important role in the hydrosalpinx fluid formation,
      possibly by promoting vascular and epithelial permeability and therefore serum
      transudation.

PMID- 14585872
TI  - Antioxidants and reactive oxygen species in follicular fluid of women undergoing
      IVF: relationship to outcome.
AB  - BACKGROUND: The role of free radicals and reactive oxygen species (ROS) in female
      reproductive function is still unclear. The present study was designed to
      investigate their relationship with ovulation, fertilization and conception.
      METHODS: Follicular aspirates obtained from women undergoing IVF following
      controlled ovarian stimulation were evaluated using the ferric reducing
      antioxidant power (FRAP) assay for baseline total antioxidant capacity (TAC).
      Both the baseline TAC and the decline in TAC over 72 h (two-point assay) were
      used as markers of oxygen radical activity. RESULTS: A total of 303 follicular
      aspirates from 63 women were analysed. Two hundred and eighteen (71.9%) yielded
      oocytes, 169 (77.5%) of these fertilized and 134 (79.3%) of these embryos
      survived until the time of embryo transfer. Baseline TAC was no different in
      follicular fluid whether the follicle contained an oocyte or not, but was
      significantly higher in fluid from follicles whose oocyte successfully fertilized
      and significantly lower in fluid from follicles where the resultant embryo
      survived to transfer. The decline in TAC was lower when the oocytes fertilized
      and higher in association with embryo viability, but the differences were not
      statistically significant. CONCLUSIONS: These results provide further evidence
      that ROS play a role in female reproductive function.

PMID- 14585873
TI  - A prospective randomized clinical trial comparing an individual dose of
      recombinant FSH based on predictive factors versus a 'standard' dose of 150
      IU/day in 'standard' patients undergoing IVF/ICSI treatment.
AB  - BACKGROUND: The study aim was to compare the use of individual rFSH doses between
      100 and 250 IU/day (calculated using the rFSH dose normogram) with a standard
      dose of rFSH of 150 IU/day. METHODS: This prospective randomized dual-centre
      clinical trial included 267 first IVF/ICSI cycles using the long agonist protocol
      in 'standard' patients. Following down-regulation, 262 patients were randomized
      using computer-generated lists using 'clusters of 10' into the individual dose
      (study) group (n = 131) or the standard dose (control) group (n = 131). RESULTS:
      In the study group, 101 patients (77.1%) had an appropriate response (defined as
      5-14 oocytes), compared with 86 (65.6%) in the control group (P < 0.05). Fewer
      than five oocytes were retrieved in two patients (1.5%) in the study group,
      compared with 14 patients (10.7%) in the control group (P < 0.05). By comparison,
      >14 oocytes were retrieved from 27 patients (20.6%) in the study group and from
      26 (19.8%) control patients (P = NS). Eighty-six per cent of the individual dose
      patients did not require any dose adjustment on day 8, compared with 45% of the
      standard dose patients (P < 0.01). The ongoing pregnancy rate per initiated cycle
      was 36.6% in the study group and 24.4% in the control group (P < 0.01). One
      patient (0.8%) in the study group, and four patients (3.1%) in the control group,
      were hospitalized due to ovarian hyperstimulation syndrome. CONCLUSIONS: An
      individual dose regimen in a well-defined 'standard' patient population increased
      the proportion of appropriate ovarian responses and decreased the need for dose
      adjustments during controlled ovarian stimulation. A higher ongoing pregnancy
      rate was observed in the individual dose group.

PMID- 14585874
TI  - Intravenous albumin does not prevent moderate-severe ovarian hyperstimulation
      syndrome in high-risk IVF patients: a randomized controlled study.
AB  - BACKGROUND: Intravenous albumin administration has been described for many years
      as a debatable, but probably useful preventive measure in ovarian
      hyperstimulation syndrome (OHSS). The present study details the largest
      randomized controlled trial to date of albumin infusion versus no treatment in
      IVF patients with a high risk of developing moderate to severe OHSS. METHODS:
      Between March 1999 and February 2002, women undergoing IVF at the IVI Valencia
      with >20 retrieved oocytes were included. A total of 988 patients was initially
      enrolled. Immediately after oocyte retrieval, patients were allocated to two
      groups based on a computer randomization: the first group received 40 g human
      albumin; the second group received no treatment. Subjects were weighed and a
      blood analysis performed immediately after oocyte retrieval and again 7 days
      later. Women were monitored on an outpatient basis until menstruation, or until
      fetal heart activity was detected. Twelve subjects were excluded due to follow-up
      loss, leaving 976 women (377 of them oocyte donors), with 488 in each group.
      RESULTS: No difference was found between the two groups in terms of patient
      characteristics and outcome. Moderate-severe and severe-only OHSS rates were
      similar. The incidence of haemoconcentration and liver and renal dysfunction at 7
      days after oocyte retrieval was similar in the two groups. In women who developed
      moderate/severe (n = 66) or only severe (n = 46) OHSS, there was no difference
      based on prior albumin administration between blood parameters or body weight on
      the day of oocyte retrieval, 7 days later, and even when comparing variation
      between both measurements. Moreover, the number of patients with paracentesis,
      hospital admissions, complications and days of OHSS until resolution did not
      differ. CONCLUSIONS: Albumin infusion on the day of oocyte retrieval is not a
      useful means of preventing the development of moderate-severe OHSS.

PMID- 14585875
TI  - Difference in body weight between American and Italian women with polycystic
      ovary syndrome: influence of the diet.
AB  - BACKGROUND: The study aim was to determine differences in body mass in two
      populations of women (USA and Italy) with polycystic ovary syndrome (PCOS), and
      to assess the effect of diet on body mass and cardiovascular risk factors.
      METHODS: Pools of women with PCOS from the USA (n = 343) and Italy (n = 301),
      seen between 1993 and 2001, were available for assessment. From these
      populations, 20 women who were seen consecutively in 2001 at each site had
      detailed analyses of diet and cardiovascular risk factors. RESULTS: In the entire
      group, American women had a significantly higher body mass compared with Italian
      women (P < 0.01). Also, the 20 women consecutively evaluated in the USA had a
      significantly higher mean (+/- SD) body mass index (40.3 +/- 1.0 kg/m(2)) than in
      Italy (29.7 +/- 1.0 kg/m(2)). US women had worse insulin resistance, lower levels
      of high-density lipoprotein-cholesterol (HDL-C) (P < 0.01) and higher levels of
      triglycerides (P < 0.01). Dietary analysis in the two groups indicated that the
      total daily calorific intake was similar (USA 2277 +/- 109; Italy 2325 +/- 68
      Kcal), with no appreciable differences in dietary content of protein,
      carbohydrate and fat. However, the dietary saturated fat content was
      significantly higher in US women (31.9 +/- 3 versus 18.2 +/- 2 g/day, P < 0.01).
      Saturated fat intake correlated negatively with HDL-C (P < 0.01). CONCLUSIONS:
      Among women with PCOS, body mass was significantly higher in US women compared
      with Italian women. However, total calorie intake and dietary constituents were
      similar, except for a higher saturated fat in US women. It is hypothesized that
      diet alone does not explain differences in body mass; genetic and lifestyle
      factors likely contribute. An increased saturated fat intake may worsen the
      cardiovascular risk profile.

PMID- 14585876
TI  - Bioavailability of hCG after intramuscular or subcutaneous injection in obese and
      non-obese women.
AB  - BACKGROUND: Obese women require higher gonadotrophin doses for ovarian
      stimulation and to trigger ovulation. The bioavailability of a drug is affected
      by its route of administration. Herein, the bioavailability of hCG was compared
      after intramuscular (i.m.) or subcutaneous (s.c.) injection in obese and non
      obese women. METHODS: Twenty four Chinese women, 12 with a body mass index (BMI)
      >/==" BORDER="0">28 kg/m(2) and 12 with a BMI of 20-25 kg/m(2) were recruited as
      the obese and non-obese groups respectively. A single hCG injection was given
      intramuscularly on one occasion, and subcutaneously on a second occasion,
      separated by 4 weeks. Blood samples were taken at intervals for the
      pharmacokinetic study of hCG. RESULTS: Examination of the hCG plasma
      concentration-time curve showed the area under the curve (AUC) and maximum
      concentration (C(max)) of hCG to be significantly higher after i.m. injection
      than after s.c. injection in both the obese and non-obese groups. However, the
      AUC and C(max) values in obese women were significantly lower than in non-obese
      women, irrespective of whether i.m. or s.c. dosing was employed. CONCLUSIONS:
      Intramuscular dosing of hCG provided better bioavailability than s.c. dosing, but
      bioavailability was significantly less in obese women than in non-obese women.

PMID- 14585877
TI  - Cytogenetic and molecular study of a premature male infant with 46,XX derived
      from ICSI: case report.
AB  - We investigated the aetiology of the male phenotype in a premature infant derived
      from ICSI with a 46,XX karyotype. A karyotypically normal couple underwent ICSI
      because of obstructive azoospermia in the male partner. Sperm were retrieved by
      testicular sperm extraction (TESE), cryopreserved, and later used for ICSI. The
      pregnancy after ICSI ended at 20 weeks. A normal-appearing male was delivered but
      he did not survive. Umbilical cord blood and placenta were sampled and used for
      molecular and cytogenetic investigation. The 46,XX karyotype from G-banding in
      this male infant correlated to a balanced female comparative genomic
      hybridization (CGH) profile in placental tissue. No PCR amplification of SRY on
      the p arm of the Y chromosome was observed while fluorescence in-situ
      hybridization (FISH) with the SRY probe also could not detect the gene in cord
      blood or placental tissues. CGH and FISH, with X and Y centromeric probes, failed
      to detect mosaicism in the trophoblast, stroma and amnion. Skewed X-chromosome
      inactivation (81%) was found in the chorionic villi. The molecular and
      cytogenetic studies indicated a 46,XX male infant without the SRY gene or
      46,XX/XY mosaicism. The possible mechanism in this SRY-negative XX male by ICSI
      is discussed.

PMID- 14585878
TI  - 10, 15 reciprocal translocation in an infertile man: ultrastructural and
      fluorescence in-situ hybridization sperm study: case report.
AB  - BACKGROUND: Peculiar sperm defects are described in a sterile man heterozygous
      for a balanced translocation t(10;15) (q26;q12). As this structural
      reorganization was absent in the parents, the translocation must have appeared de
      novo in the present patient. METHODS: Spermatozoa were analysed under light and
      transmission electron microscopy (TEM). Fluorescence in-situ hybridization (FISH)
      was performed on the lymphocyte karyotype. Aneuploidy frequencies of chromosomes
      18, X and Y in sperm nuclei, not involved in the translocation, were investigated
      using three-colour FISH. Dual- colour FISH was used to evaluate segregation of
      chromosomes 10, 15 in decondensed sperm nuclei. Moreover, three-colour FISH,
      using telomeric probes for chromosomes 10, 15 was performed in order to
      distinguish balanced and unbalanced gametes. RESULTS AND CONCLUSIONS: Overall,
      structural characteristics indicate general immaturity of the germinal cells.
      FISH sperm analysis detected an increase in chromosome 18 disomy (0.81%)
      suggesting an interchromosomal effect. A high frequency of diploidies,
      particularly 18,18,X,X and 18,18,X,Y, was also found. FISH segregation analysis
      for chromosomes 10, 15 indicated that 32.8% were balanced gametes, whereas 68.2%
      were unbalanced. Taken together, these data demonstrate in a male carrier of a
      reciprocal translocation t(10;15) the presence of diffuse ultrastructural sperm
      alterations and a high frequency of sperm aneuploidies. The existence of a
      correlation among these factors is proposed.

PMID- 14585879
TI  - Interleukin-1B (IL-1B) and interleukin-1 receptor antagonist (IL-1RN) gene
      polymorphisms are not associated with tubal pathology and Chlamydia trachomatis
      related tubal factor subfertility.
AB  - BACKGROUND: Chlamydia trachomatis infections have been associated with tubal
      pathology. However, not all C.trachomatis-infected women actually develop tubal
      pathology. Recently, host genetic factors such as the interleukin-1 gene cluster
      have been linked to inflammatory and infectious diseases. METHODS: Dutch
      Caucasian women were investigated for (i) the role of interleukin-1B (IL-1B) and
      interleukin-1 receptor antagonist (IL-1RN) gene polymorphisms in tubal pathology
      (group 1); and (ii) the presence of these gene polymorphisms in C.trachomatis IgG
      positive women with and without tubal pathology (group 2). Group 1 consisted of
      women with (n = 40) or without (n = 95) tubal pathology, respectively, and group
      2 of C.trachomatis IgG-positive women of whom 28 had tubal pathology at
      laparoscopy and 47 did not. IL-1B-511 and IL-1B+3954 gene polymorphisms were
      assessed by PCR-restriction fragment length polymorphism (RFLP), and the variable
      number of tandem repeats (VNTR) of the IL-1RN gene were assessed by a PCR-based
      assay. RESULTS: Neither IL-1B-511, IL-1B+3954 nor IL-1RN genotypes, allele or
      carrier frequencies showed significant association with tubal pathology or
      C.trachomatis post-infection-based tubal pathology. CONCLUSIONS: The data
      obtained suggest that specific IL-1 gene polymorphisms are not associated with
      the tubal pathology risk or to the development of C.trachomatis-based post
      infectious severe sequelae.

PMID- 14585880
TI  - A prospective, randomized, placebo-controlled trial on the use of mifepristone
      with sublingual or vaginal misoprostol for medical abortions of less than 9 weeks
      gestation.
AB  - BACKGROUND: A combination of mifepristone and misoprostol provides an effective
      method of medical abortion for early pregnancy. This is the first randomized
      trial comparing the use of sublingual misoprostol with vaginal misoprostol in
      combination with mifepristone for termination of early pregnancies up to 63 days.
      METHODS: A total of 224 women who requested legal termination of pregnancy up to
      63 days were randomized by computer- generated list into two groups and given 200
      mg of oral mifepristone followed 48 h later by either 800 micro g of sublingual
      (n = 112) or vaginal (n = 112) misoprostol. RESULTS: Complete abortion occurred
      in 98.2% (95% CI: 93-99) of women in the sublingual group and 93.8% (95% CI: 88
      97) in the vaginal group. There were three ongoing pregnancies in the vaginal
      group but none in the sublingual group. The median duration of vaginal bleeding
      was 17 days. There was no serious complication. Fever, chills and
      gastrointestinal side-effects (nausea, vomiting and diarrhoea) were significantly
      more common in the sublingual group. CONCLUSIONS: The combination of mifepristone
      and misoprostol is effective for medical abortion up to 63 days. Both the
      sublingual and vaginal are effective routes of administration. Further randomized
      trials are required to find out the optimal dose of sublingual misoprostol that
      can give the highest complete abortion rate and lowest incidence of side-effects.

PMID- 14585881
TI  - Effectiveness and mechanism of action of desmopressin in the treatment of copper
      intrauterine device-related menorrhagia: a pilot study.
AB  - BACKGROUND: Desmopressin, a synthetic analogue of the natural hormone
      vasopressin, stimulates endogenous haemostasis and exerts a powerful myometrial
      and vasoconstrictor action in a variety of pharmacological preparations. Both
      mechanisms of action may have therapeutic value for the treatment of intrauterine
      device (IUD)-related menorrhagia, which is believed to be caused not only by
      altered local haemostasis but also-according to a new hypothesis-by decreased
      vascular uterine resistance. The aim of this prospective study was to evaluate
      the effect of vasopressin drug on menstrual blood loss and on changes, if any, in
      uterine flow impedance. Mefenamic acid, which is commonly used to treat IUD
      related menorrhagia, was administered as a comparison. METHODS: Twenty-four women
      with IUD-induced menorrhagia were recruited and randomly allocated to treatment
      with either desmopressin or mefenamic acid. Menstrual blood loss (measured by
      pictorial blood loss assessment chart) and uterine artery resistance (measured
      with transvaginal colour Doppler) performed in two pretreatment periods were
      compared with 3-month treatment periods. RESULTS: Menstrual blood loss was
      significantly reduced in both treatment groups. In the desmopressin group, the
      effect was clinically useful in all subjects, but in the mefenamic group
      menstrual blood loss was consistently menorrhagic in two patients. No significant
      differences were observed in the uterine artery pulsatility index before and
      during treatment. CONCLUSIONS: Desmopressin may be a useful therapeutic tool for
      many women with IUD-related menorrhagia. Its mechanism of action lies in an
      ability to enhance local haemostasis, without affecting uterine blood flow.

PMID- 14585882
TI  - The value of transvaginal ultrasound to monitor the position of an intrauterine
      device after insertion. A technology assessment study.
AB  - BACKGROUND: The intrauterine device (IUD) is an effective contraceptive method.
      The contraceptive power as well as the side-effects of IUD are thought to relate
      to the position of the IUD in the uterine cavity. We assessed the accuracy of
      clinical evaluation of IUD position. METHODS: A prospective comparative study was
      performed. The clinical evaluation was compared with the TVU measurement of IUD
      position both immediately after insertion and 6 weeks after insertion. The
      primary outcome measures were the positive and negative predictive values (PPV
      and NPV) of the clinical evaluation of IUD position. RESULTS: 195 women were
      included consecutively, 181 women (92.8%) were available for follow-up. The PPV
      and NPV of clinical evaluation of IUD position immediately after insertion were
      respectively 0.60 (95% CI: 0.39-0.81) and 0.98 (95% CI: 0.96-1.0). The prevalence
      of an abnormally positioned IUD was 7.7% (95% CI: 3.9-11.4). The PPV and NPV of
      the clinical evaluation at follow-up were respectively 0.54 (95% CI: 0.26-0.81)
      and 1.0 (95% CI: 0.98-1.0). The prevalence of abnormal position was 4.0% (95% CI:
      1.7-7.1). CONCLUSION: Clinical evaluation is an excellent test for the evaluation
      of the position of an IUD and routine TVU is not indicated for this purpose.

PMID- 14585883
TI  - Growth, psychomotor development and morbidity up to 3 years of age in children
      born after IVF.
AB  - BACKGROUND: To examine the long-term child outcome after IVF until the age of 3
      years in Northern Finland, we conducted a population-based cohort study. METHODS:
      First, a cohort of 299 IVF children born in 1990-1995 was compared with a cohort
      of 558 controls representing the general population in terms of a multiple birth
      rate of 1.2%, randomly chosen from the Finnish Medical Birth Register (FMBR) and
      matched for sex, year of birth, area of residence, parity, maternal age and
      social class (full sample analyses). Second, IVF singletons (n = 150) were
      compared with singleton controls (n = 280). Third, a plurality matched control
      cohort (n = 100) for IVF twins (n = 100) was randomly chosen, matched as above,
      from the FMBR and analysed separately. Infant mortality rate was compared with
      the national rate from the FMBR. RESULTS: Infant mortality in the IVF group was
      >2-fold higher compared to the national rate in the general population. The risk
      (OR, 95% CI) of low weight and height, below the lowest quartile, at 1 year of
      age (1.6, 1.1-2.2; 1.6, 1.1-2.4) and 2 years of age (1.5, 1.1-2.4; 1.7, 1.2-2.5)
      was significantly higher in the IVF group when compared with the general
      population control group. No statistically significant differences were found in
      the psychomotor development between the cohorts. Cumulative incidence of
      different diseases up to 3 years of age was significantly higher among IVF
      children in the full sample and singleton analyses (OR, 95% CI: 2.3, 1.7-3.2;
      2.1, 1.3-3.3 respectively) especially regarding respiratory diseases (3.5, 1.9
      6.5; 3.1, 1.0-9.4) and diarrhoea (3.7, 2.2-6.2; 5.7, 2.6-12.7), but not in twin
      comparisons. CONCLUSIONS: The growth of IVF children was behind that of control
      children during the first 3 years of life, but their psychomotor development was
      similar. Their postnatal health was worse, probably reflecting the problems in
      the neonatal period.

PMID- 14585884
TI  - The effect of endometrial thickness on IVF/ICSI outcome.
AB  - BACKGROUND: During the menstrual cycle the endometrium undergoes cyclic
      proliferative and secretory changes in preparation for implantation. If this
      preparation is not sufficient, then implantation will fail. The impact of
      endometrial thickness on the day of embryo transfer on IVF outcome was
      investigated in the present study. METHODS: A retrospective analysis was
      conducted of 1228 IVF/ICSI cycles. Stimulation was with clomiphene citrate (CC) +
      hMG in one-third of the cycles, and ultrashort GnRH agonist stimulation in two
      thirds. Cycle parameters were compared between pregnant and non-pregnant
      patients. A similar comparison was made between ongoing pregnancies and those
      that resulted in a loss. RESULTS: There were more follicles, oocytes and embryos,
      the endometrium was thicker and the embryo quality was higher among women who
      became pregnant when compared with non-pregnant women after assisted
      reproduction. The pregnancy rate improved as endometrial thickness increased. No
      difference in cycle parameters and endometrial thickness was found between
      ongoing pregnancies and pregnancies that resulted in a first-trimester loss. CC
      had no measurable adverse endometrial effect, but the pregnancy rate was lower in
      CC+hMG cycles. CONCLUSIONS: Increased endometrial thickness is associated with
      higher pregnancy rates. However, neither attainment of pregnancy nor pregnancy
      outcome was predicted by endometrial thickness alone.

PMID- 14585885
TI  - Hepatitis C virus detection in follicular fluid and culture media from HCV+
      women, and viral risk during IVF procedures.
AB  - BACKGROUND: Hepatitis C virus (HCV) has been detected in sperm, but no data are
      available on follicular fluid (FF) collected on IVF procedures. The aim of this
      study was to: (i) search for HCV RNA in FF and in culture media at each step of
      IVF undergone by HCV(+) women; (ii) investigate the impact of blood contamination
      of FF induced by vascular injury associated with transvaginal ovarian puncture;
      (iii) assess risk for the embryo and the impact on the contamination rate of the
      newborn; and (iv) determine the viral risk presented by these fluids in order to
      define guidelines for the laboratory. METHODS: FF from 22 IVF procedures
      performed in 17 HCV(+) women were classified as either clear, lightly bloody or
      bloody FF. Oocytes from each FF were washed and incubated in separated
      fertilization media. At 20 h after puncture (day 1), the fertilized oocytes were
      washed and transferred to fresh media until embryo transfer. HCV RNA was detected
      and quantified in FF and media using Cobas Amplicor and Cobas Monitor HCV RNA
      kits. RESULTS: HCV RNA was positive in 39 of 44 FF samples, and viral loads
      increased with blood contamination. At day 1, after rinsing of oocyte-cumulus
      complexes, only 8 of 44 media were still positive. Viral loads were quantified in
      5 of 8 positive media, were below the test sensitivity threshold in 4 of 5 HCV
      RNA-positive media, and just above it in the fifth medium. The day of transfer
      HCV RNA was undetectable in all media. CONCLUSIONS: HCV RNA was detected in 89%
      of FF irrespective of the degree of blood contamination, and in 25% of the media
      at day 1. FF must be considered as potentially infected. Blood contamination
      increases HCV load in the FF. Rinsing oocytes seems significantly to discard the
      HCV RNA. It is too early to assess the impact of IVF on the contamination rate of
      HCV mothers' offspring. After counselling, attempting IVF in HCV(+) women is
      justified. Universal guidelines prevent nosocomial infection, and IVF does not
      specifically increase the professional risk.

PMID- 14585886
TI  - Can history, ultrasound, or ELISA chlamydial antibodies, alone or in combination,
      predict tubal factor infertility in subfertile women?
AB  - BACKGROUND: This study aimed to determine whether medical history, transvaginal
      ultrasound (TVU) or Chlamydia trachomatis antibody testing (CAT), alone or in
      combination, could provide a non-invasive, clinically useful screening test for
      predicting tubal factor infertility (TFI) in subfertile women. METHODS: Prior to
      tubal evaluation, relevant medical history, TVU findings, and enzyme-linked
      immunosorbent assay (ELISA) IgG CAT results were collected. Sensitivity,
      specificity, likelihood ratios (LR) and accuracy for predicting TFI, as
      determined by laparoscopy and dye hydrotubation, were calculated for each test
      alone, and in parallel and series combination. RESULTS: Thirty per cent (63/207)
      were diagnosed with TFI. The highest sensitivity (67%, 95% CI: 54-77) included
      any positive test, yet missed one in three women with TFI. The highest
      specificity (100%, 95% CI: 97-100) required all three tests positive, but
      identified only three women. Only the combination of CAT and TVU rated as a good
      clinical test, but confidence intervals were wide due to the small numbers
      affected. The combination of CAT or TVU and CAT alone reported the highest
      accuracy (73%, 95% CI: 66-78), misdiagnosing one in four women. CONCLUSION:
      Medical history, TVU appearances, and ELISA IgG CAT alone, or in combination,
      failed to predict accurately TFI in subfertile women.

PMID- 14585887
TI  - High singleton live birth rate following classical ovulation induction in
      normogonadotrophic anovulatory infertility (WHO 2).
AB  - BACKGROUND: Medical induction of ovulation using clomiphene citrate (CC) as first
      line and exogenous gonadotrophins as second line forms the classical treatment
      algorithm in normogonadotrophic anovulatory infertility. Because the chances of
      success following classical ovulation induction are not well established, a shift
      in first-line therapy can be observed towards alternative treatment. The study
      aim was to: (i) reliably assess the probability of singleton live birth following
      classical induction of ovulation; and (ii) construct a prediction model, based on
      individual patient characteristics assessed upon standardized initial screening,
      to help identify patients with poor chances of success. METHODS: A total of 240
      consecutive women visiting a specialist academic fertility unit with a history of
      infertility, oligomenorrhoea or amenorrhoea, and normal FSH and estradiol serum
      concentrations (WHO group 2) was prospectively followed. The women had not been
      previously treated with ovulation-inducing agents. All patients commenced with
      CC. Patients who did not ovulate within three treatment cycles of incremental
      daily doses up to 150 mg for 5 consecutive days or ovulatory CC patients who did
      not conceive within six cycles, subsequently underwent gonadotrophin induction of
      ovulation applying a step-down dose regimen. The main outcome measure was
      pregnancy resulting in singleton live birth. Cox regression was used to construct
      a multivariable prediction model. RESULTS: Overall, there were 134 pregnancies
      ending in a singleton live birth (56% of women). The cumulative pregnancy rate
      after 12 and 24 months of follow-up was 50% and 71% respectively. Polycystic
      ovary syndrome (PCOS) patients (49%), clearly non-PCOS patients (13%) and the in
      between group did not differ in prognosis (P = 0.9). The multivariable Cox
      regression model contained the woman's age, the insulin:glucose ratio and
      duration of infertility. With a cut-off value of 30% for low chance, the model
      predicted probabilities at 12 months lower than this cut-off for 25 out of 240
      patients (10.4%). CONCLUSIONS: Classical ovulation induction produces very good
      results in normogonadotrophic anovulatory infertility. Alternative treatment
      options may not be indicated as first-line therapy in these patients, except for
      subgroups with poor prognosis. These women can be identified by older age, longer
      duration of infertility and higher insulin:glucose ratio.

PMID- 14585888
TI  - Does egg-sharing compromise the chance of donors or recipients achieving a live
      birth?
AB  - BACKGROUND: To evaluate the effect of egg-sharing and the outcome of assisted
      reproductive treatment (ART) in standard IVF/ICSI patients, egg-sharing donors
      and egg-sharing recipients. METHODS: Descriptive cohort study to evaluate 276 egg
      sharing cycles involving 192 egg-sharers, 274 recipient cycles receiving eggs
      from egg-sharers and 1098 non-egg-sharing standard IVF/ICSI cycles from January
      1998 to December 2002. Patients were divided into three groups: group A, egg
      sharers; group B, non-egg-sharers, age <36 years, FSH <10 IU/l, BMI <30 kg/m(2);
      and group C, egg-sharing recipients, all ages. Duration and amount of
      gonadotrophin required to achieve follicular maturity, number of eggs collected
      and donated, fertilization rate, pregnancy rates and live birth rates were
      compared between donor, recipient and standard IVF/ICSI patients. The chi(2 )test
      was used to test for statistical significance (P < 0.05). RESULTS: There was no
      significant difference in pregnancy rate and live birth rate of egg-sharers,
      group A (42.0%, 33.0%), non-egg-sharers, group B (40.0%, 30.9%) and recipients,
      group C (41.4%, 28.6%). The number of oocytes collected, number of mature
      follicles and amount of gonadotrophin used was not significantly different
      between the two groups (A and B). The average number of embryos transferred and
      the mean number of eggs allocated between egg-sharers and recipients was not
      statistically different. CONCLUSION: Egg-sharing does not compromise the chance
      of achieving a pregnancy or live birth for the egg-sharer or the recipient as
      compared to standard IVF/ICSI patients. The egg-sharers were not at a higher
      potential risk of ovarian stimulation syndrome and there was no imbalance of egg
      allocation.

PMID- 14585889
TI  - Depletion of ovarian reserve in young women after treatment for cancer in
      childhood: detection by anti-Mullerian hormone, inhibin B and ovarian ultrasound.
AB  - BACKGROUND: Treatment of cancer during childhood may result in loss of primordial
      follicles from the ovary. METHODS: Ten cancer survivors and 11 controls with
      regular menstrual cycles, in addition to 10 cancer survivors and 10 controls
      taking the combined oral contraceptive pill (COCP) were recruited. Subjects were
      investigated on days 3-5 of a menstrual cycle, or week 3 of COCP administration
      before and 24 h after administration of 225 IU FSH. RESULTS: Serum FSH levels
      were elevated in cancer survivors with regular menstrual cycles (7.5 +/- 1.4
      versus 4.2 +/- 0.3 IU/l; P = 0.02), while anti-Mullerian hormone (AMH) levels
      were lower (13.0 +/- 3.0 versus 21.0 +/- 3.4 pmol/l; P < 0.05). Other hormone
      levels were unchanged. Ovarian volume was smaller in cancer survivors than
      controls (3.0 +/- 0.5 versus 5.0 +/- 0.8 ml; P < 0.05), but antral follicle count
      (AFC) was similar. During COCP administration, inhibin B remained undetectable in
      six cancer survivors after FSH administration, whereas all controls showed a rise
      in inhibin B levels. The AFC was lower in cancer survivors than in controls (4.2
      +/- 0.8 versus 7.2 +/- 0.8; P = 0.02). Ovarian volume was low in both groups, but
      did not differ between them. CONCLUSIONS: The study results demonstrate both
      hormonal and biophysical evidence of partial loss of the ovarian reserve in young
      cancer survivors. This was detected both in women with normal menstrual cycles
      and during COCP administration.

PMID- 14585890
TI  - Thromboembolism after ovarian stimulation: successful management of a woman with
      superior sagittal sinus thrombosis after IVF and embryo transfer: case report.
AB  - The current literature was reviewed in order to analyse the clinical
      manifestations, progression and management, and pregnancy outcome of
      thromboembolism in infertile patients undergoing ovarian stimulation. The first
      case of superior sagittal sinus thrombosis following IVF that was successfully
      managed with intracranial thrombectomy is also reported. This retrospective
      cohort study comprised 65 women who experienced thromboembolism after ovarian
      stimulation (64 from other published studies and the present case report).
      Thrombosis attack occurred at a mean (+/-SD) of 25.5 +/- 20.1 days after oocyte
      retrieval. The onset timing in the intracranial thrombosis group (10.2 +/- 4.6
      days) was less (P < 0.05) than in those experiencing thromboembolism at other
      sites. Ovarian hyperstimulation syndrome (OHSS), haemoconcentration and high
      serum estradiol level were noted in 79, 62 and 54% of women respectively. Forty
      eight of 55 patients (87%) who received anticoagulation recovered without
      sequelae. Among patients willing to continue pregnancy, 32% succeeded in term
      delivery with all healthy babies, and 23% were ongoing pregnancies. In
      conclusion, ovarian stimulation cycles accompanying high serum estradiol levels,
      haemoconcentration or OHSS are at potential risk of thromboembolism. Dose
      adjusted heparinization is recommended as the first-line treatment of choice,
      while intravascular thrombolysis or operative thrombectomy is an aggressive but
      effective treatment. Continuation of pregnancy is considered safe, without any
      increased risk of fetal congenital anomalies.

PMID- 14585891
TI  - Low proportions of sperm can bind to the zona pellucida of human oocytes.
AB  - BACKGROUND: Sperm binding to the zona pellucida (ZP) is required for human
      fertilization. Under experimental conditions not limited by ZP binding sites, the
      cumulative numbers of sperm binding tightly to the ZP will asymptote with time to
      the total number of sperm in the insemination medium capable of binding. METHODS:
      Numbers of ZP-bound sperm were counted after groups of 10 oocytes were incubated
      with 2x10(4) motile sperm in 20 micro l droplets. The time-course of sperm
      binding was measured in three consecutive 2 h incubation periods using fresh
      oocytes for each period (n = 12). Using the kinetic theory of gases to model
      sperm-oocyte collision rates, the time-course results were extrapolated to give
      the total proportion of motile sperm capable of binding to the ZP. ZP binding of
      sperm after 4 h incubation was studied in 20 fertile and 20 normozoospermic
      subfertile men. RESULTS: The percentage of motile sperm capable of binding was
      for fertile men: mean 14% (range 8-25) and for the subfertile: 4.3% (range 0.1
      13, P < 0.001). Sperm morphology correlated with the proportion of ZP-bound
      sperm. CONCLUSIONS: More than 75% of motile sperm from fertile men have no
      ability to bind to the ZP. This finding has important implications for
      improvement of semen analysis.

PMID- 14585892
TI  - A modified method for ICSI in the pig: injection of head membrane-damaged sperm
      using a 3-4 micro m diameter injection pipette.
AB  - BACKGROUND: Conventional ICSI to date was focused only on tail membrane damage to
      achieve sperm immobilization and disruption of the plasma membrane, even though
      liberation of soluble sperm factors is achieved by disruption of the sperm head
      membrane. METHODS: A modified method for ICSI was developed: head membrane
      damaged spermatozoa aspirated tail or head first were injected into the ooplasm
      using a 3-4 micro m diameter injection pipette connected to an open-ended
      aspiration tube regulated by mouth. The efficiency of this modified ICSI was
      compared with that of conventional ICSI and IVF. RESULTS: When spermatozoa
      aspirated tail first were injected, a decondensed sperm head was more frequently
      observed in the oocyte cytoplasm with the modified ICSI (80.0%) than with
      conventional ICSI (55.7%) or IVF (63.5%) (P < 0.001). The rates of male
      pronucleus (MPN) formation in the modified ICSI or IVF were significantly higher
      (50.7 and 39.7%, respectively) than in conventional ICSI (27.9%) (P < 0.001). The
      rates of survival, cleavage and embryo development to blastocyst were
      significantly higher in the modified ICSI (71.7, 60.6 and 17.5%) than in
      conventional ICSI (48.1, 48.7 and 10.5%) (P < 0.001). No significant differences
      in MPN formation and embryo development to blastocyst were observed between the
      tail- and head-first sperm aspiration. CONCLUSION: Our results demonstrated that,
      in the pig, the procedures of pursuing, capturing and immobilizing a spermatozoon
      and producing deliberate damage to the tail membrane in conventional ICSI were
      not required in the modified ICSI. We believe that the present study provides
      sufficient technical advancement to replace conventional ICSI with the modified
      ICSI, which is more effective and also avoids unnecessary procedures involved in
      conventional ICSI.

PMID- 14585893
TI  - Meiotic spindle location and identification and its effect on embryonic cleavage
      plane and early development.
AB  - BACKGROUND: To examine the relationship between the meiotic spindle, the first
      cleavage plane and any resulting influence on embryonic development parameters.
      METHODS: Sibling oocytes (n = 246) were allocated to either a control [polar body
      (PB)-aligned] or a treatment (spindle-aligned) microinjection group by use of a
      random numbers table. Spindles were identified by PolScope((R)) and the early
      embryo development parameters, and angle of first cleavage plane in relation to a
      defined animal-vegetal pole were analysed. RESULTS: Most oocytes (92.7%) had a
      visible spindle at the time of microinjection; however, 62.6% of first PBs (1PBs)
      were not located above the spindle (average deviation 37.3 +/- 33.2 degrees;
      range 0-176.6), with 6.9% of 1PBs in the opposite hemisphere to the spindle. The
      second PBs (2PBs) can also have an unpredictable deviation from the position of
      the meiotic spindle (12.5 +/- 16.7 degrees; range 0-91.8). This increased when
      the 1PB was above the spindle, forming a physical barrier to extrusion (average
      24.7 +/- 16.1 degrees; range 7.9-91.8). Embryos developing from the spindle
      aligned microinjection group had significantly more blastomeres per embryo (P =
      0.044), a higher morphology score per embryo (P = 0.008) and a significantly
      higher average embryo score parameter (P = 0.003), with more embryos developing
      without any detectable fragmentation (P < 0.05) than the PB-aligned control
      group. Non-fragmented embryos undergo meridional cleavage, with a small angle
      between the spindle location and first cleavage plane (16.4 +/- 14.0 degrees )
      compared with embryos with some degree of fragmentation (P = 0.002). This angle
      increased with the degree of fragmentation, with worst quality embryos having a
      spindle:cleavage angle of 45.1 +/- 17.7 degrees. CONCLUSIONS: The 1PB and, to a
      lesser degree, the 2PB can be unreliable predictors of the exact meiotic spindle
      location in human oocytes. Embryos from spindle-aligned oocytes have an increase
      in all measured development parameters over control siblings. When the animal
      pole is defined as the meiotic spindle location, non-fragmented embryos tend to
      develop from a meridional cleavage; with the most fragmented embryos developing
      from a more equatorial initial cleavage plane. This study proposes that the
      spindle accurately marks the animal pole in human oocytes, and provides evidence
      linking the meiotic spindle location to the first cleavage plane and resulting
      early embryo development parameters in human embryos.

PMID- 14585894
TI  - Presence, but not type or degree of extension, of a cytoplasmic halo has a
      significant influence on preimplantation development and implantation behaviour.
AB  - BACKGROUND: Since there is considerable disagreement in grading cytoplasmic
      haloes, this prospective study was set up to evaluate if certain subtypes of
      haloes are related to further development. METHODS: Out of a total of 152
      patients, 713 zygotes could be checked for the formation of a halo. Where
      present, haloes were subdivided into concentric (symmetric) and polar
      (asymmetric) types. In addition, each halo was measured accurately to see if the
      extension of the halo might influence further development. In parallel,
      pronuclear patterns were checked. RESULTS: Halo-positive zygotes did not differ
      from halo-negative ones in terms of embryo quality and blastocyst formation rate.
      However, quality of blastocysts (assessed by their inner cell mass consistency)
      was significantly increased (P < 0.001) if a halo appeared at zygote stage. This
      phenomenon was not related to type of halo or degree of halo. In terms of
      pronuclear pattern, pattern 0 (0A, 0B) led to significantly more blastocysts (P <
      0.001) of better quality (P = 0.002) compared with patterns 1-5. A stepwise
      logistic regression showed no relationship between different halo types and
      pronuclear pattern 0. CONCLUSIONS: The present study indicates that any halo has
      a positive prognostic value on blastocyst quality, irrespective of the fact that
      it is light or extreme, polar or concentric. In addition, the developmental
      advantage of pattern 0 is confirmed.

PMID- 14585895
TI  - The effect of pronuclear morphology on early development and chromosomal
      abnormalities in cleavage-stage embryos.
AB  - BACKGROUND: Pronuclear (PN) zygote morphology has been proposed as a useful tool
      for selecting the best embryos for transfer. METHODS: PN morphology was recorded
      in 888 zygotes and classified according to similar/different PN size [groups A (n
      = 816) and B (n = 72)] and to the number, distribution and synchrony of nucleolar
      precursor bodies (NPB): subgroup I, pronuclei with 3-4 polarized NPB; subgroup
      II, 5-7 synchronic polarized NPB or 7-10 NPB distributed randomly; and subgroup
      III, morphologies other than those of groups I or II. Embryo development and
      chromosomal abnormalities were evaluated for each PN pattern. RESULTS: In
      patients aged </=37 years, the number of zygotes reaching morula and blastocyst
      stage was significantly (P = 0.0003) higher in group A than in group B. In group
      A, the incidence of chromosomal abnormalities was significantly (P = 0.0247)
      lower than in group B, and significant differences were observed when pattern AI
      was compared with pattern AII (P = 0.0280), AIII (P = 0.0024), BIII (P = 0.0077)
      and total B (P = 0.0247). In patients aged >37 years, statistical differences
      among groups were not observed. CONCLUSIONS: In patients aged </=37 years,
      zygotes with similar PN size and with polarized NPB present the best prognosis
      based on embryo development and the incidence of chromosomal abnormalities,
      whereas in patients aged >37 years, this correlation does not exist.

PMID- 14585896
TI  - Cryopreservation of follicles in human ovarian cortical tissue. Comparison of
      serum and human serum albumin in the cryoprotectant solutions.
AB  - BACKGROUND: Cryopreservation of follicles in ovarian cortical tissue has been
      suggested as a method for preserving fertility for young women who need to
      undergo cytotoxic therapy. Varying compositions of cryoprotectant solutions have
      been used to prevent tissue damage during cryopreservation and thawing. We
      compared human serum [20% (v/v)] and human serum albumin (HSA) (25 mg/ml) in
      cryoprotectant solutions containing propanediol and sucrose to evaluate whether
      serum-free medium could be used for this purpose. METHODS: Biopsies of ovarian
      cortical tissue were obtained from 23 subjects after informed consent. Fourteen
      underwent Caesarean section and nine underwent sterilization by laparoscopy. The
      cortical tissue was cut into pieces of 1-1.5 mm(3 )and cryopreserved in
      cryoprotectant solutions containing serum or HSA. After thawing, a total of 1318
      follicles were analysed using light microscopy, transmission electron microscopy
      (TEM) or live/dead assay. RESULTS: Viability of the follicles was 99.3% in
      freshly dissected tissue. After thawing, 65% of the follicles and 75% of the
      oocytes were viable with serum, and 69 and 74%, respectively, with HSA. No
      significant differences were observed between results in solutions containing
      serum versus HSA. TEM showed similar results; however, poor survival of stromal
      tissue was evident in this analysis. The live/dead assay showed 82% viability
      after thawing for both groups. No benefits were seen from post-thawing culture
      for 4 h before histological preparation. CONCLUSIONS: A cryoprotectant solution
      containing HSA was equally effective as one containing serum. Good viability of
      follicles was confirmed when using propanediol and sucrose as cryoprotectants,
      with a large number of follicles.

PMID- 14585898
TI  - Office hysteroscopy and compliance: mini-hysteroscopy versus traditional
      hysteroscopy in a randomized trial.
AB  - BACKGROUND: Diagnostic hysteroscopy has not yet been generally accepted as a well
      tolerated office procedure. The aim of our study was to verify compliance, side
      effects and haemodynamic variations when a mini-hysteroscope is used. METHODS: A
      prospective randomized trial on office hysteroscopy was performed by comparing
      the use of a traditional 5 mm hysteroscope (group A) and of a 3.3 mm mini
      hysteroscope (group B). Two patient groups (A and B), each comprising 100 cases,
      were formed on the basis of a randomized computer-generated list. RESULTS: A
      marked reduction in the mean (+/- SD) pelvic pain score during office
      hysteroscopy was seen in group B (2.3 +/- 2.1) as compared with group A (4.6 +/-
      2.2) (P < 0.0001, Mann-Whitney test). This result was also confirmed when using
      an alternative approach: four classes of pelvic pain at the visual analogue score
      (VAS). A significant reduction was observed in the incidence of moderate and
      severe pelvic pain in group B at the end of the examination (P = 0.001) and 5-10
      min later (P < 0.05). CONCLUSIONS: The use of mini-hysteroscopes (3.3 mm with
      diagnostic sheath) lowers considerably the level of pelvic pain the patients
      feel: it is halved in comparison with traditional calibre hysteroscopes (2.3 +/-
      2.1, on a 0-10 VAS). Furthermore the outpatient hysteroscopy failure rate is less
      than half (2%) with the mini-hysteroscope compared with the traditional 5 mm
      hysteroscope (5%). As for side-effects and haemodynamic parameters, no
      differences were observed except for an increase (P < 0.05) in bradycardia in
      group B. The advantage of this technique is self-evident, if the patients'
      compliance is taken into account: in many cases the introduction or withdrawal of
      the vaginal speculum was reported as the greatest discomfort.

PMID- 14585897
TI  - Inner mitochondrial membrane potential (DeltaPsim), cytoplasmic ATP content and
      free Ca2+ levels in metaphase II mouse oocytes.
AB  - BACKGROUND: The relative magnitude of the inner mitochondrial membrane potential
      (DeltaPsim) has been suggested to indicate the competence of mammalian gametes
      and early embryos. This study examined the response of cultured somatic cells and
      mouse oocytes to inhibitors and conditions that affect DeltaPsim or metabolism,
      or both, and measured treatment-specific changes in ATP and cytoplasmic free
      Ca(2+). METHODS: During and after treatment, relative DeltaPsim, free Ca(2+), and
      ATP levels and cortical granule density were determined. RESULTS: Comparable
      responses of somatic cells and metaphase II mouse oocytes to experimental
      manipulations that affect DeltaPsim and metabolism were observed and reversible
      loss of DeltaPsim was associated with increased intracellular free Ca(2+), which
      in certain instances resulted in parthenogenetic activation. CONCLUSION: The
      findings support a mitochondrial basis for pericortical J-aggregate fluorescence
      but not for a direct association between high DeltaPsim and metabolism. The
      results extend previous findings indicating that high-polarized (high DeltaPsim,
      JC-1 J-aggregate-forming) mitochondria occur in pericortical domains in mouse and
      human oocytes and early preimplantation stage embryos and support the notion that
      this spatial distribution may be related to localized ionic and metabolic
      regulation.

PMID- 14585899
TI  - Carbon dioxide versus normal saline in outpatient hysteroscopy.
AB  - BACKGROUND: The aim of this prospective randomized study was to measure patients'
      discomfort after hysteroscopy with CO(2) or normal saline. METHODS: A total of
      415 patients was randomized to two groups according to distension medium (CO(2),
      n = 201; normal saline, n = 214). The nature of randomization was to alternate
      distension media on a weekly basis. After hysteroscopy, women were asked to rate
      the pain experienced on a 100-mm visual analogue scale (0 = no pain; 100 = worst
      imaginable pain). Pain scores were expressed as mean +/- SD (0-40 = minimal; 41
      70 = moderate; 71-100 = severe). Data were analysed using Student's t-test.
      RESULTS: Irrespective of the distension medium used, pelvic discomfort was worse
      in nulliparous women (pain score 39.0 +/- 26.5) than in multiparous women (30.4
      +/- 25.9) (P < 0.05), especially if they were premenopausal. For all patients and
      both distension media, pelvic discomfort was generally minimal but higher in
      patients who had undergone hysteroscopy with normal saline (P < 0.05).
      CONCLUSIONS: CO(2) and normal saline were comparable with regard to patient
      discomfort, but in terms of the high frequency of abnormal uterine bleeding,
      normal saline may be the most appropriate distension medium for outpatient
      hysteroscopy.

PMID- 14585900
TI  - Does laparoscopic excision of endometriotic ovarian cysts significantly affect
      ovarian reserve? Insights from IVF cycles.
AB  - BACKGROUND: Residual ovarian function after laparoscopic excision of
      endometriotic ovarian cysts is a major and still unsolved topic. Ultrasonographic
      evaluation of ovarian response to ovulation stimulation represents a simple yet
      poorly employed tool to assess residual ovarian function after surgery. METHODS:
      Data from patients referred for IVF or ICSI between January 2001 and December
      2002 were reviewed. Patients were included who previously underwent laparoscopic
      excision of a monolateral endometriotic ovarian cyst. The operated ovary and
      contralateral intact ovary were compared in terms of number of follicles with a
      mean diameter >15 mm at the time of hCG administration. Basal volume of the two
      ovaries before initiating stimulation was also compared. A paired Student's t
      test was used to investigate differences between the two ovaries. RESULTS: In
      total, 32 patients and 46 cycles were identified. The mean (+/- SD) number of
      follicles >15 mm was 4.2 +/- 2.5 in the control ovary and 2.0 +/- 1.5 in the
      previously operated ovary (P < 0.001); this corresponded to a mean reduction of
      53% (95% CI 35-72%) but did not seem to be related to the dimension of the
      excised ovarian cyst. The basal volume of the operated ovaries was also
      statistically significantly diminished, though this reduction was less relevant.
      CONCLUSIONS: Excision of endometriotic ovarian cysts is associated with a
      significant reduction in ovarian reserve. Further studies are required to clarify
      whether the damage is related to the surgical procedure or to the previous
      presence of a cyst.

PMID- 14585901
TI  - Anatomic and functional results of laparoscopic-perineal neovagina construction
      by sigmoid colpoplasty in women with Rokitansky's syndrome.
AB  - BACKGROUND: The Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is a rare
      congenital cause of primary amenorrhea, due to utero-vaginal agenesis. Several
      surgical techniques have been used to create a neovagina. Neovagina construction
      with a sigmoid graft appears to be the best option, as it offers adequate length
      and natural lubrication, allowing early intercourse. However, few data are
      available on the complications, anatomic and functional results of laparoscopic
      perineal neovagina construction by sigmoid colpoplasty. METHODS: From September
      1995 to November 2002, seven women with the MRKH syndrome underwent laparoscopic
      perineal neovagina construction by sigmoid grafting. RESULTS: The mean operating
      time was 312 min (range 220-450 min). The mean fall in haemoglobin was 3.6 g/dl
      (range 2-4.4 g/dl). Blood transfusion was never necessary. The only perioperative
      complications were one urinary tract infection and one vulvar haematoma not
      requiring drainage. The mean hospital stay was 7.7 days (range 6-12 days). The
      mean length of the neovagina was 11.5 cm (range 7-15 cm), and no shrinkage
      occurred during follow-up. The neovaginal introitus admitted two fingers in
      breadth in five of the seven patients. Dilation of the introitus was required in
      the other two women. None of the four women who had intercourse experienced
      dyspareunia or discomfort. CONCLUSION: Our results confirm the feasibility of
      laparoscopic-perineal neovagina construction by sigmoid colpoplasty, when
      performed by surgeons with extensive experience in both gynaecological and
      gastrointestinal laparoscopic surgery. The anatomic and functional results were
      good.

PMID- 14585902
TI  - Dizygotic twinning is not associated with methylenetetrahydrofolate reductase
      haplotypes.
AB  - BACKGROUND: Folate metabolism is critical to embryonic development, influencing
      neural tube defects (NTD) and recurrent early pregnancy loss. Polymorphisms in
      5,10-methylenetetrahydrofolate reductase (MTHFR) have been associated with
      dizygotic (DZ) twinning through pregnancy loss. METHODS: The C677T and A1298C
      polymorphisms in MTHFR were genotyped in 258 Australasian families (1016
      individuals) and 118 Dutch families (462 individuals) of mothers of DZ twins and
      a population sample of 462 adolescent twin families (1861 individuals).
      Haplotypes were constructed from the alleles, and transmission of the MTHFR
      haplotypes to mothers of DZ twins and from parents to twins in the adolescent
      twin families analysed. RESULTS: The C677T and A1298C were common in all three
      populations (frequencies > 0.29). There was strong linkage disequilibrium (D' =
      1) between the variants, showing that specific combinations of alleles
      (haplotypes) were transmitted together. Three haplotypes accounted for nearly all
      the variation. There was no evidence of any association between MTHFR genotype
      and twinning in mothers of twins, or of the loss of specific MTHFR genotypes
      during twin pregnancies. CONCLUSIONS: It is concluded that variation in twinning
      frequency is not associated with MTHFR genotype.

PMID- 14585903
TI  - Prospective, serial investigations of in-vitro lymphocyte cytokine production,
      CD62L expression and proliferative response to microbial antigens in women with
      recurrent miscarriage.
AB  - BACKGROUND: Lymphocytes from pregnant women with unexplained recurrent
      miscarriage (RM) may be characterized by a T-helper type 1-dominated cytokine
      production and a higher proliferative response to microbial recall antigens
      compared with normal pregnant women. METHODS: Serial blood samples were taken
      from 14 women with RM (at least three previous consecutive miscarriages) during
      the first 14 weeks of pregnancy, and one blood sample was taken from 15 control
      women in gestational weeks 7-8. Of the 14 pregnant RM patients, four produced a
      live birth and 10 miscarried. Lymphocytes were in-vitro-stimulated by mitogens,
      allogeneic cells and microbial antigens, and the production of a series of
      cytokines, the proliferative responses and lymphocytic expression of CD62L (which
      may be a marker of T-helper type 2 lymphocytes) were measured. RESULTS: Repeated
      measurements of cytokine production were reproducible during the first trimester.
      The proliferative responses to herpes simplex and tetanus antigens were
      increased, and the ratio of CD62L-/CD62L+ expressing CD4+CD45RO+ lymphocytes was
      decreased in patients compared with controls (P = 0.01, P < 0.01 and P < 0.01
      respectively). CONCLUSION: The results of the in-vitro assays used were
      reproducible in serial testing during pregnancy. The importance of CD62L
      expression on lymphocytes for RM and the relevance of the maternal response to
      microbial antigens during pregnancy should be further explored.

PMID- 14585904
TI  - Polymorphisms in the ACE and PAI-1 genes are associated with recurrent
      spontaneous miscarriages.
AB  - BACKGROUND: Successful pregnancies require fine tuning of fibrinolytic activities
      in order to secure fibrin polymerization and stabilization of the placental basal
      plate as well as to prevent excess fibrin deposition in placental vessels and
      intervillous spaces. Fibrinolysis is tightly regulated by plasminogen activator
      inhibitor-1 (PAI-1). Endothelial PAI-1 synthesis is induced by angiotensin II,
      which is generated by angiotensin I-converting enzyme (ACE). METHODS: We studied
      the ACE deletion (D)/insertion (I) polymorphism and the PAI-1 4G/5G polymorphism
      in women with recurrent spontaneous miscarriages (RM). Both polymorphisms have
      been shown to be associated with ACE and PAI-1 expression levels respectively. A
      study group of 184 patients with a history of two or more consecutive unexplained
      spontaneous miscarriages was compared with a control group of 127 patients with
      uneventful term deliveries and no history of miscarriages. RESULTS: Our findings
      show: (i) homozygosity for the D allele of the ACE gene, which results in
      elevated PAI-1 concentrations and hypofibrinolysis, is associated with an
      elevated risk of RM; (ii) the combination of the D/D genotype with two 4G alleles
      of the PAI-1 promoter, which further increases PAI-1 plasma levels, is
      significantly more frequent in RM patients compared with controls. CONCLUSIONS:
      Based on these results, we recommend the incorporation of these two polymorphisms
      into the spectrum of thrombophilic mutations which should be analysed in
      individuals with recurrent spontaneous miscarriages. Patients homozygous for both
      the ACE D and PAI-1 4G alleles may benefit from the application of low molecular
      weight heparin as early as possible in the pregnancy in order to prevent
      uteroplacental microthromboses.

PMID- 14585905
TI  - Infertility and preterm delivery, birthweight, and Caesarean section: a study
      within the Danish National Birth Cohort.
AB  - BACKGROUND: More than 10% of babies are born to couples taking >1 year to
      conceive (a common definition of infertility). Some evidence indicates that such
      pregnancies are at increased risk of preterm delivery and other adverse birth
      outcomes, but the problem has rarely been addressed in large, longitudinal
      studies enrolling couples irrespective of infertility treatment. METHODS: We used
      data from the Danish National Birth Cohort: 55 906 singleton live births from
      women who reported their waiting time to pregnancy (TTP) and other covariates in
      an interview during the 2nd trimester of pregnancy. RESULTS: A TTP >1 year was
      associated with an increased risk of all outcomes studied, including preterm
      birth [odds ratios and 95% confidence intervals were 1.5 (1.2, 1.8) among
      primiparas and 1.9 (1.5, 2.4) among multiparas]. Odds ratios for preterm remained
      elevated after adjustment for covariates. Among couples with a TTP >1 year,
      infertility treatment was associated with added risk only among multiparas.
      CONCLUSION: Infertile women are at higher risk of adverse birth outcomes even if
      they conceive without treatment. With >10% of babies born to infertile couples,
      it is important to consider this group as potentially high risk when providing
      prenatal care.

PMID- 14585906
TI  - Pregnancy rate fluctuations during routine work in an assisted reproduction
      technology unit.
AB  - BACKGROUND: Fluctuations in spontaneous pregnancy rates have been observed in the
      general population. The purpose of this study was to evaluate whether pregnancy
      rates fluctuate over time in a homogeneous assisted reproduction treatment unit.
      METHODS: The study sample consisted of 3522 consecutive assisted reproduction
      cycles conducted from January 1996 to December 1999. Only fresh cycles in women
      <41 years old were included. All pertinent clinical data were prospectively
      collected on a computerized database and analysed at the end of the study.
      RESULTS: Throughout the 4 years of the study, monthly pregnancy rates fluctuated
      between 10.5 and 34.1% (mean 21.4%) per cycle, and between 13.6 and 41% (mean
      27.26%) per transfer. These fluctuations did not follow any specific seasonal
      pattern. CONCLUSION: During routine work in an assisted reproduction treatment
      unit, there are random fluctuations in the pregnancy rate. This factor should be
      considered in studies performed in a specific time-period.

PMID- 14585907
TI  - Present options for treating sperm autoimmunity before proteomic analysis is
      available.

PMID- 14585909
TI  - The male disadvantage and the seasonal rhythm of sex ratio at the time of
      conception.

PMID- 14585912
TI  - Channelling of patients taking NSAIDs or cyclooxygenase-2-specific inhibitors and
      its effect on interpretation of outcomes.
AB  - When new drugs with improved safety or efficacy are introduced, they may be
      preferentially prescribed to specific populations of patients. Safety and
      efficacy may be underestimated if such channelling effects are not recognized.
      Meloxicam and cyclooxygenase (COX)-2-specific inhibitors were developed as safer
      alternatives to non-steroidal anti-inflammatory drugs (NSAIDs) for the treatment
      of osteoarthritis and rheumatoid arthritis. Studies of the use of meloxicam and
      COX-2-specific inhibitors demonstrate that both of these drugs are being
      prescribed to patients at increased risk of gastrointestinal adverse drug events.
      In the case of COX-2-specific inhibitors, this channelling appears to represent a
      prescribing pattern consistent with current recommendations. Subsequent analysis
      of the data, after adjusting for channelling bias, showed that the risk of
      gastrointestinal toxicity for meloxicam was similar to that for other NSAIDs,
      while COX-2-specific inhibitors reduced the risk of developing gastrointestinal
      adverse drug events by approximately 60%. These studies serve as examples of
      observed channelling bias and highlight the need for adjusting for channelling in
      order to provide a valid assessment of relevant outcomes for drugs likely to be
      preferentially prescribed to specific populations.

PMID- 14585913
TI  - Drug utilization review of celecoxib in Ontario.
AB  - Cyclooxygenase (COX)-2-specific inhibitors were developed to circumvent the
      gastrointestinal toxicity of non-specific non-steroidal anti-inflammatory drugs
      while maintaining efficacy. However, the higher acquisition cost of COX-2
      specific inhibitors has resulted in the implementation of a programme for cost
      containment in the Ontario public drug program. This programme consists of
      limited use (LU) criteria that need to be met for drug reimbursement of patients
      with osteoarthritis (OA) or rheumatoid arthritis (RA). Determining the proportion
      of patients eligible for reimbursement for celecoxib according to the LU criteria
      (based on prior treatment failure and the presence or history of serious ulcer
      related gastrointestinal complications) can provide an indication of the extent
      of adherence to suggested guidelines. Using a patient-based survey and an
      analysis of the Ontario Drug Benefit Program database, the proportion of patients
      prescribed celecoxib who met rigorous or pragmatic definitions of the LU criteria
      was determined. The extent of coprescription of gastroprotective agents among
      patients taking celecoxib was also determined. Using the pragmatic definition,
      the majority of patients in the patient-based survey (53% for OA and 81% for RA)
      met the LU criteria. Similarly, in the database analysis, the majority of
      patients (76% for OA and 78% for RA) met the LU criteria. These data suggest that
      physician prescribing of celecoxib is consistent with the LU criteria.
      Concomitant prescription of gastroprotective agents in patients taking celecoxib
      was approximately 40%. It is recommended that further investigations be performed
      to determine the long-term impact of LU criteria on clinical and economic
      outcomes, since these criteria may also serve to restrict use in patients who may
      benefit from taking COX-2-specific inhibitors.

PMID- 14585914
TI  - Persistency of use of COX-2-specific inhibitors and non-specific non-steroidal
      anti-inflammatory drugs (NSAIDs) in Quebec.
AB  - The effectiveness of pharmacological therapies is dependent in part on patient
      persistency with the prescribed therapeutic regimen. In the case of non-specific
      non-steroidal anti-inflammatory drugs (NSAIDs), effectiveness is often
      compromised by undesirable side-effects, poor compliance or discontinuation of
      therapy. While patterns of utilization of non-specific NSAIDs have been
      investigated, few data are available on the patterns of persistency for
      cyclooxygenase (COX)-2-specific inhibitors. This study used a provincial health
      care system database in Quebec, Canada, to determine the duration of treatment in
      new users of COX-2-specific inhibitors and non-specific NSAIDs over the first 3
      months of treatment, and to characterize the factors associated with treatment
      persistency. Results demonstrate that the median duration of treatment was longer
      among patients initially prescribed COX-2-specific inhibitors (30 days and 23
      days for celecoxib and rofecoxib respectively) than in those prescribed non
      selective NSAIDs (10 days). Although the percentage of patients remaining on COX
      2-specific drugs declined over the course of treatment, few patients on either
      celecoxib or rofecoxib switched drugs, either to the other COX-2-specific
      inhibitor or to non-specific NSAIDs. Factors associated with persistent drug use
      were: COX-2-specific inhibitors, age, and the use of gastroprotective agents
      either at treatment initiation or during follow-up. Dosage, chronic disease score
      and prescriber's specialty were only marginally associated with persistency.
      Prior use of gastroprotective agents was associated with lower persistency.
      Although the limitations of this study, which included lack of information on the
      indication for the prescription and the reason for switch or discontinuation,
      preclude definite conclusions regarding patterns of use of these drugs, the data
      suggest that the use of COX-2-specific inhibitors may result in increased
      persistency with treatment.

PMID- 14585916
TI  - Measuring dyspepsia-related health in randomized trials: the Severity of
      Dyspepsia Assessment (SODA) and its use in treatment with NSAIDs and COX-2
      specific inhibitors.
AB  - Dyspepsia is a common problem that is important from the perspectives of both
      patient health and economics. While there has been variability in the definitions
      used to describe dyspepsia, there have also been few standardized outcomes tools
      designed to measure dyspepsia-related health, especially in relation to changes
      in dyspepsia over time. An evaluative tool was developed, the Severity of
      Dyspepsia Assessment (SODA), which takes into account the multidimensional nature
      of dyspepsia using three scales (Pain, Non-pain Symptoms, and Satisfaction with
      Dyspepsia-related Health) and demonstrates good psychometric properties with
      respect to validity, reliability and sensitivity to change in the measurement of
      dyspepsia-related health. Although originally developed for the assessment of
      uninvestigated dyspepsia, the validation of SODA for use in clinical trials
      suggested its ability to compare treatment effects of non-specific non-steroidal
      anti-inflammatory drugs (NSAIDs) and cyclooxygenase (COX)-2-specific inhibitors.
      In comparative trials of celecoxib or valdecoxib with non-specific NSAIDs, COX-2
      specific inhibitors were demonstrated to have superior dyspepsia tolerability
      than non-specific NSAIDs. These data demonstrate that SODA is an effective
      instrument for measuring dyspepsia-related health with a broad range of
      applications.

PMID- 14585915
TI  - Underutilization of preventive strategies in patients receiving NSAIDs.
AB  - BACKGROUND: Multiple treatment guidelines for non-steroidal anti-inflammatory
      drugs (NSAIDs) suggest that patients with one or more risk factors for NSAID
      associated upper gastrointestinal (UGI) ulcer complications should be prescribed
      preventive strategies such as acid-suppressive drugs, misoprostol or
      cyclooxygenase (COX)-2-specific inhibitors to reduce their risk of serious ulcer
      complications. The purpose of the present study was to evaluate the extent to
      which new NSAID users receive recommended preventive strategies and to assess the
      association between risk factors and a prescription of acid suppressive drugs or
      misoprostol. METHOD: A retrospective observational cohort study was conducted
      using the Integrated Primary Care Information (IPCI) database, a longitudinal
      database of electronic general practitioner patient records in The Netherlands.
      The study population comprised all new NSAID users, defined as users of non
      specific NSAIDs, COX-2-preferential NSAIDs and COX-2-specific inhibitors, during
      the period from January 1996 to April 2002. Subjects were excluded if they had an
      H2-receptor antagonist (H2RA), proton pump inhibitor (PPI) or misoprostol
      prescription in the 3 months prior to the first NSAID prescription. Preventive
      use of acid-suppressive drugs or misoprostol was identified by the coprescription
      for these drugs on the same day (+/-2 days) as the NSAID prescription. The drug
      use for each patient was validated as having a preventive indication by reviewing
      the physician-recorded symptoms and diagnoses. Risk factors for UGI ulcer events
      were defined as age >65 yr, UGI history (gastroduodenal ulcer, UGI bleeding,
      dyspepsia) and concomitant medications (anticoagulants, aspirin, oral
      corticosteroids). The study population comprised 69 648 new NSAID users. RESULTS:
      Overall, 7.9% of NSAID users received a preventive strategy (6.6% received a
      gastroprotective agent and an additional 1.3% received COX-2-specific
      inhibitors). Patients using preventive drugs had higher odds of having one or
      more UGI risk factors than patients without preventive drugs [adjusted odds ratio
      (OR) 1.78, 95% confidence interval 1.66-1.92]. Despite the greater rate of
      preventive drug prescriptions in patients who may have been at higher risk, 86.6%
      of patients with one risk factor and 81.2% with two or more risk factors received
      no preventive strategies. In contrast to non-specific NSAIDs, patients who
      received a prescription for a COX-2-specific inhibitor had significantly lower
      adjusted odds (OR = 0.22) of having H2RA/PPI or misoprostol coprescribed.
      CONCLUSIONS: Although patients who are treated with preventive strategies have
      higher odds of having gastrointestinal risk factors than those not prescribed
      preventive therapies, the majority (>80%) of patients with one or more
      gastrointestinal risk factors do not receive the recommended NSAID treatment
      regimen of a COX-2-specific inhibitor or NSAID + H2RA/PPI or misoprostol and are
      therefore undertreated.

PMID- 14585917
TI  - The burden of acute postoperative pain and the potential role of the COX-2
      specific inhibitors.
AB  - Pain has been recognized as a problem of global proportions, and postoperative
      pain is one of the most common types of pain. Postoperative pain is acute and,
      although it is preventable and/or treatable, it is often undertreated. Lack of
      appropriate analgesic management has significant impact on clinical and economic
      outcomes. Negative clinical outcomes of inadequately managed acute postoperative
      pain include extended hospitalization, compromised prognosis, higher morbidity
      and mortality, and the development of a chronic pain state as a result of
      neuronal plasticity. Although estimating the economic burden of postoperative
      pain is difficult, this burden is considerable and results from direct costs due
      to excess health-care resource use, as well as indirect costs due to reduced
      patient functionality and productivity. These latter factors also have a
      significant adverse impact on patients' quality of life and may be associated
      with the development of depression and anxiety. Thus, improved clinical outcomes
      are dependent not only on the availability of effective drugs but also on their
      appropriate utilization. A multimodal approach incorporating different drugs and
      techniques is effective in reducing postoperative pain but is limited by the
      currently available therapies. The efficacy of opioids is well established, but
      there are concerns about dependency, respiratory depression and side-effects,
      which patients often find intolerable. Non-steroidal anti-inflammatory drugs
      (NSAIDs) are effective as adjunctive medication in a multimodal regimen but are
      associated with side-effects, such as platelet dysfunction and renal and
      gastrointestinal toxicity, that have special clinical significance in patients
      undergoing surgical procedures. Cyclooxygenase-2-specific inhibitors such as
      celecoxib, rofecoxib and valdecoxib, were developed to provide the efficacy of
      non-specific NSAIDs while limiting associated toxicity. These agents have
      demonstrated analgesic efficacy and an opioid-sparing effect in a variety of
      surgical procedures, suggesting their value as an alternative to non-specific
      NSAIDs. Further studies are needed to determine the impact of these drugs on
      clinical and economic outcomes when used in a programme of postsurgical pain
      management.

PMID- 14585918
TI  - Economic evaluation of oral valdecoxib versus diclofenac in the treatment of
      patients with rheumatoid arthritis in a randomized clinical trial.
AB  - In contrast to economic models that provide probabilistic estimates of economic
      impact, data extracted from clinical trials may be used to evaluate and compare
      actual resource utilization and costs. Health-care resource utilization and the
      costs of these resources were compared from the perspective of the UK National
      Health Service using data obtained in a 6-month clinical trial of oral valdecoxib
      20 mg once daily and diclofenac 75 mg twice daily for the symptomatic treatment
      of rheumatoid arthritis. However, calculated health-care costs were exclusive of
      drug acquisition costs because the price of valdecoxib was not available at the
      time of analysis. While the efficacy of the two treatments was similar, use of
      valdecoxib was associated with a reduction in total health-care costs amounting
      to approximately 200 British pounds per patient. This lower cost was associated
      with reduced use of health-care resources for gastrointestinal serious adverse
      events (gastrointestinal SAEs). In particular, the incidence of hospitalization
      and number of hospital days for gastrointestinal SAEs was lower in the valdecoxib
      group. Analysis of cost per gastrointestinal SAE favoured valdecoxib (cost
      savings of 742 British pounds), suggesting that even when these events did occur
      they were less severe. When costs of gastrointestinal SAEs were averaged over the
      entire population, valdecoxib was suggested to have lower total costs per patient
      compared with diclofenac (cost savings of 115 British pounds per patient), mainly
      resulting from significant savings in hospitalization costs (76.49 British pounds
      per patient). These data are consistent with economic models and suggest that the
      favourable gastrointestinal profile of valdecoxib observed in clinical trials
      will be of economic benefit.

PMID- 14585919
TI  - The use of health economic information by reimbursement authorities.
AB  - The increasing costs of health-care and the need for cost containment have
      resulted in a 'fourth hurdle' in the establishment of drug approval and
      reimbursement policies. This hurdle is the demonstration of a drug's cost
      effectiveness through the process of economic evaluation. The role of models in
      the economic evaluation of pharmaceuticals is becoming increasingly accepted with
      the recent trend towards developing models with greater transparency and clinical
      relevance. However, health-care decisions do not, and should not, rely solely on
      the cost-effectiveness of a drug or intervention. Factors such as disease
      severity, availability of alternative treatment strategies, cost of drugs to
      patients, compliance with therapy and patients' satisfaction with overall
      treatment effectiveness should also be considered, and in some cases can be
      incorporated into economic evaluation. The Arthritis Cost Consequences Evaluation
      System (ACCES) is provided as an example of the attributes and limitations that
      should be considered in determining the usefulness of a model for economic
      evaluations with the purpose of determining reimbursement policy decisions.

PMID- 14585921
TI  - Evaluation of capture ELISA for detection of antineutrophil cytoplasmic
      antibodies directed against proteinase 3 in Wegener's granulomatosis: first
      results from a multicentre study.
AB  - OBJECTIVE: To evaluate the performance characteristics of direct and capture
      ELISA for the detection of PR3-ANCA in Wegener's granulomatosis (WG) in
      international ANCA reference laboratories. METHODS: Serum samples were derived
      from patients with histological and clinical diagnosis of WG (n = 60), rheumatoid
      arthritis (RA) (n = 30) and healthy controls (n = 30). Each of them was tested
      for the presence of ANCA by indirect immunofluorescence technique (IFT), direct
      and capture ELISA in six international reference laboratories (Massachusetts
      General Hospital, Boston; Wieslab AB, Lund; University of Maastricht; University
      Hospital Groningen; Mayo Clinic, Rochester; Rheumaklinik Bad Bramstedt/University
      of Schleswig-Holstein Campus Lubeck). Each centre tested the sera according to
      their house protocols of IFT and ELISA. The diagnostic performance of each test
      was estimated by receiver operating characteristic curve analysis and sensitivity
      and specificity in detection of ANCA/PR3-ANCA were calculated for the respective
      methods. RESULTS: In patients histologically and clinically known as WG, the
      detection of ANCA by IFT varied between 52 and 83% among the participating
      centres. PR3-ANCA positivity with the different ELISAs ranged from 53 to 80% in
      direct ELISA and from 72 to 76% in capture ELISA. While most capture ELISAs
      successfully detected PR3-ANCA, there were significant differences between IFT
      and direct ELISA results between laboratories. ROC curve analysis demonstrated
      that in five of six laboratories the overall diagnostic performance of capture
      ELISA was superior to IFT and direct ELISA, respectively. CONCLUSION: Capture
      ELISA is a highly sensitive assay for detection of PR3-ANCA in WG and should be
      used in conjunction with compatible clinical picture and histological evidence.

PMID- 14585922
TI  - Comparison of different kits in the detection of autoantibodies to cardiolipin
      and beta2glycoprotein 1.
AB  - OBJECTIVE: To estimate the performance characteristics of 10 commercial kits and
      one in-house kit for the detection and quantification of anticardiolipin (aCL)
      (six kits) and anti-beta2glycoprotein 1 (anti-beta2GP1) (five kits) antibodies,
      and to evaluate the degree of variability between these different kits. METHODS:
      We determined the presence of aCL and anti-beta2GP1 IgG and IgM antibodies in 67
      sera from 62 patients and reviewed the data separately. Each serum sample was
      tested with six commercial aCL determination kits and with four commercial and
      one in-house anti-beta2GP1 determination kit. We then analysed the operating
      characteristics of each kit (sensitivity, specificity, positive and negative
      predictive values) and we analysed the absolute and 2 x 2 agreements. RESULTS:
      The 62 patients included had primary antiphospholipid syndrome (APS) in 10 cases,
      secondary APS for eight, systemic lupus (SLE) for 23 and other diagnoses for the
      remaining 21. Operating characteristics differed from one kit to another. Good
      agreement was found using sensitive aCL determination kit and specific anti
      beta2GP1 determination kit. Agreement between kits was medium for IgG aCL. 2 x 2
      concordance studies showed a group of three aCL kits which were quite homogenous
      and showed that all anti-beta2GP1 kits formed quite a homogenous group.
      CONCLUSION: A high degree of variability still persists for aCL antibody
      determination posing the question of the qualification of commercial or in-house
      kits and the question of standardization of results. A better concordance is
      found for high positive results. Good agreement exists for anti-beta2GP1 kits.
      aCL determination is still needed and should be complemented by anti-beta2GP1
      determination.

PMID- 14585923
TI  - Student-selected components in rheumatology--what, why, where and how?

PMID- 14585924
TI  - Can ultrasound predict histological findings in regenerated cartilage?
AB  - OBJECTIVE: To evaluate regenerated articular cartilage quantitatively by
      introducing an ultrasonic probe into the knee joint under arthroscopy and
      analysing the A-mode echogram by means of wavelet transformation. METHODS: Three
      experimental rabbit models (spontaneous repair model, large cartilage defect
      model, treatment model) were examined using our ultrasonic evaluation system and
      a histological grading scale. From resulting wavelet map, the percentage of
      maximum magnitude was selected as the quantitative index of the ultrasonic
      evaluation system. RESULTS: The percentage maximum magnitude in the spontaneous
      repair model was 61.1%, that in the large defect model was 29.8% and that in the
      treatment model was 36.3%. There was modest correlation between the percentage
      maximum magnitude and the histological grading scale (r = -0.594) CONCLUSION: Our
      findings indicate that ultrasound analysis can predict the microstructure of
      regenerated cartilage.

PMID- 14585925
TI  - Patients' preferences for characteristics associated with treatments for
      osteoarthritis.
AB  - OBJECTIVE: The purpose of this study was to investigate patient preferences for
      attributes associated with the efficacy and side-effects of treatment for
      osteoarthritis. METHODS: A stated preference design questionnaire was
      administered to a sample of 412 individuals diagnosed with osteoarthritis (OA).
      RESULTS: Statistically significant attributes in influencing treatment
      preferences were the level of joint aches, the level of physical mobility and the
      risk of experiencing serious side-effects from treatment. Respondents were
      relatively more concerned about the risk of serious side-effects (even with a
      very low probability) than mild to moderate side-effects (at a much higher
      probability). Data segmentation revealed some variations in preferences according
      to respondent characteristics. The importance of joint aches increased according
      to the severity of the symptoms of osteoarthritis, indicating that this attribute
      is more troublesome to those respondents with more severe symptoms. Older
      respondents were more willing than younger respondents to accept an increased
      risk of experiencing serious side-effects for an improvement in the symptoms of
      OA. Individuals in lower income brackets appeared to attach greater importance to
      joint aches and the level of mobility experienced than those in higher income
      brackets. Respondents who had previously experienced gastrointestinal side
      effects from treatment were, as expected, more tolerant of them than those who
      had not. CONCLUSION: The use of conjoint analysis to assess patient preferences
      provides a useful insight to the likely attitudes of patients to novel treatments
      for osteoarthritis.

PMID- 14585926
TI  - The crystal structures of severe acute respiratory syndrome virus main protease
      and its complex with an inhibitor.
AB  - A newly identified severe acute respiratory syndrome coronavirus (SARS-CoV), is
      the etiological agent responsible for the outbreak of SARS. The SARS-CoV main
      protease, which is a 33.8-kDa protease (also called the 3C-like protease), plays
      a pivotal role in mediating viral replication and transcription functions through
      extensive proteolytic processing of two replicase polyproteins, pp1a (486 kDa)
      and pp1ab (790 kDa). Here, we report the crystal structures of the SARS-CoV main
      protease at different pH values and in complex with a specific inhibitor. The
      protease structure has a fold that can be described as an augmented serine
      protease, but with a Cys-His at the active site. This series of crystal
      structures, which is the first, to our knowledge, of any protein from the SARS
      virus, reveal substantial pH-dependent conformational changes, and an unexpected
      mode of inhibitor binding, providing a structural basis for rational drug design.

PMID- 14585927
TI  - Identification and characterization of a cyclooxygenase-like enzyme from
      Entamoeba histolytica.
AB  - The intestinal protozoan parasite Entamoeba histolytica remains a significant
      cause of morbidity and mortality worldwide. However, almost nothing is known
      about the molecules secreted by the parasite that modulate host immune responses
      or epithelial barrier function in the colon. Herein, we describe the isolation
      and characterization of a cyclooxygenase (COX)-like enzyme in E. histolytica that
      is responsible for the biosynthesis of prostaglandin (PG)E2. PGE2 produced by
      ameba was constitutive but highly dependent on exogenous arachidonic acid
      substrate. COX-like activity and the immunoreactive protein were localized to the
      nuclear fraction of E. histolytica. The COX-like protein (72 kDa) was
      microsequenced and cloned by reverse transcriptase PCR. Ameba COX showed little
      homology with COX-1/2 enzymes from different species at the nucleotide and amino
      acid levels. Surprisingly, the arachidonate-binding domain and heme-coordinating
      and catalytic sites, which are conserved in other species, were absent in ameba.
      Ameba COX expressed in Escherichia coli demonstrated COX-like enzyme activity in
      vitro by converting arachidonic acid into PGE2 but not into PGD2 or PGF2alpha.
      COX activity was inhibited with 1 mM aspirin but not with indomethacin or COX-1/2
      specific inhibitors. Taken together, these studies reveal that E. histolytica
      produces PGE2, by means of a previously undescribed ancestral COX-like enzyme,
      which could play a major role in pathogenesis and immune evasion.

PMID- 14585928
TI  - ADP-ribosylation factor 6 regulates insulin secretion through plasma membrane
      phosphatidylinositol 4,5-bisphosphate.
AB  - ADP-ribosylation factor 6 (ARF6) is a small GTP-binding protein that regulates
      peripheral vesicular trafficking and actin cytoskeletal dynamics, and it has been
      implicated as critical to regulated secretion. Expression of a dominant
      inhibitory ARF6 mutant, ARF6(T27N), impaired glucose-, depolarization-, and gamma
      thio-GTP-stimulated insulin secretion in the pancreatic beta cell line, MIN6. In
      response to depolarization, MIN6 cells expressing ARF6(T27N) displayed an
      unaltered initial fast phase but an impaired subsequent slow phase of insulin
      secretion. Actin cytoskeletal disassembly with latrunculin A enhanced insulin
      secretion, whereas stabilization with jasplakinolide inhibited secretion,
      consistent with the actin cytoskeleton serving as a barrier to exocytosis in
      these cells. ARF6(T27N) led to a depolarization-dependent reduction in the levels
      of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] with a time course that
      paralleled the inhibition of secretion. Moreover, blockade of PI(4,5)P2-dependent
      events by expression of a lipid-binding protein resulted in inhibition of
      depolarization-induced secretion in a manner identical to ARF6(T27N). These
      results indicate that ARF6 is required to sustain adequate levels of PI(4,5)P2
      during periods of increased PI(4,5)P2 metabolism such as regulated secretion.

PMID- 14585929
TI  - The low gonadotropin-independent constitutive production of testicular
      testosterone is sufficient to maintain spermatogenesis.
AB  - Spermatogenesis is thought to critically depend on the high intratesticular
      testosterone (T) levels induced by gonadotropic hormones. Strategies for hormonal
      male contraception are based on disruption of this regulatory mechanism through
      blockage of gonadotropin secretion. Although exogenous T or T plus progestin
      treatments efficiently block gonadotropin secretion and suppress testicular T
      production, only approximately 60% of treated Caucasian men reach contraceptive
      azoospermia. We now report that in luteinizing hormone receptor knockout mice,
      qualitatively full spermatogenesis, up to elongated spermatids of late stages 13
      16, is achieved at the age of 12 months, despite absent luteinizing hormone
      action and very low intratesticular T (2% of control level). However, postmeiotic
      spermiogenesis was blocked by the antiandrogen flutamide, indicating a crucial
      role of the residual low testicular T level in this process. The persistent
      follicle-stimulating hormone action in luteinizing hormone receptor knockout mice
      apparently stimulates spermatogenesis up to postmeiotic round spermatids, as
      observed in gonadotropin-deficient rodent models on follicle-stimulating hormone
      supplementation. The finding that spermatogenesis is possible without a
      luteinizing hormone-stimulated high level of intratesticular T contradicts the
      current dogma. Extrapolated to humans, it may indicate that only total abolition
      of testicular androgen action will result in consistent azoospermia, which is
      necessary for effective male contraception.

PMID- 14585930
TI  - A role for Arf1 in mitotic Golgi disassembly, chromosome segregation, and
      cytokinesis.
AB  - In mitosis, chromosome, cytoskeleton, and organelle dynamics must be coordinated
      for successful cell division. Here, we present evidence for a role for Arf1, a
      small GTPase associated with the Golgi apparatus, in the orchestration of mitotic
      Golgi breakdown, chromosome segregation, and cytokinesis. We show that early in
      mitosis Arf1 becomes inactive and dissociates from Golgi membranes. This is
      followed by the dispersal of numerous Arf1-dependent peripheral Golgi proteins
      and subsequent Golgi disassembly. If Arf1 is kept in an active state by treatment
      with the small molecule H89 or expression of its GTP-locked form, intact Golgi
      membranes with bound peripheral proteins persist throughout mitosis. These cells
      enter mitosis but exhibit gross defects in chromosome segregation and cytokinetic
      furrow ingression. These findings suggest that mitotic Golgi disassembly depends
      on Arf1 inactivation and is used by the cell to disperse numerous peripheral
      Golgi proteins for coordinating the behavior of Golgi membranes, chromosomes, and
      cytoskeleton during mitosis.

PMID- 14585931
TI  - A specific endoribonuclease, RNase P, affects gene expression of polycistronic
      operon mRNAs.
AB  - The rnpA mutation, A49, in Escherichia coli reduces the level of RNase P at 43
      degrees C because of a temperature-sensitive mutation in C5 protein, the protein
      subunit of the enzyme. Microarray analysis reveals the expression of several
      noncoding intergenic regions that are increased at 43 degrees C compared with 30
      degrees C. These regions are substrates for RNase P, and they are cleaved less
      efficiently than, for example, tRNA precursors. An analysis of the tna, secG,
      rbs, and his operons, all of which contain RNase P cleavage sites, indicates that
      RNase P affects gene expression for regions downstream of its cleavage sites.

PMID- 14585932
TI  - A comparative study of motor-protein motions by using a simple elastic-network
      model.
AB  - In this work, we report on a study of the structure-function relationships for
      three families of motor proteins, including kinesins, myosins, and F1-ATPases, by
      using a version of the simple elastic-network model of large-scale protein
      motions originally proposed by Tirion [Tirion, M. (1996) Phys. Rev. Lett. 77,
      1905-1908]. We find a surprising dichotomy between kinesins and the other motor
      proteins (myosins and F1-ATPase). For the latter, there exist one or two dominant
      lowest-frequency modes (one for myosin, two for F1-ATPase) obtained from normal
      mode analysis of the elastic-network model, which overlap remarkably well with
      the measured conformational changes derived from pairs of solved crystal
      structures in different states. Furthermore, we find that the computed global
      conformational changes induced by the measured deformation of the nucleotide
      binding pocket also overlap well with the measured conformational changes, which
      is consistent with the "nucleotide-binding-induced power-stroke" scenario. In
      contrast, for kinesins, this simplicity breaks down. Multiple modes are needed to
      generate the measured conformational changes, and the computed displacements
      induced by deforming the nucleotide-binding pocket also overlap poorly with the
      measured conformational changes, and are insufficient to explain the large-scale
      motion of the relay helix and the linker region. This finding may suggest the
      presence of two different mechanisms for myosins and kinesins, despite their
      strong evolutionary ties and structural similarities.

PMID- 14585933
TI  - Locking the DNA topoisomerase I protein clamp inhibits DNA rotation and induces
      cell lethality.
AB  - Eukaryotic DNA topoisomerase I (Top1) is a monomeric protein clamp that functions
      in DNA replication, transcription, and recombination. Opposable "lip" domains
      form a salt bridge to complete Top1 protein clamping of duplex DNA. Changes in
      DNA topology are catalyzed by the formation of a transient phosphotyrosyl linkage
      between the active-site Tyr-723 and a single DNA strand. Substantial protein
      domain movements are required for DNA binding, whereas the tight packing of DNA
      within the covalent Top1-DNA complex necessitates some DNA distortion to allow
      rotation. To investigate the effects of Top1-clamp closure on enzyme catalysis,
      molecular modeling was used to design a disulfide bond between residues Gly-365
      and Ser-534, to crosslink protein loops more proximal to the active-site tyrosine
      than the protein loops held by the Lys-369-Glu-497 salt bridge. In reducing
      environments, Top1-Clamp was catalytically active. However, contrary to
      crosslinking the salt-bridge loops [Carey, J. F., Schultz, S. J., Sission, L.,
      Fazzio, T. G. & Champoux, J. J. (2003) Proc. Natl. Acad. Sci. USA 100, 5640
      5645], crosslinking the active-site proximal loops inhibited DNA rotation.
      Apparently, subtle alterations in Top1 clamp flexibility impact enzyme catalysis
      in vitro. Yet, the catalytically active Top1-Clamp was cytotoxic, even in the
      reducing environment of yeast cells. Remarkably, a shift in redox potential in
      glr1Delta cells converted the catalytically inactive Top1Y723F mutant clamp into
      a cellular toxin, which failed to induce an S-phase terminal phenotype. This
      cytotoxic mechanism is distinct from that of camptothecin chemotherapeutics,
      which stabilize covalent Top1-DNA complexes, and it suggests that the development
      of novel therapeutics that promote Top1-clamp closure is possible.

PMID- 14585935
TI  - HRPT2, a marker of parathyroid cancer.

PMID- 14585934
TI  - Escherichia coli nucleoside diphosphate kinase is a uracil-processing DNA repair
      nuclease.
AB  - Escherichia coli nucleoside diphosphate kinase (eNDK) is an XTP:XDP
      phosphotransferase that plays an important role in the regulation of cellular
      nucleoside triphosphate concentrations. It is also one of several recently
      discovered DNases belonging to the NM23/NDK family. E. coli cells disrupted in
      the ndk gene display a spontaneous mutator phenotype, which has been attributed
      to the mutagenic effects of imbalanced nucleotide pools and errors made by
      replicative DNA polymerases. Another explanation for the increased mutation rates
      is that endk- cells lack the nuclease activity of the NDK protein that is
      essential for a DNA repair pathway. Here, we show that purified, cloned endk is a
      DNA repair nuclease whose substrate is uracil misincorporated into DNA. We have
      identified three new catalytic activities in eNDK that act sequentially to repair
      the uracil lesion: (i) uracil-DNA glycosylase that excises uracil from single
      stranded and from U/A and U/G mispairs in double-stranded DNA; (ii) apyrimidinic
      endonuclease that cleaves double-stranded DNA as a lyase by forming a covalent
      enzyme-DNA intermediate complex with the apyrimidinic site created by the
      glycosylase; and (iii) DNA repair phosphodiesterase that removes 3'-blocking
      residues from the ends of duplex DNA. All three of these activities, as well as
      the nucleoside-diphosphate kinase, reside in the same protein. Based on these
      findings, we propose an editing function for eNDK as a mechanism by which the
      enzyme prevents mutations in DNA.

PMID- 14585936
TI  - Tools of the trade.

PMID- 14585937
TI  - Subcutaneous fondaparinux versus intravenous unfractionated heparin in the
      initial treatment of pulmonary embolism.
AB  - BACKGROUND: The standard initial treatment of hemodynamically stable patients
      with pulmonary embolism is intravenous unfractionated heparin, requiring
      laboratory monitoring and hospitalization. METHODS: We conducted a randomized,
      open-label trial involving 2213 patients with acute symptomatic pulmonary
      embolism to compare the efficacy and safety of the synthetic antithrombotic agent
      fondaparinux with those of unfractionated heparin and to document noninferiority
      in terms of efficacy. Patients received either fondaparinux (5.0, 7.5, or 10.0 mg
      in patients weighing less than 50, 50 to 100, or more than 100 kg, respectively)
      subcutaneously once daily or a continuous intravenous infusion of unfractionated
      heparin (ratio of the activated partial-thromboplastin time to a control value,
      1.5 to 2.5), both given for at least five days and until the use of vitamin K
      antagonists resulted in an international normalized ratio above 2.0. The primary
      efficacy outcome was the three-month incidence of the composite end point of
      symptomatic, recurrent pulmonary embolism (nonfatal or fatal) and new or
      recurrent deep-vein thrombosis. RESULTS: Forty-two of the 1103 patients randomly
      assigned to receive fondaparinux (3.8 percent) had recurrent thromboembolic
      events, as compared with 56 of the 1110 patients randomly assigned to receive
      unfractionated heparin (5.0 percent), for an absolute difference of -1.2 percent
      in favor of fondaparinux (95 percent confidence interval, -3.0 to 0.5). Major
      bleeding occurred in 1.3 percent of the patients treated with fondaparinux and
      1.1 percent of those treated with unfractionated heparin. Mortality rates at
      three months were similar in the two groups. Of the patients in the fondaparinux
      group, 14.5 percent received the drug in part on an outpatient basis.
      CONCLUSIONS: Once-daily, subcutaneous administration of fondaparinux without
      monitoring is at least as effective and is as safe as adjusted-dose, intravenous
      administration of unfractionated heparin in the initial treatment of
      hemodynamically stable patients with pulmonary embolism.

PMID- 14585938
TI  - Comparison of ximelagatran with warfarin for the prevention of venous
      thromboembolism after total knee replacement.
AB  - BACKGROUND: In a previous study of the prevention of venous thromboembolism after
      total knee replacement, the efficacy of ximelagatran, an oral direct thrombin
      inhibitor that does not require monitoring of coagulation or dose adjustment, was
      found to be similar to that of warfarin at a dose of 24 mg of ximelagatran twice
      daily. The purpose of the present study was to determine whether a higher dose of
      ximelagatran is superior to warfarin. METHODS: This randomized, double-blind
      trial compared a regimen of 7 to 12 days of oral ximelagatran, at a dose of 24 or
      36 mg twice daily, starting the morning after surgery, with warfarin therapy
      started the evening of the day of surgery. The composite end point of venous
      thromboembolism and death from all causes and the incidence of bleeding were the
      primary outcome measures. RESULTS: Among the 1851 patients in the efficacy
      analysis, oral ximelagatran at a dose of 36 mg twice daily was superior to
      warfarin with respect to the primary composite end point of venous
      thromboembolism and death from all causes (20.3 percent vs. 27.6 percent;
      P=0.003). There were no significant differences between these two groups with
      respect to major bleeding (incidence, 0.8 percent and 0.7 percent, respectively),
      perioperative indicators of bleeding, wound characteristics, or the composite
      secondary end point of proximal deep-vein thrombosis, pulmonary embolism, and
      death (2.7 percent vs. 4.1 percent; P=0.17). CONCLUSIONS: The efficacy of oral
      ximelagatran, administered starting the morning after total knee replacement, was
      superior to that of warfarin for prevention of venous thromboembolism. Rates of
      hemorrhagic complications with the two drugs were similar.

PMID- 14585940
TI  - Somatic and germ-line mutations of the HRPT2 gene in sporadic parathyroid
      carcinoma.
AB  - BACKGROUND: We looked for mutations of the HRPT2 gene, which encodes the
      parafibromin protein, in sporadic parathyroid carcinoma because germ-line
      inactivating HRPT2 mutations have been found in a type of familial
      hyperparathyroidism--hyperparathyroidism-jaw tumor (HPT-JT) syndrome--that
      carries an increased risk of parathyroid cancer. METHODS: We directly sequenced
      the full coding and flanking splice-junctional regions of the HRPT2 gene in 21
      parathyroid carcinomas from 15 patients who had no known family history of
      primary hyperparathyroidism or the HPT-JT syndrome at presentation. We also
      sought to confirm the somatic nature of the identified mutations and tested the
      carcinomas for tumor-specific loss of heterozygosity at HRPT2. RESULTS:
      Parathyroid carcinomas from 10 of the 15 patients had HRPT2 mutations, all of
      which were predicted to inactivate the encoded parafibromin protein. Two distinct
      HRPT2 mutations were found in tumors from five patients, and biallelic
      inactivation as a result of a mutation and loss of heterozygosity was found in
      one tumor. At least one HRPT2 mutation was demonstrably somatic in carcinomas
      from six patients. Unexpectedly, HRPT2 mutations in the parathyroid carcinomas of
      three patients were identified as germ-line mutations. CONCLUSIONS: Sporadic
      parathyroid carcinomas frequently have HRPT2 mutations that are likely to be of
      pathogenetic importance. Certain patients with apparently sporadic parathyroid
      carcinoma carry germ-line mutations in HRPT2 and may have the HPT-JT syndrome or
      a phenotypic variant.

PMID- 14585939
TI  - Secondary prevention of venous thromboembolism with the oral direct thrombin
      inhibitor ximelagatran.
AB  - BACKGROUND: For many patients with venous thromboembolism, secondary prevention
      with vitamin K antagonists is not extended beyond six months, since the risk of
      recurrence may be outweighed by the risk of major bleeding. METHODS: In a double
      blind, multicenter trial, we randomly assigned 1233 patients with venous
      thromboembolism who had undergone six months of anticoagulant therapy to extended
      secondary prevention with the oral direct thrombin inhibitor ximelagatran (24 mg)
      or placebo, taken twice daily, for 18 months without monitoring of coagulation.
      At base line, bilateral ultrasonography of the legs and perfusion lung scanning
      were performed. RESULTS: Data from 612 patients in the ximelagatran group and 611
      in the placebo group were analyzed. The occurrence of the primary end point,
      symptomatic recurrent venous thromboembolism, was confirmed in 12 patients
      assigned to ximelagatran and 71 patients assigned to placebo (hazard ratio, 0.16;
      95 percent confidence interval, 0.09 to 0.30; P<0.001). Death from any cause
      occurred in 6 patients in the ximelagatran group and 7 patients in the placebo
      group, and bleeding occurred in 134 patients and 111 patients, respectively
      (hazard ratio, 1.19; 95 percent confidence interval, 0.93 to 1.53; P=0.17). The
      incidence of major hemorrhage was low (six events in the ximelagatran group and
      five in the placebo group), and none of these hemorrhages were fatal. The
      cumulative risk of a transient elevation of the alanine aminotransferase level to
      more than three times the upper limit of normal was 6.4 percent in the
      ximelagatran group, as compared with 1.2 percent in the placebo group (P<0.001).
      CONCLUSIONS: Oral ximelagatran was superior to placebo for the extended
      prevention of venous thromboembolism. There was no significant increase in the
      frequency of bleeding complications, but there was an increase in the number of
      patients with a transient elevation in the alanine aminotransferase level.

PMID- 14585941
TI  - Images in clinical medicine. Cerebral venous thrombosis.

PMID- 14585942
TI  - The toxicology of mercury--current exposures and clinical manifestations.

PMID- 14585943
TI  - Schizophrenia.

PMID- 14585944
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 34-2003. A 45-year-old woman with a family history of colonic
      polyps and cancer.

PMID- 14585945
TI  - Treating thrombosis in the 21st century.

PMID- 14585946
TI  - Can we prevent cerebral palsy?

PMID- 14585947
TI  - Enfuvirtide, an HIV-1 fusion inhibitor.

PMID- 14585948
TI  - Bacterial meningitis in children with cochlear implants.

PMID- 14585949
TI  - Aortic stenosis, von Willebrand factor, and bleeding.

PMID- 14585950
TI  - Microsatellite instability in colon cancer.

PMID- 14585951
TI  - Patients who refuse food and fluids to hasten death.

PMID- 14585952
TI  - Long-term outcomes after successful early defibrillation.

PMID- 14585953
TI  - Hogwarts headaches--misery for muggles.

PMID- 14585954
TI  - Images in clinical medicine. Bony ghosts--residual effects of severe growth
      arrest.

PMID- 14585955
TI  - Replication-independent assembly of nucleosome arrays in a novel yeast chromatin
      reconstitution system involves antisilencing factor Asf1p and chromodomain
      protein Chd1p.
AB  - Chromatin assembly in a crude DEAE (CD) fraction from budding yeast is ATP
      dependent and generates arrays of physiologically spaced nucleosomes which
      significantly protect constituent DNA from restriction endonuclease digestion.
      The CD fractions from mutants harboring deletions of the genes encoding histone
      binding factors (NAP1, ASF1, and a subunit of CAF-I) and SNF2-like DEAD/H ATPases
      (SNF2, ISW1, ISW2, CHD1, SWR1, YFR038w, and SPT20) were screened for activity in
      this replication-independent system. ASF1 deletion substantially inhibits
      assembly, a finding consistent with published evidence that Asf1p is a chromatin
      assembly factor. Surprisingly, a strong assembly defect is also associated with
      deletion of CHD1, suggesting that like other SNF2-related groups of nucleic acid
      stimulated ATPases, the chromodomain (CHD) group may contain a member involved in
      chromatin reconstitution. In contrast to the effects of disrupting ASF1 and CHD1,
      deletion of SNF2 is associated with increased resistance of chromatin to
      digestion by micrococcal nuclease. We discuss the possible implications of these
      findings for current understanding of the diversity of mechanisms by which
      chromatin reconstitution and remodeling can be achieved in vivo.

PMID- 14585956
TI  - Reduced fat mass in mice lacking orphan nuclear receptor estrogen-related
      receptor alpha.
AB  - The estrogen-related receptor alpha (ERRalpha) is an orphan member of the
      superfamily of nuclear hormone receptors expressed in tissues that preferentially
      metabolize fatty acids. Despite the molecular characterization of ERRalpha and
      identification of target genes, determination of its physiological function has
      been hampered by the lack of a natural ligand. To further understand the in vivo
      function of ERRalpha, we generated and analyzed Estrra-null (ERRalpha-/-) mutant
      mice. Here we show that ERRalpha-/- mice are viable, fertile and display no gross
      anatomical alterations, with the exception of reduced body weight and peripheral
      fat deposits. No significant changes in food consumption and energy expenditure
      or serum biochemistry parameters were observed in the mutant animals. However,
      the mutant animals are resistant to a high-fat diet-induced obesity. Importantly,
      DNA microarray analysis of gene expression in adipose tissue demonstrates altered
      regulation of several enzymes involved in lipid, eicosanoid, and steroid
      synthesis, suggesting that the loss of ERRalpha might interfere with other
      nuclear receptor signaling pathways. In addition, the microarray study shows
      alteration in the expression of genes regulating adipogenesis as well as energy
      metabolism. In agreement with these findings, metabolic studies showed reduced
      lipogenesis in adipose tissues. This study suggests that ERRalpha functions as a
      metabolic regulator and that the ERRalpha-/- mice provide a novel model for the
      investigation of metabolic regulation by nuclear receptors.

PMID- 14585957
TI  - The DFNA15 deafness mutation affects POU4F3 protein stability, localization, and
      transcriptional activity.
AB  - A mutation in the POU4F3 gene (BRN-3.1, BRN3C) is responsible for DFNA15 (MIM
      602459), autosomal-dominant nonsyndromic hearing loss. POU4F3 is a member of the
      POU family of transcription factors and is essential for inner-ear hair cell
      maintenance. To test the potential effects of the human POU4F3 mutation, we
      performed a series of experiments in cell culture to mimic the human mutation.
      Mutant POU4F3 loses most of its transcriptional activity and most of its ability
      to bind to DNA and does not function in a dominant-negative manner. Moreover,
      whereas wild-type POU4F3 is found exclusively in the nucleus, our studies
      demonstrate that the mutant protein is localized both to the nucleus and the
      cytoplasm. Two nuclear localization signals were identified; both are essential
      for proper nuclear entry of POU4F3 protein. We found that the mutant protein half
      life is longer than that of the wild type. We propose that the combination of
      defects caused by the mutation on the function of the POU4F3 transcription factor
      eventually leads to hair cell morbidity in affected family H members.

PMID- 14585958
TI  - Adhesive and lateral E-cadherin dimers are mediated by the same interface.
AB  - E-cadherin is a transmembrane protein that mediates Ca(2+)-dependent cell-cell
      adhesion. To study cadherin-cadherin interactions that may underlie the adhesive
      process, a recombinant E-cadherin lacking free sulfhydryl groups and its mutants
      with novel cysteines were expressed in epithelial A-431 cells. These cysteine
      mutants, designed according to various structural models of cadherin dimers, were
      constructed to reveal cadherin dimerization by the bifunctional sulfhydryl
      specific cross-linker BM[PE0]3. Cross-linking experiments with the mutants
      containing a cysteine at strand B of their EC1 domains did show cadherin
      dimerization. By their properties these dimers correspond to those which have
      been characterized by co-immunoprecipitation assay. Under standard culture
      conditions the adhesive dimer is a dominant form. Calcium depletion dissociates
      adhesive dimers and promotes the formation of lateral dimers. Our data show that
      both dimers are mediated by the amino-terminal cadherin domain. Furthermore, the
      interfaces involved in both adhesive and lateral dimerization appear to be the
      same. The coexistence of the structurally identical adhesive and lateral dimers
      suggests some flexibility of the extracellular cadherin region.

PMID- 14585959
TI  - Deletion of ghrelin impairs neither growth nor appetite.
AB  - Pharmacological studies show that ghrelin stimulates growth hormone release,
      appetite, and fat deposition, but ghrelin's physiological role in energy
      homeostasis has not been established. Ghrelin was also proposed to regulate
      leptin and insulin release and to be important for the normal function of
      stomach, heart, kidney, lung, testis, and placenta. To help determine a definable
      physiological role for ghrelin, we generated ghrelin-null mice. In contrast to
      predictions made from the pharmacology of ghrelin, ghrelin-null mice are not
      anorexic dwarfs; their size, growth rate, food intake, body composition,
      reproduction, gross behavior, and tissue pathology are indistinguishable from
      wild-type littermates. Fasting produces identical decreases in serum leptin and
      insulin in null and wild-type mice. Ghrelin-null mice display normal responses to
      starvation and diet-induced obesity. As in wild-type mice, the administration of
      exogenous ghrelin stimulates appetite in null mice. Our data show that ghrelin is
      not critically required for viability, fertility, growth, appetite, bone density,
      and fat deposition and not likely to be a direct regulator of leptin and insulin.
      Therefore, antagonists of ghrelin are unlikely to have broad utility as
      antiobesity agents.

PMID- 14585960
TI  - Discrete functions of TRAF1 and TRAF2 in Drosophila melanogaster mediated by c
      Jun N-terminal kinase and NF-kappaB-dependent signaling pathways.
AB  - Two Drosophila tumor necrosis factor receptor-associated factors (TRAF), DTRAF1
      and DTRAF2, are proposed to have similar functions with their mammalian
      counterparts as a signal mediator of cell surface receptors. However, their in
      vivo functions and related signaling pathways are not fully understood yet. Here,
      we show that DTRAF1 is an in vivo regulator of c-Jun N-terminal kinase (JNK)
      pathway in Drosophila melanogaster. Ectopic expression of DTRAF1 in the
      developing eye induced apoptosis, thereby causing a rough-eye phenotype. Further
      genetic interaction analyses revealed that the apoptosis in the eye imaginal disc
      and the abnormal eye morphogenesis induced by DTRAF1 are dependent on JNK and its
      upstream kinases, Hep and DTAK1. In support of these results, DTRAF1-null mutant
      showed a remarkable reduction in JNK activity with an impaired development of
      imaginal discs and a defective formation of photosensory neuron arrays. In
      contrast, DTRAF2 was demonstrated as an upstream activator of nuclear factor
      kappaB (NF-kappaB). Ectopic expression of DTRAF2 induced nuclear translocation of
      two Drosophila NF-kappaBs, DIF and Relish, consequently activating the
      transcription of the antimicrobial peptide genes diptericin, diptericin-like
      protein, and drosomycin. Consistently, the null mutant of DTRAF2 showed immune
      deficiencies in which NF-kappaB nuclear translocation and antimicrobial gene
      transcription against microbial infection were severely impaired. Collectively,
      our findings demonstrate that DTRAF1 and DTRAF2 play pivotal roles in Drosophila
      development and innate immunity by differentially regulating the JNK- and the NF
      kappaB-dependent signaling pathway, respectively.

PMID- 14585961
TI  - Regulation of the human MSH6 gene by the Sp1 transcription factor and alteration
      of promoter activity and expression by polymorphisms.
AB  - Defects in human DNA mismatch repair have been reported to underlie a variety of
      hereditary and sporadic cancer cases. We characterized the structure of the MSH6
      promoter region to examine the mechanisms of transcriptional regulation of the
      MSH6 gene. The 5'-flanking region of the MSH6 gene was found to contain seven
      functional Sp1 transcription factor binding sites that each bind Sp1 and Sp3 and
      contribute to promoter activity. Transcription did not appear to require a TATA
      box and resulted in multiple start sites, including two major start sites and at
      least nine minor start sites. Three common polymorphisms were identified in the
      promoter region (-557 T-->G, -448 G-->A, and -159 C-->T): the latter two were
      always associated, and each of these functionally inactivated a different Sp1
      site. The polymorphic allele -448 A -159 T was demonstrated to be a common
      Caucasian polymorphism found in 16% of Caucasians and resulted in a five-Sp1-site
      promoter that had 50% less promoter activity and was more sensitive to
      inactivation by DNA methylation than the more common seven Sp1 site promoter
      allele, which was only partially inactivated by DNA methylation. In cell lines,
      this five-Sp1-site polymorphism resulted in reduced MSH6 expression at both the
      mRNA and protein level. An additional 2% of Caucasians contained another
      polymorphism, -210 C-->T, which inactivated a single Sp1 site that also
      contributes to promoter activity.

PMID- 14585962
TI  - Phosphorylation-elicited quaternary changes of GA binding protein in
      transcriptional activation.
AB  - Enrichment of nicotinic acetylcholine receptors (nAChR) on the tip of the
      subjunctional folds of the postsynaptic membrane is a central event in the
      development of the vertebrate neuromuscular junction. This is attained, in part,
      through a selective transcription in the subsynaptic nuclei, and it has recently
      been shown that the GA binding protein (GABP) plays an important role in this
      compartmentalized expression. The neural factor heregulin (HRG) activates nAChR
      transcription in cultured cells by stimulating a signaling cascade of protein
      kinases. Hence, it is speculated that GABP becomes activated by phosphorylation,
      but the mechanism has remained elusive. To fully understand the consequences of
      GABP phosphorylation, we examined the effect of heregulin-elicited GABP
      phosphorylation on cellular localization, DNA binding, transcription, and
      mobility. We demonstrate that HRG-elicited phosphorylation dramatically changes
      the transcriptional activity and mobility of GABP. While phosphorylation of
      GABPbeta seems to be dispensable for these changes, phosphorylation of GABPalpha
      is crucial. Using fluorescence resonance energy transfer, we furthermore showed
      that phosphorylation of threonine 280 in GABPalpha triggers reorganizations of
      the quaternary structure of GABP. Taken together, these results support a model
      in which phosphorylation-elicited structural changes of GABP enable engagement in
      certain interactions leading to transcriptional activation.

PMID- 14585964
TI  - Regulation of focal adhesion kinase by its amino-terminal domain through an
      autoinhibitory interaction.
AB  - We have investigated a role for the amino-terminal FERM-like domain of the focal
      adhesion kinase (FAK) as a negative regulator of its own activity and
      phosphorylation state. Deletion of the first 375 amino acids from the amino
      terminus of FAK increases its catalytic activity in vitro, its phosphorylation
      when expressed in mammalian cells, and the phosphorylation of a FAK substrate,
      paxillin. Deletion mutants are phosphorylated in suspension, suggesting that they
      are no longer regulated by adhesion. The amino terminus of FAK can interact with
      the kinase domain of FAK in vitro and in vivo, suggesting that it might act as an
      autoinhibitor of FAK activity. The amino terminus of FAK can act in trans to
      inhibit FAK phosphorylation when expressed in mammalian cells or to directly
      inhibit FAK activity in vitro. Expression of the amino terminus of FAK inhibits
      cell cycle progression in CHO cells, consistent with its inhibition of FAK
      phosphorylation and function in trans. A glutathione S-transferase fusion protein
      containing the cytoplasmic tail of the beta1 integrin stimulates FAK activity in
      vitro, suggesting that FAK could be regulated by molecular interactions with the
      amino terminus. Based on these and previous data, we propose a working model for
      activation of FAK in cell adhesion.

PMID- 14585963
TI  - Pyk2- and Src-dependent tyrosine phosphorylation of PDK1 regulates focal
      adhesions.
AB  - 3-Phosphoinositide-dependent protein kinase 1 (PDK1) is a signal integrator that
      activates the AGC superfamily of serine/threonine kinases. PDK1 is phosphorylated
      on tyrosine by oxidants, although its regulation by agonists that stimulate G
      protein-coupled receptor signaling pathways and the physiological consequences of
      tyrosine phosphorylation in this setting have not been fully identified. We found
      that angiotensin II stimulates the tyrosine phosphorylation of PDK1 in vascular
      smooth muscle in a calcium- and c-Src-dependent manner. The calcium-activated
      tyrosine kinase Pyk2 acts as a scaffold for Src-dependent phosphorylation of PDK1
      on Tyr9, which permits phosphorylation of Tyr373 and -376 by Src. This critical
      function of Pyk2 is further supported by the observation that Pyk2 and tyrosine
      phosphorylated PDK1 colocalize in focal adhesions after angiotensin II
      stimulation. Importantly, infection of smooth muscle cells with a Tyr9 mutant of
      PDK1 inhibits angiotensin II-induced tyrosine phosphorylation of paxillin and
      focal adhesion formation. These observations identify a novel interaction between
      PDK1 and Pyk2 that regulates the integrity of focal adhesions, which are major
      compartments for integrating signals for cell growth, apoptosis, and migration.

PMID- 14585965
TI  - Regulation of T-cell activation by phosphodiesterase 4B2 requires its dynamic
      redistribution during immunological synapse formation.
AB  - Stimulation of T cells through their antigen receptors (TCRs) causes a transient
      increase in the intracellular concentration of cyclic AMP (cAMP). However,
      sustained high levels of cAMP inhibit T-cell responses, suggesting that TCR
      signaling is coordinated with the activation of cyclic nucleotide
      phosphodiesterases (PDEs). The molecular basis of such a pathway is unknown. Here
      we show that TCR-dependent signaling activates PDE4B2 and that this enhances
      interleukin-2 production. Such an effect requires the regulatory N terminus of
      PDE4B2 and correlates with partitioning within lipid rafts, early targeting of
      this PDE to the immunological synapse, and subsequent accumulation in the
      antipodal pole of the T cell as activation proceeds.

PMID- 14585966
TI  - Akt phosphorylation of serine 21 on Pak1 modulates Nck binding and cell
      migration.
AB  - The p21-activated protein kinases (Paks) regulate cellular proliferation,
      differentiation, transformation, and survival through multiple downstream
      signals. Paks are activated directly by the small GTPases Rac and Cdc42 and
      several protein kinases including Akt and PDK-1. We found that Akt phosphorylated
      and modestly activated Pak1 in vitro. The major site phosphorylated by Akt on
      Pak1 mapped to serine 21, a site originally shown to be weakly autophosphorylated
      on Pak1 when Cdc42 or Rac activates it. A peptide derived from the region
      surrounding serine 21 was a substrate for Akt but not Pak1 in vitro, and Akt
      stimulated serine 21 phosphorylation on the full-length Pak1 much better than Rac
      did. The adaptor protein Nck binds Pak near serine 21, and its association is
      regulated by phosphorylation of this site. We found that either treatment of Pak1
      in vitro with Akt or coexpression of constitutively active Akt with Pak1 reduced
      Nck binding to Pak1. In HeLa cells, green fluorescent protein-tagged Pak1 was
      concentrated at focal adhesions and was released when Akt was cotransfected. A
      peptide containing the Nck binding site of Pak1 fused to a portion of human
      immunodeficiency virus Tat to allow it to enter cells was used to test the
      functional importance of Nck/Pak binding in Akt-stimulated cell migration. This
      Tat-Nck peptide reduced Akt-stimulated cell migration. Together, these data
      suggest that Akt modulates the association of Pak with Nck to regulate cell
      migration.

PMID- 14585968
TI  - Sox3 is required for gonadal function, but not sex determination, in males and
      females.
AB  - Sox3 is expressed in developing gonads and in the brain. Evolutionary evidence
      suggests that the X-chromosomal Sox3 gene may be the ancestral precursor of Sry,
      a sex-determining gene, and Sox3 has been proposed to play a role in sex
      determination. However, patients with mutations in SOX3 exhibit normal gonadal
      determination but are mentally retarded and have short stature secondary to
      growth hormone (GH) deficiency. We used Cre-LoxP targeted mutagenesis to delete
      Sox3 from mice. Null mice of both sexes had no overt behavioral deficits and
      exhibited normal GH gene expression. Low body weight was observed for some mice;
      overgrowth and misalignment of the front teeth was observed consistently. Female
      Sox3 null mice (-/-) developed ovaries but had excess follicular atresia,
      ovulation of defective oocytes, and severely reduced fertility. Pituitary
      (luteinizing hormone and follicle-stimulating hormone) and uterine functions were
      normal in females. Hemizygous male null mice (-/Y) developed testes but were
      hypogonadal. Testis weight was reduced by 42%, and there was extensive Sertoli
      cell vacuolization, loss of germ cells, reduced sperm counts, and disruption of
      the seminiferous tubules. We conclude that Sox3 is not required for gonadal
      determination but is important for normal oocyte development and male testis
      differentiation and gametogenesis.

PMID- 14585967
TI  - IkappaB kinase-independent IkappaBalpha degradation pathway: functional NF-kappaB
      activity and implications for cancer therapy.
AB  - Antiapoptotic activity of NF-kappaB in tumors contributes to acquisition of
      resistance to chemotherapy. Degradation of IkappaB is a seminal step in
      activation of NF-kappaB. The IkappaB kinases, IKK1 and IKK2, have been implicated
      in both IkappaB degradation and subsequent modifications of NFkappaB. Using mouse
      embryo fibroblasts (MEFs) devoid of both IKK1 and IKK2 genes (IKK1/2(-/-)), we
      document a novel IkappaB degradation mechanism. We show that this degradation
      induced by a chemotherapeutic agent, doxorubicin (DoxR), does not require the
      classical serine 32 and 36 phosphorylation or the PEST domain of IkappaBalpha.
      Degradation of IkappaBalpha is partially blocked by phosphatidylinositol 3-kinase
      inhibitor LY294002 and is mediated by the proteasome. Free NF-kappaB generated by
      DoxR-induced IkappaB degradation in IKK1/2(-/-) cells is able to activate
      chromatin based NF-kappaB reporter gene and expression of the endogenous target
      gene, IkappaBalpha. These results also imply that modification of NF-kappaB by
      IKK1 or IKK2 either prior or subsequent to its release from IkappaB is not
      essential for NF-kappaB-mediated gene expression at least in response to DNA
      damage. In addition, DoxR-induced cell death in IKK1/2(-/-) MEFs is enhanced by
      simultaneous inhibition of NF-kappaB activation by blocking the proteasome
      activity. These results reveal an additional pathway of activating NF-kappaB
      during the course of anticancer therapy and provide a mechanistic basis for the
      observation that proteasome inhibitors could be used as adjuvants in
      chemotherapy.

PMID- 14585969
TI  - EphA3 null mutants do not demonstrate motor axon guidance defects.
AB  - Motor axon projections are topographically ordered. Medial motor column axons
      project to axial muscles, whereas lateral motor column axons project to limb
      muscles and, along the rostrocaudal axis of the animal, the more rostral motor
      neuron pools project to more rostral muscle targets. We have shown that EphA3 is
      specifically expressed in the developing medial motor column and have postulated
      that EphA3 might be responsible for directing their axons to axial muscle
      targets. This hypothesis was supported by our demonstration that EphA3 can direct
      retinal ganglion cell axon targeting and by studies of ephrin-A5(-/-) mutants
      that show that EphA receptor signaling controls the topographic innervation of
      the acromiotrapezius. To test the role of EphA3 in motor axon guidance, we
      generated an EphA3 null mutant. Retrograde labeling studies in EphA3(-/-) embryos
      and adults indicate that, contrary to our predictions, EphA3 is not necessary to
      direct motor axons to axial muscle targets. Our results also demonstrate that
      ephrin A5's ability to direct topographic innervation of the acromiotrapezius
      must be mediated through EphA receptors other than, or in addition to, EphA3.

PMID- 14585970
TI  - A human globin enhancer causes both discrete and widespread alterations in
      chromatin structure.
AB  - Gene activation requires alteration of chromatin structure to facilitate active
      transcription complex formation at a gene promoter. Nucleosome remodeling
      complexes and histone modifying complexes each play unique and interdependent
      roles in bringing about these changes. The role of distant enhancers in these
      structural alterations is not well understood. We studied nucleosome remodeling
      and covalent histone modification mediated by the beta-globin locus control
      region HS2 enhancer at nucleosome-level resolution throughout a 5.5-kb globin
      gene model locus in vivo in K562 cells. We compared the transcriptionally active
      locus to one in which HS2 was inactivated by mutations in the core NF-E2 sites.
      In contrast to inactive templates, nucleosomes were mobilized in discrete areas
      of the active locus, including the HS2 core and the proximal promoter. Large
      differences in restriction enzyme accessibility between the active and inactive
      templates were limited to the regions of nucleosome mobilization, which subsumed
      the DNase I hypersensitive sites. In contrast to this discrete pattern, histone
      H3 and H4 acetylation and H3 K4 methylation were elevated across the entire
      active locus, accompanied by depletion of linker histone H1. The coding region of
      the gene differed from the regulatory regions, demonstrating both nucleosome
      mobilization and histone hyperacetylation, but lacked differences in restriction
      enzyme accessibility between transcriptionally active and inactive genes. Thus,
      although the histone modification pattern we observe is consistent with the
      spreading of histone modifying activity from the distant enhancer, the pattern of
      nucleosome mobilization is more compatible with direct contact between an
      enhancer and promoter.

PMID- 14585971
TI  - Identification of HiNF-P, a key activator of cell cycle-controlled histone H4
      genes at the onset of S phase.
AB  - At the G(1)/S phase cell cycle transition, multiple histone genes are expressed
      to ensure that newly synthesized DNA is immediately packaged as chromatin. Here
      we have purified and functionally characterized the critical transcription factor
      HiNF-P, which is required for E2F-independent activation of the histone H4
      multigene family. Using chromatin immunoprecipitation analysis and ligation
      mediated PCR-assisted genomic sequencing, we show that HiNF-P interacts with
      conserved H4 cell cycle regulatory sequences in vivo. Antisense inhibition of
      HiNF-P reduces endogenous histone H4 gene expression. Furthermore, we find that
      HiNF-P utilizes NPAT/p220, a substrate of the cyclin E/cyclin-dependent kinase 2
      (CDK2) kinase complex, as a key coactivator to enhance histone H4 gene
      transcription. The biological role of HiNF-P is reflected by impeded cell cycle
      progression into S phase upon antisense-mediated reduction of HiNF-P levels. Our
      results establish that HiNF-P is the ultimate link in a linear signaling pathway
      that is initiated with the growth factor-dependent induction of cyclin E/CDK2
      kinase activity at the restriction point and culminates in the activation of
      histone H4 genes through HiNF-P at the G(1)/S phase transition.

PMID- 14585972
TI  - Biochemical characterization of the Ran-RanBP1-RanGAP system: are RanBP proteins
      and the acidic tail of RanGAP required for the Ran-RanGAP GTPase reaction?
AB  - RanBP type proteins have been reported to increase the catalytic efficiency of
      the RanGAP-mediated GTPase reaction on Ran. Since the structure of the Ran-RanBP1
      RanGAP complex showed RanBP1 to be located away from the active site, we
      reinvestigated the reaction using fluorescence spectroscopy under pre-steady
      state conditions. We can show that RanBP1 indeed does not influence the rate
      limiting step of the reaction, which is the cleavage of GTP and/or the release of
      product P(i). It does, however, influence the dynamics of the Ran-RanGAP
      interaction, its most dramatic effect being the 20-fold stimulation of the
      already very fast association reaction such that it is under diffusion control
      (4.5 x 10(8) M(-1) s(-1)). Having established a valuable kinetic system for the
      interaction analysis, we also found, in contrast to previous findings, that the
      highly conserved acidic C-terminal end of RanGAP is not required for the switch
      off reaction. Rather, genetic experiments in Saccharomyces cerevisiae demonstrate
      a profound effect of the acidic tail on microtubule organization during mitosis.
      We propose that the acidic tail of RanGAP is required for a process during
      mitosis.

PMID- 14585973
TI  - Distinct cysteine residues in Keap1 are required for Keap1-dependent
      ubiquitination of Nrf2 and for stabilization of Nrf2 by chemopreventive agents
      and oxidative stress.
AB  - A common feature of diverse chemopreventive agents is the ability to activate
      expression of a genetic program that protects cells from reactive chemical
      species that, if left unchecked, would cause mutagenic DNA damage. The bZIP
      transcription factor Nrf2 has emerged as a key regulator of this cancer
      preventive genetic program. Nrf2 is normally sequestered in the cytoplasm by a
      protein known as Keap1. Chemopreventive agents allow Nrf2 to escape from Keap1
      mediated repression, although the molecular mechanism(s) responsible for
      activation of Nrf2 is not understood. In this report, we demonstrate that Keap1
      does not passively sequester Nrf2 in the cytoplasm but actively targets Nrf2 for
      ubiquitination and degradation by the proteosome under basal culture conditions.
      We have identified two critical cysteine residues in Keap1, C273 and C288, that
      are required for Keap1-dependent ubiquitination of Nrf2. Both sulforaphane, a
      chemopreventive isothiocyanate, and oxidative stress enable Nrf2 to escape Keap1
      dependent degradation, leading to stabilization of Nrf2, increased nuclear
      localization of Nrf2, and activation of Nrf2-dependent cancer-protective genes.
      We have identified a third cysteine residue in Keap1, C151, that is uniquely
      required for inhibition of Keap1-dependent degradation of Nrf2 by sulforaphane
      and oxidative stress. This cysteine residue is also required for a novel
      posttranslational modification to Keap1 that is induced by oxidative stress. We
      propose that Keap1 is a component of a novel E3 ubiquitin ligase complex that is
      specifically targeted for inhibition by both chemopreventive agents and oxidative
      stress.

PMID- 14585974
TI  - Role of the inhibitory DNA-binding surface of human TATA-binding protein in
      recruitment of human TFIIB family members.
AB  - TATA box recognition by TATA-binding protein (TBP) is a key step in
      transcriptional initiation complex assembly on TATA-box-containing RNA polymerase
      (Pol) II and III promoters. This process is inhibited by the inhibitory DNA
      binding (IDB) surface on the human TBP core domain (TBP(CORE)) and is stimulated
      by promoter-specific basal transcription factors, such as two human TFIIB family
      members, the Pol II factor TFIIB and the Pol III factor Brf2, which is required
      for transcription from TATA-box-containing Pol III promoters. In contrast, the
      third TFIIB family member, Brf1, which is required for transcription from TATA
      less Pol III promoters, does not stimulate TBP binding to the TATA box. We show
      here that in addition to its role in regulating TBP binding to a TATA box, the
      TBP IDB surface is unexpectedly involved in TBP association with all three TFIIB
      family members. Interestingly, the loss of IDB function has specific and diverse
      effects on each TFIIB family member. Indeed, the IDB and prototypical TFIIB
      contact surfaces of TBP, which lie on opposite sides of the TBP(CORE), cooperate
      to form the wild-type TFIIB-TBP-TATA box complex. These results reveal how,
      through differential usage of opposite surfaces of the TBP(CORE), TBP can achieve
      versatility in the assembly of Pol II and Pol III promoter complexes with TFIIB
      family proteins.

PMID- 14585975
TI  - p73alpha regulation by Chk1 in response to DNA damage.
AB  - The checkpoint kinase 1 (Chk1) is an essential component of the DNA damage
      checkpoint. Previous studies have demonstrated an indispensable role for the p53
      related transcription factor p73alpha in DNA damage-induced apoptosis. Here, we
      provide evidence that p73alpha is a target of Chk1. We found that endogenous
      p73alpha is serine phosphorylated by endogenous Chk1 upon DNA damage, which is a
      mechanism required for the apoptotic-inducing function of p73alpha. Consistent
      with this, we discovered that endogenous p73alpha interacts with Chk1 and is
      phosphorylated by Chk1 at serine 47 in vitro and in vivo. In contrast, Chk2 does
      not phosphorylate p73alpha in vitro. Moreover, mutation of serine 47 abolishes
      both Chk1-dependent phosphorylation of p73alpha upon DNA damage in vivo and the
      ability of Chk1 to upregulate the transactivation capacity of p73alpha. Our data
      indicate a novel biochemical pathway through which the p73alpha proapoptotic
      function requires DNA damage-triggered p73alpha phosphorylation by Chk1.

PMID- 14585977
TI  - Identification and characterization of a Candida albicans mating pheromone.
AB  - Candida albicans, the most prevalent fungal pathogen of humans, has recently been
      shown to undergo mating. Here we describe a mating pheromone produced by C.
      albicans alpha cells and show that the gene which encodes it (MFalpha) is
      required for alpha cells, but not a cells, to mate. We also identify the receptor
      for this mating pheromone as the product of the STE2 gene and show that this gene
      is required for the mating of a cells, but not alpha cells. Cells of the a mating
      type respond to the alpha mating pheromone by producing long polarized
      projections, similar to those observed in bona fide mating mixtures of C.
      albicans a and alpha cells. During this process, transcription of approximately
      62 genes is induced. Although some of these genes correspond to those induced in
      Saccharomyces cerevisiae by S. cerevisiae alpha-factor, most are specific to the
      C. albicans pheromone response. The most surprising class encode cell surface and
      secreted proteins previously implicated in virulence of C. albicans in a mouse
      model of disseminated candidiasis. This observation suggests that aspects of cell
      cell communication in mating may have been evolutionarily adopted for host
      pathogen interactions in C. albicans.

PMID- 14585976
TI  - Retinoblastoma tumor suppressor: analyses of dynamic behavior in living cells
      reveal multiple modes of regulation.
AB  - The retinoblastoma tumor suppressor, RB, assembles multiprotein complexes to
      mediate cell cycle inhibition. Although many RB binding partners have been
      suggested to underlie these functions, the validity of these interactions on the
      behavior of RB complexes in living cells has not been investigated. Here, we
      studied the dynamic behavior of RB by using green fluorescent protein-RB fusion
      proteins. Although these proteins were universally nuclear, phosphorylation or
      oncoprotein binding mediated their active exclusion from the nucleolus. In vivo
      imaging approaches revealed that RB exists in dynamic equilibrium between a
      highly mobile and a slower diffusing species, and genetic lesions associated with
      tumorigenesis increased the fraction of RB in a highly mobile state. The RB
      complexes dictating cell cycle arrest were surprisingly dynamic and harbored a
      relatively short residence time on chromatin. In contrast, this rapid exchange
      was attenuated in cells that are hypersensitive to RB, suggesting that
      responsiveness may inversely correlate with mobility. The stability of RB
      dynamics within the cell was additionally modified by the presence and function
      of critical corepressors. Last, the RB-assembled complexes present in living
      cells were primarily associated with E2F binding sites in chromatin. In contrast
      to RB, E2F1 consistently maintained a stable association with E2F sites
      regardless of cell type. Together, these results elucidate the kinetic framework
      of RB tumor suppressor action in transcriptional repression and cell cycle
      regulation.

PMID- 14585978
TI  - The Ku heterodimer performs separable activities at double-strand breaks and
      chromosome termini.
AB  - The Ku heterodimer functions at two kinds of DNA ends: telomeres and double
      strand breaks. The role that Ku plays at these two classes of termini must be
      distinct, because Ku is required for accurate and efficient joining of double
      strand breaks while similar DNA repair events are normally prohibited at
      chromosome ends. Toward defining these functional differences, we have identified
      eight mutations in the large subunit of the Saccharomyces cerevisiae Ku
      heterodimer (YKU80) which retain the ability to repair double-strand breaks but
      are severely impaired for chromosome end protection. Detailed characterization of
      these mutations, referred to as yku80(tel) alleles, has revealed that Ku performs
      functionally distinct activities at subtelomeric chromatin versus the end of the
      chromosome, and these activities are separable from Ku's role in telomere length
      regulation. While at the chromosome terminus, we propose that Ku participates in
      two different activities: it facilitates telomerase-mediated G-strand synthesis,
      thereby contributing to telomere length regulation, and it separately protects
      against resection of the C-strand, thereby contributing to protection of
      chromosome termini. Furthermore, we propose that the Ku heterodimer performs
      discrete sets of functions at chromosome termini and at duplex subtelomeric
      chromatin, via separate interactions with these two locations. Based on homology
      modeling with the human Ku structure, five of the yku80(tel) alleles mutate
      residues that are conserved between the yeast and human Ku80 proteins, suggesting
      that these mutations probe activities that are shared between yeast and humans.

PMID- 14585979
TI  - The Iroquois homeobox gene Irx2 is not essential for normal development of the
      heart and midbrain-hindbrain boundary in mice.
AB  - The Iroquois homeobox (Irx) genes have been implicated in the specification and
      patterning of several organs in Drosophila and several vertebrate species.
      Misexpression studies of chick, Xenopus, and zebra fish embryos have demonstrated
      that Irx genes are involved in the specification of the midbrain-hindbrain
      boundary. All six murine Irx genes are expressed in the developing heart,
      suggesting that they might possess distinct functions during heart development,
      and a role for Irx4 in normal heart development has been recently demonstrated by
      gene-targeting experiments. Here we describe the generation and phenotypic
      analysis of an Irx2-deficient mouse strain. By targeted insertion of a lacZ
      reporter gene into the Irx2 locus, we show that lacZ expression reproduces most
      of the endogenous Irx2 expression pattern. Despite the dynamic expression of Irx2
      in the developing heart, nervous system, and other organs, Irx2-deficient mice
      are viable, are fertile, and appear to be normal. Although chick Irx2 has been
      implicated in the development of the midbrain-hindbrain region, we show that Irx2
      deficient mice develop a normal midbrain-hindbrain boundary. Furthermore, Irx2
      deficient mice have normal cardiac morphology and function. Functional
      compensation by other Irx genes might account for the absence of a phenotype in
      Irx2-deficient mice. Further studies of mutant mice of other Irx genes as well as
      compound mutant mice will be necessary to uncover the functional roles of these
      evolutionarily conserved transcriptional regulators in development and disease.

PMID- 14585980
TI  - Cardiomyocyte-specific endothelin A receptor knockout mice have normal cardiac
      function and an unaltered hypertrophic response to angiotensin II and
      isoproterenol.
AB  - Even though endothelin is recognized as an important vasoregulatory molecule, the
      roles of endothelin receptors in specific cell types are not yet fully
      understood. Mice with a null mutation in endothelin A receptor gene (ET(A)) or in
      the gene of its ligand (endothelin 1) die neonatally due to craniofacial and
      cardiac abnormalities. This early lethality has in the past hindered studies on
      the role of endothelin in cardiovascular physiology and pathophysiology. To
      overcome this obstacle, we utilized the cre/loxP technology to generate mice in
      which the ET(A) gene could be deleted specifically in cardiomyocytes. The cre
      recombinase transgene driven by the alpha-myosin heavy-chain promoter deleted the
      floxed ET(A) allele specifically in the hearts of these mice, resulting in a 78%
      reduction in cardiac ET(A) mRNA level compared to wild-type controls.
      Cardiomyocyte-specific ET(A) knockout animals are viable and exhibit normal
      growth, cardiac anatomy, and cardiac contractility, as assessed by
      echocardiography. In addition, these animals exhibit hypertrophic and contractile
      responses to 10-day infusion of angiotensin II or isoproterenol similar to those
      observed in control animals. These results indicate that in adult mice cardiac
      ET(A) receptors are not necessary for either baseline cardiac function or stress
      induced response to angiotensin II or isoproterenol.

PMID- 14585981
TI  - Neurons expressing the highest levels of gamma-synuclein are unaffected by
      targeted inactivation of the gene.
AB  - Homologous recombination in ES cells was employed to generate mice with targeted
      deletion of the first three exons of the gamma-synuclein gene. Complete
      inactivation of gene expression in null mutant mice was confirmed on the mRNA and
      protein levels. Null mutant mice are viable, are fertile, and do not display
      evident phenotypical abnormalities. The effects of gamma-synuclein deficiency on
      motor and peripheral sensory neurons were studied by various methods in vivo and
      in vitro. These two types of neurons were selected because they both express high
      levels of gamma-synuclein from the early stages of mouse embryonic development
      but later in the development they display different patterns of intracellular
      compartmentalization of the protein. We found no difference in the number of
      neurons between wild-type and null mutant animals in several brain stem motor
      nuclei, in lumbar dorsal root ganglia, and in the trigeminal ganglion. The
      survival of gamma-synuclein-deficient trigeminal neurons in various culture
      conditions was not different from that of wild-type neurons. There was no
      difference in the numbers of myelinated and nonmyelinated fibers in the saphenous
      nerves of these animals, and sensory reflex thresholds were also intact in gamma
      synuclein null mutant mice. Nerve injury led to similar changes in sensory
      function in wild-type and mutant mice. Taken together, our data suggest that like
      alpha-synuclein, gamma-synuclein is dispensable for the development and function
      of the nervous system.

PMID- 14585982
TI  - The 5' untranslated region and Gag product of Idefix, a long terminal repeat
      retrotransposon from Drosophila melanogaster, act together to initiate a switch
      between translated and untranslated states of the genomic mRNA.
AB  - Idefix is a long terminal repeat (LTR)-retrotransposon present in Drosophila
      melanogaster which shares similarities with vertebrates retroviruses both in its
      genomic arrangement and in the mechanism of transposition. Like in retroviruses,
      its two LTRs flank a long 5' untranslated region (5'UTR) and three open reading
      frames referred to as the gag, pol, and env genes. Here we report that its 5'UTR,
      located upstream of the gag gene, can fold into highly structured domains that
      are known to be incompatible with efficient translation by ribosome scanning.
      Using dicistronic plasmids analyzed by both (i) in vitro transcription and
      translation in rabbit reticulocyte or wheat germ lysates and (ii) in vivo
      expression in transgenic flies, we show that the 5'UTR of Idefix exhibits an
      internal ribosome entry site (IRES) activity that is able to promote translation
      of a downstream cistron in a cap-independent manner. The functional state of this
      novel IRES depends on eukaryotic factors that are independent of their host
      origin. However, in vivo, its function can be down-regulated by trans-acting
      factors specific to tissues or developmental stages of its host. We identify one
      of these trans-acting factors as the Gag protein encoded by Idefix itself. Our
      data support a model in which nascent Gag is able to block translation initiated
      from the viral mRNA and thus its own translation. These data highlight the fact
      that LTR-retrotransposons may autoregulate their replication cycle through their
      Gag production.

PMID- 14585983
TI  - Female lethality and apoptosis of spermatocytes in mice lacking the UBR2
      ubiquitin ligase of the N-end rule pathway.
AB  - Substrates of the ubiquitin-dependent N-end rule pathway include proteins with
      destabilizing N-terminal residues. UBR1(-/-) mice, which lacked the pathway's
      ubiquitin ligase E3alpha, were viable and retained the N-end rule pathway. The
      present work describes the identification and analysis of mouse UBR2, a homolog
      of UBR1. We demonstrate that the substrate-binding properties of UBR2 are highly
      similar to those of UBR1, identifying UBR2 as the second E3 of the mammalian N
      end rule pathway. UBR2(-/-) mouse strains were constructed, and their viability
      was found to be dependent on both gender and genetic background. In the strain
      129 (inbred) background, the UBR2(-/-) genotype was lethal to most embryos of
      either gender. In the 129/B6 (mixed) background, most UBR2(-/-) females died as
      embryos, whereas UBR2(-/-) males were viable but infertile, owing to the
      postnatal degeneration of the testes. The gross architecture of UBR2(-/-) testes
      was normal and spermatogonia were intact as well, but UBR2(-/-) spermatocytes
      were arrested between leptotene/zygotene and pachytene and died through
      apoptosis. A conspicuous defect of UBR2(-/-) spermatocytes was the absence of
      intact synaptonemal complexes. We conclude that the UBR2 ubiquitin ligase and,
      hence, the N-end rule pathway are required for male meiosis and spermatogenesis
      and for an essential aspect of female embryonic development.

PMID- 14585984
TI  - Functional characterization of a novel promoter element required for an innate
      immune response in Drosophila.
AB  - Innate immune reactions are crucial processes of metazoans to protect the
      organism against overgrowth of faster replicating microorganisms. Drosophila
      melanogaster is a precious model for genetic and molecular studies of the innate
      immune system. In response to infection, the concerted action of a battery of
      antimicrobial peptides ensures efficient killing of the microbes. The induced
      gene expression relies on translocation of the Drosophila Rel transcription
      factors Relish, Dif, and Dorsal to the nucleus where they bind to kappaB-like
      motifs in the promoters of the inducible genes. We have identified another
      putative promoter element, called region 1 (R1), in a number of antimicrobial
      peptide genes. Site-directed mutagenesis of the R1 site diminished Cecropin A1
      (CecA1) expression in transgenic Drosophila larvae and flies. Infection of flies
      induced a nuclear R1-binding activity that was unrelated to the kappaB-binding
      activity in the same extracts. Although the R1 motif was required for Rel protein
      mediated CecA1 expression in cotransfection experiments, our data argue against
      it being a direct target for the Drosophila Rel proteins. We propose that the R1
      and kappaB motifs are targets for distinct regulatory complexes that act in
      concert to promote high levels of antimicrobial peptide gene expression in
      response to infection.

PMID- 14585985
TI  - Poly(ADP-ribose) polymerase 1 and Ste20-like kinase hKFC act as transcriptional
      repressors for gamma-2 herpesvirus lytic replication.
AB  - The replication and transcription activator (RTA) of gamma-2 herpesvirus is
      sufficient to drive the entire virus lytic cycle. Hence, the control of RTA
      activity should play an important role in the maintenance of viral latency. Here,
      we demonstrate that cellular poly(ADP-ribose) polymerase 1 (PARP-1) and Ste20
      like kinase hKFC interact with the serine/threonine-rich region of gamma-2
      herpesvirus RTA and that these interactions efficiently transfer poly(ADP-ribose)
      and phosphate units to RTA. Consequently, these modifications strongly repressed
      RTA-mediated transcriptional activation by inhibiting its recruitment onto the
      promoters of virus lytic genes. Conversely, the genetic ablation of PARP-1 and
      hKFC interaction or the knockout of the PARP-1 gene and activity considerably
      enhanced gamma-2 herpesvirus lytic replication. Thus, this is the first
      demonstration that cellular PARP-1 and hKFC act as molecular sensors to regulate
      RTA activity and thereby, herpesvirus latency.

PMID- 14585986
TI  - Self-association of Gata1 enhances transcriptional activity in vivo in zebra fish
      embryos.
AB  - Gata1 is a prototype transcription factor that regulates hematopoiesis, yet the
      molecular mechanisms by which Gata1 transactivates its target genes in vivo
      remain unclear. We previously showed, in transgenic zebra fish, that Gata1
      autoregulates its own expression. In this study, we characterized the molecular
      mechanisms for this autoregulation by using mutations in the Gata1 protein which
      impair autoregulation. Of the tested mutations, replacement of six lysine
      residues with alanine (Gata1KA6), which inhibited self-association activity of
      Gata1, reduced the Gata1-dependent induction of reporter gene expression driven
      by the zebra fish gata1 hematopoietic regulatory domain (gata1 HRD). Furthermore,
      overexpression of wild-type Gata1 but not Gata1KA6 rescued the expression of
      Gata1 downstream genes in vlad tepes, a germ line gata1 mutant fish.
      Interestingly, both GATA sites in the double GATA motif in gata1 HRD were
      critical for the promoter activity and for binding of the self-associated Gata1
      complex, whereas only the 3'-GATA site was required for Gata1 monomer binding.
      These results thus provide the first in vivo evidence that the ability of Gata1
      to self-associate critically contributes to the autoregulation of the gata1 gene.

PMID- 14585987
TI  - The p38 mitogen-activated protein kinase pathway links the DNA mismatch repair
      system to the G2 checkpoint and to resistance to chemotherapeutic DNA-methylating
      agents.
AB  - Although human cells exposed to DNA-methylating agents undergo mismatch repair
      (MMR)-dependent G(2) arrest, the basis for the linkage between MMR and the G(2)
      checkpoint is unclear. We noted that mitogen-activated protein kinase p38alpha
      was activated in MMR-proficient human glioma cells exposed to the
      chemotherapeutic methylating agent temozolomide (TMZ) but not in paired cells
      made MMR deficient by expression of a short inhibitory RNA (siRNA) targeted to
      the MMR protein Mlh1. Furthermore, activation of p38alpha in MMR-proficient cells
      was associated with nuclear inactivation of the cell cycle regulator Cdc25C
      phosphatase and its downstream target Cdc2 and with activation of the G(2)
      checkpoint, actions which were suppressed by the p38alpha/beta inhibitors
      SB203580 and SB202590 or by expression of a p38alpha siRNA. Finally,
      pharmacologic or genetic inhibition of p38alpha increased the sensitivity of MMR
      proficient cells to the cytotoxic actions of TMZ by increasing the percentage of
      cells that underwent mitotic catastrophe as a consequence of G(2) checkpoint
      bypass. These results suggest that p38alpha links DNA MMR to the G(2) checkpoint
      and to resistance to chemotherapeutic DNA-methylating agents. The p38 pathway may
      therefore represent a new target for the development of agents to sensitize tumor
      cells to chemotherapeutic methylating agents.

PMID- 14585988
TI  - The mechanism of nucleotide incorporation by human DNA polymerase eta differs
      from that of the yeast enzyme.
AB  - DNA polymerase eta (Poleta) catalyzes the efficient and accurate synthesis of DNA
      opposite cyclobutane pyrimidine dimers, and inactivation of Poleta in humans
      causes the cancer-prone syndrome, the variant form of xeroderma pigmentosum. Pre
      steady-state kinetic studies of yeast Poleta have indicated that the low level of
      fidelity of this enzyme results from a poorly discriminating induced-fit
      mechanism. Here we examine the mechanistic basis of the low level of fidelity of
      human Poleta. Because the human and yeast enzymes behave similarly under steady
      state conditions, we expected these enzymes to utilize similar mechanisms of
      nucleotide incorporation. Surprisingly, however, we find that human Poleta
      differs from the yeast enzyme in several important respects. The human enzyme has
      a 50-fold-faster rate of nucleotide incorporation than the yeast enzyme but binds
      the nucleotide with an approximately 50-fold-lower level of affinity. This lower
      level of binding affinity might provide a means of regulation whereby the human
      enzyme remains relatively inactive except when the cellular deoxynucleoside
      triphosphate concentrations are high, as may occur during DNA damage, thereby
      avoiding the mutagenic consequences arising from the inadvertent action of this
      enzyme during normal DNA replication.

PMID- 14585989
TI  - The FACT complex travels with elongating RNA polymerase II and is important for
      the fidelity of transcriptional initiation in vivo.
AB  - The FACT complex facilitates transcription on chromatin templates in vitro, and
      it has been functionally linked to nucleosomes and putative RNA polymerase II
      (Pol II) elongation factors. In Saccharomyces cerevisiae cells, FACT specifically
      associates with active Pol II genes in a TFIIH-dependent manner and travels
      across the gene with elongating Pol II. Conditional inactivation of the FACT
      subunit Spt16 results in increased Pol II density, transcription, and TATA
      binding protein (TBP) occupancy in the 3' portion of certain coding regions,
      indicating that FACT suppresses inappropriate initiation from cryptic promoters
      within coding regions. Conversely, loss of Spt16 activity reduces the association
      of TBP, TFIIB, and Pol II with normal promoters. Thus, FACT is required for wild
      type cells to restrict initiation to normal promoters, thereby ensuring that only
      appropriate mRNAs are synthesized. We suggest that FACT contributes to the
      fidelity of Pol II transcription by linking the processes of initiation and
      elongation.

PMID- 14585990
TI  - TRUSS, a novel tumor necrosis factor receptor 1 scaffolding protein that mediates
      activation of the transcription factor NF-kappaB.
AB  - We describe the cloning and characterization of tumor necrosis factor receptor
      (TNF-R)-associated ubiquitous scaffolding and signaling protein (TRUSS), a novel
      TNF-R1-interacting protein of 90.7 kDa. TRUSS mRNA was ubiquitously expressed in
      mouse tissues but was enriched in heart, liver, and testis. Co
      immunoprecipitation experiments showed that TRUSS was constitutively associated
      with unligated TNF-R1 and that the complex was relatively insensitive to
      stimulation with TNF-alpha. Deletion mutagenesis of TNF-R1 indicated that TRUSS
      interacts with both the membrane-proximal region and the death domain of TNF-R1.
      In addition, the N-terminal region of TRUSS (residues 1 to 440) contains
      sequences that permit association with the cytoplasmic domain of TNF-R1.
      Transient overexpression of TRUSS activated NF-kappaB and increased NF-kappaB
      activation in response to ligation of TNF-R1. In contrast, a COOH-terminal
      deletion mutant of TRUSS (TRUSS(1-723)) was found to inhibit NF-kappaB activation
      by TNF-alpha. Co-precipitation and co-immunoprecipitation assays revealed that
      TRUSS can interact with TRADD, TRAF2, and components of the IKK complex. These
      findings suggest that TRUSS may serve as a scaffolding protein that interacts
      with TNF-R1 signaling proteins and may link TNF-R1 to the activation of IKK.

PMID- 14585991
TI  - Functional characterization of a testis-specific DNA binding activity at the
      H19/Igf2 imprinting control region.
AB  - The DNA methylation state of the H19/Igf2 imprinting control region (ICR) is
      differentially set during gametogenesis. To identify factors responsible for the
      paternally specific DNA methylation of the ICR, germ line and somatic extracts
      were screened for proteins that bind to the ICR in a germ line-specific manner. A
      specific DNA binding activity that was restricted to the male germ line and
      enriched in neonatal testis was identified. Its three binding sites within the
      ICR are very similar to the consensus sequence for nuclear receptor extended half
      sites. To determine if these binding sites are required for establishment of the
      paternal epigenetic state, a mouse strain in which the three sites were mutated
      was generated. The mutated ICR was able to establish a male-specific epigenetic
      state in sperm that was indistinguishable from that established by the wild-type
      ICR, indicating that these sequences are either redundant or have no function. An
      analysis of the methylated state of the mutant ICR in the soma revealed no
      differences from the wild-type ICR but did uncover in both mutant and wild-type
      chromosomes a significant relaxation in the stringency of the methylated state of
      the paternal allele and the unmethylated state of the maternal allele in neonatal
      and adult tissues.

PMID- 14585992
TI  - The papillomavirus E8-E2C protein represses DNA replication from extrachromosomal
      origins.
AB  - Carcinogenic DNA viruses such as high-risk human papillomaviruses (HPV) and
      Epstein-Barr-Virus (EBV) replicate during persistent infections as low-copy
      number plasmids. EBV DNA replication is restricted by host cell replication
      licensing mechanisms. In contrast, copy number control of HPV genomes is not
      under cellular control but involves the viral sequence-specific DNA-binding E2
      activator and E8-E2C repressor proteins. Analysis of HPV31 mutant genomes
      revealed that residues outside of the DNA-binding/dimerization domain of E8-E2C
      limit viral DNA replication, indicating that binding site competition or
      heterodimerization among E2 and E8-E2C proteins does not contribute to copy
      number control. Domain swap experiments demonstrated that the amino-terminal 21
      amino acids of E8-E2C represent a novel, transferable DNA replication repressor
      domain, whose activity requires conserved lysine and tryptophan residues.
      Furthermore, E8-E2C (1-21)-GAL4 fusion proteins inhibited the replication of the
      plasmid origin of replication of EBV, suggesting that E8-E2C functions as a
      general replication repressor of extrachromosomal origins. This finding could be
      important for the development of novel therapies against persistent DNA tumor
      virus infections.

PMID- 14585993
TI  - Human heterochromatin protein 1 isoforms HP1(Hsalpha) and HP1(Hsbeta) interfere
      with hTERT-telomere interactions and correlate with changes in cell growth and
      response to ionizing radiation.
AB  - Telomeres are associated with the nuclear matrix and are thought to be
      heterochromatic. We show here that in human cells the overexpression of green
      fluorescent protein-tagged heterochromatin protein 1 (GFP-HP1) or nontagged HP1
      isoforms HP1(Hsalpha) or HP1(Hsbeta), but not HP1(Hsgamma), results in decreased
      association of a catalytic unit of telomerase (hTERT) with telomeres. However,
      reduction of the G overhangs and overall telomere sizes was found in cells
      overexpressing any of these three proteins. Cells overexpressing HP1(Hsalpha) or
      HP1(Hsbeta) also display a higher frequency of chromosome end-to-end associations
      and spontaneous chromosomal damage than the parental cells. None of these effects
      were observed in cells expressing mutants of GFP-DeltaHP1(Hsalpha), GFP
      DeltaHP1(Hsbeta), or GFP-DeltaHP1(Hsgamma) that had their chromodomains deleted.
      An increase in the cell population doubling time and higher sensitivity to cell
      killing by ionizing radiation (IR) treatment was also observed for cells
      overexpressing HP1(Hsalpha) or HP1(Hsbeta). In contrast, cells expressing mutant
      GFP-DeltaHP1(Hsalpha) or GFP-DeltaHP1(Hsbeta) showed a decrease in population
      doubling time and decreased sensitivity to IR compared to the parental cells. The
      effects on cell doubling times were paralleled by effects on tumorigenicity in
      mice: overexpression of HP1(Hsalpha) or HP1(Hsbeta) suppressed tumorigenicity,
      whereas expression of mutant HP1(Hsalpha) or HP1(Hsbeta) did not. Collectively,
      the results show that human cells are exquisitely sensitive to the amount of
      HP1(Hsalpha) or HP1(Hsbeta) present, as their overexpression influences telomere
      stability, population doubling time, radioresistance, and tumorigenicity in a
      mouse xenograft model. In addition, the isoform-specific effects on telomeres
      reinforce the notion that telomeres are in a heterochromatinized state.

PMID- 14585995
TI  - Origin of endogenous DNA abasic sites in Saccharomyces cerevisiae.
AB  - Abasic (AP) sites are among the most frequent endogenous lesions in DNA and
      present a strong block to replication. In Saccharomyces cerevisiae, an apn1 apn2
      rad1 triple mutant is inviable because of its incapacity to repair AP sites and
      related 3'-blocked single-strand breaks (M. Guillet and S. Boiteux, EMBO J.
      21:2833, 2002). Here, we investigated the origin of endogenous AP sites in yeast.
      Our results show that the deletion of the UNG1 gene encoding the uracil DNA
      glycosylase suppresses the lethality of the apn1 apn2 rad1 mutant. In contrast,
      inactivation of the MAG1, OGG1, or NTG1 and NTG2 genes encoding DNA glycosylases
      involved in the repair of alkylation or oxidation damages does not suppress
      lethality. Although viable, the apn1 apn2 rad1 ung1 mutant presents growth delay
      due to a G(2)/M checkpoint. These results point to uracil as a critical source of
      the formation of endogenous AP sites in DNA. Uracil can arise in DNA by cytosine
      deamination or by the incorporation of dUMP during replication. Here, we show
      that the overexpression of the DUT1 gene encoding the dUTP pyrophosphatase (Dut1)
      suppresses the lethality of the apn1 apn2 rad1 mutant. Therefore, this result
      points to the dUTP pool as an important source of the formation of endogenous AP
      sites in eukaryotes.

PMID- 14585994
TI  - The death domain kinase RIP1 is essential for tumor necrosis factor alpha
      signaling to p38 mitogen-activated protein kinase.
AB  - The cytokine tumor necrosis factor alpha (TNF-alpha) stimulates the NF-kappaB,
      SAPK/JNK, and p38 mitogen-activated protein (MAP) kinase pathways by recruiting
      RIP1 and TRAF2 proteins to the tumor necrosis factor receptor 1 (TNFR1). Genetic
      studies have revealed that RIP1 links the TNFR1 to the IkappaB kinase (IKK)
      complex, whereas TRAF2 couples the TNFR1 to the SAPK/JNK cascade. In transfection
      studies, RIP1 and TRAF2 stimulate p38 MAP kinase activation, and dominant
      negative forms of RIP1 and TRAF2 inhibit TNF-alpha-induced p38 MAP kinase
      activation. We found TNF-alpha-induced p38 MAP kinase activation and interleukin
      6 (IL-6) production impaired in rip1(-/-) murine embryonic fibroblasts (MEF) but
      unaffected in traf2(-/-) MEF. Yet, both rip1(-/-) and traf2(-/-) MEF exhibit a
      normal p38 MAP kinase response to inducers of osmotic shock or IL-1alpha. Thus,
      RIP1 is a specific mediator of the p38 MAP kinase response to TNF-alpha. These
      studies suggest that TNF-alpha-induced activation of p38 MAP kinase and SAPK/JNK
      pathways bifurcate at the level of RIP1 and TRAF2. Moreover, endogenous RIP1
      associates with the MAP kinase kinase kinase (MAP3K) MEKK3 in TNF-alpha-treated
      cells, and decreased TNF-alpha-induced p38 MAP kinase activation is observed in
      Mekk3(-/-) cells. Taken together, these studies suggest a mechanism whereby RIP1
      may mediate the p38 MAP kinase response to TNF-alpha, by recruiting the MAP3K
      MEKK3.

PMID- 14585997
TI  - Vesicular localization and activity-dependent trafficking of presynaptic choline
      transporters.
AB  - Presynaptic synthesis of acetylcholine (ACh) requires a steady supply of choline,
      acquired by a plasma membrane, hemicholinium-3-sensitive (HC-3) choline
      transporter (CHT). A significant fraction of synaptic choline is recovered from
      ACh hydrolyzed by acetylcholinesterase (AChE) after vesicular release. Although
      antecedent neuronal activity is known to dictate presynaptic CHT activity, the
      mechanisms supporting this regulation are unknown. We observe an exclusive
      localization of CHT to cholinergic neurons and demonstrate that the majority of
      CHTs reside on small vesicles within cholinergic presynaptic terminals in the rat
      and mouse brain. Furthermore, immunoisolation of presynaptic vesicles with
      multiple antibodies reveals that CHT-positive vesicles carry the vesicular
      acetylcholine transporter (VAChT) and synaptic vesicle markers such as
      synaptophysin and Rab3A and also contain acetylcholine. Depolarization of
      synaptosomes evokes a Ca2+-dependent botulinum neurotoxin C-sensitive increase in
      the Vmax for HC-3-sensitive choline uptake that is accompanied by an increase in
      the density of CHTs in the synaptic plasma membrane. Our study leads to the novel
      hypothesis that CHTs reside on a subpopulation of synaptic vesicles in
      cholinergic terminals that can transit to the plasma membrane in response to
      neuronal activity to couple levels of choline re-uptake to the rate of ACh
      release.

PMID- 14585996
TI  - Replication checkpoint protein Mrc1 is regulated by Rad3 and Tel1 in fission
      yeast.
AB  - Fission yeast Mrc1 (mediator of replication checkpoint 1) is an adaptor
      checkpoint protein required for Rad3-dependent activation of the checkpoint
      kinase Cds1 in response to arrest of replication forks. Here we report studies on
      the regulation of Mrc1 by phosphorylation. Replication arrest induced by
      hydroxyurea (HU) induces Mrc1 phosphorylation that is detected by a change in
      Mrc1 electrophoretic mobility. Phosphorylation is maintained in cds1Delta,
      rad3Delta, and tel1Delta single mutants but eliminated in a rad3Delta tel1Delta
      double mutant. Mrc1 has two clusters of S/TQ motifs that are potential Rad3/Tel1
      phosphorylation sites. Mutation of six S/TQ motifs in these two clusters strongly
      impairs Mrc1 phosphorylation. Two motifs located at S604 and T645 are vital for
      HU resistance. The T645A mutation strongly impairs a Cds1-Mrc1 yeast two-hybrid
      interaction that is dependent on a functional forkhead-associated (FHA) domain in
      Cds1, indicating that phosphorylation of T645 mediates Mrc1's association with
      Cds1. Consistent with this model, the T645 region of Mrc1 effectively substitutes
      for the T11 region of Cds1 that is thought to be phosphorylated by Rad3 and to
      mediate FHA-dependent oligomerization of Cds1. The S/TQ cluster that includes
      S604 is needed for Mrc1's increased association with chromatin in replication
      arrested cells. These data indicate that Rad3 and Tel1 regulate Mrc1 through
      differential phosphorylation to control Cds1.

PMID- 14585998
TI  - Type 8 adenylyl cyclase is targeted to excitatory synapses and required for mossy
      fiber long-term potentiation.
AB  - Mossy fiber/CA3 long-term potentiation (LTP) is hypothesized to depend on cAMP
      signals generated by Ca2+-stimulated adenylyl cyclases AC1 or AC8. AC1 gene knock
      out mice (AC1-/-) show a partial reduction in mossy fiber LTP, suggesting that
      either AC8 activity is also critical for mossy fiber LTP or that there is a
      component of mossy fiber LTP that is independent of CaM-activated adenylyl
      cyclases. To address this issue, mossy fiber LTP was examined in hippocampal
      slices from AC8-/- and AC1-/- x AC8-/- double knock-out mice (DKO). Despite the
      fact that AC8 contributes only a small fraction of the Ca2+-stimulated adenylyl
      cyclase activity in the hippocampus and is less sensitive to Ca2+ than AC1, AC8-/
      mice exhibited mossy fiber LTP defects comparable with AC1-/- and DKO mice.
      Furthermore, short-term plasticity was disrupted in AC8-/- mice but not in AC1-/-
      mice. Because AC1 is not localized at the excitatory synapses in hippocampal
      neurons, we hypothesized that AC8 may be targeted to synapses, in which higher
      synaptic-specific Ca2+ increases occur. Here, we report that AC8 accumulates in
      puncta of dendrites and axons in hippocampal neurons and colocalizes with
      synaptic marker proteins. These data indicate that both synaptic and nonsynaptic
      cAMP signals, generated by different Ca2+-stimulated adenylyl cyclases, are
      required for mossy fiber LTP.

PMID- 14585999
TI  - Hippocampal place cell instability after lesions of the head direction cell
      network.
AB  - The occurrence of cells that encode spatial location (place cells) or head
      direction (HD cells) in the rat limbic system suggests that these cell types are
      important for spatial navigation. We sought to determine whether place fields of
      hippocampal CA1 place cells would be altered in animals receiving lesions of
      brain areas containing HD cells. Rats received bilateral lesions of anterodorsal
      thalamic nuclei (ADN), postsubiculum (PoS), or sham lesions, before place cell
      recording. Although place cells from lesioned animals did not differ from
      controls on many place-field characteristics, such as place-field size and
      infield firing rate, the signal was significantly degraded with respect to
      measures of outfield firing rate, spatial coherence, and information content.
      Surprisingly, place cells from lesioned animals were more likely modulated by the
      directional heading of the animal. Rotation of the landmark cue showed that place
      fields from PoS-lesioned animals were not controlled by the cue and shifted
      unpredictably between sessions. Although fields from ADN-lesioned animals tended
      to have less landmark control than fields from control animals, this impairment
      was mild compared with cells recorded from PoS-lesioned animals. Removal of the
      prominent visual cue also led to instability of place-field representations in
      PoS-lesioned, but not ADN-lesioned, animals. Together, these findings suggest
      that an intact HD system is not necessary for the maintenance of place fields,
      but lesions of brain areas that convey the HD signal can degrade this signal, and
      lesions of the PoS might lead to perceptual or mnemonic deficits, leading to
      place-field instability between sessions.

PMID- 14586000
TI  - Neuronal migration depends on intact peroxisomal function in brain and in
      extraneuronal tissues.
AB  - Functional peroxisome deficiency, as encountered in Zellweger syndrome, causes a
      specific impairment of neuronal migration. Although the molecular mechanisms
      underlying the neuronal migration defect are at present unknown, the excess of
      very long chain fatty acids in brain, a consequence of peroxisomalbeta-oxidation
      deficiency, has often been hypothesized to play a major role. The purpose of the
      present study was to investigate the contribution of peroxisomal dysfunction in
      brain as opposed to peroxisomal dysfunction in extraneuronal tissues to the
      migration defect. Peroxisomes were selectively reconstituted either in brain or
      liver of Pex5 knock-out mice, a model for Zellweger syndrome, by tissue-selective
      overexpression of Pex5p. We found that both rescue strains exhibited a
      significant correction of the neuronal migration defect despite an incomplete
      reconstitution of peroxisomal function in the targeted tissue. Animals with a
      simultaneous rescue of peroxisomes in both tissues displayed a pattern of
      neuronal migration indistinguishable from that of wild-type animals on the basis
      of cresyl violet staining and 5',3'-bromo-2'-deoxyuridine birth-dating analysis.
      These data suggest that peroxisomal metabolism in brain but also in extraneuronal
      tissues affects the normal development of the mouse neocortex. In liver-rescued
      mice, the improvement of the neuronal migration was not accompanied by changes in
      very long chain fatty acid, docosahexaenoic acid, or plasmalogen levels in brain,
      indicating that other metabolic factors can influence the neuronal migration
      process.

PMID- 14586001
TI  - Cerebellar signatures of vestibulo-ocular reflex motor learning.
AB  - The vestibulo-ocular reflex (VOR) comprises an outstanding system to perform
      studies that probe possible cerebellar roles in motor learning. Novel VOR gains
      can be induced (learned) by the wearing of minifying or magnifying lenses, and
      learning requires the presence of the cerebellum. Previously, it was shown that
      Purkinje cells change their head velocity sensitivities with learning and that
      this change was thought to be inappropriate to be causal for the changed
      behavior. We now demonstrate that Purkinje cells also change their eye position,
      eye velocity, and head velocity sensitivities after learning. These combined
      changes at the Purkinje cell level contribute to a net modulation that is
      appropriate to support the new VOR gains. Importantly, the changes in the eye
      position parameter, reported for the first time, suggest the involvement of the
      neuronal integrator pathways in VOR learning. We provide evidence that all of
      these changes are necessary for VOR behavior and can explain learning deficits
      after cerebellar removal.

PMID- 14586002
TI  - Loss of Ca2+/calmodulin kinase kinase beta affects the formation of some, but not
      all, types of hippocampus-dependent long-term memory.
AB  - Long-term memory (LTM) requires activation of the transcription factor cAMP
      responsive element binding protein (CREB). Signaling by the Ca2+/calmodulin (CaM)
      kinase cascade has been implicated in CREB activation and memory consolidation
      processes in the hippocampus. The CaM kinase kinase beta isoforms belong to the
      CaM kinase cascade, and we have generated null mutant mice to investigate the
      role of these kinases in several forms of learning and memory. The null mutants
      were impaired in spatial training-induced CREB activation and spatial memory
      formation. Furthermore, the mutants lacked late, but not early, long-term
      potentiation at the hippocampal CA1 synapse, and they were impaired in LTM, but
      not short-term memory, for the social transmission of food preferences. We
      suggest that the CaM kinase kinasebeta isoforms are required for the formation of
      hippocampal LTM. Surprisingly, however, these kinases were not needed for
      contextual, trace fear, and passive avoidance LTM. Our results demonstrate that
      different signaling processes underlie the formation of these types of
      hippocampal LTM.

PMID- 14586004
TI  - Spontaneous functional viscerosensory regeneration into the adult brainstem.
AB  - The dorsal root entry zone of the vagus nerve (vDREZ) is uniquely characterized
      by peripheral tissue insertions (PTIs) deep to the brainstem surface, consisting
      of Schwann cells and a reticulum of astrocytic processes. Because Schwann cells
      permit peripheral axonal regeneration, the capacity of vagal medullary PTIs to
      allow centripetal regeneration of visceral afferents after vagal dorsal rhizotomy
      in adult rats was investigated. The present work shows that vagal axons
      spontaneously regenerate into appropriate and ectopic brainstem nuclei. They
      accomplish this by first growing along PTIs but then extend along basal laminas
      of medullary blood vessels. Electrically stimulated regenerated vagal afferents
      induced Fos expression (indicating functional connectivity) within appropriate
      but not ectopic nuclei. The unique structure of the vDREZ can thus support
      spontaneous functional regeneration of visceral primary afferent axons into the
      adult CNS.

PMID- 14586003
TI  - Gamma oscillations induced by kainate receptor activation in the entorhinal
      cortex in vitro.
AB  - Gamma frequency (30-80 Hz) oscillations are recordable from human and rodent
      entorhinal cortex. A number of mechanisms used by neuronal networks to generate
      such oscillations in the hippocampus have been characterized. However, it is as
      yet unclear as to whether these mechanisms apply to other anatomically disparate
      brain regions. Here we show that the medial entorhinal cortex (mEC) in isolation
      in vitro generates gamma frequency oscillations in response to kainate receptor
      agonists. Oscillations had the same horizontal and laminar spatiotemporal
      distribution as seen in vivo and in the isolated whole-brain preparation.
      Oscillations occurred in the absence of input from the hippocampal formation and
      did not spread to lateral entorhinal regions. Pharmacological similarities
      existed between oscillations in the hippocampus and mEC in that the latter were
      also sensitive to GABAA receptor blockade, barbiturates, AMPA receptor blockade,
      and reduction in gap junctional conductance. Stellate and pyramidal neuron
      recordings revealed a large GABAergic input consisting of gamma frequency IPSP
      trains. Fast spiking interneurons in the superficial mEC generated action
      potentials at gamma frequencies phase locked to the local field. Stellate cells
      also demonstrated a subthreshold membrane potential oscillation at theta
      frequencies that was temporally correlated with a theta-frequency modulation in
      field gamma power. Disruption in this stellate theta frequency oscillation by the
      hyperpolarisation activated current (Ih) blocker ZD7288 also disrupted theta
      modulation of field gamma frequency oscillations. We propose that similar
      cellular and network mechanisms to those seen in the hippocampus generate and
      modulate persistent gamma oscillations in the entorhinal cortex.

PMID- 14586005
TI  - Enhancement of synchronization in a hybrid neural circuit by spike-timing
      dependent plasticity.
AB  - Synchronization of neural activity is fundamental for many functions of the
      brain. We demonstrate that spike-timing dependent plasticity (STDP) enhances
      synchronization (entrainment) in a hybrid circuit composed of a spike generator,
      a dynamic clamp emulating an excitatory plastic synapse, and a chemically
      isolated neuron from the Aplysia abdominal ganglion. Fixed-phase entrainment of
      the Aplysia neuron to the spike generator is possible for a much wider range of
      frequency ratios and is more precise and more robust with the plastic synapse
      than with a nonplastic synapse of comparable strength. Further analysis in a
      computational model of Hodgkin-Huxley-type neurons reveals the mechanism behind
      this significant enhancement in synchronization. The experimentally observed STDP
      plasticity curve appears to be designed to adjust synaptic strength to a value
      suitable for stable entrainment of the postsynaptic neuron. One functional role
      of STDP might therefore be to facilitate synchronization or entrainment of
      nonidentical neurons.

PMID- 14586006
TI  - Depolarization-induced long-term depression at hippocampal mossy fiber-CA3
      pyramidal neuron synapses.
AB  - Hippocampal CA3 pyramidal neurons receive two types of excitatory afferent
      innervation: mossy fibers (MFs) from granule cells of the dentate gyrus and
      recurrent collateral fibers (CFs) from other CA3 pyramidal neurons. At CF-CA3
      pyramidal neuron synapses, membrane depolarization paired with low (0.33 Hz)
      presynaptic stimulation generated a heterogeneous response that ranged from long
      term potentiation (LTP), long-term depression (LTD), to no alteration of synaptic
      strength. However, the same induction paradigm applied at MF-CA3 pyramidal neuron
      synapses consistently induced LTD. This novel form of LTD was independent of
      NMDARs, mGluRs, cannabinoid receptors, opioid receptors, or coincident synaptic
      activity, but was dependent on postsynaptic Ca2+ elevation through L-type Ca2+
      channels and release from inositol 1,4,5-trisphosphate receptor-sensitive
      intracellular stores. Ca2+ imaging of both proximal and distal CA3 pyramidal
      neuron dendrites demonstrated that the depolarizing induction paradigm
      differentially elevated intracellular Ca2+ levels. L-type Ca2+ channel activation
      was observed only at the most proximal locations where mossy fibers make
      synapses. Depolarization-induced LTD did not occlude the conventional 1 Hz
      induced LTD or vice versa, suggesting independent mechanisms underlie each form
      of plasticity. The paired-pulse ratio and coefficient of variation of synaptic
      transmission were unchanged after LTD induction, suggesting that the expression
      locus of LTD is postsynaptic. Moreover, peak-scaled nonstationary variance
      analysis indicated that depolarization-induced LTD correlated with a reduction in
      postsynaptic AMPA receptor numbers without a change in AMPA receptor conductance.
      Our results suggest that this novel form of LTD is selectively expressed at
      proximal dendritic locations closely associated with L-type Ca2+ channels.

PMID- 14586007
TI  - Nonsteroidal anti-inflammatory drugs and peroxisome proliferator-activated
      receptor-gamma agonists modulate immunostimulated processing of amyloid precursor
      protein through regulation of beta-secretase.
AB  - Long-term treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) reduces
      the risk for Alzheimer's disease (AD). To determine the mechanisms by which
      inflammation affects AD and how NSAIDs protect against it, we stimulated
      neuroblastoma cells stably transfected with amyloid precursor protein (APP) with
      proinflammatory cytokines, which increased the secretion of amyloid-beta and APP
      ectodomain. Addition of ibuprofen, indomethacin, peroxisome proliferator
      activated receptor-gamma (PPARgamma) agonists, or cotransfection with PPARgamma
      cDNA reversed this effect. The inhibitory action of ibuprofen and indomethacin
      was suppressed by PPARgamma antagonists. Finally, we observed that the mRNA
      levels, expression, and enzymatic activity of beta-secretase were increased by
      immunostimulation and normalized by NSAIDs. In conclusion, proinflammatory
      cytokines activate beta-secretase, and NSAIDs inhibit this effect through
      PPARgamma.

PMID- 14586008
TI  - Input organization of multifunctional motion-sensitive neurons in the blowfly.
AB  - Flies rely heavily on visual motion cues for course control. This is mediated by
      a small set of motion-sensitive neurons called lobula plate tangential cells. A
      single class of these, the centrifugal horizontal (CH) neurons, play an important
      role in two pathways: figure-ground discrimination and flow-field selectivity. As
      was recently found, the dendrites of CH cells are electrically coupled with the
      dendritic tree of another class of neurons sensitive to horizontal image motion,
      the horizontal system (HS) cells. However, whether motion information arrives
      independently at both of these cells or is passed from one to the other is not
      known. Here, we examine the ipsilateral input circuitry to HS and CH neurons by
      selective laser ablation of individual interneurons. We find that the response of
      CH neurons to motion presented in front of the ipsilateral eye is entirely
      abolished after ablation of HS cells. In contrast, the motion response of HS
      cells persists after the ablation of CH cells. We conclude that HS cells receive
      direct motion input from local motion elements, whereas CH cells do not; their
      motion response is driven by HS cells. This connection scheme is discussed with
      reference to how the dendritic networks involved in figure-ground detection and
      flow-field selectivity might operate.

PMID- 14586009
TI  - Dynamic interaction of object- and space-based attention in retinotopic visual
      areas.
AB  - We investigated the interaction between object- and space-based attention by
      measuring activity in early visual cortex. After central cueing, when subjects
      directed attention to a spatially defined part of an object, activity in early
      visual areas was enhanced at corresponding retinotopic representations but also
      at representations of other locations covered by the object. Different from the
      assumption of automatic attentional "spreading" within an object, however,
      activity was greater for representations of cued than of uncued locations on the
      same object. These findings support an interaction of object-based spatial
      selection with object-independent spatial mechanisms in directing attention. When
      the target stimulus did not appear at the expected location, we found higher
      activation in areas representing other locations on the same object than
      equidistant locations on other objects. Objects, hence, also guide spatial
      search, and this may account for the behaviorally observed delay in processing
      parts of an unattended object.

PMID- 14586010
TI  - Discrete gene loci regulate neurodegeneration, lymphocyte infiltration, and major
      histocompatibility complex class II expression in the CNS.
AB  - Neurodegeneration and inflammation are fundamental aspects of many neurological
      diseases. A genome-wide scan of the response to ventral root avulsion (VRA) in a
      rat F2 cross discloses specific gene regions that regulate these processes. Two
      gene loci displayed linkage to neurodegeneration and T cell infiltration,
      respectively, and a single locus displayed extreme linkage to VRA-induced major
      histocompatibility complex class II expression on microglia. The demonstration
      that polymorphic genes in different loci control neurodegeneration and CNS
      inflammation has implications for various experimental rodent nervous system
      paradigms and potentially for genetically regulated susceptibility to a variety
      of human CNS diseases.

PMID- 14586011
TI  - Functional genomic analysis of remyelination reveals importance of inflammation
      in oligodendrocyte regeneration.
AB  - Tumor necrosis factor alpha (TNFalpha), a proinflammatory cytokine, was shown
      previously to promote remyelination and oligodendrocyte precursor proliferation
      in a murine model for demyelination and remyelination. We used Affymetrix
      microarrays in this study to identify (1) changes in gene expression that
      accompany demyelination versus remyelination and (2) changes in gene expression
      during the successful remyelination of wild-type mice versus the unsuccessful
      attempts in mice lacking TNFalpha. Alterations in inflammatory genes represented
      the most prominent changes, with major histocompatibility complex (MHC) genes
      dramatically enhanced in microglia and astrocytes during demyelination,
      remyelination, and as a consequence of TNFalpha stimulation. Studies to examine
      the roles of these genes in remyelination were then performed using mice lacking
      specific genes identified by the microarray. Analysis of MHC-II-null mice showed
      delayed remyelination and regeneration of oligodendrocytes, whereas removal of
      MHC-I had little effect. These data point to the induction of MHC-II by TNFalpha
      as an important regulatory event in remyelination and emphasize the active
      inflammatory response in regeneration after pathology in the brain.

PMID- 14586012
TI  - Lesions of nucleus accumbens disrupt learning about aversive outcomes.
AB  - Nucleus accumbens (NAcc) is critical for encoding and using information regarding
      the learned significance of cues predictive of reward. However, its role in
      processing information about cues predictive of aversive outcomes is less well
      studied. Here, we examined the effects of NAcc lesions in an odor-guided
      discrimination task in which rats use odor cues predictive of either appetitive
      or aversive outcomes to guide responding. Rats with sham or neurotoxic lesions of
      NAcc were trained on a series of two-odor discrimination problems. Performance on
      each problem was assessed by monitoring accuracy of choice behavior and by
      measuring latency to respond for fluid reinforcement after odor sampling. After
      acquisition of four problems, rats were trained on serial reversals of the final
      problem. Rats with NAcc lesions exhibited normal choice performance relative to
      controls on both acquisition and reversal of the discrimination problems (indeed,
      lesioned rats exhibited a mild facilitation on the first discrimination problem).
      Despite normal choice performance, however, lesioned rats failed to show normal
      changes in response latency during discrimination learning, particularly on
      trials involving the aversive outcome. These findings are consistent with a
      deficit in processing cue-outcome associations. These results are compared with
      those obtained from studies of basolateral amygdala and orbitofrontal cortex
      lesions in this task and suggest that NAcc integrates the motivational value of
      both appetitive and aversive cues to bias or modulate the vigor of subsequent
      responding.

PMID- 14586013
TI  - Extinction requires new RNA and protein synthesis and the soma of the cell right
      pedal dorsal 1 in Lymnaea stagnalis.
AB  - Lymnaea stagnalis were operantly conditioned to not perform aerial respiratory
      behavior. This learned response was subsequently extinguished. Here, we show that
      spaced extinction training is more effective than massed extinction training, in
      addition to the occurrence of spontaneous recovery. We also find evidence of a
      critical period within the first hour after extinction training in which new RNA
      and protein synthesis must occur for a memory of extinction training to be
      established. The memory for extinction training can also be extended using
      cooling and by preventing aerial respiration from occurring after extinction
      training. In addition, we demonstrate that memory formation of extinction
      training requires the soma of the cell right pedal dorsal 1, a cell that we have
      previously shown to be necessary for long-term memory consolidation and
      reconsolidation. This finding implies that the events that lead to the formation
      of extinction memory occur in the same cell that is responsible for long-term
      memory of operant conditioning. All of these data are consistent with the
      hypothesis that, during extinction, a new associative memory is being formed and
      that this new memory covers up, but does not abolish, the "old" memory.

PMID- 14586014
TI  - Regulation of NMDA receptors by dopamine D4 signaling in prefrontal cortex.
AB  - Increasing evidence has suggested that the interaction between dopaminergic and
      glutamatergic systems in prefrontal cortex (PFC) plays an important role in
      normal mental functions and neuropsychiatric disorders. In this study, we
      examined the regulation of NMDA-type glutamate receptors by the PFC dopamine D4
      receptor (one of the principal targets of antipsychotic drugs). Application of
      the D4 receptor agonist PD168077 caused a reversible decrease of the NMDA
      receptor (NMDAR)-mediated current in acutely isolated and cultured PFC pyramidal
      neurons, an effect that was blocked by selective D4 receptor antagonists.
      Furthermore, application of PD168077 produced a potent reduction of the amplitude
      (but not paired-pulse ratio) of evoked NMDAR EPSCs in PFC slices. The D4
      modulation of NMDA receptors in PFC involved the inhibition of protein kinase A,
      activation of protein phosphatase 1 and the ensuing inhibition of active Ca2+
      calmodulin-dependent kinase II (CaMKII). Moreover, PD168077 reduced the surface
      expression of NMDARs and triggered the internalization of NMDARs in a manner
      dependent on CaMKII activity. These results identify a mechanistic link between
      D4 and NMDA receptors in PFC pyramidal neurons, suggesting that D4 receptors may
      play an important role in modulating synaptic plasticity and thus cognitive and
      emotional processes in PFC circuits.

PMID- 14586015
TI  - Sonic hedgehog and bone morphogenetic protein regulate interneuron development
      from dorsal telencephalic progenitors in vitro.
AB  - Cortical progenitors are competent to produce interneurons, but do not generate
      large numbers of interneurons in vivo under normal circumstances. This could
      reflect the absence of an inductive signal in the environment of the dorsal
      telencephalon and/or the presence of an inhibitory signal. To determine whether
      either or both mechanisms regulate interneuron generation, progenitors in
      dorsomedial and dorsolateral wall explants of mouse telencephalon were marked
      with a retrovirus and cultured under several conditions. When cultured
      separately, progenitors in dorsomedial wall explants produced fewer GABAergic
      interneurons than progenitors in dorsolateral wall explants. When cocultured with
      ventral telencephalic cells, however, dorsomedial wall progenitors produced more
      GABAergic interneurons than in dorsomedial wall explants alone. The inductive
      effect of ventral telencephalon depended on sonic hedgehog (Shh) and could be
      mimicked by exogenous Shh. In contrast, exogenous bone morphogenetic protein 4
      (BMP4) reduced the production of interneurons in dorsolateral wall explants and
      inhibited the induction by exogenous Shh. Moreover, inhibiting BMP signaling in
      dorsomedial wall progenitors with a dominant-negative BMP receptor Ib (dnBMPIb)
      virus increased their production of interneurons, even if Shh was blocked. Shh
      and dnBMPRIb increased proliferation and the generation of interneurons, but FGF2
      did not induce interneurons, although it increased proliferation. This suggests
      that proliferation per se does not control the production of interneurons. Our
      findings suggest that the generation of interneurons by dorsal telencephalic
      progenitors is normally limited by excess levels of BMPs. Shh may promote the
      generation of interneurons by antagonizing BMP, but may not be required directly
      for the generation of interneurons.

PMID- 14586017
TI  - Macaque retina contains an S-cone OFF midget pathway.
AB  - Psychophysical results suggest that the primate visual system is equally
      sensitive to both the onset and offset of short-wavelength light and that these
      responses are carried by separate pathways. However, physiological studies of
      cells in the retina and lateral geniculate nucleus find far fewer OFF-center than
      ON-center cells whose receptive-field centers are driven by short-wavelength
      sensitive (S) cones. To determine whether S cones contact ON and OFF midget
      bipolar cells as well as (ON) "blue-cone bipolar" cells (Mariani, 1984), we
      examined 118 contiguous cone terminals and their bipolar cells in electron
      micrographs of serial sections from macaque foveal retina. Five widely spaced
      cone terminals do not contact ON midget bipolar cells. These five cone terminals
      contact the dendrites of "blue-cone bipolar" cells instead, showing that they are
      the terminals of S cones. These S-cone terminals are smaller and contain more
      synaptic ribbons than other terminals. Like neighboring cones, each S cone
      contacts its own OFF midget bipolar cell via triad-associated (flat) synaptic
      contacts. Moreover, each S-cone OFF midget bipolar cell has a synaptic terminal
      in the outer half of the inner plexiform layer, where it contacts an OFF midget
      ganglion cell.

PMID- 14586016
TI  - R-cadherin is a Pax6-regulated, growth-promoting cue for pioneer axons.
AB  - The transcription factor Pax6 has been implicated in two processes that may be
      related in brain development: establishment of regional cell adhesion properties
      and axon guidance. In Pax6 mutant mouse embryos, forebrain pioneer axons make
      pathfinding errors. These errors occur in a region of the ventral thalamus in
      which the expression of the cell adhesion molecule R-cadherin (Cdh4) is lost in
      Pax6 mutants. In vitro, an R-cadherin substrate promoted pioneer axon outgrowth.
      Furthermore, pioneer axon outgrowth was rescued in vivo by selective replacement
      of R-cadherin by electroporation into cultured Pax6 mutant embryos. Thus, these
      studies implicate Pax6 as an early brain patterning gene that establishes
      regional adhesive codes to guide pioneer axons.

PMID- 14586018
TI  - Different mechanisms promote astrocyte Ca2+ waves and spreading depression in the
      mouse neocortex.
AB  - Cortical spreading depression (CSD) is thought to play an important role in
      different pathological conditions of the human brain. Here we investigated the
      interaction between CSD and Ca2+ waves within the astrocyte population in slices
      from mouse neocortex (postnatal days 10-14). After local KCl ejection as a
      trigger for CSD, we recorded the propagation of Ca2+ increases within a large
      population of identified astrocytes in synchrony with CSD measured as intrinsic
      optical signal (IOS) or negative DC-potential shift. The two events spread with
      39.2 +/- 3.3 mum/sec until the IOS and negative DC-potential shift decayed after
      approximately 1 mm. However, the astrocyte Ca2+ wave continued to propagate for
      up to another 500 microm but with a reduced speed of 18.3 +/- 2.5 microm/sec that
      is also typical for glial Ca2+ waves in white matter or culture. While blocking
      CSD using MK-801 (40 microm), an NMDA-receptor antagonist, the astrocyte Ca2+
      wave persisted with a reduced speed (13.2 +/- 1.5 microm/sec). The specific gap
      junction blocker carbenoxolon (100 microm) did not prevent CSD but decelerated
      the speed (2.9 +/- 0.9 microm/sec) of the astrocyte Ca2+ wave in the periphery of
      CSD. We also found that interfering with intracellular astrocytic Ca2+ signaling
      by depletion of internal Ca2+ stores does not affect the spread of the IOS. We
      conclude that CSD determines the velocity of an accompanying astrocytic Ca2+
      response, but the astrocyte Ca2+ wave penetrates a larger territory and by this
      represents a self-reliant phenomenon with a different mechanism of propagation.

PMID- 14586019
TI  - Time-dependent reorganization of the brain components underlying memory retention
      in trace eyeblink conditioning.
AB  - Many studies have confirmed the time-limited involvement of the hippocampus in
      mnemonic processes and suggested that there is reorganization of the responsible
      brain circuitry during memory consolidation. To clarify such reorganization, we
      chose trace classical eyeblink conditioning, in which hippocampal ablation
      produces temporally graded retrograde amnesia. Here, we extended the temporal
      characterization of retrograde amnesia to other regions that are involved in
      acquisition during this task: the medial prefrontal cortex (mPFC) and the
      cerebellum. At a various time interval after establishing the trace conditioned
      response (CR), rats received an aspiration of one of the three regions. After
      recovery, the animals were tested for their CR retention. When ablated 1 d after
      the learning, both the hippocampal lesion and the cerebellar lesion group of rats
      exhibited a severe impairment in retention of the CR, whereas the mPFC lesion
      group showed only a slight decline. With an increase in interval between the
      lesion and the learning, the effect of the hippocampal lesion diminished and that
      of the mPFC lesion increased. When ablated 4 weeks after the learning, the
      hippocampal lesion group exhibited as robust CRs as its corresponding control
      group. In contrast, the mPFC lesion and the cerebellar lesion groups failed to
      retain the CRs. These results indicate that the hippocampus and the cerebellum,
      but only marginally the mPFC, constitute a brain circuitry that mediates recently
      acquired memory. As time elapses, the circuitry is reorganized to use mainly the
      mPFC and the cerebellum, but not the hippocampus, for remotely acquired memory.

PMID- 14586020
TI  - Targeted mutation of a Drosophila odor receptor defines receptor requirement in a
      novel class of sensillum.
AB  - In vertebrates, individual olfactory neurons are thought to express a single
      odorant receptor (Or) gene, but it is not clear that all odor-evoked activity in
      each neuron is exclusively dependent on an individual odorant receptor. In
      Drosophila, little is known about what receptors impart odor sensitivity to
      particular olfactory neurons. Here, we demonstrate the use of gene targeting to
      produce a null mutant of the putative odorant receptor Or43b and find that the
      mutant is defective for odor-evoked activity in ab8A neurons, a single functional
      class of olfactory neurons in Drosophila. ab8A neurons lacking Or43b are still
      present in the mutants and display spontaneous activity but are insensitive to
      odor stimulation. Therefore, Or43b is required for odor responsiveness in these
      olfactory neurons in vivo. Or83b, a receptor expressed in a large fraction of
      olfactory neurons including Or43b neurons, does not confer odor responsiveness in
      the absence of Or43b. Olfactory behavior elicited by odorants that activate the
      ab8A neurons is indistinguishable between Or43b mutants and controls,
      demonstrating a surprising degree of functional redundancy among the limited odor
      receptor repertoire in this species. These studies demonstrate that a reverse
      genetic approach can be used to correlate specific olfactory receptors with odor
      specificity of functional classes of olfactory neurons.

PMID- 14586021
TI  - Correlated coding of motivation and outcome of decision by dopamine neurons.
AB  - We recorded the activity of midbrain dopamine neurons in an instrumental
      conditioning task in which monkeys made a series of behavioral decisions on the
      basis of distinct reward expectations. Dopamine neurons responded to the first
      visual cue that appeared in each trial [conditioned stimulus (CS)] through which
      monkeys initiated trial for decision while expecting trial-specific reward
      probability and volume. The magnitude of neuronal responses to the CS was
      approximately proportional to reward expectations but with considerable
      discrepancy. In contrast, CS responses appear to represent motivational
      properties, because their magnitude at trials with identical reward expectation
      had significant negative correlation with reaction times of the animal after the
      CS. Dopamine neurons also responded to reinforcers that occurred after behavioral
      decisions, and the responses precisely encoded positive and negative reward
      expectation errors (REEs). The gain of coding REEs by spike frequency increased
      during learning act-outcome contingencies through a few months of task training,
      whereas coding of motivational properties remained consistent during the
      learning. We found that the magnitude of CS responses was positively correlated
      with that of reinforcers, suggesting a modulation of the effectiveness of REEs as
      a teaching signal by motivation. For instance, rate of learning could be faster
      when animals are motivated, whereas it could be slower when less motivated, even
      at identical REEs. Therefore, the dual correlated coding of motivation and REEs
      suggested the involvement of the dopamine system, both in reinforcement in more
      elaborate ways than currently proposed and in motivational function in reward
      based decision-making and learning.

PMID- 14586022
TI  - The spatial order of horizontal cells is not affected by massive alterations in
      the organization of other retinal cells.
AB  - To test whether retinal mosaics develop through interactions that are restricted
      primarily to the mosaic cells, we studied the horizontal cell mosaic in mutant
      mice (rd/rd and rd/bcl2) displaying severe retinal abnormalities. These mutants
      show that the horizontal cell mosaic develops normally even if these cells lack
      part of their synaptic input, have anomalous morphologies, eventually decrease in
      number, and reside in an abnormally packed retinal layer. These data strongly
      support a developmental design in which the final position of each cell in a
      retinal mosaic is controlled by interactions between homotypic cells and is
      independent of other cell types. The present analysis is also an investigation of
      the effects of photoreceptor degeneration on the horizontal cells in an
      established animal model of retinitis pigmentosa, the rd/rd mouse. We find that
      the organization of the horizontal cell mosaic resists photoreceptor degeneration
      and, furthermore, that bcl2 overexpression prevents the partial loss of
      horizontal cells secondary to photoreceptor loss. Secondary degeneration hampers
      attempts to restore retinal function by transplanting photoreceptors or promoting
      their survival. The anti-apoptotic gene bcl2 appears to be a promising tool to
      rescue inner retinal neurons, increasing the probability that photoreceptor
      rescue or substitution may be beneficial to subjects suffering from retinal
      degenerative diseases.

PMID- 14586023
TI  - Spontaneous and evoked activity of substantia nigra pars reticulata neurons
      during high-frequency stimulation of the subthalamic nucleus.
AB  - The subthalamic nucleus (STN), a major component of the basal ganglia, exerts an
      excitatory influence on the output structures of this system i.e., the substantia
      nigra pars reticulata (SNR) and the internal segment of the globus pallidus. High
      frequency stimulation of the STN is a method currently used to treat parkinsonian
      symptoms. The aim of the present study was to analyze the effects of STN high
      frequency stimulation on the activity of SNR neurons and to investigate its
      impact on the transfer of information between the cerebral cortex and the SNR.
      During STN high-frequency stimulation, the activity of SNR cells was decreased at
      low-intensity stimulation, whereas it was increased at a higher intensity. The
      decrease in the discharge of SNR cells likely results from the activation of a
      GABAergic transmission in the SNR because this effect was blocked by local
      application of bicuculline. The increased activity likely results from the
      activation of the glutamatergic subthalamonigral projection because the latency
      of the evoked excitations was consistent with the conduction time of the
      subthalamonigral neurons. Finally, during STN high-frequency stimulation, the
      transmission of cortical information along the direct trans-striatal pathway was
      preserved, whereas the functionality of the trans-subthalamic pathways was partly
      preserved or completely blocked depending on the stimulation intensity. The
      present data indicate that STN high-frequency stimulation influences the activity
      of SNR cells through activation of their excitatory and inhibitory synaptic
      afferent pathways as well as antidromic activation of the projection neurons.

PMID- 14586024
TI  - Psychostimulant-induced plasticity of intrinsic neuronal excitability in ventral
      subiculum.
AB  - Psychostimulant drugs such as amphetamine are prescribed to increase vigilance,
      suppress appetite, and treat attention disorders, but they powerfully activate
      the dopamine system and have serious abuse potential. Repeated psychostimulant
      exposure induces neuronal plasticity within the mesolimbic dopamine system. Here
      we present evidence that repeated amphetamine exposure results in a suppression
      of intrinsic neuronal excitability in the ventral subiculum, a hippocampal region
      that activates dopamine neurotransmission. We used patch-clamp recordings from
      brain slices obtained at different times after withdrawal from repeated
      amphetamine exposure to determine the long-term effects of amphetamine on
      subicular excitability. Using several postsynaptic indices of sodium channel
      function, our results show that excitability is decreased for days, but not
      weeks, after repeated amphetamine exposure. The resulting increase in action
      potential threshold and decrease in postsynaptic amplification of excitatory
      synaptic input provide the first direct evidence that psychostimulants induce
      plasticity of hippocampal output and suggest one mechanism by which drug
      withdrawal may influence limbic dopamine-dependent learning and memory.

PMID- 14586025
TI  - Role of the G-protein subunit alpha-gustducin in taste cell responses to bitter
      stimuli.
AB  - Many bitter stimuli are believed to bind to specific G-protein-coupled membrane
      receptors on taste cells. Despite the compelling evidence for its pivotal role in
      bitter taste sensation, a direct involvement of the G-protein subunit alpha
      gustducin in bitter taste transduction in taste cells has not been demonstrated
      in situ at the cellular level. We recorded activation of taste cells by bitter
      stimuli using Ca2+ imaging in lingual slices and examined alpha-gustducin
      immunoreactivity in the same cells. In mice vallate papillae, many, but not all,
      bitter-responsive cells expressed alpha-gustducin. In agreement with this
      correlation, the incidence of cells responding to bitter stimuli was reduced by
      70% in mutant mice lacking alpha-gustducin. Nevertheless, some taste cells
      lacking alpha-gustducin responded to bitter stimuli, suggesting that other G
      protein alpha subunits are involved. We found that the G-protein alpha subunit
      Galpha(i2) is present in most bitter-responsive cells and thus may also play a
      role in bitter taste transduction. The reduced behavioral sensitivity to bitter
      stimuli in alpha-gustducin knock-out mice thus appears to be the consequence of a
      reduced number of bitter-activated taste cells, as well as reduced sensitivity.

PMID- 14586026
TI  - Inhibition of SRC family kinases and non-classical protein kinases C induce a
      reeler-like malformation of cortical plate development.
AB  - During development, most cortical neurons migrate to the cortical plate (CP)
      radially. CP development is abnormal in reeler and other mutant mice with
      defective Reelin signaling. Reelin is secreted by Cajal-Retzius cells and binds
      to the very low density lipoprotein receptor and apolipoprotein E receptor type 2
      receptors on the surface of CP cells, inducing tyrosine phosphorylation of the
      intracellular Dab1 adapter. As with Reelin receptors, the identification of
      Reelin signaling partners is hampered by genetic redundancy. Using a new in vitro
      embryonic slice culture system, we demonstrate that chemical inhibitors of Src
      family kinases and Abl, but not inhibitors of Abl alone, generate a reeler-like
      malformation and that inhibitors of protein kinases C induce a malformation of
      cortical development that is also reminiscent of reeler. Our observations
      demonstrate a key role for these enzymes in radial migration to the cortical
      plate, possibly via interference with Reelin signaling.

PMID- 14586027
TI  - Visuomotor sensitivity to visual information about surface orientation.
AB  - We measured human visuomotor sensitivity to visual information about three
      dimensional surface orientation by analyzing movements made to place an object on
      a slanted surface. We applied linear discriminant analysis to the kinematics of
      subjects' movements to surfaces with differing slants (angle away form the fronto
      parallel) to derive visuomotor d's for discriminating surfaces differing in slant
      by 5 degrees. Subjects' visuomotor sensitivity to information about surface
      orientation was very high, with discrimination "thresholds" ranging from 2 to 3
      degrees. In a first experiment, we found that subjects performed only slightly
      better using binocular cues alone than monocular texture cues and that they
      showed only weak evidence for combining the cues when both were available,
      suggesting that monocular cues can be just as effective in guiding motor behavior
      in depth as binocular cues. In a second experiment, we measured subjects'
      perceptual discrimination and visuomotor thresholds in equivalent stimulus
      conditions to decompose visuomotor sensitivity into perceptual and motor
      components. Subjects' visuomotor thresholds were found to be slightly greater
      than their perceptual thresholds for a range of memory delays, from 1 to 3 s. The
      data were consistent with a model in which perceptual noise increases with
      increasing delay between stimulus presentation and movement initiation, but motor
      noise remains constant. This result suggests that visuomotor and perceptual
      systems rely on the same visual estimates of surface slant for memory delays
      ranging from 1 to 3 s.

PMID- 14586028
TI  - Conjugate adaptation of saccadic gain in non-human primates with strabismus.
AB  - In this study, we have used the double-step paradigm to test saccadic gain
      adaptation during monocular viewing in one normal monkey, two monkeys with
      exotropia, and one monkey with esotropia. In this paradigm, the target for the
      saccade is displaced during the saccade, resulting in a consistent visual error.
      Studies in normal humans and monkeys have shown that the brain responds to this
      consistent visual error by gradually changing saccade gain. Using this technique,
      we were able to elicit adaptation in both the viewing eye and the nonviewing eye
      in the normal monkey and in monkeys with strabismus. The rate of adaptation was
      not significantly different in the viewing and nonviewing eyes in the normal and
      strabismic monkeys. The magnitude of adaptation as calculated by a percentage
      change in gain was also not significantly different in the viewing and the
      nonviewing eyes in the normal and strabismic monkeys. Our data show that animals
      with strabismus retain the ability to elicit a conjugate adaptation of saccades
      using this mechanism. We also suggest that the double-step paradigm elicits a
      conjugate adaptation of saccades whether the animal is viewing monocularly (our
      studies) or binocularly (data published in literature).

PMID- 14586029
TI  - Prefrontal neuronal activity encodes spatial target representations sequentially
      updated after nonspatial target-shift cues.
AB  - We examined prefrontal neuronal activity while monkeys performed a sequential
      target-shift task, in which, after a positional cue indicated the initial saccade
      target among 8 peripheral positions, the monkeys were required to internally
      shift the target by one position on every flash of a target-shift cue. The target
      shift cue appeared in the center 0 to 3 times within a single trial and was
      always the same in shape, size, and color. We found selective neuronal activity
      related to the target position: when the target-shift cue implied the target
      shift to particular peripheral positions, neurons exhibited early-dominant and
      late-dominant activity during the following delay period. The early-dominant
      target-selective activity emerged early in the delay just after the presentation
      of the target-shift cue, whereas the late-dominant activity gradually built up
      toward the end of the delay. Because the target-shift cue was not related to any
      specific target location, the early-dominant target-selective activity could not
      be a mere visual response to the target-shift cue. We suggest that the early
      dominant activity reflects the transitory representation for the saccade target
      that was triggered by the nonspatial target-shift cue, whereas the late-dominant
      activity reflects the target representation in the spatial working memory or the
      preparatory set for the possible impending saccade, being repeatedly updated
      during sequential target shifts.

PMID- 14586030
TI  - Corticothalamic inhibition in the thalamic reticular nucleus.
AB  - Mutual inhibition between the GABAergic cells of the thalamic reticular nucleus
      (RTN) is important in regulating oscillations in the thalamocortical network,
      promoting those in the spindle range of frequencies over those at lower
      frequencies. Excitatory inputs to the RTN from the cerebral cortex are
      numerically large and particularly powerful in inducing spindles. However, the
      extent to which corticothalamic influences can engage the inhibitory network of
      the RTN has not been fully explored. Focal electrical stimulation of layer VI in
      the barrel cortex of the mouse thalamocortical slice in vitro resulted in
      prominent di- or polysynaptic inhibitory postsynaptic currents (IPSCs) in RTN
      cells under the experimental conditions used. The majority of cortically induced
      responses consisted of mixed PSCs in which the inhibitory component predominated
      or of large IPSCs alone, implying inhibition of neighboring cells by other,
      cortically excited RTN cells. Within the mixed PSCs, fixed and variable latency
      components could commonly be identified. IPSCs could be blocked by application of
      ionotropic glutamate receptor antagonists or of GABA(A) receptor antagonists,
      also indicating their dependence on corticothalamic excitation triggering
      disynaptic or polysynaptic inhibition. Spontaneous GABA(A) receptor-dependent
      IPSCs were routinely observed in the RTN and, taken together with the results of
      cortical stimulation, indicate the existence of a substantial network of
      intrareticular inhibitory connections that can be effectively recruited by the
      corticothalamic system. These results suggest activation of cortical excitatory
      inputs triggers the propagation of inhibitory currents within the RTN and support
      the view that activation of the RTN from the somatosensory cortex, although
      focused by the topography of the corticothalamic projection, is capable of
      disynaptically engaging the whole inhibitory network of the RTN, by local and
      probably by reentrant GABA(A) receptor-based synapses, thus spreading the
      corticothalamic influence throughout the RTN.

PMID- 14586031
TI  - Effects of prolactin on ionic membrane conductances in the human malignant
      astrocytoma cell line U87-MG.
AB  - Prolactin (PRL) is involved in numerous biological processes in peripheral
      tissues and the brain. Although numerous studies have been conducted to elucidate
      the signal transduction pathways associated with the PRL receptor, very few have
      examined the role of ion conductances in PRL actions. We used the patch-clamp
      technique in "whole cell" configuration and microspectrofluorimetry to
      investigate the effects of PRL on membrane ion conductances in the U87-MG human
      malignant astrocytoma cell line, which naturally expresses the PRL receptor. We
      found that a physiological concentration (4 nM) of PRL exerted a biphasic action
      on membrane conductances. First, PRL activated a Ca(2+)-dependent K(+) current
      that was sensitive to CTX and TEA. This current depended on PRL-induced Ca(2+)
      mobilization, through a JAK2-dependent pathway from a thapsigargin- and 2-APB
      sensitive Ca(2+) pool. Second, PRL also activated an inwardly directed current,
      mainly due to the stimulation of calcium influx via nickel- and 2-APB-sensitive
      calcium channels. Both phases resulted in membrane hyperpolarizations, mainly
      through the activation of Ca(2+)-dependent K(+) channels. As shown by combined
      experiments (electrophysiology and microspectrofluorimetry), the PRL-induced
      Ca(2+) influx increased with cell membrane hyperpolarization and conversely
      decreased with cell membrane depolarization. Thus PRL-induced membrane
      hyperpolarizations facilitated Ca(2+) influx through voltage-independent Ca(2+)
      channels. Finally, PRL also activated a DIDS-sensitive Cl(-) current, which may
      participate in the PRL-induced hyperpolarization. These PRL-induced conductance
      activations are probably related to the PRL proliferative effect we have already
      described in U87-MG cells.

PMID- 14586032
TI  - Roles of CaMKII, PKA, and PKC in the induction and maintenance of LTP of C-fiber
      evoked field potentials in rat spinal dorsal horn.
AB  - Long-term potentiation (LTP) of C-fiber-evoked field potentials in spinal dorsal
      horn may be relevant to hyperalgesia, an increased response to noxious
      stimulation. The mechanism underlying this form of synaptic plasticity is,
      however, still unclear. Considerable evidence has shown that calcium/calmodulin
      dependent protein kinase II (CaMKII), protein kinase A (PKA), and protein kinase
      C (PKC) are important for LTP in hippocampus. In this study, the roles of these
      three protein kinases in the induction and maintenance of LTP of C-fiber-evoked
      field potentials were evaluated by application of specific inhibitors of CaMKII
      (KN-93 and AIP), PKA (Rp-CPT-cAMPS), and PKC (chelerythrine and Go 6983) at the
      recording segments before and after LTP induction in urethane-anesthetized
      Sprague-Dawley rats. We found both KN-93 and AIP, when applied at 30 min prior to
      tetanic stimulation, completely blocked LTP induction. At 30 min after LTP
      induction, KN-93 and AIP reversed LTP completely, and at 60 min after LTP
      induction, they depressed spinal LTP in most rats tested. Three hours after LTP
      induction, however, KN-93 or AIP did not affect the spinal LTP. Rp-CPT-cAMPS,
      chelerythrine, and Go 6983 blocked the spinal LTP when applied at 30 min before
      tetanic stimulation and reversed LTP completely at 15 min after LTP induction. In
      contrast, at 30 min after LTP induction, the drugs never affected the spinal LTP.
      These results suggest that activation of CaMKII, PKA, and PKC may be crucial for
      the induction and the early-phase but not for the late-phase maintenance of the
      spinal LTP.

PMID- 14586033
TI  - Quantification of the factors that influence discharge correlation in model motor
      neurons.
AB  - The purpose of this study was to quantify the influence of intrinsic properties,
      active dendritic conductances, and background excitation and inhibition on
      measures of discharge correlation in the time and frequency domains with known
      levels and patterns of common synaptic input. The study involved a computer
      simulation of a population of neurons with a range of input resistances (0.54-3.7
      MOmega) and surface areas (407,000-712,000 microm(2)). The neurons were simulated
      with no, moderate, or high levels of active dendritic conductances and were
      activated with either excitatory input only or excitatory and inhibitory inputs.
      The patterns of common input, either branched common input or common modulation,
      were tested with 0, 30, 60, and 90% common input. The results confirm previous
      findings of an exponential relation between the level of common input and indexes
      of synchronization; only when the common input comprised >/=60% of the total
      excitatory input was there a significant effect on discharge correlation.
      Synchronization was greatest in models that had passive dendrites. Active
      dendritic conductances caused the discharge rate of the neuron to saturate and
      decreased motor-unit synchronization. However, the addition of 10% background
      inhibitory input increased synchronization in these models. In contrast, common
      rhythmic modulation of inputs at 24 Hz usually decreased synchronization.
      Significant coherence at the modulated frequency occurred in the commonly
      modulated neurons when >/=60% of the inputs were modulated. Furthermore, active
      dendritic conductances decreased coherence. Branched common input caused high
      levels of coherence across a broad spectrum and when combined with active
      dendritic conductances caused significant frequency peaks in the 30- to 50-Hz
      band. In conclusion, the level of inhibitory input and active dendritic
      conductances interact with the amount of common input to determine time- and
      frequency-domain discharge correlation.

PMID- 14586034
TI  - Two distinct regions of secondary somatosensory cortex in the rat: topographical
      organization and multisensory responses.
AB  - In rodents, as in other species, regions of secondary somatosensory cortex (SII)
      may be distinguished from primary cortex (SI) both anatomically and
      electrophysiologically. However, the number of rodent SII subregions, their
      somatotopic organization, and their function are poorly understood. The presence
      of multisensory responsive neurons in some areas of SII suggests that one of its
      roles may be in the integration of somatosensory information with information
      from other sensory modalities. In this study, we used auditory, somatosensory, or
      combined auditory/somatosensory stimuli, and high-resolution epipial-evoked
      potential maps of rat SII to identify the number of spatially discrete
      subregions, estimate their somatotopic organization, and delineate regions with
      multisensory response properties. Maps revealed two distinct subregions within
      SII, one rostral and the other caudal, which were situated lateral to the
      posteromedial barrel subfield. Distinct somatotopies were evident at both SII
      loci, and analysis of evoked responses within both areas indicated multisensory
      interactions. These data are consistent with the presence of classically defined
      rostral SII regions and provide functional evidence for a lesser known, but
      distinct, caudal SII area. Furthermore, evidence for multisensory interactions
      within SII suggests that both secondary areas may process features specifically
      associated with multisensory integration in parallel with unimodal processing in
      primary areas.

PMID- 14586035
TI  - Sensorimotor integration in the precentral gyrus: polysensory neurons and
      defensive movements.
AB  - The precentral gyrus of monkeys contains a polysensory zone in which the neurons
      respond to tactile, visual, and sometimes auditory stimuli. The tactile receptive
      fields of the polysensory neurons are usually on the face, arms, or upper torso,
      and the visual and auditory receptive fields are usually confined to the space
      near the tactile receptive fields, within about 30 cm of the body. Electrical
      stimulation of this polysensory zone, even in anesthetized animals, evokes a
      specific set of movements. The movements resemble those typically used to defend
      the body from objects that are near, approaching, or touching the skin. In the
      present study, to determine whether the stimulation-evoked movements represent a
      normal set of defensive movements, we tested whether they include a distinctive,
      nonsaccadic, centering movement of the eyes that occurs during defensive
      reactions. We report that this centering movement of the eyes is evoked by
      stimulation of sites in the polysensory zone. We also recorded the activity of
      neurons in the polysensory zone while the monkey made defensive reactions to an
      air puff on the face. The neurons became active during the defensive movement,
      and the magnitude of this activity was correlated with the magnitude of the
      defensive reaction. These results support the hypothesis that the polysensory
      zone in the precentral gyrus contributes to the control of defensive movements.
      More generally, the results support the view that the precentral gyrus can
      control movement at the level of complex sensorimotor tasks.

PMID- 14586036
TI  - So inhaled steroids slow the rate of decline of FEV1 in patients with COPD after
      all?

PMID- 14586037
TI  - Lung biopsy guidelines--for the obedience of fools and guidance of wise men.

PMID- 14586038
TI  - Inpatient management of acute COPD: a cause for concern?

PMID- 14586040
TI  - Spotting latent infection: the path to better tuberculosis control.

PMID- 14586041
TI  - Severe acute respiratory syndrome (SARS).

PMID- 14586043
TI  - Inhaled corticosteroids reduce the progression of airflow limitation in chronic
      obstructive pulmonary disease: a meta-analysis.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a syndrome of chronic
      progressive airflow limitation which occurs as a result of chronic inflammation
      of the airways and lung parenchyma. However, the role of inhaled corticosteroids
      in the treatment of COPD is controversial. We hypothesised that inhaled
      corticosteroids reduce the progression of airflow limitation in COPD. METHODS: A
      comprehensive literature search was conducted and data were analysed using random
      effects methodology. The effect of inhaled steroids on annual change in forced
      expiratory volume in 1 second (FEV1) was determined for all trials, for trials
      with high dose treatment regimens, and for trials in subjects with moderate to
      severe airflow limitation. RESULTS: Data from eight controlled clinical trials of
      > or =2 years were included (n=3715 subjects). Meta-analysis of all study data
      revealed that inhaled corticosteroids reduce the rate of FEV1 decline by 7.7
      ml/year (95% confidence interval (CI) 1.3 to 14.2, p=0.02). Meta-analysis of
      studies with high dose regimens revealed a greater effect of 9.9 ml/year (95% CI
      2.3 to 17.5, p=0.01) compared with the meta-analysis of all studies. CONCLUSIONS:
      Inhaled corticosteroid treatment for > or =2 years slows the rate of lung
      function decline in COPD. The effect observed with high dose regimens is greater
      than that with all regimens combined. These data suggest a potential role for
      inhaled corticosteroids in modifying the long term natural history of COPD.

PMID- 14586044
TI  - Inhibition by red wine extract, resveratrol, of cytokine release by alveolar
      macrophages in COPD.
AB  - BACKGROUND: The pathophysiology of chronic obstructive pulmonary disease (COPD)
      features pulmonary inflammation with a predominant alveolar macrophage
      involvement. Bronchoalveolar macrophages from patients with COPD release
      increased amounts of inflammatory cytokines in vitro, an effect that is not
      inhibited by the glucocorticosteroid dexamethasone. Resveratrol (3,5,4'
      trihydroxystilbene) is a component of red wine extract that has anti-inflammatory
      and antioxidant properties. A study was undertaken to determine whether or not
      resveratrol would inhibit cytokine release in vitro by alveolar macrophages from
      patients with COPD. METHODS: Alveolar macrophages were isolated from
      bronchoalveolar lavage (BAL) fluid from cigarette smokers and from patients with
      COPD (n=15 per group). The macrophages were stimulated with either interleukin
      (IL)-1beta or cigarette smoke media (CSM) to release IL-8 and granulocyte
      macrophage-colony stimulating factor (GM-CSF). The effect of resveratrol was
      examined on both basal and stimulated cytokine release. RESULTS: Resveratrol
      inhibited basal release of IL-8 in smokers and patients with COPD by 94% and 88%
      respectively, and inhibited GM-CSF release by 79% and 76% respectively.
      Resveratrol also inhibited stimulated cytokine release. Resveratrol reduced IL
      1beta stimulated IL-8 and GM-CSF release in both smokers and COPD patients to
      below basal levels. In addition, resveratrol inhibited CSM stimulated IL-8
      release by 61% and 51% respectively in smokers and COPD patients, and inhibited
      GM-CSF release by 49% for both subject groups. CONCLUSIONS: Resveratrol inhibits
      inflammatory cytokine release from alveolar macrophages in COPD. Resveratrol or
      similar compounds may be effective pharmacotherapy for macrophage pathophysiology
      in COPD.

PMID- 14586042
TI  - Guidelines for radiologically guided lung biopsy.

PMID- 14586045
TI  - Evidence for a link between mortality in acute COPD and hospital type and
      resources.
AB  - BACKGROUND: The 1997 BTS/RCP national audit of acute care of chronic obstructive
      pulmonary disease (COPD) found wide variations in mortality between hospitals
      which were only partially explained by known audit indicators of outcome. It was
      hypothesised that some of the unexplained variation may result from differences
      in hospital type, organisation and resources. This pilot study examined the
      hypothesis as a factor to be included in a future national audit programme.
      METHODS: Thirty hospitals in England and Wales were randomly selected by
      geographical region and hospital type (teaching, large district general hospital
      (DGH), small DGH). Data on process and outcome of care (death and length of stay)
      were collected retrospectively at 90 days on all prospectively identified COPD
      admissions over an 8 week period. Each centre completed a questionnaire relating
      to organisation and resources available for the care of COPD patients. RESULTS:
      Eleven teaching hospitals, nine large DGHs, and 10 small DGHs provided data on
      1274 cases. Mortality was high (14%) with wide variation between centres (IQR 9
      19%). Small DGHs had a higher mortality (17.5%) than teaching hospitals (11.9%)
      and large DGHs (11.2%). When corrected for confounding factors, an excess of
      deaths in small DGHs was still observed (OR 1.56 (CI 1.04 to 2.35)) v teaching
      hospitals. Analysis of resource and organisational factors suggested higher
      mortality was associated with fewer doctors (OR 1.5) and with fewer patients
      being under the care of a specialist physician (OR 1.8). Small DGHs had fewest
      resources. CONCLUSION: Significant differences in mortality may exist between
      hospital types. The findings justify further study in a proposed national audit.

PMID- 14586047
TI  - Asthma symptoms in women employed in domestic cleaning: a community based study.
AB  - BACKGROUND: Epidemiological studies have shown an association between cleaning
      work and asthma, but the risk factors are uncertain. The aim of this study was to
      assess the risk of asthma in women employed in domestic cleaning. METHODS: A
      cross sectional study was conducted in 4521 women aged 30 to 65 years.
      Information on respiratory symptoms and cleaning work history was obtained using
      a postal questionnaire with telephone follow up. Asthma was defined as reported
      symptoms in the last year or current use of drugs to treat asthma. Odds ratios
      (OR) with 95% confidence intervals (CI) for asthma in different cleaning groups
      were estimated using adjusted unconditional logistic regression models. RESULTS:
      593 women (13%) were currently employed in domestic cleaning work. Asthma was
      more prevalent in this group than in women who had never worked in cleaning (OR
      1.46 (95% CI, 1.10 to 1.92)). Former domestic cleaning work was reported by 1170
      women (26%), and was strongly associated with asthma (OR 2.09 (1.70 to 2.57)).
      Current and former non-domestic cleaning work was not significantly associated
      with asthma. Consistent results were obtained for other respiratory symptoms.
      Twenty five per cent of the asthma cases in the study population were
      attributable to domestic cleaning work. CONCLUSIONS: Employment in domestic
      cleaning may induce or aggravate asthma. This study suggests that domestic
      cleaning work has an important public health impact, probably involving not only
      professional cleaners but also people undertaking cleaning tasks at home.

PMID- 14586048
TI  - Effects of volatile organic compounds, damp, and other environmental exposures in
      the home on wheezing illness in children.
AB  - BACKGROUND: The effects of indoor exposure to volatile organic compounds (VOCs),
      including formaldehyde, on respiratory health are not clearly understood. The aim
      of this study was to determine the independent effects of VOCs and other common
      environmental exposures in the home on the risk and severity of persistent
      wheezing illness in children. METHODS: Total volatile organic compounds,
      formaldehyde, nitrogen dioxide, damp (on a four category scale of % wood moisture
      equivalent), and environmental tobacco smoke (from salivary cotinine) were
      measured objectively in the homes of 193 children with persistent wheezing
      illness and 223 controls aged 9-11 years in Nottingham, UK. RESULTS: The risk of
      wheezing illness was significantly increased only in relation to damp (odds ratio
      (OR) per increasing category=1.32 (95% confidence interval (CI), 1.00 to 1.75)),
      and was unrelated to the other exposures measured. Among cases, formaldehyde and
      damp were associated with more frequent nocturnal symptoms (OR per increasing
      quartile and category, respectively, 1.45 (1.06 to 1.98) and 1.97 (1.10 to
      3.53)), significantly more so in atopic cases, but there was no effect of total
      volatile organic compounds, nitrogen dioxide, or cotinine. CONCLUSIONS: Domestic
      volatile organic compounds are not a major determinant of risk or severity of
      childhood wheezing illness, though formaldehyde may increase symptom severity.
      Indoor damp increases both the risk and severity of childhood wheezing illness.

PMID- 14586049
TI  - The role of neutrophil apoptosis in the resolution of acute lung injury in
      newborn infants.
AB  - BACKGROUND: The persistent airway neutrophilia observed in chronic lung disease
      of prematurity (CLD) may reflect inappropriate suppression of neutrophil
      apoptosis. METHODS: 134 bronchoalveolar lavage (BAL) samples were obtained from
      32 infants requiring mechanical ventilation for respiratory distress syndrome
      (RDS): 13 infants (median gestation 26 weeks, range 23 to 28) subsequently
      developed CLD (CLD group), and 19 infants (gestation 31 weeks, range 25 to 39)
      recovered fully (RDS group). A further 73 BAL samples were obtained from 20
      infants (median age 2 days, range 1 to 402) receiving extracorporeal membrane
      oxygenation (ECMO) for severe respiratory failure. RESULTS: Neutrophil apoptosis
      was increased in the RDS group (mean (SEM) neutrophil apoptosis on day 7 BAL: RDS
      17.0 (8.6)% v CLD 0.7 (0.2)% (p<0.05)). BAL fluid obtained from RDS but not CLD
      patients was proapoptotic to neutrophils (apoptosis ratio BAL fluid/saline
      control: day 1, RDS 9.8 (5.5) v CLD 1.2 (0.1) (p<0.05); day 2, RDS 4.32 (2.8) v
      CLD 0.5 (0.4) (p<0.05)). There were similar findings in the ECMO group: survivors
      had proapoptotic BAL fluid compared with non-survivors (apoptosis ratio day 1,
      survivors 7.9 (2.1) v non-survivors 2.1 (0.7) (p<0.05)). CONCLUSIONS:
      Inappropriate suppression of neutrophil apoptosis may be associated with a poor
      outcome in newborn infants with respiratory failure.

PMID- 14586050
TI  - Outpatient management of childhood asthma by paediatrician or asthma nurse:
      randomised controlled study with one year follow up.
AB  - BACKGROUND: Until now, care provided by asthma nurses has been additional to care
      provided by paediatricians. A study was undertaken to compare nurse led
      outpatient management of childhood asthma with follow up by a paediatrician.
      METHODS: Seventy four children referred because of insufficient control of
      persistent asthma were randomly allocated to 1 year follow up by a paediatrician
      or asthma nurse. The main outcome measure was the percentage of symptom-free
      days. Additional outcome measures were airway hyperresponsiveness, lung function,
      daily dose of inhaled corticosteroids (ICS), number of exacerbations, number of
      additional visits to the general practitioner, absence from school, functional
      health status, and disease specific quality of life. RESULTS: There were no
      significant differences at the end of the 1 year study period between the two
      treatment groups in percentage of symptom-free days (mean difference 2.5%; 95% CI
      -8.8 to 13.8), airway hyperresponsiveness (log10 PD20 0.06; -0.19 to 0.32),
      functional health status (10.1; -0.3 to 19.8), disease specific quality of life
      of patients (0.08; -0.9 to 0.7), and disease specific quality of life of
      caregivers (0.09; -0.2 to 0.3), nor in any other outcome parameters. Most outcome
      parameters improved considerably over the 1 year study period. These improvements
      were achieved although the daily dose of ICS was reduced by a mean of 26%
      compared with the dose received by children at referral. All parents were
      satisfied with the asthma care received. CONCLUSIONS: After initial assessment in
      a multidisciplinary clinic, childhood asthma can be successfully managed by an
      asthma nurse in close cooperation with a paediatrician. During close follow up by
      paediatrician or asthma nurse, asthma control improved despite a reduction in ICS
      dose.

PMID- 14586052
TI  - Cough frequency in children with stable asthma: correlation with lung function,
      exhaled nitric oxide, and sputum eosinophil count.
AB  - BACKGROUND: A study was undertaken to assess the correlation between cough
      frequency in asthmatic children with lung function and two non-invasive markers
      of airway inflammation. METHODS: Thirty two children of median age 12.0 years
      (interquartile range (IQR) 9.5-13.4) with stable asthma were recruited. They
      underwent spirometric testing, exhaled nitric oxide (eNO) measurement, sputum
      induction for differential cell count, and ambulatory cough monitoring over 17
      hours and 40 minutes. Coughing episodes were counted both as individual spikes
      and as clusters. RESULTS: Complete cough frequency data were available in 29
      children (90%) and their median forced expiratory volume in 1 second (FEV1) and
      eNO were 88.5% (IQR 79.5-98) and 23.9 ppb (IQR 11.4-41.5), respectively. The
      median number of cough episodes was 14 (IQR 7.0-24.0) which was significantly
      higher than that of normal children (6.7 (IQR 4.1-10.5), p<0.001). Sputum
      induction was successful in 61% of the subjects; the median induced sputum
      eosinophil count was 0.05% (IQR 0-9.0). Cough frequency was found to have a
      significant positive correlation with eNO (Spearman's r =0.781, p<0.001) but not
      with FEV1 or sputum eosinophil count (r =-0.270, p=0.157; r =0.173, p=0.508,
      respectively). CONCLUSIONS: Children with stable asthma have increased cough
      frequency compared with normal controls and cough frequency was greater during
      the day than at night. Cough may be a more sensitive marker of airway
      inflammation than simple spirometry.

PMID- 14586053
TI  - Lymphangioleiomyomatosis: a case-control study of perinatal and early life
      events.
AB  - BACKGROUND: Lymphangioleiomyomatosis (LAM), a rare disease affecting women, is
      caused by somatic mutations in the tuberous sclerosis complex genes. METHODS: A
      case-control questionnaire study was carried out examining parental and family
      history, prenatal events, and early life events to try to shed light on the
      aetiology of the condition. Forty five patients identified from a national LAM
      register completed a questionnaire and 31 were compared with 117 age and sex
      matched control subjects using conditional logistic regression. RESULTS: No
      differences were found in perinatal events, childhood infections, and parental or
      family history, except that patients were more likely to be an only child (odds
      ratio (OR) 4.3 (95% confidence interval (CI), 1.5 to 11.8)) and have a relative
      with uterine fibroids (OR 4.2 (1.4 to 13)). Patients with LAM had had fewer
      pregnancies and fewer children but no differences in miscarriage rates. A non
      matched analysis using all 45 cases and 117 controls gave similar results.
      CONCLUSIONS: No features in the family history, perinatal events, or early life
      events were detected that were associated with having LAM. Being more likely to
      be an only child and having an increased family history of uterine fibroids may,
      if confirmed, indicate some differences in reproductive function within the
      families of affected individuals.

PMID- 14586055
TI  - Plasma surfactant protein levels and clinical outcomes in patients with acute
      lung injury.
AB  - BACKGROUND: Because injury to the alveolar epithelial barrier is a characteristic
      feature of acute lung injury (ALI) and the acute respiratory distress syndrome
      (ARDS), plasma surfactant protein levels may have prognostic value. To test this
      hypothesis plasma surfactant proteins A and D (SP-A and SP-D) levels were
      measured in patients with ALI or ARDS enrolled in the NHLBI sponsored multicentre
      ARDS Network randomised controlled trial of a 6 ml/kg v 12 ml/kg tidal volume
      strategy. METHODS: Data from 565 participants in the clinical trial were used.
      Plasma levels of SP-A and SP-D were measured at baseline and on day 3 after the
      start of the mechanical ventilation protocol. The longitudinal impact of baseline
      plasma surfactant protein levels on clinical outcomes was examined by
      multivariate analysis, controlling for mechanical ventilation group, APACHE III
      score, and other clinical covariates. The effect of 6 ml/kg tidal volume
      ventilation on plasma SP-A and SP-D levels was evaluated using analysis of
      covariance. RESULTS: Baseline plasma SP-A levels were not related to any clinical
      outcome. In contrast, higher baseline plasma SP-D levels were associated with a
      greater risk of death (OR 1.21 per 100 ng/ml increment; 95% CI 1.08 to 1.35),
      fewer ventilator-free days (mean decrease -0.88 days; p=0.001), and fewer organ
      failure-free days (mean decrease -1.06 days; p<0.0001). The 6 ml/kg tidal volume
      strategy had no effect on the rise in plasma SP-A levels (p=0.91) but attenuated
      the rise in plasma SP-D levels (p=0.0006). CONCLUSIONS: Early in the course of
      ALI/ARDS an increased level of plasma SP-D is associated with a worse clinical
      outcome. The 6 ml/kg tidal volume strategy attenuated the rise of SP-D early in
      the clinical course. Taken together, these observations indicate that plasma SP
      D, a product of alveolar type II cells, is a valuable biomarker in ALI/ARDS.

PMID- 14586056
TI  - High magnification bronchovideoscopy combined with narrow band imaging could
      detect capillary loops of angiogenic squamous dysplasia in heavy smokers at high
      risk for lung cancer.
AB  - BACKGROUND: We investigated the use of high magnification bronchovideoscopy
      combined with narrow band imaging (NBI) for the detailed examination of
      angiogenic squamous dysplasia (ASD). This was carried out in relation to
      bronchial vascular patterns with abnormal mucosal fluorescence in heavy smokers
      at high risk for lung cancer. METHODS: Forty eight patients with sputum cytology
      specimens suspicious or positive for malignancy were entered into the study.
      Conventional white light and fluorescence bronchoscopic examination was first
      performed. Observations by high magnification bronchovideoscopy with conventional
      white light were made primarily at sites of abnormal fluorescence, and then
      repeated with NBI light to examine microvascular networks in the bronchial
      mucosa. Spectral features on the RGB (Red/Green/Blue) sequential videoscope
      system were changed from the conventional RGB broadband filter to the new NBI
      filter. The wavelength ranges of the new NBI filter were B1: 400-430 nm, B2: 420
      470 nm, and G: 560-590 nm. ASD tissues were also examined using a confocal laser
      scanning microscope equipped with argon-krypton (488 nm) and argon (514 nm) laser
      sources. RESULTS: The microvessels, vascular networks of various grades, and
      dotted vessels in ASD tissues were clearly observed in NBI-B1 images. Diameters
      of the dotted vessels visible on NBI-B1 images agreed with the diameters of ASD
      capillary blood vessels diagnosed by pathological examination. Capillary blood
      vessels were also clearly visualised by green fluorescence by confocal laser
      scanning microscopy. There was a significant association between the frequency of
      dotted vessels by NBI-B1 imaging and tissues confirmed as ASD pathologically
      (p=0.002). CONCLUSIONS: High magnification bronchovideoscopy combined with NBI
      was useful in the detection of capillary blood vessels in ASD lesions at sites of
      abnormal fluorescence. This may enable the discrimination between ASD and another
      pre-invasive bronchial lesion.

PMID- 14586057
TI  - Lung cancer . 10: Delivering a lung cancer service in the 21st century.
AB  - Properly organised regional centres would involve teams of interested
      cardiothoracic surgeons working with, and possibly led by, specialist pure
      thoracic surgeons to common protocols. A great deal of time would be saved by
      specialist staff reducing travelling times to outlying units. Data collection and
      administration would be greatly enhanced and the potential for collaborative work
      significantly increased. Unfortunately, there has been little if any coherent
      planning for a national strategy for the delivery of such care in the United
      Kingdom.

PMID- 14586058
TI  - Cough . 2: Chronic cough in children.
AB  - Chronic cough is a common problem in childhood. Viral infections are the most
      prevalent cause, but other rarer disorders should be excluded whenever cough
      appears unusually severe and/or frequent, and when there is evidence of failure
      to thrive and growth retardation. The younger the child, the more the need to
      exclude underlying disease at an early stage. Passive smoking is an important
      contributor to chronic cough in children. Chronic productive cough with purulent
      sputum is always reason for concern in children and is not common as a symptom of
      asthma. More or less specific diagnoses in children include cystic fibrosis,
      aspirated foreign body, congenital anatomic abnormalities and primary ciliary
      dyskinesia.

PMID- 14586060
TI  - Erdheim-Chester disease: pulmonary infiltration responding to cyclophosphamide
      and prednisolone.
AB  - Erdheim-Chester disease is a rare multisystem histiocytic disorder in which death
      most commonly results from pulmonary or cardiac involvement. We report the case
      history of a 55 year old man with this condition with extensive and progressive
      pulmonary disease. He had no response to prednisolone alone, but treatment with
      prednisolone plus cyclophosphamide was associated with a rapid improvement in
      symptoms, lung function, and the chest radiographic appearance. He subsequently
      showed a symptomatic, functional, and radiological deterioration, followed by a
      marked slowing in the rate of decline. He currently remains stable 41 months
      after treatment was initiated. This is the first report of pulmonary Erdheim
      Chester disease showing improvement in both lung function and symptoms with any
      form of treatment.

PMID- 14586061
TI  - Management of COPD.

PMID- 14586062
TI  - Huntington's disease.
AB  - In this case study, we describe the symptoms, neurological exam,
      neuropsychological test results, and brain pathology of a man who died with
      Huntington's disease (HD). HD is a rare neurodegenerative disease. Like other
      movement disorders involving the basal ganglia, HD affects motor, cognitive, and
      psychiatric functioning. The disease follows an autosomal dominant pattern of
      inheritance, with onset of symptoms most commonly occurring in the late 30s or
      early 40s, as in this patient. HD is caused by an unstable expansion of the
      trinucleotide CAG, coding for glutamine, on chromosome 4. Despite knowledge of
      the gene mutation responsible for HD, no definitive treatment is currently
      available to slow or halt progression of the disease. However, symptomatic
      treatment can significantly improve the quality of life for patients with HD.

PMID- 14586063
TI  - Detangling Alzheimer's disease. New insights into the biological bases of the
      most common cause of dementia are pointing to better diagnostics and possible
      therapeutics.
AB  - Alzheimer's disease afflicts 4.5 million people in the United States, and the
      number is expected to rise to 16 million by the year 2050, as the population
      ages. Researchers are scrambling to find genetic risk factors, decipher disease
      mechanisms, and develop reliable diagnostic tests that detect the illness at its
      earliest, potentially most treatable stage. Using these findings, they hope to
      devise new therapeutic approaches. Current clinical trials are assessing novel
      techniques that stall or reverse Alzheimer-like neuropathology in mice.

PMID- 14586064
TI  - Controversies in papillary microcarcinoma of the thyroid.
AB  - Papillary thyroid carcinomas that are smaller than 1 cm are classified as
      papillary microcarcinomas (PMC). These lesions are frequently detected as
      incidental findings on autopsy or in surgical specimens. They are often
      multifocal. The relationship between PMC and clinical papillary thyroid carcinoma
      (PTC) is not clear. In patients with clinical thyroid cancer, PMC may represent
      intrathyroidal metastases; they may be the earliest form of future large lesions.
      These uncertainties raise questions about appropriate clinical management of
      patients with these lesions. Review of the literature substantiates the argument
      that clinically evident PTC may be distinctly different from solitary or
      multifocal PMC in terms of etiology and biologic behavior, supporting a
      conservative approach to management.

PMID- 14586065
TI  - Pheochromocytoma: rediscovery as a catecholamine-metabolizing tumor.
AB  - Catecholamine-producing tumors are rare neoplasms derived mainly from chromaffin
      cells of the adrenal medulla (pheochromocytomas) or, in about 10% of cases, from
      paraganglia (paragangliomas). Diagnosis of these tumors relies heavily on
      measurements of urinary or plasma catecholamines or catecholamine metabolites.
      The metabolites are usually thought to be produced after release of
      catecholamines into the bloodstream. This, however, ignores observations of over
      40 yr ago that catecholamines are metabolized within pheochromocytoma tumor
      cells. Development of improved methods for measurement of catecholamine
      metabolites, in particular, plasma concentrations of free normetanephrine and
      metanephrine, has reestablished the importance of intratumoral catecholamine
      metabolism. In patients with pheochromocytoma, over 90% of the elevations in
      plasma free normetanephrine and metanephrine result from metabolism of
      catecholamines within pheochromocytoma tumor cells. This process occurs
      continuously and independently of variations in catecholamine release. As a
      consequence, measurements of plasma concentrations and urinary outputs of
      normetanephrine and metanephrine provide more reliable methods for diagnosis of
      pheochromocytoma than measurements of the parent amines. Rediscovery of the
      importance of intratumoral catecholamine metabolism is leading to a reevaluation
      of the procedures used to diagnose pheochromocytoma. This review provides an
      update on the diagnosis of pheochromocytoma, with emphasis on identifying and
      correcting relevant misconceptions about catecholamine metabolism.

PMID- 14586066
TI  - Telomerase activity in well-differentiated papillary thyroid carcinoma correlates
      with advanced clinical stage of the disease.
AB  - Clinical relevance and stage correlation of telomerase activity in well
      differentiated papillary thyroid carcinoma (WD PTC) has not been well determined,
      as its reported activity could be due to the analysis of tumors with lymphocytic
      infiltrates or aggressive variants of papillary carcinomas. We conducted a
      prospective study of telomerase activity in WD PTC without inflammatory
      infiltrates and correlated it with clinical stage. Fifty WD PTCs were analyzed
      for telomerase activity by PCR-based TRAP (telomeric repeat amplification
      protocol) assay. Results were correlated with stage and other clinicopathologic
      variables. Twenty-one (42%) WD PTCs demonstrated telomerase activity. The enzyme
      was detected more frequently in stage III/IVa WD PTCs (p = 0.02) and in tumors
      with extra thyroidal extension (p = 0.04). The risk of presenting advanced
      disease (stage III/IVa) and extrathyroidal growth was significantly increased in
      telomerase-positive tumors (p = 0.01; odds ratio [OR] 4.4 [95%CI 1.3-14.7]) and
      (p = 0.04; OR 3.6 [95%CI 1.1-11.7]), respectively. Also, a correlation was found
      between telomerase activity and age. There was no correlation of telomerase
      activity with gender, histologic variant, tumor size, or cervical lymph node
      metastasis. Telomerase activity was observed in 42% of WD PTC and was detected
      more frequently in AJCC TNM stage III/IVa cases. This finding suggests that
      telomerase deregulation could be involved in tumor progression.

PMID- 14586068
TI  - Immunohistochemical detection of somatostatin receptor subtypes in "clinically
      nonfunctioning" pituitary adenomas.
AB  - Pituitary tumors diagnosed before surgery as "non-functioning" in fact represent
      a heterogenous group, the majority of which express glycoprotein hormones or
      their free subunits. It is known that some of them expresses somatostatin
      receptors, but the data available until now rarely refer to the receptor subtype.
      Five different subtypes of somatostatin receptors (sst1-5) have been cloned. We
      studied 18 pituitary tumors diagnosed before surgery as "non-functioning." After
      the surgery the tumors were immunostained with antibodies against pituitary
      hormones and alpha subunit as well as with antibodies against the somatostatin
      receptor proteins 1-5. Thirteen adenomas expressed immunoreactivity for FSH, LH,
      and/or alpha subunit and were classified as gonadotroph adenomas. The remaining
      five adenomas were immunonegative for all the examined pituitary hormones and
      were diagnosed as null cell adenomas. All the adenomas of both the groups showed
      immunopositivity for at least three receptor subtypes. The strongest
      immunopositivity was found in both groups with anti-sst1 and anti-sst5
      antibodies. The marked immunopositivity was also revealed in both groups with
      anti-sst2B antibody. On the other hand, the sst2A immunopositivity was weak or
      absent in a majority of tumors. The main difference between two groups was in the
      sst4 receptor subtype which was absent in all but two gonadotroph adenomas but
      present in all but one null cell adenoma. These findings suggest that "non
      functioning" pituitary adenomas are potential candidates for therapy with
      somatostatin analogs targeted mainly to the receptor subtypes 1 and 5.

PMID- 14586067
TI  - Merkel cell carcinomas: expression of S-phase kinase-associated protein 2 (Skp2),
      p27, and proliferation markers.
AB  - Merkel cell carcinomas are rare and aggressive tumors about which the expression
      of cell cycle regulatory proteins are not well known. We evaluated the
      clinicopathologic features of Merkel cell carcinomas and examined the expression
      of the cell cycle regulatory markers p27 and S-phase kinase-associated protein 2
      (Skp2) and the proliferation markers Ki-67 and DNA topoisomerase II alpha (topo
      II alpha) in a group of these tumors. Thirty-nine cases of Merkel cell carcinoma
      were studied, 19 from the Mayo Clinic, Rochester, MN, and 20 from the University
      of Torino, Torino, Italy. Although the University of Torino patients tended to be
      slightly older at time of surgery compared to the Mayo Clinic patients, no
      clinical, pathologic, or immunohistochemical feature was statistically
      significantly different between the two groups. Of the 39 patients, 20 were male
      and 19 were female. The age at surgery averaged 72 yr. Formalin-fixed paraffin
      embedded archival tissues from the 39 Merkel cell carcinomas were analyzed by
      immunohistochemistry for p27, Skp2, Ki-67, and topo II alpha with the avidin
      biotin peroxidase system. The distribution of immunoreactivity was analyzed by
      quantifying the percentage of positive nuclei, which was expressed as the
      labeling index. There was a statistically significant inverse relationship
      between p27 and Skp2 (p = 0.005). Most tumors with increased levels of Skp2 were
      associated with reduced p27, and tumors with high levels of p27 expression were
      associated with reduced levels of Skp2. These results suggest that Skp2 regulates
      p27 expression in Merkel cell carcinomas. Tumors showing increased Skp2
      expression were not always correlated with increased proliferation as evaluated
      by Ki-67 and topo II alpha, suggesting that Skp2 may be involved in Merkel cell
      tumorigenesis, but that other factors may also influence cell proliferation in
      these tumors.

PMID- 14586069
TI  - Microvascular structural entropy: a novel approach to assess angiogenesis in
      pituitary tumors.
AB  - Entropy, a measure of the degree of disorder in a system, has recently been used
      in different morphologic studies to quantify regularity. Our aims were (a) to
      study the structural organization of the microvascular bed in prolactin (PRL)
      producing adenomas and carcinomas, the most vascularized of pituitary tumors, by
      assessing microvascular structural entropy (MSE), and (b) to determine whether
      the degree of disorder of the capillary bed correlates with tumor cell
      proliferation as estimated by MIB-1 labeling, microvessel density (MVD), the most
      widely used method of quantifying blood vessel formation, and various
      clinicopathologic parameters (gender, age, tumor size and invasiveness). The
      morphometric study demonstrated statistically significant differences in MIB-1
      labeling, MVD, and MSE between PRL-producing adenomas and carcinomas. Unlike MIB
      1 labeling index (PRL-producing adenomas 1.5 +/- 0.27; carcinomas 15.0 +/- 4.04)
      and MVD (PRL-producing adenomas 2.7 +/- 0.34; carcinomas 4.2 +/- 0.72), the MSE
      values were significantly higher in adenomas (171.5 +/- 25.37) than in carcinomas
      (67.9 +/- 17.45). These results indicate that PRL-producing carcinomas have a
      less chaotic distribution of vessels than benign adenomas. In contrast to a lack
      of correlation between microvessel density and other morphometric parameters, a
      strong negative correlation was found between MSE and MIB-1 labeling index (r =
      0.511, p = 0.003). It thus appears that regular, less chaotic microvascular
      geometry contributes to increased proliferative activity in PRL cell tumors.
      Analysis of MSE may provide an independent parameter of tumor behavior, and
      contributes to a better understanding of the role of microvasculature in
      pituitary tumor progression.

PMID- 14586070
TI  - Calcitonin immunoreactivity in neoplastic and hyperplastic parathyroid glands: an
      immunohistochemical study.
AB  - BACKGROUND: Previous studies have established that calcitonin (CT) and the
      calcitonin generelated peptide (CGRP) are synthesized and stored in subsets of
      hyperplastic parathyroid cells that also contain chromogranin B (Schmid, KW, et
      al. Lab Invest 73:90, 1995). The purpose of the current study was to determine
      whether other generic but variably expressed neuroendocrine markers, i.e.,
      synaptophysin (SYN) and CD57 (Leu7), are also present in normal, hyperplastic,
      and neoplastic parathyroid tissue and to assess their relationships to the
      presence of CT. DESIGN: Immunoperoxidase stains for chromogranin A (CgA),
      chromogranin B (CgB), SYN, CD57, and CT were performed on 54 hyperplastic, 17
      neoplastic (adenoma), and 16 normal parathyroid glands. Sequential sections were
      stained with antibodies to CgA, CgB, SYN, CD57, and CT using standard avidin
      biotin-peroxidase techniques. RESULTS: CgA was diffusely expressed in all normal,
      hyperplastic, and neoplastic glands. In hyperplasia, CgB was variably expressed
      in 6 cases (11%), SYN in 6 (11%), CD57 in 15 (28%), and CT in 8 (15%). In
      adenomas, CgB was variably expressed in 3 (17%), SYN in 3 (17%), CD57 in 4 (23%),
      and CT in 4 (23%). All normal glands were negative for CgB, SYN, and CT, while
      CD57 was variably expressed in 17%. Of the 12 glands that were CT positive, 8
      were also positive for CgB, 2 for SYN, and 9 for CD57. Four glands that were
      strongly and diffusely positive for CT were CgB and SYN negative. CONCLUSIONS:
      CgB, SYN, and CD57 are markers for subsets of hyperplastic and neoplastic
      parathyroid glands. CT is also expressed in a significant proportion of
      hyperplastic and neoplastic parathyroid glands, and may be independent of the
      presence of CgB, SYN, or DD57. The significance of these findings in relationship
      to the abnormal calcium metabolism in patients with parathyroid hyperplasia
      remains to be determined.

PMID- 14586071
TI  - Immunohistochemical evaluation of vasopressin expression in breast fibrocystic
      disease and ductal carcinoma in situ (DCIS).
AB  - We previously found that expression of the vasopressin gene is a common feature
      of human breast cancer. In the present study we first examined 21 different cases
      of benign fibrocystic breast disease for vasopressin expression using
      immunohistochemistry and antibodies directed against vasopressin (anti-VP) and
      against vasopressin-associated glycopeptide (anti-VAG). All cases examined were
      negative for vasopressin gene expression using these antibodies. Alternatively,
      we examined 16 cases of breast ductal carcinoma in situ (DCIS) using the second
      of these antibodies (anti-VAG), and all of these cases were positive for
      vasopressin gene expression. Our results suggest that products of vasopressin
      gene expression are not markers of cellular proliferation in the breast, and
      might rather represent an early part of the carcinogenic process in this tissue.

PMID- 14586072
TI  - Diagnostic value of frozen section examination in thyroid nodule--surgery at the
      Shariati Hospital (1997-2000).
AB  - INTRODUCTION: There is controversy regarding the use and accuracy of frozen
      section (FS) in managing thyroid nodules. We compared the diagnostic value of FS
      with that of permanent histopathology examination and fine needle aspiration
      (FNA). MATERIALS AND METHODS: Permanent, FS, and FNA sample reports were compared
      in 214 patients between 1997 and 2000. FS, FNA, and permanent pathology (gold
      standard) results were compared using McNemar's test. RESULTS: 160 women and 54
      men (mean age: 42.3 +/- 5.4 yr) took part in the study; 163 patients (76%) had
      benign and 51 (24%) malignant lesions; 76% of our thyroid cancer cases were
      papillary, 13.5% follicular, 6% medullary carcinoma, 4% Hurthle cell carcinoma,
      and 0.5% anaplastic carcinoma. FNA yielded definite results in 150 patients
      (sensitivity 72%, specificity 96%, and precision 90%). In 64 patients with
      equivocal FNA, FS was performed (sensitivity 36%, specificity 73%, and precision
      85%). The observed difference between FNA and FS was not statistically
      significant. DISCUSSION: When FNA results are inconclusive, FS does not provide
      any further information. In suspected cases of papillary, undifferentiated, or
      medullary carcinomas, FS can confirm FNA findings and guide surgical therapy.

PMID- 14586073
TI  - Concurrent lymph node metastases of medullary and papillary thyroid carcinoma in
      a case with RET oncogene germline mutation.
AB  - We report the case of a 72 yr-old woman who underwent total thyroidectomy and
      resection of neck lymph nodes because of a firm nodule in the right lobe, which
      was consistent with medullary thyroid carcinoma (MTC) on cytological examination.
      Histology showed multifocal bilateral MTC; a 2 mm papillary thyroid carcinoma
      (PTC) was also detected in the right lobe, next to a focus of MTC; five cervical
      lymph nodes contained MTC. In one right perithyroidal lymph node, concurrent
      metastases of MTC and PTC were demonstrated. DNA analysis showed a point mutation
      in exon 14 at codon 804 of the RET proto-oncogene locus, as frequently found in
      cases of familial MTC (FMTC). To our knowledge, this case represents the first
      documented case of concurrent lymph node metastases of MTC and PTC in a patient
      with RET proto-oncogene germline mutation. We report this unique case, discuss
      related thyroid malignancies, and suggest possible underlying pathogenetic
      mechanisms.

PMID- 14586074
TI  - Systematic prediction of new ferroelectrics in space groups P3(1) and P3(2).
AB  - Release 2002/2 of the Inorganic Crystal Structure Database (FIZ Karlsruhe,
      Germany, and Institute Laue-Langevin, Grenoble, France) contains 62 entries in
      space group P3(1) and ten entries in space group P3(2) for 49 different materials
      including eight families with two or more isostructural members. The structural
      criteria for ferroelectricity are satisfied for 16 new structure types at a
      confidence level that depends on the reliability of each determination.
      LaBGeO(5), a mineral with stillwellite structure, was previously reported as
      ferroelectric and forms an additional family with seven other members or related
      structures that satisfy the criteria. Ten structures reported in space group
      P3(1) or P3(2) are dubious or incorrect, with atomic coordinates that satisfy
      supergroup symmetry. One material is probably pyroelectric but is unlikely to
      become ferroelectric, and three others are either incompletely solved or
      incompletely refined. Among the predicted new ferroelectrics are Cu(2)BaGeS(4,)
      Fe(3)(Fe,Si)O(4)(OH)(5), Se(4)S(5), K(2)HCr(2)AsO(10), IV-RbNO(3),
      Rb(2)Sc(NO(3))(5), Na(3)ReO(5), Nd(14)(GeO(4))(2)(BO(3))(6)O(8), CsHgCl(3,)
      Ba(2)Cu(2)AlF(11), KYF(4), SrS(2)O(6).4H(2)O, Cu(3)PbTeO(6)(OH)(2), ReH(CO)(4),
      Ni(2)(NH(3))(9)Mo(CN)(8).2H(2)O and the 6T polytype of
      Ca(1.89)Ta(1.80)Sm(0.16)Ti(0.10)O(7), in addition to beta-LaBSiO(5), PbBAsO(5)
      and BaBAsO(5) in the stillwellite family.

PMID- 14586075
TI  - Structure-property correlation over five phases and four transitions in
      Pb5Al3F19.
AB  - The calorimetric and dielectric properties of Pb(5)Al(3)F(19) in the five phases
      stable under ambient pressure are correlated with structure for fuller
      characterization of each phase. The first-order transition between ferroelectric
      phase V and antiferroelectric phase IV at T(V,IV) = 260 (5) K exhibits a thermal
      hysteresis of 135 (5) K on heating, with a maximum atomic displacement
      Delta(xyz)(max) = 1.21 (6) A; the transition from phase IV to ferroelastic phase
      III at 315 (5) K is also first order but with a thermal hysteresis of 10 (5) K
      and Delta(xyz)(max) = 0.92 (7) A; that from phase III to paraelastic phase II at
      360 (5) K is second order without hysteresis and has Delta(xyz)(max) = 0.69 (4)
      A; and the transition from phase II to paraelectric phase I at 670 (5) K is
      second or higher order, with Delta(xyz)(max) = 0.7 (4) A. The measured entropy
      change DeltaS at T(V,IV) agrees well with DeltaS as derived from the increased
      configurational energy by Stirling's approximation. For all other phase
      transitions, 0.5 > or = DeltaS > 0 J mol(-1) K(-1) is consistent with an entropy
      change caused primarily by the changes in the vibrational energy. The structure
      of phase III is determined both by group theoretical/normal mode analysis and by
      consideration of the structures of phases II, IV and V reported previously;
      refinement is by simultaneous Rietveld analysis of the X-ray and neutron
      diffraction powder profiles. The structure of prototypic phase I is predicted on
      the basis of the atomic arrangement in phases II, III, IV and V. The introduction
      of 3d electrons into the Pb(5)Al(3)F(19) lattice disturbs the structural
      equilibrium, the addition of 0.04% Cr(3+) causing significant changes in atomic
      positions and increasing T(IV,III) by approximately 15 K. Substitution of Al(3+)
      by 20% or more Cr(3+) eliminates the potential minima that otherwise stabilize
      phases IV, III and II.

PMID- 14586076
TI  - Features of the electron density in magnesium diboride: reconstruction from X-ray
      diffraction data and comparison with TB-LMTO and FPLO calculations.
AB  - Features of the electron density in MgB(2) reconstructed from room-temperature
      single-crystal X-ray diffraction intensities using a multipole model are
      considered. Topological analysis of the total electron density has been applied
      to characterize the atomic interactions in magnesium diboride. The shared-type B
      B interaction in the B-atom layer reveals that both sigma and pi components of
      the bonding are strong. A closed-shell-type weak B-B pi interaction along the c
      axis of the unit cell has also been found. The Mg-B closed-shell interaction
      exhibits a bond path that is significantly curved towards the vertical Mg-atom
      chain ([110] direction). The latter two facts reflect two sorts of bonding
      interactions along the [001] direction. Integration of the electron density over
      the zero-flux atomic basins reveals a charge transfer of approximately 1.4 (1)
      electrons from the Mg atoms to the B-atom network. The calculated electric-field
      gradients at nuclear positions are in good agreement with experimental NMR
      values. The anharmonic displacement of the B atoms is also discussed.
      Calculations of the electron density by tight-binding linear muffin-tin orbital
      (TB-LMTO) and full-potential non-orthogonal local orbital (FPLO) methods confirm
      the results of the reconstruction from X-ray diffraction; for example, a charge
      transfer of 1.5 and 1.6 electrons, respectively, was found.

PMID- 14586077
TI  - Structures of Na0.74WO3.
AB  - The structures of the four phases exhibited by Na(0.74)WO(3), sodium tungstate,
      with a change in temperature have been refined from powder diffraction patterns
      obtained on the high-resolution powder diffractometer (HRPD), ISIS, Rutherford
      Appleton Laboratory, England. At temperatures above 430 K, the stable phase has
      the ideal perovskite structure, with space group Pm3;m (No. 221). Below that
      temperature, the octahedra are tilted about pseudocubic <100> directions; the
      tilts are produced by the condensation of the normal modes of vibration of the
      octahedra in the high-temperature cubic phase. Using Glazer's notation, the tilt
      system undergoes the following sequence: a+a+a+ (293K)-->a+a+a0(343K)-
      >a0a0a+(430K)-->a0a0a0. The structural refinements presented here confirm the
      sequence of the transitions first proposed by Clarke [(1977). Phys. Rev. Lett.
      39, 1550-1553]. This is the first time that a structure determination of a
      perovskite with the tilt system a+a+a0 has been reported in the literature. In
      addition, we evaluate the weights, or importance, of the condensed modes in each
      low-temperature phase.

PMID- 14586078
TI  - Phase transitions in KTP isostructures: correlation between structure and Tc in
      germanium-doped RbTiOPO4.
AB  - Crystals of germanium-doped rubidium titanyl phosphate,
      Rb(2)(Ti)(Ge(0.121)Ti(0.879))O(2)(PO(4))(2) (GeRTP#1) and
      Rb(2)(Ge(0.125)Ti(0.875))(Ge(0.225)Ti(0.775))O(2)(PO(4))(2) (GeRTP#2), have been
      structurally characterized from X-ray diffraction data at room temperature. In
      addition, a third structure, Rb(2)(TiO)(2)(PO(4))(2) (RTP), has been
      reinvestigated. The exchange of titanium for germanium results in a less
      distorted octahedral coordination around the two crystallographically independent
      titanium sites. Additionally, rubidium split-cation positions have been found in
      these doped RTP crystals. Dielectric measurements show that the phase-transition
      temperature, T(c), decreases with increasing germanium concentration, and a
      direct correlation between the room-temperature split of the rubidium cations and
      T(c) has been discovered. General trends regarding the relationship between the
      room-temperature structures of KTP-like compounds and their T(c) values are
      discussed.

PMID- 14586079
TI  - Sodium percarbonate between 293 and 100 K.
AB  - Sodium carbonate perhydrate, Na(2)CO(3).1.5H(2)O(2), commonly known as sodium
      percarbonate, has been structurally characterized at temperatures ranging from
      293 down to 100 K. As the temperature drops, there is a reversible phase change
      between 250 and 240 K, in which the crystallographic mirror plane of the room
      temperature space group, Cmca, is lost, transforming it to Pbca. This
      transformation is accompanied by a reversal in the expansion coefficient of cell
      side b, which, like the other two sides, initially contracts on cooling. The two
      crystallographically independent hydrogen peroxide sites undergo the largest
      change, where the disorder seen at room temperature gradually diminishes and is
      almost completely absent at 100 K, thus indicating dynamic rather than static
      disorder. It is noteworthy that, despite Cmca being the preferred room
      temperature space group in the current work, two previous single-crystal studies
      rejected this space group in favour of non-centrosymmetric Aba2 [Carrondo et al.
      (1977). J. Chem. Soc. Dalton Trans. pp. 2323-2331; Adams & Pritchard (1977). Acta
      Cryst. B33, 3650-3653]. A re-evaluation of these determinations indicates that
      they are identical to the current structure and should be re-assigned to Cmca.

PMID- 14586080
TI  - Synthesis and structure of M0.5Bi3P2O10 (M = Ca, Sr, Ba, Pb) series.
AB  - A series of M(0.5)Bi(3)P(2)O(10) compounds with M = Ca, Sr, Ba and Pb have been
      synthesized in MO-Bi(2)O(3)-P(2)O(5) ternary systems by the ceramic method and
      the crystal structures were then solved using single-crystal X-ray diffraction
      data. These compounds are isostructural with Bi(6.67)P(4)O(20) (triclinic, space
      group P1;, Z = 2). The structures consist of infinite chains of Bi(2)O(2) units
      along the c axis formed by linking BiO(8) and BiO(6) polyhedra. These chains are
      interconnected by MO(8) polyhedra forming two-dimensional layers in the ac plane.
      The phosphate tetrahedra are sandwiched between these layers.

PMID- 14586081
TI  - Structural investigation of the Na-Fe-Mo-O system.
AB  - Four new crystalline structures within the Na-Fe-Mo-O system are reported: sodium
      tetrairon pentamolydate (1), NaFe(4)(MoO(4))(5), alpha-sodium diiron trimolybdate
      (2), alpha-NaFe(2)(MoO(4))(3), beta-sodium diiron trimolybdate (3), beta
      NaFe(2)(MoO(4))(3), trisodium diiron trimolybdate (4), Na(3)Fe(2)(MoO(4))(3). All
      these structures belong to orthomolybdate class of compound and are described as
      networks of [FeO(6)] octahedra and [MoO(4)] tetrahedra. They are compared with
      each other and with other related structures.

PMID- 14586082
TI  - Temperature-resolved study of the structural behaviour of nickel octahexyl
      phthalocyanine up to the liquid crystal transition.
AB  - This paper describes a temperature-resolved crystallographic investigation into
      the behaviour of the title compound as the temperature is increased stepwise from
      room temperature up to 418 K, which is the temperature at which a transition to a
      discotic columnar mesophase takes place. The experiments were conducted using
      synchrotron radiation on Station 9.8 at the SRS at the Daresbury Laboratory. An
      intermediate transition to a less well ordered crystal form was seen at 326 K and
      differential scanning calorimetry (DSC) measurements confirmed the transition
      temperature of this change. Also, a new improved room-temperature crystal
      structure was obtained, as well as further structure determinations at 323, 328
      and 353 K. These showed that as the mobility, particularly of the hexyl groups,
      increases with temperature, the packing of the molecules adjusts from
      pseudohexagonal layers to a rectangular arrangement.

PMID- 14586083
TI  - The phases of [(CH3)4N](ClO4) at low temperature.
AB  - The low-temperature crystal structures of tetramethylammonium perchlorate,
      [(CH(3))(4)N](ClO(4)), are analysed. At 210 K, a collection of 376 unique
      reflections on a single crystal gave R = 0.0567 for space group P4/nmm, with a(1)
      = 8.2376 (14), c(1) = 5.8256 (12) A and Z = 2, where the ClO(4) groups are
      disordered over four orientations. Below T(c) = 170 K, these groups order in four
      sublattices, each ion gradually choosing one unique orientation. At 150 K, the
      crystal is microtwinned. 1389 unique reflections were refined in the orthorhombic
      space group P2(1)2(1)2, with a(3) = 11.714 (3), b(3) = 11.784 (3), c(3) = 5.8265
      (9) A, Z = 4 and R = 0.087. At 30 K, Rietveld refinement gave the same structure
      as is found at 150 K, with a clear difference between a(3) and b(3) [a(3) =
      11.566 (2), b(3) = 11.806 (2) and c(3) = 5.729 (1) A]. The structural models and
      the phase transition are explained on the basis of electrostatic octopole
      octopole interactions among the ClO(4) groups within layers perpendicular to the
      c axis. The order parameters of the low-temperature phase are discussed in
      relation to the structural results.

PMID- 14586084
TI  - A database survey of molecular and crystallographic symmetry.
AB  - The point of contact between molecular and crystallographic symmetries is that of
      the Wyckoff position, the position at which a molecule resides in a crystal
      structure. These Wyckoff positions may have the same symmetry as the molecules,
      some symmetry in common with the molecules or no symmetry at all. Using
      CSDSymmetry [Yao et al. (2002). Acta Cryst. B58, 640-646], a relational database
      containing information pertaining to the symmetry of molecules and the crystal
      structures that play host to them, the distribution of molecules over Wyckoff
      positions and the occupancy of Wyckoff positions in crystal structures is
      presented. Analysis of these data has led to the characterization of some
      relationships between molecular and crystallographic symmetry.

PMID- 14586085
TI  - X-ray studies on crystalline complexes involving amino acids and peptides. XLI.
      Commonalities in aggregation and conformation revealed by the crystal structures
      of the pimelic acid complexes of L-arginine and DL-lysine.
AB  - The complexes of L-arginine and DL-lysine with pimelic acid are made up of singly
      positively charged zwitterionic amino acid cations and doubly negatively charged
      pimelate ions in a 2:1 ratio. In both structures, the amino acid molecules form
      twofold symmetric or centrosymmetric pairs that are stabilized by hydrogen bonds
      involving alpha-amino and alpha-carboxylate groups. In the L-arginine complex,
      these pairs form columns along the shortest cell dimension, stabilized by
      intermolecular hydrogen bonds involving alpha-amino and alpha-carboxylate groups.
      The columns are connected by hydrogen bonds and water bridges to give rise to an
      amino acid layer. Adjacent layers are then connected by pimelate ions. Unlike
      molecular ions aggregate into alternating distinct layers in the DL-lysine
      complex. In the amino acid layer, hydrogen-bonded lysinium dimers related by a
      glide plane are connected by hydrogen bonds involving alpha-amino and alpha
      carboxylate groups into head-to-tail sequences. Interestingly, the aggregation
      pattern observed in L-arginine hemipimelate monohydrate is very similar to those
      in DL-arginine formate dihydrate, DL-arginine acetate monohydrate and L-arginine
      hemiglutarate monohydrate. Similarly, the aggregation of amino acid molecules is
      very similar in DL-lysine hemipimelate 0.53-hydrate, DL-lysine formate and DL
      lysine hydrochloride. The complexes thus demonstrate how, in related structures,
      the effects of a change in composition, and sometimes even those of reversal in
      chirality, can be accommodated by minor adjustments in essentially the same
      aggregation pattern. It also transpires that the conformation of the argininium
      ion is the same in the four argininium complexes; the same is true about the
      conformation of the lysinium ion in the three lysinium complexes. This result
      indicates a relation between, and mutual dependence of, conformation and
      aggregation.

PMID- 14586086
TI  - Investigation of diffraction line broadening due to compositional fluctuations in
      L-alanine-doped triglycine sulfate.
AB  - Broadening of X-ray powder diffraction peaks as a result of compositional
      disorder in L-alanine-doped triglycine sulfate crystals is investigated using the
      Williamson-Hall method. The analysis indicates that L-alanine substitution in
      triglycine sulfate crystals leads to anisotropic strain in the crystal.

PMID- 14586087
TI  - A neutron diffraction study of xylitol: derivation of mean square internal
      vibrations for H atoms from a rigid-body description.
AB  - A neutron diffraction study of xylitol (C(5)O(5)H(12)) is presented. The nuclear
      anisotropic displacement parameters have been analysed showing that the carbon
      oxygen skeleton conforms to a rigid-body (TLS) description. Applying this TLS
      model to the xylitol H atoms allows characterization of the internal molecular
      displacements of the H nuclei, assuming that the observed H nuclear mean-square
      displacements are a sum of the internal displacements and rigid-body
      displacements. These internal molecular displacements are very similar for
      chemically equivalent H atoms and in good agreement with the values obtained by
      other methods. In all cases the smallest eigenvector of the residual mean-square
      displacement tensor is almost parallel to the X-H bond. The use of ab initio
      calculations to obtain the internal vibrations in xylitol is discouraging.
      Another 12 structures extracted from the literature which have been investigated
      by neutron diffraction were subjected to a similar analysis. The results for the
      nine compounds investigated at low temperature conform to the results from
      xylitol and provide estimates of the internal vibrations of H atoms in a range of
      chemical environments.

PMID- 14586088
TI  - Supramolecular aggregation in 4,4'-bipyridin-1,1'-ium dichloride, 4,4'-bipyridin
      1,1'-ium dinitrate and 4,4'-bipyridin-1-ium bromide.
AB  - 4,4'-Bipyridin-1,1'-ium dichloride [C(10)H(10)Cl(2)N(2) (I)] and 4,4'-bipyridin
      1,1'-ium dinitrate [C(10)H(10)N(4)O(6) (II)] have been prepared and the crystal
      structures determined at 90.0 (2) K. Molecules of (I) are linked by two chlorine
      bridged, three-centered N-H...Cl hydrogen bonds into chains along the b axis. The
      chains are coupled by weak C-H...Cl interactions into a molecular ladder along
      the c direction. In (II) each nitrate is coordinated to four bipyridinium ions
      through the interplay of the N-H...O and C-H...O contacts, resulting in a three
      dimensional zigzag sheet on the ab plane. The sheets stack along the c axis. In
      4,4'-bipyridin-1-ium bromide monohydrate [C(10)H(9)N(2)(+).Br(-).H(2)O (III)] the
      bipyridinium ions are linked by three-center N-H.N' hydrogen bonds in a head-to
      tail fashion to form chains along the b axis. The chains are linked by C-H...Br
      and C-H...OH2 into a three-dimensional framework.

PMID- 14586089
TI  - Monitoring structural transformations in crystals. 5. A topotactic [2 + 2]
      photodimerization reaction.
AB  - The structural changes in a crystal of 5-benzylidene-2-(4
      chlorobenzyl)cyclopentanone during [2 + 2]-photodimerization were monitored by
      means of X-ray diffraction. It was observed that the monomers moved gradually
      from the position occupied in the crystal at the initial stage of the
      photoreaction and the dimers moved towards the position assumed at the final
      step. The movements of the molecules possess a rotational component. Moreover,
      with the progress of the phototransformation the monomers in the reacting pair
      gradually move closer and change their relative orientation to resemble more the
      product molecule. The behaviour of the molecules and also the variation of the
      cell constants for the studied compound were compared with data for 5-benzylidene
      2-benzylcyclopentanone.

PMID- 14586090
TI  - Can we predict lattice energy from molecular structure?
AB  - By using simply the numbers of occurrences of different atom types as
      descriptors, a conceptually transparent and remarkably accurate model for the
      prediction of the enthalpies of sublimation of organic compounds has been
      generated. The atom types are defined on the basis of atomic number,
      hybridization state and bonded environment. Models of this kind were applied
      firstly to aliphatic hydrocarbons, secondly to both aliphatic and aromatic
      hydrocarbons, thirdly to a wide range of non-hydrogen-bonding molecules, and
      finally to a set of 226 organic compounds including 70 containing hydrogen-bond
      donors and acceptors. The final model gives squared correlation coefficients of
      0.925 for the 226 compounds in the training set and 0.937 for an independent test
      set of 35 compounds. The success of such a simple model implies that the enthalpy
      of sublimation can be predicted accurately without knowledge of the crystal
      packing. This hypothesis is in turn consistent with the idea that, rather than
      being determined by the particular features of the lowest-energy packing, the
      lattice energy is similar for a number of hypothetical alternative crystal
      structures of a molecule.

PMID- 14586091
TI  - Characteristics of an anaerobic, syntrophic, butyrate-degrading bacterium in
      paddy field soil.
AB  - The number of syntrophic butyrate-degrading bacteria in a flooded paddy field
      soil was 1.7 x 10(3) MPN/g dry soil. Butyrate was degraded to acetate and methane
      when paddy soils were incubated anaerobically with the addition of butyrate.
      However, butyrate degradation was completely suppressed by the addition of the
      specific inhibitor of methanogenesis, 2-bromoethanesulfonate (BES) to the soil. A
      hydrogen-using methanogen, strain TM-8, was isolated from flooded paddy field
      soil. Strain TM-8 was identified as Methanobacterium formicicum based on its
      physiology and phylogeny. Syntrophic butyrate-degrading bacteria were enumerated
      and isolated using strain TM-8. A syntrophic butyrate-degrading bacterium, strain
      TB-6, was isolated in coculture with strain TM-8 from paddy soil. The strain was
      Gram-negative, had curved rods, and grew on crotonate. Sulfate was not used as an
      electron acceptor. Strain TB-6 was closely related to S. wolfei subsp. wolfei.
      The relation between strain TB-6 and the members of Syntrophomonas are discussed.

PMID- 14586092
TI  - Isolation of GnafC, a polysaccharide constituent of Gnaphalium affine, and
      synergistic effects of GnafC and ascorbate on the phenotypic expression of
      osteoblastic MC3T3-E1 cells.
AB  - After screening extensively factors in plant extracts that increase alkaline
      phosphatase activity, an osteoblastic differentiation marker protein in mouse
      calvarial osteoblast MC3T3-E1 cells, GnafC derived from Gnaphalium affine, was
      found to significantly enhance the alkaline phosphatase (ALPase) activity in a
      synergistic manner with ascorbate. GnafC was a polysaccharaide with an
      approximate molecular mass of 10,000 and comprised mannose, xylose, arabinose,
      galactose and glucose in a molar ratio of 1:2:4.3:2.5:2.7. Expression of the
      osteoblastic differentiation marker genes was examined by semiquantitative RT-PCR
      with RNAs prepared from cells at different developmental stages. With ascorbate
      in the culture, GnafC enhanced the expression of the ALPase and MMP13 genes from
      the early stage of differentiation, leading to maturation of the collagenous
      extracellular matrix (ECM), a prerequisite for mineralization.

PMID- 14586093
TI  - Transformation of the white-rot basidiomycete Coriolus hirsutus using the
      ornithine carbamoyltransferase gene.
AB  - An efficient transformation system for the basidiomycete Coriolus hirsutus was
      developed. A double-auxotrophic mutant of C. hirsutus, deficient both in
      ornithine carbamoyltransferase (OCTase) and 3-isopropylmalate dehydrogenase (3
      IPM dehydrogenase), was transformed to Arg+ with each allelic type of the C.
      hirsutus genomic OCTase gene (arg1) newly cloned. The transformation frequency of
      10(3)-10(4) transformants per mug DNA per 10(6)-10(7) oidial protoplasts was
      reached. Southern blots showed that the transforming DNA was integrated into
      chromosomal DNA with multi-copies. The Arg+ phenotype of the transformants was
      stably inherited through mitosis.

PMID- 14586094
TI  - Attenuating effect of chlorella supplementation on oxidative stress and NFkappaB
      activation in peritoneal macrophages and liver of C57BL/6 mice fed on an
      atherogenic diet.
AB  - This study was designed to investigate whether chlorella supplementation may
      ameliorate oxidative stress and nuclear factor kappa B (NFkappaB) activation in
      peritoneal macrophages and liver of C57BL/6 mice fed on an atherogenic diet. The
      animals were maintained on an atherogenic diet (control), or an atherogenic diet
      supplemented with 3% (w/w) chlorella or 5% (w/w) chlorella for 12 wks. The plasma
      and hepatic lipid levels were not affected by chlorella supplementation. Hepatic
      thiobarbituric acid-reactive substances and superoxide anion production in
      peritoneal macrophages were significantly lower in the 5% chlorella group
      (p<0.05), but the glutathione level was not altered by chlorella supplementation.
      The hepatic antioxidative enzyme activities of Cu, Zn-superoxide dismutase and
      catalase were higher in the mice fed on the 5% chlorella diet (p<0.05). The
      plasma aspartate aminotransferase activity was lower in the mice fed on the
      chlorella-containing diets (p<0.05), whereas the alanine aminotransferase
      activity was not affected by chlorella supplementation. The NFkappaB nuclear
      binding activities of peritoneal macrophages and liver were significantly lower
      in the 5% chlorella groups (p<0.05). These results suggest that chlorella
      supplementation may attenuate oxidative stress by reducing reactive oxygen
      production and increasing antioxidative processes, thus suppressing inflammatory
      mediator activation in peritoneal macrophages and liver.

PMID- 14586095
TI  - Antimutagenic activity of flavonoids from Chrysanthemum morifolium.
AB  - A methanol extract from the flower heads of Chrysanthemum morifolium showed a
      suppressive effect on umu gene expression of the SOS response in Salmonella
      typhimurium TA1535/pSK1002 against the mutagen 2-(2-furyl)-3-(5-nitro-2
      furyl)acrylamide (furylfuramide). The methanol extract was re-extracted with
      hexane, chloroform, ethyl acetate, butanol, and water. The ethyl acetate fraction
      showed a suppressive effect. Suppressive compounds in the ethyl acetate fraction
      were isolated by silica gel column chromatography and identified as the
      flavonoids acacetin (1), apigenin (2), luteolin (3), and quercetin (4) by EI-MS,
      IR, and (1)H and 13C NMR spectroscopy. Compounds 1-4 suppressed the furylfuramide
      induced SOS response in the umu test. Compounds 1-4 suppressed 60.2, 75.7, 90.0,
      and 66.6% of the SOS-inducing activity at a concentration of 0.70 micromol/ml.
      The ID50 (50% inhibitory dose) values of 1-4 were 0.62, 0.55, 0.44, and 0.59
      micromol/ml. These compounds had the suppressive effects on umu gene expression
      of the SOS response against other mutagens, 4-nitroquinolin 1-oxide (4NQO) and N
      methyl-N'-nitro-N-nitrosoguanidine (MNNG), which do not require liver
      metabolizing enzymes. These compounds also showed the suppression of SOS-inducing
      activity against the other mutagens aflatoxin B1 (AfB1) and 3-amino-1,4-dimethyl
      5H-pyrido[4,3-b]indole (Trp-P-1), which require liver-metabolizing enzymes, and
      UV irradiation. In addition to the antimutagenic activities of these compounds
      against furylfuramide, Trp-P-1 and activated Trp-P-1 were also assayed by the
      Ames test using S. typhimurium TA100.

PMID- 14586096
TI  - Blood coagulation and fibrinolysis of rats fed fish oil: reduced coagulation
      factors especially involved in intrinsic pathway and increased activity of
      plasminogen activator inhibitor.
AB  - Differences in the coagulation and fibrinolytic system of rats fed a fish oil
      based diet (fish oil diet) and fed a soybean oil based diet (control diet) were
      determined. Concentrations of plasma lipids were depressed in rats fed the fish
      oil diet. Prothrombin time (PT) and activated partial thromboplastin time (APTT)
      of rats fed the fish oil diet were longer than for the rats fed the control diet.
      Fish oil intake lowered the activities of most of the blood coagulation factors,
      and strongly depressed the factors involved in the intrinsic pathway. Fish oil
      also affected the fibrinolysis of rats. Plasminogen activator inhibitor (PAI)
      activity was elevated in rats fed the fish oil diet. In this study, both blood
      coagulation and fibrinolysis were down-regulated by feeding the fish oil diet.

PMID- 14586097
TI  - Biosynthesis of branched-chain fatty acid in bacilli: FabD (malonyl-CoA:ACP
      transacylase) is not essential for in vitro biosynthesis of branched-chain fatty
      acids.
AB  - It was found that the partially purified beta-ketoacyl-ACP synthase of Bacillus
      insolitus did not require the addition of FabD (malonyl-CoA:ACP transacylase,
      MAT) for the activity assay. This study therefore examined the necessity of FabD
      protein for in vitro branched-chain fatty acid (BCFA) biosynthesis by crude fatty
      acid synthetases (FAS) of Bacilli. To discover the involvement of FabD in the
      BCFA biosynthesis, the protein was removed from the crude FAS by
      immunoprecipitation. The His-tag fusion protein FabD of Bacillus subtilis was
      expressed in Escherichia coli and used for the preparation of antibody. The
      rabbit antibody raised against the expressed fusion protein specifically
      recognized the FabD in the crude FAS of B. subtilis. Evaluation of the efficacy
      of the immunoprecipitation showed that a trace of FabD protein was present in the
      antibody-treated crude FAS. However, this complete removal of FabD from the crude
      FAS did not abolish its BCFA biosynthesis, but only reduced the level to 50-60%
      of the control level for acyl-CoA primer and to 80% for alpha-keto-beta
      methylvalerate primer. Furthermore, the FabD concentration did not necessarily
      correlate with the MAT specific activity in the enzyme fractions, suggesting the
      presence of another enzyme source of MAT activity. This study, therefore,
      suggests that FabD is not the sole enzyme source of MAT for in vitro BCFA
      biosynthesis, and implies the existence of a functional connection between fatty
      acid biosynthesis and another metabolic pathway.

PMID- 14586098
TI  - Purification and characterization of membrane-bound quinoprotein quinate
      dehydrogenase.
AB  - Several bacterial strains carrying quinoprotein quinate dehydrogenase (QDH) were
      screened through acetic acid bacteria and other bacteria. Strong enzyme activity
      was found in the membrane fraction of Gluconobacter melanogenus IFO 3294, G.
      oxydans IFO 3292, G. oxydans IFO 3244, and some strains of Acinetobacter
      calcoaceticus. Interestingly, in the membrane fraction of A. calcoaceticus AC3,
      which is unable to produce pyrroloquinoline quinone (PQQ), fairly large amounts
      of apo-QDH were formed, and were converted to holo-QDH only by the addition of
      PQQ. It was difficult to detach PQQ from the holo-QDH by EDTA treatment, and EDTA
      treatment with apo-QDH prior to PQQ addition gave no significant holo-QDH. For
      QDH purification, Gluconobacter strains were not suitable due to the presence of
      huge amounts of quinohemoprotein alcohol dehydrogenase (ADH) in the same
      membrane, which was co-solubilized with QDH and disturbed purification of QDH.
      Purification of holo-QDH was done with Acinetobacter sp. SA1 instead, which
      contained no ADH. Apo-QDH was purified from A. aclcoaceticus AC3. This is the
      first report dealing with QDH purification, and two different criteria of QDH
      purification were given. A combination of two steps using butyl-Toyopearl and
      hydroxyapatite columns gave a highly purified holo-QDH which was monodispersed
      and showed enough purity, though the specific activity did not increase as much
      as expected. When QDH purification was done with A. calcoaceticus AC3 in the
      absence of PQQ, purified apo-QDH appeared to be a dimer, which was converted to
      the monomer on addition of PQQ. Since QDH was highly hydrophobic, one-step
      chromatography on a DEAE-Sepharose column was tried. Purified holo-QDH of higher
      specific activity was obtained with a higher yield. The molecular mass of QDH was
      estimated to be 88 kDa. There was no characteristic absorption spectrum with the
      purified QDH except for a small bump around 420 nm. QDH oxidized only quinate and
      shikimate so far examined. The optimal QDH activity was found at pH 6-7 when
      assayed with artificial electron acceptors. QDH was formed in the presence or
      absence of quinate in the culture medium, although stronger induction was usually
      observed in the presence of quinate.

PMID- 14586099
TI  - 3-dehydroquinate production by oxidative fermentation and further conversion of 3
      dehydroquinate to the intermediates in the shikimate pathway.
AB  - 3-Dehydroquinate production from quinate by oxidative fermentation with
      Gluconobacter strains of acetic acid bacteria was analyzed for the first time. In
      the bacterial membrane, quinate dehydrogenase, a typical quinoprotein containing
      pyrroloquinoline quinone (PQQ) as the coenzyme, functions as the primary enzyme
      in quinate oxidation. Quinate was oxidized to 3-dehydroquinate with the final
      yield of almost 100% in earlier growth phase. Resting cells, dried cells, and
      immobilized cells or an immobilized membrane fraction of Gluconobacter strains
      were found to be useful biocatalysts for quinate oxidation. 3-Dehydroquinate was
      further converted to 3-dehydroshikimate with a reasonable yield by growing cells
      and also immobilized cells. Strong enzyme activities of 3-dehydroquinate
      dehydratase and NADP-dependent shikimate dehydrogenase were detected in the
      soluble fraction of the same organism and partially fractionated from each other.
      Since the shikimate pathway is remote from glucose in the metabolic pathway, the
      entrance into the shikimate pathway from quinate to 3-dehydroquinate looks
      advantageous to produce metabolic intermediates in the shikimate pathway.

PMID- 14586100
TI  - Endophytic colonization of balloon flower by antifungal strain Bacillus sp. CY22.
AB  - Endophytic Bacillus sp. CY22 was previously isolated from the root interior of
      the balloon flower (Platycodon grandiflorum) (Cho et al., Biosci. Biotechnol.
      Biochem., 66, 1270-1275 (2002)). Three-month-old balloon flower seedlings were
      inoculated with 10(7) cfu/ml of strain CY22R3, a rifampicin-resistant strain of
      CY22, and external and internal root colonization was assessed 2 and 4 weeks
      later. After inoculation, large numbers of bacteria were observed on the root
      surface by scanning electron microscopy. More detailed studies using optical and
      transmission electron microscopy confirmed that Bacillus sp. CY22 was
      endophytically established within intercellular spaces, cortical cells, and
      aerenchymas of root. Also, Bacillus sp. CY22 showed antibiotic activities against
      several phytopathogens by producing the antibiotic iturin A. In the pot test,
      root rot of balloon flower seedlings caused by Rhizoctonia solani was suppressed
      when the Bacillus sp. CY22R3 was inoculated into the soil.

PMID- 14586101
TI  - Purification of turkey pancreatic phospholipase A2.
AB  - Turkey pancreatic phospholipase (TPP) has been purified from delipidated
      pancreases. The purification included ammonium sulfate fractionation, acidic (pH
      5) treatment, followed by sequencial column chromatographies on DEAE-cellulose,
      Sephadex G-75, and reverse phase high pressure liquid chromatography. The
      purified enzyme was found to be a monomeric protein with molecular mass of 14
      kDa. The optimal activity was measured at pH 8 and 37 degrees C using egg yolk
      emulsion as substrate. Our results show that the enzyme (TPP) was not stable for
      1 h at 60 degrees C, and that bile salt and Ca2+ were required for the expression
      of the purified enzyme. The sequence of the N-terminal amino acids of the
      purified enzyme shows a very close similarity between TPP and all other known
      pancreatic phospholipases.

PMID- 14586102
TI  - Purification and characterization of an alpha-haloketone-resistant formate
      dehydrogenase from Thiobacillus sp. strain KNK65MA, and cloning of the gene.
AB  - Thiobacillus sp. strain KNK65MA, which produced an NAD-dependent formate
      dehydrogenase (FDH) highly resistant to alpha-haloketones, was newly isolated,
      i.e., the enzyme showed no loss of activity after a 5-h incubation with alpha
      haloketones, such as ethyl 4-chloro-3-oxobutanoate. The enzyme was also resistant
      to SH reagents. The enzyme, purified to homogeneity, was a dimer composed of
      identical subunits. The specific activity was 7.6 u/mg, and the apparent Km
      values for formate and NAD+ were 1.6 and 0.048 mM, respectively. The cloned gene
      of FDH contained one open reading frame (ORF) of 1206 base pairs, predicted to
      encode a polypeptide of 401 amino acids, with a calculated molecular weight of
      44,021; this gene was highly expressed in E. coli cells. The deduced amino acid
      sequence of this FDH had high identity to other bacterial FDHs.

PMID- 14586103
TI  - Purification and identification of antimicrobial sesquiterpene lactones from
      yacon (Smallanthus sonchifolius) leaves.
AB  - The extraction of yacon [Smallanthus sonchifolius (Poepp. and Endl.) H. Robinson;
      Asteraceae] leaves and chromatographic separation yielded two new antibacterial
      melampolide-type sesquiterpene lactones, 8beta-tigloyloxymelampolid-14-oic acid
      methyl ester and 8beta-methacryloyloxymelampolid-14-oic acid methyl ester, as
      well as the four known melampolides, sonchifolin, uvedalin, enhydrin and
      fluctuanin. The newly identified compound, 8beta-methacryloyloxymelampolid-14-oic
      acid methyl ester, exhibited potent antimicrobial activity against Bacillus
      subtilis and Pyricularia oryzae, while 8beta-tigloyloxymelampolid-14-oic acid
      methyl ester showed lower activity. Fluctuanin exhibited the strongest
      antibacterial activity against B. subtilis among these six sesquiterpene
      lactones.

PMID- 14586105
TI  - A thermostable laccase from Streptomyces lavendulae REN-7: purification,
      characterization, nucleotide sequence, and expression.
AB  - We found a polyphenoloxidase (PPO) in the cell extract of Streptomyces lavendulae
      REN-7. About 0.8 mg of purified PPO was obtained from 200 g of the mycelia with a
      yield of 9.0%. REN-7-PPO showed broad substrate specificity toward various
      aromatic compounds. Moreover, this enzyme was capable of oxidation of
      syringaldazine, which is a specific substrate for laccase. Interestingly, REN-7
      PPO retained its original activity after 20 min of incubation at even 70 degrees
      C. The gene encoding the PPO was cloned. Four copper-binding sites
      characteristics of laccases were contained in the deduced amino acid sequence. We
      constructed a high-level expression system of this gene in Escherichia coli. The
      properties of the recombinant enzyme were identical that of wild-type. In
      conclusion, this PPO is a thermostable laccase.

PMID- 14586104
TI  - Cloning, sequencing, and expression of the gene encoding the Clostridium
      stercorarium alpha-galactosidase Aga36A in Escherichia coli.
AB  - The alpha-galactosidase gene aga36A of Clostridium stercorarium F-9 was cloned,
      sequenced, and expressed in Escherichia coli. The aga36A gene consists of 2,208
      nucleotides encoding a protein of 736 amino acids with a predicted molecular
      weight of 84,786. Aga36A is an enzyme classified in family 36 of the glycoside
      hydrolases and showed sequence similarity with some enzymes of family 36 such as
      Geobacillus (formerly Bacillus) stearothermophilus GalA (57%) and AgaN (52%). The
      enzyme purified from a recombinant E. coli is optimally active at 70 degrees C
      and pH 6.0. The enzyme hydrolyzed raffinose and guar gum with specific activities
      of 3.0 U/mg and 0.46 U/mg for the respective substrates.

PMID- 14586106
TI  - Inhibition of immunoglobulin E production in allergic model mice by
      supplementation with vitamin E and beta-carotene.
AB  - A diet containing different amounts of vitamin E (alpha-tocopherol; 0.5 mg, 5 mg,
      10 mg or 50 mg per 100 g diet) was supplemented to BALB/c mice for 6 weeks. These
      mice were subcutaneously immunized twice with ovalbumin (OVA). A passive
      cutaneous anaphylaxis (PCA) analysis demonstrated that the mice fed on the diet
      containing 5 mg of vitamin E produced the highest level of the OVA-specific
      immunoglobulin E (IgE) antibody. A lower level of serum IgE was found in the mice
      supplemented with 0.5 mg, 10 mg and 50 mg of vitamin E. A sandwich ELISA analysis
      showed that the pattern of the total IgE antibody level among these four groups
      was the same as that of the allergen-specific IgE. In a separate experiment, 5 mg
      of vitamin E and/or 50 mg of beta-carotene was supplemented to the basal diet
      containing vitamin E as alpha-tocopherol acetate (5 mg) in order to evaluate the
      effect of their combination on OVA-specific and total IgE production in the mice.
      The supplementation with beta-carotene alone had no effect on OVA-specific or
      total IgE production. In contrast, supplementation with vitamin E plus beta
      carotene effectively suppressed both the antigen-specific and total IgE
      antibodies. The serum vitamin E and beta-carotene levels were increased by
      supplementation with the respective compounds. These results strongly suggest
      that the combination of dietary vitamin E and beta-carotene suppressed IgE
      production and would therefore help to prevent the type-I allergic reaction.

PMID- 14586107
TI  - Systematic strategy for the synthesis of cyanobacterin and its stereoisomers. 1.
      Asymmetric total synthesis of dechloro-cyanobacterin and its enantiomer.
AB  - The stereocontrolled total synthesis of the non-chlorinated analog of
      cyanobacterin, a potent photosynthesis inhibitor, was achieved by 12 steps in a
      10.0% overall yield. Its enantiomer was also synthesized from the same starting
      material. This synthetic strategy is expected to be applicable to prepare
      cyanobacterin and all its stereoisomers, together with other similar bioactive
      compounds.

PMID- 14586108
TI  - Mode of alpha-amylase production by the shochu koji mold Aspergillus kawachii.
AB  - Aspergillus kawachii produces two kinds of alpha-amylase, one is an acid-unstable
      alpha-amylase and the other is an acid-stable alpha-amylase. Because the quality
      of the shochu depends strongly on the activities of the alpha-amylases, the
      culture conditions under which these alpha-amylases are produced were examined.
      In liquid culture, acid-unstable alpha-amylase was produced abundantly, but, acid
      stable alpha-amylase was not produced. The acid-unstable alpha-amylase was
      produced significantly when glycerol or glucose was used as a carbon source,
      similarly to the use of inducers such as starch or maltose. In liquid culture, A.
      kawachii assimilated starch at pH 3.0, but no alpha-amylase activity was
      recognized in the medium. Instead, the alpha-amylase was found to be trapped in
      the cell wall. The trapped form was identified as acid-unstable alpha-amylase.
      Usually, acid-unstable alpha-amylase is unstable at pH 3.0, so its stability
      appeared to be due to its immobilization in the cell wall. In solid-state
      culture, both kinds of alpha-amylase were produced. The production of acid-stable
      alpha-amylase seems to be solid-state culture-specific and was affected by the
      moisture content in the solid medium.

PMID- 14586109
TI  - Efficient electrotransformation system and gene targeting in pyogenic
      streptococci.
AB  - Hemolytic streptococci are lacking in natural competence for uptake of DNA, and
      existing electrotransformation methods are still ineffective for most strains. By
      optimizing biological and electric parameters of electroporation, we established
      a simple, efficient, and reproducible transformation method for streptococcal
      cells. The major factor was an increase in the electric field strength. All
      tested streptococci (6 group A strains and one group C strain) were successfully
      transformed, and the maximal efficiency was higher than 1 x 10(7) transformants
      per mug of plasmid DNA. Targeted inactivation of the chromosomal genes of group A
      and C streptococci was achieved, using the electrotransformation method. The slo-
      or sagB- mutants constructed by the gene-targeting showed elevated competence for
      electrotransformation. Availability of the electrotransfer system for cloning and
      analysis of streptococcal genes is discussed.

PMID- 14586110
TI  - Synthesis of the racemate and both enantiomers of massoilactone.
AB  - A simple and efficient synthesis of (+/-)-massoilactone (1) as a key substance
      for the butter and milk flavor was accomplished from n-hexanal in only a few
      steps. Application of its racemic synthesis enabled natural (R)-(-)- and
      unnatural (S)-(+)-massoilactone (1a, 1b) to be synthesized by starting from
      commercially available (R)-(+)-1,2-epoxyheptane (5).

PMID- 14586111
TI  - Systematic strategy for the synthesis of cyanobacterin and its stereoisomers. 2.
      Asymmetric total synthesis of the 2- and 3-epimers of dechloro-cyanobacterin.
AB  - Stereocontrolled total syntheses of the (2S,3R)- and (2R,3S)-isomers of the non
      chlorinated analog of cyanobacterin, a potent photosynthesis inhibitor, were
      achieved. Since both the (2R,3R)- and (2S,3S)-isomers of this compound had been
      previously synthesized from the same starting material, a systematic strategy for
      the synthesis of all stereoisomers could be established.

PMID- 14586112
TI  - Synthesis of the enantiomers of 21-methyl-7-hentriacontanone and a stereoisomeric
      mixture of 5-acetoxy-19-methylnonacosane, candidates for the female sex pheromone
      of the screwworm fly Cochliomyia hominivorax.
AB  - The enantiomers of 21-methyl-7-hentriacontanone (1), which might show weak
      bioactivity as the female sex pheromone of the screwworm fly (Cochliomyia
      hominivorax), were synthesized by starting from the enantiomers of citronellal.
      (+/-)-Citronellol was converted to a racemic and diastereomeric mixture of 5
      acetoxy-19-methylnonacosane (2), which was considered to be a candidate for the
      female sex pheromone of C. hominivorax. Synthetic 2 exhibited no pheromone
      activity against male C. hominivorax.

PMID- 14586113
TI  - Structural features of N-glycans linked to glycoproteins from oil palm pollen, an
      allergenic pollen*.
AB  - The pollen of oil palm (Elaeis guineensis Jacq.) is a strong allergen and causes
      severe pollinosis in Malaysia and Singapore. In the previous study (Biosci.
      Biotechnol. Biochem., 64, 820-827 (2002)), from the oil palm pollens, we purified
      an antigenic glycoprotein (Ela g Bd 31 K), which is recognized by IgE from palm
      pollinosis patients. In this report, we describe the structural analysis of sugar
      chains linked to palm pollen glycoproteins to confirm the ubiquitous occurrence
      of antigenic N-glycans in the allergenic pollen. N-Glycans liberated from the
      pollen glycoprotein mixture by hydrazinolysis were labeled with 2-aminopyridine
      followed by purification with a combination of size-fractionation HPLC and
      reversed-phase HPLC. The structures of the PA-sugar chains were analyzed by a
      combination of two-dimensional sugar chain mapping, electrospray ionization mass
      spectrometry (ESI-MS), and tandem MS analysis, as well as exoglycosidase
      digestions. The antigenic N-glycan bearing alpha1-3 fucose and/or beta1-2 xylose
      residues accounts for 36.9% of total N-glycans: GlcNAc2Man3Xyl1Fuc1GlcNAc2
      (24.6%), GlcNAc2Man3Xyl1GlcNAc2 (4.4%), Man3Xyl1Fuc1-GlcNAc2 (1.1%),
      GlcNAc1Man3Xyl1Fuc1GlcNAc2 (5.6%), and GlcNAc1Man3Xyl1GlcNAc2 (1.2%). The
      remaining 63.1% of the total N-glycans belong to the high-mannose type structure:
      Man9GlcNAc2 (5.8%), Man8GlcNAc2 (32.1%), Man7GlcNAc2 (19.9%), Man6GlcNAc2 (5.3%).

PMID- 14586114
TI  - Synthesis and absolute configuration of (-)-3-butyl-7-hydroxyphthalide, a
      cytotoxic metabolite of Penicillium vulpinum.
AB  - Both the enantiomers as well as the racemate of 3-butyl-7-hydroxyphthalide (1)
      were synthesized, and the absolute configuration of the naturally occurring (-)-1
      (a weakly cytotoxic metabolite of Penicillium vulpinum) was identified as S.

PMID- 14586115
TI  - Expression profiling of translation-associated genes in sporulating Bacillus
      subtilis and consequence of sporulation by gene inactivation.
AB  - A DNA microarray technique was used to demonstrate global changes in the
      transcription pattern of translation-associated genes that encode fifty-four
      ribosomal proteins including a putative ribosomal gene, and eleven translation
      factors in sporulating B. subtilis. We found that the mRNA levels of nine genes
      involved in the translation system, which include the genes for three ribosomal
      proteins (rpmA, rpmGB, and ctc) and two translation factors (efp, and frr), were
      maintained at a high level at the onset of sporulation. The ypfD gene, which
      encodes the ribosomal protein S1 homologue, was also found to be expressed
      significantly during the early sporulation stage. In order to demonstrate the
      significance of these genes for sporulation, mutants were constructed using the
      pMutinT3 disruption vector. We detected an impaired sporulation in the mutants of
      rpmA (gene for the ribosomal protein L27), efp (elongation factor P), frr
      (ribosome recycling factor), and ypfD. The effect was especially pronounced in
      the efp mutant, sporulation of which was entirely abolished without affecting
      growth. The reduced expression of rpmGB (ribosomal protein L33) resulted in an
      impaired sporulation only at a high temperature (47 degrees C). Only the rplI
      mutant, which encodes the ribosomal protein L9, could not be obtained, implying
      that its function is essential for viability. Thus, we successfully demonstrated
      the significance of several translation-associated genes in sporulation by using
      the results of the gene expression profiling.

PMID- 14586116
TI  - Expression and characterization of bovine lactoperoxidase by recombinant
      baculovirus.
AB  - Lactoperoxidase (LPO) is a heme-containing oxidation-reduction enzyme present in
      milk. In this study, the gene encoding bovine lactoperoxidase (bLPO) was inserted
      into a baculovirus transfer vector, and a recombinant virus expressing bLPO was
      isolated. A bLPO-related recombinant baculovirus-expressed protein of 78 kDa was
      detected using anti-bLPO antibodies. After digestion with N-glycosidase F, the
      molecular weight of the recombinant bLPO (rbLPO) decreased. In addition, rbLPO
      reacted with lectin, indicating that the protein was glycosylated. The rbLPO
      activity and heme content in the culture supernatants increased upon addition of
      delta-aminolevulinic acid, which is a heme precursor. Differences in the delta
      aminolevulinic acid-dependent circular dichroism spectrum and rbLPO pepsin
      hydrolysis were observed. These results suggest that the secondary structure and
      structural stability of rbLPO depends on the heme environment. Our data suggest
      that this bLPO expression system is useful for studying structure, catalytic
      mechanisms, and biological function.

PMID- 14586117
TI  - Differential expression of the nonmuscle-type cofilin gene between subcutaneous
      and visceral adipose tissue.
AB  - Visceral adipocytes differ in various biochemical properties from adipocytes of
      subcutaneous origin. However, information on differences in gene expression
      between visceral and subcutaneous fat depots is limited. Expression of the genes
      for the nonmuscle and muscle isoforms of the actin-binding protein cofilin was
      examined in subcutaneous and visceral fat depots of mice, pigs, and cattle by
      semiquantative reverse transcription and polymerase chain reaction analysis. The
      abundance of nonmuscle-type cofilin mRNA was markedly higher in visceral adipose
      tissue than in subcutaneous adipose tissue of mouse and pig. This difference was
      more pronounced in mice fed a high-fat diet than in those fed a standard diet. In
      cattle, however, the amount of nonmuscle-type cofilin mRNA was greater in
      subcutaneous fat than in visceral fat. Muscle-type cofilin mRNA was not detected
      in either adipose tissue of any of the three species. These results suggest that
      the nonmuscle isoform of cofilin, and therefore the cytoskeleton, may play a role
      in lipid accumulation in visceral adipose tissue.

PMID- 14586118
TI  - Effects of the marine unicellular alga Nannochloropsis sp. to reduce the plasma
      and liver cholesterol levels in male rats fed on diets with cholesterol.
AB  - The effects of Nannochloropsis were studied on rats consuming
      hypercholesterolemic diets. The whole biomass and the hexane/ethanol extract
      increased the plasma and hepatic eicosapentaenoic and docosahexaenoic acids
      levels, and reduced the cholesterol levels. We also observed a higher level of
      propionate, and a lower ratio between acetate and propionate. These data suggest
      the efficacy of Nannochloropsis in reducing cholesterol levels.

PMID- 14586119
TI  - Effect of alpha,alpha-dialkyl amino acids on the protease resistance of peptides.
AB  - A tryptic [EC 3.4.21.4] digestion assay of 2-aminoisobutyric acid (Aib)
      containing peptides was carried out to investigate the effect of alpha,alpha
      dialkyl amino acid residues on the protease resistance. The introduction of Aib
      residues to the P1' positions exhibited a 19-fold higher protease resistance than
      the peptide with Aib residues introduced to the P2 position or the non-Aib
      peptide. The peptide having Aib residues introduced to the P1' and P2 positions
      resulted in complete resistance.

PMID- 14586120
TI  - PEG-inhibitor conjugates: application of diphenyl alpha-aminoalkylphosphonate to
      removal of chymotrypsin.
AB  - Diphenyl 1-amino-2-phenylethylphosphonate was introduced to poly(ethylene
      glycol)s (PEGs) with average molecular masses of 300, 400, and 600 to prepare
      water-insoluble PEG-inhibitor conjugates. Interestingly, only the conjugate from
      PEG with an average molecular weight of 600 formed a precipitate with
      chymotrypsin but not with trypsin. The results demonstrated that the PEG
      inhibitor conjugate is useful for separation of chymotrypsin.

PMID- 14586121
TI  - Production of functional lectin in Pichia pastoris directed by cloned cDNA from
      Aleuria aurantia.
AB  - A plasmid bearing a nucleotide sequence of fucose-specific lectin of Aleuria
      aurantia was constructed and expressed in a methylotrophic yeast, Pichia
      pastoris. The product showed almost the same hemagglutinating activity as the
      lectin produced in Escherichia coli, the properties of which were quite similar
      to the native one. Because of glycosylation of the product, the molecular mass
      was larger than that of the native one, and it acquired higher thermostability.

PMID- 14586122
TI  - Linoleic acid 10-hydroperoxide as an intermediate during formation of 1-octen-3
      ol from linoleic acid in Lentinus decadetes.
AB  - In order to confirm the biosynthetic pathway to 1-octen-3-ol from linoleic acid,
      a crude enzyme solution was prepared from the edible mushroom, Lentinus
      decadetes. When the reaction was performed in the presence of glutathione
      peroxidase, which can reduce organic hydroperoxide to the corresponding
      hydroxide, the amount of 1-octen-3-ol formed from linoleic acid was decreased. At
      the same time, an accumulation of linoleic acid 10-hydroxide could be detected.
      The 10-hydroperoxide therefore seems to be an intermediate on the biosynthetic
      pathway.

PMID- 14586123
TI  - Acivicin induce filamentous growth of Saccharomyces cerevisiae.
AB  - The antibiotic acivicin is a known inhibitor of gamma-glutamyl transpeptidase
      (gammaGTP). We found that acivicin can induce filamentous growth in both diploid
      and haploid cells of Saccharomyces cerevisiae. This phenomenon is not related to
      the inhibition of gammaGTP or interference in glutathione metabolism.
      Interestingly, yeasts used in the brewing industry are more sensitive to
      acivicin, suggesting that this dimorphological differentiation may be related to
      some characteristics of these particular strains.

PMID- 14586124
TI  - Isolation and characterization of a stilbene-degrading strain of Pseudomonas
      fluorescens, and production of antioxidant compounds by stilbene metabolism.
AB  - In this study, we consider the use of hydrocarbon-degrading bacteria that degrade
      trans-stilbene as a novel approach for synthesizing potentially bioactive
      hydroxylated stilbenes. A trans-stilbene-degrading bacterium, MN2, was isolated
      from activated sludge through enrichment culture, and identified as Pseudomonas
      fluorescens using conventional techniques. Degradation of trans-stilbene by this
      strain yielded two metabolites that had significant antioxidant activity.

PMID- 14586125
TI  - Efficient production of recombinant human pleiotrophin in yeast, Pichia pastoris.
AB  - Approximately 260 mg/l of authentic recombinant human pleiotrophin (rhPTN) was
      expressed into the medium of high-cell density fermentation using a Pichia
      pastoris protein expression system. The prepro-sequence of yeast alpha-mating
      factor was used successfully. The recombinant hPTN was efficiently recovered from
      the medium by expanded bed adsorption, and purified using successive column
      chromatography steps. In the purified rhPTN preparation, modified rhPTN were
      scarcely detected. Circular dichroism measurement of the purified PTN showed the
      presence of the characteristic beta-structures in the protein.

PMID- 14586126
TI  - Addition of a peptide tag at the C terminus of AtHKT1 inhibits its Na+ transport.
AB  - Eight transmembrane segments in the Arabidopsis Na+ transporter, AtHKT1, have
      been proposed to be arranged around the axis of the pore. We report here that the
      addition of a GFP or a FLAG tag to the C terminus of AtHKT1 impairs the Na+
      transport in Xenopus ooytes as detected by electrophysiological measurements.

PMID- 14586127
TI  - The protein component of bacterial ribonuclease P flickers the metal ion response
      to the substrate shape preference of the ribozyme.
AB  - The substrate shape specificity of the Escherichia coli ribonuclease P (RNase P)
      ribozyme depends on the concentration of magnesium ion. At 10 mM or more, it can
      cleave a hairpin substrate as well as a cloverleaf pre-transfer RNA (tRNA). The
      results showed, however, that the holo enzyme cleaved the hairpin substrate at
      low concentrations of magnesium ion. Considering that the homologous E. coli
      tRNAs are resistant to internal cleavage by the RNase P, the phenomena suggest
      that this catalytic activity might take part in the removing the mis-folded RNAs
      in the cell.

PMID- 14586128
TI  - Modulations of food-derived substances on intestinal permeability in Caco-2 cell
      monolayers.
AB  - The effects of more than 300 kinds of food extracts on intestinal permeability
      were investigated in Caco-2 cells with the use of model compounds: Lucifer Yellow
      (LY) for the paracellular pathway, Fluorescein (FC) for the monocarboxylic acid
      transporter-mediated pathway, and Rhodamine 123 (RH) for the p-glycoprotein
      mediated efflux pathway. With several extracts of increasing or decreasing LY
      permeation, increasing FC or RH permeation was also observed, indicating
      modulation by dietary substances in several pathways for intestinal absorption.

PMID- 14586129
TI  - A novel gene encoding an enzyme that degrades a polysaccharide from the sheath of
      Sphaerotilus natans.
AB  - A gene encoding an enzyme that is able to depolymerize the basic polysaccharide
      prepared from the sheath of Sphaerotilus natans was identified in a sheath
      degrading bacterium, Paenibacillus koleovorans. The gene was constructed from
      2217 bp coding for 738 amino acids, including the signal sequence of 34 amino
      acids. No closely related protein or gene was indicated by a homology search. The
      gene was expressed in Escherichia coli as a glutathione S-transferase fusion
      protein. The fusion protein depolymerized the sheath polysaccharide into an
      oligosaccharide, introducing an unsaturated sugar residue, suggesting that the
      gene codes for a polysaccharide lyase acting on a basic polysaccharide.

PMID- 14586130
TI  - Increased production of antioxidative sesaminol glucosides from sesame oil cake
      through fermentation by Bacillus circulans strain YUS-2.
AB  - Bacillus circulans strain YUS-2 was isolated as the strongest antioxidant
      producer in fermentation of sesame oil cake (SOC, defatted residue yielded from
      sesame seed oil production). Two major strong antioxidants from fermented SOC
      were purified and identified as known sesaminol triglucoside and sesaminol
      diglucoside, however, our results demonstrated that the fermentation process with
      B. circulans YUS-2 was highly effective to gain the extraction efficiency of the
      sesaminol glucosides.

PMID- 14586131
TI  - A new type of RNase T2 ribonuclease in two Basidiomycetes fungi, Lentinus edodes
      and Irpex lacteus.
AB  - Two new RNase T2 Ribonucleases, RNase Le37 and Irp3, with a molecular mass of 45
      kDa, have been isolated from Basidiomycetes fungi, Lentinus edodes and Irpex
      lacteus, respectively. The ribonucleases consisted of three domains: an RNase
      active domain, a Ser/Thr rich domain similar to that of many fungal
      glycanhydrolases, and a C-terminal 10 kDa domain similar to that of RNase Rny1 in
      yeast. The locations of hydrophobic amino acids and Pro in the 10 kDa domain of
      the two basidiomycetous enzymes are very similar to those of RNase Rny1,
      indicating that these domains may have similar roles.

PMID- 14586132
TI  - The discovery of the matrix cell, the identification of the multipotent neural
      stem cell and the development of the central nervous system.
AB  - In the early 1960s I applied 3H-thymidine autoradiography to the study of the
      cells constituting the neural tube, and found that its wall was composed solely
      of one kind of single-layered epithelial cell, which perform an elevator movement
      between the mitotic and DNA-synthetic zones in the wall in accord with the cell
      cycle. They were identified as multipotent stem cells of the central nervous
      sytem (CNS) to which I gave the name of matrix cells. (3)H-thymidine
      autoradiography also revealed the chronology of development of these matrix
      cells: At first they proliferate only to expand the population (stage I), then
      switch to differentiate specific neuroblasts in given sequences (stage II), and
      finally change themselves into ependymoglioblasts, common progenitors of
      ependymal cells and neuroglia (stage III). Based on these findings, I proposed a
      monophyletic view of cytogenesis of the central nervous sytem. This matrix cell
      theory claiming the existence of multipotent stem cells has long been the target
      of severe criticism and not been accepted among neuro-embryologists for a long
      time. Recent findings by experimental and clinical neuroscientists on the
      importance of stem cells have renewed interest in the nature and biology of the
      multipotent neural stem cells. The present paper describes how the concept of the
      matrix cell (multipotent neural stem cells in vivo) emerged and what has come out
      from this view over the last 45 years, and how the basic concept of the matrix
      cell theory has recently been reconfirmed after a long period of controversy and
      neglect.

PMID- 14586133
TI  - Spike formation by fibroblasts adhering to fibrillar collagen I gel.
AB  - The fibrillar collagen I gel induced the formation of numerous dendritic cell
      like protrusions (cell spikes) from the cell body, whereas monomeric collagen I
      induced typical cell spreading with filopodia and lamellipodia in skin
      fibroblasts. Peripheral, not central stress fibers appeared upon adhesion to
      fibrillar collagen gel, whereas both types of fibers were evident upon adhesion
      to monomeric collagen. Microtubules and vimentin filaments were elongated inside
      stress fibers along the terminal tip of cell spikes. Spike formation was totally
      inhibited by nocodazole and severely delayed by cytochalasin D. This suggests
      that cell spike formation is dependent on microtubules rather than on F-actin. We
      then investigated the intracellular signaling responsible for cytoskeleton
      organization to identify the key factor that induces cell spike morphology.
      During cell spike formation, FAK and CAS were activated. More CAS was activated
      in cells on fibrillar collagen gel than on the monomeric form, whereas FAK was
      activated to the same level on either. At 90 min of culture, Rac1 was activated
      in cells on monomeric collagen I, whereas Cdc42, Rac1 and RhoA were activated in
      cells on fibrillar collagen gel. These results suggest that microtubule
      organization via CAS and small GTPases is important for the cell spike formation
      that is involved in collagen gel contraction and in wound retraction in skin.

PMID- 14586134
TI  - Inhibition of Mg2+-dependent adhesion of polymorphonuclear leukocytes by serum
      hemopexin: differences in divalent-cation dependency of cell adhesion in the
      presence and absence of serum.
AB  - Circulating and nonadherent polymorphonuclear leukocytes (PMNs) become activated
      to attain adhesive state in an integrin-dependent manner by various stimuli, and
      perform a variety of microbicidal functions such as phagocytosis and superoxide
      production. We found that, in the absence of serum, a physiological concentration
      of hemopexin has a strong inhibitory action on Mg(2+)-dependent adhesion of PMA
      activated PMNs to fibrinogen- and serum-coated surfaces. Under these conditions,
      Ca(2+) had no effect on Mg(2+)-dependent adhesion or the adhesion-inhibitory
      activity of hemopexin. In contrast, PMNs suspended in serum containing sufficient
      amounts of hemopexin to inhibit adhesion showed marked adherence, which was
      inhibited by EGTA. Next, we prepared a small-molecule fraction of serum by
      ultrafiltration followed by boiling. PMA-activated PMNs was found to adhere in
      the presence of both hemopexin and the small-molecule fraction, and the adhesion
      was enhanced by exogenous Ca(2+). EGTA abolished the effect of the small molecule
      fraction. The data suggest that serum contains adhesion-promoting factor(s) which
      allows PMNs to adhere despite the presence of hemopexin and that Ca(2+) is
      required for adhesion-promoting activity. Further study of hemopexin may provide
      clues for new therapeutic strategies aimed at interfering with PMN adhesion to
      control inflammation and tissue injury.

PMID- 14586136
TI  - Advances in intraocular lens materials and designs: maximizing biocompatibility
      and optical performance.

PMID- 14586135
TI  - IGF-1 induces growth, survival and morphological change of primary hepatocytes on
      a galactose-bared polymer through both MAPK and beta-catenin pathways.
AB  - PVLA poly-(N-p-vinylbenzyl-O-beta-D-galactopyranosyl-D-gluconamide) is a
      glycopolymer composed of hydrophilic carbohydrate side chain and hydrophobic
      styrene polymer. The hydrophilic carbohydrate residue of PVLA can be recognized
      as a ligand for hepatocytes asialoglycoprotein receptor (ASGP-R), which is
      abundant on the hepatocyte cell surface. Adhering to the PVLA coated dishes,
      hepatocytes try to form aggregates that have a long time survival and also cells
      in these aggregates exhibit better maintenance of specific hepatocyte functions.
      Stimulation of the cells with IGF-1 in this culture condition results in the
      formation of lower aggregates. In addition to the morphological influences of IGF
      1 to these cells, we have also found that IGF-1 transmits growth stimulatory
      responses to hepatocytes on PVLA through both mitogen activated protein kinase
      (MAPK) pathway and beta-catenin pathways. The phosphorylation of MAPK can take
      place within 5 min of stimulation with IGF-1 and within at least 10 ng/ml of IGF
      1 concentration. Inhibition of MAPK activation by MEK-1 inhibitor PD98059 reduces
      IGF-1 induced MAPK phosphorylation, and also IGF-1 stimulated DNA synthesis.
      Similarly, the use of PI3-K inhibitor LY294002 also inhibits IGF-1 stimulated DNA
      synthesis. IGF-1 stimulation enhances the migration of beta-catenin from the
      cytoskeleton and cell membrane to the cytoplasm which also is the reason behind
      formation of spheroids and lower aggregates. IGF-1 stimulation also shows
      increased translocalization of beta-catenin to the nucleus that is essentially
      important to produce beta-catenin responsive effects to the cells. These studies
      thus suggest that IGF-1 can stimulate the growth and survival of hepatocytes on
      PVLA through both MAPK and beta-catenin signaling pathways, and that the
      activation of beta-catenin signaling pathway produces the morphological changes
      of IGF-1 induced cells.

PMID- 14586137
TI  - Regenerative medicine and vascular biology.

PMID- 14586138
TI  - Latest advances in refractive surgery.

PMID- 14586139
TI  - Pharmacology of ifosfamide.
AB  - Ifosfamide is a bifunctional alkylating agent, used as a racemic mixture by
      intravenous route in the treatment of various tumors. It is an oxazaphosphorine
      derivative with a structural formula similar to that of cyclophosphamide. As a
      prodrug it requires activation in the liver by a cytochrome mixed-function
      oxidase system. Among various metabolites, ifosforamide mustard probably
      represents the most important cytotoxic compound able to produce irreparable
      cross-links between DNA strands. Resistance is due to the ability of neoplastic
      cells to repair DNA damages. Acrolein may induce hemorrhagic cystitis, whereas
      chloroacetaldehyde may be responsible both for nephro- and neurotoxicity. A thiol
      donor (mesna) can prevent urotoxic effects but not nephro- and neurotoxicity.
      Pharmacokinetics is markedly influenced by route of administration and duration
      of treatment, age, co-medication, liver and renal function.

PMID- 14586140
TI  - Side effects of ifosfamide.
AB  - Ifosfamide is relatively well tolerated but it can be associated occasionally
      with life-threatening complications such as arrhythmias and heart failure, severe
      encephalopathy and hemorrhagic cystitis. Mesna administration can control the
      urothelial toxicity of ifosfamide, but it is without effect on the other
      complications. Other preventive measures, such as amifostine or methylene blue
      administration, have not yet been adequately evaluated in a sufficient number of
      patients. Clinicians prescribing ifosfamide, especially in high doses, should be
      watchful for early signs of toxicity in order to discontinue ifosfamide
      administration soon enough to avoid development of major toxicity.

PMID- 14586141
TI  - Neurological toxicity of ifosfamide.
AB  - Ifosfamide is an alkylating agent with well-demonstrated efficacy against a large
      number of malignant diseases. With cyclophosphamide it shares a toxicity profile
      characterized by myelosuppression and urotoxicity, but ifosfamide has
      additionally disclosed adverse neurological effects. Ifosfamide-related central
      nervous system toxicity is characterized by metabolic encephalopathy of varying
      severity. Symptoms have been reported in 5-30% of all patients treated with
      ifosfamide. The mechanism of ifosfamide-related central nervous system toxicity
      has not been fully elucidated, although the symptoms have most often been noted
      when the drug is given at high doses or administered orally. The neurotoxicity is
      generally self-limiting and reversible between 48 and 72 h after discontinuation
      of ifosfamide, although fatal sequelae have been reported. Therapeutic options
      are now available.

PMID- 14586142
TI  - Ifosfamide and cyclophosphamide: effects on immunosurveillance.
AB  - Ifosfamide (IF) and cyclophosphamide (CTX) are chemotherapeutic agents frequently
      used in the treatment of human malignancies. These drugs can exhibit a bimodal
      mechanism of antitumor action with cytotoxic and immunomodulatory effects when
      associated with adoptive immunotherapy. In human peripheral blood lymphocytes, IF
      irreversibly inhibits the proliferative response to interleukin-2 in a dose
      dependent manner and may also induce the phosphorylation of HSP27 by depleting
      glutathione. CTX promotes discrete cytokine profiles upregulating the expansion
      of Th1 cells, and this may be important to increase cellular immune response. The
      data presented in this report indicate that treatment regimens of CTX and IF may
      be used according to the tumor immunogenicity.

PMID- 14586143
TI  - Antiblastic drug combinations with ifosfamide: an update.
AB  - Ifosfamide is an alkylating agent that is widely used in the treatment of various
      neoplasms, such as sarcomas, lymphomas, pediatric malignancies, germ cell tumors,
      lung, breast and ovarian cancer. The clinical toxicity of ifosfamide depends on
      the dose and administration schedules. The pharmacologic features of this drug
      enable its combination with other antiblastic agents, such as vinorelbine,
      gemcitabine, paclitaxel and docetaxel. Moreover, the pharmacologic profile of
      ifosfamide allows the use of this antiblastic drug in patients who have
      previously failed many other treatments, and a large percentage of responses has
      already been obtained. There is some concern about the optimal scheduling of the
      drug with other novel chemotherapeutics. Clinical trials that include
      pharmacokinetic and pharmacodynamic studies may be the most efficient way to
      optimize the therapeutic efficacy of ifosfamide and define the dosing and
      scheduling.

PMID- 14586144
TI  - Dose finding of ifosfamide administered with a chronic two-week continuous
      infusion.
AB  - PURPOSE: Ifosfamide (IFO) is an active drug in several malignancies. A short-term
      3- to 7-day (A) continuous infusion (c.i.) has been used in different tumor
      types. The 14-day c.i. (B) has been investigated in advanced breast cancer and in
      soft tissue sarcoma patients at a fixed daily dose. The tolerance and response
      rate (RR) of therapies A and B has been considered encouraging. AIM: To study the
      14-day c.i. IFO schedule, every 28 days, with a dose-finding approach. METHODS:
      From January 1998 to December 2001, 34 pretreated patients with advanced
      malignancy and disease progression were treated with c.i. IFO (and the same dose
      of mesna) from 400 to 1,000 mg/m(2)/24 h for 2 consecutive weeks every 28 days.
      An elastomeric pumping device via an Infuse-a-Port((R)) or a Groshong((R))
      catheter was used. RESULTS: A total of 159 cycles were evaluable for toxicity and
      results. No toxic deaths occurred. Three patients (8.8%) had a severe acute
      allergic cutaneous reaction with various grade 3-4 toxicities requiring
      hospitalization and therapy was stopped at day 6 of the first cycle, 7 and 12 of
      the second cycle respectively. In the other 31 patients, grade 4 neutropenia
      occurred in 6 (19.3%) and it represented the main toxicity. There was a positive
      relationship between the IFO dose step and neutropenia (p = 0.001). A positive
      relationship was observed between the RR and the received total IFO dose (g) (p <
      0.004). Twelve patients out of 31 had progressive disease (PD) (38.7%), 8 had
      partial remission (PR) (25.8%), and 11 maintained a steady state (35.5%). Six of
      the 12 patients (50%) with PD and 2 of the 8 PRs (25%) had bone metastases.
      CONCLUSIONS: IFO c.i. is generally well tolerated, but acute untoward allergic
      reactions can occur. In chemotherapy-pretreated patients the recommended daily
      dose of continuously infused IFO for 14 days every 4 weeks is 900 mg/m(2)/day,
      together with mesna at the same dose schedule.

PMID- 14586145
TI  - Ifosfamide in the treatment of head and neck cancer.
AB  - Ifosfamide (IFO) has demonstrated activity in recurrent/metastatic squamous cell
      head and neck carcinoma with an overall response rate of 24-26%. Better results
      are reported for chemotherapy-naive patients; in heavily pretreated cases results
      are poor and toxicity unacceptable. Cisplatin-IFO combination in stage III-IV is
      probably more active than IFO alone (ORR = 60-72 vs. 50%) but is indicated in
      patients who desire aggressive treatment and are physically able to tolerate the
      drugs. The carboplatin-IFO scheme is better tolerated than the cisplatin-IFO
      regimen with superimposable clinical results (ORR = 69%; CR = 15%). Carboplatin
      taxol-IFO is one of the most active regimens in recurrent (ORR = 59%; CR = 17%)
      and in locally advanced (ORR = 81%; CR = 31%) head and neck cancer. Its role in
      the multidisciplinary treatment of advanced head and neck cancer is under
      investigation. In recurrent/metastatic undifferentiated nasopharygeal carcinoma,
      IFO combinations have proven to be effective as first- and second-line treatment.

PMID- 14586146
TI  - Ifosfamide in thymic neoplasms.
AB  - The role of systemic chemotherapy and optimal regimen in thymic neoplasms remains
      uncertain, because they are rare mediastinal tumors, frequently encapsulated or
      noninvasive at the time of presentation and surgical excision is adequate
      treatment. Chemotherapy is an essential treatment modality in advanced or
      recurrent disease and an increased number of publications on this aspect of
      management has appeared in the last 10 years. Both single-agent and combination
      chemotherapy have demonstrated activity in the adjuvant and neoadjuvant settings.
      There are little data concerning the activity of ifosfamide in thymoma and
      further investigation of the role of this drug in combination chemotherapy
      regimens, particularly as an alternative to the inclusion of cyclophosphamide, is
      warranted.

PMID- 14586147
TI  - Ifosfamide in small cell lung cancer.
AB  - Recent literature about the treatment options of small cell lung cancer stresses
      the role of ifosfamide both alone and in combination with either cisplatin or
      carboplatin and etoposide. Its pharmacokinetics and the lower hematological
      toxicity permit the use of high doses which seem to be more effective in this
      very sensitive tumor. However, despite the increment in the response rate, in
      both limited and extended disease, the overall and long-term survival seems to be
      little influenced by therapy. Newer strategies combining old and new therapeutic
      approaches have to be explored to overcome the lack of progresses registered in
      these years.

PMID- 14586148
TI  - Ifosfamide in non-small cell lung cancer.
AB  - In recent years the role of chemotherapy in advanced non-small cell lung cancer
      (NSCLC) has been well established. Ifosfamide is an old drug still considered an
      effective cytostatic agent in the treatment of NSCLC. As a single agent, it has
      showed a response rate of 20-25%. These results are improved when it is used in
      combination with cisplatin and mitomycin C. Moreover, in recent years, several
      new drugs like gemcitabine, taxanes and vinorelbine have been identified, and
      combinations of two or three drugs have been tested in patients with advanced
      NSCLC. This paper reviews the main studies recently conducted for the treatment
      of NSCLC, considering the results obtained by ifosfamide alone and in
      combination. Three-drug regimens including first-generation cytostatic agents
      achieve a response rate of about 40% and median survival of 10 months. In
      combinations with new drugs, ifosfamide shows an improvement in response rate
      (50%) with a median survival of more than 1 year. Open questions in the treatment
      of NSCLC are whether three-drug are better than two-drug combinations, and
      whether cisplatin is still required.

PMID- 14586149
TI  - Ifosfamide in advanced/disseminated breast cancer.
AB  - Ifosfamide is an alkylating agent active in various tumor types including breast
      cancer. The availability of mesna (sodium 2-mercaptoethanesulfonate) has
      increased its safety, avoiding the main dose-limiting side effect, urotoxicity.
      Interesting activity as a single agent, with response rates ranging from 7 to
      30%, is reported in pretreated patients; more attractive data derived from phase
      II studies on ifosfamide combined with drugs known to be active in advanced
      breast cancer show response rates always over 35%. This review has taken in
      consideration papers published after 1995 and available on PubMed medline: the
      data indicate a potential usefulness of ifosfamide in the clinical management of
      advanced breast cancer, even if the exact therapeutic role of the drug in this
      setting should be derived from randomized studies not yet available.

PMID- 14586150
TI  - Ifosfamide in the treatment of malignant epithelial ovarian tumors.
AB  - Ifosfamide is one of the best-known alkylating agents. In advanced epithelial
      ovarian cancer, it has been tested in association with cisplatin, achieving
      results equal, if not better than cyclophosphamide, with acceptable toxicity. In
      second-line therapy, it shows remarkable activity, even in patients refractory to
      cisplatin already treated with cyclophosphamide, with more severe, but always
      manageable toxicity. In gynecological sarcomas, ifosfamide is, together with
      doxorubicin, the reference drug for chemotherapy.

PMID- 14586151
TI  - Role of ifosfamide in cervical cancer: an overview.
AB  - Ifosfamide, a cyclophosphamide analogue, has demonstrated a wide spectrum of
      activity against numerous neoplasms in different oncologic areas, including
      paediatric, haematological, breast, lung and testicular cancers, soft tissue
      sarcomas and gynaecological cancer. In gynaecologic cancers in particular,
      evidence suggests activity in the treatment of epithelial ovarian cancer,
      cervical carcinoma, germ cell carcinoma of the ovary. Cervical cancer has long
      been considered a poorly chemosensitive tumour and for several years the role of
      chemotherapy in the treatment of this tumour was confined to persistent or
      recurrent disease after failure of surgery and/or radiotherapy. In the management
      of cervical cancer, chemotherapy has received increasing attention in the last
      two decades and is currently used in neoadjuvant regimens, as salvage treatment
      in patients with disseminated or recurrent disease, or as a radiosensitizer. Over
      the past 30 years, several agents have been tested but cisplatin and ifosfamide
      are the agents that have attracted the greater attention. Cisplatin represents
      the cornerstone of chemotherapy for cervical cancer. Ifosfamide has been studied
      as a single agent or in combination with other drugs in different studies. In
      this paper we reviewed the approach with systemic therapy and, in particular, the
      role of ifosfamide in advanced or recurrent, and less advanced cervical cancer.

PMID- 14586152
TI  - Ifosfamide in urologic cancer.
AB  - The therapeutic activity of ifosfamide in urologic tumors has been reviewed.
      Ifosfamide has definite activity in nephroblastoma, where it represents the
      treatment of choice for children who are not cured by front-line chemotherapy,
      and for the adults who are diagnosed with this uncommon disease. Definite
      therapeutic activity has also been shown in patients with urothelial tract
      malignancies and it represents a major option for patients failing first-line
      cisplatin-based chemotherapy. However, promising results have been achieved in
      chemo-naive patients in combination with taxanes or gemcitabine, though at the
      price of relevant toxicity. A modest activity has been shown by ifosfamide in
      renal cancer (including the sarcomatoid variant) and in hormone-refractory
      prostate cancer, which unfortunately respond poorly to cytotoxic chemotherapy. No
      results of ifosfamide in penile carcinoma are available so far.

PMID- 14586153
TI  - Ifosfamide in germ cell tumors.
AB  - Ifosfamide has always had significant single-agent activity in patients with germ
      cell tumors. We first began studies of cisplatin + ifosfamide combination
      chemotherapy as salvage chemotherapy in 1982. The regimen of etoposide (VP-16) +
      ifosfamide + cisplatin (VIP) was initially utilized as third-line chemotherapy.
      Even in this refractory setting, we were able to cure a small cohort of patients.
      Ifosfamide-cisplatin combination chemotherapy then became a standard second-line
      chemotherapy program, and achieved a 25% cure rate. Subsequent phase III studies
      compared VIP to bleomycin + etoposide + cisplatin (BEP) as initial chemotherapy.
      Although the results of the ifosfamide-based regimen were slightly better, there
      was no statistically significant difference and BEP was less toxic. However, for
      individual patients with concern for bleomycin-induced pulmonary fibrosis, VIP
      remains an attractive first-line regimen.

PMID- 14586154
TI  - Ifosfamide with regional hyperthermia in soft-tissue sarcomas.
AB  - For high-risk soft tissue sarcomas (HR-STS) of adults, new treatment strategies
      are needed to improve outcome with regard to local control and overall survival.
      Therefore, systemic chemotherapy has been integrated either after (adjuvant) or
      before (neoadjuvant) optimal local treatment by surgery and radiotherapy in HR
      STS. The combination with regional hyperthermia as a new treatment strategy seems
      to open a new therapeutic window.

PMID- 14586155
TI  - Ifosfamide in the adjuvant therapy of soft tissue sarcomas.
AB  - Ifosfamide and anthracyclines are the only active agents in advanced soft tissue
      sarcomas. Doxorubicin was always used in sarcomas, whereas ifosfamide was
      reintroduced in the clinic after the discovery of mesna which prevents its
      typical dose-limiting toxicity: hemorrhagic cystitis. In the adjuvant setting,
      doxorubicin was used alone or in combination in the first-generation trials,
      whereas its parent compounds epirubicin and ifosfamide were employed in the
      second-generation adjuvant trials, which started in the early 90s. Other relevant
      aspects of the second-generation trials are the use of the hematopoietic growth
      factors and the increase of the dose intensity, the introduction of more
      restrictive selection criteria and the use of the two most active agents,
      ifosfamide and anthracyclines. Only the Italian cooperative trial has been
      concluded, and the results reported and updated. After a median follow-up of 89.6
      months (range 56-119), the intention-to-treat analysis still reveals a difference
      in overall survival which, however, is not statistically significant. However,
      the 5-year overall survival estimate, which is a reasonable end point for the
      survival analysis of adjuvant treatment in soft tissue sarcomas, was 66.0 and
      46.1% for the treatment and the control groups, respectively (p = 0.04).

PMID- 14586156
TI  - Ifosfamide in hematological malignancies of adults.
AB  - Ifosfamide is an alkylating agent with a broad spectrum of activity in solid
      tumors and hematological malignancies. In this review we will illustrate its use
      in the treatment of lymphomas and Hodgkin's disease and the results of the
      principal studies which have investigated ifosfamide-containing regimens.
      Ifosfamide has been mainly used, in combination with other drugs, as a component
      of salvage regimens for relapsed or primarily refractory lymphoma. These regimens
      induced a variable clinical response rate (complete remissions ranging from 6 up
      to 73% and overall response rate from 24 to 72%). High-dose ifosfamide, in
      combination with etoposide or mitoxantrone, showed a good potential for
      mobilization of peripheral stem cells while reducing the tumor burden. Ifosfamide
      based regimens are also being evaluated in the treatment of newly diagnosed
      patients in sequential, response-based protocols, using many non-cross-resistant
      drugs.

PMID- 14586157
TI  - Blood stem cell collections after mobilization with combination chemotherapy
      containing ifosfamide followed by G-CSF in multiple myeloma.
AB  - High-dose chemotherapy with autologous peripheral blood stem cell transplantation
      is the standard treatment of patients with multiple myeloma today. In this study
      we used a combination mobilizing chemotherapy containing ifosfamide with G-CSF
      before stem cell collection. The chemotherapy regimen consisted of ifosfamide
      (2,500 mg/m(2) days 1-3), epirubicin (100 mg/m(2) day 1) and etoposide (150
      mg/m(2) days 1-3) followed by G-CSF (5 mug/kg from day 5). In 30 younger patients
      (median age 51 years; range 41-60 years) who received the IEV regimen in 100%
      dosage, a median of 11.15 x 10(6) CD34(+) cells/kg (range 0-44.60 x 10(6) CD34(+)
      cells/kg) was collected. In 22 elder patients (median age 64 years; range 59-72
      years) similar collection results were obtained with a median of 10.82 x 10(6)
      CD34(+) cells/kg (range 0.99-42.22 x 10(6) CD34(+) cells/kg) after the IEV
      regimen in 75% dosage. The pretreatment chemotherapy cycles before mobilization
      were fewer in elder patients with a median of 0 cycles (range 0-7 cycles)
      compared with younger patients with a median of 4 cycles (range 0-7 cycles).
      These collection results were favorable and allowed to support a tandem
      transplantation procedure in younger and elder patients in 97 and 95%,
      respectively. In the majority of patients, the hematological toxicity of IEV was
      of WHO grade 3/4. The extramedullary toxicity was mild to moderate and there were
      only few cases (5-10%) of relevant nephrotoxicity or neurotoxicity associated
      with the application of ifosfamide.

PMID- 14586158
TI  - Ifosfamide in pediatric solid tumors.
AB  - Phase II studies conducted in Europe and the USA on pediatric solid tumors have
      shown that ifosfamide, as a single agent, is an active drug against a variety of
      neoplasms - rhabdomyosarcoma (RMS), some non-RMS soft tissue sarcomas, Wilms'
      tumor, bone sarcomas and neuroblastoma. Furthermore, an increase in tumor
      response rate has been observed when ifosfamide has been used in combination with
      other drugs. The usual dose of ifosfamide varies from 1.8 to 3 g/m(2)/day for 2-5
      days according to the different regimens. Some controversies still exist on the
      modality of drug administration and more precisely on the time of infusion,
      however in pediatric practice, short infusion (e.g. 3 h) is usually preferred
      because of the reduced neurotoxicity in comparison to lengthier administration
      (e.g. 24 h). Ifosfamide is currently included in the standard therapy of
      pediatric bone and soft tissue sarcomas. It is also used in a selected high-risk
      group of patients with Wilms' tumor, neuroblastoma and germ cell tumors.

PMID- 14586159
TI  - Three-month treatment course of methylphenidate increases plasma levels of
      dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulfate (DHEA-S) in
      attention deficit hyperactivity disorder.
AB  - Methylphenidate is considered by many to be the treatment of choice for attention
      deficit hyperactivity disorder (ADHD). Methylphenidate exerts its therapeutic
      effects through the dopaminergic, serotonergic and noradrenergic systems, however
      its effects on other neurophysiological systems, such as the neurosteroidal
      system, remain unknown. Dehydroepiandrosterone (DHEA) and its sulfate ester (DHEA
      S) are neuroactive steroids with effects on several neurophysiological and
      behavioral processes. The purpose of the present study was to determine the
      effect of 3 months of treatment with methylphenidate on circulatory DHEA, DHEA-S,
      and cortisol in children with ADHD. The study population consisted of 15 boys
      (aged 11.5 +/- 1.6 years) with ADHD, combined type. Subjects were evaluated
      before and after methylphenidate treatment with a specific rating scale for the
      assessment of inattention and impulsivity in ADHD. Results show that treatment
      led to significant clinical improvement in all subjects. Furthermore, following 3
      months of treatment, there was a significant increase in serum levels of DHEA and
      DHEA-S but not in circulatory levels of cortisol. The mean rate of increase in
      DHEA levels was 23 and 53.6% in DHEA-S. Our findings suggest that DHEA and DHEA-S
      may play a role in the therapeutic effects of methylphenidate. Several mechanisms
      to explain this action are proposed, including involvement of the serotonergic,
      GABA-ergic and noradrenergic pathways.

PMID- 14586160
TI  - Chronic, but not acute, clomipramine or fluoxetine treatment reduces the
      spontaneous firing rate in the mesoaccumbens neurons of the rat.
AB  - In the present study, single-unit extracellular recording was used in male Wistar
      rats to compare the effects of a single dose (acute treatment) and a 21-day
      regimen (long-term treatment) with clomipramine (2.5 mg/kg) and fluoxetine (1.0
      mg/kg) on the spontaneous firing rate of nucleus accumbens (NAcc) neurons
      connected with the ventral tegmental area (VTA). A single injection of
      clomipramine or fluoxetine did not modify the firing rate of NAcc neurons as
      compared with the control group, whereas a 21-day regimen reduced the firing rate
      in comparison with a 21-day saline-treated group, specifically for NAcc neurons
      that were inhibited by VTA electrical stimulation. These results demonstrate that
      chronic, but not acute, clomipramine or fluoxetine treatment reduces the firing
      rate of mesoaccumbens neurons, probably by dopaminergic activation, supporting
      the hypothesis that the NAcc is involved in the actions of at least these
      antidepressants. However, additional experiments need to be performed in order to
      delineate the mechanisms by which chronic clomipramine and fluoxetine treatment
      reduces the firing rate of NAcc neurons in the rat.

PMID- 14586161
TI  - Altered cardiovascular responses to nitrosorbide in alcohol withdrawal.
AB  - The cardiovascular effects and pharmacokinetics of a single dose (20 mg
      sublingually) of isosorbide dinitrate (ISDN) were studied in 9 alcohol-dependent
      men during alcohol withdrawal syndrome (AW) on day 1 and after the resolution of
      AW on day 10. At the onset of AW, ISDN and its metabolites caused a hypotensive
      effect, which was increased on day 10, while no differences in ISDN-induced
      decrease in stroke volume were observed. Tachycardiac response to ISDN was more
      pronounced at onset of AW. On day 10, the AUC(0-1.5 h), C(max) and t((1/2)) of
      ISDN were increased compared with day 1. The results of this study suggest that
      nitric oxide may modulate the cardiovascular system in AW.

PMID- 14586162
TI  - Sleep disturbance in unipolar and bipolar depression: relationship to psychiatric
      family history.
AB  - Eighty depressed patients (40 bipolar and 40 unipolar) were personally
      interviewed in order to assess the relationship of disturbed sleep with
      psychiatric family history. Complaints of unsatisfactory sleep quantity and/or
      quality were more common among patients with a negative than among those with a
      positive family history for either any major psychiatric disorder (74.5 vs.
      43.3%, p < 0.01) or only a mood disorder (68.4 vs. 43.5%, p < 0.05); this was
      more pronounced in bipolar patients. Results were confirmed when demographic
      variables and clinical characteristics of the disease were taken into
      consideration through the use of multiple logistic regression analysis. It is,
      thus, suggested that the mechanisms underlying disturbed sleep during a major
      depressive episode are different to those associated with the familial
      predisposition for depression.

PMID- 14586163
TI  - Temporomesial activation in young females associated with unpleasant words
      concerning body image.
AB  - Previous behavioral studies suggest that people who have an abnormal eating
      behavior may perceive information concerning body image distortion more
      aversively than others. We performed a functional magnetic resonance imaging
      (fMRI) study on 15 young women, using an emotional decision task including
      unpleasant words concerning body image and neutral words. The left amygdala and
      right parahippocampal gyrus were activated by unpleasant words concerning body
      image relative to neutral words. In addition, activation of the right
      parahippocampal gyrus was negatively correlated with the severity of
      psychological and behavioral problems assessed by the Eating Disorder Inventory
      2. This activation also positively correlated with the subjects' rating of
      pleasantness of words concerning body image. These results demonstrated that the
      temporomesial area plays an important role in the perception of unpleasant words
      concerning body image. In particular, it is suggested that the right
      parahippocampal gyrus may be associated with subjective sensitivity to unpleasant
      information concerning body image.

PMID- 14586164
TI  - Pretreatment interhemispheric EEG coherence is related to seizure duration in
      right unilateral electroconvulsive therapy.
AB  - OBJECTIVE: The relationships between pretreatment EEG parameters and seizure
      duration in electroconvulsive therapy (ECT) were studied in order to provide
      information useful for the prediction of ECT-induced seizures. METHODS: In 16
      depressed patients treated with right unilateral ECT, pretreatment absolute band
      powers and interhemispheric coherences were assessed and correlated with the
      duration of the first ECT-induced seizure. RESULTS: Interhemispheric coherence
      for the central electrodes in the fast alpha band was positively correlated with
      seizure duration. CONCLUSIONS: Interhemispheric coherence may reflect, in a
      quantitative manner, cortico-cortical transmission via commissural pathways
      required for the generation of a generalized seizure through right unilateral
      stimulation. It may represent a useful parameter with respect to seizure
      threshold with potential therapeutic implications for ECT.

PMID- 14586165
TI  - Pain thresholds as a putative functional test for cerebral laterality in major
      depressive disorder and panic disorder.
AB  - OBJECTIVE: Both major depressive disorder (MDD) and panic disorder (PD) exhibit
      an illness-related functional cerebral laterality with a frontal right/left
      asymmetry. Using experimental pain lateralization as a putative indicator of
      functional cerebral laterality, we assessed body side differences in pressure,
      cold and heat pain thresholds in patients with MDD and PD as well as in healthy
      control subjects (HC). To control for an attentional bias in perception, reaction
      times for selective attention were also measured for both visual fields. METHOD:
      21 inpatients with MDD, 21 inpatients with PD (DSM-IV diagnosis) and 20 HC
      subjects, all right-handed, were investigated drug free. Pain thresholds for
      pressure, cold and heat were assessed at the right and left forearm or hand. A
      neuropsychological standard test was used to measure selective attention (signal
      detection, Wiener Testsystem), which allows for the discrimination between left
      and right visual field stimulus processing. RESULTS: In all participants, a left
      sided increased pain sensitivity could be verified by using pressure pain, but
      not by thermal pain (cold, heat). The diagnosis of MDD or PD had no influence on
      pain threshold lateralization. There were no differences in reaction times of
      selective attention between the groups of patients and the HC. Neither did
      stimulus presentation in the left or right visual field affect reaction time
      differently. CONCLUSION: Body side asymmetry of pain perception was only found
      for pressure pain targeting mainly deep tissue (muscle) nociception. This
      asymmetry, however, cannot be regarded as an indicator of a pathological
      functional cerebral laterality in MDD and PD.

PMID- 14586166
TI  - EEG alterations in subjects at high familial risk for Alzheimer's disease.
AB  - Twenty first-order relatives of patients with early-onset Alzheimer's disease
      (AD; mean age 43.7 +/- 1.3 years), 20 patients with early-onset AD (mean age 65.7
      +/- 0.9 years) and age-matched normal controls for the relatives and the patients
      underwent quantitative EEG (qEEG) examinations. In AD patients, delta and theta
      relative power values were increased and alpha relative power was decreased
      compared with normal controls. The AD patients' relatives had normal resting EEG
      parameters. Under hyperventilation in the AD relatives, synchronous high-voltage
      delta and theta activity and sharp waves were revealed, theta and delta relative
      powers were increased and alpha relative power was decreased compared with the
      resting EEG in the same persons. Moreover, under hyperventilation, the theta and
      delta relative powers in the EEG of the relatives were higher, and the alpha
      relative power was lower compared with the EEG of normal controls under the same
      conditions. It is suggested that the excitotoxic processes and oxidative stress
      underlie the EEG alterations in the AD patients' relatives and that these
      alterations may be related to the further AD development.

PMID- 14586167
TI  - Characterization of the CNS effects of naftidrofuryl (Praxilene) by quantitative
      EEG and functional MRI: a study in healthy elderly subjects.
AB  - In the present study, we investigated the effects of a single and a repeated (5
      days) administration of naftidrofuryl, a serotonin 5-HT2 receptor inhibitor
      having neuroprotective properties, on functional brain physiology in male healthy
      elderly subjects, using quantitative electroencephalography (EEG) and functional
      magnetic resonance imaging (fMRI). Twelve subjects aged 60 +/- 3.8 years
      completed the quantitative EEG study, where the effects of 400 and 600 mg were
      assessed, and 12 other subjects (aged 56 +/- 4.7 years) completed the fMRI study,
      where the effect of 400 mg was assessed on the brain activation induced by the
      continuous performance test (CPT). Naftidrofuryl induced a transient reduction in
      alpha activity followed by a specific synchronisation of the 9.5- to 11-Hz EEG
      activity most pronounced after repeated administration. Such regimen also
      increased the CPT-induced brain activation visualized by way of fMRI. The results
      of the present study can be interpreted at the functional level that
      naftidrofuryl induced an improved level of vigilance or an increased capacity of
      alertness in healthy elderly subjects.

PMID- 14586168
TI  - Human organic anion transporter 3 (hOAT3) can operate as an exchanger and mediate
      secretory urate flux.
AB  - BACKGROUND/AIMS: Renal secretion of organic anions is critically dependent on
      their basolateral uptake against the electrochemical gradient. Due to their
      localization, two transporters are likely involved, namely OAT1 and OAT3. While
      OAT1 as an exchanger clearly operates in the secretory direction, OAT3 in its
      previously supposed mode as a uniporter should move anionic substrates from cell
      to blood. It would thus dissipate gradients established by OAT1 of common
      OAT1/OAT3 substrates. In the present study we therefore reinvestigated the
      driving forces of human OAT3. METHODS: The human OAT3 obtained Xenopus laevis
      oocyte expression system, hOAT3-mediated transport of estrone sulfate (ES) and
      dicarboxylates was assayed for cis-inhibition and/or trans-stimulation in both
      the uptake and efflux direction. RESULTS: hOAT3-mediated efflux of glutarate
      (GA), can be significantly trans-stimulated by a variety of ions with high cis
      inhibitory potency, including GA (282%), alpha-ketoglutarate (476%), p
      aminohippurate (179%), and, most notably, urate (167%). Urate cis-inhibited ES
      uptake with an IC(50) close to normal serum urate concentrations. CONCLUSION:
      These data indicate that OAT3 does not represent a uniporter but operates as an
      organic ion%dicarboxylate exchanger similar to OAT1, and may mediate renal urate
      secretion.

PMID- 14586169
TI  - Intracellular pH activates membrane-bound Na(+)/H(+) exchanger and vacuolar H(+)
      ATPase in human embryonic kidney (HEK) cells.
AB  - Mammalian cells regulate their cytosolic pH through a variety of proton extruding
      and bicarbonate loading mechanisms. The human embryonic kidney cell line HEK 293
      is thought to show some characteristics of proximal tubule cells. The present
      study was performed to investigate the activity of proton extruding mechanisms
      (i.e. Na(+)/H(+) exchange and/or V-H(+)-ATPases) and the influence of
      intracellular pH (pH(i)) on the activation of these transport processes. At
      resting pH(i) (7.4) and in the absence of bicarbonate, removal of extracellular
      Na(+) did not alter pH(i) Intracellular acidification (pH(i) approximately 6.2)
      after a NH(4)Cl prepulse (20 mM) followed by exposure to a Na(+) free bath
      solution led to a slow pH(i) recovery (with a delay of 5 min), which was
      inhibited by the specific vacuolar H(+)-ATPase inhibitor bafilomyocin. There was
      no Na(+)-dependent pH(i) recovery upon exposure to Na(+) after a short
      intracellular acidification (less than 5 min). However, when the intracellular
      acidification phase was extended, the activation of a Na(+)-dependent pH(i)
      recovery was seen. This Na(+)-dependent pH(i) recovery was inhibited by 30 microM
      EIPA but not by 2 microM EIPA or less, suggesting the involvement of NHE3.
      Western blot analysis confirmed the presence of NHE3 protein in HEK 293 cells.
      Disruption of the microtubular network by colchicine (20 microM) did not
      significantly inhibit the rate of Na(+)-independent or dependent pH(i) recovery
      indicating that activation of both H(+)-ATPase, and the NHE were not due to
      stimulated trafficking of the transport proteins or some activators to the
      membrane. We conclude that a) the plasma membrane of HEK293 cells contains both,
      NHE and H(+)-ATPase and b) both H(+) extrusion systems are inactive at neutral
      pH(i), c) a decrease of cytosolic pH to 6.5 activates both transport proteins in
      a slow, time-dependent manner.

PMID- 14586170
TI  - Expression of the electrophysiological system during murine embryonic stem cell
      cardiac differentiation.
AB  - BACKGROUND: Stem cell based replacement therapy is envisioned as a method to
      repair failing hearts suffering from cardiomyocyte loss. To prevent potentially
      lethal arrhythmias, the donor cellular electrophysiological make-up should match
      with the acceptor tissue. To engineer the desired electrophysiological phenotype,
      the underlying molecular regulation of ion channels and gap-junction proteins
      should be clarified first. METHODS: We established the expression of seven main
      cardiac ion channel a-subunits and four b-subunits using semiquantitive RT-PCR
      and two major cardiac gap-junction proteins by immunohistochemistry during the
      differentiation process of murine ES cells into cardiomyocytes. RESULTS: Ion
      channel mRNA expression profiles display sequential upregulation. Connexin-40 and
      -43 expression is low in early cardiomyocytes, increased expression rates were
      found in subsequent differentiation phases. CONCLUSION: Cardiac differentiation
      of mouse embryonic stem cells is characterized by a sequential upregulation of
      the main cardiac ion channels and connexins.

PMID- 14586171
TI  - Estimation of action potential changes from field potential recordings in
      multicellular mouse cardiac myocyte cultures.
AB  - BACKGROUND: Extracellular recordings of electrical activity with substrate
      integrated microelectrode arrays (MEAs) enable non-invasive long-term monitoring
      of contracting multicellular cardiac preparations. However, to characterize not
      only the spread of excitation and the conduction velocity from field potential
      (FP) recordings, a more rigorous analysis of FPs is necessary. Therefore in this
      study we aim to characterize intrinsic action potential (AP) parameters by
      simultaneous recording of APs and FPs. METHODS: A MEA consisting of 60 substrate
      integrated electrodes is used to record the FP-waveform from multicellular
      preparations of isolated embryonic mouse cardiomyocytes. Simultaneous current
      clamp recordings in the vicinity of individual microelectrodes and
      pharmacological interventions allowed us to correlate FP and AP components and
      their time course. RESULTS: The experiments revealed a linear relationship
      between AP rise time and FP rise time as well as a linear relationship between AP
      duration and FP duration. Furthermore a direct contribution of the voltage
      dependent Na(+)- and Ca(2+)-current to the FP could be identified. CONCLUSION:
      The characterization of the FP allows us for the first time to estimate AP
      changes and the contribution of individual current components to the AP by the
      help of non-invasive recording within a multicellular cardiac preparation during
      long-term culture.

PMID- 14586172
TI  - Cdk7 functions as a cdk5 activating kinase in brain.
AB  - Activity of Cdk5, which is essential for CNS development, depends on its
      association with p35 (or truncated p25) or p39, but the regulatory mechanisms
      whereby Cdk5 is activated have not yet been fully elucidated. Studies on PC12
      cells showed that Cdk5/p25 activity is modulated by an unidentified kinase that
      phosphorylates Cdk5 at Ser159 and enhances its kinase activity (Sharma et al.,
      1999 PNAS USA 96,11156). In this study, we have partially purified a bovine brain
      enzyme that can phosphorylate the Cdk5(149-163) peptide but not the Cdk5(149
      163)A159 peptide. The enzyme, which contains Cdk7, cyclin H, and Mat1,
      specifically phosphorylates Ser159 of Cdk5(149-163) and enhances Cdk5/p25
      activity. The active Cdk7-containing enzyme also phosphorylates and activates wt
      Cdk5 but not mutated Cdk5(Ser159Ala). Likewise, Cdk7 or cyclin H
      immunoprecipitate from mouse brain specifically phosphorylates wt Cdk5 at Ser159
      and enhances Cdk5/p25 activity. Conversely, blocked Cdk7 immunoprecipitate does
      not phosphorylate nor activate Cdk5. In addition, the Cdk7 substrate, CTD of
      RNAPII, causes a dose-dependent decline in Cdk5 activation by Cdk7. These
      findings indicate that Cdk7 functions as a Cdk5 activating kinase in brain.
      Indeed, elevated Cdk5 activity in the developing E18 mouse brain coincides with
      increased Cdk7 kinase activity.

PMID- 14586173
TI  - Heat shock - induced Hsp70 expression in murine astrocytes does not require
      poly(ADP-ribose) polymerase activity.
AB  - Poly(ADP-ribose) polymerase (PARP) activity is involved in DNA repair,
      replication, recombination, and transcription. Extensive activation of the most
      abundant PARP, PARP-1, during ischemia or inflammation can promote cell death.
      PARP inhibitors reduce this cell death and are currently under investigation for
      use as therapeutic agents. A recent study found that PARP activation was required
      for Hsp70 upregulation in heat-exposed Drosophila larvae. Here we sought to
      determine whether PARP activity is likewise required for Hsp70 upregulation in
      mammalian cells, since many of the settings in which PARP inhibitors are
      candidate therapeutic agents are also settings in which Hsp70 expression is an
      important component of the stress response. We examined this issue using murine
      astrocyte cultures, a mammalian preparation in which the Hsp70 response has been
      well characterized, and found that PARP inhibitors had no effect on heat shock
      induced Hsp70 protein expression. PARP-1(-/-) astrocytes gave similar results.
      The present findings indicate that PARP activity, and specifically PARP-1, is not
      required for upregulation of Hsp70 expression in mammalian cells.Basel

PMID- 14586174
TI  - Pepsinogen C expression in intestinal IEC-6 cells.
AB  - Pepsinogen C (PGC) is the inactive precursor of pepsin C, which is a member of
      the aspartic proteinase family of proteolytic enzymes, and is found within the
      vertebrate stomach. The precursor molecule is synthesised within the gastric
      epithelial cells and secreted into the gastric lumen where it undergoes an
      autocatalytic activation under acidic conditions to the proteolytic molecule.
      However, the synthesis of PGC has also been reported in numerous non-gastric
      tissues including the prostate gland and the Brunner's gland of the small
      intestine. The physiological significance of PGC in these tissues is not known
      and studies are limited by the lack of appropriate in vitro cell models. We
      report here the use of the rat intestinal cell line, IEC-6, as an in vitro model
      to study the role of pepsinogen C in the intestine. PGC expression was detected
      in the IEC-6 cells by RT-PCR and immunocytochemistry, using a PGC specific
      antibody, localised the protein to cytoplasmic secretory granules. Enzymatic
      assay confirmed the presence of a functional protein exhibiting pepsin activity.
      Using semi-quantitative RT-PCR we showed that PGC gene expression was up
      regulated by the gastro-intestinal hormones gastrin and secretin, and forskolin
      which stimulates adenylate cyclase activity. This study demonstrates that the IEC
      6 cells provide a unique in vitro model for studying pepsinogen C and its
      potential role(s) in the small intestine.

PMID- 14586175
TI  - Phagocytosis and allogeneic T cell stimulation by cultured human osteoblast-like
      cells.
AB  - BACKGROUND/AIMS: The antigen phenotype of human osteoblast-like cells suggests
      that they are related to other cellular populations and may also have immunologic
      functions in common. METHODS: Flow cytometry and transmission electron microscopy
      were used to show the phagocytotic activity of osteoblast-like cells in culture.
      The allogeneic stimulation of T cells by human osteoblast-like cells was
      determined by the measurement of T cell proliferation. RESULTS: We demonstrated
      in vitro that human osteoblast-like cells isolated from normal bone specimens
      obtained during mandibular osteotomy can phagocytose particles of different
      nature and size and can stimulate allogeneic T cells. Phagocytosis of
      microorganisms (E.coli, Klebsiella or C. albicans) was observed, although at a
      very low rate of activity in comparison with the phagocytosis of latex particles.
      CONCLUSION: Our results suggest that human osteoblast-like cells may perform
      immunologic functions and act as antigen presentation cells.

PMID- 14586176
TI  - The effect of crude and purified Cerastes vipera venom protein fractions on
      respiratory chain function in cultured human fibroblasts.
AB  - This study was conducted to investigate the effect of crude and venom protein
      fractions of Cerastes vipera on the major enzymatic components of the respiratory
      chain in cultured human fibroblasts. Cerastes vipera crude venom was fractionated
      into seven protein fractions by using 8% preparative native polyacrylamide gel
      electro-phoresis. The effect of crude venom and purified venom fractions (F1-F7)
      on respiratory chain function in cultured human fibroblasts was investigated.
      Confluent fibroblast cultures were incubated with crude venom and venom protein
      fractions for a fixed period of three hours at 37 degrees C. Crude venom and
      venom protein fractions 2, 4, 5 and 6 significantly increased the production of
      lactate as compared to control fibroblasts. The production of pyruvate was
      markedly decreased in all these cell lines. The ratio of lactate/pyruvate was
      increased in the cells and in the culture medium by crude venom and venom protein
      fractions 2, 4, 5 and 6. On the other hand fractions 1,3 and 7 exhibited no
      effect in relation to lactate and pyruvate production. Similarly the crude venom
      protein and venom protein fractions 2, 4, 5 and 6 significantly lowered the
      activity of the major enzymatic component of the respiratory chain in fibroblast
      mitochondria. In conclusion it is apparent that the crude and venom protein
      fractions 2, 4, 5 and 6 resulted in a significant lowering of the mitochondrial
      respiratory chain activity in cultured human fibroblasts.

PMID- 14586177
TI  - Proteasomal degradation of a trypanosomal ornithine decarboxylase.
AB  - Mammalian ornithine decarboxylase (ODC), which catalyses the first step in
      polyamine biosynthesis, has a very fast turnover. It is degraded by the 26S
      proteasome in an ubiquitin-independent process and the degradation is stimulated
      by polyamines in a feedback control of the enzyme. Interestingly, there is a
      major difference in the metabolic stability between ODCs from various
      trypanosomatids. Trypanosoma brucei and Leishmania donovani both contain stable
      ODCs, whereas Crithidia fasciculata has an ODC with a rapid turnover. In spite of
      the difference in stability there is a high degree of sequence homology between
      C. fasciculata ODC and L. donovani ODC. In the present study we demonstrate that
      C. fasciculata ODC is rapidly degraded also in mammalian systems like CHO cells
      and rabbit reticulocyte lysate, suggesting that the degradation signals of the
      enzyme are recognised by the mammalian systems. L. donovani ODC, on the other
      hand, is degraded very slowly in the same systems. The degradation of C.
      fasciculata ODC in the mammalian systems is markedly reduced by inhibition of the
      26S proteasome. However, unlike mammalian ODC, C. fasciculata ODC is not down
      regulated by polyamines. Thus, the turnover of C. fasciculata ODC and L. donovani
      ODC in the mammalian systems reflects the degradation of the enzyme in the
      parasites, making such systems potentially useful as complements to parasitic
      knockout models for further analysis of the mechanisms involved in the rapid
      degradation of C. fasciculata ODC.

PMID- 14586179
TI  - Relationship between resistance to erythropoietin and high anomalous hemoglobin
      levels in hemodialysis patients with beta-thalassemia minor.
AB  - In dialysis patients beta-thalassemia is a cause of resistance to erythropoietin
      (EPO). The aim of the present study is to evaluate the relationship between the
      amount of circulating anomalous hemoglobin chain and EPO resistance in
      hemodialysis. Ten hemodialyzed patients with beta-thalassemia minor were studied.
      The mean hemoglobin level was 9.22 +/- 0.91 g/dl, the HbA2 ranging between 5.6
      and 6.8%; the weekly EPO dose was 13,500 +/- 7,185 IU/week and significantly
      correlated with HbA2 (r = 0.965; p = 0.0001). When stratifying patients in two
      groups according to HbA2 level (LOW <6%, n = 4; HIGH >6%, n = 6; HbA2 levels,
      respectively, 5.7 +/- 0.1 and 6.4 +/- 0.3 g/dl, p = 0.002), it was evidenced that
      the need of EPO was 13,200 +/- 3,033 IU/week in LOW and 36,167 +/- 13,060 IU/week
      in HIGH (p < 0.001). The EPO Resistance Index in the two groups was 13.4 +/- 4.1
      IU/kg BW/week/g Hb in LOW and 21.9 +/- 10.0 in HIGH (p < 0.05). No differences
      were evidenced between the two groups regarding age, dialysis, body weight, serum
      levels of urea nitrogen, creatinine, albumin, C-reactive protein, aluminum,
      ferritin, transferrin and parathyroid hormone. In conclusion, in patients with
      beta-thalassemia minor on chronic hemodialysis, the amount of anomalous
      hemoglobin chain directly correlate with EPO dose, strongly indicating the
      magnitude of resistance to erythropoietin.

PMID- 14586178
TI  - Effects of parathyroidectomy on iron homeostasis and erythropoiesis in
      hemodialysis patients with severe hyperparathyroidism.
AB  - AIMS: Secondary hyperparathyroidism (HPT) worsens anemia and may cause
      hyporesponsiveness to recombinant human erythropoietin therapy (r-HuEPO). To
      investigate the effect of parathyroidectomy (PTX) on iron homeostasis and
      erythropoiesis, we conducted a prospective study in chronic hemodialysis patients
      who underwent PTX. METHODS: Thirty-two patients were enrolled in this study.
      Based on the increases in hemoglobin level after PTX, patients were divided into
      responders and nonresponders. Iron homeostasis and erythropoiesis were assessed
      before and 1 and 3 months after PTX, hemoglobin and parathyroid hormone levels
      were monitored until 6 months after PTX. RESULTS: In the responders, increased
      hemoglobin levels were observed in 15 patients at 1 and 3 months after PTX (8.0
      +/- 0.8 g/dl vs. 9.2 +/- 1.3 and 10.1 +/- 0.9 g/dl, p < 0.05). The nonresponders
      had higher pre-PTX hemoglobin levels than the responders (10.3 +/- 1.6 g/dl vs.
      8.0 +/- 0.8 g/dl, p < 0.05). There was no further increase in hemoglobin at 6
      months compared to 3 months after PTX in both groups. In neither group did PTX
      affect serum ferritin, transferrin saturation and serum erythropoietin level.
      Serum soluble transferrin receptor (sTfR) concentration was found to be higher in
      responders than in nonresponders (3.32 +/- 1.28 mg/l vs. 1.70 +/- 0.31 mg/l, p <
      0.05). CONCLUSIONS: We conclude that PTX can improve anemia in hemodialysis
      patients with severe hyperparathyroidism and greater resistance to r-HuEPO
      therapy. The reversing of anemia does not involve altering iron mobilization. Pre
      PTX hemoglobin and serum sTfR levels can predict the effect of PTX on correcting
      anemia.

PMID- 14586180
TI  - Electrocardiographic changes during hemodiafiltration with different potassium
      removal rates.
AB  - BACKGROUND/AIMS: Sudden K removal is thought to be implicated in ECG alterations
      observed during hemodialysis (HD). The effects of the K removal rate on ECG
      derived parameters have been investigated. METHODS: Two different
      hemodiafiltration (HDF) schedules were used for 10 HD patients: the dialysate K
      concentration was kept constant in HDFst, while in HDFK it was decreased during
      the session in order to maintain a uniform plasma-dialysate K gradient. A 12-lead
      Holter monitor was used to acquire the ECG in the course of the treatments.
      Classical ECG parameters and overall indices for quantifying ventricular
      repolarization abnormalities were evaluated. RESULTS: Several ECG parameters were
      affected by both HD therapies (ST depression, QRS amplitude and QT dispersion),
      but only indices of the homogeneity of repolarization (PCA-T, E1-T) were
      significantly affected by the K removal rate. CONCLUSION: The present study
      confirms the large impact of HD therapy on ECG. The analysis of the spatial T
      wave complexity points out the intrinsic arrhythmogenic implications of the K
      removal rate.

PMID- 14586181
TI  - Effect of local physical training on the forearm arteries and veins in patients
      with end-stage renal disease.
AB  - AIM: We investigate the effects of local training on the forearm vessels in
      patients with end-stage renal disease. METHODS: Fourteen hemodialysis patients
      were included. Handgrip training was performed for 8 weeks. The following
      parameters were measured at the beginning of the study and 4 and 8 weeks later:
      forearm circumference, maximal handgrip strength, and artery and vein parameters,
      including endothelium-dependent and endothelium-independent vasodilatation (using
      ultrasound and duplex Doppler scanning). RESULTS: The maximal handgrip strength
      increased significantly. The radial artery diameters were significantly higher
      after 8 weeks of training. The endothelium-dependent vasodilatation was found to
      be significantly increased after 4 and 8 weeks of training. The maximal vein
      diameters increased significantly with training, with preserved distensibility.
      CONCLUSIONS: The present study suggests that regular handgrip training increases
      the diameters of forearm vessels. It also improves endothelium-dependent
      vasodilatation. These changes point to the possible beneficial effects of daily
      handgrip training in chronic renal failure patients before arteriovenous fistula
      construction.

PMID- 14586182
TI  - The prognostic role of atrial natriuretic peptides in hemodialysis patients.
AB  - BACKGROUND: It is well known that plasma atrial natriuretic peptide (ANP) is an
      indicator of extracellular fluid volume expansion and that plasma ANP is
      considered to be a marker for setting the proper dry weight of HD patients.
      Although the plasma ANP is a prognostic predictor of cardiac death, the
      prognostic role of ANP in HD patients has yet to be elucidated. In this study, we
      investigated the prognostic role of ANP in HD patients. METHODS: Plasma ANP
      concentrations were measured in 105 HD patients after HD. Multiple regression
      analysis was performed to determine the major factors causing increased plasma
      ANP concentrations. Cardiac mortality was monitored for 24 months after baseline
      analysis, and the prognostic role of ANP was examined by Cox proportional hazards
      regression analysis. RESULTS: Multiple regression analysis showed that
      cardiovascular disease (CD) and age were independent factors for elevated ANP (R2
      = 0.298, p < 0.0001). During a 24-month follow-up period, cardiac death occurred
      in 11 patients. Kaplan- Meier survival estimates of patients from varying plasma
      ANP levels (<50 and >50 pg/ml) differed between the two groups (p < 0.0001). The
      group with the higher ANP level (>50 pg/ml) had the lower survival. When compared
      with patients with ANP <50, the hazard ratios for cardiac death of patients with
      ANP of >50 pg/ml were 32.0 (95% confidence interval (CI) 4.1 to 252.4).
      Univariate Cox proportional hazards model showed that ANP, left ventricular
      ejection fraction (LVEF), LVMI, age, serum albumin and C-reactive protein (CRP)
      were significantly associated with the risk of cardiac mortality. By stepwise
      multivariate Cox proportional hazards analysis, only ANP, LVMI and CRP remained
      powerful independent predictors of cardiac death. The relative risk ratios were
      3.483 (95% CI 1.640-7.397) for ln ANP, 1.023 (1.008-1.038) for LVMI, and 1.379
      (1.115-1.705) for CRP. CONCLUSION: High plasma ANP level of post-HD were strongly
      associated with CD and age. Post-HD ANP level may be a reliable parameter for
      assessing the risk for cardiac death in HD patients by providing prognostic
      information independent of other variables previously reported.

PMID- 14586183
TI  - Relationship between natriuretic peptides and residual diuresis during continuous
      hemodiafiltration.
AB  - BACKGROUND: The reasons for the decrease or increase of urine output following
      the start of continuous venovenous hemodiafiltration (CVVHDF) have not yet been
      explained sufficiently. The renoprotective properties of natriuretic peptides
      were described. METHODS: The levels of atrial natriuretic peptide (ANP) and brain
      natriuretic peptide (BNP) were measured in 23 mechanically ventilated patients
      before and during the first 48 h of CVVHDF. Samples were drawn both from the
      ports proximal and distal to the filter. The results were compared between the
      group where daily diuresis (Vu) remained low or decreased and the group where
      diuresis increased to the level of 1.5 ml x kg(-1) x h(-1) or higher after 48 h
      of treatment. Left ventricular dysfunction (LVD) was defined as LV ejection
      fraction below 40%. A control group consisted of 10 patients exposed to abdominal
      surgery. RESULTS: The average AVdiff (%) of ANP and BNP on filter were
      insignificant. Patients with increasing diuresis (n = 12) had significantly lower
      levels of both ANP (p < 0.001) and BNP (p < 0.005) than the patients with
      decreasing diuresis (n = 11). Significant correlations were revealed for ANP and
      Vu (p < 0.01) and for BNP and Vu (p < 0.05). The levels of both peptides were
      grossly elevated in comparison to controls and were predictive of survival. The
      differences between cardiac and non-cardiac patients were significant both for
      ANP and for BNP. CONCLUSIONS: The elimination of ANP and BNP by the CVVHDF is
      negligible. The levels of natriuretic peptides are inversely related to Vu and
      predict survival. ANP and BNP levels correlate with left ventricular function
      even during acute renal failure and CVVHDF.

PMID- 14586184
TI  - Coupled plasma filtration adsorption: rationale, technical development and early
      clinical experience.
AB  - The adjuvant treatment of sepsis remains a major therapeutic challenge. Blood
      purification is theoretically appealing if the humoral theory of sepsis is
      accepted as the basis for intervention. In this setting, blood purification would
      provide a broad-based restoration of humoral homeostasis thereby avoiding both
      excessive inflammation and counterinflammation. Several techniques of blood
      purification have been tried or are under active investigation. One of these is
      the so-called coupled plasma filtration adsorption (CPFA). CPFA is a novel
      extracorporeal blood purification therapy aimed at nonselectively reducing the
      circulating levels and activities of both pro- and anti-inflammatory mediators
      during sepsis and multiorgan failure. In vitro studies have shown CPFA to be
      effective in binding a broad range of such mediators proving its technical
      efficacy. Subsequent animal models have shown a beneficial effect on survival in
      endotoxemia. These studies have provided the necessary technical developments and
      biologic rationale for initial human studies. Two phase I/IIa clinical studies
      have now been performed. Both studies have shown that CPFA improves blood
      pressure and restores immune function in patients with severe sepsis and
      multiorgan dysfunction. In this article, we will discuss some of the basic
      principles involved in sorbent technology, and how these may contribute to
      treatment efficacy, review animal experiments with CPFA and finally discuss the
      results of recent human studies and their implications.

PMID- 14586185
TI  - HIV/AIDS knowledge and attitudes of STD clinic attendees in St. Petersburg,
      Russia.
AB  - Over the last several years, Russia has experienced dramatic increases in rates
      of HIV and other sexually transmitted disease (STDs). This study examined
      HIV/AIDS knowledge, attitudes toward condoms, and sources of information about
      HIV in a sample of 200 male and 200 female Russian STD clinic patients. Study
      participants displayed substantial knowledge deficits concerning AIDS and HIV
      transmission. Superior knowledge was associated with younger age, greater
      education, positive attitudes toward condoms, having more sources of information
      about HIV/AIDS, and believing that the government is telling the truth about
      AIDS. More-positive attitudes toward condoms were associated with having a larger
      number of information sources, greater HIV/AIDS knowledge, and not being in a
      steady relationship. Many participants reported not trusting government and media
      sources of information concerning AIDS. Participants also reported concerns
      regarding the low quality and high cost of condoms in Russia. Results of the
      study suggest that interventions designed to increase knowledge and awareness of
      AIDS among Russians at high risk for HIV are urgently needed.

PMID- 14586186
TI  - A cognitive-behavioral intervention to reduce HIV risk behaviors in crack and
      injection drug users.
AB  - This paper presents the results of a study evaluating the efficacy of a theory
      based cognitive-behavioral intervention to reduce HIV risk among street-based
      crack and injection drug users not currently in drug treatment in Long Beach,
      California. A nine-session, 4-month enhanced intervention (including HIV
      counseling and testing) was compared to a two-session standard counseling and
      testing intervention developed by the National Institute on Drug Abuse (NIDA) in
      terms of their efficacy for reducing drug- and sex-related risk behaviors. The
      theory-based enhanced intervention rarely was found to be different from NIDA's
      standard counseling and testing intervention in reducing both drug- and sex
      related risks, as indicated by cessation and/or reduction of drug use (measured
      by urine test and self-report), entry into drug treatment, and increased
      frequency of condom use. One of the few significant effects was that the enhanced
      intervention significantly increased injecting drug users' use of their own
      injection equipment. On the other hand, for both interventions, most risk
      behaviors were significantly reduced. It is concluded that the theory-based
      cognitive-behavioral intervention has limited advantage over the standard
      intervention in terms of both magnitude and frequency of HIV risk reduction
      achieved by high-risk, active drug users.

PMID- 14586187
TI  - Social capital as a predictor of adolescents' sexual risk behavior: a state-level
      exploratory study.
AB  - This exploratory study assessed the state-level association between social
      capital, poverty, and income inequality and adolescents' sexual risk and
      protective behaviors. A cross-sectional design using state-level correlations was
      employed. Seven outcome measures from the national 1999 Youth Risk Behavior
      Surveillance Survey were used. For females and males, social capital was
      significantly associated with five of the seven outcome measures (all
      associations p < 01). For females, the amount of variance explained by these
      correlations ranged from 23% to 45%; the range for males was 20% to 52%. Poverty
      was not a significant predictor of any outcome variable. Income inequality was a
      significant predictor of birth control usage among females, but in multivariate
      regression analyses, only social capital retained significance. Findings provide
      preliminary evidence that social capital may have a profound influence of
      adolescents' sexual risk and protective behaviors. Social capital was inversely
      correlated with sexual risk behaviors and positively correlated with protective
      sexual behaviors. Further and more comprehensive research involving social
      capital and adolescents is warranted.

PMID- 14586188
TI  - Promoting HIV testing among never-tested Hispanic men: a doctor's recommendation
      may suffice.
AB  - This study examined factors associated with HIV testing intentions among a
      community sample of 255 never-tested Hispanic men. It compared (1) men who
      intended to test in the next 6 months with those who did not and (2) men who
      intended to test only on the day of the interview with those who intended to test
      in the next 6 months. Eighty-four percent of men had never been offered testing.
      Yet, 86% would accept testing if recommended by their doctor. The strongest
      multivariate predictor of testing intention was willingness to accept a physician
      endorsed test. Almost 49% of men who intended to test in the next 6 months would
      only do so if the test were offered on the interview day. These findings
      highlight the importance of encouraging physicians, particularly in high
      prevalence areas, to routinely recommend testing. They also suggest that for some
      men, there is a window of opportunity for testing that does not endure.

PMID- 14586189
TI  - When HIV-prevention messages and gender norms clash: the impact of domestic
      violence on women's HIV risk in slums of Chennai, India.
AB  - This paper examines how marital violence affects women's ability to protect
      themselves from HIV/AIDS. In-depth interviews (n = 48) and focus groups (n = 84,
      3-7 per group) were conducted among men and women in two randomly selected slums
      of Chennai, India. The study showed that community gender norms tacitly sanction
      domestic violence that interferes with adopting HIV-preventive behaviors. Given
      the choice between the immediate threat of violence and the relatively
      hypothetical specter of HIV, women often resign themselves to sexual demands and
      indiscretions that may increase their risk of HIV acquisition. In conclusion,
      AIDS-prevention interventions must incorporate gender-related social contexts in
      settings where husbands strictly enforce their locus of control. HIV-prevention
      messages targeting men may effectively reduce women's exposure to HIV/AIDS.

PMID- 14586190
TI  - Correlates of sexual risk for HIV infection in female members of heterosexual
      California Latino couples: an application of a Bernoulli process model.
AB  - Individual HIV risk estimates were generated from reported sexual behavior for
      1,146 California Latino Couples Study participants (573 couples). These Bernoulli
      process model-based estimates proved strongly associated with individual sexually
      transmitted disease history. Mean estimated background risk from sexual contacts
      other than with their primary partner was substantially lower for the females
      than the males (1.4 vs. 7.4 per 10,000). After including their chance of
      infection from each other, mean net estimated risk was higher for the females
      than the males (9.2 vs. 8.6 per 10,000). Individual background risk was predicted
      by individual demographic and psychosocial characteristics (females: coefficient
      of concordance C = 0.84 predicting any (nonzero) risk; adjusted R(2) = 36%
      predicting level of risk, given any risk; males: C = 0.78; R(2) = 24%).
      Characteristics of women with higher risk primary partners were also identifiable
      (C = 0.65; R(2) = 13%). There was no significant negative association between the
      male partner's background sexual risk and the aggregate infectivity of the woman
      from him (taking into account the total number of their condom-protected and
      unprotected acts of different types).

PMID- 14586191
TI  - Intimate partner violence and HIV risk among urban minority women in primary
      health care settings.
AB  - This study describes the associations between intimate partner violence (IPV) and
      HIV risk among urban, predominantly minority women. Interviews were conducted
      with 1,590 women, predominantly African American and Latina, attending hospital
      based health care clinics. Approximately 1 in 5 women reported experiencing IPV
      in their current primary heterosexual relationships; about 1 in 8 women reported
      experiencing IPV in the preceding 6 months. Compared to women who reported no IPV
      in their primary relationships, women reporting past or current IPV perpetrated
      by their primary partners were more likely to report having multiple sexual
      partners, a past or current sexually transmitted infection (STI), inconsistent
      use or nonuse of condoms, and a partner with known HIV risk factors. These
      findings indicate that urban minority women experiencing IPV are at elevated risk
      for HIV infection, results that carry important implications in the efforts to
      improve HIV and IPV risk assessment protocols and intervention/prevention
      strategies for women in primary health care settings.

PMID- 14586192
TI  - Hoppers and oldheads: qualitative evaluation of a volunteer AIDS outreach
      intervention.
AB  - Qualitative research can play an important role in explaining outcomes of
      behavioral interventions and constitutes a largely unrealized potential of
      ethnographic methods in AIDS research. The Self Help in Eliminating Life
      Threatening Diseases (SHIELD) intervention trained African American injection
      drug users to conduct outreach among their drug-using peers and sexual partners.
      Though the intervention was not targeting adolescents, some participants chose to
      conduct outreach with youth fortuitously found on the street. Still others spoke
      to groups of youth in their homes. This paper seeks to understand the dynamics of
      outreach encounters between older, drug-using outreach workers and adolescents.
      Contextual features that were important in determining the quality of outreach
      encounters with youth included the setting (on the street or in the home),
      characteristics of the outreach worker such as gender, content of the outreach
      message, and style of interpersonal communication.

PMID- 14586193
TI  - Women's drug injection practices in East Harlem: an event analysis in a high-risk
      community.
AB  - This study described the most recent injection events of injection-drug-using
      women, determined the prevalence of HIV, hepatitis B (HBV), and hepatitis C
      (HCV), and identified significant predictors of injection-related risk behaviors.
      After validation of drug use, 185 street-recruited women participated in
      structured interviews and were offered HIV, HBV, and HCV testing and counseling.
      Interview topics included (1) demographic characteristics, (2) characteristics of
      injection partners (IPs), and (3) relevant situation-specific factors. Prevalence
      was 28% for HIV infection, 80% for HBV, and 70% for HCV. Injection events were
      either solitary (n = 110) or social (n = 75). Most were safe, and 75% of syringes
      used were obtained from a syringe exchange. Inferential analyses identified two
      variables that independently predicted unsafe events: (1) respondent had injected
      previously with her IP, and (2) her IP was her spouse or primary heterosexual
      partner. Two trends were identified: Injection events in which women felt "very
      close" to their IP or reported lack of control over injection practices tended to
      be unsafe. Although most events were safe, safe practices were not adhered to
      with spouses or primary partners. Syringe exchanges should be supported and may
      be an ideal setting for interventions targeted to drug-injecting couples.

PMID- 14586194
TI  - Medication management skill in HIV: I. Evidence for adaptation of medication
      management strategies in people with cognitive impairment. II. Evidence for a
      pervasive lay model of medication efficacy.
AB  - People with HIV-related cognitive impairment may change the way they manage
      medication regimens, relying on a fixed medication schedule each day to avoid
      missed doses. Using a medication recall diary, we identified people who took
      medication on exactly the same schedule over 3 days and those with more variable
      medication schedules. Patients with low scores on executive and psychomotor tests
      were more likely to report fixed medication schedules; memory performance, by
      contrast, was not associated with reported medication regimen. Patients with low
      scores on executive and psychomotor tests were also less accurate in pouring
      medicines in the Medication Management Test. More than three fourths of these
      HIV+ patients assumed that medicines with higher milligram dosages were stronger
      than medicines with smaller milligram dosages, even across different classes of
      medicines. In a non-HIV sample, 28% endorsed the belief, suggesting it is a
      widespread way of thinking about medication strength. A performance test of
      medication management sheds light on the ways patients take medicines and how
      beliefs about medicines affect medication regimens.

PMID- 14586195
TI  - Suicidal ideation among psychiatric patients with HIV: psychiatric morbidity and
      quality of life.
AB  - This study explored suicidality among 190 (68% male) participants in an HIV
      mental health clinic. Twenty-six percent had suicidal thoughts within 30 days of
      admission, 49% had a plan, and 48% expressed intent stating there was moderate or
      high likelihood they would take action. The most prevalent diagnoses among those
      with suicidal ideation were major depression (64%), drug dependence (52%), and
      depressive personality disorder (50%). In regression analyses, individuals with
      major depression, dysthymia, substance abuse, thought disorder, posttraumatic
      stress disorder, and borderline and avoidant personality disorders were at
      increased risk for suicidality whereas those with narcissistic personality
      disorder were at decreased risk. In addition, six of seven quality-of-life
      variables were associated with suicidal ideation, with the strongest correlations
      found for leisure/social (r =.36) and family/friends (r =.33). At-risk
      individuals, especially those with "dual disorders," unstable interpersonal
      relations, and a restricted social environment, should be carefully screened for
      suicidality.

PMID- 14586196
TI  - The drugs or the disease? Causal attributions of symptoms held by HIV-positive
      adults on HAART.
AB  - Studies of HIV-related symptom and treatment side effect prevalence often fail to
      distinguish individual causal attributions between the two types of problems.
      However, an understanding of causal appraisals is critical to clarifying and
      intervening on coping in the context of HIV symptoms and treatment side effects.
      The objectives of this study are (1) to present causal attributions of symptoms
      reported by HIV+ adults taking combination therapy and (2) to describe the
      differential impact on health-related quality of life. In a cross-sectional
      interview study, a convenience sample of 109 HIV-positive adults taking highly
      active antiretroviral therapy (HAART) were interviewed using a combination of
      self- and interviewer-administered measures of quality of life, physical problem
      checklists, and side effect and HIV-related symptom attribution assessments. The
      most prevalent physical problems were fatigue, stiff/painful joints, aching
      muscles, diarrhea, feelings of depression, and neuropathy. Those most commonly
      labeled as side effects of HAART included upset stomach, nausea/vomiting,
      constipation, and changes in taste. Most commonly cited as symptoms related to
      HIV disease were tender lymph nodes, night sweats, weight loss, fever, and loss
      of strength. Impact of side effects, symptoms, and both were associated with
      impaired physical and social functioning. Disease-related symptoms, but not side
      effects, were related to perceptions of general health. Results suggest that HIV
      positive persons taking HAART make distinctions between symptoms of disease and
      side effects of treatment. Perceived disease-related symptoms and side effects
      have significant and unique associations with quality of life. Findings have
      implications for symptom and side effects management, provider relations, and
      future research.

PMID- 14586197
TI  - Close relationships and social support in coping with HIV: a test of sensitive
      interaction systems theory.
AB  - This study tested sensitive interaction systems theory, and examined how persons
      with HIV seek and receive social support in relationships with peers versus
      parents and the association between different kinds of support-receiving
      behaviors and depressive symptoms. The participants were men and women with HIV
      in southeastern Virginia who completed a self-administered questionnaire about
      their relations with parents, an intimate partner, and a close friend.
      Participants reported using more Ask behaviors (a direct form of support seeking)
      with a friend and an intimate partner than with parents. They also reported
      receiving more Approach (Solve/Solace) forms of support from a friend and an
      intimate partner than from parents and less Avoidance (Escape/Dismiss) from a
      close friend than from parents. As a support-seeking behavior Ask was most likely
      to be associated with Approach forms of support providing from all types of
      relationship partners. Avoidance from parents, an intimate partner, or a friend
      was positively associated with depressive symptoms. Counselors should discuss
      with clients the social support process and how different forms of support
      seeking and support providing may be more or less useful in coping with HIV.

PMID- 14586198
TI  - HIV and STD risk behavior among 18- to 25-year-old men released from U.S.
      prisons: provider perspectives.
AB  - Ninety-seven service providers, representing 83 agencies, were interviewed about
      sexual and drug use HIV/STD risk behaviors and their determinants among young men
      who have been released from prison. Providers believed that men frequently
      practiced sexual risk behavior, often in conjunction with substance use.
      Individual determinants of risk behavior primarily focused on "making up for lost
      time," being a man, degree of HIV/STD knowledge and vulnerability, desire to
      escape, and future orientation. Peers, partners, and family were portrayed as
      strong interpersonal influences on risk behavior, both positively and negatively.
      The dominant contextual determinant of risk behavior was the co-occurrence of sex
      and drug use. Structural determinants of reduced risk included stable housing,
      economic sufficiency, and positive community support for safer behavior (e.g.,
      drug treatment access, needle exchange). The findings highlight the need for
      comprehensive, transitional case management for young men as they reintegrate
      into the community, including HIV/STD prevention.

PMID- 14586199
TI  - Asking and telling: communication about HIV status among Latino HIV-positive gay
      men.
AB  - Communication about HIV status--that is, asking about a sex partner's status as
      well as disclosing one's own status--was examined in a sample of 129 Latino HIV
      positive gay men interviewed as part of a larger study conducted in New York,
      Miami, and Los Angeles. Asking and telling were strongly related to each other;
      however, participants were more likely to disclose their positive serostatus to
      sex partners than to solicit information about their partners' serostatus. Region
      of birth was associated with both asking and telling. Participants with bilingual
      friendship networks reported more communication with partners. Higher levels of
      social isolation were related to lower levels of communication, and perceived
      negative consequences--beliefs that disclosure would result in negative
      consequences or rejection--were related to less telling. Contrary to
      expectations, reported experiences of gay discrimination were positively
      associated with communication of serostatus.

PMID- 14586200
TI  - Drug use, increasing incarceration rates, and prison-associated HIV risks in
      Thailand.
AB  - BACKGROUND: Incarceration is a known risk for HIV infection in Thai drug users.
      Through the 1990s, incarceration rates for drug-related offenses rose sharply,
      whereas HIV prevention and drug treatment in prisons remained limited. METHODS:
      We assessed HIV and incarceration risks for injection drug users (IDU) and non
      IDU in a large treatment center cohort in northern Thailand to investigate HIV
      and prison risks in this period. We used Thai Bureau of Corrections data to
      assess incarceration and prevention funds in prisons, 1992-2000. RESULTS: Among
      1,865 drug user in the treatment cohort, 503 (27.0%) had ever been jailed. Men
      (OR 3.3, 95% CI 2.1, 5.2), IDU (OR 6.3, 95% CI 5.1, 7.9), and men who have sex
      with men (MSM) (OR 3.4, 95% CI 1.8, 6.3) were more likely to have been jailed.
      Among male IDU who had ever been jailed (N = 272), 15.8% had used drugs in
      prison. In a multivariate model, incarceration and ever IDU remained
      independently associated with HIV infection; IDU, MSM behaviors, and harmful
      traditional practices remained independently associated with having been jailed.
      From 1992 to 2000, overall alleged narcotics offenses increased from 117,000 to
      276,000/year. The number of persons incarcerated for narcotics offenses increased
      fivefold from 1992 to 1999, from 12,860 to 67,440. For FY 2000, narcotics
      treatment accounted for 0.06% of the Thai corrections budget, whereas HIV
      programs in prisons were 0.017%. CONCLUSIONS: Incarceration rates for narcotics
      offenses have increased sharply in Thailand, whereas prevention has lagged.
      Having been jailed is an important independent risk for HIV infection among Thai
      male drug users, especially IDU and MSM. HIV prevention and drug treatment are
      urgently needed in Thai prisons.

PMID- 14586202
TI  - Perceived condom use self-efficacy among at-risk women.
AB  - The objectives of this study are to assess the confidence in their ability to use
      condoms among at-risk women and identify predictors for the women's condom use
      self-efficacy. Structured interviews were conducted with 250 adult women in
      Atlanta, Georgia, between August 1997 and August 2000. Overall, the women
      reported feeling moderately to moderately-strongly confident in their ability to
      use condoms consistently. Multivariate analysis showed women with higher condom
      use self-efficacy were significantly younger, experienced childhood neglect, had
      higher self-esteem, communicated better with their sex partner, and had fewer
      drug problems. Findings suggest the importance of addressing condom use self
      efficacy in HIV risk reduction programs with a specific focus on women and the
      need to be attuned to tailored needs for specific subgroups such as older women
      or women who encountered childhood neglect.

PMID- 14586201
TI  - Determinants of female and male condom use among immigrant women of Central
      American descent.
AB  - This study was designed to determine factors that influence female and male
      condom use among Central American women, applying the theory of planned behavior.
      A cross-sectional design was employed and a sample of 175 Central American women,
      18-50 years old, was recruited from a community-based clinic in Los Angeles
      County. Participants in this study were interviewed face-to-face. Attitude,
      subjective norm, and perceived behavioral control explained 41% and 45% of the
      variation in the intention to use male and female condoms, respectively.
      Respondents' friends and mothers influenced their subjective norms. Beliefs
      regarding sexual sensation and sexually transmitted infection/pregnancy
      prevention affected respondents' attitudes toward condoms. Trust issues were also
      a major factor affecting attitudes toward female condoms. Condom use and sex
      negotiation skills predicted control over condoms. Results of this study can be
      used to design HIV/AIDS prevention programs that help women feel control over
      condom use and their sexual behavior.

PMID- 14586203
TI  - Models of health-related behavior: a study of condom use in two cities of
      Argentina.
AB  - This study aimed at determining the relative importance of motivational and
      control factors in the prediction of condom use in a high-risk heterosexual
      sample from two cities of Argentina. Participants reported their attitudes,
      norms, control perceptions, intentions, and condom use with regard to main and
      occasional partners. Control perceptions was the main predictor for intentions to
      use condoms and actual condom use with both partners. Furthermore, the norm of
      the partner predicted condom use with the main partner, whereas the norm of
      family and friends predicted condom use with occasional partners. There were no
      differences in condom-use determinants across men and women. Interventions for
      this population should train at-risk heterosexuals to manage the personal and
      interpersonal difficulties of condom use and warn audiences of implicit theories
      that associate love and commitment with perceptions that condom use with main
      partners is unnecessary.

PMID- 14586204
TI  - Multilevel analysis of women's empowerment and HIV prevention: quantitative
      survey Results from a preliminary study in Botswana.
AB  - This preliminary study explored relationships between women's empowerment and HIV
      prevention on the national and individual level with a focus on Botswana. Among
      sub-Saharan Africa countries, HIV prevalence was positively correlated with
      indirect indicators of women's empowerment relating to their education (female
      enrollment in secondary education and ratio of female to male secondary school
      enrollment), but not to their economic status (female share of paid employment in
      industry and services) or political status (women's share of seats in national
      parliament), while controlling for gross national income, percentage of births
      attended, and percentage of roads paved. Condom use at last sexual encounter was
      positively and significantly correlated with both indicators of women's
      educational empowerment, but was not significantly related to the other two
      indices. Empowerment at the individual level was explored through a preliminary
      quantitative survey of 71 sexually active women in Gaborone, Botswana, that was
      conducted in February 2001. Regression analyses showed that women's negotiating
      power and economic independence were the factors most strongly related to condom
      use, and did not show that education was a crucial factor. Economic independence
      was the factor most strongly related to negotiating power. These results suggest
      that in Botswana, HIV prevention efforts may need to improve women's negotiating
      skills and access to income-generating activities.

PMID- 14586205
TI  - Substance use and high-risk sex among people with HIV: a comparison across
      exposure groups.
AB  - Substance use is associated with increased risk for HIV transmission by HIV
      positive people to uninfected partners through sexual contact. The largest risk
      groups for infection, men who have sex with men (MSM) and injecting drug users
      (IDUs), have high rates of substance use, but little is known about their
      substance use post-HIV diagnosis. We compared the prevalence of substance use
      between these two groups and a third group, heterosexual men and women, and
      tested for differential association between substance use and sexual behaviors
      across exposure groups in a national sample of patients in treatment for HIV.
      Substance use was most prevalent among MSM. Substance use and current dependence
      were associated with being sexually active among MSM but not IDUs; marijuana,
      alcohol, and hard drug use were most strongly associated with being sexually
      active among MSM. Whereas substance use predicted high-risk sex, there were few
      differences among exposure groups in these associations.

PMID- 14586207
TI  - Biological role of adduct formation of the ruthenium(III) complex NAMI-A with
      serum albumin and serum transferrin.
AB  - NAMI-A is an innovative ruthenium(III) complex with a very encouraging
      preclinical profile of metastasis inhibition, which is undergoing initial phases
      of clinical trials. To assess the pharmacological relevance of the drug fraction
      associated to plasma proteins, adducts of NAMI-A with either serum albumin or
      serum transferrin were prepared and their biological effects tested in vitro and
      in vivo. Specifically, adducts of NAMI-A with either serum albumin or serum
      transferrin, prepared and characterized at a ruthenium-to-protein molar ratio of
      4:1, were evaluated in vitro on the KB human tumor cell line and in vivo on the
      MCa mammary carcinoma tumor. The effects of NAMI-A/protein adducts on cell
      viability and on cell cycle progression were found to be far smaller than those
      produced by free NAMI-A. GFAAS measurements point out that the amount of
      ruthenium that gets into cells is drastically reduced when NAMI-A is presented in
      its protein-bound form. In vivo use of NAMI-A adducts with albumin and
      transferrin resulted markedly less effective on lung metastasis reduction, than
      free NAMI-A. Overall, the present results suggest that binding to plasma proteins
      causes a drastic decrease of NAMI-A bioavailability and a subsequent reduction of
      its biological activity, implying that association to plasma proteins essentially
      represents a mechanism of drug inactivation.

PMID- 14586206
TI  - In vivo antitumor activity of a novel sulfonamide, HMN-214, against human tumor
      xenografts in mice and the spectrum of cytotoxicity of its active metabolite, HMN
      176.
AB  - The cytotoxic effects of HMN-176 ((E)-4-[[2-N-[4-methoxybenzenesulfonyl] amino]
      stilbazole] 1-oxide; a newly synthesized compound, were evaluated and compared
      with those of the clinically used antitumor agents cis-platinum, adriamycin,
      etoposide, taxol, and vincristine in 22 human tumor cell lines isolated from
      various organs. HMN-176 exhibited potent cytotoxicity with IC(50) values in the
      nM range, and the variance of its cytotoxic efficacy was remarkably small. Drug
      resistant cell lines also showed low cross-resistance to HMN-176 corresponding to
      overall resistance indices of less than 14.3. HMN-214 was synthesized as an oral
      prodrug because of the poor oral absorption of HMN-176 itself. Pharmacokinetic
      studies showed that HMN-214 was an acceptable oral prodrug of HMN-176. In the in
      vivo analysis of the schedule-dependency of HMN-214, the repeated administration
      for over 5 days elicited potent antitumor activity, as expected from the exposure
      dependency of the cytotoxicity of HMN-176 and from the cytometric studies. The
      antitumor activity of HMN-214 against human tumor xenografts was equal or
      superior to that of clinically available agents, including cis-platinum,
      adriamycin, vincristine, and UFT without severe toxicity such as neurotoxicity.
      Because of its good activity in preclinical trials, HMN-214 has entered Phase I
      clinical trials in the USA.

PMID- 14586208
TI  - Quinolizidinyl derivatives of iminodibenzyl and phenothiazine as multidrug
      resistance modulators in ovarian cancer cells.
AB  - The development of multidrug-resistance (MDR) in neoplastic cells is often
      responsible for the therapy failure and poor outcome of a number of human
      cancers. MDR may be associated with the expression of the multidrug transporter
      glycoprotein p170, encoded by the MDR1 gene, which acts as an ATP-dependent
      efflux pump by reducing the intracellular accumulation of some cytotoxic agents.
      A variety of iminodibenzyl and phenothiazine derivatives, characterized by the
      presence of a bicyclic, strongly basic, and highly lipophilic quinolizidine
      nucleus, were synthesized to investigate their ability to modulate the MDR
      phenotype. A set of 10 of them (named 1-10), bearing quinolizidine moiety linked
      through different connecting chains, were tested as chemoresistance-reversing
      agents on doxorubicin-resistant ovarian cancer cells (A2780-DX3). A 51-fold
      resistance to doxorubicin was reported in the A2780-DX3 compared to the parental
      sensitive A2780 WT with mean IC(50) values of 0.02 and 1.02 muM, respectively.
      Moreover, overexpression of the glycoprotein p170 in the resistant cell line was
      detected by Western blot analysis. By cytotoxicity assays and time-course
      experiments, different treatment schedules with resistance modulators (including
      clomipramine as reference drug) and doxorubicin were taken into account. The 16 h
      exposure of cells to 1 muM of modulator before doxorubicin demonstrated to be
      superior in sensitizing the resistant cell line. In particular, compounds 8, 7,
      10, and 4 increasingly potentiated doxorubicin cytotoxicity, up to 5.6-fold in
      A2780-DX3 cells. The present results suggest promising indications for further
      development of these compounds as chemosensitizing drugs.

PMID- 14586209
TI  - Effect of novel benzoylphenylurea derivatives on DNA polymerase alpha activity
      using the synthesome-based in vitro model system.
AB  - Six benzoylphenylurea (BPU) derivatives have been synthesized in Japan and
      extensively evaluated by the U.S. National Cancer Institute. They demonstrated
      potent antitumor activity in vitro against several cancer cell lines as well as
      in vivo against several tumor models. One of these agents, NSC639829, has now
      entered clinical trials. Studies have shown that these compounds are effective
      inhibitors of in vitro tubulin polymerization. The parent compound, NSC624548 (HO
      221), has been shown to inhibit calf thymus DNA polymerase alpha activity. In
      this study we examined the effects of four BPU derivatives (NSC624548, NSC639828,
      NSC639829, and NSC654259) on the activity of the synthesome-associated DNA
      polymerase alpha, Escherichia coli DNA polymerase I, and calf thymus DNA
      polymerase alpha. Among the compounds tested, only NSC624548 and NSC639828
      inhibited the activities of E. coli DNA polymerase I and calf thymus DNA
      polymerase alpha. Excess DNA polymerase I or DNA polymerase alpha dramatically
      reduced the inhibition produced by these compounds. NSC624548 and NSC639828 also
      showed inhibitory effects of the synthesome-associated DNA polymerase alpha
      similar to that produced upon using the purified E. coli and calf thymus enzymes.
      All of the four compounds did not show inhibitory effect on DNA polymerase delta.
      The similar pattern of inhibition these compounds exert on both the purified calf
      thymus and the synthesome-associated DNA polymerase alpha offers further support
      for the validity of the DNA synthesome as a novel in vitro model system for
      studying anticancer drug action.

PMID- 14586210
TI  - A study of a different dose-intense infusion schedule of phenylacetate in
      patients with recurrent primary brain tumors consortium report.
AB  - PURPOSE: To compare two different infusion schedules of phenylacetate (PA) in
      patients with primary brain tumors and to assess the feasibility of the
      administration in a multi-institutional setting. PATIENTS AND METHODS: Adult
      patients with recurrent primary brain tumors were treated with PA on two
      different schedules. The first schedule (I) consisted of a 2-week continuous,
      intravenous infusion followed by a 2-week rest period (14 days on, 14 days off)
      at a dose of 400 mg/kg/day based on ideal body weight. This was repeated once and
      the 8-week period defined as a cycle. The second schedule (II) consisted of a 12
      day continuous infusion at a dose of 400 mg/kg/day based on IBW with a 2-day rest
      period. This was repeated four times for a duration of 8 weeks which defined one
      cycle of therapy. Cycles were repeated until tumor progression, unacceptable
      toxicity, or a delay of more than 28 days from the last day of the preceding
      infusion. Tumor response was assessed every 8 weeks. The National Cancer
      Institute toxicity criteria were used to assess toxicity. Dose adjustments were
      specified for toxicities. Plasma concentrations achieved during the patients'
      first cycle of therapy were assessed. RESULTS: The clinical results of the phase
      II study of patients treated on schedule I were previously reported [8]. Of the
      nine eligible patients treated on schedule II, seven were assessable for
      radiographic response. There were no objective responses. One patient had stable
      disease and six had progressive disease. The median survival was 9 months (95%
      confidence intervals of 3-12 months). The steady state plasma concentrations of
      PA and phenylacetylglutamine were comparatively the same between the two dosing
      schedules. However a 1.7-fold greater amount of PA was delivered by schedule II.
      CONCLUSION: The infusions were well tolerated. Despite the feasibility of
      administering this agent in an outpatient setting, there were no responses seen
      with the more intensive schedule of PA.

PMID- 14586211
TI  - Weekly regimen of irinotecan/docetaxel in previously treated non-small cell lung
      cancer patients and correlation with uridine diphosphate glucuronosyltransferase
      1A1 (UGT1A1) polymorphism.
AB  - PURPOSE: Inherited variations in drug metabolizing enzymes may influence drug
      efficacy. This phase II study assesses the impact of second-line weekly
      irinotecan (CPT-11)/docetaxel in non-small cell lung cancer (NSCLC) patients, and
      gauges the uridine diphosphate glucuronosyl transferase (UGT1A1) polymorphism
      influence in toxicity and antitumor activity. EXPERIMENTAL DESIGN: Fifty-one
      patients with NSCLC treated with at least one prior chemotherapy regimen were
      enrolled. Patients received irinotecan 70 mg/m(2) followed by docetaxel 25
      mg/m(2). Both drugs were given on days 1, 8, and 15 every 28 days. UGT1A1
      polymorphism were analyzed in blood samples of 47 patients. The UGT1A1
      polymorphism are classified according to the number of TA repeats in the promoter
      region of this gene. RESULTS: Three patients (6%) achieved a partial response and
      nineteen patients (37%) had stable disease. Median survival was 8 months (95% CI:
      4.8-11.2) and 1-year survival 30%. Grade 3-4 hematologic toxicity was low (less
      than 10% of patients); 15% of patients had grade 3 asthenia and 25% of patients
      had grade 3/4 diarrhea. The frequency of UGT1A1 genotypes was as follows: 6/6
      49%, 6/7 36%, and 7/7 15%. No differences in toxicity were observed according to
      UGT1A1 polymorphism. A nonsignificant improvement in time to progression (4 vs. 3
      months) and median survival (11 vs. 8 months) was detected in patients with the
      variant alleles (6/7 and 7/7). CONCLUSIONS: This weekly irinotecan/docetaxel
      regimen has shown an acceptable toxicity profile while encouraging median and 1
      year survival in heavily pretreated NSCLC patients. The tendency to better
      prognosis in patients carrying the variant genotypes 6/7 and 7/7 of UGT1A1 gene
      requires further validation.

PMID- 14586213
TI  - A randomized phase II evaluation of bryostatin-1 (NSC #339555) in persistent or
      recurrent squamous cell carcinoma of the cervix: A Gynecologic Oncology Group
      Study.
AB  - OBJECTIVES: The Gynecologic Oncology Group performed a randomized phase II study
      to determine the antitumor activity and toxicity of two different schedules of
      administration of bryostatin-1 in patients with persistent or recurrent squamous
      cell carcinoma of the cervix. METHODS: Eligible patients were randomized to
      receive either bryostatin-1 25 mug/m(2) as a 1-h infusion weekly for 3 weeks
      followed by a 1-week rest (Regimen I) or bryostatin-1 120 mug/m(2) as a 72-h
      continuous infusion every 2 weeks (Regimen II). RESULTS: A total of 70 patients
      were enrolled on this study. There were 32 eligible patients on Regimen I and 33
      eligible patients on Regimen II; all but 4 had had prior chemotherapy. There were
      two partial responses (one on each treatment arm) among the 65 eligible patients
      (response rates = 3.1 and 3.0%, respectively). Ten patients on each regimen had
      stable disease. The most common adverse event was myalgia; 8 of 32 patients (25%)
      on Regimen I and 16 of 33 patients (48%) on Regimen II had any grade of myalgia.
      There was no significant myelosuppression on either treatment arm. CONCLUSIONS:
      Both of these schedules and doses of bryostatin-1 are inactive as single agents
      in the second-line treatment of squamous cell carcinoma of the cervix.

PMID- 14586212
TI  - Pharmacokinetics and safety of ILX23-7553, a non-calcemic-vitamin D3 analogue, in
      a phase I study of patients with advanced malignancies.
AB  - PURPOSE: Differentiation therapy is an alternative to chemotherapy with
      potentially less toxicity, improved quality of life, and survival. We conducted a
      phase I trial of ILX23-7553, a formulation of 1,25-dihydroxy-16-ene-23-yne
      vitamin D(3), a 1,25-dihydroxyvitamin D(3) analog with preclinically demonstrated
      antitumor and differentiating effects and diminished hypercalcemic effects.
      PATIENTS AND METHODS: The protocol consisted of five daily oral treatments during
      14-day cycles at 15 dose levels from 1.3 to 45.0 mug/m(2)/day. We treated 42
      heavily pretreated patients who had a variety of malignancies with 162 treatment
      cycles, and obtained pharmacokinetics from three patients at the two highest dose
      levels. RESULTS: There were no grade 3 or 4 toxicities. Grade 1-2 toxicities
      included diarrhea, nausea, fatigue, constipation, and one grade 1 hypercalcemia.
      Average day 6 calcium was 9.26 +/- 0.55 mg/dl in cycle 1 and 9.30 +/- 0.67 mg/dl
      in cycle 2. Pharmacokinetics at dose levels 14 (40 mug/m(2)/day) (1 patient) and
      15 (45 mug/m(2)/day) (2 patients) demonstrated an average C(max) of 30.4 +/- 7.8
      pg/ml (0.07 nM) and 104 +/- 38.2 pg/ml (0.25 nM), and AUCs of 222.5 +/- 225.2
      pg.h/ml and 855 +/- 536 pg h/ml, respectively. Eight patients (19%) had stable
      disease. While in vitro effects have been reported at these concentrations, they
      were at least 10-fold lower than ED(50)s, and the study was terminated before an
      MTD was reached. CONCLUSION: The drug is safe and has potential benefits at serum
      concentrations where effects begin to be noted in vitro. Further study is needed
      with a reformulated higher unit dose compound to determine the safety and
      efficacy of higher serum concentrations.

PMID- 14586214
TI  - Activity of weekly irinotecan (CPT-11) in patients with advanced non-small cell
      lung cancer pretreated with platinum and taxanes.
AB  - Irinotecan (CPT-11), a semisynthetic derivative of camptothecin, is active in the
      treatment of non-small cell lung cancer (NSCLC). In this report we describe our
      experience with this drug when used as a single agent in patients with advanced
      NSCLC refractory to chemotherapy with platinum and taxanes. Nineteen NSCLC
      patients (thirteen males and six females; 53% adenocarcinoma and 26% squamous
      cell carcinoma) with a median age of 52 years (range 34-71) and a Karnofsky
      performance status of 60% (60-80%) were included in the study. At baseline, the
      patients had a median of two disease sites and had been treated with a median of
      two prior regimens. Irinotecan was given at a dose of 100 mg/m(2) i.v.) weekly
      for 4 weeks followed by 1 week of rest. A total of 123 weekly infusions were
      administered, and each patient received a median of 4 weeks of treatment (range 1
      32). All patients were evaluated by intention-to-treat analysis for efficacy and
      safety. Main toxicities reported were grade 3 neutropenia (10% of patients),
      diarrhea (10% of patients), and grade 4 thrombocytopenia (5% of patients). The
      overall clinical response rate was 16% (95% CI: 8-24) with three partial
      responses and 9 (47%) patients with stable disease. The median time to
      progression and the median survival time were 7 and 15 weeks, respectively. In
      conclusion, weekly irinotecan showed antitumoral activity and minimum toxicity in
      NSCLC patients refractory to platinum and taxanes.

PMID- 14586215
TI  - A phase II study of rebeccamycin analog (NSC-655649) in metastatic renal cell
      cancer.
AB  - OBJECTIVE: Rebeccamycin analog (NSC-655649) is an antibiotic with antitumor
      properties demonstrated in preclinical and phase I studies. We conducted a phase
      II trial to evaluate the efficacy and toxicity of this agent in patients with
      advanced renal cell cancer (RCC). METHODS: Eligible patients had histologically
      or cytologically confirmed diagnosis of RCC that was either locally advanced
      unresectable, locally recurrent, or metastatic. Patients had to have measurable
      disease, no prior chemotherapy, life expectancy of greater than 12 weeks, an
      Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, adequate
      organ function, and be >/=18 years old. Patients were treated with NSC-655649 at
      a dose of 165 mg/m(2) daily i.v. over 30-60 min for 5 days. Treatment was
      repeated every 21 days. Response was assessed every two courses. RESULTS: Twenty
      four patients were enrolled. There were sixteen males and eight females with a
      median age of 60.5 years (range 42-76). Nineteen were Caucasians, seventeen had
      prior nephrectomy, and thirteen had prior immunotherapy. The major toxicity was
      myelosuppression with grade 3 and 4 neutropenia in 38% of patients and anemia in
      33% of patients. There were two partial responses (2/24, 8%) and 11 patients
      (46%) achieved stable disease (SD). The 6-month progression-free rate for
      patients with SD was 30%. Of the seventeen patients with progressive disease at
      registration, one had a PR and eight had SD. The overall median survival time for
      all 24 patients was 10.0 months (90% CI=5.2, 17.4 months). The 12-month survival
      rate was 39%, with 90% CI=(0.21, 0.58). Nine patients are still alive with
      survival times ranging from 3.8 to 24.2 months, at a median follow-up time of
      11.9 months. CONCLUSION: Rebeccamycin analog (NSC-655649) is well tolerated and
      has modest antitumor activity in patients with advanced RCC.

PMID- 14586216
TI  - A phase II study of topotecan in patients with anaplastic oligodendroglioma or
      anaplastic mixed oligoastrocytoma.
AB  - To determine the efficacy and toxicity of a novel chemotherapeutic approach with
      topotecan, a camptothecin analog, for progressive or recurring anaplastic
      oligodendroglioma or mixed oligoastrocytoma.Patients from seven centers with
      recurrent or progressive disease were treated with topotecan, 1.5 mg/m(2)
      intravenously (i.v.), 30 min dailyx5 days every 3 weeks. Efficacy and toxicity
      were assessed clinically and radiologically. The study was planned to accrue up
      to 30 evaluable patients if there was at least one response among the first 15
      patients treated. Sixteen eligible patients entered the study. No response was
      documented in 14 evaluable patients. Eleven patients had stable disease of a
      median of 3.8 months and three had progressive disease. Sixteen patients were
      evaluable for toxicity. The most significant toxic effect was myelosuppression.
      Grade 3 or 4 granulocytopenia was experienced by 15 of 16 patients and led to
      dose reduction in nearly half of the cycles delivered. Other adverse effects were
      fatigue, nausea, stomatitis, alopecia, and vomiting.Topotecan, delivered in the
      dailyx5 regimen, is relatively well tolerated. We could not demonstrate
      significant activity among the population studied to justify completing accrual
      to 30 patients. Topotecan did not demonstrate, with this small sample size,
      efficacy as a salvage chemotherapy monotherapy after exposure to procarbazine,
      CCNU and vincristine. Further trials with different agents in this indication are
      certainly warranted.

PMID- 14586217
TI  - An open label, non-comparative phase II study of topotecan as salvage treatment
      for patients with soft tissue sarcoma.
AB  - BACKGROUND: The number of effective cytotoxic agents for the treatment of
      patients with metastatic soft tissue sarcoma (STS) is limited, especially when
      patients have failed anthracyline-based chemotherapy. PATIENTS AND METHODS:
      Between 1999 and 2000 a total of 16 patients with histologically proven STS
      progressing during or after first-line anthracycline-based chemotherapy were
      entered into this open-label, noncomparative study. Topotecan was administered as
      a 30-min infusion at a dosage of 1.5 mg/m(2) on five consecutive days every 3
      weeks. All patients had received an anthracycline- or ifosfamide-based first-line
      chemotherapy. RESULTS: None of the 16 included patients achieved an objective
      response to topotecan. Six patients achieved stable disease (38%), lasting for at
      least 6 weeks in four patients (25%) and for less than 6 weeks in two patients
      (13%). Ten patients (62%) had progressive disease. The median time to progression
      was 79 days calculated from the start of topotecan therapy (range, 28-230). The
      treatment was well tolerated; however, both anemia and thrombopenia grade III/IV
      occurred in 25% of the patients as well as severe neutropenia in 69% of the
      patients. Nonhematologic toxicities grade III/IV such as diarrhea and severe
      bleeding occurred only in one patient each (6%). DISCUSSION: Topotecan is well
      tolerated in anthracycline-resistant patients with metastatic STS, but no
      objective response has been observed in this trial.

PMID- 14586219
TI  - [Optimizing microbiological controls of corneal organ culture media].
AB  - BACKGROUND/AIMS: To compare the efficiency of an automated method using blood
      bottles with conventional microbiological tests for controlling sterility in
      cornea organ culture media. METHODS: Two complementary studies were conducted.
      Experimental study: standard organ culture media were contaminated with four
      different inocula of 14 bacteria and 3 fungi. The bactericidal activity of organ
      culture media were evaluated after 48 hours of incubation at 31C. Observational
      study: 357 samples of organ culture media were collected over 1 year in our
      cornea bank. For both studies, media were inoculated in three blood bottles
      (aerobic, anaerobic, fungal) placed in an automat with automated detection every
      10 minutes, and in three conventional microbiological media as a control. Changes
      in organ culture medium color and growth on conventional broth were checked daily
      by visual inspection. All samples were observed experimentally for 14 days. The
      sensitivity and rapidity of contamination detection were compared across the
      three methods: blood bottles, conventional method, and visual inspection of
      medium color. RESULTS: Experimental study: organ culture medium eradicated five
      bacteria: S. pneumoniae, B. catarrhalis, E. coli, P. acnes and H. influenzae. For
      the others, (Methicillin-resistant S. aureus, Methicillin-sensitive S. aureus, S.
      epidermidis, S. haemolyticus, P. aeruginosa, A. baumannii, B. subtilis, K.
      pneumoniae, E. faecalis, C. albicans, C. kruzei, A. fumigatus) the blood bottle
      method, the conventional microbiological method, and the visual inspection
      detected microbiological growth respectively in 100%, 76.5%, and 70% of cases.
      Mean detection time using blood bottles was 15.1 hours (standard deviation, 13.8;
      range, 2-52). In cases of detection by the blood-bottle method and the
      conventional method, the former was always faster: 95.5% versus 65.2% detection
      within 24 hours (p=0.022). Observational study: the global contamination rate was
      8% (29/357 analysis). The gain in sensitivity with blood bottles was 25% compared
      with the conventional method. Five bacteria (three coag. neg Staphylococcus, one
      E. faecalis, one P. paucimobilis) were detected only by the blood bottles. In
      addition, these were always detected more quickly with, respectively, 66.6%
      versus 26.6% detection with 24 hours (p=0.028). CONCLUSIONS: Blood bottles detect
      contaminations of cornea organ culture media more efficiently and faster than
      conventional microbiological methods. They make it possible to reduce the
      quarantine period with an equally high security level. Consequently, they should
      be recommended in cornea preservation guidelines.

PMID- 14586218
TI  - [Flow cytometric analysis of HLA-DR, IL-6 and IL-8 expression by conjunctival
      epithelial cells from patients with prolonged topical antiglaucoma treatments].
AB  - AIM OF THE STUDY: To investigate the expression of three inflammation markers,
      HLA-DR, IL-6, and IL-8, by conjunctival epithelial cells obtained using
      impression cytology (IC) samples from long-term treated glaucoma patients.
      PATIENTS AND METHODS: IC samples were obtained from the 60 following individuals:
      45 patients suffering from primary open-angle glaucoma and receiving topical
      treatments for at least 1 year and 15 subjects with no ophthalmological disease
      (controls). Membrane expression of HLA-DR and intracellular expression of IL-6
      and IL-8 were quantified, respectively, by indirect and direct immunofluorescence
      techniques. Fluorescence levels were quantified using calibrated fluorescent
      beads. RESULTS: The percentage of HLA-DR-positive cells was significantly higher
      on IC samples from multitreated glaucoma patients and from patients treated by
      either preserved betablocker or preserved prostaglandin analogue than on IC
      samples from control individuals. Interestingly, the percentage of HLA-DR
      positive cells was not significantly increased upon treatment with unpreserved
      betablocker. However, the percentage of IL-6- and IL-8-positive cells as well as
      IL-6 and IL-8 expression levels was significantly higher in patients than in
      controls, regardless of the treatment type and the presence of preservative. A
      significant positive correlation was found between HLA-DR and cytoplasmic IL-6
      expression, between HLA-DR and cytoplasmic IL-8 as well as between IL-6 and IL-8
      cytoplasmic expressions. CONCLUSION: The present study confirms that there is an
      increased expression of HLA-DR in treated glaucoma patients compared to controls
      and demonstrates that antiglaucoma treatments lead to increased IL-6 and IL-8
      expressions. It also indicates that benzalkonium-preserved eyedrops and preserved
      multitherapy may induce stronger inflammatory responses than do unpreserved
      eyedrops, although further studies are needed to determine the respective
      inflammatory role of preservative and therapeutic molecules. In this study, flow
      cytometry was used to detect the intracellular pro-inflammatory cytokines in
      conjunctival cells obtained by impression cytology. This standardized and
      reliable technique was a useful tool to assess inflammatory and allergic ocular
      surface disorders.

PMID- 14586220
TI  - [Adult cataract surgery in Aquitaine: motivations, technical procedures and
      results. Inventory in 1999].
AB  - PURPOSE: Cataract surgery in the Aquitaine department in France has been
      investigated in terms of motivations, technical procedures, and results. METHODS:
      Observations were made from a retrospective sample of 500 operations performed
      during the last 3 months of 1999. Information was collected concerning patient
      motivation, the technical aspects of the operation, inpatient or outpatient
      management, the major follow-up events and the functional results. RESULTS: The
      study showed substantially altered visual function in most of the patients before
      the operation, very few preliminary technical investigations, a
      phacoemulsification procedure in 97% of the cases, and 95% good or very good
      results. Outpatient surgery was performed in 33% cases, comparable to the 23%
      average in France over the same period of time. Two cases of endophthalmia were
      diagnosed and successfully treated. Secondary cataract appeared in 16 patients
      during the 6-month follow-up period. CONCLUSION: These results show that
      practices in Aquitaine comply with current standards. They suggest that all the
      components necessary to further development of cataract surgery are in place, as
      long as the surgical supply is able to respond to the increasing demand.

PMID- 14586221
TI  - [Intraocular pressure results of contact transscleral cyclophotocoagulation with
      Neodymium YAG laser for refractory glaucoma].
AB  - PURPOSE: To evaluate the effects of contact transscleral cyclophotocoagulation
      with neodymium YAG laser for refractory glaucoma. METHOD: This was a
      retrospective study with 36 patients (37 eyes) who were treated at the Rouen
      Hospital from February 1996 to February 2001. Patients had various types of
      glaucoma: glaucoma in pseudophakia (12), primary open-angle glaucoma (16),
      posttraumatic glaucoma (6), glaucoma associated with uveitis (4), neovascular
      glaucoma (3), and glaucoma after silicone oil (1). The Neodymium YAG laser
      (Alcon) was used for treatment. Energy was delivered in up 32 applications of 7-9
      W for 0.7 seconds each. All patients except one 10-year-old child received
      retrobulbar anesthesia. Intraocular pressure was measured after 4 hours, 1 month,
      and 10 years. RESULTS: The mean preoperative intraocular pressure of 30.3 (+/
      1.3) mmHg decreased to 19.4 (+/-2) mmHg at 1 month and to 22.2 (+/-2.4) mmHg at 1
      year. Seven patients underwent a second treatment during the year, since the
      first one was insufficient. Treatment lowered the number of medications used to
      decrease intraocular pressure from a pretherapy mean of 2.7 mmHg to 1.8 mmHg at 1
      month and 2.07 mmHg at 1 year. In three patients who were treated for a painful
      sightless eye, the treatment failed. DISCUSSION: Neodymium YAG laser necroses
      ciliary bodies. Treatment must be dosed to achieve the greatest efficacy without
      hypotonia, although hypotonia is rare, as is non-response to treatment. A few
      patients will be retreated during the year. The subgroup of sightless painful
      eyes had a high failure rate (75%), with half undergoing evisceration. We found
      no other differences according to the origins of refractory glaucoma. CONCLUSION:
      Midterm results of contact transscleral cyclophotocoagulation with Neodymium YAG
      laser are encouraging in the treatment of refractory glaucoma.

PMID- 14586223
TI  - [Air bags and eye injuries: chemical burns and major traumatic ocular lesions--a
      case study].
AB  - The authors report a case of bilateral eye lesions with extended visual sequelae
      after the inflation of a driver's airbag during a head-on collision. The
      superficial facial lesions were accompanied by bilateral eye lesions, reaching
      both the anterior and posterior segments. Bilateral periorbital palpebral
      hematomas; voluminous bipalpebral edema combined with severe -conjunctival edema,
      corneal erosions, and edema; bilateral hyphema; pupillary changes with multiple
      iris sphincter breaks and weak pupillary light reflex only on the right eye;
      retrocession of the iridocorneal angle; and on fundus examination both retinas
      had posterior and peripheral hemorrhages and Berlin retinal edema. Five years
      after the trauma and 4 years after posttraumatic surgery for cataract that had
      progressively appeared on the left eye, the visual acuity is 25/20 in both eyes
      notwithstanding a small paracentral scotoma related to a break in the Bruch
      membrane. A review of the literature shows several types of ophthalmological
      lesions related to the airbag mechanism, which after combustion of an alkaline
      powder inflates at a very high speed, resulting in a risk of corneal-conjunctive
      palpebral alkaline burns added to an eye contusion, which may be responsible for
      severe lesions. The American studies distinguish three factors affecting the
      seriousness of these airbag accidents: (a) wearing glasses, (b) position and size
      of the driver, and (c) inflation force of the airbag. Wearing a seatbelt is
      mandatory to minimize the violence of the oculofacial impact. After facial trauma
      from an airbag, an ophthalmological examination is necessary to assess of the
      chemical burns of the tissues exposed to the alkaline powder and possible major
      ocular lesions.

PMID- 14586222
TI  - [Experimental branch vein occlusion: the effect of carbogen breathing on
      preretinal PO2].
AB  - PURPOSE: To evaluate the variations in preretinal PO2 in normal and in ischemic
      postexperimental branch vein occlusion (BRVO) retinal areas during normoxia,
      hyperoxia (100% O2) and carbogen (95% O2, 5% CO2) breathing. METHODS: Preretinal
      PO2 measurements were obtained in intervascular retinal areas far from the
      retinal vessels of 13 anesthetized miniature pigs with oxygen-sensitive
      microelectrodes (10 microm tip diameter) introduced through the vitreous cavity
      by a micromanipulator. The microelectrode tip was placed at 50 microm from the
      vitreoretinal interface in the preretinal vitreous. PO2 was measured continuously
      for 10 minutes in systemic normoxia, hyperoxia (100% O2 breathing) and carbogen
      (95% O2, 5% CO2) breathing. A BRVO was induced with an argon green laser, and
      oxygen measurements were repeated in normoxia, hyperoxia and carbogen breathing.
      RESULTS: In hyperoxia, preretinal PO2 remained almost constant in both normal
      retinas (DeltaPO2=1.33 mmHg +/- 3.39; n=13) and ischemic retinas (DeltaPO2=3.73
      mmHg +/- 2.84; n=8), although systemic PaO2 significantly increased. Carbogen
      breathing induced a significant increase in systemic PaO2 and PaCO2. Furthermore,
      it significantly increased preretinal PO2: DeltaPO2=23.05 mmHg +/- 17.06 (n=12)
      in normal retinas, and DeltaPO2=22.54 mmHg +/- 5.96 (n=6) in ischemic retinal
      areas. CONCLUSIONS: Systemic hyperoxia does not increase preretinal PO2
      significantly in normal and ischemic post-BRVO retinal areas of miniature pigs,
      as hyperoxia induces a decrease in the retinal blood flow. Carbogen breathing
      significantly increases preretinal PO2 in normal and in ischemic post-BRVO
      retinal areas. This effect is probably due to the vasodilatation of the retinal
      arterioles induced by the intravascular PaCO2 increase.

PMID- 14586224
TI  - [Corneal ring segments (INTACS) for the treatment of asymmetrical astigmatism of
      the keratoconus. Follow-up after 2 years].
AB  - OBJECTIVE: To evaluate the use of corneal ring segments (INTACS) for the
      treatment of asymmetrical astigmatism in keratoconus. MATERIAL AND METHODS: This
      prospective study involved nine eyes of seven patients who were operated on
      between December 1998 and June 2000. A case of keratoconus with opacified cornea
      was excluded from this study. The patients chosen were contact lens-intolerant.
      The surgical intervention was carried out under topical anesthesia. The INTACS
      (Addition Technology) corneal ring insert was inserted approximately 68% of the
      peripheral corneal depth and was centered to the cone of the cornea. RESULTS: No
      intraoperative complications occurred. We noted a flattening of the central
      cornea and a decrease in irregular astigmatism for all patients. Mean
      preoperative uncorrected visual acuity was less than 1/10. Postoperatively two
      eyes had an uncorrected visual acuity of 10/10, seven eyes showed an improvement
      from an uncorrected visual acuity of 2/10 to 7/10. CONCLUSION: We have observed
      that the flattening effect of INTACS inserts on the soft corneal keratoconic
      tissue and on the high astigmatic tissue seems greater than that produced in
      normal cornea. Implantation of INTACS resulted in a significant reduction in
      asymmetrical astigmatism of the keratoconus.

PMID- 14586225
TI  - [Results of inferior oblique muscle surgery in superior oblique paralysis].
AB  - The aim of this study was to evaluate the results of inferior oblique muscle
      recession in certain cases of superior oblique paralysis. Twenty-three patients
      with moderate hyperaction of the inferior oblique muscle, secondary to paralysis
      of the superior oblique muscle, in whom a recession of the ipsilateral inferior
      oblique was applied were enrolled in this study. These cases were selected among
      those with congenital superior oblique paralysis and infantile nontraumatic
      paralysis and those of unknown origin. Isolated recession of the inferior oblique
      muscle achieved a mean decrease in 8.69 +/- 2.05 D in hypertropia in the primary
      position. In 19 cases out of 23 (82.6%) who received isolated recession of the
      inferior oblique muscle, a vertical deviation equal to or less than 4 PD was
      obtained, showing the efficacy of this method in the surgical treatment of the
      cases with superior oblique paralysis and a moderate inferior oblique
      hyperaction.

PMID- 14586226
TI  - [Posterior subcapsular cataract in a case of ulcerative colitis treated with
      corticosteroid enema].
AB  - We report the case of a 65-year-old patient suffering from a long-term ulcerative
      colitis treated with corticosteroid enema and presenting a bilateral posterior
      subcapsular cataract. As far as we know, this is the first case report of steroid
      induced cataract after intrarectal corticosteroid use. Alternative hypotheses
      concerning the mechanism of cataract formation are suggested. This case report
      should warn ophthalmologists and gastroenterologists about the cataractogenic
      effects of corticosteroid enema to ensure that information is provided for
      patients suffering from ulcerative colitis.

PMID- 14586227
TI  - [Toxoplasma gondii and necrotizing retinitis: a case report].
AB  - Toxoplasmic retinochoroiditis is an important opportunistic retinal infection in
      immunodeficiency and elderly patients. The diagnosis of toxoplasmic
      retinochoroiditis is based primarily on characteristic ocular findings, with
      supportive serological evidence. It may present as diffuse necrotizing retinitis
      instead of a focal lesion. We report the original case of a 74-year-old woman who
      presented with blurred vision in her left eye lasting 3 months. In her medical
      history, the patient described a tuberculous infection evolving for some months,
      as well as agranulocytosis treated with Rifadine. Fundus examination revealed
      diffuse necrotizing retinitis, mainly at the nasal quadrant, with marked
      vitreitis in the left eye. Clinical recognition of atypical presentations is
      critical for timely antiparasitic drug therapy. This case initially was
      misdiagnosed as acute retinal necrosis syndrome. The correct diagnosis was
      confirmed by response to polymerase chain reaction studies of an intraocular
      specimen and histopathological analysis. The extensive necrotizing retinitis was
      nonhemorrhagic but associated with retinal detachment. Significant visual loss
      accompanied the infection. Toxoplasmosis should be considered as a cause of
      diffuse necrotizing retinitis in elderly and immunosuppressive patients. Older
      patients may be more susceptible to severe ocular Toxoplasma infections because
      of age-related decline in cell-mediated immunity and chronic underlying diseases.

PMID- 14586228
TI  - [Loss of visual acuity due to choroidal ischemia in Fabry's disease].
AB  - We report a case of a 21-year-old man with Fabry's disease who presented with a
      sudden decrease in visual acuity to 20/200 in the left eye. Pale areas with a
      lobular choroidal distribution were seen on fundus examination. No retinal
      vascular causes were found on further evaluation. With anticoagulation treatment,
      the patient's subsequent course was good, with visual recovery to 20/25 and
      normalization of the funduscopic appearance. Recovery of both visual acuity and
      the pale, lobular areas suggested a choroidal etiology, probably ischemic because
      of the sudden onset. Choroidian ischemia is therefore a cause of visual acuity
      loss in Fabry's disease, so far not described in the literature.

PMID- 14586231
TI  - [Indocyanine green angiography in age-related macular degeneration].
AB  - Indocyanine green ocular angiography was developed more than 30 years ago, but
      has been used commonly for less than 10 years. In exudative age-related macular
      degeneration, certain cases of occult neovascularization may be converted into
      well-defined cases, in theory allowing treatment of more patients.
      Neovascularization is observed as either focal hyperfluorescence (hot spot) or
      diffuse hyperfluorescence (plaque). Scanning laser ophthalmoscopy imaging allows
      for better visualization of feeder vessels, allowing even more selective
      treatment. Even though a multicentric, prospective, randomized study has not yet
      been conducted, a number of pilot studies are very encouraging concerning
      indocyanine green angiography-guided laser treatment.

PMID- 14586229
TI  - [Posterior scleritis: six case reports].
AB  - PURPOSE: To study the clinical features, management guidelines, and the course of
      the disease in six patients with posterior scleritis. SUBJECTS AND METHODS: Six
      patients with posterior scleritis were enrolled in this retrospective study. All
      patients underwent a complete ophthalmic examination, fluorescein angiography,
      and B-scan ultrasonography. Systemic evaluation included physical examination and
      laboratory screening investigations. Medical management included systemic
      indomethacin (two cases), oral steroids (two cases), intravenous pulses of
      methylprednisolone followed by tapered oral steroids (two cases). One patient
      underwent immunosuppressive therapy (azathioprine) because of steroid dependence.
      RESULTS: The main presenting symptoms were pain (six cases) and decreased vision
      (four cases). Chorioretinal changes included chorioretinal folds (six cases),
      retinal folds (five cases), optic disc edema (five cases), serous retinal
      detachment (two cases), and a subretinal mass (one case). Ultrasonography
      disclosed sclerochoroidal thickening in all cases and retrobulbar edema in three
      cases. Systemic evaluation was unremarkable in five cases and revealed Behcet's
      disease in one case. All patients showed a good response to medical treatment.
      CONCLUSION: Posterior scleritis has protean manifestations and can be easily
      overlooked. This diagnosis must be considered in all inflammatory and painful
      ocular disorders with no obvious etiology. B-scan ultrasonography is the most
      useful diagnostic tool in such patients. The disease usually shows a good
      response to systemic anti-inflammatory therapy.

PMID- 14586232
TI  - [Dynamic phototherapy: treatment and retreatment criteria].
AB  - Exudative age-related macular degeneration (ARMD) is benefiting at present from
      new therapeutic approaches. Randomized clinical trials have demonstrated the
      efficacy of photodynamic therapy (PDT) in stabilizing visual acuity at 3 years.
      The basis of PDT consists in activating a photosensitizer with an adapted laser
      wavelength. Functional results are obtained on the basis of a strict
      classification of type of the new vessels responsible for exudative ARMD, based
      on fluorescein angiography. Thus, subfoveal lesions, in the form of either
      predominantly classic (visible new vessels>50%) or occult choroidal
      neovascularization (CNV), are the only indication for this therapy. Classic
      juxtafoveal CNV, where laser photocoagulation thermal burns may extend into the
      foveola, may be an extension of the indication of PDT. The follow-up after PDT is
      based on fluorescein angiography findings. The extension and persistence of
      leakage from the CNV remains an indication for retreatment. Ongoing studies are
      evaluating a number of features in order to define the responder group and
      possibly simplify the retreatment indications.

PMID- 14586233
TI  - [The role of surgery in the treatment of age-related macular degeneration].
AB  - The place of surgery in DMLA amounts to the surgical treatment of choroidal
      neovascular membranes and submacular hemorrhage. After a brief historical review,
      the different techniques currently used are described, but indications have
      become rarer since the development of dynamic phototherapy. However, despite a
      high complication rate, these surgical methods should not disappear from our
      therapeutic arsenal because they have proved their ability to restore good visual
      acuity.

PMID- 14586234
TI  - [Alternative therapies for choroidal neovessels resulting from age-related
      macular degeneration].
AB  - Classic neovessels (CNVs) identified on fluorescein angiography may benefit from
      thermal laser photocoagulation when sparing the fovea. If they extend into it,
      photodynamic therapy may halt the natural progression to a central scotoma.
      Occult CNVs, when subfoveal, may benefit from photodynamic therapy when isolated
      (not associated with classic CNV or with a pigment epithelium detachment). A
      number of therapeutic approaches are being evaluated in order to diversify the
      therapeutic choices available for treatment of CNVs. Transpupillary
      thermotherapy, which causes a limited increase in retinal temperature, could
      produce a sclerosis of occult isolated CNV. This approach has shown interesting
      results in pilot studies but also carries a risk for iatrogenic effects. The
      American randomized clinical trial currently under way will provide an evaluation
      of this treatment. An antiangiogenic therapy currently in progress is studying
      anecortave acetate and another is investigating anti-VEGF compounds. Anecortave
      acetate, which demonstrated its angiostatic activity in experimental models as
      well as in a phase II study, is now in a worldwide randomized clinical trial. The
      anti-VEGF molecules (antibodies and oligonucleotides) have shown very interesting
      preliminary results and are being evaluated in a large number of patients.
      Finally, a preventive therapy consisting of oral supplementation with
      antioxidants (vitamins C, E, and A) and zinc is a major step forward, providing
      the possibility of a real and effective prevention of the complications of age
      related maculopathy.

PMID- 14586237
TI  - [Corneal edema in pseudophakia. A case report].
AB  - Pseudophakic bullous keratopathy is one of the most common complications of
      intraocular lenses, which explains the high rate of this condition in series of
      patients experiencing corneal grafts. It is caused by irreversible damage to the
      endothelial layer of the implanted eye involving the artificial lens, and occurs
      either during cataract extraction or after the operation. Intraoperative
      endothelial protection and the choice of an appropriate lens may contribute to
      decreasing this secondary disease, which can have severe consequences for many
      patients whose corneal graft may not restore their visual potential as well as
      expected. We report a clinicopathological case of a 59-year-old male, previously
      operated on for cataract in both eyes with an anterior chamber lens. A bilateral
      corneal edema occurred a few years after the operation, with a bilateral decrease
      in vision as a consequence. A corneal graft was performed in 2000 on the left eye
      in order to improve the patient's visual autonomy. The best treatment of this
      condition remains prevention, avoiding the use of this type of intraocular lens,
      whose main complication is corneal edema.

PMID- 14586238
TI  - [Endoscopy and surveillance of Barrett's esophagus].

PMID- 14586239
TI  - [Home parenteral nutrition: a continuous challenge].

PMID- 14586240
TI  - [Early closure of temporary stoma of the small bowel].
AB  - AIM: Transient small bowel stoma is usually closed 9-12 weeks after initial
      operation (late closure). Since these stoma have a poor physiological and
      psychological impact with frequent social consequences, we wanted to estimate
      feasibility and results of early closure of small bowel stoma. PATIENTS AND
      METHOD: From January 1998 to December 2001, 39 patients (21 women and 18 men,
      mean age: 64 years) with a transient small bowel stoma were elected for early
      closure. Early closure was performed only if the patient was in good condition,
      and without developing wound or general sepsis. In the other patients, the stoma
      was closed in the usually recommended delay (> 8 weeks). Fifteen patients had an
      early closure of their stoma in a mean delay of 10.0 +/- 0.8 days after the
      initial procedure. Twenty-four patients had a late closure of their stoma in a
      mean delay of 11.4 +/- 3.7 weeks. RESULTS: There were no postoperative deaths and
      no intestinal fistula. Four (10%) wound abscesses occurred and were managed
      without any surgical procedure, 3 in the early closure group (20%) and 1 in the
      late closure group (4%) (P=0.85, NS). Time to recovered bowel activity and to
      resumed oral feeding were equivalent in the two groups. The mean length of
      hospital stay was longer in the delayed group (34.5 +/- 18.6 days) than in the
      early group (23.1 +/- 4.6 days) (P<0.01). CONCLUSION: Early closure of bowel
      stoma can be performed without major complications in elective patients. This
      procedure shortens hospital stay.

PMID- 14586241
TI  - [Evaluation of endoscopic diagnosis of Barrett's esophagus based on analysis of
      346 reports].
AB  - OBJECTIVES: To evaluate the different endoscopic ways of diagnosing Barrett's
      esophagus (BE) and assess the quality of BE endoscopic reports using a rating
      grid. MATERIAL AND METHODS: Three-hundred and forty-six reports concerning BE
      (1997-2000) were divided into two groups, circular and non-circular BE, and rated
      on a scale (0 to 20 points) by two readers using a grid to evaluate, in
      particular, the description of BE, hiatal hernia and esophagitis and biopsy
      practice. RESULTS: The score was >=10 points for 129 reports (37.3%). Points were
      deducted because of inadequate description of BE and hiatal hernia and
      particularly for a lack of biopsies (54% of reports). The indication of endoscopy
      (BE monitoring) and the form of medical arrangements (out- or in patients) had a
      significant effect on the mean score of the reports. Circular BE (46.5% of all
      reports) was described with respect to the height of the squamo-columnar junction
      (Z line) and the length of BE, and non-circular BE (40.4% of all reports) with
      respect to the number and height of the strips. Hiatal hernia, if detected, was
      described (67.2%) by its length, and esophagitis by standard classifications
      (70.1%). Finally, biopsy practice differed significantly as a function of the
      indication, the experience and status of the operator, or the medical management
      of the patient. CONCLUSION: This study showed that the endoscopic reports of BE
      are not sufficiently rigorous and that the absence of biopsies is frequently not
      justified. In the future, standardized reports could be proposed by working
      groups of experts and then prospectively tested and approved.

PMID- 14586242
TI  - [Hereditary nonpolyposis colorectal cancer. Definition, genetics, diagnosis, and
      medical surveillance].

PMID- 14586243
TI  - [Non-alcoholic steatosis: limits of current knowledge and lessons for
      hepatologists].

PMID- 14586244
TI  - [Virological tools for the diagnosis and follow up of hepatitis C: use and role
      of new tests].

PMID- 14586245
TI  - [Seroprevalence of hepatitis A in hospitalized patients in Limoges University
      Hospital].
AB  - AIM: Age-specific prevalence of hepatitis A virus (HAV) antibodies (IgG and IgM
      anti HAV). METHODS: For eight years between 1994 and 2002, 15 329 hospitalized
      patients were tested. RESULTS: The prevalence of anti HAV according to age group
      was as follows: 20 to 29: 28.5%; 30 to 39: 47.4%; 40 to 49: 64.8%; 50 to 59:
      82.1%; more than 90% after 60 years old and 97% in patients older than 80. This
      was not a cross sectional seroepidemiological investigation because serum samples
      were selected by prescription especially among children. Recent HAV infections as
      shown by IgM positivity (136 patients) was observed among all age groups,
      particularly before ten years old (28.7%), but was still significant after sixty
      (19.8%). CONCLUSION: The age-specific seroprevalence of HAV antibodies compared
      with previous French prevalence data revealed a good correlation with results
      obtained in West-Central region and in national investigations in general
      populations but more elevated than observed in French recruits.

PMID- 14586246
TI  - [Is chronic hepatitis C treatment as efficient in the general population as in
      randomised trials?].
AB  - AIMS: The aim of this population-based study was to determine the effectiveness
      of antiviral therapy in non selected chronic hepatitis C patients. METHODS: The
      study was performed in all new patients with anti-HCV antibodies who had
      registered in a specialised viral hepatitis registry since 1994 and who lived in
      the French departments of Cote-d'Or and Doubs (1 005 817 inhabitants). RESULTS:
      1251 of the 1508 recorded cases were studied; 262 were treated. Results of
      treatment were available in 238 cases, 157 were treated with interferon alone and
      81 with interferon + ribavirine. Sustained virological response was observed in
      18% of cases after interferon alone and 46.9% after interferon + ribavirine. In
      multivariate analysis, age under 40 and combined therapy were positively
      correlated to sustained virological response. Premature treatment discontinuation
      was associated with a lack of sustained response which was unrelated to gender or
      liver fibrosis. Fifty seven patients received combined therapy after unsuccessful
      monotherapy: sustained virological response rates were 33.3% in responders
      relapsers and 23.7% in non-responders to initial therapy. CONCLUSIONS: This study
      showed that sustained response rates were similar in non selected patients from
      the general population and in highly selected patients from randomised trials.
      These results emphasize the necessity of increasing the ratio of treated patients
      which is still too low in general population.

PMID- 14586247
TI  - [Bacterial flora and cirrhosis].

PMID- 14586250
TI  - [Non-alcoholic steatohepatitis: natural history and diagnosis].

PMID- 14586252
TI  - [A man with non alcoholic steatohepatitis].

PMID- 14586253
TI  - [Interview: questions to professor Yves Deugnier].

PMID- 14586251
TI  - [Non-alcoholic steatohepatitis: therapeutic management].

PMID- 14586256
TI  - Isolated idiopathic chronic pancreatitis associated with a compound
      heterozygosity for two mutations of the CFTR gene.
AB  - We report the case of a patient suffering from idiopathic chronic pancreatitis
      (ICP) and compound heterozygous for mutations G542X and S1235R of the cystic
      fibrosis transmembrane regulator (CFTR) gene. The patient had normal sweat test
      and no other clinical sign usually linked with a typical or moderate pathology
      (bronchiectasis, nasal polyposis, congenital absence of the vas deferens) of the
      CFTR gene. G542X is a severe mutation, which is usually found in classical cystic
      fibrosis when associated with other severe mutations. S1235R is a quite rare
      abnormality recently reported as being potentially pathogenic when combined in
      trans with a second CF mutation. Our case is quite similar to the only other six
      patients in the literature in whom only the pancreas is affected and who bear a
      rare mutation with moderate effect. The history and the clinical features of our
      patient indicate an unambiguous isolated ICP in which the presence of the S1235R
      mutation--in trans with regard to G542X--is likely responsible for the ICP
      phenotype. This case could throw light on some of the as yet poorly known
      abnormalities of the CFTR gene in the ICP phenotype.

PMID- 14586255
TI  - [Pancreatic acinar cell carcinoma in a patient with familial adenomatous
      polyposis].
AB  - The relative risk of pancreatic cancer has been shown to be about 4 times that of
      the general population in familial adenomatous polyposis patients, but its
      frequency remains low, and the histological nature of these pancreatic tumors has
      been rarely reported. We describe the case of a 65-year-old patient, with a
      history of familial adenomatous polyposis coli, who developed advanced duodenal
      polyposis and a synchronous 25 mm tumor of the pancreatic isthmus. After total
      pancreatectomy and antrectomy, histological examination revealed an acinar cell
      carcinoma and duodenal adenomas with low and high-grade dysplasia, but no cancer.
      To our knowledge, this is the first description of the association of familial
      adenomatous polyposis with acinar cell carcinoma of the pancreas.

PMID- 14586257
TI  - [Isolated ileal villous atrophy: a rare cause of chronic diarrhea. Report of a
      case and review of the literature].
AB  - Villous atrophy of the terminal ileum is usually secondary to celiac disease or
      other diseases. Very few cases of primary ileal villous atrophy have been
      reported in the literature. We report here the case of a 37-year-old man with
      chronic diarrhea since childhood without features of malabsorption. The
      macroscopic and microscopic appearance of the duodenal, ileal and colonic mucosae
      at endoscopy and contrast radiography of the small bowel was normal. Ileal
      lesions consisted of total villous atrophy. Search for antinuclear antibodies,
      anti-endomysium and anti-gliadin IgA and IgG and HIV serology were negative.
      Serum immunoglobulin level was normal. Diarrhea resolved under treatment with
      colestyramine.

PMID- 14586259
TI  - [Colonic lymphoma complicating hemorrhagic rectocolitis after liver
      transplantation].

PMID- 14586258
TI  - [Peritoneal carcinomatosis and hepatic infiltration related to the dissemination
      of a micropapillary cell carcinoma of the bladder].
AB  - Most cases of liver failure related to the infiltration of the liver by
      neoplastic cells are associated with hematological neoplasia or small cell
      carcinoma of the lung. We report case of liver failure related to a rare
      infiltration of the liver by a micropapillary bladder carcinoma. Micropapillary
      bladder cell carcinomas have recently been isolated among bladder tumors. They
      are characterized by life-threatening features as they spread rapidly to the
      interstitial stromal matrix leading to a highly aggressive course. The present
      case emphasizes the pathological features and poor prognosis of these neoplasia,
      as rapid submucosal spreading may prevent curative locoregional treatment.

PMID- 14586260
TI  - [Whipple disease revealed by weight loss and neurologic signs].

PMID- 14586261
TI  - [Primary adenocarcinoma of the cervical esophagus arising from heterotopic
      gastric mucosa].

PMID- 14586262
TI  - [Hepatic pedicle cystic mass revealing necrotic lymphatic tuberculosis].

PMID- 14586263
TI  - [Autoimmune hepatitis, acute pancreatitis, mixed connective tissue disease and
      Sjogren's syndrome. A case report].

PMID- 14586264
TI  - [Azathioprine: what's new is old].

PMID- 14586265
TI  - [Should we have the courage to say no to systematic liver biopsy?].

PMID- 14586267
TI  - The influence of glimepiride on the oxidative state of rats with streptozotocin
      induced hyperglycemia.
AB  - BACKGROUND: The aim of this work was to determine whether glimepiride, a derivate
      of sulphonylurea of the hypoglycemic effect, influences the level of prooxidative
      factors and antioxidative enzymes activity in the course of experimental
      streptozotocin hyperglycemia in rats. MATERIAL/METHODS: The studies were
      performed on healthy male Wistar rats of body weight 200+/-30 g, fed with the
      standard laboratory diet and given water ad libitum. Animals were divided into 3
      groups, each consisting of 8 rats. Group I--control animals, Group II--animals in
      which experimental hyperglycemia was induced by intraperitoneal administration of
      streptozotocin (65 mg/kg body mass), Group III--animals which were given
      glimepiride orally for seven weeks (200 mg/kg of body mass), starting 24 hours
      after streptozotocin administration. Using Ohkawa method, malondialdehyde level
      was determined in plasma for all groups. Concentration of hydrogen peroxide was
      determined using method developed by Frew and co-workers, superoxide dismutase
      activity using the Misra and Fridovich method and activity of glutathione
      peroxidase by means of Ransel kit [Randox, Great Britain]. The decrease of
      glucose level in serum of rats under the influence of streptozotocin and
      glimepiride was observed when compared with the group given placebo. RESULTS:
      Glimepiride administration caused a decrease of peroxides and malondialdehyde
      levels and increase in activity of superoxide dismutase and glutathione
      peroxidase in rats, after streptozotocin had been administered. CONCLUSIONS: The
      results suggest that glimepiride may effectively inhibit the development of the
      oxidative stress in diabetes.

PMID- 14586268
TI  - The "no-reflow" phenomenon in cerebral circulation.
AB  - BACKGROUND: The purpose of our research was to study the pattern of post-ischemic
      cerebral hemodynamic changes and observe the impact of enalapril on the course of
      these changes in cats. MATERIAL/METHODS: The experiments were carried out on
      anesthetized cats using the autohemoperfusion method in cerebral and peripheral
      vessels with a stable volume of blood. Transitional peripheral (lower limb) and
      brain ischemia was simulated by stopping the autohemoperfusion pump for 15
      minutes, tying various anastomoses in the neck region, and reducing arterial
      blood pressure (ABP) to 40-30 mm Hg, followed by reinfusion of the shed blood.
      RESULTS: Intravenous administration of enalapril solution in a dosage of 0.25 mg
      kg-1 in the early phase of reperfusion (10 minutes into the postischaemic period)
      prevented the development of long-term "no-reflow"of cerebral blood flow, as
      observed in the controls. There was a 40.8+/-3.2% reduction of cerebrovascular
      tone, 39.3+/-3.1% in peripheral vessels, and 44.7+/-1.5% lower arterial blood
      pressure at the end of 120 minutes. CONCLUSIONS: Enalapril caused a reduction of
      cerebrovascular tone, completely eliminating the "no-reflow" syndrome after brain
      ischemia and somewhat potentiated the hyperperfusion phase. At the same time, the
      drug did not aggravate the general hypotension observed after ischemia in the
      controls.

PMID- 14586269
TI  - Apoptosis in Lyme borreliosis--a preliminary study.
AB  - BACKGROUND: Apoptosis plays an important role in the control of the immune
      system, and its impairment may be associated with autoimmune responses. Different
      bacterial and viral pathogens interfere with the regulation of apoptosis. This
      may take place in Lyme borreliosis, in which pathological autoimmune reactions
      are likely to occur. MATERIAL/METHODS: A study group consisted of 15 patients
      with erythema migrans (group I), 15 with Lyme arthritis (group II) and 9 with
      neuroborreliosis (group III); the control group consisted of 10 healthy subjects.
      The concentrations of the factors involved in apoptosis regulation--transforming
      growth factor-beta1 (TGF-beta 1), soluble Fas (sFas), soluble Fas ligand (sFasL)
      and protein bcl-2--were measured in serum before (examination 1) and after
      (examination 2) four weeks of antibiotic treatment. RESULTS: The mean
      concentration of sFas was significantly higher in all study groups compared to
      controls in examination 1 and 2, and showed a tendency to increase during
      treatment. The concentration of sFasL was significantly increased in groups II
      and III in examination 1. The concentration of bcl-2 was elevated significantly
      in all groups in examination 1 and dropped during treatment, remaining
      significantly increased in group I. The concentration of TGF-beta 1 was not
      significantly elevated except for group II in examination 2. CONCLUSIONS: The
      concentrations of soluble factors involved in the regulation of apoptosis were
      increased in serum of patients with different forms of Lyme borreliosis. Further
      studies are necessary to confirm if inappropriate apoptosis of immune cells may
      contribute to the pathogenesis of Lyme disease.

PMID- 14586270
TI  - Ventricular long axis function is predictive of outcome in patients with chronic
      heart failure secondary to non-ischemic dilated cardiomyopathy.
AB  - BACKGROUND: Ventricular long axis function has recently been proved to be of
      prognostic value in patients with heart failure. However, it remains unclear
      whether it can provide additional independent information over that provided by
      conventionally used LVEF or functional status. We conducted this study to address
      this issue, and to determine the prognostic importance of sequential change in
      long axis function over time in patients with idiopathic DCM. MATERIAL/METHODS:
      We prospectively followed up 299 DCM patients with mean age of 55.5 years and
      LVEF of 41%. All patients underwent a complete clinical and echocardiographic
      evaluation including ventricular long axis function at baseline, 1- and 2-year
      follow-up. RESULTS: At the end of study, 50 patients died and 6 underwent cardiac
      transplantation. The majority of deaths occurred before the second examination.
      In univariate analysis, the absolute values of RV and LV long axis functions at
      the second examination were significantly related to mortality. In multivariate
      regression model, they did not maintain their prognostic values. However, a
      sequential increase in the LV long axis function significantly predicted
      prognosis, independently of age, NYHA class, and exercise tolerance. The
      subsequent survival of patients with increased LV long axis function was
      significantly better than those with either a decrease or no change in it.
      CONCLUSIONS: This study clearly indicates that the sequential increase of long
      axis function was related to significantly better survival in idiopathic DCM
      patients, which provides a novel method to estimate prognosis of these patients
      with moderate impairment of LVEF at initial presentation.

PMID- 14586271
TI  - Educational attainment and risk of stroke and myocardial infarction.
AB  - BACKGROUND: Prior reports have suggested that low educational attainment could be
      associated with higher incidence of some of the cardiovascular conditions.
      MATERIAL/METHODS: We evaluated the association of educational attainment (> or
      =12 years or <12 years) with the incidence of fatal strokes, ischemic stroke,
      intracerebral hemorrhage, and myocardial infarction in a cohort of 21,443 United
      States adults who participated in either the First National Health and Nutrition
      Examination Survey (NHANES-I) Epidemiologic Follow-up Study (NHEFS) or the Second
      National Health and Nutrition Examination Survey Mortality Follow-up Study
      (NHANES-II). Cox proportional hazards analyses were used to examine the
      relationships. RESULTS: During a mean follow-up period of 15.2+/-4.6 years, the
      risk for all fatal strokes was increased in persons who reported less than 12
      years of education. The increased risk was more prominent in persons aged 50
      years or less (relative risk [RR], 2.6; 95% confidence interval [CI], 1.1-6.0)
      compared with persons aged greater than 50 years (RR, 1.3, 95% CI, 1.0-1.6). A
      higher risk of myocardial infarction associated with less than 12 years of
      education was observed in both persons aged 50 years or less (RR 1.7, 95% CI 1.2
      2.4) and those aged greater than 50 years (RR 1.3, 95% CI 1.1-1.5). The risk for
      fatal intracerebral hemorrhages (RR 2.0, 95% CI 1.1-3.5) was higher in persons
      with less than 12 years of education (no significant interaction demonstrated
      with age). CONCLUSIONS: Educational attainment has a significant effect on the
      risk for stroke and myocardial infarction, independent of socioeconomic status
      and other cardiovascular risk factors.

PMID- 14586272
TI  - Do we need all three criteria for the diagnostic separation of pleural fluid into
      transudates and exudates? An appraisal of the traditional criteria.
AB  - BACKGROUND: Classification of pleural effusions into transudates and exudates is
      based on pleural fluid absolute lactic dehydrogenase value (FLDH), fluid to serum
      ratio of LDH (LDHR) and fluid to serum ratio of total protein (TPR) used in a
      parallel combination strategy. Combining multiple tests in a parallel strategy to
      improve diagnostic accuracy is useful only if the pair-wise correlation of the
      individual tests is less than 0.75. So far, this concept has not been tested in
      patients with pleural effusions. MATERIAL/METHODS: Biochemical data from our 200
      patient series with a known cause of pleural effusion were included in this
      study. Correlation between the three possible combinations of tests was
      determined. RESULTS: There were 116 males and 84 females. The mean age was 62+/
      1.1 years (mean+/-SEM). Of the 200 effusions, 156 were exudates and 44 were
      transudates. There was a significant correlation between FLDH and LDHR (r=0.93,
      p<0.00). However, the correlation between FLDH and TPR (r=0.27) and TPR and LDHR
      (r=0.22) was not significant. CONCLUSIONS: The operative mechanism for LDHR and
      FLDH used in the classification of transudate and exudates appears to be similar,
      and therefore unsuitable for a parallel combination strategy in the diagnostic
      separation of pleural effusion. FLDH and TPR have a dissimilar operating
      mechanism, and can therefore be combined in this process. Therefore, the
      diagnostic separation of pleural effusion can be done cost effectively by
      utilizing FLDH and TPR alone, as the cost for estimating serum LDH is eliminated
      in this approach.

PMID- 14586273
TI  - The use of corticosteroids versus other treatments for Graves' ophthalmopathy: a
      quantitative evaluation.
AB  - BACKGROUND: The purpose of the present study was to evaluate the efficacy of
      corticosteroids in the treatment of Graves' ophthalmopathy in comparison to other
      treatment modalities. MATERIAL/METHODS: 15 studies were identified but only 14
      were included in the final analysis, 5 cohort and 9 randomized. A total of 813
      patients were included in this quantitative review. RESULTS: The relative risk
      with oral corticosteroid treatment (OCS) alone vs. other treatment could not be
      pooled, as the studies were heterogeneous and the RR was dependent on risk of
      failure in the control group. In the two studies that reported head-on comparison
      between OCS and radiotherapy, no clinically significant difference was found.
      However, the combination of OCS and radiotherapy was markedly more effective than
      either modality alone (pooled RRR 70%). The number of patients who should be
      treated with the combination of CS and radiotherapy to prevent one more failure
      was between 3 to 8. Evidence from the studies suggest that intravenous
      corticosteroid's IVCSs used alone have similar or greater efficacy than the
      combination. CONCLUSIONS: Corticosteroids seem to be an effective treatment for
      Graves' ophthalmopathy compared to other treatments currently available. Oral
      corticosteroids appear to have increased effect when given with radiotherapy.
      IVCSs, with or without radiotherapy, seem to have the best documented efficacy.
      Side effects can also be overcome by the use of IVCS pulse therapy (without OCS),
      which needs to be pursued in further, separate research as an alternative to oral
      therapy, since it could be both more effective and safer.

PMID- 14586274
TI  - Total tau in cerebrospinal fluid differentiates Alzheimer's disease from vascular
      dementia.
AB  - BACKGROUND: Tau protein is a microtubule-associated protein located in neuronal
      axons, which has been used in various configurations as a diagnostic marker of
      degenerative changes in the CNS. The aim of our study was to evaluate the use of
      CSF/ total tau in patients with Alzheimer-type dementia (AD) and vascular
      dementia (VD) compared to controls, in order to investigate. MATERIAL/METHODS: A
      total of 102 persons were included in the study: 58 AD patients, 24 VD patients,
      and 20 non-demented controls. The Alzheimer group was divided into 3 subgroups by
      clinical stage of the disease. CSF samples were collected by routine lumbar
      puncture. The level of total tau protein was determined by sensitive sandwich
      enzyme-linked immunosorbent assay (ELISA). RESULTS: CSF/total tau in the AD group
      was significantly higher than in the VD group (median 385.6 pg/ml vs. 101.2
      pg/ml) and the controls (1.37 pg/ml). There were also significant differences
      among the AD stage groups in CSF total tau: highest in the group with severe
      dementia, intermediate in the group with moderate dementia, and lowest in the
      group with mild dementia. Differences in CSF total tau in all groups are not
      attributable to the patients' age. CONCLUSIONS: CSF total tau clearly and simply
      differentiates AD from VD. CSF total tau in the incipient stage of AD and its
      increase in parallel with the progression of the disease may also provide a
      biochemical test to monitor the development of the disease.

PMID- 14586275
TI  - Evidence against the fecal-oral route of transmission for Helicobacter pylori
      infection in childhood.
AB  - BACKGROUND: Acquisition of Helicobacter pylori (H. pylori) occurs mainly in
      childhood. However, little is known about the mode of transmission. In such
      developing countries as Turkey, where the hygienic situation facilitates the
      transmission of hepatitis A virus (HAV), infection with HAV is mainly transmitted
      via the enteral route. Therefore, it seemed advisable to evaluate the role of
      fecal-oral transmission in the spread of H. pylori. MATERIAL/METHODS: Blood
      samples taken from healthy children (n= 90) 2-16 years old were studied for anti
      H. pylori and anti-hepatitis A antibodies by enzyme immunoassay. RESULTS: Of the
      90 children, 33.3% were seropositive for both H. pylori and HAV, 33.3% were
      seronegative for both, 8.9 % were seropositive for H. pylori only, and 24.4% were
      seropositive for HAV only. The percentage of seropositive children increased with
      age for H. pylori and HAV. There was no significant relationship in
      seroprevalence between H. pylori and HAV when analyzed by logistic regression
      analysis (p=0.178). CONCLUSIONS: This study suggests that the seropositivity
      rates of H. pylori and HAV increase with age, while the fecal-oral route may not
      be an important mode of transmission for H. pylori in children living in western
      Anatolia, in the Manisa region.

PMID- 14586276
TI  - Lost to follow-up: the bottleneck of early referral to renal units?
AB  - BACKGROUND: Early referral is a major goal in chronic kidney diseases; however,
      loss to follow-up, potentially limiting its advantages, has never been studied.
      MATERIAL/METHODS: In order to assess the prevalence and causes of loss to follow
      up, a telephone inquiry was performed in a renal outpatient unit, mainly
      dedicated to early referral of diabetic patients. Patients were considered to be
      in follow-up if there was at least one check-up in the period February 2001
      February 2002, and lost to follow-up if the last check-up had occurred in the
      previous year. The reasons for loss to follow-up were related to typical clinical
      biochemical parameters to define a "drop-out profile". RESULTS: 195 patients were
      on follow-up: median creatinine 1.4 mg/dL, age 64, 76.9% diabetics. 81 patients
      were lost to follow-up: creatinine 1.4 mg/dL, age 70, 73.8% diabetics. A
      telephone number was available in 87.6% of the cases; 25 were not found, 7 had
      died, 24 were non-compliant, 1 was bed-ridden, 12 had changed care unit, 2 had
      started dialysis. Renal care was shorter in those lost to follow-up; among the
      latter, serum creatinine and age were significantly lower in non-compliant
      patients. A logistic regression model confirmed the significance of lower serum
      creatinine at last check-up in non-compliant patients (p=0.018). CONCLUSIONS:
      Loss to follow-up is a problem in nephrology; lack of awareness probably causes
      the higher drop-out rate at lower creatinine levels. The initial period of care
      may be crucial for long-term compliance. Further studies are needed to tailor
      organizational and educational interventions.

PMID- 14586277
TI  - Dialysis adequacy, residual renal function and serum concentrations of selected
      low molecular weight proteins in patients undergoing continuous ambulatory
      peritoneal dialysis.
AB  - BACKGROUND: Low molecular weight proteins (LMWP) are considered uremic toxins.
      There is controversy whether in peritoneal dialysis (PD) the elimination of these
      toxins is influenced mainly by dialysis or by residual renal function (RRF).
      MATERIAL/METHODS: The aim of our study was to evaluate the relationship between
      serum levels of selected LMWPs, dialysis adequacy, and RRF in PD patients. 27
      stable subjects were studied, mean age 50+/-11, dialyzed for a median period of
      10 months. Serum activity of acid RNA-se and alkaline RNA-se was measured by
      spectrophotometry, and serum alpha1-microglobulin ((alpha) 1M) concentration by
      ELISA. Kt/V and weekly creatinine clearance (wClCr) were assessed as adequacy
      indices (both as the sum of renal and dialysis components) and RRF as the mean of
      residual urea and creatinine clearances. RESULTS: Significant inverse
      correlations were found between RRF and (alpha) 1M level, as well as alkaline RNA
      se activity (p<0.0001). A similar relationship was found for residual Kt/V
      (p<0.0001 for (alpha) 1M and alkaline RNA-se). There was no significant
      correlation between acid RNA-se activity and any tested parameter of adequacy.
      When the cutoff points of wClCr = 60 L/week/m2, total Kt/V = 2.0, or RRF=2.0
      ml/min were used, we found (alpha)1M level and alkaline RNA-se activity to be
      significantly lower in patients with higher values of the CONCLUSIONS: RRF plays
      an important role in elimination of LMWP in PD. The activity of alkaline RNA-se
      and acid RNA-se behaves differently in these patients.

PMID- 14586278
TI  - Case of sublingual hematoma threatening airway obstruction.
AB  - BACKGROUND: The complications of warfarin therapy have classically been described
      as bleeding in the genitourinary and gastrointestinal tracts, skin, central
      nervous system, nose, penis, or retroperitoneum. However, rarely warfarin may
      cause bleeding that compromises a patient's airway. A sublingual haematoma is an
      example of such a complication. Only 10 previous cases of sublingual haematomas
      have been reported. CASE REPORT: We describe the case of a 56 year-old woman
      receiving oral anticoagulation who presented with a sore throat and hoarseness.
      Examination of her oral cavity revealed a soft, red, submucosal swelling
      involving the floor of mouth and ventral lingual surface bilaterally. No signs of
      airway compromise were observed. The patient's PT-INR was 10. Given the potential
      for rapid airway obstruction, the patient was admitted to a unit with closely
      monitored beds. Her coagulation disturbance was corrected medically and her
      haematoma resolved. The patient was discharged to the care of her family
      physician. CONCLUSIONS: This case makes several important points. First, the case
      describes a rare, but life-threatening complication of warfarin therapy. Second,
      the initial signs of a sublingual haematoma are reviewed. Given the vagueness of
      these signs, diagnosis requires a high index of suspicion on the part of the
      physician. Finally, the case describes successfully management of this disorder
      without the use of a surgical airway. For this patient, reversal of her
      anticoagulation and vigilant monitoring saved her from having a surgical airway
      placed.

PMID- 14586279
TI  - Esophageal leiomyomatosis.
AB  - BACKGROUND: Esophageal leiomyomatosis is rare with an incidence that is
      essentially unknown with only a few reported cases. Characteristically there is
      proliferation of smooth muscle cells in the esophageal wall causing localized
      circumferential thickening. Esophageal leiomyomas are usually very slow growing
      and often asymptomatic. Symptomatic tumors are usually greater than five
      centimeters in diameter. The accepted treatment for esophageal leiomyomatosis has
      been surgical removal, which frequently requires esophagectomy with
      reconstruction. CASE REPORT: We report a case of a 29-year-old woman with
      esophageal leiomyomatosis whose presentation was not typical and magnetic
      resonance imaging proved diagnostic. This patient was effectively with
      enucleation of the tumor. CONCLUSIONS: Recommended treatment for this condition
      has been total esophagectomy with reconstruction, but we report a case treated
      with enucleation of the tumor.

PMID- 14586280
TI  - Methylene blue: an effective treatment for contrast medium-induced anaphylaxis.
AB  - BACKGROUND: The purpose of this paper is to propose methylene blue as a
      lifesaving alternative drug for the treatment of contrast-induced anaphylaxis.
      CASE REPORT: In a cardiovascular catheterization laboratory invasive hemodynamic
      monitoring was used to document the lifesaving effect of IV bolus injections of
      1.5-2 mg/Kg methylene blue solution to treat three patients for anaphylactic
      shock following radiocontrast injection during coronary angiography. Methylene
      blue administration was followed by prompt circulatory improvement, leading to
      hemodynamic stabilization and relief of other anaphylactic symptoms in each case.
      There were no deaths. CONCLUSIONS: Our findings suggest that methylene blue can
      be lifesaving in anaphylactic shock, notwithstanding some transitory side
      effects, such as cardiac rhythm disturbances and chest pain, both of which
      possibly originate from sudden myocardial perfusion deficits.

PMID- 14586281
TI  - Radiofrequency heat ablation for lung tumors: potential applications.
AB  - Radiofrequency ablation (RFA) is an image guided percutaneous procedure using
      thermal energy that is used to treat malignant lesions in various organs
      including liver, breast and lungs. It has also been used bronchoscopically to
      treat endobronchial tumors. Current passing through tissue from the active
      electrode leads to ion agitation, which is converted by means of friction into
      heat leading to irreparable cellular damage and coagulation necrosis. The
      potential benefits include decreased cost and morbidity, treating patients who
      are not surgical candidates due to age, co-morbidity or extent of disease and the
      possibility of performing the procedure on an outpatient basis. The aim is
      usually to reduce tumor size. Whether it can be used with a curative intent in
      well localized primary tumors remains to be determined by well designed studies.
      However, caution should be exercised because selective tumor resection is not the
      gold standard to treat potentially resectable lung malignancies that are treated
      with lobectomy. Obviously, lung volume reduction surgery combined with tumor
      resection has challenged this approach. RFA might be the treatment of choice for
      multiple lung metastases that are usually approached surgically for long-term
      remission. A specific indication may also be bilateral pulmonary metastases.
      Other potential applications might be tumor size reduction by a non-surgical
      procedure followed by adjuvant chemotherapy. Currently, these thoughts remain
      only speculations, until proven by clinical trials with medium to long-term
      follow up. Furthermore, the risk of this procedure for pulmonary application has
      to be better defined.

PMID- 14586282
TI  - Eye birth defects in humans may be caused by a recessively-inherited genetic
      predisposition to the effects of maternal vitamin A deficiency during pregnancy.
AB  - Congenital malformations of the eye can cause blindness in children. They occur
      throughout the world and in most cases the aetiology is unknown. Linkage studies
      have largely been unsuccessful and the risk to siblings is generally low.
      Epidemiological and laboratory evidence support a hypothesis that there may be
      genetic (recessive) predisposition to the teratogenetic effects of mild to
      moderate maternal vitamin A deficiency (VAD) during pregnancy. This may explain
      the higher prevalence of congenital eye anomalies in a part of Asian countries,
      where maternal VAD is common and consanguineous marriages are popular. Other
      congenital malformations commonly found in association with ocular coloboma (e.g.
      oesophageal fistulae and heart defects in CHARGE association) may also be VAD
      related. Mutations in a gene involved in the cellular access to vitamin A that
      normally protects the tissue or embryo from natural variation in dietary vitamin
      A intake, could render that individual intolerant of conditions of VAD. An
      interaction of this kind could also explain a proportion of "sporadic" cases in
      locations where VAD is uncommon. If this interaction is shown to be true, there
      are public health implications for the prevention of blindness due to congenital
      eye malformations. The hypotheses proposed above are reminiscent of the research
      leading to the discovery that folic acid supplementation could prevent neural
      tube defects. However, this form of intervention would be much more difficult
      with vitamin A, which is itself a powerful teratogen if present in excess.

PMID- 14586283
TI  - From railway spine to whiplash--the recycling of nervous irritation.
AB  - The search for a specific structural basis for chronic whiplash and other chronic
      pain and fatigue syndromes has been in progress for decades, and yet currently
      there remains no "structural" solution to these enigmata. In light of the failure
      of research to identify the chronic "damage" or pathology as lying in a muscular,
      bony, or "connective tissue" sites for many chronic pain syndromes like whiplash,
      fibromyalgia, et cetera, more recent attention has been paid to nervous system
      structures. Nerve irritation has been implicated as the basis for the pain and
      other symptoms that are common to many chronic disability syndromes. We postulate
      here, however, that the concept of nervous irritation has been prostituted for
      centuries whenever more concrete structural explanations for chronic pain and
      other controversial illness have been untenable. We suggest that, after each
      cycle of nervous irritation as a disease, and subsequent dismissal of the notion,
      the doctrine of irritation as a disease was too good to go away. First, with the
      hypersthenic and asthenic diseases of the nineteenth century, then railway spine,
      whiplash, thoracic outlet syndrome, and now brachial plexus irritation, we detect
      the same pattern: patients with symptoms, but no objective evidence of nerve
      disease. Nervous irritation has repeatedly served this purpose for the last 200
      years. It is our intent that bringing an understanding of this trend will
      encourage current clinicians and researchers to appreciate the need to abandon
      this form of speculation without historical insight when dealing with today's
      controversial syndromes.

PMID- 14586284
TI  - Survivin--an anti-apoptosis protein.

PMID- 14586285
TI  - Adiponectin and HIV associated lipodystrophy.

PMID- 14586286
TI  - Abnormal amniotic fluid volume as a screening test prior to targeted ultrasound.
AB  - BACKGROUND: The purpose of this study was to examine (1) the association between
      amniotic fluid volume (AFV) and sonographically detected fetal structural
      anomalies, and (2) the effectiveness of using abnormal AFV as a screening test
      prior to patient referral for a targeted ultrasound. MATERIAL/METHODS: For
      singleton pregnancies in the 2nd and 3rd trimester frequencies of individual
      anomalies and odds ratios were calculated for each category of amniotic fluid
      volume relative to the frequency of anomalies with normal volume. The anomaly
      detection rate and frequency of referral for targeted ultrasound on the basis of
      abnormal amniotic fluid volume were calculated. RESULTS: 15,959 (92.0%) of
      patients had normal amniotic fluid volume, 537 (3.1%) decreased, 544 (3.1%)
      increased, 167 (1.0%) oligohydramnios, and 141 (0.8%) polyhydramnios. There were
      365 (2.1%) fetuses with major structural anomalies. 1.8% of patients with normal
      AFV had anomalies. Anomalies were significantly more frequent in all categories
      of abnormal fluid: decreased (3.2%, OR 1.74, 95% CI 1.06-2.86), increased (5.7%,
      OR 3.22, 95% CI 2.2-4.71), oligohydramnios (9.0%, OR 5.26, 95% CI 3.09-9.05), and
      polyhydramnios (5.7%, OR 3.21, 95% CI 1.56-6.6). Referral for targeted ultrasound
      based on any abnormal AFV volume compared to only oligohydramnios or
      polyhydramnios increased the overall anomaly detection rate by nearly three-fold
      (19.5% vs. 6.3%), with minimal changes in the number of referrals per anomaly
      detected (13.4 vs. CONCLUSIONS: Referral for targeted ultrasound in the presence
      of even minor abnormalities of amniotic fluid would significantly improve anomaly
      detection with minimal increase in referrals.

PMID- 14586288
TI  - CT-guided radiofrequency heat ablation of malignant lung tumors.
AB  - BACKGROUND: Radiofrequency heat ablation (RFA) is an advanced minimal-invasive
      technique for the treatment of primary and secondary malignancies in several
      organs. This article presents the successful percutaneous computed tomography
      (CT)-guided radiofrequency heat ablation of a peripheral bronchiogenic carcinoma
      and four lung metastases in three patients. MATERIAL/METHODS: Pain relief in a
      palliative care situation was the indication for RFA treatment in two patients. A
      primary curative tumor treatment with RFA was intended in one patient, who
      refused surgery. All procedures were performed under conscious sedation and local
      anesthesia. RESULTS: RFA treatment was carried out without major complications in
      these patients. No signs of infection or significant bleeding were observed. One
      patient developed a pneumothorax two days after the procedure, which was drained
      sufficiently. All patients had elevated temperatures, up to 38.5 degrees C for
      three days after RFA, due to tumor lysis. Pain relief was possible. Control CT
      scans three months after percutaneous RFA revealed shrinkage of the treated tumor
      nodules. CONCLUSIONS: Percutaneous RFA was successfully performed in three
      patients. CT-guided percutaneous RFA of non-resectable lung neoplasms may be a
      complement to chemotherapy and radiation therapy. Further clinical experience and
      prospective studies are needed to determine the long-term efficacy and safety of
      RFA in the treatment of lung tumors.

PMID- 14586287
TI  - Rapid diagnosis of tuberculous meningitis using the Simple Dot ELISA method.
AB  - BACKGROUND: Tuberculous meningitis (TBM) is a serious central nervous system
      infection, which is seen in clinical practice fairly frequently in developing and
      underdeveloped countries. Our study was intended to develop a reliable and rapid
      diagnostic methodology for detecting mycobacterium tuberculous bacilli (MTB) in
      cerebrospinal fluid (CSF). Dot Enzyme Linked Immunosorbent assay (Dot ELISA) has
      been standardized to detect MTB antigens and antibodies against MTB in the CSF of
      TBM patients. MATERIAL/METHODS: CSF samples were collected from 156 registered
      patients suffering from various neurological disorders, including 56 cases of
      TBM. Polyclonal antibodies to Culture Filtrate Protein (CFP), H37Rv strain, an
      MTB antigen, obtained from Colorado State University (USA), were used to detect
      MTB antigen in the CSF of TBM patients using the Dot ELISA method. RESULTS: The
      methodology yielded a positive reaction to MTB antigens in 48 CSF samples (86%)
      obtained from all 56 cases of suspected TBM. The sensitivity achieved through the
      developed methodology could give reactivity with an antigen level 10ng/dl and
      above. Dot ELISA for MTB antigen was positive in only 5 out of 100 (5%) of the
      other neurological disorders, mainly pyogenic meningitis. CONCLUSIONS: This rapid
      methodology for the detection of MTB antigen in CSF is very simple, sensitive,
      specific, and cost effective. This technique can be easily and routinely employed
      in the pathology laboratory to support the clinical diagnosis.

PMID- 14586289
TI  - Cytostatic and cytotoxic effects of alkylglycerols (Ecomer).
AB  - BACKGROUND: Shark liver oil, with a standardized concentration of alkylglycerols
      and their methoxyderivates, has been widely used in Scandinavian countries as
      complementary medicine in the treatment of different forms of cancer. The aim of
      our study was to verify the hypothesized antiproliferative effect of
      alkylglycerols in different human cancer cell lines. MATERIAL/METHODS: The
      plating efficiency method was used to assay the effect of alkylglycerols on the
      plating efficiency of human ovarian carcinoma (OVP-10), mammary carcinoma (MCF
      7), and prostate cancer (DU-145, PC-3 and PCa-2b) cell lines. Tumor colonies
      containing more than 20 cells were scored as positive. Flow cytometry was applied
      to identify necrotic vs. apoptotic mode of cell death. The cells were exposed to
      Ecomer shark liver oil containing 20% alkylglycerols and 3% methoxyderivates in a
      dose of 0.1 mg/ml, up to a concentration corresponding to LD-50. Apoptotic and
      necrotic cells were stained with Anexin V and propidium iodine respectively.
      RESULTS: The prostate cells from DU-145, PC-3 and PCa-2B showed a dramatic
      reduction in the colony number even after relatively small doses of 0.5 and 0.1
      mg/ml medium. Flow cytomery showed an increased percentage of apoptotic cells of
      ovarian and prostate carcinoma, while mammary carcinoma cells showed
      predominantly necrotic cells after exposure to Ecomer. CONCLUSIONS: The
      alkylglycerols and their methoxyderivates present in Ecomer shark liver oil
      showed a clear apoptotic/necrotic effect on human prostate and mammary carcinoma
      cell lines.

PMID- 14586290
TI  - Macrolide therapy of chronic Lyme Disease.
AB  - BACKGROUND: Macrolide antibiotics are highly active in vitro against
      B.burgdorferi, but have limited efficacy in the treatment of patients with Lyme
      Disease. As macrolides are less active at a low pH, their poor clinical activity
      might be due to localization of borrelia to an acidic endosome, and their
      activity improved by alkalinization of that compartment with hydroxychloroquine.
      MATERIAL/METHODS: 235 patients with a multi-symptom complex typical of chronic
      Lyme disease, ie fatigue, musculoskeletal pain, and neurocognitive dysfunction
      and with serologic reactivity against B.burgdorferi were treated with a macrolide
      antibiotic (eg clarithromycin) and hydroxychloroquine. RESULTS: Eighty % of
      patients had self-reported improvement of 50% or more at the end of 3 months.
      After 2 months of treatment, 20% of patients felt markedly improved (75-100% of
      normal); after 3 months of treatment, 45% were markedly improved. Improvement
      frequently did not begin until after several weeks of therapy. There were no
      differences among the three macrolide antibiotics used. Patients who had been on
      hydroxychloroquine or macrolide antibiotic alone had experienced little or no
      improvement. Compared to patients ill for less than 3 years, the onset of
      improvement was slower, and the failure rate higher in patients who were ill for
      longer time periods. CONCLUSIONS: These results support the hypothesis that the
      Lyme borrelia reside in an acidic endosome and that the use of a lysosomotropic
      agent augments the clinical activity of macrolide antibiotics in the treatment of
      patients with chronic Lyme Disease. In contrast, the efficacy of tetracycline in
      such patients is not affected by hydroxychloroquine.

PMID- 14586291
TI  - Mitogenic lectins.
AB  - Lectins have captured the attention of a large number of researchers on account
      of the various exploitable activities that they exhibit, including their
      proliferative effects on various cell types. Recognition of cell-surface
      carbohydrates by lectins has broad implications in important biological
      processes. The ability of lectins to detect subtle variations in carbohydrate
      structures on the surface of cells and tissues has made them a paradigm for
      protein-carbohydrate recognition. Lectins display a considerable repertoire of
      carbohydrate specificities. These characteristics, together with the ability to
      stimulate lymphocytes as well as other cells, have made lectins an important
      diagnostic and experimental tool to study the various aspects of cell growth and
      differentiation, taking lymphocytes as the cell type. Various models of lectin
      action have been used to explain specific event-driven functions of lectins,
      which have convincingly elucidated the mechanism of action of lectins in
      different milieu. This review contains a selective survey of information
      available on the role of lectins in cell proliferation, with special emphasis on
      lymphocyte proliferation and the models which have been proposed to elucidate
      lectin action. The information available clearly justifies the observation that a
      generalized scheme to explain the diverse roles played by lectins in cell growth
      and differentiation is still awaited.

PMID- 14586292
TI  - The role of neurosteroids in the anxiolytic,antidepressive- and anticonvulsive
      effects of selective serotonin reuptake inhibitors.
AB  - The introduction of SSRIs to the clinic was a turning point in the treatment of
      depression and related mental disorders. Nowadays, it is becoming more and more
      evident that SSRIs are equally effective in anxiety states and some types of
      epilepsy. However, the mechanism of their central action is not fully understood.
      They not only block the serotonin transporter, but also bind to different types
      of monoaminergic receptors (serotonergic, dopaminergic) and interact with the
      synthesis of neurosteroids, in this way modifying the excitability of the central
      nervous system. The aim of this review is to update information on the
      preclinical and clinical effects of SSRI, with special emphasis put on the
      probable role of neurosteroids and the GABAA receptor complex in the mechanism of
      their action.

PMID- 14586295
TI  - Efficiency of quarantine during an epidemic of severe acute respiratory syndrome-
      Beijing, China, 2003.
AB  - During March--July 2003, an epidemic of severe acute respiratory syndrome (SARS)
      in Beijing, China, accounted for 2,521 probable cases (attack rate: 19 per
      100,000 population). To control the epidemic, public health officials initiated
      enhanced surveillance, isolation of SARS patients, use of personal protective
      equipment (PPE) by health-care workers, and quarantine of contacts of known SARS
      patients. Approximately 30,000 Beijing residents were quarantined in their homes
      or quarantine sites. To guide future quarantine policy, the Chinese Field
      Epidemiology Training Program (China FETP) of the Chinese Center for Disease
      Control and Prevention (China CDC) conducted a survey to estimate the risk for
      acquiring SARS among quarantined residents of Haidian District (2001 population:
      2.24 million), Beijing, in May 2003, 1 month after the epidemic peaked. This
      report summarizes the results of that survey, which indicate that, as a component
      of a comprehensive SARS-control program, quarantine should be limited to persons
      who have contact with an actively ill SARS patient in the home or hospital,
      allowing for better focus of resources in future outbreaks.

PMID- 14586293
TI  - Anthrax--an overview.
AB  - Anthrax, a disease of mammals (including humans), is caused by a spore-forming
      Gram-positive bacilli called Bacillus anthracis. Anthrax is one of the oldest
      threats to humanity, and remains endemic in animals in many parts of the world.
      The incidence of anthrax has decreased in developed countries, but it remains a
      considerable health problem in developing countries. The disease is transmitted
      to humans by contact with sick animals or their products, such as wool, skin,
      meat etc. Capsular polypeptide and anthrax toxin are the principal virulence
      factors of B. anthracis. Anthrax toxin consists of three proteins called
      protective antigen, edema factor, and lethal factor, each of which is nontoxic
      but acts synergistically. Human anthrax has three major clinical forms:
      cutaneous, inhalational, and gastrointestinal. The diagnosis is easily
      established in cutaneous cases, characterized by black eschar. Severe
      intoxication and collapse during the course of bronchopneumonia or hemorrhagic
      enteritis should prompt suspicion of anthrax. Treatment with antibiotics is
      mandatory. If untreated, anthrax in all forms can lead to septicemia and death.
      Recently, considerable attention has been focused on the potential for B.
      anthracis to be used in acts of biological terrorism. The ease of laboratory
      production and its dissemination via aerosol led to its adoption by terrorists,
      as shown by recent events in the USA. A good knowledge of anthrax, its
      epidemiology, pathogenesis, clinical forms and potential as a biological weapon
      is essential for timely prevention and treatment. This review summarizes the
      current knowledge on anthrax.

PMID- 14586296
TI  - Prevalence of selected risk factors for chronic disease--Jordan, 2002.
AB  - In Jordan, the average life expectancy in 2002 was 72 years, and chronic diseases
      are becoming increasingly prevalent. Because personal behavior can influence the
      occurrence and progression of many chronic diseases, the Jordan Ministry of
      Health (JMoH) established surveillance for behavioral risk factors, particularly
      those related to cardiovascular diseases and diabetes. This report summarizes the
      key findings of the 2002 Behavioral Risk Factor Survey, the first reporting
      segment in Jordan's surveillance program for chronic diseases. The findings
      indicate that smoking, physical inactivity, and obesity contribute substantially
      to the burden of chronic disease in Jordan and underscores the need for effective
      public health interventions.

PMID- 14586297
TI  - Measles epidemic attributed to inadequate vaccination coverage--Campania, Italy,
      2002.
AB  - In Italy, measles has been a mandatory reportable disease for >100 years. During
      the prevaccination era, approximately 25,000-90,000 cases were reported annually.
      During the late 1980s and 1990s, incidence declined with increasing measles
      vaccination coverage, but measles epidemics continued to occur periodically, most
      recently during 1995-1997. In early 2002, measles incidence increased sharply;
      the area most affected was Campania (2001 population: approximately 5,782,000,
      including 1,100,000 children aged <15 years), a large region in southern Italy.
      In 2001, estimated measles vaccination coverage for the 1998 Campania birth
      cohort was 65%. Regional health authorities and the National Institute of Health
      investigated the measles outbreak in Campania. This report summarizes the
      preliminary results of the investigation, which attributed the epidemic to
      inadequate vaccination coverage. A coordinated effort is needed to interrupt
      measles transmission in Italy.

PMID- 14586298
TI  - Barium toxicity after exposure to contaminated contrast solution--Goias State,
      Brazil, 2003.
AB  - Barium-containing contrast solutions are commonly used in radiologic studies. On
      May 22, 2003, three patients at radiology clinics in Goias State, Brazil, were
      hospitalized after ingesting such solutions; two persons died within 24 hours of
      hospitalization. Exposure occurred during radiologic examination of the upper or
      lower gastrointestinal tract. An investigation was conducted by municipal and
      state public health authorities with assistance from the Ministry of Health's
      National Agency for Sanitary Surveillance (ANVISA) and Brazil's Field
      Epidemiology Training Program (FETP), known locally as EPISUS. This report
      summarizes the results of that investigation, which found that 44 persons had
      suspected barium toxicity, nine of whom died. Eight of the nine deaths were
      linked to a single lot of brand A contrast solution. A national recall was
      announced on May 23, and the manufacturing facility was inspected and closed.
      Clinicians should be alert for signs of barium toxicity in patients in the hours
      after administration of contrast solutions during radiologic studies.

PMID- 14586299
TI  - Assessment of the epidemiologic capacity in state and territorial health
      departments--United States, 2001.
AB  - Epidemiology is essential for the detection, control, and prevention of major
      health problems. Described as the foundation of all public health functions,
      epidemiology provides information needed to perform the 10 essential public
      health services. One of the national health objectives for 2010 calls for
      increases in the proportion of tribal, state, and local public health agencies
      that provide or ensure comprehensive epidemiology services to support essential
      public health services (objective 23-14). Although national infectious disease
      capacity has been assessed, no comprehensive national assessment of epidemiologic
      capacity has been conducted. To assess core epidemiology and infectious disease
      capacity of public health departments, the Council of State and Territorial
      Epidemiologists (CSTE) surveyed state and territorial health departments in
      November 2001, immediately before the release of approximately 1 billion dollars
      in federal funding to state health departments for terrorism and public health
      emergency preparedness. This report summarizes the results of that survey, which
      indicate that the national epidemiology infrastructure in state and local health
      departments is far below optimal capacity and that approximately 42% of
      epidemiologists working in public health have no formal epidemiologic training.
      Although recent terrorism preparedness initiatives have improved capacity in
      infectious disease epidemiology, increased resources are needed to build
      epidemiologic capacity necessary to address the major causes of morbidity and
      mortality.

PMID- 14586300
TI  - Terrorism preparedness in state health departments--United States, 2001-2003.
AB  - The anthrax attacks in fall 2001 highlighted the role of infectious disease (ID)
      epidemiologists in terrorism preparedness and response. Beginning in 2002, state
      health departments (SHDs) received approximately 1 billion dollars in new federal
      funding to prepare for and respond to terrorism, infectious disease outbreaks,
      and other public health threats and emergencies. This funding is being used in
      part to improve epidemiologic and surveillance capabilities. To determine how
      states have used a portion of their new funding to increase ID epidemiology
      capacity, the Iowa Department of Public Health's Center for Acute Disease
      Epidemiology and the Iowa State University Department of Microbiology conducted
      two surveys of U.S. state epidemiologists during September 2000-August 2001 and
      October 2002-June 2003. This report summarizes the results of these surveys,
      which determined that although the number of SHD epidemiology workers assigned to
      ID and terrorism preparedness increased by 132%, concerns remained regarding the
      ability of SHDs to hire qualified personnel. These findings underscore the need
      to develop additional and more diverse training venues for current and future ID
      epidemiologists.

PMID- 14586301
TI  - West Nile virus activity--United States, October 23-29, 2003.
AB  - This report summarizes West Nile virus (WNV) surveillance data reported to CDC
      through ArboNET as of 3 a.m., Mountain Standard Time, October 29, 2003.

PMID- 14586302
TI  - The use of microabrasion to remove discolored enamel: a clinical report.
AB  - There is an ever-growing demand for esthetic dental treatment. Treatment
      modalities include crowns, bleaching, and ceramic or composite veneers. A more
      conservative treatment option, enamel microabrasion, may be indicated in certain
      clinical scenarios. The purpose of this clinical report is to describe the use of
      enamel microabrasion for a patient with discolored anterior teeth.

PMID- 14586303
TI  - Restoration of canine guidance on an occlusal splint using amalgam: a clinical
      report.
AB  - A primary consequence of sleep bruxism is severe tooth wear. Although an occlusal
      splint is able to protect teeth, grinding may continue on its surface. This
      clinical report describes an approach to restore canine guidance on an occlusal
      splint, with amalgam, for a patient with sleep bruxism. This procedure allowed
      maintenance of the canine guidance for a period of time longer than 3 months,
      postponing the fabrication of a new splint.

PMID- 14586304
TI  - A histologic study of bone response to bioactive glass particles used before
      implant placement: a clinical report.
AB  - This clinical report describes the microscopic analysis of the postextraction
      bone response to bioactive glass particles used prior to titanium implant
      placement, after a healing period of 6 months. The clinical and radiographic
      follow-up were performed over a 3-year period after implantation.

PMID- 14586305
TI  - Preformed acrylic cranial implants using fused deposition modeling: a clinical
      report.
AB  - Fabrication of acrylic cranial implants by conventional methods of moulage and
      mold formation may be difficult when the margin of the defect cannot be
      accurately detected. Three-dimensional anatomic models built by fused deposition
      modeling can serve as templates for the fabrication of custom acrylic implants
      for large or complicated cranial defects. Virtual mirror imaging of the
      contralateral nondefect side can facilitate the restoration of symmetry in
      appearance-sensitive areas. This clinical report presents a method for the
      fabrication of cranial implants for 2 patients using anatomic modeling
      technology.

PMID- 14586306
TI  - Evaluation of dental arch reproduction using three-dimensional optical
      digitization.
AB  - STATEMENT OF PROBLEM: Numerous investigations have been done to determine the
      most accurate method to reproduce a dental arch. Investigations have used
      different definitive cast configurations, materials, and measuring techniques to
      evaluate dimensional change, leaving clinicians undecided as to the most accurate
      method to reproduce a dental arch. PURPOSE OF STUDY: The purpose of this
      investigation was to evaluate the effect of impression tray selection on accuracy
      of reproductions of a dental arch using a 3-dimensional optical digitizer.
      MATERIALS AND METHODS: Impressions were made of a stone cast of a dental arch
      using vinyl polysiloxane impression material in custom and stock impression trays
      (n=12). Custom trays, designed with full palatal coverage, were fabricated on a
      separate standard stone cast using 2 layers of pink baseplate wax as the spacer
      and tissue stops on 1 anterior tooth and both first molar teeth. Impressions were
      poured with type IV gypsum and allowed to set with the tray inverted (n=5) or not
      inverted (n=5). The standard cast and resulting casts were digitized using an
      optical digitizer. Custom software was used to align and process the 3
      dimensional images created by the digitizer. Each image was superimposed onto the
      standard cast image, curves were created of the percent of points less than a
      defined distance between the 2 superimposed images, and the area under the curve
      was calculated. A weighted average area was calculated for each cast, and these
      values were analyzed using a 2-way ANOVA (alpha=.05). RESULTS: The main effect of
      tray type, laboratory setting technique, and the interaction between these 2
      characteristics was analyzed. None of these effects was significant. CONCLUSION:
      The differences in accuracy of reproductions of a dental arch, regardless of the
      impression and laboratory techniques, were not significant when evaluated using a
      3-dimensional optical digitizer.

PMID- 14586307
TI  - Influence of surface hardener on gypsum abrasion resistance and water sorption.
AB  - STATEMENT OF PROBLEM: Abrasion is a major concern when gypsum products are used
      for dies, leading to the frequent recommendation that surface hardeners should be
      used before waxing or scanning. PURPOSE: This study evaluated abrasion resistance
      and water sorption with 4 commonly used gypsum die materials with and without the
      application of surface die hardeners. MATERIAL AND METHODS: Three ADA Type IV
      (Vel-Mix, ResinRock, and Silky-Rock) and 1 Type V die material (Die-Keen) were
      evaluated for abrasion resistance after application of 2 surface hardeners
      (Permabond 910 cyanoacrylate and Clear Coat). Thirty specimens of each material
      were fabricated using an impression of a standard brass die machined with 1-mm
      high ridges, sloped 45 degrees. Gypsum materials were mixed according to
      manufacturers' recommendations and allowed to set 1 hour before separating. All
      replicated dies were allowed to bench set for 14 days before testing. One hour
      before testing, specimens were arbitrarily assigned to 1 of 3 treatment subgroups
      (n=10/group): no treatment (control), coated with Permabond 910, or coated with
      Clear Coat. In the coated groups, die hardener was painted over the grooves and
      air dried. Abrasion resistance (measured by weight loss) was evaluated using a
      reciprocal abrasion device in which a stylus applied a 50-g mass perpendicular to
      the ridges. Mass loss was determined using an analytical balance before and after
      each test cycle. Five sets of 20 unidirectional passes were made on each
      specimen. A scanning electron microscope was used to evaluate the surface of
      specimens in each treatment subgroup. Water sorption was also evaluated using 2
      Type IV (Silky-Rock, ResinRock) and 1 Type III (Microstone) gypsum materials.
      Specimen dies were separated 1 hour after pouring the impression and allowed to
      bench set 1 week before testing. Five specimens from each material group received
      a coating of a surface hardener 1 hour before testing. Specimens were placed in
      distilled water for 15 minutes and differences in mass were determined using an
      analytical balance before and after each test. A 2-way analysis of variance was
      completed followed by a Tukey post hoc test (alpha=.05). RESULTS: The 2-way
      analysis of variance revealed an interaction between product and surface coating
      (P=.0459). Given this interaction, the 12 combinations determined by surface
      treatment and material type were considered individually using the Tukey method.
      Vel-Mix, control (2.62 +/- 2.64 mg) had the most material loss and Vel-Mix, Clear
      Coat (0.48 +/- 0.29 mg) had the least material loss. Water sorption results
      indicated an interaction between the gypsum material and the surface treatment
      (P<.0001). The control groups of Microstone (299.2 +/- 49.6 mg) and Silky-Rock
      (159.0 +/- 8.5 mg) showed the most water sorption compared with the other
      treatment groups. CONCLUSIONS: This study demonstrated that a significant
      improvement in abrasion resistance occurred only with specific gypsum/surface
      hardener material combinations. Also, water sorption decreased significantly for
      Microstone and Silky-Rock gypsum materials when a surface hardener was used.

PMID- 14586308
TI  - Pulpal temperature increases with Er:YAG laser and high-speed handpieces.
AB  - STATEMENT OF PROBLEM: During tooth preparation, both high-speed handpieces and
      lasers generate heat, which, if not controlled, can cause pulpal necrosis.
      PURPOSE: The aim of this study was to compare temperature increases produced by a
      high-speed dental handpiece with those produced by a relatively new instrument,
      the Er:YAG (erbium: yttrium-aluminum-garnet) laser. MATERIALS AND METHODS: Thirty
      bovine mandibular incisors were reduced to an enamel/dentin thickness of 2.5 mm.
      Class V preparations were completed to a depth of 2.0 mm, measured with a caliper
      or by a mark on the burs. A thermocouple was placed inside the pulp chamber to
      determine temperature increases (degrees C). Analysis was performed on the
      following groups (n=10): Group I, high-speed handpiece without water cooling,
      Group II, high-speed handpiece with water cooling (30 mL/min), and Group III, the
      noncontact Er:YAG laser (2.94 microm at 350 mJ/10 Hz) with water cooling (4.5
      mL/min). The temperature increases were recorded by a computer linked to the
      thermocouples. The data were analyzed using the Kruskal-Wallis test. The Dunn
      multiple comparison test was used as post hoc test (alpha=.05). RESULTS: The
      average temperature rises were: 11.64 degrees C (+/- 4.35) for Group I, 0.96
      degrees C (+/- 0.71) for Group II, and 2.69 degrees C (+/- 1.12) for Group III.
      There were no statistical differences between Groups II and III; both II and III
      differed from Group I significantly (P=.000 and P=.002, respectively).
      CONCLUSION: The preparations made with the high-speed and the laser instrument
      generated similar heat increases under water cooling. Water cooling was essential
      to avoid destructive temperature increases when using both the high-speed
      handpiece and laser.

PMID- 14586310
TI  - In vitro marginal fit of three all-ceramic crown systems.
AB  - STATEMENT OF PROBLEM: Studies on marginal discrepancies of single restorations
      using various systems and materials have resulted in statistical inferences that
      are ambiguous because of small sample sizes and limited numbers of measurements
      per specimen. PURPOSE: The purpose of this study was to compare the marginal
      adaptation of single anterior restorations made using different systems. MATERIAL
      AND METHODS: The in vitro marginal discrepancies of 3 different all-ceramic crown
      systems (Celay In-Ceram, conventional In-Ceram, and IPS Empress 2 layering
      technique), and a control group of metal ceramic restorations were evaluated and
      compared by measuring the gap dimension between the crowns and the prepared tooth
      at the marginal opening. The crowns were made for 1 extracted maxillary central
      incisor prepared with a 1-mm shoulder margin and 6-degree tapered walls by
      milling. Thirty crowns per system were fabricated. Crown measurements were
      recorded with an optical microscope, with an accuracy of +/-0.1 microm, at 50
      points spaced approximately 400 microm along the circumferential margin. The
      criterion of 120 microm was used as the maximum clinically acceptable marginal
      gap. Mean gap dimensions and standard deviations were calculated for marginal
      opening. The data were analyzed with a 1-way analysis of variance (alpha=.05).
      RESULTS: Mean gap dimensions and standard deviations at the marginal opening for
      the incisor crowns were 87 +/- 34 microm for control, 83 +/- 33 microm for Celay
      In-Ceram, 112 +/- 55 microm for conventional In-Ceram, and 46 +/- 16 microm for
      the IPS Empress 2 layering technique. Significant differences were found among
      the crown groups (P<.05). Compared with the control group, the IPS Empress 2
      group had significantly smaller marginal discrepancies (P<.05), and the
      conventional In-Ceram group exhibited significantly greater marginal
      discrepancies (P<.05). There was no significant difference between the Celay In
      Ceram and the control group. CONCLUSION: Within the limitations of this study,
      the marginal discrepancies were all within the clinically acceptable standard set
      at 120 microm. However, the IPS Empress 2 system showed the smallest and most
      homogeneous gap dimension, whereas the conventional In-Ceram system presented the
      largest and more variable gap dimension compared with the metal ceramic (control)
      restoration.

PMID- 14586309
TI  - In vitro cytotoxicity of traditional versus contemporary dental ceramics.
AB  - STATEMENT OF PROBLEM: The biocompatibility of new dental ceramics has not been
      assessed with the same scrutiny as has been applied to alloys and composites.
      Yet, the biocompatibility of ceramics is critical to the long-term success of
      dental prostheses because ceramics are in close contact with oral tissues for
      extended periods. MATERIAL AND METHODS: Five dental ceramics (2 traditional
      feldspathic veneer porcelains [Vita Omega and Duceragold], 2 lithium disilicate
      pressable materials [Stylepress and Empress-2], and a pressable leucite-based
      material [Empress-1]) were tested for their ability to alter cellular
      mitochondrial dehydrogenase activity after fabrication using a tetrazolium assay,
      after aging for 2 weeks in a biologic solution and after post-aging polishing
      with either a fine diamond or diamond polishing paste. Cellular responses were
      compared with polytetrafluoroethylene controls (analysis of variance, Tukey
      pairwise post-hoc comparison, alpha=.05). RESULTS: The feldspathic porcelains
      caused only mild (<25% of controls) mitochondrial suppression regardless of aging
      or polishing. The pressable leucite-based material initially caused a 5%
      stimulation (not significant) of mitochondrial activity, which decreased
      significantly (P<.05) by 30% with aging to levels comparable to the feldspathic
      porcelains, and did not change with polishing. Both lithium disilicate materials
      caused an initial suppression of mitochondrial activity that decreased
      significantly with aging, but Empress-2 was severely cytotoxic initially (<20% of
      controls, P<.01), and became more cytotoxic again after polishing. Stylepress was
      less cytotoxic initially (85% of controls, not significant) and did not become
      cytotoxic again after polishing. CONCLUSIONS: Dental ceramics are not equivalent
      in their in vitro biologic effects, even within the same class of material, and
      biologic safety should not be assumed. Most ceramics caused only mild in vitro
      suppression of cell function to levels that would be acceptable on the basis of
      standards used to evaluate alloys and composites. However, 1 Li-disilicate
      material (Empress-2) exhibited cytotoxicity that would not be deemed biologically
      acceptable on the basis of prevailing empirical standards for dental alloys and
      composites.

PMID- 14586311
TI  - The influence of the veneering porcelain and different surface treatments on the
      biaxial flexural strength of a heat-pressed ceramic.
AB  - STATEMENT OF PROBLEM: The strength of all-ceramic restorations can be adversely
      affected by surface defects, leading to restoration failures. Additionally, when
      a 2-layer all-ceramic restoration is required for esthetic purposes, part of the
      stronger ceramic core material is replaced by veneering porcelain. PURPOSE: This
      study evaluated the effect of different surface treatments on the strength of a
      ceramic core material and veneering porcelain, as well as the influence of
      veneering porcelain on the strength of a 2-layer ceramic structure. MATERIAL AND
      METHODS: Fifty heat-pressed ceramic cores and 30 veneering porcelain discs (17 mm
      diameter x 2 mm) were made. From the ceramic core group, 20 discs were selected
      and reduced to a thickness of 1 mm and veneered with 1 mm of porcelain. These
      specimens were divided into 2 groups of 10 each. The remaining 30 ceramic core
      and the 30 veneering porcelain discs were divided into 2 sets of 3 equal sized
      groups (n=10). Ceramic core groups were prepared for testing having the following
      surfaces: airborne-particle abrasion, ground, and overglazed. Veneering porcelain
      groups were tested: as fired (no additional treatment), ground, and overglazed.
      Biaxial flexural strength was measured using the ball-on-ring test method. All
      specimens were loaded to fracture. One and 2-way analysis of variance were used
      to analyze the data (alpha=.05). RESULTS: The ceramic core discs were
      significantly (P=.001) stronger than the veneering porcelain discs for the
      airborne-particle abrasion, as-fired, and ground surface treatments (82 +/- 11
      MPa vs 51 +/- 8 MPa and 93 +/- 14 MPa vs 60 +/- 6 MPa, respectively). For the
      overglazed treatment, there was not a significant difference between the core
      (115 +/- 1 4 MPa) and the veneer materials (107 +/- 14 MPa). The ground 1-layer
      core was significantly (P=.015) stronger (93 +/- 14 MPa) than the 2-layer with
      the core tested in tension (72 +/- 19 MPa). There was no significant difference
      between 1-layer veneer overglazed (107 +/- 14 MPa) and 2-layer discs when tested
      with the veneer in tension (105 +/- 16 MPa). CONCLUSION: The overglazed surface
      treatment significantly improved the strength of the materials tested, as well as
      the strength of 2-layer discs with the veneer in tension. The veneering porcelain
      influenced the strength of 2-layer specimens only when tested with the ground
      ceramic core surface in tension.

PMID- 14586312
TI  - A review of selected dental literature on contemporary provisional fixed
      prosthodontic treatment: report of the Committee on Research in Fixed
      Prosthodontics of the Academy of Fixed Prosthodontics.
AB  - One goal of the American Academy of Fixed Prosthodontics is regularly to publish
      comprehensive literature reviews on selected topics germane to the discipline of
      fixed prosthodontics. The following report is the result of this goal and focuses
      on provisional fixed prosthodontic treatment. Major subtopics include materials
      science and clinical considerations involving natural teeth and dental implants.
      The interrelationship between provisional and definitive fixed prosthodontic
      treatment is multifaceted and significant. Provisional therapy involves numerous
      materials and techniques that require special knowledge and technical experience.
      In this analysis, technical, clinical, and investigational articles are detailed
      and presented as a comprehensive literature review to provide contemporary
      guidelines. Referenced publications were found by conducting a Medline search and
      were limited to peer-reviewed, English-language articles published from 1970 to
      the present. Materials used with provisional treatment are discussed in terms of
      clinical selection and the influence of their physical properties on treatment
      outcome. Specific product names and manufacturers are included in this report
      only when they are cited in the original referenced publications.

PMID- 14586313
TI  - In vitro wear of various orthotic device materials.
AB  - STATEMENT OF PROBLEM: Orthotic devices are advocated to decrease occlusal
      attrition caused by bruxism but tend to wear with time. PURPOSE: This study
      investigated the wear rate of various materials used to fabricate orthotic
      devices. MATERIAL AND METHODS: Five experimental groups (n=8) were studied:
      Splint Biocryl autopolymerized (SBA), Splint Biocryl autopolymerized plus
      additional heat and pressure (SBHP), Forestacryl autopolymerized (FA),
      Forestacryl autopolymerized plus additional heat and pressure (FHP), and Quick
      Splint 15-minute (QS), light-polymerized composite. Specimens were mounted to the
      base of a universal testing machine. A wear device using steatite balls and a
      load of 9.1 kg was positioned against the specimens, submerged in a 37 degrees C
      water bath and subjected to 2500 reciprocal cycles. Wear, in micrometers, was
      calculated as the maximum peak to valley measurement (Ry) using profilometry.
      Data were subjected to analysis of variance (ANOVA) and Tukey's HSD (alpha=.05).
      RESULTS: Mean acrylic wear in micrometers was as follows: FA 6.8 +/-3.0; FHP 7.1
      +/- 1.8; SBA 20.4 +/- 5.6; SBHP 23.7 +/- 7.8; and QS 23.8 +/- 6.9. One-way ANOVA
      detected significant differences between groups (P<.001); the Tukey honestly
      significant difference test determined that FA and FHP specimens were
      significantly more resistant to wear than all other specimens (P=.007).
      CONCLUSION: Differences in in vitro wear resistance among various orthotic device
      materials exist. The in vitro wear resistance among other autopolymerizing
      materials appears to be related to proprietary differences.

PMID- 14586314
TI  - A comparative analysis of optical and conventional axiography for the analysis of
      temporomandibular joint movements.
AB  - STATEMENT OF PROBLEM: Currently available systems for pantographic tracing are
      heavy, bulky, and can interfere with jaw movements. PURPOSE: This study describes
      the development and clinical application of optoelectronic axiography designed to
      overcome system inherent problems of conventional bulky frame-based registration
      axiography. The purpose of this study is the comparison of the newly developed
      system and conventional axiography. MATERIAL AND METHODS: Three-dimensional
      recordings of condylar pathways were acquired by means of infrared digitizers
      interfaced to newly developed software. Ten distinct curves in each of 10
      subjects were recorded by synchronous optoelectronic axiography (100 tracings)
      and by conventional axiography (100 tracings). Usually, two 3-dimensional (3D)
      light weight sensors are provisionally fixed to the facial surface of a maxillary
      and mandibular incisor by means of a single orthodontic bracket. To allow for
      direct comparison of all 100 pairs of curves in this study, the 3D sensors of the
      optoelectronic system were attached to the bulky double face-bow system of the
      axiograph. The conformity of tracings (protrusion, opening/closing, mediotrusion,
      and laterotrusion) was evaluated by means of correlation analysis. Resulting
      axiographic recordings from both systems were evaluated by 3 experts (dentists,
      experienced in axiographic investigations, who were blind to the source of the
      data), focusing on standardized qualitative criteria of the recordings
      (homogeneity/smoothness, pathway-characteristics, excursion, and left/right
      symmetry). After testing for normal distribution of the ratio scaled data (length
      of pathway, horizontal condylar inclination [HCI], Bennett angle) with the
      Kolmogoroff-Smirnov test (alpha=.01), axiographic curves were quantitatively
      compared by means of an intraclass correlation coefficient ([ICC] alpha =.01).
      The Wilcoxon test (alpha=.01) was used to evaluate equivalence of ordinally
      scaled values (homogeneity of tracings) and Cohen's Kappa was used to compare
      excursion and left/right symmetry. RESULTS: High correspondence between curves
      recorded by conventional and optoelectronic axiography was observed. The mean
      differences of lengths between the protrusive, opening/closing, and mediotrusive
      pathways were 0.0 mm, 0.6 mm, and 0.1 mm, respectively. Pathways and values for
      HCI were found highly correlated (pathways: 95% CI of ICC 0.9776-0.9908; HCI: 95%
      CI of ICC 0.8641-0.9597). The 95% CIs for differences of pathways, HCI-value, and
      Bennett angle were -0.1mm/0.3mm, -3.4 degrees/1.9 degrees, and -2.8 degrees/4.8
      degrees, respectively. Pathway characteristics also corresponded well (Cohen's
      Kappa: 0.73 for symmetric and 0.72 for asymmetric movements), 0.77 for left/right
      symmetry, whereas other characteristics showed less significant correlation
      (Cohen's Kappa of excursion: 0.21 for symmetric and 0.09 for asymmetric
      movements, homogeneity: 0.08 for symmetric and 0.15 for asymmetric movements).
      CONCLUSION: Within the limitations of this study, optoelectronic axiography
      proved to be an applicable, promising technique, leading to diagnostic
      interpretations equivalent (with respect to the CIs) to conventional axiography.

PMID- 14586315
TI  - A preplanned surgical obturator prosthesis for alternative resection lines in the
      anterior region.
AB  - A technique is described that enables adaptation of a surgical obturator to
      accommodate anterior teeth that may or may not be resected with the lesion at
      surgery. This is designed and fabricated by placing additional clasps on the
      teeth in question and providing for a clasp on one of the anterior teeth that can
      be determined at the time of surgery, thereby allowing anterior retention of the
      obturator immediately postoperatively. This technique is cost-effective and
      useful, especially if no prosthodontist is available at the time of surgery to
      perform obturator modifications.

PMID- 14586317
TI  - Menopausal hormone therapy informed consent.

PMID- 14586316
TI  - Use of dental floss in removing an inlay at trial evaluation.

PMID- 14586318
TI  - Toward a reduction of the global burden of cervical cancer.
AB  - Of the 190,000 deaths from cervical cancer that occur annually worldwide, the
      majority take place in developing countries. Recent advances in our understanding
      of the causes and natural history of cervical neoplasia and, in particular, the
      establishment of the central role of human papilloma virus (HPV) infection have
      created opportunities for the primary and secondary prevention of cervical
      cancer. In the future, prevention efforts will include the incorporation of HPV
      testing as an adjunct to or replacement for cytology-based screening programs and
      the use of recombinant DNA technologies for the development of prophylactic
      vaccines.

PMID- 14586319
TI  - New cervical cancer screening techniques.

PMID- 14586320
TI  - Awareness and concern about ovarian cancer among women at risk because of a
      family history of breast or ovarian cancer.
AB  - Research on women at risk for breast cancer because of family history suggests
      that a substantial proportion need education and counseling to assist them in
      their efforts to understand their risk of breast cancer and that some do not get
      appropriate breast cancer screening. Although women at high genetic risk for
      breast cancer are at elevated risk for ovarian cancer as well, few studies have
      examined these women's needs for education and counseling about ovarian cancer
      risk. This study examined awareness of ovarian cancer, perceived risk of breast
      and ovarian cancer, interest in genetic testing, and use of screening for breast
      and ovarian cancer in a population-based sample of women at high risk for breast
      and ovarian cancer because of a strong family history of cancer at one or both
      sites. We found that most high-risk women are not getting the information and
      care they need with respect to their risk for ovarian cancer. Almost 75% have not
      heard much about their risk for ovarian cancer. More than 90% failed to use 1 or
      another of 2 possible tests used for ovarian cancer screening regularly.

PMID- 14586321
TI  - Consumer knowledge and opinions of genetic testing for breast cancer risk.
AB  - Although clinical evidence shows the value of genetic testing for breast cancer
      risk, consumer opinion about the test-and its outcomes-may differ. We conducted
      focus groups with white and black women to assess consumer opinions about genetic
      testing for breast cancer risk. We conducted 5 focus groups with women between
      the ages of 30 and 79. Participants were not selected for personal or family
      history of breast cancer. The findings of these focus groups suggest that
      consumers' understandings of risk, genetics, and genetic testing can differ
      considerably from clinical definitions and interpretations. Clinical information
      appeared to be interpreted by participants based on personal experience and
      beliefs about genetics and disease causation. Our findings also suggest that many
      consumers have incomplete or erroneous knowledge about genetic testing (eg,
      whether the test should be repeated annually). Participants gave greater
      attention to the emotional and social consequences of positive test results than
      to their physical outcomes, suggesting that emotional and social issues may be
      more salient in decision making about whether to be tested. Sensitivity to the
      possibility that consumers may use nonclinical criteria to assess the value of
      genetic testing can help clinicians counsel women about testing and what actions
      to take after testing.

PMID- 14586322
TI  - Paternal age >or=40 years: an important risk factor for infertility.
AB  - OBJECTIVE: The purpose of this study was to examine the risk of infertility that
      is associated with paternal age, because this factor rarely has been
      investigated, whereas maternal age of >or=35 years is a well-known risk factor.
      STUDY DESIGN: This large, retrospective, population-based sample included 6188
      European women (from Denmark, Italy, Spain, Germany) aged 25 to 44 years who were
      selected randomly from census registers in 1991 through 1993. RESULTS: Among
      couples composed of a woman aged 35 to 39 years, risks were significantly higher
      when paternal age was >or=40 years than when paternal age was <40 years, with an
      adjusted odds ratio of 2.21 (95% CI, 1.13, 4.33) for delay in pregnancy onset
      (failure to conceive within 12 months) and of 3.02 (95% CI, 1.56, 5.85) for
      difficulties in having a baby (failure to conceive within 12 months or pregnancy
      not resulting in a live birth). CONCLUSION: Like maternal age of >or=35 years,
      paternal age of >or=40 years should be considered to be a key risk factor for
      infertility.

PMID- 14586323
TI  - Cervical incompetence prevention randomized cerclage trial: emergency cerclage
      with bed rest versus bed rest alone.
AB  - OBJECTIVE: The purpose of this study was to compare preterm delivery rates and
      neonatal morbidity/mortality rates for women with cervical incompetence with
      membranes at or beyond a dilated external cervical os that was treated with
      emergency cerclage, bed rest plus indomethacin, versus just bed rest. STUDY
      DESIGN: Women with cervical incompetence with membranes at or beyond a dilated
      external cervical os, before 27 weeks of gestation, were treated with antibiotics
      and bed rest and randomly assigned for emergency cerclage and indomethacin or bed
      rest only. RESULTS: Twenty-three women were included; 13 women were allocated
      randomly to the emergency cerclage and indomethacin group, and 10 women were
      allocated randomly to the bed rest-only group. Gestational age at time of
      randomization was 22.2 weeks in the emergency cerclage and indomethacin group and
      23.0 weeks in the bed rest-only group. Mean interval from randomization until
      delivery was 54 days in the emergency cerclage and indomethacin group and 20 days
      in the bed rest-only group (P=.046). Mean gestational age at delivery was 29.9
      weeks in the emergency cerclage and indomethacin group and 25.9 weeks in the bed
      rest-only group. Preterm delivery before 34 weeks of gestation was significantly
      lower in the emergency cerclage and indomethacin group, with 7 of 13 deliveries
      versus all 10 deliveries in the bed rest-only group (P=.02). CONCLUSIONS:
      Emergency cerclage, indomethacin, antibiotics, and bed rest reduce preterm
      delivery before 34 weeks compared with bed rest and antibiotics alone.

PMID- 14586324
TI  - Interleukin-1 receptor antagonist gene polymorphism and multifetal pregnancy
      outcome.
AB  - OBJECTIVE: The purpose of this study was to determine whether interleukin-1
      receptor antagonist and/or interleukin-1beta gene polymorphisms influence
      multifetal pregnancy outcome. STUDY DESIGN: Maternal and neonatal buccal swabs
      from 51 multifetal gestations were analyzed for interleukin-1 receptor antagonist
      and interleukin-1beta alleles. Outcome data were obtained subsequently. RESULTS:
      Fetal carriage of interleukin-1 receptor antagonist allele 1 was more than twice
      as prevalent as the carriage of allele 2. Preterm premature rupture of membranes
      was observed in 12 of 24 pregnancies (50.0%) in which 2 fetuses tested positive
      for interleukin-1 receptor antagonist allele 2, as opposed to only 3 of 27
      pregnancies (11.1%) in which 1 or neither fetus tested positive for interleukin-1
      receptor antagonist allele 2 (P=.005). Similarly, 20 of 26 neonates (76.9%) with
      documented morbidity tested positive for interleukin-1 receptor antagonist allele
      2, as compared with 36 of 78 neonates (46.2%) without morbidity (P=.007). Fetal
      or maternal interleukin-1beta polymorphisms or maternal interleukin-1 receptor
      antagonist polymorphisms were unrelated to pregnancy outcome. CONCLUSION: Fetal
      carriage of interleukin-1 receptor antagonist allele 2 was associated with both
      preterm premature rupture of membranes and neonatal morbidity in women with
      multifetal pregnancies.

PMID- 14586325
TI  - Interleukin-6 promoter -174 polymorphism and spontaneous preterm birth.
AB  - OBJECTIVE: We assessed the relationship between interleukin-6 (IL-6) promoter 
      174 polymorphism and spontaneous preterm birth (sPTB) less than 34 weeks and the
      relationship of polymorphism status with race. STUDY DESIGN: Polymerase chain
      reaction was used to evaluate DNA from 156 controls who delivered after
      spontaneous labor at term and 51 subjects who had sPTB less than 34 weeks.
      RESULTS: Among the 156 controls, the C/C variant was present in 30 (19.2%). Among
      the 51 subjects, the C/C variant was present in 2 (6.3%) (odds ratio 0.17, 95% CI
      0.04-0.74). Among white women, the C/C variant was present in 30 (27.2%) controls
      but only 2 (5.2%) cases. No African American women carried the C/C variant. The
      racial disparity was statistically significant. (P<.001) CONCLUSION: The IL-6
      promoter -174 allelic variant C/C is significantly less frequent among women with
      sPTB less than 34 weeks. There is a dramatic racial disparity in the distribution
      of allelic variants of this polymorphism.

PMID- 14586326
TI  - The clinical significance of detecting Ureaplasma urealyticum by the polymerase
      chain reaction in the amniotic fluid of patients with preterm labor.
AB  - OBJECTIVE: This study was undertaken to determine the clinical significance of a
      detection of Ureaplasma urealyticum by using the polymerase chain reaction (PCR)
      in the amniotic fluid of patients with preterm labor and intact membranes. STUDY
      DESIGN: Amniocentesis was performed in 257 patients with preterm labor and intact
      membranes. Amniotic fluid was cultured for aerobic and anaerobic bacteria as well
      as genital mycoplasmas. U urealyticum was detected by PCR using specific primers.
      Patients were divided into 3 groups according to the results of amniotic fluid
      culture and PCR for U urealyticum: those with a negative culture and negative PCR
      (n=228), those with a negative culture but positive PCR (n=6), and those with a
      positive culture regardless of the results of PCR (n=23). RESULTS: The prevalence
      of positive amniotic fluid culture was 9% (23 of 257). U urealyticum was detected
      by PCR in 6% (15 of 254) of cases. Of the 15 cases with positive PCR for U
      urealyticum, amniotic fluid culture was negative in 40% (6 of 15). Patients with
      a negative culture but positive PCR for U urealyticum had significantly shorter
      median amniocentesis-to-delivery interval and higher amniotic fluid interleukin-6
      and white blood cell count than those with a negative amniotic fluid culture and
      negative PCR (P<.01 for each). Patients with a positive PCR for U urealyticum but
      a negative amniotic fluid culture had a higher rate of significant neonatal
      morbidity than those with a negative culture and negative PCR (P<.05). However,
      no significant differences in perinatal outcome were observed between patients
      with a negative culture but positive PCR and those with a positive amniotic fluid
      culture. CONCLUSION: Patients with preterm labor and a positive PCR for U
      urealyticum but negative amniotic fluid culture are at risk for impending preterm
      delivery and adverse perinatal outcome.

PMID- 14586327
TI  - Uterine rupture, perioperative and perinatal morbidity after single-layer and
      double-layer closure at cesarean delivery.
AB  - OBJECTIVE: This study was undertaken to evaluate the risks and benefits of single
      layer uterine closure at cesarean delivery on the index and subsequent pregnancy.
      STUDY DESIGN: A retrospective study of women delivered of their first live-born
      infants by primary low transverse cesarean delivery (1989-2001) and their
      subsequent pregnancy at our institution was performed. RESULTS: Of 768 women
      studied, 267 had single-layer and 501 had double-layer uterine closures in the
      index pregnancy. Single-layer closure was associated with slightly decreased
      blood loss (646 vs 690 mL, P<.01), operative time (46 vs 52 minutes, P<.001),
      endometritis (13.5% vs 25.5%, P<.001), and postoperative stay (3.5 vs 4.1 days,
      P<.001). In the second pregnancy, prior single-layer closure was not associated
      with uterine rupture after a trial of labor (0% vs 1.2%, P=.30), or other
      maternal or infant morbidities. Prior single-layer closure was associated with
      increased uterine windows (3.5% vs 0.7%, P=.046) at subsequent cesarean delivery.
      CONCLUSION: Single-layer uterine closure is associated with decreased infectious
      morbidity in the index surgery, but not uterine rupture or other adverse outcomes
      in the subsequent gestation.

PMID- 14586328
TI  - Relationship of prenatal care and perinatal morbidity in low-birth-weight
      infants.
AB  - OBJECTIVE: Lack of or no prenatal care (NPC) is associated with preterm birth
      (PTB) and low birth weight (LBW). Our purpose was to determine whether LBW
      infants delivered after NPC have worse outcomes than LBW infants with prenatal
      care (PC). STUDY DESIGN: Eight thousand sixty-five consecutive women delivered at
      six hospitals in Shelby County, Tenn, were evaluated regarding clinical
      characteristics and perinatal outcomes depending on the occurrence of PC. Infant
      and LBW infant outcomes were evaluated on the basis of the occurrence of PC.
      Multivariate analysis was performed for neonatal outcomes adjusting for race,
      plurality, antenatal steroids, amnionitis, and ponderal index. A P value less
      than .05 was considered significant. RESULTS: NPC women were more likely
      multiparous (80% vs 65%), African American (70% vs 61%), and uninsured (25% vs
      4%), P<.0001 for each. PTB (36% vs 15%) and LBW (22% vs 12%) were more common
      with NPC, P<.0001 for each. Women with NPC had more advanced cervical dilation
      (ACD) greater than 4 cm (ACD: 63% vs 39%) and more amnionitis on admission (2% vs
      1%), P<or=.001 for each, and had more fetal distress in labor, P=.02. NPC infants
      had increased mortality, respiratory distress syndrome, intraventricular
      hemorrhage, retinopathy, and bronchopulmonary dysplasia. Among LBW infants, NPC
      was associated with premature rupture of membranes, antepartum hemorrhage,
      amnionitis, and ACD. Controlling for other factors, NPC LBW infants had increased
      mortality (17% vs 9%), respiratory distress syndrome (31% vs 24%),
      intraventricular hemorrhage (10% vs 5%), retinopathy (13% vs 9%), and
      bronchopulmonary dysplasia (11% vs 7%), P<or=.04 for each. CONCLUSION: In
      addition to increasing PTB and LBW, NPC is associated with increased perinatal
      morbidity and mortality among LBW infants after controlling for confounding
      factors.

PMID- 14586329
TI  - Specialized prenatal care and maternal and infant outcomes in twin pregnancy.
AB  - OBJECTIVE: This study was undertaken to evaluate the effect of a prenatal
      nutrition and education program on twin pregnancy, neonatal, and early childhood
      outcomes. STUDY DESIGN: This prospective intervention study of women who
      participated in a specialized program (Program Pregnancies) versus
      nonparticipants included twice-monthly visits, dietary prescription of 3000 to
      4000 kcal per day, multimineral supplementation, and patient education. RESULTS:
      Program Pregnancies were associated with improved pregnancy outcomes
      (preeclampsia, adjusted odds ratio [AOR] 0.41, 95% CI, 0.23-0.75; preterm
      premature rupture of membranes, AOR 0.35, 95% CI, 0.20-0.60; delivery <36 weeks,
      AOR 0.62, 95% CI, 0.43-0.89; low birth weight, AOR 0.42, 95% CI, 0.29-0.61),
      significantly longer gestations (+7.6 days), higher birth weights (+220 g), lower
      neonatal morbidity (retinopathy of prematurity, necrotizing enterocolitis,
      intraventricular hemorrhage, or ventilator support, AOR 0.44, 95% CI, 0.31-0.62),
      length of stay (-5.3 days), and cost per twin (-14,023 dollars). Through 3 years
      of age, program children were significantly less likely to be rehospitalized (AOR
      0.31, 95% CI, 0.11-0.91) or to be developmentally delayed (AOR 0.65, 95% CI, 0.44
      0.96). CONCLUSION: Program participation was associated with improved outcomes at
      birth and through age 3 years.

PMID- 14586330
TI  - Adverse pregnancy outcomes in snuff users.
AB  - OBJECTIVE: The purpose of the study was to evaluate the effects of smokeless
      tobacco use during pregnancy. STUDY DESIGN: We examined birth weight, preterm
      delivery, and preeclampsia in women who were delivered of singleton, live-born
      infants in Sweden from 1999 through 2000. For each snuff user, 10 cigarette
      smokers and 10 tobacco nonusers were selected randomly. RESULTS: After
      exclusions, 789 snuff users, 11,240 smokers, and 11,495 nonusers remained.
      Compared with nonusers, adjusted mean birth weight was reduced in snuff users by
      39 g (95% CI, 6-72 g) and in smokers by 190 g (95% CI, 178-202 g). Preterm
      delivery was increased in snuff users and smokers (adjusted odds ratios, 1.98
      [95% CI, 1.46-2.68] and 1.57 [95% CI, 1.38-1.80], respectively). Preeclampsia was
      reduced in smokers (adjusted odds ratio, 0.63; 95% CI, 0.53-0.75) but increased
      in snuff users (adjusted odds ratio, 1.58; 95% CI, 1.09-2.27). CONCLUSION: Snuff
      use was associated with increased risk of preterm delivery and preeclampsia.
      Snuff does not appear to be a safe alternative to cigarettes during pregnancy.

PMID- 14586332
TI  - Neuropeptide Y administered into cerebral ventricles stimulates sucrose ingestion
      in the near-term ovine fetus.
AB  - OBJECTIVE: In adults, nutrient intake is controlled by opposing actions of
      appetite stimulants (eg, neuropeptide Y [NPY]) and suppressors (eg, leptin).
      Because NPY may exert a preferential role in mediating adult carbohydrate intake,
      we sought to determine the effect of central NPY on near-term fetal carbohydrate
      ingestion. STUDY DESIGN: Five pregnant ewes and fetuses were prepared with fetal
      vascular, sublingual, and intracerebroventricular catheters, electrocorticogram,
      and esophageal electromyogram electrodes and studied at 131+/-2 days' gestation.
      After a 2-hour baseline period, 10% sucrose was infused sublingually for the
      duration of the study. At 4 hours' time, NPY was injected into the fetal cerebral
      ventricles and fetal swallowing monitored for an additional 6 hours. RESULTS:
      During the basal period, mean (+/-SEM) swallowing averaged 0.8+/-0.1 swallows per
      minute. Fetal swallowing increased significantly in response to sublingual
      sucrose (1.3+/-0.1 swallows/min, P=.001), and further significantly increased at
      4 to 6 hours after NPY injection into the cerebral ventricles (1.8+/-0.3,
      P=.001). CONCLUSION: These results indicate central NPY stimulation of fetal
      ingestion beyond that resulting from sublingual 10% sucrose. The in utero
      development of NPY-induced ingestive behavior may be in preparation for high
      neonatal caloric intake.

PMID- 14586331
TI  - The influence of obesity and gestational diabetes mellitus on accretion and the
      distribution of adipose tissue in pregnancy.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effect of pregravid
      obesity and gestational diabetes mellitus (GDM) on the longitudinal accretion and
      distribution of adipose tissue in pregnancy. STUDY DESIGN: Women with normal
      glucose tolerance and GDM were evaluated before conception, early (12-14 weeks)
      and late (33-36 weeks) in gestation. Fat mass, lean body mass, and percent body
      fat were assessed longitudinally with hydrodensitometry. Serial biceps, triceps,
      subscapular, iliac, costal, mid thigh, and lower thigh skinfold measurements
      quantified the changes in fat mass distribution. Pregravid obesity was defined as
      >25% body fat. RESULTS: Subjects included 19 patients with GDM (5 lean women, 14
      obese women), and 33 patients with normal glucose tolerance (controls; 12 lean
      women, 21 obese women). GDM and control subjects were similar in pregravid
      percent body fat (29.6% vs 27.9%, P=.47) and fat mass (20.8 kg vs 18.2 kg,
      P=.37). Values for subjects with GDM and controls were also similar in terms of
      percent body fat, fat mass, and weight gained (change in percent body fat, -0.7%
      vs 1.9% [P=.07]; change in fat mass, 3.8 kg vs 5.0 kg [P=.08]; change in weight,
      12.0 kg vs 13.2 kg [P=.35]). Lean subjects gained more percent body fat compared
      with obese subjects (change in percent body fat, 3.3% vs 0.1% [P=.004]) but
      gained similar amounts of fat mass (change in fat mass, 4.7 kg vs 4.2 kg
      [P=.58]), lean body mass (7.6 kg vs 8.8 kg [P=.18]), and weight (change in
      weight, 12.3kg vs 13.0 kg [P=.61]) The distribution of adipose tissue that was
      accumulated as estimated with skinfold measurements was similar between patients
      with GDM and glucose tolerance (P>.05 for all changes in skinfolds), but
      significantly different between lean and obese patients (P<.05 for all changes in
      skinfolds). Lean women gained a predominance of adipose tissue peripherally over
      that in obese women. CONCLUSION: Lean women accrue significantly more fat mass
      than obese women, regardless of glucose tolerance. Pregestational obesity rather
      than GDM influences the distribution of adipose accretion.

PMID- 14586333
TI  - Development of ovine fetal ileal motility: role of muscarinic receptor subtypes.
AB  - OBJECTIVE: In the preterm human fetus, immaturity of gastrointestinal (GI)
      motility contributes to impairment of oral feeding and an increased risk of
      necrotizing enterocolitis. In view of the limited knowledge of fetal GI motility
      development, and the primary role of the muscarinic system in adult GI motility,
      we examined the development of GI muscarinic receptor subtypes associated with
      ileal motility. STUDY DESIGN: Ovine term fetal, newborn, and pregnant adult ileal
      longitudinal muscle contractile responses to muscarinic agonists (bethanechol)
      and muscarinic nonspecific (atropine) and subtype specific-antagonists (M1-M4)
      were examined in organ baths. Immunohistochemical analysis of ileal muscle
      muscarinic receptor subtypes was correlated with contractile responses. RESULTS:
      Bethanechol induced a concentration-dependent ileal contraction at all 3 age
      groups. Adult ileal maximal tension was 2-fold higher than that of the fetus and
      newborn, while 50% effective concentration (EC(50)) was similar at all ages.
      Atropine (10(-6)mol/L) inhibited contractility in fetal (67%+/-7%), newborn
      (82%+/-5%), and adult (97%+/-2%) in an age-dependent manner. The M3 antagonist
      exhibited robust inhibition at all age groups while the M2 antagonist
      demonstrated enhanced inhibition in the fetus. Immunohistochemical analysis
      indicated coexpression of subtype receptors in fetal, newborn, and adult ileal
      smooth muscle with increasing expression with advancing age. CONCLUSION: These
      results demonstrate a specific developmental pattern of muscarinic receptor
      subtype expression. Knowledge and/or alterations of GI motility regulation may
      aid in the treatment of the preterm fetus or newborn.

PMID- 14586334
TI  - The role of fetal breathing motions compared with gasping motions in pulmonary
      airway uptake of intra-amniotic iron dextran.
AB  - OBJECTIVE: We hypothesized that normal fetal breathing, not acute asphyxial
      gasping, results in the movement of iron dextran from the amniotic cavity into
      the fetal lungs. In addition, the amount of iron dextran moving into the fetal
      lungs is cumulative with time. STUDY DESIGN: Twelve pregnant New Zealand White
      rabbits at 25 days of gestation were sedated and underwent ultrasound-guided
      injections of iron dextran into the amniotic cavities of the rabbit fetuses in
      both horns of each pregnant doe. Oxygen saturation was maintained at >90% in the
      pregnant does. The 12 does were then equally assigned to four groups on the basis
      of the duration of fetal exposure to the dextran (0, 8, 16, and 24 hours). At the
      end of each time point, one half of the fetuses received an intracardiac
      injection of potassium chloride to induce gasping just before necropsy. Gasping
      was confirmed by ultrasound scanning. At necropsy, the fetal lungs were evaluated
      grossly and underwent histomorphometry for iron distribution and quantification
      in the fetal airways. RESULTS: In the animals that received iron dextran, there
      was no significant difference in iron accumulation at any time point between
      those animals that did and did not receive potassium chloride, which suggests
      that acute gasping does not increase the accumulation of amniotic fluid
      substances in the lungs. The amount of iron in the fetal airways increased
      significantly with progressive length of exposure. CONCLUSION: We conclude that
      normal fetal breathing, not acute asphyxial gasping, resulted in the movement of
      intra-amniotic iron dextran into the fetal lungs and that the amount of
      substances that move into the fetal lungs accumulated with time.

PMID- 14586336
TI  - Maternal cerebral blood flow changes in pregnancy.
AB  - OBJECTIVE: This study was undertaken to determine blood flow changes in the large
      cerebral arteries during normal pregnancy. STUDY DESIGN: Ten healthy pregnant
      volunteers underwent velocity-encoded phase contrast magnetic resonance imaging
      at 4 time intervals: 14 to 16, 28 to 32, and 36 to 38 weeks' gestation, and at 6
      to 8 weeks' postpartum. Analysis consisted of serial paired Student t tests, with
      P<.05 considered significant. RESULTS: By using postpartum values for comparison,
      cerebral blood flow decreased by 14 to 16 weeks in the middle cerebral artery
      (P<.001), but was not significantly changed in the posterior cerebral artery.
      Significant decreases occurred in both the middle (P<.0001) and posterior
      (P=.002) cerebral arteries in late pregnancy. CONCLUSION: An approximately 20%
      reduction in large artery cerebral blood flow occurs during normal pregnancy,
      secondary to changes in velocity, whereas the area of these vessels remains
      unchanged. These findings may represent generalized vasodilatation of downstream
      resistance arterioles, assuming constant blood flow at the tissue level.

PMID- 14586335
TI  - Platelet-activating factor antagonist WEB-2170 inhibits lipopolysaccharide
      induced, but not antiprogestin-induced, preterm cervical ripening in timed
      pregnant rats.
AB  - OBJECTIVE: The purpose of this study was to determine whether the platelet
      activating factor antagonist WEB-2170 inhibits preterm cervical ripening induced
      by lipopolysaccharide or by antiprogestin RU 486. STUDY DESIGN: Timed-pregnant
      rats were killed on day 16 after treatment with (1) WEB-2170, lipopolysaccharide,
      lipopolysaccharide plus WEB-2170, or vehicle control and (2) with WEB-2170, RU
      486, RU 486 plus WEB-2170, or vehicle control. Cervical ripening was assessed by
      light-induced fluorescence and resistance to stretch. Statistics were assessed by
      1-way analysis of variance followed by Tukey-test (P <.05). RESULTS: Light
      induced fluorescence and resistance to stretch were significantly lower in the
      lipopolysaccharide-treated and in the RU486-treated animals compared with vehicle
      control (lipopolysaccharide:light-induced fluorescence, 7.0+/-0.6 vs 12.8+/-0.8
      [P=.001]; resistance to stretch, 0.41+/-0.03 N/mm vs 0.54+/-0.04 N/mm [P <.05];
      RU486:light-induced fluorescence, 9.6+/-0.6 vs 11.7+/-0.6 [P <.05]; resistance to
      stretch, 0.28+/-0.06 N/mm vs 0.61+/-0.02 N/mm [P <.001]). Compared with vehicle
      control, WEB-2170 alone did not alter cervical light-induced fluorescence or
      resistance to stretch. Although WEB-2170 significantly blocked cervical ripening
      after lipopolysaccharide administration (light-induced fluorescence, 11.3+/-1.3
      [P <.05]; resistance to stretch, 0.61+/-0.04 [P <.01]), WEB-2170 did not inhibit
      the RU 486-induced cervical ripening. CONCLUSION: Although infection-related
      cervical ripening is inhibited by platelet-activating factor antagonists, the
      physiologic process of cervical ripening appears to be unaffected. Platelet
      activating factor inhibition may be of clinical value in the infection-related
      pathologic processes that are responsible for premature cervical ripening.

PMID- 14586337
TI  - Multiple-marker screening in human immunodeficiency virus-positive pregnant
      women: Screen positivity rates with the triple and quad screens.
AB  - OBJECTIVE: The study was undertaken to determine the screen-positive rates of
      multiple-marker screening tests in pregnant women who are positive for human
      immunodeficiency virus (HIV) at our institution for open neural tube defects and
      aneuploidy, for both triple (alpha-fetoprotein, human chorionic gonadotropin
      [hCG], unconjugated estriol) and quad (alpha-fetoprotein, hCG, unconjugated
      estriol, inhibin A) screens, and to compare these rates with a matched control
      group. STUDY DESIGN: A 1:1 matched case-control study was performed comparing
      multiple marker screening test results in 34 HIV-positive women with age- and
      race-matched HIV-negative controls. Individual serum markers and screen positive
      rates for both the triple and quad screens were compared among the cases and
      controls. RESULTS: In each group, there were 19 women with triple screens and 15
      with quad screens. Serum hCG multiples of the median were significantly higher in
      the HIV-positive compared with the HIV-negative women (P=.033). There was no
      difference in screen positive rates between the cases and controls using the
      triple screen, but there was a significantly higher overall screen positive rate
      in the HIV-positive group when the quad screen was used (33% vs 7%, P=.046).
      CONCLUSION: There is a significantly higher rate of overall quad screen
      positivity on multiple-marker screening among HIV-positive women compared with a
      matched control group.

PMID- 14586338
TI  - Down syndrome screening using race-specific femur length.
AB  - OBJECTIVE: The study was undertaken to evaluate the influence of maternal race on
      fetal femur length when screening for Down syndrome. STUDY DESIGN: We reviewed
      our patient databases to obtain fetal biometry from 15 to 22 weeks' gestation,
      maternal race, and cases of Down syndrome. Institution and race-specific
      regression lines for femur length (FL) to biparietal diameter (BPD) were created.
      The efficiency of using published expected FL was compared with our institution
      and race-specific regression in screening for Down syndrome. RESULTS: There were
      4350 African American, 4271 white, 2315 Hispanic, and 654 Asian subjects and 42
      cases of Down syndrome (1:276) included in the study. Our institutionally derived
      regression for FL by BPD had an R(2) of 0.82. Regression lines for FL by BPD
      generated by race had an R(2) of 0.86, 0.84, 0.83, and 0.80 for African American,
      Hispanic, Asian, and white subjects, respectively. The race-specific regression
      was no better than institution-specific data. CONCLUSION: Using institution
      specific FL was more efficient in screening for Down syndrome than published
      expected FL; race-specific analysis did not improve efficiency.

PMID- 14586339
TI  - Prenatal screening for Down syndrome in England and Wales and population-based
      birth outcomes.
AB  - OBJECTIVE: Whether the introduction of antenatal screening for Down syndrome in
      England and Wales with serum biochemistry or ultrasound has led to improvements
      in patient outcomes is unknown. The purpose of this study was to relate pregnancy
      outcomes to the dominant method used for prenatal Down syndrome screening. STUDY
      DESIGN: For the years 1989 through 1999, England and Wales were divided into
      geographically defined areas where specific hospitals, health authorities, and
      cytogenetic laboratories provided maternity care for well-defined populations.
      For each year from 1989 through 1999, the dominant Down syndrome screening method
      that was used in each area was determined. Outcomes for area-years that used
      serum biochemistry or ultrasound (first or second trimester) were compared with
      area-years that used advanced maternal age as the dominant screening method. The
      percent of Down syndrome cases that were diagnosed prenatally (effectiveness) and
      the number of invasive prenatal tests that were performed to diagnose each Down
      syndrome case prenatally (efficiency) were compared. RESULTS: There were
      5,980,519 births and 335,184 referrals for prenatal karyotyping (amniocentesis
      and chorionic villus sampling) that occurred in the area-years studied, of which
      12,047 pregnancies were diagnosed as Down syndrome; 5393 cases of Down syndrome
      (45%) were diagnosed prenatally. Invasive testing increased from 4.4% of
      pregnancies in 1989 to 6.4% in 1997 and declined slightly in 1999 (5.8%).
      Prenatal diagnosis of Down syndrome cases rose from 28% in 1989 to 53% in 1999,
      and the number of invasive tests that were performed to diagnose each Down
      syndrome case fell from 89.7 to 47.7 (P [for trend]<.0001). Areas with serum or
      ultrasound as the dominant screening method detected 50% more Down syndrome cases
      in prenatally (52% and 53% vs 36%; P<.0001) and performed fewer invasive
      procedures to diagnose each Down syndrome case (60.7 and 52.0 vs 88.0; P<.0001)
      compared with areas in which advanced maternal age screening was dominant,
      despite serving populations with similar mean/median maternal ages. CONCLUSION:
      In clinical practice, screening programs for Down syndrome that were based on
      maternal serum biochemistry or ultrasound were more effective and efficient than
      the screening programs that used advanced maternal age alone.

PMID- 14586340
TI  - Ultrasound assessment of the fetal middle cerebral artery peak systolic velocity:
      A comparison of the near-field versus far-field vessel.
AB  - OBJECTIVE: Doppler assessment of the fetal middle cerebral artery peak systolic
      velocity may obviate the need for more invasive procedures in the alloimmunized
      patient. The purpose of this study was to compare middle cerebral artery peak
      systolic velocity measurements in the near field and far field. STUDY DESIGN:
      Patients between 16 and 42 weeks of gestation with normal fetuses were eligible
      (n=151). Peak systolic velocity measurements were obtained at the proximal
      portion of each middle cerebral artery at its origin in the internal carotid
      artery, as well as the most distal portion before its division, for a total of 4
      measurements per fetus. Comparisons were made among the 4 locations and the data
      were analyzed using a mixed-model analysis of variance adjusted for gestational
      age. Results were presented using both P values and 95% CIs. P values <.05 were
      considered statistically significant. Where appropriate, P values and 95% CIs
      were adjusted using the Tukey multiple comparison procedure. A subanalysis was
      performed using 11 patients to assess interobserver reliability, which was
      calculated using the intraclass correlation coefficient (ICC). RESULTS: All four
      measurements were obtained for 120 fetuses (79%). The mean gestational age was
      27.0 weeks. Statistically significant differences were noted between distal sites
      (95% CI, -0.05 to 0.01; P<.01) as well as the two sites on each vessel (95% CI,
      0.03-0.07 and 0.07-0.12; P<.001 for both vessels). There was no significant
      difference between the two proximal locations (95% CI, -0.01 to 0.03; P=0.77).
      CONCLUSION: By which of the 2 vessels the fetal middle cerebral artery peak
      systolic velocity is affected is selected, as well as the location on the vessel.
      If the near-field proximal site cannot be interrogated, the far-field proximal
      site may be the best alternative.

PMID- 14586341
TI  - Use of fetal magnetic resonance imaging in patients electing termination of
      pregnancy by dilation and evacuation.
AB  - OBJECTIVE: The purpose of this study was to determine whether magnetic resonance
      imaging of the fetal brain before dilation and evacuation enhances diagnosis when
      equivocal ultrasound findings and disrupted autopsy specimens exist. STUDY
      DESIGN: Patients with equivocal fetal brain abnormalities on ultrasound
      examination who were considering termination of pregnancy were evaluated
      retrospectively. Abdominal and pelvic magnetic resonance imaging was performed
      for further evaluation, and orthogonal fetal brain images were obtained. A
      multidisciplinary team reviewed all cases and discussed the findings, possible
      causes, and recurrence risks with each patient. RESULTS: Seven patients with
      fetal brain anomalies underwent magnetic resonance imaging before dilation and
      evacuation. Magnetic resonance imaging diagnoses included intracranial
      hemorrhages, semilobar holoprosencephaly, intracranial teratoma, multiple
      cerebral infarcts, and unilateral cerebellar hypoplasia. In all cases, magnetic
      resonance imaging provided valuable information and helped distinguish possible
      genetic syndromes from likely sporadic disorders of brain development.
      CONCLUSION: Magnetic resonance imaging can provide insight into diagnosis, cause,
      and recurrence risks for patients who choose dilation and evacuation because of
      fetal brain abnormalities.

PMID- 14586342
TI  - Prognostic factors associated with antenatal subchorionic echolucencies.
AB  - OBJECTIVE: This study was undertaken to determine prognostic factors in
      pregnancies with a subchorionic echolucency. STUDY DESIGN: One hundred twenty
      nine pregnancies with a subchorionic echolucency detected by ultrasound in our
      unit were identified. Ultrasound reports were reviewed for subchorionic
      echolucency location, size, gestational age, amniotic fluid volume, and fetal
      abnormalities. Adverse outcomes evaluated were pregnancy loss before 24 or 37
      weeks (PTD) and intrauterine growth restriction. Medical records were reviewed
      for antenatal complications and neonatal outcomes. RESULTS: There were 7 (5.4%)
      pregnancy losses before 24 weeks and 24 (18.6%) pregnancies complicated by PTD.
      Of the 122 pregnancies reaching viability, those complicated by antepartum
      bleeding were more likely to deliver prematurely than those without bleeding,
      (26.6% vs 7.0%, P=.009). Maximum area of subchorionic echolucency, gestational
      age at subchorionic echolucency detection, amniocentesis, maternal age, and
      parity were not associated with PTD. CONCLUSION: Patients with subchorionic
      echolucency appear to have a high incidence of PTD. Bleeding appears to be a
      reliable prognostic indicator.

PMID- 14586343
TI  - Feasibility of the fetal anatomic and maternal pelvic survey by magnetic
      resonance imaging at term.
AB  - OBJECTIVE: This study was undertaken to determine which nonbiometric components
      of the American College of Obstetricians and Gynecologists recommended ultrasound
      fetal anatomic and maternal pelvic survey can be evaluated by fast acquisition
      magnetic resonance (MR) imaging in the term fetus. STUDY DESIGN: Nonbiometric
      components of the fetal survey were retrospectively evaluated by fast acquisition
      MR images. Thirteen components were assessed, including fetal number,
      presentation, placental location, qualitative assessment of amniotic fluid, and
      the maternal pelvis (n=5). The fetal anatomy included bilateral cerebral
      ventricles, spine, bilateral kidneys, stomach, bladder, cord insertion, sex, and
      four-chamber view of the heart (n=8). Studies were performed before delivery and
      neonatal outcomes were reviewed. RESULTS: All 50 neonates were normal at follow
      up. A total of 94% (702 of 750) of the components were assessed by MR imaging.
      CONCLUSION: Fetal MR imaging can assess 94% of the American College of
      Obstetricians and Gynecologists recommended ultrasound fetal and pelvic anatomic
      survey. If the heart is excluded, this increases to 99%.

PMID- 14586344
TI  - Conventional management of maternal red cell alloimmunization compared with
      management by Doppler assessment of middle cerebral artery peak systolic
      velocity.
AB  - OBJECTIVE: This study was undertaken to compare management of red blood cell
      alloimmunization by Doppler measurement of middle cerebral artery peak systolic
      velocity (MCA-PSV) to conventional management with amniocentesis. STUDY DESIGN: A
      historical cohort of 28 fetuses at risk for anemia caused by red blood cell
      alloimmunization was followed between 1999 and 2002 at a single institution. The
      decision to perform percutaneous umbilical cord blood sampling (PUBS) was based
      on conventional management. MCA-PSV Doppler was measured before amniocentesis or
      PUBS but not used clinically. RESULTS: Twenty-eight fetuses were followed up: 4
      had severe anemia, 1 had moderate anemia, 3 had mild anemia, and 20 were
      nonanemic. Conventional management had a sensitivity and positive predictive
      value for moderate-to-severe anemia of 80% and 44%, with a false-positive rate of
      56%. In the same patients, MCA-PSV Doppler had a sensitivity and positive
      predictive value for moderate-to-severe anemia of 100% and 71%, with a false
      positive rate of 28%. CONCLUSION: Compared with conventional management, MCA-PSV
      Doppler may have a better predictive accuracy for moderate-to-severe fetal anemia
      in red blood cell alloimmunization. Management by MCA-PSV Doppler may eliminate
      the need for amniocentesis and reduce the number of PUBS performed in red blood
      cell-alloimmunized pregnancies.

PMID- 14586345
TI  - Doppler predictors of adverse neonatal outcome in the growth restricted fetus at
      34 weeks' gestation or beyond.
AB  - OBJECTIVE: The study was undertaken to assess whether prenatal Doppler variables
      can identify cases of fetal growth restriction (FGR) approaching term who are at
      risk for adverse neonatal outcome. STUDY DESIGN: From a cohort of FGR cases
      delivered at >or=34 weeks, fetal biometry and pulsatility indices (PI) of fetal
      arteries obtained less than 2 weeks before delivery were related to adverse
      neonatal outcome, defined as admission to the neonatal intensive care unit (NICU)
      for indications other than low birth weight alone. RESULTS: Stepwise regression
      analysis showed that after controlling for gestational age at delivery and fetal
      biometry, only the last umbilical artery (UA) PI percentile was significantly
      predictive of adverse neonatal outcome (odds ratio=1.02, 95% CI 1.01-1.03,
      P=.02). Receiver operating characteristic curve analysis identified a UA PI at
      the 65th percentile as optimal predictor of adverse neonatal outcome
      (sensitivity=60%, false-positive rate=30%). CONCLUSION: In FGR cases delivered at
      >/=34 weeks' gestation, Doppler PI at the UA independently predicts the
      likelihood of admission to the NICU for reasons other than low birth weight
      alone.

PMID- 14586346
TI  - Minimizing red blood cell contamination while isolating mononuclear cells from
      whole blood: the next step for the treatment of severe hemolytic disease of the
      fetus/newborn.
AB  - OBJECTIVE: We examined whether mononuclear cell purification of human blood could
      be done while minimizing contamination with RhD-positive red blood cells to treat
      hemolytic disease of the fetus/newborn that was caused by rhesus disease. STUDY
      DESIGN: Whole blood from 16 individuals who tested rhesus positive was diluted
      and centrifuged over a Ficoll gradient. The cell pellet was incubated with red
      blood cell lysis buffer, divided into three samples, and analyzed for cell count,
      mononuclear cell yield, and RhD-positive red cell contamination by flow
      cytometry. RESULTS: Mean RhD-positive red cell contamination was 0.24% (range, 0%
      1.9%). The average yield of mononuclear cells was 11.5% (range, 1.8%-23.6%).
      Through regression analysis, 34 to 180 mL of paternal whole blood would be
      necessary to achieve an antigen load that is sufficient for an HLA antibody
      response. CONCLUSION: Purification of human blood is possible to produce
      reasonable mononuclear cell yields with minimal rhesus activity, which makes
      paternal leukocyte therapy a plausible treatment for severe rhesus
      alloimmunization.

PMID- 14586347
TI  - Comparison of magnetic resonance imaging to ultrasound in the estimation of birth
      weight at term.
AB  - OBJECTIVE: This study was undertaken to compare magnetic resonance (MR) and
      ultrasound (US) fetal weight estimates obtained immediately before delivery with
      birth weight. STUDY DESIGN: Eighty women scheduled for a cesarean delivery
      underwent a fast acquisition MR and US for fetal weight estimation within 3 hours
      of delivery. Prospective MR calculation was based on the equation 0.12+1.031
      g/mLxfetal volume (mL)=MR weight (g). US fetal weight estimation was calculated
      by the formula by Hadlock et al. Estimations were compared with birth weight.
      RESULTS: Correlation (95% CI) between birth weight and MR weight is 0.95 with a
      mean absolute error of 129 g (105-155) compared with the correlation between
      birth weight and US of 0.85 with a mean absolute error of 225 g (186-264). The
      correlation for birth weight and MR imaging is significantly greater than that of
      birth weight and US, P<.001. CONCLUSION: Birth weight estimation is more accurate
      by MR imaging than by US in term infants.

PMID- 14586348
TI  - Fetal transcerebellar diameter nomogram in singleton gestations with special
      emphasis in the third trimester: a comparison with previously published
      nomograms.
AB  - OBJECTIVE: This study was undertaken to construct an institution-specific
      transverse cerebellar (transcerebellar) diameter nomogram with special emphasis
      in the third trimester and to compare its ability to predict gestational age with
      previously published nomograms. STUDY DESIGN: A cross-sectional nomogram was
      constructed using transcerebellar diameter measurements in 24,026 well-dated
      singleton fetuses by using linear regression models. Third-trimester measurements
      from 2,010 fetuses were included. The performance of previously established
      transcerebellar diameter nomograms for predicting gestational age was assessed in
      our population to determine comparability between nomograms. RESULTS:
      Interobserver and intraobserver variabilities in the second and third trimesters
      were 3.1% to 3.7% and 3.4% to 3.8%, respectively. Between 14 and 27 weeks'
      gestation, there were no clinically important differences between our nomogram
      and those previously published in terms of the predicted gestational age.
      However, predicted gestational age in the third trimester was considerably
      different by using our nomogram by 1 to 2 weeks from 28 to 30 weeks and by 4 to 6
      weeks after 32 weeks. CONCLUSION: Transcerebellar measurements had a similar
      relationship with gestational age across previously published nomograms before 28
      weeks. However, clinically significant differences in predicting gestational age
      appear later, especially after 32 weeks. These findings suggest that this new
      nomogram may be particularly useful for accurate dating of pregnancies in the
      third trimester.

PMID- 14586350
TI  - A prospective randomized controlled trial that compared misoprostol, Foley
      catheter, and combination misoprostol-Foley catheter for labor induction.
AB  - OBJECTIVE: The purpose of this study was to determine the efficacy of combination
      intravaginal misoprostol and intracervical Foley catheter for prelabor cervical
      ripening. STUDY DESIGN: A prospective, randomized controlled trial was conducted.
      Women who were undergoing labor induction, with a singleton gestation >or=28
      weeks and an unfavorable cervix (Bishop score <or=6), were assigned to one of
      three groups: (1) intravaginal misoprostol 25 mug every 3 hours, (2)
      intracervical 16F Foley catheter, or (3) combination misoprostol-Foley catheter.
      RESULTS: Among 146 patients, 49 patients were assigned to misoprostol, 54
      patients were assigned to Foley catheter, and 43 patients were assigned to
      combination therapy. There was no difference in vaginal delivery rates
      (misoprostol, 63.3%; Foley, 57.4%; combination, 58.1%; P=.81). There were also no
      statistically significant differences in the interval between induction to active
      phase, active phase to delivery, or induction to delivery among the three groups.
      CONCLUSION: Intravaginal misoprostol and intracervical Foley catheter are
      comparable for preinduction cervical ripening. The combination of the two methods
      did not provide additional efficacy.

PMID- 14586349
TI  - The MisoPROM study: a multicenter randomized comparison of oral misoprostol and
      oxytocin for premature rupture of membranes at term.
AB  - OBJECTIVE: This study was undertaken to determine whether induction of labor with
      oral misoprostol will result in fewer cesarean deliveries than intravenous
      oxytocin in nulliparous women with premature rupture of membranes at term. STUDY
      DESIGN: Three hundred five women at 10 centers were randomly assigned to receive
      oral misoprostol, 100 microg every 6 hours to a maximum of two doses or
      intravenous oxytocin. The primary outcome measure was cesarean deliveries.
      Secondary outcomes were time from induction to vaginal delivery and measures of
      maternal and neonatal safety. RESULTS: The study was stopped prematurely because
      of recruitment difficulties. We present the results for the 305 enrolled women.
      There was no difference in the proportion of women who underwent cesarean
      delivery (20.1% in the misoprostol group, 19.9% in the oxytocin group). The time
      interval from induction to vaginal delivery was also similar (11.9 hours for the
      misoprostol group, and 11.8 hours for the oxytocin group). Maternal and neonatal
      safety outcomes were similar for the two treatments. More infants born to women
      in the misoprostol group received intravenous antibiotics in the neonatal period
      (16.4% vs 6.9%, P=.01), although there were no differences in chorioamnionitis or
      in proven neonatal infections. Women receiving misoprostol were less likely to
      have postpartum hemorrhage than those receiving oxytocin (1.9% vs 6.2%, P=.05).
      CONCLUSION: Oral misoprostol does not offer any advantage in time from induction
      to vaginal delivery or risk of cesarean section.

PMID- 14586351
TI  - The descent curve of the grand multiparous woman.
AB  - OBJECTIVE: The purpose of this study was to compare the descent curves and second
      stage length among grand multiparous, nulliparous, and lower parity multiparous
      women. STUDY DESIGN: Retrospective cohorts of spontaneously laboring, vertex
      presenting, term, grand multiparous women (parity >or=5) from two medical centers
      over 5.5 years were matched randomly to nulliparous women and lower parity
      multiparous women controlled for age, hospital, and year of delivery. Descent
      curves were modeled from serial cervical examination data by the estimation of
      the probability of a given station occurring at a given time before delivery with
      the use of ordinal logistic regression. Curves were compared by Wald tests and
      adjusted for possible confounders. Second-stage lengths were compared by a Cox
      proportional hazards model. A probability value of <.05 was considered
      significant. RESULTS: Grand multiparous women and lower parity multiparous women
      maintain a high station up to 1.5 hour before delivery and then rapidly
      transition to delivery. Nulliparous women transition to lower stations at a more
      gradual rate throughout the first and second stages. Descent curves differ among
      parity groups, with grand multiparous women maintaining a higher station for a
      longer time compared with either lower parity multiparous women or nulliparous
      women (P<.001). Once full dilation is reached, the median length of the second
      stage is 0.75, 0.85, and 1.75 hours for grand multiparous women, lower parity
      multiparous women, and nulliparous women, respectively (hazard ratios were 0.39
      for nulliparous women vs grand multiparous women and 0.9 for lower parity
      multiparous women vs grand multiparous women). CONCLUSIONS: Compared with lower
      parity multiparous women or nulliparous women, grand multiparous women maintain a
      higher station for a longer time before delivery but transition rapidly to
      delivery once full dilation is reached.

PMID- 14586352
TI  - Uterine rupture: risk factors and pregnancy outcome.
AB  - OBJECTIVES: This study aimed at determining risk factors and pregnancy outcome in
      women with uterine rupture. STUDY DESIGN: We conducted a population-based study,
      comparing all singleton deliveries with and without uterine rupture between 1988
      and 1999. RESULTS: Uterus rupture occurred in 0.035% (n=42) of all deliveries
      included in the study (n=117,685). Independent risk factors for uterine rupture
      in a multivariable analysis were as follows: previous cesarean section (odds
      ratio [OR]=6.0, 95% CI 3.2-11.4), malpresentation (OR=5.4, 95% CI 2.7-10.5), and
      dystocia during the second stage of labor (OR=13.7, 95% CI 6.4-29.3). Women with
      uterine rupture had more episodes of postpartum hemorrhage (50.0% vs 0.4%,
      P<.01), received more packed cell transfusions (54.8% vs 1.5%, P<.01), and
      required more hysterectomies (26.2% vs 0.04%, P<.01). Newborn infants delivered
      after uterine rupture were more frequently graded Apgar scores lower than 5 at 5
      minutes and had higher rates of perinatal mortality when compared with those
      without rupture (10.3% vs 0.3%, P<.01; 19.0% vs 1.4%, P<.01, respectively).
      CONCLUSION: Uterine rupture, associated with previous cesarean section,
      malpresentation, and second-stage dystocia, is a major risk factor for maternal
      morbidity and neonatal mortality. Thus, a repeated cesarean delivery should be
      considered among parturients with a previous uterine scar, whose labor failed to
      progress.

PMID- 14586353
TI  - What is the best measure of maternal complications of term pregnancy: ongoing
      pregnancies or pregnancies delivered?
AB  - OBJECTIVE: The purpose of this study was to determine whether rates of
      hypertensive disorders of pregnancy increase beyond 37 weeks of gestation and to
      address how best to analyze these rates. STUDY DESIGN: This was a retrospective
      cohort study of all women delivered beyond 37 weeks' gestational age from 1995 to
      1999 at all Kaiser Permanente Medical Care Program delivery hospitals in Northern
      California. Rates of gestational hypertension, preeclampsia, and eclampsia were
      calculated by use of both pregnancy delivered (PD) and ongoing pregnancy (OP) as
      the denominator. Bivariate and multivariate analyses were conducted with use of
      P<.05 to indicate statistical significance. RESULTS: Among the 135,560 women in
      this cohort, the rates of gestational hypertension, preeclampsia, and eclampsia
      were the same or decreased from 37 to 43 weeks' gestation using PD, but all three
      increased when calculated according to OP (P<.01). CONCLUSION: We found that
      among complications of pregnancy that are diagnosed ante partum, use of a
      different denominator led to contradictory conclusions. When hypertensive
      disorders of pregnancy are analyzed, ongoing pregnancies should be used as the
      denominator.

PMID- 14586354
TI  - The association between respiratory distress and nonpulmonary morbidity at 34 to
      36 weeks' gestation.
AB  - OBJECTIVE: The study was undertaken to determine whether respiratory distress
      syndrome (RDS) is associated with an increased risk of nonpulmonary morbidity in
      neonates born between 34 to 36 weeks' gestation. STUDY DESIGN: We performed a
      matched case-control study of 75 infants with (cases) and 75 without (controls)
      RDS, delivered between 34 and 36 weeks' gestation. Infants with RDS and no other
      causes for respiratory failure (anomalies, hydrops, asphyxia) were included.
      Controls were matched for gestational age at birth, year of care, gender,
      plurality, and race. Inpatient records were reviewed for the incidence of
      nonpulmonary morbidities before discharge. McNemar test and conditional logistic
      regression were used to evaluate differences between cases and controls. RESULTS:
      Our study cohort was 69% male, 48% white, 33% African American, and 19% Hispanic.
      Cases had longer hospital (11 vs 7days) and neonatal intensive care unit stays
      (10 vs 7 days), and more frequent apnea-bradycardia (30% vs 5%), pneumonia (12%
      vs 1%), and suspected sepsis diagnoses (27% vs 3%), P <or=.008 for each.
      Antibiotic use (96% vs 45%), transfusion (20% vs 0%), phototherapy (57% vs 29%),
      and hyperalimentation (57% vs 4%) were more common in the RDS group, P <or=.002
      for each. Other major morbidities (intraventricular hemorrhage, patent ductus
      arteriosus, necrotizing enterocolitis, bronchopulmonary dysplasia) were uncommon
      in cases and controls. Similar results were obtained when controlling for mode of
      delivery and antenatal steroid use. CONCLUSION: RDS at 34 to 36 weeks is
      associated with increased morbidity and neonatal interventions. In the absence of
      RDS, major morbidity is uncommon.

PMID- 14586355
TI  - Ethnic differences in birth weight by gestational age: at least a partial
      explanation for the Hispanic epidemiologic paradox?
AB  - OBJECTIVE: The purpose of this study was to evaluate ethnic differences in low
      birth weight and gestational age-dependent birth weight. STUDY DESIGN: A
      retrospective cohort study of 47,669 newborn infants was conducted with the use
      of the perinatal database of the Memorial Health Care System. Logistic regression
      was used to estimate the odds ratio for low birth weight by ethnic group, which
      took into account gestational age at delivery. Multiple linear regression models
      were then developed to predict ethnic differences in birth weight by gestational
      age. RESULTS: When compared with white women, the adjusted odds ratio for low
      birth weight in of Mexican origin women (1.16; 95% CI, 1.02-1.32) was
      substantially lower than that of African American women (2.21; 95% CI, 1.87
      2.60). An analysis of birth weight by gestational age suggested that African
      American neonates were intrinsically smaller than Hispanic neonates (difference,
      4.22%). CONCLUSION: At least some of the differences in low birth weight that are
      noted among ethnic minorities may be attributable to ethnic differences in birth
      weight by gestational age.

PMID- 14586356
TI  - Failure of physiologic transformation of the spiral arteries in patients with
      preterm labor and intact membranes.
AB  - OBJECTIVE: The purpose of this study was to determine whether abnormal
      placentation (defined as the failure of physiologic transformation of spiral
      arteries) is present in patients with preterm labor and intact membranes who
      delivered a preterm neonate. STUDY DESIGN: A cross-sectional study was conducted
      to examine the histopathologic findings in the placental bed and placenta of
      patients with preterm labor and intact membranes (n=27), preeclampsia (n=43), and
      healthy pregnant women at term (n=103). Immunohistochemistry studies with
      cytokeratin 7 and periodic acid-Schiff were used to detect trophoblast and
      fibrinoid, respectively, and diagnose the failure of physiologic transformation
      of the spiral arteries. RESULTS: The mean percentage of spiral arteries with
      failure of physiologic transformation in the myometrium was significantly higher
      in patients with preterm labor and preeclampsia than in normal pregnant women at
      term (P=.0004 and P<.0001, respectively). Similar findings were observed in the
      decidual segment of spiral arteries within the placental bed (P=.001 and
      P<.0001). In contrast, the mean percentage of the spiral arteries with failure of
      physiologic transformation in the decidua of the basal plate was not
      significantly different between patients with preterm labor and normal pregnant
      women (P=.17). CONCLUSION: Failure of physiologic transformation of the spiral
      arteries in the myometrial and decidual segments of the placental bed is frequent
      in patients with preterm labor and intact membranes.

PMID- 14586357
TI  - Sublingual nitroglycerin versus placebo as a tocolytic for external cephalic
      version: a randomized controlled trial in parous women.
AB  - OBJECTIVE: The purpose of this study was to evaluate the efficacy of sublingual
      nitroglycerin as a tocolytic agent for external cephalic version in parous women.
      STUDY DESIGN: A double-blinded randomized controlled trial was performed.
      Patients with parity of >or=1 at 36 to 40 weeks of gestation who were eligible
      for external cephalic version were included. Patients were randomized to receive
      either two sublingual sprays of 400 mug of nitroglycerin or two sprays of placebo
      3 minutes before the trial of external cephalic version. Rates of successful
      external cephalic version and side effects were compared between groups. RESULTS:
      Of 99 patients in the study, 50 patients received sublingual nitroglycerin, and
      49 patients received placebo. There were no differences in maternal age,
      gestational age, estimated fetal weight, amniotic fluid index, and placental
      location between the two groups. The success rate of external cephalic version
      was 48% in the nitroglycerin group compared with 63% in the placebo group
      (P=.13). There was a higher incidence of headaches in the nitroglycerin group
      (42% vs 4%, P<.001). CONCLUSION: Sublingual nitroglycerin was associated with a
      higher rate of headache and did not improve the rate of successful external
      cephalic version.

PMID- 14586358
TI  - Transvaginal ultrasound-assisted gynecologic surgery: evaluation of a new device
      to improve safety of intrauterine surgery.
AB  - OBJECTIVE: The purpose of this study was to evaluate a new device that couples
      any standard transvaginal ultrasound transducer to a special tenaculum by means
      of a specially designed adaptor that enables real-time ultrasound imaging and
      guidance of intrauterine surgical procedures. STUDY DESIGN: Forty-five patients
      who underwent intrauterine surgical interventions were evaluated. Forty of these
      patients had pregnancy terminations. Three patients had curettage for early
      pregnancy complications. One patient had a polyp removed, and one patient
      underwent hysteroscopic submucous myomectomy. Five attending physicians performed
      26 procedures. Four residents in training performed 19 procedures. All operators
      were instructed in the assembly and use of the device before their first
      procedure. Evaluation of the device was done by means of a detailed
      questionnaire. RESULTS: The procedures were completed successfully and without
      complications. The time that was involved for the various components of the
      surgical procedures was recorded; 83% to 90% of the time the operators felt that
      the technique increased safety and accuracy for the parameters that were
      evaluated. They required fewer intrauterine instrument manipulations; in 85% of
      the cases, they could detect the exact end point of the procedure more
      accurately. In 12% of cases, the operators felt that the device interfered with
      the performance of the procedure. CONCLUSIONS: The transvaginal ultrasound
      assisted gynecological surgery system provided high-resolution images of the
      cervical canal and the uterine cavity during all stages of the procedure and
      provided improved indication of the procedure's end point. The increased safety
      and accuracy that was reported by most users was encouraging. The transvaginal
      ultrasound-assisted gynecologic surgery system appears to provide an enhanced
      alternative to transabdominal ultrasound guidance for intrauterine surgical
      procedures.

PMID- 14586359
TI  - Endocrine assessment of relative reproductive age in normal eumenorrheic younger
      and older women across multiple cycles.
AB  - OBJECTIVE: The aim of this study was to better characterize the ranges and
      intercycle variability for day 3 follicle-stimulating hormone, estradiol, and
      inhibin B levels in normal eumenorrheic women. STUDY DESIGN: Healthy eumenorrheic
      volunteers were recruited, of whom 27 women were 20 to 25 years old (peak
      reproductive age) and 36 women were 40 to 45 years old (study population). Blood
      samples were obtained on day 3 of two consecutive menstrual cycles. In some
      women, an additional blood sample on day 3 was obtained within 1 year. RESULTS:
      In normal women aged 20 to 25 years versus women aged 40 to 45 years, the day 3
      follicle-stimulating hormone geometric mean is 5.6 IU/L (95% CI, 3.3-9.5 IU/L)
      versus 9.6 IU/L (95% CI, 3.8-23.8 IU/L), the day 3 estradiol geometric mean is
      44.0 pg/mL (95% CI, 20.4-95.0 pg/mL) versus 52.4 pg/mL (95% CI, 22.4-122.8
      pg/mL), and the day 3 inhibin B geometric mean is 100.4 pg/mL (95% CI, 51.7-195.0
      pg/mL) versus 52.4 pg/mL (95% CI, 9.5-289.3 pg/mL). Furthermore, 22% of women in
      the older age group have a normal day 3 follicle-stimulating hormone and
      estradiol level in one cycle but an elevated value in a consecutive cycle
      (P=.008). CONCLUSION: In women of peak reproductive age, the upper limit of day 3
      follicle-stimulating hormone and estradiol levels are 9.5 IU/L and 95.0 pg/mL,
      respectively, and the lower limit of day 3 inhibin B level is 51.7 pg/mL. If the
      initial day 3 follicle-stimulating hormone and estradiol levels in an older woman
      are normal, then a second measurement in a subsequent cycle should be obtained
      before counseling this woman regarding her reproductive potential.

PMID- 14586360
TI  - Human progesterone receptor polymorphisms and implantation failure during in
      vitro fertilization.
AB  - OBJECTIVE: Polymorphic variants of the human progesterone receptor gene have been
      described, but their potential influence on in vitro fertilization outcome have
      not been studied. STUDY DESIGN: DNA was available from 317 women (cases) who had
      >or=2 embryo transfers without a clinical pregnancy and from 288 women (control
      subjects) who became pregnant after 1 in vitro fertilization attempt. With
      protocols that were specific for H770H (C/T genotype) and +331G/A polymorphism,
      amplification of polymorphism fragments, digestion with restriction enzymes, and
      gel visualization were performed. RESULTS: Allele frequencies for the 2 variants
      were 15.5% for H770H T and 4.1% for +331A in cases and 17.9% and 3.6% in control
      subjects, respectively. Both polymorphisms were rare among non-white subjects.
      Possession of a H770H T allele was associated with a decreased risk for
      implantation failure, which was nonsignificant overall but significant in women
      aged <35 years (adjusted relative risk, 0.52 [95% CI, 0.28, 0.97]). Possession of
      a +331A allele was associated with an increased risk of implantation failure,
      which was nonsignificant overall but significant in women who weighed <135 pounds
      (adjusted relative risk, 3.85 [95% CI, 1.20, 12.30]). The +331G/A polymorphism
      tended to increase the risk for implantation failure in women with an H770H C/C
      genotype, but not in women with a C/T or TT genotype (P=.09). Among white women
      who were H770H C/C, there was a significant trend (P=.03) in the proportion of
      +331G/A carriers as the number of implantation failures increased, from 8.6% of
      women with 0 failed attempts to 40% among women with >or=5 failed attempts.
      CONCLUSION: Although human progesterone receptor polymorphisms do not clearly
      affect the risk for implantation failure in most women who undergo in vitro
      fertilization, the likelihood that a woman carries the +331G/A human progesterone
      receptor polymorphism increases with the number of failed attempts at
      implantation.

PMID- 14586361
TI  - Sexual partners and use of emergency contraception.
AB  - OBJECTIVE: This study investigates the role of male sexual partners and
      relationships in determining whether women seek emergency contraception (EC) when
      needed. STUDY DESIGN: Data on EC use from a clinic-based sample of sexually
      active women, aged 15 to 30 years, in the San Francisco Bay area (n=497) were
      analyzed with multivariate logistic regression analysis. RESULTS: Results show
      that factors measuring power dynamics, such as male dominant decision making
      (odds ratio [OR]=4.1, P=.035) and pressure for sex (OR=2.7, P=.006), as well as a
      strong desire to avoid pregnancy on the part of the male partner (OR=4.2, P
      <or=.001), have a significant association with the use of EC. However,
      relationship factors known to be associated with use of other contraceptive
      methods, such as communication, satisfaction, and commitment, show no association
      with EC use. CONCLUSION: Factors predicting EC use, including male partner and
      relationship factors, may not always be evident to a clinician, so it is
      important to include EC as part of routine counseling.

PMID- 14586362
TI  - Urethral pressure changes in response to squeeze: a population-based study in
      healthy and incontinent 53- to 63-year-old women.
AB  - OBJECTIVE: The purpose of this study was to investigate the urethral pressure
      pattern during short squeezes in incontinent and healthy women before and after
      pelvic floor exercise and to correlate the findings with vaginal measurements.
      STUDY DESIGN: Sixty women with urinary incontinence and 28 healthy control
      subjects all aged 53 to 63 years were subject to urethral pressure measurements
      and vaginal palpation, pressure and surface electromyography measurements.
      Measurements were repeated after 4 months of pelvic floor exercise in the
      incontinent group. RESULTS: The appearance of the urethral pressure curve during
      a squeeze on a semiquantitative scale from 0 to 4, in the healthy group, was
      2.2+/-0.3 and, in the incontinent group, was 1.5+/-0.2 (P<.0 5), rising to 2.2+/
      0.2 after pelvic floor exercise (P<.01). The semiquantitative grading correlated
      with vaginal measurements. CONCLUSION: The increase of the urethral pressure in
      response to short squeeze is reduced significantly in incontinent women compared
      with healthy women of the same age and parity. A normalization was seen after
      pelvic floor exercise in the incontinent group.

PMID- 14586363
TI  - Efficacy of desmopressin (Minirin) in the treatment of nocturia: a double-blind
      placebo-controlled study in women.
AB  - OBJECTIVE: The purpose of this study was to investigate the efficacy and safety
      of oral desmopressin in the treatment of nocturia in women. STUDY DESIGN: Women
      aged 18 years or older with nocturia (>or=2 voids per night with a nocturia index
      score >1) received desmopressin (0.1 mg, 0.2 mg, or 0.4 mg) during a 3-week dose
      titration period. After a 1-week washout period, patients who responded in this
      period received desmopressin or placebo in a double-blind fashion for 3 weeks.
      RESULTS: In double-blind phase, 144 patients were randomly assigned to groups
      (desmopressin, n=72; placebo, n=72). For desmopressin, 33 (46%) patients had a
      50% or greater reduction in nocturnal voids against baseline levels compared with
      5 (7%) patients receiving placebo (P<.0001). The mean number of nocturnal voids,
      duration of sleep until the first nocturnal void, nocturnal diuresis, and ratios
      of nocturnal per 24 hours and nocturnal per daytime urine volumes changed
      significantly in favor of desmopressin versus placebo (P<.0001). In the dose
      titration phase headache (22%), nausea (8%), and hyponatremia (6%) were reported.
      Two deaths occurred, although neither could be directly associated with the study
      drug. CONCLUSION: Oral desmopressin is an effective and well-tolerated treatment
      for nocturia in women.

PMID- 14586364
TI  - Pelvic floor nerve conduction studies: establishing clinically relevant normative
      data.
AB  - OBJECTIVE: The purpose of this study was to establish data for normative
      distributions for pudendal and perineal nerve compound muscle action potential
      data in healthy women across a wide age range and varied history of vaginal
      deliveries. STUDY DESIGN: We studied 42 continent women, aged 20 to 67 years,
      including 29% nulliparous women with a disposable St. Mark's electrode to
      stimulate the pudendal nerve at the ischial spine by a transvaginal approach. The
      pudendal terminal motor latency and amplitude were detected with the use of
      surface patch electrodes overlying the external anal sphincter; the perineal
      responses were measured with the use of a surface ring electrode at the proximal
      urethra. RESULTS: None of the data were distributed normally and required the use
      of negative inverse and cube root transformations to create a normal
      distribution. Clinical correlations were found with advancing age and vaginal
      delivery. CONCLUSION: The collection of these data allows for the definition of
      normal limits and begins the study of clinically important variables on test
      results and clinical outcomes.

PMID- 14586365
TI  - Ovarian cancer: changes in patterns at diagnosis and relative survival over the
      last three decades.
AB  - OBJECTIVE: The purpose of this study was to examine patterns of diagnosis and
      relative survival in women who had a diagnosis of primary invasive epithelial
      ovarian cancer (EOC) from 1973 to 1997, with follow-up through the end of 1999.
      STUDY DESIGN: From the population-based Surveillance, Epidemiology and End
      Results (SEER) Program, 32,845 women diagnosed between 1973 and 1997 were used
      for analysis. The study population was divided in three cohorts based on year of
      diagnosis and the cohorts were compared with respect to variables of interest by
      using chi(2) tests and relative survival analysis by the life table method.
      RESULTS: There was an increase in the proportions of minorities diagnosed with
      EOC, of women 60 years or older at diagnosis, and of women undergoing surgery
      over time. Survival continuously improved over time, although older patients (60
      years or older) and African Americans continued to have the poorest survival.
      CONCLUSION: Over time, relative survival of women who had primary invasive EOC
      diagnosed improved.

PMID- 14586366
TI  - Cancer associated with obstetric delivery: results of linkage with the California
      cancer registry.
AB  - OBJECTIVE: This study provides revised population-based measurements for the
      occurrence rates of cancer associated with obstetric delivery and examines
      perinatal and cancer-related outcomes within the group of women with 4,846,505
      obstetric deliveries in California, inclusive of the years 1991 through 1999.
      STUDY DESIGN: This observational study used a population-based retrospective
      review of cases identified as a result of computer linkage of maternal/neonatal
      hospital discharge and birth/death records with case files in the California
      Cancer Registry (CCR). The effect of timing of cancer diagnosis on clinical
      outcomes was studied by dividing the cases into three groups as follows:
      "prenatal" for cancer diagnosis within 9 months before delivery, "at delivery"
      for cancer diagnosis during delivery hospitalization, and "post partum" for
      cancer diagnosis within 12 months after delivery. Computerized records for
      4,846,505 obstetric patients and 4,906,920 newborn infants comprising the linked
      vital statistics birth/patient discharge database (VS/PDD) were used to identity
      match cases within the CCR case files. Cases of malignant disease were
      categorized into 22 anatomic or histologic subgroups. Perinatal clinical outcomes
      including preterm delivery, prolonged neonatal hospital stay, stillbirth,
      neonatal death, frequency of first trimester prenatal care, and cesarean delivery
      were analyzed by use of International Classification of Diseases, 9th Revision,
      Clinical Modification codes from the VS/PDD. Clinical cancer outcomes including
      cancer stage and vital status on follow-up were drawn from CCR records.
      Statistical comparisons for trends were performed with the Cochran-Armitage test,
      outcomes comparisons with the Fisher exact test, and survival comparisons were
      performed with the Cox proportional hazard model. RESULTS: Among 4,846,505
      obstetric deliveries, 4,539 cases of invasive malignancy were identified for an
      observed occurrence rate of 0.94 per 1000 births. Sixty-four percent of the cases
      occurred post partum; cancers of the breast, thyroid, cervix, along with
      malignant melanoma, and Hodgkin's disease accounted for 64% of the cases. The
      timing of cancer diagnosis affected clinical outcomes: for all cancer cases as a
      group, the most favorable perinatal and cancer outcomes occurred in women whose
      cancer diagnosis was made 6 to 9 months before delivery (6% of cases). The most
      unfavorable perinatal and cancer outcomes were associated with cancer diagnosis
      made 0 to 3 months before delivery (14% of cases). For women whose cancer was
      diagnosed post partum, perinatal outcomes were minimally affected by the presumed
      existence of occult cancer at the time of obstetric delivery. CONCLUSION: The use
      of computer-linkage to the CCR files enhanced identification of cases of maternal
      malignancy associated with obstetric delivery. Cancer diagnosis was associated
      with approximately 1 in 1000 deliveries. Most cases were diagnosed after delivery
      and were comprised predominantly of cancers of the breast, thyroid, cervix,
      malignant melanoma, and Hodgkin's disease. A small group of women (approximately
      1 per 5000 deliveries) are seen within a few months before delivery or at
      delivery with malignant disease, many of whom have rapidly progressing disease
      and may require high-risk perinatal and oncology services.

PMID- 14586367
TI  - Patient distress and satisfaction with optical spectroscopy in cervical dysplasia
      detection.
AB  - OBJECTIVE: The aim of this investigation was to evaluate the impact of optical
      spectroscopy, a new approach for the detection of cervical dysplasia, on patient
      well-being and satisfaction. STUDY DESIGN: Patient distress and satisfaction with
      optical spectroscopy compared with the Papanicolaou test and colposcopically
      directed biopsy were measured in a volunteer sample of 314 women with no history
      of abnormal Papanicolaou test findings. RESULTS: Participants reported
      significantly less pain and anxiety (P<.001) during optical spectroscopy than
      during the Papanicolaou test or colposcopically directed biopsy. Generally,
      participants found spectroscopy equal to the Papanicolaou test and to biopsy on a
      variety of questions that measured satisfaction. There were statistically
      significant differences between spectroscopy and the Papanicolaou test or biopsy
      on issues such as the discomfort and fear caused by the test, the amount of time
      taken, the room lighting, and perceptions of accuracy. CONCLUSION: That patients
      reported less distress during spectroscopy than during a Papanicolaou test,
      colposcopy, or biopsy suggests the possibility of improved adherence to cervical
      cancer screening and follow-up in settings in which it is used.

PMID- 14586368
TI  - Labor and delivery factors in brain damage, disabling cerebral palsy, and
      neonatal death in low-birth-weight infants.
AB  - OBJECTIVE: We assessed the relationships between active labor and neonatal death,
      neonatal brain damage, and disabling cerebral palsy in low-birth-weight infants.
      STUDY DESIGN: A population-based cohort of 961 infants with birth weights of 580
      to 2000 g and gestational ages >or=26 completed weeks. Neonatal brain damage was
      assessed by ultrasound scanning in the first weeks of life; disabling cerebral
      palsy was assessed at 2 years of age (corrected for gestational age). RESULTS:
      After being controlled for possible confounders, active labor was associated
      significantly with an increased risk of parenchymal echodensities/lucencies
      and/or ventricular enlargement (odds ratio, 2.3; 95% CI, 1.2-4.5) but not with
      germinal matrix/intraventricular hemorrhage (odds ratio, 1.3; 95% CI, 0.8-2.1),
      neonatal death (odds ratio, 1.8; 95% CI, 0.8-4.0), or disabling cerebral palsy
      (odds ratio, 1.6; 95% CI, 0.7-3.7). In vertex presentations only, active labor
      was associated with a nearly 4-fold increase in risk of neonatal death (odds
      ratio, 3.8; 95% CI, 1.3-10.9). In nonvertex presentations only, active labor was
      associated strongly with parenchymal echodensities/lucencies and/or ventricular
      enlargement (odds ratio, 4.3; 95% CI, 1.2-15.6) and disabling cerebral palsy
      (odds ratio, 8.2; 95% CI, 1.4-49.9). CONCLUSION: The only adverse outcome that
      was associated consistently with active labor was parenchymal
      echodensities/lucencies and/or ventricular enlargement. Fetal presentation
      modified the relationships between active labor and adverse outcomes. Delivery
      mode (whether vaginal or cesarean delivery) was not associated with any of the
      outcomes that were evaluated.

PMID- 14586369
TI  - Elevated vaginal pH and neutrophils are associated strongly with early
      spontaneous preterm birth.
AB  - OBJECTIVE: The purpose of this study was to determine the association of vaginal
      pH>or=5.0 and vaginal neutrophils >5 per oil-field with early preterm birth.
      Study design This is a secondary analysis of the vaginal infections and
      prematurity cohort comprised of 13,917 women at 23 and 26 weeks of gestation. All
      women were tested for sexually transmitted infections and vaginal pH. Gram
      stained smears were used for the detection of neutrophils. RESULTS: There were
      5751 women (41.3%) with neutrophils >5 per oil-field and 2500 women (18.0%) with
      pH>or=5.0. Both elevated pH and neutrophils were present in 1149 women (8.3%).
      Neutrophils and pH were each significantly associated with spontaneous preterm
      birth, and the point estimate of the strength of that association increased as
      the gestational age at delivery decreased. CONCLUSION: Elevated vaginal pH and
      neutrophils are associated most strongly with the earliest preterm births.

PMID- 14586370
TI  - Vitamin and homocysteine status of mothers and infants and the risk of
      nonsyndromic orofacial clefts.
AB  - OBJECTIVE: This study was undertaken to investigate the involvement of maternal
      and infant B vitamins and homocysteine as risk factors for orofacial clefting.
      STUDY DESIGN: Venous blood samples were taken from 96 infants with nonsyndromic
      orofacial clefts and 88 infants without a congenital malformation and from their
      mothers at approximately 14 months after the index pregnancy. Red blood cell and
      serum folate, serum vitamin B(12), whole blood vitamin B(6) as pyridoxal-5'
      phosphate (PLP), and plasma homocysteine concentrations were measured. RESULTS: A
      vitamin B(12) concentration of 185 pmol/L or less and a PLP concentration of 44
      nmol/L or less in mothers increased the risk of having a child with an orofacial
      cleft (odds ratio [OR]=3.1; 95% CI: 1.3-7.4, OR=2.9; 95% CI: 1.2-7.1,
      respectively). Infants with orofacial clefts had a 15% lower serum folate
      concentration compared with controls (P=.06). CONCLUSION: A low vitamin B(12) and
      PLP concentration in mothers increased the risk of orofacial clefts in the
      offspring. A possible role of the infant's folate status is suggested.

PMID- 14586371
TI  - Monocyte chemotactic protein-1 in cervical and amniotic fluid: relationship to
      microbial invasion of the amniotic cavity, intra-amniotic inflammation, and
      preterm delivery.
AB  - OBJECTIVE: The purpose of this study was to evaluate the role of monocyte
      chemotactic protein-1 in cervical and amniotic fluid in women in preterm labor
      and with preterm premature rupture of membranes. STUDY DESIGN: Women with
      singleton pregnancies (<or=34 weeks) in preterm labor (n=75 women), with preterm
      premature rupture of membranes (n=47 women), and at term (n=45 women) who were
      undergoing elective cesarean delivery were included. Cervical and amniotic fluid
      were sampled. RESULTS: Monocyte chemotactic protein-1 in cervical and amniotic
      fluid was higher in women in preterm labor than in women at term. Cervical
      monocyte chemotactic protein-1 in women in preterm labor was associated with
      microbial invasion of the amniotic cavity, intra-amniotic inflammation, delivery
      within 7 days, and at <or=34 weeks. Amniotic monocyte chemotactic protein-1
      correlated to microbial invasion of the amniotic cavity in women with preterm
      premature rupture of membranes, intra-amniotic inflammation in preterm labor,
      preterm premature rupture of membranes, delivery within 7 days, and delivery at
      <or=34 weeks in women in preterm labor. CONCLUSION: Monocyte chemotactic protein
      1 in cervical and amniotic fluid levels are elevated in preterm labor and preterm
      premature rupture of membranes and correlate to intra-amniotic
      infection/inflammation.

PMID- 14586372
TI  - Prediction of brachial plexus stretching during shoulder dystocia using a
      computer simulation model.
AB  - OBJECTIVE: The purpose was to study the impact of maternal endogenous and
      clinician-applied exogenous delivery forces on brachial plexus stretching during
      a shoulder dystocia event. STUDY DESIGN: A computer software crash dummy model
      (MADYMO, version 5.4, TNO Automotive, Delft, The Netherlands) was modified on the
      basis of established maternal pelvis and fetal anatomic specifications. The
      brachial plexus was modeled as a spring, with mechanical properties that were
      based on previously reported experimental data. Increasing amounts of endogenous
      or exogenous loading forces were applied until delivery of the anterior fetal
      shoulder occurred. Brachial plexus deformation was assessed as percent stretch in
      the nerve (Change in length/Original length x 100). RESULTS: With lithotomy
      positioning, both maternal endogenous and clinician-applied exogenous delivery
      forces were associated with brachial plexus stretching (15.7% vs 14.0%,
      respectively). McRoberts positioning reduced needed loading forces for delivery
      and resulted in 53% less brachial plexus stretch (6.6%). Downward lateral
      displacement of the fetal head was associated with a 30% increase in brachial
      plexus stretch (18.2%) compared with axial positioning of the head (14.0%).
      CONCLUSION: Brachial plexus stretch varied as a result of the load required for
      delivery, the source of the applied force, pelvic orientation, and fetal head
      positioning. Maternally derived and clinician-applied delivery forces can both
      lead to brachial plexus deformation when shoulder dystocia is encountered. The
      McRoberts maneuver can reduce brachial plexus stretching. Management of fetal
      head position may also be important in reducing unnecessary brachial plexus
      stretch.

PMID- 14586374
TI  - The frequency and severity of placental findings in women with preeclampsia are
      gestational age dependent.
AB  - OBJECTIVE: The purpose of this study was to evaluate placental lesions found in
      women with preeclampsia compared with normotensive control subjects and to
      determine whether the presence of these lesions are related to gestational age at
      delivery. STUDY DESIGN: Placental disease of women with preeclampsia at 24 to 42
      weeks of gestation was compared with the placental disease of normotensive
      gestational age-matched control subjects. The placental lesions that were studied
      specifically included decidual arteriolopathy, thrombi in the fetal circulation,
      central infarction, intervillous thrombi, and hypermaturity of villi. Data
      analysis involved the chi(2) test, the Student t test, and logistic regression;
      odds ratios and CIs were estimated. RESULTS: Placentas from women with
      preeclampsia (n=158) and normotensive control subjects (n=156) were evaluated.
      Among women with preeclampsia, 67% had severe disease. Placental lesions were
      studied according to gestational age at delivery: <28, 28 to 32, 33 to 36, and
      >or=37 weeks of gestation. Of the placental lesions that were studied, decidual
      arteriolopathy (odds ratio, 23.8, 95% CI 10.0-57.0), hypermaturity of villi (odds
      ratio, 12.4; 95% CI 5.3-29.2), intervillous thrombi (odds ratio, 1.95;95% CI 1.0
      3.7), central infarction (odds ratio, 5.9; 95% CI 3.1-11.1), and thrombi in the
      fetal circulation (odds ratio, 2.8; 95% CI 1.2-6.6) were found to have
      significantly higher rates in the preeclamptic group. In contrast, the rate of
      chorioamnionitis was significantly lower in the preeclamptic group (odds ratio,
      0.2; 95% CI 0.1-0.4). The rates of abruptio placentae and meconium staining were
      not different between the two groups. Within the preeclamptic group, the rates of
      decidual arteriolopathy (P<.0001), central infarction (P=.0001), and
      hypermaturity of villi (P<.0001) were higher the earlier the gestational age at
      delivery. CONCLUSION: Placentas in women with preeclampsia have increased amounts
      of disease. The rate is increased with lower gestational ages at the time of
      delivery for women with preeclampsia.

PMID- 14586375
TI  - State laws regarding prenatal syphilis screening in the United States.
AB  - OBJECTIVE: The purpose of this study was to assess the frequency and pattern of
      state laws or regulations regarding prenatal syphilis serologic screening in the
      United States in 2001. STUDY DESIGN: We surveyed the United States for existing
      laws and regulations regarding serologic screening for syphilis during pregnancy.
      Testing was compared with 2000 state rates of syphilis in women and newborn
      infants, with states that had syphilis high morbidity areas, and with national
      2000 and 2010 objectives for rates of syphilis. RESULTS: Forty-six of the 50
      states (90%) and the District of Columbia have laws regarding antenatal syphilis
      screening. Thirty-four of the 46 statutes (76%) mandate one prenatal test,
      usually at the first prenatal visit or early in pregnancy. Twelve laws (26%)
      include third-trimester testing for all or high-risk women. The presence of high
      morbidity areas, incidence of early syphilis in women, and rates of congenital
      syphilis are associated with increasing frequency of legislated antepartum
      screening. CONCLUSION: Only 90% of states have statutes that require antepartum
      syphilis screening, and there is variation in the content of the statutes about
      the number and timing of tests. States with a heavy burden of infectious syphilis
      in women tend to require more prenatal testing.

PMID- 14586376
TI  - Placental villitis of unclear etiology during ovum donor in vitro fertilization
      pregnancy.
AB  - OBJECTIVE: Preliminary observations by a single pathologist at our institution
      revealed a 75% incidence of villitis of unexplained etiology in ovum donor in
      vitro fertilization pregnancies. Because the incidence of villitis of unexplained
      etiology in the general population is approximately 10%, we conducted a
      controlled study to compare the incidence of villitis of unexplained etiology in
      ovum donor in vitro fertilization pregnancies to that in in vitro fertilization
      pregnancies that do not use donated ova. STUDY DESIGN: Placental specimens of
      ovum donor in vitro fertilization pregnancies were matched randomly with
      pregnancies that resulted from both fresh and frozen/thawed native oocyte in
      vitro fertilization from March 5, 1995, to October 10, 2001, and examined in a
      blinded fashion by a single pathologist (D. J. R.) for villitis of unexplained
      cause. The incidence of villitis of unexplained etiology was analyzed in 27
      patients who underwent ovum donor in vitro fertilization versus 37 patients who
      underwent native oocyte in vitro fertilization. RESULTS: Villitis of unexplained
      cause occurred in 22.2% of ovum donor in vitro fertilization pregnancies, 10.8%
      of native oocyte in vitro fertilization pregnancies (fresh and frozen/thawed
      combined), and 14.3% of frozen/thawed cycles (P=.21). CONCLUSION: Although the
      incidence was not statistically different than in in vitro fertilization that
      used native maternal oocytes, there was a 2-fold increase in villitis of
      unexplained cause in the ovum donor in vitro fertilization placentas, which
      suggests that immune-related disorders may be increased in ovum donor
      pregnancies.

PMID- 14586377
TI  - The effects of pre-B-cell colony-enhancing factor on the human fetal membranes by
      microarray analysis.
AB  - OBJECTIVE: Our purpose was to show the effects of pre-B-cell colony-enhancing
      factor on the genes that are expressed by the human fetal membranes. STUDY
      DESIGN: Explants of fetal membranes (amnion, chorion, and decidua) from three
      term patients were treated with 100 ng/mL recombinant human pre-B-cell colony
      enhancing factor for 4 hours. RNAs were hybridized to gene chips that contained
      >18,000 known genes. One experiment was done in triplicate to assess replication.
      Data were analyzed to quantitate the signal intensities of each complementary DNA
      on the array. Confirmation of the results was carried out on tissues from nine
      other patients by the measurement of the proteins or quantitative real-time
      reverse transcriptase-polymerase chain reaction. RESULTS: Replication gave <92.6%
      identical results, which showed high method reproducibility. Pre-B-cell colony
      enhancing factor treatment caused a significant increase in 103 genes and
      decrease in 139 genes. Only 8 genes were up-regulated consistently and
      significantly in all three patients (three key inflammatory cytokines [tumor
      necrosis factor-alpha, interleukin-6, and interleukin-1beta], four important
      chemokines [macrophage inflammatory protein-1alpha, macrophage inflammatory
      protein-1beta, macrophage inflammatory protein-3alpha, and growth-related
      oncogene-gamma], and prostaglandin-endoperoxide synthase 2). These data were
      confirmed by the measurement in the media with the use of specific enzyme-linked
      immunosorbent assays for tumor necrosis factor-alpha, interleukin-6, and
      interleukin-1beta, macrophage inflammatory protein-1alpha, macrophage
      inflammatory protein-1beta, and macrophage inflammatory protein-3alpha and by
      quantitative real-time reverse transcriptase-polymerase chain reaction for growth
      related oncogene-gamma and prostaglandin-endoperoxide synthase 2. CONCLUSION: Pre
      B-cell colony-enhancing factor appears to be at the proximal end of the pathway
      to labor initiation and may link sterile distention-induced labor with that of
      infection-induced labor.

PMID- 14586379
TI  - The potential for probiotics to prevent bacterial vaginosis and preterm labor.
AB  - Infections of the urogenital tract in women represent a major burden on the
      quality of life of women and on the health care system of Canada and other
      countries. Complications arising from bacterial vaginosis (BV) include increased
      risk of sexually transmitted diseases including human immunodeficiency virus and
      elevated risk of preterm birth (PTB). Pharmaceutical interventions, such as
      antibiotics, have been suboptimally effective and have failed to reduce the
      incidence of PTB. The absence of lactobacilli in the vagina, a specific feature
      of BV, raises the question as to whether restoration of lactobacilli, by
      probiotic therapy, can restore the normal flora and improve the chances of having
      a healthy term pregnancy. The rationale for probiotic use in pregnant women is
      quite strong. Certain lactobacilli strains can safely colonize the vagina after
      oral and vaginal administration, displace and kill pathogens including
      Gardnerella vaginalis and Escherichia coli, and modulate the immune response to
      interfere with the inflammatory cascade that leads to PTB. Additional attributes
      of probiotics include their potential to degrade lipids and enhance cytokine
      levels, which promote embryo development. In a society that focuses on disease
      rather than health and drug therapy rather than natural preventive measures, it
      will take some effort to get remedies such as probiotics into mainstream care.
      Perhaps the escalating health care budgets and emergence of "superbugs" will
      provide the incentives to put in place clinical trials designed to evaluate how
      best to use the commensal organisms that, after all, make up more of our body
      than human cells, and without which none of us would survive.

PMID- 14586378
TI  - Smoking during pregnancy is associated with alterations in markers of endothelial
      function.
AB  - OBJECTIVE: Alterations in endothelial function may explain the reduced risk of
      preeclampsia that is associated with smoking. We hypothesized that markers of
      endothelial function increase over pregnancy but decrease with smoking. STUDY
      DESIGN: Plasma samples were obtained throughout pregnancy from 63 primiparous
      women with normal pregnancies. The samples were assayed for cellular fibronectin,
      vascular cell adhesion molecule-1, and intracellular adhesion molecule-1. Smoking
      status was determined by urinary cotinine concentrations. RESULTS: Mean cellular
      fibronectin concentrations were different by time (P<.001) and smoking status
      (P=.01); the lowest concentrations were found in smokers. In contrast,
      intracellular adhesion molecule-1 was different by smoking status (P=.046); the
      highest concentrations were found in smokers. Vascular cell adhesion molecule-1
      was different over time (P<.001), but not by smoking status. CONCLUSION: Smoking
      during pregnancy is associated with reduced cellular fibronectin and increased
      intracellular adhesion molecule-1. These differences may be the result of
      different aspects of endothelial function or the source of the marker. The
      explanation for reduced preeclampsia in smokers remains elusive.

PMID- 14586380
TI  - American Society for Clinical Pharmacology and Therapeutics position statement on
      the public health risks of ephedra.

PMID- 14586381
TI  - Label development and the label comprehension study for over-the-counter drugs.

PMID- 14586382
TI  - Impact of ontogeny on linezolid disposition in neonates and infants.
AB  - The impact of age on linezolid disposition during the first few months of life
      has not been previously investigated. We characterized linezolid pharmacokinetics
      after a single, 10.0-mg/kg intravenous dose in 42 infants stratified as follows:
      group 1 (n = 9), gestational age <34 weeks and postnatal age <8 days; group 2 (n
      = 7), gestational age <34 weeks and postnatal age 8 days to 12 weeks; group 3 (n
      = 11), gestational age >or=34 weeks and postnatal age <8 days; and group 4 (n =
      15), gestational age >or=34 weeks and postnatal age 8 days to 12 weeks. Linezolid
      was quantitated by a validated HPLC-triple-quadrupole mass spectrometer method
      from repeated blood samples (n = 7, 0.3 mL each) obtained over a 12-hour period.
      Pharmacokinetic parameters were determined by standard model-dependent
      techniques. The values (mean +/- SD) for total body clearance (CL) (0.25 +/- 0.12
      L x h(-1) x kg(-1)), apparent volume of distribution (VD(ss)) (0.75 +/- 0.19
      L/kg), and elimination half-life (t(1/2)) (2.8 +/- 2.1 hours) from the entire
      study cohort were similar to values reported previously for children and
      adolescents. Examination of the linezolid pharmacokinetics as a function of age
      revealed that CL increased rapidly during the first week of life and as a
      function of postnatal age. Age stratification revealed lower values for CL in
      those infants aged less than 8 days (group 1, 0.12 +/- 0.06 L x h(-1) x kg(-1);
      group 3, 0.23 +/- 0.12 L x h(-1) x kg(-1)) as compared with those aged 8 days to
      12 weeks (group 2, 0.31 +/- 0.07 L x h(-1) x kg(-1); group 4, 0.31 +/- 0.10 L x
      h(-1) x kg(-1)). In contrast to the results for CL, gestational age served to be
      the most useful predictor of VD(ss). Evaluation of the pharmacokinetic data would
      appear to support the use of linezolid dosing regimens currently approved for
      infants and young children in neonates with postnatal age greater than 7 days.

PMID- 14586383
TI  - Multiple transport mechanisms involved in the intestinal absorption and first
      pass extraction of fexofenadine.
AB  - OBJECTIVE: Our objective was to investigate the main in vivo transport mechanisms
      of fexofenadine involved in the intestinal absorption and bioavailability of the
      drug in humans. METHODS: A jejunal single-pass perfusion study was performed in
      10 healthy volunteers. Each experiment lasted for 200 minutes and was divided
      into 2 periods of 100 minutes. During the control period (0-100 minutes), the
      jejunal segment was perfused with 100 mg/L (186-micromol/L) fexofenadine. In the
      treatment period (100-200 minutes), fexofenadine was coperfused with 500 mg/L
      (1018-micromol/L) of the membrane transport inhibitor verapamil. The
      concentrations of fexofenadine in the perfusate and plasma were measured by HPLC
      with ultraviolet and mass detection, respectively. RESULTS: Verapamil did not
      significantly affect the human effective jejunal permeability of fexofenadine.
      The mean (+/-SD) effective jejunal permeability values were 0.06 +/- 0.07. 10(-4)
      cm/s and 0.04 +/- 0.07. 10(-4) cm/s in the control and treatment periods,
      respectively. However, verapamil increased the apparent absorption rate constant
      into the systemic circulation and the area under the plasma concentration-time
      curve for fexofenadine from 0.0030 +/- 0.0012 min(-1) to 0.0255 +/- 0.0103 min(
      1) (P <.001) and from 161 +/- 181 ng/mL x min to 664 +/- 537 ng/mL x min (P
      <.01), respectively. CONCLUSIONS: In this in vivo perfusion study verapamil
      increased the bioavailability of fexofenadine. Because the permeability, which is
      a direct measure of intestinal transport, was unchanged, we suggest that the
      major reason for this effect was decreased first-pass liver extraction of
      fexofenadine. The most plausible mechanism is either decreased organic anion
      transporting polypeptide-mediated sinusoidal uptake or P-glycoprotein-mediated
      canalicular secretion of fexofenadine, or both.

PMID- 14586384
TI  - Combined phenotypic assessment of cytochrome p450 1A2, 2C9, 2C19, 2D6, and 3A, N
      acetyltransferase-2, and xanthine oxidase activities with the "Cooperstown 5+1
      cocktail".
AB  - Previously, we have validated a 4-drug phenotyping cocktail, the "Cooperstown
      cocktail," using caffeine (cytochrome p450 [CYP] 1A2, N-acetyltransferase-2
      [NAT2], and xanthine oxidase [XO]), dextromethorphan (CYP2D6), omeprazole
      (CYP2C19), and intravenous midazolam (hepatic CYP3A). Data suggest that warfarin
      can be used as a safe and accurate biomarker for CYP2C9, and if warfarin is
      administered with vitamin K, the pharmacodynamic effect is ablated. Twelve
      subjects received the Cooperstown cocktail, warfarin plus vitamin K, and both
      sets of biomarkers (Cooperstown 5+1 cocktail) in a randomized crossover fashion.
      On the basis of log-transformed data and a paired t test, no significant
      difference was seen for S-warfarin area under the serum concentration-time curve
      from time 0 to infinity (P =.09), omeprazole metabolic ratio (P =.374), caffeine
      metabolic ratio (P =.169 for CYP1A2 activity), midazolam plasma clearance (P
      =.573), or dextromethorphan metabolic ratio (P =.747) with the Cooperstown
      cocktail, warfarin plus vitamin K alone, or the Cooperstown 5+1 cocktail. During
      drug administration, the only side effect was mild and short-lived sedation after
      intravenous midazolam administration. Phenotypic measurements were in concordance
      with the subject's CYP2C9, CYP2C19, and CYP2D6 genotypes. The Cooperstown 5+1
      cocktail may be used to simultaneously assess the activities of CYP1A2, CYP2C9,
      CYP2C19, CYP2D6, CYP3A, NAT2, and XO.

PMID- 14586385
TI  - Cytochrome p450 3A4 messenger ribonucleic acid induction by rifampin in human
      peripheral blood mononuclear cells: correlation with alprazolam pharmacokinetics.
AB  - OBJECTIVE: There is significant interest in the assessment of the individual
      cytochrome p450 (CYP) 3A4 activity. We analyzed whether CYP3A4 messenger
      ribonucleic acid (mRNA) concentrations in leukocytes reflect CYP3A activity in
      the liver measured by alprazolam as an in vivo probe drug. We also wanted to
      identify whether genetically determined high CYP3A5 expression is associated with
      increased alprazolam clearance. METHODS: Alprazolam plasma concentrations were
      measured 10 hours after intake of 1 mg alprazolam. CYP3A4 mRNA concentrations in
      peripheral blood mononuclear cells were quantified in 96 healthy volunteers
      before and after 5-day treatment with 450 mg rifampin (INN, rifampicin) daily.
      Genetic polymorphisms in CYP2C19, CYP3A4, and CYP3A5 were analyzed by polymerase
      chain reaction, restriction fragment length polymorphism, and sequencing.
      RESULTS: The median alprazolam concentration measured 10 hours after dosage was
      8.1 mug/L (range, 4.5-14.6 mug/L) before and 1.7 mug/L (range, 0.3-4.1 mug/L)
      after rifampin treatment. Leukocyte CYP3A4 mRNA was detectable in all samples
      with a median of 28 molecules per 1 ng total ribonucleic acid before (range, 10
      128 molecules per 1 ng total ribonucleic acid) and 50 molecules per 1 ng total
      ribonucleic acid after (range, 9-484 molecules per 1 ng total ribonucleic acid)
      rifampin treatment (P <.001). However, mRNA concentrations before and during
      rifampin induction were largely overlapping, and there was a poor correlation
      between mRNA concentrations and alprazolam 10-hour trough concentrations
      reflecting CYP3A4 activity (r = -0.4, P <.001). Alprazolam kinetics did not
      differ between genetically determined expressers of CYP3A5 (genotype CYP3A5*1/*3)
      compared with homozygous carriers of the splice site variant. A marginally
      significant dependence of alprazolam concentrations from the CYP2C19 allele *2
      was found (P =.04). CONCLUSIONS: CYP3A4 mRNA concentrations in blood cells were
      very low and did not reflect systemic drug clearance mediated by CYP3A enzymes.
      The CYP3A5 genetic polymorphism does not appear relevant for alprazolam kinetics.

PMID- 14586386
TI  - Impact of serum creatinine measurement error on dose adjustment in renal failure.
AB  - BACKGROUND: Doses of renally eliminated drugs should be adjusted according to
      kidney function to prevent adverse drug events and cost. Dose adjustment can be
      based on serum creatinine level, subsequent creatinine clearance estimation, and
      dosage calculation with consideration of the renal elimination properties of the
      respective compound. OBJECTIVE: Our objective was to quantify the impact and
      relevance of serum creatinine measurement error on dose adjustment in renal
      failure. METHODS: We analyzed 27914 measurements from external quality assessment
      surveys of 1878 German laboratories that used a kinetic alkaline picrate (69% of
      results) or an enzymatic method (25%) for creatinine determination. Linear models
      were fit for both methods combined and separately. On the basis of 95% confidence
      intervals (CIs) for creatinine values, 95% CIs for drug dosing were calculated.
      RESULTS: The 95% CI for a measured serum creatinine value was 0.80. Measured
      value < Reference method value < 1.28. Measured value for the kinetic alkaline
      picrate method and 0.87. Measured value < Reference method value < 1.21. Measured
      value for the enzymatic method. Applied to a data set of 6.5 million simulated
      patients with all possible combinations of characteristics relevant for drug
      dosing, the dosing error caused by serum creatinine measurement error did not
      exceed 25% in patients with creatinine clearance estimates lower than 50 mL/min
      according to the Cockcroft-Gault equation. For drugs completely eliminated by the
      kidneys in active form, the dosing error was up to 6-fold smaller than that which
      would occur if doses were not adjusted. CONCLUSION: The serum creatinine
      measurement error of current laboratory methods is small and is comparable to
      other errors influencing dose adjustment.

PMID- 14586387
TI  - Effects of cigarette smoking and carbon monoxide on chlorzoxazone and caffeine
      metabolism.
AB  - OBJECTIVES: Our objectives were to examine the effects of cigarette smoking on
      the disposition kinetics of chlorzoxazone and caffeine as probes of cytochrome
      p450 (CYP) 2E1, CYP1A2, xanthine oxidase, and N-acetyltransferase-2 activity and
      to test the hypothesis that carbon monoxide inhibits drug metabolism via these
      pathways. METHODS: Twelve cigarette smokers were studied in 3 treatment
      conditions, each lasting 7 days, during which they smoked cigarettes, breathed
      carbon monoxide to achieve carboxyhemoglobin levels similar to those associated
      with cigarette smoking, or breathed air. In each treatment condition, subjects
      received oral chlorzoxazone (250 mg) and caffeine (250 mg) with measurement of
      disposition kinetics and urine metabolite profiles. RESULTS: Compared with the
      air condition, cigarette smoking significantly induced the metabolism of
      chlorzoxazone (oral clearance, 5.9 +/- 1.5 mL x min(-1) x kg(-1) versus 4.8 +/-
      1.0 mL x min(-1) x kg(-1), P <.005) and caffeine (2.0 +/- 0.8 mL x min(-1) x kg(
      1) versus 1.5 +/- 0.7 mL x min(-1) x kg(-1), P <.001) but had no effect on
      caffeine urine metabolite ratios that reflect xanthine oxidase and N
      acetyltransferase-2 activity. Considerable individual variability was noted in
      the extent of induction of metabolism by cigarette smoking, particularly as it
      affects chlorzoxazone (change in oral clearance ranged from -10% to +71%). Carbon
      monoxide had no effect on chlorzoxazone or caffeine metabolism or caffeine
      metabolic profile. CONCLUSIONS: This study provides novel evidence that cigarette
      smoking accelerates chlorzoxazone metabolism, most likely reflecting induction of
      CYP2E1 activity, in humans. Induction of CYP2E1 activity by cigarette smoking
      could contribute to tobacco-induced cancer, alcohol-induced liver disease, and
      the risk of acetaminophen hepatotoxicity.

PMID- 14586388
TI  - The bioavailability of intranasal and smoked methamphetamine.
AB  - BACKGROUND: Patients in harm-reduction treatment programs are switching from
      intravenous to other routes of methamphetamine (INN, metamfetamine)
      administration to avoid risks associated with needle use. Relatively little has
      been reported about the bioavailability of methamphetamine when smoked or used
      intranasally. METHODS: Eight experienced methamphetamine users were administered
      smoked or intranasal methamphetamine concurrently with an intravenous dose of
      deuterium-labeled methamphetamine. Plasma and urine concentrations were measured
      for calculation of bioavailability and other pharmacokinetic parameters by
      noncompartmental methods. RESULTS: Methamphetamine was well absorbed after
      smoking or intranasal administration, with bioavailabilities of 79% after
      intranasal administration and 67% of the estimated delivered dose or 37.4% of the
      absolute (pipe) dose after smoking. Maximum methamphetamine concentrations
      occurred at 2.7 and 2.5 hours after intranasal and smoked doses. The elimination
      half-life was similar for intravenous (11.4 hours), intranasal (10.7 hours), and
      smoked (10.7 hours) methamphetamine. Clearance (272 mL x h(-1) x kg(-1)), steady
      state volume of distribution (4.2 L/kg), and mean residence time (16 hours) of
      the intravenous dose were similar to previously reported values.
      Dextroamphetamine (INN, dexamfetamine) half-life (all routes) was 16.2 hours.
      Methamphetamine and dextroamphetamine renal clearances (all routes) were about
      100 and 1100 mL x h(-1) x kg(-1), respectively. CONCLUSIONS: Intranasal and
      smoked methamphetamine are well absorbed. Although intranasal or smoked routes
      may decrease the risk of transmission of blood-borne diseases, exposure to
      methamphetamine and the possibility of drug-related complications remain
      substantial.

PMID- 14586389
TI  - No effect of MDR1 C3435T variant on loperamide disposition and central nervous
      system effects.
AB  - BACKGROUND: The MDR1 gene encodes the efflux transporter P-glycoprotein, which is
      highly expressed in the small intestine and in the blood-brain barrier. A major
      function of P-glycoprotein is to limit the absorption and central nervous system
      exposure of numerous xenobiotics. A genetic polymorphism in the MDR1 gene
      (C3435T) has been associated with changes in the intestinal expression level and
      function of P-glycoprotein. The aim of this study was to investigate the effect
      of this polymorphism on disposition and brain entry of the P-glycoprotein
      substrate loperamide. METHODS: Healthy white volunteers were genotyped for the
      MDR1 C3435T polymorphism, and a 16-mg oral dose of loperamide was administered to
      8 subjects with the 3435TT genotype and 8 subjects with the 3435CC genotype.
      Plasma levels of loperamide were determined by liquid chromatography-tandem mass
      spectrometry. Loperamide-induced respiratory depression was detected as the
      ventilatory response to carbon dioxide and was used as a measure of central
      nervous system side effects. RESULTS: We found no significant difference in
      loperamide pharmacokinetics between individuals homozygous for the C and the T
      alleles in position 3435 of MDR1, as follows: peak plasma drug concentration,
      3164 +/- 1053 pg/mL and 3021 +/- 984 pg/mL; area under the concentration-time
      curve from 0 to 8 hours, 14414 +/- 4756 pg. h/mL and 14923 +/- 6466 pg. h/mL; and
      time to peak plasma drug concentration, 3.9 +/- 1.4 hours and 3.9 +/- 2.6 hours
      for the MDR1 3435CC and 3435TT genotypes, respectively (P >.05, for all
      parameters). Hypercapnic ventilatory response changed only minimally after
      ingestion of loperamide (the coefficient of variation during the 0- to 8-hour
      period was 21% +/- 14% for the sample population), and there was no MDR1 3435
      genotype-related effect on respiratory response. Carriers of the 2 major MDR1
      haplotypes, MDR1*1 and MDR1*13, did not differ in their response to loperamide.
      CONCLUSION: There was no association between the MDR1 C3435T variation and plasma
      levels or central nervous system effects of the P-glycoprotein substrate
      loperamide in a white study population. The MDR1 haplotype structure was quite
      variable and supports the use of haplotypes instead of single nucleotide
      polymorphisms in determining clinical consequences of genetic variation.

PMID- 14586390
TI  - Venous response to nitroglycerin is enhanced in young, healthy carriers of the
      825T allele of the G protein beta3 subunit gene (GNB3).
AB  - OBJECTIVE: The ultimate mode of action by which nitroglycerin elicits
      vasodilation remains elusive. Animal studies point to an involvement of pertussis
      toxin-sensitive G proteins. The 825T allele of the GNB3 C825T polymorphism in the
      gene encoding the G protein beta3 subunit is associated with enhanced signal
      transduction via pertussis toxin-sensitive pathways in vitro. We hypothesized
      that G proteins have a role in nitroglycerin-mediated vasodilation and that
      carriers of the 825T allele would exhibit a stronger response to nitroglycerin.
      METHODS: We used the linear variable transducer technique to compare dorsal hand
      vein compliance in 28 young, healthy men with and without the T allele (n = 15
      CC, n = 8 CT, and n = 5 TT). After individual dose-response curves to
      phenylephrine had been established, veins were preconstricted to 70% of the
      maximal phenylephrine-induced constriction. Nitroglycerin was then infused in
      ascending doses (0.02-2000 ng/min), and the vasodilatory response was measured.
      RESULTS: The vasodilatory response to nitroglycerin was significantly greater in
      carriers of the 825T allele. The maximal response to nitroglycerin was 102% +/-
      6% venodilation in the CT/TT group and 78% +/- 5% in the CC control group (P
      =.0045) (mean difference, -24% +/- 8%; 95% confidence interval, 8%-40%).
      Comparison of the nitroglycerin dose-response curves by ANOVA confirmed an
      enhanced nitroglycerin-induced venodilation in 825T-allele carriers (P <.0001).
      CONCLUSION: Our results suggest that the GNB3 C825T polymorphism determines
      venous response to nitroglycerin and that G proteins may be involved in the
      signal transduction pathway.

PMID- 14586391
TI  - Altered pharmacokinetics and excessive hypotensive effect of candesartan in a
      patient with the CYP2C91/3 genotype.
AB  - An 89-year-old man with severe hypertension (190/82 mm Hg) and chronic heart
      failure (New York Heart Association class II) despite treatment with benidipine,
      doxazosin mesylate (INN, doxazosin), and furosemide was given oral candesartan
      cilexetil (4 mg/d), an angiotensin II type 1 receptor blocker metabolized via
      cytochrome p450 (CYP) 2C9. Two days later, he started to have severe dizziness
      and returned to the hospital on the fourth day without taking any of his
      medications. The blood pressure 30 hours after the last dose of candesartan was
      126/64 mm Hg. Polymorphism analysis revealed the heterozygous poor metabolizer
      genotype CYP2C9*1/*3. The area under the concentration-time curve and the mean
      residence time of candesartan were both increased 2.5-fold, and the oral
      clearance of candesartan was 48% lower than that of the average elderly Japanese
      patient with hypertension. These results suggest that the CYP2C9*1/*3 genotype
      could be associated with decreased clearance and increased plasma concentration
      of candesartan, potentially enhancing its hypotensive effect.

PMID- 14586392
TI  - Disposition of polyoxyethylated excipients in humans: implications for drug
      safety and formulation approaches.

PMID- 14586394
TI  - Clinical trial efficacy: what does it really tell you?
AB  - The primary goal of most clinical trials is an evaluation of the efficacy of the
      drug being evaluated. Therefore, it is important to understand if study outcomes
      are a true reflection of a drug's "real-life" effectiveness. Clinical trials
      generally evaluate three types of outcomes: subjective, objective, and health
      related. Clinical trials that use subjective measures as endpoints usually
      evaluate outcomes such as symptom scores, the need for rescue medication, and
      quality-of-life measures. The majority of clinical trials rely on objective
      measures to test the efficacy of asthma medications. These include lung function
      (peak expiratory flow rate, forced expiratory volume at one second [FEV1]), level
      of bronchial hyperresponsiveness (methacholine challenge or exercise challenge),
      and markers of inflammation (exhaled nitric oxide, sputum eosinophils,
      bronchoalveolar lavage, and bronchial biopsy). FEV1 remains the gold standard of
      efficacy measures; however, in pediatrics, where FEV1 values are often within the
      normal range, re-adjustment of what constitutes various levels of asthma severity
      should occur. Occasionally, studies will include an assessment of health
      outcomes, either as a primary or secondary measure, during the course of the
      study. Commonly measured health outcomes include a reduction in need for rescue
      systemic glucocorticoids, a reduction in the need for emergent asthma care, a
      reduction in asthma hospitalizations, and a reduction in asthma deaths. Studies
      designed to assess impact of treatment regimens on morbidity and mortality remain
      a high priority, as do studies designed to predict response to current asthma
      therapies.

PMID- 14586395
TI  - Clinical trials: are these your patients?
AB  - Many clinicians base their treatment choices on trial outcomes. To determine if
      clinical trial results apply to the general patient population, several factors
      need to be considered. The exclusion and inclusion of patients in a trial may
      present selection bias. Adherence to therapy in trials often varies widely
      compared with adherence seen in clinical practice. Endpoints used in trials
      compared with endpoints used in practice are not always comparable. The
      performance and publication of clinical trials can be affected by investigator or
      publication bias. Finally, reporting of data as mean values may not always relate
      to the outcome in individual patients. By understanding some of these issues,
      clinicians can begin to better relate trial results with patient treatment
      options.

PMID- 14586396
TI  - Considering therapeutic options in the real world.
AB  - When choosing a drug regimen, physicians can rely on two models: their own
      clinical experience and results from clinical trials. Both options have problems.
      Overall, patients with persistent asthma symptoms often have improved outcomes
      with the use of long-term controller medications on a daily basis to prevent
      exacerbations of symptoms. Inhaled corticosteroids (ICSs) are generally
      recognized as being the most effective treatment for the underlying inflammatory
      characteristics of asthma. However, despite adequate dosing, some patients with
      persistent asthma remain symptomatic while taking an ICS. Therefore, it may be
      beneficial to administer combination therapy with an ICS and a long-acting beta
      agonist (LABA) in this subset of asthma patients. Another anti-inflammatory
      choice for persistent asthma is the leukotriene receptor antagonist (LTRA),
      either as monotherapy or in combination with an ICS. Regardless of what treatment
      regimen a physician chooses to prescribe, the choice of medication depends on
      many factors, including patient preference, physician comfort with the regimen,
      and cost.

PMID- 14586397
TI  - Allele-specific patterns of the mouse parathyroid hormone-related protein:
      influences on cell adhesion and migration.
AB  - The mouse parathyroid hormone-like hormone Pthlh(Pro) and Pthlh(Thr) variants are
      linked with susceptibility and resistance to skin carcinogenesis of Car-S and Car
      R mice, respectively, and with in vitro effects (Oncogene, 19: 5324-5328, 2000).
      We have identified an additional Pthlh variant, consisting of Thr and three amino
      acid changes in the C-terminus (Pthlh(SerAspTyr)), carried by an evolutionarily
      distant Mus spretus (SPRET/Ei) inbred strain. When transfected into NCI-H520
      tumor cells, this Pthlh(SerAspTyr) variant did not stimulate tumor growth in nude
      mice. Analysis of cell adhesion, migration, and invasion patterns of Pthlh(Pro)-,
      Pthlh(Thr)-, and Pthlh(SerAspTyr)-transfected NCI-H520 cells revealed a 1.5-fold
      decrease in adhesion efficiency on both collagen type I and Matrigel, and a 5-6
      fold increase in migration capability in Pthlh(Pro) transfectants as compared to
      nontransfected, vector-transfected, Pthlh(Thr)-, or Pthlh(SerAspTyr)-transfected
      cells. These findings suggest that the cancer modifier effects of the mouse Pthlh
      gene are mediated by differential cell adhesion and migration effects of PTHrP
      variants.

PMID- 14586398
TI  - Tumor suppressor p53 inhibits transcriptional activation of invasion gene
      thromboxane synthase mediated by the proto-oncogenic factor ets-1.
AB  - Cancer formation and progression is a complex process determined by several
      mechanisms that promote cell growth, invasiveness, neo-angiogenesis, and render
      neoplastic cells resistant to apoptosis. The tumor suppressor p53 and the proto
      oncogenic factor ets-1 are important regulators of such mechanisms. While it is
      well established that p53 and ets-1 influence various aspects of cell behavior by
      regulating the transcription of specific genes, little is known about the
      functional relationship between these transcription factors. We found that the
      gene encoding thromboxane synthase (TXSA), which we recently identified as a
      factor promoting invasion and resistance to apoptosis in gliomas, is a novel
      target gene for both p53 and ets-1. We demonstrate that p53 and ets-1 coregulate
      TXSA in an antagonistic and inter-related manner, with ets-1 being a potent
      transcriptional activator and p53 inhibiting ets-1-dependent transcription.
      Negative interference with ets-1 transcription requires functional p53 and is
      lost in mutant p53 proteins. We show that ets-1 and p53 associate physically in
      vitro and in vivo and that their interaction, rather than a direct binding of p53
      to the TXSA promoter, is required for transcriptional repression of TXSA by wild
      type p53. An important implication of our findings is that the loss of p53
      mediated negative control over ets-1-dependent transcription may lead to the
      acquisition of an invasive phenotype in tumor cells.

PMID- 14586399
TI  - MAPK phosphatase DUSP16/MKP-7, a candidate tumor suppressor for chromosome region
      12p12-13, reduces BCR-ABL-induced transformation.
AB  - Recurrent chromosome 12p deletions are associated with distinct tumor types and
      suggest the presence of a tumor suppressor gene (TSG). Previously, we mapped an
      EST with similarity to a protein tyrosine phosphatase to the minimally deleted
      region for all these neoplasms. The corresponding gene, DUSP16/MKP-7, was
      recently shown to code for a mitogen-activated protein kinase phosphatase,
      suggestive for a function as tumor suppressor. Overexpression of DUSP16 in BCR
      ABL-transformed Rat-1 fibroblasts reduces their transforming capacity in vitro
      and in vivo via downregulation of BCR-ABL-induced JNK activation. A role for
      DUSP16 as a regulator of JNK signaling was further demonstrated via
      overexpression in Ba/F3 cells, which increased their antiapoptosis. However, no
      inactivating mutations could be detected in leukemia patients hemizygous for
      DUSP16, and the effect of hemizygosity on DUSP16 expression level could not be
      assessed due to the variability of DUSP16 transcript levels observed in leukaemia
      cell lines and in patients. Taken together, the functional data point to a
      context-dependent role for DUSP16 on cell transformation and apoptosis,
      reflecting the dual role of JNK, and therefore suggest that DUSP16 might be
      haploinsufficient for tumor suppression.

PMID- 14586400
TI  - Role of promoter methylation in regulation of the mammalian heparanase gene.
AB  - Mammalian heparanase (endo-beta-glucuronidase) degrades heparan sulfate
      proteoglycans and is an important modulator of the extracellular matrix and
      associated factors. The enzyme is preferentially expressed in neoplastic tissues
      and contributes to tumour metastasis and angiogenesis. To investigate the
      epigenetic regulation of the heparanase locus, methylation-specific and bisulfite
      PCR were performed on a panel of 22 human cancer cell lines. Cytosine methylation
      of the heparanase promoter was associated with inactivation of the affected
      allele. Despite lack of sequence homology, extensively methylated CpG islands
      were found both in human choriocarcinoma (JAR) and rat glioma (C-6) cells which
      lack heparanase activity. Treatment of these cells with demethylating agents (5
      azacytidine, 5-aza-2'-deoxycytidine) resulted in stable dose- and time-dependant
      promoter hypomethylation accompanied by reappearance of heparanase mRNA, protein
      and enzymatic activity. An inhibitor of histone deacetylase, Trichostatin A,
      failed to induce either of these effects. Upregulation of heparanase expression
      and activity by demethylating drugs was associated with a marked increase in lung
      colonization by pretreated C-6 rat glioma cells. The increased metastatic
      potential in vivo was inhibited in mice treated with laminaran sulfate, a potent
      inhibitor of heparanase activity. We propose a model wherein expression of
      mammalian heparanase gene is modulated by the interplay between trans-activating
      genetic and cis-inhibitory epigenetic elements in its promoter.

PMID- 14586401
TI  - Vav-promoter regulated oncogenic fusion protein NPM-ALK in transgenic mice causes
      B-cell lymphomas with hyperactive Jun kinase.
AB  - Anaplastic large-cell lymphoma is associated with a chromosomal translocation
      generating an oncogenic fusion protein: the nucleophosmin-anaplastic lymphoma
      kinase (NPM-ALK). We have generated several independent lines of human NPM-ALK
      transgenic mice using the haematopoietic cell-specific Vav promoter. Lymphomas
      develop in two transgenic lines in which the Vav promoter regulates NPM-ALK
      expression. The transgenic line with higher copy number displays an early-onset
      phenotype in which all mice succumb to aggressive lymph node tumours with
      intestinal involvement, whereas the second line displays late-onset tumour
      development in the spleen and/or liver. Lymphomas from both lines are
      phenotypically distinct and display B-lineage characteristics with aberrant
      coexpression of myeloid markers. The NPM-ALK kinase is active in primary tumour
      tissue and forms a multimeric complex with tyrosine-phosphorylated proteins, that
      is, Shc. Jun and ERK kinase activities in tumours are elevated by up to 30-fold
      and fivefold, respectively, in comparison with sIgM-stimulated primary B cells.
      The new transgenic models provide a system for investigating the oncogenic events
      mediated by NPM-ALK in situ and a physiologically relevant context for developing
      tyrosine kinase inhibitor therapies of potential use in the clinic.

PMID- 14586402
TI  - p53-independent induction of Gadd45 by histone deacetylase inhibitor: coordinate
      regulation by transcription factors Oct-1 and NF-Y.
AB  - Histone deacetylase (HDAC) inhibitors cause growth arrest at the G1 and/or G2/M
      phases, and induce differentiation and/or apoptosis in a wide variety of tumour
      cells. The growth arrest at G1 phase by HDAC inhibitors is thought to be highly
      dependent on the upregulation of p21/WAF1, but the precise mechanism by which
      HDAC inhibitors cause G2/M arrest or apoptosis in tumour cells is unknown. Gadd45
      causes cell cycle arrest at the G2/M phase transition and participates in
      genotoxic stress-induced apoptosis. We show here that it is also induced by a
      typical HDAC inhibitor, trichostatin A (TSA), through its promoter, in a p53
      independent manner. To identify the mechanism of activation of the gadd45
      promoter, we performed luciferase reporter analyses and electrophoretic mobility
      shift assays. These revealed that both the Oct-1 and CCAAT sites are needed for
      the full activation by TSA. We also found that the transcription factors Oct-1
      and NF-Y specifically bind to each site. Thus, HDAC inhibitors can induce Gadd45
      through its promoter without the need for functional p53, and both the Oct-1 and
      NF-Y concertedly participate in TSA-induced activation of the gadd45 promoter.

PMID- 14586403
TI  - MEK kinase 1 mediates the antiapoptotic effect of the Bcr-Abl oncogene through NF
      kappaB activation.
AB  - Bcr-Abl tyrosine kinase, a chimeric oncoprotein responsible for chronic
      myelogenous leukemia, constitutively activates several signal transduction
      pathways that stimulate cell proliferation and prevent apoptosis in hematopoietic
      cells. The antiapoptotic function of Bcr-Abl is necessary for hematopoietic
      transformation, and also contributes to leukemogenesis. Herein, we show for the
      first time that cell transformation induced by Bcr-Abl leads to increased
      expression and kinase activity of MEK kinase 1 (MEKK1), which acts upstream of
      the c-Jun N-terminal kinase (JNK), extracellular signal regulated kinase (ERK)
      and NF-kappaB signaling pathways. Inhibition of MEKK1 activity using a dominant
      negative MEKK1 mutant (MEKK1km) diminished the ability of Bcr-Abl to protect
      cells from genotoxin-induced apoptosis, but had no effect on the proliferation of
      Bcr-Abl-transformed cells. Expression of MEKK1km also reduced NF-kappaB
      activation, and inhibited antiapoptotic c-IAP1 and c-IAP2 mRNA expression in
      response to the genotoxin. By contrast, neither JNK nor ERK activation was
      affected. These results indicate that MEKK1 is a downstream target of Bcr-Abl,
      and that the antiapoptotic effect of Bcr-Abl in chronic myelogenous leukemia
      cells is mediated via the MEKK1-NF-kappaB pathway.

PMID- 14586404
TI  - Autocrine-mediated ErbB-2 kinase activation of STAT3 is required for growth
      factor independence of pancreatic cancer cell lines.
AB  - Pancreatic ductal adenocarcinoma (PDAC) cell lines, MIA PaCa-2, and UK Pan-1,
      were used to investigate the role of ErbB2 in PDAC oncogenesis. Both these cell
      lines exhibit exogenous growth factor-independent proliferation that was
      attributed to the production of autocrine growth factors and/or overexpression of
      growth factor receptors. The exogenous growth factor-independent phenotype
      displayed by these PDAC cell lines was dependent on ErbB2 kinase activity since
      treatment of cells with tyrphostin AG879 prevented serum-free media (SFM)
      induction of cell proliferation. We determined that ErbB2 kinase contributed to
      aberrant cell cycle regulation in PDAC through the induction of cyclin D1 levels
      and the suppression of p21(Cip1) and p27(Kip1). Inhibition of ErbB2 kinase led to
      cell cycle arrest marked by an increased association of p27(Kip1) with cdk2 and
      reduced levels of phosphorylated pRb. We further observed constitutive STAT3
      activation in the PDAC cell lines and an increase in STAT3 activation upon
      stimulating quiescent cells with SFM. Inhibitors of ErbB2 kinase blocked STAT3
      activation, whereas inhibition of EGFR kinase led to a slight reduction of STAT3
      activation. STAT3 was coimmunoprecipitated with ErbB2. SFM stimulation caused an
      increase in the association of ErbB2 and STAT3, which was blocked by inhibition
      of ErbB2 kinase. Expression of a STAT3 dominant negative prevented SFM-stimulated
      cell proliferation of MIA PaCa-2 cells, suggesting that activation of STAT3 by
      ErbB2 is required for a growth factor-independent phenotype of these cells.
      Consistent with this observation in PDAC cell lines, we found that most PDAC
      tumor specimens (10 of 11) showed constitutive activation of STAT3 and that ErbB2
      was readily detected in most of these tumors (nine of 11). We believe that these
      findings indicate a novel mechanism of oncogenesis in PDAC and may suggest future
      therapeutic strategies in the treatment of PDAC.

PMID- 14586405
TI  - Induction of Notch signaling by tumor necrosis factor in rheumatoid synovial
      fibroblasts.
AB  - Rheumatoid arthritis (RA) is characterized by progressive inflammation associated
      with abberrant proliferation of synoviocytes. In order to explore the
      characteristics of rheumatoid synovial fibroblasts (RSF), we performed the
      comparative gene expression profile analysis between RSF and normal synovial
      fibroblasts (NSF) upon tumor necrosis factor (TNF) stimulation. As an initial
      screening for the genes preferentially induced by TNF in RSF compared with NSF,
      we have adopted a cDNA array containing well-defined sets of genes responsible
      for cell growth, cell fate determination, and cellular invasiveness.
      Differentially expressed genes of interest were confirmed using real-time RT-PCR.
      We found that TNF induced the expression of Notch-1, Notch-4, and Jagged-2 in
      RSF. The expression of these proteins was detected in the RA synovial tissues.
      The nucleus of RA synoviocytes showed strong staining with anti-Notch-1 and Notch
      4 antibody. TNF induced the nuclear translocation of Notch intracellular domain
      in RSF, indicating the elicitation of the Notch signaling. Notch-1, Notch-4, and
      Jagged-2 proteins were also detected in the developing synovium of mouse embryo.
      Thus, RSF may have re-acquired the primordial phenotype, accounting for the
      hyperproliferation and aggressive invasiveness, exhibiting tumor-like phenotype.

PMID- 14586406
TI  - Senescing oral dysplasias are not immortalized by ectopic expression of hTERT
      alone without other molecular changes, such as loss of INK4A and/or retinoic acid
      receptor-beta: but p53 mutations are not necessarily required.
AB  - Our previous work showed that acquisition of immortality at the dysplasia stage
      of oral cancer progression was consistently associated with four changes: loss of
      retinoic acid receptor (RAR)-beta and p16INK4A expression, p53 mutations and
      activation of telomerase. One atypical dysplasia (D17) that underwent delayed
      senescence after an extended lifespan showed loss of RAR-beta and p16INK4A/p14ARF
      expression, but retained functional wild-type p53 and telomerase was not
      activated. We now demonstrate that retroviral delivery of hTERT results in
      telomere lengthening and immortalization of D17 without loss of functional wild
      type p53 activity. In contrast, the expression of hTERT in two other typical
      mortal dyplasia cultures (that retain RAR-beta and p16INK4A expression) does not
      extend their lifespan, even though telomeres are lengthened.

PMID- 14586407
TI  - Interleukin-6 acts as an antiapoptotic factor in human esophageal carcinoma cells
      through the activation of both STAT3 and mitogen-activated protein kinase
      pathways.
AB  - The production of interleukin-6 (IL-6) has been discovered in a variety of human
      tumors. Here we report the expression of IL-6, IL-6 receptor alpha (IL-6Ralpha),
      and gp130 in human esophageal carcinoma tissues. We further demonstrate that IL-6
      protects an esophageal carcinoma cell line CE48T/VGH from apoptosis induced by
      staurosporine. IL-6 stimulation induced a rapid phosphorylation of gp130 and
      STAT3, and a dominant-negative STAT3 completely abolished the antiapoptotic
      effect. IL-6 also activated ERK 1/2 in CE48T/VGH cells. Inhibition of the ERK
      activation by PD98059 and transfection of a dominant-negative ERK2 completely
      blocked the protection of IL-6 against apoptosis. Thus, both STAT and MAP kinase
      pathways are responsible for the IL-6-delivered survival signal in human
      esophageal carcinoma cells. In contrast, PI3-K inhibitors only partially
      attenuated the effect of IL-6, suggesting that PI3-K does not play a major role
      in the antiapoptotic signal of IL-6 in our system. To investigate whether IL-6
      could induce the production of antiapoptotic molecules, proteins of the Bcl-2
      family were measured. While Bcl-2, Bcl-x(L,), and Bax were not affected, Mcl-1
      was induced by IL-6 in human esophageal carcinoma cells. Our results suggest that
      IL-6 may contribute to the progression of esophageal cancers in an autocrine or
      paracrine manner.

PMID- 14586408
TI  - TGF-beta-induced apoptosis in human thyrocytes is mediated by p27kip1 reduction
      and is overridden in neoplastic thyrocytes by NF-kappaB activation.
AB  - Millions of people worldwide suffer goiter, a proliferative disease of the
      follicular cells of the thyroid that may become neoplastic. Thyroid neoplasms
      have low proliferative index, low apoptotic index and a high incidence of
      metastasis. TGF-beta is overexpressed in thyroid follicular tumor cells. To
      investigate the role of TGF-beta in thyroid tumor progression, we established
      cultures of human thyrocytes from different proliferative pathologies (Grave's
      disease, multinodular goiter, follicular adenoma, papillary carcinoma), lymph
      node metastasis, and a normal thyroid sample. All cultures maintained the
      thyrocyte phenotype. TGF-beta induced cell-cycle arrest in all cultures, in
      contrast with results reported for other epithelial tumors. In deprived medium,
      TGF-beta induced apoptosis in normal thyrocyte cultures and all neoplastic
      cultures except the metastatic cultures. This apoptosis was mediated by a
      reduction in p27kip1 levels, inducing cell-cycle initiation. Antisense p27
      expression induced apoptosis in the absence of TGF-beta. By contrast, in cells in
      which p27 was overexpressed, TGF-beta had a survival effect. In growth medium, a
      net survival effect occurs in neoplastic thyrocytes only, not normal thyrocytes,
      due to activation of the NF-kappaB survival program. Together, these findings
      suggest that (a) thyroid neoplasms are due to reduced apoptosis, not increased
      division, in line with the low proliferative index of these pathologies, and (b)
      TGF-beta induces apoptosis in normal thyrocytes via p27 reduction, but that in
      neoplastic thyrocytes this effect is overridden by activation of the NF-kappaB
      program.

PMID- 14586409
TI  - Cooperativity of p19ARF, Mdm2, and p53 in murine tumorigenesis.
AB  - The p19ARF gene product responds to oncogenic stresses by interfering with the
      inhibitory effects of Mdm2 on p53, thus enhancing p53 activity and its
      antiproliferative functions. The absence of p19ARF in the mouse leads to early
      tumor susceptibility, presumably in part due to decreased p53 activity. To
      examine the tumorigenic cooperativity of p19ARF, Mdm2, and p53 in vivo, p19ARF
      deficient mice were crossed first to p53-deficient mice and then to Mdm2
      transgenic mice. The progeny were monitored for tumors. Cooperativity between
      p19ARF and p53 deficiencies in accelerating tumor formation was observed for most
      genotypes except p53-/- p19ARF-/- mice. p53-/- p19ARF-/- mice had a tumor
      incidence similar to p53-/- mice. In this context, tumor suppression by ARF
      appears to be primarily p53 dependent. The majority of the p19ARF+/- tumors
      deleted the wildtype p19ARF allele, in agreement with the previous studies,
      suggesting that p19ARF is a classic 'two hit' tumor suppressor. In a p53+/-
      background, however, all p19ARF+/- tumors retained a wildtype ARF allele and most
      also retained wildtype p53. In the second cross between p19ARF-deficient and Mdm2
      transgenic mice, cooperativity in tumor incidence between Mdm2 overexpression and
      ARF deficiency was observed, consistent with the role of p19ARF in negatively
      regulating Mdm2 activity. These experiments further demonstrate in vivo the inter
      relationships of the p19ARF-Mdm2-p53 signaling axis in tumor suppression.

PMID- 14586410
TI  - Interferon-gamma suppresses transforming growth factor-beta-induced invasion of
      gastric carcinoma cells through cross-talk of Smad pathway in a three-dimensional
      culture model.
AB  - We reconstituted a three-dimensional gastric carcinoma model similar to invasive
      gastric carcinoma tissue. This model consists of a human gastric carcinoma cell
      line, GCTM-1, a human fibroblast cell line, TIG-1-20, and transforming growth
      factor-beta (TGF-beta)-containing type I collagen gel. Using this model, we were
      able to observe the growth of the two cell types, especially carcinoma cell
      invasive growth, in real time for more than 30 days. TGF-beta and TIG-1-20 were
      essential for GCTM-1 invasive growth and proliferation, respectively. TGF-beta
      induced the enhanced expression of matrix metalloproteinase 9 (MMP9) and
      urokinase-type plasminogen activator (uPA) in GCTM-1 at both the protein and
      enzymatic activity levels. The TGF-beta-induced invasion of GCTM-1 was inhibited
      by MMP9- or uPA-antisense (AS) oligonucleotide transfection to GCTM-1. When
      exogenous interferon-gamma (IFN-gamma) was added to this model, TGF-beta
      dependent GCTM-1 invasion was significantly inhibited, concomitant with the
      decreased expression of MMP9 and uPA. The intracellular signal transduction of
      Smad was examined to analyse the mechanism of the inhibitory effect of IFN-gamma.
      TGF-beta accelerated the phosphorylation of Smad2/3 and nuclear translocation of
      the Smad2/3-Smad4 complex in GCTM-1, but these TGF-beta-induced effects were
      significantly inhibited by IFN-gamma-induced Smad7 expression. When GCTM-1 was
      cotransfected with AS oligonucleotide of Smad2 and Smad3, the TGF-beta-induced
      invasion of GCTM-1 disappeared. In addition, the inhibitory effect of IFN-gamma
      on TGF-beta-dependent GCTM-1 invasion vanished by the AS oligonucleotide of Smad7
      transfection. These results indicate that IFN-gamma inhibits TGF-beta-dependent
      GCTM-1 invasion through cross-talk in the Smad pathway. IFN-gamma may be a new
      therapeutic tool for TGF-beta-expressed invasive carcinomas.

PMID- 14586411
TI  - Different levels of control prevent interferon-gamma-inducible HLA-class II
      expression in human neuroblastoma cells.
AB  - The HLA class II expression is controlled by the transcriptional activator CIITA.
      The transcription of CIITA is controlled by different promoters, among which
      promoter-IV is inducible by IFN-gamma. We analysed the regulation of HLA class II
      molecules by IFN-gamma in a large series of human neuroblastoma cell lines. No
      induction of surface or intracellular HLA class II molecules and of specific mRNA
      was observed, in all neuroblastomas, with the exception of a nonprototypic cell
      line, ACN. In a large subset of neuroblastomas IFN-gamma induced expression of
      CIITA mRNA, derived from promoter-IV, which was not methylated. In contrast, in
      another subset of neuroblastomas, CIITA was not inducible by IFN-gamma and CIITA
      promoter-IV was either completely or partially methylated. Interestingly, the use
      of DNA demethylating agents restored CIITA gene transcriptional activation by IFN
      gamma, but not HLA class II expression. The defect of HLA class II was not
      related to alterations in RFX or NF-Y transcription factors, as suggested by EMSA
      or RFX gene transfection experiments. In addition, the transfection of a
      functional CIITA cDNA failed to induce HLA class II expression in typical
      neuroblastoma cells. Confocal microscopy and Western blot analysis suggested a
      defective nuclear translocation and/or reduced protein synthesis in CIITA
      transfected NB cells. Altogether, these data point to multiple mechanisms
      preventing HLA class II expression in the neuroblastoma, either involving CIITA
      promoter-IV silencing, or acting at the CIITA post-transcriptional level.

PMID- 14586412
TI  - Expression of the Ca2+-selective cation channel TRPV6 in human prostate cancer: a
      novel prognostic marker for tumor progression.
AB  - Members of the TRP superfamily of cation channels have homeostatic and regulatory
      functions in cells and changes in their expression may contribute to malignant
      growth. Previously, we have demonstrated that the gene of the Ca2+-selective
      cation channel CaT-L or TRPV6 is not expressed in benign prostate tissues
      including benign prostate hyperplasia, but is upregulated in prostate cancer.
      Here, we report on the differential expression of TRPV6 mRNA in prostate tissue
      obtained from 140 patients with prostate cancer. Using in situ hybridization,
      TRPV6 transcripts were undetectable in benign prostate tissue, high-grade
      prostatic intraepithelial neoplasia (n=57), incidental adenocarcinoma and all
      tumors less than 2.3 cubic centimeter (cc). In prostatectomy specimens from 97
      clinically organ-confined tumors, TRPV6 expression correlated significantly with
      the Gleason score (P=0.032), pathological stage (P<0.001) and extraprostatic
      extension (P=0.025). Lymph node metastasis (n=17) and androgen-insensitive tumors
      (n=27) revealed TRPV6 expression in 63 and 67% of cases, respectively. The
      latter, however, revealed markedly and significantly decreased levels when
      compared with untreated tumors (P=0.044). In summary, the data demonstrate that
      TRPV6 expression is associated with prostate cancer progression. Accordingly,
      TRPV6 represents a prognostic marker and, as a plasma membrane Ca2+ channel, a
      promising target for new therapeutic strategies to treat advanced prostate
      cancer.

PMID- 14586413
TI  - Epigenetic inactivation of RASSF1A candidate tumor suppressor gene at 3p21.3 in
      brain tumors.
AB  - The human Ras association domain family 1A (RASSF1A) gene, recently isolated from
      the lung and breast tumor suppressor locus 3p21.3, is highly methylated in
      primary lung, breast, nasopharyngeal and other tumors, and re-expression of
      RASSF1A suppresses the growth of several types of cancer cells. Epigenetic
      inactivation of RASSF1A by promoter hypermethylation is also important in the
      development of several human cancers. The methylation status of the promoter
      region of RASSF1A was analysed in primary brain tumors and glioma cell lines by
      methylation-specific polymerase chain reaction. In primary brain tumors, 25 of 46
      (54.3%) gliomas and five of five (100%) medulloblastomas showed RASSF1A
      methylation. In benign tumors, only one of 10 (10%) schwannomas and two of 12
      (16.7%) meningiomas showed RASSF1A methylation. The RASSF1A promoter region was
      methylated in all four glioma cell lines. RASSF1A was re-expressed in all
      methylated cell lines after treatment with the demethylating agent 5-aza-2'
      deoxycytidine. Methylation of the promoter CpG islands of the RASSF1A may play an
      important role in the pathogenesis of glioma and medulloblastoma.

PMID- 14586414
TI  - DNA damage-induced cell-cycle phase regulation of p53 and p21waf1 in normal and
      ATM-defective cells.
AB  - The ATM-dependent accumulation of p53 and induction of p21waf1 are key events for
      G1 cell-cycle checkpoint arrest following DNA damage. In ATM-null AT cells, even
      though the p53 and p21waf1 responses are kinetically delayed and quantitatively
      reduced, the G1 checkpoint is virtually disrupted, suggesting that these proteins
      arrive too late in G1 to enforce the arrest. As the precise mechanism remains
      unclear, we examined the response to DNA double-strand breaks generated by gamma
      radiation (IR), to determine if ATM deficiency affects the cell-cycle phase
      regulation of these molecules. We find that, after irradiation, whereas normal
      LCL-N cells markedly increase their levels of p53 in all phases of the cell
      cycle, AT cells fail to show any p53 increase in the G1 phase. In addition,
      whereas in LCL-N p21waf1 is induced in G1 and G2-M, in AT cells this induction is
      partly seen in G2-M, but not in G1, indicating a different cell-cycle phase
      regulation of p53 and p21waf1 as a result of ATM deficiency. The levels and
      catalytic activity of the p53-targeting kinases ATR and DNA-PK in LCL-N and AT
      cells are very similar throughout the cell cycle, both before and after IR, thus
      excluding a phase-specific activity for these kinases. Collectively, our findings
      demonstrate that, in ATM-deficient cells, the p53-dependent p21waf1 response to
      DNA damage is not only quantitatively reduced, but also specifically suppressed
      in the G1 phase, thus providing a mechanistic explanation for the severe
      disruption of the G1 checkpoint in AT cells.

PMID- 14586415
TI  - Betting on our future.

PMID- 14586416
TI  - The role of T-bet in B cells.

PMID- 14586418
TI  - On the nose: shared themes for the sensory and immune self.
AB  - The immune system and the central nervous system operate in very different ways,
      but the dual use of the major histocompatibility complex CD8+ T cell monitoring
      and pheromone presentation indicates some commonalities exist.

PMID- 14586419
TI  - Y in X priming.

PMID- 14586420
TI  - The latest killer AP.

PMID- 14586422
TI  - LFA-1: more than just T cell Velcro.

PMID- 14586421
TI  - I-Tim-izing the pathways of counter-regulation.

PMID- 14586424
TI  - Scaffolding of antigen receptors for immunogenic versus tolerogenic signaling.
AB  - Lymphocyte antigen receptors are responsible for inducing the opposite responses
      of immunity or tolerance. How the correct polarity of antigen receptor signaling
      is encoded has been an enduring enigma. Here we summarize recent advances
      defining key scaffolding molecules, CARMA1 (also known as CARD11) and the Cbl
      family of ubiquitin ligases, required for either immunogenic or tolerogenic
      signaling by antigen receptors. These scaffolding proteins may determine the
      polarity of response to antigen by promoting assembly around antigen receptors of
      competing multiprotein signal complexes: immunosomes versus tolerosomes. Each of
      the factors that influence immunogenicity or tolerogenicity--stage of lymphocyte
      differentiation, concurrent engagement of inhibitory or costimulatory receptors,
      extent of receptor crosslinking, and prior antigen experience--may be integrated
      in lymphocytes through their capacity to influence the probability of assembling
      immunosomes versus tolerosomes.

PMID- 14586425
TI  - Timing is everything.

PMID- 14586426
TI  - Don't create a climate of fear.

PMID- 14586427
TI  - US launches joint effort to probe dark secrets of the Universe.

PMID- 14586428
TI  - Canada prepares to pull the plug on fusion project.

PMID- 14586429
TI  - Space station light show sparks aurora riddle.

PMID- 14586430
TI  - Democrats condemn government 'meddling' with NIH.

PMID- 14586431
TI  - South Florida rocked as dean quits over political funding.

PMID- 14586432
TI  - Marine survey sees net gain in number of fish species.

PMID- 14586433
TI  - Biodiversity schemes take root in China.

PMID- 14586434
TI  - Europe kills cash flow to EURESCO science meetings.

PMID- 14586435
TI  - Doubts swirl around plan to use rigs as reefs.

PMID- 14586437
TI  - Fertilized to death.

PMID- 14586438
TI  - Restless nights, listless days.

PMID- 14586440
TI  - Middle East: a picture is worth a thousand words.

PMID- 14586439
TI  - Middle East: trying to break down the barriers.

PMID- 14586441
TI  - Timaeus's insight on the shape of the Universe.

PMID- 14586442
TI  - Chemists enthusiastic to embrace change.

PMID- 14586448
TI  - Clinical proteomics: written in blood.

PMID- 14586449
TI  - Molecular neuroscience: BAC-to-BAC images of the brain.

PMID- 14586450
TI  - Black holes: sparks of interest.

PMID- 14586451
TI  - Physiology: Foreman in the bone factory.

PMID- 14586453
TI  - Palaeontology: smart-winged pterosaurs.

PMID- 14586454
TI  - Medical technology: balancing the unbalanced.

PMID- 14586455
TI  - Neuroscience: states of mind.

PMID- 14586456
TI  - Photonics: defective quality.

PMID- 14586458
TI  - Virology: SARS virus infection of cats and ferrets.

PMID- 14586459
TI  - Palaeontology: preserved organs of Devonian harvestmen.

PMID- 14586460
TI  - A gene expression atlas of the central nervous system based on bacterial
      artificial chromosomes.
AB  - The mammalian central nervous system (CNS) contains a remarkable array of neural
      cells, each with a complex pattern of connections that together generate
      perceptions and higher brain functions. Here we describe a large-scale screen to
      create an atlas of CNS gene expression at the cellular level, and to provide a
      library of verified bacterial artificial chromosome (BAC) vectors and transgenic
      mouse lines that offer experimental access to CNS regions, cell classes and
      pathways. We illustrate the use of this atlas to derive novel insights into gene
      function in neural cells, and into principal steps of CNS development. The atlas,
      library of BAC vectors and BAC transgenic mice generated in this screen provide a
      rich resource that allows a broad array of investigations not previously
      available to the neuroscience community.

PMID- 14586462
TI  - Near-infrared flares from accreting gas around the supermassive black hole at the
      Galactic Centre.
AB  - Recent measurements of stellar orbits provide compelling evidence that the
      compact radio source Sagittarius A* (refs 4, 5) at the Galactic Centre is a 3.6
      million-solar-mass black hole. Sgr A* is remarkably faint in all wavebands other
      than the radio region, however, which challenges current theories of matter
      accretion and radiation surrounding black holes. The black hole's rotation rate
      is not known, and therefore neither is the structure of space-time around it.
      Here we report high-resolution infrared observations of Sgr A* that reveal
      'quiescent' emission and several flares. The infrared emission originates from
      within a few milliarcseconds of the black hole, and traces very energetic
      electrons or moderately hot gas within the innermost accretion region. Two flares
      exhibit a 17-minute quasi-periodic variability. If the periodicity arises from
      relativistic modulation of orbiting gas, the emission must come from just outside
      the event horizon, and the black hole must be rotating at about half of the
      maximum possible rate.

PMID- 14586461
TI  - Motor neuron columnar fate imposed by sequential phases of Hox-c activity.
AB  - The organization of neurons into columns is a prominent feature of central
      nervous system structure and function. In many regions of the central nervous
      system the grouping of neurons into columns links cell-body position to axonal
      trajectory, thus contributing to the establishment of topographic neural maps.
      This link is prominent in the developing spinal cord, where columnar sets of
      motor neurons innervate distinct targets in the periphery. We show here that
      sequential phases of Hox-c protein expression and activity control the columnar
      differentiation of spinal motor neurons. Hox expression in neural progenitors is
      established by graded fibroblast growth factor signalling and translated into a
      distinct motor neuron Hox pattern. Motor neuron columnar fate then emerges
      through cell autonomous repressor and activator functions of Hox proteins. Hox
      proteins also direct the expression of genes that establish motor topographic
      projections, thus implicating Hox proteins as critical determinants of spinal
      motor neuron identity and organization.

PMID- 14586463
TI  - Controlled collisions for multi-particle entanglement of optically trapped atoms.
AB  - Entanglement lies at the heart of quantum mechanics, and in recent years has been
      identified as an essential resource for quantum information processing and
      computation. The experimentally challenging production of highly entangled multi
      particle states is therefore important for investigating both fundamental physics
      and practical applications. Here we report the creation of highly entangled
      states of neutral atoms trapped in the periodic potential of an optical lattice.
      Controlled collisions between individual neighbouring atoms are used to realize
      an array of quantum gates, with massively parallel operation. We observe a
      coherent entangling-disentangling evolution in the many-body system, depending on
      the phase shift acquired during the collision between neighbouring atoms. Such
      dynamics are indicative of highly entangled many-body states; moreover, these are
      formed in a single operational step, independent of the size of the system.

PMID- 14586464
TI  - Demonstration of conditional gate operation using superconducting charge qubits.
AB  - Following the demonstration of coherent control of the quantum state of a
      superconducting charge qubit, a variety of qubits based on Josephson junctions
      have been implemented. Although such solid-state devices are not currently as
      advanced as microscopic qubits based on nuclear magnetic resonance and ion trap
      technologies, the potential scalability of the former systems--together with
      progress in their coherence times and read-out schemes--makes them strong
      candidates for the building block of a quantum computer. Recently, coherent
      oscillations and microwave spectroscopy of capacitively coupled superconducting
      qubits have been reported; the next challenging step towards quantum computation
      is the realization of logic gates. Here we demonstrate conditional gate operation
      using a pair of coupled superconducting charge qubits. Using a pulse technique,
      we prepare different input states and show that their amplitude can be
      transformed by controlled-NOT (C-NOT) gate operation, although the phase
      evolution during the gate operation remains to be clarified.

PMID- 14586465
TI  - High-Q photonic nanocavity in a two-dimensional photonic crystal.
AB  - Photonic cavities that strongly confine light are finding applications in many
      areas of physics and engineering, including coherent electron-photon
      interactions, ultra-small filters, low-threshold lasers, photonic chips,
      nonlinear optics and quantum information processing. Critical for these
      applications is the realization of a cavity with both high quality factor, Q, and
      small modal volume, V. The ratio Q/V determines the strength of the various
      cavity interactions, and an ultra-small cavity enables large-scale integration
      and single-mode operation for a broad range of wavelengths. However, a high-Q
      cavity of optical wavelength size is difficult to fabricate, as radiation loss
      increases in inverse proportion to cavity size. With the exception of a few
      recent theoretical studies, definitive theories and experiments for creating high
      Q nanocavities have not been extensively investigated. Here we use a silicon
      based two-dimensional photonic-crystal slab to fabricate a nanocavity with Q =
      45,000 and V = 7.0 x 10(-14) cm3; the value of Q/V is 10-100 times larger than in
      previous studies. Underlying this development is the realization that light
      should be confined gently in order to be confined strongly. Integration with
      other photonic elements is straightforward, and a large free spectral range of
      100 nm has been demonstrated.

PMID- 14586466
TI  - High interannual variability of sea ice thickness in the Arctic region.
AB  - Possible future changes in Arctic sea ice cover and thickness, and consequent
      changes in the ice-albedo feedback, represent one of the largest uncertainties in
      the prediction of future temperature rise. Knowledge of the natural variability
      of sea ice thickness is therefore critical for its representation in global
      climate models. Numerical simulations suggest that Arctic ice thickness varies
      primarily on decadal timescales owing to changes in wind and ocean stresses on
      the ice, but observations have been unable to provide a synoptic view of sea ice
      thickness, which is required to validate the model results. Here we use an eight
      year time-series of Arctic ice thickness, derived from satellite altimeter
      measurements of ice freeboard, to determine the mean thickness field and its
      variability from 65 degrees N to 81.5 degrees N. Our data reveal a high-frequency
      interannual variability in mean Arctic ice thickness that is dominated by changes
      in the amount of summer melt, rather than by changes in circulation. Our results
      suggest that a continued increase in melt season length would lead to further
      thinning of Arctic sea ice.

PMID- 14586467
TI  - Neuroanatomy of flying reptiles and implications for flight, posture and
      behaviour.
AB  - Comparison of birds and pterosaurs, the two archosaurian flyers, sheds light on
      adaptation to an aerial lifestyle. The neurological basis of control holds
      particular interest in that flight demands on sensory integration, equilibrium,
      and muscular coordination are acute. Here we compare the brain and vestibular
      apparatus in two pterosaurs based on high-resolution computed tomographic (CT)
      scans from which we constructed digital endocasts. Although general neural
      organization resembles birds, pterosaurs had smaller brains relative to body mass
      than do birds. This difference probably has more to do with phylogeny than
      flight, in that birds evolved from nonavian theropods that had already
      established trends for greater encephalization. Orientation of the osseous
      labyrinth relative to the long axis of the skull was different in these two
      pterosaur species, suggesting very different head postures and reflecting
      differing behaviours. Their enlarged semicircular canals reflect a highly refined
      organ of equilibrium, which is concordant with pterosaurs being visually based,
      aerial predators. Their enormous cerebellar floccular lobes may suggest neural
      integration of extensive sensory information from the wing, further enhancing eye
      and neck-based reflex mechanisms for stabilizing gaze.

PMID- 14586468
TI  - Spontaneously emerging cortical representations of visual attributes.
AB  - Spontaneous cortical activity--ongoing activity in the absence of intentional
      sensory input--has been studied extensively, using methods ranging from EEG
      (electroencephalography), through voltage sensitive dye imaging, down to
      recordings from single neurons. Ongoing cortical activity has been shown to play
      a critical role in development, and must also be essential for processing sensory
      perception, because it modulates stimulus-evoked activity, and is correlated with
      behaviour. Yet its role in the processing of external information and its
      relationship to internal representations of sensory attributes remains unknown.
      Using voltage sensitive dye imaging, we previously established a close link
      between ongoing activity in the visual cortex of anaesthetized cats and the
      spontaneous firing of a single neuron. Here we report that such activity
      encompasses a set of dynamically switching cortical states, many of which
      correspond closely to orientation maps. When such an orientation state emerged
      spontaneously, it spanned several hypercolumns and was often followed by a state
      corresponding to a proximal orientation. We suggest that dynamically switching
      cortical states could represent the brain's internal context, and therefore
      reflect or influence memory, perception and behaviour.

PMID- 14586469
TI  - SNARE-protein-mediated disease resistance at the plant cell wall.
AB  - Failure of pathogenic fungi to breach the plant cell wall constitutes a major
      component of immunity of non-host plant species--species outside the pathogen
      host range--and accounts for a proportion of aborted infection attempts on
      'susceptible' host plants (basal resistance). Neither form of penetration
      resistance is understood at the molecular level. We developed a screen for
      penetration (pen) mutants of Arabidopsis, which are disabled in non-host
      penetration resistance against barley powdery mildew, Blumeria graminis f. sp.
      hordei, and we isolated the PEN1 gene. We also isolated barley ROR2 (ref. 2),
      which is required for basal penetration resistance against B. g. hordei. The
      genes encode functionally homologous syntaxins, demonstrating a mechanistic link
      between non-host resistance and basal penetration resistance in monocotyledons
      and dicotyledons. We show that resistance in barley requires a SNAP-25
      (synaptosome-associated protein, molecular mass 25 kDa) homologue capable of
      forming a binary SNAP receptor (SNARE) complex with ROR2. Genetic control of
      vesicle behaviour at penetration sites, and plasma membrane location of
      PEN1/ROR2, is consistent with a proposed involvement of SNARE-complex-mediated
      exocytosis and/or homotypic vesicle fusion events in resistance. Functions
      associated with SNARE-dependent penetration resistance are dispensable for
      immunity mediated by race-specific resistance (R) genes, highlighting fundamental
      differences between these two resistance forms.

PMID- 14586470
TI  - Bone recognition mechanism of porcine osteocalcin from crystal structure.
AB  - Osteocalcin is the most abundant noncollagenous protein in bone, and its
      concentration in serum is closely linked to bone metabolism and serves as a
      biological marker for the clinical assessment of bone disease. Although its
      precise mechanism of action is unclear, osteocalcin influences bone
      mineralization, in part through its ability to bind with high affinity to the
      mineral component of bone, hydroxyapatite. In addition to binding to
      hydroxyapatite, osteocalcin functions in cell signalling and the recruitment of
      osteoclasts and osteoblasts, which have active roles in bone resorption and
      deposition, respectively. Here we present the X-ray crystal structure of porcine
      osteocalcin at 2.0 A resolution, which reveals a negatively charged protein
      surface that coordinates five calcium ions in a spatial orientation that is
      complementary to calcium ions in a hydroxyapatite crystal lattice. On the basis
      of our findings, we propose a model of osteocalcin binding to hydroxyapatite and
      draw parallels with other proteins that engage crystal lattices.

PMID- 14586473
TI  - Risky business.

PMID- 14586471
TI  - ATP-dependent reduction of cysteine-sulphinic acid by S. cerevisiae
      sulphiredoxin.
AB  - Proteins contain thiol-bearing cysteine residues that are sensitive to oxidation,
      and this may interfere with biological function either as 'damage' or in the
      context of oxidant-dependent signal transduction. Cysteine thiols oxidized to
      sulphenic acid are generally unstable, either forming a disulphide with a nearby
      thiol or being further oxidized to a stable sulphinic acid. Cysteine-sulphenic
      acids and disulphides are known to be reduced by glutathione or thioredoxin in
      biological systems, but cysteine-sulphinic acid derivatives have been viewed as
      irreversible protein modifications. Here we identify a yeast protein of relative
      molecular mass M(r) = 13,000, which we have named sulphiredoxin (identified by
      the US spelling 'sulfiredoxin', in the Saccharomyces Genome Database), that is
      conserved in higher eukaryotes and reduces cysteine-sulphinic acid in the yeast
      peroxiredoxin Tsa1. Peroxiredoxins are ubiquitous thiol-containing antioxidants
      that reduce hydroperoxides and control hydroperoxide-mediated signalling in
      mammals. The reduction reaction catalysed by sulphiredoxin requires ATP
      hydrolysis and magnesium, involving a conserved active-site cysteine residue
      which forms a transient disulphide linkage with Tsa1. We propose that reduction
      of cysteine-sulphinic acids by sulphiredoxin involves activation by
      phosphorylation followed by a thiol-mediated reduction step. Sulphiredoxin is
      important for the antioxidant function of peroxiredoxins, and is likely to be
      involved in the repair of proteins containing cysteine-sulphinic acid
      modifications, and in signalling pathways involving protein oxidation.

PMID- 14586474
TI  - Grant schemes supporting scientific entrepreneurs have induced job growth in the
      United States, but they haven't yet crossed the Atlantic, says Eugene Russo.

PMID- 14586475
TI  - Prognostic value of the rapidity of bone marrow blast cell proliferation in adult
      acute lymphoblastic leukemia.

PMID- 14586476
TI  - Stem cell plasticity revisited: CXCR4-positive cells expressing mRNA for early
      muscle, liver and neural cells 'hide out' in the bone marrow.
AB  - It has been suggested that bone marrow (BM)-derived hematopoietic stem cells
      transdifferentiate into tissue-specific stem cells (the so-called phenomenon of
      stem cell plasticity), but the possibility of committed tissue-specific stem
      cells pre-existing in BM has not been given sufficient consideration. We
      hypothesized that (i) tissue-committed stem cells circulate at a low level in the
      peripheral blood (PB) under normal steady-state conditions, maintaining a pool of
      stem cells in peripheral tissues, and their levels increase in PB during
      stress/tissue injury, and (ii) they could be chemoattracted to the BM where they
      find a supportive environment and that the SDF-1-CXCR4 axis plays a prominent
      role in the homing/retention of these cells to BM niches. We performed all
      experiments using freshly isolated cells to exclude the potential for
      'transdifferentiation' of hematopoietic stem or mesenchymal cells associated with
      in vitro culture systems. We detected mRNA for various early markers for muscle
      (Myf-5, Myo-D), neural (GFAP, nestin) and liver (CK19, fetoprotein) cells in
      circulating (adherent cell-depleted) PB mononuclear cells (MNC) and increased
      levels of expression of these markers in PB after mobilization by G-CSF (as
      measured using real-time RT-PCR). Furthermore, SDF-1 chemotaxis combined with
      real-time RT-PCR analysis revealed that (i) these early tissue-specific cells
      reside in normal murine BM, (ii) express CXCR4 on their surface and (iii) can be
      enriched (up to 60 x) after chemotaxis to an SDF-1 gradient. These cells were
      also highly enriched within purified populations of murine Sca-1(+) BM MNC as
      well as of human CD34(+)-, AC133(+)- and CXCR4-positive cells. We also found that
      the expression of mRNA for SDF-1 is upregulated in damaged heart, kidney and
      liver. Hence our data provide a new perspective on BM not only as a home for
      hematopoietic stem cells but also a 'hideout' for already differentiated CXCR4
      positive tissue-committed stem/progenitor cells that follow an SDF-1 gradient,
      could be mobilized into PB, and subsequently take part in organ/tissue
      regeneration.

PMID- 14586477
TI  - Karyotype is an independent prognostic parameter in therapy-related acute myeloid
      leukemia (t-AML): an analysis of 93 patients with t-AML in comparison to 1091
      patients with de novo AML.
AB  - The aim of this study was to compare the pattern of karyotype abnormalities of
      therapy-related acute myeloid leukemia (t-AML) (n=93) with de novo AML (n=1091),
      and to evaluate their impact on prognosis. Favorable, intermediate, and
      unfavorable cytogenetics were observed in 25.8, 28.0, and 46.2% of t-AML, and in
      22.2, 57.3, and 20.4% of de novo AML. The median overall survival (OS) was
      shorter in t-AML than in de novo AML (10 vs 15 months, P=0.0007). Favorable and
      unfavorable cytogenetics had a prognostic impact with respect to OS in both t-AML
      (P=0.001 and 0.0001) and de novo AML (P<0.0001 and <0.0001). To define the
      overall prognostic impact of cytogenetics and t-AML, a multivariate Cox's
      regression analysis was performed for OS with favorable cytogenetics, unfavorable
      cytogenetics, t-AML, age, and white blood cell (WBC) count as covariates. All
      parameters proved to be independently related to OS (P=0.001 for t-AML, P<0.0001
      for all other parameters). Within patients with t-AML, there were significant
      correlations between OS and both unfavorable (P<0.0001) and favorable
      cytogenetics (P=0.001), while age and WBC count had no impact on OS. In
      conclusion, these data indicate that cytogenetics are an important prognostic
      parameter in t-AML. Furthermore, t-AML is an unfavorable factor independent of
      cytogenetics with respect to survival.

PMID- 14586478
TI  - Infectious complications in pediatric acute myeloid leukemia: analysis of the
      prospective multi-institutional clinical trial AML-BFM 93.
AB  - Infections still remain a major cause of therapy-associated morbidity and
      mortality in children with acute myeloid leukemia (AML). To improve supportive
      care measurements, detailed information on frequency and characteristic features
      of infectious complications is needed. We retrospectively analyzed the medical
      charts of 304 children, treated in 30 hospitals according to the multi
      institutional clinical trial AML-BFM 93. Overall, 855 infectious complications
      occurred in 304 patients (fever without identifiable source (n=523; 61.2%),
      clinically (n=57; 6.7%) and microbiologically documented infections (n=275;
      32.1%)). Neutropenia was present in 74.1% of the infectious episodes. In all, 20
      patients died of infection-associated complications (15/276 (5.4%) patients
      without and 5/28 (17.9%) with Down syndrome), most of them during early induction
      therapy (n=11). Blood stream infections occurred in 228 episodes (Gram-positive
      (n=202) and Gram-negative (n=42) pathogens). Invasive fungal infection was
      probable or proven in 15 patients. In 113 out of the 855 infectious episodes
      (13.3%), pneumonia was radiologically diagnosed. Better strategies of supportive
      care might help to improve overall survival in children undergoing chemotherapy
      for AML. Therefore, children with AML should be treated in specialized pediatric
      centers, and there should be a very low threshold to readmit patients, in
      particular patients with pulmonary symptoms.

PMID- 14586479
TI  - Clinical, morphological, cytogenetic, and prognostic features of patients with
      myelodysplastic syndromes and del(5q) including band q31.
AB  - We analyzed data of 76 consecutive patients with myelodysplastic syndrome (MDS)
      and isolated del(5q) (n=66) or del(5q) plus one additional chromosomal
      abnormality (n=10) included in our MDS database over the last 26 years. The
      median age of our patient population was 66.8 years. The male to female ratio was
      1:1.7. In all, 14 patients (18%) had advanced MDS with an increased medullary
      blast count. A total of 17 patients (22%) had significant dysplasia in the
      nonmegakaryocytic cell lines. Nearly half of the study population showed
      erythroid hypoplasia in the bone marrow. The projected median survival of
      patients with isolated del(5q) is 146 months for a median follow-up of 67 months.
      Patients with an increased medullary blast count and those with an additional
      chromosomal abnormality have a significantly shorter overall survival (24 and 45
      months, respectively) than patients with isolated del(5q). We did not find
      survival differences for different cytogenetic breakpoints, nor did the amount of
      dysplasia have an impact on survival in our population. In total, 29 patients
      have died. Deaths occurred primarily due to transformation into acute leukemia,
      infection, or cardiac failure. Our data support the current definition of a
      separate entity of MDS with del(5q) that has been suggested by the World Health
      Organization.

PMID- 14586480
TI  - Successful CD34+ cell mobilization by intermediate-dose Ara-C in chronic
      lymphocytic leukemia patients treated with sequential fludarabine and Campath-1H.
AB  - Chronic lymphocytic leukemia (CLL) cells could be undetectable by flow cytometry
      or polymerase chain reaction after sequential treatment with fludarabine and
      Campath-1H. Concern has been raised regarding the ability to mobilize sufficient
      peripheral blood progenitor cells (PBPCs) for autografting after purine
      analogues, and there are few data about PBPC collection after Campath-1H. In all,
      16 CLL patients responding to sequential chemo-immunotherapy entered the study.
      In 10, mobilization regimen consisted of granulocyte colony-stimulating factor (G
      CSF) 5-10 microg/kg/die. Patients failing mobilization or not achieving the
      target of 2.5 x 10(6) CD34+ cells/kg underwent a second attempt using
      intermediate-dose (ID) Ara-C, 800 mg/m(2) every 12 h for six doses+G-CSF. PBPC
      collection after G-CSF alone was successful in two out of 10 patients. An
      adequate number of CD34+ cells were collected after ID Ara-C+G-CSF in eight
      patients failing the mobilization with G-CSF alone and in five out of six who did
      not receive G-CSF before. Greater yields of PBPCs were collected with Ara-C+G-CSF
      compared with G-CSF alone (13.8 vs 3.3). The extrahematologic toxicity was
      manageable. In conclusion, PBPC collection is feasible in CLL patients treated
      with sequential therapy including fludarabine and Campath-1H. Excellent yields
      were obtained in 92.8% of patients primed with ID Ara-C+G-CSF.

PMID- 14586481
TI  - Multiple myeloma: comparison of two dose-intensive melphalan regimens (100 vs 200
      mg/m(2)).
AB  - Several trials have shown the superior impact of high-dose melphalan (usually 200
      mg/m(2), MEL200) vs standard therapy in myeloma patients. Intermediate-dose
      melphalan (100 mg/m(2), MEL100) is also superior to the standard dose, but has
      not been clinically compared with MEL200. A total of 90 patients at diagnosis
      were treated with two MEL100 courses. Their clinical outcome was compared with
      that of a control group of 90 pair mates matched for serum beta2-microglobulin
      levels and Durie and Salmon clinical stage. These patients were treated at
      diagnosis with two MEL200 courses. Patient characteristics were similar in both
      groups except that the median age of the MEL100 group was significantly higher
      (P<0.0001). Complete remission was 35% after MEL100 and 48% after MEL200
      (P=0.08). Median event-free survival (EFS) was 32 months in the MEL100 group and
      42 months in the MEL200 group (P<0.005), but overall survival (OS) was not
      different. Transplant-related mortality was not significantly different.
      Haematological and extra-haematological toxicity was significantly reduced after
      MEL100. Despite the significant age difference, tandem MEL100 was less toxic than
      tandem MEL200, and MEL100 was inferior to MEL200 in terms of EFS but not in terms
      of OS. The intensified nonmyeloablative MEL100 regimen is an effective first-line
      treatment.

PMID- 14586482
TI  - The role of serotonergic agents as treatments for alcoholism.
AB  - Serotonergic agents remain an important area of pharmacologic study as treatments
      for alcoholism. Selective serotonin reuptake inhibitors (SSRIs) do not appear to
      be efficacious at treating a heterogeneous alcoholic group. SSRIs may, however,
      possess utility in treating later-onset alcoholics and alcoholism that is
      complicated by co-morbid major depression. The 5-HT(1A) partial agonist,
      buspirone, does not appear to be an efficacious treatment for alcoholics without
      co-morbid disease. Buspirone may, however, possess some utility in treating
      alcoholics with co-morbid anxiety disorder. Ritanserin, a 5-HT(2) antagonist,
      does not appear to be an efficacious treatment for alcoholism at
      pharmacologically relevant clinical doses. Ondansetron, a 5-HT(3) antagonist, is
      an efficacious and promising medication for the treatment of earlier-onset
      alcoholism. The differential treatment effect of SSRIs and ondansetron among
      various subtypes of alcoholics is intriguing. Future research is needed to more
      clearly understand the biopsychosocial differences that typify a particular
      alcoholic subtype. This type of understanding could develop our ability to make
      reasonable predictions as to what alcoholic subtype would respond best to a
      particular serotonergic agent, which could then be provided.

PMID- 14586483
TI  - STX-liposome conjugates as candidate vaccines.
AB  - Infection with Shiga toxin-producing (Stx) Escherichia coli (STEC) currently
      represents a serious public health problem due to its life-threatening
      complications: hemorrhagic colitis and hemolytic uremic syndrome. An inability to
      induce neutralizing antibody in response to primary STEC infection has been
      reported in STEC-infected humans. Therefore, active immunization with detoxified
      Stx to induce the production of neutralizing antibodies against Stx is currently
      an attractive option. Although this would not prevent the spread of infection, it
      would protect against death caused by cytotoxin-producing E. coli infection. Stx
      coupled with liposomes effectively induced protection against challenge with
      lethal doses of Stx in mice and in monkeys. Unique characteristics of antigen
      liposome conjugates found in our investigations are reviewed, and the possible
      application of Stx-liposome conjugates in vaccines for the prevention of life
      threatening systemic complications caused by STEC infection is discussed.

PMID- 14586484
TI  - Psychopharmacology of compulsive buying.
AB  - No standard treatment exists for the DSM-IV Impulse Control Disorders, Not
      Elsewhere Classified, including Compulsive Buying Disorder. This paper reviews
      the suggested pharmacotherapies for this disorder and their theoretical basis.
      McElroy et al. first reported benefit from antidepressant therapy in three cases
      of Compulsive Buying Disorder with comorbid depression and anxiety. In a
      retrospective chart review, McElroy's group reported on 20 patients that
      benefited from antidepressants, often in combination with mood stabilizers.
      Lejoyeux reported on two patients in whom treatment of a comorbid mood disorder
      led to remission of compulsive buying behavior. Black reported fluvoxamine to be
      effective in patients without comorbid major depression, suggesting that
      improvement was independent of the treatment of mood symptoms. Kim reported
      improvement with naltrexone, an opioid antagonist, in a case series. Two double
      blind placebo-controlled trials found fluvoxamine no better than placebo;
      however, in both studies patients kept shopping logs, which may have confounded
      the results. An open-label trial of citalopram and a double-blind crossover trial
      which excluded shopping logs both reported positive results. Twelve-month follow
      up data for the open-label group found that remission rates at quarterly time
      points were independent of continuing drug therapy. The data reviewed above
      suggest that pharmacologic interventions may be effective for compulsive buying
      disorder. Whether pharmacological treatment is superior to placebo and whether it
      is more, less or equally effective compared to psychotherapeutic interventions
      remains to be established.

PMID- 14586485
TI  - Strategies for tumor immune escape.
AB  - The interactions between the immune system and malignant cells play an important
      role in tumorigenesis. Evidence that tumors are immunogenic continues to
      accumulate. Although they frequently express antigens in a form recognizable by
      the host immune system, tumors commonly "escape" the immune response. Tumors may
      therefore progress by evolving variants that can evade immune responses or by
      developing other strategies to avoid immune control. The purpose of this review
      is to evaluate the current status of knowledge concerning these different tumor
      escape strategies.

PMID- 14586486
TI  - Epilepsy genetics.
AB  - Genetics have for a long time been suspected of playing an important role in
      idiopathic generalized epilepsy. The last decade has seen the discovery of
      several genes underlying epilepsy transmitted in a Mendelian fashion. Among these
      are genes causing recessive neurodevelopmental disorders complicated by seizures.
      In addition, several genes, mainly coding for ion channels, have been identified
      in rare families exhibiting a wide variety of idiopathic epilepsy phenotypes. The
      next decade will likely reveal whether these or related genes also act as
      susceptibility factors for sporadic epilepsy.

PMID- 14586487
TI  - Cycling chemotherapy: a promising approach to reducing the morbidity and
      mortality of nosocomial infections.
AB  - In the past several decades, nosocomial infections have emerged as one of the
      most serious contributors to hospital morbidity and mortality, particularly
      amongst patients who require intensive care. Resistant organisms, both Gram
      negative and Gram-positive, are now to blame for a significant portion of
      hospital-acquired infections. Efforts to prevent nosocomial infection had
      historically focused on infection control measures, such as patient isolation.
      However, there have been numerous reports of the increasing prevalence of
      antibiotic resistance, as well as the dramatic, negative impact of the infections
      they cause, both in terms of patient outcomes and attributable costs, demanding
      new methods to halt this growing epidemic. The increasing threat of resistance
      may be attributed in part to the widespread and increasingly inappropriate use of
      antimicrobials, which inadvertently exert sufficient effect on the hospital (and
      now community) environment to allow the preferential selection of resistant
      microbes. This idea of selective antibiotic pressure is supported by data showing
      volume of antibiotic use and inadequate antimicrobial coverage as risk factors
      for increased morbidity and mortality. Accordingly, the focus of nosocomial
      infection control has now largely shifted towards the judicious use of antibiotic
      therapy. There have been numerous attempts to curtail antibiotic usage through
      various forms of antibiotic stewardship: formulary restriction, computerized
      decision-support and abbreviated course empiric therapy. Aside from the inherent
      difficulty of effecting change in physician practice, we are burdened,
      particularly in the setting of empiric therapy, with the need to balance between
      adequate therapy for the individual and prudent drug selection so as not to
      endanger other patients in the environment through resistant organism selection.
      Cycling chemotherapy for empiric treatment of suspected infection is a method
      uniquely designed to address these challenges.

PMID- 14586488
TI  - Hamstring weakness as an indicator of poor knee function in ACL-deficient
      patients.
AB  - Anterior cruciate ligament (ACL) rupture causes instability to the knee joint
      which leads each patient to a different degree of disability. The purpose of this
      study was to examine the strength of the quadriceps and the hamstrings in ACL
      deficient amateur soccer players at different levels of functional status. Thirty
      male amateur soccer players were separated into three groups according to their
      Lysholm score; the high-L1 (Lysholm > or =84), the intermediate-L2 (84> Lysholm >
      or =72) and the low-L3 (Lysholm <72) knee function groups. The control group
      consisted of 12 amateur soccer players. The strength of the quadriceps and
      hamstrings was assessed isokinetically at 60 degrees/s. The quadriceps
      demonstrated significant deficits of the injured knee compared to the intact knee
      in all groups, whilst the hamstrings showed significant weakness only in the low
      function group. Respective percentage deficits in groups L1, L2 and L3 were
      13.7%, 16.0% and 18.6% for the quadriceps and 2.4%, 5.6% and 19.2% for the
      hamstrings. All groups had significant quadriceps weakness which did not differ
      between the groups. In contrast, the strength deficit of the hamstrings was an
      indicator of poor knee function, since they were significantly weak only in group
      L3, which represented patients who clearly failed to compensate for instability
      symptoms. In groups L1 and L2 the side-to-side differences were within the area
      of asymmetry measured in the control group. Clinical importance of the results is
      discussed.

PMID- 14586489
TI  - The meniscus Arrow or metal screw for treatment of osteochondritis dissecans? In
      vitro comparison of their effectiveness.
AB  - Three draw bench tests in axial direction were conducted of the pull out forces
      in predrilled human condylar bone of one single meniscus Arrow, one single metal
      screw, and three Meniscus Arrows in one bone block, the Arrows being inserted
      using the standard hand instruments. Bone blocks with three meniscus Arrows were
      tested additionally in tangential direction, imitating shear forces. All observed
      values were within the range of 1 standard error (SE) or higher and exceeded the
      values in meniscal tissue as reported in the literature. These are much higher
      than the shear force during a single movement in the human knee. Most metallic
      devices used for fixation of the fragments in the treatment of osteochondritis
      dissecans must be removed in a second operation. Left in place, as with the
      Herbert screws, they can disturb future imaging and damage the opposite cartilage
      of the tibia plateau. Staples left in place can break. Finally, some metals evoke
      allergic reactions and, at least in animals, are potent carcinogens. Although
      fusion of osteochondritis dissecans fragments in their original locations fixed
      with noncompressive biodegradable pins has been reported, these tests show the
      hold of compressive meniscus Arrows in bone to contribute to a better result than
      noncompressive pins. Other biodegradable devices are also available for this
      application. However, one advantage is that using meniscus Arrows, already
      available in the hospital for mending ruptured menisci, saves the costs of
      investing in other sets of instruments and devices. Another advantage is the
      smaller diameter of the meniscus Arrows than that of other biodegradable devices,
      resulting in less damage to the fragments.

PMID- 14586490
TI  - Age-related changes in human PCLs: a light and electron microscopic study.
AB  - No studies have previously compared ultrastructural differences in human
      posterior cruciate ligaments in different age groups, but such differences may be
      of importance in the reconstruction of this ligament. We used light and
      transmission electron microscopy to compare ultrastructural differences in the
      posterior cruciate ligaments of 36 patients by age and sex. We found no
      differences between the sexes or in the groups aged between 30 and 59 years.
      However, collagen fibers with variable diameters were observed in those aged 10
      19 years, with many oxytalan fibers between the collagen fibers. We also found a
      decrease in collagen fiber diameter and increase in collagen fibril concentration
      with aging, with a maximum increase in collagen fibril concentration in those
      aged 60-69 years.

PMID- 14586491
TI  - Gait patterns before and after anterior cruciate ligament reconstruction.
AB  - The aim of this study is to determine how selected gait parameters may change as
      a result of anterior cruciate ligament (ACL) deficiency and following ACL
      reconstruction. The study was performed on 25 ACL-deficient subjects prior to and
      6 weeks, 4 months, 8 months and 12 months after ACL reconstructive surgery by the
      bone-patellar tendon-bone technique. Gait analysis was performed using the zebris
      three-dimensional ultrasound-based system with surface electromyograph (zebris
      Medizintechnik GmbH, Germany). Kinematic data were recorded for the lower limb.
      The muscles examined include vastus lateralis and medialis, biceps femoris and
      adductor longus. The results obtained from the injured subjects were compared
      with those of 51 individuals without ACL damage. The acute ACL-deficient patients
      exhibited a quadriceps avoidance pattern prior to and 6 weeks after surgery. The
      quadriceps avoidance phenomenon does not develop in chronic ACL-deficient
      patients. In the individuals operated on, the spatial-temporal parameters and the
      knee angle had already regained a normal pattern for the ACL-deficient limb
      during gait 4 months after surgery. However, the relative ACL movement parameter
      which describes the tibial translation into the direction of ACL-and the EMG
      traces show no significant statistical difference compared with the values of
      healthy control group just 8 months after surgery. The results suggest that: (1)
      development of a quadriceps avoidance pattern is less common than previously
      reported, (2) anterior cruciate ligament deficiency and reconstruction
      significantly alter the lower extremity gait pattern, (3) the gait parameters
      shift towards the normal value pattern, and (4) the re-establishment of pre
      injury gait patterns--including the normal biphase of muscles--takes at least 8
      months to occur.

PMID- 14586492
TI  - Fixation strength of three different graft types used in posterior cruciate
      ligament reconstruction.
AB  - Surgical reconstruction is generally recommended for PCL and associated ligament
      injuries. A variety of graft choices exist for PCL reconstruction surgery. This
      study evaluated the initial fixation strength of three grafts using in PCL
      reconstruction in a porcine model. Twenty fresh porcine knees were harvested and
      randomly assigned to four groups: bone-patellar tendon-bone graft, quadruple
      tendons graft, Achilles tendon graft, and normal PCL. After reconstruction the
      knee was tested on an MTS testing machine by translating the tibia posteriorly
      until failure at 30 degrees of flexion, neutral rotation, and anatomical vertical
      alignment. Biomechanical parameters including maximal failure load, stiffness,
      and failure modes, were analyzed and compared. In the maximal failure load, the
      four-strand tendon group was significantly greater than the other two grafts.
      However, it had greatest translation. There were no significant differences
      between the three grafts in stiffness. All three of these commonly used grafts
      had weaker initial fixation strength and stiffness than normal PCL. Graft failure
      occurred mainly at the tendon-bone junction and tendon-suture sites. The Patellar
      tendon group had significantly least translation during continuing loading.

PMID- 14586493
TI  - Neurochemical monitoring using intracerebral microdialysis during cardiac
      resuscitation.
AB  - OBJECTIVE: After cardiac resuscitation, hypoxic encephalopathy often is the
      limiting factor regarding outcome due to the oxygen sensitivity of the brain.
      Intracerebral microdialysis is a highly sensitive technique to monitor cerebral
      energy metabolism and for the early detection of cerebral hypoxia. PATIENT AND
      INTERVENTIONS: A 34-year-old male patient who had to be craniectomized due to a
      mass demanding middle cerebral artery infarct. A microdialysis catheter was
      inserted into the left frontal lobe and, as control, into the abdominal
      subcutaneous adipose tissue. Pulmonary embolism and asystolia leading to cardiac
      resuscitation occurred. MEASUREMENTS AND RESULTS: The cerebral chemical markers
      of energy metabolism glucose, lactate, pyruvate, and the marker of cell membrane
      damage glycerol were measured. Except for subcutaneous glucose, all markers
      showed a sudden and significant increase during resuscitation and a prolonged
      period afterwards. After some hours all values returned to normal. CONCLUSION:
      This is the first reported case of monitoring neurochemical markers using
      intracerebral microdialysis during cardiac resuscitation. The findings indicate
      the importance of early and efficient resuscitation and demonstrate that
      deviations in cerebral energy metabolism are reversible.

PMID- 14586494
TI  - Pharmacokinetics and pharmacodynamics of dopamine and norepinephrine in
      critically ill head-injured patients.
AB  - OBJECTIVE: To explore the pharmacokinetics and pharmacodynamics of dopamine and
      norepinephrine. DESIGN: Prospective, controlled, trial. SETTING: Neurosciences
      critical care unit. PATIENTS: Eight patients with a head injury, requiring
      dopamine or norepinephrine infusions to support cerebral perfusion pressure
      (CPP). INTERVENTION: Patients received in randomised order, either dopamine or
      norepinephrine to achieve and maintain a CPP of 70 mmHg, and then, following a 30
      min period of stable haemodynamics, a CPP of 90 mmHg. Data were then acquired
      using the second agent. Haemodynamic measurements were made during each period
      and a blood sample was obtained at the end of each study period for analysis of
      plasma catecholamine concentrations MEASUREMENTS AND RESULTS: Plasma levels of
      norepinephrine and dopamine were significantly related to infusion rates but did
      not have a simple linear relationship to haemodynamic parameters. However, there
      was a significant quadratic relationship between the infusion rate of dopamine
      and cardiac index (r2=0.431), and systemic vascular resistance index (r2=0.605),
      with a breakpoint (at which cardiac index reduced and SVRI increased) at a
      dopamine plasma level of approximately 50 nM/l (corresponding to an infusion rate
      of approximately 15 microg.kg(-1).min(-1)). CONCLUSIONS: Norepinephrine and
      dopamine have predictable pharmacokinetics; however, those of dopamine do not fit
      a simple first-order kinetic model. The pharmacodynamic effects of dopamine and
      norepinephrine show much inter-individual variability and unpredictability.
      Plasma levels of dopamine appear to relate to variations in adrenergic receptor
      effects with break points that reflect expectations from infusion-rate related
      pharmacodynamics.

PMID- 14586495
TI  - Pulmonary capillary pressures during the acute respiratory distress syndrome.
AB  - OBJECTIVES: (1). To describe the evolution of pulmonary capillary pressure (Pcap)
      and of the pressure drop across the pulmonary venous bed from early to
      established acute respiratory distress syndrome (ARDS), (2). to assess Pcap under
      different levels of positive end-expiratory pressure (PEEP) and (3). to compare
      the visual method and a mathematical model to determine Pcap. DESIGN:
      Prospective, intervention study. SETTING: Intensive care unit in a teaching
      institution. PATIENTS: Nine ARDS patients, according to the ARDS Consensus
      Conference criteria. INTERVENTIONS: Pulmonary arterial pressures were measured
      during routine respiratory mechanics measurements throughout ARDS. Four PEEP
      levels (6, 9, 12 and 15 cmH(2)O) were studied. MEASUREMENTS AND RESULTS:
      Pulmonary artery occlusions were made in triplicate at each PEEP level. Pcap was
      determined for every occlusion trace by three observers (visual method) and a
      mathematical model. Diastolic pulmonary artery pressure (PAPd) and pulmonary
      artery occlusion pressure (PAOP) were measured. The visually determined Pcap
      showed a bias of 2.5+/-2.1 mmHg as compared to the mathematical estimation. PAPd,
      Pcap and PAOP tended to decrease from early to late ARDS ( p=0.128, 0.265,
      0.121). Pcap-PAOP (6.3+/-2.7 mmHg) did not change throughout ARDS. Higher PEEP
      levels were associated with increased PAPd, Pcap and PAOP, as well as with larger
      Pcap-PAOP throughout ARDS. CONCLUSIONS: Pulmonary capillary pressure cannot be
      predicted from PAOP during early and established ARDS. The high variability in
      Pcap-PAOP increases the risk for underestimation of filtration pressures and
      consequently the risk for lung edema. Pcap can be estimated at the bedside by
      either the visual or mathematical methods.

PMID- 14586498
TI  - Comment on: "Hemodynamic response to coupled plasmafiltration-adsorption in human
      septic shock" by Formica et al.

PMID- 14586496
TI  - Effects of C1 esterase inhibitor administration on intestinal functional
      capillary density, leukocyte adherence and mesenteric plasma extravasation during
      experimental endotoxemia.
AB  - OBJECTIVE: To determine the effects of C1 esterase inhibitor (C1-INH)
      administration on intestinal functional capillary density, leukocyte adherence,
      and mesenteric plasma extravasation during experimental endotoxemia. DESIGN AND
      SETTING: Prospective, randomized, controlled animal study in the experimental
      laboratory of a university. SUBJECTS: 42 male Wistar rats. INTERVENTIONS: The
      animals were divided into three groups. One half of the animals of each group
      underwent studies of intestinal functional capillary density and leukocyte
      adherence on venular endothelium by intravital fluorescence microscopy. In the
      other half of the animals mesenteric plasma extravasation (FITC albumin) was
      determined by intravital fluorescence microscopy. Treatment groups received
      endotoxin infusion of 2.5 mg/kg per hour (group 2 and 3) and 100 U/kg b.w. C1-INH
      (group 3) during the 2 h of endotoxemia. MEASUREMENTS AND RESULTS: Endotoxemia
      resulted in a significant decrease in mucosal functional capillary density (18.5%
      vs. controls), which was reduced by C1-INH administration (9.5%). Treatment with
      C1-INH also significantly attenuated intestinal leukocyte adherence in submucosal
      venules (35% vs. endotoxin group) and mesenteric plasma extravasation (44% vs.
      endotoxin group). CONCLUSIONS: C1-INH administration diminishes endotoxin-induced
      changes in the intestinal microcirculation during experimental endotoxemia.

PMID- 14586499
TI  - Proinsulin C-peptide increases nitric oxide production by enhancing mitogen
      activated protein-kinase-dependent transcription of endothelial nitric oxide
      synthase in aortic endothelial cells of Wistar rats.
AB  - AIMS/HYPOTHESIS: Recent studies have suggested that proinsulin C-peptide improves
      vascular functions, possibly through nitric oxide (NO) production. To clarify the
      molecular mechanisms of vascular NO production induced by C-peptide, we examined
      the effects of C-peptide on NO production and NO synthase expression in rat
      aortic endothelial cells in connection with mitogen-activated protein kinase
      (MAPK) activation. METHODS: Aortic endothelial cells were isolated from female
      Wistar rats, cultured to confluence, and serum-starved for 24 h before treatment
      with C-peptide. Nitric oxide production was measured by the DAF-2 fluorescence
      dye method and relative amounts of endothelial nitric oxide synthase (eNOS)
      protein and its mRNA were semi-quantified by western blot and RT-PCR analyses
      respectively. Activation of MAPK was estimated by western blot detection of
      activity-related phosphorylation and in vitro kinase assay. RESULTS: Stimulation
      of cells with C-peptide for 3 h doubled NO production, which was suppressed by
      the NO synthase inhibitor, N(G)-nitro- L-arginine methyl ester (L-NAME).
      Stimulation also increased mRNA and protein contents of eNOS in a manner
      sensitive to the transcription inhibitor actinomycin D. It did not affect
      inducible NO synthase mRNA. C-peptide also induced rapid phosphorylation and
      activation of extracellular signal-regulated kinase (ERK, also known as
      p44/42MAPK), but not of p38MAPK. In cells pretreated with the ERK inhibitor
      PD98059 the C-peptide-elicited increase of NO production and eNOS was abrogated
      in a dose-dependent manner; suppression of ERK phosphorylation induced by C
      peptide also occurred. CONCLUSIONS/INTERPRETATION: Our results show that C
      peptide increases NO production by increasing eNOS protein contents through ERK
      dependent up-regulation of eNOS gene transcription. This could explain some
      actions of C-peptide on the vasculature, indicating a pivotal role for C-peptide
      in vascular homeostasis.

PMID- 14586500
TI  - "The relative contributions of insulin resistance and beta-cell dysfunction to
      the pathophysiology of Type 2 diabetes", by Kahn SE.

PMID- 14586502
TI  - -to: Shafrir E, Raz I (2003) For debate. Diabetes: mellitus or lipidus?
      Diabetologia 46: 433-440.

PMID- 14586503
TI  - Inheritance of plant regeneration from maize (Zea mays L.) shoot meristem
      cultures derived from germinated seeds and the identification of associated RAPD
      and SSR markers.
AB  - The inheritance of shoot regeneration through shoot-tip meristem culture derived
      from maize seedling was evaluated, and the markers (RAPD and SSR) associated with
      this regeneration character were identified both in a group of North American
      maize inbreds and a crossing population. A discrete distribution of percent
      regeneration and no. of shoots per explant was observed in the inbred group and
      the F(2) population. The results suggested that this regenerable trait was
      controlled by several major genes. Five RAPD markers were identified to be
      relevant to percent regeneration in maize shoot-tip culture system. One RAPD
      marker and three SSR markers were associated with no. of shoot per explant and
      its relevant traits. Of them marker BC603-1600 explained 18% of the variation for
      no. of shoot per explant and 16% of the variation for callus size. The BC603-1600
      was sequenced and assigned in linkage group 7 based on a NCBI blast search. The
      information provided here should benefit to determine the genetic mechanisms
      involved in the maize regeneration response related to shoot meristem culture
      pathway and benefit to select high regenerable germplasm by using marker assisted
      selection.

PMID- 14586504
TI  - Fine mapping of three quantitative trait loci for late blight resistance in
      tomato using near isogenic lines (NILs) and sub-NILs.
AB  - An earlier study identified quantitative trait loci (QTLs) lb4, lb5b, and lb11b
      for quantitative resistance to Phytophthora infestans (late blight) in a
      backcross population derived from crossing susceptible cultivated tomato (
      Lycopersicon esculentum) with resistant L. hirsutum. The QTLs were located in
      intervals spanning 28-47 cM. Subsequently, near-isogenic lines (NILs) were
      developed for lb4, lb5b, and lb11b by marker-assisted backcrossing to L.
      esculentum. Sub-NILs containing overlapping L. hirsutum segments across each QTL
      region were selected and used to validate the QTL effects, fine-map QTLs, and
      evaluate potential linkage drag between resistance QTLs and QTLs for
      horticultural traits. The NILs and sub-NILs were evaluated for disease resistance
      and eight horticultural traits at three field locations. Resistance QTLs were
      detected in all three sets of NIL lines, confirming the BC(1) mapping results.
      Lb4 mapped near TG609, and between TG182 and CT194, on chromosome 4, a 6.9-cM
      interval; lb5b mapped to an 8.8-cM interval between TG69a and TG413 on chromosome
      5, with the most likely position near TG23; and lb11b mapped to a 15.1-cM
      interval on chromosome 11 between TG194 and TG400, with the peak centered between
      CT182 and TG147. Most QTLs for horticultural traits were identified in intervals
      adjacent to those containing the late blight resistance QTLs. Fine mapping of
      these QTLs permits the use of marker-assisted selection for the precise
      introgression of L. hirsutum segments containing late blight resistance alleles
      separately from those containing deleterious alleles at horticulturally important
      QTLs.

PMID- 14586505
TI  - A likelihood approach for mapping growth trajectories using dominant markers in a
      phase-unknown full-sib family.
AB  - Dominant markers have been commonly used in mapping quantitative trait loci
      (QTLs) in outcrossing species, in which not much prior genome information is
      available. But the dominant nature of these markers may lead to reduced QTL
      mapping precision and power. A new statistical method is proposed to incorporate
      growth laws into a QTL mapping framework, under which the use of the efficiency
      of dominant markers can be increased. This new method can be used to identify
      specific QTLs affecting differentiation in growth trajectories, and further
      estimate the timing of a QTL to turn on, or turn off, affecting growth during the
      entire ontogeny of a species. Using this method based on dominant markers we have
      successfully mapped a QTL for stem height growth trajectories to a linkage group
      in a forest tree. The implications of this method for the understanding of the
      genetic architecture of growth using dominant markers are discussed.

PMID- 14586506
TI  - Characterization of genetic variation in and phylogenetic relationships among
      diploid Aegilops species by AFLP: incongruity of chloroplast and nuclear data.
AB  - Intra- and inter-specific genetic variation was investigated in seven diploid
      Aegilops species using the amplified fragment length polymorphism (AFLP)
      technique. Of the seven species, the cross-pollinating Aegilops speltoides and
      Aegilops mutica showed high levels of intraspecific variation whereas the
      remaining five self-pollinating species showed low levels. Aegilops bicornis,
      Aegilops searsii and Ae. speltoides formed one cluster in the dendrograms, while
      Aegilops caudata and Aegilops umbellulata formed another. Relationships among the
      species inferred were more consistent with the relationships inferred from
      studies of chromosome pairing in interspecific hybrids, and previous molecular
      phylogenetic reconstructions based on nuclear DNA, than they were with those
      based on molecular plasmon analysis, suggesting that the nuclear genome has
      evolved differently from the cytoplasmic genome in the genus Aegilops.

PMID- 14586507
TI  - Targeted mapping of a sugarcane rust resistance gene (Bru1) using bulked
      segregant analysis and AFLP markers.
AB  - The presence of a major resistance gene (Bru1) for brown rust in the sugarcane
      cultivar R570 (2n about 115) was confirmed by analyzing segregation of rust
      resistance in a large population of 658 individuals, derived from selfing of
      clone R570. A subset of this population was analyzed with AFLP and bulked
      segregant analysis (BSA) to develop a detailed genetic map around the resistance
      gene. Four hundred and forty three primer pairs were used resulting in the
      identification of eight AFLP markers surrounding the resistance gene in an
      interval of 10 cM, with the closest markers located at 1.9 and 2.2 cM on each
      side of the gene. Efficiency of the AFLP/BSA applied to the complex polyploid
      genome of sugarcane is discussed, as well as the potential of the newly
      identified AFLP markers for developing a map-based cloning approach exploiting,
      synteny conservation with sorghum.

PMID- 14586501
TI  - Dissecting autoimmune diabetes through genetic manipulation of non-obese diabetic
      mice.
AB  - Type 1 diabetes results from a genetically and immunologically complex autoimmune
      process that is specifically directed against the pancreatic beta cells. Non
      obese diabetic mice spontaneously develop a form of autoimmune diabetes closely
      resembling the disease in humans. This happens because, like human diabetic
      patients, non-obese diabetic mice have an unfortunate combination of apparently
      normal alleles at numerous loci associated with Type 1 diabetes. In isolation,
      each of these allelic variants affords a small degree of susceptibility to
      diabetes. In combination, however, they set in motion a series of immunological
      events that lead to islet inflammation and overt diabetes. Type 1 diabetes is
      associated with defects in self-tolerance and immunoregulation. It involves
      presentation of beta cell antigens to autoreactive T lymphocytes by professional
      antigen-presenting cells, the recruitment of antigen-activated T cells into
      pancreatic islets, and the differentiation of these antigen-activated lymphocytes
      into beta cell killers. Understanding the precise sequence of events in the
      pathogenesis of Type 1 diabetes has been, and remains, a challenging task. Much
      of our understanding of the immunology of the disease stems from studies of
      genetically engineered, non-obese diabetic mice. These mice provide reductionist
      systems, with which the contribution of individual cellular elements, molecules
      or genes to the disease process can be dissected. This review focuses on the
      lessons that have been learned through studies of these mice.

PMID- 14586508
TI  - [No influence of urinary nitrate excretion on the goitre prevalence in Germany].
AB  - BACKGROUND: It has long been known that nitrate combined with iodiduria < 100
      micro gI(-)/l has a goitrogenic effect. The cause is a partial blockage of the
      sodium- iodide symporter together with a hindrance to iodide absorption in the
      intestine. 90% of the intake of nitrate is excreted in urine. Therefore
      nitraturia provides information about the population. The rare epidemiological
      studies of the influence of NO(3)(-) on goitre are limited to a small selection
      of older, regional samples. Our aim was to investigate the role of nitrate in the
      occurrence of goitre in Germany. METHODS: Using random samples from 3,059
      clinically healthy persons of both sexes between 18 and 70 years old from all
      over Germany, we examined nitraturia and the prevalence of goitre or nodules,
      including the corresponding iodiduria. (Sonography: 7.5 MHz linear transducer;
      nitrate determination: isocratic ion chromatography; iodide determination: cerium
      arsenite method.) Both the NO(3)(-) and the iodide excretion in spontaneous urine
      were measured in relation to 1 g creatinine. Statistical processing: Mann-Whitney
      U-Test, correlation analysis, multivariate linear regression analysis. RESULTS:
      Median for nitraturia: 55.2 mg NO(3)(-)/g creatinine (men 61.5, women 51.5; p <
      0.03). Significant increase in regional nitrate excretion from North to South and
      from East to West. No statistical connection between nitraturia, thyroid size and
      nodules. In the multivariate linear regression analysis relating to thyroid
      size/focal lesions, NO(3)(-) played the smallest part among the variables age,
      gender, body mass index, iodiduria, nitraturia. In the case of iodiduria with <
      50 micro g I(-)/g creatinine (n = 71), there was a correlation between nitraturia
      and thyroid size (r = 0.18; p < 0.05). All persons with a nitraturia of > 60 mg
      NO(3)(-)/g creatinine (n = 1,166) evidenced a correlation with the thyroid size
      (r = 0.18; p < 0.01). CONCLUSION: Since alimentary iodine shortage in Germany has
      been overcome to a large extent (iodiduria 100-200 micro gI(-)/l) and the nitrate
      content lies clearly below the WHO limit, the goitrogenic effect of nitrate is
      only of individual and not of epidemiological importance. The slight regional
      differences in NO(3)(-) excretion are the consequence of the nitrate content in
      drinking water and have no effect on the thyroid gland.

PMID- 14586509
TI  - [Fixed Combination of a Long-Acting beta(2)-Agonist and an Inhaled Steroid. A
      Therapeutic Option for COPD?].
AB  - BACKGROUND: The introduction of long-acting bronchodilators (beta(2)-agonists and
      anticholinergics) has essentially changed the therapy of chronic obstructive
      pulmonary disease (COPD) in the last years. Furthermore, the understanding of the
      pathophysiology of the disease has improved, leading to a reevaluation of
      essential therapeutic principles. Especially, the significance of inhaled
      steroids in elder and sicker patients is now being acknowledged. COMBINED
      TREATMENT OF COPD: For a long time, the use of the fixed combination of an
      inhaled steroid and a long-acting beta(2)-agonist seemed to be reserved for the
      therapy of bronchial asthma, as there was clinical as well as pharmacologic
      evidence of a synergism of the therapy components, i. e., increase in beta(2)
      receptor density and responsiveness by the steroid and activation of the
      glucocorticoid receptor by the beta(2)-agonist. However, first studies in COPD
      showed significant, clinically relevant improvement of the classic outcome
      parameter pulmonary function as well as of symptoms, especially dyspnea, quality
      of life and incidence of severe exacerbations, exceeding solely additive effects
      of the monosubstances. CONCLUSION: According to clinical data, the supposed
      synergism is very likely, even though pharmacodynamic evidence is not yet
      available. However, the beneficial effect of combination therapy could be
      demonstrated for older patients with more severe disease (FEV(1) < 50%, history
      of frequent exacerbations) only. Further studies will be needed to clarify, if
      other patient groups will benefit from this therapy option and which dosage is to
      be regarded as optimal.

PMID- 14586510
TI  - [Brain natriuretic Peptide. Diagnostic and prognostic value in chronic heart
      failure].
AB  - Brain natriuretic peptide (BNP) has been established as a new and reliable
      laboratory marker for chronic heart failure (CHF). BNP is a neurohormone secreted
      by the cardiac ventricles in response to volume expansion and pressure overload.
      It is released as N-terminal pro-brain natriuretic peptide and then
      Korrelaenzymatically cleaved into the NT fragment and the immunoreactive BNP. BNP
      promotes vasodilatation, natriuresis, diuresis, and inhibits the renin
      angiotensin- aldosterone system. BNP values depend on sex, age, renal function,
      and the assay used. BNP exhibits a high sensitivity and specificity for the
      diagnosis of CHF. BNP determination improves the differential diagnosis of acute
      dyspnea. Normal BNP levels are found, if dyspnea is caused by pulmonary disease,
      pathologic BNP values are typical of a cardiac disorder. In CHF, BNP levels can
      be used as a reliable independent predictor of cardiac death or deterioration of
      cardiac functional status at follow-up. As a general screening test for CHF, BNP
      is of limited value due to a substantial number of false positive test results,
      which lead to further cardiac diagnostic testing. BNP is helpful for the
      assessment of the success of CHF therapy in acute cardiac decompensation and
      outpatients. An individually tailored CHF therapy with serial determination of
      BNP opens up new perspectives for a more objective and effective treatment of CHF
      patients.

PMID- 14586511
TI  - [Managing the obese patient].

PMID- 14586512
TI  - [Self-Management of Anti-Obstructive Therapy for Severe COPD with a Subcutaneous
      Terbutaline Pump].
AB  - BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) may be
      difficult to stabilize with standard inhaled and oral medication. In those cases,
      outpatient care may even be impossible. Alternative therapeutic strategies, like
      subcutaneous self-application of terbutaline, could help to further improve
      health status. CASE REPORT: A 42-year old patient with severe COPD was admitted
      to the hospital. Despite maximal anti-obstructive therapy he required additional
      intravenous relief therapy and discharge was not possible. We treated this
      patient with a subcutaneous terbutaline pump for continuous and demand
      medication. We could show a significant decrease in additional intravenous
      medication, and the patient could leave the hospital. CONCLUSION: The use of
      terbutaline applied by a subcutaneous pump in addition to standard therapy may be
      helpful in severely ill patients suffering from COPD. This measure increased
      quality of life and shortened hospital stay.

PMID- 14586513
TI  - [Differential Diagnosis Macro CK Type 1 in Thoracic Pain Syndrome and Increased
      CK-MB].
AB  - BACKGROUND: Macro CK (creatine kinase) as a reason for high CK values has been
      known since 1979. Even in the era of troponin determination for the diagnosis of
      myocardial infarction, an elevated CK value can still cause confusion, especially
      as CK-MB rises earlier than troponin. The case report should remind us of this
      often forgotten differential diagnosis of elevated CK. CASE REPORT: A 73-year-old
      patient was treated with leuprorelin hormone therapy for prostate cancer (stage
      pT1c G2). In addition, he received percutaneous radiation therapy of the prostate
      and high-dose-rate brachytherapy twice with 10 Gy each. Close to 1 year later, he
      complained for the first time of dyspnea on exertion and thoracic tightness.
      Serum CK was 232 U/l, and CK-MB 62 U/l, which was confirmed by several controls.
      Troponin T test was negative, and GOT, GPT, LDH, and PSA were all within the
      normal range. Acute myocardial infarction was ruled out on clinical grounds and
      by six sequential ECGs. Subsequently, the patient remained without further
      cardiac complaints and in good condition. Isoenzyme electrophoresis finally
      solved the problem and revealed CK-BB-IgG complex type 1 (macro CK-1).
      CONCLUSION: High CK-MB values in cardially healthy patients should remind us of
      the possibility of macro CK which is seen in approximately 0.5% of cases and
      should be included in the differential diagnosis.

PMID- 14586514
TI  - [Prekallikrein (Fletcher Factor) Deficiency and Prolongation of APTT Reaction].
AB  - BACKGROUND: Prekallikrein (Fletcher factor) is a protein of the contact phase of
      the blood coagulation system. A deficiency is a very rare event. The clinical
      meaning is still unknown. CASE REPORT: In a 24-year-old patient of Croatian
      nationality, who has never suffered from any kind of proneness to hemorrhage, a
      considerable prolongation of activated partial thromboplastin time (APTT) was
      diagnosed preoperatively. The prothrombin time (PT) was normal. The patient had
      to be subjected to horseshoe-kidney surgery. CLOTTING TESTS: A very seldom
      Fletcher factor (prekallikrein) deficiency type II was detected. The activity was
      < 1%, but the prekallikrein concentration was normal, comparable to that in
      normal plasma. THERAPY AND COURSE: Complications were neither noticed during
      renal surgery nor postoperatively. The patient did not show clinical symptoms.
      This fact corroborates reports about similar cases published earlier. CONCLUSION:
      Nevertheless, attention has to be paid to these exceptionally rare symptoms, as
      in some publications, thromboembolic or even bleeding complications were
      reported.

PMID- 14586515
TI  - [Recurrent spinal transverse symptoms in a patient with idiopathic
      myelofibrosis].

PMID- 14586516
TI  - [Information technology in medicine].

PMID- 14586517
TI  - [E-learning in medical education, graduate and continuing medical education.
      Status and prospects].

PMID- 14586518
TI  - Time-resolved evanescent wave-induced fluorescence anisotropy for the
      determination of molecular conformational changes of proteins at an interface.
AB  - We have shown that the molecular conformation of a protein at an interface can be
      probed spatially using time-resolved evanescent wave-induced fluorescence
      spectroscopic (TREWIFS) techniques. Specifically, by varying the penetration
      depth of the evanescent field, variable-angle TREWIFS, coupled with variable
      angle evanescent wave-induced time-resolved fluorescence anisotropy measurements,
      allow us to monitor how fluorescence intensity and fluorescence depolarization
      vary normal to an interface as a function of time after excitation. We have
      applied this technique to the study of bovine serum albumin (BSA) complexed
      noncovalently with the fluorophore 1-anilinonaphthalene-8-sulfonic acid. The
      fluorescence decay varies as a function of the penetration depth of the
      evanescent wave in a manner that indicates a gradient of hydrophobicity through
      the adsorbed protein, normal to the interface. Restriction of the fluorescent
      probe's motion also occurs as a function of distance normal to the interface. The
      results are consistent with a model of partial protein denaturation: at the
      surface, an adsorbed BSA molecule unfolds, thus optimizing protein-silica
      interactions and the number of points of attachment to the surface. Further away,
      normal to the surface, the protein molecule maintains its coiled structure.

PMID- 14586519
TI  - Modulation of HERG channel inactivation by external cations.
AB  - We investigated the effect of external cations on the permeability
      characteristics and gating kinetics of the human ether- a- go- go-related gene
      (HERG) current using the whole-cell patch-clamp technique. Inward HERG currents
      were recorded on hyperpolarization in 140 mM external Cs(+) and Rb(+), as well as
      K(+). The permeability ratios of Rb(+) and Cs(+) relative to K(+) were 1.25 and
      0.56, respectively. Biphasic outward currents were recorded on depolarization in
      140 mM Cs(+) and in Rb(+ )with much smaller amplitude. The voltage dependence of
      inactivation was affected by external cations, such that the half-inactivation
      voltage shifted from -69.4+/-3.7 mV in K(+) to -30.7+/-1.6 mV in Cs(+) and to 
      35.8+/-1.9 mV in Rb(+) ( n=5). The time constants of inactivation were also
      changed significantly by external cations; tau of inactivation at +40 mV was
      16.4+/-2.2 ms in 140 mM K(+), 181+/-20.3 ms in Cs(+), and 94.1+/-7.6 ms in Rb(+)
      ( n=5). Voltage dependence of activation was not altered significantly. The
      inhibition of the rapid inactivation mechanism by large cations may suggest that
      the "foot-in-the-door" model of gating is involved in HERG channel inactivation.

PMID- 14586523
TI  - A large unilateral renal artery aneurysm in a young child.
AB  - The case of a 13-month-old boy with fibromuscular dysplasia (FMD) presenting with
      a large saccular aneurysm of the left renal artery and renovascular hypertension
      is reported. Renal and intrarenal arteries showed numerous small aneurysms
      alternating with stenoses. All arterial lesions were localized to the left
      kidney. After left nephrectomy, the patient's blood pressure normalized.
      Histopathologic examination of the arteries disclosed changes typical of medial
      fibroplasias, the most frequently described form of FMD in children. This
      diagnosis is rewarding as it represents a surgically curable cause of severe
      hypertension.

PMID- 14586520
TI  - Atomic force microscopy and scanning near-field optical microscopy studies on the
      characterization of human metaphase chromosomes.
AB  - A better knowledge of biochemical and structural properties of human chromosomes
      is important for cytogenetic investigations and diagnostics. Fluorescence in situ
      hybridization (FISH) is a commonly used technique for the visualization of
      chromosomal details. Localizing specific gene probes by FISH combined with
      conventional fluorescence microscopy has reached its limit. Also, microdissecting
      DNA from G-banded human metaphase chromosomes by either a glass tip or by laser
      capture needs further improvement. By both atomic force microscopy (AFM) and
      scanning near-field optical microscopy (SNOM), local information from G-bands and
      chromosomal probes can be obtained. The final resolution allows a more precise
      localization compared to standard techniques, and the extraction of very small
      amounts of chromosomal DNA by the scanning probe is possible. Besides new
      strategies towards a better G-band and fluorescent probe detection, this study is
      focused on the combination of biochemical and nanomanipulation techniques which
      enable both nanodissection and nanoextraction of chromosomal DNA.

PMID- 14586524
TI  - Tracheal web.
AB  - Congenital tracheal web is a rare entity often misdiagnosed as refractory asthma.
      Clinical suspicion based on patient history, examination, and pulmonary function
      tests should lead to its consideration. Bronchoscopy combined with CT imaging and
      multiplanar reconstruction is an accepted, highly sensitive means of diagnosis.

PMID- 14586526
TI  - Reply to Hoffer: the radiological spectrum of invasive aspergillosis in children:
      a 10-year review.

PMID- 14586525
TI  - Ultrasonographic assessment of the ectopic thyroid tissue in children with
      congenital hypothyroidism.
AB  - BACKGROUND: Ectopic thyroid tissue as a result of thyroid developmental
      abnormalities is the most frequent cause of congenital hypothyroidism (CH). It is
      diagnosed by using radionuclide thyroid scanning. OBJECTIVE. To evaluate the
      sensitivity of US in the detection of such ectopias and to describe their US
      pattern before and during treatment. MATERIALS AND METHODS: Forty-two neonates
      (group A; aged 11.3+/-4.0 days) and 33 older children (group B; aged 11.1+/-3.9
      years) with a biochemical diagnosis of CH and thyroid ectopia detected by
      radionuclide scanning were evaluated before (group A) and after (group B)
      treatment. Thyroid US included a survey of the pathway of the thyroglossal tract
      and an evaluation of the location, size, echogenicity and vascularity of any
      tissue along this pathway suggestive of thyroid ectopia. RESULTS: Thyroid ectopia
      was detected using US in 18 patients (24%) with a similar rate during the
      neonatal period and thereafter on therapy. Three patients demonstrated double
      ectopia. These 21 sites of ectopic thyroid tissue were located at the suprahyoid
      level (n=12), at the level of the hyoid (n=1), and at the infrahyoid level (n=8).
      The maximum diameter of the ectopic tissue ranged from 4 to 14 mm. In group A (9
      patients), the 11 ectopias were all hypervascular. These were hyperechoic in all
      but one neonate. In group B (9 patients), the ten ectopias were not vascular, and
      were hyper (n=3) or hypoechoic (n=7). CONCLUSIONS: US allows for detection of
      ectopic thyroid tissue, but with a lower detection rate than radionuclide
      scanning. However, it does provide a more detailed description of such ectopias.

PMID- 14586529
TI  - Perioperative penetration of metronidazole into muscle tissue: a microdialysis
      study.
AB  - OBJECTIVE: To evaluate the concentration of metronidazole in muscle tissue using
      microdialysis and to compare it with plasma concentration and in vitro-defined
      MIC(90) (minimal inhibiting concentration) for the most frequent anaerobic
      bacteria isolated in our hospital. MATERIALS AND METHODS: Six female patients
      scheduled for elective gynaecological surgery were included. Exclusion criteria
      were active inflammatory process and being overweight (BMI more than 30).
      Microdialysis catheters (CMA 60 catheters with 20 kDa cut-off membrane) were
      placed into the m. vastus lateralis. The microdialysis perfusion rate was 2
      microl/min. To assess in vivo recovery of the drug, retrodialysis with a 5-mg/l
      solution of metronidazole was performed. Microdialysis and blood samples were
      collected simultaneously 10 h after metronidazole administration. MIC(90) data
      were obtained from the database of the microbiology laboratory of the local
      hospital. RESULTS: Data from five patients were included in analysis. The
      metronidazole concentration in blood achieved a value of 16.5+/-4.6 mg/l at 30
      min (first available data), while in muscle a maximum level of 7.8+/-1.5 mg/l was
      achieved at 114 min. The mean MIC(90) for the Bacteroides fragilis group was
      0.25+/-0.26 mg/l. Data from mean plasma concentrations were fitted into the two
      compartmental model and time over MIC(90) and time over four times MIC(90) were
      calculated, which were 52.1+/-13.5 h and 33.2+/-8.7 h, respectively. The
      C(max)/MIC(90) ratio was 65.8+/-18.5 for plasma and 31.1+/-6.2 for muscle.
      CONCLUSION: The present data demonstrate that metronidazole penetrates well into
      muscle tissue. Muscle tissue concentrations reach values far greater than MIC(90)
      for the Bacteroides fragilis group and persist at such high levels for at least
      10 h.

PMID- 14586530
TI  - Incidence and severity of intravenous drug errors in a German hospital.
AB  - OBJECTIVE: To determine the incidence of errors in preparing and administering
      intravenous (i.v.) drugs, identify the stages in the process at which errors
      occurred and evaluate their clinical importance. METHODS: A prospective
      ethnographic study using disguised observation was carried out on two wards in
      one German non-university hospital. RESULTS: We observed 22 nurses administering
      122 i.v. drug preparations and administrations. One or more errors occurred in
      the preparation and administration of 58 of 122 i.v. drug doses (error rate 48%,
      95% confidence interval 39-57%). In total, 65 errors were identified. Of doses, 4
      had potentially severe errors (3%), 38 (31%) potentially moderate errors and 16
      (13%) potentially minor errors. Common errors included multiple step preparations
      and the co-administration of potentially incompatible drugs as intermittent
      infusions. CONCLUSION: A high incidence of i.v. drug errors was found in the
      study hospital. Effective strategies to reduce potentially harmful errors are
      urgently needed. Measures could include a reduction in the number of ward-based
      i.v. drug preparations, improvement of staff training and the introduction of
      ward-based clinical pharmacy services.

PMID- 14586528
TI  - Urinary excretion of total cystine and the dibasic amino acids arginine, lysine
      and ornithine in relation to genetic findings in patients with cystinuria treated
      with sulfhydryl compounds.
AB  - Advances in molecular genetics have brought a deeper understanding of cystinuria.
      This autosomal recessive disease, which is caused by a defective tubular
      reabsorption of cystine and the three dibasic amino acids arginine, lysine and
      ornithine, results in a lifelong risk of renal stone formation because of the low
      solubility of cystine in urine. Mutations detected within the two genes known to
      be associated with cystinuria, SLC3A1 (related to type I) and SLC7A9 (related to
      non-type I), cannot, however, in all cases explain the disease. Inasmuch as a
      high urinary concentration of cystine is the basis of stone formation in these
      patients, our aim was to measure urinary total cystine, arginine, lysine and
      ornithine, in patients currently lacking a full genetic explanation for their
      disease. Thirty-three patients with cystinuria who were on long-term treatment
      with tiopronin or D-penicillamine were divided into two groups. Group 1 comprised
      eight patients who carried mutation in one of the SLC3A1 alleles and two patients
      who completely lacked mutations both in the SLC3A1 and the SLC7A9 genes, that is
      genetic findings discordant with the increased urinary excretion of cystine and
      the dibasic amino acids in these patients. Group 2 comprised 23 patients
      homozygous for mutations within SLC3A1, that is genetic findings in accordance
      with the excretion pattern of classic type I cystinuria. When the two groups were
      compared, Group 1 had a significantly higher total urinary excretion of cystine (
      p<0.01) as well as of arginine, lysine and ornithine ( p<0.05) than Group 2.
      Also, when the two patients without mutations were excluded from the
      calculations, there still was a significant difference in the urinary excretion
      of total cystine ( p<0.05). This suggests that the two patients without any
      detected mutations in the two known cystine transport genes also contributed to
      the difference. These unexpected findings indicate that an additional gene or
      genes participate in the urinary cystine reabsorption in the cystinuric patients
      who currently are without a full genetic explanation for their disease.

PMID- 14586531
TI  - The integration of multiple proprioceptive information: effect of ankle tendon
      vibration on postural responses to platform tilt.
AB  - Previous studies have looked at co-processing of multiple proprioceptive inputs
      but few have investigated the effect of separate dynamic and tonic predominantly
      proprioceptive disruptions applied concurrently at the same segment. The purpose
      of the present study was to investigate how simultaneous ankle tendon vibration,
      a tonic stimulus, with a dynamic toes-up (TU) or toes-down (TD) platform
      perturbation (1) affects postural stability and (2) influences the adaptation
      process. Sixteen normal subjects (ten male, six female, mean age 26 +/- 4.8
      years) stood blindfolded on a moving platform with vibrators attached bilaterally
      over the Achilles tendons. Participants were tested in quiet stance (QS), and
      with five successive TU and TD tilts. All tests were conducted both with (QS+V,
      TU+V, TD+V) and without vibration. Centre of pressure (CoP) displacements and
      pitch angular trunk velocity were recorded. Results for QS+V showed a significant
      1.02-cm backward CoP displacement (P<0.01) and a significant increase in trunk
      velocity (peak-to-peak amplitude, P<0.05; SD of trunk velocity, P<0.05). TU+V
      resulted in a non-significant increase of maximum backwards CoP displacement when
      compared to TU alone. In addition, no notable effect of vibration on other
      measures of CoP (pre-tilt position, SD and area of sway) and trunk velocity (peak
      to-peak, SD and area of sway) indicates that TU+V does not introduce
      significantly greater instability compared to tilt alone. In the TD condition,
      vibration was found to be a stabilising influence, causing a significant shift of
      the mean pre-tilt position 0.85 cm backwards (P<0.01) and a substantial decrease
      in the area of forward CoP displacement (P<0.01). However, maximum forwards CoP
      displacement and trunk velocity measures were not significantly altered during
      TD+V. Furthermore, in neither TU nor TD was the time-course or pattern of
      adaptation disrupted by the additional application of vibration. In conclusion,
      although vibration significantly affects postural measures when applied in
      isolation, this finding does not hold when it is applied in combination with a
      more dynamic stimulus. Instead it seems that once postural stability has been
      disrupted the central nervous system can rapidly assess information from a weaker
      tonic input and utilise or suppress it appropriately, depending on its effect
      towards overall postural control. It can be concluded that postural responses to
      the concurrent application of different predominantly proprioceptive stimuli are
      dependent upon the type of stimulus and the ability of the central nervous system
      to rapidly assess and re-weigh available sensory inputs.

PMID- 14586534
TI  - Writing an eye-catching, high-impact paper.

PMID- 14586535
TI  - Simple and rapid catalytic spectrophotometric determination of superoxide anion
      radical and superoxide dismutase activity in natural medical vegetables using
      phenol as the substrate for horseradish peroxidase.
AB  - The coupling reaction of 4-aminoantipyrine (4-AAP) with phenol using the
      superoxide anion radical (O2-*) as oxidizing agent under the catalysis of
      horseradish peroxidase (HRP) was studied. Based on the reaction, O2-* produced by
      irradiating vitamin B2 (VB2) was spectrophotometrically determined at 510 nm.
      Under the optimum experimental conditions, the relationship between A510 and O2-*
      concentration was linear in the range 9.14x10(-6)-1.2x10(-4) mol L(-1). The
      detection limit was determined to be 1.37x10(-6) mol L(-1). A possible reaction
      mechanism was discussed. The effect of interferences and surfactants on the
      determination of O2-* was also investigated. The proposed method was applied to
      determine superoxide dismutase activity in garlic, scallion, and onion with
      satisfactory results.

PMID- 14586536
TI  - Colon cancer risk factors from nutrition.
AB  - Nutrition and health are closely connected and malnutrition can seriously
      endanger health. The consequences are higher risks of developing diseases. Of
      these, cancers are of special importance. The most frequent nutrition-associated
      type of cancer is colon cancer. This review summarises the predisposing factors
      for the development of colon cancer, and molecular mechanisms responsible for
      sporadic colon cancer. Moreover, it is pointed out that individual genetic
      predisposition such as polymorphisms of biotransformation systems might affect
      susceptibility to cancer risk factors. Selected findings of epidemiological
      research and nutritional habits, foods, and metabolites that could increase
      cancer risk are discussed. Furthermore, toxicological assessment of food-related
      risk factors, e.g. heterocyclic amines, and potential protective effects of food
      ingredients, e.g. the induction of phase II enzymes or removal of already
      degenerated cells from tissue by apoptosis, inhibition of proliferation, and cell
      differentiation are discussed. Risks are not necessarily reduced by avoiding
      certain substances but by healthy and well-balanced nutrition. Knowledge of
      individual susceptibility will also make it possible to recognise risks and
      design more specific nutritional recommendations.

PMID- 14586537
TI  - Time-resolved sensor arrays.

PMID- 14586532
TI  - Initiating extension of the lower limbs in subjects with complete spinal cord
      injury by epidural lumbar cord stimulation.
AB  - We provide evidence that the human spinal cord is able to respond to external
      afferent input and to generate a sustained extension of the lower extremities
      when isolated from brain control. The present study demonstrates that sustained,
      nonpatterned electrical stimulation of the lumbosacral cord--applied at a
      frequency in the range of 5-15 Hz and a strength above the thresholds for
      twitches in the thigh and leg muscles--can initiate and retain lower-limb
      extension in paraplegic subjects with a long history of complete spinal cord
      injury. We hypothesize that the induced extension is due to tonic input applied
      by the epidural stimulation to primary sensory afferents. The induced volleys
      elicit muscle twitches (posterior root muscle-reflex responses) at short and
      constant latency times and coactivate the configuration of the lumbosacral
      interneuronal network, presumably via collaterals of the primary sensory neurons
      and their connectivity with this network. We speculate that the volleys induced
      externally to the lumbosacral network at a frequency of 5-15 Hz initiate and
      retain an "extension pattern generator" organization. Once established, this
      organization would recruit a larger population of motor units in the hip and
      ankle extensor muscles as compared to the flexors, resulting in an extension
      movement of the lower limbs. In the electromyograms of the lower-limb muscle
      groups, such activity is reflected as a characteristic spatiotemporal pattern of
      compound motor-unit potentials.

PMID- 14586538
TI  - Anandamide inhibits the DOI-induced head-twitch response in mice.
AB  - RATIONALE: Recently, Delta(9)-tetrahydrocannabinol (THC), the major psychoactive
      component of marijuana, and synthetic cannabinoid receptor agonists reportedly
      reduced the head-twitches induced by the 5-HT(2A/2C) receptor agonist 1-(2,5
      dimethoxy 4-iodophenyl)-2-amino propane (DOI) in mice, which is mediated via the
      activation of 5-HT(2A) receptor. However, the effect of endogenous cannabinoid
      anandamide on the head-twitch response has not been studied. OBJECTIVES: In this
      study, we investigated the effect of anandamide on the DOI-induced head-twitch
      response in mice. METHODS: Five minutes after the injection of DOI (5 mg/kg IP),
      the number of head-twitches was counted for a 5-min period. THC or anandamide was
      injected IP 60 min or 10 min before the number of head-twitches was counted,
      respectively. RESULTS: THC and anandamide each reduced the DOI-induced head
      twitch response. The inhibition of the DOI-induced head-twitch response by THC
      was reversed by SR141716A (N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)
      4-methyl-3-pyrazole-carboxamide), a CB(1) receptor antagonist, while the effect
      of anandamide was not blocked by SR141716A. Cyclooxygenase (COX) inhibitors such
      as aspirin and indomethacin reversed the inhibition of the DOI-induced head
      twitch response by anandamide. On the other hand, COX inhibitors did not affect
      the inhibition of the DOI-induced head-twitch response by THC. CONCLUSIONS: Taken
      together, these findings suggest that the endocannabinoid anandamide may inhibit
      5-HT(2A) receptor-mediated function via the arachidonic acid cascade, but not via
      a direct interaction with the CB(1) cannabinoid receptor, and that the mechanism
      of its action is clearly different from that of THC.

PMID- 14586539
TI  - Topiramate attenuates exaggerated acoustic startle in an animal model of PTSD.
AB  - RATIONALE: Exaggerated acoustic startle is a prominent symptom of post-traumatic
      stress disorder (PTSD); however, its physiological basis is not well understood,
      and there are few available treatments. Neurobiological research has suggested
      that anti-kindling agents and/or glutamate antagonists can attenuate the acoustic
      startle response (ASR) in animal models. The anticonvulsant topiramate is an AMPA
      antagonist that also demonstrates potent anti-kindling effects and may,
      therefore, have promise in treating trauma-enhanced ASR. OBJECTIVE: To evaluate
      the ability of topiramate to attenuate stress-induced increases in ASR in a
      previously validated animal model of PTSD. METHODS: Male Sprague-Dawley rats (
      n=36) served as controls or received single prolonged stress (SPS). SPS consisted
      of 2 h restraint, forced swim and ether anesthesia, then a 7-day "undisturbed"
      period. Animals then received vehicle, 10 mg/kg or 30 mg/kg of topiramate orally,
      twice daily for 7 days. ASR was assessed for all animals before and after the
      study, in light and dark environments. RESULTS: SPS produced a sustained increase
      in the ASR in both environments, an effect that was significantly reduced by
      topiramate. Meanwhile the ASR of control animals remained unaffected by
      topiramate. CONCLUSIONS: The current results provide one of the few
      demonstrations of a single stress episode producing sustained enhancement of ASR.
      In addition, topiramate demonstrates promise in treating exaggerated acoustic
      startle symptoms in PTSD or other stress-related disorders.

PMID- 14586540
TI  - The plant-derived hallucinogen, salvinorin A, produces kappa-opioid agonist-like
      discriminative effects in rhesus monkeys.
AB  - RATIONALE: Salvinorin A is the active component of the hallucinogenic plant
      Salvia divinorum. The potential mode of action of this hallucinogen was unknown
      until recently. A recent in vitro study detected high affinity and efficacy of
      salvinorin A at kappa-opioid receptors. It was postulated that salvinorin A would
      produce discriminative stimulus effects similar to those of a high efficacy kappa
      agonist (U69,593) in rhesus monkeys. METHODS: Monkeys were previously trained to
      discriminate U69,593 (0.0056 or 0.013 mg/kg; s.c.) from vehicle in a food
      reinforced FR20 (fixed ratio 20) operant conditioning procedure (n=3). The
      ability of salvinorin A to cause generalization (> or =90% U69,593-appropriate
      responding) was examined in time course and cumulative dose-effect curve studies.
      RESULTS: All subjects dose-dependently emitted full U69,593-appropriate
      responding after salvinorin A (0.001-0.032 mg/kg, SC). Salvinorin A-induced
      generalization started 5-15 min after injection, and dissipated by 120 min. The
      opioid antagonist quadazocine (0.32 mg/kg) fully blocked the effects of
      salvinorin A. The kappa-selective antagonist GNTI (1 mg/kg; 24 h pretreatment)
      did not cause significant antagonism of the effects of salvinorin A (GNTI, under
      these conditions, was only effective as an antagonist in two of three monkeys).
      The NMDA antagonist ketamine (0.1-3.2 mg/kg) was not generalized by any subject,
      indicating that not all compounds that produce hallucinogenic or psychotomimetic
      effects in humans are generalized by subjects trained to discriminate U69,593.
      CONCLUSIONS: The naturally occurring hallucinogen salvinorin A produces
      discriminative stimulus effects similar to those of a high efficacy kappa-agonist
      in non-human primates.

PMID- 14586541
TI  - Brain tyrosine depletion attenuates haloperidol-induced striatal dopamine release
      in vivo and augments haloperidol-induced catalepsy in the rat.
AB  - RATIONALE: There are conflicting reports as to whether alterations in tyrosine
      levels affect functional indices of striatal dopamine (DA) transmission. Since
      the DA antagonist haloperidol (HAL) increases striatal DA release and induces
      catalepsy through its actions on striatal DA systems, it provides a useful
      paradigm to assess both neurochemical and behavioral effects of lowering brain
      tyrosine levels. OBJECTIVES: To determine how brain tyrosine depletion affects
      HAL-induced catalepsy and striatal DA release in awake, freely moving rats.
      METHODS: In male rats, a control or tyrosine- and phenylalanine-free neutral
      amino acid solution NAA(-) (IP) was administered 30-60 min prior to HAL (IP). In
      one cohort, striatal microdialysate was assayed for DA levels. In a parallel
      cohort, catalepsy was measured using the bar test. RESULTS: NAA (-) reduced
      striatal tyrosine levels by 60%. The latter did not affect basal striatal DA
      release, but consistently delayed the attainment of maximal HAL-induced (0.19
      mg/kg and 0.25 mg/kg SC) striatal DA release; the latter was abolished by
      administration of tyrosine. NAA(-) also potentiated HAL-induced catalepsy.
      CONCLUSIONS: Acute brain tyrosine depletion attenuates HAL-induced striatal DA
      release and potentiates haloperidol-induced catalepsy. Both effects can be
      reversed by administration of tyrosine. Overall, the data indicate that tyrosine
      depletion affects both neurochemical and behavioral indices of striatal DA
      release.

PMID- 14586542
TI  - Inhibition of fear potentiated startle in rats following peripheral
      administration of secretin.
AB  - RATIONALE: Previous results indicate that peripheral administration of secretin
      leads to robust Fos protein expression in the central nucleus of the rat
      amygdala. The implications of this observation on rat brain function, if any,
      remain unclear. OBJECTIVES: We examined the effect of systemic secretin
      administration on the expression of fear-potentiated startle in rats, a
      behavioral response known to require an intact, functional central nucleus of the
      amygdala. METHODS: Rats were trained to associate a neutral light conditioned
      stimulus (CS) with footshock, a fear-inducing unconditioned stimulus (US). Twenty
      four hours later, rats were administered secretin or vehicle and were tested
      immediately for their startle response to a loud noise in the presence or absence
      of the light. RESULTS: Within a dose range relevant to its clinical use in
      autistic children, secretin dose-dependently decreased the magnitude of fear
      potentiated startle in rats. CONCLUSIONS: This investigation provides additional
      evidence that systemically administered secretin can influence a neural network
      implicated in the acquisition and expression of emotional behaviors, including
      fear and anxiety.

PMID- 14586543
TI  - Hepatotoxicity of 3,4-methylenedioxyamphetamine and alpha-methyldopamine in
      isolated rat hepatocytes: formation of glutathione conjugates.
AB  - The amphetamine designer drugs 3,4-methylenedioxymethamphetamine (MDMA or
      "ecstasy") and its N-demethylated analogue 3,4-methylenedioxyamphetamine (MDA or
      "love") have been extensively used as recreational drugs of abuse. MDA itself is
      a main MDMA metabolite. MDMA abuse in humans has been associated with numerous
      reports of hepatocellular damage. Although MDMA undergoes extensive hepatic
      metabolism, the role of metabolites in MDMA-induced hepatotoxicity remains
      unclear. Thus, the aim of the present study was to evaluate the effects of MDA
      and alpha-methyldopamine (alpha-MeDA), a major metabolite of MDA, in freshly
      isolated rat hepatocyte suspensions. The cells were incubated with MDA or alpha
      MeDA at final concentrations of 0.1, 0.2, 0.4, 0.8, or 1.6 mM for 3 h. The toxic
      effects induced following incubation of hepatocyte suspensions with these
      metabolites were evaluated by measuring cell viability, the extent of lipid
      peroxidation, levels of glutathione (GSH) and glutathione disulfide (GSSG), the
      formation of GSH conjugates, and the activities of GSSG reductase (GR), GSH
      peroxidase (GPX), and GSH S-transferase (GST). MDA induced a concentration- and
      time-dependent GSH depletion, but had a negligible effect on lipid peroxidation,
      cell viability, or on the activities of GR, GPX, and GST. In contrast, alpha-MeDA
      (1.6 mM, 3 h) induced a marked depletion of GSH accompanied by a loss on cell
      viability, and decreases in GR, GPX and GST activities, although no significant
      effect on lipid peroxidation was found. For both metabolites, GSH depletion was
      not accompanied by increases in GSSG levels; rather, 2-(glutathion- S-yl)-alpha
      MeDA and 5-(glutathion- S-yl)-alpha-MeDA were identified by HPLC-DAD/EC within
      cells incubated with MDA or alpha-MeDA. The results provide evidence that one of
      the early consequences of MDMA metabolism is a disruption of thiol homeostasis,
      which may result in loss of protein function and the initiation of a cascade of
      events leading to cellular damage.

PMID- 14586544
TI  - Biochemical and genetic characterization of ChiA, the major enzyme component for
      the solubilization of chitin by Cellulomonas uda.
AB  - Cellulomonas uda efficiently solubilized chitinous substrates with a simple
      chitinase system composed of an endochitinase, designated ChiA, which hydrolyzed
      insoluble substrates into long-chain chitooligosaccharides, and an as yet
      uncharacterized exochitinase activity. ChiA, isolated from culture supernatant
      fluids, was found to be a glycosylated endochitinase with an apparent molecular
      mass of approximately 70 kDa and pI of 8.5. The gene encoding ChiA was cloned in
      Escherichia coli and sequenced, revealing an open reading frame of 1,716 bp
      encoding a 571-amino-acid protein with a predicted molecular mass of 59.2 kDa.
      The region upstream of chiA included a conserved -35 hexamer flanked by two
      direct repeats analogous to those found in many Streptomyces chitinase promoters,
      and thought to function as binding sequences for regulatory proteins. Analysis of
      the deduced amino acid sequence showed a modular protein consisting of a signal
      peptide at its N terminus, a family 2 carbohydrate-binding module (CBM2) that was
      closely related to the substrate-binding domains of glycosyl hydrolases from
      distantly related bacteria, and a family 18 glycosyl hydrolase catalytic module
      related to Streptomyces chitinases. In contrast to the fibronectin type III
      domains of Streptomyces chitinases, the linker region between modules in ChiA
      consisted of a long proline- and threonine-rich module, thought to contribute to
      the glycosylation and flexibility of the mature protein.

PMID- 14586545
TI  - Acoustic response properties of lagenar nerve fibers in the sleeper goby,
      Dormitator latifrons.
AB  - Auditory and vestibular functions of otolithic organs vary among vertebrate taxa.
      The saccule has been considered a major hearing organ in many fishes. However,
      little is known about the auditory role of the lagena in fishes. In this study we
      analyzed directional and frequency responses from single lagenar fibers of
      Dormitator latifrons to linear accelerations that simulate underwater acoustic
      particle motion. Characteristic frequencies of the lagenar fibers fell into two
      groups: </=50 Hz and 80-125 Hz. We observed various temporal response patterns:
      strong phase-locking, double phase-locking, phase-locked bursting, and non-phase
      locked bursting. Some bursting responses have not been previously observed in
      vertebrate otolithic nerve fibers. Lagenar fibers could respond to accelerations
      as small as 1.1 mm s(-2). Like saccular fibers, lagenar fibers were directionally
      responsive and decreased directional selectivity with stimulus level. Best
      response axes of the lagenar fibers clustered around the lagenar longitudinal
      axis in the horizontal plane, but distributed in a diversity of axes in the mid
      sagittal plane, which generally reflect morphological polarizations of hair cells
      in the lagena. We conclude that the lagena of D. latifrons plays a role in sound
      localization in elevation, particularly at high stimulus intensities where
      responses of most saccular fibers are saturated.

PMID- 14586546
TI  - G. Frank Lydston (1858-1923) revisited: androgen therapy by testicular
      implantation in the early twentieth century.
AB  - At the beginning of the twentieth century the transplantation or implantation of
      either human or animal testicular tissue was an appealing form of androgen
      therapy in hypogonadal and aging males. This article on the history of medicine
      discusses the work of the American urologist G. Frank Lydston from Chicago, who
      was a well-known and respected surgeon in the academic world and was involved in
      the early clinical trials of this procedure.

PMID- 14586547
TI  - Androgen and estrogen receptors in the human corpus cavernosum penis:
      immunohistochemical and cell culture results.
AB  - Despite the central and peripheral effects of androgens on the nervous system,
      the local effects of androgens in the corpus cavernosum penis and their
      importance for erectile function is still unclear. In this study corpus
      cavernosum biopsies of eight adult potent patients, aged 19-63 years, undergoing
      penile deviation surgery (group A) and 12 patients undergoing male-to-female
      transsexual surgery (group B) were immunostained for nuclear androgen and
      estrogen-alpha receptors. Additionally, primary corpus cavernosum endothelial
      cell cultures were obtained from six transsexual patients and exposed to
      testosterone, dihydrotestosterone, estradiol and progesterone likewise for 7
      days. Total cell count was performed and cell metabolic activity was measured by
      a tetrazolium salt-based assay. Androgen and estrogen-alpha receptors were
      detected in stromal as well as in endothelial cells. Of all cell nuclei, 74.9%
      (SD 16.4) in group A and 63.5% (SD 17.1) in group B were positively stained for
      androgen receptors. The respective percentage of estrogen receptors was 11% (SD
      9.5) and 21.2% (SD 12.6). An age-dependent difference in receptor distribution
      was not observed in either group. In the cell culture system only cultures
      exposed to testosterone and dihydrotestosterone showed a dose-dependent increase
      of cell metabolic activity compared to the cultures supplemented with estradiol
      and progesterone. The significant and age-independent high androgen and low
      estrogen-alpha receptor distribution found in both groups suggests a possible
      peripheral effect of androgens at the level of the corpus cavernosum penis in
      adult humans. This is supported by the observed effect of testosterone and
      dihydrotestosterone on cell count and endothelial cell metabolism in our cell
      culture system. The role of estrogens remains unclear.

PMID- 14586549
TI  - Spontaneous rupture of mesenteric dermoid cyst: a rare cause of abdominal pain.

PMID- 14586550
TI  - Somatic embryogenesis and plant regeneration from immature zygotic embryos of
      Cryptomeria japonica D. Don.
AB  - This report describes the successful plant regeneration via somatic embryogenesis
      from immature zygotic embryos of Cryptomeria japonica D. Don. For the induction
      of embryogenic tissue, we determined that the optimal medium contained N6
      benzyladenine and 2,4-dichlorophenoxyacetic acid. Immature zygotic embryos that
      were collected at the end of June yielded embryogenic tissue at the highest
      frequency. Embryogenic tissues that had proliferated in liquid medium included
      small and loosely packed cells and elongating or elongated cells. We used ten
      cell lines to determine the optimal medium for the development of somatic
      embryos. Induced somatic embryos germinated with synchronous sprouting of
      cotyledons, hypocotyls and roots. Gibberellin A3 in the germination medium had a
      positive effect on both the elongation of hypocotyls and the survival of
      seedlings. The frequencies of induction and germination of somatic embryos
      differed among the cell lines examined. Most of the seedlings grew normally. This
      system of somatic embryogenesis required 4-5 months for the regeneration of C.
      japonica plantlets from immature zygotic embryos.

PMID- 14586551
TI  - A novel selection system for potato transformation using a mutated AHAS gene.
AB  - Acetohydroxyacid synthase (AHAS) is the target enzyme for a number of herbicides.
      A S653N mutation in the AHAS gene results in an increased tolerance to
      imidazolinone herbicides. We have investigated the use of the mutated gene as
      selection gene for potato transformation. This resulted in a transformation
      system with a very high transformation frequency and low rate of escapes. The
      mutated AHAS gene was introduced into transformed potato together with a beta
      glucuronidase (GUS) gene. Selection on 0.5 microM Imazamox yielded GUS expression
      in 93-100% of regenerated shoots. Furthermore the mutated AHAS gene was used as
      selection gene for production of high-amylopectin potato lines. The high
      transformation frequency was verified and potato lines with the desirable starch
      quality were obtained.

PMID- 14586548
TI  - Androgens and prostate cancer.
AB  - Over 60 years ago Huggins and Hodges demonstrated the importance of androgens and
      prostate cancer. Since then, significant research has revealed that this
      relationship is multi-faceted and is interwoven with different signaling cascades
      and protein coactivators. The complex interrelationship between hormone and
      cancer is best exemplified by the recurrence and progression of prostate cancer
      after hormonal therapy to a lethally resistant phenotype despite initially
      encouraging therapeutic responses. If we are to significantly improve survival
      with novel therapies, further understanding of the emergence of this resistant
      phenotype is essential. The purpose of this article is to review the mechanisms
      of androgen action and its relation to hormonal therapy and mechanisms of
      hormonal resistance.

PMID- 14586552
TI  - Development of a novel Agrobacterium-mediated transformation method to recover
      transgenic Brassica napus plants.
AB  - We report here an in planta method to produce transgenic Brassica napus plants.
      The procedure included Agrobacterium-mediated inoculation of plants at various
      development stages along with a vacuum infiltration step. The flowering stage
      appeared to be the most receptive stage for transformation and production of
      transgenic plants. In some cases, the flowering stage was induced either by cold
      treatment or by high density planting. Molecular and genetic analysis revealed
      that single and multiple copy events were generated and that the transgenes were
      transmitted to the T1 and T2 progeny in a Mendelian fashion.

PMID- 14586553
TI  - Serum homocysteine level is higher in Behcet's disease with vascular involvement.
AB  - OBJECTIVE: Behcet's disease (BD) is a multisystemic inflammatory disorder of
      unknown etiology that is sometimes associated with thrombosis. However, the
      mechanism of hypercoagulability is not known. In this study, we investigated
      whether hyperhomocysteinemia, being a well-known risk factor for thrombosis, is
      also a contributing risk factor to venous and arterial thromboses of BD. METHODS:
      Forty-five patients with BD and 40 healthy subjects were included in the study.
      Sixteen patients had vascular involvement. Serum homocysteine levels were
      determined by fluorescence polarization immunoassay. RESULTS: In male patients,
      the frequency of vascular involvement was significantly higher than in females
      (46.7% vs 13.3%, P < 0.05). Serum homocysteine levels were significantly higher
      in patients with BD than healthy controls (P < 0.01), in patients with vascular
      involvement than those with mucocutaneous involvement (P < 0.01) and healthy
      controls (P = 0.001), and in male patients than in female patients (P < 0.001).
      There was no significant difference in homocysteine levels between the BD
      patients with mucocutaneous involvement and healthy subjects. In multiple
      regression analysis, serum homocysteine level was independently associated with
      thrombosis (odds ratio 1.29, P < 0.01), but male sex was not. CONCLUSIONS: This
      preliminary study suggests that elevated serum homocysteine levels may play some
      role in the development of venous and arterial thromboses in BD.

PMID- 14586554
TI  - Gene disruption in Trichoderma atroviride via Agrobacterium-mediated
      transformation.
AB  - A modified Agrobacterium-mediated transformation method for the efficient
      disruption of two genes encoding signaling compounds of the mycoparasite
      Trichoderma atroviride is described, using the hph gene of Escherichia coli as
      selection marker. The transformation vectors contained about 1 kb of 5' and 3'
      non-coding regions from the tmk1 (encoding a MAP kinase) or tga3 (encoding an
      alpha-subunit of a heterotrimeric G protein) target loci flanking a selection
      marker. Transformation of fungal conidia and selection on hygromycin-containing
      media applying an overlay-based procedure, which overcomes the lack of formation
      of distinct single colonies by the fungus, led to stable clones for both
      disruption constructs. Southern and PCR analyses proved gene disruption by single
      copy homologous integration with a frequency of approximately 60% for both genes;
      and the loss of tmk1 and tga3 transcript formation in the disruptants was
      demonstrated by RT-PCR.

PMID- 14586556
TI  - An improved and highly standardised transformation procedure allows efficient
      production of single and multiple targeted gene-knockouts in a moss,
      Physcomitrella patens.
AB  - The moss Physcomitrella patens is the only land plant known to date with highly
      efficient homologous recombination in its nuclear DNA, making it a unique model
      for plant functional genomics approaches. For high-throughput production of
      knockout plants, a robust transformation system based on polyethylene glycol
      mediated transfection of protoplasts was developed and optimised. Both the DNA
      conformation and pre-culture of plants used for protoplast isolation
      significantly affected transformation efficiencies. Employing a newly developed
      PCR high-throughput method, the gene-targeting efficiency in more than 1000
      plants transformed with different cDNA-based knockout constructs was determined
      and analysed with regard to the length and intron/exon structure of the
      homologous gene locus. Different targeting constructs, each containing an
      identical selectable marker gene, were applied as batch DNA in a single
      transformation experiment and resulted in double-knockout plants. Thus, the fast
      and efficient generation of multiple targeted gene-knockouts is now feasible in
      Physcomitrella.

PMID- 14586555
TI  - Mosaic (MSC) cucumbers regenerated from independent cell cultures possess
      different mitochondrial rearrangements.
AB  - Passage of the highly inbred cucumber ( Cucumis sativus L.) line B through cell
      culture produces progenies with paternally transmitted, mosaic (MSC) phenotypes.
      Because the mitochondrial genome of cucumber shows paternal transmission, we
      evaluated for structural polymorphisms by hybridizing cosmids spanning the entire
      mitochondrial genome of Arabidopsis thaliana L. to DNA-gel blots of four
      independently generated MSC and four wild-type cucumbers. Polymorphisms were
      identified by cosmids carrying rrn18, nad5-exon2, rpl5, and the previously
      described JLV5 deletion. Polymorphisms revealed by rrn18 and nad5-exon2 were due
      to one rearrangement bringing together these two coding regions. The polymorphism
      revealed by rpl5 was unique to MSC16 and was due to rearrangement(s) placing the
      rpl5 region next to the forward junction of the JLV5 deletion. The rearrangement
      near rpl5 existed as a sublimon in wild-type inbred B, but was not detected in
      the cultivar Calypso. Although RNA-gel blots revealed reduced transcription of
      rpl5 in MSC16 relative to wild-type cucumber, Western analyses revealed no
      differences for the RPL5 protein and the genetic basis of the MSC16 phenotype
      remains enigmatic. We evaluated 17 MSC and wild-type lines regenerated from
      independent cell-culture experiments for these structural polymorphisms and
      identified eight different patterns, indicating that the passage of cucumber
      through cell culture may be a unique mechanism to induce or select for novel
      rearrangements affecting mitochondrial gene expression.

PMID- 14586558
TI  - Fetal bovine serum, but not human serum, inhibits the in vitro cytotoxicity of ET
      743 (Yondelis, trabectedin), an example of potential problems for extrapolation
      of active drug concentrations from in vitro studies.

PMID- 14586557
TI  - A phase II study of intravenous exatecan mesylate (DX-8951f) administered daily
      for 5 days every 3 weeks to patients with advanced ovarian, tubal or peritoneal
      cancer resistant to platinum, taxane and topotecan.
AB  - BACKGROUND: DX-8951f is a water-soluble camptothecin derivative with greater in
      vivo and in vitro activity than topotecan or irinotecan. The objectives of this
      phase II study were to determine the antitumor activity, safety and
      pharmacokinetic profile of DX-8951f administered intravenously for five
      consecutive days, every 3 weeks in patients with advanced ovarian, tubal and
      peritoneal cancer resistant to platinum, taxane and topotecan. METHODS: Enrolled
      in the study at The University of Texas M. D. Anderson Cancer Center were 16
      patients with measurable cancer resistant to platinum, taxane and topotecan. All
      16 patients were assessable for safety and 15 for efficacy analyses. Treatment
      consisted of a daily infusion of DX-8951f at 0.3 mg/m(2) per day (except for one
      minimally pretreated patient who started at 0.5 mg/m(2) per day) over 30 min for
      five consecutive days every 3 weeks. The pharmacokinetic and excretory profiles
      of DX-8951, the anhydrous form of DX-8951f, were also characterized. RESULTS:
      Disease was stable in 7 of 16 patients (44%) (4 minor response and 3 stable
      disease). The median time to tumor progression was 43 days (95% CI 37-92 days).
      The median overall survival was 117 days (95% CI 90-279 days). The main toxic
      effect was neutropenia and leukopenia with 50% of patients experiencing grade 3
      or 4 neutropenia and leukopenia. One episode of neutropenic fever was observed.
      Grade 3 or more anemia and thrombocytopenia were seen in 25% and 13% of patients,
      respectively. Grade 3 nonhematologic side effects included nausea (25% of
      patients) and fatigue (19%). Other side effects were not more than grade 2, and
      included gastrointestinal dysfunction, stomatitis, dermatitis, alopecia, liver
      dysfunction and drug fever. DX-8951 displayed linear pharmacokinetic
      characteristics at the doses administered. The average plasma clearance, total
      volume of distribution, and terminal elimination half-life were 2.1 l/h per m(2),
      20 l/m(2) and 9.5 h, respectively. CONCLUSIONS: DX-8951f administered
      parenterally as a single agent daily at a dose of either 0.5 or 0.3 mg/m(2) per
      day for 5 days is feasible in patients with advanced ovarian, tubal and
      peritoneal cancer resistant to platinum, taxane and topotecan. Although no
      responses were observed, a significant number of patients had stable disease with
      a decrease in CA-125 levels. In this heavily pretreated population, DX-8951f has
      clinically relevant hematologic and gastrointestinal toxicities in about 25% of
      patients. DX-8951 appeared to have linear pharmacokinetic characteristics on the
      basis of multiple administrations.

PMID- 14586559
TI  - TNF-alpha induces changes in LDH isotype profile following triggering of
      apoptosis in PBL of non-Hodgkin's lymphomas.
AB  - Based on the possibility of tumor necrosis factor (TNF)-alpha to perform multiple
      and opposite biologic effects, we simultaneously investigated in vitro its
      effects on intracellular lactate dehydrogenase (LDH)-H and LDH-M isoenzyme
      activity and morphological characteristics following induction of apoptosis in
      peripheral blood mononuclear cells (PBMC) of non-Hodgkin's lymphoma patients
      (NHL) prior to and after the end of applied chemotherapy. TNF-alpha showed a
      significant increase ( p<0.05) of LDH-H and LDH-M activity in sonified PBMC of
      healthy controls after 18 h cultures accompanied with an increase of apoptotic
      index (AI) from 2.3 to 16.2%. Contrary to this, in PBMC of NHL patients prior to
      therapy TNF-alpha induced a significant decrease ( p<0.05) of LDH-H isotype
      activity. In patients after administration of chemotherapy, TNF-alpha in a dose
      of 100 U/ml induced a significant increase ( p<0.05) of LDH-M isotype activity,
      but not of LDH-H. In the PBMC of NHL patients prior to chemotherapy, TNF-alpha in
      vitro induced an increase of AI from 2.8 up to 6.8%, while in PBMC of NHL
      patients after applied chemotherapy AI changed from 7.2 to 14.4%. However, there
      was no significant difference in the increase of apoptosis in PBMC of NHL
      patients with high-grade malignancy and high rate response among patients who
      received first-line therapy, high-dose therapy, or third-line therapy regimens
      after in vitro TNF-alpha treatment. These results indicated different
      susceptibilities of PBMC of NHL to TNF-alpha when effects were analyzed by
      determination of intracellular LDH isotype profile and induction of apoptosis
      prior to and after administration of therapy in comparison to effects on healthy
      controls PBMC.

PMID- 14586561
TI  - Korner's septum (petrosquamosal lamina) and chronic ear disease.
AB  - To assess the clinical significance of Korner's septum (KS) or petrosquamosal
      (PS) lamina in different chronic ear pathologies, a surgical and anatomic study
      was carried out, in which the significance of KS was assessed in various otologic
      diseases. Of 639 patients who underwent ear surgery between 1998 and 2001, 426
      were included in the study. The diagnoses were chronic otitis media without
      cholesteatoma (COM), tympanosclerosis (TS), adhesive otitis media (AOM) and
      cholesteatoma (COL) in 160, 100, 70 and 96 patients respectively. The operative
      records of the patients were reviewed for the presence of KS. There was antral
      blockage by KS in all patients who also had Cog (the middle portion of the PS
      lamina). KS was mostly seen in cases of TS. The prevalence of KS was not
      significantly different when the result of the COM group was compared with that
      of the COL and AOM groups ( p>0.05). The prevalence of KS was significantly
      higher in patients with TS than in those with COM. Both antral and epitympanic
      blockages were more prevalent in cases of TS than in those of COM (chi(2) =3.9, p
      =0.04 and chi(2) =6.6, p =0.01 respectively). There is a significant association
      between the presence of KS and TS. Based on this finding, it is recommended that
      a mastoidectomy be performed in cases of severe tympanosclerosis in order to
      remove KS. How the removal of this anatomic impact will affect the natural course
      of the disease is still a question that needs further investigation.

PMID- 14586562
TI  - Topographic anatomy of the lingual nerve and variations in communication pattern
      of the mandibular nerve branches.
AB  - We made a thorough observation of the morphology and course of the lingual nerve
      (LN) and inferior alveolar nerve (IAN) to clarify their topographical
      relationships in the infratemporal fossa and in the paralingual area. Thirty-two
      Korean hemi-sectioned heads were dissected macroscopically and microscopically
      from a clinical viewpoint. On the 32 tracings on the radiograph, the average
      distance between the retromolar portion and the LN was 7.8 mm, and no case was
      found where the LN ran above the alveolar crest as passing along the mandibular
      lingual plate. The bifurcation of the LN and IAN was located around the
      mandibular notch, inferior to the otic ganglion in 66% of the cases, and a
      plexiform branching pattern of the mandibular nerve was observed in only two
      cases. The bifurcation spot of the LN and IAN was located 14.3 mm inferior to the
      foramen ovale and 16.5 mm superior to the tip of hamulus. Collateral nerve twigs
      from the LN to the retromolar area were observed in 26 cases (81.2%), with an
      average of one nerve twig. We observed four types of variations in terms of
      communication pattern. In four specimens, the mylohyoid nerve passed through the
      mylohyoid muscle and connected with the LN. In other four specimens, the IAN
      communicated with the auriculotemporal nerve. We also observed another type of
      variational communication between the IAN and the nerve to the lateral pterygoid
      (LPt); this was observed in only one specimen, and it could be predicted that
      motor innervation from the nerve to the LPt was transmitted via the mental nerve
      to the depressor anguli oris. Another type was observed where the IAN divided
      into two branches with the posterior branch being partially entrapped by the LPt
      muscle fibers.

PMID- 14586563
TI  - An anatomical study of the levator veli palatini and superior constrictor with
      special reference to their nerve supply.
AB  - We dissected 50 head halves of 25 Japanese cadavers (10 males, 15 females) to
      investigate the innervations of the levator veli palatini (LVP) and superior
      constrictor pharyngis. The branches supplying the LVP were classified into the
      following three types according to their origins: supplying branches that
      originated from the pharyngeal branch of the glossopharyngeal nerve (type I, four
      sides, 8%), branches that originated from a communicating branch between the
      pharyngeal branches of the glossopharyngeal and vagus nerves (type II, 36 sides,
      72%), and those that originated from the pharyngeal branch of the vagus nerve
      (type III, 10 sides, 20%). In previous studies, supplying branches of type I were
      seldom described. Regarding the innervation of the superior constrictor, some
      variations were observed, and we consider it likely that there is a close
      relationship between these variations and the type of innervation of the LVP.

PMID- 14586564
TI  - Anatomical study on the morphology and blood supply of the falciform ligament and
      its clinical significance.
AB  - The purpose of this study was to understand the clinical significance of the
      morphology and blood supply of the falciform ligament in laparoscopic surgery.
      The structure, blood vessel distribution and anastomoses of the falciform
      ligament were observed in 20 cases of living laparoscopy, 30 cadaveric specimens
      injected with latex and five cadaveric specimens with Indian ink and hyaline. The
      falciform ligament was formed by two sides of peritoneum and its length, largest
      and smallest width were 8.3+/-1.6 cm, 4.9+/-0.8 cm and 1.1+/-0.3 cm,
      respectively. The left inferior phrenic artery and middle segment artery of the
      liver formed a vessel that arched and gave off 6-12 branches to the falciform
      ligament. The veins of the falciform ligament drained into the left inferior
      phrenic vein, and were not accompanied by any artery. In conclusion, the vessels
      of the falciform ligament anastomose with multiple vessels and form a significant
      pathway of the collateral circulation in the liver. The falciform ligament is an
      important landmark in laparoscopic surgery.

PMID- 14586565
TI  - Thoracotomy for pulmonary metastases.

PMID- 14586569
TI  - Superior performance of a paraaortic counterpulsation device compared to the
      intraaortic balloon pump.
AB  - The purpose of this study was to compare the hemodynamic effectiveness of a 30-ml
      stroke volume paraaortic counterpulsation device (PACD), presenting the
      advantages of ease of implantation and driving by a standard intraaortic balloon
      pump (IABP) console (Datascope 96, Datascope Corp., Montvale, NJ, USA) to that of
      a 40-ml IABP, in the setting of experimental heart failure. In an acute heart
      failure model, the IABP was placed in the descending aorta and the PACD in the
      ascending aorta of eight pigs. Both devices were driven by the same system, and
      hemodynamic measurements were obtained with and without mechanical assistance.
      The two pumps significantly reduced the systolic and end-diastolic aortic
      pressures, but the PACD reduced the latter more effectively (42.6 +/- 18.1% vs
      11.0 +/- 9.9%, p = 0.0001). Both pumps provided significant aortic diastolic
      augmentation, but the counterpulsation wave of the PACD was significantly greater
      (augmentation of 44.8 +/- 22.2% vs 37.6 +/- 15.6%, p = 0.031). Both lowered the
      end-diastolic left ventricular pressure with a trend toward PACD superiority
      (24.2 +/- 13.7% vs 19.7 +/- 13.5%, p = 0.064). It is concluded that the PACD,
      even with smaller stroke volume, is more effective than the IABP. The simplicity
      of its implantation, together with the ability of the standard IABP consoles to
      control its function, make it a promising device for mechanical assistance of the
      failing heart.

PMID- 14586570
TI  - Superficial spreading type colorectal tumors.

PMID- 14586571
TI  - Functional comparison between uncemented Austin-Moore hemiarthroplasty and
      osteosynthesis with three screws in displaced femoral neck fractures--a matched
      pair study of 168 patients.
AB  - There is no consensus as to whether osteosynthesis (OS) or hemiarthroplasty (HA)
      should be used as the primary treatment of displaced femoral-neck fracture. In a
      prospective matched-pair study, we compared 84 patients treated with OS with
      three screws and 84 patients treated with uncemented Austin-Moore HA focusing on
      functional parameters, reoperations and mortality. At 4 months after the
      fracture, functional recovery was not significantly different between the study
      groups. However, OS patients tended to have slightly better functional ability
      than HA patients, as more of them were able to walk out of doors (45.2% versus
      39.2%), more were able to walk without walking aids (23.7% versus 16.7%), and
      more returned to live in their own homes (80%versus 72.9%). OS patients used
      slightly but not significantly less painkillers and had less hip pain than HA
      patients. OS patients had had 15.4% more reoperations by 4 months and 14.2% more
      by 1 year compared to the HA group. The 4-month and 1-year mortality rates of the
      study groups were of the same order. Functional recovery was slightly better
      after OS with three screws than after uncemented HA, although no significant
      differences were seen in a sample of this size. On the other hand, OS was
      associated with a higher reoperation rate.

PMID- 14586574
TI  - Dedifferentiated chondrosarcoma of the appendicular skeleton: MRI-pathological
      correlation.
AB  - OBJECTIVE: To correlate the T2-weighted and STIR MRI appearances of
      dedifferentiated appendicular chondrosarcoma with gross and microscopic
      pathology. DESIGN AND PATIENTS: Nine patients with a histologically confirmed
      diagnosis of dedifferentiated appendicular chondrosarcoma were identified from
      the Bone Tumour Registry. All patients underwent MRI, including T2-weighted
      and/or STIR sequences in at least one plane, prior to limb salvage surgery. Areas
      of reduced signal intensity (SI) compared with hyperintense chondral tumour on
      the T2-weighted or STIR images were correlated with the resection specimen, to
      determine the relationship of such out areas of reduced SI with regions of
      dedifferentiation. RESULTS AND CONCLUSIONS: Patients presented over a period of 7
      years. There were five men and four women with mean age 68.2 years and age range
      51-78 years. Tumours arose in the femur (6 cases), humerus (2 cases) and tibia (1
      case). Three MRI patterns were identified: (1) type 1, a lesion with two distinct
      signal characteristics-hyperintense chondral and reduced SI dedifferentiated
      tumour (n=6); type 2, mainly reduced SI lesion-dedifferentiated tumour, with
      areas of signal void corresponding to matrix calcification (n=2); type 3, a
      heterogeneous lesion with no radiological evidence of underlying chondral tumour
      (n=1). T2-weighted or STIR MR sequences can identify areas of dedifferentiation,
      which should be the preferential site of pre-operative biopsy.

PMID- 14586575
TI  - Unilateral hypertrophy of tensor fascia lata: a soft tissue tumor simulator.
AB  - OBJECTIVE: To describe the imaging findings in eight cases of unilateral tensor
      fascia lata (TFL) hypertrophy presenting as soft tissue masses. DESIGN: Imaging
      studies and medical charts of eight patients were reviewed retrospectively. The
      imaging studies included five radiographs, five computed tomography (CT) and six
      magnetic resonance imaging (MRI) examinations. RESULTS: The majority of patients
      (seven of eight) presented with a palpable proximal anterior thigh mass. One
      patient was asymptomatic and incidentally diagnosed. There were six females and
      two males. Ages ranged from 27 to 86 years old (mean 61). MRI and CT showed
      unilateral enlargement of the TFL muscle in all cases. CONCLUSION: TFL muscle
      hypertrophy is an uncommon clinical entity, which can simulate a soft tissue
      tumor. The characteristic appearance on CT or MRI allows a confident diagnosis of
      muscle hypertrophy to be made, avoiding unnecessary biopsy or surgical
      intervention.

PMID- 14586576
TI  - Biochemical properties and substrate specificities of alkaline and histidine acid
      phytases.
AB  - Phytases are a special class of phosphatase that catalyze the sequential
      hydrolysis of phytate to less-phosphorylated myo-inositol derivatives and
      inorganic phosphate. Phytases are added to animal feedstuff to reduce phosphate
      pollution in the environment, since monogastric animals such as pigs, poultry,
      and fish are unable to metabolize phytate. Based on biochemical properties and
      amino acid sequence alignment, phytases can be categorized into two major
      classes, the histidine acid phytases and the alkaline phytases. The histidine
      acid phosphatase class shows broad substrate specificity and hydrolyzes metal
      free phytate at the acidic pH range and produces myo-inositol monophosphate as
      the final product. In contrast, the alkaline phytase class exhibits strict
      substrate specificity for the calcium-phytate complex and produces myo-inositol
      trisphosphate as the final product. This review describes recent findings that
      present novel viewpoints concerning the molecular basis of phytase
      classification.

PMID- 14586577
TI  - Production of isoamyl acetate in ackA-pta and/or ldh mutants of Escherichia coli
      with overexpression of yeast ATF2.
AB  - The gene coding for alcohol acetyltransferase ( ATF2), which catalyzes the
      esterification of isoamyl alcohol and acetyl coenzyme A (acetyl-CoA), was cloned
      from Saccharomyces cerevisiae and expressed in Escherichia coli. This genetically
      engineered strain of E. coli produced the ester isoamyl acetate when isoamyl
      alcohol was added externally to the cell culture medium. Various competing
      pathways at the acetyl-CoA node were inactivated to increase the intracellular
      acetyl-CoA pool and divert more carbon flux to the ester synthesis pathway.
      Several strains with deletions in the ackA-pta and/or ldh pathways and bearing
      the ATF2 on a high-copy-number plasmid were constructed and studied. Compared to
      the wild-type, ackA-pta and nuo mutants produced higher amounts of ester and an
      ackA-pta-ldh-nuo mutant lower amounts. Isoamyl acetate production correlated well
      with intracellular coenzyme A (CoA) and acetyl-CoA levels. The ackA-pta-nuo
      mutant had the highest intracellular CoA/acetyl-CoA level and hence produced the
      highest amount of ester (1.75 mM) during the growth phase under oxic conditions
      and during the production phase under anoxic conditions.

PMID- 14586578
TI  - Production of lipid compounds in the yeast Saccharomyces cerevisiae.
AB  - This review describes progress using the yeast Saccharomyces cerevisiae as a
      model organism for the fast and efficient analysis of genes and enzyme activities
      involved in the lipid biosynthetic pathways of several donor organisms.
      Furthermore, we assess the impact of baker's yeast on the production of novel,
      high-value lipid compounds. Yeast can be genetically modified to produce selected
      substances in relatively high amounts. A major advantage in choosing yeast as an
      object for metabolic engineering is the fact that the lipid pathways in this
      organism have been described in detail and are well characterized. We focus on
      the de novo production of three major families of lipid products. These are: (1)
      sterols, providing some previously known and some novel applications as examples
      of the lipid pathway enhancement that occurs naturally in yeast, (2) the
      reconstitution of the biosynthetic pathway of steroid hormones and (3) the
      biosynthesis of polyunsaturated fatty acids, leading to the biosynthesis of
      different omega-3 and omega-6 fatty acids which do not occur naturally in yeast.
      We utilize the current knowledge and point out perspectives and problems for
      future biotechnological applications in the field of lipid compounds.

PMID- 14586579
TI  - Metabolic engineering of Escherichia coli: construction of an efficient
      biocatalyst for D-mannitol formation in a whole-cell biotransformation.
AB  - A whole-cell biotransformation system for the conversion of d-fructose to d
      mannitol was developed in Escherichia coli by constructing a recombinant
      oxidation/reduction cycle. First, the mdh gene, encoding mannitol dehydrogenase
      of Leuconostoc pseudomesenteroides ATCC 12291 (MDH), was expressed, effecting
      strong catalytic activity of an NADH-dependent reduction of D-fructose to D
      mannitol in cell extracts of the recombinant E. coli strain. By contrast whole
      cells of the strain were unable to produce D-mannitol from D-fructose. To provide
      a source of reduction equivalents needed for d-fructose reduction, the fdh gene
      from Mycobacterium vaccae N10 (FDH), encoding formate dehydrogenase, was
      functionally co-expressed. FDH generates the NADH used for d-fructose reduction
      by dehydrogenation of formate to carbon dioxide. These recombinant E. coli cells
      were able to form D-mannitol from D-fructose in a low but significant quantity
      (15 mM). The introduction of a further gene, encoding the glucose facilitator
      protein of Zymomonas mobilis (GLF), allowed the cells to efficiently take up D
      fructose, without simultaneous phosphorylation. Resting cells of this E. coli
      strain (3 g cell dry weight/l) produced 216 mM D-mannitol in 17 h. Due to
      equimolar formation of sodium hydroxide during NAD(+)-dependent oxidation of
      sodium formate to carbon dioxide, the pH value of the buffered biotransformation
      system increased by one pH unit within 2 h. Biotransformations conducted under pH
      control by formic-acid addition yielded d-mannitol at a concentration of 362 mM
      within 8 h. The yield Y(D-mannitol/D-fructose) was 84 mol%. These results show
      that the recombinant strain of E. coli can be utilized as an efficient
      biocatalyst for d-mannitol formation.

PMID- 14586580
TI  - Initial stages of microbiologically influenced tarnishing on titanium after 20
      months of immersion in freshwater.
AB  - This paper studies the initial stages of iridescent tarnishes on titanium heat
      exchanger tubes in contact with running freshwater on the river Tagus in Spain
      for up to 20 months. Electrochemical impedance spectroscopy (EIS), scanning
      electron microscopy [(SEM with energy dispersive X-ray (EDX)] and X-ray
      photoelectron spectroscopy (XPS) in conjunction with argon-ion sputtering were
      the techniques used. The EIS data indicated a capacitive behavior, showing a
      semicircle that was better defined as the experimental time increased, indicating
      a decreasing tarnishing resistance of titanium. XPS and EDX results indicated
      that the main elements identified were calcium, phosphorus, nitrogen, and iron.
      The amount of these elements was higher on the tarnished titanium specimens than
      on the untarnished specimens. SEM analysis showed the presence of diatoms in the
      iridescent tarnishes on titanium tubes.

PMID- 14586581
TI  - Isolation of phages infecting Actinoplanes SN223 and characterization of two of
      these viruses.
AB  - Phages infecting the industrially important Actinoplanes strain SN223 were
      isolated from soil samples collected at the shores of inland waters in Germany.
      The genome sizes range from 53 kb to 58 kb. Preliminary analyses revealed G+C
      contents comparable with the G/C bias of the host. Electron microscopy of three
      selected viruses displayed no obvious morphological differences, the phage heads
      being icosahedral and their tails non-contractible. Two of the phages (phiAsp2,
      phiAsp3.1) characterized in more detail are capable of provoking putative
      pseudolysogenic growth of the host bacterium. The carrier state for phiAsp2, in
      which cells are tightly packed with viruses, was demonstrated by electron
      microscopy. The latter phage is apparently widely distributed, as it was isolated
      from regions which are distantly located, i.e. more than 600 km apart from each
      other.

PMID- 14586582
TI  - Purification and partial characterization of the Pyrococcus horikoshii
      methylmalonyl-CoA epimerase.
AB  - Methylmalonyl-CoA epimerase (MCE) from the hyperthermophilic archaeon, Pyrococcus
      horikoshii, was expressed at high levels in Escherichia coli, purified, and
      partially characterized. The P. horikoshii MCE enzyme was a homodimer with an
      apparent molecular mass of 31,700 Da. The K(m) of the enzyme for methylmalonyl
      CoA was 79 microM and the k(cat) was 240 s(-1). The P. horikoshii enzyme was
      extremely heat-stable and withstood boiling for 60 min without detectable loss in
      activity.

PMID- 14586583
TI  - Effects of the ventilation pattern and pulmonary blood flow on lung heat
      transfer.
AB  - To investigate the relative role of pulmonary perfusion compared to ventilation
      on lung heat exchange, we determined the effects of blood flow, tidal volume and
      frequency of ventilation on the rate of lung heat transfer. In anesthetized dogs
      and isolated, perfused lungs, we investigated the dependence of the overall lung
      heat transfer coefficient (HTC) and lung thermal capacitance upon ventilation and
      pulmonary blood flow. The relationship between the HTC and pulmonary blood flow
      was strongly dependent on ventilation parameters. A distributed model of non
      steady-state heat exchange adequately described these observations and
      demonstrated that changes in pulmonary blood flow may be considered as changes in
      the effective conductivity of the bronchial walls as 0.4 (0.1) J s(-1)m(-1) K(-1)
      per (l/min(-1)) of pulmonary blood flow. Our model describes the complex
      relationship between HTC, ventilation pattern, and effective thermal conductivity
      of the bronchial walls, all of which present limitations for the use of lung heat
      transfer to determine pulmonary blood flow.

PMID- 14586584
TI  - Long-term spinal cord injury increases susceptibility to isometric contraction
      induced muscle injury.
AB  - Complete spinal cord injury (SCI) results in inactivation and unloading of
      affected skeletal muscles. Unloading causes an increased susceptibility of muscle
      to contraction-induced injury. This study used magnetic resonance imaging (MRI)
      to test the hypothesis that isometric contractions would evoke greater muscle
      damage to the quadriceps femoris muscle (mQF) of SCI subjects than that of able
      bodied (AB) controls. MR images were taken of the mQF prior to, immediately post,
      and 3 days post electromyostimulation (EMS). EMS consisted of five sets of ten
      isometric contractions (2 s on/6 s off, 1 min between sets) followed by another
      three sets of ten isometric contractions (1 s on/1 s off, 30 s between sets).
      Average muscle cross-sectional area (CSA) and the relative areas of stimulated
      and injured muscle were obtained from MR images by quantifying the number of
      pixels with an elevated T2 signal. SCI subjects had significantly greater
      relative area [90 (2)% versus 66 (4)%, P<0.05; mean (SE)] but a lesser absolute
      area [16 (3) cm(2) versus 44 (6) cm(2), P<0.05] of mQF stimulated than AB
      controls. During EMS, peak torque was reduced by 66% and 37% for SCI and control
      subjects, respectively. Three days post EMS, there was a greater relative area of
      stimulated mQF injured for the SCI subjects [25 (6)% versus 2 (1)%, P<0.05]. Peak
      torque remained decreased by 22% on day 3 in the SCI group only. These results
      indicate that affected muscle years after SCI is more susceptible to contraction
      induced muscle damage, as determined by MRI, compared to AB controls. They also
      support the contention that electrically elicited isometric contractions are
      sufficient to cause muscle damage after a prolonged period of inactivity.

PMID- 14586586
TI  - Knee and ankle range of motion during stepping down in elderly compared to young
      men.
AB  - A major factor limiting mobility in elderly subjects is their difficulty with
      descending steps but the physiological and biomechanical basis of this problem is
      not well understood. To address this question we have compared the kinematics of
      stepping down in six elderly male subjects and six weight- and height-matched
      younger subjects. Five reflective markers were positioned on the lower limbs and
      subjects were filmed stepping down from four heights (200, 250, 300, and 335 mm).
      Maximum angular displacements for the knee and ankle of the supporting limb were
      expressed as a percentage of each subject's passive range of motion (ROM). Time
      spent in 'foot flat' during single support was also compared. The results show
      the elderly subjects sustained dorsiflexion and a 'foot flat' position of the
      support limb for a significantly ( P<0.05) longer period than the young
      (approximately 20%). Consequently, elderly subjects utilised a greater percentage
      of their passive ankle ROM compared to the young (elderly approximately 200%;
      young approximately 125%). We conclude that the elderly maintained a 'foot flat'
      position for a longer period possibly to increase the time spent on a larger base
      of support. These results suggest that exercise prescription in the elderly
      should include stretching in order to increase the ROM at the ankle joint.

PMID- 14586585
TI  - Effect of low oxygen inhalation on changes in blood pH, lactate, and ammonia due
      to exercise.
AB  - The present study examined the effect of hypoxia-induced respiratory alkalosis on
      exercise-induced metabolic acidosis and increases in plasma lactate and ammonia
      levels. Six male subjects underwent exercise of increasing intensity until
      exhaustion: (1) in normoxia (20.9% O(2)) (=MAX), (2) in hypoxia (12% O(2)) (=HP)
      in which hypoxic condition had been maintained from 60 min before to 30 min after
      exercise, and (3) the same intensity of exercise as HP in normoxia (=SUB).
      Arterialized blood was drawn from a superficial vein. Post-exercise blood pH was
      significantly higher in HP than in MAX ( P<0.05), although plasma lactate was at
      the same level. For hypoxia as compared to normoxia, regression analysis
      confirmed a parallel shift of plasma lactate to higher pH levels indicating the
      effect of respiratory alkalosis ( P<0.01). After exercise plasma levels of
      ammonia were lower in HP than in MAX ( P<0.05). Regression analysis between
      ammonia and pH revealed nearly identical changes in hypoxia and normoxia at low
      pH. From these results, we conclude that: (1) hypoxia-induced respiratory
      alkalosis attenuated exhaustive exercise-induced metabolic acidosis, (2) plasma
      lactate concentration was determined by the relative exercise intensity, (3) the
      maximum plasma ammonia concentration under exhaustive exercise was reduced at
      hypoxia because of respiratory alkalosis.

PMID- 14586587
TI  - The critical power model for intermittent exercise.
AB  - This paper develops and illustrates the critical power model for intermittent
      work. Model theoretic development reveals that total endurance time is always a
      step function of one or more of the four independent variables: work interval
      power output ( P(w)), rest interval power output ( P(r)), work interval duration
      ( t(w)), and rest interval duration ( t(r)). Six endurance-trained male athletes
      recorded their best performances during the season in 3-, 5-, and 10-km races,
      and performed three different intermittent running tests to exhaustion in random
      order, recording their total endurance times. These data were used to illustrate
      the model and compare anaerobic distance capacities (alpha) and critical
      velocities (beta) estimated from each type of exercise. Good fits of the model to
      data were obtained in all cases: 0.954< R(2)<0.999. Critical velocity was found
      to be significantly less when estimated using an intermittent versus continuous
      running protocol.

PMID- 14586588
TI  - A chamber-experiment investigation of the interaction between perceptions of
      noise and odor in humans.
AB  - OBJECTIVES: This study was designed to investigate human comfort and health
      effects following exposure to noise and odor and to explore the interaction
      between perceptions of noise and odor in humans. MATERIALS AND METHODS: Nine
      healthy subjects were randomly exposed to noise, odor, and their combination, in
      a 3 x 3 Latin square design for 80 min in an exposure chamber. Continuous noise
      was broadcast at an average level of 75 dBA by a loudspeaker, and odor was
      provided by furfurylmercaptan (a coffee-aroma constituent). A standardized 28
      item questionnaire, together with mood-scale ratings, nasal dimensions by
      acoustic rhinometry, addition tests for distraction, and skin humidity, were
      performed before and at the end of exposure. RESULTS: In the questionnaire
      investigation, the perceived "sound level" was significantly affected by noise
      and the combined exposures, while "odor intensity", "air quality", and "need more
      ventilation" was significantly affected by odor and the combined exposures.
      Perceptions of symptoms became worse with increasing exposure time, such as
      perceived "dry nose" and "sleepiness" by odor and combined exposures, "headache"
      by noise, "concentration difficulty", "general well being", and "stressed by
      being in the chamber" by noise, odor and combined exposures. In addition, the
      occurrence of interactions was analyzed by comparison of the ratings of perceived
      "sound level", "odor intensity", "air quality", and "need more ventilation"
      during the combined exposure with two single exposures. Insignificant interaction
      was found but it indicated a decreased tendency to perceptions of discomfort from
      "odor intensity", "air quality", and "need for more ventilation" when noise was
      added to odor exposure. CONCLUSION: It may be concluded that noise and odor cause
      discomfort in humans. Moreover, the study might indicate that additions of noise
      reduce (mask) the perception of discomfort from odor, and additions of odor have
      no or little affect on the perception of noise.

PMID- 14586589
TI  - Melanocortins applied intravitreally delay retinal dystrophy in Royal College of
      Surgeons rats.
AB  - BACKGROUND: Alpha-melanocyte-stimulating hormone (MSH) is a neurotrophic agent.
      In Royal College of Surgeons (RCS) rats, the effects of an MSH analog (MA) were
      investigated on: (1) the preservation of photoreceptors in vivo following MA
      intravitreal injection; (2) whether MA is a mitogenic factor. METHODS: The study
      comprised five RCS rat groups, two injected with different doses of MA, one
      injected with PBS, and two non-injected groups. A single injection of MA or PBS
      was applied intravitreally to RCS rats on postnatal day 20 (20p). Photoreceptor
      preservation on 40p was studied using light microscopy. Considering the mitogenic
      effect of MA, it was studied whether cell proliferation was induced by MA in
      cultured retinal pigment epithelium (RPE) using the thymidine uptake technique.
      RESULTS: In degenerating untreated RCS retinae the number of photoreceptor rows
      on 40p was 60-70% lower than on 20p. Retinae treated with higher doses of MA
      revealed on 40p a localized significant photoreceptor rescue in the retinal
      hemisphere which had been injected. However, only a small area of photoreceptor
      preservation was noted in the injected hemisphere in retinae treated with the
      lower MA dose. MA showed no mitogenic effect in endothelial or RPE cell culture
      in vitro. CONCLUSIONS: This study is the first to demonstrate that: (1)
      intravitreally injected MA promotes a dose-related localized rescue of
      photoreceptors in RCS retinae which may be related to the hormone's neurotrophic
      activity; (2) MA has no mitogenic or angiogenic properties; (3) MA, as a
      neuroprotective agent, might be considered for future treatment of retinal
      dystrophy.

PMID- 14586590
TI  - Reduction of experimental laser-induced choroidal neovascularization by orally
      administered BPHA, a selective metalloproteinase inhibitor.
AB  - BACKGROUND: N-Biphenyl sulfonyl-phenylalanine hydroxamic acid (BPHA), a
      synthetic, selective matrix metalloproteinase (MMP)-2, -9, -14 inhibitor, has
      been reported to show significant antiangiogenic activity without unpleasant
      adverse effects. After film in situ zymography (FIZ) and conventional zymography
      were performed to detect MMP in experimental choroidal neovascularizations
      (CNVs), we studied the reducible effect of BPHA on CNVs. METHODS: Using FIZ, the
      gelatinolytic activity of MMPand BPHA-reduction on gelatinolysis were examined in
      diode-laser-induced CNV lesions in a total of 22 male Brown Norway rats. The MMP
      subtypes were studied in the CNV lesions of three rats using conventional
      zymography. Vehicle solution only or 25-, 50-, or 100 mg/kg-body-weight of BPHA
      was administered orally twice daily for 14 days after the laser photocoagulation
      in 18 rats, respectively. Fluorescein angiograms were taken, and the late
      hyperfluorescence of CNVs was given scores by three researchers using four
      grades. The thickness of CNV lesions was studied histologically. RESULTS: In
      laser-induced CNVs, the gelatinolytic activity of MMP and reduction of
      gelatinolysis by BPHA were observed on FIZ, and MMP-2 and proMMP-2 were
      identified by conventional zymography. The scores given to the late dye leakage
      and staining on angiograms were lower in the BPHA-treated groups ( p<0.01) than
      in the controls, and the effect appeared to be dose-dependent. Similarly, the CNV
      lesions in the BPHA-treated groups were less thick than in the controls (
      p<0.01). CONCLUSIONS: MMP-2 played a role in laser-induced CNV development, and
      administration of BPHA reduced the experimental CNVs.

PMID- 14586592
TI  - Characteristics of spontaneous eyeblink activity during video display terminal
      use in healthy volunteers.
AB  - PURPOSE: To analyse the spontaneous eyeblink rate (SEBR) and inter-eyeblink
      intervals (IEBI) of normal volunteers before and during video display terminal
      (VDT) use. METHODS: The SEBR of 51 normal volunteers was measured by counting the
      absence of the corneal reflex using a computer-based video analysis system. Only
      complete eyeblinks were recorded within 10 min under three different conditions:
      during a conversation, during VDT use without corneal anaesthesia, and during VDT
      use with corneal anaesthesia. The IEBI (in seconds) were determined to study
      individual time-dependent changes of SEBR. RESULTS: In comparison with SEBR
      during conversation (mean 15.54 eyeblinks/min, standard deviation +/-13.74
      eyeblinks/min) the SEBR decreased significantly during VDT use without corneal
      anaesthesia (5.34 +/- 4.53 eyeblinks/min). Corneal anaesthesia further
      significantly reduced SEBR (2.78 +/- 2.77 eyeblinks/min). The SEBR was
      characterized by marked interindividual variability, ranging between 11 and 664
      eyeblinks/10 min during conversation, between 4 and 189 eyeblinks during VDT use
      without corneal anaesthesia and between 1 and 119 eyeblinks at VDT use with
      corneal anaesthesia. No significant correlation between SEBR (during conversation
      or during VDT use) and quality (break-up time) or quantity (Schirmer I test,
      Jones test) of the tear film could be detected. Evaluation of the IEBI revealed
      three different types of eyeblink pattern during VDT use without corneal
      anaesthesia. Type 1 was characterized by a very low SEBR (0-2 eyeblinks/min) and
      relatively homogeneous distribution of eyeblinks, type 2 showed a moderate SEBR
      (1.2-8.5 eyeblinks/min) including three further subtypes. Type 3 was
      characterized by a high SEBR (6.8-18.9 eyeblinks/min) of regular or irregular
      pattern. CONCLUSIONS: VDT use is associated with a profound decrease of the SEBR
      in healthy subjects. There are marked interindividual differences in SEBR and no
      correlation between the SEBR and ocular tear film parameters in normal eyes. The
      SEBR is further reduced by corneal anaesthesia. The presence of different
      patterns of eyeblinking may be related to various exogenous and endogenous
      factors and may lead to a better understanding of ocular reactions during VDT
      use.

PMID- 14586593
TI  - The clinical expression of primary dystonia.
AB  - Dystonia (from the Greek, "altered muscle tone") refers to sustained and vigorous
      contractions forcing a body region into an abnormal position that is consistently
      present. Dystonic postures and movements can variably combine to produce a wide
      spectrum of clinical presentations. The movement can affect one, two or more body
      regions, as in focal, segmental or generalised dystonia. Dystonia arising in
      childhood tends to progress to a generalised form; adult-onset dystonia, instead,
      is often focal or segmental. Dystonic movements have specific features that can
      be recognised by clinical observation, such as speed, consistency,
      predictability, variability and relationship with voluntary movement. Sensory
      tricks and gestes antagonistes are manoeuvres that specifically alleviate
      dystonic movements and postures thereby providing diagnostic clues. The diagnosis
      of primary dystonia requires the observation of a consistent clinical picture.

PMID- 14586591
TI  - Cathepsin B in the rat eye.
AB  - BACKGROUND: Cathepsin B is a mammalian cysteine protease. The enzyme has been
      suggested to participate in the patophysiological processes of keratoconus as
      well as in the corneal response to infectious agents. This study describes the
      localization of cathepsin B in the rat eye. METHODS: Cathepsin B was identified
      in rat ocular tissues by Western blotting and immunohistochemistry. Cathepsin B
      mRNA levels were analyzed in the tissues by quantitative real-time cDNA
      amplification (QRT-PCR). RESULTS: Cathepsin B is present in the epithelium, in
      stromal cells and in the endothelium of the cornea. It is also present in the
      epithelium lining the ciliary processes, in occasional stromal cells in the iris,
      in the anterior subcapsular lens epithelium and in various cell types in the
      retina. At all locations cathepsin B is present in cytoplasmic granules,
      presumably lysosomes. QRT-PCR analysis detected cathepsin B mRNA in all these
      tissues in amounts correlating to the immunodetection results, suggesting that
      the enzyme detected is locally produced. CONCLUSIONS: Cathepsin B is present in
      several tissues and cell types throughout the rat eye. It is localized to
      cytoplasmic granules, presumably lysosomes. Our results suggest that it is
      probably also produced in the same cell types.

PMID- 14586594
TI  - Neurophysiological studies of pain pathways in peripheral and central nervous
      system disorders.
AB  - Standard clinical neurophysiological assessment of somatosensory pathways by
      sensory evoked potentials (SEPs) is limited to the tactile and proprioceptive
      systems consisting of large fibers in the peripheral nerve, the dorsal columns of
      the spinal cord and the medial lemniscus in the brainstem. This limitation means
      that about half of the lesions in the somatosensory system will not be
      detectable. In recent years, many clinical studies have confirmed that laser
      evoked potentials (LEPs) allow the assessment of the other half of the
      somatosensory system. Rapid heating of the skin by infrared laser pulses
      specifically activates the nociceptive and thermoreceptive pathways consisting of
      small fibers in the peripheral nerve and the anterolateral spinothalamic tract in
      the spinal cord and brainstem. Owing to the large degree of convergence of the
      somatosensory pathways on to common thalamic nuclei, the differential use of LEP
      vs. SEP is less evident for thalamocortical lesions. In contrast to standard
      SEPs, the LEP technique can be applied to non-glabrous skin in any dermatome.
      This review summarizes the principles of clinical neurophysiological studies of
      pain pathways and the findings obtained in patients with peripheral and central
      nervous system disorders. These data provide a rational basis for developing
      clinical indications for LEP testing.

PMID- 14586595
TI  - A disease-specific psychosocial questionnaire for Parkinson's disease caregivers.
AB  - OBJECTIVE: To evaluate the "Belastungsfragebogen Parkinson Angehorigen
      kurzversion" (BELA-A-k), a questionnaire for measuring psychosocial problems and
      need for help in Parkinson's disease (PD) caregivers. METHODS: The
      "Belastungsfragebogen Parkinson Angehorigen-kurzversion" was translated into
      Dutch. It consists of 15 items with a "Bothered by" (Bb) and a "Need for Help"
      (NfH) score. The BELA-A-k was tested for cultural differences, relevance and
      feasibility in a pilot (n = 10). We determined the psychometric properties in a
      validation study (n = 50) and compared the BELA-A-k with the Sickness Impact
      Profile, the COOP/WONCA Functional Health Assessment Charts and the Loneliness
      Questionnaire (de Jong-Gierveld). All questionnaires were administered in person
      at home, in a prescribed order. RESULTS: The BELA-A-k was completed by 60 PD
      caregivers. The internal-consistency reliability coefficients for the total
      "Bothered by" (0.90) and "Need for Help" (0.92) scales were excellent. The
      internal consistency of the subscales exceeded the 0.70 standard except for the
      "Bothered by" and "Need for Help" Social functioning scale (Bb = 0.62; NfH =
      0.65) and the Partner-bonding/Family scale (NfH = 0.69). Almost all BELA-A-k
      subscales correlated highly (P < 0.001) with the corresponding scales of the
      standard quality of life indices. CONCLUSION: The BELA-A-k is a relevant,
      reliable and valid measure for assessing psychosocial problems and need for help
      of PD-caregivers.

PMID- 14586596
TI  - MR evidence of structural and metabolic changes in brains of patients with
      Werner's syndrome.
AB  - OBJECTIVE: To assess CNS abnormalities in patients with Werner's syndrome (WS)
      using MR metrics specific for tissue damage. BACKGROUND: WS is a rare autosomal
      recessive disorder that causes premature aging. The CNS involvement in this
      disease is still debated. METHODS: Two siblings who showed signs of neurological
      involvement underwent MR spectroscopic imaging (MRSI) and magnetization transfer
      (MT) imaging. Also, on conventional T1-weighted MR images, measurements of total
      brain volume were performed. RESULTS: Conventional MR images of both WS patients
      did not show abnormalities on visual inspection. However, both WS patients showed
      significantly lower values of normalized total brain volume and MT ratio in the
      white matter than age-matched normal controls. Also, proton MRSI showed
      significantly lower values of central brain NAA/Cr in WS patients than in normal
      controls. CONCLUSIONS: Our findings suggest that, despite normal appearance on
      conventional MRI, diffuse structural and metabolic tissue damage can be
      demonstrated in WS brains by means of sensitive MR methods even in patients with
      moderate or subclinical CNS involvement.

PMID- 14586597
TI  - Neurological complications of Werner's syndrome.
AB  - Patients with Werner's syndrome have the appearance of premature ageing.
      Neurological complications are usually regarded as uncommon. The neurological
      manifestations in three patients with cardinal features of Werner's syndrome,
      including short stature, premature greying and baldness, thin arms and legs,
      cataracts and scleroderma-like skin changes, are presented. The neurological
      features included transient ischaemic attacks secondary to atherosclerosis in the
      common carotid arteries (one patient), sensory peripheral neuropathy (one
      patient) and peripheral neuropathy with a possible myelopathy (one patient). In
      one of these patients the diagnosis of Werner's syndrome was not recognised prior
      to neurological referral. Although neurological disease in patients with Werner's
      syndrome is uncommon, it may be under-recognised. Some of the neurological
      complications are secondary to premature cerebrovascular disease, but the
      pathogenesis of peripheral neuropathy and myelopathy in patients with Werner's
      syndrome is uncertain.

PMID- 14586598
TI  - Cervical artery dissection--clinical features, risk factors, therapy and outcome
      in 126 patients.
AB  - The highly variable clinical course of cervical artery dissections still poses a
      major challenge to the treating physician. This study was conducted (1) to
      describe the differences in clinical and angiographic presentation of patients
      with carotid and vertebral artery dissections (CAD, VAD), (2) to define the
      circumstances that are related to bilateral arterial dissections, and (3) to
      determine factors that predict a poor outcome. Retrospectively and by
      standardised interview, we studied 126 patients with cervical artery dissections.
      Preceding traumata, vascular risk factors, presenting local and ischemic
      symptoms, and patient-outcome were evaluated. Patients with CAD presented more
      often with a partial Horner's syndrome and had a higher prevalence of
      fibromuscular dysplasia than patients with VAD. Patients with VAD complained more
      often of neck pain, more frequently reported a preceding chiropractic
      manipulation and had a higher incidence of bilateral dissections than patients
      with CAD. Bilateral VAD was significantly related to a preceding chiropractic
      manipulation. Multivariate analysis showed that the variables stroke and arterial
      occlusion were the only independent factors associated with a poor outcome. This
      study emphasises the potential dangers of chiropractic manipulation of the
      cervical spine. Probably owing to the systematic use of forceful neck-rotation to
      both sides, this treatment was significantly associated with bilateral VAD.
      Patients with dissection-related cervical artery occlusion had a significantly
      increased risk of suffering a disabling stroke.

PMID- 14586599
TI  - Feasibility study of single region lambda chart analysis for pyramidal tract
      physiology.
AB  - Diffusion characteristics of the pyramidal tract were assessed in nine patients
      who had clinical evidence of pyramidal tract dysfunction, utilizing lambda chart
      analysis (LCA). The underlying pathologic process of tract dysfunction was varied
      and included Pelizaeus-Merzbacher disease (PMD), Alexander disease,
      adrenoleukodystrophy (adrenomyeloneuropathy (AMD) type and cerebral type),
      amyotrophic lateral sclerosis (ALS), and Wallerian degeneration (WD). While
      pyramidal tract diffusion characteristics in WD indicated a pathological process
      characterized by replacement of normal fibers by smaller cellular component such
      as degenerated small fibers and/or gliosis, pyramidal tract diffusion
      characteristics in patients with PMD, Alexander disease, and adreno
      leukodystrophy of the cerebral type indicated a pathological process
      characterized by replacement of normal fibers by larger cellular components such
      as spheroids or edematous space. Pyramidal tract diffusion characteristics of
      patients with ALS or adrenoleukodystrophy of AMD type were relatively intact
      suggesting a pathological process characterized by relatively preserved
      structural architecture. These findings are highly consistent with known
      pathophysiological indices and indicate the feasibility of the clinical utility
      of LCA for assessing pyramidal tract physiology.

PMID- 14586600
TI  - Double-blind crossover study with dolasetron mesilate, a 5-HT3 receptor
      antagonist in cerebellar syndrome secondary to multiple sclerosis.
AB  - Cerebellar syndrome is one of the most disabling developments in multiple
      sclerosis (MS). In neurodegenerative disorders, cerebellar syndrome is thought to
      be related to a neurochemical deficit of 5-hydroxytryptamine (5-HT). Previous
      studies found that a levorotatory form of 5-hydroxytryptophan, a 5-HT precursor,
      and ondansetron, a 5-HT(3) receptor antagonist, decreased cerebellar symptoms in
      Friedreich's ataxia and MS. We studied the effect of another 5-HT(3) receptor
      antagonist, dolasetron mesilate, on cerebellar syndrome in MS patients.Thirty
      four MS patients were included in a placebo-controlled double-blind crossover
      study. They received a single dose of intravenous dolasetron mesilate or placebo.
      A quantitative evaluation of cerebellar syndrome using the nine-hole peg test and
      an ataxia score comprising static and kinetic parameters were performed before
      and after each treatment. No statistical difference was observed in the
      dolasetron mesilate group, compared with the placebo group. There was, however,
      inter-individual variability in the treatment response. This double-blind study
      on cerebellar syndrome in MS patients did not confirm the positive effect of
      dolasetron mesilate suggested by previous studies.

PMID- 14586601
TI  - Time course of the effect of a bolus dose of intrathecal baclofen on severe
      cerebral spasticity.
AB  - Continuous intrathecal administration of baclofen with implanted programmable
      pump systems is recommended in the treatment of severe spasticity of cerebral
      origin. Prior to pump implantation, a baclofen bolus test (BBT) is used to assess
      the effectiveness of intrathecal baclofen using clinical scales such as the
      Modified Ashworth Scale (MAS). In the literature, the time and period of maximum
      effect of a bolus dose of intrathecally administered baclofen in patients with
      cerebral spasticity is variously reported. The aim of the study was, therefore,
      to reveal the time course of the effect of a BBT on severe cerebral spasticity by
      the use of a recently described spasticity measurement method. Spasticity in knee
      joints of 13 patients with severe cerebral spasticity was repeatedly assessed
      using the MAS and also continuously recorded by the measurement of force under
      circular fibreglass casts. Force was recorded as nettorque by multiplying the
      force by the distance between sensor and joint axis, thus allowing inter
      individual comparison. Half-hour time integrals (TI) of net-torque were
      determined 9 hours before and 22 hours after intrathecal baclofen administration.
      Post-BBT half-hour time integrals (TI(+0), TI(+0.5), to TI(+22)) were compared
      with the mean of 17 pre-BBT half-hour time integrals. Significantly lower post
      BBT half-hour time integrals compared with were found between TI(+2) and TI(+8)
      (Dunnett adjusted p < 0.05). The median lowest TI after BBT of the 13 patients
      was TI(+4). The lowest mean MAS scores were found 4 hours after BBT. The findings
      suggest that the greatest effect of BBT on cerebral spasticity occurs between 2
      and 8.5 hours, with a maximal effect at 4 hours after intrathecal baclofen
      injection. Clinical scales used to determine the effect of BBT should thus be
      carried out during this period-ideally at 4 hours after baclofen injection.

PMID- 14586602
TI  - The effects of frequency in pallidal deep brain stimulation for primary dystonia.
AB  - The effect of stimulation frequency for pallidal deep brain stimulation in five
      patients with either generalized or segmental dystonia was evaluated three to
      twelve months postoperatively via a randomized, double-blind paradigm. The
      quality of life and the severity of dystonic symptoms improved by approximately
      60% and 43% respectively using a frequency of 130 Hz. Compared with 130 Hz a
      significant further clinical improvement was observed at frequencies of 180 and
      250 Hz, which contrasted with a significant deterioration at lower frequencies
      (5, 50 Hz) compared to 130 Hz.

PMID- 14586603
TI  - A randomized trial on the efficacy of intensive rehabilitation in the acute phase
      of ischemic stroke.
AB  - Sixty patients admitted to hospital for hemispherical ischemic stroke causing
      severe disabilities were enrolled in the study. The patients were divided in two
      groups: A and B. The patients in group A were given intensive rehabilitative
      treatment; those in group B were given ordinary rehabilitative treatment. Both
      treatments lasted 14 days. At the end of that period, the patients of both groups
      were sent to the same rehabilitation center to continue treatment, using the same
      methods for all. The patients were evaluated by means of the modified N. I. H.
      Stroke Scale and the Barthel-Index on the day of enrollment, on the 14(th) and
      180(th) day. The results obtained from intensive treatment were no better than
      those obtained from ordinary treatment. This study shows that there is no point
      in adopting an intensive rehabilitative treatment for an ischemic stroke in its
      acute phase: a more expensive and time-consuming effort does not in any way lead
      to a better outcome.

PMID- 14586605
TI  - Does neurorehabilitation have a role in relapsing-remitting multiple sclerosis?
AB  - Patients with relapsing-remitting multiple sclerosis (RR MS) often make
      incomplete recovery from disabling exacerbations, despite corticosteroid
      treatment. Inpatient rehabilitation has been shown to be valuable in progressive
      MS, but its role in RR MS is less clear. We evaluated the effect of
      rehabilitation in consecutive patients with RR MS admitted to a neurological
      rehabilitation unit. Outcome measures applied on admission and discharge included
      the Expanded Disability Status Scale (EDSS), the Barthel Index (BI) and the
      Functional Independence Measure (FIM), as well as a visual analogue scale (VAS)
      of the patients' perception of rehabilitation impact. Confounding factors
      including the timing of steroid therapy and re-admissions were also examined. RR
      patients showed considerable improvement following rehabilitation, with a median
      change of -0.5 on EDSS, +4 on BI and +12 on FIM (mean change of -0.8 EDSS, +4.5
      BI and +15.6 FIM points; effect sizes of -1.01, 0.97 and 0.86, respectively),
      which was significantly greater than other MS subtypes. RR patients rated their
      admissions highly (median VAS 8.9, interquartile range 7.5-9.9), and the VAS
      scores correlated modestly with disability measures (Spearman's rho = -0.42, 0.31
      and 0.24 versus EDSS, BI and FIM, respectively; p = 0.007-0.040). Repeat
      admissions and the timing of steroid treatment did not have a significant effect
      on outcome. This suggests that inpatient rehabilitation is useful in RR MS,
      particularly in patients with incomplete recovery from relapses who have
      accumulated moderate to severe disability.

PMID- 14586604
TI  - High incidence of SMN1 gene deletion in Moroccan adult-onset spinal muscular
      atrophy patients.
AB  - Spinal muscular atrophy (SMA) is an autosomal recessive motor neuropathy
      characterized by selective degeneration of anterior horn cells of the spinal
      cord. Childhood SMA is divided into three types (I-III) on the basis of age of
      onset and severity. These disorders have been linked to the 5q13 region, where
      mutations in the Survival Motor Neuron 1 (SMN1) gene have been found in affected
      individuals. In the case of adult-onset SMA (type IV), on the other hand, reports
      of homozygous absence of SMN1 gene have been rare. We conducted deletion analysis
      of SMN and a neighboring gene, NAIP (neuronal apoptosis inhibiting protein).
      Among 54SMA patients (types I-IV), all of Moroccan origin, Exon 7 of the SMN1
      gene was homozygously absent in 100% of type I, 90% of type II, 74% of type III
      and 80% of type IV SMA patients. Deletion of SMN1 exon 8 was detected in 100% of
      type I, 53% of type II, 53% of type III and 80% of type IV patients. NAIP exon 5
      was homozygously deleted in 67% of type I, 32% of type II, 5% of type III and 20%
      of type IV SMA patients. Thirty control individuals who were studied had normal
      SMN1 and NAIP genes. Our results show a high incidence of SMN1 gene deletion in
      adult-onset SMA patients indicating that SMN1 is the autosomal recessive adult
      SMA-causing gene. While NAIP is commonly deleted in SMA, this is unlikely to
      affect disease severity; it was deleted in two adult SMA patients with mild
      phenotypes.

PMID- 14586606
TI  - Chronic subthalamic nucleus stimulation and striatal D2 dopamine receptors in
      Parkinson's disease--A [(11)C]-raclopride PET study.
AB  - CONTEXT: Subthalamic nucleus (STN) stimulation mechanism of action remains a
      matter for debate. In animals, an increased striatal dopamine (DA) release due to
      STN stimulation has been reported. OBJECTIVE: To determine in Parkinson's disease
      (PD) patients using positron emission tomography (PET) and [11C]-Raclopride,
      whether STN stimulation induces a striatal DA release. METHODS: Nine PD patients
      with bilateral STN stimulation were enrolled and underwent two [11C]-Raclopride
      PET scans. The scans were randomly performed in off and on stimulation
      conditions. Striatal [11C]-Raclopride binding potential (BP) was calculated using
      regions of interest and statistical parametric mapping. RESULTS: For PD patients,
      the mean [(11C]-Raclopride BP (+/- SD) were, in Off stimulation condition: 1.7 +/
      0.3 for the right caudate nucleus, 1.8 +/- 0.4 for the left caudate nucleus, 2.6
      +/- 0.5 for the right putamenand 2.6 +/- 0.5 for the left putamen. In On
      stimulation condition: 1.7 +/- 0.4 for the right caudate nucleus, 1.9 +/- 0.5 for
      the left caudate nucleus, 2.8 +/- 0.7 for the right putamen and 2.7 +/- 0.8 for
      the left putamen. No significant difference of BP related to the stimulation was
      noted. CONCLUSION: STN stimulation does not produce significant variations of
      striatal DA release as assessed by PET and [11C]-Raclopride.

PMID- 14586607
TI  - Interferon-beta-1 b decreased matrix metalloproteinase-9 serum levels in primary
      progressive multiple sclerosis.
AB  - Recent reports have shown that matrix-metalloproteinases (MMPs) facilitate T-cell
      migration into the CNS and play a role in disruption of the blood-brain-barrier
      and myelin break-down. An increase of MMP-9 serum levels predicts disease
      activity in relapsing remitting multiple sclerosis (RRMS). Interferon-beta (IFN
      beta), which is an established treatment for RRMS, inhibits T-cell migration in
      vitro in parallel with the downregulation of MMP expression. Only limited data
      are available for primary progressive multiple sclerosis (PPMS) which differs in
      demographic and immunological aspects as well as in MRI criteria from RRMS. In
      this study, 19 patients with laboratory-supported definite PPMS were treated with
      8 x 10(6) IU IFN-beta1b (Betaferon) subcutaneously every other day. Serum was
      collected before treatment and on months 1, 2, 3, 6 and 9 during treatment.
      Levels of MMP-9 and of its natural inhibitor known as tissue-inhibitor of matrix
      metalloproteinase-1 (TIMP-1) were quantified by ELISA. In addition MMP-2 serum
      levels were determined by zymography. 19 healthy volunteers served as controls.
      Before treatment serum levels of MMP-9 were elevated in patients with PPMS
      compared with controls, whereas there was no difference in TIMP-1 serum levels.
      During treatment with IFN- beta1b the concentration of MMP-9 in the serum of 18
      out of 19 PPMS patients decreased,whereas serum levels of MMP-2 and TIMP-1
      remained nearly unaffected. Our results demonstrate that the MMP-9 to TIMP-1
      ratio in patients with PPMS is elevated in comparison with healthy controls. The
      suppression of MMP-9 by IFN-beta1b indicates that this drug is immunomodulatory
      active in PPMS patients. Further studies are necessary to test if IFN-beta exerts
      a beneficial effect in PPMS.

PMID- 14586608
TI  - Changes of percentages in immune cells phenotypes and cytokines production during
      two-year IFN-beta-1a treatment in multiple sclerosis patients.
AB  - OBJECTIVE: The aim of the study was to find out whether INF-beta-1a influences
      the immune profile of peripheral blood (PB) leukocytes in MS patients. METHOD: We
      have studied 20 patients with relapsing-remitting form of MS treated with INF
      beta-1a using twocolor cytometry. We determined immune cells phenotypes and
      production of some cytokines: IL-4, IL-10, IL-12, IFN-gamma, before drug
      administration and after starting the treatment. RESULTS: In MS patients an
      increased percentage of CD14(+)CD86(+) cells and CD3(+)CD25(+) cells was noticed
      after 6, 9 and 12 months of INF-beta-1a therapy. Among cytokine-producing cells
      we noted an increased fraction of CD3(+)IL-4, CD14(+)IL-10 and CD14(+)IL-12 cells
      after 12 months, which decreased to the level observed before treatment after 24
      month therapy. CONCLUSIONS: IFN-beta-1a treatment was associated with significant
      changes in immune response. This effect was mostly evident within the first year
      of treatment.

PMID- 14586609
TI  - Propofol in status epilepticus: little evidence, many dangers?
AB  - INTRODUCTION: Several guidelines recommend the use of propofol for the treatment
      of refractory status epilepticus. An increased mortality rate in high dose, long
      term treatment with propofol in adult patients was published recently. This
      prompted us to assess the literature on the scientific evidence for the efficacy
      and safety of propofol in the treatment of refractory status epilepticus.
      METHODS: Medline was searched and the three authors independently reviewed all
      Medline abstracts for selection of papers. RESULTS: We included 22 articles with
      original data on the use of propofol in refractory status epilepticus. Randomised
      clinical trials were lacking. Two non-randomised studies compared propofol with
      barbiturates and midazolam respectively. Both studies reported a higher risk of
      mortality for propofol. In addition, case reports and case series on the use of
      propofol as anaesthetic or sedative in children and adults reported several
      lethal cases. CONCLUSIONS: Serious doubts may be raised on the safety of propofol
      in the treatment of refractory status epilepticus. The two non-randomised studies
      and several case reports show an increased risk of mortality. Guidelines should
      not recommend the use of propofol as a routine treatment in refractory status
      epilepticus before a proper randomised trial has been performed.

PMID- 14586610
TI  - Review of the evidence for the use of propofol in the management of status
      epilepticus.

PMID- 14586611
TI  - A case of late-onset CADASIL with interhemispheric disconnection features.

PMID- 14586612
TI  - Severe lumbosacral polyradiculopathy complicating epidural anaesthesia.

PMID- 14586613
TI  - Schnitzler's syndrome with neurological findings.

PMID- 14586614
TI  - Effect of antiepileptic drug monotherapy on crystalluria in children and young
      adults.

PMID- 14586615
TI  - Adult-onset dementia with prominent frontal lobe dysfunction in X-linked
      adrenoleukodystrophy with R152C mutation in ABCD1 gene.

PMID- 14586616
TI  - Rupture of a thrombosed intracranial aneurysm during arterial thrombolysis.

PMID- 14586617
TI  - Painful eye movements in aseptic meningitis.

PMID- 14586618
TI  - Role of leukotrienes as indicators of the inflammatory demyelinating reaction in
      x-linked cerebral adrenoleukodystrophy.

PMID- 14586622
TI  - Communications of the European Neurological Society.

PMID- 14586619
TI  - The Vogts: Cecile (1875-1962) and Oskar (1870-1959).

PMID- 14586623
TI  - Expression of fibronectin and tenascin as a demonstration of vital reaction in
      rat skin and muscle.
AB  - The efficiency of immunohistochemical techniques for the diagnosis of vitality of
      wounds decreases for lesions occurring fairly close to death. We analyzed the
      expression of fibronectin (FN) and tenascin (TN) in wounds inflicted in abdominal
      skin of 12 adult rats. An incised injury was made at 5, 10 or 15 min before death
      and another at 5 min after sacrifice, and collected after 45 min. Formalin-fixed
      paraffin-embedded sections from a total of 36 samples (mean 1.5 per wound) were
      immunostained following the streptABC technique. Microscopic examination revealed
      a reticular pattern staining in 18 out of 20 vital samples for FN, 16 out of 20
      for TN, 2 out of 16 postmortem samples for FN and 3 out of 16 for TN.
      Intracellular staining of muscle fibres was observed in 7 out of 20 vital and 5
      out of 16 postmortem samples. FN and TN were detected in most of the vital
      injuries but they are not completely specific. Postmortem staining occurred in a
      few cases probably related to a passive extravasation of these molecules from
      damaged blood vessels. Reactivity of muscle fibres occurs both in vital and
      postmortem lesions, and is not useful in the diagnosis of vitality.

PMID- 14586624
TI  - An unusual complication of stapes surgery: profuse bleeding from the anteriorly
      located sigmoid sinus.
AB  - Major bleeding during stapes surgery is a rare condition. The anterior course of
      the sigmoid sinus is comparatively common in contracted mastoid bones, but rare
      in good pneumatized temporal bones. We report a case of an unusual anterior
      course of the vertical segment of the sigmoid sinus, which led to profuse
      bleeding during a stapedotomy operation. The 34-year-old female patient presented
      with conductive-type hearing loss in the right ear. During the operation, the
      unintentional sliding movement of a blunt curette caused injury to the anteriorly
      positioned sigmoid sinus, which was separated from the posterior wall of the
      external auditory canal by an extremely thin shell of bone. Profuse bleeding from
      the sigmoid sinus was controlled by pushing the middle part of the oxidised
      regenerated cellulose inside the lumen, without compromising the sinus flow.
      After bleeding was restrained, the stapedotomy operation was completed
      successfully. During the 1-year follow-up, there was neither an air-bone gap nor
      a sensorineural hearing loss in pure tone audiogram.

PMID- 14586625
TI  - Should hyperbaric oxygen be added to treatment in idiopathic sudden sensorineural
      hearing loss?
AB  - At present, there is still no agreement about the therapy of idiopathic sudden
      sensorineural hearing loss (ISSHL). Hyperbaric oxygen (HBO) is used in the
      therapy of ISSHL to increase the partial oxygen pressure and the oxygen
      concentration in the inner ear and also to improve the blood profile and the
      microcirculation. In our prospective randomized study, we aimed to investigate
      the therapeutic effects of HBO therapy in the 1st 2 weeks of the onset of ISSHL.
      Fifty-one hospitalized patients with confirmed ISSHL who had received therapy
      were grouped randomly into two groups. Twenty-one patients (group I) received
      steroids, plasma expander dextrans (rheomacrodex), diazepam, pentoxiphylline and
      salt restriction, and 30 patients (group II) received the same basic treatment
      with the addition of HBO therapy. Audiological assessments of the patients were
      performed before and after the treatment. The hearing gains at frequencies of
      250, 500, 1,000, 2,000 and 4,000 Hz were calculated separately. The level of
      hearing loss at the five frequencies was assessed in three groups at the first
      visit: equal or below 60 dB, between 61-80 dB and equal or above 81 dB. The
      average of the mean hearing gains at the five frequencies of the patients
      according to the age groups in group II was compared. The mean hearing gains at
      the five frequencies were compared between the two groups, and statistically
      significant improvement was detected in all the frequencies except at 2,000 Hz in
      group II. The mean hearing gains in group II were found to be significantly high
      in patients with initial hearing levels up to 60 dB in comparison to patients
      with initial hearing levels below 60 dB. When age groups and mean hearing gains
      were compared, there was no statistically significant difference in group I. In
      group II, the mean hearing gains were 39.1+/-18.3 dB in patients younger than 50
      years and 22.7+/-11.3 dB in patients older than 50 years ( P=0.044). In
      conclusion, the addition of HBO therapy to conventional treatment modalities
      significantly improves the outcome of ISSHL, especially at the frequencies of
      250, 500, 1,000 and 4,000 Hz and in hearing loss of above 61 dB. Furthermore, HBO
      therapy was found to be more effective in patients younger than 50 years.

PMID- 14586626
TI  - Neoplasms of the parotid gland in northern Poland, 1991-2000: an epidemiologic
      study.
AB  - A review of patients treated for malignant and benign parotid tumors in a 10-year
      period (1991-2000) in the Pomeranian County of Poland revealed 417 new cases. The
      age-standardized incidence rate was 0.23 and 1.35 per 100,000 inhabitants for
      malignant and benign tumors, respectively. The following data were collected:
      age, sex, place of living, education, job, smoking, symptoms, duration of
      symptoms at the time of diagnosis, result of histopathological tumor examination,
      tumor size, TNM staging and distant metastases. The results were divided into two
      parts: malignant neoplasms and benign neoplasms. The most common malignant
      neoplasms were carcinomas (96.8%), and among them the most numerous were
      mucoepidermoid carcinoma (22.2%), carcinoma in pleomorphic adenoma (20.6%) and
      adenoid cystic carcinoma (15.9%). The most common benign neoplasms were adenomas
      (95.5%), most frequently pleomorphic adenoma (65.5%) and adenolymphoma (24.0%),
      but rarely basal cell adenoma (4.2%). We also observed a steady increase in the
      number of benign parotid tumors in the examined period of time.

PMID- 14586627
TI  - The angiogenic peptide pleiotrophin (PTN/HB-GAM) is expressed in fracture
      healing: an immunohistochemical study in rats.
AB  - INTRODUCTION: Formation of new blood vessels is essential for the process of
      fracture healing. MATERIALS AND METHODS: We investigated the expression of the
      angiogenic factor pleiotrophin/HB-GAM in a closed fracture model in rats by
      immunohistochemical methods. RESULTS: Histologically, 5 days after fracture the
      callus was predominantly composed of fibrous tissue. On day 10 a prominent
      chondral callus connected both ends of the fractured tibia. There was a
      continuous transition from the chondral callus to the newly formed bone adjacent
      to the corticalis of the tibia. On day 15 the amount of woven bone had increased,
      and in 3 of 5 animals the proximal and distal tibiae were connected by a bridge
      of woven bone. Pleiotrophin could be immunostained in fibroblasts and endothelial
      cells of the fibrous tissue between the fractured tibia ends. The chondral callus
      remained largely pleiotrophin-negative. Only single chondrocytes adjacent to the
      newly formed bone were pleiotrophin-positive. On days 10 and 15 strong
      immunoreactivity for pleiotrophin in the well vascularized, newly formed, woven
      bone was detectable. Osteoblasts, endothelial cells and fibroblasts were strongly
      pleiotrophin-positive. CONCLUSIONS: These results show the presence of the
      angiogenic peptide pleiotrophin during fracture healing.

PMID- 14586628
TI  - High migration rate of two types of threaded acetabular cups.
AB  - INTRODUCTION: Survivorship analysis was performed on 479 Link V-type threaded
      cups and on 110 modified V-type Bad Bramstedt cups (a modification of the Link V
      type cup since 1993 with a smaller primary coil) to evaluate the effect of the
      modifications. MATERIALS AND METHODS: Indication for hip arthroplasty with a Link
      V-type cup was an inflammatory arthritis in 310 patients, osteoarthritis in 138
      patients and dysplastic hip joints in 31 patients. The average follow-up was
      8.6+/-3.2 (range 3.0-15.2) years. The 110 modified V-type Bad Bramstedt cups had
      a mean follow-up period of 4.5+/-0.7 (range 3.0-5.9) years, including 49 with
      inflammatory arthritis, 49 with osteoarthritis and 12 with dysplastic hip joints.
      To evaluate the migration rate and radiolucent lines, radiographical examination
      according to the method of Nunn et al. and Delee and Charnley was performed on
      264 Link V-type cups with a mean follow-up period of 8.2+/-2.7 years and 59
      modified V-type Bad Bramstedt cups with a mean follow-up period of 4.6+/-0.7
      years. Relevant parameters influencing cup migration were analysed. RESULTS: The
      cumulative survival rate of the former Link V-type acetabular cup was 94.5% after
      5 years, 88.1% after 10 years and 70.2% after 15 years. The Bad Bramstedt cup
      showed a 5-year survivorship rate of 97.9%. Migration of more than 3 mm or
      tilting of the cup greater than 5 degrees was found in 73% of the former type and
      in 39% of the modified cup. Radiolucent lines greater than 2 mm and detectable in
      two zones appeared in 6.4% of the former Link V-type and in 1.7% of the Bad
      Bramstedt cup design. Among the influencing factors analysed, length of follow-up
      and primary cup positioning showed a significant correlation to cup migration.
      CONCLUSION: The modification of the Link V-type cup showed no satisfactory
      improvement in cup migration. Therefore, both threaded cups were abandoned in
      favour of cementless press-fit cups.

PMID- 14586629
TI  - Expression of BRI, the normal precursor of the amyloid protein of familial
      British dementia, in human brain.
AB  - Familial British dementia (FBD) is characterized neuropathologically by
      deposition of a unique amyloid-forming protein, ABri. It is a fragment of an
      abnormal form of a precursor protein, BRI. In FBD, BRI is elongated by 11 amino
      acids due to a point mutation that prevents recognition of the normal stop codon.
      We have investigated the expression of normal BRI in non-FBD cases. Three
      antibodies were raised against sequences of BRI and were used for immunoblotting
      and immunohistochemistry. Each of these antibodies detected a band at
      approximately 35 kDa by Western blotting. In postmortem human brain tissues, BRI
      was detected as fine granules in the neuronal cytoplasm. Pyramidal neurons in CA3
      and CA4 of the hippocampus as well as Purkinje cells in the cerebellar cortex
      were most intensely stained for BRI. Such a distribution of neurons strongly
      expressing BRI parallels the reported occurrence of ABri deposits in patients
      with FBD. In pathological cases, BRI was detected in dystrophic neurites in
      senile plaques, around lesions in ischemic cases, in torpedo and glumose changes
      in the cerebellum, Lewy neurites, ballooned neurons, and neurons generally in
      hypoxic cases. These results suggest that BRI is transported in neuronal
      processes and is possibly involved in some role in nerve terminals. While a
      physiological role of BRI in brain remains to be determined, the behavior of BRI
      in diverse brain lesions appears to be somewhat analogous to that of amyloid
      precursor protein, which is the source of the beta-amyloid protein of Alzheimer's
      disease.

PMID- 14586630
TI  - Questions on life satisfaction (FLZM) in inflammatory bowel disease.
AB  - BACKGROUND AND AIMS: When assessing quality of care the outcome in terms of
      quality of life (QOL) is of major significance. This study examined QOL in IBD
      outpatients and the contribution of individual expectations and various other
      factors including disease activity. PATIENTS AND METHODS: The study included 306
      outpatients with Crohn's disease and 109 with ulcerative colitis (UC). General
      and health-related QOL was quantified using the instrument Questions on Life
      Satisfaction(Modules). Disease activity was assessed by a questionnaire. Data
      were compared with a normal population sample. RESULTS: Life satisfaction scores
      on general items and on health-related items were significantly lower than in a
      control sample (60.5+/-37.3 and 74.4+/-41.5, respectively) among both CD patients
      (54.3+/-33.2, 59.1+/-38.8) and UC patients (45.4+/-34.0, 52.1+/-40.7). Scores
      were significantly related to severity of disease activity. IBD patients
      attributed particular importance to health-related issues. CONCLUSION: Both
      health-related and general life satisfaction is compromised in IBD outpatients,
      and health-related topics have major impact. Not surprisingly, inflammatory
      activity compromises QOL, which underlines the importance of anti-inflammatory
      strategies. The importance attributed to health-related features is higher in IBD
      patients than in the normal population.

PMID- 14586631
TI  - Surgical results and functional outcome after total anorectal reconstruction by
      double graciloplasty supported by external-source electrostimulation and/or
      implantable pulse generators: an 8-year experience.
AB  - BACKGROUND AND AIMS: Surgical and functional results after abdominoperineal
      resection and total anorectal reconstruction by electrostimulated gracilis muscle
      transposition are still poorly documented. This study prospectively evaluated
      surgical and functional outcome over time in our patients. PATIENTS AND METHODS:
      Twenty-three patients underwent abdominoperineal resection, coloperineal
      pullthrough, double graciloplasty, and loop abdominal stoma. Temporary external
      source intermittent electrostimulation, biofeedback training, and selective
      delayed stimulator implantation to improve unsatisfactory results were carried
      out in the first 13 patients (1st series); thereafter (2nd series) the stimulator
      was implanted during graciloplasty. Surgical and oncological results were
      followed up in all patients. Functional results were evaluated in 16 patients who
      underwent abdominal stoma takedown, eight in each of the two series, by
      anomanometry (up to 1 year) and our own 0-20 scoring system (up to 8 years from
      initial surgery). RESULTS: The rate of major and minor postoperative
      complications was 21.7% and 65%, respectively. Continuous electrostimulation
      proved effective on resting anal pressure. Early clinical assessments showed
      satisfactory functional results (considered as having a score < or =8) in all
      first-group patients, including five who had stimulator support, and in one-half
      of second-group patients. After impairment (at least 2 points) at 1 year in five
      patients, four of whom were from the first group, all functional results improved
      and became satisfactory from 5 years on (1st series) and from 4 years on (2nd
      series). CONCLUSION: Despite marked morbidity the high rate of good results,
      which improved over time, suggests that total anorectal reconstruction is worth
      being performed as part of abdominoperineal resection in well-selected patients
      with a strong motivation to avoid a permanent colostomy.

PMID- 14586632
TI  - Pyloromyotomy through circumbilical incision with fascial extension.
AB  - Extending the fascial incision underlying the circumbilical approach to the shape
      of an 'inverted T' permits easy delivery of the pyloric tumour for Ramstedt's
      pyloromyotomy. This modification was used in 51 consecutive infants (42 male, 9
      female) with a mean age of 4.7 weeks. Extension of the skin incision or
      conversion to the right hypochondrium approach was not necessary in any patient
      and the mean operating time was 31.4 min. Mild wound infection occurred in two
      infants (3.9%) that resolved with antibiotic treatment. Follow-up at 3 months did
      not detect any incisional hernia. This modification allows delivery of small or
      large pyloric tumours, is associated with a low rate of wound infection and does
      not alter the excellent cosmetic finish.

PMID- 14586633
TI  - A case of primary Ewing's sarcoma of the occipital bone presenting with
      obstructive hydrocephalus.
AB  - BACKGROUND: Ewing's sarcomas account for approximately 10% of primary malignant
      bone tumors. While most of the primary Ewing's sarcomas occur in the long bones,
      pelvis, or ribs, approximately 1-6% of these sarcomas arise in the skull. We
      found approximately 50 cases of Ewing's sarcoma of the calvarium reported in our
      search of the literature. Of these, 36 cases were reported in detail. CASE REPORT
      AND DISCUSSION: In this article we describe a rare case of primary Ewing's
      sarcoma of the occipital bone presenting with acute obstructive hydrocephalus and
      review the literature.

PMID- 14586634
TI  - Acquired Chiari type I malformation managed by supratentorial cranial
      enlargement.
AB  - INTRODUCTION: Acquired Chiari type-I malformation in hydrocephalic patients who
      have undergone surgical treatment was initially thought to depend on a
      craniocephalic disproportion induced by the cerebrospinal (CSF) shunt. However,
      most of the reports in the literature deal with children with lumbo-peritoneal
      shunts and emphasize the pathogenic role of the cranio-spinal pressure
      differential across the foramen magnum brought about by this type of shunt.
      METHOD: In the present report, the authors describe two further cases of
      symptomatic acquired Chiari type-I malformation observed in two adolescents
      operated on for correction of pseudotumor cerebri in one (lumbo-peritoneal shunt)
      and of a suprasellar arachnoid cyst (cysto-ventriculo-peritoneal shunt) in the
      other. RESULTS: In both subjects, both the clinical manifestations and the
      cerebellar tonsillar herniation regressed after supratentorial cranial expansion,
      without the need for any manipulation of the shunt devices implanted earlier.
      DISCUSSION: These results, together with the observation of the concomitant
      upward and downward herniation of the cerebellum in both patients, indicate that
      secondary craniocephalic disproportion plays a relevant role in the genesis of
      acquired Chiari type-I malformation in children bearing extrathecal CSF shunts.

PMID- 14586635
TI  - The effect of chronic cortisol elevation on urea metabolism and excretion in the
      rainbow trout (Oncorhynchus mykiss).
AB  - The objective of this study was to investigate the possible involvement of
      cortisol in controlling urea metabolism and excretion in the ammoniotelic rainbow
      trout (Oncorhynchus mykiss). Trout fitted with dorsal aortic and internal urinary
      catheters received either no implant (control), or were implanted with coconut
      oil (sham), cortisol in coconut oil, RU486, a glucocorticoid receptor blocker, in
      coconut oil, or cortisol+RU486 in coconut oil, and monitored over 72 h. Rainbow
      trout treated with cortisol (+/- RU486) had similarly elevated plasma cortisol
      concentrations that were six fold greater than in control and sham fish. Elevated
      circulating cortisol concentrations caused a three-fold rise in plasma and urine
      urea concentrations, which was blocked by RU486. Similarly, a positive
      correlation between plasma cortisol and plasma urea concentrations was observed
      in fish treated with cortisol alone but not in fish treated with cortisol+RU486.
      Cortisol treatment caused an elevation in branchial (two fold higher) and urinary
      (three fold higher) excretion rates of urea compared to sham-implanted fish,
      which was prevented by treatment with RU486. However, as branchial and renal
      clearance were unaffected, there appears to be no stimulation or inhibition of
      urea excretion mechanisms in the gill or kidney separate from effects due to
      changes in plasma urea concentrations. Thus, cortisol and glucocorticoid
      receptors appear to be involved in the regulation of endogenous urea production
      but not in the control of urea excretory mechanisms in the ammoniotelic trout.

PMID- 14586636
TI  - Prostaglandin E2 induces upregulation of Na+ transport across Xenopus lung
      epithelium.
AB  - The apical mucus on pulmonary epithelia is not only critical for physiological
      functions such as gas exchange or inflammatory processes, but also contains
      surfactants and multiple molecules that mediate cellular responses. A tight
      control of transepithelial ion transport maintains viscosity of this layer and,
      e.g., the amiloride-sensitive sodium channels (ENaCs) in lung epithelia of
      vertebrates are the most important regulatory sites for transcellular sodium
      uptake. Dysfunction of this sodium transport results in reduced liquid absorption
      and causes massive problems with gas exchange. We used dissected lungs of Xenopus
      laevis in Ussing chambers to investigate the influence of prostaglandin E2 (PGE2)
      on the regulation of short-circuit current (ISC) and amiloride-sensitive sodium
      absorption (Iami). Apical application of PGE2 (1 microM) increased ISC by 38% and
      Iami by approximately 60%. In contrast, a different prostaglandin, PGI2, neither
      affected ISC nor Iami. Forskolin increased current to a similar magnitude and
      preincubation of the lung with an RP-isomer of cyclic AMP, an inhibitor of
      protein kinase A (PKA), abolished the effects of both PGE2 and forskolin.
      Transepithelial Na+ uptake was also upregulated by the prostaglandin receptor
      agonists misoprostol and sulprostone. The Iami in Xenopus oocytes that
      heterologously expressed ENaCs was not affected by PGE2.

PMID- 14586637
TI  - Metabolic responses to glucoprivation induced by 2-deoxy-D-glucose in Brycon
      cephalus (Teleostei, Characidae).
AB  - The effects of functional cytoglucopenia provoked by 2-deoxy-D-glucose (2-DG)
      were studied in adult Brycon cephalus, an omnivorous fish from the Amazon Basin
      in Brazil. Glycogen content in liver and muscle as well as plasmatic glucose,
      free fatty acids (FFA), insulin, and glucagon were measured. After 48 h fasting,
      an intraperitoneal saline injection (NaCl 0.6 g/100 ml) was administered to
      control fish, whereas the experimental group received 2-DG, dissolved in saline,
      in the dosage of 80 mg/kg (0.487 mmol/kg) or 150 mg/kg (0.914 mmol/kg) body
      weight; injection volume was 5 ml in all treatments. Blood and tissue samples
      were taken immediately before, and 2, 8, 10, and 24 h after administration of the
      drug or saline. Fish injected with both doses of 2-DG showed a marked increase in
      glycemia levels. Liver and muscle glycogen decreased after 2-DG administration
      and reached their lowest values 10-24 h after injection, while in control animals
      no significant changes were observed. Elevation in plasma glucagon was observed
      only in response to the maximum dosage of 2-DG administered, especially 10 h and
      24 h post-injection. Plasma insulin levels were lower in animals treated with the
      glucose analogue but only statistically significant 24 h after drug
      administration. In conclusion, the administration of the non-metabolizable
      glucose analogue 2-DG in B. cephalus is a stimulus to generate responses towards
      an increase in the glucose available to tissues, which is a characteristic of a
      fasting situation. All the above data support the interest of 2-DG administration
      as a model to study carbohydrate metabolism adjustment mechanisms in fish.

PMID- 14586638
TI  - A genome-wide search for allergic response (atopy) genes in three ethnic groups:
      Collaborative Study on the Genetics of Asthma.
AB  - Atopy is an IgE-mediated condition known to aggregate in families and is a major
      risk factor for asthma. As part of the Collaborative Study on the Genetics of
      Asthma (CSGA), a genome-wide scan for atopy, defined by skin sensitivity to one
      or more common environmental allergens, was conducted in 287 CSGA families (115
      African American, 138 Caucasian and 34 Hispanic). Using a nonparametric genetic
      analysis approach, two regions were observed in the sample of all families that
      yielded multipoint lod scores >1.5 (chromosome 11q, lod=1.55 between D11S1986 and
      D11S1998; chromosome 20p between D20S473 and D20S604, lod=1.54). Modeling that
      included multiple genomic positions simultaneously indicated that four
      chromosomal regions accounted for the majority of evidence for linkage in the
      combined families. These four regions are on chromosomes 10p near D10S1412
      (lod=0.94), 11q near D11S1986 (lod=1.76), 17q near D17S784 (lod=0.97) and 20p
      near D20S473 (lod=1.74). In the subset of pedigrees giving positive evidence for
      linkage on chromosome 11q, the evidence for linkage increased by lod scores
      greater than one in four other chromosomal regions: 5q (D5S1480, lod=1.65), 8p
      (D8S1113, lod=1.60), 12p (D12S372, lod=1.54) and 14q (D14S749, lod=1.70). These
      results suggest that several regions may harbor genes contributing to the risk
      for atopy and these may interact with one another in a complex manner.

PMID- 14586639
TI  - Excavating Y-chromosome haplotype strata in Anatolia.
AB  - Analysis of 89 biallelic polymorphisms in 523 Turkish Y chromosomes revealed 52
      distinct haplotypes with considerable haplogroup substructure, as exemplified by
      their respective levels of accumulated diversity at ten short tandem repeat (STR)
      loci. The major components (haplogroups E3b, G, J, I, L, N, K2, and R1; 94.1%)
      are shared with European and neighboring Near Eastern populations and contrast
      with only a minor share of haplogroups related to Central Asian (C, Q and O;
      3.4%), Indian (H, R2; 1.5%) and African (A, E3*, E3a; 1%) affinity. The expansion
      times for 20 haplogroup assemblages was estimated from associated STR diversity.
      This comprehensive characterization of Y-chromosome heritage addresses many
      multifaceted aspects of Anatolian prehistory, including: (1) the most frequent
      haplogroup, J, splits into two sub-clades, one of which (J2) shows decreasing
      variances with increasing latitude, compatible with a northward expansion; (2)
      haplogroups G1 and L show affinities with south Caucasus populations in their
      geographic distribution as well as STR motifs; (3) frequency of haplogroup I,
      which originated in Europe, declines with increasing longitude, indicating gene
      flow arriving from Europe; (4) conversely, haplogroup G2 radiates towards Europe;
      (5) haplogroup E3b3 displays a latitudinal correlation with decreasing frequency
      northward; (6) haplogroup R1b3 emanates from Turkey towards Southeast Europe and
      Caucasia and; (7) high resolution SNP analysis provides evidence of a detectable
      yet weak signal (<9%) of recent paternal gene flow from Central Asia. The variety
      of Turkish haplotypes is witness to Turkey being both an important source and
      recipient of gene flow.

PMID- 14586640
TI  - The thymidylate synthase tandem repeat polymorphism is not associated with
      homocysteine concentrations in healthy young subjects.
AB  - Thymidylate synthase (TYMS) and 5,10-methylenetetrahydrofolate reductase (MTHFR)
      may compete for their common cofactor 5,10-methylenetetrahyhdrofolate (5,10
      meTHF). Limiting 5,10-meTHF results in elevated homocysteine, especially in
      individuals homozygous for the T allele of the MTHFR C677T polymorphism. The TYMS
      gene has a tandem repeat polymorphism (two repeats or three repeats, designated
      2R or 3R, respectively), which may also affect homocysteine concentrations. The
      3R allele is subject to increased translational efficiency in vitro and the 3R3R
      genotype is associated with both decreased serum folate and elevated plasma
      homocysteine (tHcy) in a population of Singapore Chinese. We assessed the
      relationship between TYMS genotype and key biochemical and genetic variables in a
      random sample of 392 healthy young Northwestern European men and women. The tHcy
      concentrations for 3R3R homozygotes (median 8.5 micromol/l) did not differ
      significantly from those for 2R2R homozygotes (median 8.7 micromol/l) or 2R3R
      heterozygotes (median 9.3 micromol/l) in the population as a whole (P=0.43), or
      in subsets of subjects with low serum folate (P=0.60) or the MTHFR 677TT genotype
      (P=0.90). Furthermore, there was no trend toward elevated tHcy in 3R3R
      homozygotes. Similarly, the TYMS tandem repeat polymorphism was not associated
      with serum folate concentrations. Our findings indicate that the TYMS 3R3R
      genotype is not a determinant of homocysteine in this sample of healthy young
      Caucasian adults from Northern Ireland.

PMID- 14586641
TI  - Isolation, genetic variation and expression of TIR-NBS-LRR resistance gene
      analogs from western white pine ( Pinus monticola Dougl. ex. D. Don.).
AB  - Western white pine ( Pinus monticola Dougl. ex. D. Don., WWP) shows genetic
      variation in disease resistance to white pine blister rust ( Cronartium
      ribicola). Most plant disease resistance (R) genes encode proteins that belong to
      a superfamily with nucleotide-binding site domains (NBS) and C-terminal leucine
      rich repeats (LRR). In this work a PCR strategy was used to clone R gene analogs
      (RGAs) from WWP using oligonucleotide primers based on the conserved sequence
      motifs in the NBS domain of angiosperm NBS-LRR genes. Sixty-seven NBS sequences
      were cloned from disease-resistant trees. BLAST searches in GenBank revealed that
      they shared significant identity to well-characterized R genes from angiosperms,
      including L and M genes from flax, the tobacco N gene and the soybean gene LM6.
      Sequence alignments revealed that the RGAs from WWP contained the conserved
      motifs identified in angiosperm NBS domains, especially those motifs specific for
      TIR-NBS-LRR proteins. Phylogenic analysis of plant R genes and RGAs indicated
      that all cloned WWP RGAs can be grouped into one major branch together with well
      known R proteins carrying a TIR domain, suggesting they belong to the subfamily
      of TIR-NBS-LRR genes. In one phylogenic tree, WWP RGAs were further subdivided
      into fourteen clusters with an amino acid sequence identity threshold of 75%.
      cDNA cloning and RT-PCR analysis with gene-specific primers demonstrated that
      members of 10 of the 14 RGA classes were expressed in foliage tissues, suggesting
      that a large and diverse NBS-LRR gene family may be functional in conifers. These
      results provide evidence for the hypothesis that conifer RGAs share a common
      origin with R genes from angiosperms, and some of them may play important roles
      in defense mechanisms that confer disease resistance in western white pine.
      Ratios of non-synonymous to synonymous nucleotide substitutions (Ka/Ks) in the
      WWP NBS domains were greater than 1 or close to 1, indicating that diversifying
      selection and/or neutral selection operate on the NBS domains of the WWP RGA
      family.

PMID- 14586642
TI  - Changing patterns in intestinal parasitic infections among Southeast Asian
      laborers in Taiwan.
AB  - In order to determine whether there are changing patterns in intestinal parasitic
      infections among foreign laborers in North Taiwan, one fecal specimen was
      obtained from each of 1,569 laborers and examined by the formalin-ethyl acetate
      sedimentation technique. The prevalence of intestinal parasitic infections was
      8.2%. Females (11.7%) had a significantly higher prevalence than males (6.9%),
      although there was no significant difference between Filipinos (7.7%), Thais
      (8.3%) and Indonesians (12.5%). Blastocystis hominis (3.4%) had the highest
      prevalence among the nine species of parasites detected. The significantly higher
      prevalence of B. hominis in the entry examination indicates an increasing trend
      in incoming Southeast Asian laborers. In addition, the prevalence of soil
      transmitted helminth infections has become extremely low. Female laborers had a
      significantly higher positive rate. Although Opisthorchis viverrini/Clonorchis
      sinensis remains prevalent among Thais, the positive rate was also significantly
      reduced. These epidemiological patterns are different from those observed in
      previous studies and may be attributed to the long-term and constant movement of
      the foreign laborers.

PMID- 14586643
TI  - Fasciola hepatica: the effect of food quality on the development of redial
      generations in Galba truncatula infected with allopatric miracidia.
AB  - Individual bimiracidial infections of French Galba truncatula with an allopatric
      (Moroccan) isolate of Fasciola hepatica were carried out under laboratory
      conditions to count free rediae and intraredial daughter rediae in snails just
      after their death, and to determine whether feeding the snails on lettuce only or
      lettuce plus Tetraphyll had an effect on the development of redial generations.
      Controls consisted of snails infected with sympatric (French) miracidia and
      reared with lettuce only. In the allopatric group, reared with lettuce only as
      food, a higher mortality rate of snails in the first 4 weeks of the experiment
      was noted, and most G. truncatula showed 1-sporocyst infections, with the usual
      development of redial generations. Compared to the sympatric group, the growth of
      the first mother redia (R1a redia) in each snail of the allopatric group was
      significantly slower during the first weeks of infection, whereas a significantly
      increased formation of intraredial daughter rediae in the other mother rediae
      (R1b rediae) was noted over the same period. In the allopatric group, reared with
      cos lettuce and commercial fish food, 1-sporocyst infections (45.5% of snails)
      and 2-sporocyst infections (53.9%), with the usual development of redial
      generations, were noted. Compared to the sympatric group, a significantly slower
      development of the first mother redia during the first weeks of the experiment
      was noted in the 1-sporocyst infections, whereas the values in the 2-sporocyst
      infections did not significantly differ from those noted in the sympatric group.
      Similar results were noted for the production of intraredial daughter rediae in
      the R1b rediae during the first weeks of the experiment. In all infections
      derived from the growth of a single sporocyst per snail, the differentiation of
      numerous daughter rediae inside R1b rediae would be induced by the slow growth of
      the R1a redia (from which the most important group of R2a rediae originated)
      during the first weeks of infection and might represent a mechanism to replace
      free rediae absent from the inside of the snail.

PMID- 14586644
TI  - Simulation of tumor-induced angiogenesis and its response to anti-angiogenic drug
      treatment: mode of drug delivery and clearance rate dependencies.
AB  - Tumor cells secrete diffusible substances collectively called tumor angiogenic
      factors (TAFs), most notably vascular endothelial growth factor (VEGF) and basic
      fibroblast growth factor (bFGF), which in turn stimulate endothelial cell
      migration and thus angiogenesis, or new blood vessel formation. Anti-angiogenic
      drugs for cancer treatment are receiving much attention, with endostatin
      identified as one of the potent inhibitors. Although the mechanisms of action of
      endostatin are yet to be fully elucidated, there is evidence that bFGF and
      endostatin may bind competitively to heparan sulfate proteoglycan receptors on
      endothelial cells, or endostatin may otherwise downregulate bFGF or VEGF and its
      receptors, putatively inhibiting cell proliferation. To test these and other
      hypotheses of inhibitory action that can be similarly formulated, for other TAF
      inhibitors as well as endostatin, we have developed a mathematical model of
      extratumoral angiogenesis in cancer in response to specific anti-angiogenic drug
      treatment. It is built on previous work, a modification and augmentation of
      published models, and is expressed as four nonlinear partial differential
      equations, with specific terms for endothelial cell proliferation, degradation,
      and endostatin-TAF inhibition, and a stochastic, discretized version of this
      model to represent vessel growth. Our extended model reproduces the simulated
      kinetics of angiogenesis in a mouse tumor model reported earlier. We assessed the
      anti-angiogenic kinetic behavior of our extended model by simulating dynamic
      responses to exogenous endostatin treatment in the same mouse model, using four
      dosage regimens, two of these reported for in vivo pre-clinical or clinical
      studies, and two 10 times greater: daily single bolus injections of 20 mg/kg per
      day and 200 mg/kg per day, and constant infusions of 20 mg/kg per day and 200
      mg/kg per day, each for 20 simulated days. We also explored the effects of drug
      clearance, over an eightfold range of clearance rates that include scaled
      clearances for endostatin, a sister-drug angiostatin, or similar drugs with
      clearances in this range. Predictively, our simulation results suggest
      ineffectiveness of the bolus injection protocols, consistent with in vivo data
      with angiostatin treatment, whereas simulated constant infusion of endostatin in
      the mouse model effectively suppresses angiogenesis after only 3 days of
      treatment, at the lowest dose, over a wide range of drug clearance rates.

PMID- 14586645
TI  - Differential alterations of the genes in the CDKN2A-CCND1-CDK4-RB1 pathway are
      associated with the development of head and neck squamous cell carcinoma in
      Indian patients.
AB  - PURPOSE: The aim of this study was to analyse the alterations of the genes in the
      CDKN2A/CCND1/CDK4/RB1 pathway in the G1-S phase of the cell cycle during
      development of head and neck squamous cell carcinoma (HNSCC). METHODS: The
      alterations of these genes were analysed in 22 dysplastic lesions, 26 stage-I/II
      and 33 stage-III/IV HNSCC tumours of Indian patients. RESULTS: The alterations
      [mutation, hypermethylation, homozygous deletion and loss of
      heterozygosity/microsatellite size alteration (LOH/MA)] in the CDKN2A were found
      to be highest in 57% of the samples, followed by CCND1 amplification and LOH/MA
      at the RB1 locus in 14% and 8.5% of the samples, respectively. No dominant CDK4
      Arg24Cys mutation was seen in our samples. Comparatively high frequency of CDKN2A
      alterations (except homozygous deletion) was found in dysplastic head and neck
      lesions and remained almost constant or increased during progression of the
      tumour, whereas the homozygous deletion of CDKN2A and the alterations in CCND1
      and RB1 genes were seen mainly in the later stages of the tumour. CONCLUSIONS:
      Our study suggested that mutation/hypermethylation/allelic alterations (LOH/MA)
      of CDKN2A were associated with the development of dysplastic head and neck
      lesions. All the other alterations might provide some cumulative effect during
      progression of later stages of the tumour to have selective growth advantages.

PMID- 14586646
TI  - Congenital diaphragmatic eventration and bilateral uretero-hydronephrosis in a
      patient with neonatal Marfan syndrome caused by a mutation in exon 25 of the FBN1
      gene and review of the literature.
AB  - Neonatal Marfan syndrome, the most severe presentation of Marfan syndrome
      phenotypes (MIM 154700), is characterised mainly by joint contractures,
      arachnodactyly, loose skin, crumpled ears, severe atrioventricular valve
      dysfunction and pulmonary emphysema. Death usually occurs within the first 2
      years of life from congestive heart failure. We describe here a newborn male with
      many typical characteristics of neonatal Marfan syndrome associated with a
      diaphragmatic eventration and a bilateral uretero-hydronephrosis with bladder
      dilatation. He died from cardiac failure due to severe tricuspid and mitral
      regurgitation at 62 h of age. CONCLUSION: Molecular analysis showed a
      heterozygous missense mutation at nucleotide 3165 (3165T>G) in exon 25 of the
      FBN1 gene, resulting in the substitution of cysteine for tryptophan (C1055W).

PMID- 14586647
TI  - Criteria for decision-making--what makes sense?
AB  - Rational medical decision-making increasingly demands the acquisition of critical
      appraisal skills through application of the principles of evidence-based medicine
      and clinical epidemiology. Moreover, mastery of information technology to reduce
      time constraints and data overload is necessary. Ultimately, decision-making has
      to take into account patient preferences in order to establish real communication
      to optimise shared decision endeavours.

PMID- 14586648
TI  - The impact of screening for propionic and methylmalonic acidaemia.
AB  - The outcome of the severe variants of propionic and methylmalonic acidaemia is
      not good. Patients with these disorders have increased concentrations of
      propionylcarnitine and using tandem mass spectrometry to detect this compound, it
      is possible to screen in the newborn period. Various criteria have been used to
      identify the patients but only a small number of patients have been diagnosed so
      far and some have been missed. Furthermore many will have already presented
      before the result of the screening test is available. CONCLUSION: It is not yet
      clear whether the outcome is better for those identified in screening programmes.

PMID- 14586649
TI  - Severe transient hyperinsulinaemic hypoglycaemia: two neonates without
      predisposing factors and a review of the literature.
AB  - We report on transient hyperinsulinism (HI), presenting as severe congenital HI,
      in two neonates born without intrauterine growth restriction, maternal diabetes,
      perinatal asphyxia or Rhesus/platelet isoimmunisation. The neonates developed
      early (<6 h of life), symptomatic, non-ketotic hypoglycaemia (0-0.66 mmol/l),
      associated with elevated insulin levels (40-200 mU/l), and required high glucose
      infusion rates (22-24 mg/kg per min) to maintain normoglycaemia. However, both
      babies were diazoxide-sensitive and did not require glucose infusions beyond 2
      weeks of life. Neither neonate had elevated serum ammonia levels or evidence of a
      metabolic disorder. CONCLUSION: Transient hyperinsulinism can occur in newborns
      delivered uneventfully without significant perinatal complications. The unusual
      sensitivity to medical treatment in these cases of neonatal-onset
      hyperinsulinaemic hypoglycaemia underscores the importance of careful medical
      management of severe congenital hyperinsulinism. Careful consideration of the
      indication and if necessary, timing and extent of pancreatectomy is required,
      while maintaining euglycaemia to protect the developing brain.

PMID- 14586650
TI  - Multiple brain abscesses in an extremely preterm infant: treatment surveillance
      with interleukin-6 in the CSF.

PMID- 14586651
TI  - Experimental rat model for therapeutic retinal pigment epithelium transplantation
      -unequivocal microscopic identification of human donor cells by in situ
      hybridisation of human-specific Alu sequences.
AB  - Transplantation of retinal pigment epithelial (RPE) cells is discussed as a
      possible therapeutic approach for retinal degeneration. Xenogeneic
      transplantation of human RPE cells in animal models has been studied extensively.
      Various methods have been used to identify the graft cells, but these methods
      interfere with cell behaviour so that the monitored physiological post
      transplantation course may be influenced. In the present study, we applied a
      method for an unequivocal identification of the graft cells without interfering
      cell metabolism or behaviour using in situ hybridisation (ISH) of human specific
      Alu sequences. Visualisation of the strong extended nuclear signal of Alu
      sequences was much easier than that of the small nuclear signals of donor
      specific sex chromosome probes. With Alu probe, even single graft cells can be
      identified and their development can be observed in short-term and long-term
      studies. With this procedure, we could prove that donor cells were injected
      correctly into the subretinal space by a special injection technique that we
      developed previously. In combination with immunohistochemistry, donor cells could
      be clearly discriminated from macrophages, which contained phagocytosed donor
      cell fragments. Application of these ISH methods for species-specific
      identification was valuable for follow-up-studies of RPE transplantation.

PMID- 14586653
TI  - Inhibition of metamorphosis by RFamide neuropeptides in planula larvae of
      Hydractinia echinata.
AB  - The primitive nervous system in planula larvae of Hydractinia echinata (Cnidaria)
      has sensory neurons containing LWamide or RFamide neuropeptides. LWamides have
      been shown to induce metamorphosis of planula larvae into adult polyps. We report
      here that RFamides act antagonistically to LWamides. RFamides inhibit
      metamorphosis when applied to planula larvae during metamorphosis induction by
      treatment with LWamides (or other inducing agents such as CsCl ions,
      diacylglycerol and bacterial inducers). Our results show further that RFamides
      act downstream of LWamide release, presumably directly on target cells mediating
      metamorphosis. These observations support a model in which metamorphosis in H.
      echinata is regulated by sensory neurons secreting LWamides and RFamides in
      response to environmental cues.

PMID- 14586652
TI  - The plasmacytoid monocyte/interferon producing cells.

PMID- 14586655
TI  - New insights into the function of tocopherols in plants.

PMID- 14586654
TI  - Sulfur assimilation in soybean ( Glycine max [L.] Merr.): molecular cloning and
      characterization of a cytosolic isoform of serine acetyltransferase.
AB  - A full-length cDNA clone encoding a cytosolic isoform of serine acetyltransferase
      (SATase; EC 2.3.1.30) was isolated by screening a soybean seedling cDNA library
      with a (32)P-labeled expressed sequence tag. Nucleotide sequence analysis of the
      isolated cDNA revealed a single open-reading frame of 858 base pairs encoding a
      30-kDa polypeptide. The deduced amino acid sequence of soybean SATase revealed
      significant homology with other plant SATases. Analysis of genomic DNA by
      Southern blotting indicated that SATase is encoded by a small gene family. The
      authenticity of the isolated SATase cDNA was confirmed by the expression of the
      cDNA in an Escherichia coli cysteine-auxotrophic mutant resulting in the growth
      of the mutant in minimal medium without cysteine. Expression of soybean SATase in
      E. coli resulted in the production of a 34-kDa protein that was subsequently
      purified by nickel-affinity column chromatography. The purified protein exhibited
      SATase activity, indicating that the E. coli-expressed protein is a functionally
      active SATase. The recombinant soybean SATase was inhibited by l-cysteine, the
      end product of the cysteine biosynthetic pathway. Antibodies raised against the
      recombinant soybean SATase cross-reacted with a 34-kDa protein from Arabidopsis
      leaves, but failed to detect any proteins from soybean leaves and seeds. Reverse
      transcriptase-polymerase chain reaction analysis indicated that SATase mRNA was
      expressed at low levels during soybean seed development. In comparison to
      Arabidopsis leaves, the SATase activity was several-fold lower in soybean leaves
      and seeds, suggesting that SATase is a low-abundance enzyme.

PMID- 14586656
TI  - Cloning of soybean genes induced during hypersensitive cell death caused by
      syringolide elicitor.
AB  - Syringolide elicitors produced by bacteria expressing Pseudomonas syringae pv.
      glycinea avirulence gene D (avrD) induce hypersensitive cell death (HCD) only in
      soybean (Glycine max [L.] Merr.) plants carrying the Rpg4 disease resistance
      gene. Employing a differential display method, we isolated 13 gene fragments
      induced in cultured cells of a soybean cultivar Harosoy (Rpg4) treated with
      syringolides. Several genes for isolated fragments were induced by syringolides
      in an rpg4 cultivar Acme as well as in Harosoy; however, the genes for seven
      fragments designated as SIH (for syringolide-induced/ HCD associated) were
      induced exclusively or strongly in Harosoy. cDNA clones for SIH genes were
      obtained from a cDNA library of Harosoy treated with syringolide. Several
      sequences are homologous to proteins associated with plant defense responses. The
      SIH genes did not respond to a non-specific beta-glucan elicitor, which induces
      phytoalexin accumulation but not HCD, suggesting that the induction of the SIH
      genes is specific for the syringolide-Harosoy interaction. HCD and the induction
      of SIH genes by syringolides were independent of H(2)O(2). On the other hand,
      Ca(2+) was required for HCD and the induction of some SIH genes. These results
      suggest that the induction of SIH genes by syringolides could be activated
      through the syringolide-specific signaling pathway and the SIH gene products may
      play an important role(s) in the processes of HCD induced by syringolides.

PMID- 14586657
TI  - Active and passive behaviour in the regulation of stiffness of the lateral wall
      in outer hair cells of the guinea-pig.
AB  - The stiffness of the outer hair cell (OHC) lateral wall, measured by the
      micropipette aspiration technique, is non-linear, decreasing from the ciliary
      pole (stiffness parameter Sp 1.83+/-0.13 nN/microm n=10) towards the cell base
      (Sp 1.14+/-0.16 nN/microm, n=10) irrespective of the cochleoapical or
      cochleobasal origin of the cells. The length of the aspirated lateral wall
      segment was related exponentially to the duration of the applied negative
      pressure (6 cm H2O) in the synaptic region of the OHCs whereas an active, sigmoid
      component was observed between 30 and 60 s in the supranuclear regions. A
      significant increase of the midlateral wall stiffness (to 1.91+/-0.23 nN/microm;
      n=10) was observed in calcium-free medium and the sigmoid component of the
      response of the lateral wall was abolished. Salicylate (5 mM) had no significant
      effect on the active sigmoid behaviour of the lateral wall (n=10). Gadolinium (5
      mM), a non-specific cation channel blocker, increased the stiffness of the
      lateral wall and attenuated the active component (n=10). The motor protein
      prestin thus does not seem to be involved in the active stiffness regulation seen
      in this study. A role for the cortical cytoskeleton in the regulation of
      stiffness seems reasonable according to our model. The mechanism may involve
      calcium-dependent metabolic modification of cytoskeletal or membrane proteins.

PMID- 14586658
TI  - Mechanism of the positive contractile effect of nitric oxide on rat ventricular
      cardiomyocytes with positive force/frequency relationship.
AB  - The positive contractile effect of nitric oxide (NO) donors was studied on
      isolated rat ventricular cardiomyocytes within a range of a positive
      force/frequency relationship. We determined whether the observed effect depended
      on cGMP. The NO donors S-nitroso-acetyl-D,L-penicillamine (SNAP) and N-[4-[1-(3
      aminopropyl)-2-hydroxy-2-nitrosohydrazino]butyl]-1,3-propanediamine (spermine
      NONO) increased contractile responsiveness transiently in a concentration- and
      frequency-dependent manner. The influence of NO donors on cGMP levels was
      enhanced under beating conditions. The positive contractile effect of NO donors
      was inhibited by adenosine 3',5'-cyclic monophosphothioate Rp diastereomer (Rp
      cAMPS), but not by bisindolylmaleimide. Inhibition of the soluble guanylyl
      cyclase (sGC) by 1 H-[1,2,4]-oxadiazole-[4,3-a]-quinoxalin-1-one (ODQ) inhibited
      the positive contractile effect of NO donors. Direct activation of sGC by 3-(5'
      hydroxymethyl-2'-furyl)-1-benzylindazole (YC1) or addition of 8-bromo cGMP
      increased cell contractility comparably to NO donors. Inhibition of G(alphas)
      proteins by NF441 inhibited the positive contractile effect of NO donors. In
      contrast, NO donors did not potentiate the positive contractile effect of
      forskolin. These results demonstrate that the positive contractile effect of NO
      donors on rat ventricular cardiomyocytes working in a range of a positive
      force/frequency relationships is enhanced. It is mediated by NO-dependent
      stimulation of the sGC interacting with G(alphas) proteins.

PMID- 14586659
TI  - An ER export signal accelerates the surface expression of shal potassium channels
      in pyloric neurons of the lobster stomatogastric ganglion.
AB  - The shal gene encoding the transient potassium current, I(A), plays important
      roles in shaping the firing properties of neurons in the pyloric network in the
      stomatogastric ganglion (STG) of the spiny lobster, Panulirus interruptus.
      However, when we overexpressed the shal protein in pyloric dilator (PD) neurons,
      the effect of increased I(A )was compensated by a parallel upregulation of the
      hyperpolarization activated inward current ( I(h)). In an attempt to temporally
      separate the overexpression of shal from the compensatory up-regulation of I(h)
      channels, we inserted an endoplasmic reticulum (ER) export signal sequence,
      FCYENE, into the shal gene. This signal sequence accelerated the surface
      expression of shal protein in Xenopus oocytes and PD neurons. However, the
      accelerated expression of shal still did not alter the firing properties of the
      injected neuron, suggesting that the compensatory upregulation of I(h) occurs
      simultaneously with the upregulation of I(A).

PMID- 14586660
TI  - Laparoscopic surgical concepts of morbid obesity.
AB  - BACKGROUND: According to the WHO, obesity and obesity with associated morbidity
      constitute a chronic, multi-factorial condition requiring treatment. Conservative
      treatment has been shown in long-term studies to be ineffective in morbid
      obesity. Surgical treatments break down into restrictive, malabsorptive, combined
      restrictive and malabsorptive or motility-reducing procedures. METHOD AND
      RESULTS: Laparoscopic implantation of an adjustable gastric band is an efficient
      restrictive measure for treating the majority of patients with this condition.
      The adjustable gastric band enables weight loss and food intake to be adapted to
      the individual patient's need. Of these patients, 80-90% can expect to lose 55
      70% of their excess weight. Vertical banded gastroplasty is losing ground among
      the restrictive options. Preliminary experiences are encouraging, but the long
      term results are disappointing when assessed by the standard criteria. Gastric
      bypass is gaining ground in Europe and is a standard procedure in the USA. This
      operation is estimated to give a 70-80% loss in excess weight, and provides a
      better quality of life than do restrictive procedures. The biliopancreatic
      diversion with duodenal switch combines a sleeve gastrectomy with a duodeno-ileal
      switch to achieve maximum weight loss. Consistent excess weight loss of between
      70% and 80% is achieved, with acceptable decreased long-term nutritional
      complications. The laparoscopic approach to this procedure has successfully
      created a surgical technique with optimum benefit and minimal morbidity,
      especially in the super-obese patient. Intra-gastric stimulation is the least
      invasive surgical procedure at present. However, the excess weight loss is lowest
      with this method, at only 32% in the first 2 years after the operation.
      CONCLUSION: Provided that safety recommendations are observed, laparoscopic
      operations for obesity have a fairly low risk. The mortality rate in centres with
      experienced staff is less than 0.3%. The death rate due to untreated morbid
      obesity is significantly higher than in a comparable group of patients after
      surgery.

PMID- 14586661
TI  - Endoscopic resection in neoplastic lesions of the oesophagus.
AB  - BACKGROUND: Endoscopic resection has gained more and more importance in the
      treatment of early oesophageal neoplasia over the past few years. The choice of
      the different available techniques depends on the site, the macroscopic type of
      the tumour and the personal experience of the endoscopist. METHODS: The "suck-and
      cut" technique with ligation device or cap should be favoured over normal strip
      biopsy in the oesophagus because of the size of the resected specimen and the
      technical feasibility. RESULTS: Endoscopic resection (ER) of high-grade intra
      epithelial neoplasia and mucosal adenocarcinoma in Barrett's oesophagus should be
      considered as the treatment of choice, due to excellent long-term results. First
      mid-term results of endoscopic therapy of early squamous cell neoplasia in the
      oesophagus show promising results; however, long-term results are awaited.
      CONCLUSION: ER of oesophageal neoplastic lesions is a safe and effective method
      but should be performed only by experienced endoscopists.

PMID- 14586662
TI  - Checking for interviewer bias in outcome assessment: a method for strengthening
      the design of prospective, randomised trials in surgery.
AB  - BACKGROUND: Blind, randomised trials are conceived as the gold standard in
      clinical research, but this ideal, in its strict sense, can rarely be achieved in
      surgical settings. One way to strengthen the study design is to check for
      observer bias in the assessment and evaluation of surgical outcome. METHOD: In a
      randomised, prospective trial comparing nasogastric versus gastrostomy tubes the
      primary endpoint was the subjective inconvenience induced by the tube system and
      was assessed in the context of a standardised face-to-face interview. These
      interviews were tape-recorded on a pocket memo. Two independent raters listened
      to these interviews and judged--on the basis of how the interviewer formulated
      the questions--which treatment arm they thought the patients were assigned to and
      how confident they were in their judgement. RESULTS: The overall proportion of
      correct judgements was 50.5% for rater 1 and 53.2% for rater 2. In other words,
      both judgement performances were not greater than chance. Nevertheless, the
      raters' confidence in their judgements increased significantly ( P<0.05) in the
      course of the rating procedure, whereas the actual proportion of correct
      judgements did not. There was no overlap between the two raters [kappa = 0.022,
      not significant (NS)] and between actual group assignment and both raters'
      judgements (kappa = 0.012, NS and kappa = 0.110, NS). CONCLUSION: The two
      independent raters were not able to detect systematic variations in the
      interviewing style that were contingent on treatment arm assignment. This gives
      further credence to the results of the randomised trial showing greater patient
      reported discomfort and inconvenience with the nasogastric tube than with the
      gastrostomy tube. The present report describes a feasible method to monitor
      subtle biases that may occur in trial settings. This helps to strengthen the
      design of randomised clinical trials in surgery.

PMID- 14586663
TI  - Plasma adiponectin response to acute exercise in healthy subjects.
AB  - Adipose tissue secretes adiponectin, an adipocytokine that is involved in the
      regulation of insulin sensitivity. Following acute exercise, insulin sensitivity
      has been shown to increase. Increased adiponectin following exercise may be
      related to the change in insulin sensitivity. The purpose of the present study
      was to characterize the effect of a single cycle exercise session on adiponectin
      and to compare the exercise effects between healthy male and female subjects.
      Plasma concentrations of adiponectin, tissue necrosis factor-alpha (TNF-alpha),
      insulin, glucose, and leptin were assessed before and immediately after a 60
      minute stationary cycle ergometry session at 65% of Vdot;O(2max). Male and female
      subjects were matched for cardiorespiratory fitness and body composition and
      dietary intake was controlled for the three days prior to the exercise trial. At
      rest, adiponectin concentration was not associated with percentage body fat, body
      mass index (BMI), fitness, or resting plasma variables ( P>0.05). Following
      exercise, neither male nor female subjects exhibited changes in adiponectin or
      leptin concentrations ( P>0.05). TNF-alpha exhibited a time main effect increase
      with exercise ( P<0.05), but there were no gender differences. These results
      suggest that plasma adiponectin concentrations do not change with exercise in
      healthy male or female subjects. Results are given as mean (SE).

PMID- 14586664
TI  - Accidental intrathecal mercury application.
AB  - The authors present a case of accidental intrathecal mercury application. A 69
      year-old white woman was admitted to our department with suspected meningitis
      following surgery for spinal stenosis at another hospital. Postoperatively, she
      had developed a cerebro-spinal fluid (CSF) fistula with a subcutaneous cavity.
      Local wound irritation had been suspected and, unfortunately, mercury-containing
      disinfectant was injected into the cavity. Within 24 h the patient demonstrated
      acute neurological deterioration due to meningitis and encephalitis and was
      admitted to our clinic with suspected meningitis due to postoperative CSF
      fistula. Lumbar puncture revealed desinfectant-stained, non-bloody CSF, while
      lumbar MRI demonstrated the large lumbar subcutaneous cavity. Additionally, CSF
      fistula was visualized on MRI. Laboratory examination revealed extremely high
      mercury levels in CSF, blood and urine. Treatment consisted in insertion of a
      lumbar drainage to wash out the mercury. The patient underwent medical
      detoxication using chelating agents (DMPS: RS-2,3-dimercapto-1-propansulfonacid,
      DMSA: meso-2,3-dimercaptosuccinatacid). Surgery was performed in order to close
      the cavity and the fistula. Postoperatively, the patient was admitted to the
      intensive care unit and remained intubated for 3 days. Within 4 weeks after
      surgery, she demonstrated good recovery. Eighteen months after intoxication,
      polyneuropathy and slight neuropsychological deficiencies were detectable.

PMID- 14586665
TI  - The role of radiofrequency in the treatment of mechanical pain of spinal origin.
AB  - Radiofrequency (RF) ablation is a method that has been gaining popularity over
      the past few years among spinal surgeons. It has a role when dealing with pain of
      spinal origin, either mechanical or neuropathic, after conservative treatment has
      failed. In the present study, 122 patients with a minimal follow up of 1 year
      were examined at our institution after having undergone RF heat lesion of the
      medial branch for mechanical spinal pain (low back pain, thoracic pain or
      cervical pain). They were followed up 1, 3, 6 and 12 months after treatment.
      Twenty-two of them were additionally followed up at 18 months. After 1 month, 91
      patients (75%) were satisfied with the results. After 3 months, 87 patients (71%)
      had significant pain relief, while in 35 patients (29%) there was no improvement.
      After 6 months of follow-up, 80 patients (66%) had pain relief and in 42 patients
      (34%) there was no effect. At 12-months follow-up, 77 patients (63%) showed good
      results and 45 patients (37%) had no effect. In the case of the 22 patients who
      were followed for 18 months, all showed significant pain relief. Minor
      complications occurred in 27 patients (22%), who had transient discomfort and
      burning pain. We concluded that RF is a safe and partially effective procedure
      for mechanical back pain.

PMID- 14586666
TI  - Arbuscular mycorrhizas in a valley-type savanna in southwest China.
AB  - The arbuscular mycorrhizal (AM) status of 67 plant species in a savanna community
      in the hot, dry valley of Jinsha River, southwest China was surveyed. It was
      found that about 95% of the plant species formed AM and 5% possibly formed AM.
      The composition of AM fungi (AMF) in the rhizosphere soils was also investigated.
      The AMF spore density ranged from 5 to 6,400 per 100 g soil, with an average of
      1,530, and these spores/sporocarps were identified as belonging to six genera.
      Fungi belonging to the genera Glomus and Acaulospora were the dominant AMF. High
      densities of AMF spores in the rhizosphere soils, and the intensive colonization
      of the plant roots, indicated that plants grown in this valley-type savanna may
      be highly dependent on AM.

PMID- 14586669
TI  - An operational heat/health warning system in Shanghai.
AB  - Previous research has noted that high surface temperatures within certain
      "offensive" air masses can lead to increased mortality. This study assesses the
      relationship between daily mortality rates and weather within the city of
      Shanghai, China, while introducing an operational heat/health warning system for
      the city. Using numerous meteorological observations, the spatial synoptic
      classification has been used to classify each summer day from 1989 to 1998 into
      one of eight air mass types for Shanghai. Through the comparative analysis of the
      daily air mass type and the corresponding Shanghai mortality rate, "moist
      tropical plus" (MT+), an extremely hot and humid air mass, was identified as an
      offensive air mass with the highest rates of mortality. Using stepwise
      regression, an algorithm was produced to help predict the number of excess deaths
      that will occur with each occurrence of the MT+ airmass. The heat/health warning
      system was run experimentally in the summer of 2001 and illustrated that the use
      of a warning system can alert the city's residents of potentially offensive
      weather situations that can lead to a deterioration in human health.

PMID- 14586667
TI  - Does tumor status influence cancer patients' satisfaction with the doctor-patient
      interaction?
AB  - The interaction of patients with their doctors impacts the experience of disease
      at many levels. It is thus important to measure patient satisfaction with such
      interaction as an outcome of care. Our goal was to investigate whether tumor
      status influences patient satisfaction with interaction with their doctors.
      Specifically, we investigated whether patients with no evidence of disease (NED),
      localized, or metastatic cancers seen in routine follow-up differ in their
      satisfaction with the oncologist. Outpatients attending clinics at a major cancer
      center completed a battery of questionnaires, including the Patient Satisfaction
      with Doctor (PSQ-MD) questionnaire, a 24-item, self-report instrument. It taps
      two facets of the doctor-patient exchange: perceived support and physician
      disengagement. Data concerning tumor status and satisfaction were obtained for
      569 patients, sampled to include equivalent numbers of women and men with breast,
      head and neck, gastrointestinal, genitourinary, or lung cancer, or lymphoma.
      Controlling for age, marital status, annual family income, stressful life events,
      and employment status, patients with metastatic disease felt somewhat less
      supported by their physicians (mean=3.26+/-0.06) than those with localized
      disease (mean=3.42+/-0.04) or NED (mean=3.42+/-0.03), (analysis of covariance, p<
      0.05). Physician disengagement did not differ across the groups (means=1.54+/
      0.06, 1.43+/-0.04, and 1.47+/-0.03 respectively). These findings were consistent
      across cancer diagnoses. Patients with metastatic disease may feel less physician
      support than those with less advanced cancers. Increasing attention to
      satisfaction of different patient groups can pave the way to improved quality of
      care.

PMID- 14586671
TI  - Diabetes mellitus after kidney transplantation in pediatric recipients.

PMID- 14586673
TI  - A case of osteopoikilosis coexisting with amyloidosis of familial Mediterranean
      fever.

PMID- 14586672
TI  - Thrombotic complications in childhood-onset idiopathic membranous nephropathy.
AB  - While the most common clinical feature of nephrotic syndrome is generalized
      edema, patients are at risk of developing other problems, such as bacterial
      infections, electrolyte abnormalities, and venous thromboses. Adults with
      membranous nephropathy appear to be at the greatest risk for developing
      thromboses, especially renal vein thrombosis. However, the same is not true for
      children with membranous nephropathy. A review of pediatric membranous
      nephropathy stated that renal vein thrombosis is unrecorded in childhood-onset
      membranous nephropathy. We present our experience in managing two children with
      idiopathic membranous nephropathy who developed venous thromboses. To our
      knowledge, this is the first report of pediatric patients with membranous
      nephropathy to develop a thromboembolic complication without evidence of
      predisposing factors or coagulation abnormalities. This report emphasizes the
      need for appropriate evaluation of patients with membranous nephropathy who
      develop signs and symptoms suggestive of arterial or venous occlusion in order to
      avoid missing this potentially life-threatening medical complication.

PMID- 14586674
TI  - Comparison of trained and untrained dog urines.

PMID- 14586675
TI  - Two heterozygous mutations of CLDN16 in a Japanese patient with FHHNC.
AB  - Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC, MIN
      248250) is a rare autosomal recessive tubular disorder that eventually progresses
      to renal failure. However, the progression to end-stage renal failure can vary
      from patient to patient. A primary defect is related to impaired tubular
      resorption of magnesium and calcium in the thick ascending limb of Henle's loop.
      Recently, paracellin-1 was identified as a renal tight junction protein
      predominantly expressed in TAL. Mutations of its gene (CLDN16) have been shown to
      cause FHHNC. We describe a sporadic Japanese case of FHHNC. The male patient
      showed hematuria, hypercalciuria, and nephrocalcinosis at 5 years of age.
      Hypomagnesemia was also noticed at this time. As renal function gradually
      deteriorated, further evaluation was performed at 14 years of age and a diagnosis
      of FHHNC was made. Despite several medications (magnesium supplementation,
      citrate, and hydrochlorothiazide), he eventually progressed to renal
      insufficiency at 19 years of age. Analysis of the CLDN16 gene demonstrated two
      heterozygous mutations (R149Q and R216C). Mutations of the same amino acids have
      already been described in FHHNC and thus these mutations might be the cause of
      the disease in our patient. Hence, we confirm the genetic impairment of the
      CLDN16 gene in a Japanese patient with FHHNC.

PMID- 14586676
TI  - Concurrent poststreptococcal glomerulonephritis and autoimmune hemolytic anemia.
AB  - We describe three cases of poststreptococcal glomerulonephritis (PSGN) associated
      with autoimmune hemolytic anemia. Along with the classic findings of PSGN, the
      patients had a positive direct antiglobulin test. Two patients had a cold
      reacting anti-I autoantibody. This is the first description of this association.
      Autoimmune hemolytic anemia should be considered in children with PSGN and
      significant anemia or signs of hemolysis.

PMID- 14586677
TI  - Sevelamer hydrochloride: an effective phosphate binder in dialyzed children.
AB  - This pilot study was designed to evaluate the efficacy and acceptability of
      sevelamer hydrochloride as a phosphate binder in pediatric patients treated with
      dialysis. A 6-month open-label trial of sevelamer hydrochloride (Renagel) was
      initiated in 17 patients, aged 11.8+/-3.7 years, undergoing hemodialysis ( n=3)
      or peritoneal dialysis ( n=14). Following a 2-week washout period of the
      phosphate binders, serum phosphorus increased from 5.2+/-1.3 mg/dl to 7.5+/-2.2
      mg/dl ( P<0.0002). After initiation of therapy with sevelamer hydrochloride,
      serum phosphorus levels decreased to 6.2+/-1.2 mg/dl ( P<0.01) during the first 8
      weeks and final values were 6.3+/-1.5 mg/dl. Serum calcium concentration
      decreased during the washout period from 9.4+/-0.9 mg/dl to 8.9+/-1.5 mg/dl (
      P<0.01); values remained unchanged thereafter. The serum calcium-phosphorus ion
      product decreased during the first 8 weeks and values did not change
      subsequently. Serum bicarbonate, parathyroid hormone, total cholesterol, low
      density lipoprotein and high-density lipoprotein cholesterol, and triglyceride
      levels did not change. The initial prescribed dose of sevelamer hydrochloride was
      121+/-50 mg/kg (4.5+/-5 g/day) and the final prescribed dose was 163+/-46 mg/kg
      (6.7+/-2.4 g/day). Sevelamer hydrochloride was well tolerated and without adverse
      effects related to the drug.

PMID- 14586678
TI  - Arterial hypertension following renal transplantation in children-a short-term
      study.
AB  - Systemic arterial hypertension is a common complication among transplanted
      patients. The objective of this study was to investigate the risk factors for
      arterial hypertension after kidney transplantation in children. A retrospective
      study was carried out of 70 kidney transplants performed on patients under 18
      years of age at the Hospital do Rim and Hipertensao, from January 1998 to June
      2001. At the end of 6 months post transplant, the patients were classified into
      either normotensive ( n=31) or hypertensive ( n=39) groups. The following
      potential risk factors for arterial hypertension were studied: (1) hypertension
      before transplantation; (2) the glomerular filtration rate (GFR) at 1, 3, and 6
      months post transplant; (3) acute rejection episodes; (4) cumulative dose of
      corticosteroids; (5) the presence of native kidneys; (6) symptomatic renal artery
      stenosis; (7) cold ischemia time greater than 24 h; (8) age and sex of the donor;
      (9) age of the recipient; (10) transplant type (living related or cadaveric
      donor); (11) the body mass index of recipients at the end of the follow-up
      period; and (12) delayed graft function. The two groups were comparable in terms
      of the etiology of renal insufficiency, age, gender, and immunosuppressive drugs.
      Among the risk factors studied, the sole factor showing a statistically
      significant association with arterial hypertension was the GFR at 3 and 6 months
      after transplantation. In the group of normotensive patients, GFRs were 92+/-29
      and 83+/-20 ml/min per 1.73 m(2) at 3 and 6 months, respectively, whereas in the
      hypertensive patients, GFRs were 74+/-23 and 70+/-21 ml/min per 1.73 m(2)
      respectively. Hence, only the lower GFR can be considered a risk factor for
      hypertension in children within our sample. However, arterial hypertension might
      be a risk factor for the early onset of chronic allograft nephropathy; in this
      case, hypertension should be considered the cause of lower glomerular filtration.
      Our data do not permit us to distinguish between these two hypotheses. The known
      risk factors for hypertension following renal transplantation in adults were not
      confirmed in the present study. It remains unclear to us as to whether this means
      the etiology of hypertension differs in children, or if this is the result of a
      bias in patient selection.

PMID- 14586679
TI  - Vesicoureteral reflux in infants with isolated antenatal hydronephrosis.
AB  - Standardized evaluation of all newborns with antenatally recognized
      hydronephrosis (ANH) at The Hospital for Sick Children (HSC) has included voiding
      cystourethrography (VCUG). This paper reviews this protocol to determine: (1) the
      prevalence of vesicoureteral reflux (VUR) in isolated ANH and (2) the value of
      performing VCUG in cases of mild hydronephrosis, defined as renal pelvis
      dilatation <10 mm on postnatal ultrasonography (US). A retrospective chart review
      was performed on infants referred with ANH. The inclusion criterion was isolated
      ANH. Exclusion criteria were (1) presence of additional genitourinary
      abnormalities and (2) no VCUG. Pelviectasis was categorized according to the
      anteroposterior diameter of the renal pelvis. There were 111 infants with
      isolated ANH. All except 3 underwent VCUG. There were 68 children (63%) with
      normal postnatal US or mild pelviectasis (<10 mm). VUR was detected in 16
      patients, of whom 10 had mild or absent pelvic dilatation. There was no
      correlation between the degree of pelviectasis on postnatal US and the presence
      or severity of VUR ( P=0.567 and P=0.802). VUR was detected in 15% of children
      with isolated ANH, many of whom had normal postnatal US or mild postnatal
      pelviectasis. VCUG is the only reliable test for detecting postnatal VUR.

PMID- 14586680
TI  - Catch-up growth with normal parathyroid hormone levels in chronic renal failure.
AB  - The optimum range for parathyroid hormone (PTH) levels in children with chronic
      renal failure (CRF) remains undefined. We aimed to determine growth velocity in
      children with CRF managed with normal PTH levels. We performed a retrospective
      case note review of 99 children (77 boys), with a glomerular filtration rate
      (GFR) <41 ml/min per 1.73 m(2), who had at least 2 years of 3-monthly follow-up.
      The age range at entry was 0.5-6.0 years; data collection was continued until 10
      years of age or the commencement of growth hormone or renal replacement therapy.
      The median GFR was 22 ml/min per 1.73 m(2); over the study period mean serum
      calcium and phosphate levels were approximately equal to the mid-point of the
      respective normal ranges. Median PTH levels were equal to the upper limit of the
      normal range. Height standard deviation score (Ht SDS) at entry was -1.73. During
      the study period the overall mean change in Ht SDS was +0.3, significantly
      greater than the no change expected of a normal population ( P=0.004). The median
      dose of calcium carbonate was 150 mg/kg per day and 1-alpha calcidol 0.015
      microg/kg per day. The growth rate was independent of all parameters, including
      age, PTH levels, the use of enteral feeds, and 1-alpha calcidol prescription. Our
      results indicate that catch-up growth can occur in infants and children with CRF
      when medical therapy is aimed at normalizing PTH levels.

PMID- 14586681
TI  - The effect of hepatitis B vaccination on the incidence of childhood HBV
      associated nephritis.
AB  - The aim of the present study was to investigate the effect of a vaccination
      program for hepatitis B virus (HBV) on the incidence of HBV-associated
      glomerulonephritis (HBV-GN). In total, 727 renal biopsies were carried out at our
      hospital from November 1979 through March 2002. Two groups were established.
      Group A included those biopsied from November 1979 through December 1991 (prior
      to the HBV vaccination program) and group B from January 1992 through March 2002.
      Group B was divided into five subgroups (B(1 )to B(5)), with an interval of 2
      years between each subgroup. Patients were divided into those with or without a
      history of HBV vaccination. Of the 727 renal biopsies, 64 fulfilled the criteria
      of HBV-GN, There were 28 cases of the 211 cases in group A and 36 cases of the
      516 cases in group B ( X(2)=7.397, P<0.01). The incidence in group A and group
      B(1 )through B(5 )was 13.27% (28/211), 13.04% (9/69), 7.32 (6/82), 6.25% (4/64),
      4.88% (4/82), and 5.94% (13/219), respectively ( X(2)=9.627, P<0.01). Only 8 of
      the 231 vaccinated children had HBV-GN, while there were 48 HBV-GN cases of the
      381 non-vaccinated children ( X(2)=14.44, P<0.001). There were only 6 cases of
      membranous nephropathy (MN) in the vaccinated group, while 40 cases of MN
      occurred in the non-vaccinated group ( X(2)=12.92, P<0.01). There were 8 children
      that developed HBV-GN with abnormal serum HBV markers despite HBV vaccination.
      Two mothers of these 8 children had evidence of HBV infection. The incidence of
      HBV-GN in children has been decreasing each year since the implementation of the
      nationwide HBV vaccination program in Shanghai, China. Furthermore, since
      childhood MN is associated with HBV, vaccination can also reduce the incidence of
      childhood MN.

PMID- 14586682
TI  - Benign intracranial hypertension in children following renal transplantation.
AB  - Benign intracranial hypertension (BIH) is a condition characterized by headache,
      papilledema, and a raised cerebrospinal fluid pressure with normal cranial
      imaging. It is uncommon in childhood. Previously, there have been reports that
      children with chronic impairment of renal function may be at greater risk of
      developing BIH. This study involved retrospective case note analysis of children
      undergoing renal transplantation over the last 11 years at our institution. Nine
      children developed BIH after renal transplantation. The prevalence of the
      condition in our series was 4.4%. Several etiologically relevant risk factors
      were identified, including medication (nitrofurantoin, minocycline) and excess
      weight gain. Our results suggest that BIH may be a more frequent complication of
      the post-operative care of pediatric renal transplant recipients than previously
      thought. We hope to alert pediatric nephrologists that examination of the fundus
      for papilledema in all renal transplant patients complaining of headache is
      essential. If the diagnosis of BIH is delayed, irretrievable visual loss may not
      be avoided.

PMID- 14586683
TI  - Relationship of leptin and insulin-like growth factor I to nutritional status in
      hemodialyzed children.
AB  - Malnutrition is prevalent in patients with end-stage renal disease (ESRD).
      Elevated serum leptin levels were thought to contribute to the anorexia and poor
      nutrition in renal failure. However, studies of the relationship between
      nutritional status and leptin concentration in chronic renal failure have yielded
      conflicting results. Plasma insulin-like growth factor I (IGF-I) level has been
      used as an indicator of nutritional status in patients with renal failure. The
      relationship between leptin and IGF-I is controversial. The present study was
      conducted with the aim of assessing the relationship between nutritional status,
      hyperleptinemia, and serum IGF-I. Seventeen ESRD patients (8 male, 9 female),
      aged 8-18 years (mean 15.3+/-3.3 years) and undergoing standard hemodialysis for
      58.8+/-23.1 months were enrolled. Nine age-matched healthy children served as
      controls. In all patients, energy and protein intakes were 40-70 kcal/kg per day
      and 1-1.54 g/kg per day, respectively. Predialysis serum leptin and IGF-I levels
      were measured by radioimmunoassay. Body mass index was decreased in 13 (76%)
      patients. Triceps skinfold thickness (TST) was reduced (below the 5th percentile)
      in 7 (41%), whereas mid arm circumference and mid arm muscle circumference were
      reduced in 14 (82.5%) and 13 (76.5%), respectively. The median serum leptin level
      was significantly higher in patients than in controls [13.7 interquartile range
      (IQR) 30.50 pg/ml vs. 6.50 IQR 8.65 pg/ml, P=0.01]. The median serum IGF-I level
      was lower in the patients (205.1 ng/ml IQR 194.4 ng/l) than controls (418.0 ng/l
      IQR 310.5 ng/ml) ( P=0.01). IGF-I levels were more decreased in patients with
      severe malnutrition, defined according to TST (145.0 ng/ml IQR 125.5 ng/l) than
      patients without malnutrition (301.2 ng/l IQR 218.8 ng/ml) ( P=0.03) and healthy
      children ( P=0.002). Although statistically not significant, IGF-I levels tended
      to be decreased, while leptin levels were increased. The median plasma insulin
      concentration was 15 microU/ml (1.63-45.80) and did not correlate with leptin and
      IGF-I levels. In conclusion, the results of this study confirm the presence of
      high circulating plasma leptin levels, which may be one of the many factors
      involved in the pathogenesis of the malnutrition in children on hemodialysis.

PMID- 14586684
TI  - Renal failure in Nigerian children: factors limiting access to dialysis.
AB  - A 5-year clinical and laboratory study of Nigerian children with renal failure
      (RF) was performed to determine the factors that limited their access to dialysis
      treatment and what could be done to improve access. There were 48 boys and 33
      girls (aged 20 days to 15 years). Of 81 RF patients, 55 were eligible for
      dialysis; 33 indicated ability to afford dialysis, but only 6 were dialyzed, thus
      giving a dialysis access rate of 10.90% (6/55). Ability to bear dialysis
      cost/dialysis accessibility ratio was 5.5:1 (33/6). Factors that limited access
      to dialysis treatment in our patients included financial restrictions from
      parents (33%), no parental consent for dialysis (6%), lack or failure of dialysis
      equipment (45%), shortage of dialysis personnel (6%), reluctance of renal staff
      to dialyze (6%), and late presentation in hospital (4%). More deaths were
      recorded among undialyzed than dialyzed patients ( P<0.01); similarly, undialyzed
      patients had more deaths compared with RF patients who required no dialysis (
      P<0.025). Since most of our patients could not be dialyzed owing to a range of
      factors, preventive nephrology is advocated to reduce the morbidity and mortality
      from RF due to preventable diseases.

PMID- 14586686
TI  - Colchicine therapy in amyloid nephropathy due to recessive dystrophic
      epidermolysis bullosa.

PMID- 14586685
TI  - Calcimimetic agents and secondary hyperparathyroidism: rationale for use and
      results from clinical trials.
AB  - Calcimimetic agents are small organic molecules that act as allosteric activators
      of the calcium sensing receptor (CaSR). In parathyroid cells, they lower the
      threshold for receptor activation by extracellular calcium ions and diminish
      parathyroid hormone (PTH) secretion. Calcimimetic compounds thus represent a
      novel way of controlling excess PTH secretion in clinical disorders such as
      secondary hyperparathyroidism (SHPT) due to chronic renal failure. Clinical
      trials have documented that the calcimimetic agent cinacalcet hydrochloride
      effectively lowers plasma PTH levels without increasing serum calcium or
      phosphorus concentrations in adult hemodialysis patients with SHPT. Serum
      phosphorus levels and values for the calcium-phosphorus ion product in serum
      often decline as plasma PTH levels fall during treatment. Experimental evidence
      suggests that calcimimetic agents may also impede the development of parathyroid
      gland hyperplasia, an integral component of SHPT due to chronic renal failure.
      Calcimimetic agents have considerable potential, therefore, as part of new
      therapeutic strategies for SHPT.

PMID- 14586687
TI  - Laparoscopic approach to the management of intraabdominal unicentric Castleman's
      disease.
AB  - Castleman's disease, or angiofollicular lymphoid hyperplasia, is a rare
      lymphoproliferative disorder of unknown etiology. We present the case of an 18
      year-old woman who was admitted with symptoms of fatigue, weakness, early
      satiety, and weight gain. A subhepatic mass anterior to the pancreas was
      discovered on ultrasound. After being treated via the laparoscopic approach with
      complete surgical resection she recovered well. This case thus represents a new
      application for laparoscopy and expands the indications for its use.

PMID- 14586688
TI  - Development of a quantification system of ionic dissociative metabolites using an
      FT-IR/ATR method.
AB  - A simultaneous quantification system of ionic dissociative metabolites was
      developed using a Fourier transform mid-infrared spectroscopic method by focusing
      our attention on the enzyme reaction from glucose 6-phosphate to fructose 6
      phosphate with phosphoglucose isomerase (PGI). We studied the pH dependency of
      the infrared spectra of the mixture solution for which the PGI reaction was
      assumed. The infrared spectra of ionic dissociative components in the mixture
      solution were extracted by multiple linear regression analysis under the
      assumption of ionic dissociation equilibrium. Additionally, we constructed a
      simultaneous quantification system using the extracted spectra of the ionic
      dissociative components on the basis of the ionic dissociation equilibrium. We
      could accurately estimate the pH value and the concentrations of the ionic
      dissociative materials in their mixture solution by using this quantification
      system. In addition, the stability of quantification results for a pK shift was
      also verified.

PMID- 14586689
TI  - The evolution of placental mammal body sizes: evolutionary history, form, and
      function.
AB  - The unimodal, right-skewed distribution, most frequently identified in
      contemporary descriptions of placental mammal body size distributions, masks an
      underlying multidistribution structure; a long-term evolutionary process that has
      generated a concatenation of two or three frequency distributions specific to
      locomotory modes (plantigrade, digitigrade and unguligrade). The Afrotropical
      assemblages are bimodal, with a tendency towards trimodality, whereas the
      Nearctic assemblage is unimodal. However, mixtures of two and three normal
      distributions fitted the Nearctic data well, suggesting a multidistribution
      structure masked by disproportionate species numbers within locomotory modes.
      Differences in proportional species numbers within modes between assemblages may
      reflect the evolutionary history of form and function. However, common
      interassemblage predictions of such proportions in contemporary distributions may
      be disguised by the relative severity of the Pleistocene megafaunal extinction
      (patterns supported by the fossil record), geographical scale, and taxonomic
      composition. A species gap occurs at body sizes around 1 kg at the interface
      between the largest plantigrade mammals and the smallest digitigrade mammals,
      coincident with the minimum interspecific variance of basal metabolic rate. In
      terms of the evolution of the optimal body size in the trade-off between
      mortality and production, there may be good historical and evolutionary reasons
      why we should not expect optimization to produce the same results in different
      zoogeographical assemblages. Moreover, the evolution of diverse mammalian forms
      and functions, especially with respect to predator-prey interactions and diet,
      render a single body size optimum untenable in the search for an energetic
      definition of fitness.

PMID- 14586690
TI  - Calbindin-D9k (CaBP9k) localization and levels of expression in trophoblast cells
      from human term placenta.
AB  - During pregnancy, the calcium (Ca(2+)) transport machinery of the placenta is
      solely responsible for the nutrient supply to the developing fetus, where active
      Ca(2+) transport occurs from the mother to the fetus. As part of a larger study
      to determine the role of Ca(2+) in placental transport in vivo, we questioned
      whether calbindin-D9k (CaBP9k), which is mainly expressed in duodenum, uterus,
      and placenta of several mammals, is present in cytotrophoblast cells and
      syncytiotrophoblasts of human term placenta. We were interested in this protein
      because of its potential importance in serving as an indicator of Ca(2+)
      availability and utilization in the placenta. Here, we demonstrated that CaBP9k
      transcript is present in both cell types, with a lower expression in
      cytotrophoblast cells as compared to syncytiotrophoblasts. Moreover, we showed by
      immunochemistry that CaBP9k protein was present in cytotrophoblast and
      syncytiotrophoblast placental tissue sections as well as in cultured cells. The
      occurrence of CaBP9k protein in trophoblast cells was further confirmed by
      Western blot analysis. Thus, these results indicate for the first time that
      CaBP9k is unequivocally expressed by trophoblast cells from human term placenta.

PMID- 14586691
TI  - Cutaneous eccrine glands of the foot pads of the small Madagascan tenrec (
      Echinops telfairi, Insectivora, Tenrecidae): skin glands in a primitive mammal.
AB  - In order to find correlations between skin gland morphology and specific
      ethological features, the cutaneous glands of the foot pads of the primitive
      mammal the Madagascan tenrec, Echinops telfairi, were studied by histological and
      various histochemical methods as well as by electron microscopy. In the foot pads
      specific eccrine skin glands occurred consisting of coiled ducts and tubular
      secretory portions, the lumina of which were considerably wider than in primate
      sweat glands. The secretory tubules were composed of branched myoepithelial cells
      and glandular cells. The latter contained abundant mitochondria, large amounts of
      glycogen particles and few secretory granules as well as individual
      heterolysosomes and myelin bodies. The lateral cell membrane was marked by
      extensive interdigitations. The apical membranes of all glandular cells contained
      proteoglycans with sulfated and carboxylated groups containing N-acetyl
      glucosamine, N-acetyl-galactosamine, galactose and mannose. The expression
      pattern of cytokeratins of the glandular epithelium was variable and showed
      similarities to that of the human eccrine glands. Tubulin, vinculin and actin
      were expressed in the glandular epithelium. The secretory cells showed positive
      reactions with antibodies against antimicrobial peptides and IgA. A positive
      reaction was observed with antibodies against the androgen receptor. The PCNA and
      TUNEL reactions indicated that the tubular skin glands of Echinops are made up of
      a slowly renewing tissue. We conclude that the glands fulfill several functions:
      production of a fluid-rich secretory product, which may prevent slipping of the
      foot pads on the substrate during running or climbing, secretion of antimicrobial
      peptides and proteins, and playing a role in thermoregulation.

PMID- 14586692
TI  - The role of epithelial remodelling in tooth eruption in larval zebrafish.
AB  - Based on light and transmission electron-microscopic observations on erupting
      first-generation teeth in the zebrafish, Danio rerio, we propose a biphasic
      mechanism for tooth eruption: (1). formation of an epithelial crypt prior to
      eruption of the tooth, possibly as a result of constraints in the epithelium
      resulting from the growth of adjacent tooth germs, and (2). detachment of
      cellular interdigitations both within the pharyngeal epithelium, at the
      pharyngeal epithelium/enamel organ boundary, and between the outer and inner
      dental epithelium, resulting in the exposure of the tooth tip in the crypt,
      immediately after tooth ankylosis. Later, further detachment of interdigitations
      between the inner and the outer enamel epithelium unfolds the epithelium even
      more and leads to a more pronounced exposure of the tooth tip. The presence of
      small patches of non-collagenous matrix on the outer surface of the tooth close
      to where it merges with the attachment bone is interpreted as a device to prevent
      complete detachment of the enamel organ. The biphasic nature of the mechanism for
      tooth eruption is supported by observations on in vitro cultured heads. First
      generation teeth develop normally and crypts are formed, as under in vivo
      conditions, but the teeth fail to erupt. Taken together, our observations suggest
      that epithelial remodelling plays a crucial role in eruption of the teeth in this
      model organism.

PMID- 14586693
TI  - Biphasic constitutive laws for biological interface evolution.
AB  - A model of tissue differentiation at the bone-implant interface is proposed. The
      basic hypothesis of the model is that the mechanical environment determines the
      tissue differentiation. The stimulus chosen is related to the bone-implant
      micromotions. Equations governing the evolution of the interfacial tissue are
      proposed and combined with a finite element code to determine the evolution of
      the fibrous tissue around prostheses. The model is applied to the case of an
      idealized hip prosthesis.

PMID- 14586694
TI  - A description of arterial wall mechanics using limiting chain extensibility
      constitutive models.
AB  - Certain aspects of the mechanical response of arterial walls can be described
      using nonlinear elasticity theory. Uniaxial tests on vascular walls reveal
      nonlinear stress-strain behavior, with higher extensibility in the low stretch
      range and progressively lower extensibility with increasing stretch. This
      phenomenon is well known in the framework of rubber-like materials where it is
      called a strain-hardening or strain-stiffening effect. Constitutive models of
      incompressible hyperelasticity that take this into account include power-law
      models and limiting chain extensibility models. Our purpose in this paper is to
      bring to the attention of the biomechanics community some essential features of
      one such model of the latter type due to Gent. This model is compared with
      isotropic versions of biomechanical constitutive models by Takamizawa-Hayashi and
      Fung; the latter is a limiting version of a power-law material. Two particular
      problems are considered for which experimental data on arterial wall deformations
      are available. The first concerns small oscillations superposed on a large static
      stretch of a vertical string of arterial tissue. It is shown that the exponential
      model of Fung and the Gent model match well with the experimental data. The
      second problem is the extension of an internally pressurized circular cylindrical
      tube. It is shown that an inversion phenomenon observed experimentally for the
      human iliac artery can be described within a membrane theory by the Gent model
      whereas this cannot be described using the exponential model. The foregoing
      considerations are carried out for isotropic elastic materials in the absence of
      residual stress. Extensions to include anisotropy are also indicated.

PMID- 14586696
TI  - Relationship between structural modeling and hyperelastic material behavior:
      application to CNS white matter.
AB  - Recent measurements of the material properties of brain tissue allow an
      examination of the underlying microstructural basis in both physiological and
      pathophysiological conditions. The purpose of this study is to develop a
      mathematical relationship between microstructurally based models of the central
      nervous system (CNS) white matter and equivalent hyperelastic material models.
      For simplicity, time dependent material behavior is not included in this
      formulation. The microstructural representation is used to formulate structural
      property relationships for highly oriented white matter, and is mathematically
      compared to one isotropic and two anisotropic hyperelastic formulations. For the
      anisotropic characterizations, the population of axons in the white matter is
      assumed to align along one preferred direction of the material, yielding a
      transversely isotropic formulation. Relatively simple strain-energy functions
      incorporating material anisotropy provide sufficient flexibility to model the
      nonlinear behavior predicted from structurally based models, although the
      tangential stiffness of the hyperelastic approaches does not follow completely
      the behavior of the structurally based formulations. This analysis is an initial
      step towards linking microstructural aspects of the tissue to material models
      commonly used for large deformations, and may be an important step in relating
      predicted tissue deformation to the deformation and stress of cellular and
      subcellular structures.

PMID- 14586697
TI  - Size effects in the elasticity and viscoelasticity of bone.
AB  - Size effects of large magnitude are observed in the torsional shear modulus and
      damping of bovine plexiform bone. Damping increases and stiffness decreases with
      specimen size over all sizes studied. Measurements were conducted in torsion
      using a laser-based micromechanics apparatus capable of viscoelastic studies over
      a range of frequencies up to 100 kHz, upon samples of various size, with no
      parasitic friction or other errors that could mimic any size effect. Torsional
      tan delta at 1 Hz varies by about a factor of five over the size range 2.8-6.2 mm
      thick, and is more dependent on specimen thickness at 1 Hz than it is at higher
      frequency. The size effects are attributed to compliance and viscoelasticity of
      the interfaces between laminae. These laminae must be substantially stiffer than
      whole bone. Observed size effects are likely to play a role in understanding
      scaling laws of bones in living organisms.

PMID- 14586695
TI  - Complex distributions of residual stress and strain in the mouse left ventricle:
      experimental and theoretical models.
AB  - Most soft biological tissues, including ventricular myocardium, are not stress
      free when all external loads are removed. Residual stress has implications for
      mechanical performance of the heart, and may be an indicator of patterns of
      regional growth and remodeling. Cross-sectional rings of arrested ventricles
      opened up when a radial cut was made (initial mean opening angles were 64 +/- 17
      degrees), but further circumferential cuts revealed the presence of additional
      residual stresses in the tissue with further opening of the rings. In normal
      mouse hearts, the inner half of a short-axis ring opened more than the outer
      half, and this change was dependent on apex-base location. At the apex the inner
      section vs. outer section opening angles were 226 +/- 47 degrees vs. 89 +/- 28
      degrees, while at the base the same two angles were 160 +/- 30 degrees vs. 123 +/
      35 degrees. A simple theoretical cylindrical shell model with incompressible
      hyperelastic material properties was used to model the experimental deformations
      based on the cutting experiments. The model predicts different residual stress
      fields depending on the nature of the opening after the circumferential cut
      (which is done after the conventional radial cut). The observed opening angles
      were consistent with steep stress gradients near the endocardium compared with
      those predicted if the first cut was assumed to relieve all residual stresses.
      These results imply a more complex distribution of residual stress and strain in
      ventricular myocardium than previously thought.

PMID- 14586698
TI  - Numerical simulation of the superplastic forming of dental and medical
      prostheses.
AB  - A relatively recent development in prostheses manufacture is the use of
      superplastic forming technology formerly associated with industrial applications
      such as aerospace components. This paper considers the finite element incremental
      flow formulation for the simulation of the forming of thin and moderately thick
      titanium alloy sheet dental and medical prostheses and, in particular, the
      determination of the pressure-time cycle. Issues concerning material
      characteristics are discussed, and the process is illustrated by a number of
      examples. The application of finite element simulation in this context is
      ongoing, nevertheless interim conclusions are drawn and future directions for
      research are identified.

PMID- 14586699
TI  - Strain measurement in biaxially loaded inhomogeneous, anisotropic elastic
      membranes.
AB  - This paper considers the problem of measuring the strain field in biaxially
      loaded elastic membranes, such as soft biological tissue. Cross-correlation of
      intrinsic or applied speckle patterns were used to calculate the 2D displacements
      of small regions on the surface of a deforming membrane. This method was able to
      resolve 2D displacements to within a twentieth of a pixel. A finite-element model
      with bicubic-Hermite interpolation was used to represent the geometry of the
      membrane in the undeformed state. This model was fitted to the measured
      displacements to obtain the geometry of the membrane in the deformed state, and
      the strain field was calculated from the change in geometry. The strain fields
      were measured in both an inhomogeneous isotropic rubber membrane and a section of
      sheep diaphragm.

PMID- 14586700
TI  - Instrumentation and procedures for estimating the constitutive parameters of
      inhomogeneous elastic membranes.
AB  - This study presents a method for estimating the spatial variations in material
      properties of elastic membranes, such as biological tissue, which contain both
      inhomogeneous strain fields and inhomogeneous material properties. In order to
      validate the method, an inhomogeneous, isotropic rubber membrane was biaxially
      loaded to obtain a set of states. A neo-Hookean finite element model, together
      with the measured strains, was used to estimate the material parameters by
      minimizing the residuals between the measured and modelled residual on surface
      tractions.

PMID- 14586701
TI  - Mechanobiology of cartilage: how do internal and external stresses affect
      mechanochemical transduction and elastic energy storage?
AB  - Articular cartilage is a multilayered structure that lines the surfaces of all
      articulating joints. It contains cells, collagen fibrils, and proteoglycans with
      compositions that vary from the surface layer to the layer in contact with bone.
      It is composed of several zones that vary in structure, composition, and
      mechanical properties. In this paper we analyze the structure of the
      extracellular matrix found in articular cartilage in an effort to relate it to
      the ability of cartilage to store, transmit, and dissipate mechanical energy
      during locomotion. Energy storage and dissipation is related to possible
      mechanisms of mechanochemical transduction and to changes in cartilage structure
      and function that occur in osteoarthritis. In addition, we analyze how passive
      and active internal stresses affect mechanochemical transduction in cartilage,
      and how this may affect cartilage behavior in health and disease.

PMID- 14586703
TI  - Force and deformation on branching rudiments: cleaving between hypotheses.
AB  - A mathematical model of the forces and deformations of the tissues involved in
      branching morphogenesis is developed and solved. The epithelium and mesenchyme
      are modeled as Stokes fluids separated by an interface. Each fluid is assumed to
      have constant viscosity. An initially 3-lobed rudiment is deformed by three
      inwardly directed point forces. Relationships between the physical parameters of
      the model (tissue viscosity, clefting force, surface tension) and the time course
      and morphology are explored. We find that the surface tension, clefting force,
      and viscosity ratio of the two tissues have significant effects on the branching.
      We conclude that epithelial branching in soft gels is fundamentally different
      from epithelial branching in mesenchyme, because of the different mechanics. We
      propose that a complete understanding of branching morphogenesis requires
      measurements of the mechanical aspects.

PMID- 14586704
TI  - A possible role of initial cell death due to mechanical stretch in the regulation
      of subsequent cell proliferation in experimental vein grafts.
AB  - The proliferation of vascular cells contributes to the formation of neointima and
      hypertrophy of the blood vessel wall. Here we show that mechanical stretch
      possibly regulates the proliferation of vascular cells via the mediation of cell
      death in a rat vein graft model. The wall of vein grafts is subject to a suddenly
      increased mechanical stretch due to exposure to arterial blood pressure. Such a
      stretch induces rapid cell death with a reduction in cell density by
      approximately 60% within the first day after surgery. The initial cell death was
      followed by an increase in the percentage of proliferating cells, as shown by a
      BrdU incorporation assay (1.55 +/- 1.27%, 8.48 +/- 2.27%, 11.93 +/- 2.36%, 6.36
      +/- 1.77%, and 5.60 +/- 1.46% at days 1, 5, 10, 20, and 30, respectively). When
      mechanical stretch was reduced by restraining the vein graft using a
      polytetrafluoroethylene sheath, the percentage of proliferating cells reduced
      significantly (0.76 +/- 0.76%, 1.70 +/- 0.46%, 1.29 +/- 0.56%, 0.99 +/- 0.83%,
      and 0.47+/-0.52% at days 1, 5, 10, 20, and 30, respectively). A further reduction
      in cell density, induced by local administration of a cell death inducer ceramide
      to experimental vein grafts (without sheath), enhanced subsequent cell
      proliferation. In contrast, a prevention of cell death, induced by local
      administration of a cell death inhibitor tetrapeptide-aldehyde DEVD-CHO to
      experimental vein grafts (without sheath), significantly reduced subsequent cell
      proliferation. These results suggest that mechanical stretch induces cell death,
      which possibly mediates subsequent cell proliferation in the present model.

PMID- 14586705
TI  - Theoretical and experimental study of growth and remodeling in the developing
      heart.
AB  - A theoretical model is presented for growth and remodeling in the developing
      embryonic heart. The model is a thick-walled tube composed of two layers of
      orthotropic pseudoelastic material. The analysis includes stress and strain
      dependent volumetric growth, with changes in material properties specified to
      reflect the evolving structure of the heart wall. For use in model validation,
      experimental measurements of ventricular opening angles are reported for 3-4-day
      old chick embryos under control and pressure overload conditions. Owing to
      changes in residual stress in the overloaded heart, the opening angle decreased
      from 31 +/- 10 degrees to -8 +/- 12 degrees (mean +/- SD) within 12 h and then
      increased slightly. The opening angle at 12 h was significantly less than the
      control value. With an appropriate choice of parameters, the model yields
      reasonable agreement with these and other published opening angle data, as well
      as with temporal changes in lumen radius, wall thickness, epicardial strains, and
      pressure-volume curves during development before and after birth.

PMID- 14586706
TI  - Application of nonlinear viscoelastic models to describe ligament behavior.
AB  - Recent experiments in rat medial collateral ligament revealed that the rate of
      stress relaxation is strain dependent and the rate of creep is stress dependent.
      This nonlinear behavior requires a more general description than the separable
      quasilinear viscoelasticity theory commonly used in tissue biomechanics. The
      purpose of this study was to determine whether the nonlinear theory of Schapery
      or the modified superposition method could adequately model the strain-dependent
      stress-relaxation behavior of ligaments. It is shown herein that both theories
      describe available nonlinear experimental ligament data well and hence can
      account for both elastic and viscous nonlinearities. However, modified
      superposition allows for a more direct interpretation of the relationship between
      model parameters and physical behavior, such as elastic and viscous
      nonlinearities, than does Schapery's theory. Hence, the modified superposition
      model is suggested to describe ligament data demonstrating both elastic
      nonlinearity and strain-dependent relaxation rate behavior. The behavior of the
      modified superposition model under a sinusoidal strain history is also examined.
      The model predicts that both elastic and viscous behaviors are dependent on
      strain amplitude and frequency.

PMID- 14586707
TI  - Isotonic biaxial loading of fibroblast-populated collagen gels: a versatile, low
      cost system for the study of mechanobiology.
AB  - We developed a simple, versatile system for applying a range of biaxial loads to
      cell-matrix constructs for the study of mechanobiology. The system consists of
      porous polyethylene bars that are polymerized into a square fibroblast-populated
      gel and loaded by freely hanging weights attached to sutures routed through a
      custom loading rig. The cost to manufacture each mold/loading rig pair was less
      than US dollars 250 and the expected life of the components is up to 10 years.
      Neonatal and adult cardiac fibroblasts contracted gels to a decreasing extent as
      external load was increased ( P=0.003) and achieved contraction forces of up to
      1.4 mN per million cells. Strain distributions were reasonably homogeneous in the
      central region of the gel (25% of gel area), but clearly nonhomogeneous outside
      that central region. The primary advantages of this system are simplicity, low
      cost, biaxial loading, and the ability to test for a dose-response effect of
      mechanical load. The current disadvantages are the inability to apply cycling
      loading and the inhomogeneities introduced by the use of rigid loading bars.

PMID- 14586708
TI  - Mechanobiology of engineered cartilage cultured under a quantified fluid-dynamic
      environment.
AB  - Natural cartilage remodels both in vivo and in vitro in response to mechanical
      forces and hence mechanical stimulation is believed to have a potential as a tool
      to modulate extra-cellular matrix synthesis in tissue-engineered cartilage. Fluid
      induced shear is known to enhance chondrogenesis on animal cells. A well-defined
      hydrodynamic environment is required to study the biochemical response to shear
      of three-dimensional engineered cell systems. We have developed a perfused-column
      bioreactor in which the culture medium flows through chondrocyte-seeded porous
      scaffolds, together with a computational fluid-dynamic model of the flow through
      the constructs' microstructure. A preliminary experiment of human chondrocyte
      growth under static versus dynamic conditions is described. The median shear
      stress imposed on the cells in the bioreactor culture, as predicted by the CFD
      model, is 3 x 10(-3) Pa (0.03 dyn/cm(2)) at a flow rate of 0.5 ml/min
      corresponding to an inlet fluid velocity of 44.2 mum/s. Providing a fluid-dynamic
      environment to the cells yielded significant differences in cell morphology and
      in construct structure.

PMID- 14586709
TI  - Estimation of the effective transversely isotropic elastic constants of a
      material from known values of the material's orthotropic elastic constants.
AB  - A method is illustrated for determining the effective transversely isotropic (or
      isotropic) elastic constants from measured orthotropic elastic constants. This
      method consists of constructing upper and lower bounds on the effective
      transversely isotropic (or isotropic) elastic constants using the known
      orthotropic values. This method is illustrated using three sets of elastic
      constants for bone. Fortunately, the upper and lower bounds are very close. Thus
      very good approximations for the effective transversely isotropic (or isotropic)
      elastic constants for cortical and cancellous bone are obtained from previously
      published data on the orthotropic elastic constants for those tissue types. This
      work is undertaken to build a greater database for the transversely isotropic
      elastic constants of bone with the intention of employing them in a transversely
      isotropic model of bone poroelasticity. An interesting aspect of the present
      result is that the Voigt and Reuss bounds are very tight for these anisotropic
      materials. This is not always the case for these bounds.

PMID- 14586710
TI  - Models of cytoskeletal mechanics of adherent cells.
AB  - Adherent cells sense their mechanical environment, which, in turn, regulates
      their functions. During the past decade, a growing body of evidence has indicated
      that a deformable, solid-state intracellular structure known as the cytoskeleton
      (CSK) plays a major role in transmitting and distributing mechanical stresses
      within the cell as well as in their conversion into a chemical response.
      Therefore in order to understand mechanical regulation and control of cellular
      functions, one needs to understand mechanisms that determine how the CSK changes
      its shape and mechanics in response to stress. In this survey, we examined
      commonly used structurally based models of the CSK. In particular, we focused on
      two classes of these models: open-cell foam networks and stress-supported
      structures. We identified the underlying mechanisms that determine deformability
      of those models and compare model predictions with data previously obtained from
      mechanical tests on cultured living adherent cells at steady state. We concluded
      that stress-supported structures appear more suitable for describing cell
      deformability because this class of structures can explain the central role that
      the cytoskeletal contractile prestress plays in cellular mechanics.

PMID- 14586711
TI  - A new model of neurogenic hypertension caused by renal injury: pathophysiology
      and therapeutic implications.
AB  - Increasing evidence indicates that afferent impulses from injured kidney may
      activate areas of the brain involved in the noradrenergic regulation of blood
      pressure and largely contribute to the development and maintenance of
      hypertension associated with renal diseases. A new model of hypertension
      developed in our laboratory by an intrarenal injection of phenol has largely
      substantiated this hypothesis. Our studies also provide evidence that complex
      interactions exist between interleukin (IL)-1Beta and nitric oxide in the
      regulation of central sympathetic nervous system (SNS) activity and blood
      pressure. Following renal injury with phenol, the abundance of IL-1Beta and
      neuronal isoform of nitric oxide synthase (nNOS) in the brain decreased, and this
      may mediate the rise in SNS activity. Finally, our studies provide evidence that
      locally produced angiotensin II in the brain may ultimately mediate the
      downregulation of IL-1Beta and nNOS and result in increased SNS activity and
      hypertension in the phenol-renal-injury model.

PMID- 14586712
TI  - Role of angiotensin II and endogenous vasodilators in the control of glomerular
      hemodynamics.
AB  - The balance of vascular tone between afferent (Af-) and efferent arterioles (Ef
      Arts) is a crucial determinant of glomerular hemodynamics. Thus, to understand
      renal physiology and pathophysiology it is important to study the mechanisms that
      control their vascular resistance. In order to directly study these mechanisms,
      we have developed several in vitro microperfusion preparations of these
      arterioles, which have the advantage of allowing us to observe the arteriolar
      diameter directly in the absence of systemic hemodynamic and hormonal influences.
      Using these preparations, we have found that angiotensin II (Ang II) causes much
      stronger constriction in Ef- than in Af-Arts and that this difference is mediated
      by nitric oxide (NO)- and prostaglandin (PG)-induced modulation of Ang II action
      in the Af-Art. We have also found that the vasoconstrictor effect of Ang II on Ef
      Arts is modulated by PG produced by the upstream glomerulus. Thus, this may be a
      mechanism whereby the glomerulus controls its own capillary pressure by releasing
      PG and thereby adjusting the resistance of the downstream Ef-Art. In addition, we
      have found that in these arterioles activation of the Ang II type 2 (AT2)
      receptor causes endothelium-dependent vasodilation, which modulates the
      vasoconstrictor action mediated by its type 1 (AT1) receptors. Such modulator
      mechanisms that regulate Af- and Ef-Art tone may play an important role in the
      precise control of glomerular hemodynamics, and their alterations may play a role
      in the pathophysiology of renal diseases, including hypertension. Indeed, we have
      demonstrated that the vasoconstrictor action of Ang II on the Af-Art is
      exaggerated in spontaneously hypertensive rats, an animal model of human
      essential hypertension, due to an impaired function of the AT2 receptor before
      the development of hypertension. Because such exaggerated vasoconstriction leads
      to the elevation of renal vascular resistance (an important pathogenic factor for
      essential hypertension), our findings suggest that impaired function of the AT2
      receptor in Af-Arts may play a role in the pathophysiology of essential
      hypertension.

PMID- 14586713
TI  - Roles of bone marrow cells in glomerular diseases.
AB  - Bone marrow transplantation (BMT) has been used as a tool to investigate various
      roles of bone marrow cells in glomerular diseases. BMT from IgA nephropathy-prone
      mice caused glomerular IgA deposition associated with increased circulating
      macromolecular IgA in normal recipients. Conversely, glomerular mesangial lesions
      of IgA nephropathy-prone mice were markedly diminished by BMT from normal donors,
      and the circulating levels of macromolecular IgA were also decreased in the
      recipients. These data suggest that IgA nephropathy may be a stem-cell disease.
      BMT clearly decreased the glomerular injuries in glomerular diseases other than
      murine IgA nephropathy. Theoretically, one mechanism underlying the therapeutic
      effect of BMT is the replacement of the recipient's destructive immune cells with
      the donor's bone marrow cells. Interestingly, when BMT was performed by using
      bone marrow cells of green fluorescent protein (GFP) transgenic mice to
      investigate the differentiation of bone marrow stem cells in recipients, it was
      revealed that bone marrow-derived cells differentiated into glomerular cells in
      mice receiving BMT. This result suggests an alternative mechanism, in that bone
      marrow cells not only replace harmful immune cells but that they also replenish
      injured glomerular cells in BMT recipients, which results in the repair of
      glomerular lesions after BMT. In addition, the glomerular remodeling could
      participate in maintaining glomerular homeostasis. If the mechanisms of
      glomerular remodeling are investigated, this could offer a new therapeutic
      strategy for the repair of glomerular injuries.

PMID- 14586714
TI  - The nephrotoxicity of Aristolochia manshuriensis in rats is attributable to its
      aristolochic acids.
AB  - BACKGROUND: Although Aristolochia manshuriensis (AM), which was incriminated in
      the Japanese variety of Chinese herbs nephropathy, has been recently shown to be
      nephrotoxic in rats, less is known about whether this toxicity is attributable to
      its aristolochic acids (AA). We compared the renal effect of AM with that of
      Akebia quinata (AQ), which has similar components to AM but is free of AA; we
      also compared this effect of AM with that of pure AA, and studied its possible
      mechanism. METHODS: In study 1, rats were divided into four groups. Each group
      was orally given either 0.4 g of AM, 4 g of AM, or 4 g of AQ per day, or vehicle,
      for 5 days. In study 2, rats were given 4 g of AM (which contained 4 mg of AA),
      or 4 mg of pure AA per day, or vehicle, for 5 days. Renal function, and renal
      histology were evaluated on day 5 in study 1 and on days 1, 3, 5, and 14 in study
      2. In study 2, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick
      end-labeling (TUNEL) and proliferating cell nuclear antigen (PCNA) staining were
      also performed. In study 3, rats were treated in the same way as in study 2, but
      were all killed on day 5. Concentrations of AA (I + II) were measured in serum
      and urine in study 2, and in the kidney, lung, heart, liver, and spleen in study
      3. RESULTS: In study 1, only the rats that received 4 g/day of AM developed
      tubular necrosis, azotemia, proteinuria, and glucosuria. In study 2, both AM- and
      AA-treated rats showed progressive tubular damage, decreased renal function, and
      increased urinary protein excretion. The degree of these alterations was
      comparable in the AM and AA groups. Moreover, the concentrations of AA (I + II),
      in serum, urine, and kidney were also comparable in the AM- and AA-treated rats.
      High levels of AA were detected in the lung and kidney. Apoptotic tubular cells
      increased on day 5 and had decreased by day 14 after the withdrawal of AM or AA.
      Meanwhile, proliferating tubular cells progressively increased from day 3 to day
      14. CONCLUSIONS: Our study indicates that the renal toxicity of AM can be
      attributed to its AA component. Tubular cell apoptosis might be one of the
      mechanisms involved in this renal injury.

PMID- 14586715
TI  - An in vitro evaluation of the glycation potential of a natural disaccharide,
      trehalose.
AB  - BACKGROUND: Glucose, an osmotic agent generally used in continuous ambulatory
      peritoneal dialysis (CAPD) dialysate, has a critical characteristic of forming
      advanced glycation endproducts (AGEs). We undertook this study to investigate
      whether a possible osmotic agent, trehalose, formed fewer AGEs than glucose.
      METHODS: Hemoglobin (Hb), a counter-protein of AGE, was incubated in four kinds
      of medium; glucose-phosphate buffered saline (PBS), autoclaved glucose-PBS,
      trehalose-PBS, and autoclaved trehalose-PBS, for 3, 7, 14, and 30 days,
      respectively. Polymerization of the Hb molecule was detected by sodium
      dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and
      carboxymethylated Hb was detected by Western blotting, using specific mono-clonal
      antibody for carboxymethylated N-terminal valine-Hb (CMV-Hb). RESULTS: PBS
      containing glucose showed bands of polymerized Hb molecule, a phenomenon which
      was markedly exaggerated by autoclaving. Likely, PBS containing glucose showed
      the formation of CMV-Hb in the long incubation of 30 days, and PBS containing
      autoclaved glucose showed accelerated formation of CMV-Hb in an incubation as
      short as 3 days. By contrast, PBS containing trehalose showed much less increase
      in a band of 30 k Dalton and in CMV-Hb formation even in autoclaved medium.
      CONCLUSIONS: Our present in vitro study clearly showed the superior
      characteristic of trehalose to produce fewer AGEs. Based upon the results of this
      study, we propose that the application of trehalose should be considered for CAPD
      solution.

PMID- 14586716
TI  - The involvement of advanced glycation endproducts (AGEs) in renal injury of
      diabetic glomerulosclerosis: association with phenotypic change in renal cells
      and infiltration of immune cells.
AB  - BACKGROUND: Glycation of proteins is regarded as one of the major causes of the
      progression of diabetic nephropathy (DN) and of the phenotypic changes in
      glomerular mesangial cells (MC) and the cellular infiltration that occurs in MC
      from DN. It thus is very important to study the interrelationships and
      interaction between these causes. METHODS: The localization of advanced glycation
      endproducts (AGEs), cytoskeletal proteins, and immune cell infiltration was
      evaluated by immunohistochemical study in patients with DN. RESULTS: N(Epsilon)
      (carboxymethyl)lysine (CML), Alpha-smooth muscle actin (SMA), and low-molecular
      weight caldesmon (L-CLD) were localized in the mesangial area in DN. The
      intensity of mesangial SMA and L-CLD expression was significantly correlated with
      the index of diabetic glomerulosclerosis (IDGS), while the expression of
      pentosidine was correlated with the IDGS and with 24-h urinary protein.
      Pentosidine was localized in glomerular basement membrane (GBM) only in DN and
      had a significant correlation with the mesangial expression of SMA and L-CLD.
      Pyrraline deposition on the tubular basement membrane, and the expression of SMA
      and L-CLD, and the infiltration of immune cells were observed in interstitial
      areas in DN. The intensity of L-CLD expression had a close relationship with
      pyrraline deposition and immune cell infiltration. The expression of SMA and L
      CLD in interstitial areas was significantly correlated with the percent
      interstitial volume. CONCLUSIONS: AGEs are involved in renal injury in DN, and
      their effect is, at least in part, exercised via phenotypic changes in intrinsic
      renal cells and by the infiltration of immune cells.

PMID- 14586717
TI  - Effect of corticosteroid therapy on the progression of IgA nephropathy with
      moderate proteinuria.
AB  - BACKGROUND: In patients with heavy proteinuria, corticosteroid therapy has been
      shown to have favorable effects on the progression of IgA nephropathy. However,
      the efficacy of corticosteroids on the progression of IgA nephropathy with
      moderate proteinuria is still controversial. METHODS: We assessed 45 adult (age,
      18-50 years) patients with moderate proteinuria (0.5-2.0 g daily) and preserved
      renal function, (serum creatinine concentration, < or = 106 micromol/l) who were
      diagnosed as having primary IgA nephropathy between December 1993 and July 1998.
      Twenty-three of the patients were treated with corticosteroids (steroid group),
      and the remaining 22 patients had no steroid treatment (control group). All
      patients were followed up for more than 3 years. RESULTS: There were no
      differences in baseline characteristics between the two groups, except for
      proteinuria. In the steroid group, urinary protein excretion was significantly
      higher than that in the control group. During the follow-up period, urinary
      protein excretion was not changed in the control group. On the other hand, in the
      steroid group, mean urinary protein excretion decreased significantly. Seven
      patients in the control group and 2 patients in the steroid group reached the
      endpoint, which was defined as a 50% increase in serum creatinine concentration
      from baseline. Renal survival curves were significantly different between the two
      groups. A second biopsy was performed in 20 patients who received steroid
      therapy. Mesangial cell proliferation, mesangial matrix increase, and cellular
      crescents were significantly reduced in the second compared with the first biopsy
      specimens. CONCLUSIONS: Steroid therapy is effective in reducing the progression
      of IgA nephropathy with moderate proteinuria.

PMID- 14586718
TI  - Effects of the angiotensin II type 1 receptor antagonist candesartan, compared
      with angiotensin-converting enzyme inhibitors, on the urinary excretion of
      albumin and type IV collagen in patients with diabetic nephropathy.
AB  - BACKGROUND: We previously reported that the angiotensin II type 1 receptor
      antagonist candesartan was effective in reducing blood pressure and
      microalbuminuria in hypertensive patients with diabetic nephropathy after
      angiotensin-converting enzyme (ACE) inhibitors were replaced due to side effects.
      In the present study, the clinical effects of candesartan were investigated and
      compared with ACE inhibitors in patients with stage 2 or 3A diabetic nephropathy,
      mainly with respect to the effects on the urinary excretion of albumin and type
      IV collagen. METHODS: Forty-nine patients (26 males/23 females) with diabetic
      nephropathy (stage 2 or 3A), including normotensive patients, were the study
      subjects. The patients were treated with either an ACE inhibitor (23 patients) or
      candesartan (26 patients) for 11 +/- 3 months. The urinary excretion of albumin
      and urinary type IV collagen was measured. RESULTS: Posttreatment blood pressure
      tended to decrease, but such a decrease did not reach a statistically significant
      level, nor did it show any intergroup difference. The urinary albumin excretion
      was positively correlated with pretreatment mean blood pressure and left
      ventricular mass index, but the urinary type IV collagen excretion did not show
      such correlations. The urinary albumin excretion decreased significantly after
      treatment to a similar extent in both groups, whereas the urinary type IV
      collagen excretion decreased significantly only in the candesartan group.
      CONCLUSION: It was revealed that ACE inhibitors and candesartan reduced urinary
      albumin excretion to a similar extent in patients with diabetic nephropathy. From
      the results of the present study, it is inferred that the renoprotective effect
      of candesartan in diabetic nephropathy may partially differ from that of ACE
      inhibitors.

PMID- 14586719
TI  - Interim evidence of the renoprotective effect of the angiotensin II receptor
      antagonist losartan versus the calcium channel blocker amlodipine in patients
      with chronic kidney disease and hypertension: a report of the Japanese Losartan
      Therapy Intended for Global Renal Protection in Hypertensive Patients (JLIGHT)
      Study.
AB  - BACKGROUND: Insufficiency of renal function and high blood pressure influence
      each other and eventually result in life-threatening endstage renal disease. It
      has been proposed that proteinuria per se is a determinant of the progression of
      chronic kidney disease (CKD). The therapeutic strategy for patients with
      proteinuric CKD and hypertension should therefore be targeted with a view not
      merely toward blood pressure reduction but also toward renoprotection. METHODS:
      We examined the effect of the angiotensin (AT)1 receptor antagonist losartan and
      the calcium channel blocker amlodipine, throughout a period of 12 months, on
      reduction of blood pressure and renoprotection. This was done by assessing
      amounts of urinary protein excretion, serum creatinine (SCr), and creatinine
      clearance (CCr) in patients with hypertension (systolic blood pressure [SBP] > or
      = 140 mmHg or diastolic blood pressure [DBP] > or = 90 mmHg) and CKD (male, body
      weight [BW] > or = 60 kg: 1.5 < or = SCr < 3.0 mg/dl; female or male BW < 60 kg:
      1.3 < or = SCr < 3.0 mg/dl), manifesting proteinuria of 0.5 g or more/day.
      Losartan was administered once daily at doses of 25 to 100 mg/day, and amlodipine
      was given once daily at 2.5 to 5 mg/day. No antihypertensive combination therapy
      was allowed during the first 3-month period. RESULTS: A 3-month interim analysis
      revealed that, despite there being no difference in blood pressure between the
      two groups, there was a significant reduction in 24-h urinary protein excretion
      in the losartan group ( n = 43), but there was no change in the amlodipine group
      ( n = 43). Analysis of stratified subgroups with proteinuria of 2 g or more/day
      and less than 2 g/day showed that losartan lowered proteinuria by approximately
      24% in both subgroups, while amlodipine lowered proteinuria by 10%, but only in
      the subgroup of less than 2 g/day (NS). SCr and CCr did not change throughout the
      period of 3 months in either group. No severe or fatal adverse event was
      experienced in either group during the study period. CONCLUSIONS: Losartan
      appeared to be efficacious for renoprotection in patients with proteinuric CKD
      and hypertension, with the mechanism being independent of its antihypertensive
      action.

PMID- 14586720
TI  - Determinants of prescribed dialysis dose and survival in a cohort of chronic
      hemodialysis patients.
AB  - BACKGROUND: The Determinants of the prescribed dialysis dose have not been well
      studied in a large patient population. Few studies have examined survival rates
      after adjusting for dose determinants. METHODS: Data were obtained from a cohort
      of chronic hemodialysis patients for the period January 1991 through December
      2000. The prescribed dialysis dose was calculated as the dialyzer membrane area
      (m2) times session hours, and was expressed as m2h per week. Determinants of the
      prescribed dialysis dose were examined by multivariate logistic regression
      analysis of baseline clinical and laboratory variables. Survival curves for each
      prescribed dose were calculated by the Kaplan-Meier method. Cox proportional
      hazards analysis was used to evaluate differences in the survival curves after
      adjusting for confounding variables. The delivered dose of dialysis, Kt/V, was
      calculated in a subgroup of the cohort. RESULTS: For 1041 patients receiving
      thrice-weekly dialysis, the mean (SD) dialysis dose was 19.8 (5.8) m2h/week
      (range, 6.3 to 33.0 m2h/week). The significant and independent determinants of
      prescribed dialysis dose were sex, age, diabetes mellitus (DM), body mass index
      (BMI), serum albumin, diastolic blood pressure, serum creatinine, duration of
      dialysis, and comorbidity. The dialysis dose received by women and patients with
      DM was relatively low, even when adjusted for BMI ( P < 0.01 for both). During
      the follow-up period, 463 patients died, 60 underwent renal transplant, and 10
      were transferred away from Okinawa. The hazard ratio (95% confidence interval)
      for death was 1.016 (0.995-1.037; not significant) for the dialysis dose
      (m2h/week) after adjustment for multiple confounding factors. The mean (SD) Kt/V
      was 1.31 (0.28). The hazard ratio (95% confidence interval) for Kt/V > or = 1.31
      vs Kt/V < or = 1.30 was 0.706 (0.553-0.900; P = 0.0049). CONCLUSIONS: The
      prescribed dialysis dose did not significantly influence mortality in our cohort.
      Empirically based prescription practice, such as increasing the prescribed
      dialysis dose in male patients, when the BMI is large, or when serum creatinine
      or diastolic blood pressure is high may explain the relatively good prognosis of
      chronic hemodialysis patients in Japan.

PMID- 14586721
TI  - Prediction of chronic renal allograft dysfunction from evaluations of TGFBeta1
      and the renin-angiotensin system.
AB  - BACKGROUND: Growth factors, cytokines, and the renin-angiotensin system (RAS) are
      involved in chronic allograft dysfunction. However, it is unclear whether
      clinical evaluations of TGFBeta1 and the RAS in longterm stable transplant
      patients can predict the development of chronic allograft dysfunction. METHODS:
      Urinary TGFBeta1 excretion and the response of plasma renin activity (PRA) to
      angiotensin I converting-enzyme inhibition (ACE-I) were prospectively examined in
      transplant patients who had had stable graft function (n = 16) for at least 1
      year after renal transplantation. Four-year follow-up studies were undertaken to
      evaluate the impact of these parameters on the development of chronic allograft
      dysfunction. RESULTS: Urinary TGFBeta1 excretion and PRA response to ACE-I in
      renal transplant patients who developed chronic allograft nephropathy 4 years
      after the evaluations (n = 7) were significantly higher and greater,
      respectively, than these values in those who did not ( n = 9; P < 0.01). If the
      cutoff level for urinary TGFBeta1 excretion was 250 pg/min, the 4-year positive
      predictive value (PPV) with respect to the development of chronic allograft
      nephropathy was 83% and the negative predictive value (NPV) was 78% (sensitivity
      [sen.], 71%; specificity [sp.], 88%). If the cutoff level for PRA at 60 min after
      ACE-I was 4.0 ng/ml per h, the 4-year PPV was 71% and NPV was 75% (sen., 70%;
      sp., 75%). The stable transplant patients with high TGFBeta1 excretion and
      exaggerated PRA response showed significantly higher rates of chronic allograft
      dysfunction than those with low TGFBeta1 excretion and weak PRA response.
      CONCLUSIONS: This study demonstrates that some transplant patients with longterm
      stable graft function show increases in the activities of the TGFBeta system and
      the RAS. Evaluations of urinary TGFBeta1 excretion and PRA response to ACE-I
      present a possibility for predicting the development of chronic allograft
      dysfunction, with significant 4-year predictive values.

PMID- 14586722
TI  - Nephrogenic diabetes insipidus due to hydronephrosis in a patient with a solitary
      kidney.
AB  - A 68-year-old man with a history of nephrectomy of the right kidney was admitted
      to our hospital with a 1-month history of polyuria (> 41 per day). He also
      exhibited hyposthenuria, which was unresponsive to treatment with exogenous
      vasopressin. Radiographic examination revealed partial obstruction of the left
      ureter and moderate hydronephrosis. The cause of the obstruction was cancer of
      the ureter. After drainage using a nephrostomy tube, the polyuria and
      hyposthenuria were gradually resolved. This is the first known case of
      nephrogenic diabetes insipidus due to hydronephrosis in a patient with a solitary
      kidney.

PMID- 14586723
TI  - Glomerulonephritis induced by methicillin-sensitive Staphylococcus aureus
      infection.
AB  - A 57-year-old woman developed exacerbation of atopic dermatitis, fever, and
      nephrotic syndrome with microscopic hematuria. By bacteriological study,
      methicillin-sensitive Staphylococcus aureus (MSSA) was detected from each culture
      of pharyngeal mucus, stool, and blood samples. Renal biopsy specimens showed
      endocapillary proliferative glomerulonephritis with massive IgA deposition in the
      mesangium and along the capillary loops. After antistaphylococcal therapy with
      antibiotics, MSSA was negative for each culture and urinary protein decreased.
      Nine months after the first renal biopsy, a re-biopsy was performed, which
      revealed apparent disappearance of both endocapillary cell proliferation and IgA
      deposition. It is known that methicillin-resistant S. aureus (MRSA) infection
      causes glomerulonephritis through T-cell stimulation by superantigen presented by
      MRSA. The present results suggest that not only MRSA but also MSSA can cause this
      type of glomerulonephritis.

PMID- 14586724
TI  - Longterm complete remission of AL-amyloid-related nephrotic syndrome.
AB  - We describe a 59-year-old man with nephrotic syndrome that was diagnosed as
      suspected minimal change nephrotic syndrome by the routine examination of renal
      tissues at first biopsy, because renal histology showed segmental mild mesangial
      expansion with argyrophilic staining and partial foot process fusion without any
      deposition. Prednisolone therapy induced complete remission of nephrotic
      syndrome. Relapse occurred after 4 years of complete remission, and the second
      renal biopsy revealed amyloid light-chain (AL)-amyloidosis. Re-examination of the
      first biopsy tissues by Congo red staining confirmed a small amount of amyloid
      deposition in the mesangial areas although the mesangial areas showed
      argyrophilic staining, which is atypical for amyloid deposition. This case raises
      a caution that even when renal histology is not suggestive of amyloidosis and
      prednisolone therapy is very effective, when a renal histology diagnosis is not
      confirmed, the clinician should suspect amyloidosis and should, at least,
      undertake Congo red staining to definitively rule out amyloidosis.

PMID- 14586725
TI  - Mesangial cell-predominant functional gene, megsin.
AB  - We obtained the "gene profile" of cultured human mesangial cells, and discovered
      five unknown genes predominantly expressed in mesangial cells. Megsin is one of
      these novel genes, and sequencing analysis of megsin showed that megsin belongs
      to the serpin (serine protease inhibitor) superfamily. The characteristics of
      megsin as a functional serpin are highly conserved among different species,
      including mice and rats. Expression of megsin is up-regulated in a variety of
      diseases with mesangial injury in humans and in animal models. We analyzed the
      promoter region of megsin and identified one positive regulatory motif, an
      incomplete activator protein-1 (AP-1) binding site within the region. Transgenic
      mice overexpressing megsin developed mesangial expansion and hypercellularity,
      which was associated with glomerular immune complex deposition. Our in vitro
      assays identified plasmin as a candidate target of megsin, although it is likely
      that megsin has other biological ligands in vivo. These results suggest that
      megsin plays an essential role in modulating the biological functions of
      mesangial cells. Megsin may play a role in the regulation of a wide variety of
      processes in mesangial cells, such as matrix metabolism, cell proliferation, and
      apoptosis. Identification of the exact biological functions and target proteases
      of megsin will lead us to develop novel therapeutic approaches to glomerular
      diseases.

PMID- 14586726
TI  - Clinical guidelines for immunoglobulin A (IgA) nephropathy in Japan, second
      version.
AB  - In 1995, clinical guidelines for the diagnosis and treatment of patients with
      immunoglobulin A (IgA) nephropathy in Japan were published by a joint committee
      of the Special Study Group on Progressive Glomerular Disease, Ministry of Health
      and Welfare of Japan (Chairman, Kiyoshi Kurokawa, MD), and the Japanese Society
      of Nephrology (President, Toshihiko Nagasawa, MD). The purpose of this new
      committee of the Special Study Group on Progressive Glomerular Disease, Ministry
      of Health and Welfare of Japan (Chairman, Hideto Sakai, MD), is to provide new
      clinical guidelines for the diagnosis and treatment of patients with IgA
      nephropathy in Japan. Although this document addresses current clinical practice
      in Japan, it is hoped that this English version will be helpful to the
      international community and will facilitate further discussion on this
      increasingly important disease.

PMID- 14586727
TI  - Inhibition of gluconeogenesis and p-aminohipuric acid accumulation in rat renal
      cortical slices by ionic and nonionic contrast media.
AB  - BACKGROUND: Renal dysfunction is a well-recognized complication induced by
      contrast media (CM). Nonionic CM have been introduced into clinical use to
      replace conventional ionic CM in an effort to reduce toxicity. However, the
      nephrotoxic effects of nonionic CM have not been fully evaluated. We previously
      determined the activities of N-acetyl-beta- d-glucosaminidase and gamma
      glutamyltransferase released from rat and human renal slices incubated with
      contrast media. Dose-dependent enzyme release from renal slices was observed, but
      there was no statistical difference in the increase of enzyme activities between
      ionic and nonionic CM. The present experiment was conducted to compare the
      effects of ionic and nonionic CM on the metabolic function of rat renal slices.
      METHODS: Rat renal cortical slices were incubated with ionic CM (diatrizoate,
      iothalamate) and nonionic CM (iopamidol, iohexol) at 37 degrees C for 90 min. To
      examine the dose-response effects of CM on gluconeogenesis and p-aminohipuric
      acid (PAH) accumulation in the rat renal slices, slices were incubated with 30,
      60, and 90 mg I/ml of CM. The inhibitory effects of nonionic CM on
      gluconeogenesis and PAH accumulation were compared with those of ionic CM in an
      independent experiment, in which slices were incubated with CM at a concentration
      of 60 mg I/ml. In addition, rat renal slices were incubated with mannitol instead
      of CM to investigate the effects of osmotic pressure on gluconeogenesis and PAH
      accumulation. RESULTS: A dose-dependent reduction of gluconeogenesis in rat renal
      slices was demonstrated by both ionic CM and nonionic CM. The inhibition of PAH
      accumulation was dose-dependent with nonionic CM, but not with ionic CM.
      Gluconeogenesis and PAH accumulation within the renal slices were both inhibited
      according to the increase in osmotic pressure produced by mannitol. The reduction
      in gluconeogenesis and PAH accumulation within the rat renal slices incubated
      with 60 mg I/ml of nonionic CM were significantly less than those resulting from
      the same concentration of ionic CM. CONCLUSIONS: Nonionic CM is less nephrotoxic
      than ionic CM with regard to gluconeogenesis and PAH accumulation in rat renal
      slices. These differences in nephrotoxic effect between ionic and nonionic CM may
      in part be attributable to differences in osmotic pressure.

PMID- 14586728
TI  - Resistance of CD28-deficient mice to autologous phase of anti-glomerular basement
      membrane glomerulonephritis.
AB  - BACKGROUND: The engagement of CD28 on T cells provides an essential costimulatory
      signal for T-cell activation and differentiation. Recent studies suggest that
      CTLA4Ig inhibits T-cell activation in vitro and in vivo, prevents acute and
      chronic allograft rejection, and induces tolerance in some experimental
      transplantation models. METHODS: The present study examined the role of the CD28
      costimulatory pathway in the induction of experimental anti-glomerular basement
      membrane (GBM) glomerulonephritis (GN). An accelerated type of anti-GBM GN was
      induced in wild-type mice and CD28-deficient (KO) mice. After 7 and 14 days,
      functional parameters, such as serum creatinine, amount of proteinuria, and serum
      mouse IgG levels were assessed. Histological studies were performed
      simultaneously to examine glomerular changes by light microscopy and
      immunoglobulin deposition by immunofluorescence staining. Flow cytometric
      analysis was undertaken to assess I-A(b) antigen expression on spleen cells.
      RESULTS: Anti-GBM GN induction was almost completely prevented in CD28-KO mice.
      CD28-KO mice had impaired ability to evoke B-cell activation, and developed lower
      mouse anti-rabbit IgG antibody titers in their serum than wild-type C57BL/6 mice.
      Furthermore, glomerular deposition of mouse anti-rabbit IgG was not detectable in
      CD28-KO mice after immunization with anti-GBM antibody. CONCLUSIONS: This is the
      first demonstration that the CD28 costimulatory pathway plays a critical role in
      autologous antibody production in anti-GBM GN, and suggests that effective
      inhibition of CD28-dependent autologous antibody production could be useful in
      the treatment of antibody-dependent GN in humans.

PMID- 14586729
TI  - Carbonic adsorbent AST-120 retards progression of renal failure by additive
      effect with ACEI and protein restriction diet.
AB  - BACKGROUND: In order to slow the progression of chronic renal failure (CRF), a
      multimodal approach should be applied if the efficacy is proved. Although
      compelling evidence of a beneficial effect exists for the use of angiotensin
      converting enzyme inhibitors (ACEIs) and low-protein diets, there is little
      evidence on whether carbon adsorbent has an effect on retardation of the
      progression of CRF. METHODS: In experiment 1, we examined whether the oral carbon
      adsorbent, AST-120, conferred an additive effect with captopril and an 80%
      restriction diet on the survival rate of 3/4 nephrectomized rats (3/4 NX). The
      3/4 NX rats were divided into three groups (C, control, n = 7; AD, captopril (an
      ACEI) +80% restriction diet (RD), n = 8; and ADK, ACEI + RD + AST-120, n = 8) and
      survival was observed for 72 weeks. In experiment 2, 3/4 NX rats were divided
      into four groups (C, control, n = 4; D, 80% restriction diet, n = 4; AD,
      temocapril + RD, n = 9; and ADK, temocapril + RD + AST-120, n = 9) for the
      examination of renal function, blood pressure, hematocrit (Ht), serum albumin,
      and proteinuria every month. We analyzed morphological changes in the kidney at
      48 weeks. RESULTS: In experiment 1, ADK did not improve the survival rate
      compared with AD, although ADK prolonged the survival significantly compared with
      C (C vs AD, P = 0.24; C vs ADK, P = 0.0007; AD vs ADK, P = 0.073). In experiment
      2, renal function and proteinuria were significantly ameliorated in the ADK group
      compared with AD at 48 weeks. Concomitantly with the preservation of renal
      function, pathological indices, including the glomerular sclerosis index and the
      interstitial fibrosis index, were significantly improved in ADK compared with AD.
      In the ADK group, Ht and serum albumin did not change over the 48 weeks.
      CONCLUSIONS: Administration of AST-120 in addition to an ACEI and a restriction
      diet preserves renal function independently of blood pressure control,
      angiotensin II inhibition, and protein restriction in 3/4 NX rats at 48 weeks,
      but does not improve the survival significantly.

PMID- 14586731
TI  - A new quantitative approach to the treatment of the dysnatremias.
AB  - Rapid correction of the dysnatremias can result in significant patient morbidity
      and mortality. To avoid overly rapid correction of the dysnatremias, the sodium
      deficit equation, water deficit equation, and Adrogue-Madias equation are
      frequently utilized to predict the change in plasma sodium concentration
      (Delta[Na+]p) following a therapeutic maneuver. However, there are significant
      limitations inherent in these equations. Specifically, the sodium deficit
      equation assumes that total body water (TBW) remains unchanged. Similarly, when
      using the Adrogue-Madias equation, the volume of infusate required to induce a
      given Delta[Na+]p is determined by dividing the target Delta[Na+]p by the result
      of this formula. This calculation also assumes that TBW remains constant. In
      addition, neither of these equations are applicable in the management of
      symptomatic syndrome of inappropriate antidiuretic hormone secretion (SIADH)
      because they fail to consider the subsequent increase in sodium excretion
      following the administration of infusate. Furthermore, in the treatment of
      hypernatremia, the water deficit equation is only applicable if the hypernatremia
      is caused by pure water loss. In hypernatremia caused by hypotonic fluid losses,
      the water deficit equation does not provide any information on the differential
      effect of infusates of variable [Na+] and [K+] on the [Na+]p. Finally, all these
      equations fail to consider any ongoing Na+, K+, or H2O losses. Taking all these
      limitations into consideration, we have derived two new equations which determine
      the volume of a given infusate required to induce a target Delta[Na+]p. These
      equations consider the mass balance of Na+, K+, and H2O, as well as therapy
      induced changes in TBW. The first equation is applicable to both hypernatremia
      and hyponatremia. The second equation is applicable to the management of severe
      symptomatic SIADH requiring intravenous therapy.

PMID- 14586730
TI  - Oral carbonaceous absorbent modifies renal function of renal ablation model
      without affecting plasma renin-angiotensin system or protein intake.
AB  - BACKGROUND: Although it has been repeatedly shown that the oral carbonaceous
      absorbent AST-120 ameliorates the progression of chronic renal failure, the
      mechanisms remain unknown. METHODS: Male Sprague-Dawley rats (6 weeks old),
      weighing 180-210 g, were 4/5 nephrectomized, and were divided into two groups:
      one given AST-120 (0.4 g/100 g body weight BW; n= 9) and the other not given AST
      120 ( n = 9). Body weight, blood pressure, and serum and urine chemistry, as well
      as the plasma components of the renin-angiotensin system, were measured for 22
      weeks. RESULTS: Proteinuria was significantly greater in the controls than in the
      AST-120 group (102 +/- 22 vs 51 +/- 7 mg/day at 22 weeks). Urea clearance was
      lower in the former (3.7 +/- 0.4 vs 3.9 +/- 0.4 ml/min). There were no
      differences in plasma renin activity (1.4 +/- 0.3 vs 1.9 +/- 0.4 mg/ml per h), or
      in angiotensin I (756 +/- 119 vs 1042 +/- 168 pg/ml) and II (35.1 +/- 7.4 vs 46.6
      +/- 7.6 pg/ml) or angiotensin-converting enzyme activity (39.0 +/- 2.4 vs 37.9 +/
      2.2 IU/l) between the two groups. Protein intake, estimated from urinary urea
      appearance, was not different. Serum phosphate concentration (6.6 +/- 0.3 vs 5.9
      +/- 0.3 mg/dl) was higher in the control than in AST-120, while the urinary
      phosphate excretion rate (31.5 +/- 0.8 vs 28.1 +/- 1.8 mg/day) tended to be lower
      in the latter. Conclusions. AST-120 retarded the progression of renal failure in
      the 4/5 renal ablation model without affecting the plasma renin-angiotensin
      system or protein intake, both of which were the most important risk factors for
      the progression of renal failure. We hypothesize that the renal protective
      effects of the oral absorbent AST-120 may be, at least in part, due to its
      lowering phosphate absorption from the diet as a phosphorus binder.

PMID- 14586732
TI  - A simple quantitative approach to analyzing the generation of the dysnatremias.
AB  - BACKGROUND: Although the dysnatremias are the most common electrolyte disorders
      in hospitalized patients, the complexity of the parameters normally used to
      explain their generation mechanistically is often bewildering to medical students
      and experts alike. A number of methods have been utilized clinically to analyze
      retrospectively and predict prospectively the pathogenesis of these disorders.
      These approaches include the measurements of plasma and urine osmolality, free
      water clearance, electrolyte free water clearance, and tonicity balance. METHODS:
      All previous analyses are problematic in that they fail to incorporate
      mathematically in a single equation the known factors that account quantitatively
      for changes in the plasma water sodium concentration. In this paper, we have
      derived a simple formula for use at the bedside based on all known factors that
      can generate the dysnatremias. The formula incorporates (1) the known empirical
      relationship between the plasma water Na+ concentration, total body water (TBW),
      and exchangeable Na+ (Na+(e)) and K+ (K+(e)); (2) changes in mass balance of H2O
      (VMB) and Na+ + K+ (EMB); and (3) the effect of hyperglycemia. RESULTS: This new
      equation, unlike all previous qualitative and quantitative approaches, can
      account mathematically for the simultaneous effects of TBW, Na(e), K(e), EMB,
      VMB, and the plasma glucose on the plasma water sodium concentration. Clinical
      examples are provided that demonstrate the utility of this new equation in
      analyzing the pathogenesis of the dysnatremias. CONCLUSION: The conceptual
      simplification resulting from the use of this formula should significantly
      improve the current approaches used in analyzing the generation of the
      dysnatremias.

PMID- 14586733
TI  - Circulating 1-84 PTH and large C-terminal PTH fragment levels in uremia.
AB  - BACKGROUND: The so-called "intact parathyroid hormone (iPTH)" assay detects large
      C-terminal PTH fragments that are lacking several N-terminal amino acid residues
      in addition to 1-84 PTH molecules. METHODS: Blood samples were obtained from 65
      predialysis patients (male, 35; female, 30) and 109 dialysis patients (male, 73;
      female, 36). The plasma 1-84 PTH levels were determined by a specific
      immunoradiometric assay (IRMA). RESULTS: The ratio of 1-84 PTH/iPTH did not show
      a significant correlation with glomerular filtration rate (GFR) among patients
      with a GFR of more than 80 ml/min, while it showed a positive correlation with
      GFR among patients with a GFR of less than 80 ml/min. The ratio of 1-84 PTH/iPTH
      demonstrated a significant tendency to decrease in the order of patients with
      normal renal function (0.928 +/- 0.182), those with renal dysfunction (0.836 +/-
      0.186; P < 0.05 vs patients with GFR > 80 ml/min [i.e., normal renal function]),
      and those with maintenance hemodialysis (0.618 +/- 0.123; P < 0.01 vs patients
      with GFR > 80 ml/min). The plasma levels of 1-84 PTH and conventional iPTH showed
      a close correlation in dialysis patients. Neither 1-84 PTH levels nor secondary
      parameters calculated from them showed a better correlation with bone metabolic
      markers than iPTH levels. CONCLUSIONS: Circulating large C-terminal PTH fragment
      levels are increased in uremic patients. However, this noninvasive study failed
      to demonstrate the superiority of the specific 1-84 assay compared with the
      conventional iPTH assay to evaluate bone metabolism.

PMID- 14586734
TI  - Multimeric vitronectin in ascites is involved in fibroblast spreading of EPS in
      patients on CAPD therapy.
AB  - BACKGROUND: Although encapsulating peritoneal sclerosis (EPS) is a serious
      complication of continuous ambulatory peritoneal dialysis (CAPD) therapy, the
      mechanism of the fibroneogenesis in EPS remains unknown. Because fibroblast
      adhesion and spreading to the extracellular matrix is the first step in
      peritoneal fibrosis, we investigated fibroblast spreading factor in ascites
      obtained from patients with EPS (EPS ascites). METHODS: To analyze fibroblast
      spreading activity, various concentrations of EPS ascites obtained from two EPS
      patients were coated on culture plates, and then the number of human fibroblasts
      (TIG-3) that had spread was counted. Each fraction of gel-filtered EPS ascites
      was also analyzed by this activity. Next, we examined the effect of the addition
      of Arg-Gly-Asp (RGD) peptides, several antibodies against adhesion molecules, and
      heparin on the fibroblast spreading activity in the EPS ascites. RESULTS: The
      fibroblast spreading activity of EPS ascites was about four times greater than
      that in ascites from a patient with nephrotic syndrome. Two major peaks (peak I
      and II) of spread cells were obtained when ascites were gel-filtered. The
      fibroblast spreading activities of the two peaks were abolished by the addition
      of RGD peptides and polyclonal antibody against vitronectin (VN). Immunoblotting
      analysis revealed that the two peaks contained VN and that peak I contained
      multimeric VN. Heparin, at 10 microg/ml, augmented the fibroblast spreading
      activity of peak I to about three times greater than the control. CONCLUSIONS:
      The results indicate that multimeric VN in EPS ascites plays a potential role in
      peritoneal fibrogenesis in EPS and that heparin may participate in peritoneal
      fibrosis in EPS.

PMID- 14586735
TI  - A patient with membranoproliferative glomerulonephritis diagnosed by the third
      biopsy via endocapillary proliferative glomerulonephritis and focal
      membranoproliferative glomerulonephritis.
AB  - We present a girl with type I membranoproliferative glomerulonephritis (MPGN)
      diagnosed by the third renal biopsy. The first renal biopsy was performed at age
      11.2 years after microscopic hematuria (which was revealed by school urinary
      screening) had persisted for 3 months, along with a low level of serum C3.
      Pathological examination of the biopsied specimen revealed endocapillary
      proliferative glomerulonephritis with multiple humps. The serum C3 level
      increased to within the normal range 2 months after the first renal biopsy, and
      the microscopic hematuria disappeared at age 12.3. However, microscopic
      hematuria, proteinuria, and the low serum complement level reappeared at age
      12.8. Pathological examination of a further renal biopsy that was performed at
      age 13.2 revealed focal MPGN with humps. Prednisolone therapy was subsequently
      initiated. Fluvastatin was added to her treatment regime when she developed
      hypercholesterolemia at age 13.6 and was continued even after normal cholesterol
      levels were reestablished. Pathological examination of the third renal biopsy,
      which was performed at age 15.2, revealed type I MPGN with humps. Serum C3
      normalized 6 months after the cessation of prednisolone at age 15.9. It is
      clinically important that patients with nontypical acute glomerulonephritis
      should be observed over a long period and repeated renal biopsies should be
      performed.

PMID- 14586736
TI  - Infection-associated hemophagocytic syndrome in a diabetic patient undergoing
      chronic hemodialysis.
AB  - Hemophagocytic syndrome (HPS) is an uncommon but severe illness associated with a
      variety of infections, malignant tumors, and autoimmune diseases. We report a
      case of infection-associated HPS in a patient receiving chronic hemodialysis.
      Peptostreptococcus-induced sepsis and abscess formation in the left iliopsoas
      muscle led to the onset of infection-associated HPS in this patient. The patient
      had diabetes mellitus and end-stage renal disease, and it is likely that
      immunological dysfunctions from these disorders played a part in the onset of
      both severe bacterial infections and HPS.

PMID- 14586737
TI  - Treatment of diabetic nephropathy with angiotensin II receptor antagonist.
AB  - Type 2 diabetes is an ever-growing problem worldwide. Approximately 40% of the
      patients with type 2 diabetes will develop diabetic kidney disease. In the United
      States, diabetes has become the most common single cause of endstage renal
      disease defined by the need for dialysis or transplantation. Patients with type 2
      diabetes and diabetic nephropathy have a dramatically increased cardiovascular
      risk. The Irbesartan Diabetic Nephropathy Trial was designed to determine whether
      the use of irbesartan or a calcium channel blocker would provide protection
      against the progression of nephropathy due to type 2 diabetes beyond that
      attributable to the lowering of blood pressure. In that study, 1715 hypertensive
      patients with nephropathy due to type 2 diabetes were randomly assigned to
      irbesartan 300 mg/day or amlodipine 10 mg/day, or placebo. All patients
      randomized in this trial had more than 900 mg of protein in their urine and serum
      creatinines between 1.0 mg/dl and 3.0 mg/dl. The target blood pressure was 135/85
      mmHg or less in all groups. The primary outcome was time to a combined endpoint
      of doubling of their baseline serum creatinine concentration, the development of
      endstage renal disease, or death from any cause. The mean duration of follow-up
      was 2.6 years. Treatment with irbesartan was associated with a risk of the
      primary composite endpoint that was 20% lower than that in the placebo group ( P
      = 0.02) and 23% lower than that in the amlodipine group ( P = 0.006). The risk of
      doubling of the serum creatinine concentration was 33% lower in the irbesartan
      group than in the placebo group ( P = 0.003) and 37% lower in the irbesartan
      group than in the amlodipine group ( P < 0.001). Treatment with irbesartan was
      associated with a relative risk of endstage renal disease that was 23% lower than
      that in both other groups. These differences were not accounted for by
      differences in the blood pressures that were achieved. Proteinuria was reduced on
      average by 33% in the irbesartan group as compared with 6% in the amlodipine
      group and 10% in the placebo group. The angiotensin II receptor blocker
      irbesartan was shown to be effective in protecting against the progression of
      nephropathy due to type 2 diabetes. In a study done in patients with type 2
      diabetes and early nephropathy as manifested by microalbuminuria, 590
      hypertensive patients with type 2 diabetes and microalbuminuria were randomized
      to receive either irbesartan 150 mg/day or irbesartan 300 mg/day and followed for
      2 years. The primary outcome in that trial was the time to the onset of diabetic
      nephropathy, defined by persistent albuminuria in overnight specimens, with a
      urinary albumin excretion rate that was more than 200 mg/min or at least 30%
      higher than the baseline level. The irbesartan 150 mg/day group demonstrated a
      39% relative risk reduction versus the control group in the development of overt
      proteinuria. The irbesartan 300 mg/day group demonstrated a highly significant
      70% risk reduction versus the control group ( P < 0.001). The albumin excretion
      rate was reduced in the two irbesartan groups throughout the study (-11% and -38%
      at 24 months compared with baseline in the irbesartan 150-mg and 300-mg groups,
      respectively). The albumin excretion rate remained unchanged in the control
      group. Irbesartan was demonstrated in the above study to be renoprotective,
      independent of its blood pressure-lowering effect, in patients with type 2
      diabetes and microalbuminuria. Thus, irbesartan, an angiotensin receptor blocker,
      was demonstrated to be significantly renoprotective in patients with type 2
      diabetes with either early nephropathy (microalbuminuria) or late nephropathy
      (proteinuria). The renoprotective effects of irbesartan were above and beyond the
      effects irbesartan had on systemic blood pressure. Patients with type 2 diabetes
      and either early or late diabetic nephropathy should be treated with the
      angiotensin II receptor blocker irbesartan.

PMID- 14586738
TI  - Molecular pathogenesis of nephrogenic diabetes insipidus.
AB  - There have been significant advances recently in the understanding of the
      molecular causes of nephrogenic diabetes insipidus. The resistance of the
      collecting duct to the action of vasopressin in this disorder results from
      abnormalities in several of the intricate steps that mediate the increase in
      principal cell hydraulic conductivity in response to the hormone. In this
      article, we review the current understanding of the known genetic causes of
      nephrogenic diabetes insipidus that affect the binding of vasopressin to the V2
      receptor and subsequent intracellular signaling events, as well as the
      translocation of aquaporin-2 water channels to the apical membrane. In addition,
      genetic diseases, which decrease collecting-duct water absorption by diminishing
      the interstitial medullary osmolarity, are discussed.

PMID- 14586739
TI  - Mitochondrial DNA deletion of proximal tubules is the result of itai-itai
      disease.
AB  - BACKGROUND: The pathogenesis of itai-itai disease continues to be controversial,
      although cadmium (Cd) poisoning which arises via polluted water and rice in Japan
      is likely involved. Until recently, however, a well-defined animal model for Cd
      intoxication was not available. An animal model for itai-itai disease was
      produced in rats by low-dose Cd treatment, intraperitoneally for a period of 70
      80 weeks. Osteomalacia followed the renal damage. RESULTS: A gene deletion in the
      mitochondrial DNA was found in the mitochondria of the proximal tubule cells of
      rats with chronic Cd intoxication, as was shown by the increased smaller PCR
      product seen by gel electrophoresis in one DNA region, where ATPase and
      cytochrome oxidase genes are located. However, the PCR product was different from
      that seen with a gene deletion associated with aging: del4834bp. Renal damage
      from Cd intoxication initially caused mitochondrial dysfunction indicated by the
      disturbance in reabsorption in the proximal tubules and decreased amounts of ATP,
      ATPase, and cytochrome oxidase with gradually progressing tubular proteinuria,
      and, finally, chronic renal failure with tubulointerstitial damage throughout the
      renal cortex. These gave rise to osteomalacia, subsequently. CONCLUSION: We
      concluded that in Cd poisoning, a mitochondrial gene deletion in the mitochondria
      of the proximal tubule cells was the primary event for the pathogenesis of
      osteomalacia in itai-itai disease.

PMID- 14586740
TI  - Suppression of experimental crescentic glomerulonephritis by peroxisome
      proliferator-activated receptor (PPAR)gamma activators.
AB  - BACKGROUND: It has been recently reported that peroxisome proliferator-activated
      receptors (PPARs)gamma exist in various tissues and that they exibit anti
      inflammatory effects. METHODS: We investigated the effects of PPARgamma
      activators on the development of crescentic glomerulonephritis. Crescentic
      glomerulonephritis was induced by the injection of rabbit anti-rat glomerular
      basement membrane antibody in WKY rats. RESULTS: Administration of troglitazone
      suppressed urinary protein excretion and crescent formation as indicated by
      crescent scores. Pioglitazone, a PPARgamma activator, mimicked the effect of
      troglitazone, but bezafibrate, a PPARalpha-activator, did not. Immunohistology
      revealed that troglitazone and pioglitazone inhibited the infiltration of ED-1
      positive monocyte/macrophages and CD8-positive cells into glomeruli. CONCLUSIONS:
      In the present study, we demonstrated that PPARgamma activators exert
      antinephritic effects by suppressing the recruitment of inflammatory cells via a
      PPARgamma-dependent mechanism.

PMID- 14586741
TI  - Roles of connective tissue growth factor and prostanoids in early streptozotocin
      induced diabetic rat kidney: the effect of aspirin treatment.
AB  - BACKGROUND: Connective tissue growth factor (CTGF) is a cysteine-rich growth
      factor induced by transforming growth factor-beta (TGF-beta) and is thought to
      play a critical role in TGF-beta-stimulated extracellular matrix accumulation. To
      explore its involvement in early diabetic nephropathy, we investigated the time
      course of CTGF gene expression and its regulation in streptozotocin (STZ)-induced
      diabetic rat kidney. METHODS: Northern blot analysis for CTGF, TGF-beta, and
      fibronectin expression was performed in the glomeruli of STZ-induced diabetic
      rats from 3 days to 12 weeks after the induction of diabetes, together with
      histological examination. To investigate the role of prostanoids in this process,
      aspirin was administered in one group of diabetic rats. Furthermore, CTGF
      expression was analyzed in rat mesangial cells cultured under high-glucose
      conditions. RESULTS: Glomerular expression of CTGF and TGF-beta1 mRNA was
      coordinately upregulated as early as day 3, followed by fibronectin induction and
      mesangial matrix accumulation. Chronic aspirin treatment in diabetic rats
      significantly attenuated mesangial expansion, and effectively suppressed CTGF
      induction, as well as inhibiting the upregulation of TGF-beta1 and fibronectin
      expression. In cultured mesangial cells, aspirin treatment abolished high glucose
      stimulated CTGF upregulation. CONCLUSIONS: These results indicate that CTGF
      expressed in the glomeruli is upregulated in the early stage of STZ-induced
      diabetic nephropathy in rats, and could be a critical mediator of the development
      of diabetic glomerulosclerosis. In addition, the modulatory effects of aspirin
      during this process suggest a role of the cyclooxygenase pathway in the
      progression of diabetic nephropathy.

PMID- 14586742
TI  - Mast cells and tubulointerstitial fibrosis in patients with ANCA-associated
      glomerulonephritis.
AB  - BACKGROUND: To elucidate the role of mast cells (MCs) in the pathogenesis of
      crescentic glomerulonephritis, we investigated the immunohistochemical
      localization of MCs in the kidney and the correlation between MC localization and
      tubulointerstitial lesions in biopsy specimens and serum stem cell factor (SCF)
      levels in patients with antineutrophil cytoplasmic autoantibody (ANCA)-associated
      glomerulonephritis. METHODS: Thirteen patients with ANCA-associated
      glomerulonephritis were enrolled in this study. Clinical parameters, such as
      serum creatinine and urinary protein excretion, were obtained from each patient
      at the time of biopsy. Paraffin-embedded sections were used for
      immunohistochemical staining, using the labelled streptavidin bio-tin (LSAB)
      method. Monoclonal antibodies to human tryptase, alpha-smooth-muscle actin, and
      CD68 were used as primary antibodies. Ten cortical interstitial fields were
      randomly selected at an original magnification of x400 and assessed using a
      computer-assisted color image analyzer. Tubulointerstitial fibrosis was assessed
      as the percentage of the area stained with Masson trichrome in ten cortical
      interstitial fields. The measurement of serum SCF levels was performed by using
      an enzyme-linked immunoassay. RESULTS: In all of the control subjects, a few
      tryptase-positive MCs were observed in the glomeruli and interstitium. In
      contrast, sparse MCs were observed in the interstitium, but not in the glomeruli
      of diseased kidneys. The number of interstitial MCs in the tubulointerstitial
      lesions was positively correlated with the degree of interstitial fibrosis.
      Moreover, a significant positive correlation was observed between the number of
      interstitial MCs and the serum SCF concentration (r = 0.85; P = 0.001).
      CONCLUSIONS: Our findings suggest that MC infiltration induced by SCF in
      interstitial tissues seems to be associated with tubulointerstitial fibrosis in
      human ANCA-associated glomerulonephritis.

PMID- 14586743
TI  - A comparison of corticosteroid and warfarin therapy in IgA nephropathy with
      crescent formation: preliminary trial.
AB  - BACKGROUND: No satisfactory treatment exists for IgA nephropathy (IgAN),
      especially in patients with severe histologic damage. Several trials using
      steroids combined with other therapies such as warfarin have demonstrated
      unremarkable results. We investigated the renoprotective effects of warfarin and
      steroids in IgAN patients with crescent formation. METHODS: Fifteen Japanese
      patients with IgAN were followed for up to 3 years. Crescent formation was
      recognized in over half of their glomeruli from renal biopsy specimens.
      Treatments consisted of either 0.5 mg/kg per day of prednisolone, or warfarin
      monotherapy. Blood pressure was controlled with long-acting calcium channel
      blockers and alpha-beta blockers. Serum creatinine and urinary protein excretion
      were evaluated at least every 2 months for 36 months. RESULTS: Ten of the 15
      patients completed the study. The serum creatinine levels had increased in both
      groups by 3 years, but significantly more so in the group treated with warfarin.
      However, they were not significantly different between the two groups as measured
      at the beginning and end of the study. Blood pressure for all patients in the
      study was maintained below 130/85 mmHg. Excluded from the study were 5 patients
      who experienced either peptic ulcers (n = 2, steroid group) or bleeding problems
      (n = 3, warfarin group). CONCLUSIONS: These results suggest that corticosteroid
      therapy may assist in preventing deterioration of renal function in patients with
      IgAN accompanied by crescent formation. However, further study would be required
      to decide its usefulness.

PMID- 14586744
TI  - Assessment of iron deficiency in chronic hemodialysis patients: investigation of
      cutoff values for reticulocyte hemoglobin content.
AB  - BACKGROUND: Recently, the usefulness of reticulocyte hemoglobin content (CHr) as
      a ferrokinetic marker in hemodialysis patients who receive recombinant human
      erythropoietin (rHuEPO) has been reported. However, a definite index for iron
      deficiency has not been established. In this study, a CHr cutoff value was
      investigated. METHODS: We retrospectively selected 27 hemodialysis patients by
      the following criteria: (1) hematocrit (Ht) values less than 30%, (2) patients
      receiving a stable dose of rHuEPO for at least 3 months, (3) patients who had not
      received iron supplements for at least 3 months, and had begun receiving iron
      supplements, (4) the doses of rHuEPO and iron supplements were unchanged for 8
      weeks following the start of iron administration. The iron supplement was
      administered at a dose of 40 mg/week, and Ht, CHr, transferrin saturation (TSAT),
      and serum ferritin were measured. The difference between the peak Ht value
      obtained at weeks 4-8 and Ht at baseline was calculated (DeltaHt). Patients with
      a DeltaHt of 3% or more were categorized as iron-deficient at baseline (group 1;
      n = 17). Patients with a DeltaHt of less than 3% were categorized as iron
      sufficient at baseline (group 2; n = 10). Each parameter was compared between the
      groups. RESULTS: Significant negative correlations between DeltaHt and CHr at
      baseline, and DeltaHt and TSAT at baseline were observed. CHr and TSAT were
      significantly lower in group 1 than in group 2 at baseline. CHr was less than 32
      pg in all patients in group 1, and greater than 32 pg in nine of the ten patients
      in group 2. If the CHr cutoff value was 32 pg, sensitivity was 100% and
      specificity was 90%. CONCLUSIONS: It is considered that 32 pg is appropriate for
      the CHr cutoff value.

PMID- 14586745
TI  - Long-term follow-up of type II membranoproliferative glomerulonephritis in two
      children.
AB  - We report the long-term follow-up of two patients with type II
      membranoproliferative glomerulonephritis (MPGN). One Patients was treated with
      high-dose alternate-day prednisolone and the other with dipyridamole. Both had
      favorable clinical courses over 8.5 and 15.5 years of follow-up, respectively.
      One patient who showed diffuse proliferative changes lost the urinary
      abnormalities 2 years after starting treatment. Her follow-up renal biopsies
      showed histological improvement. In the other patient, a boy, renal biopsy
      performed 6 years after the onset showed mild mesangial proliferation and a
      moderate matrix increase. His urine became normal 14 years after onset.
      Intramembranous electron-dense deposits persisted in these patients over 7 and 6
      years of observation, respectively. Patients with type II MPGN are usually
      difficult to treat and often progress to endstage renal failure. There is,
      however, a group of patients who have a favorable clinical course.

PMID- 14586746
TI  - Acute posterior leukoencephalopathy in a patient with nephrotic syndrome.
AB  - Reversible posterior leukoencephalopathy syndrome is one of the most serious
      complications of immunosuppressive therapy. The clinical features include
      headache, altered mental functioning, seizures, cortical blindness and other
      visual disturbances, with hypertension. The neuroimaging studies reveal
      predominant posterior leukoencephalopathy. Usually, antihypertensive therapy and
      reduction or withdrawal of immunosuppressive agents have been reported to resolve
      the neurological deficits and imaging abnormalities within a few weeks. We
      discuss here a 51-year-old woman with nephrotic syndrome who developed acute
      leukoencephalopathy during combination therapy with prednisolone and
      cyclosporine. She developed severe headache, visual disturbance, consciousness
      disturbance, and generalized tonic clonic convulsion. A computed tomography scan
      (CT) revealed low-density areas in the subcortices of the parietal and occipital
      lobes. Magnetic resonance imaging (MRI) disclosed a high signal intensity area on
      T2-weighted images and a low signal intensity area on T1-weighted images in the
      same lesions. Follow-up brain CT and MRI were performed several times. Three
      weeks after the first study, these lesions had completely resolved, but she had
      persistent altered consciousness for more than 1 year.

PMID- 14586747
TI  - Acute renal failure due to cholesterol crystal embolism treated with LDL
      apheresis followed by corticosteroid and candesartan.
AB  - Cholesterol crystal embolism (CCE) is caused by the shedding of cholesterol
      crystals into the bloodstream, and it has been recently recognized as a serious
      complication after vascular procedures. Our case of CCE, which was diagnosed by
      skin and renal biopsies, occurred in a patient with hypertension and diabetes
      mellitus, 3 months after coronary angiography, with the development of renal
      failure and blue toes. After low-density lipoprotein apheresis (LDL-A), the skin
      lesions, including livedo reticularis and pain from the acrocyanotic toes,
      dramatically improved, with partial recovery of renal function. Following the
      administration of low-dose corticosteroid and candesartan--an angiotensin II type
      1 receptor antagonist (ARB)--the eosinophilia disappeared and renal function
      improved gradually with a decrease in urinary protein excretion. Therefore, a
      combination therapy of LDL-A, low-dose corticosteroid, and an ARB is a possible
      treatment for CCE, although the possibility of spontaneous recovery of renal
      function cannot be eliminated for this patient.

PMID- 14586748
TI  - Unilateral renal cortical necrosis with contralateral hydronephrosis after
      surgery for uterus carcinoma.
AB  - Renal cortical necrosis (RCN) represents a rare cause of acute renal failure that
      is characterized by necrosis of the renal cortex with sparing of the medulla.
      Most previous RCN cases reported have been bilateral and have occurred in
      pregnancy. Unilateral RCN is a quite rare disorder. Here, we report a case of
      unilateral RCN with contralateral hydronephrosis after surgery for uterus
      carcinoma. In this patient it seems that hydronephrosis had been present before
      RCN occurrence. It is suggested that ureteric obstruction protects against RCN
      development.

PMID- 14586749
TI  - Adult staphylococcus scalded skin syndrome in a peritoneal dialysis patient.
AB  - Staphylococcal scalded skin syndrome (SSSS), a generalized exfoliative dermatitis
      complicating infections by exfoliative toxin-producing strains of Staphylococcus
      aureus, is rarely observed in adults, especially in those with chronic renal
      failure. In contrast to the mortality in infants, the mortality in adults is
      usually high. A case of generalized SSSS in a peritoneal dialysis patient is
      reported. A-62-year old Japanese man in whom peritoneal dialysis had been carried
      out was admitted to our hospital with acute peritonitis. It was intractable
      peritonitis in terms of resistance to various antibiotics; however, improvement
      of the peritonitis was shown after the injection of vancomycin. Nine days after
      the completion of this medication, erythema appeared in the eyes and mouth, and
      around the nostrils, with an exothermic reaction at 39.0 degrees C. Radial cracks
      formed in the face within a few days, and the erythema rapidly expanded to the
      neck, axilla, the whole body. The blood pressure was also lowered, and this led
      to a state of shock. Culture of skin biopsy specimens yielded identical strains
      of S. aureus. A presumptive diagnosis of SSSS was made. The patient was treated
      with antibiotics that were effective against the organisms and with both fluid
      supplementation and dopamine, resulting in subsidence of the signs and symptoms.
      The exothermic reaction and skin symptoms were improved promptly, with
      improvement in the general condition, including the state of shock. This appears
      to be the first reported case of SSSS caused by S. aureusin an adult patient with
      peritoneal dialysis who was treated successfully. It is very important that SSSS
      be differentiated from toxic epidermal necrosis, as the treatment is different.

PMID- 14586750
TI  - Cystic renal cell carcinoma, suspected because of lack of regression of renal
      cysts after renal transplantation in a dialysis patient with acquired renal
      cystic disease.
AB  - A 34-year-old man who had been on dialysis for about 6 years, and had acquired
      renal cystic disease, received a renal transplantation. However, in spite of the
      success of the transplantation, one area without cyst regression was observed in
      the original kidney. Therefore, carcinoma was suspected and nephrectomy was
      performed. Histology revealed cystic renal cell carcinoma (RCC). No case of
      cystic RCC occurring in a dialysis patient has previously been reported. Cystic
      RCC should be suspected in a cystic mass in the original kidney which does not
      regress after successful renal transplantation.

PMID- 14586751
TI  - Amlodipine-induced gynecomastia in two patients on long-term hemodialysis
      therapy.

PMID- 14586752
TI  - Forty years' experience in surgical treatment for esophageal cancer.

PMID- 14586753
TI  - Stereotactic radiosurgery (SRS) for multiple metastatic brain tumors: effects of
      the number of target tumors on exposure dose in normal brain tissues.
AB  - BACKGROUND: This study was carried out to clarify the practical limit of the
      number of stereotactic radiosurgery (SRS)-targeted tumors based on the
      irradiation dose of normal brain tissues. METHODS: Twenty-five patients with
      multiple brain metastases who received SRS from October 1998 to May 2002 were
      enrolled in the study. In each patient, the treatment options were thoroughly
      studied before deciding upon a course of treatment. The number of irradiated
      targets was increased one by one until all of the targets were included in a
      treatment plan. Given a surface dose of 25 Gy, we calculated the dose volume
      histogram (DVH) for the entire brain in each treatment plan and compared it with
      those of other treatment plans. Ultimately, only 5 of the 25 patients received
      irradiation for all of their tumors; the others received selective irradiation
      targeting only those tumors that were causing symptoms. RESULTS: When the number
      of targets increased, the DVH curve shifted to the right. The volume of the brain
      irradiated at a dose of 5 Gy or higher was 25.7% or less for 4 or fewer targets,
      45.7% for 5-6 targets, 81.0% for 7-8 targets and 100% for 9-11 targets. When the
      number of the targets exceeded 8, more than 50% of the entire brain was
      irradiated at levels of at least 8.7 Gy. The dose distribution became very
      complex as the number of targets increased. Although the survival time of the
      group in which tumors were selectively targeted was longer than that in the group
      in which all tumors were irradiated, the difference between the two groups was
      not statistically significant ( P = 0.2537). CONCLUSION: In SRS for multiple
      brain metastases, risks of both acute and late sequelae may increase because the
      exposure dose to normal brain tissues increases with increased numbers of target
      tumors. Dose distribution becomes more complex according to the increase in the
      number of targets. Based on our DVH curves, we conclude that the exposure dose to
      normal brain tissues is acceptable when the number of targets is less than 7.
      Importantly, our study also reveals that it may not be necessary or desirable to
      irradiate all metastatic tumors.

PMID- 14586754
TI  - Investigation of sentinel lymph nodes of the axillary and cubital regions in
      upper-extremity malignant skin tumors: a series of 15 patients.
AB  - BACKGROUND: Few articles have reported the location of sentinel lymph nodes
      (SLNs) in relation to skin-tumor location. We examined the location of SLNs in
      relation to skin-tumor location in the axillary and cubital regions. METHODS: We
      attempted to detect SLNs of the axillary and cubital regions using 1% sulfan blue
      dye in 15 patients with melanoma and other skin cancers. RESULTS: SLNs were
      detected in 12 patients: in 10 patients, one SLN was detected; in 2 patients, two
      SLNs were detected. In 4 patients, tumor metastasis in SLNs was positive. In 69
      samples, 16 metastatic lymph nodes were detected: tumor metastasis was recognized
      in 4 SLNs and in 12 other lymph nodes. In 8 patients, the SLNs were negative for
      tumor metastasis. Ten SLNs were found in 45 other samples; all lymph nodes were
      negative for tumor metastasis (false-negative rate, 0%). The SLNs were located in
      the following regions: central axillary nodes, 6 cases; lateral axillary nodes, 4
      cases; subscapular nodes, 1 case; cubital node, 2 cases. CONCLUSIONS: Because the
      lateral and central lymph nodes drain the lymph channels of the upper extremity,
      the SLNs were mainly located in the central and lateral lymph nodes in the
      axillary region. However, the ulnar dorsal hand tumors and the dorsal little
      finger skin tumors were connected to the cubital lymph node. It is necessary to
      check both the cubital and axillary regions when dyed lymph vessels are going
      toward the cubital region.

PMID- 14586755
TI  - A first feasibility study of temozolomide for Japanese patients with recurrent
      anaplastic astrocytoma and glioblastoma multiforme.
AB  - BACKGROUND: The efficacy of temozolomide has been evaluated in phase I and phase
      II trials in patients with recurrent malignant gliomas in the United States and
      the European Union. We report a feasibility study of the palliative efficacy of
      temozolomide for patients with recurrent anaplastic astrocytoma (AA) and
      glioblastoma multiforme (GBM). METHODS: Sixteen patients with at least two prior
      chemotherapy regimens were enrolled in the study. Nine patients were confirmed to
      have GBM and 7 patients were confirmed to have AA at the latest pathology review,
      and all had a Karnofsky performance status (KPS) of over 50%. The median age was
      57 years (range, 31-65 years). RESULTS: No cumulative toxicity was observed at
      any dose level when temozolomide was administered on a once-daily, 5-day
      schedule. Myelosuppression occurred, with the nadir being mid-late in the cycle
      (day 14 or 21). National Cancer Institute common toxicity criteria (NCI-CTC)
      grade 3 or 4 hematological toxicity did not occur. In the 9 GBM patients, the
      overall response rate (complete response + partial response [CR + PR]) was 0%.
      The median time to progression (TTP) was 3.5 months, and the rates of progression
      free survival (PFS) at 6 and 12 months were 40% and 0%. In the 7 AA patients, the
      overall response rate (CR + PR) was 29% and median TTP was 9 months, while PFS
      rates at 6 and 12 months were 80% and 30%. CONCLUSION: The favorable safety
      profile and the efficacy of temozolomide in Japanese patients are not
      incompatible with the results seen with patients in the United States and the
      European Union.

PMID- 14586756
TI  - Concurrent chemoradiotherapy for locally advanced and metastatic esophageal
      cancer: longterm results of a phase II study of UFT/CDDP with radiotherapy.
AB  - BACKGROUND: No effective treatment for advanced esophageal cancer extending to
      adjacent organs or associated with distant metastasis is known. We prospectively
      analyzed the efficacy of concurrent chemoradiotherapy with uracil plus tegafur
      (UFT) and cisplatin (CDDP) for such cases of advanced esophageal cancer. METHODS:
      Patients with advanced cancers received 60 to 70 Gy of radiotherapy given during
      a period of 7 weeks, concurrently with daily oral UFT (200 mg/m(2) per day), and
      a 24-h infusion of CDDP (70 mg/m(2)) on days 8 and 36. After chemoradiotherapy,
      UFT (250 mg/m(2)/per day) was administered daily for 1 year, while CDDP (80
      mg/m(2)) was administered twice every 4 weeks. RESULTS: Patients with stage III
      disease numbered 31, while 24 had stage IV disease according to the tumor-node
      metastasis (TNM) staging. Including all patients, complete response (CR) occurred
      in 20% and partial response (PR) in 51%. In stage III patients, CR, PR, and CR+PR
      rates were 29%, 48%, and 77%, respectively. In stage IV patients, CR, PR, and
      CR+PR rates were 8%, 54%, and 63%. Grade 4 leukocytopenia occurred in 22% of
      patients, and grade 3 pain, nausea/vomiting, and oral mucositis occurred in 7%,
      9%, and 4% of patients respectively, but resolved after the reduction or
      discontinuation of chemoradiotherapy. Median survival in stage III patients was
      415 days (range, 3 to 3046 days), and in stage IV patients, it was 187 days
      (range, 75 to 764 days). The 2-year survival rate in stage III patients was 25%
      and it was 4% in stage IV patients. The 5-year survival rate in stage III
      patients was 7%, while in stage IV patients it was 0%. CONCLUSION: This combined
      treatment may be a promising nonsurgical management option for locally advanced
      esophageal cancer, and can achieve good palliative effects in patients with
      distant metastasis.

PMID- 14586757
TI  - Laparoscopic radical prostatectomy: initial 30-case experience.
AB  - BACKGROUND: We carried out this study to clarify whether the operative methods of
      laparoscopic prostatectomy established in France could become standard therapy.
      The purpose was to evaluate the technical feasibility, oncological efficacy, and
      intraoperative and postoperative morbidity of laparoscopic prostatectomy
      performed by a general urologist. METHODS: Between June 2000 and August 2002, 30
      patients with clinically localized prostate cancer underwent laparoscopic radical
      prostatectomy performed as previously reported by Guillonneau and colleagues.
      Oncological data were assessed by pathological examination and by postoperative
      prostate-specific antigen (PSA) levels. All prostatectomy specimens were
      processed according to the Stanford protocol. Prostate features, including tumor
      weight; Gleason score; and the tumor status of the capsule, seminal vesicles, and
      surgical margins were studied. RESULTS: Complete laparoscopic removal of the
      prostate and seminal vesicles was achieved in all 30 patients. Operating time
      averaged 325.5 min (range, 165 to 880 min). The transfusion rate for the patients
      in the series was 50%, using own-blood transfusion (800-1200 ml). No patient
      required an allogenic blood transfusion. Only 2 of the 30 patients had a positive
      surgical margin that involved the urethra. There were three complications:
      bladder injury, rectal injury, and ileus associated with a drainage tube. No
      vascular, nervous system, or urethral complications were found. CONCLUSION: These
      preliminary results demonstrated that radical prostatectomy can be performed
      laparoscopically by general urologists. Laparoscopy offered better luminosity and
      magnification than conventional procedures, permitting precise dissection. Thus,
      laparoscopic prostatectomy could be a standard operation for patients with
      clinically organ-confirmed prostate cancer.

PMID- 14586758
TI  - Application of tyramide signal amplification for detection of N
      glycolylneuraminic acid in human hepatocellular carcinoma.
AB  - BACKGROUND: N-Acetylneuraminic acid and N-glycolylneuraminic acid (NeuGc) are the
      most common sialic acids in mammals, and NeuGc has attracted attention as a tumor
      associated antigen. METHODS: In frozen liver sections from patients with
      hepatocellular carcinoma, glycolipid-type NeuGc was detected on the surface of
      liver cancer cells in 9 of 17 samples (52.9%) by immunostaining, using two
      chicken monoclonal antibodies against NeuGc and the tyramide signal amplification
      method. When conventional immunostaining without amplification was used, all 17
      specimens tested were negative. RESULTS: Increased serum levels of anti-NeuGc IgG
      and/or IgM were observed in 13 of the 17 patients with hepatocellular carcinoma
      (76.5%). The presence of these antibodies was mostly attributed to the expression
      of NeuGc on hepatocellular carcinoma cells. Of the subjects with small HCCs
      (diameter 3 cm or less), 6 of 10 were positive for serum anti-NeuGc antibodies;
      however, 1 of these was negative for both serum Alpha-fetoprotein (AFP) and for
      prothrombin-induced vitamin K antagonist II (PIVKA-II). There was no correlation
      between serum AFP- or PIVKA-II, levels and the presence of NeuGc or anti-NeuGc
      IgG and/or IgM. CONCLUSION: The tyramide signal amplification method is useful
      for the immunohistochemical detection of low-level NeuGc expression by
      hepatocellular carcinoma cells. We therefore consider that measurement of serum
      levels of anti-NeuGc antibodies is clinically meaningful and that anti-NeuGc
      antibody may be a useful screening test, in combination with AFP and PIVKA-II,
      for the early diagnosis of hepatocellular carcinoma.

PMID- 14586759
TI  - Eradication and reinfection of human papillomavirus after photodynamic therapy
      for cervical intraepithelial neoplasia.
AB  - BACKGROUND: Photodynamic therapy (PDT) has been proven to be a promising
      therapeutic modality for selected dysplasias and malignancies in a variety of
      organs. We assessed the effectiveness of PDT for treating cervical
      intraepithelial neoplasia (CIN) by cytological and histological examinations and
      investigated its impact on human papillomavirus (HPV) infection. METHODS: A
      series of 31 patients with CIN (2 with CIN2, 29 with CIN3) were given
      polyhematoporphyrin ether/ester (PHE) 2 mg/kg IV. After 60 h their cervices were
      exposed to a 630-nm YAG-OPO laser. HPV-DNA extracted from cervical smears was
      amplified by the polymerase chain reaction and typed for HPV using restriction
      fragment length polymorphism. RESULTS: At 3 months after PDT, cytology and
      directed biopsy of the cervix revealed regression of the disease in 28 [complete
      remission (CR) rate 90%] of 31 patients, and HPV-DNA could be no longer detected
      in the cervical smears of 22 (76%) of 29 HPV-positive patients. After 12 months,
      all 31 patients had achieved a CR on biopsy, although HPV-DNA was still present
      in the cervical smears of 6 patients. The types of HPV-DNA detected 12 months
      after PDT were different from those seen before PDT in each of the 6 patients,
      suggesting that they might be reinfected with other HPV types after PDT.
      CONCLUSION: PDT is effective not only in improving the cytological and
      histological measures when treating CIN but also for eradicating cervical HPV.

PMID- 14586761
TI  - Rapid and aggressive recurrence accompanied by portal tumor thrombus after
      radiofrequency ablation for hepatocellular carcinoma.
AB  - Although radiofrequency ablation (RFA) has been reported to be a safe and
      effective procedure for the treatment of hepatocellular carcinoma (HCC), patterns
      of recurrence and complications following RFA treatment have not been fully
      identified. Recently, we have experienced two cases of HCC patients who developed
      rapid and aggressive recurrence accompanied by portal tumor thrombus after RFA
      therapy. The first was a 68-year-old woman with hepatitis C virus (HCV)-positive
      liver cirrhosis, who received percutaneous RFA therapy for a 27-mm-diameter HCC
      in segment VII. The other was a 64-year-old man with hepatitis B surface antigen
      (HBsAg)-positive liver cirrhosis and multiple bilobar HCCs, who underwent left
      hemihepatectomy and intraoperative RFA for the two tumors in the remnant liver.
      In both patients, though immediate imaging studies suggested complete necrosis of
      the tumors, recurrences with massive portal tumor thrombus occurred in 4 and 6
      months, respectively. At present, it is unclear whether such a recurrence pattern
      is directly related to the RFA procedure. However, it is implied that RFA therapy
      may entail a risk of promoting portal venous invasion of HCC tumors.

PMID- 14586760
TI  - C(H)OP refractory chronic lymphocytic leukemia patients in whom salvage
      chemotherapy chosen by evaluating multiple chemotherapeutic drug-resistant
      factors was remarkably effective.
AB  - It is well known that the expression of anticancer drug-resistant factors is
      elevated in patients with primary refractory or relapsed chronic lymphocytic
      leukemia (CLL) who have been treated with chemotherapy. We report here two C(H)OP
      refractory patients with CLL in whom salvage chemotherapy chosen by evaluating
      anticancer drug-resistant factors (glutathione-S-transferase-Pi [GST-Pi],
      glycoprotein [GP]-170, multidrug resistance-associated protein [MRP], and lung
      resistance protein [LRP]) was remarkably effective. A 71-year-old male patient
      was refractory to induction therapy with cyclophosphamide, vincristine, and
      prednisone (COP), and his leukemic cells at diagnosis displayed overexpression of
      GST-Pi and GP-170. A 74-year-old female patient's condition had been stable; she
      had received ten courses of COP over 9 years. However, because systemic
      lymphadenopathies recurred, she was treated with chemotherapy consisting of
      cyclophosphamide, adriamycin, vincristine, and prednisone (CHOP) or
      dexamethasone, etoposide, ifosphamide, and carboplatin (DeVIC). However, she did
      not respond at all, and her leukemic cells at recurrence displayed overexpression
      of GST-Pi. Therefore, we chose for these patients a salvage therapy consisting of
      dexamethasone and high-dose cytosine arabinoside (Ara C), to which neither GST-Pi
      nor GP-170 show any drug resistance. In both patients, this salvage therapy
      proved effective.

PMID- 14586762
TI  - Pelvic insufficiency fractures after preoperative radiotherapy for rectal
      carcinoma.
AB  - Insufficiency fractures of the pelvic bones are rare complications of
      radiotherapy, but they can cause significant morbidity. We report a patient who
      developed pelvic insufficiency fractures because of preoperative hypofractionated
      radiotherapy with chemotherapy for rectal carcinoma. She was treated with a four
      field box technique, receiving 20 Gy in four fractions, and she underwent
      concurrent pharmacokinetic modulating chemotherapy (PMC; intravenous infusion of
      5-fluorouracil [FU], 750 mg/body per 24 h and oral administration of uracil and
      futrafur [UFT] 400 mg/day) over a 1-week period. She developed severe buttock and
      femoral pain 10 months after this preoperative therapy. Physical examination at
      this time was unremarkable, with an absence of neurological signs, and
      radiographic examination was also normal, resulting in the patient initially
      being undiagnosed. However, 2 months after the onset of her initial pain, she was
      diagnosed as having pelvic insufficiency fractures on conventional radiographs.
      Although preoperative chemoradiotherapy has been widely accepted for improving
      local control and survival in patients with primary rectal carcinoma, surgeons
      need to be aware of this rare complication that can arise even 10 months after
      preoperative chemoradiotherapy.

PMID- 14586763
TI  - Longterm survival after surgical removal of solitary brain metastasis from
      osteosarcoma.
AB  - The prognosis of osteosarcoma with brain metastasis is very poor. We report a 14
      year-old girl with osteosarcoma of the right distal femur who is alive and free
      of disease 6 years after the craniotomy and irradiation for brain metastasis.
      This longterm survival is attributed to the absence of active pulmonary
      metastasis at the onset of brain metastasis and the complete removal of the brain
      metastasis by craniotomy. Patients without active pulmonary metastasis at the
      onset of brain metastasis may achieve longterm survival. In such patients, it
      would be worthwhile to perform craniotomy aggressively.

PMID- 14586767
TI  - Exocellular cyclic dipeptides from a Ruegeria strain associated with cell
      cultures of Suberites domuncula.
AB  - From cell cultures of Suberites domuncula was isolated a bacterial strain, SDC-1,
      which was identified by 16S ribosomal RNA sequence analysis as an alpha
      Proteobacterium of the genus Ruegeria. The occurrence of the strain in sponge
      cell culture could be explained by its resistance to the antibiotics used in the
      isolation of sponge cell cultures or by the preservation of SDC-1 by host sponge
      cells. The fatty acid composition of SDC-1 is characterized by branched C-12
      methyl fatty acids. Two new and 8 known cyclic dipeptides were isolated and
      characterized from the fermentation broth of SDC-1. Cyclodipeptides are one of
      the families of cell-cell signaling compounds and may have some role to play in
      sponge-bacteria interactions.

PMID- 14586768
TI  - Population structure and variation in red snapper (Lutjanus campechanus) from the
      Gulf of Mexico and Atlantic coast of Florida as determined from mitochondrial DNA
      control region sequence.
AB  - The mitochondrial DNA control regions of red snapper (Lutjanus campechanus) from
      the Gulf of Mexico (n = 140) and Atlantic coast of Florida (n = 35) were
      sequenced to generate a prestocking genetic baseline for planned stock
      enhancement. Intrasample haplotype and nucleotide diversities ranged from 0.94 to
      1.00 and 1.8% to 2.5%, respectively. All population analyses were consistent with
      the hypothesis that red snapper constitute a single, panmictic population over
      the sampled range. A ubiquitous, predominant haplotype, shared by 23% of the
      specimens, appeared to be evolutionarily recent, in contrast to previous findings
      based on restriction fragment length polymorphism data. Tajima's D values were
      suggestive of a recent bottleneck. Mismatch distributions from Gulf samples were
      smooth and unimodal, characteristic of recent population expansion. However, the
      Atlantic sample exhibited a comparatively broader, possibly multimodal
      distribution, suggestive of a more stable population history. Additional control
      region data may clarify potentially disparate demographic histories of Gulf and
      Atlantic snapper.

PMID- 14586769
TI  - Recent taxonomic changes and update of nomenclature for bacteria identified in
      clinical material.

PMID- 14586770
TI  - Glu528del in NEFL is a polymorphic variant rather than a disease-causing mutation
      for Charcot-Marie-Tooth disease in Japan.

PMID- 14586771
TI  - Identification of a novel liver-specific expressed gene, TCP10L, encoding a human
      leucine zipper protein with transcription inhibition activity.
AB  - The incidence of hepatoma is high in the Chinese population. Searching for genes
      involved in the functions of the liver, especially genes specifically expressed
      in the liver, will facilitate an insight into the molecular basis of normal and
      abnormal liver functions. Based on a differentially displayed cDNA fragment,
      which was down regulated in hepatoma tissues, we cloned a novel cDNA of 957 bp,
      TCP10L (T-complex protein 10 like), from the human liver cDNA library. Northern
      hybridization of this novel gene in 30 adult human tissues was examined. The
      result revealed that TCP10L expressed specifically in the human liver and testis.
      The TCP10L contains a 645-bp open reading frame encoding a deduced protein of 215
      amino acids. As the deduced protein was analyzed further, a typical leucine
      zipper motif was found. We firstly examined the transcriptional function of the
      TCP10L protein by transfecting recombinant pM-TCP10L into mammalian cells. The
      subsequent analysis based on the dual luciferase assay system showed that TCP10L
      significantly inhibited the expression of reporter genes. Compared with that of
      the negative control, the luciferase activity were down regulated in HEK293 and
      SK-HEP-1, CHO cells by about 2.6, 9.8, and 5.5 folds respectively. A mutated type
      of TCP10L was also constructed. It showed that the repression of TCP10L to the
      expression of the reporter gene almost completely decreased, suggesting that the
      leucine zipper structure is critical for TCP10L to play its role in regulation
      function. Then we transfected the recombinant TCP10L-EGFP into cells. The results
      indicated that TCP10L subcellularly located in nuclei, either in HEK 293 or SK
      HEP-1 cells. In addition, human TCP10L was found comprised of five exons and four
      introns, and mapped to chromosome 21q22.11.

PMID- 14586773
TI  - 2nd International Hernia Congress, London 19-21 June 2003.

PMID- 14586772
TI  - Characterization of six base pair deletion in the putative HNF1-binding site of
      human PXR promoter.
AB  - Pregnane X receptor (PXR) regulates transcription of drug metabolism genes such
      as CYP3A4 and MDR1. Several species of PXR transcripts have been reported,
      including hPAR-2 with an extended amino-terminus. Database search identified a 6
      bp deletion at the putative HNF1 binding element on the proximal region flanking
      to the hPAR-2 transcription start site. Aspirin-induced asthma (AIA) is a typical
      drug-induced phenotype due to aspirin or nonsteroidal antiinflammatory drugs, and
      these drugs are metabolized by CYP2C9 and UGT1A6, which are regulated by PXR. We
      examined a possible association between the 6-bp deletion variant and AIA; 129
      AIA patients and 117 controls were genotyped, and no allelic association was
      observed. Characterization of the hPAR-2 promoter revealed that the proximal
      region of 1.5-kb from the transcription start site conferred a promoter activity
      and that the 6-bp deletion diminished the activity. These results suggest that
      the putative HNF1 binding element is essential for the transcriptional activity
      of hPAR-2 and also, that substantial numbers of Japanese are in a deficient
      state. Because of the biological significance of the 6-bp deletion of PXR, the
      variant might potentially associate with as yet unknown phenotype.

PMID- 14586764
TI  - Presurgical evaluation and surgical treatment of medically refractory epilepsy.
AB  - Thanks to today's modern imaging examination techniques and especially to the
      common use of intracranial electrodes for localizing seizure foci, more and more
      patients with partial epilepsy can be treated microsurgically. The results of
      such neurosurgical therapies are very good, particularly in mesial temporal lobe
      epilepsy. In recent years, good results (60-70% seizure freedom) have also been
      achieved in extratemporal epilepsy surgery, so that such procedures can now be
      recommended for carefully selected patients. In this review, presurgical
      evaluations and the different surgical approaches are presented.

PMID- 14586774
TI  - Milestones in the history of hernia surgery: prosthetic repair.
AB  - Billroth (1878) envisaged prostheses before Bassini's sutured cure (1887). Phelps
      (1894) reinforced with silver coils. Metals were replaced by plastic (Aquaviva
      1944). Polypropylene (Usher 1962), resisting infection, became popular. Usher
      instituted tensionless, overlapping preperitoneal repair. Spermatic cord was
      parietalized, to obviate keyholing. Stoppa (1969) championed the sutureless
      Cheatle-Henry approach encasing the peritoneum. His technique, "La grande
      prosthese de renforcement du sac visceral" (GPRVS), was adopted by
      laparoscopists. Newman (1980) and Lichtenstein (1986) pioneered subaponeurotic
      positioning. Kelly (1898) inserted a plug into the femoral canal; Lichtenstein
      and Shore (1974) followed. Gilbert (1987) plugged the internal ring, and Robbins
      and Rutkow (1993) treated all groin herniae thus. Incisional herniation has been
      controlled by prefascial, retrorectus prosthetic placement (Rives-Flament 1973).
      ePTFE (Sher et al. 1980) is useful intraperitoneally, since it evokes few
      adhesions. Here, laparoscopy (Ger 1982) is competitive. Beginning in 1964
      (Wirtschafter and Bentley), experimental and clinical studies have shown
      herniation may be associated with aging and genetic or acquired (smoking, etc.)
      systemic disease of connective tissue. These data, with prospective trials, all
      but mandate tensionless prosthetic repair.

PMID- 14586775
TI  - Repair of large midline incisional hernias with polypropylene mesh: comparison of
      three operative techniques.
AB  - Polypropylene mesh is widely used for the reconstruction of incisional hernias
      that cannot be closed primarily. Several techniques have been advocated to
      implant the mesh. The objective of this study was to evaluate, retrospectively,
      early and late results of three different techniques, onlay, inlay, and underlay.
      The records of 53 consecutive patients with a large midline incisional hernia --
      25 women and 28 men, mean age 60.4 (range 28-94) -- were reviewed. Polypropylene
      mesh was implanted using the onlay technique in 13 patients, inlay in 23
      patients, and underlay in 17 patients. Either the greater omentum or a
      polyglactin mesh was interponated between the mesh and the viscera. The records
      of these 53 patients were reviewed with respect to: size and cause of the hernia,
      pre- and postoperative mortality and morbidity, with special attention to wound
      complications. Patients were invited to attend the outpatient clinic at least 12
      months after implantation of the mesh for physical examination of the abdominal
      wall. Postoperative complications occurred in 14 (26.4%) patients. The onlay
      technique had significantly more complications, as compared to both other
      techniques. Reherniation occurred in 15 (28.3%) patients. The reherniation rate
      of the inlay technique was significantly higher than after the underlay technique
      (44% vs 12%, P=0.03) and tended to be higher than the onlay technique (44% vs
      23%, P=0.22). Repair of large midline incisional hernias with the use of a
      polypropylene mesh carries a high risk of complications and has a high
      reherniation rate. The underlay technique seems to be the better technique.

PMID- 14586776
TI  - Classification of groin hernia: milestones.
AB  - Do we have true "milestones" along the hernia-classification route? I am not
      certain; modifications have been presented along the way, and each presentation
      (partially discussed herein) should be studied by every student of herniology and
      personal decisions made. In developing classifications, we should beware of too
      many hernia types. We must focus our attention and decisions upon each abdominal
      wall defect. These defects have been nicely described in readily available
      anatomic texts. Following this route, each surgeon may determine with ease and
      minimal complexity the appropriate approach and repair with confidence of cure.

PMID- 14586777
TI  - Elective neurectomy during open, "tension free" inguinal hernia repair.
AB  - Chronic postoperative inguinal pain syndromes are potentially debilitating
      sequelae following elective inguinal hernia repair. Diagnosis and definitive
      treatment constitute challenging issues for both the surgeon and the patient. In
      this prospective trial, we evaluated the impact of elective iliohypogastric and
      ilioinguinal nerve resection on the incidence of pain, numbness, and sensory loss
      following anterior, "tension-free" herniorrhaphy. One hundred ninety-one patients
      were enrolled and were reviewed 1 month, 6 months, and 1 year postoperatively.
      Pain, numbness, or any loss of sensation were recorded and categorized on a
      "mild," "moderate," or "severe" scale. No persistent pain syndrome was
      encountered. Numbness was found in 9.42% of the patients at the first month and
      in 6.28% of the patients after 1 year. Sensation loss (1.04%) was never
      bothersome or incapacitating at the end of the follow-up period. Elective
      neurectomy is safe to perform, well tolerated by patients, and is not associated
      with chronic postoperative inguinal pain.

PMID- 14586784
TI  - The rational use of oral care products in the elderly.
AB  - This review examines the evidence of the effectiveness of oral care products in
      preventing and controlling dental caries and periodontal disease in the ageing
      population. The strength of evidence is indicated using the following hierarchy:
      Type 1 (systematic reviews), Type 2 (randomised controlled trials), Type 3
      (observational studies) and Type 4 (traditional reviews). Most of the evidence to
      support the effectiveness of fluoride products is extrapolated from studies
      involving children and adolescents. The few studies that have been performed in
      older adults suggest that fluoride toothpaste and, in the case of high caries
      risk individuals, the adjunctive use of other fluoride delivery systems, may be
      effective in preventing coronal and root caries. Some dentifrices containing
      triclosan have been shown to improve plaque control and gingival health and one,
      which contains triclosan/copolymer, reduces the progression of periodontitis in
      adults and high-risk individuals. Powered toothbrushes with an oscillation
      rotation action are more effective in reducing plaque and improving gingival
      health than manual toothbrushes.

PMID- 14586785
TI  - Morphological characterization of the resin-dentin interface in primary teeth.
AB  - The effects of self-etching adhesives on primary teeth were evaluated. Reports in
      the literature suggest differences between the first and second dentition
      regarding the composition and the morphology and, therefore, a possible
      difference in the performance of dental adhesives. The purpose of this study was
      to evaluate the effects of self-etching adhesives on primary dentin. Eight dentin
      disks were obtained from the occlusal surface of primary molars. The disks were
      divided between four dental adhesives [Prompt L-PoP (LP), Clearfil SE BOND (SE),
      Etch&Prime 3.0 (EP) and Prime&Bond NT (PB) + H(3)PO(4) (Control) and "restored"
      with a composite (Pertac II)]. After sectioning, fixation and HMDS drying,
      specimens were polished and Field Emission SEM examinations were carried out.
      Clearly visible hybrid layer formation was found for PB, LP and EP. An
      undoubtedly detectable interdiffusion zone was not evident after the use of SE. A
      clearly visible adhesive layer was recognizable for PB, EP and SE, but not
      continuously detectable for LP. Debonded regions were observed for all systems
      evaluated, but distinct differences in the failure mode were detected. The
      evaluated dental adhesives did not generate completely sealed interfaces between
      the composite resin and the dentin of primary teeth in vitro.

PMID- 14586786
TI  - Enthalpy/entropy compensation phenomena in the reduction thermodynamics of
      electron transport metalloproteins.
AB  - Compensation phenomena between the enthalpy and entropy changes of the reduction
      reaction for all classes of electron transport metalloproteins, namely
      cytochromes, iron-sulfur, and blue copper proteins, are brought to light. This is
      the first comprehensive report on such effects for biological redox reactions.
      Following Grunwald's approach for the interpretation of H/ S compensation for
      solution reactions, it is concluded that reduction-induced solvent reorganization
      effects involving the hydration shell of the molecule dominate the reduction
      thermodynamics in these species, although they have no net effect on the E
      degrees values, owing to exact compensation. Thus the reduction potentials of
      these species are primarily determined by the selective enthalpic stabilization
      of one of the two oxidation states due to ligand binding interactions and
      electrostatics at the metal site and by the entropic effects of reduction-induced
      changes in protein flexibility.

PMID- 14586788
TI  - The function of nuclear receptors in bone tissues.

PMID- 14586787
TI  - Effect of temperature and guanidine hydrochloride on ferrocytochrome c at neutral
      pH.
AB  - Thermally denatured horse heart ferrocytochrome c (ferrocyt c) has been
      characterized using absorption spectroscopy, differential scanning calorimetry
      (DSC) and viscometry at pH 7.0. DSC experiments have yielded the transition
      temperature of denaturant-free ferrocyt c unfolding as 100.6+/-0.3 degrees C,
      indicating an extremely high stability of the protein. The presence of guanidine
      hydrochloride (GdnHCl) facilitated estimation of the structural features of
      thermally unfolded ferrocyt c. The stability of the protein, expressed by Delta
      G(D) at 25 degrees C, is 59+/-5 kJ mol(-1) (DSC) and 65+/-6 kJ mol(-1)
      (absorption spectroscopy). An absorption spectrum of ferrocyt c demonstrates that
      the heme occurs in the high-spin state at extreme denaturing conditions (94
      degrees C, 6.6 M GdnHCl). Absorption spectroscopy, using heme as a probe, shows
      that thermal denaturation of ferrocyt c occurs as a transition from a native low
      spin (Met80/His18) to a high-spin disordered state with involvement of non
      native, low-spin (bis-His) species.

PMID- 14586789
TI  - The mechanism of osteoclast differentiation from macrophages: possible roles of T
      lymphocytes in osteoclastogenesis.
AB  - Osteoclasts, which are present only in bone, are multinucleated giant cells with
      the capacity to resorb mineralized tissues. These osteoclasts are derived from
      hemopoietic progenitors of the monocyte-macrophage lineage. Osteoblasts are
      involved in osteoclastogenesis through a mechanism involving cell-to-cell contact
      with osteoclast progenitors. The recent discovery of osteoclast differentiation
      factor (ODF)/receptor activator of nuclear factor (NF)-KappaB ligand (RANKL)
      allowed elucidation of the precise mechanism by which osteoblasts regulate
      osteoclastic bone resorption. Synovial fibroblasts and activated T lymphocytes
      from patients with rheumatoid arthritis also express RANKL, which appears to
      trigger bone destruction in rheumatoid arthritis as well. Recent studies have
      shown that T lymphocytes produce cytokines other than RANKL, such as interleukin
      (IL)-17, granulocyte macrophage-colony stimulating factor (GM-CSF) and interferon
      (IFN)-Gamma, which have powerful regulatory effects on osteoclastogenesis. The
      possible roles of RANKL and other cytokines produced by T lymphocytes in
      osteoclast differentiation are described.

PMID- 14586790
TI  - Suppression of differentiation and proliferation of early chondrogenic cells by
      Notch.
AB  - Notch is a transmembrane protein involved in cell fate determination. In the
      present study, we observed temporally and spatially restricted expression of
      Notch1 in developing cartilage. Notch1 was localized starting from the
      mesenchymal condensation stage of embryonic mouse forelimbs. Interestingly,
      although localization could not be detected in the proliferating chondrocytes,
      obvious immunoreactivity indicating its expression was retained in the
      perichondrial region. Next, we investigated the expression of Notch1 and related
      molecules in a chondrogenic cell line, ATDC5 cells. Notch1, Delta-like (Dll)1,
      Deltex2, and Deltex3 were coexpressed after 6-day insulin treatment. Expression
      of Hairy and Enhancer of split homologue (HES)-1 followed thereafter. These
      results suggest that Notch may have a role in the early stage of chondrogenesis.
      To assess the effect of Notch activation, we cultured ATDC5 cells with a myeloma
      clone constitutively expressing Dll1, a ligand of Notch. We also used an
      adenovirus vector to express the constitutively active Notch1 intracellular
      domain (NIC). Activating either the endogenous or exogenous Notch receptor
      dramatically inhibited chondrogenic cell differentiation of ATDC5 cells, as
      assessed by Alcian blue staining of the cells and chondrocyte differentiation
      markers. Last, we investigated the effect of NIC on the proliferation of the
      ATDC5 cells. Expression of NIC by the adenovirus strongly suppressed thymidine
      incorporation. These results indicate that Notch is expressed in the initial
      stage of chondrogenic cell differentiation and has a strong inhibitory effect on
      both differentiation and proliferation of the cells when activated. The
      expression of Notch decreases as chondrogenic differentiation proceeds; however,
      a population of the cells with sustained expression of Notch1 become
      perichondrial cells. Considering that the perichondrium acts as a stem cell
      source of osteoblasts and chondrocytes, Notch1 may have a role in the formation
      of these cells by suppressing both differentiation and proliferation.

PMID- 14586791
TI  - Ultrastructural and cytobiological studies on possible interactions between PTHrP
      secreting tumor cells, stromal cells, and bone cells.
AB  - Parathyroid hormone-related peptide (PTHrP) induces pathological bone resorption
      in an endocrine manner, resulting in hypercalcemia of malignancy. However, the
      histopathological aspect of the action of PTHrP secreted by tumor cells on bone
      resorption has not well been documented. Therefore, we studied cell-cell
      interactions between bone cells, stromal cells, and PTHrP-secreting tumor cells
      (EC-GI-10) morphologically. Tumor cells injected subcutaneously into the parietal
      region formed a tumor mass, invading the bone marrow. The tumor mass was
      surrounded by a membrane structure consisting of stromal cells. These stromal
      cells were positive for alkaline phosphatase (ALPase). Tartrate-resistant acid
      phosphatase (TRAPase)-positive osteoclasts were localized close to the ALPase
      positive cells, and numerous osteoclasts were observed on the neighboring bone
      surfaces. PTHrP, vascular endothelial growth factor (VEGF), and matrix
      metalloproteinase (MMP)-9 were detected in the tumor cells. Using RT-PCR,
      expression of interleukin (IL)-1Alpha, IL-1Beta, and PTHrP, which are strong bone
      resorption factors, was detected in the tumor cells. Some ALPase-positive cells
      localizing on the neighboring bone surfaces and endothelial cells revealed
      PTH/PTHrP receptor immunoreactivity. Ultrastructurally, numerous blood vessels
      were observed between the tumor nests and the stromal cells. The nests were
      surrounded by a basement membrane, but it was discontinuous, therefore permitting
      direct contact between the tumor cells and the stromal cells. These results
      indicate that PTHrP secreted by tumor cells appears to stimulate osteoclast
      differentiation and bone resorption in a paracrine manner through PTH/PTHrP
      receptor-immunopositive cells. IL-1Alpha, IL-1Beta, VEGF, and MMP-9 may also be
      involved in facilitating osteoclast formation and the subsequent bone resorption.

PMID- 14586792
TI  - Osteoclast differentiation in ectopic bone formation induced by recombinant human
      bone morphogenetic protein 2 (rhBMP-2).
AB  - Osteoclast differentiation in the process of ectopic bone formation induced by
      recombinant human bone morphogenetic protein 2 (rhBMP-2) was examined to clarify
      the relationship between osteoclast development and rhBMP-2-induced bone
      formation. A combination of rhBMP-2 with a porous microsphere (PMS) and blood
      clot was implanted subcutaneously on the bilateral chest muscles of rats.
      Tartrate-resistant acid phosphatase (TRAPase) activity, cathepsin K (cath K), and
      calcitonin receptor (CTR), as markers of osteoclasts and their precursors, were
      examined using enzyme and immunohistochemical analysis up to 7 days after
      implantation. Mononuclear cells positive for TRAPase, cath K, and CTR first
      appeared on day 3 in connective tissue surrounding the PMS after implantation of
      rhBMP-2. Simultaneously, alkaline phosphatase activity became detectable in
      mesenchymal cells in the connective tissue. Electron microscopy demonstrated some
      mononuclear cells with abundant mitochondria and poorly developed rough
      endoplasmic reticulum in the proximity of mesenchymal cells. However, there was
      no evidence of cartilage or bone matrix formation on day 3. Osteoclasts in
      various stages of development, classified by the pattern of immunoreactivity for
      cath K, were observed by day 7. The polarized intracellular distribution of cath
      K was found only in osteoclasts attached to bone matrix. In conclusion, we have
      demonstrated for the first time the appearance of osteoclast precursors before
      bone matrix formation induced by rhBMP-2, suggesting that bone matrix is not a
      prerequisite for osteoclast precursor recruitment. Furthermore, we suggest that
      differentiation into polarized functional osteoclasts is accomplished when the
      osteoclasts attach to the bone matrix.

PMID- 14586793
TI  - Effects of an isopropanolic extract of Cimicifuga racemosa on urinary crosslinks
      and other parameters of bone quality in an ovariectomized rat model of
      osteoporosis.
AB  - A potential bone-sparing effect of Rhizoma actaeae (= cimicifugae) racemosae
      (black cohosh) was evaluated in ovariectomized Sprague-Dawley rats. The rats were
      ovariectomized at 12 weeks of age (body weight, 219-226 g) and placed on a soy
      free diet 6 days after surgery. Animals were randomly assigned the following
      groups: control (n = 10), soy-free diet only; RAL (n = 10), soy-free diet plus
      raloxifene 3 mg/kg intragastrically; and REM (n = 10), soy-free diet supplemented
      with an isopropanolic black cohosh extract (Remifemin) with a daily intake of
      4500 micro g triterpeneglycosides. Urinary levels of pyridinoline (PYR) and
      deoxypyridinoline (DPY), specific markers for bone loss, were measured at
      baseline and at weekly intervals. At the end of the study, the animals were
      killed and bone loss was determined by volumetric bone mineral density (BMD)
      measurements and peripheral quantitative computed tomography (pQCT). Mechanical
      resistance to fracture was also determined. Results demonstrated that an
      isopropanolic extract of black cohosh significantly diminished the urinary
      content of PYR and DPY and the morphometric correlates of bone loss associated
      with ovariectomy in rats. Reversal of the effects of ovariectomy on bone loss
      began 2-5 weeks after the start of treatment and continued through at least 7
      weeks. Results similar in quality and magnitude were obtained in the group
      treated with raloxifene, a known selective estrogen receptor modulator (SERM).
      Because extracts of black cohosh are already recognized as safe and effective in
      the treatment of certain gynecological disorders, a longer-term clinical trial of
      this herbal remedy for the treatment of osteoporosis is warranted.

PMID- 14586794
TI  - Lower bone cellular activities in male and female mature C3H/HeJ mice are
      associated with higher bone mass and different pyridinium crosslink profiles
      compared to C57BL/6J mice.
AB  - The female inbred strains of C3H/HeJ (C3H) and C57BL/6J mice (B6), having high
      and low femoral peak bone mass, respectively, were proposed as models for
      studying the genetic regulation of bone mass. Here, we compared the known bone
      phenotype, in 4.5-month-old C3H versus B6 mice, in both genders. Femoral bone
      mineral content, trabecular bone mass, and thickness at the distal metaphysis
      were higher in C3H mice. In the long bones, deoxypyridinoline content was lower
      and pyridinoline/deoxypyridinoline ratios were greater in C3H. Intrafibrillar
      collagen packing is different not only within strains but also within sexes. Bone
      resorption activity, evaluated by urinary pyridinium crosslinks and active
      resorption surfaces in the femoral metaphysis, was lower in C3H. Bone formation
      activity, evaluated by serum osteocalcin and alkaline phosphatase (ALP) levels,
      as well as histomorphometric indices of bone formation in the femoral metaphysis
      and the cortical tibia, was lower in C3H. Conversely, the ALP- and Von Kossa
      positive colony-forming units were more numerous in bone marrow cell cultures
      originating from male C3H. In both strains, resorption and formation activities
      were lower in males than in females. In C3H, males had lower bone mass than
      females whereas the opposite was seen in B6. In conclusion, we found that the
      lower cellular activities in C3H were associated with high cancellous bone mass
      and pyridinium crosslink levels, which might account for the more mineralized
      bone in C3H mice compared to that in B6 mice.

PMID- 14586795
TI  - Mandible bone loss in osteoporosis rats.
AB  - Change in the mandible during the development of osteoporosis has not been
      studied extensively. Thus, the present study was undertaken to clarify the target
      loci in the mandible during the development of experimental osteoporosis in aged
      female rats. Experimental osteoporosis was studied in 76 Wistar strain female
      rats, 35 weeks old, by means of ovariectomy and dietary calcium deficiency. The
      rats were divided into the following three groups: (1) group 1, unoperated basal
      control (Basal), maintained on a diet containing 1.0% calcium; (2) group 2, sham
      operated (Sham), maintained on a diet containing 0.01% calcium; and (3) group 3,
      ovariecomized (OVX), maintained on a diet containing 0.01% calcium. Fifteen rats
      of each group, except the basal rats (10 and 6 rats), were killed at 3 and 6
      months following ovariectomy, respectively. The mandible was extracted, cleaned,
      and then subjected to bone mineral content (BMC) and bone mineral density (BMD)
      analyses using a peripheral quantitative computed tomography (pQCT) bone scanner.
      Each mandible was scanned from the mesial margin of the first molar to distal
      margin of the second molar. The results showed that dietary calcium deficiency
      and ovariectomy caused significant decreases of trabecular and cortical BMCs and
      BMDs in Sham and OVX rats compared with Basal rats. Decreases due to dietary
      calcium deficiency were greater than those caused by ovariectomy. However,
      significant age-related changes were not observed in BMC and BMD in Sham and OVX
      rats for 3-6 months. In addition, the cortical and trabecular BMCs and BMDs
      obtained were found to relate to location in the mandible for each group.

PMID- 14586796
TI  - Classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency: a
      cross-sectional study of factors involved in bone mineral density.
AB  - Glucocorticoids are essential in the treatment of patients with congenital
      adrenal hyperplasia (CAH). The opposite actions of glucocorticoids and androgens
      in bone mass achievement justify a study of bone mineral density (BMD) in these
      patients. We evaluated BMD in patients with CAH due to classic 21-hydroxylase
      (CYP21A2) deficiency and investigated the involvement of clinical and laboratory
      factors in the BMD. This study assessed the clinical and laboratory factors
      involved in BMD of 45 patients at the Pediatric Unit of Endocrinology, UNICAMP,
      who had been diagnosed as having classical CAH due to CYP21A2 deficiency
      including molecular characterization. The sample consisted of 28 females and 17
      males; 23 salt-wasting (SW) and 22 simple virilizing (SV) cases, with average of
      9.9 years (ranges, 5.1-16.3 years) when bone densitometry was performed. The DEXA
      method was used for calculating the areal BMD Z score in L2-L4. The variables
      were analyzed with reference to the BMD for chronological age (BMD/CA), height
      age (BMD/HA), and bone age (BMD/BA). The mean Z score for BMD/CA was 0.08 +/-
      1.21 (-2.55 to 2.64); it was 0.29 +/- 1.33 (-2.01 to 4.00) for BMD/HA, and -0.90
      +/- 1.24 (-3.41 to 1.92) for BMD/BA. The BMD/CA was significantly lower in
      females and in patients on treatment for a long period and of more advanced
      chronological age. Weight and body mass index (BMI) Z scores showed a positive
      correlation with advanced BA. The higher the weight and BMI Z scores, the higher
      the BMD/HA. The BMD/BA values were significantly higher in the group in which BA
      was closer to CA. The BMD/BA value was significantly lower when compared to the
      value obtained with height and chronological ages. Sex, duration of treatment,
      weight, BMI, and bone age have an effect on areal BMD in patients with CAH due to
      CYP21A2 deficiency, which may be underestimated when evaluated in relation to CA
      and HA.

PMID- 14586797
TI  - Quantitative ultrasound of bone and clodronate effects in thalassemia-induced
      osteoporosis.
AB  - Osteoporosis in beta-thalassemia major has emerged as a topic of interest since
      optimized transfusion regimens have increased life expectancy and quality in
      these patients. Although the pathogenesis of thalassemic osteopathy is
      multifactorial, the evidence of an increased resorption phase suggests that the
      use of antiresorptive drugs such as bisphosphonates can be considered a valuable
      therapeutic strategy to reduce bone turnover and the risk of fragility fractures.
      We compared the effects of long-term cyclical clodronate therapy (300 mg
      intravenous infusion every 3 weeks for 2 years) and of an active placebo (calcium
      1 vitamin D) on bone mass and bone turnover in 30 male patients with beta
      thalassemia major. We also tested the possibility of using quantitative
      ultrasound (QUS) for assessing bone involvement in thalassemic osteopenia and in
      monitoring the response to antiresorptive therapy. Broadband ultrasound
      attenuation (BUA) was significantly reduced in patients with beta-thalassemia
      major as compared to healthy controls. In calcium and vitamin D-treated patients,
      a significant decline in spine, femoral, and total body areal bone density was
      observed. In the patients given intravenous clodronate we measured a substantial
      stability of bone mass, which was not significantly changed at the end of the
      study. The urinary excretion of deoxypyridinoline (a marker of bone resorption)
      showed a progressive significant decline throughout the study period in
      clodronate-treated patients. No significant change was observed in BUA values in
      both groups of patients. These results indicate that intermittent intravenous
      clodronate administration was not able to increase areal bone density in our
      thalassemic patients. Moreover, this is the first study to have assessed the
      usefulness of broadband ultrasound measurements in beta-thalassemia major.

PMID- 14586798
TI  - Factors influencing metacarpal bone mineral density in adults with cerebral
      palsy.
AB  - Several studies have examined bone mineral density (BMD) and related factors in
      children with cerebral palsy, but there are no such studies of adults with
      cerebral palsy. We evaluated BMD in 123 institutionalized adults (51 men aged 21
      41 years and 72 premenopausal women aged 24-46 years) with cerebral palsy, and
      examined the associations of BMD with mobility level, use of anticonvulsant
      drugs, and abnormal calcium metabolism status. Hand radiographs were used to
      measure BMD of the second metacarpal bone (mBMD). Body weight (kg), height (m),
      and body mass index (BMI) were recorded. Serum calcium, phosphate, and alkaline
      phosphatase were measured. Abnormal calcium metabolism, defined as calcium <8.5
      mg/dl, phosphate <2.6 mg/dl, or alkaline phosphatase >260 U/l, was identified in
      28% of the men and 31% of the women. Multiple regression analysis showed that the
      use of anticonvulsant drugs was significantly associated with lower mBMD in both
      sexes. Higher alkaline phosphatase level was significantly associated with lower
      mBMD in men. Mobility level (ambulation) was significantly associated with higher
      mBMD in women. Neither age nor BMI correlated with mBMD. Our findings indicated
      poor bone health status in adults with cerebral palsy and the existence of
      several factors that could affect bone metabolism in these patients.

PMID- 14586799
TI  - The relationship of sodium intake to calcium and sodium excretion and bone
      mineral density of the hip in postmenopausal African-American and Caucasian
      women.
AB  - During the past several decades in the United States, there has been a shift in
      dietary habits, with an increased consumption of processed foods that are high in
      sodium. It is known that calcium and sodium metabolism are linked and that higher
      sodium intakes may increase calcium excretion. Epidemiological studies in
      patients with idiopathic hypercalciuria suggest that hypercalciuria is linked to
      low bone mass. However, the relationship of sodium intake to bone mineral density
      (BMD) is controversial in Caucasians and has not been explored in African
      Americans. To determine the consequences of sodium intake on bone in African
      American and Caucasian postmenopausal women, sodium and calcium excretion and BMD
      of the total hip were measured in 50 Caucasian and 39 African-American
      postmenopausal women. After adjustment for race and urine volume, sodium
      excretion was a significant predictor of calcium excretion (P < 0.01). This
      relationship was modulated by calcium intake (P < 0.01), but not by race (P =
      0.63). There was no significant effect of sodium excretion (P = 0.42) or calcium
      excretion (P = 0.90) on BMD of the total hip after adjusting for race and urine
      volume. Sodium excretion is a significant predictor of calcium excretion in both
      postmenopausal African-American and Caucasian women. The relationship between
      sodium and calcium excretion is modulated by calcium intake, and the relationship
      is strongest at low calcium intakes (< or =1000 mg/day). However, sodium
      excretion in the range of 53.75-283.33 mmole/g/total volume (mmole/g/TV) is not a
      significant predictor of total hip BMD in elderly African-American and Caucasian
      postmenopausal women.

PMID- 14586800
TI  - Effect of alendronate on bone mineral density and bone turnover in Thai
      postmenopausal osteoporosis.
AB  - Alendronate has recently been approved for the prevention and treatment of
      postmenopausal osteoporosis, and its efficacy has been demonstrated in many
      Western countries. Our present study was performed to evaluate the effect of
      alendronate on bone mineral density (BMD) and its tolerability in Thais. Eighty
      postmenopausal women with osteoporosis participated in this study. After giving
      informed consent, the subjects were randomly allocated either 10 mg alendronate
      or placebo in a double-blind fashion. All patients received a supplement of 500
      mg elemental calcium daily. BMD at the lumbar spine, femoral neck, and distal
      forearm was measured at baseline and 6 and 12 months after treatment. Biochemical
      markers of bone resorption were determined at baseline and 6 months after
      treatment. Baseline characteristics were similar in both alendronate- and placebo
      treated groups. Ten subjects discontinued the study. Of 70 subjects, 32 received
      10 mg alendronate daily and the remaining subjects received placebo. At 1 year,
      BMD in the alendronate-treated group had increased from baseline by 9.2%, 4.6%,
      and 3.1% at lumbar spine, femoral neck, and distal forearm, respectively. These
      percentages were greater than those in controls (4.1%, 0.6%, and 1.0%,
      respectively). Urinary N-terminal telopeptide (NTx)-I and serum C-terminal
      telopeptide (CTx)-I levels decreased in both groups after 6 months of treatment.
      However, more reduction was demonstrated in the alendronate-treated group (71.9%
      vs. 28.4%, P < 0.01, and 84.7% vs. 33.1%, P < 0.01, respectively). Compliance
      with treatment and drug tolerability were good in both alendronate and placebo
      groups. We concluded that treatment with alendronate 10 mg daily for Thai
      postmenopausal women with osteoporosis significantly increased BMD at all
      skeletal sites and reduced biochemical markers of bone resorption. It was well
      tolerated without any serious side effects.

PMID- 14586801
TI  - Survey of gorillas (Gorilla gorilla gorilla) and chimpanzees (Pan troglodytes
      troglodytes) in Southwestern Cameroon.
AB  - A study on the distribution and population density of the western lowland gorilla
      (Gorilla g. gorilla) and the central chimpanzee (Pan t. troglodytes) was
      undertaken between December 1997 and August 2000 in the Campo and Ma'an Forests
      in southwestern Cameroon. The aim of this survey was to estimate the densities of
      the apes in different parts of the area, to assess the importance of the region
      for the conservation of these endangered species and to determine the influence
      of human activities such as logging and hunting. The survey was based on night
      nest counts on a total of 665.5 km of line transects. The overall density in the
      Campo Forest was estimated at 0.2 gorillas/km(2) and at 0.63-0.78
      chimpanzees/km(2). The overall density of chimpanzees in the Ma'an Forest was
      estimated at 0.8-1 individuals/km(2). Gorilla density in this area was too low to
      allow an estimation. The highest gorilla nest density was found in secondary
      forest. The gorilla density in unlogged forest was significantly lower.
      Chimpanzees showed a clear preference for less disturbed areas. In unlogged
      forest, old secondary forests (logging more than 23 years ago) and areas of
      recent logging with large remaining patches of primary forest, significantly
      higher densities were calculated than inside the more heavily exploited logging
      concession. In areas with both logging and high hunting pressure both species
      were rare or even absent. The Campo Ma'an area is considered a very important
      area for the conservation of gorillas and chimpanzees. Conservation measures are
      urgently required to reduce the impact of logging and hunting. The creation of
      the Campo Ma'an National Park in January 2000 is an important measure to preserve
      the unique biodiversity in this so far hardly protected area.

PMID- 14586802
TI  - Baby-transfer and other interactions between its mother and grandmother in a
      captive social group of lowland gorillas.
AB  - This report describes the responses of an experienced gorilla mother to
      inappropriate maternal behavior displayed by her young adult daughter toward a
      newborn baby and repeated acts of baby-transfer between these two females in a
      captive social group of lowland gorillas ( Gorilla g. gorilla). The quality of
      infant care by the young adult daughter clearly improved during the first 4 days
      after birth, and this improvement was at least partly based on her mother's
      encouragement. Thus, the mother's activities can be considered scaffolding for
      her daughter with regard to maternal infant care.

PMID- 14586803
TI  - Survey of black howler (Alouatta pigra) and spider (Ateles geoffroyi) monkeys in
      the Mayan sites of Calakmul and Yaxchilan, Mexico and Tikal, Guatemala.
AB  - Surveys of populations of spider and howler monkeys were conducted at the Mayan
      sites of Calakmul and Yaxchilan, Mexico and Tikal, Guatemala. The forests in
      which these sites are found are part of the largest landmass of tropical rain
      forests present in Mesoamerica, encompassing about 4 million ha. Triangulation of
      monkey vocalization combined with ground surveys was used to determine the
      presence of howler and spider monkey groups. Howler monkey mean troop size at
      these sites varied from 6.6+/-2.1 individuals in Yaxchilan to 7.5+/-1.9 in
      Calakmul to 8.7+/-2.2 in Tikal. Density estimates varied from 12.8
      individuals/km(2 )in Yaxchilan to 15.2 individuals/km(2 )in Calakmul to 17.8
      individuals/km(2 )in Tikal. Mean spider monkey subgroup size varied from 4.7+/
      2.6 individuals in Tikal to 5.6+/-3.0 individuals in Yaxchilan to 7.7+/-3.8
      individuals in Calakmul. Spider monkey density varied from 17.0 individuals/km(2
      )in Yaxchilan to 17.2 individuals/km(2 )in Calakmul to 56.4 individuals/km(2 )in
      Tikal. All sightings of both howler and spider monkeys at the three sites were in
      undisturbed rain forest vegetation and spider monkeys in general were more
      frequently sighted at higher tree heights than howlers. We discuss the value of
      further acquiring data on howler and spider monkey populations existing in
      extensive forest tracts and on the conservation value for both primate species of
      the forests surrounding the Mayan ruins found in this area of Mesoamerica.

PMID- 14586805
TI  - Bioluminescent bioreporter integrated-circuit sensing of microbial volatile
      organic compounds.
AB  - A bioluminescent bioreporter for the detection of the microbial volatile organic
      compound p-cymene was constructed as a model sensor for the detection of
      metabolic by-products indicative of microbial growth. The bioreporter, designated
      Pseudomonas putida UT93, contains a Vibrio fischeri luxCDABE gene fused to a p
      cymene/p-cumate-inducible promoter derived from the P. putida F1 cym operon.
      Exposure of strain UT93 to 0.02-850 ppm p-cymene produced self-generated
      bioluminescence in less than 1.5 h. Signals in response to specific volatile
      organic compounds (VOCs) such as m- and p-xylene and styrene, also occurred, but
      at two-fold lower bioluminescent levels. The bioreporter was interfaced with an
      integrated-circuit microluminometer to create a miniaturized hybrid sensor for
      remote monitoring of p-cymene signatures. This bioluminescent bioreporter
      integrated-circuit device was capable of detecting fungal presence within
      approximately 3.5 h of initial exposure to a culture of p-cymene-producing
      Penicillium roqueforti.

PMID- 14586806
TI  - Geographic occurrence of intermediate type between Castanopsis sieboldii and C.
      cuspidata (Fagaceae) based on the structure of leaf epidermis.
AB  - The number of layers of epidermis in the leaves is used as a criterion to
      distinguish between Castanopsis sieboldii (two layers) and C. cuspidata (one
      layer). An intermediate type, which has one and two layers within a single leaf,
      is frequently seen in the field. The origin of the intermediate type has been
      supposed to be a hybrid between C. sieboldii and C. cuspidata. If the
      intermediate type is produced by hybridization, we expect that the F(1) seedlings
      of the intermediate type should occur in the co-occurrence area of those two
      species. To clarify the geographic occurrence of the intermediate type, we
      collected nuts of 443 mother trees from throughout the distribution area of the
      genus Castanopsis in Japan. A total of 7,260 seedlings germinated from these nuts
      were examined as to their leaf structure. The seedlings of the intermediate type
      occurred not only in the area where C. sieboldii and C. cuspidata coexisted, but
      also in the area where only C. sieboldii grows. The leaf structure of
      intermediate seedlings was independent of the traits of mother trees. These
      findings suggest that the intermediate seedlings that occurred in the area where
      only C. sieboldii grows are not hybrid between C. sieboldii and C. cuspidata but
      are a morphological variation of C. sieboldii. The difference in the structure of
      leaf epidermis is not always appropriate for the identification of the hybrid.

PMID- 14586804
TI  - The oxygen transfer rate as key parameter for the characterization of Hansenula
      polymorpha screening cultures.
AB  - Screening cultures are usually non-monitored and non-controlled due to a lack of
      appropriate measuring techniques. A new device for online measurement of oxygen
      transfer rate (OTR) in shaking-flask cultures was used for monitoring the
      screening of Hansenula polymorpha. A shaking frequency of 300 rpm and a filling
      volume of 20 ml in 250-ml flasks ensured a sufficient oxygen transfer capacity of
      0.032 mol (l h)(-1) and thus a respiration not limited by oxygen. Medium buffered
      with 0.01 mol phosphate l(-1) (pH 6.0) resulted in pH-inhibited respiration,
      whereas buffering with 0.12 mol phosphate l(-1) (pH 4.1) resulted in respiration
      that was not inhibited by pH. The ammonium demand was balanced by establishing
      fixed relations between oxygen, ammonium, and glycerol consumption with 0.245+/
      0.015 mol ammonium per mol glycerol. Plate precultures with complex glucose
      medium reduced the specific growth rate coefficient to 0.18 h(-1) in subsequent
      cultures with minimal glycerol medium. The specific growth rate coefficient
      increased to 0.26 h(-1) when exponentially growing precultures with minimal
      glycerol medium were used for inoculation. Changes in biomass, glycerol,
      ammonium, and pH over time were simulated on the basis of oxygen consumption.

PMID- 14586808
TI  - Mechanobiology of soft skeletal tissue differentiation--a computational approach
      of a fiber-reinforced poroelastic model based on homogeneous and isotropic
      simplifications.
AB  - The material properties of multipotent mesenchymal tissue change dramatically
      during the differentiation process associated with skeletal regeneration. Using a
      mechanobiological tissue differentiation concept, and homogeneous and isotropic
      simplifications of a fiber-reinforced poroelastic model of soft skeletal tissues,
      we have developed a mathematical approach for describing time-dependent material
      property changes during the formation of cartilage, fibrocartilage, and fibrous
      tissue under various loading histories. In this approach, intermittently imposed
      fluid pressure and tensile strain regulate proteoglycan synthesis and collagen
      fibrillogenesis, assembly, cross-linking, and alignment to cause changes in
      tissue permeability (k), compressive aggregate modulus (H(A)), and tensile
      elastic modulus (E). In our isotropic model, k represents the permeability in the
      least permeable direction (perpendicular to the fibers) and E represents the
      tensile elastic modulus in the stiffest direction (parallel to the fibers).
      Cyclic fluid pressure causes an increase in proteoglycan synthesis, resulting in
      a decrease in k and increase in H(A) caused by the hydrophilic nature and large
      size of the aggregating proteoglycans. It further causes a slight increase in E
      owing to the stiffness added by newly synthesized type II collagen. Tensile
      strain increases the density, size, alignment, and cross-linking of collagen
      fibers thereby increasing E while also decreasing k as a result of an increased
      flow path length. The Poisson's ratio of the solid matrix, nu(s), is assumed to
      remain constant (near zero) for all soft tissues. Implementing a computer
      algorithm based on these concepts, we simulate progressive changes in material
      properties for differentiating tissues. Beginning with initial values of E=0.05
      MPa, H(A)=0 MPa, and k=1 x 10(-13) m(4)/Ns for multipotent mesenchymal tissue, we
      predict final values of E=11 MPa, H(A)=1 MPa, and k=4.8 x 10(-15) m(4)/Ns for
      articular cartilage, E=339 MPa, H(A)=1 MPa, and k=9.5 x 10(-16) m(4)/Ns for
      fibrocartilage, and E=1,000 MPa, H(A)=0 MPa, and k=7.5 x 10(-16) m(4)/Ns for
      fibrous tissue. These final values are consistent with the values reported by
      other investigators and the time-dependent acquisition of these values is
      consistent with current knowledge of the differentiation process.

PMID- 14586809
TI  - Computational study on the evolution of an intraventricular vortical flow during
      early diastole for the interpretation of color M-mode Doppler echocardiograms.
AB  - A computational fluid dynamics study of intraventricular flow during early
      diastole was carried out using a 3D model of the human left ventricle (LV). It
      was found that a vortical flow formed under the aortic orifice and then grew in
      size and extended laterally along the ventricular wall towards the posterior
      side. With further expansion of the LV, it developed into an annular vortex
      asymmetrically enlarged on the side of the aortic orifice, narrowing the passage
      of blood inflow and thus causing a shift of the high-velocity portion of inflow
      towards the apex. This appeared as an elongation of the aliasing area when the
      velocity of the inflow was expressed as a spatiotemporal map in the same manner
      as a color M-mode Doppler (CMD) echocardiogram. Based on these findings, it was
      concluded that the shape of the aliasing area in a CMD echocardiogram shows the
      change in the velocity of blood inflow affected by the development of an annular
      vortex formed in the LV.

PMID- 14586810
TI  - Directional dependence of osteoblastic calcium response to mechanical stimuli.
AB  - In adaptive bone remodeling, mechanical signals such as stress/strain caused by
      loading/deformation are believed to play important roles as regulators of the
      process in which osteoclastic resorption and osteoblastic formation are
      coordinated under a local mechanical environment. The mechanism by which cells
      sense and transduce mechanical signals to the intracellular biochemical signaling
      cascade is still unclear, however to address this issue, the present study
      investigated the characteristic response of a single osteoblastic cell, MC3T3-E1,
      to a well-defined mechanical stimulus and the involvement of the cytoskeletal
      actin fiber structure in the mechanotransduction pathway. First, by mechanically
      perturbing to a single cell using a microneedle, a change in the intracellular
      calcium ion concentration [Ca(2+)](i) was observed as a primal signaling response
      to a mechanical stimulus, and the threshold value of the perturbation as the
      mechanical stimulus was evaluated quantitatively. Second, to study directional
      dependence of the response to the mechanical stimulus, the effect of actin fiber
      orientation on the threshold value of the calcium response was investigated at
      various magnitudes and directions of the stimulus. It was found that the
      osteoblastic response to the perturbation exhibited a directional dependence.
      That is, the sensitivity of osteoblastic cells to a mechanical stimulus depends
      on the angle of the applied deformation with respect to the cytoskeletal actin
      fiber orientation. This finding is phenomenological evidence that cytoskeletal
      actin fiber structures are involved in the mechanotransduction mechanism, which
      may be related to cell polarization behaviors such as cellular alignment caused
      by mechanical stimulation.

PMID- 14586811
TI  - Examination of continuum and micro-structural properties of human vertebral
      cancellous bone using combined cellular solid models.
AB  - Two- and three-dimensional structural models of the vertebral body have been used
      to estimate the mechanical importance of parameters that are difficult to
      quantify experimentally such as lattice disorder, trabecular thickness,
      trabecular spacing, connectivity, and fabric. Many of the models that investigate
      structure-function relationships of the vertebral body focus only on the
      trabecular architecture and neglect solid-fluid interactions. We developed a
      cellular solid model composed of two idealized unit cell geometries to
      investigate the continuum and micro-structural properties of human vertebral
      cancellous bone in a mathematically tractable model. Using existing
      histomorphological data we developed structure-function relationships for the
      mechanical properties of the solid phase, estimated the micro-structural strains,
      and predicted the fluid flow characteristics. We found that the micro-structural
      strains may be 1.7 to 2.2 times higher than the continuum level strains between
      the ages of 40 and 80. In addition, the predicted permeability agrees well with
      the experimental data.

PMID- 14586812
TI  - A constrained mixture model for arterial adaptations to a sustained step change
      in blood flow.
AB  - A sustained change in blood flow results in an arterial adaptation that can be
      thought to consist of two general steps: an immediate vasoactive response that
      seeks to return the wall shear stress to its homeostatic value, and a long-term
      growth and remodeling process that seeks to restore the intramural stresses and,
      if needed, the wall shear stress toward their homeostatic values. Few papers
      present mathematical models of arterial growth and remodeling in general, and
      fewer yet address flow-induced changes. Of these, most prior models build upon
      the concept of "kinematic growth" proposed by Skalak in the early 1980s (Skalak R
      (1981) In: Proceedings of the IUTAM Symposium on finite elasticity. Martinus
      Nijhoff, The Hague, pp 347-355). Such approaches address important consequences
      of growth and remodeling, but not the fundamental means by which such changes
      occur. In this paper, therefore, we present a new approach for mathematically
      modeling arterial adaptations and, in particular, flow-induced alterations. The
      model is motivated by observations reported in the literature and is based on a
      locally homogenized, constrained mixture theory. Specifically, we develop a 3-D
      constitutive relation for stress in terms of the responses of the three primary
      load-bearing constituents and their time-varying mass fractions, with the latter
      accounting for the kinetics of the turnover of cells and extracellular matrix in
      changing, stressed configurations. Of particular importance is the concept that
      the natural configurations of the individual constituents can evolve separately
      and that this leads to changes in the overall material properties and empirically
      inferred residual stress field of the vessel. Potential applications are
      discussed, but there is a pressing need for new, theoretically motivated data to
      allow the prescription of specific functional forms of the requisite constitutive
      relations and the values of the associated material parameters.

PMID- 14586815
TI  - Average hydroxyapatite concentration is uniform in the extracollagenous
      ultrastructure of mineralized tissues: evidence at the 1-10-microm scale.
AB  - At the ultrastructural observation scale of fully mineralized tissues (l=1-10
      mum), transmission electron micrographs (TEM) reveal that hydroxyapatite (HA) is
      situated both within the fibrils and extrafibrillarly, and that the majority of
      HA lies outside the fibrils. The extrafibrillar amount of HA varies from tissue
      to tissue. By means of mathematical modeling, we here provide strong indications
      that there exists a physical quantity that is the same inside and outside the
      fibrils, for all different fully mineralized tissues. This quantity is the
      average mineral concentration in the non-collagenous space. This space is the sum
      of the extrafibrillar volume and of the volume of the fibrils that is not
      occupied by collagen molecules. Two independent sets of experimental observations
      covering a large range of tissue mass densities establish the relevance of our
      proposition: (i) mass density measurements and diffraction spacing measurements,
      re-analyzed through a dimensionally consistent packing model; (ii) optical
      density measurements of TEMs. The aforementioned average uniform HA-concentration
      in the extracollagenous space of the ultrastructure may emphasize the putative
      role played by a number of non-collagenous organic molecules in providing the
      chemical boundary conditions for mineralization of HA in the extracollagenous
      space. The probable existence of an average uniform extracollagenous HA
      concentration has far-reaching consequences for the mechanical behavior of
      mineralized tissues.

PMID- 14586817
TI  - [The stigmatisation of the psychiatrically sick is part of our culture].

PMID- 14586814
TI  - An ionised/non-ionised dual porosity model of intervertebral disc tissue.
AB  - The volume of the intrafibrillar water space--i.e. the water contained inside the
      collagen fibres--is a key parameter that is relevant to concepts of connective
      tissue structure and function. Confined compression and swelling experiments on
      annulus fibrosus samples are interpreted in terms of a dual porosity model that
      distinguishes between a non-ionised intrafibrillar porosity and an ionised
      extrafibrillar porosity. Both porosities intercommunicate and are saturated with
      a monovalent ionic solution, i.c. NaCl. The extrafibrillar fixed charge density
      of the samples is assessed using radiotracer techniques and the collagen content
      is evaluated by measurement of hydroxyproline concentration. The interpretation
      of the experimental data yields values for the intrafibrillar water content, the
      average activity coefficient of the ions, the Donnan osmotic coefficient, the
      fraction of intrafibrillar water, the stress-free deformation state, and an
      effective stress-strain relationship as a function of the radial position in the
      disc. A linear fit between the second Piola-Kirchhoff effective stress and Green
      Lagrange strain yielded an effective stiffness: H(e)=1.087 +/- 0.657 MPa. The
      average fraction of intrafibrillar water was 1.16 g/g collagen. The results were
      sensitive to changes in the activity and osmotic coefficients and the fraction of
      intrafibrillar water. The fixed charge density increased with distance from the
      outer edge of the annulus, whereas the hydroxyproline decreased.

PMID- 14586816
TI  - Contribution to the mechanics of worm-like motion systems and artificial muscles.
AB  - In this paper the author presents a mathematical model of a device that can be
      seen as a segment of an artificial worm (following the paradigm "earthworm") and
      as an artificial muscle as well. Confining considerations to statics, the model
      shows up as an ordinary parameter-dependent boundary value problem. It is tackled
      numerically in various particular forms by means of Maple and thus gives a good
      view of the segment's behavior during inflation and under longitudinal load.
      Segments of maximal volume present a useful preliminary stage of the
      investigations.

PMID- 14586818
TI  - [Stigmatizing concepts in vocational rehabilitation].

PMID- 14586819
TI  - [The stigma of mental illness from the patient's view--an overview].
AB  - QUESTION: This study provides an overview of the research on subjective
      stigmatization of mentally ill people. METHOD: All articles on this topic that
      have been published since the mid 1980 were analyzed. RESULTS: Mentally ill
      people are exposed to stigmatization in many ways. The anticipated and
      experienced stigmatizations as well as their attempts chosen for coping have
      fatal effects on their social relationships, their working situation, and their
      quality of life. The same is true for the emotional well-being and the self
      esteem of the ill. In addition, the fear of stigmatization has a negative effect
      on the help seeking behavior and the compliance of the ill with the psychiatric
      treatment. CONCLUSION: Efforts aimed at reducing stigmatization of mentally ill
      people should not be confined to fighting the discrimination objectively
      existing, but should also take into consideration the subjective stigma
      experiences of the persons affected.

PMID- 14586820
TI  - [The presentation of depression in German daily newspapers].
AB  - OBJECTIVE: According to results of the latest research, the state of knowledge of
      the German population regarding depressive disorders has improved during the last
      years. The question arises to what extent the print media have contributed to
      this development. METHOD: All editions of three German dailies--Sueddeutsche
      Zeitung (SZ), Frankfurter Allgemeine Zeitung (FAZ) and Bild Zeitung (BZ)-
      published in the first months of each quarter in 1990 and 2000 were analysed. All
      articles that were identified using the search key *depress* were included. A
      full text search was carried out, except for the editions of SZ and FAZ from the
      year 2000 which are available on CD-ROM. Using a coding system specifically
      designed for this study, a quantitative content analysis was carried out taking
      into consideration both formal and contents-related aspects. RESULTS: None of the
      three newspapers investigated helps to promote better understanding of depressive
      disorders. A comparison between 1990 and 2000 shows that there has been no
      development towards a more adequate representation of depression in any of the
      dailies examined. When aspects of the illness are mentioned it is mostly in the
      form of speculations over etiological factors. Rarely published articles that are
      rather confusing for lay people mostly report details taken out of their context.
      The term "depression" is often used metaphorically. Among the few descriptions of
      people with depression, negative aspects prevail. CONCLUSION: The image of
      depression as a serious mental illness can hardly be developed by reading the
      newspapers investigated. The improvement in lay people's state of knowledge
      cannot be attributed to a more adequate representation of depression in the daily
      newspapers examined.

PMID- 14586821
TI  - [The image of people with mental illness in movies: effects on beliefs, attitudes
      and social distance, considering as example the movie "The white noise"].
AB  - OBJECTIVE: To examine the impact of the movie "The White Noise" on the audience's
      beliefs and attitudes towards schizophrenia. METHOD: Survey with pre-post
      questionnaire to assess the knowledge about schizophrenia, stereotypical
      attitudes and social distance. RESULTS: Differences between the audience's
      knowledge about schizophrenia and expert opinion increased. Negative stereotypes
      reinforced and social distance increased. CONCLUSIONS: Treatment- and
      rehabilitation opportunities and coping with the illness in everyday life as well
      as the important role of support by family members and friends should be more
      accentuated to mediate more positive attitudes.

PMID- 14586822
TI  - [Expert's and lay attitudes towards restrictions on mentally ill people].
AB  - OBJECTIVE: Comparing experts' and lay opinions towards restrictions on mentally
      ill people. METHOD: We conducted a representative telephone survey with
      psychiatrists (N = 87) and lay persons (N = 90). RESULTS: Compulsory admission
      towards people with mental illness is the most accepted restriction (experts 98.9
      %/lay persons 72.2 %) followed by the withdrawal of the driver license (6.7
      %/54.1 %), abortion suggested for mentally ill women in case of pregnancy (5.6
      %/19.4 %), and the withdrawal of the right to vote (1.1 %/17.4 %). CONCLUSIONS:
      If assessing and carrying out restrictive measures towards people with mental
      illness, experts have to consider the discrepancy between their and the lay
      persons' opinions. Furthermore, professionals have to take an active role in the
      public discussion about sanctions that are not laid down in law by the law, e. g.
      abortion in case of pregnancy of a mentally ill woman, and that are not medically
      required. Thus, they contribute to the fight against the stigma that mentally ill
      people are faced with.

PMID- 14586823
TI  - [Increased stigma through a former stay in a mental hospital? Results of a public
      survey in Switzerland].
AB  - OBJECTIVE: The perception of how most people stigmatize mentally ill persons has
      consequences for the affected. Is a former stay in a mental hospital connected
      with an additional stigma? METHOD: In three linguistic areas of Switzerland we
      conducted a representative opinion survey (N = 1737) on public attitude towards
      mental illness, psychiatric treatment, and the institutions involved. Using
      Link's "devaluation-discrimination-scale" a randomly selected sample was asked on
      the telephone about the perceived stigma concerning (1) a currently mentally ill
      person or (2) a former mentally ill person or (3) a former mental inpatient.
      RESULTS: In all three linguistic areas of Switzerland we found in the case of
      current illness a lower social acceptance or a higher discrimination,
      respectively. Also in all linguistic areas those who were asked about "former
      mental illness" or "former stay in a mental hospital" did not differ regarding
      perceived acceptance or discrimination. DISCUSSION: Our data does not confirm the
      assumption of increased stigma because of a former stay in a mental hospital. An
      inquiry of subjective experience of a hospital stay, however, would probably lead
      to other results than that of a public survey.

PMID- 14586824
TI  - [From the person to an isolated case: Frank Schmokel in the discourses of power
      and stigmatization].
AB  - OBJECTIVE: Representations of psychiatry in the media reflect the societal
      perception of psychiatries. These representations are influential in terms of
      society and health politics in that the societal perception of psychiatry is
      determined by the media, and the media convey what is thinkable and sayable.
      METHOD: A formal textual analysis, employing a discoursive analytical method (M.
      Foucault), will be carried out based on the concrete example of the daily
      coverage of the case of Frank Schmokel. RESULTS: It will be demonstrated that the
      means by which the media sketched an image of Frank Schmokel left little
      understanding for the person and his action. Schmokel was exposed to a sphere of
      control which arose from various competing discourses. The crystallization of the
      participating discourses (psychiatry, law, publicity) in power shows, in addition
      to repeated stigmatization and the generation of cliches, the isolation of the
      individual: the person Frank Schmokel is made into an isolated case. CONCLUSIONS:
      Images of this type are quickly generalized and lead to a public image of
      psychiatry (psychiatries) that distort reality. Such conveyance of opinion is
      amazingly influential in terms of societal politics and health politics, and has
      repercussions in law and politics.

PMID- 14586825
TI  - [Stigma as perceived by schizophrenics and depressives].
AB  - QUESTION: The goal of this study is to investigate the stigma of mental illness
      from the perspective of the persons directly affected by it. METHOD: 210 patients
      with schizophrenia or major depression were questioned about anticipated and
      concrete stigmatization experiences, using a questionnaire especially developed
      for this study. RESULTS: Most of the patients expected negative reactions from
      the environment. Three quarters were convinced that their job application would
      be rejected when it became known that they are mentally ill. Almost two thirds
      felt apprehensive that others would avoid them due to their illness. There is
      hardly any difference between schizophrenia and depressive patients' assessment
      of stigmatization of mentally ill people. Concrete stigmatization experiences
      were most frequently reported in the domain of interpersonal interaction. Second
      comes the distorted picture of mentally ill people that is depicted in the media
      and experienced as hurtful by the patients. The obstacles to access social roles
      (partnership, work, etc.) perceived by the patients come third. Participants
      least frequently mentioned structural discrimination, i. e. disadvantages
      regarding psychiatric treatment or rehabilitation measures. Contrary to
      anticipated stigmatization, there are differences between the two diagnostic
      groups when it comes to concrete stigmatization experiences. Schizophrenia
      patients more frequently report that others would avoid contact with them and
      that the access to social roles was especially complicated for them. They also
      seemed to be more exposed to structural discrimination than depressive patients.
      CONCLUSION: Based on the results of this study, ways are discussed of how
      stigmatization and discrimination of mentally ill people can be reduced.

PMID- 14586826
TI  - ["Anti-stigma campaign from below" at schools--experience of the initiative "Irre
      menschlich Hamburg e.V."].
AB  - In the process of stigmatisation psychiatry is not neutral but it is up-to-date
      as well as historically involved. That is why it is responsible to influence not
      only the social perception of psychiatry but also the public picture of mentally
      disturbed people in a positive way. Doing so it is dependent on the help of
      psychosis-experienced persons and relatives. Only working together a plausible
      enlightenment, that points beyond the status quo, can be achieved. Anti-stigma
      work must critically reflect the interactions in psychiatry itself. After an
      analysis of the different concepts of stigmatisation and anti-stigma work there
      follows the evaluation of an information campaign at schools in Hamburg, which
      emerged from the Hamburg psychosis seminar. The personal meeting of students and
      psychosis experienced persons is of immediate importance. In addition to that
      media about the subject "being different, madness, mental disturbation" are being
      placed at the teachers disposal according to their wishes. In the meantime
      experience is there of more then 50 teaching units in primary advanced and
      secondary education as well as of a special open day attended by over 500
      students. The response of students and teachers is definitely positive. For the
      psychosis experienced persons involved there is a special benefit in the sense of
      empowerment. The more health politically based motives of the anti-stigma work
      have meanwhile been completed by educational justifications. This way of open
      meeting is also being discussed as a completion to the symptom based early
      diagnosis.

PMID- 14586828
TI  - Surgical pathology for the oncology patient in the age of standardization: of
      margins, micrometastasis, and molecular markers.
AB  - From initial diagnosis through definitive treatment, pathologic evaluation plays
      a central role in the care of patients with cancer. All patient management is
      dependent on the correct tissue diagnosis. For surgically resected malignancies,
      the pathologic stage is widely recognized as the most accurate predictor of
      survival, and it typically determines the appropriateness of adjuvant treatment
      as well. Numerous additional pathologic factors have been shown by multivariate
      analyses to have prognostic significance that is independent of stage, and these
      may help to further substratify tumors, individualize treatment, and more
      accurately predict outcome. On a larger scale, pathologic data are essential for
      epidemiologic and clinical research and is the common language of cancer
      worldwide. Despite its overriding importance, however, current pathologic
      analysis is fraught with variations in methodology, interpretation of findings,
      terminology, reporting norms, and statistical approaches that compromise its
      utility, both to the individual patient and to the progress of cancer medicine
      and research. In the last 5 years, increasing attention has been focused on the
      negative impact of variation in pathology practices on patient care and medical
      progress at all levels including institutional, regional, national, and
      international. This problem is within the immediate ability of the pathology
      profession to correct, and the author's prediction for oncologic pathology over
      the next 5 years is that standardization based on best practices will become,
      itself, the standard.

PMID- 14586829
TI  - Imaging of rectal cancer.
AB  - Radiologic evaluation of rectal cancer is invaluable in aiding the surgeon,
      gastroenterologist, and oncologist in the initial and follow-up management of
      patients with this malignancy. This review highlights recent developments in
      computed tomography; ultrasonographic, metabolic, and magnetic resonance imaging
      of rectal cancer; its clinical ramifications; and the direction of future
      efforts.

PMID- 14586830
TI  - Controversies in the surgical management of rectal cancer.
AB  - At the present time, standard therapy for potentially curable rectal cancer
      consists of transabdominal surgical resection and adjuvant chemoradiation for
      American Joint Committee on Cancer stage II/III disease. Controversial issues
      include the use of local excision as opposed to formal resection and total
      mesorectal excision (TME) alone without adjuvant therapy. Although early stage
      tumors are the ideal potential candidates for local excision, clinical staging
      with endoscopic ultrasound is extremely variable in accurately predicting T and N
      stage. In addition, even low-grade or T1 tumors are associated with a 7% to 14%
      chance of nodal metastatic disease. Overall, the risk for local recurrence is
      higher after local excision but may be reduced by adjuvant therapy. Salvage rates
      for recurrent disease range from 21% to 91%. In regard to TME, local recurrence
      rates are an impressive 0% to 12% without adjuvant radiation. However, the
      addition of radiation therapy may further reduce these already low rates,
      especially in higher-risk groups. The results of 2 large European studies show
      acceptable complication rates and the applicability of this technique to a
      diverse patient population.

PMID- 14586831
TI  - Rectal cancer: Preoperative versus postoperative irradiation as a component of
      adjuvant treatment.
AB  - The search for improved disease control and survival for resectable but high-risk
      rectal cancers has led to studies that combine all 3 modalities. For surgically
      resected, high-risk rectal cancers, postoperative chemoradiation has been shown
      to improve both disease control (local and distant) and survival (disease free
      and overall) and was recommended as standard adjuvant treatment at the 1990
      National Institute of Health Colorectal Cancer Consensus Conference. Three
      randomized studies showed improved overall survival (OS) and local control for
      patients treated with postoperative irradiation and chemotherapy when compared
      with surgery alone or surgery plus irradiation control arms. These include 2 US
      trials, Gastrointestinal Tumor Study Group and Mayo/North Central Cancer
      Treatment Group (NCCTG) and a Norway trial. Although most preoperative external
      beam radiation trials show reductions in local relapse with the addition of
      preoperative EBRT to resection, only the large Swedish trial of approximately
      1,100 patients showed a survival improvement when compared with a surgery alone
      control arm for resectable primary rectal cancers. In a recent pooled analysis of
      3 postoperative adjuvant rectal cancer trials (NCCTG 794751, NCCTG 864751, and GI
      Intergroup 0114) survival and disease relapse were dependent on both TN and NT
      stage of disease (N substage within T stage and T substage within N stage). Even
      among N2 patients (4 or more positive nodes), T substage influenced 5-year OS (T1
      2, 69%; T3, 48%; and T4, 38%; P <.001). Ongoing randomized trials are being
      conducted for patients with high-risk, resectable primary rectal cancers. The
      intent is to help define optimal combinations of postoperative chemoradiation (US
      GI Intergroup), to test sequencing issues of preoperative versus postoperative
      chemoradiation (Germany trial), and to determine if concurrent and maintenance 5
      FU and leucovorin add to the benefits found with preoperative irradiation
      (European Organization for Research and Treatment of Cancer). For subsequent
      trials, it may be preferable to perform separate studies, or a planned
      statistical analysis, for different risk groups of patients (low, intermediate,
      moderately high, and high), as defined in the rectal cancer pooled analysis.

PMID- 14586832
TI  - Technical aspects of image-based treatment planning of rectal carcinoma.
AB  - The role of 3-dimensional treatment planning in the management of rectal cancer
      is not well defined. This report reviews technical guidelines for simulation,
      defining target volumes, and suggested beam configurations. Outcome from pilot
      clinical trials, with emphasis on the impact of volume and dose on tumor response
      and treatment morbidity is discussed.

PMID- 14586833
TI  - Systemic therapy for colorectal cancer: focus on newer chemotherapy and novel
      agents.
AB  - Systemic therapy for metastatic colorectal cancer is evolving rapidly after many
      years without significant change. Standard adjuvant therapy for rectal cancer, on
      the other hand, remains much the same as it has been since the early 1990s.
      Recent additions to the colorectal cancer armamentarium include capecitabine,
      irinotecan, and oxaliplatin. Use of these agents in metastatic colorectal cancer
      and potential for use in localized rectal cancer are discussed. In addition to
      these "classical" chemotherapeutic agents, there are a number of exciting
      therapies designed to target specific molecular features of malignant cells.
      These agents are now being tested in colorectal cancer in addition to
      chemotherapy and to radiotherapy, with the hope that improvements in outcome will
      be made without substantial increases in treatment toxicity. The focus of the
      section on newer classes of agents will be on agents that are in phase II and III
      trials, with brief mention of other exciting treatment strategies.

PMID- 14586834
TI  - Chemotherapeutic and biologic agents as radiosensitizers in rectal cancer.
AB  - Over the past 25 years, important advances have been made in the management of
      patients with resectable rectal cancer. Clinical studies have shown the efficacy
      of combined chemoradiation therapy in enhancing resectability and sphincter
      preservation rates, decreasing local recurrence, and improving survival of
      patients with rectal cancer. Although 5-fluorouracil (5-FU) remains the standard
      chemotherapeutic agent used concurrently with radiation therapy, newer
      chemotherapeutic agents including capecitabine, irinotecan, and oxaliplatin have
      also been studied as radiosensitizers in this setting. Novel targeted biologic
      agents including celecoxib and bevacizumab are being explored in combination with
      standard chemotherapy and radiation therapy. In this review, we will discuss the
      mechanism of action and the key clinical studies of each agent as a
      radiosensitizer.

PMID- 14586835
TI  - The impact of radiation on functional outcomes in patients with rectal cancer and
      sphincter preservation.
AB  - Radiation therapy (RT) plays an important role in the management of patients with
      rectal cancer. However, there is mounting evidence that RT results in functional
      changes. The purpose of this study was to review the published data on bowel and
      sexual functional changes associated with RT and to determine the optimal
      strategy. The data suggest that studies are generally small, retrospective
      studies, use various RT regimens, and assess function with various
      nonstandardized parameters. In general, bowel function as measured by frequency,
      urgency, evacuation, sensation, and/or continence is impaired after RT when
      compared with patients not treated with RT. Although limited, preoperative RT
      tends to cause less impairment than postoperative RT. Sexual function is poorly
      studied, but data suggest that RT has a negative impact in both men and women.
      Further study is necessary to understand the extent of impairment, optimize
      radiation strategies, and select patients who will gain the most with RT.

PMID- 14586844
TI  - Minimally invasive oral and maxillofacial surgery: rational advancement of
      technology.

PMID- 14586845
TI  - Dental extractions in the irradiated head and neck patient: a retrospective
      analysis of Memorial Sloan-Kettering Cancer Center protocols, criteria, and end
      results.
AB  - BACKGROUND: This study was designed to use our institutional experience with
      irradiated head and neck patients to evaluate 1) dental extraction incidence and
      sequelae; 2) those patients who developed osteoradionecrosis via extraction and
      the efficacy of hyperbaric oxygen therapy; and 3) guidelines for extraction
      protocols in this population. Materials and methods A group of 1,194 patients
      with a history of radiation to the head and neck, who were evaluated and treated
      in the Dental Service at Memorial Sloan-Kettering Cancer Center, were reviewed.
      The 187 who required dental extractions were analyzed using patient demographics,
      tumor location, staging, histopathology, radiation dosage, field, and timing,
      dental extraction indications, location, surgical methods, and sequelae. RESULTS:
      Almost 85% of the patients reviewed did not require extraction. Only 4 of those
      who underwent extractions at Memorial Sloan-Kettering Cancer Center developed
      osteoradionecrosis. CONCLUSIONS: The use of multidisciplinary team communications
      and careful extraction selection by prognosis and symptomatology regardless of
      preexisting dental pathologies, atraumatic extraction procedures, and meticulous
      follow-up can lower both extraction and osteoradionecrosis rates.

PMID- 14586846
TI  - Primary malignant melanoma of the oral mucosa.
AB  - PURPOSE: The occurrence of primary oral melanoma is very rare. Large clinical
      series suggesting appropriate treatment modalities are lacking; the clinician has
      to rely on case reports to gain insight into the management of this tumor, which
      is much more aggressive than its skin counterpart. Patients and methods The cases
      of 5 patients with primary oral melanoma during a 6-year period were
      retrospectively reviewed. Four patients presented with tumors located in the
      maxilla. Preoperative workup included microscopic examination of incisional
      biopsy specimens for the confirmation of the diagnosis and thorough imaging of
      the body to rule out distant metastases. Histologically significant vertical
      invasion was found in all patients. No patient had distant metastases initially,
      and only 1 patient presented with neck disease. Primary treatment included wide
      local excision in 4 patients and therapeutic modified radical neck dissection in
      the 1 patient with neck node involvement on presentation. One patient was treated
      primarily with radiation therapy due to medically compromised status. Adjuvant
      immunochemotherapy (DAV protocol) was administered to 4 patients. Radiation
      therapy was used in an adjuvant fashion in 3 patients. RESULTS: All of the
      patients developed distant metastases to the lung and liver and eventually died
      of their disease. Survival ranged from 14 to 38 months (mean, 25.6 months). Local
      recurrence occurred in 1 patient and was attributed to positive surgical margins.
      Contralateral neck disease developed in the patient who underwent therapeutic
      neck dissection. CONCLUSIONS: The prognosis of primary oral melanoma remains poor
      despite adequate locoregional control of the disease. It seems that diagnosis is
      made late in the course of the disease when the primary tumor has already shed
      microscopic distant metastases.

PMID- 14586847
TI  - Trends in the characteristics of maxillofacial fractures in Nigeria.
AB  - PURPOSE: The study purpose was to assess the changes in the pattern of
      maxillofacial fractures in 2 different study periods. PATIENTS AND METHODS: We
      conducted retrospective study of 341 patients treated for maxillofacial fractures
      between January 1978 and December 1982 and a prospective study of 483 patients
      treated between January 1995 and December 1999 at the Department of Oral and
      Maxillofacial Surgery, University College Hospital, Ibadan, Nigeria. Data were
      collected on age, gender, etiologic factor, and site of injury. RESULTS: The male
      to-female ratio reduced in the second period by a factor of 2.0. Patients in the
      age groups of 21 to 30 years and older than 60 years increased by a factor of 1.8
      and 2.9, respectively, in the second period. Assaults, falls, sporting injuries,
      and industrial accidents in the second period increased by a factor of 1.4, 1.5,
      3.5, and 1.5, respectively. The ratio between road traffic accidents and other
      causes changed from 3.4:1 to 2.2:1 in the second period. Mandibular fractures
      increased by 2% in the second study period. CONCLUSION: The data confirmed that
      although other etiologic factors are increasing in number, road traffic accidents
      remains the major etiologic factor of maxillofacial fractures in Nigeria. There
      is a need to enforce seat belt use, speed limit, and drink driving laws to reduce
      maxillofacial injuries caused by road traffic accidents; to organize preventive
      programs to minimize assaults, and to legislate the wearing of headgear by
      industrial workers.

PMID- 14586848
TI  - Ultrasound: assessment of the distraction osteogenesis wound in patients
      undergoing mandibular lengthening.
AB  - PURPOSE: Common methods of assessment of the clinical distraction osteogenesis
      (DO) wound consist of serial physical examinations, plain radiographs, and
      computed tomography (CT). Ultrasound (US) is an inexpensive and efficient method
      of imaging that provides detailed assessment of bone formation across a defect.
      It has proved to be useful for the evaluation of long bone DO healing. The
      purpose of this study was to determine the efficacy of US for evaluation of bone
      formation in the mandibular distraction wound. PATIENTS AND METHODS: Ten patients
      underwent mandibular expansion (18 sides) with semiburied, unidirectional
      distraction devices. The wounds were assessed with plain radiographs and US
      immediately before device removal. Estimates of bone formation, using a
      semiquantitative bone fill score, were made for plain radiographs and US. US beam
      penetration depth, in millimeters, was also measured. During removal of the
      distraction device, bone formation and mandibular stability were assessed by the
      surgeon and graded on a semiquantitative scale. RESULTS: US bone fill scores
      correlated with intraoperative assessment of bone formation and stability (r =
      0.758, P =.0018) at all 18 mandibular sites. Plain radiographic scores also
      correlated with bone formation (r = 0.592). However, in 14 of 18 sides, plain
      radiographs underestimated bone formation compared with US and operative
      findings. CONCLUSION: The results of this study indicate that US is an accurate
      noninvasive technique that may prove to be useful in assessing the mandibular DO
      regenerate in patients.

PMID- 14586849
TI  - The temporal fasciocutaneous island flap for oncologic oral and facial
      reconstruction.
AB  - PURPOSE: This study reports the anatomy, operative technique, and postoperative
      results of the temporal fasciocutaneous island flap (TFCIF), as used for facial
      and intraoral reconstruction. MATERIALS AND METHODS: Retrospective study of 15
      patients who underwent TFCIF reconstruction. The anatomic basis and surgical
      technique are described. The flap was used for mucosal reconstruction after cheek
      or maxillary resection. It was used for facial tissue loss in 2 cases: orbital
      osteoradionecrosis and exposure of a mandibular reconstruction plate. RESULTS:
      This technique provides a safe and rapid solution for intraoral reconstruction;
      however, it cannot be used for the anterior floor of the mouth. The best
      indication that we have found is the reconstruction of hemimaxillectomy, allowing
      closure of buccosinusonasal communication and prosthetic rehabilitation. The main
      disavantage is that hair regrowth limits its use to patients who need
      postoperative radiotherapy. Donor site morbidity is minimal. Only a partial
      failure was observed. CONCLUSION: The TFCIF is a rapid, safe, and useful flap for
      oral and facial reconstruction after oncologic resection. Its arc of rotation
      limits, however, its use to the posterior part of the oral cavity.

PMID- 14586850
TI  - The presence of bacteria in the synovial fluid of the temporomandibular joint and
      clinical significance: preliminary study.
AB  - PURPOSE: The objective of this study was to find any relation between the
      presence of specific bacterial species in the synovial fluid of the
      temporomandibular joint (TMJ) and clinical parameters. PATIENTS AND METHODS: We
      studied 43 patients (male-to-female ratio, 1:1.69; average age, 34.37 +/- 14.55
      years). Thirty-three patients had a displaced disc in the TMJ (DD group), and 10
      patients did not have a displaced disc of the TMJ or any symptom related to TMJ
      disorders (NDD group). Clinical examinations were made to determine maximum mouth
      opening, joint sounds, previous trauma history, systemic disease, and TMJ pain.
      Six bacterial species that were reported in other studies were chosen to evaluate
      the presence of bacteria in the TMJ for this study. RESULTS: Mycoplasma
      genitalium was most frequently detected in synovial fluid (86.0%). Staphylococcus
      aureus, Mycoplasma fermentans/orale, Actinobacillus actinomycetemcomitans, and
      Streptococcus mitis were detected in 51.2%, 37.2%, 25.6%, and 7.0% of samples,
      respectively. beta-Hemolytic Streptococcus was not detected. The prevalence of S
      aureus was significantly higher in the DD group than in the NDD group (P <.05).
      The patients who had M. fermentans/orale were 5.40 times more likely to be
      younger than 30 years than were those without M. fermentans/orale (P <.05). Those
      with M. genitalium were 5.81 times more likely to be female than were those
      without M. genitalium (P <.05). CONCLUSION: The presence of S. aureus in TMJ
      synovial fluid was related to TMJ disorder symptoms and clinical parameters
      seemed to be influenced by bacterial presence in TMJ synovial fluid.

PMID- 14586851
TI  - Are internal derangement and osteoarthrosis linked to changes in clinical outcome
      measures of arthrocentesis of the temporomandibular joint?
AB  - PURPOSE: Arthrocentesis and hydraulic distention of the temporomandibular joint
      (TMJ) have been described as an effective modality in the treatment of patients
      with clinical findings consistent with the diagnosis of disc displacement without
      reduction. The purpose of this study was to investigate whether the magnetic
      resonance (MR) imaging variables of internal derangement (ID) and osteoarthrosis
      (OA) and the presence of capsulitis/synovitis (C/S) may be linked to changes in
      TMJ signs and symptoms associated with the performance of arthrocentesis and
      hydraulic distention. PATIENTS AND METHODS: The study consisted of 27 TMJ pain
      patients, who were assigned a clinical unilateral TMJ diagnosis of ID type III
      (disc displacement without reduction). Bilateral sagittal and coronal MR images
      were obtained immediately preoperatively and at a 2-month follow-up to establish
      the presence or absence of ID and OA. TMJ pain level of function and mandibular
      range of motion were assessed preoperatively and compared with the respective 2
      month follow-up findings. RESULTS: The pretreatment data revealed a significant
      relationship between the clinical finding of TMJ pain and the MR imaging findings
      of ID (P <.001), ID type (P <.001), and OA (P <.05). At 2-month follow-up,
      clinical evaluation showed a significant reduction in TMJ pain during function (P
      <.001), a significant reduction in the clinical diagnoses of ID type III (P
      <.05), and a significant increase in mandibular range of motion (P <.05). There
      was no change in the prevalence rates of associated MR imaging diagnoses of TMJ
      ID and/or OA. CONCLUSION: The study findings suggest that clinical pain is
      related to TMJ-related MR imaging findings of ID and OA. These diagnoses proved
      not to be linked to changes in therapeutic outcome measures of TMJ pain and
      mandibular range of motion.

PMID- 14586854
TI  - Sternocleidomastoid myocutaneous flap for intraoral reconstruction after
      resection of oral squamous cell carcinoma.
AB  - PURPOSE: The sternocleidomastoid (SCM) myocutaneous flap remains an important
      tool in head and neck reconstruction. This article retrospectively reviews 40
      consecutive SCM myocutaneous flaps used for the reconstruction after resection of
      oral squamous cell carcinoma with respect to reliability and complications.
      PATIENTS: From 1987 to 1997, 40 patients underwent SCM myocutaneous flap
      reconstruction of the oral cavity. The age and gender of the patients, site of
      primary tumor TNM stage, type of associated operation, and clinical course were
      analyzed. RESULTS: In 8 cases, partial epithelial loss over the skin paddle
      occurred with survival of the muscle and at least some of the dermis. Unilateral
      supraomohyoid neck dissection (SND) was performed in 11 cases, and unilateral
      functional neck dissection, which preserves SCM and/or internal jugular vein
      and/or accessory nerve, in 16 cases. Pathologically positive nodes were
      recognized in 14 of these 27 neck dissection cases; in 11 of these 14 cases, the
      neck lesion was controlled. CONCLUSION: The SCM myocutaneous flap appears to be
      simple to use and useful for reconstruction of the defect after resection of oral
      carcinoma, and the indications for this flap will be extended in accordance with
      the recent increases in the number of supraomohyoid and functional neck
      dissection cases.

PMID- 14586855
TI  - Factors influencing the resonance frequency of dental implants.
AB  - PURPOSE: Resonance frequency (RF) analysis has been used by several investigators
      to assess the boundary conditions of dental implants. However, a scientific
      investigation of the association between the structural condition of the alveolar
      bone and the dynamic behavior of dental implants has not yet been reported. The
      aim of this study was to assess the factors influencing the RF of dental implants
      using an in vitro modal analysis. MATERIALS AND METHODS: Resonant vibration
      within implants was induced by an impulse-force hammer. The induced vibration
      signal was subsequently detected using an acoustic microphone and analyzed by
      fast Fourier transform. The resultant data were further analyzed to test the
      statistical effects of the embedding-material boundary height, thickness, and
      density on the RF values of the sample implants. RESULTS: Significant changes (P
      <.05) in RF values were revealed for implants embedded within a high-density
      block when decreasing boundary height reached 6, 5, and 4 mm, at respective
      thickness increments of 10, 15, and 20 mm. For analogous low-density samples,
      significant changes (P <.05) in RF values were found when respective decreasing
      boundary height reached 6, 4, and 3 mm. CONCLUSIONS: Our findings indicate that
      boundary height, width, and density factors can influence the RF of dental
      implants and that a lower boundary density and greater boundary thickness can
      lead to more obvious RF changes.

PMID- 14586853
TI  - Interleukin-1beta, interleukin-1 receptor antagonist, and interleukin-1 soluble
      receptor II in temporomandibular joint synovial fluid from patients with chronic
      polyarthritides.
AB  - PURPOSE: The aim of this study was to investigate whether interleukin-1beta (IL
      1beta), interleukin-1 receptor antagonist (IL-1ra), or soluble IL-1 receptor II
      (sIL-1RII) in synovial fluid or plasma is associated with joint pain or signs of
      tissue destruction in patients with temporomandibular joint (TMJ) involvement of
      polyarthritides. PATIENTS AND METHODS: Forty-three patients with TMJ involvement
      of polyarthritides were included. TMJ resting pain, tenderness to palpation,
      pressure pain threshold, pain on mandibular movement, and anterior open bite were
      assessed. TMJ synovial fluid samples and plasma were obtained for analysis of IL
      1beta, IL-1ra, and sIL-1RII. RESULTS: IL-1beta was detected in 18% of the
      synovial fluid samples and in 44% of the plasma samples. The concentrations of IL
      1ra in plasma were lower than in the synovial fluid, whereas the opposite
      condition was found for sIL-1-RII. IL-1ra in synovial fluid and plasma was
      associated with low intensity of TMJ pain. sIL-1RII in synovial fluid was
      associated with low degree of anterior open bite, whereas sIL-1RII in plasma was
      associated with widespread musculoskeletal pain, TMJ pain and tenderness, and
      decreased pressure pain threshold over the TMJ. CONCLUSION: IL-1ra and sIL-1RII
      are present in different proportions in TMJ synovial fluid and blood plasma from
      patients with TMJ involvement of polyarthritis. Both of these molecules seem to
      influence the clinical features of these forms of TMJ inflammation.

PMID- 14586856
TI  - Correlation of immunohistochemical characteristics of the craniomandibular joint
      with the degree of mandibular lengthening in rabbits.
AB  - PURPOSE: This study examined immunohistochemical changes in the craniomandibular
      joints of rabbits after distraction osteogenesis following mandibular
      corticotomy. MATERIALS AND METHODS: The experimental animals (n = 8) were divided
      into 3 groups that underwent 2, 3.5, and 5 mm of unilateral distraction
      osteogenesis (groups 1, 2, and 3, respectively). After corticotomy of the left
      mandibular body and a 7-day healing period, a second operation was performed to
      expose the device. Distraction was then performed at the rate of 0.5 mm/d. A 14
      day consolidation period was allowed after the distraction was complete. Changes
      in cartilage, osteoblast activity, and osteoclast activity were then examined.
      RESULTS: The differentiation and proliferation of cartilage increased in groups 1
      and 2, were highest in group 2, and decreased in group 3. Group 2 also showed the
      greatest increase in the width of the hypertrophic chondrocyte layer. Relative to
      the control group, osteoclast activity was only somewhat higher in groups 1 and 2
      but was significantly higher in group 3. Osteoblast activity was significantly
      higher in groups 1 and 2 than in the control group. However, the osteoblast
      activity in group 3 was slightly lower than that in group 2. At the time of
      unilateral mandibular distraction, no degenerative changes of the
      temporomandibular joint were observed in groups 1 or 2, but bone resorption was
      observed in group 3. CONCLUSIONS: The unilateral mandibular distraction of 2 or
      3.5 mm was acceptable in that no degenerative changes of the temporomandibular
      joint were observed on either the distraction or the nondistraction sides. Five
      millimeters of distraction might be beyond physiologic limits.

PMID- 14586857
TI  - Concomitant temporomandibular joint and orthognathic surgery.

PMID- 14586858
TI  - Simultaneous temporomandibular joint and orthognathic surgery: the case against.

PMID- 14586859
TI  - An overview of facial aesthetic units.

PMID- 14586860
TI  - The person behind the name: part 2.

PMID- 14586861
TI  - Ewing's sarcoma of the mandibular condyle: report of a case.

PMID- 14586862
TI  - Dentofacial deformity secondary to a severe trauma of the middle third of the
      face in infancy.

PMID- 14586863
TI  - Primary malignant fibrous histiocytoma of the mandible: review of literature and
      report of a case.

PMID- 14586864
TI  - Clinical application of the temporoparietal-galeal flap in closure of a chronic
      oronasal fistula: review of the anatomy, surgical technique, and report of a
      case.

PMID- 14586865
TI  - A method to control epistaxis after nasal antrostomy and Caldwell-Luc procedure.

PMID- 14586866
TI  - Interventional sialendoscopy: a new procedure for noninvasive insertion and a
      minimally invasive sialolithectomy.

PMID- 14586867
TI  - Efficacy of the brush biopsy.

PMID- 14586868
TI  - Avascular necrosis of the jaws: risk factors in metastatic cancer patients.

PMID- 14586869
TI  - Azithromycin for odontogenic infection.

PMID- 14586872
TI  - Controversies in the management of hepatitis C virus infection after liver
      transplantation.
AB  - Recurrence of hepatitis C virus infection after liver transplantation is
      universal. A significant percentage of these patients develop progressive graft
      injury and cirrhosis. Those factors that modulate disease progression in liver
      transplant recipients with recurrent hepatitis C virus infection remain
      controversial and are poorly understood. Treatment of recurrent hepatitis C virus
      after liver transplantation with either interferon or interferon and ribavirin
      has yielded only limited success. Regardless of this, treatment is instituted.
      Peginterferon is more effective than standard interferon for treatment of chronic
      hepatitis C virus infection in the nontransplantation setting when used either
      alone or with ribavirin. The effectiveness of peginterferon, both with and
      without ribavirin in the posttransplantation setting, is currently being
      explored. In this review those factors thought to affect disease progression in
      patients with recurrent hepatitis C virus will be discussed, strategies that have
      been used to treat recurrent hepatitis C virus will be reviewed, and the impact
      that peginterferon may have on hepatitis C virus infection in the
      pretransplantation and posttransplantation setting will be explored.

PMID- 14586873
TI  - Cognitive dysfunction and health-related quality of life in long-term liver
      transplant survivors.
AB  - Although several studies have investigated short-term effects of liver
      transplantation on cognitive function and health-related quality of life, there
      have been no studies looking at long-term effects. Patients who received a single
      liver transplant at St James's University Hospital (Leeds, UK) before October 1,
      1991, were invited to participate in this cross-sectional study. Cognitive
      function was assessed using the Mini-Mental State Examination, the Rey Auditory
      Verbal Learning Test, trail-making tests, the Stroop test, and the Benton Visual
      Retention Test. Anxiety and depression were documented using the Hospital Anxiety
      and Depression Scale. Health-related quality of life was assessed using the
      EuroQol. Twenty-five healthy volunteers acted as controls. Thirty-six patients
      had undergone transplantation before October 1, 1991. Thirteen patients (36%) had
      died, 6 patients had received more than one transplant, 2 patients did not speak
      English, and 3 patients did not want to participate, leaving 12 patients included
      in the study. Patients scored significantly lower on measures of health-related
      quality of life than healthy controls, but there were no differences in levels of
      anxiety or depression. Patients scored significantly lower than controls across a
      wide range of cognitive functions, suggesting global cognitive impairment. We
      show that patients who survive for more than 10 years after liver transplantation
      have significant cognitive dysfunction and poor health-related quality of life.
      Whether these patients never return to normal after transplantation or whether
      they experience an increased rate of decline in cognitive function and health
      related quality of life is uncertain and requires further study.

PMID- 14586874
TI  - Liver transplantation: what do we really know about the long-term impact?

PMID- 14586875
TI  - Delayed onset of severe hepatitis C-related liver damage following liver
      transplantation: a matter of concern?
AB  - Although histological hepatitis occurs in the majority of hepatitis C virus (HCV)
      infected liver transplant recipients, the natural history is highly variable.
      Whereas progression to cirrhosis occurs in up to 30% after 3 to 7 years, the
      disease remains stable in another third of patients, in whom protocol liver
      biopsies might be avoided. However, there is recent concern that with prolonged
      follow-up, some patients with initial benign recurrence may develop a late-onset
      aggressive course. Aims of the study are to determine the incidence and factors
      associated with this event. Based on yearly protocol biopsies (median, five
      biopsies; range, three to seven biopsies), we evaluated the histological outcome
      of 57 HCV type 1b-infected transplant recipients with initial benign recurrence,
      defined as stable histological state (fibrosis stage F0 or F1) during the first 3
      years posttransplantation. Severe late-onset liver damage is defined as
      progression to F3 or F4 in patients with previous benign recurrence. Potential
      predictors of this event include demographics, donor-related factors, liver
      enzyme levels at 1 and 3 (or baseline) years posttransplantation, activity grade
      and fibrosis stage at 1 and 3 years posttransplantation, nonalcoholic
      steatohepatitis-related variables occurring within the first 3 years
      posttransplantation (diabetes, hyperlipidemia, obesity), use of some drugs (renin
      angiotensin inhibitors, ursodeoxycholic acid), and the advent of any unusual
      event. The incidence of severe late-onset liver damage was 35% (n = 20). Twelve
      transplant recipients progressed to F3, whereas 8 transplant recipients
      progressed to F4. Sudden histological deterioration was observed on postoperative
      biopsy 5 in 12 patients; biopsy 6 or 7, in 7 patients; and biopsy 4, in 1
      patient. Variables associated with this event in univariate analysis were
      fibrosis stage and activity grade (and its components) at baseline (P <.0001),
      recipient female gender (P =.04), alanine aminotransferase (ALT) level at 1 year
      posttransplantation (P =.02), and aspartate aminotransferase (AST) and ALT levels
      at baseline (P =.008 and P =.005, respectively). By multivariate analysis, only
      one variable was retained in the model: fibrosis stage at baseline (relative
      risk, 11; 95% confidence interval, 3 to 41; P =.0007), whereas AST level almost
      reached statistical significance (P =.07). In conclusion, delayed HCV-related
      severe liver damage is not infrequent in transplant recipients with initial
      benign recurrence, occurring in approximately one third of them. The presence of
      some degree of fibrosis at baseline appears to predict this sudden change in the
      natural history of recurrent hepatitis C. Based on these findings, we recommend
      continuing protocol biopsies and evaluating potential antiviral therapy in
      transplant recipients with evidence of some fibrosis (even if it is only portal).

PMID- 14586876
TI  - Hepatitis C virus therapy, hepatocyte drug metabolism, and risk for acute
      cellular rejection.
AB  - We recently reported on a series of patients who experienced acute cellular
      rejection (ACR) during the treatment of hepatitis C virus (HCV) infection in our
      posttransplantation cohort. Our hypothesis is that HCV clearance improves hepatic
      microsomal function, which in turn results in lower trough cyclosporine (CyA) and
      tacrolimus (TAC) levels, predisposing the patient to ACR. Records of all patients
      receiving transplants for HCV infection at our center from 1993 to June 2002 were
      reviewed. Two hundred three patients were identified. Thirty-seven patients (18%)
      were treated with interferon-based therapies in combination with ribavirin.
      Twelve patients were selected for analysis because they became HCV RNA negative
      during therapy, and 18 patients with no antiviral response were selected as
      controls (7 other patients had incomplete data or had switched from one
      immunosuppression [IS] therapy to the other). Baseline IS levels were compared
      with the first available level after documented negative HCV RNA results in the
      study group and the last on-treatment IS level in the control group. We also
      compared frequency and percentage of change in IS levels during therapy. Mean
      decline in CyA trough levels in the study group was from 187.28 ng/mL at baseline
      to 118.14 ng/mL immediately after becoming HCV RNA negative (-36.92%; P =.018).
      Mean decline in TAC levels was from 7.34 ng/mL at baseline to 5.02 ng/mL
      immediately after becoming HCV RNA negative (-29.17%; P =.044). Overall, 6 of 12
      patients who cleared HCV RNA during therapy experienced ACR; 1 patient died as a
      result of ACR. Using percentage of decrease from baseline IS level, we combined
      results for patients administered CyA and TAC and found a significant decrease
      from baseline IS levels in responders (-31.8% after HCV RNA clearance on
      treatment; P =.0001). Nonresponders experienced a 0.98% decline in IS levels
      while on treatment, and the difference was significant compared with the change
      in the responder group (P =.006). A greater proportion of antiviral therapy
      responders also experienced trough IS levels 20% less than baseline than
      nonresponder controls during therapy (P =.0006). In conclusion, IS levels
      decreased significantly in patients responding favorably to anti-HCV therapy.
      This decrease in IS levels may have a key role in predisposing these patients to
      ACR.

PMID- 14586877
TI  - Osteopenia and osteoporosis in patients with end-stage liver disease caused by
      hepatitis C and alcoholic liver disease: not just a cholestatic problem.
AB  - Although best characterized in chronic cholestatic liver disease, osteopenic bone
      disease and fracturing are well-recognized complications of cirrhosis,
      particularly after liver transplantation. We sought to compare the prevalence of
      osteopenia and osteoporosis, to assess the effect of orthotopic liver
      transplantation (OLT) on bone density, and to determine fracture rates before and
      after OLT in three groups of patients with advanced cirrhosis: patients with
      cirrhosis from hepatitis C virus (HCV) alone, from alcohol abuse (ALD), and from
      HCV in conjunction with alcohol abuse (HCV+ALD). Between 1991 and 2001, 207
      consecutive patients who underwent OLT for HCV (68 patients), ALD (66), and
      HCV+ALD (73) were assessed clinically, biochemically, radiologically, and by bone
      densitometry. The baseline mean T score was lower in the HCV group than in the
      ALD group (-1.43 versus -0.87, P =.048) despite ALD patients having more advanced
      liver disease; patients with HCV+ALD had intermediate T scores. The pattern of
      significant bone loss at 4 months and 12 months was similar for all three groups.
      The baseline fracture rate was lowest in the HCV group and highest in the ALD
      group, despite the latter having the highest bone density. Fractures occurred in
      17% of patients in the first year after transplantation, the majority being
      vertebral compression fractures. Patients with cirrhosis caused by HCV, ALD, or a
      combination of both should be screened for osteopenia, especially before OLT.

PMID- 14586878
TI  - Long-term survival of recipients of liver grafts from donors older than 80 years:
      is it achievable?
AB  - Isolated cases or small series of orthotopic liver transplantation (OLT) with
      grafts from donors older than 80 years have been reported, but the long-term
      outcome of patients receiving livers from extremely old donors is unknown. From
      1998 to 2003, we performed 17 OLTs with donors older than 80 years (median, 82
      years; range, 80 to 87 years). No deaths occurred in the early postoperative
      period. We analyzed the outcome in 12 patients with a follow-up longer than 1
      year. Hepatic insufficiency was caused by hepatitis C virus (HCV)-related
      cirrhosis in five cases (42%) and non-HCV-related diseases in seven cases (58%).
      All donors had normal liver function, hemodynamic stability, and no parenchymal
      alterations. OLT was uneventful in all cases. Median follow-up was 30.3 months
      (range, 17 to 42 months). No late vascular complications occurred. One patient
      (8.3%) died 3 years after OLT for causes unrelated to hepatic dysfunction. Two-
      and 3-year actuarial survival rates were 100% and 75%, respectively. All HCV
      positive (HCV(+)) patients developed hepatitis recurrence (after 2, 3, 4, 5, and
      22 months) requiring antiviral treatment in 3 patients and leading to graft
      cirrhosis in 1 patient. Non-HCV(+) patients had well-preserved liver function
      throughout the observation period. At the end of follow-up, we observed no
      clinical hepatic decompensation in the entire group and biochemical signs of
      recurrent disease in 3 patients. Use of grafts for OLT from donors older than 80
      years is safe because of their potentially normal functional recovery. A
      selection among available organs is mandatory to minimize other risk factors for
      poor outcome. Long-term patient and graft survival seem to be achievable, but the
      high rate and rapidity of HCV reinfection remain a major concern for HCV(+)
      patients.

PMID- 14586879
TI  - Living donor liver transplantation for hepatitis B cirrhosis.
AB  - The living donor liver transplantation (LDLT) experience for patients with
      hepatitis B virus (HBV) infection is still limited. Because LDLT can be performed
      electively, it can provide an appropriate length of time to reduce HBV DNA levels
      before the operation. This study aims to examine the feasibility of our protocol
      for preventing HBV reinfection after LDLT. Of 20 patients analyzed, 15 patients
      had detectable serum HBV DNA when referred to our hospital. Thirteen patients had
      hepatocellular carcinoma. All patients were treated with lamivudine (100 mg/d)
      before LDLT. After LDLT, hepatitis B immunoglobulin (HBIG) was administered to
      maintain serum antibody to hepatitis B surface antigen titers at greater than
      1,000 IU/mL for 1 year and 200 IU/mL thereafter. Lamivudine was not administered
      postoperatively, except for three patients with detectable serum HBV DNA just
      before LDLT. All patients survived the operation. One patient died 229 days after
      LDLT of carcinoma recurrence. In the other 19 patients, liver function has
      remained normal and no viral relapse occurred postoperatively during a median
      follow-up of 19 months. Perioperative use of lamivudine and indefinite HBIG
      administration in the postoperative period might be a rational strategy for
      preventing HBV reinfection after LDLT.

PMID- 14586880
TI  - Live donor liver transplantation for fulminant hepatic failure in children.
AB  - The mortality rate among children with fulminant hepatic failure (FHF) on the
      waiting list for cadaveric donor liver transplantation (CDLT) is high. Results of
      emergency CDLT in this situation often are unsatisfactory, and a long-term
      survival rate less than 30% has been reported. Live donor liver transplantation
      (LDLT) for FHF in children has been advocated, but is reported rarely. We present
      our experience with LDLT in children with FHF. Between September 1993 and
      December 2002, primary LDLT was performed for 26 children; 8 of these children
      had FHF. Patient demographics, clinical and laboratory data, surgical details,
      complications, and graft and patient survival are reviewed. Four boys and four
      girls received left-lateral segment (n = 7) and full left-lobe (n = 1) grafts.
      Mean age was 2.9 +/- 1.2 years (range, 3 months to 11 years). Causes of FHF were
      drug induced in 2 patients and idiopathic in 6 patients. One child received a
      blood group-incompatible graft. Two patients died; 1 patient of cytomegalovirus
      infection at 8.6 months and 1 patient of recurrent hepatitis of unknown cause at
      2.8 months after LDLT. The child who received a mismatched graft had refractory
      rejection and underwent a second LDLT with a blood group-compatible graft 19 days
      afterward. He eventually died of lymphoproliferative disease. Another patient
      developed graft failure related to venous outflow obstruction and survived after
      retransplantation with a cadaveric graft. With a median follow-up of 13.2 months
      (range, 2.8 to 60.3 months), actuarial graft and patient survival rates were 50%
      and 62.5%, respectively. Survival results appear inferior compared with those of
      18 children who underwent LDLT for elective conditions during the same study
      period (graft survival, 89%; P =.051; patient survival, 89%; P =.281). Although
      survival outcomes are inferior to those in elective situations, LDLT is a timely
      and lifesaving procedure for children with FHF.

PMID- 14586881
TI  - Are preformed antibodies to biliary epithelial cells of clinical importance in
      liver transplantation?
AB  - During acute liver allograft rejection, most of the tissue damage to bile duct
      epithelium is thought to occur as a consequence of direct immunologic injury by T
      cell-mediated immune effector mechanisms. However, the role of antibodies to
      biliary epithelial cells (BECs) in liver transplant rejection is not known. We
      therefore investigated cross-match sera obtained immediately before liver
      transplantation from 95 patients for the presence of BEC-reactive antibodies to
      determine their association with acute rejection. BECs were isolated from one
      normal healthy liver. Antibody binding was detected by using flow cytometric
      analysis. Donor lymphocyte-specific cross-matches using complement-dependent
      cytotoxicity (CDC) and flow cytometric assays also were performed. The 2-year
      patient survival rate in this study was 86.3%. Eleven patients were positive for
      either CDC or flow cytometric cross-matches. BEC antibodies were detected in 41
      serum samples (43.2%). Patients with BEC antibodies experienced acute rejection
      more frequently (65.9%) compared with 42.5% without antibodies (P <.03). HLA
      specificity determinations indicated that in 5 of 41 cases, anti-BEC reactivity
      was caused by HLA antibodies. No correlations between the presence of BEC
      antibodies and patient survival and the occurrence of cholangitis and nonsurgical
      bile duct strictures were found within 2 years of follow-up. In conclusion,
      preformed antibodies to BECs are associated with acute rejection. Thus, the
      presence of these antibodies before transplantation may facilitate acute liver
      graft rejection.

PMID- 14586882
TI  - Bile secretory function after warm hepatic ischemia-reperfusion injury in the
      rat.
AB  - Hepatic ischemia-reperfusion (I-R) injury frequently is associated with
      cholestasis. However, the underlying mechanisms are not fully understood. The aim
      of the study is to assess bile secretory function in vivo in rats subjected to
      warm lobar hepatic ischemia at different times during reperfusion. A model of
      lobar 70% warm hepatic ischemia for 30 minutes was used with studies conducted at
      1 and 6 hours and 1, 3, and 7 days after reperfusion. Bile secretory function was
      assessed after selective cannulation of bile ducts of ischemic (ILs) and
      nonischemic lobes (NILs). Serum activity of hepatic alanine and aspartate
      aminotransferase was slightly increased in rats subjected to I-R, whereas serum
      bile salt levels increased early during reperfusion, returning to control values
      after 7 days. ILs showed mild reversible leukocyte infiltration and no
      significant necrosis. Bile flow and bile salt excretion were significantly
      decreased in ILs during the first 24-hour reperfusion period compared with sham
      operated rats and NILs. A marked reduction in glutathione (GSH) excretion
      occurred at 1 and 6 hours and 1 and 3 days, which returned to control values
      after 7 days. Total GSH and both reduced and oxidized GSH levels in liver
      homogenate and arterial blood GSH levels were unchanged at all times. Protein
      mass of multidrug resistance protein 2 and its function, assessed by the hepatic
      maximum secretory rate of ceftriaxone, did not show significant changes in ILs or
      NILs compared with sham-operated rats. Liver tissue gamma-glutamyl transpeptidase
      (GGT) and gamma-glutamylcysteine synthetase activities remained unchanged,
      whereas biliary GGT and cysteine secretory rates were significantly increased in
      ILs and NILs. Administration of acivicin, a GGT inhibitor, resulted in decreased
      secretion of this enzyme into bile and a parallel marked increase in biliary GSH
      secretion compared with untreated ischemic rats. In conclusion, warm hepatic I-R
      induces reversible cholestatic changes in ILs. GSH secretory rates from both ILs
      and NILs were markedly decreased during reperfusion. The reversibility of this
      effect after GGT inhibition, as well as increased release of active GGT into bile
      and cysteine biliary secretory rates, suggest increased GSH degradation in bile.
      These findings might be relevant for the I-R-induced clinical cholestasis, as
      well as cholangiocyte injury, seen after hepatic ischemia.

PMID- 14586883
TI  - The sickest first? Disparities with model for end-stage liver disease-based organ
      allocation: one region's experience.
AB  - February 27, 2002, allocation of cadaver livers for transplantation changed from
      a waiting-time-based system to an evidence-based system referred to as the Model
      for End-Stage Liver Disease (MELD). We reviewed data from 1 of the 11 United
      Network for Organ Sharing regions to determine the impact of the MELD on the
      allocation of cadaver livers for transplantation in that region. The region of
      interest (study region) consists of three distinct geographic areas (referred to
      as Transplant Service Areas [TSAs]). Based on information obtained from the Organ
      Procurement and Transplantation Network for the United States and for the study
      region, the following observations were made: (1) study region patients who
      received a cadaver liver had higher mean and median MELD scores than cadaver
      liver recipients in the United States (study region mean score, 25.1; median,
      26.0; US mean score, 23.9; median, 24.0); (2) within the study region, TSAs with
      competing liver transplant programs performed transplantation on patients at a
      significantly higher mean MELD score than TSAs dominated by a single center (TSA
      1 mean score, 27.3; TSA-2 mean score, 26.6; TSA-3 mean score, 21.3); this
      disparity persisted when transplantations for hepatocellular carcinoma (HCC) were
      excluded; and (3) study region patients removed from the waiting list because of
      death or being too sick for transplantation have higher MELD scores than the
      national average (study region mean score, 25.4; US mean score, 23.8). Overall,
      implementation of the MELD resulted in a substantial increase in the number of
      transplantations performed for HCC, and MELD exceptions for all reasons were more
      common in TSAs that have multiple centers. Despite the MELD, there remains
      disparity in organ allocation within the study region. The MELD may accurately
      predict pretransplantation mortality, but it does not ensure equitable organ
      distribution. We propose that intraregional sharing of cadaver livers based on
      the MELD may help limit disparities in organ allocation.

PMID- 14586884
TI  - Oxygen availability during orthotopic liver transplantation.
AB  - Studies have stressed the role of adequate tissue oxygenation in the light of an
      optimal patient outcome and allograft viability in liver transplantation. The
      practice of monitoring conventional hemodynamic parameters during liver
      transplantation could be complemented by parameters assessing real oxygen
      availability. In the present prospective study, real arterial available oxygen
      content (CavlO(2)) and its extraction ratio (O(2)ERavl) were calculated. These
      parameters include the effect of changes in oxyhemoglobin dissociation curve
      (ODC; expressed by P(50)) on oxygen availability, under the different
      circumstances occurring during liver transplantation. Sixteen adult cirrhotic
      patients were studied during orthotopic liver transplantation with the use of
      venovenous bypass. Classic hemodynamic measurements using a Swan-Ganz
      thermodilution catheter and arterial and mixed venous blood gas analysis were
      performed, and P(50), oxygen delivery index (DO(2 ind)), oxygen consumption index
      (VO(2 ind)), oxygen extraction ratio (O(2)ER), CavlO(2), and O(2)ERavl were
      calculated. Statistical analysis was performed using ANOVA for repeated measures
      and Spearman correlation coefficient matrix among the six variables (DO(2 ind),
      VO(2 ind), O(2)ER, P(50), CavlO(2), and O(2)ERavl) taken two at a time at every
      phase. Parameter P(50) changed from 25.98 +/- 1.10 to 23.15 +/- 2.24 (at the end
      of operation). A leftward shift of the ODC was observed. The results showed
      positive association between P(50) and CavlO(2) after the removal of the native
      liver, and a weak and inconsistent relation of DO(2 ind) with any of the other
      study variables. The intraoperative changes in P(50) values, which represent a
      shift of the ODC to the left, may reflect a more accurate estimation of O(2)
      release to the tissues, than the hemoglobin, Pao(2) and Sao(2) alone. Besides
      conventional hemodynamic parameters, P(50), which includes the effect of
      alterations in ODC on oxygen availability, could be of value in monitoring the
      systemic oxygenation during liver transplantation.

PMID- 14586885
TI  - Liver transplantation for growing teratoma syndrome: report of a case.
AB  - Liver transplantation is a well-established treatment for liver failure and for a
      selected group of patients with hepatic tumors. The growing teratoma syndrome
      refers to the phenomenon whereby germ cell tumors enlarge after chemotherapy
      despite complete eradication of malignant cells and normalization of serum tumor
      markers. We present the case of a young patient with rapidly growing teratomatous
      masses in his liver who was treated with liver transplantation from a live donor.
      We discuss his postoperative management, follow-up, and briefly review literature
      on the subject.

PMID- 14586886
TI  - Hepatocellular carcinoma extension into the right atrium.

PMID- 14586887
TI  - Vancomycin-resistant enterococcal infections: cause for concern?

PMID- 14586888
TI  - Report of the first International Liver Transplantation Society expert panel
      consensus conference on liver transplantation and hepatitis C.

PMID- 14586889
TI  - Scope of worldwide hepatitis C problem.
AB  - 1. Hepatitis C is a global health problem affecting over 170 million people
      worldwide. 2. There is wide geographic variation in both prevalence and genotype
      distribution of hepatitis C virus on a global level. 3. Most hepatitis C virus is
      spread parenterally, either through intravenous drug use or, in lesser-developed
      countries, through blood contamination during medical procedures. 4. Hepatitis C
      is a leading cause of end-stage liver disease and hepatocellular carcinoma. 5.
      Despite a declining incidence of new infections, the burden of disease, both in
      terms of mortality and in terms of cost, is expected to increase over the next
      decade.

PMID- 14586890
TI  - Natural history and risk factors for progression of hepatitis C virus disease and
      development of hepatocellular cancer before liver transplantation.
AB  - 1. Chronic infection with hepatitis C virus (HCV) is the leading cause of
      cirrhosis and the most common indication for liver transplantation in many
      countries throughout the world. 2. The most significant factors leading to
      fibrosis progression in patients with chronic HCV infection include the degree of
      inflammation present on liver biopsy and ongoing alcohol use. 3. Patients with
      cirrhosis secondary to chronic HCV infection are at increased risk for developing
      hepatocellular carcinoma (HCC). 4. Achieving a sustained virological response
      after treatment with interferon, with or without ribavirin, is associated with a
      reduced risk for the development of cirrhosis and HCC and prolonged survival.

PMID- 14586891
TI  - Impact of immunosuppression on immunopathogenesis of liver damage in hepatitis C
      virus-infected recipients following liver transplantation.
AB  - 1. Hepatitis C virus (HCV) infection in the allograft occurs in the setting of
      greater viral burdens than in patients pretransplantation. 2. Viral burden is
      increased by such immunosuppressive therapies as corticosteroids and interleukin
      2 receptor antibodies. 3. Cholestatic HCV infection occurs in the setting of very
      high viral load and is almost certainly induced by overimmunosuppression. It is
      managed best by rapid reduction in levels of immunosuppression. 4. The more
      common chronic hepatitic HCV disease seems to behave at the molecular/cellular
      level in a fashion similar to the nontransplantation setting with activation of T
      helper subtype 1 inflammatory, profibrotic, and proapoptotic pathways. The role
      of immunosuppression in the acceleration of this disease is unclear, and rapid
      reduction in immunosuppressive doses may be detrimental. 5. Changes to
      definitions of types of HCV disease recurrence, disease severity, and acute
      allograft rejection in the presence of HCV infection are required to improve
      understanding of the pathogenesis.

PMID- 14586892
TI  - The natural history and outcome of liver transplantation in hepatitis C virus
      infected recipients.
AB  - 1. Recurrence of hepatitis C infection is universal and immediate after liver
      transplantation. 2. Graft and patient survival is reduced in liver
      transplantation recipients with recurrent hepatitis C virus infection compared
      with hepatitis C virus-negative recipients. 3. The natural history of chronic
      hepatitis C is accelerated after liver transplantation compared with
      nontransplantation chronic hepatitis C; 20% to 40% of patients progress to
      allograft cirrhosis within 5 years, compared with less than 5% of
      nontransplantation patients. 4. The rate of fibrosis progression is not uniform
      and may change over time. 5. The rate of progression from cirrhosis to
      decompensation is accelerated after liver transplantation. The rate of
      decompensation is >40% at 1 year and >60% at 3 years, compared with <5% and <10%,
      respectively, in immunocompetent patients. 6. The rate of progression from
      decompensation to death is also accelerated after liver transplantation. The 3
      year survival is <10% after the onset of hepatitis C virus-related allograft
      failure, compared with 60% after decompensation in immunocompetent patients.

PMID- 14586893
TI  - Hepatitis C pathogenesis: mechanisms of viral clearance and liver injury.
AB  - 1. The development of hepatitis C virus (HCV) quasispecies has a number of
      biological consequences, including the development of escape mutants to humoral
      or cellular immunity, the generation of "defective" viral particles, variable
      cell tropism, and the development of drug resistance. 2. Accumulating evidence
      shows that HCV affects the early innate immune response mediated by natural
      killer and dendritic cells. 3. Recent data suggest that clearance of HCV bestows
      antibody to HCV immunity that affords partial protection against persistent
      infection. However, after spontaneous recovery from HCV infection, titers of HCV
      specific antibodies decline and disappear in a subset of patients, whereas viral
      specific CD4(+) and CD8(+) T-cell responses persist for decades. 4. HCV-specific
      CD8(+) T-cell responses are phenotypically and functionally diverse and may be
      associated with either viral eradication or chronic hepatic immunopathologic
      states. 5. Novel HCV genome-wide screening approaches have shown that the breadth
      of the immune response is considerably greater than was initially appreciated
      using more conventional assays, but why the majority of patients remain
      chronically infected despite the presence of viral-specific immune responses
      remains undefined.

PMID- 14586894
TI  - Host and donor risk factors before and after liver transplantation that impact
      HCV recurrence.
AB  - 1. The natural history of hepatitis C after liver transplantation is variable.
      Several factors, including those related to the virus, the host, the environment
      and the donor, are probably implicated in the outcome. 2. The immune status per
      se likely represents the main significant variable in influencing disease
      severity in hepatitis C virus-infected patients. Findings that support this
      statement include the higher aggressivity of hepatitis C in immunocompromised
      liver transplant recipients as compared with that observed in immunocompetent
      patients, both before and after the development of compensated cirrhosis, and the
      significant association described between the degree of immunosuppression and
      disease severity. 3. Similar to that observed in the immunocompetent population,
      the age at the time of infection (age of the donor) strongly affects
      posttransplantation hepatitis C virus-related disease progression. 4. Hepatitis C
      related disease progression is faster in patients who underwent transplantation
      in recent years as compared with those who underwent transplantation in earlier
      cohorts. The increasing age of the donor and the use of stronger
      immunosuppression may, in part, explain the worse outcomes seen in recent years.
      5. Additional host-related variables predictive of outcome include the
      immunogenetic background, the timing of recurrence, and the early histologic
      findings.

PMID- 14586895
TI  - The use of hepatitis C-infected grafts in liver transplantation.
AB  - 1. Liver grafts from hepatitis C virus (HCV)-infected deceased donors can be used
      safely in HCV-infected recipients. 2. Histological assessment of the graft before
      orthotopic liver transplantation (OLT) is advised. 3. Recipients of these grafts
      should give consent accordingly. 4. The course of HCV disease after OLT parallels
      that in patients who received noninfected organs.

PMID- 14586896
TI  - Living donor liver transplantation in patients with hepatitis C.
AB  - 1. Hepatitis C virus (HCV) is the most common indication for living donor liver
      transplantation (LDLT). 2. Preliminary evidence suggests that HCV may occur
      earlier and may be more severe in LDLT recipients. However, current data is
      inconclusive relative to the impact of recurrent HCV on patient and graft
      survival in LDLT recipients. 3. Potential mechanisms for differences in severity
      of HCV in LDLT recipients are discussed. 4. LDLT remains a viable treatment
      option for selected patients with HCV.

PMID- 14586897
TI  - Liver biopsy, viral kinetics, and the impact of viremia on severity of hepatitis
      C virus recurrence.
AB  - 1. Nearly all recipients who are chronically infected with hepatitis C virus
      (HCV) at the time of liver transplantation will have HCV RNA detectable
      postoperatively. 2. HCV replication can begin as early as the first postoperative
      week. 3. HCV levels fall significantly during the anhepatic phase of liver
      transplantation and continue to fall during the first 12-24 hours
      posttransplantation. 4. Serum HCV RNA levels typically increase rapidly from the
      second week posttransplantation and peak by the fourth postoperative month. HCV
      RNA levels at one year posttransplantation are 10-20 fold greater than
      pretransplant levels. 5. Corticosteroid treatment for acute cellular rejection is
      associated with large increases in HCV RNA levels. 6. HCV RNA levels do not
      appear to vary with choice of calcineurin inhibitor. 7. Early HCV RNA levels are
      predictive of subsequent histological severity of recurrence. 8. A correlation
      between early levels of viremia and subsequent allograft injury suggests that
      initiation of antiviral therapy early in the posttransplant course might be
      desirable.

PMID- 14586898
TI  - The role of immunosuppression in recurrence of hepatitis C.
AB  - 1. Recurrent hepatitis C is an increasing problem posttransplantation. 2. It is
      difficult to determine histologically if alloimmunity, i.e., rejection, is also
      plays a role in posttransplantation hepatitis C. 3. Change in the degree of
      immunosuppression, rather than the absolute amount of immunosuppression, is bad
      for HCV-infected recipients. 4. Corticosteroid boluses are bad for HCV-infected
      recipients.

PMID- 14586899
TI  - Retransplantation for recurrent hepatitis C: positive aspects.
AB  - 1. The prevalence of retransplantation for hepatitis C (HCV) patients is stable
      (around 40%). 2. Survival models to predict outcome of retransplantation do not
      show that HCV is an independent variable with poor outcomes. 3. Using Model for
      End-Stage Liver Disease (MELD) scores from the United Network for Organ Sharing
      (UNOS) database from 1996-2002, retransplantation for HCV had similar outcomes to
      other causes of retransplantation. 4. Poorer outcomes were noted for
      retransplantation with MELD scores greater than 25. 5. Minimal survival
      thresholds need to be developed for retransplantation for all causes of
      retransplantation.

PMID- 14586900
TI  - Retransplantation for recurrent hepatitis C: the argument against.
AB  - 1. Cirrhosis from chronic hepatitis C is the most common indication for liver
      grafting today. The course of hepatitis C is accelerated after liver
      transplantation, and no current therapy reliably prevents or arrests it. 2. It is
      anticipated that 20% or more of hepatitis C virus-positive transplant recipients
      will develop allograft cirrhosis, and the only solution will be
      retransplantation. 3. Results of retransplantation are inferior to primary
      transplantation. 4. Recipient risk factors that adversely affect mortality after
      repeated liver grafting include age older than 50 years, renal insufficiency, and
      severity of hyperbilirubinemia. When present, they reduce survival after
      retransplantation to approximately 40% or less. 5. Retransplantation on a large
      scale for recurrent hepatitis C is problematic from the perspectives of outcome,
      resource utilization, and fairness to candidates awaiting primary grafts.

PMID- 14586901
TI  - The clinical and immunologic impact of using interferon and ribavirin in the
      immunosuppressed host.
AB  - 1. Allograft infection with hepatitis C virus (HCV) in immunosuppressed adults
      results in decreased allograft and patient survival. 2. Risk factors for
      accelerated progression of hepatitis C related to immunosuppression include
      treated episodes of acute cellular rejection (ACR), pulse therapy with
      methylprednisolone, and use of OKT3. 3. Both interferon alfa (IFN-alpha) and
      ribavirin (RVN) show antiviral actions against HCV and stimulate innate and
      adaptive immunity to increase cytolysis and polarize T helper subtype 1 (T(H)1)
      responses. In addition, IFN-alpha inhibits fibrogenesis in the liver. 4. Both IFN
      alpha and RVN have been studied in immunosuppressed liver transplant recipients
      as prophylaxis or treatment of established hepatitis C to reduce allograft
      failure and patient mortality. Reported protocols include monotherapies with RVN,
      standard IFN-alpha, and pegylated IFN-alpha and combination therapies using RVN
      and either standard IFN-alpha or pegylated IFN-alpha. 5. The clinical impact of
      using IFN-alpha and RVN in highly selected immunosuppressed patients varied among
      studies. Combination therapy with standard IFN-alpha and RVN resulted in the
      greatest sustained biochemical and virological responses. However, no therapy
      prevented progression of acute cholestatic hepatitis C despite evidence of
      virological responses. Substantial proportions of patients developed adverse
      events requiring dose reduction or discontinuation that compromised efficacy. RVN
      monotherapy was not only virologically ineffective, but may have stimulated
      hepatic fibrosis. Current data regarding monotherapy or combination therapy with
      pegylated IFN-alpha are limited, but encouraging. 6. Despite potent
      immunostimulatory actions of both IFN-alpha and RVN that enhance natural killer,
      T(H)1, their use did not significantly increase the incidence of ACR. 7.
      Additional studies are needed to resolve the controversy over prophylaxis versus
      treatment of established disease and the potential utility of low-dose
      maintenance IFN-alpha therapy to retard fibrogenesis without clearing HCV. 8.
      After new, less toxic, and more potent antiviral agents become available, they
      should be tested immediately in patients with hepatitis C post-liver
      transplantation.

PMID- 14586902
TI  - Treatment of patients with hepatitis C virus on the waiting list.
AB  - 1. Over 90% of patients with hepatitis C on the waiting list might be candidates
      for therapy with interferon plus ribavirin. 2. One must exercise caution in the
      treatment of these patients. Those with Child-Turcotte-Pugh score >11 or Model
      for End-Stage Liver Disease score >25 should be excluded from treatment. 3.
      Sustained virologic response (hepatitis C virus RNA-negative) is mainly dependent
      on viral genotype, with 50% of genotype 2 and 3 patients achieving sustained
      virologic response. 4. The ability to achieve sustained virologic response in
      genotype 1 patients is dependent on dose and duration of treatment. 5. Patients
      rendered hepatitis C virus RNA-negative pretransplantation may not experience
      posttransplantation recurrence.

PMID- 14586903
TI  - Prophylactic and preemptive therapies for hepatitis C virus-infected patients
      undergoing liver transplantation.
AB  - 1. Preclinical data from chimpanzees and studies in hepatitis B virus/hepatitis C
      virus (HCV) coinfected transplant recipients suggest prophylactic HCV antibody
      therapy may have a role in the prevention of HCV recurrence. 2. There are
      insufficient data available to evaluate the efficacy of this therapeutic
      approach. A small study found no benefit. Other ongoing studies using alternative
      antibody preparations and more intensive dosing schedules are underway. 3.
      Preemptive antiviral therapy, started within the first 4 weeks
      posttransplantation and prior to the onset of clinical signs and symptoms, is
      effective in some patients (5-33%) and is not associated with an increased risk
      of acute rejection. Tolerability of antiviral agents in the early
      posttransplantation period may be a factor limiting treatment efficacy. 4. It is
      unclear whether the preemptive antiviral treatment is superior to delaying
      treatment until recurrent disease is present and controlled trials addressing
      this issue are needed.

PMID- 14586904
TI  - Treatment of hepatitis C virus infection in the allograft.
AB  - 1. Recurrence of hepatitis C virus (HCV) in the graft is associated with a
      reduced quality of life and worse graft survival. 2. Pretransplantation, the
      severity of HCV recurrence may be reduced by reducing the pretransplantation
      load, by avoiding the use of organs from older donors, and by reducing the
      ischemic times. The effect of split livers on recurrence rates is uncertain. 3.
      The optimal immunosuppression regime has not been established but a heavy
      induction regime and treatment for acute rejection are associated with more viral
      replication and more graft damage. 4. Presently, there is no convincing evidence
      for preemptive treatment of HCV. 5. There are many studies on the effect of
      interferon with and without ribavirin for the treatment of HCV hepatitis.
      However, few are prospective, randomized, and controlled. 6. The current best
      treatment is with pegylated interferon and ribavirin; the dose and duration of
      treatment need to be established. Side-effects of treatment are common and
      reduction/withdrawal is frequent, but the regime is cost-effective. 7. The role
      of newer treatments remains to be established.

PMID- 14586905
TI  - How can we identify better those with recurrent hepatitis C who will respond to
      therapy? What are the optimal treatment regimen and treatment duration?
AB  - 1. Treatment responses are lower in immune compromised patients such as those
      with hepatitis C virus (HCV) disease following liver transplantation than in
      immune competent patients with HCV disease. 2. Predictors of nonresponse,
      extrapolated from studies of immune competent patients, are overly represented in
      liver transplantation patients (high levels of HCV RNA and genotype 1 infection).
      3. Tolerability of peginterferon plus ribavirin therapy is lower in transplant
      patients than in immune competent patients with HCV disease, in part because of a
      baseline renal insufficiency that increases the likelihood of ribavirin
      associated anemia. 4. Clear recommendations regarding optimal treatment regimens
      for patients with posttransplantation HCV disease are problematic since there are
      few prospective, randomized, controlled trials that evaluated different treatment
      regimens. 5. If treatment is undertaken, baseline creatinine clearance should be
      measured and patients should be started on a dose of ribavirin of 400mg bid, or
      lower if renal function is impaired. 6. Tolerated peginterferon doses may be
      somewhat lower than for the standard immune competent patients. It is likely that
      lower doses will not greatly compromise response (1.0 ug/kg/week for
      peginterferon alfa 2b and 135 ug/week for peginterferon alfa 2a). 7. Optimal
      treatment duration is unknown. In patients with an on-treatment response, at
      least 12 months of therapy is recommended. 8. More potent drugs with fewer
      toxicities are needed for patients with progressive posttransplantation liver
      disease.

PMID- 14586906
TI  - New approaches and therapeutic modalities for the prevention and treatment of
      recurrent HCV after liver transplantation.
AB  - 1. The currently available interferon-based therapeutic regimens are not optimal
      for the treatment of recurrent hepatitis C after liver transplantation. 2. Many
      patients have contraindications to use of the drugs, dose reductions limit
      exposure to effective doses in most patients, and the therapy is labor intensive
      for the transplantation staff. 3. Better strategies are needed to control
      hepatitis C virus infection in the transplantation setting. Aggressive treatment
      of infected patients before they develop cirrhosis or hepatic decompensation may
      eliminate the need for transplantation in some and reduce the chance for
      posttransplantation recurrence in others. 4. Infusions of neutralizing antibodies
      or short courses of therapy with potent antiviral drugs in the
      peritransplantation period may reduce the chance of infection of the graft. 5.
      New antiviral strategies, including use of oligonucleotides and viral enzyme
      inhibitors, may prove useful in the future, but these agents are just beginning
      to be tested in clinical trials in human beings.

PMID- 14586907
TI  - Access to health care services among people with chronic or disabling conditions:
      patterns and predictors.
AB  - OBJECTIVE: To examine patterns of access to a variety of specific health care
      services among people with chronic or disabling conditions, focusing on factors
      that predict access to services. DESIGN: National survey of 800 adults with
      cerebral palsy (CP), multiple sclerosis (MS), spinal cord injury (SCI), or
      arthritis. SETTING: Respondents were surveyed in the general community.
      PARTICIPANTS: National convenience sample of adults with CP, MS, SCI, or
      arthritis. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Access to
      services from primary care doctors, services from specialists, rehabilitative
      services, assistive equipment, and prescription medications. Cross tabulations
      and logistic regression analyses were performed on survey data to examine
      patterns and predictors of access to health care services. RESULTS: Only half of
      all respondents received needed rehabilitative services. Respondents covered by
      fee-for-service health plans were more likely than those covered by managed care
      organizations to receive needed services from specialists. Respondents with the
      poorest health and with the lowest incomes were the least likely to receive all
      health services examined. CONCLUSIONS: People with chronic or disabling
      conditions often require a comprehensive array of health care services. Reform of
      the current health care payment and delivery structures is needed so that health
      care is more responsive to those with the greatest service needs.

PMID- 14586908
TI  - Two years later: a prospective long-term follow-up of a training intervention in
      geriatric patients with a history of severe falls.
AB  - OBJECTIVE: To study the long-term outcome of a physical training regimen of
      ambulant postward rehabilitation in community-dwelling geriatric patients with a
      history of injurious falls. DESIGN: Prospective 2-year follow-up of a randomized
      placebo-controlled intervention trial. SETTING: Postward rehabilitation in a
      geriatric hospital in Germany. PARTICIPANTS: Fifty-seven geriatric patients (mean
      age, 84.3+/-4.4 y) with a history of severe falls. INTERVENTION: Ambulatory
      training of strength, functional performance, and balance 3 times a week for 3
      months for 31 patients versus placebo activities for 26 patients. MAIN OUTCOME
      MEASURES: Strength, functional performance, fall-related psychologic parameters,
      and physical activity assessed by standardized protocols 2 years after the
      training intervention, compared with baseline results. RESULTS: Motor performance
      decreased substantially in both groups. As patients in the intervention group
      declined from significantly improved motor performance levels achieved in the
      initial training intervention, differences between the groups were still
      significant in most functional performances 2 years later. Functional decline was
      greater in persons who were institutionalized or being cared for by family
      members. Physical activity, which increased during the exercise intervention,
      returned to low baseline levels. CONCLUSIONS: Improved functional performance in
      the training group did not lead to an increased level of physical activity after
      training, which might have preserved the functional improvements. In mobility
      restricted, frail, geriatric patients such as our study population, training
      programs should continue to keep patients active and to prevent the decline in
      strength and functional performance that precedes loss of autonomy.

PMID- 14586909
TI  - Progressive resistance strengthening exercises after stroke: a single-blind
      randomized controlled trial.
AB  - OBJECTIVE: To determine the effectiveness of progressive resistance strengthening
      exercises to improve gross motor function and walking in patients receiving
      intensive rehabilitation after stroke. DESIGN: Randomized controlled trial.
      SETTING: Five inpatient rehabilitation programs affiliated with teaching
      hospitals. PARTICIPANTS: Inclusion criteria included less than 6 months
      poststroke and recovery of the leg stages 3 to 5 on the Chedoke-McMaster Stroke
      Assessment (CMSA). INTERVENTIONS: Both groups received conventional physical
      therapy programs. In addition, the experimental group performed 9 lower-extremity
      progressive resistance exercises 3 times a week for the duration of their stay,
      whereas the control group did the same exercises and for the same duration but
      without resistance. MAIN OUTCOME MEASURES: The Disability Inventory of the CMSA
      and the 2-minute walk test (2MWT) at baseline, 4 weeks, discharge, and 6 months
      after discharge. RESULTS: Over the length of stay, the rate of change in the
      Disability Inventory was.27 points per day in the experimental group and.29
      points per day in the control group; the between-group difference was -.02 points
      per day (95% confidence interval [CI], -.10 to.06; P=.62). At discharge, the rate
      of change in the 2MWT was -.01 m in the experimental group and.15m in the control
      group; the between-group difference was -.16 m (95% CI, -.37 to.05; P=.14).
      CONCLUSIONS: Progressive resistance strengthening exercises as applied in our
      study were not effective when compared with the same exercises given without
      resistance.

PMID- 14586910
TI  - The relationship between therapy intensity and rehabilitative outcomes after
      traumatic brain injury: a multicenter analysis.
AB  - OBJECTIVES: To identify factors relating to the intensity of rehabilitation
      services received and to ascertain the relation between injury outcomes,
      demographics, types of therapy, and the intensity of rehabilitation services
      provided. DESIGN: A multicenter, prospective, nonrandomized study with inpatient
      rehabilitation data collected between 1989 and 1996. SETTING: Three medical
      centers in the federally sponsored Traumatic Brain Injury Model Systems. In each
      setting, the continuum of care includes emergency medical services, intensive and
      acute medical care, and inpatient rehabilitation. PARTICIPANTS: A total of 491
      consecutively enrolled patients with a mean age +/- standard deviation of 34.3+/
      15.88 years recruited from 3 medical centers. To be included in the study,
      patients must have been at least 16 years of age, have presented to the emergency
      department within 24 hours of injury, and have received acute care and inpatient
      rehabilitation. INTERVENTIONS: Patients received comprehensive medical care along
      with a combination of rehabilitative therapies, including physical, occupational,
      psychologic, and speech therapy. MAIN OUTCOME MEASURES: Therapy intensity; levels
      of functional independence, cognitive function, functional gain, and treatment
      efficiency, as indicated by the FIM instrument; rehabilitation length of stay
      (LOS); and charges. RESULTS: Age predicted the intensity of both psychologic
      (P<.001) and total therapy (P<.01) services. Acute care LOS was also a
      significant predictor of psychologic services (P<.01). Only admission motor FIM
      was relevant in predicting speech services intensity (P<.01). Therapy intensity
      was predictive of motor functioning at discharge (P<.001). However, therapy
      intensity did not predict cognitive gain (P<.05). CONCLUSIONS: This study is
      among the first multicenter efforts to examine the potential benefits of
      individual therapy services. Findings support assertions that increased therapy
      intensity, particularly physical and psychologic therapies, enhances functional
      outcomes.

PMID- 14586911
TI  - Outcome 3 to 5 years after moderate to severe traumatic brain injury.
AB  - OBJECTIVE: To investigate neuropsychologic, emotional, and functional status and
      quality of life (QOL) 3 to 5 years after moderate to severe traumatic brain
      injury (TBI). DESIGN: Observational cohort. SETTING: Level I trauma center.
      PARTICIPANTS: Consecutive adult admissions with TBI involving intracranial
      abnormalities, prospectively followed up for 3 to 5 years, with 80% follow-up.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Neuropsychologic
      functioning (Paced Auditory Serial Addition Test, California Verbal Learning
      Test), emotional status (Center for Epidemiologic Studies Depression Scale, Brief
      Symptom Inventory), functional status (Functional Status Examination, Glasgow
      Outcome Scale, Medical Outcomes Study 36-Item Short-Form Health Survey,
      employment), and perceived QOL. RESULTS: Significant functional limitations were
      observed in all areas. Recovery to preinjury levels ranged from 65% of cases in
      personal care to approximately 40% in cognitive competency, major activity, and
      leisure and recreation. Brain injury severity, measured by the modified
      Abbreviated Injury Scale, related to functional status and neuropsychologic
      functioning, but not to emotional or QOL measures. Length of impaired
      consciousness appeared to contribute to outcome more than did anatomic lesions.
      CONCLUSIONS: The results provide representative estimates of long-term morbidity
      in patients with TBI involving intracranial lesions. The magnitude of morbidity
      was high. Although direct costs of TBI have received the most attention, the long
      term consequences and their cost implications are much larger, unfold over time,
      and are borne by the survivors, their families, and the public subsidy system.

PMID- 14586912
TI  - Optimal outcomes obtained with body-weight support combined with treadmill
      training in stroke subjects.
AB  - OBJECTIVES: To identify stroke patients who are most likely to benefit from
      locomotor training with body-weight support (BWS), to determine the extent of
      carryover from treadmill training to overground locomotion, and to determine the
      variables that are most likely to influence the recovery of locomotion. DESIGN: A
      randomized clinical trial. SETTING: Inpatient rehabilitation hospital.
      PARTICIPANTS: Of 100 stroke subjects, 50 were randomized to receive locomotor
      training with BWS (BWS group), and 50 were randomized to receive locomotor
      training with full weight bearing (no-BWS group). The subjects were stratified
      according to their initial overground walking speed and endurance, initial
      treadmill speed and endurance, functional balance, motor recovery, side of the
      lesion, and age. INTERVENTION: Fifty subjects were trained to walk on a treadmill
      with up to 40% of their body weight supported by a BWS system with an overhead
      harness (BWS group), and 50 subjects were trained to walk while bearing their
      full weight (no-BWS group). MAIN OUTCOME MEASURES: Clinical outcome measures
      included overground walking speed and endurance, functional balance, and motor
      recovery. The effect of confounding variables such as age, comorbidity, and
      depression on locomotor outcome was also investigated. RESULTS: After 6 weeks of
      locomotor training, the BWS group scored significantly higher in all clinical
      outcomes. When the subjects were stratified according to their initial overground
      walking speed, endurance, balance, and motor recovery, a significant statistical
      difference in gait and balance dysfunction of all outcomes occurred in the more
      severely impaired subjects. An important transfer from treadmill speed to
      overground walking speed was observed in subjects in the BWS group. Finally, a
      significantly greater effect was observed in older subjects (65-85y) in the BWS
      group. CONCLUSIONS: Retraining gait in severely impaired stroke subjects with a
      percentage of their body weight supported resulted in better walking and postural
      abilities than did gait training in patients bearing their full weight. It
      appears that subjects with greater gait impairments benefited the most from
      training with BWS, as did the older patients with stroke. There is evidence of
      transfer from treadmill training to overground locomotion.

PMID- 14586913
TI  - Pelvic movement and interface pressure distribution during manual wheelchair
      propulsion.
AB  - OBJECTIVE: To investigate the movement of the ischial tuberosities and the
      redistribution of interface pressure during manual wheelchair propulsion. DESIGN:
      Measurement of ischial tuberosity positions and comparison with corresponding
      position of the zones of peak pressure by using independent samples t tests.
      Analysis of variance was used to compare peak and average pressures under static
      and dynamic conditions. SETTING: Human locomotion laboratory. PARTICIPANTS: Ten
      subjects with spinal cord injury (SCI) and 10 individuals with no disabilities.
      INTERVENTIONS: Manual wheelchair propulsion on a stationary wheelchair ergometer
      at the subject's maximum propulsion speed. MAIN OUTCOME MEASURES: Seat interface
      pressure and the 3-dimensional position of the pelvis were measured with a
      pressure mat and an optical motion analysis system. RESULTS: During wheelchair
      sprinting, the ischia were located at 19.2+/-11.7 mm behind the corresponding
      peak pressure locations. The anteroposterior rocking of the pelvis was 11.2
      degrees and 5.2 degrees for the normal and SCI group, respectively. The average
      interface pressure over the ischial tuberosity area was lower under dynamic
      conditions. It was also observed in the SCI group that there was a concentration
      of high-pressure gradients around the peak pressure areas of the buttock during
      dynamic propulsion. CONCLUSION: Peak pressure locations did not concur exactly
      with the ischial tuberosities during propulsion. The movements of the ischial
      bone and the cyclic loading imposed on the tissue underneath the ischial
      tuberosities during dynamic conditions may have implications for the etiology of
      decubitus ulcers.

PMID- 14586914
TI  - Shoulder kinematics in subjects with frozen shoulder.
AB  - OBJECTIVES: To describe 3-dimensional humeral motion in subjects with frozen
      shoulder and to determine whether a consistent capsular pattern of restriction
      was present. DESIGN: Descriptive study including repeated measurements of
      shoulder kinematics. SETTING: Motion-analysis laboratory. PARTICIPANTS: Ten (9
      women, 1 man) volunteers with a diagnosis of idiopathic adhesive capsulitis and
      10 (9 women, 1 man) subjects with asymptomatic shoulders as comparison subjects.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Electromagnetic tracking
      sensors monitored the 3-dimensional position of the trunk, scapula, and humerus
      throughout active shoulder motions. Peak humeral positions relative to the trunk
      and scapula were determined for shoulder flexion, abduction, scapular plane
      abduction, external rotation (ER), and internal rotation (IR). Descriptive
      statistics (means, standard deviations, percentage of normal) were calculated and
      capsular patterns described. RESULTS: For humeral position relative to the trunk,
      subjects' mean peak motion was as follows: abduction, 98.4 degrees; ER at the
      side, 4.5 degrees; ER with the arm abducted, 33.5 degrees; flexion, 116.9
      degrees; IR at the side, 54.3 degrees; IR with the arm abducted, 17.8 degrees;
      and scapular plane abduction, 113.4 degrees. For humeral position relative to the
      scapula, subjects' mean peak motion was as follows: abduction, 46.4 degrees; ER
      at the side, 34.7 degrees; ER with the arm abducted, 45.3 degrees; flexion, 70.5
      degrees; IR at the side, 10.3 degrees; IR with the arm abducted, -6.4 degrees;
      and scapular plane abduction, 61.7 degrees. CONCLUSIONS: Symptomatic subjects
      demonstrated substantial kinematic deficits during humeral range of motion. No
      single capsular pattern emerged.

PMID- 14586915
TI  - Shoulder pain, range of motion, and functional motor skills after acute
      tetraplegia.
AB  - OBJECTIVES: To investigate (1) the prevalence and course of shoulder pain in
      acute tetraplegia and (2) its relationship with range of motion (ROM) and
      function and any associated risk factors. DESIGN: A longitudinal prospective
      study. SETTING: Spinal injury unit in an Australian hospital. PARTICIPANTS:
      Inpatients with acute tetraplegia. INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURES: Demographics, pain intensity, shoulder ROM, and functional motor
      skills. RESULTS: The prevalence of pain during rehabilitation was 85%. Risk
      factors associated with pain during rehabilitation included age less than 30
      years or more than 50 years (F=8.892, P=.064), admission motor level at C2-5
      (F=5.833, P=.016), admission sensory level at C2-5 (F=7.543, P=.006), lower left
      upper limb (P=.005; 95% confidence interval [CI], -14.74 to -2.86) and total
      American Spinal Injury Association motor scores (P=.009; 95% CI, -29.53 to 
      4.67), and a shorter duration of bedrest (F=5.794, P=.055). Subjects with pain
      lost ROM in left abduction (P=.038; 95% CI, -25.9 to -0.9) and right abduction
      (P=.05; 95% CI, -30 to 9.3). No relationship existed between shoulder pain and
      functional motor skills on discharge. CONCLUSION: Shoulder pain is common in
      acute tetraplegia and is associated with loss of shoulder ROM. Risk factors
      identified include age, injury level, and duration of bedrest. Areas for further
      study are identified.

PMID- 14586917
TI  - Long-term mental health of women after a first acute myocardial infarction.
AB  - OBJECTIVES: To compare the long-term psychologic well-being and psychologic
      distress, after a first acute myocardial infarction (AMI), of women with those of
      men and those of a normative community sample of women and to examine the
      relation of sociodemographic, medical, and psychologic variables to the long-term
      psychologic well-being and psychologic distress of women. DESIGN: Longitudinal
      study. SETTING: Eight medical centers in central Israel. PARTICIPANTS: Sixty-two
      women (age range, 30-65y) with documented first AMI. INTERVENTIONS:
      Sociodemographic, medical, and psychologic data were collected before hospital
      discharge (T1). Psychologic well-being and psychologic distress were assessed 5
      years after AMI (T2) with the Mental Health Inventory. MAIN OUTCOME MEASURES:
      Hierarchical regression was used to examine the relations among the outcome
      variables, psychologic well-being, and psychologic distress at T2 and the
      predictors, sociodemographic, medical, and psychologic variables at T1. RESULTS:
      Women had less long-term psychologic well-being and more psychologic distress
      after AMI than did men or the normative sample of women. Depression and
      concomitant medical problems were related to women's psychologic well-being;
      depression alone was related to their long-term psychologic distress.
      CONCLUSIONS: Women with an AMI are more likely than men to have reduced
      psychologic well-being and increased psychologic distress. In addition,
      diminished mental health was related to medical and psychologic pathogenic
      factors.

PMID- 14586916
TI  - A treadmill and overground walking program improves walking in persons residing
      in the community after stroke: a placebo-controlled, randomized trial.
AB  - OBJECTIVE: To evaluate the effectiveness of a treadmill and overground walking
      program in reducing the disability and handicap associated with poor walking
      performance after stroke. DESIGN: Randomized, placebo-controlled clinical trial
      with a 3-month follow-up. SETTING: General community. PARTICIPANTS: A volunteer
      sample of 29 ambulatory individuals (less 2 dropouts) who were living in the
      community after having suffered a stroke more than 6 months previously.
      INTERVENTIONS: The experimental group participated in a 30-minute treadmill and
      overground walking program, 3 times a week for 4 weeks. The control group
      received a placebo consisting of a low-intensity, home exercise program and
      regular telephone contact. MAIN OUTCOME MEASURES: Walking speed (over 10 m),
      walking capacity (distance over 6 min), and handicap (stroke-adapted 30-item
      version of the Sickness Impact Profile) measured by a blinded assessor. RESULTS:
      The 4-week treadmill and overground walking program significantly increased
      walking speed (P=.02) and walking capacity (P<.001), but did not decrease
      handicap (P=.85) compared with the placebo program. These gains were largely
      maintained 3 months after the cessation of training (P</=.05). CONCLUSIONS: The
      treadmill and overground walking program was effective in improving walking in
      persons residing in the community after stroke. This suggests that the routine
      provision of accessible, long-term, community-based walking programs would be
      beneficial in reducing disability after stroke.

PMID- 14586918
TI  - Cognitive recovery after stroke: a 2-year follow-up.
AB  - OBJECTIVES: To determine (1) whether long-term improvement of cognitive function
      takes place after stroke and (2) which clinical factors influence cognitive
      recovery. DESIGN: Cohort study with patients who were assessed at 2.3 and 27.7
      months after stroke. SETTING: Home-based stroke patients. PARTICIPANTS: From a
      group of 229 stroke patients, 92 were approached to participate. Sixty-five (43
      men, 22 women; mean age, 56.4y) agreed, and they were neuropsychologically
      assessed at 72.2 days after stroke. A group of 33 controls (12 men, 21 women;
      mean age, 52.4y) was used as a reference sample. INTERVENTIONS: Not applicable.
      MAIN OUTCOME MEASURES: Orientation, memory, attention, visuospatial,
      visuoconstructive, language, and arithmetic abilities were assessed with an
      extensive neuropsychologic test battery. RESULTS: Significant improvements across
      time were noted for all cognitive domains. The biggest improvement was found in
      the attentional domain; the least, in the memory domain. In addition, a small
      subset of patients accounted for the significant improvement in all cognitive
      domains; most patients showed no improvement or declined. Factors influencing
      recovery were side of the stroke and incidence of lowered consciousness on
      admission. Patients with right-side brain damage performed better than those with
      left-side brain damage and showed more improvement over time. Patients with
      lowered consciousness on admission performed worse than patients without lowered
      consciousness. No significant effect was found for gender, type of stroke,
      cortical versus subcortical lesions, having 1 stroke or multiple strokes, or the
      interval between the stroke and the neuropsychologic assessment. CONCLUSION:
      There was room for improvement in all cognitive domains, although this
      improvement was gained by only a small number of patients. Hence, most patients
      must cope with serious permanent cognitive decline after stroke.

PMID- 14586919
TI  - Effect of sensory discrimination training on structure and function in patients
      with focal hand dystonia: a case series.
AB  - OBJECTIVE: To measure the effects of sensorimotor training based on the
      principles of neuroplasticity for patients with focal hand dystonia. DESIGN: Case
      series of 3 subjects with focal hand dystonia of the left hand, compared with age
      matched normative controls. SETTING: Outpatient clinic. PARTICIPANTS: Three
      consecutive clinic patients-musicians with focal hand dystonia-who described a
      history of repetitive practice and performance (2 women; ages, 23 y and 35 y; 1
      man; age, 24 y). INTERVENTION: Subjects were asked to stop performing the tasks
      that caused the abnormal movements, to participate in a wellness program
      (aerobics, postural exercises, stress free hand use), and to carry out
      supervised, attended, individualized, repetitive sensorimotor training activities
      at least once week for 12 weeks and reinforced daily at home. MAIN OUTCOME
      MEASURES: Standard tests documenting somatosensory hand representation, target
      specific hand control, and clinical function. RESULTS: On the affected side, the
      3 subjects improved an average of 86.8% on somatosensory hand representation,
      117% on target-specific performance, 23.9% on fine motor skills, 22.7% on sensory
      discrimination, 31.9% on musculoskeletal skills, and 32.3% on independence. All 3
      subjects improved 10% or more on 90% of the subtests with 20% improvement on 50%
      of the subtests. CONCLUSION: Individuals with focal hand dystonia who have a
      history of repetitive hand use can improve cortical somatosensory responses and
      clinical motor function after individualized sensorimotor training consistent
      with the principles of neural adaptation.

PMID- 14586920
TI  - Increases in local pressure pain thresholds after muscle exertion in women with
      chronic shoulder pain.
AB  - OBJECTIVE: To examine the relation between muscular tenderness and local muscular
      fatigue. DESIGN: Before-after trial, measuring pressure pain thresholds and signs
      of local muscular fatigue by using surface electromyography before, after, 10
      minutes after, and 20 minutes after intervention. SETTING: University
      rehabilitation department in Sweden. PARTICIPANTS: Nineteen female hospital
      cleaners with unilateral chronic shoulder pain for 1 year. No previous trauma,
      surgery, or signs of systemic or neurologic disease. INTERVENTION: Static
      abduction endurance test with submaximal unilateral activation of the trapezius
      and deltoid muscles. MAIN OUTCOME MEASURES: Pressure pain thresholds and
      electromyographic fatigue parameters (root mean square [RMS]; mean power
      frequency [MPF]). RESULTS: Mean normalized pressure pain threshold values
      increased significantly (95% confidence interval [CI]) and lasted for 20 minutes:
      in the trapezius, threshold values increased to 115% to 120% (95% CI, 100%-140%;
      P=.04-.05); and in the deltoid, the threshold increased to 112% to 115% (95% CI,
      100%-130%; P=.02-.05). Development of significant electromyographically defined
      fatigue was seen: in the trapezius, the RMS increased to 130% (95% CI, 119%
      141%), and in the deltoid, the MPF decreased to 78% (95% CI, 74%-82%), but
      normalized within 15 seconds to 10 minutes. CONCLUSION: Lasting bilateral
      increases in pressure pain thresholds but transient local muscular fatigue were
      seen after a unilateral static endurance test. The sensitivity of the sensory
      nervous system may change during a static muscle contraction and sometimes
      contributes to a localized sensation of numbness.

PMID- 14586921
TI  - Treatment of calcifying tendinitis of the shoulder by acetic acid iontophoresis:
      a double-blind randomized controlled trial.
AB  - OBJECTIVE: To assess the effects of acetic acid iontophoresis on the treatment of
      calcifying tendinitis of the shoulder. DESIGN: Double-blind randomized controlled
      trial. SETTING: Ambulatory academic hospital in Quebec, Canada. PARTICIPANTS:
      Thirty-six subjects with a calcifying tendinitis of the shoulder. INTERVENTIONS:
      Subjects were randomized into 1 of 2 groups: physiotherapy during 6 weeks (10
      sessions) plus acetic acid iontophoresis for the treatment group (n=18) and sham
      acetic acid iontophoresis for the control group (n=18). MAIN OUTCOME MEASURES:
      The Shoulder Pain and Disability Index (SPADI), shoulder range of motion (ROM);
      and radiologic evaluation of shoulder calcifications. RESULTS: Nine patients
      dropped out, leaving 27 assessable subjects for analysis. Interim analysis showed
      that, in both groups, treatment led to improvement, as measured by the SPADI
      score (P=.004), ROM of the shoulder for abduction (P<.001), internal rotation
      (P=.001), external rotation (P<.001), and the mean number of calcifications per
      subject (P=.010). Although no formal significant intervention effects (P=.13)
      were found for the primary endpoint (SPADI), exploratory analyses suggest a
      greater improvement in the treatment group (P=.001) than in the control group
      (P=.33). CONCLUSIONS: Despite a trend toward greater improvement in the SPADI
      score in the treatment group, the use of acetic acid iontophoresis and
      physiotherapy for the treatment of calcifying tendinitis of the shoulder did not
      result in better clinical and radiologic effects than those observed in subjects
      treated by physiotherapyalone.

PMID- 14586922
TI  - Reliability of the dynamic gait index in people with vestibular disorders.
AB  - OBJECTIVE: To examine the interrater reliability of the Dynamic Gait Index (DGI)
      when used with patients with vestibular disorders and with previously published
      instructions. DESIGN: Correlational study. SETTING: Outpatient physical therapy
      clinic. PARTICIPANTS: Subjects included 30 patients (age range, 27-88y) with
      vestibular disorders, who were referred for vestibular rehabilitation.
      INTERVENTIONS: Subjects' performance on the DGI was concurrently rated by 2
      physical therapists experienced in vestibular rehabilitation to determine
      interrater reliability. MAIN OUTCOME MEASURES: Percentage agreement, kappa
      statistics, and the ratio of subject variability to total variability were
      calculated for individual DGI items. Kappa statistics for individual items were
      averaged to yield a composite kappa score of the DGI. Total DGI scores were
      evaluated for interrater reliability by using the Spearman rank-order correlation
      coefficient. RESULTS: Interrater reliability of individual DGI items varied from
      poor to excellent based on kappa values (kappa range,.35-1.00). Composite kappa
      values showed good overall interrater reliability (kappa=.64) of total DGI
      scores. The Spearman rho demonstrated excellent correlation (r=.95) between total
      DGI scores given concurrently by the 2 raters. CONCLUSION: DGI total scores,
      administered by using the published instructions, showed moderate interrater
      reliability with subjects with vestibular disorders. The DGI should be used with
      caution in this population at this time, because of the lack of strong
      reliability.

PMID- 14586923
TI  - Muscle mass, isokinetic torque, and functional capacity in women with
      osteoarthritis of the knee.
AB  - OBJECTIVES: To investigate the relations between cross-sectional area and
      concentric and eccentric torques in the quadriceps and hamstring muscles and to
      determine how functional capacity relates to pain, muscle mass, and concentric
      and eccentric knee torques in women who have bilateral osteoarthritis (OA) of the
      knee. DESIGN: Randomized, descriptive study. SETTING: A university exercise
      physiology laboratory in Turkey. PARTICIPANTS: Eighteen women with bilateral knee
      OA (grades 2 or 3) graded radiographically. INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURES: Selected functional tests included the 15-m walk, rising from a
      chair, descending stairs, and stair climbing. Pain during the functional tests
      was subjectively measured on an 11-point scale (range, 0-10). Concentric and
      eccentric torques of the quadriceps and hamstring muscles were measured by
      isokinetic dynamometry with angular velocities of 60 degrees, 120 degrees, and
      180 degrees /s; cross-sectional areas of the quadriceps and hamstring muscles
      were measured by computed tomography. RESULTS: Eccentric torque was significantly
      (P range, <.05 to.001) greater than concentric torque for the quadriceps (range,
      16%-100%) and hamstring (range, 50%-158%) muscles at all angular velocities.
      Torque-velocity curves for concentric and eccentric contractions were almost
      identical to those found in healthy young and elderly people. According to r(2)
      values, cross-sectional area of the quadriceps and hamstring muscles explained
      24% to 61% (r(2) range,.24-.61) and 38% to 51% (r(2) range,.38-.51) of the
      variations in concentric and eccentric peak torques, respectively. Very small to
      moderate correlations (.01-.75) were observed among torque at any velocity and
      the variables of functional capacity and pain. For stair-climbing times, the best
      predictor variable was the eccentric hamstring to concentric quadriceps torque
      ratio. For stair descending, it was the concentric hamstring to eccentric
      quadriceps torque ratios. These torque ratios explained 81% (r(2)=.81) and 61%
      (r(2)=.61) of the variations, respectively. CONCLUSIONS: The findings in a
      patient group with bilateral OA of the knee showed that (1) eccentric torque is
      greater than concentric torque in knee muscles; (2) the correlation coefficients
      (r) between concentric and eccentric torques at different velocities (r range,.63
      .86), but not between reciprocal torque ratios (r range,.02-.69), are good; (3)
      cross-sectional area cannot be considered as a single predictor of peak torque
      for either quadriceps or hamstring muscles; and (4) the variation in descending
      stairs and stair-climbing capacities can be explained by the reciprocal torque
      ratios of knee muscles.

PMID- 14586924
TI  - The efficacy of traction for back pain: a systematic review of randomized
      controlled trials.
AB  - OBJECTIVE: To assess the efficacy of traction for patients with low back pain
      (LBP) with or without radiating pain, taking into account the clinical technique
      or parameters used. DATA SOURCES: A computer-aided search of MEDLINE, CINAHL,
      AMED, and the Cochrane Collaboration was conducted for randomized controlled
      trials (RCTs) in the English language, from 1966 to December 2001. STUDY
      SELECTION: RCTs were included if: participants were over the age of 18 years,
      with LBP with or without radiating pain; the intervention group received traction
      as the main or sole treatment; the comparison group received sham traction or
      another conservative treatment; and the study used 1 of 4 primary outcome
      measures. DATA EXTRACTION: The study was conducted in 2 strands. Strand 1
      assessed methodologic quality using a specific criteria list recommended by the
      Cochrane Back Review Group. The strength of the evidence was then rated using the
      Agency for Health Care Policy and Research system. Strand 2 applied further
      inclusion criteria based on recommended clinical parameters. One reviewer
      conducted the selection and data extraction. DATA SYNTHESIS: Strand 1: 1 study
      scored 9 points (maximum score, 10 points); the other 12 scored between 0 and 3
      points, indicating that most were of poor quality. Nine studies reported negative
      findings, but only 1 study was of a high quality. Three studies reported positive
      findings and 1 study was inconclusive. Strand 2: only 4 trials having low
      methodologic quality were included, 2 of which reported negative findings, and 2
      positive findings. CONCLUSION: The evidence for the use of traction in LBP
      remains inconclusive because of the continued lack of methodologic rigor and the
      limited application of clinical parameters as used in clinical practice. Further
      trials, which give attention to these areas, are needed before any firm
      conclusions and recommendations may be made.

PMID- 14586925
TI  - De Quervain's tenosynovitis in patients with lymphedema: a report of 2 cases with
      management approach.
AB  - De Quervain's tenosynovitis is a tendonitis of the abductor pollicis longus and
      extensor pollicis brevis tendons. It commonly occurs as a result of overuse and
      is often seen in patients who perform repetitive activities. The occurrence of de
      Quervain's tenosynovitis in lymphedema has not been reported, nor has the
      management of de Quervain's tenosynovitis been discussed in the literature for
      patients whose lymphedema results from cancer or other disorders. Musculoskeletal
      conditions in lymphedema patients often require special considerations because
      these patients are more susceptible to infections and other complications. We
      describe the rehabilitation management of de Quervain's tenosynovitis in 2
      patients with lymphedema secondary to breast carcinoma. Both patients responded
      to conservative management with a good clinical outcome. We conclude that a
      conservative initial management approach consisting of the continued wear of a
      compression garment, the fabrication of a custom-made thumb spica, occupational
      therapy with an emphasis on tendon gliding exercises, and prescription of a
      nonsteroidal anti-inflammatory drug is effective and safe.

PMID- 14586926
TI  - Efficacy of therapeutic ultrasound treatment of a meniscus tear in a severely
      disabled patient: a case report.
AB  - This report focuses on diagnosis and management of a meniscus tear of unknown
      etiology in a functionally impaired patient. The patient was a 21-year-old man
      diagnosed with viral meningoencephalitis and postvaccinal central pontine
      myelinolysis, who experienced respiratory failure and required prolonged
      mechanical ventilation. He was in a comatose state for approximately 1.5 months.
      He presented to our facility 3 weeks after coma complaining of left knee pain and
      limited range of motion (ROM). Diagnostic workup, including magnetic resonance
      imaging, showed a grade II posterior horn medial meniscus tear and lateral tibial
      stress injury of the left knee. Management of the meniscus tear included the RICE
      protocol (rest, ice, compression, elevation), therapeutic ultrasound, and
      physical therapy. The patient responded extremely well to initial ultrasound
      therapy, with decreased pain and increased ROM of the left knee, which allowed
      him to make significant functional gains and to make overall progress in our
      comprehensive acute rehabilitation program. To date, nonoperative care of acute
      meniscal injury is commonly considered to be unsatisfactory; however, in this
      patient it led to rapid functional gains. Thus, therapeutic ultrasound may be a
      beneficial modality to decrease pain and increase ROM of the knee in an acutely
      torn meniscus, which, in turn, would likely promote good functional progress in
      any rehabilitation program.

PMID- 14586927
TI  - Effect of light finger touch on postural sway after lower-limb muscular fatigue.
AB  - OBJECTIVE: To investigate whether a light finger touch can compensate for the
      increased postural sway induced by lower-limb muscular fatigue. DESIGN: Before
      after trials. SETTING: General community. PARTICIPANTS: Nine healthy university
      students (mean age, 23.8+/-2.6y; mean body weight, 72.7+/-6.9 kg; mean height,
      177.2+/-7.5 cm). INTERVENTIONS: Participants stood with their feet together and
      eyes closed. They were asked to sway as little as possible in 4 conditions: no
      fatigue/no touch, no fatigue/touch, fatigue/no touch, and fatigue/touch. Calf
      muscle fatigue was induced by having participants stand on their toes until
      exhaustion. Touch conditions involved a gentle light touch with the right index
      finger on a nearby surface at waist height. MAIN OUTCOME MEASURES: Center of
      pressure displacements were recorded by using a force platform. RESULTS: Light
      finger touch resulted in decreased postural sway in the no-fatigue and fatigue
      conditions. Interestingly, this stabilizing effect was more accentuated in the
      fatigue condition. CONCLUSIONS: Results suggest that the contribution of the
      haptic cues from the finger for regulating postural sway increases after muscular
      fatigue. These findings could have implications in clinical and rehabilitative
      areas.

PMID- 14586928
TI  - Customized heel pads and soft orthotics to treat heel pain and plantar fasciitis.
AB  - We describe the design of a new cost-effective, comfortable orthotic designed to
      treat heel pain associated with plantar fasciitis. The heel pad is fabricated
      from a 4 degrees Sorbothane medial wedge with a customized insertion of low
      density Plastazote. The orthotic is medium-density Plastazote reinforced with
      cork in the medial longitudinal arch. One pair of orthotics takes less than 1
      hour to make. Pilot data were collected retrospectively to evaluate the efficacy
      of the orthotic for reducing pain. Ten clients at a hand and foot orthotic clinic
      with a mean age of 71+/-9.1 years and with unilateral or bilateral heel pain
      associated with plantar fasciitis were provided with customized heel pads and
      soft, molded orthotics at their initial visit. Pain levels were recorded with
      verbal and Likert-type scales. After 5 weeks of heel pad and orthotic use, all
      patients showed a reduction in pain, with the overall reduction being highly
      significant (P</=.0001). Customized heel pads and soft molded orthotics are an
      effective first-line treatment for the heel pain and loss of function associated
      with plantar fasciitis.

PMID- 14586999
TI  - Flow effects in balanced steady state free precession imaging.
AB  - An analysis of the effect of flow on 2D fully balanced steady state free
      precession (SSFP) imaging is presented. Transient and steady-state SSFP signal
      intensities in the presence of steady and pulsatile flow were simulated using a
      matrix formalism based on the Bloch equations. Various through-plane flow
      waveforms and rates were modeled numerically considering factors such as the
      excitation slice profile and both in- and out-flow effects. Phantom measurements
      in an experimental setup that allowed the assessment of SSFP signal properties as
      a function of frequency offset and flow rate demonstrated that the computer
      simulations provided a suitable description of the effects of flow in SSFP
      imaging. A volunteer scan was performed to provide in vivo validations. For
      accurate modeling of SSFP signal intensities it is crucial to include effects
      such as imperfect slice profiles and, more importantly, "out-of-slice"
      contributions to the signal. Both simulations and experiments show that there can
      be considerably large-frequency offset dependent-signal contributions from
      flowing spins that have already left the imaging slice but still add to the SSFP
      signal. Although spins leaving the slice do not experience additional RF
      excitation, gradient activity is not confined to the region of excitations and
      the balanced nature of the SSFP imaging gradients allows "out-of-slice"
      transverse magnetization to contribute to the total SSFP signal, effectively by
      broadening the slice thickness for flowing spins. This results in a frequency
      dependence of in-flow related signal enhancement and flow artifacts.

PMID- 14586998
TI  - Inflow effect correction in fast gradient-echo perfusion imaging.
AB  - The purposes of this study were to assess the extent of the inflow effect on
      signal intensity (SI) for fast gradient-recalled-echo (GRE) sequences used to
      observe first-pass perfusion, and to develop and validate a correction method for
      this effect. A phantom experiment with a flow apparatus was performed to
      determine SI as a function of Gd-DTPA concentration for various velocities.
      Subsequently a flow-sensitive calibration method was developed, and validated on
      bolus injections into an open-circuit flow apparatus and in vivo. It is shown
      that calibration methods based on static phantoms are not appropriate for
      accurate signal-to-concentration conversion in images affected by high flow. The
      flow-corrected calibration method presented here can be used to improve the
      accuracy and robustness of the arterial input function (AIF) determination for
      tissue perfusion quantification using MRI and contrast media.

PMID- 14587001
TI  - Dixon techniques in spiral trajectories with off-resonance correction: a new
      approach for fat signal suppression without spatial-spectral RF pulses.
AB  - Spiral imaging has recently gained acceptance in MR applications requiring rapid
      data acquisition. One of the main disadvantages of spiral imaging, however, is
      blurring artifacts that result from off-resonance effects. Spatial-spectral
      (SPSP) pulses are commonly used to suppress those spins that are chemically
      shifted from water and lead to off-resonance artifacts. However, SPSP pulses may
      produce nonuniform fat signal suppression or unwanted water signal suppression
      when applied in the presence of B(0) field inhomogeneities. Dixon techniques have
      been developed as methods for water-fat signal decomposition in rectilinear
      sampling schemes since they can produce unequivocal water-fat signal
      decomposition even in the presence of B(0) inhomogeneities. This article
      demonstrates that three-point and two-point Dixon techniques can be extended to
      conventional spiral and variable-density spiral data acquisitions for unambiguous
      water-fat decomposition with off-resonance blurring correction. In the spiral
      three-point Dixon technique, water-fat signal decomposition and image deblurring
      are performed based on the frequency maps that are directly derived from the
      acquired images. In the spiral two-point Dixon technique, several predetermined
      frequencies are tested to create a frequency map. The newly proposed techniques
      can achieve more effective and more uniform fat signal suppression when compared
      to the conventional spiral acquisition method with SPSP pulses.

PMID- 14587000
TI  - Modulation of the pharmacokinetics of macromolecular contrast material by avidin
      chase: MRI, optical, and inductively coupled plasma mass spectrometry tracking of
      triply labeled albumin.
AB  - The goal of this work was to develop an MRI method for mapping the clearance of
      interstitial macromolecular plasma proteins after their extravasation from
      permeable blood vessels. To that end, a well-defined window of exposure to
      elevated blood levels was generated by inducing rapid clearance of macromolecular
      contrast material from the blood. Experimental removal of the intravascular
      component allowed subsequent tracking of clearance from the interstitial
      compartment in the absence of further contrast extravasation. The contrast
      material was based on albumin triply labeled with biotin, fluorescent tag, and
      GdDTPA, allowing optical, inductively coupled plasma mass spectrometry (ICP-MS)
      and MRI detection. The biotin tag was used here for in vivo chasing of the
      contrast material from the blood by intravenous administration of avidin. Upon
      administration of avidin the contrast material disappeared from the blood vessels
      and was cleared by the liver and spleen as detected by MRI, fluorescence of blood
      samples and histological sections, and by ICP-MS. Nonbiotinylated fluorescent
      albumin was not affected by administration of avidin. Contrast material that
      extravasated from leaky blood vessels in a VEGF overexpressing tumor, prior to
      administration of avidin, was not cleared by the addition of avidin and showed
      continued interstitial convection. Thus, avidin-chase provides an effective tool
      for in vivo manipulation of the arterial input function by providing experimental
      control over the rate of clearance of the contrast material from the circulation.

PMID- 14587002
TI  - High-resolution diffusion and relaxation-edited magic angle spinning 1H NMR
      spectroscopy of intact liver tissue.
AB  - High-resolution magic angle spinning (HRMAS) (1)H NMR spectroscopy is ideal for
      monitoring the metabolic environment within tissues, particularly when spectra
      are weighted by physical properties such as T(1) and T(2) relaxation times and
      apparent diffusion coefficients (ADCs). In this study, spectral-editing using
      T(1) and T(2) relaxation times and ADCs at variable diffusion times was used in
      conjunction with HRMAS (1)H NMR spectroscopy at 14.1 T in liver tissue. To
      enhance the sensitivity of ADC measurements to low molecular weight metabolites a
      T(2) spin echo was included in a standard stimulated gradient spin-echo sequence.
      Fatty liver induced in rats by chronic orotic acid feeding was investigated using
      this modified sequence. An increase in the combined ADC for the co-resonant peaks
      glucose, betaine, and TMAO during fatty liver disease was detected (ADCs = 0.60
      +/- 0.11 and 0.35 +/- 0.1 * 10(-9) m(2)s(-1) (n = 3) for rats fed with and
      without orotic acid), indicative of a reduction in glucose and betaine and an
      increase in TMAO.

PMID- 14587003
TI  - Optimized gradient pulse for use with EPI employing active acoustic control.
AB  - The concept of active acoustic control was recently introduced by Mansfield and
      Haywood (MAGMA 2000:10:147-151) to ameliorate the problem of acoustic noise from
      MRI, particularly that from high-speed EPI. A 30 dB reduction in noise was
      previously achieved with the use of acoustic control operating at spot
      frequencies within a narrow band. In this work, a new acoustic gradient pulse is
      introduced that comprises an oscillating gradient of finite duration,
      incorporating a combination of frequencies within this band designed for use as
      the switched read gradient in echo-planar imaging (EPI). Employing this pulse
      with active acoustic control results in a reduction of acoustic noise by 50 dB.

PMID- 14587005
TI  - Proton HR-MAS spectroscopy and quantitative pathologic analysis of MRI/3D-MRSI
      targeted postsurgical prostate tissues.
AB  - Proton high-resolution magic angle spinning ((1)H HR-MAS) NMR spectroscopy and
      quantitative histopathology were performed on the same 54 MRI/3D-MRSI-targeted
      postsurgical prostate tissue samples. Presurgical MRI/3D-MRSI targeted healthy
      and malignant prostate tissues with an accuracy of 81%. Even in the presence of
      substantial tissue heterogeneity, distinct (1)H HR-MAS spectral patterns were
      observed for different benign tissue types and prostate cancer. Specifically,
      healthy glandular tissue was discriminated from prostate cancer based on
      significantly higher levels of citrate (P = 0.04) and polyamines (P = 0.01), and
      lower (P = 0.02) levels of the choline-containing compounds choline,
      phosphocholine (PC), and glycerophosphocholine (GPC). Predominantly stromal
      tissue lacked both citrate and polyamines, but demonstrated significantly (P =
      0.01) lower levels of choline compounds than cancer. In addition, taurine, myo
      inositol, and scyllo-inositol were all higher in prostate cancer vs. healthy
      glandular and stromal tissues. Among cancer samples, larger increases in choline,
      and decreases in citrate and polyamines (P = 0.05) were observed with more
      aggressive cancers, and a MIB-1 labeling index correlated (r = 0.62, P = 0.01)
      with elevated choline. The elucidation of spectral patterns associated with
      mixtures of different prostate tissue types and cancer grades, and the inclusion
      of new metabolic markers for prostate cancer may significantly improve the
      clinical interpretation of in vivo prostate MRSI data.

PMID- 14587004
TI  - MR spectroscopy of muscle and brain in guanidinoacetate methyltransferase (GAMT)
      deficient mice: validation of an animal model to study creatine deficiency.
AB  - As a model for guanidinoacetate methyltransferase (GAMT) deficiency in humans, a
      gene knockout mouse model was generated. Here we report on several metabolic
      abnormalities in these mice, observed by in vivo and in vitro MR spectroscopy. In
      (1)H MR spectra of brain and hindleg muscle a clearly reduced signal of creatine
      (Cr) was observed in GAMT-deficient (GAMT-/-) animals. Analysis of the (1)H MR
      spectra of GAMT-/- brain indicated little or no increase of a signal for
      guanidinoacetate (Gua). In proton MR spectra of muscle, a broad signal of low
      intensity was observed for Gua. However, substantial Gua accumulation in intact
      muscle tissue was unequivocally confirmed in high-resolution magic angle spinning
      spectra, in which the Gua signal was resolved as one clear sharp singlet. In
      (31)P MR analysis of brain and hindleg muscle a strongly reduced phosphocreatine
      (PCr) content was shown. In addition, a signal of phosphorylated Gua at 0.5 ppm
      upfield of PCr was observed, with much higher intensity in muscle than in brain.
      This signal decreased when ischemia was applied to the muscle and recovered after
      ischemia was released. Overall, the in vivo (31)P and (1)H MR spectroscopy of
      GAMT-/- mice is similar to that of human GAMT deficiency. This opens up new
      avenues for the fundamental study of tissue-type dependence of creatine synthesis
      and transport and for diagnostic and therapeutic aspects of creatine deficiencies
      in humans.

PMID- 14587006
TI  - Generalized diffusion tensor imaging and analytical relationships between
      diffusion tensor imaging and high angular resolution diffusion imaging.
AB  - A new method for mapping diffusivity profiles in tissue is presented. The Bloch
      Torrey equation is modified to include a diffusion term with an arbitrary rank
      Cartesian tensor. This equation is solved to give the expression for the
      generalized Stejskal-Tanner formula quantifying diffusive attenuation in
      complicated geometries. This makes it possible to calculate the components of
      higher-rank tensors without using the computationally-difficult spherical
      harmonic transform. General theoretical relations between the diffusion tensor
      (DT) components measured by traditional (rank-2) DT imaging (DTI) and 3D
      distribution of diffusivities, as measured by high angular resolution diffusion
      imaging (HARDI) methods, are derived. Also, the spherical tensor components from
      HARDI are related to the rank-2 DT. The relationships between higher- and lower
      rank Cartesian DTs are also presented. The inadequacy of the traditional rank-2
      tensor model is demonstrated with simulations, and the method is applied to
      excised rat brain data collected in a spin-echo HARDI experiment.

PMID- 14587007
TI  - Breast tissue differentiation using arterial spin tagging.
AB  - An arterial spin tagging (AST) pulse sequence has been developed to measure T(1)
      and relative blood perfusion. This full sequence is composed of three sequences:
      selective tagging, nonselective tagging, and nontagging. Perfusion quantification
      error resulting from imperfect inversion and acquisition slice profiles has been
      addressed in the literature. In this work, the error is reduced through the
      application of optimized Shinnar-Le Roux (SLR) RF pulses and a semi-log linear
      regression data-processing technique. A threshold approach based on the breast
      tissue T(1) and relative blood perfusion is introduced to show that these two
      parameters can be applied to breast tissue differentiation and potentially to
      cancer detection.

PMID- 14587008
TI  - In vivo monitoring of hepatic oxygenation changes in chronically ethanol-treated
      rats by functional magnetic resonance imaging.
AB  - In this study, functional magnetic resonance imaging (fMRI) was used to evaluate
      in vivo hepatic oxygenation changes in chronically ethanol (CE)-treated and pair
      fed (PF) control rats. Male Wistar rats were pair-fed an all-liquid diet
      containing 36% of total calories as either ethanol or dextrin-maltose for 8
      weeks. The rats were initially examined under normoxic conditions, and then
      subjected to 100% oxygen (hyperoxia), 10% oxygen (hypoxia), 5% carbon dioxide
      (hypercapnia), or an acute dose of ethanol (1.4 g/kg bw intraperitoneally). A
      T(2)-weighted spin-echo sequence, which may be more selective for sinusoidal
      (capillary bed) changes, was performed before, during, and after the four
      challenges. During hyperoxia, both the CE and PF rats showed a statistically
      significant increase in signal intensity (22% +/- 5% and 48% +/- 6%,
      respectively, P < 0.05) relative to normoxia, while hypoxic challenge decreased
      the signal intensity (9% +/- 4%, p>0.05 and 15% +/- 3%, P < 0.05, respectively).
      The hypercapnic challenge, which causes vasodilation, resulted in a small
      increase in signal intensity in CE-fed rats (5% +/- 3%, P > 0.05) and a
      significant increase in the PF rats (15% +/- 4%, P < 0.05), again consistent with
      expected changes in deoxyhemoglobin. With all three physiological challenges, the
      degree of change was less in CE rats compared to PF controls. An acute dose of
      ethanol that causes vasodilation also increased signal intensity, with no
      significant difference between the two groups. The signal intensity changes seen
      with fMRI were highly correlated with pulse oximeter readings (r(2) = 0.95; P <
      0.05). In conclusion, fMRI was shown to be a good noninvasive indicator of tissue
      deoxyhemoglobin changes in the liver. In addition, fMRI was able to detect
      subtle, early effects of CE administration (manifested as an impaired ability of
      the liver to respond adequately to oxygenation challenges), consistent with
      microvascular dysfunction.

PMID- 14587009
TI  - Regional atrophy in the brain of lissencephalic mouse lemur primates: measurement
      by automatic histogram-based segmentation of MR images.
AB  - Age-related regional cerebral atrophy was evaluated in a small lissencephalic
      primate, model of cerebral aging. Twelve mouse lemurs (Microcebus murinus), ages
      1.9-10.9 years (maximum life span: 12 years), were studied. 3D inversion-recovery
      fast spin-echo MR images (isotropic resolution = 234 mum) were recorded at 4.7 T
      with a surface coil actively decoupled from the transmitting birdcage probe. The
      surface coil-related sensitivity gradient was corrected by normalization with
      images from an agar and NaCl phantom. An automatic statistical segmentation
      technique based on a classification-maximization algorithm was tested on digital
      phantoms that mimicked the brain and applied to the 3D brain images. Segmented 3D
      maps that displayed gray matter, white matter, and cerebro-spinal fluid (CSF)
      voxels were computed. The ventricles and peri-encephalic spaces were categorized
      into 14 regions, defined on brain atlases on the basis of cytoarchitectural and
      anatomical criteria. The volume of CSF voxels belonging to each of these regions
      was calculated as an index of regional atrophy. Dilation of the mammillary fossa
      was an early event in the aging process. CSF accumulation within the occipital,
      parieto-temporal, temporal, and frontal ventral peri-encephalic spaces was
      particularly marked in the oldest animals that also displayed ophthalmologic
      alterations.

PMID- 14587010
TI  - Value of a blood pool contrast agent in MR venography of the lower extremities
      and pelvis: preliminary results in 12 patients.
AB  - The purpose of this study was to determine the value of a blood-pool contrast
      media (NC100150, Nycomed Imaging (now Amersham Health) Oslo, Norway) for
      evaluation of venous thrombosis of the deep veins of the pelvis and lower
      extremities. Twelve patients were prospectively evaluated with conventional X-ray
      venography (XRV) and MR venography (MRV) after injection of NC100150 (2 ml/kg
      body weight). The source images and 3D maximum intensity projection (MIP) were
      viewed on an independent workstation. Diagnosis was made in consensus from two
      radiologists. Diagnostic image quality was achieved in 87 veins with XRV and MRV.
      As determined by XRV, thrombus was present in 30 out of 87 veins (34.5%). There
      was agreement concerning absence or presence of thrombi in 83 out of 87 veins
      (95.4%; kappa = 0.9 +/- 0.05). Compared to XRV, overall sensitivity and
      specificity of blood-pool MRV were 93.3% and 96.5%, respectively. Two venous
      thromboses of the popliteal and posterior tibial vein were diagnosed in MRV, but
      not in XRV. Conversely, two venous thromboses below the knee had been missed by
      MRV. NC100150 allows prolonged and improved visualization of the peripheral
      vasculature and may overcome some limitations of gadolinium contrast media. A
      more complete examination of the proximal venous tree may be possible than with
      conventional XRV. Arterial and venous enhancement and motion artifacts can limit
      image interpretation.

PMID- 14587011
TI  - Triggered, navigated, multi-baseline method for proton resonance frequency
      temperature mapping with respiratory motion.
AB  - A technique is presented for the acquisition of temperature maps in the presence
      of variable respiratory motion using the proton resonance frequency (PRF) shift.
      The technique uses respiratory triggering, diaphragm position determination with
      a navigator echo, and the collection of multiple baseline images to generate
      temperature maps. Laser ablations were performed in an ex vivo liver phantom
      undergoing variable simulated respiratory motion and in vivo in four porcine
      livers, demonstrating a reduction of artifacts in the computed temperature maps
      compared with conventional single baseline techniques, both uncorrected and
      corrected for motion.

PMID- 14587012
TI  - Development of a tissue-equivalent MRI phantom using carrageenan gel.
AB  - A new tissue-equivalent MRI phantom based on carrageenan gel was developed.
      Carrageenan gel is an ideal solidifying agent for making large, strong phantoms
      in a wide variety of shapes. GdCl(3) was added as a T(1) modifier and agarose as
      a T(2) modifier. The relaxation times of a very large number of samples were
      estimated using 1.5-T clinical MRI equipment. The developed phantom was found to
      have a T(1) value of 202-1904 ms and a T(2) value of 38-423 ms when the GdCl(3)
      concentration was varied from 0-140 mumol/kg and the agarose concentration was
      varied from 0-1.6% in a carrageenan concentration that was fixed at 3%. The range
      of measured relaxation times covered those of all types of human tissue.
      Empirical formulas linking the relaxation time with the concentration of the
      modifier were established to enable the accurate and easy calculation of the
      modifier concentration needed to achieve the required relaxation times. This
      enables the creation of a phantom having an arbitrary combination of T(1) and
      T(2) values and which is capable of retaining its shape.

PMID- 14587013
TI  - Ultimate intrinsic signal-to-noise ratio for parallel MRI: electromagnetic field
      considerations.
AB  - A method is described for establishing an upper bound on the spatial encoding
      capabilities of coil arrays in parallel MRI. Ultimate intrinsic signal-to-noise
      ratio (SNR), independent of any particular conductor arrangement, is calculated
      by expressing arbitrary coil sensitivities in terms of a complete set of basis
      functions that satisfy Maxwell's equations within the sample and performing
      parallel imaging reconstructions using these basis functions. The dependence of
      the ultimate intrinsic SNR on a variety of experimental conditions is explored
      and a physically intuitive explanation for the observed behavior is provided
      based on a comparison between the electromagnetic wavelength and the distance
      between aliasing points. Imaging at high field strength, with correspondingly
      short wavelength, is shown to offer advantages for parallel imaging beyond those
      already expected due to the larger available spin polarization. One-dimensional
      undersampling of k-space yields a steep drop in attainable SNR for more than a 5
      fold reduction of scan time, while 2D undersampling permits access to much higher
      degrees of acceleration. Increased tissue conductivity decreases baseline SNR,
      but improves parallel imaging performance. A procedure is also provided for
      generating the optimal coil sensitivity pattern for a given acceleration, which
      will serve as a useful guide for future coil designs.

PMID- 14587014
TI  - k-t BLAST and k-t SENSE: dynamic MRI with high frame rate exploiting
      spatiotemporal correlations.
AB  - Dynamic images of natural objects exhibit significant correlations in k-space and
      time. Thus, it is feasible to acquire only a reduced amount of data and recover
      the missing portion afterwards. This leads to an improved temporal resolution, or
      an improved spatial resolution for a given amount of acquisition. Based on this
      approach, two methods were developed to significantly improve the performance of
      dynamic imaging, named k-t BLAST (Broad-use Linear Acquisition Speed-up
      Technique) and k-t SENSE (SENSitivity Encoding) for use with a single or multiple
      receiver coils, respectively. Signal correlations were learned from a small set
      of training data and the missing data were recovered using all available
      information in a consistent and integral manner. The general theory of k-t BLAST
      and k-t SENSE is applicable to arbitrary k-space trajectories, time-varying coil
      sensitivities, and under- and overdetermined reconstruction problems. Examples
      from ungated cardiac imaging demonstrate a 4-fold acceleration (voxel size 2.42 x
      2.52 mm(2), 38.4 fps) with either one or six receiver coils. k-t BLAST and k-t
      SENSE are applicable to many areas, especially those exhibiting quasiperiodic
      motion, such as imaging of the heart, the lungs, the abdomen, and the brain under
      periodic stimulation.

PMID- 14587015
TI  - Parsing local signal evolution directly from a single-shot MRI signal: a new
      approach for fMRI.
AB  - In this work a new single-shot MRI method, single-shot parameter assessment by
      retrieval from signal encoding (SS-PARSE), is introduced. This method abandons a
      fundamental simplifying assumption that is used in conventional MRI methods.
      Established MRI methods implicitly assume that the local intrinsic signal does
      not change its amplitude or phase during signal acquisition, even though these
      changes may be substantial, especially during the relatively long signals used in
      single-shot image acquisitions. SS-PARSE, on the other hand, acknowledges local
      decay and phase evolution, and models each signal datum as a sample from (k,t)
      space rather than k-space. Because of this more accurate signal model, SS-PARSE
      promises improved performance in terms of accuracy and robustness, but requires
      more intensive reconstruction computations. The theoretical properties of the
      method are discussed, and simulation results are presented that demonstrate more
      robust and accurate measurements of relaxation rate changes associated with brain
      activation in functional MRI (fMRI), freedom from geometric errors due to off
      resonance frequencies, and better tolerance of the large susceptibility gradients
      that occur naturally in parts of the brain. In addition, this technique has the
      potential to assess nonexponential relaxation behavior during a single-shot
      signal.

PMID- 14587016
TI  - Helical MR: continuously moving table axial imaging with radial acquisitions.
AB  - A technique for extended field of view MRI is presented. Similar to helical
      computed tomography, the method utilizes a continuously moving patient table, a
      2D axial slice that remains fixed relative to the MRI magnet, and a radial k
      space trajectory. A fully refocused SSFP acquisition enables spatial resolution
      comparable to current clinical protocols in scan times that are sufficiently
      short to allow a reasonable breathhold duration. RF transmission and signal
      reception are performed using the RF body coil and the images are reconstructed
      in real time. Experimental results are presented that illustrate the technique's
      ability to resolve small structures in the table-motion direction. Simulation
      experiments to study the steady-state response of the fully refocused SSFP
      acquisition during continuous table motion are also presented. Finally, whole
      body images of healthy volunteers demonstrate the high image quality achieved
      using the helical MRI approach.

PMID- 14587017
TI  - Accuracy and reproducibility in phase contrast imaging using SENSE.
AB  - The purpose of this study was to evaluate the accuracy and reproducibility of
      phase contrast imaging using the sensitivity encoding (SENSE) method at different
      reduction factors. Analytical expressions were derived that state how
      reproducibility is influenced for velocity and flow measurements. Computer
      simulations, and in vitro and in vivo studies were performed in order to validate
      these expressions and to assess how accuracy is affected when different reduction
      factors are applied. It was shown that reproducibility depends on the reduction
      and geometry factors. Since the geometry factor varies spatially, so does the
      reproducibility for phase contrast imaging. In areas with high geometry factors,
      the standard deviation (SD) may become so large that aliasing occurs. The
      accuracy of phase contrast imaging is not influenced directly when SENSE is used,
      but may be indirectly influenced due to high SDs of the measured phase that may
      subsequently cause aliasing. The current results show that it is possible to
      achieve accurate flow measurements even at high reduction factors. By taking the
      geometry factor into account, it may be possible to find areas where phase
      contrast imaging is accurate even at high reduction factors.

PMID- 14587018
TI  - Optimization of diffusion measurements using Cramer-Rao lower bound theory and
      its application to articular cartilage.
AB  - A novel approach to optimized diffusion measurements by minimizing the Cramer-Rao
      lower bound (CRLB) with respect to the b-values used for diffusion measurement
      was investigated. The applicability of the CRLB to these measurements is shown by
      the close agreement between the CRLB prediction and the actual precision obtained
      from experimental results. Where studies using a propagation-of-errors approach
      have restricted the optimization of the diffusion measurement to two b-values and
      to specific diffusion coefficient values, the CRLB approach sets no bounds on the
      number of b-values and is applicable to any system. The optimal number of b
      values depends on the ratio of the maximum and minimum diffusion coefficients in
      the sample (the D(ratio)) and on the number of acquisitions. For a D(ratio) above
      6.8 the optimal number of b-values increases to three; at a D(ratio) of 21.8 it
      increases to four. The optimized sampling schemes for ADC measurements in a
      variety of representative tissues found in the human body are given. For
      cartilage the optimal five-point acquisition scheme requires one measurement at a
      b-value of 0 and four at 1036 sec mm(-2), whereas brain requires one at 0, three
      at 660, and one at 1987 sec mm(-2).

PMID- 14587019
TI  - Characterization and propagation of uncertainty in diffusion-weighted MR imaging.
AB  - A fully probabilistic framework is presented for estimating local probability
      density functions on parameters of interest in a model of diffusion. This
      technique is applied to the estimation of parameters in the diffusion tensor
      model, and also to a simple partial volume model of diffusion. In both cases the
      parameters of interest include parameters defining local fiber direction. A
      technique is then presented for using these density functions to estimate global
      connectivity (i.e., the probability of the existence of a connection through the
      data field, between any two distant points), allowing for the quantification of
      belief in tractography results. This technique is then applied to the estimation
      of the cortical connectivity of the human thalamus. The resulting connectivity
      distributions correspond well with predictions from invasive tracer methods in
      nonhuman primate.

PMID- 14587020
TI  - Utilization of an intra-oral diamagnetic passive shim in functional MRI of the
      inferior frontal cortex.
AB  - Due to the presence of gross magnetic susceptibility artifacts, functional MRI
      (fMRI) has proved problematic in studies of the human inferior frontal cortex
      (IFC). There is a strong desire, therefore, to employ techniques that mitigate
      susceptibility artifacts in the IFC while preserving the imaging parameters of an
      fMRI study. It has been shown that the use of a single, strongly diamagnetic,
      intra-oral passive shim significantly improves the homogeneity of the static
      magnetic field (B(0)) and, as a result, alleviates the susceptibility artifacts
      within the IFC. In this study, practical issues regarding the use of an intra
      oral passive shim are examined. We investigated B(0) instabilities within the IFC
      resulting from subject head motion in order to calculate the effects of an intra
      oral passive shim on the temporal variance of an EPI time series. These studies
      show that the addition of an intra-oral passive shim improves both B(0)
      homogeneity and signal stability, and increases sensitivity to functional
      activation.

PMID- 14587021
TI  - Radial alternating TE sequence for faster fat suppression.
AB  - This study describes a steady-state sequence that uses a radial k-space
      trajectory and alternating echo times (TEs) between even and odd k-space views.
      The sequence generated a single data set that was used to reconstruct images with
      inherent fat suppression. This fat suppression results from the fat phase
      variation in alternate echoes giving rise to cancellation in the central portion
      of k-space. This new fat-suppression method provides inherent fat suppression in
      half the acquisition time relative to the radial two-point Dixon method. The
      improvement in k-space sampling efficiency is demonstrated in phantom and
      clinical images, and through measured point-spread functions (PSFs). As a result,
      the radial alternating TE sequence offers improved temporal resolution over a
      radial version of the two-point Dixon sequence by requiring fewer total
      projections to obtain the same effective resolution in water-based tissues.

PMID- 14587022
TI  - Variable-density spiral 3D tailored RF pulses.
AB  - A variable-density spiral method is presented for reducing three-dimensional
      tailored radiofrequency pulse duration. Pulse length reductions of 21-32% are
      possible, with only a small error in the desired excitation profile. The method
      is demonstrated using simulations, phantom experiments, and T(2)*-weighted images
      of brain regions with susceptibility-induced intravoxel dephasing. Four 19.7-ms
      shots were needed to excite a 5-mm-thick slice with reduced susceptibility
      artifacts in the sinus region at 3T.

PMID- 14587023
TI  - Degenerate mode birdcage volume coil for sensitivity-encoded imaging.
AB  - A volume birdcage coil for accelerated image encoding with parallel acquisition
      methods such as SENSE is demonstrated. The coil is degenerately tuned with both
      the standard homogeneous mode and the first gradient mode of the birdcage coil
      resonant at the Larmor frequency. Conventional and antisymmetric coupling
      structures allow imaging from each of these modes simultaneously. The coil for
      SENSE-type reconstruction with acceleration factors of up to 2-fold is
      demonstrated. The spatial distribution of the added noise from the SENSE
      reconstruction (g-factor map) due to geometrical arrangement of the two-channel
      system is estimated. The spatially averaged g-factors were found to be 1.21,
      1.36, and 1.55 for 1.3, 1.6, and 2-fold accelerations, respectively. The system
      was demonstrated in vivo using accelerated and nonaccelerated anatomical brain
      images at 1.5 T. The maximal 2-fold acceleration in this dual-mode degenerate
      birdcage coil offers the potential to extend SENSE-type image reconstruction
      methods to applications demanding uniform whole brain coverage.

PMID- 14587024
TI  - Scaffold attachment factors SAFB1 and SAFB2: Innocent bystanders or critical
      players in breast tumorigenesis?
AB  - Scaffold attachment factor B1 (SAFB1) and SAFB2 are large, multifunctional
      proteins that have been implicated in numerous cellular processes including
      chromatin organization, transcriptional regulation, RNA splicing, and stress
      response. While the two homologous proteins show high similarity, and functional
      domains are highly conserved, evidence suggests that they also have unique
      properties. For example, SAFB2 can be found in both the nucleus and cytoplasm,
      whereas SAFB1 seems to be mainly localized in the nucleus. In breast cancer
      cells, SAFBs function as estrogen receptor corepressors and growth inhibitors.
      SAFB protein expression is lost in approximately 20% of breast cancers.
      Interestingly, the two genes reside in close proximity, oriented head-to-head, on
      chromosome 19p13, a locus which is frequently lost in clinical breast cancer
      specimens. Furthermore, SAFB1 mutations have been identified in breast tumors
      that were not present in adjacent normal tissue. The possibility that SAFB1 and
      SAFB2 are novel breast tumor suppressor genes, and how they might function in
      this role, are discussed.

PMID- 14587025
TI  - Integrative nuclear FGFR1 signaling (INFS) as a part of a universal "feed-forward
      and-gate" signaling module that controls cell growth and differentiation.
AB  - A novel signaling mechanism is described through which extracellular signals and
      intracellular signaling pathways regulate proliferation, growth, differentiation,
      and other functions of cells in the nervous system. Upon cell stimulation,
      fibroblast growth factor receptor-1 (FGFR1), a typically plasma membrane
      associated protein, is released from ER membranes into the cytosol and
      translocates to the cell nucleus by an importin-beta-mediated transport pathway
      along with its ligand, FGF-2. The nuclear accumulation of FGFR1 is activated by
      changes in cell contacts and by stimulation of cells with growth factors,
      neurotransmitters and hormones as well as by a variety of different second
      messengers and thus was named integrative nuclear FGFR1 signaling (INFS). In the
      nucleus, FGFR1 localizes specifically within nuclear matrix-attached speckle
      domains, which are known to be sites for RNA Pol II-mediated transcription and co
      transcriptional pre-mRNA processing. In these domains, nuclear FGFR1 colocalizes
      with RNA transcription sites, splicing factors, modified histones, phosphorylated
      RNA Pol II, and signaling kinases. Within the nucleus, FGFR1 serves as a general
      transcriptional regulator, as indicated by its association with the majority of
      active nuclear centers of RNA synthesis and processing, by the ability of nuclear
      FGFR1 to activate structurally distinct genes located on different chromosomes
      and by its stimulation of multi-gene programs for cell growth and
      differentiation. We propose that FGFR1 is part of a universal "feed-forward-and
      gate" signaling module in which classical signaling cascades initiated by
      specific membrane receptors transmit signals to sequence specific transcription
      factors (ssTFs), while INFS elicited by the same stimuli feeds the signal forward
      to the common coactivator, CREB-binding protein (CBP). Activation of CBP by INFS,
      along with the activation of ssTFs by classical signaling cascades brings about
      coordinated responses from structurally different genes located at different
      genomic loci.

PMID- 14587027
TI  - Alternative splicing of fibronectin mRNAs in chondrosarcoma cells: role of far
      upstream intron sequences.
AB  - The fibronectin (FN) gene encodes multiple mRNAs through the process of
      alternative splicing, and production of certain isoforms is characteristic of a
      given cell type. Chondrocytes produce FNs that completely lack alternative exon
      EIIIA, and loss of inclusion of the exon is tightly linked to chondrogenic
      condensation of mesenchymal cells. The inclusion of a second exon, EIIIB, is high
      in embryonic cartilage, but declines with age. Multiple exons are omitted to
      produce the (V + C)-form that is highly specific for cartilage and chondrocytes.
      A rat chondrosarcoma cell line, RCS, was identified that preserves key features
      of the cartilage-specific splicing phenotype. RCS cells, which exclude exon
      EIIIA, and HeLa cells, which include exon EIIIA similar to mesenchymal cells,
      were used to assess the contribution of intron sequences flanking exon EIIIA to
      splicing regulation. Deletion of most of the intron downstream of the exon had
      little effect on splicing in either cell type. However, deletions within upstream
      intron 32-A reduced inclusion of the alternative exon in both cell types. The
      sequences involved lie more than 200 nucleotides away from the exon, but could
      not be localized to a single region by deletion mapping. These intronic sequences
      contribute to the efficiency of exon EIIIA recognition, but not to cell-type
      specific regulation. The normally inhibitory factor polypyrimidine tract binding
      protein promotes exon EIIIA inclusion in a manner that is partially dependent on
      the regulatory sequences within intron 32-A.

PMID- 14587026
TI  - Differential regulation of protein expression, growth and apoptosis by natural
      and synthetic retinoids.
AB  - All-trans retinoic acid (ATRA) can down regulate the anti-apoptotic protein Bcl-2
      and the cell cycle proteins cyclin D1 and cdk2 in estrogen receptor-positive
      breast cancer cells. We show here that retinoids can also reduce expression of
      the inhibitor of apoptosis protein, survivin. Here we have compared the
      regulation of these proteins in MCF-7 and ZR-75 breast cancer cells by natural
      and synthetic retinoids selective for the RA receptors (RARs) alpha, beta, and
      gamma then correlated these with growth inhibition, induction of apoptosis and
      chemosensitization to Taxol. In both cell lines ATRA and 9-cis RA induced the
      most profound decreases in cyclin D1 and cdk2 expression and also mediated the
      largest growth inhibition. The RARalpha agonist, Ro 40-6055 also strongly
      downregulated these proteins although did not produce an equivalent decrease in S
      phase cells. Only ATRA induced RARbeta expression. ATRA, 9-cis RA and 4-HPR
      initiated the highest level of apoptosis as determined by mitochondrial Bax
      translocation, while only ATRA and 9-cis RA strongly reduced Bcl-2 and survivin
      protein expression. Enumeration of dead cells over 96 h correlated well with
      downregulation of both survivin and Bcl-2. Simultaneous retinoid-mediated
      reduction of both these proteins also predicted optimal Taxol sensitization. 4
      HPR was much weaker than the natural retinoids with respect to Taxol
      sensitization, consistent with the proposed requirement for reduced Bcl-2 in this
      synergy. Neither the extent of cell cycle protein regulation nor AP-1 inhibition
      fully predicted the antiproliferative effect of the synthetic retinoids
      suggesting that growth inhibition requires regulation of a spectrum of RAR
      regulated gene products in addition even to pivotal cell cycle proteins.

PMID- 14587028
TI  - Sphingosine 1-phosphate effect on endothelial cell PAF synthesis: role in
      cellular migration.
AB  - Sphingosine 1-phosphate (S1P) and vascular endothelial growth factor (VEGF) are
      two inflammatory mediators capable of promoting endothelial cell (EC) migration
      and angiogenesis. As VEGF inflammatory effect is mediated by the synthesis of
      endothelial platelet-activating factor (PAF) which is also contributing to VEGF
      chemotactic activity, we wanted to assess if S1P can trigger PAF synthesis in EC
      and if S1P-induced migration is PAF-dependent. Treatment of bovine aortic EC
      (BAEC) with S1P (10(-10)-10(-6) M) increased dose- and time-dependently the
      synthesis of PAF by up to 3.3-fold above the basal level, with a maximal amount
      of PAF detected at 20 min post-stimulation. This biological response was
      attenuated by inhibiting p38 mitogen-activated protein kinase (MAPK), cytosolic
      or secreted phospholipase A(2) (cPLA(2), sPLA(2)) activity, suggesting that p38
      MAPK activation by S1P promotes the conversion of membrane phospholipids into PAF
      through the combined activation of cPLA(2) and sPLA(2). Interestingly,
      pretreatment of BAEC with extracellular PAF receptor antagonists (BN52021, 10(-5)
      M and CV3988, 10(-6) M) reduced by up to 42% the cellular migration induced by
      S1P (10(-6) M). These data demonstrate the capacity of S1P to induce PAF
      synthesis, which contributes in part to S1P chemotactic activity.

PMID- 14587029
TI  - Phosphorylation of PPARgamma via active ERK1/2 leads to its physical association
      with p65 and inhibition of NF-kappabeta.
AB  - Peroxisome proliferator-activated receptors (PPAR) are novel nuclear receptors
      and PPARgamma ligands have been shown to produce pro-apoptotic effects in many
      cancer cell types, including colon cancer. PPARgamma ligands exert their effect
      through PPARgamma-dependent (genomic) and PPARgamma-independent (non-genomic)
      mechanisms. Recent evidence suggests that PPARgamma ligands exert their pro
      apoptotic effects in part by directly antagonizing the NF-kappabeta pathway as
      well as through activation of the MAP kinase pathway. In this report, we have
      demonstrated that ciglitazone, a member of the thiazoldinedione class of
      PPARgamma ligands induces HT-29 colon cancer cells to undergo apoptosis and prior
      to apoptosis, ciglitazone exposure results in a transient phosphorylation of
      PPARgamma. This phosphorylation of PPARgamma was mediated through the ciglitazone
      induced activation of Erk1/2. PPARgamma phosphorylation affected the genomic
      pathway by being inhibitory to PPARgamma-DNA binding and PPRE transcriptional
      activity, as well as the non-genomic pathway by increasing the physical
      interaction of PPARgamma with p65, leading to the inhibition of NF-kappabeta.
      Ciglitazone induced phosphorylation of PPARgamma through the MAP kinase pathway
      provides a potential regulatory mechanism for PPARgamma's physical interaction
      with p65, leading to inhibition of NF-kappabeta and subsequent apoptosis.

PMID- 14587030
TI  - Medulloblastoma cell invasion is inhibited by green tea (-)epigallocatechin-3
      gallate.
AB  - Epigallocatechin-3-gallate (EGCG), the major green tea polyphenol, can reach the
      brain following oral intake and could thus act as an anti-tumoral agent targeting
      several key steps of brain cancer cells invasive activity. Because integrin
      mediated extracellular matrix recognition is crucial during the cell adhesion
      processes involved in carcinogenesis, we have investigated the effects of EGCG on
      different cellular integrins of the pediatric brain tumor-derived medulloblastoma
      cell line DAOY. Using flow cytometry, we report the levels of expression of
      several cell surface integrins in DAOY. These include high expression of alpha2,
      alpha3, and beta1 integrins, as well as alphav and beta3 integrins. Moreover, we
      provide evidence that EGCG can antagonize DAOY cell migration specifically on
      collagen by increasing cell adhesive ability through specific gene and protein
      upregulation of the beta1 integrin subunit. Our results suggest that this
      naturally occurring green tea polyphenol may thus be used as a nutraceutical
      therapeutic agent in targeting the invasive character of medulloblastomas.

PMID- 14587031
TI  - Matrix GLA protein and BMP-2 regulate osteoinduction in calcifying vascular
      cells.
AB  - Expression of matrix GLA protein (MGP), an alleged calcification inhibitor, is
      increased in calcified arteries. We used calcifying vascular cells (CVC) that
      form calcified nodules in vitro to clarify the importance of MGP in vascular cell
      calcification and differentiation. Unexpectedly, MGP dose-dependently increased
      calcification in CVC. It also increased expression of the osteogenic marker
      Cbfal, while decreasing expression of the smooth muscle marker alpha-actin as
      assessed by immunoblotting. Bone morphogenetic protein-2 (BMP-2), a known
      osteoinductive factor also increased calcification and osteogenic differentiation
      in CVC. We hypothesized that the effect of MGP was linked to that of BMP-2 since
      previous studies show that MGP modulates BMP-2 activity. Therefore, we compared
      the effect of MGP at different levels of exogenous BMP-2. Results showed that
      high BMP-2 levels significantly increased the stimulatory effect of low levels of
      MGP. A relative inhibition of calcification was observed at intermediate levels
      of MGP and a trend towards renewed stimulation at high levels of MGP. Thus,
      addition of MGP either promoted or inhibited calcification, depending on the
      relative amounts of BMP-2 and MGP. This was confirmed in human CVC with different
      relative expression of BMP-2 and MGP. Calcification in CVC with high relative
      expression of BMP-2 was inhibited by MGP, while calcification in CVC with low
      relative expression of BMP-2 was stimulated by MGP. MGP and BMP-2 both
      accelerated nodule formation, but had opposite effects on nodule size; MGP
      decreased while BMP-2 increased nodule size. The effect of BMP-2 may partly be
      explained by a BMP-2 induced decrease in MGP expression. Together, our results
      suggest that the effect of MGP on calcification and osteogenic differentiation is
      determined by availability of BMP-2.

PMID- 14587032
TI  - Secreted apolipoprotein E reduces macrophage-mediated LDL oxidation in an isoform
      dependent way.
AB  - As an inflammatory cell, the macrophage produces various oxidizing agents, such
      as free radical species. These can modify LDL as a secondary effect and doing so
      may favor atherogenic processes. Any molecule able to counteract these reactions
      would be of much benefit, especially if secreted by the macrophage itself at the
      lesion site. Such is the case for apolipoprotein E (apoE), which has been shown
      to exert antioxidant properties in some studies, mostly in relation to
      Alzheimer's disease. In this study, we assessed the antioxidant potential of the
      various isoforms of apoE (E2, E3, and E4) using a metal-induced LDL oxidation
      system with exogenous recombinant apoE and an in vitro model of macrophage
      mediated LDL oxidation. We found that all three isoforms had an antioxidant
      capacity. However, whereas apoE2 was the most protective isoform in the cell-free
      system, the opposite was observed in apoE-transfected J774 macrophages. In the
      latter model, cellular cholesterol efflux was found to be more important with
      apoE2, possibly explaining the larger quantity of oxidative indices observed in
      the medium. It is proposed that the antioxidant property of apoE results from a
      balance between direct apoE antioxidant capacities, such as the ability to trap
      free radicals, and potentially pro-oxidative indirect events associated with
      cholesterol efflux from cells. Our observations add to the therapeutic potential
      of apoE. However, they also suggest the need for more experiments in order to
      achieve careful selection of the apoE isoform to be targeted, especially in the
      perspective of apoE transgene use.

PMID- 14587034
TI  - Hepatic stellate cells uptake of retinol associated with retinol-binding protein
      or with bovine serum albumin.
AB  - Retinol is stored in liver, and the dynamic balance between its accumulation and
      mobilization is regulated by hepatic stellate cells (HSC). Representing less than
      1% total liver protein, HSC can reach a very high intracellular retinoid (vitamin
      A and its metabolites) concentration, which elicits their conversion from the
      myofibroblast to the fat-storing lipocyte phenotype. Circulating retinol is
      associated with plasma retinol-binding protein (RBP) or bovine serum albumin
      (BSA). Here we have used the in vitro model of GRX cells to compare incorporation
      and metabolism of BSA versus RBP associated [(3)H]retinol in HSC. We have found
      that lipocytes, but not myofibroblasts, expressed a high-affinity membrane
      receptor for RBP-retinol complex (KD = 4.93 nM), and both cell types expressed a
      low-affinity one (KD = 234 nM). The RBP-retinol complex, but not the BSA
      delivered retinol, could be dislodged from membranes by treatments that
      specifically disturb protein-protein interactions (high RBP concentrations).
      Under both conditions, treatments that disturb the membrane lipid layer
      (detergent, cyclodextrin) released the membrane-bound retinol. RBP-delivered
      retinol was found in cytosol, microsomal fraction and, as retinyl esters, in
      lipid droplets, while albumin-delivered retinol was mainly associated with
      membranes. Disturbing the clathrin-mediated endocytosis did not interfere with
      retinol uptake. Retinol derived from the holo-RBP complex was differentially
      incorporated in lipocytes and preferentially reached esterification sites close
      to lipid droplets through a specific intracellular traffic route. This direct
      influx pathway facilitates the retinol uptake into HSC against the concentration
      gradients, and possibly protects cell membranes from undesirable and potentially
      noxious high retinol concentrations.

PMID- 14587033
TI  - Effects of osteogenic protein-1 (OP-1, BMP-7) on gene expression in cultured
      medial collateral ligament cells.
AB  - Osteogenic protein-1 (OP-1, also called BMP-7), a member of the BMP family and
      the TGF-beta superfamily, induces formation of new bone and cartilage, but also
      regulates a wide array of processes. In the present study, the expression of
      several characteristic biochemical markers of ligaments, such as Six1, Scleraxis,
      aggrecan, and type I collagen in primary cultures of adult rat medial collateral
      ligament (MCL) cells was determined. The effects of OP-1 on cell proliferation
      and on gene expression were subsequently examined. OP-1 stimulated cell
      proliferation, alkaline phosphatase (AP) activity, and the steady-state mRNA
      levels of the transcription factor Runx2/Cbfa1 in a dose- and time-dependent
      manner. The mRNA levels of type I collagen only increased slightly, but the
      activity of the cloned collagen promoter increased by 2-fold in transiently
      transfected MCL cells. OP-1 also stimulated aggrecan mRNA expression. The mRNA
      levels of Six1 and Scleraxis were not detectably altered by OP-1. In control
      cultures, the steady-state mRNA levels of ActR-I, BMPR-IA, BMPR-IB, and BMPR-II
      increased as a function of time in culture. The mRNA levels of BMP-1 and -4
      increased significantly after 12 days, but those of BMP-2 and -6 did not change.
      The GDF-1, -3, -5, -6, and -8 mRNA levels in the control cultures also increased
      as a function of time. OP-1 treatment stimulated mRNA expression of BMPR-IA and
      BMPR-II, but had little effect on ActR-I and BMPR-IB mRNA expression. OP-1
      lowered the BMP-1, -2, and -6 mRNA levels without changing the BMP-4 mRNA level.
      OP-1 treatment also reduced the mRNA levels of GDFs detected. In summary, the
      present study demonstrated that OP-1 stimulated cell proliferation and mRNA
      expression of several biochemical markers in this ligament cell culture model and
      established the spatial and temporal appearance of several members of the TGF
      beta superfamily.

PMID- 14587035
TI  - Melatonin reduces Fenton reaction-induced lipid peroxidation in porcine thyroid
      tissue.
AB  - Free radicals and reactive oxygen species (ROS) participate in physiological and
      pathological processes in the thyroid gland. Bivalent iron cation (ferrous,
      Fe(2+)), which initiates the Fenton reaction (Fe(2+) + H2O2 --> Fe(3+) + *OH +
      OH(-)) is frequently used to experimentally induce oxidative damage, including
      that caused by lipid peroxidation. Lipid peroxidation is involved in DNA damage,
      thus indirectly participating in the early steps of carcinogenesis. In turn,
      melatonin is a well-known antioxidant and free radical scavenger. The aim of the
      study was to estimate the effect of melatonin on basal and iron-induced lipid
      peroxidation in homogenates of the porcine thyroid gland. In order to determine
      the effect of melatonin on the auto-oxidation of lipids, thyroid homogenates were
      incubated in the presence of that indoleamine in concentrations of 0.0, 0.00001,
      0.0001, 0.001, 0.01, 0.1, 0.25, 0.5, 1.0, 2.5, or 5.0 mM. To study melatonin
      effects on iron-induced lipid peroxidation, the homogenates were incubated in the
      presence of FeSO(4) (40 microM) plus H2O2 (0.5 mM), and, additionally, in the
      presence of melatonin in the same concentrations as above. The degree of lipid
      peroxidation was expressed as the concentration of malondialdehyde + 4
      hydroxyalkenals (MDA + 4-HDA) per mg protein. Melatonin, in a concentration
      dependent manner, decreased lipid peroxidation induced by Fenton reaction,
      without affecting the basal MDA + 4-HDA levels. In conclusion, melatonin protects
      against iron + H2O2-induced peroxidation of lipids in the porcine thyroid. Thus,
      the indoleamine would be expected to prevent pathological processes related to
      oxidative damage in the thyroid, cancer initiation included.

PMID- 14587036
TI  - Annulus cells release ATP in response to vibratory loading in vitro.
AB  - Mechanical forces regulate the developmental path and phenotype of a variety of
      tissues and cultured cells. Vibratory loading as a mechanical stimulus occurs in
      connective tissues due to energy returned from ground reaction forces, as well as
      a mechanical input from use of motorized tools and vehicles. Structures in the
      spine may be particularly at risk when exposed to destructive vibratory stimuli.
      Cells from many tissues respond to mechanical stimuli, such as fluid flow, by
      increasing intracellular calcium concentration ([Ca(2+)](ic)) and releasing
      adenosine 5'-triphosphate (ATP), extracellularly, as a mediator to activate
      signaling pathways. Therefore, we examined whether ATP is released from rabbit
      (rAN) and human (hAN) intervertebral disc annulus cells in response to vibratory
      loading. ATP release from annulus cells by vibratory stimulation as well as in
      control cells was quantitated using a firefly luciferin-luciferase assay.
      Cultured hAN and rAN cells had a basal level of extracellular ATP ([ATP](ec)) in
      the range of 1-1.5 nM. Vibratory loading of hAN cells stimulated ATP release,
      reaching a net maximum [ATP] within 10 min of continuous vibration, and shortly
      thereafter, [ATP] declined and returned to below baseline level. [ATP] in the
      supernatant fluid of hAN cells was significantly reduced compared to the control
      level when the cells received vibration for longer than 15 min. In rAN cells,
      [ATP] was increased in response to vibratory loading, attaining a level
      significantly greater than that of the control after 30 min of continuous
      vibration. Results of the current study show that resting annulus cells secrete
      ATP and maintain a basal [ATP](ec). Annulus cells may use this nucleotide as a
      signaling messenger in an autocrine/paracrine fashion in response to vibratory
      loading. Rapid degradation of ATP to ADP may alternatively modulate cellular
      responses. It is hypothesized that exposure to repetitive, complex vibration
      regimens may activate signaling pathways that regulate matrix destruction in the
      disc. As in tendon cells, ATP may block subsequent responses to load and modulate
      the vibration response. Rabbit annulus cells were used as a readily obtainable
      source of cells in development of an animal model for testing effects of
      vibration on the disc. Human cells obtained from discarded surgical specimens
      were used to correlate responses of animal to human cells.

PMID- 14587038
TI  - Strong induction of p73 protein in vivo coincides with the onset of apoptosis in
      rat liver after treatment with the hepatocarcinogen N-nitrosomorpholine (NNM).
AB  - Treatment of rats with genotoxic hepatocarcinogens such as N-nitrosomorpholine
      (NNM) causes severe hepatotoxicity associated with apoptosis of hepatocytes
      beginning after 12 h. Previously, we reported that after a single administration
      of high NNM dose p53 protein level increased in liver but not in testis and that
      the first wave of apoptosis preceded the induction of p53 indicating that
      apoptosis in liver was driven by a p53-independent pathway. We now show a
      pronounced upregulation of p73 protein, a p53-related gene product. The increase
      of p73 alpha and beta occurred already 6 h after NNM administration and preceded
      the onset of apoptosis by 6 h. Very strong p73 signals appeared 20 and 40 h post
      treatment and persisted for a few days, whereas p53 was induced only transiently
      at 20 and 40 h post-treatment. Immunohistochemical analysis revealed that unlike
      p53, p73 was detected in the nuclei of hepatocytes undergoing apoptosis.
      Following the upregulation of p73 levels, the products of several genes
      regulating DNA repair, e.g., GADD-45 and p53R2 and mediating apoptosis such as
      apoptosis inducing factor (AIF) were rapidly induced, whereas transient elevation
      of MDM-2 protein was delayed and coincided temporary with activation of p53
      protein. Interestingly, NF-kappaB another transcription factor responding to
      cellular stress was activated at 20 h after NNM administration and reached a
      maximum after an additional 20 h. Our data indicate that activated p73 protein
      may positively affect the induction and execution of apoptosis in response to
      genotoxic action of NNM.

PMID- 14587037
TI  - Rho exchange factor ECT2 is induced by growth factors and regulates cytokinesis
      through the N-terminal cell cycle regulator-related domains.
AB  - The ECT2 protooncogene plays a critical role in cytokinesis, and its C-terminal
      half encodes a Dbl homology-pleckstrin homology module, which catalyzes guanine
      nucleotide exchange on the Rho family of small GTPases. The N-terminal half of
      ECT2 (ECT2-N) contains domains related to the cell cycle regulator/checkpoint
      control proteins including human XRCC1, budding yeast CLB6, and fission yeast
      Cut5. The Cut5-related domain consists of two BRCT repeats, which are widespread
      to repair/checkpoint control proteins. ECT2 is ubiquitously expressed in various
      tissues and cell lines, but elevated levels of ECT2 expression were found in
      various tumor cell lines and rapidly developing tissues in mouse embryos.
      Consistent with these findings, induction of ECT2 expression was observed upon
      stimulation by serum or various growth factors. In contrast to other oncogenes
      whose expression is induced early in G1, ECT2 expression was induced later,
      coinciding with the initiation of DNA synthesis. To test the role of the cell
      cycle regulator/checkpoint control protein-related domains of ECT2 in
      cytokinesis, we expressed various ECT2 derivatives in U2OS cells, and analyzed
      their DNA content by flow cytometry. Expression of the N-terminal half of ECT2,
      which lacks the catalytic domain, generated cells with more than 4N DNA content,
      suggesting that cytokinesis was inhibited in these cells. Interestingly, ECT2-N
      lacking the nuclear localization signals inhibited cytokinesis more strongly than
      the derivatives containing these signals. Mutational analyses revealed that the
      XRCC1, CLB6, and BRCT domains in ECT2-N are all essential for the cytokinesis
      inhibition by ECT2-N. These results suggest that the XRCC1, CLB6, and BRCT
      domains of ECT2 play a critical role in regulating cytokinesis.

PMID- 14587039
TI  - Nuclear matrix bound fibroblast growth factor receptor is associated with
      splicing factor rich and transcriptionally active nuclear speckles.
AB  - We have used confocal microscopy combined with computer image analysis to
      evaluate the functional significance of a constitutively expressed form of the
      receptor tyrosine kinase FGFR1 (fibroblast growth factor receptor 1) in the
      nucleus of rapidly proliferating serum stimulated TE 671 cells, a medullobastoma
      human cell line. Our results demonstrate a limited number of large sites and
      numerous smaller sites of FGFR1 in the nuclear interior. The larger sites showed
      virtually complete colocalization (>90%) with splicing factor rich nuclear
      speckles while the smaller sites showed very limited overlap (<20%). Similar
      results were found for several other proliferating cell lines grown in culture.
      An in situ transcription assay was used to determine colocalization with
      transcription sites by incorporating 5-bromouridine triphosphate (BrUTP) followed
      by dual staining for BrUTP and FGFR1. These results combined with those from
      using an antibody against the large subunit of RNA polymerase II suggest a
      significant degree of colocalization (26-38%) over both the large and small
      sites. No colocalization was detected with sites of DNA replication. The spatial
      arrangements of FGFR1 sites and colocalization with nuclear speckles were
      maintained following extraction for nuclear matrix. Moreover, immunoblots
      indicated a significant enrichment of FGFR1 in the nuclear matrix fraction. Our
      findings suggest an involvement of a nuclear matrix bound FGFR1 in
      transcriptional and RNA processing events in the cell nucleus. We further propose
      that nuclear speckles, aside from a role in transcriptional/RNA processing
      events, may serve as fundamental regulatory factories for the integration of
      diverse signaling and regulatory factors that impact transcription and cellular
      regulation.

PMID- 14587040
TI  - Proteolytic cleavage of granulocyte colony-stimulating factor and its receptor by
      neutrophil elastase induces growth inhibition and decreased cell surface
      expression of the granulocyte colony-stimulating factor receptor.
AB  - Neutrophil elastase (NE) is a serine protease stored in the primary granules of
      neutrophils that proteolytically cleaves multiple cytokines and cell surface
      proteins on release from activated neutrophils. Recent reports of mutations in
      the gene encoding this enzyme in some patients with neutropenic syndromes
      prompted us to investigate whether granulocyte colony-stimulating factor (G-CSF)
      and its receptor (G-CSFR) are also substrates for NE. To further address this, we
      examined the effect of NE on G-CSF and the G-CSFR both in solution and on intact
      cells. Incubation of recombinant G-CSF or a G-CSFR form corresponding to its
      extracellular domain with purified NE resulted in rapid proteolytic cleavage of
      both proteins. Addition of NE to tissue culture medium or pretreatment of G-CSF
      with NE before its addition to media suppressed the growth of G-CSF-responsive
      cells. NE also cleaved the G-CSFR on the surface of intact cells resulting in a
      time-dependent reduction in cell surface expression of the G-CSFR. Notably,
      decreased G-CSFR surface expression resulting from treatment of cells with NE was
      also associated with a reduction in cell viability and proliferation in response
      to G-CSF. These results are the first to demonstrate that G-CSF and G-CSFR are
      proteolytically cleaved by NE and that NE-induced degradation of these proteins
      correlates with a reduction in the biologic activity of the cytokine and a
      decrease in the signaling function of the receptor because of decreased G-CSFR
      surface expression. These findings provide additional insights into mechanisms by
      which G-CSF/G-CSFR interactions may be modulated.

PMID- 14587041
TI  - Beta-globin gene cluster haplotypes in sickle cell patients from southwest Iran.
AB  - Sickle cell anemia in Iran is accompanied by a high level of HbF and mild
      clinical presentation. Here we report haplotypes of the beta gene cluster found
      in 81 randomly selected sickle cell patients, including 47 sickle cell anemia
      (SS), 17 sickle cell trait (AS), and 17 sickle/thalassemia (S/thal) from
      southwest Iran. We found all five common typical haplotypes as well as five
      atypical haplotypes in our patients. Except for four patients with homozygous
      Benin haplotype, none of the other African typical haplotypes were found in a
      homozygous state. Arab-Indian was found to be the most prevalent haplotype in the
      study population. This haplotype accounted for 51.1% as the homozygous form in SS
      patients, where 69.1% of chromosomes in these patients had the Arab-Indian
      haplotype. Bantu A2 was the second most prevalent haplotype among all patients.
      The mean %HbF in SS patients was 27.83 and in the homozygous Arab-Indian
      haplotype it was still higher (30.40%), while in AS patients the %HbF was only
      1.20. The high %Ggamma chain (71.81) in the Arab-Indian homozygous haplotype was
      concomitant with the presence of an Xmn I site in both chromosomes. The presence
      of the Arab-Indian haplotype as the predominant haplotype might be suggestive of
      a gene flow to/from Saudi Arabia or India. More haplotype investigations of a
      normal population can clarify the high incidence of Bantu A2 haplotype in our
      population.

PMID- 14587042
TI  - Initial management of immune thrombocytopenic purpura in adults: a randomized
      controlled trial comparing intermittent anti-D with routine care.
AB  - We conducted a randomized clinical trial in adults with a new diagnosis of ITP
      and a platelet count <30000/muL to test the hypothesis that initial intermittent
      treatment with anti-D may avoid or defer the need for splenectomy when compared
      to current routine care (glucocorticoid treatment, followed by splenectomy).
      Splenectomy was to be performed in the anti-D group if patients failed to respond
      to three consecutive anti-D treatments given within 10 days. The incidences of
      splenectomy were 14 of 37 (38%) in the routine care group and 14 of 33 (42%) in
      the anti-D group (absolute risk reduction = 4.6% in favor of the routine care
      group, 95% CI, -18.4 to 27.6%). However, splenectomy was performed prematurely,
      not according to the protocol, in 11 of 14 patients in the anti-D group. The
      median time to splenectomy was 36 days (range, 9-78) in the routine care group
      and 112 days (range, 19-558) in the anti-D group (P = 0.045 at 100 days after
      randomization, P = 0.840 at 1 year after randomization, using log-rank analysis).
      Patients in the anti-D group were treated with prednisone for fewer days (70
      days) compared to the routine care group (112 days, P = 0.01). No major bleeding
      events occurred. In this study, initial treatment of patients with intermittent
      anti-D initially deferred splenectomy. Whether our aggressive regimen of anti-D
      could have prevented splenectomy if it had been adhered to in all patients
      remains uncertain. However, compliance with this anti-D regimen was not feasible
      for many patients and/or their physicians.

PMID- 14587043
TI  - Overweight individuals are at increased risk for thrombotic thrombocytopenic
      purpura.
AB  - Our understanding of the pathophysiology of thrombotic thrombocytopenic purpura,
      TTP, has increased dramatically in the past few years with the identification of
      the role of ADAMTS13. Nonetheless, risk factors for the development of acute TTP
      are few. Informally, obesity was felt to be common in patients with TTP and so a
      formal study was undertaken to further define this association. We report our
      data in 105 patients with classical TTP as defined by thrombocytopenia and
      microangiopathic hemolytic anemia. We found that marked obesity is a previously
      unrecognized risk factor with an associated odds ratio of 7.6. Interestingly,
      despite this increased risk, obesity might well be associated with lower
      mortality, although this did not reach statistical significance.

PMID- 14587044
TI  - Dermatomyositis and myelodysplastic syndrome with myelofibrosis responding to
      methotrexate therapy.
AB  - Dermatomyositis (DM) has not yet been reported as a complication of
      myelodysplastic syndrome (MDS). A 50-year-old man was diagnosed as having MDS
      because of the presence of anemia, the appearance of immature cells in peripheral
      blood, and the abnormal cellular morphology. A few months later, high fever,
      myalgia and erythema developed. Although DM symptoms were resistant to high-dose
      corticosteroid administration, methotrexate (MTX) therapy improved not only the
      symptoms of DM but also hematologic findings related to MDS. This indicates that
      immunosuppressive therapy including MTX administration can be useful for patients
      with MDS with autoimmune symptoms.

PMID- 14587045
TI  - Beta-thalassemia in association with a new delta-chain hemoglobin variant
      [delta116(g18)Arg-->Leu]: implications for carrier screening and prenatal
      diagnosis.
AB  - We describe a complicated genetic counseling and prenatal diagnostic case
      involving an East Indian couple that had lost two consecutive pregnancies.
      Hemoglobinopathy screening was conducted to investigate the possibility of Hb
      Bart's hydrops fetalis or Hb H hydrops fetalis. The initial work-up indicated
      that alpha-thalassemia was not a contributing factor, with both parents being
      carriers of single gene deletions (-alpha(3.7)/alphaalpha). However, the Hb
      electrophoresis results indicated that the couple might be at risk for having
      children with Hb E/Hb Lepore disease. Subsequent DNA testing demonstrated that
      the father carried the Hb E mutation, but failed to confirm that the mother
      carries the Hb Lepore deletion. Sequence analysis revealed that the mother was
      heterozygous for a common East Indian beta(0)-thalassemia mutation, yet had a
      normal level of Hb A(2). The mother also carried a previously unreported missense
      mutation of the delta-globin gene, in cis with the beta(0)-thalassemia mutation,
      which gave rise to the minor Hb variant originally misidentified as Hb Lepore.
      This case illustrates the importance of comprehensive molecular analyses for
      accurate assessment of genetic risks for hemoglobinopathy syndromes.

PMID- 14587046
TI  - Rhinolalia as a presenting sign of pneumomediastinum complicating post peripheral
      blood stem cell transplantation bronchiolitis obliterans.
AB  - A 26-year-old male with graft vs. host disease (GVHD) presented with rhinolalia
      (a squeaky voice of nasal quality) as a presenting sign for pneumonasopharynx and
      pneumomediastinum secondary to bronchiolitis obliterans. The patient underwent
      HLA-identical related peripheral blood stem cells transplantation 8 months before
      the diagnosis. Three weeks after transplantation he began to suffer from GVHD
      Grade III that involved the gut, liver, and skin and later on the lungs. Due to
      severe obstructive bronchiolitis obliterans the patient developed intensive cough
      evolving into pneumomediastinum and pneumonasopharynx with rhinolalia. The
      patient was treated conservatively with complete resolution. Although rare,
      pneumomediastinum and pneumonasopharynx can be a life-threatening event, and one
      should be aware of the signs and symptoms on physical examination, which may be
      as subtle as rhinolalia alone.

PMID- 14587047
TI  - High-dose intravenous immunoglobulin treatment in two patients with acquired
      factor V inhibitors.
AB  - We report two patients who developed acquired factor V (FV) inhibitors not
      related to exposure to bovine thrombin. Associated conditions were found in one
      patient (surgery, antibiotic administration) but none in the other one. Bleeding
      complications occurred only in the patient with idiopathic FV inhibitor, leading
      to packed red cell infusion. Laboratory findings showed the presence of specific
      FV inhibitors with titers of 5.5 and 5 Bethesda units, respectively. These two
      patients received high-dose intravenous immunoglobulin and FV levels normalized
      within a few days with a concomitant disappearance of FV inhibitors.

PMID- 14587048
TI  - Rapid detection of six common Mediterranean and three non-Mediterranean alpha
      thalassemia point mutations by reverse dot blot analysis.
AB  - We describe the implementation of reverse dot blot (RDB) hybridization as a rapid
      nonradioactive method for the identification of six frequent globin gene point
      mutations in the Mediterranean population: alpha(Hph)alpha: alpha2 IVS I donor
      site GGTGAGG --> GG-----; alpha(NcoI)alpha: alpha2 initiation codon ATG --> ACG;
      alpha(TSaudi)alpha: alpha2Poly A signal AATAA --> AATAAG; alpha(Icaria)alpha:
      alpha2 termination codon TAA --> AAA (Ter --> LYS); alpha(CS)alpha: alpha2
      termination codon TAA --> CAA (Ter --> gly); alphaalpha(NcoI): alpha1 initiation
      codon ATG --> GTG; and three alpha2 globin gene point mutations found in
      immigrants in Italy: alpha(T-Quongsze)alpha: alpha2 codon 12 CTG --> CCG (Leu -->
      Pro); alpha(Seal Rock)alpha: alpha2 termination codon TAA --> GAA (TER --> GLU);
      and alpha(Koyadora)alpha: alpha2 termination codon TAA --> TCA (TER --> SER). The
      method uses the principle of allele-specific oligonucleotide (ASO) hybridization,
      but it is a nonradioactive method and permits rapid and simultaneous typing of
      point mutations and small deletions.

PMID- 14587049
TI  - Erythrophagocytosis in paroxysmal cold hemoglobinuria.

PMID- 14587050
TI  - Visceral leishmaniasis masquerading as myelodysplasia.
AB  - We report a case of a 61-year-old man with head and neck cancer who presented
      with pancytopenia two months after the completion of his chemotherapy and was
      diagnosed with myelodysplasia on the basis of two bone marrow examinations,
      before the correct diagnosis of visceral leishmaniasis was established with
      splenectomy.

PMID- 14587051
TI  - Facial palsy as first presentation of acute myeloid leukemia.
AB  - Granulocytic sarcoma or chloroma is a tumor composed of myeloblast or monoblast.
      These tumors may be found in any location of the body and occur in 5% of acute
      myeloid leukemia (AML) cases and are more common in pediatric patients. In this
      report we describe the case of a 27-year-old male who developed lower motor
      neuron seventh nerve palsy followed by swelling of the parotid gland. Fine-needle
      aspiration cytology (FNAC) of the soft tissue swelling revealed scattered blasts,
      and peripheral smear and bone marrow aspirate examination suggested AML. This is
      a rare presentation of a granulocytic sarcoma leading to a diagnosis of AML.

PMID- 14587052
TI  - Urinary excretion of retinol in patients with multiple myeloma: a preliminary
      study.
AB  - Urinary excretion of vitamin A was studied in patients with multiple myeloma
      (MM). Eight of the 12 patients studied excreted retinol in urine; only one of
      them had elevated serum creatinine (115-150 micromol/L). There was a highly
      significant correlation between urinary retinol and serum creatinine (P <
      0.0004). Urinary retinol correlated also with urine protein (P < 0.0001) and
      albumin (P = 0.001), but not with urinary immunoglobulin light chains. Urinary
      retinol excretion may be an early manifestation of renal dysfunction in MM
      patients. The effect of urinary retinol excretion on vitamin A homeostasis in MM
      deserves further study.

PMID- 14587053
TI  - Thalidomide and dexamethasone therapy of myeloma in a patient with previously
      untreated B-chronic lymphocytic leukemia.
AB  - A 67-year-old woman with previously untreated lambda-positive B-chronic
      lymphocytic leukemia (CLL) had kappa-positive myeloma develop that was treated
      with daily thalidomide and intermittent dexamethasone. After 4 months, there was
      a marked reduction in marrow plasmacytosis, urine kappa chains, and peripheral
      blood and marrow lymphocytosis. She reduced her thalidomide (but not
      dexamethasone) doses after 6 months, because she had symptoms of peripheral
      neuropathy. Although blood lymphocyte concentrations remained normal, she had
      progression of myeloma and died. Thalidomide and dexamethasone therapy similar to
      that administered for myeloma alone may be effective treatment for myeloma in
      patients with preexisting B-CLL and may also have anti-B-CLL activity.

PMID- 14587054
TI  - Pro CR global: an effective screening test for thrombophilia.
AB  - In the present study, the Pro C(R) Global test was evaluated as a screening test
      for estimation of the activity of the main plasma components of the anticoagulant
      protein C (PC) / protein S (PS) pathway; 300 patients with a history of
      thrombosis were investigated for Pro C(R) Global. It was positive in 74 patients.
      Tests for estimation of PC, PS, activated protein C resistance (APCR), and lupus
      anticoagulant (LAC) were performed in all the patients with abnormal Pro C(R)
      Global and in 10 patients with normal Pro C(R) Global. In all, 66 of the 74
      patients had a defect in PC/PS/APCR or LAC; 18 patients had both PC and PS
      deficiency, 25 had PS deficiency alone, 10 had PC deficiency alone, one had APCR
      alone, eight had PS, PC deficiency with APCR, and four had PS deficiency with
      APCR. In the 10 patients who tested negative with the Pro C(R) Global test, PC,
      APCR, and LAC were negative in all. However, PS deficiency was seen in two of
      them. The sensitivity and specificity of Pro C(R) Global, calculated with respect
      to positivity of PC, PS, LAC, or APCR as the gold standard, were 97% and 50%,
      respectively. The diagnostic accuracy of the assay was 88.1%. It is thus
      recommended that Pro C(R) Global can be used effectively as a screening test to
      detect abnormality in the PC/PS/APCR/LAC pathway.

PMID- 14587055
TI  - Long-lasting fever of unknown origin preceding the diagnosis of intravascular
      lymphomatosis: a further case stimulates some remarks.
AB  - Neurological and skin involvements usually dominate the clinical presentation of
      intravascular lymphomatosis (IL), while fever is the most frequent general sign.
      However, an onset only characterized by fever of unknown origin (FUO) has been
      rarely reported. We would like to describe a further case of IL, which presented
      a long-lasting FUO before the diagnosis. At admission, physical examination
      detected hepatosplenomegaly without lymph nodes enlargement or dermatological or
      neurological abnormalities. Significant laboratory data included severe anemia,
      leukopenia, thrombocytopenia, and increased serum LDH. Moreover, a chest CT
      evidenced bilateral multiple pulmonary infiltrates and pleural effusion. After
      the development of proteinuria, a diagnosis of large B-cell intravascular
      lymphoma was made with a renal biopsy 10 months after the onset of the clinical
      manifestations. So far, more than 100 cases of IL have been reported and the
      diagnosis often turned out to be difficult, as clinical signs did not point to a
      lymphoproliferative disorder. This report confirms that FUO is not only
      frequently associated with IL but that it even marks the real onset of the
      disease. We are then tempted to conclude that undiagnosed fever is not so rare in
      IL and if we call it FUO, it is only because diagnosis is necessarily elusive and
      hence time-consuming.

PMID- 14587056
TI  - Sickle cell patient with an acute chest syndrome and a negative chest X-ray:
      potential role of the ventilation and perfusion (V/Q) lung scan.
AB  - Acute chest syndrome (ACS) in sickle cell disease is caused by thromboemboli in
      the pulmonary vasculature. The diagnostic criteria include the presence of
      pulmonary infiltrate(s) on chest x-ray. This case report suggests that a V/Q scan
      may play a diagnostic role in sickle cell patients with symptoms of ACS and a
      negative chest x-ray.

PMID- 14587057
TI  - Significance of increasing adhesion of cord blood hematopoietic cells and a new
      method: platelet microparticles.
AB  - Hematopoietic recovery after transplantation with cord blood (CB) is slower than
      with bone marrow (BM) and mobilized peripheral blood. Adhesion molecules (AMs) on
      hematopoietic cells are involved in hematopoietic cells' homing. It may be
      possible to enhance CB CD34+ cells engraftment by increasing their expressions of
      AM. Twenty-three patients with childhood acute leukemia treated with unrelated
      CBT were studied. It was found that the time to neutrophil recovery correlated
      with CXCR4 and the time to platelet recovery correlated with both CD62L and
      CXCR4. Platelet microparticles (PMPs) carry some AMs such as aIIb b (CD41), P
      selectin (CD62P), and CXCR4, CD34+ cells express platelet-binding antigens (CD162
      and CD11b). It was found that AMs were increased dramatically on CD34+ cells
      surface in the presence of PMPs, and CD34+ cells covered with PMPs adhered better
      to human umbilical vein endothelial cells and fibronectin. These findings
      suggested that PMPs could increase adhesion of donor's cells to host BM in CBT.

PMID- 14587058
TI  - Acute lymphoblastic leukemia without the Philadelphia chromosome occurring in
      chronic myelogenous leukemia with the Philadelphia chromosome.
AB  - The blast crisis in chronic myelogenous leukemia (CML) is related to the
      evolution of a Philadelphia chromosome (Ph)-positive clone. Secondary chromosomal
      abnormalities accompanied by t(9;22) are found in 70-80% of blast crises. Here we
      describe a patient with Ph-positive CML, who developed Ph-negative acute
      lymphoblastic leukemia (ALL). A 52-year-old man was diagnosed with CML with the
      Ph chromosome in the chronic phase. He achieved a partial cytogenetic response
      after 4 months of imatinib mesylate therapy. After 8 months, common ALL occurred.
      At that time his karyotype was normal and the Ph chromosome was not noted.

PMID- 14587059
TI  - Disseminated Mycobacterium kansasii infection with pulmonary alveolar proteinosis
      in a patient with chronic myelogenous leukemia.
AB  - A 64-year-old woman with chronic myelogenous leukemia (CML) was admitted due to
      prolonged fever and lung infiltrates. An open lung biopsy was required to make
      the diagnosis of pulmonary alveolar proteinosis (PAP) and infection with
      Mycobacterium kansasii. She was treated successfully with combined
      antimycobacterial therapy for 14 months. However, the leukemia progressed and the
      patient developed recurrent bilateral lung infiltrates. Blood and bronchoalveolar
      fluid cultures yielded growth of Acinetobacter. She died shortly thereafter due
      to septic shock. The relationship between M. kansasii infection, PAP, and
      abnormal host defense in CML is discussed.

PMID- 14587060
TI  - Major depression and psoriasis activation due to interferon-alpha in a patient
      with chronic myeloid leukemia; "overlooked and/or misdiagnosed adverse reaction
      in malignant disease".

PMID- 14587061
TI  - Splenic hematoma in Hb S-beta+thalassemia.

PMID- 14587062
TI  - Fluorescence resonance energy transfer between donor-acceptor pair on two
      oligonucleotides hybridized adjacently to DNA template.
AB  - We use fluorescein as the energy donor and rhodamine as the acceptor to measure
      the efficiency of fluorescence resonance energy transfer (FRET) in a set of
      hybridized DNA constructs. The two fluorophores are covalently attached via
      linkers to two separate oligonucleotides with fluorescein at the 3' end of one
      oligonucleotide and rhodamine at the 5' end or in the middle of another
      nucleotide. For the FRET analysis both fluorophore-labeled oligonucleotides are
      hybridized to adjacent sections of the same DNA template to form a three
      component duplex with a one base gap between the two labeled oligonucleotides. A
      similar configuration is implemented for a quantitative real-time polymerase
      chain reaction (PCR) with LightCycler technology, where a 1-5 base separation
      between donor and acceptor is recommended to optimize energy transfer
      efficiencies. Our constructs cover donor-acceptor separations from 2 to 17 base
      pairs (approximately 10-70 A). The results show that, when the two fluorophores
      are located at close distances (less than 8 base separation), FRET efficiencies
      are above 80%, although there may be ground-state interactions between
      fluorophores when the separation is under about 6 bases. Modeling calculations
      are used to predict the structure of these three-component constructs. The duplex
      mostly retains a normal double helical structure, although slight bending may
      occur near the unpaired base in the DNA template. Stable and reproducible energy
      transfer is also observed over the distance range investigated here in real-time
      thermal cycling. The study identifies important parameters that determine FRET
      response in applications such as real-time PCR.

PMID- 14587063
TI  - Simple PbII fluorescent probe based on PbII-catalyzed hydrolysis of
      phosphodiester.
AB  - A new fluorescent probe for PbII, p-nitrophenyl 3H-phenoxazin-3-one-7-yl
      phosphoric acid (NPPA), was designed and synthesized by linking resorufin
      (serving as a fluorophore and electron acceptor) to p-nitrophenol (serving as a
      fluorescence quencher and electron donor) through phosphodiester bonds. When NPPA
      was irradiated with light, intramolecular fluorescence self-quenching took place
      because of the photoinduced electron transfer from the donor to the acceptor.
      However, upon the addition of PbII, the phosphate ester bonds in the probe were
      cleaved and the fluorophore was released, accompanying the retrievement of
      fluorescence.

PMID- 14587064
TI  - Conformation of alpha zeins in solid state by Fourier transform IR.
AB  - The major maize storage proteins (alpha zeins) are deposited as an insoluble mass
      in the protein bodies of the endosperm. Because they are insoluble in water, most
      structural studies are performed in alcohol solutions. To solve the question
      raised by several authors about denaturation of the alpha zein structure by
      alcohol, we analyze the secondary structure of alpha zeins prepared with and
      without solubilization in alcohol (corn gluten meal and protein bodies with high
      concentrations of alpha zeins and traces of beta zeins). The secondary structures
      of alpha zeins are analyzed in the solid state by Fourier transform IR
      spectroscopy (FTIR) in KBr pellets and solid-state 13C-NMR spectroscopy. The
      proportion of secondary structures obtained by FTIR of alpha zeins prepared with
      and without solubilization in alcohol yield almost identical proportions of alpha
      helices and beta sheets. The proportion of alpha helices (43%) agrees with that
      measured by circular dichroism in an alcohol solution. However, the proportion of
      beta sheets (28%) is higher than the one measured by the same technique. Gluten
      and protein body samples with high beta zein content showed higher beta sheet and
      lower alpha helix proportions than that obtained for alpha zein preparations. The
      solid-state 13C-NMR spectra show the carbonyl peak for the alpha zeins at delta
      176 and for the sample rich in beta zeins at delta 172, which demonstrates the
      presence of a high content of alpha helices and beta sheets, respectively. These
      results indicate that alcohol solubilization does not affect the conformation of
      alpha zeins, validating the secondary structure measurements in solution.

PMID- 14587065
TI  - Binding of quercetin with human serum albumin: a critical spectroscopic study.
AB  - Flavonols are plant pigments that are ubiquitous in nature. Quercetin
      (3,3',4',5,7-pentahydroxyflavone) and other related plant flavonols have come
      into recent prominence because of their usefulness as anticancer, antitumor, anti
      AIDS, and other important therapeutic activities of significant potency and low
      systemic toxicity. Quercetin is intrinsically weakly fluorescent in aqueous
      solution, showing an emission maximum at approximately 538 nm. Upon binding to
      human serum albumin (HSA), quercetin undergoes dramatic enhancement in its
      fluorescence emission intensity, along with the appearance of dual emission
      behavior, consisting of normal and excited-state proton transfer (ESPT)
      fluorescence. In addition, the occurrence of a third emitting species has been
      noted for the first time. This is attributed to a electronic ground-state complex
      formed in the protein environment. High values of the fluorescence anisotropy (r)
      are obtained in the presence of HSA for the ESPT tautomer (r = 0.18), as well as
      the complex species (r = 0.37) of quercetin, indicating that the precursor ground
      state molecules for both these emitting species of quercetin molecules are
      located in the motionally constrained sites of HSA. The steady-state emission
      data suggest that quercetin binds to two distinct sites in HSA from which the
      emissions from the normal tautomer and complex species take place. The
      preliminary results of studies on emission decay kinetics are also reported
      herein. Studies by far-UV circular dichroism spectroscopy reveal that binding of
      quercetin induces no significant perturbation in the secondary structure of HSA.

PMID- 14587066
TI  - 3'-azido-3'-deoxythymidine binding to ribonuclease A: model for drug-protein
      interaction.
AB  - Ribonuclease A (RNase A) with several high affinity binding sites is a possible
      target for many organic and inorganic molecules. 3'-Azido-3'-deoxythymidine (AZT)
      is the first clinically effective drug for the treatment of human
      immunodeficiency virus (HIV) infection. The drug interactions with protein and
      nucleic acids are associated with its mechanism of action in vivo. This study was
      designed to examine the interaction of AZT with RNase A under physiological
      conditions. Reaction mixtures of constant protein concentration (2%) and
      different drug contents (0.0001-0.1 mM) are studied by UV-visible, FTIR, and
      circular dichroism spectroscopic methods in order to determine the drug binding
      mode, the drug binding constant, and the effects of drug complexation on the
      protein and AZT conformations in aqueous solution. The spectroscopic results
      showed one major binding for the AZT-RNase complexes with an overall binding
      constant of 5.29 x 10(5) M(-1). An increase in the protein alpha helicity was
      observed upon AZT interaction, whereas drug sugar pucker remained in the C2'
      endo/anti conformation in the AZT-RNase complexes.

PMID- 14587067
TI  - Interaction of clinically important human DNA topoisomerase I poison, topotecan,
      with double-stranded DNA.
AB  - Topotecan (TPT), a water-soluble derivative of camptothecin, is a potent
      antitumor poison of human DNA topoisomerase I (top1) that stabilizes the cleavage
      complex between the enzyme and DNA. The role of the recently discovered TPT
      affinity to DNA remains to be defined. The aim of this work is to clarify the
      molecular mechanisms of the TPT-DNA interaction and to propose the models of TPT
      DNA complexes in solution in the absence of top1. It is shown that TPT molecules
      form dimers with a dimerization constant of (4.0 +/- 0.7) x 10(3) M(-1) and the
      presence of DNA provokes more than a 400-fold increase of the effective
      dimerization constant. Flow linear dichroism spectroscopy accompanied by circular
      dichroism, fluorescence, and surface-enhanced Raman scattering experiments
      provide evidence that TPT dimers are able to bind DNA by bridging different DNA
      molecules or distant DNA structural domains. This effect may provoke modification
      of the intrinsic geometry of the cruciform DNA structures, leading to the
      appearance of new crossover points that serve as the sites of the top1 loading
      position. The data presume the hypothesis of TPT-mediated modulation of top1-DNA
      recognition before ternary complex formation.

PMID- 14587068
TI  - Pinacyanol as effective probe of fibrillar beta-amyloid peptide: comparative
      study with Congo Red.
AB  - The binding of pinacyanol (PIN), a cationic cyanine dye, to beta-amyloid fibrils
      (Abeta), which are associated with Alzheimer disease, was quantified by
      absorption spectrophotometry to measure the concentration of PIN bound to Abeta
      as a function of the Abeta concentration or by means of the separation of free
      PIN from bound PIN by centrifugation and subsequent analysis of the supernatant
      by visible-absorption spectrophotometry. Both methods gave equivalent results.
      The stoichiometry of PIN binding to Abeta was 1, and the curve representing the
      concentration effect of Abeta on the concentration of a dye-Abeta complex showed
      a biphasic curve instead of the hyperbolic curve that is characteristic of weak
      ligand-macromolecule interactions [e.g., as shown by Congo Red (CR)]). This and
      the fact that a Scatchard plot could not be fitted to the experimental data
      suggested that PIN binds tightly to Abeta. A comparison to the interaction of CR
      with Abeta led us to conclude that PIN is more sensitive than CR.

PMID- 14587070
TI  - Interaction of anticancer drug cisplatin with guanine: density functional theory
      and surface-enhanced Raman spectroscopy study.
AB  - Surface-enhanced Raman spectroscopy (SERS) in a silver sol assisted by density
      functional theory (DFT) calculations is shown to be a promising tool in the
      characterization of platinum complexes and their interaction with nucleic acid
      bases. This is demonstrated using cisplatin and guanine as a model. The energies
      and geometric parameters of cisplatin, guanine, and their reaction products are
      calculated at Becke's nonlocal three parameter exchange and correlation
      functional and the Lee-Yang-Parr correlation functional level using the 6
      31++G(d,p) basis set on the light elements and the effective core potential by
      Hay and Wadt on platinum. Available X-ray crystallography data are mostly in
      agreement with predictions within the experimental precision level, although Pt-N
      bond lengths tend to be systematically overestimated. The normal Raman spectrum
      of cisplatin is assigned. The SERS spectra of cisplatin and its reaction product
      with guanine are measured from 10(-6) M aqueous solution. The observed spectral
      changes in the SERS spectrum of guanine upon cisplatin binding are modeled by DFT
      calculations. The best agreement between theory and experiment is achieved when
      the adsorbed reaction product is assumed to be the 1:1 adduct cis-Pt(NH3)2ClG in
      which Pt is bound to N7 and guanine is deprotonated at N9.

PMID- 14587069
TI  - Distinguishing and grading human gliomas by IR spectroscopy.
AB  - As a molecular probe of tissue composition, IR spectroscopy can potentially serve
      as an adjunct to histopathology in detecting and diagnosing disease. This study
      demonstrates that cancerous brain tissue (astrocytoma, glioblastoma) is
      distinguishable from control tissue on the basis of the IR spectra of thin tissue
      sections. It is further shown that the IR spectra of astrocytoma and glioblastoma
      affected tissue can be discriminated from one another, thus providing insight
      into the malignancy grade of the tissue. Both the spectra and the methods
      employed for their classification reveal characteristic differences in tissue
      composition. In particular, the nature and relative amounts of brain lipids,
      including both the gangliosides and phospholipids, appear to be altered in
      cancerous compared to control tissue. Using a genetic classification approach,
      classification success rates of up to 89% accuracy were obtained, depending on
      the number of regions included in the model. The diagnostic potential and
      practical applications of IR spectroscopy in brain tumor diagnosis are discussed.

PMID- 14587071
TI  - Cisplatin adducts of d(CCTCTG*G*TCTCC).d(GGAGACCAGAGG) in aqueous solution by
      vibrational circular dichroism spectroscopy.
AB  - The vibrational circular dichroism (VCD) and IR absorption spectra of a dodecamer
      d(CCTCTGGTCTCC).d(GGAGACCAGAGG) coordinated with cisplatin are distinct compared
      to those of the dodecamer without cisplatin. Although the intensity of
      PO(2)/deoxyribose absorptions (1150-850 cm(-1)) increases noticeably relative to
      those of the carbonyl and ring deformations of the bases (1750-1500 cm(-1)), the
      VCD spectra differ to a much greater extent. Overlapping positive and negative
      bands can be assigned relatively easily to individual vibrational modes. The
      effect of platination on the dodecamer duplex is expressed most prominently in
      VCD arising solely from the vibrations of the guanines bound to the platinum
      atom. The effect on the VCD features of other bases leads to minute wavenumber
      shifts at most. These observations are in agreement with previous NMR and X-ray
      experiments on the same oligonucleotide. The assignment of the absorption and VCD
      bands strongly resembles those of the octamer duplex d(CCTGGTCC).d(GGACCAGG) when
      coordinated with platinum. The spectra of the dodecamer did not indicate any
      isomerization of the complex with time, as is clearly the case for the octamer.

PMID- 14587072
TI  - Individual tyrosine side-chain contributions to circular dichroism of
      ribonuclease.
AB  - Experimental and theoretical studies using site-directed mutants of ribonuclease
      A (RNase A) offer more extensive information on the tyrosine side-chain
      contributions to the circular dichroism (CD) of the enzyme. Bovine pancreatic
      RNase A has three exposed tyrosine residues (Tyr73, Tyr76, and Tyr115) and three
      buried tyrosine residues (Tyr25, Tyr92 and Tyr97). The difference CD spectra
      between the wild type and the mutants at pH 7.0 (Deltaepsilon(277,wt) -
      Deltaepsilon(277,mut)) show bands with more negative DeltaDeltaepsilon(277)
      values for Y73F and Y115F than those for Y25F and Y92F and bands with positive
      DeltaDeltaepsilon(277) values for Y76F and Y97F. The theoretical calculations are
      in good semiquantitative agreement for all the mutants. The pH difference
      spectrum (pH 11.3-7.0) for the wild type shows a negative band at 295 nm and an
      enhanced positive band at 245 nm. The three mutants at buried tyrosine sites and
      one mutant at an exposed tyrosine site (Y76F) exhibit pH-difference spectra that
      are similar to that of the wild type. In contrast, two mutants at exposed
      tyrosine sites (Y73F and Y115F) exhibit diminished 295-nm negative bands and,
      instead of positive bands at 245 nm, negative bands are observed. Our results
      indicate that Tyr73 and Tyr115, two of the exposed tyrosine residues, are the
      largest contributors to the 277- and 245-nm CD bands of RNaseA, but the buried
      tyrosine residues and the one remaining exposed residue also contribute to these
      bands. Disulfide contributions to the 277- and 240-nm bands and the peptide
      contribution to the 240-nm band are confirmed theoretically.

PMID- 14587073
TI  - Structural changes of low density lipoproteins with Cu2+ and glucose induced
      oxidation.
AB  - The compositional and structural changes of lipids and apolipoproteins during in
      vitro oxidation of low density lipoprotein (LDL) are investigated in this study
      by IR spectroscopy. For comparison, LDL samples containing either copper or
      glucose at physiological or pathological concentrations are considered in order
      to know the separate affects of these chemical factors on LDL oxidation. The
      results show that the initial steps of lipid oxidation proceed through hydrogen
      atom loss from methylene groups, as well as loss of cholesteryl ester molecules,
      and later a recovering of carbonyl compounds resulting from aldehyde formation
      that generally occurs in autooxidation processes. Lipid oxidation is induced by
      copper ions, and glucose enhances metal ion induced LDL oxidation as determined
      by conjugated diene formation. As to the protein conformational changes, IR
      spectroscopy reveals for the first time that LDL oxidation involves formation of
      beta-sheet structures, these being more abundant in LDL samples with pathological
      concentrations of glucose or copper. Consequently, the LDL structural changes may
      contribute to the recognition of oxidized LDL particles by scavenger receptors.

PMID- 14587074
TI  - Determination of parathion residues in rice samples using a flow injection
      chemiluminescence method.
AB  - A sensitive flow injection chemiluminescence method is described for the
      determination of parathion pesticide, based upon its direct chemiluminescence
      reaction with luminol and hydrogen peroxide in the presence of non-ionic
      surfactant polyethylene glycol 400. Under the selected experimental conditions,
      the concentration of parathion is proportional to the CL intensity in the range
      0.02-1.0 mg/L. The detection limit was 0.008 mg/L and the relative standard
      deviation was 2.8% for 0.2 mg/L parathion solution (n = 11). This method was
      successfully applied to the determination of parathion residue in rice samples.

PMID- 14587075
TI  - Optimization of peroxynitrite-luminol chemiluminescence system for detecting
      peroxynitrite in cell culture solution exposed to carbon disulphide.
AB  - We established a peroxynitrite-luminol chemiluminescence system for detecting
      peroxynitrite in cell culture solution exposed to carbon disulphide (CS(2)).
      Three factors, including exposure time to ozone (Factor A), volume of
      peroxynitrite (ONOO(-)) solution (Factor B) and luminol concentrations (Factor C)
      at three levels were selected and the combinations were in accordance with
      orthogonal design L(9) (3(4)). Peroxynitrite was generated from the reaction of
      ozone and 0.01 mol/L sodium azide (NaN(3)) dissolved in carbonic acid buffer
      solution (pH 11), and it was reacted with luminol to yield chemiluminescence. The
      peak value, peak time and kinetic curve of the light emission were observed. The
      selected combination conditions were 50 s ozone, 800 micro L peroxynitrite and
      0.001 mol/L luminol solution. Cell culture solution with CS(2) enhanced the
      emission intensity of chemiluminescence (F = 8.38, p = 0.018) and shortened the
      peak time to chemiluminescence (F = 139.00, p = 0.0001). The data demonstrated
      that this luminol chemiluminescence system is suitable for detecting
      peroxynitrite in cell culture solutions for evaluating the effect of CS(2) on
      endothelial cells.

PMID- 14587076
TI  - Use of ATP bioluminescence to determine the bacterial sensitivity threshold to a
      bacteriocin.
AB  - A new ATP bioluminescence-based method was developed to determine the
      effectiveness of nisin on a sensitive strain of Lactococcus cremoris. The
      principle of the method is to quantify the release of adenylic-nucleotides (AN)
      by a sensitive strain under the action of the bacteriocin, with the complex
      luciferin-luciferase. Nisin-induced leakage of AN included ATP from a sensitive
      L. cremoris to the external medium immediately after the contact with the
      bacteria. The growth of L. cremoris was correlated with the extracellular AN
      content. The extracellular ATP and AN concentration exhibited a linear
      correlation to the logarithm of the nisin concentration. For the determination of
      the effectiveness threshold, the concentration of AN was more sensitive and more
      reliable than the direct quantification of ATP. The effectiveness threshold,
      corresponding to a 100% inhibition of L. cremoris growth, was obtained for a null
      concentration of intracellular nucleotides, i.e. for a AN(tot):AN(ext) ratio = 1.
      For an initial concentration of 1.4 x 10(7) bacteria/mL, the nisin effectiveness
      threshold is 3.4 +/- 0.01 mg nisin/L. It is possible to detect effectiveness
      threshold concentration by taking into account the physiological state of the
      cells.

PMID- 14587078
TI  - Validation of different chemilumigenic substrates for detecting extracellular
      generation of reactive oxygen species by phagocytes and endothelial cells.
AB  - Chemiluminescence is a widely used tool to detect extracellular generation of
      reactive oxygen species (ROS). In the present study we tested four different
      chemilumigenic substrates (CLS)--luminol, isoluminol, lucigenin and pholasin-to
      detect extracellular CL in different cell types: polymorphonuclear leukocytes
      (PMN); DMSO-differentiated HL-60 cells; murine macrophages (RAW 264.7); and TNF
      alpha-stimulated human endothelial cells (HUVEC). Extracellular ROS production
      was calculated by subtracting intracellular CL response in the presence of
      superoxide dismutase and catalase from the overall CL response in the absence of
      enzymes. CL varied considerably in dependence on the CLS and the stimulus used to
      evoke ROS generation. Luminol (oxidized LDL and zymosan stimulation) and
      isoluminol (FMLP and PMA stimulation) were the most effective CLS for PMN. Using
      5 micromol/L lucigenin as CLS, small but consistent CL responses could be
      obtained in macrophages stimulated with PMA, zymosan or oxidized LDL. FMLP
      stimulated extracellular CL in H-60 cells, HUVEC and macrophages was detected
      with the greatest sensitivity by pholasin. Our results demonstrate that none of
      the investigated CLS consistently yielded the highest CL quantum, either in
      different cell types with one stimulating agent or by different stimulating
      agents in one cell type. To get the highest CL quantum in experimental studies,
      we recommend optimizing the CLS depending on the cell type and the ROS-generating
      stimulus used.

PMID- 14587077
TI  - Kinetic simulation studies on the transient formation of the oxo-iron(IV)
      porphyrin radical cation during the reaction of iron(III) tetrakis-5,10,15,20-(N
      methyl-4-pyridyl)-porphyrin with hydrogen peroxide in aqueous solution.
AB  - High-valent oxo-iron(IV) species are commonly proposed as the key intermediates
      in the catalytic mechanisms of iron enzymes. Water-soluble iron(III) tetrakis
      5,10,15,20-(N-methyl-4-pyridyl)porphyrin (Fe(III)TMPyP) has been used as a model
      of heme-enzyme to catalyse the hydrogen peroxide (H(2)O(2)) oxidation of various
      organic compounds. However, the mechanism of the reaction of Fe(III)TMPyP with
      H(2)O(2) has not been fully established. In this study, we have explored the
      kinetic simulation of the reaction of Fe(III)TMPyP with H(2)O(2) and of the
      catalytic reactivity of FeTMPyP in the luminescent peroxidation of luminol.
      According to the mechanism that has been established in this work, Fe(III)TMPyP
      is oxidized by H(2)O(2) to produce (TMPyP)(*+)Fe(IV)[double bond]O (k1 = 4.5 x
      10(4)/mol/L/s) as a precursor of TMPyPFe(IV)[double bond]O. The intermediate,
      (TMPyP)(*+)Fe(IV)[double bond]O, represented nearly 2% of Fe(III)TMPyP but it
      does not accumulate in sufficient concentration to be detected because its decay
      rate is too fast. Kinetic simulations showed that the proposed scheme is capable
      of reproducing the observed time courses of FeTMPyP in various oxidation states
      and the decay profiles of the luminol chemiluminescence. It also shows that
      (TMPyP)(*+)Fe(IV)[double bond]O is 100 times more reactive than
      TMPyPFe(IV)[double bond]O in most of the reactions. These two species are
      responsible for the initial sharp and the sustained luminol emissions,
      respectively.

PMID- 14587079
TI  - In vivo monitoring of chlorophyll fluorescence response to low-dose gamma
      irradiation in pumpkin (cucurbita pepo) leaves.
AB  - The effect of gamma-irradiation on the in vivo-measured chlorophyll fluorescence
      in a pumpkin leaves (Cucurbita pepo) has been investigated. Plants were grown in
      the same environment, then divided into several groups and irradiated at ambient
      conditions at small dose levels (up to 13.4 Gy) with (60)Co gamma-rays. The post
      irradiation effect on chlorophyll status in the leaves was examined by measuring
      chlorophyll fluorescence 2 days (48 h) after exposure. It is undoubtedly found
      that the value of fluorescence intensity ratio (FIR) at 690 nm and 735 nm
      (F(690)/F(735)) depends upon the ionizing radiation dose. Even with the smallest
      dose of 3.35 Gy, ionizing radiation notably altered the fluorescence spectra of
      leaves. The spectra difference was manifested by decrease of FIR due to changed
      chlorophyll luminescence, the possible reason for which could be increase of
      chlorophyll concentration during the recovery process of the plant. The potential
      implications of these results for plant physiological status monitoring, as well
      as for pollution detection and assessment, are discussed in brief.

PMID- 14587081
TI  - Bibliography. Luminescence literature. Chemiluminescent and bioluminescent
      immunoassays.

PMID- 14587080
TI  - The acute response of neutrophil function to a bout of judo training.
AB  - Intensive exercise training decreases neutrophil functions in athletes. However,
      no studies to date have investigated the effect of irregular-interval training,
      such as is associated with judo training programmes, on neutrophil functions. The
      purpose of this study was to examine such effects. Thirty-seven male college
      judoists participated in this study. Neutrophil oxidative burst activity,
      phagocytic activity and expression of CD11b and CD16 per cell were measured by fl
      ow cytometry before and after judo training. Total neutrophil counts increased
      significantly from 2.98 +/- 0.82 to 7.95 +/- 1.80 x 10(3)/ microL (p < 0.001).
      The proportion of neutrophils producing reactive oxygen species (ROS) was
      increased significantly (p < 0.001). On the other hand, the phagocytic activity
      decreased after training, as shown by a decrease in the amount of ingested
      opsonized zymosan per cell (p < 0.001), possibly as a compensatory effect for the
      increased numbers of ROS-producing neutrophils. Expression of CD11b and CD16 per
      cell decreased by 20% and 30%, respectively, after judo training. In conclusion,
      judo training induced a decrease in phagocytic activity through the lowered
      expression of CD11b and CD16 on the surface of neutrophils, and increased the
      oxidative burst activity of neutrophils.

PMID- 14587082
TI  - Fragmentation pathways of sulphonamides under electrospray tandem mass
      spectrometric conditions.
AB  - Sulphonamides are antibacterial compounds used extensively in farming and
      veterinary practice. Residues are commonly found in meat and milk. The growing
      concern about antibiotic resistance of bacteria led to a lowering of the legal
      concentration limits of sulphonamides in food. A range of analytical methods,
      employing tandem mass spectrometry (MS/MS) and selected reaction monitoring
      (SRM), have been developed to allow screening at the limit of detection (LOD)
      levels. Interest was drawn to the fragment ions produced by the sulphonamides,
      some involving complex rearrangements that have not previously been looked at.
      Here we report an investigation into the fragmentation pattern of sulphonamides
      under electrospray (ES) MS/MS conditions using ion trap and Fourier transform ion
      cyclotron resonance (FTICR) mass spectrometers. Structures are proposed for the
      main fragment ions observed for a range of sulphonamides, the effects of the
      functional groups in the dissociation pathway of the compounds are investigated,
      and the mechanisms leading to the main fragment ions are explored.

PMID- 14587083
TI  - A new deuterated alkylating agent for quantitative proteomics.
AB  - Weakly basic molecules containing a double bond, such as 2- and 4-vinylpyridine,
      are able to react and selectively alkylate -SH groups in proteins, thus
      preventing their re-oxidation to disulphide bridges. In contrast to conventional
      alkylating agents such as iodoacetamide and non-charged acrylamide derivatives,
      such molecules achieve 100% alkylation of all -SH residues, even in complex
      proteins, without reacting with other functional groups. Their use is
      particularly effective in proteome analysis and more generally for analyzing
      proteins in which the -SH groups should be blocked. Additionally, the use of
      vinylpyridines, partially or totally deuterated and thus with a mass difference
      compared with their non-deuterated counterparts of 4-7 Da, allows studies of
      induction/repression of protein synthesis (quantitative proteomics).

PMID- 14587084
TI  - Use of different proteases working in acidic conditions to improve sequence
      coverage and resolution in hydrogen/deuterium exchange of large proteins.
AB  - The combination of hydrogen exchange and mass spectrometry has been widely used
      in structural biology, providing views on protein structure and protein dynamics.
      One of the constraints is to use proteases working at low pH and low temperature
      to limit back-exchange during proteolysis. Although pepsin works in these
      conditions and is currently used in such experiments, sequence coverage is not
      always complete especially for large proteins, and the spatial resolution of the
      exchange rate is limited by the size of the resulting peptides. In this study we
      tried two other proteases, protease type XIII from Aspergillus saitoi and
      protease type XVIII from Rhizhopus species. The penicillin-binding protein X (PBP
      2X*), a 77-kDa protein, was selected as a model. Like pepsin, neither of these
      proteases is really specific, but we found very good reproducibility in the
      digestion pattern. Compared with using pepsin alone, combining the results of the
      three independent proteolyses increased the coverage for the peptide mapping,
      thus avoiding missing some potentially interesting regions of the protein.
      Furthermore, we obtained a better spatial resolution for deuterium incorporation
      data, specifying accurately the deuterated regions.

PMID- 14587085
TI  - Development of a method for the direct analysis of peptide AM336 in monkey
      cerebrospinal fluid using liquid chromatography/electrospray ionization mass
      spectrometry with a mixed-function column.
AB  - A liquid chromatography/mass spectrometry (LC/MS) analytical procedure, using a
      single column for sample clean-up, enrichment and separation, has been developed
      for the determination of the peptide AM336 in monkey cerebrospinal fluid (CSF).
      CSF samples were injected and analyzed using a polymer-coated mixed-function high
      performance liquid chromatography (HPLC) column with gradient elution and
      application of a timed valve-switching event. The mass spectrometer was operated
      in the positive electrospray ionization (ESI(+)) mode with single ion recording
      (SIR) at m/z 920. The method was validated, yielding calibration curves with
      correlation coefficients greater than 0.9892. Assay precision and accuracy were
      evaluated by direct injection of AM336-fortified CSF samples at three
      concentration levels. Analyzed concentrations ranged from 99.93 to 113.1% of
      their respective theoretical concentrations with coefficients of variation below
      9.0%. An evaluation of the signal-to-noise (S/N) ratio for a 200 ng/mL
      calibration standard, considered to be the lower limit of quantitation (LLOQ),
      resulted in an estimated limit of detection (LOD) of 31.2 ng/mL. Preliminary data
      suggest the possibility of using this method to analyze AM336 also in plasma
      samples, pending the successful outcome of additional investigations.

PMID- 14587086
TI  - Comparing differentiation of xylene isomers by electronic ionization, chemical
      ionization and self-ion/molecule reactions and the first observation of methyne
      addition ions for xylene isomers in self-ion/molecule reactions for non
      nitrogenated compounds.
AB  - This study presents the self-ion/molecule reaction (SIMR) spectra of three xylene
      isomers, and proposes an approach to differentiating them based on observed
      differences in relative abundances of ions formed by SIMR in an internal source
      ion trap instrument. It also demonstrates the applicability of SIMR for isomer
      discrimination, which is better than electron ionization (EI) and dimethyl ether
      chemical ionization (DME CI) in an ion trap mass spectrometer (ITMS) since no CI
      reagent, metal ions or internal standards are required to perform SIMR. The
      merits of the new method for distinguishing isomers are that it is simple, rapid
      and economic. To date, methyne addition products ([M+13](+) ions) have been
      observed for several nitrogenated compounds including aza-crown ethers, aniline
      and dopamine from SIMR in the ITMS. The xylene isomers are, however, the first
      three non-nitrogenated compounds that have been shown to produce the methyne
      addition ions in SIMR.

PMID- 14587087
TI  - Detection of peonidin and pelargonidin glycosides in black carrots (Daucus carota
      ssp. sativus var. atrorubens Alef.) by high-performance liquid
      chromatography/electrospray ionization mass spectrometry.
AB  - Anthocyanins of black carrots (Daucus carota ssp. sativus var. atrorubens Alef.)
      were investigated by high-performance liquid chromatography/electrospray
      ionization mass spectrometry. Besides the main compounds which have already been
      characterized in detail as cyanidin glycosides, six anthocyanins with m/z 757,
      565, 595, 903, 933 and 903 were detected and unambiguously characterized as
      peonidin and pelargonidin glycosides, based on their fragmentation patterns.
      Peonidin and pelargonidin were identified after acid hydrolysis by comparison of
      the fragmentation patterns and retention times of the released aglycones with
      those of standard compounds. To the best of our knowledge this is the first
      report on anthocyanins in black carrots consisting of aglycones other than
      cyanidin.

PMID- 14587088
TI  - Collection of selected reaction monitoring and full scan data on a time scale
      suitable for target compound quantitative analysis by liquid
      chromatography/tandem mass spectrometry.
AB  - A hybrid linear ion trap/triple quadrupole mass spectrometer was used to
      demonstrate the value of collecting full scan qualitative data during
      quantitative analysis of target compounds. We present examples of the additional
      information that can be obtained from plasma samples analyzed primarily for
      target compound concentrations. This information includes detection of
      circulating metabolites, dosing vehicle, interfering matrix components, and
      potential interfering drug conjugates. Additionally, the quantitative results
      from selected reaction monitoring (SRM) analysis and from combined full scan and
      SRM analysis (SRM/EMS) were compared. The quantitative data in both scan modes
      are acceptable in terms of sensitivity, accuracy and precision. One can conclude
      from this work that the hybrid linear ion trap/triple quadrupole mass analyzer
      can provide in a single analysis both useful qualitative data, and accurate and
      precise quantitative data from the samples routinely prepared and analyzed for
      target drug concentrations.

PMID- 14587089
TI  - Atmospheric pressure photoionization mechanisms. 2. The case of benzene and
      toluene.
AB  - Benzene and toluene have been proposed previously as dopants in atmospheric
      pressure photoionization (APPI) experiments on compounds exhibiting ionization
      energies higher than the energy of photons used for irradiation. Their low
      ionization energies lead to their easy photoionization and the ions so formed
      lead to the ionization of analytes through charge exchange. However, some
      measurements have shown that some protonation reactions also take place, and a
      series of experiments was undertaken to investigate this unexpected behavior. It
      was shown that, when benzene is irradiated in the APPI source, the odd-electron
      molecular ions of phenol, diphenyl ether and phenoxyphenol are produced in high
      yield, together with protonated diphenyl ether and protonated phenoxyphenol.
      These results have been confirmed by deuterium labelling and MS(n) experiments. A
      possible mechanism is proposed, based on a radical attack by benzene molecular
      ions on oxygen molecules present inside the APPI source, analogous to that
      proposed in the literature for phenyl radicals. Similar results have been
      obtained with toluene, proving that APPI is able to activate a series of
      reactions leading to highly reactive species which are highly effective in
      promoting ionization of molecules with ionization energies higher than the photon
      energy.

PMID- 14587090
TI  - Parallel determination of multiple protein metabolite interactions using cell
      extract, protein microarrays and mass spectrometric detection.
AB  - Analysis of interactive networks between proteins and other molecular
      constituents is of paramount importance to delineate complex cellular processes.
      In order to facilitate this process, new technologies that allow rapid, high
      throughput parallel screening, as well as identification of constituents, are
      necessary. A particularly powerful combination in this regard could be the use of
      multiprotein microarrays coupled with mass spectrometry (MS). In the initial step
      of the method development we applied MS to single-protein microarrays. We
      demonstrated that even a simplified version of the method allows rapid parallel
      label-free assay of specific protein interactions with multiple metabolites
      derived from complex artificial and natural mixtures. The microarrays fabricated
      by the electrospray deposition technique and cross-linked in glutaraldehyde vapor
      were brought into contact with droplets of solution containing either a natural
      extract of baker's yeast cells or an artificial cocktail of metabolites. After
      washing, the microarrays were placed into 75% methanol to denature proteins and
      release specifically bound metabolites. The eluates were then analyzed by
      electrospray ionization mass spectrometry (ESI-MS) to simultaneously detect all
      the metabolites bound. Such a procedure applied to ten different proteins
      demonstrated that 50-400 ng of cross-linked protein is enough to obtain ion
      intensities from metabolites that are well distinguishable above noise. The
      compatibility of microplates and different microarray designs with MS detection
      is discussed.

PMID- 14587092
TI  - Post-gel permeation chromatography polymer blend analysis from a raster-deposited
      matrix-assisted laser desorption/ionization target.

PMID- 14587091
TI  - Increasing sensitivity and decreasing spot size using an inexpensive, removable
      hydrophobic coating for matrix-assisted laser desorption/ionisation plates.
AB  - Spot size reduction and increased detection sensitivity in matrix-assisted laser
      desorption/ionisation (MALDI) of small molecules are accomplished by using an
      inexpensive and removable hydrophobic coating for MALDI targets, based on 3M
      Scotch Gard surface treatment. Several variations in sample preparation were
      explored, such as surface coating technique, identity of the matrix, solvent
      composition, and the type of metal support plate used. These were investigated on
      both uncoated and coated surfaces and their impact on spot size, crystal
      coverage, and sensitivity is presented here. Additionally, crystallisation
      behaviour obtained on coated plates is compared with that on uncoated plates
      using scanning electron microscope analysis. To demonstrate the potential of the
      new coating technique, erythromycin A and valinomycin are studied to determine
      the increase in detection sensitivity of coated plates in comparison to uncoated
      plates, and to reveal the suitability of the plates for application in combined
      high-performance liquid chromatography/MALDI (HPLC/MALDI), where widely varying
      solvent compositions and droplet volumes are observed. It is shown that
      enhancements in detection sensitivities correlate very well with the achieved
      spot size reduction. The versatility of the coated plates is also exhibited by
      the ease of removing the surface layer, after which the plates can be rigorously
      cleaned without worry about damaging the hydrophobic surface, followed by a quick
      reapplication of new hydrophobic coating material. This makes the non-polar
      coating superior to more expensive commercial hydrophobic-coated targets, which
      are much more delicate to clean. Furthermore, cleaning and reapplication
      eliminate potential carry-over effects and the easy application procedure also
      makes the fabrication of inexpensive, disposable MALDI targets readily possible.

PMID- 14587093
TI  - Atmospheric pressure chemical ionisation liquid chromatography/multi-stage mass
      spectrometry of isobaric bacteriophaeophorbide d methyl esters.

PMID- 14587094
TI  - Comparative genomic hybridization of estrogen-induced ectopic uterine-like stem
      cell neoplasms in the hamster kidney: nonrandom chromosomal alterations.
AB  - Karyotype and comparative genomic hybridization (CGH) analyses were performed to
      identify nonrandom/consistent chromosomal alterations in solely estrogen (E)
      induced primary ectopic uterine-like stem cell tumors in the kidney (EULTK) of
      the Syrian hamster, using a criterion of >/=20% frequency for nonrandom
      occurrence. Employing this criterion, EULTK karyotype analysis showed consistent
      gains in chromosomes 3, 6, 11, 14, 16, 20, and 21. Consistent trisomies were seen
      in all of these nonrandomly gained chromosomes. Only chromosomes 3 and 6
      exhibited appreciable tetrasomies. Chromosome losses were observed consistently
      in chromosomes 7, 12, 17, and 19. Employing the same criterion, CGH analysis of
      primary EULTKs showed nonrandom amplified sequences at 1pa1-a4, 2cen-pter, 3pa1
      a4, 6qb2-b4, 20qa1-a4, 21qa1-a2, Xqa3-qter and regional consistent losses at 1qc1
      qter, 2qb1-c1, 3qa2-a7, 11qb5-qter, 15qa2-a5, 18qa2-a4, and 21pa. Moreover, 88%
      of the EULTKs examined exhibited amplification of the 6qb2-b4 region, where c-myc
      resides. The data presented lend credence to the supposition that chromosomal
      instability (CIN) is elicited by the upstream overexpression and subsequent
      amplification of c-myc by Es in multipotential interstitial uterine stem cells
      present in the kidney, thus leading to neoplastic development.

PMID- 14587095
TI  - Cell growth inhibition by all-trans retinoic acid in SKBR-3 breast cancer cells:
      involvement of protein kinase Calpha and extracellular signal-regulated kinase
      mitogen-activated protein kinase.
AB  - All-trans retinoic acid (ATRA), a synthetic derivative of vitamin A, inhibits the
      growth of breast cancer cells. To elucidate the mechanism by which ATRA causes
      cell growth inhibition, we examined changes in cell cycle and intracellular
      signaling pathways, focusing on protein kinase C (PKC) and mitogen-activated
      protein kinase (MAPK). Using the estrogen receptor-negative, retinoid receptor
      positive breast cancer cell line SKRB-3, we found that treatment with ATRA
      significantly decreased the expression of PKCalpha, as well as reducing ERK MAPK
      phosphorylation. ATRA treatment leads to dephosphorylation of Rb, and
      consequently to G(1) arrest. Marked changes in the expression of cyclins
      (particularly cyclins A and E) were observed in SKBR-3 cells treated with ATRA.
      Using a series of pharmacological and molecular approaches, we found evidence
      that ATRA-induced SKBR-3 cell growth inhibition involves the deregulation of the
      PKCalpha-MAPK pathway. These data suggest that retinoids interfered with signal
      transduction pathways that are crucial for cell cycle progression, and highlight
      the complexities of the biological effects of retinoid derivatives.

PMID- 14587096
TI  - Tnfa and Il-10 deficiencies have contrasting effects on lung tumor
      susceptibility: gender-dependent modulation of IL-10 haploinsufficiency.
AB  - Epidemiologic evidence suggests that pulmonary diseases with a prominent chronic
      inflammatory component elevate lung cancer risk. Genetic manipulations of mouse
      models of lung inflammation and tumorigenesis can be used to investigate this
      association. The genes encoding pro-inflammatory tumor necrosis factor-alpha
      (TNFalpha) and antiinflammatory IL-10 cytokines map within quantitative trait
      loci that regulate susceptibility to lung tumor development in mice; sensitive
      A/J and resistant C57BL/6J (B6) mice have different Tnfa and Il-10 alleles.
      Genetic ablation studies were performed to examine whether these genes would
      qualify as candidate tumor modifiers. Tnfa null (-/-) mice on a B6 background and
      B6.129 Il-10(-/-) mice were intercrossed with A/J mice and subjected to urethane
      carcinogenesis; lung tumor multiplicity was determined 20 weeks later. In the
      absence of one copy of Tnfa, tumor number. Male Il-10(+/+) mice developed more
      tumors than did female mice (P < 0.001), absence of one copy of Il-10 raised
      tumor number in female mice to that observed in +/+ males, but no change in
      multiplicity occurred in Il-10 hemizygous males. Thus, a deficit of pro
      inflammatory TNFalpha decreased the number of tumors, whereas diminished gene
      copy number of anti-inflammatory IL-10 increased tumorigenesis; manifestation of
      an effect of Il-10 haploinsufficiency is gender dependent. These studies support
      a role for inflammation in lung cancer susceptibility.

PMID- 14587097
TI  - Reduced transcription of the RB2/p130 gene in human lung cancer.
AB  - Reduced expression of the retinoblastoma gene (RB)2/p130 protein, as well as
      mutation of exons 19, 20, 21, and 22 of the same gene, has been reported in
      primary lung cancer. However, it has been suggested by other investigators that
      mutational inactivation and loss of the RB2/p130 gene and protein, respectively,
      are rare events in lung cancer. In order to determine the contribution and
      mechanisms of RB2/p130 gene inactivation to lung cancer development and
      progression, we quantified RB2/p130 mRNA expression levels in a range of human
      lung cancer cell lines (n = 13) by real-time reverse transcription (RT)
      polymerase chain reaction (PCR) analysis. In comparison to normal lung tissue,
      reduced transcription of the RB2/p130 gene was found in all small cell lung
      cancer cell lines examined, along with six out of the eight nonsmall cell lung
      cancers tested, most of which had inactivation of RB/p16 pathway. On the basis of
      Western blot analysis, the expression of RB2/p130 protein was consistent with RNA
      expression levels in all lung cancer cell lines examined. In addition, the
      mutational status of the RB2/p130 gene (specifically, exons 19, 20, 21, and 22)
      was determined in 30 primary lung cancers (from patients with distant metastasis)
      and 30 lung cancer cell lines by PCR-single strand conformation polymorphism
      (SSCP) analysis and direct DNA sequencing. There was no evidence of somatic
      mutations within the RB2/p130 gene in the 60 lung cancer samples (both cell lines
      and tumors) assessed, including the 11 lung cancer cell lines that displayed
      reduced expression of the gene. Furthermore, hypermethylation of the RB2/p130
      promoter was not found in any of the above-mentioned 11 cell lines, as determined
      by a DNA methylation assay, combined bisulfite restriction analysis (COBRA). The
      results of the present study suggest that the reduced RB2/p130 expression seen in
      lung cancer may be in part transcriptionally mediated, albeit not likely via a
      mechanism involving hypermethylation of the RB2/p130 promoter. The observed
      reduction in RB2/p130 gene expression may be due to histone deacetylation,
      altered mRNA stability, and/or other forms of transcriptional regulation.

PMID- 14587098
TI  - Elevated levels of prostate-specific antigen (PSA) in prostate cancer cells
      expressing mutant p53 is associated with tumor metastasis.
AB  - The underlying basis for rising levels of prostate-specific antigen (PSA) in
      prostate cancer is not fully understood, but attention has turned to the
      possibility that loss of normal p53 function might be directly involved. We have
      investigated the relationship between p53 function and PSA expression using in
      vitro and in vivo approaches. Three prostate cancer-derived p53 mutants (F134L,
      M237L, R273H) were introduced into LNCaP prostate cancer cells and stable
      transfectants established. Expression of mutant p53 was demonstrated by Western
      blot analysis, inactivation of wtp53 function, and a loss of p53-dependent
      responses to DNA damage induced by UV-irradiation and cisplatin. Levels of PSA
      mRNA and secreted protein were determined by RT-PCR and Western blotting,
      respectively. Serine protease activity was assessed using an esterase assay. In
      vivo effects of mutant p53 expression were examined after orthotopic implantation
      into prostates of nude mice. Expression of all p53 mutants was associated with
      elevated PSA mRNA and secreted PSA protein. In a representative line, mutant p53
      was also associated with increased PSA protease-like activity compared with a
      control line expressing wildtype p53. Overall PSA levels, and PSA levels in serum
      from mice bearing tumors derived from cells expressing mutant p53, were increased
      compared with levels in mice bearing tumors derived from control cells. In
      addition, the tumors derived from cells with mutant p53 had increased
      vascularization and induced lymph node metastases. These data provide in vitro
      and in vivo support for the notion that p53 mutations directly contribute to
      increased levels of serum PSA, and are associated with more aggressive tumors.

PMID- 14587099
TI  - Changes in gene expression during chemical-induced nephrocarcinogenicity in the
      Eker rat.
AB  - Hydroquinone (HQ) is a rodent carcinogen and a potential human carcinogen.
      Glutathione conjugation of HQ enhances its biological reactivity, and 2,3,5-tris
      (glutathion-S-yl)hydroquinone (TGHQ) is a potent nephrotoxicant and
      nephrocarcinogen in the Eker rat. Moreover, a single exposure of primary
      epithelial cells derived from Eker rat kidneys to TGHQ transforms these cells
      into an immortalized phenotype (quinol-thioether transformed rat renal epithelial
      (QT-RRE) cells). The Eker rat bears a mutation in one allele of the tuberous
      sclerosis-2 (Tsc-2) tumor suppressor gene, which predisposes the animals to the
      development of spontaneous and chemical-induced renal cell carcinoma. Thus, the
      Eker rat provides a unique model for elucidating the mechanisms of renal tubular
      epithelial carcinogeneisis. cDNA microarray analysis of QT-RRE3 cells and of
      tumor tissue derived from the kidneys of Eker rats treated with TGHQ revealed
      alterations (by threefold or greater) in the expression of a total of 80 genes.
      Fifteen percent of these genes exhibited similar expression patterns in both QT
      RRE cells and tumor tissue. The differentially expressed genes primarily
      participate in three major areas: (1) signal transduction or in the regulation of
      signal transduction (extracellular signal regulated kinase 2 (ERK2); protein
      kinase CK2; protein kinase B; c-jun; NF-kappaB; ras-related GTPases; annexins),
      (2) stress response, tissue remodeling, and DNA repair (glutathione-S
      transferases; procollagen c proteinase enhancer; plasminogen activator; tissue
      inhibitor of metalloprotease 3; apurinic/apyrimidic endonuclease), and (3)
      electron transport and energy homeostasis (cytochrome c oxidase subunits). The
      changes in the expression of many of these genes was confirmed by reverse
      transcription (RT)-polymerase chain reactions (PCR) using primers specific for
      the differentially expressed genes. As an example, the annexin I and II genes,
      implicated in signal transduction, were highly induced in tumor tissue and also
      in dysplastic lesions isolated from the kidneys of rats treated chronically with
      TGHQ. The annexin I and II proteins were also upregulated in tumor tissue, which
      probably play an important role in TGHQ-induced nephrocarcinogenesis. Moreover,
      in the present study, a tumorigenicity assay using athymic nude mice revealed
      that QT-RRE cell lines formed tumors when injected in the subcutis of nude mice,
      providing evidence that the cells are malignantly transformed. Histopathological
      analysis further indicated that the tumors were composed of neoplastic cells,
      resembling renal carcinoma cells with varying degrees of atypia, with the
      presence of apoptotic and mitotic figures.

PMID- 14587100
TI  - Role of antioxidant enzymatic defences against oxidative stress H(2)O(2) and the
      acquisition of oxidative tolerance in Candida albicans.
AB  - In Candida albicans, trehalose plays an essential role as a protector of cell
      integrity against oxidative challenge. A double homozygous mutant, tps1/tps1,
      deficient in trehalose synthesis, displayed severe cell mortality when exposed to
      high H(2)O(2) concentrations, compared with its congenic parental (CAI-4) strain
      (Alvarez-Peral et al., 2002). We have examined the putative role of a set of well
      known antioxidant enzymes as components of the defence mechanism against
      oxidative challenges. When exposed to mild non-lethal oxidative treatment (0.5 mM
      H(2)O(2)), a significant induction of catalase, glutathione reductase (GR), and
      Cu,Zn-superoxide dismutase (SOD) was recorded in tps1/tps1 exponential cultures.
      However, in CAI-4 cells, subjected to the same conditions, there was only a clear
      activation of catalase, Mn-SOD and Cu,Zn-SOD activities. The degree of activation
      was always much more pronounced in the trehalose-deficient mutant than in its
      wild-type counterpart, except for Mn-SOD activity. After exposure to severe
      oxidative stress (50 mM H(2)O(2)) only GR and catalase activities increased in
      tps1/tps1 cultures, whereas in CAI-4 cells GR but not catalase was induced. In
      both cell strains, 50 mM H(2)O(2) caused inhibition of the Mn- and Cu,Zn-SOD
      isozymes, this inhibition being more pronounced in tps1/tps1 cells. C. albicans
      is able to acquire adaptive oxidative tolerance by pretreatment with a low non
      stressing concentration of H(2)O(2) before exposure to a drastic oxidative
      challenge. When these antioxidant activities were measured during the adaptive
      response, a greater degree of enzymatic antioxidant induction was consistently
      observed in the tps1/tps1 mutant with respect to the CAI-4 strain. Together with
      a higher intrinsic sensitivity of tps1/tps1 cells, we suggest that this
      unexpected increase might be explained in terms of a compensatory mechanism to
      overcome the lack of endogenous trehalose upon drastic oxidative exposure,
      although this induction was not sufficient to improve the percentage of cell
      viability.

PMID- 14587101
TI  - LYS2 gene and its mutation in Kluyveromyces lactis.
AB  - The KlLYS2 gene, encoding the alpha-aminoadipate reductase of Kluyveromyces
      lactis, was isolated by complementation of a lysA1 mutant. The deduced amino acid
      sequence shared an identity of 73% with the LYS2 product of Saccharomyces
      cerevisiae. Despite the high sequence homology of the alpha-aminoadipate
      reductase genes, the two yeast species differently responded to the presence of
      alpha-aminoadipate in the medium. Wild-type S. cerevisiae is known to be
      sensitive to alpha-aminoadipate, but becomes resistant when mutated to lys2. In
      contrast, K. lactis strains were found to be naturally resistant to alpha
      aminoadipate. Therefore, the positive selection procedure for the isolation of
      lys2 mutants on alpha-aminoadipate, as practised in S. cerevisiae, cannot be
      applied to K. lactis. A possible reason of this difference may be that the
      catalytic rate of the alpha-aminoadipate reductase differs in the two yeasts. The
      EMBL/Genbank Accession No. for the KlLYS2 gene is AJ504405.

PMID- 14587103
TI  - Screening for new yeast mutants affected in mannosylphosphorylation of cell wall
      mannoproteins.
AB  - We have carried out a screen of 622 deletion strains generated during the EUROFAN
      B0 project to identify non-essential genes related to the mannosylphosphate
      content of the cell wall. By examining the affinity of the deletants for the
      cationic dye alcian blue and the ion exchanger QAE-Sephadex, we have selected 50
      strains. On the basis on their reactivity (blue colour intensity) in the alcian
      blue assay, mutants with a lower phosphate content than wild-type cells were then
      arranged in groups defined by previously characterized mutants, as follows: group
      I (mnn6), group II (between mnn6 and mnn9) and group III (mnn9). Similarly,
      strains that behaved like mnn1 (i.e. a blue colour deeper than wild-type) were
      included in group VI. To confirm the association between the phenotype and a
      specific mutation, strains were complemented with clones or subjected to tetrad
      analysis. Selected strains were further tested for extracellular invertase and
      exoglucanase. Within groups I, II and III, we found some genes known to be
      involved in oligosaccharide biosynthesis (ALG9, ALG12, HOC1), secretion (BRE5,
      COD4/COG5, VPS53), transcription (YOL072w/THP1, ELP2, STB1, SNF11), cell polarity
      (SEP7, RDG1), mitochondrial function (YFH1), cell metabolism, as well as orphan
      genes. Within group VI, we found genes involved in environmentally regulated
      transduction pathways (PAL2 and RIM20) as well as others with miscellaneous or
      unknown functions. We conclude that mannosylphosphorylation is severely impaired
      in some deletants deficient in specific glycosylation/secretion processes, but
      many other different pathways may also modulate the amount of mannosylphosphate
      in the cell wall.

PMID- 14587102
TI  - Negative regulation of phospholipid biosynthesis in Saccharomyces cerevisiae by a
      Candida albicans orthologue of OPI1.
AB  - Structural genes of phospholipid biosynthesis in the yeast Saccharomyces
      cerevisiae are coordinately regulated by a UAS element, designated ICRE
      (inositol/choline-responsive element). Opi1 is a negative regulator responsible
      for repression of ICRE-dependent genes in the presence of an excess of inositol
      and choline. Gene regulation by phospholipid precursors has been also reported
      for the pathogenic yeast Candida albicans. Screening of a data base containing
      raw sequences of the C. albicans genome project allowed us to identify an open
      reading frame exhibiting weak similarity to Opi1. Expression of the putative
      CaOPI1 in an opi1 mutant of S. cerevisiae could restore repression of an ICRE
      dependent reporter gene. Similar to OPI1, overexpression of CaOPI1 strongly
      inhibited derepression of ICRE-driven genes leading to inositol-requiring
      transformants. Previous work has shown that Opi1 mediates gene repression by
      interaction with the pleiotropic repressor Sin3. The genome of C. albicans also
      encodes a protein similar to Sin3 (CaSin3). By two-hybrid analyses and in vitro
      studies for protein-protein interaction we were able to show that CaOpi1 binds to
      ScSin3. ScOpi1 could also interact with CaSin3, while CaOpi1 failed to bind to
      CaSin3. Despite of some conservation of regulatory mechanisms between both
      yeasts, these results suggest that repression of phospholipid biosynthetic genes
      in C. albicans is mediated by a mechanism which does not involve recruitment of
      CaSin3 by CaOpi1.

PMID- 14587104
TI  - Analysis of the genetic variability in the species of the Saccharomyces sensu
      stricto complex.
AB  - Random amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR) analysis
      was applied to differentiate the sibling species Saccharomyces bayanus, S.
      cerevisiae, S. paradoxus and S. pastorianus, which constitute the most common
      strains of the Saccharomyces sensu stricto complex. Six decamer primers of
      arbitrary sequences were used to amplify the DNA of 58 strains. Species-specific
      (diagnostic) bands were obtained for each species. Two phylogenetic trees
      constructed by the neighbour-joining and maximum parsimony methods clearly showed
      that the delimitation of these related yeast species is possible by using RAPD
      analysis. Four groups of strains, corresponding to the species S. bayanus, S.
      cerevisiae, S. paradoxus and S. pastorianus, were obtained. Within the S. bayanus
      taxon, two groups of strains were observed. One includes the former type strain
      of S. uvarum, CECT1969(T), and closely related wine strains (S. bayanus var.
      uvarum), whilst the other contains S. bayanus type strain CECT1941(T) and strains
      CECT1991 and 10513 (S. bayanus var. bayanus). The heterogeneous S. paradoxus
      group was divided into three lineages, corresponding to different geographic
      origin, American, Japanese and European populations. In addition, due to the
      multilocus nature of the RAPD-PCR marker, this method is both useful and
      appropriate for the identification of the hybrid origin of S. pastorianus. The
      hybrid nature was deduced from the analysis of the fraction of bands shared by
      each hybrid strain and the parental species. Among the 58 strains analysed, six
      S. pastorianus strains were hybrids, although the fraction of genome coming from
      each parent varied depending on the strain.

PMID- 14587105
TI  - Current role of the minimally invasive direct aortic surgery for 3-A repair
      (MIDAS-3A).
AB  - Open aneurysmectomy and aortic graft is still associated with a relatively high
      morbidity and mortality. To decrease this surgical stress, less invasive
      procedure, MIDAS-3A technique (Minimally Invasive Direct Aortic Surgery for AAA)
      was developed, utilizing a 5 cm abdominal incision and a video-laparoscopic
      assistance (gas-less) to reach the AAA retroperitoneally. From Nov. 1999 to Dec.
      2002, 80 patients underwent surgery. This technique provides all the benefits of
      an open surgical approach, to be combined with the advantages derived from
      minimized tissue trauma. A comparison between MIDAS-3A and CL (Conventional
      Laparotomy) was performed, monitorizing-nasogastric drainage;--initial feeding;-
      pulmonary functions (Vital Capacity, and Forced Expiration Volume);--Intensive
      Care Unit recovery (long stay);--length of hospital stay;--operative time;--blood
      loss. The perioperative (30 days) mortality (2.5%), and the morbidity (7.5%) was
      equal in both groups. No conversion to conventional laparotomy occurred. MIDAS-3A
      has significantly reduced length of hospital stay (3.5 days), and pulmonary
      dysfunctions. This technique provides all the benefits of open surgical approach,
      to be combined with the advantages derived from minimized tissue trauma. MIDAS-3A
      reduced trauma and pain, which resulted in a shorter hospital stay, and so lower
      expense and better financial consequences.

PMID- 14587106
TI  - [Intraoperative recovery of blood in surgery of infrarenal abdominal aortic
      aneurysm].
AB  - The aim of the study was to evaluate the possibility of reducing the blood loss
      during elective surgery for abdominal aortic aneurysms using particular
      intraoperative surgical expedients. From 1993 to 1999, 200 patients were
      recruited into the study. We performed 90 aorto-aortic, 84 aorto-bisiliac, 4
      aorto-iliac-femoral, 12 aorto-bisiliac-hypogastric, and 10 aorto-bifemoral
      reconstructions. Several surgical techniques were used and are described in
      detail. The mortality rate was 3.5%. Haemoglobinaemia 24 hours after the
      operation had decreased by 2.5 +/- 0.9 g/dl. In 67% of cases the estimated blood
      loss was lower than 300 ml. There were no transfusions in 44% of cases, and
      autologous transfusions in 17%. The average estimated blood loss was 350 ml, with
      mean reinfusion of 0.98 blood units. Our study suggests the possibility (44%) of
      avoiding the use of blood transfusions thanks to intraoperative blood saving by
      means of particular surgical techniques.

PMID- 14587107
TI  - [Abdominal artery aneurysm and associated surgical abdominal diseases: towards
      optimal timing].
AB  - The purpose of this study was to assess which modalities offered the best timing
      in the treatment of abdominal aortic aneurysms associated with other abdominal
      surgical diseases. From January 1984 to December 2002, 372 patients underwent
      surgery for abdominal aortic aneurysms, 350 men (94%) and 22 women (6%), mean age
      72 years. Of these 10% were operated on urgently. The traditional open technique
      was used in 307 patients, and the endovascular method in the remaining 65 cases.
      In 40 patients (11%) we observed other associated abdominal diseases which were
      treated during the same operation in 34 cases (85%). We had three deaths in the
      34 cases treated in the same operation (9%). In the remaining cases no
      perioperative mortality was registered. There were no cases of prosthesis
      infection. The mean hospital stay was 9 days. Simultaneous treatment appears, on
      the one hand, to carry an increased operative risk and increased mortality and,
      on the other, to present the advantage of having to perform only one surgical
      procedure. The advent of the endovascular method allows us to postpone the
      treatment of the associated disease without increasing the technical difficulty
      of the second operation.

PMID- 14587108
TI  - [Antibiotic prophylaxis in laparoscopic cholecystectomy: from empiricism to
      evidence. Review of the problem and proposal of a randomized trial of the Lap
      Group Roma].
AB  - More than 10 years after its appearance in clinical practice, laparoscopic
      cholecystectomy can now be considered the standard operation for gallstone
      disease. However, some aspects of this operation are still debated. The need to
      perform routine antibiotic prophylaxis in order to reduce the incidence of
      infectious complications is still a matter of controversy. International
      guidelines do not recommend its routine use. The evidence for this, however, is
      rather limited, because there are no randomized trials with a sufficient number
      of cases to avoid a type II error. The authors, on behalf of the Lap Group Roma,
      introduce the protocol of a multicenter prospective randomized controlled
      clinical trial designed to find a definitive answer to this problem.

PMID- 14587109
TI  - The diagnosis of non-palpable lesions in laparoscopic surgery of the colon.
AB  - The identification of small neoplasms or areas presenting lesions associated with
      previous endoscopic polypectomy is one of the major problems in laparoscopic
      colonic resection. The aim of our study was to evaluate the effectiveness of
      tattooing with Indian ink to identify the area of the colon that is the site of
      the lesion in order to be able to perform colonic resections with oncologically
      correct margins. Eighty-four patients were observed with polypoid lesions or
      diagnosed as presenting lesions associated with endoscopic polypectomy for which
      colonic resection had been recommended. Marking was performed during preoperative
      colonoscopy by injecting 1 ml of Indian ink solution with a sclerotherapy needle
      into each of the four quadrants of the colon wall. This method, which is simple
      to execute, invariably allowed easy identification of the site of the neoplasm
      and laparoscopic colon resection with correct oncological margins. In the 84
      cases, we recorded only one complication (1.1%) due to a paucisymptomatic
      microperforation discovered during the operation. The identification of small
      colon lesions can be performed easily using Indian ink. It is a simple, quick
      method which, if performed properly, always allows the site of the lesion to be
      identified and is associated with a negligible rate of complications.

PMID- 14587110
TI  - Control results on a sample of patients subjected to total thyroidectomy for
      papillary carcinoma: proposal for a personal diagnostic-therapeutic follow-up.
AB  - Well-differentiated thyroid neoplasms may be included among the most frequently
      occurring thyroid carcinomas. Papillary ca. is without doubt the best behaved
      type. The aim of the present work is to perform a retrospective case history
      study to assess patients with con papillary ca. who have been treated surgically
      over the last 17 years and have been subjected to periodic checks. A sample of
      patients was therefore extrapolated who had all undergone total thyroidectomy for
      papillary ca. of the thyroid. The incidence of local recurrence of the disease
      was verified, together with the results at distance. Furthermore, the assessments
      performed were evaluated and compared. From the sample of patients observed we
      inferred that papillary carcinoma of the thyroid can have a good prognosis over
      time provided periodic random checks are carried out.

PMID- 14587111
TI  - [Sentinel lymph node in breast cancer: experience of 4 years].
AB  - The aim of the study was to describe our experience with sentinel lymph node
      biopsy in patients with breast cancer. 326 consecutive patients with breast
      cancer operated on from December 1998 to December 2002 were studied. All patients
      gave their informed consent. Patients were mapped with an intradermal injection
      of Tc-99 (median dose: 0.5 mCi) and/or Patent Blue. Sentinel lymph nodes were
      analyzed with serial sections. 333 procedures were performed in the 326 patients.
      A median of two sentinel lymph nodes were identified in 322 cases (97%). 3165
      additional non-sentinel lymph nodes were removed and analyzed to assess the
      accuracy of the technique. The correlation between sentinel lymph nodes and final
      pathological status was 97% (314/322). In 66/133 cases with axillary metastases
      (50%) the sentinel lymph node was the only site of metastasis. Micrometastases
      were diagnosed in 35/66 cases (26%), while isolated tumour cells were found in 15
      cases (11%). At a median follow-up of 21 months one patient presented an axillary
      relapse (0.3%). Our experience confirms that sentinel lymph node biopsy is
      accurate and reproducible. Routine axillary dissection is no longer the gold
      standard in patients with early breast cancer. Prospective studies are under way
      in an attempt to provide, definitive answers.

PMID- 14587112
TI  - [Cystic type adrenal mass. Clinical-radiologic contribution to 7 cases treated
      with surgery].
AB  - The aim of the study was to evaluate the accuracy of our imaging protocol with
      regard to adrenal masses of cystic nature. Seventy-four adrenal lesions were
      surgically removed over the period 1998-2002. Of these 7 were diagnosed as cysts
      or pseudocysts. All the patients were studied by abdominal US, CT and/or MRI. In
      2 cases, an adrenal primary malignancy was suspected. The lesions of 2 more
      patients, radiologically identified as cysts, were interpreted as hepatic
      echinococcus cyst and mesenteric cyst, respectively; these patients underwent
      open surgery. In 3 cases an adrenal cystic tumour was correctly diagnosed and a
      laparoscopic adrenalectomy performed. The histopathological examination of the
      surgical specimens showed that the preoperative diagnosis failed to ascertain the
      true nature of the lesion in 4/7 cases (57%). The 2 suspected adrenal carcinomas
      turned out to be an epithelial cyst and a pseudocyst, respectively; the suspected
      hepatic echinococcus cyst and the mesenterial cyst were adrenal pseudocysts. Two
      of the 3 remaining cases were endothelial cysts and the third a pseudocysts. In
      the presence of adrenal masses of cystic nature, the preoperative diagnosis may
      easily be inaccurate and adversely influence the surgical approach, especially if
      a misdiagnosis of primary adrenal malignancy is made.

PMID- 14587113
TI  - [Surgical treatment of rectal prolapse with transanal resection according to
      Altemeier. Experience and results].
AB  - In recent years the number of patients with partial or total rectal prolapse has
      increased. Numerous techniques and surgical approaches have been described for
      its treatment. In this study we examine the main ones and stress the advantages
      of the transanal-perineal resection technique according to Altemeier and modified
      by Prasad, which we have used to treat the condition in the last 15 years. From
      1988 to 2002, 269 patients with "haemorrhoidal prolapse" were referred to our
      department; 146 were females (54%), and the mean age was 58 years. Clinical
      examination and proctosigmoidoscopy revealed the presence of total rectal
      prolapse in 41 patients (15%, 32 F, 9 M), complicated in 4 cases by moderate
      incontinence and associated in 3 cases with post-haemorrhoidectomy stenosis.
      These 41 patients underwent transanal resection according to Altemeier. Thirty
      four of them (83%) were operated on under local anaesthesia with sedation, 5
      patients (12%) under peridural anaesthesia and 2 patients (5%) under narcosis.
      The mean hospital stay was 5 days and depended on the time of the first
      spontaneous evacuation. Check-ups were performed after 7 days, 1 months and every
      3 months for 1 year. There was no postoperative mortality, and only 1 case of
      postoperative haemorrhage, which did not require reoperation, in a patient with a
      previous myocardial infarct who spontaneously continued to take salicylates up to
      24 h before surgery. Thirty-three patients (80%) had their first postoperative
      evacuation within 48 h of surgery after taking sorbitol orally in the evening, 6
      patients (15%) within 72 h, and 2 patients (5%) on postoperative day 4. No
      evacuative enemas were performed. We observed clinical healing in all patients 1
      month after the operation, and regular, spontaneous evacuations without the use
      of oral laxatives. Stool or gas incontinence were never observed or reported.
      During the follow-up, only in 2% of cases did we observe partial recurrence of
      the prolapse. The choice between the numerous surgical techniques for correcting
      rectal prolapse, depends on the state of the disease, on the patient's general
      condition and on the surgeon's experience with the various techniques. The
      perineal approach proposed by Altemeier and modified by Prasad presents a low
      risk of mortality and immediate complications, as confirmed by our experience,
      even in high risk patients, and relatively easy execution. It would appear,
      moreover, to be the only technique capable of correcting the preoperative
      incontinence sometimes present.

PMID- 14587114
TI  - [Alternative surgical approaches to bilio-digestive diversions in iatrogenic
      lesions of the bile ducts].
AB  - The aim of this report was to evaluate the indications and limitations of non
      anastomotic surgical repair in patients with bile duct injuries. These surgical
      approaches include both major and minor surgical procedures. The authors describe
      each procedure and conclude that: (i) specific diagnostic procedures are
      necessary to identify the exact level and severity of the injury; (ii) repair of
      bile duct injuries requires different approaches, which is only possible in
      specialized departments; and (iii) non-anastomotic surgical repair of bile duct
      injuries should be limited to cases detected during operation or in the immediate
      postoperative period.

PMID- 14587115
TI  - [Minilaparoscopic appendectomy: which indications?].
AB  - Laparoscopy has gained widespread acceptance in common surgical practice as a
      diagnostic and therapeutic tool. Suspected appendicitis is still a diagnostic
      challenge to the general surgeon. A correct diagnosis is crucial because of the
      various diseases that may be responsible for the same symptoms, in order to plan
      the appropriate procedure or avoid an unnecessary laparotomy. Laparoscopy is the
      only minimally invasive technique to allow at the same time for adequate
      diagnosis, appropriate treatment and the best abdominal approach. Minilaparoscopy
      would appear to be a natural further step in the development of this technique.
      The aim of the present work was to illustrate retrospectively the results of an
      initial case-control study of minilaparoscopy vs. laparoscopy carried out at our
      institution. Between January and December 2002 a total of 86 patients underwent
      emergency and/or urgent appendectomy. Among them, 68 (79%) were operated on
      laparoscopically (37 [54.4%] with a minilaparoscopic approach and 31 with
      conventional laparoscopy), while 18 (21%) were treated by laparotomy, as
      performed by a well-trained surgical team. In the minilaparoscop group we
      registered no conversions to laparotomy and only one major postoperative
      complication (intra-abdominal abscess treated laparoscopically). As regards the
      postoperative period, generally speaking, the patients' conditions (analgesic
      treatment, flatus, diet, hospital discharge) were broadly the same as in the
      laparoscopic group. Though limited by its initial retrospective character, the
      present study shows that minilaparoscopic appendectomy is as safe and effective
      as classical laparoscopic surgery, and seems to be associated with less trauma
      and a more rapid postoperative recovery. Such features make minilaparoscopy a
      challenging alternative to conventional laparoscopy (and, of course, laparotomy)
      in patients referred for urgent abdominal and/or pelvic surgery.

PMID- 14587117
TI  - [Non-functioning neuroendocrine tumor of the pancreas: report of a clinical case
      and review of the literature].
AB  - The authors report the case of a 26-year-old woman, with a palpable abdominal
      mass, dyspepsia, pain and weight loss. These symptoms were caused by a non
      functioning or biologically inactive neuroendocrine tumour (BINT), weighing 510 g
      and located in the tail of the pancreas. The treatment opted for was a surgical
      resection consisting in a distal pancreatectomy. The results of the operation
      were satisfactory and the woman is now alive and in good health, without
      recurrence, after 7 years. The authors then go on to analyse the concept of non
      functioning neuroendocrine tumours and the problems relating to their symptoms,
      location and nature. These tumours, which arise, from the pancreatic islet cells,
      fail to produce a clinical syndrome owing to insufficient peptide production or
      insufficient release, or concurrent secretion, of inhibitory peptides by the
      tumour or production of biologically inactive molecular forms of the peptides
      (without clinical effects). The value of tumour markers and the indications and
      type of surgery are also discussed according to the different patterns of tumour
      spread (local, locoregional and metastatic disease). It is stressed that a
      complete surgical resection is the only curative treatment for these tumours.
      Encouraging results have been recently obtained by adjuvant treatment with
      somatostatin analogues, chemotherapeutic agents and/or inteferon.

PMID- 14587116
TI  - [Biologic tolerance of prolene prosthesis in inguinal hernia repair].
AB  - The aim of this study was to evaluate the efficacy, safety and durability of a
      calibrated inguinal hernioplasty polypropylene prosthesis, particularly in
      relation to the microbiological phenomena that may set in the vicinity of the
      polypropylene plugs and mesh employed. Over the period from January 1994 to
      December 2002, 1416 operations were carried out for inguinal hernia. In 5 of
      these patients we conducted an immunological study to assess serum cytokine
      concentrations. In addition, we incubated peripheral blood mononuclear cells for
      24 or 72 hours in RPMI 1640 medium added with 10% FCS, with or without 0.5 cm2 of
      polypropylene. We then evaluated cytokine levels in the supernatant of these
      cultures. It proved impossible, either in vivo or in vitro, to detect appreciable
      levels of IL-10 or IP-10. Serum levels of IFN-gamma, TNF-alpha, IL-18 and IL-6
      increased in the postoperative phases as compared to the preoperative period. In
      the study performed in vitro, in the presence of prosthetic material there was a
      remarkable increase in the production of TNF-alpha and INF-gamma both in basal
      conditions and after an appropriate mitogenic stimulus. The results of this study
      allow us to speculate that the use of polypropylene induces remarkable
      chemotactic activity in the tissues adjacent to the prosthesis. The in-vitro
      study data suggest that the presence of polypropylene may stimulate the
      immunocompetent cells of patients with prosthetic implants.

PMID- 14587119
TI  - [Report of a case of Gardner's syndrome: clinical and epidemiologic
      considerations and review of the literature].
AB  - Familial adenomatous polyposis is a hereditary clinical syndrome characterised by
      the presence of numerous adenomatous polyps of the colon and rectum and by
      lesions in other organs. The disease affects various different tissues and
      characteristically presents a variable biological and clinical behaviour. Colon
      polyps are precancerous lesions and the certainty of their malignant evolution
      within the 3rd-4th decades of life is now practically an established, extensively
      documented fact. Recently, new methods of genetic screening, prevention and early
      diagnosis and, as a result, more advanced treatment protocols have been
      introduced in clinical practice, thus offering young patients diagnosed as
      suffering from familial adenomatous polyposis better prospects and a better
      quality of life. The patient in our case came in for medical observation for
      abdominal pain experienced close to the scar of a previous appendectomy and for
      the presence of an abdominal tumefaction on the same side. Initially the patient
      underwent surgical resection of the growth that proved to be a desmoid tumour of
      the abdominal wall. The results of the pathology examination and the patients'
      long-term disease and family history led to a presumptive diagnosis of familial
      adenomatous polyposis, which was then confirmed by the appropriate instrumental
      examinations. Genetic tests on the patient's relatives yielded the same diagnosis
      in some of them. On the basis of our personal experience and a thorough review of
      the literature we can safely state that no medical treatment currently available
      is capable of reducing, let alone definitively eliminating colon polyps. To date,
      then, the therapeutic options most commonly adopted are colectomy with ileo
      rectal anastomosis and total conservative proctocolectomy with an ano-ileal pouch
      anastomosis. These two types of surgical procedures yield different results in
      terms of functional capability and oncological radicality with their respective
      repercussions on the patient's quality of life. The choice of the most
      appropriate surgical procedure is made on the basis of a series of parameters
      such as age, site of the polyps, number of polyps, degree of cell atypia of the
      polyps, and patient willingness to undergo regular check-ups. The current
      tendency advocated by the various authors is to perform a total colectomy as soon
      as possible.

PMID- 14587118
TI  - [Massive hematemesis resulting from stomach rupture caused by pseudoaneurysm of
      the splenic artery in a patient with chronic pancreatitis. A case report].
AB  - The authors report a case of a pancreatic pseudocyst, due to alcoholic chronic
      pancreatitis, that was transformed into a pseudoaneurysm of the splenic artery as
      a result of vascular erosion and that manifested itself with massive haematemesis
      due to spontaneous fistulisation in the stomach. After defining the incidence of
      the pancreatic disease and of this unusual form of gastric bleeding, particular
      attention is devoted to the clinical data and to the aetiopathogenic and
      physiopathological mechanisms involved in the vascular glandular and
      periglandular damage, outlining the sources and sites of bleeding. The authors go
      on to discuss the rationale in using imaging techniques, which cannot ignore the
      haemodynamic conditions of the patient and the conviction that the execution time
      of a selective coeliac arteriography never represents an unacceptable delay in
      the management of a life-threatening ruptured pancreatic pseudoaneurysm. This
      conviction is due both to the therapeutic potential inherent in the method itself
      and to the greater safety with which the following operation can be performed,
      owing to the topographical guidance the procedure provides. After a review of the
      conditions that make the treatment difficult, the authors stress the importance
      of a certain measure of eclecticism and careful planning to obtain effective and
      safe results. Only the combined, integrated efforts of the interventional
      radiologist and the surgeon can ensure rapid stabilisation of the bleeding and
      the desired improvement in survival.

PMID- 14587121
TI  - [Benign cystic mesothelioma with multiple recurrences: a clinical case].
AB  - Benign multicystic mesothelioma is a rare disease with a high tendency to local
      recurrence, but with no tendency to malignancy. The correct diagnosis can be made
      by histopathological examination in conjunction with immunohistochemical and
      ultrastructural evaluations. A case of benign cystic mesothelioma recurring three
      times in a 48-year-old woman is reported, and the management of this disease and
      the importance of radical surgery are discussed.

PMID- 14587120
TI  - Renal allograft rupture caused by acute tubular necrosis.
AB  - Renal allograft rupture is a rare but potentially lethal complication of kidney
      transplantation. A renal allograft recipient receiving quadruple
      immunosuppressive therapy developed a spontaneous allograft rupture 13 days after
      kidney transplantation. Warm ischaemia time during the transplant was 80 minutes.
      The ruptured kidney graft could not be salvaged because of the patient's
      haemodynamic instability. The histopathological examination showed interstitial
      oedema with severe acute tubular necrosis with no signs of acute rejection. The
      most common causes of renal graft rupture are acute rejection and vein
      thrombosis, while acute tubular necrosis may only rarely be responsible for this
      complication. Renal graft rupture may be the result of interstitial damage
      attributed both to the prolonged warm ischaemia time during the transplant and to
      post-transplant acute tubular necrosis in the absence of graft rejection. In
      those patients whose haemodynamic status cannot be stabilized by appropriate
      aggressive haemodynamic support therapy, graft nephrectomy should be considered
      the only definitive treatment.

PMID- 14587122
TI  - [Subtotal splenectomy for large splenic cyst].
AB  - Fulminant sepsis described in childhood has long stimulated surgeons to attempt
      partial or total preservation of the spleen when possible. Persistence of splenic
      tissue ensures preservation of the immunological competence of the organ. Total
      splenectomy ought to be avoided in the first 10 years of life; in subsequent
      years an attempt to partially preserve the organ is to be recommended. A
      segmental arterial vascularization with avascular interlobar planes has been
      demonstrated in the spleen allowing partial resection of the organ. We report a
      case of a voluminous epithelial splenic cyst in a teenager removed by subtotal
      splenectomy.

PMID- 14587123
TI  - Promoting healthy and successful aging in everyday clinical practice.

PMID- 14587124
TI  - Exercise in older adults.
AB  - Physical activity and exercise are beneficial to overall health and delay
      disability, even in the oldest old. We present data on exercise in older adults
      and its various benefits. Furthermore, we describe exercise programs suitable for
      adults over 65 and identify resources available to both patient and physician.

PMID- 14587125
TI  - Complementary and alternative medicine for the management of osteoarthritis in
      older adults.

PMID- 14587126
TI  - Overcoming the challenges of immunosenescence in the prevention of acute
      respiratory illness in older people.
AB  - This article describes the impact of acute respiratory illness (ARI) and the
      challenges to primary prevention of viral ARI and related morbidity in the age 65
      and older population. Immunosenescence, the immune system's "memory loss" with
      aging, compromises both host defense mechanisms against ARI and effective
      responses to vaccination. Atypical presentations of illness common in older
      people often lead to delayed or missed diagnoses of ARI and disabling
      consequences. Thus, preventing ARI will be more effective than treatment. Even
      with the limited efficacy of current influenza vaccines in older people,
      vaccination is a cost-saving intervention especially in high-risk groups
      including those with chronic heart or lung diseases. Significant opportunities to
      further reduce the morbidity of ARI include developing more effective influenza
      vaccines and vaccines against other ARI. Combining vaccination with antiviral or
      immunoenhancing agents particularly in high-risk groups could optimize the cost
      benefit of additional preventive strategies.

PMID- 14587127
TI  - Neurologic assessment and therapy of patients with impaired mobility.
AB  - Disorders of mobility are an important determinant of function in older persons.
      As a risk factor for falls, these disorders also contribute to significant
      morbidity and mortality in older individuals. Although many causes are
      neurologic, potentially reversible nonneurologic contributors need to be
      carefully ruled out. Patients with more advanced mobility impairments may benefit
      from having their specific problem areas defined, with physical therapists then
      providing training programs in specific functional domains.

PMID- 14587128
TI  - Osteoporosis in older men and women.
AB  - Hip fracture incidence accelerates approximately 10 years following the menopause
      in women and after age 70 in men. Approximately one million Americans suffer
      fragility fractures each year at a cost of over 14 billion dollars. The
      disability, mortality and cost of hip and vertebral fractures are substantial in
      the rapidly growing aging population so that prevention of osteoporosis is a
      major public health concern. Bone mineral density (BMD) measurement is used to
      make the diagnosis of osteoporosis prior to incident fracture, and to predict
      fracture risk. Recommendations for treatment and prevention of osteoporosis based
      on bone mineral density score published by the World Health Organization and the
      National Osteoporosis Foundation are outlined.

PMID- 14587129
TI  - Lower urinary tract symptoms in the older male.
AB  - Lower urinary tract symptoms (LUTS) are common in older men and include urinary
      frequency, urgency, nocturia and slow stream. Traditionally, this symptom complex
      has been called benign prostatic hypertrophy or prostatism, yet such symptoms may
      also result from detrusor over-activity and/or excessive urine output. Clinical
      assessment of older men with LUTS is based on a careful history, a clinical
      examination and a check of the postvoid residual, with urodynamic studies
      reserved for select individuals. Factors such as mobility, constipation and fluid
      balance must also be considered. These combined with a variety of pharmacologic
      agents (antispasmodics, alpha-antagonists, 5 alpha reductase inhibitors) offer
      great potential for improving the quality of life of individuals with LUTS.

PMID- 14587130
TI  - Evaluation and management of urinary incontinence in elderly women.
AB  - Urinary incontinence is a common problem among older women, with a great impact
      on their quality of life, self-esteem and ability to live independently. Although
      often neglected by both patients and health-care providers, a variety of
      behavioral, pharmacologic and surgical interventions are now available to resolve
      or improve the symptoms of most older women who are incontinent. Since many of
      the factors which contribute to continence in late life lie outside of the
      bladder, the assessment of urinary incontinence in older women must extend beyond
      the genitourinary tract, assessing domains such as mobility, fluid balance and
      cognition. The primary care physician in uniquely placed in being able to
      diagnose this problem, to initiate treatment in many patients and to refer those
      requiring additional specialized expertise.

PMID- 14587131
TI  - Congestive heart failure and the elderly.
AB  - As patients age, congestive heart failure becomes an increasingly important
      problem and accounts for up to 20% of hospital admissions for patients over 65
      years. With technological improvements in the treatment of coronary artery
      disease, improved survival after myocardial infarction, and better hypertension
      therapy, patients are living longer, thus the need for successful management of
      older patients with chronic heart failure. The elderly, especially minorities,
      tend to be under-represented in congestive heart failure trials. This article
      will focus on the care of the geriatric patient with congestive heart failure.

PMID- 14587132
TI  - Diagnosis and management of Alzheimer's disease.
AB  - Alzheimer's disease is a progressive neurological condition that usually presents
      with short-term memory impairment, and then progresses to profound cognitive and
      physical disability. The diagnosis is based primarily on clinical findings with a
      definitive diagnosis only being possible with pathological examination of brain
      tissue. Alzheimer's disease causes distress to patients, families and caregivers.
      Most patients with advanced Alzheimer's disease need 24-hour supervision, often
      provided in a long-term care setting. Although no cure is available, with a
      variety of treatments, modest but measurable benefits are available. Research is
      being conducted to find more effective treatments and hopefully in time a cure or
      means of prevention. All physicians whose practice includes older patients need
      to possess some familiarity with the diagnosis and management of Alzheimer's
      disease.

PMID- 14587133
TI  - Improving the care of older adults with developmental disabilities.

PMID- 14587134
TI  - Medicine and the older American.

PMID- 14587135
TI  - Medical errors and adverse events: who's accountable or who should be?

PMID- 14587136
TI  - Mediation to become option to resolve Medicare beneficiary complaints.

PMID- 14587137
TI  - [Surprises during urological interventions due to incomplete medical histories].
AB  - Two men, aged 37 and 47 years old, visited the urologist because of secondary
      infertility. These underwent an examination whilst under general anaesthesia; the
      examination was converted to a vasovasostomy, as in both cases it was found that
      a vasectomy had previously been performed. A third man, 56 years old, wished to
      undergo vasovasostomy; a few months later he appeared to have pre-existent
      retrograde ejaculation after an earlier bladder neck incision. For various
      reasons, no adequate information about the psychosocial and medical history was
      available. These case histories stress the importance of all of the patient
      records being available prior to an intervention.

PMID- 14587138
TI  - [Advantages and disadvantages of a "no-fault" compensation system].
AB  - Should the present legal regulation of medical negligence be replaced by a no
      fault compensation system (NFCS)? The Dutch government is preparing a viewpoint
      on this issue on the basis of a research report that describes the pros and cons
      of a NFCS. Recently, the British chief medical officer (CMO) rejected the
      introduction of a comprehensive NFCS. Instead, the CMO proposed to introduce
      other reforms to mitigate the disadvantages of the present system of medical
      litigation. A NFCS has certain advantages but is supposedly very expensive. Other
      policy measures can be considered as well.

PMID- 14587139
TI  - [Raised creatine-kinase serum activity: not necessarily a sign of disease].
AB  - Hyper-creatine-kinase(CK)-aemia in patients without neurological abnormalities
      may be sign of a subclinical neuromuscular disorder. Initial screening of
      patients with hyper-CK-aemia must include careful history taking and a
      neurological examination. Appropriate blood tests to exclude aeanthocytosis and
      glycogen storage disease type II must be done. The diagnostic value of a skeletal
      muscle biopsy and electromyography is small. A muscle biopsy to exclude
      dystrophinopathy is indicated if the CK activity exceeds 5 times the upper limit
      of the normal range. If the results of initial screening are normal, patients
      with idiopathic hyper-CK-aemia fare quite well at 7-year follow-up. Also,
      standardized exercise tests in these patients have provided no evidence of
      increased muscle vulnerability. Thus, in most of these patients, hyper-CK-aemia
      probably does not reflect disease.

PMID- 14587140
TI  - [Reperfusion therapy for patients with an acute myocardial infarct with ST
      segment elevation: fibrinolysis versus transport to a cardiac center for primary
      angioplasty].
AB  - Although fibrinolytic therapy for acute myocardial infarction is widely used and
      can be administered prior to hospitalisation, it is only successful in restoring
      full early coronary patency in about 60% of patients and has a 0.5% to 1% risk of
      severe side effects. Primary percutaneous coronary angioplasty carried out as an
      alternative to fibrinolysis avoids the risk of fibrinolytic therapy and restores
      patency in nearly 90% of cases. Data from randomised trials of primary
      angioplasty versus fibrinolytic therapy in acute myocardial infarction reveal
      that angioplasty results in a significant reduction in mortality. Furthermore,
      primary angioplasty can be improved by means of a new pre-angioplasty drug
      therapy (so-called facilitated primary angioplasty). Transport to a cardiac
      centre for primary angioplasty (of which there are 14 in the Netherlands) is
      feasible and safe. Although the time to treatment is delayed by a further 90
      minutes, it tends to save lives and prevent strokes and it also significantly
      reduces the incidence of reinfarction. Interestingly, the time gained to
      treatment with prehospital fibrinolytic therapy compared to in-hospital therapy
      gave an outcome similar to that found upon comparing transport and primary
      angioplasty. Rescue procedures (angioplasty) within 24 hours are necessary in
      about 30% of patients who are initially treated with lytic therapy. These results
      support prehospital triage for fibrinolysis or transport to a cardiac centre,
      where early angioplasty can be performed if clinically indicated. A trial to
      determine the policy of choice is at present being conducted in the Netherlands.

PMID- 14587141
TI  - [Depression: longer-lasting episode not an automatic indication for referral].
AB  - During episodes of depression, patients exhibit a low mood and a number of other
      emotional and/or physical symptoms for a certain period of time. Regarding
      depression as just the defined episode when patients meet the criteria for
      diagnosis, ignores the fluctuating character of the illness and the role of the
      patient. The patient is, after all, the one who decides if and when the symptoms
      experienced are important enough to seek medical assistance. How a patient with
      depression should be treated, and whether or not and to whom the patient should
      be referred, depends on more than just the severity of the depression. This is
      because severity involves more than just the number of symptoms when the
      depression was first diagnosed. Ineffective coping behaviour and lack of social
      support both negatively influence the course of depression and if the initial
      treatment is not effective enough, the episode will be prolonged. The interest
      and skills of the general practitioners as well as the expectations and former
      experiences of the patient play a major role in deciding whether to refer a
      patient to secondary care.

PMID- 14587144
TI  - [Health risks raised by ephedra in food supplements].
AB  - In recent years, the use of herbal preparations containing Ephedra has increased
      and so has the number of reported negative health effects. Ephedra products are
      used as a slimming aid, (sports) performance enhancer, stimulant during long
      working hours and as a plant-based ecstasy-surrogate in the party scene. The
      health effects caused by the use of Ephedra products are mainly restlessness,
      agitation, tachycardia and palpitations. The most important risk factors are the
      relatively high amounts of Ephedra alkaloids in the preparations available, the
      varying concentrations within different batches of the same product, the
      relatively high risk of voluntary overdosing in order to improve results and the
      occurrence of interactions with the concurrent use of other stimulants and
      medicines.

PMID- 14587143
TI  - [The guideline 'Detection of visual disorders at the age of 0-19' from the Dutch
      Association of Child Health Care].
AB  - The child health-care guideline 'Detection of visual disorders at the age of 0
      19' draws attention to the importance of early detection of visual disorders and
      provides guidelines to child health-care workers for detecting disorders during
      routine check-ups. Children under the age of 3 are examined by the 'Early
      detection of visual disorders' method. Picture charts may be used for children
      from the age 3 onwards. From the age of 3.5 charts which follow the Snellen
      principle such as the Landolt-C chart should be used. Screening for refraction
      after the age of 7 and screening for colour blindness are not necessary. Children
      born before 32 weeks of pregnancy, children with a family history of visual
      disorders and mentally disabled children have an increased risk of visual
      disorders.

PMID- 14587142
TI  - [Nutrition and health--unclear association between intake of vitamin E and the
      risk of coronary heart disease].
AB  - Vitamin E is a fat-soluble antioxidant and is possibly involved in the prevention
      of coronary heart disease by inhibiting oxidative modification of LDL
      cholesterol. The results of studies on the association between vitamin-E intake
      and coronary heart disease are inconsistent in observational studies and absent
      in large-scale intervention studies. This may be the consequence of confounding
      in observational studies and imperfections in the design of intervention trials.
      Another explanation is that vitamin E may only function protectively in the
      presence of sufficient co-antioxidants. At present, there is no evidence that
      vitamin E lowers the risk of coronary heart disease.

PMID- 14587145
TI  - [Diagnostic image (160). A woman with a tapeworm in a stoma. Taenia saginata].
AB  - A 39-year-old woman had a proctocolectomy, an ileo-pouch-anal anastomosis and a
      temporary intestinal stoma. The stoma discharged a tapeworm, Taenia saginata.

PMID- 14587146
TI  - [Continuous subcutaneous insulin infusion in diabetes mellitus type 1 and 2:
      lower HbA1c-values and a high level of patient satisfaction].
AB  - OBJECTIVE: To determine the HbA1c-values and the degree of satisfaction of
      patients who had switched from multiple subcutaneous insulin injections to
      continuous subcutaneous insulin infusion (CSII). DESIGN: Retrospective. METHOD:
      Data were collected and evaluated from all patients with type 1 or 2 diabetes
      mellitus who started treatment with CSII in the period from 1 January 1999 to 31
      December 2001 in the Rijnmond-Zuid Medical Centre, Zuider site, Rotterdam, the
      Netherlands. The data included the insulin dosage and HbA1c-percentages before
      and three months after the start of CSII, and the degree of satisfaction of the
      patients on a scale from 1 (poor) to 10 (good). RESULTS: Of the 57 patients who
      started CSII, two resumed multiple daily subcutaneous injections within a few
      months. Of the other 55 patients, 36 (including 15 men) had type-1 diabetes, with
      an average age of 36.1 years, and 19 (including 8 men) had type-2 diabetes, with
      an average age of 49.7 years. Poor regulation of the blood glucose levels was the
      main reason (n = 40; 73%) for switching to CSII. In the 36 patients with type-1
      diabetes, there was no significant change in the total dose of insulin before and
      during CSII, while the mean HbA1c-level decreased from 8.2 (SD: 1.2) to 7.3% (SD:
      1.0; p = 0.0005). In the 19 patients with type-2 diabetes, there was also no
      significant change in insulin dosage, while the HbA1c-level decreased from 8.1
      (SD: 1.0) to 7.6% (SD: 1.1; p = 0.056). All 47 interviewed patients were
      satisfied with the treatment. The mean score was 8.3 in type-1 diabetes mellitus
      and 8.1 in type-2 diabetes mellitus. CONCLUSION: Following three months on CSII,
      the average HbA1c-percentages were lower than during the previous treatment with
      multiple subcutaneous insulin injections. The patients were satisfied with the
      convenience of the treatment.

PMID- 14587148
TI  - [Nuchal rigidity in children: meningitis or not?].

PMID- 14587147
TI  - [Chickenpox in pregnancy with serious consequences for both mother and child].
AB  - A 41-year-old woman with chickenpox in the third trimester of her pregnancy was
      admitted to the Intensive Care Unit of our hospital for ventilatory support. She
      was treated with aciclovir, amoxicillin-clavulanic acid and erythromycin. Her
      baby was delivered by forceps following placental abruption. After delivery, both
      mother and child recovered slowly but could eventually leave the hospital in good
      condition. If a pregnant woman without a prior history of varicella-zoster
      infection is exposed to a child that has chickenpox, passive immunisation with
      varicella-zoster immunoglobulin should be administered. This reduces the risk of
      maternal complications and may prevent a fetal varicella syndrome. If the mother
      has already developed chickenpox and there are serious complications, she should
      be treated with intravenous aciclovir. If possible, delivery should be delayed
      until 5 days after the onset of maternal chickenpox.

PMID- 14587149
TI  - [Postsurgical pain and weakness in the shoulder-arm region: iatrogenic or not?].

PMID- 14587150
TI  - [Brain abscess: a difficult diagnosis].

PMID- 14587151
TI  - [Diagnostic image (139). An intellectually disabled man with a distended
      abdomen].

PMID- 14587152
TI  - [The European program for prevention of cardiovascular diseases].

PMID- 14587153
TI  - [Neurokinin antagonists as antiemetics].

PMID- 14587154
TI  - [Reflux disease. Current aspects of etiology, diagnosis and treatment].

PMID- 14587155
TI  - [Gallbladder and bile duct diseases].

PMID- 14587156
TI  - [Hemorrhoidal diseases].

PMID- 14587157
TI  - Epicardial electroanatomical mapping for intraoperative evaluation of bilateral
      pulmonary vein isolation.
AB  - Eight patients (pts; 2 female, 58 +/- 12 yrs) with paroxysmal atrial fibrillation
      (AF) (duration 39 +/- 20 months) underwent AF surgery, with concomitant
      myocardial revascularization in 2 pts and myomectomy in 1 (HOCM). AF was
      idiopathic in the remaining 5 pts. AF surgery consisted of bilateral isolation of
      the pulmonary veins (PV) using radiofrequency (RF) energy applied epicardially by
      a heptapolar catheter (Thermaline) in 5 pts and by a new system (Atricure) in 3
      pts. For the former, each set of 7 simultaneous applications aimed at a maximum
      duration of 2 + 2 min., preset temperature 80 degrees C and output 150 watts.
      With the new system, bipolar applications were carried out; energy delivery was
      controlled by impedance monitoring and applications were ended after abrupt,
      sustained elevation of impedance. Epicardial bipolar voltage mapping (CARTO) was
      performed before and after each RF procedure. Using the navigator catheter,
      points were recorded at the insertion of each PV and at the non-isolated left
      atrial posterior wall. The amplitude of the local electrograms (LE) was measured
      before and after RF applications. If the LE amplitude inside the isolated zone
      was not 0.1 mV and not reduced by > 80%, a second application was performed. A
      maximum of 2 epicardial applications were carried out in each pt and if the final
      result was unsatisfactory, further endocardial applications were performed.
      RESULTS: Baseline LE amplitudes were > 1 mV in all cases. Successful isolation of
      right PVs was achieved in 7 pts, after one set of applications in 5 and a second
      set in 2. Left PV isolation required 2 sets of epicardial applications in all
      pts, being successful in only 2; 4 pts (one with associated myomectomy and 3 with
      idiopathic AF) received endocardial applications. Overall, bilateral PV isolation
      was achieved in 5 pts. CONCLUSIONS: CARTO bipolar voltage mapping is a fast,
      simple means for evaluation of epicardial PV isolation.

PMID- 14587158
TI  - Mitral valve regurgitation--quantification by Doppler echo (quantitative versus
      semi-quantitative methods).
AB  - Quantification of mitral regurgitation is still a controversial issue. Because
      quantitative analysis using the volumetric method is time-consuming, semi
      quantitative analysis based on the characteristics of the regurgitant jet in the
      left atrium is the method used in daily clinical practice, despite its recognized
      limitations. In the last ten years various papers have proposed the PISA method
      as an alternative to the volumetric one, as the same quantitative parameters-
      regurgitant volume (RV) and effective regurgitant orifice (ERO)--can be obtained
      with a small number of measurements. The aim of the present study was to
      determine the degree of correlation and agreement between the two quantitative
      methods and to what extent the semi-quantitative analysis parameters correlated
      with the quantitative ones. We also compared the performance of the PISA method
      and semi-quantitative analysis in grading mitral regurgitation severity, using
      the volumetric method as gold standard. The study enrolled 77 patients (pts) aged
      62 +/- 13 years (43 M and 34 F) with at least moderate mitral regurgitation
      determined by standard two-dimensional Doppler echo color flow imaging. The
      etiology of mitral valve regurgitation was: degenerative prolapse--40 pts (52%),
      ischemic--24 (31%), dilated cardiomyopathy--4 (5%), other pathologies-9 (12%). A
      sonographer performed the examinations under the supervision of one of two senior
      cardiologists. All quantitative Doppler measurements and calculations were
      performed on-line and the examinations recorded on videotape. Good correlations
      were found between RV (r = 0.81, p < 0.001, SE +/- 25) and ERO (r = 0.85, p <
      0.001, SE +/- 17) measurements obtained by the two quantitative methods. However,
      the agreement was weakened by significant individual differences, particularly in
      the patients with degenerative prolapse. A satisfactory correlation was found
      between the jet area (JA) evaluated by semi-quantitative analysis and the RV and
      ERO calculated by both quantitative methods, with JA showing a tendency to
      underestimate the degree of mitral regurgitation in eccentric jets and to
      overestimate it in jets with central orientation. ROC curve analysis was used to
      evaluate the accuracy of ERO calculated by PISA and the JA by color Doppler in
      identifying different grades of mitral regurgitation defined by the values of ERO
      in the volumetric method. The calculated values of the area under the curve for
      the PISA ERO were higher than those for JA in the identification of patients with
      mild 0.93 (0.84-0.97) vs. 0.80 (0.70-0.89) p = 0.005 as well as severe mitral
      regurgitation 0.95 (0.87-0.98) vs. 0.81 (0.71-0.90) p = 0.006).

PMID- 14587159
TI  - National Donation Network: what reality for heart transplantation?
AB  - The National Organ Donation Network is the structure that provides donation
      logistics for all transplant programmes currently functioning in Portugal
      (including cadaver donation, organs and tissues). In this article the authors
      present the Network, analyze the potential for heart donation, discuss the
      criteria for heart donor assessment and viability and suggest the adoption of
      recipient urgency grading schemes and the implementation of allocation criteria.
      In the coming years a realistic prediction for the maximum capacity of effective
      heart donation of the national network is 70-80 heart transplants per year,
      matching the figure of 7-8 heart transplants per million population and meeting
      70-80% of the estimated needs for heart transplantation at national level. When
      this level is reached, it can be presumed that further improvement will
      necessitate expanding the donor pool, with less restrictive criteria for heart
      donor acceptance.

PMID- 14587160
TI  - Organ donation and heart transplantation: the Portuguese situation.

PMID- 14587161
TI  - Levosimendan: a new approach for the treatment of patients with severe heart
      failure. A brief summary based on a clinical case.
AB  - Looking at the clinical report of a single patients admitted with severely
      decompensated heart failure and successfully managed with levosimendan, the
      authors review the current knowledge about this new drug. The treatment of
      severely decompensated heart failure is currently based on classical
      catecholamines (dopamine and dobutamine). The various new positive inotropics
      investigated in the past have failed to improve survival. In spite of some
      symptomatic improvement an increase in long-term mortality was noticed in
      different trials testing different drugs. More recently a new concept has been
      introduced regarding a new way to improve myocardial contractility and
      vasodilation based on calcium-sensitizing properties with additional action on
      adenosine triphosphate-sensitive potassium channels. Levosimendan is a
      representative of this new class recently launched in the Portuguese market.

PMID- 14587162
TI  - Emerging problems in clinical practice. Ethics and deontology.

PMID- 14587163
TI  - Emerging problems in clinical practice. Resource allocation in cardiology.

PMID- 14587164
TI  - Prevalence of hypercholesterolemia in Portugal and Europe: the same reality?

PMID- 14587165
TI  - Arterial duct occlusion by thrombosis: clinical case.

PMID- 14587166
TI  - Fibrinolytic therapy an ongoing research field.

PMID- 14587168
TI  - Pharmacological reperfusion in acute myocardial infarction after ASSENT 3 and
      GUSTO V.

PMID- 14587167
TI  - Glycoprotein IIb-IIIa inhibitors in unstable coronary syndromes and percutaneous
      interventions--a conservative approach.
AB  - Antagonists of platelet glycoprotein IIb/IIIa have an approved role in preventing
      acute complications and coronary events in the setting of percutaneous coronary
      interventions (PCI). Their use in unstable coronary syndromes out of the PCI
      setting is however debated. This paper summarizes reasons for the ongoing debate
      and highlights areas of uncertainty.

PMID- 14587169
TI  - Long-term subcutaneous and oral anticoagulants after acute coronary syndromes.
AB  - Antithrombotic treatment of acute coronary syndrome consists of aspirin and (low
      molecular weight) heparin, whereas oral glycoprotein IIb/IIIa receptor
      antagonists as a routine cannot be advised and thrombolytic therapy is not
      indicated at all. Long-term protection also consists of antiplatelet therapy and,
      if indicated, by anticoagulant therapy, given either as low-molecular weight
      heparin or as oral anticoagulants.

PMID- 14587170
TI  - Bivalency is costly: bivalent stimuli elicit cautious responding.
AB  - When performing tasks in alternation, substantial slowing occurs when the stimuli
      have features relevant to both tasks (i.e., when stimuli are bivalent as opposed
      to univalent). One possible source of this slowing, herein called a bivalency
      cost, is that encountering bivalent stimuli leads to a more cautious response
      style. To investigate this, we employed a paradigm that required performing three
      simple tasks, with bivalent stimuli occasionally encountered on one task. The
      results show that regardless of the feature overlap among the stimuli used for
      the different tasks, the introduction of bivalent stimuli slowed responding on
      all tasks and it was accompanied by a decrease in response errors. Overall, it
      appears that bivalent stimuli recruit a more cautious approach to task-switching
      performance.

PMID- 14587171
TI  - I like her, because I like myself: self-evaluation as a source of interpersonal
      attitudes.
AB  - Two experiments tested the hypothesis that self-evaluation can serve as a source
      of interpersonal attitudes. In the first study, self-evaluation was manipulated
      by means of false feedback. A subsequent learning phase demonstrated that the co
      occurrence of the self with another individual influenced the evaluation of this
      previously neutral target. Whereas evaluative self-target similarity increased
      under conditions of negative self-evaluation, an opposite effect emerged in the
      positive self-evaluation group. A second study replicated these findings and
      showed that the difference between positive and negative self-evaluation
      conditions disappeared when a load manipulation was applied. The implications of
      self-evaluation for attitude formation processes are discussed.

PMID- 14587172
TI  - The recall of stereotypes: the effects of incidentally activated directed
      forgetting instructions.
AB  - Based on the automotive model (J. A. Bargh, 1990) and the directed forgetting
      paradigm, the present study investigated whether incidentally activated forget
      and remember cues can lead to similar effects as explicitly given instructions.
      To this end, the present paper attempted to replicate the findings of Macrae,
      Bodenhausen, Milne, and Ford (1997) employing their category primes (child
      abuser, neutral), study lists (List 1, List 2), and procedure. Using explicit
      directed forgetting instructions, Experiment 1 showed that the recall of the
      stereotypically relevant words (List 1) was higher when participants were given a
      remember than a forget instruction. This effect was found regardless of the prime
      conditions. Similarly, Experiment 2 showed that participants in the child abuser
      and neutral prime conditions recalled more stereotypically relevant words (List
      1) when they were implicitly cued to remember than to forget these words.
      Experiment 3 showed that cognitively busy participants in the child-abuser, but
      not in the neutral prime condition, recalled more to-be-forgotten stereotypical
      words than nonbusy participants. These results are consistent with Macrae et al.
      s findings, and show that the effects of directed forgetting instructions are
      similar regardless of whether they were given explicitly or were activated
      incidentally. Results are discussed in relation to stereotype maintenance.

PMID- 14587173
TI  - Selective attention to elements in working memory.
AB  - Three experiments with an arithmetic working memory task examine the object
      switch effect first reported by Garavan (1998), which was interpreted as evidence
      for a focus of attention within working memory. Experiments 1a and 1b showed
      object switch costs with a task that requires selective access to items in
      working memory, but did not involve counting, and did not require updating of
      working memory contents, thus ruling out two alternative explanations of
      Garavan's results. Experiment 2 showed object switch costs with a task that
      required no selective access to working memory contents, but involved updating,
      thus providing evidence for a second component to the overall object switch
      costs. Further analyses revealed that the object switch cost increased with
      memory set size; that there were (smaller) switch costs when the switch was to an
      item of the same type; that repeating an arithmetic operation does not have the
      same effect as repeating the object it is applied to; and that object switching
      is not mediated by backward inhibition of the previously focused object.

PMID- 14587174
TI  - Anaphor resolution as a function of spatial distance and priming: exploring the
      spatial distance effect in situation models.
AB  - Anaphor resolution has been found to depend on the spatial distance between the
      reader's focus of attention and the location of the anaphor referent in a
      spatially organized situation model (spatial distance effect; Rinck & Bower,
      1995). This effect implies that a) the situation model is spatially organized and
      b) spatial distance has a stronger effect on the resolution of anaphoric
      reference than the text priming the anaphor referent. In three experiments, adult
      participants read 12 short narratives about protagonists moving around a
      building. Mentionning the location of the anaphor referent in text prior to the
      anaphoric sentence facilitated anaphor resolution. Decreased spatial distance
      consistently facilitated anaphor resolution, even when priming the anaphor
      referent affected anaphor resolution more strongly than spatial distance. Results
      are discussed with regard to the interpretation and reliability of the spatial
      distance effect and the interaction of different representational levels in the
      context of multi-level theories of text comprehension.

PMID- 14587175
TI  - Right or wrong, familiar or novel in pictorial list discrimination learning.
AB  - The interaction between nonassociative learning (presentation frequencies) and
      associative learning (reinforcement rates) in stimulus discrimination performance
      was investigated. Subjects were taught to discriminate lists of visual pattern
      pairs. When they chose the stimulus designated as right they were symbolically
      rewarded and when they chose the stimulus designated as wrong they were
      symbolically penalised. Subjects first learned one list and then another list.
      For a "right" group the pairs of the second list consisted of right stimuli from
      the first list and of novel wrong stimuli. For a "wrong" group it was the other
      way round. The right group transferred some discriminatory performance from the
      first to the second list while the control and wrong groups initially only
      performed near chance with the second list. When the first list involved wrong
      stimuli presented twice as frequently as right stimuli, the wrong group exhibited
      a better transfer than the right group. In a final experiment subjects learned
      lists which consisted of frequent right stimuli paired with scarce wrong stimuli
      and frequent wrong stimuli paired with scarce right stimuli. In later test trials
      these stimuli were shown in new combinations and additionally combined with novel
      stimuli. Subjects preferred to choose the most rewarded stimuli and to avoid the
      most penalised stimuli when the test pairs included at least one frequent
      stimulus. With scarce/scarce or scarce/novel stimulus combinations they performed
      less well or even chose randomly. A simple mathematical model that ascribes
      stimulus choices to a Cartesian combination of stimulus frequency and stimulus
      value succeeds in matching all these results with satisfactory precision.

PMID- 14587176
TI  - Effects of attachment styles on the experience of equity in heterosexual couples
      relationships.
AB  - Employing one correlational and two experimental studies, this paper examines the
      influence of attachment styles (secure, anxious, avoidant) on a person's
      experience of equity in intimate relationships. While one experimental study
      employed a priming technique to stimulate the different attachment styles, the
      other involved vignettes describing fictitious characters with typical attachment
      styles. As the specific hypotheses about the single equity components have been
      developed on the basis of the attachment theory, the equity ratio itself and the
      four equity components (own outcome, own input, partner's outcome, partner's
      input) are analyzed as dependent variables. While partners with a secure
      attachment style tend to describe their relationship as equitable (i.e., they
      give and take extensively), partners who feel anxious about their relationship
      generally see themselves as being in an inequitable, disadvantaged position
      (i.e., they receive little from their partner). The hypothesis that avoidant
      partners would feel advantaged as they were less committed was only supported by
      the correlational study. Against expectations, the results of both experiments
      indicate that avoidant partners generally see themselves (or see avoidant
      vignettes) as being treated equitably, but that there is less emotional exchange
      than is the case with secure partners. Avoidant partners give and take less than
      secure ones.

PMID- 14587177
TI  - [Vacation counseling for cardiology patients. Sick heart during travel].

PMID- 14587178
TI  - [Normal findings or disease? Fungi in the bowel].

PMID- 14587179
TI  - [Substitution study. Is it allowed to give placebos to junkies?].

PMID- 14587180
TI  - [Smallpox vaccination. What happened to prevaccination stuff?].

PMID- 14587181
TI  - [In travellers already more frequent than malaria. Dengue fever in advance].

PMID- 14587182
TI  - [When viruses jump over species boundaries. Are dogs and cats to be permitted
      into bed?].

PMID- 14587183
TI  - [Bed-wetters, finicky eaters, stutterers. Great progress has been made in
      research into causes and treatment].

PMID- 14587184
TI  - [Elimination disorders in childhood. How to make children dry and clean].
AB  - Evacuation disorders include a number of disturbances in which genetic and
      environmental factors play a highly differentiated role. Behind enuresis nocturna
      is a genetic CNS development disorder; a differentiation is made between cases
      with and without diurnal bladder dysfunction. In the first line treatment
      involves the use of an alarm device, while desmopressin is a second-choice
      treatment. In children with diurnal enuresis, there is a range of functional
      disorders of continence to be considered including, in particular, idiopathic
      urge incontinence, urinary incontinence when micturition is suppressed, and
      detrussor sphincter dyscoordination. Prominent among the therapeutic options are
      cognitive-behavioral measures and biofeedback training. Encopresis may develop on
      the soil of acute constipation or underlying psychological factors. Treatment is
      symptom-oriented and also comprised behaviorial measures (toilet training),
      possibly dietary measures and, in the event of constipation, enemas or oral
      laxatives.

PMID- 14587185
TI  - [Eating disorders in children and adolescents].
AB  - Eating disorders in early childhood increase the risk of anorexia or bulimia
      nervosa in adolescents. In the case of babies feeding disorders and pica are
      differentiated. Eating disorders in pre-school and primary school age are common.
      A main cause is neophobia, which can be treated by the observance of certain
      rules at meal-times (taken together with the family). Anorexia and bulimia affect
      mainly adolescents. Anorexia is associated with a number of mental and somatic
      comorbidities that need to be considered for the diagnosis and treatment.

PMID- 14587186
TI  - [Speech and language development disorders in children].
AB  - Despite their frequency and clinical relevance, disturbances in the acquirement
      of language skills are not infrequently overlooked or are recognized too late, in
      particular when the problem is speech understanding, or when behavioral
      disturbances predominate. Diagnostic guidelines differentiate between
      circumscribed articulation disorders and expressive and receptive speech
      problems. The diagnostic work-up must take account of the changes in symptoms
      occurring during the course of the child's development. Mental comorbidity may be
      observed in every second speech-disordered child. For the operationalized
      establishment of speech performance--also during the course of treatment--greater
      use should be made of standardized test procedures. In order to early recognize
      speech acquisition disorders, the regular use of pediatric routine diagnostic
      should be practiced. With regard to management, direct treatment of the child-
      especially when very young--should taken second place to training of the parents
      on language-furthering behavior.

PMID- 14587187
TI  - [Hypertension and the metabolic syndrome. Even children and adolescents require
      treatment].

PMID- 14587188
TI  - [What effect does losing weight have on hypertension?].

PMID- 14587189
TI  - [Current concepts in chronic lymphocytic leukemia. Better chances for young
      patients].

PMID- 14587190
TI  - [Pain therapy with semisynthetic opioids. Patients have opioid-type side effects
      more rarely].

PMID- 14587191
TI  - [Early consequent blood pressure lowering is the goal. The "blood vessel clock
      ticks" in prediabetic state].

PMID- 14587192
TI  - [Corner points of antihypertensive therapy in prediabetic state. Success with a
      combination].

PMID- 14587193
TI  - [5-alpha reductase inhibitors plus alpha blockers. A combination therapy keeps a
      common disease checked].

PMID- 14587194
TI  - [The tested combination is recommended. Are 5-alpha reductase inhibitors
      interchangeable?].

PMID- 14587195
TI  - [For the first time beta blockers are in direct comparison With carvedilol weak
      hearts beat longer].

PMID- 14587196
TI  - [What happens during the bicycle riding, what is the effect of a piece of cake?
      48 hours of blood sugar measurement].

PMID- 14587197
TI  - [When the goal values are more than 20/10 mmHg distant. High blood pressure is to
      be forced down from two sides immediately].

PMID- 14587198
TI  - [Evidence-based assessment of therapeutic agents of osteoporosis.
      Bisphosphonates, SERM and basic therapy in front].

PMID- 14587199
TI  - [Therapeutic index makes easier the choice of admissible substances. No fear
      concerning cortisone].

PMID- 14587200
TI  - [Dual platelet inhibition with clopidogrel and ASS. Who profits from the
      combination?].

PMID- 14587202
TI  - Is protein or sugar better for low blood glucose?

PMID- 14587201
TI  - [Bronchial asthma. Variable treatment promises better control].

PMID- 14587203
TI  - It's time for fair Medicare reimbursement rates. Formula adjustments can reduce
      disparities among states.

PMID- 14587204
TI  - A nonspecific rash of abrupt onset. Gianotti-Crosti syndrome.

PMID- 14587205
TI  - Erectile dysfunction and vascular disease. What is the connection?
AB  - Many of your male patients may be reluctant to talk about problems they are
      having with sexual functioning. However, it is important that you routinely and
      sensitively ask about erectile dysfunction in patients as young as 40, because
      the condition may be a sign of previously undetected vascular disease. In this
      article, Dr Kolodny explores the connection with vascular disease and suggests
      ways that primary care physicians can help patients reduce their risk of both
      erectile dysfunction and potential underlying disorders.

PMID- 14587206
TI  - Prostate cancer intervention. Involving the patient in early detection and
      treatment.
AB  - Cancer screening by PSA testing is widespread in the United States, and treatment
      recommendations encourage early therapy. Yet controversy about patient care
      persists because evidence demonstrating that these approaches improve the length
      and quality of a man's life is lacking. Physicians can assist their patients by
      first providing a balanced presentation of the known risks and benefits of
      prostate cancer detection and treatment and then incorporating patient
      preferences into medical decisions. Success in shared decision making may
      increase with use of patient education materials to convey most of the time
      consuming and challenging information. At least two of the many materials
      developed can be easily administered with very few resources and independent of
      primary care encounters.

PMID- 14587207
TI  - The challenges of testosterone deficiency. Uncovering the problem, evaluating the
      role of therapy.
AB  - In addition to its relatively uncommon congenital causes, testosterone deficiency
      in men occurs in a diverse range of clinical conditions. Even healthy men are now
      known to begin experiencing progressive yet subtle declines in testosterone
      secretion after age 30. Diagnosis can be challenging, and testosterone
      replacement therapy does not alleviate all symptoms in all men. Nevertheless,
      some men can get relief with intramuscular long-acting testosterone esters,
      transdermal testosterone patches, or transdermal testosterone gel.

PMID- 14587208
TI  - Patient notes: fibrocystic breast disease.

PMID- 14587209
TI  - Global progress towards universal childhood hepatitis B vaccination, 2003.

PMID- 14587210
TI  - Inadequate plumbing systems probably contributed to SARS transmission.

PMID- 14587211
TI  - [The cardiovascular risk score and its application in the DAI study].
AB  - Aim of this study was to estimate the risk of coronary heart disease (CHD) in a
      cohort of type 2 diabetics included in the DAI study. We analysed 8200 patients,
      40-74 years of age, with no history of cardiovascular complications. The formulae
      derived from the Framingham Heart Study were used. More than 60% of the cohort
      have a high risk of CHD. Among the under-50s, only 10% have a high risk in the
      short-term but, according to the predictions at age 60, 76.8% are at high risk.
      In the age class 50-60 years 1 in 3 women and 2 in 3 men are at high risk. In
      conclusion, our group of type 2 diabetics are at high risk of CHD both in the
      short and in the long term.

PMID- 14587212
TI  - [Standardization of glycosylated hemoglobin in the context of the DAI study].
AB  - The results obtained from 85 antidiabetic centers enrolled in the DAI study are
      presented with regard to the external quality assessment scheme for
      glycohemoglobin. The materials have been prepared by a laboratory of the network
      of reference laboratories of the International Federation of Clinical Chemistry
      (IFCC). To each control a Diabetes Control and Complications Trial (DCCT)
      traceable target value was assigned. The High-Performance Liquid Chromatography
      (HPLC) methods for glycohemoglobin are used in 75% of the centers, the
      immunochemical techniques in 21% and less than 5% is using affinity
      chromatography based methods. The data collected from the laboratories who
      completed the set of measurements show that 64% of the centers are well aligned
      to the DCCT system. The reproducibility of the methods varied between 3.7 and
      5.8% (as CV, %) and has to be improved.

PMID- 14587213
TI  - [Hyperhomocysteinemia and cardiovascular risk in diabetes mellitus].
AB  - Cardiovascular disease is a major cause of death in diabetic subjects.
      Hyperglycaemia per se cannot explain this excess of risk. Several lines of
      evidence indicate that mild hyperhomocysteinemia is an independent
      atherosclerotic risk factor in general population. Hyperhomocysteinemia is not
      linked with diabetic disease per se, rather fasting homocysteine plasma levels
      largely depend on glomerular filtration rate (GFR). There is a great dial of
      controversy on the association between high homocysteine plasma levels and
      diabetic retinopathy and neuropathy. On the contrary, most of the studies confirm
      that hyperhomocysteinemia is an independent risk factor for cardiovascular
      disease associated with diabetes.

PMID- 14587214
TI  - [Macroangiopathic complications in type 2 diabetic patients seen at an Italian
      diabetes center].
AB  - A large multicenter cohort study, the DAI study, is being performed on patients
      with type 2 diabetes mellitus who are followed by diabetic care units in Italy,
      to study the prevalence and incidence of macrovascular complications. The
      reference population consists of all patients visited at the participating units
      in the period September 1998-June 1999. Patients were randomly chosen so as to
      create a sample representative of the diabetic population visited at the units.
      Overall, 201 Italian diabetic care units participated in the study and 19,570
      patients were included in the study. The prevalence of macrovascular
      complications in Italian type 2 diabetics is 15.6% (17.2% in males and 14.0% in
      females). Acute miocardial infarction was the most prevalent (7.6%) complication
      among males, while angina was more frequent (9.3%) among females.

PMID- 14587215
TI  - Dystroglycan and muscular dystrophies related to the dystrophin-glycoprotein
      complex.
AB  - Dystroglycan (DG) is an adhesion molecule composed of two subunits, alpha and
      beta, that are produced by the post-translational cleavage of a single precursor
      molecule. DG is a pivotal component of the dystrophin-glycoprotein complex (DGC),
      which connects the extracellular matrix to the cytoskeleton in skeletal muscle
      and many other tissues. Some muscular dystrophies are caused by mutations of DGC
      components, such as dystrophin, sarcoglycan or laminin-2, or also of DGC
      associated molecules, such as caveolin-3. DG-null mice died during early
      embriogenesis and no neuromuscular diseases directly associated to genetic
      abnormalities of DG were identified so far. However, DG plays a crucial role for
      muscle integrity since its targeting at the sarcolemma is often perturbed in DGC
      related neuromuscular disorders.

PMID- 14587216
TI  - Collaborative study for the calibration of a new Italian HCV RNA reference
      preparation against the international standard.
AB  - We organised a collaborative study to calibrate a new Italian reference
      preparation for HCV RNA, the ISS 0102 reagent, to be used for plasma pools
      testing. This preparation will replace the previous one, the ISS 0498 reagent, as
      we are running short of it. The ISS 0102 reagent was obtained by appropriately
      diluting an HCV RNA-positive donation. Every participant in the collaborative
      study received four coded panels, each consisting of 5 semi-logarithmic dilutions
      of the international standard, 5 semi-logarithmic dilutions of the ISS 0102, and
      2 samples of a negative plasma pool. Based on the results provided by the 22
      participating laboratories, an HCV RNA concentration of 4500 IU/ml was assigned
      to the reference material. This preparation is available free of charge to any
      laboratory upon request.

PMID- 14587217
TI  - [Nerve growth factor and brain-derived neurotrophic factor: a possible
      etiopathogenic role in sensorineural hearing loss. Preliminary data].
AB  - Nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) are
      members of a family of structurally related secreted proteins, termed
      neurotrophins, which promote and regulate the survival of many kinds of neurons
      in the peripheral nervous system. Aim of the study is to dose the serum level of
      NGF and BDNF in 8 patients affected by sensorineural hearing loss (SNHL). The
      results show that in these patients the amount of circulating NGF, but not of
      BDNF, is significantly lower in comparison to that found in age-matched controls.
      The preliminary data of the present study suggest that NGF might have a crucial
      role in the auditory pathway, promoting the survival and preventing the
      degeneration of sensorineural cells.

PMID- 14587218
TI  - Prediction of atrial fibrillation from surface ECG: review of methods and
      algorithms.
AB  - The study aims to review the mathematical methods developed for the prediction of
      atrial fibrillation by analysis of surface electrocardiographic records in
      paroxysmal or post-cardiosurgery patients. A risk stratification based on ECG
      analysis would be very useful either to optimise the prophylactic antiarrhythmic
      treatment in high risk patients, or to limit drugs administration in low risk
      subjects. The works published so far managed to achieve good results in terms of
      sensitivity and specificity. However, since these methods are not completely
      reliable yet, their clinical application is still limited. The present study is
      divided in sections about time domain, frequency domain, premature complexes
      detection, heart rate variability, and non linear ECG analysis based methods.

PMID- 14587219
TI  - Principle of responsibility in medical imaging.
AB  - Radiological and medico-nuclear procedures are an essential part of contemporary
      medicine. They employ ionising energy, differently from other imaging modalities
      such as echography or magnetic resonance. The use of ionising testing is
      therefore associated to environmental impact and definite biorisks for the
      patient and the operator. In many clinical conditions specialty guidelines accept
      the equivalence of medical information provided by "red" (ionising) and "green"
      (noionising) techniques. Medical equivalence is translated into physician freedom
      of choice. However, common sense, guidelines of Radiological Medical Societies
      and Euratom directive (incorporated in national laws, such as Italian law 187/26
      of May 2000) suggest that a "red" technique should be used only when a "green"
      alternative is not competitive.

PMID- 14587220
TI  - Multilevel analysis in health services research: a tutorial.
AB  - This article describes a well developed, but not yet widespread, statistical
      method. It presents its distinguishing characteristic (and pre-empts the
      misunderstanding that all it is about, is including predictors from more than one
      level). It walks the reader through a simplified example: how can multilevel
      analysis be used to explain variances in patient satisfaction with the way
      hospital work is organized. It also discusses the importance of the disciplinary
      setting for the extra benefit provided by multilevel analysis, as compared to
      traditional contextual analysis.

PMID- 14587221
TI  - Ion chromatography applications in the determination of HF, HCl, NOx, SOx on
      stationary emissions.
AB  - In this work, specific topics will be covered in order to verify an effective,
      routine application of ion chromatography as a suitable and approved technique
      for emission monitoring in the determination of HF, HCl, NOx and SOx on
      stationary emission. A review of the analytical methods as proposed by recent
      updates in Italian environmental law and the problems encountered in the
      application of this method, such us the interference due to high level of
      carbonate, high hydroxides concentration particularly on SOx and NOx absorbing
      solution, are considered in the present work. The sample treatments before the IC
      analysis, this to reduce the matrix interference due to the strong basic
      solutions used to monitor different stationary emissions, are also examined. Some
      modifications in sampling are explored to find more suitable conditions for the
      IC analysis.

PMID- 14587223
TI  - [Support for the resumption of sexual activity in the postpartum woman, a subject
      devoid of interest].
AB  - This study reports the results of an Italian sampling survey carried out in 1999
      on the evaluation of the support and the information activities offered to women
      who delivered, with specific regard to sexual resumption and postpartum
      contraception. 1986 women have been interviewed. The response rate was 95%. Sixty
      three percent of the women reported they would use a contraceptive method at
      sexual resumption, but only 21 and 25% had the opportunity to receive adequate
      information on sexual resumption and family planning during post-delivery
      hospital stay.

PMID- 14587222
TI  - Environmental inequities and low birth weight.
AB  - The effects of environmental exposures to toxic agents, are related to different
      levels of exposure, genetic and biological susceptibility, risk perception and
      socioeconomic status (SES). In the present study we suggest that environmental
      influences on human reproduction should include investigations on SES, that can
      play an important role in embryo-foetal development. Low birth weight (LBW) is a
      risk factor for developing in adulthood coronary hearth disease, hypertension and
      type 2 diabetes. Maternal nutritional status and other hypothesis could explain
      LBW, however, environmental exposures are recognised as essential risk factors.
      Different studies evidenced an increased risk of LBW in relation to increased
      environmental air levels of particulate matter, carbon monoxide, and sulphur
      dioxide. Considering different risk possibilities and different risk perceptions,
      there is a need of a different scientific approach in which the scientific
      knowledge is connected with ethical and socioeconomic factors, for risk
      management, in order to overcome the environmental health inequities based on
      social contest.

PMID- 14587224
TI  - [Do Italian university birthing centers promote starting breast-feeding?].
AB  - This study reports the results of an Italian sampling survey carried out in 1999
      on the evaluation of the support and the information activities offered to women
      who delivered with specific regard to breast-feeding. 1986 women have been
      interviewed. The response rate was 95%. Ninety-four percent of the sample
      reported a positive attitude among breast-feeding, but only 80% breastfed her
      baby during hospital stay. Moreover only 31% had the opportunity to start breast
      feeding immediately after birth. Around 50% of women reported the quality of the
      hospital support as inadequate. The authors conclude that, even in the light of
      the present Italian law, much more could and should be done in order to promote
      and support women in breast-feeding.

PMID- 14587225
TI  - [HIV and related infections in Italian penal institutions: epidemiological and
      health organization note].
AB  - HIV and other infections represent an important health problem in Italian jails.
      In particular, HIV prevalence is high, due to the characteristics of the prison
      population, which is constituted by a large proportion of injecting drug users
      and foreigners. In addition, data from other countries suggest that risky
      behaviour are not uncommon during imprisonment, and transmission of HIV and other
      infection in this setting may also occur. Data from surveys conducted by the
      Penitentiary Authority in Italian jails show a decline of HIV seroprevalence from
      9.7% in 1990 to 2.6% in 2001. However, these data are largely incomplete and do
      not account for possible biases due to self-selection of inmates toward HIV
      serological testing or to variations in the access to screening activities. More
      accurate data, possibly obtained through anonymous unlinked surveys, are needed
      in order to better plan health services and preventive measures.

PMID- 14587226
TI  - [The psychosocial approach to the planning and implementation of vaccine trials
      for HIV infection].
AB  - The production of an effective vaccine for HIV infection is one of the major
      challenges for the third millennium public health. Here we review published
      studies addressing the issue of incentives and barriers influencing the choice to
      participate in a vaccine trial. Currently available literature clearly indicates
      the need to include psychosocial dimensions in the preparation and implementation
      of vaccine trials. The underestimation of participants' satisfaction about
      information communication may lead to non-adherence and to drop-out from the
      trials. Proper attention to communication skills of professionals involved in
      participants' enrollment and follow-up is essential to ensure trial success.

PMID- 14587227
TI  - [Methodological and regulatory features of clinical trials for behavioral and
      psychological symptoms in the course of dementia].
AB  - During the last few years there has been a growing awareness of behavioral and
      psychological symptoms of dementia (BPSD). These symptoms are usually classified
      in syndromes, which include psychosis, depression, agitation and sleep
      disturbances. BPSD have a major impact on the clinical course, prognosis and the
      quality of life of patients and caregivers. Moreover, BPSD considerably increase
      the social costs of dementia, since they often result in institutionalization.
      The therapy of BPSD was initially based on an empirical syndromic approach.
      However, in more recent years the efficacy and safety of treatments for these
      conditions have been tested in several controlled clinical trials. This paper
      addresses some of the methodological and regulatory issues that are relevant to
      the conducting of clinical trials for BPSD.

PMID- 14587228
TI  - [Suicide and attempted suicide in anorexia nervosa and bulimia nervosa].
AB  - Suicide in anorexia nervosa and bulimia nervosa is a major cause of death. Risk
      factors for suicide and attempted suicide (which in many cases results in
      successful suicide) in anorexia nervosa include: purging type, chronic disease,
      and during treatment, obsessive symptoms and drug abuse, major depression, and
      for anorexia nervosa low body mass index (BMI) at presentation. In anorexia
      nervosa suicide has been considered the first cause of death and attempted
      suicide is a serious threat to these individuals. Data concerning suicide in
      bulimia nervosa has still scarce whereas attempted suicides are easily found in
      clinical histories of patients. No doubt suicidal behavior is underestimated
      amongst patients with anorexia nervosa and bulimia nervosa. An effort to
      reconcile with subject of suicide and a better evaluation of these patients'
      psychopathology should improve suicide prevention strategies amongst these
      individuals.

PMID- 14587229
TI  - [Commentary note on the Italian translation of the Council for International
      Organizations of Medical Sciences 2002 Guidelines].
AB  - The new CIOMS International Ethical Guidelines on Biomedical Research Involving
      Human Subjects were published in August 2002. The aim of the present paper was to
      prepare a reasoned Italian translation of the guidelines. A preliminary version
      was submitted to a group of bioethicists and scientific research experts. Besides
      verifying the correctness and the adherence of the Italian version to the
      original text, a number of problematic terms were analysed. Some uncertainties
      emerged about the translation of expressions such as "ethical review committee"
      and "sponsor" and the difficulty to distinguish between "should" and "must". In
      the present globalisation era the need was apparent for a new approach to produce
      faithful translations based on a multidisciplinary approach that takes into
      account specific contexts and local peculiarities, but remains respectful to the
      original text.

PMID- 14587230
TI  - [The informed consent procedure in epidemiological research].
AB  - After a brief introduction on the beginning and subsequent developments of
      informed consent (IC), this paper analyses its ethical, legal, medical and
      scientific implications and its specific applications to epidemiological
      research. The aim is to highlight how IC principles should be fulfilled through
      different procedures responding to the ethical and scientific requirements of
      epidemiological research. At least two improper applications, in fact, can
      deprive IC of its meaning: referring to ethical principles without discernment,
      or following IC guidelines without critical evaluation. Attempts to improve IC
      procedures adapting them to specific needs and scientific developments should be
      evaluated carefully and without preconceptions.

PMID- 14587231
TI  - [Distribution of urologists in Spain: current situation and estimation of future
      needs using a predictive model].

PMID- 14587232
TI  - [Leiomyoma of the bladder. Analysis of a collection of 90 cases].
AB  - INTRODUCTION: Bladder leiomyomas (BL) are rare. Most publications regarding these
      tumours are reports of isolated cases; therefore they don't allow an evaluation
      of diagnostic and treatment procedures. MATERIAL & METHODS: We preformed a pooled
      analysis of 90 cases of BL reported in the literature. RESULTS: Mean age was 45.3
      (19 to 85 years), 68 (75.6%) were women. Filling symptoms were the most
      frequently reported (50%), followed by voiding symptoms (24.4%). Twenty four
      patients (26.7%) were asymptomatic. Tumours were endoluminal in 46 patients
      (51.1%), intramural in 27 (30%) and extravesical in 15 (16.7%). A laparotomy was
      performed in 56 patients (62.2%), with enucleation in 29 (32.2%), partial
      cystectomy in 25 (27.8%) and total cystectomy in 2 (2.2%). A transurethral
      resection was preformed in 27 (30%) and a transvaginal resection in 5 (5.6%). Two
      patients underwent conservative treatment. In 3 cases there were reports of
      recurrence and one patient got a vesicovaginal fistula. CONCLUSIONS: Although BL
      are rare, when evaluating bladder tumours, imaging techniques can make suspect of
      this neoplasm. Surgical treatment of these tumours has a very high success rate.
      Usually an enucleation or a transurethral resection is sufficient to render the
      patient tumour free, avoiding a more iatrogenic surgery.

PMID- 14587234
TI  - [Value of the diuretic isotopic renogram in the follow-up of the upper urinary
      tract after cystectomy and urinary diversion using intestine].
AB  - INTRODUCTION: In our experience we often observe urinary upper tract dilatation
      after urinari diversion with bowel. To spare useful approaches and therapeutics
      we have used diuretic renogram. MATERIAL AND METHOD: 26 patients with urinary
      diversion (Mainz II or Paduana ileal neobladder). We performance ultrasound,
      urography and diuretic renogram. RESULTS: Follow-up is between 1 y 4 years. After
      urinary diversion, 54% of the upper tracts are dilated but only 39.3% of them are
      obstructed in the diuretic renogram. Normal urographic tracts are normal or have
      good response in the diuretic renogram. Results goes on in the time. CONCLUSIONS:
      Diuretic renogram is a useful tool in the diagnosis of upper urinary tract
      obstruction after urinary diversion.

PMID- 14587233
TI  - [Comparative study of the expression of p53, Ki-67, bcl-2 and CK20 in superficial
      transitional carcinoma of the bladder: correlation with recurrence, histological
      grade, and clinical stage].
AB  - OBJECTIVE: We examined the presence of p53, Ki-67, bcl-2 and CK20, as detected by
      immunohistochemistry, and correlated with the classic variables (grade, stage and
      recurrence). MATERIAL AND METHOD: The authors evaluated 57 superficial
      transitional cell carcinomas. Biopsy specimens examined included non recurrent
      transitional cell carcinomas (n = 36) and recurrent transitional cell carcinomas
      (n = 21). Association of bcl-2, p53, Ki-67 y CK20 index immunoreactivity with
      tumor grade, clinical stage and tumor recurrence was examined. RESULTS: Ki-67 and
      p53 expression were related to the degree of differentiation and recurrence of
      the disease. bcl-2 and CK20 were not correlated with grade, stage and recurrence
      of the disease. CONCLUSIONS: Positivity for Ki-67 and p53 increase with grade of
      the disease. P53 and Ki-67 are predictors of tumor recurrence for patients with
      superficial transitional cell carcinoma.

PMID- 14587235
TI  - [Inverted papillomas--cases at our service and review of the literature].
AB  - Inverted papillomas are rare tumours representing about 2.2% of all urothelial
      tumours (benign or malignant). Inverted papillomas are predominantly seen in the
      bladder but these tumours have also been described in other locations, all over
      the urinary tract. The authors report six additional cases of such tumours
      describing the individual characteristics of each case, presenting symptoms,
      treatment employed and follow up available. A review of the literature relative
      to aetiology, clinical signs and symptoms, diagnostic criteria, treatment options
      and outcome has also been carried out.

PMID- 14587236
TI  - [Double-barreled wet colostomy: analysis of a urinary diversion].
AB  - We analyse our experience in performing the wet colostomy, also called
      urocolostomy and present seven cases treated at our hospital in which this was
      used. We present: a) three women, one underwent an urocolostomy as a result of a
      myelomeningocele with urinary and fecal incontinence, another because of a pelvic
      malignancy, and the third after developing a post radiotherapy cysto-proctitis;
      b) four men, one underwent this surgical procedure as a result of a traumatic
      paraplegia with multiple urinary fistulae and neurogenic bladder, the other three
      were secondary to pelvic malignancies (two bladder and one sigmoid malignacies).
      The outcome was fine in all cases with no pyelonephritis or metabolic imbalances;
      in all cases it represented a good option for these patients.

PMID- 14587237
TI  - [Microsatellite analysis in exfoliated cells from urinary sediment. Its utility
      for the detection of bladder cancer. Comparison with urinary cytology].
AB  - INTRODUCTION: Taking into account the precocity of the genetic alterations in the
      carcinogenesis of the bladder tumors, the valuation of these changes at a level
      of 9p 21-22 by means of microsatellite markers could be useful for the diagnostic
      and follow-up. PURPOSE: To evaluate the use of microsatellite markers and the
      utility of loss of heterozigosity (LOH) and microsatellite instability (MSI) in
      exfoliated cells from urine sediment. This observation offers the possibility of
      tumor detection by examining the DNA of urinary sediment. MATERIALS AND METHODS:
      We amplified with PCR the DNA of urine and blood samples from 160 patients with
      bladder cancer. We analysed LOH/MSI in cells from urinary sediment using four
      microsatellite markers of 9p 21-22 (D9S747-D9S171-D9S162-IFNA) and one from
      chromosome 4 (D4S243). The urinary cytology was used as comparative method and
      histological examination of tissue obtained by transurethral resection (TUR) as
      reference diagnostic. We calculated the sensitivity and specificity of this
      method and if there was some correlation between stage and grade tumoral.
      RESULTS: We could use 150 samples correctly. In 111 samples we found LOH/MSI
      (sensitivity 74%). The cytology was positive only in 60 patients (sensitivity
      40%). We found a bigger number of microsatellite alterations (AM) in superficial
      tumors (sensibility 77.3% vs. 28.8% for the cytology) and these were significant
      when comparing tumors GI-II vs. GIII (MSI p < 0.001--LOH p < 0.004). The marker
      with more sensibility was D4S243 with 40%. One patient with prostate carcinoma
      and another one with chronic cystitis gave false positive results. CONCLUSIONS:
      The study of LOH/MSI in bladder tumors with 5 microsatellites markers, according
      to our results showed a sensibility of 74%. The biggest number in LOH/MSI was
      found in superficial tumors and GI-GII tumors. Although we cannot discard the
      cystoscopy study in the diagnostic and follow-up, the sensitivity of the urine
      cytology is better and could be one alternative diagnostic as a non-invasive
      procedure.

PMID- 14587238
TI  - [Pelvic recurrence of urothelial tumor, after radical cysto-prostatectomy with
      orthotopic neo-bladder].
AB  - We present a case of an urothelial tumor pelvic recurrence, five months after
      radical cystoprostatectomy. No fat infiltration was demonstrated in the
      pathological study of the transurethral resection pieces. The treatment was a
      radical cystoprostatectomy with an ileal ortothopic Hautmann type neo-bladder.
      The pathological study of the surgical piece demonstrated fat infiltration in
      some points but urethra and lymphatic nodes free.

PMID- 14587239
TI  - [Management of penile and scrotal incarceration by a metal object].
AB  - Penile incarceration requires urgent management to prevent chief wound. In this
      article we present two penile and scrotum incarceration cases happened in our
      center. We contribute to a literature revision where lots of objects are
      reported. We try to simplify the different resolution techniques.

PMID- 14587240
TI  - [Solitary lung metastasis after radical prostatectomy].
AB  - Prostate carcinoma is diagnosed in earlier phases of its evolution, but this
      carcinoma may have an unpredictible evolution. Radical treatment (surgery and
      radiotherapy) is the best treatment in clinically localized tumors. The
      biochemical failure over 5 years from the surgery is 20-50% of the patients; the
      biochemical failure over 10 years from the surgery is less frequent because of
      prognostic factors from the biologic nature of the tumor. We report a case with
      biochemical and clinical failure over 10 years from the surgery.

PMID- 14587241
TI  - [Giant retroperitoneal liposarcoma].
AB  - Liposarcoma is a malignant tumor that has an embryologic origin from mesodermal
      tissue depending on fatty tissue. Although liposarcoma is only 0.1% of all human
      neoplasms, it is the most common histology subtype of retroperitoneal soft tissue
      sarcomas. This tumor grows slowly. Diffuse abdominal pain is its most frequent
      symptom and abdominal mass is the most common sign. Aggressive surgical treatment
      is basic to get a complete resection and a local disease control. This objective
      is difficult because of the large tumor size it gets in the retroperitoneal
      location and the multiorgan involvement that require the resection of a high
      percentage of contiguous organs. We report a case of a giant retroperitoneal
      liposarcoma presenting like continuous left hemiabdominal pain because of the
      visceral compression. The right kidney was involved and suffering from renal
      vessel enlargement without renal function. There is a high probability of
      microscopic residual disease and a good follow-up of the patients is necessary as
      well as an adjuvant radiation therapy in some cases.

PMID- 14587242
TI  - [Idiopathic superinfected giant hematocele].
AB  - A 45 year old male patient is attended for a marked increase in the size of the
      left hemiscrotum totally painless. The diagnosis was haematocele, but no cause
      was found for the bleeding. Orchidectomy and complete exeresis of the tunica
      vaginalis was carried out.

PMID- 14587243
TI  - [Sarcomatoid carcinoma of the kidney. Report of a new case and review of the
      bibliography].
AB  - We report a new case of sarcomatoid renal cell carcinoma, in a male of 67 years
      old, with locoregional recidive four months after first surgery, with two
      episodes of retroperitoneal hemorrhage after second surgery. The objective of
      this work is to contribute a new case and of doing one revision.

PMID- 14587245
TI  - [Sequelae of breech delivery from the aspect of physiatrics].

PMID- 14587244
TI  - [Fibroepithelial polyp of the urethra in an adult].
AB  - We present the case of a fibroepithelial polyp of the prostatic urethra in a
      forty-five year old patient. This type of polyp is rare in the adult. The
      principal symptoms which the patient presented were haematuria and an
      intermittent reduction in micturitional flow. Endoscopic images of the tumour are
      shown and certain details of its histology; this is a polypoid lesion of loose
      connective tissue covered by typical urothelium, with occasional fascicles of
      smooth muscle, no prostatic-type glandular structures and no appreciable
      inflammatory component.

PMID- 14587246
TI  - Ovarian conservation and repositioning in radical hysterectomy performed for
      cervical cancer: experimental and clinical observations.
AB  - The author presented an experimental procedure of subperitoneal respositioning of
      the ovaries into the region of abdominal wall associated with conservation of
      infundibulopelvic ligament, in female dogs. Relaparatomy was performed a year
      later. There were no significant changes in ovaries displaced both
      subperitoneally and subcutaneously. In seven patients under 36 years of age, who
      underwent the surgical procedure of radical hysterectomy for cervical cancer,
      ovaries were repositioned intraperiotoneally into the region of lower rim of the
      kidney associated with conservation of vascularization across the
      infundibulopelvic ligament. One patient presented with a cystic degeneration of
      the right ovary, whereas the others presented with normal ultrasonographic
      findings. Urinary estrogen values, estimated a year following the surgical
      procedure, ranged within normal values.

PMID- 14587247
TI  - [Regional metastases of squamous cell carcinoma of the lower lip].
AB  - INTRODUCTION: Lower lip squamous cell carcinoma is the most common oral
      carcinoma. In relation to other oral carcinomas, it has a better clinical course.
      If regional metastases appear, lower lip carcinoma has a very poor prognosis.
      METHODS: This study included patients treated for lower lip squamous cell
      carcinoma in the period 1984-2001. We examined neck metastases and time of their
      appearance after operation of the primary neoplasm. RESULTS: Our retrospective
      study included 305 patients with lower lip carcinoma in a twelve-year period. Out
      of this number, 293 had no positive neck lymph nodes, and only 12 patients had
      (4%). More than 75% of metastases appeared in the first year after surgery of the
      primary neoplasm. Contra-lateral metastases were most common. CONCLUSION: Taking
      into consideration the percentage of metastases, particularly during the first
      year after surgery, we suggest identification of sentinel lymph nodes and
      depending on PH finding one should decide about the type of neck operation.
      Frequent check-ups are necessary, especially during the first year.

PMID- 14587248
TI  - Neuron-specific enolase in cerebrospinal fluid and plasma of patients with acute
      ischemic brain disease.
AB  - The objective of this research was to determine the dynamics of change of neuron
      specific enolase concentration in patients with acute ischemic brain disease in
      cerebrospinal fluid and plasma. The study included 103 patients, their mean age
      58-66 years. The control group consisted of 16 patients, of matching age and sex,
      with radicular lesions of discal origin, subjected to diagnostic radiculography.
      Concentration of neuron-specific enolase was measured by a flouroimmunometric
      method. The results showed that the concentration of neuron-specific enolase in
      cerebrospinal fluid and plasma of patients with brain ischemic disease within
      first seven days significantly increased compared to the control. The highest
      increase of concentration was established in brain infarction, somewhat lower in
      reversible ischemic attack, and the lowest in transient ischemic attack. Maximal
      concentration was established on the 3rd-4th day upon the brain infarction.
      Neuron-specific enolase concentration in cerebrospinal fluid and plasma may be an
      indicator of pathophysiological processes in the acute phase of brain ischemia
      and is significant in early diagnostics and therapy of the disease.

PMID- 14587249
TI  - [Effect of hypoxic stress on the medullary arteries of the adrenal glands].
AB  - INTRODUCTION: It is known that suprarenal glands consist of two parts: cortex and
      medulla. Functional properties of circulation in these two parts are still
      unknown. This is a very important problem, but only a few studies have dealt with
      it, whereas full attention should be paid to the problem in future researches.
      MATERIAL AND METHODS: The experiment included 100 sexually experienced male rats
      which were exposed to hypoxia in testing chambers imitating conditions at 7000 m
      above sea level. In order to study blood vessels, we used a mixture of indian ink
      and 10% solution of gelatin and injected it into the left heart ventricle.
      RESULTS AND DISCUSSION: The most outstanding finding pointed to existence of wide
      ischemic areas in the outer portion of zona fasciculata, along with simultaneous
      strong dilatation and increased number of medullary arteries. Therefore, a
      conclusion can be made that the number of opened medullary arteries in the
      suprarenal gland depends on functional conditions and needs of the organism. The
      method used to present our results showed that vascular network of the suprarenal
      glands changed dynamically under experimental conditions. CONCLUSION: The
      obtained results point to functional accommodation of vascular network of
      suprarenal glands affected by stress, whereas medullary arteries are of
      predominantly functional character.

PMID- 14587250
TI  - [Characteristics of the voice in patients with glottic carcinoma evaluated with
      the RBH (Roughness, Breathiness, Hoarseness) and GIRBAS (Grade, Instability,
      Roughness, Breathiness, Asthenia, Strain) scales].
AB  - INTRODUCTION: Subjective voice analysis represents a diagnostic tool in phoniatry
      and is a part of everyday practice if a phoniatrist has a "trained ear". MATERIAL
      AND METHODS: This clinical prospective study included a sample of 20 male
      patients with malignant tumors involving one vocal cord-right or left. All
      patients underwent otorhinolaryngological and phoniatric examinations. Subjective
      acoustic analysis was done when patients pronounced numbers from 1 to 10.
      Afterwards, voice quality was evaluated separately by two professionals using a 4
      levels scale: RBH scale (roughness-breathiness-hoarseness) and GIRBAS scale
      (grade-instability-roughness-breathiness-asthenia-strain). RESULTS: 60% of
      patients presented with vocal cord immobility. Subjective acoustic analysis
      revealed hoarseness in 100% of patients (the most frequent value was Mod = 3
      intense hoarseness in 45% patients). Instability existed in 100% of patient (40%
      moderate, 40% intense). Strained voice existed in 100%, most frequently intense
      (45%). CONCLUSIONS: All patients with glottic carcinoma presented with
      hoarseness, strain and instability of phonation. Non vibration of vocal cord
      significantly affects the degree of dysphonia, roughness, strain and instability.
      Aerodycnamic changes affect voice hoarseness. RBH scale is simple, but GIRBAS
      scale described more psyhoacoustic phenomena most important in patients with
      glottic carcinoma.

PMID- 14587251
TI  - [Emotional stress as an illness-related factor].
AB  - INTRODUCTION: Emotions represent reactions of living organisms to changes of
      one's inner sphere, as well as to different factors from our surroundings.
      Emotions manifest in many ways. Failing to fulfill one's needs on chronic or
      acute basis leads to conflict situations. These needs may be either biological or
      social. Conflict situations occur prior to stress itself. EMOTIONAL STRESS:
      Modern technology development provides no friendly environment for workers, with
      many consequences causing psychosomatic disorders. Researches have been made to
      evaluate the amount of inflicted stress on patients. One of successful theories
      regarding this question is the theory of functional systems. The idea was to
      quantify processes of everyday living. PROPHYLAXIS AND REHABILITATION OF PERSONS
      EXPOSED TO EMOTIONAL STRESS: The primary goal was to measure one's adaptation
      abilities. In order to follow up these parameters a machine was created. This
      appliance can determine the level of stress, by measuring certain physiological
      parameters. That is way scientists may apply preventive measures in order to
      increase stress resistance. CONCLUSION: We differ hereditary and individual
      resistance to stress factors. That is why it is necessary to assess each patient
      individually. This type of individual approach offers an opportunity to create a
      specific program, in order to increase stress resistance.

PMID- 14587252
TI  - [Adrenocortical hypertension].
AB  - INTRODUCTION: Endocrine hypertension is almost exclusively adrenal hypertension
      which includes syndromes of mineralocorticoid, glucocorticoid and amine excess.
      ALDOSTERONISM: Although primary aldosteronism accounts for less than 1% of
      hypertensive population, it is the most common form of endocrine hypertension and
      the second most common form of curable hypertension. It is possible that load in
      type 2 diabetes mellitus and cardiovascular fibrosis is related to aldosteronism.
      DIAGNOSIS OF PRIMARY ALDOSTERONISM: The conventional approach to low plasma
      potassium level in hypertensive patients suggests mineralocorticoid excess,
      whereas high aldosterone level and chronically suppressed plasma renin activity
      (PRA) are basic for the diagnosis of primary aldosteronism. However, recent
      studies use the ratio of plasma aldosterone to plasma renin activity (ARR) in
      plasma. DIFFERENTIAL DIAGNOSIS: Differential diagnosis between idiopathic
      aldosteronism (IHA) and aldosterone--producing adenoma (APA) can be performed
      using postural testing, 18-hydro- xycorticosterone levels, adrenal computed
      tomograms, iodocholesterol scans and adrenal venous sampling. GLUCOCORTICOID
      HYPERTENSION: However, association between glucocorticoid excess and hypertension
      is complex and still poorly understood. Hypothesized mechanisms include:
      increased hepatic angiotensinogen synthesis, inhibition of vasodilator and
      stimulation of vasoconstrictor systems in vascular tissue, enhanced
      glucocorticoid-mediated vascular reactivity to noradrenaline, shifting of sodium
      and fluid from intracellular to extracellular compartment, and increase of local
      endothelial growth factor activity.

PMID- 14587253
TI  - [Effect of proteinuria on tubulointerstitial damage].
AB  - INTRODUCTION: Glomerular basal membrane represents a mechanical and electric
      barrier for plasma proteins. In physiological conditions only plasma proteins of
      low molecular weight are completely filtered through basal membrane. Due to
      damages of glomerular basal membrane there is an increase in filtration of plasma
      proteins of moderate and high molecular weight. PROTEINURIA: In regard to its
      etiology proteinuria can be prerenal, renal and postrenal. By analyzing albumin,
      1-microglobulin, immunoglobulin G and 2-macroglobulin, together with total
      protein in urine, it is possible to detect and differentiate causes of prerenal,
      glomerular, tubular and postrenal proteinuria. Abnormal glomerular permeability
      to macromolecules results in excessive protein delivery and reabsorption in
      proximal tubules. Excessive reabsorption in turn may cause congetion of
      intracellular endocytic and biosynthetic compartments leading to NFkB-dependent
      and -independent gene upregulation. Among those genes, monocyte chemoattractant
      protein-1 (MCP-1), cytokines, osteopontin and endothelin stimulate processes of
      interstitial inflammation and fibroblast proliferation and are ultimately
      responsible for enhanced extracellular matrix deposition and renal scarring.
      Human tubular cells exposed to albumin and HDL increase production of endothelin
      1. Endothelin-1 affects microcirculation and fibroblasts and is a monocyte
      chemoattractant. Specific proteins that are cytotoxic are transferrin/iron, low
      density lipoprotein, and complement components, all of which appear in urine in
      proteinuric states. Adequate and early diagnosis and differentiation of
      proteinuria are of immense therapeutic importance.

PMID- 14587254
TI  - [Osteosynthesis with Kirschner wires in the treatment of dislocated supracondylar
      humeral fractures in children].
AB  - INTRODUCTION: Elbow fractures account for 7-9% of all fractures in childhood,
      while the supracondylar type is the most common (up to 70%). 84% of all
      supracondylar elbow fractures occur under the age of 10 years (most often between
      the age of 5 and 8). The aim of this study was to present the technique and
      results of treatment of supracondylar fractures with grade III fragment
      dislocation in pediatric population. Treatment included orthopedic repositioning
      and percutaneous pin fixation. MATERIAL AND METHODS: Over the period 1991-2000,
      255 patients were hospitalized due to supracondylar fracture of the humerus with
      grade III fragment dislocation at the Pediatric Surgery Clinic in Novi Sad. All
      patients were aged 3-15 years. Orthopedic repositioning and percutaneous pin
      fixation under X-ray control was performed in 243 patients (95.29%). RESULTS:
      This study included 167 (65.5%) patients with full documentation. Extensor type
      of fracture was verified in 151 patients (90.42%). Male patients predominated
      over female patients--119:48. The average follow-up period was 4, 5 months. On
      the basis of clinical examination, and after completed rehabilitation,
      satisfactory results were obtained in 158 patients (94.6%), while in 9 patients
      the final outcome was unsatisfactory. DISCUSSION: Literature analysis points to
      advantages of orthopedic repositioning and percutaneous pin fixation, with
      certain modifications in the treatment of supracondylar elbow fractures with
      grade III dislocation. CONCLUSIONS: Obtained results of treatment, advantages of
      this procedure, and our experience, suggest that orthopedic repositioning and
      percutaneous pin fixation is a procedure of choice in treatment of supracondylar
      elbow fractures with third III dislocation in children.

PMID- 14587255
TI  - [Production and therapeutic use of rhenium-186, 188--the future of
      radionuclides].
AB  - INTRODUCTION: In contemporary nuclear medicine, alpha, pure beta or beta-gamma
      emitters are used for targeted therapy. Use of pure and combined alpha/beta
      emitters in oncology, endocrinology, rheumatology and, a short while ago,
      interventional cardiology, has refined as an important alternative to more common
      therapeutic regimens. Two radioisotopes of rhenium, rhenium-186 and rhenium-188,
      are of particular interest. PRODUCTION OF RHENIUM-186 AND RHENIUM-188: Rhenium
      186 is routinely produced in nuclear reactors by direct neutron activation of
      metallic rhenium enriched with 185Re via 185Re(n,) 186Re nuclear reaction. For
      production of 188Re the target is 186W. 188W is produced by double neutron
      capture which gives 188Re due to beta decay. Separation of 188Re is performed in
      generators by column chromatography, extraction or by gel technology. The best
      results are obtained using chromatographic 188W/188Re generator in which 188W is
      adsorbed on aluminium. Rhenium-188 is eluted in saline solution.
      RADIOPHARMACEUTICALS LABELED WITH RHENIUM RADIOISOTOPES AND THEIR CLINICAL
      APPLICATIONS: There are several fields of applications of radiopharmaceuticals
      labeled with 186,188Re. For bone pain palliation the most often used are 186Re
      HEDP and 188Re-DMSA. For synovectomy, 186Re-sulphide in kit form is already
      commercially available. Endovascular radiation therapy is performed by using
      188Re-perrhenate or 188Re-MAG3. Labeling of peptides and antibodies with 188Re is
      also reported. Application of rhenium radiosotopes depends on their specific
      activity. Rhenium-186,188 of low specific activity can be used only for labeling
      of particles or diphosphonates. However, labeling of peptides or antibodies can
      be performed only by using 188Re of high specific activity. CONCLUSION: 188Re is
      expected to have wide applications after development of a chromatographic
      188W/188Re generator. One of the advantages of rhenium is tis chemical similarity
      with technetium. So technetium analogues labeled with 186,188Re can be developed
      for several specific applications.

PMID- 14587256
TI  - [Chronic infectious mononucleosis].
AB  - INTRODUCTION: Chronic infectious mononucleosis is a clinical entity recognized 15
      years ago with clearly defined serological criteria: high titres of IgG Epstein
      Barr virus (EBV) virus capsid antigen (VCA), IgG EBV early antigen without IgG
      Epstein-Barr nuclear antigen (EBNA) antibodies. MATERIAL AND METHODS: This follow
      up study lasted for 2 years and included 100 acute infectious mononucleosis
      patients who were investigated every 6 months. Apart from physical examination we
      evaluated history, complete blood count and liver function together with 5
      commercial ELISA tests: IgM EBV VCA, IgG EBV VCA, IgG EB NA, IgG EBV EA and IgA
      EBV EA. RESULTS: Although malaise and fatigue with cervical lymphoadenopathy were
      the most frequent symptoms, their statistical significance was most established.
      All laboratory analyses were completely normal during the follow-up period, but
      there were four patients with acute hepatitis due to hepatitis A virus and
      adenoviruses. After 6 months of acute illness, two patients without IgG EB NA
      antibodies who were candidates for chronic disease, presented no other
      serological findings for chronic disease. It was confirmed that they had delayed
      serological response due to EBV infection, because one year later they had a
      completely normal immune status on EBV infection. CONCLUSION: Chronic infectious
      mononucleosis seems to be an extraordinary event after acute disease. This
      conclusion corresponds with literature reports of sporadic cases of this disease.

PMID- 14587257
TI  - [Occurrence of congenital malformations in dead fetuses and neonates autopsied
      between 1991 and 2001 at the Institute of Pathology and Histology in Novi Sad].
AB  - INTRODUCTION: Congenital malformations are morphological developmental anomalies
      visible during clinical examination or autopsy (in case of death, stillborn or
      abortion). Their incidence in human population is estimated to be between 5-10%,
      and perinatal mortality rate varies from 20-25%. MATERIAL AND METHODS: The
      research was conducted at the Department of Pathology and Histology and at the
      Department of Obstetrics and Gynecology in Novi Sad. We analyzed autopsy reports
      of newborns (under 28 days old), stillborns and miscarried fetuses in 1991 and
      2001. Data on type and incidence of malformations in 1991 and 2001 were compared
      in order to determine statistically significant differences. RESULTS: Autopsy
      reports for 1991 revealed malformations in 21 cases, whereas autopsies were
      performed in 103 fetuses and newborns. The total number of deliveries at the
      Department of Obstetrics and Gynecology in Novi Sad was 6,160. Autopsy reports
      for 2001 revealed malformations in 33 cases, and autopsies were performed in 126
      fetuses and newborns. The total number of deliveries at the Department of
      Obstetrics and Gynecology in Novi Sad was 6,101. Comparison regarding incidence
      of malformations in 1991 and 2001, showed no statistically significant
      difference. DISCUSSION: Congenital malformations are the most important cause of
      prenatal and perinatal mortality and morbidity. One reason for that is better
      treatment of other diseases, but on the other side, there are more toxic
      materials in human environment. CONCLUSION: It is concluded that the incidence of
      congenital malformations in mortality of fetuses and newborns is high (20.39% in
      1991, and 26.19% in 2001). We can also point to increase of central nervous
      system malformations in comparison with malformations of other organ systems.

PMID- 14587258
TI  - [Case report: parathyroid gland adenoma].
AB  - INTRODUCTION: Primary hyperparathyroidism is a generalized disorder resulting
      from excessive secretion of parathyroid hormone involving one or more parathyroid
      glands. Both familial and sporadic forms exist. Histologic examination reveals
      parathyroid adenoma in about 90% of patients, although it is sometimes difficult
      to distinguish an adenoma from a normal gland. Primary hyperparathyroidism is
      commonly characterized by hypercalcemia, hypophosphatemia and excessive bone
      resorption. CASE REPORT: This is a case report of a 52-year old female patient
      with toxic thyroid adenoma and a parathyroid gland adenoma. The patient underwent
      partial thyroidectomy as a method of choice in treatment of toxic thyroid
      adenoma. Two years later, clinical hyperparathyroidism caused by an adenoma of
      parathyroid gland has manifested and was surgically removed. DISCUSSION AND
      CONCLUSION: In mild hypercalcemia, many patients are asymptomatic and this
      condition is frequently discovered accidentally during routine laboratory
      screening. In order to provide operative treatment efficiency in thyroid nodule
      cases, besides thyroid gland morphological diagnostics, it is necessary to
      perform a preoperative verification of parathyroid glands as well. This
      diagnostic approach is essential in identifying possible simultaneous occurrence
      of multiple diseases, such as: thyroid and adenoma of parathyroid gland, in order
      to diminish incorrect diagnostic estimates.

PMID- 14587259
TI  - [Pseudomembranous colitis during antibiotic therapy].
AB  - INTRODUCTION: The use of antibiotics is commonly accompanied by diarrhea:
      idiopathic diarrhea with a benign process and diarrhea caused by Clostridium
      difficile and pseudomembranous colitis. Clostridium difficile colonizes the
      gastrointestinal tract and produces a toxin in cases when normal flora is
      suppressed by antibiotics. Pseudomembranous colitis most frequently appears after
      application of clindamycin, lincomycin, ampicillin, cephalosporins and other
      antibiotics. Diagnosis is established after rectoscopic findings of adherent
      pseudomembrane and pathohistological verification. The diagnosis is confirmed if
      there is evidence of Cl. difficile toxin in feces. CASE REPORT: We report about
      the clinical course of two patients with antibiotic-associated colitis. The
      diagnosis were made by clinical examinations, rectoscopy and pathohistologic
      verification of biopsy specimen of the intestinal mucosa. Neutralization test was
      not done due to technical reasons. Patients were treated with metronidazole.
      Unwanted side-effects of metronidazole therapy were not observed. DISCUSSION:
      Both our patients confirmed that they previously used different antibiotics. In
      the first case, diarrhea appeared during the antibiotic therapy, and in the
      second case, after finishing it. After antibiotic use, diarrhea appears in 5.30%
      cases, but fortunately pseudomembranous colitis is rare. However, taking into
      consideration that pseudomembranous colitis has a severe course and requires
      urgent treatment, one has to consider the possibility of pseudomembranous colitis
      when diarrhea appears during and after antibiotic use in order to initiate
      adequate therapy.

PMID- 14587260
TI  - [Development of midwifery in Vojvodina].
AB  - This paper deals with the beginnings and development of midwifery services as
      well as schooling modalities and professional education of midwives in Vojvodina
      after gaining freedom from Turkish rule. Obstetrical services in the Military
      Border Region of Vojvodina were much better organized than in the civil, so
      called "provincial" part. In the second half of the 18th century, law regulations
      were brought and only midwives with certificates of universities and training
      courses of special midwifery schools in bigger towns could practice midwifery. At
      that time most trained midwives in Vojvodina were of German nationality, because
      Serbs knew neither German nor Hungarian and could not get education in Vienna and
      Budapest. A century later the situation was practically the same. Dr. Svetozar
      Maksimovic, Master of Obstetrics and the first director of the Maternity Hospital
      and a city physician in Novi Sad, was well aware that this town had no midwifery
      service. That is why on July 27, 1879 he submitted a suggestion for foundation of
      a "Government Training Institute for Midwives and Pregnant Women". Although this
      suggestion was not realized, it was the first attempt to establish a school for
      midwives in Novi Sad in Serbian language and was of great importance fir history
      of medicine in Vojvodina, especially in Novi Sad. Furthermore, it points to the
      fact that physicians in Novi Sad, especially Dr. Svetozar Maksimovic, were
      informed about current medicine in the world. In the frame of public health
      special attention was paid to Women's Care Services concerning especially
      pregnancy, delivery and puerperium. However, it was not possible to realize his
      vision in Vojvodina at that time, due to insufficient number of trained midwives.

PMID- 14587261
TI  - [Peter C Lauterbur and Peter Mansfield. Winners of the 2003 Nobel Prize in
      medicine or physiology. Magnetic resonance imaging--a breakthrough in clinical
      medicine and research].

PMID- 14587262
TI  - [Emergency internal medicine in the melting-pot].

PMID- 14587263
TI  - [Long-term effect of clopidogrel do exist--but hardly worth the costs].

PMID- 14587264
TI  - [Clopidogrel before and after percutaneous coronary intervention: the PCI-CURE
      and CREDO studies do not support long-term therapy. Shorter treatment saves
      millions].
AB  - The ideal time to start treatment with clopidogrel prior to a percutaneous
      coronary intervention, the most efficacious loading-dose and the optimal duration
      of treatment following the procedure are not known in detail. PCI-CURE and CREDO
      both support pre-treatment with clopidogrel. Extended treatment beyond the first
      few months after the procedure is not, however, supported by the data.
      Accordingly, 300 mg clopidogrel should be given at least 6 hours and ideally 12
      hours before the procedure. If the intervention must be undertaken sooner, a
      doubling of the loading-dose is recommended. After the procedure, clopidogrel 75
      mg once daily should be continued for one to three months.

PMID- 14587265
TI  - [The CREDO study has obvious shortages. More belief, less knowledge].

PMID- 14587266
TI  - [The Jacobs index--a simple way to determine malignancy of pelvic tumors in
      women].

PMID- 14587267
TI  - [A potential organ donor--a new indication for intensive care?].

PMID- 14587268
TI  - [Community emergency centers important part of health care in Skane].

PMID- 14587269
TI  - [Who is responsible for mistakes? You are chief physician].

PMID- 14587270
TI  - [Patient's right to know and the public's confidence in medical ethics].

PMID- 14587271
TI  - [A verdict from the EU tribunal can make Swedish waiting lists shorter!].

PMID- 14587272
TI  - [It is easy to defend conversation as therapeutic method if the method is
      scientifically evaluated].

PMID- 14587274
TI  - [Ignorance concerning herbs--Sweden is not USA].

PMID- 14587273
TI  - [Gradual dose reduction can overcome withdrawal symptoms].

PMID- 14587275
TI  - [Let physicians to make decisions concerning sickness certificates].

PMID- 14587276
TI  - [Too many calories and too little exercise cause obesity not intake of fat].

PMID- 14587278
TI  - Structural basis of matrix metalloproteinase function.
AB  - The matrix metalloproteinases (MMPs) constitute a family of multidomain zinc
      endopeptidases which contain a catalytic domain with a common metzincin-like
      topology. The MMPs are involved not only in extracellular matrix degradation, but
      also in a number of other biological processes. Normally, their proteolytic
      activity is regulated precisely by their main endogenous protein inhibitors, in
      particular the tissue inhibitors of metalloproteinases (TIMPs). Disruption of
      this balance results in serious diseases, such as arthritis, tumour growth and
      metastasis, rendering the MMPs attractive targets for inhibition therapy.
      Knowledge of their tertiary structures is crucial for a full understanding of
      their functional properties. Since the first publication of atomic MMP structures
      in 1994, much more structural information has become available on details of the
      catalytic domain, on its interaction with synthetic and protein inhibitors, on
      domain organization and on the formation of complexes with other proteins. This
      review will outline our current knowledge of MMP structure.

PMID- 14587277
TI  - A tribute to Alan J. Barrett.

PMID- 14587279
TI  - Papain-like lysosomal cysteine proteases and their inhibitors: drug discovery
      targets?
AB  - Papain-like lysosomal cysteine proteases are processive and digestive enzymes
      that are expressed in organisms from bacteria to humans. Increasing knowledge
      about the physiological and pathological roles of cysteine proteases is bringing
      them into the focus of drug discovery research. These proteases have rather short
      active-site clefts, comprising three well defined substrate-binding subsites (S2,
      S1 and S1') and additional broad binding areas (S4, S3, S2' and S3'). The
      geometry of the active site distinguishes cysteine proteases from other protease
      classes, such as serine and aspartic proteases, which have six and eight
      substrate-binding sites respectively. Exopeptidases (cathepsins B, C, H and X),
      in contrast with endopeptidases (such as cathepsins L, S, V and F), possess
      structural features that facilitate the binding of N- and C-terminal groups of
      substrates into the active-site cleft. Other than a clear preference for free
      chain termini in the case of exopeptidases, the substrate-binding sites exhibit
      no strict specificities. Instead, their subsite preferences arise more from the
      specific exclusion of substrate types. This presents a challenge for the design
      of inhibitors to target a specific cathepsin: only the cumulative effect of an
      assembly of inhibitor fragments will bring the desired result.

PMID- 14587280
TI  - Roles for asparagine endopeptidase in class II MHC-restricted antigen processing.
AB  - The adaptive immune response depends on the creation of suitable peptides from
      foreign antigens for display on MHC molecules to T lymphocytes. Similarly, MHC
      restricted display of peptides derived from self proteins results in the
      elimination of many potentially autoreactive T cells. Different proteolytic
      systems are used to generate the peptides that are displayed as T cell epitopes
      on class I compared with class II MHC molecules. In the case of class II MHC
      molecules, the proteases that reside within the endosome/lysosome system of
      antigen-presenting cells are responsible; surprisingly, however, there are
      relatively few data on which enzymes are involved. Recently we have asked whether
      proteolysis is required simply in a generic sense, or whether the action of
      particular enzymes is needed to generate specific class II MHC-associated T cell
      epitopes. Using the recently identified mammalian asparagine endopeptidase as an
      example, we review recent evidence that individual enzymes can make clear and non
      redundant contributions to MHC-restricted peptide display.

PMID- 14587281
TI  - Substrate specificity and inducibility of TACE (tumour necrosis factor alpha
      converting enzyme) revisited: the Ala-Val preference, and induced intrinsic
      activity.
AB  - Tumour necrosis factor alpha (TNF alpha)-converting enzyme (TACE/ADAM-17, where
      ADAM stands for a disintegrin and metalloproteinase) releases from the cell
      surface the extracellular domains of TNF and several other proteins. Previous
      studies have found that, while purified TACE preferentially cleaves peptides
      representing the processing sites in TNF and transforming growth factor alpha,
      the cellular enzyme nonetheless also sheds proteins with divergent cleavage sites
      very efficiently. More recent work, identifying the cleavage site in the p75 TNF
      receptor, quantifying the susceptibility of additional peptides to cleavage by
      TACE and identifying additional protein substrates, underlines the complexity of
      TACE-substrate interactions. In addition to substrate specificity, the mechanism
      underlying the increased rate of shedding caused by agents that activate cells
      remains poorly understood. Recent work in this area, utilizing a peptide
      substrate as a probe for cellular TACE activity, indicates that the intrinsic
      activity of the enzyme is somehow increased.

PMID- 14587282
TI  - Meprin proteolytic complexes at the cell surface and in extracellular spaces.
AB  - Meprins are metalloproteinases of the astacin family and metzincin superfamily
      that are composed of evolutionarily related alpha and beta subunits, which exist
      as homo- and hetero-oligomeric complexes. These complexes are abundant at the
      brush border membranes of kidney proximal tubule cells and epithelial cells of
      the intestine, and are also expressed in certain leucocytes and cancer cells.
      Meprins cleave bioactive peptides such as gastrin, cholecystokinin and
      parathyroid hormone, cytokines such as osteopontin and monocyte chemotactic
      peptide-1, as well as proteins such as gelatin, collagen IV, fibronectin and
      casein. Database predictions and initial data indicate that meprins are also
      capable of shedding proteins, including itself, from the cell surface. Membrane
      bound meprin subunits are composed of dimeric meprin beta subunits or tetrameric
      hetero-oligomeric alpha beta complexes of approx. 200-400 kDa, and can be
      activated at the cell surface; secreted forms of homo-oligomeric meprin alpha are
      zymogens that form high-molecular-mass complexes of 1-6 MDa. These are among the
      largest extracellular proteases identified thus far. The latent (self
      associating) homo-oligomeric complexes can move through extracellular spaces in a
      non-destructive manner, and deliver a concentrated form of the metalloproteinase
      to sites that have activating proteases, such as sites of inflammation, infection
      or cancerous growth. Meprins provide examples of novel ways of concentrating
      proteolytic activity at the cell surface and in the extracellular milieu, which
      may be critical to proteolytic function.

PMID- 14587283
TI  - Role of TIMPs (tissue inhibitors of metalloproteinases) in pericellular
      proteolysis: the specificity is in the detail.
AB  - Pericellular proteolysis represents one of the key modes by which the cell can
      modulate its environment, involving not only turnover of the extracellular matrix
      but also the regulation of cell membrane proteins, such as growth factors and
      their receptors. The metzincins are active players in such proteolytic events,
      and their mode of regulation is therefore of particular interest and importance.
      The TIMPs (tissue inhibitors of metalloproteinases) are established endogenous
      inhibitors of the matrix metalloproteinases (MMPs), and some have intriguing
      abilities to associate with the pericellular environment. It has been shown that
      TIMP-2 can bind to cell surface MT1-MMP (membrane-type 1 MMP) to act as a
      'receptor' for proMMP-2 (progelatinase A), such that the latter can be activated
      efficiently in a localized fashion. We have examined the key structural features
      of TIMP-2 that determine this unique function, showing that Tyr36 and Glu192
      Asp193 are vital for specific interactions with MT1-MMP and proMMP-2
      respectively, and hence activation of proMMP-2. TIMP-3 is sequestered at the cell
      surface by association with the glycosaminoglycan chains of proteoglycans,
      especially heparan sulphate, and we have shown that it may play a role in the
      regulation of some ADAMs (a disintegrin and metalloproteinases), including tumour
      necrosis factor alpha-converting enzyme (TACE; ADAM17). We have established that
      key residues in TIMP-3 determine its interaction with TACE. Further studies of
      the features of TIMP-3 that determine specific binding to both ADAM and
      glycosaminoglycan are required in order to understand these unique properties.

PMID- 14587284
TI  - Collagen-platelet interactions: recognition and signalling.
AB  - The collagen-platelet interaction is central to haemostasis and may be a critical
      determinant of arterial thrombosis, where subendothelium is exposed after rupture
      of atherosclerotic plaque. Recent research has capitalized on the cloning of an
      important signalling receptor for collagen, glycoprotein VI, which is expressed
      only on platelets, and on the use of collagen-mimetic peptides as specific tools
      for both glycoprotein VI and integrin alpha 2 beta 1. We have identified
      sequences, GPO and GFOGER (where O denotes hydroxyproline), within collagen that
      are recognized by the collagen receptors glycoprotein VI and integrin alpha 2
      beta 1 respectively, allowing their signalling properties and specific functional
      roles to be examined. Triple-helical peptides containing these sequences were
      used to show the signalling potential of integrin alpha 2 beta 1, and to confirm
      its important contribution to platelet adhesion. Glycoprotein VI appears to
      operate functionally on the platelet surface as a dimer, which recognizes GPO
      motifs that are separated by four triplets of collagen sequence. These advances
      will allow the relationship between the structure of collagen and its haemostatic
      activity to be established.

PMID- 14587285
TI  - Control of the expression of inflammatory response genes.
AB  - The expression of genes involved in the inflammatory response is controlled both
      transcriptionally and post-transcriptionally. Primary inflammatory stimuli, such
      as microbial products and the cytokines interleukin-1 (IL-1) and tumour necrosis
      factor alpha (TNF alpha), act through receptors of either the Toll and IL-1
      receptor (TIR) family or the TNF receptor family. These cause changes in gene
      expression by activating four major intracellular signalling pathways that are
      cascades of protein kinases: namely the three mitogen-activated protein kinase
      (MAPK) pathways, and the pathway leading to activation of the transcription
      factor nuclear factor kappa B (NF kappa B). The pathways directly activate and
      induce the expression of a limited set of transcription factors which promote the
      transcription of inflammatory response genes. Many of the mRNAs are unstable, and
      are stabilized by the p38 MAPK pathway. Instability is mediated by clusters of
      the AUUUA motif in the 3' untranslated regions of the mRNAs. Control of mRNA
      stability provides a means of increasing the amplitude of a response and allows
      rapid adjustment of mRNA levels. Not all mRNAs stabilized by p38 contain AUUUA
      clusters; for example, matrix metalloproteinase-1 and -3 mRNAs lack these
      clusters, but are stabilized. Inflammatory gene expression is inhibited by
      glucocorticoids. These suppress MAPK signalling by inducing a MAPK phosphatase.
      This may be a significant mechanism additional to that by which the
      glucocorticoid receptor interferes with transcription factors.

PMID- 14587286
TI  - Use of anti-neoepitope antibodies for the analysis of degradative events in
      cartilage and the molecular basis for neoepitope specificity.
AB  - Degradation of the cartilage proteoglycan, aggrecan, is an essential aspect of
      normal growth and development, and of joint pathology. The roles of different
      proteolytic enzymes in this process can be determined from the sites of cleavage
      in the aggrecan core protein, which generates novel termini (neoepitopes).
      Antibodies specific for the different neoepitopes generated by such cleavage
      events provide powerful tools with which to analyse these processes. The same
      approach can be used to differentiate the processed, active forms of proteases
      from their inactive pro-forms. Since the proteolytic processing of these enzymes
      requires the removal of the inhibitory pro-region, it also results in the
      generation of N-terminal neoepitopes. Using the newborn rat long bone as a model
      system, it was shown that the active form of ADAMTS-4 [ADAM (a disintegrin and
      metalloproteinase) with thrombospondin motifs-4], but not ADAMTS-5, co-localizes
      with the aggrecan cleavage neoepitopes known to be produced by this
      metalloproteinase. Thus, in long bone growth, aggrecan turnover seems to be
      dependent on ADAMTS-4 activity. To demonstrate the molecular basis of the
      specificity of anti-neoepitope antibodies, the Fv region of a monoclonal antibody
      specific for a neoepitope generated by the ADAMTS-4-mediated cleavage of aggrecan
      has been modelled and the binding of the peptide epitope simulated. In the docked
      structure, the N-terminus of the peptide antigen is clearly buried in the binding
      site cavity. The absence of an open cleft makes it impossible for the intact
      substrate to pass through the binding site, providing a rationale for the
      specificity of this class of antibodies.

PMID- 14587288
TI  - Cytokine synergy, collagenases and cartilage collagen breakdown.
AB  - We have investigated proteinases that degrade cartilage collagen. We show that
      pro-inflammatory cytokines act synergistically with oncastatin M to promote
      cartilage collagen resorption by the up-regulation and activation of matrix
      metalloproteinases (MMPs). The precise mechanisms are not known, but involve the
      up-regulation of c-fos, which binds to MMP promoters at a proximal activator
      protein-1 (AP-1) site. This markedly up-regulates transcription and leads to
      higher levels of active MMP proteins.

PMID- 14587287
TI  - Proteolysis of the collagen fibril in osteoarthritis.
AB  - The development of cartilage pathology in osteoarthritis involves excessive
      damage to the collagen fibrillar network, which appears to be mediated primarily
      by the chondrocyte-generated cytokines interleukin-1 and tumour necrosis factor
      alpha and the collagenases matrix metalloproteinase-1 (MMP-1) and MMP-13. The
      damage to matrix caused by these and other MMPs can result in the production of
      sufficient degradation products that can themselves elicit further degradation,
      leading to chondrocyte differentiation and eventually matrix mineralization and
      cell death. Knowledge of these MMPs, cellular receptors and cytokine pathways,
      and the ability to selectively antagonize them by selective blockade of function,
      may provide valuable therapeutic opportunities in the treatment of osteoarthritis
      and other joint diseases involving cartilage resorption, such as rheumatoid
      arthritis. The ability to detect the products of these degradative events
      released into body fluids of patients may enable us to monitor disease activity,
      predict disease progression and determine more rapidly the efficacy of new
      therapeutic agents.

PMID- 14587289
TI  - Proteolytic 'defences' and the accumulation of oxidized polypeptides in
      cataractogenesis and atherogenesis.
AB  - Over the last few years, it has been clearly established that normal plasma
      contains low levels of oxidized polypeptides, and that these accumulate in
      tissues during several age-related pathologies. In contrast, normal mammalian
      aging, contrary to conventional dogma, is not clearly associated with enhanced
      levels of oxidized proteins, except in extracellular connective tissues, whose
      proteins can, for example, be oxidized by the neutrophil oxidative burst. Since
      mildly oxidized proteins are susceptible to accelerated degradation in most
      experimental systems, the question arises as to how the accumulation of oxidized
      proteins can take place. Such accumulation requires an excess of production (or
      deposition) over removal, which might reflect alterations in capacity or rate of
      production or removal. This chapter discusses our presently limited knowledge of
      rates and control of proteolysis of oxidized proteins in two pathologies,
      cataractogenesis and atherogenesis. It commences with a brief summary of current
      understanding of the mechanisms of protein oxidation, and of the observed
      accumulation of oxidized proteins in several pathologies.

PMID- 14587290
TI  - Proteases as drug targets.
AB  - The effective management of AIDS with HIV protease inhibitors, or the use of
      angiotensin-converting enzyme inhibitors to treat hypertension, indicates that
      proteases do make good drug targets. On the other hand, matrix metalloproteinase
      (MMP) inhibitors from several companies have failed in both cancer and rheumatoid
      arthritis clinical trials. Mindful of the MMP inhibitor experience, this chapter
      explores how tractable proteases are as drug targets from a chemistry
      perspective. It examines the recent success of other classes of drug for the
      treatment of rheumatoid arthritis, and highlights the need to consider where
      putative targets lie on pathophysiological pathways--regardless of what kind of
      therapeutic entity would be required to target them. With genome research
      yielding many possible new drug targets, it explores the likelihood of
      discovering proteolytic enzymes that are causally responsible for disease
      processes and that might therefore make better targets, especially if they lead
      to the development of drugs that can be administered orally. It also considers
      the impact that biologics are having on drug discovery, and in particular whether
      biologically derived therapeutics such as antibodies are likely to significantly
      alter the way we view proteases as targets and the methods used to discover
      therapeutic inhibitors.

PMID- 14587291
TI  - How serpins change their fold for better and for worse.
AB  - The serpins differ from the many other families of serine protease inhibitors in
      that they undergo a profound change in topology in order to entrap their target
      protease in an irreversible complex. The solving of the structure of this complex
      has now provided a video depiction of the changes involved. Cleavage of the
      exposed reactive centre of the serpin triggers an opening of the five-stranded A
      sheet of the molecule, with insertion of the cleaved reactive loop as an
      additional strand in the centre of the sheet. The drastic displacement of the
      acyl-linked protease grossly disrupts its active site and gives an overall loss
      of 40% of ordered structure. This ability to provide effectively irreversible
      inhibition explains the selection of the serpins to control the proteolytic
      cascades of higher organisms. The conformational mechanism provides another
      advantage in its potential to modulate activity. Sequential crystallographic
      structures now provide clear depictions of the way antithrombin is activated on
      binding to the heparans of the microcirculation, and how evolution has utilized
      this mobile mechanism for subtle variations in activity. The complexity of these
      modulatory mechanisms is exemplified by heparin cofactor II, where the change in
      fold is seen to trigger multiple allosteric effects. The downside of the mobile
      mechanism of the serpins is their vulnerability to aberrant intermolecular beta
      linkages, resulting in various disorders from cirrhosis to thrombosis. These
      provide a well defined structural prototype for the new entity of the
      conformational diseases, including the common dementias, as confirmed by the
      recent identification of the familial neuroserpin dementias.

PMID- 14587292
TI  - Cystatins.
AB  - Chicken egg white cystatin was first described in the late 1960s. Since then, our
      knowledge about a superfamily of similar proteins present in mammals, birds,
      fish, insects, plants and some protozoa has expanded, and their properties as
      potent peptidase inhibitors have been firmly established. Today, 12 functional
      chicken cystatin relatives are known in humans, but a few evolutionarily related
      gene products still remain to be characterized. The type 1 cystatins (A and B)
      are mainly intracellular, the type 2 cystatins (C, D, E/M, F, G, S, SN and SA)
      are extracellular, and the type 3 cystatins (L- and H-kininogens) are
      intravascular proteins. All true cystatins inhibit cysteine peptidases of the
      papain (C1) family, and some also inhibit legumain (C13) family enzymes. These
      peptidases play key roles in physiological processes, such as intracellular
      protein degradation (cathepsins B, H and L), are pivotal in the remodelling of
      bone (cathepsin K), and may be important in the control of antigen presentation
      (cathepsin S, mammalian legumain). Moreover, the activities of such peptidases
      are increased in pathophysiological conditions, such as cancer metastasis and
      inflammation. Additionally, such peptidases are essential for several pathogenic
      parasites and bacteria. Thus cystatins not only have capacity to regulate normal
      body processes and perhaps cause disease when down-regulated, but may also
      participate in the defence against microbial infections. In this chapter, we have
      aimed to summarize our present knowledge about the human cystatins.

PMID- 14587293
TI  - Designing TIMP (tissue inhibitor of metalloproteinases) variants that are
      selective metalloproteinase inhibitors.
AB  - The tissue inhibitors of metalloproteinases (TIMPs) are endogenous inhibitors of
      the matrix metalloproteinases (MMPs), enzymes that play central roles in the
      degradation of extracellular matrix components. The balance between MMPs and
      TIMPs is important in the maintenance of tissues, and its disruption affects
      tissue homoeostasis. Four related TIMPs (TIMP-1 to TIMP-4) can each form a
      complex with MMPs in a 1:1 stoichiometry with high affinity, but their inhibitory
      activities towards different MMPs are not particularly selective. The three
      dimensional structures of TIMP-MMP complexes reveal that TIMPs have an extended
      ridge structure that slots into the active site of MMPs. Mutation of three
      separate residues in the ridge, at positions 2, 4 and 68 in the amino acid
      sequence of the N-terminal inhibitory domain of TIMP-1 (N-TIMP-1), separately and
      in combination has produced N-TIMP-1 variants with higher binding affinity and
      specificity for individual MMPs. TIMP-3 is unique in that it inhibits not only
      MMPs, but also several ADAM (a disintegrin and metalloproteinase) and ADAMTS
      (ADAM with thrombospondin motifs) metalloproteinases. Inhibition of the latter
      groups of metalloproteinases, as exemplified with ADAMTS-4 (aggrecanase 1),
      requires additional structural elements in TIMP-3 that have not yet been
      identified. Knowledge of the structural basis of the inhibitory action of TIMPs
      will facilitate the design of selective TIMP variants for investigating the
      biological roles of specific MMPs and for developing therapeutic interventions
      for MMP-associated diseases.

PMID- 14587294
TI  - Memapsin 2, a drug target for Alzheimer's disease.
AB  - Mempasin 2, a beta-secretase, is the membrane-anchored aspartic protease that
      initiates the cleavage of amyloid precursor protein leading to the production of
      beta-amyloid and the onset of Alzheimer's disease. Thus memapsin 2 is a major
      therapeutic target for the development of inhibitor drugs for the disease. Many
      biochemical tools, such as the specificity and crystal structure, have been
      established and have led to the design of potent and relatively small transition
      state inhibitors. Although developing a clinically viable mempasin 2 inhibitor
      remains challenging, progress to date renders hope that memapsin 2 inhibitors may
      ultimately be useful for therapeutic reduction of beta-amyloid.

PMID- 14587295
TI  - Control of lipid metabolism by regulated intramembrane proteolysis of sterol
      regulatory element binding proteins (SREBPs).
AB  - In mammalian cells, the supply of lipids is co-ordinated with demand through the
      transcriptional control of genes encoding proteins required for synthesis or
      uptake. The sterol regulatory element binding proteins (SREBPs) are responsible
      for increased transcription of these genes when lipid level fall. Mammals have
      three SREBPs (-1a, -1c and -2), which are the products of two distinct genes.
      Synthesized as approximately 120 kDa precursors, they are inserted into membranes
      of the endoplasmic reticulum (ER) in a hairpin fashion. Both the N-terminal
      transcription factor domain and the C-terminal regulatory domain face the
      cytoplasm. These are connected by two transmembrane helices separated by a short
      loop projecting into the ER lumen. The C-terminal domain of SREBP interacts with
      the C-terminal domain of SREBP-cleavage-activating protein (SCAP). The N-terminal
      half of SCAP contains eight transmembrane helices, five of which (helices 2-6)
      form the sterol-sensing domain. In response to cellular demand for lipid, this
      complex exits the ER and transits to the Golgi apparatus, where two distinct
      proteases cleave the SREBP precursor to release the transcriptionally active N
      terminus. This process was the first example of regulated intramembrane
      proteolysis for which the proteases were identified. Recent work has additionally
      uncovered integral membrane proteins, insig-1 and insig-2, that are required to
      retain the SREBP-SCAP complex in the ER in the presence of sterols, thus
      providing a more complete understanding of the control of proteolysis in this
      complex regulatory pathway.

PMID- 14587296
TI  - Caspase activation.
AB  - Caspase activation is the 'point of no return' commitment to cell death.
      Synthesized as inactive zymogens, it is essential that the caspases remain
      inactive until the death signal is received. It is known for the downstream
      executioner caspases-3 and -7 that the activation event is proteolytic cleavage,
      and this had been assumed to apply to the initiator caspases as well. However,
      recent studies conducted on caspases-2, -8 and -9 have challenged this tenet of
      caspase activation. In this review we focus on the molecular details of caspase
      activation, with emphasis on recent work that provides a pleasing explanation for
      the differential requirements for the activation of executioner and initiator
      caspases.

PMID- 14587297
TI  - Separase regulation during mitosis.
AB  - The final, irreversible step in the duplication and distribution of genomes to
      daughter cells takes place when chromosomes split at the metaphase-to-anaphase
      transition. A protease of the CD clan, separase (C50 family), is the key
      regulator of this transition. During metaphase, cohesion between sister
      chromatids is maintained by a chromosomal protein complex, cohesin. Anaphase is
      triggered when separase cleaves the Scc1 subunit of cohesin at two specific
      recognition sequences. As a result of this cleavage, the cohesin complex is
      destroyed, allowing the spindle to pull sister chromatids into opposite halves of
      the cell. Because of the final and irreversible nature of Scc1 cleavage, this
      reaction is tightly controlled. Several independent mechanisms impose regulation
      on separase activity, as well as on the susceptibility of the cleavage target
      Scc1 to cleavage by separase. This chapter provides an overview of these multiple
      levels of regulation.

PMID- 14587298
TI  - Membrane-type 1 matrix metalloproteinase and cell migration.
AB  - Membrane-type 1 matrix metalloproteinase (MT1-MMP) is an integral membrane
      proteinase that performs processing of cell surface proteins and degradation of
      extracellular matrix (ECM) components. Through these proteolytic events, MT1-MMP
      regulates various cellular functions, including ECM turnover, promotion of cell
      migration and invasion, and morphogenic responses to extracellular stimuli. MT1
      MMP has to be regulated strictly to accomplish its function appropriately at
      various steps, including at the transcriptional and post-translational levels.
      MT1-MMP was originally identified as an invasion-promoting enzyme expressed in
      malignant tumour cells, and also as a specific activator of proMMP-2, which is
      believed to play a role in invasion of the basement membrane. Since then, it has
      attracted attention as a membrane-associated MMP that promotes cancer cell
      invasion and angiogenesis by endothelial cells. Although MT1-MMP has now become
      one of the best characterized enzymes in the MMP family, there remain numerous
      unanswered questions. In this chapter, we summarize our recent findings on how
      MT1-MMP is regulated during cell migration, and how cell migration is regulated
      by MT1-MMP.

PMID- 14587299
TI  - Cathepsin B and its role(s) in cancer progression.
AB  - Experimental and clinical evidence has linked cathepsin B with tumour invasion
      and metastasis. Cathepsin B expression is increased in many human cancers at the
      mRNA, protein and activity levels. In addition, cathepsin B is frequently
      overexpressed in premalignant lesions, an observation that associates this
      protease with local invasive stages of cancer. Increased expression of cathepsin
      B in primary cancers, and especially in preneoplastic lesions, suggests that this
      enzyme might have pro-apoptotic features. Expression of cathepsin B is regulated
      at many different levels, from gene amplification, use of alternative promoters,
      increased transcription and alternative splicing, to increased stability and
      translatability of transcripts. During the transition to malignancy, a change in
      the localization of cathepsin B occurs, as demonstrated by the presence of
      cathepsin B-containing vesicles at the cell periphery and at the basal pole of
      polarized cells. Due to increased expression of cathepsin B and changes in
      intracellular trafficking, increased secretion of procathepsin B from tumours is
      observed. Active cathepsin B is also secreted from tumours, a mechanism likely to
      be facilitated by lysosomal exocytosis or extracellular processing by surface
      activators. Cathepsin B is localized to caveolae on the tumour surface, where
      binding to the annexin II heterotetramer occurs. Activation of cathepsin B on the
      cell surface leads to the regulation of downstream proteolytic cascade(s).

PMID- 14587300
TI  - Proteolytic and non-proteolytic migration of tumour cells and leucocytes.
AB  - The migration of different cell types, such as leucocytes and tumour cells,
      involves cellular strategies to overcome the physical resistance of three
      dimensional tissue networks, including proteolytic degradation of extracellular
      matrix (ECM) components. High-resolution live-cell imaging techniques have
      recently provided structural and biochemical insight into the differential use of
      matrix-degrading enzymes in the migration processes of different cell types
      within the three-dimensional ECM. Proteolytic migration is achieved by slow
      moving cells, such as fibroblasts and mesenchymally moving tumour cells, by
      engaging matrix metalloproteinases, cathepsins and serine proteases at the cell
      surface in a focalized manner ('pericellular proteolysis'), while adhesion and
      migratory traction are provided by integrins. Pericellular breakdown of ECM
      components generates localized matrix defects and remodelling along migration
      tracks. In contrast with tumour cells, constitutive non-proteolytic migration is
      used by rapidly moving T lymphocytes. This migration type does not generate
      proteolytic matrix remodelling, but rather depends on shape change to allow cells
      to glide and squeeze through gaps and trails present in connective tissues. In
      addition, constitutive proteolytic migration can be converted into non
      proteolytic movement by protease inhibitors. After the simultaneous inhibition of
      matrix metalloproteinases, serine/threonine proteases and cysteine proteases in
      tumour cells undergoing proteolysis-dependent movement, a fundamental adaptation
      towards amoeboid movement is able to sustain non-proteolytic migration in these
      tumour cells (the mesenchymal-amoeboid transition). Instead of using proteases
      for matrix degradation, the tumour cells use leucoyte-like strategies of shape
      change and squeezing through matrix gaps along tissue scaffolds. The diversity of
      protease function in cell migration by different cell types highlights response
      diversity and molecular adaptation of cell migration upon pharmacotherapeutic
      protease inhibitor treatment.

PMID- 14587301
TI  - Demographics, treatment regimens and the use of angiotensin-receptor blockers in
      heart failure: findings from the Valsartan Heart Failure Trial.
AB  - Heart failure is the only major cardiovascular disease with an incidence and
      prevalence that continue to increase in the developed world. Early identification
      and correct treatment of the condition are of paramount importance. In recent
      years, there has been growing interest in identifying the differences between
      patients in terms of their risk of heart failure and response to treatment.
      Differences between men and women, different age groups, patients with varying
      aetiologies or comorbidities and differences between ethnic groups are only some
      of the factors that have been identified. This review surveys the available data
      on differences in responses to treatment, and discusses the use of angiotensin
      receptor blockers in heart failure in light of the recent Valsartan Heart Failure
      Trial (Val-HeFT).

PMID- 14587302
TI  - Improvement in gastric histology following Helicobacter pylori eradication
      therapy in Japanese peptic ulcer patients.
AB  - We aimed to determine if successful or failed eradication of Helicobacter pylori
      with triple therapy causes any difference in gastric mucosal histology. Japanese
      H. pylori-positive patients with a healed peptic ulcer received high (n = 112) or
      low (n = 113) doses of triple therapy (omeprazole, amoxicillin and
      clarithromycin) for 1 week. Biopsies from the greater curvature of the central
      antrum and upper corpus were taken 6 weeks and 30 weeks after treatment
      completion, and gastric mucosal histology compared between successful (n = 171)
      and failed (n = 34) eradication groups. Morphological variables of gastritis were
      graded according to the updated Sydney System. Successful eradication therapy was
      defined as improvement in inflammation, neutrophil activity and atrophy; failed
      eradication therapy as improvement in inflammation and neutrophil activity only.
      Gastric mucosal atrophy gradually improved (in addition to improvements in
      inflammation and neutrophil activity) with successful eradication of H. pylori
      infection.

PMID- 14587303
TI  - Pulse pressure responses in patients treated with Valsartan and
      hydrochlorothiazide combination therapy.
AB  - In a randomized, double-blind, parallel-group study of middle-aged and elderly
      patients, we examined the effects of treatment with the angiotensin receptor
      blocker valsartan (Val) in combination with hydrochlorothiazide (HCTZ) on pulse
      pressure (PP). After a 2-week washout period, patients entered a 4-week single
      blind Val 160 mg once daily run-in period before randomization to one of three
      treatment groups: Val 160 mg (n = 666), Val 160 mg/HCTZ 12.5 mg (n = 670) or Val
      160 mg/HCTZ 25 mg (n = 666), once daily for eight weeks. Sitting PP at baseline
      was similar in all groups. From baseline to randomization, Val monotherapy
      reduced PP by 4.7 +/- 10.2 mmHg (mean +/- SD). At the end of the study, overall
      reductions in PP were 6.7 mmHg for Val 160/HCTZ 12.5 and 7.5 mmHg for Val
      160/HCTZ 25. Val monotherapy reduced PP in mild-to-moderate hypertensive
      patients. Val combined with HCTZ provides an additional dose-related reduction in
      PP.

PMID- 14587304
TI  - The effects of haemodialysis and peritoneal dialysis on serum lipoprotein(a) and
      C-reactive protein levels.
AB  - Elevated serum lipoprotein(a) is an independent risk factor for coronary artery
      disease, and C-reactive protein (CRP) is a general and cardiovascular marker in
      haemodialysis patients. We studied lipoprotein(a) and CRP levels in 48
      haemodialysis and 24 continuous ambulatory peritoneal dialysis (CAPD) patients
      and 20 healthy individuals, after a 12 h fast. Serum lipoprotein(a) levels were
      elevated in 31.3%, 66.7% and 5% of haemodialysis and CAPD patients and control
      subjects, respectively. The difference between all groups was significant. Serum
      CRP levels were high in 43.8%, 58.4% and 5% of haemodialysis and CAPD patients,
      and healthy subjects, respectively. The mean serum CRP level was significantly
      different between all groups. Both protein levels were higher in CAPD patients
      than haemodialysis patients, suggesting that CAPD patients should be more closely
      monitored for coronary artery disease.

PMID- 14587305
TI  - Elevated serum soluble Fas levels in the various stages of hepatitis C virus
      induced liver disease.
AB  - We aimed to determine serum soluble Fas antigen (sFas) levels at various stages
      of hepatitis C virus (HCV)-induced liver disease, and investigate correlations
      between serum sFas levels and clinical, biochemical and pathologic features.
      Sixty-five patients were categorized into five groups: 1, chronic active
      hepatitis C, elevated alanine aminotransferase (ALT), HCV-polymerase chain
      reaction (PCR) positive; 2, responders to interferon + ribavirin therapy; 3,
      cirrhosis; 4, chronic hepatitis C, normal ALT, HVC-PCR positive; and 5, sustained
      responders. Group 6 comprised 15 control individuals. Serum sFas levels were
      measured by enzyme-linked immunosorbent assay. Significant differences in serum
      sFas levels were found between the following groups: 1 and 2; 1 and 3; 1 and 4; 1
      and 6; and 3 and 6. Serum sFas levels did not correlate with ALT, histological
      activity or HCV-PCR positivity within group 1. Serum sFas levels appear to
      increase in advanced stages of HCV-induced liver disease, as a result of host
      related immunological factors.

PMID- 14587306
TI  - Microscopic pathology of the liver in rats fed a Fusarium graminearum-inoculated
      diet.
AB  - Fusarium graminearum is a fungus frequently isolated from cereal grains. This
      study investigates the histopathological effects of dietary F. graminearum on rat
      liver. Treatment and control group rats were fed F. graminearum-inoculated and
      non-inoculated rice, respectively. After 14 days, all rats were sacrificed, and
      their livers analysed by electron and light microscopy. Electron microscopy of
      treatment group livers identified hepatocytes with well-developed smooth
      endoplasmic reticulum, swollen mitochondria, lipid accumulation, numerous
      vesicles containing electron-lucent materials and increased lysosomes. Many
      Kupffer's cells containing apoptotic bodies were also seen. Light microscopy
      identified hepatocytes from the treatment group with: cytoplasmic and nuclear
      pleomorphism; foci of necrosis; mononuclear cell infiltration; and presence of
      apoptotic bodies. These changes were absent in control rat livers indicating that
      dietary F. graminearum causes inflammation and parenchymal damage in the rat
      liver. This is the first histopathological study showing the association between
      F. graminearum and liver damage.

PMID- 14587307
TI  - Immunohistochemical study of surgically excised choroidal neovascular membranes.
AB  - We carried out an immunohistochemical investigation of the choroidal neovascular
      membranes from 12 eyes surgically excised as a result of age-related macular
      degeneration (n = 6) or idiopathic choroidal neovascularization (n = 6).
      Immunohistochemical staining was performed with antibodies specific for basic
      transcriptional element binding protein-2, actin or smooth muscle cell 1. In all
      membranes, the endothelial cells and stromal components around the vessels were
      immunoreactive for expression of basic transcriptional element binding protein-2,
      while immunoreactive expression of actin and smooth muscle cell type 1 was found
      in the surrounding stromal cells. These results suggest that basic
      transcriptional element binding protein-2, a zinc finger transcription factor,
      may contribute to the establishment of the choroidal neovascularization observed
      in the pathogenesis of age-related macular degeneration and idiopathic choroidal
      neovascularization.

PMID- 14587308
TI  - Actin gene-targeted RT-PCR could be a useful method for evaluating in vitro
      fungicidal activity against dermatophytes.
AB  - This study examined the effects of the antifungal agents amorolfine hydrochloride
      (AMF) and bifonazole (BFZ) on actin mRNA expression determined by reverse
      transcription-polymerase chain reaction (RT-PCR) amplification, and the
      morphology of Trichophyton mentagrophytes. In AMF-treated cultures, the hyphal
      cells of T. mentagrophytes exhibited concentration- and/or time-dependent
      progressively degenerative morphological damage. Those cultures exhibiting severe
      and necrotic morphological changes (such as crushed, bent and flattened hyphal
      cells) did not express actin mRNA. In BFZ-treated cultures, similar morphological
      changes were seen in the hyphae of T. mentagrophytes, but these changes were
      milder than observed in the AMF-treated samples, and actin gene fragments were
      amplified in all of these samples. These results indicate that actin gene
      targeted RT-PCR could be a useful tool for testing the susceptibility of
      dermatophytes to antifungal agents in vitro.

PMID- 14587309
TI  - Right ventricle of patients undergoing congenital cardiac surgery differentially
      expresses haem oxygenase-1 and heat shock protein 70 genes.
AB  - Reactive oxygen species are implicated in the pathogenesis of cardiac
      hypertrophy. Haem oxygenase-1 (HO-1), the rate-limiting enzyme in haem
      catabolism, is induced by oxidative stress and confers protection against
      oxidative tissue injuries. We used Northern blotting to examine expression of HO
      1 and heat shock protein 70 (HSP70) in the hypertrophic cardiac muscle of eight
      patients (one infant and seven children) who underwent surgery for congenital
      heart disease. Levels of HO-1 and HSP70 mRNA were significantly increased in all
      specimens, but the orders of magnitude of the increases were different,
      suggesting that the genes expressing HO-1 and HSP70 are regulated separately.

PMID- 14587310
TI  - Coating analysis of implant materials used in orthopaedic surgery.
AB  - Biocompatibility of orthopaedic surgical implants with bone tissue allows
      adequate osseointegration between the bone and implant. To achieve this, implants
      are coated with biocompatible materials. The costly plasma spray procedure is
      routinely used to coat implants but uses high temperatures (over 16,000 degrees
      C), which affect the surface quality and microstructure of the implant. We
      analysed the effect of sintering temperature, time and rate on coated and
      uncoated implants using a dipping method. The effectiveness of synthetic hydrated
      calcium silicate compound as an interlayer was also investigated, using the
      dipping method and electrophoretic deposition. Sintering temperature, time and
      rate all affected the quality of the bond with the coating, but the interlayer
      bonded effectively with both implant and biocompatible coating. Electrophoretic
      deposition resulted in imperfect bonding and some irregularity on the substrate
      surface was seen. This technique may be improved by using coating particles of a
      smaller size.

PMID- 14587311
TI  - Effects of glutaraldehyde on synovial tissue.
AB  - This study investigated the effect of glutaraldehyde on the synovial tissue of
      rabbits. Four different concentrations of glutaraldehyde solution were injected
      into one knee and the contralateral glenohumeral joint of rabbits in group A to
      group D. The concentration levels used in group A and group B were 1000 ppm and
      100 ppm, respectively. For group C and group D, samples of rinsing solutions
      obtained by rinsing arthroscopic equipment with 1 l or 2 l of isotonic saline,
      respectively, after immersion in 2% glutaraldehyde were used. The contralateral
      knee and ipsilateral glenohumeral joint of the same rabbits were injected with
      saline and used as control sites. Rabbits were sacrificed after 1 day, 7 days or
      15 days and the histopathological changes in the synovial tissues were compared.
      The most dramatic inflammatory changes were observed in group A and group B. The
      histopathological changes were greater after 7 days than after 1 day or 15 days.
      Group C and group D showed no significant differences when compared with normal
      synovium. A correlation between the concentration of the glutaraldehyde solution
      and the number of inflamed joints was observed. Very few or no inflamed joints
      were seen when samples from rinsing solutions of 1 l or 2 l of saline,
      respectively, were used.

PMID- 14587312
TI  - Comparison of the haemodynamic effects of interscalene block combined with
      general anaesthesia and interscalene block alone for shoulder surgery.
AB  - Interscalene brachial plexus block (ISB) anaesthesia is widely used with or
      without general anaesthesia in patients undergoing shoulder surgery, which is
      generally done with the patient in a sitting position. This position affects
      haemodynamics, and supplementing ISB with general anaesthesia can exaggerate
      these haemodynamic changes. This study compared ISB combined with general
      anaesthesia, with ISB alone, in 29 patients undergoing elective shoulder surgery.
      Heart rate and oxygen saturation remained stable throughout the study in both
      groups. Mean arterial pressure was significantly decreased when the patient moved
      into the sitting position in those given combined anaesthesia, whereas in those
      given ISB alone mean arterial pressure did not change significantly. Neither pain
      scores nor patient satisfaction scores differed significantly between the two
      groups. All of the patients were either satisfied or entirely satisfied with
      their anaesthesia/analgesia. There were no significant differences in side
      effects and no severe complications in either group. We advocate using ISB alone
      for patients undergoing shoulder surgery, but further larger studies are needed
      to confirm the present results.

PMID- 14587313
TI  - Moxifloxacin in the treatment of acute maxillary sinusitis after first-line
      treatment failure and acute sinusitis with high risk of complications.
AB  - This multicentre, prospective study evaluated the efficacy and safety of 7-day
      oral moxifloxacin (400 mg/day) for treatment of acute maxillary sinusitis after
      first-line treatment failure (group 1), and acute sinusitis with high risk of
      complications (group 2). Two hundred and fifty-eight patients with radiologically
      confirmed acute sinusitis were enrolled by 52 investigators; 216 patients (83.7%)
      qualified for per protocol efficacy analysis (group 1, n = 175; group 2, n = 41),
      and 92 for bacteriological analysis. Samples were collected from the middle
      meatus. The clinical success rate 7-10 days post-treatment was 92.6%.
      Bacteriological success rates were 95.7% after 3-4 days of treatment, and 97.2%
      and 95.2%, in group 1 and group 2, respectively, at 7-10 days post-treatment.
      Drug-related adverse events, including abdominal pain (2.4%), nausea (2.4%) and
      diarrhoea (1.2%), were reported in 12.2% of patients. Overall, moxifloxacin
      therapy resulted in rapid bacteriological eradication, with a high rate of
      clinical success.

PMID- 14587314
TI  - Ascorbic acid enhances hypoxic ventilatory reactivity in elderly subjects.
AB  - The reducing properties of ascorbic acid in the carotid body make it a likely
      modifier of hypoxia-sensing mechanisms. This open-label study aimed to determine
      the effect of ascorbic acid on the hypoxic ventilatory response (HVR) in a
      population of elderly women, in whom both hypoxic reactivity and ascorbic acid
      levels may be deficient. We examined the HVR to progressive eucapnic hypoxia in
      18 healthy females aged 60-80 years, before and after 10 days' ascorbic acid
      supplementation, given as a sustained release preparation of 1 g twice daily.
      Respiratory variables were recorded breath by breath, and hypoxic sensitivity was
      assessed from the linear slopes of minute ventilation and mouth occlusion
      pressure plotted against oxygen saturation. We found that ascorbic acid increased
      the HVR by a mean of 44%, this effect being driven by a higher occlusion
      pressure. We conclude that augmentation of hypoxic reactivity by ascorbic acid
      may have therapeutic potential in pathologies associated with hypoxia, which
      frequently develop in old age.

PMID- 14587315
TI  - Forearm arterial vein grafting: problems and alternative solutions.
AB  - We aimed to evaluate patency rates following forearm arterial reconstruction and
      suggest improvements. Thirty-two vein grafted reconstructions (using saphenous
      and dorsal hand veins) were evaluated for patency and development of symptoms
      using clinical examination, Colour-Doppler Sonography and angiography. Overall
      patency was 59%, with no significant difference between saphenous and dorsal hand
      veins. Stasis, turbulence, decrease in blood velocity, change in flow pattern,
      stenosis in the anastomotic area or increase in compliance was detected in 10
      patent grafts, but was not associated with symptoms. Six out of 13 non-patent
      grafted patients had severe or troublesome symptoms associated with accompanying
      nerve regeneration. To improve patency, careful microsurgical techniques, 'fit
      vein' and valveless grafts should be used. Dorsal hand veins are most appropriate
      for short defects. Patency should be evaluated soon after reconstruction.

PMID- 14587316
TI  - Acute hyposmia in type 2 diabetes.
AB  - During treatment for type 2 diabetes with a diabetic diet (without medication), a
      61-year-old Japanese man suddenly developed hyposmia. The fasting plasma glucose
      was 208 mg/dl and haemoglobin A1c was 8.6%. On investigation, there were no
      indications of disease of the brain, or the nasal or paranasal sinuses. The
      intravenous olfaction test yielded no response, indicating suspected neural
      hyposmia. After 6 months, the symptoms of hyposmia improved without medication,
      and the intravenous olfaction test results were normal. This clinical course is
      very similar to that seen with diabetic neuropathy of the third and sixth cranial
      nerves. We speculate that hyposmia in this case may have been caused by diabetic
      mononeuropathy of the first cranial nerve.

PMID- 14587317
TI  - [Preliminary analysis of the characteristics of red tide areas in Changjiang
      River estuary and its adjacent sea].
AB  - A review was made on the main environmental characteristics such as currents and
      water body, diluted water and its turning direction, upwelling, front, nutrients
      and its sources and plankton community in the Changjiang River estuary and its
      adjacent sea areas which could affect the growth, migration, assembling, resting
      and competition of harmful algae to form red tides. Analyses were also conducted
      to reveal features of the red tides events recorded in this area in terms of
      time, location and causative species. Some preliminary results from recent
      cruises carried out in the investigated sea area, where red tides were frequently
      occurring, were introduced.

PMID- 14587318
TI  - [Distribution of dinoflagellate resting cysts in surface sediments from the
      Changjiang River estuary].
AB  - In order to understand the potential of algal blooms, surface sediments were
      collected from 12 stations in the Changjiang River estuary with longitude from
      122 degrees to 123.5 degrees E and latitude from 29 degrees to 32 degrees N from
      April to May 2002 to investigate the distribution of dinoflagellate resting
      cysts, 29 different cyst morphotypes representing 19 genera and 6 groups were
      identified. Among them, there were 11 autotrophic species and 18 heterotrophic
      ones. The number of species observed in each sample was low, and varied from 10
      to 21. Cyst concentrations varied from 11.7 to 587 cysts per gram dry weight.
      Cyst concentrations and species diversity were higher in offshore areas, and
      increased from the west to the east, and from the north to the south within the
      studied area. Cysts of Alexandrium distributed widely in the Changjiang River
      estuary, with the maximum concentration of 40.4 cysts per gram dry weight. Cysts
      of harmful algal bloom causative species such as Alexandrium, Gymnodinium
      catenatum, Lingulodinium polyedra, Scrippsiellla trochoidea, Polykrikos kofoidii
      and P. schwartzii were also observed in this survey.

PMID- 14587319
TI  - [Species composition and ecological distribution of planktonic diatoms in the
      Changjiang River estuary during spring].
AB  - 53 water samples were collected from 28 stations in typical regions where redtide
      frequently occurred in the Changjiang River estuary during Spring, 2002. In
      total, 80 diatom species and varieties belonging to 31 genera were identified,
      among which, genera with high species biodiversity included Coscinodiscus which
      contained 17 species and Pleurosigma which contained 8 species and varieties.
      Quantitative analysis of diatom cell density showed that Pseudo-nitzschia
      delicatissma (3.48 x 10(3) cells.L-1, 28.54%), Melosira sulcata (1.43 x 10(3)
      cells.L-1, 16.98%) and Pseudo-nitzschia pungens (0.71 x 10(3) cells.L-1, 9.85%)
      were dominant species, which occurred at almost all stations. Higher cell density
      of Pseudo-nitzschia delicatissma and Pseudo-nitzschia pungens occurred at
      stations along 123 degrees E, while that of Melosira sulcata occurred at stations
      around Changjiang River at 31-32 degrees N. The total diatom cell density ranged
      from 0.43 x 10(3)-23.3 x 10(3) cells.L-1, with average of 4.61 x 10(3) cells.L-1.
      At station DD15 located at 123 degrees E and 30.5 degrees N, the highest diatom
      cell density was found, which was 1.85 x 10(4) cells.L-1 at surface water layer,
      and 2.33 x 10(4) cells.L-1 at middle water layer (30 m) respectively.
      Horizontally, the diatom cell density showed scattered distribution, while
      vertically, it was commonly higher at surface water layer than that at middle
      water layer.

PMID- 14587320
TI  - [Mesocosm experiment on competition between two HAB species in East China Sea].
AB  - Skeletonema costatum and Prorocentrum dentatum are the two common HAB species in
      East China Sea, and Prorocentrum is more responsible for most HAB events in
      Spring since late 90's. The HAB caused by Skeletonema usually occurs from June to
      August. However, these two species will not bloom at the same time. Two mesocosm
      experiments were conducted in East China Sea in May 1998 and May 2002. In the
      experiment of May 1998, the cell number of Prorocentrum dentatum and Skeletonema
      costatum accounted for about 85% and 11% of total cell number of phytoplankton,
      respectively at the beginning of the experiment. In control mesocosm,
      Prorocentrum dentatum dominated the community during the whole experiment. In
      phosphate-enriched mesocosm, however, Skeletonema costatum showed a high
      competition capability. In May 2002, there were 4 bags in the mesocosm
      experiment. At the beginning of the experiment, the cell number of Prorocentrum
      dentatum accounted for 55-66% of the total, and that of Skeletonema costatum
      accounted for 32-42%. During the experiment, the growth of Skeletonema costatum
      was faster than that of Prorocentrum dentatum. On the 2nd day, the cell number of
      Skeletonema costatum exceeded that of Prorocentrum dentatum. It showed that under
      high nutrients conditions, Skeletonema costatum grew better than Prorocentrum
      dentatum, but under nutrients-limited conditions, Prorocentrum dentatum could
      survival better than Skeletonema costatum.

PMID- 14587321
TI  - [Distribution features of chlorophyll a and primary productivity in high
      frequency area of red tide in East China Sea during spring].
AB  - The distributions of chlorophyll a and primary productivity were determined
      during April to May 2002 in the East China Sea. The results showed that the
      average concentration of chlorophyll a was 1.086 mg.m-3 at surface layer, and
      that nano- and pico-phytoplankton (< 20 microns) dominated the phytoplankton
      biomass in this sea region during Spring (up to 64% of total chlorophyll a
      content). Ultra-phytoplankton (< 5 microns) consisted 27% of total phytoplankton
      biomass. Nutrients and feeding pressure of zooplankton affected the distribution
      of chlorophyll a and its size-fractionation. The average primary productivity was
      10.091 mg.m-3.h-1, while that of red tide tracking stations R-03, RL-01 and RG-01
      was 399.984 mg.m-3.h-1. Light and nutrients were the main factors affecting the
      distributions of chlorophyll a and primary productivity. The station DC-11 had a
      high concentration of phytoplankton biomass. The surface layer concentration of
      chlorophyll a and primary productivity were up to 9,082 mg.m-3 and 128,79 mg.m
      3.h-1, respectively, but the color of the seawater was normal.

PMID- 14587323
TI  - [Ecological characteristics of Prorocentrum dentatum and the cause of harmful
      algal bloom formation in China Sea].
AB  - Large-scale harmful alga bloom (HAB) has been found in Changjiang River estuary
      and Zhoushan archipelago in recent three years, and the alga is Prorocentrum
      dentatum, which distributes in the sea areas with high salinity and (may)
      originates in outer sea area. Data from recent HAB rapid monitoring and
      ecological investigation were analyzed to study its ecological characteristics
      and forming inducement. The results showed that the most suitable temperature and
      salinity range for HAB forming was from 18 degrees C to 22 degrees C and from 21
      to 31, respectively. The P. dentatum was motile and owned diurnal vertical
      migration bringing them the advantages in obtaining light and nutrients.
      Eutrophication was the preliminary condition, and water temperature, nitrate
      content, upwelling current, and strong competence on low phosphate environment
      were important to cause and maintain HAB.

PMID- 14587322
TI  - [Redescription of Prorocentrum donghaiense Lu and comparison with relevant
      Prorocentrum species].
AB  - In this paper, the detailed morphology of Prorocentrum donghaiense was studied.
      Taxonomic comparison was made between P. donghaiense and other relevant
      Prorocentrum species. The results suggested that distinct differences existed
      among them with respect to their conservative characteristics of morphology and
      cell sizes. This kind of discrepancy was far beyond that of individual variations
      within same species due to environmental factors. Therefore, the high biomass
      bloom-forming species in the East China Sea was not real Prorocentrum "dentatum"
      Stein, but P. donghaiense Lu that was re-described in the present paper. P.
      donghaiense appeared in the East China Sea, and P. "dentatum" occurred in
      Japanese and Korean waters should be the same species.

PMID- 14587324
TI  - [Scanning electron-microscopic study on Prorocentrum dentatum from the East China
      Sea].
AB  - There is an argument whether the bloom causative species of the East China Sea is
      Prorocentrum dentatum or a new species. Based on the scanning electron
      microscopic study, we compared the detailed surface structure of the sample from
      the East China Sea and Prorocentrum dentatum strain (CCMP1517) from the Provasoli
      Guillard National Center for Culture of Marine Phytoplankton, USA. The results
      showed that these two samples belonged to one species. After reviewing
      literatures, it can concluded that the bloom causative species of the East China
      Sea is Prorocentrum dentatum, rather than a new species.

PMID- 14587325
TI  - [Microzooplankton herbivory during red tide-frequent-occurrence period in spring
      in the East China Sea].
AB  - Five typical stations in the Changjiang River estuary and adjacent waters of the
      East China Sea, were chosen as the sites to study phytoplankton growth and
      microzooplankton ingestion by on-deck-incubation dilution experiment from 25th
      April to 25th May 2002. The results showed that microzooplankton ingestion was a
      key process for controlling red tide event. Strombidium sulcatum, Noctiluca
      scintillans and Mesodinium robudium were dominant microzooplankton species. In
      this study, the ingestion rate of microzooplankton ranged from 0.28 to 1.13 d-1;
      ingestion pressure on percentage of phytoplankton standing crop ranged from
      35.14% to 811.69%; ingestion pressure on percentage of potential production
      ranged from 74.04% to 203.25%; and ingestion rate of phytoplankton carbon ranged
      from 9.58 to 97.91 C.L-1.d-1. The microzooplankton grazing rate, ingestion
      pressure on percentage of phytoplankton standing crop, and ingestion rate of
      phytoplankton carbon were higher near coastal area, but lower at open sea, and
      the microzooplankton ingestion pressure on percentage of phytoplankton potential
      production was no the contrary. Compared with the similar studies around the
      world, the ingestion pressure of microzooplankton in the East China Sea was at a
      higher level. The primary deduction was that Strombidium was the key
      microzooplankton species on controlling Prorocentrum dentatum, the most important
      red tide species in the East China Sea.

PMID- 14587326
TI  - [Ecological characteristics of zooplankton in frequent HAB areas of the East
      China Sea in spring].
AB  - A comprehensive oceanographic survey was made in the East China Sea (122 degrees
      123 degrees 30'E, 29 degrees-32 degrees N) during April to May, 2002, and the
      zooplankton samples were collected by zooplankton net (mesh size 0.567 mm).
      Analyses on the ecological characteristics of zooplankton such as its quantity,
      community characteristics, species composition and dominant species showed that
      128 species of diet zooplankton were identified (16 pelagic larvae and fish
      juveniles were not involved). Among them, copepods occupied dominant position,
      including 40 species, composing 31.25% of diet zooplankton. The community was
      divided into 3 ecological types, in which, eurythermy and euryhalinity occupied
      dominant position. Key species, Calanus sinicus, was the first dominant species
      (142.10 ind.m-3, composing 68.09% of diet zooplankton abundance). The average
      biomass of zooplankton was 243.80 mg.m-3 (55.53-773.92 mg.m-3), and the highest
      density (> 500 mg.m-3) was found in the estuary area of the Yangtze River (30
      degrees 45'-31 degrees 15'N, 122 degrees 45'-123 degrees 15'E). The average
      biomass of diet zooplankton was 195.96 mg.m-3 (55.53-496.09 mg.m-3). It was also
      showed that the biomass value of the estuary area of the Yangtze River (the north
      of 30 degrees 30'N) was higher than that of the southwest of Zhoushan waters, and
      that of the offshore of the estuary area of the Yangtze River (122 degrees 45'E)
      was higher than that of coastal waters. The mean value of diversity index (H')
      was 2.12 (1.09-3.73), and the stations having low H' (< 2) occupied 37.03%. The
      index of diversity, evenness and richness in the estuary area of the Yangtze
      River were low, but dominance was high. These results showed that the community
      structure of zooplankton in studied areas was not stable. Regression analysis
      results showed that main factors in relation to the characteristic distribution
      of zooplankton were temperature, diatom abundance, and dinoflagellate abundance.

PMID- 14587327
TI  - [Nutrient distribution and its controlling mechanism in the adjacent area of
      Changjiang River estuary].
AB  - In this paper, the nutrient distribution, its structural characteristic and
      controlling mechanism around the Changjiang River estuary during Autumn 1997 and
      Spring 1998 were discussed, and a clear seasonal variation of nutrient
      distribution and structure was observed in this area. The concentrations of NO3(
      )-N, SiO3(2-)-Si, PO4(3-)-P, DOP, PP and TP in Autumn 1997 were higher than those
      in Spring 1998, and their average concentrations were 4.97, 11.6, 0.44, 0.26,
      0.82 and 1.52 mumol.L-1, respectively. However, the concentrations of NO2(-)-N,
      NH4(+)-N, DON, PN and TN in Spring 1998 were higher than those in Autumn 1997,
      with the average concentration of 0.70, 2.26, 9.88, 7.88 and 25.3 mumol.L-1,
      respectively. The main form of phosphorus in Autumn 1997 was PP, with the
      percentage about 54%, while PO4(3-)-P was the dominant fraction, with about 51%
      of phosphorus in Spring 1998. Both DON and PN were the main fractions of nitrogen
      in Autumn 1997 and Spring 1998 as well. Due to the influences of the Changjiang
      dilution water, the concentrations of phosphate, nitrate and silicate along the
      coastal area were higher than those in the outer area, except the phosphate in
      Spring 1998, which mainly came from Taiwan warm current. It indicated that the
      distribution of the nutrients in the survey area was mainly controlled by the
      Changjiang dilution water and the high salinity sea-water from the Taiwan warm
      current, and the influence of Taiwan warm current on phosphate was larger in
      Spring than in Autumn.

PMID- 14587328
TI  - [Distributions of COD and petroleum hydrocarbons and their relationships with
      occurrence of red tide in East China Sea].
AB  - Based on the data of COD and petroleum hydrocarbons collected in the cruise from
      April 25 to May 2, 2002 in intensive red tide occurrence areas in East China Sea,
      the distribution of COD, and petroleum hydrocarbons and the eutrophication
      index(EI) were analyzed. The results showed that the EI and COD value were both
      high in coastal water, and decreased gradually away from shore. After the
      preliminary study on the relationships between correlative factors and occurrence
      of red tide, it was found that high EI and COD were necessary. There would be
      great chances for the red tide to break out under conditions that the EI was
      between 2.5 and 15 and COD concentration was between 0.8 to 1.4 mg.L-1 in
      seawater, along with the favorable temperature and salinity.

PMID- 14587329
TI  - [Nutrient distribution and its relationship with occurrence of red tide in
      coastal area of East China Sea].
AB  - Nutrient (NO3(-)-N, PO4(3-)-P, Sio3(2-)-Si, NH4(+)-N, etc.) concentrations in
      coastal area of East China Sea were measured during April 25 to May 2, 2002, and
      the relationship between the spatial distribution of the nutrients and the red
      tide occurrence in the studied area was analyzed. The results showed that
      compared to the 1st class seawater quality of the national standard, the
      concentrations of dissolved inorganic nitrogen (DIN) and PO4(-)-P were 46% and
      60% higher, respectively, showing that the studied area, especially the
      Changjiang River estuary and the Hangzhou Bay, was at a disadvantage of
      eutrophication. Furthermore, the nutrient concentrations inshore were much higher
      than those offshore, and the isolines nearly paralleled with the coastline,
      meaning that the nutrient distributions were mainly influenced by terrestrial
      discharges. It also showed that the relatively high concentrations of nutrients,
      especially DIN and PO4(3-)-P, might result in the red-tide occurrence. However,
      the red tide did not occur in the area with the highest concentrations of the
      nutrients, further demonstrating that the eutrophication was not the unique
      environmental factor inducing red-tide occurrence.

PMID- 14587330
TI  - [Sediment chlorophyll in HAB (harmful Algal bloom) area of East China Sea].
AB  - The content and distribution of chlorophyll a (chl-a) and phaeopigments (pha-a)
      in the sediment of East China Sea was investigated in August and September, 2002.
      The results showed that chlorophyll a and phaeopigments had the same resource.
      Both chlorophyll a and phaeopigments decreased significantly with increasing
      depth, and would be stable to a certain depth. There are several observed leaps
      in the vertical distribution of chlorophyll a and phaeopigments, which might
      reflect the effects of bioturbation. The chlorophyll a and phaeopigments
      concentration on the surface of sediment varied from 0.14 to 1.17 micrograms.g-1
      and 0.83 to 5.58 micrograms.g-1, respectively, and the mean concentrations in the
      top centimeter of sediment (0-0.5 cm) were 0.54 microgram.g-1 for chlorophyll a
      and 2. 45 micrograms.g-1 for phaeopigments. The spatial distribution of benthic
      chlorophyll a and phaeopigments were affected by the combination of several
      factors such as depth (and therefore light), temperature, salinity and water
      content. As the main degradation product of chlorophyll a, phaeopigments became
      the main type of chlorophyll while increased to certain extent, and accounting
      for 80-90% of total chlorophyll. Due to the water temperature, the surface
      chlorophyll a and phaeopigments concentration varied significantly with the
      season. Total chlorophyll a in the sediment accounted for 31% of total
      chlorophyll a in the water column.

PMID- 14587331
TI  - [Nutrient elements in the atmospheric wet deposition in Changjiang River
      estuary].
AB  - In order to study the effects of atmospheric wet deposition on red tide, five
      kinds of nutrient elements were measured with 64 rainwater samples collected at
      Shengsi Archipelago from May 2000 to April 2001. The results showed that there
      were obvious differences between monthly average concentrations, due to the
      different resource and precipitation. The variation of seasonal fluxes suggested
      that the wet deposition might cause red tide except in winter. The annual
      concentrations of NO3-N, NH4(+)-N, NO2(-)-N, PO4(3-)-P and SiO3(2-)-Si were
      20.23, 30.14, 0.11, 0.045 and 3.43 mumol.L-1, respectively, and their annual
      fluxes were 2.67 x 10(8), 3.98 x 10(8), 0.014 x 10(8), 0.0059 x 10(8) and 0.45 x
      10(8) mol, respectively. Compared with river input, they were much more smaller.

PMID- 14587332
TI  - [Nutrients regeneration speed of sediment in harmful algae blooms (HAB) area of
      East China Sea].
AB  - The fluxes of dissolved nutrients at sediment-water interface were investigated
      at 4 stations in the HAB area of East China Sea in May 2001 and May 2002. The
      benthic fluxes of nutrients were determined by incubating the sediment core
      samples with bottom seawater bubbled with air or nitrogen. The transfer of
      nutrients was more active under anoxic condition. The fluxes of dissolved
      nutrients were generally high at the stations close to the coast. The sediment
      was the source of SiO3(2-), which accounted for 6% of primary production. For DIN
      and PO4(3-), the sediment was the sink. DIN and PO4(3-) adsorbed by sediment
      accounted for 5.9% and 67% of the riverine DIN and PO4(3-) inputs, respectively,
      and the inputs of SiO3(2-) accounted for 7.8%.

PMID- 14587333
TI  - [Effects of terrestrial input on the harmful algal bloom area--with aluminum as
      an example].
AB  - In recent years, eutrophication and frequently occurred harmful algal blooms
      (HAB) become serious in the coastal area near Changjiang River estuary, and the
      nutrients came from Changjiang River may be the main sources for them. Aluminum
      could be used as a useful tracer for the terrestrial input and the movement of
      different water mass, since it enters into the natural water with the erosion
      products of soil and rock, and its residence time in the ocean is short and
      uneasy to be disturbed by the activities of human being. Based on our results,
      the concentration of dissolved Al was higher in Autumn than in Summer, and showed
      some relationships with the salinity and suspended particulate matter (SPM). The
      concentration of Al in the HAB area was higher than 0.04 mumol.L-1, which showed
      the significant influence from the terrestrial input. The concentration of
      dissolved Al decreased nearly 40% after the occurrence of HAB, and the
      flocculation of dissolved Al and its absorption onto the surfaces of biogenic
      particles might be the main reasons. There still need further study about the
      variation of Al forms and its mechanism during the occurrence of HAB.

PMID- 14587334
TI  - [Nutrient distributions and their limitation on phytoplankton in the Yellow Sea
      and the East China Sea].
AB  - Based on field observations during 1997 to 1999, the distributions of
      micronutrients and their limitation on the growth of phytoplankton in the Yellow
      Sea and the East China Sea were discussed in this paper. The results showed that
      there were abundant nutrients in the area of the east and northern-east of the
      Changjiang River estuary, and the nutrients came from the extension of the
      Changjiang River diluted water and the transportation of the Subei Coastal water.
      Besides, the maximum extension range of the nutrients in the Changjiang River
      diluted water was observed during the catastrophic flooding period of the
      Changjiang River in the summer of 1998. Based on the Redfield ratio (Si:N:P =
      16:16:1) in which, three essential nutrients were utilized by marine
      phytoplankton, the Si/N/P ratios were calculated and studied for the upper water
      of the Yellow Sea and the East China Sea. The results indicated that Si/N ratios
      were very high, which suggested that silicate was not the limiting factor for the
      growth of phytoplankton in the Yellow Sea and the East China Sea. However, under
      the influence of terrestrial runoff, especially the Changjiang River runoff which
      was rich in combined nitrogen and had very high N/P ratios, high N/P ratios
      occurred in the Changjiang River estuary and its adjacent areas such as the south
      and southwest of the Yellow Sea, the inshore area of the East China Sea and the
      area east of the Changjiang River estuary in spring and summer. As a result, in
      contrast to general open marine systems, the systems in these areas resembled
      estuarine ones rather than typical marine ones. The primary production in a
      considerable portion of the Yellow Sea and the East China Sea might be limited by
      phosphate rather than nitrogen.

PMID- 14587335
TI  - [Temporal dynamics of phytoplankton and nutrients during red tides].
AB  - The relationships between temporal dynamics of phytoplankton density and
      nutrients (NO3-, NH4+, PO4(3-), SiO3(2-), Fe) contents in the water body at Aotou
      waters of Daya Bay during red tide were comprehensively analysed based on the
      fixed position investigation of red tide in the summer of 2000 and the several
      years investigation data by using grey linear regression model. The relationships
      between phytoplankton cell density and chlorophyll a content were also analysed.
      The results showed that the predicted values were well consistent with the
      measurement values, and their correlation coefficients were between 0.51-0.83.
      Red tide might break out if chlorophyll a contents in water body were larger than
      5.8 micrograms.dm-3. The study could provide a simple effective method to
      forecast red tide by sampling water samples to analyse chlorophyll a
      concentration, or using SeaWiFS data, and then, to calculating phytoplankton
      density. In addition, the primary productivity of the water areas was controlled
      by phosphorus.

PMID- 14587336
TI  - [Hydrologic distribution characteristics of HAB frequent occurrence area in the
      outer Changjiant River estuary].
AB  - Based on survey data, this paper analysed the hydrologic characteristics of HAB
      frequent occurrence area in the outer Changjiang River estuary. The results
      showed that this area is an area in which the plume front with a salinity of 17
      30 in the outer Changjang River estuary, the divergent surface current of the
      plume front and the upwelling of the high salinity Taiwan bottom warm current are
      coexisted. In Spring and Summer, the diluted Changjiang River water of this area
      changed its flow direction under the effect of southwest-northeastward current,
      possibly due to the large runoff from the Changjiang River to the sea. The
      upwelling usually occurred at the west side slope between the first turning point
      and the deep slot top of the outer Changjiang River estuary. This turning point
      was on the north side in Spring and on the south side in Summer, but in Autumn,
      no turning point was existed, possibly due to the small runoff. The distribution
      characteristics of residual current in Spring and Summer was that the adjacent
      area of plume front was the convergent area of surface and bottom currents, the
      surface residual current in the upwelling area was at divergent, and the bottom
      residual current had the characteristics of converging toward the Changjiang
      River estuary along the deep slot.

PMID- 14587337
TI  - [Distribution of phytoplankton and water dynamical environmental factors in high
      red tide occurrence area of Changjiang River estuary].
AB  - Species composition and cell abundance of phytoplankton, and its relations with
      environmental factors were investigated in the Changjiang River estuary of east
      China sea (30 degrees 50'-31 degrees 50'N, 121 degrees 50'-123 degrees 00'E). A
      total of 110 taxa belonging to 45 genera of phytoplankton in the investigation
      area were identified. The main species of phytoplankton resulted in red tide were
      Skeletonema costatum and Prorocentrum dentatum, etc. Phytoplankton abundance in
      the day was higher than that at night. The vertical distribution of phytoplankton
      in different water bodies was not obvious. The ecological groups of phytoplankton
      were freshwater group, estuarine and brackish water and low salinity group in the
      coast, high salinity and warm water group in off-sea, and widely ranging group.
      The abundance of phytoplankton in the Changjiang River estuary was 1.6 x 10(3)
      75.2 x 10(3) ind.dm-3. The species composition and cell abundance of
      phytoplankton were related to the freshwater pouring into the Changjiang River
      estuary. The three waters in the area affecting the distribution of phytoplankton
      were the Changjiang River estuary water, freshwater, and warm water from outsea.

PMID- 14587338
TI  - [Response of Prorocentrum minimum growth to zinc limitation].
AB  - Studies on the growth and physiological response of red tide alga Prorocentrum
      minimum to three Zn2+ levels were showed that the specific growth rate and
      biomass were limited in low Zn(2+)-grown cells (1.4 pmol.L-1, which were 0.40 d-1
      and 51,100 cell.ml-1 respectively. The specific growth rate was not significantly
      different when the Zn2+ concentration in medium was increased over 24.4 pmol.L-1,
      but there was a slight decrease in biomass; however, both specific growth rate
      and biomass were much higher than those in low Zn(2+)-grown cells. It was also
      showed that chlorophyll a synthesis was limited due to Zn2+ deficient, and
      therefore, the cells became light saturated at higher irradiance under Zn-limited
      condition. Light-saturated photosynthetic rates (Pm) and photosynthetic
      efficiency (alpha) increased significantly with increasing Zn2+ concentrations.
      It was concluded that Zn2+ concentration might be one of the key factors
      affecting red tide blooms in eutrophication environment.

PMID- 14587339
TI  - [Nitrogen and phosphorus absorption and growth characteristics of Alexandrium
      tamarense].
AB  - The uptake of nitrate and phosphate by Alexandrium tamarense and its growth
      characteristics were studied in laboratory cultures, which were conducted using
      environmentally realistic levels of physical factors during red tide occurrences.
      The results indicated that the specific growth rate had little difference under
      three nitrate levels (low-nitrate, 0.0882 mmol.L-1; middle-nitrate, 0.882 mmol.L
      1; high-nitrate, 2.646 mmol.L-1). The cell yield was the lowest at low-nitrate, a
      maximum yield was achieved at the middle-nitrate, which increased by 44.7% and
      53.6% respectively, compared with high-nitrate and low-nitrate. The cell yield
      increased with increasing phosphate concentrations in cultures (low-phosphate,
      0.0036 mmol.L-1; middle-phosphate, 0.036 mmol.L-1; high-phosphate, 0.108 mmol.L
      1), and the maximum yield (17200 cell.ml-1) was observed at high-phosphate
      concentration, while the maximum specific growth rate occurred at middle
      phosphate. The growth conditions had a significant effect on the uptake rate of
      nitrate and phosphate by cells, and the cells grown in low-nitrate and low
      phosphate cultures had a higher uptake rate. Further experiment suggested that
      lower ratio of N/P promoted the propagation of cells, and the supplementation of
      nitrate at later exponential growth phase had a positive effect to the
      accumulation of biomass.

PMID- 14587340
TI  - [Distribution and germination of Alexandrium sp. cysts in coastal areas of
      Southeast China Sea].
AB  - Studies on the distribution and germination of Alexandrium sp. (A. tamarense + A.
      catenella) cysts in coastal areas of Southeast China showed that the cysts were
      only found at X1 and X2 of Xiamen Harbor, whose density was quite low (0.4 ind.g
      1). In Guangxi, the cysts were found at G2 station, with a density of 2.5 ind.g
      1. There were cysts at three stations at Minjiang River estuary. The density
      reaches maximum value at 4-6 cm sediment of M4 station, up to 6 ind.g-1. In
      Changjiang River estuary, the cysts distributed widely and had the largest
      density, up to 23.2 ind.g-1 at 8-10 cm sediment of DG-26 station. The
      distribution of Alexandrium sp.cysts was relevant to sediment type, sedimentation
      rate and current. Light had no effect on germination. With increasing
      temperature, germination and survival rates also increased, while the germination
      time decreased. Anoxia (0.01 mg O2.L-1) inhibited germination completely.
      Alexandrium sp. cysts could germinate throughout the year under favorable
      conditions.

PMID- 14587341
TI  - [Effects of Alexandrium tamarense and Prorocentrum donghaiense on rotifer
      Brachionus plicatilis population].
AB  - The effects of Prorocentrum donghaiense and Alexandrium sp., causative species of
      harmful algal bloom of East China Sea in May 2002, on rotifer Brachionus
      plicatilis population were studied in the laboratory. The results showed that
      Alexandrium tamarense (ATHK) had a lethal effect on B. plicatilis and the 48hLC50
      was about 1300 cell.ml-1. The toxin comparison of different fractions showed that
      the algal culture and re-suspended algal cells had the adverse effects, and the
      alga at earlier growth phases showed a stronger impact, indicating that the
      inhibitory effect was related with the activity of the living algal cells. P.
      donghaiense at high densities (4 x 10(4), 5 x 10(4) and 10 x 10(4) cell.ml-1) had
      an adverse effect on B. plicatilis population, while at low densities (1 x 10(4),
      2 x 10(4) and 3 x 10(4) cell.ml-1), the alga could be used as food for rotifer
      population. When the two algae were mixed, the lethal effect of A. tamarense
      could be decreased by P. donghaiense. The results indicated that the above HAB
      event could affect the micro-zooplankton population in the occurrence area of
      East China Sea.

PMID- 14587342
TI  - [Paralytic shellfish toxins in shellfish from the coast of high frequent harmful
      algae blooms occurrence areas in East China Sea and South China Sea].
AB  - The paralytic shellfish poisoning (PSP) toxicity levels of shellfish collected
      from shellfish growing zones in Zhoushan areas of East China Sea and Shenzhen
      areas of South China Sea during January-November 2002 were determined with AOAC
      bioassay method. The results showed that the toxicity levels of shellfish from
      Zhoushan were very low, and few shellfish samples could be detected the PSP
      toxicities. The same levels appeared in the shellfish from Shenzhen, but the
      percentage of shellfish samples contaminated PSP was up to 30%, and the scallop
      Chalmys nobilis was dominated in the contaminated shellfish species. Analyses on
      the toxic profiles of digest gland and edible tissue extraction of scallop from
      Shenzhen showed that a similar suite of toxins presented in the gland and edible
      tissues. The high potency neoSTX and low potency GTX5 had a high proportions, up
      to 60.8% and 11.4%, respectively in the tissue, and the high potency GTX1 + 2 and
      GTX5 were the dominant toxins, up to 38.9% and 20%, respectively in the gland.
      Most of the toxin were accumulated in ingested gland of scallop, and the toxic
      content in gland was about 8 folds more than that in the edible tissues.

PMID- 14587343
TI  - [Effects of marine bacteria on the growth and toxin production of red-tide algae
      under different pH and salinities].
AB  - The effects of strain S10 isolated from sediments of Xiamen Western Sea Area on
      the growth and paralytic shellfish poison (PSP) production of Alexandrium
      tamarense at different pH and salinities were studied. The results showed that
      the alga grew well at pH 6-8 and at salinity of 20-34. The toxicity of A.
      tamarense varied markedly at different pH and salinities: it decreased with
      increasing pH, while increased with salinity and reached its peak value at the
      salinity of 30, and then declined. The strain S10 inhibited the growth and the
      PSP production of A. tamarense at different pH and salinities. It had the best
      inhibitory function on the growth of A. tamarense at pH 7 and salinity of 34. The
      best inhibitory function on the PSP production of A. tamarense was at pH 7, but
      this inhibitory function was not related to salinity.

PMID- 14587344
TI  - [Removal of different species of red tide organisms with an effective clay
      complex system].
AB  - An effective clay-complex system was composed on the base of clay by added other
      two components A and B. Different red tide species, such as Scrippsiella
      trochoidea, Amphidinium carterae and Heterosigma akashiwo, were coagulated by
      this clay-complex system, and the optimum conditions for removal red tide
      organisms were obtained by means of orthogonal test. The results showed that clay
      was the most important factors in this complex system to coagulate these three
      organisms. The removal efficiency on three species was in order of Scrippsiella
      trochoidea > Amphidinium carterae > Heterosigma akashiwo. At the same time, a
      preliminary study of mortality rate on Penaeus japonicus (length between 1.0 to
      1.5 cm) was conducted with this system, and the result of toxic test revealed
      that the mortality of aquaculture shrimp in control group (nothing added) reached
      to 80% after 96 h, however, while that of other three groups which added clay and
      other two components A and B, was below 40%. Thus, it implied that the addition
      of clay would be harmless to Penaeus japonicas. Furthermore, suitable
      concentration of components A and B was not harmful for the aquaculture shrimp,
      but increased the removal efficiency of red tide organisms. The preliminary
      results showed that this clay-complex system would be available in the removal of
      red tide organisms in filed.

PMID- 14587345
TI  - [Extinguishment of harmful algae by organo-clay].
AB  - Periodic and widespread algal blooms have caused a variety of problems for
      aquatic life and human activity throughout the world. Currently, the only
      remedial practice employed for removing algal blooms is to spread clay on the
      surface of the water. But, the algal removal efficiency by the crude minerals are
      not really ideal, and how to improve the capability of clays to remove algae is
      now the technological focus, which also is fatal to the practical value of clays.
      In this study, hexadecyltrimethyleamine bromide (HDTMAB), one kind of cationic
      organo-surfactants, was chosen to improve kaolin by surface sorption and cationic
      exchange, and was tested to remove Prorocentrum donghaiense, a red tide organism
      in Donghai Sea. The results indicated that organo-clay had an excellent ability
      to extinguish red tide organisms, even under the application of 0.01 g.L-1, and
      could subside more than 95% red tide organisms in 24 h. The efficient algae
      removal by organo-clay might be from the reversal of the surface electric charge
      on clay particles, the "net capture" by the long lipoid chains of HDTMAB, and the
      local high density of HDTMAB on particles surface, which could effectively kill
      algal cells.

PMID- 14587346
TI  - [Inhibition and elimination of chlorine dioxide on Phaeocystis globosa].
AB  - Different densities of red tide organism, Phaeocystis globosa (ST strain) were
      exposed to different concentrations of chlorine dioxide. The results showed that
      chlorine dioxide could effectively kill and control the algae. When the algae, in
      the density of 2.35 x 10(9) cells.L-1, was exposured to ClO2 above 0.74 x 10(-2)
      mmol.L-1, it was inhibited, and eliminated under ClO2 concentration above 2.96 x
      10(-2) mmol.L-1. When the density of algae was 2.35 x 10(9), 1.18 x 10(9), 4.70 x
      10(8) and 1.18 x 10(8) cells.L-1, the concentration of chlorine dioxide which
      could kill the algae efficiently in 96 h was 2.96 x 10-2, 2.22 x 10-2, 1.48 x 10
      2 and 0.59 x 10-2 mmol.L-1, respectively. Under the same rate of inhibition or
      elimination, the higher the density of algae was, the lower the concentration of
      chlorine dioxide was to effectively control the growth of algae cell, ClO2 could
      be considered as a potential algaecide to control red tide.

PMID- 14587347
TI  - [Povidone-iodine and isothiozolone for removing red tide algae Phaeoecystis
      globosa].
AB  - Studies on the removal and control of red tide algae Phaeoecystis globosa by
      povidone-iodine and isothiozolone algaecide showed that Phaeoecystis globosa
      could be killed and controlled by povidone-iodine and isothiozolone. The
      effective concentration of povidone-iodine was 30 mg.L-1, and that of
      isothiozolone was 0.30 mg.L-1. Using povidone-iodine and isothiozolone together
      could improve the effect, and the ideal composite ratio of povidone-iodine and
      isothiozolone was 1.0:0.15.

PMID- 14587348
TI  - [Spectroscopic properties of Heterosigma akashiwo under iron limitation].
AB  - Room-temperature absorption spectra of H. akashiwo cells under iron limitation
      showed a chlorophyll c absorption peak at 630 nm, 2 nm blue-shifted from its
      normal position of 632 nm. Moreover, because of the increase in the relative
      carotenoid abundance compared to Chl a, there was an extra shoulder peak at 480
      nm for the iron-limited cells. Their fluorescence spectra (77 K) have one
      prominent chlorophyll emission peak at 685 nm. By comparison with Fe-replete
      cells (10 mumol.L-1), the fluorescence yield from 685 nm band increased by about
      2 times in Fe deplete cells (5 nmol.L-1), and about 1.4 times in low iron cells
      (100 nmol.L-1), respectively. 48 h after Fe addition, the height of 685 nm peak
      was considerably decreased from that observed in low iron (100 nmol.L-1) and iron
      deficient (ID) cells before Fe addition, which indicated that there was a
      significantly higher energy dissipation, and thus, a less effective
      photosynthesis under the lack of Fe.

PMID- 14587349
TI  - [Induction of biochemical composition in Heterosigma akashiwo under Fe stress].
AB  - The iron-stress mediated effects on biochemical constituents of red tide alga H.
      akashiwo were examined in Fe-replete and iron deficiency, and low iron batch
      cultures. The content of all pigments decreased under iron limitation, and the
      cellular chlorophyll a concentration decreased by more than 2-fold compared to
      that under iron replete condition. This change in Chl a was accompanied by a
      corresponding decrease in Chl c per cell, resulting in no trend in the ratio of
      Chl c to Chl a. The cellular carotenoids content decreased by more than 1.5-fold
      compared to that under iron replete condition. As a consequence,
      carotenoids/chlorophyll a ratio increased in Fe-deficient cells. Carbohydrate
      content was reduced under iron stress, and total proteins decreased with the
      decrease of iron concentration. A crude fractionation of the soluble proteins
      demonstrated that 17 kD and 55 kDa proteins in soluble fraction were induced.

PMID- 14587350
TI  - [What the Prorocentrum species should be?--a review on identification of a
      Prorocentrum species from the East China Sea].
AB  - In the past decade, the Prorocentrum bloom was the most frequently occurred bloom
      in the East China Sea. It occurred every one year or two years, and covered huge
      areas. There were arguments on the identification of Prorocentrum bloom causative
      species. Some scientists thought the species being P. dentatum Stein, but the
      others thought that it was a new species, P. donghaiense Lu. For achieving the
      proper classification of the species, an "International Workshop on HAB Causative
      Species--Taxonomic View on a species of Prorocentrum in the East China Sea" was
      held in Shenzhen, China in November, 2002. By reviewing as much as available
      references, and by comparing the Prorocentrum specimen from the East China Sea
      with those from Japan, Korea and USA, scientists participated in this Workshop
      agreed that: 1) the specimens from Japanese and Korean waters, and from CCMP, USA
      were the same species; 2) the features of anterior projection and cell surface
      marking were similar to those of originally described P. dentatum Stein; 3) the
      major difference is the cell size. The specimens from the East China Sea were
      mostly less than 20 microns long, whereas the size of the original described P.
      deatatum was larger than 50 microns; 4) the minor difference is the shape of the
      cell end. The original described P. deatatum was with a pointed end, whereas the
      cells from the East China Sea were mostly with a rounded end. There was no final
      agreement for the species identification at the Workshop. By summing all views of
      scientists from the Workshop, the authors suggested that the bloom causative
      species of Prorocentrum in the East China Sea, as well as so-called species of P.
      dentatum from other East Asian waters, should be the same species. They are all
      P. donghaiense Lu.

PMID- 14587351
TI  - [Research advance in effects of harmful algal bloom species on zooplankton].
AB  - The research on the effects of harmful algal bloom (HAB) algae on zooplankton has
      been drawn more and more attention. This paper summarized the adverse effects of
      HAB algae on zooplankton, which included reduced survival, inhibited growth,
      reduced fecundity of female, fertilization failure of eggs or hatching failure of
      zygote, inhibited embryo development, naupliar abnormal development or
      abnormality, inhibited grazing and changed behavior of zooplankton, etc. The main
      intoxication ways included decreased utilization of food, physiology impairment,
      damaged cell membrane, reduced gamete quality, and inhibited mitotic and embryo
      development by phycotoxins or exudations released by algae. Additionally, the
      lack of full nutrition, especially of polyunsaturated fatty acids in some algal
      species cells could also affect zooplankton growth and reproduction.

PMID- 14587352
TI  - [Advances in researches of aquatic ectoenzyme and its relationship with red
      tide].
AB  - Ectoenzymes play an important role in the material cycle and energy conversion in
      aquatic ecosystem. The researches of ectoenzyme are of significance in further
      understanding the marine carbon biogeochemical cycle and the countermeasures of
      algae under bloom conditions. In this paper, the research methods, characteristic
      activity and size distribution, controlling factors and their ecological
      significances of algal ectoenzymes were reviewed, and ectoenzyme introduced as
      one kind of new trophic state index.

PMID- 14587353
TI  - [Algorithms of multiband remote sensing for coastal red tide waters].
AB  - The spectral characteristics of the coastal waters in East China Sea was studied
      using in situ measurements, and the multiband algorithms of remote sensing for
      bloom waters was discussed and developed. Examples of red tide detection using
      the algorithms in the East China Sea were presented. The results showed that the
      algorithms could provide information about the location and the area coverage of
      the red tide events.

PMID- 14587354
TI  - [Spectrophotometer detection of benzalkonium bromide concentration in seawater].
AB  - Benzalkonium bromide is a high-efficiency algaecide. Its concentration in
      seawater was measured by the method of spectrophotometer. The results indicated
      that the deposition appeared if the concentration of benzalkonium bromide in
      seawater was more than 50 mg.L-1, and affected the detection of benzalkonium
      bromide. But, there was a good linear relationship between concentration and
      absorbance when the concentration was lower than 50 mg.L-1 (R2 = 0.9996).
      Therefore, spectrophotometer could be used to detect benzalkonium bromide in
      seawater.

PMID- 14587355
TI  - Tobacco smoking: current concepts in etiology and treatment.
AB  - Tobacco smoking is the most important preventable cause of death and disease.
      Despite an increased awareness of the addictive nature of smoking and
      availability of effective treatments, smoking continues to be widespread among
      individuals with psychiatric disorders. Moreover, mental health professionals
      remain reluctant to address smoking among their patients for a variety of
      reasons. Recent research has provided a wealth of data that have shaped the
      concept of tobacco smoking as a chronic addictive disorder and also demonstrated
      the efficacy of smoking cessation interventions. This paper reviews the important
      factors that contribute to smoking and the various pharmacological and
      psychosocial interventions for smoking cessation from a biopsychosocial
      perspective. It also makes recommendations for the rational use of these
      interventions to treat nicotine dependence in individuals with psychiatric
      disorders.

PMID- 14587356
TI  - The tobacco use crisis and mental health.

PMID- 14587357
TI  - Hamlet as process: a novel approach to using literature in teaching psychiatry.
AB  - Psychiatrists have made many forays into literature for the purposes of theory
      building, clinical understanding, and teaching. Given how fascinating and
      fruitful such inquiries can be, one wonders why they have had a mostly episodic
      place in teaching. I submit that at least some limitations resulted from an
      emphasis on what I would loosely call "content" and, related to it, on
      comprehensive "formulations" of a single literary character. This paper argues
      instead for a shift in focus onto "process" and situations created by particular
      interactions between the characters. Rather than pursue "the psychology of the
      individual characters; what they are like, what makes them what they are, what
      intentions, often apparently not conscious, seem to motivate their actions and
      attitudes" (Silberger 1973), I would look instead at what characters do (what
      they say, what they appear to emote and think) in response to each others' speech
      and imputed feelings and designs. The give-and-take entailed in the collision of
      their wishes, needs, and pasts at specific points in the evolution of the plot,
      and their reciprocal (mis)perceptions and (mis)interpretations, is especially
      relevant to understanding and teaching what is often thought to be the most
      complex aspect of being/becoming a psychiatrist, namely, comprehending and
      managing the emotional valences of the therapist-patient relationship. While such
      interactions are often explicit in, or can be adduced from, novels, short
      stories, or poems, the one form to which they are intrinsic is drama.

PMID- 14587358
TI  - Unconscious communication and literature.

PMID- 14587359
TI  - Minor physical anomalies in schizophrenic patients and normal controls.
AB  - The aim of the study is to investigate the rate and topographical pattern of
      minor physical anomalies in schizophrenic patients and normal subjects and
      determine their value in predicting the patient-control status. Seventy-six
      schizophrenic inpatients (43 men, 33 women) and 82 normal control subjects (42
      men, 40 women) were examined for minor physical anomalies on the Waldrop scale.
      Schizophrenics showed a higher rate for almost all examined anomalies, the
      differences reaching statistical significance for six of them: fine electric
      hair, epicanthus, high/steepled palate, tongue with smooth/rough spots, third toe
      the second, and big gap between I and II toes. They have significantly higher
      values for 5 out of 6 body regions and for the total anomalies score. Anomalies
      in schizophrenics show higher prevalence in the craniofacial complex than the
      periphery, but the periphery is also considerably stigmatized. Seven anomalies
      distinguish patients from controls, classifying correctly 81.6% of the patients
      and 82.9% of the controls. Some anomalies show an almost equal rate in the
      schizophrenics and the controls, while the rate of others is more than 10 times
      greater in the patients (odds ratios range: 1.0 to 10.9). Viewed within the
      multifactorial-polygenic threshold model of liability to a disease, minor
      physical anomalies might reflect a type of neurodevelopmental risk factor, which
      by interaction with other genetic or environmental factors could result in
      passing a threshold and producing symptoms of the disorder, at least in one
      subpopulation of schizophrenics.

PMID- 14587360
TI  - Music effects on EEG in intrusive and withdrawn mothers with depressive symptoms.
AB  - The EEG patterns of 48 intrusive and withdrawn mothers with depressive symptoms
      were assessed following a 20-minute music session to determine if the music had
      mood-altering effects. Half the mothers listened to classical music while half
      listened to rock music. Intrusive mothers were expected to have more positive
      responses and more symmetrical EEG following the calming classical music, while
      withdrawn mothers were expected to have a more positive response and symmetrical
      EEG following the energizing rock music. Although more positive EEGs were noted
      for rock music in both groups, only the withdrawn mothers showed a significant
      change in EEG toward symmetry following rock music, and only the intrusive
      mothers showed a decrease in cortisol levels following the rock music. Their
      State Anxiety Inventory (STAI) anxiety levels also decreased, while the Profile
      of Mood States (POMS) depressed mood levels decreased significantly for all four
      groups following music.

PMID- 14587361
TI  - Parent-daughter discrepancies in perception of family function in bulimia
      nervosa.
AB  - Eating disorders have traditionally been associated with disturbed family
      function. Most empirical data regarding this issue, however, were gathered from
      eating disorders patients. Attitudes, function, and inter-personal relationships
      were examined within 16 families with a member suffering from bulimia nervosa
      (BN) and compared to 16 matched healthy families. Perception of family function
      was significantly more derogatory in bulimic subjects than in their parents,
      while in control subjects and parents, perception was largely congruent. Subjects
      suffering from BN perceived their families as less cohesive, adaptable, and
      supportive than did healthy subjects. No such difference in perception of family
      function was observed between parents of respective groups. This preliminary
      study shows that parent-daughter discrepancy in perception of family function may
      prove more characteristic of eating disorder families than any particular
      deficit. Future research should aim to replicate these findings, incorporate them
      into treatment paradigms, and employ them to monitor treatment outcome.

PMID- 14587362
TI  - Coping with voices: selective attention training for persistent auditory
      hallucinations in treatment refractory schizophrenia.
AB  - Attentional difficulties in people with schizophrenia are common and can be
      disabling. A number of cognitive rehabilitation interventions aim to improve
      attention span by having patients practice paying attention to various types of
      stimuli for increasing lengths of time. However, such interventions typically
      assume that the attention deficit is a form of negative symptom, reflecting a
      reduced ability to maintain an attentional focus. In the following case study, we
      describe a cognitive intervention for a patient whose inability to pay attention
      was the result of persistent, distracting, and disabling auditory hallucinations.
      The dichotic listening paradigm was modified to enable the patient to repeatedly
      practice attending to a source of relevant information, while ignoring irrelevant
      information that was gradually introduced to one, two, and then three spatial
      locations. A graded technique was used wherein difficulty level (i.e., number of
      stimulus sources and stimulus intensity) was increased only after near perfect
      performance was achieved on prior trials. Embedding this intervention within the
      context of a therapeutic relationship led to clear improvement in task
      performance over time, with concomitant better attentiveness on the inpatient
      unit, and an improved ability to engage in interviews at residential settings,
      leading to subsequent hospital discharge.

PMID- 14587363
TI  - The effect of paroxetine on Taijinkyofusho: a report of three cases.
AB  - Taijinkyofusho is a culture-related syndrome conceptualized in Japan. While
      previous studies suggest its psychopathological similarities to social phobia and
      obsessive-compulsive disorder, introspection regarding shame and low self-esteem
      is particularly linked to Japanese culture. We present three cases of
      Taijinkyofusho: Cases 1 and 2 show neurotic features while Case 3 shows
      delusional thoughts. Paroxetine was used for treatment but was productive in only
      the first two cases. Phobic and obsessive thought patterns were altered in Cases
      1 and 2, suggesting that the significant core symptoms were responding to the
      treatment. In the future, large-scale pharmacological studies will be necessary
      to investigate treatment outcomes Taijinkyofusho. Such studies would contribute
      to providing information for effective treatment as well as for examining
      relationships between Taijinkyofusho and related disorders.

PMID- 14587364
TI  - [Education in internal medicine: usefulness of "case reports"].

PMID- 14587365
TI  - [Periarteritis nodosa and hepatitis C: a fortuitous association?].
AB  - Polyarteritis nodosa is a vasculitis of unknown origin which can be rarely
      associated with hepatitis B. A exceptional clinical situation of a polyarteritis
      nodosa associated with hepatitis C is described. This case is also the occasion
      to review the clinical manifestations, the diagnostic strategy und the
      therapeutic options of this rare vasculitis.

PMID- 14587366
TI  - [Hyponatremia: an unusual case report].
AB  - Hyponatremia is a frequent finding and asks for a rapid diagnostic evaluation. We
      report a case of recurrent hyponatremia secondary to an adrenal insufficiency of
      medicamentous and tuberculous origin. This case illustrates the importance of a
      rapid etiologic diagnosis of hyponatremia and allows us to review adrenal
      insufficiency of tuberculous origin. It also stresses the danger of potential
      drug interactions in case of corticosteroid substitution.

PMID- 14587367
TI  - [Can we predict the risk of malignancy associated with dermatomyositis?].
AB  - Dermatomyositis (DM) and polymyositis (PM) are idiopathic inflammatory muscle
      diseases which remain a therapeutic challenge. The association between DM and
      malignancy is relatively well established while this relationship is weaker with
      PM. The clinical management and research for an occult malignancy as well as the
      follow-up of patients with DM or PM is a matter of debate. Herein we report a
      case of DM who, despite an extensive clinical, radiological and biological work
      up developed an occult ovarian cancer 12 months after the initial diagnosis. This
      case report was used as support to review the actual expert recommendations for
      the search of an occult malignancy in presence of DM or PM.

PMID- 14587368
TI  - [Liver abscess: a practical approach].
AB  - The management of a liver abscess suspected on the basis of clinical and
      radiological findings is radically different depending on its amoebic or pyogenic
      etiology. Medical management is usually enough to treat amoebic abscess, the
      prognosis of which is excellent while percutaneous aspiration puncture, drainage
      and antibiotics is the rule in pyogenic abscess, the prognosis of which depends
      on the quickness of diagnosis and risk factors associated. This article first
      relates a case of liver abscess we had in our service and then propose, on the
      basis of a literature review, a synthesis of the different characteristics,
      diagnostic and therapeutic approaches and follow-up of amoebic and pyogenic liver
      abscesses.

PMID- 14587369
TI  - [Hypophosphatemia and refeeding syndrome: a severe and underdiagnosed adverse
      effect].
AB  - A 68-year-old woman was hospitalised because of generalised weakness and
      development of confusional state, related to severe hyponatremia, probably due to
      an eating disorder with malnutrition. During the first days of hospitalisation
      the patient eats surprising large amounts of food. The worsening of the
      confusional state in spite of normalisation of natremia, and the progressive
      development of anemia and thrombocytopenia, leads to the discovery of a new onset
      severe hypophosphatemia. The rapid fall in plasma levels of phosphorus, magnesium
      and potassium are the main futures of the refeeding syndrome. Its clinical
      manifestations are neurological, muscular, haematological and renal. The
      development of this syndrome is associated with a high mortality. The refeeding
      syndrome is seen when carbohydrates are introduced after a period of
      malnutrition. Identification of patients at risk for the refeeding syndrome
      (anorexia nervosa, chronic alcoholism, chronic malnutrition, elderly patients,
      oncology patients), the introduction of cautious progressive nutrition and the
      careful monitoring of vital signs, electrolytes levels and fluid balance, allows
      to prevent morbidity and mortality of this syndrome.

PMID- 14587370
TI  - [Torsade de pointes: a severe and unknown adverse effect in a patient taking
      methadone].
AB  - We present here the case of a young drug-addicted patient, who showed a cardio
      respiratory arrest attributed to a torsade de pointe-type ventricular arrhythmia.
      After excluding the usual causes of such arrhythmia, we concluded that it was
      consecutive to high-dose methadone intake. Methadone can induce torsade de pointe
      through two mechanisms: a QT interval prolongation secondary to a bradycardia or
      a prolongation of the myocardial action potential. When prescribing methadone,
      one should avoid association with other CYP3A4 inhibiting drugs and, if higher
      doses are necessary, perform regular EKG screening.

PMID- 14587371
TI  - [Biotyping and molecular phenotypic characterization of Bordetella
      bronchiseptica].
AB  - In the present study biochemical tests and outer membrane protein profile (OMP)
      capacity for typing Bordetella bronchiseptica field isolates were evaluated. The
      biochemical tests were performed by API 20NE system. OMP enriched fractions were
      obtained from cultures under virulent and modulated conditions and were analyzed
      by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). We have
      identified five patterns by differences in the bands in the 85-95 kDa region
      (alpha, beta, gamma, delta and epsilon) from virulent cultures; and three
      different patterns by the flagellin expressed isotype from modulated cultures (A:
      40 kDa, B: 45 kDa, and C: 40 and 45 kD simultaneously). Isotypes alpha, beta and
      gamma were linked to isotpye A, isotype delta to B and C, and isotypes epsilon to
      B. There is no evident correlation between characterized isotypes and the origin
      of the isolate. Nitrate reduction was the unique variable biochemical
      characteristic, only observed in rabbit isolates. It was possible to
      differentiate seven groups with the traits included in the study. The capacity of
      discrimination of the traits analyzed using the Hunter and Gaston index was
      0.829.

PMID- 14587372
TI  - [Evaluation of 2 hemoculture media for the isolation of Brucella spp.]].
AB  - The diagnostic efficiency of two hemoculture media for the detection of different
      species of Brucella strains was evaluated. Strains of Brucella melitensis,
      Brucella suis, Brucella abortus, Brucella ovis, and Brucella abortus S19 were
      used. Each strain was diluted in phosphate buffer saline (PBS) to obtain a
      concentration of 10(5) colony forming units/ml (CFU/ml). Blood from goats, pigs,
      cattle, and sheep was mixed with the bacterial suspension to obtain a final
      concentration minor or equal to 10(3) CFU/ml. These blood samples were inoculated
      into the following media: (i) Hemobrucella (HB), (ii) Tryptose citrated broth 2%
      (CTB), and (iii) Controls without blood for B. melitensis and B.suis. Subculture
      in dishes and CFU/ml counts were made at the 1st, 3rd, 8th, 10th, 20th, and 30th
      post-inoculation (PI) day. Best results were obtained in the HB medium for all
      strains, except for B. suis, which due to the presence of a contaminant did not
      reach its maximum development in this medium. All strains were recovered from
      both media at 24 h PI, except B. ovis that was isolated from HB at 72 h PI and
      was not recovered from CTB. All strains remained viable for a shorter period in
      CTB. Under the proposed experimental conditions the HB medium was more sensitive
      than CTB. Future experiments should evaluate the utility of this commercial
      medium in clinical cases of animal brucellosis.

PMID- 14587373
TI  - [Rennet production by Rhizomucor miehei NRRL 3169].
AB  - The production of rennet was studied, using different strains of the fungus
      Rhizomucor miehei. The selection and preservation of strains, type of growth,
      media design and operation conditions were evaluated. The experiments were
      carried out in Erlenmeyer flasks in rotary shaker at 250 rpm and 2.5
      eccentricity, and in mechanically stirred fermentors of the New Brunswick type,
      at 30 degrees C. In the studies concerning strain selection, the best strain was
      Rhizomucor miehei NRRL 3169. The major titles of enzyme were obtained in batch
      process at 168 h, with 884 SU/ml, whereas in mechanically stirred fermentors the
      best value was 1160 SU/ml. These values were far more superior to former ones
      published by various experts.

PMID- 14587374
TI  - [Evaluation of API 20 NE (version 6.0) in rare Gram-negative non-glucose
      fermenting bacilli].
AB  - The ability of the API 20 NE method (6.0 version, bio-Merieux, Marcy L'Etoile,
      France) to identify 188 strains of gram negative nonfermentative bacilli (NFB)
      was evaluated (Fenazinic pigment producing Pseudomonas aeruginosa and
      Acinetobacter spp. were excluded). These were isolated from patients treated at
      the Hospital de Clinicas Jose de San Martin of the University of Buenos Aires
      during the period 1996-2001. Strains were identified according to the
      Schreckenberger P testing method. Out of 188 NFB strains, 175 (93.09%) were
      correctly identified by the API 20 NE method at the genus and species level (IC95
      = 88.47-96.27) while 61 (32.45%) required additional testing for correct
      identification. Thirteen strains (6.91%; IC95 3.73-11.53) could not be correctly
      identified and none of them were classified as "non identified". The API 20 NE
      method is a practical, easy to handle, fast and useful system for the
      identification of NFB since conventional manual methods take longer and require
      many biochemical, enzymatic and physiological tests which are sometimes not
      available depending on the size and capability of the laboratory. Although it is
      easy to handle, the API 20 NE identification system must be interpreted by an
      expert microbiologist who must compare the results obtained by this system with
      the information provided by the distinctive cultures and mobility patterns of
      these organisms.

PMID- 14587375
TI  - [Development of a multiple PCR method for the identification of Ureaplasma parvum
      and Ureaplasma urealyticum].
AB  - Ureaplasma parvum and Ureaplasma urealyticum, also known as biovar parvum and
      biovar T960, respectively, could be associated with several disorders in men,
      women, and mainly, in newborn children with under weight. Several methods have
      been developed in order to identify the species or biovars of ureaplasmas. We
      developed a Multiplex-PCR method using the UPS-UPSA and UUS2-UUA2 primers,
      specific for U. parvum and U. urealyticum, respectively. This Multiplex-PCR
      method was used to identify cultures of clinical positive samples to Ureaplasma
      spp. by the "MYCOFAST Evolution-2" Kit. Of 56 positive cultures to Ureaplasma
      spp. from newborn children, 70% were U. parvum and 30% U. urealyticum; in 76
      positive samples in women, 83% corresponded to U. parvum and 17% to U.
      urealyticum, while in 63 positive samples of men, 76% identified U. parvum and
      24% U. urealyticum. The PCR-multiplex method showed specificity for the
      identification of the biovars or species of ureaplasmas of clinical interest.

PMID- 14587376
TI  - Humoral immune response to infectious agents in aborted bovine fetuses in
      Argentina.
AB  - The purpose of this study was to characterize the exposure of bovine aborted
      fetuses from beef and dairy herds of the humid pampas of Argentina to different
      infectious agents by the evaluation of fetal fluid antibodies. Presence of fetal
      antibodies to bovine viral diarrhea virus genotype 1 (BVDV-1), bovine herpes
      virus type 1 (BHV-1), Leptospira interrogans, Brucella abortus, and Neospora
      caninum was determined. Of the 95 fetuses processed, 66 came from 49 beef herds
      and 29 from 12 dairy herds. The average gestational age of the aborted fetuses
      was 7.1 months. Antibodies to the mentioned agents were detected in 65 of the 95
      fetal fluids (68.4%). In addition, antibodies to more than one infectious agent
      were detected in 32 fetuses (33.7%), suggesting fetal exposure to multiple
      antigens during gestation. There were antibodies to BVDV-1, BHV-1, N. caninum and
      Leptospira interrogans in 43 (45.2%), 29 (30.5%), 26 (27.4%) and 5 (5.2%)
      specimens, respectively. Antibodies to B. abortus were not detected in any of the
      fetal fluids. The results of this study provide information on the determination
      of antibodies in fluids from bovine aborted fetuses exposed to different
      infectious agents in the region.

PMID- 14587377
TI  - [Evaluation of synthetic peptides for the detection of antibodies against human
      immunodeficiency virus].
AB  - The serologic diagnosis of human immunodeficiency virus (HIV) infection is
      currently done by detecting the presence of antibodies against the different
      antigenic viral proteins through immunoassays and later confirmation by Western
      blot. Several types of antigens can be used in immunoassays, but recombinant
      proteins and synthetic peptides are the most frequently used. In this paper,
      peptides mimicking antigenic regions from p24 (region 196-224), gp41 (region 600
      614) and gp120 (region 303-338, Loop V3) proteins of HIV-1 have been used as
      antigens in an enzyme-linked immunosorbent assay and their reactivity was
      screened against a panel of positive and negative sera. Six antigenic mixtures
      containing different amounts of each peptide were prepared, and the one
      consisting of 1 microgram of gp41-15, 0.5 microgram of p24-1 and 0.5 microgram of
      gp120-1 per well has shown the best performance to differentiate positive and
      negative serum samples, with sensitivity and specificity values of 99.18% and
      100%, respectively. Considering the potential utilization of this system for
      screening of HIV infection, it would be relevant to evaluate the additional
      incorporation of sequences derived from Argentine local circulating viral
      variants to improve the diagnostic sensitivity of the assay, allowing the
      development of an ELISA based on specific viral sequences.

PMID- 14587378
TI  - [Malassezia species isolated from skin diseases in a care center in the city of
      Buenos Aires, Argentina].
AB  - The epidemiology of Malassezia genus is poorly understood; geographical and
      population factors might have influence on the species distribution. The aim of
      this work was to determine the frequency of Malassezia species involved in skin
      diseases in a diagnostic center at Buenos Aires City. From 02/01/1999 to
      10/31/2001, 456 skin specimens from 447 patients diagnosed as pityriasis
      versicolor, seborrheic dermatitis, foliculitis and atopic dermatitis, were
      analyzed by microscopic examination and culture. Malassezia spp was evidenced in
      255 skin samples (55.9%) by microscopic analysis but it could be recovered from
      only 99 (38.8%) specimens. Malassezia species were isolated from 10 (3.9%)
      scarring lesions that were negative by microscopy. Among 109 isolates, M.
      sympodialis (58.7%) was the most frequent, followed by M. globosa and M. furfur
      (18.3% and 9.2%). Unique isolates (0.9%) of M. obtusa, M. slooffiae and M.
      restricta were recovered. Eleven isolates (10.1%) could not be identified because
      they had lost viability in the culture. This is the first study on Malassezia
      species associated to skin diseases in Argentina; further screening including
      other geographic regions of the country is necessary in order to confirm these
      results.

PMID- 14587379
TI  - [Identification of Malassezia species by PCR-REA].
AB  - The genus Malassezia has acquired relevance in the last years for its
      pathological associations. Since 1996, the genus comprises M. pachydermatis, M.
      furfur, M. sympodialis, M. slooffiae, M. obtusa, M. globosa and M. restricta. The
      identification scheme based on morphological, physiological and biochemical
      characteristics does not resolve ambiguity between some species. The aim of this
      study was to find out a fast, specific and efficient methodology to distinguish
      between Malassezia species. Based on a previous technique for polymerase chain
      reaction-restriction enzyme analysis (PCR-REA), modifications were applied on DNA
      extraction and purification and the electrophoresis. These changes produced a
      cheaper, reliable and rapid method as identification procedure with easily
      defined results. The proposed modifications would allow a better knowledge on
      ecological and pathogenic roles of Malassezia, studies that have not yet been
      established.

PMID- 14587380
TI  - [Bacteremia in 2 hospitals in Rosario, Argentina].
AB  - Bacteremia is associated with high morbidity and mortality. Nosocomial bacteremia
      is associated with an attributable mortality of 35%. In order to characterize the
      etiological agent of bacteremia cases during two time periods, 6605 patients were
      studied as follows: 1) from 1980 to 1982 (n = 2401) and 2) from 1988 to 2000 (n =
      4204). A total of 596 cases of bacteremia were detected. The most frequent agents
      were Staphylococcus aureus, negative coagulase (CNS) Staphylococcus, Klebsiella
      pneumoniae and Escherichia coli. In the second period, an increase in the
      frequency of bacteremia caused by gram positive bacteria, particularly gram
      positive cocci, was noted. Conversely, gram negative bacteria diminished
      significantly in the second period, specially enterobacterial species.
      Methicillin-resistant S. aureus and CNS were significantly more frequently
      isolated in the second period. Infrequent agents of endocarditis, such as
      Actinobacillus actinomycetemcomitans, Haemophilus aphrophilus, and
      Corynebacterium urealyticum, were isolated.

PMID- 14587382
TI  - [Beethoven's deafness: the basis of hearing].

PMID- 14587381
TI  - [Exanthematous outbreak caused by human parvovirus B19 in a school in Banderalo,
      Argentina].
AB  - We report an exanthematic outbreak in a school of Banderalo town, located in the
      district of General Villegas, Buenos Aires province, Argentina. This outbreak
      affected 21 individuals, with a wide range of age (out of a total population of
      1400). The observed clinical manifestations were exanthema and in some cases
      fever, asthenia, arthropathies and myalgia. The presence of specific IgM
      antibodies against measles, rubella and human parvovirus B19 were investigated.
      Analysis of IgM antibodies to parvovirus B19 by ELISA was positive in 90.8% of
      the cases and viremia was detected in 66.7% of the patients by nested PCR. These
      results indicate that human parvovirus B19 was the etiologic agent of the
      outbreak and they confirm its circulation in Argentina. Moreover, this study
      demonstrates that PCR may be useful for the study of transmission foci and of
      individuals with prolongued clinical manifestations. We consider that it is
      necessary to include the differential diagnosis of human parvovirus B19 in the
      surveillance of exanthematic virosis.

PMID- 14587383
TI  - [Time factors in postoperative radiotherapy in the years 1986-19990 and 2000
      2002].
AB  - Postoperative radiotherapy plays an important role in management of advanced
      laryngeal cancer. Numerous retrospective data has given strong evidence that
      prolongation of treatment time of radiotherapy has negative influence on
      treatment results. Generally, it might be concluded that each additional day of
      irradiation is connected with drop of locoregional control in range from 1% to
      2%. In this paper, the duration time and frequency of gap which occurred during
      postoperative radiotherapy of the laryngeal cancer in the following two time
      periods were compared: 1986-1990 (group I) and 2000-2002 (group II). An analysis
      indicated that in the I group of patients gaps during the course of postoperative
      radiotherapy were noted in 52% (160/311 patients) and in the group II in 26%
      (71/270 patients). The median time of the gap dropped from 8.3 days to 4.2 days.
      In the same time the percentage of gaps due to acute side effects was reduced
      from 30% (94/311) to 9% (24/270) and in addition the reduction of the time of
      gaps by 4.1 days was observed. The significant reduction of the time of gaps due
      to breakdown of therapeutic machine was observed, but the number of gaps with
      this reason was generally low. In the II group of patients treated in years 2000
      2002 the percentage of gaps caused by holidays increased from 10% (33/3110) to
      14% (39/270). The median time of gap in the same time was lowered by 1 day. In
      conclusion, during the last decade, the length of the postoperative radiotherapy
      for patients after total laryngectomy due to advanced laryngeal cancer was
      reduced. Still is a place for additional time reduction of gap by intensification
      of patient's medical care during irradiation and logistic improvement in
      patient's care.

PMID- 14587384
TI  - [Treatment of tracheal stenosis or obliteration].
AB  - The authors present the material of 55 patients, who were treated in ENT
      Department of Medical University of Bydgoszcz between 1992 and 2002. The authors
      distinguish four groups of patients: 1) with the tracheal stenosis or
      obliteration, who had to be treated by excision of the stenosed part of the
      trachea, 2) with the tracheal stenosis treated with laser CO2 beam, 3) with the
      tracheal stenosis treated by laryngectomy before, 4) not treated surgically
      because of different reasons. The authors present diagnostic and therapeutical
      problems in each group on the basis of the observed material. They also discuss
      application of laryngeal neurostimulator during the operation of cutting out the
      stenotic or obliterated part of trachea. On the basis of the analysis of
      presented material they express opinion that the term "tracheal stenosis"
      includes a number of different pathological cases requiring different diagnostic
      and treatment procedures. They also think that pathological changes called
      "tracheal stenosis" should be treated in clinical centers with long experience
      and proper equipment.

PMID- 14587385
TI  - [Enlarged vestibular aqueduct syndrome in patients with hypoacusis and deafness].
AB  - In 1978 Valvassori and Clemis have reported that enlarged vestibular aqueduct can
      cause progressive perceptive hearing loss and finally deafness. AIM: Analysis of
      CT scans of patients with cochlear implants. Analysis of radiological data of 120
      implanted patients was performed. CT examinations were performed during
      qualification to cochlear implantation. Most of the CT scans were performed using
      high resolution computed tomography (HRCT). A special attention was paid to
      patients with progressive perceptive hearing loss and CT of two patients with
      "gusher" during CI surgery. In one case (6-years old girl with bilateral profound
      perceptive hearing loss diagnosed in 2nd year of age) an enlarged vestibular
      aqueduct was found radiologically. In the second case (16 years old girl with
      progressive perceptive hearing loss since 1st year of age) no enlarged vestibular
      aqueduct was detected. Diagnostics and treatment of enlarged vestibular aqueduct
      syndrome are presented.

PMID- 14587386
TI  - [Clinical response to photodynamic therapy in premalignant lesions and advanced
      head and neck carcinomas].
AB  - The main advantage of PDT in laryngology seems to be its non-invasiveness and the
      possibility of using it despite of previous application of conventional methods.
      In the study application of PDT in two separated groups of patients, i.e. 8
      patients previously treated by surgery and radiotherapy with local recurrence
      (SCC) or with advanced primary lesion and 12 patients with oral leucoplakia. In
      the first group delta-aminolevulenic acid (ALA) was administered orally, while in
      second one an ointment containing 10% ALA was applied locally. In the both groups
      prior to irradiation the tissue level of protoporphyrin IX was verified by
      adapted Xillix LIFE machine. All treated lesions were irradiated with argon
      pumped dye laser. In leucoplakia group complete response was achieved in 10 out
      of 12 treated patients. In group of advanced cancers the only partial response
      was obtained--the diminution of cancer ulceration was observed. On the basis of
      our preliminary results the usefulness of PDT may be suggested in eradication of
      premalignant lesions of oral cavity and palliation of advanced cancers within
      pharynx and larynx.

PMID- 14587388
TI  - [Trans-facial and cranio-facial approach and resection of the skull base tumors].
AB  - The paranasal sinus cancers comprise about 10% of all head and neck neoplasms.
      There are 80% of SCC among them. Paranasal sinus cancer is difficult to treat
      with surgery due to the anatomic integration of sinuses into the cranial base.
      Suborbital approach allows to simultaneous resection of the tumor from sinuses
      and anterior cranial fossa. The excision of the nasofrontal bone lamella gives a
      chance to orbital decompression and optic nerve decompression as well and opening
      the anterior cranial fossa through posterior wall of the frontal sinus. The goal
      of the study was to present cases showing advantages and effectiveness of this
      kind of surgical procedure.

PMID- 14587387
TI  - [Markers of epidermal proliferation in middle ear cholesteatoma].
AB  - Middle ear cholesteatoma is characterized by the presence in the middle ear
      cavity of a stratified squamous epithelium with keratin deposits which by
      constant proliferation leads to extensive bone destruction. The goal of this
      study was to evaluate, by immunohistochemical study, the expression of epithelial
      markers of proliferation--Ki-67 and PCNA in the matrix of cholesteatoma. The
      materials used in this study were 16 acquired cholesteatoma tissues collected
      from patients in the age 6-17 years during surgery. The specimens from the skin
      of the external ear canal were employed as the control. In the
      immunohistochemical specimens staining intensity and distribution of Ki67 and
      PCNA positive cells in various layers of the epithelium were assessed in three
      stages scale. The results were compared to the clinical parameters such as--type
      of cholesteatoma (pars flaccida or tensa), presence of ear discharge, degree of
      ossicular destruction and involvement of attic and mastoid. In the cholesteatoma
      matrix Ki-67 and PCNA positive cells were present in basal and suprabasal cell
      layers and also more superior layers, unlike the control skin were only basal
      cells show positive staining. The number of positive cells and intensity of
      staining was also greater in the cholesteatoma matrix than in skin of external
      auditory meatus. No correlation was found between results of immunohistochemical
      examination and clinical parameters.

PMID- 14587389
TI  - [Inverted papilloma of the nose and paranasal sinuses: diagnosis and treatment].
AB  - The authors present a retrospective study of 6 patients with inverted papilloma,
      which appeared in the material of ENT Clinic in Wroclaw in years 1996-2001. In
      the group of treated patients, we can recognize 5 men and one woman at the age
      between 42 to 82. Average age amounted to 62 years. At all the patients the
      papilloma inversum was diagnosed completely accidentally, during
      histopathological examination, after having polypectomy or Calwell-Luca
      operation. Operating treatment was proceeded by performing the CT or NMR test. In
      four cases the Denker's operation was done, in one case More's and in another one
      we performed the endoscopy operation (limited changes to ethmoidal labyrinth).
      The patients stay under the observation for 8 months to even 5 years. In one case
      we observed a relapse, which occurred after 8 months (patient after the Moure's
      operation). In all the rest cases a relapse was not identify.

PMID- 14587390
TI  - [Image cytometry appliance in chronic tonsillitis].
AB  - Enlargement of palatinar tonsils in the course of chronic inflammatory process
      has been thought till now to reflect pronounced lymphocyte proliferation even if
      such mechanism fails to explain the persistent increase in size of the organ. The
      studies were performed on 92 tonsils obtained from 4 to 16 years old children in
      whom the tonsils were removed due to chronic inflammatory processes in upper
      respiratory tract or in ears. Cell proliferation and apoptosis were evaluated by
      flow cytometry and by image analysis. The data show that apoptosis in the tonsils
      is accompanying lymphocyte proliferation in the course of chronic inflammatory
      process. Evaluation of homeostasis in palatine tonsils could be helpful in
      referring children for tonsillectomy. Imagine analysis may objectivize and
      specify diagnosis of chronic tonsillitis.

PMID- 14587391
TI  - [Open and closed laryngeal injuries].
AB  - Treatment and results of 13 laryngeal and trachea traumas have been presented.
      All patients were operated in 24 hours after the injury. We had good results,
      only two patients had vocal chord paralysis. After phoniatric rehabilitation they
      regained good voice.

PMID- 14587392
TI  - [Preliminary results of objective audiological assessment of children with
      hearing impairment selected in neonatal hearing screening].
AB  - The aim of the paper was to present the results of the objective audiological
      assessment of 48 babies and infants at the age of 1-16 months, referred the
      Department of Phoniatrics and Audiology in Poznan (Poland) from January 2001 to
      July 2002. The children were selected in neonatal hearing screening, based on the
      OAE, questionnaire of hearing loss with high risk factors. We discuss high
      percentage of false positive results of OAE, late referrals for hearing
      screening, difficulties of follow-up.

PMID- 14587393
TI  - [The correlation between subjective and objective voice evaluation in organic and
      functional larynx disorders].
AB  - The aim of this research is to develop and introduce into phoniatric diagnostic
      procedures the complex methodology of vocal function assessment, on the basis of
      comparison of subjective and objective voice estimation. The set of complex voice
      evaluation ought to include perceptual examination of the voice quality with
      quantitative GRBAS scale as a subjective method, vocal folds vibrations in
      videostroboscopy as a quasi-objective method and acoustic voice estimation in
      Multi Dimensional Voice Program (MDVP) as an objective method. The basic
      assumption of this report is to prove correlation existence for vocal folds
      vibration quality in videostroboscopy, parameters describing acoustic wave
      generating by vibration system in larynx (MDVP) and perceptual subjective voice
      assessment (GRBAS scale) in organic and functional voice disorders. Research was
      conducted on 100 subjects (65 with organic and 35 with functional voice
      disorder), aged 7-74 years randomly chosen from population of patients treated at
      the Department of Phoniatrics and Audiology, Karol Marcinkowski University School
      of Medical Sciences in Poznan in 1996-2001 and 60 subjects as a control group
      without any voice disorders according to phoniatric examination. The research
      methodology include perceptual voice evaluation based on Japanese (Hirano) GRBAS
      scale adapted to Polish language, in scale 0 to 3 as well as the vibrations of
      vocal folds in videostroboscopy with attempt at quantification (scale 1 to 3) of
      selected measure and for acoustic analysis of Multi Dimensional Voice Program
      (MDVP) for 17 estimated parameters. Due to results and statistic analysis the
      own, new scale of dysphonia severity was introduced.

PMID- 14587394
TI  - [Transtympanic steroid application in sudden deafness].
AB  - The paper presents the results of transtympanic steroid therapy for sadden
      sensorineural hearing loss in 20 patients. All patients previously underwent a
      full conventional treatment, without the beneficial effect. Patients were
      classified into two groups: the first one consisted of 16 patients who received
      intratympanic Dexaven application just after termination of conventional
      treatment. The second group received intratympanic treatment 1 or more months
      after the conventional therapy had been finished. The pattern of intratympanic
      Dexaven application is presented. The results of treatment are promising (hearing
      improvement in 7 cases) and the method is both minimally invasive and
      inexpensive.

PMID- 14587395
TI  - [Plan of therapy and rehabilitation in stuttering patients].
AB  - The aim of the paper is to present the program of therapy and rehabilitation in
      stuttering patients based of the digital speech aid. The device has been applied
      to 130 patients aged 6-47 y.o. 85% of the patients had statistically significant
      instant improvement of speech fluency after application of digital speech aid.
      After completing diagnostic process, the patients were enrolled for the
      rehabilitation program which comprised of training with the use of speech aid,
      speech therapy, psychotherapy, audio-psycho-linguistic stimulation with the use
      of the Tomatis Method, physiotherapy, relaxation exercises, phoniatric
      rehabilitation and medical therapy. After 6 months of therapy and rehabilitation
      a statistically significant improvement of speech fluency was found in 124
      patients, i.e. in 96%. The therapeutic programme based on the use of digital
      speech aid proves effective for majority of stuttering patients.

PMID- 14587396
TI  - [Histomorphology of the pharyngoesophageal sphincter as prognostic factor of
      developing esophageal speech].
AB  - Histomorphologic evaluation of the pharyngoesophageal sphincter (pes) in the
      decreased persons aged 11-82 was done. These persons, in the lifetime, never
      suffered from: a) neurologic diseases (among others-myasthenia, progressive
      muscle atrophy), b) neoplasm of the esophagus, c) dysphagia. The aim of the
      report was the explanation whether the degenerative changes in pes, seen in the
      course of ageing, should be included into the risk factors of the high pressure
      occuring in its area after total laryngectomy. The analysis of the
      histopathological specimens revealed that after 40 years of age connective tissue
      in the pes is spreading and the number of muscular fibers is decreasing. Till 60
      years of age the degenerative process in pes is very differentiated. Some
      histopathological specimens, in persons of this age section, didn't differ much
      from those seen in young cases. In the following decades o life degenerative
      process intensifies successively. In the histopathological specimens intensive
      proliferation of the fibrotic and fat tissue was found and considerable decrease
      of muscular fiber number. The investigations on risk factors of high pressure in
      the area of pes (results made know in paper given for print) revealed that in
      elder patients after total laryngectomy, its values are higher than in young
      ones. In patients till 55 years of age, in 72.29% (n = 26/36) of examined cases,
      the pressure in the pes area didn't exceed 3.99 kPa (30 mmHg). In the age of 55
      years and above such a pressure was observed only 39.1% (n = 18/46) of examined.
      Degenerative changes in pes, depending on age, can be in part of patients
      (particularly in elder ones) one of the risk factors of the high pressure in the
      pes area, which should be taken in account in prognosis of esophageal speech
      mastering by the patient.

PMID- 14587397
TI  - [Schwannoma of the cervical plexus: a case report].
AB  - A case of 70 years old man with cervical plexus schwannoma is presented. The
      tumor was removed surgically using extracapsular technique. The differential
      diagnosis and surgical techniques are discussed. The pre-operative symptoms,
      impressions and post-operative neurological status were shown and discussed. The
      review of literature is presented.

PMID- 14587398
TI  - [Malignant schwannoma of infraorbital nerve].
AB  - Schwannoma of the head and neck may develop from many nerves, i.e. cranial or
      spinal. The authors described malignant schwannoma of infraorbital nerve. Patient
      was treated by combined method: in first step chemotherapy, in second surgical
      excision with 2 year disease-free survival.

PMID- 14587399
TI  - [Intracranially extended nasopharyngeal angiofibroma treated surgically and by
      radiotherapy].
AB  - A case of nasopharyngeal angiofibroma with intracranial extension is presented.
      The parasellar extension was demonstrated on CT and MRI scans after four
      operations performed in two centres. The boy was radiated (42 Gy/t). Two and a
      half years follow up using MRI showed gradual regression of the tumour down to
      minimal enhancement in the parasellar region.

PMID- 14587401
TI  - [19th century achievements of physicians in the diagnosis and treatment of ear
      polyps].
AB  - The treatment of nasal polyps in the past is described. The role of such
      physicians as Aetius of Amida, Paul of Aegina, Guy de Chauliac, Gabrele Fallopio,
      Fabricius Hildanus are depicted, the significance of such XIX century physicians
      as Joseph Toynbee, Anton von Troeltsch, Joseph Gruber, Adam Politzer, Friedrich
      Voltolini and Bronislaw Taczanowski, Teodor Heiman at Polish territories are
      presented with full particulars. The problems of pathological anatomy,
      symptomatology and especially the treatment of aural polyps is strongly pointed
      out. The significance Bonnafont's instrument, Blake's and Wilde's nooses,
      galvanocaustic operations are described in more detail. The danger of those
      operations is pointed out.

PMID- 14587400
TI  - [Bezold's abscess: a rare complication of otitis media].
AB  - The authors present the case of a 21-year-old female in who, during the course of
      cholesteatoma, extracranial complications occurred twice in the form of Bezold's
      abscess. This type of the complication of otitis media occurs extremely rare.
      Medical literature has recorded about 20 cases of such complications. Due to
      commonly applied antibiotic therapies, extracranial and intracranial
      complications are rarely recorded in the course of otitis media, their mortality
      rate, however, amounts to a dozen or so per cent. The paper presents the way in
      witch the infection of otitis media spreads towards the neck. The authors stress
      the significance of computer tomography in diagnostic. Radical mastoidectomy and
      exploration of the neck were performed on the patient. Antibiotic regimens were
      based on antimicrobial sensitivity patterns. Presently, the patients is under
      constant laryngologist observation.

PMID- 14587402
TI  - [Otolaryngological assessment and treatment of health status of the district
      military personnel and the suitability for military service according to
      recruitment commission in Lodz].

PMID- 14587403
TI  - [Late assessment results of surgical treatment of hypertrophic laryngitis in
      otorhinolaryngology].

PMID- 14587404
TI  - [Professor Andrzej Lepkowski's anniversary].

PMID- 14587405
TI  - [Abdominal applications of multislice CT].
AB  - Multislice helical CT has made it possible to obtain thinner images with wider
      coverage at a higher speed in comparison with single-slice helical CT and has
      improved temporal and spatial resolution. The higher speed available with
      multislice CT has enabled double arterial phase imaging of the liver and both
      arterial and pancreatic phase imaging of the pancreas in a single breath-hold.
      Just as multislice CT has improved the diagnoses of hepatic tumors and pancreatic
      tumors, it has also improved the quality of three-dimensional imaging, such as
      multiplanar reformation and CT angiography, by its thinner images. CT angiography
      is replacing conventional angiography for presurgical evaluation.

PMID- 14587406
TI  - [Cardiac imaging including nuclear medicine, MRI, and MDCT].
AB  - Nuclear cardiology has played a significant role in the diagnosis and risk
      stratification of patients with coronary artery disease. MRI and multidector-row
      CT (MDCT) has recently been introduced in the field of clinical cardiology. For
      the management of patients with suspected coronary artery disease, it is
      important to understand the advantages and disadvantages of various imaging
      modalities. This review discusses the current roles and problems of these imaging
      modalities.

PMID- 14587407
TI  - [Spinal epidural hematoma: relationship between imaging findings and neurological
      outcomes].
AB  - PURPOSE: The purpose of this study was to evaluate the usefulness of CT or MR
      imaging findings in patients with spinal epidural hematoma (SEH) for predicting
      neurological outcome. MATERIALS AND METHODS: MR images of our six patients with
      SEH were evaluated retrospectively: complete recovery was achieved in two
      patients; paresis remained in two patients; and paraplegia remained in two
      patients. The ratio of the maximum anteroposterior diameter of the SEH to that of
      the spinal canal was calculated in each patient on midline on axial images in our
      six patients and 23 previously reported patients. RESULTS: Among our six
      patients, the ratio was less than 60% in two patients with total recovery,
      whereas all four patients with remaining motor impairment had ratios of 60% or
      more. Of 29 cases, 18 of 22 patients without residual motor impairment had ratios
      of less than 60%, but five of seven patients with residual motor deficits had
      ratios of 60% or more (p = 0.023). CONCLUSION: The degree of spinal cord
      compression by hematoma may be a prognostic factor in SEH.

PMID- 14587408
TI  - [Whether and under what conditions FDG-PET might be cost-effective in evaluating
      solitary pulmonary nodules depicted on lung cancer screening in Japan].
AB  - PURPOSE: To determine whether and under what conditions fluorine-18
      fluorodeoxyglucose positron emission tomography (FDG-PET) may be cost-effective
      in evaluating solitary pulmonary nodules depicted on lung cancer screening in
      Japan. MATERIALS AND METHODS: Three decision models for differentiating lung
      cancer from benign nodules were compared: CT alone, PET alone, and CT plus PET.
      The various paths of each strategy were dependent on variables determined from a
      review of the medical literature. Costs were based on Japanese health insurance.
      RESULTS: The prevalence of lung cancer among solitary pulmonary nodules detected
      on lung cancer screening was less than 10%. For this prevalence, the CT-plus-PET
      model was the cost-effective alternative to the CT-alone model (cost savings were
      yen 64,000 per patient) and provided greater accuracy (0.90 vs. 0.84). Both of
      these effects were the result of reducing the number of candidates who undergo
      unnecessary CT-guided or bronchofiberscopic biopsies or thoracotomy for a benign
      pulmonary nodule. CONCLUSION: The CT-plus-PET strategy is accurate and cost
      effective for the characterization of solitary pulmonary nodules detected on lung
      cancer screening in Japan.

PMID- 14587409
TI  - [New three-dimensional compensating filter for TBI using compu-former associated
      with RT LAN].
AB  - To shorten the TBI process, we developed a new device for making the three
      dimensional (3D) compensating filter that improves dose distribution. The dose
      distributions in the phantom and manufacturing time were compared between the new
      device and the previous one. Clinical evaluations included dose distribution in
      patients and the clinical rate of interstitial pneumonitis (IP). Our 3D
      compensating filter is made of polystyrene resin and gypsum. The filter was made
      after performing two procedures as follows. Patient data were measured by CT, and
      the 3D dose-distribution data and 3D compensating-filter data were obtained from
      the CT data by the 3D radiation planning system. We were able to produce the new
      3D compensating filter within about 4 hours, including all procedures. The
      average dose distribution to each site when the 3D compensating filter was used
      was 92.7% to the head, 102.1% to the thorax, 106.4% to the pelvis, 90.2% to the
      knee, and 93.8% to the ankle joint, when the scheduled dose was taken as 100%.
      Dose distribution was improved. IP occurred in 6 of 32 patients (18.8%). There
      was no significant difference between the TBI and non-TBI groups in the frequency
      of IP (p = 0.27).

PMID- 14587410
TI  - [The biological effect of the phosphatidylinositol 3-kinase wortmannin following
      thermal neutron irradiation].
AB  - PURPOSE: Wortmannin, a phosphatidylinositol 3-kinase inhibitor, has been found to
      inhibit DNA-dependent protein kinase (DNA-PKcs) and to be an efficient
      radiosensitizer. We investigated the radiosensitizing effect of wortmannin on
      cell killing by thermal neutrons and the occurrence of mutations at the HPRT
      locus of CHO cells. MATERIALS AND METHODS: Wortmannin was added to cells at a
      final concentration of 20 microM two hours before irradiation. Cells were
      irradiated with thermal neutrons. The biological end point of cell survival was
      measured by colony formation assay. Mutagenicity was calculated from the mutation
      frequency at the HPRT locus. RESULTS: Wortmannin promoted cell death following
      thermal neutron irradiation especially in the absence of boron. However,
      mutagenicity was decreased by the wortmannin treatment. CONCLUSION: Our results
      suggest that the inhibition of DNA-PKcs by wortmannin would be an effective
      radiosensitizer for BNCT and might bring about a reduction in the frequency of
      mutation by blocking the mis-joining of DNA damage during the repair process.

PMID- 14587411
TI  - [Effect of contrast material pushed with saline solution using dual injection on
      enhancement of aorta, portal vein, and liver parenchyma in multislice CT of the
      liver].
AB  - We evaluated the effect of the enhancement value of the abdominal aorta, portal
      vein, and liver parenchyma by the saline flush technique. One hundred eight
      patients who underwent multislice CT of the liver were randomly divided into four
      groups: 100 ml of contrast material (Iomeprol 300 mgI/ml or 350 mgI/ml) only and
      100 ml of contrast material (300 mgI/ml or 350 mgI/ml) flushed with 50 ml of
      saline solution at a rate of 5 ml/sec. The saline flush technique demonstrated
      statistically significantly greater portal enhancement. Therefore, we consider
      that this technique contributes to the visualization of three-dimensional CT
      portography.

PMID- 14587412
TI  - [Three-dimensional fusion imaging of lymphoscintigraphy and MDCT for sentinel
      node biopsy in breast cancer].
AB  - The purpose of this study was to evaluate the clinical usefulness of three
      dimensional (3D) fusion imaging of lymphoscintigraphy with 99mTc phytate and MDCT
      (four-slice CT) for sentinel node biopsy in breast cancer. Volume-rendering
      images generated by MDCT were fused with lymphoscintigrams on a personal
      computer. The subjects were 7 patients with clinically negative nodes. In all
      patients, sentinel nodes were identified by lymphoscintigraphy, and the
      anatomical locations of sentinel nodes were clearly demonstrated by 3D-fusion
      imaging. 3D-fusion imaging of lymphoscintigraphy and MDCT is expected to be a
      promising method for sentinel node biopsy in breast cancer.

PMID- 14587413
TI  - [Three-dimensional angiography of arteries and veins around the stomach using
      multislice CT for preoperative simulation of laparoscopic gastric cancer surgery:
      trial of multiphase fusion method].
AB  - Postcontrast CT scanning using multislice CT was performed for 20 patients with
      gastric cancer. Three-dimensional (3D) CT angiography of the arterial and venous
      phases was reconstructed using the volume-rendering technique and then fused. 3D
      CT angiography showed the arteries and veins around the stomach, and multiphase
      fusion imaging was able to demonstrate clearly and three-dimensionally the
      gastric vascular anatomy. In conclusion, the multiphase fusion image was
      considered to be useful in the preoperative simulation of laparoscopic gastric
      cancer surgery.

PMID- 14587414
TI  - [A case of ovarian cystadenofibroma with papillary projections showing very high
      signal intensity on T2-weighted images].
AB  - Cystadenofibromas are rare benign or borderline malignant neoplasms containing
      both epithelial and stromal components. We report a case of endometrioid
      cystadenofibroma in a patient with endometriosis. In this case, the solid
      component showed very high signal intensity on T2-weighted images and was
      enhanced after Gd-DTPA administration, reflecting marked stromal edema of fibrous
      tissue. Endometrial cysts with malignant transformation are reported to have an
      enhancing solid component and to show various intensities on T2-weighted imaging.
      However, a solid component showing very high signal intensity on T2-weighted
      images should also be considered stromal edema in benign or borderline
      cystadenofibromas.

PMID- 14587415
TI  - [Two cases of radiation myositis probably induced by recall phenomenon].
AB  - Two cases of radiation myositis following gemcitabine-based chemotherapy for
      advanced non-small cell lung cancer are presented. In the two cases, myositis
      appeared 3 and 5.5 months after the completion of radiation therapy and 2 and 2.5
      months after the beginning of chemotherapy, respectively. The affected areas, the
      upper back and right thigh, appeared as areas of increased signal intensity on T2
      weighted MR imaging and were enhanced by the administration of Gd-DTPA in the
      skeletal muscles. These coincided with the previously irradiated area. Although
      radiation myositis is a rare complication, it is important to be careful of
      radiation recall induced by chemotherapeutic agents.

PMID- 14587416
TI  - [Severe acute respiratory syndrome].

PMID- 14587417
TI  - [Quality of life assessment in patients with non-small cell lung cancer treated
      surgically or with pre-operative chemotherapy followed by surgery].
AB  - The aim of the study was assessment of quality of life (QL) in patients with non
      small cell lung cancer treated surgically or treated with both: neoadjuvant
      chemotherapy and surgery. We evaluated 200 NSCLC patients in I-IIIa stages. They
      were divided into 2 groups. Group 1-136 surgical only patients, group 2-64
      patients treated with pre-operative chemotherapy, followed by surgery. Some of
      the patients from both groups required postoperative chemotherapy or
      radiotherapy. We used QLQ-C30 and QLQ-LC13 questionnaires both made and used with
      permission of EORTC. Measurements were taken while patients were qualified for
      treatment, 10-15 days after surgery and 4 and 12 months after treatment.
      Additional measurements were taken after pre-operative chemotherapy in group 2.
      Global QL (noted during qualification for treatment) decreased significantly in
      early postoperative period, regardless the range of resection in both groups.
      There were also significant decrease in functioning, increase in disease symptoms
      and financial difficulties after operation. In course of time all parameters of
      QL were stabilised and after the year they were higher than before treatment. Pre
      operative chemotherapy and post-operative radiotherapy had no significant
      influence on QL. This was observed among the patients treated with post-operative
      chemotherapy. The assessment of QL seems to be a more effective method of
      treatment evaluation, because it allows seeing the patient as a part of the
      society in which he is living.

PMID- 14587418
TI  - [Value of electrocardiography in the diagnosis of acute pulmonary embolism].
AB  - Diagnosis of acute pulmonary embolism is difficult. The aim of the study was
      analysis of electrocardiographic (ECG) changes in patients with acute pulmonary
      embolism and analysis of correlations between electrocardiographic changes and
      pulmonary angiography and pulmonary artery pressure. ECG in 22 patients aged 47
      +/- 13 years old (9 women and 13 men) with confirmed pulmonary embolism and
      without pre-existing cardiorespiratory diseases were analyzed. Most frequently
      tachycardia, negative T wave in III, aVF and precordial leads, dextrogyria and
      dextrogram in ECG were observed. In 20 patients 3 or more criteria were found.
      Index Milleri--an quantitative method of estimation of pulmonary embolism
      correlated with pulmonary artery pressure. Conclusion of this study is that ECG
      is one of the important diagnostic tests in patients with pulmonary embolism: it
      gives us information about changes in pulmonary arteries.

PMID- 14587419
TI  - [Prognosis in limited disease (LD) small cell lung cancer (SCLC) patients
      according to status performance, local extension of lesions, type of treatment
      and the completeness of staging].
AB  - The aim of this study was to assess the prognosis in LD SCLC pts according to
      their performance status, local extension of lesions, type of treatment and the
      completeness of staging. In the period 01.01.1986-31.12.1996 in the Institute of
      Tuberculosis and Chest Diseases 579 consecutive SCLC pts were treated. LD was
      diagnosed in 345 pts. In 193 out of them the staging was complete that is in
      addition to chest x-ray, abdomen USG/CT, brain CT/MRI and bilateral bone marrow
      trepanobiopsy was done. 152 pts were also regarded as limited but the staging was
      not complete. LD pts proved by complete staging survived significantly longer
      (median survival 15.7 months) than others (median survival 10.2 months). The pts
      in whom complete staging was done were however in better performance status and
      had smaller local extension of lesions and had more often radiotherapy than
      others. Status performance, local extension of lesions and radiotherapy but also
      completeness of staging were independent prognostic factors in multivariate
      analysis.

PMID- 14587420
TI  - [Smoking cessation program based on pharmacological support (bupropion SR). Our
      own experience].
AB  - Smoking constitutes the gravest, yet avoidable, deadly threat to health in
      Poland. Near the end of the 90-ies it was discovered that the antidepressant 
      bupropion- has positive effects in the treatment of addiction to nicotine. The
      aim of the study was the evaluation of the efficacy of ambulatory, intensive
      smoking cessation program based on bupropion SR with educational support. 54
      smokers (18 men and 36 women) were enrolled, age 22-59 yr. (mean 45.5 +/- 8.7),
      smoking 10-50 cigarettes daily. Early abstinence rate (7 weeks after quitting)
      was 61.1%, after 6 months 45.2% of the participants were still non-smokers. The
      most common adverse effects of bupropion SR therapy were mouth dryness and sleep
      disturbances, 13% of patients had to stop using bupropion because of side
      effects. High percentage of abstinence indicates that intensive smoking cessation
      programs should be used as a part of antinicotine strategy. The pharmacological
      support in the nicotine dependence treatment should be performed under careful
      physician supervision.

PMID- 14587421
TI  - [Influence of orthopnoea position on spirometric and plethysmographic parameters
      in patients with chronic obstructive pulmonary disease ].
AB  - Chronic obstructive pulmonary disease (COPD) is characterized by the lack or only
      slight reversibility of obstruction which can be assessed by spirometry after
      inhalation of short-acting beta 2-mimetic (e.g. Salbutamol). The aim of the study
      was to determine if subjective decrease in dyspnoea sensation notified by COPD
      patients in orthopnoea position is reflected in spirometry and plethysmography.
      The study was carried out in the group of 30 patients with COPD (FEV1 = 30-70% of
      predicted value) as well as in 30 sex- and age-matched non-smoking healthy
      subjects. We observed the increase of spirometric parameters (FEV1, FEV1%VC,
      FEF75, PEF) and the decrease of plethysmographic parameters (RTOT, RV, RV%TLC)
      after the change from the initial to orthopnoea position (p < 0.001). The
      obtained results show that orthopnoea position leads to the decline of
      obstruction degree, pulmonary hyperinflation and the decrease of dyspnoea
      sensation.

PMID- 14587422
TI  - [Comparison of answers to a sleep questionnaire of middle-age adults in Warsaw].
AB  - In 1997 we evaluated answers to a sleep questionnaire in a representative sample
      of 1186 persons of adult population of Warsaw. In the year 2000 we sent the same
      questionnaire to all persons who participated in the 1997 investigations. 676
      (57%) subjects responded. There were 53% males and 47% females in the studied
      group. Their mean age was 56.6 +/- 8 years. There was no difference in age and
      sex between responders and non-responders. The standardized questionnaire
      contained questions assessing the following items: snoring, excessive daytime
      sleepiness, apnoeas observed by the sleep partner, sleep time and sleep latency.
      During a 3-year follow-up mean sleep time on working days did not change and
      remained 7.1 +/- 1.1 h. However, the subjects slept significantly shorter time at
      weekends, 8.1 +/- 1.3 and 7.9 +/- 1.3 h respectively (p < 0.001). There was a
      decrease in percentage of snorers from 81% to 75% and increase in BMI from 27 +/-
      4.5 to 29 +/- 5 kg/m2. The daytime sleepiness was reduced from 7.9 +/- 4.5 to 6.4
      +/- 3.9 points (p < 0.001).

PMID- 14587423
TI  - [Eosinophilic myocarditis in allergic angiitis and granulomatosis (Churg-Strauss
      syndrome) ].
AB  - Allergic angiitis and granulomatosis (Churg-Strauss syndrome) is one of the rare
      form of idiopathic (primary) vasculitis. It is characterized by asthma, blood
      hypereosinophilia and typical microscopic features: nectrotizing vasculitis,
      tissue infiltration by eosinophils and extravasal granulomas. We present an
      autopsy case of 55-years old man with Churg-Strauss syndrome complicated by
      eosinophilic myocarditis.

PMID- 14587424
TI  - [Pathophysiology of malignant pleural effusions].

PMID- 14587425
TI  - [Diagnosis of malignant pleural effusion].

PMID- 14587426
TI  - [Treatment of malignant pleural effusion].

PMID- 14587428
TI  - [Assessment of cough threshold in patients with gastroesophageal reflux disease].
AB  - The aim of this study was the assessment of citric acid cough threshold in
      patients with chronic cough due to GERD, confirmed by 24-hour esophageal pH-
      monitoring, with other reasons of chronic cough excluded. Thirty subjects with
      chronic cough due to GERD and 15 healthy volunteers underwent cough challenge
      with doubling concentrations of citric acid using Asthma Provocation System
      (Jaeger). The cough threshold was defined as the first concentration of citric
      acid that induced cough. Spirometric parameters (FEV, PEF and FVC) were measured
      before and 10 minutes after cough challenge in all groups. A day and night cough
      score diaries (verbal category descriptive score) were completed in all subjects.
      The cough threshold was significantly lower in GERD patients in comparison with
      healthy volunteers. In GERD patients the negative correlation was found between
      day cough score measurements and cough threshold. Citric acid cough challenge did
      not cause bronchoconstriction or any significant change of spirometric
      parameters.

PMID- 14587427
TI  - [Sleep and breathing at altitude of 3800 m--the acclimatization effect].
AB  - Periodic breathing (PB) is a very common phenomenon occurring during sleep at
      high altitude. It consists of repetitive apneas or hypopneas of central origin
      and clusters of hyperpneic breaths. The aim of this study was to analyze sleep
      structure and periodic breathing in shift workers of a gold mine situated in Tien
      Schan Mountains at 3800 m. In 12 subjects aged 36.1 +/- 9.3 yrs, polysomnography
      (PSG) was performed twice, on the night after the first working shift or during
      the day following first night shift, and the second PSG at the end of the first
      week of work. After one week, significant increase in REM sleep was noticed (5.2
      +/- 4.0% vs. 12.0 +/- 6.7%, p < 0.05). There were no differences in sleep pattern
      between night sleep and sleep during daytime. During first PSG periodic breathing
      was seen in all subjects and occupied 14.7 +/- 16.6% of total sleep time. After
      one week PB decreased in 8 subjects however, in 4 subjects an increase in PB was
      observed (15.4 +/- 11.2 vs. 29.0 +/- 11.8% of sleep time). CONCLUSIONS: Sleep at
      altitude is characterized by reduction of REM sleep, which improves after a week
      of acclimatization. There are great individual variations in duration of periodic
      breathing; in some subjects an increase in PB can be seen.

PMID- 14587429
TI  - [Effect of IFN-gamma on IGE dependent leukotriene generation by peripheral blood
      leukocytes in patients with chronic allergic rhinitis in vitro].
AB  - Interferon gamma (IFN-gamma) is a cytokine characterized by different biologic
      and immunologic activities. Leukotrienes are proinflammatory mediators released
      both in immediate and late allergic reactions. These facts suggest that
      leukotrienes and IFN-gamma might cooperate in allergic inflammation. The aim of
      this study was to investigate the influence of IFN-gamma on leukotriene C4 (LTC4)
      production by peripheral blood leukocytes isolated from the patients suffering
      from perennial allergic rhinitis caused by allergy to mites. Eleven patients
      entered the study. LTC4 released from leukocytes stimulated by Dermatophagoides
      pteronyssinus allergen alone, and after preincubation with IL-3 was examined. The
      influence of preincubation of leukocytes with IFN-gamma in concentrations of 1,10
      and 100 ng/ml on mentioned allergen stimulation procedures was also investigated.
      The concentration of LTC4 in supernatants was measured by CAST-ELISA method. The
      difference between concentration of LTC4 released in medium with and without IL-3
      represented the effect of priming. We observed that IFN-gamma suppressed release
      of LTC4 only from leukocytes incubated with IL-3 in dose-dependent fashion. On
      the basis of these data we can postulate that IFN-gamma inhibits IL-3 dependent
      cell priming, but has no influence on LTC4 secretion per se.

PMID- 14587430
TI  - [Analysis of possible causes of recurrent respiratory tract infections in
      children from Lodz, Poland].
AB  - Recurrent respiratory tract infections are responsible for about 85% of all
      diseases in childhood. Early diagnosis helps to prevent infections and start the
      appropriate treatment, what in turn prevents lungs from irreversible damage. The
      aim of this study was the analysis of possible causes of recurrent respiratory
      tract infections in children in Lodz region. We analyzed cases of 6335 children
      with recurrent respiratory tract infections, age 3 months to 17 years, referred
      to the clinic in our hospital by family doctors from 2000 to 2002. Among all
      children, 41.5% were diagnosed with allergy, 26.9% of patients had persistent
      Mycoplasma pneumoniae and 1.4% Bordetella pertussis infection. Very disturbing
      was the fact of very late cystic fibrosis diagnose at the age of 7,11 and 16.
      Congenital immune disorders were diagnosed late in five children at the age of
      6,7,8,9,11, what delayed appropriate therapy and early prevention of infections.

PMID- 14587431
TI  - [Pulmonary tuberculosis after 11 years of observation in a patient suffering from
      advanced squamous lung cancer cured by radical radiotherapy--a case report].
AB  - Advanced lung cancer is a neoplasm of a poor prognosis. The treatment may improve
      it to a certain degree but not satisfactory. A case of squamous- cell lung
      cancer, in a stage III B of TNM classification, which was by cured completely
      radiotherapy is described. The 11 years post-treatment observation was performed
      without any symptoms of recurrence. Actually patient is hospitalised due to
      active tuberculosis. No evidence for lung cancer was found until now.

PMID- 14587432
TI  - [Mydocalm causing anaphylaxis].
AB  - The case of anaphylactic shock due to Mydocalm administration is presented. 49
      year-old woman suffered from spinal osteoarthritis and she was treated with
      NSAIDs and Mydocalm for many years. 6 weeks before admission to hospital the
      first anaphylactic shock was developed with loss of consciousness after oral
      administration of Mydocalm. Then she was admitted to the hospital in order to
      diagnose and verify the suspicion whether Mydocalm caused this reaction.
      Percutaneous test with Mydocalm was performed and it caused anaphylactic shock.
      Only thirteen cases like this one have been documented in the world literature.
      It is the first case reported in Poland.

PMID- 14587434
TI  - [SARS--severe acute respiratory syndrome--current knowledge].

PMID- 14587433
TI  - [Sepsis with staphylococcal vegetation on tricuspid valve. Differential diagnosis
      with Wegener's granulomatosis].
AB  - Acute, febrile disease in a young person with no previous medical history is most
      often caused by infection. If disease progresses despite antimicrobial treatment
      vascular and collagen diseases should be taken into account in differential
      diagnosis We present a case of a young man, with lung infiltrations and cavities
      in the course of febrile illness. He was referred to our hospital with a
      suspicion of Wegener's granulomatosis after few days of ineffective antimicrobial
      therapy. Positive blood culture for S. aureus and demonstration of tricuspid
      valve vegetation on echocardiographic examination enabled to make a final
      diagnosis of infective endocarditis with multiple lung abscessus.

PMID- 14587435
TI  - [PEF measurements in diagnosis and monitoring of bronchial asthma].

PMID- 14587436
TI  - [Mechanisms regulating tissue eosinophilia in bronchial asthma: focus on
      apoptosis].

PMID- 14587437
TI  - [Airway remodeling in asthma].
AB  - Asthma is a chronic inflammatory disease of the airways in which many cell types
      play a role. These cells are involved in the regulation of the airways
      inflammation and initiate the process of remodelling by the release of cytokines
      and growth factors. In the article the authors describe changes in airways wall
      in asthmatic patients and their clinical consequences.

PMID- 14587438
TI  - [The production of pharmaceuticals in the world will become polarized].

PMID- 14587439
TI  - [Osteoporosis--a new challenge for pediatricians].

PMID- 14587440
TI  - [What have we learned about the coronaviruses in animals?].

PMID- 14587441
TI  - [Tuberculosis in Finland].

PMID- 14587442
TI  - [Malarias in Finland-- experiences and findings during three decades].

PMID- 14587443
TI  - [Iodine deficiency exists in many European countries but not in Finland].

PMID- 14587444
TI  - [Magnetoencephalography as a tool for a clinician].

PMID- 14587445
TI  - [Are the diseases of adulthood determined already during fetal period and
      childhood?].

PMID- 14587446
TI  - [Familial carpal tunnel syndrome--a more common syndrome than anticipated].

PMID- 14587447
TI  - [Why does a man have bruises after sawing wood in order to warm up the sauna?].

PMID- 14587448
TI  - [Syphilis behind the mouth symptoms].

PMID- 14587449
TI  - [Sudden edema and pain in the knee].

PMID- 14587450
TI  - [Juho Makela: boys sitting on a fence near the water].

PMID- 14587451
TI  - [Pharmaca Fennica and the information about parallel pharmaceutical derivatives].

PMID- 14587452
TI  - [It is worth studying the mortality].

PMID- 14587453
TI  - [Prostate cancer].

PMID- 14587454
TI  - [C-reactive protein--the most important risk factors of atherosclerosis?].

PMID- 14587455
TI  - [What new about the common cold?].

PMID- 14587456
TI  - [Why is peritoneal dialysis used more in Finland?].

PMID- 14587458
TI  - [Thrombolytic therapy of cerebral infarction using alteplase--the Helsinki
      model].

PMID- 14587459
TI  - [Organizing the thrombolytic therapy of cerebral infarction in Lapland].

PMID- 14587460
TI  - [Peritonitis as a complication of peritoneal dialysis--experiences during 23
      years at Oulu University Hospital].

PMID- 14587461
TI  - [Inflammatory myofibroblastic tumor--benign or malign?].

PMID- 14587462
TI  - [How to prevent conduct disorders in adolescents?].

PMID- 14587463
TI  - [What are good statistical graphics made of?].

PMID- 14587464
TI  - [EEG findings in post-ischemic myoclonus].

PMID- 14587465
TI  - [Abdominal pain in a refugee].

PMID- 14587466
TI  - [A prolonged gastroenteritis].

PMID- 14587467
TI  - Role for endocytosis in conjugation in Tetrahymena.
AB  - We examined the effect of inhibitors of receptor-mediated endocytosis on cell
      pair formation during conjugation in Tetrahymena thermophila. Dansylcadaverine
      (20 microM), methylamine (20 mM), and bacitracin (2 mg/ml) prevented cell pair
      formation even when added poststarvation, after mixing of cells of opposite
      mating types (during the preparing interaction). Chloroquine (10 and 25 microM)
      did not inhibit cell pair formation, leading to the conclusion that inhibition by
      dansylcadaverine, methylamine, and bacitracin is not due to an alkalinization of
      the lysosome. These results did not allow us to define the time in the preparing
      interaction at which inhibition occurs, nor to identify the cellular components
      involved, but they did support the hypothesis that an endocytotic event(s) plays
      a role in the cell contact-mediated recognition which occurs during the preparing
      interaction.

PMID- 14587469
TI  - [West Nile virus also in the Netherlands??].

PMID- 14587468
TI  - Pneumococcal immunization of hospitalized patients.

PMID- 14587470
TI  - Abstracts of the Joint Meeting of the British Association of Head and Neck
      Oncologists and the British Association of Head and Neck Oncology Nurses. May 9,
      2003. London, United Kingdom.

PMID- 14587471
TI  - Educational and abstract book of the European Society for Medical Oncology (ESMO)
      Summer Educational Conference. June 19-22, 2003. Edinburgh, Scotland, United
      Kingdom.

PMID- 14587472
TI  - Proceedings of the Clinical Investigators Update Meeting on Gastrointestinal
      Cancer. April 20, 2002. Cagliari, Italy.

PMID- 14587473
TI  - Proceedings of the Moo-Young Symposium on Biotechnology and Bioengineering.
      Waterloo, Ontario, Canada. September 6-7, 2002.

PMID- 14587474
TI  - Medical image. Mediastinal pseudo-mass.

PMID- 14587475
TI  - Healthcare assistants should be registered.

PMID- 14587476
TI  - Medical discipline--not guilty.

PMID- 14587477
TI  - Disgraceful conduct--unsafe practice.

PMID- 14587478
TI  - Healthcare assistants should be registered.

PMID- 14587479
TI  - Nursing profession must unite to survive.

PMID- 14587480
TI  - Are you my parent? Are you my child? The role of genetics and race in defining
      relationships after reproductive technological mistakes.

PMID- 14587481
TI  - Boutique egg donations: a new form of racism and patriarchy.

PMID- 14587482
TI  - Life: defining the beginning by the end.

PMID- 14587483
TI  - The ethics of mandatory HIV testing of all pregnant women.

PMID- 14587484
TI  - A historical perspective of casuistry and its application to contemporary
      biomedical ethics.

PMID- 14587485
TI  - Which medical ethics for the 21st century?

PMID- 14587486
TI  - The arguments for euthanasia and physician-assisted suicide: Catholic response.

PMID- 14587487
TI  - For whose eyes only: how do you preserve scientific freedom and combat terrorism?

PMID- 14587488
TI  - Recipes for bioterror: can we stop potentially deadly biotech research getting
      into the wrong hands?

PMID- 14587489
TI  - Researchers' links with biomed industry lead to bias in clinical trials.

PMID- 14587490
TI  - Johnny Mnemonic's headache.

PMID- 14587491
TI  - The world's first brain prosthesis.

PMID- 14587492
TI  - Madness on trial.

PMID- 14587493
TI  - Rein in the extremists.

PMID- 14587494
TI  - Variations on a theme: just because creatures share the same genes doesn't make
      them identical.

PMID- 14587497
TI  - Antimicrobial agents in periodontal prevention, therapy and maintenance.
      Proceedings of  the GABA Forum. December 6, 2002. Lyon, France.

PMID- 14587496
TI  - Update on rivastigmine.
AB  - BACKGROUND: Rivastigmine is a carbamate drug designed to inhibit both
      acetylcholinesterase and butyrylcholinesterase by reversibly covalently bonding
      to these enzymes. Butyrylcholinesterase in-creases as Alzheimer disease
      progresses, so its inhibition may become more important as the disease worsens.
      Metabolism of rivastigmine occurs at the synapse rather than at the liver and
      previous studies have demonstrated no drug-drug interactions. Rivastigmine has a
      half-life at the synapse of 9 hours allowing for bid dosing. REVIEW SUMMARY:
      Effective therapy requires up-titration from initial dosage of 3 mg/d to 6 mg/d
      with additional increases to 9 mg or 12 mg/d giving additional benefits in some
      patients. Beneficial effects with rivastigmine therapy in the functioning of
      activities of daily living, behavior, cognition, and global functioning have been
      demonstrated in patients with mild to moderate Alzheimer disease in 4 large
      double-blind, placebo-controlled multicenter clinical trials. Potential adverse
      effects of nausea, vomiting, or diarrhea in these original Alzheimer trials with
      rapid (every week) dosage increases occurred in up to 34% of patients and can be
      minimized by slower monthly up-titrations. Rivastigmine also was proven effective
      in decreasing psychiatric symptoms and cognitive deficits in a large double
      blind, placebo-controlled trial in patients with diffuse Lewy body disease. Other
      studies have suggested that rivastigmine improves symptoms in nursing home
      patients with more severe stage Alzheimer disease, Parkinson dementia, and
      subcortical dementia. Follow-up studies have suggested that rivastigmine may
      delay disease progression and, in patients discontinuing the drug, no withdrawal
      effects were seen. CONCLUSION: Rivastigmine is an effective therapeutic agent for
      treating cognitive and behavioral symptoms in Alzheimer disease and diffuse Lewy
      body disease and may also have beneficial effects in vascular and Parkinson
      dementias.

PMID- 14587498
TI  - Proceedings of the 13th International Symposium on Capillary Electroseparation
      Techniques. September 1-4, 2002. Helsinki, Finland.

PMID- 14587499
TI  - Abstracts of the Canadian Cardiovascular Congress 2003 held jointly with the XIX
      InterAmerican Congress of Cardiology and the 56th annual meeting of the Canadian
      Cardiovascular Society. October 24-29, 2003, Toronto, Canada.

PMID- 14587500
TI  - ASRM 2003. Abstracts of the 59th annual meeting of the American Society for
      Reproductive Medicine. October 11-15, 2003. San Antonio, Texas, USA.

PMID- 14587501
TI  - Proceedings of a general discussion on quantum inorganic chemistry. York, United
      Kingdom, April 15-16, 2003.

PMID- 14587502
TI  - The BJOG (British Journal of Obstetrics and Gynaecology) celebrates its
      centenary.

PMID- 14587503
TI  - Patient outcomes in rheumatology. A review of measures.

PMID- 14587504
TI  - Abstracts of the XXXIst Meeting of the International Society for
      Oncodevelopmental Biology and Medicine, ISOBM 2003. August 30-September 4, 2003,
      Edinburgh, United Kingdom.

PMID- 14587505
TI  - [Pneumology in the year 2002].

PMID- 14587506
TI  - Proceedings of the Canadian National Immunization Conference. December 1-3, 2002.
      Victoria, British Columbia, Canada.

PMID- 14587507
TI  - Abstracts of the IX National Congress of the Italian Federation of Digestive
      Disease. Florence, Italy, 22-26 February 2003.

PMID- 14587508
TI  - Abstracts of the British Pharmacological Society Meeting. 25-27 June 2003,
      University of Surrey, Guildford.

PMID- 14587509
TI  - JFR' 2003 book of abstracts. 51st French Radiology Meeting and 24th Francophone
      Meeting organized by the French Society of Radiology. Paris, France, 18-22
      October 2003.

PMID- 14587510
TI  - [Abstracts of the 45th National Congress of Anesthesia and Resuscitation. Paris,
      France, 18-21 September 2003].

PMID- 14587511
TI  - Proceedings of the XXVIII Congress of the Society of Biomechanics. Poitiers,
      France, 11-12 September 2003.

PMID- 14587512
TI  - Abstracts of the 3rd European Academy of Forensic Science Meeting. September 22
      27, 2003. Istanbul, Turkey.

PMID- 14587513
TI  - Abstracts of the XXII Annual European Society of Regional Anaesthesia Congress.
      Malta, 2003.

PMID- 14587514
TI  - Abstracts of the 10th International Conference on Human Antibodies and
      Hybridomas. 8-10 October 2003, Osaka, Japan.

PMID- 14587515
TI  - Current awareness on yeast.

PMID- 14587516
TI  - [Consensus Conference on Chronic Obstructive Pulmonary Disease. Madrid, Spain, 25
      26 November 2002. Proceedings].

PMID- 14587517
TI  - Abstracts of the 5th International Symposium of NeuroVirology. HIV Molecular and
      Clinical Neuroscience Workshop. 2-6 September 2003, Baltimore, Maryland, USA.

PMID- 14587518
TI  - Abstracts of the 34th Annual Meeting of the German Society of Immunology and the
      3rd Meeting of the European Mucosal Immunology Group. September 24-28, 2003.
      Berlin, Germany.

PMID- 14587519
TI  - Single-molecule visualization in cell biology.
AB  - Recent progress in single-molecule detection techniques has allowed us to
      visualize the dynamic behaviour and reaction kinetics of individual biological
      molecules inside living cells. Single-molecule visualization provides a direct
      way to quantify, with a high spatial and temporal resolution, biological events
      inside cells at the single-molecule level. In this article, we discuss how single
      molecule visualization can be used in cell biology.

PMID- 14587520
TI  - Electron microscopy in cell biology: integrating structure and function.
AB  - Electron microscopy (EM) is at the highest-resolution limit of a spectrum of
      complementary morphological techniques. When combined with molecular detection
      methods, EM is the only technique with sufficient resolution to localize proteins
      to small membrane subdomains in the context of the cell. Recent procedural and
      technical developments have increasingly improved the power of EM as a cell
      biological tool.

PMID- 14587521
TI  - MRI: volumetric imaging for vital imaging and atlas construction.

PMID- 14587522
TI  - Imagining imaging's future.
AB  - Imaging specific molecules and their interactions in space and time will be
      essential to understand how genomes create cells, how cells constitute organisms
      and how errant cells cause disease. Molecular imaging must be extended and
      applied from nanometre to metre scales and from milliseconds to days. This quest
      will require input from physics, chemistry, and the genetics and biochemistry of
      diverse organisms with useful talents.

PMID- 14587523
TI  - [Abstracts of the XXXIII Congress of the Spanish Society of Nephrology. Palma de
      Mallorca, Spain, 12-15 October 2003].

PMID- 14587524
TI  - Abstracts of the American Association for Cancer Education 37th annual meeting.
      October 30-November 2, 2003. Little Rock, Arkansas, USA.

PMID- 14587526
TI  - Osteoarthritis Research Society International (OARSI) list of members.

PMID- 14587525
TI  - Abstracts of the 8th World Congress of the Osteoarthritis Research Society
      International (OARSI). Berlin, Germany, 12-15 October 2003.

PMID- 14587527
TI  - Medical devices; immunology and microbiology devices; classification of the West
      Nile Virus IgM capture Elisa assay. Final rule.
AB  - The Food and Drug Administration (FDA) is classifying the West Nile Virus IgM
      Capture Elisa assay into class II (special controls). The agency is taking this
      action in response to a petition submitted under the Federal Food, Drug, and
      Cosmetic Act (the act) as amended by the Medical Device Amendments of 1976 (the
      amendments), the Safe Medical Devices Act of 1990, and the Food and Drug
      Administration Modernization Act of 1997 (FDAMA). The agency is classifying this
      device into class II (special controls) in order to provide a reasonable
      assurance of safety and effectiveness of the device. Elsewhere in this issue of
      the Federal Register, FDA is announcing the availability of a guidance document
      that will serve as the special control for the device.

PMID- 14587528
TI  - Educational attainment, positive psychological mediators, and resources for
      health and vitality in older adults.
AB  - OBJECTIVES: To further explain the relationship of education to health by a
      prospective examination of positive psychological states as mediators.
      Furthermore, to examine the resources of desirable events, self-esteem, and
      social support as possible mediators between positive psychological states and
      subsequent health and vitality. METHODS: Four in-home interviews were conducted
      at 6-month intervals with a probability sample of 1,277 older adults (aged 55 and
      older); multiple regression was used to estimate mediating effects. RESULTS:
      Positive states mediated the education relationship to both symptoms and
      vitality, independent of negative states; the resource measures did not mediate
      the positive state-health relationship. DISCUSSION: Higher education level
      appears to increase the likelihood of being serene and happy, and healthy and
      vital, in later years; positive psychological states appeared to have both a
      promotion function (for vitality) and protective function (against health
      symptoms); self-esteem showed promise as a possible mediator of the effects of
      psychological states on health.

PMID- 14587529
TI  - Social ties and perceived support: two dimensions of social relationships and
      health among the elderly in Taiwan.
AB  - OBJECTIVES: Assess the effects of social relationships on physical and mental
      health among the elderly in Taiwan. METHODS: Using 4 waves of a survey of the
      elderly, we examine the relationship between social ties and perceived support
      and four health outcomes--mortality, functional status, self-assessed health, and
      depression. RESULTS: Perceived support and social ties are related to health, but
      many of the apparent effects are attenuated in the presence of controls for prior
      health. However, positive perceptions about support are protective of mental (but
      not physical) health. DISCUSSION: If baseline health is ignored, estimates of the
      effects of social relationships on health at a given stage of life are likely to
      be inflated by reverse causality or by effects occurring prior to baseline.
      Inclusion of controls for initial health reveals that, in general, the
      relationship between social support and health at the older ages in Taiwan is
      relatively modest.

PMID- 14587530
TI  - [Lacidipine: a new third generation calcium channel blocker].

PMID- 14587531
TI  - Molecular events associated with dendritic cells activation by contact
      sensitizers.
AB  - Dendritic cells are unique heterogenous cell population capable of responding to
      different inflammatory signals. These signals induce the process of maturation
      forcing cells to leave the inflamed site and to migrate to draining lymph nodes.
      During this process, dendritic cells have to initiate differentiation responses
      expressed among others by up-regulation of some surface antigens (e.g., MHC or
      costimulatory molecules) and down-regulation of the others (e.g., E-cadherin).
      There are more and more data published indicating that chemical compounds known
      to initiate contact hypersensitivity (haptens) can also induce the process of
      dendritic cells maturation resembling in some aspects their maturation after
      contact with common inflammatory factors. Although molecular events associated
      with the process have not yet been dearly defined, there is growing evidence that
      haptens mediate activation of dendritic cells by activating mitogen-activated
      protein kinases, mainly p38 MAPK. It may be speculated that further downstream
      signals include activation of transcription factors such as nuclear factor kappa
      B (NF-kappaB), activating transcription factor-2 (ATF-2) or cAMP response element
      binding protein (CREB). The present review will focus on some aspects of signal
      transduction pathways in dendritic cells stimulated with contact sensitizers.

PMID- 14587532
TI  - No effects of acute exposure to the electromagnetic field emitted by mobile
      phones on brainstem auditory potentials in young volunteers.
AB  - OBJECTIVES: A widespread use of mobile phones evokes a growing concern for their
      possible adverse effects on the human central nervous system. This study was
      aimed at evaluating the effects of EMF generated by mobile phones, at all
      standard wavelengths: 450, 935 and 1800 MHz used in Poland, on the auditory
      brainstem-evoked responses (ABR) during and after the exposure. MATERIALS AND
      METHODS: The effects of acute exposure to electromagnetic fields (EMF) on ABR
      were evaluated in 45 young, healthy volunteers of both genders. The
      electromagnetic impulses were generated with the antenna of mobile phone. The
      exposure was induced by repeated phone activation for 20 min. The ABR evaluation
      was performed before, during and immediately after the exposure, and the
      latencies of waves I, III and V, and inter-waves I-V were analyzed. RESULTS:
      Prior test calibration on a phantom did not show the influence of the external
      EMF generated by the mobile phone on the ABR equipment. For neither EMF
      frequency, differences were observed in wave and inter-wave latencies during and
      after exposure to EMF compared to the initial ABR pattern, in both men and woman.
      CONCLUSIONS: This implies that commonly used mobile phones do not affect
      propagation of electrical stimuli along the auditory nerve to auditory brainstem
      centers.

PMID- 14587534
TI  - Study of extremely low frequency electromagnetic fields in infant incubators.
AB  - OBJECTIVES: The aim of the work was to present the results of measurements of
      extremely low frequency electromagnetic fields (ELF EMF), namely the magnetic
      flux density, inside infant incubators, and to compare these results with the
      data published by other authors who point out to a possible association between
      leukemia or other diseases observed in newborns kept in incubators after the
      birth and the ELF EMF exposure in the incubator. The measured magnetic flux
      densities were compared with the reference values for this frequency range
      indicated in the European Union (EU) recommendations. MATERIALS AND METHODS: The
      repeated measurements in incubators were made with a calibrated magnetometer EFA
      300 in the frequency range of 5-30 kHz. Effective values of magnetic flux
      densities of ELF EMF were determined taking account of the reference values.
      RESULTS: The results of many repeated measurements showing the values of magnetic
      flux density in modern incubators with plastic supporting frame, were compared
      with those obtained in old type incubators with iron skeleton. A power frequency
      of 50 Hz was detected in the incubator and the ELF EMF values were by over two
      orders lower than the EU reference values. CONCLUSIONS: The paper emphasizes the
      need to take a special care of newborns kept in incubators even if only the sub
      reference values are detected. The EU reference values are intended for the adult
      human population. A baby in an incubator has much smaller dimensions, higher
      electric conductivity and maybe trigger another mechanism of response to ELF EMF
      than that indicated in this paper.

PMID- 14587533
TI  - Assessment of lung particle accumulation in factory workers by magnetic field
      measurement.
AB  - OBJECTIVES: In industrial settings, minute particles of industrial substances
      lodge in the lungs and accumulate over decades, often leading to pneumoconiosis.
      Although these particles have been almost impossible to detect with x-rays,
      especially initially, we still rely upon them for detection of such deposits. As
      a result, particle accumulation is not detected early enough, and eventually
      diagnosed pneumoconiosis is typically irreversible. Accordingly, we investigated
      an alternative detection method that utilizes the magnetic characteristics of the
      particles after they are excited by an external magnetic field. Using
      accumulation of magnetic particles as a surrogate marker for total particle
      accumulation, our goal was to develop a method that can determine particle
      quantity and distribution in the lungs of individuals in different types of
      industrial situations. This method would allow us to identify factors that affect
      particle accumulation and to detect early such accumulations, before the
      pneumoconiosis stage. The pilot study reported herein represents proof of
      principle that such a method is feasible. MATERIALS AND METHODS: After a magnetic
      field generated by a strong direct current is applied to particles, they continue
      to generate a weak magnetic field even after the external field is removed
      (relaxation). We measured relaxation using an external detector (scanning a flux
      gate magnetometer, Helmholtz coil). To field test this method. we studied 150
      subjects in various industrial settings. We studied a variety of factory workers,
      including those involved in welding and cutting for different employment
      durations. A static magnetic field of 50mT to the chest, and the residual
      magnetic field distribution were measured by scanning a flux-gate magnetometer in
      a 2-dimensional region covering the whole chest. RESULTS: The strength of the
      magnetic field from the lungs of our subjects generally increased with the length
      of employment, particularly after 11-20 years. Welders showed higher particle
      accumulation than the others. Across all types of jobs, and work durations,
      smokers had lung particle accumulations substantially higher than non-smokers.
      CONCLUSIONS: 1. In the study reported herein, we describe application of a novel,
      portable device for measuring the accumulation of magnetizable particles in the
      lungs of factory workers. These particles are viewed as a surrogate for
      determining the extent and distribution of total particles in the lung. This is
      based on the detection of signal emanating from para- and ferromagnetic particles
      when they relax after an external magnetic field is switched off. 2. Particle
      accumulation increases proportionally to employment duration in welders, but may
      be less severe in other types of workers within the same company. 3. Smoking
      greatly increases the extent of particle accumulation. 4. Additional studies are
      now necessary to correlate signal with: (a) particle density at various sites,
      (b) total particle accumulation in the lungs, (c) lung function, and (d) the
      severity of lung fibrosis and pneumoconiosis. If correlated, the method may be
      useful in the early detection of particle accumulation and may allow for the
      assessment of outcomes following interventions for the treatment and prevention
      of pneumoconiosis.

PMID- 14587535
TI  - Mould specific IgG antibodies connected with sinusitis in teachers of mould
      damaged school: a two-year follow-up study.
AB  - OBJECTIVES: The aim of this study was to describe the relationship between mould
      exposure induced by moisture damage and mould specific immunoglobulin G
      antibodies to 20 common mould species and their association with respiratory
      diseases. MATERIALS AND METHODS: Mould specific immunoglobulin G (IgG) antibodies
      were monitored in teachers in a follow-up after an extensive mould remediation
      process in school buildings. IgG antibodies to 20 different microbes were
      determined from the sera of 26 teachers (19 exposed and 7 references) by enzyme
      linked immunosorbent assay (ELISA). The serum samples were drawn twice, firstly
      at the completion of the remediation in the spring of 1997 and secondly, two
      years later in the spring of 1999. Health data was collected with self
      administered questionnaires. RESULTS: No statistical differences were found in
      the overall concentrations of 20 mould-specific IgG-antibodies between the study
      and control groups at the beginning of the study. An association between
      sinusitis and elevated mould-specific IgG-levels forAspergillus fumigatus,
      Aspergillus versicolor, Aureobasidium pullulans, Chaetomium globosum,
      Cladosporium cladosporioides, Phialophora bubakii, Rhodotorula glutinis,
      Sporobolomyces salmonicolor, Stachybotrys atra, and Tritirachium roseum was found
      in the study group. CONCLUSIONS: In a two-year follow-up the total concentration
      of the IgG antibodies for Tr. toseum was lower at the end than at the beginning
      of the follow-up and this remained significant for the group of teachers with
      sinusitis. The decrease in mould specific IgG to Cl. cladosporioides, Geotrichum
      candidum, Ph. bubakii and Rhizopus nigricans was associated with bronchitis.
      According to our knowledge, this is the first study in which the association
      between elevated mould specific IgG antibodies and sinusitis was found in the
      school environment.

PMID- 14587536
TI  - Nasal lavage fluid examination in diagnostics of occupational allergy to
      chloramine.
AB  - OBJECTIVES: Chloramine T is a known sensitising agent in the occupational
      environment of health care workers. In cases of occupational hazards induced by
      this agent, a clinical history may be far from conclusive, hence appropriate
      provocation tests are absolutely essential. The aim of the study was to evaluate
      the usefulness of the nasal challenge test in diagnostics of respiratory allergy
      to chloramine T. MATERIALS AND METHODS: A single-blind, placebo-controlled study
      was conducted in 6 subjects with chloramine T asthma and rhinitis. Two control
      groups comprised 7 atopic subjects with asthma and rhinitis and 6 healthy
      persons. All the controls had negative results of skin prick tests with
      chloramine T and none displayed any respiratory symptoms under exposure to the
      agent. A "nasal pool" technique was used to evaluate morphological and
      biochemical parameters (mast cell tryptase, eosinophil cationic protein,
      permeability index) in nasal washings before and 30 min, 4 h and 24 h after the
      provocation with chloramine T and placebo. RESULTS: A significant increase was
      found in the total count and percentage of eosinophils and basophils, albumin,
      tryptase and eosinophil cationic protein levels in the nasal lavage fluid from
      patients with chloramine T respiratory allergy when compared to both control
      groups. Also a dual asthmatic reaction in 4 patients and an isolated late
      reaction in 2 cases were observed in chloramine-sensitive subjects. CONCLUSIONS:
      The results indicate the applicability of the "nasal pool" technique as a
      diagnostic procedure in chloramine T-induced airway allergy.

PMID- 14587537
TI  - Occupational skin diseases in nurses.
AB  - OBJECTIVES: The aim of the work was to evaluate the incidence of occupational
      skin diseases in nurses, their morbidity rate, symptoms, possible causes and
      relation with occupational environment. MATERIALS AND METHODS: The study group
      consisted of 706 nurses of different hospital departments. A questionnaire and
      collection of information about the use of disinfectants were the main
      investigation methods. RESULTS: It was revealed that 47.3% nurses were suffering
      from occupational skin diseases. Allergic contact dermatitis was found to be the
      most frequent (28.5%) disease. Irritant contact dermatitis of non-allergic origin
      was diagnosed in 8.4% of nurses. The main symptoms of occupational skin diseases
      were itching and reddening. CONCLUSION: The risk of developing occupational
      dermatitis was increased by working with aldehydes and hydrogen peroxide as well
      as by using latex gloves and long working hours.

PMID- 14587538
TI  - Immunologic evaluation of hepatitis B vaccine application in hospital staff.
AB  - OBJECTIVES: The aim of our study was to assess immunological changes in hospital
      employees vaccinated five years ago with a recombinant hepatitis B vaccine.
      MATERIALS AND METHODS: 148 hospital employees were examined at different time
      periods during 5 years following a three-dose schedule of intramuscular
      immunization with a recombinant DNA hepatitis B vaccine (Engerix-B). RESULTS: At
      the end of a 5-year period, 20 vaccinees (13.5%) demonstrated a low level of HBs
      antibodies, namely < 10 mIU/ml being evaluated as lack of protection, 46 (31.1%)
      showed titers between 11 and 100 mIU/ ml corresponding to feeble protection, 54
      (36.5%) were with titers > 100 mIU/ml considered as sufficiently protected and,
      surprisingly, in 28 vaccinated persons (18.9%), titers of HBs Ab were over 1000
      mIU/ml corresponding to high protection. The HBsAg were never detected among the
      entire vaccinated group. Averaged amounts of serum immunoglobulins (IgG, IgM,
      IgA) were lower relatively to normal values only among unprotected or feebly
      protected vaccinees. CONCLUSIONS: Our data demonstrate that postvaccinal titers
      are in linear dependence on the time elapsed since the vaccination and also
      evidence that some other immunological factors influence the outcome of
      vaccination.

PMID- 14587539
TI  - Psychophysiological stress in high school teachers.
AB  - OBJECTIVES: The aim of this study was to follow psychophysiological stress over a
      year with four repeated measurements in full-time employed high school teachers
      and to compare their results with those obtained in the part-time retired
      teachers, gardeners and rescue workers. MATERIALS AND METHODS: The subjects
      consisted of 17 (10 females, 7 males) full-time and 9 part-time employed teachers
      (7 females and 2 males) in three high schools, 12 female gardeners and 13 male
      rescue workers. The data on job conditions, well-being, and psychosomatic
      symptoms were obtained by a questionnaire. The perceived stress was recorded
      using a visual analogue scale. The neuroendocrine reactivity was assessed by
      determining the diurnal urine excretion of epinephrine and norepinephrine.
      Electromyography of the trapezius muscle was recorded during working days in all
      subjects and in full-time teachers on one day in the holiday season. Blood
      pressure and heart rate were measured in the morning and in the afternoon.
      RESULTS: Psychophysiological stress in the full-time employed teachers was at
      similar levels on all three working days in December, March and November.
      Recovery from psychophysiological stress of working period was observed on summer
      holidays. Blood pressure, static muscle tension, perceived strain, psychosomatic
      symptoms and epinephrine level decreased significantly during the summer holidays
      as compared to the working days. The full-time employed teachers reported more
      perceived stress and psychosomatic symptoms than the part-time retired teachers
      or gardeners and rescue workers. Also static muscle activity was higher in full
      time teachers than in rescue workers on the working days. CONCLUSIONS: More
      emphasis should be given to prevent psychophysiolocigal stress among teachers as
      well as to develop stress coping methods, and part-time working systems to
      facilitate work ability of aging teachers.

PMID- 14587540
TI  - The role of glutathione in metabolism of selected dimethylnaphthalenes in rat.
AB  - OBJECTIVES: Methylnaphthalenes have been used extensively as chemical
      intermediates in organic synthesis, as solvents for pesticides, sulphur and
      various aromatic compounds. A wide use of methylnaphthalenes has contributed to
      their emission into the environment. The aim of the study was to explain the role
      of glutathione in metabolism of selected dimethylnaphthalenes in rat. MATERIALS
      AND METHODS: The experiments were conducted on male rats of the strain outbred
      IMP:WIST The animals were administered a single intraperitoneal dose (600 mg/kg
      body weight) of dimethylnaphthalenes (1,2-DMN; 1,3-DMN; 1,4-DMN) or
      dimethylnaphthalenes-[ring-U-3H]: (1,2-DMN-[3H]; 1,3-DMN-[3H]; 1,4-DMN-[3H]). The
      analysis was performed after 4, 8, 24, 48 h. The biochemical parameters were
      indicated: hepatic and pulmonary GSH, a-GST, SDH, GPX in blood, and adduct levels
      in the liver and lung. RESULTS: The investigations demonstrated that a single
      intraperitoneal administration of dimethylnaphthalenes to rats at a dose of 600
      mg/kg body weight caused a substantial depletion of reduced glutathione (GSH)
      level both in the liver and lung. The activity of a-glutathione S-transferases in
      serum of experimental animals exposed to dimethylnaphthalenes increased only
      after 1,2-DMN administration, the compound for which in earlier investigations
      the largest number of sulphur-containing metabolites was found in urine. To
      evidence that deep GSH depletion in analyzed organs has no oxidative nature,
      glutathione peroxidase activity in blood was determined. CONCLUSIONS: Lack of
      changes in glutathione peroxidase and sorbitol dehydrogenase activity for all the
      investigated compounds suggests that significantly deep GSH depletion in liver
      was not of oxidative nature and did not lead to necrotic changes in produced
      metabolites binding with GSH.

PMID- 14587541
TI  - Histopathological screening for silicosis in autopsy cases of the Umtata area of
      the Eastern Cape Province.
AB  - The aim of this study was to determine the distribution of lung diseases in the
      autopsy subjects brought for medicolegal examination in the Transkei area. Two
      hundred histopathological slides were examined microscopically. Of them, 46
      subjects (23%) showed some kind of pathology. There were four kinds of lesions
      observed: dust reticulation (anthracosis), necrotizing granulomatous
      inflammation, tuberculosis and silicosis. Dust reticulation was observed in the
      lungs of 16 cases (8%), 14 of them (7%) were females and 2 males (1%), the
      deposition of carbon with some refractive silica particles seen in the lung
      fields predominated. These were the rural women aged 45-75 years. Narcotizing
      granulomatous inflammation of lungs that was probably tuberculosis and clear
      tuberculosis were found in 14 (7%) and 8 (4%) cases respectively.

PMID- 14587542
TI  - The NITE XML Toolkit: flexible annotation for multimodal language data.
AB  - Multimodal corpora that show humans interacting via language are now relatively
      easy to collect. Current tools allow one either to apply sets of time-stamped
      codes to the data and consider their timing and sequencing or to describe some
      specific linguistic structure that is present in the data, built over the top of
      some form of transcription. To further our understanding of human communication,
      the research community needs code sets with both timings and structure, designed
      flexibly to address the research questions at hand. The NITE XML Toolkit offers
      library support that software developers can call upon when writing tools for
      such code sets and, thus, enables richer analyses than have previously been
      possible. It includes data handling, a query language containing both structural
      and temporal constructs, components that can be used to build graphical
      interfaces, sample programs that demonstrate how to use the libraries, a tool for
      running queries, and an experimental engine that builds interfaces on the basis
      of declarative specifications.

PMID- 14587543
TI  - Remote Web usability testing.
AB  - Recently, various techniques for and approaches to extending usability testing
      beyond the traditional laboratories and technologies have emerged. Remote
      usability testing allows researchers to evaluate the usability of websites by
      gathering information from remote users. Several different approaches have been
      proposed, but they often require that the user perform particular installations
      or configurations. We introduce OpenWebSurvey, a software system for remote
      usability testing that can remotely record users' behavior while they surf the
      Internet and that requires no program installation or configuration.

PMID- 14587544
TI  - Tools for remote usability evaluation of Web applications through browser logs
      and task models.
AB  - The dissemination of Web applications is extensive and still growing. The great
      penetration of Web sites raises a number of challenges for usability evaluators.
      Video-based analysis can be rather expensive and may provide limited results. In
      this article, we discuss what information can be provided by automatic tools able
      to process the information contained in browser logs and task models. To this
      end, we present a tool that can be used to compare log files of user behavior
      with the task model representing the actual Web site design, in order to identify
      where users' interactions deviate from those envisioned by the system design.

PMID- 14587545
TI  - Beyond the five-user assumption: benefits of increased sample sizes in usability
      testing.
AB  - It is widely assumed that 5 participants suffice for usability testing. In this
      study, 60 users were tested and random sets of 5 or more were sampled from the
      whole, to demonstrate the risks of using only 5 participants and the benefits of
      using more. Some of the randomly selected sets of 5 participants found 99% of the
      problems; other sets found only 55%. With 10 users, the lowest percentage of
      problems revealed by any one set was increased to 80%, and with 20 users, to 95%.

PMID- 14587546
TI  - Off-line synchronization of measurements based on a common pseudorandom binary
      signal.
AB  - Postprocessing (or off line) synchronization methods rely on some overlap of
      information between two or more simultaneous measurements. The methods vary in
      the amount of explicit data needed to record the overlap: on the one hand, the
      full recording of an (absolute) time source for each measurement or, on the other
      hand, the reliance on information overlap of different parameters in the
      measurements. Whenever it is impossible to record the time from a central clock
      in all the simultaneous measurements, it is often possible to record asimple
      common signal. Using a binary pseudorandom noise (PRN) code to modulate the
      common signal enhances extraction of relative time information. The simplicity of
      this binary code makes it suitable for recording on various media (digitally or
      within audio and video streams) without the requirement for specialized and/or
      complex converters. The PRN technique has been applied successfully by NLR in
      several projects executed in a range of environments over the last decade and has
      been shown to provide time difference information with high precision.

PMID- 14587547
TI  - Reliability analysis of observational data: problems, solutions, and software
      implementation.
AB  - In the reliability analysis literature, little attention has been given to the
      various possible ways of creating a basis for the comparison required to compute
      observer agreement. One needs this comparison to turn a sequential list of
      behavioral records into a confusion matrix. It is shown that the way to do this
      depends on the research question one needs to answer. Four methods for creating a
      basis for comparison for the computation of observer agreement in observational
      data are presented. Guidelines are given for computing observer agreement in a
      way that fits one's goals. Finally, we discuss how these methods have been
      implemented in The Observer software. The Observer 4.1 supports all the methods
      that have been discussed. Most of these methods are not present in any other
      software package.

PMID- 14587548
TI  - Using the observer to analyze learning in virtual worlds.
AB  - In this study, we describe and analyze the ways in which high school students
      explored a virtual solar system (VSS). VSS is a nonimmersive virtual environment
      that affords visual manipulations of space by altering its frame of reference.
      The Observer software was used to code and analyze the participants' real-time
      free-exploration task. Two basic behaviors were identified across participants:
      establishing several home bases, and shifting between a still mode and a dynamic
      mode. Moreover, three overall exploration patterns emerged: the butterfly pattern
      represents a superficial mode of learning; the bee pattern represents an in-depth
      mode of studying the various celestial objects; and the eagle pattern represents
      a global approach of studying the complex system. This virtual reality
      environment promises to provide a setting in which to further study consistent
      patterns and individual differences in exploration strategies.

PMID- 14587549
TI  - Slot: a research platform for investigating multimodal communication.
AB  - In this article, we present the spatial logistics task (SLOT) platform for
      investigating multimodal communication between 2 human participants Presented are
      the SLOT communication task and the software and hardware that has been developed
      to run SLOT experiments and record the participants' multimodal behavior. SLOT
      offers a high level of flexibility in varying the context of the communication
      and is particularly useful in studies of the relationship between pen gestures
      and speech. We illustrate the use of the SLOT platform by discussing the results
      of some early experiments. The first is an experiment on negotiation with a one
      way mirror between the participants, and the second is an exploratory study of
      automatic recognition of spontaneous pen gestures. The results of these studies
      demonstrate the usefulness of the SLOT platform for conducting multimodal
      communication research in both human- human and human-computer interactions.

PMID- 14587550
TI  - Automatic recognition of eye blinking in spontaneously occurring behavior.
AB  - Previous research in automatic facial expression recognition has been limited to
      recognition of gross expression categories (e.g., joy or anger) in posed facial
      behavior under well-controlled conditions (e.g., frontal pose and minimal out-of
      plane head motion). We have developed a system that detects a discrete and
      important facial action (e.g., eye blinking) in spontaneously occurring facial
      behavior that has been measured with a nonfrontal pose, moderate out-of-plane
      head motion, and occlusion. The system recovers three-dimensional motion
      parameters, stabilizes facial regions, extracts motion and appearance
      information, and recognizes discrete facial actions in spontaneous facial
      behavior. We tested the system in video data from a two-person interview. The 10
      subjects were ethnically diverse, action units occurred during speech, and out-of
      plane motion and occlusion from head motion and glasses were common. The video
      data were originally collected to answer substantive questions in psychology and
      represent a substantial challenge to automated action unit recognition. In
      analysis of blinks, the system achieved 98% accuracy.

PMID- 14587551
TI  - Infrared imaging technology and biological applications.
AB  - Temperature is the most frequently measured physical quantity, second only to
      time. Infrared (IR) technology has been utilized successfully in astronomy (for a
      summary,see Hermans-Killam, 2002b) and in industrial and research settings
      (Gruner, 2002; Madding, 1982, 1989; Wolfe & Zissis, 1993) for decades. However,
      fairly recent innovations have reduced costs, increased reliability, and resulted
      in noncontact IR sensors offering mobile, smaller units of measurement (EOI,
      2002; Flir, 2000, 2001,2002). The advantages of using IR imaging are (1) rapidity
      in the millisecond range, facilitating measurement of moving targets, (2)
      noncontact procedures, allowing measurements of hazardous or physically
      inaccessible objects, (3) no interference and no energy lost from the target, (4)
      no risk of contamination, and (5) no mechanical effect on the surface of the
      object. All these factors have led to IR technology's becoming an area of
      interest for new kinds of applications and users. In both manufacturing and
      quality control, temperature plays an important role as an indicator of the
      condition of a product or a piece of machinery (EOI, 2002; Flir, 2000, 2001,
      2002; Raytek, 2002). In medical and veterinary applications, IR thermometry is
      increasingly used in organ diagnostics, in the evaluation of sports injuries and
      the progression of therapy, in disease evaluation (e.g, breast cancer, arthritis,
      and SARS; Flir, 2003), and in injury and inflammation examinations in horses,
      livestock (Tivey & Banhazi, 2002), and zoo animals (Hermans-Killam, 2002a;
      Thiesbrummel, 2002). Lastly, physiological expressions of life processes in
      animals (Kastberger, Winder, & Steindl, 2001; Stabentheiner, Kovac, & Hagmuller,
      1995; Stabentheiner, Kovac, & Schmaranzer, 2002; Stabentheiner & Schmarnzer,
      1987) and plants (Bermadinger-Stabentheiner & Stabentheiner, 1995) can be
      monitored. The most recent field in which IR technology has been applied is
      animal behavior. This article focuses on the practical options for noncontact IR
      thermometry--in particular, in biological applications.

PMID- 14587552
TI  - Toward standardized procedures for recording and describing 3-D shoulder
      movements.
AB  - Movements of the human upper extremity are difficult to measure, due to the
      specific structure of the limb. All arm movements are a combination of movements
      of the humerus relative to a moveable base: the scapula. Measurement of movements
      is, however, strongly hampered by the fact that the scapular movement is
      difficult to track when skin-based landmarks are used. A second complicating
      factor is the fact that a skin-based proximal landmark on the humerus is
      difficult to define, which directly affects attempts to describe accurately the
      movements of that segment. To solve these problems, special measurement
      procedures have been developed, which include the identification of landmarks for
      the scapula and the humerus and recording procedures for segment movements or the
      estimation of landmarks. Also, a definition of the three-dimensional description
      of motion is presented. These measurement procedures have now been applied in
      several experiments and have been proven to be successful.

PMID- 14587553
TI  - Image analysis of small animal feeding behavior.
AB  - The optimal design of behavioral experiments includes measures to minimize
      observer bias while maximizing researcher efficiency. To this end, we have
      developed a reliable, autonomous monitor of animal feeding behavior. Previous
      studies of caterpillar (Manduca sexta) feeding have relied on human observation
      for visual evaluation of food consumption at specific time points over the course
      of several hours. This method is eliminated by our new behavior rig, which
      collects data automatically. Individual animals are monitored via CCD cameras
      activated in sequence by a computer. Images are obtained at preset time intervals
      using a frame grabber to capture still pictures from the cameras. Subsequently,
      images are analyzed using software written in MatLab to determine food selection
      and quantify consumption.

PMID- 14587554
TI  - Correlating brain metabolism with stereotypic and locomotor behavior.
AB  - Many studies have shown that developmental cocaine exposure alters brain function
      and behavior, the present study examined the relationship between brain
      metabolism and behavioral responses to drug challenge. SKF 82958, a selective D1
      dopamine agonist, was administered to preweaning cocaine-exposed (50 mg/kg/day)
      rats and controls at 60 days of age. Deoxyglucose was administered 30 min later,
      during the peak behavioral response, to measure brain functional activity.
      Pearsonproduct-moment correlations of behavior (locomotor activity and
      stereotypic behavior) with rates of glucose metabolism in components of the
      nigrostriatal and mesolimbic circuits were analyzed. The analysis revealed that
      under saline-challenge conditions in control animals, rates of metabolism in
      mesolimbic regions are positively correlated to rates of locomotor activity,
      whereas in cocaine-treated rats, these correlations were absent. Following SKF
      challenge, a different pattern was seen; locomotor activity or stereotypic
      behavior was not correlated with mesolimbic or nigrostriatal metabolism,
      respectively, in controls but was positively correlated in cocaine-treated rats.
      Therefore, cocaine exposure during development enhances the coupling of
      metabolism in components of the mesolimbic and nigrostriatal dopamine systems
      with the behavioral output associated with these systems under drug-challenge
      conditions. This may be due to loss of inhibitory influences within the
      mesolimbic and nigrostriatal systems. Thus, the correlation of behavior and
      cerebral glucose metabolism provides a unique way of examining the effect of
      developmental cocaine exposure.

PMID- 14587555
TI  - Evaluation of living conditions of free-ranging animals by automated
      chronobiological analysis of behavior.
AB  - A biorhythmical method has been developed to assess behavior patterns and to
      evaluate the living conditions of animals that can be applied also to humans. All
      kinds of continuous and equidistant long-term recordings of behavior are suitable
      for this method. Time functions from an automatic telemetry system (ETHOSYS II)
      were analyzed macroscopically (comparison of daily levels) and microscopically
      (autocorrelation function and power spectral analysis). Degrees of functional
      coupling (DFCs) were calculated to identify and evaluate disturbances in
      behavior. Hierarchic frequency tuning of complex rhythmic functions of behaviors,
      leads primarily to period lengths that are synchronized with the 24-h period.
      DFCs, a measure of harmony between internal rhythms and the external 24-h period,
      were found to be high in well-adapted, healthy, and undisturbed individuals but
      were lowered during periods of adaptation, sickness, or social interaction.
      Specific stress conditions could be identified and evaluated in several species,
      under various conditions, using these biorhythmic analyses.

PMID- 14587556
TI  - Large-scale ensemble averaging of ambulatory impedance cardiograms.
AB  - Impedance cardiography has been used increasingly to measure human physiological
      responses to emotional and mentally engaging stimuli. The validity of large-scale
      ensemble averaging of ambulatory impedance cardiograms was evaluated for
      preejection period (PEP), interbeat interval, and dZ/dt(min) amplitude. We tested
      whether the average of "classical" 60-sec ensemble averages across periods with
      fixed activity, posture, physical load, social situation, and location could be
      accurately estimated from a single large-scale ensemble average spanning these
      entire periods. Impedance and electrocardiograms were recorded for about 24-h
      from 21 subjects. Recordings were scored by seven raters, using both methods for
      each subject. Good agreement (average intraclass correlation coefficient was .91)
      between both ensemble averaging methods was found for all three cardiac function
      measures. The results indicate that for unambiguous ambulatory impedance
      cardiograms, large-scale ensemble averaging is valid, which makes measuring
      prolonged changes in cardiac sympathetic activity by measuring ambulatory PEP
      feasible even in large epidemiological samples.

PMID- 14587557
TI  - State-dependent and odor-mediated anemotactic responses of a micro-arthropod on a
      novel type of locomotion compensator.
AB  - A novel type of locomotion compensator was designed and tested for its use in
      orientation behavior experiments with a predatory mite. In this apparatus,
      displacements of the test animal in the two-dimensional plane are recorded using
      video equipment and a servosphere that keeps the animal in focus. The x and y
      displacements are registered using two rotation encoders and are compensated
      using a pair of servo-motors, in such a way that the animal is always positioned
      on top of the sphere, yet moves freely. Well-fed and starved predators were
      tested for their responses to (1) still air, (2) a stimulus-free air flow, (3) an
      air flow with odors from uninfested Lima bean leaves, and (4) an air flow with
      odors from Lima bean leaves infested by plant-feeding mites, the prey of the
      predatory mites. Anemotactic responses of adult Phytoseiulus persimilis females
      were feeding state dependent. Well-fed predators moved downwind under Treatments
      1-3 but moved neither up- nor downwind in the presence of odors from infested
      plants (Treatment 4). Starved predators moved upwind under all treatments. These
      results are in agreement with those of earlier studies in a wind tunnel, and
      therefore, the new type of locomotion compensator (LC-100) offers an excellent
      method for studying the orientation behavior of micro-arthropods.

PMID- 14587558
TI  - Huge lobulated juvenile angiofibroma: sites of extension and selection of
      procedures for management.
AB  - OBJECTIVE: To review and report our experiences in the management of huge
      lobulated juvenile angiofibroma (JNA). MATERIALS AND METHODS: From 1980 to 2001,
      11 cases were diagnosed and treated in our department. Their clinical
      manifestations and the results of treatment were analyzed and evaluated, with
      particular attention to the anatomic sites of extension and the selection of
      choices for appropriate treatment. RESULTS: Owing to extranasopharyngeal
      extension, 6 to 12 different anatomic sites were occupied by each tumour,
      including the cheek (9 tumours) and middle cranial fossa (3 tumours). To remove
      these tumours, a transantral approach via midfacial degloving was usually used,
      with or without another incision and approach combined. When the middle cranial
      fossa is extensively involved by a tumour lobe, it should first be exposed and
      managed through a transtemporal-extradural or intradural approach. The internal
      carotid artery and cavernous sinus can be controlled distally. JNAs in 9 cases
      were resected completely without recurrence after following up for 1 to 22 years.
      The other 2 JNAs with large intracranial extension and serious intraoperative
      bleeding were removed subtotally. CONCLUSION: A huge JNA might occupy multiple
      anatomic sites, and the transantral approach via midfacial degloving is
      recommended as the best choice for its removal, with another incision and
      approach combined, if necessary.

PMID- 14587559
TI  - Audiologic presentation of cerebellopontine angle cholesteatoma.
AB  - OBJECTIVE: The aim of this study was to examine the audiologic presentation of
      patients with cerebellopontine angle (CPA) cholesteatoma. DESIGN: Retrospective
      case review. SETTING: Neuro-otologic tertiary referral centre. METHODS: The study
      population consisted of 11 patients with CPA cholesteatomas. The patients
      underwent a standard audiologic investigation in the preoperative setting, which
      consisted of pure-tone audiometry, speech audiometry, and auditory brainstem
      response (ABR). MAIN OUTCOME MEASURES: The audiologic parameters that were
      analyzed were the pure-tone threshold, pure-tone average (PTA), and speech
      discrimination scores (SDSs). The morphology and latency of the ABR were
      evaluated. In addition, the clinical and radiologic presentations of the lesions
      were reviewed. RESULTS: The mean PTA in the diseased ear was 22.6 dB HL (SD
      18.2), whereas in the contralateral ear, it was 19.1 dB HL (SD 19.6). In 4
      patients, the hearing loss was asymmetric, with the diseased ear being the worse
      ear. The mean SDS was 82.28% in the affected ear and 95.28% in the contralateral
      ear. ABR was abnormal in 9 of 10 cases (90%), with only the affected ear being
      abnormal in 4 cases. In the other 5 cases, the ABR was bilaterally abnormal.
      CONCLUSIONS: CPA cholesteatomas are very slow-growing lesions that involve the
      eighth cranial nerve. The paucity and insidious onset of symptoms mean that the
      diagnosis is often late, permitting the lesions to reach impressive dimensions at
      the time of diagnosis. Although magnetic resonance imaging represents the gold
      standard in the diagnosis of these lesions, ABR proved to be of value in the
      assessment of the auditory pathway, especially in those patients referred with a
      vague symptomatology and with normal hearing.

PMID- 14587560
TI  - Prevention of postlaryngectomy pharyngocutaneous fistula: the Memorial University
      experience.
AB  - OBJECTIVES: The purpose of this study was to compare the efficacy of a pectoralis
      major myogenous flap in the prevention of pharyngocutaneous fistula in patients
      who have undergone total laryngectomy. Our secondary objective was to estimate
      the economic saving to our health care system. DESIGN: Retrospective clinical
      study. SETTING: Grace General Hospital, St. Clare's Mercy Hospital, H. Bliss
      Murphy Cancer and Research Centre, St. John's, Newfoundland. MATERIALS AND
      METHODS: Two hundred and twenty-three consecutive total laryngectomy procedures
      performed between June 1978 and December 2001 were reviewed. The fistula rate in
      laryngectomy patients prior to 1988 without pectoralis major myogenous flaps
      (group A) was compared with that of patients after June 1988 who had this flap
      routinely used at primary surgery (group B). Analysis of risk factors within
      those two groups was essentially similar. RESULTS: In group A, the overall
      pharyngocutaneous fistula rate was 22.9%. The fistula rate in group B was less
      than 1%. CONCLUSION: Our study has demonstrated that at our tertiary care head
      and neck oncology centre, we have dramatically decreased the incidence of
      postlaryngectomy pharyngocutaneous fistula. By the routine addition of a
      pectoralis major myogenous flap to cover the pharyngeal defect at surgery, we
      have substantially and dramatically reduced patient morbidity and mortality and
      reduced hospital stay, with major financial savings to the health care system.

PMID- 14587561
TI  - Selective inhibition of cyclooxygenase 2 induces p27kip1 and skp2 in oral
      squamous cell carcinoma.
AB  - It has been shown that inhibition of cyclooxygenase 2 (COX-2) may cause growth
      arrest and reduced tumour formation in some human cancers; however, the mechanism
      is not fully known. In this study, we used an oral squamous cell carcinoma cell
      line to study growth inhibition and changes in critical cell cycle-regulating
      proteins induced by the selective COX-2 inhibitor celecoxib. Using cell viability
      assay, we established the optimal in vitro inhibitory dose of celecoxib and
      showed that inhibition of COX-2 markedly induces the expression of p27kip1, p21,
      waf1, and the F-box protein skp2. These results add new experimental data to our
      knowledge of the mechanism of cyclooxygenases on neoplastic cells.

PMID- 14587562
TI  - Tuberculosis in the upper aerodigestive tract and human immunodeficiency virus
      coinfections.
AB  - OBJECTIVE: To describe the clinical manifestations of tuberculosis in the upper
      aerodigestive tract. DESIGN: Retrospective chart analysis. SETTING: Srinagarind
      Hospital, Department of Otolaryngology, Faculty of Medicine, Khon Kaen
      University, Khon Kaen, Thailand. METHODS: A review of medical records of patients
      diagnosed with mycobacterial infection of the upper aerodigestive tract between
      January 1991 and December 2000. MAIN OUTCOME MEASURES: Presenting symptoms,
      clinical findings, pathologic findings, pulmonary involvement, and outcome of
      treatment. RESULTS: Forty-five patients presented with upper aerodigestive tract
      tuberculosis. The nasopharynx was involved in 23 patients, the larynx in 16, the
      tonsils in 6, and the soft palate in 1. One patient had tuberculous infections in
      both the nasopharynx and tonsils. The mean duration of symptoms before diagnosis
      was 2.1 months. The pathologic findings included caseous granuloma and/or
      positive acid-fast bacilli (AFB) in 39 cases and chronic granulomatous
      inflammation with negative AFB in 6 cases. Pulmonary tuberculosis was found in 19
      of the 36 patients who underwent radiography. A positive serologic test for human
      immunodeficiency virus (HIV) infection was found in 4 of 26 patients. These 26
      patients, who received a full course of treatment, responded well. CONCLUSION:
      The most common site of tuberculosis in the head and neck involved the cervical
      lymph nodes and nasopharynx. Upper aerodigestive tract tuberculosis is difficult
      to differentiate from carcinoma; thus, tissue biopsy is necessary for a definite
      diagnosis. Chest radiography and screening for HIV infection are recommended in
      all patients with upper aerodigestive tract tuberculosis.

PMID- 14587563
TI  - Migraine patients with or without vertigo: comparison of clinical and
      electronystagmographic findings.
AB  - OBJECTIVE: To find the differences between patients with migraine with and
      without vertigo. STUDY DESIGN: A prospective study. SETTING: Ambulatory dizziness
      centre of a tertiary referral hospital. METHODS: Eighty-four patients with
      migraine (31 with headache, 53 with headache and vertigo) according to the
      diagnostic criteria of migraine published by the International Headache Society
      in 1988 were included in the study. Patient history, vestibular tests,
      electronystagmography (ENG), and imaging studies were performed for differential
      diagnosis. MAIN OUTCOME MEASURES: Clinical findings and ENG parameters. RESULTS:
      Fifty-three of 84 patients (63%) had episodic vertigo attacks. Vertigo was
      independent from headache in 24 patients (45%). Vertigo symptoms always appeared
      later in the history of migraine headache. Headache started at age 27 +/- 8.3
      years and vertigo symptoms began 7.7 +/- 8.7 years later. The beginning age of
      the migraine and female-to-male ratio were significantly greater in the vertigo
      group. Fifty-eight of the 84 patients had ENG testing. Fifty-eight percent of the
      patients with migraine and 55% of the patients with migraine + vertigo had
      abnormal ENG findings. None of the tests except the Dix-Hallpike manoeuvre had a
      statistically significant difference between the two groups. CONCLUSION: The
      presence of the same ENG abnormalities in patients with pure headache shows that
      the vestibular pathways are also affected in these patients, even when there are
      no vestibular symptoms.

PMID- 14587564
TI  - Internet-based continuing medical education in otolaryngology: a survey of
      Canadian otolaryngologists.
AB  - OBJECTIVE: To assess the readiness of the Canadian otolaryngology community for
      an on-line continuing medical education (CME) program. METHODS: Data were
      obtained through surveys mailed to members of the Canadian Society of
      Otolaryngology-Head and Neck Surgery. RESULTS: Two hundred and eight of 321 (65%)
      surveys were returned. Seventy-six percent of the respondents indicated that they
      would be interested in participating in an on-line CME course. A greater
      proportion of younger otolaryngologists and those with community-based practices
      were interested in participating. A greater number of those with an academic
      practice were found to have convenient access to the Internet, the ability to
      post images on-line, and encountered cases they felt worthy of discussion and
      were willing to instruct/facilitate future on-line CME. Ninety-three percent of
      respondents described having easy access to the Internet, but only 32% said that
      they have the equipment necessary to post computed tomographic scans/audiograms
      on-line. Twenty-three percent had previous computer-based CME experience.
      Sinusitis and related topics were of greatest interest, with hearing loss/ear
      surgery and oncology following respectively. CONCLUSIONS: The data suggest that
      on-line CME would be welcomed and are feasible in the Canadian otolaryngology
      community.

PMID- 14587565
TI  - Early-deafened adult cochlear implant users: assessment of outcomes.
AB  - OBJECTIVE: To determine whether adults deafened in the prelingual and perilingual
      stages of speech development realize objective and subjective benefits from
      cochlear implantation. METHOD: Retrospective analysis of the open-set speech
      recognition and subjective data such as use and quality of life. RESULTS: Between
      1989 and 1999, 198 deafened adults underwent cochlear implantation at Sunnybrook
      and Women's College Health Sciences Centre. Of these, 44 patients were deafened
      pre- or perilingually. These subjects were implanted with a Nucleus 22, Nucleus
      24 (Cochlear Corporation, Denver, Colorado, USA), or Clarion (Advanced Bionics
      Corporation, Sylmar, California, USA) device. The average age at implantation was
      34 years (range 14-62 years). Significant differences in speech perception, as
      measured by a composite score of open-set word, phoneme, and sentence
      recognition, were found among groups who differed by type of education and
      communication training received in childhood. CONCLUSION: By and large, open-set
      speech recognition in prelingually and perilingually deafened adults is inferior
      to that achieved in postlingually deafened adults and varies according to the
      type of communication training they received. However, cochlear implants have
      significantly improved the overall communication skills and quality of life in
      all subgroups of patients.

PMID- 14587566
TI  - Comparison of voice characteristics following three different methods of
      treatment for laryngeal cancer.
AB  - INTRODUCTION: Laryngeal cancer treatment has become more complex and diversified
      in past decades. Many different methods of treatment have evolved, and most have
      been able to restore the patient's function and maintain some form of functional
      speech. This study was designed to evaluate the voice and speech characteristics
      of patients who have undergone different treatments for laryngeal cancer and to
      compare those characteristics with those of age- and sex-matched normal laryngeal
      speakers. METHODS: Twenty-two male subjects participated in the study. Five men
      were treated with radiation therapy, 6 men had supracricoid partial laryngectomy,
      6 men had undergone total laryngectomy with tracheoesophageal puncture, and 5 men
      were normal laryngeal speakers. Acoustic, aeromechanical, and perceptual
      assessments of speech were collected. RESULTS: Significant age effects were found
      for maximum phonation times. As age increased, maximum phonation time decreased
      (p < .005). Significant differences were found between groups for the following
      dependent variables: percentage of voiceless phonation, maximum phonation time,
      laryngeal airway resistance, subglottal pressure, oral flow, and word
      intelligibility. Trends in the data for differences between groups were noted for
      the following acoustic variables: noise-to-harmonics ratio, jitter, and shimmer.
      CONCLUSIONS: All patients developed or maintained a source of voicing after
      treatment and could use speech functionally, as demonstrated by normal sentence
      intelligibility. The radiation treatment group had voices that differed the least
      from the control group, whereas the opposite was true for the surgical groups,
      especially for those with total laryngectomy.

PMID- 14587567
TI  - Assessment of the accuracy and safety of the different methods used in mapping
      the frontal sinus.
AB  - INTRODUCTION: Frontal sinus obliteration continues to be the gold standard for
      frontal disease control and is often employed as a last resort of treatment after
      more conservative therapies fail. Different methods of sinus mapping have been
      previously reported and include (1) 6-foot Caldwell radiography, (2) sinus
      probing, and (3) sinus transillumination. Image-guided technology was recently
      introduced to clinical practice, but its utility in frontal sinus mapping has not
      been evaluated. OBJECTIVE: To assess the accuracy and safety of the previously
      reported methods of frontal sinus mapping and compare them with image-guided
      mapping. STUDY DESIGN: Five cadaveric heads were used. The four mapping methods
      were applied to each head along five different axes of the frontal bone: 0, 45,
      90, 135, and 180 degrees. The true frontal sinus margin was ascertained.
      Measurements were made from the true sinus limits to the margin points estimated
      by the four frontal sinus mapping methods. RESULTS: The image-guided mapping
      method provided was the most accurate when compared with the other mapping
      methods (p < .01). The image-guided mapping method was also the least likely to
      overshoot the real margin compared with the other mapping methods (p < .001). The
      template method was the least accurate and least safe method. CONCLUSIONS: Image
      guided mapping is the most accurate and safest method of mapping the frontal
      sinus margins.

PMID- 14587568
TI  - Sildenafil and nasal obstruction.
AB  - OBJECTIVE: Sildenafil (Viagra; Pfizer), a phosphodiesterase inhibitor, promotes
      penile erection through increased intracellular cyclic guanine monophosphate (a
      second messenger) in response to nitric oxide (a first messenger) release
      following sexual stimulation. Nitric oxide is involved in nasal vasodilation,
      secretion, and mucociliary clearance. The aim of this study was to assess the
      effect of sildenafil on nasal patency. DESIGN: Pilot study. SETTING: Teaching
      hospital. METHODS: Nasal patency was assessed by a visual analogue score and by
      measurement of the peak nasal inspiratory flow (PNIF) in five subjects before and
      after administration of sildenafil. MAIN OUTCOME MEASURES: Visual analogue score
      and PNIF. RESULTS: There was a significant increase in the subjective sensation
      of nasal obstruction (p = .003; -9.6 +/- 2.7, -15.4 to -3.7 [mean +/- SEM, 95%
      CI) and a significant reduction of PNIF (p < .001; 70.7 +/- 13.2, 43.1 to 98.3).
      CONCLUSIONS: This pilot study suggests that nasal patency may be reduced
      following the administration of sildenafil. The role of phosphodiesterase
      inhibitors in nasal physiology merits further investigation.

PMID- 14587570
TI  - Magical thinking and button battery ingestion.

PMID- 14587569
TI  - Bone that best matches the properties of the mandible.
AB  - OBJECTIVE: The main advantage of primary oromandibular reconstruction using free
      vascularized bone-containing flaps is improved oral function from (1) the
      maintenance of mandibular and soft tissue architecture and (2) dental
      rehabilitation through osseointegrated implants. Bone dimensions, volume,
      quality, and the ability of the bone to withstand masticatory forces are
      important factors in achieving successful osseointegration. Previous studies have
      objectively examined the dimensions of bones used in oromandibular
      reconstruction, but few have addressed their biomechanical properties. The
      purpose of this study was to compare the dimensional and biomechanical properties
      of the bones commonly used in oromandibular reconstruction with those of the
      mandible. METHODS: Eleven formalin-fixed cadavers were used. The mandibles,
      fibulae, iliac crests, scapulae, clavicles, second metatarsals, radii, and
      anterior ribs were harvested. Measurements of the dimensions of the bones were
      made with calipers at multiple sites. Three-point break strength and screw
      pulling force tests were then performed on all of the bones. RESULTS: The
      fibulae, iliac crests, and clavicles had dimensions that best matched those of
      the mandible. The three-point break strength and screw pulling force tests were
      consistently the highest for the mandibles and fibulae, followed by the
      clavicles, scapulae, iliac crests, metatarsals, radii, and ribs, in that order.
      CONCLUSIONS: The fibula is the bone that best matches the properties of the
      mandible.

PMID- 14587571
TI  - Tophaceous gout and pseudogout of the middle ear and the infratemporal fossa:
      case report and review of the literature.

PMID- 14587572
TI  - Bilateral complete supraorbital aeration.

PMID- 14587573
TI  - Automobile air-bag deployment and hearing loss.

PMID- 14587574
TI  - On the assessment of shooting sounds: loudness-level weightings versus A- and C
      weighted sound exposure levels (L).

PMID- 14587575
TI  - Random walk approach to wave propagation in wedges and cones.
AB  - Two- and three-dimensional Helmholtz equations in wedge-shaped and conical
      domains are addressed by the random walk method. The solutions of the Dirichlet
      problems in such domains are represented as mathematical expectations of
      specified functionals on trajectories of multidimensional random motions whose
      radial components run in a complex space while the angular components remain real
      valued. This technique is applied to the Sommerfeld problem of diffraction by a
      semi-infinite screen which is explicitly solved here in the probabilistic form.
      The numerical results confirm the efficiency of the random walk approach to the
      analysis of wave propagation.

PMID- 14587576
TI  - Experimental setup for measurement of acoustic power dissipation in lined ducts
      for higher order modes propagation with air mean-flow conditions.
AB  - A flow duct acoustic facility was developed to measure liner efficiency in
      attenuating higher order acoustic duct modes propagation conditions with mean air
      flow. The method is based on measurement, upstream and downstream of a liner, of
      the acoustic power produced by a periodic source. Directly measured total or
      modal acoustic powers are deduced from the local measurement, in both cross
      sections, of acoustic pressure, axial acoustic particle velocity, and axial mean
      flow velocity which are supplied by a probe made of a microphone and a single hot
      film. In this paper, the equipment, signal processing, and the data treatment
      process of this facility are first described. Then, information on the accuracy
      of the methodology is provided by a validation test performed with a rigid wall
      duct section. Finally, the results of an experiment carried out with a locally
      reacting liner and a mean flow velocity of 20 m/s will be presented. Measurements
      of the main attenuation frequency and of the main total acoustic power dissipated
      agree with the values for which the liner was designed. These results point out
      the limitations of the method presented to sources with high-level periodic
      sounds to provide a sufficient signal-to-noise ratio, the noise being produced by
      fluctuations of the turbulent flow.

PMID- 14587577
TI  - Nonlinear Fresnel diffraction of weak shock waves.
AB  - Fresnel diffraction at a straight edge is revisited for nonlinear acoustics.
      Considering the penumbra region as a diffraction boundary layer governed by the
      KZ equation and its associated jump relations for shocks, similarity laws are
      established for the diffraction of a step shock, an "N" wave, or a periodic
      sawtooth wave. Compared to the linear case described by the well-known Fresnel
      functions, it is shown that weak shock waves penetrate more deeply into the
      shadow zone than linear waves. The thickness of the penumbra increases as a power
      of the propagation distance, power 1 for a step shock, or 3/4 for an N wave, as
      opposed to power 1/2 for a periodic sawtooth wave or a linear wave. This is
      explained considering the frequency spectrum of the waveform and its nonlinear
      evolution along the propagation, and is confirmed by direct numerical simulations
      of the KZ equation. New formulas for the Rayleigh/Fresnel distance in the case of
      nonlinear diffraction of weak shock waves by a large, finite aperture are deduced
      from the present study.

PMID- 14587578
TI  - Numerical simulation of shock wave focusing at fold caustics, with application to
      sonic boom.
AB  - Weak shock wave focusing at fold caustics is described by the mixed type
      elliptic/hyperbolic nonlinear Tricomi equation. This paper presents a new and
      original numerical method for solving this equation, using a potential
      formulation and an "exact" numerical solver for handling nonlinearities.
      Validation tests demonstrate quantitatively the efficiency of the algorithm,
      which is able to handle complex waveforms as may come out from "optimized"
      aircraft designed to minimize sonic booms. It provides a real alternative to the
      approximate method of the hodograph transform. This motivated the application to
      evaluate the ground track focusing of sonic boom for an accelerating aircraft, by
      coupling CFD Euler simulations performed around the mock-up on an adaptated mesh
      grid, atmospheric propagation modeling, and the Tricomi algorithm. The chosen
      configuration is the European Eurosup mock-up. Convergence of the focused boom at
      the ground level as a function of the matching distance is investigated to
      demonstrate the efficiency of the numerical process. As a conclusion, it is
      indicated how the present work may pave the way towards a study on sonic
      superboom (focused boom) mitigation.

PMID- 14587579
TI  - Frequency response of nonlinear oscillations of air column in a tube with an
      array of Helmholtz resonators.
AB  - Nonlinear cubic theory is developed to obtain a frequency response of shock-free,
      forced oscillations of an air column in a closed tube with an array of Helmholtz
      resonators connected axially. The column is assumed to be driven by a plane
      piston sinusoidally at a frequency close or equal to the lowest resonance
      frequency with its maximum displacement fixed. By applying the method of multiple
      scales, the equation for temporal modulation of a complex pressure amplitude of
      the lowest mode is derived in a case that a typical acoustic Mach number is
      comparable with the one-third power of the piston Mach number, while the relative
      detuning of a frequency is comparable with the quadratic order of the acoustic
      Mach number. The steady-state solution gives the asymmetric frequency response
      curve with bending (skew) due to nonlinear frequency upshift in addition to the
      linear downshift. Validity of the theory is checked against the frequency
      response obtained experimentally. For high amplitude of oscillations, an effect
      of jet loss at the throat of the resonator is taken into account, which
      introduces the quadratic loss to suppress the peak amplitude. It is revealed that
      as far as the present check is concerned, the weakly nonlinear theory can give
      quantitatively adequate description up to the pressure amplitude of about 3% to
      the equilibrium pressure.

PMID- 14587580
TI  - Two-dimensional streaming flows induced by resonating, thin beams.
AB  - Miniaturized resonating slender beams are finding increased applications as
      fluidic actuators for portable electronics cooling. Piezoelectric and ultrasonic
      "fans" drive a flexural mode of the beam into resonance thus inducing a streaming
      flow, which can be used to cool microelectronic components. This paper presents
      analytical, computational, and experimental investigations of the incompressible
      two-dimensional streaming flows induced by resonating thin beams. Closed-form
      analytical streaming solutions are presented first for an infinite beam. These
      are used to motivate a computational scheme to predict the streaming flows from a
      baffled piezoelectric fan. Experiments are conducted to visualize the asymmetric
      streaming flows from a baffled piezoelectric fan and the experimental results are
      found to be in close agreement with the predicted results. The findings are
      expected to be of relevance in the optimal design and positioning of these solid
      state devices in cooling applications.

PMID- 14587581
TI  - Calculating the micrometeorological influences on the speed of sound through the
      atmosphere in forests.
AB  - A key element in determining point-to-point acoustic transmission within and
      above forests is modeling the variation (with height above ground) of the
      effective speed of sound. Effective speed of sound is readily derived from
      estimates of air temperature, relative humidity, and wind velocity. However,
      meteorological models for the forest canopy vary from comparatively simple to
      academically complex, requiring different amounts and numbers of inputs and
      computer capabilities. In addition, not all canopy profile models are suitable
      for acoustic applications. In this paper, a meteorological computer model for the
      forest canopy is developed to derive continuous profiles of effective sound speed
      from the ground to 3 h, where h is the height of the canopy. In turn, these
      profiles are used to make some initial approximations of short-range acoustic
      transmission loss through a uniform forest stand for typical clear sky, midday
      atmospheric conditions. Also, a radiative transfer and energy budget algorithm is
      incorporated into the model to obtain the appropriate heat source profile for any
      time of day. Thus, physics-based micrometeorology is coupled to acoustics for
      future applications of acoustic information in forest environments.

PMID- 14587582
TI  - Evaluation of rosette infrasonic noise-reducing spatial filters.
AB  - This paper presents results from recent tests of rosette infrasonic noise
      reducing spatial filters at the Pinon Flat Observatory in southern California.
      Data from 18- and 70-m aperture rosette filters and a reference port are used to
      gauge the reduction in atmospheric wind-generated noise levels provided by the
      filters and to examine the effect of these spatial filters on spatially coherent
      acoustic signals in the 0.02- to 10-Hz band. At wind speeds up to 5.5 m/s, the 18
      m rosette filter reduces wind noise levels above 0.2 Hz by 15 to 20 dB. Under the
      same conditions, the 70-m rosette filter provides noise reduction of up to 15 to
      20 dB between 0.02 and 0.7 Hz. Standing wave resonance inside the 70-m filter
      degrades the reception of acoustic signals above 0.7 Hz. The fundamental mode of
      the resonance, 15 dB above background, is centered at 2.65-Hz and the first odd
      harmonic is observed at 7.95 Hz in data from the large filter. Analytical
      simulations accurately reproduce the noise reduction and resonance observed in
      the 70-m filter at all wind speeds above 1.25 m/s. Resonance theory indicates
      that internal reflections that give rise to the resonance observed in the
      passband are occurring at the summing manifolds, and not at the inlets. Rosette
      filters are designed for acoustic arrivals with infinite phase velocity. The
      plane-wave response of the 70-m rosette filter has a strong dependence on
      frequency above 3.5 Hz at grazing angles of less than 15 degrees from the
      horizontal. At grazing angles, complete cancellation of the signal occurs at 5
      Hz. Theoretical predictions of the phase and amplitude response of 18- and 70-m
      rosette filters, that take into account internal resonance and time delays
      between the inlets, compare favorably with observations derived from a cross
      spectral analysis of signals from the explosion of a large bolide.

PMID- 14587583
TI  - A modified Khokhlov-Zabolotskaya equation governing shear waves in a prestrained
      hyperelastic solid.
AB  - Weakly nonlinear, weakly diffracting, two-dimensional shear waves propagating in
      a prestrained hyperelastic solid are examined. A modification of the classical
      Khokhlov-Zabolotskaya equation is derived using a systematic perturbation scheme.
      Both dissipative and nondissipative materials were considered. The principal
      effect of the prestrain was seen to be the inclusion of a quadratic nonlinearity
      to the cubic nonlinearity found in the case of zero prestrain. Further new
      results include the shock jump relations and the prediction of shocks having a
      speed which is identical to the nonlinear wave speed ahead of or behind the
      shock. Explicit expressions for the nonlinearity coefficients for the special
      case of a Blatz-Ko material were provided.

PMID- 14587584
TI  - Numerical simulation of the excitation of a Helmholtz resonator by a grazing
      flow.
AB  - The process of noise generation in a flow-excited Helmholtz resonator involves
      strong interaction between a time-dependent fluid flow and acoustic resonance.
      Quantitative prediction of this effect, requiring accurate prediction of time
      dependent features of a flow over complex three-dimensional bodies, turbulence
      modeling, compressibility and Mach number effects, is one of the major challenges
      to computational fluid dynamics. In this paper a numerical procedure based on the
      lattice kinetic equation, combined with the RNG turbulence model, is applied to
      describe a well-controlled experiment on acoustic resonance excitation by a
      grazing flow [Nelson et al., J. Sound Vib. 78, 15-27 (1981)]. The achieved
      agreement between numerical and physical experiments is very good. The
      simulations reveal a universality transformation enabling comparison of the data
      for different inlet conditions.

PMID- 14587585
TI  - Sound absorption by suspensions of nonspherical particles: measurements compared
      with predictions using various particle sizing techniques.
AB  - Knowledge of the particle size distribution is required in order to predict
      ultrasonic absorption in polydisperse particulate suspensions. This paper shows
      that the method used to measure the particle size distribution can lead to
      important differences in the predicted absorption. A reverberation technique
      developed for measuring ultrasonic absorption by suspended particles is used to
      measure the absorption in suspensions of nonspherical particles. Two types of
      particulates are studied: (i) kaolin (china clay) particles which are platelike
      in form; and (ii) calcium carbonate particles which are more granular. Results
      are compared to theoretical predictions of visco-inertial absorption by
      suspensions of spherical particles. The particle size distributions, which are
      required for these predictions, are measured by laser diffraction, gravitational
      sedimentation and centrifugal sedimentation, all of which assume spherical
      particles. For a given sample, each sizing technique yields a different size
      distribution, leading to differences in the predicted absorption. The particle
      size distributions obtained by gravitational and centrifugal sedimentation are
      reinterpreted to yield a representative size distribution of oblate spheroids,
      and predictions for absorption by these spheroids are compared with the
      measurements. Good agreement between theory and measurement for the flat kaolin
      particles is obtained, demonstrating that these particles can be adequately
      represented by oblate spheroids.

PMID- 14587586
TI  - Consistency and accuracy of perturbative inversion methods for group travel time
      data.
AB  - Perturbation theory for ocean acoustic modal group speed responses to small
      environmental changes is investigated with regard to its applicability to ocean
      acoustic tomography. Assuming adiabaticity, the inverse problem for each vertical
      eigenmode is an integral equation whose kernel involves the eigenfunction and its
      frequency derivative. A proof is given for the equivalence of two dissimilar
      forms of the integral equation. Numerical examples are given for the inversion
      kernel for four types of sound-speed profiles, and then the parameter range
      (amplitude and scale size) in which perturbation theory is accurate is examined.
      It is found that the range of validity is determined not only by the amplitude of
      the perturbations, but also by their vertical scale size.

PMID- 14587587
TI  - Seabed reflection measurement uncertainty.
AB  - The seabed reflection coefficient is a fundamental property of the ocean
      waveguide. Measurements of the frequency and angular dependence of the reflection
      coefficient can provide information about the geoacoustic properties of the
      seabed or can be used as an input to propagation models. The uncertainty of the
      measurements must be known in order to determine prediction uncertainties for the
      acoustic field and/or the geoacoustic properties. Analysis indicates that the
      reflection measurements have a standard deviation from +/- 0.5-1 dB at full
      angular resolution depending on frequency and experiment geometry. The dominant
      contribution to the error is source amplitude variability, and a new processing
      approach was developed that reduces the error for frequencies above a few hundred
      Hz. Further reduction in the uncertainty can be obtained by averaging in angle,
      for example, a +/- 1 degrees angle averaging leads to a standard deviation of
      less than +/- 0.5 dB. Errors in the angle estimate are a few tenths of a degree
      from 0-34 degrees grazing angle: the crucial angular range for predicting long
      range propagation or for geoacoustic property inversion.

PMID- 14587588
TI  - Inversion for sediment geoacoustic properties at the New England Bight.
AB  - This article discusses inversions for bottom geoacoustic properties using
      broadband acoustic signals obtained from explosive sources. Two different
      inversion schemes for estimating the compressional wave speeds and attenuation
      are presented in this paper. In addition to these sediment parameters, source
      receiver range is also estimated using the arrival time data. The experimental
      data used for the inversions are SUS charge explosions acquired on a vertical
      hydrophone array during the Shelf Break Primer Experiment conducted south of New
      England in the Middle Atlantic Bight in August 1996. The modal arrival times are
      extracted using a wavelet analysis. In the first inversion scheme, arrival times
      corresponding to various modes and frequencies from 10 to 200 Hz are used for the
      inversion of compressional wave speeds. A hybrid inversion scheme based on a
      genetic algorithm (GA) is used for the inversion. In an earlier study, Potty et
      al. [J. Acoust. Soc. Am. 108(3), 973-986 (2000)] have used this hybrid scheme in
      a range-independent environment. In the present study results of range-dependent
      inversions are presented. The sound speeds in the water column and bathymetry are
      assumed range dependent, whereas the sediment compressional wave speeds are
      assumed range independent. The variations in the sound speeds in the water column
      are represented using empirical orthogonal functions (EOFs). The replica fields
      corresponding to the unknown parameters were constructed using adiabatic theory.
      In the second inversion scheme, modal attenuation coefficients are calculated
      using modal amplitude ratios. The ratios of the modal amplitudes are also
      calculated using time-frequency diagrams. A GA-based inversion scheme is used for
      this search. Finally, as a cross check, the computed compressional wave speeds
      along with the modal arrival times were used to estimate the source-receiver
      range. The inverted sediment properties and ranges are seen to compare well with
      in situ measurements and historical data.

PMID- 14587589
TI  - Echo strength and density structure of Hawaiian mesopelagic boundary community
      patches.
AB  - A broadband sonar system and digital camera with strobe lights were mounted on a
      vertically profiling frame with a depth sensor. The echo strengths and densities
      of animals within individual mesopelagic boundary community patches were
      investigated as a function of depth. Time and distance from shore were also
      investigated. Simultaneous surface echosounder surveys permitted comparison of
      density estimates from two techniques. Echo strength values suggest nearshore
      boundary community animals are primarily myctophid fishes, which was confirmed by
      preliminary photographic evidence. Echo strength varied significantly as a
      function of distance from the shoreline and time. These measures of echo strength
      are important for estimating density from a surface echosounder. Density
      estimates from these revised echo strengths compare well with those made with
      echo highlight counting, which is independent of echo strength. These density
      measures suggest that previous density estimates were too low but do not change
      the conclusions of these studies. Vertical microstructure in density was apparent
      but animal size and compositional structure was not evident within a patch. Patch
      edges were abrupt, with no differences in the density or echo strength from patch
      interiors. These edges were generally straight, with a sharp drop in density to
      the background density of zero. Estimates of animal size as a function of time
      provide information about the diel migration patterns of these mesopelagic
      animals.

PMID- 14587590
TI  - Bubble oscillations driven by aspherical ultrasound in liquid.
AB  - In this paper we study the bubble dynamics driven by an aspherical acoustic
      field, based on the theory of hydrodynamics. Evolution equations for an
      aspherical bubble are derived under the aspherical acoustic driving. The
      numerical calculations show that the aspherical bubble can oscillate stably and
      periodically under suitable conditions, which is out of the explanation of
      spherical perturbation theory. Furthermore, under some controlling parameters,
      the aspherical distortion can either grow rapidly, leading to the bubble's
      breakdown, or decay gradually making the bubble spherical, which is similar to
      the result of the perturbation theory driven by a spherical ultrasound.

PMID- 14587591
TI  - A cascade thermoacoustic engine.
AB  - A cascade thermoacoustic engine is described, consisting of one standing-wave
      stage plus two traveling-wave stages in series. Most of the acoustic power is
      produced in the efficient traveling-wave stages. The straight-line series
      configuration is easy to build and allows no Gedeon streaming. The engine
      delivers up to 2 kW of acoustic power, with an efficiency (the ratio of acoustic
      power to heater power) of up to 20%. An understanding of the pressure and volume
      velocity waves is very good. The agreement between measured and calculated powers
      and temperatures is reasonable. Some of the measured thermal power that cannot be
      accounted for by calculation can be attributed to Rayleigh streaming in the two
      thermal buffer tubes with the largest aspect ratios. A straightforward extension
      of this work should yield cascade thermoacoustic engines with efficiencies of
      around 35-40% of the Carnot efficiency.

PMID- 14587592
TI  - Beampattern control of a microphone array to minimize secondary source
      contamination.
AB  - A null-steering technique is adapted and applied to a linear delay-and-sum
      beamformer in order to measure the noise generated by one of the propellers of a
      1/8 scale twin propeller aircraft model. The technique involves shading the
      linear array using a set of weights, which are calculated according to the
      locations onto which the nulls need to be steered (in this case onto the second
      propeller). The technique is based on an established microwave antenna theory,
      and uses a plane-wave, or far field formulation in order to represent the
      response of the array by an nth-order polynomial, where n is the number of array
      elements. The roots of this polynomial correspond to the minima of the array
      response, and so by an appropriate choice of roots, a polynomial can be
      generated, the coefficients of which are the weights needed to achieve the
      prespecified set of null positions. It is shown that, for the technique to work
      with actual data, the cross-spectral matrix must be conditioned before array
      shading is implemented. This ensures that the shading function is not distorted
      by the intrinsic element weighting which can occur as a result of the directional
      nature of aeroacoustic systems. A difference of 6 dB between measurements before
      and after null steering shows the technique to have been effective in eliminating
      the contribution from one of the propellers, thus providing a quantitative
      measure of the acoustic energy from the other.

PMID- 14587593
TI  - High-sensitivity photoacoustic leak testing.
AB  - The photoacoustic effect may be exploited for the detection and localization of
      gas leaks from otherwise sealed components. The technique involves filling the
      test component with a tracer gas, and radiating the component to produce
      photoacoustic sound from any leak site where tracer gas is present. This paper
      describes demonstration experiments utilizing 10.6-micro radiation from a carbon
      dioxide laser and sulfur hexafluoride as a tracer gas for photoacoustic leak
      testing at leak rates between 6 x 10(-5) cm3/s (1 cm3 in 4.6 h) and 5 x 10(-9)
      cm3/s (1 cm3 in 6.3 years). The technique may reach or exceed the capabilities of
      the most sensitive commercial leak test systems using helium mass-spectrometers.
      In addition, comparison of the measured results to a simple scaling law suggests
      that tracer gas cloud geometry influences the photoacoustic signal amplitude.

PMID- 14587594
TI  - Passively minimizing structural sound radiation using shunted piezoelectric
      materials.
AB  - Two methods are presented to determine optimal inductance and resistance values
      of the shunt circuit across a piezoceramic material, which is bonded to a simply
      supported plate in order to minimize sound radiation from the plate. The first
      method (DH) makes use of den Hartog's damped vibration absorber principle. The
      second method (SM) uses the Sherman Morrison matrix inversion theorem. The
      effectiveness of each method is compared with regard to minimizing total acoustic
      sound-power radiation and acoustic pressure at a point. Optimization algorithms
      and case studies are presented using a linearized model for the piezoceramic and
      using a nonlinear model for the piezoceramic that accounts for the inherent
      dielectric hysteresis. Case studies demonstrate that the second method (SM)
      results in superior performance, under both linear and nonlinear system
      assumptions. Studies also illustrate that, if the nonlinearity in the system is
      significant, it must be incorporated in the optimization process.

PMID- 14587595
TI  - Scale-model study of the effectiveness of highway noise barriers.
AB  - A scale-model facility was developed to test the insertion loss (IL) of highway
      noise barriers. Three model materials were utilized to simulate packed-earth
      berms and ground (expanded polystyrene), vertical walls (dense polystyrene), and
      roadways (varnished particleboard). Thirty-eight noise-barrier configurations
      were tested and used to compare how IL varied with changes to the barrier profile
      for walls, berms, and combinations of walls and berms for receivers at a
      representative, highway-adjacent location. The atmospheric conditions were
      assumed to be homogeneous and nonrefracting. Changes of barrier surface impedance
      were also assessed. A highway line source was simulated by positioning both an
      air-jet point source and a receiver microphone at a series of equally spaced
      points, in order to form an array of source-receiver measurement pairs making
      differing angles of propagation to the noise-barrier crest line. The IL
      measurement results are presented in unweighted third-octave bands. In addition,
      total A-weighted insertion losses (ILA) were obtained by applying an A-weighted,
      traffic-noise spectrum. When a berm was modeled with surface impedance closely
      matching that of packed earth, it was found that walls outperformed berms by 1 to
      2 dBA. When the surface impedance of a berm was modeled to be acoustically soft,
      the ILA increased sufficiently to favor berms by about 2 dBA. The result for an
      acoustically soft berm does not support the long-standing practice of assuming
      that earth berms outperform walls by 3 dBA, but is consistent with the
      performance predicted by newer prediction algorithms. When the slopes of berms
      were made shallower, the IL generally decreased for a berm alone, but generally
      increased in cases with a wall atop the berm.

PMID- 14587596
TI  - Hearing protection: surpassing the limits to attenuation imposed by the bone
      conduction pathways.
AB  - With louder and louder weapon systems being developed and military personnel
      being exposed to steady noise levels approaching and sometimes exceeding 150 dB,
      a growing interest in greater amounts of hearing protection is evident. When the
      need for communications is included in the equation, the situation is even more
      extreme. New initiatives are underway to design improved hearing protection,
      including active noise reduction (ANR) earplugs and perhaps even active
      cancellation of head-borne vibration. With that in mind it may be useful to
      explore the limits to attenuation, and whether they can be approached with
      existing technology. Data on the noise reduction achievable with high-attenuation
      foam earplugs, as a function of insertion depth, will be reported. Previous
      studies will be reviewed that provide indications of the bone-conduction (BC)
      limits to attenuation that, in terms of mean values, range from 40 to 60 dB
      across the frequencies from 125 Hz to 8 kHz. Additionally, new research on the
      effects of a flight helmet on the BC limits, as well as the potential attenuation
      from deeply inserted passive foam earplugs, worn with passive earmuffs, or with
      active-noise reduction (ANR) earmuffs, will be examined. The data demonstrate
      that gains in attenuation exceeding 10 dB above the head-not-covered limits can
      be achieved if the head is effectively shielded from acoustical stimulation.

PMID- 14587597
TI  - An angle-by-angle approach to predicting broadband high-frequency sound fields in
      rectangular enclosures with experimental comparison.
AB  - Experiments were performed on an elongated rectangular acoustic enclosure with
      different levels of absorptive material placed on side walls and an end wall. The
      acoustic source was a broadband high-frequency sound from a loudspeaker flush
      mounted to an end wall of the enclosure. Measurements of sound-pressure levels
      were averaged in cross sections of the enclosure and then compared to theoretical
      results. Discrepancies between the experimental results and theoretical
      predictions that treated all incidence angles as equally probable led to the
      development of an angle-by-angle approach. The new approach agrees well with the
      experimentally obtained values. In addition, treating the absorptive material as
      bulk reacting rather than point reacting was found to significantly change the
      theoretical value for the absorption coefficient and to improve agreement with
      experiment. The new theory refines an earlier theory based on power conservation
      and locally diffuse assumptions. Furthermore, the new theory includes both the
      angle of incidence effects on the resistive and reactive properties of the
      absorptive material, and the effects of angle filtering, i.e., that reflecting
      waves associated with shallow angles become relatively stronger than those
      associated with steep angles as a function of distance from the source.

PMID- 14587598
TI  - Behavioral criterion quantifying the edge-constrained effects on foams in the
      standing wave tube.
AB  - The influence of mounting conditions on the measurement of the sound absorption
      coefficient is investigated. More specifically, the effects of a circumferential
      edge constraint applied on elastic foams in a standing wave tube are studied. The
      objective is to identify the foams for which it is possible to measure the
      theoretical absorption coefficient using the tube. This identification relies on
      the evaluation of a new parameter, the Frame Acoustical Excitability (FAE), based
      on the foams' physical properties. In order to quantify the difference between
      the measured and theoretical absorptions, a linear correlation coefficient is
      evaluated for a wide range of foams with various sample sizes. The calculated
      correlation coefficients are then sorted in terms of the FAE. It is shown that as
      the value of FAE increases, the difference between the measured and theoretical
      absorption coefficients becomes more significant. A critical value of FAE, below
      which the theoretical absorption can be efficiently measured using the tube, is
      established. Through the use of this elasto-acoustic criterion, an experimenter
      can make an educated guess as to which absorption is measured with the tube: the
      theoretical absorption or one that is affected by either the edge constraint or
      the sample's dimensions.

PMID- 14587599
TI  - Blind deconvolution applied to acoustical systems identification with supporting
      experimental results.
AB  - Many acoustical applications require the analysis of a signal that is corrupted
      by an unknown filtering function. Examples arise in the areas of noise or
      vibration control, room acoustics, structural vibration analysis, and speech
      processing. Here, the observed signal can be modeled as the convolution of the
      desired signal with an unknown system impulse response. Blind deconvolution
      refers to the process of learning the inverse of this unknown impulse response
      and applying it to the observed signal to remove the filtering effects. Unlike
      classical deconvolution, which requires prior knowledge of the impulse response,
      blind deconvolution requires only reasonable prior estimates of the input
      signal's statistics. The significant contribution of this work lies in
      experimental verification of a blind deconvolution algorithm in the context of
      acoustical system identification. Previous experimental work concerning blind
      deconvolution in acoustics has been minimal, as previous literature concerning
      blind deconvolution uses computer simulated data. This paper examines experiments
      involving three classical acoustic systems: driven pipe, driven pipe with open
      side branch, and driven pipe with Helmholtz resonator side branch. Experimental
      results confirm that the deconvolution algorithm learns these systems' inverse
      impulse responses, and that application of these learned inverses removes the
      effects of the filters.

PMID- 14587600
TI  - Sensor array beamforming using random channel sampling: the aggregate beamformer.
AB  - The aggregate (AGG) beamformer can provide significant savings in hardware and
      software cost and complexity relative to conventional beamformers while retaining
      equivalent directional performance. The key to achieving the savings is
      collecting data from array channels in a random sequence, rather than
      simultaneously or sequentially. This allows the AGG beamformer to convert
      unwanted off-beam signals into wideband noise that can then be reduced by
      filtering. The total sampling rate is chosen to obtain the desired residual noise
      level and signal bandwidth. It is independent of the number of sensors. Analog
      anti-alias filters normally are not required, since the Nyquist frequency is
      determined by the total sampling rate, not the (lower) per-channel sampling rate.
      Beamformer delay quantization and steering resolution are greatly improved
      relative to conventional beamforming without the need for data interpolation. The
      beamformed signal, prior to decimation filtering, is obtained without arithmetic
      operations on the data. Low front-end hardware-complexity makes the AGG
      beamformer suitable for highly integrated systems. The number of sensors in the
      array can be altered without re-configuring buffers or altering the sampling
      rate. The principles of the AGG beamformer are introduced, and simulation and
      experimental results demonstrate performance.

PMID- 14587601
TI  - A phenomenological model for the responses of auditory-nerve fibers. II.
      Nonlinear tuning with a frequency glide.
AB  - A computational model was developed to simulate the responses of auditory-nerve
      (AN) fibers in cat. The model's signal path consisted of a time-varying bandpass
      filter; the bandwidth and gain of the signal path were controlled by a nonlinear
      feed-forward control path. This model produced realistic response features to
      several stimuli, including pure tones, two-tone combinations, wideband noise, and
      clicks. Instantaneous frequency glides in the reverse-correlation (revcor)
      function of the model's response to broadband noise were achieved by carefully
      restricting the locations of the poles and zeros of the bandpass filter. The pole
      locations were continuously varied as a function of time by the control signal to
      change the gain and bandwidth of the signal path, but the instantaneous frequency
      profile in the revcor function was independent of sound pressure level,
      consistent with physiological data. In addition, this model has other important
      properties, such as nonlinear compression, two-tone suppression, and reasonable
      Q10 values for tuning curves. The incorporation of both the level-independent
      frequency glide and the level-dependent compressive nonlinearity into a
      phenomenological model for the AN was the primary focus of this work. The ability
      of this model to process arbitrary sound inputs makes it a useful tool for
      studying peripheral auditory processing.

PMID- 14587602
TI  - Time-frequency analyses of transient-evoked stimulus-frequency and distortion
      product otoacoustic emissions: testing cochlear model predictions.
AB  - Time-frequency representations (TFRs) of otoacoustic emissions (OAEs) provide
      information simultaneously in time and frequency that may be obscured in waveform
      or spectral analyses. TFRs were applied to transient-evoked stimulus-frequency
      (SF) and distortion-product (DP) OAEs to test cochlear model predictions. SFOAEs
      and DPOAEs were elicited in 18 normal-hearing subjects using gated tones and tone
      pips. Synchronous spontaneous (SS) OAEs were measured to assess their
      contributions to SFOAEs and DPOAEs. A common form of TFR of measured OAEs was a
      collection of frequency-specific components often aligned with SSOAE sites, with
      each component characterized by one or more brief segments or a single long
      duration segment. The spectral envelope of evoked OAEs differed from that of the
      evoking stimulus. Strong emission regions or cochlear "hot spots" were detected,
      and sometimes accounted for OAE energy observed outside the stimulus bandwidth.
      Contributions of hot spots and multiple internal reflections to the OAE, and
      differences between measured and predicted OAE spectra, increased as stimulus
      level decreased, consistent with level-dependent changes in the estimated
      cochlear reflectance. Suppression and frequency-pulling effects between
      components were observed. A recursive formulation was described for the linear
      coherent reflection emission theory [Zweig and Shera, J. Acoust. Soc. Am. 98,
      2018-2047 (1995)] that is well suited for time-domain calculations.

PMID- 14587603
TI  - Physiological vulnerability of distortion product otoacoustic emissions from the
      amphibian ear.
AB  - The physiological vulnerability of distortion product otoacoustic emissions
      (DPOAEs) was investigated in the leopard frog, Rana pipiens pipiens. For each
      frog, DPOAEs were recorded from the amphibian and the basilar papillae.
      Measurements were taken before and after either the arrest of oxygen supply due
      to cardioectomy, or the destruction of the central nervous system (CNS). DPOAEs
      in response to high-level stimuli (> 75 dB SPL) were rather robust to these
      insults during the first two hours post surgery. In contrast, DPOAE amplitudes in
      response to low-level stimuli (< 75 dB SPL) decreased significantly. On average,
      low-level emissions from the amphibian papilla disappeared within 6 min for
      cardioectomy, and after 13 min for CNS destruction. In the basilar papilla, low
      level DPOAEs disappeared more slowly: on average after 34 min following
      cardioectomy, and after 58 min for CNS destruction. The difference in
      physiological vulnerability between low- and high-level emissions is similar to
      that in mammals and a lizard. The difference between the DPOAE decay rate of the
      frog's amphibian and basilar papillae suggests important differences between the
      hearing mechanisms of the papillae.

PMID- 14587604
TI  - Electrical field interactions in different cochlear implant systems.
AB  - The goal of this study was to evaluate electrical field interactions produced by
      the stimulation of different types of intracochlear electrodes in 12 adult
      subjects (three Ineraid, four Clarion S-Series, three S-Series with the electrode
      positioning system-EPS and two Clarion HiFocus-I with the EPS). Psychophysical
      measurements were conducted with biphasic stimuli (813 pulse per second, 153.8
      micros/phase). "Perturbation" signals (300 ms) were applied to one electrode
      chosen at the middle of the array and their effects on detection thresholds of
      "probe" signals (30 ms) were measured on the neighbor basal electrode.
      Perturbation levels were set below the detection threshold of the perturbation
      electrode (-2 dB re threshold). Measurements were first conducted for
      simultaneous stimulation of the probe and of the perturbation electrodes, for
      monopolar for all subjects and for bipolar stimulus configurations for both
      Clarion HiFocus-I subjects. The tested Clarion electrodes did not present lower
      monopolar interactions than the Ineraid electrodes. Nevertheless, considering the
      shorter distance between electrodes for the Clarion than for the Ineraid, the
      tested Clarion electrodes might be more selective than the Ineraid. We did not
      find any significant monopolar electrical field-interaction differences between
      subjects who received the S-Series array with and without the EPS. We did not
      find lower interactions for both subjects who received the HiFocus-I array than
      for subjects who received the S-Series. Electrical field interactions were lower
      for bipolar than for monopolar configurations for both HiFocus-I subjects. A
      second set of measurements was conducted for nonsimultaneous stimulation similar
      to the one used in continuous interleaved sampling sound strategy. These
      measurements showed that interactions evaluated for simultaneous biphasic stimuli
      were larger than for nonsimultaneous stimulation.

PMID- 14587605
TI  - Forward masking in different cochlear implant systems.
AB  - The goal of this study was to evaluate, from a psychophysical standpoint, the
      neural spread of excitation produced by the stimulation of different types of
      intracochlear electrode arrays: the Ineraid, the Clarion S-Series on its own or
      with the Electrode Positioning System (EPS), and the Clarion HiFocus-I with the
      EPS. The EPS is an independent silicone part designed to bring the electrode
      array close to the modiolus. Forward masking was evaluated in 12 adult subjects
      (3 Ineraid, 4 Clarion S-Series, 3 Clarion S-Series+EPS, 3 HiFocus-I+EPS) by
      psychophysical experiments conducted using trains of biphasic stimuli (813 pulses
      per second, 307.6 micros/phase). Masker signals (+8 dB re: threshold, 300 ms)
      were applied to the most apical electrode. Probe signals (30 ms, 10-ms
      postmasker) were delivered to more basal electrodes. Masked and unmasked
      detection thresholds of probe signals were measured. For both Clarion HiFocus-I
      subjects, measurements were conducted in both monopolar and bipolar stimulus
      configurations. No major differences were found in forward masking between the
      different intracochlear electrode arrays tested in the monopolar configuration at
      suprathreshold levels equivalent to those used in speech-coding strategies, but
      significant differences were found between subjects. A significant negative
      correlation also was found between the level of forward masking and the consonant
      identification performance. These measurements showed that the neural spread of
      excitation was more restricted in the bipolar configuration than in the monopolar
      configuration for HiFocus-I subjects. It was found that CIS strategies
      implemented without using apical electrodes, which showed high levels of masking,
      could improve consonant identification.

PMID- 14587606
TI  - Desynchronization of electrically evoked auditory-nerve activity by high
      frequency pulse trains of long duration.
AB  - Rubinstein et al. [Hear. Res. 127, 108-118 (1999)] suggested that the neural
      representation of the waveforms of electric stimuli might be improved by
      introducing an ongoing, high-rate, desynchronizing pulse train (DPT). A DPT may
      desynchronize neural responses to electric stimulation in a manner similar to
      spontaneous activity in a healthy ear. To test this hypothesis, responses of
      auditory-nerve fibers (ANFs) to 10-min-long electric pulse trains (5 kpps) were
      recorded from acutely deafened, anesthetized cats. Stimuli were delivered via an
      intracochlear electrode, and their amplitude was chosen to elicit a response in
      most ANFs. Responses to pulse trains showed pronounced adaptation during the
      first 1-2 min, followed by either a sustained response or cessation of spike
      discharges for the remainder of the stimulus. The adapted discharge rates showed
      a broad distribution across the ANF population like spontaneous activity.
      However, a higher proportion of fibers (46%) responded to the DPT at rates below
      5 spikes/s than for spontaneous activity, and 12% of the fibers responded at
      higher rates than any spontaneously active fiber. Interspike interval histograms
      of sustained responses for some fibers had Poisson-like (exponential) shapes,
      resembling spontaneous activity, while others exhibited preferred intervals and,
      occasionally, bursting. Simultaneous recordings from pairs of fibers revealed no
      evidence of correlated activity, suggesting that the DPT does desynchronize the
      auditory nerve activity. Overall, these results suggest that responses to an
      ongoing DPT resemble spontaneous activity in a normal ear for a substantial
      fraction of the ANFs.

PMID- 14587607
TI  - Improved temporal coding of sinusoids in electric stimulation of the auditory
      nerve using desynchronizing pulse trains.
AB  - Rubinstein et al. [Hearing Res. 127, 108-118 (1999)] suggested that the
      representation of electric stimulus waveforms in the temporal discharge patterns
      of auditory-nerve fiber (ANF) might be improved by introducing an ongoing, high
      rate, desynchronizing pulse train (DPT). To test this hypothesis, activity of
      ANFs was studied in acutely deafened, anesthetized cats in response to 10-min
      long, 5-kpps electric pulse trains that were sinusoidally modulated for 400 ms
      every second. Two classes of responses to sinusoidal modulations of the DPT were
      observed. Fibers that only responded transiently to the unmodulated DPT showed
      hyper synchronization and narrow dynamic ranges to sinusoidal modulators, much as
      responses to electric sinusoids presented without a DPT. In contrast, fibers that
      exhibited sustained responses to the DPT were sensitive to modulation depths as
      low as 0.25% for a modulation frequency of 417 Hz. Over a 20-dB range of
      modulation depths, responses of these fibers resembled responses to tones in a
      healthy ear in both discharge rate and synchronization index. This range is much
      wider than the dynamic range typically found with electrical stimulation without
      a DPT, and comparable to the dynamic range for acoustic stimulation. These
      results suggest that a stimulation strategy that uses small signals superimposed
      upon a large DPT to encode sounds may evoke temporal discharge patterns in some
      ANFs that resemble responses to sound in a healthy ear.

PMID- 14587609
TI  - An approximate transfer function for the dual-resonance nonlinear filter model of
      auditory frequency selectivity.
AB  - The dual-resonance nonlinear filter [Meddis et al., J. Acoust. Soc. Am. 109, 2852
      2861 (2001)] was presented as a digital time-domain algorithm to model nonlinear
      auditory frequency selectivity. This report extends previous work by presenting
      an approximate analytic transfer function that allows calculating and analyzing
      its level-dependent frequency-domain response. The transfer function is derived
      on the assumption that the filter behaves linearly for any given input amplitude.
      It matches accurately the response (gain and phase) of the digital filter for
      tones. Practical uses for the transfer function are suggested.

PMID- 14587610
TI  - Spectral pattern, harmonic relations, and the perceptual grouping of low-numbered
      components.
AB  - Mistuning a harmonic increases its salience and produces an exaggerated change in
      its pitch. The effects on component grouping of spectral pattern, global pitch,
      and local harmonicity were explored using these phenomena. Stimuli were either
      harmonic (F0 = 200 Hz) or frequency shifted by 25% of F0. Component 1 or 2 was
      replaced by one of a set of sinusoidal probes in the same spectral region.
      Listeners either matched the probe pitch by adjusting the frequency of a pure
      tone (experiments 1 and 3) or matched the probe loudness by adjusting the level
      of a tone of identical frequency (experiment 2). Probe positions corresponding to
      greatest perceptual fusion were estimated from the variations in pitch shift and
      loudness across frequency. Both measures gave similar estimates. For harmonic
      stimuli, fusion was greatest at harmonic values. For shifted stimuli, fusion was
      greatest close to the suboctave (225 Hz) and the frequency (450 Hz) of component
      2. The latter value moved downwards to near 433 Hz (2:3 ratio with component 3)
      when component 1 was removed. Together, these results indicate that the lowest
      component of a shifted complex is grouped by local harmonicity, whereas the
      higher components are grouped by common spectral spacing. Global pitch did not
      influence component grouping.

PMID- 14587608
TI  - Improved neural representation of vowels in electric stimulation using
      desynchronizing pulse trains.
AB  - Current cochlear implant processors poorly represent sound waveforms in the
      temporal discharge patterns of auditory-nerve fibers (ANFs). A previous study
      [Litvak et al., J. Acoust. Soc. Am. 114, 2079-2098 (2003)] showed that the
      temporal representation of sinusoidal stimuli can be improved in a majority of
      ANFs by encoding the stimuli as small modulations of a sustained, high-rate (5
      kpps), desynchronizing pulse train (DPT). Here, these findings are extended to
      more complex stimuli by recording ANF responses to pulse trains modulated by
      bandpass filtered vowels. Responses to vowel modulators depended strongly on the
      discharge pattern evoked by the unmodulated DPT. ANFs that gave sustained
      responses to the DPT had period histograms that resembled the modulator waveform
      for low (< 5%) modulation depths. Spectra of period histograms contained peaks
      near the formant frequencies. In contrast, ANFs that gave a transient (< 1 min)
      response to the DPT poorly represented the formant frequencies. A model
      incorporating a linear modulation filter, a noisy threshold, and neural
      refractoriness predicts the shapes of period histograms for both types of fibers.
      These results suggest that a DPT-enhanced strategy may achieve good
      representation of the stimulus fine structure in the temporal discharge patterns
      of ANFs for frequencies up to 1000 Hz. It remains to be seen whether these
      temporal discharge patterns can be utilized by cochlear implant subjects.

PMID- 14587611
TI  - Modulation masking produced by complex tone modulators.
AB  - Thresholds were measured for detecting sinusoidal amplitude modulation in the
      presence of a complex-tone masker modulation. Both modulations were applied to
      the same sinusoidal carrier. Two different masker modulations were used: (i) a
      pair of components beating at the difference frequency and (ii) a three-tone
      complex producing a sinusoidal amplitude modulation of the modulation depth at
      the difference frequency between adjacent components. Both maskers show a
      periodicity in the waveform that is not contained in the envelope spectrum itself
      but can be observed when the envelope of the envelope, referred to as the
      "venelope" [Ewert et al., J. Acoust. Soc. Am. 112, 2921-2931 (2002)], is
      calculated. For a signal frequency equal to the masker-venelope periodicity,
      modulation depth at threshold was measured as a function of the signal phase
      relative to the phase of the masker-venelope component. Signal frequencies of 5,
      30, and 90 Hz were used. It was found that masking was phase dependent for all
      three signal frequencies. Thresholds were lower for the in-phase condition, where
      maxima in the signal waveform coincided with maxima in the masker-venelope
      waveform, than for the antiphase condition. The maximum threshold difference was
      15 dB. The results are in contrast to recent data [Moore et al., J. Acoust. Soc.
      Am. 106, 908-918 (1999)], where lowest thresholds were reported for the antiphase
      condition in a similar experiment. The present data are in line with the idea
      that a nonlinearity prior to a modulation filterbank extracts the venelope of the
      masker modulator. However, a compressive nonlinearity such as that associated
      with the processing on the basilar membrane cannot account for the empirical
      findings, since it predicts the opposite phase effect.

PMID- 14587613
TI  - Phase effects in masking: within- versus across-channel processes.
AB  - The effects of bandwidth and component phase on masking were investigated using
      200-ms narrowband (1-ERB(N)) and broadband (5-ERB(N)) cosine-phase (CP) and
      random-phase (RP) harmonic complex maskers, centered at 1 or 6 kHz. A continuous
      notched-noise was used to restrict off-frequency listening. The masker
      fundamental frequency (F0) was 25 Hz. In experiment 1, thresholds were measured
      for sinusoidal signals at 1 and 6 kHz, gated with the maskers. Thresholds were
      lower in the CP than in the RP masker, for both bandwidths, but the effect was
      markedly greater for the wider bandwidth. For the CP maskers, thresholds were
      markedly lower for the 5-ERB(N) than for the 1-ERB(N) bandwidth; for the RP
      maskers, there was a small effect in the opposite direction. Experiment 2 used 1-
      and 6-kHz CP maskers. The masker components in the ERB(N) around the signal
      frequency were presented to one ear, and the remaining components were presented
      contralaterally. Thresholds were much higher than when all components were
      presented to the same ear, and were higher than for the 1-ERB(N) masker alone,
      suggesting that the low thresholds for broadband monaural presentation do not
      depend on "high level" across-channel comparisons. Simultaneous masked thresholds
      could be predicted well using a model based on a simulated auditory filter, a
      level-dependent compressive nonlinearity, and a sliding temporal integrator; it
      was not necessary to assume the involvement of across-channel processes or of
      selective listening in the masker dips.

PMID- 14587612
TI  - A measure of internal noise based on sample discrimination.
AB  - Internal noise is often inferred from the difference between observed performance
      and optimum performance in detection and discrimination tasks. It can be measured
      directly in some cases by observing the extent to which a change in external
      variability impacts performance. In the studies reported here, external
      variability was added to an intensity discrimination task by adding a Gaussian
      random variable with zero mean to the overall level presented in each interval of
      a two-interval forced-choice task. The standard deviation of the random variable
      was set to half the mean difference between the levels in the two intervals,
      resulting in d'(ideal) = 2. As the mean difference and the corresponding standard
      deviation of the random variable decreased in size, performance was increasingly
      limited by internal noise, permitting a reliable estimate of internal noise to be
      obtained. This can be viewed as a sample discrimination task, with one component
      per sample. In the first study, performance was measured using 2-kHz tones
      presented at an average level of 70 dB SPL, with mean differences between
      distributions ranging from 0.1 to 2.2 dB in steps of 0.3 dB. The distributions
      were either Gaussian in level or in power. Conditions with no external
      variability were used to obtain a psychometric function. In the second study,
      performance was measured using 2-kHz tones presented at average levels of 50 and
      90 dB SPL, with mean differences ranging from 0.4 to 2.2 dB in steps of 0.6 dB.
      In both studies, the measure of internal noise was highly reliable and in good
      agreement with the intensity difference limen (DL) estimated from the
      psychometric function. Analyses suggest that this measure could be used to
      estimate the mean difference between the decision distributions as well as the
      amount of internal noise in cases where the mean difference between the
      distributions is unknown.

PMID- 14587614
TI  - Threshold differences for interaural time delays carried by double vowels.
AB  - Experimental measurements were made of threshold interaural time differences
      (ITDs) for a "target" vowel presented simultaneously with a fixed-ITD
      "distracter" vowel. Three double-vowel pairs were used, comprising an "er" (/e/)
      together with either an "ai," "ar," or "oo" (respectively, /e/, /c/, and /u/).
      Threshold ITDs were found to be larger for the target vowel when it was part of a
      double-vowel pair than in control conditions in which it was presented alone. The
      effect size depended upon the choice of target vowel and distracter vowel, the
      level of the target relative to the distracter, and whether the two vowels had
      the same or different fundamental frequencies. The experiment was analyzed using
      a multichannel modification of Heller and Trahiotis' [J. Acoust. Soc. Am. 99,
      3632-3637 (1996)] model, which used a weighted combination of the detectabilities
      of the ITD of the target and the distracter. It gave predictions consistent with
      the observed effects of level and with some of the effects of the choice of
      target vowel, but it could not describe the effect of the target-distracter
      differences in fundamental frequency. It was found that a single-channel version
      of the model, in which the chosen channel was allowed to depend upon fundamental
      frequency (which could be derived using a monaural autocorrelation model) did
      give a set of predictions in qualitative accord with the data.

PMID- 14587615
TI  - Perceptual segregation of competing speech sounds: the role of spatial location.
AB  - Culling and Summerfield [J. Acoust Soc. Am. 92, 785-797 (1995)] showed that
      listeners could not use ongoing interaural time differences (ITDs) to achieve
      source segregation. The present experiments tested a free-field analog of their
      experiment. The stimuli consisted of narrow bands of noise, pairs of which
      represented the first and second formants of the whispered vowels "ar," "ee,"
      "er," and "oo." A target noise-band pair (vowel) was presented at various angles
      on the listeners' left while a complementary distracter was presented on the
      listeners' right. Listeners correctly identified the target vowel in the free
      field well above chance. Performance remained well above chance in headphone
      experiments that retained spatial cues but eliminated reverberations and head
      movements. The full range of cues that normally determine perceived spatial
      location provided sufficient information for segregation. Further experiments,
      which systematically evaluated the contribution of these cues in isolation and in
      combination, showed that some listeners, following training, exhibited the
      ability to segregate based on ongoing ITDs alone. Substantial individual
      differences were observed. The results show that listeners can use spatial cues
      to segregate simultaneous sound sources.

PMID- 14587616
TI  - Application of loudness models to sound processing for cochlear implants.
AB  - A new paradigm for processing sound signals for multiple-electrode cochlear
      implants is introduced, and results are presented from an initial psychophysical
      evaluation of its effect on the perceived loudness of complex sounds. A real-time
      processing scheme based on this paradigm, called SpeL, has been developed
      primarily to improve control of loudness for implant users. SpeL differs from
      previous schemes in several ways. Most importantly, it incorporates a published
      numerical model which predicts the loudness perceived by implant users for
      complex patterns of pulsatile electric stimulation as a function of the pulses'
      physical parameters. This model is controlled by the output of a corresponding
      model that estimates the loudness perceived by normally hearing listeners for
      complex sounds. The latter model produces an estimate of the specific loudness
      arising from an acoustic signal. In SpeL, the specific loudness function, which
      describes the contribution to total loudness of each of a number of frequency
      bands (or cochlear positions), is converted to a pattern of electric stimulation
      on an appropriate set of electrodes. By application of the loudness model for
      electric stimulation, this pattern is designed to produce a specific loudness
      function for the implant user which approximates that produced by the normal
      hearing model for the same input signal. The results of loudness magnitude
      estimation experiments with five users of the SpeL scheme confirmed that the
      psychophysical functions relating overall loudness perceived to input sound level
      for five complex acoustic signals were, on average, very similar to those for
      normal hearing.

PMID- 14587617
TI  - Nonlinear dynamics of phonations in excised larynx experiments.
AB  - Nonlinear dynamic methods including correlation dimension and Lyapunov exponents
      are applied to quantitatively analyze phonations in excised larynx experiments.
      Irregular phonations are typically characterized by aperiodic waveforms and
      broadband spectra. Finite correlation dimensions and positive Lyapunov exponents
      of irregular phonations demonstrate the existence of chaos in excised larynx
      phonations. Furthermore, the correlation dimension, maximal Lyapunov exponent,
      jitter, shimmer, and peak prominence ratio are used to statistically distinguish
      irregular phonations from normal phonations. The correlation dimension and
      maximal Lyapunov exponent indicate a significant difference between irregular and
      normal phonations; however, jitter, shimmer, and peak prominence ratio do not
      reveal such a significant difference and thus are unsuitable to differentiate
      between irregular phonations and normal phonations. These findings might
      potentially assist investigators in understanding rough phonations and developing
      clinically valuable methodologies for the diagnosis of voice disorders.

PMID- 14587618
TI  - A quasi-glottogram signal.
AB  - A novel, noninvasive experiment is proposed that reliably shows the strength of
      glottal oscillations. The quasi-glottogram (QGG) signal is generated from a
      microphone array that is trained to approximate the electroglottogram signal. The
      QGG may be useful to improve estimates of whether speech is voiced, to quantify
      partial voicing, and to reduce the phoneme effect when measuring the amplitude of
      speech signals. The technique is well adapted to the generation of text-to-speech
      systems, as it allows an estimate of the glottal flow during undisturbed, natural
      speech. For prosody studies, it can be used to provide an estimate of amplitude
      which is relatively unaffected by changes in phonemes, and is at least as
      reliable as standard estimators of amplitude.

PMID- 14587619
TI  - Objective measures of breathy voice quality obtained using an auditory model.
AB  - While several acoustic measures have been proposed to quantify listener ratings
      of breathy voice quality, most have failed to give a consistent and high
      correlation with perceptual ratings of breathiness. One reason for these
      limitations is that most acoustic measures do not address the nonlinear processes
      that occur in the peripheral auditory system during the auditory perceptual
      process. It was hypothesized that modeling such nonlinear events during signal
      processing may provide objective parameters that better correspond to perceptual
      ratings of breathy voice quality. Ten listeners rated 27 voice stimuli using a
      five-point rating scale. Acoustic measures were determined from these stimuli and
      were selected based on their history of having a moderate to strong correlation
      to perceptual ratings of breathiness. The stimuli were also analyzed using an
      auditory model proposed by Moore, Glasberg, and Baer [J. Audio Eng. Soc. 45(4),
      224-239 (1997)], and new measures were calculated from the output of this model.
      These measures included the partial loudness of the signal and the loudness of
      the aspiration noise. Measures obtained from the output of the auditory model
      were found to account for a high amount of variance in the perceptual ratings of
      breathiness.

PMID- 14587621
TI  - Speech segregation based on sound localization.
AB  - At a cocktail party, one can selectively attend to a single voice and filter out
      all the other acoustical interferences. How to simulate this perceptual ability
      remains a great challenge. This paper describes a novel, supervised learning
      approach to speech segregation, in which a target speech signal is separated from
      interfering sounds using spatial localization cues: interaural time differences
      (ITD) and interaural intensity differences (IID). Motivated by the auditory
      masking effect, the notion of an "ideal" time-frequency binary mask is suggested,
      which selects the target if it is stronger than the interference in a local time
      frequency (T-F) unit. It is observed that within a narrow frequency band,
      modifications to the relative strength of the target source with respect to the
      interference trigger systematic changes for estimated ITD and IID. For a given
      spatial configuration, this interaction produces characteristic clustering in the
      binaural feature space. Consequently, pattern classification is performed in
      order to estimate ideal binary masks. A systematic evaluation in terms of signal
      to-noise ratio as well as automatic speech recognition performance shows that the
      resulting system produces masks very close to ideal binary ones. A quantitative
      comparison shows that the model yields significant improvement in performance
      over an existing approach. Furthermore, under certain conditions the model
      produces large speech intelligibility improvements with normal listeners.

PMID- 14587620
TI  - Effects of contrast between onsets of speech and other complex spectra.
AB  - Previous studies using speech and nonspeech analogs have shown that auditory
      mechanisms which serve to enhance spectral contrast contribute to perception of
      coarticulated speech for which spectral properties assimilate over time. In order
      to better understand the nature of contrastive auditory processes, a series of CV
      syllables varying acoustically in F2-onset frequency and perceptually from /ba/
      to /da/ was identified following a variety of spectra including three-peak
      renditions of [e] and [o], one-peak simulations of only F2, and spectral
      complements of these spectra for which peaks are replaced with troughs. Results
      for three-versus one-peak (or trough) precursor spectra were practically
      indistinguishable, suggesting that effects were spectrally local and not
      dependent upon perception of precursors as speech. Effects of complementary
      (trough) spectra had complementary effects on perception of following stops;
      however, effects for spectral complements were particularly dependent upon the
      interval between precursor and CV onsets. Results from these studies cannot be
      explained by simple masking or adaptation of suppression. Instead, they provide
      evidence for the existence of processes that selectively enhance contrast between
      onset spectra of neighboring sounds, and these processes are relevant for
      perception of connected speech.

PMID- 14587622
TI  - Nonlinear characteristics of single-reed instruments: quasistatic volume flow and
      reed opening measurements.
AB  - A wind instrument can be described as a closed feedback loop made up of a linear
      passive element-the resonator-and a lumped nonlinear element-the mouthpiece. A
      method for measuring the nonlinear characteristics of the mouthpiece-nonlinear
      flow relationship-in static condition is given. An artificial mouth is used in
      which the volume flow is deduced from the pressure difference between both sides
      of a constriction (orifice) which takes place in the resonator. The orifice also
      plays the role of a nonlinear absorber, thwarting possible reed oscillations.
      This allows the measurement of the complete characteristics. In addition, the
      reed opening is measured using an optical device. Results are compared to a model
      in which the reed is reduced to its stiffness and the flow is governed by the
      Bernoulli equation. It is shown that the reed stiffness and the ratio of the
      effective surface of the jet and the reed opening are constant in a large range
      of openings. Standard range values of embouchure parameters are given.

PMID- 14587623
TI  - Cutoff frequencies and cross fingerings in baroque, classical, and modern flutes.
AB  - Baroque, classical, and modern flutes have successively more and larger tone
      holes. This paper reports measurements of the standing waves in the bores of
      instruments representing these three classes. It presents the frequency
      dependence of propagation of standing waves in lattices of open tone holes and
      compares these measurements with the cutoff frequency: the frequency at which, in
      an idealized system, the standing waves propagate without loss in such a lattice.
      It also reports the dependence of the sound field in the bore of the instrument
      as a function of both frequency and position along the bore for both simple and
      "cross fingerings" (configurations in which one or more tone holes are closed
      below an open hole). These measurements show how "cross fingerings" produce a
      longer standing wave, a technique used to produce the nondiatonic notes on
      instruments with a small number of tone holes closed only by the unaided fingers.
      They also show why the changes from baroque to classical to modern gave the
      instruments a louder, brighter sound and a greater range.

PMID- 14587624
TI  - Measurement and reproduction accuracy of computer-controlled grand pianos.
AB  - The recording and reproducing capabilities of a Yamaha Disklavier grand piano and
      a Bosendorfer SE290 computer-controlled grand piano were tested, with the goal of
      examining their reliability for performance research. An experimental setup
      consisting of accelerometers and a calibrated microphone was used to capture key
      and hammer movements, as well as the acoustic signal. Five selected keys were
      played by pianists with two types of touch ("staccato" and "legato"). Timing and
      dynamic differences between the original performance, the corresponding MIDI file
      recorded by the computer-controlled pianos, and its reproduction were analyzed.
      The two devices performed quite differently with respect to timing and dynamic
      accuracy. The Disklavier's onset capturing was slightly more precise (+/- 10 ms)
      than its reproduction (-20 to +30 ms); the Bosendorfer performed generally
      better, but its timing accuracy was slightly less precise for recording (-10 to 3
      ms) than for reproduction (+/- 2 ms). Both devices exhibited a systematic
      (linear) error in recording over time. In the dynamic dimension, the Bosendorfer
      showed higher consistency over the whole dynamic range, while the Disklavier
      performed well only in a wide middle range. Neither device was able to capture or
      reproduce different types of touch.

PMID- 14587625
TI  - Acoustic wave propagation in bovine cancellous bone: application of the Modified
      Biot-Attenborough model.
AB  - Acoustic wave propagation in bovine cancellous bone is experimentally and
      theoretically investigated in the frequency range of 0.5-1 MHz. The phase
      velocity, attenuation coefficient, and broadband ultrasonic attenuation (BUA) of
      bovine cancellous bone are measured as functions of frequency and porosity. For
      theoretical estimation, the Modified Biot-Attenborough (MBA) model is employed
      with three new phenomenological parameters: the boundary condition, phase
      velocity, and impedance parameters. The MBA model is based on the idealization of
      cancellous bone as a nonrigid porous medium with circular cylindrical pores
      oriented normal to the surface. It is experimentally observed that the phase
      velocity is approximately nondispersive and the attenuation coefficient linearly
      increases with frequency. The MBA model predicts a slightly negative dispersion
      of phase velocity linearly with frequency and the nonlinear relationships of
      attenuation and BUA with porosity. The experimental results are in good agreement
      with the theoretical results estimated with the MBA model. It is expected that
      the MBA model can be usefully employed in the field of clinical bone assessment
      for the diagnosis of osteoporosis.

PMID- 14587626
TI  - Functional lung imaging: emerging methods to visualize regional pulmonary
      physiology.

PMID- 14587627
TI  - Voxelwise mapping of magnetic resonance ventilation-perfusion ratio in a porcine
      model by multimodality registration: technical note.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to demonstrate the
      construction of voxelwise ventilation-perfusion (V/Q) ratio maps in a porcine
      model by nonrigidly aligning the respective ventilation and perfusion images
      using a multimodality registration algorithm. MATERIALS AND METHODS: The first
      pass contrast agent technique for a blood flow map and 3He used for ventilation
      imaging were performed using a normal porcine model. The registered 3He
      ventilation image was then aligned to the blood flow map using a multimodality
      registration algorithm. The voxelwise V/Q ratios were calculated by dividing the
      registered 3He-ventilation image by the blood flow map. The V/Q ratios were also
      semi-logarithmically scatter-plotted against the number of voxels. RESULTS: From
      perfusion magnetic resonance images, a voxel-by-voxel blood flow map was
      produced. Registered 3He ventilation image was successfully obtained as well as
      V/Q ratio map. Plots of the V/Q ratios obtained by this registration approach
      were similar to the logarithmic normal distribution. CONCLUSION: Registration of
      MR perfusion and ventilation images can potentially enable quantitative
      evaluation of regional pulmonary function and thus yield deeper insight into the
      physiology and pathophysiology of the lung.

PMID- 14587628
TI  - Airway distension with lung inflation measured by HRCT.

PMID- 14587629
TI  - Characterization of the interstitial lung diseases via density-based and texture
      based analysis of computed tomography images of lung structure and function.
AB  - RATIONALE AND OBJECTIVES: Efforts to establish a quantitative approach to the
      computed tomography (CT)-based character ization of the lung parenchyma in
      interstitial lung disease (including emphysema) has been sought. The accuracy of
      these tools must be site independent. Multi-detector row CT has remained the gold
      standard for imaging the lung, and it provides the ability to image both lung
      structure as well as lung function. MATERIAL AND METHODS: Imaging is via multi
      detector row CT and protocols include careful control of lung volume during
      scanning. Characterization includes not only anatomic-based measures but also
      functional measures including regional parameters derived from measures of
      pulmonary blood flow and ventilation. Image processing includes the automated
      detection of the lungs, lobes, and airways. The airways provide the road map to
      the lung parenchyma. Software automatically detects the airways, the airway
      centerlines, and the branch points, and then automatically labels the airway tree
      segments with a standardized set of labels, allowing for intersubject as well
      intrasubject comparisons across time. By warping all lungs to a common atlas, the
      atlas provides the range of normality for the various parameters provided by CT
      imaging. RESULTS: Imaged density and textural changes mark underlying structural
      changes at the most peripheral regions of the lung. Additionally, texture-based
      alterations in the parameters of blood flow may provide early evidence of
      pathologic processes. Imaging of stable xenon gas provides a regional measure of
      ventilation which, when coupled with measures of flow, provide for a textural
      analysis regional of ventilation-perfusion matching. CONCLUSION: With the
      improved resolution and speed of CT imaging, the patchy nature of regional
      parenchymal pathology can be imaged as texture of structure and function. With
      careful control of imaging protocols and the use of objective image analysis
      methods it is possible to provide site-independent tools for the assessment of
      interstitial lung disease. There remains a need to validate these methods, which
      requires interdisciplinary and cross-institutional efforts to gather appropriate
      data bases of images along with a consensus on appropriate ground truths
      associated with the images. Furthermore, there is the growing need for scanner
      manufacturers to focus on not just visually pleasing images, but on
      quantitatifiably accurate images.

PMID- 14587630
TI  - Magnetic resonance imaging using hyperpolarized 3He-Gas.
AB  - RATIONALE AND OBJECTIVES: Current imaging procedures of the lung concentrate on
      visualization of morphology. Computed tomography is the imaging method of choice
      for the majority of pulmonary diseases. Functional data are commonly obtained
      from arterial blood gas analysis, spirometry, and body plethysmography, which all
      suffer from lack of regional information. MATERIALS AND METHODS: Magnetic
      resonance imaging (MRI) of the lung has been advanced recently by the use of
      hyperpolarized 3He as a new contrast mechanism. Four different image acquisition
      modes are performed during a typical patient study. RESULTS: 3He-MRI yields
      functional information about the lung with a high spatial and temporal
      resolution, avoiding the risks of ionizing radiation. The method is currently
      limited by high costs and restricted availability of the gas. CONCLUSION: In this
      article, the experience obtained at the University of Mainz, being Europe's most
      experienced center performing 3He-MRI in humans, is reviewed against the
      international background.

PMID- 14587631
TI  - CT perfusion imaging of the lung in pulmonary embolism.

PMID- 14587632
TI  - Characterization of regional pulmonary mechanics from serial magnetic resonance
      imaging data.
AB  - RATIONALE AND OBJECTIVES: The aim of this study was to investigate a method for
      quantifying lung motion from the registration of successive images in serial
      magnetic resonance imaging acquisitions during normal respiration. MATERIALS AND
      METHODS: Estimates of pulmonary motion were obtained by summing the normalized
      cross-correlation over serially acquired lung images to identify corresponding
      locations between the images. The estimated motions were modeled as deformations
      of an elastic body and thus reflect to a first order approximation the true
      physical behavior of lung parenchyma. The Lagrangian strain, derived from the
      calculated motion fields, were used to quantify the tissue deformation induced in
      the lung over the serial acquisition. RESULTS: The method was validated on a
      magnetic resonance imaging study, for which breath-hold images were acquired of a
      healthy volunteer at different phases of the respiratory cycle. Regional
      parenchymal strain was observed to be oriented toward the pulmonary hilum, with
      strain magnitude maximal at the midcycle of the expiratory phase. CONCLUSION: In
      vivo magnetic resonance imaging quantification of lung motion holds the potential
      of providing a new diagnostic dimension in the assessment of pulmonary function,
      augmenting the information provided by studies of ventilation and perfusion.

PMID- 14587633
TI  - High-resolution Micro-CT evaluation of mid- to long-term effects of estrogen
      deficiency on rat trabecular bone.
AB  - RATIONALE AND OBJECTIVES: Previous studies have shown dramatic short-term bone
      loss following ovariectomy. The purpose of this study was to evaluate mid- to
      long-term effects of estrogen deficiency on microarchitecture of tibial
      trabecular bone using a high-resolution microcomputed tomography (Micro-CT).
      MATERIALS AND METHODS: Twenty-eight female rats were divided into two equal
      groups: ovariectomized (OVX, n = 14) and sham-operated (SOVX, n = 14), which in
      turn were divided into two equal subgroups (euthanized either 6 or 16 weeks after
      surgery). The left tibia of each animal was scanned with a high-resolution micro
      CT (Skyscan 1072 micro-CT system; SkyScan, Aartselaar, Belgium). The Micro-CT
      system used an X-ray CCD-camera with a cooled 1024 x 1024-pixel 12-bit sensor.
      RESULTS: Ovariectomy significantly decreased the ratio of bone volume:tissue
      volume (-42% at 6 weeks and -69% at 16 weeks) and trabecular thickness (-13% at 6
      weeks and -30% at 16 weeks), while significantly increasing trabecular separation
      (+73% at 6 weeks and +100% at 16 weeks) and structure model index (+15% at 6
      weeks and +48% at 16 weeks), when compared with SOVX, from 6 to 16 weeks.
      CONCLUSION: Based on the experimental results, there are alterations of
      trabecular microarcihtecture in the tibia following mid- and long-term estrogen
      deficiency. More rod-shaped trabeculae are formed with increasing duration of
      estrogen deficiency. The high-resolution micro-CT imaging system is useful to
      evaluate the mid- to long-term trabecular changes seen with estrogen deficiency
      or osteoporosis.

PMID- 14587634
TI  - Near-infrared fluorescence imaging of microcalcification in an animal model of
      breast cancer.
AB  - RATIONALE AND OBJECTIVES: At present, there is no animal model of breast cancer
      that forms reproducible microcalcification. The aim of this study was to develop
      a straightforward, reproducible model system that could be used to develop
      multimodality contrast agents for the identification of breast cancer
      microcalcification. METHODS: The R3230 mammary adenocarcinoma cell line was
      implanted in the mammary fat pad of female Fischer 344 rats (two rats with two
      implanted tumors and two rats with a single implanted tumor). After growth to 1-2
      cm in diameter, tumors were implanted with 100 microm hydroxyapatite crystals
      (positive control) or calcium oxalate crystals (negative control). Twenty-four
      hours after crystal implantation, rats were injected intravenously with a
      previously described near-infrared fluorescent bisphosphonate derivative known as
      Pam78, and the tumors were imaged using a reflectance optical imaging system.
      RESULTS: Tumors implanted with hydroxyapatite displayed bright, focal, near
      infrared fluorescence in the area of crystal implantation. Control tumors, grown
      in the same animal and implanted with calcium oxalate, did not display any near
      infrared fluorescence, even along the needle track used for crystal implantation.
      CONCLUSIONS: A simple and rapid animal model of focal calcification in breast
      cancer tumors has been developed and validated. The model used Pam78, a near
      infrared fluorescent contrast agent specific for hydroxyapatite. The potential
      usefulness of the model for developing similar contrast agents for magnetic
      resonance and other imaging modalities is discussed.

PMID- 14587635
TI  - Comparing genomic and histologic correlations to radiographic changes in tumors:
      a murine SCC VII model study.
AB  - RATIONALE AND OBJECTIVES: To investigate the correlation between the temporal
      changes in T1- and T2-weighted contrast-enhanced magnetic resonance imaging
      (MRI), histologic evaluation, and genomic analysis using oligonucleotide
      microarrays in a murine squamous cell carcinoma tumor models. MATERIALS AND
      METHODS: The squamous cell carcinoma (SCC VII) cell line was used to initiate
      subcutaneous tumors in mice. This mouse model has been used as a model for human
      head and neck carcinomas. Animals were imaged using contrast enhanced MRI (CE
      MRI). Different stages of tumor growth were defined based on changes in the T1-
      and T2-weighted MRI patterns. The contrast enhancing (CE) and nonenhancing (NE)
      regions of the tumors were marked and biopsied for oligonucleotide microarray and
      histologic analysis. Tumors with no differential contrast enhancement were used
      as controls. RESULTS: Distinct temporal stages of tumor progression can be
      defined using both T1- and T2-weighted CE-MRI and microarray analysis. The early
      stage tumors show a homogeneous contrast enhancement pattern in the T1- and T2
      weighted images with no significant differential gene expression from the center
      and periphery of the tumor. The more advanced tumors that show discrete regions
      of contrast enhancement in the post-contrast T1-weighted MRIs and tissues from
      the CE and NE regions show distinctly differential gene expression profiles.
      Histologic analysis (hematoxylin-eosin stain) showed that the samples obtained
      from the periphery and center of the early stage tumors and the CE and NE regions
      from these more advanced tumors were similar. The gene expression profiles of
      late-stage tumors that showed changes in T2-weighted MRI signal intensity were
      consistent with tissue degradation in the NE region, which also showed
      characteristic signs of tissue necrosis in histologic analysis. CONCLUSION: These
      results show that temporal changes in T1- and T2-weighted CE-MRI are related to
      distinct gene expression profiles, and histologic analysis may not be sufficient
      to detect these detailed changes. As tumors progress, discrete regions of post
      contrast T1 enhancement are identified; these regions have distinct gene
      expression patterns despite similar histologic features. In late-stage tumors,
      regions of T2 signal changes are observed which correspond with tissue necrosis.

PMID- 14587636
TI  - An approach to multiple-reader, multiple-case receiver operating characteristic
      analysis: controversial--or subtle?

PMID- 14587637
TI  - Thoughts on the ZOM/BWC controversy.

PMID- 14587638
TI  - The lure of profit in academic medicine.

PMID- 14587639
TI  - Balancing mission and money in academic medicine.

PMID- 14587640
TI  - Usefulness of 1H MR spectroscopy in the evaluation of myocardial metabolism in
      patients with dilated idiopathic cardiomyopathy: pilot study.
AB  - RATIONALE AND OBJECTIVES: Primary dilated cardiomyopathy is a disease of unknown
      etiology, and it leads to severe heart failure. Abnormalities of the cardiac
      metabolism can play an important role in prognosis and influence the
      symptomatology in this group. The aim of this study was to assess cardiac
      metabolism using proton spectroscopy magnetic resonance (1H MRS) and to examine
      whether there is any correlation between cardiac metabolites and functional New
      York Heart Association (NYHA) class and left ventricular function parameters
      obtained in echocardiography. MATERIALS AND METHODS: Fifteen patients with
      documented idiopathic dilated cardiomyopathy and 12 healthy volunteers were
      examined. The study protocol included clinical examination, 12-lead
      electrocardiogram, two-dimensional echocardiogram, and 1H MRS with voxel
      localized at interventricular septum area. The contents of total creatine (CR)
      ie, creatine + phosphocreatine, lipids (LIP), lactates (LAC) and their ratios
      (CR1A, CR2A, CR1/H20, CR2/H20, CR2/CR1, LIPA, LIP/H20, LIP/CR1, LACA, LAC/H20,
      LAC/CR1) were examined. RESULTS: Patients with dilated cardiomyopathy had
      significantly lower levels of creatine CRIA (5.04 +/- 0.88 vs 5.94 +/- 1.15, P <
      .02) and ratios LIP/H20 (4.34 +/- 2.3 vs 15.46 +/- 20.39, P < .04) and LIP/CR1
      (24.49 +/- 21.26 vs 34.08 +/- 13.36, P < .05) compared with healthy volunteers.
      Significant correlations between NYHA functional class and the ratios CR2/CR1,
      CR2/H20 (r = 0.59, P < .038, r = 0.59, P < .02, respectively) and between %LVEF
      and LIP/CR1 (r = 0.64, P < .036), as well as between the duration of the disease
      (TCH) and LIP/CR1 (r = 0.67, P < .046) were found. CONCLUSION: A pilot study with
      proton spectroscopy magnetic resonance showed impairment of the cardiac
      metabolism in patients with idiopathic dilated cardiomyopathy. A trend to lower
      values of creatine and lipids, and to lower ratios of some of these metabolites
      was observed in the dilated cardiomyopathy group compared with healthy subjects.
      The results require further study.

PMID- 14587641
TI  - C-reactive protein and immunoglobulin-E response to coronary artery stenting in
      patients with stable angina.
AB  - Recent reports indicate that inflammatory mechanisms play a crucial role in the
      pathogenesis of atherosclerosis and neointimal proliferation as well as coronary
      restenosis. To provide baseline data for further studies regarding stenting,
      restenosis and inflammatory response. we prospectively conducted a clinical study
      to investigate the time related response of plasma levels of immunoglobulin-E
      (IgE) and C-reactive protein (CRP) which are two different inflammatory markers
      mediated by different cytokines in stable patients who underwent elective
      coronary artery stenting. Thirteen consecutive stable patients who underwent
      coronary artery stenting were included in the study. Levels of IgE and CRP were
      determined pre- and poststent implantation on four consecutive days and at the
      end of the first as well as third month. Levels of these two markers were
      gradually elevated on postprocedure days while reaching peak values on the second
      and third days for IgE (initial 278 +/- 335 IU/mL vs peak 350 +/- 489 IU/mL, P =
      0.01) and CRP (initial 0.5 +/- 0 mg/dL vs peak 2.7 +/- 3 mg/dL, P = 0.002),
      respectively. High levels gradually returned to baseline values determined at the
      end of the first and even third months after stent implantation implying an acute
      inflammatory reaction. Stent implantation seems not to cause any persistent and
      ongoing inflammatory response in the long-term.

PMID- 14587642
TI  - Plasma levels of soluble thrombomodulin, C-reactive protein, and serum amyloid A
      protein in the atherosclerotic coronary circulation.
AB  - Plasma levels of C-reactive protein (CRP) and serum amyloid A protein (SAA),
      inflammatory markers, and soluble thrombomodulin (s-TM), a marker of endothelial
      damage. are thought to be related to coronary artery disease. However, the
      relationship between these inflammatory markers and endothelial injury in
      atherosclerotic coronary arteries is still unclear. Fifty-five patients who
      underwent coronary angiography were classified into 3 groups according to the
      severity of left coronary arterial atherosclerosis evaluated by the Gensini score
      (GS; normal: score = 0, n = 15; mild: 0 < score < 15, n = 29; severe: score > or
      = 15, n = 11). Blood samples were obtained from the aortic root (Ao) and coronary
      sinus (CS) and plasma CRP and SAA levels were measured by latex turbidimetric
      immunoassays, and s-TM levels were determined by an enzyme-linked immunosorbent
      assay. The difference between marker concentrations in the Ao and CS of the
      coronary circulation was expressed as the coronary sino-arterial (CS-Ao)
      difference. The CS-Ao differences of s-TM and SAA were significantly higher in
      patients with severe atherosclerosis than in normal patients (P < 0.01), and
      showed weak but significant positive correlations with the GS (r = 0.34, P < 0.01
      and r = 0.33, P < 0.05, respectively). The CS-Ao differences in CRP did not
      differ among the three groups, and did not correlate with the GS. The results of
      our study reveal a possible relationship between endothelial cell injury and
      inflammation in atherosclerotic coronary arteries.

PMID- 14587643
TI  - Association study of CD14 polymorphism with myocardial infarction in a Japanese
      population.
AB  - There have been many studies investigating the association between gene
      polymorphisms and coronary artery disease (CAD) including myocardial infarction
      (MI), and some studies have shown that certain gene polymorphisms are associated
      with CAD/MI. However, the results of the association have sometimes been
      controversial. The reason may be that the contribution of genetic risk factors to
      CAD/MI varies depending on the ethnic, environmental, and habitual backgrounds,
      and differs between males and females. In this study, we analyzed 17
      polymorphisms in 12 candidate genes for MI in 136 patients and 200 to 235
      controls, and found that there is a significant association of MI with the
      polymorphisms in the genes for E-selectin and CD14 receptor. To further explore
      the association, we investigated the C-260 T polymorphism in the promoter region
      of the CD14 gene in 502 MI patients and 527 control subjects. The genotype
      distributions of the CD14 polymorphism were as follows: patients; T/T 32.5%, C/T
      48.2%, C/C 19.3%, and controls; T/T 25.4%, C/T 52.8%, C/C 21.8%. The frequencies
      of the T/T homozygotes were significantly higher in the patients (OR = 1.41, P =
      0.013) than in the control group, confirming the association of CD14 polymorphism
      with MI in Japanese. Stratification analyses further demonstrated that the
      association was more prominent in females and in patients with a relatively low
      body mass index, suggesting that the contribution of the CD14-linked genetic risk
      to MI differs with respect to gender and habitual background.

PMID- 14587644
TI  - The prognostic value of IL-8 for cardiac events and restenosis in patients with
      coronary heart diseases after percutaneous coronary intervention.
AB  - The objective of the present study was to investigate the prognostic value of
      plasma interleukin-8 (IL-8) for adverse cardiac events and restenosis in patients
      with percutaneous coronary intervention (PCI). The pre- and post-procedural peak
      plasma levels of IL-8 and serum C-reactive protein (CRP) were examined by
      immunoassay, while adverse cardiae events and restenosis within one year follow
      up were observed in 134 consecutive patients who underwent PCI. Angiography
      revealed that 23.88% (32/134) of the patients had adverse cardiac events and
      29.41% (35/119) of the patients had restenosis. Preprocedural levels of IL-8 and
      CRP and post-procedural peak levels of IL-8 in patients with adverse cardiac
      events were higher than those without adverse cardiac events (all P < 0.05). The
      incidence of adverse cardiac events increased from 6.67% in the bottom tertile to
      31.82% in the top tertile of IL-8 levels (P = 0.001): a similar trend was
      observed for restenosis from 10% in low tertile to 51.28% in high tertile of IL-8
      levels to 51.8% (P = 0.012). The preprocedural levels of IL-8 (RR = 5.539, CI =
      1.720-17.887, P = 0.001) and CRP (RR = 2.031, CI = 1.132-2.049, P = 0.003) were
      the only independent predictors of adverse cardiac events. The post-procedure
      peak level of IL-8 (RR = 3.766, CI = 2.990-5.904, P = 0.002) and stent length (RR
      = 1.468, CI = 1.161-2.022. P = 0.021) were the independent predictors of
      restenosis. The results demonstrate that the release of IL-8 after PCI is a
      powerful prognostic factor for cardiac events and restenosis. The higher the peak
      level of post-procedure IL-8, the lower the event-free survival observed.

PMID- 14587645
TI  - Endothelin-1 concentrations in pericardial fluid are more elevated in patients
      with ischemic heart disease than in patients with nonischemic heart disease.
AB  - There is epidemiologic evidence that the prognosis of patients with nonischemic
      heart failure is better than that for patients with ischemic heart failure. In
      addition, studies have revealed that patients with ischemic heart failure show a
      poorer response to medical therapy. However, the pathophysiologic difference
      between ischemic and nonischemic heart disease is unclear. To clarify this point,
      we measured atrial natriuretic peptide, brain natriuretic peptide, angiotensin
      II, endothelin (ET)-1. interleukin-1beta interleukin-6. tumor necrosis factor
      (TNF)-alpha soluble TNF receptor I, and soluble TNF receptor II concentrations in
      plasma and pericardial fluid in patients with ischemic or nonischemic heart
      disease undergoing cardiac surgery. The pericardial ET-1 concentration in
      patients with ischemic heart disease was statistically greater than that in
      patients with nonischemic heart disease (about 1.5-fold), although no difference
      was found in the plasma ET-1 concentration. These findings suggest that the
      production and secretion of ET-1 from the myocardium in patients with ischemic
      heart disease are augmented to a greater extent than in patients with nonischemic
      heart disease. This result may lead to a greater understanding of the
      pathophysiology of ischemic heart disease.

PMID- 14587647
TI  - Noninvasive diagnosis of dual AV nodal physiology in patients with AV nodal
      reentrant tachycardia by adenosine triphosphate test.
AB  - Atrioventricular nodal reentrant tachycardia (AVNRT) is a relatively common
      paroxysmal supraventricular tachycardia. This study investigated whether
      adenosine-5'-triphosphate (ATP) injection during sinus rhythm might be useful in
      the noninvasive diagnosis of dual AV nodal pathways. The study group consisted of
      9 patients with slow/fast AVNRT and 11 control patients without antegrade dual AV
      nodal physiology (DAVNP). ATP (2.5 to 30 mg, in 2.5-mg increments was injected
      during sinus rhythm until signs of DAVNP (> or = 50 msec increase or decrease in
      AH or PR interval in two consecutive beats) or > or = second-degree AV block was
      observed. DAVNP was diagnosed by ATP test in all 9 patients with slow/fast AVNRT.
      DAVNP was observed by ATP test in 3 of the 11 control patients. Thus, the test
      had a sensitivity of 100% and specificity of 73%. ATP test given during sinus
      rhythm is useful for identifying patients with dual AV nodal pathways who are
      prone to AVNRT.

PMID- 14587648
TI  - Verapamil sensitive idiopathic ventricular tachycardia in an infant.
AB  - Idiopathic ventricular tachycardia is rare, especially in infants. We report here
      on an 8 month-old female infant who presented with tachycardia with a heart rate
      of 186 beats/ min. An electrocardiogram showed a right bundle branch block
      pattern, a QRS duration of 80 msec, a superior QRS axis, atrioventricular
      dissociation, and occasional fusion and capture beats. Suspected ventricular
      tachycardia was treated with lidocaine, propranolol and amiodarone, but in vain.
      The tachycardia was terminated and well controlled with the use of verapamil.
      According to an electrocardiogram and her clinical response, verapamil-sensitive
      idiopathic ventricular tachycardia was diagnosed with the arrhythmic origin in
      the left posterior fascicle.

PMID- 14587646
TI  - Diminished circadian rhythm of heart rate variability after aortic surgery
      appears to be independent of myocardial ischemia.
AB  - Impaired heart rate variability (HRV) has been described postoperatively.
      Diminished HRV may be related to myocardial ischemia and potentially causes
      circulatory instability. Cardiac ischemic events and a compromised cardiovascular
      function are not uncommon after aortic surgery. Circadian variation of HRV seems
      to be a prognostically more important parameter than HRV itself with respect to
      the development of cardiac dysfunction. We therefore investigated whether the
      diurnal rhythm of HRV is simultaneously altered postoperatively and the potential
      contribution of myocardial ischemia. After approval by the hospital ethics
      committee and having obtained informed consent, we studied 11 consecutive male
      patients undergoing elective aortic surgery. Patients were monitored with a
      Holter-ECG perioperatively. Spectral HRV measures (total, low, and high frequency
      power) were determined and night/day ratios calculated. Ischemic ECG changes were
      recorded and serum was sampled for troponin T analysis. A remarkable decline in
      circadian variation accompanied the decrease in all HRV parameters
      postoperatively. Five patients showed ECG changes suggestive of myocardial
      ischemia and two had increased levels of troponin T. These two patients showed
      greatly diminished HRV postoperatively with a similarly reduced circadian rhythm.
      We have demonstrated that the circadian rhythm of HRV is not preserved after
      aortic surgery. Diminished diurnal variability seems to be a general
      manifestation and myocardial ischemia may just be one contributing factor. An
      altered biorhythm in combination with stress related changes in the
      neuroendocrine system after surgery most likely have a more significant influence
      on the circadian rhythm of HRV.

PMID- 14587649
TI  - Shifting of puncture site in the fossa ovalis during radiofrequency catheter
      ablation: intracardiac echocardiography-guided transseptal left heart
      catheterization.
AB  - Intracardiac echocardiography (ICE) serves as an adjunct to fluoroscopy for
      electrophysiological procedures by identifying critical anatomic landmarks and
      confirming catheter-endocardial contact. In the present study, we investigated
      the usefulness of ICE for radiofrequency catheter ablation. ICE was utilized to
      guide transseptal puncture in 19 patients undergoing radiofrequency catheter
      ablation. The fossa ovalis, which was one critical anatomic landmark, had an
      average vertical diameter of 18.5 +/- 6.9 mm and an average horizontal diameter
      of 10.0 +/- 2.4 mm, as measured by ICE and fluoroscopy. Although there was only a
      small shift of the puncture site in the horizontal direction, the puncture site
      shifted towards the upper edge of the fossa ovalis for 17 patients (89%).
      Furthermore, we could verify that the distance between the apex of the tent-shape
      formed by the pressure of the puncture needle in the fossa ovalis and the left
      atrial wall opposing it was sufficient to carry out the procedure safely.
      Confirming the puncture site using ICE is useful in carrying out transseptal left
      heart catheterization safely.

PMID- 14587650
TI  - Effects of spironolactone and metoprolol on QT dispersion in heart failure.
AB  - The effects of spironolactone or metoprolol added to a conventional treatment
      protocol on QT dispersion, which is accepted as a sudden cardiac death predictor,
      were evaluated in heart failure patients.? A total of 105 New York Heart
      Association class III patients were included in this study. The conventional
      treatment protocol was standardized by giving ramipril, furosemide, and digoxin
      to all patients for 3 weeks at the same doses. At the end of this period, the
      patients were divided into three groups. Conventional treatment was continued in
      group 1, 25 mg spironolactone was added in group 2, and 12.5 mg metoprolol was
      added in group 3. Patients were followed for 12 weeks and clinical and laboratory
      tests were conducted at 3 week intervals. No significant change in corrected QT
      dispersion was observed in group 1 at the end of 12 weeks (corrected QT
      dispersion: 80 +/- 2 msc to 79 +/- 2 msc, P: 0.22). However, corrected QT
      dispersion in group 2 was reduced by 32.5% (83 +/- 2 msc to 56 +/- 1 msc; P:
      0.01). A 32.9% reduction in corrected QT dispersion (79 +/- 2 msc to 53 +/- 2
      msc; P: 0.01) was observed in group 3. In conclusion, the addition of
      spironolactone or metoprolol to a conventional treatment in heart failure
      patients resulted in improved clinical conditions and the significant decrease in
      sudden death predictors corrected QT dispersion. The effects of spironolactone
      and metoprolol on corrected QT dispersion were similar.

PMID- 14587651
TI  - Short-term effects of rilmenidine on left ventricular hypertrophy and systolic
      and diastolic function in patients with essential hypertension: comparison with
      an angiotensin converting enzyme inhibitor and a calcium antagonist.
AB  - The short-term (three months) effects of rilmenidine on systemic hypertension
      induced left ventricular hypertrophy (LVH) and left ventricular systolic and
      diastolic functions in comparison with those of perindopril and nifedipine-slow
      release (SR) formulation were studied. The short-term effects of rilmenidine on
      biochemical parameters and lipid profiles were evaluated. Sixty patients (39 men,
      21 women) with a mean age of 59 +/- 14 years and with mild to moderate systemic
      arterial hypertension were enrolled in three groups. The first group received 1
      mg/day of rilmenidine, the second group 4 mg/day of perindopril, and the third
      group 20 mg/day of nifedipine SR. All drugs induced a similar decrease in
      systolic and diastolic blood pressure (BP) values. Left ventricular mass (LVM)
      and LVM index decreased equally in all groups associated with a significant
      increase in the E/A ratio. The ratio between the reduction in LVM and decrease in
      mean arterial pressure (LVM/mmHg) was higher in groups 1 and 2. Negative
      correlations between LVM and LVMI. E/A, and the dv/dt ratio were obtained.
      Rilmenidine did not change the blood chemistry and lipid profile values. Despite
      its neutral effect on lipid profile and biochemical parameters. rilmenidine is as
      effective as perindopril and nifedipine in controlling hypertension and
      decreasing left ventricular hypertrophy.

PMID- 14587652
TI  - Femoral signal intensity: a new method for prediction of embolic risk.
AB  - Mitral stenotic patients with left atrial spontaneous echo contrast (LA SEC) are
      associated with high risk of thromboembolism. The aim of this study was to
      predict thromboembolic risk in mitral stenotic patients. Femoral artery signal
      intensity alteration (%) was compared among the groups. Group 1 had severe mitral
      stenosis with LA SEC and group 2 slight mitral stenosis without LA SEC. Group 3
      patients had normal transthoracic echocardiography. Femoral artery longitudinal
      view was studied with a linear USG probe (7.5 MHz, HP 2500). The femoral cuff was
      inflated to 300 mmHg, 7-12 cm below the inguinal ligament. Cuff inflation
      resulted in femoral arterial blood stasis. Intraluminal signal intensity
      increased in seconds. The femoral signal intensity alteration (%) at 180 seconds
      was compared to baseline. After femoral cuff inflation, femoral signal intensity
      alteration (%) was significantly higher in group 1 than groups 2 and 3 (P <
      0.001). Group 1 patients had higher thromboembolic risk on the basis of their
      echocardiographic, clinical, and laboratory parameters. Increased signal
      intensity alteration (%) can be detected in the femoral artery in mitral stenotic
      patients with LA SEC.

PMID- 14587653
TI  - Cyclic GMP production by ANP, BNP, and NO during worsening and improvement of
      chronic heart failure.
AB  - Cyclic GMP (cGMP) serves as an intracellular second messenger of atrial
      natriuretic peptide (ANP), brain natriuretic peptide (BNP), and nitric oxide (NO)
      and its peripheral blood concentration is an index of its biological activity. It
      has been reported that the plasma concentration of cGMP is correlated with the
      concentrations of ANP and BNP and is related to the prognosis of chronic heart
      failure patients, but the relation with NO has not been studied. Therefore, we
      investigated the roles of ANP, BNP, and NO in relation to cGMP in the blood
      during worsening and improvement of chronic heart failure. The subjects were 25
      patients who were hospitalized in our hospital for acute worsening of chronic
      heart failure. Plasma concentrations of NO, norepinephrine (NE), ANP, BNP, and
      cGMP were measured on acute worsening (admission) and improvement (discharge) of
      heart failure. The cGMP concentration on worsening showed a positive correlation
      with the NO concentration (r = (0.57, P < 0.01), but no correlations with ANP or
      BNP were observed. The cGMP concentration on improvement showed no correlation
      with the NO concentration, but a positive correlation with ANP (r = 0.69, P <
      0.001) and BNP (r = 0.67, P < 0.001). No correlation was observed between the NO
      and NE concentrations. We also studied serious cases of NYHA IV and mild cases of
      NYHA II to III. The cGMP concentration in the serious group showed a positive
      correlation with the NO concentration but no correlations with ANP or BNP
      concentrations on worsening. However, in the mild group, the cGMP concentration
      during worsening showed positive correlations with both the NO and BNP
      concentrations. On improvement, the cGMP concentration showed no correlation with
      the NO concentration but positive correlations with both the ANP and BNP
      concentrations in both the severe and mild groups. The results suggest the
      possibility that cGMP is produced mainly by NO during worsening, and by ANP and
      BNP rather than NO during improvement of chronic heart failure.

PMID- 14587654
TI  - Neurohormonal determinants of peak oxygen uptake in patients with chronic heart
      failure.
AB  - Chronic heart failure (CHF) is characterized by the activation of neurohormones
      and cytokines. This study determined whether peak oxygen uptake (VO2) can be
      predicted by the degree of neurohormonal and cytokine activations in CHF. Plasma
      norepinephrine. epinephrine, renin-angiotensin system activity, ANP, BNP, and
      serum interleukin-6 (IL-6) and tumor necrosis factor (TNF)-alpha were measured in
      84 CHF patients (age, 59 +/- 1 years, LVEF, 36 +/- 1%) and 34 controls. Maximal
      cardiopulmonary exercise testing was performed. Peak VO2 (Controls vs CHF: 27.8
      +/- 1.3 vs 18.2 +/- 0.5 mL/min/kg, P < 0.0001) was lower in CHF. Patients with
      CHF had increased plasma norepinephrine (211 +/- 11 vs 315 +/- 24 pg/mL), renin
      activity (1.2 +/- 0.2 vs 6.2 +/- 1.1 ng/mL/hr), ANP (22 +/- 3 vs 72 +/- 7 pg/mL),
      and BNP levels (18 +/- 3 vs 200 +/- 25 pg/mL) (all P < 0.01). Serum IL-6 (1.1 0.1
      vs 2.4 +/- 0.3 pg/mL) and TNF-alpha (2.7 +/- 0.2 vs 4.0 +/- 0.3 pg/mL) levels
      were higher in CHF (both P < 0.001). Univariate analysis revealed that age (P <
      0.001), cardiothoracic ratio (P < 0.001), norepinephrine (P < 0.0001), ANP (P <
      0.001), BNP (P < 0.01), and log IL-6 (P < 0.05) were significantly related with
      peak VO2. Stepwise regression analysis indicated that plasma norepinephrine and
      ANP emerged as significant determinants of peak VO2, independent of patient age
      (overall R = 0.61, P < 0.0001). In summary, patients with CHF exhibited
      activation of neurohormones and proinflammatory cytokines. Among the elevated
      hormonal and cytokine markers, plasma norepinephrine and ANP levels were
      independent predictors of exercise capacity.

PMID- 14587655
TI  - Effects of imidapril and TA-606 on rat dilated cardiomyopathy after myocarditis.
AB  - For the management of chronic heart failure, both angiotensin converting enzyme
      inhibitors (ACEI) and angiotensin II type 1 receptor blockers (ARB) are useful,
      however, the differences between the two groups of agents are unclear. We
      compared the effects of long-term treatment with an ACEI (imidapril) and an ARB
      (TA-606) in rats that had recovered from experimental autoimmune myocarditis
      (EAM). Forty-two Lewis rats were immunized with porcine cardiac myosin on day 0
      and divided into 6 groups, group C (distilled water), group IL (imidapril 0.5
      mg/kg/day), group IH (imidapril 2 mg/kg/day), group TL (TA-606 2 mg/kg/day),
      group TH (TA-606 6 mg/kg/day), and group IT (imidapril 0.5 mg/kg/day + TA-606 2
      mg/kg/day). Drugs were administered from day 28. Hemodynamic parameters, heart
      weight/body weight ratio (HW/BW), and area of fibrosis were measured on days 70
      74. Only the high dose of imidapril significantly decreased central venous
      pressure and significantly increased maximum dP/dt and the absolute value of
      minimum dP/dt. HW/BW was suppressed in groups IH, TH, and IT. Thus, in treatment
      of chronic heart failure in rats, a sufficient dose of ACEI was needed to improve
      hemodynamics and to prevent ventricular hypertrophy. The hemodynamic effects of
      ARB and combination therapy of both drugs at low doses were not significant.

PMID- 14587656
TI  - Vanadate improves cardiac function and myocardial energy metabolism in diabetic
      rat hearts.
AB  - Vanadium mimicking the metabolic effects of insulin is known to decrease serum
      glucose levels and to influence glucose metabolism in diabetes mellitus. However,
      it is unclear whether vanadium ameliorates the metabolic disorder in diabetic
      hearts causing myocardial dysfunction. The purpose of this study was to assess
      the effects of vanadium on cardiac performance and energy metabolism in diabetic
      rat hearts. Four groups of Wistar rats were studied: untreated control rats
      (group C, n = 8). vanadate-treated rats (group V, n = 10), untreated diabetic
      rats (group DM, n = 9) induced by streptozotocin. and vanadate-treated diabetic
      rats (group DMV, n = 8). Vanadate-treated rats drank a 1.5 mM sodium
      orthovanadate (Na3VO4) solution during a 4 week diabetic condition. Hearts were
      perfused with Krebs-Henseleit buffer after the diabetic duration. After the
      maximum left ventricular dP/dt and cardiac efficiency were calculated, the
      myocardial contents of ATP and creatine phosphate (P-Cr) and myocardial energy
      metabolism were assessed by cytosolic phosphorylation potential. Peak positive
      and negative dP/dt, and cardiac efficiency decreased significantly in group DM
      compared with group C, while there were no significant differences between groups
      C and DMV. The myocardial contents of ATP (micromol/g wet heart) and P-Cr
      (micromol/g wet heart), and cytosolic phosphorylation potential (M(-1)) increased
      from 2.72 +/- 0.46. 1.45 +/- 0.58. and 3,530 +/- 1,220 in group DM to 3.88 +/-
      0.76, 3.81 +/- 1.36, and 11,200 +/- 2,400 in group DMV, respectively. It is
      concluded that vanadium restored the production of high energy phosphates in the
      myocardium and improved myocardial dysfunction by regulating metabolic processes
      in diabetic rat hearts.

PMID- 14587657
TI  - Primary coronary angioplasty with stenting for acute coronary syndrome in
      patients with isolated single coronary artery: a report of 2 cases.
AB  - We report 2 cases with an isolated single coronary artery who underwent
      successful primary coronary intervention for acute coronary syndrome. Although
      coronary angioplasty with stenting may be a feasible therapeutic option for
      atherosclerotic stenosis in a single coronary artery, the operator should be
      aware of the potential risk of complications.

PMID- 14587658
TI  - Cholesterol crystal embolization (CCE) after cardiac catheterization: a case
      report and a review of 36 cases in the Japanese literature.
AB  - Cholesterol crystal embolization (CCE) is a complication of atherosclerosis. A 67
      year-old Japanese man underwent coronary artery bypass grafting. After the
      surgery, he underwent coronary angiography via the right femoral artery. Twelve
      days later, he suddenly developed acalculous cholecystitis and was treated with
      antibiotics. Gradual deterioration in renal function, purplish discoloration of
      the distal portion of his toes, and eosinophilia were noted. We performed a skin
      biopsy and made a diagnosis of CCE. Cilostazol and intravenous heparin improved
      the symptoms and decreased the creatinine level. We retrospectively studied the
      clinical features of 36 cases registered with a diagnosis of CCE in the Japanese
      literature.

PMID- 14587659
TI  - Coexistence of familial hypertrophic cardiomyopathy and vasospastic angina
      pectoris in two brothers.
AB  - Two brothers had familial hypertrophic cardiomyopathy and vasospastic angina
      pectoris concurrently. Their family history showed that one of their sisters had
      hypertrophic cardiomyopathy and another brother died suddenly at age 52. The
      clinical diagnosis of hypertrophic cardiomyopathy was confirmed by an
      echocardiogram and left ventriculography. They had typical chest pain at rest,
      and a significant vasospasm of coronary arteries with chest pain and obvious ST-T
      changes in the electrocardiograms was provoked by intracoronary injection of
      acetylcholine in both patients. The administration of a calcium antagonist and
      nitrate was effective for ameliorating chest pain with no cardiovascular events
      during the follow up period of more than 3 years. Although underlying
      pathophysiologic abnormalities of familial hypertrophic cardiomyopathy and
      vasospastic angina pectoris are considered to be transmitted genetically, the
      genetic backgrounds of these cases remain to be clarified.

PMID- 14587660
TI  - A case of sick sinus syndrome that developed torsades de pointes, pacing failure
      and sensing failure during administration of bepridil.
AB  - A 65-year-old Japanese woman was admitted to hospital because of palpitations and
      faintness. She was diagnosed as having sick sinus syndrome and a permanent
      pacemaker was therefore implanted. Administration of bepridil (200 mg daily) was
      started for prevention of atrial flutter and fibrillation after PM implantation.
      On the twenty-fifth day of Bpd therapy, she developed recurrent syncope, ECG
      showed QT prolongation. torsades de pointes, and sensing failure. Electrical
      defibrillation (DF) was performed for ventricular fibrillation or ventricular
      tachycardia. It was presumed that Bpd had caused not only proarrhythmia but also
      a transient decrease in the amplitude of ventricular activation at the site of
      the pacing lead, as the sensing level was gradually restored after the drug was
      ceased and her plasma concentrations of Bpd decreased. It is also believed that
      DF had caused a sustained increase in pacing threshold because she developed
      pacing failure after DF and her pacing threshold had not returned to its prior
      level although the blood levels of Bpd had been below the minimum detectable
      level. Although it is well known that torsades de pointes occasionally develops
      in association with Bpd therapy, it is less evident that pacing and sensing
      failure may develop in association with Bpd therapy. This case report suggests
      that we should be aware of this possible outcome when employing Bpd and pacemaker
      implantation as combination therapy.

PMID- 14587661
TI  - Atrioventricular block during atrioventricular nodal reentrant tachycardia is not
      always benign.
AB  - A 70-year-old Japanese woman was admitted to our hospital because of transient
      second degree atrioventricular (AV) block. An electrophysiologic study (EPS) was
      performed, and Mobitz type II infra-Hisian block during atrial pacing at a rate
      of 130/min was noted. An AV nodal reentrant tachycardia (AVNRT) was induced by
      ventricular pacing at a rate of 180/min, and 2:1-3:1 infra-Hisian block during
      AVNRT was observed. The AV block and AVNRT rarely occurred in the clinical
      setting, and the patient did not complain of any symptoms related to these
      arrhythmias. Therefore, the patient refused permanent pacemaker implantation,
      although she continued to be followed in our outpatient clinic. However, the
      patient was re-admitted one year later because of palpitations and dyspnea upon
      exertion related to the AV block. The 12-lead ECG showed high degree AV block
      with narrow QRS complexes. The patient underwent pacemaker implantation during
      the subsequent hospitalization, and her symptoms improved postoperation. AV block
      during AVNRT is sometimes observed, and it has been considered as a functional AV
      block. In the present case, a pathologic conduction disturbance in the His
      Purkinje system caused the high degree AV block during AVNRT. The high degree AV
      block during AVNRT may indicate the existence of a conduction disturbance in the
      His-Purkinje system in some of these types of cases.

PMID- 14587662
TI  - Papillary fibroelastoma of the aortic valve: evaluation with transesophageal
      echocardiography and magnetic resonance imaging.
AB  - A 74-year-old Japanese male was admitted to hospital with episodes of chest pain.
      Cross-sectional echocardiography showed a mobile mass adherent to the noncoronary
      cusp of the aortic valve. We employed transesophageal echocardiography and
      magnetic resonance imaging to evaluate the mass. Based on the findings, a
      papillary fibroelastoma of the aortic valve was suspected. To avoid systemic
      embolization, urgent surgery was performed. The histopathologic diagnosis was
      papillary fibroelastoma. When a tumor of the aortic valve exists, these
      examinations are useful in detecting and characterizing the tumor for optimal
      treatment.

PMID- 14587663
TI  - High output heart failure 8 months after an acquired arteriovenous fistula.
AB  - Congestive heart failure (CHF) due to hyperkinetic states can occur in systemic
      diseases and in arteriovenous fistulas. An 18 year old Turkish male patient
      complaining of dyspnea and palpitations, who had suffered a stab wound to his
      abdomen eight months earlier, was admitted to our clinic. Auscultation revealed a
      systolodiastolic murmur over the entire abdomen. Chest x-rays demonstrated
      significant cardiomegaly. Echocardiography revealed biatrial enlargement and
      significant mitral and tricuspid regurgitation accompanied by dilatation of the
      inferior vena cava. Right heart catheterization showed increased oxygen
      saturation at the inferior vena cava. A diagnosis of an aortocaval fistula was
      made by aortography. The symptoms subsided and valvular regurgitations ceased
      alter surgical correction. This rare case demonstrates the significance of
      routine physical examination and history of the patient.

PMID- 14587664
TI  - Characterization of four novel variants of goat beta(A) -globin gene.
AB  - Four novel alleles of the adult beta-globin gene of Capra hircus were observed in
      an extended study on hemoglobin polymorphism in goat breeds living in the island
      of Sardinia Nucleotide sequencing showed that one of these alleles is due to a 2
      bp substitution at codon 125 (CTG --> GAG, Leu --> Glu). Two substitutions, the
      silent CTT --> CTC for Leu at codon 78 and the conservative AAG --> AGG (Lys -->
      Arg) at codon 104, are shared by the other three alleles, two of them having
      additional mutations, which suggests a common origin. The allele we provisionally
      called the beta(Y) shares four out of five amino acid substitutions, together
      with the same polymorphisms in the IVSII, we observed previously in the rather
      common beta(E) gene. This evidence allowed the origin of the beta(E) gene to be
      better characterized. The data increase to seven the number of alleles at the
      goat beta(A)-globin locus characterized thus far at the molecular level. A
      simplified nomenclaturefor the increasing number of goat beta-globin alleles is
      presented.

PMID- 14587665
TI  - Temporal and spatial allozyme variation in the South American cactophilic
      Drosophila antonietae (Diptera; Drosophilidae).
AB  - Drosophila antonietae is an endemic South American cactophilic species that uses
      Cereus hildmaniannus rotting cladodes as breeding sites. We assessed temporal and
      spatial intrapopulational allozyme variation of two natural populations. Our
      results suggest that environmental variation (rain precipitation) is probably
      influencing allozyme temporal variation. Moreover, it seems that D. antonietae
      does not have intrapopulation structure and has N(ev) (variance effective size)
      approximately equal to 83 and N(ec) (number of adult flies that colonize each
      rotting cladode) = 21. The deficiency of heterozygotes found must be due to null
      alleles, a temporal Wahlund effect, or selection against heterozygotes.
      Assortative mating and inbreeding are discarded. This is the first report on
      allozyme variation in D. antonietae. It gives some insight on intrapopulational
      genetics through space and time for this species. This is important to understand
      its general genetic variability and will be essential to future works on the
      natural history and evolution of this species.

PMID- 14587666
TI  - A high mobility group protein from the Dipteran insects Ceratitis capitata and
      Bactrocera oleae.
AB  - Nuclei from Bactrocera oleae and Ceratitis capitata larvae contain a major
      protein that shares most of the characteristics of vertebrate high mobility group
      (HMG) proteins. Proteins are extracted from nuclei with 0.35 M NaCl, are soluble
      in 5% perchloric acid, are relatively small (molecular weight in the range of 10
      16 kDa), and have both a high basic and a high acidic amino acid content. The
      amino acid constitution of these proteins is similar to that of the HMGB protein
      family of vertebrates. The proteins cross-react with antibodies raised against
      the HMGD chromosomal protein of Drosophila melanogaster. The possible relatedness
      of these proteins to high mobility group proteins is discussed.

PMID- 14587667
TI  - Cloning and identification of a novel cDNA which encodes a putative protein with
      a DnaJ domain and a thioredoxin active motif, human macrothioredoxin.
AB  - A 3345 bp cDNA was isolated from the fetal brain cDNA library by high throughput
      cDNA sequencing. The cDNA with an open reading fragment (ORF) of 2241 bp encodes
      a 747 amino acids putative protein with a DnaJ N-terminus domain and four
      thioredoxin active sets. So it is named human macrothioredoxin (hMTHr). We used
      Northern blot to detect a band with a length of about 5 kb, which was
      ubiquitously expressed in human adult tissues with different intensities. The
      expression pattern was verified by RT-PCR, revealing that the transcripts were
      ubiquitously expressed in fetal tissues and human tumor tissues also. The
      transcripts in fetal tissues were more numerous than in adult tissues. The
      transcripts were high in adult testis, adult pancreas, fetal thymus, and fetal
      kidney. We have found three splice isoforms with lengths of 3483, 3345, and 2982
      bp in the sequencing analysis of the RT-PCR products. They encode three putative
      proteins with 793, 747, and 275 amino acids, respectively. The first two putative
      proteins contain a DnaJ domain and four thioredoxin domains. The third putative
      protein only contains an N-terminus DnaJ domain and one thioredoxin active set.
      Blast analysis against the NCBI database revealed that the gene spans a genome
      sequence of about 75 kb that contains at least 25 exons and is located in human
      chromosome 2q32.1. The organization of the functional motifs of hMTHr suggests
      that the protein might be a member of a molecular chaperone family.

PMID- 14587668
TI  - Expression of two isoform mRNAs of nucleolar protein B23 during rat liver
      regeneration.
AB  - Nucleolar protein B23 exists in two isoforms designated as B23.1 and B23.2,
      differing only in their carboxy-terminal short sequences. To clarify the levels
      of protein B23 isoform mRNAs in the cell cycle, we have investigated the
      expressions of the two mRNAs during rat liver regeneration. Both of B23 isoforms
      transcripts increased after a partial hepatectomy. Peaks of the mRNAs were
      observed after 9 h (fivefold) with B23.1 and 12 h (twofold) with B23.2,
      respectively. These two peaks were slightly preceding the onset of DNA synthesis,
      which was revealed by the activity of DNA polymerase alpha. From these
      observations, important roles of both protein B23 isoforms in stimulation of DNA
      polymerase a activity during rat liver regeneration were suggested.

PMID- 14587669
TI  - Isoform-dependent phenol oxidase activity during the developmental stages in
      Drosophila melanogaster.

PMID- 14587670
TI  - The failure of dentistry's social contract with America and California's search
      for legislative solutions?

PMID- 14587671
TI  - Dental technology training in Israel.

PMID- 14587672
TI  - Professional monopoly, social covenant, and access to oral health care in the
      United States.
AB  - Lack of access to oral care is a severe problem in the United States with over
      one-third of the population lacking dental insurance. In this group, 32 million
      people lack dental insurance and access to public dental services (Medicaid or
      Medicare), and 7 million of them need dental care. In some high-risk populations,
      such as Native Americans, two-thirds have unmet dental needs. Only 1 percent of
      Medicaid-eligible babies have a dental examination before twelve months of age.
      In this paper the social covenant of the dental profession is examined and
      suggestions made for improving access to care through improved efficiency. It is
      proposed that 1) private dentists should accept 5 percent per annum of their
      patients for indigent care funded by improved efficiency from utilizing allied
      dental providers (ADP) in new roles, and 2) ADP should have their own independent
      state boards. If dentists refuse to honor their social covenant, then ADP should
      be allowed to practice independently, breaking the professional monopoly.

PMID- 14587673
TI  - Salivary biomarkers associated with academic assessment stress among dental
      undergraduates.
AB  - This study aims to assess the difference in self-perceived stress before and
      after an academic assessment and its association with the marks scored and to
      study the association of salivary cortisol, Immunoglobulin A (IgA), and
      chromogranin A (CgA) with stress levels before and after the assessment. Thirty
      one third-year dental undergraduates indicated how stressed they felt on a 5
      point rating scale just prior to and immediately after a one-hour written test.
      Five-minute unstimulated whole saliva samples were also collected at those times
      to measure salivary cortisol, IgA, and CgA. Students rated significantly higher
      stress scores before (median [inter quartile range]: 3[1]), compared to after the
      test (2[2]) (p = 0.015). Higher cortisol levels (mean: 6.32 nmol/l) were observed
      before than after the exam (mean: 5.16 nmol/l) (p = 0.015). No significant
      differences were noted between the pre- and post-test saliva samples for salivary
      IgA and CgA levels. A negative correlation was seen between post-test stress
      scores and test marks (Spearman's r = -0.325, p = 0.07). Dental students
      perceived a higher level of stress prior to the test, which declined after that.
      Pre-test stress scores were associated with raised salivary cortisol, but not IgA
      or CgA. Students who perceived higher levels of stress after the test generally
      had poorer results.

PMID- 14587675
TI  - Effective recruitment and retention strategies for underrepresented minority
      students: perspectives from dental students.
AB  - This study was designed to identify reasons underrepresented minority (URM)
      dental students select a dental school and to determine the factors that
      contribute to their resolve to complete their programs. A survey questionnaire
      developed from interviews with URM students was sent to Minority/Admissions
      Officers or deans of dental schools that enrolled URM students for distribution
      to their minority students. A total of 198 questionnaires were received from
      minority students in all levels of dental school. The results were that 74
      percent said they selected a school for its reputation, and 49.5 percent chose a
      dental school even if the financial aid package was less than what was offered in
      other schools. African American, Hispanic, and Native American students prefer
      integrated interview days with nonminority applicants and disapprove of "special"
      days designated for URMs. The presence of other minority students was not an
      important factor in the selection of a school but is an important source of
      support while attending dental school. Dental school minority alumni also play a
      significant role in the selection of a school. Results of the study can be useful
      in planning recruitment and retention programs.

PMID- 14587674
TI  - A survey of information technology management at U.S. dental schools.
AB  - The purpose of this project is to assess how information technology (IT) is being
      implemented and managed in U.S. dental schools. Recent advances in IT have
      restructured many of the administrative, curricular, and clinical functions in
      dental schools. Purchasing hardware and software and hiring personnel to maintain
      IT present significant financial and administrative commitments for these
      schools. A nine-question survey was sent to all U.S. dental schools via email
      with a follow-up postal mailing. Forty-six surveys were returned (83.6 percent
      response rate). The analysis indicates that dental schools are managing IT in
      vastly different ways. For example, 71 percent of the schools report a
      centralized structure, and 61 percent have a line item in the budget to manage
      IT. On average there are 4.4 full-time equivalents hired to manage IT, with the
      majority of these people being trained in IT (eight schools reported dually
      trained IT/dental personnel). The majority of schools report using software to
      manage their admissions process (70 percent), curriculum analysis (72 percent),
      and delivery of curriculum content (72 percent), as well as to manage their
      student clinics (91 percent, business aspect; 87 percent, patients; 65 percent,
      grading on clinic floor; 76 percent, managing clinical evaluations) and faculty
      practices (85 percent, business aspect; 65 percent, patients). The use of
      multimedia (50 percent) and simulation (52 percent) in the preclinical area is
      mixed. The purchase of laptops (24 percent) and PCs (11 percent) is required in
      almost a third of all schools participating in this survey. Dental schools in the
      United States are managing IT in a variety of different ways, using various
      internally and commercially available tools. The cost to institutions can be
      large and is usually handled in centralized structures in the school with fixed
      budgets. The results of this survey can be used to assist schools in the planning
      and implementation of IT at their institutions.

PMID- 14587676
TI  - A model for assessing the ethical environment in academic dentistry.
AB  - Weber's "Institutional Ethics Audit" model was designed as a tool for assessment
      of an organization's effort to institutionalize ethics into its operations. In
      this model, the overall ethical environment of an organization is evaluated
      through an assessment of its 1) ethical cultures, 2) ethics policy, 3)
      enforcement mechanisms, and 4) ethical training. Assessment of these components
      allows the organization to be placed along a continuum that spans aethical firms,
      compliance firms, emerging firms, and integrity firms. This paper presents the
      conceptual framework for this model. We propose that application of this model to
      academic institutions, including dental schools, could provide appropriate
      information to improve the ethical climate of the institution.

PMID- 14587677
TI  - Enhancing academic integrity: formulating effective honor codes.
AB  - Academic integrity continues to be of concern in higher education as the data
      from undergraduate schools shows an increasing prevalence of cheating behaviors
      and changing values of students who are entering dental education. The use of
      honor codes has been reported to positively influence the attitudes and behaviors
      of students. This paper discusses the elements of an effective and valid honor
      code and its possible role in enhancing the dental school environment.

PMID- 14587678
TI  - Caries vaccines for the twenty-first century.
AB  - Can infection with the dental caries pathogen, Streptococcus mutans, be
      intercepted or modified immunologically? Resolving this question requires answers
      to many questions: What are the pathways by which this cariogenic streptococcus
      enters and accumulates in the dental biofilm? Can bacterial components associated
      with virulence induce immune responses? What is the level of maturity of immune
      pathways in the oral cavity of the young child at the time of infection? Can
      immune strategies deal effectively with chronic S. mutans infections? Are these
      vaccines safe? Many such questions have been answered. For example, preclinical
      application of modern methods of mucosal vaccine design and delivery has
      routinely resulted in protection from dental caries caused by S. mutans
      infection, using antigens involved in the sucrose-independent or sucrose
      dependent mechanisms of infection by these cariogenic streptococci. Passive
      administration of antibody to functional epitopes of S. mutans virulence antigens
      has also provided a degree of protection in preclinical studies and small-scale
      human investigations. The caries-protective capacity of active immunization with
      dental caries vaccines now awaits proof of principle in pediatric clinical
      trials.

PMID- 14587679
TI  - Factors affecting stress among Indian dental students.
AB  - The aim of this study was to investigate the perceived sources of stress and the
      role of parents in its etiology among dental students in a private dental school
      in India. A modified Dental Environment Stress (DES) Questionnaire was
      administered to 256 dental students. The main sources of stress were found to be
      fear of facing parents after failure, full loaded day, and fear of failing course
      or year. Students whose first choice of admission was dentistry experienced less
      stress than students whose first choice was another field. Also the students who
      joined dentistry due to parental pressure showed greater stress than those who
      joined of their own accord. Male students experienced greater stress than
      females. The results of this study indicate that a congenial environment needs to
      be created for dental education and parents also need to be counseled against
      forcing their children to join an educational program that is not of their
      choice.

PMID- 14587680
TI  - A survey of deans and ADEA activities on dental licensure issues.
AB  - A written survey on issues in clinical testing for licensure was sent to the
      deans of all dental schools in the United States. Response rate was 89 percent.
      Results indicate that administrative leaders of the country's dental schools
      think that third-party evaluation of graduates is appropriate, but they do not
      have confidence in current clinical tests for licensure. More than nine out of
      ten respondents indicated that change was needed in current testing procedures,
      and 82 percent thought the tests as currently conducted were not valid for
      decision purposes. Regional differences existed among the responses, with the
      least dissatisfaction occurring in the West. The highest-rated and most
      frequently mentioned reasons for dissatisfaction with clinical tests were the
      involvement of patients (human subjects) as currently done. Most respondents
      favored a national level for licensure tests, although the majority also approved
      of the recently enacted New York law that permits completion of a postgraduate
      year in an accredited program to substitute for clinical testing. Respondents
      indicated a belief that a national database on academic measures as compared to
      outcomes on clinical licensure tests would be useful, with overall grade point
      average or class rank as the favored academic measure. Informed by the
      recommendations of its representatives to the AADE-ADEA Innovative Testing and
      Educational Methodologies Committee and results of the survey of deans, ADEA is
      pursuing steps to foster change in the clinical licensure process.

PMID- 14587681
TI  - Arnica and induction.

PMID- 14587682
TI  - Effects of homeopathic treatment on pruritus of haemodialysis patients: a
      randomised placebo-controlled double-blind trial.
AB  - Pruritus is a frequent and difficult to treat problem in haemodialysis. This
      double-blind placebo-controlled randomised clinical trial assessed the role of
      homeopathic treatment in this situation. The code was held by the pharmacist who
      dispensed the medications. Pruritus was evaluated using a previously published
      scale. Only patients with initial values above 25% of maximum pruritus score were
      entered. Data were analysed after partial code break, separating the two groups
      of patients, but with no awareness of which one received verum or placebo.
      Patients were classified as responders if they had >50% reduction of pruritus
      score. Twenty-eight patients (16M/12F, 51 +/- 11 years of age) were entered and
      20 (12M/8F, 52 +/- 8 years of age) remained for final analysis: 11 in the verum
      group, 9 in placebo. At entry, the mean pruritus score was 65 +/- 25% for the
      treated patients and 70 +/- 27% for placebo. After 15, 30, 45, and 60 days of
      follow-up, pruritus score were respectively: 46 +/- 29, 41 +/- 30, 42 +/- 29, and
      38 +/- 33 for the treated patients and 61 +/- 29, 67 +/- 31, 64 +/- 35, and 57 +/
      39 for placebo. Reduction was statistically significant (P<0.05) at every point
      of observation. According to the patients' own assessment, at the end of the
      study period, the homeopathic treatment reduced the pruritus score by
      approximately 49%. Responders were more frequent in the treated group with
      statistical significance at 30 days (0% vs 45%, P=0.038). Homeopathic treatment
      may represent a worthwhile alternative to relieve pruritus in patients undergoing
      haemodialysis.

PMID- 14587683
TI  - Assessing likelihood ratio of clinical symptoms: handling vagueness.
AB  - Clinical symptoms including homeopathic symptoms are often vague. There is
      reluctance to assess clinical symptoms as diagnostic instruments because they are
      hard to define. Still, clinical symptoms appear effective in daily practice.
      Expert systems and neural networks handle vague data successfully. Theoretical
      considerations predict the kind of problems we may expect. There is a difference
      between quantitative and qualitative vagueness. Vague data cause problems if we
      try to prove a hypothesis because of expectation bias. We assess likelihood ratio
      of homeopathic symptoms only to improve the method.

PMID- 14587685
TI  - Exploring General Practitioners' attitudes to homeopathy in Dumfries and
      Galloway.
AB  - This comparative quantitative study explored General Practitioners' (GPs)
      attitudes to homeopathy in Dumfries and Galloway, a predominantly rural area in
      South West Scotland where there is a local British Homeopathic Association Funded
      Homeopathic Clinic. It aimed to determine whether there was an association
      between expressed attitudes to homeopathy and a number of variables. Issues
      arising from the House of Lords Report on CAM were also explored. A self
      administered questionnaire was addressed to all 135 GPs within Dumfries and
      Galloway. Descriptive statistics were used in the data analysis. The response
      rate was 75%. The NHS GP clinic accounted for 47% of total referrals for
      homeopathy. A total of 86.1% of GPs within Dumfries and Galloway were in favour
      of a local NHS Homeopathic Specialist Clinic. Forms of evidence most influential
      to GPs regarding homeopathy were: randomised controlled trials; audit data on
      patient outcomes; safety and patient satisfaction.

PMID- 14587684
TI  - Effect of Arnica D30 in marathon runners. Pooled results from two double-blind
      placebo controlled studies.
AB  - OBJECTIVE: To examine whether the homeopathic medicine Arnica D30 has an effect
      on muscle soreness and cell damage after marathon running. METHODS: The subjects
      were 82 marathon runners from two separate randomised double-blind placebo
      controlled trials participating in the Oslo Marathon in 1990 and 1995. Five pills
      of Arnica D30 or placebo were given morning and evening. Treatment started on the
      evening before the marathon and continued on day of the race and the three
      following days. The runners assessed muscular soreness on a visual analogue
      scale. Muscle enzymes, electrolytes and creatinine were measured before and after
      the marathon. RESULTS: Muscle soreness immediately after the marathon run was
      lower in the Arnica group than in the placebo group (P = 0.04). Cell damage
      measured by enzymes was similar in the Arnica and the placebo group. CONCLUSION:
      These pooled results suggest that Arnica D30 has a positive effect on muscle
      soreness after marathon running, but not on cell damage measured by enzymes.

PMID- 14587686
TI  - Effects of homeopathic arsenic on tobacco plant resistance to tobacco mosaic
      virus. Theoretical suggestions about system variability, based on a large
      experimental data set.
AB  - CONTEXT: This research aimed at verifying the efficacy of homeopathic treatments
      by plant-based bioassays, which may be suitable for basic research, because they
      lack placebo effects and provide large datasets for statistical analyses.
      OBJECTIVE: To evaluate the effects of homeopathic treatments of arsenic trioxide
      (As2O3) on tobacco plants subjected to tobacco mosaic virus (TMV) inoculation as
      biotic stress. DESIGN: Blind, randomized experiment using tobacco leaf disks.
      MATERIALS AND METHODS: Tobacco plants (Nicotiana tabacum L. cultivar Samsun)
      carrying the TMV resistance gene N. TMV inoculated leaf disks were floated for 3
      days in the following: Distilled water (control). H2O 5 and 45 decimal and
      centesimal potencies. As2O3 5 and 45 decimal and centesimal potencies. The main
      outcome measures is the number of hypersensitive lesions observed in a leaf disk.
      RESULTS: Homeopathic treatments of arsenic induce two effects on the plant: (i)
      increased resistance to TMV; (ii) decrease variability between experiments
      (system variability). CONCLUSIONS: In this experimental model two actions of
      homeopathic treatment were detected: decrease in system variability and
      enhancement of the natural tendency of the system towards an 'equilibrium point'.

PMID- 14587687
TI  - Complexity science and homeopathy: a synthetic overview.
AB  - Homeopathy is founded on 'holistic' and 'vitalistic' paradigms, which may be
      interpreted--at least in part--in terms of a framework provided by the theory of
      dynamic systems and of complexity. The conceptual models and some experimental
      findings from complexity science may support the paradoxical claims of similia
      principle and of dilution/dynamization effects. It is argued that better
      appreciation of three main properties of complex systems: non-linearity, self
      organization, and dynamicity, will not only add to our basic understanding of
      homeopathic phenomena but also illuminate new directions for experimental
      investigations and therapeutic settings.

PMID- 14587688
TI  - Is assessment of likelihood ratio of homeopathic symptoms possible? A pilot
      study.
AB  - A pilot study was performed to investigate the possibilities and restrictions of
      likelihood ratio (LR) investigation using three symptoms. Qualitative vagueness
      and expectation bias is inherent in our method, but is, in part avoidable. It
      appears that experienced observers assess common homeopathic symptoms quite
      similarly. Clinical judgement is an essential part of our work and should be
      preserved during assessment of LR. The assessment does not influence clinical
      practice and can be maintained for a long period, provided the appropriate
      software is used. A limited range of symptoms seems most suitable for LR
      investigation.

PMID- 14587689
TI  - The benefits of Arnica: 16 case reports.
AB  - Following the publication of a randomised controlled trial of Arnica in hand
      surgery, a number of reports of apparently beneficial effects of Arnica came to
      the author's attention. Many of these apparent responses could have been due to
      other factors including the use of herbal (non-diluted) Arnica, placebo response
      and natural course of disease.

PMID- 14587690
TI  - 20 years ago: British Homoeopathic Journal, October 1983.

PMID- 14587691
TI  - The memory of water regained?

PMID- 14587692
TI  - The challenges of clinical case reporting. Delphi Project Conference, London, 2
      April 2003.

PMID- 14587693
TI  - BBC TV Horizon programme on homeopathy.

PMID- 14587694
TI  - Principles of homeopathy.

PMID- 14587695
TI  - Article by A Jain: Does homeopathy reduce the cost of conventional drug
      prescribing?

PMID- 14587696
TI  - Interactions between tsetse and trypanosomes with implications for the control of
      trypanosomiasis.
AB  - Tsetse flies (Diptera: Glossinidae) are vectors of several species of pathogenic
      trypanosomes in tropical Africa. Human African trypanosomiasis (HAT) is a
      zoonosis caused by Trypanosoma brucei rhodesiense in East Africa and T. b.
      gambiense in West and Central Africa. About 100000 new cases are reported per
      year, with many more probably remaining undetected. Sixty million people living
      in 36 countries are at risk of infection. Recently, T. b. gambiense
      trypanosomiasis has emerged as a major public health problem in Central Africa,
      especially in the Democratic Republic of Congo, Angola and southern Sudan where
      civil war has hampered control efforts. African trypanosomes also cause nagana in
      livestock. T. vivax and T. congolense are major pathogens of cattle and other
      ruminants, while T. simiae causes high mortality in domestic pigs; T. brucei
      affects all livestock, with particularly severe effects in equines and dogs.
      Central to the control of these diseases is control of the tsetse vector, which
      should be very effective since trypanosomes rely on this single insect for
      transmission. However, the area infested by tsetse has increased in the past
      century. Recent advances in molecular technologies and their application to
      insects have revolutionized the field of vector biology, and there is hope that
      such new approaches may form the basis for future tsetse control strategies. This
      article reviews the known biology of trypanosome development in the fly in the
      context of the physiology of the digestive system and interactions of the immune
      defences and symbiotic flora.

PMID- 14587697
TI  - Enzymes involved in the biogenesis of the nematode cuticle.
AB  - Nematodes include species that are significant parasites of man, his domestic
      animals and crops, and cause chronic debilitating diseases in the developing
      world; such as lymphatic filariasis and river blindness caused by filarial
      species. Around one third of the World's population harbour parasitic nematodes;
      no vaccines exist for prevention of infection, limited effective drugs are
      available and drug resistance is an ever-increasing problem. A critical structure
      of the nematode is the protective cuticle, a collagen-rich extracellular matrix
      (ECM) that forms the exoskeleton, and is critical for viability. This resilient
      structure is synthesized sequentially five times during nematode development and
      offers protection from the environment, including the hosts' immune response. The
      detailed characterization of this complex structure; it's components, and the
      means by which they are synthesized, modified, processed and assembled will
      identify targets that may be exploited in the future control of parasitic
      nematodes. This review will focus on the nematode cuticle. This structure is
      predominantly composed of collagens, a class of proteins that are modified by a
      range of co- and post-translational modifications prior to assembly into higher
      order complexes or ECMs. The collagens and their associated enzymes have been
      comprehensively characterized in vertebrate systems and some of these studies
      will be addressed in this review. Conversely, the biosynthesis of this class of
      essential structural proteins has not been studied in such detail in the
      nematodes. As with all morphogenetic, functional and developmental studies in the
      Nematoda phylum, the free-living species Caenorhabditis elegans has proven to be
      invaluable in the characterization of the cuticle and the cuticle collagen gene
      family, and is now proving to be an excellent model in the study of cuticle
      collagen biosynthetic enzymes. This model system will be the main focus of this
      review.

PMID- 14587699
TI  - Catalytic reduction of dinitrogen under mild conditions.

PMID- 14587698
TI  - Diagnosis of human filariases (except onchocerciasis).
AB  - The traditional method of diagnosing filarial infections is to examine blood or
      skin samples for microfilariae and for many this is still the standard procedure.
      However, since the present global campaign to eliminate lymphatic filariasis new
      diagnostic tools have emerged like PCR, antigen detection using finger-prick
      blood taken during the day and ultrasound to visualize adult worms. The last two
      can be applied in endemic countries with limited resources and enable the
      detection of early infections. As well as their value in control schemes, the
      latter is particularly important for the individual since recent research has
      shown that damage is usually caused long before symptoms appear. The usefulness
      in different situations and the advantages and disadvantages of the various new
      tools for diagnosis of lymphatic filariasis are discussed. For loiasis,
      immunodiagnostic methods have not been very successful but repetitive DNA
      sequences in the Loa genome have been found to be species specific. Techniques
      based on them are particularly useful for diagnosing cases of occult infection
      without microfilaraemia. There have been no advances in the diagnosis of
      Mansonella perstans but both immunodiagnostic and PCR tests show promise in
      differentiating M. streptocerca, and the latter in differentiating M.ozzardi,
      from Onchocerca. In addition to the human filariae, the dog parasites Dirofilaria
      immitis and D. repens can also occur in humans but do not produce microfilariae
      in them. ELISAs and PCR probes have been devised and can usefully differentiate
      between pulmonary dirofilariasis and lung cancer.

PMID- 14587700
TI  - Solid-state electroluminescent devices based on transition metal complexes.
AB  - Transition metal complexes have emerged as promising candidates for applications
      in solid-state electroluminescent devices. These materials serve as
      multifunctional chromophores, into which electrons and holes can be injected,
      migrate and recombine to produce light emission. Their device characteristics are
      dominated by the presence of mobile ions that redistribute under an applied field
      and assist charge injection. As a result, an efficiency of 10 lm/W--among the
      highest efficiencies reported in a single layer electroluminescent device--was
      recently demonstrated. In this article we review the history of
      electroluminescence in transition metal complexes and discuss the issues that
      need to be addressed for these materials to succeed in display and lighting
      applications.

PMID- 14587701
TI  - Folic acid-conjugated nanostructured materials designed for cancer cell
      targeting.
AB  - Shell cross-linked nanoparticles (SCKs) constitute a unique class of materials
      with amphiphilic core-shell morphology; SCKs are characterised by their
      structural integrity and available functionality to attach receptor-recognising
      or receptor-specific ligands on the shell surface and, therefore, hold great
      potential in drug delivery applications; in an attempt to develop novel, cancer
      cell specific delivery vehicles, folate receptor targeted SCKs have been
      prepared.

PMID- 14587702
TI  - Assay amplification-multiple valent fluorophores.
AB  - The synthesis of a dendrimeric, internally quenched, fluorogenic peptide allowed
      signal amplification following enzymatic cleavage.

PMID- 14587703
TI  - Palladium-catalyzed allylic alkenylation of allylic alcohols with n-butyl
      acrylate.
AB  - Various allylic alcohols reacted with n-butyl acrylate in the presence of p
      toluenesulfonic anhydride and palladium catalysts to yield the corresponding n
      butyl 2,5-dienoates with high regioselectivity.

PMID- 14587704
TI  - Studies of the S1 state in a prototypical molecular wire using picosecond time
      resolved spectroscopies.
AB  - Picosecond time-resolved resonance Raman spectroscopy, TR3, reveals an intense
      acetylenic band in the S1 state of the prototypical molecular wire 1,4
      bis(phenylethynyl)benzene.

PMID- 14587705
TI  - Metal-directed self-assembly of bimetallic dithiocarbamate transition metal
      cryptands and their binding capabilities.
AB  - A novel family of redox-active dinuclear transition metal based cryptands self
      assembled from dithiocarbamate ligands has been synthesised; depending upon the
      nature of the spacer groups these new cryptand systems have been shown to
      electrochemically recognise the binding of cations or anions.

PMID- 14587706
TI  - Preparation of methyl (1R,2S,5S)- and (1S,2R,5R)-2-amino-5-tert-butyl
      cyclopentane-1-carboxylates by parallel kinetic resolution of methyl (RS)-5-tert
      butyl-cyclopentene-1-carboxylate.
AB  - Comparison of the kinetic and parallel kinetic resolutions of methyl (RS)-5-tert
      butyl-cyclopentene-1-carboxylate allows for the efficient synthesis of both
      (1R,2S,5S)- and (1S,2R,5R)-enantiomers of methyl 2-amino-5-tert-butyl
      cyclopentane-1-carboxylate.

PMID- 14587707
TI  - A supramolecular cup-and-ball C60-porphyrin conjugate system.
AB  - In addition to the ammonium-crown ether recognition, pi-stacking interactions
      between the C60 sphere and the porphyrin moiety have been evidenced in a
      supramolecular complex obtained from a porphyrin-crown ether conjugate and a
      fullerene derivative bearing an ammonium unit.

PMID- 14587708
TI  - Copper(II)-catalysed aerobic oxidation of primary alcohols to aldehydes.
AB  - [CuBr2(2,2'-bipyridine)] catalyses the selective and very mild aerobic oxidation
      of primary alcohols to aldehydes in acetonitrile:water (2:1) in the presence of
      2,2,6,6-tetramethylpiperidinyl-1-oxy (TEMPO) and a base as cocatalysts.

PMID- 14587709
TI  - Rapid screening by MALDI-TOF mass spectrometry to probe binding specificity at
      enzyme active sites.
AB  - The binding affinity of aspartate decarboxylase has been probed using MALDI-TOF
      spectrometry; adducts formed covalently in the active site were detected by MALDI
      TOF mass spectrometry after incubation of the enzyme with a range of potential
      ligands in the presence of NaCNBH3; this has highighted key structural features
      which will aid design of potential inhibitors.

PMID- 14587710
TI  - Determination of hydrogen concentration in ionic liquids and the effect (or lack
      of) on rates of hydrogenation.
AB  - The solubility of hydrogen and the corresponding Henry coefficients for 11 ionic
      liquids have been determined in situ at 100 atm H2 pressure and are much lower
      than expected; attempts to correlate the solubility of hydrogen in the ionic
      liquids with the rate of reaction for the hydrogenation of benzene to cyclohexane
      in these solvents have been made.

PMID- 14587711
TI  - Uranyl-salophen based ditopic receptors for the recognition of quaternary
      ammonium halides.
AB  - Uranyl-salophen complexes endowed with aromatic side arms behave as very
      efficient ditopic receptors towards tetralkylammonium halides as a result of a
      combination of Lewis acid-base and cation-pi interactions.

PMID- 14587712
TI  - The first liquid-crystalline, expanded porphyrins.
AB  - Aliphatic derivatives of hydrazinophyrin, a new type of tetrapyrrolic macrocycle
      prepared by the condensation of 2,5-diformylpyrroles with hydrazine, exhibit
      liquid crystalline properties as judged from polarising optical microscopy; these
      hydrazinophyrins appear to be the first mesogens derived from an expanded
      porphyrin core.

PMID- 14587713
TI  - H+, Na+ and K+ modulated lanthanide luminescent switching of Tb(III) based cyclen
      aromatic diaza-crown ether conjugates in water.
AB  - The cyclen based aromatic diaza-15-crown-5 and 18-crown-6 ether conjugates 1Tb
      4Tb were designed as luminescent switches for sodium and potassium where the
      delayed Tb(III) emission, occurring as line-like emission bands between 490-622
      nm, was 'switched on' upon recognition of these ions in pH 7.4 buffered water
      solution.

PMID- 14587714
TI  - The synthesis of tetra-acrylamido-calix[4]arene capsules.
AB  - Upper rim substituted tetra-acrylamido-calix[4]arenes have been synthesised using
      the palladium catalysed Heck reaction; the compounds display solvent dependent
      aggregation in solution to form dimeric capsules stabilised by only eight amide
      C=O-H-N hydrogen bonds and pi-pi interactions.

PMID- 14587715
TI  - Fluorescent supramolecular liquid crystalline polymers from nucleobase-terminated
      monomers.
AB  - While thymine or N6-(4-methoxybenzoyl)adenine terminated bis(4-alkoxy)
      substituted bis(phenylethynyl)benzene monomers show no liquid crystalline
      behaviour by themselves, mixing the complementary nucleobase monomers together
      results in the formation of thermotropic liquid crystalline phases.

PMID- 14587716
TI  - Separation, recovery and recycling of a fluorous-tagged nickel catalyst using
      fluorous solid-phase extraction.
AB  - Highly efficient separation, recovery and recycling of the fluorous-tagged
      catalyst, [Ni[F13C6C(O)CHC(O)C6F13]2], can be achieved with fluorous solid-phase
      extraction, after the Lewis acid catalysed synthesis of enaminodiones in
      conventional organic solvents.

PMID- 14587717
TI  - Self-asssembly of a molecular M8L12 cube having S6 symmetry.
AB  - Reaction of the bis-bidentate ligand L1, having two bidentate pyrazolyl-pyridine
      termini, with Co(II) or Zn(II) results in formation of the complexes
      [M8(L1)12]X16 (X = perchlorate or tetrafluoroborate); [Zn8(L1)2](ClO4)16 has been
      structurally characterised and is a cube with a metal ion at each corner, a
      bridging ligand along each edge, and an anion in the central cavity.

PMID- 14587718
TI  - Technomimetic molecules: synthesis of ruthenium(II) 1,2,3,4,5-penta(p
      bromophenyl)cyclopentadienyl hydrotris(indazolyl)borate, an organometallic
      molecular turnstile.
AB  - A short route to prepare a ruthenium complex with a pentaphenyl substituted
      cyclopentadienyl and a hydrotris(indazolyl)borate ligand is described: this
      complex can be seen as an organometallic molecular turnstile.

PMID- 14587719
TI  - Stable nitridorhenium(V) complexes with an N-heterocyclic carbene.
AB  - Nitridorhenium(V) complexes with the nucleophilic cyclocarbene 1,3,4-triphenyl
      1,2,4-triazol-5-ylidene have been synthesised and are the first representatives
      of a new class of high-valent metallocarbenes.

PMID- 14587720
TI  - Rhodium-catalyzed Heck-type reaction of arylboronic acids with alpha,beta
      unsaturated esters: tuning beta-hydrogen elimination vs. hydrolysis of
      alkylrhodium species.
AB  - The elusive rhodium-catalyzed Heck-type coupling of arylboronic acids with
      alpha,beta-unsaturated esters is effected using rhodium chloride as catalyst,
      indicating the hydrolysis of Rh-C bond could be finely tuned by the steric
      environment around rhodium.

PMID- 14587721
TI  - Ab initio predictions of ferroelectric ternary fluorides with the LiNbO3
      structure.
AB  - First-principles periodic density-functional theory calculations suggest ternary
      fluorides LiMgF3, NaCaF3 and LiNiF3 should adopt the ferroelectric LiNbO3
      structure at low temperatures; LiMgF3 and LiNiF3 are predicted to have negative
      enthalpies of formation from the binary fluorides.

PMID- 14587722
TI  - Perylene nanotubes fabricated by the template method.
AB  - Aligned organic nanotubes of perylene with uniform diameters, lengths and wall
      thicknesses were fabricated via a simple immersion technique using a porous
      alumina membrane as the template.

PMID- 14587724
TI  - Synthesis and luminescence behaviour of novel heterodecanuclear silver(I)
      rhenium(I) alkynyl complexes. X-ray crystal structures of [Ag6(mu-dppm)4[mu3
      C[triple bond]CC[triple bond]C-Re(Me2bpy)(CO)3]4](PF6)2 and [Ag6(mu-dppm)4[mu3
      C[triple bond]CC[triple bond]C-Re(Br2phen)(CO)3]4](PF6)2.
AB  - A novel series of luminescent heterodecanuclear mixed-metal alkynyl complexes,
      [Ag6(mu-dppm)4[mu3-C[triple bond]CC[triple bond]C-Re(N--N)(CO)3]4](PF6)2, (N--N =
      tBu2bpy, Me2bpy, phen, Br2phen), have been successfully synthesized; the X-ray
      crystal structures of [Ag6(mu-dppm)4[mu3-C[triple bond]CC[triple bond]C
      Re(Me2bpy)(CO)3]4](PF6)2 and [Ag6(mu-dppm)4[mu3-C[triple bond]CC[triple bond]C
      Re(Br2phen)(CO)3]4](PF6)2 have also been determined.

PMID- 14587723
TI  - Surfactant solvation effects and micelle formation in ionic liquids.
AB  - The formation of micelles in 1-butyl-3-methyl imidazolium chloride (BMIM-Cl) and
      hexafluorophosphate (BMIM-PF6) were explored using different surfactants and the
      solvation behavior of the new micellar-ionic liquid solutions examined using
      inverse gas chromatography.

PMID- 14587725
TI  - Proline-catalysed asymmetric amination of alpha,alpha-disubstituted aldehydes:
      synthesis of configurationally stable enantioenriched alpha-aminoaldehydes.
AB  - Proline-catalysed amination of alpha,alpha-disubstituted racemic aldehydes with
      azodicarboxylates proceeds smoothly to give configurationally stable scalemic
      aldehydes and oxazolidinones in up to 86% ee.

PMID- 14587726
TI  - Regioselective synthesis of 1,2,3-triazole derivatives via 1,3-dipolar
      cycloaddition reactions in water.
AB  - Reaction of an arylacetylene with an azide in hot water gave 1,4-disubstituted
      1,2,3-triazoles in high yields, while similar reaction between a terminal
      aliphatic alkyne and an azide (except m-nitroazidobenzene) afforded a mixture of
      regioisomers with the ratio of 1,4- to 1,5-isomers ranging from 3:1 to 28.6:1.
      Reactions of m-nitroazidobenzene with either arylalkynes or aliphatic alkynes
      formed only 1,4-disubstituted derivatives in excellent yields.

PMID- 14587727
TI  - Metal-assisted red light-induced efficient DNA cleavage by dipyridoquinoxaline
      copper(II) complex.
AB  - Complete cleavage of double stranded pUC19 DNA by the complex
      [Cu(dpq)2(H2O)](ClO4)2 (dpq, dipyridoquinoxaline) has been observed on
      irradiation at 694 nm from a pulsed ruby laser, assisted by the metal d-band
      transition as well as the quinoxaline triplet states in the absence of any
      external additives.

PMID- 14587728
TI  - Indium triflate-catalysed double addition of heterocyclic arenes to alkynes.
AB  - Indium triflate was found to be a prominent catalyst for addition of heterocyclic
      arenes to alkynes to afford 2:1 adducts, where two heterocyclic arenes
      regioselectively attacked the same carbon atom of alkynes.

PMID- 14587729
TI  - Creating monolayers and thin films of a novel bis(alkyl) substituted asymmetrical
      polyoxotungstate, [[CH3(CH2)11Si]2OSiW11O39]4- using the Langmuir-Blodgett
      technique.
AB  - A bis(alkyl) substituted, asymmetric polyoxometalate
      [[CH3(CH2)3]4N]4[[CH3(CH2)11Si]2OSiW11O39], was prepared and incorporated into
      monolayer and multilayer thin films using Langmuir-Blodgett techniques.

PMID- 14587730
TI  - Neutral nido-heteroboranes with non ionisable hydrogen as arenes in coordination.
AB  - Designed ligands have been synthesised to produce the first arene-like
      metallacarborane. For arene-like coordination the number of electronegative
      elements on the coordinating site must be kept to a minimum. Choosing ligands
      with bulky substituents on the heteroatom allows easy rearrangement and arene
      like coordination. This is more hampered the higher the number of hetereoatoms to
      be re-located.

PMID- 14587731
TI  - Novel CuI/tributyl phosphine catalyst system for amination of aryl chlorides.
AB  - A simple and efficient methodology for the synthesis of triarylamines from aryl
      chlorides in a single step has been demonstrated using a novel CuI/tributyl
      phosphine catalyst system with high activity and selectivity (80-87% yield).

PMID- 14587732
TI  - Amidate complexes of titanium and zirconium: a new class of tunable precatalysts
      for the hydroamination of alkynes.
AB  - A series of bis(amidate)group 4-bis(amido) complexes have been prepared,
      characterized and have been shown to be highly tunable precatalysts for both the
      intra- and intermolecular hydroamination of alkynes.

PMID- 14587734
TI  - A reusable, insoluble polymer-bound bis(oxazoline) (IPB-box) for highly
      enantioselective heterogeneous cyclopropanation reactions.
AB  - A reusable, insoluble polystyrene-supported bis(oxazoline) was developed,
      affording e.e.s > 90% in the heterogeneous enantioselective cyclopropanation of
      styrene and 1,1-disubstituted alkenes with ethyl diazoacetate.

PMID- 14587733
TI  - Synthesis of (+)-nocardione A--use of formal radical cyclization onto a benzene
      ring.
AB  - Juglone (7) was converted into enone 13; this underwent radical cyclization to
      afford 15, which was aromatized to 16 and elaborated into (+)-nocardione A (1),
      the enantiomer of the naturally-occurring tyrosine phosphatase inhibitor (-)
      nocardione A (2).

PMID- 14587736
TI  - Disproportionation reaction of NO2/N2O4 with a Ru(II) porphyrin.
AB  - A Ru(II) porphyrin rapidly reacts with NO2/N2O4 with the formation of a stable
      Ru(II) nitrosyl nitrato complex.

PMID- 14587735
TI  - Model systems for flavoenzyme activity: flavin-functionalised SAMs as models for
      probing redox modulation through hydrogen bonding.
AB  - We report the fabrication of flavin-functionalised self-assembled monolayers upon
      gold electrodes and their subsequent redox modulation via hydrogen bonding to 2,6
      diethylamidopyridine.

PMID- 14587737
TI  - Ordered mesoporous organic-inorganic hybrid materials containing microporous
      functional calix[8]arene amides.
AB  - Ordered mesoporous organic-inorganic hybrid materials containing microporous
      functional calix[8]arene amides have been synthesized and characterized for the
      first time, and are shown to be effective in removal of trace humic acid
      contaminant from water.

PMID- 14587738
TI  - Bidentate ligands formed by self-assembly.
AB  - A novel supramolecular strategy to prepare bidentate ligands via the assembly of
      functionalised monomeric ligands on a dimeric zinc(II) porphyrin template is
      presented; the assembled bidentate ligands show chelating behaviour and their
      rhodium complexes display enhanced selectivity in the hydroformylation compared
      to the non-template analogue.

PMID- 14587739
TI  - Sulfoxide-directed thermal intramolecular [4 + 2] cycloadditions between 2
      sulfinyl butadienes and unactivated alkynes.
AB  - 2-Sulfinyl butadienes tethered to unactivated alkynes undergo a facile thermal
      intramolecular Diels-Alder cycloaddition, often at room temperature, to produce
      cyclohexa-1,4-dienes with good selectivities, in high yields, and preserving the
      valuable vinyl sulfoxide functionality.

PMID- 14587740
TI  - Hexagonal CdTe nanoparticles of various morphologies.
AB  - The present communication describes a new, organometallic synthesis method for
      CdTe nanocrystals using cadmium stearate as cadmium source; nanocrystals of
      different morphologies like spheres, rods and spikes were prepared and the
      metastable crystallographic hexagonal phase was stabilised in all samples.

PMID- 14587742
TI  - Palladium-catalyzed stereospecific epoxide-opening reaction of gamma,delta-epoxy
      alpha,beta-unsaturated esters with an alkylboronic acid leading to gamma,delta
      vicinal diols with double inversion of the configuration.
AB  - A palladium-catalyzed stereospecific epoxide-opening reaction of gamma,delta
      epoxy-alpha,beta-unsaturated esters with an alkylboronic acid leading to
      gamma,delta-vicinal diols is described, which proceeds with retention of the
      configuration, i.e., via two consecutive S(N)2 processes, to afford the
      corresponding gamma,delta-cyclic boronates in high yields.

PMID- 14587741
TI  - Improving the performance of solid-state dye-sensitized solar cell using MgO
      coated TiO2 nanoporous film.
AB  - An ultrathin overlayer of MgO on TiO2 is shown to drastically improve the
      stability of solid-state dye-sensitized solar cell using CuI as a hole conductor
      in addition to solar energy conversion efficiency.

PMID- 14587743
TI  - Expanding the repertoire of pyrrolidyl PNA analogues for DNA/RNA hybridization
      selectivity: aminoethylpyrrolidinone PNA (aepone-PNA).
AB  - New PNA analogues derived from aminoethylpyrrolidin-5-one backbone show
      stabilization of aepone-PNA:DNA hybrids and destabilization of the corresponding
      RNA hybrids compared to unmodified PNA.

PMID- 14587744
TI  - Synthesis of heparin-like oligosaccharides on a soluble polymer support.
AB  - Based on previously developed solution phase chemistry, an effective general
      approach to the synthesis of heparin-like oligosaccharides on a soluble polymer
      support is reported.

PMID- 14587745
TI  - Novel preparation of nanocrystalline magnesia-supported caesium-promoted
      ruthenium catalyst with high activity for ammonia synthesis.
AB  - A caesium-promoted ruthenium catalyst supported on nanocrystalline magnesia with
      high activity for ammonia synthesis was conveniently prepared by using hydrated
      ruthenium trichloride and hexahydrate magnesium nitrate as precursors, whereas
      dechlorination post-treatment and ready-made magnesia were not necessary.

PMID- 14587746
TI  - Palladium(II) acetate mediated oxidative cyclization of omega-unsaturated alpha
      cyano ketones. A facile methylenecyclopentane annulation process.
AB  - A highly efficient methylenecyclopentane annulation process has been developed
      based on the Pd(II)-mediated oxidative cyclization of omega-unsaturated alpha
      cyano ketones, readily accessed via the Michael addition of 3-butenylmagnesium
      bromide with 2-cyano-2-cycloalkenones.

PMID- 14587747
TI  - Substitution of a bridgehead bromide by primary organolithium reagents.
AB  - The reaction of ketone 1 with primary organolithium reagents in THF/HMPA affords
      not the expected carbonyl addition product but the product of bromide
      substitution, in reasonable yield.

PMID- 14587748
TI  - Organized assemblies of thiol-terpyridine and thiophenol on gold surfaces:
      preferential composition of mixed species evidenced.
AB  - Mixed self-assembled monolayers based on thiol-terpyridine and thiophenol
      molecules on gold surfaces show a tendency to form films whose composition is
      almost independent of the molar fraction of the components in the starting
      solution, and this indicates the formation of particularly stable assemblies.

PMID- 14587749
TI  - Use of a fluorous bridge for diffusion controlled uptake of molecular chlorine in
      chlorine addition to alkenes.
AB  - Fluorous solvent was used for passive transport of molecular chlorine from one
      side of the U-tube to the other, where addition of chlorine to alkenes was
      quantitative and diffusion controlled.

PMID- 14587750
TI  - Controllable CVD route to CoS and MnS single-crystal nanowires.
AB  - CoS and MnS nanowires were prepared through a simple chemical vapor deposition
      process. The adopted synthetic route is expected to be applicable for the
      synthesis of other metal sulfide semiconductor nanowires.

PMID- 14587751
TI  - Preparation of reactive surfaces by electrografting.
AB  - The electrografting process has been applied to a new monomer in order to induce
      reactivity to the surface of various conducting substrates which are then
      appropriate for the anchoring of a large variety of molecules (catalysts,
      proteins, amino-polymers etc.).

PMID- 14587752
TI  - Control of self-aldol condensation by pressure manipulation under compressed CO2.
AB  - Under supercritical CO2 conditions, simple adjustment of the pressure was found
      to successfully control the ratio of aldol to enal product in the self-aldol
      condensation of aldehyde, in which the enal product was obtained in a maximum
      selectivity of 94% at the critical pressure of 12MPa, whereas 85% selectivity to
      the aldol product was achieved at the subcritical region.

PMID- 14587753
TI  - Preparation of organic-inorganic composites containing rod-like phthalocyanine
      polymers.
AB  - Sol-gel polymerization of tetraethoxysilane in the presence of amphiphilic
      phthalocyanine polymer 2 produced organic-inorganic composites with the rod-like
      phthalocaynine polymers incorporated within ordered hexagonal channels.

PMID- 14587754
TI  - Redox-triggered on/off coordination of a bridgehead nitrogen donor in a tripodal
      iron complex.
AB  - We report the unprecedented redox-triggered on/off coordination of a bridgehead
      nitrogen donor in an iron complex of the tripodal ligand 2,2',2''
      nitrilotribenzoate; the complex is an efficient redox catalyst for H2O2 oxidation
      of hydroquinone while complexes of related ligands are inactive.

PMID- 14587755
TI  - Macrocyclic diiminodipyrromethane complexes: structural analogues of Pac-Man
      porphyrins.
AB  - The complexation of palladium(II) by a unique family of [2+2]
      diiminodipyrromethane macrocycles yields compounds that adopt structures
      reminiscent of Pac-Man porphyrins.

PMID- 14587756
TI  - Spectrum of three-dimensional photonic quantum-ring microdisk cavities:
      comparison between theory and experiment.
AB  - The spectrum of a three-dimensional Rayleigh-Fabry-Perot microdisk cavity of a
      photonic quantum-ring laser is analyzed for angle-dependent emission modes. It is
      shown that joint consideration of the Fabry-Perot resonance condition and the
      whispering-gallery mode boundary condition explains the emitting angles and
      spectral distribution of the cavity modes well.

PMID- 14587757
TI  - Entangled double-helix phase.
AB  - We present a novel phase with an entangled double-helix structure. Beams with
      this phase have the same transverse patterns as those of interference between two
      doughnut beams. This proposed method allows a complete set of the superpositions
      of the doughnut modes or the orbital angular momentum states with different
      topological orders to be obtained. Furthermore, it introduces a simple continuous
      and controlled rotation of the transverse patterns by use of a spatial light
      modulator. It can be used to form a three-dimensional structure by three
      dimensional trapping in an optical tweezers setup or to study the quantum
      characteristics of an optical vortex.

PMID- 14587758
TI  - Dynamic optical manipulation with a higher-order fractional bessel beam generated
      from a spatial light modulator.
AB  - Higher-order Bessel beams have been demonstrated to have the ability to trap and
      rotate low- and high-index particles simultaneously [Phys. Rev. A 66, 063402
      (2002)]. The rotation and trapping is caused by the presence of orbital angular
      momentum arising from its azimuthal phase variation (that changes at integer
      multiples of 2pi) and the concentric rings of the Bessel mode. We demonstrate for
      the first time to our knowledge a branch from the family of higher-order Bessel
      beams that has fractional azimuthal variation at its beam axis. This new family
      of laser beams has the ability to perform dynamic optical manipulation with
      dynamic control of a spatial light modulator. Furthermore, we take the
      opportunity to explore the propagation characteristics of higher-order Bessel
      beams for which the azimuthal phase changes at noninteger multiples of 2pi.

PMID- 14587759
TI  - Resonant coupling of surface plasmons to radiation modes by use of dielectric
      gratings.
AB  - Efficient outcoupling of surface-plasma waves to radiation modes by use of
      dielectric diffraction gratings on a flat metallic surface is discussed. The
      dielectric gratings, which have a surface-relief structure with only several tens
      of nanometers in peak-to-trough height on a flat metal surface, can efficiently
      extract radiation modes propagating in free space from the surface-plasmon modes.
      An outcoupling efficiency of 50% is estimated with the rigorous coupled-wave
      diffraction theory, and it is confirmed by the experiment.

PMID- 14587760
TI  - Reverse propagation of femtosecond pulses in optical fibers.
AB  - We present a numerical technique for reversing femtosecond pulse propagation in
      an optical fiber, such that given any output pulse it is possible to obtain the
      input pulse shape by numerically undoing all dispersion and nonlinear effects.
      The technique is tested against experimental results, and it is shown that it can
      be used for fiber output pulse optimization in both the anomalous and normal
      dispersion regimes.

PMID- 14587761
TI  - Double-helix chiral fibers.
AB  - A polarization-selective photonic stop band is demonstrated in a new chiral fiber
      structure with double-helix symmetry. The stop band exists for only circularly
      polarized radiation with the same handedness as the structure and is centered at
      a wavelength in the fiber equal to the fiber pitch. When one part of the chiral
      fiber is twisted about its axis, a localized mode is produced, which can be tuned
      across the gap by changing the twist angle. Observations in single-mode fibers
      are in good agreement with one-dimensional simulations of a dispersive
      cholesteric material. At higher frequencies, however, we find a sharp onset of a
      broad polarization-selective scattering band, which is not present in one
      dimensional simulations.

PMID- 14587762
TI  - Modal cutoff and the V parameter in photonic crystal fibers.
AB  - We address the long-standing unresolved problem concerning the V parameter in a
      photonic crystal fiber. In formulating the parameter appropriate for a core
      defect in a periodic structure, we argue that the multimode cutoff occurs at a
      wavelength lambda* that satisfies VPCF(lambda*) = pi. By comparing this approach
      with numerics and recent cutoff calculations we confirm this result.

PMID- 14587763
TI  - Experimental investigation of cutoff phenomena in nonlinear photonic crystal
      fibers.
AB  - Modal cutoff is investigated experimentally in a series of high-quality nonlinear
      photonic crystal fibers. We demonstrate a suitable measurement technique with
      which to determine the cutoff wavelength and verify the technique by inspecting
      the near field of the modes that may be excited below and above the cutoff. We
      observe a double-peak structure in the cutoff spectra, which is attributed to
      splitting of the higher-order modes. The cutoff is measured for seven different
      fiber geometries with different pitches and relative hole sizes, and very good
      agreement with recent theoretical work is found.

PMID- 14587764
TI  - Loss analysis of air-core photonic crystal fibers.
AB  - By using a multipole moment approach, we analyze the loss of an air-core photonic
      crystal fiber and demonstrate that it is possible reduce the transmission loss
      that is due to photon radiation leakage through the photonic crystal cladding to
      a level below 0.01 dB/km, with eight rings of air holes. An analogy is drawn
      between air-core photonic crystal fiber modes and Bragg fiber modes. The
      influence of material absorption in the silica glass is discussed.

PMID- 14587765
TI  - Efficient single-mode Brillouin fiber laser for low-noise optical carrier
      reduction of microwave signals.
AB  - We experimentally demonstrate efficient optical carrier reduction of microwave
      signals with a single-mode 1.5-microm wavelength Brillouin all-fiber ring laser.
      Because of the tunable optical coupling, the lasing threshold of the short-length
      (20-m) fiber cavity is lower than 5 mW, and high conversion efficiencies (up to
      60%) are obtained at any pump power up to approximately 200 mW. Using the single
      mode Stokes beam as a seed for the stimulated Brillouin scattering process allows
      up to 40-dB optical carrier depletion with almost no added noise for an optically
      carried microwave signal at 6 GHz. In addition, using this resonator, we provide
      evidence of generation of high-spectral-purity beatnotes.

PMID- 14587766
TI  - Short-pulse, all-fiber, Raman laser with dispersion compensation in a holey
      fiber.
AB  - The use of Raman gain in conventional fiber followed by dispersion compensation
      in a holey fiber in a synchronously pumped laser configuration allowed
      compression by a factor of 8.5 of output pulses at a selected wavelength with
      respect to the pump pulses. We obtained 2-ps output pulses at 1.14 microm from a
      totally fiber-integrated laser pumped with 17-ps pulses at 1 microm. Higher pulse
      compression should be possible with nonlinear chirp compensation. Ultrashort
      pulse, all-fiber Raman lasers at wavelengths shorter than 1.3 microm are
      feasible.

PMID- 14587767
TI  - Use of multicanonical Monte Carlo simulations to obtain accurate bit error rates
      in optical communications systems.
AB  - We apply the multicanonical Monte Carlo (MMC) method to compute the probability
      distribution of the received voltage in a chirped return-to-zero system. When
      computing the probabilities of very rare events, the MMC technique greatly
      enhances the efficiency of Monte Carlo simulations by biasing the noise
      realizations. Our results agree with the covariance matrix method over 20 orders
      of magnitude. The MMC method can be regarded as iterative importance sampling
      that automatically converges toward the optimal bias so that it requires less a
      priori knowledge of the simulated system than importance sampling requires. A
      second advantage is that the merging of different regions of a probability
      distribution function to obtain the entire function is not necessary in many
      cases.

PMID- 14587768
TI  - Transmissive in-fiber Fabry-Perot etalons as tunable dispersion compensators and
      dispersion-slope compensators.
AB  - We report for what is believed to be the first time the use of transmissive fiber
      Bragg grating-based Fabry-Perot etalons for tunable dispersion compensation and
      dispersion-slope compensation. The resulting device has a number of advantages,
      such as low cost, ease of fabrication, full optical fiber compatibility, and
      simplicity.

PMID- 14587769
TI  - Time-averaged digital holography.
AB  - We demonstrate that it is possible to study the modal structures of a vibrating
      object with digitally recorded holograms by use of the time-averaging principle.
      We investigate the numerical reconstruction from a theoretical point of view, and
      we show that the numerically reconstructed object from a digital hologram is
      modulated by the zeroth-order Bessel function. Results of experiments in time
      averaged digital holography are presented.

PMID- 14587770
TI  - Analysis of adiabatic coupling between photonic crystal single-line-defect and
      coupled-resonator optical waveguides.
AB  - A detailed analysis of adiabatic coupling between conventional photonic crystal
      single-line-defect and coupled-resonator optical waveguides is reported.
      Adiabatic coupling by progressive variation of the radii of the spacing defects
      between cavities is investigated. Flat transmission spectra with coupling
      efficiencies greater than 90% are achieved in a broad frequency range with short
      coupling lengths. Moreover, we find that flat transmission at low frequencies
      requires longer coupling lengths partly because the requirements imposed for
      adiabatic transmission in photonic crystals are violated.

PMID- 14587771
TI  - Nonreciprocal reflection of a subwavelength hole array.
AB  - We present measurements of the wavelength-dependent reflectivity of a
      subwavelength metal hole array on a glass substrate. We compare the observed
      resonant structures with those found in transmission and note a nonreciprocity
      under illumination from the air versus the glass side. This can be used to verify
      on which interface the surface plasmons are resonantly excited and to estimate
      the losses in the subwavelength channels.

PMID- 14587772
TI  - Three-dimensional photonic-crystal emission through thermal excitation.
AB  - A three-dimensional tungsten photonic crystal is thermally excited and shown to
      emit light at a narrow band, lambda = 3.3-4.25 microm. The emission is
      experimentally observed to exceed that of the free-space Planck radiation over a
      wide temperature range, T = 475-850 K. It is proposed that an enhanced density of
      state associated with the propagating electromagnetic Bloch waves in the photonic
      crystal is responsible for this experimental finding.

PMID- 14587773
TI  - Saturated-absorption spectroscopy: eliminating crossover resonances by use of
      copropagating beams.
AB  - We demonstrate a new technique for saturated-absorption spectroscopy by use of
      copropagating beams that does not have the problem of crossover resonances. The
      pump beam is locked to a transition, and its absorption signal is monitored while
      the probe beam is scanned. As the probe comes into resonance with another
      transition, the pump absorption is reduced and the signal shows a Doppler-free
      dip. We use this technique to measure hyperfine intervals in the D2 line of 85Rb
      with a precision of 70 kHz and to resolve hyperfine levels in the D2 line of 39K
      that are less than 10 MHz apart.

PMID- 14587774
TI  - Dual-axes confocal microscopy with post-objective scanning and low-coherence
      heterodyne detection.
AB  - We present a dual-axes confocal microscope that employs postobjective scanning
      and low-coherence heterodyne detection to collect vertical cross-sectional images
      from biological tissue with high axial resolution, reduced noise from scattered
      light, deep tissue penetration, and a large dynamic range. This architecture can
      be scaled down to millimeter dimensions with microelectromechanical systems
      technology for performance of in vivo optical biopsy.

PMID- 14587775
TI  - Multiphoton multifocal microscopy exploiting a diffractive optical element.
AB  - Multiphoton multifocal microscopy (MMM) usually has been achieved through a
      combination of galvo scanners with microlens arrays, with rotating disks of
      microlens arrays, and cascaded beam splitters with asynchronous rastering of
      scanning mirrors. Here we describe the achievement of a neat and compact MMM by
      use of a high-diffraction-efficiency diffractive-optic element that generates a
      multiple-spot grid of uniform intensity to achieve higher fidelity in imaging of
      live cells at adequate speeds.

PMID- 14587776
TI  - Spectral shaping to improve the point spread function in optical coherence
      tomography.
AB  - We demonstrate inhibition of the sidelobes of the axial point spread function in
      optical coherence tomography by shaping the power spectrum of the light source
      with a remaining power of 4.54 mW. A broadband amplified spontaneous emission
      source radiating at 1565 +/- 40 nm is employed in a free-space optical coherence
      tomography system. The axial point spread functions before and after optical
      spectral shaping are presented. Results show that spectral shaping of the source
      can inhibit sidelobes of the point spread function up to 12.9 dB, with an
      associated small increase of 2.2 dB in noise floor in the far field. The effect
      of spectral shaping on axial resolution is demonstrated according to three
      metrics. Image quality improvement is also illustrated with optical coherence
      tomography images of an onion before and after spectral shaping.

PMID- 14587777
TI  - Large depth-of-focus time-multiplexed three-dimensional integral imaging by use
      of lenslets with nonuniform focal lengths and aperture sizes.
AB  - Conventional integral-imaging systems utilize lenslet arrays with fixed focal
      lengths and aperture sizes. We propose a time-multiplexed integral-imaging method
      that enhances both the depth of focus and the resolution of a three-dimensional
      image by displaying it with an array of lenslets with different focal lengths and
      aperture sizes. The nonuniform lenslet parameters (focal lengths and aperture
      sizes) for our method are calculated. Our theoretical analysis indicates that
      significant improvements in both depth of focus and resolution can be obtained
      with the proposed technique.

PMID- 14587778
TI  - Order-N sparse minimum-variance open-loop reconstructor for extreme adaptive
      optics.
AB  - A scalable sparse minimum-variance open-loop wave-front reconstructor for extreme
      adaptive optics (ExAO) systems is presented. The reconstructor is based on
      Ellerbroek's sparse approximation of the wave-front inverse covariance matrix [J.
      Opt. Soc. Am. A 19, 1803 (2002)]. The baseline of the numerical approach is an
      iterative conjugate gradient (CG) algorithm for reconstructing a spatially
      sampled wave front at N grid points on a computational domain of size equal to
      the telescope's primary mirror's diameter D that uses a multigrid (MG)
      accelerator to speed up convergence efficiently and enhance its robustness. The
      combined MGCG scheme is order N and requires only two CG iterations to converge
      to the asymptotic average Strehl ratio (SR) and root-mean-square reconstruction
      error. The SR and reconstruction squared error are within standard deviation with
      figures obtained from a previously proposed MGCG fast-Fourier-transform based
      minimum-variance reconstructor that incorporates the exact wave-front inverse
      covariance matrix on a computational domain of size equal to 2D. A cost
      comparison between the present sparse MGCG algorithm and a Cholesky factorization
      based algorithm that uses a reordering scheme to preserve sparsity indicates that
      the latter method is still competitive for real-time ExAO wave-front
      reconstruction for systems with up to N approximately equal to 10(4) degrees of
      freedom because the update rate of the Cholesky factor is typically several
      orders of magnitude lower than the temporal sampling rate.

PMID- 14587779
TI  - Two-photon fluorescence scanning near-field microscopy based on a focused
      evanescent field under total internal reflection.
AB  - We present two-photon fluorescence near-field microscopy based on an evanescent
      field focus produced by a ring beam under total internal reflection. The
      evanescent field produced by this method is focused by a high-numerical-aperture
      objective, producing a tightly confined volume that can effectively induce two
      photon excitation. The imaging system is characterized by the two-photon-excited
      images of the nanocrystals, which show that the focused evanescent field is split
      into two lobes because of the enhancement of the longitudinal polarization
      component at the focus. This feature is confirmed by the theoretical prediction.
      Unlike other two-photon near-field probes, this method does not have the heating
      effect and requires no control mechanism of the distance between a sample and the
      probe.

PMID- 14587780
TI  - Ho:YAG laser intracavity pumped by a diode-pumped Tm:YLF laser.
AB  - We report a compact Ho:YAG laser that is intracavity pumped by a diode-pumped
      Tm:YLF laser. Both lasers exhibit pulse mode behavior. Operating both crystals at
      room temperature (25 degrees C), we obtained 1.6 W of average output at 2.09
      microm from the Ho:YAG laser for 15.4 W of diode power incident upon the Tm:YLF
      rod and a slope efficiency of 21%.

PMID- 14587781
TI  - Compact and efficient kinetically enhanced copper-vapor lasers of high (100-W)
      average power.
AB  - We report on severalfold increases in the output power of kinetically enhanced
      copper-vapor lasers operating in a regime of high specific input power and
      reduced tube insulation. Three laser tubes, of length 1 m and bore diameters
      17.5, 25, and 32 mm, were investigated at constant input power. Output power of
      104 W at 1.4% wall-plug efficiency was obtained for the largest tube. When the
      bore diameter was decreased to 17.5 mm, the output power and efficiency remained
      high (90 W at 1.0% efficiency), whereas the specific output power increased
      threefold. The output powers were as much as fivefold higher than those of
      previous small-scale (i.e., <25-mm-diameter) copper lasers of any type.

PMID- 14587782
TI  - Lateral and longitudinal coupled waveguides in semiconductor lasers.
AB  - A semiconductor laser including two laterally coupled waveguides, in which one of
      the waveguides includes a partially reflecting surface (an internal mirror)
      between its facets, is analyzed. The internal mirror inserts longitudinal
      coupling into the system. The spectrum of the Fabry-Perot modes exhibits
      modulation in the gain required for lasing threshold, with a periodicity that
      depends on the longitudinal position of the internal mirror. The combined coupled
      cavity effect may explain the observed gain spectrum in GaN lasers.

PMID- 14587783
TI  - Controlled switching of discrete solitons in waveguide arrays.
AB  - We suggest an effective method for controlling nonlinear switching in arrays of
      weakly coupled optical waveguides. We demonstrate digitized switching of a narrow
      input beam for as many as 11 waveguides in the engineered waveguide arrays.

PMID- 14587784
TI  - Engineering the nonlinear phase shift.
AB  - We treat the nonlinear phase shift response in the weak perturbation limit as a
      linear digital filter that can be synthesized into the values of its poles and
      zeros and mapped onto an optical architecture. This procedure results in a
      significant enhancement in the nonlinear sensitivity with a response that is
      robust to frequency changes within the filter passband. A precompensation
      technique can be used to reduce distortions under strongly driven nonlinear
      operation to achieve a larger phase shift. We also show that nonlinear
      sensitivity improves with increasing filter group delay and can be increased
      within constant linear bandwidth by use of higher-order filters.

PMID- 14587785
TI  - Efficient anti-Stokes generation through phase-matched four-wave mixing in higher
      order modes of a microstructure fiber.
AB  - Phase-matched four-wave mixing in higher-order modes of microstructure fibers
      allows unprecedentedly high efficiencies of anti-Stokes frequency conversion to
      be achieved for subnanojoule femtosecond laser pulses. 70-fs pulses of 790-nm
      radiation were used to generate an anti-Stokes component at 520-530 nm in a
      higher-order mode of a microstructure fiber with a 4.8-microm core. The maximum
      ratio of the anti-Stokes signal energy to the energy of the pump component in the
      output spectrum is estimated as 1.7.

PMID- 14587787
TI  - Coupled-mode theory of the Raman effect in silicon-on-insulator waveguides.
AB  - Coupled-mode theory is used to calculate Raman gain and spontaneous efficiency in
      silicon waveguides with cross-sectional areas ranging from 0.16 to 16 microm2. We
      find a monotonic increase in the Raman gain as the waveguide cross section
      decreases for the range of dimensions considered. It is also found that mode
      coupling between the Stokes modes is insignificant, and thus polarization
      multiplexing is possible. The results also demonstrate that for submicrometer
      waveguide dimensions the Einstein relation between spontaneous efficiency and
      stimulated gain no longer holds.

PMID- 14587786
TI  - Nonlinear femtosecond pulse compression at high average power levels by use of a
      large-mode-area holey fiber.
AB  - We demonstrate that nonlinear fiber compression is possible at unprecedented
      average power levels by use of a large-mode-area holey (microstructured) fiber
      and a passively mode-locked thin disk Yb:YAG laser operating at 1030 nm. We
      broaden the optical spectrum of the 810-fs pump pulses by nonlinear propagation
      in the fiber and remove the resultant chirp with a dispersive prism pair to
      achieve 18 W of average power in 33-fs pulses with a peak power of 12 MW and a
      repetition rate of 34 MHz. The output beam is nearly diffraction limited and is
      linearly polarized.

PMID- 14587788
TI  - Synchronously pumped CdSe optical parametric oscillator in the 9-10 microm
      region.
AB  - Continuous mode-locked operation of a singly resonant, synchronously pumped
      optical parametric oscillator (SPOPO) based on CdSe has produced idler output
      tuned over the range of 9.1-9.7 microm, the longest wavelength generated so far
      to our knowledge from a SPOPO. Average idler powers as high as approximately 70
      mW are generated in the crystal. Tandem pumping with a diffraction-grating-tuned
      parametric oscillator in periodically poled lithium niobate provides a convenient
      and agile means of tuning the noncritically phase-matched CdSe device. The
      absence of any detrimental thermal effects in the CdSe crystal suggests that
      significant further power scaling should be possible, with idler tuning ranges
      extendable to cover 8-12 microm.

PMID- 14587789
TI  - Complete experimental characterization of the influence of parametric four-wave
      mixing on stimulated Raman gain.
AB  - We present what is to our knowledge the first complete measurement of the
      dependence of Raman gain on chromatic dispersion, fully revealing the influence
      of parametric four-wave mixing on stimulated Raman scattering. In particular, a
      threefold increase of the Raman gain is observed under phase-matching conditions,
      in excellent agreement with theoretical predictions. Our experiments, which were
      performed in a photonic crystal fiber, demonstrate that these unique fibers can
      be exploited to boost the performances of fiber Raman amplifiers.

PMID- 14587790
TI  - Highly efficient blue-light generation from a compact, diode-pumped femtosecond
      laser by use of a periodically poled KTP waveguide crystal.
AB  - We present a simplified, potentially portable, and highly efficient blue-light
      source from a periodically poled KTP waveguide crystal with a compact femtosecond
      Cr:LiSAF laser. This light source generates 5.6 mW of blue average output power
      at 424 nm with 27 mW of incident fundamental in a single-pass extracavity
      arrangement at room temperature. The overall system efficiency of electrical
      power to blue light is 0.5%, and the internal second-harmonic generation
      conversion efficiency is as high as 37%. The slope efficiency of 5.5% pJ(-1) at
      low pulse energies is, to our knowledge, the highest slope efficiency yet
      reported for frequency conversion into the blue spectral region.

PMID- 14587791
TI  - Depositing light in a photonic stop gap by use of Kerr nonlinear microresonators.
AB  - We show theoretically that it is possible to trap light in a microresonator
      structure by use of four-wave mixing. The efficiency of the parametric process is
      substantially increased by the high group delay of light inside the structure.
      The energy that is trapped has a half-life of approximately 500 ps in the
      presence of both linear and nonlinear loss in the channel waveguides and
      resonators. We also demonstrate that the energy can be extracted from the cavity
      with a similar process.

PMID- 14587792
TI  - Efficient sum-frequency generation of continuous-wave single-frequency coherent
      light at 252 nm with dual wavelength enhancement.
AB  - Highly efficient frequency conversions were conducted to obtain deep-ultraviolet
      single-mode coherent light by use of two-stage external cavities. A power of 154
      mW at approximately 252 nm was obtained with a conversion efficiency of more than
      8% by doubly resonant sum-frequency mixing of 373-nm light from the first-stage
      conversion and 780-nm light from a single-mode Ti:sapphire laser. The output
      performance of the deep-ultraviolet light source is sufficient for use in the
      laser cooling of neutral silicon atoms.

PMID- 14587793
TI  - Sidelobe suppression in volume holographic optical correlators by use of speckle
      modulation.
AB  - By use of speckle modulation on the object beam of a volume holographic optical
      correlation system, we show that the sidelobes of the correlation patterns along
      the vertical direction, as well as those along the horizontal direction, are well
      suppressed. A theoretical explanation and experimental results are presented and
      discussed.

PMID- 14587794
TI  - Infrared holographic recording in lithium tantalate crystals by means of the
      pyroelectric effect.
AB  - Infrared holographic recording in a two-step process is demonstrated in
      stoichiometric iron-doped lithium tantalate crystals. Through absorption of two
      intersecting infrared pulses (A = 1064 nm) a temperature grating and thus a
      modulated pyroelectric field build up. Free electrons, excited by homogeneous
      light of a shorter wavelength (lambda = 532 nm) drift in this field, and a phase
      hologram is stored that can be read nondestructively. The change in refractive
      index depends mainly on the absorption coefficient at the wavelength of the
      recording light and on the intensity of the infrared light. The proposed method
      may be extended to telecommunication wavelengths by choice of suitable dopants.

PMID- 14587795
TI  - Systematic design of single-mode coupled-resonator optical waveguides in photonic
      crystals.
AB  - By establishing a direct relation between the dispersion and the field profile of
      a coupled-resonator optical waveguide (CROW) and those of its constituent
      cavities, we present a systematic method for the design of a single-mode CROW and
      for control of its dispersion. The procedure includes the design of a single-mode
      cavity and control of its frequency by engineering its structure. Then, by
      chaining these cavities in the proper direction and at an appropriate distance,
      we achieve the desired dispersion for the CROW.

PMID- 14587796
TI  - High-speed wavelength-swept semiconductor laser with a polygon-scanner-based
      wavelength filter.
AB  - Ultrahigh-speed tuning of an extended-cavity semiconductor laser is demonstrated.
      The laser resonator comprises a unidirectional fiber-optic ring, a semiconductor
      optical amplifier as the gain medium, and a novel scanning filter based on a
      polygonal scanner. Variable tuning rates up to 1150 nm/ms (15.7-kHz repetition
      frequency) are demonstrated over a 70-nm wavelength span centered at 1.32 microm.
      This tuning rate is more than an order of magnitude faster than previously
      demonstrated and is facilitated in part by self-frequency shifting in the
      semiconductor optical amplifier. The instantaneous linewidth of the source is
      <0.1 nm for 9-mW cw output power and a low spontaneous-emission background of -80
      dB.

PMID- 14587797
TI  - High-average-power femtosecond fiber chirped-pulse amplification system.
AB  - Efficient generation of 76-W average power of 400-fs pulses at 75-MHz repetition
      rate by use of a diode-pumped ytterbium-doped double-clad fiber-based chirped
      pulse amplification system is demonstrated. The key element in the system is a
      diffraction grating compressor consisting of highly efficient transmission
      gratings in fused silica, allowing recompression at this high power level.

PMID- 14587798
TI  - Generation of 3.8-fs pulses from adaptive compression of a cascaded hollow fiber
      supercontinuum.
AB  - We demonstrate generation of 3.8-fs pulses with energies of up to 15 microJ from
      a supercontinuum produced in two cascaded hollow fibers. Ultrabroadband
      dispersion compensation was achieved through a closed-loop combination of a
      spatial light modulator for adaptive pulse compression and spectral-phase
      interferometry for direct electric-field reconstruction (SPIDER) measurements as
      feedback signal.

PMID- 14587799
TI  - Accurate Jones matrix expansion for all orders of polarization mode dispersion.
AB  - I present a simple method for extracting the dispersive elements from a general
      unitary Jones matrix in such a way that the parts comprising the phase delays and
      higher-order dispersion in the two principal states of polarization are separated
      from those describing the frequency-dependent coupling between them. I then
      rigorously expand these two parts into power series in relative optical
      frequency, wherein the coefficients are explicit functions of the polarization
      mode dispersion vectors of various orders. This accurate expansion of the Jones
      matrix reveals in particular the amplitudes and phases of the cross-coupled
      components of the principal states of polarization, which are incorrectly
      described in most polarization mode dispersion models.

PMID- 14587800
TI  - Spatial laser-wing suppression in saturated laser-induced fluorescence without
      spatial selection.
AB  - Spatial wings of laser beams are of great concern in saturated laser-induced
      fluorescence. Their contribution to fluorescence is customarily avoided by
      resolution of laser peaks in the interaction volume. An alternative and versatile
      approach is formulated, based on the derivative of fluorescence with respect to
      laser intensity. It turns out that wing-free data are possible, although they are
      obtained from wing-dependent fluorescence. The advantages of this approach are
      exact centerline detection and simplicity of the experimental setup and
      procedure.

PMID- 14587801
TI  - 20-nm resolution x-ray microscopy demonstrated by use of multilayer test
      structures [corrected].
AB  - A spatial resolution of 20 nm is demonstrated at 2.07-nm wavelength by use of a
      soft x-ray microscope based on Fresnel zone plate lenses and partially coherent
      illumination. Nanostructural test patterns, formed by sputtered multilayer
      coatings and transmission electron microscopy thinning techniques, provide clear
      experimental results.

PMID- 14587802
TI  - Brillouin scattering spectrum in photonic crystal fiber with a partially
      germanium-doped core.
AB  - The Brillouin scattering spectrum in a photonic crystal fiber (PCF) with a
      partially Ge-doped core is measured with a pump-probe technique at a wavelength
      of 1320 nm. One main peak and four subpeaks are observed. The main peak has a
      Lorentzian shape with the bandwidth deltanuB = 66 MHz. Its intensity is six times
      higher than that from a standard single-mode fiber measured under the same
      conditions, which is consistent with the ratio of (1/Aeff(PCF))/(1/Aeff(SMF)),
      where Aeff is the effective area of the fibers. The temperature coefficient for
      the main peak is 0.96 MHz/degrees C. We believe that the subpeaks are caused by
      an interaction between light-wave and guided modes of longitudinal acoustic waves
      in the graded-Ge-doped region, the silica region, and the microstructured
      cladding. An analysis of the guiding and antiguiding properties of the PCF for
      acoustic waves is presented.

PMID- 14587803
TI  - Highly photosensitive Sb/Er/Ge-codoped silica fiber for writing fiber Bragg
      gratings with strong high-temperature sustainability.
AB  - A highly photosensitive Sb/Er/Ge-codoped silica fiber for fabricating fiber Bragg
      gratings (FBGs) with strong high-temperature sustainability is presented. The
      photosensitivity and the high-temperature sustainability of FBGs created in this
      fiber are examined and compared with those produced in a Sn-doped silica fiber.
      The results show that the Sb/Er/Ge fiber has a much higher level of
      photosensitivity than the Sn-doped silica fiber and that the FBGs have a similar
      high-temperature sustainability of 800 degrees C. The strong fluorescence
      properties observed from this fiber are also examined.

PMID- 14587804
TI  - Properties of polarization evolution in spun fibers.
AB  - We study the properties of polarization evolution in sinusoidally spun fibers. It
      is found that, similar to linear birefringent fibers, the evolution of the state
      of polarization exhibits periodicity, which can be measured by distributed
      measurement, such as those made with a polarization optical time domain
      reflectometer. The spatial period is linked with the spin parameters and fiber
      beat length in a simple equation. In combination with a previous finding, it is
      shown that the spatial period is uniquely related to spun-fiber polarization mode
      dispersion. This suggests that distributed fiber polarization mode dispersion can
      be determined throughthe measurement of the spatial period obtained in a
      distributed measurement.

PMID- 14587805
TI  - Design of a highly nonlinear dispersion-shifted fiber with a small effective area
      by use of the beam propagation method with the Gaussian approximation method.
AB  - A new design of a highly nonlinear dispersion-shifted fiber (HNDSF) with an
      effective area of 9.3 microm2 is presented. The three-dimensional beam
      propagation method combined with the Gaussian approximation method is used to
      analyze the new HNDSF. This innovative HNDSF has a unique triple-cladding
      structure that can offer not only a large nonlinear coefficient but also low
      attenuation, low splicing, and bending losses. It is a suitable candidate to
      implement an all-fiber wavelength converter by four-wave mixing.

PMID- 14587806
TI  - Voltage-controllable wavelength-selective optical switching based on multiply
      cascaded long-period fiber gratings.
AB  - A novel wavelength-selective optical switching device based on multiply cascaded
      long-period fiber gratings is proposed and experimentally demonstrated. The on
      and off states of each channel in the optical switching device can be effectively
      switched by voltage-controllable coil heaters. The device has advantages of
      multichannel operation, multiwavelength selectivity, and bandwidth
      controllability. It can be useful for applications in multiwavelength operational
      signal gating, optical switching devices, routers, and multiplexers in optical
      communication systems.

PMID- 14587807
TI  - Distributed three-dimensional fiber Bragg grating refractometer for biochemical
      sensing.
AB  - We demonstrate a three-dimensional (3-D) distributed refractometer that measures
      refractive index in a small volume. The sensor is based on an evanescent-wave
      fiber Bragg grating that is interrogated by low-coherence spectral
      interferometry. The measurement can be performed on a short time scale without
      the need for a mechanical scan. The new sensor was used to simultaneously measure
      glucose concentration in several droplets along a single sensor and to
      interrogate the time-dependent evaporation process of a water droplet. The new
      measurement technique might enable novel 3-D distributed sensors to be developed
      and multiple discrete measurements to be made in a small volume.

PMID- 14587808
TI  - High-speed data encryption over 25 km of fiber by two-mode coherent-state quantum
      cryptography.
AB  - We demonstrate high-speed (250 Mbps) data encryption over 25 km of
      telecommunication fiber by use of coherent states. For the parameter values used
      in the experiment, the demonstration is secure against individual ciphertext-only
      eavesdropping attacks near the transmitter with ideal detection equipment.
      Whereas other quantum-cryptographic schemes require the use of fragile quantum
      states and ultrasensitive detection equipment, our protocol is loss tolerant,
      uses off-the-shelf components, and is optically amplifiable.

PMID- 14587809
TI  - Experimental test of dense wavelength-division multiplexing using novel, periodic
      group-delay-complemented dispersion compensation and dispersion-managed solitons.
AB  - In an all-Raman amplified, recirculating loop containing 100-km spans, we have
      tested dense wavelength-division multiplexing at 10 Gbits/s per channel, using
      dispersion-managed solitons and a novel, periodic-group-delay-complemented
      dispersion-compensation scheme that greatly reduces the timing jitter from
      interchannel collisions. The achieved working distances are approximately 9000
      and approximately 20,000 km for uncorrected bit error rates of <10(-8) and <10(
      3), respectively, the latter corresponding to the use of "enhanced" forward error
      correction; significantly, these distances are very close to those achievable in
      single-channel transmission in the same system.

PMID- 14587810
TI  - Quantitative spectrally resolved imaging through a spectrograph.
AB  - A grating spectrograph can be used for spectrally selective two-dimensional
      imaging if it is operated with a broad entrance slit. The resulting intensity
      distribution in its exit plane is a one-dimensional convolution of the spatial
      and spectral distributions of incident light. We present a dedicated
      deconvolution filter to reconstruct the spatial image from the spectrograph
      output. The algorithm is illustrated on Raman imaging of an underexpanded dry air
      jet. Recorded Raman images correspond to density maps convolved with the Raman
      spectrum of air; the latter essentially acts as a blurring function for the
      density map. The deconvolution filter combines the individual images recorded in
      the O2 and N2 Raman bands into a single image of relative air density.

PMID- 14587811
TI  - Inverse scattering problem for optical coherence tomography.
AB  - We deal with the imaging problem of determining the internal structure of a body
      from backscattered laser light and low-coherence interferometry. Specifically,
      using the interference fringes that result when the backscattering of low
      coherence light is made to interfere with the reference beam, we obtain maps
      detailing the values of the refractive index within the sample. Our approach
      accounts fully for the statistical nature of the coherence phenomenon; the
      numerical experiments that we present, which show image reconstructions of high
      quality, were obtained under noise floors exceeding those present for various
      experimental setups reported in the literature.

PMID- 14587812
TI  - Carbonyl sulfide detection with a thermoelectrically cooled midinfrared quantum
      cascade laser.
AB  - A compact absorption spectrometer with a midinfrared tunable quantum cascade
      laser operating at 4.86 microm (2054 cm(-1)) is used to measure lower
      concentrations of carbonyl sulfide (COS) in air. A detection sensitivity of
      approximately 30 parts in 10(9) of COS and the selectivity of two stable
      isotopes, 12C(16)O32S and 12C(16)O34S, are demonstrated. Specifically, the
      feasibility of detecting COS in expired human breath as a potential noninvasive
      medical diagnostic tool is investigated.

PMID- 14587813
TI  - Lifetime measurement of the 9s level of atomic francium.
AB  - We use two-photon resonant excitation and time-correlated single-photon counting
      techniques on a sample of 210Fr atoms confined and cooled in a magneto-optical
      trap to measure the lifetime of the 9s excited level. Direct measurement of the
      decay through the 7P(3/2) level at 851 nm yields a lifetime of 107.53 +/- 0.80
      ns.

PMID- 14587814
TI  - Laser terahertz-emission microscope for inspecting electrical faults in
      integrated circuits.
AB  - A laser terahertz-emission microscope (LTEM) system is proposed and developed for
      inspecting electrical faults in integrated circuits (IC). We test a commercial
      operational amplifier while the system is operating. Two-dimensional terahertz
      emission images of the IC chip are clearly observed while the chip is scanned
      with a femtosecond laser. When one of the interconnection lines is cut, the
      damaged chip has a LTEM image different from that of normal chips. The results
      indicate that the LTEM system is a potential tool for IC inspection.

PMID- 14587815
TI  - Volumetric diffuse optical tomography of brain activity.
AB  - We present three-dimensional diffuse optical tomography of the hemodynamic
      response to somatosensory stimulation in a rat. These images show the feasibility
      of volumetrically imaging the functional response to brain activity with diffuse
      light. A combination of positional optode calibration and contrast-to-noise ratio
      weighting was found to improve imaging performance.

PMID- 14587816
TI  - High-resolution optical coherence microscopy for high-speed, in vivo cellular
      imaging.
AB  - Optical coherence microscopy (OCM) is demonstrated with a high-speed, broadband,
      reflective-grating phase modulator and a femtosecond Ti:Al2O3 laser. The novel
      system design permits high-resolution OCM imaging in a new operating regime in
      which a short coherence gate is used to relax the requirement for high-numerical
      aperture confocal axial sectioning. In vivo cellular imaging is demonstrated in
      the Xenopus laevis tadpole and in human skin with a 3-microm coherence gate and a
      30-microm confocal gate. The ability to achieve cellular imaging with a lower
      numerical aperture should facilitate the development of miniaturized probes for
      in vivo imaging applications.

PMID- 14587817
TI  - Improved signal-to-noise ratio in spectral-domain compared with time-domain
      optical coherence tomography.
AB  - A signal-to-noise ratio (SNR) analysis is presented for optical coherence
      tomography (OCT) signals in which time-domain performance is compared with that
      of the spectral domain. A significant SNR gain of several hundredfold is found
      for acquisition in the spectral domain. The SNR benefit is demonstrated
      experimentally in a hybrid time-domain-spectral-domain OCT system.

PMID- 14587818
TI  - Metabolism-enhanced tumor localization by fluorescence imaging: in vivo animal
      studies.
AB  - We present a high-sensitivity near-infrared optical imaging system for
      noninvasive cancer detection and localization based on molecularly labeled
      fluorescent contrast agents. This frequency-domain system utilizes the
      interferencelike pattern of diffuse photon density waves to achieve high
      detection sensitivity and localization accuracy for the fluorescent heterogeneity
      embedded inside the scattering media. A two-dimensional localization map is
      obtained through reflectance probe geometry and goniometric reconstruction. In
      vivo measurements with a tumor-bearing mouse model by use of the novel Cypate
      mono-2-deoxy-glucose fluorescent contrast agent, which targets the enhanced tumor
      glycolysis, demonstrate the feasibility of detection of a 2-cm-deep subsurface
      tumor in the tissuelike medium, with a localization accuracy within 2-3 mm.

PMID- 14587819
TI  - Combined Raman and continuous-wave-excited two-photon fluorescence cell imaging.
AB  - We demonstrate a confocal optical microscope that combines cw two-photon-excited
      fluorescence microscopy with confocal Raman microscopy. With this microscope fast
      image acquisition with fluorescence imaging can be used to select areas of
      interest for subsequent chemical analysis with spontaneous Raman imaging. The
      distribution of the UV-absorbing fluorophore Hoechst 33342 in the apoptotic HeLa
      cells is measured in the combined cw two-photon-excited fluorescence and Raman
      microscopy modes. The 647-nm line of a Kr-ion laser is used to excite both the
      Raman scattering and the two-photon-excited fluorescence emission. The lateral
      and axial resolutions in the two imaging modes are compared by use of the
      Gaussian beam approximation and backprojection of the focal volume through the
      confocal pinhole.

PMID- 14587820
TI  - Enhanced sensitivity and spatial resolution for in vivo imaging with low-level
      light-emitting probes by use of biocompatible chemical agents.
AB  - We describe a technique that uses biocompatible chemical agents to enhance both
      the sensitivity and the resolution of in vivo imaging with low-level light
      emitting probes. We demonstrate experimentally, with chemiluminescence (CL)
      imaging in vitro as an example, that the detected intensity of CL from treated 3
      mm-thick skin tissue is approximately fivefold stronger than that from untreated
      skin. The spatial resolution correspondingly increases approximately threefold.

PMID- 14587821
TI  - Engineering transverse Bragg resonance waveguides for large modal volume lasers.
AB  - We recently analyzed a new class of laser amplifier based on transverse Bragg
      reflection. We show that the unique properties of Bragg confinement make it
      possible through modal loss discrimination to achieve single-transverse-mode
      operation with transverse modal size that is an order of magnitude larger than in
      lasers that depend on total internal reflection for transverse confinement.

PMID- 14587822
TI  - Erbium-doped fiber laser simultaneously mode locked on more than 24 wavelengths
      at room temperature.
AB  - We demonstrate simultaneous mode locking of more than 24 wavelengths at 3 GHz in
      an actively mode-locked erbium-doped fiber laser operating at room temperature.
      The multiwavelength operation is achieved when a frequency shifter and an all
      fiber 50-GHz periodic filter are inserted into a ring cavity. Active mode locking
      is performed with an amplitude modulator, and pulses with a FWHM of 30 ps are
      obtained.

PMID- 14587823
TI  - Sub-100-ps amplitude-modulation mode-locked Tm-Ho:BaY2F8 laser at 2.06 microm.
AB  - We report the generation of sub-100-ps pulse trains near the 2.06-microm
      wavelength in an actively mode-locked diode-pumped Tm-Ho:BaYF laser operating at
      room temperature. Transform-limited, 97-ps Gaussian pulses at a 100-MHz
      repetition rate with an average power in excess of 20 mW and with a carrier
      wavelength tunable by approximately 50 nm near 2.066 microm are demonstrated.

PMID- 14587824
TI  - Tunable solid-state lasers incorporating dye-doped, polymer-nanoparticle gain
      media.
AB  - Tunable laser action in the visible spectrum has been established for what is
      believed to be the first time by use of dye-doped, polymer-silica nanoparticle
      gain media. The silica nanoparticles, ranging from 9 to 12 nm in diameter, appear
      to be uniformly dispersed in the poly(methyl methacrylate) matrix because the
      optical homogeneity of the gain medium is maintained. With Rhodamine 6G dye and
      30% weight-by-weight silica nanoparticles, laser action was established in the
      567-603-nm range. At the peak wavelength (lambda approximately 580 nm), laser
      conversion efficiency is approximately 63% at a beam divergence of 1.9 mrad
      (approximately 1.3 times the diffraction limit). The new solid-state gain medium
      also exhibits a reduction in /deltan/deltaT/.

PMID- 14587825
TI  - Efficient frequency doubling of a vertical-extended-cavity surface-emitting laser
      diode by use of a periodically poled KTP crystal.
AB  - Blue light with a cw power in excess of 42 mW is generated from a frequency
      doubled, extended-cavity InGaAs/GaAs 980-nm surface-emitting laser by use of a
      periodically poled KTP crystal.

PMID- 14587826
TI  - Fundamental and vortex solitons in a two-dimensional optical lattice.
AB  - Fundamental and vortex solitons in a two-dimensional optically induced waveguide
      array are reported. In the strong localization regime the fundamental soliton is
      largely confined to one lattice site, whereas the vortex state comprises four
      fundamental modes superimposed in a square configuration with a phase structure
      that is topologically equivalent to the conventional vortex. However, in the weak
      localization regime, both the fundamental and the vortex solitons spread over
      many lattice sites. We further show that fundamental and the vortex solitons are
      stable against small perturbations in the strong localization regime.

PMID- 14587827
TI  - Non-Gaussian statistics of an optical soliton in the presence of amplified
      spontaneous emission.
AB  - We apply an approach based on the Fokker-Planck equation to study the statistics
      of optical soliton parameters in the presence of additive noise. This rigorous
      method not only allows us to reproduce and justify the classical Gordon-Haus
      formula but also leads to new exact results.

PMID- 14587828
TI  - Stabilization of intracavity frequency-doubled lasers with type I phase matching.
AB  - We report a new method for stabilizing the power of intracavity frequency-doubled
      multimode lasers with type I phase matching. Such lasers usually show strong
      fluctuations of the output power caused by coupling of longitudinal laser modes
      in the nonlinear crystal. We eliminate these fluctuations by placing the gain
      medium and nonlinear crystal in specific locations in the laser cavity where the
      nonlinear coupling of different longitudinal modes is strongly reduced.

PMID- 14587829
TI  - Quadratic soliton self-reflection at a quadratically nonlinear interface.
AB  - The reflection of bulk quadratic solutions incident onto a quadratically
      nonlinear interface in periodically poled potassium titanyl phosphate was
      observed. The interface consisted of the boundary between two quasi-phase-matched
      regions displaced from each other by a half-period. At high intensities and small
      angles of incidence the soliton is reflected.

PMID- 14587830
TI  - TEM00 terawatt amplification by use of micro-optic spatial mode conversion.
AB  - Micro-optic technology is used in a terawatt multipass Ti:sapphire amplifier to
      convert high-multimode, 532-nm radiation from an unstable resonator Nd:YAG laser
      into a TEM00 amplified output without sacrificing the amplifier-to-pump energy
      conversion efficiency. Experimental measurements and Fourier analysis of the
      spatial mode show a 3.8-fold increase in the peak irradiance and an order-of
      magnitude improvement in the spatial contrast.

PMID- 14587831
TI  - Mode conversion and birefringence adjustment by focused-ion-beam etching for
      slanted rib waveguide walls.
AB  - We describe how focused-ion-beam (FIB) etching of slanted rib waveguide walls can
      be used to modify the differential group delay in a waveguide and introduce TE to
      TM mode conversion in a silicon-on-insulator rib waveguide. We achieved mode
      conversion by modifying the geometric cross section of a single-mode rib by FIB
      trimming. Waveguides with different lengths of 45 degrees slant angle rib
      waveguide walls were fabricated and characterized. We measured the differential
      group delays and the mode conversion achieved for waveguides with different
      lengths of a FIB-trimmed slanted rib wall.

PMID- 14587832
TI  - Low-coherence tandem interferometer for measurement of group refractive index
      without knowledge of the thickness of the test sample.
AB  - A new low-coherence interferometric technique is proposed for measuring the group
      refractive indices of dispersive samples with high accuracy. A tandem
      configuration of interferometers is used to compensate for the asymmetrical
      distortion of interferograms that results from the broad spectrum of the light
      source. The group refractive index can be measured without knowledge of the
      geometrical thickness of the sample under test. The proposed technique can
      successfully measure even a thick sample. Computer calculations have shown the
      effectiveness of the proposed technique, which was verified by preliminary
      experiments; the difference between the experimental result and the catalog data
      was 7 x 10(-4).

PMID- 14587833
TI  - Electro-optic Solc-type wavelength filter in periodically poled lithium niobate.
AB  - We demonstrate an electro-optic Solc-type wavelength filter in periodically poled
      lithium niobate (PPLN). A Solc-type transmission spectrum is observed
      experimentally in PPLN with four periods from 20.2 to 20.8 microm. Modulation of
      the transmission power of the filter is realized by application of electric
      fields along the Y axis of the PPLN. It is observed that the wavelength can also
      be tuned by temperature.

PMID- 14587834
TI  - 12-fs pulses from a continuous-wave-pumped 200-nJ Ti:sapphire amplifier at a
      variable repetition rate as high as 4 MHz.
AB  - We demonstrate a novel compact femtosecond Ti:sapphire laser system operating at
      repetition rates from 10 kHz to 4 MHz. The scheme is based on the combination of
      a broadband cavity-dumped oscillator and a double-pass Ti:sapphire amplifier
      pumped by a low-noise cw solid-state laser. Amplified pulses with an extremely
      smooth spectrum, a duration of only 12 fs, and less than 0.25% rms fluctuation
      are generated in a beam with M2 < 1.2. A maximum pulse energy of 210 nJ and an
      average output power of as much as 720 mW are achieved. This output energy is
      sufficient to generate a stable continuum in a sapphire disk.

PMID- 14587835
TI  - 30-mJ, diode-pumped, chirped-pulse Yb:YLF regenerative amplifier.
AB  - A diode-pumped chirped-pulse regenerative amplifier with a cooled Yb:YLF crystal
      has been developed. The output pulse energy is 30 mJ at 20-Hz repetition rate. A
      high effective extraction efficiency of 68% is obtained, which is attributed to
      reduced saturation fluence at low temperature and to a high effective pulse
      energy fluence during regenerative amplification. After pulse compression by use
      of a parallel grating pair, 18-mJ pulse energy and 795-fs pulse duration are
      obtained.

PMID- 14587836
TI  - Deadly waters run deep: the global arsenic crisis.

PMID- 14587837
TI  - Environmental risk assessment of metals for international chemicals safety
      programs: a recent and fast growing area of regulatory development, requiring new
      science concepts.

PMID- 14587838
TI  - Sampling gaseous oxidation products of aromatic compounds in gas/particle
      separation systems.
AB  - In this study we performed a direct comparison between two different ambient air
      samplers to characterize their performance in sampling oxidized gaseous organic
      compounds, known as oxidation products of aromatics. We investigated compounds
      with a variety of functional groups and vapor pressures. A polyurethane foam
      (PUF) adsorbent and an annular diffusion denuder sampler were operated along with
      particle filters. In both systems the sampling devices were liquid-extracted,
      followed by derivatization and analysis by GC-MS. The PUF system works very well
      for aromatic as well as non-aromatic compounds, whereas the denuder shows smaller
      collection efficiencies for highly volatile non-aromatic compounds. In addition,
      the sampling efficiencies in the PUF set-up are in good agreement with the
      calculated vapor pressures of the compounds and also the particle phase is not
      affected by most compounds.

PMID- 14587839
TI  - Sampling and analysis considerations for the determination of hexavalent chromium
      in workplace air.
AB  - Airborne hexavalent chromium (Cr[VI]) is a known human respiratory carcinogen and
      allergen. Workers in a variety of industries may be exposed to airborne
      hexavalent chromium, with exposures frequently occurring via inhalation and/or
      dermal contact. Analytical methods for the measurement of Cr(VI) compounds in
      workplace samples, rather than for the determination of total elemental chromium
      in workplace air, are often desired because exposure limit values for Cr(VI)
      compounds are much lower than for total Cr. For years, sampling and analytical
      test methods for airborne Cr(VI) have been investigated so as to provide means
      for occupational exposure assessment to this highly toxic species. Inter
      conversion of trivalent chromium (Cr[III]) and Cr(VI) can sometimes occur during
      sampling and sample preparation, and efforts to minimize unwanted redox reactions
      involving these chromium valences have been sought. Because of differences in
      toxicity, there is also interest in the ability to differentiate between water
      soluble and insoluble forms of Cr(VI), and procedures that provide solubility
      information concerning Cr(VI) compounds have been developed. This paper reviews
      the state of the art concerning the measurement of airborne Cr(VI) compounds in
      workplace aerosols and related samples.

PMID- 14587840
TI  - Thiram: degradation, applications and analytical methods.
AB  - In this review a brief introduction to thiram (tetramethylthiuram disulfide;
      TMTD) pesticide has been given along with other applications. All the important
      methods available are systematically arranged and are listed under various
      techniques. Some of these methods have been applied for the determination of
      thiram in commercial formulations, synthetic mixtures in grains, vegetables and
      fruits. A comparison of different methods is the salient feature of this review.

PMID- 14587841
TI  - Selective extraction of persistent organic pollutants from environmental
      matrices.
AB  - An attempt is made to determine the bioavailability of persistent organic
      pollutants (POP's) in environmental matrices. The approach is based on the use of
      the Hildebrand Solubility Parameter, and its individual parameters of hydrogen
      bonding, dispersion and polarity to select weak and strong solvents to extract
      POP's from soil matrices. The approach has been applied to both spiked soils and
      certified reference materials. Initial results indicate that it is possible to
      fractionate POP's from soil matrices based on their ability to be extracted from
      soil by particular solvents.

PMID- 14587842
TI  - Evaluation of diffusive samplers and photoionisation detectors for measuring very
      short peak exposures in the workplace.
AB  - The extent to which very short peak widths, peak frequency, sampling time and
      post-sampling/pre-capping time impact upon occupational exposure measurements of
      toluene has been investigated using diffusive tubes. Additionally, the effect of
      the width of the peak on the estimation of peak maximum concentration and time
      weighted average (TWA) concentration from real-time instruments (photoionisation
      detectors-PIDs) was also studied, and their responses modelled. No clear
      differences were perceived between diffusive and pumped tube results. Mean biases
      of -5 to +6% were recorded but no trend could be distinguished with respect to
      any of the variables examined; the main source of uncertainty was attributed to
      analytical uncertainty. The diffusive tubes can therefore be used to measure
      short term transient toluene concentrations (e.g. 5 s duration) over short (15
      min) exposure periods. The two slower responding PIDs (t50 = 4 s) underestimated
      the maximum concentration of short term peaks having durations less than 10 s.
      The other three PIDs (t50 < or = 2 s) only significantly underestimated the
      maximum concentration of short term peaks having durations of 2 s and below.
      Pulse duration appeared to affect the PID's estimation of peak height more than
      peak area (TWA concentration).

PMID- 14587844
TI  - The determination of air/water partition coefficients for alkyl carboxylic acids
      by a new indirect method.
AB  - The air/water partition coefficients of carboxylic acids, Kw, especially those of
      high molecular weight, are very difficult to determine directly. Values of Kw can
      be obtained by an indirect method as Kw = K/P where K is an air/solvent partition
      coefficient and P is the corresponding water/solvent partition coefficient. In
      the present method, gas-liquid chromatographic data and water/solvent partition
      data are used to obtain 'descriptors' of carboxylic acids that can then be used
      to determine the required K, P, and thus Kw values. These are reported for all
      the 24 n-alkyl carboxylic acids from formic acid to n-tetracosanoic acid, and for
      seven branched chain alkyl carboxylic acids. There is good agreement with
      literature values of Kw, where available, although the present data on the n
      alkyl carboxylic acids is much more self consistent than the literature data.

PMID- 14587843
TI  - Air concentrations and urinary metabolites of polycyclic aromatic hydrocarbons
      among paving and remixing workers.
AB  - The exposure of paving workers to polycyclic aromatic hydrocarbons (PAH) during
      stone mastic asphalt (SMA) paving and remixing was evaluated. The effects on the
      workers' PAH exposure were also evaluated during the use of an industrial by
      product, coal fly ash (CFA), instead of limestone as the filler in the SMA. The
      PAH exposure was measured by personal air sampling and by analysing the levels of
      urinary naphthols, phenanthrols and 1-hydroxypyrene (1-OHP) in the workers' pre-
      and post-shift urine samples. The respiratory PAH exposure of the paving workers
      (geometric mean (GM) 5.7 microg m(-3)) was about ten-fold that of the traffic
      controllers (GM 0.43 microg m(-3)). The levels of PAH metabolites were
      significantly higher (p < 0.05) in the post-shift urine samples than in the pre
      shift urine samples, and the levels of metabolites in the post-shift urine of
      paving workers were significantly higher than in that of the controls (p < 0.01).
      Urinary 1-naphthol correlated well with the airborne concentrations of the two-
      to three-ring PAHs (r = 0.544, p = 0.003) and naphthalene (r = 0.655, p < 0.001),
      when non-smoking paving workers were tested. A good correlation was observed
      between urinary 1-OHP and the airborne concentrations of the four- to six-ring
      PAHs (r = 0.524, p = 0.003) as well as total PAHs (r = 0.575, p = 0.001). The
      concentrations of 1-OHP and phenanthrols in the urine of the pavers were
      significantly higher (p < 0.01) during remixing than during SMA paving. The CFA
      in the asphalt had no effect on the airborne PAH exposure or on the
      concentrations of the PAH metabolites in the paving workers' urine.

PMID- 14587845
TI  - Concentrations of perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid
      (PFOA) in vacuum cleaner dust collected in Japanese homes.
AB  - Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are shown to
      be globally distributed, environmentally persistent and bioaccumulative. Although
      there is evidence that these compounds exist in the serum of non-occupationally
      exposed humans, the pathways leading to the presence of PFOS and PFOA are not
      well characterized. The concentrations of PFOS and PFOA in the vacuum cleaner
      dust collected in Japanese homes were measured. The compounds were detected in
      all the dust samples and the ranges were 11-2500 ng g(-1) for PFOS and 69-3700 ng
      g(-1) for PFOA. It was ascertained that PFOS and PFOA were present in the dust in
      homes, and that the absorption of the dust could be one of the exposure pathways
      of the PFOS and PFOA to humans. With regard to risk management, it is important
      to consider the usage of PFOS and PFOA in the indoor environment in order to
      avoid further pollution.

PMID- 14587846
TI  - Development of a sampling train for arsenic in pyrolysis vapours resulting from
      pyrolysis of arsenic containing wood waste.
AB  - In the present study a sampling and analysis method for arsenic emissions during
      pyrolysis of arsenic containing wood, such as chromated copper arsenate (CCA)
      treated wood, has been developed. The procedure is based on the NIOSH (National
      Institute for Occupational Safety and Health) standard for arsenic trioxide
      sampling. Validation for this specific application is needed since pyrolysis of
      arsenic containing wood leads to a gas stream containing sticky tar compounds and
      aerosols. Validation was carried out through tube furnace experiments using both
      CCA treated wood and arsenic trioxide powder as input. The outlet of the tube
      furnace was coupled to a cooling section and sampling train. The sampling train
      consisted of one or more filter sections and impingers. Different combinations of
      filters (untreated or impregnated) and impingers, as well as different
      combinations of washing solutions were tested. The different units of the
      sampling train were analysed by inductively coupled plasma mass spectrometry (ICP
      MS) in order to determine the distribution of arsenic over the different units.
      For the working conditions considered (pyrolysis at 350 degrees C for 20 minutes
      with a nitrogen flow rate of 100 Nl h(-1)) the combination of a quartz cooling
      tube and a cellulose ester membrane filter impregnated with a Na2CO3-glycerol
      solution was sufficient to capture the arsenic. Two extra impingers (the first
      one containing 50 ml HNO3 1 M in the case of CCA treated wood and 50 ml NaOH 0.1
      M in the case of As2O3 and the second one containing 50 ml NaOH 0.1 M) were added
      downstream of the filter section as backup either in case of filter failure or to
      check whether all the arsenic released is captured by the cooling tube and
      filter.

PMID- 14587847
TI  - The effects of anthropogenic particulate emissions on roadway dust and Nerium
      oleander leaves in Messina (Sicily, Italy).
AB  - Complementary studies on the inorganic chemical composition of Nerium oleander
      leaves collected in the town of Messina (Sicily, Italy) and seven grain-size
      fractions of local roadway dust have been carried out. Data and maps are
      presented to show that the particulate matter present in the air of Messina
      contains trace elements significantly in excess with respect to the average
      continental earth crust. The anomalies follow the outline of the urban area, the
      highest concentrations of trace elements being observed where traffic density is
      highest. Chemical and isotopic analyses of both road dust and Nerium oleander
      leaves indicate that Pb contamination still characterizes roads with heavy
      traffic. In addition to Pb, other metals such as Pt, Pd, Sb, Au, Br, Zn, Cu, Mo,
      and Cd are significantly enriched in roadway dust, indicating their common
      anthropogenic origin, especially from traffic. SEM/EDS study of some roadway dust
      particles has shown the presence of gypsum probably of secondary origin, mixed
      particles formed by coagulation or gas-to-particle conversion, and porous
      spherical particles apparently emanating from combustion processes.

PMID- 14587848
TI  - Immune response of earthworms (Lumbricus terrestris, Eisenia andrei and
      Aporrectodea tuberculata) following in situ soil exposure to atmospheric
      deposition from a cement factory.
AB  - In order to reduce their energy costs, many cement plants use fuel product
      substitutes (old tyres and used oil). The combustion of these products generates
      a metal increase (e.g. Cu, Cd, Pb and Zn) in the atmospheric emissions. After
      their release, these elements are deposited into the environment and could
      eventually accumulate up to concentrations of concern. At the Saint-Laurent
      cement factory (Joliette, QC, Canada), maximum deposition of these elements
      occurs in the direction of prevailing winds (North-East). We evaluated the
      potential impact of these depositions upon the immune system of three earthworm
      species (Lumbricus terrestris, Eisenia andrei and Aporrectodea tuberculata)
      exposed in a natural environment. The exposure sites were 0.5, 1.0, and 2.0 km
      downwind from the cement factory, along with an upwind reference site. The immune
      parameters studied were the cell viability and phagocytic potential of the immune
      cells (coelomocytes). For both L. terrestris and E. andrei, after 7 d exposure,
      none of the measured parameters showed significant differences among the sites.
      On the other hand, for the indigenous worm A. tuberculata, in the most exposed
      zone (at 0.5 km), we observed an increase in cell viability and phagocytic
      potential. This increase could possibly be attributed to physicochemical effects
      such as the alkaline pH of the soil, or alternatively, it could result from
      beneficial effects induced by an increased calcium supply.

PMID- 14587849
TI  - Application of laser-based ion mobility (IM) spectrometry for the analysis of
      polycyclic aromatic compounds (PAC) and petroleum products in soils.
AB  - The capability of laser-based IM spectrometry to detect PAC and petroleum
      products (oils) in model matrices, laboratory reference (LR) materials and in
      real-world contaminated soil samples was demonstrated. Quantitative IM
      investigations of PAC-doped PVC films yielded detection limits in the ppm range
      for single PAC. The potential of IM spectrometry for in situ analysis was
      demonstrated by the analysis of PAC-containing certified reference (CR) material,
      and of petroleum product-containing LR materials and real-world soil samples. The
      calibration of IM signals obtained from oil-doped LR materials was also possible,
      and detection of oils with concentrations below 100 mg kg(-1) was achieved. The
      in situ analysis of real-world contaminated soils with the IM and LIF techniques
      was in good accordance with ex situ reference investigations.

PMID- 14587850
TI  - Organic contamination in the greenhouse soils from Beijing suburbs, China.
AB  - Selected persistent organic pollutants including HCHs, DDTs and PAHs together
      with PAEs were determined in the greenhouse soils from Beijing suburbs. The total
      concentrations were 11.64-29.80 ng g(-1) for HCHs, 18.04-101.33 ng g(-1) for
      DDTs, 1.34-3.15 microg g(-1) for PAEs and 1.92-7.84 microg g(-1) for PAHs,
      respectively. Predominance of beta-HCH in all samples was obviously observed,
      suggesting a lack of new HCHs sources. High concentrations of DDE and DDD in
      comparison to their parents in the samples indicated that most of the DDT had
      been transformed into its metabolites. The contamination of PAHs was relatively
      serious and the most abundant compounds were 4-, 5- and 6-ring unsubstituted
      PAHs. The profiles reflect the important effect of traffic on the PAHs remaining
      in greenhouse soils. Three phthalate esters (DIBP, DnBP and DEHP) accounted for
      more than 97% of the phthalates studied. Analysis of n-alkanes was also performed
      in order to trace the natural or anthropogenic sources of hydrocarbons.
      Characterization and identification of these compounds in greenhouse soil may
      help in development of strategies to be used in monitoring organic pollutants in
      this region.

PMID- 14587851
TI  - 210Po bioaccumulation by mushrooms from Poland.
AB  - The paper presents results on 210Po activity concentration measured in mushroom
      samples collected in northern Poland (Bialogard and Elblag areas). Among 20
      species of wild mushrooms, King Bolete (Boletus edulis), accumulated 210Po in the
      highest degree. Therefore this species of higher mushrooms is an excellent
      bioindicator for 210Po radioactivity in the land environment. Finally, the
      effective dose of polonium emission was calculated for a consumer of King Bolete.
      Wild mushroom consumption contributed up to 37 microSv to the effective dose in
      an individual consuming about 5 kg (fresh weight) of heavily contaminated Boletus
      edulis species per year.

PMID- 14587852
TI  - Artifact evidence in carbonyl compound sampling using the enclosure technique
      with cuvette system.
AB  - Biogenic hydrocarbon emission rates from individual plant species have been
      estimated experimentally placing small plants or branches in enclosures and
      measuring the emission rates of the compounds. All-Teflon chambers (cuvettes)
      where air samples are drawn through tubes packed with adsorbents, have been
      commonly used for plant enclosure. Sampling of carbonyl compounds emitted from
      plants has been done using 2,4-dinitrophenylhydrazine coated particles and the
      derivative carbonyl compounds have been analyzed by HPLC-UV. In this work, the
      enclosure technique using a cuvette for measurements of carbonyl compound
      emissions from plants was evaluated. Blank measurements in an empty cuvette have
      revealed quite different results for experiments performed under laboratory and
      field conditions. Rigorous univariate statistical analysis of the data obtained
      indicate that the analytical procedure to determine carbonyl compounds at trace
      levels in emission samples using the cuvette may lead to positive artifacts
      during field sampling. This analysis applied to laboratory measurements showed no
      difference in the results for the cuvette and external lines. Multivariate
      statistical calculations point out that solar light intensity accounts for the
      high carbonyl compound levels, especially for acetaldehyde, in the empty cuvette.

PMID- 14587853
TI  - Distribution of mercury in the tissues of five species of freshwater fish from
      Lake Mead, USA.
AB  - Total mercury (Hg) concentrations were determined in seven tissues (skeletal
      muscle, liver, blood, gonad, brain, gill, and heart) of 59 striped bass and four
      tissues (muscle, liver, blood, and gonad) of 69 largemouth bass, 76 channel
      catfish, 12 bluegill, and 22 blue tilapia collected from Lake Mead, USA. Mercury
      levels generally increased according to trophic level and fish length. For
      striped bass, mean Hg levels (ng g(-1), wet mass) were highest in the liver
      (531), followed by muscle (309), heart (186), gonad (136), brain (77), gill (52),
      and blood (36). Similarly, Hg levels in the catfish and tilapia were liver >
      muscle > gonad > blood. In contrast, largemouth bass and bluegill had the highest
      levels in muscle, followed by liver, gonad, and blood. Generally, Hg levels were
      strongly correlated among the tissues, especially for blood/muscle and
      blood/liver. As the body burden of Hg increased, the concentration in blood and
      organs increased relative to the concentration in muscle. The trend was most
      pronounced for the liver. These relationships could form the basis of a
      predictive model and suggest that blood and muscle (plugs) could be useful for a
      non-lethal measure of Hg concentration and exposure in fish. For the striped
      bass, elevated Hg levels in the tissues were also correlated with degree of
      emaciation. Liver-to-muscle ratios were similar to literature values, except for
      tilapia with an average ratio of approximately 1.7, which is higher than
      generally reported for non-piscivores. Finally, this study demonstrates the
      usefulness of a solid sampling approach in trace element monitoring, especially
      as pertaining to in vivo analysis, analysis of a large number of samples and
      reduction of contamination risk.

PMID- 14587854
TI  - High temporal resolution monitoring of inorganic nitrogen load in drainage
      waters.
AB  - Nitrate (NO3-), ammonium (NH4+) and pH were monitored with a novel flow cell
      equipped with ion-selective electrodes (ISEs) in a drainage pipe during one year.
      The high temporal resolution of the measurements (six measurements per hour)
      allowed the detection of diurnal oscillations in pH, NO3- and NH4+
      concentrations, the relation of variations in concentrations to discharge rates
      changing during rain events, understanding of the processes resulting in such
      variations and tracing of unpredictable manure spills. Annual loads estimated
      from random samples collected every second day tended to underestimate the "true"
      loads calculated from quasi-continuous electrode measurements by 550% for NH4+
      and 22% for NO3-.

PMID- 14587855
TI  - Development of an integrative passive sampler for the monitoring of organic water
      pollutants.
AB  - The development of convenient and competitive devices and methods for monitoring
      of organic pollutants in the aquatic environment is of increasing interest. An
      integrative passive sampling system has been developed which consists of a solid
      poly(dimethylsiloxane) (PDMS) material (tube or rod), acting as hydrophobic
      organic receiving phase, enclosed in a water-filled or an air-filled low-density
      polyethylene (LDPE) membrane tubing. These samplers enable the direct analysis of
      the pollutants accumulated during exposure in the receiving phase by
      thermodesorption-GC/MS, avoiding expensive sample preparation and cleanups. The
      capabilities of these sampling devices were studied for the sampling of 20
      persistent organic pollutants (chlorobenzenes, hexachlorocyclohexanes, p,p'-DDE,
      PAHs, and PCBs) in laboratory exposure experiments. For the three sampler designs
      investigated the uptake of all target analytes was integrative over exposure
      periods up to 9 days (except PCB 101). The determined sampling rates range from 4
      to 1340 microl h(-1) for the water-filled samplers and from 20 to 6360 microl h(
      1) for the air-filled ones, respectively. The sampling rate of the analytes is
      dependent on their molecular weight, partition between water and sampler media
      (PDMS, polyethylene, water, air) and also of the sampler design. The passive
      samplers enable the estimation of time-weighted average (TWA) concentration of
      water pollutants in the lower ng l(-1) to pg l(-1) range.

PMID- 14587856
TI  - Pharmaceutical and personal care products in sewage treatment works.
AB  - In this study a number of analytical procedures are described to determine
      pharmaceuticals and personal care products (PPCPs) and their metabolites during
      sewage treatment. The work shows that PPCPs occur in sewage influent and are
      removed by various wastewater treatment processes. PPCPs include a wide range of
      chemicals such as prescription drugs as well as diagnostic agents, fragrances,
      sun-screen agents, and various other compounds commonly present in household
      items (e.g. detergents, cleaners, toothpastes etc.). During this study a number
      of PPCPs including painkillers (aspirin, ibuprofen), cholesterol control
      medication (clofibric acid), antibacterial agents (triclosan), musks (including
      galaxolide and tonalide), X-ray contrast media (diatrizoate), cancer treatment
      drugs (cyclophosphamide) and anti-depressant drugs (fluvoxamine) were
      investigated. Analysis was carried out using a number of techniques. Samples were
      extracted using solid phase extraction or liquid-liquid extraction and the
      extracts analysed using capillary gas chromatography-mass spectrometry (GC-MS)
      with selected ion monitoring or liquid chromatography mass spectrometry (LC-MS)
      or LC-MS-MS. The results obtained show that aspirin, clolibric acid, diatrozate,
      fluvoxamine and cyclophosphamide were not detected in any of the crude sewage or
      sewage effluent samples above the limit of detection of the applied methods.
      Ibuprofen was detected in all crude sewage samples as well as in all effluent
      samples with one exception. Removal of ibuprofen by the different STWs was
      generally between 80-100%, with the exception of one STW where removal was poor
      (14.4 to 44%). Triclosan was also detected in all crude sewage samples and in all
      sewage effluent samples. The highest concentration of triclosan detected was 3100
      ng l(-1). A high removal efficiency was observed in effluent samples taken on two
      occasions (average removal 95.6%). The concentrations of musks detected in the
      crude sewage were generally low except for galaxolide and tonalide. The results
      from STW effluent samples showed significant removal of galaxolide (70-83%
      removal) except at one STW (STW 1) where removal was low (57% and 39%). Similar
      removal efficiencies for tonalide were achieved at these STWs (73-96%) except at
      STW 1 where removal was poor (53%).

PMID- 14587857
TI  - Investigation into the relationship between major and minor element contents and
      particle size and leachability of boron in fly ash from coal fuel thermal power
      plants.
AB  - A basic investigation of boron in discharged fly ash by coal fuel thermal power
      plants in several worldwide locations was carried out. Eight kinds of fly ash
      sample were prepared from eight coal fuel thermal power plants. Two of the fly
      ash samples were used to examine the relationship between the concentration of
      boron in fly ash and the particle size. When the particle size of fly ash is
      smaller, there is a possibility that it will be released into the air and spread
      over a wide area in the environment. However, it has become apparent that fly ash
      of smaller particle size has a higher concentration of boron and a higher
      enrichment factor. In other fly ash samples, the boron contents were examined and
      leaching tests were carried out. There is acidic fly ash as well as alkaline fly
      ash that contains larger amounts of acidic or basic salts. On alkaline fly ash,
      when the concentration of boron bound to Fe-Mn oxide is low; it has become
      apparent that leaching boron is increased in a solution with lower pH of
      approximately 4 which is nearly the pH of acid rain.

PMID- 14587858
TI  - Copper leaching from brake wear debris in standard extraction solutions.
AB  - Quantification of the copper content of and copper leaching from a disc brake
      wear debris sample was performed using microwave-assisted acid digestion, the
      Federal Toxicity Characteristic Leaching Procedure (TCLP), and the State of
      California Waste Extraction Test (WET). The brake wear debris tested was a
      composite sample obtained from a brake dynamometer test of one brake pad source
      material. Comparative digestion studies demonstrated that a modified aqua regia
      matrix (HNO3:HCl:H2O2 = 1:3:0.5) optimized the digestion effectiveness for
      determining the total copper content in the brake wear debris. No significant
      sample heterogeneity within the brake wear debris was observed, based on
      statistically indistinguishable total copper content results for subsamples with
      a wide range of sample masses. Upon pooling all subsample results, an overall
      total copper content for the composite brake wear debris sample was determined to
      be 10.8% (g/g), with a 95% confidence limit of +/- 0.5% (g/g). Copper leaching
      increased with decreasing solid-to-liquid ratios in TCLP tests, but was
      unaffected by the solid-to-liquid ratio in the WET. For a 1:10(4) (g/g) solid-to
      liquid ratio, 85% and 99% of the total mass of copper present in the composite
      brake wear debris sample was leached into solution during the TCLP and WET,
      respectively. Rate studies also demonstrated that the WET resulted in a faster
      rate and higher extent of copper leaching relative to the TCLP. Compared to
      reference copper-containing materials, the composite brake wear debris sample
      exhibited relatively higher TCLP and WET copper leaching characteristics. The
      higher copper leaching exhibited by the brake wear debris sample may have
      resulted from its higher specific surface area and/or from changes in the
      chemical form of copper that occurred during the braking process.

PMID- 14587859
TI  - Prevention of breast cancer--present reality and future promise.

PMID- 14587860
TI  - Prevention of breast cancer using SERMs and aromatase inhibitors.
AB  - Breast cancer is one of the most common cancers of women in the Western world.
      Despite modest achievements in the treatment of this disease, there is a
      substantial unmet medical need to reduce the occurrence of new breast cancers. In
      several prospective, placebo-controlled trials, the antiestrogen tamoxifen has
      been shown to reduce the incidence of both invasive cancer and preinvasive breast
      lesions. Meanwhile, numerous other selective estrogen receptor modulators (SERMs)
      are being developed and trials comparing tamoxifen to these agents are ongoing.
      The goal of these studies is not only to show superior chemopreventive efficacy
      of the newer SERMs, but also an improved side-effect profile. The proof-of
      principle demonstrated with tamoxifen suggests that strategies inhibiting
      estrogen are a logical way forward in breast cancer prevention. Aromatase
      inhibitors, which antagonize estrogen by blocking its synthesis from androgens,
      offer an alternative way of preventing the effects of estrogen and its
      metabolites on the breast. In this paper, the available data on SERMs including
      tamoxifen and raloxifene in breast cancer prevention and the data pointing to the
      efficacy of aromatase inhibitors in this setting are outlined.

PMID- 14587861
TI  - Breast cancer prevention trials using retinoids.
AB  - Retinoids have been studied as chemopreventive agents in clinical trials. Given
      their ability to inhibit mammary carcinogenesis in preclinical models.
      Fenretinide has extensively been investigated because of its favorable
      toxicological profile in humans. In a phase III secondary prevention trial,
      fenretinide showed a trend to a reduction of second breast malignancies in
      premenopausal women but not in postmenopausal women. This pattern was associated
      with a similar modulation of circulating IGF-I. A trend towards a reduction of
      ovarian cancer was also noted. Biomarker studies of fenretinide or novel
      selective retinoids alone and in combination with different nuclear receptor
      ligands are being conducted. These studies provide a model for testing the safety
      and tolerability, pharmacokinetics and pharmacodynamics, and biomarker modulation
      in high-risk women, and offer clues as to both the pathophysiology of
      carcinogenesis and the drug mechanisms of action, and help select new compounds
      and doses for testing in large randomized studies.

PMID- 14587862
TI  - COX-2 inhibitors for the prevention of breast cancer.
AB  - The inducible prostaglandin synthase cyclooxygenase-2 (COX-2) is normally
      expressed predominantly in kidney and brain, and also has important roles in
      reproduction and inflammation. COX-2 misexpression has been observed in numerous
      human cancers, including the majority of colorectal cancers. Recently, COX-2
      overexpression has been described in human breast cancer. COX-2 is present in
      about 40% of invasive breast carcinomas, particularly those that overexpress
      HER2/neu, and COX-2 expression correlates with poor patient prognosis.
      Manipulation of Cox-2 gene dosage by using transgenic overexpression and knockout
      approaches has revealed an important role for Cox-2 in tumorigenesis.
      Furthermore, translational experiments using rodent breast cancer models suggest
      COX-2 inhibition to be an effective strategy for both prevention and treatment of
      experimental breast cancers. Since COX-2 can contribute to multiple facets of
      tumorigenesis, including angiogenesis, several mechanisms are likely to underlie
      the anticancer action of COX inhibitors. Thus, selective COX-2 inhibitors offer
      considerable promise for the prevention and treatment of human breast cancer.

PMID- 14587864
TI  - Novel agents for chemoprevention, screening methods, and sampling issues.
AB  - An aggressive approach to breast cancer control based on preventing the disease
      must complement efforts at effective treatment. To date clinical trials testing
      new chemopreventative agents have not generally met with the kind of success
      expected. A wide range of new breast cancer chemopreventative agents are poised
      to be tested in clinical trials. We review these novel agents and approaches,
      including those for which clinical trials have been initiated and those that are
      promising in the preclinical arena. Further progress in this area requires not
      only new agents, but novel methods for screening for risk assessment, sampling
      and development of intermediate biomarkers. We review these novel potential
      surrogate endpoints, including new imaging-techniques, breast sampling
      approaches, and methods to assess biomarkers in breast epithelium. Factors that
      could contribute to a meaningful choice of the chemopreventive agents and the
      design of clinical trials are discussed.

PMID- 14587865
TI  - Vitamin E and breast cancer prevention: current status and future potential.
AB  - Vitamin E is a collective term used to refer to a number of structurally and
      functionally different compounds. Although some vitamin E compounds are popular
      supplements marketed for their potential beneficial antioxidant effects for a
      number of chronic diseases including various forms of cancer, a recent report by
      the National Academy of Sciences Food and Nutrition Board concluded that too
      little is known at present to provide definitive answers regarding whether taking
      larger doses of dietary antioxidants will help prevent chronic diseases. Recent
      reviews of epidemiological data suggest that dietary source vitamin E may provide
      some protection against breast cancer, while vitamin E supplements do not. A
      majority of studies investigating the protective effects of certain types of
      vitamin E in animal models of mammary cancer prevention conclude that there is
      little or no effect. The study of vitamin E is complex, and the vitamin E field
      faces many scientific challenges.

PMID- 14587867
TI  - Diet and breast cancer: can dietary factors influence survival?
AB  - Breast cancer accounts for over one third of invasive cancers in women. Earlier
      detection and improved initial treatments have resulted in an increasing number
      of women who have completed standard treatments but who remain at risk for breast
      cancer recurrence or early death. Epidemiological studies have linked diet
      composition with prognosis, and many women attempt to modify their diets and
      improve nutritional status following diagnosis The hypothesis that dietary
      factors may reduce risk for secondary cancer events and increase survival in this
      population is currently under study in two large randomized clinical trials: the
      Women's Intervention Nutrition Study (WINS) and the Women's Healthy Eating and
      Living (WHEL) Study. The WHEL Study is testing the effect of a diet high in
      vegetables, fruit, and fiber, and low in fat, on disease-free survival in women
      with early stage breast cancer. Hypothesized mechanisms include effects of diet
      modification on gonadal hormones, retinoid-like activities of carotenoids, and
      other protective effects of biologically active dietary constituents.

PMID- 14587863
TI  - Novel agents for the prevention of breast cancer: targeting transcription factors
      and signal transduction pathways.
AB  - Transformation of breast cells occurs through loss or mutation of tumor
      suppressor genes, or activation or amplification of oncogenes, leading to
      deregulation of signal transduction pathways, abnormal amplification of growth
      signals, and aberrant expression of genes that ultimately transform the cells
      into invasive cancer. The goal of cancer preventive therapy, or
      "chemoprevention," is to eliminate premalignant cells or to block the progression
      of normal cells into cancer. Multiple alterations in signal pathways and
      transcription factors are observed in mammary gland tumorigenesis. In particular,
      estrogen receptor (ER) deregulation plays a critical role in breast cancer
      development and progress, and targeting ER with selective ER modulators (SERMs)
      has achieved significant reduction of breast cancer incidence in women at high
      risk for breast cancer. However, not all breast cancer is prevented by SERMs,
      because 30-40% of the tumors are ER-negative. Other receptors for retinoids,
      vitamin D analogs and peroxisome proliferator-activiator, along with
      transcription factors such as AP-1, NF-kappaB, and STATs (signal transducers and
      activators of transcription) affect breast tumorigenesis. This is also true for
      the signal transduction pathways, for example cyclooxygenase 2 (Cox-2), HER2/neu,
      mitogen-activated protein kinase (MAPK), and PI3K/Akt. Therefore, proteins in
      pathways that are altered during the process of mammary tumorigenesis may be
      promising targets of future chemopreventive drugs. Many newly-developed synthetic
      or natural compounds/agents are now under testing in preclinical studies and
      clinical trials. Receptor selective retinoids, receptor tyrosine kinase
      inhibitors (TKIs), SERMs, Cox-2 inhibitors, and others are some of the promising
      novel agents for the prevention of breast cancer. The chemopreventive activity of
      these agents and other novel signal transduction inhibitors are discussed in this
      chapter.

PMID- 14587869
TI  - Mdm2: A regulator of cell growth and death.
AB  - The interplay between Mdm2 and p53 represents one of the better-known paradigms
      of the relationship between an oncogene and a tumor suppressor gene. The Mdm2
      protein is a key regulator of cell growth and death and plays a pivotal role in
      the transformation of normal cells into tumor cells, the hallmark of an oncogene.
      The primary role of Mdm2 under nonstressed conditions is to target the
      degradation ofthe tumor suppressor protein p53. In response to stress, however,
      p53 is not affected by Mdm2 and functions as a transcription factor that induces
      the transcription of Mdm2 as well as of genes involved in growth control or
      apoptosis. The effect of Mdm2 on the regulation of cell growth and death depends
      on p53 but also on a growing number of p53-independent targets. This overview
      summarizes our current understanding of Mdm2 and p53 regulation, function, and
      interaction in normal and tumor states.

PMID- 14587866
TI  - Prevention of mammary cancer with conjugated linoleic acid: role of the stroma
      and the epithelium.
AB  - Conjugated linoleic acid (CLA), found naturally in dairy products and ruminant
      meats, refers to isomers of octadecadienoic acid with conjugated double bonds.
      CLA inhibits both DMBA- and NMU-induced rat mammary carcinogenesis, and its
      antitumor efficacy is similar whether it is fed only during puberty, or
      continuously during promotion. Pubertal feeding is associated with a reduced
      proliferation of the epithelial cells within the terminal end buds (TEBs) and
      lobular epithelium, and results in a decrease in the epithelial density,
      suggesting a reduction in the carcinogen-sensitive target population. During
      promotion, CLA feeding induces apoptosis of preneoplastic lesions. The effects of
      CLA are mediated by a direct action on the epithelium, as well as by an indirect
      effect through the stroma. CLA is incorporated into the neutral lipids of mammary
      adipocytes, where it can serve as a local reservoir of CLA. Additionally, CLA
      induces the adipogenic differentiation of multipotent mammary stromal cells in
      vitro, and inhibits their development into three-dimensional capillary networks.
      This suggested that CLA might inhibit angiogenesis in vivo, a hypothesis that was
      subsequently confirmed. The antiangiogenic effect is mediated, in part, through a
      CLA-induced decrease in serum VEGF (vascular endothelial growth factor) and
      mammary gland VEGF and flk-1. Together, the data suggest that CLA may be an
      excellent candidate for prevention of breast cancer.

PMID- 14587870
TI  - The systemic progression of human cancer: a focus on the individual disseminated
      cancer cell--the unit of selection.
AB  - The metastatic progression of solid tumors is discussed controversially. Because
      metastasis is usually lethal, it appears as an end point of successive cellular
      changes. This has led to the prevailing interpretation that genetic changes, in
      addition to those present in the most advanced clone of the primary tumor, are
      required to initiate invasion, dissemination, and growth at anatomically distant
      sites. It has become possible to detect and analyze single disseminated cancer
      cells at ectopic sites long before metastasis can be diagnosed by standard
      clinical techniques. Because the finding of single disseminated cancer cells
      correlates with the subsequent development of distant metastasis, these cells
      have been identified as the precursors of metastasis. Their direct molecular
      genetic characterization, however, shows that dissemination occurs very early in
      the process of accumulation of genetic changes and suggests that metastases may
      seldom be derived from the dominant clone of the primary tumor. In contrast, it
      appears that cancer cell evolution explores a multitude of variant cells from
      which systemic cancer can develop independently. This review integrates data
      derived by different approaches into a model of systemic cancer progression.

PMID- 14587868
TI  - Dietary energy restriction in breast cancer prevention.
AB  - Dietary energy restriction (DER) inhibits the development of spontaneous,
      chemically, genetically, and virally induced mammary cancer in rats and/or mice.
      DER inhibits the initiation and postinitiation stages of mammary carcinogenesis
      and the development of both ovarian-hormone-dependent and -independent mammary
      carcinomas. The predominant effect of DER appears to be suppression of the clonal
      expansion of transformed cells, and this effect is most likely mediated via the
      coordinated regulation of cell proliferation, apoptosis, and angiogenesis. The
      effects of DER on cell cycle regulation and apoptosis are consistent with the
      limitation of one or more cell survival factors. Evidence is presented that the
      chemical mediators of this effect, glucocorticoids, insulin, and/or insulin-like
      growth factors, are elicited in response to the limitation in glucose
      availability imposed by DER. Investigation of DER is highly relevant to the
      misregulation of body weight which has been identified as a human health problem
      of global proportion. Mechanistic studies hold the promise of leading to the
      identification of DER mimetic approaches that can be used in the prevention and
      control of breast cancer.

PMID- 14587871
TI  - Seizing of T cells by human T-cell leukemia/lymphoma virus type 1.
AB  - Human T-cell leukemia/lymphoma virus type 1 (HTLV-1) causes neoplastic
      transformation of human T-cells in a small number of infected individuals several
      years from infection. Several viral proteins act in concert to increase the
      responsiveness of T-cells to extracellular stimulation, modulate proapoptotic and
      antiapoptotic gene signals, enhance T-cell survival, and avoid immune recognition
      of the infected T-cells. The virus promotes T-cell proliferation by usurping
      several signaling pathways central to immune T-cell function. Viral proteins
      modulate the downstream effects of antigen stimulation and receptor-ligand
      interaction, suggesting that extracellular signals are important for HTLV-1
      oncogenesis. Environmental factors such as chronic antigen stimulation are
      therefore important, as also suggested by epidemiological data. The ability of a
      given individual to respond to specific antigens is determined genetically. Thus,
      genetic and environmental factors, together with the virus, contribute to disease
      development. As in the case of other virus-associated cancers, HTLV-1-induced
      leukemia/lymphoma can be prevented by avoiding viral infection or by intervention
      during the asymptomatic phase with approaches able to interrupt the vicious cycle
      of virus-induced proliferation of a subset of T-cells. This review focuses on
      current knowledge of the mechanisms regulating HTLV-1 replication and the T-cell
      pathways that are usurped by viral proteins to induce and maintain clonal
      proliferation of infected T-cells in vitro. The relevance of these laboratory
      findings will be related to clonal T-cell proliferation and adult T-cell
      leukemia/lymphoma development in vivo.

PMID- 14587872
TI  - Host cell-dependent expression of latent Epstein-Barr virus genomes: regulation
      by DNA methylation.
AB  - Epstein-Barr virus (EBV) is a ubiquitous human gammaherpesvirus associated with a
      wide spectrum of malignant neoplasms. Expression of latent (growth transformation
      associated) EBV genes is host cell specific. Transcripts for EBV-encoded nuclear
      antigens (EBNAs) are initiated at one of the alternative promoters: Wp, Cp (for
      EBNA1-6), or Qp (for EBNA1 only). Wp is active shortly after EBV infection of
      human B cells in vitro but is progressively methylated and silenced in
      established lymphoblastoid cell lines (LCLs). In parallel Cp, an unmethylated,
      lymphoid-specific promoter is switched on. In contrast, Cp is methylated and
      silent in Burkitt's lymphoma (BL) cell lines, which keep the phenotype of BL
      biopsy cells (group I BL lines). These cells use Qp for the initiation of EBNA1
      messages. Qp is unmethylated both in group I BLs (Qp on) and in LCLs (Qp off).
      Thus, DNA methylation does not play a role in silencing Qp. In LCLs and
      nasopharyngeal carcinoma (NPC) cells, transcripts for latent membrane protein 1
      (LMP1) are initiated from LMP1p, a promoter regulated by CpG methylation. LMPlp
      is silent in group I BL lines but can be activated by demethylating agents.
      Promoter silencing by CpG methylation involves both direct interference with
      transcription factor binding (Wp, Cp) and indirect mechanisms involving the
      recruitment of histone deacetylases (LMPlp). A dyad symmetry sequence(DS) within
      oriP (the latent origin of EBV replication) and intragenic RNA polymerase III
      control regions of EBER 1 and 2 transcription units are invariably unmethylated
      in EBV-carrying cells.

PMID- 14587873
TI  - Gene expression profiling of renal cell carcinoma and its implications in
      diagnosis, prognosis, and therapeutics.
AB  - Renal cell carcinoma (RCC) is the 10th most common cancer in the United States.
      It is a histologically heterogeneous disease with various histologic types being
      characterized by distinct genetic alterations. This chapter reviews advances in
      the gene expression profiling of RCC and discusses their clinical implications.
      Data are promising, and many more RCC-related microarray studies are currently
      underway or in planning. Undoubtedly these data will have an impact on the
      diagnosis, prognosis, and treatment of RCCs in the future. Finally, this chapter
      discusses what additional studies should be performed to help uncover the
      molecular mechanisms of RCC and to bring this new knowledge into use in the
      clinical arena.

PMID- 14587874
TI  - Role of component herbs in antioxidant activity of shengmai san--a traditional
      Chinese medicine formula preventing cerebral oxidative damage in rat.
AB  - Traditional Chinese medicine (TCM) is an attractive model for studying
      antioxidant-based composite therapy. We previously reported that Shengmai San
      (SMS), a TCM formulation for treating cardiac disorders, inhibited cerebral
      oxidative damage in rats when evaluated by both glutathione peroxidase (GPX)
      activity loss and thiobarbituric acid reactive substance (TBARS) formation after
      forebrain ischemia-reperfusion. In the present study, we further examined the
      preventive effect of SMS and related decoctions composed of three component herbs
      (Panax ginseng, Ophiopogon japonicus and Schisandra chinensis) against oxidative
      brain injury to rationalize the complex formulation of SMS. Schisandra chinensis
      itself and decoctions containing it all inhibited TBARS formation in vivo. In
      contrast, Ophiopogon japonicus itself and formulations containing it had little
      effect on TBARS formation. GPX activity loss in vivo, on the other hand, was
      completely prevented only by SMS and Ophiopogon japonicus itself. A comparison of
      the in vitro antioxidant potential of SMS and related decoctions and in vivo
      effectiveness in preventing cerebral oxidative damage revealed that all the in
      vitro antioxidant indices examined here essentially correlated well with
      inhibition of TBARS formation in vivo. DPPH quenching and crocin bleaching
      activities showed particularly good correlation, and then, superoxide scavenging
      activity followed. However, none of them correlated with the inhibition of GPX
      activity loss in vivo. The role of each component herb is also discussed for the
      SMS effect.

PMID- 14587876
TI  - Effect of one week treatment with Ginkgo biloba extract (EGb761) on ischemia
      induced infarct volume in gerbils.
AB  - The present study was designed to evaluate the neuroprotective effects of Ginkgo
      biloba leaf extract (EGb761) in male gerbils subjected to focal cerebral ischemia
      produced by permanent occlusion of the right middle cerebral artery. In this
      study, gerbils were fed standard chow with or without EGb761 (100 mg/kg/day,
      i.g.) prior to cerebral ischemia for 1 week. Gerbils were anesthetized and
      craniectomized to expose the right middle cerebral artery (MCA). The right MCA
      was constricted with an 8-0 suture to produce a permanent ligation. Infarct
      volume was assessed by TTC (2,3,5-triphenyl-tetrazolium chloride) staining 24
      hours after initiation of cerebral ischemia. Results showed that the EGb761 group
      had significant reduction of infarct volume 4 and 6 mm from the frontal pole by
      40% and 30%, respectively when compared to the control group (p < 0.05). Mean
      locomotor activity of gerbils was reduced 24 hours after the occlusion of the MCA
      in both groups. However, there was no difference in locomotor activity between
      groups either 30 minutes before or 24 hours after the occlusion (p > 0.05).

PMID- 14587875
TI  - Antioxidative and antimutagenic activities of healthy herbal drinks from Chinese
      medicinal herbs.
AB  - Twenty-nine Chinese medicinal herbs and three healthy herbal drinks made of those
      herbs in a food processing pilot plant were tested for their antioxidative, free
      radical scavenging, mutagenic and antimutagenic activities. Water extracts of
      herbs (with few exceptions) and herbal drinks showed free radical scavenging
      activity. All water extracts of herbs and herbal drinks showed no mutagenicity
      toward Salmonella typhimurium tester strains TA98 and TA100 used in the Ames
      mutagenic tests. In the antimutagenic tests, the mutagenic activity of 4
      nitroquinoline N-oxide (NQNO) toward S. typhimurium TA98 was markedly inhibited
      by water extracts of herbs and herbal drinks. Based on the results, it is
      suggested that the herbal drinks manufactured in pilot-plant scale are safe and
      can be served as health-promoting drinks for the public.

PMID- 14587877
TI  - The ameliorating effects of cognition-enhancing Chinese herbs on scopolamine- and
      MK-801-induced amnesia in rats.
AB  - The study was to investigate the ameliorating effects of three Chinese herbs-
      Achyranthes bidentata (AB), Ophiopogon japonicus (OJ) and Cnidium monnieri (CM)
      on scopolamine (SCOP)- and MK-801-induced amnesia by using a passive avoidance
      task in rats. AB, OJ and CM at 0.1 and 0.3 g/kg prolonged the step-through
      latency (STL) of the retention trial. In addition, AB, OJ and CM reversed the STL
      shortened by MK-801, but only AB reversed the STL shortened by SCOP. In
      conclusion, these Chinese herbs possess cognition-enhancing activities and anti
      amnestic effects, but the mechanism of the effect of AB was different from those
      of OJ and CM.

PMID- 14587878
TI  - Induction of apoptosis in HL-60 cells treated with medicinal herbs.
AB  - In order to develop a new apoptosis inducer, we screened 22 crude drugs for their
      apoptosis-inducing activity. It was found that Glycyrrhiza uralensis, Cynomorium
      songaricum, Eucommia ulmoides, Phellodendron amurense, Cinnamomum cassia and
      Paeonia lactiflora induced the death of HL-60 cells. To investigate the mechanism
      of apoptosis induced by these six crude drugs, the mitochondrial transmembrane
      potential and the activity of caspase-3 were measured. Reduced mitochondrial
      transmembrane potentials within 12 hours after the administration of Glycyrrhiza
      uralensis, Cynomorium songaricum, Phellodendron amurense and Paeonia lactiflora,
      and within 24 hours after the administration of Eucommia ulmoides and Cinnamomum
      cassia were observed. All of the six apoptosis-inducing crude drugs increased
      caspase-3 activity within 12-36 hours after administration. After further
      examining the apoptosis-inducing activity of berberine, palmatine, panelofuroline
      and glycyrrhizin, which were the ingredients obtained from Phellodendron
      amurense, Glycyrrhiza uralensis and Paeonia lactiflora, it was found that only
      berberine could induce apoptosis. From these results, it was concluded that the
      apoptosis induced by the six crude drugs (Glycyrrhiza uralensis, Cynomorium
      songaricum, Eucommia ulmoides, Phellodendron amurense, Cinnamomum cassia and
      Paeonia lactiflora) occurred via the mitochondrial route and that the apoptosis
      conducting mechanism acted through a cascade involving caspase-3.

PMID- 14587879
TI  - Effects of aqueous extract of Sophora flavescens on the expression of cell cycle
      regulatory proteins in human oral mucosal fibroblasts.
AB  - Sophorae Radix, the dried roots of Sophora flavescens AITON (Leguminosae), has
      been used in Oriental traditional medicine for treatment of skin and mucosal
      ulcers, sores, gastrointestinal hemorrhage, diarrhea, inflammation and
      arrhythmia. In the present study, we examine the effect of the aqueous extract of
      Sophorae Radix (AESR) on cell proliferation and cell cycle regulation in human
      oral mucosal fibroblasts (HOMFs). To study the molecular mechanisms of cell cycle
      regulation by AESR, we also measured the intracellular levels of cell cycle
      regulatory proteins such as cyclin D, cyclin-dependent kinases (CDK)-4, CDK-6,
      cyclin E, CDK-2, p53, p21WAF1/CIP1 and p16INK4A. Cell proliferation was increased
      in the presence of 10 approximately 500 microg/ml of AESR. Maximal growth
      stimulation was observed in those cells exposed to 100 microg/ml of AESR.
      Exposure of HOMFs to 100 microg/ml of AESR resulted in an increase of cell cycle
      progression. The levels of cyclin E and CDK-2 were increased in HOMFs after 100
      microg/ml of AESR treatment, but the levels of cyclin D, CDK-4, and CDK-6 were
      unchanged. After exposure to 100 microg/ml of AESR, the protein levels of
      p16INK4A and p53 were decreased as compared to that of the control group, but the
      level of p21WAF1/CIP1 was similar in the cells treated with 100 microg/ml of AESR
      and untreated cells. The results suggest that AESR may increase cell
      proliferation and cell cycle progression in HOMFs, which is linked to increased
      cellular levels of cyclin E and CDK-2 and decreased cellular levels of p53 and
      p16INK4A. Further studies are necessary to clarify the active constituents of
      AESR responsible for such biomolecular activities.

PMID- 14587880
TI  - Effects of Shao-Fu-Zhu-Yu-Tang on motility of human sperm.
AB  - Shao-Fu-Zhu-Yu-Tang (SFZYT) is reportedly beneficial to sperm. In this study, we
      examined sperm acrosomal activity and serum free radical changes to evaluate the
      possible mechanism of SFZYT. A clinical study evaluated the sperm count and
      motility in 36 patients with chronic prostatitis before and after treatment for
      60 days. The results revealed a significant increase in sperm motility after
      treatment as evaluated by computer-assisted semen analysis (17.27 +/- 9.00 versus
      28.29 +/- 10.00, p < 0.01). An increase in sperm quantity and quality was
      observed by count and morphology with a high-powered intravital microscope. To
      gain an understanding of the mechanisms that caused this effect, we assessed
      sperm acrosin activity levels before (10.6 micro lu/10(6)) and after medication
      (28.6 micro lu/10(6)) (p < 0.01). The levels of the free radicals was relatively
      higher before medication, 2144, compared to a normal value of 780 after
      medication (p < 0.01). In conclusion, SFZYT increased the motility and quality of
      human semen and this increase is related to an increase in sperm acrosin
      activity. SFZYT also works as a sperm antioxidant and antiaging agent.

PMID- 14587881
TI  - Acupuncture modulates expressions of nitric oxide synthase and c-Fos in
      hippocampus after transient global ischemia in gerbils.
AB  - The effects of acupuncture on the expressions of nitric oxide synthase (NOS) and
      c-Fos in the hippocampus of gerbils after transient ischemia were investigated
      via nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d)
      histochemistry and Fos immunohistochemistry. In animals of the ischemia-induction
      groups, both common carotid arteries were occluded for 5 minutes. Animals of the
      acupunctued groups were given acupunctural treatment at Zusanli twice daily for 9
      consecutive days. Acupuncture was shown to decrease NADPH-d and c-Fos levels in
      both the sham-operation group and the ischemia-induction group. These results
      suggest that acupuncture modulates the expressions of NOS and c-Fos in the
      hippocampus.

PMID- 14587882
TI  - A study on the central neural pathway of the heart, Nei-Kuan (EH-6) and Shen-Men
      (He-7) with neural tracer in rats.
AB  - The purpose of this morphological study was to investigate the relations between
      meridians, acupoints and viscera using neuroanatomical tracers. The labeled areas
      of the spinal ganglia, sympathetic chain ganglia, spinal cord and the brain
      projecting to the heart, Nei-Kuan (EH-6) and Shen-Men (He-7) were observed
      following injection of WGA-HRP and pseudorabies virus (PRV). The results were as
      follows. Overlapping bilaterally labeled ganglion areas after heart, Nei-Kuan (EH
      6) or Shen-Men (He-7) injection of WGA-HRP were found in middle cervical,
      stellate and T4 sympathetic and T2-T6 spinal ganglia. In brain, labeled neurons
      from all three sites were found in the A1 noradrenalin cell group/C1 adrenalin
      cell group/caudoventrolateral reticular n., n. tractus solitarius, n. ambiguus,
      rostroventrolateral n., C3 adrenaline cell group, raphe obscurus n., raphe
      pallidus n., raphe magnus n., lateral paragigantocellular reticular n., locus
      coeruleus, subcoeruleus n., Kolliker-Fuse n., A5 cell group, central gray matter,
      paraventricular hypothalamic n. and arcuate hypothalamic n.. In conclusion, these
      morphological results suggest that the interrelationship of acupoints (Nei-Kuan
      and Shen-Men) and viscera (heart) may be related to the central autonomic centers
      of the spinal cord and brain.

PMID- 14587883
TI  - Effect of moxibustion stimulation of various skin areas on cortical cerebral
      blood flow in anesthetized rats.
AB  - The effect of moxibustion stimulation of various skin areas (cheek, forepaw,
      upper arm, chest, back, lower leg, hindpaw and perineum) on cerebral blood flow
      (CBF) of the parietal cortex was examined in anesthetized rats after eliminating
      emotional influences. Moxibustion stimulation was performed by burning a moxa
      cone of about 4 mg weight placed on the shaved skin. CBF of the parietal cortex
      was measured using a laser Doppler flowmeter. Stimulation of the cheek, forepaw,
      upper arm and hindpaw produced significant increases in CBF, but stimulation of
      the other areas did not produce significant responses. Moxibustion stimulation of
      the forepaw and hindpaw produced an increase in the mean arterial pressure (MAP),
      while stimulation of the other areas did not. After spinal transection at the 2nd
      thoracic level, the MAP response to stimulation of the forepaw was abolished,
      whereas the CBF response to stimulation of the forepaw remained. The CBF response
      in spinalized rats was not affected by cutting cervical sympathetic and facial
      parasympathetic nerves, while it was almost abolished by intravenous
      administration of muscarinic and nicotinic cholinergic blocking agents. The CBF
      response was abolished by crushing the brachial plexus ipsilateral to the
      stimulated side. It is suggested that the increase in CBF, independent of MAP and
      emotional responses, elicited by moxibustion stimulation is a reflex response
      whose afferent pathway is composed of somatic afferent nerves, and whose efferent
      pathway involves intracerebral cholinergic nerves. A contribution of endogenous
      opioids in the present CBF responses was neglected, because naloxone did not
      influence the CBF responses.

PMID- 14587884
TI  - Effects of in vitro and in vivo Qi-therapy on neutrophil superoxide generation in
      healthy male subjects.
AB  - The present study investigated the effects of in vitro and in vivo Korean ChunSoo
      Qi-Energy Healing on neutrophil superoxide generation. Neutrophil superoxide
      generation was measured by a chemiluminescence assay. Superoxide generation was
      significantly increased in vitro by emitted Qi-therapy (QT) of 60-second duration
      and 150-second duration compared to control (1.59-fold for 60 seconds, p < 0.05;
      1.50-fold for 150 seconds, p < 0.05). Neutrophil superoxide generation increased
      significantly immediately after 5 minutes of QT in vivo (1.42-fold, p < 0.05).
      These results show that QT in vivo and in vitro has an acute stimulatory effect
      on neutrophil superoxide generation. This study provides direct scientific
      support that Qi as such may positively affect human innate immunity.

PMID- 14587885
TI  - EEG alpha blocking correlated with perception of inner light during zen
      meditation.
AB  - According to the experimental results and practitioners' subjective experience,
      we report some hypotheses that may account for meditative phenomena during the
      practice of Zen-Buddhism. Orthodox Zen-Buddhist practitioners, aiming to prove
      the most original true-self, discover and uncover the inner energy or light on
      the way towards their goal. Perception of the inner light can be comprehended as
      resonance. Uncovering the inner energy optimizes physiological and mental health.
      In the meditation experiment, a significant correlation was observed between
      perception of the inner light and electroencephalographic (EEG) alpha blockage.
      We further examined this phenomenon by recording the EEG from subjects during a
      blessing that the subjects did not know being given. During the blessing period,
      significant alpha blocking was observed in experimental subjects who had been
      practicing meditation for years in preparation for being in resonance with the
      inner light. This report provides a new insight into the debate that meditation
      benefits our health.

PMID- 14587886
TI  - Challenge tests and kampo medicines: case report and review of the literature.
AB  - In order to diagnose Kampo medicine-induced liver injury, a challenge test using
      the suspected medicine is the most reliable method of assessing the relationship
      between Kampo medication and liver injury. However, such a challenge test may
      cause severe liver injury. We examined the clinical features and safety of
      challenge tests conducted by a physician in a case of Kampo medicine-induced
      liver injury that we encountered as well as in the previous literature (six
      cases) in Japan. In all cases except two, one-third of the daily dose was given a
      few times for the challenge test (challenge dose was not described in two cases).
      The reaction induced by the challenge peaked 1-3 days after challenge. Mild
      eosinophilia (6%) was observed in two cases. All liver injuries induced by
      challenge cleared within 2 weeks, and neither severe nor fatal liver injury was
      observed. In conclusion, a challenge with a small dose of Kampo medicine
      conducted in our case and in the previous literature induced mild and reversible
      liver injury. The safety and availability of challenge with a small dose of Kampo
      medicine should be further examined in a larger population with Kampo medicine
      induced liver injury.

PMID- 14587887
TI  - Pattern of alternative medicine usage among the Chinese breast cancer patients:
      implication for service integration.
AB  - The study examined the pattern of and factors associated with use of alternative
      medicine (AM) among Chinese breast cancer patients. An analytical, cross
      sectional survey of 352 breast cancer patients from two breast cancer centers was
      conducted in 1997. Amongst the respondents, the usage rate of alternative
      medicine was 27.8%. Factors forming the use of AM included being young to middle
      aged, having higher education and a belief that AM would enhance orthodox
      treatment. A substantial proportion of Chinese breast cancer patients use AM
      besides conventional medicine. There is a need to integrate AM with conventional
      medicine to improve the service provision for cancer patients.

PMID- 14587888
TI  - Effect of sairei-to combined with aspirin and prednisolone on four recurrent
      reproductive failure women who are positive for anti-phospholipid antibodies.
AB  - We treated four pregnancy cases positive for antiphospholipid antibodies (APLs)
      who had experienced recurrent second trimester fetal or neonatal losses using a
      Japanese modified Chinese herbal medicine, Sairei-to, low dose aspirin and
      adrenocorticosteroid hormone. The clinical courses of their new pregnancies in
      conjunction with the dynamic changes in their APL titers are described in this
      paper, and the possible efficacy of this treatment is discussed. The concept that
      autoimmune abnormalities, especially positive APLs, are generative factors for a
      range of reproductive failures, such as recurrent abortions, intrauterine growth
      retardation, intrauterine fetal death and preeclampsia, is now attracting a great
      deal of attention in the fields of reproductive immunology and perinatal medicine
      (Yasuda et al., 1995). The main mechanisms in the generation of reproductive
      failures are considered to be direct damage to chorionic villi by APLs during the
      period of placentation (Rote et al., 1998), as well as the formation of thrombi
      intervillous spaces (Arakawa et al., 1999). Considering these mechanisms of the
      reproductive failure generation by APLs, the application of immune suppressive
      therapy in combination with anti-coagulation therapy should be reconsidered as a
      treatment option. In this context, we treated four pregnancy cases positive for
      APLs who had experienced recurrent second trimester fetal or neonatal losses
      using a Japanese modified Chinese herbal medicine, Sairei-to, low dose aspirin
      and an adrenocorticosteroid hormone.

PMID- 14587889
TI  - Comment on "Hydrocarbon composition and toxicity of sediments following the Exxon
      Valdez oil spill in Prince William Sound, Alaska, USA".

PMID- 14587890
TI  - The effects of ammonia on freshwater unionid mussels.

PMID- 14587891
TI  - Sensitivity of juvenile freshwater mussels (Lampsilis fasciola, Villosa iris) to
      total and un-ionized ammonia.
AB  - This study evaluated the sensitivity of juveniles of two freshwater unionid
      mussel species (Villosa iris [Lea] and Lampsilis fasciola [Rafinesquel) to un
      ionized and total ammonia. Five concentrations of ammonium chloride were tested
      using 96-h static-renewal toxicity tests at 12 and 20 degrees C. Based on their
      respective mean 96-h lethal concentration to 50% (LC50s), V. iris (0.11 mg/ L NH3
      N) was more sensitive than L. fasciola (0.26 mg/L NH3-N). At 96 h, significant
      differences in sensitivity to un-ionized ammonia between the two temperatures
      were not observed for either species. Comparison of LC50s reported for other
      aquatic organisms to the 96-h LC50s calculated for juvenile L. fasciola and V.
      iris shows these two mussel species to be among the most sensitive to un-ionized
      ammonia. Based on reported levels of un-ionized ammonia in the aquatic
      environment from anthropogenic sources, un-ionized ammonia may be an important
      limiting toxicological factor to freshwater mussel populations.

PMID- 14587892
TI  - Effects of ammonia on juvenile unionid mussels (Lampsilis cardium) in laboratory
      sediment toxicity tests.
AB  - Ammonia is a relatively toxic compound generated in water and sediments by
      heterotrophic bacteria and accumulates in sediments and pore water. Recent data
      suggest that unionid mussels are sensitive to un-ionized ammonia (NH3) relative
      to other organisms. Existing sediment exposure systems are not suitable for
      ammonia toxicity studies with juvenile unionids; thus, we modified a system to
      expose juveniles to ammonia that was continuously infused into sediments. This
      system maintained consistent concentrations of ammonia in pore water up to 10 d.
      Juvenile Lampsilis cardium mussels were exposed to NH3 in pore water in replicate
      96-h and 10-d sediment toxicity tests. The 96-h median lethal concentrations
      (LC50s) were 127 and 165 microg NH3-N/L, and the 10-d LC50s were 93 and 140
      microg NH3-N/L. The median effective concentrations (EC50s) (based on the
      proportion affected, including dead and inactive mussels) were 73 and 119 microg
      NH3-N/L in the 96-h tests and 71 and 99 microg NH3-N/L in the 10-d tests. Growth
      rate was substantially reduced at concentrations between 31 and 76 microg NH3
      N/L. The lethality results (when expressed as total ammonia) are about one-half
      the acute national water quality criteria for total ammonia, suggesting that
      existing criteria may not protect juvenile unionids.

PMID- 14587893
TI  - Effects of pore-water ammonia on in situ survival and growth of juvenile mussels
      (Lampsilis cardium) in the St. Croix Riverway, Wisconsin, USA.
AB  - We conducted a series of in situ tests to evaluate the effects of pore-water
      ammonia on juvenile Lampsilis cardium in the St. Croix River (WI, USA). Threats
      to this river and its associated unionid fauna have accelerated in recent years
      because of its proximity to Minneapolis-St. Paul, Minnesota, USA. In 2000, caged
      juveniles were exposed to sediments and overlying water at 12 sites for 10 d.
      Survival and growth of juveniles was significantly different between sediment
      (mean, 47%) and water column (mean, 86%) exposures; however, these effects were
      unrelated to pore-water ammonia. During 2001, juveniles were exposed to sediments
      for 4, 10, and 28 d. Pore-water ammonia concentrations ranged from 0.3 to 62.0
      microg NH3-N/L in sediments and from 0.5 to 140.8 microg NH3-N/L within exposure
      chambers. Survival (mean, 45, 28, and 41% at 4, 10, and 28 d, respectively) and
      growth (range, 3-45 microm/d) of juveniles were highly variable and generally
      unrelated to ammonia concentrations. Although laboratory studies have shown
      unionids to be quite sensitive to ammonia, further research is needed to identify
      the route(s) of ammonia exposure in unionids and to understand the factors that
      contribute to the spatial variability of ammonia in rivers.

PMID- 14587894
TI  - Water quality guidance for protection of freshwater mussels (Unionidae) from
      ammonia exposure.
AB  - Ammonia toxicity data for freshwater mussels (Unionidae), a significantly
      imperiled taxa, were used to derive estimates of concentrations that would not
      likely be harmful in acute and chronic exposures and to assess the protectiveness
      of current U.S. Environmental Protection Agency (U.S. EPA) water quality criteria
      to this family of organisms. Thirty acute (24-96-h) median lethal concentrations
      (LC50s), covering 10 species in eight unionid genera, were used to calculate
      genus mean acute values (GMAVs) ranging from 2.56 to 8.97 mg/L total ammonia as N
      at pH 8. Freshwater mussels are at the sensitive end of the range when added to
      the GMAVs from the database used to derive the U.S. EPA criteria maximum
      concentration (CMC). We derived two estimates of acute exposure water quality
      guidance for the protection of freshwater mussels (CMC(FM)) by a recalculation of
      the CMC after adding freshwater mussel GMAVs to the U.S. EPA data set. The
      CMC(FM)s of 1.75 and 2.50 mg/L total ammonia as N at pH 8 average 60% less than
      the U.S. EPA CMC of 5.62 mg/L total ammonia as N at pH 8 for application when
      salmonids are present. These values average about 75% less than the CMC for
      application when salmonids are absent. No chronic ammonia exposure data existed
      for unionids. Thus, we applied a range of estimated acute:chronic ratios to the
      acute toxicity data set, expanded with the freshwater mussel GMAVs. to estimate
      continuous ammonia concentrations that may be protective of freshwater mussels.
      These estimates ranged from 0.3 to 1.0 mg/L total ammonia as N at pH 8, about 20
      to 75% less than the U.S. EPA criteria continuous concentration (CCC) of 1.24
      mg/L total ammonia as N at pH 8 and 25 degrees C. The current numeric criteria
      for ammonia may not be protective of mussels, more than half of whose nearly 300
      species are in decline in North America. While the CMC(FM) and CCC(FM) are not
      equivalent to revised U.S. EPA criteria, they are offered as interim guidance for
      the protection of freshwater mussels.

PMID- 14587895
TI  - Assessment of the mutagenic potency of sewage sludges contaminated with
      polycyclic aromatic hydrocarbons by an Ames sludges for fluctuation assay.
AB  - The mutagenicity of crude extracts and subfractions of two samples of a reference
      sewage sludge material and two sewage sludges from two wastewater treatment
      plants (WWTP), one urban and the other one urban mixed with industrial, was
      assessed using an Ames fluctuation assay based on 384-well microtiter plates with
      liquid cultures. Crude extracts of sludges were obtained by ultrasonic extraction
      with dichloromethane/methanol, and further column fractionation yielded two
      fractions, one of which containing mutagenic polycyclic aromatic hydrocarbons
      (PAHs). Quantitative analysis performed by gas chromatography-mass spectrometry
      gave sum concentrations of the 16 PAHs listed as priority pollutants by the U.S.
      Environmental Protection Agency at levels between 1,305 and 2,442 microg/kg.
      Subjecting crude extracts and column fractions to the mutagenicity assay with
      Salmonella strains TA98 and TA 100 provided good qualitative correlation between
      the presence of mutagenic PAH and the induction of gene mutations. In general,
      the crude extracts and the PAH-fractions induced positive responses in the assay
      with both bacterial strains on metabolic activation by S9 rat-liver homogenate,
      whereas direct-acting mutagens were not detectable. In the assay with the real
      sludge samples of two different WWTPs, TA98 proved to be more sensitive than
      TA100; however, similar sensitivities of the tester strains were observed for two
      reference sewage sludge materials of the same origin. The outcomes of the Ames
      fluctuation assay demonstrated its performance as a cost-effective and relatively
      rapid screening tool to assess the genotoxic potential of complex environmental
      samples.

PMID- 14587896
TI  - Lead and stable lead isotope ratios in soil, earthworms, and bones of American
      woodcock (Scolopax minor) from eastern Canada.
AB  - A study to discriminate among different possible sources of elevated Pb exposure
      for American woodcock (Scolopax minor) in eastern Canada is described. Undamaged
      wing bones excised from young-of-the-year woodcock collected from several
      locations in southern Ontario, southern Quebec, New Brunswick, and Nova Scotia,
      Canada, along with soil and earthworm (Aporrectodea tuberculata and Lumbricus
      rubellus) samples from the same sites, were analyzed for total Pb, and stable Pb
      isotopes. Ignoring six soil samples with high (> 60 microg/g) Pb concentration
      from the vicinity of Montreal (QC, Canada), the mean soil-Pb concentration for
      all sites combined was 19 microg/g (dry wt; n = 64), with a mean 206Pb:207Pb
      ratio of 1.19, values typical for uncontaminated rural soils in eastern North
      America. In earthworms, Pb concentrations ranged from 2.4 to 865 (microg/g [dry
      wt], mean = 24 microg/g). Concentrations of Pb in worms and soils were positively
      correlated (r = 0.71; p < 0.01), and 206Pb:207Pb ratios for worms and soils were
      also positively correlated (r = 0.54; p < 0.05). However, most young-of-the-year
      woodcock with high bone-Pb accumulation (> 20 microg/g) had 206Pb:207Pb ratios
      substantially different from worms and soils sampled from the same areas, even
      though woodcock feed extensively on soil invertebrates, especially earthworms.
      The range of 206Pb:207Pb ratios in wing bones of woodcock with elevated Pb
      exposure was not consistent with exposure to environmental Pb from past gasoline
      combustion nor Precambrian mining wastes but was consistent with ingestion of
      spent Pb shotgun pellets.

PMID- 14587897
TI  - Comparison of toxicity of zinc for soil microbial processes between laboratory
      contamined and polluted field soils.
AB  - Soil microbial processes are readily disturbed by added zinc (Zn) in laboratory
      ecotoxicity tests. This study compares Zn toxicity between freshly spiked soils
      and soils that have been contaminated with Zn in the field. Soils were sampled in
      three transects (< 80 m) toward galvanized electricity transmission towers
      (pylons). The soil total Zn concentrations gradually increased in each transect
      from background values (25-82 mg Zn/kg) to elevated Zn concentrations near the
      pylon (226-595 mg Zn/kg). Soil samples taken at the furthest distance from the Zn
      source were spiked with ZnCl2 to a range of total Zn concentrations similar to
      those in the transect. Nitrification, respiration, and N-mineralization rates
      were significantly reduced by added Zn in laboratory-spiked soils and were 9 to
      95% (mean 32%) of the control values at largest doses depending on soil type and
      the microbial process. In contrast, these processes were either unaffected by
      soil Zn (p > 0.05) or increased significantly with soil Zn concentrations in the
      transect soils. These increases could not be explained by soil pH or % soil
      organic carbon. Leaching soils after spiking significantly lowered the toxic
      effects of Zn on nitrification or on substrate-induced respiration. The soil
      solution Zn concentrations of field soils were always smaller than in spiked
      soils at equivalent total Zn. Highest soil solution Zn concentrations were always
      lower than the soil-solution EC50s of spiked soils. It is concluded that there is
      a large discrepancy in microbial responses to elevated Zn between spiked soils
      (unleached) and field-contaminated soils and there is a need to explain this
      discrepancy in terms of Zn availability, adaptation processes, and additional
      soil factors controlling the microbial processes.

PMID- 14587898
TI  - Effect of nonaqueous-phase liquids on the availability of polycyclic aromatic
      hydrocarbons in soil for worm uptake and bacterial genotoxicity.
AB  - A study was conducted to determine the effect of nonaqueous-phase liquids (NAPLs)
      on the bioavailability of benzo[a]pyrene (BaP) in soil. Sentry 19 oil and
      pristane reduced the availability of BaP for assimilation by the earthworm
      Eisenia fetida and for mutagenicity in a rifampicin-sensitive strain of
      Pseudomonas putida. As much as 80% of the compound could be rendered unavailable
      to the worms or for genotoxicity. Tests with five alkanes and an oil showed that
      the extent of reduction in genotoxicity of BaP varied with the identity,
      viscosity, and hydrophobicity of the NAPL. The magnitude of the decline in
      availability for genotoxicity differed in tests of three soils. Because little or
      no BaP was lost from the soil, the diminished bioavailability was not the result
      of a diminished total concentration of the compound. These findings show that
      exposure to hydrophobic toxicants can be appreciably altered in soils containing
      NAPLs.

PMID- 14587899
TI  - Concentrations of organochlorine pesticides and polychlorinated biphenyls in
      amphipods (Gammarus lacustris) along an elevation gradient in mountain lakes of
      western Canada.
AB  - Populations of the amphipod Gammarus lacustris were examined for their
      concentrations of organochlorine pesticides and polychlorinated biphenyls (PCBs)
      from seven lakes spanning a 1,300-m elevation gradient in Alberta, Canada. The
      concentrations of several of the semivolatile organochlorine compounds ([SVOCs],
      vapor pressure > 0.03 Pa at 20 degrees C) increased at higher altitudes. This
      pattern was generally not observed among the less volatile organochlorines
      ([LVOCs]. vapor pressure < 0.03 Pa at 20 degrees C). These same SVOC compounds
      have been previously shown to increase at high latitudes as a result of their
      long-range transport and preferential deposition in cold climates. We also show
      that populations of G. lacustris at high elevations have slower growth rates and
      store more lipids than populations at lower elevations. To resolve the
      colinearity of independent variables, we used multiple regression to identify
      patterns of contaminant concentrations in this data set. Multiple regressions
      showed that the effect of elevation, lipid content, and temperature on
      contaminant concentrations was no longer significant once the growth rate of
      Gammarus was included as an independent variable. This study shows that
      enrichment of SVOCs occurs in Gammarus at high altitudes in Alberta, Canada, and
      that growth rate (biodilution) appears to be the primary influence. Because
      Gammarus is an important trophic link in aquatic foodwebs in these environments,
      enhanced concentrations of toxicants in prey may increase their biomagnification
      in top predators of high-altitude lakes.

PMID- 14587900
TI  - Anaerobic transformation of compounds of technical toxaphene. I. Regiospecific
      reaction of chlorobornanes with geminal chlorine atoms.
AB  - Technical toxaphene (Melipax) and the single compounds of technical toxaphene
      (CTTs) 2,2,5-endo,6-exo,8,8,9,10-octachlorobornane (B8-806), 2,2,5-endo,6-exo,
      8,9,9,10-octachlorobornane (B8-809), 2,2,5,5,8,9,9,10,10-nonachlorobornane (B9
      1025), 2-endo,3-exo,5-endo,6-exo,8,8,9,10,10-nonochlorobornane (B9-1679), 2
      endo,3-exo,5-endo,6-exo,8,9,10,10-octachlorobornane (B8-1414), 2-endo,3-exo,5
      endo,6-exo,8,8,9,10-octachlorobornane (B8-1412), and 2-exo,3-endo,5-exo,9,9,10,10
      heptachlorobornane (B7-1453) were treated with suspensions of the anaerobic
      bacterium Dehalospirillum multivorans. After 7 d, more than 50% of technical
      toxaphene was transformed, and the relative amount of early eluting CTTs
      increased. After 16 d, only 2-exo,3-endo,6-exo, 8,9,10-hexachlorobornane (B6
      923), 2-endo,3-exo,5-endo,6-exo, 8,9,10-heptachlorobornane (B7-1001), and a few
      minor penta- and hexachloro-CTTs were detected in the samples. The result of the
      transformation was comparable with observations in naturally contaminated
      sediments and soil. However, the performance with D. multivorans was more simple
      and reproducible, as well as faster, than use of soil, sediment, or anaerobic
      sewage sludge. In agreement with reports in the literature, reductive
      dechlorination at geminal chlorine atoms (gem-C1s) was found to be the major CTT
      transformation pathway. Experiments conducted with CTTs and gem-C1s at both
      primary and secondary carbons clarified that the initial C1 --> H substitution
      takes place at the secondary carbon C2. Furthermore, the 2-endo-C1 position was
      preferably substituted with hydrogen. In the case of B8-806, the dechlorination
      at the secondary carbon C2 was approximately 20-fold faster than the subsequent,
      slow reduction at the primary carbon C8. The three different formerly unknown
      heptachloro-CTTs, 2-exo,3-endo,6-exo,8,9,9,10-heptachlorobornane (B7-1473), 2
      exo, 3-endo,6-endo,8,9,9,10-hepatchlorobornane (B7-1461), and 2-exo, 3-endo,6
      exo,8,8,9,10-heptachlorobornane (B7-1470) were found as intermediates of the B8
      806/809 transformation. Treatment of B9-1679 with D. multivorans indicated that
      gem-C1s on the bridge (C8 and C9) are dechlorinated faster than gem-C1s on the
      bridgehead (C10).

PMID- 14587901
TI  - Quantification of steroid hormones with pheromonal properties in municipal
      wastewater effluent.
AB  - Many fish use steroid hormones as pheromones to initiate behavioral and
      physiological changes during spawning. To assess the occurrence of steroid
      hormones with pheromonal properties in the aquatic environment and to evaluate
      the possibility that municipal wastewater discharges contain compounds that could
      affect fish reproduction by interfering with pheromones, several estrogens,
      androgens, and progestins were quantified by gas chromatography/tandem mass
      spectroscopy in effluent samples from 12 municipal wastewater treatment plants.
      Samples also were analyzed from an engineered treatment wetland, three
      groundwater wells, and one reservoir. Estrogens (17beta-estradiol and estrone)
      were detected in wastewater effluent at maximum concentrations of 4 and 12 ng/L,
      respectively. Androgens (testosterone and androstenedione) were detected at
      concentrations as high as 6.1 and 4.5 ng/L, respectively, whereas the synthetic
      progestin medroxyprogesterone was detected at concentrations up to 15 ng/L. Data
      from an effluent-receiving engineered treatment wetland and shallow groundwater
      wells suggested that these compounds were not rapidly attenuated. The measured
      concentrations of steroids often exceeded olfactory detection thresholds at which
      fish detect these steroids, and in several cases, the steroid concentrations were
      comparable to levels at which pheromonal responses have been observed in fish.

PMID- 14587902
TI  - Effects of surfactants on the dechlorination of chlorinated ethenes.
AB  - The influence of surfactants on a perchloroethene (PCE) dechlorinating mixed
      culture was investigated in laboratory experiments. Surfactants (Steol CS-330,
      Aerosol MA 80-I, alpha olefin sulfonate 14 to 16, Neodol 25-7, Tween 80, alkyl
      polyglycoside, C16TAB [trimethylammonium bromide], and sodium dodecyl sulfate)
      were evaluated for their effects on the rate and extent of PCE reductive
      dechlorination and their potential biodegradation by the mixed culture. Limited,
      if any, surfactant biodegradation was observed for the surfactants tested, and
      all surfactants impaired dechlorination in either the rate of PCE dechlorination
      or the terminal dechlorination products observed. Based on initial testing, a
      nonionic surfactant, Tween 80, and an anionic surfactant, Steol CS-330, were
      selected for additional investigation. Dechlorination of PCE to dichloroethene
      (DCE), vinyl chloride (VC), and ethene (ETH) occurred in all Tween 80-amended
      microcosms, with a depressed rate of ETH production as the only adverse effect.
      Steol CS-330, however, inhibited dechlorination beyond DCE at all surfactant
      concentrations exceeding 25 mg/L. Attempts to acclimate a culture to Steol CS-330
      were unsuccessful. Inhibition of VC and ETH production was reversible on dilution
      of the surfactant to a concentration of 10 mg/L or less, indicating that
      surfactant interactions with the enzyme system responsible for reductive
      dechlorination of DCE may be the cause of inhibition.

PMID- 14587903
TI  - Binding of perfluorinated fatty acids to serum proteins.
AB  - Perfluorooctane sulfonic acid (PFOS) accumulates in the liver and blood of
      exposed organisms. The potential for these surfactant molecules to interfere with
      hormone/protein interactions in blood is of concern given the importance of these
      interactions. The PFOS binding to serum proteins was investigated by assessing
      its ability to displace a variety of steroid hormones from specific binding
      proteins in the serum of birds and fishes. Perfluorooctane sulfonic acid had only
      a weak ability to displace estrogen or testosterone from carp serum steroid
      binding proteins. Displacement of cortisone in avian sera occurred at relatively
      low PFOS concentrations. Corticosterone displacement potency increased with chain
      length, and sulfonic acids were more potent than carboxylic acids. The PFOS
      concentrations estimated to cause these effects were 320 microM or greater,
      equivalent to serum concentrations greater than 160 mg/L. Using mass spectrometry
      and direct in vitro binding assays, PFOS was demonstrated to bind strongly to
      bovine serum albumin (BSA) in a 1:1 stoichiometric ratio. It appears that PFOS in
      serum is in general bound to albumins. Concentrations of PFOS required to
      saturate albumin would be in excess of 50 to 100 mg/L. Based on current
      environmental concentrations, it is unlikely that PFOS would cause displacement
      of hormones from serum proteins in wildlife.

PMID- 14587904
TI  - Hydroxylated and methylsulfone-containing metabolites of polychlorinated
      biphenyls in the plasma and blubber of bowhead whales (Balaena mysticetus).
AB  - Bowhead whale (Balaena mysticetus) blubber (n = 20) and plasma (n = 19) samples
      were collected during the 1997 to 2000 Inuit subsistence harvests in Barrow,
      Alaska, USA, to quantify the concentrations of methylsulfone (MeSO2)-containing
      and hydroxylated (OH) polychlorinated biphenyl (PCB) metabolites in this
      cetacean. The distribution of MeSO2-PCBs in blubber was dominated by 4-MeSO2
      substituted congeners, the most abundant being 4-MeSO2-CB-70, 3'-MeSO2-CB-132,
      and 4-MeSO2-CB-64. Mean (+/- 1 standard error) sum (sigma) MeSO2-PCBs
      concentrations in blubber were low (6.23 +/- 0.81 ng g(-1) lipid normalized)
      compared to concentrations previously reported in other marine mammals. However,
      similar ratios of MeSO2-PCB metabolites to parent PCB congeners among marine
      mammals suggest that cytochrome P450 2B-like biotransformation and other
      necessary enzyme-mediated processes and mechanisms that influence the formation
      and clearance of MeSO2-PCBs exist in the bowhead whale. Pentachlorophenol was the
      most abundant halogenated phenolic compound quantified in bowhead plasma (1.55 +/
      0.19 ng g(-1) wet wt). Despite indirect evidence for arene epoxidation of the
      biphenyl moiety inferred from MeSO2-PCB formation, sumOH-PCB concentrations in
      bowhead plasma were low (1.52 +/- 0.31 ng g(-1) wet wt) compared to humans and
      marine mammals and were comprised of only two detectable OH-PCB congeners (4'-OH
      CB-130 and 4-OH-CB-187). Further research is required to elucidate the
      toxicokinetics and distribution of OH-PCBs in this cetacean.

PMID- 14587905
TI  - Extraction of spiked metals from contaminated coastal sediments: a comparison of
      different methods.
AB  - Various extraction methods have been developed to assess metal bioavailability
      from sediments. In this study, we compared the extraction of Cd, Cr, and Zn from
      contaminated sediments using different extractants (normal seawater, acidic
      seawater of pH = 5. seawater with 1% sodium dodecyl sulfate [SDS], and gut
      digestive fluids collected in vitro from deposit-feeding peanut worm Sipunculus
      nudus) coupled with concurrent metal speciation measurements. The influences of
      sediment aging on metal extraction were also examined using radiotracer-spiked
      techniques. Sediments aging up to 100 d did not significantly affect the
      partitioning of spiked Cd and Cr in different geochemical phases, but the spiked
      Zn was partitioned more into the reducible fraction and less into the carbonate
      phase with increasing sediment aging. There was a major difference in the
      partitioning into different geochemical phases between the spiked metals and the
      native metals within the 100-d sediment aging. The difference between the spiked
      and native Cd and Zn extraction using gut juices was somewhat smaller than the
      strong geochemical contrast. Metals bound with the anoxic sediments were hardly
      extracted by different extractants. There was a significant relationship between
      the extraction of spiked Cd and its distribution in the exchangeable phase
      (positive correlation) or in the reducible phase (negative correlation). For Cr
      and Zn, extraction was not correlated with their partitioning in any of the
      geochemical phases. Further, extraction of all three metals by digestive gut
      fluids was not correlated with the concentrations of simultaneously extractable
      metals (SEM), nor with the difference between SEM and acid volatile sulfide
      (AVS). Our study suggests that there were large differences in extraction among
      metals using different extractants and only Cd extraction was significantly
      related to its geochemical speciation in sediments.

PMID- 14587906
TI  - Determination of the surface sorption properties of talc, different salts, and
      clay minerals at various relative humidities using adsorption data of a diverse
      set of organic vapors.
AB  - Adsorption constants of a diverse set of organic vapors have been measured on
      NaCl, KNO3, (NH4)2SO4, NH4Cl, kaolinite, bentonite. and talc at different
      relative humidities at 15 degrees C. Together with the earlier studied quartz
      (SiO2), CaCO3, and alpha-Al2O3, these surfaces represent relevant sorbents for
      organic vapors in the environment. An equation that describes the van der Waals
      and H-bond interactions between the sorbate and the surface can be used to
      describe the sorbate and sorbent variability in the measured data and to predict
      sorption constants of organic compounds that have not been tested on the
      respective surface. The unknown properties of the sorbent surfaces are used as
      fitting parameters in this equation. These data provide important insights into
      the variability of sorption properties of natural, inorganic surfaces as a
      function of relative humidity.

PMID- 14587907
TI  - Effect of pH and Release on two life stages of four anuran amphibians.
AB  - Using three native Canadian and one exotic anuran species, the interactive
      toxicity of pH and the forestry used-herbicide Release (triclopyr [3,5,6
      trichloro-2-pyridl-oxyacetic acid]) was assessed. Embryonic and larval (Gosner
      25) stages of Rana pipiens, Rana clamitans, Bufo americanus, and Xenopus laevis
      were exposed to treatments for at least 96 h in a static-renewal system using a
      central composite rotatable design. Mortality and the prevalence of malformations
      were modeled using generalized linear models with a profile deviance approach to
      obtain confidence intervals. Consistent trends of greater toxicity with lower pH
      were observed, with the majority of models (five of seven models) showing
      significant (p < 0.05) inverse relations. Larval lethal concentration estimates
      were eight to twenty-three times less than those observed for embryos, indicating
      that the larval stages were more sensitive to treatments. Further, the median
      lethal concentration (LC50) values for the larvae were below the expected
      environmental concentration (EEC) as calculated by Canadian regulatory
      authorities for Release. Species sensitivity was similar, with an average larval
      96-h LC50 of 0.89 mg acid equivalents (AE)/L at pH 5.5 and 1.6 mg AE/L at pH 7,
      suggesting that X. laevis is a reasonable surrogate for native amphibians in
      laboratory toxicity testing. For the embryo tests, R. pipiens were slightly less
      sensitive in comparison with the other three species. Based on a hazard quotient
      analysis (EEC/LC50 > 1) for the most sensitive larval life stages, higher tier
      ecotoxicological testing under more realistic environmental conditions is
      strongly recommended.

PMID- 14587908
TI  - Microcosm tributyltin bioaccumulation and multibiomarker assessment in the blue
      mussel Mytilus edulis.
AB  - Blue mussels, Mytilus edulis, were exposed to two different concentrations of
      tributyltin (TBT) in seawater, 1,000 ng Sn/L (C1 experiment) and 10 ng Sn/L (C2
      experiment), for 4 d, in order to evaluate the bioaccumulation of TBT by mussels
      Mytilus edulis in microcosms and to test the ability of a multimarkers analysis
      to determine the effects of TBT on the biochemical parameters in mussels. Tissue
      burdens of Mytilus edulis were 204 +/- 7 and 2,120 +/- 4 ng Sn/g TBT after the 4
      d tests for the C2 and C1 experiments, respectively. Analyses of dissected organs
      and/or tissues demonstrated that TBT accumulated to the greatest extent in gills
      in the C1 experiment and in the digestive gland in the C2 experiment.
      Bioconcentration factors (BCFs) were 12,100 +/- 300 and 2,000 +/- 10 for mussels
      exposed in the C2 and C1 experiments, respectively. The four biomarkers used in
      this work were acetylcholinesterase (AChE), glutathione S-transferase (GST),
      catalase (CAT) activities, and thiobarbituric acid-reactive substances (TBARS)
      contents. No significant changes were observed in the measured enzyme activities
      or in TBARS concentration after the 4-d TBT exposure.

PMID- 14587909
TI  - Developmental toxicity of in ovo exposure to polychlorinated biphenyls: II.
      Effects of maternal or paternal exposure on second-generation nestling american
      kestrels.
AB  - The development of second-generation nestling American kestrels (Falco
      sparverius) was altered by in ovo exposure of only one parent to polychlorinated
      biphenyls (PCBs). Polychlorinated biphenyls appear to alter nestling development
      through both maternally and paternally mediated effects. In 1998, F0 parent
      kestrels consumed approximately 5 to 7 microg total PCBs/g bird/d (Aroclors
      1248:1254: 1260) for approximately 100 d prior to eggs hatching; these eggs,
      containing total PCB concentrations of 34.1 microg/g, produced 13 F1 offspring,
      which were then paired in 1999 with unexposed kestrels to examine developmental
      effects of maternal or paternal in ovo PCB exposure. Using a toxicokinetics
      model, eggs from the maternally exposed group had predicted PCB levels of 0.03 to
      0.34 microg/g, with enriched higher chlorinated congeners. Polychlorinated
      biphenyl concentrations in eggs of all generations have recently been found in
      eggs and nestlings of free-ranging eagles. Consistent with the first generation,
      maternally exposed F2 females generally were larger, had altered growth rates,
      and delayed maximal growth and fledging compared with control females. Maternally
      exposed F2 males were heavier but had shorter bones, grew more quickly and
      earlier, and fledged 2 d later than control males. In the maternally exposed
      group, concentrations of plasma triiodothyronine were elevated in F2 females but
      suppressed in F2 males. Paternally exposed F2 hatchlings of both sexes were
      comparable in size to controls with the exception of having longer tarsi bones,
      but subsequently showed slower, delayed growth (both sexes) and fledging
      (females) and lower thyroxine concentrations (males). The alterations in thyroid
      hormones in the F2 generation are discussed in light of the enrichment of higher
      chlorinated PCB congeners and hydroxylated PCB congeners. The developmental
      changes in the kestrel nestlings are likely a function of several possible
      mechanisms involving maternal PCB deposition, parental behavior, and
      neurobehavioral and endocrine-thyroid function in nestlings.

PMID- 14587910
TI  - Effects of carbaryl on green frog (Rana clamitans) tadpoles: timing of exposure
      versus multiple exposures.
AB  - The majority of studies on pesticide impacts have evaluated the effects of single
      exposures. However, multiple exposures to a pesticide may be more prevalent. The
      objective of our study was to determine how multiple exposures versus single
      exposure at different times during development affected survival to
      metamorphosis, tadpole survival, tadpole mass, and tadpole developmental stage of
      green frog (Rana clamitans) tadpoles reared at low and high density in outdoor
      cattle tank ponds. Tadpoles were exposed to carbaryl zero, one, two, or three
      times at 14-d intervals. We applied single doses of carbaryl at one of three
      times, specifically during early, mid, or late development. Overall, we found
      that multiple exposures had a greater impact than single exposures during
      development. More individuals reached metamorphosis in ponds exposed to multiple
      doses of carbaryl compared with controls, indicating that the presence of
      carbaryl stimulated metamorphosis. The presence of carbaryl in the aquatic
      environment also resulted in more developed tadpoles compared with controls.
      Tadpoles in control ponds did not reach metamorphosis and were less developed
      than individuals exposed to carbaryl; this effect indicates that, under ideal
      conditions, green frogs could overwinter in ponds so that greater size could be
      attained before metamorphosis in the following spring or summer. Our study
      demonstrated the importance of including realistic application procedures when
      evaluating the effects of a pesticide and that multiple exposures to a short
      lived pesticide are more likely to affect an amphibian population.

PMID- 14587911
TI  - Reduced nicotinamide adenine dinucleotide phosphate and the higher incidence of
      pollution-induced liver cancer in female flounder.
AB  - In biological effect monitoring programs, induction of biotransformation and
      detoxification enzymes is used as a biomarker for pollution. Yet sex differences
      are usually neglected in the availability of reduction equivalents needed in
      these metabolic pathways and may affect biomarker responses. For example, female
      flounder have a threefold higher incidence of macroscopic liver nodules than
      males of the same age class in polluted environments of the North Sea that
      progress toward carcinomas, whereas tumors in males virtually never develop into
      cancer. Evidence is presented in this review that NADPH plays a significant role
      in this sex-related response to xenobiotics in liver of flounder. The NADPH is
      needed for biosynthesis, particularly of lipids and lipoproteins, and
      detoxification processes such as one-electron and two-electron biotransformation
      and conjugation and, therefore, its availability as substrate determines
      biomarker responses. Biotransformation of xenobiotics is more strongly induced
      and conjugation processes are less affected in male flounder liver during
      exposure. In female liver, NADPH is required for production of the yolk precursor
      protein vitellogenin for oocyte production. The latter process has a higher
      priority than the NADPH-requiring detoxification processes because reproductive
      success is more relevant in evolutionary perspectives than the survival of the
      individual female. The data reviewed here suggest that these sex-related
      differences in NADPH metabolism are a major cause of the higher incidence of
      liver cancer in female flounder in polluted environments.

PMID- 14587912
TI  - Factors influencing variability and potential uptake routes of heavy metals in
      black kites exposed to emissions from a solid-waste incinerator.
AB  - Exposure to heavy metals from emissions of the solid-waste incinerator (SWI) of
      Madrid (Spain) was assessed by determining the relationships between the distance
      from black kite (Milvus migrans) nests to the SWI and metal concentrations in
      nestling blood and failed eggs. Lead levels increased as the distance to the SWI
      decreased, while no significant relationship was found for the remaining
      elements. Analysis of frequency distributions showed that Pb was normally
      distributed, suggesting a generalized exposure to this contaminant. Variability
      in metal levels within and between nests indicated a differential nest exposure
      to contaminant metals with sibling chicks showing similar metal levels.
      Correlations between essential and contaminant metals suggested detoxifying
      mechanisms mediated by essential metals. The contribution of metal residues in
      blood coming from deposition in eggs was minimal compared with residues coming
      from posthatch exposure. Exposure to particulate volatile Pb in the form of dust
      from fly ash emitted to the air by the SWI is suggested to be the main route of
      uptake via inhalation, while both dietary and respiratory routes may contribute
      to Cd uptake. The increasing human population living close to the SWI may be
      increasingly at risk from exposure to air-borne contaminants depending on the
      emission standards from the SWI.

PMID- 14587913
TI  - Evaluation of polychlorinated biphenyl bioaccumulation patterns in white sea
      urchins (Lytechinus pictus) using multiple approaches.
AB  - The bioaccumulation of polychlorinated biphenyls (PCBs) from three amended field
      contaminated sediments (with total PCB concentrations of approximately 4, 10, and
      100 microg/g dry wt) by white sea urchins (Lytechinus pictus) was evaluated using
      multiple statistical and theoretical approaches. Similarity analysis of the PCB
      bioaccumulation patterns, based on the concept of ecological communities, showed
      that the PCB patterns in the sea urchins and source sediments were essentially
      identical for all three sediment concentrations. However, affinity analysis did
      show some preference for bioaccumulation of higher-molecular-weight and more
      hydrophobic congeners by the urchins. The affinity analysis also showed that
      within a homologous series, bioaccumulation increased with increasing
      hydrophobicity. The biota-sediment accumulation factor (BSAF) profiles for the
      two lower concentration sediments (A and B) were found to be statistically
      different from the high concentration sample (sediment C) by a multivariate
      analysis of variance (MANOVA). The relationship between the measured apparent
      organic carbon-normalized partition coefficients (K(OC)) and octanol-water
      partition coefficient (K(OW)) (log based) suggested a significant departure from
      thermodynamic equilibrium. A nonequilibrium, steady-state bioaccumulation model
      was found to correctly predict the observed experimental bioaccumulation
      patterns. To improve the model performance, a hydrophobic term was introduced to
      account for the drop-off in BSAF profiles with log K(OW) > or = 6.5. This study
      showed that nonequilibrium, steady-state models are far superior to equilibrium
      partitioning-based models for understanding the bioaccumulation of organic
      chemicals by sea urchins.

PMID- 14587914
TI  - Effects of 4-nonylphenol on phytoplankton and periphyton in aquatic microcosms.
AB  - The effects of nonylphenol (NP) on phytoplankton and periphyton were studied in
      230 L outdoor microcosms. Phytoplankton cell density and biomass, phytoplankton
      and periphyton diversity, and assemblage composition were analyzed during a four
      week preapplication period, followed by six weeks of NP treatment via controlled
      release and a six weeks postapplication period. Changes in species richness and
      diversity were not correlated with NP concentrations. However, changes in
      phytoplankton cell densities during the first week of the postapplication period
      were related to previous exposure. In the controls and the lowest-dosed
      microcosm. Conjugatophyceae constituted most of the biomass during the dosing and
      the postapplication period. In contrast, Dinophyceae dominated the biomass during
      the dosing and the postapplication period at higher NP concentrations. Principal
      response curves revealed changes in phytoplankton assemblage composition during
      the dosing and the postapplication period. Dinophyceae and most Cyanophyceae were
      more abundant at intermediate and higher NP concentrations, whereas
      Conjugatophyceae were less abundant compared to controls. Assemblages only partly
      recovered during the postapplication period. Periphyton taxon richness,
      diversity, and assemblage change was not related to NP concentrations. At the
      lowest and intermediate concentration, assemblages were significantly different
      from the controls and the higher concentrations, which were similar during the
      treatment period.

PMID- 14587915
TI  - Effects of nonylphenol on zooplankton in aquatic microcosms.
AB  - We investigated the effects of the endocrine disruptor nonylphenol (NP) on the
      zooplankton assemblages of 230 L aquatic microcosms during a four-week
      preapplication period, a six-week NP treatment via controlled release, and a six
      week postapplication period. Zooplankton assemblage change, investigated by
      ordination principal response curves (PRC), was due to lower abundances of
      copepoda, rotifera, and cladocera. The most sensitive groups/taxa were copepoda
      larvae, followed by the rotifers Synchaeta spp., Polyarthra spp., and the
      cladocerans Daphnia longispina and Chydorus sphaericus. The mean no-observed
      effect concentrations for the community (NOEC(community)) was 30 microg/L.
      Cladocera densities recovered during the postapplication period at all but the
      highest NP concentrations (maximum 120 microg/L); copepod densities did not
      recover at the three highest concentrations (maximum 96-120 microg/L).

PMID- 14587916
TI  - Response of the zooplankton community and environmental fate of perfluorooctane
      sulfonic acid in aquatic microcosms.
AB  - Little is known regarding perfluorooctane sulfonic acid (PFOS) toxicity to
      freshwater organisms. This field evaluation aims to assess the toxicological risk
      associated with exposure to PFOS across levels of biological organization. The
      analysis of variance study was conducted in replicate (n = 3) 12,000 L outdoor
      microcosms. Multivariate techniques were used to assess the response of
      zooplankton community structure and dynamics, as well as a floating macrophyte,
      Lemna gibba. The zooplankton community was significantly affected (p < 0.05) by
      the treatment regime given by the Monte Carlo permutations for all sampling
      times. A community-level no-observable-effect concentration ([NOEC]community) of
      3.0 mg/L was determined for the 35-day study, however, longer term studies are
      recommended. The most sensitive taxonomic groups, Cladocera and Copepoda, were
      virtually eliminated in 30 mg/L treatments after 7 d. The 42-d 50% inhibition
      concentration (IC50) for L. gibba frond number was 19.1 mg/L and the NOEC was 0.2
      mg/L. Furthermore, we investigated the persistence of PFOS over 285 d in
      microcosms under natural conditions. Perfluorooctane sulfonic acid concentration
      showed no drastic reduction in any treatment microcosm over the entire study
      period, confirming that this compound undergoes little degradation in aquatic
      systems. Presently, there appears to be little hazard to these freshwater
      organisms at reported environmental concentrations.

PMID- 14587917
TI  - Influence of dissolved organic matter source on silver toxicity to Pimephales
      promelas.
AB  - In the environment, the formation of organic and inorganic silver complexes can
      decrease Ag bioavailability (toxicity) to aquatic organisms. However, current
      water quality regulations do not consider the protective effects of water quality
      parameters such as dissolved organic carbon (DOC) concentration. To determine the
      effect of DOC concentration and source on silver toxicity, nine different natural
      organic matter isolates were used in 96-h static-renewal toxicity tests with
      fathead minnow (Pimephales promelas). The 96-h dissolved silver median lethal
      concentrations (LC50) among different sources of dissolved organic matter varied
      by up to fivefold (4.5-23.3 microg/L). Further, toxicity tests with organic
      matter from the site with the lowest 96-h LC50 value suggested only limited
      additional attenuation of silver toxicity when DOC concentration was increased
      from 5.1 to 14.0 mg/L. With this site excluded, we found little more than a
      twofold difference among 96-h dissolved Ag LC50s for the remaining sources (10.1
      23.3 microg/L). However, significant toxicological differences among sites
      remained. It was apparent that organic matter from different sources varied both
      chemically and toxicologically, but no conclusions could be drawn that related
      compositional variation to observed Ag toxicity for these isolates.

PMID- 14587918
TI  - Photoactivated toxicity in amphipods collected from polycyclic aromatic
      hydrocarbon-contaminated sites.
AB  - The risk of photoactivated PAH toxicity in contaminated aquatic systems has not
      been well characterized. To document risk, amphipods (Gammarus spp.) were
      collected from two polycyclic aromatic hydrocarbon (PAH)-contaminated sites in
      the lower St. Louis River and Duluth Harbor, USA (Hog Island and USX) as well as
      a reference site (Chipmunk Cove) and were exposed in two separate, replicate
      tests to controlled intensities of solar radiation for 3 d. Contaminated site
      organisms died significantly faster compared to control site organisms. In all
      tests, mortality was strongly related to ultraviolet-A (UV-A; 320-400 nm) dose.
      Ultraviolet-B (280-320 nm) radiation did not increase mortality. To compare
      susceptibility among populations, regressions of arcsine-transformed,
      proportionate mortality versus UV dose were completed for each, and the slopes
      were statistically compared. Response slopes for the two contaminated site
      populations were both significantly greater than the reference site population (p
      = 0.0001 for test 1; p = 0.0002 for test 2). These results indicate that
      organisms residing in PAH-contaminated environments can accumulate PAH
      concentrations sufficient to be at risk for photoactivated toxicity. Although
      amphipods are not typically at risk of PAH-photoactivated toxicity because they
      are largely protected from exposure to sunlight, they are representative
      surrogates for species that may be similarly protected at some life stages (and
      thus able to accumulate significant PAH tissue concentrations) but not at others.

PMID- 14587919
TI  - Effect of low salinity on cadmium accumulation and calcium homeostasis in the
      shore crab (Carcinus maenas) at fixed free Cd2+ concentrations.
AB  - Increased Cd toxicity at low salinity has been attributed to increased free Cd2+
      ion concentration ([Cd2+]sw), but transfer to dilute seawater also stimulates
      physiological ionic regulation in crabs. In this study, Cd accumulation and Ca
      homeostasis in the shore crab (Carcinus maenas) were explored at fixed [Cd2+]sw
      to reveal the physiological events during sublethal Cd exposure. Crabs were
      exposed to 3.4 or 34 microg/L [Cd2+], in both 100% seawater (SW) and 33% SW for
      up to 10 d and sampled for hemolymph composition as well as gill and
      hepatopancreas Ca, Cd, and Ca-ATPase activity. Cadmium exposure ameliorated the
      expected fall in hemolymph osmotic pressure and NaCl at low salinity and
      generally protected tissue Ca from decline. Cadmium exposure alone (within
      salinity) inhibited Ca-ATPase, but this was offset by stimulation of Ca-ATPase at
      low salinity. The Ca-ATPase activity in the anterior and posterior gills showed
      different responses to Cd/low salinity stress. Crabs were more sensitive to a 10
      fold increase in [Cd2+]sw at low salinity. Overall, we conclude that exposure to
      a fixed sublethal [Cd2+]sw reveals a compensatory physiological response that is
      driven primarily by salinity rather than Cd2+ free ion concentration.
      Physiological responses are therefore important during low-level Cd exposure in
      dilute seawater.

PMID- 14587921
TI  - Using reproductive endpoints in small forage fish species to evaluate the effects
      of Athabasca Oil Sands activities.
AB  - The main objective of this study was to evaluate the influence of naturally
      occurring oil sands-related compounds (OSRC) on reproductive function in fish in
      order to assess the impacts of anthropogenic point-source inputs. The health of
      slimy sculpin (Cottus cognatus) and pearl dace (Semotilus margarita) collected
      from the Alberta Athabasca Oil Sands (Canada) watershed were examined. Two rivers
      were selected for study: the Steepbank and the Ells. These rivers originate
      outside the oil sands formation, where fish are unexposed (Ref), exposed to
      naturally occurring oil sands-related compounds (Nat), or exposed to naturally
      occurring compounds as well as adjacent to surface mining activity (Dev).
      Assessment endpoints included gonadosomatic indices (GSI), fecundity, and in
      vitro gonadal steroid production. In vitro gonadal incubations demonstrated lower
      levels of steroid production at sites along the Steepbank River within the oil
      sands deposit. Hepatic 7-ethoxyresorufin-O-deethylase (EROD) activity, an
      indicator of exposure to OSRC, was elevated twofold at the site with natural
      compounds and up to 10-fold at the site adjacent to development compared to EROD
      activity in fish from the reference site. Fish collected in the Ells River had a
      threefold induction in EROD activity but no significant reduction in steroid
      production when compared to reference fish. No consistent alterations in gonadal
      development were seen in fish collected from sites within the oil sands deposit.
      This research in the Athabasca River basin provides baseline information of the
      health of fish populations within the oil sands deposit prior to further
      development in the area.

PMID- 14587920
TI  - Comparison of the sensitivity of three nematode species to copper and their
      utility in aquatic and soil toxicity tests.
AB  - Nematodes are useful organisms for aquatic and soil toxicity testing because of
      their abundance and diversity as well as their ease of culturing and maintenance
      in the laboratory. The nematode Caenorhabditis elegans has been used extensively
      in toxicity testing, but its sensitivity to metal exposures in relation to other
      nematodes remains unclear. In this study, we compare the sensitivity and ease of
      use of two other rhabditid nematodes, Panagrellus redivivus and Pristionchus
      pacificus, to C. elegans. Toxicity endpoints were chosen to investigate the
      effects of Cu on the survival of these nematodes after soil exposures and on the
      survival, reproduction, movement, and feeding behavior of nematodes after
      exposures in aquatic medium. In all lethality testing, P. pacificus was the most
      sensitive, C. elegans exhibited intermediate sensitivity, and P. redivivus was
      the least sensitive. Reproduction and movement of C. elegans and reproduction of
      P. pacificus were decreased 50% by similar concentrations of Cu (EC50s
      approximately 2 mg/L), but P. pacificus movement was less sensitive to Cu
      exposures (EC50 = 8 mg/L). Although all nematodes may be useful in lethality
      assays, using P. redivivus in toxicity tests is complicated by the presence of
      two sexes and difficulties in obtaining age-synchronized cultures. Pristionchus
      pacificus is an ideal acute toxicity-testing organism because of its sensitivity
      and ease of culturing. However, C. elegans appears to be more sensitive and
      therefore most useful in behavioral assays. Future studies of the relative
      sensitivities of nematodes in toxicity testing should continue to investigate
      additional toxicants, nematode species, and quantifications of sublethal effects
      after soil exposures.

PMID- 14587922
TI  - Productivity of American robins exposed to polychlorinated biphenyls, Housatonic
      River, Massachusetts, USA.
AB  - American robins (Turdus migratorius) breeding in the Housatonic River (MA, USA)
      watershed were studied in the field in 2001 to determine whether productivity was
      adversely affected by exposure to polychlorinated biphenyls (PCBs), as would be
      suggested by extrapolation from laboratory studies on other avian species. The
      study involved identifying nests within the Housatonic River floodplain (target
      area) and in reference areas beyond foraging distance of the floodplain,
      monitoring clutch size and number hatched and fledged, collecting eggs and
      nestlings for analysis for PCBs, and testing for differences in productivity
      between populations. One hundred and six active robin nests were monitored.
      Although concentrations of PCBs in target specimens were more than two orders of
      magnitude greater than in reference specimens, the only statistically significant
      differences in productivity were inconsistent with an exposure-related effect.
      First-generation productivity of exposed robins was within the range of natural
      background variation. Bioequivalence tests confirmed that first-generation
      productivity was statistically and biologically equivalent in target and
      reference robins. These findings contrast with extrapolations from laboratory
      studies of other avian species.

PMID- 14587923
TI  - Polychlorinated biphenyls and organochlorine pesticides in Baltic and Atlantic
      gray seal (Halichoerus grypus) pups.
AB  - Organochlorine pollutants (OCs), such as polychlorinated biphenyls (PCBs), DDT,
      chlordanes (CHLs), hexachlorobenzene (HCB) and hexachlorocyclohexanes (HCHs) were
      determined in blubber biopsies from free-ranging Baltic and Atlantic gray seal
      (Halichoerus grypus) pups. Well-fed pups from the Baltic Sea had concentrations
      of DDT, PCBs, and HCHs that were 2 to 10 times higher than in corresponding pups
      from populations in the Atlantic Ocean. The OC pattern in the Baltic seals
      differed significantly from that of their Atlantic relatives, reflecting the
      predominance of regional point source inputs into the Baltic Sea and long-range
      atmospheric inputs into the Atlantic Ocean. The differences in the pattern of the
      compounds also indicated an enhanced metabolism of the more metabolizable
      compounds in the more contaminated Baltic seals. Surprisingly, the proportions of
      the high chlorinated and low-volatile PCB congeners (> 6 Cl atoms) were
      comparable or lower in the Baltic pups as compared to the Atlantic pups. This
      difference might be due to Baltic seals occupying a lower trophic level than
      Atlantic seals and/or to the eutrophication situation in the Baltic Sea, which
      causes sedimentation of these PCB congeners. Significantly higher OC
      concentrations were found in starved and/or abandoned Baltic pups as compared to
      well-fed pups. The most contaminated Baltic seal pups in the present study had
      PCB concentrations that are comparable or higher than those reported to impair
      the immune systems and vitamin A dynamics in phocids.

PMID- 14587924
TI  - Association mechanisms of Europium(III) and Curium(III) with Chlorella vulgaris.
AB  - The association of Europium(III) (Eu[III]) and Curium(III) (Cm[III]) with
      Chlorella vulgaris and with cellulose was studied by a batch method and time
      resolved laser-induced fluorescence spectroscopy (TRLFS). The kinetics study
      performed by the batch method showed that maximum adsorption of Eu(III) and
      Cm(III) on C. vulgaris was attained within 3 min of contact; afterward, the
      percentage adsorption decreased with time due to chelation of the ions with
      exudates released from C. vulgaris with a strong affinity for Eu(III) and
      Cm(III). The TRLFS revealed that the short-term adsorption of Eu(III) on C.
      vulgaris was attributable to its coordination with cellulose on the algal cell
      wall. However, Eu(III) coordinated with the functional groups of cellulose very
      weakly despite the large distribution coefficients observed. These results
      indicate that the reactions, both at the cell's surfaces through adsorption and
      in solution phases through chelation with the exudates, are important in
      estimating the behavior of Eu(III) and Cm(III) in aqueous environments.

PMID- 14587925
TI  - Temperature influences on water permeability and chlorpyrifos uptake in aquatic
      insects with differing respiratory strategies.
AB  - Aquatic insects have evolved diverse respiratory strategies that range from
      breathing atmospheric air to breathing dissolved oxygen. These strategies result
      in vast morphological differences among taxa in terms of exchange epithelial
      surface areas that are in direct contact with the surrounding water that, in
      turn, affect physiological processes. This paper examines the effects of acute
      temperature shifts on water permeability and chlorpyrifos uptake in aquatic
      insects with different respiratory strategies. While considerable differences
      existed in water permeability among the species tested, acute temperature shifts
      raised water influx rates similarly in air-breathing and gill-bearing taxa. This
      contrasts significantly with temperature-shift effects on chlorpyrifos uptake.
      Temperature shifts of 4.5 degrees C increased 14C-chlorpyrifos accumulation rates
      in the gill-bearing mayfly Cinygma sp. and in the air-breathing hemipteran Sigara
      washingtonensis. However, the temperature-induced increase in 14C-chlorpyrifos
      uptake after 8 h of exposure was 2.75-fold higher in Cinygma than in Sigara.
      Uptake of 14C-chlorpyrifos was uniformly higher in Cinygma than in Sigara in all
      experiments. These findings suggest that organisms with relatively large exchange
      epithelial surface areas are potentially more vulnerable to both osmoregulatory
      distress as well as contaminant accumulation. Temperature increases appear more
      likely to impact organisms that have relatively large exchange epithelial surface
      areas, both as an individual stressor and in combination with additional
      stressors such as contaminants.

PMID- 14587926
TI  - Multivariate relationships between groundwater chemistry and toxicity in an urban
      aquifer.
AB  - Multivariate statistical methods were used to investigate the causes of toxicity
      and controls on groundwater chemistry from 274 boreholes in an urban area
      (London) of the United Kingdom. The groundwater was alkaline to neutral, and
      chemistry was dominated by calcium, sodium, and sulfate. Contaminants included
      fuels, solvents, and organic compounds derived from landfill material. The
      presence of organic material in the aquifer caused decreases in dissolved oxygen,
      sulfate and nitrate concentrations, and increases in ferrous iron and ammoniacal
      nitrogen concentrations. Pearson correlations between toxicity results and the
      concentration of individual analytes indicated that concentrations of ammoniacal
      nitrogen, dissolved oxygen, ferrous iron, and hydrocarbons were important where
      present. However, principal component and regression analysis suggested no
      significant correlation between toxicity and chemistry over the whole area.
      Multidimensional scaling was used to investigate differences in sites caused by
      historical use, landfill gas status, or position within the sample area.
      Significant differences were observed between sites with different historical
      land use and those with different gas status. Examination of the principal
      component matrix revealed that these differences are related to changes in the
      importance of reduced chemical species.

PMID- 14587927
TI  - The relationship of bioaccumulative chemicals in water and sediment to residues
      in fish: a visualization approach.
AB  - A visualization approach is developed and presented for depicting and
      interpreting bioaccumulation relationships and data (i.e., bioaccumulation
      factors [BAFs], biota-sediment accumulation factors [BSAFs], and chemical
      residues in fish) using water-sediment chemical concentration XY plots. The
      approach is based on five basic parameters that affect bioaccumulation of
      nonionic organic chemicals: The distribution of chemical between sediment and
      water, the hydrophobicity of the compound (expressed as the n-octanol/water
      partition coefficient, K(OW)), the relationship of food chains to water and
      sediment, the length of the food chains, and the degree to which the chemical is
      metabolized. The visualization approach using water-sediment XY plots captures
      and visually presents the existing bioaccumulation knowledge in a form that is
      readily understandable from chemical, biological, and ecological aspects and,
      therefore, useful in the assessment, communication, and management of risk for
      persistent bioaccumulative toxicants.

PMID- 14587928
TI  - Assessment of occupational exposure to human immunodeficiency virus and hepatitis
      C virus in a referral hospital in Burundi, Central Africa.

PMID- 14587929
TI  - Building better programs to prevent transmission of blood-borne pathogens to
      healthcare personnel: progress in the workplace, but still no end in sight.

PMID- 14587930
TI  - Surveillance for surgical-site infections: it's getting better all the time.

PMID- 14587931
TI  - Antiretroviral drug resistance in human immunodeficiency virus-infected source
      patients for occupational exposures to healthcare workers.
AB  - OBJECTIVE: To assess the prevalence of HIV antiretroviral resistance among source
      patients for occupational HIV exposures. DESIGN: Blood and data (eg, stage of
      HIV, previous antiretroviral drug therapy, and HIV RNA viral load) were collected
      from HIV-infected patients who were source patients for occupational exposures.
      SETTING: Seven tertiary-care medical centers in five U.S. cities (San Diego,
      California; Miami, Florida; Boston, Massachusetts; Albany, New York; and New
      York, New York [three sites]) during 1998 to 1999. PARTICIPANTS: Sixty-four HIV
      infected patients who were source patients for occupational exposures. RESULTS:
      Virus from 50 patients was sequenced; virus from 14 patients with an undetectable
      (ie, < 400 RNA copies/mL) viral load could not be sequenced. Overall, 19 (38%) of
      the 50 patients had primary genotypic mutations associated with resistance to
      reverse transcriptase or protease inhibitors. Eighteen of the 19 viruses with
      primary mutations and 13 wild type viruses were phenotyped by recombinant assays;
      19 had phenotypic resistance to at least one antiretroviral agent. Of the 50
      source patients studied, 26 had taken antiretroviral agents in the 3 months
      before the occupational exposure incident. Sixteen (62%) of the 26 drug-treated
      patients had virus that was phenotypically resistant to at least one drug. Four
      (17%) of 23 untreated patients had phenotypically resistant virus. No episodes of
      HIV transmission were observed among the exposed HCWs. CONCLUSIONS: There was a
      high prevalence of drug-resistant HIV among source patients for occupational HIV
      exposures. Healthcare providers should use the drug treatment information of
      source patients when making decisions about post-exposure prophylaxis.

PMID- 14587932
TI  - Differences in percutaneous injury patterns in a multi-hospital system.
AB  - OBJECTIVE: Determine differences in patterns of percutaneous injuries (PIs) in
      different types of hospitals. DESIGN: Case series of injuries occurring from 1997
      to 2001. SETTING: Large midwestern healthcare system with a consolidated
      occupational health database from 9 hospitals, including rural and urban,
      community and teaching (1 pediatric, 1 adult) facilities, ranging from 113 to
      1,400 beds. PARTICIPANTS: Healthcare workers injured between 1997 and 2001.
      RESULTS: Annual injury rates for all hospitals decreased during the study period
      from 21 to 16.5/100 beds (chi-square for trend = 22.7; P = .0001). Average annual
      injury rates were higher at larger hospitals (22.5 vs 9.5 PIs/100 beds; P =
      .0001). Among small hospitals, rural hospitals had higher rates than did urban
      hospitals (14.87 vs 8.02 PIs/100 beds; P = .0143). At small hospitals, an
      increased proportion of injuries occurred in the emergency department (13.7% vs
      8.6%; P = .0004), operating room (32.3% vs 25.4%; P = .0002), and ICU (12.3% vs
      9.4%; P = .0225), compared with large hospitals. Rural hospitals had higher
      injury rates in the radiology department (7.7% vs 2%; P = .0015) versus urban
      hospitals. Injuries at the teaching hospitals occurred more commonly on the wards
      (28.8% vs 24%; P = .0021) and in ICUs (11.4% vs 7.8%; P = .0006) than at
      community hospitals. Injuries involving butterfly needles were more common at
      pediatric versus adult hospitals (15.8% vs 6.5%; P = .0001). The prevalence of
      source patients infected with HIV and hepatitis C was higher at large hospitals.
      CONCLUSIONS: Significant differences exist in injury rates and patterns among
      different types of hospitals. These data can be used to target intervention
      strategies.

PMID- 14587933
TI  - Assessment of the compliance of Nigerian dentists with infection control: a
      preliminary study.
AB  - OBJECTIVE: To assess the compliance of a group of Nigerian dentists with standard
      infection control practices. METHOD: A confidential self-administered
      questionnaire survey was conducted among dentists engaged in active clinical
      practices in public hospitals in Lagos, Nigeria (n = 185). RESULTS: One hundred
      forty-six questionnaires were returned (response rate, 78.9%). Most (70.6%) of
      the dentists always wore gloves when treating patients, whereas 29.4% sometimes
      did. Regarding facemasks, 45.9% always wore them, 52.7% sometimes wore them, and
      1.4% never wore them. Protective eye wear was always worn by 4.8% of the
      dentists, sometimes worn by 52.7%, and never worn by 42.5%. Approximately half
      (50.7%) of the respondents had received hepatitis B vaccination. Sterilization
      was performed using a combination of methods, including autoclaving (84.1%),
      boiling (19.3%), dry heat (17.5%), and chemicals (29.7%). Nonavailability of
      materials was the major reason for noncompliance with infection control
      practices. CONCLUSIONS: Nigerian dentists need continuous education regarding
      infection control. Also, Nigerian hospitals urgently need adequate funding for up
      to-date and functional equipment and materials.

PMID- 14587934
TI  - Detection of postoperative surgical-site infections: comparison of health plan
      based surveillance with hospital-based programs.
AB  - BACKGROUND: Review of health plan administrative data has been shown to be more
      sensitive than other methods for identifying postdischarge surgical-site
      infections (SSIs), but there has not been a direct comparison between this method
      and hospital-based surveillance for all infections, including those diagnosed
      before discharge. We compared these two methods for identifying SSIs following
      coronary artery bypass graft (CABG) procedures. METHODS: We studied 1,352 CABG
      procedures performed among members of one health plan from March 1993 through
      June 1997. Health plan administrative records were reviewed based on claims
      containing diagnoses or procedures suggestive of infection or outpatient
      dispensing of antibiotics appropriate for SSI. Hospital-based surveillance
      information was also reviewed. SSI rates were calculated based on the total
      events identified by either mechanism. RESULTS: Postdischarge information was
      reviewed for 328 (85%) of 388 procedures. SSIs were confirmed in 167 patients
      (13% overall risk of confirmed SSI; range, 3% to 14% in the 5 hospitals). The
      overall sensitivity of hospital-based surveillance was 49.7% (83 of 167), and
      that of health plan data was 71.8% (120 of 167). There was no significant
      difference among hospitals in the sensitivity of either surveillance mechanism.
      CONCLUSIONS: Surveillance based on health plan data identified more postoperative
      infections, including those occurring before discharge, than did hospital-based
      surveillance. Screening administrative data and pharmacy activity may be an
      important adjunct to SSI surveillance, allowing efficient comparison of hospital
      specific rates. Interpretation of differences among hospitals' infection rates
      requires case mix adjustment and understanding of variations in hospitals'
      discharge diagnosis coding practices.

PMID- 14587935
TI  - Standardized infection ratios for three general surgery procedures: a comparison
      between Spanish hospitals and U.S. centers participating in the National
      Nosocomial Infections Surveillance System.
AB  - OBJECTIVES: To compare Spanish surgical wound infection (SWI) rates for three
      procedures with those published by the U.S. NNIS System, and to analyze quarterly
      trends. DESIGN: This was a 4-year prospective analysis of SWI using data from a
      Spanish nosocomial infection surveillance network based on CDC classification
      criteria. SWI rates were computed as standardized infection ratios (SIRs). Trends
      for both SWIs and SIRs were evaluated by linear regression. SETTING: Forty-three
      Spanish hospitals during 1997 through 2000. PATIENTS: Those undergoing
      cholecystectomy (n = 7,631), appendectomy (n = 5,780), and herniorrhaphy (n =
      9,864). RESULTS: For cholecystectomy patients, the SWI rate was 4.38% and the SIR
      was 3.32. Both of these variables showed a slightly rising, although
      nonsignificant, linear trend during the study period. For appendectomy patients,
      the SWI rate was 7.94% and the SIR was 2.86. The linear trend was increasing for
      both, but only the SWI rate attained significance. For herniorrhaphy patients,
      the SWI rate was 1.77% and the SIR was 1.64. Both of these variables showed a
      significant descending tendency during the 4 years. CONCLUSIONS: Because the SIR
      takes into account the patient risk category, it is the best indicator of the
      trend shown by the SWI rate over time for a given surgical procedure. According
      to our comparison of SIRs with reference NNIS System values, SWI rates for
      cholecystectomy and appendectomy were high. Monitoring of the SIR will provide a
      basis for the design of infection control measures and the assessment of their
      effectiveness.

PMID- 14587936
TI  - Pseudomonas surgical-site infections linked to a healthcare worker with
      onychomycosis.
AB  - OBJECTIVE: To determine the etiology of Pseudomonas aeruginosa surgical-site
      infections following cardiac surgery. SETTING: University teaching hospital.
      PATIENTS: Those with wound cultures that grew P. aeruginosa after cardiac surgery
      performed from 1999 to 2001. METHODS: Medical records and operating room (OR)
      records of patients with P. aeruginosa cardiac surgical-site infections from 1999
      to 2001 were reviewed. Healthcare workers involved with two or more cases were
      interviewed and examined. Specimens for environmental cultures were obtained from
      the ORs and cardiac surgical equipment. Cardiac surgery cases were observed and
      postoperative care and the cleaning of surgical instruments were investigated. OR
      air handling system records during the epidemic period were reviewed. Molecular
      fingerprinting of available P. aeruginosa isolates from infected patients and a
      healthcare worker was done. RESULTS: There were five P. aeruginosa cardiac
      surgical-site infections from January to August 2001, compared with no such
      infections from 1999 to 2000. All were adult patients. One cardiac surgeon with
      onychomycosis operated on all five cases. He did not routinely double glove. The
      involved fingernail grew P. aeruginosa. Three P. aeruginosa patient isolates were
      available for pulsed-field gel electrophoresis; two were identical to the isolate
      from the involved surgeon's onychomycotic nail. No environmental OR cultures grew
      P. aeruginosa. The surgeon's culture-positive nail was completely removed. There
      have been no P. aeruginosa surgical-site infections among cardiac surgery
      patients since this intervention. CONCLUSION: At least two cases of a cluster of
      P. aeruginosa surgical-site infections resulted from colonization of a cardiac
      surgeon's onychomycotic nail.

PMID- 14587937
TI  - Prolonged candidemia in infants following surgery for congenital heart disease.
AB  - OBJECTIVES: To describe a group of infants with complex congenital heart disease
      (CCHD) who had candidemia postoperatively and to perform a case-control study of
      risk factors. DESIGN: Descriptive and case-control study. SETTING: Tertiary-care
      medical centers. PATIENTS: Infants with CCHD who underwent cardiac surgery and
      developed candidemia. Controls were matched for congenital heart disease lesions,
      age, and postoperative hospital stay. RESULTS: Of 95 infants younger than 6
      months with CCHD who underwent cardiac surgery between January 1999 and April
      2001, 6 (6.3%) developed candidemia with 5 different species. The candidemia was
      prolonged (range, 12 to 32 days; median, 17 days). The interval between cardiac
      surgery and onset of candidemia was 12 to 57 days (median, 24 days). All had a
      central venous catheter inserted 8 to 50 days prior to the onset of candidemia.
      The mortality rate was 83%, compared with 13% for the group without candidemia. A
      univariate analysis of the potential risk factors revealed that duration of total
      parenteral nutrition (TPN), duration of antibiotics, intraoperative
      cardiopulmonary bypass time, and documentation of an intravascular thrombus were
      associated with candidemia. In multivariate analysis, long duration of TPN and
      documentation of a thrombus were associated with candidemia. CONCLUSIONS:
      Candidemia following cardiac surgery for infants with CCHD was persistent and
      associated with high mortality. The variety of species indicates that this was
      not a common-source outbreak. Risk factors associated with candidemia were
      duration of TPN and documentation of an intravascular thrombus.

PMID- 14587938
TI  - A national survey of surgical antibiotic prophylaxis in Turkey.
AB  - OBJECTIVE: To assess the quality of antibiotic prophylaxis for clean and clean
      contaminated elective surgical procedures. DESIGN: A cross-sectional, country
      wide survey. SETTING: Thirty-six hospitals in 12 cities in Turkey. PARTICIPANTS:
      Four hundred thirty-nine surgeons from 6 different specialties who performed
      selected procedures of interest. METHODS: A random sample of surgeons from
      different hospitals was selected. A standardized data collection form was used to
      record the type of procedure, the names, doses, timing of the first doses, and
      duration of antibiotics, important decisive factors, and problems in the
      management of prophylactic antibiotic use for surgical procedures. RESULTS: Fifty
      five percent of surgeons addressed completed the survey. For clean-contaminated
      procedures, 6% of surgeons did not use antibiotic prophylaxis, whereas 88% used
      more than a single dose. Inappropriate antibiotics were chosen for 32% of
      procedures. In 39% of procedures, the first dose of antibiotics was not
      administered during induction of anesthesia. Duration of prophylaxis was longer
      than 24 hours in 80% and longer than 48 hours in 46% of all procedures. Only 112
      surgeons (26%) were using definitely appropriate prophylaxis in all ways.
      Multivariate analysis revealed that surgeons in university hospitals (OR, 2.353;
      CI95, 1.426-3.884; P = .001) and general surgeons (OR, 4.986; CI95, 2.890-8.604;
      P < .001) used antibiotic prophylaxis more appropriately. Patients not covered by
      health insurance (OR, 0.417; CI95 0.225-0.772; P < .001) were associated with
      inappropriate prophylaxis. CONCLUSION: Given the high frequency of antibiotics
      prescribed for surgical prophylaxis in Turkey, adherence to surgical prophylaxis
      guidelines is urgently needed.

PMID- 14587939
TI  - Antimicrobial activity of glucoprotamin: a clinical study of a new disinfectant
      for instruments.
AB  - OBJECTIVE: To determine the in vitro efficacy of glucoprotamin for the
      disinfection of instruments. DESIGN: Prospective observational study. SETTING:
      University women's hospital. METHODS: Instruments were immersed in saline
      solution after use, and glucoprotamin was added to a concentration of 1.5% before
      soaking for 60 minutes. Biocidal activity was determined by the difference in
      colony-forming units (CFU) on instruments before and after disinfection. RESULTS:
      One hundred thirty-seven instruments were collected during 10 days and exposed to
      a 1.5% dilution of glucoprotamin without prior washing. Bioburden before
      disinfection ranged from 2 x 10(5) to 7.1 x 10(7) CFU per instrument. Average
      bacterial killing was 5.98 log10 CFU +/- 0.48 under aerobic conditions and 6.75
      log10 CFU +/- 0.54 under anaerobic conditions, despite the presence of large
      amounts of proteins on instruments that were frequently bloody. No vegetative
      bacteria were isolated in any sample after disinfection. CONCLUSION: This
      clinical study confirmed excellent in vitro efficacy of glucoprotamin without
      prior removal of proteins and debris.

PMID- 14587940
TI  - Activity of three disinfectants and acidified nitrite against Clostridium
      difficile spores.
AB  - OBJECTIVE: To identify environmentally safe, rapidly acting agents for killing
      spores of Clostridium difficile in the hospital environment. DESIGN: Three
      classic disinfectants (2% glutaraldehyde, 1.6% peracetyl ions, and 70%
      isopropanol) and acidified nitrite were compared for activity against C.
      difficile spores. Four strains of C. difficile belonging to different serogroups
      were tested using a dilution-neutralization method according to preliminary
      European Standard prEN 14347. For peracetyl ions and acidified nitrite, the
      subjective cleaning effect and the sporicidal activity was also tested in the
      presence of organic load. RESULTS: Peracetyl ions were highly sporicidal and
      yielded a minimum 4 log10 reduction of germinating spores already at short
      exposure times, independent of organic load conditions. Isopropanol 70% showed
      low or no inactivation at all exposure times, whereas glutaraldehyde and
      acidified nitrite each resulted in an increasing inactivation factor (IF) over
      time, from an IF greater than 1.4 at 5 minutes of exposure time to greater than
      4.1 at 30 minutes. Soiling conditions did not influence the effect of acidified
      nitrite. There was no difference in the IF among the 4 strains tested for any of
      the investigated agents. Acidified nitrite demonstrated a good subjective
      cleaning effect and peracetyl ions demonstrated a satisfactory effect.
      CONCLUSIONS: Cidal activity was shown against C. difficile spores by
      glutaraldehyde, peracetyl ions, and acidified nitrite. As acidified nitrite and
      peracetyl ions are considered to be environmentally safe chemicals, these agents
      seem well suited for the disinfection of C. difficile spores in the hospital
      environment.

PMID- 14587941
TI  - Nonmagical tools.

PMID- 14587942
TI  - Theoretical risk for occupational blood-borne infections in forensic
      pathologists.
AB  - Using a cumulative probability analysis and published data, we calculated the
      theoretical career risk of occupational HIV (2.4%) and HCV (39%; possible range,
      13% to 94%) infections for forensic pathologists. Serologic studies of these
      physicians are needed to clarify occupational exposure and infection risks.
      Autopsy personnel should wear cut-resistant undergloves to decrease percutaneous
      injuries.

PMID- 14587943
TI  - Ten-year persistence of antibody to hepatitis B surface antigen in healthcare
      workers vaccinated against hepatitis B virus, and response to booster
      vaccination.
AB  - This study estimated the number of HCWs with protective antibody levels 5 and 10
      years after HBV vaccination. Kaplan-Meier probabilities of protective levels were
      0.95 at 60 days after vaccination, 0.87 at 5 years, and 0.79 at 10 years. Those
      without protective levels displayed good response 7 and 30 days after a booster.

PMID- 14587944
TI  - Elevated preoperative fasting serum glucose levels increase the risk of
      postoperative mediastinitis in patients undergoing open heart surgery.
AB  - We conducted a case-control study to investigate the relationship between
      preoperative fasting serum glucose and postoperative mediastinitis in patients
      undergoing open heart surgery. Multivariate analysis revealed that a glucose
      level of 126 mg/dL or greater was associated with a significantly increased risk
      of mediastinitis (OR, 5.25; P = .002).

PMID- 14587945
TI  - Effectiveness of gentamicin-impregnated cement in the prevention of deep wound
      infection after primary total knee arthroplasty.
AB  - Effectiveness of gentamicin-impregnated cement in preventing deep wound infection
      after total knee arthroplasty (TKA) was estimated using data from prospective
      surveillance. In multivariate analysis, the protective effect of gentamicin
      impregnated cement on the development of infection was close to the limit of
      significance. Gentamicin-impregnated cement may prevent TKA infections.

PMID- 14587946
TI  - Meningitis due to Enterobacter aerogenes subsequent to resection of acoustic
      neuroma and percutaneous endoscopic gastrostomy tube placement: a rare nosocomial
      event.
AB  - We present a case of meningitis after percutaneous endoscopic gastrostomy (PEG)
      tube placement subsequent to acoustic neuroma resection and cranioplasty. Four
      days following PEG tube placement, the patient developed Enterobacter aerogenes
      meningitis, requiring explantation of infected cranioplasty material. His
      condition subsequently improved. Etiology and future intervention strategies are
      discussed.

PMID- 14587947
TI  - Light-activated antimicrobial coating for the continuous disinfection of
      surfaces.
AB  - The ability of a photosensitizer-containing cellulose acetate film to kill
      bacteria was evaluated. Substantial kills were achieved following irradiation of
      the film with white light for up to 24 hours. Applying a photosensitizer
      containing coating to surfaces could reduce the environmental load of pathogens,
      thus helping to prevent infectious disease transmission.

PMID- 14587948
TI  - Biocides currently used for bronchoscope decontamination are poorly effective
      against free-living amoebae.
AB  - Free-living amoebae may be pathogenic and harbor several agents of pneumonia. We
      tested the susceptibility of amoebal cysts and trophozoites to currently used
      biocides for bronchoscope decontamination. We showed that two particular biocides
      are inadequate for disinfecting bronchoscopes, as Acanthamoeba polyphaga survived
      3 hours of exposure to these undiluted agents.

PMID- 14587949
TI  - Outbreaks of community-associated methicillin-resistant Staphylococcus aureus
      skin infections.

PMID- 14587950
TI  - Comparison of Dalmatian water evaluation indices.
AB  - Water quality in the Dalmatian waters of Southern Croatia was assessed using four
      different indices: an arithmetic index, arithmetic modified index, geometric
      modified index, and Solway-modified index. The waters were sampled 12 times
      during 1 year (from July 1998 to July 1999) at 50 sampling sites in Dalmatia.
      Nine water quality parameters were evaluated: temperature, mineralization,
      corrosion coefficient, dissolved oxygen, biochemical oxygen demand, total
      nitrogen, protein nitrogen, total phosphorus, and total coliform. A comparison of
      the indices showed that the arithmetic modified index and Solway modified index
      are relatively similar for high-quality water (i.e., they enable better
      discrimination between high- and low-quality water). Both indices, however, tend
      to yield a lower index number for low-quality waters.

PMID- 14587951
TI  - Maintaining granulation in a denitrifying upflow sludge-blanket reactor treating
      groundwater with low hardness.
AB  - Maintenance of denitrifying granular sludge for treating soft groundwater (total
      hardness = 75 mg calcium carbonate/L) in an upflow sludge-blanket reactor was
      demonstrated with complete removal of applied nitrate (20 mg N/L) over extended
      operation and a hydraulic residence time of 34 minutes. A high pH of
      approximately 9.0 was shown to be important for generation of mineral
      precipitation needed for production of heavy granular sludge with good retention
      characteristics. As a method of increasing precipitation potential, pH adjustment
      was determined to be more economically favorable than calcium or alkalinity
      supplementation. In addition, temporary increases in substrate loading were shown
      to be effective for enhancing biomass levels in a manageable granular sludge. The
      significance of biomass in promoting mineral precipitation was discussed.

PMID- 14587952
TI  - Evaluation of constructed wetland treatment performance for winery wastewater.
AB  - Rapid expansion of wineries in rural California during the past three decades has
      created contamination problems related to winery wastewater treatment and
      disposal; however, little information is available about performance of on-site
      treatment systems. Here, the project objective was to determine full-scale,
      subsurface-flow constructed wetland retention times and treatment performance
      through assessment of water quality by daily sampling of total dissolved solids,
      pH, total suspended solids, chemical oxygen demand (COD), tannins, nitrate,
      ammonium, total Kjeldahl nitrogen, phosphate, sulfate, and sulfide across
      operating systems for winery wastewater treatment. Measurements were conducted
      during both the fall crush season of heavy loading and the spring following
      bottling and racking operations at the winery. Simple decay model coefficients
      for these constituents as well as COD and tannin removal efficiencies from winery
      wastewater in bench-scale reactors are also determined. The bench-scale study
      used upward-flow, inoculated attached-growth (pea-gravel substrate) reactors fed
      synthetic winery wastewater. Inlet and outlet tracer studies for determination of
      actual retention times were essential to analyses of treatment performance from
      an operational subsurface-flow constructed wetland that had been overloaded due
      to failure to install a pretreatment system for suspended solids removal. Less
      intensive sampling conducted at a smaller operational winery wastewater
      constructed wetland that had used pretreatment suspended solids removal and
      aeration indicated that the constructed wetlands were capable of complete organic
      load removal from the winery wastewater.

PMID- 14587953
TI  - Pilot-scale evaluation of separate-stage nitrification using an attached-growth,
      moving-bed media process.
AB  - Submerged attached-growth processes, both fixed and moving bed, are becoming more
      popular. These processes may or may not be used in combination with suspended
      growth treatment. The objective of this project was to evaluate a tertiary
      attached-growth, moving-bed media nitrification system based on the ammonia
      nitrogen removal rates and effluent concentrations that could be achieved. A
      pilot-scale system for nitrification of secondary municipal wastewater effluent
      was operated for 142 days. The minimum aeration requirements for media mixing
      provided sufficient dissolved oxygen. The generation of biological solids from
      nitrification was insignificant. Design effluent ammonia-nitrogen concentrations
      (<6 mg/L) were achieved at influent loading rates greater than design (1.18 g
      ammonia-nitrogen/[m2 x d]) coincident with detention times shorter than design
      conditions (4 hours). Empirical relationships for the ammonia-nitrogen removal
      rate and effluent concentration as a function of influent ammonia-nitrogen
      loading were developed. Detention time is believed to be an important parameter
      affecting these relationships.

PMID- 14587954
TI  - Effects of oxygen on anoxic biodegradation of benzoate during continuous culture.
AB  - In this study, various amounts of oxygen were added to denitrifying chemostats
      receiving benzoate to mimic the input of oxygen to anoxic zones of biological
      nutrient removal systems. The effect of oxygen on the biodegradative capability
      of the mixed-microbial culture for benzoate was investigated. The anoxic benzoate
      biodegradative capability of the culture was not significantly changed as the
      mass flowrate of oxygen was increased to 40% of the input benzoate chemical
      oxygen demand (COD) mass flowrate, but was decreased approximately 70% when the
      mass flowrate of oxygen was increased to 70% of the input benzoate COD mass
      flowrate. The decrease in the anoxic benzoate biodegradative capability was due
      primarily to the loss of the denitrifying enzymes (measured by the anoxic
      pyruvate-degrading ability) and not to the loss of the key anoxic catabolic
      enzyme (benzoyl-coenzyme A reductase). The proportional increase in the
      concentration of nitrate as the residual terminal electron acceptor and the lack
      of synthesis of aerobic ring-cleavage enzymes as the oxygen input to the
      chemostat was increased suggest that the mixed microbial culture preferred oxygen
      to nitrate as the terminal electron acceptor, but degraded benzoate using the
      anoxic metabolic pathway. The concentration of the mixed microbial culture
      increased as the oxygen input to the chemostat was increased, suggesting that the
      oxygen was used by cytochrome cbb3 rather than quinol oxidase because the
      energetic yield of cytochrome cbb3 is higher than that of quinol oxidase or the
      nitrogen oxide reductases.

PMID- 14587955
TI  - Odor and volatile organic compound removal from wastewater treatment plant
      headworks ventilation air using a biofilter.
AB  - Laboratory-scale experiments and field studies were performed to evaluate the
      feasibility of biofilters for sequential removal of hydrogen sulfide and volatile
      organic compounds (VOCs) from wastewater treatment plant waste air. The biofilter
      was designed for spatially separated removal of pollutants to mitigate the
      effects of acid production resulting from hydrogen sulfide oxidation. The inlet
      section of the upflow units was designated for hydrogen sulfide removal and the
      second section was designated for VOC removal. Complete removal of hydrogen
      sulfide (H2S) and methyl tert-butyl ether (MTBE) was accomplished at loading
      rates of 8.3 g H2S/(m3 x h) (15-second empty bed retention time [EBRT]) and 33 g
      MTBE/(m3 x h) (60-second EBRT), respectively. In field studies performed at the
      Hyperion Treatment Plant in Los Angeles, California, excellent removal of
      hydrogen sulfide, moderate removal of nonchlorinated VOCs such as toluene and
      benzene, and poor removal of chlorinated VOCs were observed in treating the
      headworks waste air. During spiking experiments on the headworks waste air, the
      percentage removals were similar to the unspiked removals when nonchlorinated
      VOCs were spiked; however, feeding high concentrations of chlorinated VOCs
      reduced the removal percentages for all VOCs. Thus, biofilters offer a distinct
      advantage over chemical scrubbers currently used at publicly owned treatment
      works in that they not only remove odor and hydrogen sulfide efficiently at low
      cost, but also reduce overall toxicity by partially removing VOCs and avoiding
      the use of hazardous chemicals.

PMID- 14587956
TI  - Flow and transport simulation models for prediction of chlorine contact tank flow
      through curves.
AB  - Turbulent flow, solute transport, and chemical and biological decay are some of
      the basic processes encountered in water treatment plants. This paper presents
      recent developments in the numerical simulation of turbulent flow and
      disinfection processes in disinfection contact tanks. Simulation runs have been
      conducted for various tank design alternatives and in different grid resolutions.
      The accuracy of simulated contact tank flow and the disinfection process depends
      largely on calculations of the hydrodynamic and solute transport characteristics
      in the tanks. A key factor of this is the accuracy of advection and shear stress
      term computations, which can be affected by the use of different hydrodynamic
      submodels and numerical schemes. The performance of a simulation model relies to
      a great extent on the right combination of such submodels and numerical schemes.
      In this study, a number of simulation models were tested against realistic tank
      configurations and measurements to evaluate the various combinations of
      turbulence models and difference schemes by analyzing predicted flow and solute
      transport patterns, as well as the corresponding flow-through curves. Models for
      disinfection tank simulations are recommended based on comparisons of simulation
      results with measurements. These models may also be applied to other water
      treatment processes such as wastewater treatment.

PMID- 14587957
TI  - Kinetic study of the hydrodechlorination of trichloroethene in water using a
      platinum catalyst and hydrazine.
AB  - Column experiments were used to measure the hydrodechlorination rate of
      relatively high concentrations of trichloroethene (TCE) (approximately 100 mg L(
      1)). Trichloroethene in water was treated with a platinum on titania (Pt-TiO2)
      catalyst and hydrazine. The influence of some experimental conditions (i.e.,
      flowrate, temperature, and pH) on the catalytic conversion of TCE was studied.
      The pseudo-first-order rate constant of the overall hydrodechlorination of TCE
      was approximately 1 x 10(-3) to 1 x 10(-2) s(-1) in the temperature range of 283
      to 328 K and was determined from the dependence of the TCE conversion on the
      contact time of the feed water with the catalyst by assuming first-order
      kinetics. The activation energy of the catalytic hydrodechlorination of TCE was
      calculated as approximately 34 kJ/mol from the temperature dependence of the rate
      constant. The TCE conversion increases with increasing pH, and probably
      correlates with the presence of un-ionized hydrazine.

PMID- 14587959
TI  - Evidence-based medicine and information mastery: application for acute
      gastrointestinal conditions.
AB  - Although advances in medical therapeutics are providing more options to improve
      patient care, the medical professional, wading through information overload, may
      not be effective in critically evaluating new data and making informed decisions
      based on them. Evidence-based medicine and information mastery offer clear
      guidelines to help health care professionals critically evaluate the relevance
      and validity of articles as they relate to patient care. When evaluating
      literature it is important to emphasize patient-oriented evidence that matters,
      rather than disease-oriented evidence.

PMID- 14587958
TI  - History of acid suppression: focus on the hospital setting.
AB  - In the hospital setting, prophylactic acid suppression is an important part of
      care for many critically ill patients. It may also prevent rebleeding in patients
      admitted with acute upper gastrointestinal tract bleeding. Effective treatments
      for these conditions stemmed from our increased understanding of the gastric acid
      secretory pathway and target pH values. The late 1970s saw the introduction of
      histamine2-receptor antagonists (H2RAs), which partially suppress basal and meal
      stimulated acid secretion. Some of these agents can induce an intragastric pH
      greater than 3, lasting for approximately 10 hours/day when given twice/day at
      recommended doses. This level of acid suppression can facilitate healing of
      duodenal ulcers but has limited efficacy for other indications (e.g.,
      gastrointestinal bleed). In the late 1980s a more potent class of acid
      suppressing agents was developed, proton pump inhibitors (PPIs). The PPIs can
      induce an intragastric pH above 3 lasting for approximately 17 hours/day, and an
      intragastric pH above 5 for approximately 9 hours/day after once-daily oral
      administration of recommended doses. It is possible to attain even higher target
      pH values with large doses and with continuous intravenous infusion. Thus, PPIs
      are agents of choice for treatment of many acid-related disorders including
      peptic ulcer disease and moderate-to-severe gastroesophageal reflux disease, and
      for prevention of rebleeding in patients with upper gastrointestinal bleeding.
      Availability of an intravenous formulation, pantoprazole, enables hospitalized
      patients for whom oral administration is not feasible to benefit from the
      superior potency of PPIs. Preliminary data suggest that intravenous PPIs may be
      more effective than H2RA prophylaxis against stress-related ulcer bleeding for
      intensive care patients and should facilitate healing in those with bleeding
      ulcers of the upper gastrointestinal tract.

PMID- 14587960
TI  - Physiology of the parietal cell and therapeutic implications.
AB  - The field of acid suppression has been advanced by therapeutics of increasing
      specificity for inhibiting gastric acid secretion. Particularly important are
      proton pump inhibitors (PPIs), which inhibit the activity of the gastric acid
      pump (H+,K(+)-adenosine triphosphatase), the final common step in gastric acid
      production. Histamine2-receptor antagonists, which act at an early stage of the
      acid secretion pathway, are less effective and are subject to intolerance. The
      PPIs are weak bases that undergo accumulation in the acidic space of the
      secreting parietal cell and are converted in acid to the active thiophilic form,
      which then forms disulfide bonds with key cysteines of the gastric acid pump.
      Pantoprazole differs from other PPIs in terms of its reaction with cysteine 822
      in the pump and with cysteine 813, a common binding site for all PPIs. Both
      cysteines are in the sixth transmembrane segment, which is part of the ion
      transport pathway. This selective binding may have an impact on the dwell time of
      pantoprazole versus other PPIs because it is inaccessible to reducing agents, in
      contrast to cysteine 813. Pantoprazole is also very stable (has a slow rate of
      activation) at neutral pH values compared with other PPIs and has a relatively
      robust plasma concentration-time curve. These agents are important in the
      management of duodenal ulcers, nonsteroidal antiinflammatory drug-induced ulcers,
      gastroesophageal reflux disease, and dyspepsia, but basic pharmacokinetic and
      pharmacodynamic differences among them may affect clinical utility.

PMID- 14587961
TI  - Pharmacologic properties of proton pump inhibitors.
AB  - Since their introduction into clinical practice in the 1980s, proton pump
      inhibitors (PPIs) have proved to be of enormous value in the management of acid
      peptic disorders. They have become the treatment of choice for most, if not all,
      acid-related gastrointestinal disorders, including gastroesophageal reflux
      disease, peptic ulcer, and Zollinger-Ellison syndrome. With approval of an
      intravenous formulation, the benefits of PPIs are extended to critically ill
      patients for whom oral drug administration is often unsuitable. Five PPIs are
      approved for clinical use in the United States. Although they share a common core
      structure and mechanism of action, it is important to understand the general
      pharmacology of these agents and how they differ from histamine2-receptor
      antagonists in order to optimize PPI therapy.

PMID- 14587962
TI  - Treating patients with acute gastrointestinal bleeding or rebleeding.
AB  - Despite advances in medical management, gastrointestinal bleeding remains a
      substantial cause of morbidity and mortality. At risk are patients with history
      of the event, those taking nonsteroidal antiinflammatory agents, and those with
      active peptic ulcer disease. Endoscopy may be performed for diagnosis and
      treatment. Antisecretory therapy may be employed to control gastric acid
      secretion, treat active peptic ulcer disease, and control symptoms such as
      diarrhea and abdominal pain. Options for antisecretory therapy include histamine2
      receptor antagonists (H2RAs) that target the histamine pathway, and proton pump
      inhibitors (PPIs) that target the final step in acid secretion. The H2RAs
      generally are ineffective at reaching a target pH of 6 in patients with
      gastrointestinal bleeding because of tachyphylaxis. The PPIs are more effective
      and do not lead to tachyphylaxis. With the availability of an intravenous PPI,
      pantoprazole, options for managing hospitalized patients with gastrointestinal
      bleeding are expanding.

PMID- 14587963
TI  - Acid suppression in critically ill patients: what does the evidence support?
AB  - Stress-related mucosal disease is a frequent complication in critically ill
      patients. A wealth of evidence suggests that hypoperfusion to the upper
      gastrointestinal tract can lead to ulceration and is associated with increased
      morbidity. Management of stress ulcers depends on aggressive therapy that
      includes acid-suppressive agents. Proton pump inhibitors (PPIs) have gained
      recognition as a potentially important therapy for treatment and prevention of
      upper gastrointestinal bleeding in critically ill patients. Patients who present
      to the hospital with acute gastrointestinal bleeding benefit from potent acid
      inhibition. Whereas histamine2-receptor antagonists have questionable efficacy in
      preventing ulcer rebleeding in this patient population, PPIs are highly
      effective. They should be considered first-line therapy for patients undergoing
      endoscopic hemostasis and for those with stigmata of upper gastrointestinal
      bleeding.

PMID- 14587964
TI  - The cost of enhanced acid suppression.
AB  - Peptic ulcer disease (PUD), gastroesophageal reflux disease (GERD), and upper
      gastrointestinal bleeding are conditions that can make large demands on health
      care resources. Acid suppression is common therapy for these conditions. The
      economic implications of managing Helicobacter pylori-related PUD, GERD, and
      upper gastrointestinal bleeds were considered by several investigators. Economic
      analyses of drug regimens for PUD show that eradication is more cost effective
      than H2-receptor antagonist (H2RA) maintenance therapy. Although various
      eradication regimens have been compared, the results depend on a number of
      assumptions that preclude general conclusions regarding cost-effectiveness.
      Economic analyses related to GERD are hindered by the often chronic, relapsing
      nature of the disease, particularly once therapy is discontinued. Therefore, as
      with PUD, results of the economic analyses depend largely on initial assumptions
      relative to the model employed. With regard to upper gastrointestinal bleeding,
      proton pump inhibitors (PPIs) are potent acid suppressors that may help prevent
      rebleeding that was managed endoscopically. Further clinical and economic
      investigations of PPIs for stress ulcer prophylaxis are necessary. Cost
      effectiveness studies comparing PPIs and H2RAs should focus on overall costs of
      managing these conditions and include economic benefits of preventing
      complications, and not on drug-acquisition costs alone.

PMID- 14587966
TI  - Age differences in factor analysis of EEG.
AB  - This study examined age differences in the factor structure of EEG using a 128
      electrode system. Running EEG records were obtained from healthy younger and
      healthy older adults before, during, and after they performed a 13-minute
      Continuous Performance Task. Factor analyses were conducted on each five-second
      segment of EEG data by treating the voltages obtained at each electrode site as
      variables and each measurement epoch as a case. Results showed that the EEG
      records of older adults yielded significantly more factors than those of younger
      adults in every task condition. In addition, eigenvalues for the first common
      factor derived from EEG data sets were significantly larger in the EEG recordings
      of younger adults than older adults. The results are interpreted to indicate a
      greater degree of complexity in the spatial distribution of EEG activity in older
      adults, possibly reflecting an age-related decrease in the degree of coordination
      among cortical areas.

PMID- 14587965
TI  - Cortical control mechanisms in volitional swallowing: the Bereitschaftspotential.
AB  - OBJECTIVE: This research sought to identify a well-defined pre-motor potential,
      the Bereitschaftspotential (BP), as a manifestation of cortical contribution to
      the pre-motor planning of volitional swallowing. METHODS: EEG data were collected
      from 20 research participants during volitional execution of swallowing and
      finger movement tasks. A5 second pre-movement epoch for each task was triggered
      on EMG identification of movement onset. A grand average for each task
      representing approximately 2400 trials across all research participants was
      derived to compare and contrast morphological features of the derived waveform.
      RESULTS: Volitional pharyngeal swallowing and finger movement generated similar
      waveform characteristics of duration and slope; however, statistically
      significant differences were identified in polarity and in amplitude at four
      points both early and late in the epoch. Additionally, swallowing produced a pre
      motor waveform with a rapid declination of EEG activity in the final 500 msec
      prior to movement onset. CONCLUSIONS: This study demonstrates activation of the
      supplementary motor cortex preceding the onset of volitional swallowing. However,
      unlike purely voluntary movements, the volitional pharyngeal swallowing task, as
      assessed with this methodology, does not appear to recruit the primary motor
      cortex. Thus engagement of the swallowing response appears to rely on indirect
      parallel pathways between extrapyramidal cortical motor planning regions and
      lower motor neurons.

PMID- 14587967
TI  - Measurement of the conductivity of skull, temporarily removed during epilepsy
      surgery.
AB  - The conductivity of the human skull plays an important role in source
      localization of brain activity, because it is low as compared to other tissues in
      the head. The value usually taken for the conductivity of skull is questionable.
      In a carefully chosen procedure, in which sterility, a stable temperature, and
      relative humidity were guaranteed, we measured the (lumped, homogeneous)
      conductivity of the skull in five patients undergoing epilepsy surgery, using an
      extended four-point method. Twenty-eight current configurations were used, in
      each of which the potential due to an applied current was measured. A finite
      difference model, incorporating the geometry of the skull and the electrode
      locations, derived from CT data, was used to mimic the measurements. The
      conductivity values found were ranging from 32 mS/m to 80 mS/m, which is much
      higher than the values reported in other studies. Causes for these higher
      conductivity values are discussed.

PMID- 14587968
TI  - A model for frequency dependence of conductivities of the live human skull.
AB  - A mathematical model (sigma(omega) approximately equal to A omega alpha, where,
      sigma is identical with conductivity, omega = 2 pi f is identical with applied
      frequency (Hz), A (amplitude) and alpha (unit less) is identical with search
      parameters) was used to fit the frequency dependence of electrical conductivities
      of compact, spongiosum, and bulk layers of the live and, subsequently, dead human
      skull samples. The results indicate that the fit of this model to the
      experimental data is excellent. The ranges of values of A and alpha were,
      spongiform (12.0-36.5, 0.0083-0.0549), the top compact (5.02-7.76, -0.137
      0.0144), the lower compact (2.31-10.6, 0.0267-0.0452), and the bulk (7.46-10.6,
      0.0133-0.0239). The respective values A and alpha for the respective layers of
      the dead skull samples were (40.1-89.7, -0.0017-0.0287), (5.53-14.5, -0.0296 - 
      0.0061), (4.58-15.9, -0.0226-0.0268), and (12.7-25.3, -0.0158-0.0132).

PMID- 14587969
TI  - Magnelic stimulation can modulate seizures in epileptic patients.
AB  - OBJECTIVE: The aim of this study is to investigate the influence of external
      magnetic stimulation (EMS) in epileptic patients using magnetoencephalographic
      (MEG) measurements and non-linear analytic techniques. METHODS: The examined
      group consisted of 15 men aged 19-56 years (mean: 39.5 +/- 11.3) and 15 women
      aged 15-53 years (mean: 36.7 +/- 11.4). For each one the magnetic activity was
      recorded from 32 points for each temporal lobe. External magnetic stimulation
      (EMS) with proper field characteristics (intensity: 1-7.5 pT, frequency: the
      alpha-rhythm of the patient (8-13 Hz)) was applied in the frontal, occipital and
      temporal lobes for 2 to 6 minutes and the emitted brain magnetic activity was
      recorded again. In order to investigate if there is any alteration in the MEG
      complexity underlying the neural dynamics characterizing the pathologic brain
      before and after the EMS, chaotic analysis approach was applied for the
      estimation of the dimensional analysis of the existing strange attractors.
      RESULTS: The application of EMS resulted in rapid attenuation of the MEG activity
      of epileptic patients. The obtained results of the dimensionality calculation
      provide a shift from lower to higher dimensional values. Such a shift is an
      indication that we are dealing with a chaotic system similar with the one
      characterizing normal subjects. CONCLUSIONS: The increased values of the
      dimensional complexity and the lower activity of the MEG after the application of
      EMS strongly supports the beneficial effects of EMS in epileptic patients.

PMID- 14587970
TI  - Computation for the implicit components of ERP in attention.
AB  - EEG reveals brain functions with high temporal resolution. Yet, multiple implicit
      variables may be involved in limited ERP measures. Special computation techniques
      are needed to recover these parameters. In the study of attention, we can obtain
      the ERP in attended (V) and unattended (U) conditions. Usually, the effect of
      attention is computed as the difference (D) between V and U with the assumption
      that D and U are independent. Yet, they should be related. Treating V as a
      function of U, a linear model V = W + GU is assumed, where W and G are implicit
      in the ERP measures. G is the gain control on the unattended function. Provided G
      and W are constant over a local brain region, we can use the Total Least Square
      (TLS) algorithm to compute their values. In the experiment, participants attended
      to one side of a fixed point, and stimulus of circular checkerboard was flashed
      either to the attended or the unattended side. The values of W and G as functions
      of V and U were computed showing that multiple implicit variables are involved in
      attention. The gain amplification (G) is found to be greater than 1 before 200
      msec and much less than 1 afterwards. The values of G and W may shed light on the
      nature of attention.

PMID- 14587971
TI  - Management of benign vocal fold lesions: a survey of current opinion and
      practice.
AB  - Empirical data are often not available to guide clinical practices in the
      treatment of benign mucosal lesions of the vocal folds. The purpose of this
      report is to describe opinions and practices in order to identify areas of
      consensus and discrepancy and thus guide future inquiry. A 16-item survey mailed
      to all active US members of the American Academy of Otolaryngology-Head and Neck
      Surgery (n = 7,321) included questions on the use of voice therapy; diagnostic
      testing; perioperative use of steroids, antibiotics, and antireflux medications;
      and use of lasers. Responses used a Likert 5-point scale with end anchors of 1
      equaling "never" and 5 equaling "always" and were stratified according to lesion
      (nodules, polyps, cysts). A 16.5% response rate (n = 1,208) was obtained. A lack
      of consensus was most evident in the use of voice therapy for lesions other than
      nodules; antireflux medication; and intravenous steroids. Disagreement was also
      noted regarding the use of lasers, oral steroids, and antibiotics. Other than
      voice therapy as initial intervention for nodules, no statistically significant
      differences by lesion type exist regarding use of voice therapy, laser, or any
      medication. Prospective clinical trials addressing voice therapy, antireflux
      medications, steroids, and antibiotics are needed to inform clinical practice.
      Furthermore, treatment practices appear to be largely independent of lesion type.
      Therefore, traditional diagnostic categories do not seem to be useful guides to
      treatment, and may need to be reevaluated in light of improvements in diagnostic
      technology and surgical technique.

PMID- 14587972
TI  - Thyroarytenoid muscle responses to air pressure stimulation of the laryngeal
      mucosa in humans.
AB  - Others have observed glottic adduction in response to air puff stimuli and
      suggested that this is a reliable indicator of laryngeal sensation. We undertook
      to determine whether the same thresholds are found if one uses either
      thyroarytenoid (TA) muscle responses or subjects' reports of laryngeal sensation.
      We also studied the characteristics of TA responses to unilateral air pressure
      stimulation of the mucosa overlying the arytenoid cartilages. Ten normal
      volunteers provided button press responses to air pressure stimuli during
      bilateral TA electromyography. Similar thresholds were determined by reports of
      sensation as by electromyographic responses (p < .0005). The early TA responses
      occurred either around 80 ms or around 125 ms after onset of the air puff, with
      equal frequency on the ipsilateral and contralateral sides. The TA muscle
      responses to air pressure stimulation differ in physiological characteristics
      from the laryngeal adductor reflex that occurs in response to electrical
      stimulation of the superior laryngeal nerve.

PMID- 14587973
TI  - Hamartoma of the larynx: an unusual cause of dyspnea.
AB  - We present a rare case of cartilaginous hamartoma involving the subglottic larynx
      and presenting as respiratory distress. The symptoms were initially attributed to
      asthma; however, the clinical picture progressed to stridor with significant
      airway obstruction. After the airway was secured with a tracheostomy, the tumor
      was resected with a CO2 laser. We present relevant aspects of this benign airway
      condition and its surgical management.

PMID- 14587974
TI  - Hypopharyngeal pharyngoplasty in the management of pharyngeal paralysis: a new
      procedure.
AB  - Dysphagia after a high vagal nerve injury may be associated with a patulous
      hypopharynx that serves as a reservoir for pharyngeal secretions, contributing to
      primary or secondary aspiration. We describe a new hypopharyngeal pharyngoplasty
      procedure for the paralyzed pharynx to improve swallow. The paralyzed pyriform
      sinus is resected to remove insensate and redundant mucosa. The inferior
      constrictor muscle is then advanced anterior to the oblique line of the thyroid
      cartilage to improve pharyngeal tone and prevent pharyngeal dilatation. The
      surgery is performed in conjunction with medialization laryngoplasty and
      arytenoid adduction. The utility of this procedure is reviewed retrospectively in
      8 patients. They were evaluated by clinical evaluation, fiberoptic endoscopic
      evaluation of swallow, and modified barium swallow study. All had significant
      preoperative dysphagia. Three patients were gastrostomy tube-dependent. After
      operation, all patients had subjective and objective improvements in swallow and
      progressed to peroral feeding. There were no operative complications. We conclude
      that hypopharyngeal pharyngoplasty diminishes pyriform sinus pooling and improves
      pharyngeal transit. Dysphagia patients with unilateral pharyngeal paralysis
      secondary to cranial nerve palsies may benefit from this new procedure.

PMID- 14587975
TI  - Decannulation and survival following tracheostomy in an intensive care unit.
AB  - We investigated the long-term outcome of patients requiring tracheostomy in an
      intensive care unit (ICU) in an attempt to identify risk factors that would
      indicate a low probability of early decannulation. A retrospective study was
      conducted of a consecutive series of 106 patients who underwent tracheostomy in
      the period between January 1, 2001, and December 31, 2001, during their admission
      to the ICU at the Royal Melbourne Hospital, Melbourne, Australia. There were 61
      male and 39 female patients with a median age of 65 years. The indications for
      tracheostomy were prolonged mechanical ventilation (47), tracheobronchial toilet
      or risk of aspiration (45), and an unstable or obstructed airway (8). Thirty
      seven patients died during the study period. All surviving patients were
      successfully decannulated (median cannulation time, 25 days). Patients with
      tracheostomies inserted for an unstable or obstructed airway had a significantly
      shorter cannulation time (median time of 13 days) as compared to the other two
      indications (mechanical ventilation, 25 days; risk of aspiration, 33 days; log
      rank test, chi2(2) = 14.62 and p = .0007). Multivariate analysis showed that the
      effect of an unstable or obstructed airway was independent of the remaining group
      variables. We conclude that ICU patients who need a tracheostomy have a high
      mortality rate. Only the indication for tracheostomy insertion predicts early
      decannulation, and other patient variables are not significant predictors.

PMID- 14587976
TI  - Symptoms, quality of life, videolaryngoscopy, and twenty-four-hour triple-probe
      pH monitoring in patients with typical and extraesophageal reflux.
AB  - A prospective study was designed to characterize patients with typical and
      extraesophageal reflux (EER) symptoms and seek predictive patterns for each
      group. Fifteen subjects without symptoms, 16 patients with symptomatic
      gastroesophageal reflux disease (GERD), and 37 patients with symptomatic EER were
      evaluated with outcomes tools, videolaryngoscopy, and 24-hour triple-probe pH
      monitoring. Higher symptom scores, Voice Handicap Index scores, and
      Gastrointestinal Symptom Rating Scale scores, as well as similarly decreased
      quality of life as measured by the Short Form 36, were noted among the two
      symptomatic groups. Patients with clinically diagnosed EER were more likely to
      have multiple abnormalities on laryngoscopy. There was a trend toward more
      pharyngeal reflux episodes in EER patients (6.9 +/- 8.9) as compared to GERD
      patients (6.0 +/- 9) and asymptomatic subjects (1.1 +/- 1.9). On the basis of the
      pH monitoring of asymptomatic subjects, we define pathological pharyngeal reflux
      as more than 5 episodes in 24 hours. Pharyngeal acid exposure is more common in
      patients presumed to have EER, but some pharyngeal reflux does occur in
      asymptomatic subjects. Neither symptom scores nor videolaryngoscopic findings
      were predictive of pathological EER as indicated by pH monitoring.

PMID- 14587977
TI  - Laryngeal foreign bodies in children revisited.
AB  - To review our experience with inhaled laryngeal foreign bodies in children, we
      performed a retrospective review of all admissions to our institution between
      March 1989 and March 2002 with the diagnosis of an inhaled laryngeal foreign
      body. We included only cases in which the diagnosis was confirmed at endoscopy
      under general anesthesia. Two children were dead on arrival at our institution as
      a result of upper airway obstruction following a choking episode and did not
      undergo endoscopy; they were not included. Nine children (5 male, 4 female) were
      identified. The age range was 5 months to 13 years 9 months, although only 1
      child was older than 32 months. The foreign body was removed within 24 hours of a
      witnessed choking episode in 4 children, and the diagnosis was delayed in 5
      children for a period between 4 days and 2 months, including 2 in whom a history
      of a choking episode had been initially obtained. One complication occurred in a
      child in whom the diagnosis was delayed; he developed laryngeal edema after
      foreign body removal and required endotracheal intubation for 1 week.

PMID- 14587978
TI  - Tracheal resection with primary anastomosis in cadavers: the effects of releasing
      maneuvers and length of tracheal resection on tension.
AB  - To determine the relationships among length of trachea resected, total tracheal
      length, and anastomotic tension when using various release maneuvers, we studied
      10 adult human cadavers: 5 male and 5 female. The trachea was transected between
      rings 2 and 3. Precision, handheld spring tensiometers (Geneva Gage, LLC) were
      used to measure the tension required to approximate, and then overlap, the
      proximal segment relative to the distal segment, and the distal segment relative
      to the proximal segment after these maneuvers: no release, blunt dissection, neck
      flexion, suprahyoid release (SHR) without neck flexion, SHR with neck flexion,
      and right hilar release. After the tension measurements were recorded, the
      trachea was harvested and the total tracheal length was measured. Length-tension
      curves were plotted for both the superior and inferior tracheal segments after
      each release maneuver. The stiffness coefficient for the trachea and the resting
      load on the trachea following each release maneuver were calculated. An
      exponential length-tension relationship existed for the distal tracheal segment
      regardless of whether release maneuvers were performed. The proximal tracheal
      segment exhibited a linear length-tension relationship initially, but displayed
      an exponential relationship after SHR. We could resect 6.68 cm (range, 4.2 to 9.9
      cm), 13.3 rings (range, 10 to 20 rings), or 65.5% (range, 42% to 100%) of the
      trachea without undue tension (<1,000 g) on the anastomosis. We conclude that
      various tracheal release maneuvers are effective in increasing the length of
      trachea that can be relatively safely resected. However, these maneuvers are not
      uniformly effective across subjects.

PMID- 14587979
TI  - Tympanometry accurately measures middle ear underpressures in monkeys.
AB  - Tympanometry is useful for evaluating middle ear (ME) status, but its accuracy in
      estimating true ME pressure has been questioned. We evaluated the accuracy of
      tympanometry in 6 monkeys. Direct application and measurement of ME pressure were
      achieved with a probe introduced into the mastoid antrum, and tympanometry was
      done over a large range of applied ME pressures. For all ears, tympanometric
      pressure was a linear function of applied pressure. At large overpressures, the
      tympanometric pressure was approximately 40 mm H2O greater than the applied
      pressure, but there was little error in the measurement for applied
      underpressures. The measurement error was proportional to the ME pressure
      multiplied by the ratio of the extant volume displacement of the tympanic
      membrane to ME volume. These results show that in monkeys, tympanometry provides
      an accurate, relatively unbiased estimate of ME underpressure and suggest that
      the measurement error for tympanometry can be predicted for MEs of other species.

PMID- 14587980
TI  - Benign paroxysmal positional vertigo in older women may be related to
      osteoporosis and osteopenia.
AB  - Benign paroxysmal positional vertigo (BPPV), so-called canalolithiasis and
      cupulolithiasis, usually occurs after head trauma or viral vestibular neuritis.
      In many cases, the cause remains obscure, and it often affects women more than 50
      years old. The goal of this work was to study a possible relationship between
      BPPV and osteopenia or osteoporosis. Thirty-two women, whose ages ranged from 50
      to 85 years (median age, 69 years), who had BPPV and were free of any other
      otoneurologic history, were selected. The diagnosis of osteopenia or osteoporosis
      was confirmed by a bone mineral density measurement made with dual x-ray
      absorptiometry of spine and hip (T-score). The BPPV was unilateral in 26 patients
      and bilateral in 6 patients. Our results showed osteopenia or osteoporosis in 24
      of the 32 patients (75%) with BPPV. The T-scores were compared in 3 age groups to
      those of 83 healthy women. The patients with BPPV had a significantly lower (p <
      .026) T-score in all groups. Possible pathophysiological mechanisms are discussed
      to explain the apparent correlation between BPPV and osteopenia or osteoporosis.

PMID- 14587981
TI  - Intrasphenoidal transsellar encephalocele repaired by endoscopic approach.
AB  - Spontaneous sphenoidal encephaloceles are rare entities. In the case of
      intrasphenoidal encephaloceles, most defects are temporosphenoidal and occur in
      the lateral wall of the sphenoidal sinus. There have been to our knowledge only 7
      reports of medial, transsellar encephaloceles in the literature. We report a case
      of intrasphenoidal transsellar encephalocele that was successfully managed
      through an endoscopic approach with complementary lumboperitoneal shunting. This
      disorder presents a challenge in surgical management because of the involvement
      of opticochiasmatic structures, the hypothalamopituitary axis, and the delicate
      vasculature of the circle of Willis in and around the encephalocele, besides
      proximity to the cavernous sinus. Rhinologists should be aware of these
      malformations, since the optic nerve or chiasma may be totally exposed in the
      sphenoidal sinus in the course of this disease. This case illustrates the need
      for magnetic resonance imaging in case of sphenoidal abnormalities, as well as
      the possibility of endonasal repair without a transcranial approach for large
      intrasphenoidal encephaloceles.

PMID- 14587982
TI  - Histologic changes in human vocal folds correlated with aging: a
      histomorphometric study.
AB  - The voice of aged persons is usually different from that of younger adults--a
      fact indicating that aging induces changes in the human larynx. The aim of this
      study was to perform a histomorphometric analysis of the vocal fold and of a
      fragment of skin in order to determine the modifications related to aging and
      possible differences between genders. Twenty cadavers, 10 men and 10 women, were
      studied. Stereological methods were used for histologic analysis. In the vocal
      folds, we observed a reduction of the lamina propria thickness (p < .001) and of
      epithelial cell density (p < .001) as a function of age. In the skin, there was a
      reduction of chorion thickness (p = .02) and of epithelial cell density (p =
      .01). The decrease in the thickness of the lamina propria of the vocal folds with
      aging may contribute to the vocal pattern present in the elderly. These changes
      were more evident in men.

PMID- 14587983
TI  - Expression of nitric oxide synthases in nasal mucosa from a mouse model of
      allergic rhinitis.
AB  - Nitric oxide (NO), which is produced by nitric oxide synthase (NOS), has been
      recently identified as a multifunctional mediator. As for nasal tissue, however,
      the distribution and expression patterns of 3 isoforms of NOS, including neuronal
      NOS (nNOS, type I NOS), inducible NOS (iNOS, type II NOS), and endothelial NOS
      (eNOS, type III NOS), are still unclear. To evaluate the function of NO in the
      pathophysiology of nasal allergy, we investigated the distribution of NOSs in the
      nasal mucosa of C57BL/6 mice with allergic rhinitis to the house dust mite,
      Dermatophagoides farinae. Immunoreactivity to each isoform of NOS was
      immunohistochemically observed. In the allergic nasal mucosa, many eosinophils
      had infiltrated. Immunoreactivity to NOS types I and III was localized to the
      surface epithelial and vascular endothelial cells in both allergic and control
      groups without a statistically significant difference. In contrast, the type II
      NOS immunoreactivity was weak in normal mice and increased after allergic
      sensitization. The type II NOS expression of the surface epithelial and vascular
      endothelial cells was significantly elevated in the allergic group as compared
      with the control group. These findings suggest that a large amount of NO may be
      produced in the nasal mucosa of mice by type II NOS after allergic sensitization
      and that type II NOS may play an important role in the pathogenesis of allergic
      rhinitis.

PMID- 14587984
TI  - Radiotherapy of early-stage glottic cancer: analysis of factors affecting
      prognosis.
AB  - This study is a retrospective analysis of 134 patients treated with radiotherapy
      at our hospital. The sample included 88 stage T1 and 46 stage T2 patients. Sixty
      two patients had anterior commissure involvement, 37 patients had impaired vocal
      cord mobility, and 24 patients had supraglottic or subglottic extension.
      Irradiation was given, with the dose ranging from 60 to 72 Gy. Laryngectomy was
      the main salvage treatment for local recurrence. The 5-year initial and final
      local control rates were 71% and 83%, and the 10-year initial and final local
      control rates were 69% and 80%, comparable to the results of other series. The 5
      year rate of overall survival with final larynx preservation was 77%.
      Multivariate analysis revealed that anterior commissure involvement is prognostic
      of a poor outcome in patients with T1 glottic cancer. Further subgroup analysis
      revealed that a fraction size of > 200 cGy could overcome the negative impact of
      anterior commissure involvement and significantly improve the 5-year local
      control rate in T1 patients (100% at > 200 cGy versus 45% at < or = 200 cGy; p =
      .04). Subglottic extension of the glottic cancer predicted poor outcome in T2
      patients. The 5-year local control rates of patients with and without subglottic
      extension were 9% and 77%, respectively (p < .001). According to our results,
      radiotherapy with a fraction size of > 200 cGy is recommended for T1 disease with
      anterior commissure involvement. For patients with T2 disease and subglottic
      extension, radiotherapy alone produces poor results. Further improvement of
      outcomes by other treatment strategies needs to be investigated.

PMID- 14587985
TI  - Cheek mucocele occurring long after parotid duct transplantation for
      xerophthalmia.

PMID- 14587986
TI  - Helmet poster boy.

PMID- 14587987
TI  - Hallux rigidus: demographics, etiology, and radiographic assessment.
AB  - PURPOSE: The purpose of the study was to evaluate the demographics, etiology, and
      radiographic findings associated with hallux rigidus in patients treated
      surgically over a 19-year period in a single surgeon's practice. METHODS:
      Patients treated for hallux rigidus by cheilectomy and metatarsophalangeal joint
      fusion were identified from 1981 to 1999. Patients who had diabetes, inflammatory
      arthritis, infectious arthritis, crystalline arthritis, multiple forefoot
      deformities, neuromuscular disorders, or had died were excluded. A chart review
      and evaluation of preoperative radiographs were completed on all eligible
      patients. All identified patients were invited for a follow-up examination that
      included standard and stress radiographs, range-of-motion testing, Harris mat
      study, gait analysis, first ray mobility measurement, and standardized
      questionnaire assessment. RESULTS: One hundred ten of 114 (96.5%) patients with a
      diagnosis of hallux rigidus returned for the final evaluation. Eighty cheilectomy
      patients (93 feet) and 30 arthrodesis patients (34 feet) were evaluated. The mean
      age at onset in the current study was 43 years (13-70 years) and only six
      patients developed symptoms at an age of less than 20 years. Hallux rigidus was
      graded based on a five-grade clinical-radiographic system. The mean follow-up was
      8.9 years. Ninety-five percent of patients with a positive family history had
      bilateral disease at the final follow-up. At the initial examination in the
      current study, 81% of patients had radiographic and clinical evidence of
      unilateral disease, but at the final follow-up 79% of patients had radiographic
      and clinical evidence of bilateral disease. Eleven percent of patients in the
      present series had pes planus based on either a positive Harris mat study and/or
      heel valgus. There was no evidence of an Achilles or gastrocnemius tendon
      contracture. Radiographic analysis found that the concurrent presentation of
      hallux valgus and hallux rigidus was not common. Ninety-three of 127 feet (73%)
      had a chevron or flat metatarsophalangeal joint. Thirty-five feet were noted to
      have mild or moderate metatarsus adductus. A long first metatarsal was no more
      common in patients with hallux rigidus than in the general population. The mean
      first ray elevatus was 5.5 mm and was well within acceptable limits of normal.
      The mean first ray mobility was 5 mm in arthrodesis patients and 5.8 mm in
      cheilectomy patients. CONCLUSION: Hallux rigidus was not associated with
      elevatus, first ray hypermobility, a long first metatarsal, Achilles or
      gastrocnemius tendon tightness, abnormal foot posture, symptomatic hallux valgus,
      adolescent onset, shoewear, or occupation. Hallux rigidus was associated with
      hallux valgus interphalangeus, bilateral involvement in those with a familial
      history, unilateral involvement in those with a history of trauma, and female
      gender. Metatarsus adductus was more common in patients with hallux rigidus than
      in the general population but a clear correlation was not found. Additionally, a
      flat or chevron-shaped metatarsophalangeal joint was more common in hallux
      rigidus patients.

PMID- 14587988
TI  - The modified Palmer lateral approach for calcaneal fractures: wound healing and
      postoperative computed tomographic evaluation of fracture reduction.
AB  - In 32 consecutive intra-articular calcaneal fractures (28 patients, 4 bilateral),
      open treatment was done using the modified Palmer lateral approach and the
      reduction was assessed with postoperative radiography and computed tomography
      (CT) (coronal and axial images, 1-2 days after surgery). Retrospective analysis
      of the available radiographs and CT scans was done in 27 fractures (25 patients,
      2 bilateral) to assess accuracy of reduction achieved; in five fractures the
      studies were not available. Sanders classification was type I in 2 (7%), type II
      in 20 (74%), and type III in 5 (19%) fractures; the calcaneocuboid joint was
      involved in 9 (33%) fractures. Reduction included elevation of the depressed
      lateral side of the posterior facet, reduction of the neck (anterior third of
      calcaneus) to the body (middle third of calcaneus), realignment of the posterior
      tuberosity, and reduction of lateral wall blowout; internal fixation was done
      with cannulated screws. Mean (+/-SD) values of the following displacement
      parameters were significantly improved after surgery: Bohler's angle, posterior
      facet angle, lateral posterior facet articular depression, heel width (coronal
      CT), and calcaneal height. There was no significant difference between
      preoperative and postoperative values of mean angle of Gissane, posterior
      tuberosity position, and body width and length on axial CT. One (3%) of the 32
      fractures was associated with preoperative (traumatic) full-thickness skin
      necrosis at the sinus tarsi that required free muscle flap coverage. One (3%)
      postoperative wound healing complication occurred, consisting of wound dehiscence
      and drainage at the central portion of the surgical wound in a smoker, which
      resolved with dressing changes and antibiotics. In conclusion, the modified
      Palmer lateral approach enabled open reduction of major features of calcaneal
      fractures with less soft-tissue risk than more extensile approaches.

PMID- 14587989
TI  - Supramalleolar osteotomy for the treatment of distal tibial angular deformities
      and arthritis of the ankle joint.
AB  - In a 5-year period (1996-2001), the authors performed supramalleolar osteotomies
      for the correction of distal tibial mechanical malalignment of at least 10
      degrees with concomitant pain and with or without radiographic evidence of
      arthritic changes. The method was also applied as an alternative to other common
      procedures for the treatment of a small group of patients with degenerative
      changes of the ankle joint without previous traumatic event and with minimal or
      moderately altered alignment. There were 12 patients (13 feet) with an average
      follow-up of 33.6 months. All osteotomies healed at an average time of 14 weeks.
      The average AOFAS score improved from 53.8 to 87 points, the average ankle score
      in the scale described by Takakura et al. improved from 56.7 to 82, and the
      average pain score improved from 14.6 to 32.3. In the presence of deformity, the
      average tibial-ankle surface angles in both the coronal and the sagittal planes
      were significantly improved. The radiographic degenerative changes in the ankle
      joint showed no evidence of progression. The choice of technique did not
      influence the clinical or radiographic outcome or the healing time of the
      osteotomy.

PMID- 14587990
TI  - Functional outcome after modified Blair tibiotalar arthrodesis for talar
      osteonecrosis.
AB  - BACKGROUND: Osteonecrosis of the talar body is a challenging problem for both
      patient and surgeon. One reconstruction option is an arthrodesis of the tibia to
      the talar neck, as described by Blair, which has the theoretical advantages of
      salvaging some hindfoot height and motion of the subtalar joint. A few case
      series have been published describing outcome after modified Blair fusions, none
      with validated functional outcomes. The purpose of this article is to describe a
      modification of Blair's original technique, and report the functional outcomes in
      a series of patients undergoing this procedure. METHOD: A retrospective review of
      seven patients with talar osteonecrosis undergoing modified Blair tibiotalar
      arthrodesis was performed. The median patient age was 51 (range, 39-78). Median
      follow-up was 20 months (range, 12-112). Two patients required a repeat procedure
      for delayed/nonunion, with subsequent uneventful union. In all patients the
      procedure included compression screw fixation of the talar head to the anterior
      distal tibia, with the two repeat procedures and the most recent patient having
      an additional anterior compression plate and bone graft. Functional outcome
      measures using both the AOFAS ankle-hindfoot score and the SF-36 global health
      outcome measure were obtained at latest follow-up. In addition, radiographic
      assessment of bone union and time to union was determined. RESULTS: Median SF-36
      physical and mental component scores were 46 and 61, respectively. The median
      AOFAS ankle-hindfoot score was 67 out of 100. Median visual analog scales for
      postoperative pain and function were 7.1 and 6.0 respectively, out of a best
      possible score of 10. CONCLUSION: Functional outcome scores after modified Blair
      arthrodesis are lower than similar scores after conventional tibiotalar fusion,
      and much lower than "normal" values; however, the procedure has similar, if not
      lower, complication rates to alternative complex hindfoot reconstructions, and
      this procedure is a valuable alternative in the management of talar osteonecrosis
      with arthrosis.

PMID- 14587992
TI  - Immediate, full weightbearing cast treatment of acute Achilles tendon ruptures: a
      long-term follow-up study.
AB  - Thirty-two patients with 33 ruptures were available for comprehensive evaluation,
      which included a questionnaire, physical examination, and manual as well as
      objective (Kin-Com) strength testing. Data excluding Kin-Com strength testing
      were available in an additional seven patients with seven ruptures; hence, the
      data are based on these 39 patients with 40 ruptures. Five patients with eight
      ruptures were excluded from strength testing but were included in our rerupture
      data, which totaled 44 patients with 48 ruptures. All patients were treated using
      a standard protocol by a single surgeon. All patients were treated within 11 days
      of injury, and the average follow-up was 55 months (range, 24-133). Ninety-five
      percent (38/39) of patients were completely satisfied with their treatment. The
      American Orthopaedic Foot and Ankle Society (AOFAS) ankle hindfoot scores were
      >80 in 97.4% of patients, and the rerupture rate was 6.25% (3/48). Calf
      circumference and ankle range of motion were not statistically different between
      the two legs. The injured leg tended to be slightly weaker than the uninjured
      leg, but the difference was not significant for most of the quantitative strength
      measurements. This study provides data for the Achilles rupture patient who asks,
      "Is there a treatment option other than surgery?" In addition, the standardized
      protocol can be utilized to obtain successful outcomes in those who choose
      nonoperative treatment or are poor surgical candidates.

PMID- 14587991
TI  - Investigation of incidence of superficial peroneal nerve injury following ankle
      fracture.
AB  - The aim of this study was to investigate the incidence of superficial peroneal
      nerve (SPN) injury following ankle fracture and to establish whether this
      differed between those treated by open reduction and internal fixation (ORIF) and
      those treated nonoperatively in a cast. Two hundred eighty patients who had been
      treated for an ankle fracture either surgically (ORIF group) or nonoperatively
      (cast group) were identified. Patients were invited for review, assessed using
      the AOFAS scoring system, and examined for any evidence of SPN injury. The
      surgical approach was documented and all fractures were classified according to
      the Weber classification. A total of 120 patients returned for review; 56
      patients from the ORIF group and 64 patients from the cast group. The mean time
      from injury to review was 2 years (range, 12-36 months). Overall, 18 patients
      (15%) had a symptomatic SPN injury and these patients had a significantly lower
      AOFAS score. In the cast group, 9% of patients had painful symptoms from an SPN
      injury, compared to 21% of patients in the ORIF group (p < .05). No evidence of
      SPN injury was found in those who had a posterolateral approach to the ankle.
      Surgeons should be aware that the SPN is at risk during lateral approach to the
      fibula and that injury to this nerve can frequently be identified as a cause of
      chronic ankle pain.

PMID- 14587993
TI  - Variations on the insertion of the posterior tibialis tendon: a cadaveric study.
AB  - This cadaveric study specifically investigates the variations on the insertion of
      the posterior tibialis tendon (PTT) in the foot, a topic which is not well
      defined in anatomy discussions. The PTT insertion sites from 11 fresh-frozen
      cadaver feet (10 subjects) were evaluated. There were three distinct bands of the
      PTT seen in all specimens with variations on the insertion to the spring ligament
      (4/11), fifth metatarsal base (7/11), flexor hallucis brevis (9/11), and peroneus
      longus (4/11). This study also found a distinct slip to the abductor hallucis in
      five of the specimens.

PMID- 14587994
TI  - The effects of cycling shoe stiffness on forefoot pressure.
AB  - Plantar pressure data were recorded in two different shoe types to determine the
      effect of cycling shoe stiffness on peak plantar forefoot pressure in cyclists.
      Two pairs of shoes of the same size and manufacturer, identical except for
      outsole material and stiffness, were tested. Shoe stiffness measurements were
      collected under controlled conditions and in two different configurations using a
      dynamic hydraulic tensile testing machine. Measurements of plantar pressure were
      done using Pedar capacitive-based sensor insoles while subjects pedaled in a
      seated position at a controlled power output. Power output was set at a constant
      value of 400 W across all subjects by a magnetic resistance trainer unit. The
      pressure distribution in carbon-fiber-composite shoes during cycling was compared
      to cycling shoes made with plastic soles. Carbon fiber shoes presented stiffness
      values 42% and 550% higher than plastic shoes in longitudinal bending and three
      point bending, respectively. The shoes made with carbon fiber produced peak
      plantar pressures 18% higher than those of plastic design (121 kPa vs. 103 kPa, p
      = .005). Competitive or professional cyclists suffering from metatarsalgia or
      ischemia should be especially careful when using carbon fiber cycling shoes
      because the shoes increase peak plantar pressure, which may aggravate these foot
      conditions.

PMID- 14587995
TI  - Eccrine poroma: a differential diagnosis in chronic foot lesions.
AB  - Eccrine poroma is a benign tumor which arises from the intraepidermal portion of
      the eccrine sweat glands. It usually occurs as a solitary lesion in the
      extremity, with the foot and sole as a common site. It may present as a foot
      mass, ulcerative lesion, bleeding lesion, or suspected melanoma. The clinical
      diagnosis is often delayed or inaccurate. Three cases of eccrine poroma on the
      foot are presented. The clinical and histological features, problem in diagnosis,
      chance of recurrence, and potential transformation to eccrine porocarcinoma are
      discussed. It is emphasized that eccrine poroma should be considered in the
      differential diagnosis of chronic foot lesions. Complete excision prevents
      recurrence, excludes dysplastic change, and prevents future malignant change.

PMID- 14587996
TI  - Coalition of bilateral first cuneometatarsal joints: a case report.
AB  - The most common types of tarsal coalition are talocalcaneal and calcaneonavicular
      coalition. This report presents a case of a patient with middle foot pain who was
      diagnosed as having first cuneometatarsal coalition.

PMID- 14587997
TI  - Locked fracture dislocation of the calcaneus treated with minimal open reduction
      and percutaneous fixation: a report of two cases and review of the literature.
AB  - Fractures of the calcaneus with associated locked dislocation of the posterior
      facet have been previously described. Two patients with a calcaneal fracture with
      a locked dislocation of a portion of the posterior facet were treated with
      minimally invasive open reduction and percutaneous screw fixation of the fragment
      with cannulated screws. Both patients had satisfactory reductions and healed the
      fractures without any soft-tissue complications. This technique can be a useful
      addition to the armamentarium of the surgeon treating these injuries, especially
      in the patient at high risk for wound complications.

PMID- 14587998
TI  - Charcot osteoarthropathy in a case of Klippel-Trenaunay-Weber syndrome.
AB  - A case of a patient with Klippel-Trenaunay-Weber syndrome (KTW) with Charcot
      osteoarthropathy is presented. A medline literature review was performed using
      the words Klippel-Trenaunay, orthopaedic, ankle, foot, and Charcot joint. Seven
      articles reported orthopaedic manifestations of KTW. They included limb
      hypertrophy and atrophy, limb-length discrepancies, digital anomalies,
      ulcerations, and spine and hip abnormalities, but no mention of Charcot
      osteoarthropathy. After many years of chronic nonhealing ulcers and repeated
      incision and drainage procedures the patient developed Charcot osteoarthropathy
      of the ankle without evidence of osteomyelitis or peripheral neuropathy but with
      severe deformity that required transtibial amputation.

PMID- 14587999
TI  - Strength of fixation of Ludloff metatarsal osteotomy utilizing three different
      types of Kirschner wires: a biomechanical study.
AB  - Static biomechanical studies have demonstrated that the Ludloff shaft metatarsal
      osteotomy is significantly more stable than other commonly used proximal
      (basilar) osteotomies, such as the proximal crescentic and the proximal chevron.
      High average static bending failure moments have been recorded for the screw
      fixation Ludloff osteotomy construct. The objective of the current study was to
      find a reasonable alternative method of fixation in cases where a short osteotomy
      may not be amenable to adequate screw fixation and in cases where an inadvertent
      intraoperative fracture of the metatarsal occurs and subsequent screw fixation is
      precarious due to inadequate bone stock. A Ludloff osteotomy was performed on 24
      matched pairs of cadaveric specimens to compare the strength of fixation of three
      different types of Kirschner wires (smooth, threaded, and SOC threaded).
      Biomechanical testing with plantar force was carried out, and failure load and
      stiffness were measured for each specimen. The current results indicate that the
      threaded pin construct provides adequate strength for fixation of the Ludloff
      osteotomy in the clinical setting.

PMID- 14588000
TI  - Resonance-enhanced multiphoton ionization and VUV-single photon ionization as
      soft and selective laser ionization methods for on-line time-of-flight mass
      spectrometry: investigation of the pyrolysis of typical organic contaminants in
      the steel recycling process.
AB  - A newly conceived compact and mobile time-of flight mass spectrometer (TOFMS) for
      real-time monitoring of highly complex gas mixtures is presented. The device
      utilizes two selective and sensitive soft ionization techniques, viz., resonance
      enhanced multiphoton ionization (REMPI) and single-photon ionization (SPI) in a
      (quasi)-simultaneous mode. Both methods allow a fragmentationless ionization. The
      REMPI method selectively addresses aromatic species, while with SPI applying
      vacuum ultaviolet light (118 nm) in principle all compounds with an ionization
      potential below 10.5 eV are accessible. This provides comprehensive information
      of the chemical composition of complex matrixes. The combustion and pyrolysis
      behavior of five organic materials typically used in steel processing in China
      was studied. The trace amounts of organic compounds in the gas phase during
      combustion and pyrolysis were monitored selectively and sensitively by real-time
      SPI/REMPI-TOFMS. The measurements were carried out at several constant
      temperatures in the range from 300 to 1190 degrees C in both synthetic air and
      nitrogen. Timely resolved mass spectra reveal the formation and subsequent growth
      of aromatic molecules. At lower temperatures, highly alkylated PAHs predominate,
      while at temperatures above 800 degrees C, the more stable benzene and PAHs
      without side chains prevail. Potential hyphenation of SPI/REMPI-TOFMS to methods
      of thermal analysis is discussed.

PMID- 14588001
TI  - Microfluidic devices for the high-throughput chemical analysis of cells.
AB  - A microfluidic device is reported that integrated cell handling, rapid cell
      lysis, and electrophoretic separation and detection of fluorescent cytosolic
      dyes. The device function was demonstrated using Jurkat cells that were loaded
      with the fluorogenic dyes - carboxyfluorescein diacetate, Oregon green carboxylic
      acid diacetate, or Calcein AM. The loaded cells were hydrodynamically transported
      from the cell-containing reservoir to a region on the microfluidic device where
      they were focused and then rapidly lysed using an electric field. Complete lysis
      was accomplished in <33 ms. The hydrolyzed, fluorescent dyes in the cell lysate
      were automatically injected into a separation channel on the device and detected
      3 mm downstream of the injection point. The total separation time was
      approximately 2.2 s with absolute migration time reproducibilities of <1% and
      efficiencies ranging from 2300 to 4000 theoretical plates. Results from 139 cells
      are reported. A small fraction of these cells, approximately 9%, were found to
      enzymatically hydrolyze the loaded dyes in a manner significantly different from
      the majority of the cells. Cell analysis rates of 7-12 cells/min were
      demonstrated and are >100 times faster than those reported using standard bench
      scale capillary electrophoresis.

PMID- 14588002
TI  - High-throughput miniature cylindrical ion trap array mass spectrometer.
AB  - A fully multiplexed cylindrical ion trap (CIT) array mass spectrometer with four
      parallel ion source/mass analyzer/detector channels has been built to allow
      simultaneous high-throughput analysis of multiple samples. A multielement
      external chemical ionization/electron ionization source was coupled to a parallel
      array of CITs each of equal size (internal radius 2.5 mm), and the signal was
      recorded using an array of four miniature (2-mm inner diameter) electron
      multipliers. Using external electron ionization, the spectra of four separate
      samples were recorded simultaneously in real time using a four-channel
      preamplifier system and a data acquisition program written using LabVIEW
      software. These experiments mark the first demonstration of externally generated
      ions being successfully trapped in a miniature CIT mass analyzer. The instrument
      currently provides mass/charge range of approximately m/z 50-500. Average peak
      width is m/z 0.3, corresponding to a resolution of 1000 at m/z 300. The four
      channel mass spectrometer is housed in a single vacuum manifold and operated with
      a single set of control electronics. The modular design of this instrument allows
      scale-up to many more channels of analysis for future applications in the areas
      of industrial process monitoring and combinatorial analysis and in the fields of
      proteomics and metabolomics.

PMID- 14588004
TI  - Microtubule sensors and sensor array based on polyaniline synthesized in the
      presence of poly(styrene sulfonate).
AB  - Microtubule sensors for glucose, urea, and triglyceride were fabricated based on
      poly(styrene sulfonate)-polyaniline (PSS-PANI) composites synthesized within the
      pores of track-etched polycarbonate membranes. The synthesis of a sufficiently
      thick and conducting PSS-PANI film at pH 5 provided the advantage of immobilizing
      enzymes during polymerization. This resulted in the improvement of sensor
      response for urea and triglyceride by a factor of approximately 10(2) with a
      significant increase in the linear region of response compared to polyaniline
      based sensors, where the enzymes were immobilized by physical adsorption after
      the polymerization. The sensors based on urea and triglyceride were found to have
      a higher linear range of response, better sensitivity, improved multiple use
      capability, and faster response time compared to the potentiometric and
      amperometric sensors based on polyaniline. A microtubule sensor array for
      glucose, urea, and triglyceride based on PSS-PANI was fabricated by
      immobilization of three different sets of enzymes on three closely spaced devices
      and its response was found to be free from cross-interference when a sample
      containing a mixture of the above analytes was analyzed in a single measurement.

PMID- 14588003
TI  - Enzyme-amplified electrochemical detection of DNA using electrocatalysis of
      ferrocenyl-tethered dendrimer.
AB  - We have developed a sandwich-type enzyme-linked DNA sensor as a new
      electrochemical method to detect DNA hybridization. A partially ferrocenyl
      tethered poly(amidoamine) dendrimer (Fc-D) was used as an electrocatalyst to
      enhance the electronic signals of DNA detection as well as a building block to
      immobilize capture probes. Fc-D was immobilized on a carboxylic acid-terminated
      self-assembled monolayer (SAM) by covalent coupling of unreacted amine in Fc-D to
      the acid. Thiolated capture probe was attached to the remaining amine groups of
      Fc-D on the SAM via a bifunctional linker. The target DNA was hybridized with the
      capture probe, and an extension in the DNA of the target was then hybridized with
      a biotinylated detection probe. Avidin-conjugated alkaline phosphatase was bound
      to the detection probe and allowed to generate the electroactive label, p
      aminophenol, from p-aminophenyl phosphate enzymatically. p-Aminophenol diffuses
      into the Fc-D layer and is then electrocatalytically oxidized by the electronic
      mediation of the immobilized Fc-D, which leads to a great enhancement in signal.
      Consequently, the amount of hybridized target can be estimated using the
      intensity of electrocatalytic current. This DNA sensor exhibits a detection limit
      of 20 fmol. Our method was also successfully applied to the sequence-selective
      discrimination between perfectly matched and single-base mismatched target
      oligonucleotides.

PMID- 14588005
TI  - PVC membrane and coated graphite potentiometric sensors based on Et4todit for
      selective determination of samarium(III).
AB  - Solution studies on the binding properties of 4,5,6,7-tetrathiocino[1,2-b:3,4
      b']diimidazolyl-1,3,8,10-tetraethyl-2,9-dithione (Et(4)todit) toward a number of
      cationic species including some lanthanide ions revealed the occurrence of a
      selective 1:1 complexation of the ligand with Sm(3+) ion. Consequently,
      Et(4)todit was used as a suitable neutral ionophore for the preparation of novel
      polymeric membrane (PME) and coated graphite (CGE) Sm(3+)-selective electrodes.
      The electrodes exhibit a Nernstian behavior for Sm(3+) ions over wide
      concentration ranges (1.0 x 10(-5)-1.0 x 10(-1) M for PME and 1.0 x 10(-7)-1.0 x
      10(-1) M for CGE) and very low limits of detection (8.0 x 10(-6) M for PME and
      1.6 x 10(-8) M for CGE). The proposed potentiometric sensors manifest advantages
      of relatively fast response, and, most importantly, good selectivities relative
      to wide variety of other cations, including other lanthanide ions. The
      selectivity behavior of the proposed Sm(3+)-selective electrodes revealed a great
      improvement compared to the best previously reported electrode for samarium(III)
      ion. The potentiometric responses of the electrodes are independent of the pH of
      the test solution in the pH range 4.0-6.5. The electrodes were successfully
      applied to the recovery of Sm(3+) ion from tap water samples and also, as an
      indicator electrode, in potentiometric titration of samarium(III) ions.

PMID- 14588006
TI  - Beta-cyclodextrin-based ferrocene-imprinted gold electrodes.
AB  - A new stepwise self-assembly procedure is described for the preparation of
      functional cyclodextrin-modified electrodes. The approach is based on the
      formation of alkanethiol/lipoylamide-beta-cyclodextrin monolayers with the thiol
      component responsible for blocking of the electrode surface and lipoylamide-beta
      cyclodextrin molecules-for controlled opening of the access of the electroactive
      probe to the electrode. Functionalization of the electrode is achieved by means
      of a new cyclodextrin derivative-mono(6-deoxy-6-lipoylamide)-per-2,3,6-O-acetyl
      beta-cyclodextrin-prepared in the peracetyl form and deacetylated directly on the
      electrode surface following the cyclodextrin self-assembly. The progress of
      deacetylation was monitored by the MALDI MS technique. Deacetylation caused
      opening of the active sites toward solution probes. The response toward ferrocene
      was found to be highly improved when ferrocene was added to the solution
      following self-assembly of cyclodextrin but prior to the thiol self-assembly step
      (imprinting method). The proposed synthesis and sequential monolayer formation
      scheme lead to well-organized and stable modified electrode surfaces with
      improved sensitivity toward solution species compared to other procedures of
      electrode modification with the cyclodextrin derivatives.

PMID- 14588007
TI  - Electrochromatographic retention studies on a flavin-binding RNA aptamer sorbent.
AB  - Aptamers are oligonucleotides that are isolated and amplified on the basis of
      their recognition of a target molecule. In this study, an RNA aptamer isolated
      and amplified on the basis of its affinity for flavin mononucleotide (FMN) was
      covalently bound to the inner walls of fused-silica capillaries. This aptamer
      recognizes the flavin moiety of both FMN and flavin adenine dinucleotide (FAD).
      When an attempt was made to evaluate these capillaries according to existing
      theory, the theory proved to be insufficient. We describe a new method to
      evaluate capillaries for use in open-tubular capillary electrochromatography
      (OTCEC) of charged analytes, which combines OTCEC and flow-counterbalanced
      capillary electrophoresis. This method enabled us to extract k' and evaluate
      k(CEC) values for these capillaries, and the dependence of these values on Mg(2+)
      concentration was explored. The k' values for these capillaries ranged from
      0.0951 to 0.2530 and from 0.0255 to 0.1118 for FMN and FAD, respectively.

PMID- 14588008
TI  - Capillary electrophoresis coupled on-line with ultraviolet resonance Raman
      spectroscopy.
AB  - Capillary electrophoresis (CE) and resonance Raman spectroscopy (RRS) with
      excitation in the deep ultraviolet (UV) region (lambda(ex): 244 or 257 nm) were
      coupled on-line. The potential of this hyphenated technique, denoted as CE-UV
      RRS, for analyte confirmation/identification purposes was explored with aromatic
      sulfonic acids and nucleotides as test compounds. Good-quality UV-RRS spectra
      could be recorded on-the-fly. Identification limits for the nucleotides were in
      the 10-125 microg/mL range. The RRS spectra showed sufficient characteristic
      features to enable analyte confirmation. In addition, the identification power of
      UV-RRS was studied with substituted pyrenes as model compounds. The compounds
      were distinguishable on the basis of their RRS spectra at 244 nm.

PMID- 14588009
TI  - Raman detection of proteomic analytes.
AB  - The compatibility of nonenhanced Raman spectroscopy with chromatographic and mass
      spectroscopic proteomic sensing is demonstrated for the first time. High-quality
      normal Raman spectra are derived from protein solutions with concentrations down
      to 1 microM and 1 fmol of protein nondestructively probed within the excitation
      laser beam. These results are obtained using a drop coating deposition Raman
      (DCDR) method in which the solution of interest is microdeposited (or
      microprinted) on a compatible substrate, followed by solvent evaporation and
      backscattering detection. Representative applications include the DCDR detection
      of insulin derived from an HPLC fraction, nondestructive DCDR followed by MALDI
      TOF of lysozyme, the DCDR detection of protein spots deposited using an ink-jet
      microprinter, and the identification of spectral differences between glycan
      isomers of equal mass (such as those derived from posttranslationally modified
      proteins).

PMID- 14588010
TI  - Toxicological screening with formula-based metabolite identification by liquid
      chromatography/time-of-flight mass spectrometry.
AB  - An analytical procedure was evaluated for the comprehensive toxicological
      screening of drugs, metabolites, and pesticides in 1-mL urine samples by TurboIon
      spray liquid chromatography/time-of-flight mass spectrometry (LC/TOFMS) in the
      positive ionization mode and continuous mass measurement. The substance database
      consisted of exact monoisotopic masses for 637 compounds, of which an LC
      retention time was available for 392. A macroprogram was refined for extracting
      the data into a legible report, utilizing metabolic patterns and preset
      identification criteria. These criteria included +/-30 ppm mass tolerance, a +/
      0.2-min window for absolute retention time, if available, and a minimum area
      count of 500. The limit of detection, determined for 90 compounds, was <0.1 mg/L
      for 73% of the compounds studied and >1.0 mg/L for 6% of the compounds. For
      method comparisons, 50 successive autopsy urine samples were analyzed by this
      method, and the results confirmed by gas chromatography/mass spectrometry
      (GC/MS). Findings for parent drugs were consistent with both methods; in
      addition, LC/TOFMS regularly revealed apparently correct findings for metabolites
      not shown by GC/MS. Mean and median mass accuracy by LC/TOFMS was 7.6 and 5.4
      ppm, respectively. The procedure proved well-suited for tentative identification
      without reference substances. The few false positives emphasized the fact that
      all three parameters, exact mass, retention time, and metabolite pattern, are
      required for unequivocal identification.

PMID- 14588011
TI  - Discrimination of neolacto-series gangliosides with alpha2-3- and alpha2-6-linked
      N-acetylneuraminic acid by nanoelectrospray ionization low-energy collision
      induced dissociation tandem quadrupole TOF MS.
AB  - A combined strategy of thin-layer chromatography immunostaining and negative ion
      nanoelectrospray low-energy CID mass spectrometry was established for the
      differentiation of isomeric alpha2-3 and alpha2-6 sialylated neolacto-series
      monosialogangliosides from human granulocytes. The gangliosides investigated
      differed in the ceramide moiety by substitution with C16:0 or C24:1 fatty acid
      and in their oligosaccharide chains due to nLc4 and nLc6 core structures. With
      respect to the type of sialylation, the homogeneity of the HPLC-purified
      ganglioside fractions was verified by use of specific anti-Neu5Acalpha2-3Galbeta1
      4GlcNAc-R and anti-Neu5Acalpha2-6Galbeta1-4GlcNAc-R antibodies. A clear-cut
      series of fragment ions for both types of isomeric gangliosides, carrying alpha2
      3- and alpha2-6-linked neuraminic acid, respectively, was obtained by low-energy
      CID. Additionally, a characteristic ring cleavage was detected exclusively in all
      species with Neu5Acalpha2-6Galbeta1-4GlcNAc terminus, regardless of ceramide
      fatty acid and oligosaccharide chain lengths. The diagnostic (0,2)X(4/6) ions,
      generated by ring cleavage of an alpha2-6-linked neuraminic acid are accompanied
      by a simultaneous decrease of the corresponding Y(4)/Y(6) ions. These results
      suggest the unequivocal discrimination of individual alpha2-3- and alpha2-6
      sialylated neolacto-series monosialogangliosides by distinct fragmentation
      patterns in low-energy CID tandem MS.

PMID- 14588012
TI  - Surface heterogeneity of six commercial brands of end-capped C18-bonded silica.
      RPLC separations.
AB  - Single component adsorption isotherms of phenol and caffeine were measured on six
      different commercial brands of end-capped C(18)-bonded silica columns (five
      monomeric bonded phases: Kromasil, Waters Symmetry, Phenomenex, Hypersil, and
      Chromolith from Merck; one polymeric bonded phase, Vydac) with the same
      methanol/water solution (30/70, v/v) as the mobile phase. Adsorption data were
      acquired by frontal analysis (FA) for all these columns in the same way.
      Depending on their solubility in the mobile phase, the concentrations used ranged
      between 1 and 100 g/L and between 0.35 and 35 g/L for phenol and caffeine,
      respectively. Twenty-two adsorption data points were recorded over these ranges.
      In each case, the best isotherm model accounting for all sets of adsorption data
      is the bi-Langmuir model, all columns behaving as heterogeneous adsorbents
      despite the endcapping. Depending on the column, the high-energy sites accounts
      for between 30 and 40% and between 4 and 7% of the total saturation capacity for
      phenol and caffeine, respectively. Except for the polymeric phase (Vydac), the
      ratio of the adsorption constants on the high- and low-energy sites is constant
      at around 10 for both phenol and caffeine, corresponding to an average adsorption
      energy difference of 5 kJ/mol between these two sites. The exact nature of the
      high-energy sites is illustrated by the following properties: (i) they have a
      very low selectivity for caffeine, with alpha(caffeine/phenol) close to 0.4 for
      the five monomeric columns, which suggests the complete derivatization of
      residual silanols; (ii) the high-energy sites account for a large fraction of the
      surface area of these packing materials (35% for phenol, 6% for caffeine); (iii)
      there is a small adsorption energy difference between high and low adsorption
      energy sites (5 kJ/mol); and (iv) the adsorption constants increase with
      increasing surface coverage of the monomeric columns. Thus, the high energy sites
      cannot be residual free silanols of the bare silica. More likely, they are
      related to the local heterogeneity of the C(18)-bonded-layer structure. Caffeine
      is more strongly retained on the low-energy sites than phenol (the product q(s,)
      (1)b(1) is larger for caffeine) but the contribution of the high-energy sites
      (q(s,) (2)b(2)) is markedly lower for caffeine than for phenol, despite the
      larger value of the adsorption constant, b(2). Because of a larger molecular
      size, caffeine cannot penetrate as deeply as phenol inside the bonded layer. This
      explains the paradox of a stronger retention for phenol than for caffeine on end
      capped C(18)-bonded stationary phases.

PMID- 14588014
TI  - Electrokinetic transport through rough microchannels.
AB  - Surface roughness is present in most microfluidic devices as a result of the
      microfabrication techniques or particle adhesion. It is highly desirable to
      understand the roughness effect on microscale transport processes. In this study,
      we developed a 3-D, finite-volume-based numerical model to simulate
      electroosmotic transport in microchannels with rectangular prism rough elements
      on the surfaces. Various configurations of roughness were investigated, and the
      results show different degrees of an even-out effect on liquid transport due to
      the roughness-induced local pressure field and the variation of the
      electroosmotic slip boundary velocities. 3D-sample transport through rough
      microchannels was analyzed. The results demonstrate that the sample's transport
      under the electrical field is much faster in the pathway between the rough
      elements; the concentration field in the height and width direction is not
      uniform. The influence of the electrokinetic properties on liquid flow and sample
      transport was studied. It was found that the increase of the electroosmotic
      mobility or the decrease of the electrophoretic mobility can dramatically enhance
      the uniformity of the concentration field.

PMID- 14588013
TI  - Shifts in peptide and protein charge state distributions with varying spray tip
      orifice diameter in nanoelectrospray Fourier transform ion cyclotron resonance
      mass spectrometry.
AB  - The influence of the diameter of the spray tip employed for nano-electrospray
      mass spectrometry (nano-ES-MS) upon mass spectral charge state distributions was
      investigated using angiotensin I (M(r) = 1296), insulin (M(r) = 5774), and
      ubiquitin (M(r) = 8560) as test analytes. Under a variety of experimental
      conditions, the charge state distributions of the test peptides and protein
      consistently shifted toward higher values as the tip orifice diameter decreased.
      This finding indicates that the use of narrow diameter capillaries can promote
      the formation of higher charge state ions that are more reactive precursors in
      tandem mass spectrometry experiments. A detailed comparison of charge state
      distributions obtained for nanospray capillaries of varying diameters was
      undertaken while systematically varying experimental parameters such as sample
      flow rate, analyte concentration, solvent composition, and electrospray current.
      The general tendency to obtain higher charge states from narrow diameter
      capillaries was conserved throughout, but tips with smaller orifices were more
      sensitive to sample flow rate (the average charge state was lowered significantly
      as flow was raised), whereas tips with bigger orifices were more sensitive to
      analyte concentration and pH of the solution (as each was lowered, the average
      charge state increased).

PMID- 14588015
TI  - High-speed free-flow electrophoresis on chip.
AB  - A microfluidic device has been developed for continuous separation in free-flow
      electrophoresis (FFE) mode. A mixture of two fluorescent reagents is separated
      into two component streams in 75 ms using a sample flow rate of 2 nL/s. The
      residence time of sample in the whole separation compartment is 2 s. The
      separation bed volume is 0.2 microL. The chip has also been used for free-flow
      electrophoresis of fluorescein-5-isothiocyanate-labeled amino acids in both
      aqueous and binary media. The short residence time and small sample flow rate
      make the FFE chip feasible for on-line monitoring on production lines and other
      chemical or biochemical processes. The in-house-made chip was composed of a plain
      glass substrate of 1.5-mm thickness and a PDMS layer of 0.3-mm thickness with
      micromachined channels. The channel design presented in this paper is versatile.
      With the same kind of PDMS substrates, chips for various purposes can be made
      depending on the locations of the reservoirs, which are cut out on the PDMS
      substrate. The results presented verify the scaling laws and allow prediction of
      FFE performances comparable to what is now state of the art on capillary
      electrophoresis chips.

PMID- 14588016
TI  - An integrated microfluidic system for reaction, high-sensitivity detection, and
      sorting of fluorescent cells and particles.
AB  - Presented is a novel approach for an integrated micro total analysis system
      (microTAS) based on a microfluidic on-chip device that supports ultrasensitive
      confocal detection of fluorescent cells and particles and subsequently allows for
      their precise sorting in the fluid phase with respect to spectroscopic
      properties, such as brightness and color. The hybrid silicone elastomer/glass
      chip first comprises a branched channel system to initiate fluid mixing and to
      hydrodynamically focus the sample solution down to a thin flow layer, matching
      the size of the confocal detection volume placed at that position and, thus,
      providing a high detection efficiency. In the subsequent on-chip module, the
      dispersed cells or particles can be sorted into two different output channels.
      The sorting process is realized by a perpendicular deflection stream that can be
      switched electrokinetically. The performance of the automated sorting routine is
      demonstrated by precise partition of a mixture of differently colored fluorescent
      beads. Moreover, the specifically branched channel geometry allows for direct
      implementation of reaction steps prior to detection and sorting, which is
      demonstrated by inducing a selective recognition reaction between the fluorescent
      protein R-phycoerythrin and a mixture of live bacterial cells exhibiting or
      lacking the respective surface antigens.

PMID- 14588017
TI  - Fabrication of patterned multicomponent protein gradients and gradient arrays
      using microfluidic depletion.
AB  - We demonstrate that depletion effects in the fluids used to fill a
      poly(dimethylsiloxane) microfluidic device can be used in conjunction with its
      design rules to generate patterned protein gradients. The linear portions of
      these structures can be designed to present gradients of bound protein coverage
      varying from near-saturation to effectively zero-over distances ranging from a
      few hundred micrometers to more than 1 cm by design. Such patterns can be
      developed in a simple, single-channel form as well as in a multichannel gradient
      array of more complex design. The patterning protocols also support the use of
      multiple protein sources, and we demonstrate an assembly process mediated by a
      protein that inhibits adsorption to generate a gradient array in pixel form. We
      describe examples of multiple protein gradient patterns along with simple
      immunoassays to illustrate the scope of the methodology, the activity of the
      patterned proteins, and their recognition in gradient form on a surface. These
      gradients should prove useful to studies in biosensor and bioassay development
      and as substrates for cell culture to study growth and motility.

PMID- 14588018
TI  - Molding of hydrogel microstructures to create multiphenotype cell microarrays.
AB  - The fabrication of mammalian cell-containing poly(ethylene glycol) (PEG) hydrogel
      microstructures on glass and silicon substrates is described. Using photoreaction
      injection molding in poly(dimethylsiloxane) microfluidic channels, three
      dimensional hydrogel microstructures encapsulating cells (fibroblasts,
      hepatocytes, macrophage) were fabricated with cells uniformly distributed to each
      hydrogel microstructure, and the number of cells in each hydrogel microstructure
      was controlled by changing the cell density of the precursor solution. PEG
      hydrogels were modified using an Arg-Gly-Asp (RGD) peptide sequence, with the
      incorporation of RGD into the hydrogel matrix promoting the spreading of
      encapsulated fibroblasts over a 24-h period in culture. Cells remained viable
      encapsulated in these hydrogel microstructures for a period in excess of 1 week
      in culture. Arrays of hydrogel microstructures encapsulating two or more
      phenotypes on a single substrate were successfully fabricated using
      multimicrofluidic channels, creating the potential for multiphenotype cell-based
      biosensors.

PMID- 14588019
TI  - Numerical analysis and experimental estimation of a low-leakage injection
      technique for capillary electrophoresis.
AB  - This paper presents an experimental and numerical investigation into the use of
      low-leakage injection techniques to deliver sample plugs within electrophoresis
      microchips. The study addresses the principal material transport mechanisms such
      as electrokinetic migration, fluid flow, and diffusion and gives detail analyses
      to the double-L injection technique, which employs electrokinetic manipulations
      to avoid sample leakage within the microchip. Electrical potential contour,
      velocity vector, and streamline distribution in the micro CE chip are
      successfully developed. Experimental and numerical testing results show the
      double-L injection technique is capable of reducing sample leakage within cross
      form microfluidic chips. The current study confirms the double-L injection
      technique has an exciting potential for use in high-quality, high-throughput
      chemical analysis applications and in many other applications throughout the
      field of micro total analysis systems.

PMID- 14588020
TI  - Critical flocculation concentrations, binding isotherms, and ligand exchange
      properties of peptide-modified gold nanoparticles studied by UV-visible,
      fluorescence, and time-correlated single photon counting spectroscopies.
AB  - Protocols for modifying gold nanoparticles with peptide-bovine serum albumin
      (BSA) conjugates are described within. The resulting constructs were
      characterized using a number of techniques including static fluorescence
      spectroscopy and time-correlated single photon counting spectroscopy (TCSPC) in
      order to quantify peptide-BSA binding isotherms, exchange rates, critical
      flocculation concentrations, and the composition of mixed peptide-BSA monolayers
      on gold nanoparticles. TCSPC has proven to be a powerful technique for observing
      the microenvironment of protein-gold nanoparticle conjugates because it can
      distinguish between surface-bound and solution-phase species without the need for
      separation steps. Full characterization of the composition and stability of
      peptide-modified metal nanoparticles is an important step in their use as
      intracellular delivery vectors and imaging agents.

PMID- 14588021
TI  - Identification of chemically selective displacers using parallel batch screening
      experiments and quantitative structure efficacy relationship models.
AB  - Parallel batch screening experiments were carried out to examine how displacer
      chemistry and salt counterions affect the selectivity of batch protein
      displacements in anion exchange chromatographic systems. The results indicate
      that both salt type and displacer chemistry can have a significant impact on the
      amount of protein displaced. Importantly, the results indicate that, by changing
      the displacer, salt counterion, or both, one can induce significant selectivity
      changes in the relative displacement of two model proteins. This indicates that
      highly selective separations can be developed in ion exchange systems by the
      appropriate selection of displacer chemistry and salt counterion. The
      experimental batch screening data were also used in conjunction with various
      molecular descriptors to generate quantitative structure efficacy relationship
      (QSER) models based on a support vector machine feature selection and regression
      tool. The models resulted in good correlations and successful predictions for an
      external test set of displacers. A star plot approach was shown to be a powerful
      tool to aid in the interpretation of the QSER models. These results indicate that
      this modeling approach can be employed for the a priori prediction of displacer
      efficacy as well as for providing insight into displacer design and the selection
      of proper mobile-phase conditions for highly selective separations.

PMID- 14588022
TI  - T3-sequencing: targeted characterization of the N- and C-termini of undigested
      proteins by mass spectrometry.
AB  - A novel extension of the "top-down" approach is introduced for the selective
      characterization of protein termini that does not involve proteolytic digestion
      steps. N- and C-terminal peptides were generated from intact proteins in the mass
      spectrometer and further analyzed by MS/MS-an approach referred to as T(3)
      sequencing. N-terminal and C-terminal fragment ion series were obtained by the
      pseudo-MS/MS technique in-source decay (ISD) on a matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometer (MALDI-TOF MS). These ions
      provided near-terminal sequence tags from the undigested protein in the ISD
      spectrum acquired in reflector mode and allowed to screen for the proper
      processing state of the terminus with respect to a reference sequence. In the
      second step of T(3)-sequencing, the precursor ions, which have been generated by
      ISD and which included the N- or C-terminal sequence, were selected in the timed
      ion gate of a MALDI-TOF/TOF mass spectrometer for MS/MS analysis. These spectra
      allowed identification of the protein, the proper definition of both termini, and
      allowed confirmation of suspected terminal modifications. T(3)-Sequencing appears
      to be an alternative to classical Edman sequencing, which is fast and even
      permits the analysis of N-terminally blocked proteins and their C-terminus.

PMID- 14588023
TI  - Electrogenerated chemiluminescence. 72. Determination of immobilized DNA and C
      reactive protein on Au(111) electrodes using tris(2,2'-bipyridyl)ruthenium(II)
      labels.
AB  - Anodic electrogenerated chemiluminescence (ECL) with tri-n-propylamine (TPrA) as
      a coreactant was used to determine DNA and C-reactive protein (CRP) by
      immobilizations on Au(111) electrodes using tris(2,2'-bipyridyl)ruthenium(II)
      (Ru(bpy)(3)(2+)) labels. A 23-mer synthetic single-stranded (ss) DNA derived from
      the Bacillus anthracis with an amino-modified group at the 5' end position was
      covalently attached to the Au(111) substrate precoated with a self-assembled
      thiol monolayer of 3-mercaptopropanoic acid (3-MPA) in the presence of 1-ethyl-3
      (3-dimethylaminopropyl) carbodiimide hydrochloride (EDAC) and then hybridized
      with a target ssDNA tagged with Ru(bpy)(3)(2+) ECL labels. Similarly,
      biotinylated anti-CRP species were immobilized effectively onto the Au(111)
      substrate precovered with a layer of avidin linked covalently via the reaction
      between avidin and a mixed thiol monolayer of 3-MPA and 16-mercaptohexadecanoic
      acid on Au(111) in the presence of EDAC and N-hydroxysuccinimide. CRP and anti
      CRP tagged with Ru(bpy)(3)(2+) labels were then conjugated to the surface layer.
      ECL responses were generated from the modified electrodes described above by
      immersing them in a TPrA-containing electrolyte solution. A series of electrode
      treatments, including blocking free -COOH groups with ethanol amine, pinhole
      blocking with bovine serum albumin, washing with EDTA/NaCl/Tris buffer, and
      spraying with inert gases, were used to reduce the nonspecific adsorption of the
      labeled species. The ECL peak intensity was linearly proportional to the analyte
      CRP concentration over the range 1-24 microg/mL. CRP concentrations of two
      unknown human plasma/serum specimens were measured by the standard addition
      method based on this technique.

PMID- 14588024
TI  - Neurosteroids in rat brain: extraction, isolation, and analysis by nanoscale
      liquid chromatography-electrospray mass spectrometry.
AB  - A method designed for the analysis of sulfated neurosteroids and unconjugated
      ketonic neurosteroids in rat brain using nanoscale liquid chromatography
      electrospray (nano-LC-ES) mass spectrometry is described. Neurosteroids in rat
      brain tissue were extracted, purified, and separated into two groups, neutral
      unconjugated steroids and steroid sulfates, by employing solid-phase partition,
      cation- and anion-exchange chromatography. The steroid sulfate fraction was
      analyzed by nano-LC-ES mass spectrometry. Contrary to expectations, the sulfates
      of pregnenolone and dehydroepiandrosterone (DHEA) were not detected. Internal
      standards, including pregnenolone sulfate, were recovered and the detection limit
      of the method was 0.3 ng/g of wet brain. Cholesterol sulfate was detected at a
      level of 1.2 microg/g of wet brain. The neutral unconjugated steroid fraction was
      derivatized with hydroxylamine hydrochloride to convert oxosteroids into their
      oximes. The oximes were isolated using cation-exchange chromatography and were
      analyzed by nano-LC-ES tandem mass spectrometry. The analyses of the neutral
      unconjugated steroid fraction confirmed the presence in rat brain of
      pregnenolone, pregnanolone isomers, progesterone, testosterone, and DHEA, which
      were characterized by their retention times, the mass of the protonated
      molecules, and characteristic fragment ions. The levels were estimated by
      addition of [3,4-(13)C(2)]-progesterone as an internal standard and found to be
      in a range of 0.04-20 ng/g.

PMID- 14588025
TI  - Separation of cisplatin and its hydrolysis products using electrospray ionization
      high-field asymmetric waveform ion mobility spectrometry coupled with ion trap
      mass spectrometry.
AB  - Cisplatin and its mono- and dihydrated complexes have been separated using a high
      field asymmetric waveform ion mobility spectrometry (FAIMS) analyzer interfaced
      with electrospray ionization (ESI) and ion trap mass spectrometry (ITMS). The
      addition of helium to the nitrogen curtain/carrier gas in the FAIMS device
      improved both the sensitivity and selectivity of the electrospray analysis.
      Introduction of a three-component mixture as curtain/carrier gas, nitrogen,
      helium, and carbon dioxide, resulted in further improvements to sensitivity.
      Compared with conventional ESI-MS, the background chemical noise in the ESI-FAIMS
      ITMS spectrum was dramatically reduced, resulting in over 30-fold improvement in
      the signal-to-noise ratio for cisplatin. Analytical results were linear over the
      concentration range 10-200 ng/mL for intact cisplatin with a corresponding
      detection limit determined of 0.7 ng/mL with no derivatization or chromatographic
      separation prior to analysis.

PMID- 14588026
TI  - Quantitation of endogenous analytes in biofluid without a true blank matrix.
AB  - A method is presented that describes a reliable and practical procedure for
      quantitation of an analyte present at relatively high background levels in blank
      (untreated) biological matrixes. Using a "surrogate analyte" approach, an
      endogenous analyte was quantitated in a variety of biological matrixes containing
      both very low (<10 ng/mL) and high (>2000 ng/mL) background levels of the desired
      analyte. This quantitative "surrogate analyte" approach was applied during the
      development of an HPLC/MS method for alpha-ketoisocaproic acid (KIC), which was
      identified as a potential biomarker for branched chain amino acid transferase
      inhibitor activity. Using deuterium-labeled KIC (d(3)) as a surrogate analyte,
      not an internal standard, to generate the calibration curve, the concentration of
      KIC in biofluid could be back-calculated based on the regression equation and
      response factor of KIC to KIC-d(3). In particular, this approach made it possible
      to prepare standards in control biofluid such as plasma, which greatly
      facilitated the process of method development. For the validated method, a linear
      range of 10-5000 ng/mL for KIC-d(3) was observed. Intraday and interday
      experimental accuracy, calculated as percent error, were in the range of < or
      =10% for KIC-d(3). This method is simple, rapid, and reliable for the
      quantitation of KIC in plasma, brain homogenate, cerebrospinal fluid, and other
      biological samples from discovery and pharmacological studies.

PMID- 14588027
TI  - Supercritical fluid generated stationary phases for liquid chromatography and
      capillary electrochromatography.
AB  - Chromatographic silica-bonded stationary phases have been prepared using
      supercritical CO(2) as the reaction medium. (29)Si solid-state NMR spectra of the
      generated bonded silica phases show unreacted silica species Q(3) and Q(4),
      alongside important resonances for surface-bound ligands, T(1), T(2), and T(3).
      Initially, a fluorinated octyl silica (C(8)) phase was produced, by reacting
      (1)H,(1)H,(2)H,(2)H-perfluorooctyltriethoxysilane with silica particles (3
      microm) in sc-CO(2) at 60 degrees C and 450 atm for 3 h. In-house-packed LC
      columns of this fluorinated sc-C(8) silica phase yielded typical reversed-phase
      behavior when a standard test mix of benzamide (k' = 1.03), benzophenone (k' =
      8.11), and biphenyl (k' = 14.92) was eluted. When packed into fused-silica
      capillaries for CEC, this fluorinated sc-C(8) silica phase gave linear plots of
      log k' versus percentage MeOH for benzophenone and biphenyl and, in contrast to
      octyl or octadecyl silica phases, displayed selectivity for aromatic thioureas
      when chromatographed among a series of synthetic organic thiourea test solutes.
      Similarily, an octadecyl silica phase (sc-C(18) silica) was prepared by reaction
      of n-octadecyltriethoxysilane in sc-CO(2), packed at 9500 psi and examined by LC.
      The sc-C(18) silica LC column yielded high column efficiency (up to 141 000 N/m
      (fluorene)) and excellent asymmetry factors (1.06, fluorene) without resource to
      end-capping. Following a second silylating or end-capping step using
      hexamethyldisilazane in sc-CO(2), sc-end-capped sc-C(18) silica phases elute N,N
      DMA before toluene and the toluidine isomers as a single peak, indicating lowered
      silanol activity according to the Engelhardt test. A rapid separation of the
      important pharmaceutical substances, ketoprofen, naproxen, fentoprofen, and
      ibuprofen, on an sc-end-capped sc-C(18) silica phase is also shown.

PMID- 14588028
TI  - Use of ionic liquids for liquid-phase microextraction of polycyclic aromatic
      hydrocarbons.
AB  - This paper demonstrates, for the first time, that ionic liquids (IL) such as 1
      octyl-3-methylimidazolium hexafluorophosphate ([C(8)MIM][PF(6)]) are excellent
      extraction solvents in liquid-phase microextraction (LPME). The unique properties
      of nonvolatility and adequate viscosity allow IL to be conveniently adopted as
      extraction solvents in both direct-immersion and headspace LPME. Model compounds,
      polycyclic aromatic hydrocarbons (PAHs), are conveniently and rapidly enriched in
      a 3-microL drop of [C(8)MIM][PF(6)] suspended on the tip of a microsyringe
      followed by liquid chromatographic determination. Compared to 1-octanol, a larger
      volume drop of [C(8)MIM][PF(6)] can be formed and survive for a longer extraction
      time; therefore, a much higher enrichment factor for PAHs can be reached. For low
      volatility PAHs, direct-immersion LPME provides higher enrichment factors than
      that of headspace LPME. However, the enrichment factor obtained by headspace LPME
      was almost 3-fold of that by direct-immersion LPME in a 30-min extraction of the
      most volatile PAH, naphthalene. For 30-min direction-immersion LPME of EPA
      priority PAHs, the enrichment factor, correlation coefficient (R(2)), and
      reproducibility (RSD, n = 5) were in the range of 42-166, 0.9169-0.9976, and 2.8
      12%, respectively. Considering that IL can be easily prepared from relatively
      inexpensive materials and tuned by combination of different anions and cations
      for task-specific extraction of analytes from various solvent media, this
      proposed method should have great potentiality in sample preparation.
      Furthermore, the nonvolatility of IL makes it potentially useful for headspace
      LPME of volatile analytes.

PMID- 14588029
TI  - Characterization of a thermally induced irreversible conformational transition of
      amylose tris(3,5-dimethylphenylcarbamate) chiral stationary phase in
      enantioseparation of dihydropyrimidinone acid by quasi-equilibrated liquid
      chromatography and solid-state NMR.
AB  - A thermally induced irreversible conformational transition of amylose tris(3,5
      dimethylphenylcarbamate) (i.e., Chiralpak AD) chiral stationary phase (CSP) in
      the enantioseparation of dihydropyrimidinone (DHP) acid racemate was studied for
      the first time by quasi-equilibrated liquid chromatography with cyclic van't Hoff
      and step temperature programs and solid-state ((13)C CPMAS and (19)F MAS) NMR
      using ethanol and trifluoroacetic acid (TFA)-modified n-hexane as the mobile
      phase. The conformational transition was controlled by a single kinetically
      driven process, as evidenced by the chromatographic studies. Solid-state NMR was
      used to study the effect of the temperature on the conformational change of the
      solvated phase (with or without the DHP acid enantiomers and TFA) and provided
      some viable structural information about the CSP and the enantiomers.

PMID- 14588030
TI  - Elution-extrusion countercurrent chromatography. Use of the liquid nature of the
      stationary phase to extend the hydrophobicity window.
AB  - Countercurrent chromatography (CCC) is a liquid chromatography technique with a
      liquid stationary phase. Taking advantage of the liquid nature of the stationary
      phase, it is possible to perform unique operations not possible in classical
      liquid chromatography with a solid stationary phase. It is easy to avoid any
      solute-irreversible absorption in the CCC column. If the retention volumes of
      solutes become too high, the dual mode will be used. The roles of the phases are
      reversed. The stationary phase becomes the mobile phase, and the CCC column is
      started again. The solutes elute rapidly in what was previously the stationary
      phase. The theoretical basis of the dual-mode method is recalled. The dual-mode
      method is a discontinuous method. The separation should be stopped when the phase
      switch is performed. The elution-extrusion procedure is another way to avoid any
      irreversible adsorption of solutes in the column. The method uses the fact that
      the liquid volumes occupied by the solutes highly retained inside the column can
      be orders of magnitude lower than the mobile-phase volume that would be needed to
      elute them. The elution-extrusion method also has two steps: the first step is a
      regular CCC chromatogram. Next, the stationary phase containing the partially
      separated hydrophobic solutes is extruded out of the column in a continuous way
      using the liquid stationary phase. The theory of the process is developed and
      compared to the dual-mode theory. Alkylbenzene homologues are experimentally used
      as model compounds with the heptane/methanol/water biphasic liquid system to
      establish the theoretical treatment and compare the performance of two types,
      hydrodynamic and hydrostatic, of CCC columns. It is shown that the method can
      dramatically boost the separation power of the CCC technique. An apparent
      efficiency higher than 20 000 plates was obtained for extruded octylbenzene and a
      160-mL hydrodynamic CCC column with less than 500 plates when conventionally
      used.

PMID- 14588031
TI  - Effect of polyelectrolyte multilayers on the response of a quartz crystal
      microbalance.
AB  - The effect of a polyelectrolyte (PE) multilayers made by a layer-by-layer
      technique on the response of a quartz crystal microbalance (QCM) is studied by
      using novel mathematical methods based on the Mobius transformations and their
      matrix representations in the complex plane. In the first method, the basic
      properties of the Mobius transformation are used for obtaining the PE bilayer
      matrix from the QCM impedance measurements taken at four different numbers of
      layers. In the second method, nonlinear fitting with concomitant error estimation
      is used for obtaining the elements of the bilayer matrix. The methods are applied
      to a multilayer composed of 150 bilayers of poly(sodium 4-styrenesulfonate) and
      poly(diallyldimethylammonium) chloride on a quartz crystal resonator. The
      structure of the system is discussed, and the bulk acoustic impedance and areal
      mass density of the bilayer are calculated from the layer matrix.

PMID- 14588032
TI  - Multivariate calibration standardization across instruments for the determination
      of glucose by Fourier transform near-infrared spectrometry.
AB  - The transfer of multivariate calibration models is investigated between a primary
      (A) and two secondary Fourier transform near-infrared (near-IR) spectrometers (B,
      C). The application studied in this work is the use of bands in the near-IR
      combination region of 5000-4000 cm(-)(1) to determine physiological levels of
      glucose in a buffered aqueous matrix containing varying levels of alanine,
      ascorbate, lactate, triacetin, and urea. The three spectrometers are used to
      measure 80 samples produced through a randomized experimental design that
      minimizes correlations between the component concentrations and between the
      concentrations of glucose and water. Direct standardization (DS), piecewise
      direct standardization (PDS), and guided model reoptimization (GMR) are evaluated
      for use in transferring partial least-squares calibration models developed with
      the spectra of 64 samples from the primary instrument to the prediction of
      glucose concentrations in 16 prediction samples measured with each secondary
      spectrometer. The three algorithms are evaluated as a function of the number of
      standardization samples used in transferring the calibration models. Performance
      criteria for judging the success of the calibration transfer are established as
      the standard error of prediction (SEP) for internal calibration models built with
      the spectra of the 64 calibration samples collected with each secondary
      spectrometer. These SEP values are 1.51 and 1.14 mM for spectrometers B and C,
      respectively. When calibration standardization is applied, the GMR algorithm is
      observed to outperform DS and PDS. With spectrometer C, the calibration transfer
      is highly successful, producing an SEP value of 1.07 mM. However, an SEP of 2.96
      mM indicates unsuccessful calibration standardization with spectrometer B. This
      failure is attributed to differences in the variance structure of the spectra
      collected with spectrometers A and B. Diagnostic procedures are presented for use
      with the GMR algorithm that forecasts the successful calibration transfer with
      spectrometer C and the unsatisfactory results with spectrometer B.

PMID- 14588033
TI  - Chemiluminometric measurement of atmospheric ozone with photoactivated
      chromotropic acid.
AB  - A highly sensitive, robust, fast, affordable measurement system based on
      interfacial gas-liquid chemiluminescence (CL) on a wetted transparent screen
      directly on top of a miniature photomultiplier tube provides the basis of an
      attractive method for ozone (O(3)). Alkaline chromotropic acid (CA, 4,5
      dihydroxynaphthalene-2,7-disulfonic acid) chemiluminesces upon exposure to ozone.
      No light emission is observed from exposure of alkaline CA to NO(2) or H(2)O(2).
      However, response to ozone is highly dependent on the age and storage condition
      of the CA solution. As such, quantitative analysis will require frequent
      calibration, and the method will not be attractive. We have discovered that
      photoactivation plays the key role in producing (a) compound(s) from chromotropic
      acid that appear(s) to be the primary agent(s) responsible for the CL reaction
      with O(3). We thus devised a method wherein a flowing solution of CA (that is
      stable in neutral/acidic solutions) is rendered alkaline and then exposed for a
      few seconds on-line to UV radiation. The solution then reacts with ozone on a
      screen consisting of an "invisible" nylon stocking that provides for low liquid
      residence time and high light throughput and results in an LOD of 40 pptv, a
      determination range at least up to 230 ppbv, and 10-90% and 90-10% response times
      of 130 and 80 ms, respectively. Intra- and interday repeatabilities at the same
      concentration were 0.32 and 3.8% in relative standard deviation. On the basis of
      aging, CL, chromatography, and chromatography-mass spectrometry studies, we
      suggest that the primary CL-active species are likely dimeric semiquinone species
      derived from CA by a series of radical reactions.

PMID- 14588034
TI  - Fluorescent molecular thermometers based on polymers showing temperature-induced
      phase transitions and labeled with polarity-responsive benzofurazans.
AB  - Poly(N-isopropylacrylamide) in aqueous solution undergoes a phase transition at
      approximately 32 degrees C. The fluorescence properties of benzofurazans are
      affected by solvent polarity. We combine these two characteristics for the first
      time to develop sensitive fluorescent molecular thermometers. Five fluorescent
      monomers having a benzofurazan skeleton were synthesized, and the copolymers of N
      isopropylacrylamide (NIPAM) and a small quantity of the fluorescent monomer were
      obtained to investigate their fluorescence properties. With increase in
      temperature, the copolymers in water showed the temperature-induced phase
      transition at approximately 32 degrees C and the fluorescence intensities of the
      copolymers concurrently increased. Especially, for the copolymer of 4-N-(2
      acryloyloxyethyl)-N-methylamino-7-N,N-dimethylaminosulfonyl-2,1,3-benzoxadiazole
      and NIPAM, the fluorescence intensity at 37 degrees C was 13.3-fold that seen at
      29 degrees C. The sensitive range of temperature of these fluorescent molecular
      thermometers is changed by the replacement of the NIPAM units by N
      isopropylmethacrylamide or N-n-propylacrylamide units in the copolymers. The
      basis of these fluorescent molecular thermometers is the decrease in the
      microenvironmental polarities near the main chains of the copolymers with
      increasing temperature, as confirmed from the maximum emission wavelengths of the
      benzofurazan units in the copolymers. The responses from the copolymers to the
      change in temperature are reversible and exactly repeatable during at least 10
      cycles of heating and cooling.

PMID- 14588035
TI  - Femtomolar detection of prostate-specific antigen: an immunoassay based on
      surface-enhanced Raman scattering and immunogold labels.
AB  - A novel reagent for low-level detection in immunoadsorbent assays is described.
      The reagent consists of gold nanoparticles modified to integrate bioselective
      species (e.g., antibodies) with molecular labels for the generation of intense,
      biolyte-selective surface-enhanced Raman scattering (SERS) responses in
      immunoassays and other bioanalytical applications. The reagent is constructed by
      coating gold nanoparticles (30 nm) with a monolayer of an intrinsically strong
      Raman scatterer. These monolayer-level labels are bifunctional by design and
      contain disulfides for chemisorption to the nanoparticle surface and succinimides
      for coupling to the bioselective species. There are two important elements in
      this label design; it both minimizes the separation between label and particle
      surface and maximizes the number of labels on each particle. This approach to
      labeling also exploits several other advantages of SERS-based labels: narrow
      spectral bandwidth, resistance to photobleaching and quenching, and long
      wavelength excitation of multiple labels with a single excitation source. The
      strengths of this strategy are demonstrated in the detection of free prostate
      specific antigen (PSA) using a sandwich assay format based on monoclonal
      antibodies. Detection limits of approximately 1 pg/mL in human serum and
      approximately 4 pg/mL in bovine serum albumin have been achieved with a
      spectrometer readout time of 60 s. The extension of the method to multianalyte
      assays (e.g., the simultaneous determination of the many complexed forms of PSA)
      is discussed.

PMID- 14588036
TI  - Mass spectrometric analysis of DNA mixtures: instrumental effects responsible for
      decreased sensitivity with increasing mass.
AB  - Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry has
      demonstrated great potential to replace gel electrophoresis for DNA sequence
      analysis. A current limitation in this method is, however, the decreased
      sensitivity with increasing mass of DNA molecules. In the present study,
      instrumental effects on the mass analysis of DNA molecules were investigated
      quantitatively using an equimolar DNA mixture. It is shown that detection
      efficiency, detector saturation, and ion beam divergence account for the entirety
      of the observed falloff in signal intensity with increasing mass. Although the
      present study focused upon the analysis of DNA mixtures, the instrumental effects
      observed apply equally to other macromolecular mixtures (e.g., proteins,
      polymers).

PMID- 14588037
TI  - Urinary benzo[a]pyrene and its metabolites as molecular biomarkers of asphalt
      fume exposure characterized by microflow LC coupled to hybrid quadrupole time-of
      flight mass spectrometry.
AB  - As a step to study the health effects of asphalt fume exposure, an analytical
      method was developed to characterize benzo[a]pyrene and its hydroxy metabolites
      in the urine of asphalt fume-exposed rats. This method is based on microflow
      liquid chromatography (LC) coupled to hybrid quadrupole orthogonal acceleration
      time-of-flight mass spectrometry (Q-TOFMS). Twenty-four female Sprague-Dawley
      rats were used in the experiment, with 8 as controls and 16 exposed to asphalt
      fumes in a whole-body inhalation chamber for 10 days (4 h/day). Generated at 150
      degrees C, the asphalt fume concentration in the animal exposure chamber ranged
      76-117 mg/m(3). In the urine of the asphalt fume-exposed rats, benzo[a]pyrene and
      its metabolites of 3-hydroxybenzo[a]pyrene, benzo[a]pyrene-7,8-dihydrodiol(+/-),
      and benzo[a]pyrene-7,8,9,10-tetrahydrotetrol(+/-) were identified, and their
      concentrations were determined at 2.19 +/- 0.49, 16.17 +/- 0.3, 6.28 +/- 0.36,
      and 29.35 +/- 0.26 ng/100 mL, respectively. The metabolite concentrations from
      the controlled group, however, were either under the detection limits or at a
      relatively very low level (0.19 +/- 0.41 ng/100 mL for benzo[a]pyrene-7,8,9,10
      tetrahydrotetrol metabolite). The results clearly indicate that the
      benzo[a]pyrene and its hydroxy metabolites were significantly elevated (p <
      0.001) in the urine of asphalt fume-exposed rats relative to controls. The study
      also demonstrated that the combination of microflow LC separation and collision
      induced dissociation leading to a characteristic fragmentation pattern by hybrid
      Q-TOFMS offers a distinct advantage for the identifications and characterizations
      of the benzo[a]pyrene metabolites.

PMID- 14588038
TI  - Characterization of hydrophobic peptides by atmospheric pressure photoionization
      mass spectrometry and tandem mass spectrometry.
AB  - The use of photoionization at atmospheric pressure shows great potential for the
      mass analysis of large apolar or hydrophobic peptides. Mass spectra that were
      obtained using this technique showed mainly singly charged ions. While polar
      peptides spectra do not produce fragment ions, others lead to B-type or C-type in
      source fragmentation. These dissociation reactions, which could involve electron
      capture dissociation processes in the case of the C-type ions, are observed for
      hydrophobic peptides. Both the compatibility of this ionization mode with
      reversed- or normal-phase liquid chromatographic separation and its sensitivity
      allow liquid chromatography coupling to both mass spectrometry and tandem mass
      spectrometry for the analyses of hydrophobic peptide mixtures. Atmospheric
      pressure photoionization seems to be an interesting alternative method to study
      hydrophobic peptides that are not easily ionizable by more classical ionization
      techniques such as electrospray ionization and matrix-assisted laser
      desorption/ionization.

PMID- 14588039
TI  - Development of LC/MS/MS methods for cocktail dosed Caco-2 samples using
      atmospheric pressure photoionization and electrospray ionization.
AB  - Good reliability of Caco-2 permeability studies requires competent sampling and
      analytical methods to ensure the comparability of day-to-day experiments. In this
      work, two n-in-one LC/MS/MS methods based on two different ionization techniques
      were developed and validated for a group of reference compounds; eight of them
      are recommended by the Food and Drug Administration (FDA) for the evaluation of
      oral drug permeability. The performance of a new ionization technique,
      atmospheric pressure photoionization (APPI), as an interface for quantitative
      LC/MS analysis was evaluated in comparison to the electrospray ionization (ESI).
      Generally, the validation parameters, including sensitivity, accuracy, and
      repeatability, were comparable for the APPI and ESI methods. The main difference
      was that the linear quantitative range of APPI was 3-4 orders of magnitude (r(2)
      >/= 0.998) whereas in ESI it was typically 2-3 orders of magnitude (r(2) >/=
      0.990). By the APPI and ESI methods, the simultaneous analysis of nine highly
      heterogeneous compounds was achieved within 5.5-7 min, which leads to significant
      savings in time and cost of the analyses. The successful validation data indicate
      the usefulness of both the methods for the rapid and sensitive (LOD values
      typically </=5 nM) testing of drug transport across the Caco-2 monolayers, and
      after case-specific modification, the methods enable the permeability screening
      of new drug candidates. The applicability and reliability of both methods was
      demonstrated with a real batch of Caco-2 samples, each providing similar values
      of apparent permeability (P(app)). In addition, the individual permeabilities of
      the compounds in the cocktail experiments correlated closely to the ones obtained
      from single-compound experiments.

PMID- 14588040
TI  - Incorporation of a venturi device in electrospray ionization.
AB  - Electrospray ionization has grown to be one of the most commonly used ionization
      techniques for mass spectrometry, and efforts continue to improve its
      performance. Typically, the sprayer tip must be very close to the entrance
      orifice of the mass spectrometer in order to maximize the conduction of ions from
      the sprayer into the mass spectrometer. However, because of space-charge
      repulsion, most ions never reach the sampling orifice. In this work, an
      industrial air amplifier, for which the working mechanism is based on venturi and
      coanda effects, was added between an electrospray ionization source and a time-of
      flight mass spectrometer. When a series of reserpine solutions (0.5, 1.0, 5.0,
      and 10.0 microM) were monitored using mass spectrometry, an over 5-fold increase
      in m/z 609.3 ion intensity was measured for a separation distance of 14 mm
      between the electrospray tip and interface capillary inlet, as compared to when
      the electrospray tip was in its normal position 1 mm in front of the inlet
      without the amplifier. When a voltage was applied to the air amplifier to further
      assist in focusing the electrosprayed ions, an approximately 18-fold increase in
      m/z 609.3 ion intensity was obtained. In addition, a 34-fold reduction in method
      detection limit was observed.

PMID- 14588042
TI  - Applications of electron-ion dissociation reactions for analysis of polycationic
      chitooligosaccharides in Fourier transform mass spectrometry.
AB  - Singly protonated, doubly protonated, and sodiated pentaglucosamide (GlcNAc)(5),
      oligoglucosamines (GlcN)(m)(), and (GlcN)(3)GlcN(3OH14:0) were analyzed in an
      FTICR mass spectrometer by electron-ion dissociation reactions and compared to
      collision activation. The general fragmentation mode was found as the
      asymmetrical sequence fragments (B(n)() and minor C(n)() ion series) with full
      sequence coverage. Molecular mass information of each glucosamide or glucosamine
      residue can be readily obtained from the ion series. Fragmentation by electron
      capture dissociation revealed additional fragmentation of the N-acetyl moiety
      compared to sustained off-resonance irradiation collision-activated dissociation
      (SORI-CAD) and electron-induced dissociation (EID). Sodiated GlcNAc(5) molecular
      adduct ions were analyzed by EID and compared to CAD. Both techniques provided
      full sequence coverage. EID was more effective, but CAD resulted in the cross
      ring ion products (0,2)A(n)() and (2,4)A(n)() for all relevant glucosamide
      residues.

PMID- 14588041
TI  - On-column sample enrichment for capillary electrophoresis sheathless electrospray
      ionization mass spectrometry: evaluation for peptide analysis and protein
      identification.
AB  - Although several designs have been advanced for coupling sample enrichment
      devices to a sheathless electrospray ionization-mass spectrometry (MS) interface
      on a capillary electrophoresis (CE) column, most of these approaches suffer from
      difficulties in fabrication, and the CE separation efficiency is degraded as a
      result of the presence of coupling sleeves. We have developed a design that
      offers significant improvements in terms of ease of fabrication, durability, and
      maintenance of the integrity of the CE-separated analyte zones. Capillaries with
      different inside and outside diameters were evaluated to optimize the performance
      of the CE-MS system, resulting in a mass limit of detection of 500 amol for
      tandem MS analysis of a standard peptide using a 20-microm-i.d. capillary. The
      improved design incorporates an efficient method to preconcentrate a sample
      directly within the CE capillary followed by its electrophoretic separation and
      detection using a true zero dead-volume sheathless CE-MS interface. Testing of
      this novel CE-MS system showed its ability to characterize proteomic samples such
      as protein digests, in-gel-digested proteins, and hydrophobic peptides as well as
      to quantitate ICAT-labeled peptides.

PMID- 14588043
TI  - A copolymerized dodecacarborane anion as covalently attached cation exchanger in
      ion-selective sensors.
AB  - The traditional cation exchangers used in ion-selective electrodes and optodes
      are tetraphenylborate derivatives, which are generally adequate for most
      analytical applications but may in some cases suffer from decomposition by acid
      hydrolysis, oxidants, and light. Recently, halogenated dodecacarboranes were
      found to be improved cation exchangers in terms of lipophilicity and chemical
      stability. This forms the basis for the convenient covalent attachment of the
      cation exchanger to the polymeric backbone of the sensing material. This is a
      challenge that has not satisfactorily been solved and which is especially
      important in view of developing ultraminiaturized sensing arrays. Here, a C
      derivative of the closo-dodecacarborane anion (CB(11)H(12)(-)) with a
      polymerizable group was synthesized as a chemically stable cation exchanger. This
      new derivative was copolymerized with methyl methacrylate and decyl methacrylate
      (MMA-DMA) to fabricate a plasticizer-free polymer with cation-exchange
      properties. This polymer could be conveniently blended with traditional
      plasticized poly(vinyl chloride) or with noncrosslinked methacrylic polymers to
      give solvent cast films that appear to be clear and homogeneous and that could be
      doped with ionophores. Optode leaching experiments supported the covalent
      grafting of the carborane anions. Ion-selective membranes and optode thin films
      were evaluated in terms of response function, response time, and selectivity. In
      all cases, the new material exhibited behavior similar to free tetraphenylborate
      derivative-based membranes. As a result of these studies, an all-polymeric
      plasticizer-free calcium-selective membrane was fabricated on the basis of the
      covalently attached carborane, a recently introduced grafted calcium ionophore,
      and an MMA-DMA polymer matrix. The resulting ion-selective electrodes showed
      Nernstian response slopes and rapid response times, demonstrating that covalent
      grafting of all sensing components is a feasible approach to the development of
      ion sensors.

PMID- 14588044
TI  - Surfactant to dye binding degree-based methodology for the determination of ionic
      amphiphilic compounds.
AB  - A new analytical measurement parameter based on the effect of amphiphilic
      substances on the degree of binding of a surfactant to dye molecules, which
      induce the formation of surfactant premicellar aggregates, is presented. The
      theory for dye-surfactant intermolecular interactions in mixed surfactant
      systems, which assumes a mononuclear model for the formation of dye-induced
      premicellar aggregates, has been used to derive an expression that provides
      linear calibrations for the determination of amphiphilic compounds. The dye
      surfactant interactions involved have been investigated, and the variables
      affecting the measurement analytical parameter have been discussed. The
      analytical applicability of the surfactant-dye binding degree method is
      demonstrated by quantifying major anionic surfactants at the nanograms-per
      milliliter level and determining the total concentration of these amphiphilic
      substances in sewage samples (average recoveries ranged from 98 to 102%).

PMID- 14588045
TI  - Flow injection analysis of an ultratrace amount of arsenite using a Prussian blue
      modified screen-printed electrode.
AB  - We report here a new electrochemical method for the selective detection of
      ultratrace amount of arsenite (AsO(2)(-), As(3+)) using a Prussian blue-modified
      screen-printed electrode (designated as PBSPE) by flow injection analysis (FIA)
      in 0.1 M, pH 4 KCl/HCl carrier solution. The Prussian yellow/Prussian blue redox
      couple of the PBSPE was found to mediate the As(3+) oxidation. Various factors
      influencing the determination of As(3+) were thoroughly investigated in this
      study. Under the optimized FIA conditions, a linear calibration plot in the range
      of 50 nM-300 microM with a detection limit (S/N = 3) of 25 nM (i.e., 64.9 pg in
      20-microL loop) was observed at an operation potential of +0.6 V vs Ag/AgCl. The
      sensitivity was good enough to detect arsenite at levels lower than the current
      EPA standard. This modified electrode showed good resistance to interference from
      common ions, especially Cl(-), which is generally considered as a major
      interference in the determination of As(3+) by ICPMS. The practical utility of
      the PBSPE to detect As(3+) was demonstrated in "blackfoot" disease endemic
      village groundwater from the southwestern coast area of Taiwan (Pei-Men).

PMID- 14588047
TI  - Cylindrical compact thermal-cycling device for continuous-flow polymerase chain
      reaction.
AB  - A compact, thermal-cycling device for high-throughput continuous-flow polymerase
      chain reaction (PCR) has been developed, which consists of a flow-through
      capillary and a cylindrical heating-block assembly. A 3.5-m-long fused-silica
      capillary coils helically, with 33 turns, up around the 30-mm-diameter assembly
      of three equally divided thermostating copper blocks for melting, annealing, and
      extension. An injected PCR mixture undergoes one cycle of PCR each turn. A
      continuous-flow PCR of one sample and also a segmented-flow PCR of four different
      samples have been successfully demonstrated. The present device can easily evolve
      into a parallel-processing, multistation compact device and be modified to have
      real-time PCR capability. This solid-based compact PCR device, therefore, has a
      potentiality to be the format of choice when developed for a portable system.

PMID- 14588046
TI  - Enzyme-friendly, mass spectrometry-compatible surfactant for in-solution
      enzymatic digestion of proteins.
AB  - Improved in-solution tryptic digestion of proteins in terms of speed and peptide
      coverage was achieved with the aid of a novel acid-labile anionic surfactant
      (ALS). Unlike SDS, ALS solubilizes proteins without inhibiting trypsin or other
      common endopeptidases activity. Trypsin activity was evaluated in the presence of
      various denaturants; little or no decrease in proteolytic activity was observed
      in 0.1-1% ALS solutions (w/v). Sample preparation prior to mass spectrometry and
      liquid chromatography analysis consists of sample acidification. ALS degrades
      rapidly at low-pH conditions, which eliminates surfactant-caused interference
      with analysis. Described methodology combines the advantages of protein
      solubilization, rapid digestion, high peptide coverages, and easy sample
      preparation for mass spectrometry and liquid chromatography analyses.

PMID- 14588053
TI  - Who will lead the field beyond 2020?

PMID- 14588054
TI  - What works for people with mental retardation? Critical commentary on cognitive
      behavioral and psychodynamic psychotherapy research.

PMID- 14588055
TI  - Balancing choice with health considerations in residential environments.

PMID- 14588056
TI  - Lessons from the field: participatory action research in a family research
      project.

PMID- 14588057
TI  - Federal income payments and mental retardation: the political and economic
      context.
AB  - Federal income maintenance programs for people with mental retardation in the
      United States were described. Combined SSI and DI spending in fiscal year 2000
      totaled an estimated $20.6 billion for people with mental retardation. This
      population is particularly vulnerable to the vagaries of changing public policy
      and are particularly reliant upon public support. The relative importance of
      income programs in the lives of people with mental retardation is discussed and
      the changing role of federal social welfare policy with regard to these programs
      analyzed.

PMID- 14588058
TI  - Comprehensive approach toward improving oral hygiene at a state residential
      facility for people with mental retardation.
AB  - Poor oral hygiene is a problem for many people with mental retardation who live
      in state residential facilities. An integrated treatment approach to improve oral
      hygiene was designed and implemented. The program focused on increasing
      cooperation with daily oral care. We examined whether individualized oral care
      plans were more effective in improving the oral hygiene of people living in this
      facility than generalized staff training in oral care procedures. Oral hygiene
      ratings of 80 individuals were tracked over a one-year period and analyzed. A
      modest improvement was found for all people studied, with a greater improvement
      for those with individualized oral care plans. The need for follow-up data and
      procedures to ensure follow through of recommendations is emphasized.

PMID- 14588059
TI  - Participation in religious services by people with developmental disabilities.
AB  - In this qualitative study we look critically at the opportunity for participation
      in religious services for people with developmental disabilities from three
      perspectives: house managers (n = 4), church leaders (n = 6), and people with
      developmental disabilities residing in group homes (n = 25). Observations were
      also made at several church services attended by the group home residents.
      Results suggest that people with developmental disabilities want to go to church
      and enjoy religious worship. Their full inclusion in activities and developing
      friendships, however, appears to be quite limited due to the conflicting
      expectations of house managers and church leaders, the lack of transportation or
      support staff, and the stereotypical attitudes towards people with developmental
      disabilities.

PMID- 14588060
TI  - Continuum of intellectual disability: demographic evidence for the "forgotten
      generation".
AB  - Demographic features of Americans with mild intellectual disabilities were
      estimated in an analysis of the National Health Interview Survey. The cohort was
      compared to the population of the United States, persons with specific learning
      disabilities, and persons with mental retardation. Comparison on basic indices of
      adaptive functioning and SES suggest a large cohort of Americans who share many
      support needs and social and economic vulnerabilities with those labeled
      "mentally retarded." The combined prevalence of intellectual disability/mental
      retardation was estimated to be 1.27%. Implications are discussed in terms of the
      "forgotten generation" report of the 1999 President's Committee on Mental
      Retardation and evolving conceptions of mental retardation.

PMID- 14588061
TI  - Impacts of children with troubles on working poor families: mixed-method and
      experimental evidence.
AB  - Mixed-method and experimental data on working poor families and children with
      troubles participating in the New Hope anti-poverty experimental initiative in
      Milwaukee are described. Sixty percent of these families had at least one child
      who had significant problems (learning, school achievement and/or behavior, home
      behavior, retardation, other disabilities). Control group families with children
      who had troubles had more difficulties in sustaining their family routine than
      did New Hope experimental families. In the context of the many other challenges
      these parents face, adaptation to children with troubles does not stand out as
      sharply compared to middle-class European American families. There is less family
      adaptation specifically due to, or in response to, the troubled child, and more
      adaptation to the struggles of making ends meet.

PMID- 14588062
TI  - GISTs: from the molecular knowledge to the rational treatment.

PMID- 14588063
TI  - Characterization of GIST/GIPACT tumors by inmunohistochemistry and exon 11
      analysis of c-kit by PCR.
AB  - Gastrointestinal stromal tumors (GIST/GIPACT) are the most common mesenchymal
      tumors of the human gastrointestinal (GI) tract and are characterized by the
      constant immunohistochemical expression of CD117. In recent years, sporadic and
      germ line mutations in the c-kit gene have been described in GIST/GIPACT tumors,
      resulting in a constitutive activation of the gene. The most prevalent mutation
      is located in exon 11 of the c-kit gene, involved in the transcription of the
      juxta-membrane domain of the c-kit protein. There are conflicting reports with
      respect to the association between exon 11 mutations and the biological behavior
      of GIST/GIPACT tumors. This work studies eight patients with tumors diagnosed as
      GIST/GIPACT, both morphologically and immunohistochemically for CD117, CD34, a
      smooth muscle actin, desmin and S-100 protein primary antibodies. The DNA of the
      eight cases was also studied by PCR for mutation of exon 11 of the c-kit gene.
      All cases were CD117 positive, but only two showed mutation of exon 11. These
      last two cases did not show morphological characteristics of malignancy. The most
      aggressive case, with early death of the patient, did not show the mutation. In
      conclusion, there was no correlation between the mutation of exon 11 of the c-kit
      gene and the malignant behavior of GIST/GIPACT tumors in our series.

PMID- 14588064
TI  - Failure of endoscopic therapy in upper gastrointestinal hemorrhage due to
      duodenal ulcers.
AB  - OBJECTIVES: to evaluate the efficacy of endoscopic treatment in patients with
      upper gastrointestinal (UGIH) due to duodenal ulcer with high risk of persistent
      or recurrent bleeding and to determine the associated failure factors of this
      procedure. PATIENTS AND METHOD: three hundred and thirty-six patients with UGIH
      due to duodenal ulcer requiring endoscopic treatment were analyzed between
      January 1992 and December 2001. The patients were classified according to the
      endoscopic findings: a) patients with limited bleeding; and b) patients with
      persistent and/or recurrent bleeding due to therapeutic failure. The clinical
      guidelines followed in patients with endoscopic treatment failure were previously
      established in the internal protocol. The variables that obtained statistical
      significance in the univariate analysis were included in the logistic regression
      model to identify those with an independent predictive value for failure of the
      endoscopic treatment. RESULTS: mean age of the patients was 60 +/- 17 years, 271
      (81%) were male. Bleeding with severe hemodynamic affectation was detected in 82
      patients (24%). The most common location of the duodenal ulcer was on the
      anterosuperior part of the duodenal bulb (227 patients, 68%). In 43 patients
      (13%) the ulcer was larger than 2 cm. The bleeding stigmata were classified as:
      Forrest I in 125 (38%) and Forrest II in 211 (62%). It was initially reached in
      297 patients (88%). Twenty-two patients required emergency surgery (6,5%) and the
      global mortality rate was 3%. Severe hemodynamic affectation at admission (OR
      11.8, p>0.001), ulcers exceeding 2 cm (OR 6.95, p = 0.019) and the presence of
      active bleeding during endoscopy (Forrest I) (OR 3.55, p = 0.08) were the
      variables included in the multivariate analysis independently associated to
      endoscopic therapy failure. CONCLUSION: endoscopic therapy is an efficient
      treatment of upper gastrointestinal bleeding due to duodenal ulcer. By means of a
      clinical variable, the hemodynamic status and two endoscopies, bleeding stigmata
      and the size of the ulcer, a group of patients with high risk of endoscopic
      treatment failure can be selected.

PMID- 14588065
TI  - Clinical features and endoscopic progression of gastroesophageal reflux disease.
AB  - OBJECTIVES: 1. To determine the progression of endoscopic affectation in patients
      with gastroesophageal reflux disease (GERD). 2. To analyze the clinical
      parameters associated to grade IV of esophagitis, as well as the degree of
      endoscopic progression. MATERIAL AND METHODS: between 1996 and 2002, 692 patients
      with GERD have been followed prospectively (66% men and 33% women, with a mean
      age of 50.7 years). All were submitted to initial upper endoscopy, without
      treatment, and different clinical parameters associated to grade IV esophagitis
      were analyzed. During follow up, a new endoscopy was repeated in the event of
      symptomatic relapse, comparing the new findings with those of the initial
      exploration. RESULTS: the initial endoscopy did not reveal signs of esophagitis
      in 49% of the patients. Grade I 11.2%, grade II 22%, grade III 8.1% and grade IV
      8.7%. Multivariant analysis showed that advanced age (p <0.01), male sex (p
      <0.03), smoking (p <0.02) and absence of infection due to Helicobacter pylori (p
      <0.02) were independent factors associated to grade IV esophagitis. Throughout
      follow up, patients without esophagitis did not show evidence of esophagitis in
      successive endoscopies, and a higher grade was found in only 3 of the patients.
      CONCLUSIONS: the endoscopy did not reveal signs of esophagitis in approximately
      half of the patients. Advanced age, male sex, smoking and absence of Helicobacter
      pylori are risk factors associated with severe stages of esophagitis. Patients
      with reflux without esophagitis did not develop inflammatory disorders during
      follow-up, while those with esophagitis remained in the stage of the initial
      diagnosis.

PMID- 14588066
TI  - Practical guide of anal incontinence.

PMID- 14588067
TI  - Acute cholecystitis as a complication following percutaneous ethanol injection of
      a hepatocellular carcinoma.
AB  - Percutaneous ethanol injection is a useful option in the treatment of
      hepatocellular carcinoma which are not amenable to resection or transplantation.
      We describe a case of cholecystitis and tumour infiltration of the gallbladder
      after percutaneous ethanol injection, a complication not previously described in
      literature. The patient was a 70-year-old woman with a history of asymptomatic
      HCV+ hepatopathy and a 6 cm hepatocellular carcinoma nodule in segment V which
      had been treated two months before by percutaneous ethanol injection in another
      center. She attended our center due to febrile syndrome. Imaging studies
      suggested cholecystitis with an abscess on the wall of the gallbladder, purulent
      material obtained by means of a CT-guided puncture. Surgery revealed purulent and
      neoplasic material inside the gallbladder, with tumor invasion of the posterior
      wall; a partial cholecystectomy was therefore performed and a drainage inserted.
      The patient showed no post-operative complications and was discharged after seven
      days. CONCLUSION: we believe that the percutaneous ethanol injection of
      hepatocellular carcinomas located close to the gallbladder may occasionally lead
      to complications in the form of cholecystitis with neoplasic infiltration of the
      gallbladder. A case of cholecystitis secondary to radiofrequency treatment of a
      similarly-located tumor has previously been described and, therefore, the use of
      percutaneous local destructive treatments for tumors close to the gallbladder
      would seem unadvisable.

PMID- 14588068
TI  - Intestinal obstruction caused by omphalomesenteric duct remnant: usefulness of
      laparoscopy.
AB  - The anomalies related to omphalomesenteric duct remnant constitute an uncommon
      cause of intestinal obstruction, of which Meckel"s diverticulum and its variants
      represent the most important clinical presentation. In most cases they are
      asymptomatic and usually affect young patients. When symptomatic, they usually
      present episodes of gastrointestinal bleeding or acute abdomen syndromes caused
      by strangulation of intestinal loops as a result of fibrous intraabdominal
      remnants or inflammation produced by the diverticulum. In most cases, the
      unexpected presence of these alterations makes intraoperative diagnosis
      necessary. Treatment is surgical and consists in exeresis of the diverticulum or
      the fibrous band causing the clinical picture. We report two cases of persistence
      of the vitelline duct resolved by laparoscopic approach.

PMID- 14588069
TI  - Gastric tumor evaluated by endoscopic ultrasonography.

PMID- 14588070
TI  - [Acute hepatitis and minocycline].

PMID- 14588071
TI  - [Sclerotherapy in the treatment of achalasia].

PMID- 14588072
TI  - Effects of age and physical fitness on microcirculatory function.
AB  - Sedentary aging is associated with endothelial dysfunction and nitric oxide (NO)
      impairment. The aim of the present study was to assess the effects of regular
      physical exercise on nitrite/nitrate (NOx) concentrations and microcirculatory
      function in older men compared with young individuals. We measured NOx plasma
      concentrations and baseline and stimulated skin blood flow (SBF) by laser Doppler
      flowmetry in 39 male athletes [range, 22-72 years; maximal oxygen consumption
      (VO2max), 60.0 +/- 4.7 ml.min(-1).kg of body weight(-1) (mean +/- S.D.)] and 45
      age- and sex-matched sedentary controls (VO2max, 38.0 +/- 7.1 ml.min(-1).kg of
      body weight(-1)). NOx concentrations were higher in athletes than in controls
      (50.4 +/- 16.3 compared with 39.0 +/- 15.4 micromol/l; P<0.005), whereas baseline
      SBF was comparable. Hand SBF after heating and ischaemia and foot SBF after
      heating were higher in athletes (P<0.0001) than in controls. By comparing the
      lowest and the highest tertile of age, sedentary young subjects had higher NOx
      concentrations than sedentary older subjects (43.3 +/- 13.4 compared with 31.8 +/
      12.2 micromol/l respectively; P<0.05). Exercise abolished this difference (49.1
      +/- 9.6 micromol/l for young subjects and 52.1 +/- 11.5 micromol/l for older
      subjects; not significant). Resting SBF was similar in all the subgroups, but
      stimulated SBFs were lower in both subgroups of untrained compared with trained
      subjects. NOx concentrations were positively correlated with VO2max (r=0.46,
      P<0.001). Stimulated SBFs were correlated with NOx (r>0.30, P<0.05). These
      findings show that chronic exercise may improve endothelial function in older
      (and young) men, probably by increasing NO availability.

PMID- 14588074
TI  - The role of protein elongation factor eEF1A2 in ovarian cancer.
AB  - Frequent gains of chromosome 20q12-13 in ovarian tumors indicate that at least
      one important oncogene is found at that locus. One of the genes there is EEF1A2,
      which maps to 20q13.3 and encodes protein elongation factor eEF1A2. This review
      will focus on recent evidence indicating that EEF1A2 is an important ovarian
      oncogene and that the protein elongation network can activate tumorigenesis and
      inhibit apoptosis.

PMID- 14588075
TI  - Enhancement of Tissue Expansion by Calcium Channel Blocker: A preliminary study.
AB  - BACKGROUND: Reconstruction of the defects after surgical resection of tumors is
      one of the important issues in surgical oncology. It is essential that the defect
      should be covered with a tissue quite similar to the original one and is best
      achieved by harvesting tissue from an area adjacent to the defect. Tissue
      expansion is one of the most frequently used reconstructive techniques. A number
      of studies evaluated blood circulation, capsule formation, tissue tolerance,
      histomorphological changes and complications of expander placement. However, only
      a few attempted to enhance tissue expansion. This study we aimed to evaluate
      verapamil, a calcium channel blocker, to enhance tissue expansion. MATERIAL AND
      METHOD: Twelve New Zealand rabbits weighing between 900 gm and 1200 gm were
      assigned into study and control groups. High volume expanders (100, 200 or 300
      cc) were placed into the subcutaneous tissue. Rabbits in the study group received
      verapamil. Expanders in the control group were inflated every three days to
      achieve same pressure as the study group. The size of the flaps was assessed by
      applying pressure on tip of the flap to demonstrate the contraction.
      Histopathological examinations were performed. RESULTS: By administering liquid
      earlier and more quickly less flap retraction was observed in the study group. In
      the control group expanders were exposed in two rabbits while no complication
      occurred in the study group. Following extraction of the expanders, the flaps
      were elevated and less retraction was observed in the study group compared to
      controls. CONCLUSION: Verapamil is safe when used topically and provides less
      retracted flaps. It can be suggested that verapamil acts on the myofibroblasts in
      the capsule around tissue expanders and thus increases efficiency of the
      expanders.

PMID- 14588077
TI  - Perspectives on advance directives in Japanese society: A population-based
      questionnaire survey.
AB  - BACKGROUND: In Japan, discussion concerning advance directives (ADs) has been on
      the rise during the past decade. ADs are one method proposed to facilitate the
      process of communication among patients, families and health care providers
      regarding the plan of care of a patient who is no longer capable of
      communicating. In this paper, we report the results of the first in-depth survey
      on the general population concerning the preferences and use of ADs in Japan.
      METHOD: A self-administered questionnaire was sent via mail to a stratified
      random sampling of 560 residents listed in the residential registry of one
      district of Tokyo, Japan (n = 165,567). Association between correlating factors
      and specific preferences toward ADs was assessed using contingency table
      bivariate analysis and multivariate regression model to estimate independent
      contribution. RESULTS: Of the 560 questionnaires sent out, a total of 425
      participants took part in the survey yielding a response rate of 75.9 %. The
      results of the present study indicate that: 1) the most important components to
      be addressed are the specifics of medical treatment at the end of life stage and
      disclosure of diagnosis and prognosis; 2) the majority of participants found it
      suitable to express their directives by word to family and/or physician and not
      by written documentation; 3) there is no strong need for legal measures in
      setting up an AD; 4) it is permissible for family and physician to loosely
      interpret one's directives; 5) the most suitable proxy is considered to be a
      family member, relative, or spouse. Multivariate analysis found the following
      five factors as significantly associated with preferences: 1) awareness regarding
      living wills, 2) experience with the use of ADs, 3) preferences for end-of-life
      treatment, 4) preferences for information disclosure, and 5) intentions of
      creating a will. CONCLUSIONS: Written ADs might be useful in the Japanese setting
      when the individual either wishes: 1) to not provide a lot of leeway to
      surrogates and/or caregivers, and/or 2) to ensure his or her directives in the
      cases of terminal illness, brain death, and pain treatment, as well as regarding
      information disclosure.

PMID- 14588078
TI  - Pain and disability reported in the year following a distal radius fracture: a
      cohort study.
AB  - BACKGROUND: Distal radius fractures are a common injury that cause pain and
      disability. The purpose of this study was to describe the pain and disabilities
      experienced by patients with a distal radius fracture in the first year following
      fracture. METHODS: A prospective cohort study of 129 patients with a fracture of
      the distal radius was conducted. Patients completed a Patient-rated Wrist
      Evaluation at their baseline clinic visit and at 2, 3, 6 and 12 months following
      their fracture. The frequency/severity of pain and disabilities reported was
      described at each time point. RESULTS: The majority of patients experienced mild
      pain at rest and (very) severe high levels of pain with movement during the first
      two-months following distal radius fracture. This time is also associated with
      (very) severe difficulty in performing specific functional activities and
      moderate to severe difficulty in four domains of usual activity. The majority of
      recovery occurred within six-months, but symptoms persisted for a small minority
      of patients at one-year following fracture. Patients had the most difficulty with
      carrying ten pounds and pushing up from a chair. Resumption of usual personal
      care and household work preceded, and was more complete, than work and
      recreational participation. CONCLUSIONS: This study demonstrated that the normal
      course of recovery following a distal radius fracture is one where severe
      symptoms subside within the first two-months and the majority of patients can be
      expected to have minimal pain and disability by six-months following fracture.
      This information can be used when planning interventions and assessing whether
      the progress of a patient is typical of other patients.

PMID- 14588080
TI  - Management of chronic hepatitis B in an HIV-positive patient with 3TC-resistant
      hepatitis B virus.
AB  - Chronic viral hepatitis has emerged as one of the leading causes of morbidity and
      mortality among HIV-positive patients. These individuals are at risk for
      aggressive chronic active hepatitis, cirrhosis, and hepatocellular carcinoma, and
      eventually, death. Currently available therapies for hepatitis B are limited and
      include interferon-alpha, lamivudine (3TC), and adefovir. Tenofovir (TDF), a
      recently approved drug for the treatment of HIV, is also active against hepatitis
      B. We report the case of a HIV-positive patient with liver cirrhosis secondary to
      chronic hepatitis B virus (HBV) with evidence of resistance to 3TC. The patient
      was initially accepted as a liver transplant candidate. However, when TDF was
      added to his treatment, a remarkable virologic and histopathologic improvement
      was achieved. The patient was subsequently removed from the liver transplant
      program and has not suffered from any further hepatic complications.

PMID- 14588079
TI  - Effects of non-steroidal anti-inflammatory drugs on cancer sites other than the
      colon and rectum: a meta-analysis.
AB  - BACKGROUND: Observational studies have consistently shown that aspirin and non
      steroidal anti-inflammatory drug (NSAID) use is associated with a close to 50%
      reduced risk of colorectal cancer. Studies assessing the effects of NSAIDs on
      other cancers have shown conflicting results. Therefore, we conducted a meta
      analysis to evaluate the relationship between NSAID use and cancer other than
      colorectal. METHODS: We performed a search in Medline (from 1966 to 2002) and
      identified a total of 47 articles (13 cohort and 34 case-control studies).
      Overall estimates of the relative risk (RR) were calculated for each cancer site
      using random effects models. RESULTS: Aspirin use was associated with a reduced
      risk of cancer of the esophagus and the stomach (RR, 0.51; 95%CI (0.38-0.69), and
      0.73; 95%CI (0.63-0.84)). Use of NSAIDs was similarly associated with a lower
      risk of esophageal and gastric cancers (RR,0.65; 95% CI(0.46-0.92) and RR,0.54;
      95%CI (0.39-0.75)). Among other cancers, only the results obtained for breast
      cancer were fairly consistent in showing a slight reduced risk among NSAID and
      aspirin users (RR, 0.77; 95%CI (0.66-0.88), and RR, 0.77; 95%CI (0.69-0.86)
      respectively)). CONCLUSIONS: The results of this meta-analysis show that the
      potential chemopreventive role of NSAIDs in colorectal cancer might be extended
      to other gastrointestinal cancers such as esophagus and stomach. Further research
      is required to evaluate the role of NSAIDs at other cancers sites.

PMID- 14588081
TI  - Correlation between lopinavir plasma levels and lipid abnormalities in patients
      taking lopinavir/ritonavir.
AB  - Lopinavir (LPV)/ritonavir (RTV) used in combination, is a potent antiretroviral
      drug. However, its benefit is limited by its inherent effect on lipid metabolism,
      causing dislypemia in a large proportion of treated patients. Fasting
      triglyceride (TG) and cholesterol levels were assessed in 126 HIV-infected
      patients who initiated salvage therapy based on LPV/RTV. Both TG and cholesterol
      significantly increased from baseline to month 3. A positive correlation was
      found between the percentage increase in TG and LPV trough levels (r = 0.32; p =
      0.003). Moreover, patients with TG elevations above the median (27%) showed
      higher LPV Ctrough levels than those with lower TG elevations (7.1 vs. 4.7
      microg/ml, p = 0.004). In contrast, no correlation was found between LPV Ctrough
      and increases in cholesterol levels. Cholesterol elevations were positively
      correlated with RTV Ctrough concentrations (r = 0.32; p = 0.003).

PMID- 14588082
TI  - AIDS incidence and mortality in a hospital-based cohort of HIV-1-seropositive
      patients receiving highly active antiretroviral therapy in Sao Paulo, Brazil.
AB  - Brazilian AIDS and HIV-1-seropositive patients have had free access to highly
      active antiretroviral therapy (HAART) since November 1996. Although secondary
      data based on official mortality statistics indicate a sharp decrease in AIDS
      mortality, few if any studies tried to estimate the prognosis for patients with
      HIV who have been followed from the beginning of the HAART era. An observational
      study, with retrospective and prospective components, was done in 233 adult HIV-1
      infected subjects who were recruited in the last 10 years at the outpatient
      sector of the Secondary Immunodeficiencies Clinic of the Department of
      Dermatology, Hospital das Clinicas da FMUSP, Sao Paulo, Brazil. The definition of
      AIDS followed the guidelines issued by the Centers for Disease Control (CDC) in
      1987. One hundred sixty patients were asymptomatic, 46 had AIDS, 24 had AIDS
      related complex, and 3 presented with acute infection at study entry. Twenty-nine
      (18%) of the asymptomatic subjects developed AIDS during follow-up, with 5 (3%)
      deaths. Among the 46 AIDS cases at entry, 7 (17%) died during follow-up. Thus, a
      total of 12 people (5.2%) died of AIDS in this cohort over a mean follow-up of
      5.2 years and 24 people were lost to follow-up (10.3%). Ninety percent of the
      survivors were on combined therapy (82% with 3 or more drugs, and 8% with 2
      drugs), while 10% were not taking antiretrovirals. People with AIDS at entry were
      5 times more likely to die during this period compared to patients who were
      asymptomatic at entry (p = 0.006). Women showed better outcomes than men,
      reflecting differences in CD4+ T-cell counts at study entry. All but 1 patient
      progressed to AIDS during the pre-HAART era (before 1996). In spite of its recent
      decline, mortality from AIDS-related conditions remains an important public
      health issue.

PMID- 14588084
TI  - Temporal trend and factors associated with late HIV diagnosis in Hong Kong, a low
      HIV prevalence locality.
AB  - We studied the temporal trend of late HIV diagnosis and its determinants in Hong
      Kong. Three surrogate markers were used to proxy late diagnosis: AIDS within 3
      months of HIV diagnosis, CD4 < 200/microL at HIV, and diagnosis at hospital. From
      1984 to 2000, 1530 nonperinatal HIV infections and 495 patients with AIDS were
      reported. Overall, 23.9% to 52.1% of the patients were late presenters according
      to the three surrogates. There was no improvement in late diagnosis in the highly
      active antiretroviral therapy (HAART) era (1997-2000) compared to the pre-HAART
      era (1984-1996). Gender, ethnicity, age, and HIV exposure category were
      significant factors of late diagnosis on univariate analysis. On multivariate
      analysis, a lower risk of late diagnosis per all 3 surrogates was observed in men
      having sex with men (ranges of adjusted odds ratio [OR] [95% confidence interval
      [CI], 0.32-0.67 [0.21-0.91]) whereas the reverse was found for patients 35 years
      of age or older (ranges of adjusted ORs [95% CI], 1.62-2.80 [1.30-3.60]). In
      addition, male gender and Chinese ethnicity were associated with higher chance of
      having CD4 < 200/microL at HIV. The persistent trend of late HIV diagnosis in
      Hong Kong deserves attention. Strategies targeting infected people to enhance
      early HIV testing are needed, especially for those with risk factors of late
      diagnosis.

PMID- 14588083
TI  - Sexual activities of patients with STDs in the interval between noticing symptoms
      and presenting for treatment.
AB  - Examining the patterns of and reasons for sexual behaviors of patients with
      sexually transmitted diseases (STDs) while symptomatic may help to develop
      effective prevention strategies for both STDs and AIDS. However, little is known
      about patients' sexual activities after noticing STD symptoms in China, where
      AIDS and STDs are spreading rapidly. We conducted a cross-sectional study at four
      STD clinics in Hefei, China. Patients' reported sexual activities were queried,
      using a tape recorder and earphones. A consecutive sample of 406 male patients
      with STDs were interviewed. One hundred sixty-four (40%) men reported having sex
      after having STD symptoms; 45% were married, 27% were single, and 47% cohabiting
      or divorced. Their sex partners included spouses, girlfriends, and prostitutes.
      Only 10% of patients with STDs who had sex after noticing STDs reported
      frequently using condoms or using them for every act of sex. Approximately 60%
      had never used a condom. Logistic regression analysis indicated that having sex
      after noticing STD symptoms was associated with lower education, having a
      previous STD episode, having low HIV/STD knowledge, and having other urethral
      discharge not caused by C. trachomatis or gonorrhea. Our findings suggest that
      male patients with STDs may serve as a bridge population linking the STD, and
      potentially, HIV epidemic from individuals at higher risk to the general
      population. Intervention programs including health education and condom promotion
      need to target both those at high risk and those at apparently lower risk.

PMID- 14588085
TI  - Medication adherence practices of HIV/AIDS case managers: a statewide survey in
      North Carolina.
AB  - The primary objective of this study was to examine the adherence-related
      practices and attitudes of HIV/AIDS case managers in North Carolina. All North
      Carolina HIV/AIDS case managers (n = 111) employed by agencies that were state
      certified to provide HIV case management were sent an adherence counseling
      survey. Negative binomial regression was used to examine the relationship of case
      managers' characteristics and attitudes with their medication adherence
      counseling practices. Of the 94 HIV/AIDS case managers who responded to the
      survey, the majority (65%) reported discussing medications with almost every
      client. The adherence-related behaviors that case managers most frequently
      provided were related to monitoring medication usage rather than providing
      medication instruction. Most case managers believed that medication adherence
      counseling is part of their role (77%); however, a substantial minority, (36%)
      did not believe that their adherence counseling skills were adequate.
      Multivariate analysis revealed that case managers who provided more adherence
      counseling services reported greater confidence in their adherence counseling
      skills, believed that adherence counseling is a HIV/AIDS case management role,
      and had a higher proportion of substance-abusing clients in their caseload. The
      adherence counseling activities of HIV/AIDS case managers can potentially
      supplement the counseling provided by other health professionals and promote
      greater adherence to medications. However, variability in perceived skills and
      adherence-related activities suggests that the role of case managers in
      medication adherence counseling needs to be better defined and appropriate
      training provided to meet the expectations of this role.

PMID- 14588086
TI  - Resistance data on 908.

PMID- 14588087
TI  - HIV testing device protects identity.

PMID- 14588088
TI  - Drug therapy in ARV-experienced patients. Interview by Vicki Glaser.

PMID- 14588089
TI  - Hodgkin's lymphoma as a cause of fever of unknown origin in HIV infection.
AB  - The risk of Hodgkin's lymphoma is increased in HIV-infected patients. In these
      patients Hodgkin's lymphoma is an aggressive disease with poor clinical outcome.
      Complete remission and survival rates are far below that reported in HIV
      uninfected population. Since the widespread use of highly active antiretroviral
      therapy, malignancies are the major cause of mortality in HIV-infected patients.
      We report a case of a 29-year-old HIV-positive male who presented with fever of
      unknown origin, pancytopenia, and hemophagocytic syndrome. The diagnosis of
      Hodgkin's lymphoma with bone marrow involvement was made on bone marrow biopsy, 5
      months after the onset of fever. The patient was treated with chemotherapy and
      achieved a complete remission. Relapse occurred 28 months later and he died 31
      months after initial diagnosis. Prolonged fever is frequently observed in HIV
      infected patients and could represent a diagnostic challenge. Infectious diseases
      are the most common causes, however lymphomas are the third most common cause of
      fever of unknown origin in HIV disease. This case illustrates the difficulties in
      accurately diagnosing Hodgkin's lymphoma in patients presenting with prolonged,
      unexplained fever, and emphasizes the use of bone marrow biopsy to confirm
      Hodgkin's lymphoma, particularly if cytopenia and hemophagocytic syndrome are
      present.

PMID- 14588091
TI  - Neurologic consequences of HIV infection in the era of HAART.
AB  - In this brief review, we present a summary of the clinical presentation of HIV
      associated dementia (HAD), HAD in the highly active antiretroviral therapy
      (HAART) era, the immunopathogenesis of HAD, and the possible role of a recently
      described novel macrophage-derived protein in HAD. Different aspects of the
      clinical presentation of HAD will be reviewed as well as the results of recent
      autopsy studies demonstrating that although HAART dramatically decreased the
      incidence of opportunistic infections and malignancies in the central nervous
      system, it has reduced but not eliminated HIV encephalopathy. This suggests a
      direct cytopathic effect of HIV on neuronal tissue. Consequently, the
      immunopathogenesis of HAD and the role of neurotoxins produced by brain
      macrophages and microglial cells will be reviewed including the possible role of
      a recently cloned macrophage-derived proapoptotic factor, soluble HIV apoptotic
      protein (SHIVA) identified in our laboratory. HAART therapy reduces the incidence
      of opportunistic infections, the direct pathogenic effect of HIV, especially on
      neuronal tissue, may become of increasing importance.

PMID- 14588090
TI  - Kidney and liver transplantation in HIV-infected patients: case presentations and
      review.
AB  - Until recently, HIV-infected patients have been excluded from consideration for
      solid organ transplantation. The relatively high mortality rates among HIV
      infected transplant recipients observed in the era prior to the use of highly
      active antiretroviral therapy (HAART), coupled with long waiting times for
      cadaveric organs, made it difficult to support organ transplantation in this
      patient group. However, in response to the marked reductions in morbidity and
      mortality associated with HIV infection, several transplant centers have
      developed pilot studies or revised their clinical criteria to allow
      transplantation in this group of patients. We describe two cases, one kidney and
      one liver transplant recipient, and review the major clinical and research issues
      related to this topic. Reports of transplantations in the pre-HAART era highlight
      two important findings. First, some HIV-infected transplant recipients did very
      well with long survival periods. However, overall progression to AIDS and death
      appeared accelerated. We recently reported on our preliminary experience with 45
      selected transplant recipients in the HAART era. One-year patient survival rates
      were similar to unmatched survival data from the United Network for Organ Sharing
      (UNOS) database. Median CD4+ T-cell counts remained stable in the follow-up
      period compared to pretransplant. HIV-1 RNA nearly uniformly continued to be
      suppressed below the limits of detection. Preliminary data are promising and
      support the current efforts to evaluate patient and graft survival among HIV
      infected transplant recipients and to explore the mechanisms underlying the many
      potential complications of transplantation in this population.

PMID- 14588092
TI  - Patterns of adherence to antiretrovirals: why adherence has no simple measure.
AB  - The goal of this study was to explore patterns and explanations of adherence to
      antiretroviral therapies from the patient's perspective. It consisted of 78 in
      depth interviews with patients attending an HIV clinic in New Orleans, Louisiana,
      to whom combination therapy had been prescribed. Interviews explored patient's
      definitions of adherence, beliefs about consequences of nonadherence, reasons for
      current and past adherence behavior, and contextual issues such as drug and
      alcohol use and social support. Respondents reported nine distinct patterns of
      adherence, which they perceived to have different consequences and causes. These
      patterns hid variations because respondents could have more than one pattern
      simultaneously and patterns were not stable over time. Although there are gold
      standards for adherence measurement, such as directly observed therapy, these
      measurements are most frequently used to classify respondents as adherers or
      nonadherers based on whether they take a certain percentage of their medication.
      Such a categorization is simplistic and does not reflect the complexity of
      adherence patterns.

PMID- 14588093
TI  - Optimizing care for African-American HIV-positive patients.
AB  - The African-American community has been disproportionately affected HIV/AIDS, as
      noted by higher reported rates of HIV infection, higher proportion of AIDS cases,
      and more deaths caused by complications of AIDS than whites and other ethnic
      groups. In addition, epidemiologic trends suggest that African Americans with HIV
      infection are more often diagnosed later in the course of HIV disease than
      whites. Numerous reasons account for this disparity, including the lack of
      perception of risk and knowledge about HIV transmission as well as a delays in
      HIV testing and diagnosis in the African-American community. Understanding the
      important considerations in the management of HIV infection in the African
      American patient may create awareness among health care professionals and broaden
      the knowledge of HIV-infected patients within the African-American community.

PMID- 14588094
TI  - Warning issued on non-response rates.

PMID- 14588095
TI  - Bathhouse testing urged again.

PMID- 14588096
TI  - Thyroid related dissertations.

PMID- 14588097
TI  - Polymorphism in the transmembrane region of the major histocompatibility complex
      class I chain-related gene A: association of five GCT repetitions with Graves'
      disease in children.
AB  - Graves' disease is an autoimmune disease involving a complex interplay of
      multiple genetic and environmental influences. An association between the
      disorder and the major histocompatibility complex (MHC; human leukocyte antigen
      [HLA]) region has long been reported. The major histocompatibility complex class
      I chain-related gene A (MICA) has a triplet repeat polymorphism in the
      transmembrane region consisting of six alleles. For this study, the polymorphism
      in question was analyzed for 129 unrelated children with Graves' disease (97
      girls and 32 boys, 10.0 +/- 3.0 years of age) and 396 randomly selected,
      unrelated subjects (205 females, 191 males, 8.4 +/- 13.5 years of age). The
      frequencies of genotype A5/A5 and A5/A5.1 were significantly higher in patients
      than in controls (relative risk [RR] = 2.49, 95% confidence interval [CI] 1.52
      4.10, p = 0.00024, pc = 0.0035 and RR = 2.13, 95% CI 1.31-3.47, p = 0.0020, pc =
      0.030; respectively). The frequency of genotype A5.1/A5.1 was significantly lower
      in patients than in controls (RR = 0.09, 95% CI 0.01-0.66, p = 0.0030, pc =
      0.044). Allele frequency for allele A5 was significantly higher for children with
      Graves' disease compared to controls (RR = 2.12; 95% CI = 1.59-2.82; p = 1.9 x
      10(-7); pc = 9.5 x 10(-7)). This study demonstrates that MICA allele A5 confers
      the risk for Graves' disease.

PMID- 14588098
TI  - Peroxisome proliferator-activated receptor-gamma gene expression in orbital
      adipose/connective tissues is increased during the active stage of Graves'
      ophthalmopathy.
AB  - The mechanisms involved in the increase of orbital retro-ocular adipose tissue
      that occurs in Graves' ophthalmopathy (GO) are still unclear. In this condition,
      the orbital tissue shows glycosaminoglycans deposition produced by activated
      fibroblasts capable of undergoing adipocytic differentiation. Many genes are
      involved in adipogenic mechanisms including the transcription factor peroxisome
      proliferator-activated receptor-gamma (PPAR-gamma). We evaluated the level of
      expression of the PPAR-gamma gene in normal and GO orbital adipose/connective
      tissue specimens using a quantitative and sensitive reverse transcription (RT)
      competitive polymerase chain reaction (PCR) assay. Our results show that the
      expression of PPAR-gamma was significantly greater in adipose/connective tissue
      from patients in the active stage of GO than in controls (150.8 +/- 103.9 and
      24.0 +/- 4.9 amol/micro g of total RNA respectively, p < 0.05), while there was
      no significant difference between patients with inactive GO (58.8 +/- 40.6
      aM/microg total RNA) and controls. These results suggest that increased PPAR
      gamma gene expression in the active stage of GO may be dependent on the
      inflammatory process in this disease. We speculate that the increased orbital fat
      tissue observed in GO may be a consequence of the anti-inflammatory PPAR-gamma
      action.

PMID- 14588099
TI  - Glycosaminoglycans provide a binding site for thyroglobulin in orbital tissues of
      patients with thyroid-associated ophthalmopathy.
AB  - The presence of thyroglobulin (Tg) in orbital tissues of patients with thyroid
      associated ophthalmopathy (TAO) supports a role of Tg in TAO pathogenesis. To
      search for Tg-binding sites in orbital tissues, because Tg is a heparin-binding
      protein, we investigated its binding to glycosaminoglycans (GAGs) that are
      abundant in orbital tissues: chondroitin sulfate B (CSB) and C (CSC) and
      hyaluronic acid (HA). Both in solid phase and solution phase assays purified
      human Tg bound to GAGs. In solid-phase assays, binding was increased by
      coincubation with heparin or GAGs in solution, or with an antibody against a Tg
      heparin-binding sequence (Arg2489-Glu2503), possibly suggesting crosslinking of
      Tg molecules induced by GAGs or by the presumably bivalent antibody. Orbital
      tissue extracts from TAO patients that contained Tg were subjected to high-salt
      treatment, which resulted in separation of Tg from GAGs, as observed by column
      chromatography. After separation from GAGs, the Tg in orbital tissue extracts
      acquired the ability to bind to immobilized CSB, and heparin enhanced binding,
      resembling the findings with purified human Tg. Therefore, we conclude that GAGs
      provide binding sites for Tg in orbital tissues, which may explain the presence
      of Tg in orbital tissues of patients with TAO.

PMID- 14588100
TI  - Serum thyroglobulin measurements with a high sensitivity enzyme-linked
      immunosorbent assay: is there a clinical benefit in patients with differentiated
      thyroid carcinoma?
AB  - Serial serum thyroglobulin (Tg) measurements with a highly sensitive enzyme
      linked immunosorbent assay (ELISA; functional sensitivity 0.03 ng/mL) in 126
      patients (Tg autoantibody negative) with treated differentiated thyroid cancer
      (DTC) are described. At the beginning of the retrospective study, all 126
      patients were in remission and Tg was detectable by ELISA in 92 (73%; range, 0.03
      0.8 ng/mL). Over the following 4-year period, Tg levels remained essentially
      unchanged (i.e., any increases were less than 2 times the Tg level at the start
      of the study) in 121 of 126 (96%) and all 121 patients remained well. In 5
      patients, Tg levels increased to more than 2 times the starting Tg level over the
      study period and in 4 of these 5, there was recurrence of DTC. The fifth patient
      in this group remains well as evidenced by extensive diagnostic imaging, although
      his serum Tg level continues to increase and can be stimulated by thyrotropin
      (TSH). Our results suggest that serial measurements of low levels of Tg by ELISA
      in treated patients with DTC enable detection of recurrence (without using TSH
      stimulation) 6-12 months earlier than would have been possible using a
      conventional Tg immuno-radiometric assay (IRMA). A prospective study is now
      needed to confirm these observations.

PMID- 14588101
TI  - Evaluation of quantitative measurement of thyroglobulin mRNA in the follow-up of
      differentiated thyroid cancer.
AB  - Detection of thyroid cancer by thyroglobulin (Tg) assay in peripheral blood is
      useful in the absence of residual thyroid tissue, but it requires thyrotropin
      stimulation for maximal sensitivity and is affected by circulating
      antithyroglobulin antibodies. To avoid these drawbacks, thyroglobulin mRNA (Tg
      mRNA) assay in circulating blood has been proposed. Initial studies showed that
      Tg mRNA assay was more positive in patients with metastasis than in cured
      patients. Further studies showed controversial data. We measured Tg mRNA in 26
      patients undergoing levothyroxine (LT(4)) suppressive therapy after total
      thyroidectomy for thyroid cancer and in 11 controls. The stage of the cancer was
      defined according to the findings of the latest whole-body (131)I scan and serum
      Tg performed under LT(4) withdrawal. Patients were classified as cured (negative
      scan, negative stimulated Tg, 8 patients), with metastasis (positive scan in
      extrathyroid bed regions, positive Tg, 7 patients), with thyroid remnants
      (positive scan in thyroid bed, positive Tg, 8 patients), and discordant cases
      (negative scan, positive Tg, 3 patients). RNA was extracted from blood and
      analyzed by quantitative reverse transcription-polymerase chain reaction (RT-PCR)
      using two sets of primers and internal probes specific for Tg mRNA. This method
      allowed the detection of Tg mRNA in thyroid biopsies. Tg mRNA was undetectable in
      all control subjects and in all patients with cured cancer, positive in 1 of 8
      patients with thyroid remnants, and in only 1 of 7 patients with metastasis. In
      conclusion, our data do not support the usefulness of Tg mRNA measurements in
      blood for monitoring thyroid cancer.

PMID- 14588102
TI  - Postpartum maternal iodine status and the relationship to neonatal thyroid
      function.
AB  - Iodine deficiency in the postpartum period has the potential to affect neonatal
      neuropsychointellectual development. We performed a cross-sectional study
      involving 50 postpartum women and their neonates, measuring maternal urine
      iodine, breast milk iodine, and neonatal thyroid stimulating hormone (TSH), and
      examining their interrelationships. Women were studied at a median (range) of 4
      (3-9) days postpartum. Moderate to severe iodine deficiency (defined by urine
      iodine concentration < 50 microg/L) was found in 29 of the 50 subjects (58%). The
      median +/- standard deviation (SD) urine iodine was 46.8 +/- 28.5 microg/L and
      the mean urine iodine expressed in micrograms per gram of creatinine was 86.6 +/-
      45.6. The median (range) breast milk iodine was 84.0 microg/L (25.0-234.0).
      Breast milk iodine was significantly correlated with urine iodine in micrograms
      per gram of creatinine (r = 0.52, p < 0.001) but not with urine iodine measured
      in micrograms per liter (r = 0.19, p = 0.2). Six percent of neonates had whole
      blood TSH values of greater than 5 mIU/L. Neonatal TSH levels were positively
      correlated with higher breast milk iodine (r = 0.42, p = 0.003). There was no
      significant correlation between neonatal TSH levels and the mother's urine iodine
      content. There is a high prevalence of iodine deficiency in these lactating
      postpartum subjects. Urine iodine as micrograms per gram of creatinine is a good
      predictor of breast milk iodine content. In our study, higher breast milk iodine
      was correlated with a higher neonatal TSH. The impact of breast milk iodine
      content on neonatal TSH levels and neuropsychointellectual development needs
      further study.

PMID- 14588103
TI  - Extramedullary hemopoiesis in a thyroid nodule with extensive bone metaplasia and
      mature bone formation.
AB  - Thyroid nodules may undergo a wide range of degenerative change such as
      infarction, hemorrhage, or fibrosis, which may be localized or extensive and
      associated with calcification or even ossification. However, the detection of
      true bone formation in a thyroid nodule is a very rare occurrence. Extramedullary
      hemopoiesis (EMH) has been described in almost every organ of the body, mainly in
      tissues active in hemopoiesis in embryonic life. It is extremely rare for EMH to
      occur in the thyroid gland especially in patients without known chronic anemia.
      We describe a case of a cold thyroid nodule with histologically proven extensive
      bone metaplasia and formation of mature bone with foci of hemopoietic tissue in a
      young woman without chronic anemia, which, to the best of our knowledge, is the
      first to be reported in the English language literature.

PMID- 14588104
TI  - Acute increase in goiter size during a normal pregnancy: an exceptional case
      report.
AB  - This case report illustrates an exceptional clinical situation in which a
      pregnant woman abruptly presented, at 5 months' gestation, with major swelling of
      the thyroid gland that led to respiratory symptoms and emergency hospitalization.
      The medical condition was shown to be caused by acute intrathyroidal hemorrhage
      within a preexisting-albeit until then unnoticed-multinodular goiter. The cause
      of the intrathyroidal hemorrhage could not be firmly delineated, although it
      remains possible that an unusual extraneous cause constituted a "trauma" that
      triggered this rare medical condition.

PMID- 14588105
TI  - Ultrasound-guided interstitial laser photocoagulation of an autonomous thyroid
      nodule: the introduction of a novel alternative.
AB  - Radioiodine ((131)I) and surgery are the standard therapeutic options for the
      solitary autonomous thyroid nodule (AFTN). Percutaneous ethanol injection (PEI)
      has proven to be an effective technique and possible alternative to the
      conventional treatment options. However, PEI is not devoid of side effects and
      often necessitates multiple treatment sessions. We present a case of a 17-year
      old female successfully treated with ultrasound (US)-guided percutaneous
      interstitial laser photocoagulation (ILP) for an AFTN. Initially, she had a serum
      thyrotropin (TSH) of 0.01 mU/L and normal peripheral thyroid hormone levels.
      Scintigraphically it was a hot nodule with suppression of extranodular uptake,
      and ultrasonographically it was a solitary solid 8.2-mL nodule. One treatment
      session (3 W for 650 seconds [1950 J]) normalized serum thyrotropin (TSH) level
      within 2 months and decreased the nodule volume to 4.9 mL (40% reduction) without
      further alterations during an additional 9 months of follow-up. Side effects were
      transient thyrotoxicosis and local pain as seen with PEI. To our knowledge, this
      is the first reported case of ILP used in a patient with a pretoxic thyroid
      nodule. US-guided thermic tissue coagulation with ILP could become a useful
      alternative for the AFTN in patients who cannot or will not undergo surgery or
      treatment with (131)I.

PMID- 14588106
TI  - A case of skull metastasis from thyroid papillary carcinoma.

PMID- 14588107
TI  - Carcinoembryonic antigen mRNA in blood: distinguishing follicular thyroid
      carcinoma from adenoma.

PMID- 14588108
TI  - Panoramic ultrasound of the thyroid.

PMID- 14588109
TI  - Gene expression profile changes are commonly modulated across models and species
      after traumatic brain injury.
AB  - Brain trauma is a major cause of morbidity and mortality, both in adult and
      pediatric populations. Much of the functional deficit derives from delayed cell
      death resulting from induction of neurotoxic factors that overwhelm endogenous
      neuroprotective responses. To identify the potential molecular mechanisms
      underlying such delayed responses, we compared gene expression patterns using
      high-density oligonucleotide arrays at 4, 8, 24, and 72 h after moderate levels
      of lateral fluid percussion-induced brain injury in rats and lateral controlled
      cortical impact injury in mice (a total of 47 profiles). Expression of 82 genes
      in 12 functional categories was significantly changed in both species after
      trauma. The largest number of gene expression changes were found in the
      functional groups related to inflammation (17%), transcription regulation (16%),
      and cell adhesion/extracellular matrix (15%). Fifty percent of genes similarly
      altered across models had not been previously implicated in traumatic brain
      injury. Of particular interest were expression changes in genes linked to
      neurodegeneration, such as ATF3 and lysosomal membrane glycoprotein 2, and to
      neuroprotection including lipocortin 1, calponin 3, gelsolin, Id-1, and p45 NF
      E2. Gene expression profiling across species and models may help identify
      candidate molecular pathways induced by brain injury, some of which may provide
      novel targets for therapeutic intervention.

PMID- 14588111
TI  - Alterations in cerebrospinal fluid apolipoprotein E and amyloid beta-protein
      after traumatic brain injury.
AB  - There is evidence that apolipoprotein E (apoE) and amyloid beta-protein (Abeta),
      which are implicated in the pathology of chronic neurodegenerative disorders, are
      involved in the response of the brain to acute injury; however, human in vivo
      evidence is sparse. We conducted a prospective observational study to determine
      the magnitude and time-course of alterations in cerebrospinal fluid (CSF) apoE
      and Abeta concentrations after traumatic brain injury (TBI), and the relationship
      of these changes to severity of injury and clinical outcome. Enzyme linked
      immunosorbant assay (ELISA) was used to assay apoE, Abeta(1-40) and Abeta(1-42)
      in serial CSF samples from 13 patients with TBI and 13 controls. CSF S100B and
      tau were assayed as surrogate markers of brain injury. There was a significant
      decrease in CSF apoE (p < 0.001) and Abeta (p< 0.001) after TBI contrasting the
      observed elevation in CSF S100B (p < 0.001) and tau (p < 0.001) concentration.
      There was significant correlation (r = 0.67, p = 0.01) between injury severity
      and the decrease in Abeta(1-40) concentration after TBI. In vivo, changes in apoE
      and Abeta concentration occur after TBI and may be important in the response of
      the human brain to injury.

PMID- 14588110
TI  - Neuronal and glial cell number in the hippocampus after experimental traumatic
      brain injury: analysis by stereological estimation.
AB  - Fluid percussion (FP) brain injury causes spatial memory dysfunction in rats
      regardless of injury location (midline vs. lateral). Standard histological
      analysis of the injured brains shows hippocampal neuronal loss after lateral, but
      not midline FP injury. We have used the optical volume fractionator (OVF)
      stereological procedure to quantify neuronal loss and glial proliferation within
      specific subregions of the hippocampus after midline or lateral FP injury. The
      OVF method is a design-based cell counting procedure, which combines cellular
      numerical density estimates (from the optical disector) with volume estimates
      (generated by point counting and the fractionator stereology method) to produce
      an estimate of the absolute cell number. Fifteen adult male Sprague-Dawley rats
      were randomly divided into 3 groups (n = 5/group): midline injury, lateral injury
      and naive. A single fluid percussion pulse was delivered to anesthetized rats in
      the injured groups. At 14 days post-injury, strict morphological criteria enabled
      the estimation of neurons, astrocytes, oligodendrocytes, and microglia in defined
      hippocampal subregions. The results confirm that hippocampal neurons are
      selectively vulnerable to brain injury, particularly observed as a significant
      loss in the hilus following both types of injury and in area CA3 after lateral
      injury. In contrast, the number of astrocytes and oligodendrocytes remains
      unaffected by brain injury, regardless of subregion. However, the significant
      increase in microglia number (bilaterally after midline and ipsilateral following
      lateral injury) suggests that underlying cellular processes continue weeks
      following injury. The implications of the observed cell population changes are
      discussed in relation to the reported cognitive deficits associated with both
      lateral and midline FP brain injury.

PMID- 14588113
TI  - Impact mechanics and axonal injury in a sheep model.
AB  - This paper describes a biomechanical study of axonal injury due to a blunt impact
      to the head. The aim of the experimental model was to produce axonal injury
      analogous to that seen in human trauma while measuring the dynamics of the impact
      and the subsequent kinematics of the head. These measurements were made in a way
      to facilitate the simulation of these experiments using the finite element
      method. Sheep were anaesthetised and ventilated, and subjected to a single impact
      to the lateral aspect of their skull. The impact force was measured throughout
      the duration of the impact and the kinematics of the head was measured using a
      novel implementation of a nine-accelerometer array. The axonal injury was
      identified using amyloid precursor protein (APP) as a marker, intensified using
      antigen retrieval techniques. Axonal injury was consistently produced in all
      animals. Commonly injured regions included the sub-cortical and deep white
      matter, and the periventricular white matter surrounding the lateral ventricles.
      The observed axonal injury was mapped and quantified on three coronal sections of
      each brain. The measure used to describe the injury severity correlated with the
      peak magnitude of the impact force and with peak values of kinematic parameters,
      particularly the peak change of linear and angular velocity.

PMID- 14588112
TI  - Plasma levels of procalcitonin and neopterin in multiple trauma patients with or
      without brain injury.
AB  - Clinical and experimental evidence suggests that traumatic brain injury (TBI)
      leads to a systemic immune response. To examine whether TBI causes a release of
      procalcitonin (PCT) or neopterin (NT) into the circulation, we compared plasmatic
      mediator levels among multiple injured patients with or without TBI. In total, 98
      trauma patients (24 with TBI only, 39 with extracranial injuries excluding TBI,
      and 35 with combined injuries) and 35 healthy volunteers were studied. Blood was
      sampled at 15 predefined time points within 132 h after injury and analysed for
      NT and PCT. Multivariate statistical comparisons were adjusted for different
      severity of head, thorax, abdomen and extremity injuries, as quantified by the
      Abbreviated Injury Scale (AIS). PCT was normal 3 h after trauma, but 24 h after
      extracranial injuries a massive release (median 3 ng/mL) was observed.
      Significant positive associations between injury severity and posttraumatic PCT
      levels were found for abdominal and extremity, but not for cranial or thoracic
      injuries. Only modest changes of marginal statistical significance were detected
      for NT. The maximum increase per AIS point was 9% (95% confidence intervals [CI]:
      3-16%). The effect of TBI on NT release was significant only at 108 h posttrauma
      with a 5% (95% CI: 1-10%) increase per AIS point. TBI induces a release of PCT
      and NT into the plasma, but this effect seems to be smaller for intra- than for
      extracranial injuries, probably due to more extensive surgery for abdominal and
      extremity injuries.

PMID- 14588115
TI  - Effects of daily versus weekly testing and pre-training on the assessment of
      neurologic impairment following diffuse traumatic brain injury in rats.
AB  - A number of test paradigms have been used to determine acute and chronic motor
      and cognitive deficits after experimental traumatic brain injury (TBI). Some
      involve daily testing of either trained or untrained animals whereas others
      utilize periodic testing over extended time periods. Which test paradigm is the
      most appropriate for the assessment of motor and cognitive deficits is, however,
      unclear. In the current study, we have used both daily and weekly testing in
      trained and untrained animals to ascertain which assessment protocol is most
      suited for the detection of functional deficits after diffuse TBI in rats.
      Animals were subjected to severe injury using the impact-acceleration model of
      diffuse TBI. An equal number of animals were also prepared surgically but not
      subject to injury (shams). The rotarod device and the Barnes Maze were used for
      motor and cognitive assessment respectively, with half of the animals being pre
      trained on each test for 10 days prior to injury. The open field test was used to
      assess spontaneous exploratory activity (stress). Following injury, animals were
      assessed for neurologic deficits either on a daily basis (for 10 days) or a
      weekly basis (for 4 weeks). In trained animals, the greatest differences in
      neurologic outcome between injured and sham animals were observed early after
      injury. In contrast, in untrained animals, greatest differences between injured
      and sham animals were observed at later time points. Pre-injury training did not
      improve the rate of cognitive recover, or the rate of motor recovery in the
      weekly test paradigm, but did improve the rate of motor recovery in the daily
      assessment paradigm. Daily assessment promoted rapid functional recovery whereas
      weekly assessments did not significantly affect outcome in injured animals over
      the 4-week assessment period. Spontaneous exploratory activity was decreased
      after TBI and was not influenced by task exposure. These studies demonstrate that
      the functional assessment paradigm needs to be considered when quantifying
      functional deficits following diffuse TBI in rats.

PMID- 14588114
TI  - Transient loss of microtubule-associated protein 2 immunoreactivity after
      moderate brain injury in mice.
AB  - Microtubule-associated protein 2 (MAP2) is important for microtubule stability
      and neural plasticity and appears to be among the most vulnerable of the
      cytoskeletal proteins under conditions of neuronal injury. To evaluate the acute
      effects of moderate severity traumatic brain injury on MAP2, anesthetized, adult
      male C57BL/6 mice were subjected to controlled cortical impact brain injury. At 5
      min, 15 min, 90 min, 4 h, and 24 h following brain injury (n = 4 injured and n =
      1 sham-injured per time point), mice were sacrificed and immunohistochemistry was
      performed on coronal brain sections. Profound decreases in MAP2 immunolabeling
      were observed in the ipsilateral cortex and hippocampal dentate hilus at 5 min
      postinjury and in the ipsilateral hippocampal CA3 area by 4 h postinjury.
      Decreases in MAP2 labeling occurred prior to notable neuronal cell loss.
      Interestingly, cortical MAP2 immunoreactivity returned by 90 min postinjury, but
      the recovery was short-lived within the core in comparison to the periphery of
      the impact site. Partial restoration of MAP2 immunoreactivity was also observed
      in the ipsilateral CA3 and dentate hilus by 24 h postinjury. Our data corroborate
      that MAP2 is an early and sensitive marker for neuronal damage following
      traumatic brain injury. Acute MAP2 loss, however, may not necessarily presage
      neuronal death, even following moderate severity traumatic brain injury. Rather,
      to the best of our knowledge, our data are the first to suggest an intrinsic
      ability of the traumatized brain for MAP2 recovery after injury of moderate
      severity.

PMID- 14588116
TI  - The role of endothelial nitric oxide synthase in the cerebral hemodynamics after
      controlled cortical impact injury in mice.
AB  - Traumatic brain injury causes a reduction in cerebral blood flow, which may cause
      additional damage to the brain. The purpose of this study was to examine the role
      of nitric oxide produced by endothelial nitric oxide synthase (eNOS) in these
      vascular effects of trauma. To accomplish this, cerebral hemodynamics were
      monitored in mice deficient in eNOS and wild-type control mice that underwent
      lateral controlled cortical impact injury followed by administration of either L
      arginine, 300 mg/kg, or saline at 5 min after the impact injury. The eNOS
      deficient mice had a greater reduction in laser Doppler flow (LDF) in the
      contused brain tissue at the impact site after injury, despite maintaining a
      higher blood pressure. L-Arginine administration increased LDF post-injury only
      in the wild-type mice. L-Arginine administration also resulted in a reduction in
      contusion volume, from 2.4 +/- 1.5 to 1.1 +/- 1.2 mm(3) in wild-type mice.
      Contusion volume in the eNOS deficient mice was not significantly altered by L
      arginine administration. These differences in cerebral hemodynamics between the
      eNOS-deficient and the wild-type mice suggest an important role for nitric oxide
      produced by eNOS in the preservation of cerebral blood flow in contused brain
      following traumatic injury, and in the improvement in cerebral blood flow with L
      arginine administration.

PMID- 14588117
TI  - Spinal cord injury induces lesional expression of the proinflammatory and
      antiangiogenic cytokine EMAP II.
AB  - Inflammatory cellular responses to spinal cord injury are promoted by
      proinflammatory messengers. We have analyzed expression of endothelial monocyte
      activating polypeptide II (EMAP II), a proinflammatory, antiangiogenic cytokine
      in rats after spinal cord injury (SCI) in comparison to normal rat spinal cords.
      Immunohistochemical analysis demonstrated a highly significant (p < 0.0001)
      accumulation of EMAP II(+) microglia/macrophages at the lesion site compared to
      remote areas and uninjured controls. After peaking at day 3, EMAP II(+)
      microglia/macrophage cell numbers declined gradually until day 28 after SCI-but
      still remained elevated. Further, EMAP II(+) cells formed clusters in
      perivascular Virchow-Robin spaces reaching a maximum at day 3. Prolonged
      accumulation of EMAP II(+), ED1(+) microglia/macrophages suggest a role of EMAP
      II in the pathophysiology of secondary injury following SCI.

PMID- 14588119
TI  - Locomotor recovery after spinal cord contusion injury in rats is improved by
      spontaneous exercise.
AB  - We have recently shown that enriched environment (EE) housing significantly
      enhances locomotor recovery following spinal cord contusion injury (SCI) in rats.
      As the type and intensity of locomotor training with EE housing are rather poorly
      characterized, we decided to compare the effectiveness of EE housing with that of
      voluntary wheel running, the latter of which is both well characterized and
      easily quantified. Female Wistar rats were made familiar with three types of
      housing conditions, social housing (nine together) in an EE (EHC), individual
      housing in a running wheel cage (RUN, n = 8), and standard housing two together
      (CON, n = 10). Subsequently, a 12.5 gcm SCI at Th8 was produced and animals were
      randomly divided over the three housing conditions. Locomotor function was
      measured regularly, once a week by means of the BBB score, BBB sub score, TLH
      test, Gridwalk test, and CatWalk test. In the RUN group, daily distance covered
      was also measured. Locomotor recovery in the EHC and the RUN groups was equal and
      significantly better than in the CON group. The extent of recovery at 8 weeks
      post injury in the RUN group did not correlate with distance covered. We conclude
      that locomotor training needs to exceed a given threshold in order to be
      effective in enhancing locomotor recovery in this experimental model, but that
      once this threshold is exceeded no further improvement occurs, and that the
      specificity of locomotor training plays little role.

PMID- 14588118
TI  - Minocycline reduces cell death and improves functional recovery after traumatic
      spinal cord injury in the rat.
AB  - We examined the effects of minocycline, an anti-inflammatory drug, on functional
      recovery following spinal cord injury (SCI). Rats received a mild, weight-drop
      contusion injury to the spinal cord and were treated with the vehicle or
      minocycline at a dose of 90 mg/kg immediately after SCI and then twice at a dose
      of 45 mg/kg every 12 h. Injecting minocycline after SCI improved hind limb motor
      function as determined by the Basso-Beattie-Bresnahan (BBB) locomotor open field
      behavioral rating test. Twenty four to 38 days after SCI, BBB scores were
      significantly higher in minocycline-treated rats as compared with those in
      vehicle-treated rats. Morphological analysis showed that lesion size increased
      progressively in both vehicle-treated and minocycline-treated spinal cords.
      However, in response to treatment with minocycline, the lesion size was
      significantly reduced at 21-38 days after SCI when compared to the vehicle
      control. Minocycline treatment significantly reduced the number of terminal
      deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate-biotin nick
      end labeling (TUNEL)-positive cells 24 h after SCI as compared to that of the
      vehicle control. DNA gel electrophoresis also revealed a marked decrease in DNA
      laddering in response to treatment with minocycline. In addition, minocycline
      treatment significantly reduced the specific caspase-3 activity after SCI as
      compared to that of vehicle control. Furthermore, RT-PCR analyses revealed that
      minocycline treatment increased expression of interleukin-10 mRNA but decreased
      tumor necrosis factor-alpha expression. These data suggest that, after SCI,
      minocycline treatment modulated expression of cytokines, attenuated cell death
      and the size of lesions, and improved functional recovery in the injured rat.
      This approach may provide a therapeutic intervention enabling us to reduce cell
      death and improve functional recovery after SCI.

PMID- 14588120
TI  - Mechanical stretch to neurons results in a strain rate and magnitude-dependent
      increase in plasma membrane permeability.
AB  - The mechanism by which mechanical impact to brain tissue is transduced to
      neuronal impairment remains poorly understood. Using an in vitro model of
      neuronal stretch, we found that mechanical stretch of neurons resulted in a
      transient plasma membrane permeability increase. Primary cortical neurons, seeded
      on silicone substrates, were subjected to a defined rate and magnitude strain
      pulse by stretching the substrates over a fixed cylindrical form. To identify
      plasma membrane defects, various sized fluorescent molecules were added to the
      bathing media either immediately before injury or 1, 2, 5, or 10 min after injury
      and removed one minute later. The percent of cells that took up dye depended on
      the applied strain rate, strain magnitude and molecular size. Severe stretch (10
      sec(-1), 0.30) resulted in significant uptake of all tested molecules (ranging
      between 0.5 and 8.9 nm radii) with up to 60% of cells positively stained.
      Furthermore, the neurons remained permeable to the smallest molecule
      (carboxyfluorescein, 380 Da) up to 5 min after severe stretch but were only
      permeable to larger molecules (>/=10 kDa) immediately after stretch. These
      transiently formed membrane defects may be the initiating mechanism that
      translates mechanical stretch to cellular dysfunction.

PMID- 14588123
TI  - Toward optimal health: the experts discuss the metabolic syndrome. Interview by
      Jodi Godfrey Meisler.

PMID- 14588124
TI  - Low-dose estrogen therapy for menopausal women: a review of efficacy and safety.
AB  - BACKGROUND: Recent adverse events involving research of traditional estrogen
      therapy have led to interest in lower-than-standard doses of menopausal estrogen
      therapy. METHOD: The Medline (1966-present) database was searched for randomized
      controlled trials (keywords: low-dose estrogen, minimum dose AND estrogen,
      menopause, and osteoporosis) regarding hot flashes, endometrial hyperplasia,
      vaginal bleeding, breast tenderness, and bone density. Studies are only a few
      years in duration. RESULTS: The decrease in hot flashes with half-strength
      estrogens, range 60%-70%, is less than the 80%-90% reduction with standard
      dosing. Some low-dose preparations preserve lumbar and femoral bone density
      (although the degree of effect and quality of evidence vary among preparations).
      Bone density effects are dose dependent for conjugated equine estrogen (CEE),
      transdermal estradiol ethinyl (E(2)), norethindrone acetate (E(2)/NETA), oral
      E(2), and esterified estrogens. Bone preservation is likely to be less
      efficacious with low-dose estrogens than with traditional doses. Low-dose
      estrogen alone may not protect bone unless adequate calcium is given. Breast
      tenderness and skeletal effects are likely dose dependent. The longest
      endometrial safety data are 2-year data, reported for 5 microg/1 mg EE(2)/NETA
      and for 0.3 mg/day esterified estrogens. Some low-dose preparations have better
      vaginal bleeding profiles than do higher dose preparations. Breast tenderness is
      not totally averted with new lower-dose preparations. There are no fracture,
      breast cancer, or cardiovascular outcome data and a general lack of direct head
      to-head comparisons involving low-dose preparations. CONCLUSIONS: Serious adverse
      effects linked with traditional doses of estrogens may not be averted with lower
      dose preparations, and low-dose preparations should not yet be emphasized as
      being safer than traditional (e.g., 0.625 mg/day CEE doses).

PMID- 14588125
TI  - Lipid-lowering drug use and breast cancer in older women: a prospective study.
AB  - OBJECTIVE: To test the hypothesis that use of lipid-lowering drugs reduces the
      risk of breast cancer in older women. METHODS: This was a multicenter prospective
      cohort study conducted at four community-based clinical centers in the United
      States, including 7528 Caucasian women, mean age 77 years. The main outcome
      measure was incident breast cancer confirmed by medical record and pathology
      reports identified over an average of 6.8 years (244 cases). RESULTS: The use of
      lipid-lowering drugs was reported by 576 women (7.7%). The age-adjusted incidence
      of breast cancer was 3.1/1000 person-years among statin users, 1.4 among women
      using other lipid-lowering agents, and 5.0 among nonusers. After adjustment for
      age and body weight, the relative risk (RR) of breast cancer among statin users
      was 0.28 (95% confidence intervals [CI] 0.09-0.86), and among women who used
      other lipid-lowering drugs, it was 0.37 (95% CI 0.14-0.99) in comparison to
      nonusers. The combined group of lipid-lowering drug users had a 68% reduction in
      the risk of breast cancer (95% CI 32%-85%). Further adjustment for hormone use,
      family history of breast cancer, mammography use, or other risk factors did not
      alter the results. CONCLUSIONS: Older women who use lipid-lowering drugs may have
      a reduced risk of breast cancer. Given the widespread use of statins in older
      women, these results could have a large public health impact. However, these
      findings need confirmation in other prospective studies, as they were based on a
      small number of breast cancer events.

PMID- 14588126
TI  - Thoughts on individualizing hormone replacement therapy based on the
      postmenopausal health disparities study data.
AB  - BACKGROUND: This study presents an approach that can be used to address the
      controversy about the long-term risks and benefits of hormone replacement therapy
      (HRT). METHODS: Categories of estradiol (E(2)) levels based on the mean and
      standard deviation (SD) in postmenopausal women not treated with HRT were
      created. E(2) levels achieved in women treated with oral or patch replacement
      therapy were examined. In the application of this method, data from the
      Postmenopausal Health Disparities Study were used because identical E(2) assay
      methods were used for all postmenopausal women in the study population. RESULTS:
      The findings demonstrated that approximately 42% of HRT-treated women had E(2)
      levels less than the mean E(2) level plus 1 SD in the controls (37 pg/ml). In
      contrast, approximately 11% had E(2) levels greater than the mean E(2) level plus
      6 SD in the controls (126 pg/ml). Menopausal vasomotor and vaginal symptoms
      decreased ( p < 0.06) in increasing control-based E(2) categories. Levels of both
      follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were
      significantly correlated with the E(2) control-based categories (both p = 0.000).
      When hormone variables and other variables (e.g., moderate alcoholic beverage
      consumption and bilateral ovariectomy) known to be determinants of E(2) levels in
      postmenopausal women not treated with HRT were included in the model for oral or
      patch HRT-treated women, 51.1% of the variability in the control-based E(2)
      categories was explained when menopause duration, use of oral as opposed to patch
      therapy, body mass index (BMI), scores for medical compliance, and being white
      entered the equation as statistically significant predictors. CONCLUSIONS: First,
      there is substantial variability in E(2) concentrations achieved with
      conventional oral and patch HRT. Second, various factors that are statistically
      significant predictors of response categories have been identified. Third,
      race/ethnic group plays a role in the response to HRT. Finally, the demonstration
      of variable responses to HRT and the application of the categorization paradigm
      presented will be useful in resolving the controversy about the risks and
      benefits of conventional HRT.

PMID- 14588127
TI  - Attitudes to prophylactic surgery and chemoprevention in Australian women at
      increased risk for breast cancer.
AB  - BACKGROUND: Because of the uncertain efficacy of breast cancer screening in women
      at increased risk of developing breast cancer, bilateral prophylactic
      oophorectomy and mastectomy are considered management options for high-risk
      women. Data on the attitudes to prophylactic strategies of high-risk women who
      have not attended specialist clinics are needed to ascertain the need for patient
      education and provide the basis for planning of support services. METHODS: Three
      hundred seventy-one women unaffected by cancer and with unknown mutation status
      from families with a dominantly inherited susceptibility to breast cancer,
      recruited through a large Australian population-based, epidemiological study,
      were assessed using a mailed self-administered questionnaire with validated
      measures of psychological outcome. RESULTS: Sixteen percent of women reported
      considering prophylactic mastectomy, and 1% had already had the procedure. Among
      women with a family history of breast/ovarian cancer, 33% had considered and 5%
      had already had a prophylactic oophorectomy. Twenty-three percent of women
      reported considering taking tamoxifen if it were shown to prevent breast cancer.
      Consideration of prophylactic oophorectomy (OR = 1.51 for a 10% change in
      perceived risk, 95% CI 1.14-1.99, p = 0.0045) and tamoxifen (OR = 1.14 for a 10%
      change in perceived risk, 95% CI 1.002-1.30, p = 0.047) were positively
      associated with perceived cancer risk. CONCLUSIONS: Attitudes to prophylactic
      surgery and psychological distress levels in high-risk women participating in an
      epidemiological study appear to be comparable to those of women attending
      familial cancer clinics and indicate that women attending high-risk clinics may
      be representative of the larger population of women at increased risk.

PMID- 14588128
TI  - The impact of a family history of breast cancer on screening practices and
      attitudes in low-income, rural, African American women.
AB  - BACKGROUND: Women with a family history of breast cancer are at increased risk
      for developing cancer and, therefore, might be expected to engage in early
      detection practices more actively than women without a family history.
      Alternatively, women with a family history may avoid thinking about cancer and
      have attitudes and practices that do not promote early detection. METHODS: This
      study examined breast cancer attitudes and practices among African American women
      aged >or=50 who had not had a mammogram in the last 2 years. RESULTS: Phone
      survey data from 320 female clients of low-income, rural primary care clinics
      (91% African American) indicated that 15% self-reported a family history of
      breast cancer (FH(+)). Half of the FH(+) women did not know their relative risk
      of developing breast cancer. Of those providing a risk estimate, 67% perceived
      themselves at low risk compared with other women their age. Perceived relative
      risk was comparable between FH(+) and FH(-) women. Further, FH(+) women did not
      indicate greater worry about breast cancer, nor did they have more accurate
      knowledge of mammography recommendations than FH(-) women. Two thirds of FH(+)
      women had never had a mammogram. Monthly breast self-examination did not differ
      between FH(+) and FH(-) women. CONCLUSIONS: Thus, neither knowledge of a positive
      family history nor perceived relative risk of breast cancer was associated with
      either increased or decreased early detection practices among these low-income,
      rural, African American women who have underused mammography. Furthermore, a
      substantial proportion of FH(+) women had not ever participated in screening
      mammography. Interventions to increase mammography rates in this population of
      underusers are indicated.

PMID- 14588129
TI  - The safety net: a cost-effective approach to improving breast and cervical cancer
      screening.
AB  - PURPOSE: The purposes of the study were (1). to assess the cost-effectiveness of
      three interventions to deliver breast and cervical cancer screening to women
      unscreened for >or=3 years and (2). to determine the relation of an invasive
      cervical cancer diagnosis to the interval since the last true screening test.
      METHODS: In a randomized trial, women were randomly assigned to (1). usual care,
      (2). letter plus follow-up letter, (3). letter plus follow-up phone call, (4).
      phone call plus follow-up phone call. Screening within 12 weeks was the outcome.
      A 5-year retrospective review of cervical cancer cases and screening histories
      was done. RESULTS: The 8% of women not screened for >or=5 years had 62% of the
      invasive cervical cancer cases. Mammography outreach led to screening in 10%,
      24%, 51%, and 50% of controls, letter/letter, letter/phone, and phone/phone
      interventions groups, respectively. Cervical cancer screening outreach led to
      screening in 17%, 22%, 54%, and 50% of the respective groups. Letter reminders
      alone produced fewer tests at substantially higher costs than did personalized
      telephone notification. CONCLUSIONS: For cervical cancer, only 1 person in 12 was
      not screened in the preceding 5 years, but these accounted for nearly two thirds
      of invasive cancers. Aggressive outreach to the rarely screened is an important
      part of screening programs. Letter reminder, followed by a telephone appointment
      call, was the most cost-effective approach to screening rarely screened women.
      Lack of accurate information on prior hysterectomy adds substantial unnecessary
      costs to a screening reminder program.

PMID- 14588130
TI  - Aging may be associated with concentrations of tamoxifen and its metabolites in
      breast cancer patients.
AB  - BACKGROUND: Although tamoxifen (TAM) is the predominant adjuvant therapy for
      estrogen receptor positive (ER(+)) breast tumors, 50% of breast cancer patients
      do not respond positively to this therapy, or they experience adverse side
      effects. This variability in TAM responsiveness may be due to differences in TAM
      metabolism that stem from differences in race, age, and body mass index (BMI).
      Thus, the purpose of this study was to test the hypothesis that race, age, and
      BMI are associated with the metabolism of TAM to two primary metabolites, N
      desmethyltamoxifen (N-DMT) and 4-hydroxytamoxifen (4-OHT). METHODS: The study
      design was cross-sectional, and data were analyzed using independent sample t
      tests and multiple linear regression models. Breast cancer patients (n = 99)
      taking TAM for at least 30 days were recruited from a local hospital clinic. Each
      participant provided informed consent, completed a questionnaire, and donated a
      blood sample. The questionnaire was used to ascertain race, age, and BMI. The
      blood samples were used to measure plasma concentrations of TAM, N-DMT, and 4
      OHT. RESULTS: Plasma concentrations of TAM, N-DMT, and 4-OHT differed among
      individual patients. Age, but not race and BMI, was positively associated with
      plasma concentrations of TAM and N-DMT, even after adjustment for potential
      confounders (p = 0.02 for TAM and p = 0.03 for N-DMT). CONCLUSIONS: This study
      suggests that aging may alter the metabolism of TAM. As increased levels of TAM
      and TAM metabolites may provide a possible explanation for why older women taking
      TAM are at increased risk for adverse side effects, future studies should
      determine whether age-related differences in the concentrations of TAM and TAM
      metabolites are associated with differences in TAM toxicity or responsiveness.

PMID- 14588132
TI  - A randomized trial of incentives to improve response rates to a mailed women's
      health questionnaire.
AB  - BACKGROUND: Mailed questionnaires can be a convenient method for collecting data
      on women's health, although poor response rates are a concern. METHODS: As part
      of a survey of women's health conducted in Maryland in 2001, a randomized trial
      was performed to assess the effects of two incentives (US dollars 1.00 or a
      lottery ticket) as well as precontact with an introductory postcard on response
      rates. Questionnaires were mailed to 3000 women aged 40-60 who were randomized to
      one of six incentive/precontact groups: lottery/postcard, money/postcard,
      postcard only, lottery only, money only, or no incentive/no postcard. RESULTS:
      The overall response rate was 37.6%. Each incentive/precontact group yielded a
      higher response rate than the no incentive/no postcard group, although only the
      response rates for the lottery/postcard group (41.3%) and the money only group
      (40.0%) were significantly higher than that of the no incentive/no postcard group
      (33.1%). Money was the only factor that had a significant independent effect on
      likelihood of response (hazards ratio [HR] compared to no incentive = 1.22, 95%
      confidence interval [CI] = 1.03, 1.43). Response rates were lower in minority ZIP
      codes, although the effects of the incentives were generally greater than in the
      nonminority ZIP codes. CONCLUSIONS: These results indicate that response rates to
      mailed women's health questionnaires may be improved with modest incentives,
      particularly cash incentives.

PMID- 14588131
TI  - Posttraumatic stress in women after the September 11 terrorist attacks in New
      York City.
AB  - BACKGROUND: Women have been shown to be at higher risk than men of developing
      posttraumatic stress disorder (PTSD) after traumatic events. Women in New York
      City were more likely than men to have probable PTSD 5-8 weeks after the
      September 11, 2001, terrorist attacks on the World Trade Center. We explored the
      factors that could explain the higher prevalence of probable PTSD among women in
      the aftermath of the attacks. METHODS: Data from a telephone survey of a randomly
      selected group of residents of Manhattan living south of 110th street, conducted
      5-8 weeks after September 11, were used in these analyses. The survey assessed
      demographic information, lifetime experience of traumatic events, life stressors,
      social support, event exposure variables, perievent panic attacks, postevent
      concerns, and probable PTSD related to the attacks. We determined the
      contribution of key covariates that could explain the gender-probable PTSD
      relation through stratified analyses and manual stepwise logistic regression
      model building. RESULTS: Among 988 respondents, women were two times more likely
      than men to report symptoms consistent with probable PTSD after the September 11
      attacks. When adjusted for potential confounders, the association between gender
      and probable PTSD diminished from OR = 2.2 (95% confidence interval [CI] 1.3-3.6)
      to OR = 1.2 (95% CI 0.7-2.2). CONCLUSIONS: These results suggest that specific
      behavioral and biographic factors (including previous traumatic experiences and
      psychological disorders, social responsibilities, and perievent emotional
      reactions) explained most of the excess burden of probable PTSD among women after
      a disaster. Isolating the characteristics that place women at greater risk for
      probable PTSD after disasters can inform public health prevention strategies and
      spur further research.

PMID- 14588134
TI  - Human cells from cloned embryos in research and therapy.

PMID- 14588135
TI  - Epigenetic reprogramming of cloned animals.

PMID- 14588136
TI  - Effect of timing of the removal of oocyte chromosomes before or after injection
      of somatic nucleus on development of NT embryos.
AB  - Cloning methods are now well described and becoming routine. Yet the frequency at
      which live cloned offspring are produced (as a percentage of starting one-cell
      embryos) remains below 5% irrespective of nucleus donor species or cell type. In
      considering the cause(s) of this universally low efficiency, features common to
      all cloning protocols are strong candidates. One such shared feature is
      enucleation; the donor nucleus is inserted into an enucleated cytoplast
      (ooplast). However, it is not known whether a nucleus-free metaphase II oocyte is
      developmentally impaired other than by virtue of lacking chromosomes, or if in
      nuclear transfer protocols, enucleation removes factors necessary to reprogram
      the incoming nucleus. We have here investigated the role of enucleation in
      nuclear transfer. Three hours after the injection of cumulus cell nuclei into non
      enucleated oocytes, 65% contained two distinct metaphase spindles, with the
      remainder exhibiting a single spindle in which oocyte-derived and nucleus donor
      chromosomes were mixed. However, staining only one hour after donor nucleus
      insertion revealed that most had two discrete spindles. In the absence of
      staining, the donor nucleus spindle was not visible. This provided a
      straightforward way to identify and select the oocyte-derived metaphase
      chromosomes 1 h after donor nucleus microinjection, and 34-41% cloned embryo
      developed to the morulla-blastocyst stage following Sr(2+)-induced activation. Of
      these, two (1% of starting one-cell embryos) developed to term, an efficiency
      which is comparable to that obtained for controls (6 clone; 1-2%) in which
      enucleation preceded nuclear transfer. In conclusion, the timing of the removal
      of oocyte chromosomes before or after injection of somatic nucleus had no effect
      on cloned embryo development. These findings argue that neither oocyte chromosome
      depletion per se, nor the potential removal of "reprogramming" factors during
      enucleation explain the low efficiency of nuclear transfer cloning.

PMID- 14588137
TI  - Production of nuclear transfer llama (lama glama) embryos from in vitro matured
      llama oocytes.
AB  - To date, there have been no reports of somatic cell nuclear transfer in llamas.
      The application of this methodology to the camelid industry could be helpful in
      the propagation of genetically valuable animals. The objective of this study was
      to produce nuclear transfer llama embryos comparing the development of these
      llama embryos cultured in either CR1aa medium (treatment A) or G1.2 medium
      (treatment B) medium. Llamas were superstimulated by double dominant follicle
      reduction 12 days apart, followed by pFSH administered in daily descending doses
      over a 3-day interval (total dose of 200 mg). Animals were ovariectomized by
      flank laparotomy, follicles were aspirated from excised ovaries and oocytes were
      in vitro matured for a 30-h period. Adult female llama fibroblasts were used as
      donor karyoplasts and injected into enucleated llama oocytes. Embryo development
      was assessed after 2 days of culture. A total of 307 follicles were aspirated
      from nine treated females, resulting in 298 (97%) oocytes recovered. Of a total
      of 229 evaluated oocytes, 120 (52%) achieved nuclear maturation. Of a total of 80
      reconstructed couplets, 50 (62.5%) were successfully fused. Subsequent cleavage
      rates were 32 and 40% for treatments A and B, respectively, with no significant
      difference (p < 0.05) detected between treatment groups. A total of 11 embryos (8
      cell to morula stages) were transferred to synchronized recipient llamas.
      Ultrasonography at 14 days post-transfer indicated that no pregnancies were
      established. This study shows that nuclear transfer can be successfully applied
      to the production of llama embryos. Further research is needed to identify
      optimal parameters to improve efficiency of nuclear transfer in this species.

PMID- 14588139
TI  - Comparison of milk produced by cows cloned by nuclear transfer with milk from non
      cloned cows.
AB  - Cloning technologies, including embryo splitting and nuclear transfer, were
      introduced into dairy cattle breeding in the early 1980s. With the recent
      worldwide attention on the cloning of sheep ("Dolly") and cows ("Gene"), the
      potential food safety concerns for food products derived from cloned animals
      needs to be addressed. There has been no study of the composition of milk
      produced by cloned cows. In this preliminary study, we evaluated the composition
      of milk from 15 lactating non-embryonic cell cloned cows and six non-cloned
      lactating cows over a single season. The cloned cows came from five unique
      genetic lines and three distinct breeds. Milk samples were analyzed for total
      solids, fat, fatty acid profile, lactose, protein and compared to non-cloned and
      literature values. Gross chemical composition of milk from cloned cows was
      similar to that of the non-cloned cows and literature values. Our results lead us
      to conclude that there are no obvious differences in milk composition produced
      from cloned cows compared to non-cloned cows.

PMID- 14588138
TI  - Growth restricted in vitro culture conditions alter the imprinted gene expression
      patterns of mouse embryonic stem cells.
AB  - Embryonic stem (ES) cell-derived clones and chimeras are often associated with
      growth abnormalities during fetal development, leading to the production of
      over/under-weight offspring that show elevated neonatal mortality and morbidity.
      Due to the role played by imprinted genes in controlling fetal growth, much of
      the blame is pointed at improper epigenetic reprogramming of cells used in the
      procedures. We have analyzed the expression pattern of two growth regulatory
      imprinted genes, namely insulin like growth factor II (Igf2) and H19, in mouse ES
      cells cultured under growth restricted conditions and after in vitro aging.
      Culture of cells with serum-depleted media (starvation) and at high cell density
      (confluence) increased the expression of both imprinted genes and led to aberrant
      methylation profiles of differentially methylated regions in key regulatory sites
      of Igf2 and H19. These findings confirm that growth constrained cultures of ES
      cells are associated with alterations to methylation of the regulatory domains
      and the expression patterns of imprinted genes, suggesting a possible role of
      epigenetic factors in the loss of developmental potential.

PMID- 14588140
TI  - Redox control of growth factor signaling in heart, lung, and circulation.

PMID- 14588141
TI  - Enalapril increases mitochondrial nitric oxide synthase activity in heart and
      liver.
AB  - Heart and liver mitochondria isolated from rats treated with enalapril, 3-30
      mg/kg/day in the drinking water for 7-120 days, showed a time- and dose-dependent
      increased nitric oxide (NO) production in the range of 14-250%. Heart and liver
      mitochondria from control rats produced 0.69 and 0.50 nmol of NO/min/mg of
      protein, respectively, as determined by dual wavelength spectrophotometry (577
      591 nm) following hemoglobin oxidation to methemoglobin. The response to
      enalapril treatment, attributed to a gene-mediated up-regulation of mitochondrial
      nitric oxide synthase (mtNOS) activity, was half-maximal at 5-6 days and was
      maintained up to 120 days. Enalapril-treated animals showed an increased mtNOS
      functional activity in heart mitochondria that inhibited state 3 O(2) uptake
      (from 22% in control rats to 43%) and increased state 4 hydrogen peroxide
      (H(2)O(2)) production (from 30% in control rats to 52%). Calculated heart
      intramitochondrial NO and H(2)O(2) steady-state concentrations were increased 66%
      and 20%, respectively, by enalapril treatment. Signaling pathways dependent on
      mitochondrial NO and H(2)O(2) may account for the beneficial effects of enalapril
      in aging mammals.

PMID- 14588142
TI  - Regulation of glutathione by oxidative stress in bovine pulmonary artery
      endothelial cells.
AB  - Glutathione plays important roles as an intracellular antioxidant and in the
      maintenance of cellular thiol-disulfide balance. In addition, glutathione may
      regulate cell growth signaling induced by oxidative stress. We previously
      reported that cellular glutathione is up-regulated by bleomycin in bovine
      pulmonary artery endothelial cells. The present study examined effects of
      hydrogen peroxide (H(2)O(2)) on cell growth and glutathione levels. Exogenous
      addition of H(2)O(2) induced biphasic effects on cell growth; 1 micro M was
      stimulatory and >10 micro M was inhibitory. However, both growth-promoting and
      inhibitory levels of H(2)O(2) increased cellular glutathione levels. Whereas 1
      micro M H(2)O(2) moderately but significantly increased glutathione, 30 micro M
      caused a more substantial increase. Like bleomycin, both concentrations of
      H(2)O(2) activated DNA binding of antioxidant response element (ARE), a
      regulatory element in the promoter of the gamma-glutamylcysteine synthetase heavy
      chain subunit, a key regulator of glutathione synthesis. However, only high
      concentrations of H(2)O(2) activated p44/42 mitogen-activated protein (MAP)
      kinase. Thus, cellular glutathione is up-regulated by H(2)O(2), perhaps via
      activating ARE-binding factors in a mechanism independent of MAP kinase. H(2)O(2)
      mediated increase in glutathione and activation of ARE binding may play important
      roles in growth and death of pulmonary artery endothelial cells.

PMID- 14588143
TI  - Estrogen modulates xanthine dehydrogenase/xanthine oxidase activity by a receptor
      independent mechanism.
AB  - Hypoxia causes up-regulation and activation of xanthine dehydrogenase/xanthine
      oxidase (XDH/XO) in vitro and in the lungs in vivo. This up-regulation, and the
      likely corresponding production of reactive oxygen species, may underlie the
      pathogenesis of an array of disorders. Thus, compounds that prevent hypoxia
      induced increase in XDH/XO activity may provide a therapeutic strategy in such
      disorders. The antioxidant properties of estrogens have been demonstrated in
      several studies. However, the effect of these compounds on XDH/XO has not been
      explored previously. The aim of this study was to investigate the effects of
      estrogen on hypoxia-induced increase in XDH/XO activity. Rat pulmonary artery
      microvascular endothelial cells were exposed to normoxia or hypoxia in the
      presence or absence of 17beta- or 17alpha-estradiol. The XDH/XO enzyme and gene
      promoter activities were measured in different groups of cells. Hypoxia caused a
      twofold increase in XDH/XO enzymatic and promoter activity. Either of the
      estradiol stereoisomers prevented the hypoxia-induced increase in XDH/XO
      enzymatic activity, but not the promoter activity. ICI 182,780, an antagonist of
      the estrogen receptor, failed to block the inhibitory effect of estradiol on
      XDH/XO. In conclusion, 17alpha- and 17beta-estradiol modulate the hypoxia-induced
      regulation of XDH/XO activity at a posttranscriptional level by a receptor
      independent mechanism.

PMID- 14588144
TI  - Redox regulation of PI3K/Akt and p53 in bovine aortic endothelial cells exposed
      to hydrogen peroxide.
AB  - To clarify the apoptotic and survival signal transduction pathways in activated
      vascular endothelial cells exposed to oxidative stress, the effects of inhibitors
      of signal transduction on hydrogen peroxide (H(2)O(2))-induced apoptosis in
      bovine aortic vascular endothelial cells (BAEC) were examined. Treatment of BAEC
      with 1 mM H(2)O(2) caused increases of DNA fragmentation, p53 expression, Bax/Bcl
      2 ratio, and the activities of caspases 3 and 9. The increases of DNA
      fragmentation, Bax/Bcl-2 ratio, and caspase activities were abrogated by BAPTA-AM
      (an intracellular Ca(2+) chelator) and N-acetyl-L-cysteine (an antioxidant), and
      augmented by wortmannin [a phosphatidylinositol 3-kinase (PI3K) inhibitor]. The
      increase of the intracellular Ca(2+) concentration ([Ca(2+)](i)) observed in
      H(2)O(2)-stimulated cells was unaffected by wortmannin, suggesting that the
      potentiating effect of wortmannin on the apoptosis was not due to an alteration
      of [Ca(2+)](i). H(2)O(2) increased the levels of PI3K activity and Akt
      phosphorylation. Both were attenuated by wortmannin and, to a lesser extent, by
      genistein (a tyrosine kinase inhibitor) and suramin (a growth factor receptor
      inhibitor), but not affected by BAPTA-AM. These results suggest that H(2)O(2)
      induces Ca(2+)-dependent apoptosis and Ca(2+)-independent survival signals such
      as redox-regulated activation of PI3K/Akt, which is partly mediated by the
      activation of growth factor receptors in BAEC.

PMID- 14588145
TI  - Redox regulation of reactive oxygen species-induced p38 MAP kinase activation and
      barrier dysfunction in lung microvascular endothelial cells.
AB  - Reactive oxygen species (ROS)-mediated compromise of endothelial barrier
      integrity has been implicated in a number of pulmonary disorders, including adult
      respiratory distress syndrome, pulmonary edema, and vasculitis. The mechanisms by
      which ROS increase endothelial permeability are unclear. We hypothesized that ROS
      induced changes in cellular redox status (thiols) may contribute to endothelial
      barrier dysfunction. To test this hypothesis, we used N-acetylcysteine (NAC) and
      diamide to modulate intracellular levels of cellular glutathione (GSH) and
      investigated hydrogen peroxide (H(2)O(2))-mediated mitogen-activated protein
      kinase (MAPK) activation and transendothelial electrical resistance (TER).
      Exposure of bovine lung microvascular endothelial cells (BLMVECs) to H(2)O(2), in
      a dose- and time-dependent fashion, increased endothelial permeability.
      Pretreatment of BLMVECs with NAC (5 mM) for 1 h resulted in partial attenuation
      of H(2)O(2)-induced TER (a measure of increase in permeability) and GSH.
      Furthermore, treatment of BLMVECs with diamide, which is known to reduce the
      intracellular GSH, resulted in significant reduction in TER, which was prevented
      by NAC. To understand further the role of MAPKs in ROS-induced barrier
      dysfunction, we examined the role of extracellular signal-regulated kinase (ERK)
      and p38 MAPK on H(2)O(2)- and diamide-mediated permeability changes. Both
      H(2)O(2) and diamide, in a dose-dependent manner, activated ERK and p38 MAPK in
      BLMVECs. However, SB203580, an inhibitor of p38 MAPK, but not PD98059, blocked
      H(2)O(2)- and diamide-induced TER. Also, NAC prevented H(2)O(2)- and diamide
      induced p38 MAPK, but not ERK activation. These results suggest a role for redox
      regulation of p38 MAPK in ROS-dependent endothelial barrier dysfunction.

PMID- 14588146
TI  - Regulation of hypertrophic and apoptotic signaling pathways by reactive oxygen
      species in cardiac myocytes.
AB  - Increasing evidence suggests that oxidative and nitrosative stress play an
      important role in regulation of cardiac myocyte growth and survival. The
      cardiovascular system is continuously exposed to both reactive oxygen species
      (ROS) and nitrogen species (RNS), collectively termed reactive inflammatory
      species (RIS), and imbalances between the enzymes that regulate their
      bioavailability are associated with cardiac hypertrophy and the pathogenesis of
      cardiomyopathies, myocardial infarction and heart failure. It is now clear that
      RIS act as critical regulators of cardiac myocyte hypertrophy and apoptosis
      through control of redox-sensitive signaling cascades, such as tyrosine kinases
      and phosphatases, protein kinase C, and mitogen-activated protein kinases. This
      review will focus on the mechanisms by which ROS/RNS modulate cardiac myocyte
      growth and apoptosis induced by neurohormones and cytokines, and will discuss
      evidence for a role in the pathophysiology of heart failure.

PMID- 14588147
TI  - Growth factor signaling for cardioprotection against oxidative stress-induced
      apoptosis.
AB  - The heart is subjected to oxidative stress during various clinical situations,
      such as ischemia-reperfusion injury and anthracycline chemotherapy. The loss of
      cardiac myocytes is the major problem in heart failure; thus, it is important to
      protect cardiac myocytes against cell death. Various growth factors, including
      insulin like growth factor, hepatocyte growth factor, endothelin-1, fibroblast
      growth factor, and transforming growth factor, have been shown to protect the
      heart against oxidative stress. The mechanism of growth factor-mediated
      cardioprotection may involve the attenuation of cardiac myocyte apoptosis. The
      present article summarizes the current knowledge on the molecular mechanisms of
      growth factor-mediated antiapoptotic signaling in cardiac myocytes. Insulin-like
      growth factor-1 activates phosphatidylinositol 3' -kinase and extracellular
      signal-regulated kinase pathways. Recent data showed that GATA-4 might be an
      important mediator of cardiac myocyte survival by endothelin-1 and hepatocyte
      growth factor. These growth factors, as well as mediators of growth factor
      signaling, may be useful in therapeutic strategies against oxidative stress
      induced cardiac injury.

PMID- 14588148
TI  - The role of endogenous NADPH oxidases in airway and pulmonary vascular smooth
      muscle function.
AB  - Reactive oxygen species generated from NADPH oxidase(s) in airway smooth muscle
      cells and pulmonary artery smooth muscle cells are important signaling
      intermediates. Nox4 appears to be the predominant gp91 homologue in these cells.
      However, expression of NADPH oxidase components is dependent on phenotype, and
      different homologues may be expressed during different functional states of the
      cell. NADPH oxidase(s) appear to be important not only for mitogenesis by these
      cells, but also for O(2) sensing. The regulation of NADPH oxidase(s) in airway
      and pulmonary artery smooth muscle cells has important implications for the
      pathobiochemistry of asthma and pulmonary vascular diseases.

PMID- 14588149
TI  - Role of reactive oxygen species in vascular remodeling associated with pulmonary
      hypertension.
AB  - Several manifestations of neonatal pulmonary hypertension are associated with
      vascular remodeling, resulting in increased muscularity of the small pulmonary
      arteries. Abnormal structural development of the pulmonary vasculature has been
      implicated in persistent pulmonary hypertension of the newborn (PPHN). Increased
      plasma levels of the vasoconstrictor endothelin-1 (ET-1) have been demonstrated
      in patients with PPHN, which is likely to contribute to hypertension. In
      addition, several studies have identified a role for ET-1 in the proliferation of
      vascular smooth muscle cells (SMCs), suggesting that ET-1 may also be involved in
      the vascular remodeling characteristic of this disease. However, the mechanisms
      of ET-1-induced SMC proliferation are unclear and appear to differ between cells
      from different origins within the vasculature. In SMCs isolated from fetal
      pulmonary arterial cells, ET-1 stimulated proliferation via an induction of
      reactive species (ROS). Furthermore, other lines of evidence have demonstrated
      the involvement of ROS in ET-1-stimulated SMC growth, suggesting that ROS may be
      a common factor in the mechanisms involved. This review discusses the potential
      roles for ROS in the abnormal pulmonary vascular development characteristic of
      PPHN, and the treatment strategies arising from our increasing knowledge of the
      molecular mechanisms involved.

PMID- 14588150
TI  - Activation of tyrosine kinases by reactive oxygen species in vascular smooth
      muscle cells: significance and involvement of EGF receptor transactivation by
      angiotensin II.
AB  - Enhanced production of reactive oxygen species (ROS) such as H(2)O(2) and a
      failure in ROS removal by scavenging systems are hallmarks of several
      cardiovascular diseases such as atherosclerosis and hypertension. ROS act as
      second messengers that play a prominent role in intracellular signaling and
      cellular function. In vascular smooth muscle cells (VSMCs), a vascular pathogen,
      angiotensin II, appears to initiate growth-promoting signal transduction through
      ROS-sensitive tyrosine kinases. However, the precise mechanisms by which tyrosine
      kinases are activated by ROS remain unclear. In this review, the current
      knowledge that suggests how certain tyrosine kinases are activated by ROS, along
      with their functional significance in VSMCs, will be discussed. Recent findings
      suggest that transactivation of the epidermal growth factor receptor by ROS
      requires metalloprotease-dependent heparin-binding epidermal growth factor-like
      growth factor production, whereas other ROS-sensitive tyrosine kinases such as
      PYK2, JAK2, and platelet-derived growth factor receptor require activation of
      protein kinase C-delta. Each of these ROS-sensitive kinases could mediate
      specific signaling critical for pathophysiological responses. Detailed analysis
      of the mechanism of cross-talk and the downstream function of these various
      tyrosine kinases will yield new therapeutic interventions for cardiovascular
      disease.

PMID- 14588151
TI  - Oxidants in receptor tyrosine kinase signal transduction pathways.
AB  - The accumulation of oxygen in the atmosphere created an evolutionary stress for
      organisms to survive because oxygen, while the by-product of photosynthesis and
      an important substrate in oxidative metabolism, can also be partially reduced to
      form toxic products. These forms of oxygen, reduced by one electron or two
      electrons, yield superoxide anion (O(2).-) and hydrogen peroxide (H(2)O(2)),
      respectively. Recent studies suggest that reactive oxygen species (ROS) such as
      O(2).- and H(2)O(2) function as mitogenic mediators of activated growth-factor
      receptor signaling. Reported data imply that growth factor-stimulated ROS
      generation can mediate intracellular signaling pathways by activating protein
      tyrosine kinases, inhibiting protein tyrosine phosphatase, and regulating redox
      sensitive gene expression. This review examines the mechanisms of growth factor
      induced generation of ROS and their roles in specific receptor tyrosine kinase
      signaling pathways.

PMID- 14588152
TI  - Oxidative stress-induced signal transduction pathways in cardiac myocytes:
      involvement of ROS in heart diseases.
AB  - Reactive oxygen species (ROS) are proposed to contribute to the deterioration of
      cardiac function in patients with heart diseases. It has been reported that ROS
      are increased in the failing heart and involved in atherosclerosis, myocardial
      ischemia/reperfusion injury, and heart failure. Antioxidant enzymes are decreased
      in the decompensated heart, depressing defense mechanisms against oxidative
      stress. A variety of proteins, including receptors, ionic channels, transporters,
      and components of signal transduction pathways, are substrates of oxidation by
      ROS. ROS also function as signal transduction intermediates to induce
      transcription factor activation, gene expression, cell growth, and apoptosis.
      Recently, the upstream and downstream molecules of ROS in signal transduction
      pathways have been the subjects of intense investigation. These molecules include
      the mitogen-activated protein kinase family, the Rho family of small GTP binding
      proteins, the Src family of tyrosine kinases, Ras, and cytokines. The modulation
      of oxidative stress-induced signaling pathways is effective for preventing the
      progression of heart diseases.

PMID- 14588153
TI  - Redox regulation by thioredoxin in cardiovascular diseases.
AB  - Increasing evidence has indicated that the modulation of intracellular redox
      states has important aspects to cellular events, such as cellular proliferation,
      activation, growth inhibition, or death via the regulation of intracellular
      signal transduction and gene expression. Thioredoxin (TRX) is a multifunctional
      stress-inducible protein, which protects cells from various types of stresses.
      TRX has not only a scavenging activity of reactive oxygen species, but also a
      regulating activity of various intracellular molecules including transcription
      factors. We demonstrated that the serum TRX levels are correlated with the
      severity of heart failure, and are negatively correlated with left ventricular
      ejection fractions of patients with heart failure. The expression of TRX is
      enhanced in endothelial cells and macrophages in human atherosclerotic plaques,
      in balloon-injured rat arteries, and in damaged cardiomyocytes of rats with acute
      myocarditis. Overexpression of TRX in transgenic mice attenuates adriamycin
      induced cardiotoxicity by reducing oxidative stresses. These findings suggest
      that TRX and the redox system modulated by TRX have an important role in cellular
      defense against oxidative stress in cardiovascular diseases.

PMID- 14588154
TI  - Role of NADPH oxidases in the control of vascular gene expression.
AB  - All vascular cells, including endothelial cells and smooth muscle cells, express
      components of the leukocyte NADPH oxidase such as p22phox, p47phox, and Rac.
      Endothelial cells and fibroblasts also express the leukocyte NADPH oxidase
      subunit gp91phox/nox2, whereas in smooth muscle cells nox1 and nox4 are found.
      The different vascular NADPH oxidases represent important sources for the basal
      as well as the agonist-induced superoxide anion (O(2) .-) generation in the
      vasculature. In vascular smooth muscle cells, activation of the NADPH oxidases
      and the subsequent formation of O(2) .- has been demonstrated for various agents
      including angiotensin II, thrombin, lysophosphatidylcholine, and tumor necrosis
      factor alpha. By influencing the activity of p38 mitogen-activated protein kinase
      and AKT, NADPH oxidase-derived O(2) .- increases the expression of several pro
      arteriosclerotic genes, such as monocyte chemoattractant protein-1, tissue
      factor, and vascular endothelial growth factor. Thus, the vascular NADPH oxidases
      play an important role in mediating the signal transduction cascade of pro
      arteriosclerotic stimuli.

PMID- 14588156
TI  - Academic apoptosis.

PMID- 14588157
TI  - A prospective randomized study of clinical assessment versus computed tomography
      for the diagnosis of acute appendicitis.
AB  - BACKGROUND: The objective of this study was to determine if routine use of
      computed tomography (CT) for the diagnosis of appendicitis is warranted. METHODS:
      During a one-year study period, all patients who presented to the surgical
      service with possible appendicitis were studied. One hundred eighty-two patients
      with possible appendicitis were randomized to clinical assessment (CA) alone, or
      clinical evaluation and abdominal/pelvic CT. A true-positive case resulted in a
      laparotomy that revealed a lesion requiring operation. A true-negative case did
      not require operation at one-week follow-up evaluation. Hospital length of stay,
      hospital charges, perforation rates, and times to operation were recorded.
      RESULTS: The age and gender distributions were similar in both groups. Accuracy
      was 90% in the CA group and 92% for CT. Sensitivity was 100% for the CA group and
      91% for the CT group. Specificity was 73% for CA and 93% for CT. There were no
      statistically significant differences in hospital length of stay (CA = 2.4 +/-
      3.2 days vs. CT = 2.2 +/- 2.2 days, p = 0.55), hospital charges (CA = 10,728 US
      dollars +/- 10,608 vs. CT = 10,317 US dollars +/- 7,173, p = 0.73) or perforation
      rates (CA = 6% vs. CT = 9%, p = 0.4). Time to the operating room was shorter in
      the CA group, 10.6 +/- 8.4 h vs. CT, 19.0 +/- 19.0 h (p < 0.01). CONCLUSIONS:
      Clinical assessment unaided by CT reliably identifies patients who need operation
      for acute appendicitis, and they undergo surgery sooner. Routine use of
      abdominal/pelvic CT is not warranted. Further research is needed to identify sub
      groups of patients who may benefit from CT. Computed tomography should not be
      considered the standard of care for the diagnosis of appendicitis.

PMID- 14588158
TI  - Biliary tract infection in patients with acute biliary pancreatitis.
AB  - BACKGROUND: The presence of infective microorganisms in the bilio-pancreatic
      tract is believed to be important in both the onset and outcome of acute biliary
      pancreatitis. In this study, the characteristics of bile colonization or
      infection in human pancreatitis were investigated in order to optimize
      prophylactic antibiotic therapy. METHODS: In 174 patients, 22 clinical and
      biological factors were recorded prospectively on admission and compared with the
      bacteriological findings at the time of surgery. RESULTS: There was a significant
      difference between patients with negative or positive bile cultures in six
      parameters: Age (57.7 +/- 1.7 vs. 68.5 +/- 1.5 years, p < 0.001), serum
      concentrations of glucose (132 +/- 4 vs. 149 +/- 6 mg/dL, p < 0.02) and alanine
      aminotransferase (ALT) (304 +/- 28 vs. 226 +/- 25 IU/L, p < 0.05) and hematocrit
      (43.4 +/- 0.4% vs. 41.7 +/- 0.5%, p < 0.05), Glasgow pancreatitis score (1.58 +/-
      0.11 vs. 1.97 +/- 0.10, p < 0.01) and APACHE II score (6.20 +/- 0.38 vs. 7.82 +/-
      0.35, p < 0.005). The prediction of the presence of bacteria in bile by each of
      these individual parameters, however, was of variable accuracy. From 82 patients
      with positive bile cultures, a total of 150 microorganisms were isolated,
      including 66 gram-positive aerobes, 66 gram-negative facultative anaerobes, 15
      obligate anaerobes, and three fungi. The most common organisms were Escherichia
      coli (20.6%), followed by enterococci (18%) and streptococci (15.3%). CONCLUSION:
      Patients with acute biliary pancreatitis who manifest abnormalities of one or
      more of the above-mentioned risk factors are more likely to have positive bile
      cultures. Whether such patients might benefit from early antibiotic therapy
      directed against both gram-negative bacilli and gram-positive cocci needs to be
      determined.

PMID- 14588159
TI  - The severity of infection induces a shift in the type 1/Type 2 T-helper cell
      balance in patients with or without peritonitis.
AB  - BACKGROUND: A type-1 to type-2 T-helper cell (Th1/Th2) shift is hypothesized to
      occur among patients with severe trauma and pancreatitis. It was hypothesized
      that the Th2 situation caused an immune-suppressed period that led to a critical
      imbalance in the patients' conditions, with an increased risk of multiple organ
      failure and mortality. METHODS: In eight patients with localized intra-abdominal
      infection (diverticulitis) and six patients with peritonitis due to perforation
      of a hollow viscus, we examined the cytokine response of CD3(+) T cells in the
      greater omentum and in the peripheral blood by in vitro stimulation,
      intracellular cytokine staining, and flow cytometry for TNF-alpha, IFN-gamma, IL
      2, and IL-4. Follow-up cytokine assays were carried out on peripheral blood on
      days 3 and 7. Different levels of cytokine expression in each group were examined
      to determine the origin of the lymphocytes, both from omentum or peripheral
      blood. Cytokine production in the diverticulitis group was compared with that of
      the peritonitis patients. RESULTS: In localized infections (diverticulitis),
      there was higher expression of TNF-alpha (51%/35% positive cells in
      omentum/blood), IFN-gamma (47%/32%), and IL-2 (33%/20%) in the omentum than in
      the peripheral blood mononuclear cells (PMBCs), but this was not true for IL-4
      expression (0.8%/1.3%). In patients with peritonitis, there were no differences
      in cytokine expression between lymphocytes from the greater omentum and from
      PMBCs for TNF-alpha (18%/21% omentum/blood), IFN-gamma (20%/22%), IL-2 (16%/12%),
      or IL-4 (10.9%/7.6%). Compared to the diverticulitis group, patients with
      peritonitis showed reduced expression for TNF-alpha, IFN-gamma, and IL-2, but
      there was a significantly higher response for IL-4 for both compartments.
      CONCLUSIONS: There was a shift from Th1 to Th2 in patients with severe clinical
      symptoms of peritonitis. Immune suppression is evident because of the T cell
      response in the greater omentum, but immunosuppression seems to not reach its
      maximum level before day 7 post operation. This differs from findings in multiple
      trauma and pancreatitis; however, it is parallel to the clinical situation in
      patients with peritonitis.

PMID- 14588161
TI  - Fungal infections in solid organ transplant patients.
AB  - BACKGROUND: Solid organ transplantation is becoming increasingly more common in
      the treatment of end-stage organ failure. Opportunistic fungal infections are a
      frequent life-threatening complication of transplantation. MATERIALS AND METHODS:
      In this article, a review of the infections in the different organ transplant
      recipients is presented. RESULTS: The incidence of fungal infections in organ
      transplant patients ranges from 2% to 50% depending on the type of organ
      transplanted, kidney recipients being the least frequent and liver recipients
      having the highest rate of infection. New antifungal medications and
      immunosuppressants have changed the spectrum of fungal treatment and prevention.
      CONCLUSION: Prompt recognition and treatment of infection is imperative for
      successful therapy. Further advancements in early detection and the development
      of less toxic medications will lead to refinements in the treatment of fungal
      infections.

PMID- 14588160
TI  - In vitro antimicrobial activity of oxidized regenerated cellulose against
      antibiotic-resistant microorganisms.
AB  - BACKGROUND: The emergence of multi-drug resistant microorganisms presents a
      critical problem for patients undergoing surgery. Acidic pH, which is produced by
      oxidized regenerated cellulose (ORC), is a broad-spectrum physiological detriment
      to survival of microorganisms known to cause surgical infections. The purpose of
      this study was to examine the antimicrobial effect of ORC against antibiotic
      resistant organisms. METHODS: ORC products were challenged with ATCC reference
      strains and clinical isolates of methicillin-resistant Staphylococcus aureus
      (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE), vancomycin
      resistant Enterococcus (VRE), penicillin-resistant Streptococcus pneumoniae
      (PRSP), and non-resistant ATCC strains of S. aureus and Pseudomonas aeruginosa.
      Samples of three ORC products (SURGICEL absorbable hemostat, SURGICEL Fibrillar
      absorbable hemostat, and SURGICEL NU-KNIT absorbable hemostat and identified,
      respectively, as ORC-R, ORC-F, and ORC-N for this study) were inoculated with
      challenge organisms in nutrient broth to produce a weight to volume ratio of 15
      mg ORC/mL. Plate counts were performed at 0, 1, 6, and 24 h. RESULTS:
      Antimicrobial activity was seen with all three ORC products against the challenge
      organisms. Data indicate that antibiotic-resistant microorganisms remain
      susceptible to the antimicrobial activity of ORC. In testing with nine of 10
      bacteria, including four antibiotic-resistant clinical isolates (VRE, MRSA, and
      PRSP) three-log or greater reductions were seen at 24-h exposure. One ATCC strain
      of VRE demonstrated some level of resistance to the acidic pH effect. ORC-N
      showed a three-log reduction with this organism, whereas the reductions with ORC
      R and ORC-F were less than one log. CONCLUSION: Since low pH affects a relatively
      broad-spectrum of bacteria and does not act in a mechanism-specific manner, as do
      antibiotics, antibiotic-resistant strains of bacteria are unlikely to resist the
      ORC pH effect. Results of this in vitro assessment support the hypothesis that
      the antimicrobial activity of ORC is effective against antibiotic-resistant
      microorganisms.

PMID- 14588162
TI  - Prophylaxis of infection for elective colorectal surgery.
AB  - BACKGROUND: Influenced by the key results of the clinical trials conducted in the
      early 1970s by Condon, Nichols, and Gorbach, surgeons have adopted the routine
      use of mechanical bowel prep and antimicrobial prophylaxis prior to elective
      colorectal procedures as a widely established practice. Recent clinical trial
      data, however, led us to reexamine the benefits of mechanical bowel preparation,
      methods of antimicrobial prophylaxis and to assess the role of new, specific risk
      factors for surgical site infection after colorectal operations. METHODS:
      Pertinent studies on antimicrobial prophylaxis for elective colorectal surgery
      were identified from a Medline search of English language publications since
      1966. RESULTS: We found credible clinical trial data that mechanical bowel
      preparation prior to elective colorectal surgery may not be essential. Timing of
      the administration of prophylactic antimicrobials is often inaccurate in current
      practice and suggests the need for a long-acting, broad-spectrum agent that would
      deemphasize precision in time of preoperative infusion. New risk factors have
      been identified that increase infection after colorectal surgery, including
      patient core temperature and tissue oxygenation. Independent observers identify
      postoperative surgical site infection at a higher rate than physician self
      reporting and should be incorporated into future clinical trials. CONCLUSION: The
      once settled area of antimicrobial prophylaxis for colorectal surgery is again
      controversial. Cooperative clinical trials will be needed to resolve key
      questions such as the efficacy for bowel preparation and how to obtain effective
      timing of antimicrobial prophylaxis.

PMID- 14588164
TI  - Vancomycin-resistant Enterococcus ventriculo-peritoneal shunt infection cured by
      monotherapy with chloramphenicol.

PMID- 14588163
TI  - Bacterial agents used for bioterrorism.
AB  - BACKGROUND: Bacterial pathogens and their products are potential agents of
      biological terrorism and biological warfare. These agents can be deployed through
      simple aerosol delivery systems and thereby cause widespread disease and death.
      METHODS: This report is a review of bacterial species that have been employed for
      development of biological terrorism, relying on a system for classification of
      their threat developed by the Centers for Disease Control. RESULTS: Physicians
      must understand how to recognize early signs and symptoms caused by bacterial
      agents. Clinical findings often seen on presentation are emphasized along with a
      summary of therapeutic approaches. CONCLUSIONS: Initiation of immediate therapy
      and supportive care provides the best chance for survival from these potentially
      lethal and devastating infections. A high index of suspicion must be maintained,
      especially in the setting of a sudden influx of cases with what are often
      relatively nonspecific symptoms.

PMID- 14588165
TI  - Helicobacter pylori: a diverse bacterium.

PMID- 14588166
TI  - Endoscopic dilation of esophageal strictures.
AB  - OBJECTIVE: To review the experience of endoscopic dilation of esophageal
      strictures at a tertiary care hospital. DESIGN: Descriptive study. PLACE AND
      DURATION OF STUDY: Shifa International Hospital, Islamabad January 1985 to
      January 2003. MATERIALS AND METHODS: Patients presenting with dysphagia who
      presented at our institution during the past 8 years were reviewed. Their
      etiology and the number of dilations required for improvement in dysphagia and
      follow up with any complications were reviewed. All procedures were performed
      with savary dilators using guide wire without fluoroscopy. RESULTS: A total of
      369 patients were seen during this period and 583 procedures were performed. Two
      hundred thirty-five (63.7%) patients had peptic stricture, 123 (33.3%) had
      malignant strictures, 08 (2.2%) had non obstructive dysphagia and 6 (1.6%) had
      corrosive ingestions. The age ranged from 28-68 years. There were 254 (88.5%)
      males and 115 (31.2%) females. Sixty-seven (11.5%) procedures were performed as
      inpatient and 516 (88.5%) procedures were done as outpatient. Two to three
      attempts at dilatation were required to achieve satisfactory swallowing. There
      were no serious complication. Follow-up period was 6-8 weeks on an average.
      CONCLUSION: Most common esophageal stricture found in our practice were peptic
      strictures. Dilation with savary system was safe and effective and was able to
      relieve dysphagia in large number of patients. No fluoroscopic guidance was
      needed.

PMID- 14588167
TI  - Role of health education in the management of diabetes mellitus.
AB  - OBJECTIVE: To evaluate the level of awareness of diabetic patients about their
      disease; and to see the association between different levels of this knowledge
      and metabolic control and frequency of complications in patients with diabetes
      mellitus. DESIGN: An observational analytical study. PLACE AND DURATION OF STUDY:
      The study was conducted in the Department of Medicine, Postgraduate Medical
      Institute, Lady Reading Hospital, Peshawar, from May 20, 2000 to November 20,
      2000. SUBJECTS AND METHODS: A total number of 100 patients, 35 males and 65
      females, 28 with type-1 and 72 with type-2 diabetes mellitus (DM) were included
      in the study. The ages of the patients ranged from 21 to 80 years with mean age
      of 48.75 years + 12.43 standard deviations (SD). A questionnaire was designed
      comprising of 24 different aspects of DM. The patients were grouped into three
      categories on the basis of their awareness and level of knowledge about their
      disease. Statistical analysis of the results was made by applying student s t
      test on mean scores of the knowledge of diabetes and the glycemic control, as
      reflected by the mean HbA1c, at significance at p<0.05, whereas Chi-square test
      was applied at frequency of complications. RESULTS: Fifty-eight percent of all
      the patients were in category 1 with inadequate knowledge (mean score 3.7) who
      had poorly controlled DM with mean HbA1c of 9.94% and higher rates of
      complications (89.6%) whereas 20% of the patients were in category 3, having
      adequate knowledge (mean score of 19.9), had good control of their disease (mean
      HbA1c=7.88%) and lower frequency (40%) of complications. CONCLUSION: The
      awareness about the disease in majority of diabetic patients, was not adequate in
      this study. An adequate knowledge of the disease through health education is
      associated with good metabolic control and prevention of complications associated
      with diabetes mellitus and its therapy.

PMID- 14588168
TI  - Outcome of chemoradiation in treating carcinoma esophagus.
AB  - OBJECTIVE: To observe the role of chemoradiation in treating carcinoma of
      esophagus, its complications and outcome of disease. DESIGN: Analytical
      descriptive study. PLACE AND DURATION OF STUDY: Conducted at IRNUM in
      collaboration with Hayatabad Medical Complex (HMC), Peshawar, for one year.
      PATIENTS AND METHODS: A total of 47 males and 53 females with an average age of
      53 +/- 13 years were inducted in this study. Patients having upper end carcinoma
      or esophageal surgery were excluded from this study. They were treated with radio
      as well as chemotherapy. Those patients who had completed radiation six months
      before were planned for repeat endoscopies. Response evaluation was categorized
      as no evidence of disease, residual disease or stricture formation simulating
      carcinoma. Seventy percent of endoscoped patients were disease free and 30% were
      having residual disease. Of these 30%, 10% were having growth while rest of the
      20% showed stricture formation due to radiation. RESULTS: Out of 100 patients,
      70% were palliated maximally and no evidence of disease was found on endoscopy
      done after 1-6 months. Only 30% came up again with dysphagia. Out of these 30%,
      20% were having esophageal stricture, which on dilatation improved the quality of
      life. Rest of the 10% were having stricture hiding the residual disease. Giving 1
      2 cycles of chemotherapy before the start of radiation reduced the disease burden
      and predicted response to radiation by improving dysphagia. CONCLUSION: In spite
      of certain complications like neutropenia, emesis and stricture formation,
      chemoradiation is still the best treatment option available. It is because of its
      safety, well-tolerability and cost effectiveness. It is equally good for patients
      who refuse surgery and those with advanced disease.

PMID- 14588169
TI  - Complications of the surgery for deviated nasal septum.
AB  - OBJECTIVE: To find out the causes of complications arising due to nasal septal
      corrective surgery. DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: The
      study was carried out at the Department of Otorhinolaryngology, Head and Neck
      Surgery, Civil Hospital, Karachi, from 1997-1999. SUBJECTS AND METHODS: A total
      of 200 cases from all age groups of both genders with symptomatic deviated nasal
      septum (DNS) without allergic rhinitis were selected. One hundred sixty-two
      patients were males and 38 were females. All of them were subjected to nasal
      septal surgery as per situation. Septoplasty was performed in patients below 15
      years of age with caudal septal dislocation and adults with minimal deviation
      confined to cartilagenous septum. Classical submucous resection (SMR) was
      performed in most other cases. A record was maintained in the outpatient Clinic
      in which the observations and findings of these patients, visiting for follow-up
      were entered for more than a year. RESULTS: SMR alone was performed in 96 cases
      (48%). SMR with bilateral antral washout in 35 cases (17%). SMR with submucosal
      diathermy and without fracture of inferior turbinate was done in 4 cases each
      (2%). Conservative septal surgery (septoplasty) was performed in 48 cases (24%).
      Septorhinoplasty was carried out in 13 cases (6.5%) with external nasal deformity
      due to severe deflection of nasal septum. In 50 cases (25%) intranasal splints
      were kept after the nasal septal surgery. The results of the surgical procedures
      were assessed clinically. The overall incidence of complications was septal
      perforation in 10 cases (5%), adhesions in 14 cases (7%), recurrence of symptoms
      or deformity in 12 cases (6%), saddle nose deformity in 2 cases (1%), and
      columellar retraction with loss of tip projection was found in 2 cases (1%).
      Palatal perforation was also observed in 2 patients which was repaired primarily
      and excellent healing occurred postoperatively. The incidence of complications
      was 21% and it was higher in classical submucosal resection than after
      septoplasty. CONCLUSION: Complications are related to the type of procedure
      performed. More complications are seen with classical SMR. Adhesions are common
      complication if intranasal splint is not provided.

PMID- 14588171
TI  - Mortality variables in pyogenic meningitis in paediatric age group.
AB  - OBJECTIVE: To determine the association of the studied variables on mortality in
      pyogenic meningitis in paediatric age group. DESIGN: An observational analytical
      study. PLACE AND DURATION OF STUDY: Paediatrics Medicine, Unit-2 of B.V.
      Hospital, attached with Quaid-e-Azam Medical College, Bahawalpur, from December
      2000 to December 2002. PATIENTS AND METHODS: Sample size was 300 admitted cases
      of pyogenic meningitis, aged 2 months to 12 years, meeting the inclusion
      criteria. The association of the different variables with mortality in pyogenic
      meningitis was studied. Data was collected and tabulated. X2 test of significance
      was applied to determine the p-value. p<0.05 was taken as statistically
      significant. RESULTS: The mortality rate was 10% (30/300). The association of
      different variables, with outcome at the time of admission was statistically
      significant in prolonged duration of illness (chronicity prior to admission and
      increased cerebrospinal fluid (CSF) neutrophils after 1st lumbar puncture. Among
      the etiological microorganisms isolated from culture of CSF, only Streptococcus
      pneumoniae had statistically significant association. CONCLUSION: Mortality in
      pyogenic meningitis was significantly related to pre-admission illness duration
      and CSF neutrophilia. Mortality can be reduced by early and appropriate
      recognition. Antibiotic and supportive therapy should be initiated promptly
      followed by specific medication when the reports of the CSF culture is available.

PMID- 14588170
TI  - Outcome of macular hole surgery.
AB  - OBJECTIVE: To document the outcome of macular hole surgery in terms of
      improvement of visual acuity and the duration of closure of macular hole. DESIGN:
      Interventional quasi experimental study. PLACE AND DURATION OF STUDY:
      Ophthalmology Department, Civil Hospital, Karachi. SUBJECTS AND METHODS: Twenty
      four eyes of 22 patients with macular hole underwent surgical repair. Vitrectomy
      with maculorrhexis (internal limiting membrane peeling) and fluid-gas exchange
      followed by prone positioning for one to two weeks was carried out. Postoperative
      follow-up was done for one year. Main outcome measures were visual acuity,
      closure of macular hole and ocular complications. Data was analyzed by using SPSS
      Version 10. Non-parametric sign test with chi-square statistic was used to
      compare the pre-operative and postoperative outcome. RESULTS: The macular hole
      was successfully closed in 17 eyes that revealed high statistical significance
      regarding improvement in visual acuity. Earlier, significant improvement figured
      in 17/24 cases was observed at three-month post-operative examination (p<0.0001).
      An insignificant success figured in 8/24 due to postoperative complications at
      six-month follow-up. Visual acuity improved upto two or more lines in 17 eyes at
      one-year follow-up. Twelve cases developed cataract, 7 developed increased intra
      ocular pressure (transient), one had glaucoma and one retinal detachment.
      CONCLUSION: Vitrectomy with maculorrhexis (internal limiting membrane peeling)
      and fluid-gas exchange can successfully close macular holes and improve vision.

PMID- 14588172
TI  - Utility of thick smears of bone marrow aspirate in pyrexia of unknown origin.
AB  - OBJECTIVE: To determine the diagnostic efficacy of Giemsa stained thick smear of
      bone marrow aspirate for evidence of malaria in febrile individuals in whom the
      diagnosis was otherwise unknown. DESIGN: Descriptive case-series study. PLACE AND
      DURATION OF STUDY: This study was conducted at the Department of Medicine,
      Sandeman Provincial Hospital, Quetta, in the Balochistan province of Pakistan,
      between January 1994 and December 1998. SUBJECTS AND METHODS: A total of 80
      patients were included in the study, who presented with history of fever for more
      than 3 weeks with splenomegaly and pancytopenia. The bone marrow specimens of all
      these patients were examined. The bone marrow was aspirated from the posterior
      superior iliac spine. Three sets of smears were made. One set of thin smears was
      stained by Leishman's stain after air-drying and the second set of thin smears
      was air-dried, fixed with 97% methanol and later stained with 5% Giemsa stain.
      The third set of smears was a thick smear stained unfixed with 5% Giemsa stain. A
      temperature of 37 degrees C and a pH of 7.2 was maintained during the staining
      process. The presence of malarial parasite in the bone marrow was determined.
      Besides, the degree of megaloblastic change in erythroid series and the bone
      marrow cellularity were evaluated. The results obtained were recorded and
      statistically analyzed. RESULTS: Of the 80 bone marrows examined, 32(40%) showed
      the presence of malarial parasites, 19(23.75%) showed haematological
      malignancies, 16(20%) showed bone marrow suppression while 12(15%) showed
      megaloblastic changes. One (1.25%) case showed Leishman-Donovan bodies. Out of 32
      cases showing the presence of malarial parasite in bone marrow, only 5(15.6%)
      revealed parasites, i.e. Plasmodium falciparum gametocytes on thin smear while
      32(100%) cases showed Plasmodium falciparum trophozoites and gametocytes on thick
      smear. The ratio was 1:6.4. These 32 patients were divided into two groups, one
      group having mild anaemia (>8 g/dL) and the other severe anaemia (Hb<8 g/dL). In
      this study 20 patients had mild and 12 had severe anaemia. Megaloblastic changes
      were seen in 15 cases. Hypocellularity was seen in 3 patients with falciparum
      malaria while 28 showed normocellularity. The marrow was hypercellular in one
      patient. CONCLUSION: In patients presenting with prolonged fever, splenomegaly
      and pancytopenia, the Giemsa stained thick smear of bone marrow aspirates for
      evidence of malarial parasites was far superior to thin smear in diagnosing
      Plasmodium falciparum malaria.

PMID- 14588173
TI  - Obsessive compulsive disorder in a fishermen community.
AB  - OBJECTIVE: To find the prevalence of obsessive compulsive disorder(OCD). DESIGN:
      Cross-sectional study. PLACE AND DURATION OF STUDY: Two years at the local
      community of Manora, Karachi. SUBJECTS AND METHODS: An initial survey was
      conducted in a fishermen community at Salehabad which is located in Manora. A
      questionnaire inquiring about the demographic details of the patients and using
      the ICD-10 diagnostic research criteria along with Yale-Brown OC scale on a
      population of 5,000 for a period of 2 years was applied. About 150 positive cases
      were identified whose details were subjected to analysis. RESULTS: Out of a total
      population of 5,000, 3% were found to be suffering from OCD. Among these 56%
      (n=150) were females, 60% were married and 50% of the cases were under the age of
      25. Among the obsessions contamination, pathological doubt and need for symmetry
      were the most common. Regarding the compulsions, checking, washing and counting
      were the most common. CONCLUSION: It was concluded that 3% of the population of
      given community was suffering from OCD, which is a significant finding. More
      community based studies are needed to assess the real magnitude of this illness.

PMID- 14588174
TI  - Role of fixateur interne in thoracolumbar junction injuries.
AB  - OBJECTIVE: To evaluate the use of fixateur interne in thoracolumbar junction
      injuries. DESIGN: An interventional descriptive study. PLACE AND DURATION OF
      STUDY: This study was conducted in the Department of Neurosurgery, PIMS from
      September 1996 to September 2001. PATIENTS AND METHODS: Seventy-nine patients
      with posttraumatic instability of lower thoracic or upper lumbar spine were
      surgically managed. Frankel grading was used to determine the neurological status
      of the patients. White and Panjabi criteria was used to determine the instability
      of the spine. All the patients with unstable spine undergoing surgery were
      included in the study. Open reduction and internal fixation using fixateur
      interne was done in all the cases. Changes in neurological status and
      complications were noted postoperatively and on subsequent follow-ups. RESULTS:
      Most of the patients undergoing surgery were young. The commonest mode of trauma
      was due to fall in 59 patients. None deteriorated postoperatively. Initially,
      there were only 19 patients in Frankel E whereas at 1-year follow-up, there were
      27 patients in Frankel E. On an average, there was 0.9 Frankel improvement.
      Average blood loss in an operation was 250 ml, average time for operation was 70
      minutes and the average postoperative hospital stay was 7.9 days. There were 02
      (2.5%) implant failures and their implants were removed. There were 02 (2.5%)
      cases of wound infection. The hardware was removed in one patient while in the
      other, the infection was controlled with antibiotics and wound debridement alone.
      CONCLUSION: Fixateur interne may be useful choice for achieving reduction and
      stability in most thoracolumbar injuries for early ambulation and faster
      recovery.

PMID- 14588175
TI  - Unilateral exploration for primary hyperparathyroidism.
AB  - OBJECTIVE: To examine the efficacy of using pre-operative imaging studies (Sesta
      MIBI scan and ultrasonography) to localize the pathology and allow for unilateral
      neck exploration to assess its safety. DESIGN: Descriptive analytical study.
      PLACE AND DURATION OF STUDY: Department of Surgery/ENT, Pakistan Institute of
      Medical Sciences (PIMS), Islamabad. SUBJECTS AND METHODS: Twenty-three patients
      were reviewed, who underwent operation for primary hyperparathyroidism (PHPT) in
      our institution between 1995 and 2002. A total of 49 enlarged parathyroid glands
      were removed. Patients were divided into two groups. In group-A (in which only
      unilateral exploration was done) there were 21 patients (42 glands). In group-B,
      bilateral exploration was done, which included 2 patients and 7 glands. Sesta
      MIBI scan and ultrasonography were done in all cases. Results were analyzed
      statistically with appropriate tests of significance. RESULTS: Sesta-MIBI scan
      showed an accuracy of 91% (20 adenomas) whereas ultrasound was positive in 18
      patients (78%). One case of adenoma and 2 cases of hyperplasia were not detected
      by pre-operative imaging. Unilateral exploration of neck was successful in 19
      cases of adenoma. The parameters used for successful exploration were corrected
      serum calcium and parathyroid hormone levels. Ultrasound was positive in 18
      patients (78%). There was a significant difference in surgical time between the
      unilateral and bilateral neck explorations (45 minutes). Unilateral neck
      exploration for hyperparathyroidism has been successful in curing hypocalcaemia
      22/23(95%). CONCLUSION: At least two pre-operative localization tests, a Sesta
      MIBI scan and ultrasonography, should be done for accurate localization of an
      abnormal parathyroid gland especially adenoma. Selective unilateral exploration
      is safe and reliable if the second ipsilateral gland is normal macroscopically or
      microscopically.

PMID- 14588177
TI  - Functional outcome of Horton's vaginoplasty.
AB  - OBJECTIVE: To describe the functional results of Horton's vaginoplasty. DESIGN: A
      descriptive study. PLACE AND DURATION OF STUDY: Department of Plastic Surgery,
      Hayatabad Medical Complex, Peshawar. The duration of study was three years from
      May 1998 to May 2001. SUBJECTS AND METHODS: During the three years period, 17
      patients were operated with congenital vaginal agenesis. Horton's vaginoplasty
      with full thickness skin grafts was performed in all these patients. Patients
      with a follow-up of less than 6 months were excluded from the study. Sexual
      assessment was done in married patients after Horton's vaginoplasty. These
      patients were categorized into four categories according to their sexual
      experience. RESULTS: Functional assessment revealed excellent sexual relations in
      36.36%, good in 45.45% and satisfactory in 18.18% patients. Vaginal stenosis and
      loss of graft take was observed in 5.8% patients. The average depth of vagina was
      8.5 cm. The width was two fingers in 64.70% and three fingers in 29.41% patients.
      CONCLUSION: Horton's vaginoplasty is a versatile, single-stage procedure, with
      minimal donor site morbidity. The reconstructed vagina is excellent both in
      function and cosmesis.

PMID- 14588176
TI  - Effects of diet on body weight, haemoglobin, serum proteins and trace elements in
      burned children.
AB  - OBJECTIVE: To compare the effect of two diets on serum proteins, trace elements,
      haemoglobin and body weight in burned children. DESIGN: Comparative analytical
      study. PLACE AND DURATION OF STUDY: The study was conducted on burned children
      admitted in Nishtar Ward, Allied Hospital, Faisalabad for seven months, from
      February to August 2002. MATERIALS AND METHODS: The study was conducted on 61
      children of 3-14 years of age. Of these, 27 children were randomly selected and
      advised diet 1 (vegetables and milk-rich diet), while 34 children were randomly
      selected and advised diet 2 (pulses and egg-rich diet). Serum proteins and
      haemoglobin were determined spectrophotometrically, trace elements by atomic
      absorption spectrophotometric methods and body weight by weighing machine. The
      data obtained was analyzed statistically on SAS 6.12. RESULTS: During the study,
      30 percent children died. Relatively higher deaths occurred in children advised
      vegetables + milk-rich diet. The increase in body weight was noted in 25 %
      children. Of these, significant number was in those advised pulses + eggs rich
      diet (p<0.01). The haemoglobin, total proteins, albumin, globulins, copper and
      zinc showed no change. Haemoglobin (p<0.01) and serum total proteins (p<0.05)
      increased in significantly higher percentage of children advised diet 2. Decrease
      in serum globulins and no change from initial values were comparable in two
      diets, while the increase was in relatively higher percentage of children advised
      diet 2. The decrease in serum copper was almost in same percentage of children
      advised two diets. It was maintained in relatively higher percentage of children
      advised diet 1. However, the increase in serum copper was in significantly
      (p<0.05) higher percentage of children advised diet 2. Serum zinc maintenance was
      in significantly (p<0.001) higher percentage of children advised rich diet 2.
      CONCLUSION: Better effect of pulses and eggs rich diet in burned children was
      seen on the basis of parameters studied. However, the role of vegetables and milk
      in burned children has not been ruled out altogether.

PMID- 14588178
TI  - Efficacy of thoracoscopic lung biopsy in interstitial lung diseases: comparison
      with open lung biopsy.
AB  - OBJECTIVE: To determine the efficacy of video-assisted thoracoscopic surgery
      (VATS) compared to open lung biopsy. DESIGN: Descriptive, observational case
      series. PLACE AND DURATION OF STUDY: The Cardio-thoracic Centre, Liverpool, UK,
      from January 1995 to December 1999. PATIENTS AND METHODS: One hundred consecutive
      patients, undergoing lung biopsy for interstitial lung disease during this
      period, were included in the study. Thirty patients underwent open lung biopsy,
      while 70 patients had VATS lung biopsy. Patient characteristics, site, size,
      number and laterality of biopsy, complications, morbidity, mortality and
      diagnostic yield was compared. P-value was determined to assess significance of
      findings. Statistical analysis was performed on SAS for windows version 8.
      RESULTS: Seventy-five percent had diagnostic yield in VATS group, while 37% in
      open group (p=0.04). Mean FEV1 was 3.2 litre in VATS group and 1.92 litre in open
      group (p=0.05). Right side was selected in 58.6% in VATS group and 36.7% in open
      group (p =0.04). Right lower lobe was the main site for biopsy in the VATS group
      compared to open group (18.6% versus 3.3%, p=0.04). Mean volume of biopsy was
      15.6 cm3 in VATS group and 12.5 cm3 in open group (p=0.04). Two or more biopsies
      were carried out in 37.1% of the VATS group compared to 16.7% of the open group
      (p=0.04). Chest drain duration was in 1 day in VATS group compared to 2 days in
      open group (p=0.01). Length of stay was 3 days in VATS group and 4 days in open
      group (p=0.003). CONCLUSION: Patients undergoing thoracoscopic lung biopsy had a
      significantly reduced chest drain duration and post-operative length of stay.
      Thoracoscopic lung biopsy is beneficial in determining a diagnostic yield with an
      advantage of greater volume and selection of biopsy sites.

PMID- 14588179
TI  - Primary tuberculosis of tongue.
AB  - A case of a 55 years old lady with tuberculosis of the tongue is reported.
      Patient presented with non-healing ulcer in dorsum of the tongue for one year.
      Initial biopsy and histopathological examination revealed non-specific
      inflammation. After surgery, biopsy report proved primary tuberculosis of tongue.
      Anti-tubercular therapy for nine months showed uneventful recovery of the
      patient.

PMID- 14588180
TI  - What next after hormonotherapy in cancer prostate?
AB  - Treatment of hormone-resistance cancer prostate (HRCP) is undergoing evolution.
      Chemotherapy is now increasingly being utilized. The steps involved in the
      hormone management and the role for chemotherapy in the current time are being
      discussed. Hormonal management is carried out at different stages of hormonal
      sensitivity by sequential hormonal use. Once hormonal resistance is established,
      the combination of mitoxantrone and prednisone become a standard chemotherapeutic
      approach. New agents, such as docetaxel, are being tested in phase-III trials
      against mitoxantrone plus prednisone. HRCP is now regarded as a chemotherapy
      sensitive tumor. The goals of chemotherapy in HRCP are to decrease PSA level and
      improve quality of life. New agents and combinations are needed to improve
      survival to meet this end.

PMID- 14588181
TI  - Unravelling the role of pineal gland.
AB  - The pineal gland has been classically considered as a vestigial organ with mystic
      properties. With the development of new methodical experiments, its physiologic
      actions are unravelled vary depending on the level of the phylogenetic scale.
      Since the discovery of melatonin as the principal hormone of the pineal gland, is
      an important hormone involved in the control of circadian rhythms and other
      diverse biological functions. Recent metabolic, receptor and functional studies
      have discovered melatoninergic system(s) in living organisms, its organization,
      physiology and a role in some pathologic conditions. The melatonin-generating
      system is characterized by three basic features: (1) photosensitivity, (2)
      diurnal (or circadian) rhythmicity (with highest levels of melatonin production
      occurring at night in darkness), and (3) age-related decline in its activity.

PMID- 14588182
TI  - Ethical issues in genetic research.

PMID- 14588183
TI  - Distribution of spermatozoa in the outer perivitelline layer from above the
      germinal disc of emu and ostrich eggs.
AB  - In the present study, we determined the distribution of spermatozoa in the
      perivitelline layer above the germinal disc (GD) of emu and ostrich eggs that had
      been laid at random intervals after mating. Eggs were opened, the perivitelline
      layer overlying the GD region was collected and sperm were visualized with 4',6'
      diamidino-2-phenylindole under a fluorescence microscope. To map the distribution
      of sperm, the GD was divided into six areas (A-F), with A being the centre of the
      GD and F the area furthest from the centre. In both species, more spermatozoa
      were found in areas B, C and D than in areas A, E and F. More than half the GD
      spermatozoa were found in areas B, C and D. The pattern of distribution of
      spermatozoa across the GD depended on the total number of sperm in the GD. In the
      emu, the pattern was related to delay since last copulation and time of laying,
      whereas in the ostrich the pattern was related to the month of the season and the
      sex ratio of the mating system. When the total number of spermatozoa in the GD
      increased, the number of spermatozoa increased in every area of the GD, but the
      centre and the outer areas were the least affected. We conclude that sperm
      numbers are highest in a band immediately around the centre of the GD and then
      decline with increasing distance from the centre. The low numbers in the centre
      of the GD may be due to either low attractiveness of the centre for sperm or high
      attractiveness of the area immediately adjacent to the centre.

PMID- 14588184
TI  - Steroid hormones augment nitric oxide synthase activity and expression in rat
      uterus.
AB  - Nitric oxide (NO) is synthesized in a variety of tissues, including rat uterus,
      from L-arginine by NO synthase (NOS), of which there are three isoforms, namely
      neuronal, endothelial and inducible NOS (nNOS, eNOS and iNOS, respectively).
      Nitric oxide is an important regulator of the biology and physiology of the
      organs of the reproductive system, including the uterus. Some studies have shown
      increased variation in NO production and NOS expression during the oestrous
      cycle. However, the factors that regulate NO production in the uterus remain
      unclear. Therefore, in the present study, we investigated the effect of sex
      steroids on NOS expression and activity in the ovariectomized rat uterus.
      Ovariectomized rats received progesterone (4 mg per rat) or 17beta-oestradiol (1
      microg per rat). All rats were killed 18 h after treatment. Both progesterone and
      oestradiol were able to augment NOS activity. The effect of oestradiol was
      abolished by pre-incubation with 500 micro M aminoguanidine, an iNOS inhibitor,
      or by coadministration of oestradiol with 3 mg kg(-1) dexamethasone, but the
      effect of progesterone was not affected by these treatments. Uterine nNOS, eNOS
      and iNOS protein levels were assessed using Western blots. Ovariectomized rat
      uteri expressed iNOS and eNOS. Progesterone increased the expression of eNOS and
      iNOS, whereas oestradiol increased iNOS expression only. These results suggest
      that oestradiol and progesterone are involved in the regulation of NOS expression
      and activity during pregnancy and implantation in the rat.

PMID- 14588186
TI  - Alkaline phosphatase activity in bovine oocytes and preimplantation embryos as
      affected by removal of the zona pellucida and culture medium constituents.
AB  - The aims of the present study were: (1) to characterize alkaline phosphatase (AP)
      activity in bovine oocytes and embryos with intact or removed zona pellucida
      (ZP); and (2) to evaluate the effect of culture medium constituents on AP
      activity. Alkaline phosphatase activity in non-matured and matured oocytes was
      most evident nearest the plasma membrane and perivitelline space. In more than
      90% of two- to 16-cell embryos, AP activity was observed in the perivitelline
      space and at blastomere contacts. In blastocysts, AP activity was localized to
      the trophectoderm. Only after immunodissection was AP activity detected in the
      inner cell mass. Removal of the ZP by pronase or mechanical means reduced AP
      activity. Alkaline phosphatase activity was detected in evacuated ZP after
      mechanical removal. Specific constituents comprising the embryo culture medium
      altered AP activity. Alkaline phosphatase activity was reduced in eight- to 16
      cell embryos and evacuated ZP cultured in CR1aa + 0.4% bovine serum albumin
      compared with embryos cultured in CR1aa alone or embryos co-cultured on a
      monolayer of Buffalo rat liver cells in the presence of 10% fetal bovine serum.
      The presence of AP activity at blastomere contacts and in evacuated ZP limits its
      usefulness as a marker for the differentiation of embryonic cells comprising the
      early cleavage-stage embryo.

PMID- 14588185
TI  - Consequences of exposure to serum, with or without vitamin E supplementation, in
      terms of the fatty acid content and viability of bovine blastocysts produced in
      vitro.
AB  - To determine whether serum supplementation influenced fatty acid content of
      bovine blastocysts and whether vitamin E addition to culture medium containing
      serum could improve development in vitro, cleaved eggs were cultured in synthetic
      oviduct fluid supplemented with bovine serum albumin (BSA, 0.4% w/v, fraction V)
      (SVBSA), fetal calf serum (FCS, 10% v/v) (SFCS) or FCS (10% v/v) plus 100 micro M
      vitamin E (SFCS + E). Blastocyst yields were recorded and fatty acid composition
      was determined by gas chromatography. Day 7 blastocysts were incubated with [2
      (14)C] pyruvate for 3 h and then fixed for cell counts. Yields of good quality
      blastocysts were greatest from cleaved eggs cultured in serum-free conditions (P
      < 0.01). In the presence of serum, supplementation with vitamin E increased both
      total and good quality blastocyst yields (P < 0.01). Presence of serum increased
      fatty acid content (mean +/- SEM) of blastocysts (SVBSA v. SFCS = 57 +/- 2 v. 74
      +/- 2 ng embryo(-1); P < 0.001). In contrast, pyruvate metabolism was greater in
      blastocysts produced without serum (27 +/- 3 v. 21 +/- 3 picomoles embryo(-1) 3h(
      1); P < 0.01) but, on a per cell basis, no differences were detected. Addition of
      vitamin E to the serum-supplemented formulation did not alter either the fatty
      acid content (73 +/- 2 ng embryo(-1)) or pyruvate metabolism index (19 +/- 1 pmol
      embryo(-1) 3h(-1)) of SFCS + E blastocysts. Thus, despite lipid accumulation,
      supplementary vitamin E improved blastocyst yields in embryos exposed to serum.

PMID- 14588187
TI  - Anatomy and chromosomes of two intersexual dasyurid marsupials.
AB  - The intersexual phenotypes of marsupials with XXY and XO chromosome constitutions
      imply that not all sexual dimorphisms are under the control of testicular
      hormones and, ultimately, the SRY gene on the Y chromosome. It has been
      hypothesised that there is a gene on the X chromosome that determines whether
      either a scrotum will form (one copy of the gene) or a pouch with teats (two
      copies of the gene). Here, we describe the anatomy and chromosomes of two
      intersexual dasyurid marsupials. One, a Dasyuroides byrnei, had a pouch, but the
      reproductive tract was essentially male. The other, a Sminthopsis douglasi, had a
      hemipouch and a hemiscrotum and the reproductive tract was essentially female.
      The S. douglasi was a mosaic for cells with an apparently normal 2n = 14, XX
      female karyotype and cells with 2n = 14 plus (usually) two dot-like supernumerary
      elements 2n = 14, XX + 2B. The D. byrnei cells examined also had a 2n = 14, XX +
      2B karyotype. In fibroblasts from the male and female sides of the S. douglasi,
      it was possible to assign the 2n = 14, XX karyotype to the male side and the 2n =
      14, XX + 2B to the female side.

PMID- 14588188
TI  - In vitro maturation of oocytes from non-stimulated common wombats.
AB  - Assisted reproductive techniques, such as in vitro oocyte maturation in
      conjunction with in vitro fertilisation, may be used as a tool to manipulate
      reproduction. Using the common wombat as a model for the critically endangered
      northern hairy-nosed wombat, the present study examined whether oocyte maturation
      could be achieved under field conditions. At the time of collection, no oocytes
      were at the metaphase II (MII) stage (0/42). After 60 h culture using the
      submarine incubation system, 34% of oocytes (24/70) matured to telophase/MII, as
      indicated by the presence of a polar body. The proportion of oocytes that reached
      MII was higher for oocytes collected from follicles >2 mm in diameter compared
      with follicles <2 mm (40% v. 22%, respectively). The presence of cumulus cells
      alone did not influence the maturation potential. Oocytes without cumulus cells
      collected from follicles >2 mm in diameter had the highest maturation rate (58%).
      Maturation was not affected by the reproductive status of the common wombat or a
      delay of up to 5 h before oocyte collection. In conclusion, the present study
      demonstrated that oocytes collected from non-stimulated common wombats can mature
      to MII in culture.

PMID- 14588189
TI  - [Thiopurine methyltransferase activity in patients with autoimmune hepatitis].
AB  - BACKGROUND AND OBJECTIVE: The measurement of the activity of thiopurine
      methyltransferase (TPMT) is useful to monitor, on an individual basis, the dose
      of azathioprine in order to identify patients at risk of myelotoxicity. However,
      the distribution of the enzymatic activity in patients with autoimmune hepatitis
      is unknown. Our objective was to analyze the activity of TPMT in a group of 200
      patients with autoimmune hepatitis and to evaluate the possible effect of some
      variables such as the treatment with azathioprine on this activity. PATIENTS AND
      METHOD: The activity of TPMT was determined by a radiochemical method; the
      activity was determined in the erythrocytes of patients with autoimmune hepatitis
      from 31 Spanish hospitals. We studied the relationship between TPMT levels and
      several demographic variables as well as its correlation with azathioprine
      treatment. RESULTS: We included 209 patients (80% females, mean age 50 years, 39%
      on azathioprine). The mean value of TPMT was 20.7 U/ml erythrocytes (from 0 to
      39). TPMT levels were adjusted to a normal distribution. 1%, 9% and 90% patients
      had low (< 5 U/ml), intermediate (5-13.7 U/ml) and high (>= 13.8 U/ml) TPMT
      levels, respectively. In the multivariate analysis, there were no differences
      when comparing the mean TPMT values according to age, gender or previous
      azathioprine treatment. CONCLUSIONS: TPMT activity in patients with autoimmune
      hepatitis displays a similar distribution to that reported in other populations
      (approximately 1% of patients have low levels and 9% have intermediate levels)
      and it does not depend on the age, gender or simultaneous azathioprine treatment.

PMID- 14588190
TI  - [Cardiovascular risk factors in overweight and obesity. Changes after a weight
      loss treatment].
AB  - BACKGROUND AND OBJECTIVE: For the treatment of obesity, an adecuate control of
      associated cardiovascular risk factors (CRF) is fundamental. The objective of
      this study was to assess the relationship between body mass index (BMI) and CRF,
      and the effect of a weight loss program on overweight subjects. PATIENTS AND
      METHOD: A single-centered cross-sectional prospective study was carried out
      during 1997-2001 on 1,018 overweight subjects (788 women and 230 men) who were
      seeking aid to lose weight at an obesity clinic. A program involving a
      hypocaloric, Mediterranean diet was prescribed plus recommendations for spare
      time exercise. Variables measured included weight, height, blood pressure, serum
      lipids and blood glucose concentrations, measured both at baseline and at the end
      of the weight loss program. RESULTS: After adjusting for age, variables showing a
      significant increase upon higher BMI were: blood pressure, HDL cholesterol (HDL
      C) (inverse relationship, only in women), triglycerides and blood glucose. Total
      cholesterol (CLT), LDL cholesterol (LDL-C) and CLT/HDL-C showed no relationship
      with BMI. Weight loss had beneficial effects on blood pressure and triglycerides,
      regardless of the initial values, and on CLT, LDL-C and CLT/HDL-C when the
      initial levels were increased. No significant changes were found with regard to
      HDL-C. CONCLUSIONS: Overweight and obese subjects carry a burden of common
      coronary risk factors which ncrease upon greater obesity. Weight loss has
      important beneficial effects with regard to coronary risk factors associated with
      overweight and obesity, particularly if these factors are previously altered,
      even when weight loss is < 5% of initial weight.

PMID- 14588191
TI  - [Analysis of six families with microepidemics detected in the tuberculosis
      contact tracing].
AB  - BACKGROUND AND OBJECTIVE: The aim of the present study was to analyze the
      characteristics of families with microepidemics of tuberculosis. PATIENTS AND
      METHOD: We included family studies examined in the Center for Tuberculosis
      Control and Prevention of Lleida during the period 1991-97. A microepidemic was
      defined as the appearance of two or more new cases in the same family study. The
      association between the detection of new cases among family contacts and the
      prevalence of tuberculosis infection was analyzed. RESULTS: Prevalence of
      families with microepidemics was 1.4% (6/437). Families with microepidemics
      generated 15 out of 39 newly diagnosed cases (38.5%). We observed a higher
      prevalence of tuberculosis infection in families with one new case (OR = 1.67; CI
      95%, 1.19-2.34) and in families with microepidemics (OR = 2.67; CI 95%, 1.28
      5.62). CONCLUSIONS: Study of microepidemics of tuberculosis is very important
      because a small percentage of families with microepidemics (1.4%) generate a
      large number of secondary cases who are diagnosed during the screening of
      tuberculosis contacts (38.5%).

PMID- 14588192
TI  - [Study of contacts in the XXI Century: innovations are needed].

PMID- 14588193
TI  - [Weight loss in a patient with morbid obesity under treatment with oleoyl
      estrone].
AB  - BACKGROUND AND OBJECTIVE: Oleoyl-estrone administration in rats results in loss
      of body fat and sparing protein via decreasing food intake and maintaining energy
      expenditure. Oleoyl-estrone also decreases insulin resistance and hyperlipidemia
      and has no direct estrogenic effects. Our objective was to determine whether oral
      oleoyl-estrone was effective in the treatment of morbid obesity in a voluntary
      patient. PATIENT AND METHOD: Oleoyl-estrone (150-300 mol/d) was given to a morbid
      obese man (BMI: 51.9) over 10 consecutive 21-day trial periods of oral drug
      intake followed by at least two months of recovery. This treatment was given
      without additional dietary restrictions. Plasma metabolites, hormones and enzymes
      were measured before treatment, during active administration and at recovery
      periods. RESULTS: Oleoyl-estrone decreased the body weight (38.5 kg in 27 months,
      final BMI: 40.5). No rebound trends were observed. No significant changes in
      blood parameters, plasma metabolites, hormones or enzymes were observed as a
      consequence of the treatment. CONCLUSIONS: Oleoyl-estrone decreased body weight
      in this subject without affecting metabolites or hormones, similarly to its
      effects in animal models. This means that oleoyl-estrone could have a marked
      potential as an anti-obesity drug.

PMID- 14588194
TI  - [Alternative drugs for obesity treatment: myth and reality].

PMID- 14588196
TI  - [Acute demyelinating polyradiculopathy Miller-Fisher variant associated with
      Salmonella gastroenteric infection].

PMID- 14588195
TI  - [Neurotoxins with anticholinesterase activity and their possible use as warfare
      agents].
AB  - Anatoxin-a(s), onchidal and fasciculins are neurotoxins with anticholinesterase
      activity. An intoxication by these neurotoxins is characterized by cholinergic
      syndromes similar to organophosphate insecticide and nerve agent intoxications.
      Anticholinesterase neurotoxins, as well as other toxins, have some disadvantages
      if used as weapons of mass destruction. Drawbacks include difficulties to produce
      them in big quantities and their dissemination in form of aerosols. However,
      other properties such as high toxicity, improbable identification with common
      commercial portable detectors for chemical warfare agents and toxic industrial
      chemicals, as well as the lack of effectiveness of antidotal treatments with
      oximes may make them attractive in order to be used in military operations or
      terrorist attacks. For these reasons, it should be necessary to control these
      neurotoxins through international treaties which have real verification measures
      such as the Chemical Weapons Convention.

PMID- 14588197
TI  - [Cranial inflammatory pseudotumor and giant cell arteritis].

PMID- 14588198
TI  - [Delayed myelopathy in hight tension electric-burn].

PMID- 14588199
TI  - [The role of the pulmonologist in chemotherapy for lung cancer].

PMID- 14588201
TI  - [Lung cancer mortality in Andalucia, 1975-2000].
AB  - OBJECTIVE: To describe trends in lung cancer mortality in Andalucia, Spain,
      during the period from 1975 through 2000. SUBJECTS AND METHOD: Records of lung
      cancer deaths for the period from 1975 through 2000 were obtained from the
      Statistical Institute of Andalucia. The following indicators were calculated:
      crude rates, age-adjusted rates, truncated rates, and cumulative rates. RESULTS:
      Mortality rates for men dropped in all subject groups aged over 50 years during
      the period from 1994 through 2000. In women mortality rates were much lower,
      although we observed an increase in the 35-39 and 45-49 age groups, which is
      reflected in the 6.1% rise in the truncated rates (35-64 years) during the period
      from 1994 through 2000. In older women mortality rates fluctuated more within the
      different age groups, although on the whole the truncated rate for all those over
      65 years old fell by 9.7% in the period between 1995 and 2000. CONCLUSION: Lung
      cancer mortality rates among men in Andalusia began to decrease after 1994. In
      contrast, mortality increased among young women, although their rates are still
      very low.

PMID- 14588200
TI  - [Description of a sample of patients with chronic obstructive pulmonary disease
      treated at hospital-supervised respiratory clinics at primary care centers].
AB  - OBJECTIVE: To study the general characteristics, health perception and
      limitations of patients with chronic obstructive pulmonary disease (COPD) treated
      at respiratory clinics at primary care centers staffed by pulmonologists from our
      hospital service. METHOD: The study was carried out at 5 primary care centers
      that enrolled the patients consecutively. Questionnaires were used to collect
      information on sociodemographic aspects, perception of health, and limitations to
      activities of daily living. We also collected information on the treatments
      patients were receiving and comorbidities. Spirometry was also performed.
      RESULTS: Six hundred eleven patients with a mean age of 67.2 years were included
      in the study; 97.7% were male. The most common comorbidities were spinal column
      pathology (43%) and osteoarthritis (37%). The mean forced expiratory volume in 1
      second (FEV1) was 1.37 L and FEV1% was 49.7% of predicted. Medications taken for
      COPD were mainly beta-adrenergics and anticholinergics; 66% of patients used
      inhaled steroids. The majority of patients (52.7%) referred to their health as
      fair and 59.9% declared having some degree of limitation to their activities of
      daily living which they attributed to their respiratory disease. Statistical
      differences were found between the degree of limitation and the degree of dyspnea
      (P<.0001), perception of health (P<.0001), and FEV1 (P=.001). CONCLUSIONS: Our
      study outlines the general characteristics of COPD patients and shows that
      dyspnea is closely related to the perception patients have of their degree of
      limitation.

PMID- 14588202
TI  - [Transbronchial needle aspiration in bronchogenic carcinoma with visible lesions:
      diagnostic yield and cost].
AB  - BACKGROUND: Transbronchial needle aspiration (TBNA) is a bronchoscopic technique
      whose usefulness in diagnosing endobronchial lesions has not yet been clearly
      established. OBJECTIVE: We aimed to determine whether the diagnostic yield of
      fiberoptic bronchoscopy could be increased, without a negative impact on
      diagnostic costs, if TBNA were used in combination with conventional diagnostic
      techniques (bronchial washings and bronchial brushings and forceps biopsy).
      PATIENTS AND METHODS: The cases of 130 patients diagnosed with bronchogenic
      carcinoma with endoscopically visible lesions were analyzed retrospectively. All
      had undergone conventional diagnostic procedures; TBNA was also performed if the
      bronchoscopist considered it was indicated. The final cost was calculated in
      euros for each diagnosis as the sum of the cost of the procedures needed to reach
      the diagnosis, including both endoscopic procedures and others (transthoracic
      needle aspiration, lymph node biopsy). Diagnostic yield and costs in cases
      diagnosed using only conventional techniques were compared to the yield and costs
      in cases in which both conventional techniques and TBNA were used. RESULTS: TBNA
      was performed in 49 patients and provided the diagnosis in 85.7%. Conventional
      techniques led to cytological and histological diagnosis in 80.2% of the cases,
      and the combination of conventional techniques and TBNA gave a diagnosis in 89.7%
      (P=.01). Significant differences were observed in extrinsic compression
      (conventional 37.5%; conventional+TBNA 100%; P=.01), submucosal infiltration
      (conventional 54.6%; conventional+TBNA 85%; P=.03), and exophytic mass with
      necrosis (conventional 80%; conventional+TBNA 100%; P=.01). The mean (SD) cost of
      diagnosis was euros 381.60 (euros 156.53) using conventional techniques and euros
      413.25 (euros 112.91) for conventional techniques in combination with TBNA. By
      adding TBNA, costs decreased for diagnoses of submucosal infiltration, exophytic
      mass with necrosis and extrinsic compression, although the saving was significant
      only for extrinsic compression. CONCLUSION: The diagnostic yield of TBNA is high
      for endoscopically visible bronchial anomalies suggesting neoplasm, particularly
      when the lesion is due to extrinsic compression, submucosal infiltration, or
      exophytic mass with necrosis.

PMID- 14588203
TI  - [Factors associated with complications caused by bronchoscopy in pediatric
      patients].
AB  - BACKGROUND: Although the role of flexible bronchoscopy as an important diagnostic
      and therapeutic tool in pediatric medicine has been demonstrated, the procedure
      can cause complications which should be foreseen by the bronchoscopist. However,
      no precise information is available about the factors associated with the
      presence of such complications. OBJECTIVE: To determine the incidence of
      complications caused by bronchoscopy in pediatric patients and the factors
      associated with their presence. MATERIAL AND METHOD: This was a retrospective
      cohort study which reviewed the records of patients aged between 1 month and 18
      years who had undergone bronchoscopy between January 1 and December 31, 2002. The
      presence or absence of several variables considered predictive of
      postbronchoscopy complications was recorded in each patient. RESULTS: After
      adjustment for the method used to access the airway, age less than or equal to 3
      months was the only independent factor associated with the presence of
      complications (odds ratio = 8.19; 95% confidence interval, 1.61-41.55; P=.01).
      CONCLUSIONS: We conclude that patients 3 months old or younger are at greater
      risk of presenting complications after bronchoscopies performed under general
      anesthesia. Consequently a risk-benefit analysis should be carried out for
      patients in this age group, and the possibility of performing the procedure under
      sedation should be considered.

PMID- 14588204
TI  - [New approaches to the surgical treatment of severe thoracic cage diseases with
      respiratory repercussions].

PMID- 14588205
TI  - [Recommendations on the treatment of tobacco dependence].

PMID- 14588206
TI  - [Bronchial nodules produced by Strongyloides stercoralis as the cause of
      bronchial obstruction].
AB  - Infection by Strongyloides stercoralis can cause asthma-like symptoms through
      mechanisms that have not yet been clarified. A 55-year-old male farm worker with
      a 2-year history of illness diagnosed as asthma and treated unsuccessfully with
      bronchodilators and corticosteroids was referred to our hospital with severe
      dyspnea. The initial chest radiograph showed mild air trapping, and pulmonary
      function tests detected airway obstruction that did not respond to salbutamol.
      Bronchoscopy revealed multiple nodules protruding into the airway lumen. S.
      stercoralis larvae were detected in bronchoalveolar lavage fluid and stool
      samples. Although treatment with albendazole was initiated, the patient's
      condition worsened over the next 3 days, hemoptysis presented, and the process
      ended in death. Autopsy demonstrated Strongyloides larvae in the bronchial
      nodules. Infection by S. stercoralis should be considered in the differential
      diagnosis of asthmatic-like symptoms refractory to treatment. In such cases
      nodules may be responsible for obstruction.

PMID- 14588207
TI  - [Intraparenchymal pulmonary inflammatory pseudotumors].
AB  - Inflammatory pseudotumors are rare entities which occasionally affect the
      pulmonary parenchyma. Their clinical diagnosis arises in a variety of ways and
      half the time they are detected by chance. Deciding on a therapeutic approach is
      difficult because a firm diagnosis is established only after studying the excised
      tissue. We describe our experience with the diagnosis, surgical treatment, and
      follow up of 4 cases of inflammatory pseudotumor located in the pulmonary
      parenchyma and treated by surgical resection (by thoracotomy or video assisted
      thoracoscopic surgery) with good outcomes following complete resection.

PMID- 14588208
TI  - [Type I neuroendocrine pulmonary tumor: local recurrence with mediastinal
      involvement].

PMID- 14588209
TI  - [Thoracic retraction after chemical pleurodesis by video-assisted thoracoscopy
      for spontaneous juvenile pneumothorax].

PMID- 14588210
TI  - [Pulmonary embolism caused by a barium enema].

PMID- 14588211
TI  - [On nurses' understanding of tuberculin testing: the importance of training].

PMID- 14588212
TI  - [Return of Haemophilus influenzae type b infection?].

PMID- 14588213
TI  - [Antibody titer, immunological memory, or both?].

PMID- 14588214
TI  - [FMRP immunodetection on hair roots: application to the diagnosis of fragile X
      syndrome].
AB  - INTRODUCTION: Fragile X syndrome is the most common inherited form of mental
      retardation. The absence of FMRP protein, codified by the FMR1 gene, results in
      fragile X phenotype. DNA-based diagnostic methods determine the length of the CGG
      repeat within the FMR1 gene, the main mutation causing the syndrome.
      Immunohistochemical diagnostic tests detect all mutations leading to the absence
      of FMRP expression. Results of the antibody test on hair roots correlate with
      intellectual quotient in affected men and women. PATIENTS AND METHODS:
      Immunohistochemical techniques were used to study FMRP expression in hair roots
      in a control group to establish the correlation with the length of the CGG
      repeat. Subsequently, 65 girls and boys with mental retardation attending special
      schools were screened by using the FMRP test on hair roots. RESULTS: Males and
      females molecularly characterized as within the normal and premutated range
      expressed FMRP in more than 70 % of hair roots. Full mutation carriers expressed
      FMRP in less than 70 % of hair roots. Immunohistochemical studies in males and
      females with mental retardation led to the identification of one affected male.
      CONCLUSIONS: Fragile X syndrome detection by immunohistochemical testing of hair
      roots is a valid method of population screening because of the relative
      noninvasiveness of obtaining samples, and the ease and rapidness of the
      technique, which can be applied to routine clinical practice.

PMID- 14588215
TI  - [Estimation of creatinine clearance by the height/plasma creatinine formula in
      critically-ill children].
AB  - INTRODUCTION: Critically-ill children frequently show impaired renal function,
      necessitating adjustment of drug dosages. Our objectives were to study estimated
      creatinine clearance through the correlation between the height/plasma creatinine
      formula (CrClest) and measured creatinine clearance (CrClms) and to examine
      whether CrClest over- or underestimates CrClms by analyzing the influence of
      diagnosis, severity, and the practical consequences. PATIENTS AND METHODS:
      Seventy-seven patients admitted to the pediatric intensive care unit were
      included. CrClms was calculated using serum creatinine and creatinine in urine
      collected over 24 hours. CrClest was estimated using serum creatinine, height,
      and a constant. The difference between CrClms and CrClest was expressed as a
      percentage: (CrClms CrClest) x 100/CrClms. Differences of greater than 15 % were
      considered poor estimates. ResultsThe mean percentage difference was 29.2
      (standard error: 39.9). There were no differences among diagnoses in the
      distribution of significant bias, although the frequency of metabolic diagnoses
      was high. Incorrect evaluation of CrClest would result in a therapeutic error in
      11.69 % of the cases, with overdosage in 10.39 %. The Pediatric Risk of Mortality
      (PRISM) score was higher (p < 0.05) in patients at risk for overdosage.
      CONCLUSIONS: CrClest estimation using the height/plasma creatinine formula was
      not an accurate method in critically ill children. In 10.39 % of patients with
      more severe illness, the dosage of renally excreted drugs would be too high. The
      highest risk was found in patients with metabolic and neurological diagnoses.

PMID- 14588217
TI  - [Childhood circumcision: review of the evidence].
AB  - Circumcision is one of the most frequent surgical procedures in children. Because
      of greater immigration to Spain, health professionals need to know how to
      interpret new health demands. One of the most important of these is ritual
      circumcision. Moreover, in the last few years scientific data showing the
      potential health benefits of circumcision have been published. The aim of this
      study was to identify the therapeutic indications of this procedure, to clarify
      the origins of its cultural and religious bases and, finally, to review the
      scientific evidence to date on its possible benefits.

PMID- 14588216
TI  - [Convulsive syncope: characteristics and reproducibility using the tilt test].
AB  - OBJECTIVES: To establish the main clinical characteristics of convulsive syncope
      and the usefulness of the tilt test in its diagnosis. METHODS: A total of 317
      patients (aged 5-18 years old) under clinical suspicion of neurocardiogenic
      syncope underwent a multiparametric tilt test. Our tilt test protocol includes
      continuous noninvasive measurement of heart rate, blood pressure, and arterial
      oxygen saturation, as well as continuous noninvasive measurement of cerebral
      oxygen saturation by near-infrared spectrophotometry. In selected patients,
      simultaneous electroencephalogram (EEG) was performed. RESULTS: The tilt test was
      positive in 216 patients (68.1 %). Of these, 25 (11.6 %) showed seizures during
      the test (convulsive syncope). Convulsions were asymmetric-tonic in 15 patients
      (60 %), generalized tonic in 5 (20 %), and tonic-clonic in 5 (20 %). In all
      patients, convulsive episodes lasted less than 30 seconds and spontaneously
      ceased upon placing the patient in a horizontal or Trendelenburg position. When
      simultaneous EEG was performed, diffuse brain wave slowing was observed, without
      paroxysmal activity. CONCLUSIONS: Convulsive syncope is not an uncommon event in
      children and is easily elicited by means of the tilt test. Pediatricians should
      be aware of this finding in order to avoid the frequently established
      unidirectional association between seizures and epileptic disorders.
      Consequently, the tilt test should be considered an essential tool in the
      differential diagnosis between convulsive syncope and epilepsy.

PMID- 14588218
TI  - [Neurological follow-up of very low birth weight newborns at the age of two years
      (1998-1999)].
AB  - BACKGROUND: Because of improved obstetric and neonatal care, there is growing
      interest in the later outcome of very low birth weight newborns. OBJECTIVES: The
      aim of this study was to evaluate the survival rate of very low birth weight
      newborns and to identify disabilities at the age of 2 years. MATERIAL AND
      METHODS: An observational, follow-up study was performed of neonates with a birth
      weight of under 1,500 grams born between 1998 and 1999. The follow-up program
      included pediatric, maturative, neurological, psychological, ophthalmological,
      and audiological evaluation. Neurosensorial disabilities were classified as mild,
      moderate, or severe. RESULTS: One hundred thirty-six very low birth weight
      newborns were admitted. The survival rate was 77.9 % and 83.9 % completed the
      follow-up to the age of 2 years. The neurosensorial disability rate was 20.2 %;
      disability was severe in 9 %, moderate in 1.1 %, and mild in 10.1 %. In patients
      lost to follow-up, birth weight was higher, gestational age was older, and
      sonographic findings were more frequently normal. CONCLUSION: Survival in very
      low birth weight newborns has increased with improved neonatal care. The presence
      of sequelae was similar to that found in other follow-up studies. A substantial
      number of patients were lost to follow up, which influenced the disability rates.

PMID- 14588220
TI  - [Treatment of septic shock with continuous plasmafiltration and
      hemodiafiltration].
AB  - Despite recent therapeutic advances, mortality due to septic shock remains high.
      The most important causes of mortality are refractory shock, uncontrollable
      alterations of coagulation, and multiorgan failure. Some authors have proposed
      the early use of plasmafiltration and high flow hemodiafiltration for refractory
      septic shock. Most authors initiate treatment with a short session of
      plasmafiltration followed by continuous hemodiafiltration. A 13-year-old girl
      presented refractory meningococcal septic shock, disseminated intravascular
      coagulation, and acute renal failure unresponsive to volume expansion and high
      doses of adrenalin and noradrenaline. She received simultaneous treatment with
      plasmafiltration and continuous venovenous hemodiafiltration for 30 hours. Two
      pumps of extrarenal purification placed in parallel through the same double line
      catheter were used. Fast hemodynamic stabilization and control of the
      coagulopathy were achieved. The patient survived with progressive recovery of
      renal function but required amputation of the inferior left limb. Continuous
      plasmafiltration and venovenous hemodiafiltration can be used simultaneously for
      the treatment of older children with septic shock, severe coagulopathy, and
      hypervolemia.

PMID- 14588219
TI  - [Techniques and complementary techniques. Intubation, sedation and adaptation to
      mechanical ventilation].
AB  - Endotracheal intubation consists on placing a tube in the trachea either through
      the mouth (orotracheal intubation) or through the nose (nasotracheal intubation).
      Although maintaining the airway patent and providing adequate ventilation are not
      synonymous with intubation, this procedure provides a closed ventilation system
      while ensuring patency and protecting the airway. Intubation is fairly safe in
      oxygenated and physiologically stable patients but it is not free from serious
      complication and consequently it should always be considered as a dangerous
      technique, especially in critically-ill patients. In addition, given that the
      anatomy of the airway in children differs according to age, the techniques used
      to intubate show considerable variations. For all these reasons and despite the
      often urgent nature of airway problems in children, the placement of an
      endotracheal tube must be approached in a deliberate and calm manner if trauma to
      the airway and patient instability are to be avoided. Thus, whenever
      circumstances permit, intubation should be carefully prepared with assessment of
      factors that might cause problems such as the indication for intubation, possible
      airway abnormalities, risk of aspiration, and hemodynamic, respiratory and
      neurological status. Such and evaluation allows the most appropriate intubation
      technique to be chosen.

PMID- 14588221
TI  - [Criss-cross heart with atrioventricular discordance, straddling A-V valve,
      double outlet right ventricle and preexcitation].
AB  - We report the case of a newborn with cyanosis, dyspnea, and supraventricular
      tachycardia due to reentry with good response to medical therapy. The diagnosis
      was made by echocardiography. The patient died suddenly at 6 days of follow-up.
      Necropsy confirmed the following anomaly: criss-cross heart with straddling right
      atrioventricular valve, and left atrioventricular valve stenosis connected to the
      anterior trabeculated ventricle giving rise to the pulmonary artery and
      aorta.Precocious rotation when septal closure is not concluded favors
      atrioventricular valve anomalies and rhythm disorders.

PMID- 14588222
TI  - [Blood lead levels in children from a neighborhood in Barcelona].

PMID- 14588223
TI  - [Beta-thalassemia minor and seronegative oligoarthritis].

PMID- 14588224
TI  - [Learning to manage sickle cell anemia].

PMID- 14588225
TI  - [Neurocysticercosis: an imported cause of acquired epilepsy].

PMID- 14588226
TI  - [Acral purpuric lesions and fever].

PMID- 14588227
TI  - [1st National Congress of Pediatric Cardiology (I). Sevilla, Spain, 23-24 May
      2003. Abstracts].

PMID- 14588229
TI  - [Bone scintigraphy and somatostatin receptor scintigraphy in pediatric patients
      with bone involvement in Langerhans cell histiocytosis].
AB  - Langerhans cell histiocytosis (LCH) is a granulomatous disease which can involve
      multiples sites of the body. Diagnostic imaging is of utmost importance in the
      management of these patients. Up to now radiographic skeletal survey and bone
      scintigraphy (BS) have been used to assess bone involvement (both with low
      specificity). Magnetic resonance imaging (MRI) and CT have been used to assess
      visceral involvement but with the limitation that they cannot give information
      about the functional status. Recently somatostatin receptor scintigraphy (SSRS)
      has been proposed to detect active lesions and to monitor response to treatment.
      The aim of this study is to assess bone and somatostatin receptor scintigraphy in
      the detection of bone involvement in LCH in children. Twenty scintigraphies (12
      SSRS and 8 BS) were performed in seven patients (3 girls and 4 boys) aged at
      diagnosis: 18 month-12 years (mean age 6 years). The findings obtained in the
      scintigraphies were compared with clinical evolution and other imaging
      techniques. Bone scintigraphy detected all the LCH bone lesions, and discovered
      one unknown lesion. SSRS scintigraphy visualised the active lesions in 3 patients
      (clinical and other imaging techniques were also positive). SSRS was negative in
      one patient classified as disease free and another in clinical remission. SSRS
      detected 2 new unknown bone lesions, but could not detect LCH bone lesions
      confirmed in other imaging techniques in 2 patients. Somatostatin receptor and
      Bone scintigraphy can be used to detect active LCH bone lesions in children and
      can help to monitor response to treatment. Further studies with more patients are
      needed to confirm the diagnostic usefulness of these techniques.

PMID- 14588230
TI  - [Neuroactivation of the Tower of Hanoi in patients with obsessive-compulsive
      disorder and healthy volunteers].
AB  - The aim of the study was to evaluate changes in regional cerebral blood flow
      (rCBF) in obsessive-compulsive disorder (OCD) patients and healthy controls
      during performance of Tower of Hanoi (TOH) test (cognitive task). MATERIAL AND
      METHODS: We compared TOH test performance in 30 OCD patients and 30 individually
      matched healthy volunteers. Intelligence and anxiety measurements were taken into
      account for all participants. Within the patient group, factors such as duration
      and severity of symptoms and low mood were considered. rCBF was estimated through
      the uptake of 99mTc-hexamethylpropylamine-oxime (HMPAO) on single photon emission
      computerised tomography (SPECT). Regional values were quantified as ratios of
      cortical blood flow. RESULTS: OCD patients and volunteers differed significantly
      in terms of subjective anxiety during procedures. TOH test performance was
      significantly impaired in OCD patients when compared with matched controls. 2
      tailed t tests for repeated measures suggested that there were overall
      significant differences (p = 0.039) between both groups (OCD patients and
      controls) confined to left caudate activation. There was increased activity after
      activation in control subjects, but not in OCD patients. No differences in other
      regions were observed. CONCLUSIONS: These results suggest a modification of the
      activating systems of basal ganglia functions in OCD compared with normal
      subjects.

PMID- 14588231
TI  - [Clinical significance of tumor content of epidermal growth factor receptor in
      breast cancer].
AB  - OBJECTIVE: To determine the content of epidermal growth factor receptor (EGFR)
      using a radioligand method in breast cancer and to analyze the relationship
      between the EGFR levels and the characteristics of patients and tumors.
      Prognostic significance was also analyzed. MATERIAL AND METHODS: EGFR was
      measured by a single point radioligand assay in 265 invasive breast carcinomas
      tissues. In addition, estrogen and progesterone receptors (ER and PR) were
      measured by enzymatic immunoassays. We analyze the relationship of EGFR levels
      with the different clinico-pathologic parameters. RESULTS: EGFR levels in breast
      carcinomas varied widely (0.1 to 403) with a median at 4 fmol/mg prot. The
      significantly higher concentrations of EGFR were detected in patients under 60
      years old (p = 0.042), undifferentiated tumors (p = 0.04), and carcinomas with
      negative ER and PR (p < 0.019 y p < 0018, respectively). In addition, there was a
      negative correlation between EGFR and the ER and PR levels (p < 0.05). EGFR
      levels did not show any relationship with the patient's prognosis. CONCLUSIONS:
      In addition, intratumoral levels of EGFR in breast carcinomas vary widely and the
      highest concentrations are associated with the most aggresive characteristics of
      the tumor.

PMID- 14588232
TI  - [Incidence of pulmonary scintigraphic changes in women irradiated for breast
      cancer].
AB  - OBJECTIVE: To determine the incidence of respiratory function changes on
      quantified ventilation-perfusion scintigraphy produced by breast cancer radiation
      therapy and its correlation with irradiated lung volume. MATERIAL AND METHODS:
      Prospective study on 43 patients with breast cancer who received adjuvant
      radiotherapy. Quantified ventilation-perfusion scintigraphy was carried out
      before and after radiotherapy (3 and 9 months). The differences of ventilation
      and perfusion were calculated subtracting the irradiated lung values from the
      contralateral lung values, and their correlations with the irradiated lung volume
      were analyzed. RESULTS: The scintigraphic parameter means of the irradiated lung
      were significantly lower than those of the contralateral lung, after
      radiotherapy. The incidence of patients with a total perfusion and ventilation
      decrease over 10 % was 21 %, except for the three-month ventilation, which was 23
      %. The total ventilation difference was significantly correlated with the lung
      volume, presenting decreases over 10 % for volumes of 100 cm3 or more. All
      patients remained asymptomatic. CONCLUSIONS: The pulmonary scintigraphy changes
      derived from the breast cancer radiotherapy produced no clinical symptomatology.
      Regarding scintigraphy, ventilation decreases when the irradiated lung volume
      increases, so a follow-up of these patients' pulmonary function should be
      performed when the lung volume irradiation cannot be lower than 100 cm3.

PMID- 14588233
TI  - [99m-Tc sestamibi scintigraphy in primary hyperparathyroidism. Importance of
      lateral projections using a pin-hole collimator].
AB  - 99mTc-Sestamibi double-phase scintigraphy has been improved with digital and
      tomographic procedures as well as additional projections. Since two years ago, we
      have introduced additional early lateral views of neck to the conventional double
      phase scintigraphy. We have tried to give anatomic data about the depth of the
      adenomas and to evaluate the possibility of obviating the late images of the
      double-phase study. METHOD: Two observers reviewed 50 studies performed for
      primary hyperparathyroidism in two different ways. The first one reviewed only
      conventional double-phase studies and the second one, with the additional report
      of the lateral views. RESULTS: in 32/50 patients (64 %) the report of the
      additional lateral views and the conventional early views was enough to diagnose
      parathyroid adenomas. No additional lesions were observed in the late views.
      These views did not provide any additional useful data and could have been
      obviated. Four ectopic adenomas were found, 1 mediastinal and 3 in paraesophagic
      area; three intrathyroidal focus; all of these atypical lesions were identified
      by lateral pinhole views. CONCLUSION: The performance of additional lateral
      projections of the parathyroids supplies additional information to the surgeon on
      the depth of the lesion in atypical sites and would have made it possible to
      obviate the late phase in more than half of the patients since this did not
      supply additional information to that of the early images that had reached a
      diagnosis.

PMID- 14588234
TI  - [Preoperative lymphoscintigraphy to identify the sentinel lymph node in breast
      cancer].
AB  - INTRODUCTION: The preoperative lymphoscintigraphy to the Sentinel Node Biopsy
      (SNB) can reproduce the lymphatic drainage of the tumour in breast cancer.
      OBJECTIVES: To establish the pattern of lymphatic drainage of the mammary tumors
      by means of isotopic lymphoscintigraphy and determine the factors that could
      influence the negativity of the scintigraphy. METHODS: 121 patients with breast
      cancer who were going to undergo mammary surgery were studied with SNB. One day
      before the operation, 37 MBq 99mTc-colloidal sulphide colloid in a volume of 2 ml
      was injected in peritumoral tissue. Mammary lymphoscintigraphies were performed
      at 30 minutes and 18 hours P.I., in ANT and OA projections of the corresponding
      chest. After, the clinical-biological parameters and their influence on the
      result of the lymphoscintigraphy were analyzed. RESULTS: The scintigraphy were
      positive in 85 % of the patients. The axillary chain was observed in 97 % and the
      internal mammary chain in 11 %. The factors associated to the absence of
      visualization of the sentinel node were: older than 50 years (94 %), menopause
      (89 %), tumoral size > or = 2 cm (67 %), axillary metastases (67 %), the
      overexpression of C-erbB-2 oncoprotein (44 %) and proliferative activity > 10 %
      (67 %). CONCLUSIONS: The peritumoral injection of the radiocolloid establishes
      the lymphatic drainage pattern in the patients with breast cancer. Its absence of
      visualization can be associated to circumstances like: age > or = 50 years,
      menopause, tumoral size > or = 2 cm, axillary metastases, tumoral overexpression
      of the C-erbB-2 oncoprotein and high proliferative activity of the mammary tumor.

PMID- 14588235
TI  - [Positron emission tomography in a patient with Von Recklinghausen disease and
      left dorsal neurofibrosarcoma].
AB  - The development of neurofibrosarcomas in patients with Von Recklinghausen disease
      is a rare complication that can appear in the daily clinical practice. We report
      a clinical case with Von Recklinghausen disease and recurrence of a left dorsal
      neurofibrosarcoma diagnosed by Positron Emission Tomography with fluorine-18
      fluoro-deoxyD-glucose (FDG-PET). We believe this work is important due to the
      relatively uncommon clinical presentation and the discussion on the utility of 18
      FDG PET and other conventional imaging methods in the diagnosis of this entity.

PMID- 14588236
TI  - [Osteitis in secondary syphilis].
AB  - BACKGROUND: The aim of this study is to report two patients with osteitis in
      secondary syphilis. The increase in the number of cases of syphilis, linked to
      the changes in sexual behavior and to the increase of immigrants from areas of
      high prevalence of STD, as well as its relationship with HIV infection, makes
      important to clinicians become aware of unusual presentation of secondary
      syphilis. PATIENTS: We report two patients diagnosed of secondary syphilis, one
      of them with HIV infection. Both showed dermatological lesions in palms and
      soles, malaise and fever. Bone scintigraphy showed significant uptake in parietal
      and frontal bones in both patients. Clinical response was quickly achieved after
      penicillin treatment. CONCLUSIONS: In patients with secondary syphilis and
      osteoarticular symptoms luetic osteitis must be included in differential
      diagnosis. Bone scintigraphy should be the first diagnostic tool because it
      possibilities to perform a total body scan which allows localizing asymptomatic
      lesions. Moreover bone scan shows a high sensitivity.

PMID- 14588237
TI  - [99mTc-HDP lung uptake in metastatic pulmonary calcifications secondary to
      postoperative hypoparathyroidism].

PMID- 14588238
TI  - [Palliative treatment of metastasic bone pain].

PMID- 14588240
TI  - Trafficking through Rab11 endosomes is required for cellularization during
      Drosophila embryogenesis.
AB  - BACKGROUND: Embryonic cleavage leads to the formation of an epithelial layer
      during development. In Drosophila, the process is specialized and called
      cellularization. The trafficking pathways that underlie this process and that are
      responsible for the mobilization of membrane pools, however, remain poorly
      understood. RESULTS: We provide functional evidence for the role of endocytic
      trafficking through Rab11 endosomes in remobilizing vesicular membrane pools to
      ensure lateral membrane growth. Part of the membrane stems from endocytosed
      apical material. Mutants in the endocytic regulators rab5 and shibire/dynamin
      inhibit basal-lateral membrane growth, and apical endocytosis is blocked in
      shibire mutants. In addition, shibire controls vesicular trafficking through
      Rab11-positive endosomes. In shibire mutants, the transmembrane protein
      Neurotactin follows the secretory pathway normally but is not properly inserted
      in the plasma membrane and accumulates instead in Rab11 subapical endosomes.
      Consistent with a direct role of shibire in vesicular trafficking through Rab11
      endosomes, Shibire is enriched in this compartment. Moreover, we show by electron
      microscopy the large accumulation of intracellular coated pits on subapical
      endocytic structures in shibire mutants. Finally, we show that Rab11 is essential
      for membrane growth and invagination during cellularization. CONCLUSION:
      Together, the data show that endocytic trafficking is required for basal-lateral
      membrane growth during cellularization. We identify Rab11 endosomes as key
      trafficking intermediates that control vesicle exocytosis and membrane growth
      during cellularization. This pathway may be required in other morphogenetic
      processes characterized by the growth of a membrane domain.

PMID- 14588239
TI  - Switching between microtubule- and actin-based transport systems in melanophores
      is controlled by cAMP levels.
AB  - BACKGROUND: Intracellular transport involves the movement of organelles along
      microtubules (MTs) or actin filaments (AFs) by means of opposite-polarity MT
      motors or actin-dependent motors of the myosin family. The correct delivery of
      organelles to their different destinations involves a precise coordination of the
      two transport systems. Such coordination could occur through regulation of the
      densities of the two cytoskeletal systems or through regulation of the activities
      of the cytoskeletal motors by signaling mechanisms. RESULTS: To investigate the
      mechanisms of switching between MT and AF-dependent transport, we examine the
      influence of the densities of the MT and AF network on pigment transport in fish
      melanophores. We also change signaling by using activators and inhibitors of
      Protein Kinase A (PKA). We find that the key parameters characterizing pigment
      granule transport along MTs do not depend on MT density and are not significantly
      altered by complete disruption of AFs. In contrast, the kinetics of changes in
      these parameters correlate with the kinetics of changes in the intracellular
      levels of cAMP and are affected by the inhibitors of PKA, suggesting the
      regulation of MT- and AF-dependent motors by cAMP-induced signaling. Furthermore,
      perturbation of cAMP levels prevents the transfer of pigment granules from MTs
      onto AFs. CONCLUSIONS: We conclude that the switching of pigment granules between
      the two major cytoskeletal systems is independent of the densities of MT or AF
      but is tightly controlled by signaling events.

PMID- 14588241
TI  - The B cell SH2/PH domain-containing adaptor Bam32/DAPP1 is required for T cell
      independent II antigen responses.
AB  - BACKGROUND: Bam32/DAPP1 is a B cell adaptor composed of both a PH and an SH2
      domain. Previous studies in cell culture and chicken DT40 cells have indicated
      that Bam32 is critical for normal signaling downstream of the B cell receptor
      (BCR). RESULTS: We now study the function of Bam32 in mice in which Bam32 has
      been disrupted by a viral gene trap approach. Although B and T cell development
      is normal in Bam32(-/-) mice, B cell proliferation is reduced by about 50% after
      BCR crosslinking when compared with Bam32(+/+) mice. Differences in the
      activation of Erk, Jnk and p38 Map kinases, PLCgamma, and Ca(2+) flux do not
      account for the defect in proliferation as activation was similar in Bam32(+/+)
      and Bam32(-/-) B cells. Interestingly, whereas antibody response to T-dependent
      (TD) and T-independent (TI)-I antigens was similar between Bam32(+/+) and Bam32(
      /-) mice, TI-II responses were defective in Bam32(-/-) mice; Bam32(-/-) mice
      failed to undergo isotype class switch recombination (CSR) to produce IgG3
      antibodies due to a cell-autonomous defect in generation of IgG3 germline
      transcripts. The defect in TI-II antigen response led to an impaired antibody
      response to immunization with type 3 Streptococcus pneumoniae capsular
      polyschaccharide (PS), resulting in a markedly increased susceptibility to
      infection by Streptococcus pneumoniae. CONCLUSIONS: These findings indicate that
      Bam32 specifically couples an upstream signal to the IgG3 isotype heavy chain CSR
      and suggest that defects in Bam32 may account for the increased susceptibility to
      encapusulated organisms in a subset of immunodeficient patients.

PMID- 14588242
TI  - Abi, Sra1, and Kette control the stability and localization of SCAR/WAVE to
      regulate the formation of actin-based protrusions.
AB  - BACKGROUND: In animal cells, GTPase signaling pathways are thought to generate
      cellular protrusions by modulating the activity of downstream actin-regulatory
      proteins. Although the molecular events linking activation of a GTPase to the
      formation of an actin-based process with a characteristic morphology are
      incompletely understood, Rac-GTP is thought to promote the activation of
      SCAR/WAVE, whereas Cdc42 is thought to initiate the formation of filopodia
      through WASP. SCAR and WASP then activate the Arp2/3 complex to nucleate the
      formation of new actin filaments, which through polymerization exert a protrusive
      force on the membrane. RESULTS: Using RNAi to screen for genes regulating cell
      form in an adherent Drosophila cell line, we identified a set of genes, including
      Abi/E3B1, that are absolutely required for the formation of dynamic protrusions.
      These genes delineate a pathway from Cdc42 and Rac to SCAR and the Arp2/3
      complex. Efforts to place Abi in this signaling hierarchy revealed that Abi and
      two components of a recently identified SCAR complex, Sra1 (p140/PIR121/CYFIP)
      and Kette (Nap1/Hem), protect SCAR from proteasome-mediated degradation and are
      critical for SCAR localization and for the generation of Arp2/3-dependent
      protrusions. CONCLUSIONS: In Drosophila cells, SCAR is regulated by Abi, Kette,
      and Sra1, components of a conserved regulatory SCAR complex. By controlling the
      stability, localization, and function of SCAR, these proteins may help to ensure
      that Arp2/3 activation and the generation of actin-based protrusions remain
      strictly dependant on local GTPase signaling.

PMID- 14588243
TI  - Arthropod-like expression patterns of engrailed and wingless in the annelid
      Platynereis dumerilii suggest a role in segment formation.
AB  - The origin of animal segmentation, the periodic repetition of anatomical
      structures along the anteroposterior axis, is a long-standing issue that has been
      recently revived by comparative developmental genetics. In particular, a similar
      extensive morphological segmentation (or metamerism) is commonly recognized in
      annelids and arthropods. Mostly based on this supposedly homologous segmentation,
      these phyla have been united for a long time into the clade Articulata. However,
      recent phylogenetic analysis dismissed the Articulata and thus challenged the
      segmentation homology hypothesis. Here, we report the expression patterns of
      genes orthologous to the arthropod segmentation genes engrailed and wingless in
      the annelid Platynereis dumerilii. In Platynereis, engrailed and wingless are
      expressed in continuous ectodermal stripes on either side of the segmental
      boundary before, during, and after its formation; this expression pattern
      suggests that these genes are involved in segment formation. The striking
      similarities of engrailed and wingless expressions in Platynereis and arthropods
      may be due to evolutionary convergence or common heritage. In agreement with
      similarities in segment ontogeny and morphological organization in arthropods and
      annelids, we interpret our results as molecular evidence of a segmented ancestor
      of protostomes.

PMID- 14588244
TI  - The Sac1 lipid phosphatase regulates cell shape change and the JNK cascade during
      dorsal closure in Drosophila.
AB  - The Sac1 lipid phosphatase dephosphorylates several phosphatidylinositol (PtdIns)
      phosphates and, in yeast, regulates a diverse range of cellular processes
      including organization of the actin cytoskeleton and secretion. We have
      identified mutations in the gene encoding Drosophila Sac1. sac1 mutants die as
      embryos with defects in dorsal closure (DC). DC involves the migration of the
      epidermis to close a hole in the dorsal surface of the embryo occupied by the
      amnioserosa. It requires cell shape change in both the epidermis and amnioserosa
      and activation of a Jun N-terminal kinase (JNK) MAPK cascade in the leading edge
      cells of the epidermis [2]. Loss of Sac1 leads to the improper activation of two
      key events in DC: cell shape change in the amnioserosa and JNK signaling. sac1
      interacts genetically with other participants in these two events, and our data
      suggest that loss of Sac1 leads to upregulation of one or more signals
      controlling DC. This study is the first report of a role for Sac1 in the
      development of a multicellular organism.

PMID- 14588245
TI  - Evidence that Egfr contributes to cryptic genetic variation for photoreceptor
      determination in natural populations of Drosophila melanogaster.
AB  - One objective of quantitative genetics is to identify the nucleotide variants
      within genes that contribute to phenotypic variation and susceptibility [1]. In
      an evolutionary context, this means characterizing the molecular polymorphisms
      that modify the penetrance and expressivity of perturbed traits. A survey of
      association between 267 SNPs in almost 11 kb of the D. melanogaster Egfr and the
      degree of eye roughening due to a gain-of-function Egfr(E1) allele crossed into
      210 isogenic wild-type lines provides evidence that a handful of synonymous
      substitutions supply cryptic variation for photoreceptor determination. Ten sites
      exceed Bonferroni threshold for association in two sets of crosses to different
      Egfr(E1) backgrounds including a particularly significant cluster of sites in
      tight linkage disequilibrium toward the 3' end of the coding region. Epistatic
      interaction of this cluster with one other site enhances the expressivity of this
      haplotype. Replication of the strongest associations with an independent sample
      of 302 phenotypically extreme individuals derived from 1000 crosses of Egfr(E1)
      to freshly trapped males was achieved using modified case-control and
      transmission-disequilibrium tests. A tendency for the rarer alleles to have more
      disrupted eye development suggests that mutation-selection balance is a possible
      mechanism contributing to maintaining cryptic variation for Egfr.

PMID- 14588246
TI  - Peripheral, non-centrosome-associated microtubules contribute to spindle
      formation in centrosome-containing cells.
AB  - In centrosome-containing cells, microtubules utilized in spindle formation are
      thought to be nucleated at the centrosome. However, spindle formation can proceed
      following experimental destruction of centrosomes or in cells lacking
      centrosomes, suggesting that non-centrosome-associated microtubules may
      contribute to spindle formation, at least when centrosomes are absent. Direct
      observation of prometaphase cells expressing GFP-alpha-tubulin shows that
      peripheral, non-centrosome-associated microtubules are utilized in spindle
      formation, even in the presence of centrosomes. Clusters of peripheral
      microtubules moved into the centrosomal region, demonstrating that a centrosomal
      microtubule array can be composed of both centrosomally nucleated and peripheral
      microtubules. Peripheral bundles also moved laterally into the forming spindle
      between the spindle poles; 3D reconstructions of fixed cells reveal interactions
      between peripheral and centrosome-associated microtubules. The spindle pole
      component NuMA and gamma-tubulin were present at the foci of peripheral
      microtubule clusters, indicating that microtubules moved into the spindle with
      minus ends leading. Photobleach- and photoactivation-marking experiments of cells
      expressing GFP-tubulin or a photoactivatable variant of GFP-tubulin,
      respectively, demonstrate that microtubule motion into the forming spindle
      results from transport and sliding interactions, not treadmilling. Our results
      directly demonstrate that non-centrosome-associated microtubules contribute to
      spindle formation in centrosome-containing cells.

PMID- 14588247
TI  - Blockade of neurotransmission in Drosophila mushroom bodies impairs odor
      attraction, but not repulsion.
AB  - Olfaction can elicit a rich perceptual experience. It is not known, however,
      whether olfactory information is decomposed into various components and processed
      in distinct perceptual centers as in other sensory systems, such as vision, where
      neural representations of different visual sensations are segregated in different
      cortical regions, despite the fact that multiple structures of the primary
      olfactory cortex receive projections from the olfactory bulb. Here, we use
      Drosophila as a model to investigate whether different olfactory information may
      be processed in separate brain structures. Organizations of the peripheral
      olfactory system are remarkably similar from mammals to insects. As in
      vertebrates, the olfactory pathway in Drosophila follows similar convergence and
      divergence, and multiple high-order structures in the Drosophila brain, including
      the mushroom body (MB) and lateral horn (LH) of the protocerebrum, receive
      olfactory input. We specifically blocked neurotransmission in the MB while
      leaving the LH unaffected and examined its effect on olfactory avoidance and
      attraction behaviors. We show that blocking MB activity disrupted responses to
      attractive, but not repulsive, odors, and this finding suggests that attractive
      and repulsive olfactory information may be separately processed in higher
      olfactory centers of the Drosophila brain.

PMID- 14588248
TI  - Fat facets interacts with vasa in the Drosophila pole plasm and protects it from
      degradation.
AB  - Anterior-posterior patterning and germ cell specification in Drosophila requires
      the establishment, during oogenesis, of a specialized cytoplasmic region termed
      the pole plasm. Numerous RNAs and proteins accumulate to the pole plasm and
      assemble in polar granules. Translation of some of these RNAs is generally
      repressed and active only in pole plasm. Vasa (VAS) protein, an RNA helicase and
      a component of polar granules, is essential maternally for posterior patterning
      and germ cell specification, and VAS is a candidate translational activator in
      the pole plasm. VAS is stabilized within the pole plasm in that it is initially
      present throughout the entire embryo but strictly limited to the pole cells by
      the cellular blastoderm stage. hsp83 mRNA, which accumulates in the pole plasm
      through a stabilization-degradation mechanism, is another example. Here, we used
      a biochemical approach to identify proteins that copurify with VAS in crosslinked
      extracts. Prominent among these proteins was the ubiquitin-specific protease Fat
      facets (FAF), a pole plasm component [7], but one whose roles in posterior
      patterning and germ line specification have remained unclear. We present evidence
      that FAF interacts with VAS physically and reverses VAS ubiquitination, thereby
      stabilizing VAS in the pole plasm.

PMID- 14588249
TI  - Serotonin and Go modulate functional states of neurons and muscles controlling C.
      elegans egg-laying behavior.
AB  - From nematodes to humans, animals employ neuromodulators like serotonin to
      regulate behavioral patterns and states. In the nematode C. elegans, serotonin
      has been shown to act in a modulatory fashion to increase the rate and alter the
      temporal pattern of egg laying. Though many candidate effectors and regulators of
      serotonin have been identified in genetic studies, their effects on specific
      neurons and muscles in the egg-laying circuitry have been difficult to determine.
      Using the genetically encoded Ca(2+) indicator cameleon, we found that serotonin
      acts directly on the vulval muscles to increase the frequency of Ca(2+)
      transients. In contrast, we found that the spontaneous activity of the egg-laying
      motorneurons was silenced by serotonin. Mutations in G protein alpha subunit
      genes altered the responses of both vulval muscles and egg-laying neurons to
      serotonin; specifically, mutations in the G(q)alpha homolog egl-30 blocked
      serotonin stimulation of vulval muscle Ca(2+) transients, while mutations in the
      G(o)alpha homolog goa-1 prevented the silencing of motorneuron activity by
      serotonin. These data indicate that serotonin stimulates egg laying by directly
      modulating the functional state of the vulval muscles. In addition, serotonin
      inhibits the activity of the motorneurons that release it, providing a feedback
      regulatory effect that may contribute to serotonin adaptation.

PMID- 14588251
TI  - Not yet a GM nation.

PMID- 14588252
TI  - Gates foots a malaria bill.

PMID- 14588250
TI  - Actin-like proteins MreB and Mbl from Bacillus subtilis are required for bipolar
      positioning of replication origins.
AB  - Actin-like proteins MreB and Mbl are required for proper cell shape and for
      viability in B. subtilis and form dynamic helical filaments underneath the cell
      membrane. We have found that depletion of MreB and Mbl proteins leads to a rapid
      defect in chromosome segregation before a defect in cell shape becomes
      detectable. Under these conditions, the SMC chromosome segregation complex that
      is essential for proper chromosome arrangement and segregation loses its specific
      subcellular localization, and replication origins fail to localize in a regular
      bipolar manner as in wild type cells. Time-lapse microscopy showed that during
      depletion of MreB, origin regions can move towards the same cell pole, showing
      that bipolar orientation of origin separation is lost. Contrarily, depletion of
      three other cell shape determinants, MreC, MreD, or MreBH (the third B. subtilis
      actin homolog) had no effect on chromosome segregation but varying effects on
      cell morphology. Depletion of MreC and MreD resulted in formation of round cells,
      while depletion of MreBH led to formation of vibrio-shaped cells. The data show
      that actin proteins Mbl and MreB are required for proper chromosome segregation
      and that Mre proteins affect different aspects in cell shape.

PMID- 14588253
TI  - Plastic sex for a brittle star.

PMID- 14588254
TI  - David Goldstein.

PMID- 14588255
TI  - Heterochronic genes.

PMID- 14588256
TI  - Nuclear substructure and dynamics.

PMID- 14588257
TI  - Impairment of spatial cognitive function with preservation of verbal performance
      during spatial disorientation.

PMID- 14588258
TI  - Meiosis: when even two is a crowd.
AB  - Recent studies in Caenorhabditis elegans show that crossover interference, which
      usually limits the number of exchanges per meiotic bivalent to just 'one',
      requires the continuity of both homologs. One 'function' of crossover
      interference may be the prevention of crossover events that might not effectively
      hold homologs together.

PMID- 14588259
TI  - Plant reproduction: GABA gradient, guidance and growth.
AB  - How a pollen tube manages to navigate through the female tissues during plant
      reproduction has been a mystery. A new analysis of an Arabidopsis mutant has
      provided the strongest evidence yet that a GABA gradient may be a critical signal
      for correct targeting of the pollen tube.

PMID- 14588261
TI  - Motion processing: how low can you go?
AB  - Neurons at early stages in the visual system can only 'view' small parts of the
      visual world, impeding their ability to determine correctly an object's motion
      direction. New studies suggest that this 'aperture problem' is already solved by
      special neurons at the first stage of motion detection in primary visual cortex.

PMID- 14588260
TI  - Germ plasm: protein degradation in the soma.
AB  - Germ plasm is a specialized cytoplasm that is physically segregated to the
      germline cells during early embryogenesis. Recent results suggest that, in
      Caenorhabditis elegans, germ plasm is also prevented from accumulating in somatic
      lineages by a ubiquitin ligase that targets germ plasm proteins for degradation.

PMID- 14588262
TI  - Aging: the sins of the parents.
AB  - Yeast cells have an asymmetric, stem-cell-like division. As the mother cell ages
      it becomes 100 times more genetically unstable, but it is only the daughter cells
      that exhibit loss of heterozygosity; the latter effect is not connected to SIR2
      dependent aging, but seems to be accompanied by a loss of the DNA damage
      checkpoint.

PMID- 14588263
TI  - Mobile DNAs: the poacher turned gamekeeper.
AB  - The selfish DNA hypothesis imagines the genome as an ecological community, a
      collection of interacting DNA sequences with differing evolutionary origins and
      potentially different interests. We are now finding out more about the ways in
      which host sequences can enlist the help of formerly parasitic DNAs.

PMID- 14588264
TI  - Mitosis: long-range signals guide microtubules.
AB  - The formation of microtubule-derived structures is thought to involve nucleation
      in all directions and stabilization of microtubules that contact relevant
      targets. A recent study indicates, during mitosis, there may be a third step, in
      which microtubule growth is directed over long distances without physical contact
      between the target and microtubules.

PMID- 14588265
TI  - MicroRNAs: a role in plant development.
AB  - MicroRNAs are known to regulate development in Caenorhabditis elegans by
      translational repression of target genes. MiRNAs have now been shown to regulate
      developmental processes in plants, using both translational repression and
      cleavage of the target gene's RNA transcript.

PMID- 14588266
TI  - The cervical spine in juvenile chronic arthritis.
AB  - BACKGROUND CONTEXT: In patients with juvenile chronic arthritis (JCA) the
      cervical spine is often affected, leading to pain and functional limitations.
      PURPOSE: To describe the frequency of the radiographic abnormalities in the
      cervical spine of a large series of patients with JCA, examined after skeletal
      maturity. STUDY DESIGN: Consecutive patients with JCA, who had cervical spine
      radiographs available taken at adult age (>18 years) were included in the study
      from one outpatient clinic and one rheumatology ward in the Rheumatism Foundation
      Hospital, Heinola, Finland. PATIENT SAMPLE: The series consisted of 159 patients
      fulfilling the diagnostic criteria of the European League Against Rheumatism for
      JCA. OUTCOME MEASURES: Evaluation of cervical spine radiographs for inflammatory
      changes. METHODS: Inflammatory changes in the cervical spine radiographs were
      measured as well as the size of the fourth cervical vertebra. Patient records
      were studied. The statistical analysis was calculated by Student's t-test or Mann
      Whitney U test. RESULTS: In 98 cases (62%) some inflammatory changes were
      detected in the cervical spine. Apophyseal joint ankylosis was noted in 65
      patients (41%), anterior atlantoaxial subluxation in 27 (17 %) and atlantoaxial
      impaction in 39 (25 %). The fourth cervical vertebra was abnormally small in 41
      patients (26%). CONCLUSIONS: Radiographically, the most frequent inflammatory
      change in the cervical spine of patients with JCA was apophyseal joint ankylosis
      at multiple levels. Atlantoaxial impaction and anterior atlantoaxial subluxation
      were typical of the upper cervical spine. Clinically, these changes tend to limit
      neck movements. A small C4 vertebral body was seen in patients with early disease
      onset and short body stature.

PMID- 14588267
TI  - Effects of aging and spinal degeneration on mechanical properties of lumbar
      supraspinous and interspinous ligaments.
AB  - BACKGROUND CONTEXT: The effects of aging and spinal degeneration on the
      mechanical properties of spinal ligaments are still unknown, although there have
      been several studies demonstrating those of normal spinal ligaments. PURPOSE: To
      investigate the mechanical properties of the human posterior spinal ligaments in
      human lumbar spine, and their relation to age and spinal degeneration parameters.
      STUDY DESIGN/SETTING: Destructive uniaxial tensile tests were performed on the
      human supraspinous and interspinous ligaments at L4-5 level. Their mechanical
      properties were compared with age and spinal degeneration using several imaging
      modalities. PATIENT SAMPLE: Twenty-four patients with lumbar degenerative
      diseases on whom posterior surgeries were performed, with the age ranging from 18
      to 85 years. OUTCOME MEASURES: The ultimate load and elastic stiffness as
      structural properties, the degree of disc degeneration, range of segmental
      motion, the disc height, disc space narrowing ratio and degree of facet
      degeneration as the parameters of spinal degeneration. METHODS: Twenty-four
      supraspinous and interspinous ligaments at the L4-5 level were obtained from
      posterior surgeries of patients with lumbar degenerative disease. The mechanical
      tests of bone-ligament-bone complexes were performed in a uniaxial tensile
      fashion with a specially designed clamp device. The ultimate load and elastic
      stiffness were calculated as structural properties. The degree of disc
      degeneration, range of segmental motion, the disc height, disc space narrowing
      ratio and degree of facet degeneration were examined by using radiographs,
      computed tomography and magnetic resonance imaging. RESULTS: The average and SD
      value of ultimate load, elastic stiffness, tensile strength and elastic modulus
      were 203+/-102.9 N, 60.6+/-36.7 N/mm, 1.2+/-0.6 Mpa and 3.3+/-2.1 Mpa,
      respectively. A significant negative correlation was found between age and
      tensile strength (p= 0.02). The specimens with facet degeneration showed lower
      values in tensile strength and elastic modulus than those without facet
      degeneration (p<0.04). However, no correlation was found between disc-related
      parameters and tensile strength. CONCLUSIONS: The mechanical strength of human
      lumbar posterior spinal ligaments decreases with age and facet degeneration,
      particularly in the ligament substance.

PMID- 14588268
TI  - Pathogenesis and diagnosis of delayed vertebral collapse resulting from
      osteoporotic spinal fracture.
AB  - BACKGROUND CONTEXT: In recent years there have been an increasing number of
      reports on surgical cases involving delayed neurological deficits caused by
      vertebral collapse after osteoporotic vertebral fracture. PURPOSE: We do not yet
      know which patients are most susceptible to delayed vertebral collapse and
      subsequent neurological deficits, or whether this pathological condition can be
      prevented or predicted. In this study, we investigated the mechanism of
      progression and radiographic features characteristic of this disease, and we
      report here the predictive or risk factors for delayed osteoporotic vertebral
      collapse. STUDY DESIGN: Retrospectively, we investigated the pathogenesis and
      diagnosis of delayed vertebral collapse with neurological deficit resulting from
      osteoporosis. PATIENT SAMPLE: A total of 28 patients (7 men and 21 women) with
      neurological deficits resulting from vertebral collapse caused by osteoporotic
      vertebral fractures were the subjects for this study. OUTCOME MEASURES:
      Comparisons and investigations about clinical features and radiographic findings
      between the patient group of delayed vertebral collapse with neurological
      deficits and the group of osteoporotic spinal fracture with no neurological
      deficits. METHODS: The following factors were examined: the cause of injury; the
      length of time from injury, or the onset of pain, to the onset of neurological
      symptoms; radiographic findings obtained during the above period; the clinical
      course of vertebral fracture on plain X-ray films; time of appearance of the
      intravertebral cleft, and its localization and changes. RESULTS: Six patients
      were hospitalized and prescribed a period of 2 weeks of bed rest followed by the
      fitting of a corset; seven outpatients were corseted but not prescribed bed rest;
      15 patients were given medication only at an outpatient clinic. At radiography,
      intravertebral clefts were detected in 22 patients (79%) during the period from
      the appearance of pain to the onset of neurological deficit. In 14 patients (50%)
      who were radiographed every 1 to 2 weeks from the injury to the onset of
      neurological symptoms, the course of progression to collapse of the vertebral
      body could be observed. CONCLUSION: Initial correct diagnosis and immobilization
      are important in preventing the delayed collapse with neurological deficit. The
      presence of an intravertebral cleft and instability of the affected vertebra
      represent risk factors for vertebral collapse with neurological deficit,
      requiring careful observation.

PMID- 14588270
TI  - Current developments in spinal cord injury research.
AB  - BACKGROUND CONTEXT: Recent advances in neuroscience have opened the door for hope
      toward prevention and cure of the devastating effects of spinal cord injury
      (SCI). PURPOSE: To highlight the current understanding of traumatic SCI
      mechanisms, provide information regarding state-of-the-art care for the acute
      spinal cord-injured patient, and explore future treatments aimed at neural
      preservation and reconstruction. STUDY DESIGN/SETTING: A selective overview of
      the literature pertaining to the neuropathophysiology of traumatic SCI is
      provided with an emphasis on pharmacotherapies and posttraumatic experimental
      strategies aimed at improved neuropreservation and late neuroregenerative repair.
      METHODS: One hundred fifty-four peer-reviewed basic science and clinical articles
      pertaining to SCI were reviewed. Articles cited were chosen based on the relative
      merits and contribution to the current understanding of SCI neuropathophysiology,
      neuroregeneration, and clinical SCI treatment patterns. RESULTS: A better
      understanding of the pathophysiology and early treatment for the spinal cord
      injured patient has led to a continued decrease in mortality, decreased acute
      hospitalization and complication rates, and more rapid rehabilitation and re
      entry into society. Progressive neural injury results from a combination of
      secondary injury mechanisms, including ischemia, biochemical alterations,
      apoptosis, excitotoxicity, calpain proteases, neurotransmitter accumulation,
      lipid peroxidation/free radical injury, and inflammatory responses. Experimental
      studies suggest that the final posttraumatic neurologic deficit is not only a
      result of the initial impaction forces but rather a combination of these forces
      and secondary time-dependent events that follow shortly after the initial impact.
      CONCLUSIONS: Experimental studies continue to provide a better understanding of
      the complex interaction of pathophysiologic events after traumatic SCI. Future
      approaches will involve strategies aimed at blocking the multiple mechanisms of
      progressive central nervous system injury and promoting neuroregeneration.

PMID- 14588269
TI  - Skip laminectomy--a new treatment for cervical spondylotic myelopathy, preserving
      bilateral muscular attachments to the spinous processes: a preliminary report.
AB  - BACKGROUND CONTEXT: Techniques in current use for expansive laminoplasty
      operations (ELAP) on the cervical spine damage the extensor mechanisms, resulting
      in restriction of neck motion, loss of lordosis and persistent axial pains.
      PURPOSE: This article introduces a new surgical technique called skip
      laminectomy, which reduces morbidity after decompression of the cervical spinal
      canal. STUDY DESIGN/SETTING: A prospective study is presented of all patients
      with multilevel cervical spondylotic myelopathy (CSM), treated by this new
      procedure between December 1998 and March 2000. PATIENT SAMPLE: Since December
      1998, 61 patients with CSM have undergone the procedure, of whom 24 (13 men and
      11 women) were selected for this study. Follow-up periods ranged from 12 to 25
      months, with an average of 18 months. Average age at operation was 69 years
      (range, 50 to 82 years). Eighteen patients with CSM on whom C3-C7 open-door
      laminoplasties had been performed by the author before 1998 were selected as
      controls for study of postoperative atrophy of the deep extensor cervical
      muscles. There were 11 men and 7 women, average age 67 years (range, 45 to 81).
      OUTCOME MEASURES: Axial symptoms and Japanese Orthopaedic Association (JOA)
      scores were recorded. Pre- and postoperative ranges of neck motion were measured
      on lateral flexion and extension radiographs. Pre- and postoperative cervical
      curvature indexes were calculated according to Ishihara's method. For
      quantitative analysis of damage to the posterior cervical muscles, atrophy rates
      were calculated from cross-sectional areas of the deep extensor muscles on the
      pre- and postoperative axial magnetic resonance imaging. METHODS: In skip
      laminectomy, standard laminectomies are performed at selected levels, combined
      with partial laminectomies of the cephalad halves of laminae at other selected
      levels, where the muscular attachments to the spinous processes are left
      undisturbed. Instead of a standard laminectomy, an interlaminar decompression can
      be performed at levels where the anterior spinal cord compression is
      insignificant. It is accomplished by simply removing the cephalad half of the
      inferior lamina and ligamentum flavum without detaching the semispinalis cervicis
      and multifidus muscles from the adjacent spinous processes. RESULTS: Using JOA
      scores, the average recovery rate was 61.0%. None of the patients complained of
      persistent axial symptoms. The postoperative range of flexion-extension motion
      averaged 97% of the preoperative measures. The cervical curvature index was
      reduced in 1 of the 24 patients. The atrophy rate of the deep extensor muscles
      after skip laminectomy was 20% of that seen after open-door laminoplasty.
      CONCLUSIONS: Skip laminectomy for cervical spinal canal decompression is less
      invasive than conventional laminectomy and ELAP. It is effective in preventing
      postoperative problems, such as persistent axial symptoms, restriction of neck
      motion and loss of cervical lordosis.

PMID- 14588271
TI  - Computed tomography validating bony ingrowth into fibula strut allograft: a
      criterion for fusion.
AB  - BACKGROUND CONTEXT: Static and dynamic X-ray studies routinely determine whether
      or not fusion of a fibula strut allograft has occurred after multilevel anterior
      corpectomy with fusion (ACF) combined with posterior wiring and fusion (PWF).
      PURPOSE: Two-dimensional (2D) computed tomography (CT) studies were assessed for
      documentation of bony ingrowth into fresh frozen fibula strut allograft to
      constitute an additional sign of fusion. STUDY DESIGN/SETTING: This was a
      prospective, nonrandomized study, which was conducted at a university medical
      center. PATIENT SAMPLE: Eighteen patients with moderate to severe myelopathy
      undergoing circumferential cervical surgery for ossification of the posterior
      longitudinal ligament and spondylostenosis were evaluated. OUTCOME MEASURES:
      Static and dynamic X-rays and 2D CT examinations were performed in 18 patients 3
      and 6 months after circumferential cervical procedures. METHODS: Fusion was
      assessed on static and dynamic X-rays, and 2D CT studies performed in 18 patients
      following average 2.9 level anterior corpectomy with fusion (ACF) with posterior
      wiring and fusion (PWF) (C2-T1) with halo application. Routine fusion criteria on
      static radiographs included the documentation of bony trabeculation and absence
      of bony lucency at the graft/vertebral end plate interface. Routine dynamic X-ray
      criteria of fusion mandated that less than 3.5 mm of translation, less than 20
      degrees of angulation, and less than 1 mm of motion be observed between adjacent
      spinous processes. Here, a potential additional 2D CT criterion for fusion,
      progressive bony ingrowth into the central shaft of a fibula strut allograft, was
      investigated on 3 and 6 month postoperative 2D CT examinations using direct
      measurement of Hounsfield units. Telescoping (mm) was also differentiated from
      ingrowth into the bony shaft based on a comparison of immediate, 3 and 6 month
      postoperative CT studies. RESULTS: Immediate postoperative baseline 2D CT studies
      revealed no bone within the central canal but an average of less than 1 mm of
      cephalad and 2.3 mm of caudad graft telescoping. Within 6 postoperative months,
      2D CT studies demonstrated an average of 3.5 mm of superior and 4.6 mm of
      inferior bony ingrowth (confirmed by measuring 500 to 900 Hounsfield units) into
      the central fibula canal of 17 of 18 patients (94%). Seventeen had
      routine/dynamic X-ray and CT studies confirming fusion. CONCLUSIONS: Two
      dimensional CT evidence of bony ingrowth into the central canal of fibula strut
      allografts after multilevel ACF/PWF provided an additional means of quantifying
      the extent of fusion.

PMID- 14588272
TI  - Occipital-cervical fusion using the Locksley intersegmental tie bar technique:
      long-term experience with 19 patients.
AB  - BACKGROUND CONTEXT: The management of lesions at the craniocervical junction
      presents unique difficulties for the spine surgeon. The complexity of this region
      creates a variety of mechanical forces that challenge any fusion construct. An
      understanding of the ligamentous, bone and vascular structures in this region is
      critical. PURPOSE: To describe a method of occipital-cervical fusion with long
      term follow-up. STUDY DESIGN/SETTING: Retrospective case series. PATIENT SAMPLE:
      Twenty-one consecutive patients with craniocervical compression and/or
      instability who were treated using the Locksley intersegmental tie bar technique.
      OUTCOME MEASURES: Neurologic function, fusion, postoperative complications.
      METHODS: Patients with craniocervical instability underwent occipital-cervical
      fusion using the Locksley intersegmental tie bar technique. The pathologic
      processes causing compression and/or instability at the craniocervical junction,
      as well as the patients' pre- and postoperative neurologic status, are reported.
      RESULTS: Solid fusion was attained in all 19 patients surviving at 2 years. Two
      patient deaths were reported in this series in the early postoperative period
      because of systemic disease. CONCLUSIONS: This approach allows for rigid,
      immediate stabilization of this region. An external orthosis is most often not
      required. This technique has unique applicability to patients where the normal
      ligamentous and bone structures are weakened because of underlying disease or
      injury.

PMID- 14588273
TI  - Direct repair of spondylolytic defects in young competitive athletes.
AB  - BACKGROUND CONTEXT: Operative treatment of symptomatic spondylolysis is rare. A
      variety of surgeries have been described. In general, reported operative success
      rates are high, although in most studies the successful return to sport of the
      competitive athlete is not detailed. PURPOSE: To review outcome, specifically
      return to sport, in a group of competitive athletes after direct pars repair for
      symptomatic spondylolysis. STUDY DESIGN/SETTING: This was a retrospective case
      series of a single surgeon. PATIENT SAMPLE: Series of four athletes who underwent
      direct pars repair over an 18-month period. OUTCOME MEASURES: Return to their
      sport. METHODS: Chart review of all patients who had undergone a single-level
      pars repair over an 18-month period. All patients had normal discs above the
      level of the repair. Postoperative clinical course was determined for all
      patients. RESULTS: The patients participated in different sports. All were able
      to return to their presymptomatic level of activity with no restriction. One had
      periodic low back pain that required nonsteroidal anti-inflammatory medicine as
      needed. The others were entirely asymptomatic. CONCLUSIONS: This small series
      suggests that with specific inclusion criteria, a select group of motivated
      athletes can expect to return to their sport after direct pars repairs for
      symptomatic spondylolysis that has failed conservative treatment.

PMID- 14588274
TI  - Electrical stimulation of spinal fusion: a scientific and clinical update.
AB  - BACKGROUND CONTEXT: For over two decades, a number of electrical stimulation
      devices have achieved increasing acceptance as adjuncts to lumbar spinal fusion.
      Direct current electrical stimulation, pulsed electromagnetic fields and more
      recently capacitive coupling have been shown to have varying effectiveness when
      used to increase the success of lumbar spinal fusion. PURPOSE: The various
      electrical stimulation devices will be reviewed with respect to the available
      basic science evidence validating their use as spinal fusion adjuncts, as well as
      a review of the current clinical data available to allow not only a discussion of
      their overall clinical applicability, but more specifically their use in specific
      spinal disorders and spinal fusion techniques. METHODS: The existing peer
      reviewed scientific literature will be used to ascertain the scientific and
      clinical efficacy of electrical stimulation to enhance lumbar spinal fusion.
      CONCLUSION: Electrical stimulation devices have emerged as valid adjuncts to
      attaining a solid lumbar spinal fusion. However, not all stimulators are equally
      scientifically effective nor are they equally effective clinically in achieving
      increased fusion success.

PMID- 14588275
TI  - Thoracic kyphoscoliosis resembling neurofibromatosis: a case report focusing on
      subfascial instrumentation.
AB  - BACKGROUND CONTEXT: The management of early-onset progressive scoliosis is
      controversial. PURPOSE: To describe the unusual surgical management of a young
      female with an early-onset progressive, short, angular kyphoscoliosis resembling
      neurofibromatosis. STUDY DESIGN: A case report reviewing the treatment of an
      unusual occurrence of kyphoscoliosis. METHODS: After compliant Milwaukee brace
      wear had failed to stop deformity progression, surgical management including
      segmental anterior and posterior T5-T10 arthrodesis, and posterior T3-L4
      subfascial rod instrumentation was performed at age 4 years and 6 months. After
      10 rod lengthenings, segmental anterior T10 to L3 arthrodesis and posterior T3-L4
      instrumentation and arthrodesis were done at age 11 years and 5 months. RESULTS:
      From preoperative to 3-year postoperative definitive surgery, her T3 to L4
      instrumented spine length increased by 9.5 cm; 4 cm after the initial surgery, 3
      cm between the initial surgery and the definitive surgery and 2.5 cm after the
      definitive surgery. From preoperative to latest follow-up, her thoracic scoliosis
      was reduced from 89 to 31 degrees, her thoracolumbar compensatory scoliosis from
      59 to 37 degrees and her kyphosis from 70 to 17 degrees. CONCLUSIONS: The
      combination of early definitive anterior and posterior major curve arthrodesis
      with a subfascial rod lengthening program to control the remainder of the
      thoracolumbar spine was a satisfactory solution for this unusual case of early
      onset, progressive, short, angular kyphoscoliosis.

PMID- 14588279
TI  - Key to diagnosis of cervicogenic headache is the examination of the anterior
      cervical spine.

PMID- 14588280
TI  - Comment on John A. McCulloch's letter.

PMID- 14588282
TI  - Emerging technologies in spine surgery.

PMID- 14588283
TI  - Athena, Aesculapius and beyond: the art of mentoring: 2001 North American Spine
      Society presidential address.

PMID- 14588284
TI  - Osseointegration of autograft versus osteogenic protein-1 in posterolateral
      spinal arthrodesis: emphasis on the comparative mechanisms of bone induction.
AB  - BACKGROUND CONTEXT: Recent studies have documented increased fusion success
      afforded by bone morphogenetic proteins versus autogenous graft for
      posterolateral spinal arthrodesis. PURPOSE: The current study was designed to
      investigate the time-course maturation processes of lumbar posterolateral
      arthrodeses performed with Osteogenic Protein-1 (Stryker Biotech, Inc.,
      Hopkinton, MA, USA) (rhOP-1) versus "gold standard" autograft. STUDY DESIGN: The
      primary focus of this study was to compare the histologic mechanisms of
      posterolateral osseointegration produced by "hot topic" growth factors. METHODS:
      A total of 36 coonhounds were equally divided into one of four postoperative time
      periods of 4, 8, 12 and 24 weeks (nine animals per period). Posterolateral
      arthrodesis treatments included 1) autograft alone, 2) autograft plus rhOP-1, or
      3) rhOP-1 alone. The treatments and animals were divided such that a value of n=6
      was obtained for each treatment group per time period and no one animal received
      the same treatment at both operative sites. Functional spinal unit (FSU) fusion
      status was assessed using radiographic analysis, biomechanical testing and
      undecalcified histopathologic and histomorphometric analyses. RESULTS:
      Radiographic differences in fusion maturation between the treatment groups were
      evident as early as the 4-week time interval and continued through the 24-week
      time period. The Osteogenic Protein-1 treatments demonstrated an accelerated rate
      of radiographic fusion by 4 weeks, which plateaued after the 8-week time period
      (22% autograft, 88% autograft/rhOP-1 and 66% rhOP-1). In contradistinction, the
      so-called "gold standard" autograft alone treatments reached a maximum of 50%
      fusion by the 6-month interval. Biomechanical testing of the FSUs indicated lower
      flexion-extension and axial rotation range of motion levels for both rhOP-1
      treatments versus autograft alone at the 8- and 12-week time periods,
      respectively (p<.05). Histomorphometric analysis yielded no difference in the
      posterolateral trabecular bone area (mm(2)) between the three treatments (p>.05),
      and histopathology indicated no significant histopathologic changes. The most
      distinctive finding in this study deals with the mechanisms of posterolateral
      ossification. Based on plain and polarized light microscopy, bone induction and
      development for the rhOP-1 treatments, with and without autograft, was the result
      of intramembranous ossification, whereas the process of osseointegration for
      autograft alone was endochondral bone formation. By the 24-week interval, no
      discernable differences in trabecular histomorphology were evident based on the
      different mechanisms of ossification. CONCLUSIONS: This serves as the first study
      to document the mechanisms of bone induction and fusion maturation between
      posterolateral arthrodeses treated with autograft versus rhOP-1. The histological
      data served to corroborate the radiographic and biomechanical findings, because
      the rhOP-1 treatments consistently demonstrated increased fusion rates and lower
      range of motion levels compared with the autograft group, particularly at the 8
      week postoperative time period. The improvements in these fusion criteria for
      Osteogenic Protein-1 versus autograft were considered secondary to the differing
      mechanisms of bone induction. When implanted for posterolateral arthrodesis, rhOP
      1 induces an intramembranous healing response, obviating the need for the
      cartilage intermediate phases found in endochondral bone development. The
      mechanism of increased speed and incidence of fusion using growth factors (rhOP
      1) is delineated by this comprehensive study of preferential intramembranous
      ossification.

PMID- 14588285
TI  - Provocative discography in volunteer subjects with mild persistent low back pain.
AB  - BACKGROUND CONTEXT: Whether discographic injections would be positive in subjects
      with benign persistent "backache" who are not seeking treatment is unknown. This
      information is important, because benign backache undoubtedly co-exists in
      patients with chronic low back pain (CLBP) illness that is not discogenicin
      origin. If these subjects had a high rate of positive discography, the high
      background incidence of common backache would allow many positive tests in
      patients in whom discogenic processes were unrelated to their severe CLBP
      illness. Conversely, if subjects with benign low back pain rarely if ever had
      significant concordant pain reproduction on disc injections, the basic tenet of
      discographic diagnosis would be strengthened. PURPOSE: To compare, using a strict
      experimental design, the relative pain and concordancy response to provocative
      discography in subjects with clinically insignificant "backache" and clinical
      subjects with CLBP illness considering surgical treatment. STUDY DESIGN:
      Comparison of experimental disc injections in subjects with persistent mild
      backache and those with chronic low back pain (CLBP) illness. PATIENT SAMPLE:
      Twenty-five subjects with mild persistent low back pain (LBP) were recruited for
      an experimental discography study. Subjects were recruited from a clinical study
      of patients having had cervical spine surgery. Inclusion criteria required that
      subjects not be receiving or seeking medical treatment for LBP, be taking no
      medications for backache, have no activity restrictions because of LBP, and have
      normal psychometric scores. To more closely approximate the pain behavior in CLBP
      illness, 50% (12) of the "backache" group were recruited with a chronic painful
      condition (neck/shoulder) unrelated to the low back. CLBP subjects, patients
      coming to discography for consideration of surgical treatment, were used as
      control subjects. OUTCOME MEASURES: Results of discography were determined using
      the criteria of Walsh et al.: pain response of 3 or greater, two or more pain
      behaviors, a negative "control" discographic injection, and a similar or exact
      concordancy rating. METHODS: Discography was performed on experimental subjects
      and control patients. Experienced raters, who were blinded to control versus
      experimental status of the subjects, scored the magnetic resonance image,
      discogram, psychometric tests and discography videotapes of the subjects' pain
      behavior. RESULTS: Thirteen of 25 volunteer subjects had pain rated as "bad" or
      worse with disc injection. There were 12 painful and fully concordant disc
      injections in 9 of these 25 "backache" subjects (36%). These injections met all
      the Walsh et al. criteria for a positive diagnosis of discogenic pain. All
      positive discs had annular disruption to or through the outer annulus. Of the 9
      subjects with positive discograms, 3 had no chronic pain states and 6 did. All
      subjects with positive injections had negative control discs. In comparison, in
      52 subjects with CLBP illness 38 (73%) had at least one positive disc injection.
      CONCLUSIONS: In a group of volunteer subjects with persistent "backache," 36%
      were found to have significant pain on disc injection, which is reported to be
      concordant with their usual pain. The presence of positive concordant pain
      responses and negative control discs in 33% of subjects without CLBP illness
      seriously challenges the specificity of provocative discography in identifying a
      clinically relevant spinal pathology.

PMID- 14588286
TI  - Role of Na(+)-Ca(2+) exchanger after traumatic or hypoxic/ischemic injury to
      spinal cord white matter.
AB  - BACKGROUND CONTEXT: Spinal cord injury is a devastating condition in which
      clinical disability results from demyelination of white matter tracts. Changes in
      glial-axonal signaling, and enhanced Ca(2+) channel activity with excessive
      accumulation of intracellular Ca(2+), is a common phenomenon after
      hypoxia/ischemia or mechanical trauma to spinal cord dorsal column white matter
      tracts leading to irreversible injury. PURPOSE: In the present study we examined
      the role of Na(+)-Ca(2+) exchanger (NCX) at physiological temperatures after
      hypoxia/ischemia and compressive injury to spinal cord dorsal column white matter
      in vitro. STUDY DESIGN: A 30-mm length of dorsal column was isolated from the
      spinal cord of adult rats, pinned in an in vitro recording chamber (maintained at
      37 degrees C) and injured by exposure to a hypoxic atmosphere for 60 minutes or
      compressed with a modified aneurysm clip (2-gm closing force) for 15 seconds. The
      functional integrity of the dorsal column was monitored electrophysiologically by
      quantitatively measuring the compound action potential (CAP) with glass
      microelectrodes. RESULTS: The mean CAP decreased to 49.5 +/- 5.7% and 49.4 +/-
      2.6% of control (p<.05) after hypoxia/ischemia and compressive injury,
      respectively. KB-R7943, a potent, selective NCX reverse mode inhibitor,
      significantly promoted greater recovery of CAP amplitude to 82.0 +/- 10.0% and
      70.8 +/- 10.7% of control (p<.05) after hypoxic/ischemic or compressive injury to
      dorsal column white matter, respectively, when applied at 10 microM
      concentration. Bepridil (Research Biochemical Inc., Natick, MA, USA) (a less
      selective NCX inhibitor), when applied at 10 microM and 50 microM concentration
      promoted CAP amplitude recovery only to 46.8 +/- 7.8% and 29.9 +/- 3.3% of
      control, respectively, after hypoxic/ischemic injury to dorsal column white
      matter. Western blot analysis identified NCX presence with positive
      immunolabeling of 160 kD and 120 kD NCX proteins in the spinal cord white matter.
      CONCLUSION: In conclusion, at physiological temperature NCX activation plays an
      important role in intracellular calcium overload after hypoxic/ischemic and
      compressive injury to spinal cord dorsal column white matter in vitro.

PMID- 14588287
TI  - Transforaminal endoscopic decompression for radiculopathy secondary to intracanal
      noncontained lumbar disc herniations: outcome and technique.
AB  - BACKGROUND CONTEXT: In 1973 Kambin and Gellman introduced the concept of
      percutaneous posterolateral extracanal approach in the management of
      radiculopathy secondary to lumbar disc herniation (LDH). This new surgical
      approach was recognized as potentially even less invasive compared with the
      microscope-assisted transcanal technique. However, the development of the
      posterolateral extracanal approach has witnessed a slow and complicated technique
      and equipment evolution. PURPOSE: To report the surgical outcome, complications
      and technique of decompressing radiculopathy secondary to noncontained intracanal
      LDH using percutaneous extracanal access, the transforaminal endoscopic approach.
      STUDY DESIGN/SETTING: Consecutive cases of LDHs from L3-S1 who had at least 1
      year postoperative follow-up were included in this retrospective review. PATIENT
      SAMPLE: Two hundred nineteen patients met inclusion criteria. There were 136
      (62.1%) male patients, average age 41.5 years, and 83 (37.9%) female patients,
      average age 42.5 years. The age range was 17 to 71 years. METHODS: Two outcome
      measures were used. The first part was a surgeon-performed assessment. The second
      used a patient-based outcome questionnaire. OUTCOME MEASURES: The surgeon's
      retrospective assessment of excellent, good, fair and poor is a modified MacNab
      classification. The same terminology is used in the patient-based outcome
      questionnaire. Poor outcome resulting from technique failure is identified.
      RESULTS: Two hundred nineteen patients met the inclusion criteria. One hundred
      ninety-three patients also send back their completed questionnaire. The surgeon
      graded 88% percent of the 219 patients had a good or excellent result and the
      questionnaire subgroup 91.2%. The fair results were 5% of the 219 patients, 3.6%
      for the questionnaire patients. The poor results were 6.8% of the 219 patients
      and 5.2% for the questionnaire subgroup. The overall complication rate was 2.7%
      and missed fragment rate 0.9%. CONCLUSIONS: Noncontained intracanal LDH fragments
      are accessible using the transforaminal endoscopic technique and equipment
      described. Retrospective outcome reviews of our clinical material showed results
      comparable to the reported findings in the literature for both the endoscopic and
      open transcanal decompression techniques.

PMID- 14588288
TI  - Scheuermann kyphosis: long-term follow-up.
AB  - BACKGROUND CONTEXT: There is considerable controversy as to the optimal treatment
      of Scheuermann kyphosis. Proposed modalities have included exercise, bracing and
      surgery. PURPOSE: The purpose of this study was to document the functional
      capacity and radiographic findings in adults who have been previously treated for
      Scheuermann kyphosis. STUDY DESIGN: A cohort study of all patients with
      Scheuermann kyphosis treated in a single institution using three different
      treatment modalities: exercise and observation, Milwaukee bracing and surgical
      fusion using the Harrington Compression System. PATIENT SAMPLE: Sixty-three
      patients were evaluated at a mean of 14 years after treatment (10 to 28 years).
      OUTCOME MEASURES: Two different functional evaluation instruments were used.
      Radiographic evaluation was carried out in 38 patients (60%). METHODS: Patient
      interviews were conducted using a specially designed questionnaire. Patients were
      then asked to undergo standing radiographs. Patients were divided into groups
      depending on the location of their kyphosis and the manner in which they had been
      treated. Standard statistical analysis was then carried out. RESULTS: At time of
      follow-up evaluation there were no differences in marital status, general health,
      education level, work status, degree of pain and functional capacity between the
      various curve types, treatment modality and degree of curve. Patients treated by
      bracing or surgery did have improved self-image, which they attributed to their
      treatment. Patients with kyphotic curves exceeding 70 degrees at follow-up had an
      inferior functional result. At time of final follow-up there were no statistical
      differences in degree of kyphosis and mode of treatment. CONCLUSIONS: By
      carefully selecting the appropriate treatment for patients with Scheuermann
      kyphosis on the basis of the patient's age, spinal deformity and the severity of
      back pain, it is possible to achieve a similar functional result at long-term
      follow-up. Despite different treatment protocols, patients with Scheuermann
      kyphosis tend to achieve a similar functional result at long-term follow-up.

PMID- 14588289
TI  - Aging of the elastic and collagen fibers in the human cervical interspinous
      ligaments.
AB  - BACKGROUND CONTEXT: The ligaments consist of collagen bands intermingled with
      elastic fibers that support hundreds of pounds of stress per square inch. In the
      spine the basic functional unit comprises vertebrae, intervertebral disc and
      ligament tissues. The interspinous ligaments with the function of limiting the
      spine flexion are exposed to a traumatic and degenerative process that promotes
      pain or instability. It has been shown that aging induces structural changes to
      capsular, fascial and ligamentous structures, mainly to the elastic and collagen
      fibers. However, the relative changes with age in elastic and collagen fibers
      have not been quantified. PURPOSE: Examine the changes in the arrangement and
      amount of the elastic and collagen fibers of the human cervical interspinous
      ligament and attempt to correlate them with age. STUDY DESIGN/SETTING:
      Histomorphometric analysis of ligament samples harvested during surgery. PATIENT
      SAMPLE: We studied the dorsal portion of this ligament from 17 patients aged 16
      to 69 years. OUTCOME MEASURES: Fraction of collagen and elastic fibers with
      linear regression analysis correlating fraction versus age. METHODS: The elastic
      and collagen fibers were identified by selective staining methods, and a blinded
      investigator using an image analysis system performed the histomorphometry.
      RESULTS: There is an age-related progressive increase in collagen and mature and
      elaunin elastic fibers responsible to elasticity. However, these elastic fibers
      showed structural degenerative changes with aging. Furthermore, there is an age
      related decrease of oxytalan elastic fibers responsible to resistance.
      CONCLUSIONS: The aged interspinous ligament showed loss of elasticity that could
      alter the flexion limiting of the vertebral column.

PMID- 14588290
TI  - Anterior lumbar interbody fusion with titanium mesh cages, coralline
      hydroxyapatite, and demineralized bone matrix as part of a circumferential
      fusion.
AB  - BACKGROUND CONTEXT: Anterior lumbar interbody fusion (ALIF) has become one of the
      primary choices for eliminating motion between vertebral segments in patients
      with severe discogenic pain and other lumbar pathologies. Autograft is the gold
      standard for spinal fusion. However, multiple authors have reported complication
      and morbidity rates associated with iliac crest harvesting to be as high as 25%.
      Drawbacks to the use of allograft in the anterior column include slower
      incorporation rates, the possibility for disease transmission, increasing cost
      resulting from stringent processing and unavailability on a worldwide basis
      resulting from religious and economic concerns. PURPOSE: To determine the
      clinical and arthrodesis efficacy of coralline hydroxyapatite as an
      osteoconductive bone graft substitute in the anterior lumbar spine using a
      titanium mesh cage. STUDY DESIGN: A series of 50 patients returning for long-term
      prospective follow-up, implanted with titanium mesh cages filled with coralline
      hydroxyapatite and demineralized bone matrix for ALIF as part of a
      circumferential fusion. PATIENT SAMPLE: Long-term clinical and radiographic
      follow-up were examined for the first 50 patients undergoing this technique by
      one surgeon. OUTCOME MEASURES: Pain was measured with a visual analog scale and
      function was measured with the Oswestry Disability Index. METHODS: All 50
      patients underwent successful ALIF with titanium mesh cages, coralline
      hydroxyapatite and demineralized bone matrix, as well as an autologous
      posterolateral fusion with rigid posterior instrumentation. Patients filled out
      follow-up questionnaires and appropriate radiographs were taken. RESULTS: A solid
      fusion rate of 96% was achieved. Mean pain decrease was 60% overall. A total of
      70% of all patients either returned to work or to full home activities at a mean
      of 8 months after surgery. Ninety percent felt the surgery was successful.
      CONCLUSIONS: The combination of titanium mesh cages, coralline hydroxyapatite and
      demineralized bone matrix is effective for anterior interbody fusion of the
      lumbar spine when used as part of a rigidly instrumented circumferential fusion.

PMID- 14588291
TI  - Paraplegia after lumbosacral nerve root block: report of three cases.
AB  - BACKGROUND CONTEXT: Lumbar nerve root blocks and epidural steroid injections are
      frequently employed in the management of degenerative conditions of the lumbar
      spine, but relatively few papers have been published that address the
      complications associated with these interventions. Serious complications include
      epidural abscess, arachnoiditis, epidural hematoma, cerebrospinal fluid fistula
      and hypersensitivity reaction to injectate. Although transient paraparesis has
      been described after inadvertent intrathecal injection, an immediate and lasting
      deficit has not been previously described as sequelae of a nerve root block.
      PURPOSE: We present three cases in which either persisting paraplegia or
      paraparesis occurred immediately after administration of a lumbar nerve root
      block and propose a mechanism for this devastating but previously unreported
      complication. STUDY DESIGN/SETTING: Case reports of three patients. PATIENT
      SAMPLE: Three patients, two women and one man ranging in age from 42 to 64 years,
      underwent three procedures performed at three different facilities, in the hands
      of two different injectionists. In each instance, penetration of the dura was not
      thought to have occurred. In two procedures the needles were placed
      transforamenally, one at L3-4 on the left and one at L3-4 on the right, and in
      the third the needle tip was placed immediately lateral to the S1 nerve root.
      OUTCOME MEASURES: Patient follow-up data from medical office records. METHODS: In
      each case, needle placement was verified with injection of a contrast media in
      conjunction with either computerized tomography or biplanar fluoroscopy. No
      backbleeding or cerebrospinal fluid was encountered upon aspiration in any of the
      procedures. Magnetic resonance imaging (MRI) was performed within 48 hours of
      injury in all patients. RESULTS: In each patient, paraplegia suddenly ensued
      after instillation of the steroid solution and, in each instance, postprocedure
      MRI revealed increased signal in the low thoracic spinal cord on T2-weighted
      imaging consistent with edema. The sudden onset of neurological deficit and the
      imaging changes noted in the spinal cord point to a vascular explanation for
      these injuries. We postulate that in these patients the spinal needle either
      penetrated or caused injury to an abnormally low dominant radiculomedullary
      artery, a recognized anatomical variant. This vessel, also known as the artery of
      Adamkiewicz, in 85% of individuals arises between T9 and L2, usually from the
      left, but in a minority of people may arise from the lower lumbar spine and
      rarely even from as low as S1. The artery of Adamkiewicz travels with the nerve
      root through the neural foramen and irrigates the anterior spinal artery. Injury
      of it or injection of particulate matter into it, as what may happen with the
      commonly used epidural steroid injectates, may result in infarction of the lower
      thoracic spinal cord, producing the clinical and imaging findings seen in these
      three patients. CONCLUSIONS: We present the cases of three patients who had
      lasting paraplegia or paraparesis after the performance of a nerve root block. We
      propose that the mechanism for this rare but devastating complication is the
      concurrence of two uncommon circumstances, the presence of an unusually low
      origin of the artery of Adamkiewicz and an undetected intraarterial penetration
      of the procedure needle.

PMID- 14588293
TI  - Spinal injections: past, present and future.

PMID- 14588292
TI  - Minimally invasive treatment of osteoporotic vertebral body compression
      fractures.
AB  - BACKGROUND CONTEXT: Seven hundred thousand osteoporotic compression fractures
      occur yearly. Approximately 260,000 lead to severe pain, and 150,000 require
      hospital admissions. Associated with the fractures are increased loss of
      pulmonary function (90% decreased forced vital capacity per fracture level) and
      an increase in gastrointestinal complications (early satiety, and therefore
      malnutrition) and increased mortality (greater than that associated with
      osteoporotic hip fractures). New treatments available for these painful disorders
      include kyphoplasty and vertebroplasty. The injections of polymethylmethacrylate
      into the vertebrae (vertebroplasty technique) decrease pain and improve function.
      Kyphoplasty (percutaneous placement of a balloon tamp to improve height and
      create a void, and then the filling of this void with cement) improves function,
      decreases pain and helps realign the spine. PURPOSE: To compare kyphoplasty and
      vertebroplasty, and assess their various merits, treatment indications, and
      outcomes. STUDY DESIGN/SETTING: Literature review with presentation of early
      results of a national, clinical study. METHODS: Literature review for overview.
      Retrospective chart/patient review for clinical data presented on kyphoplasty.
      RESULTS: Ninety-five percent of individuals treated for painful osteoporotic
      compression fractures have significant improvement in symptoms and function after
      kyphoplasty or vertebroplasty. Kyphoplasty improves vertebral body height and
      kyphotic alignment by 50%, if performed within 3 months of the onset of the
      fracture collapse. CONCLUSIONS: Vertebroplasty and kyphoplasty both have roles in
      the treatment of painful osteoporotic compression fractures. Only kyphoplasty
      helps improve height and kyphosis, which should help prevent pulmonary and
      gastrointestinal complications.

PMID- 14588294
TI  - Three-dimensional computed tomographic volume rendering techniques in endoscopic
      thoracoplasty.
AB  - BACKGROUND CONTEXT: Thoracoplasty is occasionally necessary to achieve an
      acceptable cosmetic result in the presence of a rib hump, especially in
      previously fused young adults with scoliosis. This usually requires the resection
      of four to five rib segments, and the morbidity associated with open posterior
      resection or of open anterior resection by means of thoracotomy is often
      considerable, apart from leaving an unsightly scar. We thought the use of an
      endoscopic internal rib resection technique would achieve the desired result with
      less morbidity. Our experience with using the technique of three-dimensional (3
      D) computed tomographic (CT) volume rendering to plan our portals and releases
      for endoscopic scoliosis correction led us to believe the same techniques could
      be adapted to plan and endoscopically carry out the thoracoplasty. PURPOSE: To
      define the utility of 3-D CT volume rendering of the spine and thorax in the
      preoperative planning of endoscopic rib resection. STUDY DESIGN: A prospective
      evaluation of the utility of 3-D CT volume rendering for preoperative planning in
      patients with scoliosis undergoing endoscopic thoracoplasty for correction of rib
      humps. PATIENT SAMPLE: Four consecutive patients with previously fused scoliotic
      spines and pronounced right-sided rib humps requiring operative correction were
      selected. OUTCOME MEASURES: Outcome was assessed at a minimum follow-up of 6
      months by clinical examination, patient satisfaction with the clinical result,
      and repeat helical CT scanning with 3-D reconstruction. METHODS: Four patients
      with previously fused scoliotic spines and pronounced rib humps underwent helical
      CT scanning with 3-D volume rendering, prior to endoscopic corrective surgery.
      All four patients had right-sided rib humps requiring corrective rib resection
      for cosmetic reasons. Using the technique of 3-D volume rendering, a vector plane
      was created to mirror the left scapula, and its intersections on the right chest
      wall were noted. The ribs to be resected were marked, and the length of rib
      resection was measured from the vector plane's intersection points with the ribs.
      In this way an estimate of the resection required to achieve the desired final
      position of the right elevated scapula could be determined. Entry portals were
      also estimated with vector lines to achieve optimal access to each rib. During
      surgery, the portal sites were assessed for access to the selected ribs. Also,
      the extent of rib resections was compared with the estimates. The final clinical
      outcome was assessed by clinical examination, patient satisfaction with the
      cosmetic result, and repeat helical CT scanning with 3-D reconstruction. RESULTS:
      The male to female ratio was 1:3, and the average age was 21 years. Our average
      estimated blood loss was 307 ml and average hospital stay was 4.75 days. The
      estimated portal sites were accurate and did provide for direct access to each
      selected rib involved in the deformity. We were able to resect the ribs at the
      points suggested by 3-D CT volume rendering, with the lengths of our resected
      segments matching our preoperative estimates. In all cases the elevated right
      scapula did descend into the rib resection bed, thus balancing the shoulder
      heights. An excellent cosmetic result was achieved in all cases as evaluated by
      clinical examination, patient's perception, and repeat helical CT scanning.
      CONCLUSION: The technique of 3-D CT volume rendering with vector plane estimates
      provides a reliable estimate of the rib resection required to achieve a
      cosmetically acceptable correction of the rib hump through minimally invasive
      techniques.

PMID- 14588295
TI  - In vivo evaluation of calcium sulfate as a bone graft substitute for lumbar
      spinal fusion.
AB  - BACKGROUND CONTEXT: Posterolateral fusions of the lumbar spine have nonunion
      rates as high as 35%. The availability of autologous bone to promote fusion is
      limited, particularly for multilevel fusions. Bone substitutes have been proposed
      to augment or replace autologous bone for spinal surgery. Calcium sulfate offers
      high porosity, osteoconductivity, and high resorption rate. This material has
      been used successfully for treatment of long bone defects but has not been
      investigated as a bone graft substitute for spinal fusions. PURPOSE: To determine
      whether the use of calcium sulfate granules in conjunction with an implantable
      electrical stimulator is a safe and effective means of attaining spinal fusion.
      STUDY DESIGN/SETTING: A rabbit lumbar fusion model was used to assess a calcium
      sulfate bone graft substitute in combination with electrical stimulation for
      spinal fusion. METHODS: Thirty-six adult New Zealand White female rabbits were
      divided into three groups. Each group underwent a single-level (L5-L6) fusion,
      receiving 3.0 cc calcium sulfate granules with bone marrow aspirate from the
      iliac crest. Group 1 had no electrical stimulator applied. Groups 2 and 3
      received a 40-microA (Group 2) or a 100-microA (Group 3) implantable electrical
      stimulator. The animals were sacrificed at 8 weeks, and the rabbit spines were
      subjected to radiographic assessment, manual palpation, and mechanical testing.
      RESULTS: Two rabbits died postoperatively. The radiographic assessment revealed
      no fusions occurred at the adjacent nonoperated control levels (L4-L5). There
      were no fusions observed within Group 1, containing the calcium sulfate and bone
      marrow aspirate alone. The sites with the implantable stimulators showed a dose
      dependent increase in fusion stiffness. However, no fusion mass in Group 2 or 3
      was graded as bilaterally complete. CONCLUSION: This study found that calcium
      sulfate as a bone graft substitute was unsuccessful in promoting spine fusion in
      a rabbit model. There was radiographic evidence of rapid resorption of the
      calcium sulfate within 4 weeks after surgery. The use of electrical stimulation
      created a dose-dependent increase in mechanical competence of the bony mass.
      However, the addition of direct current (DC) current did not significantly alter
      fusion rates with calcium sulfate used as the bone graft substitute in this
      model.

PMID- 14588296
TI  - Influence of bone mineral density on pedicle screw fixation: a study of pedicle
      screw fixation augmenting posterior lumbar interbody fusion in elderly patients.
AB  - BACKGROUND CONTEXT: Some biomechanical studies have demonstrated that bone
      mineral density of the lumbar spine (BMD) affects the stability of pedicle screws
      in vitro. PURPOSE: To investigate influence of BMD on loosening and related
      failure of pedicle screws in vivo. STUDY DESIGN/SETTING: A clinical study of 52
      patients who underwent pedicle screw fixation augmenting posterior lumbar
      interbody fusion (PLIF). PATIENT SAMPLE: There were 13 men and 39 women, with an
      average age of 63 years (range, 45-76 years) at the time of operation. The mean
      follow-up period was 2.8 years (range, 2-6 years). OUTCOME MEASURES: Relationship
      between BMD, screw loosening, and its related failures were statistically
      analyzed. METHODS: BMD was measured by the dual energy X-ray absorptiometry
      (DEXA) method. Radiographic assessments were done by the first author and
      independently by another orthopedist who was not informed of the values of BMD.
      RESULTS: The mean BMD of all patients was 0.879 +/- 0.215 (mean +/- S.D.) g/cm2.
      The mean BMD in patients with and without screw loosening was 0.720 +/- 0.078
      g/cm2 (n=11) and 0.922 +/- 0.221 g/cm2 (n=41). There was a significant difference
      between the mean BMD of patients with and without screw loosening (P<.01). The
      mean BMD of patients with "union," "nonunion" and "undetermined union" was 0.934
      +/- 0.210 g/cm2 (n=40), 0.674 +/- 0.104 g/cm2 (n=4) and 0.710 +/- 0.116 g/cm2
      (n=8), respectively. The mean BMD of patients with "union" was significantly
      greater than those with "nonunion" and "undetermined union" (P<.05). CONCLUSION:
      It could be concluded that BMD has a close relation with the stability of pedicle
      screws in vivo, and BMD value below 0.674 +/- 0.104 g/cm2 suggests a potential
      increased risk of "nonunion" when pedicle screw fixation is performed in
      conjunction with PLIF.

PMID- 14588297
TI  - Characteristics of pullout failure in conical and cylindrical pedicle screws
      after full insertion and back-out.
AB  - BACKGROUND CONTEXT: Biomechanical studies show that bone-mineral density, pedicle
      morphology, and screw thread area affect pedicle screw pullout failure. The
      current literature is based on studies of cylindrical pedicle screw designs.
      Conical screws have been introduced that may provide better "fit and fill" of the
      dorsal pedicle as well as improved resistance to screw bending failure. However,
      there is concern about loss of fixation if conical screws must be backed out
      after insertion. PURPOSE: To determine that conical screws have comparable
      initial stiffness and fixation strength compared with standard, cylindrical
      screws, and to assess whether conical screw fixation deteriorates when screws are
      backed out from full insertion. STUDY DESIGN/SETTING: This biomechanical analysis
      compared pullout strength of cylindrical and conical pedicle screw designs, using
      porcine lumbar vertebrae in a paired testing format. METHODS: Porcine lumbar
      vertebrae were instrumented with conical and cylindrical pedicle screws with the
      same thread pitch, area and contour, and an equivalent diameter at the pedicle
      isthmus, 1.2 cm distal to the hub. Axial pullout was performed at 1.0 mm/minute
      displacement. Pullout loads, work and stiffness were recorded at 0.02-second
      intervals. Conical versus cylindrical screws were tested using three paired
      control configurations: fully inserted, backed out 180 degrees and backed out 360
      degrees. Fully inserted values were compared with each set of back-out values to
      determine relative loss of fixation strength. Screw pullout data were analyzed
      using a Student's t test. RESULTS: Pullout loads in these porcine specimens were
      comparable to data from healthy human vertebrae. Conical screws provided a 17%
      increase in the pullout strength compared with cylindrical screws (P<.10) and a
      50% increase in initial stiffness (P<.05) at full insertion. There was no loss in
      pullout strength, stiffness or work to failure when conical or cylindrical screws
      were backed out 180 or 360 degrees from full insertion. CONCLUSIONS: Conical
      screws offer improved initial fixation strength compared with cylindrical screws
      of the same size and thread design. Our results suggest that appropriately
      designed conical screws can be backed out 180 to 360 degrees for intraoperative
      adjustment without loss of pullout strength, stiffness or work to failure.
      Intraoperative adjustments of these specific conical screws less than 360 degrees
      should not affect initial fixation strength. These results may not hold true for
      screws with a smaller thread area or larger minor diameter.

PMID- 14588298
TI  - Speculum lumbar extraforaminal microdiscectomy.
AB  - BACKGROUND CONTEXT: Public interest, monetary pressures and improving diagnostic
      techniques have placed an increasing emphasis on minimalism in lumbar disc
      excision. Current techniques include microlumbar discectomy and minimally
      invasive spinal surgery. Both are good techniques but may be painful, require a
      hospital stay and/or are not widely used because of difficulty acquiring the
      necessary skills. The author therefore developed a less invasive microscopic
      technique that may be performed on a consistent outpatient basis with easily
      acquired skills. PURPOSE: The purpose of this study was to describe a variant of
      minimally invasive lumbar disc excision, while assessing the effects on a small
      group of patients. STUDY DESIGN: The treatment protocol was a prospective
      community hospital-based case study designed to evaluate a less invasive method
      of excising herniated lumbar discs residing in the canal, foraminal or far
      lateral space. PATIENT SAMPLE: This study is comprised of 50 patients with all
      anatomic forms of lumbar disc herniations, inside or outside the canal, at all
      levels except the lumbosacral joint. OUTCOME MEASURES: Clinical results were
      measured by return to work time, the criteria of MacNab and by Prolo et al.'s
      economic and functional criteria. METHODS: Selection criteria included adult
      patients with intractable low back and leg pain, plus an imaging study revealing
      a lumbar disc herniation consistent with the patient's clinical presentation.
      Mean patient age was 48 years. The male:female ratio was approximately 2:1. All
      patients failed at least 3 weeks of conservative therapy. Herniations occurred
      from the L2-3 space through L4-5, with 30 herniations being within and 20 outside
      the spinal canal. Both contained and extruded/sequestered herniations were
      treated. Excluded from the study were patients with herniations inside the spinal
      canal at the L5-S1 level. Surgical approach was by microscopic speculum
      transforaminal route for discs residing both within and outside the lumbar canal.
      RESULTS: The initial 50 consecutive patients had successful technical operations
      performed on an outpatient basis by this less invasive technique. By the criteria
      of MacNab (Table 3), 84% (42 of 50) had an excellent or good result, returning to
      work at a mean time of 3.5 weeks. Per Prolo et al.'s economic scale, 72% were
      disabled at levels I and II before surgery. Postoperatively, 92% had improved to
      levels IV and V. Similarly, on his functional scale, 94% functioned at levels I
      and II before surgery, whereas 88% achieved levels IV and V after surgery. Eighty
      percent required no pain medications 1 week after surgery. The only complication
      was an L3 minor nerve root injury as it exited the L3-4 foramen. CONCLUSION: The
      author has described a minimally invasive technique for excising herniated discs
      that is applicable to all types of lumbar herniations, except for those residing
      in the canal at L5-S1. Clinical outcomes are comparable to those of other forms
      of discectomy.

PMID- 14588301
TI  - Regional and temporal changes in prostaglandin E2 and thromboxane B2
      concentrations after spinal cord injury.
AB  - BACKGROUND CONTEXT: Inflammatory metabolites of arachidonic acid likely play a
      significant role in secondary injury after spinal cord trauma. PURPOSE: We sought
      to characterize the regional and temporal alterations in prostaglandin
      concentrations after injury in a rat model. STUDY DESIGN/SETTING: Prostaglandin
      E2 (PGE2) and thromboxane B2 (TxB2) concentrations were measured in cerebrospinal
      fluid (CSF) and in different parts of the injured spinal cord at various time
      points after spinal cord injury. OUTCOME MEASURES: PGE2 and TxB2 levels were
      measured by means of an enzyme immune assay. METHODS: Forty-six adult Long Evans
      rats were subject to spinal cord injury using the NYU impactor. Animals were
      divided into three groups. Fourteen animals were used in a pilot study to
      determine the timing and location of PGE2 production after spinal cord injury.
      These animals were sacrificed, and samples of injured cord, rostral cord and CSF
      were assayed for PGE2 concentration. The remaining 32 animals were used to
      establish the time course of prostaglandin production. Twenty-eight animals were
      subjected to a spinal cord injury, and four animals served as sham-operated
      controls. These animals were sacrificed at predetermined time points 2 to 72
      hours after injury, and the injured segments of spinal cord were harvested.
      RESULTS: Both PGE2 and TxB2 concentrations increased immediately after injury in
      the injured segment. PGE2 concentrations increased faster and more dramatically
      in the injured segment of spinal cord than in CSF or noninjured segments.
      Elevations in PGE2 and TxB2 concentrations were persistent for 72 hours after
      injury. CONCLUSION: Elevated concentrations of arachidonic acid metabolites can
      be detected in the injured segment of the spinal cord for at least 72 hours after
      injury. Concentration changes are detected earlier and are more dramatic in the
      injured cord segment than in rostral segments or the CSF.

PMID- 14588300
TI  - Electron microscopic observation of established chondrocytes derived from human
      intervertebral disc hernia (KTN-1) and role of macrophages in spontaneous
      regression of degenerated tissues.
AB  - BACKGROUND CONTEXT: Biological and pathological cell processes during the
      degeneration of intervertebral discs are as yet poorly understood. PURPOSE: An
      electron microscope was used to observe disc hernia degeneration at the cellular
      level as expressed in extruded tissue from a human intervertebral disc and in
      cultured chondrocytes. The mechanism of spontaneous regression was analyzed in
      order to investigate the effects of homologous macrophages, and the results of
      this analysis may be developed into a clinical therapy. STUDY DESIGN/SETTING:
      Extruded tissue specimens excised during surgery on human intervertebral disc
      hernia and cultured chondrocytes isolated from the excised tissue were observed
      by means of electron microscopy. Extracellular matrix metalloproteinase-3 (MMP-3)
      and its antagonist, tissue inhibitor of metalloproteinases-1 (TIMP-1), were
      observed by means of immune electron microscopy. Macrophages confirmed by CD68
      immunostaining were added to the chondrocyte culture and observed by means of
      electron microscopy. PATIENT SAMPLE: All control subjects and patients gave
      written consent to the study. OUTCOME MEASURES: KTN-1 was directly observed
      without culture, and nuclei degeneration, the development of chromatin granules,
      changes in the osmotic pressure of the nuclear membrane and rough-surfaced
      endoplasmic reticulum, and the development of fat droplets were observed.
      METHODS: Tissues excised during surgery were divided, a part of the tissues were
      fixed in various fixatives for electron microscopy and immune electron microscopy
      analysis, and the other part was treated with collagenase. In addition,
      chondrocytes were isolated and cultured. Human peripheral blood mononuclear cells
      were separated using the Ficoll method. After culturing the cells, macrophages
      were collected, added to the chondrocyte culture, and observed under an electron
      microscope. CD68 positivity of the macrophages was confirmed by CD68
      immunostaining. RESULTS: Freshly isolated chondrocytes in the hernia's extruded
      region differed markedly from cultured chondrocytes. By means of immunoelectron
      microscopy, MMP-3 and TIMP-1 were localized at the endoplasmic reticulum of the
      cultured chondrocytes. Infiltration of macrophages among the chondrocytes was
      observed in the mixed culture. CONCLUSIONS: The tissue extruded from the
      intervertebral disc showed obvious signs of degeneration, such as changes in
      osmotic pressure. Macrophages were observed to be the mechanism of spontaneous
      regression.

PMID- 14588302
TI  - Selective cyclooxygenase 2 inhibition lowers spinal cord prostaglandin
      concentrations after injury.
AB  - BACKGROUND CONTEXT: Prostaglandin E2 (PGE2) and thromboxane B2 (TxB2)
      concentrations are elevated in the injured spinal cord for hours to days after
      injury. Treatment of animals with a selective cyclooxygenase-2 (COX-2) inhibitor
      has been shown to improve functional outcome in an animal model. PURPOSE: We
      sought to characterize the effects of COX-2 inhibition on prostaglandin
      concentrations in the spinal cord after injury. STUDY DESIGN/SETTING: A drug
      study was performed using 76 male Long Evans rats. OUTCOME MEASURES: PGE2 and
      TxB2 concentrations were measured by enzyme immune assay. METHODS: Fifty-six rats
      were subject to spinal cord injury, and 4 rats served as sham controls. Twenty
      eight rats received 3 mg/kg of celebocid by means of an orogastric tube within 20
      minutes after injury, and 28 received vehicle alone. The animals were sacrificed
      at time points between 2 and 72 hours after injury, and PGE2 and TxB2 levels were
      measured. A second study was performed using transcardiac saline perfusion in
      order to reduce intragroup variance in measured PGE2 and TxB2 levels. Sixteen
      animals underwent spinal cord injury. Animals were sacrificed at 4 and 24 hours
      after injury, and PGE2 and TxB2 levels were measured. RESULTS: PGE2 and TxB2
      concentrations were elevated after injury in all animals. Administration of
      celebocid resulted in a delayed reduction of PGE2 and TxB2 concentrations in the
      initial drug study. These results were not statistically significant.
      Transcardiac perfusion with normal saline reduced the intragroup variance. Using
      this technique, administration of celebocid resulted in a statistically
      significant reduction in PGE2 and TxB2 concentrations in the injured cord segment
      4 and 24 hours after injury. CONCLUSION: Administration of a selective COX-2
      inhibitor after injury results in a decrease of PGE2 and TxB2 concentrations in
      the injured spinal cord. Transcardiac perfusion after sacrifice reduces measured
      variance, probably through reducing the contribution of blood-borne
      prostaglandins.

PMID- 14588304
TI  - The proper use of the word "nonoperative" as opposed to "conservative".

PMID- 14588303
TI  - Vascular anatomy anterior to lumbosacral transitional vertebrae and implications
      for anterior lumbar interbody fusion.
AB  - BACKGROUND CONTEXT: Anterior approaches to the lumbosacral spine afford the ideal
      window to the disc for interbody fusion. Vascular injuries represent the most
      feared complications of such approaches. Unfortunately, the combination of more
      procedures being performed, more surgeons at the beginning of the learning curve
      and less invasive techniques of approach combine to increase the risk of vascular
      injury in the face of altered vascular anatomy. PURPOSE: To assess cases in which
      vascular anatomy significantly altered the surgical approach to the lumbosacral
      junction. STUDY DESIGN/SETTING: Chart review of operative reports. PATIENT
      SAMPLE: All patients undergoing anterior lumbar interbody fusion between 1994 and
      1997 at one large center. METHODS: We reviewed all cases of anterior lumbar
      interbody fusion performed between 1994 and 1997 to discover cases requiring
      significant alteration in approach because of vascular variation. RESULTS: One
      hundred seven consecutive cases were reviewed. Of these, 11 required significant
      alteration of the approach secondary to vascular variation. All 11 were in cases
      at the functional lumbosacral junction above a fixed transitional level. In only
      one case of transition was a usual approach able to be used. CONCLUSIONS: A
      consistent pattern of altered vascular anatomy anterior to the functional
      lumbosacral junction was found. This pattern is depicted and the surgical
      alterations required discussed. Such alteration in surgical approach was required
      in nearly all cases with transitional vertebrae and represented about 10% of
      cases overall. If anterior lumbar surgery is to be performed at the functional
      lumbosacral junction in the presence of transitional vertebrae, it is vital that
      close attention be paid to the vascular anatomy and more open techniques of
      approach should be considered.

PMID- 14588306
TI  - Assisting patients in their choice of treatment options: a primary goal of all
      spine care clinicians.

PMID- 14588307
TI  - Segmental instrumentation for thoracic and thoracolumbar fractures: prospective
      analysis of construct survival and five-year follow-up.
AB  - BACKGROUND CONTEXT: Segmental instrumentation systems have replaced nonsegmental
      systems in all areas of spine surgery. Construct patterns for fracture
      stabilization have been adapted from deformity experience and from biomechanical
      studies using nonsegmental systems. Few studies have been completed to validate
      the use of these implants in trauma or to assess their relative strengths and
      weaknesses. PURPOSE: To substantiate the safety and efficacy of segmental spinal
      instrumentation used to treat patients with unstable spinal fractures and to
      identify successful construct strategies and potential pitfalls. STUDY DESIGN: A
      prospective, longitudinal single cohort study of patients treated with segmental
      instrumentation for fractures of the spine. Minimum 2-year follow-up. PATIENT
      SAMPLE: Seventy-five consecutive patients with unstable fractures of the
      thoracic, thoracolumbar and lumbar vertebrae, admitted to a level 1 trauma
      center. All patients sustained high-energy injuries: fifty-five (79%) were
      injured in motor vehicle accidents, 27 (38%) sustained two or more major
      additional injuries and 39 (56%) had neurological injuries. OUTCOME MEASURES:
      Perioperative morbidity and mortality, blood loss, surgical time; postoperative
      recovery, neurological recovery, complications, thromboembolic and pulmonary
      disease; long-term outcome measures of fusion, sagittal spinal alignment,
      construct survival, patient pain and function measures, and return to work and
      activity. METHODS: A longitudinal, prospective study of surgical outcome after
      segmental spinal instrumentation. Multifactorial assessment was carried out at
      prescribed intervals to a mean follow-up of 5 years (range, 2 to 8 years) from
      the time of surgery. Seventy patients were included in the final analysis. There
      were 17 thoracic, 36 thoracolumbar and 17 lumbar fractures. RESULTS: At 52 months
      mean follow-up, 57 of 62 patients (92%) had solid fusion with acceptable spinal
      alignment. Perioperative complications and mortality were less than expected,
      based on historical controls matched for injury severity. Rod and hook constructs
      had 97% good to excellent functional results, with no hardware complications. Six
      of 11 (55%) patients with short-segment pedicle instrumentation (SSPI) with no
      anterior column reconstruction had greater than 10 degrees of sagittal collapse
      during the fracture healing period. Twenty six of 36 neurologically injured
      patients (72%) experienced (mean) 1.5 Frankel grades recovery after decompression
      and stabilization. Residual neurological deficit determined return to work: 43
      patients (70%) returned to work, 33 without restrictions, 10 with limitations.
      Five other patients (8%) were fit but unemployed. Fifteen percent experienced
      some form of hardware failure, but only three (5%) required revision. Hardware
      complications and fair to poor outcomes occurred after pedicle instrumentation
      without anterior reconstruction. Patients with anterior reconstruction had 100%
      construct survival, no sagittal deformity, and less pain. CONCLUSION: Segmental
      instrumentation allowed immediate mobilization of these severely injured
      patients, eliminating thromboembolic and pulmonary complications, and reducing
      overall morbidity and mortality. Segmental instrumentation produced a high rate
      of fusion with no rod breakage or hook failure. Pedicle screw constructs had a
      high rate of screw complications associated with anterior column insufficiency,
      but revision was not always necessary. Eighty percent of these severely injured
      patients were capable of returning to full-time employment, and 70% did so.

PMID- 14588309
TI  - The inverse effects of load transfer and load sharing on axial compressive
      stiffness.
AB  - BACKGROUND CONTEXT: The goal of spinal instrumentation is to stabilize involved
      motion segments while fusion occurs. Although some degree of load sharing is
      necessary for fusion, the ability of the instrumentation system to transfer the
      load may vary. PURPOSE: The purpose of this study is to formulate a mathematical
      relationship between load sharing and load transfer of specific spinal
      instrumentation systems using a well-accepted mechanical model. STUDY
      DESIGN/SETTING: Forty-eight American Society for Testing Materials standard ultra
      high molecular weight polyethylene cylinders were used as per designation F 1717
      96, standard test methods for static and fatigue for spinal implant constructs in
      a corpectomy model. METHODS: Twenty-four spinal assemblies consisting of anterior
      plates, anterior rod, and posterior rods were subjected to compression bending
      tests using a MTS Bionix servo-hydraulic material testing apparatus. Each implant
      was tested in compression bending with and without the addition of a titanium
      load-sharing cage. The force applied was the independent variable, and the
      displacement was the dependent variable. The stiffness was determined for each
      setup with and without the addition of an anterior load-sharing cage. RESULTS:
      The average axial compressive stiffness of a system increased by a factor of 8.5
      with the addition of the load-sharing cage. An inverse relationship existed
      between the compressive stiffness of the construct and its relative increase
      achieved with the addition of the load-sharing cage. The compressive stiffness of
      the system with the addition of the load-sharing cage approached that of the
      anterior device itself as the system flexibility increased. The ability of
      instrumentation systems to load share or load transfer and their respective
      stiffness was determined. CONCLUSIONS: The 5-mm rod screw posterior system was
      compared with the 7-mm Ti posterior system with the addition of one and two
      devices for transverse traction (DTTs). The rods with the increased diameter had
      a stiffness of 1723 n/mm with one DTT and 1815 n/mm with two DTTs. The addition
      of an anterior cage had little effect on the stiffness of these systems. Anterior
      plate and screw/rod systems were analyzed and showed similar mechanical behavior
      to the 5-mm posterior rod/screw systems. A significant increase in stiffness was
      realized with the addition of an anterior cage. A means to determine the load
      sharing/transferring properties of a spinal instrumentation system is presented.
      This technique will allow the amount of load transferred from the fusion mass to
      the instrumentation to be predicted.

PMID- 14588311
TI  - Anterior cervical interbody fusion with rhBMP-2 and tantalum in a goat model.
AB  - BACKGROUND CONTEXT: Tricortical autogenous iliac crest has long served as the
      gold standard for arthrodesis after cervical discectomy. The added morbidity
      resulting from bone graft harvest may be eliminated by the use of a biocompatible
      synthetic bone graft substitute with osteoconductive abilities, and when used
      with an osteoinductive agent, such as recombinant bone morphogenic protein
      (rhBMP)-2, it may facilitate arthrodesis similar to autograft. PURPOSE: To
      determine by radiographic and histologic analysis whether tantalum with and
      without rhBMP-2 can facilitate bony ingrowth and arthrodesis in an animal model.
      STUDY DESIGN/SETTING: Single-level anterior cervical discectomy and fusion was
      performed using a tantalum bone graft substitute with and without rhBMP-2 in a
      previously established goat model for anterior cervical fusion. METHODS: Eight
      goats underwent single-level anterior cervical discectomy and stabilization with
      a porous tantalum implant. There were four goats in each experimental group.
      Group A underwent anterior cervical stabilization with tantalum alone, whereas in
      Group B rhBMP-2 was added to the tantalum implant. The goats were sacrificed at
      12 weeks, and their cervical spines were removed for histologic and radiological
      analysis. RESULTS: Only one of four goats in Group A had any bony ingrowth into
      the tantalum. Three of four goats in Group B demonstrated bony ingrowth. The
      average extent of bony ingrowth at the perimeter of the tantalum in Group A was
      2.5% compared with 12.5% in Group B. Similarly, the volume of bony ingrowth
      within the tantalum was 2.5% in Group A and 10% in Group B. The difference was
      not statistically significant. CONCLUSIONS: The data in this pilot study suggest
      that tantalum may function as a synthetic osteoconductive bone graft substitute.
      The addition of rhBMP-2 may facilitate osteoinduction within a synthetic
      osteoconductive implant. The sample size in this study was too small for
      statistical significance. The present animal model as used in this study was
      inadequate for cervical arthrodesis where rigid implant fixation is desired.

PMID- 14588312
TI  - The effect of varied electrical current densities on lumbar spinal fusions in
      dogs.
AB  - BACKGROUND CONTEXT: The use of electrical stimulation has been shown to increase
      the rate of successful spinal fusions. It is possible that increasing the current
      density of these stimulators may increase the speed and success rate of these
      fusions. PURPOSE: This study evaluated the effects of varied current densities on
      the speed and success rate of spinal fusion in dogs. STUDY DESIGN/SETTING: Three
      different current densities (0.83 microA/cm, 4 microA/cm and 10 microA/cm) were
      used to stimulate spinal fusions in a canine model over a 12-week period. OUTCOME
      MEASURES: Radiographic and histologic assessments were used to determine the
      degree of facet fusions at each time period. METHODS: Fifteen dogs underwent
      spinal facet fusion bilaterally at the level of L1-2 and L4-5. Each fusion site
      was electrically stimulated using one of three current densities. At 6, 9 and 12
      weeks, the specimens were evaluated using high-resolution radiography and routine
      histology. The fusion masses were graded and then statistically evaluated.
      RESULTS: The results demonstrate a dose response of fusion mass scores to
      increasing current density. The highest current density (10 microA/cm)
      demonstrated a statistically higher fusion scores than the lowest currently
      density (0.83 microA/cm) at 6 weeks and statistically greater than both the
      middle (4 microA/cm) and lowest (0.83 microA/cm) current densities at 9 weeks. No
      differences were noted at 12 weeks, because all groups showed complete fusion.
      CONCLUSIONS: This controlled study suggests that speed of fusion may be further
      improved by increasing the current density of the electrical stimulation.

PMID- 14588316
TI  - Patient satisfaction with spinal cord stimulation for predominant complaints of
      chronic, intractable low back pain.
AB  - BACKGROUND CONTEXT: Results of subsequent surgical intervention in patients with
      intractable pain after lumbar spine surgery are typically worse than for initial
      surgery, particularly in those with predominant complaints of back pain rather
      than lower extremity pain. Spinal cord stimulation (SCS) has been found to yield
      good results in patients with primary complaints of intractable lower extremity
      pain. Technological advances have broadened the indications for this treatment.
      PURPOSE: The purpose of this study was to evaluate patient satisfaction after SCS
      in the treatment of patients with predominant complaints of chronic, intractable,
      low back pain. STUDY DESIGN/SETTING: Data were collected from retrospective chart
      review and patient follow-up questionnaire. Patients were treated at a spine
      specialty center. PATIENT SAMPLE: The study group consisted of the consecutive
      series of our first 41 patients who underwent SCS for predominant complaints of
      low back pain. The mean symptom duration was 82.9 months, and the mean age was
      47.9 years (range, 28-83 years). All but three patients had previously undergone
      lumbar spine surgery (mean, 2.3 prior surgeries). OUTCOME MEASURES: At the time
      of follow-up (5.5-19 months after SCS implantation), patients completed
      questionnaires assessing their satisfaction with their outcome, if they would
      have the procedure again knowing what their outcome would be and if they would
      recommend SCS to someone with similar problems. In determining outcome, a
      negative response was assigned for patients who had the device removed. A worst
      case analysis was also conducted in which a negative response was assigned for
      patients lost to follow-up or who failed to respond to a particular question.
      Data were also collected on complications and re-operations. METHODS: All trial
      stimulation procedures were performed under local anesthetic with the patient
      providing feedback concerning pain relief achieved with various lead placements
      and settings. If one lead did not provide acceptable relief in all the areas
      needed, placement of a second lead was pursued. If the patient failed to maintain
      acceptable pain relief (> or =50% pain relief) during a multiday trial period,
      the leads were removed. If adequate relief was maintained during the trial
      period, the receiver was implanted. RESULTS: Responses to the follow-up
      questionnaire indicated that 60% of patients considered themselves improved from
      their preoperative condition and the remaining 40% did not; 78.1% of patients
      would recommend SCS to someone with similar problems, 69.0% were satisfied, 75.0%
      would have the procedure performed again if they had known their outcome before
      implantation. Among the 36 patients in whom the system was implanted, it was
      later removed in 4 because of lack of sufficient pain relief. Other re-operations
      included repositioning of the leads to regain pain relief in the areas needed,
      replacement of a malfunctioning unit and revision of lead extension wires.
      CONCLUSIONS: In this retrospective study, the majority of patients were satisfied
      with the results of SCS and would have the procedure again knowing what their
      outcome would be. These results suggest that further investigation of SCS is
      warranted in this difficult to treat patient population presenting with
      predominant complaints of chronic, intractable, axial low back pain.

PMID- 14588314
TI  - Anterior cervical fusion using porous hydroxyapatite ceramics for cervical disc
      herniation. a two-year follow-up.
AB  - BACKGROUND CONTEXT: The Smith-Robinson Method (SR), which employs autogenous
      bone, is the current standard for anterior cervical fusion (AF) surgery. However,
      autogenous bone has graft-related complications and morbidity, and harvesting it
      increases trauma and risk to the patient. The use of hydroxyapatite ceramic (HAP)
      inserts may provide a superior alternative. PURPOSE: To determine the efficacy of
      using HAP in AF. STUDY DESIGN/SETTING: A retrospective study of patients who had
      AF surgery with wide decompression and porous HAP inserts used to treat cervical
      disc herniation (CHD). PATIENT SAMPLE: We evaluated 36 patients who had single
      level AF using HAP for CHD, without internal fixations, clinically and
      radiographically with a minimum follow-up of 2 years. There were 25 men and 11
      women, with an average age of 49 years (age range, 24-78 years). Preoperative
      diagnosis included 25 cases with myelopathy and 11 cases with radiculopathy.
      OUTCOME MEASURES: We established four grades to classify the degree of bony
      fusion between the HAP and vertebra, based on any motion at the fused segment,
      any radiolucent zones (RZ) between vertebral bodies and the grafted HAP, and
      anterior or posterior bone formations on grafted HAPs. We evaluated the severity
      of myelopathy by applying the Japan Orthopaedic Association (JOA) scoring system.
      We evaluated the surgical outcome of the myelopathy patients using the
      Hirabayashi recovery rating, and for the radiculopathy patients, we used the
      Herkowitz criteria. METHODS: We retrospectively reviewed the radiographic and
      clinical records of all 36 patients from surgery up to periods ranging from 2 to
      7 years after surgery, with the average period of follow-up being 4.5 years. We
      systematically classified the degree of bony fusion into four grades ranging from
      Grade 1 nonunion to Grade 4 complete union. RESULTS: None of the subjects showed
      Grades 1 and 2 fusion. Eleven percent of the cases showed Grade 3 and 89% showed
      Grade 4. Loss of height of the fused segment was observed in 29 cases with an
      average of 1.6 mm. A decrease of lordotic angle of the fused segment was observed
      in six cases with an average of 2.3 degrees. Four cases revealed cracked HAP
      inserts but achieved Grade 4 bone fusion. There was no evidence of collapse or
      displacement of HAPs. The results of the 11 radiculopathy patients were excellent
      in 10 cases and good in the remaining case. The recovery rate of the 25
      myelopathy patients was 73.0%. CONCLUSIONS: Our method of anterior cervical
      fusion surgery using porous HAP inserted into resected end plates, combined with
      a wide decompression procedure, had clinical and radiographic results so
      satisfactory that we conclude that it can effectively replace the use of
      autogenous bone for treating cervical disc herniation.

PMID- 14588317
TI  - Discography. a review.
AB  - BACKGROUND CONTEXT: Discography is used today as the basis of the diagnosis of
      discogenic back and neck pain. As such, it plays a pivotal role in the
      formulation of treatment plans for patients complaining of chronic axial spine
      pain. PURPOSE: A brief history of discography is described here, followed by a
      discussion of the current uses of discography, the technique involved, and recent
      studies questioning its validity. STUDY DESIGN/SETTING: A selective review of
      discography articles from peer-reviewed literature from 1967 to 2000 is provided.
      We included articles analyzing the validity of discography as well as those
      concerning its proper use, technique, and complications. METHODS: Articles
      relevant to the subject of discography were systematically reviewed for
      recommendations regarding technique, the interpretation of results, and
      conclusions regarding its validity. RESULTS: The specificity of discography is
      dramatically affected by the characteristics of the patient examined. In a
      patient with chronic pain states and psychiatric risk factors, the specificity
      was determined to be at most 20%. In healthy patients with no chronic pain states
      and a normal psychiatric profile, the specificity was found to be at most 90%.
      The ability of a patient to determine reliably the concordance of pain provoked
      during discography is poor. We could find no data addressing the sensitivity of
      the study. CONCLUSIONS: Clinicians who use discography to determine treatment
      pathways for their patients need to critically examine the validity of the test.
      Recent studies examining the specificity of discography have led us to proceed
      much more cautiously in interpreting the results of discography.

PMID- 14588318
TI  - Segmental pedicle screw fixation or cross-links in multilevel lumbar constructs.
      a biomechanical analysis.
AB  - BACKGROUND CONTEXT: The placement of segmental pedicle screws and cross-links in
      short segment posterior pedicle screw constructs has been shown to increase the
      construct stiffness in some planes. To date, no studies have looked at the
      contributions of segmental pedicle screw and cross-link placement in longer
      constructs. PURPOSE: To evaluate the influence of segmental pedicle screw and/or
      cross-link placement on flexion/extension, lateral bending and axial torsion
      stiffness in two- and three-level posterior pedicle screw fixation constructs.
      STUDY DESIGN/SETTING: An in vitro biomechanical analysis of two- and three-level
      posterior pedicle screw constructs with and without segmental fixation and/or
      cross-links was performed using calf lumbar spines. Stiffness of the constructs
      was compared. METHODS: Six calf lumbar specimens were used to test stiffness in
      one-, two- and three-level posterior pedicle screw fixation constructs in 12
      configurations. A custom-made, four-axis spine simulator applied pure cyclical
      (+/-5 Nm) flexion/extension, lateral bending and axial torsion moments at 0.1 Hz
      under a constant 50-N axial compressive load. The stiffness of each construct was
      calculated about each axis of rotation. Data were analyzed using nonparametric
      techniques with statistical significance determined at alpha less than .05.
      RESULTS: The stiffness of the instrumented spines were significantly greater than
      the noninstrumented intact spines in all loading conditions for one-, two- and
      three-level constructs. There were no significant changes in flexion/extension
      stiffness with the addition of either the cross-links or the segmental pedicle
      screws. In lateral bending, the addition of segmental pedicle screws
      significantly increased the stiffness in the two- and three-level constructs. The
      addition of two cross-links increased lateral bending stiffness in the longer
      three-level constructs, with little change in the two-level constructs. In axial
      torsion, the progressive addition of cross-links showed a tendency toward
      increased stiffness in both the two- and three-level constructs. Segmental
      pedicle screws further increased torsional stiffness of the longer, three-level
      constructs. CONCLUSIONS: As the use of segmental spinal instrumentation
      progresses from one to two and three levels, the contribution of cross-links and
      segmental pedicle screws to the overall construct stiffness increases.

PMID- 14588320
TI  - Spine and the law.

PMID- 14588321
TI  - Arts and spine. The bellringer's kyphosis.

PMID- 14588322
TI  - Spine stats. The Cox regression analysis.

PMID- 14588323
TI  - Faces of spine care: from the Imaging Department.

PMID- 14588326
TI  - Is there room for another point of view?

PMID- 14588327
TI  - The effect of static in vivo bending on the murine intervertebral disc.
AB  - BACKGROUND CONTEXT: Intervertebral disc cell function in vitro has been linked to
      features of the local environment that can be related to deformation of the
      extracellular matrix. Epidemiologic data suggest that certain regimens of spinal
      loading accelerate disc degeneration in vivo. Yet, the direct association between
      disc cell function, spinal loading and ultimately tissue degeneration is poorly
      characterized. PURPOSE: To examine the relationships between tensile and
      compressive matrix strains, cell activity and annular degradation. STUDY
      DESIGN/SETTING: An in vivo study of the biologic, morphologic and biomechanical
      consequences of static bending applied to the murine intervertebral disc. SUBJECT
      SAMPLE: Twenty-five skeletally mature Swiss Webster mice (12-week-old males) were
      used in this study. OUTCOME MEASURES: Bending neutral zone, bending stiffness,
      yield point in bending, number of apoptotic cells, annular matrix organization,
      cell shape, aggrecan gene expression, and collagen II gene expression. METHODS:
      Mouse tail discs were loaded for 1 week in vivo with an external device that
      applied bending stresses. Mid-sagittal sections of the discs were analyzed for
      cell death, collagen II and aggrecan gene expression, and tissue organization.
      Biomechanical testing was also performed to measure the bending stiffness and
      strength. RESULTS: Forceful disc bending induced increased cell death, decreased
      aggrecan gene expression and decreased tissue organization preferentially on the
      concave side. By contrast, collagen II gene expression was symmetrically reduced.
      Asymmetric loading did not alter bending mechanical behavior of the discs.
      CONCLUSIONS: In this model, annular cell death was related to excessive matrix
      compression (as opposed to tension). Collagen II gene expression was most
      negatively influenced by the static nature of the loading (immobilization),
      rather than the specific state of stress (tension or compression).

PMID- 14588328
TI  - Low-intensity pulsed ultrasound improves spinal fusion.
AB  - BACKGROUND CONTEXT: Increasing the incidence of solid bony fusion is a primary
      goal in spine surgery. Daily low-intensity pulsed ultrasound therapy has been
      shown to improve and accelerate the bone healing process. PURPOSE: The purpose of
      this study was to evaluate the efficacy of daily low-intensity pulsed ultrasound
      therapy to improve the rate and quality of spinal fusion. STUDY DESIGN: Canine
      fusion model prospective study. PATIENT SAMPLE: Fourteen adult male dogs were
      used. OUTCOME MEASURES: Radiographic grading of plain films, computed tomography
      (CT) and magnetic resonance imaging (MRI), gross palpation, torsional stiffness
      and histologic grading were used to determine the presence or absence of fusion.
      METHODS: Posterior noninstrumented bilateral fusions were evaluated at the L2-L3
      and L5-L6 levels. Treatment with low-intensity pulsed ultrasound for 20 minutes
      per day over the fusion site (stimulated) was compared with fusion sites that
      received no stimulation (nontreated controls) at 6 and 12 weeks after surgery.
      Plain film radiographs, CT and MRI, mechanical torsion testing and histologic
      examination were performed. RESULTS: At 6 weeks, ultrasound treated sites were
      more frequently fused compared with nontreated controls, although the difference
      in fusion rate was not statistically significant. At 12 weeks after surgery
      complete radiographic and histologic fusion occurred in 100% of ultrasound
      treated sites. In the nontreated control sites 78% had achieved complete
      radiographic fusion and 44% had complete histologic fusion. Compared with control
      sites, the histological and mechanical fusion rate was significantly greater in
      ultrasound-treated sites (P<.05) at 12 weeks. A statistically significant
      increase in mechanical stiffness in ultrasound-treated sites was also found at 12
      weeks after surgery. CONCLUSIONS: Low-intensity pulsed ultrasound therapy may be
      a useful means to ensure successful spine fusion.

PMID- 14588329
TI  - Physical characteristics of the axial interosseous ligament of the human
      sacroiliac joint.
AB  - BACKGROUND CONTEXT: Although the sacroiliac joint has occupied a place in medical
      literature since at least the eighteenth century, its role in normal function and
      dysfunction of the back and hip remains controversial. The controversy persists,
      because there is still no suitable method to study the role of stability and
      mobility at the sacroiliac joints in vivo. One cost-effective approach to
      understanding such complex, deeply placed structures is biomechanical modeling.
      Unfortunately, very few data on the mechanical properties of tissues in this
      region are currently available to modelers. PURPOSE: The objective of this
      preliminary project was to determine some mechanical properties of the axial
      interosseous ligament (AIL), and to investigate the histology of the ligament.
      STUDY DESIGN/SETTING: A modified split plot design was used in conjunction with
      descriptive statistics to identify AIL characteristics. PATIENT SAMPLE: This was
      a cadaveric study. OUTCOME MEASURES: The study used descriptive statistics to
      categorize the ultimate failure strength of the AIL, and to describe the macro
      constituents of the ligament. METHODS: Eighteen sacroiliac joints were harvested
      from nine fresh female cadavers (age range, 54 to 92). Data from 10 joints
      submitted to mechanical testing are reported. The eight remaining joints were
      used for histologic analysis of the AIL by light microscopy. RESULTS: The AIL
      proved to be relatively weak, with a mean failure load of 381 N (SD 43.7N) and a
      peak stress of 1.73 MPa (SD 0.99 MPa). Histologically, the AIL contained
      significantly less collagen than most other "typical" ligaments. CONCLUSIONS: The
      AIL failure loads are just slightly higher than those for the ligamentum flavum
      in the spine, a tissue composed mainly of elastic fibers. In contrast, the AIL
      has negligible elastin content. Because the AIL represents about 14% of the total
      area of interosseous sacroiliac ligaments, its mechanical properties should be
      useful to modelers of the joint. In addition, it appears that injury to the AIL
      would do little to compromise the mechanical integrity of the sacroiliac joint.
      Further study of this ligament seems warranted.

PMID- 14588330
TI  - Biocompatibility studies of titanium-based alloy pedicle screw and rod system:
      histological aspects.
AB  - BACKGROUND CONTEXT: Few histological studies of pedicle screw and rod systems
      have been done, and spinal surgery with pedicle screw and rod system is
      increasing. PURPOSE: To know the biocompatibility of pedicle screw and rod
      systems histologically. STUDY DESIGN/SETTING: Titanium-based alloy pedicle screws
      were removed from 20 patients. Histological studies of the tissue response to the
      screws were performed by light microscopy. PATIENT SAMPLE: Twenty patients, who
      were diagnosed with burst type spinal fracture, spondylolysis, spondylolisthesis,
      and lumbar disc herniation. OUTCOME MEASURES: All slides were observed by light
      microscopy, and inflammation, fibrous tissue formation, and wear debris were
      evaluated using a subjective scale. METHODS: Before the surgery, plain
      radiographs were taken to confirm the solid arthrodesis. Histological analysis
      was divided into four areas and studied using light microscopy. RESULTS:
      Inflammation and fibrous tissue formation were the main tissue reactions to the
      implants. No tissue surrounding the implants showed irreversible changes. Fibrous
      tissue was often observed at the bone-screw interface without direct contact of
      screw and bone at the muscle-screw interface histologically. Although some
      titanium debris was observed in both interfaces, no debris of inflammatory cells
      were seen at 1 cm distance from the screws. The inflammatory response to the
      screw debris was localized. CONCLUSIONS: Titanium-based alloy pedicle screws
      produced some metal debris and caused localized inflammation. No adverse tissue
      reaction was observed around the screws and rods. Direct contact without any
      fibrous tissue formation at the bone-screw interface was observed in some
      patients. A titanium-based alloy pedicle screw and rod system is considered
      biocompatible histologically.

PMID- 14588331
TI  - Conservative treatment for cervical spondylotic myelopathy. prediction of
      treatment effects by multivariate analysis.
AB  - BACKGROUND CONTEXT: Many studies have suggested only slight effects of
      conservative treatment on cervical spondylotic myelopathy (CSM), whereas a few
      reports describe conservative treatment as being effective. This suggested the
      influence of various factors on treatment outcomes. PURPOSE: We investigated
      symptomatic changes after conservative treatment in patients based on a clear
      understanding of the effects and limitations of conservative treatment. STUDY
      DESIGN: We have encountered cases that showed symptomatic improvement with
      conservative treatment and became interested in the effectiveness of conservative
      treatment for CSM and whether other factors affect the results of conservative
      treatment. PATIENT SAMPLE: We have analyzed the results of conservative treatment
      for CSM in 69 cases, derived from a population of 101 CSM cases. OUTCOME
      MEASURES: Symptoms at the time of the first examination were compared with those
      at the final examination, and the patients were classified into three groups
      showing improvement, no change or exacerbation. METHODS: Improvement or
      exacerbation of the symptoms was used as dependent variables and the collected
      factors as independent variables, and logistic regression was performed on these
      variables. RESULTS: Multivariate analysis showed significant correlation between
      clinical outcome and the disease duration and the presence of rigorous
      conservative treatment. CONCLUSIONS: Conservative treatment for CSM is considered
      to be effective if it is performed intensively in selected patients. In treating
      CSM, the therapeutic approach must be selected first in consideration of the
      patient's disease duration. Conservative treatment must be carried out
      intensively after sufficient explanation to the patients. Timely surgical
      intervention is considered to be important if the symptoms show no change or
      exacerbation with conservative treatment.

PMID- 14588332
TI  - The use of presurgical psychological screening to predict the outcome of spine
      surgery.
AB  - BACKGROUND CONTEXT: Several previous studies have shown that psychosocial factors
      can influence the outcome of elective spine surgery. PURPOSE: The purpose of the
      current study was to determine how well a presurgical screening instrument could
      predict surgical outcome. STUDY DESIGN/SETTING: The study was conducted by staff
      of a psychologist's office. They performed preoperative screening for spine
      surgery candidates and collected the follow-up data. PATIENT SAMPLE: Presurgical
      screening and follow-up data collection was performed on 204 patients who
      underwent laminectomy/discectomy (n=118) or fusion (n=86) of the lumbar spine.
      OUTCOME MEASURES: The outcome measures used in the study were visual analog pain
      scales, the Oswestry Disability Questionnaire, and medication use. METHODS: A
      semi-structured interview and psychometric testing were used to identify
      specific, quantifiable psychological, and "medical" risk factors for poor
      surgical outcome. A presurgical psychological screening (PPS) scorecard was
      completed for each patient, assessing whether the patient had a high or low level
      of risk on these psychological and medical dimensions. Based on the scorecard, an
      overall surgical prognosis of "good," "fair," or "poor" was generated. RESULTS:
      Results showed spine surgery led to significant overall improvements in pain,
      functional ability, and medication use. Medical and psychological risk levels
      were significantly related to outcome, with the poorest results obtained by
      patients having both high psychological and medical risk. Further, the accuracy
      of PPS surgical prognosis in predicting overall outcome was 82%. Only 9 of 53
      patients predicted to have poor outcome achieved fair or good results from spine
      surgery. CONCLUSIONS: These findings suggest that PPS should become a more
      routine part of the evaluation of chronic pain patients in whom spine surgery is
      being considered.

PMID- 14588333
TI  - Mid-term clinical results of Graf stabilization for lumbar degenerative
      pathologies. a minimum 2-year follow-up.
AB  - BACKGROUND CONTEXT: Spinal fusion has some adverse effects, such as nonunion and
      pain at the site of grafted bone, and fusion with rigid spinal instrumentation
      especially may have the possibility of increasing mechanical stress on the
      segments adjacent to the site of fusion. The theory of the Graf system is that it
      will decrease adjacent disc deterioration because of maintenance of regional
      lordosis with flexibility and restriction of the motion of unstable segments
      without rigid spinal fusion. PURPOSE: To assess the clinical and radiologic
      results of Graf stabilization for lumbar degenerative disorders with minimal or
      mild instability. STUDY DESIGN: This is a retrospective study examining the mid
      term results of Graf stabilization. PATIENT SAMPLE: In total, 59 patients
      underwent Graf ligamentoplasty and adequate decompression from April 1993 to
      September 1997. The subjects were 30 men and 29 women, and the mean age at the
      time of surgery was 60.6 years, ranging from 23 to 82 years. The average follow
      up period was 3 years and 5 months, ranging from 2 years to 5 years and 10
      months. OUTCOME MEASURES: We evaluated the surgical results using a scoring
      system, a visual analog scale, and radiological measurements. METHODS: The
      results were assessed according to a clinical scoring system established by the
      Japanese Orthopaedic Association (JOA score) and ratings based on a visual analog
      scale. Through analysis of x-ray images, the sagittal alignment (regional
      lordosis) and the range of motion (ROM) of the stabilized segments were measured
      in all cases, and the percentage of segments slipping and posterior disc height
      were determined for 29 patients with degenerative spondylolisthesis. RESULTS:
      Clinical scores and low back pain ratings based on a visual analog scale were
      significantly improved at the time of final follow-up compared with the
      preoperative values. Regional alignment of the operative segments was maintained
      in lordosis at the time of final follow-up. Preoperative ROM was significantly
      reduced at the time of final follow-up. There were no statistical differences in
      percentage of slippage or percentage of posterior disc height between the final
      follow-up values and the preoperative values. CONCLUSIONS: Our clinical results
      indicate that the Graf system is a suitable treatment option for mild and early
      lumbar degenerative diseases with minimum flexion instability of less than 10
      degrees.

PMID- 14588334
TI  - Clinical and psychological correlates of lumbar motion abnormalities in low back
      disorders.
AB  - BACKGROUND CONTEXT: Low back pain (LBP) and low back disorders (LBDs) identify a
      complex constellation of conditions that frustrate both diagnosis and therapy.
      Dynamic quantitative assessment and questionnaire instruments directed toward
      psychosocial and situational variables provide potentially powerful tools for
      determining functional pathology and potentially outcome. PURPOSE: Our goal was
      to independently assess clinical correlates of a trunk motion measurement device,
      the lumbar motion monitor (LMM). The reliability of the LMM as a clinical test
      was assessed by comparison with an independent medical examination and
      biobehavioral questionnaires. STUDY DESIGN/SETTING: There were three study
      components. A multispecialty physician panel that administered a structured
      physical examination contributed to a clinical correlation case series study.
      Standardized outcomes and risk identification questionnaires were administered to
      the case population. Finally, the LMM was administered in a customary fashion to
      the same population. PATIENT SAMPLE: Nineteen subjects were recruited on the
      basis of criteria that included symptoms of chronic recurrent low back pain. This
      was an employed and active, although impaired, population. Eighteen of the
      subjects were currently employed with limited lost work time, but chronic and
      recurrent pain was a common feature. OUTCOME MEASURES: Questionnaire outcome
      measures were both characterologic and situation based. In addition to providing
      diagnoses, the physician panel was also asked to offer certain qualitative
      assessments, such as rehabilitative potential and functional level pertinent to
      activities of daily living. The impact of LMM measures on physician decision
      making was also assessed. Trunk angular measurements were used to assess function
      of patients with chronic low back disorders. METHODS: Kinematic performance on
      the LMM was expressed as three probability scores. These were the likelihood of
      abnormality, the "sincerity of effort" (exacerbation or aggravation of
      impairment), and the likelihood of structural anatomic disease. These variables
      were examined against established self-report measures of pain and disability.
      RESULTS: The LMM and physician panels were in agreement on the presence or
      absence of abnormality. LMM findings tended to be more consistent with clinical
      history than the clinical examination. The LMM results were also generally
      consistent with the self-reported measures of pain and disability: a high
      likelihood of structural disease was associated with depression, somatization,
      poor health perception and diminished vitality. CONCLUSIONS: The LMM appears to
      be a useful assessment tool for gauging the presence of LBP and LBD. It was
      accurate in detecting abnormality when abnormality was determined by clinical
      history and physician diagnosis. The LMM's differentiation of mechanical low back
      disease (nonanatomically specific disorders) from structurally specific low back
      disease was not consistent with a parallel clinical differentiation. Larger
      trials in a prospective format and studies on a chronically disabled population
      seem warranted. In an impaired but less disabled population, elevated pain and
      somatization did not appear to weaken the effort during testing.

PMID- 14588335
TI  - Spine policy. What's in a name?

PMID- 14588336
TI  - Arts and spine. Royal deformity: the case of Richard III.

PMID- 14588337
TI  - Spine stats. Analysis of variance.

PMID- 14588338
TI  - Spine terms. Abbreviate this!

PMID- 14588339
TI  - From the oncology department... Desmoplastic fibroma: an odd lesion in a strange
      place.

PMID- 14588342
TI  - Spine biomechanics, government regulation, and prevention of occupational low
      back pain.

PMID- 14588343
TI  - Biomechanical comparison of anterior cervical plating and combined
      anterior/lateral mass plating.
AB  - BACKGROUND CONTEXT: Previous studies showed anterior plates of older design to be
      inadequate for stabilizing the cervical spine in all loading directions. No
      studies have investigated enhancement in stability obtained by combining anterior
      and posterior plates. PURPOSE: To determine which modes of loading are stabilized
      by anterior plating after a cervical burst fracture and to determine whether
      adding posterior plating further significantly stabilizes the construct. STUDY
      DESIGN/SETTING: A repeated-measures in vitro biomechanical flexibility experiment
      was performed to investigate how surgical destabilization and subsequent addition
      of hardware components alter spinal stability. PATIENT SAMPLE: Six human
      cadaveric specimens were studied. OUTCOME MEASURES: Angular range of motion (ROM)
      and neutral zone (NZ) were quantified during flexion, extension, lateral bending,
      and axial rotation. METHODS: Nonconstraining, nondestructive torques were applied
      while recording three-dimensional motion optoelectronically. Specimens were
      tested intact, destabilized by simulated burst fracture with posterior
      distraction, plated anteriorly with a unicortical locking system, and plated with
      a combined anterior/posterior construct. RESULTS: The anterior plate
      significantly (p<.05) reduced the ROM relative to normal in all modes of loading
      and significantly reduced the NZ in flexion and extension. Addition of the
      posterior plates further significantly reduced the ROM in all modes of loading
      and reduced the NZ in lateral bending. CONCLUSIONS: Anterior plating systems are
      capable of substantially stabilizing the cervical spine in all modes of loading
      after a burst fracture. The combined approach adds significant stability over
      anterior plating alone in treating this injury but may be unnecessary clinically.
      Further study is needed to assess the added clinical benefits of the combined
      approach and associated risks.

PMID- 14588344
TI  - Development of spondylolytic olisthesis in adolescents.
AB  - BACKGROUND CONTEXT: Although it has been well documented that slippage in
      patients with spondylolysis is most prevalent during the growth period, the exact
      time when slippage initiates and halts during the growth period is still unknown.
      Moreover, the contribution of spinal deformities, such as wedging of the
      vertebral body to the slippage, remains controversial. PURPOSE: To clarify when
      slippage in pediatric spondylolysis initiates and halts. STUDY DESIGN:
      Retrospective study. PATIENT SAMPLE: We radiographically examined 46 athletes
      under 18 years of age with spondylolysis at the fifth lumbar vertebra (L5). The
      mean age at the first consultation was 13.3 years. The average follow-up period
      was 6.0 years. OUTCOME MEASURES: Longitudinal observation of slippage at L5 on
      radiogram in correlation with the maturity of the lumbar spine. METHODS: From a
      lateral radiogram of each patient, percent slippage, lumbar index (LI), and
      skeletal age of the affected vertebra were measured. Changes in the percent
      slippage over time were investigated, and the correlation between the percent
      slippage and LI was analyzed. RESULTS: From the cartilaginous stage to the
      apophyseal stage, the slippage increased in 80.0% of the patients (16 of 20).
      From the cartilaginous stage to the epiphyseal stage, slippage increased in 11.1%
      of the patients (3 of 27). None of the patients (0 of 22) showed an increase
      after the epiphyseal stage. In 20 patients in whom slippage increased during the
      follow-up period, the percent slippage at the final consultation and the LI at
      the first consultation showed no significant correlation; however, the percent
      slippage and the LI at the final consultation were significantly (p<.01)
      correlated. CONCLUSION: In conclusion, slippage was more prevalent in individuals
      of a younger skeletal age whose lumbar spine was immature, and it halted during
      the epiphyseal stage when the growth period was over and the vertebra matured.
      Furthermore, the results suggest that wedge deformity of an affected vertebra
      might be the result rather than the cause of slippage.

PMID- 14588345
TI  - SF-36 health status of workers compensation cases with spinal disorders.
AB  - BACKGROUND CONTEXT: Poorer outcomes of treatment are reported in patients with
      spinal disorders who receive workers compensation. The reason for their
      suboptimal outcomes is unclear. No study has examined the relationship between
      workers compensation and the Short Form Health Survey (SF-36) health status of
      patients with spinal disorders. PURPOSE: To compare the self-perceived health
      status of spinal disorder patients receiving workers compensation with those not
      receiving workers compensation. STUDY DESIGN/SETTING: A cross-sectional study on
      18,389 patients who were evaluated in the 28 centers comprising the National
      Spine Network. PATIENT SAMPLE: The study data were derived from patients when
      first evaluated for back or neck pain between January 1998 and April 2000.
      OUTCOME MEASURES: The outcome measures used were the eight individual and two
      component scores of the SF-36. METHODS: All first-visit patients enrolled in the
      National Spine Network from January 1998 to April 2000 were reviewed. Eight
      individual scores and two component scores of the SF-36 were compared. RESULTS:
      Of the 18,389 patients, 1,535 (8%) were receiving workers compensation. Bivariate
      analyses showed all eight individual scores, and two summary scores of the SF-36
      were significantly lower (p<.0001) in patients receiving workers compensation.
      After controlling for confounding covariates, workers compensation status was a
      significant predictor of lower SF-36 scores for General Health (p<.0001),
      Physical Functioning (p<.0001), Role Physical (p<.01), Social Functioning
      (p<.05), and Mental Health (p<.05). CONCLUSIONS: Workers compensation status is
      associated with poorer physical and mental health of patients with spinal
      disorders. Because the workers compensation group is younger, has a shorter
      duration of symptoms, and fewer comorbid medical problems, the lower SF-36 scores
      most likely reflect psychological factors and not ill health per se. The lower SF
      36 scores may also reflect premorbid personality differences in the workers
      compensation patients, compared with those not receiving workers compensation. SF
      36 is a validated tool that can be used to objectively identify the patient at
      risk for delayed recovery. Future treatment protocols should pay special
      attention to improve the health-related quality of life, especially general
      health and physical functioning of spinal patients receiving workers
      compensation.

PMID- 14588347
TI  - Endoscopic instrumentation, correction, and fusion of idiopathic scoliosis.
AB  - BACKGROUND CONTEXT: Endoscopic techniques have been used since 1993 to treat
      thoracic disk disease. Thorascopic techniques evolved into means of treating not
      only disk disease but also correcting thoracic spinal deformity with
      instrumentation and fusion. PURPOSE: To evaluate the efficacy of endoscopic
      instrumentation, correction, and fusion of thoracic idiopathic scoliosis. STUDY
      DESIGN: A retrospective review of 50 patients who have undergone endoscopic
      instrumentation, correction, and fusion for scoliosis. PATIENT SAMPLE: Fifty
      consecutive patients undergoing treatment for primary thoracic idiopathic
      scoliosis. OUTCOME MEASURES: Evaluation of operative time, curve correction, and
      fusion rates were evaluated. METHODS: Fifty patients with the diagnosis of
      primary thoracic scoliosis underwent thoracoscopic techniques of instrumentation,
      correction, and fusion. On follow-up, the patients were evaluated for spinal
      alignment restoration, axial derotation, postoperative pain, rehabilitative time,
      and complications. RESULTS: The initial curve correction averaged 50%, improving
      to over 68% in the last 10 cases. Hypokyphosis correction averaged 21 degrees.
      Additionally, there has been a decrease in rehabilitation time, less time off
      work or school, and decreased blood loss and postoperative pain. There were 14
      complications and no deaths recorded. The factors involved in a successful fusion
      include total diskectomy, complete cartilaginous end plate removal, and
      autogenous bone graft. CONCLUSIONS: The initial results of the thoracoscopic
      assisted techniques for primary thoracic scoliosis are promising. As with most
      evolving techniques, surgical times are decreasing and rates of correction are
      improving.

PMID- 14588346
TI  - Recurrent disabling work-related spinal disorders after prior injury claims in a
      chronic low back pain population.
AB  - BACKGROUND CONTEXT: Multiple compensation injury claims are an understudied
      phenomenon in the chronic back pain and occupational injury literature.
      Assumptions about poor treatment outcomes for patients presenting with prior
      injury can lead to denial of treatment, even though these assumptions have not
      been empirically addressed. Functional restoration has been demonstrated to be an
      effective rehabilitation treatment for disabling, work-related chronic back pain,
      although its' relative utility with recurrent injury (RI) patients has not been
      previously evaluated. PURPOSE: To assess demographic, psychosocial and work
      history/adjustment differences between the two groups, and to investigate whether
      patients with recurrent work-related spinal injury claims benefit from functional
      restoration treatment at a level equivalent to patients with nonrecurrent
      injuries. STUDY DESIGN/SETTING: A prospective cohort design assessing
      characteristics and outcomes of patients with recurrent work-related spinal
      disorders, compared with a group of patients without prior work-related spine
      injury claims, all treated with the same interdisciplinary rehabilitation
      protocol. PATIENT SAMPLE: A cohort of consecutively treated functional
      restoration rehabilitation patients (n=395) divided into two groups based on a
      history of prior work-related injury. The RI (n=172) group had at least one prior
      work-related injury claim (with or without lost time), whereas the nonrecurrent
      injury (NRI; n=223) group did not. OUTCOME MEASURES: The RI and NRI groups were
      assessed for prospectively collected demographic, psychosocial and work
      history/adjustment data. A structured clinical interview addressing socioeconomic
      outcomes and assessing work return, health utilization, recurrent injury and case
      closure was administered 1 year after discharge from the treatment program.
      METHODS: Consecutive patients from a regional referral center for tertiary
      rehabilitation treatment of chronic work-related musculoskeletal injuries were
      evaluated with a comprehensive biopsychosocial assessment protocol at
      pretreatment and posttreatment. Moreover, at 1 year after completing the program,
      a structural telephone interview was conducted that assessed health and
      socioeconomic outcomes. RESULTS: For the 1-year socioeconomic outcomes (such as
      posttreatment injury), the RI patients responded to rehabilitation at a level
      equivalent to the NRI patients. Demographic analyses revealed that RI patients,
      relative to NRI patients, were older, more represented by the dominant culture,
      had more education, had a shorter length of disability, had less severe types of
      injuries, had a greater rate of non-work-related health conditions, received
      higher disability payments, and had slightly greater job demand. The RI group
      also had a greater rate of pre-injury Axis I psychiatric disorders, particularly
      substance abuse/dependence disorders, than the NRI group. In addition, the RI
      group had greater job stability than the NRI group. CONCLUSIONS: The results of
      this study indicate that, although patients with recurrent injuries evidence
      differences in demographic, psychosocial and work history/adjustment differences
      when compared with patients with nonrecurrent injuries, their 1-year outcomes
      after tertiary, medically directed rehabilitation are identical. Both groups
      demonstrate very low rates of further work-related injuries through the first
      posttreatment year. Patients with recurrent injuries appear to develop skills in
      dealing with the workers' compensation system with a familiarity not seen in NRI
      patients. Of course, these results will need to be replicated in other settings
      to determine whether they can be generalized to the entire workers' compensation
      population.

PMID- 14588348
TI  - Psychological and functional profiles in select subjects with low back pain.
AB  - BACKGROUND CONTEXT: Some researchers have found a correlation of poor treatment
      outcomes in patients with low back pain and abnormal psychological profiles,
      whereas others have failed to confirm this correlation. A critical feature of
      this debate has been whether abnormal psychological profiles seen in patients
      with back pain are the result of the ongoing back pain or whether pre-existing
      psychological features predispose to a poor clinical outcome. PURPOSE: To
      determine the relationship of psychometric testing scores to the presence and
      duration of back pain of differing causes. STUDY DESIGN/SETTING: This was a
      prospective observational study of the psychological profiles of groups of
      patients with low back pain and controls. PATIENT SAMPLE: Subjects having a
      variety of painful back conditions (n=310) were compared with a control group of
      subjects without low back complaints who had undergone cervical spine surgery
      (n=73). OUTCOMES MEASURES: Psychometric testing (Modified Zung and Modified
      Somatic Pain Questionnaire) was performed along with pain scores (visual analog
      scale [VAS]), a standardized Low Back Pain Questionnaire, and the Oswestry Low
      Back Pain Disability Questionnaire in the evaluation of back pain and control
      subjects. METHODS: The subjects with painful back conditions included patients
      with presumed discogenic pain undergoing discography (n=95); patients with
      symptomatic isthmic spondylolisthesis coming to fusion (n=61); patients with
      chronic vertebral osteomyelitis before diagnosis and treatment (n=39). There was
      also a nonpatient group of soldiers with chronic low back pain not seeking
      medical care (n=115). The control subjects without low back pain consisted of a
      group who had undergone cervical spine surgery (n=73). Psychometric testing was
      performed and compared in the evaluation of subjects having these different
      painful back conditions. Analysis was done comparing pain scores, function
      scores, and psychological testing scores between the symptomatic and asymptomatic
      groups. RESULTS: The VAS maximum in last week score for the entire group was 7.1,
      and scores were not significantly different in all low back pain groups. The
      Oswestry scores were poorest in the discography group compared to
      spondylolisthesis and osteomyelitis. Functional scores were similar in the
      soldiers with low back pain and controls without low back pain. Both Depression
      and Somatic Pain scores were most abnormal in the discogenic low back pain group.
      Only 21% of this group had normal scores, compared with 71% of the
      spondylolisthesis group, 79% of osteomyelitis group, and 88% of the group with
      chronic low back pain not seeking treatment (p<.001 in all groups). The
      asymptomatic control group had 85% normal scores. CONCLUSIONS: Despite similar
      pain levels and pain duration, patients with the discographic diagnosis of
      discogenic back pain have poorer functional scores and very abnormal
      psychological scores compared with other subjects with chronic low back pain
      resulting from spondylolisthesis requiring surgery or chronic pyogenic
      osteomyelitis. Chronic moderately severe mechanical low back pain in healthy
      subjects was not associated with abnormal psychological scores or functional
      disability.

PMID- 14588349
TI  - Biochemistry of intervertebral disc degeneration and the potential for gene
      therapy applications.
AB  - BACKGROUND CONTEXT: Low back pain continues to be a major cause of morbidity in
      the United States and the world. Although the exact cause has yet to be defined,
      the intervertebral disk and its age-related changes have been most frequently
      implicated. PURPOSE: This article represents a brief summary of intervertebral
      disk structure and function, both in the "normal" and degenerative states. STUDY
      DESIGN/SETTING: Review article. A Medline search from 1966 to present was
      performed to identify pertinent articles related to the topic of the
      intervertebral disc and degeneration. METHODS: This review article describes the
      pertinent anatomy, as well as the biochemical and biomechanical changes that
      occur in the intervertebral disc over time. It presents many of the current
      theories implicated as causing these changes. RESULTS: Recent studies have shown
      that gene therapy (the transfer of therapeutic gene[s] into a cell), may have
      promise as a method of slowing down, or preventing some of the changes seen in
      the intervertebral disc. CONCLUSION: Intervertebral disc degeneration is a
      complex phenomenon, likely the result of a combination of biochemical and
      biomechanical factors that are known to occur in the disk. Ongoing research
      efforts in the area of gene therapy show promise as a way to prevent, or even
      reverse, some of these changes.

PMID- 14588350
TI  - Functional outcomes of instrumented posterior lumbar interbody fusion in active
      duty US servicemen: a comparison with nonoperative management.
AB  - BACKGROUND CONTEXT: The existing literature lacks a functional outcome study
      addressing instrumented posterior lumbar fusion surgery in physically active
      patients. Furthermore, results of operative versus nonoperative treatment in
      these patients are not clear. PURPOSE: To evaluate patient-assessed function,
      pain, and satisfaction and military job performance between servicemen treated
      operatively and nonoperatively. STUDY DESIGN/SETTING: This is a nonrandomized
      analysis of consecutive active-duty military servicemen treated either
      operatively or nonoperatively for chronic back pain and single-level lumbar disc
      degeneration with emphasis on functional outcomes. PATIENT SAMPLE: Active-duty US
      servicemen with chronic low back pain. OUTCOME MEASURES/METHODS: Twenty-nine
      consecutive active-duty US servicemen were treated for chronic back pain and
      single-level lumbar disc degeneration by the same surgeon at a military spine
      facility. Fifteen were treated with instrumented posterior lumbar interbody
      fusion (PLIF), and 14 refused surgery and chose to be treated nonoperatively with
      spinal extensor muscle-strengthening exercise, medications, and restricted duty.
      The average follow-up time was 14 months (range, 6 to 24 months). All servicemen
      completed a functional outcome questionnaire American Academy of Orthopedic
      Surgeons/Scoliosis Research Society (AAOS/SRS) with emphasis on pre- and
      posttreatment function, pain, and satisfaction. The two groups were also compared
      using military job performance parameters. RESULTS: Four of 14 (28%) of the
      servicemen treated nonoperatively ultimately received a disability discharge from
      the military for back pain, another 5 of 14 (36%) remained on permanent duty
      restriction profiles, and only 5 of 14 (36%) returned to full, unrestricted
      military duty. In the PLIF group, 12 of 15 soldiers (80%) were able to return to
      full duty, only 3 of 15 (20%) remained on permanent restrictive duty-limitation
      profiles, and 0 of 15 (0%) received a disability discharge from the military for
      back pain. Twelve of 15 (80%) of the PLIF group and 8 of 14 (57%) of the group
      treated nonoperatively were physically able to complete the posttreatment
      physical fitness test. No difference was observed between premorbid and
      posttreatment physical training (PT) test scores in either group. However, scores
      for patient-assessed posttreatment pain, function, and satisfaction were
      significantly higher in the PLIF group. Soldiers who were able to return to full
      military duty did so at an average of 2 months for the group treated
      nonoperatively (n = 5) and 4 months for the PLIF group (n = 12). Complications in
      the PLIF group included dural tear (n = 2), unilateral transient lower extremity
      paresthesia (n = 1), and wound seroma requiring reoperation (n = 1). CONCLUSIONS:
      In this nonrandomized study of 29 active-duty US servicemen with chronic low back
      pain and single-level lumbar disc degeneration, instrumented PLIF surgery was
      associated with a high rate of return to full military duty. Servicemen treated
      with this technique were less likely to receive a back pain disability discharge
      or a permanent physical limitation profile when compared with servicemen who
      chose to be treated nonoperatively. Outcomes with respect to postreatment pain,
      function, and satisfaction were higher in patients treated with instrumented PLIF
      and were excellent in servicemen who were able to return to full duty regardless
      of treatment.

PMID- 14588352
TI  - From the clinic...Diastematomyelia, when examination of the skin predicts spinal
      deformity.

PMID- 14588351
TI  - From postsurgical imaging... Marked superior and inferior migration of a dynamic
      plate after multilevel anterior corpectomy and fusion with posterior wiring.

PMID- 14588353
TI  - From the clinic...Rastersterography, by which trunk symmetry can be assessed to
      judge results of scoliosis treatment.

PMID- 14588356
TI  - Matching patient and physician expectations in spine surgery leads to improved
      outcomes.

PMID- 14588357
TI  - A column dedicated to unbiased product information would help the surgeon and the
      patient.

PMID- 14588359
TI  - The North American Spine Society focuses on multidisciplinary spine care.

PMID- 14588360
TI  - North American Spine Society 2000 presidential address.

PMID- 14588361
TI  - Changes in posterior disc bulging and intervertebral foraminal size associated
      with flexion-extension movement: a comparison between L4-5 and L5-S1 levels in
      normal subjects.
AB  - BACKGROUND CONTEXT: No previous study has used magnetic resonance imaging (MRI)
      to evaluate changes of posterior disc bulging and intervertebral foraminal size
      in the normal spine with flexion-extension movement, comparing L4-5 versus L5-S1
      intervertebral levels. PURPOSE: To determine changes in posterior disc bulging
      and intervertebral foraminal size with flexion-extension movement, comparing L4-5
      versus L5-S1 intervertebral levels. STUDY DESIGN: An in vivo study of magnetic
      resonance kinematics with spine flexion extension. METHODS: Spines of three
      volunteers with no history of low back pain were scanned in neutral, flexion, and
      extension positions in a vertically open MRI system. MRI was repeated after 6
      hours of normal activity and an additional 4 hours of heavy activity with a
      weighted vest. Posterior bulging of the intervertebral disc and the size of
      intervertebral foramen were measured at the L4-5 and L5-S1 levels. RESULTS: With
      spine flexion, posterior bulging of the discs increased at L4-5 in eight of nine
      measurements (three different spine-loading states for each of three subjects)
      and L5-S1 discs in six of nine measurements. In most cases, posterior bulging
      decreased with extension. No significant difference was noted in the degree of
      disc bulge between levels. Foraminal size at L4-5 increased with flexion and
      decreased with extension, and the extent of these changes was greater at the L4-5
      level than at L5-S1. CONCLUSIONS: This pilot study demonstrates two distinct
      behavior characteristics of the normal spine with flexion-extension movement.

PMID- 14588363
TI  - A new system of classification for spinal injuries.
AB  - BACKGROUND CONTEXT: A comprehensive classification for spinal trauma has proved
      difficult to achieve as attested to by the number of systems in use today. In
      addition, few systems can be applied to all levels of the spine, and the first
      two cervical vertebrae are usually treated as altogether separate from the
      remainder of the spine. Consequently, outcome data and comparison of published
      data are difficult, at best. PURPOSE: The purpose of this presentation is to
      introduce a new system for classification of spine trauma applicable to all
      levels of the spine. STUDY DESIGN/SETTING: A different way of viewing the
      vertebrae is proposed. It allows the inclusion of all levels of the spinal column
      in a unified classification system based on the morphology of the injury. Each
      vertebra is viewed as a bony ring, and the rings are linked, above and below, by
      three osseoligamentous structures. These are the end plate-disc-end plate
      anteriorly and the facet joints posteriorly. Equivalent structures for the links
      are defined for the atlas and axis. PATIENT SAMPLE: The x-rays and computed
      tomographic or magnetic resonance imaging of patients with spine trauma were used
      to apply this classification to acute injuries. The sample used was all patients
      with spine trauma admitted, during a 1-year period, to a level 1 trauma center.
      Not all the patients were treated by the author, and no attempt was made to
      determine indications for treatment or treatment outcomes on the basis of this
      new classification system. METHODS: A new classification retrospectively applied
      to a defined patient population, which appeared to be representative of known
      trauma patterns. RESULTS: All patients with spinal trauma in this patient
      population were classifiable by this new system. All fracture types proposed in
      this system were represented in the patient sample. CONCLUSION: This new
      classification system appears to warrant further study.

PMID- 14588365
TI  - Short-term complications and long-term results of expansive open-door
      laminoplasty for cervical stenotic myelopathy.
AB  - BACKGROUND CONTEXT: Laminoplasty has been reported to achieve good operative
      results for treatment of cervical stenotic myelopathy. However, long-term results
      and prognostic factors have not been well documented. Among postoperative
      complications, weakness of the shoulder girdle muscles has been reported as a
      particular complication of laminoplasty, but the cause is still poorly
      understood. PURPOSE: Our aim was to clarify the short-term complications and long
      term operative results after unilateral open-door laminoplasty and to identify
      the predictors for operative outcome. STUDY DESIGN: We retrospectively reviewed
      short-term complications and long-term operative results associated with cervical
      stenotic myelopathy treated by unilateral open-door laminoplasty. PATIENT SAMPLE:
      There were 162 men and 42 women with an average age of 57 years who were treated
      by unilateral open-door laminoplasty in the two institutions. Pathogenesis of
      myelopathy was cervical spondylosis in 88 patients, cervical disk herniation with
      a narrow spinal canal in 10, and ossification of the posterior longitudinal
      ligament in 106. OUTCOME MEASURES: Postoperative complications and their outcomes
      were examined clinically in 204 patients, and causes of motor paresis were sought
      with postoperative computed tomography after myelography. Postoperative
      improvement of clinical symptoms was assessed by recovery rate calculated with
      the scores of the Japanese Orthopaedic Scoring System in 80 patients. METHODS:
      The occurrence rate of short-term postoperative complications, causes of motor
      paresis, and their outcomes were reviewed in 204 patients. Clinical condition was
      assessed with the Japanese Orthopaedic Scoring System, recovery rate was
      calculated with the score, and prognostic factors for outcome were studied in 80
      patients who were followed up for 5 years or longer (average, 8 years; range, 5
      17 years). RESULTS: Occurrence rate of complications, such as muscle weakness,
      deep infection, closure of opened laminae, and others, was 10.8%. Muscle weakness
      was observed in 7.8% of the patients. However, this rate decreased in recent
      years. The cause of motor paresis is not known with certainty, but it may be
      secondary to operative trauma, posterior shift of the spinal cord, or to
      displacement of the lamina in the hinge side. Recovery rate of clinical symptoms
      was 62.1% at the final follow-up. Rates were 63.6% for cervical spondylosis,
      87.1% for cervical disk herniation, and 61.3% for ossification of the posterior
      longitudinal ligament. There was no significant difference between pathologies.
      Patient age younger than 60 years at the time of operation and less than 1 year's
      duration of symptoms before surgery were significantly associated with recovery
      rate of clinical symptoms. Recovery rate was not correlated with either
      preoperative function judged by the Japanese Orthopaedic Association score or
      spinal sagittal diameter. CONCLUSIONS: The main cause of postoperative motor
      paresis of upper extremities is thought to be operative trauma, resulting from
      such procedures as air-drill and Kerrison rongeur handling. Short-term
      complications may decrease with the use of nontraumatic procedures. Better
      operative outcomes may be achieved with careful operative procedures and early
      operative treatment in the patients with myelopathy.

PMID- 14588366
TI  - Cervicogenic headaches: a critical review.
AB  - BACKGROUND CONTEXT: The notion that headaches may originate from disorders of the
      cervical spine and can be relieved by treatments directed at the neck is gaining
      recognition among headache clinicians but is often neglected in the spine
      literature. PURPOSE: To review and summarize the literature on cervicogenic
      headaches in the following areas: historical perspective, diagnostic criteria,
      epidemiology, pathogenesis, differential diagnosis, and treatment. STUDY
      DESIGN/SETTING: A systematic literature review of cervicogenic headache was
      performed. METHODS: Three computerized medical databases (Medline, Cumulative
      Index to Nursing and Allied Health Literature [CINAHL], Mantis) were searched for
      the terms "cervicogenic" and "headache." After cross-referencing, we retrieved
      164 unique citations; 48 citations were added from other sources, for a total of
      212 citations, although all were not used. RESULTS: Hilton described the concept
      of headaches originating from the cervical spine in 1860. In 1983 Sjaastad
      introduced the term "cervicogenic headache" (CGH). Diagnostic criteria have been
      established by several expert groups, with agreement that these headaches start
      in the neck or occipital region and are associated with tenderness of cervical
      paraspinal tissues. Prevalence estimates range from 0.4% to 2.5% of the general
      population to 15% to 20% of patients with chronic headaches. CGH affects patients
      with a mean age of 42.9 years, has a 4:1 female disposition, and tends to be
      chronic. Almost any pathology affecting the cervical spine has been implicated in
      the genesis of CGH as a result of convergence of sensory input from the cervical
      structures within the spinal nucleus of the trigeminal nerve. The main
      differential diagnoses are tension type headache and migraine headache, with
      considerable overlap in symptoms and findings between these conditions. No
      specific pathology has been noted on imaging or diagnostic studies which
      correlates with CGH. CGH seems unresponsive to common headache medication. Small,
      noncontrolled case series have reported moderate success with surgery and
      injections. A few randomized controlled trials and a number of case series
      support the use of cervical manipulation, transcutaneous electrical nerve
      stimulation, and botulinum toxin injection. CONCLUSIONS: There remains
      considerable controversy and confusion on all matters pertaining to the topic of
      CGH. However, the amount of interest in the topic is growing, and it is
      anticipated that further research will help to clarify the theory, diagnosis, and
      treatment options for patients with CGH. Until then, it is essential that
      clinicians maintain an open, cautious, and critical approach to the literature on
      cervicogenic headaches.

PMID- 14588368
TI  - The relationship between disc degeneration and flexibility of the lumbar spine.
AB  - BACKGROUND CONTEXT: A relationship between degenerative changes of the
      intervertebral disc and biomechanical functions of the lumbar spine has been
      suggested. However, the exact relationship between the grade of disc degeneration
      and the flexibility of the motion segment is not known. PURPOSE: To investigate
      the relationship between degenerative grades of the intervertebral disc and three
      dimensional (3-D) biomechanical characteristics of the motion segment under
      multidirectional loading conditions. STUDY DESIGN/SETTING: A biomechanical and
      imaging study of human cadaveric spinal motion segments. METHODS: One hundred
      fourteen lumbar motion segments from T12-L1 to L5-S1 taken from 47 fresh cadaver
      spines (average age at death, 68 years; range, 39 to 87 years) were used in this
      study. The severity of degeneration (grades I to V according to Thomson's system)
      was determined using magnetic resonance (MR) images and cryomicrotome sections.
      Pure unconstrained moments with dead weights were applied to the motion segments
      in six load steps. The directions of loading included flexion, extension, right
      and left axial rotation, and right and left lateral bending. RESULTS: When the MR
      images were graded, 2 segments had grade I disc degeneration; 45, grade II; 20,
      grade III; 26, grade IV; and 21, grade V. When the cryomicrotome sections were
      graded, 14 segments had grade I disc degeneration; 31, grade II; 22, grade III;
      26, grade IV; and 21, grade V. Segments from the upper lumbar levels (T12-L1 to
      L3-4) tended to have greater rotational movement in flexion, extension, and axial
      rotation with disc degeneration up to grade IV, whereas the motion decreased when
      the disc degenerated to grade V. In the lower lumbar spine at L4-5 and L5-S1,
      motion in axial rotation and lateral bending was increased in grade III.
      CONCLUSIONS: These results suggest that kinematic properties of the lumbar spine
      are related to disc degeneration. Greater motion generally was found with disc
      degeneration, particularly in grades III and IV, in which radial tears of the
      annulus fibrosus are found. Disc space collapse and osteophyte formation as found
      in grade V resulted in stabilization of the motion segments.

PMID- 14588371
TI  - Vertebroplasty: techniques to avoid complications.
AB  - BACKGROUND CONTEXT: The use of vertebroplasty for treatment of spinal fractures
      and spinal hemangiomas is increasing at a rapid pace. Although this is a
      minimally invasive procedure, complications have been reported. The most
      important of these is the unintentional migration of polymethylmethacrylate
      (PMMA). PURPOSE: The authors present methods, equipment, and principles that
      minimize occurrence of PMMA migration and other complications. STUDY
      DESIGN/SETTING: Patients in a private/university neurosurgery practice were
      studied retrospectively by chart review. PATIENT SAMPLE: During a 3-year period,
      53 levels of vertebroplasty were performed on 35 patients presenting with
      indications of intractable pain resulting from vertebral body compression
      fractures. OUTCOME MEASURES: Pain assessment and outcome determination were made
      by the treating physician based on dialog with the patient, examination, and the
      patient's use of narcotics. The medical records of patients were reviewed for
      these factors as well as for signs of cerebrospinal fluid leak, PMMA migration,
      new radiculopathy, myelopathy, new fracture, pulmonary emboli, infection, or
      bleeding. METHODS: Criteria for inclusion consisted of disabling back pain
      corresponding to a recent fracture, pharmacotherapy, and medically stable for
      anesthesia. Vertebroplasty patients were followed up at 2 to 3 weeks and at 3
      months after their procedure. RESULTS: Success rate for relief of pain was 89%.
      The overall complication rate was 6% per treated vertebral level. There were no
      deaths or delayed complications. Factors that reduce complications were
      identified and include the following: accurate needle placement, adequate barium
      radio-opacification of PMMA, viscous low pressure delivery of PMMA, and PMMA
      delivery under direct fluoroscopic visualization. CONCLUSION: Although
      vertebroplasty is considered a minimally invasive procedure, it can result in
      serious complications even without technical misadventures.

PMID- 14588369
TI  - Predicting recovery using continuous low back pain outcome measures.
AB  - BACKGROUND CONTEXT: There is a lack of research evaluating multiple follow-up
      visits, specifically when using continuous outcome measures. Continuous outcome
      measures with several follow-up assessments would allow us to evaluate rate of
      recovery. PURPOSE: To predict low back pain outcomes based on the quantification
      of initial conditions. STUDY DESIGN/SETTING: This was a prospective study where
      patients were enrolled within the first month of low back pain symptoms and
      evaluated for 3 months. Patients were recruited from several primary care
      facilities. PATIENT SAMPLE: Thirty-two patients with local low back pain symptoms
      were recruited for the study. OUTCOME MEASURES: There were four major outcome
      measures, including functional performance probability, symptom intensity,
      impairment of activities of daily living, and a summary outcome measure. METHODS:
      Regression models were constructed using the initial conditions, including
      psychological, psychosocial, physical workplace, and personal factors, to predict
      the rate of recovery for each outcome measure. RESULTS: Twenty-eight patients
      completed the study. The r2 value for the rate of recovery regression models were
      0.77 symptom intensity prediction, 0.85 activities of daily living prediction,
      0.87 functional performance probability prediction, and 0.96 summary outcome
      measure prediction. Two functional performance patterns of recovery were found,
      including a steady improvement and a large jump in improvement. A discriminant
      function model identified the pattern of recovery in 91% of cases given initial
      conditions. CONCLUSIONS: Continuous outcome measures can be accurately predicted
      given the initial conditions.

PMID- 14588373
TI  - Spine codes.

PMID- 14588372
TI  - Spine policy.

PMID- 14588374
TI  - Spine stats.

PMID- 14588376
TI  - The faces of spine care: 1. From the Imaging Department.

PMID- 14588378
TI  - 3. From the Clinic.

PMID- 14588377
TI  - 2. From the Electrodiagnostics Lab.

PMID- 14588386
TI  - The hierarchy of clinical research studies.

PMID- 14588387
TI  - Chronic spinal disorders and psychopathology. research findings and theoretical
      considerations.
AB  - BACKGROUND CONTEXT: Numerous studies have documented a strong association between
      chronic spinal disorders and psychopathology. However, there have been
      methodological shortcomings associated with much of this. PURPOSE: This article
      reviews the relevant research literature, including methodological refinements
      that have resulted in improved measurement of psychopathology, in order to
      provide the most updated conclusions concerning the links between spinal
      disorders and psychopathology. STUDY DESIGN: A systematic review of all Medline
      referenced articles on this subject during the past three decades. METHODS:
      Previous research has shown that chronic spinal disorders are most often
      associated with depressive disorders, somatoform disorders, anxiety disorders,
      substance use disorders, and personality disorders. In addition to reviewing this
      research, the relationship between chronic spinal disorders and depressive
      disorders is examined in more detail. RESULTS: Although the relationship between
      spinal disorders and psychopathology is complex, a diathesis-stress model is
      emerging as the dominant overarching theoretical model. In this model, diatheses
      are conceptualized as pre-existing semidormant characteristics of the individual
      before the onset of chronic spinal disorders, which are then activated by the
      stress of this chronic condition, eventually resulting in a diagnosable
      depressive disorder. CONCLUSIONS: In the present review, a diathesis-stress model
      was applied specifically to the relationship between chronic spinal disorders and
      depressive disorders. Such a model may also be applicable to the relationship
      between chronic spinal disorders and other types of psychopathology, such as
      anxiety and substance use disorders. However, conclusive empirical support will
      require a prospective research design, given that these diatheses could be
      validly assessed only before the onset of the chronic pain condition.

PMID- 14588388
TI  - Effects of aerobic exercise on low back pain patients in treatment.
AB  - BACKGROUND CONTEXT: Aerobic exercise (AE) has been prescribed to improve fitness
      and well-being in apparently healthy individuals and cardiac, orthopedic, and
      other patient populations. AE has not previously been studied as a sole treatment
      for low back pain patients (LBPP). PURPOSE: This study evaluated the effects of
      low to moderate aerobic exercise as an adjunct treatment for LBPP, 30 to 60 years
      of age, in a neurosurgical practice during a 2.5-year follow-up to an initial 10
      week exercise program. The purpose of this study was to determine the effects of
      short- and long-term AE on LBPP. The initial 10-week phase compared AE and
      nonexercising controls on mood states and pain/symptoms. STUDY DESIGN/SETTING: A
      matched stratified design was used to input LBPP with similar previous clinical
      treatments as well as age and sex into AE or control groups. PATIENT SAMPLE:
      After screening 68 LBPP from a New England private neurosurgical practice, 40
      patients met qualification criteria, and 35 volunteered for this AE research
      study. The LBPP in this study were 30 to 60 years old and had the following
      medical diagnoses: herniated nucleus pulposus at one or more lumbar levels,
      degenerative discopathy, lumbosacral strain, and spinal canal and/or foraminal
      stenosis. OUTCOME MEASURES: The measure of mood states was the Profile of Mood
      States, and the measure of pain was the Brief Pain Inventory. The 2.5-year follow
      up phase compared AE and nonexercise patients on the following treatment
      variables: medical office visits for pain/symptoms, physical therapy referrals,
      epidural steroid injections for pain/symptoms, prescription of pain medications,
      and work status. METHODS: Thirty-five LBPP were matched stratified into an AE or
      nonexercise control group for a 10-week exercise program. After the 10-week
      exercise program, all subjects were given the opportunity to cross over to the
      opposite group. Those patients choosing to exercise were advised to follow a low
      to moderate aerobic exercise prescription (walking or cycling, 60% age-predicted
      maximal heart rate, 4 days per week for 45 minutes per day). None of the original
      AE group crossed over to the nonexercise group because of symptoms relating to
      their previous exercise participation. All participants were contacted at 6-month
      intervals, and the number of medical office visits for pain/symptoms, physical
      therapy referrals, number of epidural steroid injections, and number of
      prescriptions for pain was charted for 2.5 years. Work status was evaluated by
      comparing the change in number of patients not working, working part time,
      working full time, or number changing from full time to part time or not working
      from randomization to the end of follow-up. Patients following the exercise
      prescription at least 50% of the time were compared with those exercising less
      than 50% of the time during the 2.5-year follow-up. Significance was determined
      at the.05 level using Fisher's exact test or the Kruskal-Wallis test. RESULTS:
      The initial 10-week AE phase of the study indicated that low to moderate AE
      significantly improved mood profile (AE X=-9.58; control X=19.11; p<.01) but did
      not alter pain levels. AE patients in the 2.5-year follow-up phase received
      significantly fewer pain medication prescriptions (AE X=2.76; control X=13.35;
      p<.02) and were given fewer physical therapy referrals (AE X=0.17; control
      X=1.64; p<.002). There was no significant difference in the number of medical
      office visits for pain or epidural blocks administered to either group. Work
      status was improved only in exercising patients (AE X=+0.24; control X=-0.35;
      p<.04). CONCLUSIONS: Low to moderate aerobic exercise appears to improve mood
      states and work status and reduce the need for physical therapy referrals and
      pain medication prescriptions for LBPP in the care of a neurosurgeon.

PMID- 14588389
TI  - Evaluation and analysis of patient outcomes with an intrasegmental fixation
      system in lumbar spinal fusion.
AB  - BACKGROUND CONTEXT: A new spinal fixation system with polydirectional screws and
      modular links with interconnecting radial serrations has been developed. The
      system allows the linking of multiple points of fixation, two points at a time
      (intrasegmental fixation), thus eliminating the need for intraoperative
      contouring of rods or plates. PURPOSE: Evaluation of this new type of spine
      system was done through biomechanical studies, analysis of lumbar lordosis
      preservation postoperatively, and multicenter review of patient outcomes with a
      minimum of 1 year follow-up. STUDY DESIGN/SETTING: Biomechanical studies of the
      spine system were performed according to American Society for Testing and
      Materials (ASTM) standards. To evaluate the maintenance of lordosis, radiographs
      from the first 119 patients were reviewed by the authors. Analysis of patient
      outcomes consisted of a review of the first 259 patients who underwent spinal
      fusion surgery with the new spine system. PATIENT SAMPLE: Evaluation of patient
      outcomes consisted of 122 men and 137 women with an average age of 50+/-13 years
      (range, 22-96 years) and a mean follow-up of 20+/-6 months (range, 12-54 months).
      The patient population was at high risk for fusion failure, with 127 smokers
      (49%), 141 who had previous spine surgery (54%), 22 with osteoporosis (8%), 63
      were obese (24%), and 32 with diabetes (12%). One hundred two patients (39%) had
      a one-level fusion, 105 patients (41%) had two levels fused, and 52 patients
      (20%) had three or more levels fused. The majority of patients (66%) were covered
      under workers' compensation. OUTCOME MEASURES/METHODS: Radiographic fusion was
      deemed successful when the presence of trabecular bridging bone from transverse
      process to transverse process was observed, as well as no fixation failure nor
      radiographic evidence of screw loosening. Clinical success was rated excellent,
      good, fair, or poor depending on the patients pain level, function, and pain
      medication intake. RESULTS: Biomechanical studies of this intrasegmental fixation
      system have shown it to be strong under both static and fatigue testing, with
      exceptional strength in compression bending. In evaluating preservation of lumbar
      lordosis, no statistically significant loss of lordosis was observed. Overall,
      radiographic fusion was noted in 229 of 259 patients (88%) and did not differ
      significantly (p>.10) by the number of levels fused. Clinically, 69 patients
      (27%) had an excellent result, 111 patients (43%) had a good result, 50 patients
      (19%) had a fair result, and 29 patients (11%) had a poor result. The high rate
      of successful patient outcomes did not differ significantly (p>.10) by the number
      of levels fused, or other patient or surgical variables, except for the
      satisfaction level of workers' compensation versus nonworkers' compensation. One
      hundred of 118 patients (85%) who were working before surgery returned to work at
      an average 9+/-4 months postoperatively (range, 2-20 months). The use of direct
      current (DC) stimulation in this population was reserved for patients with one or
      more risk factors for fusion failure and was noted to be of benefit. There were
      no recorded intraoperative complications, but postoperatively 5 device and 19 non
      device-related complications (9%) were noted, which is comparable to other lumbar
      fusion series. CONCLUSIONS: The results of these analyses show consistent patient
      outcomes regardless of the number of levels fused with an intrasegmental system.
      This may be attributable to the increased biomechanical strength of the system at
      each segment, coupled with the ability of intrasegmental fixation to maintain
      sagittal plane balance through preservation of the patient's lordotic curve.

PMID- 14588390
TI  - Lumbosacral fixation using expandable pedicle screws. an alternative in
      reoperation and osteoporosis.
AB  - BACKGROUND CONTEXT: Pedicle screw fixation in osteoporotic bone and in revision
      of previous pedicle screw fixation cases presents a significant challenge to
      spine surgeons. Biomechanical tests have shown that a pedicle screw that expands
      within the vertebrae body can substantially improve fixation in the presence of
      compromised bone. PURPOSE: To review the clinical and radiographic results with
      the use of expandable pedicle screws. STUDY DESIGN: One hundred forty-five
      patients received one or more expandable pedicle screws from the Omega21 spinal
      fixation system (EBI, L.P., Parsippany, NJ) to obtain thorocolumbar or
      lumbosacral stabilization. PATIENT SAMPLE: The indications for use of the
      expandable screws were osteoporosis (21 cases), reoperation of previous pedicle
      instrumentation (27 cases), intraoperative screw relocation (17 cases), construct
      reinforcement (23 cases), and sacral anchoring to avoid the necessity of anterior
      penetration of the sacral cortex (57 cases). OUTCOME MEASURES: The presence of
      radiographic fusion and complications arising from the instrumentation were
      reviewed at a mean follow-up period of 35 months (range, 24-72 months). METHODS:
      A retrospective clinical and radiographic review was performed. Fusion was
      evaluated based on anterior-posterior and lateral radiographs as well as dynamic
      radiographs in flexion and extension. RESULTS: Radiographic evidence of fusion
      was obtained in 125 of the 145 cases (86%). Eighty-six percent of patients with
      osteoporosis and 89% of reoperations fused. There were no instances of screw
      loosening or pullout of the expandable screws. Screw breakage occurred in four
      patients (2.8%), including three patients where fusion was not obtained. In six
      patients the expandable screws were removed without difficulty after fusion
      because of local discomfort. CONCLUSION: The results of this study have shown
      that expandable pedicle screws can be efficacious in cases in which pedicle screw
      fixation is difficult and adds a valuable tool to the growing armamentarium of
      spinal instrumentation.

PMID- 14588391
TI  - The axial cage. a pilot study for interbody fusion in higher-grade
      spondylolisthesis.
AB  - BACKGROUND CONTEXT: The surgical treatment of high-grade spondylolisthesis is
      challenging. Posterolateral fusion alone has a high rate of pseudarthrosis.
      Surgical stabilization of higher-grade lumbar spondylolisthesis with a fibula
      strut graft is an effective technique but is associated with harvest site
      morbidity and graft fractures. PURPOSE: We hypothesized that a lumbar interbody
      fusion with a long, threaded titanium cage, packed with cancellous bone, inserted
      across the center of the spondylolisthesis, would provide the rigid
      immobilization necessary for successful arthrodesis. This would, therefore,
      eliminate the need for fibula harvest and possibly reduce the need for posterior
      instrumentation. STUDY DESIGN/SETTING: Prospective, study cohort of 11
      consecutive patients with a minimum follow-up of 1 year. PATIENT SAMPLE: Patients
      with higher-grade spondylolisthesis (grade II-IV) were considered eligible.
      OUTCOME MEASURES: Pain was measured with a 10-point Numerical Rating Score (NRS).
      The Oswestry Disability Index (OSI) was used to assess patient function. Patients
      also responded to a satisfaction scale to evaluate satisfaction with their
      outcome. Radiographs were reviewed 1, 3, 6, 12, and, when available, 24 months
      after surgery. METHODS: We reviewed our clinical results and technical outcomes
      in 11 consecutive patients who underwent this unique form of anterior lumbar
      interbody fusion with a custom axial cage. RESULTS: There were no surgical or
      postoperative complications. Serial x-rays revealed no implant subsidence or
      loosening. There have been no implant fractures or reoperation. Clinical results
      have been excellent with significant pain reduction and improved function. At 1
      year after surgery the mean NRS was 3.5 (range, 0-7), a significant average
      reduction of 5.0 points. (p<.001) All patients have been satisfied with their
      results. CONCLUSIONS: The axial cage technique appears to be a significant
      improvement over the fibular strut graft for the treatment of higher-grade
      spondylolisthesis. It provides significant reduction in pain, significant
      improvement in function, high patient satisfaction, and avoids the morbidity and
      fracture risks associated with fibular strut grafting.

PMID- 14588392
TI  - Biomechanics of spinal manipulative therapy.
AB  - BACKGROUND CONTEXT: Modern scientific investigations into spinal manipulative
      therapy (SMT) began in 1975. Conditions often treated include acute and chronic
      low back pain, radicular pain, neck pain, and some forms of headache. The field
      of spinal manipulation has often been treated by the literature, incorrectly, as
      being homogeneous. Much of the confusion regarding this form of treatment can be
      traced to the ambiguity surrounding the procedures themselves. This report
      summarizes the clinical biomechanics of SMT and evidence for its associated
      manipulable lesion is reviewed. Finally, a classification system based on
      biomechanics is proposed that may facilitate more detailed research in the
      future. PURPOSE: A categorization system for SMT was sought that would be more
      objective than is clinically available. Such a system may serve as a means to
      strengthen future studies, determine operating principles, applicability,
      treatment effectiveness, and nature of the manipulable lesion. STUDY DESIGN:
      Literature synthesis. METHODS: A search of the indexed biomechanical and medical
      literature as well as a hand search of published works was conducted. The
      criteria for article selection consisted of studies that included measurements of
      mechanical characteristics of treatment techniques used under the general
      headings of SMT or manual therapy. A second set of studies was identified that
      explored the biomechanics of buckling behavior of vertebral segments as a model
      of the manipulable lesion. Quantitative characteristics of SMT were extracted and
      grouped to form a basis for classification. RESULTS: A total of 31 articles were
      identified that contained quantitative data on the biomechanical properties of
      SMT methods. An additional seven studies were found that quantified spinal
      buckling behavior. Common features of SMT procedures lead to a matrix that
      biomechanically characterizes the types of procedures in use. Buckling behavior
      was compared qualitatively with clinical observations to form a plausible and
      evidence-based hypothesis of the manipulable lesion. CONCLUSIONS: There currently
      are a number of named systems of manual procedures. No current triage system is
      available that predicts which patient has the greater likelihood of benefiting
      from manual treatment or the procedure type. The biomechanical parameters of SMT
      form a systematic characterization of manual procedures. Such a system may be
      used in future studies to test hypotheses of treatment effect from quantitatively
      defined procedures.

PMID- 14588393
TI  - Instrumented posterolateral lumbar fusion using coralline hydroxyapatite with or
      without demineralized bone matrix, as an adjunct to autologous bone.
AB  - BACKGROUND CONTEXT: Autogenous posterolateral fusion with and without
      instrumentation has been reported with good results. However, difficult-to-fuse
      patients, such as smokers, elderly patients with poor bone quality and/or
      quantity, or patients with prior posterior surgeries, may have somewhat lower
      fusion rates. PURPOSE: To determine the efficacy of coralline hydroxyapatite with
      or without demineralized bone matrix as a bone graft extender in a human clinical
      model with long-term follow-up. STUDY DESIGN/SETTING: A retrospective series of
      40 patients undergoing instrumented autogenous posterolateral lumbar fusion
      augmented with coralline hydroxyapatite with or without demineralized bone
      matrix. PATIENT SAMPLE: Long-term clinical and radiographic follow-up were
      examined for 40 patients who underwent an instrumented posterolateral fusion
      only. Patients undergoing anterior lumbar interbody fusion (ALIF) procedures were
      not considered part of the sample. METHODS: All patients underwent successful
      transpedicular fixation with autogenous posterolateral lumbar fusion. Fifteen cc
      of Pro Osteon 500 coralline hydroxyapatite (Interpore Cross International,
      Irvine, CA) was used at each level. An additional 10 cc of Grafton demineralized
      bone matrix gel (Osteotech, Eatontown, NJ) was used in 70% of these patients.
      RESULTS: An overall fusion rate of 92.5% was achieved. Pain and function
      improvement were good but somewhat age dependent and correlated with the number
      of comorbidities. Patients with Grafton DBM gel had a lower fusion rate of 89.3%.
      CONCLUSIONS: Based on this small retrospective review, coralline hydroxyapatite
      is an effective bone graft extender in difficult-to-fuse patients as an adjunct
      to autologous bone for posterolateral fusion of the lumbar spine when combined
      with rigid instrumentation.

PMID- 14588394
TI  - Cost-effectiveness studies of medical and chiropractic care for occupational low
      back pain. a critical review of the literature.
AB  - BACKGROUND CONTEXT: Back pain is the single most costly work-related injury.
      Chiropractors and physicians are the main primary care providers for occupational
      low back pain (OLBP), but there is no consensus regarding the relative cost
      effectiveness of these two modes of care. PURPOSE: To critically appraise and
      synthesize recent literature on the cost-effectiveness of medical and
      chiropractic care for OLBP, and to propose a cost-effectiveness methodology that
      integrates epidemiologic and economic methods for future studies. STUDY DESIGN:
      Literature review. MEDLINE was searched from 1990 through 1999. Nine articles
      that met the inclusion criteria were reviewed. The methodological quality of the
      articles was critically appraised independently by two epidemiologists using
      standardized review criteria. Two health economists reviewed the studies on cost
      effectiveness. RESULTS: The current literature suggests that chiropractors and
      physicians provide equally effective care for OLBP but that chiropractic patients
      are more satisfied with their care. Evidence on the relative costs of medical and
      chiropractic care is conflicting. Several methodological deficiencies limit the
      validity of the reviewed studies. No studies combine high-quality cost data with
      adequate sample sizes and controls for confounding factors. CONCLUSION: Existing
      studies fail to clarify whether medical or chiropractic care is more cost
      effective. We suggest that future studies must combine epidemiologic and economic
      methods to answer the question adequately.

PMID- 14588396
TI  - Arts and spine. Leonardo and the spine.

PMID- 14588398
TI  - Spine stats. The Kruskal-Wallis and Wilcoxon-Mann Whitney tests.

PMID- 14588397
TI  - Spine and the law. Pedicle screws.

PMID- 14588399
TI  - 1. From the imaging department... Extra foraminal disc herniation at a
      spondylolytic segment, by which high-quality magnetic resonance images helped
      avert surgical misadventure.

PMID- 14588400
TI  - 2. From the electrodiagnostics lab... Electromyography disease, by which thorough
      sampling avoids misinterpretation.

PMID- 14588401
TI  - 3. From the oncology department...A sacral tumor of extraordinary size, where
      bowel and bladder dysfunction were not presenting symptoms.

PMID- 14588405
TI  - "Failed conservative care": always define what treatment was received.

PMID- 14588406
TI  - "Failure of conservative care" may be a result of inadequate care rather than
      good nonoperative management.

PMID- 14588407
TI  - "Conservative" should not be equated with "nonoperative".

PMID- 14588409
TI  - Low-field-strength (open) MRI do not deliver the information needed to plan
      lumbar microdisectomy and/or microdecompression.

PMID- 14588410
TI  - To the editor:.

PMID- 14588412
TI  - MMPI-2 interpretation and closed-head trauma: cross-validation of a correction
      factor.
AB  - A substantial body of research suggests that the MMPI-2 contains a number of
      items that are sensitive to closed-head trauma (CHT) and other neurologic
      conditions. A correction procedure was recommended by Gass (1991) using an index
      consisting of 14 neurologically sensitive items that were extracted from a
      predominantly male veteran sample of CHT patients. The generalizability of these
      correction items was assessed in the present study by investigating the MMPI-2
      scoring characteristics of an outpatient referral sample of 54 CHT patients (28
      male, 26 female) who had sustained recent and mild head trauma. Their frequency
      of endorsement of MMPI-2 was contrasted with that of the MMPI-2 normative sample
      (N = 2,600). Chi-square analyses identified the 15 MMPI-2 items that best
      differentiated this CHT sample from normal subjects. The results indicate that:
      (a) unlike those in an inpatient psychiatric sample (n = 524), the MMPI-2 items
      that best distinguished the CHT Ss from normals consisted of neurologic symptom
      content; (b) of these 15 items, 10 were included in the 14-item correction (Gass,
      1991); and (c) 13 of the 14 correction items effectively discriminated the cross
      validation sample of CHT Ss from normals. These findings offer empirical support
      for the application of the MMPI-2 correction with patients who have mild and
      recent head trauma.

PMID- 14588411
TI  - The detection of simulated malingering using a computerized category
      classification test.
AB  - A category classification test was used to differentiate between normal student
      control participants, students instructed to malinger a memory deficit, and
      amnesic patients. Controls (N = 44) and amnesic patients (N = 10) were instructed
      to do their best, while simulators of malingering (N = 43) were instructed to
      fake a memory deficit for credit and possible financial compensation.
      Participants studied a list of high distortions of a prototype dot pattern and
      were then asked to choose whether or not a new set of dot patterns (random
      patterns, high distortions, low distortions, and the prototype) belonged to the
      same category of dot patterns as studied. Malingerers performed significantly
      worse than normal controls and amnesic patients. A discriminant function analysis
      showed that the classification test can be used to correctly classify
      participants as simulated malingerers, controls, or amnesic patients
      significantly higher than chance. These results indicate that a category
      classification test can be used in the detection of simulated malingering and
      that some tests of implicit memory provide a potential supplement to standard
      forced choice tests in the detection of malingering.

PMID- 14588413
TI  - The implications of limitations in hydrocarbon research for neuropsychological
      assessment.
AB  - As neuropsychologists are involved increasingly in the neuropsychological
      assessment of individuals reporting both acute and long-term exposure to
      hydrocarbons, the value of research for providing guidance also increases.
      Research findings inform neuropsychologists about likely neuropsychological
      deficits given certain intensity and duration of exposure and about
      neuropsychological tests most appropriate for detecting hydrocarbon-induced
      deficits. Although high-dose events are associated with neuropsychological
      deficits, methodological weaknesses in the existing research impede a consensus
      on the implications of low-dose exposures in humans. Three flaws inherent in
      research on low-dose hydrocarbon exposures and their implications for
      neuropsychological assessment of individuals are discussed: Selection bias in
      recruitment of research participants, biased recall of research participants, and
      between-study variation in neuropsychological tests and results. Because they
      undermine the reliability and validity of existing research, lack of awareness of
      these weaknesses may interfere with unbiased assessment of individual patients
      suspected of hydrocarbon-induced neuropsychological deficits. Examples from the
      social-cognitive psychological literature contribute to understanding how
      misleading research findings can lead experts to form expectancies that bias
      assessment of individuals.

PMID- 14588414
TI  - Neuropsychological profiles of children diagnosed as specific language impaired
      with and without hyperlexia.
AB  - This study compared the neuropsychological profiles of 46 children with Specific
      Language Impairment (SLI) and 16 children with SLI and Hyperlexia (SLI + H). The
      results indicated that the essential feature of Hyperlexia is Specific Language
      Impairment and not reading disability. Thus, Hyperlexia would be best
      conceptualized as a subgroup of Developmental Language Disorder rather than as a
      subgroup of Developmental Dyslexia. Further, the SLI + H group exhibited
      significantly better developed visual/spatial memory which, along with average
      visual perceptual skills, appears to be the major contributing factor to their
      elevated word recognition and spelling ability. Finally, it should be noted that
      both groups of children exhibited decreasing performance on tasks of immediate
      auditory/verbal memory as the language/semantic demands of the memory task
      increased. This finding appears to be the result of a limited capacity for
      immediate verbal processing and not the result of a deficit in verbal learning
      and recall.

PMID- 14588415
TI  - The effect of warning on malingering on memory and motor tasks in college
      samples.
AB  - The effect of a warning regarding detection of simulated cognitive and motor
      deficits on the Wechsler Memory Scale-Revised (WMS-R; Wechsler, 1987) and Grooved
      Pegboard (Klove, 1963; Matthews & Klove, 1964) was examined. Undergraduates (N =
      87) were randomly assigned to one of three conditions: simulators without
      warning, simulators with warning, and controls. It was predicted that warning
      participants that simulation efforts will be detected would reduce malingering
      behavior and this hypothesis was generally supported. Analyses indicated
      simulators with warning frequently approximated control group performances and
      were significantly better than simulators without warning on some measures.
      Stepwise discriminant function analysis accurately classified 57% of all
      participants. Results provide support for effectiveness of warning in reducing
      malingering behavior on selected measures and are discussed in terms of the use
      of warning as an adjunct to existing procedures, role of the neuropsychologist,
      and informed consent for assessment in personal injury litigation.

PMID- 14588416
TI  - Dementia associated with periventricular and deep white matter alterations: a
      subtype of subcortical dementia.
AB  - This research examined the neuropsychological functioning of demented patients
      with periventricular and deep white matter alterations. Thirty-three outpatients
      with NINCDS-ADRDA probable Alzheimer's disease (AD) and 27 outpatients with
      probable/ possible ischaemic vascular dementia (IVD, Chui et al., 1992)
      associated with periventricular and deep white matter alterations matched for
      age, education, level of dementia, and functional disability were studied. White
      matter alterations were measured using a 40-point scale previously described by
      Junque et al. (1990). Subjects with cortical CVAs were excluded. On executive
      control tests, IVD subjects made more preservations on tests of mental control
      and response set, and produced fewer responses on phonemic controlled oral word
      association tests (letters: F,A,S). IVD subjects also made more preservations and
      graphomotor errors on clock drawings. On the California Verbal Learning Test the
      IVD group performed better than AD subjects on the short delay free recall test
      condition, the recognition discriminability index, and made fewer intrusion
      errors on both free and cued recall conditions. We conclude that
      neuropsychological assessment can differentiate AD from IVD associated with white
      matter alterations, and that the neuropsychological profile of demented subjects
      with significant periventricular and deep white matter alterations is similar to
      other subcortical dementing illnesses.

PMID- 14588417
TI  - Patterns of performance by neuropsychiatric patients on the halstead category
      test: evidence for conceptual learning in schizophrenic patients.
AB  - We attempted to determine whether schizophrenic patients can improve their
      performance on an abstract reasoning task through experience, and to ascertain
      how the degree of learning compares with brain-damaged patients and patient
      controls. Two hundred and two schizophrenic patients, 179 brain-damaged patients
      and 229 patient controls were compared with regard to their improvement on
      Subtest 6 relative to Subtest 5 of the Halstead Category Test. Since Subtests 5
      and 6 are based on the same concept, experience with Subtest 5 should reduce
      errors on Subtest 6. Subjects were also compared on Subtest 7, which evaluates
      learning and retention of the concepts associated with subtests 1 to 6. the
      schizophrenic subjects showed improvement on subtests 6 relative to 5 that was
      equal to the controls, with both groups showing significantly greater improvement
      than the brain-damaged subjects. The schizophrenic subjects also obtained a
      better mean score on Subtest 7 than did the brain-damaged subjects, but made
      significantly more errors than controls. We conclude that schizophrenic patients
      are capable of conceptual learning, and may not have fixed, irreversible
      impairment of abstraction ability.

PMID- 14588418
TI  - Early identification of dementia: predictive validity of the clock test.
AB  - Various clock scoring procedures have been developed in recent years as dementia
      screening measures. The current longitudinal study was developed to assess the
      predictive validity of the Clock Test (Tuokko, Hadjistavropoulos, Miller, Horton,
      & Beattie, 1995). Within a sample of subjects who initially did not meet dementia
      criteria, Clock Test scores (drawing, setting, and reading) distinguished between
      those who later met criteria for dementia as compared to subjects who did not.
      When impaired performance was identified as falling below cut-off on two or more
      subtests of the Clock Test, sensitivity and specificity were found to be 91% and
      95% relative to time two diagnosis. Clock errors among the current sample were
      compared against normal control subjects from the Canadian Study of Health and
      Aging (CSHA). These comparative analyses attest to the relative normality of the
      clinic sample at the time of their initial assessment.

PMID- 14588419
TI  - Subscale validity of the Mattis Dementia Rating Scale.
AB  - The Mattis Dementia Rating Scale (DRS), a widely used dementia screening
      instrument, generates five subscale scores in the areas of Attention (ATT),
      Initiation-Perseveration (IP), Construction (CN), Conceptualization (CON), and
      Memory (MEM). The present study sought to determine the criterion validity of the
      DRS subscales in a sample of 50 patients with Alzheimer's disease (25 with mild
      and 25 with moderate dementia). Subject performance on the five DRS subscales was
      correlated with performance on five well-validated neuropsychological criterion
      measures using Pearson r and stepwise regression. On a univariate level, each DRS
      subscale correlated most strongly with its assigned neuropsychological criterion
      measure. On a multivariate level, each DRS subscale emerged as the Step 1
      predictor of its assigned criterion measure, with the exception of DRS CN, which
      was the Step 2 predictor. The results suggested that overall the DRS subscales
      are valid measures of their respective constructs and have value for both
      clinical and research purposes in mild and moderate dementia.

PMID- 14588421
TI  - Neuropsychological information in the Wechsler Adult Intelligence Scale-Revised.
AB  - The relationships among Wechsler Adult Intelligence Scale-Revised profiles (WAIS
      R), Luria-Nebraska Neuropsychological Battery (LNNB) profiles and Halstead Retian
      Neuropsychological Battery (HRNB) profiles were examined in two samples of
      patients referred for neuropsychological evaluation. Canonical correlation
      analysis suggested that the average level of WAIS-R profiles was related to the
      average level and scatter of LNNB profiles, Overall performance on the HRNB was
      less strongly related to overall performance on the WAIS-R than was the LNNB.
      Patients who were similar to a WAIS-R modal profile characterized by relative
      deficits on performance subtests were more likely to be similar to LNNB modal
      profiles characterized by relative impairments on sensorimotor subtests. Patients
      who were similar to a WAIS-R modal profile characterized by relative deficits on
      verbal subtests were more likely to be similar to LNNB modal profiles
      characterized by relative impairments on either language subtests or conceptual
      subtests. Patients classified into an HRNB profile type characterized by
      strengths on the Aphasia Screening subtest were more likely to show strengths on
      WAIS-R verbal subtests. However, less than 8 % of the total samples could be
      jointly classified into both the requisite WAIS-R profile clusters and one of the
      associated LNNB or HRNB profile clusters. WAIS-R subtest profile level may be a
      useful statistic to screen for neuropsychological deficits, but WAIS-R patterns
      are essentially useless for neuropsychological screening. Discussion focuses on
      the role of the WAIS-R in neuropsychological evaluations.

PMID- 14588422
TI  - Black-white differences in memory test performance among children and
      adolescents.
AB  - Racial differences on mental test scores are some of the most well-documented
      findings in the study of individual differences, yet only in the past 10 years
      have neuropsychologists undertaken serious examination of ethnic and related
      demographic concomitants of neuropsychological test performance. The present
      study examined performance differences for blacks and whites on 14 separate
      measures of short-term memory. Using a nationally stratified (gender, race, age,
      SES, region, and community size) population proportionate sampling plan, 168
      black and 983 white children and adolescents (ages 5 years to 19 years) were
      tested. Age corrected deviation scaled scores (mean of 10 and SD of 3) were
      calculated at 1 year intervals using the method of rolling weighted averages. In
      sharp contrast to typical findings with intellectual and most other aptitude
      measures, only one significant difference occurred across race on any of the 14
      measures of memory.

PMID- 14588423
TI  - Clinical course of neuropsychological functioning after chronic exposure to
      organic and inorganic lead.
AB  - This case series describes the clinical course (12- to 28-month follow-up) of
      neuropsychological functioning in 23 workers who had chronic occupational
      exposure to a mixture of organic and inorganic lead. Significant improvement in
      performance was seen in 123 tests and deterioration in 323 tests. However, there
      was no significant change in the majority of tests (1923). Tests that showed
      deterioration were all tests of psychomotor/motor speed. In addition, 10 of 13
      workers who completed a symptom checklist twice reported more frequent physical,
      cognitive, and affective symptoms at follow-up. This increase in symptoms was
      associated with psychomotor/motor slowing as compared to initial test
      performance. Many workers subjectively reported an increased frequency of memory
      and concentration problems at follow-up, although this change could not be
      documented objectively. Individual worker demographic and exposure
      characteristics were not predictive of changes in neuropsychological performance
      at retest. We propose a psychosocial mechanism to explain the increase in symptom
      severity and the psychomotor/motor slowing because environmental levels of lead
      declined during the inter-test interval.

PMID- 14588424
TI  - Clinical utility of a seven subtest WAIS-R short form in the neuropsychological
      assessment of traumatic brain injury.
AB  - Comparison of IQ scores from the standard Wechsler Adult Intelligence Scale
      Revised (WAIS-R) and the Ward (1990) seven-subtest short form (WAIS-R/7 SF) was
      performed on a sample of 459 patients with traumatic brain injury due to head
      trauma. The results indicate that this short form provides Verbal, Performance,
      and Full Scale IQ scores that vary little from the complete WAIS-R, at
      approximately one-half the typical administration time. The seven subtest short
      form predicted WAIS-R Full Scale IQ within 6 points in 95% of this clinical
      sample, with Verbal-Performance IQ discrepancies that were highly correlated
      (r(s) =.85, p <.0001). No differential gender effect in proration of IQs was
      found. Applications and pitfalls of abbreviated neuropsychological testing
      batteries are discussed, with utilization of the WAIS-R/7 SF offered as a means
      to reduce intelligence testing time while maintaining the ability to detect
      subtle information processing abnormalities with appropriate supplemental tasks.

PMID- 14588425
TI  - Using the neurobehavioral cognitive status examination as a screening measure for
      older adults.
AB  - We evaluated the ability of the Neurobehavioral Cognitive Status Examination
      (NCSE) to accurately distinguish between healthy older adults and geriatric
      patients suffering from dementia. Although the NCSE correctly identified all
      dementia patients, it produced an unacceptably high rate of false positives among
      the healthy elderly (70%). Despite the NCSE's lack of specificity when using the
      recommended classification criteria, significant group differences were found on
      several individual subscales and on the total number of subscales passed. These
      findings suggest the need to further evaluate the appropriateness of the
      geriatric norms for the NCSE and highlight some of the unique considerations
      involved in the assessment of older adults.

PMID- 14588426
TI  - The detection of simulated malingering using a computerized priming test.
AB  - A word completion priming test was used to differentiate between normal student
      control subjects and students instructed to malinger. Controls (n = 60) were
      instructed to do their best, while malingering subjects (n = 60) were instructed
      to fake a memory deficit for credit and possible financial compensation. Subjects
      initially rated and completed stems for words that had at least 10 possible
      completions. Thirty minutes later, subjects rated and completed stems for words
      that were either uniquely defined by the stem or could only be completed with a
      variation of the word. Simulated malingerers and controls differed significantly
      on response latencies (time to produce rated words-time to produce baseline
      words, 10 second time limit) and priming scores. Discriminant function analyses
      showed that as high as 92% of the controls could be correctly identified, and 73%
      of the malingerers could be correctly identified. These results indicate that
      priming tests can be used in the detection of malingering.

PMID- 14588427
TI  - Monitoring recovery from traumatic brain injury using automated
      neuropsychological assessment metrics (ANAM V1.0).
AB  - Twenty-two students in the Coastline Community College Traumatic Head Injury
      Program completed two sessions of neuropsychological testing spaced 2-3 months
      apart, using ANAM V1.0. Eight (GP1) were marginally injured, seven (GP2) mildly,
      and seven (GP3) moderately. Comparisons of first-session accuracy scores with
      normative data revealed that GP1 was impaired on one test, while GPs 2 and 3 were
      impaired on 3 and 4 tests, respectively. Second-session accuracy scores were
      normal for GPs 1 and 2 on all tests, and impaired on one for GP3. Comparisons of
      first-session efficiency scores with normative data indicated that GP1 was
      significantly impaired on 2 tests, while GPs 2 and 3 were impaired on all 6.
      Second-session efficiency scores were normal for GP1 on 5 tests; GPs 2 and 3 also
      improved but remained impaired on all 6 tests. Based on efficiency, 91 % of the
      individuals were correctly classified.

PMID- 14588428
TI  - A case of reversible steroid dementia.
AB  - Psychotropic effects of corticosteroids have been reported since early 1950.
      Dementia-like cognitive changes in patients undergoing treatment with high doses
      of corticosteroids were identified in 1984. The clinical presentation of these
      "steroid dementia" patients mimicked those typical of early Alzheimer's disease.
      As with psychiatric side effects of corticosteroid use, the "dementia" is
      reversible. The case presented describes a patient who developed dementia-like
      cognitive changes and an abnormal EEG as a result of steroid treatment. The case
      is of interest not only as an example of steroid dementia, but also because it is
      the first with documented electroencephalographic sequelae and premorbid EEG, CT
      scan and neuropsychological testing.

PMID- 14588429
TI  - Disturbance of social cognition after traumatic orbitofrontal brain injury.
AB  - A patient with traumatic orbitomedial frontal lobe damage demonstrated good
      neurocognitive recovery but a lasting, profound disturbance of emotional
      regulation and social cognition. Initial neuropsychological findings included a
      complete anosmia, mildly reduced fluency and disturbed motor regulation. The
      impairments of fluency and motor regulation resolved, and formal measures of
      "frontal lobe" functioning were generally intact. However, she remained impaired
      on tasks requiring the interpretation of social situations, which mirrored her
      impairment in real life functioning. This disturbance in social cognition
      appeared related to difficulty appreciating and integrating the relatively subtle
      social and emotional cues required for the appropriate interpretation of events.
      The patient's presentation represents an intermediate position between patients
      with profound neurobehavioral deficits and patients with impaired real-life
      social cognition despite intact neuropsychological performance following
      orbitofrontal damage. Variations in the orbitofrontal behavioral syndrome may be
      related to extent of lesion, time post injury and the course of recovery in
      different patients.

PMID- 14588430
TI  - Efficacy of neuropsychological rehabilitation for mild-moderate traumatic brain
      injury.
AB  - The growing literature on cognitive rehabilitation is increasingly demanding more
      evaluation related to the validity of such therapy. The current research
      addresses some of the criticisms of previous efficacy studies and provides
      support for the effectiveness of cognitive rehabilitation according to a specific
      treatment protocol employed at an outpatient rehabilitation program. Stringent
      subject selection criterion were utilized to maximize the validity of the
      statistical comparisons of selected pre- and post- rehabilitation
      neuropsychological test scores and cognitive level of functioning. Results
      supported improvement in performance on selected neuropsychological test scores
      and cognitive functioning following cognitive rehabilitation. Limited validating
      evidence for behavioral indicators of level of cognitive functioning were
      obtained through correlations of behavioral ratings to their corresponding
      neuropsychological test scores. Results suggest that traditional measures of
      efficacy of cognitive rehabilitation may be insensitive to the cognitive sequalae
      of mild head injury due, in part, to compensatory strategies invoked by the
      subjects.

PMID- 14588431
TI  - Psychologists' accuracy in identifying neuropsychological test protocols of
      clinical malingerers.
AB  - Neuropsychology practitioners' accuracy in detecting malingering (based on
      neuropsychological test data alone) was investigated. Four test protocols had
      been produced by clinical malingerers who were identified by below-chance forced
      choice test (FCT) results. For two of the cases observation/ surveillance data
      also indicated malingering. Two test protocols had been produced by severely head
      injured individuals. Sixty psychologists reviewed a malingered test protocol and
      26 reviewed data of a head-injured patient. Error rates (diagnosis of cerebral
      dysfunction without identifying malingering) ranged from zero to 25% and averaged
      10% across the four malingered cases. Eight percent of the psychologists
      diagnosed malingering in the severely head-injured cases. Psychologists who
      received FCT data were significantly more confident in their diagnoses than were
      psychologists who did not receive FCT results, but they were not more accurate.
      The results suggest that neuropsychologists are capable of accurately detecting
      malingering, at least for obvious cases.

PMID- 14588432
TI  - Forward and backward memory span should not be combined for clinical analysis.
AB  - The practice of combining forward and backward memory span, as represented so
      prominently on the various Wechsler Scales, to arrive at a composite score for
      clinical interpretation is examined historically and actuarially using a large (N
      = 1,342) nationally stratified random sample of children from ages 5 years
      through 19 years. Past literature does not support the additive nature of forward
      and backward memory span as elements of a common process. Factor analyses of
      forward and backward recall using both digits and letters indicate that the two
      memory processes are distinct as well and should not be combined for clinical
      interpretation.

PMID- 14588433
TI  - Malingering detection with the dot counting test.
AB  - The Dot Counting Test (DCT) offers a technique for malingering detection that is
      less transparent than the forced-choice testing that has received so much recent
      attention. The present study defined six dependent variables derived from DCT
      responses, and examined these variables in the context of differentiating
      simulators from non-simulators. Four groups of subjects were studied: normal
      controls, neuropsychological evaluation patients, naive (uncoached) malingering
      simulators, and sophisticated (coached) malingering simulators. Results
      demonstrate that the DCT provides several different scores that significantly
      differ between simulators and non-simulators. The DCT appears to hold promise as
      an additional tool to neuropsychologists in the detection of malingering.

PMID- 14588434
TI  - The Ray-Osterrieth Complex Figure Test as a neuropsychological measure in
      criminal offenders.
AB  - What does the Rey-Osterrieth Complex Figure Test (CFT) measure in criminal
      offenders? This study examined neuropsychological and personality test correlates
      of performance on the Complex Figure Test in a sample of 110 incarcerated
      criminal offenders. Three standard CFT scores-copy accuracy, memory recall
      accuracy, and organizational quality-did not discriminate between violent and
      nonviolent offenders, and were not correlated with either Psychopathy Checklist
      scores or self-reported anger using the Novaco Anger Scales. CFT performance was
      significantly correlated with two other standard neuropsychological measures, a
      short form of the Category Test and the Trail Making Test. As might be expected,
      CFT scores were positively correlated with WAIS-R Block Design, and to a lesser
      extent Vocabulary. Organizational quality scores were significantly correlated
      with the Barratt Impulsiveness Scale. Approximately 27 to 36% of the variance in
      CFT scores could be explained by the combination of minority status, measures of
      nonverbal cognitive performance, and self-reported impulsivity.

PMID- 14588435
TI  - Relationship between facial discrimination and visual neglect in patients with
      unilateral vascular lesions.
AB  - This study examined the relationship between facial discrimination and visual
      neglect in patients with unilateral vascular lesions. Subjects were 85 patients
      with right- hemisphere cerebrovascular lesions and 45 patients with left-
      hemisphere cerebrovascular lesions. All were administered the Short Form of the
      Facial Recognition Test (FRT) (Levin, Hamsher, & Benton, 1975). Results revealed
      that twice as many RCVA patients (53%) exhibited impairment on the FRT as LCVA
      patients (27%). In RCVA patients, a much higher percentage of impairment was seen
      in patients with left visual neglect. Among LCVA patients, about the same
      percentage of impairment was seen in patients with right visual neglect as in
      those without neglect. WAIS-R Performance I.Q. correlated significantly with FRT
      scores in RCVA patients suggesting a relationship between facial discrimination
      and other perceptual and spatial abilities in this group. All other correlations
      between WAIS-R and FRT scores were nonsignificant.

PMID- 14588436
TI  - Validity of quick short forms of the Wechsler Adult Intelligence Scale-Revised
      with brain-damaged patients.
AB  - The validities of 41 short forms of the Wechsler Adult Intelligence Scale-Revised
      that require 20 minutes or less to give were compared in a sample of 174 brain
      damaged patients. Mean errors in predicting Full Scale IQs were computed for each
      subtest combination, and a short form efficiency index was calculated by
      correcting mean error for administration time. The three quick abbreviations
      proposed by Kaufman (1990) proved to be among the more efficient predictors of
      Full Scale IQ, but a number of other short forms also performed well. The data
      provide psychometric information for selecting a quick measure of IQ that fits
      the needs, preferences, and time constraints of the neuropsychologist.

PMID- 14588437
TI  - Word stem priming in unilateral stroke patients: word type and laterality
      effects.
AB  - We explored word type and lesion laterality effects in visual word stem
      completion priming. Participants were 24 stroke patients (12 left, 12 right) and
      11 non-brain damaged, medical controls. Participants studied 32 threatening and
      32 nonthreatening words and completed cued recall and word stem priming tasks
      (Mathews, Mogg, May, & Eysenck, 1989). Stroke groups had lower cued recall than
      controls and the right hemisphere damaged group was lower in cued recall than the
      left. Word type did not affect cued recall. Groups were comparable in word stem
      priming, and there was a word type effect such that more nonthreatening than
      threatening words were produced. No laterality effects were found in word stem
      priming. Implications for models of how words are processed during word stem
      priming are discussed.

PMID- 14588438
TI  - The neuropsychology of Kuf's Disease: a case of atypical early onset dementia.
AB  - Adult Neuronal Ceroid Lipofuscinosis (Adult NCL), also known as Kuf's Disease, is
      a rare progressive encephalopathic disease that results in dementia. This report
      describes the presentation, diagnosis, neuroanatomy, and management of Adult NCL.
      A neuropsychological case study of Adult NCL is presented, emphasizing early
      onset of psychiatric symptoms, motor involvement, and severe diffuse cognitive
      impairment. The patient's neuropsychological course is documented over a 2-year
      period, with findings interpreted within the context of current models of
      cortical and subcortical dementia. The biopsychosocial impact of misdiagnosis and
      pharmaceutical management are discussed.

PMID- 14588440
TI  - Relationship between reaction time and neuropsychological test performance.
AB  - Reaction time (RT) has been used to discriminate individuals with brain damage
      from controls, but little is known about the relationship between RT and
      neuropsychological (NP) tests. This relationship was examined 3 ways. First, the
      mean, median, and SD scores of simple and choice RT for 213 referrals were used
      as potential predictors of NP impairment in discriminant analyses; cross
      validation produced a significant hit rate. Second, the hit rate (NP impairment
      vs. no) using RT was compared to hit rates using fluency, IQ, and memory
      measures; the RT rate did not significantly exceed the others. Third, the
      abilities of RT and of a NP impairment score to classify 28 subjects into brain
      injury and control groups were compared; the hit rates were not significantly
      different. Results are interpreted to indicate moderate agreement between RT and
      NP tests regarding impairment classifications and to suggest roles for RT in NP
      assessment.

PMID- 14588441
TI  - The question of validity of neuropsychological test scores among head-injured
      litigants: development of a dissimulation index.
AB  - Two groups of 20 head-injured subjects were studied. One group was involved in
      litigation related to the head injury and the other group was not involved in
      litigation. Every subject had been tested twice, with the intertest mean interval
      for the two groups ranging from 12.00 to 14.45 months, a statistically
      insignificant difference. Two indexes of consistency of test-retest performance,
      which have been reported previously (Reitan Dissimulation Index. Comparison of
      the distributions for the two groups on the Dissimulation Index revealed no
      overlap; in fact, a gap of several points separated the groups. Every litigation
      subject performed with less consistency than any nonlitigation subject. Using an
      approach based on intra-individual test comparisons shows promise of alleviating
      the vexing problem of invalidity of neuropsychological test results.

PMID- 14588442
TI  - A clarification of the Russell, Neuringer, and Goldstein Process Key:
      implications for outcome.
AB  - The purpose of this study was that of attempting to clarify discrepant results
      regarding classificatory accuracy of the Russell, Neuringer and Goldstein (1970)
      Process Key. The Process Key is the component of the neuropsychological keys that
      classifies cases as having recently or remotely acquired brain damage on the
      basis of level of performance and severity of lateralizing signs. A correct
      classification of acute brain damage occurs when onset of illness began within 3
      months of time of testing. A study of stroke patients indicated that time since
      onset is an inadequate criterion for producing a satisfactory classificatory
      level, but time of onset in combination with type of stroke was associated with a
      high degree of classificatory accuracy. In particular, patients with recent
      thrombotic/hemorrhagic type strokes were classified as acute with a very high
      accuracy level, but the classification was substantially less accurate for recent
      stroke patients with other types of stroke, and for cases that were not of recent
      onset.

PMID- 14588443
TI  - Symptom Validity Testing of remote memory in a criminal forensic setting.
AB  - Symptom Validity Testing (SVT) has been used effectively with sensory perception
      and short-term memory. The procedure was recently adapted to assess remote memory
      for specific events. Memory for remote events is particularly important to the
      criminal justice system, and courts are beginning to draw on neuropsychology to
      assist in the assessment of claimed remote memory loss. This report discusses the
      importance of this objective technique to neuropsychologists involved with
      criminal courts and presents its use in three cases from the criminal forensic
      arena. Normative results for the three case study tests are presented and suggest
      the procedure is a robust version of SVT. Implications of these results are
      discussed.

PMID- 14588444
TI  - The effects of interference on verbal learning in multiple sclerosis.
AB  - Thirty multiple sclerosis (MS) patients were compared with 30 matched (age and
      education) controls and were asked to learn and recall 20 target words that were
      placed among 24 distracter words. Targets and distracters were printed on
      different colored cards, and the subjects were asked to read each word aloud and
      recall the target words. This task was repeated four times. The MS patients
      recalled significantly fewer words across the four trials. A second list without
      distracters was presented for two trials, and there were no significant
      differences between the groups' recall. Subsequent recall (short delay and long
      delay) for List 1 revealed significantly poorer recall for the MS group and
      significantly poorer cued recall but not recognition memory. Retrieval processes
      were implicated such as source memory, or contextual stamping, rather than
      encoding mechanisms.

PMID- 14588445
TI  - Visual reaction time and its relationship to neuropsychological test performance.
AB  - The purpose of this study was to investigate the relationship between simple and
      choice reaction time (RT) measures and neuropsychological test performance (as
      assessed by the Impairment Index of the Halstead-Reitan Neuropsychological Test
      Battery). Both median RT scores and intraindividual variability of RT scores were
      evaluated in three groups: impaired TBI, nonimpaired TBI, and normal controls. In
      all three groups, there was a statistically significant correlation between both
      reaction time measures and level of cognitive functioning. In addition, SRT,
      speed of information processing (as measured by CRT), and intraindividual
      variability of RT scores continued to be impaired in many brain-damaged
      individuals who, according to the Impairment Index, had fully recovered from
      their cognitive deficits. Median RT scores were better able to discriminate
      between impaired TBI patients and normal controls; but intraindividual
      variability of RT scores was better able to discriminate between nonimpaired TBI
      patients and normal controls. It was concluded that, by adding the two short RT
      tests to the neuropsychological test battery, more accurate predictions can be
      made about a patient's level of cognitive functioning and the nature of treatment
      needed for continued recovery.

PMID- 14588446
TI  - The problem of assessing brain damage in psychiatric samples: use of personality
      variables in prediction of WAIS-R scores.
AB  - Detection of IQ decrements due to brain injury in patients with preexisting
      psychiatric disorders was examined. Subjects included 280 male and female adult
      psychiatric patients who were free of identified neurological disorders. Subjects
      were administered the MMPI and WAIS-R. Original (Barona, Reynolds, & Chastain,
      1984) and revised (Barona & Chastain, 1986) Barona formulae were used to
      calculate premorbid IQ based on demographic variables. Multiple regression
      analyses were utilized to predict Wechsler IQ scores from the predicted Barona
      (original and revised) IQ scores along with MMPI clinical and validity scale raw
      scores for the experimental group (N = 186). The Barona equations overpredicted
      current IQ scores. The addition of MMPI variables when predicting current IQs
      resulted in significant increments in R(2)(p <.01). Cross-validation on a second
      sample (N = 94) yielded similar results when MMPI variables were added to all the
      original Barona formulae and the Barona PIQ revised formula. The MMPI may provide
      a means of incorporating pathology and personality characteristics into the
      detection of brain damage in psychiatric patients.

PMID- 14588447
TI  - Longitudinal neuropsychological effects of n-hexane exposure: neurotoxic effects
      versus depression.
AB  - Human exposure to n-hexane (a hexacarbon solvent) is relatively frequent as it is
      used in many industries as a solvent, a thinner, and a cleaning agent. This
      report examines a case of peak n-hexane exposure, involving known exposure to
      high levels over a relatively brief period of time. Peak exposure is a risk
      factor for persisting neuropsychological impairment. However, cognitive deficits
      and depression have not been measured in studies of n-hexane, and only peripheral
      neuropathy, often reversible, is thought to be the neurological risk. This case
      demonstrates the longitudinal patterns of neuropsychological functions and
      emotion, and represents the early and late developing effects of n-hexane
      exposure that parallel the longitudinal change reported in groups of workers with
      solvent exposure.

PMID- 14588448
TI  - Stability of performance on the Hopkins Verbal Learning Test.
AB  - Stability of performance on the Hopkins Verbal Learning Test (HVLT) was assessed
      in 45 healthy elderly subjects over a 9-month period. Stability coefficients were
      moderate but statistically significant for total recall (r = 0.50), true-positive
      recognitions (r = 0.66), and false-positive errors (r = 0.42). These correlations
      are comparable to test-retest correlations reported for other clinical tests of
      verbal memory (e.g., Logical Memory subtest of the Wechsler Memory Scale-Revised,
      California Verbal Learning Test) and are sufficient for its clinical use.

PMID- 14588449
TI  - The Rey-Osterreith Complex Figure Test: norms for young adolescents and an
      examination of validity.
AB  - Although recent studies have investigated theoretically relevant aspects of
      performance and psychometric properties of the Rey-Osterreith Complex Figure Test
      (ROCFT), there is no documentation of the instrument's construct and predictive
      validity in an unselected, nonclinical population. This is necessary because
      knowledge of base rates of poor performance in the general population is required
      to evaluate the significance of performance deficits in clinical populations. The
      ROCFT was administered to 740 children aged 13 years who are members of an
      unselected birth cohort, representative of the general population. Normative
      findings are presented. Correlational analysis indicated that performance on the
      ROCFT was closely related to performance on the Block Design and Object Assembly
      subtests of the WISC-R. The first documentation was obtained of the ROCFT's
      predictive validity. Subjects in an unselected nonclinical sample who had a
      history of central nervous system health problems scored below the rest of the
      sample. Implications for the continued use of this instrument are discussed.

PMID- 14588450
TI  - Malingering response styles on the memory assessment scales and symptom validity
      tests.
AB  - This study identified malingering strategies of test performance and investigated
      their presence in the responses to computer-mediated versions of Rey's Dot
      Counting and 15-Items tests, a forced-choice symptom validity procedure and the
      Memory Assessment Scales (MAS). Sixty volunteer subjects were randomly assigned
      to control (n = 30) or malingering (n = 30) groups. The control subjects were
      instructed to perform their best and the malingerers were instructed to fake a
      poor performance on the tests. As expected, malingering subjects scored
      significantly worse than control subjects on virtually all tests. Malingerers had
      slower response times on most tests. They also performed worse on recognition
      tasks in contrast to performance on recall tasks. Their response style was
      characterized by intentional wrong and random responding on recognition tasks.
      Malingerers did not show the expected worse-than-chance responding on the forced
      choice symptom validity procedure. Current tests of symptom validity may not have
      sufficient sensitivity to detect milder forms of malingering.

PMID- 14588452
TI  - Modal profiles for the Halstead-Reitan Neuropsychological Battery.
AB  - Modal profile analysis was used to cluster subjects on 11 scores from the
      Halstead-Reitan Neuropsychological Battery. The final analysis produced 18 modal
      profile types, of which 12 were replicated in multiple samples of subjects with
      differing clinical diagnoses. Subjects who had been assigned to modal types
      according to their correlations with the modal profiles were more similar to the
      centroid of their assigned groups than to the centroids of all other groups.
      Assigned subjects were eight times more likely to belong to their assigned groups
      than to any of the other groups. Fifty-four percent of subjects were assigned to
      a modal profile group according to the adopted similarity rule. Discussion
      includes a comparison of the present typology with a similar typology of Luria
      Nebraska Neuropsychological Battery profiles.

PMID- 14588453
TI  - Pre- and post-stroke MRI and neuropsychological studies in sickle cell disease: a
      case study.
AB  - The case of a patient with sickle cell disease is presented in which
      neuropsychological and magnetic resonance imaging studies were completed prior to
      and after a right hemispheric stroke. The contribution of a new MR perfusion
      technique in understanding the neurological complications in this patient is
      discussed. This case illustrates the complex pathophysiology of
      neuropsychological deficits in SCD and underscores the need to develop models
      that better reflect this complexity.

PMID- 14588454
TI  - Measurement of premorbid intellectual ability following brain injury.
AB  - Prediction of premorbid intellectual ability in brain-injured patients was
      investigated using two sets of regression equations and the Intellectual
      Correlates Scale (ICS). Eighty subjects completed the WAIS-R and the ICS. The
      four subject groups included a control group and right-hemisphere, left
      hemisphere, and diffuse brain-injured groups. As expected, brain-injured groups
      obtained lower IQs than controls. Also, estimated IQs approximated obtained IQs
      for controls, while overestimating IQs for brain-injured groups. Support was
      provided for the continued use of the Barona, Reynolds, and Chastain (1984) and
      the Barona and Chastain (1986) regression equations as measures of premorbid
      intellectual functioning. Previous findings (Schlottmann & Johnsen, 1991),
      suggesting the ICS may also serve as a measure of premorbid intellectual
      functioning, were not replicated.

PMID- 14588455
TI  - Stability of WAIS-R scatter indices in the elderly.
AB  - The test-retest reliability and clinical stability of WAIS-R VIQ-PIQ differences,
      inter, and intrasubtest scatter were investigated in a sample of 61 normal
      persons 75 years and older. The test-retest coefficient was.76 for VIQ-PIQ
      discrepancy, ranged from.05 to.56 for the intersubtest scatter range, and from.08
      to.43 for intrasubtest scatter. In terms of clinical stability, 56% of subjects
      maintained a similar magnitude and direction of meaningful VIQ-PIQ differences
      from test to retest. Classification of subtest strengths and weakness from test
      to retest was generally poor with an average disagreement of 52% from the first
      to the second assessment. Intrasubtest scatter also displayed poor clinical
      stability with 25-50% of subjects demonstrating meaningful changes on retest.

PMID- 14588456
TI  - The comparability of the WRAT-R reading test and NAART as estimates of premorbid
      intelligence in neurologically impaired patients.
AB  - A study by Wiens, Bryan, and Crossen (1993) suggests the Wide Range Achievement
      Test-Revised (WRAT-R) Reading subtest and North American Adult Reading Test
      (NAART) are adequate predictors of Wechsler Adult Intelligence Scale-Revised
      (WAIS-R) IQ scores for a normal population. Although it is common practice to use
      reading scores to estimate premorbid IQ in clinical populations, the WRAT-R and
      NAART have not been compared using individuals with brain dysfunction. The
      current study cross-validated the Wiens et al. (1993) study using neurologically
      impaired populations: traumatic brain injury (n = 118), dementia (n = 37), and
      other neurologic impairments (n = 77). The results were generally consistent
      across all three groups: (a) the WRAT-R and NAART were equivalent and accurate
      estimates of average VIQ levels; (b) the WRAT-R and NAART were equivalent but
      underestimates of higher intelligence ranges; and (c) the WRAT-R is a more
      accurate estimate for lower VIQ ranges, although both are overestimates. This
      third finding is in contrast to Wiens et al.'s (1993) results that suggest the
      WRAT-R is an accurate estimate of lower IQ ranges for normals. It is concluded
      that the WRAT-R is the preferred measure of premorbid verbal intelligence for
      psychometric and clinical reasons.

PMID- 14588457
TI  - Prediction of group membership in developmental dyslexia, attention deficit
      hyperactivity disorder, and normal controls using brain morphometric analysis of
      magnetic resonance imaging.
AB  - This study explored the utility of using selected brain morphometric indices for
      predicting group membership for children with developmental dyslexia (n = 10),
      attention deficit hyperactivity disorder: combined type (n = 10), and a control
      group (n = 10). Subjects ranged in age from 6.1 to 16 years (M = 10.5 years, SD =
      2.8). None of the subjects were diagnosed with mental retardation, nor did any of
      the subjects have a history of seizure disorder, head trauma, or other
      neurodevelopmental disorders. WISC-R Full Scale IQ ranged from 87 to 149 (M =
      114.4, SD = 13.3) with no significant differences noted between the clinical
      groups. Six brain regions, as defined by MRI scans, were selected a priori for
      inclusion in a discriminant function analysis. Reliability of the morphometric
      measures ranged from 0.94 to 0.97. One significant discriminant function was
      generated which accounted for about 61.4% of the variance between groups. The
      predictive discriminant analysis using the six morphometric MRI measurements
      classified subjects with an overall 60% accuracy with the best accuracy found for
      the developmental dyslexia and control groups. A predictive discriminant analysis
      incorporating these six morphometric measures as well as chronological age and
      FSIQ increased the overall classification accuracy to 87% with the misclassfied
      subjects assigned to one of the clinical groups. The findings support the
      presumed neurological basis for many neurodevelopmental disorders. They also
      underline the importance of including brain morphometric measures in predictive
      models.

PMID- 14588458
TI  - Screening for dementia of the alzheimer type in the community: the utility of the
      Clock Drawing Test.
AB  - This study reports the sensitivity and specificity of the Clock Drawing Test
      (CDT) for detecting dementia of the Alzheimer type in a community-dwelling sample
      of elderly subjects. Forty-two patients with clinically diagnosed Alzheimer's
      disease and 237 cognitively intact subjects were administered the CDT as part of
      an epidemiological study of aging and dementia. Three individual measures of
      clock drawing performance (quantitative score, qualitative score, and combined
      quantitative and qualitative score) were determined for each participant. When
      qualitative elements such as errors and strategies were incorporated into the CDT
      score, the sensitivity was 84% and the specificity was 72%. The findings suggest
      that a CDT score which evaluates qualitative and quantitative features provides
      reasonably good discrimination between normal elderly individuals and DAT
      patients. However, the CDT appears to have limited utility as a single screening
      instrument in the community. Instruments such as the Dementia Rating Scale
      (Mattis, 1976) provide better discrimination of DAT, indicating that functions
      such as memory and verbal fluency need to be assessed during screening.

PMID- 14588459
TI  - Fractionating frontal lobe functions: factors of the Milwaukee Card Sorting Test.
AB  - The Milwaukee Card Sorting Test (MCST), a modification of the Wisconsin Card
      Sorting Test (WCST), was administered to 71 geriatric, orthopedic or neurologic
      patients. The MCST requires that participants verbalize prior to sorting, thus
      enabling quantification of separate, elemental executive abilities needed for
      card sorting performance. A preliminary factor analysis yielded three factors,
      corresponding to elemental executive abilities of forming, maintaining, and
      switching mental set. Results are discussed as they apply to understanding the
      cognitive structure of card sorting tasks to revealing different performances
      associated with behaviorally distinct executive deficits, and to suggesting
      anatomical substrates underlying the three factors.

PMID- 14588685
TI  - Validation of the General Neuropsychological Deficit Scale with nondisabled,
      learning-disabled, and head-injured young adults.
AB  - This study examines the validity of Reitan and Wolfson's General
      Neuropsychological Deficit Scale (GNDS). The GNDS differentiated nondisabled,
      learning-disabled, and head-injured young adults matched for FSIQ with greater
      accuracy than Halstead's Impairment Index.

PMID- 14588686
TI  - The factor structure of the Wechsler Memory Scale-Revised and several brief
      neuropsychological screening instruments in recently detoxified substance
      abusers.
AB  - The Wechsler Memory Scale-Revised (WMS-R) has attracted a fair amount of research
      activity since its publication. Much of this activity has centered on the factor
      structure of the WMS-R. The present study examines the factor structure of the
      WMS-R, both when the indices are used as variables and when the scale scores
      themselves are used as variables. Three hundred fifty-two recently detoxified
      substance abusers were used as subjects. Both sets of analyses included other
      neuropsychological variables in order to facilitate clear explications of
      memorial and cognitive functions tapped by the WMS-R. The results indicate
      support both for use of the indices and for use of the subscale scores.
      Differences between these results and the results of earlier factor analyses are
      discussed in terms of sample characteristics.

PMID- 14588687
TI  - Use of the Booklet Category Test to assess abstract concept formation in
      schizophrenic disorders.
AB  - The relationship of concept formation abilities to the presence or absence of
      delusions in schizophrenic disorders was investigated. Twenty-six schizophrenic
      patients and 14 normal individuals were administered a short form of the Booklet
      Category Test (BCT). Patients were grouped into those with and without delusions.
      It was hypothesized that the delusional group would perform significantly better
      on the BCT (obtain lower error scores) than the nondelusional group. Normal and
      delusional groups obtained significantly lower BCT error scores than the
      nondelusional group, even when differences in IQ scores were statistically
      partialled out. The two schizophrenic groups also differed significantly on BCT
      error scores with the delusional group performing better than the nondelusional
      group.

PMID- 14588688
TI  - Children's color trails.
AB  - Color Trails for Children was developed in response to the need for instruments
      which minimize cultural bias in neuropsychological testing. The test, similar in
      format to Trail Making, was designed to provide an evaluation of speeded
      visuomotor tracking while minimizing the influence of language. The present
      research involves two exploratory studies which examine the relationship between
      Color Trails for Children and Trail Making, factors that may affect performance
      times, and discriminant validity. Results indicate that the tests appear to
      measure the same neuropsychological domains, and administration of Trail Making
      did not significantly alter performance times on Color Trails. Increasing age and
      IQ were related to quicker completion time for both tests. Females were found to
      complete Color Trails 2 and Trail Making Part B more quickly than males in this
      sample. Comparison between children diagnosed with learning disabilities,
      attention deficits, or mild neurological conditions and a preliminary
      standardization sample supported the discriminant validity of Color Traits to
      distinguish between normal controls and children with altered neuropsychological
      functioning. Comparison between clinical conditions indicated that Color Trails 2
      was particularly sensitive in discriminating among the groups. Although further
      research is needed, results suggest that Color Trails has the potential to be an
      effective research and clinical tool in child neuropsychological assessment.

PMID- 14588689
TI  - Predicting WAIS-R IQ premorbid ability: combining subtest performance and
      demographic variable predictors.
AB  - The WAIS-R standardization sample was used to develop regression formulas
      designed to predict WAIS-R IQ scores. In contrast to previous approaches that
      focused on either "hold" measures or demographic variables as predictors of
      premorbid functioning, these two domains were used conjointly in the present
      study. WAIS-R subtests served as measures of present ability, whereas age, race,
      sex, education, and occupation served as the demographic predictors. Because any
      WAIS-R subtest may be impaired following brain injury, no subtest(s) were
      determined a priori to be "hold" measure(s). Instead, 33 regression formulas were
      developed each combining 1 of the 11 WAIS-R subtests with demographic variables,
      to predict IQ scores. The current equations generally doubled the amount of
      variance accounted for by demographic variables alone and accounted for more
      variance in WAIS-R IQs than any other currently available method of predicting
      premorbid cognitive functioning. Regression to the mean was not a significant
      problem. The regression equations are reported to aid in the estimation of
      premorbid WAIS-R IQ. Tables of predictive accuracy are also presented.

PMID- 14588690
TI  - Practice effects with the NIMH AIDS abbreviated neuropsychological battery.
AB  - The degree of practice effects with the Brief NIMH Neuropsychological Battery for
      HIV Infection and AIDS is reported using a 7-10 day test-retest interval. The
      patient groups were asymptomatic and symptomatic of HIV while the control group
      was made up of "at risk" volunteers. Statistically significant practice effects
      were obtained on the California Verbal Learning Test, the Paced Auditory Serial
      Addition Task and the Visual Search Test among the infected individuals. The
      controls subjects demonstrated statistically significant practice effects on all
      of the neuropsychological tests. The implications of these findings in
      prospective studies are discussed.

PMID- 14588691
TI  - Evaluation of an efficient method for verifying higher educational credentials.
AB  - Neuropsychologists do not routinely verify patient's self-reported educational
      information. The present investigation attempted to validate a procedure for
      verifying educational credentials by phone. Of the 50 subjects representing 38
      colleges that participated in this study, the attainment of baccalaureate degrees
      of only 6% could not be immediately verified by phone. All 19 schools given
      fictitious information reported they had no record of the fictitious student's
      attendance. The results of this study suggest that telephoning is an efficient
      method for verifying higher educational credentials. The authors recommend
      routine screening of patients whose academic credentials are questionable.

PMID- 14588692
TI  - A qualitative analysis of semantic intrusive errors in Alzheimer's disease.
AB  - Intrusive or perseverative errors as evidenced on tests of memory have been found
      to occur with greater frequency in patients with Alzheimer's Disease (AD)
      relative to other disorders and are thought to reflect the cholinergic deficits
      associated with AD. A particular type of intrusive error, semantic intrusions,
      has been found to discriminate AD from multi-infarct dementia and normal elderly
      controls. However, it has been suggested that such errors actually reflect random
      responding as the result of the disinhibition often observed in AD patients. The
      present study compared the frequency and types of intrusive errors from a sample
      of mildly, moderately, and more severely impaired AD patients who had undergone
      the Fuld Object Memory Evaluation with the "guesses" of elderly controls. Results
      of this study indicate that the semantic intrusions of AD patients differ both in
      type and frequency from the guesses of the control subjects.

PMID- 14588693
TI  - A psychometric analysis of the California Card Sorting Test.
AB  - The purpose of this study is to begin to characterize performance on the
      California Card Sorting Test (CCST), a relatively new measure of executive
      function specifically designed to fractionate problem-solving ability into its
      cognitive components. Data describing the performance of 135 neurologically
      intact young adults on the CCST and four other common measures of executive
      function are presented. Factor analyses indicated that the CCST is a valid
      measure of concept formation and abstract ability and that the CCST taps
      abilities different from those measured by commonly used tests of executive
      function. While further work must be done, the CCST seems to hold promise as a
      neuropsychological assessment instrument.

PMID- 14588694
TI  - Neuropsychological complaint base rates in personal injury, revisited.
AB  - Recent research supports the need for consideration of neuropsychological base
      rate phenomena in personal injury claimants. This response describes the utility
      of a preinjury versus postinjury procedure for alleviating possible false
      positive errors in postinjury behavioral symptoms, while concurrently minimizing
      likelihood of false negative errors.

PMID- 14588901
TI  - Hippocampal adequacy versus functional reserve: predicting memory functions
      following temporal lobectomy.
AB  - While decrements in memory following temporal lobectomy for intractable epilepsy
      remain a major neurocognitive complication of surgical intervention, it has been
      difficult to identify patients who are most at risk for developing decrements in
      their memory functions following surgery. Two different models of hippocampal
      functioning have been posited to account for postsurgical memory losses:
      hippocampal reserve versus functional adequacy. This article briefly examines the
      basis of the traditional model of hippocampal reserve, which suggests that it is
      the reserve or capacity of the contralateral hippocampus to support memory after
      surgery that determines whether changes in memory function will be observed. A
      more in-depth review of emerging data from studies of function (baseline
      neuropsychological testing and intracarotid amytal procedure) and structure
      (histologic cell densities and MRI volumetrics) supporting a functional adequacy
      model of hippocampal functioning is then presented. Data from these latter
      studies provide strong convergent support for the view that the risk for memory
      decrements following mesial temporal lobe epilepsy surgery is inversely related
      to the functional adequacy of the tissue to be resected. Data reviewed here have
      broad implications for the field of neuropsychology. Not only do the data
      reported in this article challenge some of the basic tenets of our understanding
      of the role of the hippocampus in memory functioning, but they illustrate the
      importance of ongoing research, critical reevaluation of basic concepts, and the
      importance of self-scrutiny in light of new technologies.

PMID- 14588902
TI  - Integrating neurobiological, psychosocial, and behavioral paradigms: a
      transactional model for the study of ADHD.
AB  - This article reviews neurobiological, psychological, behavioral, and social
      interactional paradigms for the study of attention deficit hyperactivity
      disorders (ADHD). An integrated model for the assessment, diagnosis, and
      treatment of ADHD will be explored. Because the controversy among these
      approaches remains vigorous today, a review of the literature provides a context
      for why these theories should be integrated. Whereas it will be argued that each
      paradigm offers unique information that adds significantly to advancing a science
      of childhood disorders, an integrated model provides a vehicle necessary for the
      study and understanding of ADHD.

PMID- 14588903
TI  - Construct validity of the WCST in normal elderly and persons with Parkinson's
      disease.
AB  - Separate principle component analyses of the WCST were conducted on 187 normal
      elderly and 181 persons with Parkinson's disease (PD). Adequate construct
      validity was found for "conceptualization/problem solving" and "failure to
      maintain set" factors in both groups. Perseverative and nonperseverative errors
      were related for the normal group, but not for the PD subjects. This may reflect
      the frontal systems deficit observed in PD. Additional principle component
      analyses were conducted with the WCST and measures of memory and attention. In
      neither the normal nor the PD group did the WCST significantly load with the
      memory and attention measures. This suggests that the WCST provides information
      about problem solving relatively independent of memory and attention functions
      for elderly persons.

PMID- 14588904
TI  - A procedure for assessing storage and retrieval on the Wechsler Memory Scale
      Revised.
AB  - A methodology to assist in distinguishing deficient memory storage from
      compromised retrieval operations is presented for use with the Logical Memory
      (LM) and Visual Reproduction (VR) subtests of the Wechsler Memory Scale-Revised
      (WMS-R; Wechsler, 1987). A 21-item five-option multiple choice recognition test
      for LM and a cuing technique for VR are presented, followed by descriptive data
      based on a sample of 94 psychiatric inpatients (mixed diagnoses) and a sample of
      99 brain-injured (BI) patients. The BI sample performed worse than the
      psychiatric sample on all of the LM and VR measures, with VR-CUED showing the
      highest degree of discrimination. In both groups, many subjects initially
      acquired much more information than they reported during the standard free recall
      format. The supplemental scoring format and reference data reported herein
      provide clinically useful information regarding a person's ability to store and
      access new information.

PMID- 14588905
TI  - Neurological soft signs in schizophrenia: are they related to negative or
      positive symptoms, neuropsychological performance, and violence?
AB  - This investigation was carried out on 31 unemployed schizophrenic outpatient men.
      The general purpose was to explore new aspects of neurological soft signs in
      schizophrenia. A 108-item version of the Nathan Kline Institute scale of soft
      signs, the Schedule for Affective Disorders and Schizophrenia psychiatric
      interview, the negative and positive symptom scale (PANSS), a comprehensive scale
      of life-time history of violence, and a large set of neuropsychological tests
      were administered. It was found that "motor" soft signs were significantly more
      prevalent than "sensory-perceptual" signs, but that each body side manifested
      equal numbers of neurological signs. Before and after statistical correction for
      age, education, alcoholism, drug abuse disorder, and daily and cumulative
      neuroleptic dosage, orbitofrontal-type neuropsychological tasks measuring
      "impulsivity" related very robustly to the soft signs. Furthermore, before and
      after the same statistical corrections, right body-side signs correlated
      significantly with the same neuropsychological tests, whereas left body-side
      signs did not. The PANSS scores and levels of lifetime violence generally did not
      correlate significantly with neurological soft signs. The latter negative
      findings, we think relate to the fact that these were relatively high-functioning
      (i.e., outpatient) schizophrenics. Overall, the results support notions of
      frontal lobe and left hemisphere involvement in schizophrenia, these two
      dysfunctional systems being apparently linked at the level of the orbitofrontal
      area of the brain.

PMID- 14588906
TI  - Poppelreuter-Ghent's Overlapping Figures Test: its sensitivity to age, and its
      clinical use.
AB  - This study aims to identify the cognitive variables involved in a task of visual
      recognition of meaningful and meaningless two-dimensional line-drawings of
      shapes; the Poppelreuter-Ghent Overlapping Figures Test. It was found that the
      performance of healthy controls was influenced by age and education, but not sex.
      Age and education adjusted norms are set forth. Meaningful patterns were better
      recognised than meaningless ones. Number of overlapping patterns, direction, and
      degree of rotation were among the other variables considered. Only the latter
      variable significantly influenced the difficulty of the task. The clinical use of
      this test was verified on clinical populations of patients affected by
      Alzheimer's disease and right or left hemisphere damage. Left hemisphere damaged
      patients did not show deficits. Alzheimer and right hemisphere damaged patients
      were impaired and the degree of rotation significantly influenced their
      performance. In conclusion, the Poppelreuter-Ghent's Test is a multicomponential
      task, the visuo-spatial components of which were shown to be the most important.

PMID- 14588907
TI  - The determination of clinically meaningful cognitive decline: development and use
      of an alternative method.
AB  - Statistical methods traditionally used in the analysis of change (e.g., repeated
      measures ANOVA) may be inadequate for the investigation of cognitive decline if a
      study's effect size is small, the variance within groups is heterogeneous, or the
      statistical power is low. To examine an alternative approach to the determination
      of clinically meaningful cognitive decline and investigate whether such decline
      occurs during the first year after stroke, we administered a neuropsychological
      test battery to 172 patients (age = 70.3 +/- 7.6 years; education = 10.3 +/- 4.7
      years) 3 and 12 months after stroke and 199 nondemented stroke-free control
      subjects (age = 71.1 +/- 6.4 years; education = 12.8 +/- 4.2 years) on two
      occasions 12 months apart. Two neuropsychologists classified each subject's test
      performance as having declined, improved, or remained stable based solely on
      clinical judgment. Reliability of the rating of decline versus the pooled rating
      of improvement/stability was excellent (kappa = 0.79). The two rating groups
      differed significantly and in the appropriate directions in change on most tests.
      While a MANOVA comparing the stroke and control groups on change in test scores
      was not significant, logistic regression analysis determined that a rating of
      clinically meaningful cognitive decline was associated with stroke status (Odds
      Ratio = 1.8, 95% Confidence Interval = 1.0 to 3.2), while adjusting for
      demographic factors. We propose that this alternative approach to the analysis of
      cognitive change can facilitate the recognition of decline in subgroups of
      subjects. It would be valuable as an adjunct to studies of the incidence of
      dementia, for example, in which the recognition of cognitive decline might be
      difficult in highly educated patients whose baseline level of performance is far
      above the cutoffs operationalized for the diagnosis of dementia.

PMID- 14588908
TI  - Visuoconstructive deficit following infarction in the right basal ganglia: a case
      report and some experimental data.
AB  - Visuospatial disorders are typically described as a consequence of right
      hemisphere, cortical lesions. We report the case of a female with
      visuoconstructive deficits with an infarct in the right basal ganglia, with no
      evidence of visual field defect, hemi-inattention, or sensory or motor loss.
      Using a process approach to obtain additional quantitative data, we showed that
      her visuoconstructive disorder could not be attributed to a defect in visual
      perception, per se. All other aspects of her neuropsychologic skills were normal.
      These findings provide additional support for the role of subcortical structures
      in spatially-related motor function and for the utility of applying experimental
      techniques to clarify the nature of deficits.

PMID- 14588909
TI  - A case of bilateral thalamic lesions with anterograde amnesia and impaired
      implicit memory.
AB  - Thalamic nuclei appear to play an important role in memory functioning. Severe
      anterograde amnesia has been reported with lesions of the dorsomedial and
      anterior nuclei and their connections. We report the case of a woman with
      discrete thalamic lesions involving the anterior and dorsomedial nuclei who had a
      persistent anterograde amnesia. Contrary to a previous case report describing
      impairment only with explicit memory, this patient had impairment with both
      implicit and explicit memory. This case is discussed in terms of the relevant
      literature associating the diencephalon, amnesia, and implicit memory.

PMID- 14588910
TI  - Recommendation for test administration in litigation: never administer the
      category test to a blindfolded subject.
AB  - Fox (1994) purports to determine the appropriateness of the normative data for
      the Logical Memory subtest of the Wechsler Memory Scale-Revised for individuals
      in litigation and suggests that "...many of these people would have been
      incorrectly diagnosed as having a neuropsychological problem that did not exist."
      His data do not support such a conclusion, but rather appear simply to
      demonstrate that patients in litigation concerning potentially painful orthopedic
      and/or emotional injuries can, as a group, perform slightly below average levels
      on memory tests.

PMID- 14588911
TI  - Age changes on tests of fluid and crystallized ability for women and men on the
      Kaufman Adolescent and Adult Intelligence Test (KAIT) at ages 17-94 years.
AB  - Within a norm sample of 1,500 men and women, 17-94 years of age (13 age
      groupings), using Multivariate Analysis of Variance and Covariance, it was found
      that four measures designed to indicate fluid reasoning (Gf) and the composite
      measure of Gf declined steadily over the entire adulthood period, the decline
      accelerating during the period beginning at about age 55 years. Also, four
      measures of crystallized knowledge (Gc) and the composite measure of Gc increased
      through the 20s, neither increased nor decreased through mid-adulthood until
      about age 60 years, and declined thereafter. For the composite measures of Gf and
      Gc, there were no main effects or interaction effects associated with Gender.
      When educational attainment was covaried, small but statistically significant
      Gender main effects were found for four of the subtest measures of Gf and Gc;
      significant Gender x Age interaction effects were found for two subtests.
      Interpreted within Gf-Gc theory, the results replicate and extend evidence of the
      adulthood development of cognitive capabilities.

PMID- 14588912
TI  - Effects of prior testing with the WAIS-R NI on subsequent retest with the WAIS-R.
AB  - Seven subtests from the Wechsler Adult Intelligence Scale, Revised as a
      Neuropsychological Instrument (WAIS-R NI) were administered to 20 nonreferred
      university students. The same participants were administered the corresponding
      subtests from the WAIS-R 3 to 4 weeks later. Data concerning amount and
      consistency of change in 'scaled scores' were compared to those reported by
      Wechsler (1981) for test-retest with the WAIS-R. Performance on standard items
      was also compared to performance on multiple choice items from the WAIS-R NI.
      Gains observed in subtest 'scaled scores' at retest were comparable to those
      reported by Wechsler (1981). A substantial minority of participants obtained
      lower scores on some multiple choice items than they did on corresponding
      standard items. Implications and limitations of the current data, and the
      pressing need for comprehensive normative data for the WAIS-R NI are discussed.

PMID- 14588913
TI  - Validity of short forms of the intermediate Halstead Category Test in children
      with traumatic brain injury.
AB  - The validities of three of Reeder and Boll's (1992) short forms of the
      intermediate version of the Halstead Category Test (IHCT) were evaluated in a
      sample of 87 children with traumatic brain injury. All three short forms had
      acceptable relationships with length of coma. A short form that was based on the
      first 15 items of every IHCT subtest appeared to be relatively superior to the
      other forms in terms of discriminating between groups of mild/moderate vs. severe
      injuries. It was concluded that this short form may be an accurate and valid
      alternative to the full-length IHCT in children with traumatic brain injury.

PMID- 14588914
TI  - Cognitive-behavioral prevention of postconcussion syndrome.
AB  - The symptoms of postconcussion syndrome (PCS) are persistent, and no empirically
      tested treatment is available. The treatment group (n = 29) in this study
      received a printed manual and met with a therapist prior to hospital discharge to
      review the nature and incidence of expected symptoms, the cognitive-behavioral
      model of symptom maintenance and treatment, techniques for reducing symptoms, and
      instructions for gradual resumption of premorbid activities. The control group (n
      = 29) received routine hospital treatment and discharge instructions. Both groups
      had sustained mild head injuries characterized by Glascow Coma Scale scores of 13
      15 on admission without any measurable period of posttraumatic amnesia. Group
      assignment was random. Groups did not differ significantly on age, Glascow
      scores, litigation status, gender, or initial number of PCS symptoms. Patients
      were contacted 6 months following injury by an interviewer who was unaware of
      group assignment to obtain outcome data. Treated patients reported significantly
      shorter average symptom duration (33 vs. 51 days) and significantly fewer of the
      12 symptoms at followup (1.6 vs. 3.1). Subjects were also asked how often each
      symptom had occurred in the previous week, and how severe the symptom typically
      was. The treatment group experienced significantly fewer symptomatic days (.5 vs.
      1.3) and lower mean severity levels. Results suggest that brief, early
      psychological intervention can reduce the incidence of PCS.

PMID- 14588915
TI  - Attentional performance of children with traumatic brain injury: a quantitative
      and qualitative analysis of digit span.
AB  - Previous studies have indicated that digit span performance is not particularly
      sensitive to the effects of traumatic brain injury (Baddeley & Warrington, 1970;
      Brooks, 1975; Sterne, 1969). However, clinical lore posits poorer backward vs.
      forward performance compared to normals due to the greater attentional demands of
      the backward task. This study examined qualitative aspects of Digit Span
      performance including forward/backward span discrepancies and error patterns in
      children with traumatic brain injury (n = 20) and normals (n = 19). The
      hypothesis of greater forward/backward discrepancy with traumatic brain injury
      was not supported. Children with traumatic brain injury make a significantly
      greater number of preceiling errors than normals, consistent with other findings
      of increased performance variability. Preceiling errors are errors that occur in
      trials prior to the two failed trials, resulting in discontinuation of the task.
      In addition, cognitive correlates of error types, such as WISC-R factor scores,
      were significantly different between groups. The results of this study suggest
      that a more detailed analysis of performance on attentional tasks previously
      described as resilient to brain injury may shed further light on the nature of
      acquired attentional deficits.

PMID- 14588916
TI  - An interrater reliability study of the Luria-Nebraska Neuropsychological Battery
      Form-II quantitative scoring system.
AB  - This study provides information on the interrater reliability of the quantitative
      scoring system of the Luria-Nebraska Neuropsychological Battery Form II (LNNB
      II). The accuracy of each rater following a training procedure was also
      evaluated. Six college students served as raters, and participated in a 20-22
      hour training procedure. This training procedure utilized a protocol similar to
      one used in previous interrater reliability studies performed with Form I.
      Following the training procedure, raters were asked to score two videotaped LNNB
      II administrations in which a confederate portrayed test performance that was
      relatively straightforward to score, as well as more ambiguous test performance.
      Excellent interrater agreement and accuracy were found on the quantitative
      scoring on both tapes. Implications for training in administration and scoring
      are discussed.

PMID- 14588921
TI  - Neuropsychological features of diffuse Lewy body disease.
AB  - A case of a 60-year-old man with biopsy-proven diffuse Lewy body disease was
      presented with clinical and serial neuropsychological data. Findings showed a
      rapid decline over a 2-year period characterized by an atypical degenerative
      dementia, including a global mental decline with preserved orientation, profound
      perceptual deficits, and no specific relative progressive memory impairment. Few
      extrapyramidal signs were noted, but subtle visual hallucinations and vivid
      nightmares occurred throughout the course. He underwent an experimental trial of
      tacrine, but showed an adverse reaction. Of the few detailed neurocognitive case
      descriptions of this disease found in the literature, this article highlights the
      unique variability and clinical manifestations that differentiate this disorder
      from the dementia of the Alzheimer's type.

PMID- 14588922
TI  - A brief assessment of executive control dysfunction: discriminant validity and
      homogeneity of planning, set shift, and fluency measures.
AB  - The current study evaluated the discriminant validity and homogeneity of category
      fluency, Stroop interference, and planning measures of executive dysfunction and
      introduced a new measure of planning behavior. We compared performance of
      patients with schizophrenia, Parkinson's disease, and Huntington's disease, which
      are disorders associated with some impairment of executive function. Findings
      indicated that all three measures successfully discriminated between patient
      groups and controls. Correlational analysis suggested a strong association
      between test scores on these measures, which were only moderately related to
      performance on nonexecutive function measures. It is concluded that the three
      tasks are sensitive and relatively homogeneous in their recruitment of executive
      functions.

PMID- 14588923
TI  - Further analyses of clock drawings among demented and nondemented older subjects.
AB  - In a previous article we described a 10-point scoring system (i.e., scale 1) to
      grade clock drawings to command and copy with hands set for "ten after 11" among
      demented patients. Alzheimer's subjects (AD) improved from the command to copy
      conditions, whereas subjects with ischaemic vascular dementia (IVD) did not. To
      investigate the underlying cognitive deficits responsible for this profile, an
      additional scale was developed (scale 2) that tallied errors in graphomotor
      functioning, hand/number placement, and executive control. On an independent
      sample of subjects, AD subjects, again, made significant improvement on scale 1
      from the command to copy condition, whereas no such improvement occurred among
      the IVD subjects. On scale 2, IVD subjects made more graphomotor errors in the
      command condition, and more executive control and more total errors in the copy
      conditions than AD subjects. A number of positive correlations were noted between
      tests of language and memory on scale 1. By contrast, scores on tests of
      executive control declined as scale 2 errors increased. In addition, a principal
      component analysis indicated that scale 2 test performance loaded on a factor
      with other tests related to executive control. These results suggest that
      impairment in frontal systems functioning may explain why IVD subjects do not
      improve from the command to copy conditions on scale 1. Such a pattern of
      performance in clock drawing may also be helpful in making a differential
      diagnosis between AD and IVD.

PMID- 14588925
TI  - The role of attention in Wisconsin Card Sorting Test performance.
AB  - The present study sought to test the hypothesis that the second factor
      (consisting of Failure-to-Maintain-Set and other scores) found in two recent
      factor analyses of the Wisconsin Card Sorting Test reflects attentional function.
      The effect of color overlays (an experimental manipulation known to influence
      neural systems linked to attention) was examined in 17 normal control and 14
      attention-disordered children (ages 8 to 12). Group and Color main effects were
      found for Factor 1 (which consists largely of measures of perseveration) and a
      Color main effect was observed for Factor 2. The Color effect for Factor 2
      supported the contention that this factor reflects attentional processes. A
      hypothesis concerning the relationship between problem solving and attention on
      the WCST is offered and a means for testing it is discussed.

PMID- 14588924
TI  - WAIS-R verbal-performance IQ discrepancies in persons with lateralized lesions:
      utility of a seven subtest short form.
AB  - WAIS-R Verbal-Performance IQ difference scores for Ward's (1990) seven subtest
      short form and the complete WAIS-R were examined in patients with lateralized and
      diffuse lesions. For both versions, the expected Performance > Verbal pattern was
      observed in the right hemisphere lesion group, while no summary score differences
      were seen in the left hemisphere group. Verbal-Performance IQ discrepancies for
      the short form fell within +/- 5 points of the WAIS-R discrepancy scores in about
      75%of the cases, regardless of lesion location. Statistically reliable IQ
      differences between the complete and abbreviated WAIS-R attained 66%, 91%, and
      89% agreement for the left, right, and diffuse groups, respectively. The results
      support the clinical utility of the seven subtest short form.

PMID- 14588926
TI  - Laterality differences in quantitative and qualitative Hooper performance.
AB  - The Hooper Visual Organization Test (HVOT) is a measure of visuospatial
      processing commonly employed in neuropsychological assessment. Despite the well
      documented relationship between visuospatial abilities and right hemisphere
      function, the literature has not supported a right hemisphere association with
      HVOT performance. The current study was conducted to examine laterality
      differences in HVOT performance. Sixty-seven geriatric stroke patients (44 right
      CVAs, 23 left CVAs) were administered the HVOT and the Mini-Mental State Exam
      (MMS). Results revealed significant differences between CVA groups for total
      score, with right CVA patients performing more poorly. Qualitative error analyses
      revealed highest frequencies for part responses and don't know/no response
      errors. Between-group differences were seen for part and unformed/unassociated
      errors (higher right CVA rates), and language-based errors (higher left CVA
      rates). Findings are consistent with theories of brain lateralization and suggest
      that whereas HVOT performance predominantly involves right hemisphere functions,
      left hemisphere dysfunction may also lead to impaired performance, and the two
      can be discriminated by qualitative analysis of errors.

PMID- 14588927
TI  - The differential effects of simulating malingering, closed head injury, and other
      CNS pathology on the Wisconsin Card Sorting Test: support for the "pattern of
      performance" hypothesis.
AB  - We investigated the effects of faking bad on the Wisconsin Card Sorting Test,
      comparing the performance of simulating malingerers (M; n = 24) to controls (C; n
      = 21), closed head-injured patients (CHI, n = 70), and patients with mixed CNS
      pathology other than CHI alone (CNS; n = 89). Stepwise discriminant functions
      achieved good accuracy (91-96%), sensitivity (58-100%), and specificity (92-100%)
      in differentiating simulating malingerers from these groups. The Categories score
      was a consistent significant independent discriminating variable. Categories
      alone could differentiate between the M and C groups. However, in discriminating
      between simulating malingerers and both CHI or CNS patients, more complex
      patterns of performance emerged, consisting of relatively poorer performance
      ratios on Categories compared to Perseverative Errors. This supported the Pattern
      of Performance theory of the effects of simulating malingering on
      neuropsychological tests, which holds that people simulating malingering do more
      poorly on obvious vs. subtle tasks compared to people with verified brain damage.
      Due to the difficulty of tracking one's performance on several different indices
      simultaneously, known patterns of performance for patients with verified brain
      dysfunction should be very difficult to fake, even with coaching.

PMID- 14588931
TI  - National Academy of Neuropsychology Distinguished Neuropsychologists Award
      address. Slouching toward the milennium: some survival prescriptions for
      neuropsychology.
AB  - The following address was given as the Distinguished Neuropsychologist Award
      Presentation and Acceptance Speech at the 15th annual conference of the National
      Academy of Neuropsychology, San Francisco, November 2, 1995. Substantive issues
      discussed include: (a) the threatened loss of the clinical in clinical
      neuropsychology; (b) post-doctoral training and job market dilemmas in 1995; (c)
      proficiency versus specialty status for neuropsychology; (d) the Battle of the
      Boards (ABCN, APBN); and (e) forensic neuropsychology, a cautionary note.

PMID- 14588932
TI  - Identification of malingered head injury on the Halstead-Reitan battery.
AB  - Heaton et al. (1978) demonstrated that the performance of malingerers and actual
      head trauma patients could be distinguished on the HRB by discriminant analysis.
      The present study replicated Heaton et al.'s methodology on a larger sample to
      provide a more stable function for discriminating simulated and real head trauma.
      Malingerers (n = 80) were instructed to fake severe deficits without being
      obvious. Patients (n = 80) had documented trauma and were not litigating for
      compensation. Groups were matched on age, gender, and overall Impairment Index to
      permit comparisons between patterns of performance. A crossvalidated step-wise
      discriminant function correctly identified 88.75% of the groups, with 83.8% true
      positives and 93.8% true negatives. This function was applied to several
      published data sets. Both malingerer and patient groups were accurately
      identified in Heaton et al. (1978) and Trueblood and Schmidt (1993). Faust et
      al.'s (1988) adolescent malingerer and the malingered performance of three
      litigating patients published by Cullum et al. (1991), were also correctly
      classified.

PMID- 14588933
TI  - Comparison of multiple scoring methods for Rey's malingered amnesia measures.
AB  - The predictive accuracy of Andre Rey's malingered amnesia measures (Memory for
      Fifteen Items and Word Recognition List) was examined. Discriminant function and
      crosstabulation analytic strategies were applied to predict membership in either
      a traumatically brain injured group (n = 60) or in a litigated minor head injury
      group claiming permanent severe disability (n = 90). Satisfactory hit rates were
      achieved with Rey's original scoring methods, but improved hit rates were
      obtained with scoring modifications. Removal of dense amnesiacs from the sample
      resulted in even better hit rates. Rey's measures appear to be valid for the
      assessment of cognitive malingering in settings where litigated disability claims
      are out of proportion to injury characteristics. Rey's measures are not
      appropriate for globally and severely impaired patients in clinical settings.

PMID- 14588934
TI  - Evidence of a neurologically based "denial of illness" in patients with
      Huntington's disease.
AB  - Patients diagnosed with Huntington's Disease (HD) commonly show a denial of
      symptoms and an unawareness of the motoric, cognitive, and emotional changes that
      accompany this disease. To examine if this denial has a neurological component to
      it, 19 patients who received a positive diagnosis of HD from the presymptomatic
      HD clinic at the University of Connecticut Medical School, and 14 consecutive
      patients referred for neuropsychological testing with nonHD diagnoses, were
      administered a simple, eight-item self-report test that asked them to rate their
      cognitive and motoric abilities. Two staff members, both of whom met with the
      patients and were familiar with the neuropsychological test results, similarly
      rated the patients' deficits. HD patients were then divided into "high" (HA) vs.
      "low" (LA) anosognosia groups based on differences between their self-ratings and
      staff ratings, and given a neuropsychological battery. Correlation's between the
      two investigators found that the eight-item scale was highly reliable across
      investigators (R =.89). HD patients were significantly different from controls in
      their self-rating of their own capabilities in comparison to staff ratings (p
      <.05). ANOVA found the HA HD patients to be impaired relative to the LA HD group
      on a number of neuropsychological measures, including the Wisconsin Card Sorting
      Test and various measures pertaining to visual-spatial ability on the Wechsler
      Adult Intelligence Scale-Revised. These findings suggest that a component of the
      "illness denial" that HD patients exhibit, and that traditionally have been
      attributed to "psychodynamic" factors, likely have a neurological component to
      them. Implications of these findings for teams who are preparing to provide
      anosognostic HD patients with positive results regarding their HD workup is
      discussed.

PMID- 14588935
TI  - Differential relationships of age and education to WAIS subtest scores among
      brain-damaged and control groups.
AB  - The 11 subtests of the WAIS were compared to the attribute variables of age and
      education in a brain-damaged group and a non-brain-damaged (control) group.
      Because of the validity information available for the WAIS, the subtests for the
      WAIS rather than the WAIS-R were studied. Data analyses compared the level of age
      and education (each group subdivided at the median) on WAIS subtest scores and
      the correlations between attribute variables and subtest scores. The results
      revealed a number of differences between the two groups, with age and education
      having a weaker and less consistent relation to WAIS subtest scores in the brain
      damaged group than in the control group. The findings suggest that the
      relationships between attribute variables and psychological test scores are
      complex, and that adjusting or transforming raw scores for brain-damaged subjects
      according to tables based upon non-brain-damaged subjects may produce erroneous
      data.

PMID- 14588936
TI  - Visuospatial learning: Ruff Light Trail Learning Test.
AB  - The assessment of memory typically includes tests for both audioverbal and
      visuospatial processing, while measurements of learning have primarily utilized
      the audioverbal mode. However, there exists no compelling reason why learning
      should not also be assessed in the visuospatial mode. The Ruff Light Trail
      Learning Test (RULIT) represents such an option. Normative values utilizing 307
      volunteers indicated neither significant gender nor educational differences.
      However, an age effect for those subjects 55 and older was demonstrated, and our
      data suggest that the major reason for the inferior learning in this older
      subgroup was their reduced memory capacities rather than their slowed
      visuospatial processing. Multiple components including learning curves, error
      analysis, and delayed recall are presented. Test-retest data also indicate an
      adequate reliability. The validity was compared to concurrently administered
      neuropsychological tests, and, finally, the potential for neuropsychological
      application of this new test is discussed.

PMID- 14588937
TI  - Benton Controlled Oral Word Association Test: reliability and updated norms.
AB  - The aim of this paper is to update the over 20-year-old normative data for the
      Benton Controlled Word Association (COWA) Test. In a sample of 360 normal
      volunteers, the age ranged between 16-70 years, and the educational level ranged
      from 7-22 years. Care was taken to ensure that the population was heterogeneous,
      yet the two stratifications of gender, four age, and three educational groups led
      to 24 cells with 15 individuals in each. Test-retest reliability was established
      by testing 30% of the sample after a 6-month delay, which represents a typical
      follow up duration between testings in a clinical setting. The two forms of the
      COWA revealed significant test-retest reliability. Generally, our updated values
      fall above the original normative values, which were derived from a less well
      educated and rural sample. No major gender or age trends were noted, but the COWA
      test performances were influenced by education, i.e., as the level of education
      increased, the performance on the COWA increased. The only gender differences
      that were found were for the women in the highest educational group ( > 16
      years), who performed significantly better that men in the highest educational
      group. An error analysis of repetitions or perseverations is provided, with cut
      off scores according to age levels. Finally, the updated COWA norms are compared
      to the original norms as well as to other measures of word fluency.

PMID- 14588938
TI  - The Digit Vigilance Test: reliability, validity, and sensitivity to diazepam.
AB  - The Digit Vigilance Test (DVT), a measure of sustained attention and psychomotor
      speed, was evaluated in terms of test-retest and alternate-form reliability as
      well as sensitivity to a single dose of diazepam (10 mg). A one-page version was
      compared to the standard two-page format. Forty undergraduates, randomly assigned
      in a double-blind manner to either drug or placebo condition, were tested three
      times in two sessions (1 week apart). Both Page 1 and Total Time scores were
      found to be highly reliable across time and forms. Repeated measures ANOVAs
      revealed the Total Time score, but not the Page 1 score, to be significant in
      discriminating diazepam from placebo across time, supporting the use of the
      complete DVT for measuring drug effects. Findings based on convergent measures
      also help to validate the DVT as a measure of sustained attention.

PMID- 14588939
TI  - Design fluency among normals and patients with closed head injury.
AB  - A Design Fluency task was administered to 86 patients who had suffered closed
      head injury (CHI) with loss of consciousness and 87 normal control subjects.
      Subjects were asked to draw as many novel designs as they could in 5 minutes
      without scribbling, drawing a nameable object, or repeating a design that had
      been drawn previously. The mean performance of the CHI group was significantly
      poorer than that of the control group, with 47% of head injured performing
      defectively (below the 5th percentile of controls There was no significant
      relationship between Design Fluency and prorated IQ, psychomotor speed, or Word
      Fluency. The findings demonstrate that a standardized version of the "free
      condition" of Design Fluency is likely to be useful in the evaluation of patients
      with closed head injury.

PMID- 14588942
TI  - The role of meta-analysis in medical decision making.

PMID- 14588943
TI  - Partitioning the contributing role of biomechanical, psychosocial, and individual
      risk factors in the development of spine loads.
AB  - BACKGROUND CONTEXT: The role of biomechanical workplace factors in spine loading
      has been well documented. However, our understanding of the role of psychosocial
      and individual factors in producing spine loads is poorly understood. Even less
      is understood about the relative contribution of these factors with respect to
      kinematic, kinetic and muscle activity responses, as well as spine loading.
      PURPOSE: To explore the relative contribution of biomechanical and psychosocial
      workplace factors and individual characteristics on the biomechanical responses
      and spine loading. STUDY DESIGN/SETTING: The contribution of various levels of
      workplace factors to spine loading was monitored under laboratory conditions.
      PATIENT SAMPLE: Sixty (30 male and 30 female) college-age individuals who were
      asymptomatic to low back pain. OUTCOME MEASURES: Trunk kinematics and kinetics,
      muscle activity and the three-dimensional spinal loads. METHODS: The subjects
      performed lifting tasks while being exposed to varying levels of biomechanical
      (lift rate, load weight and task asymmetry) and psychosocial (social support and
      mental concentration) workplace factors as well as an unexplored (load placement)
      workplace factor. RESULTS: The workplace job demands that had the largest
      contribution were load placement (4% to 30%) and load weight (15% to 55%). Mental
      concentration and social environment had a relatively small contribution to the
      spinal loads (up to 0.2%). Anthropometry played a large role in the shears (about
      12% to 58%) but a relatively minor role in the compressive forces (about 3%).
      CONCLUSIONS: Under the given experimental conditions, load weight is the most
      important factor when controlling compression forces associated with lifting, but
      other factors, such as individual characteristics, significantly contribute to
      the shear loads. Thus, one must account for the weight lifted and the
      anthropometric dimensions when designing the workplace. For the first time, the
      relative contribution of workplace job demands and individual factors in the
      development of spine loading have been identified.

PMID- 14588944
TI  - Power spectra of sternocleidomastoids, splenius capitis, and upper trapezius in
      oblique exertions.
AB  - BACKGROUND CONTEXT: There is relatively little known concerning the spectral
      profile of the cervical muscles, despite the fact that neck injury and pain are
      quite prevalent. PURPOSE: The objective of the study was to calculate and study
      the power spectral characteristics of the sternocleidomastoids, splenii capitis
      and upper trapezii in anterolateral flexion and posterolateral extension in a
      ramp contraction. STUDY DESIGN/SETTING: In a laboratory setting experiments were
      conducted to record surface electromyographic (EMG) data from six cervical
      muscles and power spectral variables obtained. PATIENT SAMPLE: Forty normal and
      healthy young adults (21 men, 19 women). OUTCOME MEASURES: Power spectral of EMG
      signals. METHODS: EMG data for the left and right isometric anterolateral flexion
      and posterolateral extension were acquired from the sternocleidomastoids, splenii
      capitis and upper trapezius bilaterally. The subjects were seated in an upright
      posture and exerted left and right anterolateral flexor and posterolateral
      extensor efforts from rest to their maximal voluntary contraction in a gradual
      linear ramp fashion using visual feedback as a guide. The force exerted and the
      surface EMG data were sampled at 1 kHz at every 10th percentile grade of
      contraction and the EMG data were subjected to the Fast-Fourier transform
      analysis. The median frequency (MF), mean power frequency (MPF), peak power and
      total power of all six cervical muscles were analyzed. RESULTS: In the
      anterolateral flexion the ipsilateral sternocleidomastoid and splenius capitis
      had a wider band of frequency, which further widened with increasing grade of
      contraction. The trapezius did not engage in the same manner or to the same
      magnitude. The MF of the sternocleidomastoid in the anterolateral flexion in both
      genders progressively increased, the splenius capitis remained relatively
      unchanged, and the upper trapezius declined with the increasing grades of
      contraction. CONCLUSIONS: There is no significant difference between the genders
      in spectral profile. There is a bilateral symmetry in spectral profile with
      reference to activity; however, they are significantly different in different
      activities for the same muscles. With increasing magnitude of contraction power,
      spectral density distribution increases and the median frequency decreases. These
      results can serve as a useful reference for painful necks. Restoration of power
      spectral characteristics may indicate normalcy, which cannot be gleaned by other
      EMG or force variables.

PMID- 14588945
TI  - Nerve monitoring changes related to iliac artery compression during anterior
      lumbar spine surgery.
AB  - BACKGROUND CONTEXT: There are no studies in the literature that correlate
      compression of the iliac vessels resulting in obstruction of blood flow with
      changes in nerve monitoring parameters during anterior lumbar surgery. PURPOSE:
      To determine whether there is significant compression of the iliac vessels that
      can cause temporary nerve root ischemia or limb ischemia that could be
      responsible for loss of somatosensory evoked potentials (SSEP) while retractors
      are in place for exposure during anterior lumbar interbody fusion (ALIF).
      SETTING: Patients coming to the operating room for ALIF from levels L2-L3 to L5
      S1 would be studied for nerve monitoring changes during the procedure with
      particular attention to the intervals just before placement of a retractor, while
      the retractor was in place and immediately after removal of the retractor.
      PATIENT SAMPLE: Forty-five consecutive patients were studied for changes in SSEP
      and oxygen saturation (SaO(2)) while undergoing ALIF. OUTCOME MEASURES: Patients
      were considered to have lost saturation if the SaO(2) decreased to below 90%.
      Patients were considered to have abnormal SSEP with any increase in latency and
      decrease in amplitude. METHODS: SSEP and SaO(2) were monitored continuously and
      simultaneously before exposure of the disc spaces, during exposure with
      retractors in place and after removal of the retractors. RESULTS: Thirteen of 23
      patients with exposure at L4-L5 had both loss of SSEP signals and loss of SaO(2)
      with exposure. All 13 patients had return to normal saturation and recovery of
      the SSEP signals within 15 minutes of removal of the retractors. Both of these
      are significant correlations (p<.001). CONCLUSION: This study showed that the
      majority (57%) of patients undergoing ALIF at the L4-L5 level are subject to
      compression of the left iliac vessels enough to cause desaturation distally as
      measured by pulse oxymetry. This vascular compromise, as well as the return to
      normal saturation, correlates with changes noted in SSEP soon after both
      deployment and removal of the retractors used for exposure. The mechanism appears
      to be a transient ischemic response. Failure of the SSEP signals to recover may
      be diagnostic of left iliac artery thrombosis.

PMID- 14588946
TI  - Surgeon perceptions of the complications and value of threaded fusion cages as a
      spine fusion technique: results of a consensus survey.
AB  - BACKGROUND CONTEXT: Threaded cage technology has had a meteoric rise in usage. It
      has been touted as a procedure with low risk and minimal complications. PURPOSE:
      To gauge the spine surgical community's general consensus regarding cage usage
      and its complications. STUDY DESIGN/SETTING: A canvassing questionnaire regarding
      threaded cage usage and complications was sent to members of the North American
      Spine Society. PATIENT SAMPLE: A total of 665 doctors reported on their
      perception of 22,585 cages placed by the second year after pre-market approval
      from the Food and Drug Administration approval. OUTCOME MEASURES: A nonscientific
      canvassing questionnaire was thought to give a consensus of surgical outcome
      perception in a large number of caregivers with hopes of understanding general
      trends. METHODS: Simple statistical measurements were used to report perceived
      complications by surgeons involved in performing threaded cage surgical
      procedures. RESULTS: Sixty-nine percent of doctors reported at least one
      complication with threaded cages, but the complication incidence was low.
      Visceral injuries were reported in 0.1%; vascular injuries, 1.0%; cage
      displacement and dislodgement, 1.4%; temporary and permanent neurologic injuries,
      2.25% and 0.56%, respectively; infection 0.34%; retrograde ejaculation 1.2% and
      revision surgery recorded for 2.7%. Those rating cages as fair to poor (16.5%)
      were those physicians reporting the longest experience with this technology.
      CONCLUSIONS: The general consensus is that threaded cages have low complication
      rates and high satisfaction rates, 83.5%. The data represent a convenience
      sampling and is not scientific.

PMID- 14588947
TI  - Pulsed radiofrequency application in treatment of chronic zygapophyseal joint
      pain.
AB  - BACKGROUND CONTEXT: Chronic zygapophyseal joint arthropathy is a cause of back
      and neck pain. One proposed method of treating facet joint pathology is ablation
      of medial branches and dorsal rami with pulsed radiofrequency (RF) waves.
      PURPOSE: Assessment of efficacy of pulsed RF application for treatment of chronic
      zygapophyseal joint pain. STUDY DESIGN/SETTING: Retrospective study of 114
      patients at a pain management clinic. PATIENT SAMPLE: A total of 114 patients
      with clinical signs of facet joint involvement and a favorable response to a
      diagnostic medial branch block using local anesthetic, including 82 females and
      32 males with a mean age of 52.8+/-12.6 years. Mean duration of pain was 7.52+/
      5.26 years. Twenty-seven had previous back surgery, 83 patients had low back pain
      and 31 had cervical pain. Pain was on the left side in 47 patients, on the right
      side in 45 patients, bilateral in 22. OUTCOME MEASURES: Result was regarded as
      successful if pain reduction was more than 50% on visual analog scale and the
      duration of effect was more than 1.5 months. METHODS: After obtaining positive
      stimulation, pulsed RF was applied to medial branches of dorsal rami for 120
      seconds with temperature at the tip of the electrode 42 C. RESULTS: Of 114
      patients, who had positive response to diagnostic block, 46 patients did not
      respond favorably to pulsed RF application (pain reduction less than 50%). In 68
      patients, the procedure was successful and lasted on average 3.93+/-1.86 months.
      Eighteen patients had the procedure repeated with the same duration of pain
      relief that was achieved initially. Previous surgery, duration of pain, sex,
      levels (cervical vs. lumbar) and stimulation levels did not influence outcomes.
      CONCLUSION: The results of our study showed that the application of pulsed RF to
      medial branches of the dorsal rami in patients with chronic facet joint
      arthropathy provided temporary pain relief in 68 of 118 patients.

PMID- 14588948
TI  - Effect of torso flexion on the lumbar torso extensor muscle sagittal plane moment
      arms.
AB  - BACKGROUND CONTEXT: Accurate anatomical inputs for biomechanical models are
      necessary for valid estimates of internal loading. The magnitude of the moment
      arm of the lumbar erector muscle group is known to vary as a function of such
      variables as gender. Anatomical evidence indicates that the moment arms decrease
      during torso flexion. However, moment arm estimates in biomechanical models that
      account for individual variability have been derived from imaging studies from
      supine postures. PURPOSE: Quantify the sagittal plane moment arms of the lumbar
      erector muscle group as a function of torso flexion, and identify individual
      characteristics that are associated with the magnitude of the moment arms as a
      function of torso flexion. STUDY DESIGN/SETTING: Utilization of a 0.3 Tesla Open
      magnetic resonance image (MRI) to image and quantify the moment arm of the right
      erector muscle group as a function of gender and torso flexion. METHODS: Axial
      MRI images through and parallel to each of the lumbar intervertebral discs at
      four torso flexion angles were obtained from 12 male and 12 female subjects in a
      lateral recumbent posture. Multivariate analysis of variance was used to
      investigate the differences in the moment arms at different torso flexion angles,
      whereas hierarchical linear regression was used to investigate associations with
      individual anthropometric characteristics and spinal posture. RESULTS: The
      largest decrease in the lumbar erector muscle group moment arm from neutral to 45
      degree flexion occurred at the L5-S1 level (9.7% and 8.9% for men and women,
      respectively). Measures of spinal curvature (L1-S1 lordosis), body mass and trunk
      characteristics (depth or circumference) were associated with the varying moment
      arm at most lumbar levels. CONCLUSIONS: The sagittal plane moment arms of the
      lumbar erector muscle mass decrease as the torso flexes forward. The change in
      moment arms as a function of torso flexion may have an impact on prediction of
      spinal loading in biomechanical models.

PMID- 14588949
TI  - Somatosensory evoked potential monitoring of lumbar pedicle screw placement for
      in situ posterior spinal fusion.
AB  - BACKGROUND CONTEXT: Somatosensory evoked potentials (SSEP) are commonly used to
      monitor the spinal cord and nerve roots during operative procedures that put
      those structures at risk. The utility of SSEPs to evaluate cauda equina and nerve
      root function during posterior spinal arthrodesis with pedicular fixation for
      degenerative lumbar disease has been reported anecdotally and remains
      controversial. PURPOSE: An institution-wide review of the ability of SSEP
      readings to monitor nerve function during posterior lumbar spinal arthrodeses
      with transpedicular fixation for degenerative lumbar spinal disorders was
      undertaken. STUDY DESIGN/SETTING: A retrospective review was undertaken. Patient
      history, preoperative physical examination, intraoperative anesthesia, SSEP
      records and the postoperative course were reviewed. METHODS: A total of 186
      consecutive arthrodeses as described above were reviewed. Patients who had
      anterior procedures, spondyloreduction or scoliosis correction were excluded from
      the study. There were 76 male and 110 female patients. Five fellowship-trained
      spine surgeons placed a total of 888 pedicle screws. Sixty-five percent of the
      patients had a principal preoperative diagnosis of spinal stenosis with
      degenerative spondylolisthesis. Other common diagnoses were isthmic
      spondylolisthesis and degenerative scoliosis. Ninety-three percent of the cases
      involved decompressive laminectomy. Eight percent had posterior interbody
      fusions. All pedicle screws were placed without the assistance of fluoroscopy or
      stereotactic computer-assisted guidance. Screw position was evaluated
      intraoperatively with standard posteroanterior and lateral radiographs.
      Anesthetic agents compatible with SSEP monitoring were used in all patients. SSEP
      baseline readings were obtained in all patients in the operating room soon after
      induction of general anesthesia. An acute and sustained loss of 50% of the SSEP
      amplitude and/or increase by 10% of latency from baseline was considered to be
      pathologic. RESULTS: None of the 186 patients had significant SSEP changes. There
      were, however, 5 patients with postoperative radiculopathies distinct from their
      preoperative presentations. Early postoperative plain radiographs and computed
      assisted tomography (CAT) scans revealed malpositioned pedicle screws.
      Consequently, eight pedicle screws were either revised or removed. All patients
      had partial or full recovery of their new deficits after revision surgery.
      CONCLUSION: We conclude that the use of SSEPs in evaluating pedicle screw
      placement during lumbar arthrodesis is limited. In this setting, if monitoring is
      required, alternative methods with greater sensitivity and efficacy should be
      explored.

PMID- 14588950
TI  - Bilateral implantation of low-profile interbody fusion cages: subsidence,
      lordosis, and fusion analysis.
AB  - BACKGROUND CONTEXT: The use of interbody fusion cages as a treatment for
      degenerative disc disease has become widespread. Low-profile cages have been
      developed to allow a closer fit when implanting bilateral cages in patients with
      smaller vertebral bodies. Some surgeons feel the open design also allows better
      bone contact and visualization. This is particularly true when two low-profile
      cages are used adjacent to one another. Because of the open design of low-profile
      interbody fusion cages, there has been concern regarding such issues as
      subsidence, lordosis and fusion rates. PURPOSE: This retrospective review of
      paired bilateral reduced profile interbody fusion cages was completed to assess
      changes in subsidence, lordosis and fusion. As a secondary goal, patient outcomes
      were measured to determine overall health since surgery and the patient's
      satisfaction with the spine surgery, in an attempt to assess the effect of the
      outcome variables cited supra. STUDY DESIGN: This was a retrospective evaluation
      of patients who underwent anterior lumbar interbody fusion with low-profile
      interbody fusion cages. PATIENT SAMPLE: Seventy-one consecutive patients who
      underwent bilateral implantation of low-profile interbody fusion cages were
      evaluated. OUTCOME MEASURES: A patient self-evaluation, which included a Short
      Form (SF)-36 and questions regarding patient satisfaction were administered to
      patients who were at least 1 year postoperative. Subsidence and lordosis
      measurements were completed. Fusion was assessed by the operating surgeon.
      METHODS: Low-profile interbody fusion cages (BAK/Proximity, Centerpulse Spine
      Tech, Inc., Minneapolis, MN) were implanted bilaterally in at least one level
      from L3-L4 to L5-S1. Most patients had degenerative disc disease with leg and
      back pain that was not responsive to conservative treatment and demonstrated
      segmental instability or collapse. A small percentage of patients had either a
      degenerative spondylolisthesis (7.0%) or an isthmic spondylolisthesis (4.2%).
      Autograft harvested from the iliac crest was used in all cases. Demographic,
      surgical and follow-up data were retrospectively collected from patient charts. A
      clinical outcome questionnaire that included an SF-36 as well as questions
      regarding patient satisfaction was either mailed to each patient who was at least
      1 year postsurgery or given to patients to complete at their 1-year visit.
      Patients were routinely followed radiographically before surgery, immediately
      after surgery and at 3, 6, 12 and 24 months after surgery. Fusion was assessed by
      the operating surgeon using lateral radiographs often in conjunction with a thin
      slice computed tomography (CT) scan. Criteria for a successful fusion were lack
      of motion, anterior bridging bone and lack of lucencies on flexion/extension X
      rays and/or contiguous bone through the cage using a thin-cut sagittal CT scan.
      Lateral X-rays on each patient were also measured for subsidence and lordosis
      changes. RESULTS: A total of 71 patients (45 men, 26 women) with a mean age of
      43.4 years (range, 25 to 74) were evaluated. Thirty-six percent of the patients
      were smokers, and 96% were worker's compensation patients. Thirty-two percent of
      the patients had previous lumbar surgery. A total of 100 operative levels were
      evaluated. There were 45 one-level, 23 two-level and three three-level cases.
      Forty-nine percent were level L5-S1, 43% were L4-L5 and 8% were L3-L4. The mean
      duration of symptoms was 31.5 months. Mean surgical time, mean blood loss and
      mean hospital stay were 139 minutes, 186 cc and 3.34 days, respectively. There
      were no intraoperative or postoperative complications attributable to the
      construct and no cases of cage migration or collapse. Patients who were at least
      1-year postsurgery and had follow-up X-rays or had undergone a CT scan at this
      time point were evaluated for fusion status. Sixty-three patients were assessed
      for fusion. Fifty-four (86%) of these patients were determined to have a solid
      fusion. Mean time to fusion was 10 months. Fusion was assessed as solid only if
      all operative levels were fully fused. Mean subsidence of the anterior region was
      1.97 mm, whereas the mean subsidence of the posterior region was 0.82 mm.
      Lordosis was unchanged at all surgical levels with mean lordosis in L3-L4
      decreasing only slightly from 13 degrees before surgery to 12 degrees after
      surgery. L4-L5 and L5-S1 showed only slight increases in lordosis changing from
      17 to 18 degrees at L4-L5 and from 17 to 19 degrees at L5-S1. These changes were
      not statistically significant. The clinical outcome questionnaires had a return
      rate of 68%. Of the 48 patients who completed the questionnaire, 75% responded
      that they were happy with the surgical results and would definitely recommend the
      surgery to a friend. Sixty-seven percent agreed that surgery met their
      expectations or that surgery improved their condition enough that they would go
      through it again for the same outcome. The results of the SF-36 portion of the
      survey revealed that the physical and mental composite scores were within normal
      range of the US population that has experienced back pain or sciatica.
      CONCLUSION: Bilateral implantation of low-profile cages in this patient
      population led to satisfactory outcomes. Subsidence and changes in lordosis were
      minimal. Fusion rates were good, especially for one-level cases. Patient
      satisfaction was relatively high, considering the population consisted of 96%
      worker's compensation cases. With proper surgical technique, bilateral low
      profile cages can be used effectively to treat patients with degenerative disc
      disease.

PMID- 14588951
TI  - Perioperative blood and blood product management for spinal deformity surgery.
AB  - BACKGROUND CONTEXT: Spinal deformity surgery, like many other orthopedic
      procedures, involves significant operative blood loss. In order to avoid the
      necessity of bank blood transfusions, many blood management strategies have been
      devised. PURPOSE: The goal of this review is to analyze the utility of current
      blood management strategies. STUDY DESIGN/SETTING: Review paper. METHODS: Using
      Medline reviews, pertinent data on blood management agents and strategies were
      assembled. RESULTS: Techniques can be organized into preoperative, intraoperative
      and postoperative categories. Preoperative techniques include autologous blood
      donation and red cell augmentation. In addition to some established surgical and
      anesthesia techniques, recent pharmacologic agents have become available to
      include thrombotic agents and antifibrinolytics, which surgeons may add to their
      intraoperative armamentarium. A brief mention of postoperative blood salvage
      drains is also included. CONCLUSIONS: The judicious use of the agents and
      techniques can significantly reduce the need for blood transfusions in the
      setting of spinal deformity surgery.

PMID- 14588952
TI  - Delayed infection after instrumented spine surgery: case reports and review of
      the literature.
AB  - BACKGROUND CONTEXT: A delayed infection after instrumented spine surgery can be
      difficult to diagnose because of its low incidence and variety of clinical
      symptoms. PURPOSE: To describe four cases of delayed infection after instrumented
      spine surgery and to review the literature of such cases with regard to the
      clinical symptoms and risk factors, possible causes of infection and treatment.
      STUDY DESIGN/SETTING: Personal review of cases and literature review. PATIENT
      SAMPLE: Four cases in this report and 93 other cases reported in the literature.
      OUTCOME MEASURES: Not measured. METHODS: Summary of the clinical symptoms, risk
      factors, causes of infection and treatment regimens. RESULTS: Three possible
      causes of a delayed infection have been cited: intraoperative seeding, metal
      fretting causing a sterile inflammatory response or stimulating low-virulent
      organisms to fester and hematogenous seeding. A variety of clinical symptoms were
      found, but spontaneous drainage appears to be most common. Many patients had
      either a fluctuant mass, localized drainage or an abscess. Abscesses or drainage
      material is typically contiguous with the instrumentation and the fusion mass.
      Fever was present in only six patients. Effective treatment usually includes
      removal of the implants, irrigation and debridement, followed by the
      administration of antibiotics. CONCLUSIONS: A high level of suspicion is needed
      to diagnose a delayed infection after instrumented spine surgery.

PMID- 14588953
TI  - Failed back surgery: etiology and diagnostic evaluation.
AB  - BACKGROUND CONTEXT: This is a synopsis of a symposium presented to the North
      American Spine Society Annual Meeting in Montreal, Canada, 2002. PURPOSE: To
      provide the reader with a distillation of the material presented regarding the
      diagnosis of failed back surgery syndrome (FBSS). METHODS: Panel presentation.
      RESULTS: The proper treatment of patients with FBSS depends on a precise and
      accurate diagnosis. With a careful history, examination, imaging studies,
      psychological evaluation and diagnostic injections, a diagnosis can be reached in
      over 90% of patients. The most common diagnoses are foraminal stenosis (25% to
      29%), painful disc (20% to 22%), pseudarthrosis (14%), neuropathic pain (10%),
      recurrent disc herniation (7% to 12%), facet joint pain (3%) and sacroiliac joint
      (SIJ) pain (2%). Psychological factors are always present and may help or hinder.
      Common psychological diagnoses include depression, anxiety disorder and substance
      abuse disorder. Diagnostic injections are very useful for facet joint pain, SIJ
      pain and discogenic pain; they may also be used to confirm a putative neural
      compression as a cause of pain. CONCLUSIONS: Spine surgeons must be aware of the
      common causes of FBSS in order to be able to thoroughly evaluate their patients
      and to minimize the occurrence of this problem.

PMID- 14589182
TI  - Prolotherapy at the fringe of medical care, or is it the frontier?

PMID- 14589183
TI  - Lumbar spine listhesis in older African American women.
AB  - BACKGROUND CONTEXT: Degenerative changes in the lumbar spine may result in a loss
      of spinal stability and subluxation of one vertebra relative to another.
      Cadaveric studies and clinical case series have suggested that listhesis may be
      much more common in African Americans than in whites. PURPOSE: To determine the
      prevalence of lumbar spine listhesis (anterolisthesis and retrolisthesis) among
      African American women aged 65 years and older and the relationship of listhesis
      to low back pain, physical function and quality of life. STUDY DESIGN/SETTING:
      Cross-sectional study. PATIENT SAMPLE: A total of 481 African American women aged
      65 years and older who were enrolled in the Study of Osteoporotic Fractures.
      These women were recruited from population-based listings in Baltimore, MD,
      Minneapolis, MN, Pittsburgh, PA, and Portland, OR. OUTCOME MEASURES: Not
      applicable. METHODS: Lateral radiographs of the lumbar spine were digitized, and
      listhesis (anterolisthesis and retrolisthesis) was assessed at spinal levels L3
      L4, L4-L5 and L5-S1. Usable data were obtained for 470 women. Listhesis was
      defined as present when the subluxation (antero or retro) was 3 mm or more.
      RESULTS: The overall prevalence of anterolisthesis was 58.3% and varied by spinal
      level (13.2% at L3-L4, 36.5% at L4-L5 and 29.6% at L5-S1). The prevalence
      increased with age but was lower among oophorectomized women and those currently
      on estrogen replacement therapy. Anterolisthesis was not associated (p>.05) with
      disc height nor was it related to back function. Retrolisthesis occurred in 4% of
      women and was associated with decreased disc height and an increased prevalence
      of spinal problems and walking problems. CONCLUSIONS: The prevalence of
      anterolisthesis among older African American women living in the community was
      two to three times greater than that found in white women of a similar age. This
      condition was not related to an increased frequency of back problems nor did it
      adversely affect general physical function. Retrolisthesis was relatively rare
      but was associated with decreased back function.

PMID- 14589184
TI  - Biomechanical comparison of cervical interbody cage versus structural bone graft.
AB  - BACKGROUND CONTEXT: Clinically, cervical interbody cages provide fusion rates
      equivalent to structural bone grafting. No published studies have biomechanically
      compared cages with grafts. PURPOSE: We sought to compare the stability offered
      by threaded interbody cages versus structural bone graft and to evaluate the
      additional stability provided by adding a one- or two-level anterior plate to
      both interbody techniques. STUDY DESIGN/SETTING: Nondestructive nonconstraining
      repeated-measures in vitro flexibility tests were performed on surgically
      instrumented specimens. SUBJECT SAMPLE: Sixteen human cadaveric specimens were
      separated into two groups (specimens receiving graft and specimens receiving
      cage) with matched bone mineral density. OUTCOME MEASURES: Angular range of
      motion (ROM), neutral zone (NZ) and elastic zone (EZ) were quantified to assess
      stability. Student's t tests compared outcomes between and within groups.
      METHODS: Quasistatic nonconstraining torques (maximum 1.5 Nm) induced flexion,
      extension, lateral bending and axial rotation while angular motion was recorded
      stereophotogrammetrically. Specimens were tested normal, after discectomy, with
      graft or cage, with two-level plate and with one-level plate. RESULTS: Graft
      alone and cage alone reduced ROM and EZ but not NZ to within normal. In both
      groups, adding a one- or two-level plate significantly reduced motion in all
      modes of loading. There were no significant differences in motion parameters
      between groups whether plated or unplated. A two-level plate provided
      significantly better stability than a one-level plate. CONCLUSIONS: The interbody
      cage performed equivalently to the structural graft. Substantial increases in
      stability can be gained for either interbody technique by adding an anterior
      plate.

PMID- 14589185
TI  - Multidisciplinary rehabilitation versus usual care for chronic low back pain in
      the community: effects on quality of life.
AB  - BACKGROUND CONTEXT: Multidisciplinary biopsychosocial rehabilitation has been
      shown in controlled studies to improve pain and function in patients with chronic
      back pain. However, specialized back pain rehabilitation centers are rare and
      only a few patients can participate on this therapy. Implementation of
      multidisciplinary rehabilitation services in community medicine may enhance both
      early availability and treatment capacity for comprehensive back pain
      rehabilitation. PURPOSE: To compare the outcome of a multidisciplinary
      rehabilitation program (MRP) that was organized by cooperation of local health
      care providers in the community with that of the usual care by independent
      physicians for patients with chronic low back pain. STUDY DESIGN: A comparison
      between the outcomes (follow-up time of 6 months) of treatment for chronic back
      pain in the community in a prospective intervention group versus a prospective
      observational usual care group. PATIENT SAMPLE: All patients were recruited from
      independent physicians in the community of a selected region who participated
      voluntarily in the study. Patients were included in the study if they were
      seeking treatment of pain in the back with possible irradiation into the legs,
      the pain persisted for at least 3 months without decreasing intensity and there
      was no indication for surgical intervention. OUTCOME MEASURES: Outcome was
      assessed from patients' responses in self-report questionnaires at baseline and
      after an interval of 6 months. For outcome, we evaluated the health-related
      quality of life (German version of Short Form [SF] 36), the average pain severity
      (Numeric Rating Scale), the pain-related interference of function (German version
      of Brief Pain Inventory), depression (Allgemeine Depressionsskele), time off from
      work within 3 months before entering and leaving the study and the self-appraisal
      of improvement. METHODS: In a baseline group, the independent physicians treated
      the patients with usual care. In the intervention group, the patients were
      referred by the independent physicians to the study coordinator in the outpatient
      facilities of the Departments of Neurology or Orthopedics for inclusion in the
      MRP. The MRP was organized by cooperation of local health-care providers in the
      community with different specialties (sport teachers, clinical psychologist,
      physiotherapist and physician) who were experienced in the management of back
      pain. The MRP (4 hours per day, 3 days per week, 20 days) included 1.5 hours
      restorative exercise therapy, 0.5 hours physiotherapy, 1 hour cognitive
      behavioral therapy, 0.5 hours progressive muscle relaxation and 0.5 hours
      education. RESULTS: Complete data sets were obtained from 157 patients in the
      usual care group (documented by 35 independent physicians) and 51 patients in the
      MRP group. Patients of the MRP group improved in the physical and mental health
      domains of the SF-36 more than patients treated by usual care (p<.05).
      Furthermore, days off work were more (p<.05) reduced by the MRP (16+/-35 days)
      than by usual care (-2+/-39 days). Finally, overall appraisal of successful
      outcome was better (p<.01) after MRP (54% of patients) as compared with usual
      care (24% of patients). However, the pain intensity (NRS), the pain-related
      interference with function (Brief Pain Inventory; BPI) and the depression scores
      (ADS) did not differ significantly between both groups. CONCLUSIONS: MRP is
      promising to improve health-related quality of life for patients with chronic
      back pain in the community. Before implementation of MRP in the repertoire of
      community medicine, superiority of MRP over usual care should be confirmed by a
      randomized controlled trial.

PMID- 14589186
TI  - Reduction of epidural fibrosis in lumbar surgery with Oxiplex adhesion barriers
      of carboxymethylcellulose and polyethylene oxide.
AB  - BACKGROUND CONTEXT: Postsurgical epidural adhesions and fibrosis after surgery
      for lumbar disc herniation are a consequence of normal wound healing. The
      presence of fibrosis renders reoperations risky, and in some patients fibrosis
      may lead to nerve root tethering. PURPOSE: One approach to minimizing the risk of
      developing epidural adhesions is to provide a barrier between the dural membrane
      and the healing connective tissues. The purpose of these studies was to evaluate
      such a barrier device. STUDY DESIGN/SETTING: In vivo investigation in an animal
      model at a university laboratory. PATIENT SAMPLE: Rabbit. OUTCOME MEASURES: Gross
      and histomorphic evaluation. METHODS: Barriers comprised of
      carboxymethylcellulose (CMC) and polyethylene oxide (PEO) (Oxiplex; FzioMed,
      Inc., San Luis Obispo, CA) were studied as devices to reduce epidural adhesion
      formation in rabbit laminotomy and laminectomy models. The barriers tested were
      either a gel alone (gel) or a gel covered with a film (gel/film combination). Two
      laminotomy or laminectomy sites (depending on the surgical method) were created
      in each rabbit at L4 and L6. One site was treated with a CMC/PEO gel, or CMC/PEO
      gel/film combination, and the other site served as a surgical control. Two
      surgical models that differed in the extent of adhesion formation at untreated
      injury sites and the method of injury generation were used. RESULTS: Model A,
      which did not incorporate dural abrasion, resulted in up to 40% adhesion-free
      laminectomy sites in controls. Model B, which did incorporate abrasion of the
      dural membrane, resulted in less than 10% adhesion-free laminotomy sites in
      controls. Compositions of CMC/PEO gels (2.5% to 10% PEO) and films (22.5% PEO)
      were tested in both models. Efficacy parameters included measuring the number of
      sites free of epidural fibrosis and reduction in the severity of fibrosis
      (adhesions). Both gels and gel/film combinations consistently reduced the
      frequency and the extent of epidural fibrosis in both models. Gels of CMC/PEO
      containing a higher content of PEO (10%) and a higher molecular weight of PEO
      (4.4 mD) were most effective in Model B and resulted in up to 84% laminotomy
      sites with minimal or no epidural fibrosis, whereas controls exhibited over 90%
      of the sites with epidural fibrosis. Histological evaluation of the surgical
      sites indicated that the reduction of epidural fibrosis was accompanied by normal
      bone healing. In addition, these experiments demonstrated that the gel/film
      combination provided no additional benefit to that obtained by the gel alone.
      CONCLUSIONS: Gels of CMC/PEO reduced epidural fibrosis and did not impair normal
      heal ing.

PMID- 14589188
TI  - In vitro osteoblast proliferation as a predictor for spinal fusion mass.
AB  - BACKGROUND CONTEXT: The biological factors determining a successful spinal fusion
      have not yet been fully determined. PURPOSE: To determine the influence of graft
      cell vigor on fusion rate and fusion mass using in vitro osteoblast proliferation
      as a predictor. STUDY DESIGN: Animal study randomizing to posterolateral fusion
      with autograft with or without pedicle-screw instrumentation. PATIENT SAMPLE:
      Twenty adult Gottingen mini-pigs. OUTCOME MEASURES: Fusion rate measured both
      with X-ray and computed tomography (CT) as well as amount of fusion mass
      determined with three-dimensional CT. METHODS: Animals underwent posterolateral
      fusion with autograft either with or without pedicle-screw instrumentation.
      Additional graft was harvested for osteoblastlike cell culture. Cells were
      counted after 3 weeks, and their proliferative capacity was correlated to fusion
      rate and fusion amount. RESULTS: Cell count was significantly higher in the fused
      animals (p<.011). Furthermore, a tendency toward a positive correlation to fusion
      mass amount was observed (p<.091). CONCLUSIONS: The achievement of a solid spinal
      fusion using autograft is related to properties of the bone-forming cells in the
      graft and fusion bed. Most likely it is the number of cells and not their
      proliferative capacity that is the most important factor.

PMID- 14589189
TI  - Anterior lumbar fusion with paired BAK standard and paired BAK Proximity cages:
      subsidence incidence, subsidence factors, and clinical outcome.
AB  - BACKGROUND CONTEXT: Anterior lumbar interbody fusion (ALIF) procedures have a
      known incidence of subsidence. The individual risk of subsidence for specific
      lumbar levels in ALIF procedures has not been determined. PURPOSE: To evaluate
      the incidence of subsidence with two ALIF constructs. A paired Bagby and Kuslich
      (BAK) standard cage construct is compared with a paired BAK Proximity construct
      (Sulzer Spine-Tech, Minneapolis, MN). Study purpose is to evaluate lumbar
      intervertebral disc subsidence including the subsidence incidence for each disc
      level and with single- and two-level constructs. Also evaluated is the site of
      maximal subsidence within each end plate, risk with increased reaming depth,
      fusion incidence and clinical outcome. STUDY DESIGN: A consecutive series of 70
      fused levels fused with paired standard BAK cages is compared with a subsequent
      series of 70 fused levels using paired Proximity BAK cages. PATIENT SAMPLE: The
      study population is derived from a consecutive series of ALIF procedures
      completed by a single surgeon. In 1998 the construct was changed from dual
      standard to dual-Proximity cages. In the year 2000 there were 52 patients with a
      2-year follow-up. These were matched to the previous 52 patients with dual
      standard construct. OUTCOME MEASURES: Clinical outcome was determined using pre-
      and postoperative Oswestry questionnaires. Postoperative questionnaires were
      completed at the yearly follow-up. Radiographic outcome was determined by fusion
      status and evaluation of subsidence. Also evaluated was reaming depth and cage
      size for each fused level. METHODS: A total of 52 patients with ALIF procedures
      using paired BAK standard cages (the SS group) were studied with a group of 52
      patients using paired BAK Proximity cages (the PP group). The study population
      was derived from an ongoing prospective study of consecutive ALIF fusion
      procedures completed by a single surgeon. Disc height measurements were used to
      determine subsidence. Reaming depth, fusion status and the site of maximal
      subsidence were all recorded. Clinical outcome was determined with a pre- and
      postoperative Oswestry functional questionnaire. RESULTS: Subsidence greater than
      2 mm was noted in 5 of the 70 SS fused levels and in 9 of the 70 fused PP levels.
      Subsidence was always at the L4-L5 level in the SS subsided levels. Subsidence
      was in two-level fusions in all but one of the SS constructs. Subsidence was at
      the L4-L5 level in eight of the nine subsided PP levels. Subsidence was
      associated with increased reaming depth and the use of larger cage sizes.
      Subsidence was usually in the posterior and superior end plate. The clinical
      outcome was not affected by subsidence. Subsidence incidence was not associated
      with the age, sex or weight of the patient. CONCLUSIONS: There is a statistically
      significant increased incidence of subsidence at the L4-L5 level as opposed to
      other fused lumbar levels in ALIF fusions with BAK cage constructs. There is an
      increased incidence of subsidence with the PP constructs. Subsidence also is
      associated with increased reaming depth and with larger cage sizes. The lowest
      risk for subsidence was with single-level dual-standard cage constructs.

PMID- 14589190
TI  - Single stage anterior cervical reconstruction with titanium mesh cages, local
      bone graft, and anterior plating.
AB  - BACKGROUND CONTEXT: After cervical corpectomy, the use of tricortical autologous
      bone to fill the large defect is biomechanically and structurally inadequate and
      may lead to excessive donor site pain and morbidity. The major alternative,
      fibular strut allograft, has inherent problems that lead to lower rates of solid
      arthrodesis and graft migration. Majd et al. reported on 34 cases with a 97%
      solid fusion rate using titanium mesh cages and local bone graft to fill the
      cervical corpectomy defect. PURPOSE: With long-term results, to confirm the
      results previously reported by Majd et al. STUDY DESIGN/SETTING: Retrospective
      chart and radiological review. PATIENT SAMPLE: The first 26 patients in the
      senior author's practice eligible for a minimum 2-year follow-up, having had
      cervical corpectomy reconstructed with titanium mesh cages, local bone graft and
      anterior plating. OUTCOME MEASURES: Odom's criteria were used to assess clinical
      outcome. Anteroposterior, lateral and lateral flexion and extension radiographs
      were used to assess fusion. METHODS: Twenty-six patients with multilevel cervical
      pathology underwent successful corpectomy, decompression and fusion with titanium
      mesh cages filled with local bone graft. Rigid anterior plating was applied
      across the corpectomy defect. Preoperative, operative and postoperative chart
      data were collected retrospectively. Radiographic assessment included a minimum 2
      year follow-up. RESULTS: Follow-up ranged from 24 to 64 months. Clinically, 21 of
      26 (80.7%) had an excellent or good clinical outcome. No radiolucencies or motion
      were detected on radiographic analysis, yielding a fusion rate of 100% (26 of
      26). Broken or pulled out screws were identified in two patients, one of whom had
      plate revision. All cages remained intact with no evidence of cage settling or
      collapse. CONCLUSIONS: The use of titanium mesh cages in conjunction with local
      bone graft, and rigid anterior plating is effective for cervical reconstruction
      after corpectomy and a viable alternative to the use of fibular strut allograft.
      These results confirm those previously reported by Majd et al.

PMID- 14589191
TI  - Intervertebral cages for degenerative spinal diseases.
AB  - Interbody fusion techniques have been used for many years for the treatment of a
      variety of lumbar spine diagnoses. Part of the interest in increasing methods of
      interbody fusion has stemmed from concern that posterior fusion alone may allow
      micro-motion, which may generate pain in a ruptured or degenerated disc.
      Stabilization of the anterior segment led to the development of interbody fusion
      cages. These devices were designed to stabilize the spine while bony ingrowth
      from the vertebrae to the bone graft occurred. There are a variety of techniques
      for cage insertion, including open and laparoscopic techniques anteriorly, and
      open posterior approach. A lateral approach for cage placement has also been
      reported. The purpose of this paper is to present a review of the literature on
      lumbar intervertebral fusion performed using interbody cages. The reported
      results for these procedures vary, but in general the majority of patients have
      had favorable results. The complications are similar to those encountered with
      traditional interbody fusion procedures using bone grafts. There is a learning
      curve associated with the procedures, particularly with the laparoscopic
      techniques. Appropriate training for the spine surgeon as well as the access
      surgeon is important. There is a great deal of disparity in reports on using the
      cages as stand-alone devices as well as on laparoscopic approaches. Overall, the
      use of interbody cages for fusion appears to be a viable treatment, yielding good
      results. Fusion cages appear to have a role in spine care; however, as with any
      procedure, patient selection and proper training of the surgeon are critical.

PMID- 14589192
TI  - A critical review of the evidence for the use of zygapophysial injections and
      radiofrequency denervation in the treatment of low back pain.
AB  - BACKGROUND CONTEXT: Lumbar zygapophysial joints are currently believed to be a
      cause of axial low back pain. Once this diagnosis is made, decisions about when
      to institute a particular intervention and which treatment to offer is regionally
      and specialty dependent. PURPOSE: To perform a critical review of prior published
      studies assessing the use of interventional treatment options for the treatment
      of lumbar zygapophysial joint syndrome. STUDY DESIGN: Evidence-based medicine
      analysis of current literature. METHODS: A database search of Medline (PubMed,
      Ovid and MDConsult), Embase and the Cochrane database was conducted. The keywords
      used were low back pain, lumbar zygapophysial joint, lumbar facet joint,
      radiofrequency denervation, medial branch block, and intraarticular injection.
      After identifying all relevant literature, each article was reviewed. Data from
      the following categories were compiled: inclusion criteria, randomization of
      subjects, total number of subjects involved at enrollment and at final analysis.
      statistical analysis used, intervention performed, outcome measures, follow-up
      intervals and results. Guidelines described by the Agency for Health Care Policy
      and Research were then applied to these data. RESULTS: This review determined
      that the evidence for the treatment of lumbar zygapophysial joint syndrome with
      intraarticular injections should be rated as level III (moderate) to IV (limited)
      evidence, whereas that for radiofrequency denervation is at a level III.
      CONCLUSIONS: Current studies fail to give more than sparse evidence to support
      the use of interventional techniques in the treatment of lumbar zygapophysial
      joint-mediated low back pain. This review emphasizes the need for larger,
      prospective, randomized controlled trials with uniform inclusion and exclusion
      criteria, standardized treatment, uniform outcome measures and an adequate
      duration of follow-up period so that definitive recommendations for the treatment
      of lumbar zygapophysial joint-mediated pain can be made.

PMID- 14589193
TI  - Abdominal pain secondary to a sacral perineural cyst.
AB  - BACKGROUND CONTEXT: Perineural cysts are commonly found in the sacral region and
      are incidently discovered on imaging studies performed for the evaluation of low
      back and/or leg pain. PURPOSE: To report on a patient presenting with abdominal
      pain secondary to a large sacral perineural cyst. STUDY DESIGN/SETTING: Case
      report. METHODS/PATIENT SAMPLE: A 47-year-old woman was referred to a specialized
      multidisciplinary spine center with complaints of left lower quadrant abdominal
      pain and left leg pain. Of significant note was the presence of constipation and
      urinary frequency over the preceding 8 months. Physical examination was normal.
      Magnetic resonance imaging of the lumbosacral spine revealed large perineural
      cysts eroding the sacrum and extending to the pelvis. The presence of abdominal
      symptoms prompted a neurosurgical consultation. However, after considering the
      possible risks associated with the surgical procedure, the patient opted to
      follow the nonsurgical route. RESULT AND CONCLUSIONS: Although commonly
      visualized, sacral perineural cysts are rarely symptomatic. When symptomatic, it
      may be secondary to its size and location. Presence of abdominal pain in a
      patient with back and/or leg pain should prompt the evaluation of the lumbosacral
      spine.

PMID- 14589194
TI  - Scoliosis associated with lumbar spondylolisthesis: a case presentation and
      review of the literature.
AB  - BACKGROUND CONTEXT: The association between scoliosis and spondylolisthesis is
      well documented, but criteria and methods for managing the deformity in patients
      with debilitating pain are not clear. PURPOSE: To describe correction of
      scoliosis by internal fixation of the spondylolisthesis. STUDY DESIGN: Case
      report of a patient with scoliosis developing in association with
      spondylolisthesis. METHODS: A 17-year-old female presented with a 6-month history
      of back and leg pain. No spinal curvature was noted in radiographs taken at the
      onset of symptoms. Significant curvature appeared during the 6-month history of
      pain in association with an L5-S1 spondylolisthesis. The spondylolisthesis was
      repaired with posterior pedicle screw instrumentation. RESULTS: The pain and the
      spinal curvature almost completely resolved after surgery, and the outcome
      remained excellent 14 months after surgery. CONCLUSION: In the properly diagnosed
      patient, surgical repair of the spondylolisthesis can relieve pain and correct
      spinal curvature.

PMID- 14589196
TI  - The case for cumulative trauma in low back disorders.

PMID- 14589197
TI  - Adolescent idiopathic scoliosis, bracing, and the Hueter-Volkmann principle.
AB  - BACKGROUND CONTEXT: Evidence demonstrating the biomechanical effects of the
      Hueter-Volkmann principle on vertebral body growth in spinal deformities is
      lacking. Bracing a scoliotic curve should, in theory, unload the growth plates on
      the concave side of the vertebral bodies near the curve's apex. Growth
      stimulation, leading to structural remodeling of the vertebral bodies, on the
      curve's concave side may explain the improvement or lack of curve progression, as
      measured by Cobb angles, reported with successful brace management of adolescent
      idiopathic scoliosis (AIS). PURPOSE: To determine whether brace treatment
      stimulated asymmetric chondrogenesis in the apical three vertebral bodies. STUDY
      DESIGN: A prospective cohort of patients with AIS receiving brace treatment were
      followed from the initiation of brace treatment until skeletal maturity. Patients
      were then retrospectively divided into those with and without radiographic
      progression. This post hoc analysis was included to determine risk factors for
      curve progression. PATIENT SAMPLE: Forty-one skeletally immature patients with
      AIS meeting criteria for brace treatment were followed until skeletal maturity.
      All patients were treated with thoracolumbosacral orthotics (TLSOs). OUTCOME
      MEASURES: The positional derotation of the TLSO on the spine was measured by
      comparing the initial radiograph with the first radiograph in a brace. The long
      term structural changes of the vertebral bodies were determined by comparing the
      initial and final radiographs. Differences in initial radiographic parameters
      between the groups of patients with AIS with and without curve progression
      indicated predictive factors for successful brace treatment. METHODS: Initial
      radiographic measurements were compared with those observed in a brace and those
      observed at final follow-up. The same analysis was retrospectively repeated
      comparing patients with AIS with and without radiographic progression. RESULTS:
      Cobb measurements (p=.0001) and concave-to-convex height ratios of the apical
      three vertebral bodies improved when the brace was initially applied (p=.0035).
      Structural remodeling or a rotational correction of the apical three vertebral
      bodies was appreciated only in patients with flexible curves (p=.01). CONCLUSION:
      Brace application results in immediate positional derotations of the spine in
      patients with AIS. These positional derotations were maintained only in patients
      with flexible curves, at final follow-up. Brace treatment was not recommended in
      patients whose curves did not correct at least 20% in a TLSO.

PMID- 14589199
TI  - Achievement of normal sagittal plane alignment using a wedged carbon fiber
      reinforced polymer fusion cage in treatment of spondylolisthesis.
AB  - BACKGROUND CONTEXT: Previous clinical studies of interbody fusion cages have
      generally failed to report sagittal plane alignment. In some cases, parallel
      sided cages have contributed to loss of lumbar lordosis. A wedged-shaped carbon
      fiber-reinforced polymer (CFRP) cage implant filled with autologous bone was
      designed to allow surgeons to more easily achieve normal sagittal plane alignment
      in posterior lumbar interbody fusion (PLIF). PURPOSE: This study was conducted to
      test the safety and efficacy of the wedged CFRP cage and the ability of surgeons
      to achieve normal anatomic alignment using an implant of this shape. STUDY
      DESIGN/SETTING: The wedged CFRP cage with pedicle screw fixation was evaluated in
      the treatment of patients with spondylolisthesis in a 2-year prospective study
      performed at 12 centers under a Food and Drug Administration (FDA)-approved
      protocol PATIENT SAMPLE: Inclusion criteria included patients with isthmic or
      degenerative spondylolisthesis at a single level below L4 with a translational
      malalignment of 3 mm or greater. Exclusion criteria included patients with more
      than 90% translation, previous surgery or abnormalities at more than two levels.
      OUTCOME MEASURES: Traditional outcome measures have included clinical success
      (improvement in pain and function) and fusion success (proof of living bone
      bridging the fusion area). This study adds a more complete analysis of anatomic
      success (restoration or maintenance of normal disc space height and sagittal
      plane alignment). METHODS: A clinical study of PLIF with pedicle screw fixation
      included a prospective group of 46 patients treated for spondylolisthesis. This
      article presents the data from the FDA-approval protocol. RESULTS: Fusion success
      was achieved in 35 of 36 patients (97.2%) reaching the 2-year follow-up interval.
      Clinical success was achieved in 35 of 37 (94.6%), and overall success was
      achieved in 33 of 36 (91.2%). Disc space height averaged 8.3 mm preoperatively,
      was increased to 10.2 mm at surgery and was maintained at 9.8 mm at 2 years. L4
      S1 sagittal plane alignment was maintained within normal range, averaging 30.6
      degrees after surgery. Clinical and fusion success rates trended higher than
      previous results with the rectangular cage but were not statistically different.
      Fusion success was significantly better than prior literature for treatment of
      spondylolisthesis (p=.0160). Complications of the surgery trended lower but were
      not statistically different from the study of the rectangular cage. CONCLUSIONS:
      The wedged CFRP cage with pedicle screw fixation allows surgeons to maintain
      normal sagittal plane alignment. These devices are safe and effective for
      treatment of spondylolisthesis and are FDA approved in the United States.

PMID- 14589201
TI  - Spinal reflex excitability changes after cervical and lumbar spinal manipulation:
      a comparative study.
AB  - BACKGROUND CONTEXT: Spinal manipulation (SM) is a commonly employed nonoperative
      treatment modality in the management of patients with neck, low back or pelvic
      pain. One basic physiologic response to SM is a transient decrease in motoneuron
      activity as assessed using the Hoffmann reflex (H-reflex) technique. Previous
      research from our laboratory indicates that both SM with a high-velocity, low
      amplitude thrust and mobilization without thrust produced a profound but
      transient attenuation of motoneuronal activity of the lumbosacral spine in
      asymptomatic subjects. To date, effects of cervical SM procedures on the
      excitability cervical motoneuron pools are unknown. PURPOSE: The objective of
      this research was to a gain a more complete understanding of the physiologic
      effects of SM procedures on motoneuron activity, by comparing the effects of
      regional SM on cervical and lumbar motoneuron pool excitability. STUDY
      DESIGN/SETTING: Maximal H-reflex amplitudes were recorded before and after SM in
      both the cervical and lumbar regions of asymptomatic subjects in two successive
      experimental sessions. PATIENT SAMPLE: Asymptomatic, young healthy volunteers
      were used in this study. OUTCOME MEASURES: Changes in flexor carpi radialis and
      gastrocnemius H-reflex amplitudes before and after SM procedures. METHODS: H
      reflexes recorded form the tibial and median nerves were evaluated before and
      after lumbar and cervical SM, respectively. RESULTS: Both Lumbar and cervical SM
      produced a transient but significant attenuation of motoneuron excitability. The
      attenuation of the tibial nerve H-reflex amplitude was proportionately greater
      than that of the median nerve, which occurred after cervical SM. CONCLUSIONS: SM
      procedures lead to transient suppression of motoneuron excitability, as assessed
      by the H-reflex technique. Lumbar spine SM appears to lead to greater attenuation
      of motoneuron activity compared with that of the cervical region. Thus, these two
      distinct regions of the spine may possess different responsiveness levels to
      spinal manipulative therapy.

PMID- 14589200
TI  - Gender-related differences in treatment outcomes for patients with
      musculoskeletal disorders.
AB  - BACKGROUND CONTEXT: Clinicians have long hypothesized that gender may be a risk
      factor in treatment outcomes of patients with chronic disability associated with
      musculoskeletal disorders. Although the scientific literature shows a higher
      prevalence of occupational low back injury in men, and a higher rate of
      repetitive motion and neck injuries in women, few studies have comprehensively
      investigated the role of gender regarding cost-related outcome variables of
      significance after work-related injuries. PURPOSE: This study was designed to
      examine the relationship between gender and biopsychosocial treatment outcomes in
      a predominately chronically disabled spinal disorder (CDSD) workers' compensation
      cohort undergoing a tertiary functional restoration program. STUDY DESIGN: A
      prospective comparison cohort study investigating the effect of gender on
      biopsychosocial treatment outcomes as risk factors for rehabilitation failure.
      PATIENT SAMPLE: A cohort of 1,827 consecutively treated patients with CDSD were
      placed into two gender-based groups: men (n=1,158, average age 40.7+/-10 years)
      and women (n=669, average age 42.5+/-10 years). OUTCOME MEASURES: Before the
      start of the program, and again upon completion of the program, all patients
      received a standard psychosocial assessment and were assessed on a variety of
      physical factors (leading to a cumulative score, calculated on the basis of the
      aggregates and averages of these physical measures). A structured clinical
      interview examining socioeconomic outcomes was conducted at 1 year after program
      completion, and at least partial information was obtained from this interview on
      all patients in the present study. METHODS: All patients underwent a medically
      directed functional restoration program combining quantitatively guided exercise
      progression with a multimodal disability management approach using psychological
      and case management techniques. RESULTS: Men had a significantly higher rate of
      lumbar injury than women, whereas women had a significantly higher rate of
      cervical injury. Men returned to work and retained work at a 40 hours/week job at
      a higher rate at 1-year follow-up. Women evidenced a higher rate of health care
      seeking behaviors from new providers. On physical testing immediately after
      treatment, men had a significantly higher cumulative physical score (gender
      normalized), both before and after treatment. On depression and disability
      questionnaires, men showed fewer pre- and posttreatment depressive symptoms with
      lower pretreatment disability scores. CONCLUSIONS: The present study represents
      the first large-scale examination of the relationship between gender and
      treatment outcomes for a population with CDSD after work injuries. There was a
      pattern of moderately better 1-year posttreatment socioeconomic outcome for men.
      On psychosocial measures, men showed lower disability and depression scores than
      women, with higher levels of physical functioning both before and after
      treatment. Overall, male patients with CDSD appeared to show somewhat better
      biopsychosocial outcomes. This leaves the question of identifying gender-specific
      risk factors to explain these differences.

PMID- 14589202
TI  - Anterior thoracic scoliosis constructs: effect of rod diameter and intervertebral
      cages on multi-segmental construct stability.
AB  - BACKGROUND CONTEXT: Many studies have reported on the use of anterior
      instrumentation for thoracolumbar scoliosis and more recently thoracic scoliosis.
      However, the optimal construct design remains an issue of debate. PURPOSE: To
      optimize construct design and enhance implant survival until a successful spinal
      arthrodesis is achieved. STUDY DESIGN: This study evaluated the effect of rod
      diameter and intervertebral cages on construct stiffness and rod strain using a
      long-segment, anterior thoracic scoliosis model with varying levels of
      intervertebral reconstruction. METHODS: Sixteen fresh-frozen calf spine specimens
      (T1 to L1) were divided into two groups based on rod diameter reconstruction (4
      mm and 5 mm). Testing included axial compression, anterior flexion, extension and
      lateral bending with variations in the number and level of intervertebral cage
      reconstructions: apical disc (one), end discs (two), apical and end discs
      (three), all seven levels (seven). Multisegmental construct stiffness and rod
      strain were determined and normalized to the intact specimen for analysis.
      RESULTS: The seven-level intervertebral cage construct showed significantly
      greater stiffness in axial compression for both the 4-mm (366% increased
      stiffness) and 5-mm (607% increased stiffness) rod groups (p<.001). The remaining
      constructs were not significantly different from each other (p>.05). In flexion,
      similar results were obtained for the 4-mm construct (p<.001) but not the 5-mm
      construct, because the reconstruction-alone, one-, two- and three-cage constructs
      were all significantly stiffer than the intact specimen (p<.05). Multisegmental
      construct stiffness under extension loading, as well as right and left lateral
      bending, also exhibited significant differences between the seven-level interbody
      cage reconstructions and the remaining constructs. Apical rod strain for both the
      4-mm-rod and 5-mm-rod groups were significantly higher for the two cage
      constructs (a cage at either end but not the apex where the strain gauges were
      located) as compared with the other constructs (p<.05). These differences were
      more pronounced in the 4-mm-rod group. Similar results were obtained in anterior
      flexion, extension and lateral bending. CONCLUSIONS: Intervertebral cages at
      every level significantly improved construct stiffness compared with increasing
      rod diameter alone. Moreover, cages markedly decreased rod strain, and when
      structural interbody supports were not used, axial compression created the
      greatest rod strain.

PMID- 14589203
TI  - Biochemical injection treatment for discogenic low back pain: a pilot study.
AB  - BACKGROUND CONTEXT: Biochemical treatment options including attempts at
      intervertebral disc restoration are desirable for the physiologic treatment of
      degenerative disc disease. PURPOSE: This was a pilot study to test the potential
      effectiveness of intradiscal injection therapy using agents known to induce
      proteoglycan synthesis in the treatment of intervertebral disc disease. STUDY
      DESIGN: Prospective, within subject, experimental design was applied in the
      study. PATIENT SAMPLE: Thirty patients, average age 46.5 years, with chronic
      intractable low back pain of 8.5 years average duration, took part in the study.
      All patients had lumbar discography with reproduction of pain. OUTCOME MEASURES:
      Pretreatment Roland-Morris disability scores and visual analogue scores were
      compared with 1-year follow-up posttest values of these scores. METHODS: Lumbar
      intervertebral discs were injected with a solution of glucosamine and chondroitin
      sulfate combined with hypertonic dextrose and dimethlysulfoxide (DMSO).
      Assessment of pain and disability was completed before treatment and an average
      of 12 months after the last treatment. RESULTS: Posttreatment Roland-Morris
      scores for the entire group of 30 patients of 6.4+/-.994 were significantly
      (p<.001) lower than pretreatment scores of 12.0+/-.92 (mean+/-SE). The
      posttreatment visual analogue scores of 3.00+/-.44 were also significantly less
      than the pretreatment of 6.11+/-.33 (mean+/-SE). Although the results were
      statistically significant for the 30 patients as a whole, 17 of the 30 patients
      (57%) improved markedly with an average of 72% improvement in disability scores
      and 76% in visual analogue scores. The other 13 patients (43%) had little or no
      improvement. Patients who did poorly included those with failed spinal surgery,
      spinal stenosis and long-term disability. There were no complications or serious
      side effects, although postinjection pain was moderate to severe for 48 to 72
      hours and required epidural steroids in five cases. CONCLUSIONS: The results of
      this pilot study suggest that intradiscal injection therapy with glucosamine,
      chondroitin sulfate, hypertonic dextrose and DMSO warrants further evaluation
      with randomized controlled trials.

PMID- 14589204
TI  - The use of bioabsorbable implants in the spine.
AB  - BACKGROUND CONTEXT: Bioabsorbable implants are commonplace in sports medicine
      surgeries, especially in shoulder and knee ligamentous reconstruction. Their use
      is now expanding to the realm of spinal reconstructive surgery. Newer polymers
      offer reduced incidence of the side effects of aseptic sterile sinus formation
      and have appropriate resorption time parameters for spine use. These new
      bioabsorbable materials confer initial and intermediate-term stability that is
      adequate for stable bony healing in various applications. The majority of human
      clinical applications in the spine that have been documented involve bone graft
      harvest site reconstruction, posterior spinal graft containment, anterior
      interbody reconstruction and anterior cervical and lumbar spine tension band
      plating. PURPOSE: The purpose of this review article is to highlight the
      indications and outcomes of the use of bioabsorbable implants in specific spinal
      applications. STUDY DESIGN: A comprehensive literature review of the English and
      non-English literature on bioabsorbable implant technology. METHODS: A
      comprehensive literature review was performed to gather basic science, animal and
      human data on the use of bioabsorbable implants in spinal surgery. RESULTS:
      Bioabsorbable implants have demonstrated strength and resorption characteristics
      commensurate with the physiologic and biomechanical requirements of the human
      spinal axis. Histologic sampling has demonstrated successful time-patterned
      resorption accompanied by bony replacement and remodeling of intervertebral cage
      devices in the animal model. CONCLUSION: Bioresorbable compounds appear to have a
      role in specific spinal reconstructive procedures. Their radiolucent nature
      improves image assessment of fusion healing, and their time-engineered resorption
      characteristics allow controlled dynamization in interbody and plate
      applications. Their widespread use and acceptance may increase dramatically as
      further research and clinical studies report on their safety and efficacy.

PMID- 14589205
TI  - Hip spine syndrome: management of coexisting radiculopathy and arthritis of the
      lower extremity.
AB  - BACKGROUND CONTEXT: Significant lumbar spinal stenosis and lower extremity
      arthritis may coexist in the elderly. This combination of lumbar stenosis with
      radiculopathy and lower extremity arthritis may lead to diagnostic uncertainty.
      PURPOSE: To describe the findings of hip spine syndrome, a constellation of
      symptoms with extensive overlap of radiculopathy and lower extremity arthritis.
      CONCLUSIONS: Evaluation of the patient with lower extremity pain in consideration
      for total joint arthroplasty should include functional inquiry of the spinal
      nerves. Diagnostic tests and injections may allow an informative weighting of the
      patient's symptoms, leading to a better understanding of the patient's pain
      syndrome. There is a group of patients who have a total hip arthroplasty and then
      develop or may continue to have pain of groin and buttock, secondary to sciatica
      of lumbar spinal stenosis. For the patient undergoing total hip arthroplasty with
      asymptomatic spinal stenosis, there may be increased neurological risk at
      surgery, related to the stenosis. The patient with both conditions may require
      surgical decompression of the lumbar stenosis as well as joint arthroplasty of
      the arthritic joint.

PMID- 14589206
TI  - Lumbar intervertebral disc cyst as a cause of radiculopathy.
AB  - BACKGROUND CONTEXT: Lumbar radiculopathy is commonly caused by degenerative
      conditions such as a herniated disc or lumbar spinal stenosis. Less common
      etiologies include intraspinal extradural masses such as synovial cysts and gas
      containing ganglion cysts. Intraspinal extradural cysts that communicate with the
      intervertebral disc are a rare entity and thus, an uncommon cause of lumbar
      radiculopathy. There are only ten cases of an intervertebral disc cyst reported
      in the literature. PURPOSE: To document the first reported case of an
      intervertebral disc cyst in North America. Two series of Japanese patients with
      intervertebral disc cyst confirmed radiographically and intraoperatively have
      recently been reported. STUDY DESIGN: A case report of an intervertebral disc
      cyst at L4-5 causing an L5 radiculopathy. OUTCOME MEASURES: Japanese Orthopaedic
      Association score for low back pain. METHODS: The patient and the authors
      involved in the patient's management were interviewed. All medical records,
      radiographic imaging studies, intraoperative findings, and pertinent literature
      were also reviewed. RESULTS: Preoperative magnetic resonance imaging (MRI) scan
      demonstrated a well-localized cyst compressing the ventral aspect of the thecal
      sac at L4-L5. Discography and subsequent computed tomographic (CT) scanning
      demonstrated the cyst communicating with an intervertebral disc herniation via an
      annular rupture. Decompressive discectomy and surgical excision of the disc cyst
      from the spinal canal resulted in complete recovery and resolution of the
      preoperative radiculopathy. Clinical improvement was documented using the JOA
      scoring system. Patient's preoperative score was 4/15, and postoperative score
      was 15/15. CONCLUSION: Although exceedingly rare, an intervertebral disc cyst
      should remain in the differential diagnosis of any extradural intraspinal mass
      ventral to the thecal sac. Diagnosis of an intervertebral disc cyst requires
      recognition of this uncommon entity and a high index of suspicion. Discography
      and post-discography computerized tomography (CT) scan confirm the diagnosis.
      Operative treatment includes decompression, and excision of the cyst and is
      reserved only for cases in which the cyst results in clinical symptoms
      unresponsive to nonoperative management.

PMID- 14589209
TI  - Comment on "Greater trochanteric pain syndrome in patients referred to orthopedic
      spine specialists".

PMID- 14589212
TI  - Radiograph assessment for patients with low back pain.

PMID- 14589213
TI  - Magnetic resonance imaging: use in patients with low back pain or radicular pain.

PMID- 14589214
TI  - Lumbar discography.
AB  - STUDY DESIGN: A comprehensive review of the literature dealing with lumbar
      discography was conducted. OBJECTIVE: The purpose of the review is to update the
      North American Spine Society position statement published in 1994 that addressed
      criticisms of lumbar discography, to identify indications for SUMMARY OF
      BACKGROUND DATA: Lumbar discography remains a controversial diagnostic procedure.
      There are concerns about its safety and clinical value, although many support its
      use in specific applications. METHODS: Articles dealing with lumbar discography
      were reviewed and are summarized in this report. RESULTS: Most of the recent
      literature supports the use of discography in selected patients. Although not to
      be taken lightly, many of the serious complications and high complication rates
      reported before 1970 have decreased since then because of improvement in
      injection technique, imaging and contrast materials. CONCLUSIONS: Most of the
      current literature supports the use of discography in select situations.
      Indications for discography include, but are not limited to: (1) Further
      evaluation of demonstrably abnormal discs to help assess the extent of
      abnormality or correlation of the abnormality with the clinical symptoms. Such
      symptoms may include recurrent pain from a previously operated disc and lateral
      disc herniation. (2) Patients with persistent, severe symptoms in whom other
      diagnostic tests have failed to reveal clear confirmation of a suspected disc as
      the source of pain. (3) Assessment of patients who have failed to respond to
      surgical intervention to determine if there is painful pseudarthrosis or a
      symptomatic disc in a posteriorly fused segment and to help evaluate possible
      recurrent disc herniation. (4) Assessment of discs before fusion to determine if
      the discs within the proposed fusion segment are symptomatic and to determine if
      discs adjacent to this segment are normal. (5) Assessment of candidates for
      minimally invasive surgical intervention to confirm a contained disc herniation
      or to investigate dye distribution pattern before chemonucleolysis or
      percutaneous procedures. Lumbar discography should be performed by those well
      experienced with the procedure and in sterile conditions with a double-needle
      technique and fluoroscopic imaging for proper needle placement. Information
      assessed and recorded should include the volume of contrast injected, pain
      response, with particular emphasis on its locations and similarity to clinical
      symptoms, and the pattern of dye distribution. Frequently, discography is
      followed by axial computed tomography scanning to obtain more information about
      the condition of the disc.

PMID- 14589215
TI  - Spine rehabilitation: secondary and tertiary nonoperative care.

PMID- 14589216
TI  - Lumbar epidural steroid injections.

PMID- 14589217
TI  - Open discectomy as treatment for herniated nucleus pulposus of the lumbar spine.

PMID- 14589218
TI  - Lumbar zygapophysial (facet) joint injections.

PMID- 14589219
TI  - Arthroscopic microdiscectomy.

PMID- 14589220
TI  - Are specialty society-based treatment guidelines still relevant?

PMID- 14589221
TI  - Gender influences on spine loads during complex lifting.
AB  - BACKGROUND CONTEXT: Previous research has documented differences in spine loading
      between genders when the imposed load is normalized relative to the size of the
      person. However, under realistic work conditions the magnitude of the load
      handled is seldom adjusted relative to worker anthropometry. Thus, there is a
      void in our knowledge in that we do not understand how material handling
      influences spine loading and potential risk of injury as a function of gender
      under realistic lifting situations. PURPOSE: To evaluate the differences in spine
      loading between men and women when exposed to similar workplace demands. STUDY
      DESIGN: A laboratory study was conducted to investigate the biomechanical
      responses during realistic free-dynamic lifting tasks when subjects lifted from
      origins and destinations that were either fixed or set relative to the subject's
      anthropometry. PATIENT SAMPLE: Twenty men and 20 women asymptomatic for low back
      pain were recruited to participate in the study. OUTCOME MEASURES: The three
      dimensional spine loads were predicted from a well-established electromyography
      assisted model. METHODS: Both genders completed a series of symmetric and
      asymmetric (60-degree clockwise) lifts that originated from two shelf heights
      ("relative" to knee height and "set" at 35 cm from floor) and terminated at one
      of two destination heights ("relative" to waist and "set" 102 cm from the floor).
      Three levels of box weight were investigated (6.8, 13.6 and 22.7 kg). RESULTS:
      Men had significantly greater compression forces than women (about 640 N).
      Loading differences between genders were further magnified by several of the
      workplace factors. The differences between men and women were even greater when
      lifting either of the heavier loads from the lower fixed shelf (more than 50%
      greater). CONCLUSIONS: It is apparent that men produce the greater loads on their
      spines during lifting. However, engineering controls, such as adjustable
      workplace layout or less weight lifted, may reduce or eliminate gender-specific
      differences in spine loads. Furthermore, the differences in spine loads appear to
      be a result of kinematic trade-offs and muscle coactivity differences in
      combination with unequal body masses between genders. However, when the loads
      were put into context of the expected tolerances of the spine, women were found
      to be at increased risk of injury, especially when lifting heavy loads or under
      asymmetric lifting conditions. Collectively, the results indicate the need to
      account for differences between the genders when designing the workplace.

PMID- 14589222
TI  - Microscopic lumbar discectomy results for 60 cases in professional and Olympic
      athletes.
AB  - BACKGROUND CONTEXT: There is no documented information indicating time for return
      to play after lumbar discectomy in professional and Olympic athletes. PURPOSE: To
      determine the rate of return to sport and the average time of recovery in elite
      athletes undergoing microscopic lumbar discectomy (MLD). STUDY DESIGN: Between
      1984 and 1998, the senior author performed 60 MLDs on 59 professional and Olympic
      athletes with lumbar herniated nucleus pulposus. PATIENT SAMPLE: Sixty
      consecutive MLDs performed on professional and Olympic athletes were reviewed.
      OUTCOME MEASURES: The rate of return and the average time to return to sport were
      determined. Also, the distribution of pain and presence of neurologic deficits
      were recorded. METHODS: A retrospective review was performed. RESULTS: Follow-up
      indicated that all but 7 of the 60 cases had returned to their sport, including
      one who underwent a second MLD for a herniation at an adjacent level. The average
      time from surgery to return was 5.2 months for the entire group, with a range of
      1 to 15 months. CONCLUSION: MLD was effective in correcting the problems that
      forced the athletes to seek help, and the time to return often depends on factors
      other than their medical condition. Postoperatively, a complete trunk
      stabilization rehabilitation program was effective in returning these athletes to
      a high level of competition.

PMID- 14589224
TI  - Cervical plates: comparison of physical characteristics and in vitro pushout
      strength.
AB  - BACKGROUND CONTEXT: There are many cervical plates available to the spine surgeon
      today. A single plate design may not be appropriate for every clinical situation.
      It is important for the surgeon to understand the differences of these plating
      systems. Plate systems are known to fail by screw pullout from the bone, screw
      and plate breakage and a less frequent but clinically observed screw pushout from
      the plate. Pushout testing of the screws from the plate have not previously been
      subjected to study. PURPOSE: This compares the features of cervical plating
      systems and the strength of the locking mechanisms to allow the surgeon to make a
      knowledgeable choice of plating system. STUDY DESIGN: This is a review of
      descriptive geometric characteristics of cervical plate systems and a
      biomechanical evaluation of locking mechanism screw pushout strength. METHODS:
      Physical characteristics of each plate were determined. Features of plates and
      screws were cataloged. Each of the test plate systems had a different locking
      mechanism. Biomechanical testing of the locking mechanism-screw-plate constructs
      was performed to determine the pushout strength of the fixation screw from the
      plate-locking mechanism. RESULTS: Physical characteristics of the plating
      systems, including lengths, widths, shortest screw lengths and distance from edge
      of plate to nearest screw, were determined. Biomechanical testing showed
      significant differences in pushout strength, in part explained by the type of
      locking mechanism. CONCLUSIONS: Biomechanical screw pushout data demonstrate that
      a significant range of pushout strengths exist across the available cervical
      plate systems today. Knowing the physical characteristics of the cervical plating
      systems available may allow the selection of a plate best suited for a given
      clinical situation.

PMID- 14589223
TI  - Anterior cervical fusion: a comparison of cage, dowel and dowel-plate constructs.
AB  - BACKGROUND CONTEXT: Threaded lumbar cages have been used as a safe and effective
      surgical fusion method for a decade. Smaller versions have now been developed for
      the cervical spine to obviate the need for allograft use or iliac autograft
      harvest and to provide initial stability before fusion. PURPOSE: To compare
      anterior cervical interbody fusion with the BAK/C Cervical Interbody Fusion
      System, cage (Centerpulse Spine-Tech Inc., Minneapolis, MN), conventional
      anterior cervical discectomy and fusion (ACDF) and plate constructs (anterior
      cervical locking plates). STUDY DESIGN/SETTING: Radiological and clinical
      outcomes of patients who underwent cervical fusion with the BAK/C (filled with
      local autograft reamings) are compared with ACDF and plate fusion constructs
      (anterior cervical locking plates). One surgeon performed 88 fusions: BAK/C
      (n=30), ACDF (n=32), plate (n=26). There were 43 one-level and 45 two-level
      fusions from C3-C4 to C7-T1. PATIENT SAMPLE: The patients represented a wide
      range of diagnoses as indications for cervical fusion. Patients (n=88) were 40
      men (45%) and 48 women (55%) with a mean age of 51 years (range, 30 to 70 years).
      Thirty-five percent of patients were smokers, and 26% had known workers' or other
      compensation issues. OUTCOME MEASURES: Hospital records were examined for data
      from operative reports and discharge summaries. An independent spine radiologist
      performed a radiological review of cervical flexion and extension films, noting
      fusion status, graft position and cage subsidence. Short Form (SF)-36 inventories
      for physical/mental functioning and visual analog scales (VAS) for pain were
      administered. METHODS: A retrospective clinical and radiological review was
      performed. Hospital and clinic chart data, flexion-extension X-rays and self
      assessments (SF-36, VAS) were evaluated. Follow-up at X-ray was 2.4 years (range,
      1.0 to 5.5 years). RESULTS: Iliac crest harvesting was least likely for BAK/C
      patients (2 of 30; 6.7%) compared with ACDF (30 of 32; 93.8%) and plate patients
      (13 of 26; 50.0%; p<.0001). Plate surgeries took longest (3.5 hours), followed by
      ACDF (2.3 hours) and BAK/C (2.2 hours; p<.0001). Blood loss was greatest for
      plate procedures (289 cc), followed by BAK/C (142 cc) and ACDF (121 cc; p<.01).
      No BAK/C patient stayed in the hospital more than 1 day; ACDF, 1 to 2 days;
      plate, 1 to 5 days (p<.02). BAK/C patients were most likely to have a successful
      fusion: BAK/C, 29 of 30, 97%; ACDF, 26 of 31, 84% (one X-ray fusion status
      indeterminate); plate, 22 of 26, 85% (p<.0585). No BAK/C patient experienced
      prolonged donor-site pain (0%) compared with ACDF (25.0%) and plate (23.0%)
      patients. SF-36 and VAS scores, influenced by compensation, were comparable for
      all groups. Revisions were as follows: ACDF, 4 of 32, 13%; plate, 2 of 26, 8%);
      BAK/C, 1 of 30, 3%). CONCLUSIONS: In this study, the BAK/C cage group had the
      lowest graft requirements/risks, generally required fewer hospital resources,
      achieved similar patient outcomes and fused at a higher rate than ACDF and plate
      groups.

PMID- 14589226
TI  - Delayed postoperative spinal epidural hematomas.
AB  - BACKGROUND CONTEXT: Symptomatic epidural hematomas after spinal surgery are
      uncommon and are usually diagnosed within 24 hours after surgery. PURPOSE: We
      report a series of delayed epidural hematomas in a subset of patients who awoke
      from surgery neurologically unchanged and then deteriorated more than 3 days
      after their index procedure. The goals of this report are to outline the clinical
      presentation, radiological characteristics and outcome of this uncommon entity.
      STUDY DESIGN/SETTING: We retrospectively reviewed the database of six spine
      surgeons over a 4-year period, looking for presence of epidural hematomas as a
      cause of clinical deterioration after an asymptomatic postoperative period of at
      least 3 days. PATIENT SAMPLE: We identified a subset of patients who awoke from
      surgery neurologically unchanged and then deteriorated more than 3 days after
      spinal surgery. A total of 4,018 patients were identified over the 4-year period
      of review. OUTCOME MEASURES: Presence of spinal epidural hematoma as a cause of
      clinical deterioration after an asymptomatic period of at least 3 days. The
      medical records, including the history, physical, preoperative and postoperative
      neurological examinations, as well as plain radiographs and magnetic resonance
      images, were reviewed. METHODS: We retrospectively reviewed the database of six
      spine surgeons over a 4-year period. We looked for delayed spinal epidural
      hematomas as a cause of clinical deterioration after an asymptomatic
      postoperative period of at least 3 days. We examined potential risk factors for
      spinal extradural hematomas. RESULTS: Of 4,018 patients, we identified seven with
      spinal epidural hematoma who presented more than 3 days after their index
      procedure. The initial presenting symptom, which heralded the subsequent onset of
      neurological deterioration, consisted of severe sharp pain with radiation to the
      extremities. The average time to neurological deterioration was 5.3 days. Fifty
      seven percent of the patients had multiple previous spinal surgeries at the site
      of the epidural hematoma. Surgical evacuation of the epidural hematomas resulted
      in neurological improvement in five patients. Persistent neurological deficits
      were observed in two patients. CONCLUSION: Delayed spinal epidural hematomas are
      an uncommon cause of delayed deterioration after spinal surgery. Previous surgery
      with attendant scarring that results in impairment of clot resorption may be a
      contributing factor in the development of the condition.

PMID- 14589227
TI  - A surgical revisitation of Pott distemper of the spine.
AB  - BACKGROUND CONTEXT: Pott disease and tuberculosis have been with humans for
      countless millennia. Before the mid-twentieth century, the treatment of
      tuberculous spondylitis was primarily supportive and typically resulted in dismal
      neurological, functional and cosmetic outcomes. The contemporary development of
      effective antituberculous medications, imaging modalities, anesthesia, operative
      techniques and spinal instrumentation resulted in quantum improvements in the
      diagnosis, management and outcome of spinal tuberculosis. With the successful
      treatment of tuberculosis worldwide, interest in Pott disease has faded from the
      surgical forefront over the last 20 years. With the recent unchecked global
      pandemic of human immunodeficiency virus, the number of tuberculosis and
      secondary spondylitis cases is again increasing at an alarming rate. A surgical
      revisitation of Pott disease is thus essential to prepare spinal surgeons for
      this impending resurgence of tuberculosis. PURPOSE: To revisit the numerous
      treatment modalities for Pott disease and their outcomes. From this information,
      a critical reappraisal of surgical nuances with regard to decision making,
      timing, operative approach, graft types and the use of instrumentation were
      conducted. STUDY DESIGN: A concise review of the diagnosis, management and
      surgical treatment of Pott disease. METHODS: A broad review of the literature was
      conducted with a particular focus on the different surgical treatment modalities
      for Pott disease and their outcomes regarding neurological deficit, kyphosis and
      spinal stability. RESULTS: Whereas a variety of management schemes have been used
      for the debridement and reconstruction of tuberculous spondylitis, there has also
      been a spectrum of outcomes regarding neurological function and deformity.
      Medical treatment alone remains the cornerstone of therapy for the majority of
      Pott disease cases. Surgical intervention should be limited primarily to cases of
      severe or progressive deformity and/or neurological deficit. Based on the
      available evidence, radical ventral debridement and grafting appears to provide
      reproducibly good long-term neurological outcomes. Furthermore, recurrence of
      infection is lowest with such techniques. Posterior operative techniques are most
      effective in the reduction and prevention of spinal deformity. CONCLUSIONS:
      Unlike historical times, effective medical and surgical management of tuberculous
      spondyitis is now possible. Proper selection of drug therapy and operative
      modalities, however, is needed to optimize functional outcomes for each
      individual case of Pott disease.

PMID- 14589229
TI  - The role of repeated end-range/pain response assessment in the management of
      symptomatic lumbar discs.
AB  - BACKGROUND CONTEXT: The selection of appropriate patients for lumbar disc surgery
      is a challenging task involving a highly variable, multifactorial decision
      process complicated by a lack of reliable, validated clinical signs and imaging
      findings. Recently, multiple studies have demonstrated the reliability and
      diagnostic utility of a standardized form of spinal assessment using repeated end
      range test movements while monitoring patterns of pain response (McKenzie
      assessment). PURPOSE: It is the aim of this article to evaluate the utility of
      this assessment system and its literature support in the selection of candidates
      for surgery for disc-related pain. STUDY DESIGN AND METHODS: A literature review.
      RESULTS: Most patients under consideration for lumbar disc surgery, when examined
      using this form of dynamic mechanical spinal evaluation, based on patients'
      patterns of pain response to standardized repeated end-range lumbar test
      movements and positions, fall into one of three subgroups: 1) a reversible
      condition, 2) an irreversible condition or 3) an unaffected condition. Reversible
      conditions in acute to chronic low back and/or leg pain are recoverable, often
      rapidly so, using nonoperative self-care dictated by the patient's assessment
      findings. The elicitation of pain "centralization," an improvement (favorable
      change) in pain location in response to repetitive end-range testing, typically
      occurring with only one direction of test movement(s), predicts a high likelihood
      of successful response to conservative care, even in the presence of neurologic
      deficits. Irreversible conditions are characterized by symptom aggravation by all
      directions of testing, including the absence of the centralization response,
      predicting a poor response to nonsurgical care. In those whose pain is unaffected
      with similar testing, evidence indicates the pain is likely nondiscogenic. A
      dynamic disc model has been described as a possible model for these varying pain
      responses. Insight into annular integrity of symptomatic discs is also provided
      using this repeated end-range/pain response (McKenzie) assessment. CONCLUSIONS:
      As described, the literature supports the use of a repeated end-range/pain
      response assessment (dynamic mechanical evaluation) in obtaining diagnostic and
      therapeutic information in patients with low back and leg pain. This may
      contribute to improving the selection process of surgical patients.

PMID- 14589231
TI  - Bone graft substitutes for spinal fusion.

PMID- 14589232
TI  - Failure of posterior titanium atlantoaxial cable fixation.
AB  - BACKGROUND CONTEXT: The operative treatment of rotatory atlantoaxial instability
      remains controversial. The use of cable fixation has largely replaced the use of
      wire for interlaminar fixation. Although cable fixation offers biomechanical
      advantages over wire fixation, it is still at risk of fatigue failure. The
      authors were unable to locate any published reports of fatigue failure of
      titanium cables in the fixation of atlantoaxial instability. PURPOSE: The purpose
      of this case study is to describe an unusual case of fatigue failure of a
      titanium cable used to aid in atlantoaxial fusion for the treatment of rotatory
      atlantoaxial instability. STUDY DESIGN: Case study. METHODS: We reviewed the
      medical records and X-rays of a patient with rotatory atlantoaxial instability
      treated with posterior C1-C2 fusion and atlantoaxial fixation with a titanium
      multistranded cable, who developed fracture of the cable and migration of the
      cable into the spinal canal. RESULTS: The patient was revised with removal of the
      broken cable, repair of the pseudarthrosis and fixation with atlantoaxial screws.
      CONCLUSION: Interlaminar fixation with cables or wires is at risk for failure
      with potential migration of the wire or cable into the spinal canal. The authors
      found that failure of the cables or wire can be salvaged with application of
      transarticular screws.

PMID- 14589234
TI  - Spontaneous regression of herniated cervical disc.
AB  - BACKGROUND CONTEXT: Spontaneous regression of herniated lumbar disc has been well
      established. However, spontaneous regression of herniated cervical disc is rare,
      and such reports are few. PURPOSE: To present a rare case of spontaneous
      regression of herniated cervical disc. STUDY DESIGN: A case study. METHODS: A 27
      year-old man presented with severe pain on the left C6 level. Magnetic resonance
      imaging (MRI) revealed a lateral extruded disc at the C5-C6 level. The patient
      refused discectomy. RESULTS: The patient's pain disappeared after 3 weeks. Follow
      up MRI revealed partial spontaneous regression in the extruded disc after 3 weeks
      and complete spontaneous regression after 12 months. CONCLUSION: All previous
      cases of herniated cervical disc that regressed spontaneously have been of the
      extruded type. In the patient with the cervical extruded disc, nonsurgical
      conservative observation should be considered an option for treatment.

PMID- 14589236
TI  - The future of spine care and the evolving role of physician as advocate.

PMID- 14589235
TI  - From the Electrodiagnostics Lab.

PMID- 14589238
TI  - A plea for professional behavior. North American Spine Society Presidential
      Address, Montreal, Canada, 2002.

PMID- 14589240
TI  - Role of calcineurin in calcium-mediated hypoxic injury to white matter.
AB  - BACKGROUND CONTEXT: Calcium influx into cells is responsible for initiating the
      "final pathway" to cell death in neuronal tissue after traumatic or hypoxic
      injury. The specific pathways in this cascade are myriad and the importance each
      one plays is controversial. It is clear, though, that blocking individual
      pathways confers protection to these tissues. PURPOSE: In the present study we
      examined the role of Cyclosporin A (CsA), FK-506 and rapamycin in modulating the
      effects of Ca(2+) influx through their interactions with immunophilins and
      specifically the end result of calcineurin modulation. METHODS: Dorsal columns
      were isolated from the spinal cord of adult rats and injured by exposure to
      hypoxic conditions for 60 minutes. The samples were monitored
      electrophysiologically in an in vitro recording chamber (maintained at 37 C
      degrees ) during injury, and the compound action potential (CAP) was monitored
      with glass microelectrodes. The dorsal column was exposed to hypoxic Ringers
      solution alone or with the different immunosuppressants and compared with
      baseline readings. Functional recovery of the dorsal column was then assessed by
      recovery of the CAP. RESULTS: The mean CAP decreased to about 20% of baseline
      control levels during hypoxia and returned 53.8+/-7.6% of baseline (p<.05) after
      reoxygenation. CsA, an immunosuppressant known to inhibit calcineurin, promoted a
      significantly greater recovery of CAP amplitude to 76.8+/-5.2% and 72.1+/-13.2%
      of control (p<.05) after hypoxic injury and reoxygenation of dorsal column white
      matter when applied at concentrations of 1 microM and 10 microM, respectively. FK
      506, which also inhibits calcineurin, was applied at a concentration of 0.1
      microM, and promoted CAP amplitude recovery to 82.6+/-5.0% of control after
      hypoxic injury and reoxygenation of dorsal column white matter. The addition of
      rapamycin (1 microM), which binds to the same immunophilin as FK-506, to the FK
      506 (0.1 microM) solution during hypoxic injury showed recovery of CAP amplitudes
      to only 56.9+/-6.7% of control. Electron microscopy revealed remarkable
      protection of axons and prevention of organelle disruption in segments treated
      with CsA and FK-506 during hypoxia when compared with hypoxic controls.
      CONCLUSION: In conclusion, both CsA and FK-506 confer in vitro protection to
      dorsal columns during hypoxic injury at physiological temperatures, and rapamycin
      blocks the protective effect of FK-506. Thus, calcineurin may play an important
      role in the physiology of neuronal injury.

PMID- 14589241
TI  - The effect of spinal instrumentation particulate wear debris. an in vivo rabbit
      model and applied clinical study of retrieved instrumentation cases.
AB  - STUDY DESIGN: The current study was undertaken to determine if the presence of
      spinal instrumentation wear particulate debris deleteriously influences early
      osseointegration of posterolateral bone graft or disrupts an established
      posterolateral fusion mass. OBJECTIVES: Using an in vivo animal model, the first
      phase (basic science) of this study was to evaluate the effect(s) of titanium
      wear particulate on a posterolateral spinal arthrodesis based on serological,
      histological and immunocytochemical analyses. The second phase (clinical) was to
      perform the same analysis of soft tissue surrounding spinal instrumentation in 12
      symptomatic clinical patients. SUMMARY OF BACKGROUND DATA: The effect of
      unintended wear particulate resulting from micromotion between the
      interconnection mechanisms in spinal instrumentation remains a clinical concern.
      METHODS: Thirty-four New Zealand White rabbits were randomized into two groups
      based on postoperative time periods of 2 months (Group 1, n=14) and 4 months
      (Group II, n=20). Group I underwent a posterolateral arthrodesis (PLF) at L5-L6
      using tricortical iliac autograft or tricortical iliac autograft plus titanium
      particulate. Group 2 all received iliac autograft at the initial surgery and were
      reoperated on after 8 weeks and treated with PLF exposure alone or titanium
      particulate. Postoperative analysis included serological quantification of
      systemic cytokines. Postmortem microradiographic, immunocytochemical and
      histopathological assessment of the intertransverse fusion mass quantified the
      extent of osteolysis, local proinflammatory cytokines, osteoclasts and
      inflammatory infiltrates. Clinical aspect of study: Over the last 2 years, 12
      patients more than 0.4 years after spinal instrumentation presented with painful
      paraspinal inflammation. At surgical exploration, the cultures were negative for
      infection and the surrounding soft tissue was examined for cytokine reactions.
      There was loosening of implants and osteolysis in the location of the wear debris
      in 8 of 12 patients. RESULTS: Basic science phase: serological analysis of
      systemic cytokines indicated no significant differences in cytokine levels
      (p>.05) between the titanium or autograft treatments. Immunocytochemistry
      indicated increased levels of local cytokines: TNF-alpha at the titanium-treated
      PLF sites at both time periods (p<.05). Osteoclast cell counts and regions of
      osteolytic resorption lacunae were higher in the titanium-treated versus
      autograft-alone groups (p<.05), and the extent of cellular apoptosis was markedly
      higher in the titanium-treated sites at both time intervals. Electron microscopy
      indicated definitive evidence of phagocytized titanium particles and foci of
      local, chronic inflammatory changes in the titanium-treated sites. Clinical
      aspect: Eleven of 12 clinical cases demonstrated elevated TNF-alpha levels and an
      increased osteoclastic response in the vicinity of wear debris caused by dry
      frictional wear particles of titanium or stainless steel. Osteolysis most
      commonly involved loose transverse connectors. Resection of the wear debris and
      surrounding fibroinflammatory glycocalyx resulted in resolution of clinical
      symptoms in all 12 cases. CONCLUSIONS: Titanium particulate debris introduced at
      the level of a spinal arthrodesis elicits a cytokine-mediated particulate-induced
      response favoring proinflammatory infiltrates, increased expression of
      intracellular TNF-alpha, increased osteoclastic activity and cellular apoptosis.
      This is the first basic scientific study and the first clinical study
      demonstrating associations of spinal instrumentation particulates wear debris and
      increased cytokines and increased osteoclastic activity. Osteolysis is the number
      one cause of failure of orthopedic implants in the appendicular skeleton. Spinal
      surgeons need to increase their awareness of this destructive process.

PMID- 14589243
TI  - Effect of intramedullary signal changes on the surgical outcome of patients with
      cervical spondylotic myelopathy.
AB  - BACKGROUND CONTEXT: Intramedullary signal intensity changes on magnetic resonance
      imaging (MRI) in cervical spondylotic myelopathy are thought to be indicative of
      the prognosis. However, the prognostic significance of signal intensity changes
      remains controversial. PURPOSE: To determine the radiographic and clinical
      factors that correlate with the prognosis after surgery in patients with cervical
      spondylotic myelopathy and to investigate the factors affecting the outcome of
      intramedullary signal changes on MRI. STUDY DESIGN: A prospective study
      evaluating clinical parameters and MRI in consecutive patients operated on for
      cervical spondylotic myelopathy. PATIENT SAMPLE: A total of 146 consecutive
      patients with cervical spondylotic myelopathy operated on during a 2-year period
      (September 1999 to September 2001) formed the study group. OUTCOME MEASURES: Age,
      duration of symptoms, number of cervical prolapsed intervertebral discs, surgical
      approach, preoperative signal changes, residual compression and postoperative
      outcome of signal changes; clinical outcome (motor, sensory, autonomic and
      disability improvement). METHODS: The participants in this study underwent
      anterior cervical discectomy/corpectomy or laminectomy/laminoplasty for cervical
      spondylotic myelopathy. Clinical features and MRI findings were studied in detail
      and compared with postoperative clinical and radiological status. The spinal cord
      signal intensity changes were evaluated before and after surgery. The
      multifactorial effect of such variables as age, duration of symptoms, number of
      prolapsed intervertebral discs, surgical approach (anterior/posterior),
      preoperative cord changes on T1- and T2-weighted sequences and
      persistence/regression of cord changes on clinical outcome
      (motor/sensory/autonomic/disability improvement) was studied using stepwise
      logistic regression. The highlight of the study is the analysis of the factors
      affecting regression of cord changes and their effect on postoperative outcome.
      RESULTS: Preoperative intramedullary signal changes were present in 121 of 146
      patients (82.9%); of these 121 patients, T1- and T2-weighted images were present
      in 81, and T2-weighted images were present in 40 (no patient had isolated T1
      change). Postoperative MRI could be obtained in 44 of 121 patients (36.4%) with
      preoperative intramedullary signal changes; 14 had regression of cord changes.
      There was no significant difference in the clinical presentation of patients with
      and without cord changes. There was a significant correlation between the
      surgical outcome of patients and their age, duration of symptoms, number of
      cervical prolapsed intervertebral discs, surgical approach, preoperative signal
      changes, residual compression and postoperative outcome of signal changes. The
      patients with no intramedullary signal changes and signal changes only on T2
      weighted images had a better outcome than patients with signal changes on both T1
      and T2-weighted images. The patients with regression of intramedullary signal
      changes had significantly better outcome. There was no significant correlation
      between regression of signal changes and other factors. However, chronicity of
      disease, multiplicity of discs and postoperative residual compression relatively
      affect persistence of intramedullary signal changes. CONCLUSIONS: The presence of
      intramedullary signal changes on T1- as well as T2-weighted sequences on MRI in
      patients with cervical spondylotic myelopathy indicates a poor prognosis.
      However, the T2 signal intensity changes reflect a broad spectrum of spinal cord
      reparative potentials. Predictors of surgical outcomes are preoperative signal
      intensity change patterns of the spinal cord and their postoperative
      persistence/regression on radiological evaluations, age at the time of surgery,
      multiplicity of involvement and chronicity of the disease and surgical approach
      (anterior/posterior).

PMID- 14589245
TI  - An electromyographic study of isokinetic axial rotation in young adults.
AB  - BACKGROUND CONTEXT: Trunk rotation is associated with over 60% of all low back
      injuries. However, there are gaps in the knowledge about trunk rotation. PURPOSE:
      To study the axial rotation torque and electromyographs (EMGs) of seven trunk
      muscles bilaterally in static and isokinetic modes with increasing angular
      velocity to determine qualitative and quantitative muscle response. STUDY DESIGN:
      An electromyographic study of seven trunk muscles bilaterally was carried out in
      50 normal subjects during static and isokinetic axial rotation at varying angular
      velocity. The qualitative and quantitative force and EMG measures were made and
      analyzed phenomenologically and statistically. METHODS: Fifty normal young adults
      (27 men, 23 women) performed an isometric maximal voluntary contraction (MVC)
      from the neutral upright-seated posture to their right and left. Also, these
      subjects performed isokinetic axial rotation from neutral seated position to
      right and left, and from prerotated right and left "end of range posture" toward
      the neutral at 10, 20 and 40 degrees per second angular velocity. All
      experimental trials were made on axial rotation tester designed for the study.
      EMG was recorded from the erector spinae at L3 and T10 vertebral levels,
      latissimus dorsi, pectoralis major, rectus abdominis and external and internal
      obliques bilaterally. The torque and EMG in isokinetic condition were normalized
      against those of isometric condition. Descriptive statistics were calculated.
      Data were subjected to analysis of variance, and torque was regressed on EMG.
      RESULTS: The peak isokinetic torques were significantly lower than the isometric
      torques (p<.01), but the EMGs of the isokinetic conditions were significantly
      higher than those of isometric trials (p<.01). The isokinetic axial rotation
      torque decreased by 1 Nm to 1.5 Nm with per degree increase in velocity of
      rotation, with the values for 10, 20 and 40 degrees per second angular velocities
      being significantly different (p<.01). There was a significant increase (p<.01)
      in percent EMG (up to 28%) per unit torque with increasing angular velocity of
      rotation. The rotation torque from prerotated position to neutral was
      significantly higher than that of rotation away from the neutral (p<.001). The
      EMG magnitude increased significantly with increasing velocity (2% to 17% at 10
      degrees per second), 21% to 28% at 20 degrees per second, 30% to 36% at 40
      degrees per second). Regression analysis revealed poor predictability of torque
      based on EMG. The latter was suggested because of the role and behavior of the
      ligaments and joint capsules of the spine. CONCLUSION: The axial rotation is
      initiated and maintained by the contralateral external obliques, ipsilateral
      latissimus dorsi and internal oblique. The ipsilateral erector spinae likely play
      a stabilizer role. The isometric torque is greater than the isokinetic, which
      decreases with increasing velocity. Even with decreasing torque, EMG
      progressively increases, indicating a disproportionally higher stress in the
      spinal connective tissues potentiating injury. The data presented here suggest
      that, for safety, load and velocity of rotation should be kept low.

PMID- 14589246
TI  - Use of ketorolac tromethamine in children undergoing scoliosis surgery. an
      analysis of complications.
AB  - BACKGROUND CONTEXT: Ketorolac Tromethamine (ketorolac) is a nonsteroidal anti
      inflammatory drug (NSAID) with proven efficacy in decreasing postoperative pain
      in various surgical settings, including the treatment of spine deformities.
      However, some studies have raised questions regarding the potential side effects
      of this agent, such as increased bleeding and inhibition of bony fusion. PURPOSE:
      This study was conducted to determine whether there is any association between
      the use of ketorolac and postoperative complications in a group of children who
      underwent scoliosis surgery. STUDY DESIGN/SETTING: This is a retrospective review
      of a group of children who underwent spinal fusion between 1989 to 1999 at our
      institution. PATIENT SAMPLE: Data on a total of 208 children were analyzed in
      this study. Sixty received ketorolac and 148 did not. OUTCOME MEASURES:
      Postoperative transfusion and reoperation rates were the two main outcome
      measures of interest. METHODS: A retrospective review of 208 children who
      underwent scoliosis surgery was conducted, with a focus on ketorolac use.
      Univariate analysis and logistic regression were used to quantify the
      determinants of postoperative complications. RESULTS: Our analyses detected no
      significant differences in a broad range of socioclinical variables between the
      two patient groups, including age at surgery, gender, type of scoliosis, surgical
      approach, use of erythropoietin, levels of curvature and degree of curvature.
      Analysis of complication rates focusing on postoperative transfusion and revision
      surgery showed that there were no significant differences between the two groups.
      CONCLUSIONS: In this retrospective study of 208 children undergoing spine
      surgery, postoperative use of ketorolac did not significantly increase
      complications, including transfusion and reoperation.

PMID- 14589248
TI  - Substance P-containing nerves within the human vertebral body. an
      immunohistochemical study of the basivertebral nerve.
AB  - BACKGROUND CONTENT: The basivertebral nerve provides innervation to the
      trabecular bone of the vertebral body. The function of this nerve is not known.
      PURPOSE: The study was undertaken to better define the anatomic origin of this
      intraosseous nerve and to determine if this nerve contains substance P. METHODS:
      The basivertebral nerve, which enters the vertebral body by means of the large
      posterior vascular foramen was studied anatomically by dissection and then
      histologically characterized. Sixty-two specimens of the basivertebral nerve were
      harvested from within the bone by microscopically aided dissection. Specimens
      were harvested from cervical, thoracic and lumbar vertebrae. These specimens were
      then stained for the presence of protein S-100 and substance P. RESULTS: All 62
      specimens stained positively for both S-100 and substance P. CONCLUSION: The
      presence of substance P within these nerves is strong evidence that these nerves
      have the potential to transmit signals of nociception. The basivertebral nerve
      may play a role in some forms of clinical back and neck pain.

PMID- 14589250
TI  - Cervical myelopathy. current diagnostic and treatment strategies.
AB  - Cervical myelopathy is a varied clinical syndromes resulting from spinal cord
      dysfunction. Underlying causes are numerous, but spondylosis at one or more
      levels is the most common etiology. Natural history studies have demonstrated a
      variable clinical course with gradual neurologic deterioration in a majority of
      patients. While prospective clinical comparisons are limited, existing literature
      suggests that operative management reliably arrests the progression of myelopathy
      and may lead to functional improvement in a majority of patients. The selection
      of surgical procedures must be carefully individualized based on specific
      clinical and radiographic factors. Whereas anterior decompression and fusion
      procedures at one or two motion segments have predictable results, procedures
      involving three or more levels are associated with increased morbidity. Newer
      techniques for the treatment of multilevel cervical myelopathy include anterior
      decompression with 360-degree fusion, hybrid corpectomy/anterior cervical
      discectomy and fusion techniques and the use of dynamic anterior cervical plates.
      An alternative technique for patients with a lordotic sagittal alignment is
      laminoplasty, which has a proven track record of long-term good to excellent
      results.

PMID- 14589251
TI  - Thoracic extruded disc mimicking spinal cord tumor.
AB  - BACKGROUND CONTEXT: Thoracic disc herniation is a rare condition. Distinguishing
      between a herniated disc and tumor for a lesion found at the thoracic level can
      be a diagnostic challenge. PURPOSE: To describe a case of thoracic disc
      herniation that mimicked a spinal cord tumor. STUDY DESIGN/SETTING: Case report
      and review of the literature.P ATIENT SAMPLE: Case report. OUTCOME MEASURES:
      Report of postoperative symptoms. METHODS/DESCRIPTION: A 54-year-old man was
      admitted to the hospital with progressively worsening weakness in both lower
      extremities, increased numbness of both lower extremities, pain radiating into
      his groin bilaterally and left foot drop. During a recent visit to his family
      physician, the patient's legs gave out and he collapsed. Physical examination
      revealed markedly increased tone in both extremities. Magnetic resonance images
      at T11-12 showed signal abnormality in the anterior extradural space, which
      extended posterior and inferior to the disc level to the left of midline. An
      extramedullary lesion found in the posterior spinal canal showed a low signal on
      T1 image and a high but heterogeneous signal on T2-weighted images. Preoperative
      diagnosis was neoplasm. A bilateral decompressive laminectomy was performed under
      operative magnification and ultrasonography. A large extruded disc was found that
      migrated from the ventral aspect around the thecal sac and into the dorsal
      aspect, which compressed the sac to the right. The extradural lesion was
      dissected off the surrounding thecal sac. Postoperatively, the patient underwent
      rehabilitation and is able to walk with only minimal weakness of both legs.
      CONCLUSIONS: Determining the diagnosis for thoracic spinal lesions, either disc
      herniation or tumor, is a diagnostic challenge.

PMID- 14589254
TI  - "Paraplegia after lumbosacral nerve root block. report of three cases", by Houten
      JK, et al.

PMID- 14589253
TI  - Bone morphogenetic proteins BMPs. Letter.

PMID- 14589255
TI  - "Iatrogenic vertebral artery injury during anterior cervical spine surgery", by
      Dr. Burke JP, et al.

PMID- 14589256
TI  - The impact of treatment confidence on pain and related disability among patients
      with low-back pain: results from the University of California, Los Angeles, low
      back pain study.
AB  - BACKGROUND CONTEXT: Although many researchers and practitioners believe that
      patients' positive expectations of their treatment favorably influence clinical
      outcomes, there is little scientific evidence to support this belief. PURPOSE: To
      describe the level of patients' initial confidence in the success of their
      assigned treatment, by treatment group and other factors; and to estimate the
      effects of treatment confidence on subsequent changes in low-back pain and
      related disability. STUDY DESIGN AND PATIENT SAMPLE: Randomized clinical trial
      involving 681 patients treated for low-back pain in a managed-care facility in
      Southern California. OUTCOME MEASURES: Treatment confidence; and changes in three
      clinical measures of low-back pain: average pain, most severe pain and back-pain
      related disability. METHODS: Patients were randomly assigned to one of four
      treatment groups: medical care with and without physical therapy, and
      chiropractic care with and without physical modalities. Information was collected
      by questionnaires at baseline, 2 weeks, 6 weeks and 6 months. Treatment
      confidence was measured just after randomization on a scale of 0 to 10. RESULTS:
      Treatment confidence was lowest, on average, for patients assigned to medical
      care only and highest for patients assigned to medical care plus physical
      therapy. Other predictors of high treatment confidence were having acute pain and
      being older, female and nonwhite. Although treatment confidence was only weakly
      associated with subsequent changes in low-back pain or disability in the total
      sample, high treatment confidence was associated with greater improvement among
      patients assigned to medical care plus physical therapy. CONCLUSIONS: Initial
      confidence in treatment for low-back pain varies by type of care and other
      factors. Higher confidence may have some beneficial effect on the course of low
      back pain in certain patients, but this effect may depend on the type of
      interaction between client and provider.

PMID- 14589260
TI  - Comparison of short- and long-term outcomes for aggressive spine rehabilitation
      delivered two versus three times per week.
AB  - BACKGROUND CONTEXT: Rehabilitation services using intensive exercise for the
      treatment of chronic spinal pain have traditionally been scheduled at a frequency
      of three times per week. PURPOSE: In an attempt to reduce the cost of
      rehabilitation services, this study was designed to determine whether treatment
      offered two times per week could produce similar outcomes when compared with an
      established three times per week spine therapy program. STUDY DESIGN: Prospective
      cohort study. PATIENT SAMPLE: Seventy-seven consecutive patients with chronic
      spinal pain were treated with aggressive spine rehabilitation either two or three
      times per week. OUTCOME MEASURES: Flexibility, trunk strength and lifting
      capacity were quantified before and after treatment. Pain visual analog scores
      and Oswestry disability scores were measured before and after treatment, as well
      as 12 months after treatment. METHODS: A two times per week physical therapy
      program was developed to be identical in its treatment method to an established
      three times per week, group-oriented physical therapy program used for the
      treatment of chronic spinal pain. Patients with spinal pain who continued to work
      despite chronic pain complaints were allowed to choose between the two therapy
      programs based on availability of treatment slots and convenience. Treatment
      consisted of non-pain contingent quota-based exercises targeting identified
      physical impairments. Treatment sessions lasted for 2 hours and consisted of 30
      minutes of stretching, 30 minutes of low-impact step aerobics class and 1 hour of
      exercise on strength and endurance equipment. Therapy occurred in groups
      consisting of a maximum of eight patients who were closely supervised by two
      therapists. Targeted treatment time was 6 weeks. At 12 months after treatment,
      subjects were surveyed by mailed questionnaires. RESULTS: Seventy-seven patients
      with chronic spinal pain with a mean duration of symptoms of 32 months underwent
      treatment. Twenty-four subjects opted for the twice per week and 53 opted for the
      three times per week treatment. Seventy-one percent of subjects responded to the
      12-month follow-up questionnaire. Physical and self-reported measures improved
      with both treatment frequencies. There were no differences in outcomes between
      treatment frequencies for measured flexibility, trunk strength, lifting capacity,
      pain intensity scores or Oswestry scores at the completion of treatment. At 12
      month follow-up, no differences were noted between treatment frequencies for pain
      scores, Oswestry scores, patients' perceptions of adequacy of treatment,
      posttreatment exercise compliance or use of other treatments for their spinal
      problem. Total therapy visits were less in the two than three times per week
      groups (12 vs 15 visits). CONCLUSION: Similar outcomes were obtained from
      aggressive spine rehabilitation occurring two versus three times per week in
      patients presenting with moderate levels of chronic spinal pain. Reduction in
      physical therapy services and therefore cost did not adversely affect clinical
      outcomes in the treatment of this patient population.

PMID- 14589262
TI  - Comparing outcomes of anterior cervical discectomy and fusion in workman's versus
      non-workman's compensation population.
AB  - BACKGROUND CONTEXT: Anterior cervical discectomy and fusion (ACDF) is an accepted
      surgical procedure to treat degenerative conditions, including disc herniations
      and spinal stenosis. The literature on lumbar spine surgery reports that patients
      with a workman's compensation claim have less successful clinical results.
      Regarding the cervical spine, however, different conclusions have been drawn.
      PURPOSE: The purpose of this study was to directly compare the functional
      outcomes of ACDF in patients with and without a workman's compensation claim and
      to determine whether a compensation claim adversely affected the clinical
      outcome. STUDY DESIGN: This is a retrospective study examining the long-term
      results of ACDF in the workman's and non-workman's compensation populations.
      PATIENT SAMPLE: Eighty consecutive patients undergoing ACDF were retrospectively
      analyzed. The patients were divided into two groups: 30 patients in Group 1
      (workman's compensation) and 50 patients in Group 2 (non-workman's compensation).
      The average age of Group 1 was 45 years (range, 31 to 57) and Group 2 was 45
      years (range, 30 to 79). The patients were followed for an average length of 4
      years (range, 2 to 7 years). OUTCOME MEASURES: We evaluated the surgical results
      using a functional outcome scoring system (Odom's Criteria), visual analog scale
      and a radiographic grading scale. The questionnaire was independently
      administered in a standard question-answer format at the 1-year follow-up.
      Statistical analyses was performed using a Levene's test. METHODS: All surgeries
      were performed by the same attending physician. A left-sided approach and Smith
      Robinson fusion technique with autograft or allograft without instrumentation was
      used in all cases. A hard cervical orthosis was used postoperatively for 8 weeks.
      Radiographic examination including lateral flexion and extension views were
      obtained at a minimum of 12 months postoperatively. Furthermore, radiographic
      analysis was performed each subsequent postoperative year. The radiographs were
      analyzed by two independent physicians in a blind fashion for evidence of
      radiographic fusion. RESULTS: At follow-up no discernible difference was noted
      for functional outcomes. Eighty-three percent of patients in Group 1 and 90% of
      patients in Group 2 noted excellent or good results. This was not statistically
      significant (p=.280). In Group 1, 97% of patients returned to work at an average
      of 18 weeks, whereas 98% of patients in Group 2 returned to work at an average of
      10 weeks postoperatively. Upon radiographic evaluation, 64% of patients in Group
      1 were determined to have a solid fusion (Grade 3). The fusion rate in Group 2
      was 72%. This was not statistically significant. However, the fusion rate among
      smokers was 50%, and among nonsmokers it was 80%. This was statistically
      significant (p=.001). CONCLUSIONS: Workman's compensation claims did not
      adversely affect the functional outcome of ACDF. It should be noted that a
      significant increase in pseudarthroses was noted with the smoking population.
      Patient selection is a critical factor in determining functional outcome, with
      83% good to excellent results if the pathology, clinical presentation and
      radiographic findings correlate

PMID- 14589264
TI  - Vibratory loading decreases extracellular matrix and matrix metalloproteinase
      gene expression in rabbit annulus cells.
AB  - BACKGROUND CONTEXT: Whole body vibration is an important factor contributing to
      low back and radicular pain. Vibratory loading as a mechanical stimulus is
      transferred to connective tissues as energy from ground reaction forces, as well
      as a direct input from the use of motorized tools and vehicles. Extracellular
      matrix degradation parallels increased age and mechanical stimuli resulting in
      disc degeneration and eventual spinal deformity. PURPOSE: The objective of this
      study was to investigate the relationship between vibratory loading and
      extracellular matrix expression in cultured rabbit annulus cells. STUDY
      DESIGN/SETTING: An in vitro rabbit model using cultured annulus fibrosis cells
      isolated from normal intervertebral disc was used to study matrix and
      metalloproteinase expression in response to vibration. METHODS: Annulus fibrosis
      cells were isolated by collagenase digestion from New Zealand White rabbits.
      Vibratory stimulation was applied to annulus cells in vitro, using an oscillating
      platform to deliver 0.1 x gravity load at 6 Hz for 2, 4, 6 or 8 hours. Gene
      expression was assessed by reverse transcriptase polymerase chain reaction.
      RESULTS: Aggrecan, collagen Type III and matrix metalloproteinase-3 gene
      expression was suppressed by vibratory loading in rabbit annulus cells.
      Suppression of the aggrecan gene might lead to a decrease in proteoglycan
      synthesis. CONCLUSIONS: These data suggest that vibratory load may play an
      important role in extracellular matrix metabolism of intervertebral disc cells,
      especially in the gene expression pathway of proteoglycans. It has been proposed
      that vibratory loading increases production of matrix-degrading, proteolytic
      enzymes. We have demonstrated that gene expression for key matrix messages and
      matrix metalloproteinase is decreased by vibration. In conclusion, we believe
      that study of the roles between extracellular matrix gene suppression and
      mechanical stress may clarify the pathomechanism of disc degeneration, such as
      disc herniation or degeneration.

PMID- 14589266
TI  - Measurements of lumbopelvic lordosis using the pelvic radius technique as it
      correlates with sagittal spinal balance and sacral translation.
AB  - BACKGROUND CONTEXT: Maintenance of normal lumbar lordosis is important in the
      treatment of spinal disorders. Many attempts have been made to quantify normal
      sagittal spinal alignment and lordosis using a C7 plumb line and segmental
      angulations of the spinal vertebrae. Little attention has been given to pelvic
      compensation as it correlates to lumbar lordosis and overall sagittal spinal
      alignment. Better methods of measuring lordosis, which correlate with sagittal
      spinal balance and pelvic compensation, are needed in treating patients with
      spinal disorders. PURPOSE: To determine the correlation between lumbopelvic
      lordosis, pelvic rotation and sagittal spinal balance and standardize a method
      for measuring lumbopelvic lordosis, sacral translation, and sagittal spinal
      alignment. STUDY DESIGN: Sagittal alignments using the C7 plumb line, Cobb
      angles, sacral plumb line and the pelvic radius (PR) technique were used to
      measure standing 36-inch lateral radiographs of patients with various spinal
      disorders. PATIENT SAMPLE: A review of the records identified 62 patients with
      various spinal pathologies presenting to the (RGW) spine clinic that had standing
      lateral spine radiographs. Only radiographs that allowed positive identification
      of the C7 vertebral body, the entire thoracolumbar spine, the sacrum and both
      femoral heads were studied. These criteria allowed inclusion of 28 subjects in
      this study. The final population had 12 women and 16 men with an average age of
      52 years (SD, 16.6 years; range, 20 to 84 years). OUTCOME MEASURES: No outcomes
      measures were used in this study. METHODS: Measurements for sagittal spinal
      balance and lumbopelvic lordosis were made on 36-inch standing lateral
      radiographs of adult patients. Measurements included the C7 plumb line, segmental
      angulations of spinal vertebrae (Cobb angles), sacral translation and the PR
      technique for lumbopelvic lordosis. Data were analyzed for significant
      correlation between lumbopelvic lordosis, sagittal spinal balance, sacral
      translation and total segmental lumbar lordosis using the Cobb method. RESULTS:
      Our population averaged 50 degrees of total segmental lumbar lordosis from L1 to
      S1 (SD, 14.3; maximum, 89.5; minimum, 17.9). Nearly 75% of total segmental lumbar
      lordosis measured from L1 to S1 can be accounted for through the L4 to S1
      superior end plates and 47% through L5 to S1 superior end plates in our
      population. Total segmental lumbar lordosis correlated with total thoracic
      kyphosis (r=0.45, p=.008). Total segmental lumbar lordosis measured by the Cobb
      method significantly correlated with sagittal spinal balance (r=-0.35, p=.022)
      and sacral translation (r=0.41, p=.016). Measurements for lumbopelvic lordosis
      significantly correlated with sagittal spinal balance (r=-0.33, p=.042), sacral
      translation (r=-0.70, p=.00002) and total segmental lumbar lordosis (r=0.82,
      p<.000001). Measurements for sacral translation and sagittal spinal balance also
      correlated significantly (r=0.35, p=.034). CONCLUSIONS: Sacral translation, the
      C7 plumb line and lumbopelvic lordosis are useful measures for sagittal spinal
      balance. Lumbopelvic lordosis and sacral translation can be correlated to the
      sagittal spinal balance. Understanding these measurements and the range of
      lumbopelvic compensation can be extremely helpful in treating patients with
      spinal pathology and in avoidance of flatback deformity. Application of these
      measures would be especially helpful in the treatment of patients with spinal
      fusion, degenerative spondylosis, disc disease, fractures, and in the prevention
      of sagittal malalignment.

PMID- 14589267
TI  - Anatomic consideration for standard and modified techniques of cervical lateral
      mass screw placement.
AB  - BACKGROUND CONTEXT: Posterior screw placement techniques have been previously
      described. Each technique differs with respect to starting point, lateral
      angulation and sagittal orientation. PURPOSE: To examine the potential for injury
      to critical anatomic structures, such as nerve roots and vertebral arteries,
      during posterior cervical screw placement and to determine safe screw placement.
      STUDY DESIGN/SETTING: An anatomic study was conducted to determine the optimal
      screw angulation for posterior cervical lateral mass screws. SPECIMEN SAMPLE: Ten
      fresh-frozen human cadaveric cervical spine specimens were used, consisting of
      four females and six males, ranging in age from 32 to 68 years. OUTCOME MEASURES:
      Angular measurements and distance from nerve root and vertebral arteries were
      measured with a single caliper and recorded. One millimeter of proximity to a
      vital structure was considered a violation of that structure. METHODS: Ten fresh
      frozen human cadaveric cervical spine specimens were instrumented from C2 to C7
      by a single surgeon. Kirschner wires (2.0 mm) were used to reproduce the Roy
      Camille, Anderson and Magerl screw trajectories. The wire was drilled through
      each lateral mass, simulating overdrill error. Each technique was instrumented
      according to the original description and with additional modifications. The
      modification consisted of varying the angle of screw placement in the axial plane
      of the original description from 0 to 30 degrees. Distances to the closest
      neurovascular structures were averaged for all assays. RESULTS: The Magerl
      technique is safe at the standard position and modified positions of 20 degrees
      and 30 degrees from C3-C6. The Roy-Camille technique frequently violates
      neurovascular structures below C3, especially the nerve root with more lateral
      screw angulation. The standard technique is noted to have good bone purchase only
      at C2 and C3. The Anderson technique is safe at 20 degrees and 30 degrees
      modified positions from C3-C7. Posterior screw placement at the C7 vertebral
      level was safe only with a modified Anderson technique of 20 degrees and 30
      degrees of lateral screw angulation. CONCLUSIONS: The present study indicates
      that there are significant differences of potential neurovascular injury, which
      is dependent on the technique used for screw entry, the level instrumented and
      the angle of screw trajectory in the parasagittal plane.

PMID- 14589269
TI  - Diagnosis and surgical management of cervical ossification of the posterior
      longitudinal ligament.
AB  - BACKGROUND CONTEXT: The diagnosis and treatment of multilevel cervical
      ossification of the posterior longitudinal ligament (OPLL) is continuing to
      evolve as its effects become more readily recognized and surgical alternatives
      expand. PURPOSE: To review the clinical, neurodiagnostic and surgical management
      of OPLL. STUDY DESIGN/SETTING: Patients with early OPLL, often in their mid
      forties, present with radiculopathy or mild/moderate myelopathy.
      Radiographically, hypertrophy of the posterior longitudinal ligament with
      punctate ossification appears opposite multiple disc spaces. Patients with
      classic OPLL frequently become symptomatic in their mid-fifties with radiographic
      characteristics showing ossification of the ligament behind the vertebrae alone
      (segmental), behind the vertebrae including the intervertebral disc spaces
      (continuous), and combinations of the segmental and continuous variants and OPLL
      opposite disc spaces alone. Both magnetic resonance imaging (MRI) and computed
      tomography (CT) examinations are critical. MRI better delineates the extent of
      soft tissue abnormalities in three dimensions, including the cervicothoracic
      junction, whereas CT more readily identifies the foci of frank ossification.
      Surgical alternatives include anterior, posterior or combined approaches.
      Anterior surgical options include plated multilevel anterior discectomy and
      fusion, anterior cervical corpectomy with fusion (ACF), or plated multilevel ACF
      with differing posterior fusion techniques. Posterior surgical options vary from
      laminectomy with or without simultaneous fusion and laminoplasty. Although
      outcomes with different approaches vary, many direct anterior resection
      techniques achieve more favorable results because of appropriate and adequate
      resection of the ligament. CONCLUSIONS: The clinical and neuroradiographic
      documentation of OPLL and its appropriate surgical management anteriorly,
      posteriorly or circumferentially remain a therapeutic challenge.

PMID- 14589270
TI  - Techniques in cervical laminoplasty.
AB  - BACKGROUND CONTEXT: Laminoplasty provides an alternative to anterior procedures
      or multilevel laminectomy for patients with multilevel spinal stenosis and
      myeloradiculopathy. PURPOSE: To review the techniques, results and complications
      of cervical laminoplasty. STUDY DESIGN: The three basic variations of
      laminoplasty are the single open door, the French door or midline and the Z
      plasty technique. These techniques and their outcome are discussed in detail.
      RESULTS: The recovery rate after laminoplasty ranges from 50% to 70% without
      statistical superiority of any one technique over another. Closure of opened
      laminae, temporary nerve root deficit, decreased neck range of motion and axial
      pain are the main complications of laminoplasty. CONCLUSIONS: Good to excellent
      long-term clinical results can be expected for the appropriately selected
      patients regardless of the specific technique used.

PMID- 14589273
TI  - Artificial intervertebral discs and beyond: a North American Spine Society Annual
      Meeting symposium.
AB  - BACKGROUND CONTENT: This is a synopsis of a symposium presented to the North
      American Spine Society Annual Meeting in Seattle, WA, 2001. PURPOSE: To bring to
      the reader who may not have attended the symposium a distillation of the material
      presented on this frontier of spinal surgery. METHODS: Panel presentation.
      RESULTS: The proposed indication for artificial disc replacement is a degenerated
      but contained disc, painful to the point of major life-style interruption,
      refractory to at least 1 year of nonoperative treatment, preferably at a single
      lumbar level and without infection, listhesis or major facet joint disease or
      spinal stenosis. Total disc replacements have been developed and used mostly in
      Europe. Disc nucleus replacements have also been developed. No disc replacement
      has been approved for general use in North America as yet. The US Food and Drug
      Administration is conducting investigational device exemption studies at this
      time. CONCLUSIONS: Artificial disc replacement is not a new concept, the first
      attempts having been done in the early 1950s. During the past 15 years,
      considerable advance has been made with large numbers of patients, mostly in
      Europe, having surgery with either total disc prostheses or disc nucleus
      replacements. Only with truly scientific studies using patient randomization, pre
      and postsurgery outcome analyses by unbiased independent observers and
      statistical analysis by independent experts will the real value of these devices
      be realized.

PMID- 14589275
TI  - Spine in the arts.

PMID- 14589272
TI  - Management of respiratory compromise caused by cervical osteophytes: a case
      report and review of the literature.
AB  - BACKGROUND CONTEXT: Diffuse idiopathic skeletal hyperostosis (DISH) is a common
      condition in the aging spine. DISH is associated with large anterior osteophytes
      of the cervical spine, which can cause complications by compressing adjoining
      structures. Dysphagia is reported in up to 28% of patients, but respiratory
      compromise is rare. There have been no published recommendations for treatment.
      PURPOSE: To report that resection of cervical osteophytes, without cervical
      fusion, can be successful in the treatment of severe respiratory distress. STUDY
      DESIGN: This report describes the management of a patient with DISH and severe
      respiratory distress resulting from large anterior cervical osteophytes. METHODS:
      A team approach was used with collaboration between the orthopedic spine surgeons
      and the otolaryngologists. RESULTS: This patient was found to have compression of
      her posterior pharyngeal wall by the osteophytes. Tracheostomy was required for
      the management of the airway. The patient was dependent on the tracheostomy until
      the osteophytes were resected. The patient was then able to breathe normally.
      Treatment recommendations were developed based on this case of osteophyte-induced
      respiratory compromise as well as the previously published accounts of osteophyte
      induced dysphagia. CONCLUSIONS: Airway obstruction resulting from DISH can be
      treated according to the same principles as dysphagia resulting from DISH:
      surgical excision of osteophytes if conservative support fails.

PMID- 14589276
TI  - The spine patient.

PMID- 14589461
TI  - Cochrane collaboration-based reviews of health-care interventions: are they
      unequivocal and valid scientifically, or simply nihilistic?

PMID- 14589462
TI  - Intradiscal pressure and kinematic behavior of lumbar spine after bilateral
      laminotomy and laminectomy.
AB  - BACKGROUND CONTEXT: Bilateral laminotomy has been proposed as an alternative to
      laminectomy for decompression of lumbar spinal stenosis. Preservation of the
      posterior midline ligaments with laminotomy is presumed to maintain spinal
      segment stability. There have been no previous studies that directly compare the
      amount of destabilization and increase in disc pressures between the two
      procedures. PURPOSE: To quantify spinal segmental instability caused by bilateral
      laminotomy and laminectomy, and to compare the central and peripheral intradiscal
      pressures after the two procedures. STUDY DESIGN/SETTING: Mechanical testing of
      the lumbar motion segments of calf spines. METHODS: Nine fresh calf spines were
      tested under flexion, extension, lateral bending and axial rotation, intact
      first, then after laminotomy and laminectomy at the level of L4-L5. Four
      miniature pressure transducers were implanted in the central and peripheral disc
      at L4-L5 to measure intradiscal pressures. Three-dimensional motion was measured
      with motion analysis system. RESULTS: Comparing with bilateral laminotomy,
      laminectomy showed significant increase in segmental motion at the surgical level
      in flexion (16%, p<.05), extension (14%, p<.04) and right axial rotation (23%,
      p<.03). In flexion, the stress at the anterior annulus increased a nonsignificant
      20% after laminotomy, but significant 130% after laminectomy (p<.02). In the
      intact spine, the posterolateral annulus experienced the highest stress with
      lateral bending to the same side when compared with other loading directions.
      This stress remained unchanged after laminotomy but increased 9% after
      laminectomy (p<.06). In rotation, axial intradiscal stresses were evenly
      distributed and unchanged after each procedure. CONCLUSIONS: Laminectomy causes
      more destabilization of a spinal motion segment than laminotomy and significantly
      increases disc stress in the anterior annulus.

PMID- 14589463
TI  - Plain radiography of the lumbosacral spine in Marfan syndrome.
AB  - BACKGROUND CONTEXT: Marfan syndrome is a connective tissue disorder that results
      from a defect in the production of fibrillin. These patients tend to have several
      osseous anomalies of the lumbosacral spine. PURPOSE: This study examines the
      effectiveness of plain radiographic findings in predicting Marfan syndrome. STUDY
      DESIGN/SETTING: Case-control study. PATIENT SAMPLE: Fourteen height-matched
      controls and 33 patients with Marfan syndrome were obtained from our genetics
      clinic or through the National Marfan Foundation. OUTCOME MEASURES: Determined
      using measurements taken on plain radiographs. METHODS: Five measurements were
      acquired of the lumbosacral spine from the radiographs of both groups:
      interpedicular distance, scalloping value, sagittal canal diameter, vertebral
      body width and transverse process width. RESULTS: The following measurements were
      significantly larger in patients with Marfan syndrome: interpedicular distance at
      L1-L5 (p<.0001); sagittal diameters of the vertebral canal at L4-S2 (p<.01);
      transverse process to vertebral body width ratio at L2-L5 (p<.01). There was no
      significant difference in the scalloping values from L1-L5 between the patients
      with Marfan syndrome and the controls. A multivariate regression analysis
      generated the following criteria for plain film diagnosis of Marfan syndrome (two
      criteria need to be met for diagnosis): interpedicular distance at L5 greater
      than or equal to 36.0 mm, sagittal diameter at L5 greater than or equal to 13.5
      mm or transverse process to vertebral width ratio at L3 greater than or equal to
      2.25. CONCLUSION: Based on this criteria, patients can be diagnosed with Marfan
      syndrome with a high sensitivity (81.8%) but a low specificity (58.3%). Thus,
      plain radiography can be a useful means of screening patients with Marfan
      syndrome.

PMID- 14589464
TI  - Clinical perceptions of the risk of vertebral artery dissection after cervical
      manipulation: the effect of referral bias.
AB  - BACKGROUND CONTEXT: The growing recognition of cervical manipulation as a
      treatment of neck pain and cervicogenic headaches has lead to increased interest
      in potential complications that may result from this treatment approach. Recent
      surveys have reported that many neurologists will encounter cases of vertebral
      artery dissection that occur at various times after cervical manipulation,
      whereas most practitioners of spinal manipulation are of the opinion that these
      events are extremely rare. We asked the question whether these differences in
      perception could be explained in part by referral or selection bias. PURPOSE: To
      assess the effect of referral bias on the differences in perceived incidence of
      vertebral artery dissection after cervical manipulation between neurologists and
      chiropractors in Canada. STUDY DESIGN: This study was a retrospective review of
      cases where neurological symptoms consistent with cerebrovascular ischemia were
      reported by chiropractors in Canada. METHODS: An analysis of data from a
      chiropractic malpractice insurance carrier (Canadian Chiropractic Protective
      Association [CCPA]) and results of a survey of chiropractors was performed to
      determine the likelihood that a vertebral artery dissection after cervical
      manipulation would be reported to practicing chiropractors. This was compared
      with the likelihood that a neurologist would be made aware of such a
      complication. RESULTS: For the 10-year period 1988 to 1997, there were 23 cases
      of vertebral artery dissection after cervical manipulation reported to the CCPA
      that represents 85% of practicing chiropractors in Canada. Based on the survey,
      an estimated 134,466,765 cervical manipulations were performed during this 10
      year period. This gave a calculated rate of vertebral artery dissection after
      manipulation of 1:5,846,381 cervical manipulations. Based on the number of
      practicing chiropractors and neurologists during the period of this study, 1 of
      every 48 chiropractors and one of every two neurologists would have been made
      aware of a vascular complication from cervical manipulation that was reported to
      the CCPA during their practice lifetime. CONCLUSIONS: The perceived risk after
      cervical manipulation by chiropractors and neurologists is related to the
      probability that a practitioner will be made aware of such an incident. The
      difference in the number of chiropractors (approximately 3,840 in 1997) and
      neurologists (approximately 4,000 in 1997) in active practice and the fact that
      each patient who has a stroke after manipulation will likely be seen by only one
      chiropractor but by three or more neurologists partly explains the difference in
      experience and the perception of risk of these two professions. This selection or
      referral bias is important in shaping the clinical opinions of the various
      disciplines and distorts discussion on the true incidence of these complications
      of cervical manipulation. The nature of this study, however, describes the
      likelihood that a clinician will be made aware of such an event and cannot be
      interpreted as describing the actual risk of stroke after manipulation.

PMID- 14589465
TI  - Two-year follow-up of a controlled trial of intradiscal electrothermal
      anuloplasty for chronic low back pain resulting from internal disc disruption.
AB  - BACKGROUND: On the basis of observational data, intradiscal electrothermal
      anuloplasty (IDETA) has been implemented as a treatment for back pain resulting
      from internal disc disruption. PURPOSE: To assess the efficacy of IDETA. STUDY
      DESIGN: Prospective cohort study with comparison group and 2-year follow-up.
      PATIENT SAMPLE: Of 53 patients who satisfied the diagnostic criteria for internal
      disc disruption, 36 were allocated to a treatment group and 17 to a comparison
      group, according to whether their insurer approved treatment with IDETA. OUTCOME
      MEASURES: Outcomes were assessed in terms of relief of pain, return to work and
      use of opioids to treat persisting pain. METHODS: The treatment group underwent
      IDETA. The comparison group underwent a conventional rehabilitation program.
      Outcomes were assessed at 3 months, 12 months and 2 years after treatment.
      RESULTS: As a group, the comparison patients exhibited no significant improvement
      in their pain at any time. One was partially relieved, but no patient was
      completely relieved at either 12 or 24 months. The patients treated with IDETA
      exhibited significant improvements in their median pain scores, which were
      sustained at 12 and 24 months. At 24 months, 54% of these patients had achieved
      at least 50% relief of their pain, no longer used opioids and were at work. Seven
      patients (20%) were totally free of pain and at work at 24 months. CONCLUSIONS:
      The long-term results of IDETA are stable and enduring. It is not universally
      successful, but 54% of patients can reduce their pain by half, and one in five
      patients can expect to achieve complete relief of their pain.

PMID- 14589466
TI  - Return to play criteria for the athlete with cervical spine injuries resulting in
      stinger and transient quadriplegia/paresis.
AB  - BACKGROUND CONTEXT: Fortunately, catastrophic cervical spinal cord injuries are
      relatively uncommon during athletic participation. Stinger and transient
      quadriplegia/paresis are more frequent injuries that have a wide spectrum of
      clinical severity and disabilities. Although the diagnosis of these injuries may
      not be clinically difficult, the treatment and decision about when or if the
      athlete may return to play after such an injury is often unclear. PURPOSE: This
      article reviews the current literature to help determine reasonable guidelines
      for return-to-play criteria after cervical spine injuries in the athlete.
      METHODS: The contemporary English literature and experience-based guidelines for
      return to play after cervical spine injuries in the athlete were reviewed.
      RESULTS: Despite the frequency of cervical-related injuries among athletes
      participating in contact and collision sports, no consensus exists within the
      medical field as to a standard guideline approach for return to preinjury
      activity level. CONCLUSION: The issue of return to play for an athlete after a
      cervical spine injury is controversial. Tremendous extrinsic pressures may be
      exerted on the physician from noninvolved and involved parties. The decision to
      return an athlete to a particular sport should be based on the mechanism of
      injury, objective anatomical injury (as demonstrated by clinical examination and
      radiographic evaluation) and an athlete's recovery response.

PMID- 14589467
TI  - Neurophysiological effects of spinal manipulation.
AB  - BACKGROUND CONTEXT: Despite clinical evidence for the benefits of spinal
      manipulation and the apparent wide usage of it, the biological mechanisms
      underlying the effects of spinal manipulation are not known. Although this does
      not negate the clinical effects of spinal manipulation, it hinders acceptance by
      the wider scientific and health-care communities and hinders rational strategies
      for improving the delivery of spinal manipulation. PURPOSE: The purpose of this
      review article is to examine the neurophysiological basis for the effects of
      spinal manipulation. STUDY DESIGN: A review article discussing primarily basic
      science literature and clinically oriented basic science studies. METHODS: This
      review article draws primarily from the peer-reviewed literature available on
      Medline. Several textbook publications and reports are referenced. A theoretical
      model is presented describing the relationships between spinal manipulation,
      segmental biomechanics, the nervous system and end-organ physiology. Experimental
      data for these relationships are presented. RESULTS: Biomechanical changes caused
      by spinal manipulation are thought to have physiological consequences by means of
      their effects on the inflow of sensory information to the central nervous system.
      Muscle spindle afferents and Golgi tendon organ afferents are stimulated by
      spinal manipulation. Smaller-diameter sensory nerve fibers are likely activated,
      although this has not been demonstrated directly. Mechanical and chemical changes
      in the intervertebral foramen caused by a herniated intervertebral disc can
      affect the dorsal roots and dorsal root ganglia, but it is not known if spinal
      manipulation directly affects these changes. Individuals with herniated lumbar
      discs have shown clinical improvement in response to spinal manipulation. The
      phenomenon of central facilitation is known to increase the receptive field of
      central neurons, enabling either subthreshold or innocuous stimuli access to
      central pain pathways. Numerous studies show that spinal manipulation increases
      pain tolerance or its threshold. One mechanism underlying the effects of spinal
      manipulation may, therefore, be the manipulation's ability to alter central
      sensory processing by removing subthreshold mechanical or chemical stimuli from
      paraspinal tissues. Spinal manipulation is also thought to affect reflex neural
      outputs to both muscle and visceral organs. Substantial evidence demonstrates
      that spinal manipulation evokes paraspinal muscle reflexes and alters motoneuron
      excitability. The effects of spinal manipulation on these somatosomatic reflexes
      may be quite complex, producing excitatory and inhibitory effects. Whereas
      substantial information also shows that sensory input, especially noxious input,
      from paraspinal tissues can reflexively elicit sympathetic nerve activity,
      knowledge about spinal manipulation's effects on these reflexes and on end-organ
      function is more limited. CONCLUSIONS: A theoretical framework exists from which
      hypotheses about the neurophysiological effects of spinal manipulation can be
      developed. An experimental body of evidence exists indicating that spinal
      manipulation impacts primary afferent neurons from paraspinal tissues, the motor
      control system and pain processing. Experimental work in this area is warranted
      and should be encouraged to help better understand mechanisms underlying the
      therapeutic scope of spinal manipulation.

PMID- 14589468
TI  - Paraspinal denervation and the spinal degenerative cascade.
AB  - BACKGROUND CONTEXT: The aging of the spine has been reported to follow a
      degenerative cascade described by Kirkaldy-Willis. This cascade does not take
      into account the paraspinal muscles. Substantial recent knowledge of the anatomy,
      physiology and pathophysiology of the paraspinal muscles suggests that they
      should play a role in the degenerative cascade. Pain relates to paraspinal
      denervation in a number of disorders. Using new needle electromyographic
      technique, MiniPM, we may be able to quantify the extent of paraspinal muscle
      denervation. PURPOSE: To explore the potential interactions between paraspinal
      muscle denervation and the degenerative cascade. STUDY DESIGN: Literature review,
      reanalysis of a blinded electromyographic study and case reports. PATIENT SAMPLE:
      A previously reported group of 35 asymptomatic paid volunteers, ages 18 to 58
      years. Two elderly volunteers with moderate to severe spinal stenosis on magnetic
      resonance imaging (MRI), one significantly disabled, one asymptomatic. OUTCOME
      MEASURES: Blinded electromyographic testing, including MiniPM, a codified,
      quantified needle electromyography technique for the paraspinal muscles. In the
      two case reports, magnetic resonance imaging and 15-minute timed ambulation.
      METHODS: The 35 volunteers were tested by a blinded electromyographer using the
      MiniPM technique. The two older subjects underwent MRI, MiniPM and extensive
      electrodiagnostic evaluations, functional testing, complete history and physical
      examination. RESULTS: The patient with symptomatic stenosis had a MiniPM score of
      6 on each side, and the asymptomatic volunteer had a score of 0. In the
      asymptomatic subject group, reproducible evidence for denervation was found in 20
      subjects (57%), sparsely distributed, but more caudal than cranial (p<.0001).
      Based on conservative estimates of nerve regeneration rates, the population
      averaged a detected axonotemesis denervating event approximately once every 120
      days. CONCLUSIONS: Paraspinal denervation may be proven to be a better marker
      than MRI findings for symptomatic spinal stenosis. Subtle paraspinal muscle
      denervation occurs frequently in asymptomatic persons. Whether a cause or an
      effect, paraspinal denervation might lead to hypermobility and thus progression
      along the degenerative cascade.

PMID- 14589469
TI  - Extramedullary sarcoid lesion mimicking intraspinal tumor.
AB  - BACKGROUND CONTEXT: Spinal sarcoidosis is rare. Most spinal sarcoid lesions are
      intramedullary, and only three cases of extramedullary sarcoid lesions have been
      reported. PURPOSE: To describe a case of an extramedullary sarcoid lesion in a
      patient that did not have systemic involvement and to review the literature of
      spinal sarcoidosis. STUDY DESIGN/SETTING: Case report and review of the
      literature. PATIENT SAMPLE: Case report. OUTCOME MEASURES: Report of resolution
      of symptoms. METHODS/DESCRIPTION: The patient was a 33-year-old woman who had
      neck pain and pain radiating to the right scapula area and down the right arm
      into her hand and wrist. She also complained of numbness, tingling, muscle spasms
      and tremors, and had difficulty with writing. Magnetic resonance imaging showed a
      mass that was extramedullary in the right lateral aspect of the spinal canal at
      the level of C5 and extending into the right C5-6 neuroforamen. Admitting
      diagnosis of neurofibroma was made. The patient underwent C4, C5 and C6
      laminoplasty and gross total resection of an intradural extramedullary tumor. The
      lesion encroached on the neuroforamen on the right side involving the C6 nerve
      root, was grossly adherent to some of the rootlets and looked like a Schwannoma.
      Gross total resection of the tumor was performed. Pathological examination of the
      specimen showed a noncaseating granulomatosis consistent with sarcoid.
      Postoperative testing did not reveal systemic involvement of sarcoidosis. The
      patient was treated with corticosteroids. RESULTS: The patient made a
      satisfactory recovery, returned to work full-time, and had no complaints of
      neurological symptoms. CONCLUSIONS: An extramedullary sarcoid lesion is rare.
      Unlike intramedullary sarcoid lesions, it can be totally removed. If no systemic
      sarcoidosis is present, the patient can have a satisfactory recovery.

PMID- 14589470
TI  - Provocative discography in volunteer subjects with mild persistent low back pain.

PMID- 14589472
TI  - When is an outcome an outcome?

PMID- 14589473
TI  - The effect of a 5-day space flight on the immature rat spine.
AB  - BACKGROUND CONTEXT: Spaceflight has many reported effects upon the
      musculoskeletal system structure and function. This study was designed to
      determine the effect of a 5-day flight on the rat spine. METHODS: In September
      1991, 8 neonatal rats were flown aboard the Space Shuttle Columbia flight STS-48
      during a 5-day mission. Upon return to earth, the spines were dissected, frozen
      and shipped to our laboratory. Matched ground-based rats were used as controls.
      The spines were radiographed and then slowly thawed. Individual vertebrae were
      subjected to compressive biomechanical testing using an Instron tester (Instron
      Corp, Canton, MA, USA) and then processed for determination of calcium and
      phosphorus content. The intervertebral discs were placed in physiological saline
      and the stress-relaxation characteristics measured. The discs were then
      lyophilized and assayed for collagen and proteoglycan content. Disc height on
      radiographs was measured by image analysis. RESULTS: After space flight, the
      heights of the discs were found to be 150 to 200 microns greater, although the
      values were not statistically significant. There was no difference in the
      resiliency of the thoracic discs as determined by stress-relaxation. However, in
      the lumbar discs, space flight increased the resiliency (p<.01). There was no
      difference in water content. In both the thoracic and lumbar discs there was a
      3.3-fold increase in hydroxyproline-proteoglycan ratio after space flight.
      However, because of the small sample size, these values were not statistically
      significant. In the vertebrae, there was no difference in calcium-phosphate ratio
      or compressive strength. CONCLUSIONS: These data suggest that even after a short
      5-day flight, the spine begins to undergo biomechanical and biochemical changes.
      In addition, the weightless environment in space may provide a good model to
      study the effects of immobilization on earth.

PMID- 14589474
TI  - Characterization of a developing lumbar arthrodesis in a sheep model with
      quantitative instability.
AB  - BACKGROUND CONTEXT: Mechanical forces have been considered responsible for stress
      shielding an arthrodesis, but the biology of a developing lumbar fusion has not
      been well characterized. PURPOSE: A large animal model was used to test the
      hypothesis that mechanical forces modify the biological processes involved in a
      developing bony fusion. STUDY DESIGN: Lumbar fusion was performed in an ovine
      model using custom instrumentation that permitted a controlled degree of anterior
      posterior translation after surgery. Fusion sites were evaluated by radiography,
      microradiography, histology and histomorphometry at time points that corresponded
      with predicted early and later stages of bone healing. METHODS: Fourteen
      skeletally mature ewes underwent lumbar spinal fusion under general anesthesia.
      In the control (stable) group, the spine was rigidly fixed with a cage anteriorly
      and pedicle screws posteriorly. In the experimental (unstable) group, the spine
      was destabilized by an annulectomy (with no anterior implant) and custom pedicle
      screws that allowed 2 mm of anterior-posterior translation. Animals were
      euthanized 6 and 12 weeks after surgery. RESULTS: Radiographs confirmed that the
      fusion mass had not fully consolidated at either time point. Microradiographs
      revealed a trend toward increased bone formation at 6 weeks in the stable case as
      compared with the unstable, but by 12 weeks, this trend had reversed (p=.03).
      Intramembranous bone formation was the primary mechanism of healing near the
      transverse process in animals with both stable and unstable fixation. In the area
      between the two transverse processes, new bone formation occurred primarily
      through endochondral ossification. At 12 weeks, the stable case had significantly
      more cartilage formed (p=.023) but less newly formed bone (p=.07) as compared
      with the quantitatively unstable. CONCLUSIONS: This clinically realistic animal
      model allowed characterization of the biology of the developing arthrodesis
      before fusion. Under stable or unstable conditions, endochondral ossification was
      the predominant mechanism of new bone formation within the intertransverse
      process region. This finding, which contrasts with previous reports from small
      animal models of spine fusion, may reflect a difference in biology that results
      from the increased size of the intertransverse space in sheep as compared with
      small animals. Interestingly, mechanical instability increased the formation of
      new bone within this region, but not at the transverse process. Endochondral
      ossification therefore appears to respond to mechanical factors in the fusion
      site. The ovine model shows promise as an alternative to the rabbit model and may
      provide a more stringent test for potential new surgical and nonsurgical
      strategies for spine fusion.

PMID- 14589475
TI  - Greater trochanteric pain syndrome in patients referred to orthopedic spine
      specialists.
AB  - BACKGROUND CONTEXT: Greater trochanteric pain syndrome (GTPS) is a regional
      syndrome characterized by pain and reproducible tenderness in the region of the
      greater trochanter, buttock or lateral thigh that may mimic the symptoms of
      lumbar nerve root compression. Despite these known features, the diagnosis of
      GTPS is often missed, and documentation of its prevalence in an orthopedic spine
      specialty practice is lacking. PURPOSE: To determine the prevalence of the GTPS
      in patients referred to a tertiary care orthopedic spine referral center for the
      evaluation of low back pain, and to describe the demographic and clinical
      characteristics of patients with this syndrome. STUDY DESIGN/SETTING:
      Retrospective analysis. PATIENT SAMPLE: A total of 247 consecutive patients
      referred for low back pain from August 1998 through December 2000. OUTCOME
      MEASURES: Clinical response to injection, demographic characteristics, physical
      examination findings, prevalence of GTPS and preexisting diagnostic evaluations.
      METHODS: The diagnosis of GTPS was made based on history and physical examination
      and was confirmed by response to anesthetic corticosteroid injection. Demographic
      and clinical characteristics of the study group were evaluated. Follow-up data
      were available at a mean of 8 weeks postinjection (range, 2 to 48 weeks).
      RESULTS: The prevalence of GTPS was 20.2% (51 of 252). Mean age (54 years) was
      the same for patients with (range, 25 to 85 years) and without (range, 17 to 85
      years) GTPS. Significantly more women than men had GTPS (p<.03). Of the 51
      patients diagnosed with GTPS at initial presentation, 54.9% (28 of 51) had
      already obtained a magnetic resonance imaging examination (although only 15.7%,
      ie, 8 of 51, demonstrated objective neurologic findings) and 62.7% (32 of 51) had
      previously been evaluated by an orthopedist or neurosurgeon; one patient had
      undergone two lumbar decompressions without clinical improvement before our
      evaluation. CONCLUSIONS: GTPS accounts for a substantial proportion of patients
      referred to our center for evaluation of low back pain. Both primary care
      physicians and specialty surgeons may miss this diagnosis, most common in middle
      aged women. Accurate recognition of this problem earlier in the evaluation of
      patients with low back, buttock or lateral thigh symptoms may dramatically reduce
      costly patient referrals and diagnostic tests and may prevent unwarranted
      surgery.

PMID- 14589476
TI  - Evaluation of calcium sulfate paste for augmentation of lumbar pedicle screw
      pullout strength.
AB  - BACKGROUND CONTEXT: Many authors have evaluated the components responsible for
      ultimate pullout strength of pedicle screws. In these studies, one important
      variable has been the screw fixation. Because pedicle screw fixation has
      increased in popularity over recent years, so has the need for augmentation in
      difficult situations. Polymethylmethacrylate (PMMA) has been established as the
      gold standard in terms of strength of fixation but has the potential for severe
      complications when applied in spine surgery. Calcium sulfate is an alternative to
      PMMA, because it lacks the exothermic reaction, is potentially osteoconductive
      and is resorbed by the body in 30 to 60 days. PURPOSE: To determine the strength
      of a new calcium sulfate cement in terms of pedicle screw augmentation. The
      purpose was to evaluate calcium sulfate versus PMMA in terms of pullout strength.
      PMMA was considered the gold standard in terms of strength for this experiment.
      STUDY DESIGN: Lumbar vertebrae implanted with pedicle screws were subjected to
      axial pullout tests. The force required to cause implant failure was measured and
      compared for three methods of fixation. OUTCOME MEASURES: Force to failure
      (Newtons) for each pedicle test was recorded and analyzed with results from
      similarly augmented pedicles. METHODS: Lumbar vertebrae were harvested from four
      cadavers and implanted with pedicle screws. These screws were either placed in
      native bone or augmented with either calcium sulfate paste or PMMA. In those
      pedicles that had augmentation, the material was permitted to set for a minimum
      of 24 hours. Axial pullout tests were then performed using an MTS (Materials
      Testing System Corporation, Minneapolis, MN) testing machine. The screws were
      pulled out over a distance of up to 6 mm at 0.25 mm/sec. This rate and distance
      ensured failure in each case. The load to failure was recorded for each pedicle.
      RESULTS: Calcium sulfate augmentation improved pedicle screw pullout strength
      significantly when compared with native bone (p=.0003). This represented an
      average increase of 167% over the native bone. Likewise, PMMA improved the
      pullout strength significantly over native bone (p<.0001) for an average increase
      of 199%. There were no significant differences between the calcium sulfate and
      PMMA augmentation (p=.0791), although the PMMA averaged 119% of the strength of
      calcium sulfate. CONCLUSIONS: Although PMMA is considered the gold standard in
      terms of fixation strength, its use around the spine has been limited because of
      concern over complications. The calcium sulfate bone paste tested in this study
      demonstrated strength similar to PMMA without the major risks to the spinal cord.
      In addition, the calcium sulfate paste allows for possible osteoconduction to aid
      in spinal fusion. Further study is needed to determine the applicability of this
      calcium sulfate paste in the clinical setting of spine surgery.

PMID- 14589477
TI  - Assessment of a synthetic anterior cervical ligament in a spinal fusion model in
      sheep.
AB  - BACKGROUND CONTEXT: The anterior cervical ligament is routinely excised during
      cervical interbody fusion. Loss of this ligament may predispose to instability at
      the fusion site. Anterior plating restores stability but leads to a risk of
      stress shielding. An alternative approach would be to use a less rigid fixation
      system that would provide anterior support while allowing micromotion that could
      enhance bone healing within the fusion site. PURPOSE: To determine whether
      augmentation of an interbody fusion with a synthetic ligament enhances fusion.
      STUDY DESIGN: Prospective randomized study in a large animal model of cervical
      fusion. OUTCOME MEASURES: The primary outcome was evidence of interbody fusion,
      as determined by radiography, computed tomography (CT), histology and
      biomechanical testing. METHODS: Twelve skeletally mature sheep underwent single
      level (C2-3) anterior discectomy and interbody fusion using fresh frozen
      allograft. In six animals, the fusion was augmented with a braided polyethylene
      device rigidly fixed to C2 and C3 with screws. Sheep were euthanized 12 weeks
      postoperatively. Specimens were radiographed and then examined by CT. Six fusion
      sites (three control, three augmented) were used for nondestructive biomechanical
      testing to assess the stability of the fusion site. The remaining specimens were
      processed for undecalcified histology. RESULTS: As determined by radiography, the
      augmented group had 83% solid union as compared with 67% in the control group
      (p<.05). There was no difference regarding bone graft dislodgment between the two
      groups. The extension stiffness of the augmented group was significantly higher
      (p<.05) than that of controls, but there was no significant difference between
      the two groups in flexion stiffness. There was no significant difference in bone
      formation in the two groups as determined by CT and histology, although there was
      a trend for increased endochondral ossification in the augmented repairs. There
      was no evidence of significant adverse tissue reactions to the ligament.
      CONCLUSIONS: Use of a synthetic ligament was associated with a moderate increase
      in fusion rate and a statistically significant increase in fusion site stiffness
      in extension. The use of an augmentation device, such as this synthetic ligament,
      may be beneficial in cervical fusion, especially when multilevel surgery is being
      contemplated.

PMID- 14589478
TI  - Impact of functional restoration after anterior cervical fusion on chronic
      disability in work-related neck pain.
AB  - BACKGROUND CONTEXT: Spinal surgery in the workers compensation population shows
      evidence of less favorable outcomes than in general health cases. Although spine
      surgery has been alleged to be a cause of poor outcomes, such outcomes may be
      improved by appropriate postsurgical rehabilitation. PURPOSE: To compare
      objective demographic, physical and psychological measurements and socioeconomic
      outcomes of treatment in work-related disabling cervical pain for the combination
      of anterior cervical fusion (ACF) plus functional restoration, compared with
      rehabilitation alone. STUDY DESIGN/SETTING: A prospective study of patients
      undergoing ACF for degenerative disc disease before rehabilitation for work
      related musculoskeletal disorders versus neck pain unoperated controls, with data
      collected in an outpatient tertiary interdisciplinary rehabilitation setting.
      PATIENT SAMPLE: A group of 52 patients completed a functional restoration
      treatment program after undergoing ACF (Group S) at one or two levels for
      degenerative cervical disc disease. During the study period, 625 patients with
      work-related neck pain were identified from the same study population, from which
      a rehabilitation (Group R) comparison group (n=150) was identified who were
      stratified according to the number and location of other compensable body parts.
      OUTCOME MEASURES: Socioeconomic outcomes relevant to chronic disabling work
      related cervical spinal disorders are reported based on 1-year posttreatment
      interviews. Pre- to posttreatment assessment of pain intensity, disability,
      depression and cumulative physical capability were assessed prospectively.
      METHODS: All patients were totally or partially disabled before completing an
      intensive, medically supervised, functional restoration program combining
      quantitatively directed exercise progression with a multimodal disability
      management approach. Preprogram preparation included drug detoxification,
      psychotropic medication management and preparatory aerobic and mobility training.
      The intensive treatment phase involved strength and endurance training, with
      counseling geared to goals of work return and fitness maintenance. The 1-year
      structured clinical interview had a contact rate of 93% to 95%, and partial
      information acquisition on all patients. RESULTS: Although Group S had lower work
      return and work retention outcomes, the differences were not significant. Group S
      patients had significantly more health utilization from a new provider in the
      year after completion of functional restoration (46% vs 24%; OR=2.7 [1.3, 5.3],
      p<.004). Group S patients were also more likely to be depressed, both at pre- and
      postrehabilitation. There were no significant differences in recurrent injury,
      additional surgery, physical measures or pain/disability self-report between the
      groups. CONCLUSIONS: Workers compensation patients with chronic disabling work
      related cervical spinal disorders who undergo a cervical fusion, combined with
      functional restoration, have socioeconomic outcomes after their surgery
      statistically similar to those for unoperated controls. Surgery patients had a
      higher rate of additional health-care-seeking behaviors from new providers and a
      greater likelihood of being clinically depressed before and after rehabilitation.
      This study suggests that cervical fusion for degenerative disc disease in workers
      compensation patients is not contraindicated, as long as interdisciplinary
      rehabilitation is available for complex cases after the surgical procedure.

PMID- 14589479
TI  - Clinical experience with intrathecal bupivacaine in combination with opioid for
      the treatment of chronic pain related to failed back surgery syndrome and
      metastatic cancer pain of the spine.
AB  - BACKGROUND CONTEXT: Bupivacaine is a local anesthetic agent of the amide class.
      This drug has been used in many clinical situations including intrathecal
      infusion. The literature regarding intrathecal bupivacaine is limited to small
      case studies, and anecdotal reports. This article examines a large patient group
      receiving bupivacaine with opioids over an extended period of time and analyzes
      efficacy and safety. The patients had pain related to failed back surgery
      syndrome or metastatic cancer to the spine. PURPOSE: The purpose of this study
      was to determine the efficacy and safety of intrathecal bupivacaine combined with
      opioids for treatment of pain of spinal origin when opioids alone were
      inadequate. The secondary purpose of this study was to determine if the
      combination of bupivacaine and opioids created a neurological safety risk. STUDY
      DESIGN/SETTING: The study design was retrospective, and involved consecutive
      medical records review by a disinterested third party. PATIENT SAMPLE: One
      hundred nine consecutive patients were studied for a total of 6,780 patient weeks
      of bupivacaine/opioid infusion. These data were compared with a comparable time
      in the opioid alone treatment arm. The population included 84 noncancer patients
      and 25 cancer patients. OUTCOME MEASURES: The primary outcome measure was pain
      relief obtained by a group of patients with a combination of bupivacaine and
      opioids as compared with opioid alone when delivered by intrathecal infusion. The
      visual analog scale was used to measure pain levels. Secondary objectives
      included measuring the amount of oral and transdermal medication required (opioid
      and nonopioid), emergency visits, routine office visits and patient satisfaction.
      These secondary objectives give a measure of health-care utilization. We also
      reviewed neurological complications during the combined arm of treatment.
      METHODS: The study was done retrospectively with 109 consecutive patients.
      Patient chart reviews were used to determine the visual analog scales, amount of
      oral opioids, oral nonopioid adjuvant and patient satisfaction ratings. Patient
      satisfaction and pain rating was measured by a visual analog scale. Other factors
      recorded were emergency room visits, doctor's visits (other than the primary pain
      physician) and pain center visits. We also reviewed records for neurological
      deficits in the opioid arm and the combined arm. The t test was used to analyze
      statistical significance. RESULTS: The findings suggested that in the combination
      arm the pain relief was significantly better (p=.008), the number of oral opioids
      used were significantly less (p=.008), the number of oral nonopioid adjuvants
      were reduced, the number of doctor's visits were less in the combined arm
      (p=.008), the number of pain clinic visits were less (p=.03), the number of
      emergency visits were significantly less (p=.01) and patient satisfaction was
      better (p=.003). The total dose of morphine was reduced by 23% in the combined
      arm (p=.005). During the course of treatment with intrathecal bupivacaine, there
      were no irreversible complications. CONCLUSION: Bupivacaine, when used in
      combination with opioids, is a helpful and safe method of treatment in a select
      population of patients who have not responded to intrathecal opioids alone.

PMID- 14589481
TI  - Medication-assisted spinal manipulation.
AB  - BACKGROUND CONTEXT: The acceptance of spinal manipulation as a reasonable method
      of treating certain patients with spinal pain over the past decade has led to a
      renewed interest and increased use of these techniques performed in conjunction
      with commonly used medications and procedures. Manual therapy is increasingly
      being used in conjunction with anesthetics, sedatives or analgesics as well as
      local, epidural and intra-articular injections. PURPOSE: This report provides a
      review of the literature and presents a description of current clinical practice
      methods for the application of the different techniques of medication-assisted
      spinal manipulation therapy followed by a discussion of the current clinical
      support and the published indications, contraindications and complications for
      each of these procedures. STUDY DESIGN/SETTING: This technical report integrates
      a literature review with information gathered through personal interviews, review
      of medicine-assisted manipulation courses and observations of clinical
      procedures. METHODS: A PubMed search from 1966 to the present was performed to
      identify appropriate articles concerning the combination of spinal manipulation
      therapy with such medical procedures as the use of anesthetic, conscious
      sedation, local injection of analgesic, anti-inflammatory and proliferant agents
      and intra-articular injections. Additional articles and information were gathered
      through review of pertinent references, attendance of various technique specific
      seminars and communication with experts familiar with these procedures. RESULTS:
      Four categories of medication-assisted manipulation were identified: manipulation
      under general anesthesia or sedation, manipulation under epidural anesthesia with
      or without epidural steroid injection, manipulation under joint
      anesthesia/analgesia, and manipulation with injectants, such as steroids or
      proliferant agents. The literature consists primarily of case reports and case
      series with two randomized controlled trials and one cohort study. CONCLUSIONS:
      Medicine-assisted spinal manipulation therapies have a relatively long history of
      clinical use and have been reported in the literature for over 70 years. However,
      evidence for the effectiveness of these protocols remains largely anecdotal,
      based on case series mimicking many other surgical and conservative approaches
      for the treatment of chronic pain syndromes of musculoskeletal origin. There is,
      however, sufficient theoretical basis and positive results from case series to
      warrant further controlled trials on these techniques.

PMID- 14589480
TI  - Management of postprocedural discitis.
AB  - BACKGROUND CONTEXT: Fortunately, the incidence of postprocedural discitis is
      relatively uncommon. The paucity of physical examination findings behooves the
      spine care practitioner to have a high index of suspicion in any patient
      presenting with increasing back pain after an invasive spinal procedure. The
      diagnosis can often be established in a timely fashion based on the history,
      physical examination, laboratory studies (erythrocyte sedimentation rate, C
      reactive protein and blood cultures) and imaging studies (plain radiographs,
      magnetic resonance imaging, computed tomography and radionuclide scanning).
      PURPOSE: To review the English literature on the subject of postprocedural
      discitis. The incidence, pathophysiology, laboratory markers and imaging findings
      are discussed. Recommendations on treatment strategies are presented along with
      long-term clinical outcomes of this postprocedure complication. METHODS: A
      contemporary English literature search of MEDLINE and PubMed on the topic of
      postoperative discitis was performed. RESULTS: The incidence of postprocedural
      discitis is approximately 0.2%. The most common etiologic agent is Staphylococcus
      aureus. The C-reactive protein is the most sensitive clinical laboratory marker
      to assess the presence of infection and effectiveness of treatment response.
      Magnetic resonance imaging is the imaging modality of choice in the diagnosis of
      spinal infection. The majority of patients are managed adequately with organism
      specific antibiotics and spinal immobilization with good long-term outcomes.
      Operative intervention (open biopsy followed by antibiotic treatment and spinal
      immobilization or debridement and reconstruction) in patients who fail to respond
      to nonoperative treatment or in the presence of neurologic worsening has been
      demonstrated. CONCLUSION: Postprocedural discitis is a rare complication after
      any invasive spinal procedure. It is imperative for the treating surgeon to
      maintain a high index of suspicion. Appropriate laboratory and imaging studies
      are invaluable in establishing a timely diagnosis. In the majority of patients,
      antibiotic treatment along with spinal immobilization has been shown to produce
      good long-term outcomes. Operative intervention is rarely necessary in patients
      failing conservative treatment.

PMID- 14589482
TI  - Lumbar isthmic defects in teenagers resulting from stress fractures.
AB  - BACKGROUND CONTEXT: An accepted classification of spondylolysis exists. However,
      etiology remains controversial. There are several reports supporting acquired
      stress fractures in the etiology of this condition, although radiographic
      evidence of an acquired fracture in a given individual is very rare. PURPOSE: To
      present evidence of development of pars defects during the teenage years. STUDY
      DESIGN/SETTING: Retrospective review of charts. PATIENT SAMPLE: Two case studies.
      METHODS: Charts and X-rays were reviewed to look for radiographic evidence of
      development of pars defects in patients who were ultimately found to have
      spondylolisthesis or spondylolysis. RESULTS: Two cases were found that
      demonstrated development of a pars fracture. Both patients had radiographic
      evidence that these fractures developed during their teenage years. Both were
      active individuals with a consistent level of participation in athletics.
      CONCLUSIONS: Although development of pars defects may be multifactorial, these
      two cases support the concept that these fractures can be acquired lesions
      resulting from repetitive stress injury. They also demonstrate that isthmic
      defects can arise in teenagers, in these cases in an athletic population.

PMID- 14589486
TI  - To be taken seriously, proofread the articles.

PMID- 14589488
TI  - Words, meaning and communication in spine care.

PMID- 14589489
TI  - Quantifying risk of transfusion in children undergoing spine surgery.
AB  - BACKGROUND CONTEXT: The risks and costs of transfusion are a great concern in the
      area of pediatric spine surgery, because it is a blood-intensive procedure with a
      high risk for transfusion. Therefore, determining the predictors of transfusion
      in this patient population is an important first step and has the potential to
      improve upon the current approaches to reducing transfusion rates. In this study,
      we reveal several predictors of transfusion in a pediatric patient population
      undergoing spine surgery. In turn, we present a general rule of thumb ("rule of
      two's") for gauging transfusion risk, thus enhancing the surgeon's approach to
      avoiding transfusion in certain clinical scenarios. PURPOSE: This study was
      conducted to determine the main factors of transfusion in a population of
      pediatric patients undergoing scoliosis surgery. The goal was to present an
      algorithm for quantifying the true risk of transfusion for various patient groups
      that would highlight patients "at high risk" for transfusion. This is especially
      important in light of the various risks associated with undergoing a transfusion,
      as well as the costs involved in maintaining and disposing of exogenous blood
      materials. STUDY DESIGN/SETTING: This is a retrospective review of a group of
      children who underwent scoliosis surgery between 1988 and 1995 at an academic
      institution. PATIENT SAMPLE: A total of 290 patients were analyzed in this study,
      of which 63 were transfused and 227 were not. OUTCOME MEASURES: No outcomes
      measures were used in this study. METHODS: A retrospective review of 290 patients
      presenting to our institution for scoliosis surgery was conducted, with a focus
      on socioclinical data related to transfusion risk. Univariate analysis and
      logistic regression were used to quantify the determinants of transfusion risk.
      RESULTS: Univariate analysis identified many factors that were associated with
      the risk of transfusion. However, it is clear that several of these factors are
      dependent on each other, obscuring the true issues driving transfusion need. We
      used multivariate analysis to control for the various univariate predictors of
      transfusion. Our logistic regression model suggested that the type of scoliosis
      (odds ratio [OR], 2.02; 95% confidence interval [CI], 1.07 to 3.82), degree of
      curvature (OR, 1.012/degree curve; 95% CI, 1.01 to 1.03), and use of
      erythropoietin (OR, 0.29; 95% CI, 0.14 to 0.62) were the main determinants of
      transfusion risk for our population. CONCLUSIONS: The main risk factors of
      transfusion were used to formulate a simple algorithm, which can be used to
      quantify transfusion risk and to guide efforts to avoid transfusion in children
      undergoing spinal surgery. Given a 10% baseline risk for transfusion, our "rule
      of two's" indicates that each risk factor approximately doubles the chance of
      transfusion, whereas the administration of recombinant human erythropoietin
      roughly halves the risk of transfusion.

PMID- 14589490
TI  - The effect of osteogenic protein-1 in instrumented and noninstrumented
      posterolateral fusion in rabbits.
AB  - BACKGROUND CONTEXT: The use of rigid instrumentation combined with bone graft
      makes intuitive sense given the requirements for vascular ingrowth, bone
      formation and a stable environment for the cellular events of healing to develop.
      However, with the advances of potent osteoinductive growth factors, the role of
      internal fixation may come into question. Whether bone morphogenic proteins
      (BMPs) would benefit from a more "stable" spinal segment for bone production and
      modeling remains unknown. In addition, it is unknown whether BMP and rigid
      fixation may have an additive effect on fusion healing. PURPOSE: This study is
      proposed to test the hypothesis that rigid fixation in the lumbar spine would be
      advantageous to achieve fusion for autogenous bone grafting, but fusion would
      occur regardless of fixation with the use of osteogenic protein (OP)-1. STUDY
      DESIGN/SETTING: A histologic and radiographic analysis of BMP in a rabbit lumbar
      fusion model. METHODS: Thirty-two rabbits were randomized into four groups: 1)
      control animals: in situ posterolateral L5-L6 arthrodesis using autogenous iliac
      crest bone graft; 2) fixation group: posterolateral arthrodesis L5-L6 with
      autogenous bone graft and interspinous fixation; 3) OP-1 group: in situ
      posterolateral L5-L6 arthrodesis using OP-1 and 4) combined OP-1 and fixation
      group. Radiographic fusion analysis was performed with computed tomography scans
      at 3 and 12 weeks after surgery. Decalcified histology was performed to assess
      tissue morphology and cellularity. RESULTS: Minimal evidence of fusion was noted
      at 3 weeks with autograft or OP-1. By 12 weeks, all OP-1-treated animals had
      solid fusion, whereas no fusion was noted in autograft animals. The addition of
      fixation slightly increased radiographic fusion at 3 weeks in autograft and OP-1
      groups but did not affect OP-1 animals at 12 weeks where all were fused.
      Decalcified histologic results confirmed the proliferative bone formation noted
      with OP-1 and the variable cellular response with autograft. CONCLUSIONS: The
      results of the present study suggest that the osteoinductive effect of OP-1 may
      be only minimally enhanced early in the bone healing process but does not appear
      to be affected in the long term by spinal fixation in the rabbit intertransverse
      fusion model. Fixation appeared to enhance early fusion in the autograft group.

PMID- 14589491
TI  - Anterior cervical corpectomy and strut graft fusion using a different method.
AB  - BACKGROUND CONTEXT: Strut graft fusion after corpectomy is frequently indicated
      for certain pathologies in the cervical spine. The "key-hole" technique and "dove
      tail" technique are the popular methods used to insert the strut graft at
      present. Segmental collapse secondary to seating of the graft on cancellous bone
      and cord injury from placement or dislodgement the graft are our concerns. Our
      method was designed to solve these possible problems without affecting the
      arthrodesis. PURPOSE: To evaluate the results of this method that allows the
      graft to seat on both the hard end plate and cancellous bone of the upper and
      lower contacting vertebrae in a easy and safe way after varying levels of
      corpectomy in the cervical spine. STUDY DESIGN: A retrospective clinical and
      radiographic study conducted by an independent observer was performed on 23
      patients treated with this different strut grafting method after cervical
      corpectomy, with at least 2 years of follow-up. PATIENT SAMPLE: A total of 23
      patients from 1983 to 1994 underwent fusion using our strut grafting method with
      fibular allograft packed with autogenous bone. No augmented internal
      instrumentation was used in all these patients. The patients with an incomplete
      record or less than 2 years of follow-up were excluded beforehand. OUTCOME
      MEASURES: Clinical outcome was assessed by a score based on three factors: neck
      pain, dependence on medicine and ability to return to work. The total score of
      these factors was seven. A score from 0 to 3 was defined as satisfactory, and a
      score from 4 to 7 was defined as unsatisfactory. The result of graft fusion,
      collapse of interbody height and loss of lordotic angle corrected by the graft
      were evaluated through the radiographic studies. METHODS: The operative technique
      creates a notch in the anterior cortex and end plate of the respective superior
      and inferior vertebraes. Cylinder allograft filled with autogenous cancellous
      bone was used as bone graft for all patients. The bone graft is cut with
      corresponding pegs at both ends. The graft is inserted into the corpectomy space
      with the pegs inserted into the notches and the remainder of the graft placed
      onto the preserved superior and inferior bony end plates. RESULTS: Twenty
      patients achieved successful fusion (87%). On average, the loss of anterior and
      posterior interbody height was 2.79 mm and 2.93 mm, respectively. The average
      loss of lordotic correction was 2.83 degrees. Eighty-three percent achieved
      satisfactory clinical outcomes. There were no neurologic injuries encountered
      during the operation. Partial graft dislodgment occurred in two patients (8.7%).
      CONCLUSIONS: This different method of strut grafting after cervical corpectomy
      has proven its safety and efficacy in its fusion and clinical results.

PMID- 14589492
TI  - A pilot study to evaluate the effectiveness of small intestinal submucosa used to
      repair spinal ligaments in the goat.
AB  - BACKGROUND CONTEXT: Destabilization of the lumbar spine results from sacrifice of
      the anterior longitudinal ligament and disc when removed for graft or cage
      placement. In a similar fashion, transection of the interspinous ligament during
      surgical approaches to the posterior spine may result in segmental instability.
      Such instability can cause abnormal motion or implant migration resulting in a
      higher incidence of pseudarthrosis. Small intestinal submucosa (SIS) is a
      naturally occurring extracellular collagen-based matrix, which is derived from
      porcine small intestine. SIS contains cytokines and growth factors and has been
      shown to act as a resorbable scaffold in vivo that promotes host soft tissue
      regeneration with little scar tissue formation. SIS can be manufactured in
      laminated sheets of various sizes and thicknesses for different indications.
      Successful applications of SIS in animals have included dural substitution,
      rotator cuff repair, vessel repair, abdominal and bladder wall repair, and
      others. However, SIS has not been investigated to determine its ability to
      facilitate regeneration of spinal ligaments. PURPOSE: The purpose of this pilot
      study was to evaluate the efficacy of SIS as a barrier to prevent interbody
      device migration, and to act as a scaffold for regeneration of the anterior
      longitudinal ligament (ALL) and posterior interspinous ligament (PISL) in a goat
      model. STUDY DESIGN/SETTING: The thoracolumbar spine of the goat was exposed
      surgically. After resection and removal of the ALL or PISL at alternating levels,
      either SIS was placed or no treatment was administered. New ligament formation
      and SIS resorption were monitored over a 12-week period. OUTCOME MEASURES: Plain
      film radiographs and histomorphometry were used to assess the progress of healing
      over a 12-week time period. METHODS: Four skeletally mature nubian-alpine
      crossbred goats were used in this study. Under general anesthesia, each T10 to L5
      motion segment was exposed surgically. Both anterolateral and posterior
      approaches were performed simultaneously at each level. Anteriorly, alternating
      levels received either 1) anterior discectomy, sacrifice of ALL and placement of
      SIS (SIS group); 2) anterior discectomy, sacrifice of ALL and no SIS (surgical
      control group) or 3) no surgical intervention (nonoperative group). A solid
      interbody spacer was placed into the disc space after discectomy to deter
      spontaneous anterior interbody fusion. Posteriorly, alternating levels were
      treated with either 1) sacrifice of the PISL with placement of SIS (SIS group);
      2) sacrifice of PISL and no SIS (surgical control group) or 3) no surgical
      intervention (nonoperative group). The SIS was secured to the adjacent superior
      and inferior spinous processes to create a tension-band effect. Animals were
      radiographed immediately postoperatively to confirm placement of interbody
      spacers and anchors and to serve as a baseline for monitoring interbody spacer
      positioning. After surgery, all animals were allowed unrestricted motion for 12
      weeks. At the end of the 12-week period, animals were radiographed and
      euthanized. The lumbar spine was harvested en bloc and processed for decalcified
      histologic evaluation. The dorsal and ventral aspects of each motion segment were
      analyzed for signs of inflammation and scar tissue formation, residual SIS and
      regenerated ALL or PISL. RESULTS: All animals tolerated the surgical procedure
      well, and there were no intraoperative or anesthesia-related complications.
      Twelve-week radiographs showed some evidence of ventral migration of the
      interbody spacers in several animals. Fifty percent (two of four) of spacers in
      surgical control group levels had migrated more than 10 mm (resulting in complete
      migration out of the disc space), whereas no spacers migrated completely out of
      levels with SIS placed. Gross analysis at necropsy indicated iatrogenic scar
      formation at operated levels, the degree of which was not different from surgical
      control group to SIS levels. Histologic evaluation of areas where the ALL had
      been removed indicated formation of organized fibrilar collagenous tissue that
      spanned the disc space at some levels where the SIS was placed. In some cases,
      the newly formed tissue was approximately the thickness of the ALL at the
      nonoperative group levels. The newly formed collagenous tissue was accompanied by
      sparse focal areas of inflammation, with small fragments of residual SIS at some
      levels. At surgical control group levels, there was a varying degree of
      connective tissue that ranged from moderately organized to randomly oriented with
      no significant signs of inflammation. Similarly, histologic analysis of some
      levels where SIS was placed posteriorly showed formation of organized collagenous
      tissues where the PISL had been removed. CONCLUSIONS: In this model, the SIS
      patch was sufficient to prevent acute ventral migration of interbody spacers from
      the disc space. The extent of long-term healing and new tissue formation in the
      SIS group indicates that it may be efficacious as a reparative intervention for
      transected ligaments in the spine. Most SIS specimens showed formation of
      organized collagenous tissue, indicating a long-term potential for ligament
      formation. However, in this model, 12 weeks of postoperative healing is
      insufficient to assess the full potential of SIS as a spinal ligament repair.
      Further research that follows the healing process to a longer time point
      postoperatively may be necessary to fully understand the potential of SIS as a
      resorbable scaffold for tissue replacement.

PMID- 14589493
TI  - One- and two-level anterior cervical discectomy and fusion: the effect of plate
      fixation.
AB  - BACKGROUND CONTEXT: The success of arthrodesis for anterior cervical fusion
      depends on several factors, including the number of surgical levels. Internal
      fixation putatively improves the arthrodesis rate and outcome. PURPOSE: To
      provide medium-term follow-up data on the surgical success and patient outcome of
      one- and two-level anterior cervical discectomies and fusions and to determine
      the effect that plate fixation has on results. STUDY DESIGN: A prospective study
      of 40 patients who underwent modified Smith-Robinson anterior cervical discectomy
      and fusion at one or two operative levels. PATIENT SAMPLE: Forty patients.
      OUTCOME MEASURES: Odom criteria, Nurick grading system, radiographs. METHODS:
      Forty patients, with an average age of 44 years (range, 27 to 82), were followed
      for an average of 51 months (range, 24 to 85). All had an anterior discectomy,
      burring of the end plates and placement of an autogenous tricortical iliac crest
      graft at one (20 patients) or two levels (20 patients). Twenty-three were
      stabilized with the Cervical Spine Locking Plate (Synthes Spine, Paoli, PA), 4
      single level, 19 two level. All patients had follow-up office visits with
      examinations and radiographs. Radiographic union, postoperative pain relief and
      neurologic recovery were evaluated. RESULTS: Successful arthrodesis of single
      level procedures occurred in 11 of 16 unplated and 2 of 4 plated fusions. Primary
      bony union in the two-level group was achieved in 15 of 19 plated patients and
      did not occur in the single unplated procedure. Clinically, there were 12
      excellent, 5 good, 3 satisfactory and 0 poor outcomes among the single-level
      procedures. Among the dual-level procedures, there were 10 excellent, 5 good, 3
      satisfactory and 2 poor results. Nine of 16 who developed adjacent-level
      degeneration had pain. Five of the 9 also had nonunions. Of the 40, 3 had fibrous
      union at final follow-up, and 10 had revision surgery. CONCLUSIONS: The Cervical
      Spine Locking Plate improved the outcome of two-level procedures to that of
      uninstrumented one-level fusions. Adjacent-level degeneration is associated with
      persistent pain, especially if there is also a nonunion. Primary bony union is
      paralleled by a better clinical outcome.

PMID- 14589494
TI  - Osteoporosis testing in orthopedic practice.
AB  - BACKGROUND CONTEXT: Osteoporosis affects 75 million people in the United States,
      Japan and Europe. PURPOSE: The purpose of this article is to review the severity
      of the problem of osteoporosis and thereby report the need for responsibility of
      today's spine orthopedic surgeons to recognize those at risk for osteoporosis,
      order diagnostic studies and treat patients' appropriately. STUDY DESIGN/SETTING:
      A spine specialty clinic took a sample of 325 different patients who had a bone
      mass densiometer (BMD) test to look at what percent of patients were
      osteoporotic. RESULTS: Twenty-one and a half percent of the patients tested
      positive for osteoporosis. CONCLUSION: There are millions of people with
      osteoporosis in the world's clinics. As the population ages, we will see a
      dramatic increase in the incidence of this disease unless appropriate
      intervention is undertaken. Osteoporosis is preventable and treatable.

PMID- 14589495
TI  - Bone grafting alternatives in spinal surgery.
AB  - BACKGROUND CONTEXT: Bone grafting is used to augment bone healing and provide
      stability after spinal surgery. Autologous bone graft is limited in quantity and
      unfortunately associated with increased surgical time and donor-site morbidity.
      Alternatives to bone grafting in spinal surgery include the use of allografts,
      osteoinductive growth factors such as bone morphogenetic proteins and various
      synthetic osteoconductive carriers. PURPOSE: Recent research has provided insight
      into methods that may modulate the bone healing process at the cellular level in
      addition to reversing the effects of symptomatic disc degeneration, which is a
      potentially disabling condition, managed frequently with various fusion
      procedures. With many adjuncts and alternatives available for use in spinal
      surgery, a concise review of the current bone grafting alternatives in spinal
      surgery is necessary. STUDY DESIGN/SETTING: A systematic review of the
      contemporary English literature on bone grafting in spinal surgery, including
      abstract information presented at national meetings. METHODS: Bone grafting
      alternatives were reviewed as to their efficacy in extending or replacing
      autologous bone graft sources in spinal applications. RESULTS: Alternatives to
      autologous bone graft include allograft bone, demineralized bone matrix,
      recombinant growth factors and synthetic implants. Each of these alternatives
      could possibly be combined with autologous bone marrow or various growth factors.
      Although none of the presently available substitutes provides all three of the
      fundamental properties of autograft bone (osteogenicity, osteoconductivity and
      osteoinductivity), there are a number of situations in which they have proven
      clinically useful. CONCLUSIONS: Alternatives to autogenous bone grafting find
      their greatest appeal when autograft bone is limited in supply or when acceptable
      rates of fusion may be achieved with these substitutes (or extenders) despite the
      absence of one or more of the properties of autologous bone graft. In these
      clinical situations, the morbidity of autograft harvest is reasonably avoided.
      Future research may discover that combinations of materials may cumulatively
      result in the expression of osteogenesis, osteoinductivity and osteoconductivity
      found in autogenous sources.

PMID- 14589496
TI  - Mini-open approach to the spine for anterior lumbar interbody fusion: description
      of the procedure, results and complications.
AB  - BACKGROUND CONTEXT: Since the introduction of threaded devices in the mid-1990s,
      anterior lumbar interbody fusion (ALIF) has become a staple in the armamentarium
      of the spine surgeon. The procedure, however, is heavily dependent on the ability
      of the approach surgeon to provide exposure quickly and safely in view of a
      reported incidence of vascular injury as high as 15% and 2.3% incidence of
      retrograde ejaculation. PURPOSE: This study describes a mini-open approach to the
      lumbar spine and discusses the results and the complications seen. STUDY
      DESIGN/SETTING: The study was designed to evaluate patients for possible
      complications of the approach while they were in the hospital undergoing ALIF.
      They were also followed for 6 months after the operation. PATIENT SAMPLE: A total
      of 686 approaches to the lumbar spine performed on 684 patients between August
      1997 and December 2000 were reviewed concurrently and retrospectively. OUTCOME
      MEASURES: All complications of the approach were reported. These included
      vascular injury, retrograde ejaculation, deep vein thrombosis (DVT), pulmonary
      emboli, infection, wound disruption/hernia, ileus, hematoma, myocardial
      infarction, stroke, peripheral ischemia, rectus muscle paralysis, aborted cases
      and death. METHODS: The patients were observed in the perioperative period and
      for 6 months postoperatively to determine the occurrence of complications related
      to the approach. The data collected included age, weight, gender, levels
      approached, time of completion of the approach, size of incision and
      complications. RESULTS: There were six arterial injuries (0.8%), six venous
      injuries (0.8%) and one instance of retrograde ejaculation (0.1%). In addition,
      there were seven cases that developed DVT (two ileofemoral and five calf
      popliteal, 1.0%), four cases of ileus lasting more than 3 days (0.6%), three
      wound infections above the fascia (0.4%), two hernias and two compartment
      syndromes. There was one myocardial infarction and one death. No rectus muscle
      paralysis occurred. CONCLUSIONS: This experience suggests that a well-planned
      small incision that preserves the musculature can be performed quickly and safely
      to allow the spine surgeon adequate access to the anterior lumbar spine. The
      learning curve, however, can be high even for experienced surgeons.

PMID- 14589501
TI  - A comment regarding the conclusion reached.

PMID- 14589502
TI  - Archives of Clinical Neuropsychology is the official publication of the National
      Academy of Neuropsychologists.

PMID- 14589497
TI  - Atypical lumbar disc herniation: a case report.
AB  - BACKGROUND CONTEXT: This is a case report of a right posterolateral L5-S1 disc
      herniation that migrated to the left cephalad level to impinge on the left L5
      nerve root as it exited the dura. The resultant free fragment migration is a rare
      variation of a posterolateral disc disruption. PURPOSE: The purpose is to report
      a rare variation of lumbar disc herniation not previously reported in the
      literature. STUDY DESIGN/SETTING: Case report. PATIENT SAMPLE: A 60-year-old
      white woman. OUTCOME MEASURES: Resolution of the patient's left lower extremity
      symptoms. METHODS: Not applicable. RESULTS: The patient experienced resolution of
      most of her left lower extremity symptoms after a slightly modified
      microscopically assisted lumbar hemilaminectomy, discectomy and nerve root
      decompression. CONCLUSIONS: This is a rare right to left migration of a
      sequestrated disc herniation, which was effectively treated with surgery.

PMID- 14589503
TI  - The practice of clinical neuropsychology in the United States.
AB  - This paper reports the results of a survey of current members of the American
      Psychological Association's Division of Clinical Neuropsychology and the National
      Academy of Neuropsychologists on issues regarding practice. Data were compared
      between groups and to the findings of two 1980 surveys. Specifically, respondents
      were asked to include their employment setting, source and scope of practice,
      assessment batteries, typical fees, background training, and extent of practice
      outside traditional neuropsychological domains. In general, it seems that in the
      interim 5 years, clinical neuropsychology has experienced a shift in primary work
      settings. In addition, members of different professional organizations reflect
      similar types of response patterns to the survey, irrespective of other factors.

PMID- 14589504
TI  - Cognitive profiles of some subtypes of learning disabled adults.
AB  - Test profiles of 100 learning disabled adults were analyzed in an attempt to
      determine if patterns of learning disability subtypes which have been identified
      in children also persist into adulthood. On the basis of Wide Range Achievement
      Test reading and arithmetic grade level scores, subjects were classified into one
      of three subgroups. The classification resulted in finding 32 subjects who were
      substantially better at reading than arithmetic, 17 who were better at arithmetic
      than reading, and the remaining 51 with less than a 1.5-year grade level
      discrepancy between reading and arithmetic. Subgroup membership was used as the
      independent variable in a series of one-way analyses of variance which tested for
      differences in performance patterns on the Wechsler Adult Intelligence Scale and
      components of the Halstead-Reitan Neuropsychological Test Battery. While results
      support the view that most learning disabled individuals do not have specific
      disabilities, results suggest that it is possible to identify relatively small
      specific subtypes similar to those previously identified in learning disabled
      children, with some doing well at reading but poorly at arithmetic, and others
      doing very poorly at reading but relatively better, but not normally, at
      arithmetic. Cognitive testing of the first of these two specific subtypes
      revealed particular deficits in visual-spatial, nonverbal problem solving and
      complex psychomotor tasks. The second subtype did better on tasks of that type,
      but poorly on linguistic tasks.

PMID- 14589505
TI  - Neuropsychological signs of asymptomatic carotid stenosis.
AB  - Several investigators have reported cognitive deficits associated with
      symptomatic carotid artery disease. This paper reports the findings of a study
      investigating cognitive deficits associated with asymptomatic carotid stenosis.
      Experimental subjects consisted of six patients who, in the course of routine
      physical examinations, showed carotid bruits and, on carotid ultrasound studies,
      showed 70% or greater stenosis in one or both arteries. No clinical symptoms had
      been associated with that stenosis. Six control subjects who were group-matched
      in terms of age and years of education were drawn from a control group evaluated
      previously for comparison with a transient ischemic attack (TIA) sample. All
      patients received a battery of tests consisting of a Wechsler Adult Intelligence
      Scale-Revised, abbreviated Halstead-Reitan Neuropsychological Battery, Revised
      Wechsler Memory Scale, and a written word fluency measure. Findings were
      converted to Rating Equivalents according to standard guidelines and an average
      Impairment Index was computed for each subject. ANOVA revealed that the two
      groups were significantly different in terms of the average Impairment Index. The
      clinical significance of these findings is discussed and implications for future
      research are reviewed.

PMID- 14589508
TI  - Verbal memory tests in the differential diagnosis of depression and dementia:
      discriminative power of seven test variations.
AB  - The many tasks for the assessment of verbal memory differ widely in features of
      presentation and retrieval. In this study, seven common memory tasks (immediate
      and delayed free recall, randomized presentation, selective reminding, serial
      recall, recognition after short and long delay) were compared for their
      discriminative power between depressed, demented, and healthy elderly subjects.
      Tasks that require little cognitive capacity were hypothesized to be particularly
      useful to differentiate the patient groups. Demented and depressed patients
      demonstrated deficits on all tests, the demented being more severe. Only
      recognition after long and short delay, and delayed recall distinguished demented
      from depressed patients. Delayed retrieval tasks were more useful to discriminate
      patient groups than tasks that require little cognitive capacity.

PMID- 14589509
TI  - Modal profiles for the Luria-Nebraska Neuropsychological Battery.
AB  - Modal Profile Analysis was used to cluster subjects on the clinical scales of the
      Luria-Nebraska Neuropsychological Battery, Form I (LNNB). The analysis produced
      22 modal profile types, of which seven were replicated in multiple samples of
      subjects with single criterion diagnoses. Subjects who had been assigned to modal
      types according to their correlations with the modal profiles were more similar
      to the modal profile of their assigned groups than to other modal profiles.
      Assigned subjects were more likely to belong to their assigned group than to
      other groups and were more similar to other subjects who had been assigned to the
      same group than to subjects assigned to other groups. Eighty-two percent of
      subjects in the derivation sample were assigned empirically to a modal profile
      group; 77% of subjects in a cross-validation sample were assigned to a modal
      profile group. The discussion focuses on the potential research and clinical use
      of the modal LNNB profiles.

PMID- 14589510
TI  - Verbal problem solving in high functioning autistic individuals.
AB  - The verbal problem-solving and abstract reasoning ability of 25 high-functioning
      autistic individuals ages 11 to 41 was compared with normal controls individually
      matched on age, gender, race, IQ, and educational level. The Twenty Questions
      Procedure was administered using a grid of 42 common objects. Time to complete
      the task, number of correct solutions, and number and type of questions asked
      were analyzed. Results indicated that controls were more often successful in
      achieving solutions, and in formulating constraint seeking questions that
      conceptually grouped, ordered, and sorted the objects. In contrast, the autistics
      relied primarily on guessing. Findings are consistent with prior studies
      reporting a core deficit in autism involving abstract reasoning ability.

PMID- 14589511
TI  - Figural fluency: differential impairment in patients with left versus right
      frontal lobe lesions.
AB  - Based on an experimental study, Jones-Gotman and Milner demonstrated that
      patients with right frontal lobe lesions were impaired on design fluency. We
      sought a clinical adaptation and developed a psychometrically sound technique for
      design fluency. The present study explores the validity of the Ruff Figural
      Fluency Test (RFFT) in discriminating patients with either right frontal or
      nonright frontal lobe lesions. In the first of two studies, six subjects with
      circumscribed focal lesions were given the RFFT and the Jones-Gotman and Milner
      figural fluency task. In the second study, we identified a larger sample of 30
      patients with focal lesions in the right frontal, left frontal, right posterior,
      or left posterior cortex. The results from both studies support the validity of
      the RFFT as a measure which is sensitive to right anterior dysfunction.

PMID- 14589512
TI  - Neuroanatomic and neuropsychological predictors of unawareness of cognitive
      deficit in the vascular population.
AB  - Unawareness of cognitive deficit following brain damage was investigated in a
      sample of 108 cerebrovascular accident patients and 30 orthopaedic controls. The
      purpose of this study was to: 1. investigate the incidence of unawareness, 2.
      test if neurocognitive factors were predictive of unawareness, and 3. determine
      which specific neuroanatomic lesion sites were predictive of the phenomenon.
      Neuroanatomic lesion site was identified by CT/MRI. Unawareness of cognitive
      deficit was assessed using a structured unawareness interview, while
      neurocognitive status was quantified on several indices. Results showed
      unawareness was associated with brain injury (p <.0001), occurred in varying
      degrees of severity in about 40% of the cerebrovascular group, was significantly
      correlated with various neurocognitive indices, and was more frequently
      associated with cortical verses subcortical lesion sites (p <.0001). The results
      could partially be explained by existing theoretical models, but showed that both
      degree of neurocognitive impairment and neuroanatomic lesion site are predictive
      variables of the unawareness phenomenon. The potential clinical use of
      unawareness screening as a part of routine neuropsychological evaluation was
      discussed.

PMID- 14589513
TI  - Impaired depth perception discriminates Alzheimer's dementia from aging and major
      depression.
AB  - Parietal and temporal lesions are known to impair binocular depth perception.
      Clinically meaningful impairment was therefore suspected due to early
      degeneration of these regions in Alzheimer's dementia. Results supported the
      cortical localization described in focal lesion studies. Deficient stereopsis was
      common in dementia (80%) but relatively uncommon in elderly normals (14%) and
      major depressives with cognitive symptoms (31%). Performance was unrelated to
      age, IQ, or severity of cognitive impairment. Testing involves minimal patient
      effort and time (1-2 min). Stereopsis examination may be useful in the diagnosis
      of early dementia, and may reduce false positives associated with depression,
      limited premorbid ability, or normal aging.

PMID- 14589514
TI  - Norms for depressed patients for the California verbal learning test:
      associations with depression severity and self-report of cognitive difficulties.
AB  - This study provides norms for depressed subjects for a widely used test of verbal
      memory, the California Verbal Learning Test (CVLT). Subjects were 156 outpatients
      with major depression tested during a drug washout period. Mean CVLT memory
      scores for these patients were generally between one-half and one standard
      deviation below age- and sex-corrected norms for nondepressed populations.
      Severity of depression in the patients was not associated with memory
      performance, but was associated with self-report of cognitive difficulties. A
      table of age-, sex-, and education-specific norms for the CVLT is provided.

PMID- 14589515
TI  - Sustained attention and inhibitory control in children with sickle cell syndrome.
AB  - Comparing sustained attention and inhibitory control among youth with sickle cell
      syndrome (SCS) and nondiseased sibling controls, this study found significant
      differences in multiple components of attention and inhibitory control as a
      function of chronological age. Older SCS youth were found to have increased
      attention and reflectivity. Although it has been argued that SCS youth without
      overt neurological impairments might evidence microvascular infarction, the
      present study, which employed commonly utilized neurocognitive and behavioral
      measures, does not lend support to the notion of generalized deficits in the
      absence of specific laboratory findings. Disease parameters including hemoglobin
      levels, days hospitalized, and emergency room visits were not significantly
      correlated with performance on any of the measures. Within the limitations of
      this particular study, results were interpreted to refute the notion of disease
      related neurocognitive impairments for SCS youth. Further, the development of
      attentional skills for SCS youth is suggested to proceed similarly to that of
      normally developing youth.

PMID- 14589516
TI  - Assessment of brain impairment with the Rey Auditory Verbal Learning Test: a
      comparison with other neuropsychological measures.
AB  - In this study the effectiveness of The Rey Auditory Verbal Learning Test (AVLT)
      at assessing patients with mixed brain impairment was compared with that of a
      number of other commonly used neuropsychological measures. Subjects were 50
      patients with a mixture of medically confirmed neuropathologies, and 50 controls
      with no evidence of neurological history. Groups were equated for age, education,
      and sex. The AVLT was administered as pan of a full neuropsychological battery.
      Results indicated that all seven AVLT recall trials and the total of Trials I-V
      could significantly differentiate between the two groups (p <.001). The AVLT
      trial V score performed best (U = 457.5, p <.0001), correctly predicting group
      membership for 74% of the subjects. This hit-rate was better than any other
      single test on the Halstead-Reitan or Dodrill batteries, and was surpassed only
      by the Dodrill Discrimination Index. The potential usefulness of this test as
      part of a neuropsychological battery is discussed.

PMID- 14589517
TI  - Lateralized brain damage and performance on trail making A and B, Digit Span
      Forward and Backward, and TPT Memory and Location.
AB  - The present retrospective study was undertaken to determine whether Trail Making
      Test A and B, Digit Span Forward and Backward, and TPT Memory and Location scores
      are differentially sensitive to right or left hemisphere brain damage. Groups of
      patients with right, left, and generalized cerebral lesions and matched normal
      controls were compared. Results showed a relative failure for any individual
      measure, difference, or ratio score to reliably distinguish between right and
      left hemisphere lesions. Patients with diffuse lesions performed significantly
      worse than non-neurologic medical controls and right and left lesion groups on
      Trails A and TPT Memory and Location. Results are discussed in terms of specific
      methodological variables including chronicity of lesion, the nature of the task
      demands, and priming effects.

PMID- 14589518
TI  - Decision strategies for cerebral dysfunction IV: determination of cerebral
      dysfunction.
AB  - The present study examined the contribution of tests that compose the Impairment
      Index with regard to their ability to predict brain impairment. The investigation
      further examines the ability of various other tests, chosen because of their
      observed usefulness in detecting brain impairment. Subjects composing the brain
      damaged group (n = 298) were found to be impaired on both CT and EEG
      examinations. The pseudo-neurological control group (n = 193) consisted of
      patients referred for testing yet all non-neuropsychological tests were normal.
      Discriminant analyses were conducted to determine the weightings of each test as
      well as to determine the overall prediction accuracies of three groupings of
      tests. These analyses demonstrate that tests, not comprising the Impairment
      Index, are of predictive value in determining dysfunction: Thurstone Word Fluency
      and a 60 minute delayed recall from the WMS. Overall prediction accuracies of the
      various test groupings ranged from 73.52% to 78.02%. No statistically significant
      reduction of accuracy resulted with cross validation. All tests of statistically
      predictive value and all prediction results with their corresponding discriminant
      formulas are reported as well as a discussion of the application of these
      findings.

PMID- 14589519
TI  - Neuropsychological skills with motor dysfunctional and motor normal children.
AB  - A group of 40 children was selected from a larger sample based on their
      performance on motor coordination, motor speed, and motor inhibition tasks.
      Twenty of the children were classified as Motor Dysfunctional (MD) and 20 were
      classified as Motor Normal (MN). The groups were compared on several
      neuropsychological measures. The results indicated the MD children were
      significantly lower on a number of measures, particularly those requiring sensory
      integration. There were not significant differences on several of the tasks,
      including those more complex in nature. The results are discussed in relation to
      developmental models of neuropsychological functioning.

PMID- 14589520
TI  - Assessment of behavioral sequelae of traumatic and chemical CNS insult.
AB  - Twenty patients with traumatic head injury and 20 patients with neurotoxic
      chemical exposure completed a 68-item Behavior Inventory listing preinsult versus
      postinsult behavior presence or absence for each item. Forty controls completed
      the same inventory, covering approximately the same intervals of time involved
      with CNS insult group. Whereas controls showed nonsignificant behavior changes on
      any variable, clinical groups reported significant behavior change on the
      majority of behavioral variables. There were some differential changes between
      the two clinical groups. Findings suggest an approach to assessing behavior
      changes due to CNS insult.

PMID- 14589521
TI  - First-Last Names and the Grocery List Selective Reminding Test: two computerized
      measures of everyday verbal learning.
AB  - Data are presented on two computerized tests of everyday verbal learning: Paired
      associate learning of First-Last Names (FLN), and the Grocery List Selective
      Reminding Test (GLSRT). MANOVA and multiple regression analyses demonstrated that
      performance on FLN and GLSRT was most strongly related to age, with significant
      secondary associations found for gender, with females performing better than
      males. Additional factor analysis of FLN and GLSRT supported the construct
      validity of these measures by demonstrating significant associations of
      performance with traditional newopsychological measures of memory and related
      functions, including the Paired Associate Learning and Logical Memory subtests
      from the Wechsler Memory Scale, the Benton Visual Retention Test, and WAIS Digit
      Symbol.

PMID- 14589522
TI  - Dementia as a neuropsychological consequence of chronic occupational exposure to
      polychlorinated biphenyls (PCBs).
AB  - Previous epidemiological and clinical studies of humans exposed to
      polychlorinated biphenyls (PCBs) indicate that the majority of patients have
      neurological complaints (e.g., headache, vertigo, paresthesias, poor memory and
      concentration, fatigue, depression). Since only a small minority of PCB-exposed
      patients demonstrate abnormalities on objective neurological measures (e.g., CT
      scans, EEC, nerve conduction velocity), it is particularly unfortunate that
      objective neuropsychological data has not been published to substantiate patient
      complaints. The present study provides neuropsychological test data on two
      patients exposed to PCBs. In both cases, PCB exposure is documented by an
      analysis of PCB levels in the patients' work environments. Despite the absence of
      abnormalities on CT-scans and EEC, both patients displayed a variety of cognitive
      deficits and emotional disturbance. Serial assessment of one patient with high
      blood levels of PCBs revealed a dementia (sharing certain features with
      Alzheimer's disease) and an organic affective syndrome. Assessment of a second
      patient exposed to PCBs (but with no detectable blood levels of PCBs) suggested
      that his cognitive impairments were not due to PCB exposure. The present study
      provides data which points to the importance and sensitivity of
      neuropsychological examination in cases of PCB-exposure.

PMID- 14589523
TI  - Measuring cognitive processes in patients with Parkinson's disease.
AB  - Parkinsonians and control subjects completed a series of cognitive tasks which
      measured primed semantic retrieval, conceptual organization, and conjoint
      retention. Direct measures of cognitive processing failed to yield the wide range
      intellectual deficit patterns that have been found with parkinsonians.

PMID- 14589524
TI  - Effect of true memory impairment on a test of memory complaint validity.
AB  - The Fifteen-Item Test (FIT) is designed to detect an exaggerated presentation on
      memory assessment. This study examines the extent to which poor FIT performance
      might reflect true - as opposed to exaggerated - memory impairment. Subjects were
      60 persons with mild to severe memory impairment who were not involved in
      litigation or disability proceedings. FIT performance was examined in relation to
      WAIS, WMS, and AVLT variables. The results show the FIT "failure" can result from
      true memory impairment, but that severe memory impairment is generally required
      to "fail." Common qualitative errors in this neurologic population are also
      described. Clinical implications of these findings are discussed, with caution
      against use of the FIT in isolation to address possible exaggerated presentation.

PMID- 14589525
TI  - Remediation of chronic attention deficits in traumatic brain-injured patients.
AB  - The present study evaluated an A-B-A single case design attention-remediation
      program for traumatically brain-injured survivors with chronic attention
      deficits. Four adult male TBI survivors participated in an intensive,
      hierarchically ordered, attention-remediation program based on Posner's four
      component model of attention. No clinically significant improvement was obtained
      on the attentional measures, neuropsychological variables, psychological
      characteristics, activities of daily living, or subjective ratings of changes in
      attentional abilities. The efficacy of this attention-remediation program for TBI
      survivors is examined in light of other outcome studies.

PMID- 14589526
TI  - Self and observer predictions of memory performance in a brain-damaged sample.
AB  - The present study examined the ability of 23 brain-damaged patients and outside
      observers (i.e., close friends or relatives) to predict the patients' performance
      on standard clinical tests of memory. Several tests of verbal and nonverbal
      memory were specifically described in a questionnaire and subjects were asked to
      estimate upcoming performance. Individual subject factors were correlated with
      overall prediction accuracy and specific predictions were correlated with memory
      performance across each test. Individual differences, including memory ability,
      did not significantly influence the findings consistent with the view that memory
      and metamemory reflect independent variables. Although correlations obtained from
      the outside observers overall were higher and more often statistically
      significant, both patients and observers often made comparable predictions of the
      patients' task performance suggesting brain-damaged patients have some ability to
      make accurate self-assessments.

PMID- 14589527
TI  - The intellectual correlates scale and the prediction of premorbid intelligence in
      brain-damaged adults.
AB  - An attempt was made to determine if premorbid intelligence could be estimated in
      brain-damaged persons through the use of regression equations developed from a
      scale of items reflecting interests, attitudes, personal values, and personality
      characteristics that correlated with WAIS-R IQs. A total of 33 adults with no
      reported history of brain damage were used in the item selection study. The
      resulting scale, the Intellectual Correlates Scale (ICS), was then administered
      to 30 brain-damaged persons and a group 28 normal controls, none of whom
      participated in the item selection study. Comparisons between the ICS equations
      for estimating WAIS-RIQs and two sets of demographic equations were made. As
      expected, all estimates of Full-Scale IQs were higher than actual IQs for brain
      damaged subjects, but no differences were found between estimated and actual Full
      Scale scores for normals. Results for Verbal and Performance IQs were more
      complex. Semi-partial correlations were used to compare the ICS equations with
      the corresponding demographic equations to assess the unique contributions of
      each.

PMID- 14589528
TI  - Interventions based on the multiple connections model of reading for
      developmental dyslexia and acquired deep dyslexia.
AB  - This paper deals with intervention strategies for developmental and acquired
      dyslexia. In Study 1 two alternative strategies for developmental surface
      dyslexia (dysfunctional connection between the whole word orthographic code and
      the phonetic or name code) were compared. In both the initial study and
      replication study, a modification of the selective reminding technique was
      superior to a traditional multisensory technique in beginning readers, presumably
      because it facilitated word finding or prelexical access to a phonetic code. In
      Study 2 an adolescent with acquired deep dyslexia (dysfunctional connection
      between letter and phonemic codes) who had had his angular gyrus (site of
      grapheme-phoneme correspondence) surgically removed, recovered reading function
      after a four-month phonemic analysis training program. Further research is needed
      to evaluate the efficacy of theory-based intervention strategies in children with
      developmental reading disorders unrelated to focal lesions and in adults with
      acquired reading disorders related to focal lesions.

PMID- 14589529
TI  - Electrocortical mapping, MRI, and neuropsychological measures: evidence of
      Alzheimer's disease in the presence of vascular lesions.
AB  - We report here a case study of a 76-year-old woman with a high school education,
      whose presenting psychiatric symptomatology indicated dementia of unknown
      etiology. Neuropsychological test results were consistent with AD, but diagnosis
      was complicated by an MRI showing a large right hemisphere cortical infarct and
      scattered subcortical changes leading to a diagnosis of possible AD.
      Electrocortical mapping showed the right hemisphere infarct, and gave independent
      evidence suggestive of AD in the relatively intact left hemisphere. This case
      demonstrates the utility of multidimensional assessment as an aid to differential
      diagnosis.

PMID- 14589530
TI  - Analysis of gender effects upon verbal and visual memory performance in adults.
AB  - This study investigated gender effects on verbal and visual memory performance in
      normal adults (age range 18-91 years). The subjects were 140 volunteers (70 male,
      70 female). Individuals in each male-female pair were matched within three years
      on age and two years on education. Shipley Vocabulary scores for the groups also
      were equivalent. Subjects were administered the Continuous Visual Memory Test
      (CVMT), Visual Reproduction subtest (VR), Verbal Selective Reminding Test (VSRT),
      and Expanded Paired Associate Test (EPAT). Results revealed no differences
      between males and females for either the Acquisition or Delayed phases of the
      CVMT and EPAT. Differences for the Delayed VR task also were not significant.
      Male-female differences for the Immediate VR task were marginally significant,
      although the mean difference was less than one point, females consistently
      outperformed males on the VSRT, particularly in the Acquisition phase.
      Differences on the Delayed task, while statistically significant, averaged only
      12 point.

PMID- 14589531
TI  - Decision strategies in neuropsychology II: determination of age effects on
      neuropsychological performance.
AB  - The relationship of age to neuropsychological test performance was explored on
      the subtests comprising the Halstead-Reitan Battery and allied tests. Performance
      of 192 pseudo-neurologic control patients across 10-year age intervals from 16 to
      65 was analyzed. The findings indicate a strong age-performance effect on spatial
      and more complex integrative tests with peak performance between 25 to 35 years
      of age and a decline thereafter. A lack of significant decline was noted on
      sensory, motor, and language tasks. The findings reveal that there is a
      curvilinear change in performance as a function of age and were discussed with
      regard to the obvious need to modify decision strategies to account for the age
      of the patient.

PMID- 14589532
TI  - Decision strategies in neuropsychology III: the relationship among lateralized
      dysfunction, etiology and depression.
AB  - The present study examines depression as a function of lateralized dysfunction
      and etiology. The proposed hypothesis is: patients with left hemisphere lesions
      would be depressed, whereas patients with right hemisphere lesions would not. A
      total of 61 patients (26 right hemisphere, 35 left hemisphere) having either a
      stroke, tumor, or penetrating head wound, completed the MMPI and were given a
      neuropsychological evaluation. Lesion localization was based on
      electroencephalography and neuroradiological procedures. A regression formula
      derived from the MMPI assessed depression. Two analyses were performed between:
      (i) right and left lesioned groups of mixed etiology and a control group, and
      (ii) right and left cerebrovascular lesioned groups and a control group.
      Potentially confounding factors, such as, diagnosis, demographic factors, degree
      of neuropsychological impairment, presence or absence of aphasia, and lesion
      localization were examined. Regardless of etiology, left and right lesioned
      patients did not significantly differ in their depression score, nor was either
      group considered depressed based on the criteria used in this study to measure
      depression.

PMID- 14589533
TI  - Judgement of mood in music following right hemisphere damage.
AB  - Evidence on hemispheric specialization has implicated the right hemisphere as
      having a special role in the mediation of emotion. Since music is an area in
      which both cognitive and affective aspects of perception can be assessed, the aim
      of this study was to investigate the effect of right hemisphere damage on
      perception of emotional meaning or mood in music. An initial pilot study was
      conducted to select music on which normal subjects were consistent in their
      judgement of musical mood. The musical stimuli consisted of extracts of classical
      piano music. The technique used as a measure of musical mood was the Semantic
      Differential. Tracks of music and adjectival scales were selected for the
      experimental study in which 15 right hemisphere lesioned patients and normal
      controls were compared in their response to music. The right hemisphere group
      demonstrated a characteristic response in their judgement of mood in music. The
      results are discussed in terms of the role of pitch in judgement of mood in music
      and in terms of the relationship between music and language.

PMID- 14589534
TI  - A national survey of psychologists who offer neuropsychological services.
AB  - We conducted a national survey of psychologists who offer neuropsychological
      services to determine levels of training, current practices, and views on
      professional issues. All subjects were listed in the National Register of Health
      Service Providers in Psychology and/or the American Psychological Association
      Directory as having some affiliation with neuropsychology. Results suggest marked
      diversity within the field, with the modal practitioner being minimally involved
      in neuropsychological activities. We also compare clinicians with varying
      involvement and experience in neuropsychology and analyze the concentration of
      practitioners by geographic regions. We compare our results to those obtained in
      prior surveys and discuss implications of the findings.

PMID- 14589535
TI  - Increased false alarms in a subset of persons at-risk for Huntington's disease.
AB  - The accuracy and decision criterion of 51 persons at-risk (AR) for Huntington's
      disease (HD) along with 36 age-matched, healthy controls were evaluated using a
      word recognition memory test. Analyses revealed that the AR group was less
      accurate than the controls at recognizing a previously learned word list. Within
      the AR group, 13 AR persons were identified who committed significantly more
      false alarms than the remaining AR and control people. The 13 AR persons also
      showed evidence of lower cerebral metabolic ratios in frontal, caudate, and
      insula regions, as evaluated by positron emission tomography using I8F-Fluoro
      deoxyglucose, and were considered to be at high risk for HD. One of these 13 AR
      persons has become symptomatic since testing, confirming the high risk status.
      These results suggest that certain tests of cognition and decision-making
      together with measures of regional brain metabolism might show the subtle
      cognitive changes taking place in potential HD gene carriers years before the
      clinical symptoms are observed.

PMID- 14589536
TI  - Alternate forms of the AVLT: a procedure and test of form equivalency.
AB  - The Rey Auditory Verbal Learning Test is frequently used in neuropsychological
      evaluation and research. However, its utility in the measurement of progressive
      change is limited by the availability of alternate and equivalent forms. Criteria
      were developed for word selection to generate new lists. Two alternate forms
      generated according to these criteria, as well as the original Key AVLT and
      alternate form, were administered to elderly Medical Center patients and
      undergraduate volunteers. All four AVLT forms yielded comparable mean recall
      scores, and alternate form reliability coefficients for each trial varied from.67
      to.90. Conclusions from this study, though, must be made with caution as the
      sample size used was small.

PMID- 14589537
TI  - Frontal lobe functioning in conduct disordered juveniles: preliminary findings.
AB  - This investigation assessed the hypothesis that conduct disordered juveniles may
      suffer from a maturational lag in the development of behaviors believed
      associated with the frontal cortex. Twenty conduct disorder (CD) juveniles and 20
      normal comparison subjects were compared on nine Lurian tasks that measure
      behavior attributed to frontal lobe functioning. A three-way ANOVA, with gender,
      race, and group as factors of interest, revealed significant differences on the
      verbal conflict task, verbal retroactive inhibition task, and on a measure of
      receptive vocabulary. Using receptive vocabulary as a covariate, an ANCOVA showed
      no significant differences between the groups on any of the tasks. These findings
      appear to support the potential impact that language dysfunction can have in the
      development of disinhibitory behavior. Other interpretations of the findings are
      presented.

PMID- 14589538
TI  - A comparison of the Rey and Taylor figures.
AB  - Forty healthy young adults were given the Rey-Osterrieth or Taylor Complex
      Figures in order to evaluate the comparability of these two measures. Copy trials
      of the Rey and Taylor Figures proved to be of equivalent difficulty. By contrast,
      30-minute delayed recall of the Rey Figure was considerably more difficult than
      that of the Taylor Figure.

PMID- 14589539
TI  - Psychometric construction of the Rey-Osterrieth Complex Figure: methodological
      considerations and interrater reliability.
AB  - Formal scoring criteria for the standard 18 elements of the Rey-Osterrieth
      Complex Figure were developed and applied to reproductions of 87 healthy young
      adults. In addition, the effects of immediate recall on delayed performance was
      investigated. Results indicate (a) the formal scoring criteria can be reliably
      applied by independent raters; (b) 30-minute recall is significantly higher if
      immediate reproduction is included compared to 30-minute delay performance
      without immediate recall; (c) significantly fewer qualitative scoring errors are
      present at the 30-minute delay if immediate memory is previously assessed; and
      (d) in addition to an absence of decay over a 30-minute delay, performance
      significantly improves over this interval. These findings underscore the caution
      that must be exercised when making specific inferences from test scores alone
      based upon measures that were obtained in a variety of contexts employing
      unspecified scoring criteria.

PMID- 14589540
TI  - Factors affecting adjustment of parents of head trauma victims.
AB  - This study was aimed at elucidating the factors associated with good and poor
      adjustment in the parents of adult head trauma victims. Forty-eight parents of
      adult trauma victims were administered the Hassles Scale, the Ways of Coping
      Inventory, the SCL-90, and the Sickness Impact Profile. The following results
      were obtained: 1. Psychosocial dysfunction in the offspring was correlated with
      severity of stress in the parents. 2. Psychiatric maladjustment in the parent was
      associated with increased stress. 3. Parents poor emotional adjustment were more
      inclined to use coping strategies involving confrontation or avoidance.

PMID- 14589541
TI  - Normal aging and forgetting rates on the Wechsler Memory Scale-Revised.
AB  - The deleterious effects of aging on various cognitive abilities are widely
      recognized, yet little is known regarding what constitutes "normal" memory test
      performance in individuals over the age of 74. In this study, forgetting rates
      for verbal and nonverbal material from the Wechsler Memory Scale-Revised (WMS-R)
      were examined in groups of older healthy individuals, age 50-70 and 75-95.
      Despite equivalent scores on measures of global cognitive status and attention/
      concentration, the older group demonstrated significantly more rapid forgetting
      rates on the Visual Reproduction, Verbal Paired Associates, and Visual Paired
      Associates subtests of the WMS-R. Although patients with Alzheimer's disease also
      evidence very rapid forgetting on some subtests, the severity and pattern of
      losses appears useful in differentiating "abnormal" forgetting from that
      exhibited by normal elderly subjects. Preliminary normative data for normal
      elderly subjects on the WMS-R are presented, and the need for appropriate norms
      for elderly individuals is discussed.

PMID- 14589542
TI  - Neuropsychological sequelae of exposure to the chlorinated hydrocarbon solvents
      trichloroethylene and trichloroethane.
AB  - Reports in the literature concerning the acute neurobehavioral effects of
      trichloroethylene (TCE) and trichloroethane (TCA) conflict as to whether or not
      cognitive deficits ensue. Our study of two patients acutely exposed to low
      concentrations of TCE suggests that (a) acute, low-dose exposures are sufficient
      to produce the mild to moderate impairments in psychomotor speed, attention and
      memory also reported after chronic exposures; (b) these memory impairments may be
      characterized by storage and/or retrieval difficulties; (c) the neural damage
      produced by TCE exposure is likely to be diffuse, but temporal lobe structures
      supporting memory may be more sensitive to TCE exposure than other brain
      structures; and (d) even brief exposures can lead to prolonged, but not
      necessarily chronic mild to moderate cognitive impairment. In a third case,
      exposed to trichloroethane (TCA), the neuropsychological profile suggests that
      this substance has few, if any, neurobehavioral effects at low concentrations.

PMID- 14589543
TI  - Intrusion errors in the figural memory of patients with Alzheimer's and
      Huntington's disease.
AB  - The tendency of patients with dementia of the Alzheimer type (DAT) and
      Huntington's disease (HD) to produce prior-item intrusion errors on a figural
      memory task was assessed. Patients' and elderly control subjects' immediate
      recall of figures from the Visual Reproduction Test (VRT) of the Wechsler Memory
      Scale (WMS) was scored for the presence of prior-figure intrusion errors (i.e.,
      characteristics unique to one figure included in the reproduction of a subsequent
      figure). Results indicate that both patient groups produced more prior-figure
      intrusion errors than did the NC group, and that DAT patients made significantly
      more intrusion errors in their reproductions than did HD patients matched for
      overall severity of dementia. These data suggest that prior-item intrusion errors
      are evident on figural as well as on verbal memory tasks and that DAT patients
      are more likely to produce such errors than are equally demented patients with a
      "subcortical" dementia.

PMID- 14589544
TI  - Memory disturbances following chronic, low-level carbon monoxide exposure.
AB  - Neuropsychiatric sequelae are a common feature of acute carbon-monoxide (CO)
      poisoning-particularly when the patient has experienced an episode of CO-induced
      unconsciousness. In this case report, we present neuropsychological test data
      demonstrating the presence of mild cognitive impairments following a chronic (3
      year) history of low-level CO exposure that never produced loss of consciousness.
      Deficits were limited to concentration and memory; performance on measures of
      general intelligence, visuospatial functioning, and speed and dexterity were well
      within the normal range.

PMID- 14589545
TI  - Credentials and clinical activities of internship supervisors in neuropsychology:
      a comparison of VA and non-VA training sites.
AB  - Surveyed 69 VA and 101 non-VA internships to (a) delineate the credentials and
      activities of supervisors in clinical neuropsychology, and (b) compare the
      credentials and activities of the two groups. Questionnaires were returned by 83%
      of VA and 62% of non-VA internships. A majority of each group was trained in
      clinical psychology. The proportions of supervisors with board certification and
      relevant coursework and/or training experiences (e.g., postdoctoral fellowship)
      were the same for both groups. Similarities were noted in time devoted to
      research and training, number of interns supervised, preferred assessment tools,
      and favored approach to clinical evaluation. Conversely, VA instructors devoted
      more time to clinical practice, while non-VA personnel claimed more publications.
      The majority of VA supervisors were trained in VA settings, while most non-VA
      respondents interned at university medical centers or state hospitals. The
      training and credentials of both groups evidenced wide ranging competencies. The
      need for improved training and credentialing of practitioners and supervisors was
      discussed.

PMID- 14589546
TI  - Depression and neuropsychological test performance in acute spinal cord injury
      patients: lack of correlation.
AB  - Factors which have been causally related to neuropsychological deficits in acute
      spinal cord injury (SCI) patients include advanced age, limited educational
      level, acute traumatic brain injury, alcohol and/or substance abuse. Concomitant
      depression may impair motivation, prolong reaction time, and produce fatigue
      during neuropsychological testing, resulting in impaired performance. To test the
      hypothesis that abnormal neuropsychologic test results may be associated with
      depression, the Zung Self-Rating Depression Scale (ZUNG) and a comprehensive,
      predominantly motor-free neuropsychological test battery were administered to 66
      acute SCI patients approximately 8 weeks following injury. Spinal cord injury
      groups were dichotomized based on their ZUNG scores. Comparison of
      neuropsychological test scores between SCI groups failed to demonstrate any
      impairment in neuropsychological performance, within the limits of the test
      battery administered, suggesting that cognitive performance in this sample of
      acute SCI patients may not be influenced by the presence of depression.

PMID- 14589547
TI  - MRI and neuropsychological correlates of dementia in Binswanger's disease.
AB  - Nuclear magnetic resonance imaging (MRI) has facilitated diagnosis of
      Binswanger's disease in vivo, which has proven to be a more common disease entity
      than once believed. These patients generally present with hypertension,
      progressive dementia, hydrocephalus, gait difficulty, and personality change. A
      patient is presented with MRI findings of white-matter destruction and
      subcortical lesions, and with neuropsychological findings of higher-order
      cognitive impairment but selectively preserved language and visuospatial
      perceptual skills. The relationship between the patient's cognitive-behavioral
      symptoms and the presence of disconnection syndrome is discussed. In addition,
      the utility of neuropsychological examination is reviewed. Finally, implications
      for differentiating cortical from subcortical dementia with psychometric test
      data are discussed.

PMID- 14589549
TI  - Color discrimination testing reveals early printshop solvent neurotoxicity better
      than a neuropsychological test battery.
AB  - Twenty standardized neuropsychological tests were compared to the Lanthony D-15
      desaturated panel test of chromotopsia to determine which measures would most
      effectively discriminate solvent-exposed print workers from controls. All the
      workers of the printing services of Universite du Quebec a Montreal (N = 29) were
      assessed excepted one who refused to participate. Twenty-nine workers (employed
      on a full time basis) matched for occupation, age, sex, education, vocabulary,
      and written arithmetic (p >.13) with the print workers served as controls. Air
      samples revealed exposure to ethanol, perchloroethylene, methyl chloride, xylene,
      toluene, and stoddard solvent in the print shop. None of the 20
      neuropsychological measures yielded a statistically significant decrement in the
      print workers. On the other hand, the Lanthony D-15 test revealed a significant
      group difference (p <.01) and a highly significant interaction between job
      category within the print shop and dyschromatopsia (p <.001) - the graphists,
      photocopiers, and printers/binders manifesting increasing severity of impairment
      as a function of increasing magnitude, and/or type, of dose. The results were
      interpreted to mean that in a cohort of printers with low seniority (10.42 years)
      such as this one, neuro-opthalmotoxic effects can be observed earlier than
      putative neuropsychotoxic effects with the tools at hand.

PMID- 14589550
TI  - Factor structure of the Wechsler memory scale-revised in relation to age and
      educational level.
AB  - The factor structure of the Wechsler Memory Scale-Revised was examined for 3 age
      groups (<or=39, 40-55, >or= 56) and three educational levels (< 12, 12. > 12) in
      a large group of patients (n = 434) referred for examination at two large medical
      centers. The subtests of the Wechsler Memory Scale Revised were subjected to
      principal components factor analyses. A separate set of analyses were performed
      that included the Verbal IQ and Performance IQ scores from the WAIS-R. Consistent
      with previous reports of age related changes in spatial function there appeared
      to be somewhat greater loading of nonverbal memory tests on verbal factors with
      increasing age. Inclusion of IQ scores appeared to have an affect on the content
      and relative prominence of the various factors in those subgroups formed on the
      basis of educational level. The results are discussed in regard to clinical use
      of the WMS-R and directions for future research.

PMID- 14589551
TI  - Effects of visual acuity and visual motor speed and dexterity on cognitive test
      performance.
AB  - This study examined the hypothesis that near visual acuity and visual motor speed
      and dexterity contribute significantly to performance on cognitive tests that
      place a premium on these functions. Near visual acuity for both eyes, Finger
      Tapping Test - average taps with dominant hand, and Grooved Pegboard Test -
      dominant hand time, served as the independent variables. The dependent variables
      were Trail Making Test-Part B and the Performance subtests of the Wechsler Adult
      Intelligence Scale. Results indicated that while visual acuity was significantly
      correlated with all six test variables, it did not contribute to the regression
      model as well as Pegboard time or Tapping speed. Pegboard time and Tapping speed
      contributed to the regression model, but in different ways depending upon which
      test was examined.

PMID- 14589552
TI  - Lateralized cerebral dysfunction in schizophrenia and depression: gender and
      medication effects.
AB  - The neuropsychological functioning of 52 schizophrenic and 39 major depressive
      patients was examined using the four Luria-Nebraska Neuropsychological Battery
      lateralization scales, with the effects of gender and medication status examined
      alone and in interaction with diagnosis and laterality variables. Comparisons
      between the diagnostic groups revealed that gender influences some aspects of
      neuropsychological performance, particularly those involving bilateral complex
      cognitive-perceptual rather than sensorimotor skills. This effect was more
      distinct for depressives than schizophrenics when cerebral lateralization
      differences were present. There was no significant left hemisphere disadvantage
      for schizophrenics which was gender-related. Medication status revealed no
      appreciable effects for depressives, although both male and female schizophrenics
      receiving neuroleptics showed a greater degree of complex perceptual-cognitive
      dysfunction compared to unmedicated schizophrenics. Level of cerebral impairment
      was equivalent for the right and left hemispheres for both groups. Consequently,
      these data are not consistent with other findings demonstrating differential
      hemispheric disadvantages between schizophrenia and depression.

PMID- 14589553
TI  - Cognitive processing strategies for normal and LD children: a comparison of the K
      ABC and microcomputer experiments.
AB  - The purpose of this study was to investigate: (a) whether the cognitive
      processing Strategies employed on a visual-spatial and a verbal-analytic
      experiment differ for LD and normal readers; (b) the relationship between
      performance on the experimental tasks and the Kaufman Assessment Battery (K-ABC)
      Scales; and (c) the discriminating power of the experiments and the K-ABC for
      differentiating LD children from normal readers. Thirty-seven controls were
      matched by age, grade (4th-6th), and sex to 36 LD children. Univariate F tests
      show that the normal group scored higher on the K-ABC Scales; and, the two groups
      differed in terms of the processing Strategies used on a visual-spatial and a
      verbal-analytic experiment. Subjects did not demonstrate consistent processing
      Strategies on the K-ABC, the visual-spatial and the verbal-analytic experiments.
      Discriminant analysis showed that the visual-spatial and the verbal-analytic
      experiments had higher classification accuracy rates than did the K-ABC Scales.
      These results indicate that LD children do use different processing Strategies
      than do normal readers on a variety of tasks; however, neither group showed
      "consistent" Strategies across all tasks.

PMID- 14589554
TI  - Handedness and reading disability: a developmental study.
AB  - 124 normal children were followed from age 5 to 9. Manual laterality status
      continues to consolidate between these ages and reveals itself unrelated to
      reading level.

PMID- 14589555
TI  - Regional cerebral blood flow (rCBF) in normal readers: bilateral activation with
      narrative text.
AB  - Based on recent evidence that suggests a more active participation of the right
      cerebral hemisphere in reading, this exploratory study examined changes in
      regional cerebral blood flow (rCBF) in three normal subjects during the reading
      of controlled narrative text. Narrative text presumably activates all
      neurocognitive processes important in reading including the semantic, pragmatic,
      emotional, and imagery components. Because of the small number of subjects,
      percentage change over a baseline at rest condition in rCBF during reading was
      compared to test/retest variability in control subjects. Effect size was also
      considered. The results indicated statistically significant bilateral central
      posterior activation during reading. These findings are consistent with an
      evolving model of bilateral language representation in which subcortical
      structures and right hemispheric systems are functionally and anatomically tied
      to the dominant left hemispheric language centers.

PMID- 14589559
TI  - Editorial: software survey section.

PMID- 14589556
TI  - Depression preceding choreiform movements in Huntington's Disease: a case study.
AB  - Huntington's Disease (HD) is a progressive neurological disorder whose cardinal
      features are involuntary movements and cognitive decline. Severe emotional and/
      or psychiatric disturbances are common features of the mental deterioration. When
      the emotional disturbance precedes the development of the movement disorder, HD
      is often misdiagnosed as a psychiatric condition. The present case study taken
      from the University of Texas Neuropathology Museum illustrates these issues. The
      patient was diagnosed and treated for depression for over a decade before the
      behavioral and neurological deterioration progressed to the point that an HD
      diagnosis could be made. Only with the detection of a positive family history and
      the onset of the hallmark choreiform movements was the final diagnosis of HD
      made. The patient's behavioral features are presented and current pathological
      and neuropsychological findings in HD are reviewed and discussed.

PMID- 14589560
TI  - Hemispherectomy and diaschisis: rapid improvement in cerebral functions after
      right hemispherectomy in a six year old child.
AB  - Neuroradiological, neurological, and neuropsychological studies before and after
      hemispherectomy for seizures of a six year old boy with left hemiplegia at birth
      revealed striking postoperative improvement. Seizures ceased and have not
      recurred. Preoperative EEC studies from seven months of age revealed increasing
      pathological involvement of the left as well as right hemisphere.
      Postoperatively, normal tracings over the left hemisphere documented marked and
      continuing improvement. In contrast to markedly subnormal preoperative WISC-R
      IQs, retest at 19 months postoperatively showed WISC-R IQs within the normal
      range, with similar improvement in other tests of cognitive, motor and sensory
      functions. The arrest and reversal of the preoperative pattern of increasing
      deterioration and disappearance of pathological involvement of left as well as
      right hemisphere functions following surgery is consistent with the disappearance
      of diaschisis as described by von Monakow in 1914, and has conceivably
      significant clinical as well as theoretical implications.

PMID- 14589561
TI  - Simultaneous and successive cognitive processes in brain damaged adults:
      hemispheric and anterior-posterior effects.
AB  - The relationship between simultaneous and successive processing and their assumed
      underlying neuro-anatomical structures was examined. According to the model of
      Das, Kirby, and Jarman (1975, 1979) simultaneous processing, occurs mainly in the
      posterior parts of the brain (parieto-occipital areas) and successive processing
      in anterior regions of the brain (fronto-temporal areas). The theory of
      lateralized hemispheric specialization suggests differences in processing due to
      right-left hemispheric differences. A battery of measures was factor-analyzed and
      simultaneous and successive factors identified in 106 brain-damaged adults and a
      control group. The brain damaged group was divided into four subgroups, left and
      right anterior and left and right posterior groups. The two-way ANOVA revealed no
      interactions (laterality x anterior/posterior), but instead two main effects for
      laterality on simultaneous verbal (p<.01) and successive (p<.05) processing and
      one weak (p<. 10) main effect for anterior/posterior divisions of simultaneous
      nonverbal processing. It was concluded that the results partially supported both
      assumed neuropsychological models of processing.

PMID- 14589562
TI  - Relationships between the WAIS and neuropsychological measures for
      neuropsychiatric inpatients.
AB  - The current study examines the sensitivity of the Wechsler Adult Intelligence
      Scale in predicting performance on a modified Halstead Neuropsychological Test
      Battery for lower-functioning neuropsychiatric inpatients (97 men, 54 women).
      Regression analyses support earlier-reported findings that the WAIS's subtests
      more accurately predict neuropsychological test performance than do the WAIS IQ's
      alone. The IQ's and scaled scores respectively predicted 27% and 39% of the
      variance in the Halstead's measures. The overall relationship between
      neurocognitive and WAIS indices is somewhat greater than previous reports and is
      apparently due to the fact that the lower the overall level of cognitive ability,
      the lower is neuropsychological functioning in general. However, since most of
      the variance in the modified Halstead Battery was not common with the WAIS's
      indices, these findings continue to support the practice of including both sets
      of measures as part of a comprehensive neuropsychological assessment paradigm for
      such patients. The importance of developing instruments and procedures which more
      precisely measure "fluid" neurocognitive abilities is underscored.

PMID- 14589563
TI  - Paired associate learning: form 1 and form 2 of the Wechsler Memory Scale.
AB  - Despite its popularity as a clinical measure, the paired Associate Learning (PAL)
      subtest of Wechsler's Memory Scale (WMS) still remains relatively undocumented
      for its psychometric properties. This article reports on the performance of 500
      (form 1) and 600 (form 2) general medical patients hospitalized for other than
      neuropsychiatric conditions across five (20-69) and six (20-79) ten-year age
      bands respectively. In both alternate forms of PAL, strong age effects emerged
      while sex differences were more marked in form 2. Temporal reliability, assessed
      in separate student samples, proved adequate for either form. Parallel form
      correlations also indicated a moderate relationship between them. When easy and
      hard associates were analysed as separate measures with MANOVA the two forms were
      found to differ. Some possible reasons for these results are explored with
      respect to current information processing concepts postulated to affect verbal
      learning performance, and their utility in helping distinguish between
      pseudodementia and mild Alzheimer type dementia. Separate factor analyses also
      showed the two equivalent forms to diverge somewhat in their structural pattern
      with form 1 demonstrating clear clusterings of the pairs along a continuum
      ranging from very easy (overlearned) and mediate (superordinate) to hard
      associates.

PMID- 14589564
TI  - What does the neuropsychological category test measure?
AB  - The Halstead Category Test of brain dysfunction is one of the most sensitive
      neuropsychological measures currently available. While the instrument has
      received widespread use, nevertheless, the exact nature of what it measures has
      been poorly delineated. The present brief report presents the results of separate
      factor analyses of the Category Test along with other neuropsychological measures
      from the Halstead-Reitan battery. Despite considerable differences in samples, as
      well as in the particular neuropsychological measures included in the separate
      analyses, the Category Test consistently lined-up with general intellectual and
      memory components, in each instance.

PMID- 14589566
TI  - The neuropsychology of hydrocephalus.
AB  - The relationship between neuropsychological impairment and hydrocephalus is
      reviewed and three case studies presented. Current brain imaging technology
      provides a method for detailed quantification of ventricular expansion and
      alteration or loss of cortical tissue in hydrocephalus. However, there appears to
      be little systematic relationship between ventricular size in hydrocephalus and
      the type or degree of neuropsychological impairment. As a group, hydrocephalic
      patients do demonstrate a variety of cognitive and perceptual-motor deficits, but
      there does not appear to be a common diagnostic neuropsychological pattern in
      hydrocephalus although perceptual-motor/manipulo-spatial deficits appear to
      predominate. It appears that there is considerable neural plasticity that occurs
      in some patients with congenital hydrocephalus and much of this functional
      reorganization may take place at subcortical and subtentorial levels. Clinical
      guidelines for the neuropsychological assessment of hydrocephalus are given.

PMID- 14589567
TI  - Age group differences on neuropsychological battery performance in a
      neuropsychiatric population: an international descriptive study with
      replications.
AB  - The relationship of age to performance on the Halstead-Reitan Neuropsychological
      Battery was examined in three samples drawn from neuropsychiatric populations: an
      initial sample of 217 subjects, a within-laboratory replication of 307 subjects,
      and a cross-national replication sample of 101 subjects. The results showed
      significant relationships of age to subtests of the Halstead-Reitan Battery
      involving problem-solving abilities and motor strength, which were replicated
      across the three samples. Verbal and perceptual subtests were not consistently
      related to age across samples. For those problem-solving and motor tests showing
      replicated correlations with age. mean scores are provided for three age groups
      (16-34, 35-54, and 55 and above), and group differences were tested with analysis
      of variance. These results help clarify for which measures age group differences
      are consistent in neuropsychiatric populations. Implications of these results for
      treatment program planning are discussed

PMID- 14589568
TI  - Construct validity of the San Diego Neuropsychological Test Battery.
AB  - A group of 259 normal adults were administered the San Diego Neuropsychological
      Test Battery. Factor analysis of the SDNB supported the construct validity of the
      battery according to a Luria-based functional systems assessment approach. Using
      expert ratings to interpret the obtained factor loadings, the following factors
      were identified: (a) arousal, (b) mnestic processes, (c) complex intelligence,
      and (d) planning. A second factor analysis of the SDNB, using a sample of 100
      schizophrenic and head injured cases, achieved a factor structure very similar to
      that of the normal sample, offering further empirical support for a functional
      assessment approach with clinical populations. The clinical factor analysis
      yielded slightly different proportions of variance contributed by the test
      measures and two planning factors. The results are discussed as they relate to
      Luria's qualitative analysis of cortical organization applied to a quantitative
      methodology.

PMID- 14589569
TI  - Retraining social and adaptive living skills in severely head injured adults.
AB  - To assess the effectiveness of an intensive, multidisciplinary rehabilitation
      program upon social and adaptive living skills, and to study the relationship of
      cognitive functioning to those skills, 10 severely head-injured adults who were
      treated in the program were matched with 10 waiting-list control subjects. The
      mean improvement shown by the treated subjects in social and adaptive living
      skills were all in the expected direction and all greater than the mean changes
      of control subjects, though not significantly so. Cognitive changes showed no
      consistent patterns. A striking bimodal distribution in the results for social
      and adaptive living skills suggests that future researchers should consider
      employing single-subject methodology coupled with a knowledge of the patterns and
      events that occur during each individual's recovery sequence.

PMID- 14589570
TI  - Neuropsychological toxicology: identification and assessment of neurotoxic
      syndromes.
AB  - Neuropsychological toxicology, or, more commonly, "neurobehavioral toxicology" is
      the study of how naturally or industrially produced nervous system poisons effect
      neuropsychological functioning. Research of this sort has been widely
      disseminated in European and Scandinavian medical literature during the past two
      decades but is only just beginning to enter neuropsychological literature of the
      United States. Neuropsychological sequelae of several representative human
      neurotoxins are briefly reviewed, including metallic lead, the solvent toluene,
      organophosphate pesticides and antihypertensive medication. These substances
      represent exemplars from some of the major classes of potentially neurotoxic
      substances; metals, solvents, pesticides, and prescription drugs. They are also
      examples of neurotoxins that have been examined with neuropsychological methods
      and for which neuropsychological symptoms or syndromes have been discovered.
      Testing procedures sensitive to neurotoxic exposure are also summarized. The role
      of the neuropsychologist as neurobehavioral toxicologist is explored. It is
      suggested that the neuropsychologist is in a unique position to perform research
      and clinical evaluations relating to neurotoxic exposure, and that the sub
      clinical effects of neurotoxic exposure may be most sensitively discovered with
      these methods. Further, neurotoxic effects may be subject to misdiagnosis without
      knowledge of how to examine for these substances. The future expansion of
      neuropsychology into "neuropsychological toxicology" is advocated.

PMID- 14589571
TI  - National standardization of the Auditory Discrimination Test: normative and
      reliability results.
AB  - The Auditory Discrimination Test (ADT), which consists of two alternate forms
      (Forms 1A and 2A), has been used extensively in clinical, educational, and
      research settings for nearly 30 years. Until now, two major problems with the
      clinical and educational use of the ADT have been the lack of representative
      norms, and the somewhat restricted age range of the test. This article reports on
      a national standardization of the ADT, and an extension of this test downward for
      use with four year old children. The sample included over 1.800 children from
      public and private elementary and preschool settings who were selected from over
      30 states across the country. The sample was stratified on the basis of
      geographic region, age, sex, ethnic background, parent's occupation, and
      community size. Results indicated developmental differences in auditory
      discrimination as assessed by the ADT, substantiating the utility of age level
      norms. In addition, internal consistency reliability was computed for all age
      levels on the ADT. A median reliability of.78 was found for ADT Form 1A, and.81
      for ADT Form 2A, with higher reliabilities found at the younger ages. Overall,
      the results of this investigation suggest that the ADT is a useful measure of
      auditory discrimination in young children. Furthermore, the development of
      national, stratified norms provides renewed utility for the application of test
      results in norm-referenced decision situations.

PMID- 14589572
TI  - Epilepsy, neuropsychological deficits, and EEG lateralization.
AB  - One hundred eight epileptic patients (59 men, 49 women; 55% partial seizures, 45%
      generalized) were examined on 45 indices comprising a modified Halstead
      Neuropsychological Test Battery. Factor analyses identified five dimensions:
      Verbal Comprehension, Perceptual Organization, Selective Attention, Motor Skills,
      Abstract Reasoning. These factors are similar to those previously reported for
      neurocognitive abilities in several different populations. Relative deficits on
      Verbal Comprehension and Abstract Reasoning were related, as predicted, to left
      hemispheric dysfunction as indexed by EEG localization. Perceptual Organization
      demonstrated a further, predictable relationship to right hemispheric function.
      Deficits on Selective Attention were not clearly lateralized, being correlated
      with a wide variety of electroencephalographic abnormalities. The implications of
      these findings for the use of neurocognitive profiles in treatment planning for
      this population are discussed.

PMID- 14589573
TI  - Catastrophic minor head trauma.
AB  - The neurologic and neuropsychologic sequelae of Acquired Immune Deficiency
      Syndrome (AIDS) have received an increasing amount of attention recently. A
      variety of neurologic disorders are now associated with AIDS or AIDS-Related
      Complex (ARC). To date, however, there have been no detailed accounts of the
      behavioral sequelae or course of illness of AIDS/ARC victims who have suffered
      brain trauma. This paper describes the case of a 39 year old male patient who
      tested positive for the retrovirus now associated with AIDS/ARC (Human T
      Lymphatropic Virus Type III or "HTLV-III") and suffered a closed head injury as a
      consequence of a physical assault. His course was rapid and his symptomatology
      more profound than would be expected on the basis of his injury alone. The
      assault is regarded as a second, catalytic injury and is presumed to derive its
      pronounced effect from the ongoing neurologic disorder resulting from or
      associated with the HTLV-III virus. The possible role of head injury in the
      exacerbation of diffuse and subclinical cortical dysfunction is discussed.
      Relevant contributions from sports medicine literature and Alzheimer's Disease
      research are reviewed.

PMID- 14589574
TI  - Relationship between systolic and diastolic blood pressure and cognitive
      functioning in hypertensive subjects: an extension of previous findings.
AB  - The relationship between blood pressure and neuropsychological functioning in a
      group of 15 male hypertensives (mean age = 51.2 years) was studied. Thirteen of
      the 15 subjects showed cognitive deficits on a battery of neuropsychological
      tests. More significant negative correlations were found among test scores and
      systolic pressure than diastolic pressure. Stepwise multiple regression analyses
      confirmed significant relationships between both systolic and diastolic blood
      pressure and neuropsychological status. Following biofeedback training, subjects
      in whom blood pressure decreased the most showed the greatest improvement in
      Category Test performance. Findings suggest that level of systolic pressure is a
      sensitive predictor of hypertensives' intellectual and cognitive status, that it
      may be better than diastolic level, and that decreasing blood pressure is
      predictive of reversal of at least some of the cognitive impairments associated
      with hypertension.

PMID- 14589575
TI  - Normative problems for the Wechsler Memory Scale-revised logical memory test when
      used in litigation.
AB  - A sample of 100 neuropsychologically normal worker's compensation claimants was
      evaluated with the Trail Making Test, the Logical Memory Test of the Wechsler
      Memory Scale-Revised (WMS-R) (immediate and delayed) and the (MMPI) to determine
      the appropriateness of the Logical Memory norms for individuals in litigation.
      Results indicate these claimants performed below normal, possibly due to
      depression or poor motivation while age and education were not important factors.
      The danger of using such norms uncritically in litigation cases is discussed.

PMID- 14589576
TI  - Frontal lobe functioning in geriatric and non-geriatric samples: an argument for
      multimodal analyses.
AB  - The present investigation examines specific aspects of frontal functioning across
      geriatric and nongeriatric cohorts. Subjects included 193 nongeriatric male
      pilots (mean age: 48.29 (SD = 6.79); mean education: 15.93 years (SD = 1.86)),
      and 68 geriatric males and females (mean age: 78.38 (SD = 5.07); mean education:
      13.68 (SD = 2.53)). The results of a series of general linear model multivariate
      one-way analyses revealed poorer performance on frontal measures in the geriatric
      sample, although no differences were noted between the male and female samples.
      In contrast, variable interrelations, as assessed by a parametric statistic of
      betweengroup factor similarity, indicated a noteworthy similarity of factors
      between the geriatric and nongeriatric groups, and dissimilarities between the
      factor structures for males and geriatric females. These findings not only
      support the presence of age-related differences in frontal performance for the
      domains tested, they suggest the need to examine frontal functioning by multiple
      methods, as differences in frontal functioning may exist between groups that are
      undetected by analyses based on intergroup score differences or predictor
      criterion correlations alone

PMID- 14589577
TI  - Effects of temporal lobectomy on generative fluency and other language functions.
AB  - We investigated the acute effects of unilateral temporal lobectomy on multiple
      language measures and standardized generative word fluency tasks, as well as
      longer term effects measured 1 year following surgery. All patients were left
      cerebral dominant for language functioning as determined by Wada testing. Results
      indicate consistent acute language decline for left but not right temporal
      lobectomy patients. In contrast, verbal generative fluency decreased independent
      of lesion laterality, suggesting diffuse acute lesion effects on certain tasks
      mediated primarily by the left hemisphere. When examining language performance in
      an independent patient group at their 1-year follow-up assessment, no negative
      surgery effects were present on any language measure. Further, significant
      improvement over baseline performance for word fluency was present 1 year
      following surgery. In the acute assessment of cognition following temporal
      lobectomy, the relative sensitivity of neuropsychological measures to acute
      cerebral lesions should be considered.

PMID- 14589579
TI  - Neurodiagnostic implications of abnormal verbal-performance IQ discrepancies on
      the WAIS-R: a comparison with the standardization sample.
AB  - The neurodiagnostic value of Wechsler Adult Intelligence Scale-Revised (WAIS-R)
      Verbal-Performance IQ (VIQ-PIQ) discrepancies was evaluated in a brain-damaged
      sample. The VIQ-PIQ differences of 260 neurologically impaired patients was
      compared to the WAIS-R standardization sample. The average VIQ-PIQ discrepancy of
      the patients was significantly larger than the mean IQ difference for normals.
      Comparison of the number of subjects whose VIQ-PIQ discrepancy equaled or
      exceeded 95% of the controls revealed no differences for the total sample and for
      individuals with low average or average intelligence. Conversely, the frequency
      of abnormal VIQ-PIQ differences was significantly greater among patients with
      Full Scale IQs <or= 79. The occurrence of an abnormal VIQ-PIQ discrepancy in
      persons with IQs <or= 79 should serve as a stimulus for further assessment.

PMID- 14589578
TI  - The New Adult Reading Test-Revised: accuracy in estimating WAIS-R IQ scores
      obtained 3.5 years earlier from normal older persons.
AB  - Scores on the New Adult Reading Test-Revised (NART-R) were used to estimate WA1S
      R IQ scores obtained approximately 3.5 years earlier from 54 normal older persons
      (M = 68 y; SD = 8.6). NART-R estimated IQ scores correlated reliably with earlier
      obtained IQ scores: FS1Q r = 0.70; VIQ r = 0.68; PIQ r = 0.61 (all p's < 0.05).
      NART-R estimated FSIQs underpredicted obtained FSIQs by an average of 3.8 points
      (SD = 9.3). The correlation between estimated and obtained FSIQ is fairly high
      and estimated FSIQ is reasonably close to obtained IQ, despite the considerable
      length of time passing between WAIS-R and NART-R administration. These results
      represent the first confirmation of the retrospective accuracy of the NART-R in
      estimating WAIS-R scores across time, a previously untested but critical
      assumption for clinical application of this approach. These results also
      apparently represent the first cross-validation of the NART-R in a sample of
      older Americans. These results suggest that further research on the clinical
      utility of the NART-R is warranted.

PMID- 14589580
TI  - Factor structure of the WAIS-R by educational level: an examination of elderly
      persons.
AB  - A factor analysis of the WAIS-R by educational level for persons 75 years and
      older was conducted. Two- and three-factor solutions were generated for persons
      with 0 to 11 years of education and for high school graduates. A two-factor
      solution composed of verbal and perceptual-organization factors best explained
      the WAIS-R scores for subjects with 11 or fewer years of education. However, a
      three-factor solution emerged for persons with 12 or more years of schooling and
      consisted of the verbal comprehension, perceptual-organization, and freedom from
      distractibility factors. Clinicians must be aware of the potentially different
      factor structures generated by educational level to provide the most accurate
      interpretation of WAIS-R scores for elderly persons.

PMID- 14589581
TI  - Neurobehavioral heterogeneity in schizophrenia.
AB  - Schizophrenia is a neurobehavioral disorder with heterogeneous symptomatology.
      Studies of cognitive function in schizophrenia have also demonstrated
      heterogeneous patterns and levels of function among patients. In this paper, we
      review attempts to arrive at meaningful subtypes of cognitive function in
      schizophrenia through the use of cluster analysis. The subtypes obtained were
      related to variables extrinsic and intrinsic to schizophrenia itself. It was
      noted that while classification of subjects was associated to some extent with
      extrinsic factors, such as age, education, and neurological comorbidity, a
      portion of the heterogeneity could still be associated with intrinsic factors. It
      was suggested that these factors might be consistent with currently proposed
      neurobiological subtypes of schizophrenia.

PMID- 14589582
TI  - Neuropsychological patterns of adolescents and young adults with spina bifida.
AB  - The purpose of this study was to examine neuropsychological profiles for patients
      with spina bifida. The sample consisted of 37 subjects with spina bifida between
      the ages of 14 and 23. Each of the subjects was seen individually and
      administered the Halstead-Reitan Neuropsychological Test Battery as well as the
      appropriate Wechsler Intelligence Scale. Scores from the Halstead-Reitan were
      subjected to cluster analysis to formulate clinical subtypes. The results
      indicated a three group solution was most appropriate, which appeared to reflect
      a continuum of dysfunction. Implications for rehabilitation programming are
      discussed.

PMID- 14589587
TI  - Empirical derivation and classification of subgroups of children with learning
      disorders at separate age levels.
AB  - This study classified subgroups of learning disabled (LD) children while
      considering the effects of age. Specifically, scores on the Halstead-Reitan
      Neuropsychological Battery (HRNB) for older children, the Wechsler Intelligence
      Scale for Children-Revised (WISC-R), and Wide Range Achievement Test (WRAT) were
      clustered for a large sample of public school LD children at the age levels 9-10,
      11-12, and 13-14 years old. Like clusters were then identified and collapsed
      across age groups. Discriminant analyses were performed at each age level, and
      for like clusters across ages as a measure of predictive validity. Results of
      this study suggested two distinct clusters at each age level; one showing diffuse
      deficits which varied little with age, and the other evidencing specific
      neuropsychological problems which may vary with age.

PMID- 14589588
TI  - Methodologic issues in neuropsychological research with HIV-spectrum disease.
AB  - Conflicting data have emerged from the initial studies of the neuropsychogical
      sequelae of human immunodeficiency virus (HIV) infection. This paper reviews key
      methodologic issues that must be addressed when embarking upon new research on
      the neuropsychology of HIV spectrum disease. Finally, suggestions are given for
      methodologic pitfalls to be avoided when conducting or interpreting research in
      this domain.

PMID- 14589589
TI  - The effect of ECT on the perception of emotion in depressed patients.
AB  - 35 psychiatric inpatients with diagnosed with unipolar or bipolar depression were
      given tests of memory, depression, and affective aprosody prior to the initiation
      of pulse unilateral nondominant ECT. Following ECT treatment, patients were given
      the same battery of tests using alternate forms of the same tests. The results of
      this study showed significant treatment effects in all three dependent variables
      without significant interaction between variables. The implications of these
      findings were discussed.

PMID- 14589590
TI  - Relationships among academic, neuropsychological, and intellectual status in
      subtypes of adults with learning disability.
AB  - A study was conducted of 102 adults with learning disability for the purposes of
      (1) contrasting a rule-based with an empirical method of classification into
      subtypes based on academic achievement levels in reading and arithmetic; and (2)
      examining cognitive profiles obtained with the Luria-Nebraska Neuropsychological
      Battery and the Wechsler Adult Intelligence Scale-Revised (WAIS-R) associated
      with each of the rule and empirically based subtypes. Both similarities and
      differences were found between classification methods. Both methods indicated
      that specific reading disability was associated with the most impaired cognitive
      profiles of the three subtypes identified. However, they did not agree concerning
      cognitive profiles of subtypes, characterised by a specific arithmetic deficit or
      a global deficit. It was found that both the Lurid-Nebraska and WAIS-R profiles
      distinguished among subtypes more by pattern than by level of performance.

PMID- 14589591
TI  - Longitudinal assessment of motor and sensory skills in academically disabled and
      control children.
AB  - Motor and tactile integration skills were sequentially assessed with academically
      average (N = 28) and academically disabled children (N = 17) over a 3-year
      period. The initial results demonstrated considerable differences between the
      groups. Analysis of variance and visual inspection of trends in the longitudinal
      data for the academically disabled group revealed a mixed pattern with catch-up
      in the motor areas and persistent delays in sensory areas. The results suggest
      different developmental patterns depending on the skill and group assessed. Right
      hand advantages were found across groups with motor speed whereas a left hand
      advantage was demonstrated on a stereognosis task. These right-left differences
      suggest an important developmental role for corpus callosum myelinization. The
      interpretation of soft neurological signs needs to be refined to allow for these
      sensory-motor, right-left parameters.

PMID- 14589593
TI  - How does the fable end? A reply to Hartlage.

PMID- 14589592
TI  - Traditional and computerized assessment procedures applied to the evaluation of
      memory change after temporal lobectomy.
AB  - After establishing that 40 temporal lobectomy patients (20 right, 20 left)
      demonstrated the same pattern of memory compromise as has been reported in prior
      studies, we examined the sensitivity of computerized tests of everyday memory
      skills to the cognitive change associated with temporal resection. Multiple
      cognitive deficits occur after left, but not after right, temporal lobectomies.
      Memory impairment after surgery is not limited to traditionally structured memory
      tests but is also evident on tasks designed to simulate activities of daily life.

PMID- 14589595
TI  - Human neuropsychology in the 1990s.
AB  - Predictions regarding research and service delivery in human neuropsychology
      during the 1990s are presented. Issues addressed include considerations regarding
      the following: developmental studies of "normal" brain-behavior relationships;
      simultaneous measurement of brain activity and behavior; dimensionality of
      psychometric instruments; statistics and mathematical models; socioemotional and
      personality correlates of brain disease; study of "at risk" groups;
      neuropsychological taxonomies; model and theory development; comparative
      neuropsychology; neurochemistry of brain-behavior relationships; impact of non
      neurological diseases; the interface of neuropsychology and psychiatry;
      applications in social problem areas; cognitive rehabilitation; and trends in
      certification and credentialing.

PMID- 14589596
TI  - Constructional praxis performance of Japanese and American, normal and brain
      damaged patients.
AB  - Numerous studies have suggested population differences between Japanese and
      Americans concerning various cognitive functions. Transcultural differences in
      spatial reasoning, language, and dominance for emotional expression raise
      important questions concerning current conceptions of hemispheric cerebral
      dominance for cognitive functioning. If cultural differences in cognition exist,
      learning may play a greater role in determining laleralizalion of cognitive
      functions than is presently accepted. To investigate these issues, we initiated
      two collaborative studies comparing Japanese with American normals and brain
      damaged patients on the Three-Dimensional Constructional Praxis Test. In normal
      subjects, there were no significant differences between the two cultures in the
      distribution of visuoconstructive ability. In patients with brain damage, the
      effects of unilateral brain lesions and their neuropsychological consequences on
      visuoconstructive ability were similar in both cultures. Thus, there are no
      apparent differences between the Japanese and American peoples in
      visuoconstructive abilities, or in the underlying cerebral organization of skills
      required to execute these functions.

PMID- 14589597
TI  - Comparison of two short forms of the Wisconsin Card Sorting Test.
AB  - Two short forms of the Wisconsin Card Sorting Test (WCST) were evaluated. The
      WCST-64 consists of one deck of 64 cards; derived measures are number of
      categories obtained and number of perseverative responses. The WCST-3 includes
      measures of the number of cards required to complete three categories and the
      number of perseverative responses. WCST protocols from 37 schizophrenics, 20
      temporal lobe epileptics, 11 patients with probable SDAT, and 54 normal controls,
      were scored using the three methods. Pearson correlations between WCST and WCST
      64 scores ranged from.70 to.91. while correlations between WCST and WCST-3 were
      somewhat lower (.36 to.82). The WCST-64 was superior to the WCST-3 in agreement
      with the full WCST. The WCST-3 tended to underestimate the number of
      perseverative responses on the full WCST. Although the use of a short form
      reduces reliability, the WCST-64 appears to be an acceptable alternative when
      administration of the full WCST is not possible.

PMID- 14589598
TI  - Treating a case of surface dyslexia after closed head injury.
AB  - We describe an original treatment program for surface dyslexia in a patient with
      a closed head injury. Addressing the question of whether the deficient lexical
      reading routes could be improved in this type of case. we designed three tasks
      and administered them over ten consecutive treatment sessions. Results indicate
      improved accuracy of responses as a function of presentation times or response
      times, or both, on all treatment tasks. Comparisons of standardized reading
      comprehension and oral reading tests before and after therapy disclosed increases
      in reading rate, with the patient's originally high level of accuracy remaining
      constant. This suggests that the patient incorporated the more rapid lexical
      reading strategy without compromising her level of accuracy.

PMID- 14589599
TI  - Changes in cognitive functioning associated with normal aging.
AB  - The present study explores age-related changes in cognitive functioning in a
      cohort of 122 healthy elderly volunteer subjects over a 3-year period. The sample
      was partitioned into four age groups: 57-65, 66-70, 71-75, 76-85 years. The
      results suggested high stability of factor structure over three testing probes,
      as well as selective attrition effect with significantly lower performance in
      those subjects, who dropped out from the study on the tests of verbal memory and
      mental speed. The results of repeated measures MANOVA on raw scores and
      univariate ANOVAs on factor scores comparing four age groups at each testing
      probe revealed a differential pattern of changes in verbal and nonverbal
      perception/memory versus mental speed/mental flexibility. Implications of these
      findings in clinical diagnostics were considered.

PMID- 14589600
TI  - Wechsler Verbal-Performance IQ discrepancies among psychiatric inpatients:
      implications for subtle neuropsychological dysfunctioning.
AB  - One hundred seventy-nine psychiatric inpatients were administered the WAIS-R and
      several neuropsychological and academic achievement tests. All subjects were
      assigned to three groups based on their WAIS-R's VIQ-PIQ discrepancy scores: (i)
      Low Verbal (Verbal IQ < Performance IQ. by at least 13 points); (ii) Low
      Performance (Performance IQ < Verbal IQ by at least 13 points); and (iii) Equal
      (Verbal IQ-Performance IQ within 13 points). The Low Verbal group made
      significantly more errors on the Speech Sounds Perception Test, demonstrated
      lower spelling scores, evinced more aphasic signs, and had had more special
      education placements than did the Equal or Low Performance groups. The Low
      Performance subjects demonstrated significantly more signs of constructional
      dyspraxia and performed more poorly on the Grooved Pegboard test. The
      neuropsychiatric patients who had Verbal-Performance IQ discrepancies of at least
      one standard deviation may be at risk for specific, subtle neuropsychological
      deficits.

PMID- 14589601
TI  - Neuropsychological assessment in public psychiatric hospitals: the changing state
      of the practice-1979 to 1989.
AB  - A ten-year follow-up survey of clinicians in publicly funded adult psychiatric
      hospitals throughout the United States was conducted to assess changes and trends
      in the practice of clinical neuropsychology. An 85% response rate was achieved.
      The survey produced data on the type and number of neuropsychological testing
      instruments in use, the type of training received by clinicians performing
      neuropsychological assessments, the psychiatric patient load and proportion of
      referrals which involve neuropsychological questions, the proportion of
      institutions employing psychologists with primarily neuropsychological duties,
      and the perceived efficacy of neuropsychological assessment techniques for
      discriminating functional from organic disorders. The findings indicate an
      increase in the level and variety of training as well as in the number of
      neuropsychological specialists in the field. However, levels of staffing appear
      to remain below service needs. Additional findings indicate the continued
      popularity of a small number of neuropsychological test batteries, a marked
      increase in the variety of testing instruments in use, and a general sense of
      trust in the efficacy of neuropsychological assessment techniques. The
      implications of these findings for the future of applied human neuropsychology
      are discussed.

PMID- 14589602
TI  - The detection of faked deficits on the Rey Auditory Verbal Learning Test: the
      effect of serial position.
AB  - The ability of subjects to fake deficits on the Rey Auditory Verbal Learning Test
      (AVLT) was evaluated. Subjects were randomly assigned to one of two malingering
      groups - one with a financial incentive (N = 30) and one without (N = 28) - or a
      control group (C) (N = 28), and a group of closed head injury patients (CHI) (N =
      18) was matched on age, sex, and education level. The two malingering groups did
      not differ significantly and were combined into a single malingering group (M) (N
      = 57). There was a significant serial position (the pattern of "recency" and
      "primacy" effects in recall) by group interaction effect, which may be the most
      promising indicator of deliberate distortion. When only level of performance was
      examined, the M group could fake believable deficits, but when the serial
      position effect was examined, it revealed that this was accomplished by
      suppression of recall from the first third of the word list (reducing the
      "primacy effect"), a recall pattern which did not occur in either the C or CHI
      group and may be an indication of malingering.

PMID- 14589603
TI  - Transcortical motor aprosodia: functional and anatomical correlates.
AB  - Transcortical motor aprosodia (TMA), one of eight hypothesized disorders of
      affective communication, is characterized by impaired production of affective
      prosody and facial gestures, with intact imitation and comprehension of affect.
      It has been proposed that cortical TMA arises from lesions in the superior or
      anterior lateral surface of the right frontal lobe, but for various reasons it
      has not been possible to fully test this proposal. There have been few cases of
      TMA reported, and lesions have been too diffuse to permit accurate localization.
      A case is presented that meets both the functional and anatomical criteria
      proposed for cortical TMA, thus providing support for this system of classifying
      disorders of effective communication. Results suggest that the prosodic and
      gestural deficits in TMA may be dissociated, and that the gestural component
      extends to nonaffective facial movements.

PMID- 14589605
TI  - Utility of the Luria-Nebraska Neuropsychological Battery-Children's Revision in
      the evaluation of reading disabled children.
AB  - The Luria-Nebraska Neuropsychological Battery-Children's Revision (LNNBCR) was
      used to investigate differences between reading disabled (RD) and academically
      normal children. The groups of 32 subjects each were equivalent with regard to
      age, sex, race, IQ, and SES of primary wage earner in the family. RD subjects,
      all of whom had been identified as learning disabled by the school, were
      moderately to severely impaired in reading, but not in math. Performance of the
      groups was significantly different on the battery as a whole and on an
      abbreviated form of the battery which excluded scales composed of items measuring
      language, reading, and arithmetic. With the abbreviated battery, the largest
      group differences were found on the Rhythm scale. It is hypothesized that poor
      performance on the Rhythm scale may reflect impaired auditory processing, which
      has a negative impact on the development of basic skills required for reading. A
      stepwise discriminant function analysis using the abbreviated battery correctly
      identified 84% of subjects. Evidence supporting discriminative validity of two
      methods of identifying RD children was found. Performance on an Experimental
      scale composed of nonreading items presumed to assess the integrity of areas of
      the brain mediating basic reading skills was no worse than on an equivalent
      randomly selected pool of items. The LNNB-CR may be a potentially valuable
      instrument for investigating neuropsychological differences between RD and normal
      children in that it provides relevant information to educators who must formulate
      remediation programs for RD children.

PMID- 14589606
TI  - Longitudinal changes in regional cerebral blood flow in a normal elderly group.
AB  - Only one published study to date has examined longitudinal age-changes in
      regional cerebral blood flow (rCBF) in an elderly group. It found rCBF declined
      significantly in their elderly sample over a 24 to 42 month period. The current
      study attempts to cross-validate the earlier study's findings with an older
      normal elderly group and a longer time interval between rCBF studies. This study
      is consistent with that investigation. The normal elderly did exhibit significant
      declines in blood flow across a variety of indices including: gray and white
      matter and the Initial Slope Index. These declines were generally on the order
      of.50 to.75 of a standard deviation loss. No significant differences in blood
      flow decline between males and females were discerned. While the young-old did
      exhibit greater blood flow than the old-old there were no significant differences
      in the rate of decline between the two age-groups.

PMID- 14589607
TI  - Memory retraining with adult male alcoholics.
AB  - The purpose of the present study was to evaluate the use of group memory
      retraining in adult male alcoholics. Subjects were 29 residents of a Salvation
      Army Adult Rehabilitation Center. Fourteen of the men volunteered to be in a
      memory retraining group and 15 to be in a control group, and all had memory
      functioning assessed during a pretest and again during a posttest eight weeks
      later. Memory retraining occurred in groups of three to six men who met one hour
      per week for eight weeks. Only one test improved significantly with memory
      retraining. Despite that fact, subjects appreciated the retraining and were more
      confident of their ability to learn and remember. Since alcoholics have many
      subjective complaints about memory dysfunction and previous research has
      demonstrated memory impairment, both a standardized clinically useful memory test
      battery and effective memory retraining techniques are needed.

PMID- 14589608
TI  - Clinical judgment and decision making in neuropsychology.
AB  - We review the literature on clinical judgment and statistical/actuarial
      prediction both in clinical psychology and in neuropsychology and we attempt to
      place these findings within the broader context of judgment theory. Current
      research on judgment in neuropsychology is consistent with research in other
      areas that documents the limitations of humans as judges and argues for increased
      utilization of actuarial methods and decision aids. In addition, there are
      virtually no data suggesting judgmental accuracy is related to experience,
      acknowledged expertise, or confidence in the accuracy of one's predictions. We
      attempt to identify judgment practices which contribute to diagnostic error in
      neuropsychology and we make recommendations that neuropsychologists can use to
      increase their judgmental accuracy. Research priorities in this area are
      discussed.

PMID- 14589609
TI  - Halstead-Reitan Neuropsychological Test performance of black, Hispanic, and white
      young adult males from poor academic backgrounds.
AB  - Forty-five black, Hispanic, and white young adult males of average range
      intellectual functioning, from poor academic backgrounds but with average
      academic achievement scores, were administered the Halstead-Reitan
      Neuropsychological Test Battery (HRNB). The results indicated that the Impairment
      Index, based on the traditional cutoffs, did not overly mis-represent this group
      as impaired. However, using the traditional cutoffs, the percentage in the
      impaired range on individual subtests ranged from 11% to 71%, suggesting caution
      when subtests are used apart from the battery (specifically, problems with the
      Finger Tapping test cutoffs are discussed). The three racial/ethnic groups did
      not have significantly different Impairment Indexes, and there were few
      significant differences between them on individual subtests.

PMID- 14589610
TI  - Block constructions of chronic alcoholic and unilateral brain-damaged patients: a
      test of the right hemisphere vulnerability hypothesis of alcoholism.
AB  - A detailed analysis of the block construction performance of chronic alcoholics,
      unilateral brain-damaged patients, and normal control subjects was conducted to
      test two hypotheses: (a) that alcoholics perform similarly to right-hemisphere
      damaged (RHD) patients but not left-hemisphere damaged (LHD) patients; and (b)
      that unilateral brain-damaged patients display qualitatively different strategies
      and errors. Differences in performance without a time limit and broken
      configuration errors suggest that the alcoholics have not incurred the type of
      visuospatial impairment characteristic of RHD patients. The LHD and RHD patients
      showed qualitative differences in their strategies and errors. Implications of
      the findings for research and clinical assessment of visuospatial dysfunction are
      discussed.

PMID- 14589611
TI  - Clinical assessment of tactile extinction: traditional double simultaneous
      stimulation versus quality extinction test.
AB  - The clinical assessment of tactile extinction is reviewed. The traditional or
      classical methods of double simultaneous stimulation (DSS) are
      compared/contrasted with the more recent Quality Extinction Test (QET). Various
      case studies are used to demonstrate the greater sensitivity of the QET over
      traditional DSS methods in detecting cerebral pathology. Clinical implications
      are discussed.

PMID- 14589613
TI  - Motor perseverations in schizophrenia.
AB  - Classical neuropsychological descriptions of prefrontal syndromes emphasize
      qualitative, productive symptoms, among which the phenomena known as motor
      perseverations occupy a central position. The now popular assertions that
      selective prefrontal dysfunction characterizes chronic schizophrenia would be
      more compelling if such productive symptoms could be reliably elicited in these
      patients. The present study demonstrated the presence of conspicuous motor
      perseverations in a sample of chronic schizophrenic inpatients, elicited using
      techniques that were developed and validated in studies of patients with known
      frontal lobe lesions. The observedperseverations closely resemble, both in
      severity and typology, those documented in cases with focal damage to prefrontal
      cortex. The findings support the contention that prefrontal dysfunction exists in
      chronic schizophrenia.

PMID- 14589614
TI  - Classification with the Luria-Nebraska neuropsychological battery: an application
      of cluster and ipsative profile analysis.
AB  - A sample of 114 subjects, 23 with predominantly left hemisphere brain damage, 25
      with predominantly right hemisphere brain damage, 26 with diffuse brain damage,
      and 40 with adult learning disability were administered the Luria-Nebraska
      Neuropsychological Battery (LNNB). The clinical scale data were cluster analyzed
      and subjected to an ipsative analysis of the cluster profiles. A four cluster
      solution was utilized. It was found that while stable clusters were produced,
      they were relatively unrelated to actual diagnoses. The first cluster had a
      normal mean profile, the second reflected specific language impairment, the
      third, nonverbal skill, memory, and intellectual impairment and the fourth,
      generalized impairment. The results were discussed in terms of the capacity of
      the LNNB to generate meaningful neuropsychological profiles.

PMID- 14589615
TI  - Treatment assessment of learning disabled children: is there a role for
      frequently repeated neuropsychological testing?
AB  - Test/retest practice effects among learning disabled (LD) and non-learning
      disabled (NLD) children were examined using the Halstead Category Test. Two
      experimental paradigms were performed. The first compared subjects on successive
      trials. The second paradigm used a control group to compare second trial
      performance of the experimental group with first trial performance of the
      controls. Both paradigms provide evidence of the relative inability of LD
      children to profit from practice. It is suggested that neuropsychological data
      can be used for short term test/retest as one indication of the efficacy of
      treatment intervention for learning disabled children without the practice effect
      being a significantly confounding variable.

PMID- 14589616
TI  - Characterization of cognitive functioning in a subgroup of children with
      congenital HIV infection.
AB  - The cognitive status of 12 clinically stable children with congenital HIV
      infection, nine of whom were neurologically impaired, age three to nine years,
      was assessed using the Kaufman ABC test. Seven of the children had ARC; five were
      diagnosed as having AIDS. The same children were evaluated by standard neurologic
      examinations with Characterization of tone and fine motor functioning. Two were
      diagnosed as being mildly retarded; six were borderline; and four tested as being
      of average intelligence. Visual-spatial perceptual based functioning was found to
      be more impaired than were abstract reasoning and verbally mediated skills in six
      (50%) of the patients. This pattern of impaired information processing was found
      irrespective of overall cognitive status. On neurological and physiatric
      examination abnormal developmental histories were obtained, or poor fine motor
      coordination, abnormal tone and gait, and impaired rapidly alternating movements
      were found in 9 of the 12 subjects. These findings suggest selective impairment
      in distinct areas of neurologic and neuropsychological functioning during stable
      phases of HIV infection in a select group of children. These patterns appear to
      persist over time. They differ from the clustering of impaired skills seen in
      children of comparable socio-cultural backgrounds without HIV infection.
      Similarities in functioning are noted between this subgroup of children with AIDS
      and ARC and comparable groups with cerebral palsy.

PMID- 14589617
TI  - The efficacy of a neuropsychological symptom inventory in the differential
      diagnosis of neurological, depressed, and normal patients.
AB  - This study examined the efficacy of using a symptom inventory to discriminate
      between neurological, depressed, and normal patients. Symptoms such as
      hallucinations, numbness of extremities, balance problems, and a localized place
      on head sensitive to touch were identified as the best predictors of the
      neurologically impaired patients when compared to the depressed and normal
      groups. Similarly, sleep problems was the best predictor of the depressed group.
      Using a step-wise discriminant analysis, a total of 91% of the patients were
      correctly diagnosed on the basis of reported symptoms. These results were
      discussed in terms of the overlap in symptomology between the neurological and
      psychiatric groups and the relative efficiency of using a self-report measure in
      making differential diagnoses.

PMID- 14589618
TI  - An investigation of the test-retest reliability of the Stroop Color-Word Test
      across two intervals.
AB  - The Stroop Color- Word Test is frequently used in neuropsychological settings.
      However, there has been no rigorous evaluation of the test-retest reliability of
      the commercially available version of the Stroop. The present study investigated
      the test-retest reliability of the Stroop across two different time intervals. In
      addition, the standard error of prediction and the standard error of differences
      were computed, and applications of the results to the use of the Stroop to
      document change in cognitive rehabilitation are discussed.

PMID- 14589619
TI  - Longitudinal neuropsychological changes in a "normal" elderly group.
AB  - The need for age-related normative data on neuropsychological measures is clearly
      important. This longitudinal study examines a "normal" elderly group's
      performance on the Luria-Nebraska Neuropsychological Battery (LNNB) across four
      years. This report is based on the 59 "normal" elderly volunteers seen in an
      earlier cross-sectional aging study (MacInnes et al., 1983). The LNNB Clinical
      Scales exhibited few significant changes across the four year time period. The
      test-retest correlations of the LNNB Clinical Scales ranged from.32 to.81. Few
      differences between males and females were seen. Similarly, being in an older
      subgroup did not affect the rate of change on the LNNB scores. Although, health
      status changed very little over the four years, health status at Time 2 did
      significantly predict 16 of the 17 LNNB Clinical Scales at Time 2. In summary, we
      found the LNNB accurately identified the "normal" elderly as normal. Similarly,
      their performance on the LNNB exhibited little meaningful change across four
      years.

PMID- 14589620
TI  - A controlled study of processing of semantic and syntactic information in
      Alzheimer's disease.
AB  - Several previous studies have suggested a possible dissociation in the ability of
      patients with Alzheimer's Disease (AD) to utilize syntactic versus semantic
      information. This report describes a controlled experimental investigation of AD
      subjects' ability to process syntactic and semantic information. Thirteen mildly
      and moderately impaired AD patients were compared with 17 age- and education
      matched elderly controls. Two tasks required subjects to identify and correct
      sentential errors; a third was a homophone spelling task. Results of the first
      task indicated that AD subjects were equivalent to controls in their ability to
      detect various types of sentential errors. When performing the second task, AD
      subjects were impaired in their ability to correct both types of errors, although
      there was a tendency for better performance with syntactically-based corrections.
      The third (homophone-spelling) task did not reveal a statistically significant
      differential sensitivity of AD subjects to syntactic versus semantic information.
      However, there was again a tendency for the former to be more easily processed.
      Results are discussed in terms of possible mechanisms which may underlie
      variations in the language-related performance of AD subjects.

PMID- 14589621
TI  - The clinical significance of cerebral atrophy in traumatic brain injury.
AB  - The neuropsychological effects of traumatic brain injury (TBI) as they relate to
      the chronic neuropathological chang.es of cortical atrophy and ventricular
      enlargement are reviewed. Computerized tomography (CT) and magnetic resonance
      imaging (MRI) methods are excellent at detecting many of these changes and
      results from these diagnostic methods should be incorporated in the
      interpretation of neuropsychological outcome in TBI patients. Several Clinical
      guidelines are presented on the relationship between TBI induced atrophy and
      neurobehavioral outcome.

PMID- 14589623
TI  - Test-retest reliability of a new form of the auditory verbal learning test
      (AVLT).
AB  - The equivalence between the original form (Form 1) of the Auditory Verbal
      Learning Test (AVLT), and a new form (Form 4) was examined in 51 normal adult
      subjects (20-67 years) of average estimated intelligence who were assessed in two
      separate sessions. Performance on the new form was equivalent to that on the
      original and most measures on the two tests showed significant positive
      correlations. Test-retest reliability of AVLT scores between sessions was also
      assessed, both globally and separately for Form 1 followed by Form 4 and for the
      reverse order. The most reliable measures on the AVLT were the total number of
      words learned over the five learning trials, (r =.77), and performance on the
      retention trial of the learning list following the presentation and performance
      of the distractor list (r =.70). These measures are sufficiently robust for use
      in clinical serial assessments.

PMID- 14589624
TI  - Concurrent validity of the MAE visual naming test.
AB  - Deficient confrontation naming has been observed in a number of neurological
      illnesses, as well as in aphasia and normal aging. The Visual Naming Test (VNT)
      of the Multilingual Aphasia Examination (MAE) is a standardized measure of
      confrontation naming. One hundred patients, consecutively referred for
      neuropsychological evaluation, were administered the VNT, Boston Naming Test
      (BNT), and WAIS-R. Concurrent validity of the two confrontation naming measures
      was demonstrated by their high intertest agreement. Performance on the VNT was
      found to be related to a unique ability separate from general intellectual
      functioning. Suggestions regarding the clinical use of the VNT are discussed.

PMID- 14589625
TI  - The experience of grief in the head-injured adult.
AB  - The current study attempted to assess the grief process in head-injured adults
      and to compare this with the grief process of individuals bereaved due to the
      death of a loved one. In addition, because grief often produces difficulty with
      cognitive processes, it was hypothesized that bereaved individuals would
      demonstrate impaired performance on neuropsychological tests of memory,
      attention, and reasoning ability. Significant differences between head-injured
      and bereaved individuals were found on only one clinical scale of the Grief
      Experience Inventory largely supporting the idea that grief among these
      individuals is similar. While a trend suggestive of the second hypothesis was
      found on tests of cognition, the head-injured and bereaved subjects differed
      significantly on all such tests with the exception of the Wisconsin Card Sorting
      Test and specific subtests of the California Verbal Learning Test.

PMID- 14589626
TI  - Episodic memory deficits in Alzheimer's disease: a behaviorally anchored scale.
AB  - This research represents an investigation into a behaviorally anchored scale for
      assessment of episodic memory. The Episodic Memory Scale (EMS) was theoretically
      derived and developed for use in a professional office environment. Performances
      of patients diagnosed with dementia of the Alzheimer's Type (N = 17) were
      significantly worse (p <.002) on the EMS than a comparison group (N = 17) of
      patients with cognitive dysfunction not associated with Alzheimer's disease. The
      EMS was positively and significantly correlated with other measures of episodic
      memory and less so with a measure of semantic memory. The extent to which
      episodic and semantic memory deficits relate to caregiver functional assessment
      ratings was explored. Findings are discussed with respect to ecological validity
      of the EMS and implications for reality monitoring ability. Utility of measuring
      episodic memory processes for purposes of neuropsychological assessment and
      caregiver decision-making are also discussed.

PMID- 14589628
TI  - Personality and self-report of cognitive functioning.
AB  - We examined the relationship of trait personality dimensions (negative
      affectivity and positive affectivity) on self-report of cognitive functioning.
      Ninety-six subjects who were screened to be without evidence of psychiatric or
      neurologic disorder, and who had previously completed the Tellegen Differential
      Personality Questionnaire (mean interval = 2 years) were sent a self-report
      questionnaire of cognitive functioning (MASQ). As predicted, negative affectivity
      (NA) was more strongly related to self-appraisal of cognitive functioning than
      was positive affectivity (PA); subjects with higher NA scores acknowledged more
      cognitive difficulties. Negative affectivity was also a stronger predictor of
      cognitive self-report than was self-report of current sad mood state. The
      implications of these findings for the examination of self-appraisal and accuracy
      of self-report are discussed.

PMID- 14589627
TI  - Long-term neuropsychological sequelae of fever associated with amnesia.
AB  - It has been well established that high fever can cause substantial damage to the
      cerebellum and also cause multiple small vascular lesions in neocortex and
      subcortical white matter. Beyond acute effects, the neuropsychological sequelae
      of these latter cortical and subcortical lesions have not been studied. The
      investigation reported involved 36 VA patients with a history of serious febrile
      illness. The febrile illnesses of the pyrexic subjects did not cause febrile
      seizures and resulted from diseases that did not directly involve the brain
      (e.g., encephalitis, meningitis, malaria). Control subjects were combat veterans
      who had suffered gunshot wounds, but who had no history of febrile illness.
      Pyrexic patients performed worse than controls on a variety of measures including
      language, memory, concentration, and word finding as well as failing a test of
      dichotic listening for words. Results demonstrate that hyperpyrexia can have
      lasting neuropsychological sequelae, and suggest that history of serious febrile
      illness be considered as an exclusionary criterion for participation in
      neuropsychological research concerning other topics or disorders.

PMID- 14589631
TI  - The orbitomedial frontal syndrome.
AB  - An orbitomedial frontal syndrome is proposed, characterized by anosmia, amnesia
      with confabulation, Go-NoGo deficits, personality change, and hypersensitivity to
      pain. The orbitomedial frontal syndrome is distinct from the clinical picture
      that results from dorsolateral frontal damage. Aspects of orbitomedial damage
      have been discussed previously in isolation, but we argue that recognition of
      this syndrome in toto is clinically important. It appears to be associated with
      poor social and vocational adjustment after brain injury, and the co-occurrence
      of features of the syndrome provides clues to underlying mechanisms for
      disinhibition and confabulation in frontal lobe patients.

PMID- 14589632
TI  - Neuropsychological complaint base rates of 170 personal injury claimants.
AB  - Reports base rate data for 50 controls and 170 personal injury claimants' self
      reported symptoms associated with neuropsychological impairment. These base rates
      were obtained from claimants with no history of brain injury or toxic exposure
      and no documented neuropsychological impairments. Personal injury claimants
      reported high rates of complaints generally recognized as being associated with
      neuropsychological impairment. For example, 93% reported anxiety or nervousness,
      92% sleeping problems, 89% depression, 88% headaches, 79% fatigue, 78%
      concentration problems, 77% irritability, 65% impatience, 61% feeling
      disorganized, 59% confusion, 56% loss of efficiency with everyday tasks, 53%
      memory problems, 44% dizziness, 39% numbness, and 34% word finding problems.
      These results underscore the need for caution when relying, on self-reported
      symptoms as evidence of brain damage in patients involved in litigation.

PMID- 14589635
TI  - Total amount learned versus learning rate of verbal and nonverbal information, in
      differentiating left-from right-brain injured patients.
AB  - Twenty Left-Brain Damaged (LBD), 20 Right-Brain Damaged (RBD), and 20 control
      subjects were compared on three different learning tasks: (a) verbal, the Paired
      Associate Learning subtest of the Wechsler Memory Scale; (b) figural, the Gollin
      Incomplete Figures task, which can be easily verbalized, and (c) spatial, the
      Stylus Maze. When learning ability was measured, by assessing the total amount
      learned (sum of items learned in all trials), the results showed that, on all
      three tasks, the control group's performance significantly surpassed that of the
      patient groups. The RBD group performed better than the LBD group on the verbal
      learning task, while LBD subjects performed better than their RBD counterparts on
      the spatial learning task. No significant difference between the two patient
      groups was detected on the figural task, suggesting that a task using visually
      and verbally codable stimuli is not useful in differentiating between LBD and RBD
      groups. When the learning rate was measured, similar results were obtained in the
      verbal and figural task. However, in the spatial task, the learning rates of the
      three groups did not significantly differ, probably because the specific task
      used required procedural learning, which is normally preserved in amnesics.

PMID- 14589636
TI  - General and specific cognitive dysfunctions in patients with Alzheimer's disease.
AB  - The purpose of the present study was to investigate the effect of Alzheimer's
      disease (AD) on general and specific neuropsychological function. Thirty-five
      subjects diagnosed with AD were compared to 30 medically normal aging control
      subjects using measures from the Halstead-Reitan Battery (HRB). All AD subjects
      were classified as "probable" AD (NINCDS-ADRDA) and found to be in the "late
      confusional" to "early dementia" stages of the disease (Global Deterioration
      Scale, GDS = 4-5). The AD group performed significantly worse than the controls
      on all measures of general neuropsychological function and almost all measures of
      specific functions. However, no differences were found between groups on motor
      abilities or many simple sensory functions. The findings demonstrate dramatic
      brain-behavior changes involving both general and specific cognitive functions
      which go beyond memory dysfunction even in the earlier stages of the disease. The
      neuropsychological pattern found may be the basis of a useful clinical-behavioral
      AD pattern in the earlier stages of the disease.

PMID- 14589637
TI  - Generalizability of two methods of estimating premorbid intelligence in the
      elderly.
AB  - Two methods for estimating premorbid WAIS-R IQ (Barona Reynolds & Chastain, 1984;
      Barona & Chastain, 1986) were compared in a sample of normal elderly and a sample
      of neurologically impaired persons. The normals consisted of 75 males with a mean
      age of 80.48 (SD = 4.57) years and the neurological group consisted of 20 males
      averaging 78.65 (SD = 5.62) years of age. For the normals, the percent of
      obtained IQs that fell within one standard error of estimate of the formula
      estimated IQs demonstrated adequate agreement of both methods for the Full Scale
      IQ, but relatively poor prediction for the Performance Scale. The Verbal IQ was
      adequately predicted by the 1984 method, but not the 1986 procedure. As expected,
      both estimation procedures overestimated the obtained IQs of the brain-damaged
      subjects.

PMID- 14589638
TI  - Quantitative and qualitative aspects of memory performance after minor head
      injury.
AB  - Neuropsychological investigation of minor head injury (MHI) has consistently
      corroborated patient subjective complaints of memory loss. An experimental group
      of 11 minor head-injured patients and a control group of age-matched normal
      volunteers were compared on the California Verbal Learning Test (CVLT) and on the
      Rey-Osterreith complex figure. Minor head-injured subjects were found to be
      impaired on measures of short-term and delayed free recall as well as on measures
      of organizational-semantic strategy in the retrieval phase. These findings are
      consistent with subjective reports from the patients and may in part explain
      reduced psychosocial and vocational adaptation following minor head injury.

PMID- 14589639
TI  - Malingering detected by forced choice testing of memory and tactile sensation: a
      case report.
AB  - A man with a possible diagnosis of multiple sclerosis was evaluated in connection
      with his claim for Social Security Disability. Two neurological examinations had
      revealed essentially normal findings. Neuropsychological testing revealed
      moderately severe deficits, but testing of his motivation with two forced choice
      measures, the Portland Digit Recognition Test and a finger graphesthesia
      procedure, both yielded performances significantly worse than chance. It was
      concluded that the patient was faking some or all of his deficits, and that his
      abilities had not been measured accurately. Forced choice testing is a robust
      procedure for documenting poor motivation.

PMID- 14589640
TI  - Factor analysis of the Wechsler Memory Scale and the Warrington Recognition
      Memory Test.
AB  - Subjects were 156 individuals referred, for psychological and neuropsychological
      evaluation. The Wechsler Memory Scale (WMS) including the 12h delayed condition
      of Russell's revision and Warrington's Recognition Memory Test (RMT) were
      administered as part of each evaluation. Using scores from the RMT subtests: (1)
      Memory for Words and (2) Memory for Faces, and scores from the WMS subtests: (3)
      Logical Memory, (4) Digit Span, (5) Visual Reproduction, and (6) Associate
      Learning flow associate pairs only), a principal components factor analysis was
      carried out with an orthogonal varimax rotation yielding four factors: (1) verbal
      learning and memory, (2) Figurai memory, (3) Recognition memory, and (4)
      Attention-Concentration. Results are discussed with respect to the independent,
      but complementary information provided by the WMS and RMT for measurement of
      memory functions.

PMID- 14589641
TI  - Fluidity theory and neuropsychological impairment in alcoholism.
AB  - In order to determine whether the "classic" alcoholic WAIS pattern is the result
      of right hemisphere damage or the loss of fluid intelligence abilities, right
      hemisphere damaged, left-hemisphere damaged, alcoholic, and control groups of 40
      subjects each were matched on the variables of age and education. They were
      administered the WAIS-Revised (WAIS-R) and four sensory and motor measures that
      were sensitive to lateralized damage but not to fluidity. The alcoholic group
      showed the "classic" pattern of a lower performance than verbal WAIS IQ. Although
      the left hand scores on the sensory and motor tests were significantly more
      impaired than the right hand scores for the right-hemisphere damaged group they
      were not for the alcoholic group. These results did not support the right
      hemisphere theory. Rather, as indicated by further analysis, the pattern is most
      adequately explained by the fluidity theory.

PMID- 14589642
TI  - Accuracy in neurohistory: David versus the giant.

PMID- 14589643
TI  - Impaired verbal and figural fluency after head injury.
AB  - Previous research has found that verbal fluency is reduced in head-injured
      patients and in patients with focal damage to the frontal lobes. The present
      study compares a task of verbal associative fluency with a new measure of
      nonverbal, or figural, fluency that focuses on speed of producing unique designs
      and accounting for perseverative tendencies. Using results from 35 head-injured
      patients and 50 normals, we found that both verbal and figural fluency are
      compromised following brain trauma. Consistent with previous research, patients
      with severe head injuries were more impaired than patients with moderate head
      injuries. The discussion focuses on those cognitive factors that might influence
      verbal or figural fluency.

PMID- 14589644
TI  - Family observations of everyday cognitive impairment in dementia.
AB  - The observations made by family members of cognitive impairment and decline serve
      an important role in the description of dementia-related illnesses such as
      Alzheimer's disease. A common clinical practice is to interview the family and
      informally gather information about the severity and history of intellectual
      impairment such as memory disorder and aphasia. The present study introduces a
      method to formalize this information gathering using an inventory that allows a
      family member to rate the presence and severity of the everyday manifestations of
      dementia. Results of initial psychometric studies of the rating scale indicate
      that a family member can make reliable judgments of everyday cognitive
      impairment. Observer ratings such as these should significantly enhance
      diagnostic efforts when they are used in conjunction with neuropsychological
      tests and in cases in which the demented person cannot participate in a full
      neuropsychological evaluation.

PMID- 14589645
TI  - Neuropsychological reference groups for 9- through 14-year-old subjects with
      identified learning disabilities.
AB  - The neuropsychological reference groups reported in this study are based on a
      sample of 1,325 learning-disabled subjects aged 9 through 14 drawn from a midsize
      midwestern metropolitan community. The sample was composed of 1,006 males and 319
      females. Separate means and standard deviations, reported for each gender and age
      group, were generated for 31 measures ordinarily included as part of the Halstead
      Neuropsychological Test Battery for Children. Several comparisons were made with
      other norms previously reported. The need for additional neuropsychological
      reference groups for children is discussed.

PMID- 14589646
TI  - Clinical acumen but psychometric naivete in neuropsychological assessment of
      educational disorders.
AB  - Many advances in clinical neuropsychology have resulted from the excellent
      clinical, observational skills developed in the field. In the development of
      assessment tools for clinical practice, advances in the field have not paralleled
      advances in applied psychometrics, especially in the assessment of educationally
      handicapped children. The Boder Test of Reading Spelling Patterns is examined as
      a detailed example of outstanding clinical acumen leading to a valuable heuristic
      that failed when translated into a practical assessment tool, primarily due to a
      lack of attention to the psychometric aspects of the scale. Implications of the
      failure to apply modern psychometric standards to test development in clinical
      neuropsychology are discussed.

PMID- 14589647
TI  - Neurodevelopmental and racial differences in tactile-visual (cross-modal)
      discrimination in normal black and white children.
AB  - Controversy exists as to when those functions associated with the left tertiary
      cortex become fully developed in children. To address this issue,
      neuropsychological development of tactile-visual (cross-modal) discrimination was
      assessed in 200 normal children aged 5 through 9 years. The factors of gender and
      race (black, white) were evaluated across this age span. A three-factor ANOVA
      revealed no gender differences, but significant main effects for age and race
      existed. There were no significant interactions. White children outperformed
      black children across all ages, and Sheffe's post-hoc comparisons revealed that,
      by age 7, children have mastered those basic cross-modal functions necessary for
      complex higher cognitive processes. The implications of these findings are
      discussed.

PMID- 14589648
TI  - Factor structure of Benton's tests of visual retention, visual construction, and
      visual form discrimination.
AB  - The standard drawing and multiple-choice versions of the Benton Visual Retention
      Test (BVRT), the Visual Form Discrimination Test (VFDT), the Rey Auditory Verbal
      Learning Test (AVLT), and the Wechsler Adult Intelligence Scale-Revised Digit
      Span subtest were administered to a mixed sample of 97 psychiatric, neurologic,
      and control subjects. Factor analysis of the Benton test battery measures alone
      showed that the standard and multiple-choice BVRT protocols performed very
      similarly. Scoring of the standard BVRT for errors and number of correct items
      was shown to be statistically redundant for this sample. Possible simplification
      of standard BVRT scoring was suggested. Copying and immediate visual-memory
      skills emerged as separable factors on the standard BVRT. When the AVLT and Digit
      Span measures were factor analyzed with the Benton lest battery measures,
      however, simple factorial structure emerged only for the AVLT measures (one
      factor) and the BVRT copying measures that were grouped with the VFDT. A verbal
      mediation component was thought to be associated with the multifactorial BVRT and
      multiple-choice BVRT results in this analysis.

PMID- 14589649
TI  - Relationship between the "cognitive triad" from the personality inventory for
      children and an extended Halstead-Reitan neuropsychological battery.
AB  - The relationships between the Achievement, Intellectual Screening, and
      Development scales from the Personality Inventory for Children (PIC) and a
      comprehensive neuropsychological battery were examined in a sample of 49 children
      with histories of behavioral problems, learning problems, or both but without
      known neurological impairments or pervasive developmental disorders. Using
      stepwise multiple regression, the PIC scales predicted global neuropsychological
      functions moderately well, particularly verbal IQ and achievement. More specific
      neuropsychological functions were not significantly predicted. The Developmental
      scale from the PIC consistently outperformed the other two PIC "cognitive-triad"
      scales, and the latter made no statistically significant additional contribution
      in predicting neuropsychological functions after the contribution of the
      Development scale was taken into account.

PMID- 14589650
TI  - Rapid recovery from crossed aphasia in a dextral.
AB  - A case of crossed aphasia in a right-handed woman resulting from a right
      hemisphere stroke is reported. Rapid recovery occurred between an initial
      evaluation performed at one month poststroke and a follow-up evaluation performed
      at 2 months post. The cerebral organization and the relationship between language
      and other cognitive abilities in crossed aphasics are discussed. Additionally,
      the unitary and transient models of crossed aphasia are examined.

PMID- 14589651
TI  - Response time as a dependent measure on the Category Test of the Halstead-Reitan
      Neuropsychological test Battery.
AB  - The role of response time on the Category Test of the Halstead-Reitan
      Neuropsychological Battery (HRNB) was examined. Seventy-two normal adult
      volunteers were administered the complete HRNB. Average response times for
      individual slides were computed for correct (CRT), incorrect (IRT), and total
      (TRT) scores on the Category Test. The utility of these response-time scores was
      examined in the context of other HRNB variables seen to be factorially related to
      the Category Test. Results from a stepwise multiple regression analysis indicated
      that approximately 15% of the variability in Category error scores was explained
      by a measure of spatial memory (TPT-location), and an additional 15% was
      accounted for by response time (TRT and IRT). A factor analysis indicated that
      the three measures of response time loaded on a factor that accounted for 21% of
      the explained variability in HRNB performance.

PMID- 14589652
TI  - The subacute effects of CNS prophylaxis for acute lymphoblastic leukemia on
      neuropsychological performance: a comparison of four protocols.
AB  - We report an assessment of the intellectual functioning after one year of therapy
      of 117 children treated for acute lymphoblastic leukemia (ALL) who were assigned
      to one of four protocols for central nervous systems (CNS) prophylaxis. These
      protocols were (a) 2400 rad cranial irradiation plus concurrent intrathecal
      methotrexate (i.t. MTX), (b)i.t. MTX alone, (c) 1800 rad cranial irradiation plus
      concurrent i.t. MTX, and (d) a protocol for high-risk patients that included
      intensive systemic chemotherapy plus 2400 rad delayed irradiation.
      Neuropsychological evaluation consisted of the Wechsler intelligence scales, the
      Wide Range Achievement Test, and selected tests from the Halstead-Reitan
      Neuropsychological Battery administered one year after diagnosis. All patients
      performed in the average range on measures, although the high-risk patients
      performed marginally worse than did the others. In general, our results do not
      support previous reports that cranial irradiation results in early adverse
      neuropsychological sequelae.

PMID- 14589653
TI  - Neurobehavioral and neurodiagnostic aspects of late-onset psychosis.
AB  - The onset of psychotic symptoms later in life requires careful multidisciplinary
      evaluation, yet may pose significant diagnostic difficulties given current
      classification schema. Here we describe a patient with new onset of schizophrenia
      like symptoms at age 61. Cognitive screening and laboratory tests were within
      normal limits. However, detailed neuropsychological studies suggested mild to
      moderate, diffuse cerebral dysfunction, and MR revealed an arachnoid cyst around
      the right sylvian fissure. Three annual follow-up evaluations demonstrated no
      additional cognitive deterioration. Neuropsychological findings are discussed
      along with limitations of current psychiatric nosology and cognitive screening
      tasks in older patients with new-onset psychosis.

PMID- 14589654
TI  - How much do 'attention' tests tell us?
AB  - Twelve measures commonly used to assess attentional processes were examined in a
      sample of 120 outpatients referred for neuropsychological evaluation. A single
      factor solution emerged. A second analysis partially replicated factors derived
      by Shum. McFarland, Bain, and Humphreys (1990). Classification rates (impaired
      vs. unimpaired) for the measures are presented. The implications of these
      findings for clinical assessment of attention are discussed

PMID- 14589655
TI  - Neural correlates of dementia: regional brain metabolism (FDG-PET) and the CERAD
      neuropsychological battery.
AB  - The present Investigation examined the biological correlates of the cognitive
      deficits of Alzheimer's disease and related dementias using the
      neuropsychological assessment battery of the Consortium to Establish a Registry
      of Alzheimer's Disease (CERAD) and positron emission tomography (PET). Resting
      state cerebral glucose metabolism was measured using the labelled radiotracer,
      [18F] Fluoro-2-deoxyglucose (FDG), in a sample of patients with mild to moderate
      dementia (n = 66). Specific and predictable relationships were seen between
      regional brain metabolism (left and right, frontal, temporal, and parietal lobes)
      and the neuropsychological measures of verbal fluency, constructional praxis, and
      verbal list learning. On tests of naming and delayed verbal recall only
      diminished FDG uptake in the left frontal lobe and the left temporal lobe,
      respectively, approached significance. This study demonstrates the expected
      relationships between neuropsychological performance and regional cerebral
      metabolism, thereby providing support for the CERAD battery as a valid measure in
      the clinical evaluation of dementia and for the use of FDG-PET in brain-behavior
      studies of dementia.

PMID- 14589656
TI  - Base rate and simulated symptoms of mild head injury among normals.
AB  - This study examined the vulnerability of several self-report instruments commonly
      used in neuropsychological evaluation - the Iowa Interview for Partial Seiwre
      Like Symptoms, Postconcussion Checklist (PCL). Postconcussion Syndrome Checklist
      (PCSC), and Beck Depression Inventory (BDI) - to exaggerated or feigned
      complaints. Two hundred twenty-nine college student volunteers completed the
      instruments under one of three conditions: I) Base Rate/Control; simulated Head
      Injured, but 2) without or 3) with prospect of financial gain for the injury.
      Although the simulated Head Injured groups did not differ significantly from one
      another, both groups endorsed more symptoms than the Base Rate group, suggesting
      that the instruments are vulnerable, to simulation. Base rates of head injury
      symptoms in the normal population, laypersons' knowledge about the sequelae of
      mild head injury, and implications of using symptom checklists in medicolegal
      evaluations were discussed, as was the desirability of replicating this study
      with noncollege student populations.

PMID- 14589657
TI  - Relative sensitivity of the WAIS-R subtests and selected HRNB measures to the
      effects of brain damage.
AB  - Reitan has argued that Halstead-Reitan Neuropsychological Battery measures are
      more sensitive to the effects of brain damage than are measures from the Wechsler
      intelligence scales. This proposal was investigated in groups of 65 brain-damaged
      subjects and 45 nonbrain-damaged controls equated for age and level of education
      and subgroups of 34 brain-damaged subjects and 34 nonbrain-damaged controls
      closely matched on age and WAIS-R full Scale IQ. Differences on Halstead-Reitan
      measures found in the larger groups were not found in the subgroups matched on
      age and IQ. Further, discriminant analyses showed that 11 Halstead-Reitan
      measures were equivalent to the 11 WAIS-R subtests in discriminating brain-damage
      and nonbrain-damaged subjects. Thus, the proposal for poorer sensitivity of the
      WAIS-R subtests was not supported.

PMID- 14589658
TI  - Application of a forced-choice memory procedure designed to detect experimental
      malingering.
AB  - The detection of dissimulated cognitive deficits is an important issue in many
      clinical assessment situations. Specific procedures designed to aid in this
      detection can be useful additions to standard assessment protocols. The present
      study investigates the potential utility of a modification of the forced-choice,
      symptom validity paradigm to the assessment of memory deficits. Previous research
      indicated that the procedure could discriminate between college students
      instructed to malinger memory impairment and college students instructed to
      perform at their best ability. The present study administered a forced-choice
      memory assessment instrument to 60 psychiatric patients, 60 normal community
      volunteers, and 60 neuropsychological patients. Thirty psychiatric patients and
      30 community volunteers were given instructions to malinger. Discriminant
      function analyses yielded an overall correct group classification rate of 90.6%,
      with 5% of the nonmalingering subjects and 18.3% of the experimental malingerers
      incorrectly classified.

PMID- 14589659
TI  - Rey figure distortions reflect nonverbal recall differences between right and
      left foci in unilateral temporal lobe epilepsy.
AB  - Recall of the Rey Complex Figure (RCF) by patients with left (N = 26) or right (N
      = 18) temporal lobe epilepsy was scored in terms of the qualitative approach
      developed by Loring, Lee, and Meador. Patients with right temporal lobe epilepsy
      exhibited significantly more qualitative errors on recall of the RCF than
      patients with left temporal foci, whereas standard RCF scores failed to
      differentiate the groups. A linear discriminant function analysis showed that 66%
      of patients were correctly classified into lateral focus groups on the basis of
      qualitative scores, with a sensitivity of 50% and specificity of 77%. Although
      unsuitable for clinical use in its present form, the qualitative approach appears
      to be a promising one. The findings offer support for the position that some
      aspects of nonverbal memory are critically dependent on the integrity of the
      right temporal lobe. The implications of this for reorganization of cerebral
      representation are examined.

PMID- 14589660
TI  - MMPI correlates of poststroke neurobehavioral deficits.
AB  - MMPI profiles of 130 male veterans with cerebrovascular accidents were examined
      in relation to type and degree of neuropsychological deficit, hemispheric
      location of lesion, and time poststroke. Three neurobehavioral factors (Verbal,
      Visuospatial, Sensorimotor) were extracted from the Halstead-Reitan Battery and
      Wechsler Memory Scale. Canonical analyses revealed verbal impairment to be
      associated with greater openness in reporting emotional difficulties (Scale F)
      and limited social facility (Scale Hy). Sensorimotor deficits were associated
      with anxiety and distress (Pt) in patients with left hemisphere (LHD) but not
      right hemisphere damage (RHD). Although RHD and LHD patients had similar
      composite MMPI profiles, neuropsychological deficits in RHD were unrelated to
      MMPI scores. Time poststroke was independent of MMPI findings in both LHD and RHD
      samples.

PMID- 14589661
TI  - Definitional issues and neurobiological foundations of selected severe
      neurodevelopmental disorders.
AB  - This article reviews current definitional issues, selected neuropsychological
      findings, and presumed neurobiological underpinnings of two of the more commonly
      identified severe neurodevelopmental disorders: mental retardation and autistic
      disorder. Although these disorders represent two of the more common severe
      neurodevelopmental disorders encountered by child neuropsychologists practicing
      in clinical and research settings, they have not received the amount of attention
      from the field of neuropsychology as other kinds of neurodevelopmental disorders.
      Although there are few definitional controversies surrounding these disorders,
      findings accrued to date reveal solid evidence for neurological processes
      underlying each of these disorders. In addition, each of these diagnoses likely
      represents a heterogeneous group of disorders, suggesting that a syndrome
      analysis approach would prove beneficial for increasing our understanding of each
      disorder. Conclusions are drawn for the clinician and researcher, particularly
      with respect to using a neuropsychological perspective and assessment strategies
      with children with more severe disorders.

PMID- 14589662
TI  - Neuropsychological sequelae of hard metal disease.
AB  - To evaluate the memory complaints of a group of patients with hard metal disease,
      12 adult, former tungsten carbide workers with hard metal disease and 26 healthy,
      unexposed control subjects matched for age, race, sex, occupational status and
      education were administered the Wechsler Memory Scale-Revised (WMS-R), the
      Peterson Word Triad Test, Squire's Current Events Test (including both the recall
      and recognition forms), and Squire's Television Title Recognition Test. The
      exposed group demonstrated deficits in short-term verbal memory, allocation of
      central processing resources, and remote verbal memory compared to the control
      group. Visual memory was spared. Comparisons were made to previous investigations
      of memory functioning within the toxicology literature.

PMID- 14589663
TI  - Neuropsychological test patterns in men for Alzheimer's and multi-infarct
      dementia.
AB  - This paper examined three patterns of test performance on the Halstead Reitan
      Battery (HRB) and the Wechsler Adult Intelligence Scale-Revised (WAIS-R),
      including Fuld's formula, that differentiated Alzheimer's Disease (AD) from
      cerebrovascular disease, especially Multi-Infarct Dementia (MID). Study 1 and 2
      utilized 12 AD subjects and 13 subjects who had transient ischemic attacks
      (TIAs). All of the subjects in this study were male. The severity of impairment
      was equated. A WAIS-R deterioration pattern was found for the AD subjects, from
      which a formula was derived that correctly identified 84% of the subjects. The
      Fuld formula identified 76%. In regard to the HRB, Motor tests especially were
      less impaired for AD subjects and the HRB formulas correctly identified about 92%
      of the subjects. A third study, using an entirely new sample, applied these
      formulas to 11 AD and 28 MID subjects. The same rate of separation for the HRB
      formulas was found. Neither the WAIS formula, with the original cutting points,
      nor did the Fuld formula quite reach significance.

PMID- 14589664
TI  - Patterns of memory dysfunction among children surviving temporal lobe tumors.
AB  - We compared the cognitive functioning of seven children with left and seven
      children with right temporal lobe tumors one year or more following completion of
      medical intervention (surgical resection + radiation therapy). No differences
      were found between the two groups with respect to verbal IQ, performance IQ.full
      scale IQ, verbal minus performance IQ, or verbal comprehension, perceptual
      organization, or freedom from distractability factor scores. After adjusting
      memory test results for variance attributable to general intelligence, three
      children with left and four children with right temporal tumors exhibited
      specific auditory-verbal memory dysfunction; five of these children had
      concurrent visual-verbal memory dysfunction. Children receiving radiation therapy
      to the tumor were at significantly greater risk for verbal memory problems.
      Reading and spelling achievement were significantly correlated with verbal memory
      performance. Inconsistent association between cerebral hemisphere of tumor and
      type of cognitive deficit may be related to the relatively slow progression of
      the tumor and regional interventions such as radiation therapy. Nevertheless, the
      results of the present report suggest that the majority of children diagnosed
      with temporal lobe tumors are at increased risk for memory dysfunction and
      academic failure.

PMID- 14589665
TI  - Early detection of fronto-temporal degeneration by clinical evaluation.
AB  - Although Alzheimer's Disease (AD) is the most common degenerative dementia, other
      neuropathological processes are well known to cause dementia syndromes. Fronto
      temporal degeneration (FTD) is one such entity, and often produces a clinical
      presentation distinct from that of AD. Some FTD cases are shown at autopsy to be
      classic Pick's Disease, but others defy precise classification at this point
      because they lack characteristic Pick bodies. We describe a case of putative FTD
      in a 54-year-old man with personality change and complete Kluver-Bucy syndrome.
      Neuropsychological evaluation disclosed evidence of extensive frontal system
      dysfunction, with lesser problems in memory, language, and visuospatial skills.
      Magnetic resonance imaging studies after 17 months of the illness were largely
      nonspecific, but a follow-up scan 16 months later revealed bifrontal and
      bitemporal atrophy with ventricular enlargement. Neuromorphometric analysis
      suggested an increase in cortical atrophy and ventricular dilation over time.
      This case emphasizes the value of careful clinical evaluation in unusual non-AD
      degenerative dementias and suggests that neuroimaging studies may be less
      sensitive in the early diagnosis of such cases.

PMID- 14589667
TI  - Alternatives to the Glasgow Coma Scale as a quality of life predictor following
      traumatic brain injury.
AB  - Conventional "staging " of traumatic brain injury (TBI) typically uses depth of
      coma assessed by the Glasgow Coma Scale (GCS) score near admission as a severity
      marker. Frequently, early GCS scores are contaminated by alcohol or drug
      ingestion and other, nonneurological organ system trauma. As well, this measure's
      usefulness is limited due to its restricted range in survivors. Here we explore
      the utility of using length of posttraumatic amnesia, coma duration, and age as
      indirect markers of severity. Cluster analytic techniques were used to examine
      the relationship of severity so defined to long-term outcome in 106 mild,
      moderate, and severe TBI patients. Results indicate complex relationships between
      cluster groups with the influence of age of patient being highlighted as an
      important moderator in determining severity of injury and later psychosocial
      outcome.

PMID- 14589668
TI  - Order effects in the administration of the Booklet Category Test and Wisconsin
      Card Sorting Test.
AB  - In order to evaluate the possibility of significant order effects, the Booklet
      Category Test and Wisconsin Card Sorting Test were administered in
      counterbalanced order to 20 psychiatric patients, 36 neurological patients, and
      30 healthy, elderly individuals. Administering the Booklet Category Test first
      improved scores on the Wisconsin Card Sorting Test, although not to a
      statistically significant degree. Unexpectedly administering the Wisconsin Card
      Sorting Test first resulted in poorer scores on the Booklet Category Test. The
      results are discussed in terms of future research and clinical implications.

PMID- 14589669
TI  - Seashore Rhythm test: comparison of Signal Detection Theory and standard scoring
      procedures.
AB  - The effects of age and instructional set on Seashore Rhythm test performance were
      examined with standard scoring and Signal Detection Theory (SDT) procedures.
      Neurologically intact young (17-28 years) and old (65-92 years) subjects were
      given standard test instructions with sentences added which stated that specific
      proportions of the test stimuli would be identical or different. Age differences
      in d' scores were highly correlated with standard Rhythm scores. While standard
      scores were unaffected by instructional set, all three SDT measures of response
      criteria detected effects of instructional set, or an age by instructional set
      interaction. SDT scoring of the Rhythm test yields a measure of auditory
      sensitivity comparable to standard methods and detects response bias on the lest
      that standard procedures cannot.

PMID- 14589670
TI  - Evaluation of two new neuropsychological tests designed to minimize cultural bias
      in the assessment of HIV-1 seropositive persons: a WHO study.
AB  - In the course of the preparatory work for the WHO cross-cultural study on the
      neuropsychiatric aspects of HIV-I infection, two new neuropsychological tests
      (the WHO/UCLA Auditory Verbal Learning Test and the Color Trails 1 & 2) were
      developed. The evaluation of these tests was performed at four sites, two in
      developed and two in developing countries. The data obtained suggest that the
      tests are more culture fair than others currently used to assess the same
      functional domains, that they are sensitive to HIV-1-associated cognitive
      impairment, and that this sensitivity "holds" across different cultures.

PMID- 14589671
TI  - The Rey AVLT recognition memory task measures motivational impairment after mild
      head trauma.
AB  - The effect of financial incentives on Rey AVLT recognition memory performance was
      assessed. Clinically referred mild head trauma (MHT) patients with financial
      incentives were compared to patients with neurologically documented brain
      dysfunction who did not have financial incentives. The MHT group was subdivided
      into a group with strong performance on a measure of motivation, the Portland
      Digit Recognition Test (PDRT), and a group with weak performance on the PDRT. The
      resulting three groups were equated on Rey AVLT acquisition, age, and education.
      The MHT subgroup with poor PDRT scores also was significantly impaired on
      recognition memory. In the total sample the prevalence of recognition scores of
      less than 6 correct was 27% in the MHT group and 5% in the brain dysfunction
      group. We conclude that severe Rey AVLT recognition memory impairment likely
      reflects motivation to exaggerate deficits, at least in MHT patients with no
      neurological evidence of brain injury.

PMID- 14589672
TI  - Distinguishing between depression and dementia in the elderly: a review of
      neuropsychological findings.
AB  - Distinguishing between cognitive deficits seen in depression and progressive
      dementing, diseases is complex and often difficult clinically. We review recent
      neuropsychological studies comparing normal elderly individuals, depressed
      patients, and patients with progressive dementias. Findings from these studies
      suggest that the distinction between depression and dementia is fairly
      straightforward and facilitated by neuropsychological evaluation. Data from
      neuroimaging studies of depressed elderly are reviewed and integrated with the
      neuropsychological findings. A descriptive scheme for categorizing elderly
      patients is proposed. It is suggested that the label "pseudodementia" be
      discarded in favor of more thorough description of cognitive deficits associated
      with various clinical presentations.

PMID- 14589673
TI  - Judgment of facial expression of emotion in unilateral brain-damaged patients.
AB  - Patients with unilateral brain damage and normal controls were asked to give (1)
      inter-emotion judgment within the photographs of six facial emotions in terms of
      mutual similarities, and (2) intra-emotion judgment within the hemifacial
      composite photographs of an emotion in terms of intensity of expression. Right
      brain-damaged patients could differentiate between the emotion of happiness and
      all other emotions. Left brain-damaged patients differentiated between aroused
      nonaroused emotions. Normal controls differentiated between positive-negative as
      well as aroused-nonaroused emotions. Left-left facial composites were judged to
      have expressed more intensely than right-right facial composites or normal/mirror
      reversed facial orientations of emotions (except fear) by any group (p >.05).

PMID- 14589674
TI  - Neuropsychological and socio-emotional correlates of specific-arithmetic
      disability.
AB  - Neuropsychological and socio-emotional factors associated with specific
      arithmetic disability were investigated in an unselected sample of New Zealand
      children. Subjects were 17 specific-arithmetic disabled, 27 specific-reading
      disabled, 63 generally disabled, and 50 nondisabled 13 year olds. Evidence was
      sought for an association between specific-arithmetic disability and the
      neuropsychological and socio-emotional correlates of Nonverbal Learning
      Disability syndrome (NLD). NLD is characterized by a pattern of nonverbal and
      verbal neuropsychological strengths and weaknesses, and appears to place
      individuals at greater risk for internalizing psychopathology, than other
      learning disabilities. Only specific-arithmetic disabled subjects were found to
      show a neuropsychological profile reminiscent of NLD. Evidence of poor socio
      emotional adjustment was found across all three learning-disabled groups, and was
      greatest among generally disabled subjects. We found that the specific-arithmetic
      disabled subjects exhibited the greatest degree of overlap between internalizing
      psychopathology and a NLD neuropsychological profile. The results are interpreted
      as providing some support for the idea that specific-arithmetic-disabled
      individuals may be at greater risk for the NLD syndrome than either generally
      disabled or specific-reading-disabled individuals.

PMID- 14589675
TI  - MMPI-2 interpretation of patients with cerebrovascular disease: a correction
      factor.
AB  - The validity of the conventional Minnesota Multiphasic Personality Inventory
      (MMPI) interpretation as applied to neurologic patients has been increasingly
      questioned on the grounds of the test's psychiatric normative base and inclusion
      of items that may be sensitive to bona fide neurologic symptoms. This study used
      110 patients with cerebrovascular disease (CVD) to (i) determine whether the 370
      item pool of the MMPI-2 (abbreviated form) contains a unitary neurologic symptom
      factor, and (ii) devise a systematic approach to correct for patient endorsement
      of such items. Commonly endorsed items that differentiated the CVD sample from a
      group of normal adults were factor analyzed. Bona fide neurologic complaints (21
      items) emerged as the major discriminative source of variance in the 370 MMPI-2
      item pool that tends to inflate estimates of psychopathology (Scales 1, 2, 3, and
      8), alter profile codes types, and potentially affect decision-making related to
      the diagnosis and treatment of CVD patients. Recommendations regarding a greater
      reliance upon content scales and the use of a corrective scoring key are
      discussed.

PMID- 14589676
TI  - The effects of unilateral and multifocal lesions on the WAIS-R: a factor analytic
      study of stroke patients.
AB  - An exploratory maximum likelihood factor analysis of the inter-correlations among
      the 11 subtests of the WAIS-R was undertaken for 167 patients who had a primary
      diagnoses of cerebrovascular accident (right hemisphere, n = 79; left hemisphere,
      n = 55; diffuse or multifocal, n = 33). On the WAIS-R, this sample performed
      below normative standards (average scaled score = 7.1), but demonstrated a
      pattern of variability among subtests similar to the normative groups.
      Interestingly, VIQ-PIQ discrepancy analyses revealed V > P profiles for patients
      with lesions in either or both hemispheres. The best fit for the WAIS-R matrix
      was an oblique two-factor model comprised of the Verbal and Performance subtests.
      This factor solution, which was moderately correlated (.52), accounted for 58.8%
      of the total variance. The stability of a two-factor structure in this neurologic
      impaired population suggests that the WAIS-R is a robust measure, even when used
      within such a rehabilitation population. Only two of the eleven subtests (i.e.,
      Comprehension and Picture Arrangement), however, were related to lesion site.
      Rehabilitation settings may need to rely more on neuropsychological procedures
      that measure the more "fluid" areas of neurocognitive ability, in contrast to the
      WAIS-R which appears less sensitive to the neurological impairment associated
      with stroke.

PMID- 14589677
TI  - Normative data on a self-rating scale for evaluating memory in everyday life.
AB  - Normative data are provided on 1,106 subjects who were administered a memory self
      rating scale. This scale includes 21 ability-to-remember items yielding 5
      factors, 24 items assessing frequency-of-occurrence of memory failures yielding
      five factors, and four global rating items assessing overall comparison to
      others, comparison to the best one's memory has been, speed of recall, and
      concern or worry over memory function. Test-retest reliabilities of the various
      self-rating factors exceeded .80. Research and clinical applications are
      discussed.

PMID- 14589678
TI  - A shortened intermediate version of the Halstead Category Test.
AB  - An effort was made to determine whether the intermediate (ages 9-14) version of
      the Halstead Category Test (HCT) could be shortened to increase clinical utility
      without altering it's basic psychometric properties. The Long Intermediate
      Halstead Category Test was administered to four clinical groups. Statistics were
      conducted to verify that these groups did not relate differentially to the
      Category Test or other neuropsychological measures. Twelve shortened Category
      Tests were then extracted. The psychometric properties of these extracted
      shortened versions were compared to the long version and the three best were
      selected for further tests. These three shortened versions were then cross
      validated. Results indicated that the psychometric properties were similar across
      the shortened versions. The shortest version was there for chosen which best
      retained the characteristics of the original test.

PMID- 14589679
TI  - Neuropsychological deficits in a case of H2S anoxic encephalopathy.
AB  - A comprehensive examination of the neuropsychological status of a young male
      patient of anoxic encephalopathy due to acute hydrogen sulfide intoxication was
      made. Agraphia, acalculia, deficits of associative verbal fluency and design
      fluency, and general intellectual deterioration were noted. Qualitative analysis
      of number operation revealed a specific impairment in the performance of
      division. Further analysis of graphic output showed a phonological substitution
      feature. The disorder of written language in the absence of disorders of language
      and communication in other modalities and praxis can be considered pure agraphia.
      The possible neural substrate for pure agraphia and partial acalculia was also
      discussed.

PMID- 14589680
TI  - Clinical differentiation of the attention deficit disorder subtypes: do
      sensorimotor deficits characterize children with ADD/WO?
AB  - Previous researchers found that children with Attention Deficit Disorder Without
      Hyperactivity (ADD/WO) tended to perform more poorly than children with Attention
      Deficit Disorder With Hyperactivity (ADD/H) on measures of motor and sensory
      functions. In the present study, a prototype sensorimotor soft sign battery was
      developed which limited cognitive involvement. It was hypothesized that ADD/WO
      children would exhibit a greater number of soft signs than ADD/H children who in
      turn would show more soft signs than normal children. Participants were 31
      children ranging in age from 72 to 144 months. The SNAP checklist (Pelham &
      Murphy, 1981) was used in arriving at an experimental diagnosis. No differences
      were found between the ADD/WO and normal groups. The ADD/H group exhibited more
      soft signs than the normal group at all ages and more than the ADD/WO group above
      96 months of age.

PMID- 14589681
TI  - Pesticide exposure and neuropsychological impairment in migrant farm workers.
AB  - The chronic, long-term effects from exposure to many frequently used pesticides
      have yet to be fully documented. Migrant Hispanic farm workers who are the
      frequent victims of such exposures are rarely studied. A neuropsychological test
      battery was administered to 21 migrant farm workers acutely exposed to Phosdrin,
      Lannate and Maneb on two occasions, and to 11 controls matched for age, sex,
      education, socioeconomic status, and ethnicity. Results revealed that two years
      after the pesticide exposures, the exposed group was significantly more impaired
      than controls on tests of psychomotor speed, dexterity, and visuospatial memory.
      Disturbing emotional symptoms were reported with significantly greater frequency
      by the exposed group in comparison to controls. Results are consistent with the
      previously reported constellation of symptoms and neuropsychological deficits
      associated with pesticide exposure.

PMID- 14589682
TI  - Primacy and recency effects in the assessment of memory using the Rey Auditory
      Verbal Learning Test.
AB  - The present study examined the manifestation of the primacy and recency effects
      in patients with anterior brain damage, posterior brain damage, and psychiatric
      inpatients with no known organic impairment. All three groups of patients
      demonstrated both a primacy and a recency effect on the Rey Auditory Verbal
      Learning Test (RAVLT). Differences among the three groups with respect to the
      magnitude of primacy and recency as well as with other variables reflecting free
      recall were nonsignificant. These findings limit the use of primacy and recency
      for the differentiation of memory deficits due to organic and nonorganic causes.

PMID- 14589683
TI  - Auditory discrimination, attention, learning, and memory in paranoid
      schizophrenics.
AB  - The present research was designed to assess auditory discrimination, attention,
      memory, and learning in paranoid schizophrenic patients using a dichotic
      listening procedure consisting of attending to a signal or a story channeled only
      to one ear. A sample of 24 paranoid schizophrenics and 24 normal controls
      volunteered. In Experiment 1, 12 schizophrenics and 12 controls attended to the
      signal while shadowing the story. The task of the other 12 clinical and 12 normal
      subjects in Experiment 2 was identical to Experiment 1 with the exception that
      the subjects did not shadow the story. In each experiment, subjects completed
      three trials as well as three evaluations of the story. The results indicated
      that schizophrenics showed substantial attentional deficits in comparison to
      normal controls.

PMID- 14589684
TI  - The place of cooperation in the examination of neuropsychological impairment.
AB  - We examined the relationship between ratings of patient cooperation and
      neuropsychological test performance in a sample (N = 333) of dementing patients
      and normal controls. We also examined the stability of the relationship in a
      subset of this same sample (N = 299) who were retested a year later. All the
      correlation coefficients in both years were significant, with a median Pearson
      of.64 in year one and.725 in year two. The test-retest reliability for ratings of
      cooperativeness over the one-year time period (rated by different examiners) was
      also significant,r =.64 (p <.0001). This analysis indicates that cooperation
      plays a significant role in neuropsychological test performance and that ratings
      of cooperativeness are relatively stable over periods of up to a year in length.

PMID- 14589685
TI  - Neuropsychological heterogeneity in schizophrenia: a consideration of abstraction
      and problem-solving abilities.
AB  - The study examines heterogeneity in abstraction and problem-solving abilities
      among schizophrenic patients through a cluster analysis of scores from the
      Halstead Category Test, the Tactual Performance Test, Part B of the Trail Making
      Test and the Wisconsin Card Sorting Test obtained from 136 male schizophrenic
      inpatients. Extensive heterogeneity was noted among the five clusters extracted,
      marked by differences in both level and pattern of performance. Efforts were made
      to find associations between cluster membership and age, education, general
      intelligence, neurological comorbidity, and medication status. Such associations
      were noted in all cases, but the role of medication was viewed as equivocal. It
      was concluded that (i) there is extensive heterogeneity in both pattern and level
      of performance of schizophrenics on tests of abstraction and problem solving; and
      (ii) Some, but not all of this heterogeneity is associated with variations in
      age, education, general intelligence, and neurological comorbidity.

PMID- 14589686
TI  - The significance of the Speech-sounds Perception Test for cerebral functions.
AB  - Results on the Speech-sounds Perception Test have been related in the literature
      to damage of the left temporal lobe in human adults, but these reports have been
      based on clinical impressions rather than controlled experimental studies. We
      compared Speech-sounds Perception Test scores and Verbal IQ for groups with left,
      right, and diffuse cerebral lesions in categories of cerebral vascular damage and
      traumatic brain injury. The only significant finding was a lower Verbal IQ in the
      group with left cerebral vascular lesions. The Speech-sounds Perception Test,
      being dependent upon attention and sustained concentration (in spite of its
      exclusively verbal content), was not found to be a reliable indicator of left
      cerebral damage. Caution should be exercised in adoption of clinical observations
      without having checked their generality by using controlled experimental
      comparisons.

PMID- 14589687
TI  - Decision strategies in neuropsychology I: determination of lateralized cerebral
      dysfunction.
AB  - This study addressed the issue concerning neuropsychological assessment and the
      determination of hemispheric lateralization. Based upon the different processing
      strategies employed by each hemisphere, several neuropsychological tests were
      hypothesized to discriminate between left hemisphere and right hemisphere damage.
      Lesion localization was determined by neurological examination,
      electroencephalography, and/or neuroradiological procedures for the 111 patients
      (47 right hemisphere, 64 left hemisphere) who were given a neuropsychological
      evaluation. Two strategies are presented for lateralizing cerebral impairment, a
      discriminant analysis and a decision process using one standard deviation as a
      cut-off point. These two strategies are compared with The Key Approach of
      Russell, Neuringer, and Goldstein (1970) and Simpson and Vega's WAIS Sign Test.
      The efficacy of decision strategies used to predict lateralization is discussed.

PMID- 14589688
TI  - Aspects of procedural memory are differentially impaired in Huntington's disease.
AB  - Procedural memory encompasses several phenomena, including motor and perceptual
      learning, cognitive rule learning and priming. These subclasses are
      differentially affected by differing neuropathologies, suggesting their
      functional independence and reliance upon different neural substrates. To test
      this hypothesis, performance on a maze learning task was compared in 15
      Huntington's disease (HD) patients and 15 normal controls (NC) to assess specific
      route learning, cognitive skill learning and the effects of route predictability
      on performance. Results revealed that the HD group: (1) showed normal learning
      curves for a specific maze route; (2) are deficient in generalizing the cognitive
      skills across mazes; and, (3) fail to improve performance on a maze with a
      predictable route relative to mazes with unpredictable routes. These results are
      interpreted as supporting the independence of procedural memory subclasses. The
      basal ganglia are suggested as important structures in mediating the ability to
      generalize skills and appreciate patterned organization in to-be-acted-upon
      stimuli.

PMID- 14589689
TI  - Short-term memory processes following closed head injury.
AB  - Survivors of severe closed head injury (CHI) were compared with neurologically
      normal matched controls on measures of short-term memory processes. The results
      indicate that patients with CHI took longer to scan their short-term memory than
      controls, and this increased disproportionately as the memory load increased. The
      number of errors made in scanning short-term memory increased for patients with
      CHI, suggesting inefficient as well as slow scanning. These differences were
      present despite equivalent memory span between groups. The results of this study
      have implications for day to day memory processes that require manipulation of
      information in short-term memory.

PMID- 14589690
TI  - Aphasic and tactile--perceptual deficits of disabled readers.
AB  - As part of a psychoeducational battery, 36 children, referred for reading and/or
      other learning difficulties, were administered the Aphasia Screening Test. the
      Tactile Finger Recognition Test, and the Finger-tip Number Writing Perception
      Test from the Halstead-Reitan Neuropsychological Test Battery for Older Children.
      The children were divided into two groups: 18 determined on the basis of a severe
      discrepancy to be eligible for learning disabilities services in the area of
      reading (RD) and 18 determined to be ineligible for such services (NRD).
      Statistical comparisons of the two groups revealed the RD group to display
      significantly more impairment on the Aphasia Screening Test and the Finger-tip
      Number Writing Perception Test.

PMID- 14589691
TI  - Intelligence and neuropsychological functioning in psychiatric disorders.
AB  - The present report examines consistency across four psychiatric conditions
      (schizophrenia, schizoaffective disorder, manic disorder, and depression) on
      neuropsychological dysfunction assessed by two different instruments, the
      Halstead-Reitan and Luri-Nebraska batteries, in relation to WAIS-IQ. Results
      indicated that the impairment scale from the Luria-Nebraska has a stable
      relationship to IQ across diagnostic groups. In contrast, the impairment index
      from the Halstead-Reitan battery shows a diagnosis-dependent relationship.
      Schizophrenics, schizoaffective and manic disorder subjects show a more uniform
      linear relationship. This is contrary to expectation given Halstead's (1947)
      distinction between "biological" and psychometric intelligence. The findings are
      discussed from the standpoint of clinical severity and outcome associated with
      contemporary diagnostic formulations of nonschizophrenic affective disorders.

PMID- 14589692
TI  - Learning impairment in male and female alcoholics.
AB  - Male VA alcoholics have been found to perform significantly poorer than
      nonalcoholics in face-name learning. Can these results be (a) replicated in a
      sample of male alcoholics from community treatment programs, (b) extended to
      female alcoholics, and (c) accounted for by childhood symptoms of attention
      deficit, conduct, and learning disorders? Seventy-six male and 66 female
      alcoholics were compared to 48 male and 49 female nonalcoholic controls on a 12
      item face-name learning test. Both male and female alcoholics had poorer learning
      scores than their respective control groups. Learning scores were unrelated to
      self reports of childhood attention deficit disorder, conduct disorder, and
      learning problems. Whether alcoholics' impaired face-name learning is due to the
      direct effect of alcohol on the brain or is a concomitant of alcoholics'
      disrupted interpersonal relationships remains to be investigated.

PMID- 14589693
TI  - Unilateral spatial neglect: biases in contralateral search and fine spatial
      attention.
AB  - Contralateral search and fine spatial attentional asymmetries, two aspects of
      hemispatial neglect, were examined in a total of 91 right brain damaged (RBD) and
      40 non-aphasic left brain damaged (LBD) stroke rehabilitation inpatients. Fine
      spatial attentional asymmetries within a hemispace were found in both RBD and LBD
      patients on the LAVA figure-match test. This finding is in contrast to Gainotti's
      hypothesis that such problems in extracting contralateral visual information are
      uniquely characteristic of RBD patients. Furthermore, the study suggests that the
      gross search and fine attentional aspects of neglect are dissociable and may
      reflect different underlying mechanisms of hemispatial neglect.

PMID- 14589694
TI  - Motor and sensory abilities with normal and academically at-risk children.
AB  - Motor and sensory abilities were assessed with children identified as normal and
      children identified as academically at-risk. The children were grouped based on
      the results of a screening procedure which consisted of tasks designed to assess
      academic readiness skills. The results indicated that the academically at-risk
      children did significantly poorer on most of the measures of motor and sensory
      functioning. Discriminant analyses indicated that the measures were generally
      more effective at classifying the normal children than the academically at-risk
      children. The results are discussed in relation to developmental models of
      neuropsychological functioning.

PMID- 14589695
TI  - Revising the Rey-Osterrieth: rating right hemisphere recall.
AB  - Recall performance of the Rey-Osterrieth Complex Figure was examined in patients
      with partial complex seizures originating from either the right or left temporal
      lobe and who underwent subsequent unilateral temporal lobectomy. A scoring system
      was developed to assess the types of errors frequently observed in the recall of
      patients with right temporal lobe epilepsy (TLE), but absent in left TLE
      patients. The scoring system was initially developed on a single group of
      patients, and then "cross-validated" on an independent sample. Performance
      analysis of the cross-validation group revealed a significant difference in the
      frequency of right hemisphere errors. In contrast, no significant difference
      using standard quantitative scoring was present. By applying the new scoring
      criteria alone, a rater blind to seizure onset correctly predicted seizure
      laterality in 15/18 of the cross-validation patients. These results suggest that
      evaluation of qualitative errors may be a valuable adjunct to standard scoring
      criteria, thereby extending the range of applications for this test.

PMID- 14589696
TI  - The effects of neuroleptics on neuropsychological test results of schizophrenics.
AB  - This paper reviews the literature investigating antipsychotic medication effects
      on the neuropsychological test results of schizophrenics. A synthesis of findings
      suggests that specific cognitive functions are differentially affected. The toxic
      effects of dopamine and muscarinic blockade adversely affect find motor
      coordination and memory respectively. A decrement in maze performance is also
      suggested, raising the possibility that frontal lobe functioning is adversely
      affected by neuroleptic treatment. There is equivocal evidence for medication
      effects on primary language skills, IQ. Halstead Reitan scores, reaction time,
      and CPT performance. Antipsychotics probably do not have large effects on
      cognitive inhibition and visual-motor coordination. The implication of these
      findings for the understanding of schizophrenia are discussed.

PMID- 14589697
TI  - Base rates of post-concussional symptoms.
AB  - Several cognitive, physical and psychological symptoms have been reported as
      common sequelae of head injury. However, these data have been reported largely in
      absence of established base rates. This study employed self-report and relative
      report questionnaires to assess base rates of these symptoms in uninjured
      subjects. Chi square analysis was used to compare the rate of symptoms reported
      by head injured subjects, relatives of head injured subjects, uninjured subjects
      and relatives of uninjured subjects. In most cases, no significant difference was
      found between the symptoms reported by the head injured group and the uninjured
      group. These results demonstrate the importance of establishing base rates of
      symptoms in non-clinical populations prior to drawing conclusions about symptoms
      in clinical populations.

PMID- 14589698
TI  - Frontal lobe damage and neuropsychological assessment.
AB  - Four cases with neuroradiologically verified frontal lobe damage are reviewed in
      terms of neuropsychological test performance and behavioral outcome. Frontal
      damage may result in a wide-spectrum of behavioral and cognitive changes that do
      not conform to a specific syndrome entity. Many of the traditional
      neuropsychological measures are insensitive to frontal lobe involvement. Various
      clinical guidelines are offered.

PMID- 14589700
TI  - The Strelau Temperament Inventory as a broad classification system.
AB  - The Strelau Temperament Inventory (STI) is an instrument designed by Jan Strelau
      to measure broad characteristics of the central nervous system. In a study
      reported here an American version of it was administered to a group of
      introductory psychology students, along with the 16PF test and an adjective check
      list. The findings of this study suggests that the STI does measure high and low
      reactivity in individuals and may have potential uses for the classification of
      temperament characteristics in individuals, particularly as a process of
      determining appropriate learning or behavioral strategies designed to enhance
      learning.

PMID- 14589701
TI  - Utility of cluster analysis in classification of mixed neuropsychiatric patients.
AB  - This study examines the hypothesis that reliable neuropsychologically-based
      subgroups can be found in a mixed neuropsychiatric patient sample (N = 600) and
      that the subtype membership will be associated with external diagnostic and case
      history variables. A modified Halstead-Reitan Neuropsychological Test Battery was
      employed. The sample was randomly divided into two groups of 300 each. Results
      show three reliable cluster analytically-based groups that differ as a function
      of level, but not pattern of performance. External validation failed to show the
      cluster groups to be significantly related to any of the neurodiagnostic or case
      history variables, except that the severely impaired group had a greater
      preponderance of organic diagnoses and a longer history of hospitalisation.
      Caution is warranted in using configural analysis of standard neuropsychological
      test batteries in an effort to identify subtypes in a mixed neuropsychiatric
      patient population.

PMID- 14589702
TI  - Options for shortening Halstead's Category Test for adults.
AB  - A serious problem with Halstead's Category Test noted by many clinicians is the
      very long time required by impaired subjects to complete it. This study proposes
      that abbreviated forms of the Category Test are clinically efficient in judging
      degree of impairment. The process of problem-solving across items of an
      abbreviated form by 64 young adult outpatients was not significantly different
      from that of 35 other young adult outpatients on the standard Category Test.
      Correlations of various short forms with the standard form were improved slightly
      when formal scoring of subtests I and II was deleted. Two clinically efficient
      short forms were identified, which correlated at .97 and .96, respectively.

PMID- 14589703
TI  - Cognitive rehabilitation after traumatic head injury.

PMID- 14589706
TI  - Editorial: software survey section.

PMID- 14589704
TI  - The clinical significance of cortical atrophy and ventricular enlargement in
      schizophrenia.
AB  - Ventricular enlargement and cortical atrophy are found in some schizophrenic
      patients. Although studies are inconclusive about the relationship between these
      brain abnormalities and schizophrenic symptoms, subtypes or genetic history,
      there may be a relationship with early brain insult or developmental abnormality.
      There is a relationship between the presence of ventricular enlargement and
      cortical atrophy with neuropsychological impairment such that the presence of
      these factors (ventriculomegaly, cortical atrophy, and neuropsychological
      impairment) in a schizophrenic individual may have a negative impact upon
      outcome. Clinical guidelines are presented.

PMID- 14589707
TI  - Patterns of intellectual performance among recently abstinent alcohol abusers on
      WAIS-R and WMS-R sub-tests.
AB  - A group of recently abstinent alcohol abusers were examined using selected
      subtests of the WAIS-R and the WMS-R. The pattern of performance on the WAIS-R
      was similar to that well established for its predecessor. A clear nonmodality
      specific memory deficit was evident on the WMS-R subtests. The theoretical and
      clinical implications of the results are briefly discussed.

PMID- 14589708
TI  - Detection of changes in material-specific memory following temporal lobectomy
      using the Wechsler Memory Scale-Revised.
AB  - To determine the utility of the Wechsler Memory Scale-Revised (WMS-R) in
      measuring material-specific memory changes, within-subject comparisons of the
      Verbal-Visual Memory Index discrepancy and discrepancy scores using short-term
      and delayed Logical Memory and Visual Reproduction subtests from the WMS-R were
      studied prior to and following temporal lobectomy among 30 patients with left
      temporal lobectomy, 30 with right temporal lobectomy, and 50 epileptic, non
      surgical controls. The groups were matched on age, sex, handedness, age at
      seizure onset, duration of epilepsy, and presurgical Verbal and Performance IQ;
      the right temporal group had a higher mean educational level (p <.05). All
      surgical patients were left hemisphere dominant for speech; those who had
      persistent postoperative seizures were excluded from study. On retesting, left
      temporal lobectomy was associated with a marked change in short-term and delayed
      memory discrepancy scores primarily due to a drop in verbal memory. Right
      temporal lobectomy was not associated with a drop in visual memory, suggesting
      that the WMS-R appears to reflect decrements in material-specific memory
      following left but not right temporal lobectomy. The nonsurgical controls showed
      increases in both short-term and delayed memory discrepancy scores due to
      increases in short-term and delayed verbal memory. Relative to these controls,
      the absence of comparable increases in verbal memory among the right temporal
      patients suggests that right temporal lobectomy may be associated with risk to
      verbal memory.

PMID- 14589709
TI  - Test-retest stability of the Satz-Mogel WAIS-R short form in a sample of normal
      persons 75 to 87 years of age.
AB  - The test-retest stability of the Sati-Mogel short form was evaluated in a sample
      of 61 persons 75 years and older. Means for age, education, and retest interval
      were 78.93 years (SD = 3.46), 9.74 years (SD = 1.91), and 64.92 days (SD =
      26.84), respectively. Test-retest coefficients were.87,.70, and.89 for the
      Verbal, Performance, and Full Scales, respectively. Subtest stability ranged
      from.28 to.83. While the stability of the Verbal and Full Scales was adequate, it
      was unacceptable for the Performance Scale. Percent agreement for gain or loss
      between the complete WAIS-R and the Satz-Mogel short form was 80.0% for the
      Verbal Scale, 55.7% for the Performance Scale, and 67.2% for the Full Scale. The
      Satz-Mogel procedure reduces the stability of the Performance Scale to an
      unacceptable level in normal elderly persons.

PMID- 14589710
TI  - Clock drawing as an assessment tool for dementia.
AB  - Clock drawing has recently been shown to lie useful in differentiating
      Alzieimer's disease patients from normal controls. Our procedure for clock
      drawing differed from other published reports in that a copy condition was
      employed and patients were asked to set clock hands to read "ten after eleven".
      We found both clock drawing procedures to be correlated with tests related to
      executive and visuospatial functioning. In both conditions, nondemented controls
      performed significantly better than demented patients. In the command condition
      there was no difference between Alzheimer patients and patients with
      cerebrovascular dementia. In the copy condition, patients with cerebrovascular
      dementia performed significantly worse than Alzheimer patients. The inclusion of
      a copy condition appears to greatly expand the utility of this test. Although our
      scoring system did not differentiate between various dementing disorders in the
      command condition, if clock drawing is used as a screening instrument, lack of
      improvement in the copy condition in comparison to the command condition may be a
      sign of a vascular involvement.

PMID- 14589712
TI  - Cross-validation of Reitan and Wolfson's Neuropsychological Deficit Scales.
AB  - Reitan and Wolfson developed and presented validity data on their
      Neuropsychological Deficit Scales and offered them as alternatives to Halstead's
      Impairment Index and Russell, Neuringer, and Goldstein's Average Impairment
      Rating. An initial cross-validation study of the scales was conducted with 73
      brain-damaged subjects and 41 pseudoneurologic controls. Brain-damaged and
      pseudoneurologic subjects differed on the General Neuropsychological Deficit
      Scale. Groups of left hemisphere, diffuse, and right hemisphere brain-damaged
      subjects differed on the Left and Right Neuropsychological Deficit Scales. The
      General Neuropsychological Deficit Scale, Impairment Index, and Average
      Impairment Rating did not differ in accuracy of subject classification. Our
      findings provide limited support for the validity of these new scales with
      patients commonly seen in clinical practice.

PMID- 14589711
TI  - A quantitative review of the diagnostic utility of the WAIS-R Fuld profile.
AB  - The prevalence of Fuld's WAIS "cholinergic deficit" profile has been examined in
      18 studies, in which the profiles of over 3700 subjects have been evaluated. When
      these data were pooled, it was found that the profile's sensitivity to dementia
      of the Alzheimer type (DAT) was only 24.1%; 77 of 319 DAT patients evaluated
      across seven studies displayed the Fuld profile. The profile's specificity was
      considerably better than its sensitivity; 93.3% (2256/2418) of normals had
      "negative" profiles, as did 88.5% (1058/1198) of non-DAT patients (e.g., patients
      with multi-infarct dementia). With its poor sensitivity, the profile's diagnostic
      utility under different base rate conditions was unimpressive. Memory indices
      possess far greater sensitivity to DAT, and have been shown to reliably
      differentiate DAT from many other causes of cognitive dysfunction. It was
      recommended that future diagnostic studies of DAT should evaluate whether
      additional neuropsychological measures, such as WAIS-R indices, enhance the
      diagnostic accuracy achieved by memory measures.

PMID- 14589713
TI  - Cross-validation of the discriminative effectiveness of the Luria-Nebraska
      Neuropsychological Battery for learning disabled adolescents.
AB  - This study was a cross-validation of the discriminative effectiveness and
      diagnostic accuracy of the Luria-Nebraska Neuropsychological Battery (LNNB).
      Subjects were a group of 31 LD adolescents and a matched group of 31 non-learning
      disabled students whose achievement fell within the low average to average range.
      Multivariate analysis of variance (MANOVA) confirmed that the LNNB was sensitive
      to group differences in analyses with either the basic or localization scales.
      Discriminant function analyses with 12 basic scales yielded overall rates of
      diagnostic accuracy ranging from 87.1% to 98.4%. A classification rule, based on
      the number of basic scale elevations, yielded 95% overall accuracy. Rates of
      overall accuracy for the eight localization scales ranged from 82.26% to 85.48%
      in discriminant function analyses. A classification rule, basedon the number of
      localization scale elevations, yielded 81% overall accuracy. The significance and
      accuracy of various indicators of dysfunction were investigated. Implications for
      the diagnosis of learning disability are discussed

PMID- 14589714
TI  - The ability of the Dementia Rating Scale to predict everyday functioning.
AB  - The Dementia Rating Scale (DRS) is a brief neuropsychological assessment battery
      designed to assess five areas of cognitive functioning in the elderly. The
      relationship between DRS performance and everyday functioning was examined for 50
      psychogeriatric patients. Everyday functioning was assessed with a standardized
      performance measure examining self-care, safety, money management, cooking,
      medication administration, and community utilization. Regression analyses were
      conducted for each of the six functional domains. In addition, correlations
      between the DRS subscales and the functional areas were computed. Results
      revealed significant predictive relationships (p <.01) between performance on the
      DRS and most functional domains. The multiple Rs ranged from .52 - .70,
      accounting for 27% to 49% of the variance. The Initiation/Perseveration subscale
      was most heavily weighted in each analysis. Significant correlations were
      obtained between subdomains of cognition and most functional areas. The findings
      provide evidence of relationships between DRS performance and functional ability.

PMID- 14589715
TI  - A note concerning misconceptions of the general public about brain injury.
AB  - A survey performed in South Louisiana disclosed that the general population held
      a number of misconceptions about the sequelae of brain injury. The authors
      cautioned that the respondents represented a convenient sample and were
      representative of only a small geographic region, and challenged others to
      conduct similar surveys in other regions of the country. The present study
      represents a replication of the Gouvier et al. survey in samples of individuals
      residing in Western New York State and Southern Ontario, Canada. The results of
      the current study are consistent with those reported by Gouvier et al., namely
      that misconceptions about brain injury are common. The impact of these
      misconceptions for individuals with brain injury are discussed.

PMID- 14589716
TI  - The role of temporal lobe and orbitofrontal cortices in olfactory memory
      function.
AB  - Differences in verbal and nonverbal olfactory identification and recognition were
      examined among three groups with brain impairment. A left cerebrovascular
      accident (LCVA) group, a right CVA (RCVA) group, and a traumatic brain injury
      (TBI) group were compared with two nonimpaired age-matched comparison groups on
      olfaction identification and recognition abilities. Odors were presented to the
      left and right nostrils, which maximized hemispheric differences in olfactory
      processing. Results showed that persons with LCVA demonstrated the greatest
      impairment on the verbal identification of odors, while persons with RCVA showed
      the most impairment on the nonverbal identification of odors. Persons with TBI
      showed an inconsistent impairment across both verbal and nonverbal odor
      identification tasks. Odor recognition was impaired in both CVA groups as well.
      In contrast, persons with TBI performed better on the delayed odor recognition
      tasks. Results are discussed in relation to hemispheric differences in processing
      olfactory information.

PMID- 14589717
TI  - Patient complaints within 1 month of mild traumatic brain injury: a controlled
      study.
AB  - Symptom complaints of 118 patients with mild traumatic brain injury (MTBI),
      within 1 month postinjury, were compared with those of 118 control participants
      without a MTBI. The MTBI and control subjects were group-matched on age, gender,
      socioeconomic status (SES), and education status. Differences in symptom
      endorsements and severity ratings were found between the groups, with 16 of the
      43 queried symptoms endorsed significantly more often (Bonferroni-corrected
      P<.00116) by MTBI patients than by controls. A total of 23 of the 43 symptoms
      were endorsed at a significantly higher severity by MTBI patients. The MTBI
      sample showed significantly higher within-group variability, with severity
      ranging from minimal to high. Perhaps because of this high variability, a
      logistic regression used to discriminate MTBI patients from controls was only
      moderately successful. This indicates that subjective complaints probably cannot
      be used, even soon after injury, to decisively distinguish individual MTBI
      patients from uninjured persons.

PMID- 14589718
TI  - Fake bad test response bias effects on the test of variables of attention.
AB  - This study investigated the effects of faking bad (FB) on the Test of Variables
      of Attention (TOVA) using subjects randomly placed into two groups. Subjects in
      Group 1 took the TOVA under normal conditions (NC) first; they were then
      requested to subtly fake bad. Group 2 subjects took the TOVA under the same fake
      bad instructions first, then took the test under normal conditions the second
      time. An analysis of the effects of test order yielded non-significant
      differences for basic TOVA variables across all four quarters, both halves and
      the total score. An analysis for group mean differences between the NC and the FB
      instructions yielded significant differences across the basic TOVA variables
      across the four quarters, two halves and total score. The FB group had excessive
      amounts of omission and commission errors, a greater response time mean (i.e.,
      slower to respond) and had greater variance around their mean response time. The
      study affirms that the professional using the TOVA needs to carefully eliminate a
      fake bad test-taking bias when subjects produce excessive test results.

PMID- 14589719
TI  - Construct validity of the PCSQ as related to the MMPI-2.
AB  - The Postconcussion Syndrome Questionnaire (PCSQ) total and factor scores were
      compared to the primary validity and clinical scales from the Minnesota
      Multiphasic Personality Inventory-II (MMPI-2) in an effort to better define the
      structure of the PCSQ. The sample used was composed of a heterogeneous group of
      79 patients referred for clinical neuropsychological evaluation. In reviewing the
      results, patients with higher PCSQ scores presented with higher clinical
      elevations on the MMPI-2. In addition, each of the PCSQ factor scores was related
      to a different pattern of MMPI-2 scales and subscales. The somatic factor was
      most associated with physical ailments, generalized distress, and social
      insecurity. In contrast, the psychological factor was related to complaints of
      dysphoria, brooding, and social connectedness. The cognitive and infrequent
      factors were related to reports of cognitive changes and unusual sensory
      experiences, respectively. The data present validation of the multifaceted nature
      of the PCSQ and its general sensitivity to subjective complaints.

PMID- 14589720
TI  - Comparative efficiency of a discrepancy analysis for the classification of
      Attention-Deficit/Hyperactivity Disorder in adults.
AB  - The present study evaluated an alternative method of neuropsychological test
      interpretation for the classification of Attention-Deficit/Hyperactivity Disorder
      (ADHD) in adults. Specifically, an intra-individual discrepancy analysis was
      implemented in which differences between intellectual functioning and performance
      on a battery of six frontal/executive tests were examined within a homogeneous
      group of ADHD adults and matched normal controls. Significant group differences
      were identified between the ADHD adults and control sample on each of the
      dependent measures, with moderate diagnostic efficiency rates for the individual
      measures and a Discrepancy Impairment Index (DII). The discrepancy analysis
      approach generated significantly greater sensitivity in detecting the presence of
      ADHD as compared to a level of performance interpretive approach. Overall, these
      results provide support for the consideration of discrepancies between
      intellectual ability and frontal/executive functioning for the assessment of
      adult ADHD.

PMID- 14589721
TI  - A confirmatory factor analysis of the WAIS-III in a clinical sample with
      crossvalidation in the standardization sample.
AB  - A maximum likelihood confirmatory factor analysis of the Wechsler Adult
      Intelligence Scale-III (WAIS-III) was performed by applying LISREL 8 to a
      clinical sample (n=328). Analyses were designed to determine which of the nine
      hypothesized oblique factor solutions could best explain intelligence as measured
      by the WAIS-III in the general clinical sample. Competing latent variable models
      were identified in previous studies and a priori model modifications were made to
      test derivations of the nine base models. Results in the clinical sample were
      crossvalidated by testing all models in the normative sample used in the
      standardization of the scale. Findings in both the clinical and standardization
      samples supported a six-factor model including Semantic Memory, Verbal Reasoning,
      Constructional Praxis, Visual Reasoning, Working Memory, and Processing Speed
      factors. Our analysis differed from that presented in the WAIS-III manual as we
      tested more complex models of intelligence in addition to the ones evaluated by
      the test publishers. As a result, a six-factor model that corresponded to an
      expanded version of a model based on Horn's Gf-Gc theory was empirically
      supported as having the best fit to the data. More complex derivations of this
      model failed to achieve sufficient goodness of fit.

PMID- 14589722
TI  - Word stem completion in young adults, elderly adults, and patients with
      Alzheimer's disease: evidence from cross-modal priming.
AB  - A cross-modality priming paradigm was used to examine the contribution of
      conceptual processing operations to performance on a word stem-completion task.
      Patients with Alzheimer's disease (AD), healthy elderly controls, and healthy
      young controls, studied words presented under two conditions, (1) visually and
      (2) orally, and were subsequently tested using a visual stem-completion task. AD
      patients were impaired relative to controls on stem completion. All groups showed
      a significant within-modality priming effect (visual study/visual test) but no
      significant cross-modal effect (auditory study/visual test), the latter taken to
      indicate a lack of a conceptual component in the stem-completion task. The
      results are discussed in relation to theories of priming deficits in AD patients.

PMID- 14589723
TI  - A reevaluation of sustained attention performance in temporal lobe epilepsy.
AB  - Reports of normal Continuous Performance Test (CPT) accuracy in patients with
      temporal lobe epilepsy (TLE) stand in contrast to a demonstration of nonspecific
      absolute reaction time (RT) deficits in this population. In this study, we
      examined CPT data from a TLE sample for potential RT deficits across three
      consecutive blocks of time during the vigil. Seventeen patients with medically
      intractable epilepsy of temporal lobe origin and 17 healthy volunteers
      participated. The Conners CPT was used to assess sustained attention over a 14
      min vigil. There were no significant group differences in accuracy. There was,
      however, a significant interaction between groups and time intervals, with
      disproportionate RT increases for patients at the end of the vigil. These
      findings are consistent with a report of nonspecific RT deficits in TLE despite
      normal accuracy scores, and further indicate impaired RT performance over time.

PMID- 14589724
TI  - Depressive symptoms and neurocognitive test scores in patients passing symptom
      validity tests.
AB  - This study examined the effect of depression on neurocognitive performance in
      patients who passed symptom validity testing. The Beck Depression Inventory (BDI)
      was used to assess depression in 420 patients with heterogeneous referral
      diagnoses (more than half of these cases were head injury or neurological
      disease). All patients had demonstrated satisfactory effort by passing two
      symptom validity tests. No differences were found on objective cognitive and
      psychomotor measures in groups sorted based on their self-reported depression. In
      contrast, on the self-report measures [i.e., Minnesota Multiphasic Personality
      Inventory-2 (MMPI-2), Symptom Checklist-90-Revised (SCL-90-R), and Memory
      Complaints Inventory (MCI)], differences were found indicating that patients with
      depression report more emotional, somatic, and cognitive problems. Contrary to
      expectation, these data suggest that depression has no impact on objective
      neurocognitive functioning.

PMID- 14589726
TI  - The continuous performance test: a window on the neural substrates for attention?
AB  - Attention is a complex process whose disturbance is considered a core deficit in
      a number of disorders [e.g., Attention Deficit Hyperactivity Disorder (ADHD),
      schizophrenia]. In 1956, Rosvold and colleagues [J. Consult. Psychol. 20 (1956)
      343.] demonstrated that the continuous performance test (CPT) as a measure of
      sustained attention was highly sensitive to brain damage or dysfunction. These
      findings have been replicated with various populations and with various versions
      of the CPT. The CPT is now cited as the most frequently used measure of attention
      in both practice and research. Across studies, results are consistent with models
      of sustained attention that involve the interaction of cortical (frontal,
      temporal, parietal), subcortical (limbic, basal ganglia), and functional systems
      including the pathways between the basal ganglia, thalamus, and frontal lobes.
      Right hemisphere involvement (asymmetric response) is also evident across
      multiple studies. As such, the CPT demonstrates sensitivity to dysfunction of the
      attentional system whether this is due to diffuse or more focal
      damage/dysfunction or in conjunction with any specific disorder. CPT performance
      can be viewed as symptom specific (attentional disturbance), but it is not
      disorder specific (e.g., ADHD). Implications for neuropsychological
      interpretation of CPT results are presented.

PMID- 14589725
TI  - Malingering on the RAVLT: Part II. Detection strategies.
AB  - In this study two potential indices of malingering derived from the Rey Auditory
      Verbal Learning Test (RAVLT) were evaluated as a means of detecting malingering.
      These were indices based on discrepancies between recognition-recall scores and
      differences in the serial position effect (SPE). Sixty undergraduate students
      were randomly assigned to one of four conditions: malingerers, malingerers-with
      warning, warning-only, and control. Incentives were offered to participants in
      all conditions to encourage faking in a believable manner (malingering
      conditions), or to encourage optimal performance (nonmalingering conditions). Two
      predictions were made. First, it was predicted that the serial position curve for
      subjects in malingering conditions would show suppression of primacy effects
      relative to nonmalingerers. Second, it was predicted that recall would be better
      than recognition for subjects in malingering conditions compared to
      nonmalingering conditions. The utility of these indices was also explored in the
      context of providing subjects' with warnings regarding use of methods to detect
      malingering. Results indicated that both indices failed to reliably differentiate
      between malingerers and nonmalingerers, and warnings failed to modify
      participants' behaviour.

PMID- 14589728
TI  - The effects of goal setting on the arithmetic performance of brain-damaged
      patients.
AB  - A goal-setting approach was used to examine the ways in which different goals
      influence the performance of 69 brain-damaged (BD) patients in an arithmetic
      task. Patients were equally assigned to two conditions: one in which a specific,
      high goal was set, and one with a "do your best" goal. Statistical analyses
      indicated that patients with a specific, high goal performed significantly better
      than patients with a "do your best" goal. No clinical or neuropsychological
      variables (e.g., time since onset of illness and memory function) were found to
      have a moderating influence on the effect of goal setting. These results indicate
      that even BD patients with cognitive and executive dysfunctions can efficiently
      self-regulate their behavior after the assignment of a high, specific goal in an
      easy laboratory task.

PMID- 14589727
TI  - Neuropsychological deficit profiles in senile dementia of the Alzheimer's type.
AB  - Recent studies using Wide Range Achievement Test-Revised (WRAT-R) Reading scores
      as estimates of premorbid abilities have demonstrated that distinct
      neuropsychological deficit profiles may be associated with specific cognitive
      disorders such as traumatic brain injury [Brain Inj. 9 (1995) 377] and lupus
      [Appl. Neuropsychol. 7 (2000) 96], and that these deficit scores predict both
      functional and financial outcomes [J. Head Trauma Rehab. 14 (1999) 220]. Although
      the main cognitive deficits associated with senile dementia of the Alzheimer's
      type (SDAT) are well known, the relative degree of impairment in each has yet to
      be adequately determined. The present study calculated indices of relative
      decline (zDiff) for 32 patients with probable SDAT by comparing estimates of
      premorbid functioning to concurrent neuropsychological test scores. The results
      suggest that intelligence is least declined in SDAT [Wechsler Adult Intelligence
      Scale-Revised (WAIS-R) FIQ, zDiff=-0.72], followed by attention [Wechsler Memory
      Scale-Revised (WMS-R) Attention Index, zDiff=-1.14], memory (WMS-R General
      Memory, zDiff=-2.12; WMS-R Delay Memory, zDiff=-2.33), speed of processing
      (Trails A, zDiff=-2.85), and cognitive flexibility (Trails B, zDiff=-5.33).
      Clinical and research implications are discussed.

PMID- 14589729
TI  - The perfidy of percentiles.
AB  - Standard texts in neuropsychology, forensic, and educational psychology recommend
      the use of percentile rank scores (PRs) in reports and in oral "feedback" on the
      grounds that percentiles are easily understood by nonpsychologists. This study
      tested that assumption, testing predictions that errors would be made consistent
      with misunderstanding PR values as units of equal intervals. Four hypotheses
      about errors in interpretation were tested using a 12-item task to assess third
      year psychology undergraduates' estimates comparing PR scores against the
      familiar metric of IQ. All predictions of significant asymmetrical and systematic
      errors of interpretation were supported. Even psychometrically educated subjects
      grossly misinterpret the meaning of PRs. Commonly recommended graphical display
      formats may unwittingly enhance these errors. Implications are most significant
      for forensic neuropsychology. Apparently low PRs representing cognitive
      performance within the Average range will typically be misinterpreted to mean
      significant impairment and, thus, may distort compensation and personal injury
      awards. Conversely, apparently high PRs representing offender recidivism risk
      within the Average range will be misinterpreted as high risk and impede release.

PMID- 14589730
TI  - Neuropsychological test performance and prediction of functional capacities among
      Spanish-speaking and English-speaking patients with dementia.
AB  - Neuropsychological measures have been widely used by clinicians to assist them in
      making judgments regarding a cognitively impaired patient's ability to
      independently perform important activities of daily living. However, important
      questions have been raised concerning the degree to which neuropsychological
      instruments can predict a broad array of specific functional capacities required
      in the home environment. In the present study, we examined 127 English-speaking
      and 56 Spanish-speaking patients with Alzheimer's disease (AD) and determined the
      extent to which various neuropsychological measures and demographic variables
      were predictive of performance on functional measures administered within the
      clinical setting. Among English-speaking AD patients, Block Design and Digit-Span
      of the WAIS-R, as well as tests of language were among the strongest predictors
      of functional performance. For Spanish-speakers, Block Design, The Mini-Mental
      State Evaluation (MMSE) and Digit Span had the optimal predictive power. When
      stepwise regression was conducted on the entire sample of 183 subjects, ethnicity
      emerged as a statistically significant predictor variable on one of the seven
      functional tests (writing a check). Despite the predictive power of several of
      the neuropsychological measures for both groups, most of the variability in
      objective functional performance could not be explained in our regression models.
      As a result, it would appear prudent to include functional measures as part of a
      comprehensive neuropsychological evaluation for dementia.

PMID- 14589731
TI  - Information processing time adds useful information to traditional recall
      measures.
AB  - Clinical work and research activity using memory tests typically use measures of
      recall. While these measures are useful, they may restrict the nature of memory
      assessments. A memory test was developed to record encoding and recall times.
      Analyses were then conducted to determine whether these encoding and recall times
      related to recall performance. Results indicated that encoding time and recall
      time related significantly to recall performance. Data also revealed that while
      the strength of the relationship between encoding time and recall errors
      generally remained constant, the relationship between recall time and recall
      errors decreased as task demands increased.

PMID- 14589732
TI  - Single versus composite score discriminative validity with the Halstead-Reitan
      Battery and the Stroop Test in mild brain injury.
AB  - The predictive validity of single measures from the Halstead-Reitan
      Neuropsychological Test Battery and Stroop Neuropsychological Screening Test were
      evaluated in a sample of 25 mild traumatic brain-injured and 25 neurologically
      normal subjects and compared to the accuracy of composite score measures,
      specifically the General Neuropsychological Deficit Scale and the Halstead
      Impairment Index. Whereas several measures from the Halstead Impairment Index
      achieved significantly better than chance prediction, the two summary measures
      from the Halstead-Reitan Neuropsychological Test Battery predicted the
      neurological status of the subjects with the most accuracy. The Stroop
      Neuropsychological Screening Test did not perform well as a single predictor.
      Together, these results suggest that single-measure screening tests do not
      predict mild brain-injury as well as composite neuropsychological measures. The
      results also give credence to the argument of comprehensive testing for brain
      injured patients whose injuries are deemed medically mild.

PMID- 14589733
TI  - Changes in immediate visual memory predict cognitive impairment.
AB  - Six-year changes in immediate visual memory performance assessed by the Benton
      Visual Retention (BVR) test predicted Alzheimer's disease (AD) prior to its
      onset. Subjects of this study were 371 community-dwelling adult participants in
      the Baltimore Longitudinal Study of Aging, seven of whom received probable or
      definite AD diagnoses using DSM-III-R and NINCDS-ADRDA criteria. Subjects with
      diagnoses of AD had larger changes in immediate memory performance over the 6
      year interval prior to the estimated onset of their disease than subjects without
      AD. Six-year longitudinal change as well as level in immediate visual memory
      performance also predicted subsequent cognitive performance 6-15 and 16-22 years
      later, even after adjusting for the influences of age, general ability, and
      initial immediate memory. These results provide evidence that change and level in
      immediate visual memory performance has long-term prognostic significance over as
      many as 16-22 years. These results further suggest that change in recent memory
      performance, an important component in AD diagnoses, may be an important
      precursor of the development of the disease.

PMID- 14589734
TI  - Cross-validation of the General Neuropsychological Deficit Scale (GNDS).
AB  - Sherer and Adams (1993) reported "limited support" for the validity of Reitan and
      Wolfson's (1988) Neuropsychological Deficit Scales. The present study was
      designed to cross-validate one of these scales--the General Neuropsychological
      Deficit Scale (GNDS). The results were in relatively close agreement with the
      findings originally reported by Reitan and Wolfson, and indicate that the
      findings of Sherer and Adams also generally support the validity of the GNDS.

PMID- 14589735
TI  - Alternate forms of the Auditory-Verbal Learning Test: issues of test
      comparability, longitudinal reliability, and moderating demographic variables.
AB  - The present investigation examines the alternate-form and longitudinal
      reliability of two versions of the Auditory-Verbal Learning Test (AVLT) on a
      large, multiregional, healthy male sample. Subjects included 2,059 bisexual and
      homosexual HIV-seronegative males recruited from the Multicenter AIDS Cohort
      Study from centers in Baltimore, Chicago, Los Angeles, and Pittsburgh. The
      findings revealed no significant differences between forms upon initial or 1-year
      longitudinal administration, supporting the equivalence of the two versions.
      However, significant practice effects were noted longitudinally, arguing for the
      need of appropriate retest normative data. Furthermore, as age, ethnicity, and
      education were found to significantly affect test performance, it is recommended
      that normative data be interpreted according to these variables. In addition to
      providing normative and longitudinal data, this investigation presents
      information concerning the use and limitations of the alternate forms of the
      AVLT.

PMID- 14589736
TI  - Reading on the Wide Range Achievement Test-Revised and parental education as
      predictors of IQ: comparison with the Barona formula.
AB  - It is frequently necessary in research and clinical evaluations to obtain
      estimates of premorbid intelligence (IQ) which are separate from measured IQ.
      There is evidence that word reading may be useful in this aim. In order to
      determine the potential of the Wide Range Achievement Test-Revised (WRAT-R)
      reading subtest (READ) as an estimate of premorbid IQ, the present study examined
      the relationship between READ and IQ in healthy subjects. Consistent with other
      findings, READ accounted for a significant amount of variance in Verbal,
      Performance, and Full Scale IQ. Race and parental education, the latter being a
      variable not previously examined in this literature, accounted for incrementally
      valid variance in IQ beyond READ. The predictive power of these variables
      compares favorably with estimates made by the Barona IQ estimation formula, which
      uses only demographic information.

PMID- 14589737
TI  - Neuropsychological outcome and quantitative neuroimaging in mild head injury.
AB  - Four cases of well-documented mild traumatic brain injury (Glasgow Coma scores >
      or = 13) in whom preinjury neuroimaging studies were available (three with
      computerized tomography and one with magnetic resonance [MR] imaging) were
      examined in terms of postinjury MR imaging and neuropsychological outcome. All
      scans were subjected to quantitative analysis by measuring ventricular volumes
      and calculating a ventricle-to-brain ratio. Since ventricular measurements
      provide an index of parenchymal integrity, any systematic increase in postinjury
      ventricle size would be an indication of tissue loss. In addition to using the
      preinjury scan for a within-subject design in comparing postinjury changes,
      similar MR measures were obtained on a group of medical controls. Despite
      neuropsychological findings that suggested significant sequelae, quantitative
      postinjury MR studies did not show differences between preinjury neuroimaging or
      medical control subjects.

PMID- 14589740
TI  - Contributing factors to depressed mood in Multiple Sclerosis.
AB  - By applying the behavioral theory of Lewinsohn et al. [1985. An integrative
      theory of depression. In: S. Reiss, & R. R. Bootzin (Eds.), Theoretical issues in
      behavior therapy (pp. 331-359). San Diego, CA: Academic Press.] to multiple
      sclerosis (MS), it was hypothesized that physical disability, fatigue, and
      psychosocial dysfunction would be significantly predictive of depressed mood in
      MS patients. Seventy-six MS patients completed the following measures: the
      Sickness Impact Profile (SIP), the Fatigue Impact Scale (FIS), and the mood
      subscale from the Chicago Multiscale Depression Inventory (CMDI). Structural
      equation modeling revealed that physical disability and fatigue were indirectly
      predictive of depressed mood via their effects on recreational functioning.
      Fatigue also had a direct effect on mood. If reductions in recreational
      activities actually cause decrements in mood, depressed mood in MS may be
      treatable by helping patients identify recreational activities that they can
      enjoy regardless of physical or fatigue-related difficulties.

PMID- 14589741
TI  - Using the Tactile Form Recognition Test to differentiate persons with brain
      damage from control subjects.
AB  - The Tactile Form Recognition (TFR) Test, which evaluates stereognosis in each
      hand and requires less than 15 min for administration, was given individually to
      50 persons with brain damage and 50 controls who were essentially equivalent in
      age and education. Scores for the two groups yielded mean values that were
      different at a statistically significant level. Evaluation of the two
      distributions of scores yielded a cutoff score that had an accuracy rate of 82%
      for the controls and 84% for the persons with brain damage. The results suggest
      that the TFR Test is a valid and useful procedure for differentiating persons
      with brain damage from controls and, thus, can serve effectively, in conjunction
      with tests of higher-level brain functions, in neuropsychological evaluation of
      individual persons.

PMID- 14589742
TI  - Elderly norms for the Spot-the-Word test.
AB  - This study provides population-based normative data for healthy, community
      dwelling American elderly on the Spot-the-Word test (STW). The effects of age,
      education, and gender on STW performance are also investigated. Given previously
      limited normative data for the elderly, the current norms expand the clinical
      utility of STW as an estimate of premorbid intelligence. Significant but small
      effects were found for age on STW performance. Significant and moderate effects
      were found for education. Therefore, normative adjustments are provided for
      education. Consistent with previous research, no effect was found for gender.

PMID- 14589743
TI  - Regression-predicted age norms for the Children's Orientation and Amnesia Test.
AB  - The Children's Orientation and Amnesia Test (COAT) was developed to assess
      posttraumatic amnesia (PTA) and cognitive functioning in children and adolescents
      who are in the early stages of recovery from traumatic brain injury. The COAT is
      composed of 16 items designed to assess general orientation, temporal
      orientation, and memory. The original norms are inadequate for several age groups
      because they were based on small sample sizes and may have been compromised by
      ceiling effects. In this study, normative data were collected for children
      between the ages of 8 and 13 (N=248). Regression-predicted age norms were
      calculated and presented in tabular form. These results provide important
      reference data for interpreting COAT scores of children who have sustained
      traumatic brain injuries.

PMID- 14589744
TI  - A multidimensional approach towards malingering detection.
AB  - A validation study using 62 subjects was conducted on the Multidimensional
      Investigation of Neuropsychological Dissimulation (MIND), a new
      neuropsychological instrument used to detect exaggeration of brain-injury
      symptoms. This instrument has eight scoring indices that use multiple,
      empirically based strategies to detect poor effort. Discriminant function
      analysis was used to classify three groups of subjects: normals responding in a
      sincere manner (N=24); normals who were educated about mild to moderate head
      injuries and given substantial incentives to malinger without obvious detection
      (N=21); and clinically diagnosed, brain-injured patients with mild to moderate
      impairments (N=17). A univariate F test indicated significant group differences
      on six of the eight original predictor variables. Using these six variables,
      there was an overall classification rate of 68%, reflecting only a 10% false
      negative rate in the dissimulating group. For a two-group classification (i.e.,
      dissimulating and mildly to moderately brain-injured subjects), an 82% overall
      accuracy rate was achieved. The MIND appears to have potential for identifying
      individuals exaggerating mild to moderate neuropsychological deficits.

PMID- 14589745
TI  - A validity index for the MMPI-2.
AB  - There have been numerous methods developed for the detection of valid profiles on
      the Minnesota Multiphasic Personality Inventory (MMPI)-2. The current study
      examined a method of combining seven different validity scales of the MMPI-2 into
      a common weighted method in assessing malingering in chronic pain patients. The
      weighted method was able to correctly classify 100% of nonlitigants, using a
      cutoff score of > or =5. The findings of this study suggest that chronic pain
      patients in litigation produce a different profile on the MMPI-2 validity scales
      than do nonlitigants. In a group of knowledgeable actors (malingerers), 86% was
      correctly classified. The overall finding showed 100% specificity and 86%
      sensitivity. The findings support the need for multiple validity scales to be
      examined in determining a valid profile. The weighted validity scales method was
      robust enough to account for "emotional distress" and still identify invalid MMPI
      2 performance.

PMID- 14589746
TI  - 3MS normative data for the elderly.
AB  - The Modified Mini-Mental State Examination (3MS) was developed to overcome
      shortcomings of the Mini-Mental Status Exam (MMSE), specifically its narrow range
      of possible scores and ceiling effects. Several studies have examined the
      psychometric characteristics of the 3MS, showing an improvement in reliability
      and increased sensitivity in detecting dementia in comparison to the MMSE.
      Despite research supporting the favorable psychometric features of the 3MS, the
      clinical value of the instrument is restricted by limited normative data,
      especially for the elderly population. In this study, we examine the influence of
      demographic characteristics on 3MS scores and present descriptive data for a
      sample of 393 community-dwelling older adults. Normative data, based on age and
      with adjustments for education, are provided for clinical use.

PMID- 14589747
TI  - Beyond memory impairment: cognitive changes in Alzheimer's disease.
AB  - In addition to memory impairment, deficits in other cognitive processes are
      common in the advanced stages of Alzheimer's disease (AD). The diagnosis of AD
      does not consider the relative prevalence of deficits in cognitive areas other
      than memory. We report on the prevalence of aphasia, apraxia, and other cognitive
      changes in individuals from a large representative sample of elderly Canadians.
      The proportion of these symptoms and the relevant neuropsychological test
      performance were compared in a group of 749 people over 65 years in age with AD
      and a control group of 563 people without cognitive impairment. Agnosia was less
      common in both groups than were deficits in complex visuomotor tasks, abstract
      thinking, aphasia, and constructional defects. The occurrence of all symptoms
      increased, and levels of performance on relevant neuropsychological tests
      decreased, with severity of Alzheimer disease. The tests did not, however,
      distinguish between possible and probable AD. Both these diagnostic groups showed
      similar levels of performance, which suggests that this distinction is not
      clinically meaningful.

PMID- 14589748
TI  - Corpus callosum atrophy and neuropsychological outcome following carbon monoxide
      poisoning.
AB  - This study assessed the effects of carbon monoxide (CO) poisoning on the corpus
      callosum (CC). Sixty-two CO-poisoned patients had MRI scans and a battery of
      neuropsychological tests within 24 h (day of exposure) of CO poisoning and at 6
      months post CO exposure. Serial quantitative magnetic resonance imaging (QMRI)
      analysis of the CC was carried out, with the day of exposure scans compared to
      the 6-month scans. There was no difference between normal subjects' CC and the
      baseline scans in the CO-poisoned patients. We detected a 15-mm2 loss in the
      cross-sectional surface area of the CC between baseline and the 6-month follow-up
      scans. The effect on the CC was generalized atrophy rather than CC subregion
      specific changes. Neuropsychological test results performed at baseline and at 6
      months did not correlate with the level of CC atrophy. Independent of any CC
      effects, the patients exhibited impaired memory, attention, and executive
      functioning on baseline testing, with variable improvement in cognitive function
      at 6 months. Quantitative MRI analysis allows for the detection of subtle CC
      changes that may not otherwise be observed following CO poisoning. The long-term
      effects of CO on the brain have been historically underestimated; however, we
      found subtle but significant CC atrophy and cognitive impairments following CO
      poisoning.

PMID- 14589749
TI  - Cross-validation of indicators of malingering: a comparison of nine
      neuropsychological tests, four tests of malingering, and behavioral observations.
AB  - Few studies to date have cross-validated indicators of malingering that have been
      suggested on various neuropsychological tests. This study presents data cross
      validating several indicators of malingering on neuropsychological tests, as well
      as on tests of malingering and via behavioral observations. It incorporates
      methodological recommendations by Rogers [Researching dissimulation. In: R.
      Rogers (Ed.), Clinical assessment of malingering and deception (pp. 309-327). New
      York: Guilford Press.] resulting in an ecologically valid design utilizing
      college students with a history of mild head injury as analog malingerers.
      Results indicated that the Letter Memory Test (LMT) and the Digit Memory Test
      (DMT) attained the highest hit rates for the detection of malingering, while the
      sensitivity of many other measures declined on cross-validation.

PMID- 14589750
TI  - Assessing nonverbal memory with the Biber Figure Learning Test-Extended in
      temporal lobe epilepsy patients.
AB  - Material-specific memory dysfunction was assessed using a nonverbal,
      visuospatial, supraspan learning test, the Biber Figure Learning Test-Extended
      (BFLT-E), in 71 left-hemisphere language-dominant epilepsy patients prior to
      anterior temporal lobectomy (ATL) and in 48 age-matched healthy subjects. Two
      matched forms of the BFLT-E yielded comparable scores, indicating that this task
      may be used to track memory performance over time in individual patients. Right
      temporal lobe epilepsy (RTLE) and left temporal lobe epilepsy (LTLE) patients
      performed below healthy subjects on all free-recall measures. RTLE, but not LTLE,
      patients also differed from healthy subjects in recognition memory
      discrimination. Furthermore, the RTLE patients performed below LTLE patients on
      measures specific to long-term memory abilities. The BFLT-E appears to be a
      useful clinical tool for assessing different components of visuospatial memory in
      patients with lateralized mesial temporal lobe (MTL) dysfunction. The test is
      sensitive to visuoconstructional problems associated with various types of brain
      damage, but it also distinguishes material-specific, nonverbal, visuospatial
      memory impairments in patients with neurological dysfunction in the non language
      dominant right temporal lobe.

PMID- 14589751
TI  - A more robust predictor of ideomotor dyspraxia: study on an alternative scoring
      method of the Berges-Lezine's Imitation of Gestures test.
AB  - Use of the traditional Berges-Lezine standardization [Test d'imitation de gestes
      (1963).] allowed us to confirm praxic disorders in children who are encountering
      obvious motor difficulties. However, in comparison to other neuropsychological
      assessments carried out on these children, it does not enable us to precociously
      pinpoint disorders in praxic organization. By means of a newly evaluated method
      (1997) developed on the basis of the Berges-Lezine Imitation of Gestures test
      (1963), we retroactively assessed a group of children (N=10) who had been
      observed in a longitudinal study at the age of 3-5 years and at 7-8 years and
      assessed with the Berges-Lezine version (1963) of the Imitation of Gestures test.
      Our revised test (1997) takes into account the quantitative factor of success, as
      well as the qualitative factor of movement planning. It facilitates the early
      detection of motor organization disorders, in correlation with other
      neuropsychological assessments carried out on these children. Comparative
      clinical findings with the same group of children tested using the Berges-Lezine
      version and ours indicate that our version detects, more robustly, children
      encountering difficulties resulting from ideomotor dyspraxia, not identified by
      the Berges-Lezine test (1963). Our alternative scoring method of Berges-Lezine's
      test contributes largely to early detection of instrumental difficulties in
      children. Additionally, its predictive capacity makes it possible to apprehend
      disorders in distal and digital neuromotor functions.

PMID- 14589752
TI  - Verbal IQ-performance IQ differentials in traumatic brain injury samples.
AB  - Several studies of head trauma utilizing the Wechsler Adult Intelligence Scale
      (WAIS) reported large sample differentials between verbal IQ (VIQ) and
      performance IQ (PIQ), leading some writers to claim that the VIQ is largely
      unaffected by traumatic brain injury (TBI), and that a superiority of VIQ over
      PIQ should be expected. In contrast, our review of Wechsler Adult Intelligence
      Scale-Revised (WAIS-R) studies indicates that although TBI sample PIQ means are
      often depressed relative to VIQ means, the differences are small and sometimes in
      the opposite direction. Possible reasons for the discrepancy between our WAIS-R
      review and those of an earlier review of WAIS studies are discussed. Clinically,
      the lack of a VIQ-PIQ difference should never be used to infer that a TBI has not
      occurred.

PMID- 14589753
TI  - The effects of depression and anxiety on memory performance.
AB  - The effects of depression and anxiety, as assessed by MMPI D and Pt scales, on
      memory performance was examined in 3999 veterans who completed the California
      Verbal Learning Test (CVLT). Depressive symptoms (without anxiety) had an adverse
      effect on immediate recall of new information and the total amount (but not rate)
      of acquisition; however, retrieval and retention were unaffected. On the other
      hand, high levels of anxiety did not have significant detrimental effects on any
      aspect of memory functioning assessed including immediate recall, total amount
      acquired, retention, and retrieval of novel information. However, when depression
      was compounded by anxiety, there was not only an adverse effect on immediate
      recall and amount (but not rate) of acquisition, but also on the retrieval of
      newly learned information. We conclude that the presence of comorbid anxiety may,
      in part, account for the variability in previous research findings regarding the
      effects of depression on memory functioning.

PMID- 14589754
TI  - Malingering, coaching, and the serial position effect.
AB  - The normal pattern of performance on list-learning tasks is to recall more words
      from the beginning (primacy) and end (recency) of the list. This pattern is also
      seen in patients with closed head injury, but malingerers tend to recall less
      words from the beginning of word lists, leading to a suppressed primacy effect.
      The present study examined this pattern on both learning trials and delayed
      recall of the Auditory Verbal Learning Test (AVLT) in 34 persons performing with
      normal effort, 38 naive malingerers, 33 warned malingerers, and 29 head-injured
      patients. Both malingering groups had lower scores on the primacy portion of the
      list during learning trials, while normals and head-injured patients had normal
      serial position curves. During delayed recall, normals and head-injured patients
      did better than the two malingering groups on middle and recency portions of the
      list. Findings suggest that the serial position effect during learning trials may
      be a useful pattern of performance to watch for when suspicious of malingering.

PMID- 14589755
TI  - Dichotic listening: expanded norms and clinical application.
AB  - The object of this study was to provide an expanded normative base for the
      Dichotic Word Listening Test (DWLT), with particular emphasis on the performance
      of older individuals. The normative study consisted of 336 community living
      volunteers. These new norms were used to compare several groups of neurologically
      impaired patient groups. DWLT was found to be sensitive to the presence of brain
      injury, and also to the degree of acute injury as measured by loss of
      consciousness. The results of the short form version of the DWLT test showed 100%
      specificity and 60% sensitivity for mildly brain-injured patients to 80%
      sensitivity for more severely brain-injured patients. The respective
      sensitivities for Left CVA and Right CVA were 55% and 88%. The present findings
      suggest that the DWLT is a valid and easy to use clinical tool.

PMID- 14589758
TI  - National Academy of Neuropsychology Abstracts from the 21st Annual Meeting, San
      Francisco, California, October 31-November 3, 2001.

PMID- 14589756
TI  - Enduring effects of concussion in youth athletes.
AB  - The purpose of this study was to explore the mild, enduring effects of concussion
      in otherwise healthy youth athletes. Reported history of concussion and cognitive
      functioning was examined in an initial sample of 35 youth athletes, 21 of whom
      were considered healthy volunteers (No Recent Concussion within the past 6
      months) with no identified medical or neuropsychological difficulties related to
      concussion. The remaining 14 volunteers had each sustained a concussion within 1
      week of testing (Recent Concussion). Significant differences in performances on a
      general cognitive measure, and specifically in the area of attention, were found
      as a function of number of concussions reported by the No Recent Concussion
      athletes. Furthermore, on some of the measures, No Recent Concussion athletes
      with a history of two or more concussions appeared to resemble Recent Concussion
      athletes more so than No Recent Concussion athletes with a history of one or no
      concussion. The importance of assessment of youth concussion and the use of the
      Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) for
      this purpose are discussed.

PMID- 14589782
TI  - Malingering on the RAVLT. Part I. Deterrence strategies.
AB  - The effect of warning regarding detection of malingering on the Rey Auditory
      Verbal Learning Test (RAVLT) was examined in this study. Sixty undergraduate
      students were randomly assigned to one of four conditions: malingerers,
      malingerers-with-warnings, warning-only, and control. An incentive that appeared
      differential, but was an actual constant reward, was offered to participants who
      could fake in a believable manner (for those in malingering conditions), or to
      those who performed to the best of their ability (non-malingering conditions). It
      was predicted that warning participants about the possibility that faking could
      be detected would modify the behaviour of malingerers, but not those instructed
      to perform to the best of their ability. Warning had no effect on behaviour in
      either condition, which was consistent with expectations for the warning-only
      group, but not for the malingering group. Results are discussed in terms of the
      ethical and legal issues associated with malingering in neuropsychological
      practice.

PMID- 14589783
TI  - Neuropsychological dysfunction in patients suffering from end-stage chronic
      obstructive pulmonary disease.
AB  - Few studies have examined the neuropsychological sequelae associated with end
      stage pulmonary disease. Neuropsychological data are presented for 47 patients
      with end-stage chronic obstructive pulmonary disease (COPD) who were being
      evaluated as potential candidates for lung transplantation. Although patients
      exhibited a diversity of neurocognitive deficits, their highest frequencies of
      impairment were found on the Selective Reminding Test (SRT). Specifically, over
      50% of the patients completing the SRT exhibited impaired immediate free recall
      and consistent long-term retrieval deficits, while more than 44% of these
      individuals displayed deficient long-term retrieval. Deficient SRT long-term
      storage strategies, cued recall, and delayed recall were exhibited by between 26%
      and 35% of these patients, while more than 32% of this sample displayed elevated
      numbers of intrusion errors. Over 31% of the patients completing the Wisconsin
      Card Sorting Test (WCST) failed to achieve the expected number of categories on
      this measure, while more than 23% of these individuals demonstrated elevated
      numbers of perseverative errors and total errors. Clinically notable frequencies
      of impairment (greater than 20% of the sample) were also found on the Trail
      Making Test (TMT): Part B and the Wechsler Memory Scale-R (WMS-R) Visual
      Reproduction II subtest. Minnesota Multiphasic Personality Inventory-2 (MMPI-2)
      personality assessments indicated that patients were experiencing a diversity of
      somatic complaints and that they may have been functioning at a reduced level of
      efficiency. These findings are discussed in light of patients' end-stage COPD and
      factors possibly contributing to their neuropsychological test performances.
      Implications for clinical practice and future research are also included.

PMID- 14589784
TI  - Statistics to tell the truth, the whole truth, and nothing but the truth:
      formulae, illustrative numerical examples, and heuristic interpretation of effect
      size analyses for neuropsychological researchers.
AB  - If, as neuropsychologists, we think of the relationship between brain and
      behavior as the same as that between truth and reality, we must be equipped with
      statistical procedures that are coherent in terms of what we measure and what it
      represents. I believe that this necessary statistical procedure is effect size
      analysis, and without it, I believe that we fail to tell the truth, the whole
      truth, and nothing but the truth when describing our neuropsychological research.
      Accordingly, I review here the standard calculations of commonly employed effect
      sizes in two group designs and show how to adjust some familiar (and perhaps not
      so familiar) formulae using illustrative numerical examples. I also put forth an
      argument to adopt Cohen's measure as an expression of effect size based on its
      apropos to neuropsychological research. It is also argued that the interpretation
      of the magnitude of an effect size should depend on context, and not on pre
      established heuristic benchmarks. It is noted, however, that effect sizes greater
      than 3.0 (OL%<5) might seem particularly appropriate when evaluating the
      sensitivity of neuropsychological tasks and in establishing test markers in
      neuropsychological disorders.

PMID- 14589785
TI  - The Word Completion Memory Test (WCMT): a new test to detect malingered memory
      deficits.
AB  - In recent years, much research has focused on developing tests to detect
      malingering. A drawback of existing tests is their poor ability to detect
      malingerers possessing more "sophisticated" knowledge of neuropsychological
      deficits. The current study presents preliminary validation data on a new
      measure, the Word Completion Memory Test (WCMT), which is the first malingering
      test to utilize a sophisticated coaching methodology in its development. The WCMT
      was administered to control participants, memory-impaired patients, and coached
      simulators. The coached simulators were provided with specific information about
      and examples of memory deficits commonly experienced following closed head injury
      (CHI; e.g., anterograde vs. retrograde amnesia). They also read a detailed
      scenario describing the lifestyle and motivations likely experienced by CHI
      litigants, and then practiced their roles by taking a quiz about their deficits.
      Results showed that 93% of coached simulators and 100% of control and memory
      impaired participants were correctly classified by the WCMT.

PMID- 14589786
TI  - Premorbid IQ estimates from a multiple aptitude test battery: regression vs.
      equating.
AB  - Estimation of premorbid abilities remains an integral part of neuropsychological
      evaluations. Several methods of indirect estimation have been suggested in the
      literature. Many of these methods are based in prediction via linear regression.
      Unfortunately, linear regression has the well-reported tendency to underpredict
      high IQ scores and overpredict low IQ scores. This can be shown to be an
      unavoidable statistical artifact of linear regression. We demonstrate a procedure
      to estimate premorbid IQ without the regression artifact. The procedure has two
      steps: confirmation of construct equivalence and psychometric equating. An
      example using real data is presented which shows the regression to the mean
      problem with prediction and compares it to the results from equating.

PMID- 14589787
TI  - A comparison of complaints by mild brain injury claimants and other claimants
      describing subjective experiences immediately following their injury.
AB  - This study compares the rate of postconcussive (PCS) symptoms at the time of
      injury for mild traumatic brain injury (MTBI; N=24) claimants and claimants
      reporting other forms of injury (OI; N=66). On checklists surveying their
      complaints immediately after their injury, MTBI and OI claimants reported similar
      levels of many PCS complaints, e.g., dazed, confused, dizzy, disoriented, trouble
      concentrating, numbness or loss of sensation, and loss of memory for some of what
      happened. One in four of the OI samples reported partial loss of consciousness
      (LOC), and one-third reported loss of memory for some of what happened. About 67%
      of the MTBI sample reported being confused and 71% dazed, but so did many of the
      OI sample (52% dazed, 65% confused). The authors suggest that classical PCS
      complaints experienced immediately after an injury are so nonspecific that they
      have little diagnostic specificity.

PMID- 14590151
TI  - Alcohol dementia: "cortical" or "subcortical" dementia?
AB  - Most dementias are considered to exhibit either a predominantly "cortical" (e.g.
      Alzheimer's disease, AD) or "subcortical" (e.g. Parkinson's disease) pattern. A
      double dissociation has been reported, such that cortical and subcortical
      dementias can be differentiated based on performance on tests of declarative and
      procedural learning. The goal of this study was to determine if subjects with
      alcohol dementia exhibit a predominantly cortical or subcortical dementia
      profile. The performance of 10 elderly subjects diagnosed with alcohol dementia,
      29 elderly subjects with histories of alcohol dependence but who were not
      demented, and 11 subjects with AD was compared to 20 elderly control subjects.
      The results indicated that the procedural learning task did not differentiate
      among the groups, whereas the discriminability index from the California Learning
      Test (the declarative learning task) did. Thus, alcohol dementia cannot clearly
      be ascribed to either dementia classification.

PMID- 14590152
TI  - Internal consistency, temporal stability, and reproducibility of individual index
      scores of the Test of Variables of Attention in children with attention
      deficit/hyperactivity disorder.
AB  - Psychometric properties of the Test of Variables of Attention (TOVA) were
      examined in a cohort of children (n=63) strictly diagnosed with attention
      deficit/hyperactivity disorder (AD/HD). Internal consistency was assessed via
      correlational analyses to determine the degree of agreement among various test
      portions. The temporal stability of errors of omission, errors of commission,
      response time, and response time variability was evaluated using test-retest
      reliability. Reproducibility of individual scores for the same indices was
      assessed using the Bland-Altman procedure. Select TOVA index scores exhibited
      high internal consistency in this cohort. Although the temporal stability of
      group scores (test-retest reliability) was satisfactory, individual test scores
      were less reproducible. Temporal stability and individual test-retest score
      agreement were greater for response time and response time variability than for
      errors of omission and errors of commission.

PMID- 14590153
TI  - Different underlying mechanisms for deficits in concept formation in dementia.
AB  - We investigated the different mechanisms that may underlie deficits in verbal
      concept formation among patients with Alzheimer's disease (AD) and ischaemic
      vascular dementia (IVD) associated with periventricular and deep white matter
      alterations. Concept formation was assessed with the WAIS-R Similarities subtest
      (SIM). Two types of errors were re-coded from the 0-point responses as scored by
      the WAIS-R manual. In set errors (e.g., dog-lion "they're alive") were coded when
      patients reported a very vague superordinate concept for the word pair. Out of
      set responses (e.g., dog-lion "the lion roars and the dog barks") were coded when
      a response was clearly out of mental set, i.e., when participants were unable to
      provide a superordinate concept for the word pair. Between-group comparisons
      demonstrated no difference in SIM test performance according to the scoring
      system described in the WAIS-R manual. Nonetheless, AD patients produced a
      greater proportion of in set errors, while IVD patients produced a greater
      proportion of out of set errors. Out of set errors were highly associated with
      measures of executive function, while in set errors were associated with measures
      related to delayed recognition memory and semantic intrusion errors. We conclude
      that the underlying deficits that contribute to poor concept formation differ
      between AD and IVD patients. In IVD impaired concept formation is related to
      deficits in the executive systems necessary to monitor responses and sustain
      mental set. In AD, by contrast, the deficit appears to be secondary to impaired
      verbal response selection.

PMID- 14590154
TI  - Persistent neurobehavioral problems following mild traumatic brain injury.
AB  - Accumulating research documents typical rates in the range of 85% of mild
      traumatic brain injury (MTBI) showing prompt, complete resolution with 15%
      suffering from persistent neurobehavioral impairments. Studies of neurobehavioral
      symptoms of MTBI have not separated these two populations, resulting in either
      inconclusive or contradictory conclusions concerning the relationship of MTBI
      with residual behavioral problems. This project studied 70 MTBI patients with
      persistent neurobehavioral problems at two time intervals post-injury to
      determine whether there are consistent neurobehavioral patterns considered to be
      sequelae of MTBI. A matched group of 40 normal subjects provided control data.
      While most behavioral problems showed improvement, 21% tended to show significant
      behavioral impairment compared to controls at 12 or more months post-injury.
      Neurochemical bases of neuronal degeneration may account for some of the
      behavioral deterioration following MTBI.

PMID- 14590155
TI  - The role of the frontal lobes in memory: evidence from unilateral frontal
      resections for relief of intractable epilepsy.
AB  - The current investigation explored processes associated with memory deficits in
      patients with frontal lobe dysfunction. Specifically, we examined deficits
      associated with the encoding, consolidation, and retrieval of information in
      memory in 53 patients who underwent either a unilateral frontal (N=13) or
      temporal (N=40) lobe resection for relief of intractable epilepsy. Post-surgical
      memory scores indicated that the frontal group and the temporal group did not
      differ in consolidation of information, as defined by the information forgotten
      between immediate and delayed recall. Instead, the temporal group evidenced
      significantly poorer recall of verbal information at both immediate and delayed
      recall. This effect was especially strong in the left temporal group for the
      recall of verbal information. Although no group differences were observed in the
      degree to which patients semantically organized information or made recency
      discriminations, the frontal group exhibited significantly weaker release from
      proactive interference than the temporal group, suggesting some impairment in
      encoding and retrieval processes associated with frontal lobe dysfunction.

PMID- 14590156
TI  - Neuropsychological performance deficits in adults with attention
      deficit/hyperactivity disorder.
AB  - Neuropsychological deficits in children diagnosed with attention
      deficit/hyperactivity disorder (ADHD) have been well documented utilizing various
      neuropsychological tests. Only recently has research begun to examine if similar
      deficits are present in adults with ADHD. A neuropsychological testing battery
      was constructed that assessed verbal learning and memory, psychomotor speed, and
      sustained attention--all demonstrated to be deficient in individuals with ADHD.
      Fifty-six self-referred nonmedicated adults with a DSM-IV diagnosis of ADHD and
      38 normal comparison adults participated. ADHD adults demonstrated verbal and
      nonverbal memory deficits and decreased psychomotor speed compared to normal
      controls. Differences between ADHD and normal adults were not documented on
      traditional measures of executive functioning. A pattern of results emerged
      whereby ADHD adults' performance, particularly with regard to psychomotor speed,
      became more impaired as task complexity increased. This study's results largely
      corroborate similar neuropsychological testing results in ADHD children and
      recent ADHD adult findings, and support a frontal lobe dysfunction hypothesis of
      ADHD.

PMID- 14590157
TI  - The impact of psychological disturbances on immediate memory.
AB  - The current study tested the hypothesis that attention mediates the impact of
      psychological disturbances (i.e. depression, loss of self-control, and bizarre
      thinking) on immediate memory. A hypothesized model, in which psychological
      disturbances indirectly impacted immediate memory via attention, was tested using
      structural equations modeling (EQS). The participants included heterogeneous
      groups of brain-damaged and psychiatric subjects both with and without age
      corrected observed variables. These groups did not vary with regard to the
      relationships within the model, and all models had good fit indices [comparative
      fit index (CFI)>0.98]. Competing models with paths directly from psychological
      disturbances to verbal, spatial, and general immediate memory were not
      significant, and these competing models did not result in a better fitting model.
      Therefore, the best fitting, most parsimonious model was the hypothesized one.
      These results corroborate the hypothesis of an indirect relationship between
      psychological disturbances and immediate memory via attention.

PMID- 14590158
TI  - Relationships among postconcussional-type symptoms, depression, and anxiety in
      neurologically normal young adults and victims of mild brain injury.
AB  - This study investigated the relationship between self-reports of postconcussional
      symptoms, depression, and anxiety in neurologically normal young adults and
      recovered victims of mild head injuries (MHI). The participants were 496 young
      adults with no history of MHI or depression, 56 neurologically normal individuals
      with clinical depression, and 40 people with history of MHI. All completed the
      Beaumont Postconcussional Index (BPCI), Beck Depression Inventory-II (BDI-II),
      and the Beck Anxiety Inventory (BAI). Groups were compared on frequency and
      severity of postconcussional symptoms, as well as general symptoms. Analysis
      revealed high correlations between scores on the Postconcussional Index (PCI) and
      the BDI-II (r=0.68) as well as between PCI and BAI (r=0.64). Correlations between
      BDI-II, BAI, and the General Symptom Index (GSI) were modest, but significant
      (r=0.44 and 0.48, respectively). MHI participants reported minimally higher
      scores on the PCI than the normative group. However, depressed individuals
      exhibited substantially higher endorsement of PCI symptoms and modestly higher
      endorsement of GSI symptoms than either the normative or MHI groups. The
      potential rule that depression can have in producing, exacerbating, and
      maintaining PCS-like symptoms must be considered when evaluating and treating
      victims of MHI.

PMID- 14590159
TI  - Neuropsychological test performance in a cognitively intact sample of older
      Japanese American adults.
AB  - The purpose of this paper was to present population-based data showing the
      effects of age on cognitive test performance in a sample of older Japanese
      American adults. In addition, the relative effects of education, gender, and
      primary spoken language were compared to effects that have been reported in the
      literature for majority culture older adults. Subjects included 201 non-demented
      Japanese American adults age 70 and older currently enrolled in the Kame Project,
      a prospective study of aging and dementia in King County, WA. Cognitive tests
      included the Consortium to Establish a Registry for Alzheimer's Disease (CERAD)
      neuropsychological assessment battery, WAIS-R Digit Span and Digit Symbol
      subtests, Trail Making Test, Purdue Pegboard, and Finger Tapping. Older age was
      associated with significantly (p<0.05) lower scores on all tests; less than high
      school education was associated with lower scores on all tests except Digit Span,
      Finger Tapping, and the Purdue Pegboard. Women and English-speaking participants
      scored higher than men and Japanese speakers on various tests of memory,
      attention, and visuomotor ability. These data reinforce the importance of using
      appropriately corrected norms when interpreting results of cognitive screening
      tests with minority culture older adults.

PMID- 14590160
TI  - Practice effects, test-retest stability, and dual baseline assessments with the
      California Verbal Learning Test in an HIV sample.
AB  - Repeated neuropsychological assessments have been recently employed to
      investigate the natural course and effects of interventions in individuals with
      human immunodeficiency virus (HIV) infection. Important considerations when
      interpreting serial assessments are the roles of practice effects and test-retest
      reliability on follow-up performance. Although several statistical and
      methodological controls have been proposed for minimizing practice effects, they
      have not been empirically tested in HIV samples. Three groups (HIV+/symptomatic,
      HIV+/asymptomatic, HIV- "at risk" controls) were administered the California
      Verbal Learning Test (CVLT) twice with a brief test-retest interval. Significant
      practice effects were observed on six of the CVLT measures. Test-retest stability
      coefficients were reported. A third and fourth administration of the CVLT was
      conducted to observe the impact of the dual baseline assessment approach on test
      performance. Trend analyses indicated that the dual baseline approach is a viable
      method for minimizing practice effects. The dual baseline approach also lead to
      improvement in a number of the stability coefficients. Limitations and future
      directions are discussed.

PMID- 14590161
TI  - A re-examination of the rate of vocational dysfunction among patients with
      anosmia and mild to moderate closed head injury.
AB  - This study sought to verify two earlier reports that up to 93% of patients with
      closed head injury (CHI) and anosmia are vocationally dysfunctional due to
      executive impairments associated with orbitofrontal damage. Participants were 11
      men and 4 women identified from a pool of 60 potential subjects referred for
      evaluation of trauma-related chemosensory dysfunction at the University of
      Pennsylvania Smell and Taste Center from 1988 to 1994. These 15 subjects met four
      criteria: (i) willingness to complete a brief semi-structured interview
      concerning their pre- and post-CHI work history; (ii) age <60 years; (iii)
      evidence of mild to moderate CHI; and (iv) scores on the University of
      Pennsylvania Smell Identification Test indicative of anosmia or severe microsmia
      and non-malingering. In contrast to the earlier reports, only 7% of the subjects
      were vocationally dysfunctional. This study calls into question previous reports
      suggesting that anosmia is a reliable predictor of post-CHI vocational outcome.

PMID- 14590162
TI  - Use of Wisconsin Card Sorting Test short forms with school-age children.
AB  - Short forms of the Wisconsin Card Sorting Test (WCST) have been developed and
      studied in adult populations, however studies addressing their use in children
      are lacking. This study compared the full WCST to two short forms in a sample of
      174 school-age children who were referred for neuropsychological evaluation.
      Multiple regression was used to predict standard scores (SSs) on the full WCST.
      Percent scores were obtained, and normative data from the WCST manual was then
      used to obtain SSs. We found that scores from the short forms were significantly
      correlated with corresponding scores on the full WCST, however a high proportion
      of children obtained short form SSs, which differed significantly from the SSs
      obtained on the full WCST. It is recommended that clinicians use the full WCST
      with children, unless at least four categories are reached in the first deck.

PMID- 14590163
TI  - Depression and the Test of Memory Malingering.
AB  - Research on the Test of Memory Malingering (TOMM) [Tombaugh, T. N., 1996. The
      Test of Memory Malingering. Toronto, Canada: Multi-Health Systems], has
      consistently shown that it is sensitive to exaggerated or deliberate faking of
      memory impairment, but it is relatively unaffected by a wide variety of
      neurological impairments causing genuine memory dysfunction. However, there is
      little research on the effects that affective disorders have on the TOMM. The
      current study examined how inpatients diagnosed with major depression performed
      on the TOMM. Results show that the TOMM is unaffected by affective state. These
      results, combined with those from previous research, provide converging evidence
      that performance on the TOMM below a cutoff score of 45 cannot be attributable to
      depression, neurological impairment, age or education.

PMID- 14590164
TI  - An evaluation of a case of agenesis of the corpus callosum with Rourke's
      nonverbal learning disorder model.
AB  - This article evaluates the case of an 11-year-old male with congenital agenesis
      of the corpus callosum, against Rourke's NLD models. A comprehensive
      neuropsychological assessment was completed, and impairments with attention,
      movement, fine motor and sensory perception, visuo-spatial organization, and
      verbal memory were identified. Additionally, a volumetric analysis of the
      magnetic resonance image (MRI) was completed. Although no gross structural
      abnormalities, beyond agenesis, were present, the possibility of unobservable
      abnormalities was considered. Many predicted NLD deficits were clearly evidenced
      in this case, including associated behavioral problems. This study concludes that
      although Rourke's NLD model is descriptive of many aspects of white matter
      impairments, it may not account for the full range or severity of deficits that
      may be observed. In callosal agenesis, children may exhibit verbal learning,
      auditory attentional, and verbal expressive difficulties.

PMID- 14590165
TI  - Do low levels of lead produce IQ loss in children? A careful examination of the
      literature.
AB  - Three meta-analyses on the relationship of low levels of lead to loss of IQ
      points in children, which included a total of 26 well-controlled studies,
      provided the raw materials for the analysis presented here. Despite some key
      limitations, results of lead-IQ studies have been instrumental in setting public
      policy. In this paper, five shortcomings in these studies are addressed, which,
      when taken together, suggest greater caution in the interpretation of the lead-IQ
      data. In addition, some other issues are addressed concerning the IQ loss
      attributed to low levels of lead.

PMID- 14590166
TI  - Methodology, inference and causation: environmental lead exposure and childhood
      intelligence.
AB  - Kaufman's critique of the literature on the associations between lead exposure
      and child intelligence raises important methodological and inferential points. We
      address the concerns he raises regarding measuring known and unknown confounders,
      statistical modeling, reverse causality and quality control. Mismeasurement of
      potential confounders of the lead-IQ relationship, such as parenting skills,
      parental intelligence, maternal smoking during pregnancy, or otitis media can
      either strengthen or weaken the estimated association between exposure and child
      intelligence. Despite some variability in design and measurement, a series of
      comprehensive prospective investigations in varied populations, by different sets
      of investigators, provided consistent replication; taken together these studies
      point to the conclusion that lead exposure has adverse consequences for child
      development, and that the deficits are likely to be small in comparison to the
      contribution of measured social factors.

PMID- 14590167
TI  - Low lead levels and neuropsychological assessment: let us not be mislead.

PMID- 14590168
TI  - Studies of lead exposure and the developing central nervous system: a reply to
      Kaufman.
AB  - Kaufman's critique of the lead-cognition hypothesis is a reiteration of well worn
      and weary claims raised many times in the past, primarily by spokespersons for
      the lead industry. They have been fully rebutted in the literature. The essence
      of these claims is that those studies showing an association between lead and IQ
      are flawed by uncontrolled confounding, multiple comparisons, and errors in
      measurement. Any effect of lead, Kaufman asserts, if present, is small. This
      response examines each of these issues and shows that they lack substance. Lead's
      negative impact on IQ persists in most modern studies after confounding has been
      controlled in many different statistical models. At least three metaanalyses have
      confirmed an effect of lead at low dose. Animal studies in which lead is given
      systematically, and the issue of confounding thereby avoided, demonstrate an
      unequivocal lead effect at similar doses to the human studies. The criticism of
      multiple comparisons similarly does not withstand examination. Measurement errors
      are nonsystematic and nondifferential. They are, therefore, null biasing. The
      actual size of the lead effect has been shown to be substantial, and to be found
      most prominently at the ends of the distribution. Kaufman says that lead requires
      study of diverse dimensions of intellect, but he restricts his scope to a sample
      of studies of lead and IQ, ignoring recent high quality studies that show a clear
      lead effect, and in those studies that he critiques he ignores data that
      contradict his position. His article adds nothing to the dialogue on lead
      neurotoxicity.

PMID- 14590169
TI  - Low-level lead exposure and intelligence in children.
AB  - Numerous prospective and cross-sectional studies of the relation between low
      level lead exposure and cognitive functioning in children have suggested that
      intellectual and academic performance declines as lead burdens increase. Kaufman
      [Arch. Clin. Neuropsychol. (2001)] raises questions regarding interpretive issues
      along these lines, and therein challenges the wisdom of using the available
      lead/IQ data complex as an essential element of the decision-making process that
      leads to policy statements. In this article, we address some of the concerns
      expressed by Kaufman, and conclude that each of his five points are logically or
      statistically flawed, as is his overall strategy of critiquing individual studies
      after methodologically sound meta-analyses have been performed. Kaufman is
      perhaps correct that the findings from correlational research on low lead levels
      and IQ loss should be interpreted with caution, but the caution extends equally
      if not more greatly in the direction of previous research having underestimated
      the relationship between the two variables in question.

PMID- 14590170
TI  - Behavioral teratology/toxicology: how do we know what we know?
AB  - Knowledge about human behavioral teratology/toxicology must necessarily be
      limited by the methods that can ethically be used. Research in the field is an
      enterprise calling for tolerance for uncertainty if not chaos. Among the main
      points of this paper are: (a) Kaufman's criticisms of research on low blood-lead
      level (BLL) and children's IQ are generally valid and apply to virtually all
      human natural-groups research; (b) Relative to some contexts, research on low BLL
      on children's IQ is exemplary; (c) Relative to other contexts, the conclusion
      that low BLL have linear effects is well supported; (d) Owing to necessary design
      limitations, all natural-groups studies have shortcomings; (e) Inference of
      causality is uncertain under any conditions; and (f) Some authors readily leap
      from molehills of data to mountains of causal conclusions.

PMID- 14590171
TI  - How dangerous are low (not moderate or high) doses of lead for children's
      intellectual development?
AB  - This paper addresses the points raised by five groups of scientists who were
      invited to respond to my article on the relationship of low blood lead to IQ
      loss. I dealt with these comments as a scientist who believes that the case is
      not closed on this topic, as some respondents believe, but that debate is healthy
      and can move the field to the next level. The criticisms about the measurement of
      parents' IQ, multiple comparisons, the linearity of the lead-IQ relationship, and
      the societal consequences of a few points of IQ loss appear weak in the face of
      an array of evidence that bears on these topics. However, criticisms about my
      emphasis on the need to control for a wide variety of potential confounders has
      validity. Ultimately, however, the case for the relationship of low blood lead to
      IQ loss seems to rest tenuously on data obtained from samples that included
      numerous subjects with moderate to severe levels of blood lead.

PMID- 14590172
TI  - Commentary on the American Academy of Neurology report on neuropsychological
      assessment.

PMID- 14590173
TI  - Neuropsychological testing of adults: further considerations for neurologists.
AB  - The recent report on neuropsychological testing of the Therapeutics and
      Technology Assessment Subcommittee of the American Academy of Neurology (AAN) has
      implications for neuropsychologists as well as neurologists. The subcommittee's
      report omits mention of standardized neuropsychological test batteries used by a
      majority of practicing neuropsychologists, and of the demonstrated validity of
      such measures for localization and lateralization of brain impairments, in
      apparent ignorance of the empirical research literature on which such
      neuropsychological examination is based. This paper elaborates the research-based
      context of neuropsychological assessment in an attempt to clarify possible false
      conclusions concerning neuropsychological assessment that could result from
      noncritical reading of the subcommittee report.

PMID- 14590174
TI  - Critical evaluation of "Assessment: neuropsychological testing of adults".
AB  - This article presents a critical evaluation of a Special Article, provided as an
      "educational service" and prepared by an Expert Panel under the direction of the
      Technology and Therapeutic Assessment Subcommittee of the American Academy of
      Neurology. The chief author of the Special Article was Jeffrey L. Cummings, M.D.

PMID- 14590175
TI  - Neuropsychological testing defines the neurobehavioral significance of
      neuroimaging-identified abnormalities.
AB  - Three cases are presented in patients all of whom sustained focal left frontal
      traumatic injury to the brain. Although each case was selected because of a
      neuroimaging-identified frontal lesion, the point is made that the behavioral
      significance of such lesions is defined by the neuropsychological examination
      process, and not the specific size, location, or type of lesion. While
      neuroimaging information is critical to the comprehensive evaluation of the
      neurologic patient, neuroimaging findings alone have only limited predictive
      ability with regard to neurobehavioral syndromes. The key role of information
      from neuropsychological test data, combined with neuroimaging findings to fully
      evaluate the neurologic patient, is made.

PMID- 14590176
TI  - Neuropsychological evaluation in rehabilitation planning and evaluation of
      functional skills.
AB  - This paper focuses on the benefits of neuropsychological assessment for
      evaluating a brain-injured person's functional abilities and rehabilitation
      needs. The importance of early assessment in addressing these goals is discussed.
      Strengths and weaknesses of neuropsychological assessment for predicting a
      person's ability to participate in normal activities of daily living are
      considered. Test data taken alone often lack ecological validity, but
      nevertheless, specific test findings can be used to predict functional skills.
      The ecological validity of neuropsychological testing can be extended by
      observing the patient's approach to tasks in the assessment environment and by
      observing the patient in his or her normal activities. Evaluation information
      obtained by allied rehabilitation professionals, including occupational and
      speech and language therapies, can be integrated with neuropsychological test
      data to both extend the generalizability of our findings and to validate
      hypotheses generated from our test data. The use of neuropsychological test data
      in planning a cognitive rehabilitation program is also considered.

PMID- 14590178
TI  - Practices in forensic neuropsychology: perspectives of neuropsychologists and
      trial attorneys.
AB  - Members of the National Academy of Neuropsychology and the Association of Trial
      Lawyers of America were surveyed concerning current practices in forensic
      neuropsychology. The majority of neuropsychologists and attorneys reported that
      attorneys never observe neuropsychological testing. Attorneys reported receiving
      raw data in almost all of their brain injury cases, but neuropsychologists
      reported that they produce raw data in only a minority of their forensic cases.
      Similarly, fewer neuropsychologists than attorneys acknowledged that they are
      asked to provide information to assist the lawyer in preparing for the cross
      examination of the opposition's expert or to prepare the plaintiff for the
      opposition's evaluation. Lawyers typically spend up to an hour preparing their
      clients for neuropsychological evaluations and commonly cover test content,
      detection of malingering, and brain injury symptoms. Other topics addressed
      include attorney influence on findings, fees and billing, board certification,
      use of technicians, and methods used to generate referrals or locate experts.
      Areas of agreement and divergence between the groups were identified and ethical
      issues raised by identified practices were examined.

PMID- 14590179
TI  - Administration duration for the Wechsler Adult Intelligence Scale-III and
      Wechsler Memory Scale-III.
AB  - The administration times for each of the subtests from the Wechsler Adult
      Intelligence Scale-III (WAIS-III) and Wechsler Memory Scale-III (WMS-III) were
      recorded for a clinical sample of 81 patients. The findings revealed that the
      time needed to administer the WAIS-III subtests to generate the summary scores,
      index scores, and both scores were 58, 51, and 65 min, respectively. The time
      required to complete the primary subtests on the WMS-III was 21, 15, and 6 min
      for Immediate Memory, General Memory, and Working Memory, respectively, resulting
      in a total administration time of 42 min. The time necessary to administer most
      of the subtests was unrelated to age, education, or performance level. These data
      demonstrate a shorter than expected administration time for the WAIS-III and a
      longer than anticipated administration for the WMS-III. Results for other
      clinical settings will be impacted by examiner familiarity and patient
      composition.

PMID- 14590180
TI  - Distinguished Neuropsychologist Award Lecture 1999. The lesion(s) in traumatic
      brain injury: implications for clinical neuropsychology.
AB  - This paper overviews the current status of neuroimaging in neuropsychological
      outcome in traumatic brain injury (TBI). The pathophysiology of TBI is reviewed
      and integrated with expected neuroimaging and neuropsychological findings. The
      integration of clinical and quantitative magnetic resonance (QMR) imaging is the
      main topic of review, but these findings are integrated with single photon
      emission computed tomography (SPECT) and magnetoencephalography (MEG). Various
      clinical caveats are offered for the clinician.

PMID- 14590181
TI  - Stability of postconcussion symptomatology differs between high and low
      responders and by gender but not by mild head injury status.
AB  - A large sample of undergraduates (N = 2,326) were screened for general health.
      The screen discretely included items assessing postconcussion symptomatology and
      neurologic history. A subsample of experiment-blind participants whose self
      reported postconcussion symptom levels were >0.5 SD below the screening sample
      mean (low symptomatic; n = 45) or >0.5 SD above the screening sample mean (high
      symptomatic; n = 53) were re-evaluated for postconcussion symptomatology 3 to 90
      days later. The sample included 50 participants who reported history of mild head
      injury (MHI) and 48 controls. MHI was defined as loss of consciousness of < or
      =20 minutes within the past 10 years, but no more recent than 3 months. Persons
      with history of >1 head injury or with other neurologic history were not included
      in the study. The stability of postconcussion symptoms differed by high
      symptomatic versus low symptomatic presentation (high symptomatic presentation
      was more variable) and by gender (females were more variable), but not by actual
      history of MHI. Sex differences in self-reported postconcussion symptomatology
      are consistent with gender-related differences in reporting of other physical and
      psychological symptoms. In addition to demonstrating differences in the stability
      of self-reported postconcussion symptomatology, the current study provides
      normative test-retest data for the Postconcussion Symptom Checklist for extreme
      responders by gender and MHI status.

PMID- 14590182
TI  - Development and initial validation of an Arabic version of the Expanded Trail
      Making Test: implications for cross-cultural assessment.
AB  - The performances of Sudanese subjects, both normal and brain damaged, on an
      Arabic version of the Expanded Trail Making Test were compared to those of normal
      and brain-damaged subjects from the United States, who completed the standard
      English version of this test. Preliminary psychometric properties of the Arabic
      version of the Expanded Trail Making Test were defined. Significant intergroup
      differences in performance were observed. Interestingly, the performances of
      Sudanese normals were found to be similar to those of U.S. brain-damaged
      subjects. The results are discussed in terms of reducing neuropsychological
      diagnostic errors attributable to ethnocultural factors.

PMID- 14590183
TI  - Exploratory factor analysis of the WAIS-III in a mixed patient sample.
AB  - The Wechsler Adult Intelligence Scale-III (WAIS-III) was administered to 152
      patients at a VA Medical Center. Means for age, education, and Full Scale IQ were
      51.49 years (SD = 13.00), 12.43 years (SD = 2.00), and 92.61 (SD = 14.06),
      respectively. Of the 152 patients, 69 had substance abuse disorders, 39 had
      medical/neurological conditions, 27 had both substance abuse and psychiatric
      disorders, and 17 had psychiatric conditions. The 13 WAIS-III subtests were
      subjected to a principal-axis factor analysis with oblimin rotation. Four factors
      were specified to be retained. The Verbal Comprehension, Perceptual Organization,
      and Processing Speed factors were identical to those in the standardization
      sample. However, Arithmetic could not be allocated to any factor within the
      patient sample. The Working Memory factor consisted only of the Digit Span and
      Letter-Number Sequencing subtests. &copy 2000 National Academy of
      Neuropsychology. Published by Elsevier Science Ltd

PMID- 14590184
TI  - Quantifying qualitative features of Block Design performance among healthy older
      adults.
AB  - Block Design tasks are neuropsychologically valuable, but standard scoring
      sacrifices potentially useful information that could elucidate the cognitive
      processes underlying performance failures. Qualitative indices that were proposed
      in the WAIS-R-NI [Kaplan, E., Fein, D., Morris, R., & Delis, D. (1991). The WAIS
      R as a neuropsychological instrument [Manual]. San Antonio, TX: Psychological
      Corporation] should help to remedy this situation but have received little
      research attention. We present WAIS-R Block Design data for 177 healthy older
      adults (aged 50-90) incorporating several qualitative measures, outlining
      normative ranges and examining age differences. Proportional scoring, counts of
      single-block placement and rotation errors, counts of parameter-violating errors
      such as breaking configuration, and availability of implicit grid information all
      offer potentially valuable supplementary data that can enrich clinical
      interpretation of Block Design protocols.

PMID- 14590185
TI  - Seatbelts contribute to location of lesion in moderate to severe closed head
      trauma.
AB  - The relationship between seatbelt use and injury severity, brain lesion location,
      and functional outcome was investigated in 163 individuals who sustained
      traumatic brain injuries in motor vehicle collisions. Of this group, 31 were
      using a seatbelt at the time of the accident and 132 were not. Restrained motor
      vehicle occupants were significantly more likely to sustain damage to subcortical
      brain structures than unrestrained occupants. Conversely, unrestrained occupants
      sustained a greater frequency of posterior brain lesions. In addition,
      demographic and behavioral variables were significantly related to increased
      likelihood of seatbelt use. Analyses revealed no significant differences between
      groups for injury severity variables and functional outcome measures. Seatbelts
      alter the body's response to forces applied in motor vehicle collisions, creating
      disparities in lesion sites between restrained and unrestrained motor vehicle
      occupants. The relationship between seatbelt use and injury severity and
      functional outcome is discussed.

PMID- 14590186
TI  - Interpreting change on the WAIS-III/WMS-III in clinical samples.
AB  - Clinicians should note that there is considerable variability in the
      reliabilities of the index and subtest scores derived from the third editions of
      the Wechsler Adult Intelligence Scale (WAIS-III) and the Wechsler Memory Scale
      (WMS-III). The purpose of this article is to review these reliabilities and to
      illustrate how they can be used to interpret change in patients' performances
      from test to retest. The WAIS-III IQ and Index scores are consistently the most
      reliable scores, in terms of both internal consistency and test-retest
      reliability. The most internally consistent WAIS-III subtests are Vocabulary,
      Information, Digit Span, Matrix Reasoning, and Arithmetic. Information and
      Vocabulary have the highest test-retest reliability. On the WMS-III, the Auditory
      Immediate Index, Immediate Memory Index, Auditory Delayed Index, and General
      Memory Index are the most reliable, in terms of both internal consistency and
      test-retest reliability. The Logical Memory I and Verbal Paired Associates I
      subtests are the most reliable. Data from three clinical groups (i.e.,
      Alzheimer's disease, chronic alcohol abuse, and schizophrenia) were extracted
      from the Technical Manual [Psychological Corporation (1997). WAIS-III/WMS-III
      Technical Manual. San Antonio: Harcourt Brace] for the purpose of calculating
      reliable change estimates. A table of confidence intervals for test-retest
      measurement error is provided to help the clinician determine if patients have
      reliably improved or deteriorated on follow-up testing.

PMID- 14590188
TI  - Evaluation of seven-subtest short forms of the Wechsler Adult Intelligence Scale
      III in a referred sample.
AB  - The application of seven-subtest short forms of the Wechsler Adult Intelligence
      Scale-III (WAIS-3) was evaluated in a sample of 281 mixed clinical patients from
      three Veterans Affairs Medical Centers. Short-form summary scores were derived
      from deviation quotient tables and from prorating. They included either Block
      Design or Matrix Reasoning. Short-form summary scores for Full-Scale IQ (FSIQ)
      and Verbal IQ (VIQ) demonstrated good alternate-forms reliability with the full
      WAIS-3 scores, whereas Performance IQ (PIQ) summary scores were less accurate.
      Short forms derived from deviation quotients and prorating did not differ from
      each other. However, the inclusion of Matrix Reasoning resulted in somewhat
      better accuracy with WAIS-3 PIQ than did Block Design. The results of this study
      support the use of the seven-subtest short form of the WAIS-3 in estimating full
      WAIS-3 summary scores, especially for FSIQ and VIQ.

PMID- 14590189
TI  - Serial neuropsychological assessment with the National Institute of Mental Health
      (NIMH) AIDS Abbreviated Neuropsychological Battery.
AB  - The effect of repeated administration of the (NIMH) AIDS Abbreviated
      Neuropsychological Battery was evaluated in a group of "at risk" individuals who
      served as control subjects in a larger research project. Subjects' performance
      across five assessment points was evaluated by repeated measures analysis.
      Statistically significant trends were obtained on the California Verbal Learning
      Test, the Paced Auditory Serial Addition Task, and the State scale of the State
      Trait Anxiety Inventory. No discernable trends were detected on the Vocabulary
      subtest of the Wechsler Adult Intelligence Scale-Revised, total time or errors on
      the Visual Search Task, the Hamilton Depression Rating Scale, or the Trait scale
      of the State-Trait Anxiety Inventory. The implications of these findings in both
      clinical and research settings are discussed.

PMID- 14590190
TI  - Neuropsychological profiles associated with subcortical white matter alterations
      and Parkinson's disease: implications for the diagnosis of dementia.
AB  - Despite the emergence of a number of new classification systems, the diagnosis of
      cerebrovascular dementia remains controversial. Also controversial is the
      significance of periventricular and deep white matter alterations (WMA) as seen
      on magnetic resonance imaging (MRI). To further clarify this issue, MRI scans
      were used to regroup patients clinically diagnosed with Alzheimer's disease (AD)
      or subcortical ischemic vascular dementia (IVD) into cohorts presenting with
      either little versus significant WMA on MRI. These two groups were then compared
      to demented patients diagnosed with idiopathic Parkinson's disease (PD) using a
      comprehensive neuropsychological protocol. Neuropsychological assessment failed
      to distinguish between patients with PD and significant WMA. By contrast, both of
      these patient groups exhibited disproportionate impairment on tests of executive
      systems functioning, whereas patients with little WMA showed greater impairment
      on tests of declarative memory and semantic knowledge. These findings constitute
      further evidence that the pattern of cognitive impairment associated with
      significant WMA is distinctly different when compared to AD. These results are
      discussed within the context of a growing body of literature suggesting that
      elements of the underlying neuropathologies in AD and IVD are linked.
      Implications for the diagnosis of dementia are also discussed.

PMID- 14590191
TI  - A case of claimed persistent neuropsychological sequelae of chronic formaldehyde
      exposure: clinical, psychometric, and functional findings.
AB  - Many anecdotal cases and some clinical studies have demonstrated that
      formaldehyde exposure can cause multiple health-related problems and cerebral
      dysfunction. The U.S. Consumer Product Safety Commission has documented multiple
      hazards related to formaldehyde exposure. Some of this research has suggested
      that low levels of exposure can be very hazardous to one's health and can
      potentially result in heightened chemical sensitivities, seizures, and cognitive
      decline. Some research suggests that exposure results in long-term immunological
      changes, cell neurofilament protein changes, and demyelination. Symptomatically,
      exposure has been associated with respiratory problems, excessive fatigue,
      headaches, mood changes, and impaired attention, concentration, and memory
      functioning. This article outlines the case of a biology teacher whose chronic
      formaldehyde exposure resulted in heightened sensitivity to formaldehyde, three
      tonic-clonic seizures, and dramatic amnesia as well as other cognitive
      dysfunction.

PMID- 14590192
TI  - Detection of inadequate effort on neuropsychological testing: a meta-analytic
      review of selected procedures.
AB  - Thirty-two studies of commonly researched neuropsychological malingering tests
      were meta-analytically reviewed to evaluate their effectiveness in discriminating
      between honest responders and dissimulators. Overall, studies using the Digit
      Memory Test (DMT), Portland Digit Recognition Test (PDRT), 15-Item Test, 21-Item
      Test, and the Dot Counting Test had average effect sizes indicating that
      dissimulators obtain scores that are approximately 1.1 standard deviations below
      those of honest responders. The DMT separated the means of groups of honest and
      dissimulating responders by approximately 2 standard deviations, whereas the 21
      Item Test and the PDRT separated the groups by nearly 1.5 and 1.25 standard
      deviations, respectively. The 15-Item Test and the Dot Counting Test were less
      effective, separating group means by approximately 3/4 of a standard deviation.
      Although the DMT, PDRT, 15-, and 21-Item Tests all demonstrated very high
      specificity rates, at the level of individual classification, the DMT had the
      highest sensitivity and overall hit-rate parameters. The PDRT and 15-Item Test
      demonstrated moderate sensitivity, whereas the 21-Item Test demonstrated poor
      sensitivity. The less than perfect sensitivities of all the measures included in
      this review argue against their use in isolation as malingering screening
      devices.

PMID- 14590193
TI  - Detecting change: A comparison of three neuropsychological methods, using normal
      and clinical samples.
AB  - Detecting change in individual patients is an important goal of
      neuropsychological testing. However, limited information is available about test
      retest changes, and well-validated prediction methods are lacking. Using a large
      nonclinical subject group (N = 384), we recently investigated test-retest
      reliabilities and practice effects on the Wechsler Adult Intelligence Scale and
      Halstead-Reitan Battery. Data from this group also were used to develop models
      for predicting follow-up test scores and establish confidence intervals around
      them. In this article we review those findings, examine their generalizability to
      new nonclinical and clinical groups, and explore the sensitivity of the
      prediction models to real change. Despite similarities across samples in
      reliability coefficients and practice effects, limits to the generalizability of
      prediction methods were found. Also, when multiple test measures were considered
      together, one or more "significant" changes were common in all (including stable)
      subject groups. By employing normative cut-offs that correct for this,
      sensitivity of the models to neurological recovery and deterioration was modest
      to good. More complex regression models were not more accurate than the simpler
      Reliable Change Index with correction for practice effects when confidence
      intervals for all methods were adjusted for variations in level of baseline test
      performance.

PMID- 14590195
TI  - Stereoscopic visual impairment in vascular dementia.
AB  - Binocular depth perception is mediated by neural pathways that involve thalamic
      nuclei, the posterior parietal lobe and adjacent gyri, and white matter
      projections connecting these regions. Vascular dementia results from a variety of
      pathologic syndromes that can affect these areas, and in the current study is
      shown to produce associated impairment of stereoacuity or complete
      stereoblindness. Stereoacuity was relatively more impaired by right than left
      hemisphere pathology, by cortical than subcortical vascular processes, and by
      lesions that involved the parietal lobe. The extent of impairment was related to
      dementia severity as reflected by measures of intelligence, memory, and visual
      spatial function. Stereoacuity was unimpaired in age-matched patients with
      depressive disorders.

PMID- 14590196
TI  - Color-to-figure matching in Alzheimer's disease.
AB  - Thirty-three patients with probable Alzheimer's disease were examined on a
      standardized Color-to-Figure Matching Test (CFMT) for which patients select
      appropriate colors from a set of colored pencils to match outline pictures of
      common objects. Seven patients performing below the CFMT cut-off score were
      further assessed using other tests investigating the naming of these outline
      pictures of common objects as well as the naming and sorting of colors: One
      patient performed badly in all tests; three other patients could not be
      considered true cases of poor object-color retrieval because of their inability
      to name the objects; and in the remaining three patients with unimpaired object
      naming (although two of them had word-finding difficulties), their impaired
      object-color retrieval was found to dissociate from both color sorting and color
      naming. These findings support the notion of a separation of pure color
      processing from object-color knowledge. Thus for patients with Alzheimer's
      disease, there is evidence in a few instances for a dissociation between object
      color retrieval and both color sorting and color naming.

PMID- 14590197
TI  - Subject-selection procedures in neuropsychological research: a meta-analysis and
      prospective study.
AB  - The present study examined methods of control- and experimental-subject selection
      in neuropsychological research. Using both meta-analytic and prospective
      procedures, it was found that varied subject-selection procedures can potentially
      confound the results of neuropsychological studies and, by extension, can thwart
      the formulation of laws regarding neuropsychological function. In terms of
      selecting control subjects, the current findings suggest that individuals who
      self-report a negative history for neuropathology and psychopathology are
      adequate, perhaps even preferable, for inclusion. In terms of selecting
      experimental subjects, it appears preferable, if not essential, to obtain lesion
      confirmation through relevant neurodiagnostic tests. Based on these findings, it
      is recommended that subject selection be made on the basis of scientific merit
      rather than convenience or availability.

PMID- 14590198
TI  - Neuropsychological, neuroanatomical, and neurophysiological consequences of CNS
      chemotherapy for acute lymphoblastic leukemia.
AB  - Medical treatment for acute lymphoblastic leukemia (ALL) has improved survival
      rates to 70% for children currently diagnosed with this disease. Intrathecal (IT)
      chemotherapy replaced CNS radiation therapy (CRT) for those with a favorable
      diagnosis as research revealed cognitive deficits associated with CRT. The
      literature pertaining to the potential adverse intellectual and
      neurophysiological consequences of IT chemotherapy is reviewed. It is concluded
      that IT chemotherapy may not be a benign form of treatment, although its effects
      may be more subtle than those produced by CRT. Future studies implementing more
      comprehensive test batteries are needed to illuminate these deficits so that
      remediation may be possible for ALL survivors.

PMID- 14590199
TI  - Constructs underlying measures of sensory-motor functions.
AB  - Many pathognomonic indicators of brain damage are characterized by deficits in
      sensory and/or motor functions. The strength of these pathognomonic signs has led
      to reliance on clinical administration and interpretation in the assessment of
      sensory and motor functions. Subsequently, the majority of measures designed to
      assess sensory and motor functions lack adequate reliability and psychometric
      confirmation of their utility. The Dean-Woodcock Sensory-Motor Battery (DWSMB)
      was designed to standardize the administration and interpretation of sensory
      motor functions and has demonstrated satisfactory reliability. The present study
      further examined the psychometric properties of the DWSMB through factor
      analysis. It was hypothesized that at least two factors would emerge representing
      sensory and motor functions, respectively. A third possible factor that would
      reflect subcortical functioning was also hypothesized. Principal components
      analysis on data from over 600 participants supported a three-factor solution
      which accounted for 50.9% of the total variance. However, factor loadings
      revealed more dual loadings than expected, and factors emerged according to
      complexity rather than basic sensory, motor, and subcortical factors. Regardless,
      these data provide empirical evidence for the conceptualization of sensory-motor
      skills in a manner that incorporates subcortical abilities. These data also
      provide support for the underlying constructs of the DWSMB.

PMID- 14590200
TI  - Does brief loss of consciousness affect cognitive functioning after mild head
      injury?
AB  - Loss of consciousness often is considered an important variable when estimating
      head injury severity. The purpose of this study was to determine if brief loss of
      consciousness had any effect on the neuropsychological test performance of
      patients in acute recovery from an uncomplicated mild head injury (N = 195).
      Three groups of 65 patients were given a brief battery of neuropsychological
      tests within one week of sustaining a mild head injury. The groups, sorted on the
      basis of loss of consciousness (i.e., positive, negative, or equivocal), did not
      differ in age or education. There were no significant differences among the
      groups on any of the measures of attention, learning, memory, language, or
      executive functioning.

PMID- 14590202
TI  - The use of significant others to enhance the detection of malingerers from
      traumatically brain-injured patients.
AB  - Cognitive and neurobehavioral symptoms are common following traumatic brain
      injuries (TBIs). Because malingerers are likely to complain of such symptoms and
      perform poorly on neuropsychological tests, clinicians may have considerable
      difficulty distinguishing malingerers from TBI patients. In this study, we
      compared the subjective complaints of malingerers to TBI patients and then
      compared both groups to the problems observed by their respective significant
      others. We tested the assumption whether significant others could add one more
      piece to the challenging puzzle of diagnosing malingering. Our results
      demonstrated that the malingerers complained of more problems than patients who
      had sustained moderate or severe TBI. However, the significant others of the
      malingerers observed fewer cognitive, emotional-behavioral, and total problems
      than did the significant others of patients with severe, moderate, and even mild
      TBI. These findings suggest that the detection of malingering can be enhanced by
      interviews with significant others.

PMID- 14590203
TI  - Aging and word-finding: a comparison of spontaneous and constrained naming tests.
AB  - This study compared the word-finding abilities of 26 young adults (ages 18-22
      years), 26 young-old adults (ages 58-74 years), and 26 old-old adults (ages 75-93
      years) on a confrontational naming test (Boston Naming Test) and a more
      spontaneous discourse test. The groups were matched in terms of gender (7 male,
      19 female) and estimated IQ (M = 114). When participants were asked to narrate
      what they perceived in pictures (discourse test), the older adult groups
      committed significantly more word-retrieval errors than the younger adults. In
      contrast, results from the picture-naming test surprisingly revealed higher
      naming accuracy by the older adult groups. Subsequent examination of the picture
      naming items revealed that four items appeared to be influenced by generational
      familiarity with the item. These results suggest that selection of cohort-free
      items for picture-naming tests is important when comparing across age-groups, and
      that tests of discourse may be better measures for assessing everyday word
      finding difficulties in healthy older adults.

PMID- 14590204
TI  - Age-related cognitive decline during normal aging: the complex effect of
      education.
AB  - The purpose of this study was to further analyze the effects of education on
      cognitive decline during normal aging. An 806-subject sample was taken from five
      different Mexican regions. Participants ranged in age from 16 to 85 years.
      Subjects were grouped into four educational levels: illiterate, 1-4, 5-9, and 10
      or more years of education, and four age ranges: 16-30, 31-50, 51-65, and 66-85
      years. A brief neuropsychological test battery (NEUROPSI), standardized and
      normalized in Spanish, was administered. The NEUROPSI test battery includes
      assessment of orientation, attention, memory, language, visuoperceptual
      abilities, motor skills, and executive functions. In general, test scores were
      strongly associated with level of educational, and differences among age groups
      were smaller than differences among education groups. However, there was an
      interaction between age and education such as that among illiterate individuals
      scores of participants 31-50 years old were higher than scores of participants 16
      30 years old for over 50% of the tests. Different patterns of interaction among
      educational groups were distinguished. It was concluded that: (a) The course of
      life-span changes in cognition are affected by education. Among individuals with
      a low level of education, best neuropsychological test performance is observed at
      an older age than among higher-educated subjects; and (b) there is not a single
      relationship between age-related cognitive decline and education, but different
      patterns may be found, depending upon the specific cognitive domain.

PMID- 14590205
TI  - Neuropsychological profile of a large kindred with familial Alzheimer's disease
      caused by the E280A single presenilin-1 mutation.
AB  - It was hypothesized that subjective memory complaints represent the earliest sign
      of dementia in carriers of the presenilin-1 (PS1) mutation. A total of 122
      subjects (44 males, 78 females) were included in this study. Forty of them were
      positive for the mutation in the PS1 gene (mutation positive, MP) whereas 82
      showed negative results (mutation negative, MN). Subjects were active,
      functionally normal, even though some of them complained of memory difficulties.
      Two groups of neuropsychological instruments were administered: (a) The
      Consortium to Establish a Registry for Alzheimer's Disease (CERAD)
      neuropsychological test battery (Morris et al., 1989), and (b) some additional
      neuropsychological tests (Raven Test, Wechsler Memory Scale, Rey-Osterrieth
      Complex Figure, Boston Naming Test, Naming of Categories, Boston Diagnostic
      Aphasia Examination, Memory of Three Phrases, Knopman Test, Digit Symbol, and
      Visual "A" Cancellation Test). Performance in both groups was quite similar. In a
      secondary analysis, the MP group was subdivided into two subgroups: without and
      with memory complaints. When comparing both subgroups, a better performance in
      the first subgroup was found throughout the different subtests. Statistically
      significant differences were observed in the following test scores: Mini-Mental
      State Examination, Naming Test (Low Frequency), Memory of Words Test, Recall of
      Drawings, Wechsler Memory Scale (Logical Memory, Associative Learning, and Total
      Score), Rey-Osterrieth Complex Figure (Immediate Recall Condition), Boston
      Diagnostic Aphasia Examination (Complex Ideational Material Subtest), Memory of
      Three Phrases Test, Serial Verbal Learning (maximum score and Delayed Recall),
      Knopman Test (First Trial, Second Trial, and Recall after 5 Minutes), Digit
      Symbol, and Visual "A" Cancellation Test (Additions). Results supported the
      hypothesis that memory complaints represent the earliest symptom of familial
      Alzheimer's disease. In addition to the memory difficulties, other minor
      cognitive impairments were also found, particularly, mild anomia, concentration
      difficulties and defects in the understanding of complex verbal material.

PMID- 14590206
TI  - Sensitivity of category cued recall to very mild dementia of the Alzheimer type.
AB  - We sought to replicate Buschke, Sliwinski, Kulansky, and Lipton's (1997) finding
      that the Category Cued Recall portion of the Double Memory Test can discriminate
      individuals with mild dementia of the Alzheimer type (DAT) and healthy older
      controls. We then attempted to extend this finding to those with very mild DAT.
      Finally, we compared these results with those of other tests that discriminate
      DAT from normal aging. Although we replicated Buschke et al.'s finding that the
      Category Cued Recall portion of the Double Memory Test discriminates effectively
      between mildly demented people and controls, it was little more effective in
      detecting very mild DAT than the WMS Logical Memory subtest nor did it add
      substantially to the discriminative ability of a brief battery of psychometric
      tests identified previously.

PMID- 14590207
TI  - Impact of human immunodeficiency virus type-1-associated cognitive dysfunction on
      activities of daily living and quality of life.
AB  - We examined the impact of neuropsychological (NP) impairment on activities of
      daily living (ADLs) and quality of life in human immunodeficiency virus type-1
      (HIV-1)-infected persons of low socioeconomic status (SES). Thirty-nine patients
      were stratified into one of three groups: cognitively normal (n = 13), mild
      cognitive impairment (n = 15), and moderate/severe impairment (n = 11). Quality
      of life was assessed with the Sickness Impact Profile and ADLs were evaluated via
      structured interview performed in the patient's residence. While there were no
      significant differences across groups on disease stage, drug use, depression, or
      estimated premorbid IQ, cognitively impaired patients were more likely to be
      unemployed and fail social planning and medication management tasks. Our study
      confirms a previously reported association between NP impairment and unemployment
      among HIV-1-infected patients. The data also extend this relationship to a low
      SES sample with a high base rate of unemployment, and to instrumental activities
      of daily living other than work.

PMID- 14590208
TI  - Quantitative PET scan findings in carbon monoxide poisoning: deficits seen in a
      matched pair.
AB  - Quantitative positron emission tomography (PET) was utilized to establish the
      degree and localization of central nervous system dysfunction in 2 adult patients
      3 years status postchronic carbon monoxide poisoning. The individual PET scans
      were compared against a composite scan made up of 32 normals using a z
      transformation statistical parametric map. Neuropsychological findings indicated
      marked anterior frontal lobe syndrome in the context of far-above-average
      intelligence, memory, and language. They also showed manifest frontal symptoms in
      activities of daily living that resulted in vocational disability in each case.
      PET analysis revealed substantially decreased metabolism in the orbitofrontal and
      dorsolateral prefrontal cortex as well as in areas of the temporal lobe for each
      individual. Individual scans were very similar and consistent with patient's
      presenting symptoms, and changed life circumstances. This report represents the
      first quantitative functional neuroimaging study relevant to carbon monoxide
      poisoning.

PMID- 14590212
TI  - Presence of third party observers during neuropsychological testing: official
      statement of the National Academy of Neuropsychology. Approved 5/15/99.

PMID- 14590213
TI  - The use of neuropsychology test technicians in clinical practice: official
      statement of the National Academy of Neuropsychology. Approved 5/15/99.

PMID- 14590214
TI  - Test security: official position statement of the National Academy of
      Neuropsychology. Approved 10/5/99.

PMID- 14590215
TI  - Neurovegetative symptoms in multiple sclerosis: relationship to depressed mood,
      fatigue, and physical disability.
AB  - Some authors have suggested that when evaluating depression in multiple sclerosis
      (MS) patients, neurovegetative symptoms should be discounted and/or not
      considered, given the ostensibly high overlap between symptoms of MS (e.g., sleep
      disturbance, fatigue) and neurovegetative symptoms of depression. A further
      assertion is that inclusion of items assessing neurovegetative symptoms may
      artificially inflate overall depression scores and that mood scales may provide
      more accurate indices of depression in MS patients. The current study
      investigated the possibility that some neurovegetative symptoms may be
      specifically related to MS patients' depressed mood and are not simply indicators
      of physical disability and/or fatigue. Seventy-six clinically definite MS
      patients in the northwestern United States were administered two depression
      inventories and measures of physical disability and fatigue as part of a larger
      study. Results revealed that one neurovegetative symptom--disinterest in sex--was
      uniquely associated with depressed mood, and other neurovegetative symptoms were
      associated with both depression and fatigue but not physical disability. The
      present findings suggest that certain neurovegetative symptoms are differentially
      associated with depression, fatigue, and physical disability in MS. Routinely
      discounting all neurovegetative symptoms when assessing depression in MS patients
      may thus be unwarranted.

PMID- 14590216
TI  - Effects of coaching on detecting feigned cognitive impairment with the Category
      test.
AB  - In a replication and extension of previous research (Tenhula & Sweet, 1996), the
      current study investigated the utility of the Category Test (CT) for detecting
      feigned cognitive impairment. Ninety-two undergraduate participants were randomly
      assigned to one of three groups and administered the CT. A Coached Simulator
      group was instructed to simulate cognitive impairment and was provided test
      taking strategies to avoid detection. An Uncoached Simulator group was simply
      instructed to feign impairment. A control group was instructed to perform
      optimally. In addition, the CT results of 30 traumatic brain injury (TBI)
      patients were analyzed. The results largely supported the utility of five CT
      malingering indicators identified by Tenhula and Sweet: (a) number of errors on
      subtests I and II, (b) number of errors on subtest VII, (c) total CT errors, (d)
      number of errors on 19 "easy" items, and (e) number of criteria exceeded. Correct
      Classification rates of the five indicators for Uncoached Simulators and optimal
      performance controls ranged from 87% to 98%. Correct Classification rates for the
      TBI patients ranged from 70% to 100%. In addition, significantly more Coached
      Simulators were misclassified as nonsimulators on four of the CT malingering
      indicators, relative to their Uncoached counterparts. A decision rule of > 1
      error on subtests I and II was consistently the most accurate malingering
      indicator, regardless of degree of coaching or presence of TBI. This indicator
      correctly classified 76% of all simulators and 100% of the optimal performance
      controls and TBI patients. Implications of providing persons with test-taking
      strategies and the utility of these CT malingering indicators for various
      populations are discussed.

PMID- 14590217
TI  - The effects of coaching on the sensitivity and specificity of malingering
      measures.
AB  - This study sought to identify patterns of performance indicative of malingering
      on the Auditory Verbal Learning Test (AVLT). Participants were randomly assigned
      to perform normally, simulate head injury, or simulate head injury with warning
      that there might be attempts to detect malingering. Participants completed an
      expanded AVLT and a forced-choice task, in addition to several other memory
      tests. The warned simulators performed worse than normals on the forced-choice
      task, but better than those simulating head injury without a warning, suggesting
      that the warned subjects recognized forced choice as a malingering test. A
      combination of AVLT indices was able to predict group status for both nai;ve and
      warned malingerers (73.6% for nai;ve malingerers, 84.8% for warned, no false
      positives). The forced-choice measure detected only 31.6% of the nai;ve
      malingerers when specificity was maximized, and detected only 6.5% of the warned
      malingerers, a significant drop in detection rate. Findings suggest that pattern
      of performance indices are useful in detecting malingering, even when subjects
      are aware of attempts to detect malingering.

PMID- 14590218
TI  - Equivalence of the Color Trails Test and Trail Making Test in nonnative English
      speakers.
AB  - The Color Trails Test (CTT) has been described as a culture-fair test of visual
      attention, graphomotor sequencing, and effortful executive processing abilities
      relative to the Trail Making Test (TMT). In this study, the equivalence of the
      TMT and the CTT among a group of 64 bilingual Turkish university students was
      examined. No difference in performance on the CTT-1 and TMT Part A was found,
      suggesting functionally equivalent performance across both tasks. In contrast,
      the statistically significant differences in performance on CTT-2 and TMT Part B,
      as well as the interference indices for both tests, were interpreted as providing
      evidence for task nonequivalence of the CTT-2 and TMT Part B. Results have
      implications for both psychometric test development and clinical cultural
      neuropsychology.

PMID- 14590219
TI  - The neuropsychological similarities of mild and more severe head injury.
AB  - Reports in the literature have suggested that the neuropsychological effects of
      mild head injury are selective, represented by impairment of attention,
      information processing, and memory, and that evaluations with comprehensive and
      standard test batteries are likely to miss such deficits. The present study
      compared groups of individuals with mild head injuries, more severe head
      injuries, and non-brain-damaged controls using 19 tests from the Halstead-Reitan
      Battery. The results indicated that the group with mild head injuries performed
      significantly poorer than the controls, and that the group with more severe head
      injuries scored significantly more poorly than either of the other groups.
      Comparisons of the pattern of test scores for the two head-injured groups were
      remarkably similar across the 19 tests, yielding a rank difference correlation of
      0.87. The findings yielded no evidence of selective or delimited impairment in
      the group with mild head injuries, but instead, showed them to have test results
      that were very similar, though showing less neuropsychological impairment, to the
      group of subjects with more severe head injuries. These findings suggest that a
      comprehensive neuropsychological test battery is necessary to detect the broad
      range of deficits that may result from mild head injury.

PMID- 14590220
TI  - Conation: a neglected aspect of neuropsychological functioning.
AB  - Conation, which involves the ability to apply oneself diligently and productively
      to the completion of a task over time, was compared in groups with and without
      evidence of brain damage. Both groups were administered tests that ranged from
      tasks that were presented by an examiner one item at a time (minimal conation),
      to a task that required the subject to work independently for 30 minutes, with
      instructions to work as quickly and as accurately as possible. In this study it
      was not possible to control test content perfectly, but all tasks were primarily
      verbal in nature. The subjects with brain damage, compared to the controls,
      showed progressive impairment in accordance with the degree to which the tasks
      were judged to require conative ability. Conation, which has been a neglected
      dimension of behavior in neuropsychological assessment, may be the missing link
      between cognitive ability and prediction of performance capabilities in everyday
      life. Additional research is needed to investigate further this apparently
      significant aspect of neuropsychological functioning.

PMID- 14590225
TI  - Performance curve classification of invalid responding on the Validity Indicator
      Profile.
AB  - The purpose of this article is to provide evidence for the validity of
      performance curve classification on the nonverbal subtest of the Validity
      Indicator Profile (VIP-NV). A four-fold classification scheme of performance on
      cognitive testing is proposed. This scheme combines effort and motivation to
      generate four response classifications: compliant, careless, irrelevant, and
      malingering. Data are presented across six studies from cognitive and personality
      testing for 737 male pretrial criminal defendants. Additionally, computer
      generated VIP-NV performances were subjected to four levels of randomization to
      investigate VIP-NV carelessness indicators. The findings support the validity of
      the four-fold classification scheme and support the classification of response on
      the basis of motivation and effort.

PMID- 14590226
TI  - Diagnostic efficiency and material specificity of the Warrington Recognition
      Memory Test: a collaborative multisite investigation.
AB  - Two studies examined the Warrington Recognition Memory Test (RMT) discrepancy
      index (Words-Faces) in a large sample of patients heterogeneous with respect to
      age, education, gender, and neurological diagnosis. In Study 1 (N = 504) we used
      cutoffs from the Words-Faces discrepancy scores derived from Warrington's
      original validation sample to attempt to accurately classify patients with left,
      right, or diffuse brain damage. Sensitivity for left hemisphere patients (Faces >
      Words) was 10% with a specificity of 88%, whereas sensitivity for right
      hemisphere patients (Words > Faces) was 48% with a specificity of 86%. For
      patients with diffuse brain damage (Words = Faces) sensitivity was 69% and
      specificity was 38%. In Study 2 (N = 263), we examined the relationship between
      the Words-Faces discrepancy score and Wechsler Memory Scale-Revised (WMS-R;
      Wechsler, 1981) Logical Memory and Visual Reproduction subtests. Contrary to
      predictions, patients with Words > Faces performed better on both WMS-R subtests;
      the Faces > Words discrepancy was not related to Visual Reproduction performance.
      Potential reasons for these negative findings are discussed, as well as cautions
      for future RMT discrepancy index use.

PMID- 14590227
TI  - Age effects on Wechsler Adult Intelligence Scale-III subtests.
AB  - This investigation extended work on the Wechsler Adult Intelligence Scaled
      Revised (WAIS-R) to the WAIS-III by determining how allotments of scaled-score
      points change with age, and to evaluate WAIS-III performance in terms of the Horn
      Cattell constructs of crystallized and fluid intelligence. The age norms for the
      14 individual WAIS-III subtests indicate that additional scaled-score points are
      awarded primarily to the Letter-Number Sequencing subtest of the Verbal Scale and
      to the seven Performance Scale subtests at ages 45 to 89 years for the same
      performance as individuals in the 20- to 34-year-old reference group. Subtests
      that measure speed of information processing showed more of a decline than
      subtests that measure verbal processing. Results are consistent with the view
      that measures of fluid intelligence show more of a decline with advancing age
      than do measures of crystallized intelligence. Published by Elsevier Science Ltd

PMID- 14590228
TI  - Spot-the-Word: a measure for estimating premorbid intellectual functioning.
AB  - The present study investigates the validity of a recently developed measure for
      estimating premorbid cognitive abilities. The Spot-the-Word Test involves
      presenting participants with pairs of items comprised of one word and one
      nonword, and requiring the subject to identify the word. Participants were 61
      community-residing healthy older adults ranging in age from 60 to 91 years.
      Results indicated that education had a small but significant effect on Spot-the
      Word performance. However, gender and age did not. Significant correlations were
      observed between Spot-the-Word scores and scores on other measures used to
      estimate premorbid abilities, suggesting adequate convergent validity.
      Furthermore, small and nonsignificant correlations were observed between Spot-the
      Word scores and sensitive neuropsychological variables suggesting adequate
      discriminant validity. Recommendations for future research are discussed.

PMID- 14590229
TI  - A comparison of self- and other-rated forms of the neuropsychology behavior and
      affect profile in a traumatic brain injury population.
AB  - The current study is the first reported use of both the other-rated and the self
      rated forms of the Neuropsychology Behavior and Affect Profile (NBAP; Nelson,
      Satz, & D'Elia, 1994). Twenty-eight adult patients who were 7 to 27 months post
      predominantly mild closed head injury completed the self-report form of the NBAP,
      and their identified relatives/close friends completed the other-rated form of
      the NBAP. Patients and their relatives endorsed more items on the
      Inappropriateness and Depression scales for "now," as compared to "before" the
      injury. Only the patients endorsed more items on the Pragnosia scale for "now" as
      compared to "before." Comparisons of the NBAP pairs found no significant
      differences between the patients' self-reports and those of their significant
      others for "before" the injury. Patients endorsed more items on the Indifference
      and Pragnosia scales for "now," as compared to their relatives.

PMID- 14590230
TI  - The effects of two motivational manipulations on the neuropsychological
      performance of mildly head-injured college students.
AB  - Recently, much research has focused on the development and utilization of various
      motivational assessment techniques designed to identify malingered
      neuropsychological test performance. Other findings have suggested a strong link
      between the motivation of the subject and the degree to which the
      neuropsychological test results validly represent the individual's true level of
      functioning. However, the majority of the empirical work in this area has focused
      on only one end of the motivational spectrum, decreased motivation. In order to
      obtain a more complete assessment of the relationship between motivation and
      neuropsychological of test results, the present study involved an evaluation of
      the effects of motivational differences on test performance across three levels
      of motivation: high, low, and standard in 75 head-injured college students.
      Results supported past research showing significant decreases in test performance
      by participants given individual financial incentives (25.00 US dollars) to
      perform poorly. Additionally, the sensitivity of several malingering tests to
      this response set was supported. However, no reliable differences were found on
      neuropsychological or motivational tests between the group given financial
      incentives (25.00 US dollars) to perform well and the standard instruction group.

PMID- 14590231
TI  - Have we forgotten the base rate problem? Methodological issues in the detection
      of distortion.
AB  - The search for valid and reliable methods of detecting malingering and distortion
      has become an increasingly important task for forensic psychologists and
      neuropsychologists. This report highlights several important methodological
      issues commonly observed in research on the prediction of malingering. The choice
      of indices for determining optimal cutoff scores on the utility of existing
      measures, the impact of base rates of malingering on the accuracy of prediction
      models, the incremental accuracy of combining multiple measures, and the
      relationship of test validity to the interpretation of data are described with
      regard to the prediction of malingering on neuropsychological tests. These
      methodological concerns are discussed in reference to several recent publications
      assessing the utility of various methods for the detection of malingering.

PMID- 14590232
TI  - Recall and recognition in Huntington's disease.
AB  - We assessed 19 patients with Huntington's disease (HD) at early to moderately
      advanced stages of their disease using memory tests that investigated verbal and
      visual recall and recognition. In those tests where identical material was
      subject to recall and recognition the standardized results (z scores) were lower
      for recognition. Performance was better with pictorial than with verbal material.
      While recognition bias and savings scores did not differ significantly from
      controls, all other recognition parameters did so. This is in contrast to the
      claim that defective retrieval in HD is greatly enhanced by multiple choice
      recognition. One major reason for maintaining this assumption was apparently the
      disregard of false-positive responses. Our results indicate that verbal and
      visual recognition are impaired in HD, and the notion of a salient deficit of
      free recall is not supported.

PMID- 14590548
TI  - The ecological validity of clinical tests of memory and attention in multiple
      sclerosis.
AB  - Ecological validity--the degree to which clinical tests of cognitive functioning
      predict functional impairment--has recently become an area of interest in
      neuropsychology. The current study used a sample of 31 cognitively and
      functionally impaired multiple sclerosis (MS) patients to determine if tests
      commonly used to assess memory and attentional functioning in MS are ecologically
      valid. Two methods of improving the ecological validity of cognitive testing were
      employed. Stepwise multiple regression analyses suggested that tests of memory
      and attention more analogous to everyday tasks are better predictors of
      functional impairment in MS than both standard clinical tests of memory and
      attention, and memory questionnaires completed by the patient or a significant
      other. Nonetheless, both standard clinical tests and more ecologically valid
      tests significantly predicted functional impairment. Importantly, they were not
      significantly correlated with one another, suggesting that the inclusion of both
      types of tests in evaluating MS patients is warranted.

PMID- 14590549
TI  - Biological versus psychometric intelligence: Halstead's (1947) distinction
      revisited.
AB  - This article reports an investigation into the empirical status of a little
      understood cognitive factor-tactile-kinesthetic ability. To this end, a variety
      of haptic tasks, including three subtests of the Halstead-Reitan
      Neuropsychological Test Battery (HRB), were administered to 108 participants,
      along with established markers commonly employed in contemporary psychometric
      investigations. The results suggest that these subtests of the HRB measure
      cognitive abilities conceptually equivalent to fluid intelligence. Since these
      tests reflect efforts to operationalize Halstead's (1947) concept of "biological
      intelligence," the results reported herein allow evaluation of this concept in
      relation to current models of human intelligence. Previous studies investigating
      the nature of abilities assessed by the HRB have reached contradictory
      conclusions. Present findings clarify the source of these anomalies.

PMID- 14590550
TI  - Validation of a new technique to detect malingering of cognitive symptoms: the b
      Test.
AB  - We administered the b Test, a new measure to identify malingering requiring
      recognition of overlearned information, to 34 suspected malingerers and to 161
      subjects in various clinical groups (moderate to severe head injury, elderly
      depressed, learning disability, schizophrenia, right and left CVA, and elderly
      normals). Comparisons of groups revealed more commission and omission errors in
      the suspected malingerers relative to all groups except the right stroke
      patients. In addition, suspected malingerers took longer to complete the task
      than all groups except right and left stroke patients and normal elderly. A
      cutoff of >2 commission errors produced a sensitivity of 76.5% and specificity
      for all comparison groups combined of 82.6%. Lower sensitivity rates were
      documented for omissions (58.8 using cutoff of >40) and time (57.6% using cutoff
      of >12 minutes), but specificity remained high at 85.1% and 83.9%, respectively.
      Thus, the b Test shows considerable potential as a malingering detection tool.

PMID- 14590551
TI  - Developmental changes in California Card Sorting Test performance.
AB  - The purpose of the present study was to determine 1) if performance on the
      California Card Sorting Test (CCST) follows the same developmental gradient as
      other measures of concept formation and 2) whether the components of concept
      formation tapped by the CCST are developmentally dissociable. Participants were
      68 children and young adults in four age-based groups: 7 to 9 years (n = 13); 10
      to 12 years (n = 16); 17 to 19 (n = 20); and, 20 to 22 years (n = 19). All were
      of average or higher measured intelligence and screened for neurological,
      psychiatric, reading and attentional disorder. The findings of the present study
      suggest that like many other concept formation tasks, CCST performance
      approximates adult levels by age 10. Further, the different components of concept
      formation measured by the CCST are dissociable in the youngest children with the
      development of concept recognition preceding sorting ability.

PMID- 14590552
TI  - Neuropsychological outcome of head injury using a short battery.
AB  - The purpose of this study was to demonstrate that a semi-flexible
      neuropsychological test battery would accurately identify and discriminate head
      trauma severity levels. In addition, it was intended to demonstrate that this
      same battery could discriminate head trauma individuals from individuals with
      other diagnoses. Participants were patients referred for a neuropsychological
      evaluation. All patients were administered a battery of tests taking
      approximately 3 hours. It was found that the semi-flexible battery was able to
      differentiate patients grouped into six different severity levels of loss of
      consciousness (LOC). In addition, the battery was able to differentiate patients
      with diagnoses including mental health diagnosis, CVA, dementia, and head trauma.
      These results support previous findings, but utilized a semi-flexible test
      battery to do so. This shorter battery is beneficial to patient,
      neuropsychologists, and managed care providers alike.

PMID- 14590553
TI  - On the reliability, validity, and cognitive structure of the Thurstone Word
      Fluency Test.
AB  - The Thurstone Word Fluency Test (TWFT) is a widely used neuropsychological
      instrument. However, data regarding its psychometric properties are lacking. The
      results of the present study suggest that the TWFT possesses excellent test
      retest and inter-rater reliability, in addition to good construct validity.
      However, its criterion validity is limited by its lack of specificity and
      sensitivity. The present study also suggests that the TWFT is a complex cognitive
      task, and that successful TWFT performance depends upon a constellation of
      cognitive abilities, including attention/concentration, psychomotor speed, and
      memory. Finally, the relationship between verbal IQ and TWFT letter association
      value was examined. While the TWFT appears to be useful in detecting the presence
      of cerebral dysfunction, it is of less value in localizing such dysfunction. It
      is argued that the TWFT should not be used as a neuropsychological screening
      instrument, but rather, is best used within the context of a thorough
      neuropsychological examination.

PMID- 14590554
TI  - An exploration of the construct validity of the Heaton memory tests.
AB  - The Heaton techniques for assessing memory differ from most other memory measures
      by employing the combination of learning trials, repeated exposure to test
      stimuli, and 4-hour recall measures. The present study was designed to explore
      the relationship between the Heaton Story and Figure memory procedures, the
      California Verbal Learning Test (CVLT), and measures of attention, word fluency,
      and spatial perception. Data from 126 individuals were analyzed. Three separate
      factor analyses were performed that examined measures of attention, learning, and
      recall. Each revealed a three-factor solution accounting for 71, 70, and 72% of
      the variance, respectively. Regression analyses supported the visual components
      of Figure Memory and the verbal components of Story Memory obtained in the factor
      analyses. Overall, the findings supported the independence of the Heaton Memory
      procedures and the role of spatial factors in performance of Figure Memory.
      Additionally, both Figure and Story Memory shared variance with the CVLT,
      supporting the validity of both procedures as memory measures.

PMID- 14590555
TI  - Further investigation of traumatic brain injury versus insufficient effort with
      the California Verbal Learning Test.
AB  - The present study replicates and attempts to extend previous research using the
      California Verbal Learning Test (CVLT) to identify malingerers. Documented
      moderate and severe traumatic brain injury patients (n = 42) were compared with
      clinical malingerers identified by criteria other than the CVLT (n = 21),
      malingering simulators instructed in realistic potential injury sequelae (n =
      25), and normal controls (n = 21). Results of discriminant function analyses for
      high and low base rates are reported, showing similar results. Also, the four
      individual cutoff scores (Recognition Hits, Discriminability, Total Words
      Recalled, Long Delay Cued Recall) from Millis, Putnam, Adams, and Ricker (1995)
      were evaluated with these groups. Similar specificity rates were found with all
      four variables, while sensitivity rates were slightly lower than that of Millis.
      Adjusted cutoffs derived from the new samples resulted in slightly improved
      overall classification rates. Overall, present findings support those of Millis
      et al. (1995) with regard to the use of the CVLT in detection of malingering.
      Exploratory use of Total Intrusions and Recognition Hits Compared to Long Delay
      Free Recall was not promising. Simulators were found to be fairly comparable in
      performance to actual malingerers, affirming their use in malingering research.

PMID- 14590556
TI  - Distinct neurocognitive profiles in multiple sclerosis subtypes.
AB  - An effect size analysis was used to review the neuropsychological literature of
      multiple sclerosis (MS) to determine whether reliable neurocognitive test
      deficits and differences between chronic-progressive and relapse-remitting
      subtypes are apparent. Studies dating back to 1983 were gathered and the
      neuropsychological test results from a total of 1,845 patients with MS, and 1,265
      healthy controls, were synthesized using meta-analytic principles. The results
      indicate that neurocognitive impairment is indeed evident in patients with MS on
      a number of cognitive tasks and test variables. Secondly, distinct patterns of
      neurocognitive deficits are evident in chronic-progressive and relapse-remitting
      subtypes of MS. Finally, relations between neurocognitive impairment and clinical
      and demographic attributes of patients with MS were revealed.

PMID- 14590557
TI  - A comparison of alternative approaches to the scoring of clock drawing.
AB  - Although a number of scoring procedures for clock drawing have emerged in the
      literature, no systematic comparison of the psychometric properties of various
      approaches has yet been conducted on a large sample of persons over 64 years of
      age diagnosed with dementia or deemed cognitively intact. The present study
      examined the reliability and validity of five scoring approaches (Doyon,
      Bouchard, Morin, Bourgeois, & Cote, 1991; Shulman, Shedletsky, & Silver, 1986;
      Tuokko, Hadjistavropoulos, Miller, & Beattie, 1992; Watson, Arfken, & Birge,
      1993; Wolf-Klein, Silverstone, Levy, Brod, & Breuer, 1989) among the 493
      participants of the Canadian Study of Health and Aging who completed clock
      drawing and who had a final diagnosis assigned at the conclusion of a
      comprehensive clinical examination. Inter- and intra-rater reliabilities were
      highest for the Tuokko et al. method. The Tuokko and Shulman scoring procedures
      had the highest sensitivities and relatively low specificities. The Wolf-Klein
      procedure had relatively low sensitivities and high specificities. Estimated
      areas under receiver operating curves were relatively high for all scoring
      methods. However, the area under the curve for the Watson procedure was
      significantly lower than the other procedures. All claims to the utility of clock
      drawing for differentiating between normal persons over 64 years of age and those
      with dementia appear validated.

PMID- 14590558
TI  - Qualitative block design performance in epilepsy patients.
AB  - Broken configuration errors on the WAIS-R Block Design subtest have been
      associated with right hemisphere brain damage. This study examined whether pre
      surgical epilepsy patients with seizure foci restricted to the right hemisphere
      would break configuration more frequently than those with left hemisphere foci.
      Subjects included 38 patients with unilateral right or left hemisphere epilepsy
      of frontal or temporal lobe origin. The left and right hemisphere groups did not
      differ significantly in demographic or disease variables, IQ, or Block Design
      standard scores. Right hemisphere patients made more broken configurations than
      did those with left hemisphere foci. In the right hemisphere group, more broken
      configurations were associated with a lower Block Design Scaled Score and Full
      Scale IQ. These results suggest that the observation of broken configurations in
      the Block Design can assist in corroborating the seizure focus and highlight the
      importance of qualitative Block Design analysis.

PMID- 14590559
TI  - Short forms of the Benton Judgment of Line Orientation Test: development and
      psychometric properties.
AB  - The Benton Judgment of Line Orientation Test (BJLOT) is a widely used
      neuropsychological test measuring visuospatial judgment. The present study
      developed two 15-item short forms using data from 100 neurologic patients. The
      new short forms are equivalent in test construction and retain the stimulus
      properties of the original test. Correlational analyses revealed that each short
      form score related significantly to the original BJLOT (p <.001). The short forms
      were found to be internally consistent, with alpha reliability coefficients
      exceeding .82. Although kappa coefficient analyses found the short forms to lack
      sufficient accuracy in categorizing the cases via the BJLOT diagnostic
      classifications, the short forms were accurate in detecting the presence of
      impairment. These results suggest that the two short forms can be utilized as
      screening instruments for detecting the presence or absence of visuospatial
      impairment.

PMID- 14590560
TI  - Familial Creutzfeldt-Jakob disease: a neuropsychological case study.
AB  - The spectrum of neuropsychological features of familial Creutzfeldt-Jakob disease
      (CJD) have seldom been reported, possibly because of (a) the rarity of this
      hereditary form of prion disease; (b) frequent delays in diagnosis, and; (c) the
      typically rapid demise of the patient, which affords little opportunity for
      comprehensive testing or serial analysis. Here we describe the neurobehavioral
      characteristics of a 48-year-old right-handed male (JD) who presented with
      complaints of poor depth perception, unsteady gait, and unusual sensory
      experiences in his face and neck. JD was followed serially over the final 4
      months of his 5-month illness. Immediately following hospital admission, he
      underwent a neuropsychological evaluation that revealed moderate to severe
      impairment of delayed (30-minute) verbal memory, tactual performance in his right
      hand, and word-finding ability. In contrast, other abilities that are commonly
      classified within the verbal, visuospatial, and memory domains showed minimal or
      no compromise. Parallel studies of electroencephalographic activity revealed
      diffuse slowing and, later, 1-Hz rhythmical discharges over the left hemisphere,
      and mild prominence of the lateral ventricles and cerebral sulci on magnetic
      resonance imaging. Autopsy revealed spongiform changes and reactive astrocytosis,
      and genetic testing demonstrated a codon 200 mutation in the prion protein gene.
      These findings indicate that CJD can result in clinical manifestations compatible
      with multifocal asymmetric cerebral involvement before more diffuse
      neurodegeneration ensues, providing a strong impetus for the study of additional
      cases. This long-term understanding can help to determine whether the multiple
      loci of clinical involvement are specified by genetic or epigenetic factors, or
      both.

PMID- 14590561
TI  - The use of Luria's method for the neurobehavioral assessment of encephalopathy in
      an adolescent: application in a rehabilitation setting.
AB  - Standardized neuropsychological test batteries demonstrate their greatest
      reliability and validity in patients with focal, well-defined neurologic disease.
      In these patients, the test profiles typically highlight focal areas of strengths
      and weaknesses in the brain. However, the clinical utility of standard test
      batteries and their reliance on scaled score differences is limited when
      evaluating patients with severe or diffuse neurobehavioral disorders. In the
      present case study, we applied the qualitative approach of Alexander Luria to the
      neuropsychological evaluation of a severely impaired adolescent, unable to
      complete psychometric tests. Luria's investigative method was able to assist in
      the localization of the brain dysfunction and the neurologic diagnosis of a young
      patient with an unusual neurologic presentation secondary to serious multisystem
      disease. The initial neuropsychological diagnostic impressions were later
      confirmed by diagnostic testing. The test results were also used to provide
      recommendations for ongoing neurorehabilitation of the patient.

PMID- 14590562
TI  - Note on the use of the Postconcussion Syndrome Checklist.
AB  - Symptoms of the Postconcussion Syndrome (PCS) were evaluated in a university
      sample, using the Postconcussion Syndrome Checklist (PCSC). Three hundred twenty
      six participants completed a questionnaire regarding history of head injury,
      cognitive or psychosocial difficulties, and demographic data. Scores on the PCSC
      did not vary by self-report of head injury. Females, however, endorsed more
      frequent, intense, and prolonged symptomatology, regardless of history or
      severity of head injury. Only 5% of the sample endorsed more than 6 symptoms on
      the PCSC, suggesting a potentially useful cutoff for abnormality. The PCSC was
      significantly correlated with the Beck Depression Inventory, suggesting that
      general level of psychological distress is a key factor in evaluating symptoms of
      PCS.

PMID- 14590563
TI  - Differentiation of dementia of the Alzheimer's type from depression with
      cognitive impairment on the basis of a cortical versus subcortical pattern of
      cognitive deficit.
AB  - This study compared 15 "mildly" cognitively impaired participants with Dementia
      of the Alzheimer Type (DAT), 15 depressed cognitively impaired participants
      (DCI), and 15 normal participants. The participants were matched for age, and
      reading ability, and were tested on a series of cognitive instruments selected on
      the basis of their ability to distinguish a cortical versus subcortical pattern
      of deficit. The DAT group demonstrated impaired performances on tests of
      language, praxis and gnosis. Deficits in these areas were absent from DCI group.
      There were differences between all of the groups on the California Verbal
      Learning Test, but after this effect was controlled using an analysis of
      covariance procedure, the differences in tests of gnosis, praxis and language
      function between the DCI and the DAT participants still remained. These findings
      support the clinical usefulness of the cortical-subcortical distinction in
      differentiating DCI from DAT.

PMID- 14590564
TI  - Is SIB or BNP better than MMSE in discriminating the cognitive performance of
      severely impaired elderly patients?
AB  - The sensitivity of the Mini Mental State Evaluation (MMSE) in severely impaired
      patients is reduced by a floor effect and limited score range. The Severe
      Impairment Battery (SIB) and Preliminary Neuropsychological Battery (BNP) may be
      valid alternatives. We studied a group of 37 severely compromised elderly
      inpatients to investigate the usefulness of these two test batteries as
      alternatives to the MMSE. Both proved reliable, but only the SIB had a wider
      distribution of results with respect to the MMSE in the lower score range. The
      BNP, that might be thought easier to perform being a simple verification task,
      could actually not be completed by the most compromised patients. The SIB seems
      better able than the MMSE to provide cognitive profile in the three diagnostic
      categories into which patients were subdivided (Psychogeriatric, Psychorganic,
      Mentally Retarded). We conclude that it may be useful to test patients with the
      SIB when they yield a MMSE score lower than 10-12 points.

PMID- 14590565
TI  - Correlation between intelligence test scores and executive function measures.
AB  - In this study, some executive function measures (Wisconsin Card Sorting Test
      [WCST], verbal fluency, and Trial Making Test [TMT], Form A and Form B) were
      correlated with Wechsler Intelligence Scale for Children-Revised (WISC-R) scores.
      Fifty 13- to 16-year-old normal children were selected. It was found that verbal
      fluency tests correlated about 0.30 with Verbal Intelligence Quotient (IQ) and
      Full Scale IQ. In the WCST only Perseverative Errors negatively correlated with
      Verbal IQ and Full Scale IQ. Two correlations were found to be significant with
      regard to the TMT: TMT Form B Errors negatively correlated with WISC-R Vocabulary
      subtest; and TMT Form A Time negatively correlated with Performance IQ. These
      results support the assumption that traditional intelligence tests are not
      appropriately evaluating executive functions.

PMID- 14590566
TI  - Memory functioning and emotional changes in early phase multiple sclerosis.
AB  - Memory functioning and emotional changes were evaluated in 26 early phase
      multiple sclerosis (MS) patients, as compared with 24 healthy controls. There
      were no significant differences between the groups with respect to age,
      education, verbal intelligence, or general visual information processing
      abilities. The MS group performed significantly below controls on the recognition
      of nonsense visual stimuli. On most verbal memory test indicators, the MS group
      did not perform deficiently, but there emerged a between-group difference at
      trend level on a measure reflecting sensitivity to proactive inhibition. The MS
      patients reported emotional changes and increased levels of psychological
      symptoms in several areas. Memory task performance was not significantly
      correlated with subjective complaints of memory impairment, depressive symptoms,
      or degree of physical disability. However, subjective complaints of memory
      impairment were related to depression.

PMID- 14590567
TI  - Novel learning abilities after traumatic head injury in children.
AB  - The cognitive abilities of 69 children with traumatic head injury (THI) were
      evaluated with the California Verbal Learning Test-Children's Version (CVLT-C;
      Delis, Kramer, Kaplan, & Ober, 1994), the Children's Category Test (CCT; Boll,
      1993), and the Wechsler Intelligence Scale for Children-Third Edition (WISC-III;
      Wechsler, 1991). Compared to children with mild to moderate injuries, children
      with severe THI demonstrated statistically significant impairments on the CVLT-C
      Total T-score as well as the WISC-III Processing Speed index, but findings for
      the CCT were less robust. Longer length of coma and male gender were associated
      with relatively poorer performance on the CVLT-C. Children with severe THI
      demonstrated difficulties with both capacity and speed of information processing,
      which could not be accounted for by attentional or general verbal knowledge
      factors. It is concluded that the combination of the CVLT-C and the WISC-III is
      useful in the evaluation of cognitive sequelae of THI but that findings from the
      CCT must be considered with some caution in this population.

PMID- 14590568
TI  - Neuropsychological sequelae in a series of patients with end-stage cystic
      fibrosis: lung transplant evaluation.
AB  - There has been a relative absence of studies that examine the neuropsychological
      profiles of patients suffering from cystic fibrosis. Data are presented here for
      18 individuals with end-stage cystic fibrosis who were also potential candidates
      for lung transplantation. Neuropsychological test results indicated a diversity
      of memory and executive control deficits, the most frequent of which were
      immediate and delayed free recall and retrieval impairments on a memory measure
      involving noncontextual verbal material. The majority of this sample of patients
      suffering from cystic fibrosis also exhibited clinically significant elevations
      on the Minnesota Multiphasic Personality Inventory-2 and Minnesota Multiphasic
      Personality Inventory-Adolescent (MMPI-2/MMPI-A), which are suggestive of
      heightened levels of psychological distress (e.g., depressive symptomatology) and
      multiple somatic complaints. These findings are discussed in light of factors
      associated with end-stage cystic fibrosis. Implications for clinical practice and
      future research are also provided.

PMID- 14590569
TI  - Neuropsychology, the patient's experience, and the political forces within our
      field.
AB  - This article emphasizes the importance of both scientific and phenomenological
      approaches to the practice of clinical neuropsychology. Paying attention to
      patients experiences while they receive neuropsychological services is stressed
      because this aspect is often neglected in the training of clinical
      neuropsychologists. Finally, the reality of "hostile" forces within the politics
      of neuropsychology is considered briefly. Neuropsychologists need to consider
      three major issues that are important to our field and to the National Academy of
      Neuropsychology. First, neuropsychology is a scientific enterprise that deserves
      continued efforts at scholarship and clinically relevant research. The second
      issue concerns how scientific information is applied to patient care and the need
      for clinical neuropsychologists to understand both personal suffering and
      empirical data. The third issue is more delicate. It concerns the political
      forces in our field and my related personal observations.

PMID- 14590570
TI  - Verbal memory impairments in dyslexia.
AB  - Although verbal memory deficits are frequently reported in reading disabled
      children, the specific mechanisms underlying these impairments have yet to be
      clearly defined. The present study used the California Verbal Learning Test
      Children's Version (CVLT-C) to assess verbal learning in 57 dyslexic children and
      114 controls matched for gender, age, and WISC-R Vocabulary score. Three areas of
      verbal memory were investigated: Recall and recognition, use of learning
      strategies, and interference effects. The dyslexic group learned the list items
      more slowly, recalled fewer words on the last learning trial and the delayed
      trials, and performed less well on the recognition condition. Dyslexics and
      controls displayed similar vulnerability to interference, but group differences
      were evident in serial position effects. Taken together, our data suggest that
      dyslexics have less efficient rehearsal and encoding mechanisms, resulting in
      deficient encoding of new information, but normal retention and retrieval.

PMID- 14590571
TI  - The future of neuropsychology with Hispanic populations in the United States.
AB  - This article discusses neuropsychology within the Spanish-speaking world; it
      reviews its recent history, existing efforts, and future directions. It also
      addresses the practice of neuropsychology with Hispanics in the United States and
      posits that it should take into account the heterogeneity of this population (the
      largest minority group in the country). Hispanic heterogeneity includes, among
      other variables, ethnicity, language, acculturation, age and education. Data from
      current research suggest that these are relevant variables affecting the
      psychometrics of cognition and therefore, the practice of neuropsychology with
      this population. Suggestions for future research are also addressed.

PMID- 14590572
TI  - The influence of culture on cognition.
AB  - This article presents a theoretical and methodological framework that seeks to
      integrate multiple sources of pertinent data that must be taken into account to
      interpret neuropsychological test results of individuals of non-European
      ancestry. It is proposed that cultural factors have a determining influence on an
      individual's behavior regardless of the neurophysiological status of the brain. A
      differentiation is made between the effects of culture/language and socioeconomic
      level on cognitive testing results and suggestions are made to assist in
      discriminating between these variables. Taking as illustration the assessment of
      Latino patients, focus is given to the accurate neuropsychological evaluation of
      individuals with little education, of non-European cultures, and with a primary
      language other than English.

PMID- 14590573
TI  - Neuropsychological test development and normative data on Hispanics.
AB  - The development of culturally relevant psychological assessment tools and
      intervention procedures has not been commensurate with the rate of Hispanic
      population growth in the United States. The development of valid and reliable
      test measures for the assessment of this population must be based on empirical
      investigations. In this article, we present normative data on multiple measures
      from the Benton Laboratory and the Wisconsin Card Sorting Test. Results revealed
      equivalent findings for our Hispanic subjects and the English-speaking samples
      utilized in the original normative studies within the United States. We
      additionally review current trends and specific problems encountered in
      neuropsychological research with Hispanics, and suggest guidelines and directions
      for future research.

PMID- 14590574
TI  - Patterns of American immigration and their influence on the acquisition of
      neuropsychological norms for Hispanics.
AB  - This article examines patterns of legal American immigration (migrations to the
      United States from abroad) and their direct impact on the acquisition of
      neuropsychological (NP) normative data for Hispanics. The nonrandom and selective
      nature of these migrations, and their accompanying demographic attributes, are
      shown to significantly influence the acquisition process. Specifically, the
      direct impact of several potential sources of bias while procuring NP norms is
      explored. Total number of immigrants (absolute immigration), occupational
      allegiance (and possibly education), and intended area of initial residence seem
      to play influential roles as a result of their direct impact on demographic
      characteristics known to have significant effects on neuropsychological
      performance. Possible solutions capable of enhancing the acquisition process are
      also addressed.

PMID- 14590575
TI  - An empirically derived short form of the Boston naming test.
AB  - The Boston Naming Test (BNT) is one of the most commonly used tests of
      confrontation naming. The length of the test, particularly when administered to
      impaired patients, has prompted the derivation of several abbreviated forms.
      Short forms of the BNT have typically been equated in terms of difficulty, but
      not empirically derived for discriminating between normals and anomic patients.
      Furthermore, most reports to date have been limited in sample size and
      generalizability. The present study examined BNT data from a total of 1,044
      subjects, including 719 normals and 325 patients with Alzheimer's disease (AD).
      Scores were calculated for the entire 60-item version as well as for eight
      previously reported short forms. The scores were examined for the effects of age,
      education, and gender, as well as for the ability of each form to discriminate
      between AD patients and normals. There was a significant effect of age,
      education, and gender on all previously published forms, and the short forms
      varied in their ability to discriminate between patients and controls. A stepwise
      discriminant analysis was conducted to empirically derive a new, gender-neutral
      short form with discriminability comparable to the full 60-item test. Norms from
      this sample on the empirically derived short form are reported.

PMID- 14590576
TI  - Determinants of confrontation naming performance.
AB  - Confrontation naming tests are commonly employed in neuropsychological
      assessment. Surprisingly little work has been done, however, to determine how
      various demographic, linguistic, and disease status variables influence patterns
      of performance on these tests. The present study examined data on the Boston
      Naming Test (BNT) from a total of 1,131 subjects, including 719 normals, 325
      patients with Alzheimer's disease, and 87 patients with temporal lobe epilepsy.
      The effects of age, education, gender, and diagnostic group were examined with
      respect to overall scores, the influence of phonemic cuing, and performance on
      individual items. Profiles of scores on individual items were similar across
      diagnostic groups, suggesting that anomia is characterized by quantitative rather
      than qualitative changes in naming performance. Age and education systematically
      influenced scores. There was a significant effect of gender across diagnostic
      groups (males scoring higher than females), which appears to be due to
      performance on specific items. Phonemic cuing effects were similar across groups.
      The results are discussed with respect to the neuropsychological construct of
      confrontation naming and the clinical interpretation of performance on the BNT.

PMID- 14590577
TI  - The Wisconsin Card Sorting Test in stroke rehabilitation: factor structure and
      relationship to outcome.
AB  - The present study attempted to replicate the findings of previous factor analytic
      studies of the Wisconsin Card Sorting Test (WCST) in a homogeneous sample of
      patients suffering recent cerebrovascular accidents and being treated in a
      comprehensive inpatient physical rehabilitation program. In addition this study
      examined the relationship of the WCST to standard measures of functional ability
      used in many rehabilitation programs. The results confirmed the previously
      reported three-factor structure and replicated past findings concerning the
      test's construct validity. A small but significant relationship was noted between
      the WCST and functional status, though the WCST did not make a unique
      contribution to the prediction of functional status at discharge. This study
      highlights the similarities and differences in WCST factor structure in a stroke
      sample compared to a more general neurological sample and raises questions about
      the utility of the WCST in stroke rehabilitation.

PMID- 14590578
TI  - Comment: Warning malingerers produces more sophisticated malingering.
AB  - Warning persons that attempts to malinger on neuropsychological testing will be
      detected is not an effective way of reducing malingering behavior. Rather, the
      literature on coaching consistently shows that malingerers who are warned of the
      presence of symptom validity assessment techniques are able to feign deficits in
      a less exaggerated and more believable fashion and therefore elude detection.
      Warning persons about the presence of these techniques reduces the validity and
      scientific quality of forensic evaluations. Rather than warning persons that they
      will be caught if they try to malinger, we recommend that persons be told to do
      their best and that forensic examiners encourage maximum effort, consistent with
      accepted testing practices and test manual instructions.

PMID- 14590579
TI  - Neuropsychological test performances of young depressed outpatient women. An
      examination of executive functions.
AB  - Thirty young, unmedicated, outpatient, depressed women were compared to an equal
      number of matching controls on a series of neuropsychological tests purported to
      be sensitive to the executive functions. Specifically, the measures included the
      Design Fluency Test, Hand Dynamometer tasks of grip strength, perseveration, and
      fatigue, the FAS Verbal Fluency Test, the Stroop Color and Word Test, and the
      Trail Making Test (Parts A and B). Despite past research which has indicated
      anterior hemispheric asymmetries and impaired neurocognitive performances in
      depressives, this research failed to identify any reliable differences between
      depressed and nondepressed women on any of the neuropsychological measures. These
      results argue against the frequently held stereotype that depressed individuals
      typically display impaired performances on neurocognitive tasks. Furthermore,
      since the profile of the depressed sample appeared to differ significantly from
      past studies, a discussion is provided as to how the characteristics of this
      group may have impacted the results. Implications of these findings for clinical
      practice and future research are also provided.

PMID- 14590580
TI  - Subjective cognitive complaints, affective distress, and objective cognitive
      performance in Persian Gulf War veterans.
AB  - We examined subjective cognitive complaints, affective distress, and cognitive
      performance in Persian Gulf veterans who reported illness and cognitive
      complaints. We predicted a stronger relationship between subjective cognitive
      complaints and affective distress than between subjective cognitive complaints
      and objective cognitive performance. This prediction was confirmed in a sample of
      100 veterans. The results suggest that cognitive impairment should not be
      diagnosed in this population without objective confirmation with cognitive
      testing.

PMID- 14590581
TI  - Astereopsis caused by traumatic brain injury.
AB  - Impaired depth perception (astereopsis) has been observed in a variety of
      cerebral pathologies affecting the posterior parietal lobe. In the current study
      of 93 consecutive head trauma admissions, 24% had complete astereopsis and 41%
      performed more than 2 SDs below the orthopedic control group mean. Degree of
      impairment was related to Glascow Coma Scale score, length of posttraumatic
      amnesia, reduced visuospatial and memory abilities, and the presence of
      intracranial pathology of the parietal lobes. Impairment was also related to
      trauma severity in patients without any visualized intracranial pathology,
      presumably due to diffuse axonal shearing. Clinically meaningful impairment was
      observed in 25% of this group; 10% had complete astereopsis. Stereoacuity
      screening requires 1 to 2 minutes. Undetected astereopsis may increase risk for
      subsequent motor vehicle accidents or falls.

PMID- 14590582
TI  - Performance of 225 Dutch school children on Rey's Auditory Verbal Learning Test
      (AVLT): parallel test-retest reliabilities with an interval of 3 months and
      normative data.
AB  - Performance on Dutch adaptations of Rey's AVLT was examined in a sample of 225 6-
      to 12-year-old Dutch school children, selected to be representative of the
      general population. With an interval of 3 months, they were tested twice, using
      two out of three test forms which proved to be parallel. No test-retest practice
      effects were apparent. Age had a considerable impact on test performance.
      Measured imperfectly, socioeconomic background and intellectual level had some
      additional influence, as did the examiner who administered the tests. Boys made
      more errors than girls. Normative data corresponded well with those collected in
      a smaller Australian sample, suggesting usefulness outside The Netherlands. With
      a parallel test-retest reliability of.70, which was reduced to.59 when the
      influence of age was taken into account, the most reliable AVLT measure was the
      total number of words correctly recalled over the five learning trials. On the
      basis of reliability data, implications for the clinical use of the AVLT are
      discussed.

PMID- 14590583
TI  - Prevalence and correlates of category versus letter fluency discrepancies in
      Alzheimer's disease.
AB  - Alzheimer's disease (AD) patients typically exhibit greater category than letter
      fluency impairment, but the prevalence of this discrepancy has not been studied
      in a large group of patients. In the present study of 217 AD patients, we found
      that 145 subjects (66.8 %) demonstrated the expected pattern of better letter
      fluency (FAS test, i.e, generating as many words as possible in 1 minute
      beginning with "F", "A," and "S") than category fluency (animal generation).
      However, an unexpectedly large group of patients exhibited the opposite pattern
      of category fluency equal to or better than letter fluency (n = 72, 33.2%).
      Paired t-tests between groups revealed no significant differences on demographic
      variables such as age, gender, education level, or duration of illness. However,
      the smaller group exhibiting the unexpected fluency pattern exhibited
      significantly higher Mini-Mental State Examination (MMSE; Folstein, Folstein, &
      McHugh, 1975) scores compared to the larger group. Comparisons were made between
      group performance on other neuropsychological tasks, using MMSE performance as a
      covariate, but no significant differences were found. Therefore, the present
      results do not offer strong support for the neuropsychological (and possibly
      neuroanatomical) distinctiveness of the two fluency subgroups.

PMID- 14590584
TI  - Expanded scoring criteria for the design fluency test: reliability and validity
      in neuropsychological and college samples.
AB  - In spite of sensitivity to right frontal lobe dysfunction, the Design Fluency
      Test (DFT) has been limited by one global score with little psychometric data.
      This study developed an expanded scoring system with standardized instructions
      for multiple dimensions of design performance and provided reliability and
      validity data in a college (n = 64) and diverse neuropsychological sample (n =
      165). The scoring system allowed reliable scoring of number of novel designs,
      complexity of designs, variations in designs, and concrete, frankly
      perseverative, and scribbled responses. Performances for a college sample were
      relatively stable at 1-month retest, but showed practice effects for number of
      novel designs and complexity. Two principal components showed modest, expected
      relationships to other neuropsychological measures in the clinical sample.
      Clinical subjects with a history of closed-head injury or dementing disorder
      showed impaired DFT performances, with complexity the most sensitive indicator of
      impairment.

PMID- 14590585
TI  - Verbal fluency in children: developmental issues and differential validity in
      distinguishing children with attention-deficit hyperactivity disorder and two
      subtypes of dyslexia.
AB  - Previous research studies have shown that in adults, verbal fluency is impaired
      after lesion to the frontal lobes and left temporal lobe. More recently, there
      have been a few studies reported which indicated that in children, like adults,
      left hemisphere and frontal lesions result in pronounced effects on verbal
      fluency. The present study examined developmental differences in verbal fluency
      within a sample of 130 normal children, aged 6 to 12 years. Additionally, the
      same verbal fluency test was administered to two subgroups of children with
      developmental dyslexia and a group of children with attention
      deficit/hyperactivity disorder (ADHD). Analysis of variance (ANOVA) revealed
      significant between-group differences by age in the normal children. Further,
      ANOVA demonstrated that the verbal fluency measure was clinically useful in
      differentiating the Language Disorder/Dysphonetic Dyslexic subgroup from the
      Visual-Spatial/Dyseidetic Dyslexic subgroup and the ADHD group, with the latter
      two groups performing within the average range.

PMID- 14590586
TI  - Normative corrections for the Halstead Reitan Neuropsychological Battery.
AB  - This article investigates the adequacy of the Heaton-Grant-Matthews norms in
      correcting age and education effects in the Halstead Reitan Neuropsychological
      Battery. Two hundred and ninety neurological and 346 psychiatric patients were
      administered the Halstead Reitan Neuropsychological Battery. Raw scores were
      converted to standard scores using the Heaton-Grant-Matthews norms. Ten percent
      of the variance in standard score profiles could be predicted by patient age and
      education. The primary effect of age was to decrease the overall level of the
      profile; the primary effect of education was to increase relative scores on the
      Aphasia test. When these standard scores were converted to age- and education
      corrected T-scores, less than 1% of the variance could be predicted by age and
      education. When individual tests were examined, the Heaton-Grant-Matthews norms
      failed to correct 2% of the variance in the Speech Sounds test. Discussion
      focuses on the usefulness of the Heaton-Grant-Matthews norms in interpreting
      performance on the Halstead Reitan Neuropsychological Battery.

PMID- 14590587
TI  - Cognitive and emotional sequelae of cerebellar infarct: a case report.
AB  - The cerebellum has long been the subject of scientific investigation, but its
      role in nonmotor functions has only recently begun to receive serious
      consideration. Despite the growing literature linking the cerebellum to
      nonmotor/cognitive functions in humans, some controversy remains concerning the
      cerebellum's role in these processes. We present a patient who developed both
      specific language processing and verbal memory deficits and emotional changes in
      the context of normal intelligence following a bilateral cerebellar ischemic
      stroke. Despite having multiple localized cerebellar lesions, this patient had no
      significant motor problems, nor was there radiological evidence of focal
      forebrain lesions to which the cognitive and emotional effects might be
      attributed. The role of the cerebellum in cognition and the relevance of
      cerebellum-associated cognitive/emotional dysfunction to the practicing clinician
      are discussed.

PMID- 14590588
TI  - Comparing methods for estimating premorbid intellectual functioning.
AB  - Efforts to determine premorbid intellectual functioning for a patient prior to
      their current evaluation has been attempted using demographic information,
      current performance data, or a combination of both. Five of these premorbid
      intellectual prediction methods were assessed in a sample of 104 neurological
      patients referred for neuropsychological evaluation and a matched control sample.
      Predicted Full-Scale Intelligence Quotient (FSIQ) scores of patients did not
      differ from the true FSIQ scores of the matched controls. Logistic regression
      analyses found no difference in classification accuracy among the prediction
      methods. The findings of this study found combined demographic and performance
      methods developed by Vanderploeg and Schinka (1995), Vanderploeg, Schinka, and
      Axelrod (1996), Krull, Scott, and Sherer (1995) and Williamson, Krull, and Scott
      (1996) to be accurate estimates of premorbid functioning. This study found
      estimates of premorbid functioning based on demographic data alone (Barona,
      Reynolds, & Chastain, 1984) not to differ from the other methods, which is at
      odds with prior studies. Prospective studies employing all of these methods are
      recommended to clarify the utility of demographically based estimates.

PMID- 14590589
TI  - The neural basis of naming impairments in Alzheimer's disease revealed through
      positron emission tomography.
AB  - The naming impairments in Alzheimer's disease (AD) have been attributed to a
      variety of cognitive processing deficits, including impairments in semantic
      memory, visual perception, and lexical access. To further understand the
      underlying biological basis of the naming failures in AD, the present
      investigation examined the relationship of various classes of naming errors to
      regional brain measures of cerebral glucose metabolism as measured with 18 F
      Fluoro-2-deoxyglucose (FDG) and positron emission tomography (PET). Errors
      committed on a visual naming test were categorized according to a cognitive
      processing schema and then examined in relationship to metabolism within specific
      brain regions. The results revealed an association of semantic errors with
      glucose metabolism in the frontal and temporal regions. Language access errors,
      such as circumlocutions, and word blocking nonresponses were associated with
      decreased metabolism in areas within the left hemisphere. Visuoperceptive errors
      were related to right inferior parietal metabolic function. The findings suggest
      that specific brain areas mediate the perceptual, semantic, and lexical
      processing demands of visual naming and that visual naming problems in dementia
      are related to dysfunction in specific neural circuits.

PMID- 14590590
TI  - Visuoconstructional drawing ability in the differential diagnosis of neurologic
      compromise versus depression.
AB  - Neuropsychologists are often called upon to assist in making differential
      diagnoses between neurologic compromise and depression. However, the literature
      has been inconsistent about the impact of depression on neurocognitive
      functioning. This makes interpretation of neuropsychological test data among
      depressed individuals difficult. In a retrospective cross-sectional study of 200
      patients, the relationship between depression (Beck Depression Inventory or
      Geriatric Depression Scale) and visuoconstructional drawing ability/praxis (Rey
      Osterrieth Copy [RO]) was evaluated. Age and education both correlated
      significantly with RO performance (p <.001 and.005, respectively). There were no
      significant relationships found between copy performance and depression, even
      when controlling for the significant effects of age and education. A prospective
      longitudinal study of 20 psychiatric inpatients with depression tested on
      admission and again at discharge matched with 20 nondepressed normal controls
      yielded similar results in that the two groups did not differ in their initial RO
      performance. Moreover, an improvement in depression as measured by a decrease in
      Beck Depression Inventory scores did not coincide with any improvement in RO
      scores. By comparison, a matched positive control group of 20 neurologically
      compromised patients was significantly worse than both the normal control and the
      depressed groups on the RO (p <.05). These data suggest that poor performance on
      the RO should not be interpreted simply as a consequence of depression. Age and
      education, though, should be considered when interpreting the RO.

PMID- 14590591
TI  - Neuropsychological performance of adults evidencing Attention-Deficit
      Hyperactivity Disorder.
AB  - Attention-Deficit Hyperactivity Disorder (ADHD) is no longer believed to be a
      time-limited syndrome manifested in and restricted to childhood and adolescence.
      Many of the characteristics associated with the disorder continue in variable
      form into adulthood. This investigation focused on two measures sensitive to
      attention, cognitive flexibility, and visual and auditory distraction, to
      determine if individuals diagnosed with ADHD would perform poorly in comparison
      with normal control subjects. Forty-two subjects, 27 ADHD adults and 15 control
      subjects, were administered the Goldman-Fristoe-Woodcock Test of Auditory
      Discrimination (TOAD), and the Stroop Color and Word Test. The findings indicated
      that the TOAD Noise subtest significantly discriminated the subjects, resulting
      in an overall correct classification rate of 80.95%.

PMID- 14590592
TI  - Neuropsychological functioning in migraine headache, nonheadache chronic pain,
      and mild traumatic brain injury patients.
AB  - There are conflicting reports in the literature concerning the neuropsychological
      functioning of migraine headache patients. The finding in some studies that
      migraineurs performed more poorly than healthy controls led to the hypothesis
      that chronic migraine may result in subtle but persistent cerebral dysfunction.
      Reports describing acute and between-headache neurophysiological disturbances in
      migraineurs lent support to this hypothesis. To elucidate the cognitive status of
      these patients, we administered a brief neuropsychological battery to 60
      individuals with migraine headache (HA), nonheadache chronic pain (PAIN), or mild
      traumatic brain injury (MTBI). The PAIN group was included to test the hypothesis
      that cognitive difficulty in migraineurs might result from the discomfort,
      depression, medications, etc. often associated with chronic pain, rather than
      from brain dysfunction. The MTBI patients were considered a useful comparison for
      the migraineurs because their level of impairment was also expected to be mild,
      at worst. A MANOVA, with three cognitive index scores as the dependent variables,
      revealed that the three groups differed significantly. Follow-up contrasts
      demonstrated that the MTBI group was significantly more impaired on the memory
      index compared to the HA and PAIN groups, which did not differ from each other.
      The use of two different normative-based cutoffs to identify individuals who were
      impaired on the test battery revealed that the frequency of impairment within the
      two groups of pain patients, but not the MTBI patients, was within normal limits.
      Thus, the results did not support a link between migraine headache and cognitive
      impairment.

PMID- 14590593
TI  - Serial malingering on verbal and nonverbal fluency and memory measures: an analog
      investigation.
AB  - Analysis of response consistency on neuropsychological test performance, both
      within and across testing sessions, can be an important method of detecting
      malingering. Little systematic research, however, has examined how suspected
      malingerers perform across repeat evaluations, a common forensic occurrence. To
      address this issue, we examined performance across a 3-week interval in an
      analogue malingering design on the California Verbal Learning Test (CVLT), the
      Rey Complex Figure, the Controlled Oral Word Association Test, and the Ruff
      Figural Fluency Test. Malingering simulators (n = 21) performed more poorly on
      all measures than the controls (n = 21) and demonstrated practice effects on the
      nonverbal, but not the verbal, tests. Controls demonstrated practice effects on
      all measures across time. Contrary to hypotheses, malingering simulators
      demonstrated high and similar levels of between and within time consistency as
      controls when assessed via a series of correlations. Despite this consistency,
      when qualitative performance patterns were assessed on the CVLT, simulators were
      less likely to consistently recall the same word across successive learning
      trials. The following issues are discussed: (a) the differential pattern of
      practice effects on verbal and nonverbal tasks, (b) qualitative and quantitative
      differences in assessment of consistency, and (c) how future research should
      study consistency/inconsistency.

PMID- 14590594
TI  - A comparison of phonemic, semantic, and alternating word fluency in Parkinson's
      disease.
AB  - Word fluency in 45 medicated non-demented Parkinson's disease (PD) patients and
      45 normal control subjects was studied with a Phonemic Word Fluency (PWF) task
      using the letters F, A, and S, a Semantic Word Fluency (SWF) task using the
      categories animals, boys' names, and states, and an Alternating Word Fluency
      (AWF) task requiring the person to alternate between colors and occupations,
      animals and states, and words beginning with C and P. The number of words
      generated did not differ for trials with F, A, S, or states, but PD patients
      generated significantly fewer animal names and boys' names. PD patients also
      generated significantly fewer words on each of the three AWF trials. The PD
      patients scored 21% lower than the normal control group on the total AWF score,
      but only 10% lower for the PWF and SWF scores. The greater impairment on the AWF
      task which requires the use of internal attentional control to rapidly shift
      mental set can be considered a type of executive functioning deficit. This is
      consistent with the growing literature suggesting frontal systems dysfunction in
      PD and with the view that dopaminergic treatment only incompletely restores
      functioning in the frontostriatal system.

PMID- 14590595
TI  - WMS-R and MAS correlations in a neuropsychological population.
AB  - The present study was an attempt to examine the relationship between the Wechsler
      Memory Scale-Revised (WMS-R; Wechsler, 1987) and the Memory Assessment Scale
      (MAS; Williams, 1991). The sample consisted of 51 patients referred for
      neuropsychological examination. Average age was 55.29 (SD = 20.94). Average
      education was 11.94 years (SD = 3.18). Average Full Scale IQ was 94.75 (SD =
      15.44). The results showed that no MAS index correlated higher than.60 with any
      of the WMS-R indices. There was minimal specific prediction between instruments
      across each memory domain. Agreement between the tests clinically was low as
      well. Corrections for such factors as age, education, intelligence or diagnosis
      lowered the relationships between the tests although not significantly.
      Corrections to the correlations for the inherent reliability of each test
      increased correlations between the tests but still resulted in a maximum common
      variance of 56% (for the visual measures) down to 40% (for General Memory). These
      results are consistent with the argument that "general memory" is not as useful a
      construct as that of "general intelligence" and that these tests of general
      memory measure different underlying constructs. This has important impact on how
      we conceive and report memory test results.

PMID- 14590596
TI  - The subjective experience of PASAT testing. Does the PASAT induce negative mood?
AB  - The present study investigated the relationship between mood and attentional
      testing in 80 college students. Participants were randomly assigned to a sad,
      anxious, or positive mood induction procedure, or to a neutral procedure.
      Following mood induction, sad and anxious groups reported significantly more
      negative affect than the positive and neutral groups. Following completion of the
      Paced Auditory Serial Addition Task (PASAT), no group differences were found. Sad
      and anxious groups retained their elevated negative mood states, whereas positive
      and neutral mood groups showed significant increases in negative mood states.
      These results are consistent with clinical reports that the PASAT is a stressful
      test. PASAT performance was essentially similar across groups, with the only
      significant difference found between the sad and control conditions at the 1.2
      sec rate of presentation. Results raise the question to what extent participants'
      subjective experience of the PASAT may interfere with their performance on the
      task.

PMID- 14590597
TI  - Performance scales for the Luria-Nebraska Neuropsychological Battery-Form I.
AB  - Regression equations were developed to adjust raw scores on Luria-Nebraska
      Neuropsychological Battery-Form I (LNNB-I) clinical scales for the effects of age
      and education. Corrected raw scores were then used to develop performance scales
      for the LNNB-I on which normal individuals anchored the low end of the scales and
      increasingly impaired patients occupied higher intervals. The resulting scales
      represent equal intervals of age- and education-corrected test impairment for
      each LNNB-I clinical scale and should facilitate interpretation of LNNB-I test
      performances.

PMID- 14590598
TI  - Age, gender, and education may have little influence on error patterns in the
      assessment of set-shifting and rule induction among normal elderly.
AB  - Error patterns have been found to be sensitive to cognitive status, but the
      relationship between aging and error patterns remains unclear, and may differ as
      a function of gender, education, and whether a task is verbal or nonverbal. The
      present study examined the error patterns of normal elderly individuals on a
      verbal measure of set-shifting and rule induction to determine whether
      demographic variables, that is, age, gender, and education, influenced test
      performance. The sample of 109 individuals, 38 males and 71 females, ranging in
      age from 54 to 89 years with 6 to 19 years of education, was assessed on the
      Classification subtest of the Test of Verbal Conceptualization and Fluency, a
      verbal measure of set-shifting and rule induction. Subjects' protocols were
      scored for perseverative, nonperseverative, and random errors, tabulated, and
      analyzed. Multivariate analysis of covariance with education as the covariate as
      well as other statistical tests revealed nonsignificant relationships between
      error scores and age, gender, and education. Years of education, however, showed
      a significant correlation with a reduction in random responses. Results are
      interpreted based on Horn's (1978) fluid-crystallized explanations of changes in
      intelligence with advancing age.

PMID- 14590599
TI  - Reading disability subtypes and the test of memory and learning.
AB  - For Study 1, 24 readers with dysphonetic dyslexia and 21 with dyseidetic
      dyslexia, classified by Boder criteria, were compared to 90 control group
      participants (45 matched for age and 45 for reading level) on the Composite
      Memory Index (CMI) score from the Test of Memory and Learning (TOMAL). CMI scores
      were significantly lower for children with dyslexia (p <.0001). Plotting average
      subtest score profiles for all reader groups revealed auditory sequential memory
      impairments for both types of readers with dyslexia, and multiple strengths for
      good readers. Dysphonetic and dyseidetic dyslexia profiles were nearly identical.
      For Study 2, average linkage cluster analysis was performed using principal
      components derived from subtests of the TOMAL. Homogeneous clusters of normal
      readers and children with reading disabilities emerged. Results indicated that
      qualitatively distinct subtypes of readers with dyslexia exist.

PMID- 14590600
TI  - Normative data stratified by age and education for two measures of verbal
      fluency: FAS and animal naming.
AB  - Normative data stratified by three levels of age (16-59, 60-79, and 80-95 years)
      and three levels of education (0-8, 9-12, and 13-21 years) are presented for
      phonemic verbal fluency (FAS) and categorical verbal fluency (Animal Naming). The
      normative sample, aged 16 to 95 years, consisted of 1,300 cognitively intact
      individuals who resided in the community. Years of education ranged from 0 to 21.
      The total number of words in 1 minute for each of the letters F, A, and S was
      correlated r =.52 with the number of animal names generated in 1 minute.
      Regression analyses showed that FAS was more sensitive to the effects of
      education (18.6% of the variance) than age (11.0% of the variance). The opposite
      relationship occurred for Animal Naming, where age accounted for 23.4% of the
      variance and education accounted only for 13.6%. Gender accounted for less than
      1% of variance for FAS and Animal Naming. The clinical utility of these norms is
      discussed.

PMID- 14590601
TI  - Covert orienting of visual spatial attention in attention deficit hyperactivity
      disorder: does comorbidity make a difference?
AB  - Attentional performance in children with attention deficit hyperactivity disorder
      (ADHD) with and without comorbid disorders was examined using the Covert
      Orienting of Visuospatial Attention Task (COVAT) and the Continuous Performance
      Task (CPT). The relationship between these two tasks was also examined. The
      results showed no overall differences on the attention tasks between children
      with ADHD alone and those with ADHD plus other disorders. Compared to non-ADHD
      control children, children with ADHD showed a deficit in the disengage operation
      of covert visuospatial attention, suggesting a difficulty in the endogenous mode
      of orienting. The ADHD children also showed a general performance deficit on the
      CPT. Although there was a general slowing on both attention tasks in the ADHD
      group, there was no relationship between invalid cue effect sizes on the COVAT
      and the CPT measures. These results indicate that these two attention tasks may
      be tapping both similar and independent underlying cognitive processes in ADHD.

PMID- 14590602
TI  - The two faces of mild head injury.
AB  - The research literature indicates that the great majority of persons who sustain
      any initial neuropsychological impairment from a mild head injury recover in 1 to
      3 months. Nevertheless, clinicians report that some persons with a mild head
      injury demonstrate signs and report symptoms suggesting that they have sustained
      permanent brain damage. Although this latter group contains the participants of
      principal clinical interest, our literature review did not identify any research
      that provided a comprehensive description of the neuropsychological
      characteristics of this important subgroup of mild head-injured persons. The
      present investigation compared four groups: (1) controls, (2) persons with
      definite traumatic brain tissue damage, (3) persons with mild head injuries
      routinely accessed into a research study, and (4) persons with mild head injuries
      who had persisting clinical signs and symptoms. The same comprehensive
      neuropsychological test battery was used to evaluate all four groups. All pairs
      of groups differed significantly in neuropsychological status, with Group 3
      showing only mild impairment (approaching the level of the controls) and Group 4
      showing significant impairment (approaching the level of the group with definite
      brain tissue damage). The results emphasize the need for a comprehensive
      neuropsychological examination of persons with mild head injuries who have
      persisting clinical problems.

PMID- 14590603
TI  - Twenty questions task and frontal lobe dysfunction.
AB  - Performance on the Twenty Questions task has been assumed to be deficient in
      those with frontal lobe damage, although few studies have specifically examined
      this. In the present study, 88 participants with frontal lobe epileptic
      dysfunction were assessed on this task, as were 57 participants with temporal
      lobe epileptic disturbance and 28 participants with no evidence of any
      neurological damage. Results indicated that those with either left or bifrontal
      lobe damage were more impaired on several indexes of test performance. Analysis
      also revealed that participants with orbitofrontal damage were impaired on the
      measure of "first guess" as compared to groups with damage to other regions of
      the prefrontal cortex (p <.05). Overall, the results support the utility of the
      Twenty Questions task in assessing frontal lobe damage and may suggest that
      qualitatively different deficits may be recorded depending on the region of
      frontal lobe dysfunction.

PMID- 14590604
TI  - Neuropsychological correlates of methylphenidate treatment in adult ADHD with and
      without depression.
AB  - The purpose of this study was to characterize the neuropsychological profiles of
      adult patients with attention deficit hyperactivity disorder (ADHD) alone and
      ADHD with active comorbid depression, and to evaluate changes in the
      neuropsychological profile in these two groups following a trial of
      methylphenidate. Forty patients with ADHD were classified into two groups based
      on their affective status resulting in a group of 21 patients with ADHD alone and
      19 patients with ADHD and active comorbid symptoms of depression (ADHD-D). All
      subjects received a comprehensive neuropsychological evaluation including
      measures of cognitive, motor and affective functioning before and after
      treatment. Fifteen normal controls were also assessed at a yoked time interval.
      At baseline, both patient groups showed impairment in verbal memory, motor and
      processing speed, visual scanning, and auditory and visual distractibility.
      Following treatment, both patient groups showed improvement across all
      neuropsychological measures while controls remained relatively stable over time.
      Improvement in neuropsychological test performance was not related to gender,
      affective status or referral source. Patients with active comorbid symptoms of
      depression show a similar neuropsychological profile and appear equally likely to
      benefit from methylphenidate intervention as patients with ADHD alone.

PMID- 14590605
TI  - Continuing decline of memory skills with significant recovery of intellectual
      function following severe carbon monoxide exposure: clinical, psychometric, and
      neuroimaging findings.
AB  - Extensive clinical, psychometric, and neuroimaging data are presented and
      interpreted with regard to a 35-year-old, White male college graduate who was
      exposed to severe carbon monoxide (CO) poisoning. The patient was comatose for 21
      days following the exposure. Several other people, who were in the same room as
      the patient, died due to the toxic effects of the CO. The patient was employed
      premorbidly as a systems level lead computer programmer. The patient received
      medical and neuropsychological follow-up for 3 years post-CO exposure.
      Neuropsychological evaluations revealed a gradual, but incomplete recovery of
      general intellectual function. The patient continued to exhibit severe memory
      deficits with some evidence for small additional memory decline over time.
      Characteristic and permanent vestibular and gait disturbances were also noted,
      along with a variety of neuropsychological deficits that improved over time with
      the exception of memory function. The patient also experienced significant
      affective and personality changes. Neuroimaging studies reveal a generalized
      cortical atrophy as shown by significantly enlarged ventricles and a ventricle-to
      brain ratio that exceeded 4 standard deviations above the norm. The observed
      atrophic changes are consistent with CO-induced anoxic type injury, which was
      also accompanied by bilateral lesions of the globus pallidus, caudate, and
      hippocampus. Despite obtaining average levels of general intellectual functioning
      over time, significant memory impairments, depression, and personality
      disturbances severely impaired the patients' vocational recovery and ability to
      return to work.

PMID- 14590606
TI  - Relationship between stress, coping, and postconcussion symptoms in a healthy
      adult population.
AB  - Study 1 examined the association between intensity of postconcussive symptoms
      (PCS), impact of daily stress, and level of perceived stress over the past month
      in a group of healthy young adults. There was a significant relationship between
      intensity of PCS and impact of daily stress, as well as level of perceived stress
      over the past month, independent of the frequency of stressful events
      experienced. Study 2 assessed the stability of the relationship between PCS and
      stress. Subjects rated intensity of PCS, impact of daily stress, and level of
      perceived stress on two separate occasions approximately 1 month apart. The
      Perceived Stress Scale demonstrated high test-retest reliability. Significant
      relationships were again found between intensity of PCS and level of perceived
      stress at both time points, independent of the frequency of stressful events.
      These results suggest that persistent symptoms in some individuals with
      postconcussive syndrome may be due, at least in part, to individual differences
      in the perceived stress of incurring a mild traumatic brain injury.

PMID- 14590607
TI  - Incidence of the Fuld WAIS-R profile in traumatic brain injury and Parkinson's
      disease.
AB  - The frequency of occurrence of the Fuld Profile for cholinergic deficiency was
      investigated in two clinical populations: inpatients who had suffered traumatic
      brain injury and outpatients who carried a diagnosis of Parkinson's disease. The
      observed incidence of positive Fuld profiles was not significantly different in
      the two groups, 14% in the traumatic brain injury group and 24% in the
      Parkinson's disease group. These findings are consistent with recent reviews of
      the sensitivity and specificity of the Fuld profile in various clinical and
      nonclinical populations. The generally low sensitivity of the Fuld profile does
      not support its usefulness in the differential diagnosis of dementia. However, it
      may serve as an indicator of cholinergic deficiency, which could be used to
      select patients who would be likely to respond to cholinomimetic therapies.

PMID- 14590608
TI  - Motivation for traumatic brain injury rehabilitation questionnaire (MOT-Q):
      reliability, factor analysis, and relationship to MMPI-2 variables.
AB  - A Likert scale questionnaire was developed to assess motivation for postacute
      rehabilitation by traumatic brain injury patients. Items were designed to reflect
      head-injured individuals' statements about their attitudes toward head injury
      rehabilitation. Factors such as denial of illness, anger, compliance with
      treatment, and medical information seeking behavior were used to assess
      unfavorable and favorable components of motivation. Reliability was assessed
      using Cronbach's Alpha, which was found to be 0.91 for the total scale. Four
      factor analysis derived subscales were identified: Lack of Denial, Interest in
      Rehabilitation, Lack of Anger, and Reliance on Professional Help. Correlation and
      multiple regression analyses demonstrated moderate relationships between MOT-Q
      and several MMPI-2 variables largely related to indicators of somatic distress,
      depression and capacity for self-sufficiency. Lack of Denial subscale showed the
      strongest relationship to MMPI-2 of all MOT-Q variables, while Interest in
      Rehabilitation showed the best correlation to the MOT-Q total.

PMID- 14590609
TI  - Letter and semantic fluency in Alzheimer's, Huntington's, and Parkinson's
      dementias.
AB  - A pattern of semantic fluency worse than letter fluency has been presented as
      evidence of impaired semantic networks in "cortical" dementias (e.g., Alzheimer's
      disease), distinguishing them from "subcortical" dementias (e.g., Parkinson's
      disease, Huntington's disease). However, there have been few systematic studies
      of this propositions. The present study compared Alzheimer's, Parkinson's, and
      Huntington's disease subjects with mild dementia to each other and to matched
      normal controls on letter and semantic fluency tasks. Results revealed parallel
      semantic/letter fluency patterns for all groups, suggesting that there is no
      unique pattern of semantic/letter fluency deficits for "cortical" or
      "subcortical" dementias. Qualitative errors (repetitions, intrusions) were also
      evaluated. Huntington's subjects had significantly more repetition errors than
      all other groups, and Alzheimer's subjects had significantly more repetition
      errors than Parkinson's subjects and normal controls. There were no differences
      in number of intrusion errors. Findings suggest that semantic fluency deficits
      are not unique to Alzheimer's dementia and may not help to differentiate between
      different etiologies of dementia.

PMID- 14590610
TI  - Amnestic disturbance and posttraumatic stress disorder in the aftermath of a
      chemical release.
AB  - Neuropsychological assessments were performed on 70 patients referred after a
      Catacarb chemical release in a Northern California town. After appropriate
      exclusions, the 59 patients used in the final analysis were mostly White (66%),
      with 56% having some college level education. They were administered the:
      Wechsler Adult Intelligence Scale-Revised (WAIS-R), Memory Assessment Scale
      (MAS), Trails A and B, Stroop, Controlled Oral Word Association Test (COWAT),
      Fingertapping Test, Purdue Pegboard, Dynamometer, Rey 15-Item Test, Minnesota
      Multiphasic Personality Inventory-2 (MMPI-2), Brief Symptom Inventory (BSI), Beck
      Depression Index (BDI), Profile of Mood States (POMS), and Impact of Events Scale
      (IES) scales in addition to a health questionnaire and symptom checklist. Results
      indicate impaired scores on mnestic function and information processing when
      compared to Heaton's (1992) normative data, and the MAS norms (Williams, 1991).
      MMPI-2, BSI, BDI, POMS, and IES results indicate significant elevations on scales
      of depression, anxiety, anger, and posttraumatic stress disorder (PTSD) symptoms.
      The more brief tests of affect and mood appear sufficiently sensitive in
      measuring the dysphoric mood in group research studies. Clinical diagnoses using
      criteria from the Diagnostic and Statistical Manual of Mental Disorders, fourth
      edition (DSM-IV; American Psychiatric Association, 1994) criteria indicate a
      prevalence of 54% PTSD and 64% Amnestic or Cognitive disturbance. New onset of
      dermatological, respiratory, visual, and gastrointestinal symptoms and illnesses
      are consistent with the chemical exposure, the PTSD may be in reaction to it, and
      Amnestic/Cognitive disturbance, from both an organic and functional etiology.

PMID- 14590611
TI  - The expanded Trail Making Test: rationale, development, and psychometric
      properties.
AB  - Many procedures have been employed to determine the specific cognitive components
      necessary for successful Trail Making Test (TMT) performance. Yet, there is still
      considerable disagreement in the literature as to what these components might be.
      The present study explores an alternative methodology to address this problem. By
      systematically varying the stimuli within the TMT format, it may eventually be
      possible to isolate the cognitive demands of this test. As the first step toward
      this goal, two experimental forms of the TMT, forms X and Y, were developed and
      subjected to empirical validation. The results indicate that this Expanded Trail
      Making Test possesses adequate concurrent and criterion validity to support the
      proposed methodology. The results also suggest that the psychometric properties
      of the TMT format are robust to alterations in test stimuli. Secondary benefits
      of this methodology, in terms of explaining between-group variance and in terms
      of cross-cultural assessment, are discussed.

PMID- 14590612
TI  - Continuous Visual Memory Test performance in healthy persons 60 to 94 years of
      age.
AB  - Performance of elderly subjects on the Continuous Visual Memory Test (CVMT) was
      examined in a sample of neurologically normal adults (74 males and 103 females).
      Means for age and education were 71.20 years (SD = 6.02) and 14.77 years (SD =
      2.48). Results revealed that the recommended impairment cut-off scores provided
      in the CVMT manual did not generalize to the current sample with 8% to 50% of
      healthy elderly persons falling within the impaired range. Therefore, the current
      sample was used to provide updated preliminary elderly normative data for the
      CVMT.

PMID- 14590613
TI  - Working memory for nonverbal auditory information in dementia of the Alzheimer
      type.
AB  - Previous studies have revealed working memory impairments in individuals with
      dementia of the Alzheimer type (DAT) using visually and auditorily presented
      verbal materials, and visually presented nonverbal materials. Based on findings
      from behavioral and neuropathological studies, impairments in working memory for
      auditorily presented nonverbal materials have been hypothesized as well. Results
      of a study conducted by Kurylo, Corkin, Allard, Zatorre, and Growden (1993),
      however, failed to support this hypothesis. In the current investigation,
      perception and working memory for nonverbal auditory information (tones) were
      assessed using same-different discrimination tasks. Participants included
      individuals with no dementia, very mild DAT, and mild DAT. Unlike the findings
      from the study conducted by Kurylo and colleagues, our results suggest intact
      tone perception but a progressive decline in working memory for auditory
      nonverbal information with advancing DAT. A similar decline was also noted on a
      task assessing working memory for auditorily presented verbal information.

PMID- 14590614
TI  - A comparison of four tests of malingering and the effects of coaching.
AB  - This study examined the ability of four measures of suboptimal performance to
      correctly classify four groups of subjects (normal controls, uncoached
      malingering, coached malingering, and head injured). Only the Portland Digit
      Recognition Test-Computerized (PDRT-C) identified simulating malingerers with
      greater than chance accuracy while minimizing false positives. Coached subjects
      were better able than their uncoached counterparts to avoid detection on all
      measures. In an additional analysis, a discriminant function using the response
      latency and total correct scores from the PDRT-C identified 70% of the coached
      malingerers on cross validation. The three other tests (Nonverbal Forced Choice
      Test, 21-Item Test, and Dot Counting Test) failed to obtain a satisfactory
      classification rate for the malingering groups as a whole and coached malingerers
      in particular.

PMID- 14590615
TI  - In defense of the Halstead Reitan Battery: a critique of Lezak's review.
AB  - Since many neuropsychologists utilize the Halstead Reitan Battery (HRB), it is
      important to answer a critical review contained in Lezak's (1995) book. Lezak
      understands hypothesis testing but not HRB pattern analysis or the use of fixed
      batteries. A fixed battery provides a constant background, which reveals
      individual characteristics of the patient. Issues discussed include, types of
      batteries, legitimate review methods, and Reitan's method. This writing
      demonstrates that almost all of Lezak's criticisms of either the HRB or the
      Halstead Russell Neuropsychological Evaluation System (HRNES) are either
      incomplete, misleading or erroneous. Her critique of the Reitan method involved a
      confusion of terms. In spite of attempts to discredit the HRB not a single sound
      study questioning the validity of the HRB was presented, while many studies have
      demonstrated its validity. The fallacy of nonrefutation asserts that it is a
      fallacy to condemn methods that have been validated while recommending procedures
      that have not been validated. Lezak questions Reitan's method, the HRB and the
      HRNES, which have been thoroughly validated, while presenting no validating
      studies of her own recommended methods.

PMID- 14590616
TI  - The development of decoding of emotions in children with externalizing behavioral
      disturbances and their normally developing peers.
AB  - This investigation examined children's capacity to decode verbal and nonverbal
      emotional stimuli. Children with externalizing behavioral symptoms were compared
      to two types of controls, including chronically ill and normally developing
      children. Children were requested to identify whether video scenes were happy,
      angry, sad, or neutral, across four different modalities including verbal,
      prosody, facial, and combined. Findings were that chronological age was a
      significant predictor of children's ability to decode emotions with older
      children having better developed abilities than their younger peers. Verbal
      intelligence also was found to be a significant predictor of the ability to
      decode facial expressions and combined scenes. Although the data did not support
      the original hypotheses that children with externalizing behavior disorders would
      be less accurate than controls in the decoding of emotions, findings did support
      a developmental progression of decoding accuracy. Recommendations within the
      limitations of the study design are provided which support a developmental
      framework in children's acquisition of the decoding of emotions.

PMID- 14590618
TI  - Differential contributions of cognitive and motor component processes to physical
      and instrumental activities of daily living in Parkinson's disease.
AB  - Patients with Parkinson's disease (PD) become dependent upon caregivers because
      motor and cognitive disabilities interfere with their ability to carry out
      activities of daily living (ADLs). However, PD patients display diverse motor and
      cognitive symptoms, and it is not yet known which are most responsible for ADL
      dysfunction. The purpose of this study was to identify the contributions that
      specific cognitive and motor functions make to ADLs. Executive functioning, in
      particular sequencing, was a significant independent predictor of instrumental
      ADLs whereas simple motor functioning was not. By contrast, simple motor
      functioning, but not executive functioning, was a significant independent
      predictor of physical ADLs. Dementia severity, as measured by the Dementia Rating
      Scale, was significantly correlated with instrumental but not physical ADLs. The
      identification of selective relationships between motor and cognitive functioning
      and ADLs may ultimately provide a model for evaluating the benefits and
      limitations of different treatments for PD.

PMID- 14590617
TI  - Performance of normal adults on the Luria-Nebraska Neuropsychological Battery,
      form I.
AB  - To examine three problems in the interpretation of the Luria-Nebraska
      Neuropsychological Battery (LNNB), the normal participants from four different
      studies were pooled to form a sample of 241 LNNB profiles. The first problem
      addressed was the LNNB's false positive rate. All five yes/no decision rules were
      applied simultaneously. Each individual rule had a 0% to 8% false positive rate:
      combining the rules in four different ways increased the false positive rate by
      0% to 6%. When divided into over and under 65 years old groups, each rule applied
      to the younger group had a 0% to 5% false positive rate: combining them increased
      the rate to 6-8%. When applying the rules to the older group, each rule had a 0
      to 27% false positive rate: combining all rules but the one with the highest
      error rate produced a false positive rate of 27%. The false positive rate for the
      entire sample was 12%. To solve the second problem of interpretation, making
      qualitative item analyses easier, the difficulty level (i.e., percentage of
      normals missing the item) for each item was calculated. The third problem was the
      LNNB's malingering formula's accuracy. The formula was applied to the sample: as
      expected, the normal profiles had an inaccuracy rate of 26%. The few mildly
      impaired profiles had a 6% inaccuracy rate. When applied to the entire sample of
      normals and using the appropriate interpretive guidelines, the formula had a
      false positive rate of 1%.

PMID- 14590619
TI  - Factor analysis of four measures of prefrontal lobe functioning.
AB  - The Wisconsin Card Sorting Test, Stroop Test, Verbal Fluency (FAS), and Auditory
      Consonant Trigrams are commonly used measures of prefrontal lobe dysfunction.
      However, insufficient data are available regarding the specific functions
      assessed by these tests and the relationship of the tests to each other. These
      four tests, as well as measures of IQ, memory, attention, and processing speed,
      were administered to 250 subjects (138 patients and 112 controls). Factor
      analysis yielded three factors, and a higher order frontal lobe factor, using a
      dimensional factor analytic methodology. Present findings revealed modest
      correlations among the prefrontal tests, suggesting that the tests tap somewhat
      different abilities and are not redundant. Adequate assessment of prefrontal lobe
      abilities appears to require use of more than one test.

PMID- 14590620
TI  - Latent structure of the Wisconsin Card Sorting Test in a clinical sample.
AB  - The aims of this study were to: (a) examine the consistency of the published
      Wisconsin Card Sorting Test (WCST) factor structures; (b) determine the factor
      structure of the WCST in a large, heterogeneous sample; and (c) compare the WCST
      factor analytically with other neuropsychological procedures. Two WCST factors
      (concept formation/perseveration and Failure-to-Maintain-Set [FMS]) were
      consistently reported in the literature. Our analysis of data from 473 clinical
      cases replicated the two factors previously reported and revealed a third on
      which nonperseverative errors (NPE) was the sole salient variable. This pattern
      was maintained in three of four diagnostically distinct subgroups. These factors
      are potentially clinically meaningful, with each seeming to reflect one of three
      qualitatively different performance styles. In the construct validation factor
      analysis, WCST scores loaded independently of other neuropsychological variables,
      indicating that the WCST contributes uniquely to neuropsychological evaluation.
      Nevertheless, despite the rational interpretation of the factors, the cognitive
      processes underlying WCST performance remain poorly understood. Future directions
      for the application of these factor analytic findings are discussed.

PMID- 14590621
TI  - Validity of the Wonderlic Personnel Test as a brief measure of intelligence in
      individuals referred for evaluation of head injury.
AB  - Some have argued that the Wonderlic Personnel Test (WPT) may represent a brief
      and efficient measure of intellectual functioning (e.g., Dodrill, 1980). The
      present study investigated the validity of the WPT as such a measure, in
      individuals with head injury. The findings suggested that, although the WPT
      showed relatively high agreement with the Wechsler Adult Intelligence Scale
      Revised (WAIS-R) in the whole group, it did not have good agreement with WAIS-R
      scores on an individual case basis. Since clinical practice typically seeks to
      evaluate individual performance, it is suggested that the WPT is not a suitable
      tool for psychological assessment of individuals with known or suspected head
      injury.

PMID- 14590622
TI  - Test-retest stability of the Continuous Visual Memory Test in elderly persons.
AB  - Ninety-two normal elderly persons were administered the Continuous Visual Memory
      Test (CVMT) on two occasions an average of 1.1 years apart. Means for age and
      education were 69.02 years (SD = 5.79) and 14.80 years (SD = 2.64), respectively.
      Stability coefficients were.49 on the Total score,.44 on d-prime, and.48 on
      Delayed Recognition. D-Prime and Delayed Recognition scores demonstrated
      significant change on retest. To assist clinicians in the process of detecting
      meaningful change on retest, standard error of difference values and 90% cut-off
      scores were provided.

PMID- 14590623
TI  - The Hopkins Verbal Learning Test and CVLT: a preliminary comparison.
AB  - A preliminary examination of the relationship between two clinical measures of
      verbal memory was conducted among healthy older subjects. Correlations between
      selected scores from the Hopkins Verbal Learning Test (HVLT) and the California
      Verbal Learning Test (CVLT) revealed that the total number of words learned
      across trials for both tests were significantly related (r =.74, p <.001), while
      there was no association between error rates (i.e., perseverations and
      intrusions). Recognition hits alone were not related, but recognition
      discriminability indices (accounting for false-positive errors) on the two
      measures were significantly correlated (r =.46, p =.02). While the HVLT appears
      to adequately assess basic verbal learning capacity, its utility in assessing
      some of the more complex and qualitative aspects of verbal learning and memory
      function may be limited, and interpretations of HVLT performances based on the
      CVLT literature must be made with caution. A clinical case example is presented
      to illustrate some of the issues in comparing performance on the HVLT and CVLT.

PMID- 14590624
TI  - Clinical use of the Benton Visual Retention Test for children and adolescents
      with learning disabilities.
AB  - This study examined the Benton Visual Retention Test (BVRT) with 130 children and
      adolescents with learning disabilities (LD) who were between the ages of 8 and 13
      years of age. Results of factor analysis showed errors scores from the BVRT
      loaded on a visual processing/memory factor. The measure appears to be sensitive
      to developmental patterns which was supported by statistical analysis. Error and
      correct score patterns are also examined for different subgroups. The results of
      this study support the use of the BVRT with children and adolescents with LD.

PMID- 14590625
TI  - Utility of a seven-subtest version of the WAIS-R among an Alzheimer's disease
      sample.
AB  - Recent health care sector changes have created a need for shorter, more focused
      neuropsychological assessments. The WAIS-R provides useful information on
      patients' general cognitive abilities, but poses problems in that it is time
      consuming and may contribute to fatigue, especially among geriatric patients with
      dementia. This study evaluated Ward's (1990) 7-subtest version of the WAIS-R
      among 32 patients with presumptive Alzheimer's disease. Among all patients, the
      abbreviated test underestimated full WAIS-R scores by an average of 2.0, 0.2, and
      1.8 points for the Verbal Intelligence Quotient (VIQ), Performance Intelligent
      Quotient (PIQ), and Full-Scale Intelligence Quotient (FSIQ). This general finding
      held true regardless of whether scores were generated using the standard WAIS-R
      method (for patients age 75 and younger) or using age corrections (i.e., Mayo
      Older Americans' Normative Studies [MOANS]) for older patients. Most patients
      scored within the mean standard errors of measurement defined in the WAIS-R
      manual for VIQ, PIQ, and FSIQ. In general, the 7-subtest and full versions of the
      WAIS-R yielded similar findings among this closely screened sample, but further
      testing among a more typical sample of patients with multiple risk factors for
      dementing conditions is needed.

PMID- 14590626
TI  - Neuropsychological test performance in illiterate subjects.
AB  - The purpose of this study was to further analyze the effects of education across
      different age ranges on neuropsychological test performance. Two different
      analyses were performed. The first analysis was conducted in order to pinpoint
      the impact of school attendance on neuropsychological testing. A group of 64
      illiterate normal subjects was selected in the Mexican Republic. Their
      performance was compared with two barely schooled control groups (1-2 and 3-4
      years of schooling). The subjects' ages ranged from 16 to 85 years. In the second
      analysis, the illiterate subjects were further matched by age and sex with
      individuals with 1 to 4, 5 to 9, and 10 to 19 years of formal education. The
      Spanish version of the NEUROPSI neuropsychological test battery (Ostrosky,
      Ardila, & Rosselli, 1997) was used. Results indicated a significant educational
      effect on most of the tests. Largest educational effect was noted in
      constructional abilities (copying of a figure), language (comprehension),
      phonological verbal fluency, and conceptual functions (similarities, calculation
      abilities, and sequences). Aging effect was noted in visuoperceptual (visual
      detection) and memory scores. In the first subject sample, it was evident that,
      despite using such limited educational range (from 0-4 years of formal
      education), and such a wide age range (from 16-85 years), schooling represented a
      stronger variable than age. It is proposed that education effect on
      neuropsychological test performance represents a negatively accelerated curve,
      tending to a plateau.

PMID- 14590627
TI  - Frontal lobe functioning in man: the riddle revisited.
AB  - Forty-eight patients, each with a single frontal lobe lesion, were tested with a
      battery of 10 of the most widely used neuropsychological tests, comprising five
      traditional "frontal" tests and five others, for which that claim is not
      generally made. All correlations among the tests in the group were positive and
      significant. Moreover, the average correlation between each frontal test and the
      other tests in the frontal group was found to be higher than the average
      correlation of the same frontal test with the tests in the other group. A factor
      analysis of the scores on the five frontal tests yielded a single factor
      accounting for 53% of the variance. A factor analysis on the entire battery of
      tests (frontal plus nonfrontal) also yielded a strong general factor; although
      this accounted for a smaller portion (43%) of the shared variance, and one test
      (Verbal Span) failed to show a substantial loading on the factor. Neither the
      results of the present study nor the findings of other researchers argue for the
      abandonment of the concept of "executive" functioning, mediated by the
      functioning of the frontal lobes, in favor of a variant of fractionation.

PMID- 14590628
TI  - Potential impact of age- and education-corrected scores on HRNB score patterns in
      participants with focal brain injury.
AB  - Heaton, Grant, and Matthews (1991) presented an alternate scoring system for the
      Halstead-Reitan Neuropsychological Battery (HRNB) using age-, education-, and
      gender-corrected T scores to replace the raw score system traditionally employed
      with the test. This study addressed the impact of using this system on the score
      patterns generated by the HRNB in 64 clients with localized injuries to one of
      four quadrants of the brain. Results showed that the raw scores show more overall
      impairment than do the T scores, but overall the systems are statistically equal
      in their ability to separate the localized groups. The patterns of differences
      among the systems also differ. Although these findings suggest overall
      equivalence of the systems, they also show that each may have strengths that will
      show up in different analyses. A process of using both scoring systems for their
      own unique information is advocated as most appropriate at the current time until
      additional research addresses the questions raised in this study and elsewhere.

PMID- 14590629
TI  - Neurobehavioral symptoms and family functioning in traumatically brain-injured
      adults.
AB  - Traumatic brain injury (TBI) often results in a myriad of symptoms across
      physical, cognitive, and neurobehavioral domains. Despite inherent limitations
      associated with physical or cognitive impairments, the extant literature suggests
      that neurobehavioral symptoms tend to be the most distressing symptoms for the
      family and are more strongly related to poor outcome for the patient. The
      Neuropsychology Behavior and Affect Profile (NBAP) along with the General
      Functioning subscale of the Family Assessment Device (FAD-GF) and the Perceived
      Stress Scale were administered to 153 family members of persons who had sustained
      a TBI. The results provide new normative data and statistical support for the
      NBAP as a promising measure of neurobehavioral symptomatology following TBI. The
      correlation of.54 (p <.01) between FAD-GF and Full Scale NBAP scores provides
      powerful support for the hypothesis that family dysfunction is related to the
      presence of neurobehavioral symptoms in the patient. NBAP domains of Depression,
      Inappropriateness, Pragnosia, and Indifference appear most strongly related to
      family functioning and also bear a significant relationship to caregiver stress
      level and patient unemployment, whereas injury severity had little impact on
      either family functioning or neurobehavioral symptoms. The findings reinforce the
      significance of neurobehavioral symptoms and fortify their proposed link to
      family dysfunction post-TBI.

PMID- 14590630
TI  - Wisconsin Card Sorting Test performance in above average and superior school
      children: relationship to intelligence and age.
AB  - This study explores the relationship of intelligence and age to scores on the
      Wisconsin Card Sorting Test, a measure of executive function. A sample of 26
      normal children with Wechsler Intelligence Scale for Children-III (WISC-III) Full
      Scale IQS above 130 and 24 normal children with WISC-III Full-Scale IQS between
      110 and 129 were administered the test. A comparison to published norms revealed
      that above average children outperformed the average 9- to 14-year-old child on
      every measure at every age. Multiple regression analyses statistically related
      the Wisconsin Card Sorting Test, perseverative, nonperseverative, total errors,
      and trials to the first category of intelligence. Intelligence proved to be a
      significant qualifier of age trends. Gender relationships were nonsignificant in
      a preliminary analysis.

PMID- 14590631
TI  - Neuropsychological similarities and differences among Huntington's disease,
      multiple sclerosis, and cortical dementia.
AB  - A comparison of cognitive function was made among patients with Huntington's
      disease, multiple sclerosis, and cortical dementia. Utilizing indexes from the
      Wechsler Adult Intelligence Scale and the Halstead-Reitan Battery, it was found
      that there was substantially more severe cognitive deficit in the Huntington's
      disease patients than in the multiple sclerosis patients, and the level of
      impairment was similar between the Huntington's disease and cortical dementia
      groups. Qualitative differences, particularly involving amount and type of
      perseveration, were noted among the three groups. It was concluded that
      subcortical dementia is not necessarily characterized by mild cognitive
      impairment, and there appear to be important qualitative differences between
      cortical and subcortical dementia. Results are discussed in terms of the
      usefulness of the presently conceptualized distinction between cortical and
      subcortical dementia.

PMID- 14590632
TI  - Long-term neuropsychological sequelae of severe burns.
AB  - Eight patients who suffered severe burns and protracted periods of amnesia
      following those burns were evaluated for neuropsychological and neuropsychiatric
      problems between 6 months and 4 years following their accidents. All were found
      to have significant problems as evidenced in neuropsychological testing,
      activities of daily living, and reports from relatives. Findings on these burn
      patients with postburn amnesia were quite different from those of five burn
      patients who did not develop amnesia. Problems observed and reported in the burn
      amnesia patients appeared to reflect clear neuropathological etiologies, which
      was not unexpected because their initial amnestic syndromes must also have been
      the result of significant central nervous system dysfunction. It is recommended
      that severe burn patients have neuropsychological, psychiatric, and neurological
      exams as part of routine postburn care.

PMID- 14590633
TI  - Quantitative and qualitative performance of stroke versus normal elderly on six
      clock drawing systems.
AB  - The utility of the Clock Drawing Test (CDT) in localizing lesions has not been
      thoroughly examined to date. In the present study, six scoring systems (Freedman
      et al., 1994; Ishiai, Sugishita, Ichikawa, Gono, & Watabiki, 1993; Mendez, Ala, &
      Underwood, 1992; Rouleau, Salmon, Butters, Kennedy, & McGuife, 1992; Sunderland
      et al., 1989; Tuokko, Hadjistavropoulos, Miller, & Beattie, 1992; Watson, Arfken,
      & Birge, 1993; Wolf-Klein, Silverstone, Levy, & Brod, 1989) were used to assess
      clock drawings by 76 stroke patients and 71 normal controls. Significant
      differences were found between normals and stroke patients on all scoring systems
      for both quantitative and qualitative features of the CDT. Quantitative indices
      were not helpful in differentiating between various stroke groups (left versus
      right versus bilateral stroke; cortical versus subcortical stroke; anterior
      versus posterior stroke). Qualitative features were helpful in lateralizing
      lesion site and differentiating subcortical from cortical groups. Correlational
      analyses revealed that CDT performance was related to visuospatial processing and
      measures commonly used in cognitive screening.

PMID- 14590634
TI  - Base rates of "impaired" neuropsychological test performance among healthy older
      adults.
AB  - Base rates of deficient neuropsychological test performance were evaluated among
      132 neurologically healthy older normal adults using a variety of measures
      commonly employed in the "flexible-battery"approach to neuropsychological
      assessment. Subjects were divided into three age groups (50 to 59, 60 to 69, and
      70 to 79 years). Despite the healthy status of our sample, most tests yielded at
      least some proportion of subjects earning scores in the borderline and impaired
      ranges (1.3 and 2.0 standard deviations below the age-group mean, respectively).
      Across the battery of measures, 73% of subjects earned a borderline score on at
      least one measure, and 20% of subjects earned at least two scores in the impaired
      range on separate tests. The proportion of subjects consistently earning
      borderline or impaired scores across multiple measures within specific cognitive
      domains was generally lower. Results illustrate the problems in interpreting
      isolated low scores, and the need to consider false-positive base rates in
      drawing inferences from poor test performance.

PMID- 14590635
TI  - Neuropsychologic impairment in patients with nonepileptic seizures.
AB  - Patients with nonepileptic seizures (NES), those with epileptic seizures (ES),
      and normal controls were compared on a battery of neuropsychologic tests.
      Diagnoses were made after intensive electroencephalogram (EEG) monitoring.
      Excluded from the study were patients with both ES and NES, as well as patients
      with ES who had evidence of structural brain damage. On all neuropsychologic
      measures, the two seizure groups were significantly impaired relative to the
      controls, but there were no significant differences between the ES and NES group
      performances. Additional neuropsychologic measures were obtained on the two
      seizure groups but not controls, and again there were no significant differences
      between the two seizure groups. Further analyses suggested that the NES group's
      impairment was related to emotional factors. The Minnesota Multiphasic
      Personality Inventory (MMPI)/MMPI-2 and the Portland Digit Recognition Test were
      helpful in classifying patients by seizure group. Our results, which are
      consistent with those of previous studies, suggest that neuropsychologic
      abnormalities are not pathognomonic of brain dysfunction in this population.
      However, the Portland Digit Recognition Test (PDRT) and measures of personality
      are useful for classification purposes in the differential diagnosis of epileptic
      and nonepileptic seizures.

PMID- 14590636
TI  - Ecological validity of neuropsychological tests: focus on the California Verbal
      Learning Test and the Wisconsin Card Sorting Test.
AB  - To date, few studies have assessed the ecological validity of current measures of
      memory and executive functioning, particularly the California Verbal Learning
      Test (CVLT) and the Wisconsin Card Sorting Test (WCST). A battery of tests,
      including the CVLT and the WCST, was administered to 28 severely head-injured
      adults who were 1 year or more postinjury. Hierarchical linear regression was
      performed to assess the relationship between these cognitive tests and work
      functioning while statistically controlling for physical disability, emotional
      distress, and memory compensation strategies utilized by the participants.
      Results suggest that the CVLT was best at predicting performance on the job;
      however, the CVLT and the WCST were about equally predictive of the type of
      position held by a participant. Hence, this study demonstrates the ecological
      validity of measures of memory and executive functioning for predicting work
      related skills.

PMID- 14590637
TI  - MMPI/MMPI-2: comparisons of amnesic patients.
AB  - The amnesic population provides a unique opportunity to examine the reliability
      of clinical tests because amnesics do not consciously recollect initial testing
      sessions. In this study, amnesic subjects were studied to examine the reliability
      between the Minnesota Multiphasic Personality Inventory (MMPI) and the MMPI-2.
      Findings indicated that there were no statistical differences between versions of
      the MMPI and further revealed that many of the scales were significantly
      correlated. Amnesic patients produced elevated scores on subscales two
      (depression) and eight (schizophrenia), not unlike various other groups of
      neurologically impaired individuals. This indicates that MMPI and MMPI-2 scores
      in these patient populations may reflect the medical and psychosocial effects of
      brain damage rather than premorbid personality dysfunction. A close evaluation of
      amnesics' performance, in conjunction with the critical items they endorsed,
      offers insight into the personality traits of the amnesic patient population. The
      relative stability of performance across personality tests administered over
      several weeks is relevant to the formation and stability of the amnesic's concept
      of self.

PMID- 14590639
TI  - Personality change in head trauma: a validity study of the Neuropsychology
      Behavior and Affect Profile.
AB  - This study represents the first attempt to cross validate and report on the
      Neuropsychology Behavior and Affect Profile (NBAP) using closed head injury (CHI)
      participants. The NBAP is designed to measure emotional functioning before and
      following a brain event. Two CHI samples, differing primarily by method of
      ascertainment, were compared to a group of normal controls. Results provided
      support for concurrent and predictive validity of the NBAP across both CHI
      samples. Significantly higher levels of postinjury emotional functioning in
      clinic-referred CHI patients compared to CHI individuals not seeking treatment
      (strictly research participants) was demonstrated. A surprising finding was that
      pre-injury emotional levels of clinic-referred subjects were rated as less severe
      than that of controls. Based on this finding, the possibility of a gradient
      effect was discussed in which raters appeared to place selectively greater weight
      on current condition, while simultaneously making premorbid levels less severe
      than they really were. Results were discussed in the context of study limitations
      and directions for further research.

PMID- 14590638
TI  - Application of the Postconcussive Syndrome Questionnaire with medical and
      psychiatric outpatients.
AB  - The Postconcussive Syndrome Questionnaire (PCSQ; Lees-Haley, 1992) was previously
      found (Axelrod, Fox, Lees-Haley, Earnest, Dolezal-Wood, & Goldman, 1996) to
      produce four factors, named Psychological, Somatic, Cognitive, and Infrequency.
      These four factors of the questionnaire were evaluated across five groups of
      medical and psychiatric outpatients. The patients were from neurology, mental
      health, family practice, and internal medicine clinics as well as from a clinic
      that evaluated new patients to a health maintenance organization. Mental health
      patients had greater psychological symptoms and fewer health concerns than the
      other groups. Neurology patients differed from the other groups by having greater
      Infrequency symptoms. Patients who were referred for their screening evaluation
      or were seen by internal medicine had fewer overall symptoms than the other three
      patient groups. The data from this study provide support for the use of the PCSQ
      as a multifactorial self-report measure of symptom presentation.

PMID- 14590640
TI  - Discriminant function analysis of malingerers' and neurological headache
      patients' self-reports of neuropsychological symptoms.
AB  - Interpretation of a patient's neuropsychological examination involves the
      determination of the role motivational and psychiatric factors may have played.
      The ability to detect malingering becomes crucial, particularly when the
      examination occurs as a result of litigation. Moreover, falsely identifying a
      performance as distorted has serious consequences for the patient. The present
      study was conducted to replicate previous research that discriminated between
      malingered and nonmalingered responses to a neuropsychological self-report
      inventory. An overall hit rate of 84% for malingerers and neurologic headache
      patients demonstrated replication of the inventory's ability to identify
      malingerers. Of those predicted to be malingerers, 27% were false positives
      indicating the need to use this inventory in conjunction with other
      neuropsychological measures.

PMID- 14590641
TI  - The Affective Auditory Verbal Learning Test: peripheral arousal correlates.
AB  - The present study assessed the usefulness of the affective list alternatives to
      the Rey Auditory Verbal Learning Test (RAVL) in the induction of physiological
      arousal. It was anticipated that affective verbal learning would lead to arousal
      patterns characteristic of different emotions (Izard, 1977), with significant
      increases in blood pressure following negative list learning and significant
      decreases following positive list learning. Since diastolic blood pressure
      increased significantly following the learning of negatively valanced words and
      decreased significantly following the learning of positively valanced words, this
      was supported. Given the abundance of research on lateral asymmetries in
      emotional and verbal processing, the affective list alternatives to the RAVL may
      provide an objective means for evaluating individual differences in affective
      verbal learning as well as the induction of emotion. The Affective Auditory
      Verbal Learning Test (AAVL) may potentially provide a tool for assessment of
      cerebral dysfunction in the clinic or in the assessment of affective disorders.

PMID- 14590642
TI  - A review of the neuropsychological effects of commonly used prescription
      medications.
AB  - The practice of clinical neuropsychology has traditionally accorded limited
      attention to the impact of prescription medications on cognitive functioning.
      Though neuropsychologists see a wide array of patients with cerebropathologic and
      other organ system disease that are under pharmacotherapy, systematic attention
      to how these compounds potentially affect neuropsychological functioning has
      lagged. Psychomotor functioning, concentration, and memory are the most common
      cognitive domains negatively affected by such medications. In general sedative,
      psychomotor, and, to a lesser extent, attention/concentration effects covary and
      typically show tolerance with sustained drug administration. Memory effects are
      more resistant probably due to ongoing anticholinergic effects and the
      established link between the cholinergic system and memory functioning. This
      review covers the basic science and clinical literature addressing
      neuropsychological functioning both in healthy nonpatients and in patients
      treated with antidepressants, anxiolytics, stimulants, antihypertensives,
      antiepileptics and antihistamines. Critical to the understanding of the effects
      of these agents is the integration of multiple factors that modulate medication
      induced neurocognitive effects, such as chronicity of treatment, tolerance, age,
      ethnicity, metabolic capacity, psychological, and neurological disorders in the
      patient, and the benefits of successful treatment of these disorders.

PMID- 14590643
TI  - The Tower of London(DX): a standardized approach to assessing executive
      functioning in children.
AB  - In the current study, the Tower of London (Shallice, 1982) was modified to
      enhance its clinical utility as a measure of childhood executive functioning. The
      Tower of London-Drexel (TOL(DX)) was administered to normal control (NC; N = 56)
      and attention-deficit hyperactivity disorder (ADHD; N = 99) children (ages 7 to
      12) to determine whether age-related changes in performance were evident, to
      gather normative data, and to evaluate the test-retest reliability and criterion
      validity of the measure. The results revealed age-related changes in score
      performance, age-group normative data, an acceptable level of reliability and
      significant differences in performance of NC and ADHD subjects. Further,
      discriminant analysis classification rates determined that the TOL(DX) was
      sensitive and highly specific to ADHD. Implications and limitations of the study
      are discussed.

PMID- 14590644
TI  - Neuropsychological functioning of inmates referred for psychiatric treatment.
AB  - This article describes the Neuropsychological (NP) functioning of 71
      psychiatrically hospitalized male prisoners. Demographic description, patterns of
      drug use, patterns of violence, psychiatric diagnosis, and performance on the
      Halstead-Reitan Neuropsychological Battery (HRNB) are described. Using age and
      education adjusted norms (Heaton, Grant, & Matthews, 1991), 84% of this sample
      demonstrated impairment on the Halstead Impairment Index. Sensory Exam-Left,
      Tapping Dominant and Non-Dominant, Speech Perception, Tactual Performance Test
      Times/Memory/and Location, Trailmaking A and B, and Category Test were all
      impaired. Multivariate Analyses (MANOVAS) demonstrated significantly impaired
      performance on tasks of Motor, Psychomotor, and Reasoning, with FTT-Dominant, TPT
      Total, and Category Test contributing the most meaningful contribution to the
      multivariate effect. Varimax Rotated Principle Components Analysis revealed a
      five-factor model (Motor, Learning, Attention, Abstraction, and Processing
      Speed), which accounted for 69.9% of the total variance. Need for further
      research, and implications for the use of this information in developing
      treatment programs for psychiatrically disturbed prisoners are discussed.

PMID- 14590645
TI  - The relationship between ethnicity and word fluency.
AB  - The impact of ethnicity on word fluency measures, i.e., the FAS (Benton &
      Hamsher, 1976) and Animal Naming (AN) (Spreen & Strauss, 1991) tests, was
      explored. The groups included: White (n = 200), Black (n = 200), and Hispanic (n
      = 200) veterans. Multivariate analysis of variance (MANOVA) revealed significant
      main effects for FAS and AN total scores both before and after covarying for
      income, education, and Wide Range Achievement Test-Revised Reading scores (p
      <.05). The largest unadjusted group mean difference approximated a medium effect
      size. No differences were found between FAS and AN standardized scores within
      each group. The findings are discussed as they relate to clinical practice and
      research.

PMID- 14590646
TI  - A cross-validation study of the Victoria Revision of the Category Test.
AB  - Short form versions of the Category Test have been shown to be effective tools
      for assessing brain injury in relatively short amounts of time. The purpose of
      the current study was to compare the Victoria Revision of the Category Test with
      the full booklet version. The Victoria Revision short form was administered as
      part of a neuropsychological battery to two sets of participants matched for
      diagnosis. Results showed that the Victoria Revision is as effective in
      identifying brain injury as the full Category Test. The authors conclude that the
      Victoria Revision is a viable alternative to the full Category Test. In this time
      of managed health care, and in consideration of the fatigability of brain injured
      subjects, a valid short version of the Category Test is clinically relevant and
      useful.

PMID- 14590648
TI  - Judgment pitfalls in estimating premorbid intellectual function.
AB  - Neuropsychological diagnosis first requires estimation of patients' premorbid
      cognitive ability. Although a number of methods have been proposed for this
      purpose, in practice there is little standardization. Often, clinical judgment
      and expert synthesis of multiple sources of information are prescribed to derive
      a premorbid estimate. There are, however, a number of systematic biases in human
      cognition that may lead clinicians to produce inaccurate estimates of premorbid
      function. This paper reviews the cognitive biases that are most likely to
      interfere with clinical judgment in this context. Given findings in the human
      judgment literature, actuarial strategies are recommended to avoid the
      contamination of cognitive bias.

PMID- 14590649
TI  - Methods of estimating premorbid functioning.
AB  - Clinical neuropsychological assessment frequently requires the comparison of
      obtained scores against some estimate of premorbid level of functioning, but only
      recently has significant attention been turned to objective methods to accomplish
      this objective. Clinical judgment, although useful in some circumstances, is
      generally insufficient. Other methods of estimating premorbid function include
      demographic regression formulae, such as the Barona formula, subtest scatter
      methods, such as that suggested by Lezak, and the use of current scores on tests
      of presumably spared abilities, such as the National Adult Reading Test (NART).
      Almost all methods predict to some general level of intellectual functioning
      rather than to specific neuropsychological skills. This paper reviews the
      suggested methods in terms of the underlying assumptions and the available
      empirical evidence. Suggestions for future research include the development of
      skill specific predictors as well as investigations regarding the relation
      between predictor accuracy and characteristics of the subject, such as high
      versus low premorbid functioning in the subject. Additionally, there is a great
      need for methods to predict premorbid functioning in children.

PMID- 14590650
TI  - Neuropsychologists' practice patterns in assessing premorbid intelligence.
AB  - The current study surveyed practicing neuropsychologists about the methods they
      use to estimate premorbid levels of function, and their prior training with these
      methods. Doctoral level psychologists, who are members of the National Academy of
      Neuropsychology, were sent a questionnaire developed by the authors to assess
      these variables. Findings suggest that there is relatively little use of
      strategies specifically designed to assess premorbid ability. Demographics and
      training were not associated with methods used. Over one third of the respondents
      indicated that they believed their formal training had not been adequate in
      helping them to address this issue.

PMID- 14590651
TI  - The prediction of premorbid memory ability.
AB  - An estimation of premorbid memory ability is necessary for clinical judgments of
      memory status following brain injury or illness. This paper describes the nature
      of clinical reasoning about memory ability and intelligence. The analysis of
      these reasoning problems has progressed from the simple contrast of clinical
      versus actuarial models to a theory that integrates all such models as
      applications of reasoning under uncertainty. This is followed by the first
      empirical study of the estimation of premorbid memory ability from demographic
      variables. The results of this analysis clearly suggest that demographic
      variables predict memory scores at a low level (R =.45); this result stands in
      contrast to the higher predictive power of demographics when IQ is the criterion.
      Practical suggestions are then proposed for establishing an empirical basis for
      clinical judgments of premorbid memory ability.

PMID- 14590652
TI  - Clinical utility of Wechsler Memory Scale-Revised and predicted IQ discrepancies
      in closed head injury.
AB  - Comparisons between Wechsler Memory Scale-Revised (WMS-R) indexes and Wechsler
      Adult Intelligence Scale-Revised (WAIS-R) IQ scores have been proposed to
      identify severity of memory deficits. However, many neurologic conditions reduce
      both intellectual and memory functioning, and thus, examining differences between
      these scores may be of little value. Closed head injured subjects who completed
      the WMS-R were divided into either mild injury (MI, n = 41) or moderate/severe
      (SI, n = 41) injury groups based on trauma severity indicators and were matched
      on age and level of education. The Oklahoma Premorbid Intelligence Estimation
      (OPIE), a regression formula that takes into account demographic variables as
      well as IQ performance, was calculated for each subject. Discrepancy scores were
      calculated between predicted IQ scores and WAIS-R IQ and WMS-R indexes. SI head
      injured subjects displayed significantly larger discrepancies (19 points) between
      OPIE scores and Delayed Recall Indexes from the WMS-R than the MI subjects (10
      points). Significantly larger percentages of subjects in the SI group displayed
      significant (>SD) reductions in many of the WMS-R and WAIS-R scores from
      estimates than subjects in the MI group. Comparing current memory functioning to
      estimates of premorbid intellectual ability appears to be a sensitive indicator
      of presence and degree of intellectual and memory dysfunction in head trauma
      patients. Results also provide evidence that estimates of premorbid intellectual
      ability can serve as estimates of premorbid memory functioning.

PMID- 14590653
TI  - Clinical aspects and issues in assessing premorbid IQ and cognitive function.
AB  - Clinical approaches to estimation of preinjury IQ are and will continue to be
      important to neuropsychologists, especially those involved in the forensic arena.
      Forensic approaches require not only defensible and demonstrable theoretical and
      empirical bases; they also require face validity for procedures used for
      establishing putative preinjury mental functional status. Procedures found to be
      of value for such purposes include postinjury residual skill levels; predictions
      based on residual functional levels on abilities resistant to injury; and mental
      requisites of preinjury academic, vocational, and avocational activities. Ideally
      and fairly typically, it is possible to demonstrate good congruence among those
      procedures in fashion conductive to informed decision making by the courts.

PMID- 14590654
TI  - Postscripts on premorbid ability estimation: conceptual addenda and a few words
      on alternative and conditional approaches.
AB  - The estimation of premorbid ability levels has been debated for some time. Some
      of the difficult issues involved are reviewed here and comments provided on
      certain approaches, some of which tend to be popular for reasons of convenience
      and false beliefs of their accuracy, and some that are less well-known.
      Demographic estimation procedures in particular tend to fare better than believed
      in some research. An additional approach is recommended for further research, one
      that is equally applicable to children and adults, and that takes maximum
      advantage of the known relationships among IQ and genetic and environmental
      variance in intellectual development.

PMID- 14590655
TI  - Suspected malingering and the Digit Memory Test: a replication and extension.
AB  - This study replicated a previous finding that suspected malingerers often perform
      at a level worse than patients with unequivocal brain dysfunction on the Digit
      Memory Test (DMT). In addition, it was demonstrated that patients suffering from
      aphasia as well as temporal and "frontal lobe" damage perform at a level higher
      than suspected malingerers. DMT performance of patients with true dementia,
      however, may be difficult to distinguish from suspected malingerers. If an
      individual is not demented (as judged by such tests as the BNI Screen for Higher
      Cerebral Functions) and performs at a level less than 95% across three trials of
      the DMT, the question of noncooperation with testing procedures or "malingering"
      should be considered.

PMID- 14590656
TI  - Performance of Parkinson's disease patients on the Visual Search and Attention
      Test: impairment in single-feature but not dual-feature visual search.
AB  - Nondemented patients with Parkinson's disease (PD) and a group of age and
      education matched controls were administered a modified version of the Visual
      Search and Attention Test (VSAT). This task measures subjects' speed at
      localizing letter or symbol targets based on either a single-feature or a dual
      feature search. Three indices were derived from the VSAT: (a) the amount of time
      taken to complete each of the trials (completion time), (b) the number of target
      items not crossed out (omissions), and (c) the number of nontarget items crossed
      out (commissions). The results indicated that, in terms of completion time, the
      PD patients were impaired on the single-feature search conditions but not on the
      dual-feature search conditions, suggesting that PD patients are impaired in
      selective attention processes. It was also found that the number of target items
      omitted by the normal controls on the VSAT varied as a function of the nature of
      the target (letter or form) and the search requirements (single-feature or dual
      feature search), whereas the number of targets omitted by the PD patients was not
      affected by these factors. Correlational analyses suggested that the three
      measures derived from the VSAT assessed different components of attentional
      performance in these patients. Overall, the results of this study suggest that
      the VSAT can be used to detect subtle attentional impairments in nondemented PD
      patients, and that the pattern of their impairment on this clinical test is
      similar to that found on experimental attentional measures.

PMID- 14590658
TI  - Assessing family involvement in traumatic brain injury rehabilitation: the
      development of a new instrument.
AB  - A measure for assessing family involvement in traumatic brain injury
      rehabilitation (TBI) was developed. The Family Involvement Assessment Scale
      (FIAS) is theoretically based on Barrer's (1988) model of family involvement in
      TBI rehabilitation, which highlights two dimensions, "support" and "involvement."
      An initial pool of 337 items believed to be related to the constructs of
      "support" and "involvement" was generated. Forty-nine items were systematically
      selected from the initial pool and included in a preliminary assessment form in
      which 172 professionals rated the items on the dimensions of support and
      involvement. Eleven items were subsequently eliminated from the original pool
      based on these ratings. The remaining 38 items were used by 181 of the
      professionals to evaluate the involvement of actual family members of patients
      receiving TBI rehabilitation services in their programs. A factor analysis was
      performed on a remaining pool of 38 items. Three factors with an eigenvalue
      greater than 2.0 accounted for 48.8% of the total variance. One item that did not
      significantly load on any of the factors was eliminated. The FIAS includes a
      final set of 37 items, comprised of three subscales based on the factor analysis.
      Two of the scales, the Involvement-Rehabilitation (IR) scale and the Support (S)
      scale correspond, respectively, to Barrer's (1988) dimensions of "involvement"
      and "support." The third scale, Involvement-Patient (IP), is a unique construct
      that measures the degree to which a family member is involved in the
      rehabilitation process with respect to their involvement and relationship with
      the patient. The three scales yielded adequate internal reliabilities.
      Correlation coefficients between the scales indicated that the IR and S scale are
      not statistically related, but the IP scale is significantly related to both the
      IR and S scales. Interrater and test-retest reliability, and concurrent and
      predictive validity for the FIAS are still to be determined.

PMID- 14590657
TI  - Accuracy of self-reported educational attainment among diverse patient
      populations: a preliminary investigation.
AB  - Despite speculation concerning the accuracy of self-reported information,
      particularly from certain patient populations, many neuropsychologists continue
      to estimate premorbid intellectual functioning on the basis of self-reported
      educational attainment. This study examined 116 individuals with diverse
      diagnoses [i.e., alcoholism, posttraumatic stress disorder (PTSD), schizophrenia
      or schizoaffective, and dementia] to determine the accuracy of their self
      reported high school educational attainment. Results suggest that at least half
      of all participants were inaccurate as defined by discrepancies between actual
      and estimated GPA greater than.5 on a traditional 4-point grading scale. Most
      patients were inaccurate in the direction of overestimating their educational
      attainment. Patients diagnosed with alcoholism and PTSD were significantly less
      accurate in recalling their educational history when compared to a group of
      normal-control subjects. Several subjects, whose records could not be verified,
      were found to have not attended high school as they had claimed. These results
      underscore the potential inaccuracy that exists when estimating premorbid
      intelligence using self-reported information.

PMID- 14590659
TI  - Deterioration in the production of verbal and nonverbal material as a function of
      time is contingent upon the meaningfulness of the items.
AB  - The performances of 100 university students were compared for their levels of
      production on fluency tests for verbal and nonverbal material that was
      manipulated to be meaningful or nonsense. For both the meaning conditions there
      was a significant deterioration in performance as a function of time, while
      production of the nonsense items remained constant. The results are consistent
      with the notion that the obligation for the items on the Verbal Fluency Test to
      be meaningful may require that the subject draws on the available word store,
      resulting in deterioration of performance as this word store is exhausted.

PMID- 14590660
TI  - Cognitive functioning in alcoholic patients with and without cocaine dependence.
AB  - Neuropsychological functioning of 32 cocaine-dependent, alcoholic patients was
      compared to that of 55 alcoholic patients without cocaine use at the beginning of
      treatment. When the effects of age were statistically controlled, cocaine
      dependent patients performed more poorly on measures of immediate and delayed
      verbal memory. There were no other group differences on screening measures of
      attention, visuoconstructional ability, visuospatial memory, abstract reasoning,
      or practical judgment. Thus, in this sample of alcoholic patients, a specific
      decrement in verbal memory was associated with chronic cocaine use. The brief
      screening battery used in this study might have failed to detect other, more
      subtle impairments in the cocaine-dependent group.

PMID- 14590661
TI  - Cross-validation of predicted Wechsler Memory Scale-Revised scores in a normative
      sample of 25- to 34-year-old patients.
AB  - Equations for prorating Wechsler Memory Scale-Revised General Memory (GM) and
      Delayed Recall (DR) index scores ([Woodard and Axelrod, 1995]) were confirmed in
      the [Mittenberg et al. (1992)] normative WMS-R sample of 50 subjects between the
      ages of 25 and 34, and confirmed in a separate clinical sample of 30 patients
      with closed head injury who were age, education, and gender matched with 30
      subjects from that normative sample. Predicted GM and DR index scores fell within
      6 points of the obtained scores for 98% of the [Mittenberg et al. (1992)] sample
      and 93% to 100% of the matched head injury and normative samples, despite
      statistically significant differences between these groups in obtained GM, DR,
      and percent retention of LM I and II and VR I and II. Six points is well within
      the standard error of measurement of these index scores. These findings confirm
      the earlier cross-validation results reported by [Axelrod et al. (1996)] in a
      mixed sample of traumatic brain injury and other neurological insult, and suggest
      that this method of estimating weighted score sums for WMS-R General Memory and
      Delayed Recall indices may be safely used in normative samples of patients in
      this age range as well as neurologically compromised patients without
      significantly impacting index score accuracy.

PMID- 14590662
TI  - Exploratory factor analysis of the Wechsler Adult Intelligence Scale-Revised in a
      sample of brain-damaged women.
AB  - The first exploratory factor analysis of the WAIS-R using an exclusively female
      sample (N = 152) of brain-damaged patients was conducted. Means for age,
      education, and Full Scale IQ were 43.51 years(SD = 18.22), 12.60 years(SD =
      2.47), and 86.34(SD = 13.32). Results indicated that either a two- or three
      factor model was plausible for this sample. The two-factor solution supported
      Wechsler's (1981) Verbal and Performance IQ designations, while the three-factor
      model revealed Verbal-Comprehension (i.e., Information, Comprehension,
      Vocabulary, and Similarities), Perceptual-Organization (i.e., all Performance
      subtests), and Freedom From Distractibility (i.e., Digit Span) factors.
      Comparison of the factor structures for the present sample with those of normal
      women and brain-damaged men suggested factorial equivalency across groups.

PMID- 14590663
TI  - Employment following severe traumatic brain injury: the utility of the Individual
      Ability Profile system (IAP).
AB  - The results of a survey of employment outcome and their relationship to
      psychometric indices indicated that competitive employment following severe
      traumatic brain injury is an ambitious endeavor. While 98% of the subjects
      sampled were either employed or in school premorbidly, 43% of the subjects were
      unemployed postinjury. Specifically, the Individual Ability Profile (IAP) ([Dean,
      1982][Dean, 1983]) variables developed to assist in the clinical interpretation
      of the results of the WAIS-R were most highly related to employment outcome. A
      discriminant function analysis utilizing these variables yielded hit rates of 82%
      for the unemployed category and 92% for the full-time employment grouping. These
      results further highlighted the useful role of neuropsychological testing in
      assisting in vocational rehabilitation planning. Future research is required to
      further elucidate those neuropsychological abilities that subsequently affect
      employability following severe traumatic brain injury.

PMID- 14590664
TI  - Preparing neuropsychologists for the future: The need for additional training
      guidelines.
AB  - New guidelines for training in neuropsychology are needed for several reasons:
      increased diagnostic accuracy of neuroradiologic techniques: an increasing need
      for functional neuropsychological evaluations; emergence of other psychological
      specialties; and managed care/economic factors. Current INS-Division 40
      guidelines emphasize neurological and diagnostic areas with minimal suggestions
      for training in rehabilitation and functional issues. The recent publication of
      training guidelines for Rehabilitation Psychology (APA Division 22) illustrates
      weaknesses in Division 40 training. It is proposed that neuropsychological
      training guidelines (formal guidelines and informal training experiences)
      incorporate another content area for training and demonstration of competency,
      defined as Functional Outcomes. Specific training is suggested in: (a) issues in
      disability; (b) ecological validity of tests; (c) vocational evaluation/training;
      (d) academic programs for students with disabilities; (e) independent living
      resources; (f) specific cognitive-behavioral interventions; (g) resources for
      individuals with disabilities; and (h) government assistance programs for
      individuals with disabilities.

PMID- 14590665
TI  - Neuropsychological correlates of Gulf War syndrome.
AB  - As part of a comprehensive multispecialty project, the present study reports on
      the neurocognitive and psychological function of veterans who report Persian Gulf
      War-related symptoms. The neuropsychological and psychological performances of 26
      ill Gulf War veterans were compared to 20 well veterans from the same military
      unit. Neurocognitive functions assessed included intelligence, abstraction and
      problem-solving, attention and concentration, memory and learning, language and
      visual-spatial function, and sensorimotor abilities. Psychological function was
      measured by self-report questionnaires. Results indicated global and consistently
      poorer intellectual and neurocognitive function among the ill veterans compared
      to the control veterans. A generalized pattern of neuropsychological deficit was
      evident for the ill veterans. Psychological profiles of the ill veterans were
      similar to those in general medical patients. Based on these findings and results
      from the multispecialty investigation, we conclude that some of the ill veterans
      have experienced neurotoxic injury resulting in chronic neuropsychological
      impairment that is related to their service in the Persian Gulf War.

PMID- 14590666
TI  - Neuropsychological assessment of relatively intact individuals: pychometric
      lessons from an HIV+ sample.
AB  - The assessment of relatively intact individuals poses special problems for
      neuropsychologists, because fine discriminations are often needed to identify
      subtle deficits or gradual declines in performance. Many neuropsychological
      tests, however, are not well-suited for making such exact discriminations. 117
      HIV+ individuals were administered 26 different neuropsychological tests that
      produce 48 scores. Measures of skewness and kurtosis were used to identify
      nonnormal sampling distributions. While many tests showed good sampling
      distributions, several demonstrated ceiling effects and other restrictions of
      range. This included some tests, such as Boston Naming and Lafayette Grooved
      Pegboard, that are not ordinarily considered screening instruments. Such
      nonnormal distributions distort the interpretation of clinical and research data,
      and indicate a need to use tests that are suited to the abilities of the
      population being assessed.

PMID- 14590667
TI  - Longitudinal analysis of olfactory deficits in HIV infection.
AB  - The presence and degree of odor identification deficits in 55 HIV-infected (30
      asymptomatic, 25 symptomatic) and 29 HIV-negative at-risk control volunteers were
      examined longitudinally using the University of Pennsylvania Smell Identification
      Test (UPSIT). Factors other than HIV infection that could account for olfactory
      loss (i.e., sinusitis or upper respiratory infection) were also considered by
      obtaining MRI scans of the nasal passages and information from an olfaction
      questionnaire. No differences were found among groups at the first administration
      of the UPSIT, with significant differences among groups emerging at the 1-year
      and 2-year follow-ups. The symptomatic group showed a significant decline in odor
      identification scores across time, while means for the asymptomatic and control
      groups remained stable. The presence of sinusitis or an upper respiratory
      infection appeared to have no effect on odor identification. The implications for
      these findings in relationship to cognitive decline in neurodegenerative diseases
      are discussed.

PMID- 14590668
TI  - Self-reported levels of anxiety do not predict neuropsychological performance in
      healthy men.
AB  - It is widely believed that even mild to moderately severe levels of anxiety have
      a negative impact on neuropsychological performance. To test that possibility, we
      used scores from Spielberger's State and Trait Anxiety scales to predict
      performance on measures of attention, learning, memory, mental flexibility, and
      eye-hand coordination. Two samples of healthy young and middle-aged men were
      studied. Sample 1 consisted of 125 university students (M age = 20.37); Sample 2
      consisted of 50 men recruited from the community (M age = 40.64). Results of
      multiple regression analyses revealed no significant associations in either
      sample, after controlling for age, education, and average alcohol consumption.
      These findings suggest an absence of relationship between self-reported symptoms
      of anxiety and neuropsychological function in healthy men.

PMID- 14590669
TI  - Learning and memory in adolescent psychiatric inpatients with major depression: a
      normative study of the California Verbal Learning Test.
AB  - Depressed adults have deficits in memory functions, especially on demanding
      tasks, but few studies of depressed adolescents have been published. In order to
      examine the extent of memory impairment and its diagnostic specificity,
      adolescent inpatients with DSM-III-R diagnoses of Major Depression (n = 56),
      Conduct Disorder (n = 42), or mixed Depression and Conduct Disorder (n = 22) were
      tested on the California Verbal Learning Test (CVLT) and compared to each other,
      to CVLT norms, and to previously published CVLT norms for adults with Major
      Depression. Adolescents with Major Depression performed below normative standards
      on all aspects of the CVLT, but did not have a specific profile of memory
      impairments that was different from the two comparison samples. Relative to norms
      for adult patients with Major Depression, adolescent females under performed
      across all CVLT measures, but males did not differ from adults Depression in
      adolescence is not associated with specific memory impairments, but adolescent
      females with depression may have more severe deficits than depressed adults.

PMID- 14590670
TI  - Detection of malingering on the Halstead-Reitan Battery: a cross-validation.
AB  - Using the Halstead-Reitan Battery profiles of 796 people, a formula for the
      detection of malingering was cross-validated to assess the false positive rate.
      Subjects included normals, psychiatric cases, and all major types of organics.
      The formula incorrectly designated 27% of the sample as fakers (i.e., as false
      positives). Of the 120 head trauma cases, 27 (22.5%) obtained Fake scores, while
      93 (77.5%) were correctly assessed as not malingering.

PMID- 14590671
TI  - Determining neuropsychological impairment using estimates of premorbid
      intelligence: comparing methods based on level of education versus reading
      scores.
AB  - When inferring brain dysfunction, test scores are typically compared to normative
      data based on estimates of premorbid intelligence (e.g., by educational level or
      reading scores). However, these methods are likely to lead to differing results,
      with important diagnostic and forensic implications. The current study compared
      estimates of impairment (reported in z-scores) based on educational level versus
      reading scores in a population with traumatic brain injury. The study included
      174 patients (M age = 27.3; M education = 12.3) evaluated as outpatients at a
      university hospital rehabilitation department. Wilcoxen ranked sign tests
      indicated that the two methods yielded estimates that were statistically
      different (p <.0001) for all variables. The education based method yielded
      greater estimates of impairment than the reading score method for WAIS-R FIQ.
      Grip Strength, and Finger Tapping, with a pattern of generally consistent
      impairment across cognitive/motor areas (z-score range = -0.59 to -.97). In
      contrast, the reading score based method yielded greater estimates of impairment
      in processing speed (Trails A) and flexibility (Trails B), with a wider range of
      impairment noted between cognitive and motor domains (z-score range = +0.21 to 
      2.95). Clinical implications are discussed.

PMID- 14590674
TI  - Grief reactions of mothers of adolescents and young adults with traumatic brain
      injury.
AB  - One hundred and two mothers of adolescents and young adults with traumatic brain
      injury completed a modified Grief Experience Inventory (GEI) (Sanders, Mauger, &
      Strong, 1985) and rated their child's functioning on a modified Neurobehavioral
      Rating Scale (NRS) (Levin et al., 1987). More severe grief was reported by
      mothers who rated their children as having poor neurobehavioral functioning and
      by mothers of young adult rather than adolescent patients. The guilt component of
      grief varied significantly across the 3-year post-injury period measured in the
      study. Historical comparisons of these respondents with other bereaved
      populations showed that mothers of adolescent and young adults with head injury
      reported more intense grief than parents who had experienced other significant
      non-death losses.

PMID- 14590675
TI  - Eliciting parental report following pediatric traumatic brain injury: preliminary
      findings on the Pediatric Inventory of Neurobehavioral Symptoms.
AB  - The current article presents preliminary normative data for the Pediatric
      Inventory of Neurobehavioral Symptoms (PINS), a parent rating scale consisting of
      symptoms associated with post-traumatic cerebral dysfunction, such as
      disinhibition, perseveration, reduced spontaneity, inappropriate affective
      responses, episodic phenomena, and disruptions of biologic function. Comparison
      data from a sample of 50 elementary age children who had sustained traumatic
      brain injury (TBI) reveals significant differences on the PINS total score and
      each of five subscale scores. Two of the 5 PINS subscales (Episodic Symptoms,
      Biologic Signs) significantly differentiated the TBI and Attention Deficit
      Hyperactivity Disorder (n = 35) groups, suggesting that these may be clinical
      features that distinguish post-traumatic cerebral dysfunction from developmental
      psychopathology. Despite the need for additional research, the PINS appears to be
      a promising new measure in advancing our understanding of the neurobehavioral
      sequelae of pediatric traumatic brain injury.

PMID- 14590676
TI  - Modal profiles for the Halstead-Reitan Neuropsychological Battery for Children.
AB  - Modal Profile Analysis was used to cluster students (aged 9 to 14 years) on 16
      subtest scores from the Halstead-Reitan Neuropsychological Battery for Children
      (HRNB-C). This analysis produced eight modal profile types, all of which were
      replicated in multiple samples. An initial attempt to establish external validity
      indicated that the modal groups display dissimilar patterns of performance on
      independent variables. The present typology is compared to similar typologies
      developed with adult neuropsychological data. In sum, the current classification
      system provided less coverage than the adult typologies, but produced more unique
      or homogeneous modal groups. Discussion focuses on potential clinical and
      research uses of the modal HRNB-C profiles.

PMID- 14590677
TI  - The affective Auditory Verbal Learning Test.
AB  - The study of emotion is hindered by the lack of tests for affect perception or
      comprehension. One solution is to develop affective versions of well-known tests.
      Using an index of word norms (Toglia & Battig, 1978), positively and negatively
      valenced word lists were developed as alternate forms of the affectively neutral
      Auditory Verbal Learning Test (RAVL; Rey, 1964). Participants (N=102) received
      either the original RAVL list, the positively valenced list, or the negatively
      valenced list. Results are depicted across acquisition trials and location within
      the list for comparison of primacy and recency effects. Each word list yielded
      comparable patterns of acquisition. Participants receiving the negative list
      evidenced an enhanced primacy effect, while participants receiving the positive
      list evidenced an enhanced recency effect. The positive and negative lists may
      prove useful in the evaluation of individuals with affective disorders and may
      provide an alternative for affect induction through an active learning paradigm.

PMID- 14590678
TI  - Adaptive and maladaptive utilization of color cues by patients with mild to
      moderate Alzheimer's disease.
AB  - The ability to utilize color information was investigated in 12 patients with
      mild to moderate probable Alzheimer's Disease (DAT) and in 12 age- and gender
      matched control subjects. All subjects underwent testing of visual acuity and
      color vision before being tested with a cognitive task consisting of four
      conditions (no color, color as attention enhancer, color as valid cue, color as
      distracter). Although the groups did not differ in visual acuity or color vision,
      patients with DAT were less accurate than controls in all four conditions of the
      cognitive task. Both groups performed best with color as a valid cue and worst
      with color as distracter, but condition had a significantly stronger effect on
      patients than on controls. It is concluded that color is a potent stimulus
      attribute for patients with DAT.

PMID- 14590679
TI  - Ability of the Cognitive Behavioral Driver's Inventory to distinguish malingerers
      from brain-damaged subjects.
AB  - The Cognitive Behavioral Driver's Inventory (CBDI) was analyzed for its ability
      to discriminate brain-damaged patients from intact subjects who feigned brain
      damage. In a sample of 251 neurologically impaired patients and 48 malingering
      volunteers, the computer-administered distinguished most malingerers from genuine
      patients. A jackknifed count revealed that the CBDI had 90% sensitivity for
      detecting malingerers, and 98% specificity for detecting non-malingering brain
      damaged patients. Success was due to the inability of malingerers to avoid
      quantitative errors: excessive response latencies, unusual error rates, inflated
      variability in response latencies, and excessive within-subject, between-item
      variability. The computer-administered battery may be an effective clinical tool
      for identifying patients who malinger brain-damage in neuropsychological testing.

PMID- 14590680
TI  - Detection of malingering on the Luria-Nebraska Neuropsychological Battery: an
      initial and cross-validation.
AB  - A formula for detecting faked LNNB profiles was validated on 68 experimental
      malingerers and adequately motivated patients matched on education, age, and
      severity of profile. The formula was then cross-validated on 51 malingerers and
      202 patients. The formula yielded a cross-validated 23% false negative rate and a
      9% false positive rate, for an overall hit rate of 88%. If normal and profoundly
      impaired profiles are eliminated from the cross-validation analysis, the false
      negative rate is 17% and the false positive rate 7%, for an overall hit rate of
      91%.

PMID- 14590681
TI  - Performance of substance abusers with memory deficits on measures of malingering.
AB  - The effects of memory impairment on various malingering indices were assessed in
      a substance abusing population. Groups were formed by using scores from the
      Delayed Memory Index of the Wechsler Memory Scale-Revised and selecting
      individuals from an addictions recovery unit in the top and bottom quintiles.
      Quintile group differences were found for number correct on free and forced
      choice recall on the 21-Item Wordlist; total time for grouped and ungrouped dots
      on the Rey Dot Counting procedure; and addition errors on the Memorization of 16
      Items test. All differences found were in the direction of better performance by
      subjects with better Delayed Memory Index scores; however, all of the differences
      were small. With the exception of the free recall index from the 21-Item
      Wordlist, all subjects had scores on the malingering measures beyond the cutoffs
      typically used to detect malingering in clinical populations. These findings
      suggest that, even in memory-impaired populations, memory measures of malingering
      are valid.

PMID- 14590996
TI  - Investigation of possible cognitive, behavioral, and emotional heterogeneity in
      patients with Alzheimer's disease.
AB  - This study sought to examine whether subtypes of patients with Alzheimer's
      Disease (AD) existed as measured by seven scales of the Cognitive Behavior Rating
      Scale (CBRS). Wards' method of cluster analysis was used to group 104 AD patients
      into subgroups. Three clusters were identified: (a) Moderately Impaired, (b)
      Severely Impaired, and (c) Emotionally Intact. These clusters displayed more
      differences in symptom severity than type of symptom. Clusters could be partially
      defined by the amount of time since diagnosis, while differences in the clusters'
      profile of scores had little or no descriptive utility. Results failed to support
      the existence of AD subtypes and yet did not follow the traditional "stage"
      descriptions of AD progression either. Findings are discussed within a modified
      "phase" description of AD progression.

PMID- 14590997
TI  - Assessing believable deficits on measures of attention and information processing
      capacity.
AB  - The vulnerability of tests of sustained attention and speed of processing to
      faked deficits was evaluated by comparing the performances of normal controls,
      healthy subjects asked to simulate deficits, and patients with closed head injury
      on a simple auditory reaction-time task and on the PASAT. The results revealed
      that persons attempting to feign the effects of brain injury perform more poorly
      than non-malingerers on a simple reaction-time task and the PASAT. The reaction
      time task, however, proved more effective than the PASAT at detecting
      dissimulation, accurately classifying about 76% of the subjects. This value
      reflects a respectable hit rate for three-group classification.

PMID- 14590998
TI  - The effects of traumatic brain injuries on information processing.
AB  - Many individuals experience memory impairment subsequent to traumatic brain
      injuries (TBI). These memory deficits may result from general impairment of
      information processing rather than damage to memory critical neurological
      systems. The investigators examined learning time and recall errors for easy and
      hard word pairs in a distraction and no-distraction condition to examine learning
      patterns. Although results indicated that individuals with and without TBI
      generally showed the same learning and retrieval patterns, individuals with TBI
      did so in an accentuated manner. This suggests that attentional deficits
      associated with TBI are not responsible for subsequent memory deficits.

PMID- 14590999
TI  - Neuropsychological assessment and malingering: a critical review of past and
      present strategies.
AB  - In recent years, neuropsychologists and clinical psychologists have shown a
      greatly increased interest in methods of discriminating malingerers from
      legitimate psychiatric and neurological patients. In part, this increased
      interest has resulted from increased demand from the legal system (i.e.,
      pertaining to disposition of personal injury, worker's compensation, medical
      malpractice, and criminal cases) for expert psychological testimony which can
      distinguish malingering from genuine neuropsychological deficits. Additional
      interest, and some controversy, has been generated by recent research studies
      that have reported no success in diagnosing malingering, although others have
      reported more positive evidence. The present literature review describes the
      historical and current methods of detecting malingerers, along with the empirical
      evidence supporting, or condemning, their use. The majority of empirical studies
      suggest that although malingering of brain dysfunction is not easy to detect, it
      is possible to detect, if looked for deliberately. Review and critique of the
      available strategies indicates that a multidimensional, multimethod approach is
      needed. Continued research effort is needed on this important clinical issue.

PMID- 14591127
TI  - Factor analysis of verbal and nonverbal clinical memory tests.
AB  - This study represents an attempt to evaluate the construct validity of various
      verbal and nonverbal clinical memory tests. Marker variables for verbal, visual
      perceptual-motor and attention-concentration abilities were employed in order to
      demonstrate the relative independence of these abilities from the memory
      measures. Subjects were 119 individuals (aged 16-74) from a combined sample of
      brain damaged and non-neurologic medical controls. Principal components analyses
      with orthogonal varimax rotations produced four factors in both Immediate and
      Delayed analyses: nonverbal memory and visual-perceptual-motor skills, verbal
      learning and memory, general verbal abilities, and attention-concentration. The
      inclusion of additional nonverbal memory measures helped to create a modality
      specific nonverbal factor but did not produce a pure nonverbal memory factor. The
      Wechsler Memory Quotient had modest loadings on three of the four factors.

PMID- 14591000
TI  - Comparative three-factor solutions of the WISC-III and WISR-R at 11 age levels
      between 6-1/2 and 16-1/2 years.
AB  - The Wechsler Intelligence Scale for Children, Third Edition (WISC-III) was factor
      analyzed at ages 6 12 through 16 12 years of age (n = 200 per age group). The
      study replicated analyses conducted by Kaufman (1975) with the WISC-R using
      comparable subtests across the two scales. As in the WISC-R study, a three-factor
      structure emerged as consistent across the age range of the WISC-III: Verbal
      Comprehension, Perceptual Organization, and Freedom from Distractibility. The
      results of the study are discussed in terms of their clinical utility with useful
      statistics for the interpretation of the WISC-III presented.

PMID- 14591128
TI  - Hemispheric asymmetry in the processing of tactual-spatial material of low verbal
      codability in normal subjects.
AB  - Two experiments were carried out using a modified Tactual Performance Test (TPT)
      to investigate patterns of tactual-spatial performance and memory in normal
      individuals. Right-handed mates were tested using either a right-left-both hands
      or left-right-both hands order. The left-hand-first group had better tactual
      spatial memory than the right-hand-first group. In a second experiment, right
      handed males performed the TPT with either the left hand or the right hand on all
      trials while simultaneously palpating a non-task-related nonsense figure with the
      opposite hand. The left-hand group had better time scores and memory for TPT
      figures than did the right hand group. The findings, consistent with previous
      studies, indicate a saliency of the right hemisphere in tactual-spatial
      performance and memory and suggest that dichhaptic stimulation may be the
      preferred method for revealing hemispheric asymmetries in tactual-spatial
      functioning.

PMID- 14591129
TI  - Some putative cognitive precursors in subjects hypothesized to be at-risk for
      dementia.
AB  - Virtually no data exists on the early cognitive precursors of dementia, primarily
      SDAT. This paper presents preliminary cross-sectional data on two elderly groups
      hypothesized to be at risk for SDAT and a well group matched individually on age,
      education and gender. The neuropsychological results, based on factor scores and
      individual t-test comparisons, revealed significant differences between the well
      group and the two at risk groups, each of which revealed a different pattern of
      cognitive impairment (specific vs. general). These results stimulated a number of
      hypotheses concerning the early precursors of SDAT that will be tested in the
      annual follow-up investigation of these subjects.

PMID- 14591130
TI  - Systems model of cortical organization: positron emission tomography and
      neuropsychological test performance.
AB  - Positron Emission Tomography (PET) has allowed researchers to examine in vivo
      brain-behavior relationships. Correlations of metabolic increases measured by PET
      with simple sensory tasks involving hearing, vision, and tactile/motor responses
      have generally produced metabolic changes in agreement with known neuronal
      pathways. However, complex neuropsychological tests such as Raven's Matrices and
      Verbal Fluency have resulted in cortical activation of unexpected areas as well
      as some negative correlations between test performance and metabolism. These
      observations provide the first demonstration of complex relationships between
      neuropsychological functioning and activation of the normal brain. Since PET
      technology offers a means of computing the simultaneous proportional contribution
      of multiple brain regions, the issue of "localization" of neuropsychological test
      performance might appropriately be considered for redefinition in terms of a
      "systems" approach. In spite of the advances brought about by PET, methodological
      problems still remain for researchers. Future studies will need to take into
      account the subtle regional effects of neuropsychological paradigms.

PMID- 14591131
TI  - Relative influence of subject variables and neurological parameters on
      neuropsychological performance of adult seizure patients.
AB  - We present the results of a study examining relationships between subject
      characteristics (age, education, sex, race) and neurological factors on
      neuropsychological test performance of adult seizure patients. Test scores from a
      modified and expanded Halstead-Reitan test battery for 250 epileptics served as
      criterion variables for sets of multiple regression analyses using subject
      characteristics and neurological parameters as predictors. Initially, subjects
      were divided into two subsamples and separate analyses for subject and
      neurological variables were pursued. Double cross-validated results indicated
      that test performance was significantly related to both sets of predictor
      variables, yet the magnitudes of relationship were rather consistently highest
      for demographic attributes. The relative contribution of individual predictor
      variables subsequently was explored in a second set of multiple regression
      analyses examining both subject and neurological variables within the combined
      patient sample. Results indicated that one or more subject characteristic plus
      one or more neurological variable accounted for a significant amount of test
      variance for almost all of the measures under consideration. A subject variable
      was entered first in step-wise regression analyses for 78 % of the measures, with
      education proving to be the most potent predictor of test status. In general,
      these data support the need for test norms which make adjustments for
      nonneurological subject attributes.

PMID- 14591132
TI  - The relationship between neuropsychological impairment in alcoholics and
      treatment outcome at one year.
AB  - One hundred and thirty-two (132) patients with a diagnosis of alcohol dependence
      who participated in an inpatient treatment program were assessed on select
      neuropsychological measures and followed for a one year period.
      Neuropsychological, personality, and demographic variables did not predict
      outcome defined as abstinence at one year follow-up. Relapsed patients displayed
      slightly better initial neuropsychological functioning compared to abstainers,
      although this effect was not significant when these measures were controlled for
      age and education. These findings and the clinical implications of
      neuropsychological assessment in alcoholic populations is discussed.

PMID- 14591133
TI  - Neuropsychological and behavioral sequelae of amitriptyline overdose in infancy.
AB  - This study reports on the neuropsychological and behavioral problems of a 3(1/2)
      year-old boy who was poisoned by his Nanny with a massive dose of amitriptyline
      hydrochloride subsequent to a period of supranormal development. At the age of 8
      months, the child was discovered at home in respiratory distress (he was "blue
      and not breathing"). Blood gases and toxin screens revealed a serum level of 1065
      ng/ml for amitriptyline. The parents have reported a series of serious behavioral
      and emotional problems since this incident. Neuropsychological data gathered
      recently at the age of 3(1/2) years indicated a variety of nonfocal signs.
      Language development, serial processing skills, and attentional mechanisms showed
      the greatest degree of impairment.

PMID- 14591134
TI  - Equivalence of items on the mini-mental state.
AB  - Procedural variations affecting the reliability of the Mini-Mental State (MMS)
      were investigated in three studies using three different populations. Consistent
      results were obtained from studies of neurologically normal, at-risk, and
      impaired individuals which show that the test item involving serial subtractions
      is significantly more difficult than the alternative item involving backward
      spelling. MMS users are cautioned against assuming the comparability of scores
      across individuals, and should specify which attention and concentration task
      they employ in their evaluations.

PMID- 14591135
TI  - A note regarding some aspects of the history of clinical neuropsychology.

PMID- 14591136
TI  - An analysis of the significance of performance errors on the Trail Making Test in
      polysubstance users.
AB  - The Trail Making Test performance of a group of polysubstance users was evaluated
      in order to analyze the stability of performance errors between two
      administrations. Two categories of errors were identified: sequential (Part A)
      and sequential and/or perseverative (Part B). The general findings revealed
      statistically significant test-retest effects. The utility of performance errors
      as indicators of stable CNS dysfunction is discussed in view of these findings.

PMID- 14591138
TI  - Archives of Clinical Neuropsychology. Editor's note.

PMID- 14591139
TI  - Neuropsychological test performance among major clinical subtypes of depression.
AB  - Thirty-six patients with diagnoses of major depression were administered the
      Luria-Nebraska Neuropsychological Battery. Comparisons were made on six
      dichotomous subtypes of depression: agitated-nonagitated, endogenous
      nonendogenous, primary-secondary, psychotic-nonpsychotic, retarded-nonretarded,
      and unipolar-bipolar. The psychotic depressives were more impaired than the
      nonpsychotics on the Profile Elevation and Impairment scales. No differences were
      found for other subtype comparisons on these global measures of
      neuropsychological dysfunction. Analysis of age effects indicated that older
      depressives performed more slowly on timed performance items and significant
      subtype differences on these items occurred for subtype diagnoses of psychotic,
      primary, and retarded depression. Localization and Lateralization scales revealed
      significant impairment for the psychotic and retarded patients, with less
      impairment for other subtypes. The relevance of these findings for
      neuropsychological evaluation are discussed, particularly with regard to the
      potentially confounding effects of depression on test performance.

PMID- 14591140
TI  - Lateralization of visual hemifield attention across development.
AB  - Heilman and Valenstein (Clinical Neuropsychology, 1979, Oxford University Press,
      New York) have hypothesized a right hemispheric mechanism which mediates
      attention bilaterally. Shapiro and Hynd ("The development of functional
      lateralization in visual hemifield attention." Developmental Neuropsychology,
      Vol. 1, pp 67-80, 1985) examined the developmental validity of this model and
      their findings did not provide evidence for a lateralized mechanism for visual
      hemifield attention in 9, 13, and 18 year olds. However, length of foreperiod and
      gender effects were noted. This study attempted to compare these groups with a
      group of normal adults (ages 25-35) using the same reaction time paradigm. The
      study demonstrated support for the length of foreperiod effect found by Shapiro
      and Hynd. Hand effects were also found. However, these results do not lend
      support to either the model proposed by Heilman and Valenstein (1979) or Shapiro
      and Hynd's (1985) notion of developmental differences across age groups with
      respect to right hemisphere dominance for mediating attention.

PMID- 14591141
TI  - Progression of neuropsychological deficits following toluene diisocyanate
      exposure.
AB  - Three wharf workers were acutely exposed to toluene diisocyanate (TDI) during an
      accidental chemical spill. Toluene is neurotoxic as a solvent, while cyanates can
      cause nervous tissue injury or death by hypoxia. Chronic symptoms which occurred
      following the incident included headache, fatigue, concentration problems,
      irritability, depression, sleep disturbance, memory and sexual dysfunction.
      Compared with two months post-exposure, at 16 months post-exposure Full Scale IQ
      dropped an average of 23 points. Results from additional neuropsychological
      testing at 16 months post-exposure indicated severe deficits in all three
      subjects in memory, manual dexterity, visuomotor tracking, mental flexibility,
      ability to detect figure-ground relationships, and word fluency. Nerve conduction
      velocity testing indicated abnormal peripheral nervous system function in two of
      the three workers; however, its etiology is not certain. These results may be
      relevant to the neurotoxicity of methyl isocyanate exposure, such as occurred in
      Bhopal, India, where an increasing magnitude of depression, anxiety, fatigue,
      restlessness, and headaches 18 months post-exposure have been reported. In
      general, continuing decrement in mental function without concomitant
      environmental exposure should be considered in neuropsychological assessment of
      chemical toxicity.

PMID- 14591142
TI  - The use of neuropsychological evaluation in the medical management of subdural
      empyema.
AB  - Subdural empyema is in itself an uncommon complication of infection in childhood
      and localization of the infection to the parafalcine area is rare. This paper
      presents a case study of a teenager with subdural empyema resulting from
      paranasal sinusitis, who presented as a parafalcine syndrome and was treated
      successfully without neurosurgical intervention. Results of repeat
      neuropsychological evaluation (premorbid, 17 days into treatment, and after six
      months), correlated with changes seen on serial CT scanning during treatment and
      follow up. More importantly, the neuropsychological evaluation was clinically
      more sensitive than the traditional neurological examination in assessing changes
      in cortical integrity during the course of recovery. Thus, neuropsychological
      evaluation proved to be a valuable supplement to the neurological examination in
      exploring morbidity and assisting in treatment decision making in the management
      of subdural empyema.

PMID- 14591143
TI  - An experimental evaluation of the efficacy of suloctidil in the treatment of
      primary degenerative dementia.
AB  - A double-blind, placebo-controlled randomized design was employed to test the
      efficacy and optimal dosage of Suloctidil in the treatment of primary
      degenerative dementia (PDD i.e., Alzheimer's disease). Initially, 30 geriatric
      patients with a diagnosis of PDD were matched for age, education, and handedness,
      and randomly assigned to one of three groups: (a) 600 mg. Suloctidil daily; (b)
      450 mg. Suloctidil daily; (c) or placebo, for 12 weeks. All patients were
      administered individually a brief neuropsychological battery at pretreatment and
      at 12-week posttreatment. The tests were the Boston Naming Test, the Thurstone
      Word Fluency Test, the Trail Making Test, and the Grooved Pegboard. While there
      was differential attrition across the three groups, the results of the Boston
      Naming Test suggest a medication-dosage effect.

PMID- 14591144
TI  - The neuropsychological approach to the remediation of dyslexia.
AB  - The neuropsychological approach to remediation emphasizes the use of intact areas
      of higher cortical functioning in the development of remedial strategies while
      minimizing the emphasis placed upon dysfunctional cortical areas. This
      investigation was directed towards evaluating the effectiveness of the
      neuropsychological approach to the remediation of developmental dyslexia in
      school age children previously placed in self-contained classrooms for the
      learning disabled due to reading failure. A significant improvement in word
      recognition skills was demonstrated with a similar, but nonsignificant, trend
      noted in reading comprehension.

PMID- 14591145
TI  - Grand Rounds.

PMID- 14591146
TI  - The clinical significance of cerebral atrophy in dementia.
AB  - The clinical significance of cortical atrophy is reviewed in relationship to
      neuropsychological impairment in dementia of the Alzheimer type. The degree of
      cortical atrophy may vary independent of the degree of cognitive impairment.
      There is some tendency for greater amounts of cortical atrophy to be associated
      with greater cognitive deficits, but individual variations limit the linearity of
      this relationship. On an individual case basis, lateralized atrophy in some
      patients may be associated with greater lateralization of cognitive impairment.
      Cortical atrophy patterns do not differ substantially in the pre-senile and
      senile forms of Alzheimer's disease. Neuropsychological follow-up provides a
      better index of the speed of deterioration in Alzheimer's disease than does
      computerized tomography (CT) or magnetic resonance imaging (MRI). Various
      clinical guidelines are offered for the interpretation of neuropsychological
      impairment based upon CT or MRI findings of cerebral atrophy.

PMID- 14591148
TI  - Differential sensitivity of the WAIS and a modified Halstead-Reitan battery to
      severity of brain dysfunction in epilepsy.
AB  - The present study examined the diagnostic sensitivity of the WAIS relative to a
      modified Halstead-Reitan test battery by comparing the accuracy of these
      instruments in differentiating pseudoneurologic control subjects from two groups
      of epileptics which were believed to differ in degree of underlying brain
      pathology. A total of 96 subjects were equally represented in the control, mildly
      impaired, and moderately impaired study groups. Separate three-group and two
      group discriminant function analyses were performed for the two sets of measures.
      Comparisons of kappa coefficients indicated that the WAIS was inferior in
      classification accuracy to the neuropsychological tests in making the three-group
      discriminations and in separating the mildly impaired subjects from the
      moderately impaired group. These findings suggest that the WAIS may be inferior
      in discriminatory power relative to a wider array of neuropsychological measures
      than has heretofore been evaluated. Furthermore, these data imply that the degree
      of underlying brain involvement associated with a seizure disorder may be
      determined best from neuropsychological tests rather than from a general measure
      of intellectual ability, such as the WAIS.

PMID- 14591149
TI  - Validity and diagnostic accuracy of an alternate form of the Rey Auditory Verbal
      Learning Test.
AB  - The diagnostic validity of an alternate form of the Rey Auditory Verbal Learning
      Test (AVLT) is investigated. Subjects were 73 inpatients from a VA Medical Center
      who were classified as having either intact (n = 41) or impaired (n = 32) memory
      functions. Employing a counterbalanced design, both groups were administered the
      standard (Form A) and alternate (Form C) forms of the AVLT. Means for the
      learning trials, trial VI and the recognition procedure were calculated for the
      intact and memory-impaired subjects and contrasted for each test. Results
      suggested that Form C discriminated groups at a level comparable to that of Form
      A. This impression was confirmed by separate stepwise discriminant analyses for
      Form A and Form C that yielded identical hit-rates (i.e., 75.3%) in terms of
      identifying subjects as memory-intact or memory-impaired. These findings
      suggested that Form C may be used for the assessment of persons with verbal
      mnemonic deficits with the same degree of confidence that has been attributed to
      Form A.

PMID- 14591150
TI  - Neuropsychological characteristics and atrophic brain changes in senile and
      presenile dementia.
AB  - Groups of presenile (n = 41) and senile (n = 97) dementia patients were compared
      on neuropsychological measures and volumetric estimates of atrophy and
      ventricular enlargement as depicted on computerized axial tomography. Despite
      their significantly greater age, the senile patients were not markedly
      significant different on neuropsychological measures when the effect of education
      was covaried. Likewise, there were no significant differences between the two
      groups in terms of cortical atrophy despite that variable's known relationship
      with age. Ventricular size was not significantly different between groups when
      age effects were statistically controlled. It is concluded that the pathologic
      effects of presenile dementia are roughly equivalent to the total of the effects
      of both the disease and aging processes in senile dementia. Therefore, the
      disease appears to be more dramatic when it occurs in younger patients. It may be
      that younger patients are less healthy than older patients presenting with the
      disease and, consequently, are less able to withstand its effects. The present
      sample is compared with those of other studies reporting a markedly more
      pathologic presentation associated with presenile relative to senile dementia.

PMID- 14591151
TI  - The relationship between experimental and neuropsychological measures of memory.
AB  - The current investigation sought to provide convergent and divergent validational
      information on both experimental and neuropsychological measures short versus
      long-term memory. Forty undergraduates (20 male, 20 female) were administered
      memory assessments from the Halstead-Reitan Neuropsychological Battery, the Luria
      Nebraska Neuropsychological Test Battery, and the experimentally developed Paired
      Associates (Face-Name Association & Distractor tasks). Results indicated that the
      experimental measures of memory demonstrated a high degree of convergent and
      divergent validity. Both the Luria-Nebraska Memory Scale and the Halstead-Reitan
      correlated to long-term measures of memory. The Luria Memory Scale did not
      significantly correlate to short-term measures of memory. Selected subtests from
      the Halstead-Reitan correlated to experimentally-derived measures of short-term
      memory. Implications of this study are discussed and recommendations for future
      research is discussed.

PMID- 14591152
TI  - Development and cross-validation of a short form impairment index.
AB  - The Brain Age Quotient (BAQ) is an actuarial combination of four Halstead-Reitan
      neuropsychology test battery scores (Category errors. Tactual Performance Test-
      Total Time, Tactual Performance Test-Location Score and Trails-B Score) and two
      performance subtests for the Wechsler Adult Intelligence Scale (Block Design and
      Digit Symbol). The present studies investigated the value of a short form of the
      BAQ, the Short Form Impairment Index (SFII), composed of the Trails-B Score and
      two subtests of the Wechsler and also twice cross-validated the short form.
      Statistical analysis yielded a Pearson r =.90, for both the initial study and
      each of the cross-validations. Further research and clinical considerations are
      discussed.

PMID- 14591254
TI  - Postconcussion symptoms and daily stress in normal and head-injured college
      populations.
AB  - The postconcussion syndrome is a term invoked to describe a constellation of
      cognitive (decreased memory and concentration), emotional (increased irritability
      and nervousness or anxiety), and physical (increased headaches and dizziness)
      changes that are commonly reported following minor or severe head injuries. The
      first section presents the development and validation of the Postconcussion
      Syndrome Checklist. The second section describes the daily changes in symptom
      reports as a function of daily stress levels. A population of head-injured
      subjects and controls monitored postconcussion symptoms and stress across a 6
      week period. The frequency, intensity, and duration of symptoms reported were
      correlated with daily stress levels as measured by the Daily Stress Inventory for
      both groups. Yet, the number of symptoms reported by our head-injured group did
      not vary significantly from the normal subjects. The data support models which
      predict that postconcussion syndrome varies with stress, but the evidence for a
      reduction in the cerebral reserve capacity after head injury was not supported
      with this population. Explanations for this finding are presented and
      implications of this research and directions for future research are outlined.

PMID- 14591255
TI  - Ipsilesional disruptions to reciprocal finger tapping.
AB  - Impairments in repetitive finger tapping have not been found in the ipsilesional
      hand, possibly because the performance measure (tapping rate) which has been used
      is not sufficiently sensitive. In this study, tapping performance of patients
      with lateralized brain damage was examined using more detailed measures
      reflecting intertap variability and the relative timing of each tap cycle. In
      concert with previous findings, neither the left- nor the right-hemisphere
      damaged patients exhibited an impairment in tapping rate. An impairment in
      tapping variability was observed, however, but only for the left hemisphere
      group. It is argued that intertap variability may be particularly sensitive to
      left hemisphere damage as this measure reflects the demands for rather precise
      and consistent phasing or sequencing of muscle activation. Since left hemisphere
      damage often leads to deficits in making transitions between movements in a
      sequence, the consistent sequencing of agonist-antagonist muscle activations in
      tapping may be compromised. Future research directions to examine this hypothesis
      are discussed.

PMID- 14591256
TI  - Multiple equivalent test forms in a computerized, everyday memory battery.
AB  - Eight parallel forms for six computerized, everyday memory tests were examined
      for equivalence of difficulty level. Six equivalent forms were found for
      Telephone Dialing, Name-Face Association, First-Last Name memory, and Grocery
      List Learning, white eight equivalent forms were found for Misplaced Objects and
      Recognition of Faces. The clinical and research utility of multiple equivalent
      forms of everyday memory tests is discussed.

PMID- 14591257
TI  - A comparison of the matching of emotional information by depressive and organic
      patients.
AB  - The ability to match complex emotional stimuli was assessed in depressed and
      organic neuropsychiatric patients. Subjects were 13 nonorganic-depressed, 13
      organic-depressed, 10 organic-nondepressed, and 10 nonorganic-nondepressed right
      handed adults. They were required to match pictures, sentences, and faces on the
      basis of emotional content in order to determine whether depression resulted in
      difficulties in analyzing emotional information consistent with those seen in
      organic patients. Depression produced an error pattern for the matching of
      complex emotional information that was suggestive of right hemisphere
      dysfunction. It was unclear if this was due to emotional processing defects or a
      more generalized deficit in conceptual processes.

PMID- 14591258
TI  - Hooper Visual Organization Test performance in lateralized brain injury.
AB  - The Hooper Visual Organization Test (VOT) is frequently used in measuring the
      cognitive functioning of brain-damaged patients. It is not clear, however,
      whether the VOT measures general or specific neurological dysfunction,
      specifically those resulting from right parietal lesions. The present study
      addressed this issue by examining archival data from 41 brain-damaged patients
      who were seen in a medical hospital's acute rehabilitation unit. Patients were
      selected on the basis of a diagnosis of either right or left hemisphere damage,
      and VOT scores on these two patient groups were compared. Additionally, lesion
      site, as measured primarily by CT scan, was compared with VOT scores. No
      significant hemispheric differences were found on VOT scores. However, VOT
      scores, when adjusted for age and education, were significantly lower in patients
      with lesions involving the right parietal lobe. The implications of the findings
      for the use of the VOT with brain-damaged individuals are discussed.

PMID- 14591259
TI  - Revised norms and decision rules for the Luria-Nebraska Neuropsychological
      Battery, Form II.
AB  - All control subjects from a previous Luria-Nebraska Neuropsychological Battery,
      Form II (LNNB2) normative study were combined with a considerably larger
      normative sample to produce a composite normative sample of 392 subjects with a
      mean high school educational level. Revised norms for the LNNB2 were developed
      based on this sample and were scaled with uniform T-scores to make scale
      elevations comparable across LNNB2 measures. Differences between the scalewise
      LNNB2 normative values and published alternatives were highly significant. A
      critical level and actuarial decision rules for differentiation of normal from
      neurologically impaired performance level were developed for the LNNB2 using the
      current empirical norms (86% accuracy with current sample empirical critical
      level; 89% accuracy with LNNB1 critical level). The normative prediction values
      of Golden, Purisch, and Hammeke for the LNNB2 were not satisfactory (69% overall,
      with 45% accuracy among brain damaged sample). There was no significant effect of
      sex of subject on LNNB2 performance level among the control subjects.

PMID- 14591260
TI  - Replication of a three-component solution for common measures of attention in HIV
      seropositive males.

PMID- 14591261
TI  - Magnetic resonance identified ventricular dilation in traumatic brain injury:
      comparison of pre- and postin jury scan and postin jury results.
AB  - A case study is presented in which a patient received magnetic resonance (MR)
      imaging of the brain 3 months prior to a severe traumatic brain injury (TBI). The
      post-TBI MR findings are compared and contrasted with the pre-TBI MR images. The
      posttraumatic changes demonstrate a significant dilation of the ventricular
      system which reflects diffuse axonal injury and loss of brain substance.
      Correspondingly, the neuropsychological studies in this individual reflect global
      deficits which match the nonspecific, traumatically induced degenerative changes
      found in the postinjury MR scan. This case study is unique in that specific
      preinjury MR findings are available for direct comparison and quantitative
      analysis of TBI-associated changes in brain structure with neuropsychological
      outcome.

PMID- 14591262
TI  - Functional irregularities of short-term and long-term memory storage in patients
      with Parkinson's disease and Huntington's disease.
AB  - Memory performance of Parkinson's disease patients (PD patients). Huntington's
      disease patients (HD patients) and healthy subjects were compared by a single
      trial free recall task following the presentation of a stimulus list consisting
      of 30 nouns. The patient groups were categorized according to the severity of the
      disease into mild, moderate, and severe. Healthy subjects reproduced
      significantly more words than PD and HD patients, while the two patient groups
      did not differ in the total number of words reproduced. The differences between
      healthy and demented subjects are attributed to the impaired functional capacity
      of long-term memory; there were significant differences between healthy subjects
      and patients as well as between PD and HD patients. When taking the severity of
      the disease into consideration, varied influence on the capacity of long-term
      memory for PD and HD patients was found. Concerning short-term memory, neither a
      difference between healthy subjects and patients nor between both patient groups
      could be established. An effect of the severity of the disease could not be
      proven.

PMID- 14591263
TI  - Individual differences in the cerebral organization of language using input and
      output interference measures of lateralization.
AB  - The literature on the relationship between cerebral lateralisation and the
      combined effects of sex and handedness, reveals many discrepant findings. In an
      effort to clarify these discrepancies, three different types of interference
      cerebral lateralization tasks were used in a relatively large sample of normal
      individuals. Handedness differences were found in the expected direction on all
      three lateralization measures: input interference (dichotic listening), and two
      output interference measures, a motor-motor interference task (concurrent finger
      tapping and verbal fluency) and a motor-cognitive interference task (concurrent
      finger tapping and silent reading). A sex difference, however, was found on only
      the motor-motor interference task. These results suggest that possible sex
      differences in cerebral lateralisation may be less prominent among particular
      types of interference laterality tasks, and more reliably found with motor-motor
      interference lateralization measures.

PMID- 14591264
TI  - Intercorrelation of clinical tests of verbal memory.
AB  - The Wechsler Memory Scale, Buschke Selective Reminding Test, and Rey Auditory
      Verbal Learning Test were administered to 25 patients with known or suspected
      cerebral dysfunction. Intercorrelation of subscales revealed generally modest
      relationships among measures, indicating that there may be considerable
      variability in an individual's performance across the three tasks. This finding
      has significant clinical and research implications.

PMID- 14591265
TI  - Personality/behavioral characteristics in children: differential effects of
      putative anterior versus posterior cerebral asymmetry.
AB  - The current study was carried out to examine the possible relationships among
      personality/behavioral characteristics and anterior/posterior (A/P) functional
      cerebral asymmetry in children referred for learning problems. Two hundred
      nineteen children between 7 and 12 years of age were administered a battery of
      neuropsychological measures, and their parents completed the Child Behavior
      Checklist (CBC) and the Personality Inventory for Children-Revised (PIC).
      Anterior and posterior composite scores were obtained for each subject using
      scores on the neuropsychological measures. Out of this subject pool, 33 children
      had sufficient anterior/posterior (A/P) score differences (i.e., greater than one
      standard deviation difference) to permit their categorization into either an A (n
      = 19) or P (n = 14) group. The MANOVA results showed that the A group scored
      significantly higher than the P group on the CBC scales of social withdrawal,
      aggressiveness, hyperactivity and externalizing, while the P group scored higher,
      though not significantly, on the (PIC) scale of anxiety. Thus, it appeared that,
      by using neuropsychological measures along the A/P dimension to classify children
      with learning problems, significant differences could also be identified on
      personality/ behavioral variables for some children. In addition, in the current
      study, children with A type functional cerebral asymmetry exhibited a relatively
      greater number of behavioral problems.

PMID- 14591266
TI  - Laterality of brain damage and emotional disturbance in adults.
AB  - Although there has been agreement that brain injury often alters emotional
      functioning, there has been little agreement regarding the effects of lateralized
      brain injury on emotional status. The current study examined a fairly large
      sample of lateralized brain injured patients (N = 186) and compared scores on an
      objective self-report measure of personality or emotional status (MMPI). Results
      are consistent with prior studies by Reitan and others in that there were no
      significant differences between lateralized groups. Both groups showed moderate
      elevations (T scores in the low 60s) on scales 1, 2, 3, and 8. This was
      interpreted as reflecting somatic concern, mild-moderate depression, and
      interpersonal difficulties.

PMID- 14591267
TI  - Neuropsychologists' training, experience, and judgment accuracy.
AB  - It is often assumed that judgment accuracy improves as clinical training and
      experience increase, but the few studies on this topic within neuropsychology
      have yielded negative findings. In an extension of prior research, we obtained
      information on background training and experience from a nationally
      representative sample of clinical neuropsychologists and had each practitioner
      appraise one from among a series of 10 cases. Except for a possible tendency
      among more experienced practitioners to overdiagnose abnormality, no systematic
      relations were obtained between training, experience, and accuracy across a
      series of neuropsychologic judgments. Comparable results were obtained when
      analysis was limited to the top versus bottom 20% of the sample. This and other
      studies raise doubt that clinical neuropsychologists train and practice under
      conditions conducive to experiential learning. The potential benefits of further
      research on experience and judgment accuracy are discussed.

PMID- 14591268
TI  - The efficacy of structured memory retraining in a group comparison of head trauma
      patients.
AB  - Empirically proven mnemonic techniques from the literature were assembled into a
      comprehensive treatment program for brain injured clients. Twenty head injured
      subjects with mild to moderate neuropsychological impairments were matched on the
      variables of age, sex, years of formal premorbid education, and elapsed time
      since insult. These patients were then randomly assigned to either the control or
      experimental remediation group. Both groups attended a six-week program and were
      blind as to what type of treatment they were receiving. Each followed identical
      daily schedules where the experimental group received the formal memory
      remediation and the controls received treatment focusing on psychosocial issues.
      Both groups improved on the neuropsychological memory measures over the course of
      the study. The experimental group did not improve significantly more than did the
      control group; however, once the groups were subdivided according to the severity
      of neuropsychological functioning at intake, significant treatment effects were
      observed. More specifically, only those patients with mild residual impairments
      seemed to benefit from rehabilitative efforts, and those with more moderate
      deficits did not respond to treatment. Clinical implications and future research
      are discussed.

PMID- 14591269
TI  - A comparison of the trail making test, symbol digit modalities test, and the
      Hooper Visual Organization Test in an inpatient substance abuse population.
AB  - Ninety inpatients from a substance abuse treatment facility each completed the
      Symbol Digit Modalities Test, the Trail Making Test and a novel, group
      administered form of the Hooper Visual Organization Test. Patients exhibited
      varying degrees of impairment on all three instruments compared to available
      norms. The correlations among the tests were all statistically significant. The
      lowest inter-test correlations were obtained on the Hooper Visual Organization
      Test. The utility of global neuropsychological screening instruments with
      inpatient substance abusers' is discussed in light of these findings.

PMID- 14591270
TI  - The clinical significance of congenital agenesis of the corpus callosum.
AB  - Three cases of congenital agenesis of the corpus callosum (ACC) are presented
      along with typical clinical features observed on computerized tomography and
      magnetic resonance imaging. Most congenital ACC cases do not display hemi
      syndromes or callosal syndromes, but do exhibit some deficit in terms of
      hemispheric integration. The most common neuropsychological impairments are in
      the areas of motor and perceptual-motor functioning. Clinical guidelines in the
      assessment of ACC patients are given.

PMID- 14591272
TI  - Autonomie responsivity following closed head injury.
AB  - It has recently been suggested that certain posttraumatic head injury patients
      exhibit impaired central nervous system arousal mechanisms, which may underlie or
      contribute to subsequent behavioral and cognitive disturbance. The present study
      examined skin conductance levels and responsivity in a group of 15 patients
      recovering from closed head injuries (CHIs) with 15 matched controls.
      Measurements were taken during rest periods and two activation periods.
      Activation periods consisted of 1) a series of 80 dB tones; and 2) a cognitive
      task (Symbol Digit Modalities Test). Patients exhibited significantly lower
      levels of skin conductance and significantly fewer responses than the control
      group. Group by task interactions were also significant, indicating that the
      control group was much more responsive during both activation periods. Skin
      conductance responsivity in the patient group was not found to be associated with
      duration of posttraumatic amnesia, behavioral disturbance, or attentional
      functioning, suggesting that the relationship between decreased autonomic arousal
      and cognitive or behavioral disturbance following CHI may be coincidental.

PMID- 14591273
TI  - Factor analysis of the WMS-R and the WAIS.
AB  - A principal components factor analysis of the Wechsler Memory Scale-Revised (WMS
      R) and Wechsler Adult Intelligence Scale (WAIS) was performed on 133 patients
      referred for neuropsychological assessment al a university medical center. Six
      factors were selected according to the Scree test, percentage of variance
      extracted, and the meaningfulness of the factors. The factors were labelled as
      follows: Perceptual Organization, Verbal Comprehension, Attention/Concentration,
      Complex Verbal Memory, Verbal Paired-Associate Memory, and Visual Paired
      Associate Memory. The Figurai Memory and Visual Reproduction I & II failed to
      emerge as a factor separate from the Performance subtests of the WAIS. Two verbal
      memory factors were found apart from the Verbal subtests of the WAIS.

PMID- 14591274
TI  - Construct validity of the Continuous Visual Memory Test.
AB  - The construct validity of the Continuous Visual Memory Test (CVMT), a new measure
      of visual recognition memory was evaluated based on the performance of 92
      healthy, normal adults. A series of factor analyses were conducted utilizing
      marker variables for verbal memory, visual memory, attention and concentration,
      and verbal and visual/nonverbal intellectual functions. CVMT acquisition scores
      were associated with verbal and visual/nonverbal intellectual factors as well as
      with attentional ability. The CVMT delayed recognition score was shown to be a
      factorially "pure" measure of visual memory.

PMID- 14591275
TI  - Rey Auditory-Verbal Learning Test: the effects of age and gender, and norms for
      delayed recall and story recognition trials.
AB  - Immediate recall and three measures of delayed memory performance were evaluated
      in 134 healthy adults aged 16-76. Gender of subjects had no Influence on
      performance for any of the acquisition or retention trials. Age influenced
      acquisition as memory load began to exceed five to six words, with older subjects
      exhibiting decreased capacity. There was little loss of information between the
      immediate and delayed recall trials for any age group. Norms for a 30-min delayed
      recall trial, commission errors on delayed recall, and delayed recognition using
      Rey's story recognition procedure are presented, and implications for clinical
      use are discussed.

PMID- 14591276
TI  - Factor analysis and matrix invariance of the HRNB-C category test.
AB  - This study examined the factorial invariance of the six individual Halstead
      Reitan Neuropsychological Battery for Older Children (HRNB-C) Category subtests.
      The test scores for two large samples of learning disabled children were factor
      analyzed. A three-factor solution emerged for each group with a clear pattern of
      variable loadings. Category subtests IV and V load on Factor 1, subtests III and
      VI on Factor 2, and subtests I and II on Factor 3. Variable loadings were not
      only of similar pattern, but also magnitude and sign for both samples. Moreover,
      comparison statistics indicate an excellent fit between the two factor matrices.
      Results support the conclusion that the HRNB-C Category Test measures more than a
      single underlying construct.

PMID- 14591277
TI  - Subclinical hepatic encephalopathy: relationship between neuropsychological
      deficits and standard laboratory tests assessing hepatic status.
AB  - A multivariate analysis of the relationship between biochemical measures of
      hepatic function and neuropsychological assessments of specific cognitive domains
      was performed on data obtained from 74 patients with chronic liver disease and
      subclinical hepatic encephalopathy. Biochemical tests of hepatic protein
      synthesis correlated significantly with measures of impaired language efficiency,
      perceptual speed, and psychomotor efficiency. Biochemical indices of impaired
      processing of nitrogenous compounds correlated with visuopractic deficits.
      Hepatic blood flow indices correlated with language inefficiency. Interestingly,
      biochemical measures of hepatic injury did not demonstrate a significant
      association with any neuropsychological parameter assessed. These results suggest
      that subclinical hepatic encephalopathy is the consequence of a multifactorial
      hepatic dysfunction, and that acute hepatic injury, as assessed by elevation of
      aminotransferases, does not appear to be involved in the pathogenesis of
      subclinical hepatic encephalopathy.

PMID- 14591278
TI  - Memory and learning performances in POW survivors with history of malnutrition
      and combat veteran controls.
AB  - Former prisoners of war (POWs) with histories of malnutrition and body wasting
      were compared on standardized measures of memory and learning with POW survivors
      who sustained less confinement body weight loss and combat veterans of similar
      ages and military assignments. Results showed that POWs who sustained the
      greatest degree of trauma-induced weight loss, or that exceeding 35% of their
      precaptivity body weights, performed significantly worse on four of the five
      Wechsler Memory Scale /3-Revised (WMS-R) indices, showed more rapid rates of
      forgetting on the Visual Reproduction test, and exhibited slower acquisition
      rates and less sophisticated mastery of the learning materials on a modified
      version of the Rey Auditory Verbal Learning Test (AVLT). Given their relatively
      intact performances on measures of general intelligence and attention
      concentration, the POWs with a history of severe malnutrition appeared to
      evidence a pattern of cognitive limitations qualitatively similar to that
      associated with alcoholic Korsakoff's syndrome.

PMID- 14591279
TI  - Are the Rey and Taylor figures equivalent?
AB  - We examined the comparability of the Rey-Osterrieth Complex Figure Test (ROCFT)
      and the Taylor Complex Figure Test (TCFT) as measures of constructional praxis
      and visual recall in a sample of 38 patients who were administered the two
      figures in counterbalanced order. Copy scores did not differ for the two figures.
      There was some evidence that percent recall scores, but not absolute recall
      scores, were higher for the TCFT and more susceptible to proactive interference
      than those for the ROCFT. These results suggest that the two figures yield
      comparable results when copy or absolute recall scores are used, but that the
      TCFT may be easier to recall than the ROCFT when percent recall scores are used.

PMID- 14591280
TI  - Three-dimensional image analysis of trauma-induced degenerative changes: an aid
      to neuropsychological assessment.
AB  - A single case study is presented that depicts three-dimensional (3D)
      reconstruction of the day of injury computerized tomogram (CT) findings with the
      degenerative changes identified by magnetic resonance imaging (MR) 18 months
      postinjury. The method allows the clinician to examine 3D changes in the
      ventricular system as an aid in identifying regions of structural damage in one
      view rather than the need to view multiple images with the traditional two
      dimensional (2D) presentation of CT or MR images. In this case study the
      neuropsychological deficits implicated generalized cerebrocortical dysfunction
      and the 3D image analysis correspondingly indicated generalized parenchymal
      tissue loss. This type of methodology is discussed in terms of furthering the
      neuropsychological-neuroimaging interface.

PMID- 14591285
TI  - The status of clinical neuropsychology.

PMID- 14591284
TI  - Memory remembered: 1970-1991.
AB  - Substantial changes in our knowledge of the neurologic and cognitive processes
      underlying memory disorders have occurred between 1970 and 1991. Models of memory
      stressing consolidation, retrieval, and executive processes have had a positive
      effect on the way memory disorders are assessed in the clinical setting. The
      memory tests available today are superior to those used in the 1970s in terms of
      their sensitivity and selectivity. Similarly, cognitive psychologists have
      successfully used clinical patients to evaluate the validity of their models
      derived from normal subjects. It is concluded that cognitive and clinical
      psychology are not disparate fields; rather, the two have been highly
      interdependent in a positive manner.

PMID- 14591398
TI  - Asymmetrical cognitive differences associated with hemiparkinsonism.
AB  - The question of whether Parkinson's disease (PD) patients who have left (LPD) or
      right (RPD) motor predominance also exhibit cognitive differences is
      controversial. We examined this issue using a neuropsychological battery designed
      to provide a balanced sampling of both right- and left-hemispheric functions. RPD
      patients were impaired relative to LPD patients on verbally mediated tasks (left
      hemisphere function), but there was no group difference for visuospatial tasks
      (right-hemispheric function). In addition, there was a significant correlation
      between the extent of right side motor predominance and performance on verbal
      tasks, but there was no relationship between left side motor symptoms and
      performance on visuospatial tasks. The controversy related to cognitive
      differences in hemiparkinsonism may be due to the balance of the assessment
      procedure, the severity of motor asymmetry, or both.

PMID- 14591399
TI  - Cognitive status of children treated with central nervous system prophylactic
      chemotherapy for acute lymphocytic leukemia.
AB  - Treatment-related cognitive impairments have been reported for survivors of
      childhood leukemia following prophylactic central nervous system (CNS) treatment
      with craniospinal radiation. We examined the neurocognitive status of 46 children
      with acute lymphocytic leukemia (ALL) to assess the impact of a regimen
      consisting of systemic chemotherapy and prophylactic CNS chemotherapy. By
      comparing three groups of ALL children (i.e., patients whose diagnosis was
      recent, patients 1 year postdiagnosis currently receiving CNS prophylactic
      chemotherapy, and off-therapy patients who had been treated with chemotherapy for
      3 years) and their healthy siblings on measures of sequential and simultaneous
      processing, we were able to examine the effects of CNS prophylactic and systemic
      chemotherapy at various points during treatment. Results indicate that the
      children who had received a 3-year course of chemotherapy (off-therapy patients)
      were more impaired on tasks involving right-hemisphere simultaneous processing
      than were sibling controls or ALL children whose diagnosis was recent and whose
      treatment had just begun. Age at diagnosis did not interact with the effects of
      chemotherapy. These findings support the need for continued evaluation of
      cognitive functioning in ALL, children receiving CNS prophylactic chemotherapy to
      identify potential harmful neurocognitive sequelae of treatment.

PMID- 14591400
TI  - Performance of alcoholic and brain-damaged subjects on the Luria Memory Words
      test.
AB  - Verbal memory was evaluated in groups of 36 community controls, 50
      pseudoneurological controls, 50 alcoholics, and 50 brain-damaged patients. All
      participants were men between the ages of 22-61. Groups did not differ in age or
      educational levels (F < 1). Groups were compared on their performance on the
      Luria Memory Words Test. Dependent variables included the number of correct words
      over learning trials, the trial of best performance, and the number of words
      recalled at three delayed trials (2, 8, and 30 min after learning). Brain-damaged
      subjects were inferior to community controls on all measures. Pseudoneurological
      controls were inferior to community controls on delayed recall, but were
      equivalent on measures of learning. Alcoholics were inferior to controls on
      measures of learning but did not differ on measures of recall. Implications
      regarding the underlying deficit in alcoholics' verbal memory, the use and
      interpretation of the Luria Memory Words test, and the use of pseudoneurological
      patients as controls are discussed.

PMID- 14591401
TI  - Differential sensitivity of the WMS to the effects of IQ and brain damage.
AB  - The sensitivity of the Wechsler Memory Scale with Russell's Revision to the
      effects of IQ and brain damage was assessed in groups of brain-damaged (N = 64)
      and nonbrain-damaged (N = 64) subjects. Brain-damaged and nonbrain-damaged
      subjects were divided into subgroups equated on age and IQ for each of three IQ
      ranges (80-89, 90-99, 100-109). Some Wechsler Memory Scale subtests were affected
      only by IQ, others were affected by IQ and brain-damage status, and still others
      were affected only by brain-damage status. Measures of recall efficiency were
      most useful in discriminating brain-damaged and nonbrain-damaged subjects. We
      concluded that specific Wechsler Memory Scale subtests are useful in assessing
      memory deficits in brain-damaged patients.

PMID- 14591402
TI  - Base rates of intersubtest scatter in the old age standardization sample of the
      WAIS-R.
AB  - The Wechsler Adult Intelligence Scale-Revised (WAIS-R) old-age standardization
      sample was analyzed to ascertain normal base rates of intersubtest scatter. The
      range and number of scaled scores that deviated by +/- 3 points from the mean
      were calculated for each subject on the Verbal, Performance, and Full Scale
      subtests. Mean ranges for the total sample were 4.4, 3.4, and 6.5, respectively.
      Ranges were larger for men than women; whites demonstrated more scatter than
      blacks. An increase in scatter emerged on the Verbal and Full Scales as one moved
      from the lowest to the highest education and IQ groups. Over 75% of individuals
      had two, one, or zero subtests that deviated significantly from their WAIS-R mean
      score. Finally, the scatter range for the elderly sample was compared to the
      original WAIS-R standardization sample.

PMID- 14591403
TI  - Test-retest comparability and control subject data for the Rey-Auditory Verbal
      Learning Test and Rey-Osterrieth/Taylor Complex Figures.
AB  - This report presents data from a nonpatient sample considering the test-retest
      reliability and task comparability of the Rey-Osterrieth/Taylor Complex Figures
      and the Rey Auditory Verbal Learning Test. These tasks were presented to normal
      comparison subjects as a component of a large Department of Veterans Affairs
      Cooperative Study on anticonvulsant effects in a manner typical of routine
      clinical use. The results suggest a high degree of reliability for the Rey
      Auditory Verbal Learning Test, supporting its use for test-retest situations.
      However, cautions are discussed for the use of the Rey-Osterrieth-Taylor Complex
      Figure comparisons.

PMID- 14591404
TI  - Long-term vocational functioning after severe closed head injury: a controlled
      study.
AB  - Vocational functioning at least 2 years postinjury was examined in a group of 57
      severely closed-head injured (CHI) patients and 50 nonbrain-injured spinal-cord
      injured (SCI) patients. The two groups were equated on the following preinjury
      parameters: age, education, socioeconomic status (SES), male/female ratio, and
      marital status. The CHI and SCI patients had a similar number of members who were
      employed at follow-up. However, mean follow-up socioeconomic status was
      significantly lower in the CHI group and premorbidly employed CHI patients
      suffered a greater loss of SES than did premorbidly employed SCI patients. These
      results indicate that the degree of vocational impairment after severe CHI goes
      beyond impairment seen with another chronic disabling condition (i.e., SCI) that
      is associated with severe physical impairment but not neuropsychological
      impairment. In the CHI group, the following variables were all correlated with
      SES at follow-up: preinjury education, posttraumatic amnesia duration, degree of
      neuropsychological impairment soon after injury, and emotional adjustment at
      follow-up.

PMID- 14591405
TI  - Trait analyses of the Luria-Nebraska Intellectual Processes, Motor Functions, and
      Memory Scales.
AB  - Trait analyses of the Luria-Nebraska's Intellectual Processes, Motor Functions,
      and Memory Scales were performed using multitrait-multimethod procedures and
      confirmatory factor analysis. Three measures each of intellectual, motor, and
      memory functions were administered to 161 neuropsychiatric patients. Intellectual
      scales (viz., Luria-Nebraska and WAIS-R) were found to have convincing
      discriminant properties, but motor and memory measures demonstrated visibly less
      such robustness. Confirmatory factor analyses supported a three-factor model of
      the 9 x 9 matrix, in which each of the three Luria-Nebraska scales serves as a
      marker for the factors. Issues related to the neuropsychological constructs, test
      construction, and construct validity of measurement procedures employed in
      clinical neuropsychology are discussed.

PMID- 14591409
TI  - A meta-analysis of Halstead-Reitan test performances of non-brain damaged
      subjects.
AB  - Eighteen studies reporting Halstead-Reitan (HR) Neuropsychological Battery test
      performances for over 1000 non-brain damaged subjects were reviewed. Substantial
      empirical normative data is available only for a group of middle-aged adults
      characterized by relatively high intelligence and education. Serious
      methodological flaws in Halstead's original work, changes in the administration
      of HR Battery over the years, as well as variations in subsequent normative data
      suggest the traditional Halstead cutting scores are inappropriate. Norms for a
      composite "meta-sample" were reported. Noting that the HR test scores are valid
      concommitants of neuropsychological dysfunction, specific areas needing empirical
      elucidation are outlined.

PMID- 14591410
TI  - Factor analysis of the Wechsler Memory Scale: is the associate learning subtest
      an unclear measure?
AB  - A factor analysis of the Wechsler Memory Scale (WMS) with 30-minute delayed
      recall scores (percent retained) for the Logical Memory, Visual Reproduction, and
      Associate Learning subtests indicated that this variant of the WMS taps different
      types of learning and memory for new material. With regard to the verbal
      learning/recall subtests, Logical Memory appears to be related to attention/
      concentration ability, while Associate Learning is relatively independent. The
      results also showed that both the easy and hard items from Associate Learning tap
      the same ability, providing evidence that this subtest is a measure of rote
      verbal learning. These results support the clinical utility of the WMS with
      delayed recalls in neuropsychiatric populations.

PMID- 14591411
TI  - Memory in learning disabled children: digit span and the Rey Auditory Verbal
      Learning Test.
AB  - Scores on the Rey Auditory Verbal Learning Test (RAVLT) were compared to WISC-R
      digit span results in a sample of 153 learning disabled students. With
      statistical controls for age and IQ, regression analyses indicated no significant
      relationships between the RAVLT and longest forward span, longest backward span
      and total digit span raw score. Factor analysis of the RAVLT variables, forward
      span, backward span and total digit span raw score yielded three factors that
      were interpreted to represent a long term memory factor, a short-term memory
      factor with high coding demands and a short-term memory factor with low coding
      demands. Conclusions were made regarding the inadequacy of using only digit span
      when making diagnostic statements about the auditory memory functioning of
      learning disabled students.

PMID- 14591412
TI  - Clinical memory tests and everyday memory.
AB  - This study examined the relationship between clinical memory tests and everyday
      memory abilities. Fifty older adults were given clinical memory tests, a battery
      of everyday tasks and a self-report questionnaire of memory problems. The
      interrelationships among these groups of memory assessment measures were studied
      using Pearson correlations and multivariate canonical analysis. The resulting
      intercorrelations and canonical variate loadings were low to moderate in overall
      magnitude. The self-assessment of memory problems had a much lower relationship
      to everyday and clinical memory tasks. The self-assessment of memory for reading
      material had the strongest relationship to clinical memory tests. In general,
      these results moderately support the use of clinical memory tests to predict
      everyday memory ability.

PMID- 14591413
TI  - Neuropsychological performance in dementia of the Alzheimer type and multi
      infarct dementia.
AB  - Neuropsychological performance was examined in patients with dementia of the
      Alzheimer type (DAT) and in age- and education-matched patients with multi
      infarct dementia (MID). Significant differences were observed for FSIQ, VIQ, and
      Picture Completion. This contrasts to no difference in verbal memory, visual
      spatial skills, and sustained attention/concentration. This report illustrates
      that neuropsychological testing of elderly patients is unable to aid in the
      differential diagnosis between clinically similar forms of dementia, and should
      be employed to establish the level of cognitive function to make inferences
      regarding the patient's functional independence.

PMID- 14591414
TI  - Differential diagnosis of dementia and depression in the elderly using
      neuropsychological methods.
AB  - This study examined the utility of the Halstead-Reitan Neuropsychological Battery
      in the differential diagnosis of dementia, major depression, and general
      neurological impairment. Orthogonal contrasts between groups showed superior
      performance for depressives on most Halstead-Reitan subtests. Contrasts between
      organically impaired groups showed that these groups did not differ significantly
      (p >.05) on any of the Halstead-Reitan subtests. A step-wise discriminant
      analysis indicated that on the basis of neuropsychological variables alone,
      demented patients were differentiated from elderly depressed with clinical levels
      of accuracy. However, when neurologically impaired and demented patients were
      considered together in a single group reflecting organic impairment, hits
      increased dramatically. The results were discussed in terms of their implications
      for differentially diagnosing dementia and depression in the elderly.

PMID- 14591415
TI  - Handedness concordance and intelligence discrepancies in identical twins.
AB  - The purpose of this study was to determine if the discrepancy in measured
      intelligence between identical twins concordant for handedness differed
      measureably from the discrepancy between identical twins discordant for
      handedness. If handed concordant and discordant twins did differ in terms of the
      between twin discrepancy in measured intelligence, then one could infer that
      congenital factors had caused dissociation of handedness and measured
      intelligence within a twin set. This finding would support Nagylaki and Levy's
      contention that the found discordance rates for handedness in identical twins is
      a function of "pathogenic" congenital factors disrupting the genetically
      determined handedness pattern. More generally, this finding would also support
      Satz's model with respect to pathological shifts in handedness due to brain
      insult either in utero or perinatally. However, in the current study, eight sets
      of identical twins were examined and no evidence was found to support these
      hypotheses. Instead, in one set where there was a marked discrepancy in measured
      intelligence, handedness could not be determined precisely for the twin with the
      lower intelligence quotient.

PMID- 14591416
TI  - Left-handedness and variant patterns of cerebral organization: a case study.
AB  - A left-middle-cerebral artery infarct in a 51-year-old, nonfamilial left-handed
      man failed to produce aphasia, but did result in imparied visuospatial
      functioning, construction dyspraxia, mild limb dyspraxia, and temporal/sequential
      skill dysfunction. The patient also had severe right-sided sensory and body
      neglect, right-sided hemiparesis, and mildly dysarthric speech. These
      neuropsychological findings strongly suggest a reversed pattern of cerebral
      organization. Posterior anatomical size asymmetries were also reversed, in that
      the right occipitalparietal area was somewhat larger than the left. However, this
      patient's limb dyspraxia followed no known pattern of cerebral organization. His
      dyspraxia suggests that control of complex motor skills in nonfamilial left
      handers may remain a left-hemisphere or bilaterally represented function, even
      when other cognitive abilities are reversed.

PMID- 14591417
TI  - Independent dimensions of hand preference: reliability of the factor structure
      and the handedness inventory.
AB  - Healey, Liederman, and Geschwind (1986) suggested that handedness is not a
      unidimensional trait. They devised a questionnaire with 55 handedness items and 6
      familial hand preference items and administered it to 290 adults. Their analysis
      identified four independent factors underlying hand preference. In the current
      study, the reliability of all but one of the items on the original inventory was
      established by retesting 83 of the original subjects. An additional analysis
      revealed that approximately 2% of the population could be considered to have
      "ambiguous" handedness in the sense that they indicated unstable hand preference
      according to the criteria suggested by Soper and Satz (1984). The reliability of
      the factor structure was evaluated by factor analyzing data from a new sample of
      487 subjects, demographically similar to those in the original sample. All four
      factors reappeared with minor shifts in item loadings. The original and second
      samples were then combined, and four factors were again found, even when the
      sample was reconstructed so that there were equal numbers of males and females.
      On the basis of these new analyses our initial conclusion was confirmed: hand
      preference must be characterized along more than one dimension.

PMID- 14591418
TI  - Cross-validation of a psychometric system for screening neuropsychological
      abnormality in older children.
AB  - The Discriminant Equation (DE) represents a recently developed system for
      screening neuropsychological abnormality in older children. The DE was subjected
      to cross-validation on a sample of 82 child and adolescent psychiatric patients
      referred for a comprehensive neuropsychological assessment. An overall hit rate
      of 79.3% correct classification was found which supported the validity of the DE
      in predicting neuropsychological impairment. The findings are discussed in
      relation to population characteristics and the nature of the criterion to be
      predicted as they may affect the application of neuropsychological screening
      procedures.

PMID- 14591419
TI  - Depression and hemispheric site of cerebral vascular accident.
AB  - In order to investigate the possible role of left and right hemisphere neural
      structures in the manifestation of depression, 50 left brain damaged and 50 right
      brain damaged stroke inpatients were administered the Zung Depression Scale (ZD
      S) during the course of the rehabilitation phase of their treatment. These
      subjects were randomly chosen from all stroke patients receiving rehabilitation
      services who could be administered the ZDS. Approximately 30% of these subjects,
      regardless of the site of lesion, were clinically depressed. The severity of
      depression was independent of demographic factors and time since injury. Right
      brain damaged patients reported significantly more sleep disturbance, psychomotor
      agitation and pervasive sense of sadness. These results were discussed in light
      of previous findings that damaged to the left hemisphere results in greater
      depression. A model of reactive depression that results from neurological
      disability was proposed to partially account for these findings.

PMID- 14591420
TI  - Neuropsychological sequelae of partial complex status epilepticus.
AB  - Relatively little is known about the risk of residual neurological deficit
      following partial complex status epilepticus (PCSE). To address this issue, we
      administered serial neuropsychological assessments and EEGs to a young cocaine
      abuser following the resolution of an extended episode of PCSE. Results suggest
      that PCSE may be associated with prolonged but reversible generalized
      neuropsychological and EEG abnormalities, as well as persistent focal deficits.

PMID- 14591421
TI  - Productive naming and memory in depression and Alzheimer's type dementia.
AB  - Patients with mild to moderate dementia of the Alzheimer's type (DAT), patients
      with major depression, and normal controls completed tests of productive naming
      and verbal recall memory. Both depressed and DAT patients demonstrated reduced
      verbal fluency on productive naming tasks, indicating limited utility of such
      tasks in differential diagnosis. There was a stronger relationship between verbal
      fluency and memory in DAT patients than in depressed patients. The linguistic
      component as well as the requirement for cognitive speed may be important in
      explaining the deficit of DAT patients on productive naming tasks. In contrast,
      the speed component may be particularly important for depressed patients whose
      poor performance may reflect a motivational deficit.

PMID- 14591422
TI  - Neuropsychological changes following the neurosurgical treatment of normal
      pressure hydrocephalus.
AB  - Extracranial shunting of cerebrospinal fluid is a well-known neurosurgical
      procedure for the treatment of normal pressure hydrocephalus. Research indicating
      reasonable success using this technique has been based primarily on subjective
      and global neurosurgical opinion. Given that the treatment carries morbidity
      risks, and that decisions to shunt are related to increasing adaptive
      functioning, attention must be paid to adequate measurement of surgical outcome.
      As part of a larger study, we report pre and postsurgical neuropsychological,
      neuroradiological, and clinical data on hydrocephalic patients, as well as
      presurgical intracranial pressure data. Prior to shunting, increase in
      ventricular dilatation and cerebral atrophy were associated with decreased
      cognitive functioning, gait disturbance, and bladder dysfunction. Following
      shunting, there were significant improvements in neuropsychological functioning
      in terms of attention, concentration, verbal and nonverbal memory, language and
      communication skills, and constructional skills, as well as clinical improvement
      in gait and bladder functioning. Improvement was related to presurgical
      dilatation of the temporal horns of the lateral ventricles and mental status,
      particularly memory functions.

PMID- 14591423
TI  - A survey of common misconceptions about head injury and recovery.
AB  - A survey questionnaire composed of 25 statements about head injury and recovery
      was administered to 221 individuals at a large regional shopping mall. Survey
      items were categorized into domains pertaining to the use of seatbelts, the
      nature of unconsciousness, the nature of amnesia, characteristics associated with
      brain injury, and recovery from brain injury. An additional 8 survey items
      inquired about the sources from which people obtained their knowledge, extent of
      personal experience with brain injury, occupational status, educational status,
      residential status, and their use of seatbelts. Results indicate substantial
      levels of misconception about the nature of unconsciousness, amnesia, and
      recovery, but surprisingly few misconceptions about seatbelts and the effects of
      brain damage. These findings corroborate clinical observations of gross
      misconceptions reported in the literature. Specific misconceptions appeared with
      comparable frequencies across the age groups studied, which indicates that family
      education for patients in rehabilitation needs to target all members of a family,
      rather than a designated primary caregiver.

PMID- 14591424
TI  - A fifteen-item modification of the Fuld Object-Memory Evaluation: preliminary
      data from healthy middle-aged adults.
AB  - A modification of the Fuld Object-Memory Evaluation (FOME) test was developed for
      use with middle-aged adults. To avoid the ceiling effect which occurs when the 10
      item FOME is used with adults in this age group, we made the test more difficult
      by increasing the number of items to 15. We obtained preliminary data on the 15
      item version of the test by administering it to 32 healthy, well-educated adults
      aged 35 to 55. This version of the test was difficult enough so that even high
      functioning adults needed multiple trials to memorize all items. No sex
      differences, and no significant correlations with education or age for any aspect
      of test performance were found. We present mean scores for recall on each trial,
      as well as averaged scores for storage, retrieval, consistent retrieval, and
      recall failure across five trials.

PMID- 14591425
TI  - Differential forgetting in patients with temporal lobe dysfunction.
AB  - Delayed recall performance was investigated in 13 patients with temporal lobe
      epilepsy (TLE) and 13 healthy age-matched controls who were matched on a pairwise
      basis for initial learning on the Selective Reminding test. TLE patients
      performed significantly worse on the 30-minute delayed recall condition despite
      equivalent initial continuous long-term retrieval scores. These data suggest that
      TLE patients forget at disproportionately rapid rates as compared to healthy
      controls despite equivalent initial learning. Consequently, delayed recall may
      increase group discrimination when initial learning levels are similar.

PMID- 14591426
TI  - Construct validity of neuropsychological instrumentation with a learning disabled
      population.
AB  - The construct validity of the Reitan-Indiana Neuropsychological Test Battery (R
      INB)for Children with a learning disabled population was examined. Forty-two
      subjects classified as learning disabled also were administered the Wechsler
      Intelligence Scale for Children-Revised (WISC-R) and Wide Range Achievement Test
      (WRAT) subtests. Factor analysis of the data revealed four factors: verbal
      intelligence, psychomotor speed, achievement, and memory. Evidence from this
      study indicates that the overall construct paradigm as conceptualized by the
      author of the R-INB does not exist. Implications of these findings are discussed.

PMID- 14591427
TI  - Behavioral manifestations of neuropsychological impairment in children with
      psychiatric disorders.
AB  - The behavioral manifestations of neuropsychological impairment were examined in a
      sample of hospitalized boys with psychiatric disorders. The presence of
      neuropsychological deficits was found to be associated with more extensive
      behavior problems regardless of factors such as IQ, socioeconomic status, and
      whether there was a documented history of brain injury. However, the relationship
      applied specifically to younger as opposed to older subjects, and mainly involved
      internalizing rather than externalizing behavior problems. The results are taken
      to suggest that the behavioral manifestations of neuropsychological impairment
      may change with development.

PMID- 14591428
TI  - Diagnostic parameters of an odd-even item short-form of the Luria-Nebraska
      Neuropsychological Battery.
AB  - The current study examined the concurrent validity of a new short form of Luria
      Nebraska Neuropsychological Battery (LNNB). LNNB profiles of 100 subjects of a
      mixed brain damaged, psychiatric and normal pool were obtained from previously
      published sources. Levy corrected correlations among both the odd and even number
      short-forms with the full test ranged from.81 to.90. For the entire sample,
      absolute numbers of scales above the critical level, number of cases following
      within a given range of the critical level, and number of cases within each
      subscale exceeding the critical level were computed. Chi square values revealed
      significant differences only for the visual, reading, and memory subscales
      exceeding the critical level.

PMID- 14591429
TI  - Anoxic encephalopathy: neuroradiological and neuropsychological findings.
AB  - The effects of anoxic brain injury are examined in 12 patients. Neuroradiological
      as well as neuropsychological findings are discussed and clinical guidelines
      offered. The most common neuropsychological profile associated with anoxic brain
      injury is one in which there is generalized cognitive impairment but with
      particular deficits in memory function. The common neuropathological findings are
      manifested by a pattern of diffuse cerebral atrophy as identified by neuroimaging
      techniques. A detailed case study is presented.

PMID- 14591431
TI  - National Academy of Neuropsychology/Division 40 of the American Psychological
      Association Practice Survey of Clinical Neuropsychology in the United States.
      Part II: Reimbursement experiences, practice economics, billing practices, and
      incomes.
AB  - Leaders of the National Academy of Neuropsychology and Division 40 (Clinical
      Neuropsychology) of the American Psychological Association determined that
      current information on the professional practice of clinical neuropsychology
      within the United States was needed. These two organizations co-sponsored a
      national survey of U.S. clinical neuropsychologists that was conducted in
      September 2000. The primary goal of the survey was to gather information on such
      topics as: practitioner and practice characteristics, economic variables (e.g.,
      experience with major third party payors, such as Medicare and managed care),
      practice expenses, billing methods, experiences with Current Procedural
      Terminology (CPT) codes, time spent on various clinical tasks, use of assistants,
      and income. In this second of two articles describing the survey results,
      reimbursement experiences, practice economics, billing practices, and incomes are
      highlighted. Survey results indicate that neuropsychologists frequently have
      difficulty gaining access to membership on managed care panels. For those who
      gain access, managed care companies often limit provision of services; this is
      quite often perceived as negatively affecting quality of patient care. It is very
      common for neuropsychologists to feel obligated to provide more services to
      managed care and Medicare patients than are allowed to be billed to the insurance
      carrier; these hours are typically "written off." Numerous CPT codes are used to
      bill the same clinical service. Awareness of Medicare practice and billing
      expectations is variable among practitioners, as is awareness of public
      aid/Medicaid billing status. Professional income is influenced by years of
      licensed practice, practice setting, gender, types and amounts of non-clinical
      professional activities, and types and amounts of reimbursement sources within
      one's clinical practice. Income of neuropsychologists has only a minimal
      relationship to percentage of clinical practice per week. Within the context of
      prior surveys, neuropsychologists are engaging in more clinical hours per week
      and, nevertheless, compared to data from 1993, are reporting decreased income.
      These and other findings are presented and discussed.

PMID- 14591433
TI  - The lesion(s) in traumatic brain injury: implications for clinical
      neuropsychology.

PMID- 14591434
TI  - Neurobiology and neuropathology underlie the neuropsychological deficits
      associated with traumatic brain injury.
AB  - The neurobiological and neuropathological bases that underlie the
      neuropsychological deficits associated with traumatic brain injury (TBI),
      including mild TBI, are further reviewed. The article provides an update on
      neuroimaging methods and findings in the study of TBI since the author's
      published address of the 1999 Distinguished Neuropsychologist Award of the
      National Academy of Neuropsychology (see Bigler, 2001a). The review addresses and
      answers criticisms raised about the interface of neuroimaging abnormalities and
      neuropsychological deficits, particularly in mild TBI. The article provides
      further guidelines in making the link between neuroimaging findings and
      neuropsychological outcome in the clinical practice of neuropsychology. The
      article also opines on the future role and importance that neuroimaging will play
      in neuropsychological practice, particularly functional neuroimaging methods.

PMID- 14591437
TI  - A confirmatory factor analysis of the WMS-III in a clinical sample with
      crossvalidation in the standardization sample.
AB  - A maximum likelihood confirmatory factor analysis (CFA) of the Wechsler Memory
      Scale-III (WMS-III) was performed by applying LISREL 8 to a general clinical
      sample (n=281). Analyses were designed to determine which of seven hypothesized
      oblique factor solutions could best explain memory as measured by the WMS-III.
      Competing latent variable models were identified in previous studies. Results in
      the clinical sample were crossvalidated by testing all models in the WMS-III
      standardization samples (combined n=1,250). Findings in both the clinical and
      standardization samples supported a four-factor model containing auditory memory,
      visual memory, working memory, and learning factors. Our analysis differed from
      that presented in the WMS-III manual and by other authors. We tested our models
      in a clinical sample and included selected word list subtests in order to test
      the viability of a learning dimension. Consistent with prior research, we were
      also unable to empirically support the viability of the immediate and delayed
      memory indices, despite allowing the error terms between the immediate and
      delayed memory subtests to correlate.

PMID- 14591438
TI  - Preliminary examination of cognitive reserve theory in closed head injury.
AB  - This investigation was designed to provide preliminary support for cognitive
      reserve theory in closed head injury (CHI), and demonstrate the effectiveness of
      using the Oklahoma premorbid intelligence estimate (OPIE) in research and
      clinical activities. Out of a possible 124 consecutive referrals, 26 patients
      (N=26) who underwent neuropsychological assessment following brain injury met
      study inclusion/exclusion criteria. Participants were included if they had exited
      post-traumatic amnesia (PTA), demonstrated uncompromised upper extremity use,
      displayed adequate verbal communication, and were judged capable of completing a
      full neuropsychological evaluation. Participants were divided into a closed head
      injury-negative premorbid history (CHI-) or closed head injury-positive premorbid
      history (CHI+) group based upon premorbid variables (e.g., history of
      alcoholism). Groups did not differ in terms of demographic variables or premorbid
      IQ. Despite having less severe head injuries, the CHI+ group had a greater pre
      post difference for PIQ, and a significantly larger VIQ/PIQ discrepancy than the
      CHI- group. In conclusion, these findings suggest that the CHI+ group had
      diminished cognitive reserve secondary to the aggregate effects of premorbid
      insult, which resulted in greater cognitive decline following an additional
      stressor (i.e., CHI) than what might otherwise be expected from the head injury
      alone.

PMID- 14591439
TI  - The relationship between neuropsychological performance and daily functioning in
      individuals with Alzheimer's disease: ecological validity of neuropsychological
      tests.
AB  - The current study examined the relationship between neuropsychological test
      performance and functional status in 42 individuals diagnosed with Alzheimer's
      disease. A comprehensive battery of cognitive tests was employed in order to
      assess a wide range of neuropsychological abilities. Functional status was
      measured through the use of both a performance-based scale of activities of daily
      living (an expanded version of the Direct Assessment of Functional Status; DAFS,
      Loewenstein et al., 1989), and by a caregiver/informant-based rating scale
      (Instrumental Activities of Daily Living; IADL, Lawton & Brody, 1969). Findings
      suggest that neuropsychological functioning is moderately predictive of
      functional status. Using multiple regression analyses, neuropsychological
      variables accounted for 25% of the variance in the IADL and 50% of the variance
      in the DAFS. Individual domains of both functional measures were also
      significantly predicted by the neuropsychological variables. The findings provide
      evidence of a relationship between neuropsychological test performance and ADLs
      in an Alzheimer disease patient population.

PMID- 14591441
TI  - The Integrated Visual and Auditory Continuous Performance Test as a
      neuropsychological measure.
AB  - The Integrated Visual and Auditory (IVA) Continuous Performance Test (CPT) and
      Neuropsychological Impairment Scale (NIS) were completed by adults diagnosed with
      mild traumatic brain injury (mTBI), adults diagnosed with attention deficit
      hyperactivity disorder (ADHD), and controls. On the IVA CPT, the mTBI and ADHD
      groups performed significantly lower on the full and secondary scales for
      attention and response accuracy. For individual scales, the mTBI and ADHD groups
      showed lower performance on measures of reaction time, inattention, impulsivity,
      and variability of RT. The mTBI and ADHD groups showed similar patterns of
      performance on the IVA. On the NIS, the mTBI and ADHD groups reported more
      neuropsychological symptoms than the control group, and the mTBI group reported
      more neuropsychological symptoms than the ADHD group. The results are discussed
      in regard to changes in cognitive processing and sustained attention in
      individuals diagnosed with mTBI and ADHD.

PMID- 14591440
TI  - Exaggerated MMPI-2 symptom report in personal injury litigants with malingered
      neurocognitive deficit.
AB  - Traditional MMPI-2 validity scales, the Lees-Haley Fake Bad Scale (FBS), and the
      Arbisi and Ben Porath Infrequency Psychopathology Scale (F(p)) were evaluated in
      33 personal injury litigants who had failed forced-choice symptom validity
      testing and other measures of effort in patterns consistent with the Slick,
      Sherman, and Iverson (1999) criteria for definite and probable malingered
      neurocognitive deficit (MND). The FBS was more sensitive to symptom exaggeration
      than F, Fb, and F(p). The definite and probable MND litigants also produced mean
      elevations on MMPI-2 scales 1, 3 and 7 that were significantly higher than those
      produced by various clinical groups including non-litigating severe closed head
      injury, multiple sclerosis, spinal cord injury, chronic pain, and depression.
      These data suggest that MMPI-2 profiles characteristic of malingered injury
      differ from those associated with malingered psychopathology.

PMID- 14591442
TI  - Motor perseveration in geriatric medical patients.
AB  - Perseveration has long been considered as a pathognomonic sign of neurological
      disease, yet, surprisingly, little research exists regarding the accuracy of this
      assumption. This study matched 56 geriatric medical inpatients with 56 inpatients
      with recent cerebrovascular accidents. Participants were given one of two
      measures of general cognition and four Lurian tasks of motor coordination. The
      results suggest that both motor incoordination and across-tasks perseveration
      were associated with decreased cognitive status. After controlling for cognitive
      status, individuals with a neurological history evidenced greater dyscoordination
      and increased perseveration when compared to age-equivalent general medical
      patients. Perseveration in participants with recent strokes appeared more related
      to the amount of neural system disruption as opposed to specific lesion sites.
      Overall, the results suggest that motor incoordination and "stuck-in-set"
      perseveration are more indicative of global than localizable brain dysfunction.
      Possible nonneurologic factors associated with this behavior are also proposed as
      benchmarks for future research.

PMID- 14591443
TI  - Geriatric performance on the Neurobehavioral Cognitive Status Examination
      (Cognistat). What is normal?
AB  - The Neurobehavioral Cognitive Status Examination (Cognistat) is a widely used
      cognitive screening measure that has been utilized in several clinical studies
      with a geriatric population. However, there has been relatively little normative
      research since its original publication. The objective of this study was to
      develop age-corrected norms for Cognistat. One hundred and fifty healthy
      participants aged 60-85 were recruited, all of whom spoke English fluently.
      Twenty-seven peoples met at least one exclusionary criterion and were therefore
      excluded. The participants were administered Cognistat along with measures of IQ,
      depression, alcohol usage, and activity level. Data were not normally
      distributed; therefore, analysis of these data was completed using descriptive
      statistics and the nonparametric bootstrapping technique. Study results provide
      age-corrected profiles that differ significantly from and extend the originally
      published norms.

PMID- 14591444
TI  - The construct validity of the Lees-Haley Fake Bad Scale. Does this scale measure
      somatic malingering and feigned emotional distress?
AB  - The Fake Bad Scale (FBS [Psychol. Rep. 68 (1991) 203]) was created from MMPI-2
      items to assess faking of physical complaints among personal injury claimants.
      Little psychometric information is available on the measure. This study was
      conducted to investigate the psychometric characteristics of the FBS using MMPI-2
      profiles from six settings: Psychiatric Inpatient (N=6731); Correctional Facility
      (N=2897); Chronic Pain Program (N=4408); General Medical (N=5080); Veteran's
      Administration Hospital Inpatient (N=901); and Personal Injury Litigation
      (N=157). Most correlations of the FBS and raw scores on the MMPI-2 were positive
      with correlations among the validity scales being lower than correlations among
      the clinical and content scales. The FBS was most strongly correlated with raw
      scores on Hs, D, Hy, HEA, and DEP. When the more conservative cutoff of 26 was
      used, the FBS classified 2.4-30.6% of individuals as malingerers. The highest
      malingering classification was for the women's personal injury sample (37.9%)
      while the lowest was among male prison inmates (2.3%). Compared to men, in most
      samples, almost twice as many women were classified as malingerers. The results
      indicate that the FBS is more likely to measure general maladjustment and somatic
      complaints rather than malingering. The rate of false positives produced by the
      scale is unacceptably high, especially in psychiatric settings. The scale is
      likely to classify an unacceptably large number of individuals who are
      experiencing genuine psychological distress as malingerers. It is recommended
      that the FBS not be used in clinical settings nor should it be used during
      disability evaluations to determine malingering.

PMID- 14591445
TI  - Multivariate analyses of the profile stability of intelligence tests: high for
      IQs, low to very low for subtest analyses.
AB  - Profile stability involves the consistency of a set of scores over time. That is,
      does a profile of scores change on retesting and does this change affect clinical
      decisions? While psychologists routinely examine the reliability of individual
      scores, little research has examined the stability of a profile or set of scores.
      The first study described in this paper examined potential measures of profile
      stability using a simulation computer program. The results suggest that several
      measures show promise in this context, particularly Cattell's coefficient of
      pattern similarity (r(p)), salient variable similarity index (S), and the D(2)
      coefficient. In the second study, selected measures of profile stability were
      applied to Wechsler test-retest data. The results suggest that profiles composed
      of IQ and index scores demonstrate acceptable stability and can be usefully
      interpreted in clinical and research situations. However, subtest score profiles
      are inherently less stable and provide little useful clinical information.

PMID- 14591447
TI  - MMPI-2 short form proposal: CAUTION.
AB  - The Minnesota Multiphasic Personality Inventory-2 (MMPI-2) is widely used in
      neuropsychology, though its length (567 items) is sometimes prohibitive. This
      study investigated some psychometric characteristics of the 180-item version of
      the MMPI-2 () in order to delineate its strengths, limitations, and appropriate
      scope of clinical application. Limited reliability and poor predictive accuracy
      were recently reported for many of the MMPI-2 short-form scales in a study that
      used 205 brain-injured patients. In the present investigation, we used a
      psychiatric sample (N=186) with normal neurological findings to examine short
      form accuracy in predicting basic scale scores, profile code types, identifying
      high-point scales, and classifying scores as pathological (T>/=65) or normal
      range. The results suggest that, even as applied to neurologically normal
      individuals, the proposed short form of the MMPI-2 is unreliable for predicting
      clinical code types, identifying the high-point scale, or predicting the scores
      on most of the basic scales. In contrast, this short form can be used to predict
      whether the full-scale scores fall within the pathological range (T>/=65). These
      findings suggest that clinicians might be able to salvage a small amount of
      information from the shortened (180-item) version of the MMPI-2 when MMPI-2
      protocols are incomplete. However, clinicians should not use a standard
      interpretive approach with this test, and routine clinical application is
      unwarranted. Future evaluations of short-form validity should provide a more
      detailed examination of individual protocols, including an analysis of the
      frequency of accurate prediction of full-form scores.

PMID- 14591446
TI  - Analyzing the subcortical dementia syndrome of Parkinson's disease using the
      RBANS.
AB  - On mental status examinations, groups of equally impaired patients with
      subcortical (Huntington's disease, HD; Parkinson's disease, PD) or cortical
      (Alzheimer's disease, AD) dementias exhibit different patterns of
      neuropsychological deficits. Using the Repeatable Battery for Assessment of
      Neuropsychological Status (RBANS), classification accuracies of 90% or greater
      have been reported for individual patients with AD or HD. To test the generality
      of the RBANS classification algorithm, we studied patients with dementia (AD and
      PDD) and without dementia (PDND). Classification accuracies were AD: 87%, PDD:
      78%, and PDND: 39%. Comparisons of performance on subtests of the RBANS showed
      that all groups performed more poorly on tests that require motor skill or rapid
      information processing and that memory performance by the PD groups was not
      improved by procedures that enhance encoding and facilitate retrieval. The RBANS
      is useful for discriminating patterns of cognitive impairment in PD and AD, but
      only if the diagnosis of dementia is established independent of the RBANS test
      results. Cognitive slowing is not specific to subcortical dementia and current
      concepts of memory dysfunction in PD may require re-examination.

PMID- 14591449
TI  - Introduction to the NAN 2001 Definition of a Clinical Neuropsychologist. NAN
      Policy and Planning Committee.

PMID- 14591448
TI  - Neuropsychological deficits among patients with late-onset minor and major
      depression.
AB  - Cognitive ability of minor depressed patients (N=28), major depressed patients
      (N=26) and healthy elderly (N=38) was examined cross-sectionally to determine if
      cognitive abilities of patients with late-onset depression decrease with
      increasing severity of disease and if cognitive scores for minor depressed
      patients fall between those of healthy elderly and major depressed patients. A
      pooled within-group principal component analysis of cognitive test scores
      identified five components, three of which showed significant group differences.
      Verbal Recall and Maintenance of Set separated controls from major depressed
      patients and minor from major depressed patients. Executive Functioning separated
      controls from minor depressed patients, and Working Memory was borderline for
      separating controls from major depressed patients. The component representing
      Nonverbal Recognition was not statistically significant. Partial correlations
      controlling for age and education indicate that cognitive performance does
      decrease as severity of depression increases, and the magnitude of the change
      varies from a trend to a significant deficit depending on the cognitive domain.
      This decline in cognitive performance parallels a similar trend observed in
      neuroanatomical studies in which the volume of the frontal and temporal lobes
      decrease with increasing severity of depression.

PMID- 14591450
TI  - A statistical analysis of board certification in clinical neuropsychology.
AB  - In this paper, we use tools from decision theory to evaluate the effectiveness of
      the current psychology board certification process used by the American Board of
      Clinical Neuropsychology (ABCN). These analyses indicate that ABCN's current
      process is likely to be failing to certify too many competently trained
      candidates, and identifying relatively few truly competent neuropsychologists. In
      fact, we estimate that ABCN is only certifying between 16 and 52% of competent
      clinical neuropsychologists. This is in contrast to the processes of the American
      Board of Medical Specialties (ABMS), after which ABCN has indicated that it
      models its examination. ABMS estimates that 89% of all practicing physicians are
      board-certified by one of their member boards. Based on our analyses, specific
      recommendations for change are offered for credentialing the profession of
      neuropsychology.

PMID- 14591451
TI  - Neuropsychological dysfunction in patients with end-stage pulmonary disease: lung
      transplant evaluation.
AB  - There has been a relative absence of studies that have examined the
      neuropsychological profiles of potential lung transplant candidates.
      Neuropsychological data are presented for 134 patients with end-stage pulmonary
      disease who were being evaluated as potential candidates for lung
      transplantation. Neuropsychological test results indicated that a significantly
      greater proportion of the patients exhibited impaired performances on a number of
      Selective Reminding Test (SRT) tasks as compared to the expected population
      frequency distributions for these measures. The highest frequencies of impairment
      were observed on the SRT's Immediate Free Recall (46.43%), Long-term Retrieval
      (41.67%), and Consistent Long-term Retrieval (51.19%) variables. On the Minnesota
      Multiphasic Personality Inventory-2 (MMPI-2)/Minnesota Multiphasic Personality
      Inventory-Adolescent (MMPI-A), patients' mean clinical profile revealed
      elevations on Scales 1 (Hypochondriasis) and 3 (Conversion Hysteria). This
      profile indicated that they were experiencing an array of symptomatology ranging
      from somatic complaints to lethargy and fatigue, and that they may have been
      functioning at a reduced level of efficiency. Findings are discussed in light of
      patients' end-stage pulmonary disease and factors possibly contributing to their
      neuropsychological test performances. Implications for clinical practice and
      future research are also provided.

PMID- 14591452
TI  - The electrophysiological effects of a brain injury on auditory memory
      functioning. The QEEG correlates of impaired memory.
AB  - The effect of a brain injury on the quantitative EEG (QEEG) variables during an
      auditory memory activation condition was examined with 56 normal subjects and 85
      mild traumatic brain-injured (MTBI) subjects. An analysis was conducted on the
      different response patterns of the two groups, the variables which were
      correlated with memory performance in the brain-injured group, and the variables
      which predicted the memory score for the combined two groups (normal and brain
      injured). The three conditions included the input task, the immediate recall, and
      the delayed recall task. The consistent effect of a brain injury was a lowering
      of the connectivity patterns in the beta1 and beta2 frequencies (phase and
      coherences) and increases predominantly in the relative power of beta1 (13-32Hz),
      which were correlated with the differences in recall. There is a subtle shift to
      right hemisphere/right temporal functioning and employment of the higher beta1
      and beta2 frequencies (phase and coherence) in the response pattern of the MTBI
      subject. Memory functioning is predominantly positively correlated with
      connection activity (phase and coherence) and negatively correlated with beta
      activation at specific locations.

PMID- 14591453
TI  - Detection of malingering in assessment of adult ADHD.
AB  - Comparisons of two assessment measures for ADHD: the ADHD Behavior Checklist and
      the Integrated Visual and Auditory Continuous Performance Test (IVA CPT) were
      examined using undergraduates (n=44) randomly assigned to a control or a
      simulated malingerer condition and undergraduates with a valid diagnosis of ADHD
      (n=16). It was predicted that malingerers would successfully fake ADHD on the
      rating scale but not on the CPT for which they would overcompensate, scoring
      lower than all other groups. Analyses indicated that the ADHD Behavior Rating
      Scale was successfully faked for childhood and current symptoms. IVA CPT could
      not be faked on 81% of its scales. The CPT's impairment index results revealed:
      sensitivity 94%, specificity 91%, PPP 88%, NPP 95%. Results provide support for
      the inclusion of a CPT in assessment of adult ADHD.

PMID- 14591454
TI  - Soccer heading frequency predicts neuropsychological deficits.
AB  - This study investigated the presence of neuropsychological deficits associated
      with hitting the ball with one's head (heading) during soccer play. A neuro
      cognitive test battery was administered to 60 male soccer players, high school,
      amateur and professional level, and 12 nonplaying control participants. The
      effects of currently reported heading behavior as well as that of estimated
      lifetime heading experience on neuropsychological test performance were examined.
      Players with the highest lifetime estimates of heading had poorer scores on
      scales measuring attention, concentration, cognitive flexibility and general
      intellectual functioning. Players' current level of heading was less predictive
      of neuro-cognitive level. Comparison of individual scores to age-appropriate
      norms revealed higher probabilities of clinical levels of impairment in players
      who reported greater lifetime frequencies of heading. Because of the worldwide
      popularity of the game, continued research is needed to assess the interaction
      between heading and soccer experience in the development of neuropsychological
      deficits associated with soccer play.

PMID- 14591455
TI  - Measuring personality and emotional functioning in multiple sclerosis: a
      cautionary note.
AB  - Changes in personality and emotional status are common in individuals with
      multiple sclerosis (MS). The purpose of this study was to examine results based
      on the MMPI-2 before and following application of a statistical correction
      procedure (Gass, 1992). This was done to help determine changes in scale score
      elevations when items containing actual physical symptoms are identified and
      statistically removed. Twenty-eight participants with MS were administered the
      MMPI-2, then retested 1 year later. Stability of MMPI-2 scores over time was
      demonstrated. Results showed that when the correction procedure was applied to
      the MMPI-2, eight standard clinical scale scores dropped an average of 6.66 T
      score points. Significant differences were obtained between standard MMPI-2
      scored profiles and corrected profiles on Scales 1-3 and 8. Cautious
      interpretation of MMPI-2 results for neurological samples was indicated. This
      study extended prototypic research by using patients with MS, examining the
      stability of results over time (1 year), and introducing a more reliable method
      of deriving standard T-scores in the correction procedure.

PMID- 14591457
TI  - Can the National Health and Nutrition Examination Survey III (NHANES III) data
      help resolve the controversy over low blood lead levels and neuropsychological
      development in children?
AB  - The National Health and Nutrition Examination Survey III (NHANES III) was
      designed to provide national estimates of the health and nutritional status of
      the United States population aged 2 months and above. A Youth data subset
      includes individuals from ages 2 months to 16 years totaling 13,944 individuals.
      Lanphear, Dietrich, Auinger, and Cox [U.S. Department of Health and Human
      Services, Public Health Reports, Public Health Report 2000, Vol. 115, p. 521]
      examined these data and concluded that deficits in cognitive and academic skills
      associated with lead exposure occur at blood lead concentrations of less than
      5microg/dl. Attempts to replicate and extend these findings reveal serious
      shortcomings in the NHANES III data that center around missing data, odd
      distributions of blood lead levels as well as cognitive and academic scores, and
      potential inaccuracies in the data collection itself. A review of these issues is
      presented along with a series of empirical analyses of the data under multiple
      sets of assumptions leading to the conclusion that the NHANES III data are
      inherently inadequate for use in addressing neurodevelopmental issues. Policy
      issues and scientific issues related to cognitive and other neurodevelopmental
      phenomena should not be considered on the basis of the NHANES III Youth dataset.

PMID- 14591458
TI  - Detecting malingered performance on the Wechsler Adult Intelligence Scale.
      Validation of Mittenberg's approach in traumatic brain injury.
AB  - This study assesses the effectiveness of the Wechsler Adult Intelligence Scale
      (WAIS) performance validity markers devised by Mittenberg et al. [Prof. Psychol.:
      Res. Pract. 26 (1995) 491] in the detection of malingered neurocognitive
      dysfunction (MND). Subjects were 65 traumatic brain injury (TBI) patients
      referred for neuropsychological evaluation. Twenty-eight met the Slick et al.
      [Clin. Neuropsychol. 13 (1999) 545] criteria for at least probable MND. The
      control group was comprised of 37 patients without external incentive and who
      thus did not meet the Slick et al. criteria. All subjects completed the Wechsler
      Adult Intelligence Scale-Revised (WAIS-R or WAIS-III). The discriminant function
      score (DFS) and the vocabulary-digit span (VDS) difference score were calculated
      and sensitivity, specificity, and predictive power were examined for several cut
      offs for each marker individually and the two combined. Classification accuracy
      for the DFS was acceptable and better than for VDS. The use of the two markers in
      combination resulted in no incremental increase in classification accuracy.
      Issues related to the clinical application of these techniques are discussed.

PMID- 14591459
TI  - A validation of multiple malingering detection methods in a large clinical
      sample.
AB  - The purpose of this study is to further previous research that has shown that
      common neuropsychological tests can do "double duty" as test of
      motivation/malingering. Using a large clinical sample of 796 participants, it was
      found that the nine neuropsychological tests (when used together) were able to
      correctly identify litigant and nonlitigating groups. Failure on any two of the
      malingering tests suggested motivational/malingering issues. The groups consisted
      of mild, moderate, and severe traumatic brain-injured patients; chronic pain,
      depressed, community controls, and "malingering actors." Institutionalized and
      noninstitutionalized patient performance were also examined. This method showed
      83% sensitivity and 100% specificity. A 0% false positive rate was found,
      suggesting good reliability especially in litigating settings. A group of
      patients for whom this method of motivational assessment might not be appropriate
      was also identified.

PMID- 14591460
TI  - Evaluation of the accuracy of two regression-based methods for estimating
      premorbid IQ.
AB  - Two premorbid IQ estimation procedures were compared in a normal, non-brain
      impaired sample and a clinical sample of known brain-impaired individuals. The
      methods used for comparison were the purely demographically based regression
      index (DI) developed by and the Oklahoma Premorbid Intelligence Estimate (OPIE)
      equation by, which uses demographic information combined with current performance
      tasks. The data for the normal sample were gathered from the WAIS-R
      standardization sample of 1880 subjects. The clinical sample was 100 patients
      with known cognitive impairment who had been referred to a private
      neuropsychology practice. The DI appeared to provide the most clinical utility as
      an estimate of premorbid IQ in a cognitively impaired sample. Significant
      differences between the two methods for specific locations of brain injury were
      not observed.

PMID- 14591461
TI  - Development and validation of a web-based neuropsychological test protocol for
      sports-related return-to-play decision-making.
AB  - The Concussion Resolution Index (CRI) is an online assessment tool designed to
      track resolution of symptoms following sports-related concussion. The CRI is
      composed of six subtests measuring reaction time, visual recognition, and speed
      of information processing. Three factors are derived from the subtests: Simple
      Reaction Time (SRT), Complex Reaction Time (CRT), and Processing Speed (PS).
      Multiple alternate forms within subtests afford simple, reliable, assessment of
      change, relative to a baseline test completed by an athlete. The test also
      assesses self-reported neurophysiological symptoms at the time of injury and
      tracks resolution of these symptoms. The data demonstrate the CRI is a valid and
      reliable measure of cognitive performance in a relatively heterogeneous group of
      athletes aged 13-35. Two methods of statistical analysis for assessing change
      from baseline were compared to establish a psychometric basis for return-to-play
      decision-making: the Reliable Change Index (RCI) and multiple regression.
      Multiple regression was more accurate than the RCI in determining a decline in
      performance relative to the baseline.

PMID- 14591462
TI  - Inhibitory capacity in adults with symptoms of Attention Deficit/Hyperactivity
      Disorder (ADHD).
AB  - Adult participants for the current study were placed into one of two groups
      depending on whether they manifested either high or low symptom levels of
      Attention Deficit/Hyperactivity Disorder (ADHD) as determined by the Wender Utah
      Rating Scale. Participants were also assessed on a battery of cognitive tasks as
      well as symptoms of depression, anxiety and substance abuse. The ADHD symptom
      groups were comparable in age and symptoms of depression, anxiety, and substance
      abuse. Adults with greater ADHD symptomatology performed more poorly on cognitive
      measures of response inhibition (the Stop-Signal task) and visual attention,
      compared to those with fewer ADHD symptoms. Regression analysis indicated the
      Stop-Signal task accounted for a greater proportion of the variance of ADHD
      symptomatology than any other cognitive variable. The conclusions from the
      findings are discussed in relation to self-regulation model of ADHD.

PMID- 14591463
TI  - Psychometric properties of the Mid-Range Expanded Trail Making Test. An
      examination of learning-disabled and non-learning-disabled children.
AB  - By systematically varying the stimuli within the Mid-Range Trail Making Test
      (MTMT), it may eventually be possible to isolate the cognitive demands of this
      test. Toward this end, the Mid-Range Expanded TMT (METMT) was developed by adding
      five new forms to the original forms A and B. To insure its appropriateness for
      clinical and experimental use, the current study sought to quantify the
      psychometric properties of this new test. The results indicate that the METMT is
      reliable and has adequate construct, criterion, and factoral validity. The
      results also cross-validated the findings of Davis et al. [J. Clin. Psychol. 45
      (1989) 423.], suggesting that brief neuropsychological evaluations can
      effectively differentiate normal learners from learning-disabled children. The
      present study suggests that the MTMT is robust to alterations of its stimulus
      dimensions. Preliminary METMT normative data are presented.

PMID- 14591464
TI  - Detecting neuropsychological malingering: effects of coaching and information.
AB  - Concerns that patients presenting for neuropsychological assessment may not be
      putting forth maximum effort during testing has prompted the development of
      measures designed to detect malingering and incomplete effort. Two of these
      measures are the Computerized Assessment of Response Bias-97 (CARB-97) and Word
      Memory Test (WMT). Despite widespread use of these instruments, no study has been
      published determining the vulnerability of neuropsychological malingering
      measures to explicit coaching or brain injury information. The present study,
      using analog participants, found that the CARB-97 and WMT differentiate "normal"
      from "malingered" instructional sets, and show little difference between nai;ve
      and coached malingering efforts. There was also little difference between
      providing brain injury information and a no-information condition, but when
      effects were present, the information group generally scored worse. Further, it
      was found that response times (RTs), in addition to items correct, may also be
      effective in detecting those who are not giving their full effort.

PMID- 14591465
TI  - The Recognition Memory Test Examination of ethnic differences and norm validity.
AB  - The possibility of racial bias in neuropsychological test materials has received
      increasing attention in recent years. The purpose of the present study was to
      investigate whether an own-race recognition bias would provide an advantage for
      Caucasian participants over African American participants on the Faces subtest of
      the Recognition Memory Test (RMT). Thirty Caucasian and 30 African American
      undergraduates completed the RMT, Shipley Institute of Living Scale (SILS), and
      Symbol Digit Modalities Test (SDMT). No significant group difference was found on
      RMT Faces. However, mean RMT Faces scores for both groups were below the 10th
      percentile in spite of average scores on the SDMT and SILS. A second study was
      conducted to further examine the validity of the RMT norms for this age range
      (i.e., 18-24) and to provide 2-week test-retest reliabilities. The mean RMT Faces
      subtest score was 39.78 (10th percentile), and 28% of the sample scored at or
      below the fifth percentile. Test-retest reliabilities were.63 and.64 for RMT
      Words and Faces, respectively. Results of these studies suggest that re
      examination of the current norms for RMT Faces is warranted for adults aged.

PMID- 14591466
TI  - Diagnostic accuracy of the Structured Inventory of Malingered Symptomatology
      (SIMS) in detecting instructed malingering.
AB  - This article addresses the psychometric properties of the Dutch translation of
      the Structured Inventory of Malingered Symptomatology (SIMS) when administered to
      undergraduate psychology students as well as psychiatric inpatients. Findings
      show that this SIMS version possesses good test-retest reliability and internal
      consistency. Also, simulation findings indicate that undergraduate students
      instructed to simulate pathology display higher SIMS scores than either normal
      controls or psychiatric inpatients. Data pooled over several samples (n=298)
      yielded sensitivity, specificity, and positive predictive power (PPP) rates that
      were all relatively high (>/=0.90). All in all, our findings provide a basis for
      cautious optimism regarding the usefulness of the SIMS as a screening tool for
      malingering.

PMID- 14591467
TI  - The reliability of cluster and switch scores for the Controlled Oral Word
      Association Test.
AB  - This study examined the interrater reliability and temporal stability of a
      scoring system developed by Troyer, Moscovich, and Winocur [Neuropsychologia 11
      (1997) 138] to measure clustering and switching on verbal fluency (VF) tasks such
      as the Controlled Oral Word Association Test (COWAT) [Benton, A.L., Hamsher, K.,
      & Sivan, A.B. (1983). Multilingual aphasia examination (3rd ed.). Iowa City, IA:
      AJA Associates]. Seven independent raters scored COWAT protocols of 125 healthy
      participants in accordance with the rules proposed by Troyer et al. Intraclass
      coefficients were near perfect, ranging from.96 for total number of clusters
      to.99 for total number of switches. Test-retest reliability coefficients (n=55)
      were poor to modest (r=.47 for clusters, r=.58 for switches, and r=.70 for total
      words). Significant improvement in performance was observed across most COWAT
      indices, suggesting a practice effect. Modifications to test administration are
      suggested to improve the stability of cluster and switch scores, as well as other
      variables for further study.

PMID- 14591468
TI  - Neuropsychologists' abilities to determine the predictive value of diagnostic
      tests.
AB  - The diagnostic utility of a test is relative to the base rate of the diagnosis in
      the population of interest. The extensive use of tests in neuropsychological
      assessment makes knowledge of the relevance of base rates in this context an
      important issue. Professional and associate members of the National Academy of
      Neuropsychology (NAN; n=279) answered questions involving (1) a simple use of
      base rates in the absence of additional diagnostic information, (2) sensitivity
      and specificity, and (3) positive predictive value (PPV) presented in either a
      probability or frequency format. Although the majority of participants answered
      correctly the simple base rate, sensitivity, and specificity questions, only 8.6%
      answered correctly the PPV question presented in a probability format versus
      63.0% correct using a frequency format. These results are discussed in terms of
      education about the importance and application of base rate information and
      difficulties applying base rate information in practice.

PMID- 14591469
TI  - The critique of the HRNES in the Handbook of Normative Data for
      Neuropsychological Assessment.
AB  - While providing excellent coverage for the norms used in a number of
      neuropsychological tests, the Handbook of Normative Data for Neuropsychological
      Assessment (Handbook) singles out for rejection a single set of norms, the
      Halstead Russell Neuropsychological Evaluation System (HRNES). The stated grounds
      for this rejection were not applied to any other of the several hundred sets of
      norms included in the book. The HRNES was rejected even though it fully meets the
      Handbook's selection criterion for tests to be included in the book.

PMID- 14591471
TI  - The intermediate visual and auditory continuous performance test as a
      neuropsychological measure.
AB  - The Intermediate Visual and Auditory (IVA) Continuous Performance Test (CPT) and
      Neuropsychological Impairment Scale (NIS) were completed with adults diagnosed
      with mild traumatic brain injury (mTBI), adults diagnosed with Attention Deficit
      Hyperactivity Disorder (ADHD), and controls. On the IVACPT, the mTBI and ADHD
      groups performed significantly lower on the full and secondary scales for
      attention and response accuracy. For individual scales, the mTBI and ADHD groups
      showed lower performance on measures of reaction time, inattention, impulsivity,
      and variability of RT. The mTBI and ADHD groups showed similar patterns of
      performance on the IVA. On the NIS, the mTBI and ADHD groups reported more
      neuropsychological symptoms than the control group and the mTBI group reported
      more neuropsychological symptoms than the ADHD group. The results are discussed
      in regard to changes in cognitive processing and sustained attention in
      individuals diagnosed with mTBI and ADHD.

PMID- 14591470
TI  - Quantitative measures of memory malingering on the Wechsler Memory Scale--Third
      edition in mild head injury litigants.
AB  - Wechsler Memory Scale-Third edition (WMS-III) performance in 25 mild traumatic
      brain injury (TBI) litigants who met the criteria for probable malingered
      neurocognitive dysfunction (MND) was compared with 50 nonmalingering subjects.
      The base rate for probable MND in the population studied was 27%. Overall,
      malingerers showed globally depressed memory function. They returned
      significantly poorer scores than nonmalingerers on all WMS-III indexes and
      subtests, and on selected WMS-III index difference scores and intelligence-memory
      difference scores. Using the minimum score returned in the nonmalingerers as the
      cut-off for malingering, the delayed auditory recognition memory tasks were
      highly effective in detecting malingering. Raw scores below 43 on the auditory
      recognition-delayed (AR-D) subtest or below 18 on word list II-recognition,
      identified around 80% of the malingerers. In a group of 50 severe TBI litigants,
      only a very small proportion (i.e., <10%) returned scores below the cut-offs for
      malingering for the mild TBI subjects.

PMID- 14591473
TI  - Detecting malingering on the WAIS-III. Unusual Digit Span performance patterns in
      the normal population and in clinical groups.
AB  - In several studies, suppressed Digit Span performance has been proposed as a
      potential marker for deliberately poor performance in a neuropsychological
      evaluation. The purpose of this study was to document Digit Span performance
      patterns in the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III; )
      standardization sample and selected clinical groups. Base rate tables were
      generated for the Digit Span scaled score, longest span forward, longest span
      backward, and the Vocabulary-Digit Span difference score. Cut-off scores for
      suspecting negative response bias were proposed, and clinical case examples were
      used to illustrate these scores.

PMID- 14591474
TI  - The significance of sensory-motor functions as indicators of brain dysfunction in
      children.
AB  - Sensory-perceptual and motor functions are closely dependent on the integrity of
      the brain and nervous system. Standardized tests have been developed to assess
      these functions, but such tests are not routinely used to evaluate children who
      are suspected of having a neuropsychological basis for their difficulties. Higher
      level functions (such as verbal and academic abilities, executive functioning,
      etc.) are obviously important in producing successful performances, but the brain
      and nervous system correlates of these abilities are less well defined than the
      correlates for sensory-motor abilities. Our contention is that tests from these
      two general areas (higher-level and lower-level aspects of brain functioning) can
      be used effectively in a complementary manner to evaluate individual children.
      The first step in this process is to evaluate formal sensory-motor tests and to
      assess their validity as a brief preliminary examination used to differentiate
      between brain-damaged and control children. The results of this study
      demonstrated striking differences between the groups and indicated that sensory
      motor testing might serve very effectively, when used in conjunction with higher
      level tests, to identify those children whose higher-level impairment is due to
      brain impairment rather than a lack of environmental opportunities or advantages.

PMID- 14591475
TI  - Effects of blood pressure on neuropsychological functioning in Alzheimer's
      disease.
AB  - Blood pressure is often lower among patients with Alzheimer's disease (AD)
      compared to nondemented older adults. Lower blood pressure in AD correlates with
      reduced cerebral blood flow and cortical atrophy, but its effect on
      neuropsychological functioning is unclear. We assessed the effects of blood
      pressure on tests of dementia severity, attention, memory, language, verbal and
      nonverbal reasoning, motor/psychomotor functioning, and activities of daily
      living (ADL) among probable AD patients (n=609). As hypothesized, lower systolic
      blood pressure (SBP) predicted reduced attention (Digits Forward and Backward),
      memory (Visual Reproduction I), and ADLs. Unexpectedly, lower pulse pressure (SBP
      DBP) predicted greater dementia severity (Mini-Mental State Examination, MMSE),
      attention (Digits Forward and Backward), memory (Logical Memory I and Visual
      Reproduction I), and ADLs. These findings may reflect a tendency for less
      severely demented patients to exhibit normal age-related changes in blood
      pressure, whereas abnormal patterns may develop with increased dementia severity.

PMID- 14591476
TI  - Learning following prenatal alcohol exposure: performance on verbal and visual
      multitrial tasks.
AB  - Verbal Learning deficits have been reported following prenatal alcohol exposure
      (PAE). This study examined verbal and visual multitrial learning in children with
      fetal alcohol syndrome (FAS) or fetal alcohol effects (FAE) and controls matched
      on age and gender from the same community. In this study, the FAS/FAE group's
      immediate memory on the Verbal Learning and Visual Learning tasks from the Wide
      Range Assessment of Memory and Learning (WRAML) was significantly weaker than
      that of the control group. Although the FAS/FAE group also recalled significantly
      less information after a delay, they did retain an equivalent proportion of the
      visual and verbal information as compared to the control group. Thus, the overall
      pattern of performance on both verbal and visual measures was consistent with
      that observed in previous studies of Verbal Learning: despite weaker learning,
      the FAS/FAE group's relative retention of information was no different than that
      of controls.

PMID- 14591477
TI  - Demographic effects on the Trail Making Test in a drug abuse treatment sample.
AB  - Appreciation of the importance of screening for cognitive impairment among
      substance abusing populations has increased in recent years. In this article,
      demographic effects on the Trail Making Test (TMT), a test often used for
      screening for cognitive impairment, are examined in a sample of patients in drug
      abuse treatment programs. A sample of 5,619 males and 2,902 females was drawn
      from electronic files of data from the Drug Abuse Treatment Outcome Study
      (DATOS). The DATOS was a naturalistic cohort study that collected data from 1991
      to 1993 in 96 programs in 11 cities in the US. Data were analyzed to determine
      the effects of demographic variables on the two parts of the TMT in this large
      sample of patients. Consistent with previous research, demographic variables such
      as age, gender, education level, and ethnicity were statistically significantly
      related to both TMT Parts A and B. More importantly, however, the percentage of
      variance accounted for was quite small. These results suggest that, while clearly
      present, demographic effects on the TMT are weak.

PMID- 14591478
TI  - Use of the CBDI to detect malingering when malingerers do their "homework".
AB  - Previous research has demonstrated the ability of the Cognitive Behavioral
      Driver's Inventory (CBDI) to detect neuropsychological malingering [Arch. Clin.
      Neuropsychol. 12 (5) (1997) 491.], however, the present study tests if the CBDI
      can discern malingerers when they are "coached" on how brain-damaged patients
      actually perform on neuropsychological tests. Ninety-eight college student
      participants were given financial incentive to fake brain damage on the CBDI.
      Fifty-three of these subjects were "coached" and 45 were not. The coached and
      uncoached subjects performed indistinguishably on the CBDI. Both types of
      malingerers were discernable from real brain-damaged patients (99.2% accuracy
      area under the sensitivity-specificity curve). Further, CBDI profiles of five
      actual plaintiffs judged to be malingering were compared to CBDI profiles of
      experimental subjects. In each case, the malingering plaintiff's CBDI profile was
      indistinguishable from that of malingering experimental subjects and was clearly
      discernable from that of actual brain-damaged patients.

PMID- 14591479
TI  - Partial cross-validation of the Wechsler Memory Scale-Revised (WMS-R) General
      Memory-Attention/Concentration Malingering Index in a nonlitigating sample.
AB  - The Wechsler Memory Scale-Revised (WMS-R) malingering indices proposed by
      Mittenberg, Azrin, Millsaps, and Heilbronner [Psychol Assess 5 (1993) 34.] were
      partially cross-validated in a sample of 200 nonlitigants. Nine diagnostic
      categories were examined, including participants with traumatic brain injury
      (TBI), brain tumor, stroke/vascular, senile dementia of the Alzheimer's type
      (SDAT), epilepsy, depression/anxiety, medical problems, and no diagnosis. Results
      showed that the discriminant function using WMS-R subtests misclassified only
      6.5% of the sample as malingering, with significantly higher misclassification
      rates of SDAT and stroke/vascular groups. The General Memory Index
      Attention/Concentration Index (GMI-ACI) difference score misclassified only 8.5%
      of the sample as malingering when a difference score of greater than 25 points
      was used as the cutoff criterion. No diagnostic group was significantly more
      likely to be misclassified. Results support the utility of the GMI-ACI difference
      score, as well as the WMS-R subtest discriminant function score, in detecting
      malingering.

PMID- 14591480
TI  - The effect of ageing on confrontational naming ability.
AB  - The change in confrontational naming ability accompanying normal ageing has been
      widely studied. However, inconsistent findings have been reported. Our study
      reexamined this issue by adopting both accuracy and response latency as indices
      for reflecting the effect of normal ageing on confrontational naming. Sixty
      normal and healthy, Cantonese-speaking Chinese volunteered for this study. Thirty
      of them belonged to the Young Age Group (YOUNG; M=19.77 years, S.D.=1.5 years)
      and 30 to the Old Age Group (OLD; M=71.47 years, S.D.=6.51 years). The instrument
      used was the Chinese Naming Test (CNT) for measuring confrontational naming. The
      findings indicated that younger people performed much better than older people on
      the test in terms of accuracy as well as response latency. The observed different
      performance between the young and old participants could not be explained by
      their different levels of education. No gender difference in performance on the
      test was observed. Our findings supported our initial hypothesis that normal
      ageing does have a negative impact on confrontational naming. The decline in
      naming ability with ageing may be multifactorial.

PMID- 14591481
TI  - Neuropsychological testing of high school athletes. Preliminary norms and test
      retest indices.
AB  - This study provides preliminary norms and test-retest indices on a brief battery
      of neuropsychological tests administered to a sample of 60 male and 40 female
      high school athletes. Forty-eight subjects completed retesting 8 weeks later.
      Analyses of baseline scores indicate that girls outperform boys on selected
      measures of processing speed and executive functions [Wechsler Adult Intelligence
      Scale-III (WAIS-III) Digit Symbol, Trails B, and Controlled Oral Word Association
      Test (COWAT)]. Test-retest reliability was low and varied widely among the tests.
      There were no gender differences in test-retest reliability. Reliable Change
      Indices (RCIs) were computed on the test-retest data for use in clinical
      interpretation. These preliminary results indicate that caution should be used in
      interpreting neuropsychological test data from high school athletes. The current
      findings indicate that separate norms for boys and girls are warranted. Caution
      should be used in interpreting discrepancies from baseline scores as a result of
      what may turn out to be poor test-retest reliability in this population.

PMID- 14591846
TI  - Cognitive assessment of geriatric schizophrenic patients with severe impairment.
AB  - There is evidence that some elderly patients with chronic schizophrenia
      experience marked impairments in cognitive functioning. Assessment of these
      patients may be difficult with traditional neuropsychological measures. The
      purpose of the present study was to determine if cognitive functioning could be
      validly assessed with the Alzheimer's Disease Assessment Scale-Late Version
      Cognitive factor score (ADAS-L Cog) in patients whose scores on the Mini-Mental
      State Examination (MMSE) reflect profound cognitive impairment. Patients with
      MMSE scores from 0 to 10 were selected from a larger database. Neuropsychological
      instruments designed for the assessment of mild to moderate dementia were found
      to be inadequate in this profoundly impaired population, due to floor effects. In
      contrast, there was a significant relationship between ADAS-L scores and several
      criterion measures, including the MMSE (R=-.71, P<.001), the Social Adaptive
      Functions Evaluation (SAFE) social functions scale (R=.47, P<.001), and the
      negative symptom total score of the Positive and Negative Syndrome Scale (PANSS)
      (R=.412, P<.001). The MMSE was somewhat less strongly correlated with both social
      functions (R=-.401, P<.001) and the negative symptom total score of the PANSS (R=
      .366, P<.001). These results suggest that cognition can be reliably and validly
      assessed with instruments such as the ADAS-L that are designed for the assessment
      of severely impaired patients.

PMID- 14591847
TI  - Sensitivity and specificity of the Rey Dot Counting Test in patients with suspect
      effort and various clinical samples.
AB  - The Rey Dot Counting Test was administered to 100 patients with suspect effort
      drawn from two separate settings (personal injury/disability, n=86; prison
      hospital, n=14) and to 251 subjects in nine clinical groups (head injury,
      learning disability, right and left cerebrovascular accident, schizophrenia,
      older normals, depressed elderly, and mild and moderate dementia). Sensitivity of
      cut-offs for individual test scores (mean grouped dot counting time, ratio of
      mean grouped to ungrouped dot counting time, and number of errors) differed
      markedly across the two suspect effort groups (e.g., 28-100%), indicating that
      noncredible patients drawn from different settings employ somewhat differing
      approaches in their fabrication of cognitive symptoms. Use of a cut-off of > or
      =17 applied to a combination score (mean ungrouped dot counting time+meangrouped
      dot counting time+number of errors) resulted in 100% sensitivity in the forensic
      suspect effort group and 75% sensitivity in the civil litigation/disability
      suspect effort group, while maintaining specificity of > or =90% for the clinical
      groups combined (excluding moderate dementia).

PMID- 14591848
TI  - Validity of the behavior rating inventory of executive function in children with
      ADHD and/or Tourette syndrome.
AB  - The dynamic, multidimensional nature of executive function (EF), thought to be
      characteristically impaired in those with attention deficit hyperactivity
      disorder (ADHD), has been challenging to operationalize and assess in a clinical
      setting [Barkley, R. A. (1997). ADHD and the nature of self-control. New York:
      Guilford Press.]. Gioia, Isquith, Guy, and Kenworthy [Gioia, G. A., Isquith, P.
      K., Guy, S. C., & Kenworthy, L. (2000) Behavior Rating Inventory of Executive
      Function. Odessa, FL: Psychological Assessment Resources.] developed the Behavior
      Rating Inventory of Executive Function (BRIEF) to address these concerns. In
      order to provide concurrent validity information on the BRIEF, parents of 76
      children (ADHD=18; Tourette syndrome (TS)=21; TS+ADHD=17; controls=20) completed
      the BRIEF, additional behavior rating scales and interviews, measures of
      psychoeducational (PE) competence, and performance-based measures of EF. Both
      ADHD and TS+ADHD groups were rated as more impaired (P<.0001) than the other
      groups on the five primary BRIEF indices. BRIEF index scores showed no
      significant correlation with performance-based EF or PE measures, with the
      exception of math achievement; however, the BRIEF showed a strong relationship
      with interviews and other parent rating measures of behaviors seen in ADHD.
      Future attempts to validate the BRIEF should focus on differences within subtypes
      of ADHD (e.g., inattentive, combined subtypes), and separating ADHD from other
      clinical groups in which EF is reported to be a problem.

PMID- 14591849
TI  - The impact of heroin on frontal executive functions.
AB  - Our study examined the impact of heroin on frontal executive functioning in three
      cognitive domains, namely attention, impulse control, and mental flexibility and
      abstract reasoning. It was hypothesized that heroin addiction would lead to
      deficits in these three cognitive domains. Fifty-five participants, 30 heroin
      addicts, and 25 normal controls were invited to participate in this study. Each
      participant was individually interviewed for demographic data and tested by the
      selected neuropsychological measures. The findings indicate that heroin addiction
      has a negative effect on impulse control, while attention and mental
      flexibility/abstract reasoning ability were not affected.

PMID- 14591850
TI  - Neuropsychological test performance of children with ADHD relative to test norms
      and parent behavioral ratings.
AB  - Neuropsychological test performance relative to published norms and parent
      ratings was assessed archivally among 78 children with attention deficit
      hyperactivity disorder (ADHD). Despite average to low average IQs and academic
      achievement, the children performed poorly relative to test norms on most
      measures sensitive to fronto-executive functioning (span of attention, sustained
      attention, response inhibition, and working memory). They also performed poorly
      on most memory tests requiring free recall/retrieval, a skill dependent in part
      on intact frontal/subcortical functioning. In contrast, performance fell within
      the average to low average range on all measures of retention, although some mean
      scores fell significantly below normative means. In addition, higher levels of
      inattention or hyperactivity as assessed from parent reports were associated with
      worse performance on neuropsychological tests. That is, correlations calculated
      between neuropsychological test scores and parent ratings on the Adaptive
      Behavior Scale (ABS) were both significant at the P<.05 level and in the expected
      direction in 33% of the analyses for ratings of attention, in 43% of the analyses
      for ratings of hyperactivity, and in 5% of the analyses for ratings of
      persistence.

PMID- 14591851
TI  - Malingering on subjective complaint tasks: an exploration of the deterrent
      effects of warning.
AB  - Assessing patient's subjective experience of illness is an important component of
      neuropsychological assessment. This information can be assessed using
      standardized self-reported complaint (SRC) checklists and may have specific
      applications in the assessment of malingering. Previous research suggests that
      subjective complaints can be faked under some circumstances, however, the extent
      to which this occurs when assessments are made using standardized SRC measures is
      less well understood. In addition, if complaints can be faked, this raises the
      question: What might reduce the likelihood of faked symptom reports? In this
      study, we randomly allocated 60 first-year undergraduate subjects to one of the
      three conditions: malingering, malinger-with-warning, and control. Using a
      repeated-measures analogue design, we assessed differences between groups on
      selected SRC measures. The measures used were the Neuropsychological Symptoms
      Checklist (NSC), the General Health Questionnaire-30 (GHQ-30), and the
      Depression, Anxiety, and Stress Scales (DASS). We expected to find that SRC
      measures would be vulnerable to faking, but also that warning malingerers about
      the possibility of detection would reduce faking behavior. Further, control group
      scores on SRC measures were calculated to produce preliminary complaint base rate
      data for these tests. Our results showed that SRC measures were vulnerable to
      faking. In addition, contrary to expectations, we found that warnings did not
      significantly deter malingering, although we observed that a trend in the
      expected direction and future studies with a larger sample size or a modified
      warning may be needed to further investigate warning efficacy. Broader
      implications of these findings are discussed in light of deterrence theory and
      recent debate over the use of SRC measures in the assessment of malingering.

PMID- 14591852
TI  - The unexamined lie is a lie worth fibbing: neuropsychological malingering and the
      Word Memory Test.

PMID- 14591853
TI  - Executive function deficits in patients with dementia of the Alzheimer's type: a
      study with a Tower of London task.
AB  - A growing number of studies report a deterioration of the executive function (EF)
      in dementia of the Alzheimer type (DAT). To evaluate EFs in DAT, a new version of
      the Tower of London (TOL) task, originally developed by Shallice (1982), was
      adapted. The new version of the test was built up in its easiest possible feature
      in order to be administrable to early- or middle-stage demented patients.
      Seventeen DAT patients, and 17 controls matched for age and sex, were
      administered the TOL. The protocol followed a "hierarchical paradigm," that is,
      simpler problems were embedded in more complex, subsequent problems. Results
      showed that DAT patients were impaired compared to controls. Both control and DAT
      groups showed a decrease in percentage of success rate in relation to the number
      of movements required by the task. On the more complex problems, the performance
      of DAT subjects was proportionally more impaired. Qualitative analysis revealed
      that rule breaking was a salient performance feature of the DAT group. These
      findings are consistent with the presence of an EF deficit in DAT.

PMID- 14591854
TI  - Clock face drawing in children with attention-deficit/hyperactivity disorder.
AB  - The clock drawing test has been found to be sensitive to visual-spatial
      perception, graphomotor skills, verbal reasoning, and executive functioning in
      adult patient populations, as well as frontal lobe maturation in normal children.
      Our study is among the first to assess the use of clock drawing as a
      neuropsychological measure in the pediatric population. Participants included 41
      children with attention-deficit/hyperactivity disorder (ADHD) and 41 normal
      controls, ages 6-12 years, matched for age, gender, and handedness.
      Conceptualization of time and construction of the clock face were assessed
      separately using a scoring system normed on school-age children in an earlier
      study. Children with Predominantly Inattentive Type were found to perform
      similarly to those with Combined Type of ADHD. However, children with ADHD,
      regardless of subtype, performed significantly poorer than controls. Qualitative
      analysis of performance revealed errors that were subsequent to poor planning
      during task execution, consistent with executive dysfunction commonly present in
      children with ADHD. Further, multiple regression analysis demonstrated that a
      neuropsychological measure of executive functioning was predictive of clock
      construction performance in children with ADHD. Constructional praxis and
      receptive vocabulary also were predictive of clock construction ability.
      Implications of these findings are discussed.

PMID- 14591855
TI  - The Adaptive Digit Ordering Test: clinical application, reliability, and validity
      of a verbal working memory test.
AB  - In the face of ample experimental evidence on the importance of working memory
      capacity for everyday life, there is a growing need for measures suited for
      clinical assessment of working memory. For this purpose, the Adaptive Digit
      Ordering Test (DOT-A), a new version of a digit ordering test introduced by
      Cooper et al. [Brain 114 (1991) 2095], was developed in analogy to the Digit
      spans. In Study 1, we investigated DOT-A performance in patients with Parkinson's
      disease (PD) and patients with frontal lobe damage, as these groups often exhibit
      working memory impairments within the framework of executive dysfunctions. In
      comparison with matched controls, both patient groups showed reduced performance
      in DOT-A but not in Digit span performance. This pattern was found to be
      particularly sensitive for patients with PD. In Study 2, DOT-A performance was
      assessed in 50 healthy subjects carefully selected according to demographic
      criteria in order to ensure representativity. Parallel test and split-half
      correlations indicated sufficient reliability of the DOT-A. Concurrent validity
      was confirmed by significant correlation with a well-established working memory
      test (two-back task). We conclude that DOT-A is a promising diagnostic
      instrument, and its economy and direct comparability to the Wechsler Digit spans
      and high sensitivity for patient populations make it especially well-suited for
      assessment in clinical practice.

PMID- 14591856
TI  - Verbal Paired Associates tests limits on validity and reliability.
AB  - The Verbal Paired Associates (VPA) subtest from the Wechsler Memory Scale-III
      (WMS-III) is one of the most widely used instruments for assessing explicit
      episodic memory performance. The normative data for the VPA subtest in the WMS
      III manual show clear evidence of performance ceiling effects that limit the
      usefulness of this instrument. For this reason, we developed a new 15-item VPA
      test and we report normative data obtained from a partially stratified sample of
      351 healthy adults between 18 and 91 years of age. Only a small fraction of
      participants obtained perfect scores on our new Paired Associates test. The
      results show the expected large age-related decline in memory acquisition,
      indexed by performance on the first study test trial, together with a much
      smaller age effect on learning across trials. The results also show that
      performance on the Paired Associates test is related to education, verbal IQ, and
      to a lesser extent, participants' sex. We provide various equations for precise
      predictions of Paired Associates test performance.

PMID- 14591857
TI  - MMPI-2 profiles of patients with intractable epilepsy.
AB  - MMPI-2 profiles of 93 presurgical intractable epilepsy patients were examined
      using Ward's method of cluster analysis. Three clusters were identified. The
      means of each cluster suggest that 45% of the sample had minimal psychological
      complaints, 30% presented with generalized clinical elevations, and 25% of the
      patients had profiles of intermediate elevations with a tendency to emphasize
      somatic complaints and/or depression. Gender, age of seizure onset, and seizure
      laterality were not found to be uniquely associated with the cluster profiles.
      Further examination of correlates of group membership is warranted to provide
      information for treatment planning.

PMID- 14591858
TI  - Interactive influences on BVRT performance level: geriatric considerations.
AB  - We examined the interactive influence of specific demographic and diagnostic
      variables on Benton Visual Retention Test (BVRT) performance in three commonly
      presenting groups of older adults. Cross-sectional data from three archival
      samples were utilized: "normals" (n=156), "normals with memory concerns" (n=435),
      and a "mixed neurologic" group (n=196). In both normal groups, as well as in a
      "no/low deficit" neurologic subgroup, we confirmed that the higher one's age, the
      lower their BVRT accuracy, while the higher one's level of education, the greater
      their BVRT accuracy (at least through age 84). For normal subjects, gender had no
      impact on BVRT performance. Variability in BVRT performance increased
      consistently, but not significantly, through age 85.

PMID- 14591859
TI  - Clinical neuropsychology 1970-1990: a personal view.
AB  - In 1970, I assessed the status of a "new discipline", clinical neuropsychology,
      and optimistically predicted growth and expansion over the next decades. A
      current assessment in 1990 indicates that the dramatic increase in the number of
      clinical neuropsychologists and in the scope and magnitude of their professional
      functioning far exceeds my expectations of two decades ago. Further, there is
      every indication that clinical neuropsychology will continue to be a challenging,
      vital, and expanding profession.

PMID- 14591860
TI  - Neuropsychological assessment, neuroimaging, and clinical neuropsychology: a
      synthesis.
AB  - The history of lesion analysis in neuropsychology is reviewed. Contemporary
      methods of brain imaging and electrophysiological analysis also are reviewed with
      an emphasis on problems associated with lesion identification and quantification.
      New methods for lesion analysis are discussed including three-dimensional
      imaging. The challenge is given to neuropsychology to place a greater emphasis on
      quantitative measures of lesions analysis in clinical research.

PMID- 14591861
TI  - The effects of intrauterine cocaine exposure: transient or teratogenic?
AB  - The use of cocaine and its smoked derivative, crack, is increasing in America.
      Among those affected are neonates of women who use cocaine during pregnancy. This
      paper examines the potential effects of maternal cocaine use upon the developing
      fetus emphasizing neuropsychological and behavioral effects including those that
      typically persist into early childhood and beyond. Empirical research should
      continue to explore the effects of maternal cocaine use focusing on whether or
      not the many detrimental effects of cocaine use during pregnancy are transient,
      directly teratogenic, or indirect and due to prolonged hypoxia.

PMID- 14591862
TI  - Reply to Reitan: unexamined premises and the evolution of clinical
      neuropsychology.

PMID- 14591863
TI  - A counterpoint to Reitan's note on the history of clinical neuropsychology.

PMID- 14591986
TI  - Confirmatory factor analysis of the Wechsler Memory Scale-Revised standardization
      sample.
AB  - A maximum likelihood confirmatory factor analysis was preformed by applying
      LISREL to the variance-covariance matrix obtained from standardization of the
      Wechsler Memory Scale-Revised (WMS-R) (N = 316). Analyses were designed to
      determine which of seven hypothesized factor solutions could best explain memory
      function as measured by the WMS-R. Competing latent variable models were
      identified in previous exploratory and confirmatory factor analytic studies. The
      measurement error matrix was set to remove method variance shared by the
      immediate and delayed trials of the same subtest. Hypothesized factors were fixed
      and allowed to correlate. Results indicated that a three-factor model, including
      Attention/Concentration, Immediate and Delayed Memory, explained 91% of the score
      variance and produced a significantly better fit than the Attention/Concentration
      -General Memory or Attention Concentration--Visual/Verbal Memory solutions.
      Findings support previous work suggesting that the WMS-R measures separate memory
      functions, and that the verbal/nonverbal Index distinction may not be a viable
      one.

PMID- 14591987
TI  - Effects of chronic cocaine abuse on memory and learning.
AB  - Sixteen chronic (M = 5 years) weekly cocaine users who were at least 10 days (M =
      20 days) abstinent were compared to age, education, race, and gender matched
      controls on the California Verbal Learning Test, Wechsler Adult Intelligence
      Scale-Revised (WAIS-R) Vocabulary, and Block Design. Subjects with developmental
      disorder, neurological, psychiatric, or other substance abuse history were
      excluded. Cocaine subjects learned and recalled fewer words than controls, but
      did not differ on IQ. Results suggested significant residual impairment in verbal
      learning efficiency subsequent to chronic cocaine use that results from memory
      storage difficulties rather than attentional impairment or general intellectual
      reduction. A dose-response relationship is suggested.

PMID- 14591988
TI  - The Indented Paragraph Reading Test in the assessment of left hemi-neglect.
AB  - We investigated the validity of the Indented Paragraph Reading Test (IPRT),
      designed to assess left hemi-neglect (LHN) in reading behavior, with regard to
      education effects, scoring properties, and sensitivity to recovery of LHN. The
      IPRT was administered aspart of a larger battery to 50 right-hemisphere stroke
      patients approximately 1, 2, 3, and 7 months post-stroke if, and only if, the
      patient demonstrated LHN on the previous test battery. Contrary to expectations,
      performance on the IPRT was not correlated with education and even patients with
      minimal formal education were able to complete the test. We demonstrated that the
      author's suggested scoring criterion was valid and sensitive to the presence of
      LHN as well as to its recovery over time.

PMID- 14591989
TI  - Disordered thinking and cerebral dysfunction: laterality effects, language, and
      intellectual functions.
AB  - This report examines two types of thought disorder, bizarre-idiosyncratic
      thinking and concreteness, in relation to cerebral impairment and psychotropic
      medication status. Results do not support lateralized dysfunction as a
      contributing factor for either form of thought disorder. Relationships between
      specific areas of neuropsychological deficit and thought disorder indicate that
      intellectual and arithmetic functions are more closely associated with bizarre
      idiosyncratic thinking. Further, there were no specific neuropsychological
      impairments related to concrete thinking, nor was medication status related to
      either type of thought disorder. Problem-solving or reasoning affects logical
      orderly cognitive processes more reliably than it affects abstract thinking.
      Differences between these findings and other research are discussed from the
      standpoint of how both types of thought disorder are conceptualized and assessed,
      and how this may influence clinical indications for the use of psychoactive
      medications.

PMID- 14591990
TI  - Can perseverative responses on the Wisconsin Card Sorting Test be scored
      accurately?
AB  - Anecdotal reports have led to questions concerning the reliability and accuracy
      with which Heaton's Wisconsin Card Sorting Test perseverative response criteria
      can be applied. In addressing this question, this study found that practicing
      clinicians were less accurate than "experts" and two groups of novices. A
      computer scoring system allowed one novice to score with "expert" level accuracy.
      Utilization of this system should increase scoring accuracy. However, the program
      cannot accurately score protocols when the response cards are in nonstandard
      order. Solutions to this problem are discussed.

PMID- 14591991
TI  - Effects of repeated neuropsychological assessments.
AB  - The effects of repeated administrations of neuropsychological instruments were
      evaluated in a group of chronic cigarette smokers who served as control subjects
      in a larger research project. Subjects performance on 13 neuropsychological
      variables across four assessments was evaluated using trend analyses.
      Statistically significant results were obtained on the Logical and Figurai Memory
      Subtests of the Wechsler Memory Scale (Form I-Russell's Revision) Part B of the
      Trail Making Test and the Grooved Pegboard Test (preferred hand). Of the
      remaining seven variables the Speech Sounds Perception Test, the Seashore Rhythm
      Test and Simple Auditory Reaction Time were highly consistent across all four
      assessments. The implications of these findings in clinical practice and research
      settings are addressed.

PMID- 14591992
TI  - Normative implications of the relationship between reading vocabulary and Boston
      Naming Test performance.
AB  - The 60-item Boston Naming Test (BNT) was published in 1983 with norms described
      as provisional. One recent finding (Thompson & Heaton, 1989) suggests that verbal
      intelligence, and the Wechsler Adult Intelligence Scale (WA1S)-Revised Vocabulary
      subtest, in particular, is strongly correlated with BNT performance, and that
      education is moderately so. High false-positive rates for naming deficit may
      conceivably result from the application of the published norms with subjects of
      lower verbal abilities or limited educational backgrounds. To further explore the
      relationship of naming to other verbal abilities, analyses were undertaken of the
      correlations between Level 7-9 Gates-MacGinite Reading Vocabulary Test (G-MRVT)
      and BNT data from 97 schizophrenic, bipolar, and normal subjects. Reading
      vocabulary is strongly correlated with BNT performance, and the nature of this
      relationship is essentially the same across the three diagnostic groups.
      Application of the published norms would have resulted in a high false-positive
      rate for naming deficit in all groups among subjects with reading vocabularies
      equivalent to twelfth grade or less. As a word-recognition based reading
      exercise, the G-MRVT is likely to provide a brain-compromise-resistant index
      against which the adequacy of naming performances can be assessed. Accordingly, G
      MRVT based BNT performance expectation guidelines are presented for use as a
      complement to the published norms. Other implications are discussed.

PMID- 14591993
TI  - Discriminating between simulated malingering and closed head injury on the
      Wechsler Memory Scale-Revised.
AB  - We tested the hypothesis that malingering is distinguished by poorer performance
      on recognition relative to recall tasks by evaluating the ability of discriminant
      functions to distinguish between 89 subjects simulating malingering and 44
      subjects with a history of closed head injury (CHI) on the Wechsler Memory Scale 
      Revised (WMS-R). Functions with good accuracy in discriminating between
      simulated malingerers and controls in prior studies did not have adequate
      specificity when applied to the CHI group. A newly derived discriminant function
      achieved overall classification accuracy of 79% for the malingering versus CHI
      groups on cross-validation, with 79% sensitivity (true positives for malingering)
      and 80% specificity (true negatives for closed head injured). A complex
      performance pattern on seven WMS-R subtests distinguished malingering subjects
      from those with CHI, but did not support the recognition versus recall
      hypothesis. The malingering pattern involved: (a) power performance on two
      relatively (but inconspicuously) easy tasks dependent on immediate recall (Visual
      Reproduction I and Visual Memory Span); (b) better performance on two relatively
      (but inconspicuously) easy tasks dependent on immediate recall (Visual Paired
      Associates I and Digit Span); (c) poorer performance on two relatively difficult
      delayed tasks (Logical Memory II and Visual Paired Associates II); and (d) better
      performance on another difficult task involving delayed recall (Visual
      Reproduction II).

PMID- 14591997
TI  - The role of imagery in the rehabilitation of neglect in severely disabled brain
      injured adults.
AB  - Two single case studies are presented examining the effects of imagined limb
      activation in participants with unilateral visual neglect and severe physical
      disabilities. The first study employed a standard ABBABBA design where the
      participant was asked to imagine making movements with his left arm during the
      intervention conditions. Neglect was systematically assessed at each stage on the
      following measures: line bisection, star cancellation, and a scanning task.
      Performance during intervention conditions was compared to baseline conditions.
      The results suggest that imagined activation of the left arm may significantly
      reduce the severity of left neglect. The second study used an ACCABBACCABBA
      design. The participant was asked to imagine making movements with his left arm
      during the intervention conditions and with his right arm during the control
      conditions. The measures used in this study were line bisection, star
      cancellation, and letter cancellation. The results showed that there was no
      reduction in neglect symptoms associated with imagined left arm movements, but
      there was an increase associated with imagined right arm movements. This was
      thought to represent either a specific difficulty imagining left arm movements or
      a difficulty in combining left arm imagined arm movement with task completion.
      Overall, the results support the hypothesis that imagined movement can affect the
      presentation of neglect, and that the effects are specific to the arm that is
      used. This technique may prove useful to the clinical practitioner working with
      severely disabled brain-injured adults with neglect for whom conventional
      intervention techniques are inappropriate.

PMID- 14591998
TI  - Intraindividual variability as an indicator of malingering in head injury.
AB  - The utility of various measures of malingering was evaluated using an analog
      design in which half the participants (composed of three groups: naive healthy
      people, professionals working with head-injured people, individuals who suffered
      a head injury but not currently in litigation) were asked to try their best and
      the remainder was asked to feign believable injury. Participants were assessed
      with the Reliable Digit Span (RDS) task, the Victoria Symptom Validity Test
      (VSVT), and the Computerized Dot Counting Test (CDCT) on three separate occasions
      in order to determine whether repeat administration of tests improves prediction.
      The results indicated that regardless of an individual's experience,
      consideration of both level of performance (particularly on forced-choice symptom
      validity tasks) and intraindividual variability holds considerable promise for
      the detection of malingering.

PMID- 14591999
TI  - Cognitive skill learning and aging: a component process analysis.
AB  - The ability to acquire a cognitive and motor skill was investigated in 20 older
      and 20 younger participants using repeated testing on the Tower of Toronto (TT)
      puzzle, a variant of the Tower of Hanoi. Explicit memory, perceptual priming, and
      sustained attention were also assessed. Older subjects exhibited a defective
      cognitive skill performance despite the fact that cognitive skill learning
      suffered little or no impairment. Poor problem-solving ability, diminished
      attention, fatigue, defective explicit memory, and meta-cognitive processes were
      likely to play a limiting role. Factors interfering with the generation of
      reliable goal structures are likely to prevent cognitive skill learning, giving
      important cues for future cognitive remediation.

PMID- 14592000
TI  - High-functioning autism and schizophrenia: a comparison of an early and late
      onset neurodevelopmental disorder.
AB  - Autism and schizophrenia are separate neurodevelopmental disorders that share a
      number of interpersonal and cognitive deficits. The symptoms of autism first
      appear during early life while schizophrenic symptoms do not typically appear
      until adolescence at the earliest. Efforts have been made to characterize the
      pattern of cognitive function in both disorders, and certain resemblances have
      become apparent such as deficits in abstract reasoning and the more complex
      aspects of memory and language. The present study provided a comparison of
      cognitive function between the two disorders. The autistic sample consisted of
      well-diagnosed individuals with high-functioning autism (IQ> or =70). The
      schizophrenic sample was divided into four subgroups using Ward's method of
      cluster analysis. Participants received the Wechsler Adult Intelligence Scale
      Revised (WAIS-R), the Halstead Category Test, the Trail Making test, and the
      Wisconsin Card Sorting test (WCST). The profile of the autism sample was compared
      with the four schizophrenia cluster profiles. The autism group resembled only one
      of the schizophrenia clusters, with both showing elevations on the WAIS-R
      Information and Block Design subtests and depressions on Comprehension and Digit
      Symbol. It was concluded that individuals with high-functioning autism have a
      cognitive profile that resembles that of an empirically derived subgroup of
      schizophrenia patients but that does not resemble profiles found in other
      schizophrenia subgroups. The pattern itself, marked by a relatively depressed
      score on the Comprehension subtest among the Verbal subtests and a relatively
      elevated score on Block Design among the Performance subtests, has been
      characterized in the past as a prototypic profile for high-functioning autism.

PMID- 14592001
TI  - Executive functioning in obsessive-compulsive disorder, unipolar depression, and
      schizophrenia.
AB  - The present study investigated whether schizophrenic, unipolar depressive, and
      obsessive-compulsive psychiatric patients show a distinguishable profile in tasks
      considered sensitive to frontal lobe functioning. Three psychiatric samples, each
      comprising 25 patients with little symptomatic overlap, were compared to 70
      healthy controls. Participants completed several executive tasks (Wisconsin Card
      Sorting Test (WCST), verbal fluency, digit span, Stroop, and Trail-Making).
      Except for age, which was entered as a covariate, subjects did not differ in any
      sociodemographic background variable. Healthy controls showed superior
      performance relative to depressive and schizophrenic patients who exhibited
      comparable deficits in all tasks. Obsessive-compulsive disorder (OCD) patients
      revealed dysfunctions in the Trail-Making Tests A and B and in the fluency task.
      Dysfunctions in the domains of working memory, verbal fluency, distractibility,
      and concept formation were not confined to a specific psychiatric population.

PMID- 14592002
TI  - Angle paradigm: a new method to measure right parietal dysfunctions in anorexia
      nervosa.
AB  - BACKGROUND: A functional disturbance of the right parietal cortex (PC) is
      supposed to be responsible for the distorted body image in patients with anorexia
      nervosa (AN). Based on this assumption, we investigated changes in haptic
      perception with a new experimental design. METHOD: Thirty-two subjects (16 AN
      patients and 16 healthy controls) were asked to readjust a given angle adjustment
      without visual feedback. This arrangement allowed to measure the deviation of the
      adjusted angle from the locked angle on an interval scale. RESULTS: AN patients
      performed worse when they were asked to readjust the angle with the right hand,
      i.e., the deviation of the readjusted angle from the given angle was higher
      compared to the healthy controls for right side tasks. CONCLUSIONS: The
      capacitive strain of the right PC is substantially stronger in right side tasks
      with the consequence that the functionally disturbed right PC of AN patients
      cannot provide enough processing resources.

PMID- 14592003
TI  - Estimating premorbid intelligence: comparison of traditional and contemporary
      methods across the intelligence continuum.
AB  - The present investigation compared the North American Adult Reading Test (NAART),
      Wide Range Achievement Test-3 (WRAT-3) Reading subtest, Barona, and Oklahoma
      Premorbid Intelligence Estimate Best (OPIE) premorbid intelligence estimates in
      64 chronic pain patients across three intelligence ranges. Results for the entire
      sample revealed that the NAART, Barona, and OPIE Best equations overestimated
      Wechsler Adult Intelligence Scale-Revised Full Scale IQ (WAIS-R FSIQ), while the
      WRAT-3 underestimated FSIQ. When the sample was divided into three intelligence
      ranges, the OPIE more accurately classified individuals with above average
      intelligence, while the WRAT-3 more accurately classified individuals with below
      average intelligence. Three methods (NAART, OPIE, and WRAT-3) provided relatively
      equivalent classifications of individuals in the average intelligence range. The
      Barona method tended to systematically under- and overestimate FSIQ across the
      intelligence continuum. These results suggest the potential utility of using
      different estimation methods for individuals in different IQ ranges, and speak to
      the need for development of estimation methods that incorporate current reading
      ability with best performance and demographic variables.

PMID- 14592005
TI  - The relation of the Halstead-Reitan neuropsychological battery to functional
      daily living skills in geriatric patients.
AB  - This study investigated the nature of the relationship between neuropsychological
      tests, the Halstead-Reitan Battery, and a measure of everyday living ability, the
      Community Competence Scale. The sample consisted of 40 geriatric patients
      referred for suspected dementia. The results indicated that neuropsychological
      tests were moderately predictive of measures of functional daily living skills.
      Although some specific neuropsychological measures, or combination of measures,
      were more predictive of particular functional daily living skills, their
      relationship did not necessarily follow logical or theoretical expectations.
      Thus, while it may be safe for neuropsychologists to make predictions about a
      patient's global capacity to function independently, predictions regarding
      specific functional daily living skills may be unwarranted.

PMID- 14592006
TI  - Do neurocognitive measures differentiate Attention Deficit Disorder (ADD) with
      and without hyperactivity?
AB  - Recent behavioral and neuropharmacological evidence suggests that the
      differentiation of children with Attention Deficit Disorder with (ADD/H) and
      without hyperactivity (ADD/WO) may reflect an appropriate nosological
      distinction. There is also evidence that attention-regulatory mechanisms possibly
      associated with anterior-posterior processes may be independently implicated in
      these children. To test this hypothesis, 100 clinic-referred children were
      reliably diagnosed as ADD/H (n = 48). ADD/WO (n = 26) and as having an
      internalizing disorder (n = 26) for inclusion as a clinic-control (CC) group. An
      analysis of covariance using Full-Scale IQ, chronological age, and the number of
      conduct-disorder symptoms provided little support for such a behavioral
      distinction using selected WISC-R, Luria-Nebraska-Children's Revision, and
      reaction-time variables. Alternative conceptualizations, possibly reflecting
      deficient right-hemispheric processes in ADD/H, may provide more productive
      avenues for research in distinguishing deficient neurocognitive processes in
      subtypes of ADD.

PMID- 14592007
TI  - Left-hemisphere dysfunction in autism: what are we measuring?
AB  - This study sought to investigate the left hemisphere deficit hypothesis regarding
      autism. A group of 15 autistic youngsters between the ages of 8 and 13 years was
      compared with a group of 15 mentally retarded youngsters matched for age and IQ
      on a set of measures presumed to be sensitive to neuropsychological dysfunction.
      The results suggested that this sample of autistic youngsters is best
      characterized by bilateral neuropsychological involvement, affecting left
      hemisphere functioning predominantly but not exclusively. The findings of this
      and other such studies seem to be somewhat determined by the varied samples and
      assessments employed in the research. The practice of selecting tests which
      presumably tap left or right cerebral functions is highly inferential, and
      warrants concern, particularly when assessing complex cognitive functioning in
      autistic individuals.

PMID- 14592137
TI  - Hope for the PLMs quagmire?

PMID- 14592138
TI  - Cataplexy: 'REM-atonia or tonic immobility'?

PMID- 14592139
TI  - Race, iron status and restless legs syndrome.

PMID- 14592140
TI  - REM on demand: an editorial on 'Elicitation of sleep-onset REM periods in normal
      individuals using the sleep interruption technique (SIT)'.

PMID- 14592141
TI  - Cataplexy: 'tonic immobility' rather than 'REM-sleep atonia'?
AB  - BACKGROUND: Cataplexy, a sudden loss of muscle tone in response to strong
      emotions, is the most specific symptom of narcolepsy. It is currently thought to
      be due to disturbed rapid eye movement (REM) sleep regulation, and portrayed as
      REM sleep atonia occurring at the wrong time. However, there are several
      arguments against including cataplexy in the 'state boundary control' hypothesis.
      It does not explain why cataplexy is triggered by emotions, and recent studies in
      narcoleptic dogs showed that REM sleep regulatory mechanisms were in fact intact
      in these animals. METHODS: We review the literature on the REM sleep dissociation
      theory, discuss the merits and demerits of the theory, and propose an alternative
      hypothesis explaining cataplexy. RESULTS: Cataplexy may represent an atavism
      (recurrence of an ancestral characteristic) of tonic immobility. Tonic immobility
      (TI) denotes a condition in which an animal is rendered immobile when faced with
      danger. Arguments in favor of the TI hypotheses are that it explains the
      emotional triggering. Furthermore, centers regulating narcolepsy and TI are both
      located in the lateral hypothalamic area. Finally, several drugs known for their
      ameliorating effect on cataplexy reduce the frequency and duration of TI in
      animals. CONCLUSION: Cataplexy may be due to a mechanism different from the other
      clinical symptoms of narcolepsy.

PMID- 14592142
TI  - Elicitation of sleep-onset REM periods in normal individuals using the sleep
      interruption technique (SIT).
AB  - Use of the sleep interruption technique (SIT) to elicit sleep onset REM periods
      (SOREMPs) in normal individuals is introduced along with its theoretical bases,
      empirical findings, and potential applications. Capitalizing upon the circadian
      and ultradian nature of REM sleep, the SIT has been developed to examine various
      psychophysiological characteristics related to REM sleep. The SIT allows us to:
      (1) obtain SOREMPs at the discretion of the researcher; (2) avoid the
      contaminating effects of preceding non-REM (NREM)-REM stage ordering on
      subsequent target sleep episodes; and (3) obtain many REM episodes in a short
      time by repeating the sleep interruptions. The SIT has been applied in several
      studies, such as examination of physiological precursors to REM periods,
      correlates of dream mechanisms, and induction of sleep paralysis in normal
      individuals. Guidelines for eliciting SOREMP using the SIT, including the
      parameters to be manipulated, are provided, e.g. NREM duration before sleep
      interruption, time of night of awakenings, duration of sleep interruption and
      tasks employed. Directions for further research such as determining optimal type
      of task to promote SOREMP occurrences, generalization of SOREMP as usual REM
      periods, and forms of SOREMP occurrences under different conditions in normal
      individuals and clinical patients are discussed. Finally, possible future uses of
      the SIT, including combining this technique with new technologies, are also
      suggested.

PMID- 14592143
TI  - Periodic limb movement in a community population detected by a new actigraphy
      technique.
AB  - BACKGROUND: Periodic limb movements (PLMs) have been studied in both community
      and sleep clinic populations using polysomnography. An alternative detection
      method is actigraphy. Our aims were to determine the frequency of PLMs, measured
      by actigraphy in a community sample, and to assess the relationships of PLMs with
      age, gender, and reported sleep-related symptoms. METHODS: Volunteers had
      bilateral foot actigraphy (Cambridge Neurotechnology) at home and completed sleep
      questionnaires. Actigraphy was scored for PLMs per hour in bed (PLMI) and
      statistical analysis performed to assess possible associations. RESULTS: PLMI
      (mean of two nights) ranged from 0 to 60.3 and 37% of the sample had a PLMI> or
      =5. Men had significantly higher PLMIs than females (P=0.003) but PLMI was not
      correlated with age. There was a modest but significant correlation between
      subjectively reported restless leg severity and PLMI (r=0.238; P=0.003), but none
      with reported sleepiness. CONCLUSIONS: This actigraphy technique is a practical
      and reliable tool for community studies. A large proportion of this community
      sample, particularly men, had PLMs. PLMI was not correlated with age or Epworth
      Sleepiness Score.

PMID- 14592144
TI  - Restless legs complaint in African-American and Caucasian hemodialysis patients.
AB  - OBJECTIVES: To compare the prevalence of Restless Legs Syndrome (RLS) symptoms in
      older African-American and Caucasian chronic renal failure patients undergoing
      maintenance hemodialysis (HD). BACKGROUND: Few data are available about the
      prevalence of RLS in racial groups, although it has been suggested that the
      African-American population is at lower risk relative to the Caucasian
      population. Chronic renal failure patients on HD are known to be at increased
      risk for RLS. METHODS: In-person interviews with 308 chronic renal failure
      patients aged 60-87 living in Georgia being treated by in-center HD. RESULTS:
      More Caucasian patients than African-American patients reported experiencing RLS
      symptoms during the past 6 months (68 vs. 48%; P=0.0006). In a logistic
      regression analysis, African-American patients' reduced risk of RLS complaint was
      independent of patients' age, gender, education, body mass index (BMI), months on
      dialysis, diabetes as primary diagnosis, presence of cardiovascular comorbidity,
      and average number of weekly hours of HD. CONCLUSIONS: Our data suggested a lower
      prevalence of RLS among older African-American than among older Caucasian
      patients on chronic HD. Further study is needed to determine whether this
      difference also occurs in idiopathic RLS and/or at different ages. The
      possibility of systematic reporting differences related to race should also be
      considered.

PMID- 14592145
TI  - The sleep EEG's microstructure in depression: alterations of the phase relations
      between EEG rhythms during REM and NREM sleep.
AB  - OBJECTIVE: We investigated the microstructure of sleep electroencephalograms
      (EEGs) of 13 unmedicated depressive inpatients and 13 healthy controls matched in
      sex and age, hypothesizing that depressives depict an alteration of certain EEG
      oscillations across the night. METHODS: We digitized the sleep EEGs with a
      sampling rate of 100 Hz (bipolar derivation C(z)-P(z), 1440 single sweeps; 2048
      data points each), calculated the time course of delta (1-3.5 Hz), theta (3.5-7.5
      Hz), alpha (7.5-15 Hz), and beta (15-35 Hz) activity over the night, and
      determined the correlation coefficients of these different EEG rhythms separately
      for rapid eye movement (REM) and non-rapid eye movement (NREM) sleep. RESULTS:
      For both groups we detected a clear difference between REM and NREM sleep cycles
      at certain frequency bands. The most impressive changes occurred for the
      delta/beta and theta/beta correlations, which change their signs between NREM
      (negatively correlated) and REM (positively correlated) sleep cycles. Following
      an analysis of variance model with repeated measurement design, a statistically
      significant group effect (P=0.024) between depressives and controls was
      observable during NREM sleep for the delta/beta (P=0.010) and theta/beta
      (P=0.018) interactions. CONCLUSION: We detected alterations of certain sleep EEG
      oscillations during the NREM sleep cycle, where the delta/beta as well as the
      theta/beta activities were higher (negatively) compared to healthy controls.
      Together with previous investigations on the influence of antidepressants on the
      microstructure of sleep EEGs, this is another hint that the NREM sleep cycle
      plays a major role in depression.

PMID- 14592146
TI  - Work and rest sleep schedules of 227 European truck drivers.
AB  - OBJECTIVE: To investigate the sleep-wake behavior and performance of a random
      sample of European truck drivers. METHODS: The drivers completed a questionnaire
      concerning sleep-wake habits and disorders experienced during the previous 3
      months. In addition, they were asked to complete a sleep and travel log that
      included their usual work and rest periods during the previous two days. They
      answered questions concerning working conditions and reported their caffeine and
      nicotine intake during their trips. RESULTS: A total of 227 drivers, mean age
      37.7+/- 8.4 years (96.2% acceptance rate), participated in the study. The drivers
      were found to have a fairly consistent total nocturnal sleep time during their
      work week, but on the last night at home prior to the new work week there was an
      abrupt earlier wake-up time associated with a decrease in nocturnal sleep time.
      Of the drivers, 12.3% had slept less than 6 h in the 24 h previous to the
      interview and 17.1% had been awake more than 16 h. CONCLUSIONS: Shifting sleep
      schedules between work and rest periods can generate long episodes of
      wakefulness. This type of sleep deprivation is rarely investigated. Its is
      usually not taken into consideration when creating work schedules, but affects
      the performance of drivers. Unsuspected shifts occur at the onset of a new
      workweek. Sleep hygiene education for professional drivers is still far from
      perfect.

PMID- 14592147
TI  - Sleep bruxism related to obstructive sleep apnea: the effect of continuous
      positive airway pressure.
AB  - Several studies have reported that sleep bruxism rarely occurs in isolation.
      Recently, in an epidemiological study of sleep bruxism and risk factors in the
      general population, it was found that among the associated sleep symptoms and
      disorders obstructive sleep apnea (OSA) was the highest risk factor for tooth
      grinding during sleep. The purpose of this report was to evaluate the effect of
      continuous positive airway pressure (CPAP) on sleep bruxism in a patient with
      both severe OSA and sleep tooth grinding. Two polysomnographic (PSG) recordings
      were carried out. The first showed 67 events of sounded tooth grinding, most of
      them appearing as an arousal response at the end of apnea/hypopnea events in both
      the supine and lateral postures. During the CPAP titration night most breathing
      abnormalities were eliminated and a complete eradication of the tooth grinding
      events was observed. The results of this study suggest that when sleep bruxism is
      related to apnea/hypopneas, the successful treatment of these breathing
      abnormalities may eliminate bruxism during sleep.

PMID- 14592148
TI  - Periodic arousals or periodic limb movements during sleep?
AB  - Periodic limb movements during sleep (PLMS), frequently found in polysomnograms,
      are often accompanied by arousals. The relationship is not clear, however,
      because PLMS can occur before, after or simultaneous to the electromyographic
      (EMG) activation. We describe the case of a patient who presents PLMS during two
      of three consecutive recording nights, and periodic arousals without motor
      activation on the other night. We conclude that, at least in some patients with a
      periodic limb movement disorder, there exists an underlying arousal disorder that
      produces periodic activation and deactivation of the cerebral cortex.

PMID- 14592149
TI  - Hypocretin (orexin) and melatonin values in a narcoleptic-like sleep disorder
      after pinealectomy.
AB  - Narcolepsy secondary to other neurologic processes has been recently associated
      with hypocretin (orexin) deficiency. We present a patient who developed a
      narcoleptic-like sleep disorder after receiving treatment for a choroid plexus
      carcinoma of the pineal gland. She underwent a pinealectomy, chemotherapy, and
      radiation treatment. The primary features of this condition were excessive
      daytime sleepiness, sleep paralysis and hypnagogic hallucinations. Increased
      percentage of rapid eye movement (REM) sleep and sleep onset REM periods were
      seen during the multiple sleep latency test. Circadian rhythmicity was preserved
      for melatonin and cortisol. She was negative for human leukocyte antigen
      DQB1*0602 and had a detectable cerebrospinal fluid hypocretin level (518 pg/ml).
      We emphasize that the narcoleptic-like disorder likely resulted from the surgical
      intervention or radiation therapy. Her symptoms are caused by an unknown
      mechanism unrelated to hypocretin depletion which merits more research.

PMID- 14592150
TI  - Sleep-related eating disorder in fraternal twins.
AB  - Sleep-related eating disorder (SRED) is characterized by nocturnal partial
      arousals associated with compulsive consumption of food and altered levels of
      consciousness. Reports of an increased incidence of SRED in relatives of affected
      individuals suggest a genetic predisposition. We report a woman with SRED whose
      fraternal twin sister and father are also affected.

PMID- 14592151
TI  - Polysomnographic sleep effects of fluoxetine and nefazodone on a seasonal
      affective disorder patient.
AB  - This reported person met DSM-III-R criteria for seasonal affective disorder. In
      successive years she had two treatments with fluoxetine and one with nefazodone.
      Every year regular polysomnographic monitoring was carried out during the
      critical initial 8 weeks of treatment. The results indicate that on both
      occasions fluoxetine decreased the patient's sleep quality. Nefazodone had no
      sleep disturbing effects and on withdrawal no relapse has been seen for 3 years.

PMID- 14592156
TI  - The importance of sleep medicine consultation for diagnosis of REM sleep behavior
      disorder in most patients with Parkinson's disease.

PMID- 14592157
TI  - Obstructive sleep apnea represents a risk factor for carotid arteries
      atherosclerosis.

PMID- 14592153
TI  - Re: Silber MH, Krahn LE, Olson EJ. Diagnosing narcolepsy: validity and
      reliability of new diagnostic criteria. Sleep Med. 2002 Mar;3(2):109-13.

PMID- 14592159
TI  - Family history study of the restless legs syndrome.
AB  - BACKGROUND: Although there is a relatively high rate of occurrence of sporadic
      cases of restless legs syndrome (RLS), the systematic study of family history of
      RLS in populations of RLS patients has been very limited. The objective of the
      present study was to determine the risk of RLS for first- and second-degree
      relatives of a population of primary RLS patients not selected for the number of
      affected relatives in their families and to obtain an estimate of the degree of
      genetic involvement in RLS. METHODS: Consecutively consenting patients from two
      different sites who met the criteria for RLS completed a worksheet that asked
      them to indicate their current age, the date of their earliest RLS symptoms, and
      the names and RLS status of all of their first- and second-degree relatives.
      Controls with no clinical history of RLS also completed the worksheet. RESULTS:
      First- and second-degree relatives of patients with RLS had a significantly
      greater risk of RLS than the first- (P<0.001) and second-degree relatives
      (P<0.003) of controls. The risk of RLS was found to be greater for first-degree
      relatives of early-onset, rather than late-onset, RLS probands (P<0.001).
      CONCLUSIONS: This study provides a complete systematic examination of the risk of
      RLS among relatives of RLS probands and controls using the same assessment
      methodology. Although the results are consistent with a genetic etiology for RLS,
      they do not support the presence of one simple, Mendelian-inherited major gene in
      most RLS families.

PMID- 14592160
TI  - The genetics of restless legs syndrome.

PMID- 14592161
TI  - Epidemiology of restless legs syndrome.

PMID- 14592162
TI  - Circadian aspects in the pathophysiology of the restless legs syndrome.
AB  - Several pieces of evidence suggest that a dopaminergic dysfunction might play a
      key role in the pathophysiology of restless legs syndrome (RLS), including the
      therapeutic effects of dopaminergic drugs and the results of several positron
      emission tomography and single photon emission computed tomography studies.
      However, RLS symptoms display a distinct circadian pattern, with an increase of
      both sensorial and motor symptoms in the evening and at night. Although the
      latter could also be caused by homeostatic mechanisms such as a linkage to the
      previous amount of wakefulness, several studies performed over the last few years
      under semiconstant, routine conditions have suggested the existence of a 'true'
      circadian mechanism modulating the severity of RLS symptoms across the day-night
      cycle. Thus, both periodic leg movements of sleep and restlessness show a maximal
      severity in timely coincidence with the falling phase of the core temperature
      circadian cycle. The present article reviews the evidence showing circadian
      oscillation of dopaminergic function and postulates that the amplitude of
      circadian rhythm of dopaminergic function is increased in RLS, with a
      hypofunction at night.

PMID- 14592163
TI  - Restless legs syndrome augmentation and pramipexole treatment.
AB  - OBJECTIVE: To evaluate in an open-label clinical series the occurrence of
      restless legs syndrome (RLS) augmentation in 60 consecutive RLS patients treated
      with pramipexole (PPX) for at least 6 months. BACKGROUND: In patients with
      restless legs syndrome (RLS), augmentation is most commonly seen with long-term
      use of levodopa and pergolide. METHOD: Open-label clinical series in 60
      consecutive RLS patients treated with PPX for at least 6 months. RESULTS:
      Augmentation was observed in five patients (8.3%) after 4-15 weeks of treatment.
      Augmentation occurred more frequently in patients with secondary RLS (4/21) than
      in those with idiopathic RLS (1/39). CONCLUSIONS: Augmentation is unrelated to
      either severity of RLS or doses of PPX. There is a very low optimal therapeutic
      dose of PPX (0.25 mg/day) in most RLS patients (66%).

PMID- 14592164
TI  - Periodic limb movements in sleep: to treat or not to treat?
AB  - BACKGROUND: Approximately 50% of our patients with sleep disturbances have
      periodic limb movements in sleep (PLMS). We have found that a high PLMS index is
      not correlated with the severity of symptoms on the Epworth Sleepiness Scale or
      response to pharmacologic therapy for restless legs syndrome (RLS)/PLMS. We
      hypothesized that differences in rhythm of contraction, predominance of periodic
      leg movements (PLMs) in different sleep stages, or PLM interval might distinguish
      responders from nonresponders. METHODS: We analyzed the hypnograms of 20
      consecutive patients with PLMS, noting the number of PLMs and the PLM intervals
      in different sleep stages, the PLMS index, and the percentage of PLMs that led to
      arousals. RESULTS: We distinguished two groups of patients. The 13 patients in
      group A had a PLM arousal percentage of 10.9+/-5% (mean+/-SD), compared with
      41.9+/-9% for the seven patients in group B. Group B had a lower PLMS index.
      Group A showed little variance in PLM intervals and experienced more delta sleep.
      CONCLUSIONS: PLMS index was not correlated with arousals. A strict rhythm of
      contractions was associated with fewer arousals and better quality of sleep. This
      subgroup may not benefit substantially from specific RLS/PLMS therapy.

PMID- 14592165
TI  - Motor pattern of periodic limb movements in sleep in idiopathic RLS patients.
AB  - OBJECTIVE: Periodic limb movements in sleep (PLMS) are recurrent sleep-related
      movements that often occur in association with restless legs syndrome (RLS). The
      purpose of the present study was to examine the pathophysiology of PLMS in
      patients with idiopathic RLS. METHODS: Ten patients with idiopathic RLS who were
      medication-free or who had withdrawn from medication at least 2 weeks prior to
      the study underwent an extensive neurophysiological investigation that included
      nocturnal video-polysomnographic recording (VPSG), EMG recording, and the
      Multiple Sleep Latency Test (MSLT). Sleep efficiency and PLMS index were
      calculated during VPSG. RESULTS: All patients had an increased PLMS index,
      decreased sleep efficiency, and a pathological MSLT score. Leg muscles were the
      first to be activated, often with alternation of side, and no constant
      recruitment pattern could be found from one episode of PLMS to another, even in
      the same patient. No ordinate caudal or rostral spread of the EMG activity was
      observed. CONCLUSIONS: The results suggest that there are different, independent,
      and unsynchronized generators for PLMS. The direct participation of the cerebral
      cortex in the origin of PLMS is unlikely, suggesting that abnormal spinal cord
      hyperexcitability may act as the primary cause of PLMS, triggered by unidentified
      sleep-related factors.

PMID- 14592166
TI  - EEG mapping, psychometric, and polysomnographic studies in restless legs syndrome
      (RLS) and periodic limb movement disorder (PLMD) patients as compared with normal
      controls.
AB  - OBJECTIVES: Investigation of daytime brain function, psychopathology, and
      objective and subjective sleep and awakening quality in restless legs syndrome
      (RLS) and periodic limb movement disorder (PLMD). METHODS: Thirty-three RLS and
      26 PLMD patients free of psychotropic drugs were studied as compared with age-
      and sex-matched normal controls, utilizing electroencephalographic (EEG) mapping
      and clinical evaluations by the Zung Self-Rating Depression (SDS) and Anxiety
      Scale (SAS), the Quality of Life Index, the Pittsburgh Sleep Quality Index
      (PSQI), and the Epworth Sleepiness Scale. In a subsample of 12 RLS patients, 12
      PLMD patients, and 12 controls, objective and subjective sleep and awakening
      quality were evaluated in two sleep laboratory nights (adaptation and baseline
      night). RESULTS: Scores of the PSQI, SDS, and SAS were found increased in both
      patient groups; RLS patients showed reduced quality of life, while in the PLMD
      group daytime sleepiness was increased. EEG mapping demonstrated findings
      characteristic of major depression in RLS patients and of generalized anxiety
      disorder in PLMD patients. Polysomnography showed a significant deterioration of
      sleep efficiency only for RLS patients, while nocturnal awakenings were increased
      in both patient groups. Concerning sleep architecture, both groups exhibited
      increased S1 and stage shifts and decreased S2, while only PLMD patients showed
      an increase in S4. The PLM/(h TST), the PLM/(h wake) and the PLMS-arousal index
      were significantly increased in both patient groups as compared with controls.
      Subjective sleep and awakening quality and thymopsychic measures were
      deteriorated in RLS. Morning mental performance and fine motor activity were
      deteriorated in both groups, reaction time only in RLS, numerical memory and
      attention variability only in PLMD. CONCLUSION: EEG mapping revealed
      neurophysiological correlates of depression and anxiety in RLS and PLMD,
      respectively, which were confirmed by self-ratings of symptoms.

PMID- 14592167
TI  - Modulation of normal and pathologic motoneuron activity during sleep: insights
      from the neurology clinic, Parkinson's disease, and comments on parkinsonian
      related sleepiness.

PMID- 14592168
TI  - Restless legs syndrome (RLS), Parkinson's disease, and sustained dopaminergic
      therapy for RLS.

PMID- 14592169
TI  - Sleep-disordered breathing, sleepiness, and insulin resistance: is the latter a
      consequence, a pathogenetic factor, or both?

PMID- 14592170
TI  - An examination of thought control strategies employed by acute and chronic
      insomniacs.
AB  - STUDY OBJECTIVES: Theoretical accounts of the progression of insomnia from acute
      to chronic are lacking. A framework is proposed and tested to examine differences
      in cognitive coping styles between acute and chronic insomniacs and the relation
      of cognitive processing and sleep hygiene to causal attributions of insomnia.
      METHOD: In a cross-sectional design, the relationship among sleep disturbance,
      causal attributions and various psychological and behavioural variables was
      examined in a convenience sample of acute and chronic insomniacs from the general
      population (N=308). RESULTS: Negative appraisals and the cognitive coping styles
      'Worry' and 'Punishment' were found to be associated with both acute and chronic
      insomnia, whereas 'Distraction' as a cognitive coping strategy significantly
      reduced reports of chronic insomnia. The results are discussed in relation to
      multi-level interventions and future directions in theory, research and
      application.

PMID- 14592171
TI  - The role of obesity in the increased prevalence of obstructive sleep apnea
      syndrome in patients with polycystic ovarian syndrome.
AB  - OBJECTIVES: To determine the prevalence of obstructive sleep apnea syndrome
      (OSAS) in a population of premenopausal women with polycystic ovarian syndrome
      (PCOS) and to study the impact of obesity on the increased prevalence of OSAS in
      this population. METHODS: Twenty-three premenopausal women with definite PCOS,
      and no prior diagnosis of a sleep disorder, were recruited from gynecology
      clinics. An investigator interviewed them, for symptoms of excessive sleepiness,
      their body mass index (BMI) was calculated, and they underwent overnight
      polysomnography. RESULTS: Sixteen of 23 (69.6%) met criteria for OSAS. Five were
      treated with continuous positive airway pressure. Confidence interval was 47.7
      84.5%. An increased respiratory disturbance index (RDI) did not correlate with
      higher BMI. CONCLUSIONS: OSAS is significantly more prevalent in this population
      than in a population of obese women. There was no correlation between obesity and
      severity of the OSAS. Obesity is not the cause of this increased prevalence of
      OSAS in a population of women with PCOS.

PMID- 14592172
TI  - ESS dot com.
AB  - BACKGROUND: The Internet is a rich but unregulated source of information, and no
      studies have evaluated sleep medicine content designed for patient or public use.
      OBJECTIVE: To examine how the Epworth Sleepiness Scale is presented on the World
      Wide Web. METHODS: We searched the web with eight search engines, in November
      2000, for the terms 'ESS' or 'Epworth Sleepiness Scale' and examined every site
      that listed the full ESS. RESULTS: The 91 sites were sponsored by academic
      institutions (n=11), private medical groups (34), corporations (21), and web
      information services (25). No information on interpretation of ESS results was
      given by 24 (26%) of the sites; 37 (41%) of the sites stated that a score greater
      than 8, 9, 10, 11, or 12 merits consultation with a clinician. Few sites
      mentioned that insufficient sleep and depression are among the most common causes
      of excessive sleepiness, or that the meaning and value of the ESS are somewhat
      controversial. CONCLUSION: The ESS is widely available on web sites designed for
      public use, but information that would allow appropriate interpretation of
      results is often lacking, misleading, or incomplete.

PMID- 14592173
TI  - Neonatal EEG-sleep disruption mimicking hypoxic-ischemic encephalopathy after
      intrapartum asphyxia.
AB  - OBJECTIVES: EEG-sleep organization of asphyxiated and non-asphyxiated full-term
      neonates was compared during the first 3 days after birth. BACKGROUND: Aggressive
      fetal and neonatal resuscitative efforts have reduced the severe expression of
      the neonatal brain disorder termed hypoxic-ischemic encephalopathy. Neonates may
      alternatively express altered EEG-sleep organization over the first days of life
      after asphyxia which may mimic mild or moderate hypoxic-ischemic encephalopathy.
      None of ten asphyxiated infants had EEG-confirmed seizures or pharmacologically
      induced encephalopathies. All asphyxiated infants expressed fetal distress on
      fetal heart monitoring prior to delivery, and required neonatal resuscitation, as
      reflected in depressed 1, 5, and 10 min Apgar scores. Moderate to severe
      metabolic acidosis was also documented at birth in the asphyxiated group. All ten
      asphyxiated infants displayed either hyperalertness/irritability or
      somnolence/lethargy during the first 24 h after birth, suggesting mild to
      moderate post-asphyxial encephalopathy. Twenty-two 1 h 21-channel EEG polygraphic
      studies were obtained from the first through third days of life on nine
      asphyxiated infants and scored for EEG-sleep states. Studies on 23 non
      asphyxiated newborns were also obtained between 1 and 3 days of life and scored
      for EEG-sleep state. EEG-sleep states were assigned to every minute of each
      record by visual analyses, without knowledge of the presence or absence of
      asphyxia. Comparisons of active, quiet, and indeterminate sleep percentages
      between neonatal groups were performed. Nested MANOVA was used which took into
      account multiple observations per child in the asphyxiated group. RESULTS: The
      percent of active sleep was 44.7% (+/-14.7), the percent of quiet sleep was 38.7%
      (+/-14.3), and the percent of indeterminate sleep was 13.3% (+/-11.4) in the non
      asphyxiated group. The percent of active sleep was 18.9% (+/-18.5), the percent
      of quiet sleep was 46.5% (+/-21.1), and the percent of indeterminate sleep was
      33.4% (+/-19.7) in the asphyxiated group. A significant decrease in active sleep
      (F=39.5, P<0.0001), and significant increases in quiet sleep (F=4.6, P<0.05) and
      indeterminate sleep (F=21.5, P<0.0005) were noted in the asphyxiated group.
      Shorter active sleep bout lengths were noted (F=21.8, P<0.001), while the quiet
      sleep bout lengths remained unchanged for the asphyxiated group. CONCLUSIONS: An
      increased percentage of quiet sleep and indeterminate sleep at the expense of
      decreased active sleep reflects postnatal brain adaptation to asphyxia in infants
      despite the absence of overt clinical or electrographic evidence of hypoxic
      ischemic encephalopathy. Brain adaptation in newborns after acute asphyxial
      stress may be expressed as altered sleep organization, despite clinical signs
      which may masquerade as mild to moderate post-asphyxial encephalopathy. EEG-sleep
      studies can assist in a more accurate classification of newborn encephalopathy
      that does not satisfy the criteria for hypoxic-ischemic encephalopathy.

PMID- 14592174
TI  - Prediction of obstructive sleep apnea by OxiFlow in overweight patients.
AB  - OBJECTIVES: The aim of our study was to assess the diagnostic characteristics of
      the OxiFlow (OF) device that combines oximetry with recording of thermistor
      airflow. METHODS: In patients referred to the sleep laboratory of an obesity
      clinic apnea-hypopnea index (AHI, events h(-1)) was calculated both by a full
      night polysomnography (PSG) and OF on a separate night. Fifty-six patients were
      studied, of whom 49 had OSA defined as an AHI> or =15 events h(-1). RESULTS:
      There was an underestimation of AHI by OF when assessed by the Bland-Altman plot.
      Sensitivity (Se), specificity (Sp), positive (PPV) and negative (NPV) predictive
      values for OF-AHI thresholds (10, 15 and 20 events h(-1)), taking PSG as a gold
      standard with a fixed PSG-AHI threshold of 15 events h(-1), were evaluated in two
      groups of patients with intermediate (group A, n=18, OSA prevalence=72.2%) and
      high (group B, n=38, OSA prevalence=94.7%) clinical probability of OSA. Se and
      PPV ranged respectively from 0.77 to 0.85 and from 0.73 to 0.77 (group A); from
      0.74 to 0.97 and from 0.94 to 0.98 (group B). Sp and NPV ranged respectively from
      0.20 to 0.40 and from 0.33 to 0.40 (group A); from 0.50 to 0.83 and from 0.21 to
      0.67 (group B). Likelihood ratios (LRs) for a positive OF result ranged from 1.06
      to 1.28 (group A) and from 1.83 to 4.42 (group B). CONCLUSIONS: We conclude that
      in a population with a high OSA prevalence, we have found a low agreement between
      PSG-AHI and OF-AHI and an underestimation of AHI by OF. The LRs of OF as a
      diagnostic test were of low significance, precluding its usefulness in generating
      significant shifts in pretest to posttest probability of OSA.

PMID- 14592175
TI  - Effect of age on sleep onset time in rotating shift workers.
AB  - BACKGROUND: To determine the relationship between sleep onset time and age in
      rotating shift workers. METHODS: Sleep diaries were used to record the sleeping
      onset time in rotating shift workers. Work shifts were rotated on a weekly basis
      and fell into three periods: morning (06:00-14:00 h), evening (14:00-22:00 h),
      and night (22:00-06:00 h). Work shifts were rotated in the following order:
      night, evening, and morning. One working week consisted of 5 days. The mean age
      of the male shift workers was 40.3 years. RESULTS: A significantly earlier sleep
      onset time was observed in older workers working morning and evening shifts (r=
      0.42 and r=-0.66, respectively), but not when working night shifts (r=-0.10).
      Regardless of age, night-shift workers usually go to sleep after their shift ends
      at 06:00 h. After the evening shift ends at 22:00 h, older workers tend to go to
      sleep earlier than younger workers. CONCLUSIONS: Sleep onset time becomes earlier
      with age in morning- and evening-shift workers. The morning shift starts very
      early, at 06:00 h, so workers must go to sleep very early to obtain an adequate
      amount of sleep. Older workers may go to sleep earlier because of physiological
      (circadian) and/or social factors associated with shift work.

PMID- 14592176
TI  - State dependent excitability changes of spinal flexor reflex in patients with
      restless legs syndrome secondary to chronic renal failure.
AB  - OBJECTIVE: Periodic limb movement in sleep (PLMS) is a common dysfunction of
      motor control during sleep, occurring either in isolation or associated with a
      variety of neurological disorders including restless legs syndrome (RLS).
      Although the PLMS generators have not been established, their occurrence in
      patients with spinal cord injury and their clinical resemblance to the spinal
      cord flexor withdrawal reflex (FR) suggest that PLMS may originate in the
      circuitry that mediates the FR. The significantly increased spinal cord
      excitability noted in primary RLS/PLMS patients may play an important role in the
      pathophysiology of primary RLS. The aim of this study is to establish whether the
      enhanced spinal cord excitability, which is represented by a lower threshold
      and/or greater spatial spread of the FR, is also true for the RLS/PLMS patients
      whose RLS is secondary to chronic renal failure (CRF). METHODS: Twenty patients
      with RLS/PLMS secondary to CRF have been compared with matched controls according
      to the state dependent changes in FR excitability. All patients met the
      diagnostic criteria for RLS and PLMS. They had CRF for 5.2+/-3.5 years, and were
      under the hemodialysis treatment. Twenty healthy, age and sex matched subjects
      were tested as controls. The electrophysiological testing of the FR was performed
      during wakefulness (9:30-10:30 p.m.) and sleep (beginning of stage II, the first
      sleep cycle). RESULTS: A significant increase in FR excitability was found in
      RLS/PLMS patients with CRF. This abnormality was prominent during sleep, which
      was also true for the primary RLS. CONCLUSIONS: Our results suggest that similar
      neuronal pathways are involved in primary and secondary RLS/PLMS patients. Our
      results also support that RLS/PLMS and FR share a common spinal mechanism.

PMID- 14592177
TI  - Excessive daytime sleepiness: an unusual presentation of myotonic dystrophy.
AB  - Two middle-aged women presented with excessive daytime sleepiness. Examination
      revealed features of myotonic dystrophy with a positive family history. Sleep
      studies revealed frequent awakenings, central apnoeas with significant oxygen
      desaturation.

PMID- 14592178
TI  - Eye movements in REM sleep could be controlled by the same conjugate system while
      awake.
AB  - We describe the impairment of eye movements during REM sleep in a patient with
      internuclear ophthalmoplegia. A 75-year-old woman, complaining of acute unsteady
      gait and diplopia, was diagnosed to have right medial longitudinal fasciculus
      (MLF) syndrome with limited adduction of the right eye. Overnight polysomnography
      revealed the same impairment of right adductive ocular movement during REM sleep.
      Our findings suggest that the MLF mediates lateral conjugation of eye movements
      during REM sleep as well as voluntary lateral conjugate eye movements during
      wakefulness.

PMID- 14592179
TI  - Remitting REM sleep behavior disorder as the initial sign of multiple sclerosis.
AB  - We report a case of a 25-year-old woman presenting with a 6 month history of REM
      sleep behavior disorder (RBD), confirmed by video-polysomnography. A brain MRI
      disclosed multiple cerebral periventricular and pontine non-gadolinium-enhancing
      hyperintensities and CSF isoelectric focusing showed oligoclonal bands,
      consistent with a diagnosis of probable multiple sclerosis (MS). RBD episodes
      disappeared after ACTH treatment, but clinical relapses and MRI follow-up
      confirmed the diagnosis of MS. Although RBD has been described in association
      with MS, it has not been reported as a heralding sign, nor related to MS
      brainstem lesion. Our case emphasizes the value of RBD as a clinical tell-tale
      sign: when isolated RBD appears in a young subject, brain-imaging studies and
      long-term follow-up are warranted.

PMID- 14592180
TI  - Tonsillar lymphoma as a cause of obstructive sleep apnea.
AB  - Infrequently in adults, isolated lesions of the upper airway, larynx, and trachea
      can produce obstructive sleep apnea (OSA). We describe a case of OSA found to be
      caused by tonsillar lymphoma presenting as asymmetric tonsillar hypertrophy.
      Tonsillar lymphoma is rare, but can present as hypertrophied tonsils and/or
      adenopathy and lead to the development of OSA. This report emphasizes the
      importance of a thorough upper airway examination of all patients undergoing
      evaluation for OSA.

PMID- 14592182
TI  - Do dopaminergic agents increase the daytime sleep propensity? Article reviewed:
      Effect of ropinirole on sleep onset. A randomized, placebo-controlled study in
      healthy volunteers.

PMID- 14592183
TI  - Sleep apnea association with hypercoagulability and venous thromboembolism.
      Article reviewed: Obstructive sleep apnea and venous thromboembolism.

PMID- 14592184
TI  - Elevated plasma C-reactive protein and increased cardiovascular/cerebrovascular
      risk in sleep apnea patients. Article reviewed: Elevated C-reactive protein in
      patients with obstructive sleep apnea (a brief rapid communication).

PMID- 14592185
TI  - Definitions of respiratory events in sleep-disordered breathing.

PMID- 14592187
TI  - Hot questions about the incidence of narcolepsy.

PMID- 14592190
TI  - Through the looking glass, the unrecognized tragedies of obstructive sleep apnea.

PMID- 14592189
TI  - How knowledge of cyclic alternating pattern improves continuous positive airway
      pressure titration in the management of sleep-disordered breathing.

PMID- 14592191
TI  - Review of receptor agonist and antagonist studies relevant to the opiate system
      in restless legs syndrome.
AB  - BACKGROUND AND PURPOSE: Therapeutic studies of the opioids in restless legs
      syndrome (RLS) are reviewed. PATIENTS AND METHODS: Opioids appear to be a good
      short and long-term treatment for RLS as shown in open-label, double-blind and
      long-term follow-up studies. However, the number of studies is more limited than
      for other therapeutic modalities in RLS such as dopaminergic agents. Furthermore,
      the one long-term study on the therapeutic effect of opioids on RLS published in
      full paper form is retrospective; prospective long-term studies are needed.
      RESULTS: Little addiction and tolerance were noted in any of the studies. Sleep
      apnea was not induced or exacerbated in short-term studies, but this was not the
      case in the long-term study. We have recommended that RLS patients treated with
      chronic opioid therapy be monitored clinically for the development of sleep
      apnea. Studies consistently show that the opiate receptor blocker naloxone
      reverses the improvement in RLS induced by the opioids, implicating the
      endogenous opiate system with its endorphins and enkephalins in the pathogenesis
      of RLS. Studies are mostly consistent in showing that naloxone does not worsen
      RLS symptoms in patients not treated with opioids. This result may be related to
      the differential ability of naloxone to antagonize exogenous opioids as opposed
      to endogenous opioids at the site of the opiate receptor. Naloxone does not block
      the therapeutic effect of dopaminergic agents on RLS symptoms, but dopamine
      receptor blockers do block the therapeutic effects of opioids on RLS symptoms.
      This suggests that the endogenous opioids act upon dopamine systems to improve
      the symptoms of RLS. Some of these receptor blocking studies are blinded and, in
      some cases, the results are dramatic. However, with one exception, there were
      limited numbers of patients studied with receptor blocking agents. CONCLUSION:
      The results of such studies therefore need further verification. In addition,
      future studies should focus on other methodologies, such as opiate receptor PET
      scanning, that might further implicate the endogenous opiate system in the
      pathogenesis of RLS.

PMID- 14592192
TI  - Sleep duration and mortality: The effect of short or long sleep duration on
      cardiovascular and all-cause mortality in working men and women.
AB  - BACKGROUND: There is evidence to suggest that insufficient sleep may have an
      adverse effect on physical and psychological health. Previous studies have
      reported that when adjusting for major risk factors for cardiovascular disease
      and a number of demographic and social variables, sleeping 7-8 h each night is
      associated with lower mortality. These studies, however, have excluded any
      consideration of stress, which is known to be related to a number of behavioural
      risk factors for disease and, like sleep, may influence neurochemical, hormonal
      and immunological functioning. METHODS: This study revisits the associations
      between sleep duration, cardiovascular disease risk factors and mortality, taking
      into account the perceived stress of individuals. The data come from a cohort of
      working Scottish men and women recruited between 1970 and 1973; approximately
      half of the cohort was screened for a second time, 4-7 years after the baseline
      examination. RESULTS: For both men and women, higher self-perceived stress was
      associated with a reduction in the hours of sleep reported. The pattern of
      mortality from all causes and the pattern of mortality from cardiovascular
      disease were consistent for both men and women. When sleep was measured on one
      occasion only, the risk of dying was reduced for men sleeping more than 8 h in
      every 24 h compared with those sleeping 7-8 h over the same period. This was
      after adjustment had been made for age, marital status, social class,
      cardiovascular risk factors and stress. The risk of dying was increased for women
      sleeping less than 7 h in every 24 h compared with those sleeping 7-8 h over the
      same period, after similar adjustments. When the data from the 1st and 2nd
      screening were considered longitudinally, both men and women who reported that
      they slept less than 7 h on both occasions that they were questioned, had a
      greater risk of dying from any cause than those who had reported sleeping 7-8 h
      at both screenings, after adjusting for age, marital status, social class and
      stress. CONCLUSIONS: Short sleep over a prolonged period may be associated with
      an increased risk of mortality: men and women who reported sleeping fewer than 7
      h in 24 on two occasions between 4 and 7 years apart, had greater risk of dying
      from any cause over a 25 year period than those who reported sleeping 7-8 h on
      both occasions that they were questioned.

PMID- 14592193
TI  - Cyclic alternating pattern and positive airway pressure titration.
AB  - OBJECTIVE: To demonstrate that stability of the upper airway during continuous
      positive airway pressure (CPAP) titration is influenced by the microstructure of
      sleep as defined by the cyclic alternating pattern (CAP). METHODS: Retrospective
      review of 12 CPAP titration records. The patterns of flow-limitation during CPAP
      at subtherapeutic pressures were characterized as 'stable' (persistent and non
      progressive inspiratory flow limitation) or 'unstable' (progressive increase in
      inspiratory flow-limitation terminating in an arousal), and continuous periods of
      at least 10 min were identified. Sleep stage scoring by both conventional
      Rechtshaffen and Kales criteria and the CAP were done. The relationship between
      flow type and CAP was determined. Responses to an increase in applied pressure on
      flow-limitation were noted. RESULTS: There were a total of 50 periods fulfilling
      the above criteria, totaling 1113 min of titration time. Thirty periods (757 min,
      68% of total) showed a stable flow-limitation pattern. A total of 29/30 periods
      showing a stable flow pattern during sleep was scored as non-CAP, and only a
      single 18-min period of stable flow was scored as CAP. A total of 19/20 periods
      showing an unstable flow pattern was in sleep with CAP characteristics, the
      exception being a single 14-min period where unstable flow was noted in non-CAP.
      Flow-limitation was stable and non-progressive or absent during non-CAP, even at
      less than optimal pressures. This was noted irrespective of the presence or
      absence of delta sleep as scored by conventional criteria. Pressure increases
      during non-CAP, when the profile of the inspiratory flow was flattened, never
      resulted in a discernable change in the flow profile, while at least two-thirds
      of pressure increments during CAP periods improved flow. CONCLUSIONS: The
      microstructure of sleep as determined by CAP and non-CAP have practical
      implications for manual pressure titration algorithms and research on upper
      airway physiology during sleep. The appearance of a period of non-CAP,
      irrespective of conventionally scored delta sleep, may falsely suggest that the
      CPAP is optimal or close to it. Large increases in non-CAP that may be seen
      during a titration night can reduce the window of opportunity for titration.
      Increases in CPAP should be avoided in non-CAP.

PMID- 14592194
TI  - Amnestic sleep-related eating disorder associated with zolpidem.
AB  - OBJECTIVE: To describe the association of amnestic nocturnal eating behavior with
      use of zolpidem for insomnia. BACKGROUND: Sleep-related eating disorder is
      increasingly recognized in relationship to other diagnosable sleep disorders.
      Many of these disorders, like restless legs syndrome (RLS), give rise to
      complaints of insomnia. Zolpidem is the most commonly prescribed drug for
      insomnia complaints, and although it has sometimes been associated with side
      effects of transient amnesia and sleep walking, an association with sleep-related
      eating has not been previously emphasized. METHODS: Consecutive case series of
      five patients who were using zolpidem and evaluated with nocturnal eating
      behaviors. RESULTS: We evaluated five patients over 11 months with problematic
      amnestic nocturnal eating associated with zolpidem used for complaints of
      insomnia. All five patients had RLS, three had obstructive sleep apnea syndrome,
      two had sleep walking, and one had psychophysiologic insomnia. With
      discontinuation of zolpidem and effective treatment of their sleep disorders,
      nocturnal eating resolved. CONCLUSIONS: Zolpidem, at least in patients with
      underlying sleep disorders that cause frequent arousals, may cause or augment
      sleep-related eating behavior. This report demonstrates the importance of
      arriving at a specific diagnosis for insomnia complaints, and alerts the sleep
      practitioner to this unusual side effect of zolpidem.

PMID- 14592195
TI  - Dose-response relationship between CPAP compliance and measures of sleep apnea
      severity.
AB  - BACKGROUND: Obstructive sleep apnea is a prevalent condition with serious medical
      and psychosocial consequences. Nasal continuous positive airway pressure (CPAP)
      is the treatment of choice and has been shown to reduce the frequency of
      nocturnal respiratory events, improve sleep architecture, and decrease daytime
      sleepiness. However, little is known about the dose-response relationship between
      CPAP compliance and measures of sleep apnea severity. This study examined the
      relationship between level of CPAP compliance and change in polysomnographic
      measures of sleep apnea severity. METHODS: Twenty-three CPAP-naive OSA patients
      were studied. None had other major medical illnesses or were receiving
      antihypertensive medication. Sleep apnea variables were measured at baseline and
      after 1 week of treatment. Objective CPAP compliance was measured nightly and was
      defined as the average number of hours of use per night. RESULTS: Higher rates of
      CPAP compliance were linearly associated with significant reductions in the
      respiratory disturbance index (R=0.49, P=0.017), the oxygen desaturation index
      (R=0.48, P=0.029), and the arousal index (R=0.51, P=0.016). CONCLUSIONS: These
      data suggest that increased CPAP compliance is linearly associated with
      reductions in sleep apnea severity such that greater reductions in apnea were
      seen with increased CPAP use. It should be noted that all patients were
      reasonably compliant (i.e. >4h CPAP use/night) and that even within this range of
      reasonable compliance, there was a significant benefit with more as opposed to
      less compliance. These findings offer support to the current recommendation that
      CPAP be used during the total time in bed to optimize treatment of
      polysomnographic measures of sleep apnea.

PMID- 14592196
TI  - Increased body mass index (BMI) in male narcoleptic patients, but not in HLA-DR2
      positive healthy male volunteers.
AB  - BACKGROUND: There is growing evidence that hypocretin deficiency plays a pivotal
      role in human narcolepsy. Based on the physiological role of hypocretins in the
      regulation of food intake, one might suspect that narcoleptic patients should
      display reduced energy intake and as a consequence a reduced body weight compared
      to healthy controls. METHODS: The body mass indices (BMIs) of 30 male narcoleptic
      patients were compared with large community-based reference samples. Because it
      is unclear whether increased BMI is an acquired consequence of the disease or a
      genetically determined premorbid feature of narcolepsy, we additionally examined
      the influence of the HLA-DR2 antigen, strongly associated with narcolepsy, on the
      BMI in a group of 117 healthy male volunteers. RESULTS: Narcoleptic patients
      displayed higher age- and gender-specific BMI percentiles compared to a community
      based sample from the German (normal) population. Within the patient sample, BMI
      distribution did not significantly differ between subjects who had previously
      received pharmacological treatment compared to drug-naive patients, or between
      the HLA-DR2 positive and negative healthy subjects. CONCLUSIONS: The results of
      the present study suggest that an increased BMI in narcolepsy is neither
      associated with the HLA-DR2 antigen per se nor with medication, but is more
      likely to be a consequence of disease-associated neuroendocrine abnormalities.

PMID- 14592197
TI  - Sleep disruption in systemic sclerosis (scleroderma) patients: clinical and
      polysomnographic findings.
AB  - BACKGROUND: Progressive systemic sclerosis (SSc) is a connective tissue disease
      characterized by endothelial lesions and fibrosis of the skin and other organs.
      Patients' quality of life and life expectancy are determined by the intensity of
      pulmonary, esophageal, cardiac, and renal involvement. Neurological involvement
      was considered to be rare, but increasing evidence indicates that peripheral and
      autonomic neuropathies commonly occur. Conditions seen with SSc, such as
      pulmonary fibrosis and gastro-esophageal reflux, have the potential to affect
      sleep. No systematic assessment of sleep-related problems associated with this
      disorder has been performed. MATERIAL AND METHODS: An all-night polysomnogram and
      a clinical interview blinded to sleep status were obtained for 27 consecutive SSc
      patients. Sleep data were compared to age adjusted published normative values.
      Correlations were determined for sleep and clinical data. RESULTS: Patients with
      SSc had a reduced sleep efficiency (SE) (mean+/-SD: 82+/-12.3%) and rapid eye
      movement sleep (13.1+/-5.6%) and increased arousal index (26.1+/-13.0) and slow
      wave sleep (25.7+/-9.7%). The periodic leg movement index (PLMI) exceeded 5/h in
      13 patients (48%) and 25/h in seven patients. Six patients had restless legs
      syndrome (RLS). Significant disordered breathing was absent. The RLS patients
      showed a greater arousal index than all other patients. PLMI was correlated with
      SE for RLS but not for non-RLS patients. Esophageal dyskinesia, dyspnea, and RLS
      were significantly associated with poor sleep. CONCLUSION: Patients with SSc have
      significant disturbance of their sleep. Esophageal dyskinesia and dyspnea, which
      are common complications of SSc, were commonly associated with indices of sleep
      disruption. RLS but not sleep apnea appears to have an increased prevalence in
      SSc.

PMID- 14592198
TI  - Pupillometry in clinically sleepy patients.
AB  - OBJECTIVES: Investigators have suggested using pupillometry to assess alertness
      in hypersomnolent patients. In this study we assessed hypersomnolent patients and
      normal volunteers by using pupillometry and examined the usefulness of this
      technique for the diagnosis of pathologic sleepiness in individual patients.
      METHODS: Forty-nine patients were examined by pupillometry and their sleepiness
      was assessed by using the multiple sleep latency test (MSLT). Thirty-three normal
      well-rested volunteers were also examined by pupillometry. The patients were
      classified as having 'mild', 'moderate', or 'severe' sleepiness, based on their
      mean MSLT sleep latency. Several dynamic variables of pupil diameter were
      calculated from the pupillograms and correlated with the mean MSLT sleep latency,
      and were compared between severity groups of patients and the well-rested normal
      subjects. RESULTS: All but two pupillometric variables were significantly
      correlated with sleep latency. All except the same two pupillometric variables of
      the sleepiest group were significantly different from those of normal subjects.
      However, only 51% of patients with mean sleep latencies less than 10 min and 35%
      of patients with mean sleep latencies of less than 5 min could be correctly
      identified by pupillometry. CONCLUSIONS: Pupillometry is clearly associated with
      differences in alertness between groups of patients. However, pupillometric
      assessment cannot substitute for the MSLT in most cases.

PMID- 14592199
TI  - Narcolepsy and psychopathology: is there an association?
AB  - BACKGROUND: It is widely believed that patients with narcolepsy show high rates
      of associated psychiatric disturbance, especially schizophrenia and depression.
      However, surveys have produced conflicting findings and have not addressed the
      potential confounding effects of stimulant drug treatment. METHOD: Forty-five
      patients with narcolepsy attending a sleep disorder clinic and 50 matched normal
      controls underwent structured psychiatric interview. Using a 'lifetime' approach,
      psychiatric symptoms and diagnoses were established for both groups. RESULTS:
      Four of the narcolepsy patients but none of the controls had experienced
      psychotic symptoms. All four patients were taking amphetamines, and the symptoms
      resolved when the dose was lowered or treatment was changed to modafinil. The
      lifetime frequency of various depressive syndromes did not differ significantly
      between the groups. CONCLUSIONS: Contrary to previous claims this study found
      little to suggest that narcolepsy is associated with schizophrenia. Nor, despite
      its serious social and occupational consequences, does narcolepsy appear to be
      associated with an increased frequency of diagnosable depressive disorders.

PMID- 14592200
TI  - Headache complaints in relation to nocturnal oxygen saturation among patients
      with sleep apnea syndrome.
AB  - BACKGROUND: Morning headaches are often ascribed to patients with sleep apnea
      syndrome (SAS) but the etiology of headaches in SAS is unclear. Given the
      relationship between oxygen and other headache syndromes, nocturnal hypoxia might
      be one factor contributing to headaches in SAS. METHODS: All subjects 18-80 years
      of age who were determined to have SAS and who underwent a continuous positive
      airway pressure trial in our sleep laboratory between March 1, 1997 and March 18,
      1998 were considered for inclusion. Subjects were grouped according to whether
      they endorsed that waking with headaches is a problem for them. Polysomnography
      and standardized questionnaires were used to test the main hypothesis that
      patients with SAS and headaches would spend more time at lower oxyhemoglobin
      levels than those SAS patients without headache. RESULTS: Headache and non
      headache patients did not differ in the percentage of time spent with an oxygen
      saturation less than 90%, either in total sleep time or in rapid eye movement
      sleep (REM). The headache patients were more likely to be female and spend a
      lower percentage of time in REM sleep. The REM sleep difference was not accounted
      for by the use of REM suppressing medications or by depression (as measured by
      the Zung scale). CONCLUSIONS: These data do not support the hypothesis that the
      duration of nocturnal hypoxemia relates to headache complaints in patients with
      SAS. The lower REM sleep percentage and higher variability in REM apnea index
      among the headache patients warrants further investigation.

PMID- 14592201
TI  - Exacerbation of REM sleep behavior disorder by chocolate ingestion: a case
      report.
AB  - REM sleep behavior disorder (RBD) is manifest by loss of normal rapid eye
      movement sleep atonia and the acting out of dreams of often violent content. Both
      idiopathic and secondary forms of RBD exist. We report on chocolate as a possible
      new precipitating agent for RBD and comment on a possible mechanism of action in
      this disorder.

PMID- 14592202
TI  - Did this father's sleep apnea contribute to the inadvertent death of his infant
      son?
AB  - Sleepiness impairs memory and concentration. We report a case of a patient who
      inadvertently left his infant son in a car, having forgotten to drop him off at
      day care. The infant died of heat exposure. There is credible evidence that
      sleepiness from a combination of sleep deprivation and previously undiagnosed
      severe obstructive sleep apnea contributed to this tragedy.

PMID- 14592204
TI  - Article reviewed: Mortality associated with sleep duration and insomnia.

PMID- 14592205
TI  - Article reviewed: Plasma orexin-A is lower in patients with narcolepsy.

PMID- 14592208
TI  - Arousals and anti-arousals.

PMID- 14592209
TI  - Subjective sleep quality in cystic fibrosis.
AB  - OBJECTIVES: To evaluate sleep quality in patients with cystic fibrosis (CF).
      METHODS: The Pittsburgh Sleep Quality Index (PSQI) questionnaire was administered
      to 37 CF patients with moderate to severe lung disease in a clinically stable
      state. Sleep studies were performed concurrently. PSQI scores were correlated
      with results of anthropometric variables, arterial blood gas tensions, lung
      function variables, and polysomnographic variables. Potential differences in
      objective measurements between patients with high and low scores on the PSQI were
      assessed. RESULTS: Thirty-seven patients with CF were studied, aged 27+/-8
      (mean+/-1 SD) years and forced expiratory volume in 1 s (FEV(1)) 36+/-12%
      predicted. The mean PSQI was 5.7+/-4.0. Fourteen of the 37 patients had a high
      PSQI, i.e. >5. Significant correlations between objective variables and both
      component scores and total PSQI were as follows: age and 'subjective sleep
      quality' (r=0.4, P<0.05), age and 'sleep duration' (r=0.3, P<0.05), FEV(1) %
      predicted and 'subjective sleep quality' (r=-0.4, P<0.05), carbon monoxide
      transferred per litre of lung volume (KCO) % predicted and 'daytime dysfunction'
      (r=-0.4, P<0.01), PaCO(2) and 'sleep latency' (r=0.4, P<0.01), arterial carbon
      dioxide tension (PaCO(2)) and 'habitual sleep efficiency' (r=0.3, P<0.05),
      PaCO(2) and total PSQI (r=0.4, P<0.05), absolute minimum sleep oxyhemoglobin
      saturation by pulse oximetry (SpO(2) %) and 'sleep latency' (r=-0.4, P<0.05),
      absolute minimum sleep SpO(2) % and 'sleep duration' (r=-0.4, P<0.05), absolute
      minimum sleep SpO(2) % and total PSQI (r=-0.4, P<0.05) and awake transcutaneous
      CO(2) and 'sleep duration' (r=0.45, P<0.05). Better sleep efficiency (P<0.05) and
      a greater % of rapid eye movement (REM) sleep (P<0.05) were found in those
      patients with a PSQI of < or =5. CONCLUSIONS: A number of CF patients reported
      poor sleep quality. A relationship was shown between subjective sleep quality and
      physiological variables describing disease severity. Better sleep efficiency and
      % REM sleep were seen in patients with low PSQI scores. These results suggest a
      useful role for the PSQI in assessing sleep quality in patients with CF.

PMID- 14592210
TI  - Night-to-night variability in sleep in cystic fibrosis.
AB  - OBJECTIVES: The impact of night-to-night variability (NNV) on polysomnography
      (PSG) has been reported mainly in normal subjects, the elderly and patients with
      obstructive sleep apnea with focus on changes in the apnea/hypopnea index, rather
      than measures of nocturnal oxygenation. There is very limited data on NNV in
      patients with cystic fibrosis (CF). The goal of this study was to assess for
      first-night effect and reliability of PSG measurements on nocturnal oxygenation
      and respiratory disturbance in CF. METHODS: A prospective observational study was
      performed in patients with CF who consented to PSG on two consecutive nights.
      Paired t-tests and intra-class correlation coefficients (ICCs) were calculated
      for repeated measures of sleep stage time, sleep efficiency, arousal indices,
      measures of nocturnal oxygenation, and respiratory events in all sleep stages.
      RESULTS: Thirty-one patients with CF were studied, aged 27+/-8 (mean+/-1 SD)
      years and forced expiratory volume in 1 s (FEV(1)) of 37+/-11% of predicted.
      Relative to the first-night PSG, on the second PSG, we observed the following:
      shorter latency to rapid eye movement (REM) sleep (P<0.001), increased sleep
      efficiency (P<0.01), decreased wake after sleep onset (WASO) time (P<0.01),
      decreased percentage of non-REM time with oxyhemoglobin saturation by pulse
      oximetry (SpO(2))< or =90% (P<0.05), decreased number of central apneas per hour
      (P<0.05) and reduced respiratory rate in stage 2 sleep on night 2 (P<0.05).
      Despite these changes, the ICCs between night 1 and night 2 showed good
      repeatability/reliability for measures of nocturnal oxygenation and indices of
      respiratory disturbance, including the percentage of total sleep time with
      SpO(2)< or =90% (ICC=0.85) and apnea-hypopnea index (ICC=0.75). Likewise, the
      ICCs were extremely high for respiratory rate in stage 2 (ICC=0.94), slow wave
      sleep (ICC=0.97), and REM sleep (ICC=0.96). CONCLUSION: Although a first-night
      effect is seen with sleep efficiency, REM latency, and WASO, a single-night PSG
      in patients with CF yields reliable information on nocturnal oxygenation and
      respiratory disturbance.

PMID- 14592211
TI  - CAP and arousals in the structural development of sleep: an integrative
      perspective.
AB  - OBJECTIVES: It is known that the number of arousals per hour of sleep increases
      linearly across life, while the amount of cyclic alternating pattern (CAP)
      undergoes a u-shaped evolution. The present study aimed at investigating the
      differences, overlaps and age-related distribution of arousals and CAP
      components, i.e. subtypes A1, A2, A3. The relationship between the phase A
      subtypes and the structural organization of sleep was also evaluated. METHODS:
      Forty healthy subjects were examined. Polysomnographic analysis was performed
      according to the scoring rules for sleep stages, CAP and American Sleep Disorders
      Association arousals. RESULTS: Arousals occurred more frequently during CAP (40
      events per hour) than in total sleep time (18 events per hour), non-rapid eye
      movement (NREM) sleep (20 events per hour), and rapid eye movement (REM) sleep
      (12 events per hour). Within CAP, arousals always coincided with a subtype A2 or
      A3. Both arousals and subtypes A2 and A3 showed a similar evolution with relation
      to age (linear positive), and to the amounts of light NREM sleep (linear
      positive) and deep NREM sleep (linear negative). In contrast, subtypes A1 showed
      a u-shaped profile across the life span and appeared closely related (linear
      positive) to the time spent in stages 3 and 4. Almost 90% of arousals occurring
      in NREM sleep were preceded in the previous 3s by a K-complex or a delta burst,
      indicating a topical involvement of slow electroencephalographic (EEG) components
      in the arousal build-up. CONCLUSIONS: Arousals show only one side of the multi
      faceted activation complexes, whereas the three subtypes of CAP provide a graded
      picture of arousal features from the strongest A3 subtypes, showing a prevalence
      of EEG desynchrony, to the weakest A1 phases, which are dominated by EEG
      synchrony and represent the prevalent components of CAP (60% of all the phase A
      subtypes).

PMID- 14592212
TI  - Prevalence of sleep complaints and associated factors in community-dwelling older
      people in Brazil: the Bambui Health and Ageing Study (BHAS).
AB  - BACKGROUND: Population-based studies of insomnia among older people residing in
      communities in developing countries are rare. The objectives of this population
      based study were to determine the prevalence and factors associated with insomnia
      among older adults (60 years and over) living in a Brazilian town with 15,000
      inhabitants (Bambui MG). METHODS: All 1742 residents in this age group were
      selected for a structured interview and blood tests. From these, 1516 (87.0%)
      participated in the study. RESULTS: The prevalence of insomnia was 38.9%, being
      higher among women (45.3%) than among men (28.8%). The use of sleeping pills was
      reported by 380/1513 (25.1%) of the participants; 186 (49.0%) of these complained
      of insomnia, suggesting that their treatment should be reassessed. Factors
      independently associated with insomnia were: female sex (OR=1.78, 95% CI=1.41
      2.24), dissatisfaction with free time arrangements (OR=1.88, 95% CI=1.28-2.77),
      self-rated health as reasonable or bad/very bad (OR=2.02, 95% CI=1.50-2.72 and
      OR=3.12, 95% CI=2.21-4.39, respectively), history of previous medical diagnosis
      of some chronic conditions (OR=1.38, 95% CI=1.10-1.73), inability to perform
      routine activities due to a health problem in the previous 2 weeks (OR=1.54, 95%
      CI=1.10-2.15), and staying in bed in the previous 2 weeks (OR=1.61, 95% CI=1.04
      2.48). CONCLUSIONS: The prevalence of insomnia was high, indicating that this was
      a public health problem for older adults living in the study community. Our
      results emphasize the necessity for further investigations about insomnia among
      older people living in small communities in Brazil and other developing
      countries.

PMID- 14592213
TI  - Determinants of nasal CPAP compliance.
AB  - BACKGROUND: Obstructive sleep apnea is a prevalent condition with potentially
      serious medical and psychosocial consequences. Nasal continuous positive airway
      pressure (CPAP) is the treatment-of-choice and has been shown to reduce the
      frequency of nocturnal respiratory events, improve sleep architecture and
      decrease daytime sleepiness. Patient compliance with CPAP is disappointingly low.
      Previous studies examining determinants of CPAP compliance have limited the
      variables studied to patient (sociodemographic), disease status, and treatment
      variables, with few reliable determinants found. METHODS: The purpose of the
      current study was to investigate the relationship between objectively measured
      CPAP compliance and variables from social cognitive theory (SCT) and the
      transtheoretical model (TM). Scales that measure variables from each model were
      developed and reliability evaluated. The relationship between the SCT and TM
      variables and compliance at 1-month post-CPAP-fitting was prospectively evaluated
      on 51 first-time CPAP users. SCT and TM variables were measured on the day of
      CPAP-fitting, at 1-week post-CPAP-fitting, and at 1-month post-CPAP-fitting.
      RESULTS: SCT variables measured 1-week post-CPAP-fitting (R(2)=0.261, P=0.001)
      and TM variables measured 1-week post-CPAP-fitting (R(2)=0.17, P=0.002) accounted
      for a statistically significant amount of variance in objective CPAP compliance
      measured at 1 month. The decisional balance index (from TM) individually
      accounted for a significant amount of variance in objective CPAP compliance in
      the above analyses. CONCLUSIONS: The ability of these new behavior change scales
      to predict CPAP compliance provides us with a new direction of research to better
      understand factors associated with compliance. The principal advantage of these
      theory-driven and empirically validated scales are that they measure modifiable
      factors that can provide the basis for sound interventions to improve CPAP
      compliance.

PMID- 14592214
TI  - Prediction of the final MSLT result from the results of the first three naps.
AB  - OBJECTIVES: To determine if the mean sleep latency (mSL) and the presence of
      significant sleep onset rapid eye movement periods (SOREMPs) can be predicted
      from the results of the first three naps in selected patients undergoing multiple
      sleep latency test (MSLT). METHODS: Retrospective analysis of a number of MSLTs
      to identify the tests in which the mSL category and the presence of > or =2 naps
      with SOREMPS can be accurately predicted from the sleep latencies (SLs) of and
      SOREMPs in the first three naps. RESULTS: The study included 588 consecutive
      MSLTs performed on 552 patients during a 3-year period. (1) The mSL was normal (>
      or =10 min) for all MSLTs (n=90, 15%) if either (a) the SL was normal in each of
      the first three naps, or (b) SL was 20 min for any two of the first three naps.
      (2) The mSL was low (<5 min) or borderline (> or =5 and <10 min) for 99% MSLTs
      with SL in the low or borderline categories, respectively. (3) The accuracy of
      predicting > or =2 naps with SOREMPs was 100% (normal SL), 96% (borderline SL),
      and 89% (low SL). (4) The mSL category (normal or low) and the presence of > or
      =2 naps with SOREMPs were predicted with 100% accuracy in 23% of all MSLTs.
      CONCLUSIONS: The category of mSL can be predicted with >99% accuracy, if SL is
      normal, borderline, or low in each of the first three naps, or if the patient
      does not sleep in any two of the first three naps. MSLT can probably be shortened
      to three naps in up to 23% to reduce time, labor, discomfort, and cost of the
      test.

PMID- 14592215
TI  - Sawtooth wave density analysis during REM sleep in normal volunteers.
AB  - OBJECTIVE: Sawtooth waves (STW) are a characteristic EEG feature of REM sleep but
      their source and function are unknown. We previously reported stereotypical
      properties of STW at stage REM onset, and alterations in bulbar postpolio
      syndrome. This study analyzes STW features throughout REM, in order to test the
      hypothesis that sawtooth wave activity may be predictable and have a consistent
      relationship across REM periods. METHODS: Twenty polysomnographic recordings were
      scored for occurrence, duration, and frequency of STWs. STW density was
      calculated based on the number of bursts/min REM and duration of STW activity/min
      REM. The density measurements were statistically analyzed to assess for
      differences across REM periods. RESULTS: STW density mean was 0.97 bursts/min REM
      (95% CI [0.85, 1.09]); 6.85 s/min REM (95% CI [5.95, 7.76]). STW frequency range
      was 1.5-5 Hz, mean 2.5 Hz. STWs occurred in bursts with a mean duration of 7 s
      (range 2-26 s). There was a lower density of bursts of STW activity per minute in
      the first REM period compared to the second, third, and fifth cycles.
      CONCLUSIONS: This study reports STW density characteristics throughout REM sleep
      in normal subjects. Our density measurements suggest a difference in STW activity
      between the first REM period and later periods. Analysis of STW and related
      phenomena may increase the understanding of REM sleep mechanisms and may be
      useful to evaluate brainstem function during normal and pathological sleep.

PMID- 14592216
TI  - A comparison of sleep deprivation and narcolepsy in terms of complex cognitive
      performance and subjective sleepiness.
AB  - OBJECTIVES: (i) To expose 'normal sleepers' to a 32-h sleep deprivation protocol
      and evaluate the impact of this deprivation on a complex performance task i.e.
      the paced auditory serial addition test (PASAT). (ii) To compare these sleep
      deprivation performance findings with historical data on the impact of sleepiness
      secondary to narcolepsy on PASAT performance measures. (iii) To investigate the
      recuperative effects of a brief nap period on both sleepiness and PASAT
      performance for the sleep-deprived subjects. (iv) To compare these post-nap
      effects with historical data relating to the impact of napping on both sleepiness
      and PASAT performance for subjects with narcolepsy. BACKGROUND: Previous research
      has demonstrated that sleepiness induced by sleep deprivation in normal sleepers
      may lead to cognitive impairment across a range of performance tasks. Sleepiness
      secondary to narcolepsy has also been noted to impair cognitive function
      especially for complex processing tasks. Direct comparison of the effects of
      sleepiness on performance between non-pathological and pathological sleepiness
      states is confounded, however, by methodological differences in research design
      especially in relation to levels of induced sleepiness and performance task
      selection. The purpose of the current study was to undertake a sleep deprivation
      study that achieved a methodological match with published data evaluating the
      impact of sleepiness on cognitive performance for subjects with narcolepsy. This
      methodological matching allowed for a more precise comparison of the impact of
      sleepiness on performance between non-pathological and pathological sleepiness
      groups. RESULTS: Normal sleepers required a 32-h deprivation protocol to develop
      a subjective level of sleepiness that equated with that identified by subjects
      with narcolepsy. This induced sleepiness in normal sleepers did not result in any
      significant decrement in complex performance, a finding that was in contrast to
      the performance decrement previously found in subjects with narcolepsy with
      equivalent subjective sleepiness ratings. A 20-min nap produced more improvement
      in both arousal and cognitive processing performance for the subjects with
      narcolepsy than for the current sleep-deprivation cohort. CONCLUSION: This study
      identified significant differences in the impact of sleepiness on complex
      performance between non-pathological sleep-deprived subjects and subjects with
      narcolepsy. This paper explores these differences in relation to the potential
      for both quantitative and qualitative differences that exist in the nature of
      sleepiness between non-pathological and pathological sleepiness states.

PMID- 14592217
TI  - DRB1*1502-DQB1*0601-DQA1*0103 and DRB1*04-DQB1*0302 in Jewish hypersomnolent
      patients.
AB  - OBJECTIVES: Narcolepsy is a sleep disorder with a genetic association with the
      haplotype DRB1*1501, DQA1*0102, DQB1*0602. This haplotype has been described in
      different ethnic groups suffering from narcolepsy (Japanese, Caucasian, African
      Americans, Jews). In a recent study we have found the haplotype DRB1*1502,
      DQB1*0601, DQA1*0103 in three patients with hypersomnolence. The similarity of
      this haplotype to the narcoleptic haplotype DRB1*1501, DQB1*0602 and DQA1*0102
      has raised the question of whether this haplotype is a marker for sleepiness, or
      rather indicates a variant of non-cataplectic narcolepsy. This study was
      conducted to further investigate this question. METHODS: HLA-DNA analysis was
      carried out in 20 healthy Jewish patients (age 23.9+/-6.3 years; 13 Ashkenazi,
      seven non-Ashkenazi) who had objective measures of hypersomnolence. All underwent
      whole-night polysomnography, multiple sleep latency test and tissue typing.
      RESULTS: HLA-DNA analysis revealed HLA-DR2 in eight patients of whom five (25%)
      carried the haplotype DRB1*1502, DQB1*0601, DQA1*0103 (vs. 1.4% in the Israeli
      population, P<0.0001). Six patients were diagnosed as non-cataplectic
      narcoleptics. Five of them carried the haplotype DRB1*1502, DQB1*0601, DQA1*0103.
      Forty percent of the patients carried the haplotype DRB1*04, DQB1*0302, which was
      not statistically different from its prevalence in the healthy Israeli population
      (25%). CONCLUSIONS: This is the first report describing the haplotype DRB1*1502,
      DQB1*0601, DQA1*0103 in narcoleptic patients (non-cataplectic). This haplotype is
      close but different from the already known narcoleptic haplotype DRB1*1501,
      DQA1*0102, DQB1*0602. We assume that this haplotype represents a variant of non
      cataplectic narcolepsy rather than association with hypersomnolence. However, in
      order to conclude whether this haplotype is a marker for the lack of cataplexy,
      or represents a variant of non-cataplectic narcolepsy, a larger group of patients
      should be investigated.

PMID- 14592219
TI  - Pergolide-associated 'sleep attacks' in a patient with restless legs syndrome.
AB  - The occurrence of irresistible sleep episodes ('sleep attacks') has been noted in
      patients with Parkinson's syndrome treated with dopa-agonists. This is the first
      report of 'sleep attacks' in a patient with restless legs syndrome in whom
      treatment with pergolide was reduced from 2 to less than 1 mg/day. 'Sleep
      attacks' were accompanied by a reduced mean sleep latency of 5 min and 20 s
      (without sleep onset REM periods) on a multiple sleep latency test. 'Sleep
      attacks' disappeared when pergolide was tapered off and substituted with
      pramipexol. The appearance of 'sleep attacks' as a 'withdrawal' effect of
      pergolide is consistent with a wakefulness-promoting action of postsynaptic
      dopaminergic receptors at higher doses of dopamine agonists.

PMID- 14592218
TI  - The effects of coffee consumption on sleep and melatonin secretion.
AB  - BACKGROUND: In this study we examined the effects of caffeine on sleep quality
      and melatonin secretion. Melatonin is the principal hormone responsible for
      synchronization of sleep. Melatonin secretion is controlled by neurotransmitters
      that can be affected by caffeine. METHODS: In the first part of the study, six
      volunteers drank either decaffeinated or regular coffee in a double-blind fashion
      on one day, and the alternate beverage 7 days later. Sleep parameters were
      assessed by actigraphy. In the second part of the study, the subjects again drank
      either decaffeinated or regular coffee, and they then collected urine every 3h
      for quantitation of 6-sulphoxymelatonin (6-SMT), the main metabolite of melatonin
      in the urine. RESULTS: We found that drinking regular caffeinated coffee,
      compared to decaffeinated coffee, caused a decrease in the total amount of sleep
      and quality of sleep, and an increase in the length of time of sleep induction.
      Caffeinated coffee caused a decrease in 6-SMT excretion throughout the following
      night. CONCLUSIONS: The results of our study confirm the widely held belief that
      coffee consumption interferes with sleep quantity and quality. In addition, we
      found that the consumption of caffeine decreases 6-SMT excretion. Individuals who
      suffer from sleep abnormalities should avoid caffeinated coffee during the
      evening hours.

PMID- 14592220
TI  - Polysomnographic study of sleeplessness and oneiricisms in the alcohol withdrawal
      syndrome.
AB  - We describe a polysomnographic observation of the acute phase of the alcohol
      withdrawal syndrome, characterized by an alteration of the sleep-wake cycle and
      by the absence of non-rapid eye movement sleep. An atypical transitional state
      between rapid eye movement sleep and wake with hallucinations and enacting-dream
      behaviors represented the sole sleep pattern. Analogies of alcohol withdrawal
      syndrome with fatal familial insomnia and Morvan's fibrillary chorea suggest a
      common pathophysiological mechanism in these conditions.

PMID- 14592222
TI  - The first genetic locus mapped for RLS is unlikely to be the last. Article
      reviewed: 'Identification of a major susceptibility locus for restless legs
      syndrome on chromosome 12q'.

PMID- 14592223
TI  - Increased risk of obstructive sleep apnea in obese women with polycystic ovary
      syndrome (a review of two related articles). Articles reviewed: 'Increased
      prevalence of obstructive sleep apnea syndrome in obese women with polycystic
      ovary syndrome' and 'Polycystic ovary syndrome is associated with obstructive
      sleep apnea and daytime sleepiness: role of insulin resistance'.

PMID- 14592224
TI  - Clinical sleep services for children: clinical and administrative considerations.
AB  - Increased recognition of the importance of pediatric sleep medicine, which
      emphasizes the developmental aspects of sleep and incorporates a number of
      clinical sleep disorders unique to children and adolescents, has generated
      considerable interest in expansion of clinical sleep services to meet children's
      specific needs. This article provides a synopsis of the key points regarding
      provision of sleep services to children and adolescents as discussed by a panel
      of pediatric sleep experts at the annual meeting of the Association of
      Professional Sleep Societies in June, 2000. Essential considerations in
      establishing a pediatric sleep practice and future directions are provided.

PMID- 14592225
TI  - Definitions of respiratory events in sleep-disordered breathing.

PMID- 14592226
TI  - Is there a subpopulation of children with growing pains who really have Restless
      Legs Syndrome? A review of the literature.
AB  - Symptoms of Restless Legs Syndrome (RLS) can begin in childhood and persist into
      adulthood. To our knowledge, no one has done a systematic review of the
      literature to determine if the descriptions of 'growing pains' are consistent
      with the diagnosis of childhood RLS. Our group and that of Ekbom have noted that
      childhood onset RLS can be misdiagnosed as 'growing pains'. We therefore reviewed
      the work of seven groups of authors that addressed 'growing pains' as an isolated
      phenomenon in order to determine whether the descriptions of 'growing pains' were
      consistent with the clinical features of RLS. We found no consistent pattern in
      the descriptions even when articular pain was excluded. Thus, it is unlikely that
      all patients with 'growing pains' have RLS and it is likely that 'growing pains'
      is a heterogeneous disorder. The aforementioned authors were not looking for
      features unique to RLS and descriptions of the complete symptom complex of RLS
      are usually lacking. Further complicating the data are problems with methodology,
      e.g. in some studies small children and their parents were asked to
      retrospectively recall remote and infrequent events, and in other studies,
      articular pain was not adequately ruled out. Inconsistent with the hypothesis
      that RLS and 'growing pains' are the same are the high association of 'growing
      pains' with migraine headaches and abdominal pain. However, from this background
      emerge subsets of patients with 'growing pains' that are described as having one,
      some, or all of the following features consistent with the diagnosis of RLS:
      symptoms that are primarily in the legs, the patients rub their legs to get
      relief of the discomfort, the symptoms are worse at night, sleep disturbance is
      present and the discomfort is sometimes accompanied by motor restlessness A non
      painful form of 'growing pains' has even been described. Ekbom and Brenning, a
      contemporary of Ekom, directly addressed the relationship between 'growing pains'
      and RLS. Ekbom felt that 'growing pains' and RLS were probably different since
      'growing pains' disappear after childhood and one of his patients described her
      childhood 'growing pains' as being different from the sensory discomfort of her
      adult onset RLS. However, Brenning showed that RLS-like features in adulthood and
      a previous history of 'growing pains' in childhood occurred far more frequently
      in the parents of children with 'growing pains' than in control parents. More
      work needs to be done on the potential relationship between 'growing pains' and
      RLS.

PMID- 14592227
TI  - A new questionnaire to detect sleep disorders.
AB  - OBJECTIVES: Sleep disorders remain largely undiagnosed in the general population.
      The current study assessed whether the Global Sleep Assessment Questionnaire
      (GSAQ) could: (1), distinguish between sleep disorders (including no sleep
      disorder); (2), be a reliable and valid sleep disorder screener; and (3), serve
      as a practical, user-friendly screening tool for primary care and sleep centers.
      METHODS: Two hundred and twelve adults from five sleep centers and two primary
      care clinics completed the GSAQ and received confirmed diagnoses from a sleep
      specialist. Of the 212 patients, 139 (65.6%) had at least one sleep disorder, 60
      (28.3%) had two or more sleep disorders, and 13 (6.1%) had no confirmed sleep
      disorder. Ninety-one (43%) individuals completed the GSAQ a second time for
      reliability testing. Scores for each sleep disorder including, but not limited
      to, primary insomnia (I), insomnia associated with a mental disorder (IME),
      obstructive sleep apnea (OSA), periodic limb movement (PLM), and parasomnia (P)
      were computed. The sensitivity and specificity were estimated using comprehensive
      clinical diagnosis as the gold standard and mean domain scores as a cutpoint.
      RESULTS: The mean participant age was 45 years, 52% were female. Observed
      frequencies were: 36 (I), 14 (IME), 31 (OSA), 7 (PLM) and 4% (P). Test-retest
      reliability ranged from 0.51 to 0.92. Pearson correlation coefficients suggested
      that the GSAQ discriminated between diagnoses. The sensitivities and
      specificities were 79/57, 83/51, 93/58, 93/52, and 100/49 for I, IME, OSA, PLM,
      and P, respectively. CONCLUSIONS: Our findings suggest that the GSAQ can aid in
      recognizing sleep disorders. Future studies should focus on characterizing its
      predictive values in primary care settings.

PMID- 14592228
TI  - Diagnosing narcolepsy: validity and reliability of new diagnostic criteria.
AB  - BACKGROUND AND PURPOSE: No gold standard currently exists for the diagnosis of
      narcolepsy. Conventional diagnostic criteria are unwieldy and arbitrary. Clearly
      defined criteria for case selection are needed to compare the results of
      different studies. METHODS: We developed new clinical and neurophysiologic
      criteria for narcolepsy using four categories, based on the degree of diagnostic
      certainty. Category A is Definite Narcolepsy, Category B is Probable Narcolepsy
      (Laboratory Supported; two subgroups B1 and B2) and Category C is Probable
      Narcolepsy (Clinical). We assessed the charts of 69 new or established patients
      with narcolepsy seen consecutively in the Mayo Sleep Disorders Center and
      classified them according to our system. The human leucocyte antigen (HLA)
      DQB1*0602 status was determined for each patient as an indirect measure of
      validity. Two investigators independently assessed 30 charts to assess interrater
      reliability. We assessed additional 337 charts of patients with other
      hypersomnolence states to assess the specificity of our definitions. RESULTS:
      Seventy-four percent were positive for HLA DQB1*0602 (including 85% of those with
      cataplexy). Only 33% of those without cataplexy were HLA DQB1*0602 positive. The
      two investigators agreed on the classification of 29/30 patients (0.97
      reliability). None of the 337 additional patients fulfilled criteria for
      narcolepsy, and specifically not for cataplexy. CONCLUSIONS: We conclude that our
      new research diagnostic criteria for narcolepsy possess high interrater
      reliability and appear valid descriptors of the syndrome, based on HLA typing.
      They may be useful in providing consistent criteria to compare different research
      studies.

PMID- 14592229
TI  - Prevalence and consequences of insomnia disorders in the general population of
      Italy.
AB  - OBJECTIVES: To assess the prevalence of insomnia disorders using DSM-IV
      classification, and the consequences of insomnia in the Italian general
      population. METHODS: A representative sample of the Italian general population
      composed of 3970 individuals aged 15 years or older were interviewed by telephone
      using the Sleep-EVAL system (participation rate: 89.4%). Participants were
      interviewed about their sleep habits and sleep disorders. DSM-IV classification
      was used by Sleep-EVAL to determine the sleep disorder diagnosis. RESULTS:
      Insomnia symptoms were reported by 27.6% of the sample. Sleep dissatisfaction was
      found in 10.1% and insomnia disorder diagnoses in 7% of the sample. The use of
      sleep-enhancing medication was reported by 5.7% of the sample. Most of these
      subjects were using anxiolytics. Dissatisfaction with sleep was associated with
      daytime sleepiness. Middle-aged drivers dissatisfied with their sleep were three
      times more likely to have had a road accident in the previous year compared to
      other drivers. However, fewer than 30% of subjects dissatisfied with their sleep
      or with an insomnia disorder diagnosis had consulted a physician about their
      sleep problem. CONCLUSIONS: As in other European and non-European countries,
      insomnia is widespread in Italy. The consequences are important. Appropriate
      recognition and treatment of insomnia should be part of an educational program
      for general practitioners everywhere.

PMID- 14592230
TI  - Prevalence of insomnia and associated socio-demographic factors in a Brazilian
      community: the Bambui study.
AB  - BACKGROUND: Population-based studies of insomnia among adults residing in
      communities in developing countries are rare. The objectives of this population
      based study were to determine the prevalence and factors associated with insomnia
      among adults (18 years and over) living in a Brazilian town with 15,000
      inhabitants (Bambui MG) and to determine how the use of different definitions of
      insomnia affect its prevalence. METHODS: A total of 87.3% of 1221 randomly
      selected individuals aged 18+ participated. Prevalences were estimated based on
      different definitions. To determine the associated characteristics, insomnia was
      defined as a complaint in the last month, occurring at least three times a week,
      causing distress. RESULTS: (1) Prevalence ranged from 12.0 to 76.3%; (2)
      prevalence of insomnia, as defined above, was 35.4%; (3) prevalence among women
      increased with age and was higher than that of men; (4) insomnia was
      independently associated with less education in both sexes, and among females it
      was associated with older age (60+ years). CONCLUSIONS: The prevalence of
      insomnia in Bambui was high, similar to that of urban centers of developed
      countries; this investigation substantiated the importance of operational
      criteria in studies of insomnia.

PMID- 14592231
TI  - Low body stores of iron and restless legs syndrome: a correctable cause of
      insomnia in adolescents and teenagers.
AB  - BACKGROUND: It has been shown that restless legs syndrome (RLS) in adults may be
      linked to abnormalities in iron stores. Whether reduced iron stores play a role
      in children is not clear. METHODS: We evaluated the status of iron stores and
      sleep in three teenagers who presented with severe sleep onset insomnia,
      subjective sleep latency exceeding 60 min and excessive daytime sleepiness.
      RESULTS: The three teenagers were found to have RLS and laboratory evaluation
      confirmed reduced body stores of iron with a low percent iron saturation (mean
      value 9.7%) and a low serum ferritin level (mean value 17 microg/l). None had
      marked anemia. The three patients were treated with oral iron for 4-5 months. As
      a group they had an increase in percent iron saturation (from a mean of 9.7 to
      22.7%) and serum ferritin (from a mean of 17 to 27 microg/l) and a marked
      reduction of the symptoms of RLS, with mean subjective sleep latency decreasing
      from 143 to 23 min, sleep efficiency increasing from 75.7 to 84.0% and the number
      of periodic movements per hour of sleep decreasing from 20.5 to 10.5.
      INTERPRETATION: These findings support the hypothesis that abnormal iron stores
      or metabolism may result in RLS causing insomnia in teenagers. We recommend
      evaluation of iron status including serum iron, total iron binding capacity and
      ferritin levels in teenagers with chronic insomnia of unexplained origin even
      when anemia is mild or absent.

PMID- 14592232
TI  - Pulseoximetry: sufficient to diagnose severe sleep apnea.
AB  - OBJECTIVES: To assess the clinical value of pulseoximetry in the diagnosis of
      sleep apnea when satisfactory agreement with polysomnography is obtained.
      METHODS: This was a prospective clinical study, set in the Department of
      Otorhinolaryngology, Ullevaal University Hospital, Oslo, Norway. One hundred
      consecutive patients were investigated for sleep related breathing disorders. The
      main outcome measurements were: measurement success rate, oxygen desaturation
      thresholds, sensitivity and specificity at apnea-hypopnea-index (AHI) thresholds
      of 5 and 15. RESULTS: Pulseoximetry was successfully performed in 93%. When
      different oxygen desaturation thresholds were calculated, optimal agreement with
      polysomnography was found at a 3% oxygen desaturation level. The sensitivity and
      specificity of diagnosing moderate/severe sleep apnea (AHI above 15) were 0.86
      and 0.88, respectively. The corresponding figures for milder sleep apnea (AHI
      above 5) were 0.91 and 0.67. Good agreement was found between the AHI and the
      oxygen desaturation index (ODI) at the 3% level, with a mean AHI-ODI difference
      of 2.6 (SD, 7.3), a Pearson correlation of 0.95 and a weighted kappa of 0.86. The
      best agreement was found for AHI values below 15, where the estimated AHI-ODI
      difference was only -0.4 (SD, 3.3). CONCLUSIONS: Pulseoximetry is a simple, non
      invasive procedure, which is easy to perform and well suited for outpatient
      registration. When adjusted to polysomnography with high sensitivity of hypopnea
      registrations, an ODI at the 3% level is optimal to diagnose sleep apnea. In
      patients with moderate/severe sleep apnea with AHI values above 15, it is
      sufficient to establish the diagnosis and subsequent treatment. A negative
      pulseoximetry does not rule out sleep disorders; the patients should complete a
      full examination.

PMID- 14592233
TI  - Personality, anxiety and mood traits in patients with sleep-related breathing
      disorders: effect of reduced daytime alertness.
AB  - OBJECTIVE: The etiology of depression and personality disorders in patients with
      sleep-disordered breathing (SDB) is not well defined and it is still unclear if
      they are directly related to the severity of the disease. In this study we test
      the hypothesis as to whether daytime sleepiness largely contributes to appearance
      of mood disorders. METHODS: Sixty patients diagnosed as having snoring (n=16) or
      OSA (n=44) were examined. Daytime sleepiness was assessed by the administration
      of the Epworth Sleepiness Scale (ESS) and by the Maintenance Wakefulness Test
      (MWT). The Hospital Anxiety (HAD-A) and Depression (HAD-D) Scale and the
      Temperament and Character Inventory (TCI) questionnaires were used for
      psychopathological evaluation. RESULTS: The mean HAD-A score was 6.9+/-0.45 and
      the average HAD-D score was 4.6+/-0.48, with no significant difference between
      snorers and OSA patients. Anxiety was present in 16% of cases and depression in
      7%. The HAD-D score was related to the ESS score (R=0.37, P=0.003), the mean
      sleep latency at the MWT (R=-0.34, P=0.04), and the mean low SaO(2), ESS score
      alone explaining the 17% of variance in the HAD-D score. Compared to controls,
      there were no differences in almost all TCI scores, with novelty-seeking
      temperament score higher in patients. No relationships were found between HAD or
      TCI scores and apnea density. CONCLUSIONS: We conclude that among patients
      evaluated for SDB, higher depression scores show an association with reduced
      daytime alertness, which therefore may have important effects on mood.

PMID- 14592234
TI  - The prevalence of sleep disorders in patients with Parkinson's disease. A self
      reported, community-based survey.
AB  - OBJECTIVE: Sleep disruption is common in patients with Parkinson's disease (PD).
      The goal of our survey was to gain insight into the causes of sleep disruption
      and into the prevalence of specific sleep disorders in PD. METHOD: A sleep
      questionnaire was mailed to 400 unselected PD patients. Analysis of the results
      was descriptive. RESULTS AND CONCLUSION: The results of earlier performed surveys
      for sleep disruptive factors in PD were confirmed and a high prevalence of a
      possible rapid eye movement-sleep behavior disorder and restless legs syndrome in
      PD was found.

PMID- 14592235
TI  - Prosthetic therapy in the management of nasopharyngeal stenosis following
      uvulopalatopharyngoplasty for obstructive sleep apnea.

PMID- 14592236
TI  - Sleep and EEG power spectrum in post encephalitis hypersomnia: a case report.
AB  - The nocturnal recordings of breathing, and sleep and daytime multiple sleep
      latency tests over the 5 year follow-up of a patient with post encephalitis
      hypersomnia are presented. EEG power spectrum analysis was performed on the last
      polysomnographic recording, and the results were compared with those obtained for
      a matched control subject. The patient presented initially a hypoventilation
      syndrome controlled by nasal bilevel positive pressure at night. The syndrome
      progressively improved, but daytime sleepiness stayed unchanged with limited help
      from stimulants. Fast Fourier transformation analysis of the last nocturnal
      recording demonstrates a decrease in absolute power for all frequency bands in
      all sleep stages, but a cyclical presence of the NREM/REM.

PMID- 14592237
TI  - Dose response to melatonin treatment for disordered sleep rhythm in a blind
      child.
AB  - We assessed the effectiveness and safety of melatonin in normalizing sleep in a 7
      year-old blind child with a longstanding sleep/wake cycle disorder, using a
      double-masked, randomized treatment trial of placebo, a physiological dose (0.14
      mg) and a supraphysiological dose (2.2 mg) of melatonin. Sleep onset and sleep
      offset were erratic and inappropriately early with placebo and low dose
      melatonin, but improved significantly on high dose melatonin. This report
      confirms that melatonin may be effective in treatment of disordered sleep rhythm
      in blind children, and illustrates a protocol that enables dose adjustment for
      optimal treatment response.

PMID- 14592238
TI  - Technical protocol for the use of esophageal manometry in the diagnosis of sleep
      related breathing disorders.
AB  - A time-tested protocol for intrathoracic pressure monitoring during sleep is
      described. This method of esophageal manometry uses a fluid-filled catheter to
      measure variations in transmitted intrathoracic pressure with respiration.
      Esophageal manometry is an invaluable tool for the sleep specialist in the
      diagnosis of sleep-related breathing disorders, especially for detecting cases of
      upper airway resistance syndrome and for distinguishing subtle central apneas
      from obstructive events. The methods for scoring esophageal pressure, the
      indications and contraindications for esophageal manometry, the use of esophageal
      manometry as the 'gold standard' for the measurement of respiratory effort, and
      directions for future research are also discussed.

PMID- 14592240
TI  - Article reviewed: Familial advanced sleep phase syndrome.

PMID- 14592242
TI  - Article reviewed: REM sleep behavior disorder in sleep-disordered patients with
      versus without Parkinson's disease: is there a need for polysomnography?

PMID- 14592241
TI  - Article reviewed: Sleep-disordered breathing and respiratory failure in acid
      maltase deficiency.

PMID- 14592244
TI  - Atlas, rules, and recording techniques for the scoring of cyclic alternating
      pattern (CAP) in human sleep.

PMID- 14592247
TI  - Preliminary evidence of behavioral and cognitive sequelae of obstructive sleep
      apnea in children.
AB  - OBJECTIVES: To characterize the daytime sequelae of obstructive sleep apnea (OSA)
      in children. BACKGROUND: OSA syndrome is a common disorder in children with
      estimates of prevalence ranging from 1.1 to 2.9%. Numerous studies have
      documented neuropsychological deficits in adults with OSA, although only a few
      preliminary studies have described these problems in children with OSA. METHODS:
      In the present study, otherwise healthy children with OSA (n=28), and a healthy
      age-matched comparison group (n=10) were assessed with standard measures of
      sleep, behavior, and cognitive function. RESULTS: Children with OSA had
      significantly more behavior problems than the healthy comparison group based on
      parents' reports (F=7.29, P<0.005). Children diagnosed with moderate to severe
      OSA had significantly lower scores on a timed cancellation task that assesses
      sustained attention (F=10.0, P<0.01). A significant association was found between
      OSA severity (rho=-86, P<0.01) and measures of verbal ability. CONCLUSIONS: These
      initial findings suggest that there are identifiable daytime sequelae of
      childhood OSA and that it is important to evaluate these daytime disturbances in
      making determinations about intervention.

PMID- 14592248
TI  - Recurrent hyper- and hyposomnia: a new diagnostic entity? Polysomnographic
      findings and a 30-year follow-up.
AB  - OBJECTIVES: This study reports on the sleep evaluation and follow-up of a
      professional woman who, in her 30s and 40s, had a decade of severe episodic
      fluctuations in the length of her sleep (12 vs. 4 h). BACKGROUND: Severe
      psychogenic fluctuations in the duration of sleep have not previously been
      described except in bipolar disorders. METHODS: Psychological and medical history
      and a total of 29 polysomnogram nights are presented, as well as a 30-year follow
      up interview. RESULTS: Long sleep episodes (>10 h) were characterized by
      excessive stage 1 sleep and a stage we called 'very light sleep' (over 50% alpha
      waves mixed with 5-10% delta waves). Long sleeps were also associated with
      hyperphagia and hypersexuality. Short sleeps (<4 h) emphasized delta and REM
      sleep. Sleep normalized spontaneously after about a decade of severe
      fluctuations. CONCLUSIONS: In this patient, the recurrent hypersomnia/hyposomnia
      episodes may have been based mainly on psychiatric factors.

PMID- 14592249
TI  - Sleeping habits in the Austrian population.
AB  - OBJECTIVES: To gain reliable data on sleeping habits and sleep disturbances of
      the Austrian population. BACKGROUND: Exact data on sleeping habits are of
      interest in relation to assessment of sleep disturbance-related illnesses and
      general social processes. METHODS: A prospective, cross-sectional study was
      performed with recruitment of a representative sample of 1049 Austrians (aged 15
      82 years), according to the Federal Statistics population characteristics.
      Interviews were conducted in the households of the participants by specially
      trained interviewers of an institute for empirical research. RESULTS: Men
      consider their quality of sleep to be significantly better than women
      (P=0.00234), and younger persons consider their quality of sleep to be
      significantly better than older persons (P=0.00001). In comparison, women and
      people over the age of 50 report worse subjective sleep quality, worse sleep
      efficiency, more difficulty in falling asleep and sleep maintenance, more apneic
      events, more pathologic limb movements, more daytime dysfunction, and more intake
      of sleeping medication. Other sociodemographic factors influence sleep reports to
      a lesser extent. CONCLUSIONS: Subjectively disturbed sleep (prevalence in the
      total population 24.9%), excessive hypnotic drug intake (prevalence 13.0%), and
      daytime dysfunction (prevalence 17.4%) are a widespread problem, especially in
      women and older people. With increasing life expectancy in Western societies, the
      prevalence of sleep disturbances will increase.

PMID- 14592250
TI  - Comparison of Epworth Sleepiness Scale scores by patients with obstructive sleep
      apnea and their bed partners.
AB  - OBJECTIVES: In some patients with obstructive sleep apnea (OSA), Epworth
      Sleepiness Scale scores (ESS) do not reflect the severity of disease. In many
      cases, bed partners (BPs) report more severe hypersomnia on the part of the
      patient than the patient him/herself. The purpose of this study was to assess the
      agreement between patients and BPs on ESS scores and to compare patients and BPs
      on the correlation between ESS and the severity of OSA. METHODS: ESS scores were
      estimated by patients and their BPs and their scores were compared. The
      correlation between the ESS and the apnea-hypopnea index, arousal index, minimum
      oxygen desaturation, and body mass index of the patient was estimated and
      compared between the patient and BP. RESULTS: ESS scores of the patient and BP
      were similar in their correlation with polysomnographic variables. BPs tended to
      give slightly higher ESS scores than the patient. CONCLUSIONS: ESS scores as
      estimated by BPs of patients with OSA did not correlate more positively with
      polysomnographic variables of OSA severity than scores estimated by affected
      patients.

PMID- 14592251
TI  - Sleep and periodic limb movements in corticobasal degeneration.
AB  - Corticobasal degeneration (CBD) exhibits distinct features of akinesia, the
      'alien limb' sign and cortical myoclonus. We report a 63-year old woman with a
      history of CBD for 18 months who was studied twice using all-night
      polysomnography with an interval of 13 months. Both recordings revealed frequent
      periodic arm and leg movements predominantly during non-REM sleep. To our
      knowledge this has not been described in a patient with CBD so far. Similar to a
      previous report we found REM sleep without atonia (RWA) in all REM episodes.
      However, the patient showed RWA and some non violent movements that fulfilled the
      diagnosis of subclinical REM sleep behavior disorder only in the second
      investigation. These observations may be due to the underlying degenerative
      process that involves not only cortical but also thalamic and brainstem
      structures.

PMID- 14592252
TI  - Effects of pregnancy on mothers' sleep.
AB  - OBJECTIVES: To survey the effects of pregnancy on mothers' sleep. METHODS:
      Mothers were interviewed during and after pregnancy with a series of five
      questionnaires to assess alterations in their sleep. The first questionnaire
      covered the 3 months before becoming pregnant, the next three the trimesters of
      pregnancy and the last the 3 months after delivery. The study was carried out in
      a central hospital and the maternity care units in the nearby rural community.
      Altogether, 325 pregnant women completed all five questionnaires. RESULTS: The
      total amounts of reported sleep and of nocturnal sleep increased significantly
      during the first trimester of pregnancy, began to decrease thereafter and were
      shortest during the 3 months after pregnancy. During late pregnancy expectant
      mothers over 30 years of age reported less sleep than those under 30. During the
      whole pregnancy, but increasingly toward the end of pregnancy, sleep became more
      restless and fragmentary and its subjective quality worsened, due at least partly
      to increased restless legs and nightly awakenings increasing with advancing
      pregnancy. CONCLUSIONS: The subjective quality of sleep is disturbed as early as
      the first trimester of pregnancy, although total sleeping time increases. The
      amount of reported sleep begins to decrease in the second trimester. The
      frequency of reported sleep disturbances, such as restless legs syndrome and
      nocturnal awakenings, is maximum in the third trimester but is about normal
      within 3 months after delivery.

PMID- 14592253
TI  - Scoring variability between polysomnography technologists in different sleep
      laboratories.
AB  - OBJECTIVE: Examine the variability of polysomnography technologists from
      different sleep laboratories regarding scoring of polysomnograms. BACKGROUND:
      Polysomnography is the gold standard to diagnose obstructive sleep apnea-hypopnea
      syndrome. There are criteria to score sleep stages and respiratory events. We
      sought to determine how different technologists would score the same tests using
      their laboratory's criteria. METHODS: Eleven technologists in nine different
      sleep laboratories which used the Oxford Medilog SAC system scored eleven sleep
      studies performed in the Medical University of South Carolina Sleep Disorders
      Laboratory utilizing their respective laboratory's scoring rules. All sleep
      studies were performed for evaluation of obstructive sleep apnea-hypopnea
      syndrome (OSAHS). The scored studies were returned and analyzed for variability.
      RESULTS: Significant variability was present in scoring of both sleep and
      respiratory events with more variability demonstrated in respiratory event
      scoring. In four of the studies, diagnoses based on apnea-hypopnea indices (AHI)
      varied from none to moderate OSAHS depending on which technologist scored the
      study and in one study the diagnosis varied from none to severe OSAHS.
      CONCLUSIONS: Clinicians should be aware that there is tremendous variability
      among polysomnography technologists regarding the scoring of polysomnograms.
      These differences are likely due to different rules used to score events as well
      as differences in the technologist's interpretation of the rules.

PMID- 14592254
TI  - Pergolide restores sleep maintenance but impairs sleep EEG synchronization in
      patients with restless legs syndrome.
AB  - BACKGROUND: The treatment with the long-acting dopamine D1/D2 receptor agonist
      pergolide has been proven as very effective in lowering the frequency of periodic
      leg movements (PLM) in patients with restless legs syndrome (RLS). To further
      investigate the influence of this potent dopaminergic drug on the microstructure
      of rapid eye movement (REM) and non-REM sleep EEG we established a quantitative
      analysis of the EEG data. METHODS: The study group consisted of 15 patients with
      primary RLS (mean age 57.1+/-10.1 years) who were a subgroup of patients within a
      double-blind randomized crossover treatment study with pergolide versus placebo.
      The polysomnographic recordings were analyzed visually and submitted to a
      quantitative EEG analysis (fast Fourier transformation). RESULTS: The pergolide
      treatment induced a significant reduction of the spectral power in the delta
      range (0.78-3.9 Hz; P<0.05; t-test) during SWS, as well as a significant
      reduction of PLMs. In addition, we observed a decrease in the sigma EEG activity
      (12.1-14.8 Hz; P<0.03) during non-REM sleep and stage 2 sleep. The visual sleep
      scoring revealed a significant increase in stage 2 sleep (P<0.005), whereas
      wakefulness was markedly diminished (P<0.001). The REM sleep parameters including
      the EEG power spectrum remained unchanged. CONCLUSIONS: The treatment with
      pergolide markedly improved the sleep quality in RLS patients but did not restore
      SWS including the spectral power in the lower frequencies. Our results suggest
      that the dopamine agonist pergolide interferes with the subcortical mechanisms
      regulating the process of EEG synchronization during non-REM sleep.

PMID- 14592255
TI  - Marital satisfaction of wives of untreated sleep apneic men.
AB  - OBJECTIVES: The purpose of this study was to assess marital satisfaction of the
      wives of untreated sleep apnea patients. DESIGN AND METHODS: A prospective study
      was carried out that compared the marital satisfaction of wives of men with sleep
      apnea to the marital satisfaction of wives of men presenting to a primary care
      physician's office. The study examined three patient groups: 26 wives of men with
      severe sleep apnea, 19 wives of men with mild sleep apnea, and 19 controls from a
      primary care physician's office. Those with other significant medical disorders
      were excluded. Marital satisfaction using the Dyadic Adjustment Scale and a sleep
      behaviors questionnaire was compared between the patient groups. RESULTS: Wives
      of severe and mild apneic men were similar to controls on marital satisfaction
      but differed significantly in satisfaction with husbands' sleep behaviors.
      CONCLUSIONS: Although the presence of sleep apnea in married men has little
      effect on their wives' overall marital satisfaction, it did affect whether they
      slept together or apart. For these patients, the choice to sleep apart may have
      benefited rather than impaired marital satisfaction.

PMID- 14592256
TI  - Disturbed sleep predicts hypnotic self-administration.
AB  - OBJECTIVES: To evaluative whether polysomnographically determined sleep variables
      in a large group of subjects reflecting a wide range of sleep disturbance would
      be predictive of the self-administration of capsules before sleep. METHODS: Sixty
      four healthy men and women with and without insomnia (aged 21-55 years) were
      given an opportunity to self-administer placebo or triazolam (0.25 mg) capsules
      (single-choice method - available capsule or no capsule) before sleep in three
      separate studies. All qualified using the identical criteria based on a standard
      nocturnal polysomnogram. Screening sleep measures then were used to predict
      subsequent placebo and triazolam self-administration. RESULTS: The percent of
      placebo and triazolam choices did not differ between or within the three studies.
      Persons with persistent psychophysiologic insomnia self-administered more
      capsules than persons with sleep state misperception or normals, with the subject
      groups not differing in placebo vs. active drug preference. Screening
      polysomnographic measures predicted percent of capsule choices. The single best
      predictor was the ratio of minutes of stage 3-4 sleep to minutes of wake plus
      stage 1 sleep with R=0.44. The addition of % stage 3-4 sleep, wake before sleep
      and total sleep time increased R to 0.49. On morning mood ratings less ability to
      concentrate and greater fatigue (Profile of Mood States) predicted percent of
      capsule choices with R=0.36. CONCLUSIONS: These results show that the extent of
      sleep disturbance predicts the likelihood of self-administering a capsule before
      sleep regardless of whether it is placebo or active drug.

PMID- 14592257
TI  - Clinical significance of nocturnal oximeter monitoring for detection of sleep
      apnea syndrome in the elderly.
AB  - OBJECTIVES: The sensitivity and specificity of overnight monitoring of arterial
      oxygen saturation (SaO(2)) using an oximeter were evaluated in elderly subjects
      who are being investigated for possible sleep apnea syndrome (SAS). METHODS:
      Seventy-five consecutive elderly subjects with habitual snoring (47 men, 28
      women; mean (+/-SE) age 75.5+/-0.9 years (range 65-94 years)) were studied. The
      SaO(2) was measured with an oximeter and a chart recorder during the night
      immediately before detailed polysomnographic studies. The SaO(2) recordings were
      classified by two observers as positive or negative using a number of significant
      oxyhemoglobin desaturation (SDS) of more than 2, 4, and 6%. The sensitivity of
      the oximeter alone for the recognition of the SAS was calculated as the number of
      true positive SaO(2) records divided by the total number of positive definitive
      (polysomnographic) records. The specificity was defined as the number of true
      negative SaO(2) records divided by the total number of negative definitive
      records. RESULTS: Of the 75 subjects, 24 had moderate SAS (apnea index (AI)>15)
      and 55 had mild to moderate SAS (AI>5). The sensitivity and specificity of the
      dosimeter as a screening test were determined with the two diagnostic thresholds
      of the AI. For AI exceeding 5 or 15, the respective sensitivity by using the
      criterion of SDS of more than 4% was 85.5 or 91.7%, with corresponding
      specificity of 85.0 or 92.2%. CONCLUSIONS: The nocturnal oximeter monitoring
      allows recognition of elderly subjects with a mild to moderate SAS, and 4%
      desaturation of SaO(2) is a candidate index to detect a significant number of
      apneas in elderly SAS patients with an oximeter.

PMID- 14592258
TI  - Excessive fragmentary hypnic myoclonus: clinical and neurophysiological findings.
AB  - BACKGROUND: Brief involuntary sleep-related twitches occurring asymmetrically
      throughout the body define physiologic hypnic fragmentary myoclonus. An abnormal
      intensification of this entity identifies excessive fragmentary hypnic myoclonus
      (EFHM), a 'proposed sleep disorder' in the International Sleep Disorders
      Classification. METHODS: We describe two patients with EFHM, one associated with
      a REM behaviour disorder. RESULTS: EFHM activity was restricted to sleep
      prevailing during NREM sleep stages and the second part of the night. EMG was
      normal and EEG-EMG back-averaging did not show any cortical potentials related to
      the twitches. CONCLUSIONS: EFHM represents a pathological phenomenon which may or
      may not be associated with other sleep disorders. A brainstem generator explains
      its distribution throughout the body and the sleep stages.

PMID- 14592261
TI  - Article reviewed: Chronic 'jet lag' produces temporal lobe atrophy and spatial
      cognitive deficits.

PMID- 14592259
TI  - Gelastic syncope mistaken for cataplexy.
AB  - Laughter is a complex human behavior that has an emotional and a physical
      component. We present a patient who suffered syncope as a result of intense
      laughter, and hypothesize that this is analogous to other types of Valsalva
      induced syncope. We emphasize the clinical characteristics that differentiate
      gelastic syncope from cataplexy.

PMID- 14592262
TI  - Articles reviewed: Does lack of daytime sleepiness relate to benefits of
      continuous positive airway pressure on the consequences of obstructive sleep
      apnea/hypopnea?: design considerations demonstrated by two recent articles.

PMID- 14592263
TI  - Quality of life in obstructive sleep apnea: a systematic review of the
      literature.
AB  - OBJECTIVE: To review the literature on obstructive sleep apnea (OSA) and health
      related quality of life (HRQOL). BACKGROUND: OSA affects nearly one in four men
      and one in ten women aged 30-60 years in the United States. Health consequences
      of OSA can include neuropsychiatric and cardiovascular sequela that disrupt
      professional, family, and social life and negatively impact HRQOL. METHODS: We
      conducted a comprehensive review of the literature on HRQOL and OSA, with special
      attention paid to instruments developed specifically for OSA. RESULTS: Generic
      instruments used to study HRQOL and OSA include: Medical Outcomes Study Short
      Form-36, Nottingham Health Profile, Sickness Impact Profile, Functional
      Limitations Profile, EuroQol, and Munich Life Quality Dimension List. Specific
      instruments include: Calgary Sleep Apnea Quality of Life Instrument, Functional
      Outcomes of Sleep Questionnaire, OSA Patient Oriented Severity Index, the OSA-18,
      and Cohen's pediatric OSA surgery quality of life questionnaire. CONCLUSIONS: OSA
      patients have impaired HRQOL when compared with healthy age- and gender-matched
      controls. Treatment with continuous positive airway pressure appears to improve
      HRQOL. Other treatment modalities have not been rigorously studied. In addition,
      more data are needed from preference-based measures that allow conversion to
      utility scores, which can be used to calculate quality-adjusted life years and
      cost-effectiveness ratios.

PMID- 14592264
TI  - Psychometric comparisons of the standard and abbreviated DBAS-10 versions of the
      dysfunctional beliefs and attitudes about sleep questionnaire.
AB  - OBJECTIVE: To evaluate the psychometric properties of the DBAS-10, a recently
      proposed abbreviated version of the Dysfunctional Beliefs and Attitudes About
      Sleep Scale (DBAS). POPULATION: Two hundred and eleven (69 normal sleepers; 142
      insomnia suffers) middle-aged and older adults (age 40-79 years) drawn from two
      separate cohorts of research volunteers. METHOD: Volunteers in the first cohort
      (69 normal sleepers; 69 insomnia sufferers) completed the full DBAS on one
      occasion. Volunteers in the second cohort (73 insomnia sufferers) completed the
      full DBAS prior to treatment and at multiple subsequent time points to assess
      treatment-related changes. A series of statistical tests were conducted with one
      or both cohorts to investigate the comparability of the DBAS-10 and full DBAS,
      the internal consistency of each instrument, the factor structure of the DBAS-10,
      and the validity of this instrument. RESULTS: Statistical findings showed that
      the DBAS-10 correlated highly with the full DBAS, had respectable internal
      consistency, effectively discriminated normal sleepers from insomnia sufferers,
      and detected cognitive changes resulting specifically from CBT intervention.
      Although factor analysis empirically identified three conceptually meaningful
      DBAS-10 subscales, the subscale structure varied somewhat from previous factor
      analytic findings with this instrument. CONCLUSIONS: The DBAS-10 generally
      appears to have very acceptable psychometric properties although subscales
      previously proposed for this instrument may vary across research populations.
      Nonetheless, results encourage the use of this instrument in studies concerned
      with the nature and treatment of sleep-disruptive cognitions.

PMID- 14592265
TI  - Clinical prediction of periodic leg movements during sleep in children.
AB  - OBJECTIVE: To assess the utility of several symptoms and a questionnaire-based
      scale in the identification of children with periodic leg movements during sleep
      (PLMS). BACKGROUND: PLMS may have important consequences in some children, but
      the extent to which a diagnosis can be established by clinical history is
      unknown. METHODS: Subjects were patients aged 2-18 years who underwent
      polysomnography to assess for sleep-disordered breathing (SDB). Parents completed
      a Pediatric Sleep Questionnaire which contained items under consideration for
      inclusion in the desired scale. RESULTS: Subjects (n=113) had a mean age of 9.8+/
      4.0 (SD) and 73 (65%) were male; 59 (52%) had SDB and 29 (26%) had five or more
      PLMS per hour of sleep (PLMI> or =5). Severity of SDB was not different among
      those with and without PLMI> or =5. Yes/no responses to several question-items-
      about restless legs, growing pains, leaving the bed at night, waking more than
      twice per night, waking feeling unrefreshed, and morning headaches--showed some
      association with PLMI> or =5 and were combined into a composite PLMS score
      artificially weighted toward the first two items. The PLMS score averaged 0.40+/
      0.31 and ranged from 0.0 to 1.0; a 1 SD increase was associated with PLMI> or =5
      (odds ratio=1.87, 95% confidence interval (1.15, 3.13), P=0.014) after adjustment
      for age, sex, and SDB severity. Sensitivity of a PLMS score>0.33 for PLMI> or =5
      was 0.79, specificity was 0.56, positive predictive value was 0.38, and negative
      predictive value was 0.89. Internal consistency was reasonable (Cronbach's
      alpha=0.71), as was test-retest reliability (rho=0.62, P=0.0026, n=21 separate
      subjects). CONCLUSIONS: Restless legs, growing pains, sleep-maintenance insomnia,
      unrefreshing sleep, and morning headaches show moderate associations with
      polysomnographically-defined PLMS, but several other symptoms do not. These
      results require confirmation but suggest that clinical assessment and the PLMS
      score may be helpful but far from definitive.

PMID- 14592267
TI  - Hypercoagulability in patients with obstructive sleep apnea.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) has been linked to cardiovascular
      complications such as stroke and myocardial infarction. Previous studies
      demonstrate that OSA patients show elevated fibrinogen levels and increased
      platelet aggregation that are reversed with 1 night of nasal continuous positive
      airway pressure treatment (NCPAP). Questioning overall coagulability in OSA, we
      examined whole blood coagulability in 11 chronically NCPAP treated OSA subjects,
      22 previously untreated OSA subjects, and in 16 of these after 1 night of NCPAP
      treatment. PATIENTS AND METHODS: During full polysomnography, subjects from each
      group had blood drawn prior to bedtime (21:00 h) and upon waking in the morning
      (07:00 h). RESULTS: Untreated OSA patients had faster P.M. clotting times than
      chronically treated OSA patients (3.33+/-0.31 versus 6.12+/- 0.66 min, P<0.05 by
      ANOVA). A.M. values showed similar results (4.31+/- 0.34 min versus 7.08+/-0.52
      min, P<0.05 by ANOVA) for the respective groups. One overnight treatment with
      nasal CPAP did not produce a significant change in A.M. whole blood coagulability
      (4.35 +/-0.43 to 5.31+/-0.53 min; n=16; P=0.1) in 16 treated subjects.
      CONCLUSIONS: These data indicate a relationship between obstructive sleep apnea
      and blood hypercoagulability status that appears to be reversed by chronic NCPAP
      treatment. These data suggest that NCPAP might protect against the development of
      cardiovascular complications in OSA patients.

PMID- 14592266
TI  - Long-term follow-up of sleep disordered breathing in older adults.
AB  - OBJECTIVE: The current study was designed to determine whether, with increasing
      age, sleep apnea improves, becomes worse, or stays the same. BACKGROUND: There is
      a high prevalence of sleep disordered breathing (SDB) in older adults, but little
      is known about longitudinal changes. This study followed older adults to examine
      the natural history of SDB. METHODS: Subjects were randomly selected community
      dwelling elderly (n=427). A subset of subjects was studied approximately every 2
      years over an 18-year period. Overnight sleep recordings and sleep questionnaires
      were completed at each time point. RESULTS: Multiple linear regression showed
      that three variables were associated with change in respiratory disturbance index
      (RDI):body mass index (BMI) at initial visit (P=0.001), change in BMI (P=0.02),
      and a consistent self-report of high blood pressure (P=0.005). RDI increase was
      associated with BMI increase and presence of self-reported high blood pressure.
      CONCLUSIONS: The changes in RDI that occurred were associated only with changes
      in BMI and were independent of age. This underscores the importance of managing
      weight for older adults, particularly those with hypertension.

PMID- 14592268
TI  - Tonic and phasic inhibition indices are constant among nights: new indices for
      evaluating the degree of the two types of motor inhibition during REM sleep.
AB  - BACKGROUND: Tonic inhibition index (TII) and phasic inhibition index (PII) were
      proposed as indices for evaluating the degree of two types of motor inhibition
      activity during rapid eye movement (REM) sleep. METHODS: In the present study,
      therefore, six healthy men underwent two consecutive all-night polysomnography,
      and reproducibility of TII and PII was evaluated. RESULTS: TII was 0.85+/-0.07
      (mean+/-SD) on the first night and 0.88+/-0.08 on the second; and PII was 3.4+/
      2.1 on the first night and 4.9+/-1.8 on the second. Neither TII nor PII was
      significantly different between the two nights. CONCLUSION: One night sleep study
      is considered sufficient for using TII and PII as a tool for evaluating motor
      inhibition activity during REM sleep in adults.

PMID- 14592269
TI  - Severe, childhood-onset, idiopathic, life-long insomnia responding selectively to
      opiate therapy: case report with 19 year follow-up.
AB  - BACKGROUND: Idiopathic (primary) insomnia can be difficult to treat; only two
      prior cases responsive to opiate therapy have been reported. A case is now
      presented of severe, idiopathic, childhood-onset, familial insomnia, with
      increased libido, absence of psychopathology, tardive emergence of restless legs
      syndrome (RLS), and selective response to opiate therapy. CASE REPORT: A 39-year
      old woman was referred in 1981 by her physician who had discovered 3 years
      earlier that propoxyphene treatment of migraines also controlled her chronic
      insomnia. She had experienced severe insomnia since childhood, and during early
      adulthood the insomnia intensified, as she would sleep 0-3 h nightly and never
      napped. Daily generalized motor restlessness resulted in her frequently walking
      around the house while feeling exhausted. The quality of her life was
      considerably compromised by her insomnia, motor restlessness, and by an increased
      libido that was present since puberty and that was only partially relieved by
      having sex repeatedly with her husband. RESULTS: Nightly opiate therapy for 19
      years has controlled the insomnia, motor restlessness, and excessive libido
      without affecting her normal libido. The insomnia had not responded to treatment
      with >25 agents covering >10 pharmacologic categories. During her first
      (unmedicated) polysomnographic (PSG) study in 1981, she slept 0 min while
      spending 436 min in bed. In 1984, four consecutive PSG studies were conducted in
      a design that confirmed the efficacy of propoxyphene therapy of her insomnia. In
      1990, an ambulatory PSG revealed two runs of EEG rhythmic paroxysmal activity
      arising from sleep and wakefulness, without clinical correlate. Neurologic
      history was negative for seizures, but positive for complete right carotid artery
      occlusion and three transient ischemic attacks. At age 55 years, typical RLS
      emerged that was controlled with levodopa therapy, and a concurrent relapse of
      insomnia was controlled with oxycodone replacing propoxyphene. CONCLUSIONS:
      Nightly opiate therapy of severe idiopathic (primary) insomnia can remain
      effective during very long-term clinical follow-up. Guidelines are provided for
      when to consider such an unusual treatment in other cases of severe, chronic
      insomnia.

PMID- 14592270
TI  - Atlas, rules, and recording techniques for the scoring of cyclic alternating
      pattern (CAP) in human sleep.

PMID- 14592273
TI  - Article reviewed: Distribution of road accidents in policemen on shift-work on
      Italian highways: the contributing role of sleepiness.

PMID- 14592272
TI  - Article reviewed: Restless Legs Syndrome: a clinical study in general Chilean
      population and in uremic patients.

PMID- 14592275
TI  - Insomnia sensitivity.

PMID- 14592276
TI  - Morning headaches in patients with sleep disorders.

PMID- 14592277
TI  - Computational neuroanatomy in sleep-disordered breathing and related disorders.

PMID- 14592278
TI  - How to use the nasal pressure in clinical practice.

PMID- 14592279
TI  - Morning headaches in patients with sleep disorders: a systematic polysomnographic
      study.
AB  - OBJECTIVES: Patients with sleep disorders suffer more often from headache after
      awakening than healthy subjects. However, it still is a matter of controversy
      whether this applies only to patients with sleep apnea syndrome (SAS) or also to
      patients with other diagnoses of sleep disorders. METHODS: We asked all patients
      in our sleep laboratory about the frequency of past headaches and also
      ascertained the occurrence of morning headaches after awakening in the sleep
      laboratory. Polysomnographic recordings from nights before morning headache were
      compared with nights without following headache. Four hundred and thirty-two
      patients with sleep disorders (age range 18-86 years, 37% women) and 30 healthy
      subjects (age range 24-55 years, 27% women) participated in this prospective
      study. RESULTS: The reported frequency of past headaches and the frequency of
      morning headache in the sleep laboratory were significantly increased in patients
      with SAS and other sleep disorders compared with healthy subjects. The occurrence
      of morning headache in the sleep laboratory was associated polysomnographically
      with a decrease in total sleep time, sleep efficiency and amount of rapid eye
      movement sleep and with an increase in the wake-time during the preceding night.
      CONCLUSIONS: We conclude that morning headaches in patients with sleep disorders
      might be associated with particular disturbances of the preceding night's sleep.
      We speculate that dysregulation in anatomically identical central regions
      modulating sleep and nociception might be relevant to morning headache, rather
      than one particular sleep disorder such as SAS.

PMID- 14592280
TI  - Effects of modafinil on sustained attention performance and quality of life in
      OSA patients with residual sleepiness while being treated with nCPAP.
AB  - BACKGROUND: Some patients with obstructive sleep apnea/hypopnea syndrome (OSA/HS)
      who are regular users of nasal continuous positive airway pressure (nCPAP)
      therapy continue to experience daytime sleepiness that impairs performance and
      quality of life. A randomized, double-blind, placebo-controlled, parallel-group
      study was conducted to determine the effect of modafinil on sustained attention
      performance and functional quality of life in OSA/HS patients with residual
      daytime sleepiness, who were regular users of nCPAP therapy. METHODS: Seventy
      seven patients received modafinil (200 mg/day, week 1; 400 mg/day, weeks 2-4) and
      80 patients received matching placebo once daily for 4 weeks. Sustained attention
      performance on the psychomotor vigilance task (PVT) and functional status and
      quality of life using the Functional Outcomes of Sleep Questionnaire (FOSQ) were
      measured. RESULTS: The frequency of lapses of attention during PVT performance
      was significantly decreased, and both the median and slowest reaction times were
      significantly improved in patients receiving nCPAP plus modafinil compared with
      those receiving nCPAP plus placebo (P=0.010 for the number of lapses
      [transformed], P=0.023 for the median reaction time, and P=0.014 for the
      reciprocal of the 10% slowest reaction times). Treatment with nCPAP plus
      modafinil significantly improved the FOSQ total score (weeks 1 and 4), the
      vigilance subscale score (weeks 1 and 4), and the activity level subscale score
      (week 4) compared with treatment with nCPAP plus placebo (all P<0.05).
      CONCLUSIONS: Consistent with previous results for objective and subjective
      measures of sleepiness, modafinil used adjunctively improved performance on a
      test of behavioral alertness and reduced functional impairments in patients with
      OSA/HS who were regular users of nCPAP therapy but still experiencing sleepiness.

PMID- 14592281
TI  - Oxygen administration improves the serum level of nitric oxide metabolites in
      patients with obstructive sleep apnea syndrome.
AB  - OBJECTIVES AND BACKGROUND: Nocturnal apnea and hypoxia are implicated in the
      pathogenesis of pulmonary and systemic hypertension in obstructive sleep apnea
      syndrome (OSAS). We have hypothesized that vasodilating factors including nitric
      oxide (NO) are affected by nocturnal apnea and hypoxia in patients with OSAS.
      METHOD: We examined the serum level of NO production in 24 patients with OSAS
      (mean age 54.2+/-7.9 years) and 24 age-matched control subjects (53.4+/-8.1
      years) and tested the effects of oxygen administration on the production of NO in
      the patients. RESULTS: The serum level of nitrite/nitrates (NO(x)), which are
      stable metabolites of NO, was lower in patients with OSAS than in control
      subjects. Administration of 1-2 l/min of oxygen during night increased the
      patients' NO(x) level from 35.6+/-7.3 to 57.8+/-11.6 microM. Compressed air
      administration did not affect the NO(x) level in the patients. CONCLUSION: These
      results indicate that systemic NO production is impaired in OSAS patients,
      possibly due to nocturnal hypoxia.

PMID- 14592282
TI  - Approaches to staging sleep in polysomnographic studies with epileptic activity.
AB  - BACKGROUND: The Standardized Sleep Manual of Rechtschaffen and Kales is well
      established and reliable in scoring the majority of polysomnograms (PSGs)
      encountered in clinical practice. In patients with epilepsy, however, abnormal
      brain activity may confound the interpretation of sleep waveforms. Our goal is to
      identify features that are problematic in analyzing sleep stages in patients with
      epilepsy and to offer approaches to score these PSGs. METHODS: Ninety eight PSGs
      from 43 patients with epilepsy were scored using Rechtschaffen and Kales
      guidelines. Features interfering with sleep staging were noted. RESULTS: In
      scoring polysomnograms (PSGs) of patients with epilepsy we noted epileptic
      seizures, interictal epileptiform discharges (IEDs) and abnormal EEG background
      to be features of epilepsy that compromised sleep scoring. Overall, 48% of the
      studies in our sample contained one or more of these epileptic features to the
      extent that sleep scoring by standard criteria was compromised. Approaches for
      staging sleep in the setting of these abnormalities are outlined. CONCLUSIONS:
      The Rechtschaffen and Kales method of sleep scoring is useful in staging the
      majority of PSGs of patients with epilepsy. However, we advocate some
      modifications because the abnormal electrical activity of epilepsy may interfere
      with accurate scoring of sleep waveforms. These approaches to scoring PSGs of
      patients with epilepsy will require empirical testing.

PMID- 14592283
TI  - Scoring polysomnography respiratory events: the utility of nasal pressure and oro
      nasal thermal sensor recordings.
AB  - OBJECTIVE: To evaluate the clinical utility of nasal cannula/pressure (NP) and
      oro-nasal thermal sensor (Th) recordings, alone and in combination for scoring
      respiratory events during routine diagnostic polysomnography (PSG). BACKGROUND:
      The use of Th devices to measure airflow during PSG is not recommended because Th
      are insensitive to airflow changes other then complete airflow cessation. It has
      been suggested that NP recording is a better measure of airflow and can also
      detect increased upper airway resistance during PSG. METHODS: Thirty consecutive
      PSG's were examined using 13 standard channels including Th and NP recordings.
      Respiratory events were scored separately utilizing NP+Th, Th alone and NP alone
      in a blinded fashion using modified AASM criteria. Respiratory events were time
      matched to within 5 s for each of the recording methods. RESULTS: NP+Th detected
      more events than Th alone (P<0.0001); NP+Th detected more events than NP alone
      (P<0.0001) and NP alone detected more events than Th alone (P<0.0001). For AHI
      >50, NP alone and Th alone each detected 90% of matched NP+Th events. However,
      for AHI <50, NP alone detects 54% and Th alone detects 42% (P<0.005) of matched
      NP+Th events. For AHI >50, NP alone scored 97% of matched Th alone scored
      respiratory events, and Th alone scored 94% of NP alone scored respiratory events
      (P>0.05). However, for AHI<50, NP alone scored 90% of matched Th alone scored
      respiratory events, whereas Th alone scored 62% of matched NP alone scored events
      (P<0.0001). CONCLUSIONS: In severe sleep disordered breathing (AHI >50), NP+Th,
      NP alone and Th alone have similar ability to detect respiratory events. When AHI
      <50, NP+Th appears better for detecting respiratory events than NP or Th alone.
      If only one measure of airflow is used, NP detects more events than Th.

PMID- 14592284
TI  - The psychological aspects of patients with delayed sleep phase syndrome (DSPS).
AB  - OBJECTIVE: The current study attempts to define the psychological features of
      patients with delayed sleep-phase syndrome (DSPS). METHOD: We administered the
      Yatabe-Guilford test (Y-G test), Minnesota Multiphasic Personality Inventory
      (MMPI), Picture-Frustration study (P-F study) and Rorschach test to two groups,
      one of patients with DSPS (case group) and the other of people without
      psychiatric symptoms or insomnia (control group). RESULTS: Overall, the results
      of the tests indicate that patients with DSPS showed emotional features such as
      nervousness, depression and lack of control of emotional expression. Specific
      personality traits included introspection, defensiveness, aspiration for
      intellectual attainment with compulsivity, overly abstract thinking, unawareness
      of impulsivity to immediate gratification, perseverance and reduced cognitive
      ability. In addition, the patients with DSPS showed psychopathological features
      similar to those of neurosis, hypochondriasis, depression, conversion hysteria
      and psychopathic deviate. CONCLUSIONS: There seems to exist a definite
      psychological profile for patients with DSPS. (1) an excessive defense mechanism
      that increases nervousness and develops neurosis; (2) a high level of
      intellectual aspiration with compulsivity that makes the patients feel self
      defeated, powerless and disappointed; (3) a tendency to egocentric emotion,
      inhibition and perseverance. These characteristics may worsen social withdrawal,
      causing a loss of social cues in synchronizing their circadian rhythm. Thus, the
      phase shift becomes more difficult and a vicious circle is constituted.

PMID- 14592285
TI  - Assessment of a wrist-worn device in the detection of obstructive sleep apnea.
AB  - OBJECTIVE: To assess the accuracy of a wrist-worn device (Watch_PAT100) to
      diagnose obstructive sleep apnea (OSA). METHODS: Thirty adult subjects with and
      without suspected OSA simultaneously had a standard in-laboratory polysomnogram
      (PSG) and wore the Watch_PAT100 during a full-night recording. PSG sleep and
      respiratory events were scored according to standard criteria. Watch_PAT data
      were analyzed with an automated computerized algorithm which calculated the
      frequency of respiratory events per hour of actigraphy measured sleep using a
      combination of peripheral arterial tonometry (PAT) signal attenuation,
      desaturation on pulse oximetry, and changes in heart rate. This yielded a PAT
      apnea hypopnea index (AHI). RESULTS: Mean age was 47.0+/-14.8 years, mean body
      mass index 31.0+/-7.6 kg/m(2), mean PSG AHI 23+/-23.9 events per hour, and mean
      PAT AHI 23+/-15.9 events per hour. There was a significant correlation between
      PAT AHI and AHI by PSG (r=0.87, P<0.001). To assess sensitivity and specificity
      of Watch_PAT, we constructed receiver operator characteristic curves using a
      variety of AHI threshold values (10, 15, 20, and 30 events per hour). Optimal
      combinations of sensitivity and specificity for the various thresholds were
      82.6/71.4, 93.3/73.3, 90.9/84.2, and 83.3/91.7, respectively. CONCLUSIONS: The
      Watch_PAT is a device that can detect OSA with reasonable accuracy. Thus, the
      Watch_PAT may be a useful method to diagnose OSA.

PMID- 14592286
TI  - Development of the obstructive sleep apnea knowledge and attitudes (OSAKA)
      questionnaire.
AB  - STUDY OBJECTIVES: To develop and validate a questionnaire that assesses
      physicians' knowledge and attitudes about obstructive sleep apnea (OSA): the
      Obstructive Sleep Apnea Knowledge and Attitudes (OSAKA) questionnaire. DESIGN:
      Questionnaire study. SETTING: Physicians associated with the Washington
      University Physicians Network. PARTICIPANTS: Twenty physicians in the pilot
      testing and 115 physicians in the final testing of the instrument. INTERVENTIONS:
      Physicians completed the OSAKA questionnaire containing sections regarding
      knowledge about OSA (18 items), attitudes about OSA (five items), and
      demographics of the study participants. MEASUREMENTS AND RESULTS: Knowledge
      scores ranged from 0 to 18 (mean+/-SD=13.3+/-2.8). Individual knowledge items did
      not differ significantly by gender or by whether or not respondents had completed
      subspecialty training. The five attitude items were significantly correlated with
      one another. Knowledge scores correlated with the 5-item attitude scale. There
      was a negative correlation between age and knowledge (r=-0.368, P<0.001) and
      between age and the single attitude item pertaining to physicians' confidence in
      managing patients with OSA (r=-0.198, P=0.036); thus, the older the respondent,
      the lower the knowledge score and the less confident they were in managing
      patients with OSA. CONCLUSIONS: The OSAKA appears to be a useful instrument to
      measure physicians' knowledge about OSA, their views on its importance as a
      clinical disorder, and their confidence in identifying and managing patients with
      this disorder.

PMID- 14592287
TI  - Changes in brain morphology associated with obstructive sleep apnea.
AB  - OBJECTIVE: Obstructive sleep apnea (OSA) causes hypoxemia and fragmented sleep,
      which lead to neurocognitive deficits. We hypothesised that focal loss of
      cortical gray matter generally within areas associated with memory processing and
      learning and specifically within the hippocampus would occur in OSA. METHODS:
      Voxel-based morphometry, an automated processing technique for magnetic resonance
      images, was used to characterise structural changes in gray matter in seven right
      handed, male patients with newly diagnosed OSA and seven non-apneic, male
      controls matched for handedness and age. RESULTS: The analysis revealed a
      significantly lower gray matter concentration within the left hippocampus
      (p=0.004) in the apneic patients. No further significant focal gray matter
      differences were seen in the right hippocampus and in other brain regions. There
      was no difference in total gray matter volume between apneics and controls.
      CONCLUSION: This preliminary report indicates changes in brain morphology in OSA,
      in the hippocampus, a key area for cognitive processing.

PMID- 14592288
TI  - Management of restless legs syndrome by the partial D2-agonist terguride.
AB  - BACKGROUND: Terguride as a partial D2-receptors agonist seems suitable for
      treatment of restless legs syndrome (RLS). METHODS: Nine RLS patients without
      previous dopaminergic therapy received a daily dose of terguride (0.25 mg) 29.9+/
      16.9 (SD) days. RESULTS: Two patients enrolled in the study failed to turn up for
      a successive check up. The seven subjects who were re-examined complied with the
      therapy. Their RLS symptoms improved (as measured on the International RLS
      intensity scale), decreasing from 24.3+/-5.3 to 14+/-4.7 (p=0.014). However, the
      terguride treatment did not significantly alter the daytime sleepiness or the
      subjective duration of nocturnal sleep. The daily dose was doubled in three
      patients who reported insufficient RLS improvement. One of the three patients
      later reported augmentation.

PMID- 14592289
TI  - A case report of an obesity hypoventilation syndrome associated with obstructive
      sleep apnea due to a carotid body paraganglioma.
AB  - BACKGROUND AND PURPOSE: To the best of our knowledge, the association between an
      obstructive sleep apnea syndrome (OSAS) due to a neck mass and an obesity
      hypoventilation syndrome (OHS) has not been reported. PATIENTS AND METHODS: We
      report the case of a patient with obesity hypoventilation syndrome (OHS) in whom
      OSAS caused by a carotid body paraganglioma contributed to recurrent bouts of
      severe alveolar hypoventilation. RESULTS AND CONCLUSIONS: The complete surgical
      excision of the paraganglioma resulted in the cure of the OSAS and contributed to
      a clear improvement of the clinical symptoms of OHS.

PMID- 14592292
TI  - Sleep-disordered breathing.

PMID- 14592293
TI  - Is nasal continuous positive airway pressure treatment cost effective? Using a
      standard economic evaluation checklist as a basis for assessment of a cost
      effectiveness evaluation of nasal continuous positive airway pressure (nCPAP)
      treatment.

PMID- 14592294
TI  - Should we aggressively evaluate and treat sleepiness in the elderly?

PMID- 14592295
TI  - Sleep episodes in Parkinson's disease: more questions remain.

PMID- 14592296
TI  - Depression in the sleep center: are we treating the whole patient?

PMID- 14592297
TI  - Sleep problems, stimulants, and ADHD: true, true, unrelated?

PMID- 14592298
TI  - Identification and evaluation of obstructive sleep apnea prior to
      adenotonsillectomy in children: is there a problem?

PMID- 14592299
TI  - Assessment of sleepiness and unintended sleep in Parkinson's disease patients
      taking dopamine agonists.
AB  - OBJECTIVE: We sought to determine if patients with Parkinson's disease (PD),
      taking dopamine agonists (DAs) and reporting unintended sleep episodes (SEs),
      exhibit physiologically defined daytime sleepiness and can thus be differentiated
      from those taking DAs but not reporting SEs. METHODS: Twenty-four patients with
      abnormal Epworth Sleepiness Scale scores of >10 who were taking DAs were enrolled
      into one of two groups: those with SEs (SE+, n=16) and those without (SE-, n=8).
      Three consecutive days of testing included two nights of polysomnography followed
      by the Multiple Sleep Latency Test (MSLT). RESULTS: Overall frequency of
      pathological sleepiness (MSLT <5 min) was 42% (10/24). Mean levels of sleepiness,
      frequencies of pathological sleepiness, and naps with stage 2 or REM-sleep were
      similar between SE+ and SE- groups. Sleep tendency was similar in patients
      prescribed pergolide, ropinirole, and pramipexole combined with levodopa.
      Polysomnography testing revealed no significant differences between the groups in
      total sleep time, sleep efficiency, sleep architecture, or presence of restless
      legs syndrome or periodic leg movements. There was no relation between degree of
      nocturnal sleep disturbance and level of daytime sleepiness. CONCLUSIONS: The
      results of this study suggest SEs in PD patients occur upon a background of
      excessive daytime sleepiness and are unrelated to nocturnal sleep or use of a
      specific DA.

PMID- 14592300
TI  - Melatonin for treatment of REM sleep behavior disorder in neurologic disorders:
      results in 14 patients.
AB  - OBJECTIVE: To describe the treatment response with melatonin for rapid eye
      movement (REM) sleep behavior disorder (RBD) associated with other neurologic
      disorders. BACKGROUND: Clonazepam has been considered the treatment of choice for
      RBD. However, an alternative treatment is desirable for those with RBD refractory
      to clonazepam, for those who experience intolerable side-effects with clonazepam,
      and for those in whom clonazepam precipitates or aggravates obstructive sleep
      apnea (OSA). To date, there is minimal published data and limited follow-up
      regarding the use of melatonin for patients with RBD associated with other
      neurologic syndromes and disorders. DESIGN/METHODS: The response to melatonin
      treatment for RBD was reviewed on consecutive patients the investigators treated
      with this agent at Mayo Clinic Rochester from January 2000 to June 2001. The
      coexisting neurologic disorders, reasons for using melatonin, effective doses,
      side-effects, and duration of follow-up were also reviewed on all patients.
      RESULTS: Fourteen patients were commenced on melatonin over the specified time
      period (13 male, median RBD onset age 56 years, range 20-77 years). The
      coexisting neurologic findings/disorders were dementia with Lewy bodies (n=7),
      mild cognitive impairment with mild parkinsonism (n=2), multiple system atrophy
      (n=2), narcolepsy (n=2), and Parkinson's disease (n=1). The reasons for using
      melatonin in these cases were incomplete response of RBD to clonazepam in six
      patients, existing cognitive impairment in five, intolerable side-effects with
      clonazepam in two, and presence of severe obstructive sleep apnea and narcolepsy
      in one. With seven patients continuing to use clonazepam at 0.5-1.0 mg/night, RBD
      was controlled in six patients, significantly improved in four, and initially
      improved but subsequently returned in two; no improvement occurred in one patient
      and increased RBD frequency/severity occurred in one patient. The effective
      melatonin doses were 3 mg in two cases, 6 mg in seven cases, 9 mg in one case,
      and 12 mg in two cases. Five patients reported side-effects, which included
      morning headaches (2), morning sleepiness (2), and delusions/hallucinations (1);
      these symptoms resolved with decreased dosage. The mean duration of follow-up was
      14 months (range 9-25 months), with eight patients experiencing continued benefit
      with melatonin beyond 12 months of therapy. CONCLUSIONS: In this series,
      persistent benefit with melatonin beyond 1 year of therapy occurred in most but
      not all patients. Melatonin can be considered as a possible sole or add-on
      therapy in select patients with RBD. Prospective, long-term, controlled trials
      with melatonin are warranted in a larger number of patients with RBD associated
      with a variety of neurologic symptoms and disorders.

PMID- 14592301
TI  - Accuracy of sleep perceptions among insomnia sufferers and normal sleepers.
AB  - OBJECTIVE: To examine the distribution, consistency, and correlates of sleep time
      perceptions in primary insomnia sufferers and normal sleepers across settings
      (laboratory and home). METHODS: Fifty-two middle-aged and older insomnia
      sufferers and 49 matched normal sleepers underwent multiple nights of laboratory
      and home polysomnography (PSG) and provided concurrent subjective estimates of
      their sleep. Descriptive statistics, cluster analyses, and inferential tests were
      used to examine the nature of sleep time perceptions, identify subgroups with
      distinctive patterns such as perceptions, and explore factors that may contribute
      to these subgroups' distinctive sleep perceptions. RESULTS: Consistent with
      previous studies, the insomnia sufferers, as a group, showed a greater tendency
      to underestimate the time they slept than did the normal sleepers, but the
      accuracy of sleep time perceptions varied widely within each sample.
      Correlational analyses showed that study participants in each sample showed a
      moderate level of consistency in how accurately they estimated sleep time across
      nights. Subsequent cluster analyses conducted to identify subgroups with
      distinctive patterns of sleep time perceptions yielded four subgroups within the
      insomnia sample and three subgroups within the normal sleeper sample. Although
      the sleep setting significantly affected sleep perceptions for one insomnia
      subgroup, both laboratory and home objective-subjective sleep comparisons
      provided similar impressions regarding the relative accuracy of each subgroup's
      nocturnal sleep/wake perceptions. Finally, varying patterns of subgroup
      differences were noted across several common psychometric measures. CONCLUSIONS:
      The underestimation of sleep time is not a generic characteristic that separates
      all insomnia sufferers from normal sleepers. Sleep setting, personality traits,
      and perhaps constitutional factors appear to influence perceptions of sleep and
      wake time duration.

PMID- 14592302
TI  - Identification and evaluation of obstructive sleep apnea prior to
      adenotonsillectomy in children: a survey of practice patterns.
AB  - OBJECTIVES: Some data suggest that the clinical diagnosis of obstructive sleep
      apnea (OSA) in a child should be confirmed by polysomnography before
      adenotonsillectomy (AT), but otolaryngology literature generally does not agree
      and few studies have examined surgical practice patterns. METHODS: We mailed, to
      603 members of two North American otolaryngology societies, surveys about
      children aged 5.0-12.9 years upon whom they performed ATs in the previous year.
      RESULTS: A total of 183 otolaryngologists estimated that they had performed
      24,000 ATs. Reported major surgical indications, not mutually exclusive, included
      recurrent throat infections (for 42% of procedures), obstructed breathing of any
      type (59%), OSA (39%), poor school performance (17%), and poor attention (11%).
      Pre-operative evaluations included an office-based, sleep-related history in 93%
      of children, any objective testing for OSA in <10%, and laboratory-based
      polysomnography in <5%. Surgeons with academic affiliations, higher volumes of
      ATs, and pediatric specialization reported lower percentages of ATs performed for
      recurrent tonsillitis as opposed to other indications. CONCLUSIONS: As a common
      indication for AT, OSA now rivals recurrent throat infection. No more than 12% of
      school-aged children who undergo AT for OSA have polysomnography prior to the
      procedure. Indications for AT may depend, in part, on practice settings and
      otolaryngologists' backgrounds.

PMID- 14592303
TI  - The effect of stimulants on sleep characteristics in children with attention
      deficit/hyperactivity disorder.
AB  - OBJECTIVE: To investigate the effects of stimulant medications on subjective and
      objective sleep characteristics of children with attention deficit/hyperactivity
      disorder (ADHD) compared with control children. METHODS: An observational study
      in the sleep clinic and the community. Children with characteristics of ADHD,
      both stimulant-medicated (n=53), and non-medicated (n=34), together with control
      children (n=53) completed a sleep habits questionnaire prior to undergoing full
      overnight polysomnographic assessment. RESULTS: Medicated and non-medicated ADHD
      subjects were reported to have more sleep disturbances compared with controls.
      Both groups of ADHD children also demonstrated decreased REM sleep percentage
      compared with controls (P=0.006 for ADHDmed; P=0.02 for ADHDnon). However, the
      use of stimulant medication (n=53) was not associated with differences in
      subjective sleep quality or objective sleep measures, compared to ADHD children
      not taking any medication (n=34; P=n.s.). CONCLUSIONS: Despite the high
      prevalence of reported sleep disturbance in children with ADHD, stimulant
      medication appears to have minimal effects on subjective and objective sleep
      characteristics in children with reported ADHD.

PMID- 14592304
TI  - Sleep and breathing in professional football players.
AB  - OBJECTIVES: To evaluate sleep in professional football players and describe
      clinical features of players at risk for sleep for sleep-disordered breathing
      (SDB). METHODS: The Multivariable Apnea Prediction (MAP) index was used to
      stratify players into high (MAP> or =0.5) and low (MAP<0.5) risk for SDB. Players
      from both risk groups were randomly selected for overnight polysomnography, with
      over-sampling from the High-risk group. Of 302 players from eight professional
      football teams; 52 underwent attended polysomnography. Anthropometrics including
      neck circumference, airway size (Mallampati score, maxillary overjet) and
      sleepiness measured by Epworth scores (ESS) were recorded. The primary outcome
      measures were ESS and an apnea-hypopnea index (AHI) > or =10. RESULTS: Ninety-two
      percent of players were <30 years old (mean (SD) age: 25.5+/-2.7 years) with
      large necks (45.2+/-3.6 cm) and elevated BMI (31.5+/-4.6). More than 20% of
      players had an ESS>10 with ESS highest in habitual snorers. An AHI of > or =10
      was found in 13 (34%, 95% confidence interval (CI) 21-50%) high-risk players but
      only one (7%, 95% CI 1-31%) of 14 low-risk players. Offensive (9) or defensive
      (3) linemen accounted for the majority of the positive cases. Based on our
      sample, we estimate the prevalence of SDB to be 14% (2-25%). CONCLUSIONS:
      Excessive daytime sleepiness (EDS) is present in a large fraction of professional
      football players. Some but not all of this may be due to an increased prevalence
      of SDB. Further study is required to understand all of the factors responsible
      for EDS and to determine which of the biggest players will have SDB, which may
      impact not only performance and productivity but also future health.

PMID- 14592305
TI  - Contextual factors and perceived self-reported sleepiness: a preliminary report.
AB  - OBJECTIVES: The purpose of the present study was to determine whether contextual
      factors affect self-reported sleepiness. Specifically, when a reference situation
      is held constant (e.g. watching television), does the respondent's position,
      location, or interest in the activity alter sleepiness rating. We also evaluated
      interactions between an individual's level of sleepiness and the effect of these
      contextual factors. METHOD: This is a prospective survey conducted at a teaching
      hospital. Samples were drawn from four populations: a general non-patient
      population (n=53), a geriatric population (n=22), a medical resident population
      (n=18), and patients referred for sleep evaluation (n=53). We developed and
      administered a questionnaire that included a list of activities varied according
      to respondent's position, location, or interest in the activity. This
      questionnaire, along with the Epworth Sleepiness Scale (ESS), was administered to
      146 individuals. RESULTS: Overall, we found significant differences (P<0.01) in
      self-reported sleepiness when contextual factors were varied. However, the
      influence of contextual factors declined as a function of increasing sleepiness
      (estimated using ESS scores). CONCLUSIONS: The results of this preliminary study
      indicate that contextual factors can influence self-reported sleepiness rating;
      however, this influence diminishes as sleepiness increases. Thus, clarifying
      context may improve test sensitivity in more alert individuals but does not
      appear to add incremental value to self-reported sleepiness in sleepy patients.

PMID- 14592306
TI  - A prospective 8 week trial of nasal interfaces vs. a novel oral interface
      (Oracle) for treatment of obstructive sleep apnea hypopnea syndrome.
AB  - OBJECTIVE: To compare efficacy, compliance rates, and side effects of a new
      strapless oral interface, the Oracle, with available nasal masks over 8 weeks of
      use for the treatment of obstructive sleep apnea hypopnea syndrome (OSAHS).
      METHODS: A total of 38 patients with OSAHS (respiratory disturbance index (RDI)
      >/=15/h) were enrolled after the diagnostic polysomnogram for subsequent
      continuous positive airway pressure (CPAP) therapy. After randomization,
      therapeutic pressures during a titration study were determined for 21 patients in
      the oral group and 17 patients in the nasal group. Comparisons for nasal and oral
      interfaces were made for baseline patient characteristics, average hours of CPAP
      use, side effects from therapy, and among questionnaires evaluating patients'
      subjective responses to therapy at months 1 and 2. RESULTS: No significant
      difference was observed in the average hours of CPAP use between the oral (4.5+/
      2.1; 5.5+/-2.6) and nasal groups (4.0+/-2.6; 4.8+/-2.5) for either month 1 or 2
      (P>0.05). The dropout rates were similar for both groups after 8 weeks of
      therapy. However, patients in the nasal group had higher occurrences of side
      effects such as nasal congestion, dryness, and air leaks, whereas patients in the
      oral group experienced more oral dryness and gum pain. CONCLUSION: Oral delivery
      of CPAP with the Oracle is an effective and suitable alternative for patients
      with OSAHS.

PMID- 14592307
TI  - Excessive daytime sleepiness in Parkinson's disease as assessed by Epworth
      Sleepiness Scale (ESS).
AB  - OBJECTIVE: To assess daytime sleepiness in patients with Parkinson's disease (PD)
      using the Epworth Sleepiness Scale (ESS). MATERIAL AND METHODS: One hundred and
      forty-nine patients with PD (126 men, 23 women) and 115 age matched controls
      recruited from relatives of medical staff or spouses and other family members
      accompanying patients to the Movement Disorder Clinic of the All India Institute
      of Medical Sciences in New Delhi were included in the study. An ESS score of > or
      =8 was considered abnormal. Data obtained were analyzed using Chi square test for
      categorical variables and Student's t-test for continuous variables. RESULTS: The
      mean age of patients with PD was 58.37 (S.D.=10.45) years, and that of controls
      56.50 (S.D.=11.45) years, with a mean duration of disease of 5.68 (S.D.=3.85)
      years. The mean ESS score was 4.9 (S.D.=3.63) and 2.17 (S.D.=2.54) in PD patients
      and controls, respectively (P<0.05). Thirty-two patients with PD (21%) had an ESS
      score of >8 whereas only 3% of controls scored > or =8 on the ESS (P<0.05).
      Higher ESS scores were associated with a higher Hoehn and Yahr (H&Y) stage of
      disease and higher Unified Parkinson's Disease Rating Scale (UPDRS) (part I, III
      and total) scores (P<0.019, P<0.013 and P<0.011, respectively). CONCLUSION:
      Excessive daytime sleepiness was more common in PD patients as compared to
      controls. Higher ESS scores correlated significantly with higher H&Y stage and
      higher UPDRS (part I, III and total) scores.

PMID- 14592308
TI  - Sleep disorders and depressive feelings: a global survey with the Beck depression
      scale.
AB  - OBJECTIVES: Patients with (chronic) sleep disorders are prone to depression.
      Until now studies on the prevalence of depression in the various sleep disorders
      focused mainly on obstructive sleep apnea patients and narcolepsy. Studies in
      other common sleep disorders are scarce. The aim of our study was to estimate the
      prevalence of depressive feelings in the various sleep disorders diagnosed in a
      Center for Sleep and Wake Disorders. METHODS: We included 917 consecutive
      patients (age between 14 and 84 years, median age: 49, 396 male and 521 female),
      seen in our center for sleep and wake disorders during 2001 and first half of
      2002. The diagnosis was based on the history taken at the outpatient-clinic and
      two consecutive 24-h polysomnographic recordings at home (APSG). The final
      decisions on the diagnosis were made according to the ASDA international
      classification of sleep disorders. The severity of depressive feelings was based
      on the Beck depression scale. RESULTS: Overall, the prevalence of depressive
      feelings was high. There were no significant differences in age and gender. In
      psychophysiological insomnia, inadequate sleep- and wake hygiene, sleep state
      misperception and periodic limb movement disorder/restless legs syndrome some
      form of depression occurred in more than half of the patients. Moderate to severe
      depression was found in 3.5% of the patients. CONCLUSION: The study suggests that
      the use of a depression scale in the daily routine of diagnosing and treating
      sleep disorders should be encouraged in order to optimise diagnosis and therapy
      in these patients.

PMID- 14592310
TI  - Sleep disordered breathing may not be an independent risk factor for diabetes,
      but diabetes may contribute to the occurrence of periodic breathing in sleep.
AB  - OBJECTIVE(S): (a) To determine if self-reported diabetes mellitus is
      independently associated with sleep-disordered breathing (SDB); (b) to determine
      if diabetes mellitus is specifically associated with central sleep apnea
      including periodic breathing (Cheyne-Stokes breathing pattern) during sleep.
      STUDY POPULATION: The study population reflected participants in the on-going
      Sleep Heart Health Study (SHHS). Analyses were conducted utilizing data obtained
      from 4872 SHHS participants without prevalent cardiovascular disease (CVD) and
      1002 participants with self-reported CVD, defined as hospitalization for non
      fatal coronary heart disease, congestive heart failure, myocardial infarction,
      coronary artery bypass graft, and stroke. METHODS: SHHS methodologies have been
      previously reported and include performance of overnight, in-home polysomnography
      (PSG), which recorded variables reflecting sleep architecture and breathing,
      permitting identification of obstructive and central apneas, hypopneas, periodic
      breathing and oxyhemoglobin saturation (SpO(2)). Anthropomorphic metrics as well
      as systemic blood pressure measurements were obtained at the time of PSG. Other
      health data were available from questionnaires and the data sets of the parent
      cohorts from whom SHHS participants were recruited. The investigators assessed
      and compared breathing parameters, sleep architecture and CVD variables in
      diabetic and non-diabetic participants. The relationships between diabetes and
      the various study parameters, independent of potential confounders, were examined
      by multivariable modeling. Linear regression modeling was employed to examine the
      relationship between continuously distributed variables such as respiratory
      disturbance index log (RDI). The relationships between diabetes and dichotomous
      outcome variables such as central apnea index (CAI), obstructive apnea index
      (OAI), periodic breathing and the percentage of time spent at various levels
      below SpO(2) 90% were examined by the logistic regression model. Age, gender,
      race, BMI and neck circumference were forced into all multivariable analyses
      since these factors are associated with both diabetes mellitus and SDB. RESULTS:
      The investigators reported that the prevalence of CVD risk factors including
      increased BMI, waist circumference, neck circumference, triglycerides, reduced
      HDL cholesterol and hypertension was greater in diabetic than non-diabetic
      participants. Native Americans represented a disproportionately high percentage
      of the diabetic population. Unadjusted data obtained from participants without
      prevalent CVD indicated that the mean RDI was higher in the diabetic
      participants. Moreover, there was a greater percentage of diabetic participants
      in the higher RDI categories (e.g. 23.8% of the 470 diabetics and 15.6% of the
      4402 non-diabetics had RDI>15, P<0.001). Similarly, the unadjusted data indicated
      that a significantly greater proportion of the diabetic participants spent >5%
      and >10% of sleep time below SpO(2) 90%, compared with the non-diabetic
      participants. The unadjusted data from participants without prevalent CVD
      indicated that the diabetic and non-diabetic participants did not differ with
      regard to distribution by category of OAI severity (e.g. > or =2 events/h, > or
      =3 events/h, or > or =4 events/h). On the other hand, although the prevalence of
      central apneas was low, a significantly greater proportion of diabetic
      participants were in the CAI categories (> or =2 events/h and > or =3 events/h)
      than non-diabetic subjects. There was no difference between diabetic and non
      diabetic individuals with regard to CAI prevalence in the > or =4 events/h
      category. Of note, a greater percentage of diabetic patients exhibited periodic
      breathing (3.8% vs. 1.8%, diabetic and non-diabetic participants, respectively,
      P=0.002). Repeating the above analyses with inclusion of the participants with
      prevalent CVD did not change these relationships, and in fact, the differences
      between diabetic and non-diabetic participants with respect to central events and
      periodic breathing became more evident (the data forre evident (the data for this
      were not provided in the paper). Linear regression analyses demonstrated that
      BMI, age and male gender were independently related to increased RDI among
      participants without prevalent CVD. Furthermore, after adjusting for age, gender,
      race, BMI and neck circumference, there was no difference in geometric mean RDI
      between the diabetic and non-diabetic participants. The adjusted odds of having
      RDI> or =15 and the adjusted odds for spending> or =5% or > or =10% of sleep time
      with SpO(2) <90% did not differ between the diabetic and non-diabetic
      individuals. The investigators also examined sleep architecture in the study
      cohort. There were no differences between the diabetic and non-diabetic groups
      with regard to the adjusted proportion of time spent in non-REM sleep stages,
      although the mean percent time spent in REM sleep was 1.1% less in the diabetic
      individuals. The findings were the same with or without inclusion of participants
      with known CVD. Even after adjustment for potential confounders, in a sample
      without or with prevalent CVD, diabetic participants had increased adjusted odds
      for periodic breathing odds ratio (1.8, 95% confidence interval (CI) with a range
      of 1.02--3.15 in diabetic participants without prevalent CVD vs. 1.74, 95% CI
      with a range of 1.16--2.62 in diabetic participants with prevalent CVD). There
      was a suggestion of increased odds for CAI in diabetic subjects when analyzing
      populations with and without prevalent CVD. CONCLUSION: The authors concluded
      that diabetes mellitus is associated with sleep apnea but that this association
      is largely explained by risk factors in common for both disorders, most notably
      obesity. After adjusting for confounding factors there was no difference between
      diabetic and non-diabetic participants with regard to obstructive events.
      However, even after adjusting for potential confounders, there was a greater
      prevalence of periodic breathing in diabetic subjects. Although not reaching
      statistical significance, there was a suggestion of an increased prevalence of
      central events in the diabetic population, particularly when the sample included
      participants with known CVD. The investigators believed it unlikely that the
      findings were attributable to underlying congestive heart failure in as much as
      the diabetic subjects without prevalent CVD exhibited increased prevalence of
      periodic breathing and possibly increased central events. The authors proposed
      that diabetes mellitus might be a cause of SDB, mediated through autonomic
      neuropathy that may alter ventilatory control mechanisms. In this context, the
      authors commented that autonomic neuropathy may cause perturbations in
      ventilatory control by altering chemoreceptor gain or altering cardiovascular
      function (although the authors discounted underlying congestive heart failure as
      an explanation for the higher prevalence of periodic breathing in diabetic
      participants). To reinforce their conclusions, the authors cited the literature
      indicating increased prevalence of sleep apnea in diabetic patients with
      autonomic dysfunction, as well as the association between Shy--Drager syndrome,
      in which autonomic insufficiency is a constitutive element, and central sleep
      apnea.

PMID- 14592311
TI  - Non-opioid analgesics and the risk of restless leg syndrome-a spurious
      association?
AB  - OBJECTIVES: The aim of this study was to evaluate the prevalence and risk factors
      of restless leg syndrome in a secondary care patient population maintained on
      tricyclic and serotonin re-uptake inhibiting antidepressants. STUDY DESIGN:
      Prospective observational study. STUDY POPULATION: Two hundred and forty-three
      patients of a single practice specializing in the treatment of affective and
      anxiety disorders. Patients younger than 30 years and those with neurologic
      diseases such as Parkinson's disease, multiples sclerosis and dementia were
      excluded, as well as those with schizophrenia or other illusional disturbances,
      eating disorders, histories of opioid or codeine-containing analgesic abuse or of
      alcohol or illicit drug abuse. Patients remained in the study population only if
      they had gained complete or partial recovery of their anxiety and/or depressive
      symptoms and been treated for at least 6 months in the practice's ambulatory care
      (85.0% of the patients were finally included). METHODS: Histories of leg
      discomfort, akathisia, medication use and socio-demographic factors were assessed
      at the time of enrolment. RLS was assumed if all minimal criteria of the
      international RLS study group were fulfilled. RLS patients also had a neurologic
      examination focusing on signs and symptoms of neuropathy. It is unclear whether
      those without RLS were also examined neurologically. RLS case status was assessed
      at 6-month intervals for patients in the study. It is unclear if the reported RLS
      prevalence reflects case status at enrolment and/or during the treatment course.
      The prevalence of various pain syndromes, as well as the intake of analgesics and
      average coffee intake per day was compared between those with and without RLS.
      Lifetime and current treatment exposure to antidepressants and dopamine
      antagonists was evaluated according to RLS status. It is unclear what the mean
      treatment time was. Various univariant, descriptive statistics were used. The
      statistical analysis and logistic regression was applied using RLS case status as
      the dependent and co-morbidities, and medications/treatments as independent
      variables. RESULTS: The prevalence of RLS among the patients included in the
      analysis was 27.0%, with female patients more often affected than men (31.0% vs.
      19.0%). RLS symptom severity during the course of treatment was low for 43 of 65
      cases. Somatic co-morbidities were more prevalent in RLS affected women and less
      prevalent in RLS affected men than in gender specific non-RLS patients. No
      significant differences were observed for lifetime exposure to dopamine
      antagonist between those with and without RLS (38.0% vs. 35.0%). Chronic pain
      syndromes were observed more often in RLS cases (women: 86.0% vs. 32.0%, men:
      62.5% vs. 29.0%). Twelve percent of those without RLS and 75.0% of RLS cases had
      a history of regular intake of analgesics prior to study enrolment. In a
      multivariate logistic regression model the authors found RLS case status to be
      associated with the intake of analgesics (OR: 25.5, P<0.001), psychiatric co
      morbidity (OR: 2.97, P=0.01) and an interaction between age and the intake of
      analgesics (OR: 2.6, P=0.03). CONCLUSIONS: A 27.0% prevalence of RLS was found in
      this highly selected population treated with tricyclic and serotonin re-uptake
      inhibiting antidepressants. The authors infer from their results that regular
      intake of analgesics is a risk factor for RLS and that the observed association
      of gender with RLS might be explained by a higher intake of analgesics in women
      compared to men. They further conclude that the intake of analgesics, rather than
      the pain co-morbidity itself, enhances the risk of RLS.

PMID- 14592312
TI  - Does a modest loss of sleep affect neurocognitive functioning of children?

PMID- 14592314
TI  - Spindle frequency remains slow in sleep apnea patients throughout the night.
AB  - BACKGROUND: Our previous data suggested that in normal sleep the frequency of
      individual sleep spindles would be related to sleep depth and possibly to sleep
      pressure. Thus far spindle frequency patterns in patients with sleep disorders
      have not been studied. It would be expected that the spindle frequencies might be
      affected by sleep fragmentation disturbing the sleep process. METHODS: Twelve
      apnea patients with age- and sex-matched control subjects were studied with whole
      night sleep recordings. Sleep spindles were visually selected and their frequency
      was determined by spectral analysis. RESULTS: Sleep spindles of the patients were
      in general slower than in the control subjects. As in our previous study, the
      frequency of the spindles in the middle-part of the non-rapid eye movement (NREM)
      sleep episodes increased towards the end of the night in the control group,
      whereas in the patient group no such increase was found. CONCLUSIONS: The slow
      spindle frequencies in apnea patients could indicate disturbed sleep and altered
      neural mechanisms in the structures regulating sleep spindle activity.

PMID- 14592316
TI  - The timing of sleep opportunities in a seven-night sleep restriction.

PMID- 14592318
TI  - Epworth sleepiness scale?

PMID- 14592317
TI  - The origin of speech ease: evolution of the human upper airway and its functional
      implications for obstructive sleep apnea. Editorial commentary: the great leap
      forward: the anatomic basis for the acquisition of speech and obstructive sleep
      apnea by Terence M. Davidson.

PMID- 14592319
TI  - Preliminary observations on the effects of sleep time in a sleep restriction
      paradigm.
AB  - OBJECTIVE: To evaluate of the effect of 7 days of sleep restriction--with sleep
      placed at the beginning of night or early morning hours - on sleep variables,
      maintenance of wakefulness test, and serum leptin. METHODS: After screening young
      adults with questionnaires and actigraphy for 1 week, eight young adult males
      were recruited to participate in a sleep restriction study. The subjects were
      studied for baseline data for 2.5 days, with 8.5 h per night in bed, and then
      over 7 days of sleep restriction to 4 h per night with a 22:30 h bedtime for half
      the group and a 02:15 h bedtime for the other half. At the end of study, after
      one night of ad libitum sleep, subjects again had 2 days of 8.5 h in bed.
      Wakefulness was continuously verified and tests, including Maintenance of
      Wakefulness (MWT), were performed during the scheduled wake time. Blood was drawn
      six times throughout the 24 h of the 7th day of sleep restriction and after 2
      days of the post-restriction schedule. RESULTS: There was individual variability
      in response to sleep restriction, but independent of group distribution, MWT was
      significantly affected by sleep restriction, with the early morning sleep group
      having less decrease in MWT score. Sleep efficiency was also better in this
      group, which also had shorter sleep latency. Independent of group distribution
      there was a greater increase in the percentage of slow wave sleep than rapid eye
      movement sleep, despite a clear internal variability and variability between
      subjects. Peak serum leptin was significantly decreased with 7 days of sleep
      restriction for all subjects. CONCLUSION: Sleep restriction to 4 h affected all
      subjects, but there were individual and group differences in MWT and sleep data.
      In this group of young adult males (mean age 19 years), there was a better
      overall adaptation to the early morning sleep, perhaps related to the general
      tendency in most adolescents to present some phase-delay during late teen-aged
      years.

PMID- 14592320
TI  - The Great Leap Forward: the anatomic basis for the acquisition of speech and
      obstructive sleep apnea.
AB  - Obstructive sleep apnea is an anatomic illness caused by evolutionary changes in
      the human upper respiratory tract. These changes include shortening of the
      maxillary, ethmoid, palatal and mandibular bones, acute oral cavity-skull base
      angulation, pharyngeal collapse with anterior migration of the foramen magnum,
      posterior migration of the tongue into the pharynx, descent of the larynx and
      shortening of the soft palate with loss of the epiglottic-soft palate lock-up.
      While it is commonly believed that some of these changes had positive selection
      pressures for bipedalism, binocular vision and locomotion, development of voice,
      speech and language ultimately became a substantial contributing factor. Here it
      is shown that these changes are the anatomic basis of obstructive sleep apnea.

PMID- 14592321
TI  - Measurement properties of the Epworth sleepiness scale.

PMID- 14592322
TI  - The impact of somatic health problems on insomnia in middle age.
AB  - OBJECTIVE: The objective of this study is to assess the impact on insomnia
      symptoms of somatic diseases, psychological factors, living habits and life
      events during the previous year. BACKGROUND: Although health problems are a
      significant cause of insomnia, psychosocial factors are considered to be even
      more important. The relative impact of these and other factors on insomnia calls
      for further evaluation. METHODS: A questionnaire study in a randomly selected
      middle-aged population in Finland (N=626, 264 men and 362 women). RESULTS: In our
      study, 9.8% of men and 17.0% of women reported the occurrence of insomnia at
      least once a week during the previous 3 months. Insomniacs perceived their health
      as 'poor' or 'rather poor' more often than others and depression, allergic
      rhinitis, asthma, hypertension and heart symptoms such as arrhythmias were more
      common among them. Insomnia was not a side-effect of the treatment of these
      diseases; lack of medical treatment was associated with a higher incidence of
      insomnia. Work-related factors such as 'moving to a poorer job or to poorer
      working conditions' during the past year increased the possibility of insomnia,
      while moving house seemed to have a positive effect. When comparing these
      associations in logistic regression models, nervousness and tension were,
      however, the factors most significantly associated with insomnia. CONCLUSIONS:
      Psychosocial factors appeared to be more significantly associated with prolonged
      insomnia than somatic health problems.

PMID- 14592323
TI  - An automatic ambulatory device for detection of AASM defined arousals from sleep:
      the WP100.
AB  - OBJECTIVES AND BACKGROUND: Arousals from sleep are associated with increased
      sympathetic activation and therefore with peripheral vasoconstriction. Sleep
      fragmentation in the form of multiple arousals is associated with daytime
      somnolence and cognitive impairment; however, manual scoring of arousal is time
      consuming and problematic due to relatively high inter-scorer variability. We
      have recently shown that automated analysis of in-lab recorded peripheral
      arterial tone (PAT) signal and the pulse rate derived from it can accurately
      assess arousals from sleep as defined by the American Academy of Sleep Medicine
      (AASM). In the current study we sought to extend these findings to the
      Watch_PAT100 (WP100), an ambulatory device measuring PAT, oximetry and
      actigraphy. METHODS: Sixty-eight subjects (61 patients referred to the sleep lab
      with suspected obstructive sleep apnea and seven healthy volunteers, mean age
      46.3+/-14.2 years) underwent a whole night polysomnography (PSG) with
      simultaneous recording of PAT signal by the ambulatory WP100 device. The PSG
      recordings were blindly manually analyzed for arousals based on AASM criteria,
      while PAT was scored automatically based on the algorithm developed previously.
      RESULTS: There was a significant correlation between AASM arousals derived from
      the PSG and PAT autonomic arousals derived from the WP100 (R=0.87, P<0.001), with
      a good agreement across a wide range of values. The sensitivity and specificity
      of PAT in detecting patients with at least 20 arousals per hour of sleep were
      0.80 and 0.79, respectively, with a receiver operating characteristic curve
      having an area under the curve of 0.87. CONCLUSIONS: We conclude that automatic
      analysis of peripheral arterial tonometry signal derived from the ambulatory
      device Watch_PAT100 can accurately identify arousals from sleep in a simple and
      time saving fashion.

PMID- 14592324
TI  - Comparison of the NovaSom QSG, a new sleep apnea home-diagnostic system, and
      polysomnography.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is a serious, common, and
      underdiagnosed disorder that challenges health care resources. While
      polysomnography (PSG) represents the standard diagnostic test for OSA, portable
      devices provide an alternative diagnostic tool when issues of cost, time,
      geographic availability, or other constraints pose impediments to in-lab testing.
      This study compares the NovaSom QSG, a new sleep apnea home diagnostic system, to
      PSG both in the laboratory and in the home. METHODS: Fifty-one consecutive adults
      referred to the sleep lab for suspicion of OSA underwent one night of in-lab,
      simultaneous recording of PSG and NovaSom QSG in addition to using the NovaSom
      QSG at home for three nights. Two separate comparisons were made using the apnea
      hypopnea index (AHI): in-lab PSG to in-lab NovaSom QSG and in-lab PSG to home
      NovaSom QSG. RESULTS: Using a clinical cut-off of AHI=15, the sensitivity and
      specificity of the in-lab NovaSom QSG vs. PSG were 95% and 91%, respectively. For
      home NovaSom QSG vs. in-lab PSG, the sensitivity was 91% and specificity was 83%.
      The intra-class correlation coefficient for the agreement between three separate
      nights of NovaSom QSG home data was 0.88. CONCLUSIONS: In a patient population
      suspected of having OSA, the NovaSom QSG demonstrated acceptable sensitivity and
      specificity both in the lab and self-administered in the home, when compared to
      PSG.

PMID- 14592325
TI  - Prevalence of patent foramen ovale in subjects with obstructive sleep apnea: a
      transcranial Doppler ultrasound study.
AB  - BACKGROUND: Under particular conditions a patent foramen ovale (PFO) can
      potentially give rise to ischemic stroke by means of paradoxic embolization. In
      obstructive sleep apnea syndrome (OSAS) right to left shunting (RLSh) can occur
      through PFO during periods of nocturnal apnea. Our study aimed to evaluate the
      prevalence of PFO diagnosed by means of transcranial Doppler (TcD) in subjects
      with OSAS. METHODS: Seventy-eight consecutive subjects with OSAS (mean age 53+/
      12 years) and 89 normal controls (mean age 48+/-9 years) underwent TcD with
      intravenous application of agitated physiological saline solution. The test was
      performed on patients at rest and during Valsalva maneuver. RESULTS: PFO was
      present in 21 out of 78 patients with OSA (27%) and in 13 out of 89 control
      patients (15%). Seventeen out of 21 patients with OSA showed PFO only during
      Valsalva maneuver (85%) with respect to 12 out of 13 subjects of the control
      group (92%). Prevalence of PFO in OSAS was statistically different with respect
      to the control group (P<0.05). However, no statistically significant differences
      could be found for the prevalence of provocative-only shunting PFO with respect
      to already at rest shunting PFO in patients with OSAS with respect to the control
      group. CONCLUSIONS: Prevalence of PFO in subjects with OSA is significantly
      higher than in normal controls. The shunt is frequently present only during
      Valsalva maneuver.

PMID- 14592326
TI  - Antioxidant capacity in obstructive sleep apnea patients.
AB  - OBJECTIVES: Obstructive sleep apnea syndrome (OSA) results in oxygen desaturation
      and arousal from sleep. Free oxygen radicals are highly reactive molecules, which
      can be produced by the OSA phenomenon known as hypoxia/reoxygenation. Hypoxic
      conditions, such as OSA, may also result in transient depletion of cellular
      reductants, which constitute a main line of antioxidant defense. Both apneas and
      hypopneas usually end in arousal, where reoxygenation causes the production of
      reactive oxygen species (free radicals). Living organisms have developed complex
      antioxidant systems to counteract reactive oxygen species and to reduce their
      damage. We evaluated the antioxidant capacity in serum from OSA patients and
      healthy people in order to confirm the hypothesis that there is a relationship
      between oxidative stress and OSA. MATERIALS AND METHODS: A physician interviewed
      25 participants, determining age, smoking habits and symptoms such as excessive
      daytime sleepiness and snoring. Physical examination and polysomnography were
      performed during patients' hospitalization. Antioxidant capacity was measured in
      blood samples by Trolox Equivalent Antioxidant Capacity assay. RESULTS: Seventeen
      out of 25 subjects had an apnea/hypopnea index (AHI) greater than 10 (OSA group).
      The measurement of antioxidant capacity did not differ between the OSA patients
      and our healthy sample (of 25 subjects, seven with an AHI less than 10).
      Furthermore, patients with severe OSA (AHI >20, N=14) had linearly negative
      correlation between antioxidant capacity in their blood samples and AHI (R=
      0.551, P=0.041). CONCLUSIONS: Reduced antioxidant capacity in serum is an index
      of excessive oxidative stress. Patients with severe OSA have reduced values of
      antioxidant capacity.

PMID- 14592327
TI  - Spindle frequency remains slow in sleep apnea patients throughout the night.
AB  - BACKGROUND: Our previous data suggested that in normal sleep the frequency of
      individual sleep spindles would be related to sleep depth and possibly to sleep
      pressure. Thus far spindle frequency patterns in patients with sleep disorders
      have not been studied. It would be expected that the spindle frequencies might be
      affected by sleep fragmentation disturbing the sleep process. METHODS: Twelve
      apnea patients with age- and sex-matched control subjects were studied with whole
      night sleep recordings. Sleep spindles were visually selected and their frequency
      was determined by spectral analysis. RESULTS: Sleep spindles of the patients were
      in general slower than in the control subjects. As in our previous study, the
      frequency of the spindles in the middle-part of the non-rapid eye movement (NREM)
      sleep episodes increased towards the end of the night in the control group,
      whereas in the patient group no such increase was found. CONCLUSIONS: The slow
      spindle frequencies in apnea patients could indicate disturbed sleep and altered
      neural mechanisms in the structures regulating sleep spindle activity.

PMID- 14592328
TI  - Non-dreamers.
AB  - OBJECTIVE: Assess incidence and clarify whether diagnostic correlates exist for
      sleep laboratory patients reporting a lack of dream recall. To awaken, during
      polysomnographically defined sleep including rapid eye movement (REM) sleep,
      individuals reporting never having experienced a dream, and determine whether
      they report dreaming. METHODS: Study # 1 - Incidence and polysomnographic
      correlates of sleep lab patients responding on questionnaire that they had never
      experienced dreaming. Study # 2 - Phone interviews with those individuals
      reporting non-dreaming on questionnaire to reassess incidence. Study # 3 - After
      reassessment, individuals (non-dreamers - # 16) are awakened during
      polysomnographic defined sleep (including REM sleep) and queried about dream
      recall. This group is compared statistically to a group (rare-dreamers - # 12)
      that reported dreaming as an extremely rare occurrence (mean dream recall latency
      - 13.5 years). RESULTS: Study # 1: Incidence of questionnaire reported non
      dreaming in this sleep laboratory population is 6.5% (N=534) and is associated
      with the diagnosis of obstructive sleep apnea (specificity 95.6% for respiratory
      disturbance index >15). Study # 2 - Individuals who report after interview to
      have never experienced dreaming are more unusual (0.38% of this sleep laboratory
      population). Study # 3 - None of the non-dreamers (# 16) reported dream recall
      after waking in the sleep laboratory (36 awakenings in total for this group).
      This group does not differ, based on polysomnographic, clinical, or demographic
      variables, from the rare-dreaming group that occasionally reported dreams when
      awakened (3/12 patients, 3/32 awakenings) - a finding consistent with the reports
      of previous studies. CONCLUSION: The experience of dreaming may not be as
      ubiquitous as generally accepted. The group of non-dreamers evaluated in this
      study reports never having recalled a dream and reports no dreams when awakened
      during polysomnographicly defined sleep. These individuals might not experience
      dreaming.

PMID- 14592329
TI  - Treatment of nocturnal eating syndrome and sleep-related eating disorder with
      topiramate.
AB  - BACKGROUND: Sleep-related eating disorder (SRED) and nocturnal eating syndrome
      (NES) combine features of sleep disorders and eating disorders. Treatment of
      these nocturnal eating behaviors has been directed towards underlying
      identifiable sleep or eating disorders using dopaminergic or opioid agonists, as
      well as anorectic agents, at times with the addition of sedatives. METHODS: Two
      patients with SRED and two with NES, who had failed multiple previous trials of
      pharmacotherapy and psychotherapy, were treated in a naturalistic, open-label
      fashion with topiramate at night. Reduction in nocturnal eating was graded based
      on self-report. Weight was computed at the outset of, and during, topiramate
      treatment. RESULTS: One patient with NES had a complete elimination of nocturnal
      eating with topiramate, two patients (one with NES, one with SRED) had a marked
      response, and one patient (with SRED) had a moderate response. Mean dose was 218
      mg, though three patients noted an improvement at 100 mg. Notable weight loss was
      observed in all patients (mean of 11.1 kg). Benefits of topiramate treatment have
      been maintained for a mean period of 8.5 months. CONCLUSIONS: Topiramate may be
      of benefit for patients with NES or SRED in reducing nocturnal eating, improving
      nocturnal sleep, and producing weight loss.

PMID- 14592330
TI  - Sleep disorder in alien hand syndrome.
AB  - A 63-year-old right-handed woman developed an alien hand syndrome (AHS) after an
      acute infarction in the territory of the left anterior cerebral artery. The
      uncontrolled hand movements were present during the daytime and eventually
      disturbed sleep. Polysomnography revealed that these motor actions only appeared
      when the patient was awake. These awakenings emerged mostly from NREM sleep stage
      2 during the first half of the night. There was no evidence of any epileptiform
      activity, dyssomnia or parasomnia. These movements were controlled making her
      wear an oven mitt during sleep. The temporal distribution of this motor activity
      seems to follow the progressive hyperpolarization of anterior horn neurons that
      occurs when sleep deepens. The accommodation of the grasp reflex in AHS probably
      helps control this unwanted motor activity.

PMID- 14592331
TI  - Normal hypocretin-1 (orexin-A) cerebrospinal fluid level in a previously reported
      case of severe, life-long insomnia with motor hyperactivity.

PMID- 14592338
TI  - Editor's corner: restless legs syndrome, a common disease uncommonly diagnosed.

PMID- 14592339
TI  - Restless legs syndrome (RLS): the continuing development of diagnostic standards
      and severity measures.

PMID- 14592332
TI  - Flow into sleep.

PMID- 14592340
TI  - Validation: a dangerous and difficult claim to make.

PMID- 14592341
TI  - Restless legs syndrome: diagnostic criteria, special considerations, and
      epidemiology. A report from the restless legs syndrome diagnosis and epidemiology
      workshop at the National Institutes of Health.
AB  - BACKGROUND: Restless legs syndrome is a common yet frequently undiagnosed
      sensorimotor disorder. In 1995, the International Restless Legs Syndrome Study
      Group developed standardized criteria for the diagnosis of restless legs
      syndrome. Since that time, additional scientific scrutiny and clinical experience
      have led to a better understanding of the condition. Modification of the criteria
      is now necessary to better reflect that increased body of knowledge, as well as
      to clarify slight confusion with the wording of the original criteria. SETTING:
      The restless legs syndrome diagnostic criteria and epidemiology workshop at the
      National Institutes of Health. PARTICIPANTS: Members of the International
      Restless Legs Syndrome Study Group and authorities on epidemiology and the design
      of questionnaires and scales. OBJECTIVE: To modify the current criteria for the
      diagnosis of restless legs syndrome, to develop new criteria for the diagnosis of
      restless legs syndrome in the cognitively impaired elderly and in children, to
      create standardized criteria for the identification of augmentation, and to
      establish consistent questions for use in epidemiology studies. RESULTS: The
      essential diagnostic criteria for restless legs syndrome were developed and
      approved by workshop participants and the executive committee of the
      International Restless Legs Syndrome Study Group. Criteria were also developed
      and approved for the additional aforementioned groups.

PMID- 14592342
TI  - Validation of the International Restless Legs Syndrome Study Group rating scale
      for restless legs syndrome.
AB  - BACKGROUND: There is a need for an easily administered instrument which can be
      applied to all patients with restless legs syndrome (RLS) to measure disease
      severity for clinical assessment, research, or therapeutic trials. The
      pathophysiology of RLS is not clear and no objective measure so far devised can
      apply to all patients or accurately reflect severity. Moreover, RLS is primarily
      a subjective disorder. Therefore, a subjective scale is at present the optimal
      instrument to meet this need. METHODS: Twenty centers from six countries
      participated in an initial reliability and validation study of a rating scale for
      the severity of RLS designed by the International RLS study group (IRLSSG). A ten
      question scale was developed on the basis of repeated expert evaluation of
      potential items. This scale, the IRLSSG rating scale (IRLS), was administered to
      196 RLS patients, most on some medication, and 209 control subjects. RESULTS: The
      IRLS was found to have high levels of internal consistency, inter-examiner
      reliability, test-retest reliability over a 2-4 week period, and convergent
      validity. It also demonstrated criterion validity when tested against the current
      criterion of a clinical global impression and readily discriminated patient from
      control groups. The scale was dominated by a single severity factor that
      explained at least 59% of the pooled item variance. CONCLUSIONS: This scale meets
      performance criteria for a brief, patient completed instrument that can be used
      to assess RLS severity for purposes of clinical assessment, research, or
      therapeutic trials. It supports a finding that RLS is a relatively uniform
      disorder in which the severity of the basic symptoms is strongly related to their
      impact on the patient's life. In future studies, the IRLS should be tested
      against objective measures of RLS severity and its sensitivity should be studied
      as RLS severity is systematically manipulated by therapeutic interventions.

PMID- 14592343
TI  - Factor analysis of the International Restless Legs Syndrome Study Group's scale
      for restless legs severity.
AB  - OBJECTIVE: The International Restless Legs Syndrome Study Group has developed and
      validated a ten-item scale for assessing the severity of the restless legs
      syndrome. This International Restless Legs Severity Scale (IRLS) is reported to
      have a high degree of internal consistency and it has generally been used as a
      single scale. This study uses a factor analytic approach to evaluate the IRLS for
      possibly useful subscales. METHODS: A large convenience sample (n=516) of self
      identified restless leg syndrome patients completed the IRLS over the Internet.
      Data were analyzed using principal component analyses. RESULTS: Two primary
      factors were identified, one with six items related to symptom severity and a
      second with three items related to impact of the symptoms on life. These
      accounted for 41.8 and 22.5% of the variance, respectively. CONCLUSIONS: The IRLS
      can be evaluated using separate subscale scores: one for symptoms and the other
      symptom impact. The relative merits of these subscale scores versus the score for
      the entire test need to be evaluated in different situations in further studies,
      in especially the ones involving assessing responsiveness to treatment effects.

PMID- 14592344
TI  - The Johns Hopkins telephone diagnostic interview for the restless legs syndrome:
      preliminary investigation for validation in a multi-center patient and control
      population.
AB  - STUDY OBJECTIVES: To develop and validate a telephone diagnostic interview (the
      Johns Hopkins telephone diagnostic interview for restless legs, abbreviated TDI)
      for diagnosis of the restless legs syndrome (RLS). DESIGN AND METHODS: Using the
      International RLS Study Group diagnostic criteria, specific questions were
      developed reflecting the diagnostic features of RLS. Seventy-five subjects (37
      previously diagnosed RLS patients and 38 controls self-reported to be free of
      RLS) were interviewed by three expert interviewers blinded to each others'
      interviews and the patient's clinical status. The interviewers diagnosed each
      subject based on responses to the TDI. RESULTS: The interviewers overall
      correctly diagnosed 72 of 75 individuals. Minimum interviewer sensitivity and
      specificity were 97 and 92%, respectively. The intraclass correlation coefficient
      (ICC) was used to quantify inter-rater reliability for the three interviewers.
      The ICC for diagnosis was 0.95. The ICC calculated on other key items in the
      interview exceeded 0.80 in all cases. The patients were predominantly older
      individuals with long-standing RLS; 19 of them scored at the highest level of
      severity on the Johns Hopkins Restless Legs Severity Scale (JHRLSS). The
      interviewers had more difficulty with assessing the controls accurately, some of
      whom were probably incorrectly self-categorized as not having RLS. CONCLUSIONS:
      The TDI is a sensitive, specific, and reliable instrument for diagnosing RLS by
      experienced interviewers in a brief, anonymous telephone encounter.

PMID- 14592345
TI  - Restless legs syndrome in hemodialysis patients in India: a case controlled
      study.
AB  - OBJECTIVE: To assess the prevalence of restless legs syndrome (RLS) in Indian
      patients on hemodialysis as compared to controls. METHODS: One hundred and twenty
      one consecutive hemodialysis patients and 99 controls were evaluated using a
      standard predesigned questionnaire. The control group comprised completely normal
      healthy adults who were being evaluated as renal donors. Nerve conduction studies
      were done in those patients diagnosed with RLS. RESULTS: RLS was present in eight
      hemodialysis patients (6.6%) and none of the controls. Patients (87.5%) with RLS
      had delayed sleep onset. Nerve conduction showed evidence of sensori-motor
      neuropathy in five patients and a normal study in one patient. When we compared
      the patients with RLS to those without RLS, there was no significant difference
      in their age, duration of hemodialysis, hemoglobin, blood urea, creatinine, serum
      ferritin or use of erythropoeitin. CONCLUSIONS: The prevalence of RLS was 6.6% in
      patients on hemodialysis; and 0% in controls, which is much lower than that
      reported from the West.

PMID- 14592346
TI  - Different sleep characteristics in restless legs syndrome and periodic limb
      movement disorder.
AB  - OBJECTIVE: Periodic limb movements in sleep (PLMS) may or may not be associated
      with restless legs syndrome (RLS). The number of PLMS is commonly used to assess
      the clinical severity and sleep quality of patients with RLS. It is still unclear
      whether the sleep disorder of periodic limb movement disorder (PLMD) is different
      from the sleep disorder in RLS. METHODS: We compared the polysomnograms (PSGs) of
      27 prospectively recruited RLS patients and 26 retrospectively recruited age- and
      sex-matched PLMD patients without RLS symptoms. RESULTS: The PLM index and the
      index of arousal-associated PLMS (PLMAI) were significantly higher in PLMD,
      whereas the index of EEG arousals not associated with any sleep-related event was
      significantly higher in RLS. In PLMD patients, the PLMI correlated negatively
      with the percentage of PLMS associated with an arousal, whereas this correlation
      was positive in RLS patients. Further, RLS patients spent significantly more time
      in wake-after-sleep onset, had more rapid eye movement sleep (REM) and less sleep
      stage I. CONCLUSIONS: We conclude that the sleep disorder in RLS differs from
      that in PLMD. Spontaneous, not PLM associated EEG arousals should be included in
      the assessment of the sleep structure of patients with RLS, particularly in
      studies concerned with drug-efficacy.

PMID- 14592347
TI  - Development of restless legs syndrome after dopaminergic treatment in a patient
      with periodic leg movements in sleep.
AB  - Periodic leg movements in sleep (PLMS) unrelated to restless legs syndrome (RLS)
      are a polysomnographic finding with a controversial clinical value. We describe a
      patient with isolated periodic leg movements in sleep (without any awake or sleep
      complaints), who developed severe diurnal RLS symptoms a few months after
      starting dopaminergic treatment, a phenomenon mimicking augmentation. The diurnal
      RLS symptoms disappeared after withdrawal of the dopaminergic drugs. Serum
      ferritin levels were relatively low (31-61 mcg/l; normal: 30-400 mcg/l). Since
      low levels of ferritin have been implicated in the genesis of RLS, and
      augmentation is a phenomenon associated with RLS, our findings here suggest that
      asymptomatic PLMS may have pathogenic mechanisms similar to RLS. Isolated PLMS
      and RLS could be, at least in some cases, different clinical forms of the same
      disorder. The conjunction of dopaminergic treatment with low ferritin levels may
      expose a patient with isolated PLMS to the development of RLS. Discontinuation of
      dopaminergic drugs in patients with isolated PLMS who develop RLS during the
      course of the treatment would be a reasonable recommendation.

PMID- 14592352
TI  - The narcoleptic borderland.

PMID- 14592353
TI  - Chronic insufficient sleep and its recovery.

PMID- 14592354
TI  - The narcoleptic borderland: a multimodal diagnostic approach including
      cerebrospinal fluid levels of hypocretin-1 (orexin A).
AB  - OBJECTIVES: Biological markers of narcolepsy with cataplexy (classical
      narcolepsy) include sleep-onset REM periods (SOREM) on multiple sleep latency
      tests (MSLT), HLA-DQB1*0602 positivity, low levels of cerebrospinal fluid (CSF)
      hypocretin-1 (orexin A), increased body mass index (BMI), and high levels of CSF
      leptin. The clinical borderland of narcolepsy and the diagnostic value of
      different markers of narcolepsy remain controversial and were assessed in a
      consecutive series of 27 patients with hypersomnia of (mainly) neurological
      origin. METHODS: Diagnoses included classical narcolepsy (n=3), symptomatic
      narcolepsy (n=1), narcolepsy without cataplexy (n=4), idiopathic hypersomnia
      (n=5), hypersomnia associated with psychiatric disorders (n=5), and hypersomnia
      secondary to neurological disorders or of undetermined origin (n=9). Clinical
      assessment included BMI, Epworth Sleepiness Scale (ESS), Ullanlinna Narcolepsy
      Scale (UNS), and history of REM-symptoms (sleep paralysis, hallucinations). HLA
      typing, electrophysiological studies (conventional polysomnography, MSLT, 1-week
      actigraphy), and measurements of CSF levels of hypocretin and leptin were also
      performed. RESULTS: Hypocretin-1 was undetectable in three patients with classic
      narcolepsy and detectable in the remaining 24 patients. Other narcoleptic markers
      also frequently found in patients without narcolepsy included ESS>14 (78% of 27
      patients), UNS>14 (75%), REM symptoms (30%), sleep latencies on MSLT<5 min (41%),
      >/=2 SOREM (30%), DQB1*0602 positivity (52%), BMI>25 (52%), and increased CSF
      leptin (48%). Hypersomnia was documented by an increased time 'asleep' in 41% of
      patients. Overlapping clinical and electrophysiological findings were seen mostly
      in patients with narcolepsy without cataplexy, idiopathic hypersomnia, and
      psychiatric hypersomnia. CONCLUSIONS: (1) Hypocretin dysfunction is not the
      'final common pathway' in the pathophysiology of most hypersomnolent syndromes
      that fall on the borderline for a diagnosis of narcolepsy. (2) The observed
      overlap among these hypersomnolent syndromes implies that current diagnostic
      categories are not entirely unambiguous. (3) A common hypothalamic, hypocretin
      independent dysfunction may be present in some of these syndromes.

PMID- 14592355
TI  - Sleep architecture in normal Caucasian and Hispanic children aged 6-11 years
      recorded during unattended home polysomnography: experience from the Tucson
      Children's Assessment of Sleep Apnea Study (TuCASA).
AB  - OBJECTIVE: To obtain normative sleep architecture data from unattended home
      polysomnography in Caucasian and Hispanic children aged 6-11 years. DESIGN AND
      SUBJECTS: Unattended home polysomnography was performed on a single night in
      Caucasian and Hispanic children aged 6-11 years as part of the Tucson Children's
      Assessment of Sleep Apnea Study (TuCASA), a cohort study designed to examine the
      prevalence and correlates of sleep disordered breathing. A subset of 42 children
      enrolled in TuCASA who had no symptoms of any sleep disorder and had
      polysomnograms without technical recording problems. RESULTS: Sleep architecture
      in preadolescent Caucasian and Hispanic children was not different between boys
      and girls. However, total sleep time (TST), sleep efficiency (SLE) and time spent
      in REM sleep declined with increasing age. In addition, the number of sleep to
      wake stage shifts was slightly higher in younger children. Hispanic children had
      less Stage 3/4 sleep (18+/-1 vs. 22+/-1%, P</=0.02) and correspondingly more
      Stage 2 sleep (55+/-2 vs. 50.0+/-1%, P</=0.02) than their Caucasian counterparts.
      CONCLUSIONS: Using unattended home polysomnography, indices of sleep duration and
      architecture are not different between preadolescent boys and girls. However,
      with increasing age, TST and SLE decreased. In addition, there are differences in
      sleep architecture between Caucasians and Hispanics, which may be an important
      consideration in the evaluation of children with sleep disorders.

PMID- 14592356
TI  - School performance, race, and other correlates of sleep-disordered breathing in
      children.
AB  - OBJECTIVES: Childhood sleep-disordered breathing (SDB) has been associated with
      poor school performance. Both problems are common among African-American (AA)
      children, but potential confounders such as low socioeconomic status (SES) and
      obesity have not been well studied. METHODS: Children in second and fifth grades
      at six urban elementary schools were evaluated by teachers' ratings and year-end
      reading and math assessments. Risk for SDB was assessed with the validated
      parental Pediatric Sleep Questionnaire, and SES by qualification for school lunch
      assistance. RESULTS: Among 146 children whose parents completed surveys, risk for
      SDB was associated with AA race, low SES, and poor teacher ratings (P<0.01), but
      not assessment scores (P>0.1). In multiple regression models, poor school
      performance was consistently and independently predicted by low SES (P<0.01) but
      not by AA race or SDB risk. Risk for SDB was associated with low SES before, but
      not after body mass index (BMI) was taken into account. CONCLUSIONS: The SDB
      symptoms, AA race, and low SES all vary to some extent with poor school
      performance, but the only consistent and independent covariate of performance is
      SES. Risk for SDB is associated with low SES, perhaps because of a third
      variable, namely high BMI.

PMID- 14592357
TI  - Effect of the new Medicare guideline on patient qualification for positive airway
      pressure therapy.
AB  - BACKGROUND: New Medicare criteria for prescribing continuous positive airway
      pressure (CPAP) recognize hypopnea as a sleep disordered breathing event. In so
      doing, hypopnea was redefined as requiring a 4% oxygen desaturation. The criteria
      omit electroencephalogram (EEG) arousals from the definition. This study was
      designed to assess how the new Medicare guideline changes CPAP eligibility.
      METHODS: Polysomnograms from 113 consecutive patients with obstructive sleep
      apnea were scored using both a definition for hypopnea that considered EEG
      arousals and the new Medicare definition that does not consider EEG arousal. CPAP
      eligibility was evaluated and compared. RESULTS: Sixteen percent of all patients
      and 41% of patients apnea+hypopnea index </=20 did not qualify for CPAP under the
      new Medicare guidelines. CONCLUSIONS: The new Medicare guidelines may
      underestimate OSA event occurrence and thereby deny CPAP therapy to many
      patients.

PMID- 14592358
TI  - Can periodic limb movement disorder be diagnosed without polysomnography? A case
      control study.
AB  - OBJECTIVES: (1) To determine whether clinical information can predict the
      presence of periodic limb movement disorder (PLMD). (2) To examine whether
      clinical data correlate with PLMD severity. METHODS: Sixty-one adult patients (48
      males and 13 females, aged 55.1+/-14.1 years) with PLMD (without a clinical
      diagnosis of restless legs syndrome) were compared with 61 control patients
      without PLMD (43 males and 18 females, aged 49.6+/-16.1 years) in this case
      control study. All patients completed a detailed questionnaire which included (1)
      demographics, (2) sleep complaints, (3) medical disorders, (4) use of medication,
      nicotine, and caffeine, and (5) history of nocturnal motor/sensory leg symptoms.
      All patients underwent standard polysomnography. RESULTS: The PLMD and control
      groups were similar in the prevalence of insomnia, hypersomnia, diabetes,
      peripheral neurologic disorders, anemia, spinal disease, antidepressant
      medication use, smoking, caffeine intake, and leg pain. Compared with the control
      group, the PLMD group reported more leg kicks (28% vs. 5%, P<0.001) and more
      crawling or aching sensations in legs (28% vs. 11%, P=0.023). The logistic
      regression analysis showed that only age (P=0.044), leg kicks (odds ratio (OR)
      12.70, 95% confidence interval (CI) 2.80-57.63, P=0.001), and crawling or aching
      in legs (OR 5.23, 95% CI 1.16-23.44, P=0.029) were significantly related to the
      presence of PLMD. The positive predictive value of leg kicks in the diagnosis of
      PLMD was 85% and the negative predictive value was 57%. Within the PLMD group,
      only age correlated positively with the PLM-index (r=0.47, P<0.001). Both the PLM
      index and the PLM arousal-index were negatively correlated with sleep efficiency
      on polysomnography (P=0.005 and P=0.006, respectively). CONCLUSIONS: Clinical
      data are not sufficiently predictive of the presence of PLMD to rule in or rule
      out the diagnosis. Polysomnography is required for establishing the diagnosis of
      PLMD in patients with insomnia or hypersomnia.

PMID- 14592359
TI  - Efficacy and safety of modafinil for improving daytime wakefulness in patients
      treated previously with psychostimulants.
AB  - OBJECTIVES: To assess the efficacy and safety of modafinil for improving
      wakefulness in narcolepsy patients treated previously with psychostimulants.
      BACKGROUND: Modafinil has become a standard therapy for improving daytime
      wakefulness in narcolepsy patients and may be a useful therapeutic alternative to
      psychostimulants used to improve waking function in other medical conditions.
      Modafinil is chemically dissimilar to and has a pharmacological profile that
      differs from the psychostimulants. Modafinil has a low abuse potential and is
      well tolerated. METHODS: Patients (N=151) with narcolepsy who had been
      unsatisfactorily treated with dextroamphetamine (N=48), methylphenidate (N=66),
      or pemoline (N=37) were enrolled in this 6-week, open-label, multicenter study.
      Following a 2-week washout period, patients received modafinil once daily (Week
      1, 200 mg; Weeks 2-6, 200 or 400 mg). Efficacy was evaluated at Weeks 1, 2, and 6
      using the Epworth Sleepiness Scale and the Clinical Global Impression of Change.
      Adverse events were monitored throughout the study. RESULTS: Treatment with
      modafinil improved daytime wakefulness versus baseline regardless of which
      psychostimulant was taken previously. Mean ESS scores were improved after 1 week
      of treatment with modafinil. Improvements were maintained throughout the 6 weeks
      of treatment (all P<0.001 versus baseline after washout). At Week 6, 79% of all
      patients were considered to be clinically improved relative to post-washout
      baseline. The most frequent adverse events were headache, nausea, and insomnia;
      the majority of adverse events were mild or moderate in nature. Approximately 70%
      of patients were receiving 400 mg of modafinil once daily at the end of the
      study. CONCLUSION: During this 6-week, open-label study, modafinil was an
      effective and well-tolerated treatment for improving daytime wakefulness in
      narcolepsy patients previously treated with psychostimulants.

PMID- 14592361
TI  - A meta-analysis of sleep changes associated with placebo in hypnotic clinical
      trials.
AB  - OBJECTIVES: The effects associated with placebo (EAP) have been incompletely
      described in clinical trials of insomnia treatment. We conducted a meta-analysis
      of insomnia medication trials for the purpose of estimating the magnitude of
      sleep EAP. METHOD: We reviewed Medline for 1966 through 2000 for the meta
      analysis. The subject heading of insomnia restricted to the subheading of drug
      therapy was crossed against the results of a search on the subjects heading
      placebo and text word placebo. We selected only papers that examined primary
      insomnia, incorporating both placebo and active medication therapies in a
      randomized, double-blind, parallel-group design. We required that results be
      reported for 1, 2, 3, or 4 weeks of treatment, and that outcomes be reported in
      hours/minutes. RESULTS: Five papers satisfied our requirements for eligibility,
      comprising 213 patients receiving placebo for a 2-week interval. Subjective sleep
      latency demonstrated a significant reduction (mean+/-S.E.) of 13.1+/-2.0 min (95%
      confidence interval (CI) 9.2, 17.0) for the placebo group after combining the
      data across studies. Subjective total sleep time demonstrated a significant
      increase of 13.5+/-5.4 min (95% CI 2.9, 24.0). Polysomnographic (PSG) sleep
      latency demonstrated a non-significant reduction of 2.5+/-4.3 min (95% CI -5.9,
      10.9). CONCLUSIONS: The confirmation of EAP in insomnia clinical trials argues
      for the retention of a placebo control in future insomnia clinical trials.

PMID- 14592360
TI  - Effects of antiepileptic drugs on sleep architecture: a pilot study.
AB  - OBJECTIVES: The effects of antiepileptic drugs (AEDs) on sleep architecture are
      not well understood, especially in patients with localization-related epilepsy,
      in whom seizures themselves can disrupt sleep. To clarify the effects of AEDs on
      sleep architecture, we performed a prospective study, looking at sleep
      architecture in patients with epilepsy admitted for video-EEG monitoring.
      METHODS: Adult patients with localization-related epilepsy treated with a single
      AED and admitted between 10/1997 and 04/2001 were included. Control patients on
      no AEDs were also included. Both groups were withdrawn from other AEDs. Overnight
      polysomnography was recorded and was scored according to the standard method.
      Adult patients with localization-related epilepsy on no medication were also
      recorded and served as controls. Patients with no seizure during the recording
      and no seizure in the 24 h preceding the recording were analyzed in this paper.
      Patients with a seizure in the 24 h preceding the recording and patients with a
      seizure during the recording were analyzed separately. RESULTS: A total of 72
      nights were recorded in 39 patients, and patients taking each AED were compared
      to controls. We did not find any statistically significant effect of
      carbamazepine (CBZ). Phenytoin (PHT) disrupted sleep by increasing stage 1 sleep
      (PHT: 13.2+/-7.3%; control: 7.7+/-4.8%; P=0.008), and decreasing slow wave sleep
      (SWS) (PHT: 7.9+/-4.2%; control: 11.3+/-4.4%; P=0.03) and REM sleep (PHT: 13.9+/
      6.2; control: 18.8+/-5.1; P=0.01). Valproic acid (VPA) disrupted sleep by
      increasing stage 1 sleep (VPA: 16.8+/-9.8%; control: 7.7+/-4.8%; P=0.007).
      Gabapentin (GBP) improved sleep by increasing SWS (GBP: 19.4+/-4.2%; control:
      11.3+/-4.4%; P=0.0009). PHT and VPA disrupt sleep in the absence of seizures,
      while CBZ and lamotrigine have no significant effects. GBP improves sleep by
      increasing SWS. CONCLUSIONS: AEDs have differing effects on sleep structure,
      which can be beneficial or detrimental. Consideration of these potential effects
      is important in maintaining optimal sleep in patients with epilepsy.

PMID- 14592363
TI  - Clinical caveat: prior sleep deprivation can affect the MSLT for days.
AB  - It is common practice to forcibly awaken patients from an all-night
      polysomnographic study prior to performance of a multiple sleep latency test
      (MSLT); either for reasons of protocol or for the convenience of the laboratory
      personnel. We report a case of a young woman who, by formal sleep study criteria,
      received the erroneous diagnosis of narcolepsy due to the effects of severe sleep
      deprivation, and document that the effects of prior sleep deprivation require
      more than one night of ad libitum sleep. Forced awakening prior to MSLT may
      permit sleep deprivation or delayed sleep phase syndrome to masquerade as
      narcolepsy or idiopathic central nervous system (CNS) hypersomnia.

PMID- 14592362
TI  - Microsleep and sleepiness: a comparison of multiple sleep latency test and
      scoring of microsleep as a diagnostic test for excessive daytime sleepiness.
AB  - STUDY OBJECTIVE: To compare multiple sleep latency test (MSLT) and scoring of
      microsleep (presence of sleep electroencephalograph between 3 and 15s in an
      epoch) as a diagnostic test for excessive daytime sleepiness (EDS). DESIGN: A
      retrospective study. SETTING: Sleep center at a tertiary care teaching hospital.
      SUBJECTS: Patients referred to a sleep center who had an MSLT and one or more of
      the following symptoms; tiredness, sleepiness, memory loss, accidents/near
      accidents and gap driving. INTERVENTIONS: Full night polysomnography (PSG) and
      next day MSLT were performed. Patients were classified as 'microsleep-positive'
      or 'microsleep-negative' according to presence or absence of microsleep. RESULTS:
      Patients (n=92) were divided into three groups according to their MSLT results;
      group A had an MSLT</=5min (n=38), group B had an MSLT=6-10min (n=26), and group
      C had an MSLT>10min (n=28). The number of patients with symptoms of tiredness and
      memory loss were statistically higher in group A compared with groups B and C
      (P=0.036). The number of patients with symptoms of EDS, in groups B and C, was
      significantly higher in patients with microsleep than without microsleep
      (P<0.05). By a paired McNemar's test, the better performance of adding microsleep
      to MSLT (sensitivity 42.9%; specificity 63.6%) to assess EDS was statistically
      significant (P=0.0096). CONCLUSIONS: Microsleep determination during an MSLT is a
      more sensitive and specific test for EDS as compared to MSLT alone.

PMID- 14592364
TI  - Posttraumatic stress disorder in the spouse of a patient with sleep terrors.
AB  - A 27-year-old woman who developed posttraumatic stress disorder (PTSD) as a
      consequence of her husband's severe sleep terror episode is reported. A 29-year
      old man suddenly aroused from sleep and jumped through the closed second-story
      window of the room he shared with his wife, sustaining major lacerations to his
      arms. He hung onto the roof as his wife screamed at him from the window, and
      eventually climbed back inside. He was evaluated with polysomnography and was
      given the diagnosis of sleep terrors, which was effectively treated with
      behavioral and pharmacologic interventions. During a routine follow-up visit with
      the patient, his wife's PTSD symptoms came to clinical attention and she was
      referred for treatment. She demonstrated marked improvement in her condition
      after an 8 week course of cognitive-behavioral therapy. We conclude that family
      members of patients with sleep disorders manifesting as violent behaviors during
      sleep can suffer psychological trauma even if they are not physically injured.

PMID- 14592365
TI  - Websites on oral appliances for obstructive sleep apnea.

PMID- 14592371
TI  - Roles of orexins in the regulation of feeding and arousal.
AB  - Maintenance of energy homeostasis requires the coordination of systems that
      regulate feeding, autonomic and endocrine functions with those that govern an
      appropriate state of arousal. The hypothalamus play a critical role in
      maintaining energy homeostasis by integrating and coordinating these systems.
      Recent studies have suggested that orexin-containing neurons in the lateral
      hypothalamic area constitute an important central pathway that promotes adaptive
      behavioral and arousal responses to metabolic and environmental signals. This
      article review recent studies on orexin to suggest that orexin neurons play a
      significant role in feeding and arousal regulation, possibly by coordinating the
      complex behavioral and physiological responses of these complementary homeostatic
      functions.

PMID- 14592372
TI  - Sudden infant deaths: arousal as a survival mechanism.
AB  - The mechanisms responsible for sudden infant death syndrome (SIDS) are still
      largely unknown. To explain what factors contribute to the deaths, we suggest a
      model: the '3 S model for SIDS' that includes 'sicknesses', 'stages of
      development' and 'surroundings': (1) 'sicknesses' refers to infectious diseases
      or other medical condition. (2) 'Stages of development' relates to the maturation
      of vital systems including respiratory, neurovegetative or sleep-wake behavioral
      controls. (3) 'Surroundings' refers to environmental conditions that enhance the
      deficiency of cardiorespiratory, vegetative and/or arousal controls. Such
      conditions were identified by epidemiological studies and include the following
      main risk factors: the prone body position during sleep, high environmental
      temperature, maternal smoking or sleep deprivation. An infant could be at higher
      risk for SIDS because of a deficiency in breathing and cardiac autonomic controls
      during sleep, inducing repeated episodes of hypoxia and hypoxemia. The risk is
      increased when the infant has a lower propensity to arouse from sleep and so, to
      autoresuscitate. The accident has a greater probability to occur when an
      infection, or an unfavorable environmental factor aggravates the immature
      cardiorespiratory and sleep/wake behaviors of the infant. The clinical findings
      could be related to the changes reported in the brainstems of SIDS victims.

PMID- 14592373
TI  - Arousal and upper airway resistance (UAR).
AB  - OBJECTIVE: The objective of this study is to investigate upper airway resistance
      (UAR) in infants and children and presence/absence of electroencephalogram (EEG)
      arousal. METHODS: Polysomnography with nasal cannula/pressure transducer and
      esophageal manometry; pattern recognition of sleep disordered breathing (SDB) in
      children. Identification of visually scored arousals in response to SDB. Power
      spectrum analysis of EEG associated with SDB. RESULTS: Several breathing patterns
      and change in heart rate (HR) can be seen with abnormal UAR during sleep. SDB may
      end with or without visual arousal. Power spectrum analysis shows different EEG
      patterns with termination of UAR and SDB. HR is also variably modified.
      CONCLUSIONS: Airway reopening and decline in UAR is associated with variable
      central nervous system activation and only intermittently with arousals.

PMID- 14592374
TI  - Scoring arousals in the home environment.
AB  - Arousals from sleep and consequent sleep disruption may be a causal link between
      sleep-disordered breathing and its sequellae in children. Quantification of
      arousals therefore makes an important contribution to the overall assessment of
      the sleep of a child with suspected obstructive sleep apnea (OSA) or other sleep
      disorders. Arousals are classically defined by changes in the
      electroencephalographic (EEG) channels, but most arousals in children involve
      body movement in addition to EEG changes. Several methods of quantifying arousals
      without the use of EEG have been proposed, with the aim of simplifying testing in
      children with suspected OSA so that it can be safely and efficiently performed in
      the child's home. The following paper gives a background to the assessment of
      arousals from sleep in children, and describes methods for detecting arousals and
      their potential application to recordings performed in a child's home.

PMID- 14592375
TI  - Early steps of awakening process.
AB  - This paper summarizes the main aspects of sleep and waking development and shows
      results about awakening as a function of age. Awakenings come mainly from active
      sleep and their number decreases with age. Understanding the awakening process
      should take into account the development of sleep and waking states and of
      circadian rhythms and homeostatic processes.

PMID- 14592376
TI  - Subcortical arousal response in child patients with obstructive sleep apnea.
AB  - OBJECTIVE: The objective of this study is to assess subcortical arousal response
      (SCA) in child patients with obstructive sleep apnea syndrome (OSAS). METHODS: A
      new index termed SCA was defined as a sigh associated with elevated chin muscle
      activity. According to the duration, SCAs were divided into three types; SCA
      short (1s or more and less than 3s), SCA intermediate (3s or more and less than
      10s), and SCA long (10s or more). We scored SCAs in six child OSAS patients, aged
      2-5 years, before and after adenotonsillectomy. SCAs were also counted in four
      age-matched controls. RESULTS: In the pretreatment records, 45.5% of SCAs were
      associated with electroencephalographic arousals. In all patients, SCA short and
      SCA intermediate decreased after the treatment to the levels in the controls. SCA
      long exhibited no consistent changes after treatment. The incidence of SCAs was
      much higher than arousals previously reported in child OSAS patients as well as
      in normal children. CONCLUSIONS: SCAs, especially SCA short and SCA intermediate,
      are sensitive and useful indices for assessing subcortical involvement in child
      OSAS patients.

PMID- 14592377
TI  - Graded arousal responses in infants: advantages and disadvantages of a low
      threshold for arousal.
AB  - OBJECTIVE: To review studies of upper airway protective reflexes and other
      aspects of arousal from sleep. METHODS: Discussion of pertinent physiological
      studies. CONCLUSIONS: Infant arousal from sleep incorporates two systems. The
      first comprises a group of periodically occurring reflexes serving
      cardiorespiratory homeostatic functions as well as providing for several aspects
      of normal growth and development. The second system is organized to respond to
      acute threats to survival during sleep. Both systems are integrated in a single
      arousal network originating in the brainstem. Full arousal occurs as a
      progression of events occurring sequentially and manifested by various innate
      motor and cardiovascular responses. During an arousal, rostral progression from
      brainstem to cortex is retarded by increasing inhibition which serves to decrease
      cortical arousals thereby preserving the integrity of rapid eye movement and non
      rapid eye movement sleep states. Activation of brainstem arousal reflexes alone
      can cause recovery from obstruction sleep apnea episodes without the need for
      cortical arousal, a phenomenon more characteristic of infants than adults.

PMID- 14592378
TI  - Functional brain imaging using fMRI and optical topography in infancy.
AB  - We performed functional magnetic resonance imaging and optical topography over
      the visual cortex of subjects during sedation with pentobarbital, and 8-Hz
      flickering light was intermittently projected onto their eyelids. Two age groups
      were analyzed: infants <60 days old and those >60 days old (corrected for
      gestational age at birth). The stimulus-related signal change was positive in the
      lateral geniculate nucleus regardless of the infant's age, but it reversed in the
      primary visual cortex from positive in the infants less than 60 days old to
      negative in the infants more than 60 days old (Experiment 1). We also
      investigated spontaneous changes in the cerebral oxygenation state of neonates
      and infants aged 1 month during quiet sleeping by using a form of multi-channel
      near-infrared spectroscopy: non-invasive optical topography. Spatially
      synchronized oscillations of changes in the concentration of oxy-hemoglobin (oxy
      Hb) and deoxy-Hb were observed throughout the occipital cortex in neonates but
      not in the infants aged 1 month. Time series analysis based on the theory of non
      linear oscillations showed that the mean periods of the oscillation for each
      infant ranged from 11 to 18s. The phase lag of oxy-Hb relative to deoxy-Hb was
      stable at about 3 pi/4 in neonates but in the infant aged 1 month, time lag was
      unstable. These findings may be due to rapid synaptogenesis in early life.

PMID- 14592379
TI  - The relationship between mismatch negativity and arousal level. Can mismatch
      negativity be an index for evaluating the arousal level in infants?
AB  - BACKGROUND: Electrophysiological and behavioral studies have shown that stimulus
      relevance contributes to auditory processing in sleep and auditory stimuli
      changes the sleep stages. So we observed changes in auditory processing due to
      sleep stages by recording infant mismatch negativity (MMN) during different
      states and investigated the arousal mechanisms. METHODS: Auditory event-related
      potentials (ERPs) of 26 neonates were recorded using high-density EGI EEG system.
      Stimuli consisted of 1000 Hz tones with 90% probability as standard and 1200 Hz
      with 10% probability as deviant. Study 1 was designed for the confirmation of the
      recording of MMN from neonates and Study 2 for investigating whether an
      appropriate stimulus onset asynchrony (SOA) of the stimulus would induce a clear
      difference in the latency or amplitude. RESULTS: (Study 1) MMN were obtained from
      all subjects. No differences of the latencies, amplitudes and distribution due to
      arousal or sleep stage were observed. After the MMN response occurred, a
      prominent negativity like Nc was seen in response to deviant stimuli in active
      sleep and waking state. (Study 2) No distinct differences between the difference
      states were seen in any SOA. CONCLUSIONS: Only MMN did not characterize the
      arousal or sleep stage. But the modality of the auditory evoked potentials (AEPs)
      may differ according to the state, so further detailed investigation could enable
      the detection of the infants' state using the AEP.

PMID- 14592380
TI  - Physiological relationship between autonomic reactions and arousals in infancy.
AB  - OBJECTIVE: Changes in blood pressure (BP) were measured following auditory
      stimuli in the prone and the supine position to study the correlation between
      arousal from sleep and autonomic responses. METHOD: Two newborns born at term,
      two infants and four children were recorded polygraphically during one night,
      while sleeping in the prone and the supine position. They were exposed to white
      noises of increasing intensities during both rapid eye movement (REM) and non
      rapid eye movement (NREM) sleep in each position. BP changes were measured by
      Finapress in the children and by pulse transient time (PTT) in the infants and
      newborns. RESULTS: Basal systolic BP pressures were lower (P<0.001) and PTT were
      higher (P=0.008) in the prone than in the supine position in children and in
      infants. Following the auditory stimulations, the increases in systolic BP
      (P=0.024) and the decreases in PTT (P=0.006) were smaller in prone than in supine
      position. During cortical arousals, the same findings were found, independently
      of sleep stages. CONCLUSION: Compared with when they are sleeping supine,
      children and infants sleeping prone had lower basal BP and higher PTT and smaller
      changes in BP and PTT after auditory stimulation. Reduced BP changes to stimuli
      could be implicated in the increased arousal thresholds in prone position.

PMID- 14592381
TI  - Structural mechanisms underlying autonomic reactions in pediatric arousal.
AB  - Arousal provides an essential means to restore homeostasis following a system
      perturbation during a quiescent state. The classic definition of 'arousal'
      includes a constellation of cardiovascular, respiratory and somatic muscle
      characteristics, together with activation of the electrocorticogram (ECoG). At
      least two ascending activating systems, a ventral cholinergic and a serotonergic
      ascending system, both interacting with other regional neurotransmitter
      processes, contribute to electrocortical activation, with separate behaviors
      mediated by each system. A number of 'arousal' processes essential for survival
      operate at local levels, and interact with the systems that mediate cortical
      activation. These processes include cerebellar compensatory mechanisms which
      respond to extreme cardiovascular challenges, and limbic structures which respond
      to hypoxia or hypercarbia and the resultant dyspnea. The local processes show
      exceptional cortical arousing properties upon recruitment of some structures,
      such as the amygdala, which has major projections to ascending arousal systems.
      Components of arousal can emerge without ECoG activation and can be mediated at
      local levels which interact with ascending systems.

PMID- 14592382
TI  - Arousal deficiency theory in sudden infant death syndrome with reference to
      neuronal plasticity.
AB  - OBJECTIVE: Among 27,000 infants studied prospectively to characterize their sleep
      wake behavior, 38 infants died under 6 months of age (including 26 infant victims
      of sudden infant death syndrome (SIDS), five with congenital cardiac
      abnormalities, two from infected pulmonary dysplasia, two from septic shock with
      multi-organ failure, one with a prolonged seizure, one from prolonged neonatal
      hypoxemia and one from meningitis and brain infarction). METHOD: The frequency
      and duration of sleep apnea events recorded some 3-12 weeks before the infants'
      deaths were analyzed. Brainstem material from these 38 infants was studied in an
      attempt to elucidate the relationship between sleep apnea and neuronal
      pathological changes in the arousal pathway. The histochemical analyses included
      Bielschowsky staining and the immunohistochemical analyses included the
      evaluation of growth-associated phosphoprotein 43 (GAP43) and of synaptophysin as
      markers for synaptic plasticity. Neurofibrae with positive pathological reactions
      were quantitatively analyzed. Pathological and physiological data were linked for
      each infant. RESULTS: The correlation between sleep apnea and neuronal plasticity
      in the arousal pathway of the SIDS victims was not seen in the control infants
      and the correlation between sleep apnea and neuronal plasticity in the arousal
      pathway found in the control infants was not seen in the SIDS victims.
      CONCLUSION: These findings suggest that neuronal plasticity in the brainstem
      arousal pathway is related with SIDS.

PMID- 14592383
TI  - Arousal responses and risk factors for sudden infant death syndrome.
AB  - BACKGROUND: Failure to arouse from sleep has been postulated as a mechanism to
      explain the final pathway of sudden infant death syndrome (SIDS). METHODS: We
      have reviewed the effects of the major risk factors for SIDS, prone sleep
      position, maternal smoking, prematurity and recent infection on arousability from
      sleep. In human infants it has been consistently demonstrated that arousal from
      sleep in response to a variety of stimuli is more difficult to induce from quiet
      sleep (QS) compared to active sleep (AS) over the first 6 months of life.
      RESULTS: In the prone position both stimulus-induced and spontaneous arousability
      from both QS and AS were impaired at 2-3 weeks and 2-3 months, but not at 5-6
      months of age in both term and preterm infants. In term infants exposed to
      maternal smoking during pregnancy both stimulus-induced and spontaneous
      arousability were impaired when infants slept supine in QS at 2-3 months of age.
      Healthy preterm infants showed no impairment in arousability compared with term
      infants at matched postconceptional ages. However, preterm infants with a history
      of apnoea and bradycardia of prematurity showed decreased arousal responses in
      both QS and AS and this impairment was positively correlated to their 'perinatal
      risk score'. Infants who had recently suffered an infection requiring
      hospitalization showed decreased arousability in QS on the day of discharge when
      compared to 2 weeks later when they were completely well. CONCLUSIONS: In summary
      it has been found that the major risk factors for SIDS identified from
      epidemiological studies also decrease arousability from sleep in infants. We
      propose that this decreased arousability from sleep may be involved in the final
      pathway of SIDS.

PMID- 14592384
TI  - Intraoperative awareness and the depth of anesthesia in children: a perspective
      from pediatric anesthesia.
AB  - The bispectral index (BIS) monitoring, using electroencephalographically-derived
      method, has shown some promise to measure 'depth of anesthesia' for various
      anesthetics. A large fraction of the literature that has investigated BIS
      monitoring demonstrates that BIS correlates well with clinically important
      endpoints and many clinical utility trials have been undertaken in adults to
      prove its effectiveness to improve perioperative patient care. As the use of the
      technology grows, other potential applications have been investigated; BIS as a
      monitor in pediatric anesthesia and BIS as a monitor to measure the depth of
      sleep may serve as examples. If the two are proved useful, these successes may
      bring clinicians another application of this technology: BIS to monitor
      unconsciousness state of babies to prevent sudden infant death syndrome or
      apparent life threatening event.

PMID- 14592386
TI  - Flow-limitation and sleep: exploring the interface of a complex and dynamic
      system.

PMID- 14592385
TI  - A review of functional and structural components of the respiratory center
      involved in the arousal response.
AB  - State-dependent changes influencing both the central chemoreceptor and vagal
      inputs to respiratory neurons may provide useful markers to assess some intrinsic
      factors of the respiratory center. In this paper we discuss the following topics
      from our recent experiences, and their relevance to the assessment of sleep
      related phenomena. (1) 'Post-sigh' apnea appears predominantly during non-REM
      sleep in control subjects, and is a potential marker of respiratory dysfunction
      during this stage of sleep. (2) The disarranged configuration of the arcuate
      nucleus in Fukuyama-type congenital muscular dystrophy may represent a
      disturbance in the tangential migration pathway in the brainstem, and may be
      related to the sudden death that is common in this disorder. The maldevelopment
      of the arcuate nucleus in the victims of sudden infant death syndrome (SIDS) may
      also be related to some abnormality in the differentiation and migration of this
      neuronal population. (3) The onset of hypoglossal nerve activity precedes
      inspiratory activity of the phrenic nerve, possibly representing a latent drive
      from the respiratory rhythm generator. These issues are not only related to
      respiratory rhythmogenesis itself, but are also important in understanding the
      pathological conditions of arousal responses.

PMID- 14592387
TI  - Sleep and cognitive (memory) function: research and clinical perspectives.
AB  - The field of memory and sleep is controversial and extremely interesting, and the
      relationships between thought processes, i.e. cognition and sleep, have recently
      been examined in a variety of clinical and basic research settings, as well as
      being the object of intense interest by the general public. For example, there
      are data which demonstrate that insomnia, as well as specific sleep disorders,
      can have a negative impact on sleep cognition as well as affect daytime patterns
      of cognitive functioning. Thus, sleep, disturbed sleep and the lack of sleep
      appear to affect cognitive and memory functions. An International Workshop
      dealing with Sleep and Cognitive Function: Research and Clinical Perspectives was
      convened in Cancun, Mexico, 1-4 March 1999 under the auspices of the World Health
      Organization Worldwide Project on Sleep and Health and the World Federation of
      Sleep Research Societies. A great number of areas of intersection between sleep
      and cognitive function were examined during the course of the Workshop, such as
      aging, cognition and sleep and the dream process and sleep. The results of these
      discussions are included in a WHO publication (WHO Doc.: MSD/MBD/00.8). In the
      present report we concentrate on presenting a summary of a coherent set of data
      which examine memory consolidation during sleep and the impact of insomnia on
      cognitive functions. Based upon these data, a review of memory and drug effects
      that are sleep-related, and an examination of the relationship between hypnotics
      and cognitive function are included. Finally, a summary of recommendations of the
      Workshop participants is presented.

PMID- 14592388
TI  - Comparison of actigraphic, polysomnographic, and subjective assessment of sleep
      parameters in sleep-disordered patients.
AB  - OBJECTIVE: Comparison of polysomnography (PSG)-derived sleep parameters (total
      sleep time, sleep efficiency, and number of awakenings) to those derived from
      actigraphy and subjective questionnaires. BACKGROUND: Actigraphy is commonly used
      to assist sleep specialists in the diagnosis of various sleep and circadian
      rhythm disorders. However, few validation studies incorporate large sample sizes,
      typical sleep clinic patients, or comparisons with subjective reports of sleep
      parameters. METHODS: Clinical series with 100 consecutive sleep-disordered
      patients (69 men, 31 women, mean age of 49+/-14.7 years) at a tertiary sleep
      disorders center. Sensitivity, specificity, and accuracy measures were obtained
      from epoch-by-epoch comparison of PSG and actigraphic data. Subjective sleep
      parameter data were derived from questionnaires given to subjects in the morning
      following their recording night. RESULTS: We found that total sleep time and
      sleep efficiency did not significantly differ between PSG data and the combined
      data obtained from actigraphy and subjective reports. Using a high-threshold (low
      wake-sensitivity) actigraphic algorithm, the number of awakenings was not
      significantly different from those detected by PSG. CONCLUSIONS: We recommend the
      use of subjective data as an adjunct to actigraphic data in estimating total
      sleep time and sleep efficiency in sleep-disordered patients, especially those
      with disorders of excessive somnolence.

PMID- 14592389
TI  - Variability of respiratory effort in relation to sleep stages in normal controls
      and upper airway resistance syndrome patients.
AB  - OBJECTIVE: Investigation of the role of sleep states on the respiratory effort of
      controls and subjects with upper airway resistance syndrome (UARS) using nasal
      cannula/pressure transducer system and esophageal manometry. PATIENTS AND
      METHODS: One night's monitoring of sleep and breathing, including the
      determination of peak end inspiratory esophageal pressure (respiratory effort)
      with esophageal manometry and flow limitation with nasal cannula. Analysis of the
      data, breath-by-breath, using visual inspection and a computerized program.
      Setting - a university sleep laboratory. Patients were nine men with UARS and
      nine control men matched for age, ethnicity, and body mass index. RESULTS: A
      modulation of respiratory effort by sleep state and stages is seen in all
      subjects, the lowest noted during REM sleep and the highest associated with Slow
      Wave Sleep. When total nocturnal breaths are investigated, a significant
      difference between peak end inspiratory esophageal pressure [(Pes)-considered as
      an index of respiratory effort] is noted between normal subjects and UARS. Two
      specific breathing patterns, seen primarily in UARS patients, are NREM sleep
      stage dependent. Crescendos (defined as more negative peak end inspiratory Pes
      with each successive abnormal breath) occur mostly during stages 1-2 NREM sleep,
      while segments consisting of regular and continuous, breath-after-breath, high
      respiratory efforts are associated with Slow Wave Sleep. Depending on sleep
      stage, visually scored arousal response displays differences in Pes negativity.
      The termination of the abnormal breathing pattern, always well defined with Pes,
      is not necessarily associated with a pattern of 'flow limitation' at the nasal
      cannula tracing, even when a visually scored EEG arousal is present. CONCLUSIONS:
      UARS patients have significantly more breaths, with more negative peak end
      inspiratory Pes, than do control subjects. The modulation of peak end inspiratory
      Pes (an index of respiratory effort) by sleep stage and state differs in UARS
      patients and control subjects. The nasal cannula/pressure transducer system may
      not detect all abnormal breathing pattern during sleep. As indicated by the
      visual sleep scoring, repetitive arousals may lead to more or less severe sleep
      fragmentation.

PMID- 14592390
TI  - Nasal bilevel positive airway pressure therapy in children with a sleep-related
      breathing disorder and attention-deficit hyperactivity disorder: effects on
      electrophysiological measures of brain function.
AB  - OBJECTIVE: To examine the effect of nasal bilevel positive airway pressure
      (BiPAP) treatment for concurrent sleep-related breathing disorders (SRBDs) and
      attention-deficit hyperactivity disorder (ADHD) on electrophysiological measures
      of spontaneous brain activity and auditory stimulus processing. METHODS: Nineteen
      children diagnosed with both SRBD and ADHD participated. Electroencephalogram
      (EEG) activity was recorded during a resting period and an auditory oddball task
      before beginning BiPAP treatment, after 6 months on treatment, and after a
      subsequent 1 week non-treatment period. Treatment effects on EEG and event
      related potentials (ERPs) to target stimuli were examined via topographic
      analysis. RESULTS: Thirteen of the initial 19 children completed 6 months of
      BiPAP therapy, with six lost mainly due to compliance problems. Children on BiPAP
      therapy showed a significant decrease in slow-wave (delta and theta) and an
      increase in fast wave (beta) EEG activity. The P3 component of the ERP showed
      treatment effects in amplitude and latency. CONCLUSIONS: The electrophysiological
      data suggest that SRBDs may contribute to ADHD symptomatology. Treatment of SRBD
      with BiPAP therapy in children with concurrent ADHD can lead to significant
      changes, in the direction of normalization, of the typical electrophysiological
      features of ADHD.

PMID- 14592391
TI  - Sleep complaints and restless legs syndrome in adult type 2 diabetics.
AB  - OBJECTIVE: To determine the prevalence and characteristics of sleep complaints
      and restless legs syndrome (RLS) in type 2 adult diabetics. To test the
      hypothesis that sleep complaints are more common among adult diabetics.
      BACKGROUND: Restless legs syndrome is a common disorder and is a cause of
      insomnia and daytime somnolence. An association between RLS and diabetes mellitus
      has been hypothesized but has not been established. METHODS: Consecutive type 2
      diabetic patients and controls were subjected to sleep questionnaires,
      examinations for sensory neuropathy, and laboratory investigations. RESULTS:
      Diabetics had higher rates of insomnia (50 vs. 31%, P=0.04) and used more
      hypnotics (25.9 vs. 6.0%, P=0.02) than controls. The proportion of diabetics with
      elevated Epworth Sleepiness Scores (> or =12) was higher than controls (15.5
      vs.2.1%, P=0.02). The prevalence of RLS among diabetics was not significantly
      different than in controls (24.1 vs. 12.5%, P=0.1). The prevalence of sensory
      polyneuropathy was similar in diabetics with and without RLS. Age, BMI, duration
      and level of diabetes control, hemoglobin, ferritin and creatinine levels did not
      predict the presence of RLS in diabetics. CONCLUSIONS: Adult type 2 diabetics
      have higher rates of insomnia, excessive somnolence and hypnotic use than
      controls. There is no evidence that RLS is significantly more common in adult
      diabetics.

PMID- 14592392
TI  - Zolpidem reduces the sleep disturbance of jet lag.
AB  - OBJECTIVE: To determine the degree to which zolpidem 10 mg would reduce the sleep
      disruption associated with rapid, eastward transatlantic travel. BACKGROUND:
      Subsequent to rapid transmeridian travel, individuals often complain of jet lag
      which includes transient disturbances in sleep patterns, alertness, appetite and
      mood. Disturbed sleep and impaired alertness appear to be the most debilitating
      symptoms of jet lag. METHODS: This multi-center, double-blind randomized, placebo
      controlled, parallel-groups study involved 138 adult (mean age 44.9 years)
      experienced travelers while on their regular eastward transatlantic assignments
      originating in the US and crossing 5-9 time zones. Subjects were normal sleepers
      when not traveling and had to have traveled overseas at least twice during the
      last 24 months. Subjects were randomized to zolpidem 10 mg or placebo for three
      (optionally four) consecutive nights starting with the first nighttime sleep
      after travel. Sleep was assessed with daily questionnaires. RESULTS: A total of
      130 subjects completed the study. Compared to placebo, zolpidem was associated
      with significantly improved sleep (statistically significant differences at
      nights indicated) longer total sleep time (night 1), reduced number of awakenings
      (nights 1 and 2), and improved sleep quality (nights 1, 2 and 3). Zolpidem was
      not associated with improvement in sleep latency. No unexpected or serious
      adverse events were reported and the most common adverse event was headache in
      both groups (9.2 and 17.6% for placebo and zolpidem, respectively). CONCLUSION:
      In seasoned travelers, zolpidem 10 mg produced significant improvement in sleep
      following rapid transmeridian travel.

PMID- 14592393
TI  - Is (re)titration of nasal continuous positive airway pressure for obstructive
      sleep apnoea necessary?
AB  - OBJECTIVE: To assess changes in nasal continuous positive airway pressure (nCPAP)
      pressure requirements across time in obstructive sleep apnoea (OSA), and whether
      routine retitrations are indicated. BACKGROUND: Most sleep laboratories perform
      one nCPAP titration, although some authors have found changes in pressures with
      time. A cohort of patients with OSA in a randomised controlled trial of nCPAP
      provided us with data on changes in titration pressures with time. METHODS: One
      hundred and one patients with symptomatic OSA (Epworth Sleepiness Scale > or =10,
      and >10 episodes/h of >4% dips in SaO(2) overnight) were recruited to a 1 month
      trial comparing real (autotitrated) and placebo nCPAP. At 1 month all patients
      were titrated and received real nCPAP thereafter. Eighty five were retitrated at
      about 6 months. RESULTS: Average pressures did not change between the initial
      value and 1 month (95th centile, 8.47 (SD 3.00), 8.94 (2.85) cm H(2)O), although
      there were large individual changes (mean difference, +0.47, SD 2.30, range -5 to
      +6 cm H(2)O). There was a small fall at 6 months (mean difference -0.68, SD 2.60,
      range -6 to +6 cm H(2)O, P<0.03) with no suggestion that the changes from 1-6
      months were clinically important. CONCLUSIONS: This study suggests that routine
      nCPAP retitrations are not necessary. In conjunction with other published data,
      the night to night variation we found implies that a nCPAP calibration using an
      algorithm (based on obesity and OSA severity) might be as clinically successful
      as conventional one night titrations. However, further studies will be needed to
      specifically confirm this hypothesis.

PMID- 14592394
TI  - The impact of narcolepsy on psychological health and role behaviours: negative
      effects and comparisons with other illness groups.
AB  - OBJECTIVES: The study sought to (i) assess psychosocial adjustment, disruption
      due to symptoms, and medication problems in narcolepsy, (ii) determine how these
      variables changed with gender, age and medication status, and (iii) compare
      narcolepsy adjustment with three other illness groups. BACKGROUND: Psychosocial
      adjustment to an illness can be conceptualized in terms of people's ability to
      function in their life roles and assessed using the Psychosocial Adjustment to
      Illness Scale-Self Report (PAIS-SR) questionnaire. METHODS: Participants (n=129)
      were recruited via a support group using posted questionnaires. The PAIS-SR was
      supplemented with additional questionnaire material. RESULTS: Males were more
      vulnerable than females in terms of adjustment (notably health care orientation
      and sexual relationships) and younger narcoleptics may have particular vocational
      problems. Unmedicated narcoleptics were least inclined to participate in
      social/leisure activities. Reported disruption due to symptoms was strongly
      associated with both psychological distress and overall psychosocial adjustment
      and was most notable in those taking both stimulants and tricyclic
      antidepressants. Narcoleptics reported more adjustment problems in comparison to
      three other illness groups (cardiac, mixed cancer and diabetes). A table of
      normative PAIS-SR values for narcolepsy was developed. CONCLUSIONS: Poor
      adjustment in terms of health care orientation and psychological distress are of
      particular concern. Health care that can reduce the disruption due to symptoms is
      especially important for adjustment.

PMID- 14592395
TI  - Sleep structure following status epilepticus.
AB  - OBJECTIVES: To determine the effect of status epilepticus (SE) on sleep.
      BACKGROUND: SE has a high incidence of morbidity and mortality. The study of
      sleep structure following SE may have implications for recovery in these
      patients. METHODS: Twenty-four hour polysomnography was recorded in a 52-year-old
      patient following generalized convulsive SE not complicated by other medical or
      neurologic conditions. Another patient with no known history of seizures was
      recorded under similar conditions. RESULTS: The first day following SE was
      associated with markedly abnormal sleep structure, consisting largely of stage 1
      with minimal slow wave or REM sleep. Over 4 days, slow wave and REM returned to
      normal values and no rebound was seen. The control patient demonstrated normal
      sleep parameters for their age, demonstrating that sleep disruption was not due
      to recording conditions alone. CONCLUSIONS: This case demonstrates that sleep
      structure is markedly abnormal following generalized convulsive SE. As sleep may
      serve a restorative function, improving sleep postictally may hasten or improve
      recovery. Larger studies will be required to determine whether this is a common
      finding in such patients, and whether outcome is associated with improved sleep
      quality.

PMID- 14592396
TI  - Low cerebrospinal fluid hypocretin levels found in familial narcolepsy.
AB  - OBJECTIVE: This report describes abnormal hypocretin neurotransmission in a case
      of familial narcolepsy. BACKGROUND: Narcolepsy is a chronic, often-disabling
      central nervous system disorder characterized by excessive daytime sleepiness and
      abnormal rapid eye movement (REM) sleep features including cataplexy, a loss of
      muscle tone triggered by emotion. The cause of human narcolepsy is unknown.
      Several familial cases have been described, but most cases are sporadic (95%). An
      abnormality of hypocretin neurotransmission has been found in a majority of
      sporadic cases. METHODS: Hypocretin-1 levels were measured in the cerebrospinal
      fluid of the narcoleptic proband of a family with several affected members.
      RESULTS: The proband was found to have a hypocretin-1 deficiency. CONCLUSION:
      Abnormal hypocretin neurotransmission is found in familial, as well as sporadic,
      narcolepsy.

PMID- 14592399
TI  - Article reviewed: Decreased sleep quality and increased sleep related movements
      in patients with Tourette's syndrome.

PMID- 14592398
TI  - Article reviewed: Evidence from the waking electroencephalogram that short
      sleepers live under higher homeostatic sleep pressure than long sleepers.

PMID- 14592400
TI  - Article reviewed: Improvement of sleep apnea in patients with chronic renal
      failure who undergo nocturnal hemodialysis.

PMID- 14592401
TI  - Article reviewed: Obesity is a risk factor for asthma and wheeze but not airway
      hyperresponsiveness.

PMID- 14592405
TI  - Coordinated interaction of the vascular and nervous systems: from molecule- to
      cell-based approaches.
AB  - Endothelial cells (ECs) build blood vessels and regulate their plasticity in
      coordination with neurons. Likewise, neurons construct nerves and regulate their
      circuits in coordination with ECs. Blood vessel/nerve interactions, ultimately,
      play essential roles for the neurovascular network and brain function. With
      conventional molecular approaches, such coordinated interaction is likely due to
      complex interplay of neuroangiogenic factors and receptors. Aside from molecular
      regulation of neuroangiogenic factors, currently, cell-based approaches to
      investigate how blood vessels (or nerves) respond to nerves (or blood vessels)
      appropriately in the pathophysiological situation are gradually emerging. In
      order to define responsiveness and flexibility of the neurovascular network in
      response to the local need, the intercellular communication and coordinated
      interaction between the vascular and nervous systems need to be thought as a
      working unit. Based on the scale of the working unit which is in the millimeter
      range with respect to the physical distance of the neurovascular network, we
      propose to use a rather conceptual term "Millibiology". The millibiological
      approach for the coordinated interaction might bring us new paradigm to define
      neurovascular functions in the pathophysiological state.

PMID- 14592406
TI  - pH-dependent aggregation of oligomeric Artocarpus hirsuta lectin on thermal
      denaturation.
AB  - The pH dependence of the activity, aggregation, and secondary structure of
      Artocarpus hirsuta lectin was studied using intrinsic and extrinsic fluorescence,
      light scattering, and circular dichroism. The lectin is more stable in the
      neutral and acidic than in the alkaline pH range, which is also reflected in the
      binding constants of the lectin to methyl alpha-galactopyranoside (me alpha-gal).
      The aggregation of the protein due to heat denaturation is prevented at both
      extremes of pH. The binding of hydrophobic dye to the lectin takes place at pH 1
      2, which increases with increasing temperature. The exposure of hydrophobic
      patches at pH 1 is reversible. The secondary structure of the lectin is intact in
      the pH range of 1-8 and is distorted above pH 9. Aggregation of the protein due
      to heat denaturation is also prevented in the presence of guanidine hydrochloride
      (GdnHCl).

PMID- 14592407
TI  - Functional implication with the metal-binding properties of KChIP1.
AB  - To investigate the metal-binding properties of KChIP1, the interaction of KChIP1
      and mutated KChIP1 with divalent cations (Mg(2+), Ca(2+), Sr(2+), and Ba(2+)) was
      explored by 8-anilinonaphthalene-1-sulfonate (ANS) fluorescence. It showed that
      KChIP1 possessed two types of Ca(2+)-binding sites, high-affinity and low
      affinity Ca(2+)-binding sites. However, only low-affinity-binding site for
      Mg(2+), Sr(2+), and Ba(2+) was observed. The metal-binding properties of KChIP1
      are not appreciably affected after removal of the N-terminal portion and EF-hand
      1. Deleting the EF-hand 4 of KChIP1 abolishes its high-affinity Ca(2+)-binding
      site, but retains the intact low-affinity-binding site for metal ions. A decrease
      in the nonpolarity of ANS-binding site occurs with all mutants. However, the
      binding of ANS with KChIP1 is no longer observed after removal of EF-hands 3 and
      4. Intermolecular interaction assessed by chemical cross-linking suggested that
      KChIP1 had a propensity to form dimer in the absence of metal ions, and a KChIP1
      tetramer was pronouncedly produced in the presence of metal ions. Noticeably, the
      oligomerization state depends on the integrity of EF-hand 4. Taken together, our
      data suggest that EF-hand 4 is of structural importance as well as functional
      importance for fulfilling the physiological function of KChIP1.

PMID- 14592408
TI  - Association between serotonin transporter gene polymorphism and chronic fatigue
      syndrome.
AB  - Interaction between the hypothalamo-pituitary-adrenal axis and the serotonergic
      system is thought to be disrupted in chronic fatigue syndrome (CFS) patients. We
      examined a serotonin transporter (5-HTT) gene promoter polymorphism, which
      affects the transcriptional efficiency of 5-HTT, in 78 CFS patients using PCR
      amplification of the blood genomic DNA. A significant increase of longer (L and
      XL) alleic variants was found in the CFS patients compared to the controls both
      by the genotype-wise and the allele-wise analyses (both p<0.05, by chi(2) test
      and Fisher's exact test). Attenuated concentration of extracellular serotonin due
      to longer variants may cause higher susceptibility to CFS.

PMID- 14592409
TI  - 3-alkoxy-5-isoxazolidinones mimic beta-lactams.
AB  - 3-Alkoxy-5-isoxazolidinones mimic the action of beta-lactams. They bind to the
      penicillin-binding proteins. They inhibit Class A, Class B, and Class D beta
      lactams. They inhibit the growth of Bacillus subtilis. We give a novel synthesis
      for these compounds.

PMID- 14592411
TI  - Interaction of cellular tubulin with Sendai virus M protein regulates
      transcription of viral genome.
AB  - Cellular tubulin has been shown to activate in vitro transcription with Sendai
      virus (SeV) particles. In this study, the molecular basis for the transcriptional
      activation by tubulin was investigated. We showed that tubulin dissociates viral
      matrix (M) protein, which acts as a negative regulator for transcription, from
      viral ribonucleoprotein (RNP) consisting of L, P, N proteins, and the genome RNA.
      Both alpha and beta subunits of human tubulin, which were expressed as GST fusion
      proteins, were found to stimulate viral mRNA synthesis similar to native
      alpha/beta-heterodimer tubulin. Pull-down assay using GST-tubulin subunits
      demonstrated that M protein is released from the RNP as a complex with each
      tubulin subunit. In vitro-binding analyses revealed that M protein directly
      interacts with tubulin as well as microtubules. These findings suggest that
      interaction of M protein with tubulin may have an important role in the
      regulation of SeV transcription.

PMID- 14592410
TI  - Kinesin I and cytoplasmic dynein orchestrate glucose-stimulated insulin
      containing vesicle movements in clonal MIN6 beta-cells.
AB  - Glucose-stimulated mobilization of large dense-core vesicles (LDCVs) to the
      plasma membrane is essential for sustained insulin secretion. At present, the
      cytoskeletal structures and molecular motors involved in vesicle trafficking in
      beta-cells are poorly defined. Here, we describe simultaneous imaging of enhanced
      green fluorescent protein (EGFP)-tagged LDCVs and microtubules in beta-cells.
      Microtubules exist as a tangled array, along which vesicles describe complex
      directional movements. Whilst LDCVs frequently changed direction, implying the
      involvement of both plus- and minus-end directed motors, inactivation of the
      minus-end motor, cytoplasmic dynein, inhibited only a small fraction of all
      vesicle movements which were involved in vesicle recovery after glucose
      stimulated exocytosis. By contrast, selective silencing of the plus-end motor,
      kinesin I, with small interfering RNAs substantially inhibited all vesicle
      movements. We conclude that the majority of LDCV transport in beta-cells is
      mediated by kinesin I, whilst dynein probably contributes to the recovery of
      vesicles after rapid kiss-and-run exocytosis.

PMID- 14592412
TI  - Colocalization of muscle FBPase and muscle aldolase on both sides of the Z-line.
AB  - Previously we have reported that in vitro muscle aldolase binds to muscle FBPase
      [Biochem. Biophys. Res. Commun. 275 (2000) 611-616] which results in the changes
      of regulatory properties of the latter enzyme. In the present paper, the evidence
      that aldolase binds to FBPase in living cell is presented. The colocalization
      experiment, in which aldolase was diffused into skinned fibres that had been pre
      incubated with FBPase, has shown that aldolase in the presence of FBPase binds
      predominantly to the Z-line. The existence of a triple aldolase-FBPase-alpha
      actinin complex was confirmed through a real-time interaction analysis using the
      BIAcore biosensor. The colocalization of FBPase and aldolase on alpha-actinin of
      the Z-line indicates the existence of glyconeogenic metabolon in vertebrates'
      myocytes.

PMID- 14592414
TI  - A trivalent anti-erbB2/anti-CD16 bispecific antibody retargeting NK cells against
      human breast cancer cells.
AB  - Bispecific antibody (BsAb) can physically cross-link immune cells to tumor cells,
      circumventing the proper structures for tumor cell-immune cell interactions and
      activating the cellular cytotoxic mechanisms. The optimal BsAb should target
      tumor cells with high affinity, but activate trigger molecules on cytotoxic cells
      by monovalent binding of Fab fragments. In the present study, a trivalent anti
      erbB2/anti-CD16 BsAb was produced. This BsAb possesses bivalent arms specifically
      binding to the extracellular domain of erbB2 and monovalent Fab fragment
      redirecting NK cells. The recombinant protein could be expressed and purified
      from Escherichia coli as native proteins without refolding. It was fully
      functional in bispecific binding to SKBR3 and NK cells. The molecular size of
      this trivalent BsAb protein is larger than diabody and smaller than whole
      antibody and expected to have advantages for both high penetration of small
      antibody fragments and the slow circulation clearance of whole antibody. This
      novel protein may be an attractive target for further improvement and evaluation.

PMID- 14592413
TI  - Superoxide generation mediated by 8-nitroguanosine, a highly redox-active nucleic
      acid derivative.
AB  - Formation of 8-nitroguanosine may be characterized as nucleic acid modification
      induced by nitric oxide (NO). We show here that 8-nitroguanosine is a highly
      redox-active nucleic acid derivative that strongly stimulated superoxide
      generation from various NADPH-dependent reductases, including cytochrome P450
      reductase and all isoforms of NO synthase. This reaction involves these
      reductases in a redox cycling reaction via single-electron reduction of 8
      nitroguanosine to form 8-nitroguanosine anion radical. One electron is then
      transferred from this radical to molecular oxygen. 8-Nitroguanosine formed in
      vivo may function as a potent redox cofactor that intensifies oxyradical
      generation by various NADPH/reductase-like enzymes and thus participates in
      diverse physiological and pathological events.

PMID- 14592415
TI  - Posttranscriptional regulation of human ABCA7 and its function for the apoA-I
      dependent lipid release.
AB  - ABCA7 is expressed predominantly in myelo-lymphatic tissues or
      reticuloendothelial cells. Physiological role and function of this protein are
      not fully understood. We isolated the full-length cDNA (type I) and a splicing
      variant cDNA (type II) of human ABCA7, and developed monoclonal antibodies
      against extracellular domain (ECD)1 of ABCA7. RT-PCR experiments suggested that
      human ABCA7 gene produced the type II mRNA in a tissue-specific manner.
      Immunostaining revealed that the type I ABCA7, expressed in HEK293 cells, was
      localized to the plasma membrane and ECD1 was exposed to the extracellular space
      as was the case for ABCA1. HEK293 cells expressing type I ABCA7 showed apoA-I
      dependent cholesterol and phospholipid release. In contrast, type II ABCA7
      appeared to be localized mainly in endoplasmic reticulum and did not show apoA-I
      dependent cholesterol and phospholipid release. Alternative splicing could be
      involved in the post-transcriptional regulation of the expression and function of
      human ABCA7.

PMID- 14592416
TI  - Identification of a carcinoembryonic antigen binding protein on monocytes.
AB  - Tumor-associated monocyte/macrophage cells are important stromal components
      involved in tumor development. A protein on human monocyte is identified that
      binds to carcinoembryonic antigen (CEA), a glycoprotein overexpressed in colon
      tumors. This implicates a role for this protein in CEA processing and establishes
      a link between monocytes and colon tumor cells. In vitro uptake of 125I-labeled
      CEA with isolated monocytes showed time and temperature dependence. The binding
      of 125I-CEA was specific and saturable as it could be inhibited by an excess of
      unlabeled CEA. To identify the binding protein on monocyte, we used a
      radiolabeled photoactivable heterobifunctional crosslinking agent and
      demonstrated that CEA reacts with a 115kDa protein as determined by SDS
      polyacrylamide gel electrophoresis and autoradiography. Treatment of human
      monocytes in vitro with CEA resulted in a several fold increase in the production
      of proinflammatory cytokines TNF-alpha, IL-1 beta, and IL-6 compared to untreated
      controls. Binding of CEA to the monocyte protein may have implications in colon
      tumorigenesis.

PMID- 14592417
TI  - CNS melanocortin and leptin effects on stearoyl-CoA desaturase-1 and resistin
      expression.
AB  - The objective of this study was to determine whether centrally administered
      leptin decreased liver and adipose SCD1 expression or adipose resistin
      expression, and whether these effects were mediated by central melanocortin
      receptors. Male Sprague-Dawley rats were injected into the lateral cerebral
      ventricle (i.c.v.) once daily for 4 days with artificial cerebrospinal fluid
      (aCSF, 5 microl), leptin (10 microg) or MTII (0.1 nmol); two other groups were
      pretreated icv with the melanocortin antagonist, SHU9119 (1.0 nmol), followed by
      leptin or MTII. Epididymal and inguinal adipose tissue and liver were collected
      after rats were killed and mRNA expression of SCD1 and resistin was measured.
      Both leptin and MTII reduced SCD1 expression and pretreatment with SHU9119
      reversed their effects. Neither leptin nor MTII affected resistin expression, but
      it was increased by SHU9119. These results show that CNS melanocortin receptors
      are likely mediators of leptin's effects on SCD1 expression in liver and adipose
      tissue, The findings were inconclusive concerning the effects of leptin and
      melanocortins on adipose resistin expression.

PMID- 14592418
TI  - Sphingosine-1-phosphate is a high-affinity ligand for the G protein-coupled
      receptor GPR6 from mouse and induces intracellular Ca2+ release by activating the
      sphingosine-kinase pathway.
AB  - We identified and cloned the mouse orthologue of human GPR6 as a new member of
      the lysophospholipid-receptor family. Sphingosine-1-phosphate (S1P) activated
      GPR6, transiently expressed in frog oocytes or in Chinese hamster ovary (CHO)
      cells, with high specificity and nanomolar affinity. The GPR6 gene was found to
      be located on chromosome 10B1 and a single exon coded for the entire open-reading
      frame. Signal transduction of S1P was inhibited by pertussis toxin, suggesting a
      coupling of GPR6 to an inhibitory G protein. In CHO cells transfected with GPR6,
      the sphingosine-kinase pathway mediated Ca(2+) mobilization from internal stores.
      Apoptotic cell death was induced by serum deprivation or H(2)O(2) treatment and
      was prevented by S1P in GPR6-, but not in vector-transfected CHO cells. The
      antiapoptotic effect of S1P required activation of sphingosine kinase and was
      accompanied by an increase in MAP-kinase phosphorylation.

PMID- 14592419
TI  - Possible involvement of a cyclic AMP-dependent mechanism in PACAP-induced
      proliferation and ERK activation in astrocytes.
AB  - In cultured astrocytes, PACAP activates extracellular signal-regulated kinase
      (ERK) and induces cell proliferation at picomolar concentrations. Here, we
      examined the role of cyclic AMP signaling underlying the effects of PACAP.
      PACAP38 induced accumulation of cyclic AMP in astrocytes at concentrations as low
      as 10(-12)M. PACAP38 (10(-12)-10(-9)M)-stimulated cell proliferation was
      completely abolished by the cyclic AMP antagonist Rp-cAMP, whereas the protein
      kinase A (PKA) inhibitor H89 had no effect. This PACAP38-mediated effect was also
      abolished by the ERK kinase inhibitor PD98059, suggesting the involvement of ERK
      in PACAP-induced proliferation. PACAP38 (10(-12)M)-stimulated phosphorylation of
      ERK lasted for at least 60 min. This effect was completely abolished by Rp-cAMP
      but not by H89. Dibutyryl cyclic AMP maximally stimulated the incorporation of
      thymidine and activation of ERK at 10(-10)M. These results suggest that PACAP
      mediated stimulation of ERK activity and proliferation of astrocytes may involve
      a cyclic AMP-dependent, but PKA-independent, pathway.

PMID- 14592420
TI  - Role of VLDL/chylomicron in amyloid formation in familial amyloidotic
      polyneuropathy.
AB  - We examined the affinity of transthyretin (TTR) for lipoproteins and the effect
      of lipoproteins on TTR-related amyloidogenesis using serum samples from healthy
      volunteers and patients with familial amyloidotic polyneuropathy (FAP)
      ATTRVal30Met. In both volunteers and patients, TTR levels were highest in the
      VLDL fraction containing chylomicrons (VLDL/CM) and next highest in the HDL
      fraction. Levels were lowest in the LDL fraction. Mass spectrometric analyses of
      TTR spectra revealed significant TTR association with VLDL/CM and the levels of
      variant TTR were decreased in the FAP patients. Examination of the affinity of
      wild-type and variant TTRs for lipoprotein via a quartz crystal microbalance
      (QCM) revealed the highest affinity of both proteins for VLDL/CM. In in vitro
      amyloid formation test measured with thioflavin T and electron microscopy, in the
      presence of VLDL/CM, amyloid formation of TTR was enhanced more than in the
      presence LDL or in the absence of lipoprotein species. These results suggest that
      TTR should be highly associated especially with VLDL/CM and amyloidogenicity of
      TTR should be enhanced around the adipocytes.

PMID- 14592421
TI  - Pub, a novel PU.1 binding protein, regulates the transcriptional activity of
      PU.1.
AB  - PU.1 is a member of the Ets family of transcription factors and plays critical
      roles in the development of hematopoietic cells such as macrophages and B cells.
      To elucidate the molecular mechanism(s) underlying the regulation of PU.1
      function, we screened for PU.1 interacting proteins using a yeast two-hybrid
      approach. As a result, a novel PU.1 binding factor, which we termed Pub, was
      isolated. The Pub protein has one B-box zinc finger domain, followed by a coiled
      coil region and a B30.2-like domain, these features being characteristic of the
      tripartite motif (TRIM) family of protein. The PEST domain of PU.1 was found to
      interact with the N-terminal portion of Pub, a region that includes the TRIM
      which is considered to mediate protein-protein interactions. Northern blot and RT
      PCR analyses demonstrated that Pub is predominantly expressed in hematopoietic
      tissues and cells where PU.1 is also expressed. Using a luciferase-based assay,
      we showed that Pub inhibited the transcriptional activity of PU.1. Moreover, the
      B-box zinc finger domain of Pub was critical for this inhibitory activity. These
      data suggest that Pub may be important in regulating the transcriptional activity
      of PU.1.

PMID- 14592422
TI  - The protein tyrosine phosphatase alpha modifies insulin secretion in INS-1E
      cells.
AB  - Increasing evidence indicates a role of insulin signalling for insulin secretion
      from the pancreatic beta-cells. Therefore, regulators of insulin signalling, like
      protein tyrosine phosphatases, could also have an impact on insulin secretion.
      Here, we investigated a possible role of the negative regulator protein tyrosine
      phosphatase alpha (PTP alpha) for insulin secretion. RT-PCR analysis confirmed
      that both splice variants of the extracellular domain of PTP alpha that vary by
      an insert of 9 amino acids are expressed in human islets and insulinoma cells
      (INS-1E, RIN1046-38). Overexpression of the wild type PTP alpha splice variant
      containing the 9 amino acids reduced insulin secretion, as did a mutant form
      unable to bind Grb2 (Tyr798Phe). By contrast, overexpression of a phosphatase
      inactive mutant improved insulin secretion. These data reveal a functional
      relevance of PTP alpha for insulin secretion.

PMID- 14592423
TI  - Human leukocyte formin: a novel protein expressed in lymphoid malignancies and
      associated with Akt.
AB  - The very large family of Formin proteins is involved in processes such as
      morphogenesis, embryonic differentiation, cell polarity, and cytokinesis. A novel
      human gene from the Formin family, denominated human leukocyte formin gene, was
      cloned. The cDNA of the gene was determined to be 3959bp long with an open
      reading frame of 3302bp and computational analysis located this gene on
      chromosome 17, suggesting that it is composed of 27 exons. Northern blot analysis
      revealed a restricted expression of mRNA in the thymus, spleen, and peripheral
      blood leukocytes in normal human tissues. Western blot analysis demonstrated that
      the protein encoded by this gene is overexpressed in lymphoid malignancies;
      cancer cell lines and peripheral blood leukocyte from chronic lymphocytic
      leukemia (CLL) patients. Furthermore, the human leukocyte formin protein was
      observed to associate with Akt, a critical survival regulator in many different
      cell types.

PMID- 14592424
TI  - Chronic interleukin-6 (IL-6) treatment increased IL-6 secretion and induced
      insulin resistance in adipocyte: prevention by rosiglitazone.
AB  - IL-6 has emerged as an important cytokine upregulated in states of insulin
      resistance such as type 2 diabetes. We evaluated the chronic effect of IL-6 on
      insulin signaling in 3T3-F442A and 3T3-L1 adipocytes. First, cells responded to a
      chronic treatment with IL-6 by initiating an autoactivation process that
      increased IL-6 secretion. Second, IL-6-treated adipocytes showed a decreased
      protein expression of IR-beta subunit and IRS-1 but also an inhibition of the
      insulin-induced activation of IR-beta, Akt/PKB, and ERK1/2. Moreover, IL-6
      suppressed the insulin-induced lipogenesis and glucose transport consistent with
      a diminished expression of GLUT4. IL-6-treated adipocytes failed to maintain
      their adipocyte phenotype as shown by the downregulation of the adipogenic
      markers FAS, GAPDH, aP2, PPAR-gamma, and C/EBP-alpha. IL-6 also induced the
      expression of SOCS-3, a potential inhibitor of insulin signaling. Finally, the
      effects of IL-6 could be prevented by rosiglitazone, an insulin-sensitizing
      agent. Thus, IL-6 may play an important role in the set-up of insulin resistance
      in adipose cell.

PMID- 14592425
TI  - Elongation of oligonucleotide primers forming a triple helix on double-stranded
      DNA templates by purified DNA polymerases.
AB  - Current knowledge on the replication of DNA involves enzymatic steps of DNA
      strand separation upon helicase activity, thus enabling the exposed bases of the
      single-stranded DNA to direct the polymerization of complementary nucleotides
      through Watson-Crick base pairing rules by DNA-dependent DNA polymerases. Here,
      we report that oligonucleotide primers (9-11 nt long) bound to the double
      stranded DNA, can be elongated by the T7 and by the Thermus thermophilus DNA
      polymerases and by the Escherichia coli Klenow fragment. A perfectly base-paired
      DNA cannot be used as a template, but a single A/A mismatch located even 5 bp
      upstream from the theoretical 3'-end of the oligonucleotide primer is sufficient
      for DNA elongation by these first two enzymes, while five are required for the
      Klenow fragment. Elongation products from templates containing A/A mismatches at
      different positions revealed similar patterns independently of the positions of
      the A/A mismatches. The sequencing of the elongated products revealed that both
      purine and pyrimidine are incorporated at the pyrimidine-purine-pyrimidine
      transitions of the template strands, probably because of a shift of the primers
      on the double helix template. These data confirm that prokaryotic DNA polymerases
      may accommodate transiently three DNA strands in their catalytic centre. They
      also show for the first time that replication can occur on double-stranded DNA in
      the absence of DNA helicase, when mismatches are present in the vicinity of the
      triple helix initiation complex.

PMID- 14592426
TI  - Real-time molecular beacon NASBA reveals hblC expression from Bacillus spp. in
      milk.
AB  - Nucleic acid sequence-based amplification (NASBA) was applied in combination with
      a fluorescein-conjugated molecular beacon specific for a sequence flanked by
      transcript-specific primers in order to monitor hblC enterotoxin gene expression
      in real-time from milk separately contaminated with Bacillus amyloliquefaciens,
      Bacillus cereus, and Bacillus circulans. Maximal enterotoxin expression was noted
      following 16, 15, and 16 h, respectively, when grown in artificially contaminated
      nonfat dried milk incubated aerobically at 32 degrees C, corresponding to 1.6 x
      10(5), 5 x 10(7), and 9.8 x 10(4)cfu/ml, for B. amyloliquefaciens, B. cereus, and
      B. circulans, respectively. This RNA amplification assay allows for simultaneous
      detection and confirmation of target transcripts in a closed tube format and may
      be performed in a high DNA background. The development of a rapid, sensitive,
      real-time method to quantitate the expression of virulence genes in pathogenic
      spore-formers is useful in shelf life determination of foods and other quality
      assurance measures.

PMID- 14592427
TI  - Functional characterization of human mesenchymal stem cell-derived adipocytes.
AB  - The function of adipocytes derived from human mesenchymal stem cells (hMSC) was
      investigated for the first time in hMSC from fetal liver (FL) and adult bone
      marrow (BM) and compared with preadipocytes from human subcutaneous adipose
      tissue differentiated according to adipocyte-specific protocols. FL- and BM
      derived adipocytes displayed both morphological and functional characteristics of
      mature adipocytes including specific intracellular signaling pathways for tumor
      necrosis factor-alpha, catecholamine-regulated lipolysis as well as secretion of
      adiponectin and leptin. Similar to differentiated preadipocytes, hMSC adipocytes
      displayed lipolytic effects mediated by beta-adrenoceptors and antilipolytic
      effects mediated by the alpha 2A-adrenoceptor (alpha 2A-AR) and expressed
      proteins with a pivotal role in human lipolysis, including beta 2-AR, alpha 2A
      AR, and hormone-sensitive lipase. We conclude that hMSC-derived adipocytes are
      morphologically and functionally similar to preadipocytes and display an intact
      lipolytic signaling pathway and endocrine function. These systems could be of
      great value in adipocyte research as a renewable source of adipocytes.

PMID- 14592428
TI  - Inhibition of hepatitis B virus replication by stably expressed shRNA.
AB  - The major challenges for anti-hepatitis B Virus (HBV) therapy are the low
      efficacy of current drugs and the occurrence of drug resistant HBV mutations. A
      drug with new target sites or independent metabolic pathways may overcome these
      shortcomings. Small interfering RNA (siRNA) offers the possibility of developing
      a new anti-HBV therapy. Here we describe the almost complete inhibition of HBV
      replication by stably expressed 21-mer short hairpin RNAs (shRNA). Besides the
      conventional targets on HBV reverse-transcriptase, we also systemically targeted
      other sites of pregenomic RNA, including direct repeat (DR) elements, S, core,
      and X gene. Our results indicated that shRNAs can serve as efficient alternative
      anti-HBV agents. They can also be used in combination with chemotherapy, because
      they showed better effects on the inhibition of HBV replication due to different
      mechanisms of drug actions.

PMID- 14592429
TI  - Protein disulfide isomerase, a multifunctional protein chaperone, shows copper
      binding activity.
AB  - Protein disulfide isomerase (PDI) is a 55 kDa multifunctional protein of the
      endoplasmic reticulum (ER) involved in protein folding and isomerization. In
      addition to the chaperone and catalytic functions, PDI is a major calcium-binding
      protein of the ER. Although the active site of PDI has a similar motif CXXC to
      the Cu-binding motif in Wilson and Menkes proteins and in other copper
      chaperones, there has been no report on any metal-binding capability of PDI other
      than calcium binding. We present evidence that PDI is a copper-binding protein.
      In the absence of reducing agent freshly reduced PDI can bind a maximum of 4 mol
      of Cu(II) and convert to Cu(I). These bound Cu(I) are surface exposed as they can
      be competed readily by BCS reagent, a Cu(I) specific chelator. However, when the
      binding is performed using the mixture of Cu(II) and 1mM DTT, the total number of
      Cu(I) bound increases to 10 mol/mol, and it is slower to react with BCS,
      indicating a more protected environment. In both cases, the copper-bound forms of
      PDI exist as tetramers while apo-protein is a monomer. These findings suggest
      that PDI plays a role in intracellular copper disposition.

PMID- 14592430
TI  - Epimorphin is involved in differentiation of rat hepatic stem-like cells through
      cell-cell contact.
AB  - Epimorphin, a mesenchymal cell surface-associated molecule, is detected on
      hepatic stellate cells (HSCs) in the liver. Here, we show the involvement of
      epimorphin in differentiation of rat hepatic stem-like cells (HSLCs) through
      contact with HSCs. HSLCs, isolated from adult rats, cultured in stellate cell
      conditioned medium had no phenotypic and morphological changes, whereas HSLCs co
      cultured with HSCs expressed albumin, transferrin, and tyrosine aminotransferase.
      An anti-epimorphin antibody inhibited hepatocytic differentiation of HSLCs in co
      culture. Furthermore, epimorphin induced mRNA expression of albumin, transferrin,
      tyrosine aminotransferase, and gamma-glutamyl transpeptidase with decrease of c
      kit and musashi-1. Morphologically, HSLCs piled up when co-cultured with HSCs,
      which was dramatically inhibited by an anti-epimorphin antibody. HSLCs contact
      with epimorphin started piling up, changed their shape from flat to cuboidal, and
      subsequently developed bile-canaliculi-like structures. In conclusion, epimorphin
      is a factor that induces differentiation of hepatic stem-like cells through
      epithelial-mesenchymal cell contact.

PMID- 14592431
TI  - Stage-specific enhanced expression of mitochondrial fusion and fission factors
      during spermatogenesis in rat testis.
AB  - The mitochondrial fusion factors mitofusins 1 and 2 (Mfn1 and Mfn2) and the
      fission factor dynamin-related protein 1 (Drp1) were found to be highly expressed
      in the pubertal and adult rat testis by Northern blot analysis.
      Immunohistochemistry using specific antisera to Mfn2 and Drp1 revealed a
      pronounced expression of the fusion and fission factors in the round and
      elongating spermatids in the seminiferous tubules, suggesting that at precise
      steps of spermiogenesis (i.e., steps 8-12), spermatid mitochondria are rapidly
      homogenized by frequent fusion and division. Although physiological relevance of
      this phenomenon remains to be clarified, a role is proposed for it as an
      effective means of achieving complete and homogeneous ubiquitination of
      mitochondria, which has recently been demonstrated to be a mechanism for the
      elimination of paternal mitochondria during fertilization, based on the fact that
      the timing of expression of Mfn2 and Drp1 coincides well with that reported for a
      spermatid-specific ubiquitin-conjugating enzyme.

PMID- 14592432
TI  - Atomic resolution structure of obelin: soaking with calcium enhances electron
      density of the second oxygen atom substituted at the C2-position of
      coelenterazine.
AB  - The spatial structure of the Ca(2+)-regulated photoprotein obelin has been solved
      to resolution of 1.1A. Two oxygen atoms are revealed substituted at the C2
      position of the coelenterazine in contrast to the obelin structure at 1.73A
      resolution where one oxygen atom only was disclosed. The electron density of the
      second oxygen atom was very weak but after exposing the crystals to a trace of
      Ca(2+), the electron densities of both oxygen atoms became equally intense. In
      addition, one Ca(2+) was found bound in the loop of the first EF-hand motif. Four
      of the ligands were provided by protein residues Asp30, Asn32, Asn34, and the
      main chain oxygen of Lys36. The other two were from water molecules. From a
      comparison of B-factors for the residues constituting the active site, it is
      suggested that the variable electron densities observed in various photoprotein
      structures could be attributed to different mobilities of the peroxy oxygen
      atoms.

PMID- 14592433
TI  - The Drosophila melanogaster UMP-CMP kinase cDNA encodes an N-terminal
      mitochondrial import signal.
AB  - Drosophila melanogaster cells express a multi-substrate deoxyribonucleoside
      kinase that phosphorylates both purine and pyrimidine deoxyribonucleosides. The
      subsequent phosphorylation step is catalyzed by nucleoside monophosphate kinases.
      We have cloned and characterized the D. melanogaster UMP-CMP kinase (Dm.UMP-CMP
      kinase) to further study the nucleotide metabolizing enzymes in these cells. The
      kinase, encoded by the dak1 gene, was approximately 60% similar to the human UMP
      CMP kinase and predominantly phosphorylated CMP, dCMP, and UMP. Expression
      analysis showed that the Dm.UMP-CMP kinase mRNA was constitutively expressed
      throughout the Drosophila development. The open-reading frame of the Dm.UMP-CMP
      kinase cDNA was extended in the 5'-region compared to UMP-CMP kinases of other
      species. The extended region encoded an N-terminal sequence with properties
      characteristic of a mitochondrial import signal. Expression of the enzyme in
      fusion with the green fluorescent protein verified that the N-terminal signal
      targeted the enzyme to mitochondria. This is the first time a mitochondrial
      pyrimidine nucleoside monophosphate kinase has been cloned from any organism and
      we discuss the implication of this finding for deoxyribonucleoside salvage in
      both Drosophila and other organisms.

PMID- 14592434
TI  - Differential expression of the antioxidant response element within the hNQO1
      promoter in NSCLC versus SCLC.
AB  - To determine whether the human (h) NQO1 (NAD(P)H: quinone oxidoreductase 1) gene
      contains DNA sequences that directly mediate its high and low expression in non
      small cell lung carcinoma (NSCLC) and small cell lung carcinoma (SCLC),
      respectively, a series of deletion constructs spanning up to -4kb of the 5(')
      flanking region of hNQO1 was used in transient transfection assays. The
      antioxidant response element (ARE) was found to be critical to the elevated
      expression of NQO1 in NSCLC. However, the ability of both heterologous and
      deletion promoter constructs to confer ARE responsiveness demonstrated that SCLC
      contains the necessary program/menu of transcription factors responsible to drive
      hNQO1 expression via the ARE. By examining the regulatory region of the hNQO1
      gene, we identified a proximal repressor region between -259 and -131. These
      results provide the first evidence of a proximal repressor region exerting a
      negative role on the regulation of the hNQO1 promoter in SCLC.

PMID- 14592435
TI  - 17 beta-estradiol inhibits cardiac fibroblast growth through both subtypes of
      estrogen receptor.
AB  - The effect of 17 beta-estradiol (E2) on the proliferation of cardiac fibroblasts
      (CFs) remains controversial. This study investigated which subtype of estrogen
      receptor (ER), ER alpha or ER beta, mediated the effect of E2 on CF growth by the
      gain of function analysis using an adenovirus vector. One hundred nanomoles per
      liter of E2 attenuated DNA synthesis by up to 10%, and transactivated the
      estrogen-responsive element determined by luciferase assay in rat neonatal CFs.
      We constructed replication-deficient adenoviruses bearing the coding region of
      human ER alpha, ER beta, or the dominant-negative form of ER beta (designated
      AxCAER alpha, AxCAER beta, and AxCADNER beta, respectively). When CFs were
      infected with AxCAER alpha or AxCAER beta at multiplicity of infection of 20 or
      higher, DNA synthesis was decreased by 50% in response to E2 and the effect was
      abolished by co-infection with AxCADNER beta. Similarly, transcriptional activity
      of ER in CFs infected with AxCAER alpha or AxCAER beta was markedly enhanced and
      co-infection with AxCADNER beta abolished the effects. These results suggest that
      E2 inhibits CF growth and that both ER subtypes mediate the effect comparably and
      redundantly.

PMID- 14592436
TI  - A novel extracellular protein of Streptomyces peucetius binds to daunorubicin but
      does not inhibit the bioactivity of the antibiotic.
AB  - Extracellular proteins of Streptomyces peucetius that bind to a red pigment were
      identified during the course of isolation of mutants defective in daunorubicin
      production. Two pigment-protein complexes were partially purified and this
      complex inhibited the growth of Bacillus subtilis. Routine solvent extraction
      could not separate the pigment from purified pigment-protein complex. Treatment
      with 2% SDS at 100 degrees C followed by solvent extraction also failed to
      separate the protein from the pigment. However, the pigment could be separated
      from the purified pigment-protein complex by heating it in 0.1M HCl at 100
      degrees C followed by solvent extraction. The pigment extracted from the complex
      was analyzed by HPLC and found to be daunorubicin.

PMID- 14592437
TI  - Rapid up-regulation of IRAK-M expression following a second endotoxin challenge
      in human monocytes and in monocytes isolated from septic patients.
AB  - The exposure of human monocytes to the gram-negative endotoxin LPS provokes them
      to enter a transient state in which they are refractory to further stimulation by
      LPS. This phenomenon is known as 'endotoxin tolerance' (ET) and it is
      characterized by a decrease in leukocyte proinflammatory cytokine production in
      response to LPS. In the present study, we have analyzed the expression of IRAK-M
      mRNA and protein in a human model of ET using human monocytes isolated from
      peripheral blood. In these monocyte cultures, IRAK-M mRNA was expressed 6h after
      stimulation with different doses of LPS. However, endotoxin pretreatment induced
      a more immediate up-regulation of IRAK-M gene expression, transcripts appearing
      only one hour after a second LPS-challenge, and the production of high levels of
      IRAK-M protein in these tolerant monocytes. We also analyzed the response of
      monocytes isolated from septic patients within a temporal tolerance timeframe
      when stimulated ex vivo with LPS. In contrast to monocytes from healthy
      volunteers and patients outside of the tolerance timeframe, monocytes from septic
      patients rapidly expressed IRAK-M mRNA when stimulated with LPS ex vivo.
      Moreover, the expression of IRAK-M mRNA was more rapidly induced in the presence
      of a PI3K inhibitor, suggesting a connection between these two kinases. Thus, our
      data indicate that IRAK-M could play a pivotal role in the process of ET in human
      monocytes and provide evidence that PI3K is involved in regulating its
      expression.

PMID- 14592438
TI  - Differential requirement of EGFR signaling for the expression of defective
      proventriculus gene in the Drosophila endoderm and ectoderm.
AB  - A homeobox gene, defective proventriculus (dve), is expressed in various tissues
      including the ventral ectoderm and midgut. Here, we show the expression pattern
      of dve in the ventral ectoderm, in which dve expression is induced by Spitz, a
      ligand for Drosophila epidermal growth factor receptor (EGFR). In spitz mutants,
      dve expression is only lost in the ventral ectoderm and overexpression of Spitz
      induces ectopic dve activation in the ventral ectoderm. Dve expression in the
      middle midgut depends on Decapentaplegic (Dpp) signaling, while expression of a
      dominant-negative form of Drosophila EGFR (DER(DN)) also causes a marked decrease
      in dve expression in the middle midgut. Furthermore, heterozygous mutation of
      thick veins (tkv), a Dpp receptor, strongly enhances the effect of DER(DN). These
      results indicate that EGFR signaling is crucial for dve expression in the ventral
      ectoderm and is required in the middle midgut where it cooperates with Dpp
      signaling.

PMID- 14592439
TI  - Establishment of Alb-DsRed2 transgenic rat for liver regeneration research.
AB  - Because serum albumin is specifically produced by mature hepatocytes, detection
      system of albumin producing cells could be a valuable tool to visualize liver
      regeneration or development. We have developed here an albumin enhancer/promoter
      driven Alb-DsRed2 Tg rat that expresses DsRed2, having liver-specific reporter
      gene expression of red fluorescent protein. To study the transdifferentiation of
      bone marrow cells (BMCs) into albumin producing cells, BMCs from the Alb-DsRed2
      Tg rat were injected into rats having acute liver damage caused by 2
      acetylaminofluorene plus carbon tetrachloride and chronic liver damage by
      repeated administration of CCl(4). DsRed2-positive cells were generated in the
      recipient liver after BMC injection. The number of transdifferentiated DsRed2
      positive cells in chronic liver injury model was increased comparing with that in
      acute injury model. We propose that the Alb-DsRed2 Tg rat is well suited to
      studying in vivo liver regeneration.

PMID- 14592440
TI  - Are hypothalamic neurons transsynaptically connected to porcine adipose tissue?
AB  - Specific anatomical sites and pathways responsible for mediating metabolic and
      neuroendocrine effects of leptin are still poorly understood. Therefore, we
      examined distribution of leptin receptor-containing neurons transsynaptically
      connected with the porcine fat tissue by means of combined viral transneuronal
      tracing and immunohistochemical staining method. Pseudorabies virus (PRV) was
      injected into the perirenal fat tissue in pigs, and after survival periods of 3,
      5, 7, 9, and 11 days, hypothalami were processed immunohistochemically with
      primary antisera against PRV and leptin receptor (OBR). PRV labeled neurons were
      found in paraventricular nucleus (PVN), ventromedial nucleus (VMN), anterior
      hypothalamic area (AHA), preoptic area (PA), arcuate nucleus (ARC), and
      supraoptic nucleus (SON) by nine days after injection of the virus. Double
      labeling immunofluorescence demonstrated that OBR were co-localized in nearly all
      virus-infected neurons. The present results provide the first morphological data
      demonstrating a multisynaptic circuit of neurons of CNS origin which innervates
      porcine fat tissue.

PMID- 14592441
TI  - Oxidized LDLs affect nitric oxide and radical generation in brain endothelial
      cells.
AB  - There is an increase in the generation of reactive oxygen species and nitric
      oxide in the cerebral microcirculation in Alzheimer's disease. The factors that
      cause this increase in oxidative stress have not been identified. Increasing
      evidence suggests that there are common mechanisms in atherosclerosis and
      Alzheimer's disease. The objective of this study was to determine the effects of
      oxidized low density lipoproteins (LDLs) on brain endothelial cells. Cultured rat
      brain endothelial cells were treated with either native LDL (10 microg/ml) or LDL
      oxidized in vitro using 4-hydroxy-2-nonenal (HNE-LDL) (10 microg/ml), for 24h.
      The results showed that HNE-LDL significantly increased production of nitric
      oxide (p<0.01), decreased membrane fluidity (p<0.05), and increased reactive
      oxygen species generation (p<0.01). These data demonstrate that oxidized LDLs
      affect nitric oxide and radical generation in brain endothelial cells and could
      contribute to cerebrovascular dysfunction in Alzheimer's disease.

PMID- 14592442
TI  - The roles of veratryl alcohol and nonionic surfactant in the oxidation of
      phenolic compounds by lignin peroxidase.
AB  - Veratryl alcohol (VA) at higher concentration stimulated the lignin peroxidase
      (LiP)-catalyzed oxidation of phenolic compounds remarkably. This novel phenomenon
      was due to its competition with the phenols for the active site of the enzyme and
      to the high reactivity of the formed cation radical of VA (VA+*) which resulted
      in an additional oxidation of the phenols. The influence of the nonionic
      surfactant Tween 80 on the VA-enhanced LiP-catalyzed oxidation of phenols
      depended on its concentration. At lower concentration it had a small synergetic
      effect but at higher concentration it decreased the initial rate. Studies of the
      capillary electrophoretic behavior of LiP in the presence of Tween 80 showed that
      this effect was caused by the surfactant aggregation on LiP which, at higher
      surfactant concentrations, might impede the access of VA to its binding site on
      LiP and, consequently, the VA+* formation.

PMID- 14592443
TI  - A fusion protein of conotoxin MVIIA and thioredoxin expressed in Escherichia coli
      has significant analgesic activity.
AB  - omega-Conotoxin MVIIA (CTX MVIIA) is a potent and selective blocker of the N-type
      voltage-sensitive calcium channel in neurons. Its analgesic and neuroprotective
      effects may prove useful in treatment of severe pains and ischemia. In this
      paper, we report that a fusion form of CTX MVIIA with thioredoxin (Trx) has
      analgesic function. The DNA fragments were chemically synthesized and ligated to
      form the DNA sequence encoding CTX MVIIA. The synthetic gene was then cloned into
      the expression vector pET-32a(+) and the fusion protein Trx-CTX MVIIA containing
      6x His-tag was purified by one-step metal chelated affinity chromatography
      (MCAC). The purity of final product was over 95% determined by HPLC and the yield
      of the fusion protein was approximately 40 mg/L. The analgesic function was
      detected by using mouse hot-plate assay. After intracranially administering
      fusion protein with the dose of 0.6 mg/kg, marked analgesia was observed. The
      analgesic effects (elevated pain thresholds) were dose-dependent and the
      biological half-life of the fusion toxin was approximately 1.6 h.

PMID- 14592444
TI  - Suppressor mechanism of serum thymic factor on tumor necrosis factor-alpha
      induced apoptosis in the mouse pancreatic beta-cell line.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a cytokine considered to play a key
      role in beta-cell destruction in insulin-dependent diabetes mellitus (IDDM).
      Serum thymic factor (Facteur thymique serique; FTS) is a nonapeptide thymus
      hormone known to inhibit IDDM in a mouse model. In this study, the effect of TNF
      alpha on the murine pancreatic beta-cell line MIN6 was examined. Cell shrinkage
      and detachment were seen in cells treated with 0-50 ng/ml TNF-alpha for 12h.
      Oligonucleosomal DNA fragmentation was determined from non-adherent cells,
      indicating that the TNF-alpha-induced cell destruction was attributed to
      apoptosis. Fragmented DNA was quantified by enzyme-linked immunosorbent assay to
      measure the amount of histone-bound oligonucleosomes. FTS was treated with TNF
      alpha and the percentage of fragmented DNA was analyzed. The data indicate a
      distinct reduction of fragmented DNA at a concentration of 1 ng/ml FTS.
      Expression of TNF receptor I, inducible form of nitric oxide synthase (iNOS),
      interleukin-1 beta-converting enzyme (ICE), Bcl-2, and nuclear factor kappa B (NF
      kappa B) was analyzed by reverse transcriptase-polymerase chain reaction to
      investigate the suppressor mechanism of FTS on TNF-alpha-induced apoptosis. FTS
      treatment suppressed the expression of iNOS and Bcl-2 mRNA in TNF-alpha-treated
      cells. The expression of NF-kappa B mRNA in TNF-alpha-treated cells was enhanced
      after FTS treatment, while that of ICE mRNA did not change in TNF-alpha-treated
      cells with or without FTS treatment. These results suggest that the inhibition of
      MIN6 cell death by FTS on TNF-alpha-induced apoptosis is caused by a negative
      feedback mechanism involving the inhibition of iNOS induction.

PMID- 14592445
TI  - Molecular cloning of a novel human gene encoding histone acetyltransferase-like
      protein involved in transcriptional activation of hTERT.
AB  - To isolate proteins involved in hTERT transcriptional regulation, the HeLa cDNA
      library was screened using the hTERT promoter-based yeast one-hybrid assay. A
      positive clone was rescued and proved to contain an open reading frame and the
      upstream coding sequences were obtained by 5'-RACE. The assembled full cDNA
      consisted of a 2.5 kb reading frame encoding 834 amino acids, in which a
      conserved N-acetyltransferase domain (GNAT family) was searched out in
      bioinformatics, and thus named as hALP (human N-acetyltransferase-like protein,
      GenBank Accession No. AF 489535). The expression of native hALP was identified in
      HeLa cells and proved to distribute in the cellular nucleus. The binding
      potential of hALP to hTERT promoter was confirmed by EMSA and the interacting
      sequence involved to -201- to -56-nt upstream region of the promoter. On
      transfection assay, hALP could obviously transactivate hTERT promoter and
      stimulate endogenous telomerase activity of cells. The analysis on histone
      acetyltransferase showed that hALP could specifically acetylate free histones in
      vitro. The investigation suggested that hALP influences the activity of histone
      acetylation and could up-regulate telomerase activity through transactivation of
      hTERT promoter.

PMID- 14592446
TI  - A novel method to determine thermal transition curves of disulfide-containing
      proteins and their structured folding intermediates.
AB  - The stability of a protein or of its folding intermediates is frequently
      characterized by its resistance to chemical and/or thermal denaturation. The
      folding/unfolding process is generally followed by spectroscopic methods such as
      absorbance, fluorescence, circular dichroism spectroscopy, etc. Here, we
      demonstrate a new method, by using HPLC, for determining the thermal unfolding
      transitions of disulfide-containing proteins and their structured folding
      intermediates. The thermal transitions of a model protein, ribonuclease A (RNase
      A), and a recently found unfolding intermediate of onconase (ONC), des [30-75],
      have been estimated by this method. Finally, the advantages of this method over
      traditional techniques are discussed by providing specific examples.

PMID- 14592447
TI  - bri3, a novel gene, participates in tumor necrosis factor-alpha-induced cell
      death.
AB  - bri3 was identified to be a novel gene up-regulated in TNF-treated cells with
      suppressed subtractive hybridization (SSH) in our laboratory. Previous studies
      showed that overexpression of BRI3 induced apoptosis in L929 cells. To further
      study the function of bri3, we disrupted its expression by expressing bri3
      antisense RNA. The antisense RNA promoted resistance to TNF-induced cell death by
      more than 1000-fold in L929 cells, suggesting the involvement of BRI3 in TNF
      induced cell death in this cell line. Analysis of cell death caused by other
      apoptotic inducers showed that the effect of BRI3 antisense RNA is highly
      specific to TNF-induced cell death. Taken together, bri3 appears to play an
      important role in TNF-induced cell death. Finally, we reported here that BRI3 may
      be localized to lysosome and function through lysosome.

PMID- 14592448
TI  - Small angle X-ray scattering study of the yeast prion Ure2p.
AB  - The GdmCl-induced equilibrium unfolding and dissociation of the dimeric yeast
      prion protein Ure2, and its prion domain deletion mutants Delta 15-42Ure2 and
      90Ure2, was studied by small angle X-ray scattering (SAXS) using synchrotron
      radiation and by chemical cross-linking with dithiobis(succinimidyl propionate)
      (DTSP). The native state is globular and predominantly dimeric prior to the onset
      of unfolding. R(g) values of 32 and 45A were obtained for the native and 5M GdmCl
      denatured states of Delta 15-42Ure2, respectively; the corresponding values for
      90Ure2 were 2-3A lower. SAXS suggests residual structure in the 4M GdmCl
      denatured state and chemical cross-linking detects persistence of dimeric
      structure under these conditions. Hexamers consisting of globular subunits could
      be detected by SAXS at high protein concentration under partially denaturing
      conditions. The increased tendency of partially folded states to form small
      oligomers points to a mechanism for prion formation.

PMID- 14592449
TI  - NF-kappa B-binding activity in an animal diet-induced overweightness model and
      the impact of subsequent energy restriction.
AB  - An impaired immune function linked to obesity has been shown in both human and
      animal studies. The purpose of this work was to analyse the hypothesis that PPAR
      gamma 1 participates in the inhibition of the immune response by affecting the
      DNA-binding ability of the NF-kappa B complex and whether the SREBP-1 expression
      can regulate PPAR gamma 1 expression in spleen. Diet-induced overweight rats
      showed higher PPAR gamma 1 (p<0.05) and lower SREBP-1 (p<0.01) mRNA expression
      levels with an inhibition of the DNA-binding ability of NF-kappa B compared to
      control rats as determined by gel-shift analysis. On the other hand, energy
      restriction decreased SREBP-1 (p<0.01) mRNA expression with no differences in
      PPAR gamma 1 mRNA expression compared to non-restricted rats, which was
      accompanied by a restoration in the DNA-binding ability of NF-kappa B as shown by
      gel-shift analysis. These results suggest that PPAR gamma 1 may be involved in
      the altered immune response through changes in the activity of NF-kappa B.

PMID- 14592450
TI  - Virus particle detection by solid phase immunocapture and atomic force
      microscopy.
AB  - A novel application of atomic force microscopy (AFM) in the rapid, label-free
      detection and identification of viruses is described. Multiplexed, miniaturized
      antibody domains were constructed using "ink-jet" protein arraying technology.
      The solid-phase affinity substrate termed the "ViriChip" was used in the
      immunocapture of bacteriophage fd, canine parvoviruses, and coxsackieviruses and
      analyzed by AFM. Immunocapture was found to be antibody-specific with a
      sensitivity of 10(8)pfu/ml in 30min. Virus binding was found to be linear for
      concentration between 10(8) and 10(10)pfu/ml and did not reach saturation through
      4h.

PMID- 14592451
TI  - Profound negative regulatory effects by resveratrol on vascular smooth muscle
      cells: a role of p53-p21(WAF1/CIP1) pathway.
AB  - We investigated the role of resveratrol, a polyphenol rich in red wine, in cell
      cycle progression and apoptosis of vascular smooth muscle cells (VSMCs).
      Resveratrol inhibited the growth of human aortic VSMCs at concentrations as low
      as 1 microM. This was due to the profound dose-dependent inhibition of DNA
      synthesis by resveratrol. DNA synthesis was more effectively inhibited when cells
      were pretreated with resveratrol. Resveratrol caused a dose-dependent increase in
      intracellular p53 and p21(WAF1/CIP1) levels. At lower concentrations (6.25-12.5
      microM), resveratrol effectively blocked cell cycle progression of serum
      stimulated VSMCs without inducing apoptosis, while the higher concentration of
      resveratrol (25 microM) selectively induced apoptosis in the same VSMCs.
      Intriguingly, however, the same high concentration of resveratrol could not
      induce apoptosis in quiescent VSMCs. These differential biological effects of
      resveratrol on quiescent and proliferating VSMCs suggest that resveratrol may be
      capable of selectively eliminating abnormally proliferating VSMCs of the arterial
      walls in vivo.

PMID- 14592452
TI  - Tissue- and developmental stage-specific activation of alpha 5 and alpha 6(IV)
      collagen expression in the upper gastrointestinal tract of transgenic mice.
AB  - Little is known about mechanisms regulating gene expression for the alpha chains
      of basement membrane type IV collagen, arranged head-to-head in transcription
      units COL4A1-COL4A2, COL4A3-COL4A4, and COL4A5-COL4A6, and implicated broadly in
      genetic diseases. To investigate these mechanisms, we generated transgenic mouse
      lines bearing 5'-flanking sequences of COL4A5 and COL4A6, cloned upstream of a
      lacZ reporter gene. A 3.8-kb fragment upstream of COL4A6 directs reporter gene
      expression in the esophagus, stomach, and duodenum, whereas a 13.8-kb fragment
      directs expression in the esophagus only. A 10.6-kb fragment upstream of COL4A5
      directs expression in the esophagus. Coupled with evidence of long-range
      conservation between human and mouse non-coding sequences, described herein, our
      findings provide the first indication that highly specialized patterns
      characteristic of COL4A5-COL4A6 expression in vivo arise from effects of
      distributed cis-acting regulatory elements on a bidirectional proximal promoter,
      itself transcriptionally competent.

PMID- 14592453
TI  - Characterizing the effects of saturated fatty acids on insulin signaling and
      ceramide and diacylglycerol accumulation in 3T3-L1 adipocytes and C2C12 myotubes.
AB  - A strong correlation between intramyocellular lipid concentrations and the
      severity of insulin resistance has fueled speculation that lipid oversupply to
      skeletal muscle, fat, or liver may desensitize these tissues to the anabolic
      effects of insulin. To identify free fatty acids (FFAs) capable of inhibiting
      insulin action, we treated 3T3-L1 adipocytes or C2C12 myotubes with either the
      saturated FFA palmitate (C16:0) or the monounsaturated FFA oleate (C18:1), which
      were shown previously to be the most prevalent FFAs in rat soleus and
      gastrocnemius muscles. In C2C12 myotubes, palmitate, but not oleate, inhibited
      insulin-stimulation of glycogen synthesis, as well as its activation of
      Akt/Protein Kinase B (PKB), an obligate intermediate in the regulation of
      anabolic metabolism. Palmitate also induced the accrual of ceramide and
      diacylglycerol (DAG), two lipid metabolites that have been shown to inhibit
      insulin signaling in cultured cells and to accumulate in insulin resistant
      tissues. Interestingly, in 3T3-L1 adipocytes, neither palmitate nor oleate
      inhibited glycogen synthesis or Akt/PKB activation, nor did they induce ceramide
      or DAG synthesis. Using myotubes, we also tested whether other saturated fatty
      acids blocked insulin signaling while promoting ceramide and DAG accumulation.
      The long-chain fatty acids stearate (18:0), arachidate (20:0), and lignocerate
      (24:0) reproduced palmitate's effects on these events, while saturated fatty
      acids with shorter hydrocarbon chains [i.e., laurate (12:0) and myristate (14:0)]
      failed to induce ceramide accumulation or inhibit Akt/PKB activation.
      Collectively these findings implicate excess delivery of long-chain fatty acids
      in the development of insulin resistance resulting from lipid oversupply to
      skeletal muscle.

PMID- 14592454
TI  - Involvement of endogenous ceramide in the inhibition of telomerase activity and
      induction of morphologic differentiation in response to all-trans-retinoic acid
      in human neuroblastoma cells.
AB  - In this study, we examined the role of endogenous ceramide in the inhibition of
      telomerase and induction of morphologic differentiation in response to all-trans
      retinoic acid (ATRA) in the SK-N-SH and SK-N-AS human neuroblastoma cell lines.
      The results showed that ATRA inhibited the activity of telomerase significantly
      in a time- and dose-dependent manner, as determined by telomere repeat
      amplification protocol (TRAP). The inhibition of telomerase by ATRA was maximum
      (about 50-80% of untreated controls) at 5-10 microM for 4-8 days. Treatment of
      cells with ATRA (5 microM) also resulted in the inhibition of growth by about 30
      70% after 4 and 8 days of treatment, respectively, which was measured by trypan
      blue exclusion method. Measurement of accumulation of endogenous ceramide by high
      pressure liquid chromatography coupled with mass spectroscopy (LC/MS) showed that
      treatment of cells with ATRA resulted in increased levels of mainly C24:0 and
      C24:1 ceramides at days 2, 4, and 8, respectively. Also, treatment of cells with
      ATRA in the presence of myriocin blocked the accumulation of ceramide
      significantly, and more importantly, presence of myriocin partially prevented the
      inhibition of telomerase. Mechanistically, inhibition of telomerase by endogenous
      ceramide in response to ATRA treatment involves, at least in part, down
      regulation of the expression of telomerase reverse transcriptase (hTERT) mRNA, as
      determined by semi-quantitative RT-PCR, in these cells. In addition, the
      modulation of telomerase activity by ATRA correlated with the induction of
      morphologic differentiation, which was also blocked by myriocin, as determined by
      extension of neurites using phase-contrast microscopy. These results, therefore,
      reveal an important effect of ATRA on telomerase inhibition and induction of
      morphologic differentiation in human neuroblastoma cells. These data also
      demonstrate that endogenous ceramide is one of the upstream regulators of
      telomerase activity in human neuroblastoma cells in response to ATRA.

PMID- 14592456
TI  - Sphingomyelin in the suppression of colon tumors: prevention versus intervention.
AB  - Intestinal cells are regularly exposed to sphingolipid metabolites, i.e.,
      ceramide and sphingoid bases, after hydrolysis of complex sphingolipids from the
      diet. These metabolites are known regulators of cell growth, differentiation, and
      death. Non-pharmacological amounts in the diet have been shown to inhibit early
      stages of chemically induced colon cancer in mice. To distinguish between
      chemopreventive and chemotherapeutic effects of sphingomyelin supplements, mice
      were fed sphingomyelin before and after tumor initiation. Both applications
      drastically reduced tumor formation, without a significant difference among the
      groups, indicating that sphingolipids are as effective in the chemoprevention of
      tumors as in early intervention. The normalization of cell proliferation and rate
      of apoptosis, but not the induction of differentiation, seem to be key players in
      the suppression of tumor formation by dietary sphingomyelin. This may have
      implications for the development of a cancer prevention or treatment strategy
      with sphingolipids as an alternative to conventional drugs.

PMID- 14592455
TI  - Elevation of ceramide in serum lipoproteins during acute phase response in humans
      and mice: role of serine-palmitoyl transferase.
AB  - Recent studies have indicated that ceramide generated in the liver is secreted
      into the bloodstream as component of very-low-density lipoproteins (VLDL) and low
      density lipoproteins (LDL). This manuscript investigates the effect of host acute
      phase response to inflammation on lipoprotein ceramide levels. In humans, two
      different patterns of responses were found. One group of volunteers experienced
      transient increases in serum ceramide at 1.5h after LPS administration. Second
      group showed prolonged increases that reached up to 10-fold above the basal level
      and continued for up to 24h. Increases in ceramide were found only in VLDL and
      LDL particles. LPS administration induced similar increases in mice. These
      increases were accompanied by activation of secreted sphingomyelinase in serum
      and serine-palmitoyl transferase in liver. ASMase knockout mice retained LPS
      induced increases in serum ceramide, thus suggesting that the elevation of VLDL
      and LDL ceramide content is attributed at least in part to activation of de novo
      synthesis of ceramide in the liver.

PMID- 14592457
TI  - Critical residues for the coenzyme specificity of NAD+-dependent 15
      hydroxyprostaglandin dehydrogenase.
AB  - NAD+-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH), a member of the
      short chain dehydrogenase/reductase (SDR) family, is responsible for the
      biological inactivation of prostaglandins. Sequence alignment within SDR coupled
      with molecular modeling analysis has suggested that Gln-15, Asp-36, and Trp-37 of
      15-PGDH may determine the coenzyme specificity of this enzyme. Site-directed
      mutagenesis was used to examine the important roles of these residues. Several
      single mutants (Q15K, Q15R, W37K, and W37R), double mutants (Q15K-W37K, Q15K
      W37R, Q15R-W37K, and Q15R-W37R), and triple mutants (Q15K-D36A-W37R and Q15K-D36S
      W37R) were prepared and expressed as glutathione S-transferase (GST) fusion
      proteins in Escherichia coli and purified by GSH-agarose affinity chromatography.
      Mutants Q15K, Q15R, W37K, W37R, Q15K-W37K, and Q15R-W37K were found to be
      inactive or almost inactive with NADP+ but still retained substantial activity
      with NAD+. Mutant Q15K-W37R and mutant Q15R-W37R showed comparable activity for
      NAD+ and NADP+ with an increase in activity nearly 3-fold over that of the wild
      type. However, approximately 30-fold higher in K(m) for NADP+ than that of the
      wild type enzyme for NAD+ was found for mutants Q15K-W37R and Q15R-W37R.
      Similarly, the K(m) values for PGE(2) of mutants were also shown to increase over
      that of the wild type. Further mutation of Asp-36 to either an alanine or a
      serine of the double mutant Q15K-W37R (i.e., triple mutants Q15K-D36A-W37R and
      Q15K-D36S-W37R) rendered the mutants exhibiting exclusive activity with NADP+ but
      not with NAD+. The triple mutants showed a decrease in K(m) for NADP+ but an
      increase in K(m) for PGE(2). Further mutation at Ala-14 to a serine of a triple
      mutant (Q15K-D36S-W37R) decreased the K(m) values for both NADP+ and PGE(2) to
      levels comparable to those of the wild type. These results indicate that the
      coenzyme specificity of 15-PGDH can be altered from NAD+ to NADP+ by changing a
      few critical residues near the N-terminal end.

PMID- 14592459
TI  - Reversible stepwise negative regulation of CYP1A1 in cultured rat epidermal
      cells.
AB  - When serially passaged, rat epidermal keratinocytes lose the inducibility of
      CYP1A1 gene expression in response to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)
      exposure. In present experiments, loss of CYP1A1 inducibility occurred in a
      stepwise fashion, with some keratinocyte lines progressing through a transiently
      inducible state before becoming completely uninducible. The negative regulation
      occurred at the level of transcription, but the aryl hydrocarbon receptor (AhR)
      pathway appeared fully functional. Transient and stable transfection of
      uninducible cells with reporter constructs containing up to 4.2kb of the CYP1A1
      5'-flanking region resulted in a TCDD-inducible increase in luciferase activity,
      despite no induction of the endogenous gene. Co-treatment with protein synthesis
      inhibitors and TCDD restored responsiveness of the endogenous CYP1A1 gene,
      indicating that the negative regulation was reversible and likely mediated by a
      labile protein. Together, these results demonstrate a novel mechanism of CYP1A1
      transcriptional repression that does not involve any previously reported negative
      regulatory elements for CYP1A1.

PMID- 14592458
TI  - Analysis of recombinant acylated pneumococcal surface adhesin A of Streptococcus
      pneumoniae by mass spectrometry.
AB  - Streptococcus pneumoniae pneumococcal surface adhesin A (PsaA) is a species
      common, immunogenic surface lipoprotein. In this study, the psaA gene was
      expressed as a nonfusion acylated protein in an Escherichia coli expression
      system. Yields of pure recombinant PsaA (rPsaA) were 8-10 mg/liter of
      fermentation culture. Analysis of rPsaA tryptic digests by HPLC-electrospray mass
      spectrometry (MS) confirmed 98% of the expected protein sequence. GC/MS data
      demonstrated very similar acylation of native and rPsaA by C12:0-C22:0 fatty
      acids, with C16 and C18 predominating. Negative ion electrospray MS/MS analysis
      of the rPsaA lipid anchor released by Pronase-E confirmed that the structure was
      based on an N-terminal palmitoylcysteine (Pam(3)Cys). Electrospray MS
      heterogeneity analysis of intact rPsaA indicated that all of the observed
      heterogeneity could be accounted for by the fatty acid distributions. The
      availability of well-characterized rPsaA will facilitate the continued research
      and development of protein-based vaccines for the prevention of pneumococcal
      disease.

PMID- 14592460
TI  - Adhesion and clustering of charge isomers of myelin basic protein at model myelin
      membranes.
AB  - The association of myelin basic protein charge isomers with the lipid part of the
      myelin membrane was investigated at the microscopic (molecular) level in a model
      membrane system, using optical waveguide lightmode spectrometry to determine with
      high precision the kinetics of association and dissociation to planar
      phospholipid membranes under controlled hydrodynamic conditions and over a range
      of protein concentrations. Detailed analysis of the data revealed a rich and
      intricate behaviour and clearly showed that the membrane protein affinity is
      characterized by at least four independent parameters: (i) the association rate
      coefficient characterizing the protein-membrane interaction energy as the protein
      approaches the fluid-membrane interface; (ii) the protein-membrane adhesion,
      i.e., the probability that it will remain at the membrane after arrival; (iii)
      the protein conformation at the membrane; and (iv) the protein's tendency to
      cluster at the membrane. Some of these parameters varied in characteristic ways
      as the bulk solution concentration of the protein was varied, giving further
      clues to the detailed molecular comportment of the protein. The parameters and
      their characteristic variations with bulk concentration were markedly different
      for the different isomers. Implications of these results for neurological
      disorders involving demyelination, such as multiple sclerosis, are discussed.

PMID- 14592461
TI  - Peroxynitrite modulates acidic fibroblast growth factor (FGF-1) activity.
AB  - To establish peroxynitrite (ONOO(-)) as a mediator of acidic fibroblast growth
      factor (FGF-1) function, preparations of recombinant human FGF-1 were treated
      with the pro-oxidant in vitro and identified amino acid modifications were
      correlated with biologic activity. The sequence of FGF-1 amino acid modifications
      induced by increasing concentrations of ONOO(-) was from cysteine oxidation to
      dityrosine formation, and to tyrosine/tryptophan nitration. Low steady-state
      ONOO(-) concentrations (10-50 microM) induced formation of dityrosine, which
      involved less than 0.1% of the total tyrosines. Treatment of FGF-1 with ONOO(-)
      induced a dose-dependent (10-50 microM) loss of sulfhydryl groups that correlated
      with formation of reducible (dithiothreitol, arsenite) FGF-1 aggregates
      containing 50% latent biologic activity. Treatment with 0.1-0.5mM ONOO(-) induced
      increasing formation of non-reducible, inactivated FGF-1 structures. Combination
      of real-time spectral analysis and electrospray mass spectroscopy revealed that
      six residues (Y29, Y69, Y108, Y111, Y139, and W121) were nitrated by ONOO(-).
      ONOO(-) treatment (0.1mM) of an active FGF-1 mutant (cysteines converted to
      serines) induced dose-dependent, non-reversible inhibition of biologic activity
      that correlated with nitration of Y108 and Y111, both of which reside within a
      conserved domain encompassing the putative FGF-1 receptor binding site.
      Collectively, these observations predict a role for low levels of ONOO(-) during
      secretion of FGF-1 as an extracellular complex containing latent biologic
      activity. High steady-state levels of ONOO(-) may induce extensive cysteine
      oxidation, critical tyrosine nitration, and non-reversible inactivation of FGF-1,
      a potential inhibitory feedback mechanism restoring cellular homeostatis during
      the resolution of inflammation and repair.

PMID- 14592462
TI  - Backdoor phosphorylation of basolateral plasma membranes of small intestinal
      epithelial cells: characterization of a furosemide-induced phosphoprotein related
      to the second sodium pump.
AB  - Enterocyte has two different Na+-stimulated ATPases, the ouabain-sensitive Na+/K+
      ATPase and a furosemide-inhibitable Na+ ATPase. To identify the polypeptide
      associated with the Na+-ATPase, 32Pi phosphorylation into basolateral membranes
      of enterocyte was investigated. Both, ouabain and furosemide induced Mg2+
      dependent, vanadate-sensitive 32Pi incorporation into a 100kDa polypeptide. K(m)
      for Pi was 17.7+/-1.82 microM and 16.8+/-0.69 microM for ouabain-induced and
      furosemide-induced phosphorylation, respectively. K(m) for furosemide was 1.3+/
      0.21 mM. Furosemide-induced 32Pi incorporation was sensitive to alkaline pH and
      hydroxylamine suggesting an acyl-phosphate bond. Na+ and K+ inhibited 32Pi
      incorporation induced by ouabain. In contrast, Na+ stimulated furosemide-induced
      phosphorylation with a K(m) of 16.5+/-5.59 mM while K+ had no effect. Purified
      Na+/K+ ATPase only presented ouabain-induced phosphoprotein, indicating that
      furosemide-induced phosphorylation is not related to this enzyme and appears to
      correspond to a new member of P-type ATPases associated with the second Na+ pump.

PMID- 14592463
TI  - Superoxide anion generation by the cytochrome bc1 complex.
AB  - We have measured the rates of superoxide anion generation by cytochrome bc(1)
      complexes isolated from bovine heart and yeast mitochondria and by cytochrome
      bc(1) complexes from yeast mutants in which the midpoint potentials of the
      cytochrome b hemes and the Rieske iron-sulfur cluster were altered by mutations
      in those proteins. With all of the bc(1) complexes the rate of superoxide anion
      production was greatest in the absence of bc(1) inhibitor and ranged from 3% to
      5% of the rate of cytochrome c reduction. Stigmatellin, an inhibitor that binds
      to the ubiquinol oxidation site in the bc(1) complex, eliminated superoxide anion
      formation, while myxothiazol, another inhibitor of ubiquinol oxidation, allowed
      superoxide anion formation at a low rate. Antimycin, an inhibitor that binds to
      the ubiquinone reduction site in the bc(1) complex, also allowed superoxide anion
      formation and at a slightly greater rate than myxothiazol. Changes in the
      midpoint potentials of the cytochrome b hemes had no significant effect on the
      rate of cytochrome c reduction and only a small effect on the rate of superoxide
      anion formation. A mutation in the Rieske iron-sulfur protein that lowers its
      midpoint potential from +285 to +220 mV caused the rate of superoxide anion to
      decline in parallel with a decline in cytochrome c reductase activity. These
      results indicate that superoxide anion is formed by similar mechanisms in
      mammalian and yeast bc(1) complexes. The results also show that changes in the
      midpoint potentials of the redox components that accept electrons during
      ubiquinol oxidation have only small effects on the formation of superoxide anion,
      except to the extent that they affect the activity of the enzyme.

PMID- 14592464
TI  - Mechanism for the paradoxical inhibition and stimulation of calcineurin by the
      immunosuppresive drug tacrolimus (FK506).
AB  - We examined the paradoxical inhibition and stimulation of calcineurin, the
      calcium-activated protein phosphatase, using the drug FK506 (tacrolimus) which
      acts as a complex together with its binding protein; the complex is designated
      here as FKC. We reproduced FKC inhibition with RIIp, a phosphorylated peptide
      substrate, and FKC stimulation with p-nitrophenylphosphate (pNPP) as substrate.
      The presence of RIIp in the pNPP assay caused inhibition. Yet, under these
      conditions, FKC still stimulated pNPP dephosphorylation to the same extent. The
      effects of Mn2+ were strikingly different for the two substrates when calcineurin
      was measured under otherwise identical conditions: Mn2+ stimulated pNPP
      dephosphorylation several fold, but only stimulated RIIp dephosphorylation by
      about 50%. When Pi was used as product inhibitor, FKC stimulation, but not
      calmodulin stimulation, was attenuated. We conclude that FKC enhances substrate
      binding to the enzyme. This would lead to inhibition with RIIp, known to bind
      calcineurin tightly, but stimulation with pNPP, known to bind calcineurin weakly.
      The result not only resolves the paradox but also elucidates the mechanism of
      action for this class of immunosuppressive drugs.

PMID- 14592465
TI  - Sigma-class glutathione transferase from Xenopus laevis: molecular cloning,
      expression, and site-directed mutagenesis.
AB  - The structural gene for glutathione transferase (XlGSTS1-1) in the amphibia
      Xenopus laevis has been cloned from an embryo library and its nucleotide sequence
      has been determined. Open reading frame analysis indicated that xlgsts1 gene
      encodes the smallest protein of sigma class GST so far identified as being
      composed of only 194 amino acid residues. The recombinant XlGSTS1-1 shows a
      narrow range of substrate specificity as well as a significantly lower 1-chloro
      2,4-dinitrobenzene conjugation capacity than that of squid sigma class GST. To
      compare the structural and functional differences between the squid and amphibian
      enzymes, several site-specific mutations were introduced in XlGSTS1-1, i.e.,
      Ser100Asn, Phe102Tyr, Trp143Leu, Phe146Leu, and Trp148Cys. The results obtained
      indicate that Trp143 and Trp148 are more important determinants for the
      structural stability of XlGSTS1-1 rather than for its substrate specificity.

PMID- 14592466
TI  - Multiple cellular consequences of isocitrate dehydrogenase isozyme dysfunction.
AB  - To probe the functions of multiple forms of isocitrate dehydrogenase in
      Saccharomyces cerevisiae, mutants lacking three of the isozymes were constructed
      and analyzed. Results show that, while the mitochondrial NAD+-dependent enzyme,
      IDH (composed of Idh1p and Idh2p subunits) is not the major contributor to total
      isocitrate dehydrogenase activity under any growth condition, loss of IDH
      produces the most dramatic growth phenotypes. These include reduced growth in the
      absence of glutamate, as well as an increase in expression of Idp2p (the
      cytosolic NADP+-dependent enzyme) under some growth conditions. In this study, we
      have focused on another phenotype associated with loss of IDH, an elevated
      frequency of petite mutations indicating loss of functional mtDNA. Using mutant
      forms of IDH with altered active site residues, a correlation was observed
      between the high frequency of petite mutations and the loss of catalytic
      activity. Loss of Idp1p (the mitochondrial NADP+-dependent enzyme) and Idp2p
      contributes to the loss of functional mtDNA, but only in an IDH dysfunctional
      background. Surprisingly, overexpression of Idp1p, but not of Idp2p, was found to
      result in an elevated petite frequency independent of the functional state of
      IDH. This is the first phenotype associated with altered Idp1p. Finally,
      throughout this study we examined effects of loss of mitochondrial citrate
      synthase (Cit1p) on isocitrate dehydrogenase mutants, since defects in the CIT1
      gene were previously shown to enhance growth of IDH dysfunctional strains on
      nonfermentable carbon sources. Loss of Cit1p was found to suppress the petite
      phenotype of strains lacking IDH, suggesting that these phenotypes may be linked.

PMID- 14592467
TI  - Hydrolysis of 4-HPR to atRA occurs in vivo but is not required for retinamide
      induced apoptosis.
AB  - The retinamide, N-(4-hydroxyphenyl)retinamide (4-HPR), has shown promising anti
      tumor activity, but it is unclear whether this compound is hydrolyzed to all
      trans retinoic acid (atRA) and if so, whether this plays any role in its
      chemotherapeutic activity. To address this issue, the ability of 4
      hydroxybenzylretinone (4-HBR), a carbon-linked analog of 4-HPR, to support growth
      in vitamin A-deficient (VAD) animals and to activate an atRA-responsive gene in
      vivo was compared to 4-HPR and atRA. Further, the non-hydrolyzable 4-HBR analog
      was used to determine whether the presence of the labile amide linkage in 4-HPR
      is essential for the induction of apoptosis in cultured MCF-7 breast cancer
      cells. Studies in VAD rats showed that 4-HPR, like atRA, supports animal growth
      and induces CYP26B1 mRNA expression in lung whereas 4-HBR does not. Analysis of
      plasma from 4-HPR- and atRA-treated VAD animals revealed the presence of atRA
      whereas it was not detected in plasma from animals given 4-HBR. To determine
      whether hydrolysis to atRA is necessary for apoptosis induced by 4-HPR in MCF-7
      breast cancer cells, morphological and biochemical assays for apoptosis were
      performed. 4-HBR, like 4-HPR, induced apoptosis in MCF-7 cells. Apoptosis was not
      induced even at high concentrations of atRA, showing that 4-HPR and 4-HBR act in
      cells via a distinct signaling pathway. These results show that although limited
      hydrolysis of 4-HPR occurs in vivo, the ability to liberate atRA is not required
      for these 4-hydroxyphenyl retinoids to induce apoptosis in MCF-7 breast cancer
      cells. Thus the non-hydrolyzable analog, 4-HBR, may have significant therapeutic
      advantage over 4-HPR because it does not liberate atRA that can contribute to the
      adverse side effects of drug administration in vivo.

PMID- 14592468
TI  - The effect of conserved residue charge reversal on the folding of recombinant non
      phosphorylated human beta-casein.
AB  - A short stretch of 13 amino acids in the central portion of human beta-casein
      contains four positively charged conserved residues, three Lys and one Arg. We
      changed these individually to Glu, reversing their charge, and compared the
      resulting recombinant proteins to the wild-type recombinant, monitoring thermal
      aggregation with turbidity as well as using the fluorescence of the intrinsic
      Trp, of hydrophobically bound ANS and fluorescence resonance energy transfer from
      Trp to ANS to detect differences in structure. The results demonstrate the need
      to maintain the actual or functional identity of these conserved charged amino
      acid residues in order to attain the protein folding and functional properties of
      the wild-type human beta-casein molecule. They emphasize the probability that
      native human beta-casein has a unique folding pattern that is important for its
      function of suspending minerals and delivering the protein and minerals to the
      neonate in a readily ingestible form.

PMID- 14592470
TI  - Chemical synthesis of S-ribosyl-L-homocysteine and activity assay as a LuxS
      substrate.
AB  - Bacterial quorum sensing is mediated by autoinducers, small signaling molecules
      generated by bacteria. It has been proposed that the LuxS enzyme converts S
      ribosyl-L-homocysteine to 4,5-dihydroxy-2,3-pentanedione, the precursor of
      autoinducer 2 (AI-2). We report here a chemical synthesis of S-ribosyl-L
      homocysteine and its analogue using Mitsunobu coupling. Chemically synthesized
      ribosylhomocysteine has been confirmed as a substrate for LuxS in both an enzyme
      assay and a whole cell quorum sensing assay. The chemical entities of products
      from the LuxS reaction were also established. Several ribosylhomocysteine
      analogues have been tested as LuxS inhibitors.

PMID- 14592471
TI  - Naringenin derivatives as anti-atherogenic agents.
AB  - Two classes of naringenin derivatives were evaluated for anti-atherogenic
      activity. Naringenin 7-O-oleic ester (2) and naringenin 7-O-cetyl ether (3)
      inhibited the formation of aortic atherosclerotic lesions in high cholesterol-fed
      rabbits.

PMID- 14592472
TI  - Green tea catechins as a BACE1 (beta-secretase) inhibitor.
AB  - In the course of searching for BACE1 (beta-secretase) inhibitors from natural
      products, the ethyl acetate soluble fraction of green tea, which was suspected to
      be rich in catechin content, showed potent inhibitory activity. (-)
      Epigallocatechin gallate, (-)-epicatechin gallate, and (-)-gallocatechin gallate
      were isolated with IC(50) values of 1.6 x 10(-6), 4.5 x 10(-6), and 1.8 x 10(-6)
      M, respectively. Seven additional authentic catechins were tested for a
      fundamental structure-activity relationship. (-)-Catechin gallate, (-)
      gallocatechin, and (-)-epigallocatechin significantly inhibited BACE1 activity
      with IC(50) values of 6.0 x 10(-6), 2.5 x 10(-6), and 2.4 x 10(-6) M,
      respectively. However, (+)-catechin, (-)-catechin, (+)-epicatechin, and (-)
      epicatechin exhibited about ten times less inhibitory activity. The stronger
      activity seemed to be related to the pyrogallol moiety on C-2 and/or C-3 of
      catechin skeleton, while the stereochemistry of C-2 and C-3 did not have an
      effect on the inhibitory activity. The active catechins inhibited BACE1 activity
      in a non-competitive manner with a substrate in Dixon plots.

PMID- 14592473
TI  - Heterocyclic ketones as inhibitors of histone deacetylase.
AB  - Several heterocyclic ketones were investigated as potential inhibitors of histone
      deacetylase. Nanomolar inhibitors such as 22 and 25 were obtained, the anti
      proliferative activity of which were shown to be mediated by HDAC inhibition.

PMID- 14592474
TI  - Synthesis of linked carbohydrates and evaluation of their binding for 16S RNA by
      mass spectrometry.
AB  - A library of linked molecules were synthesized from the common sugar moieties
      existing in the natural amino glycosides. These linked molecules were screened
      against bacterial 16S RNA for their binding affinity using a mass spectrometry
      based technology. Some of these compounds exhibited low micromolar affinity and
      could serve as leads for further development as antibacterial agents.

PMID- 14592475
TI  - Structural analysis of the immature form of the GFP homologue DsRed.
AB  - The crystal structures of DsRed have shown that it contains an unusual non
      proline containing cis peptide linkage. We have shown that it is also present in
      the precyclized immature form of DsRed, thereby eliminating the possibility that
      cis/trans isomerization drives the formation of the acylimine, which is
      responsible for DsRed's red fluorescence. Two mechanisms have been proposed for
      chromophore formation in green fluorescent protein (GFP), a "reduced" and an
      "oxidized" mechanism. DsRed adopts a tight turn conformation, such as that found
      in GFP, in the immature intermediate proposed in the oxidized mechanism, but not
      in the one predicted by the reduced mechanism.

PMID- 14592476
TI  - Triethylene tetraamine: a novel telomerase inhibitor.
AB  - Telomerase inhibition can be achieved by stabilization of G-quadruplex structure.
      Triethylene tetraamine, a small linear molecule, has been identified as a potent
      telomerase inhibitor. It stabilizes both intra- and inter-molecular G
      quadruplexes and shows a good differential between potent telomerase inhibition
      and acute cytotoxicity.

PMID- 14592477
TI  - Synthesis of 17beta-estradiol platinum(II) complexes: biological evaluation on
      breast cancer cell lines.
AB  - The synthesis of a novel series of 17beta-estradiol-linked platinum(II) complexes
      is described. The new molecules are linked with an alkyl chain at position
      16alpha of the steroid nucleus and bear a 16beta-hydroxymethyl side chain. They
      are made from estrone in five chemical steps with an overall yield exceeding 28%.
      The biological activity of these compounds was evaluated in vitro on estrogen
      dependent and independent (ER+ and ER-) human breast cancers. The derivatives
      incorporating a 2-(2'-aminoethyl)pyridine ligand displayed good activity against
      the cell lines particularly when the connecting arm is 10 carbon atoms long.

PMID- 14592478
TI  - Novel radiosynthesis of PET HSV-tk gene reporter probes [18F]FHPG and [18F]FHBG
      employing dual Sep-Pak SPE techniques.
AB  - Positron emission tomography (PET) herpes simplex virus thymidine kinase (HSV-tk)
      gene reporter probes 9-[(3-[(18)F]fluoro-1-hydroxy-2-propoxy)methyl]guanine
      ([(18)F]FHPG) and 9-(4-[(18)F]fluoro-3-hydroxymethylbutyl)guanine ([(18)F]FHBG)
      were prepared by nucleophilic substitution of the appropriate tosylated
      precursors with [(18)F]KF/Kryptofix 2.2.2 followed by a quick deprotection
      reaction and purification with a simplified dual Silica Sep-Pak solid-phase
      extraction (SPE) method in 15-30% radiochemical yield.

PMID- 14592480
TI  - Synthesis and biological activities of novel 4"-alkylidene avermectin
      derivatives.
AB  - Horner-Emmons reaction of 4"-dehydro-5-O-TBDMS-avermectin B(1a) with a variety of
      phosphorus ylides using LHMDS gave novel 4"-alkylidene avermectin derivatives in
      high yields. Further modifications led to derivatives bearing diverse functional
      groups. The new avermectin derivatives showed potent growth inhibitory activity
      against Artemia salina and Caenorhabditis elegans.

PMID- 14592479
TI  - Advances toward new antidepressants beyond SSRIs: 1-aryloxy-3-piperidinylpropan-2
      ols with dual 5-HT1A receptor antagonism/SSRI activities. Part 3.
AB  - A series of 1-aryloxy-3-piperidinylpropan-2-ols possessing potent dual 5-HT(1A)
      receptor antagonism and serotonin reuptake inhibition was discovered.
      Modification of potential metabolic sites of 1-(1H-indol-4-yloxy)-3-(4
      benzo[b]thiophen-2-ylpiperidinyl)propan-2-ols further improved the in vitro
      binding affinities and functional antagonism.

PMID- 14592481
TI  - Identification of a monoacid-based, cell permeable, selective inhibitor of
      protein tyrosine phosphatase 1B.
AB  - Monoacid-based PTP1B inhibitors with improved physiochemical properties have been
      investigated. A (2-hydroxy-phenoxy) acetic acid-based phosphotyrosyl mimetic has
      been linked with an optimized second arylphosphate binding site ligand to produce
      compound 20 with low micromolar potency against PTP1B, good selectivity over
      TCPTP (20-fold) and high cell permeability in the Caco-2 system.

PMID- 14592482
TI  - Design and synthesis of orally active inhibitors of TNF synthesis as anti
      rheumatoid arthritis drugs.
AB  - A novel series of TNF inhibitors was identified based on the screening of
      existing MMP inhibitor libraries. Further SAR optimization led to the discovery
      of a novel lead compound. Its synthesis, efficacy in experimental animal models,
      and pharmacokinetic data are discussed.

PMID- 14592483
TI  - Synthesis and DNA-binding affinity of A-C8/C-C2 alkoxyamido-linked pyrrolo[2,1
      c][1,4]benzodiazepine dimers.
AB  - The synthesis of new A-C8/C-C2 alkoxyamido-linked pyrrolo[2,1-c][1,4]
      benzodiazepine dimers have been described in this report. These dimers exhibit
      significant DNA-binding ability with moderate anticancer activity.

PMID- 14592484
TI  - Synthesis of double-headed 2-5A-antisense chimeras and their ability to activate
      human RNase L.
AB  - The synthesis of a novel 2-5A-antisense chimera having two molecules of a 2-5A
      tetramer at the 5'-terminus of the antisense moiety with a 2-(hydroxymethyl)-1,3
      propanediol linker is described. The ability of the synthesized 2-5A antisense
      chimeras to activate RNase L was estimated by monitoring the cleavage of a target
      RNA by the activated RNase L. The double-headed 2-5A-antisense chimera linked
      with two molecules of a butanediol linker more efficiently cleaved the target RNA
      as compared with the single-headed 2-5A-antisense chimera and the double-headed 2
      5A-antisense chimera linked with a molecule of the butanediol linker.

PMID- 14592485
TI  - Synthesis of 2-fluoronoraristeromycin and its inhibitory activity against
      Plasmodium falciparum S-adenosyl-L-homocysteine hydrolase.
AB  - Palladium-coupling reaction of (1S, 4R)-cis-4-acetoxy-2-cyclopenten-1-ol with
      sodium salt of 2-fluoroadenine resulted in the formation of (1S,4R)-4-(6-amino-2
      fluoro-9H-purin-9-yl)cyclopent-2-en-1-ol. Subsequent oxidation was carried out
      with osmium tetraoxide (OsO(4)) in the presence of 4-methylmorpholine N-oxide
      (NMO) to give 2-fluoronoraristeromycin, possessing significant inhibitory
      activity against recombinant Plasmodium falciparum SAH hydrolase.

PMID- 14592486
TI  - Novel DNA/polymer conjugate for intelligent antisense reagent with improved
      nuclease resistance.
AB  - Antisense technology provides an effective strategy to inhibit synthesis of the
      gene product. We prepared a novel antisense reagent comprised of
      oligodeoxynucleotides (ODN) and a thermo responsive polymer, poly(N
      isopropylacrylamide) (PNIPAAm). The conjugate inhibited gene expression in a dose
      dependent manner. The ODN-PNIPAAm conjugate demonstrated excellent resistance to
      S1 nuclease. In particular, PNIPAAm-modified antisense ODN at the 3',5'-ends of
      the ODN provided complete resistance against nuclease at 37 degrees C, which is
      above the phase transition temperature of the PNIPAAm side chain. These
      characteristics of the conjugate suggest it may have potential for use in a new
      gene delivery system as part of an antisense strategy.

PMID- 14592487
TI  - Dehydroabietic acid derivatives as a novel scaffold for large-conductance calcium
      activated K+ channel openers.
AB  - We found that the dehydroabietic acid structure is a new scaffold for chemical
      modulators of large-conductance calcium-activated K+ channels (BK channels).
      Structure-activity relationship (SAR) studies of the dehydroabietic acid
      derivatives and related non-aromatic compounds such as pimaric acid revealed the
      importance of the carboxyl functionality and an appropriate hydrophobic moiety of
      the molecules for BK channel-opening ability.

PMID- 14592488
TI  - Synthesis of novel fluorescent probes for the molecular chaperone Hsp90.
AB  - Heat shock protein 90 (Hsp90) is a molecular chaperone necessary for maintaining
      oncogenic transformation. There is substantial interest in developing novel
      agents that bind to the N-terminal of the chaperone. Here we report the synthesis
      and characterization of two fluorescent Hsp90 inhibitors and probe their use in
      an Hsp90 fluorescent polarization assay.

PMID- 14592489
TI  - SAR of 3,4-dihydropyrido[3,2-d]pyrimidone p38 inhibitors.
AB  - Development for a class of potent 3,4-dihydropyrido(3,2-d)pyrimidone inhibitors
      of p38a MAP kinase is described. Modification of N-1 aryl and C-6 arylsulfide in
      3,4-dihydropyrido(3,2-d)pyrimidone analogues for the interaction with the
      hydrophobic pockets in p38 active site is also discussed.

PMID- 14592490
TI  - Benzyl vinylogous amide substituted aryldihydropyridazinones and
      aryldimethylpyrazolones as potent and selective PDE3B inhibitors.
AB  - Aryldihydropyridazinones and aryldimethylpyrazolones with 2-benzyl vinylogous
      amide substituents have been identified as potent PDE3B subtype selective
      inhibitors. Dihydropyridazinone 8a (PDE3B IC(50)=0.19 nM, 3A IC(50)=1.3 nM) was
      selected for in vivo evaluation of lipolysis induction, metabolic rate increase,
      and cardiovascular effects.

PMID- 14592491
TI  - Identifying inhibitors of the SARS coronavirus proteinase.
AB  - The Severe Acute Respiratory Syndrome (SARS) is a serious respiratory illness
      that has recently been reported in parts of Asia and Canada. In this study, we
      use molecular dynamics (MD) simulations and docking techniques to screen 29
      approved and experimental drugs against the theoretical model of the SARS CoV
      proteinase as well as the experimental structure of the transmissible
      gastroenteritis virus (TGEV) proteinase. Our predictions indicate that existing
      HIV-1 protease inhibitors, L-700,417 for instance, have high binding affinities
      and may provide good starting points for designing SARS CoV proteinase
      inhibitors.

PMID- 14592492
TI  - Rational design of antimicrobial agents: antifungal activity of alk(en)yl
      dihydroxybenzoates and dihydroxyphenyl alkanoates.
AB  - A homologous series (C3-C14) of each alkyl 3,4- and 3,5-dihydroxybenzoates, and
      3,4- and 3,5-dihydroxyphenyl alkanoates exhibit similar antifungal activity
      against Saccharomyces cerevisiae. Their nonyl derivatives exhibit the most potent
      antifungal activity against this yeast with the minimum fungicidal concentration
      (MFC) in the range between 12.5 and 50 microg/mL. In addition, various 3,4
      dihydroxybenzoates, possessing different side chains, namely unsaturated,
      branched and alicyclic were synthesized and their activity was compared.

PMID- 14592494
TI  - Pyridone-containing farnesyltransferase inhibitors: synthesis and biological
      evaluation.
AB  - Farnesyltransferase inhibitors (FTIs) have been developed as potential anti
      cancer agents due to their efficacy in blocking malignant growth in a variety of
      murine models of human tumors. To that end, we have developed a series of
      pyridone farnesyltransferase inhibitors with potent in vitro and cellular
      activity. The synthesis, SAR and biological properties of these compounds will be
      discussed.

PMID- 14592493
TI  - 2-arylaminothiazoles as high-affinity corticotropin-releasing factor 1 receptor
      (CRF1R) antagonists: synthesis, binding studies and behavioral efficacy.
AB  - 2-arylamino-4-trifluoromethyl-5-aminomethylthiazoles represent a novel series of
      high-affinity corticotropin releasing factor-1 receptor (CRF(1)R) antagonists
      that are prepared in three steps in good overall yields. Herein, we report
      binding SAR as well as anxiolytic activity of an exemplary compound (7a, K(i)=8.6
      nM) in a mouse canopy model.

PMID- 14592495
TI  - Discovery and initial SAR of 2-amino-5-carboxamidothiazoles as inhibitors of the
      Src-family kinase p56(Lck).
AB  - A novel series of 2-amino-5-carboxamidothiazoles were identified as inhibitors of
      Lck. Structure-activity studies demonstrate the structural requirements for
      potent Lck activity. Cyclopropylamide 11d is a potent Lck inhibitor having sub
      micromolar activity in a PBL proliferation assay.

PMID- 14592496
TI  - 11,12-epoxyeicosatrienoic acid (11,12-EET): structural determinants for
      inhibition of TNF-alpha-induced VCAM-1 expression.
AB  - A series of 11,12-EET analogues were synthesized and compared using a human
      endothelial cell based TNF-alpha-induced VCAM-1 expression assay. The resulting
      data were used to map a putative recognition/binding domain for 11,12-EET.

PMID- 14592498
TI  - Studies of molecular mechanism of tenofovir against 3TC- and AZT-resistance
      mutant HIV-1 reverse transcriptase.
AB  - Molecular modeling study shows that conformational flexibility of acyclic nature
      of TFV provides energetically indistinguishable multiple conformations, which do
      not experience the cross-resistance conferred by mutant RTs. TFV-DP is located
      far away from the bulky side chain of Val184 in M184V RT and tenofovir is readily
      translocated without steric hindrance with Asp185 after incorporation into the
      growing primer chain complexed with AZT-resistant RT.

PMID- 14592499
TI  - Isotopically labeled crosslinking reagents: resolution of mass degeneracy in the
      identification of crosslinked peptides.
AB  - Mass spectrometry in three dimensions (MS3D) is a newly developed method for the
      determination of protein structures involving intramolecular chemical
      crosslinking of proteins, proteolytic digestion of the resulting adducts,
      identification of crosslinks by mass spectrometry (MS), peak assignment using
      theoretical mass lists, and computational reduction of crosslinks to a structure
      by distance geometry methods. To facilitate the unambiguous identification of
      crosslinked peptides from proteolytic digestion mixtures of crosslinked proteins
      by MS, we introduced double 18O isotopic labels into the crosslinking reagent to
      provide the crosslinked peptides with a characteristic isotope pattern. The
      presence of doublets separated by 4 Da in the mass spectra of these materials
      allowed ready discrimination between crosslinked and modified peptides, and
      uncrosslinked peptides using automated intelligent data acquisition (IDA) of
      MS/MS data. This should allow ready automation of the method for application to
      whole expressible proteomes.

PMID- 14592497
TI  - Synthesis and affinity of a possible byproduct of electrophilic radiolabeling of
      [123I]IBZM.
AB  - The iodobenzamide neuroleptic analogue (S)-N-(1-ethylpyrrolidin-2-ylmethyl)-2
      hydroxy-5-iodo-6-methoxybenzamide (5-IBZM) was synthesized stereospecifically and
      its pharmacological properties were compared with the 3-iodo isomer (IBZM) used
      for imaging D(2) receptors in vivo. The isomer 5-IBZM had 100-fold lower affinity
      than IBZM and migrated with similar retention time as the byproduct formed during
      electrophilic iodination of BZM.

PMID- 14592501
TI  - 2,5-disubstituted 3,4-dihydro-2H-benzo[b][1,4]thiazepines as potent and selective
      V2 arginine vasopressin receptor antagonists.
AB  - A number of 2,5-disubstituted benzothiazepines were synthesized and screened for
      their ability to inhibit arginine vasopressin binding to the human V(2) and V(1a)
      receptor subtypes. The more active compounds were subsequently analyzed for their
      antagonist activity in in vitro functional assays. The SAR showed a preference
      for an acidic unit appended from the benzothiazepine scaffold. This substitution
      pattern afforded the most potent and selective analogues in the series. The
      carboxymethyl analogue 4, showed a 140-fold greater selectivity for the V(2) over
      the V(1a) receptor in the binding assay. In the cell-based functional assays this
      analogue was a potent and selective antagonist of the V(2) receptor. The in vitro
      SAR of the series and a description of the in vivo studies around compound 4 is
      described.

PMID- 14592500
TI  - Novel HIV-1 protease inhibitors active against multiple PI-resistant viral
      strains: coadministration with indinavir.
AB  - HIV-1 protease inhibitors (PI) with an N-arylpyrrole moiety in the P(3) position
      afforded excellent antiviral potency and substantially improved aqueous
      solubility over previously reported variants. The rapid in vitro clearance of
      these compounds in human liver microsomes prompted oral coadministration with
      indinavir to hinder their metabolism by the cyctochrome P450 3A4 isozyme and
      allow for in vivo PK assessment.

PMID- 14592502
TI  - 5-amino-1-(2,6-dichloro-4-trifluoromethyl-phenyl)-3-[3H3]-methylsulfanyl-1H
      pyrazole-4-carbonitrile (CTOM): synthesis and characterization of a novel and
      selective insect GABA receptor radioligand.
AB  - Pyrazole 2a is a novel, potent ligand for insect GABA receptors obtained from
      housefly head membrane preparations (K(i)=8 nM). It is 500-fold selective against
      the mammalian receptor (mouse brain preparations). Its specifically tritiated
      version (2b) was synthesized by reduction of disulfide 10 with NaBH(4) followed
      by alkylation with [3H(3)]-CH(3)I.

PMID- 14592503
TI  - Glycosynthase-catalysed syntheses at pH below neutrality.
AB  - The use of the new glycosynthase Ta-beta-GlyE386G and of the already known Ss
      beta-GlyE387G for the synthesis of interesting 4-methylumbelliferyl disaccharides
      and for the galactosylation of alpha- and beta-xylosides of 4-penten-1-ol is
      reported. The results show satisfactory yields of reaction in presence of low
      excesses of acceptors and demonstrated that the high activity of these enzymes at
      pH below neutrality is applicable in the transfer of glucose as well as of
      galactose from the preferred 2-NP-based donors.

PMID- 14592504
TI  - Novel P2X7 receptor antagonists.
AB  - The synthesis and pharmacological evaluation of a new series of potent P2X(7)
      receptor antagonists is disclosed. The compounds inhibit BzATP-mediated pore
      formation in THP-1 cells. The distribution of the P2X(7) receptor in inflammatory
      cells, most notably the macrophage, mast cell and lymphocyte, suggests that
      P2X(7) antagonists have a significant role to play in the treatment of
      inflammatory disease.

PMID- 14592506
TI  - Inhibition of peptide amyloid formation by cationic peptides with homologous
      sequences.
AB  - We have studied the model peptides that undergo self-initiated structural
      transition from alpha-helix to beta-sheet and self-assembling into amyloid
      fibrils. We here constructed an inhibition system of amyloid formation utilizing
      homologous recognition and assembly of peptides with increased solubility. Among
      20 peptides with homologous sequences examined here, cationic peptides showed the
      stronger inhibition ability against the amyloid formation of a model peptide.

PMID- 14592505
TI  - Hit-to-Lead studies: the discovery of potent adamantane amide P2X7 receptor
      antagonists.
AB  - A Hit-to-Lead optimisation programme was carried out on the adamantane high
      throughput screening hit 1 resulting in the discovery of a number of potent
      P2X(7) antagonists.

PMID- 14592507
TI  - Spectrophotometric and ESI-MS/HPLC studies reveal a common mechanism for the
      reaction of various artemisinin analogues with hemin.
AB  - The reaction of hemin with three well known artemisinin analogues, namely
      dihydroartemisinin, artemether and artesunate, was independently analysed by
      visible spectrophotometry and by ESI-MS/HPLC. A very similar reaction pathway
      emerges for all these compounds that matches closely the reaction profile
      previously described for artemisinin. In the course of the reaction
      characteristic isomeric 1:1 drug-hemin adducts are formed as in the case of
      artemisinin; eventual disruption of the porphyrin ring takes place in all cases,
      most likely through oxidative degradation.

PMID- 14592509
TI  - Synthesis and bioactivities of nitronyl nitroxide and RGD containing
      pseudopeptides.
AB  - 1-(1',3'-dioxyl-4',4',5',5'-tetramethyldihydroimidazol-2'-yl)-phenyl-4
      yloxylacetic acid (3), and 1-(1',3'-dioxyl-4',4',5',5'-tetramethyldihydroimidazol
      2'-yl)-phenyl-4-yloxylacetyl-RGDS (13), -RGDV (14), -RGDF (15) were synthesized.
      The ESR measurement gave the same spectroscopy for 3 and 13-15. The NO scavenging
      tests in vitro, anti-platelet aggregation tests in vitro and the anti-thrombosis
      assay in vivo indicated that introducing 3 into the N-terminal of RGDS, RGDV and
      RGDF the corresponding bioactivities for both of 3 and RGD peptides can be
      remained completely. The present combinations provided a beneficial strategy for
      simultaneous scavenging NO and anti-thrombosis, and for the use of spin label of
      RGD peptides in the conformational researches.

PMID- 14592508
TI  - Inhibitors of hepatitis C virus NS3.4A protease 1. Non-charged tetrapeptide
      variants.
AB  - Tetrapeptide-based peptidomimetic compounds have been shown to effectively
      inhibit the hepatitis C virus NS3.4A protease without the need of a charged
      functionality. An aldehyde is used as a prototype reversible electrophilic
      warhead. The SAR of the P1 and P2 inhibitor positions is discussed.

PMID- 14592510
TI  - Design and synthesis of novel RXR-selective modulators with improved
      pharmacological profile.
AB  - New RXR-selective modulators possessing a 6-fluoro trienoic acid moiety (6Z
      olefin) or a fluorinated/heterocyclic-substituted benzene core ring, were
      synthesized in an expedient and selective way. A subset of these compounds was
      evaluated for their metabolic properties (exposure in IRC male mice) and show a
      dramatic increase of exposure compared to our reference compound, 3 (LG101506).

PMID- 14592512
TI  - New anti-malarial peroxides with in vivo potency derived from spongean
      metabolites.
AB  - The structure-activity relationship of the anti-malarial substance 3 having a 6
      carbomethoxymethyl-3-methoxy-1,2-dioxane structure was studied. The ester portion
      of the peroxide 3, showing little in vivo efficacy in malaria-infected mice in
      spite of the potent in vitro activity, was hydrolyzed in serum to afford an
      inactive free acid 4. The amide analogues (8 and 9) robust to mouse serum were
      disclosed to exhibit in vivo anti-malarial potency.

PMID- 14592511
TI  - The design and synthesis of novel orally active inhibitors of AP-1 and NF-kappaB
      mediated transcriptional activation. SAR of in vitro and in vivo studies.
AB  - We have developed novel orally active quinazoline analogues as inhibitors of AP-1
      and NF-kappaB mediated transcriptional activation. Among the derivatives
      prepared, 1-[2-(2-thienyl)quinazolin-4-ylamino]-3-methyl-3-pyrroline-2,5-dione
      (10) showed significant activity in an adjuvant-induced arthritis rat model by
      reducing the swelling by 65% in the non-injected foot. The synthesis, structure
      activity relationship, and in vivo activity are described.

PMID- 14592513
TI  - Structure-activity relationship of benzo[b]thiophene-2-sulfonamide derivatives as
      novel human chymase inhibitors.
AB  - We have identified a new class of chymase inhibitor through a substituent
      analysis of MWP00965, which we previously discovered by in silico screening. TY
      51076 (7) showed high potency (IC(50)=56 nM) and excellent selectivity for
      chymase compared to chymotrypsin and cathepsin G (>400-fold). The synthesis and
      structure-activity relationship of this class are described.

PMID- 14592514
TI  - Utility of boron clusters for drug design. Relation between estrogen receptor
      binding affinity and hydrophobicity of phenols bearing various types of
      carboranyl groups.
AB  - High binding affinity for estrogen receptor and the appearance of estrogenic
      activity require a phenolic ring and an appropriate hydrophobic group adjacent to
      the phenolic ring. A quantitative structure-activity relationship analysis based
      on the values of logP and the pK(a) of the phenolic group showed that the
      hydrophobicity of these compounds is highly correlated to the estrogen receptor
      alpha (ERalpha)-binding affinity. These results should be useful for application
      of these spherical boron clusters (dicarba-closo-dodecaboranes; carboranes) as
      hydrophobic pharmacophores in drug design, as well as for microscopic analysis of
      ER-ligand interactions.

PMID- 14592515
TI  - Interaction of the disodium disuccinate derivative of meso-astaxanthin with human
      serum albumin: from chiral complexation to self-assembly.
AB  - To exploit the promising biochemical activities of naturally-occurring and
      synthetic hydrophobic carotenoids, it is necessary to improve their aqueous
      solubility. The disodium disuccinate derivative of synthetic meso-astaxanthin was
      prepared, and its behavior in pH 7.4 buffer solutions in both the presence and
      absence of fatty acid-free human serum albumin (HSA) was evaluated. The induced
      circular dichroism (CD) spectra and red-shifted absorption band of the optically
      inactive ligand as well as the fluorescence quenching of HSA indicated that at
      low ligand/protein ratios (less than approximately 1:1 ligand/protein), the meso
      carotenoid bound to albumin in monomeric form. Based on the current experimental
      and available structural data for HSA, the binding site was tentatively localized
      to the large interdomain cleft of HSA. Around a 1:1 meso-carotenoid/HSA molar
      ratio, characteristic positive-negative bands appeared in the visible region of
      the CD spectrum, whose amplitudes increased in parallel with the increasing
      concentration of the ligand. These oppositely-signed Cotton effects are typical
      for chiral intermolecular exciton coupling between adjacent polyene chains
      arranged in right-handed assembly. Surprisingly, the magnitude of these induced
      CD bands continued to increase at high ligand/protein ratios (up to 13:1 meso
      carotenoid/HSA). These results suggest the formation of unique, mixed-type
      carotenoid-albumin assemblies in which the HSA molecules themselves serve as
      chiral templates for the generation of supramolecular assemblies.

PMID- 14592516
TI  - Inhibitory effects on mitochondrial complex I of semisynthetic mono
      tetrahydrofuran acetogenin derivatives.
AB  - Modifications in the terminal alpha,beta-unsaturated gamma-methyl-gamma-lactone
      moiety or in the alkyl chain that links this terminal gamma-lactone with the
      alpha,alpha'-dihydroxylated THF system of the natural mono-tetrahydrofuranic
      acetogenins, annonacin and annonacinone, led to the preparation of eight
      semisynthetic derivatives. Their inhibitory effects on mitochondrial complex I is
      discussed and compared with that of the classical complex I inhibitor, rotenone.

PMID- 14592517
TI  - Synthesis and antiproliferative activity of retroetoposide.
AB  - Retro-4'-demethyl-4-epipodophyllotoxin 6 was synthesized in eight steps and 10%
      overall yield from 4'-demethyl-4-epipodophyllotoxin 12. Subsequent coupling of 22
      with 1-O-trimethylsilyl-4,6-O-ethylidene-beta-D-glucoside 26 afforded
      retroetoposide 5 which is 10-fold less cytotoxic than etoposide against L1210
      cell line.

PMID- 14592518
TI  - Biological investigation and structure-activity relationship studies on azadirone
      from Azadirachta indica A. Juss.
AB  - Azadirone 1, a limonoidal constituent of Azadirachta indica is found to possess
      potent cytotoxic activity against a panel of human cancer cell lines in our in
      vitro studies. In vitro screening of a number of semi-synthetic analogues of 1
      revealed that the alpha,beta-unsaturated enone moiety or its equivalent
      conjugated system in A-ring, C-7 acetyloxy/chloroacetyloxy or keto group in B
      ring and the furan moiety are responsible for the activity of 1 and its
      analogues. Compound 1 and two of the semi-synthetic analogues 10 and 13 were
      found to possess good in vivo antitumor activity in modified hollow fiber animal
      models.

PMID- 14592520
TI  - N-arylaminonitriles as bioavailable peptidomimetic inhibitors of cathepsin B.
AB  - To improve the pharmacokinetics of a previously reported series of dipeptidyl
      nitrile cathepsin B inhibitors, the P(2)-P(3) amide group was replaced with an
      arylamine. Further optimization of this template resulted in highly potent and
      selective inhibitors with excellent oral availability.

PMID- 14592521
TI  - A new class of glycogen phosphorylase inhibitors.
AB  - A new class of diacid analogues that binds at the AMP site not only are very
      potent but have approximately 10-fold selectivity in liver versus muscle glycogen
      phosphorylase (GP) in the in vitro assay. The synthesis, structure, and in vitro
      and in vivo biological evaluation of these liver selective glycogen phosphorylase
      inhibitors are discussed.

PMID- 14592523
TI  - Synthesis and biological activity of 2-carbomethoxy-3-catechol-8
      azabicyclo[3.2.1]octanes.
AB  - Cocaine inhibits the dopamine transporter and the consequent elevation of
      dopamine is thought to contribute to the addictive properties of cocaine. Tropane
      analogues of cocaine, targeted to the dopamine transporter (DAT), are a
      significant focus of drug design for cocaine addiction medications. Herein, we
      report the function of the ortho hydroxy substituents in dopamine with respect to
      the azabicyclo[3.2.1]octane skeleton. The introduction of the o-dihydroxyl
      functionality led to reduced binding potency at monoamine transporters, rather
      than enhanced interaction with the DAT. It is therefore likely that the binding
      site for these compounds on the DAT is not the same as that for dopamine.
      Notwithstanding the moderate potency of the free catechols (>100 nM), 7
      manifested stimulant activity with a duration of effect that exceeded 4 h in a
      rat locomotor activity assay. Compound 10, a diacetoxy prodrug for 7, substituted
      fully for cocaine in a rat drug-discrimination paradigm and is now undergoing
      further investigation as a potential medication for cocaine abuse.

PMID- 14592522
TI  - A mechanism for substrate-Induced formation of 6-hydroxyflavin mononucleotide
      catalyzed by C30A trimethylamine dehydrogenase.
AB  - Experiments are described to determine the origin of the 6-hydroxyl group of 6
      hydroxyFMN produced by the substrate-induced transformation of FMN in the C30A
      mutant of trimethylamine dehydrogenase. The conversion of FMN to 6-hydroxyFMN is
      carried out in the presence of H(2)(18)O and 18O(2), and the results clearly show
      that the 6-hydroxyl group is derived from molecular oxygen and not from water.

PMID- 14592519
TI  - Synthesis and in vitro activity of novel isoxazolyl tetrahydropyridinyl
      oxazolidinone antibacterial agents.
AB  - A series of isoxazolyl tetrahydropyridinyl oxazolidinones with various
      substituents at the 3-position of the isoxazole ring have been synthesized and
      their in vitro antibacterial activities (MIC) were evaluated against several Gram
      positive strains including the resistant strains of Staphyloccus and
      Enterococcus, such as MRSA and VRE. One of the most potent compounds synthesized,
      4f, showed comparable or better activity against selected bacterial strains than
      those of linezolid and vancomycin.

PMID- 14592524
TI  - An efficient enzymatic synthesis of thiamin pyrophosphate.
AB  - Thiamin pyrophosphate was synthesized in 71% yield, on a multi-milligram scale,
      using overexpressed thiazole kinase, pyrimidine kinase, thiamin phosphate
      synthase, and thiamin phosphate kinase. This provides a facile route to
      isotopically labeled thiamin pyrophosphate from its readily available pyrimidine
      and thiazole precursors.

PMID- 14592525
TI  - High affinity, bioavailable 3-amino-1,4-benzodiazepine-based gamma-secretase
      inhibitors.
AB  - In this paper, we describe the development of a novel series of high affinity,
      orally bioavailable 3-amino-1,4 benzodiazepine-based gamma-secretase inhibitors
      for the potential treatment of Alzheimer's disease. We disclose structure
      activity relationships based around the 1, 3 and 5 positions of the
      benzodiazepine core structure.

PMID- 14592527
TI  - The osteocyte.
AB  - Osteocytes are the most numerous cells in mature bone and have the potential to
      live as long as the organism itself. However, study and subsequent understanding
      of osteocyte biology has been thwarted by the remote location of the cell in the
      mineralized matrix. This review is intended to synthesize current understanding
      of osteocyte biology and to suggest future paths that will promote understanding
      of this obscure cell and translation of knowledge to disease prophylaxis and
      management.

PMID- 14592528
TI  - The mesothelial cell.
AB  - Mesothelial cells form a monolayer of specialised pavement-like cells that line
      the body's serous cavities and internal organs. The primary function of this
      layer, termed the mesothelium, is to provide a slippery, non-adhesive and
      protective surface. However, mesothelial cells play other pivotal roles involving
      transport of fluid and cells across the serosal cavities, antigen presentation,
      inflammation and tissue repair, coagulation and fibrinolysis and tumour cell
      adhesion. Injury to the mesothelium triggers events leading to the migration of
      mesothelial cells from the edge of the lesion towards the wound centre and
      desquamation of cells into the serosal fluid which attach and incorporate into
      the regenerating mesothelium. If healing is impaired, fibrous serosal adhesions
      form between organs and the body wall which impede vital intrathoracic and
      abdominal movement. Neoplastic transformation of mesothelial cells gives rise to
      malignant mesothelioma, an aggressive tumour predominantly of the pleura.
      Although closely associated with exposure to asbestos, recent studies have
      implicated other factors including simian virus 40 (SV40) in its pathogenesis.

PMID- 14592529
TI  - The pathogenesis of coeliac disease.
AB  - Coeliac disease is a chronic enteropathy caused by intolerance to gluten
      proteins. The true prevalence of this condition is greater than previously
      thought, with increasing numbers of 'silent' cases being diagnosed. Untreated
      coeliac disease is associated with significant morbidity and increased mortality.
      There have been a number of advances in our understanding of the pathogenesis of
      coeliac disease, in particular the mechanisms whereby gluten epitopes are
      processed, become modified by tissue transglutaminase (tTG) and then interact
      with HLA restricted T cells. An improved understanding of the immune response to
      gluten is likely to lead to the development of novel strategies for the treatment
      of coeliac disease.

PMID- 14592530
TI  - Atherothrombosis: the role of tissue factor.
AB  - Atherothrombosis, defined as atherosclerotic lesion disruption with superimposed
      thrombus formation, is the major cause of acute coronary syndromes and
      cardiovascular deaths. It is the leading cause of morbidity and mortality in the
      industrialized world. Plaque composition, rather than luminal stenosis, is
      recognized as the major determinant of this disease. Since tissue factor is found
      within atheroma and also in the bloodstream of atherosclerotic patients, it
      likely plays a key role in determining both plaque and blood thrombogenicity.
      Ongoing clinical and preclinical studies are evaluating the therapeutic
      possibilities of specific inhibition of the tissue factor pathway. Here, we will
      review the role of tissue factor in atherothrombosis.

PMID- 14592531
TI  - Tensin.
AB  - Tensin is a cytoplasmic phosphoprotein that localized to integrin-mediated focal
      adhesions. It binds to actin filaments and contains a phosphotyrosine-binding
      (PTB) domain, which interacts with the cytoplasmic tails of beta integrin. These
      interactions allow tensin to link actin filaments to integrin receptors. In
      addition, tensin has an Src Homology 2 (SH2) domain capable of interacting with
      tyrosine-phosphorylated proteins. Furthermore, several factors induce tyrosine
      phosphorylation of tensin. Thus, tensin functions as a platform for dis/assembly
      of signaling complexes at focal adhesions by recruiting tyrosine-phosphorylated
      signaling molecules through the SH2 domain, and also by providing interaction
      sites for other SH2-containing proteins. Analysis of knockout mice has
      demonstrated critical roles of tensin in renal function, muscle regeneration, and
      cell migration. Therefore, tensin and its downstream signaling molecules may be
      targets for therapeutic interventions in renal disease, wound healing and cancer.

PMID- 14592532
TI  - The chemokine receptor, CCR5.
AB  - The chemokine receptor, CCR5, is a G protein coupled receptor responsible for
      some of the effects of the chemokines CCL3, CCL4 and CCL5. It is also one of the
      co-receptors for the entry of human immunodeficiency virus-1 (HIV-1) into cells.
      Regulation of CCR5 number on cells is, therefore, important for determining the
      infection rate by HIV-1.

PMID- 14592533
TI  - The role of scavenger receptor class B type I (SR-BI) in lipid trafficking.
      defining the rules for lipid traders.
AB  - The scavenger receptor class B type I (SR-BI) is a 509-amino acid, 82 kDa
      glycoprotein, with two cytoplasmic C- and N-terminal domains separated by a large
      extracellular domain. The aim of this review is to define the role of SR-BI as a
      lipoprotein receptor responsible for selective uptake of cholesteryl esters (CE)
      from high density lipoprotein (HDL) and low density lipoprotein (LDL) and free
      cholesterol (FC) efflux to lipoprotein acceptors. These activities depend on
      lipoprotein binding to its extracellular domain and subsequent lipid exchange at
      the plasma membrane. CE selective uptake supplies cholesterol to liver and
      steroidogenic tissues, for biliary cholesterol secretion and steroid hormone
      synthesis. Genetically modified mice have confirmed SR-BI's major role in tissue
      cholesterol uptake and in reverse cholesterol transport, i.e. cholesterol
      turnover. Accordingly, cellular cholesterol level, estrogens and trophic hormones
      regulate SR-BI expression by both transcriptional and post-transcriptional
      mechanisms. Importantly, mouse SR-BI overexpression has both corrective and
      preventive effects on atherosclerosis. Human SR-BI has very similar tissue
      distribution, binding properties and lipid transfer activities compared to rodent
      SR-BI. However, human plasma has most of its cholesterol in LDL. Thus, there is
      considerable interest to develop anti-atherogenic strategies involving human SR
      BI-mediated increases in reverse cholesterol transport through HDL and/or LDL.

PMID- 14592534
TI  - Quantitation of mRNA levels of steroid 5alpha-reductase isozymes: a novel method
      that combines quantitative RT-PCR and capillary electrophoresis.
AB  - A novel, accurate, rapid and modestly labor-intensive method has been developed
      to quantitate specific mRNA species by reverse transcription-polymerase chain
      reaction (RT-PCR). This strategy combines the high degree of specificity of
      competitive PCR with the sensitivity of laser-induced fluorescence capillary
      electrophoresis (LIF-CE). The specific target mRNA and a mimic DNA fragment, used
      as an internal standard (IS), were co-amplified in a single reaction in which the
      same primers are used. The amount of mRNA was then quantitated by extrapolation
      from the standard curve generated with the internal standard. PCR primers were
      designed to amplify both a 185 bp fragment of the target cDNA for steroid 5alpha
      reductase 1 (5alpha-R1) and a 192 bp fragment of the target cDNA for steroid
      5alpha-reductase type 2 (5alpha-R2). The 5' forward primers were end-labeled with
      6-carboxy-fluorescein (6-FAM). Two synthetic internal standard DNAs of 300 bp
      were synthesized from the sequence of plasmid pEGFP-C1. The ratio of fluorescence
      intensity between amplified products of the target cDNA (185 or 192 bp fragments)
      and the competitive DNA (300 bp fragment) was determined quantitatively after
      separation by capillary electrophoresis and fluorescence analysis. The accurate
      quantitation of low-abundance mRNAs by the present method allows low-level gene
      expression to be characterized.

PMID- 14592535
TI  - Oxidative damage and altered antioxidant enzyme activities in the small intestine
      of streptozotocin-induced diabetic rats.
AB  - The small intestine exhibits numerous morphological and functional alterations
      during diabetes. Oxidative stress, a factor implicated in the pathogenesis of
      diabetic complications may contribute towards some of these alterations. We
      therefore investigated the occurrence of oxidative stress in the small intestine
      during diabetes by measuring the extent of oxidative damage as well as the status
      of the antioxidant defense system. Significant increases in lipid peroxidation
      (four-fold) as measured by TBARS and protein oxidation (38%) as measured by
      protein carbonyl content were observed after 6 weeks of diabetes. A distinct
      elevation in the activities of catalase (123.9%) and superoxide dismutase (71.9%)
      and a decline in the activity of glutathione peroxidase (67.7%) were also
      observed. The steady state mRNA levels of these enzymes measured by RT-PCR were,
      however, unchanged suggesting the absence of transcriptional control. In
      contrast, no changes in the levels of protein and non-protein thiols as well as
      the activities of glutathione reductase and glutathione-S-transferase were
      detected. Interestingly, decreases in the activities of xanthine oxidase (XO;
      25.7%) and xanthine dehydrogenase (XDH; 42.6%) indicate that they do not
      contribute significantly to oxidative damage. The results thus reveal the
      occurrence of oxidative stress in the small intestine during diabetes and suggest
      its possible involvement in some of the accompanying functional alterations.

PMID- 14592536
TI  - Distinct role and functional mode of TR3 and RARalpha in mediating ATRA-induced
      signalling pathway in breast and gastric cancer cells.
AB  - All-trans retinoic acid (ATRA) affects cell proliferation, differentiation and
      apoptosis through its receptors, RARs and RXRs. Besides these, other receptors
      such as orphan receptor TR3, are also involved in the regulatory process of ATRA.
      However, how different receptors function in response to ATRA is still largely
      unknown. In the present study, we found that formation of TR3/RXRalpha
      heterodimers in the nucleus and their subsequent translocation into the
      cytoplasm, in association with regulation of apoptosis-related proteins Bcl-2,
      Bcl-xl and Bax, was critical for apoptosis induction by ATRA in breast cancer
      cells MCF-7. When such translocation was blocked by Leptomycin B (LMB), ATRA
      induced apoptosis was consequently abolished. However, in ATRA-induced gastric
      cancer cells MGC80-3, RXRalpha heterodimerised with RARalpha but not with TR3,
      and remained in the nucleus exerting its effect on cell cycle regulation. When
      transfected with antisense-RARalpha, MGC80-3 cells changed from ATRA-sensitive to
      ATRA-resistant and most cells were arrested in the S phase, implying the
      importance of RARalpha in cell cycle regulation. Furthermore, we demonstrated
      that the effects of ATRA depend on the relative levels of TR3, RARalpha and
      RXRalpha expression in cancer cells. In ATRA-induced MCF-7 cells, highly
      expressed TR3 favours the formation of TR3/RXRalpha and promotes the TR3/RXRalpha
      signalling pathway causing apoptosis; while in ATRA-induced MGC80-3 cells, high
      expression of RARalpha favours the formation of RARalpha/RXRalpha and promotes
      the RXRalpha/RARalpha signalling pathway in mediating cell cycle regulation. In
      conclusion, these results reveal the novel mechanism that cellular expression and
      location of protein is associated with diverse signalling transduction pathways
      and the resultant physiological process.

PMID- 14592537
TI  - Stimulation of in vitro angiogenesis by nitric oxide through the induction of
      transcription factor ETS-1.
AB  - The aim of this study was to examine whether transcription factor ETS-1, which is
      responsible for the expression of metalloproteinases and integrin beta(3), is
      implicated in the induction of nitric oxide (NO)-induced angiogenesis. Bovine
      aortic endothelial cells were cultured on type I collagen gel to measure the
      length of the formed tube-like structure, which is a marker for in vitro
      angiogenesis. The addition of S-nitroso-N-acetylpenicillamine (SNAP), an NO
      donor, to confluent endothelial cells stimulated the formation of the tube-like
      structure, with disappearance of covered endothelial cell monolayers. Another NO
      donor 2,2'-(hydroxynitrosohydrazono)bis-ethanamine (NOC 18) also induced the
      formation of the tube-like structure. In contrast to the induction of the
      formation of the tube-like structure by SNAP, it reduced cell proliferation. SNAP
      and NOC 18 also increased the expression of the ets-1 mRNA level in a
      concentration-dependent manner. The maximum expression was observed at 2h after
      their addition. Moreover, the SNAP-induced in vitro angiogenesis, ets-1 mRNA
      expression and ETS-1 protein expression were strongly reduced by the treatment
      with ets-1 antisense oligonucleotide. These results strongly suggest that NO
      stimulates in vitro angiogenesis through the induction of ETS-1 expression. NO
      appears to stimulate endothelial cell differentiation to the angiogenic phenotype
      via the induction of ETS-1 transcription factor.

PMID- 14592538
TI  - Cisplatin-resistance modulates the effect of protein synthesis inhibitors on
      spermidine/spermine N(1)-acetyltransferase expression.
AB  - Cisplatin (DDP)-resistance confers a deficient expression of spermidine/spermine
      N(1)-acetyltransferase (SSAT) gene in response to the spermine analog N(1),N(12)
      bis(ethyl)spermine (BESpm) in the DDP-resistant human ovarian carcinoma cell line
      (C13*), compared with their parental DDP-sensitive 2008 cells. This SSAT gene
      deficiency is correlated with a reduced growth sensitivity to spermine analogs.
      This study was performed to determine whether SSAT gene expression of resistant
      cells was kept suppressed by labile repressor proteins developed during
      resistance selection. We show here that inhibitory concentrations of
      cycloheximide (CHX) and anisomycin (ANISO) differentially affect BESpm-induced
      SSAT activity in 2008 and in C13* cells in a concentration-dependent manner and
      allow resistant cells to reach activation levels comparable to those of the
      sensitive cells. Northern blot analysis revealed that both CHX and ANISO in
      combination with BESpm caused a synergistic BESpm-mediated accumulation of SSAT
      mRNA in C13* cells, with respect to each drug alone, while in 2008 cells only a
      slight increase was observed. The more pronounced effect of inhibitors on the
      SSAT activity induced by BESpm in the resistant cells was also the result of a
      more prolonged stabilization of SSAT mRNA and enzyme protein. By contrast, sub
      inhibitory concentrations of CHX and ANISO did not significantly stimulate BESpm
      induced SSAT transcription and activity. These results suggest that labile
      repressor proteins, related to DDP-resistance phenotype, play a regulatory role
      in SSAT gene expression, and further indicate that by overcoming this inhibitory
      control it is possible to recover BESpm response.

PMID- 14592539
TI  - Purification of a specific inhibitor of pyroglutamyl aminopeptidase II from the
      marine annelide Hermodice carunculata. in vivo effects in rodent brain.
AB  - An inhibitor of the metallo-ectoenzyme, pyroglutamyl aminopeptidase II (PPII), a
      thyrotropin releasing hormone-specific peptidase, was identified by screening
      extracts from marine species of the Cuban coast-line belonging to the phylla
      Chordata, Echinodermata, Annelida, Mollusca, Cnidaria, Porifera, Chlorophyta and
      Magnoliophyta. Isolation of the inhibitor (HcPI), from the marine annelide
      Hermodice carunculata, was achieved by trichloroacetic acid treatment of the
      aqueous extract, followed by ion-exchange chromatography on DEAE Sephacel, gel
      filtration on Sephadex G-25 and reverse phase-HPLC. HcPI had a small apparent
      molecular weight (below 1000 Da) and was not a peptide. It inhibited rat PPII (a
      membrane preparation with 8.5mg protein/ml) with an apparent K(i) of 51 nM. HcPI
      did not inhibit serine (trypsin, chymotrypsin, elastase and dipeptidyl
      aminopeptidase IV), cysteine (papain, bromelain and pyroglutamyl aminopeptidase
      I), aspartic (pepsin and recombinant human immunodeficiency virus 1 protease
      (HIV1-PR)) nor other metallo proteinases (collagenase, gelatinase, angiotensin
      converting enzyme, aminopeptidase N and carboxypeptidase A). HcPI was non-toxic
      and active in vivo. Intraperitoneal injection of HcPI reduced mouse pituitary and
      brain PPII activity. Potency of the effect was higher in hypophysis and
      hypothalamus than in other brain regions. Intrathecal administration to male rats
      reduced PPII activity in the spinal cord. In conclusion we have identified a
      specific inhibitor of PPII that is the first M1 family zinc metallo-peptidase
      inhibitor isolated from marine invertebrates. It may be useful for elucidating
      the in vivo role of PPII in the pituitary and central nervous system.

PMID- 14592540
TI  - Hexadecylphosphocholine inhibits phosphatidylcholine synthesis via both the
      methylation of phosphatidylethanolamine and CDP-choline pathways in HepG2 cells.
AB  - We reported in a recent publication that hexadecylphosphocholine (HePC), a
      lysophospholipid analogue, reduces cell proliferation in HepG2 cells and at the
      same time inhibits the biosynthesis of phosphatidylcholine (PC) via CDP-choline
      by acting upon CTP:phosphocholine cytidylyltransferase (CT). We describe here the
      results of our study into the influence of HePC on other biosynthetic pathways of
      glycerolipids. HePC clearly decreased the incorporation of the exogenous
      precursor [1,2,3-3H]glycerol into PC and phosphatidylserine (PS) whilst
      increasing that of the neutral lipids diacylglycerol (DAG) and triacylglycerol
      (TAG). Interestingly, the uptake of L-[3-3H]serine into PS and other
      phospholipids remained unchanged by HePC and neither was the activity of either
      PS synthase or PS decarboxylase altered, demonstrating that the biosynthesis of
      PS is unaffected by HePC. We also analyzed the water-soluble intermediates and
      final product of the CDP-ethanolamine pathway and found that HePC caused an
      increase in the incorporation of [1,2-14C]ethanolamine into CDP-ethanolamine and
      phosphatidylethanolamine (PE) and a decrease in ethanolamine phosphate, which
      might be interpreted in terms of a stimulation of CTP:phosphoethanolamine
      cytidylyltransferase activity. Since PE can be methylated to give PC, we studied
      this process further and observed that HePC decreased the synthesis of PC from PE
      by inhibiting the PE N-methyltransferase activity. These results constitute the
      first experimental evidence that the inhibition of the synthesis of PC via CDP
      choline by HePC is not counterbalanced by any increase in its formation via
      methylation. On the contrary, in the presence of HePC both pathways seem to
      contribute jointly to a decrease in the overall synthesis of PC in HepG2 cells.

PMID- 14592541
TI  - In situ evidence of an alternative oxidase and an uncoupling protein in the
      respiratory chain of Aspergillus fumigatus.
AB  - Aspergillus fumigatus is an unusual pathogen in immunocompetent individuals; its
      incidence has increased in the last decades in patients immunocompromised, like
      those with chronic granulomatosis disease and AIDS. The aim of this study was to
      identify differences between the respiratory chain of host and the fungus
      planning to use the later as a pharmacological target. We evaluated respiration,
      membrane potential and oxidative phosphorylation of mitochondria of the
      spheroplasts of A. fumigatus in situ, after permeabilization with digitonin.
      Firstly, a functional respiratory chain (complex I-V) was demonstrated: adenosine
      5'-diphosphate (ADP) induced an oligomycin-sensitive transition from resting to
      phophorylating respiration in the presence of the oxidizable substrates malate,
      glutamate, alpha-ketoglutarate, pyruvate, dihydroorotate, succinate, N,N,N',N'
      tetramethyl-p-phenylenediamine (TMPD) and exogenous NADH. In addition, the
      ability of the fungus to oxidize exogenous NADH, as well as the insensitivity of
      its respiration to rotenone, in association with the sensitivity to flavone,
      indicate the presence of an alternative NADH-ubiquinone oxidoreductase; the
      partial sensitivity of respiration to antimycin A and cyanide, in association
      with the sensitivity to benzohydroxamic acid, indicates the presence of an
      alternative oxidase. The fatty acid-uncoupled respiration was partly reversed by
      bovine serum albumin (BSA) and guanosine 5'-triphosphate (GTP) and was
      insensitive to either carboxyatractyloside or ADP. These results, together with
      evidences obtained using antibodies raised against uncoupling protein (UCP) from
      potato, indicate in addition, the presence of an uncoupling protein in the
      respiratory chain of A. fumigatus.

PMID- 14592542
TI  - Special issue in honour of Sir John Vane, F.R.S., Nobel Laureate, the discoverer
      of the mechanism of action of aspirin. Proceedings of the Jagiellonian Medical
      Research Center Club Meeting, Krakow, Poland, 31 May-3 June 2003.

PMID- 14592543
TI  - The mechanism of action of aspirin.
AB  - The therapy of rheumatism began thousands of years ago with the use of decoctions
      or extracts of herbs or plants such as willow bark or leaves, most of which
      turned out to contain salicylates. Following the advent of synthetic salicylate,
      Felix Hoffman, working at the Bayer company in Germany, made the acetylated form
      of salicylic acid in 1897. This drug was named "Aspirin" and became the most
      widely used medicine of all time. In 1971, Vane discovered the mechanism by which
      aspirin exerts its anti-inflammatory, analgesic and antipyretic actions. He
      proved that aspirin and other non-steroid anti-inflammatory drugs (NSAIDs)
      inhibit the activity of the enzyme now called cyclooxygenase (COX) which leads to
      the formation of prostaglandins (PGs) that cause inflammation, swelling, pain and
      fever. However, by inhibiting this key enzyme in PG synthesis, the aspirin-like
      drugs also prevented the production of physiologically important PGs which
      protect the stomach mucosa from damage by hydrochloric acid, maintain kidney
      function and aggregate platelets when required. This conclusion provided a
      unifying explanation for the therapeutic actions and shared side effects of the
      aspirin-like drugs. Twenty years later, with the discovery of a second COX gene,
      it became clear that there are two isoforms of the COX enzyme. The constitutive
      isoform, COX-1, supports the beneficial homeostatic functions, whereas the
      inducible isoform, COX-2, becomes upregulated by inflammatory mediators and its
      products cause many of the symptoms of inflammatory diseases such as rheumatoid
      and osteoarthritis.

PMID- 14592544
TI  - Studies on the mechanism of action of anti-inflammatory drugs. A paper in honour
      of John Vane.

PMID- 14592545
TI  - Variants of cyclooxygenase-1 and their roles in medicine.
AB  - Acetaminophen (paracetamol) and other analgesic/antipyretic drugs such as
      dipyrone have been postulated to act centrally through inhibition of
      cyclooxygenases (COXs). COX activity in lipopolysaccharide-stimulated mammalian
      leukocytes, microglial cells, and platelets is inhibited by these drugs at
      physiological concentrations. Yet purified COX enzymes are poorly inhibited by
      acetaminophen, particularly under conditions of high oxidant tone and elevated
      substrate levels. This suggests the presence of cell-specific differences that
      govern COX inhibition by these drugs. COX-3, a variant of COX-1, has been found
      in canine brain and is inhibited by acetaminophen and dipyrone at physiological
      concentrations. Additionally, other new COX-1-derived proteins called PCOX have
      been identified that do not make prostaglandins but apparently bind heme and may
      have other enzymatic properties. Antibodies specific for these variants detect
      analogous proteins in human tissues. Expression of COX variants is postulated to
      be an integral part of the mechanism of action of analgesic/antipyretic drugs.

PMID- 14592546
TI  - COX-1 and COX-3 inhibitors.
AB  - Low doses of aspirin reduce both pain and fever, whereas the anti-inflammatory
      action of aspirin requires a much higher dose. It is possible that inhibition of
      cyclooxygenase (COX)-1 is the major action of aspirin involved in its analgesic
      and antipyretic effects, and inhibition of COX-2 is responsible for its anti
      inflammatory action. We compared the analgesic effects of an aspirin-like drug
      (diclofenac) and a centrally acting analgesic (paracetamol) in the mouse
      stretching test and confirmed that the analgesic action of the aspirin-like drug
      was peripheral. Two possible sites have been postulated for the antipyretic
      action of non-steroid anti-inflammatory drugs; (a) inhibition of COX in
      endothelial cells of hypothalamic blood vessels or (b) inhibition of COX
      synthesising prostaglandins near sensory receptors of sub-diaphragmatic vagal
      afferents. The antipyretic action of aspirin may be mediated by inhibition of COX
      3 in hypothalamic endothelial cells or by inhibition of COX-1 localised close to
      sensory receptors of peripheral vagal afferents. It is also possible that both
      enzymes are involved in the antipyretic action of aspirin. Whereas
      lipopolysaccharide (LPS)-induced fever is attenuated in COX-2 gene-deleted mice,
      suggesting that COX-2 is responsible for this type of fever, the COX-1 gene may
      also be important in temperature regulation and in mediating the pyresis that
      occurs in the absence of infection.

PMID- 14592548
TI  - TNFalpha regulates renal COX-2 in the rat thick ascending limb (TAL).
AB  - We have examined cyclooxygenase (COX)-2-dependent mechanisms in preglomerular
      microvessels and the thick ascending limb (TAL). These renal structures are
      linchpins in the regulation of the renal circulation and extracellular fluid
      volume. Cytochrome P450 monooxygenases are the principal oxygenases in the TAL
      segment; however, COX-2 can be expressed in the TAL, as when challenged by
      angiotensin II. Glucocorticoids also affect the expression and activity of
      oxygenases in the TAL. Before adrenalectomy, <2% TAL cells expressed COX-2;
      after, >30% of TAL cells expressed COX-2. Recruitment of COX-2 is initiated in
      the renal cortex and proceeds to the medulla associated with: (1) COX-2 mRNA
      accumulation; (2) increased COX-2 expression; and (3) a two-fold increase in PGE2
      production by cortical microsomes. These changes were nullified by dexamethasone.
      COX-2 mRNA, protein expression and PGE2 synthesis in the TAL are also increased
      in response to increased extracellular Ca2+. The Ca2+ sensing receptor is G
      protein coupled and responds to changes in extracellular Ca2+ concentration by
      increasing protein kinase C activity to produce expression of COX-2. Thus,
      multiple signaling pathways contribute to COX-2 expression in TAL cells.

PMID- 14592547
TI  - Control of COX-2 and iNOS gene expressions by aspirin and salicylate.

PMID- 14592549
TI  - Aspirin insensitive eicosanoid biosynthesis in cardiovascular disease.
AB  - Inhibition of platelet cyclooxygenase (COX)-1 is involved in aspirin
      cardioprotection observed in clinical trials, but, in some patients, aspirin is
      unable to protect from thrombotic complications. An incomplete suppression of
      platelet thromboxane (TX) A2 biosynthesis has been assumed to participate in the
      phenomenon of aspirin resistance, as a consequence of the following possible
      mechanisms: (i) COX-2 expression in newly formed platelets; (ii) pharmacodynamic
      interactions between aspirin and coadministered nonsteroidal antiinflammatory
      drugs (e.g. ibuprofen); (iii) expression of variant isoforms of COX-1 with
      reduced sensitivity to irreversible inactivation at Ser529. Furthermore, aspirin
      failure may be due to enhanced formation of vasoactive and/or proaggregatory
      eicosanoids despite an almost complete suppression of platelet TXA2 biosynthesis
      by aspirin. Thus, in a subset of patients with unstable angina treated with low
      dose aspirin, to almost completely block platelet COX-1 activity, enhanced TXA2
      biosynthesis in vivo has been demonstrated, presumably through an increased
      generation of COX-2-dependent PGH2 in plaque monocytes/macrophages or activated
      vascular cells. The concomitant increased formation of 8-iso-PGF2alpha, one of
      the most abundant F2-isoprostanes in humans, generated by free-radical catalyzed
      arachidonate peroxidation, may be involved in aspirin resistance because of its
      capacity to induce platelet and vascular smooth muscle cell activation through
      the interaction with thromboxane receptors (TPs). Finally, enhanced production of
      vasoactive cysteinyl leukotrienes (cys-LTs) occurs in unstable angina despite
      conventional antithrombotic and antianginal treatment. The use of selective
      pharmacological tools (i.e. highly selective COX-2 inhibitors, TP antagonists,
      cys-LT inhibitors and antagonists) will allow to ascertain the contribution of
      aspirin insensitive eicosanoid biosynthesis in aspirin cardioprotective failure.

PMID- 14592550
TI  - Obligatory role of lipid mediators in platelet-neutrophil adhesion.
AB  - Platelet-neutrophil interactions play an important role in thrombotic and
      inflammatory responses. Although it is well known that adhesion of platelets to
      neutrophils requires interactions of adhesion molecules on platelets such as P
      selectin, or GPIIb/IIIa with their counterparts on neutrophils, little is known
      on the role of lipid mediators in this response. Here we studied involvement of
      thromboxane (TX) A2, platelet activating factor (PAF) and cysteinyl leukotrienes
      (cysLTs) in the mechanisms of platelet-neutrophil adhesion that was induced by
      thrombin (10-100 mU/ml), fMLP (0.01-1 microM) or LPS (0.001-100 microg/ml). All
      three stimulators in a concentration- and time-dependent manner induced platelet
      neutrophil adhesion as quantified by the method of Jungi et al. [Blood 67(3)
      (1986) 629]. Platelet-neutrophil adhesion induced by each of the three activators
      was inhibited by blocking antibodies towards P-selectin, GPIIb/IIIa or CD18, but
      it was not affected by anti-E selectin antibody. Moreover, platelet-neutrophil
      adhesion induced by thrombin, fMPL or LPS was inhibited by the inhibitor of
      cyclooxygenase (aspirin), by TXA2 synthase inhibitor (camonagrel), by PAF
      receptor antagonist (WEB 2170), by the inhibitor of FLAP (MK 886) and by cysLTs
      receptors antagonist (MK 571). On the other hand, the selective inhibitor of COX
      2 (rofecoxib) as well as the inhibitor of cytochrome P450-dependent monoxygenase
      (17-ODYA) were ineffective. In summary, adhesion of platelets to neutrophils is
      regulated not only by specific interaction between adhesion molecules on
      platelets and neutrophils, but also by lipid mediators such as TXA2, PAF and
      cysLTs released upon activation of platelets or/and neutrophils.

PMID- 14592551
TI  - COX-2 lack of function in hypoxia-induced ocular surface inflammation.
AB  - Injury to the ocular surface increases corneal epithelial production of
      cyclooxygenase (COX)-derived eicosanoids but this increase correlates poorly to
      the inflammatory sequelae. Moreover, corticosteroids are effective in treatment
      of this inflammation but NSAIDs are not. The discovery of COX-2 that is
      differentially affected by common NSAIDs reopened the question of the role of
      prostaglandins in ocular surface inflammation. We examined the presence and
      inducibility of COX-2 in the corneal epithelium following hypoxia-induced injury
      in vivo and in vitro. COX-2, but not COX-1, protein levels markedly increased
      following hypoxia. Use of the selective COX-2 inhibitor, NS-398, indicated that
      COX activity in hypoxic corneas or cells is essentially that of COX-2; in control
      cells, both COX-1 and COX-2 contributed equally to the production of PGE2. COX-2
      protein overexpression induced by hypoxia was not associated with a parallel
      increase in PGE2 accumulation but the enzyme regained full catalytic activity
      when cells were re-exposed to normoxia in the presence of heme and arachidonic
      acid. Decreases in the levels of oxygen and heme, essential substrates/cofactors
      for COX catalytic activity, contributed to a diminished prostanoid production
      during hypoxia. These results suggest that in hypoxic injury, molecules other
      than COX-derived prostanoids play a major pro-inflammatory role. Furthermore,
      this study provides an explanation for the ineffectiveness of classical NSAIDs in
      the treatment of hypoxia-related ocular surface inflammation.

PMID- 14592552
TI  - Effects of phenacetin and its metabolite p-phenetidine on COX-1 and COX-2
      activities and expression in vitro.
AB  - The present study was aimed to test the possible cyclooxygenase (COX)-1/COX-2
      selectivity of the old analgesic drug phenacetin and its metabolite p
      phenetidine, which exhibits high renal toxicity. Paracetamol (acetaminophen), the
      main metabolite of phenacetin with low renal toxicity, and indomethacin were
      selected as reference compounds. Collagen-stimulated platelet thromboxane B2
      (TxB2) production and phorbol 12-myristate-13-acetate (PMA)-induced neutrophil
      prostaglandin E2 (PGE2) synthesis were used as indicators for COX-1 and COX-2
      activity, respectively. Phenacetin was even less potent than paracetamol to
      reduce the production of both TxB2 and PGE2, and no clear preference for either
      of the COX-enzymes was seen. P-phenetidine was a more potent inhibitor, already
      at nanomolar level, of the synthesis of these prostanoids than indomethacin and
      showed some preference to COX-2 inhibition. Somewhat higher, micromolar,
      concentrations of p-phenetidine also reduced COX-2 expression in neutrophils. We
      suggest that the very potent inhibitory activity of p-phenetidine on PGE2
      synthesis combined with the reduction of COX-2 expression could explain the renal
      papillary necrosis in phenacetin kidney.

PMID- 14592554
TI  - Activation of nuclear receptors by prostaglandins.
AB  - Deletion of membrane receptors for prostaglandins has revealed their importance
      in diverse biological systems. Some evidence has accrued to support the
      contention that they may also ligate nuclear receptors, particularly peroxisomal
      proliferator activator receptors (PPARs). This is most pronounced in the case of
      15-deoxy PGJ2, a cyclopentanone derivative of PGJ2 as a ligand for PPARgamma.
      However, while this compound can ligate the PPAR, the quantities formed in vivo
      suggest that this is an unlikely endogenous ligand. Furthermore, biosynthesis is
      unaltered in murine atherosclerosis and other inflammatory and metabolic
      disorders where activation of this PPAR has been implicated. The suggestion that
      prostaglandins serve as endogenous ligands for nuclear receptors is presently
      configured on the use of synthetic compounds and immunoreactive quantitation of
      dubious validity. The application of quantitatively precise and sensitive
      physicochemical methodology will enhance experiments designed to address this
      hypothesis.

PMID- 14592553
TI  - Heme oxygenase attenuated angiotensin II-mediated increase in cyclooxygenase
      activity and decreased isoprostane F2alpha in endothelial cells.
AB  - Heme oxygenase (HO) regulates cellular heme levels and catalyzes the formation of
      bilirubin and carbon monoxide (CO). We hypothesized that the status of the
      endothelial HO system influences the angiotensin (Ang) II-induced increase in the
      endothelial cell (EC) production of PGE2, eicosanoids which modulate the vascular
      actions of Ang II. In this study, we investigated the effect of interventions
      that suppress HO activity or induce HO-1 gene expression on Ang II-mediated
      increase in PGE2 in cultures of human microvessel endothelial cells (EC).
      Incubation of EC with Ang II (100 ng/ml) for 24 h increased the levels of PGE2 in
      the culture media. This effect of Ang II on prostaglandin production by EC was
      attenuated in cells treated with heme, but was magnified in cells treated with
      the HO inhibitor, Stannis mesoporphyrin (SnMP). Upregulation of HO-1 gene
      expression by retrovirus-mediated delivery of the human HO-1 gene attenuated heme
      and Ang II-induced prostaglandin synthesis. We also investigated the
      physiological significance of human HO-1 overexpression on attenuation of Ang II
      mediated oxidative stress. Decreases in COMET levels were found in EC transduced
      with the HO-1 gene. These results indicate that overexpression of the HO system
      in EC exerts an inhibitory influence on Ang II-induced synthesis of
      prostaglandins and attenuates DNA damage caused by exposure to Ang II.

PMID- 14592555
TI  - Effect of aspirin on constitutive nitric oxide synthase and the biovailability of
      NO.
AB  - INTRODUCTION: Aspirin decreases the activity of iNOS and the formation of
      prostanoids. Constitutive nitric oxide synthase (cNOS) is present in endothelial
      cells, platelets, leukocytes and neurons, yet no data are available on the effect
      of aspirin on cNOS and the bioavailability of NO produced by this enzyme.
      MATERIALS AND METHODS: Human umbilical vein endothelial cells (HUVECs), rat
      adrenal gland pheochromocytoma cells (PC-12) and human platelets were incubated
      with different aspirin concentrations. The kinetics of NO, O2- and ONOO- release
      were measured simultaneously in single cells or platelet suspensions using tandem
      electrochemical nanosensors. The NO, O2- and ONOO- release from cells and
      platelets was stimulated with calcium ionophore and collagen, respectively. cNOS
      expression was estimated by Western blot analysis. RESULTS: Incubation of HUVECs
      and PC-12 with 10(-5) mol/l of aspirin increased cNOS expression by 70 +/- 7% and
      50 +/- 5, respectively. However, the NO concentration increased only by 33% in
      HUVECs incubated with the same aspirin concentration. Incubation of HUVECs with
      aspirin also increased the O2- and ONOO- production. Therefore the
      bioavailability of NO increased only slightly in endothelium and did not reflect
      the increase in eNOS. This was in contrast to platelets, where maximal NO
      bioavailability almost doubled after incubation with aspirin. CONCLUSIONS:
      Aspirin did not have a significant effect on the NO bioavailability in
      endothelial cells. However, aspirin highly improved the NO production in
      platelets. The high NO production in platelets may counteract the effect of
      thromboxane, inhibit platelet aggregation, and compensate for the reduction of
      prostacycline concentration by aspirin.

PMID- 14592556
TI  - Mechanisms of angiotensin-converting enzyme inhibitor induced thrombolysis in
      Wistar rats.
AB  - Our in vivo assay for thrombolysis consisted of recording the weight of platelet
      rich thrombi adhering to a collagen strip that was superfused with arterial blood
      in extracorporal circulation of anaesthetised Wistar rats. Immediate thrombolysis
      occurred in response to intravenously administrated angiotensin-converting enzyme
      inhibitor (ACE-I) at non-hypotensive doses of 3-30 microg kg(-1)
      (captopril<perindopril<quinapril). The thrombolytic response lasted up to 3 h
      with maximum reduction of the weight of thrombus by 75%. Pretreatment with COX-1
      and COX-3 inhibitors (aspirin at a low dose of 1 mg kg(-1), SC 560 and
      acetaminophen, 0.3-3 mg kg(-1)) slightly augmented thrombolysis by ACE-I, while
      COX-2 inhibitors (nimesulide and coxibs at doses <1 mg kg(-1) and aspirin at a
      high dose of 50 mg kg(-1)) or a kinin B2 receptor antagonist (icatibant)
      abolished it. NOS inhibition by L-NAME blunted and delayed thrombolysis by ACE-I.
      In parallel to maximum thrombolysis by quinapril (30 microg kg(-1)), plasma
      levels of 6-keto-PGF1alpha rose significantly from 40 +/- 7 to 554 +/- 91 pg ml(
      1) (n=5, mean +/- S.D.), while basal levels of PGE2 (12 +/- 3 pg ml(-1)) and TXB2
      (47 +/- 11 pg ml(-1)) remained essentially unchanged. Pretreatment with celecoxib
      (0.1-1.0 mg kg(-1)) abolished not only thrombolysis by quinapril but also the
      quinapril-induced rise in plasma 6-keto-PGF1alpha. In cultured bovine aortic
      endothelial cells, perindoprilate (30 microM) increased cytosolic free calcium
      [Ca2+]i, but this effect was by three to four orders of magnitude weaker than
      that of bradykinin (Bk). In aortas of Wistar rats, the transcripts of COX-2 and
      PGI-S were overexpressed as compared to COX-1. Thus, in blood vessels of Wistar
      rats, the preferable route of the PGI2 generation might lead through the COX-2
      pathway. We conclude that in Wistar rats, ACE-I induces thrombolysis via
      accumulation of endogenous kinins over the endothelium and a subsequent
      activation of B2 receptors followed by the release of prostacyclin and nitric
      oxide. Thrombolysis by ACE-I seems to be mediated mainly through prostacyclin
      that is made by COX-2. It may well be that an increase in endothelial [Ca2+]i by
      ACE-I activates phospholipase A2, which supplies COX-2 with the substrate for
      making thrombolytic prostacyclin.

PMID- 14592557
TI  - Aspirin and the fibrinolytic response.
AB  - Apart from the anti-inflammatory action, aspirin (ASA) by inhibiting thromboxane
      A2 synthesis, decreases platelets activity and possesses the antithrombotic
      action. However, an ASA effect on fibrinolysis has not been yet finally
      established. Menon [Lancet 1 (1970) 364] reported increased fibrinolytic response
      in patients treated with high doses of ASA and this observation started a series
      of studies to find the relation between aspirin and fibrinolysis. This review
      comprises the results of those studies, divided into in vitro and in vivo, animal
      and human experiments. The results of our animal studies are also included. Data
      survey shows that the ASA effect on fibrinolysis depends on experimental
      conditions, the dose and the time of drug administration. The results of our
      study indicate the essential role of plasma components in the fibrinolysis
      regulation by ASA.

PMID- 14592558
TI  - COX and the control of the pulmonary circulation.
AB  - The lung possesses a low resistance circulation that must, at all times,
      accommodate the entire cardiac output. Moreover, to ensure proper oxygenation of
      hemoglobin, blood flow must be directed to well-ventilated lung units, i.e.,
      ventilation and perfusion must be matched. Cyclooxygenase (COX)-mediated
      arachidonic acid (AA) metabolites can influence both pulmonary vascular
      resistance and ventilation-perfusion matching. In isolated dog and rabbit lungs,
      ventilation of the right lung with oxygen (O2) and the left lung with nitrogen
      (N2) resulted in normal perfusion pressures and blood gas tensions. In both
      species, administration of COX inhibitors resulted in redistribution of blood
      flow from hypoxic alveoli (N2-ventilated lung) to the well-oxygenated alveoli (O2
      ventilated lung) and an increase in arterial oxygen tension, i.e., a COX-mediated
      AA metabolite or metabolites opposed hypoxic pulmonary vasoconstriction (HPV),
      but, by virtue of this activity, prevented optimal matching of ventilation with
      perfusion. The effects of COX inhibition were reversed by prostacyclin (PGI2).
      These findings are consistent with the hypothesis that COX-derived products of AA
      metabolism can influence ventilation-perfusion matching in the lung. Moreover,
      the results of studies in dogs suggest that one such metabolite of AA is PGI2.

PMID- 14592559
TI  - Relationships between fibrinogen, plasminogen activator inhibitor-1, and their
      gene polymorphisms in current smokers with essential hypertension.
AB  - BACKGROUND: To elucidate the role of some haemostatic gene polymorphisms and
      environmental factors, we studied fibrinogen (Fb), plasminogen activator
      inhibitor-1 (PAI-1), and tissue plasminogen activator (t-PA) levels with respect
      to Fb G455A and PAI-1 4G/5G gene polymorphisms in smokers and nonsmokers with
      essential hypertension. MATERIAL AND METHODS: The study was done in 90 patients
      (including 30 smokers) with essential hypertension (HT) and 40 controls
      (including 8 smokers). Fb and PAI-1 genotypes were PCR identified. The groups did
      not differ significantly as to genotype frequencies. RESULTS: When allele A455
      carriers were compared, HT patients had significantly higher Fb (p=0.015) and t
      PA levels (p=0.013). Comparison of 4G allele carriers (4G/4G homozygotes)
      revealed significantly higher Fb (p=0.045), PAI-1 (p=0.009), and t-PA levels
      (p=0.007) in HT patients than controls. Interactions of Fb and PAI-1 gene
      polymorphisms with smoking were disclosed in HT patients only. Allele A455
      carrying HT smokers compared with nonsmokers had significantly higher t-PA (12.1
      +/- 5.8 vs. 7.4 +/- 3.1 ng/ml; p=0.002) and tendency to higher Fb (3.36 +/- 0.74
      vs. 2.95 +/- 0.70 g/l; p=0.075) levels. Higher Fb levels were disclosed in 4G/4G
      smokers than nonsmokers (3.31 +/- 0.81 vs. 2.84 +/- 0.85 g/l; p=0.064). Finally,
      in smokers, significantly higher levels of PAI-1 were found in 4G/4G (42.1 +/-
      29.4 ng/ml) as compared with 4G/5G (18.6 +/- 13.7 ng/ml; p=0.025) and 5G/5G (14.4
      +/- 10.8 ng/ml; p=0.044) genotypes. CONCLUSIONS: Smoking potentiates the
      prothrombotic effect of allele A455 and PAI-1 4G/4G genotype in untreated
      essential hypertension, reflected by increased levels of haemostatic risk factors
      and accelerated progression of cardiovascular diseases.

PMID- 14592561
TI  - Aspirin and stroke prevention.
AB  - According to meta-analyses aspirin provides a relative reduction in the rate of
      major vascular events of 19% in patients with arterial disease in general,
      whereas for patients with ischaemic cerebrovascular disease this reduction is
      only 13%. The discrepancy may well result from pathophysiological differences and
      not from a play of chance. There is no proven difference in efficacy according to
      dose. The evidence for this equivalence is most compelling in the range between
      75 and 1300 mg daily, but still fairly convincing for doses between 30 and 50 mg.
      In contrast, side effects are clearly more frequent as the dose is higher. Other
      antiplatelet agents (sulfinpyrazone, ticlopidine, clopidogrel, dipyridamole,
      orally administered IIb/IIIa inhibitors) have no clear advantages over aspirin
      and in some cases definite disadvantages; the combination of aspirin and
      dipyridamole may be more efficacious than aspirin alone, but the evidence hinges
      on a single trial. If recurrent TIAs occur under treatment with aspirin, the
      rational response is not to change to a different antiplatelet agent, but to
      review the diagnosis and consider causes other than artery-to-artery embolism.
      Platelet aggregation can probably still occur despite complete acetylation of
      platelets, via pathways other than COX-1 inhibition, but in vitro aggregation
      tests are an unreliable measure.

PMID- 14592560
TI  - Aspirin and thrombinogenesis.

PMID- 14592562
TI  - Role of antiplatelet drugs in the prevention of cardiovascular events.
AB  - Antiplatelet drugs have an established place in the prevention of vascular events
      in a variety of clinical conditions, such as myocardial infarction, stroke and
      cardiovascular death. Both European and American guidelines recommend the use of
      antiplatelet drugs in patients with established coronary heart disease and other
      atherosclerotic disease. In high-risk patients, such as those with post-acute
      myocardial infarction (AMI), ischaemic stroke or transient ischaemic attack, and
      in patients with stable or unstable angina, peripheral arterial occlusive disease
      or atrial fibrillation, antiplatelet treatment may reduce the risk of a serious
      cardiovascular event by approximately 25%, including reduction of non-fatal
      myocardial infarction by 1/6, non-fatal stroke by 1/4 and cardiovascular death by
      1/6. Some data indicate that antiplatelet drugs may also have a role in primary
      prevention. In people who are aged over 65 years, or have hypertension,
      hypercholesterolaemia, diabetes, obesity or familial history of myocardial
      infarction at young age, aspirin may reduce both cardiovascular deaths and total
      cardiovascular events. Aspirin has been studied and used most extensively. It may
      exert its beneficial effect not only by acting on platelets, but also by other
      mechanisms, such as preventing thromboxane A2 (TXA2)-induced vasoconstriction or
      reducing inflammation. Indeed, experimental data show that low-dose aspirin may
      suppress vascular inflammation and thereby increase the stability of
      atherosclerotic plaque. Moreover, in human studies, aspirin seems to be most
      effective in those with elevated C-reactive protein levels. Vascular events,
      however, do occur despite aspirin administration. This may be due to platelet
      activation by pathways not blocked by aspirin, intake of drugs that interfere
      with aspirin effect or aspirin resistance. In the CAPRIE (Clopidogrel vs. Aspirin
      in Patients at Risk of Ischaemic Events) study, long-term clopidogrel
      administered to patients with atherosclerotic vascular disease was more effective
      than aspirin in reducing the combined risk of ischaemic stroke, myocardial
      infarction or vascular death. In the setting of coronary stenting, a double
      regimen including aspirin and ticlopidine or clopidogrel has proved more
      effective in the prevention of in-stent thrombosis than aspirin alone. Chronic
      oral administration of the inhibitors of platelet membrane receptor GP IIb/IIIa
      has been largely disappointing.

PMID- 14592563
TI  - The real dimension of analgesic activity of aspirin.
AB  - Aspirin, despite being 100-years old, even in the era of evidence-based medicine,
      remains a valuable analgesic. Results of randomized trials have shown that it is
      as well effective and safe as other analgesics in relieving mild pain and can be
      used in the first-line therapy of migraine.

PMID- 14592564
TI  - Decreased plasma concentration of a novel anti-inflammatory protein--adiponectin-
      in hypertensive men with coronary artery disease.
AB  - AIMS: Recent studies indicate that adiponectin may have anti-inflammatory and
      anti-atherogenic properties, suggesting that hypoadiponectinemia can play a role
      in the pathogenesis of cardiovascular disease. Therefore the aim of the study was
      to assess plasma adiponectin concentration in hypertensive male patients with
      coronary artery disease (CAD). Associations of adiponectinemia with other
      cardiovascular risk factors were also analysed. METHODS AND RESULTS: The study
      included 99 consecutive male patients (median age 57 years) with hypertension and
      CAD who at the same time underwent coronary and renal angiography. The control
      group consisted of 62 BMI-matched healthy male blood donors (median age 48
      years). Plasma adiponectin level was significantly lower in the CAD group as
      compared to the control group (4.01 +/- 0.18 vs. 4.88 +/- 0.24 microg/ml;
      p<0.01). There were no differences in plasma adiponectin concentration between
      hypertensive CAD patients with and without atherosclerotic renal artery stenosis.
      In the CAD group plasma adiponectin concentration correlated with levels of
      creatinine (r=0.56; p<0.001), HDL cholesterol (r=0.24; p<0.05), BMI (r=-0.33;
      p<0.001), glucose (r=-0.22; p<0.05) and triglycerides (r=-0.25; p<0.05). No
      correlation was found between plasma adiponectin and homocysteine concentrations.
      In a multivariate stepwise logistic regression model increasing concentrations of
      adiponectin were independently and significantly associated with a lower risk of
      CAD (OR 0.58 95% CI 0.42-0.81 p<0.001). CONCLUSIONS: Our results showed decreased
      plasma adiponectin concentration in the studied group of hypertensive men with
      CAD as compared to normotensive healthy subjects. This may suggest that decreased
      plasma adiponectin concentration is associated with a higher risk of CAD.

PMID- 14592565
TI  - Preliminary exploration of the relationships between soil characteristics and PAH
      desorption and biodegradation.
AB  - Desorption and biodegradation of pyrene (PYR) were investigated and their
      relationships to soil characteristics were addressed. The results indicated that
      maximum achievable desorption was 30.2, 10.4, and 1.0 mg/kg for soils that had
      1.7, 2.2, and 4.4 wt.% of expandable clays (smectite and vermiculite),
      respectively. Neither dissolved organic matter (DOM) nor total clay amounts made
      a good prediction of the desorption trend. Subsequently, the ease of desorption
      facilitated a faster aqueous biodegradation rate. The slowest aqueous
      biodegradation rate, 0.02 l/h, was achieved for the soil system that had the
      greatest amount of expandable clays, whereas the soil containing 1.7% expandable
      clays only achieved 0.73 l/h. The soil with 2.2% expandable clays depicted 0.41
      l/h of aqueous biodegradation rate. A good linear correlation was obtained
      between maximum achievable desorption and aqueous biodegradation rate
      (R(2)=0.92). Soil analysis revealed that the total (soil+water) biodegradation
      reached was 65%, 78.3%, and 81.8% of the initial concentration (100 mg/kg) for
      the sandy clay loam (Colombian), sandy loam (Ohio), and silty loam (New Mexico)
      soils, respectively. This biodegradation extent was also in good agreement of
      expandable clay amount. Although aqueous PYR bioavailability was limited due to
      the strong association with the expandable clays, microbial movement and adhesion
      to those clays seemed to result in a great extent of the soil-phase
      biodegradation.

PMID- 14592566
TI  - Chemical speciation and phytoavailability of Zn, Cu, Ni and Cd in soil amended
      with fly ash-stabilized sewage sludge.
AB  - A sequential extraction method was used to determine chemical forms of Cu, Zn, Ni
      and Cd in fly ash-stabilized sludge. A loamy acid soil amended with fly ash
      stabilized sludge was used to grow corn under greenhouse conditions. Sewage
      sludge amended with coal fly ash can reduce the availability of Cu, Zn, Ni and Cd
      in the sludge. Increasing fly ash amendment rate significantly reduced DTPA
      extractable Cu, Zn, Ni and Cd concentrations. Percentages of Cu, Zn and Ni in
      residual fraction increased with an increase in fly ash amendment rates. Majority
      of Cu was associated with organic form, but Zn and Ni were associated with Fe-Mn
      oxide and residual forms. Addition of ash-amended sludge to soil significantly
      increased dry mass of corn. With coal fly ash amendment rate increasing,
      concentrations of Zn and Cu in shoot tissues of corn decreased significantly, but
      concentrations of Cd and Ni did not change significantly. Significant
      correlations were found between concentrations of Cu and Zn in corn shoot and
      oxide and total Cu fractions, and all chemical fractions of Zn in fly ash
      stabilized sludge, respectively. Hence, ash amendment significantly reduced the
      availability of heavy metals by chemical modification of their chemical
      speciation into less available forms.

PMID- 14592567
TI  - Relationships between spatial and temporal variabilities in airborne metal
      distributions in Won Ju City, Korea.
AB  - The relationship between temporal and spatial factors in controlling the metal
      distribution characteristics was investigated using the monthly metal
      concentration data collected from four distinctive sampling sites (grassland,
      residential, commercial, and industrial site) of Won Ju City, Kang Won province
      for approximately 4-year periods between 1991 and 1995. In order to compare the
      relative role of spatial and temporal factors, two-factor analysis of variance
      (ANOVA) was applied to these data sets. For the application of this method,
      temporal factors were investigated in terms of both annual and seasonal basis.
      The results of our data analysis indicated several interesting aspects of metal
      to-metal distribution behavior such that: (1) Pb, Fe, and Cu tend to exhibit
      strong variabilities in both spatial and temporal scale, (2) the distribution
      variabilities for Mn are almost negligible in both temporal and spatial scale,
      (3) Cd is more variable in temporal, rather than spatial, sense, and (4) Cr and
      Ni can exhibit more variable patterns depending on temporal scale selected for
      data analysis. On the basis of this study, the relative roles of spatial and
      temporal factors are described in relation to each other and to different metal
      species.

PMID- 14592568
TI  - Estimation of septic tank setback distances based on transport of E. coli and F
      RNA phages.
AB  - Setback distances between septic tank systems and the shorelines of Lake Okareka,
      New Zealand were determined from model simulations for a worst-case scenario,
      using the highest hydraulic conductivity and gradient measured in the field,
      removal rates of the microbial indicators (Escherichia coli and F-RNA phages)
      determined from a column experiment, and maximum values of the design criteria
      for the disposal system, and assuming an absence of an unsaturated zone, a
      continuous discharge of the raw effluent from a failed or non-complying treatment
      system (both indicators at concentrations of 1x10(7) counts/100 ml) into the
      groundwater and no sorption of pathogens in the aquifer. Modelling results
      suggest that the minimal setback distances were 16 m to satisfy the New Zealand
      Recreational Water Quality Guidelines for E. coli <126 per 100 ml (Ministry for
      the Environment, 1999) and 48 m to meet the Drinking-Water Standards for New
      Zealand 2000 for enteric virus <1 per 100 l (Ministry of Health, 2000). These
      distances may be applicable for other lakeshores in pumice sand aquifers with
      groundwater velocities <7 m/day. Findings of laboratory column and batch
      experiments provided an insight into the microbial attenuation and transport
      processes in pumice sand aquifers. Bacterial removal was predominately through
      filtration (87-88%) and partially by die-off (12-13%), while viral removal was by
      both die-off (45%) and filtration (55%). In addition, microbial die-off in
      groundwater without aquifer material (i.e., free microbes) was much lower than
      die-off in groundwater with aquifer material (i.e., sorbed microbes) and
      contributed only 2-6% to the total removal. This implies that the setback
      distances estimated from die-off rates for the free microbes, determined in the
      laboratory without considering aquifer media and other removal processes, which
      are often reported in the literature, could be larger than necessary.

PMID- 14592569
TI  - Genotoxic and biochemical responses in caged eel (Anguilla anguilla L.) after
      short-term exposure to harbour waters.
AB  - European eel (Anguilla anguilla L.) were caged and exposed in situ for 8 and 48 h
      to the Aveiro offward fishing harbour water (HW) and to clean seawater under
      laboratory conditions (Control). Eel liver biotransformation (Phase I) was
      measured as ethoxyresorufin-O-deethylase (EROD) activity, cytochrome P450 (P450)
      and glutathione S-transferase (GST) activity (Phase II). Genotoxic responses were
      determined as blood, liver and kidney DNA strand breaks as well as erythrocytic
      nuclear abnormalities (ENAs). HW failed to significant increase liver EROD, GST
      activities and ENA frequency. Nevertheless, P450 content was significantly
      increased after 8 and 48 h exposure. Genotoxicity measured as DNA integrity
      decrease was found in blood after 8 and 48 h exposure to HW, whereas in liver and
      kidney, it was observed after 48 h exposure to HW. Blood, kidney and liver
      genotoxicity may be due to the presence of polycyclic aromatic hydrocarbons
      (PAHs) which are genotoxic compounds and the main HW organic contaminants.

PMID- 14592570
TI  - Asbestos exposure among Seoul metropolitan subway workers during renovation of
      subway air-conditioning systems.
AB  - Air quality in underground spaces has seldom been evaluated in Korea.
      Accordingly, the current study recently evaluated asbestos exposure among Seoul
      metropolitan subway workers during the renovation of the subway's air
      conditioning system. To identify possible routes of asbestos exposure, suspected
      sources, including gaskets, ceiling boards, ceiling materials, and dust settled
      inside ducts, were all sampled. Personal air samples were also taken to evaluate
      any asbestos exposure during the renovation. The asbestos fibers found in the
      samples were analyzed using a transmission electron microscope (TEM) equipped
      with an energy dispersive X-ray analyzer (EDX). Twelve out of eighteen bulk
      samples contained asbestos, the majority of which was chrysotile fibers. Asbestos
      was detected in 9 out of 72 personal air samples and the level ranged from 0.003
      to 0.02 fibers/cm(3). While asbestos levels were below Korean occupational limit
      of 2 fibers/cm(3), they were still detectable and therefore further monitoring
      would be appropriate.

PMID- 14592571
TI  - Heavy metal distribution and controlling factors within coastal plain sediments,
      Bells Creek catchment, southeast Queensland, Australia.
AB  - Bells Creek catchment in southeast Queensland (Australia) is a non-industrialised
      coastal plain limited to small settlements and agricultural land. A study was
      initiated to examine elevated metal concentrations and to assess horizontal and
      vertical distribution of those elements. Ninety-nine samples were analysed for
      Cr, V, Ni, Cu, Zn, Pb, As, Fe, Mn and Al. Total organic carbon, sulfur content
      and mineralogy of samples along with land-use practices across the catchment were
      used to identify processes which influence metal distribution. A comparison
      between metal concentration within the study area and mean heavy metal content of
      standard sandstone showed that except for Mn, all other metals showed elevated
      levels throughout the catchment. When metal concentrations were compared to
      parent bedrock, however, it was concluded that elevated levels are likely to be
      natural. A normalisation procedure was applied to the data set and this analysis
      validated that elevated trace metal concentrations in most samples are not due to
      artificial contamination. While surficial estuarine sediments were only enriched
      in V, soils were dominantly enriched in Cr, Zn and V. Overall, geochemistry and
      mineralogy of the samples show the effect of both natural and anthropogenic
      inputs to the catchment, however, natural processes are more dominant than
      anthropogenic inputs in concentrating metals.

PMID- 14592573
TI  - Assessment of arsenic and heavy metal concentrations in water and sediments of
      the Rio Grande at El Paso-Juarez metroplex region.
AB  - The Rio Grande located along the US-Mexico border is affected by anthropogenic
      activities along its geographical course. Runoff and wind deposition of smelting
      residues may contribute to the pollution of the Rio Grande in the El Paso-Ciudad
      Juarez area. Few studies have addressed the presence or impacts of heavy metals
      or arsenic in this ecosystem. This study reports a survey of heavy metals (Cr,
      Cu, Cd, Ni, Pb, and Zn) and arsenic (As) in water and sediments of the Rio Grande
      collected from seven sites in the El Paso-Juarez region. Since water quality
      influences metal content in water, physical (temperature, flow and conductivity),
      and chemical (pH, dissolved oxygen, nitrates, alkalinity, and water hardness)
      parameters were measured at each site. Arsenic and heavy metal levels were
      determined using Inductively Couple Plasma (ICP) emission spectroscopy following
      EPA procedures. Zinc and lead were found as both total and dissolved metals in
      most of the samples, with concentrations of total recoverable metals reaching up
      to 105 and 70 microg/l, respectively. Most metals were found in sediment samples
      collected from four of seven sites. The highest Cu concentration (35 mg/l) was
      found at the American Dam site. Concentrations of metals found through this
      survey will be used as a reference for future studies in monitoring arsenic,
      heavy metals, and their impacts in the Rio Grande.

PMID- 14592572
TI  - Heavy metals in fish (Solea vulgaris, Anguilla anguilla and Liza aurata) from
      salt marshes on the southern Atlantic coast of Spain.
AB  - Comparisons were made of metal concentrations in water and sediment with those in
      the muscle and livers of three species of fish caught in four seawater reservoirs
      (two in the Odiel estuary and two in the Bay of Cadiz). The concentrations of a
      large number of metals in the water, sediment and fish were higher in the Odiel
      reservoirs than in those in Cadiz. We found high metal-enrichment factors in the
      livers as compared to muscle (over 100 for Fe and Cu and around 5 for Zn, Ni, Cd
      and Pb). The three fish species showed differences in metal content. For example,
      eels accumulated more metals in muscle and grey mullet in the liver. The metal
      levels found in muscle in the three species were below the legal limits for human
      consumption, although Cu in the liver was above the limit in the three species
      taken from the Odiel reservoirs, and Zn levels in liver were over the maximum in
      eels from one of the Odiel marshes. Significant correlations (p<0.05) were
      obtained for the levels of numerous metals in water, sediment and fish.

PMID- 14592575
TI  - Determination of heavy metal concentrations in street dusts in Istanbul E-5
      highway.
AB  - Components and quantity of street dust are environmental pollution indicators
      especially in big cities. Street dust is generally composed of car exhaust gas
      originated particles and wind-transported particles. Heavy metals, which are
      found in street dust, such as Pb, Cu, Mn, Zn, Cd and Ni are significant for
      environmental pollution. According to the kind of vehicle in traffic, quantity
      and type of heavy metals vary in street dust. The use of leaded gasoline gives a
      boost to the importance of lead level especially in street dust even at the start
      of 21st century. These metals possess bioaccumulation property, and the
      possibility of the amount of these metals reaching a critical value and
      threatening human health increases the importance of this issue. In this study,
      street dusts have been collected from E-5 Highway from Topkapi to Avcilar regions
      that spans about 18 km in Istanbul, Turkey, and Pb, Cu, Mn, Zn, Cd and Ni
      concentrations have been detected in street dust. Twenty-two street dust samples
      were taken from a total of 22 different points at previously decided 14 main
      areas. Analyses were conducted using Leeds Public Analyst method. According to
      the results of this study, Pb, Cu and Zn concentrations in E-5 Highway between
      Topkapi and Avcilar region in Istanbul were higher than maximum concentration
      levels of these heavy metals in normal soil. This situation indicates that there
      is heavy metal pollution in the inspected area in E-5 Highway in Istanbul.

PMID- 14592574
TI  - Effects of forms and rates of potassium fertilizers on cadmium uptake by two
      cultivars of spring wheat (Triticum aestivum, L.).
AB  - A greenhouse pot experiment was conducted to study the influence of potassium
      fertilizers in different forms and rates on cadmium (Cd) uptake by two cultivars
      of spring wheat (Triticum aestivum, L.): Brookton and Krichauff. Potassium
      fertilizers were added to soil at four levels: 0, 55, 110 and 166 mg K kg(-1)
      soil as KNO(3) (N), KCl (C) or K(2)SO(4) (S). CdCl(2) was added to all the
      treatments at a uniform rate equivalent to 15 mg Cd kg(-1) soil. Plant shoot and
      root dry weights (DW) of both cultivars were reduced significantly by the
      addition of K-fertilizer in C and S treatments but there were only marginal
      changes in the N treatments. The Cd concentrations in shoots and whole plants
      increased significantly (P<.001) with increasing K addition, from 37.5 to 81.4 mg
      kg(-1) and from 42.9 to 86.8 mg kg(-1) for Brookton and Krichauff, respectively.
      However, no obvious effect was observed in the N treatments, except for the
      highest K level (K3) where there was a sharp increase in Cd concentration
      compared to the lower additions. Forms of K-fertilizers significantly influenced
      the Cd concentrations in plant shoots and roots (P<.001), but there was no
      significant difference between C and S treatments. This experiment showed that
      anions Cl(-) and SO(4)(2-) increase Cd uptake by plants, which can be interpreted
      as Cl(-) and SO(4)(2-) complexing readily with Cd(2+) and thereby increasing the
      bioavailability of Cd(2+) in soils. The effect of potassium itself on plant
      uptake of Cd was also observed. We suggest that when applying potassium
      fertilizer to Cd-contaminated soils, the forms and rates should be considered.

PMID- 14592576
TI  - Comparison of the radiological dose from the Cerro Grande fire to a natural
      wildfire.
AB  - Since the Cerro Grande fire burned portions of a Department of Energy facility
      where nuclear weapons research occurs, it is important to determine if the fire
      posed greater risk to the public than a natural fire. All wildfires release
      radioactive as well as other toxic pollutants into the atmosphere. Thus, it is
      important to determine if the radioactive air emissions from the Cerro Grande
      fire were statistically different than those from a natural wildfire,
      specifically the Viveash fire.

PMID- 14592577
TI  - Anguilla anguilla L. plasma cortisol, lactate and glucose responses to abietic
      acid, dehydroabietic acid and retene.
AB  - Anguilla anguilla L. were exposed to 0, 0.1, 0.3, 0.9 and 2.7 microM abietic
      (AA), dehydroabietic (DHAA) acids and retene (Re) during 8, 16, 24 and 72 h. The
      eels plasma cortisol, glucose and lactate were measured. A significant decrease
      in plasma cortisol was observed at 72 h exposure to 0.9 and 2.7 microM Re. DHAA
      (0.1 microM) significantly decreased plasma cortisol in eels after 8 and 24 h
      exposure. However, a significant plasma cortisol increase was found after 16 h,
      2.7 microM AA exposure and after 24 h exposure to 0.1 microM and 2.7 microM AA.
      Furthermore, 72 h exposure to 0.9 microM AA also induced a plasma cortisol
      increase. A general rise in plasma glucose was detected after all exposure
      periods to Re. The plasma lactate also increased after 72 h exposure to 2.7
      microM AA and after 8 h exposure to 0.1 microM DHAA.

PMID- 14592578
TI  - Fractionation studies and bioaccumulation of sediment-bound heavy metals in
      Kolleru lake by edible fish.
AB  - Kolleru lake is the largest fresh water lake in the districts of East and West
      Godavari of Andhra Pradesh, India. Many anthropogenic sources contribute to the
      heavy metal pollution in the lake and the bioaccumulation of heavy metals in fish
      helps in assessing the aquatic pollution. Total contents and fractionation of
      selected heavy metals, viz., Zn, Cu, Cd, Pb, Cr, Ni and Co were measured in
      sediment sample and three edible fish. The investigation aimed at revealing
      differences in the accumulation pattern of heavy metals in fish inhabiting
      sediments characterized by varying metal bioavailability. The metal
      concentrations were found to be greater than the background concentrations of
      sediments indicating the anthropogenic origin of metals. Good recovery values
      were obtained for metal contents in sediments and fish. Large fractions of Zn, Cd
      and Cu were associated with mobile fraction of sediment and showed greater
      bioaccumulation in fish whereas Ni and Co were least mobilisable. The results
      clearly indicate that the fish of Kolleru lake are contaminated with metals and
      not advisable for human consumption.

PMID- 14592579
TI  - The drugs we deserve.

PMID- 14592580
TI  - Questioning the ubiquity of outpatient endometrial sampling in the management of
      menstrual disorders.

PMID- 14592581
TI  - The development of a national database of the results of surgery for urinary
      incontinence in women.
AB  - OBJECTIVE: To describe the development of a national network, database and
      reporting of data from a short-form questionnaire recording the severity of
      symptoms, quality of life and objective outcome values pre- and post-operatively,
      in women with stress and mixed incontinence. DESIGN: A prospective descriptive
      study. SETTING: Twenty-three Norwegian departments of gynaecology. PARTICIPANTS:
      Eight hundred and eighty-three women with stress and mixed incontinence. METHODS:
      A short-form questionnaire was used to record the severity of symptoms, quality
      of life and objective outcome values pre- and post-operatively, in women with
      stress and mixed incontinence. Type of operation, the performance of a combined
      vaginal prolapse operation and an incontinence procedure and complications were
      recorded. The questionnaires were scanned and data were transferred to a national
      database. Twice a year the participating departments received a report where
      their own data were compared with the national average. MAIN OUTCOME MEASURES:
      Pre- and post-operative Stress, Urge and Quality of Life Indices, Satisfactioin
      with the operation. Post-operative mean Stress, Urge and Quality of Life Indices,
      leakage during stress test, and satisfaction with the operation, related to
      number of operations performed by each surgeon. RESULTS: Eighty-four percent of
      the operations performed were with the tension-free vaginal tape operation and
      13% were abdominal Burch colposuspensions. The post-operative Stress and Urge
      Incontinence Indices and Quality of Life Index and all the objective outcome
      values except for the mean voiding volume were significantly lower than they were
      pre-operatively. Eighty-four percent of the women were very satisfied, 8% were
      moderately satisfied, 2% were neither satisfied nor dissatisfied, 3% were
      moderately dissatisfied and 2% were very dissatisfied with the operation. Women
      who had a tension-free vaginal tape operation performed were significantly more
      satisfied, were leaking significantly less, had significantly lower stress
      incontinence and quality of life indices and had significantly less superficial
      infections post-operatively than women who had had a Burch colposuspension.
      Surgeons performing fewer than 25 operations had a large variation in their
      results. CONCLUSION: A large number of Norwegian gynaecological departments are
      reporting to the database. The questionnaire and the objective outcome values are
      well suited to record the effect of incontinence operations and to make
      comparisons between surgical procedures, surgeons and departments.

PMID- 14592582
TI  - The development of a questionnaire to measure the severity of symptoms and the
      quality of life before and after surgery for stress incontinence.
AB  - OBJECTIVES: To develop and validate a short questionnaire recording the severity
      of symptoms and the quality of life, pre- and post-operatively, in women
      undergoing surgery for stress incontinence. DESIGN: The questionnaire was
      designed from previously designed questionnaires and pilot studies. In this
      study, it was tested for validity and reliability using standard psychometric
      techniques. Data from the questionnaire are reported to a national database,
      which generates reports for comparison of surgical procedures, departments and
      surgeons. SETTING: Tertiary referral urogynaecology units at Baerum and Aker
      Hospitals, Norway, and 22 Norwegian departments of gynaecology. POPULATION: Fifty
      and 65 women with stress incontinence from Baerum and Aker hospitals,
      respectively, and 628 women with stress incontinence from 22 Norwegian
      departments of gynaecology. METHODS: Stress Incontinence, Urge Incontinence and
      Quality of Life Indices were constructed. Internal consistency of the indices was
      measured by Cronbach's alpha and test-retest reliability by Bland-Altman plots.
      Stress Incontinence Index was tested against stress test and Urge Incontinence
      Index and Stress Incontinence Index were tested against the 24-hour pad test.
      Quality of Life Index was tested against a part of the King's College Hospital
      Quality of Life Questionnaire. MAIN OUTCOME MEASURES: Face and content validity.
      Missing values of the questionnaire. Reliability and internal consistency.
      Criterion validity. RESULTS: The 628 women completed a mean of 98.2% of all the
      questions. The content validity was good. The reliability was good in terms of
      test-retest reliability and internal consistency. The criterion validity of
      stress and urge incontinence was tested against the stress and 24 hour pad tests.
      The correlation between the indices and the objective tests was moderate. The
      correlation between the Quality of Life Index and the physical and social part of
      the previously validated King's College Hospital questionnaire was good.
      CONCLUSIONS: The questionnaire is easy to understand and complete and is a valid
      and reliable instrument for assessment of the symptoms of incontinence and the
      quality of life. Pre- and post-operative evaluation of women with stress
      incontinence was performed in a standardised setting in 22 of the 37 Norwegian
      departments and the reporting to a national database was successful. Comparison
      of surgical procedures, departments and surgeons is possible.

PMID- 14592583
TI  - The usefulness of ultrasound assessment of amniotic fluid in predicting adverse
      outcome in prolonged pregnancy: a prospective blinded observational study.
AB  - OBJECTIVE: To determine whether a single ultrasound scan at or beyond 40 weeks of
      gestation to detect a single deepest pool of amniotic fluid <2 cm and amniotic
      fluid index (AFI) <5 cm is clinically useful in the prediction of subsequent
      adverse pregnancy outcome. DESIGN: A prospective double blind cohort study.
      SETTING: A university teaching hospital delivering approximately 6000 women
      annually. POPULATION: One thousand and five hundred and eighty-four pregnant
      women at or beyond 40 weeks of gestation. METHODS: Ultrasound assessment of
      liquor to detect the single deepest pool of amniotic fluid and derive the AFI at
      or after 40 weeks of gestation. MAIN OUTCOME MEASURES: Perinatal death, meconium
      aspiration, birth asphyxia, intervention in labour for fetal distress, a cord
      arterial pH <7 and admission to the neonatal unit. RESULTS: An AFI <5 cm but not
      a single deepest pool <2 cm was significantly associated with birth asphyxia or
      meconium aspiration. An AFI <5 cm was also significantly associated with
      caesarean section for fetal distress in labour, a cord arterial pH <7 at delivery
      and low Apgar scores. Despite there being a statistically significant association
      with adverse outcomes the sensitivity of AFI was low at 28.6%, 12% and 11.5% for
      major adverse outcome, fetal distress in labour or admission to the neonatal
      unit, respectively. CONCLUSIONS: The AFI is superior to a measure of the single
      deepest pool as an assessment of the fetus at or after 40 weeks but has a poor
      sensitivity for adverse pregnancy outcome. Routine use is likely to lead to
      increased obstetric intervention without improvement in perinatal outcomes.

PMID- 14592584
TI  - Maternal mortality: only 42 days?
AB  - OBJECTIVE: A maternal death is defined by WHO as 'the death of a woman while
      pregnant or within 42 days of termination of pregnancy em leader '. The origin of
      the 42 days is no longer clear. In developing countries, the burden imposed by
      pregnancy and birth on a woman's body may extend beyond 42 days as pregnancy
      related anaemia can persist for longer and vaginal haemorrhaging and risk of
      infections are not necessarily over after six weeks. We therefore examined
      duration of excess mortality after delivery in rural Guinea-Bissau. DESIGN: In a
      prospective cohort study, we followed 15,844 women of childbearing age with
      biannual visits over a period of six years, resulting in a total of 60,192 person
      years-at-risk. To establish cause and timing in relation to termination of
      pregnancy, verbal autopsy was carried out for all deaths. Mortality rates were
      calculated for short time intervals after each delivery or miscarriage. RESULTS:
      During the observation period we registered 14,257 pregnancies and 350 deaths.
      One hundred and ninety-four deaths followed termination of a registered pregnancy
      and thus were eligible for the analysis. Eighty-two deaths occurred during the
      first 42 days after delivery/miscarriage. A further 16 women died in the period
      from 43 to 91 days after parturition, 16 between 92 and 182 days and 18 between
      183 and 365 days after delivery. Compared with baseline mortality 7-12 months
      after delivery, women who had recently delivered had 15.9 times higher mortality
      (95% CI 9.8-27.4). From days 43 to 91 the mortality was still significantly
      elevated (RR = 2.8 [1.4-5.4]). CONCLUSION: Where living conditions are harsh,
      pregnancy and delivery affect the health of the woman for more than 42 days.
      Using the WHO definition may result in an under-estimation of the pregnancy
      related part of the reproductive age mortality. Extending the definition of
      maternal death to include all deaths within three months of delivery may increase
      current estimates of maternal mortality by 10-15%.

PMID- 14592585
TI  - Low plasma volume following pregnancy complicated by pre-eclampsia predisposes
      for hypertensive disease in a next pregnancy.
AB  - OBJECTIVE: A large number of women with a history of pre-eclampsia/HELLP have a
      low plasma volume at least six months postpartum. The objective of this study was
      to determine whether a low plasma volume in formerly pre-eclamptic women and
      HELLP patients is associated with an increased risk for recurrent hypertensive
      complications in a next pregnancy. DESIGN: Prospective observational study.
      SETTING: Tertiary obstetric centre. SAMPLE: Formerly pre-eclamptic women and
      controls. METHODS: In 316 women with a history of pre-eclampsia and/or HELLP, we
      measured, plasma volume along with haemodynamic, metabolic and haemostatic
      variables at least six months postpartum. A group of 22 healthy parous controls
      was used as a reference. After standardising plasma volume for body mass index,
      women were subdivided into normotensive and normal plasma volume (n = 199),
      normotensive and low plasma volume (n = 76) and hypertensive (n = 41) subgroups,
      which were compared for demography, clinical parameters and course of a next
      pregnancy. MAIN OUTCOME MEASURES: Recurrent hypertensive disease of pregnancy.
      RESULTS: Relative to the normal plasma volume subgroup, normotensive women in the
      low plasma volume subgroup have a higher body mass index, a lower total vascular
      compliance and a shorter estimated systemic circulation time. They have a higher
      HOMA index and higher fasting triglyceride levels. In normotensive and
      hypertensive former patients alike, low plasma volume is associated with a higher
      recurrence of hypertensive complications in a next pregnancy compared with
      normotensive women with normal plasma volume. CONCLUSION: Low plasma volume in
      normotensive women with a history of pre-eclampsia and/or HELLP is associated
      with overweight, reduced vascular compliance and insulin resistance and a
      predisposition for recurrent pre-eclampsia and HELLP syndrome in a next
      pregnancy.

PMID- 14592586
TI  - Assessment of fetal liver volume and umbilical venous volume flow in pregnancies
      complicated by insulin-dependent diabetes mellitus.
AB  - OBJECTIVES: To determine fetal liver volume and its relation with umbilical
      venous volume flow and maternal glycosylated haemoglobin (HbA1c) in pregnancies
      complicated by diabetes mellitus type I. DESIGN: A cross sectional matched
      control study. Obstetric out patient clinic, Erasmus MC-University Medical
      Centre, Rotterdam. POPULATION: Data from fetuses of diabetic women (n = 32; 18-36
      weeks) were compared with data from normal controls (n = 32) matched for
      gestational age. METHODS: Umbilical venous cross sectional area (mm(2)) and time
      averaged velocity (mm/s Doppler) were determined for calculation of volume flow
      (mL/min) and flow per kilogram fetal weight (mL/min/kg). Umbilical artery
      pulsatility index was determined. Fetal liver volume measurements were obtained
      using a Voluson 530-D. MAIN OUTCOME MEASURES: Fetal liver volume, umbilical
      venous volume flow and downstream impedance. RESULTS: A statistically significant
      difference between fetuses of diabetic women and normal controls was found for
      liver volume (mean [SD]: 45.9 [34.0] vs 38.3 [28.7] mL), abdominal circumference
      (22.2 [6.6] vs 21.3 [5.6] cm), estimated fetal weight (1162 [898] vs 1049 [765]
      g) and fetoplacental weight ratio (0.22 vs 0.19) and liver volume/estimated fetal
      weight ratio (4.13% [0.007] vs 3.62% [0.009]). Umbilical venous volume flow
      (mL/min) and umbilical artery pulsatility index were not essentially different
      between the two study groups, but umbilical venous volume flow per kilogram fetal
      weight was lower (P < 0.05) in the diabetes group (94.3 [26.1] mL/min kg)
      compared with normal controls (109.5 [28.0] mL/min/kg). A positive correlation
      existed between fetal liver volume and maternal HbA1c (P = 0.002). CONCLUSIONS:
      Measurement of fetal liver volume by three-dimensional ultrasound may play a role
      in identifying fetal growth acceleration in diabetic pregnancies. Fetal liver
      volume increase is positively related to maternal HbA1c levels reflecting degree
      of maternal glycemic control. Fetal liver volume normalised for estimated fetal
      weight is significantly higher in the fetuses of diabetic women. In the present
      study, umbilical venous volume flow and fetoplacental downstream impedance are
      not different between diabetic and normal pregnancies.

PMID- 14592588
TI  - FE 200 440: a selective oxytocin antagonist on the term-pregnant human uterus.
AB  - OBJECTIVE: To compare a newly developed oxytocin antagonist, FE 200 440, with
      atosiban and ANTAG III, as to potency and selectivity of inhibitory effects on
      oxytocin- and vasopressin-induced myometrial responses. FE 200 440 has high
      affinity for the human cloned oxytocin receptor, approximately 300-fold that for
      the vasopressin V(1a) receptor, whereas atosiban binds well to both receptors.
      DESIGN: In vitro study of human myometrial contractility. The Research Laboratory
      of the Department of Obstetrics and Gynecology, Lund University Hospital, Sweden.
      PARTICIPANTS: Forty-seven term-pregnant women not in labour who were delivered by
      caesarean section. INTERVENTIONS: Concentration-response curves with oxytocin and
      arginine vasopressin on isolated myometrial strips were recorded in control
      experiments, in the presence of atosiban in concentrations of 25, 250 and 750
      nmol/L, and after pretreatment with ANTAG III and FE 200 440, both in
      concentrations of 2.5, 25 and 250 nmol/L.pA(2) values (i.e. an index of
      inhibitory action). RESULTS: With oxytocin as the agonist, the median pA(2)
      values for atosiban, ANTAG III and FE 200 440 were 10.6, 9.5 and 8.3,
      respectively. With vasopressin as the agonist, the pA(2) values for atosiban and
      ANTAG III were 8.8 and 8.7, whereas no inhibitory effect of FE 200 440 was seen
      in five out of six experiments. CONCLUSION: The new analogue FE 200 440 is a
      selective oxytocin antagonist and, in contrast to atosiban and ANTAG III, has
      practically no effect on vasopressin-induced contractions of isolated term
      pregnant human myometrium.

PMID- 14592587
TI  - Sexual psychophysiology and effects of sildenafil citrate in oestrogenised women
      with acquired genital arousal disorder and impaired orgasm: a randomised
      controlled trial.
AB  - OBJECTIVE: Some postmenopausal women lose genital sexual responsivity despite
      preserved subjective sexual arousal from non-genital stimuli. When oestrogen
      replacement is without benefit, both the underlying pathophysiology and
      management of this acquired genital female sexual arousal disorder are unclear.
      We aimed to study the effect of sildenafil on sexual arousal and orgasmic
      functioning of such women. Secondly, we aimed to explore the concordance between
      a detailed historical assessment of genital response in real life, with
      laboratory vaginal photoplethysmographic assessment of genital vasocongestion.
      DESIGN: Session one consisted of a semi-structured clinical interview to assess
      real life sexual arousal. Session two employed vaginal pulse amplitude and self
      report questionnaire assessment of erotica-induced sexual arousal. Sessions three
      and four were a randomised, double-blind, placebo-controlled crossover
      administration of sildenafil on orgasm latency, intensity, perception of genital
      congestion and subjective arousal to erotica plus clitoral vibrostimulation.
      SETTING: University associated Sexual Medicine Clinic and Psychophysiology
      Laboratory. SAMPLE: Volunteer sample of 34 oestrogenised postmenopausal women
      with acquired genital female sexual arousal disorder and impaired orgasm.
      METHODS: Sildenafil (50 mg) or placebo administered over two laboratory sessions.
      MAIN OUTCOME MEASURES: Orgasm latency and intensity during drug sessions;
      subjective and psychophysiological sexual arousal during photoplethysmography
      session. RESULTS: The erotic video significantly increased subjective sexual
      arousal in all women. Vaginal pulse amplitude responses varied from robust to
      absent. Although across all women, sildenafil improved neither arousal nor
      orgasm, subsequent analyses comparing high versus low vaginal pulse amplitude
      responders revealed significantly reduced latency to orgasm, and increased
      subjective sexual arousal and perception of genital arousal in the latter group
      of women. CONCLUSION: The data suggest that oestrogenised postmenopausal women
      with genital female sexual arousal disorder and orgasmic impairment based only on
      clinical assessment do not benefit from sildenafil. However, the
      photoplethysmograph had predictive value-those women showing low vaginal pulse
      amplitude response benefited from sildenafil compared with women with a higher
      response. Thus, oestrogenised women diagnosed with acquired genital female sexual
      arousal disorder may be a heterogeneous group and the photoplethysmograph might
      be useful in their further characterisation.

PMID- 14592590
TI  - Ligneous conjunctivitis and the cervix.

PMID- 14592589
TI  - Microvascular dysfunction: a link between pre-eclampsia and maternal coronary
      heart disease.
AB  - Epidemiological studies have recently demonstrated a relationship between pre
      eclampsia and coronary heart disease. Insulin resistance has been implicated as a
      common factor. We have demonstrated, for the first time, using laser Doppler
      imaging in vivo, impaired microvascular function in women 15-25 years following a
      pregnancy complicated by pre-eclampsia. Thus, microvascular dysfunction, which is
      associated with insulin resistance, may be a predisposing vascular mechanism for
      both coronary heart disease and pre-eclampsia. Pregnancies complicated by pre
      eclampsia may identify women at risk of vascular disease in later life and may
      provide the opportunity for lifestyle and risk factor modification to alter
      maternal vascular disease risk.

PMID- 14592592
TI  - Actinomyces on a papanicolaou smear following a radical trachelectomy.

PMID- 14592591
TI  - 'Pure' pre-eclampsia before 20 weeks of gestation: a unique entity.

PMID- 14592595
TI  - A European CDC.

PMID- 14592593
TI  - Defective embryogenesis with angiotensin II receptor antagonists in pregnancy.

PMID- 14592596
TI  - Transmission of HIV-2.

PMID- 14592597
TI  - Lyme borreliosis.

PMID- 14592598
TI  - Epidemiology of Candida species infections in critically ill non-immunosuppressed
      patients.
AB  - A substantial proportion of patients become colonised with Candida spp during
      hospital stay, but only few subsequently develop severe infection. Clinical signs
      of severe infection manifest early but lack specificity until late in the course
      of the disease, thus representing a particular challenge for diagnosis. Mostly
      nosocomial, invasive candidiasis occurs in only 1-8% of patients admitted to
      hospitals, but in around 10% of patients housed in intensive care units where it
      can represent up to 15% of all nosocomial infections. We review the epidemiology
      of invasive candidiasis in non-immunocompromised, critically ill patients with
      special emphasis on disease trends over time, pathophysiology, diagnostic
      approach, risk factors, and impact. Recent epidemiological data suggesting that
      the emergence of non-albicans candida strains with reduced susceptibility to
      azoles, previously linked to the use of new antifungals for empiric and
      prophylactic therapy in immunocompromised patients, may not have occurred in the
      critically ill. Management of invasive candidiasis in these patients will be
      addressed in the December issue of The Lancet Infectious Diseases.

PMID- 14592599
TI  - Treatment of opportunistic mycoses: how long is long enough?
AB  - For most opportunistic mycoses no optimum duration of antifungal therapy has been
      defined. Although a long course of therapy is prudent, especially for mycelial
      fungal infections, excessively and unnecessarily extended courses of treatment
      incur a risk of toxicity and the expense of the therapeutic regimen. On the basis
      of existing reports on the pathogenesis and the effect of duration of therapy and
      other variables on outcome and response rate in fungal infections, this review
      proposes guidelines that may facilitate a rational approach to decision-making
      about the duration of antifungal therapy.

PMID- 14592600
TI  - Avascular necrosis of femoral heads in a man with HIV infection.

PMID- 14592601
TI  - Q fever: a biological weapon in your backyard.
AB  - Coxiella burnetii, which causes Q fever, is a highly infectious agent that is
      widespread among livestock around the world. Although the culture process for
      coxiella is laborious, large amounts of infectious material can be produced. If
      used as an aerosolised biological weapon, coxiella may not cause high mortality,
      but could provoke acute disabling disease. In its late course, Q fever can be
      complicated by fatal (eg, endocarditis) or debilitating (eg, chronic fatigue
      syndrome) disorders. The diagnosis of Q fever might be delayed because of non
      specific and protean presentations. Effective antibiotic treatment is available
      for the acute form of disease but not for the chronic complications. Vaccination
      and chemoprophylaxis in selected individuals may be used in the event of
      bioterrorism.

PMID- 14592602
TI  - Pott's puffy tumour: a rare clinical entity.

PMID- 14592603
TI  - Effects of chloroquine on viral infections: an old drug against today's diseases?
AB  - Chloroquine is a 9-aminoquinoline known since 1934. Apart from its well-known
      antimalarial effects, the drug has interesting biochemical properties that might
      be applied against some viral infections. Chloroquine exerts direct antiviral
      effects, inhibiting pH-dependent steps of the replication of several viruses
      including members of the flaviviruses, retroviruses, and coronaviruses. Its best
      studied effects are those against HIV replication, which are being tested in
      clinical trials. Moreover, chloroquine has immunomodulatory effects, suppressing
      the production/release of tumour necrosis factor alpha and interleukin 6, which
      mediate the inflammatory complications of several viral diseases. We review the
      available information on the effects of chloroquine on viral infections, raising
      the question of whether this old drug may experience a revival in the clinical
      management of viral diseases such as AIDS and severe acute respiratory syndrome,
      which afflict mankind in the era of globalisation.

PMID- 14592604
TI  - The possibility of eliminating blinding trachoma.
AB  - Global elimination of blinding trachoma, the world's leading preventable cause of
      blindness, now seems possible. The disease, which persists most severely in the
      poorest parts of Africa and Asia, is already eliminated in North America and
      Europe. On a scientific basis, the case for elimination was outlined at a WHO
      global scientific meeting in 1996. To facilitate action, WHO founded the Alliance
      for Global Elimination of Trachoma by 2020 (GET 2020) in 1997. In 1998 a World
      Health Assembly resolution called for member states to take steps to eliminate
      blinding trachoma by 2020 using the WHO recommended SAFE strategy (surgery of
      late stage disease, antibiotics for acute infection, and improved facial hygiene
      and environmental change-ie, improved access to water and sanitation). These
      developments contributed to the decision by Pfizer Inc to donate azithromycin in
      support of national programmes implementing SAFE and, with the Edna McConnell
      Clark Foundation, to found the International Trachoma Initiative as a charity
      dedicated to the elimination of blinding trachoma by 2020. Reports of the early
      programme scope and impact are encouraging. In ten national programmes currently
      underway (constituting about 50% of the global burden) more than 55,000 lid
      surgeries have halted further corneal damage and prevented blindness, and more
      than 6 million treatments with azithromycin have been given with reductions in
      acute infections of around 50% in children. Morocco, one of the first countries
      to implement SAFE with azithromycin, has achieved remarkable results and expects
      to eliminate blinding trachoma by 2005. If political will and public-health
      support can be mobilised, the goal of eliminating this cause of blindness can
      become a reality by 2020.

PMID- 14592606
TI  - Robert E W Hancock--boosting innate immunity to combat infection: interview by
      Marilynn Larkin.

PMID- 14592609
TI  - Wish you weren't here.

PMID- 14592610
TI  - Stereochemistry in clinical medicine: a neurological perspective.
AB  - Stereoisomers are compounds that have identical sets of atoms configured in the
      same positions but are arranged differently spatially. Approximately 25% of
      contemporary drugs are marketed and used as racemates (i.e., as equimolar
      mixtures of stereoisomers). This may have major clinical implications, as
      stereoisomers may possess qualitative and/or quantitative differences in
      pharmacological effects, plasma protein and tissue binding, metabolic and renal
      clearance. There are many examples of racemic drugs manufactured and used as
      single stereoisomers in the field of neurology including the anti-Parkinsonian
      drugs levodopa, selegiline, apomorphine and entacapone, the antiepileptic drugs
      tiagabine and levetiracetam, the secondary stroke prevention agent clopidogrel
      and the acetylcholinesterase inhibitor rivastigmine. The role of drug
      stereochemistry in the re-evaluation of established drugs and the production of
      new agents is becoming increasingly important as pharmaceutical companies
      endeavour to show proof of "no penalty" for the introduction of a racemic new
      drug over one or other of its single stereoisomers.

PMID- 14592611
TI  - Status epilepticus, the grim reaper of the mental health system in early
      Victoria.
AB  - In an era when patients with refractory epilepsy were managed in mental asylums
      in the colonial days of Victoria, Australia, the opinion of the administration
      was that such patients seemed to have a benign prognosis. However the decision to
      collect all female epileptics in the colony and manage them in the Ballarat
      Mental Hospital, effected in 1901, allowed scrutiny of the progress of a cohort
      of 96 patients over the first seventeen years of the twentieth century, thereby
      revealing that under asylum conditions no less than a third of their number died
      as the result of status epilepticus. The results of this survey and the reasons
      for such an outcome are discussed.

PMID- 14592613
TI  - A prospective study of predictors of prolonged hospital stay and disability after
      stroke.
AB  - This study examined predictors of prolonged hospitalisation (>30 days) and
      significant disability (modified Rankin Scale >2) in 257 patients with acute
      ischaemic stroke. These patients were assessed prospectively regarding stroke
      severity, comorbidities and complications in hospital. Multivariate logistic
      regression was used to select variables that best predicted prolonged hospital
      stay and significant disability on discharge. Four factors significantly
      predicted prolonged hospital stay: older age (>65); diabetes mellitus; in
      hospital infection; and significant disability on discharge. Significant
      disability on discharge was in turn associated with diabetes, infection,
      premorbid disability, stroke in progression and atrial fibrillation. Diabetes and
      in-hospital infection, together with other factors, can significantly predict
      prolonged hospital stay and disability in stroke patients. These two potentially
      modifiable factors are possible targets for interventions to reduce the burden of
      illness and healthcare costs of stroke.

PMID- 14592612
TI  - Evaluation of the use of BioGlue in neurosurgical procedures.
AB  - OBJECTIVE: Post-operative cerebrospinal fluid (CSF) fistula following
      neurosurgery is associated with increased morbidity and mortality. This
      prospective study evaluates the efficacy of a new bioadhesive--BioGlue, as a
      dural sealant in preventing CSF fistula. The complications associated with its
      use are investigated and the literature regarding dural closure reviewed.
      METHODS: BioGlue was applied to the dura mater as a sealant in 210 patients
      undergoing 216 neurosurgical procedures over a period of 22 months at the Royal
      Melbourne Hospital. It was used where watertight closure of the dura mater could
      not be ensured by primary suture alone and for reconstruction of the sellar floor
      following transsphenoidal adenohypophysectomy. It was used in 114 supratentorial
      (52.7%), 53 infratentorial (24.5%) craniotomies, 41 (18.9%) transsphenoidal
      adenohypophysectomies and 8 spinal (3.7%) procedures. The incidence of CSF
      fistula as a complication of surgery with intradural exposure was analysed.
      RESULTS: The incidence of CSF fistula post-operatively was significantly low. Two
      patients (0.93%), both having undergone posterior fossa craniotomy--for
      evacuation of a cerebellar haematoma and redo excision of a metastasis
      respectively and both complicated by hydrocephalus, developed CSF fistula. There
      were no complications associated with the use of BioGlue. CONCLUSION: BioGlue
      reduced the incidence of complications associated with neurosurgery. It is an
      effective adjunct in dural closure to prevent CSF fistula with enhanced bonding
      properties and is simple to use. In this study there were no complications
      associated with its use.

PMID- 14592614
TI  - Hemispheric asymmetry and temporal profiles of cerebral pressure autoregulation
      in head injury.
AB  - A moving correlation index (Mx-ABP) between arterial blood pressure (ABP) and
      mean middle cerebral artery blood flow velocity (CBFV) can be used to monitor
      dynamic cerebrovascular autoregulation (CA) after traumatic brain injury (TBI).
      In this study we examined hemispheric CA asymmetry and temporal CA profiles,
      their relationship with ABP and CBFV, and their prognostic relevance. Mx-ABP was
      calculated for each hemisphere in 25 TBI patients second-daily for as long as
      they were receiving sedation and analgesia. Forty-nine recordings were obtained,
      between one and six per patient. Four time periods were defined: immediate-
      postinjury days (PID) 0 and 1; early--PID 2 and 3; intermediate--PID 4 and 5, and
      late--PID 6 and later. GOS was estimated at discharge, GOS 4 and 5 were
      considered favorable (15 patients) and GOS 1-3 unfavorable outcome (10 patients).
      A Mx difference >0.2 was classified as hemispheric asymmetry (HA). HA was
      observed at least once in 12 of the 25 patients (48%) and in 18 of 49 recordings
      (37%). It was observed during all time periods: 35%, 43%, 25%, 43%, respectively,
      and was not related to outcome. There was no difference in mean CBFV or ABP
      between patients with and without HA. HA was not related to interhemispheric CBFV
      differences. A significant improvement in Mx was seen over time. Hemispheric CA
      asymmetry is common after traumatic brain injury. It does not bear significant
      clinical or predictive relevance, and it is unrelated to CBFV or ABP. CA is most
      profoundly disturbed during the immediate postinjury phase and improves gradually
      during the ICU course. Further studies are needed to investigate CA during post
      ICU recovery and rehabilitation.

PMID- 14592615
TI  - Rerupture of intracranial aneurysms during cerebral angiography.
AB  - Three cases of re-rupture of intracranial aneurysms during cerebral angiography
      (RIADCA) between June and September, 2001 are reported. All cases underwent
      emergency craniotomy and aneurysm clipping. The subarachnoid blood and the
      extravasating contrast medium were removed intraoperatively as completely as
      possible. There was no mortality in this series. The incidence, timing, sex, age,
      inducing factors, risk factors, prevention measures and prognosis are discussed
      and reviewed in conjunction with the literature.

PMID- 14592617
TI  - Chronic expanding intracerebral hematoma.
AB  - In order to study the clinical characteristics of chronic expanding intracerebral
      hematoma (CEICH), we analyzed retrospectively 21 patients with CEICH and reviewed
      the literature with regard to clinical manifestations, medical imaging features,
      surgical findings, pathological examinations, diagnoses, treatments and
      prognoses, etc. All patients recovered well and did not recur 1-2 months after
      operation, except one, who died of contralateral intracerebral hemorrhage three
      months later. Patients were followed-up by computerized tomographic (CT)
      scanning. MRI was useful for the preoperative diagnosis.

PMID- 14592616
TI  - Significant elevation of urinary trypsin inhibitor in patients with brain
      contusion--a preliminary report.
AB  - Urinary trypsin inhibitor (UTI) is a protease inhibitor, which is produced in the
      liver. The correlation between UTI level and head injury has not been evaluated.
      This study was designed to investigate UTI levels in patients with severe head
      injury. We measured UTI in the urine of patients with brain contusion. UTI was
      significantly higher in those patients compared to the control group. The results
      suggest that UTI may be useful for assessing the severity of head injury and also
      as a treatment marker in patients with brain contusion.

PMID- 14592618
TI  - Cavernous hemangioma. Reversible posterior leukoencephalopathy syndrome.

PMID- 14592619
TI  - Changes of mGluR4 and the effects of its specific agonist L-AP4 in a rodent model
      of diffuse brain injury.
AB  - OBJECTIVE: Excessive release of glutamate from nerve terminals following diffuse
      brain injury (DBI) is thought to contribute to neuronal calcium overload leading
      to calcium-mediated cell damage. Metabotropic glutamate receptor subtype 4
      (mGluR4) is regarded as one of the neuroprotective receptors in mammalian brains.
      Therefore, the mGluR4 specific agonists might exert neuroprotective effects after
      DBI. The focus of this study is to examine the changes of expression of mGluR4
      after DBI and the role of its specific agonist L-AP4 in vivo. METHODS: One
      hundred and sixty-one male SD rats were randomized into two groups. Group A
      included normal control, sham-operated control and DBI group. DBI was produced by
      Marmarou's diffuse head injury model. The mRNA expression of mGluR4 was detected
      by hybridization in situ. Group B included DBI alone, DBI treated with normal
      saline and DBI treated with L-AP4. All DBI rats were trained in a series of
      performance tests, following which they were subjected to DBI. At 1 and 12 h,
      animals were injected intracerebroventricularly with L-AP4 (100 mM, 10 microl) or
      normal saline, respectively. The rats were tested for motor and cognitive
      performance at 1, 3, 7, 14 days post-injury and the damaged neurons were
      detected. RESULTS: There was no significant difference between the normal control
      group and sham-operated group in the expression of mGluR4 (P>0.05). The animals
      exposed to DBI showed a significant increased expression of mRNA of mGluR4
      compared with that of the sham-operated animals 1 h after injuries (P<0.05). At 6
      h, the evolution of neuronal expression of mGluR4 in the trauma alone group was
      relatively static. Compared with saline-treated control animals, rats treated
      with L-AP4 showed decreased number of damaged neurons and a better motor and
      cognitive performance. CONCLUSIONS: The increased expression of mGluR4 is an
      important process in the pathophysiological of DBI and its specific agonist L-AP4
      can provide a remarkable neuroprotection against DBI not only at the
      histopathological level but also in the motor and cognitive performance.

PMID- 14592620
TI  - Ruptured distal anterior choroidal artery aneurysm presenting with right
      intracerebral haematoma: clipping aided by subpial uncal resection.
AB  - This report describes a rare case of a distal right anterior choroidal artery
      aneurysm which developed a right intracerebral haematoma and intraventricular
      haemorrhage and was treated by surgical exploration and clipping with the aid of
      a limited subpial resection of the uncus and ambient gyrus. The technique of
      limited subpial uncal resection allows the surgeon to follow the anterior
      choroidal artery without much difficulty, achieves proximal control early and
      aids in the eventual clipping procedure.

PMID- 14592621
TI  - Isolated spinal cord lipoma.
AB  - A case of isolated intradural spinal cord lipoma is presented. Most isolated
      spinal cord lipomas are intradural extramedullary, and the most common location
      is subpial. True intramedullary lipomas are very rare. Patient history is usually
      of months to years of local back pain, with recent escalation of pain and
      development of neurological symptoms. MRI examination shows a well circumscribed
      lesion of high signal on both T1 and T2 weighted images, and suppression on fat
      saturation sequence. Subtotal resection is the surgical aim. This improves pain
      but neurological symptoms rarely improve, usually are unchanged, and occasionally
      are worse.

PMID- 14592623
TI  - Non-Hodgkin's lymphoma involving the cauda equina and ocular cranial nerves: case
      reports and literature review.
AB  - Although rare, direct infiltration of the cauda equina by non-Hodgkin's lymphoma
      (NHL) must be considered as a potential cause of subacute onset paraplegia. We
      present two cases of lymphomatous involvement of the cauda equina presenting with
      subacute paraplegia, each associated with a palsy of an oculomotor nerve. We
      highlight the need to use gadolinium-enhanced magnetic resonance imaging (MRI)
      when investigating potential cauda equina lesions, since it is crucial in
      detecting and outlining the extent of disease. Differential diagnoses and
      treatment options for NHL involving the cauda equina are also discussed.

PMID- 14592622
TI  - A marked decrease in bispectral index with elevation of suppression ratio by
      cervical haematoma reducing cerebral perfusion pressure.
AB  - A 77-year-old man with a ruptured abdominal aortic aneurysm undergoing
      aneurysmectomy were anaesthetised with ketamine under bispectral index (BIS)
      monitoring, which is a clinical EEG monitor for measurement of depth of
      anaesthesia/sedation. First marked BIS reduction with elevation of suppression
      ratio (SR) was observed following severe hypotension by deflation of the aortic
      occlusion balloon. The re-inflation and rapid blood transfusion improved
      haemodyanamics and BIS and SR. At second marked BIS reduction with SR elevation,
      a heavy cervical swelling due to a massive subcutaneous haematoma around the
      previously mis-punctured right carotid artery extending throughout the whole neck
      was observed without hypotension. Cervical relief incision improved the BIS and
      SR. The present case suggests that BIS monitor may be a simple and convenient
      monitor for cerebral ischaemia detection.

PMID- 14592624
TI  - Subclavian steal syndrome with an unusual presentation.
AB  - Steal syndrome has been known since 1960 in the medical literature. It is the
      pathological process in which blood flows in reverse direction and if vessels
      supplying the intracranial structures are involved, a variety of neurological
      symptoms may develop. In this paper, we report a case with left subclavian steal
      syndrome that presented solely by paroxysmal numbness on the right side of the
      lip and tongue and discuss the clinical importance from the neurological point of
      view.

PMID- 14592625
TI  - Impaired hypothalamic endocrine function in neuroacanthocytosis.
AB  - Two sisters aged 28 and 26, suffering from neuroacanthocytosis (NA), had
      hypothyroidism and showed a flat growth hormone (GH) response to the insulin
      tolerance test. GH-releasing hormone (GHRH) administration resulted in a normal
      GH response in the older sister and a partial GH response in the younger sister.
      A pathological process--attributable to NA--can be suggested, leading to impaired
      hypothalamic function, but sparing the pituitary.

PMID- 14592626
TI  - Brain metastases from urachal carcinoma.
AB  - We present a case of brain metastases of the urachal carcinoma, which is
      extremely rare and malignant. Contrast-enhanced MRI was employed to detect them.
      A large mass was removed surgically and 4 other small metastases were treated by
      gamma knife radiosurgery. Six weeks after radiosurgery, the 4 lesions had
      disappeared on MRI. We emphasise the importance of early diagnosis using MRI and
      treatment by radiosurgery for this rare condition.

PMID- 14592627
TI  - 'Ecstasy'-induced subarachnoid haemorrhage: an under-reported neurological
      complication?
AB  - In the face of escalating recreational use of 'Ecstasy' (3,4
      methylenedioxymethamphetamine, MDMA), physicians need to be aware of its possible
      adverse effects. We report two young patients who suffered subarachnoid
      haemorrhage following ingestion of 'Ecstasy' tablets. Angiographic studies
      demonstrated features consistent with vasculitis in both cases. Recognition of
      this association is important and highlights the significance of eliciting a
      careful drug history, particularly in cases of 'angiogram negative' subarachnoid
      haemorrhage.

PMID- 14592629
TI  - Solitary extra-axial posterior fossa abscess due to neurobrucellosis.
AB  - Neurobrucellosis is a rare manifestation of systemic brucellosis. The incidence
      of nervous system involvement in chronic Brucellosis is approximately 5%. In this
      case report a solitary, extra-axial posterior fossa abscess due to
      neurobrucellosis is presented. The clinical manifestations, diagnosis, and
      treatment of this unusual condition are discussed.

PMID- 14592628
TI  - Management of massive calcified transdural thoracic disk herniation.
AB  - Thoracic disk herniation is a not uncommon pathology faced by the spinal surgeon.
      The management of massive intradural thoracic disk herniation with ventral cord
      compression is problematic both in terms of obtaining adequate decompression and
      ensuring no subsequent leakage of cerebrospinal fluid. A 54-year-old woman
      presented with a 10 year history of back pain and left leg pain. Over the past 6
      months she experienced a progressive spastic paraparesis in both legs with recent
      urinary incontinence. A left anterolateral thoracotomy for excision of T8/9
      thoracic disk protrusion was affected. A transdural decompression was performed
      with resection of the calcified dura and performance of a Gore-Tex duraplasty and
      pleuroplasty. A free muscle graft was placed in the intervening space and the
      chest drains were placed on non-suction. A spinal drain was maintained for 5
      days. She made an excellent neurological recovery. Avoidance of cerebrospinal
      leakage is paramount when performing transthoracic approaches as negative
      intrapleural pressure can lead to persistence of leakage. This report documents a
      safe and reliable way to deal with massive intradural thoracic disk rupture with
      avoidance of subsequent spinal fluid leak.

PMID- 14592631
TI  - Museum of neurosurgical instruments: catalogue with historical commentaries.

PMID- 14592630
TI  - Lipomeningioma: case report and review of the literature.
AB  - We present a case of histologically confirmed lipomeningioma, the first to our
      knowledge reported in Australia. A 61-year-old man presented with seizures and
      confusion, and was found to have a non-enhancing left extra axial temporo
      parietal lesion on CT and MRI scan. On MRI, the mass lesion showed hyper
      intensity on the T1 weighted images, hypo-intensity on fat suppressed T2 weighted
      images and no enhancement with intravenous gadolinium, indicating a mass
      consisting predominantly of fatty tissue. A subsequent CT also showed the mass
      lesion to be hypodense with Hounsfield units indicating fatty tissue. A durally
      based tumour with high fat content macroscopically was excised at craniotomy
      under ultrasound guidance. Post-operative recovery was uneventful. Histology
      demonstrated a meningioma with high lipid content in the form of mature
      adipocytes and without atypical features. While not exceedingly rare, fewer than
      30 cases of lipomeningioma, lipomatous meningioma, or lipidised meningioma have
      been reported in the world literature.

PMID- 14592632
TI  - Percutaneous endoscopic gastrostomy in amyotrophic lateral sclerosis: a word of
      caution.

PMID- 14592635
TI  - The impact of mood disorders in neurological diseases: should neurologists be
      concerned?
AB  - Depression is one of the most frequent comorbid psychiatric disorders identified
      in patients with neurological disorders. The prevalence rates range between 20
      and 50% of patients with stroke, epilepsy, multiple sclerosis, and Parkinson's
      disease. Despite these relatively high prevalence rates, depression remains
      underrecognized and undertreated in these patients. And yet, depression accounts
      for poor quality-of-life ratings and has a negative impact on the recovery from
      neurological symptoms. In this article, we review the epidemiological and
      clinical characteristics of mood disorders in patients with multiple sclerosis,
      Parkinson's disease, stroke, and epilepsy, and focus on the impact mood disorders
      have on the quality of life of these patients and on their recovery from their
      neurological deficits.

PMID- 14592636
TI  - Common pathogenic mechanisms between depression and epilepsy: an experimental
      perspective.
AB  - Affective disorders and the epilepsies appear to share partially similar
      pathogenic mechanisms. Predisposition to both disorders is determined genetically
      and experientially. A component of the shared predisposition appears to arise
      from noradrenergic and serotonergic deficits. Shared GABAergic deficits coupled
      with CRHergic and glutamatergic excesses may trigger and maintain seizures as
      well as dysfunctional affective episodes, albeit via dissimilar neuronal
      interplay.

PMID- 14592637
TI  - Mechanisms of depression in epilepsy from a clinical perspective.
AB  - The epilepsies are a complex group of disorders commonly associated with brain
      dysfunction, social isolation, and vocational difficulty. Each of these factors
      may contribute to increased prevalence of depressive disorders in epilepsy, but
      the specific mechanisms are not completely understood. The brain regions commonly
      involved in various types of epilepsies, such as the hippocampus and amygdala in
      temporal lobe epilepsy and subcortical nuclei in idiopathic generalized
      epilepsies, are important components of current models of depression. Increased
      understanding of mechanisms of depression in epilepsy is not only crucial for
      improving care of many persons with seizures, but may also yield useful
      information about principal mechanisms underlying both depression and
      epileptogenesis.

PMID- 14592638
TI  - Rates and risk factors for suicide, suicidal ideation, and suicide attempts in
      chronic epilepsy.
AB  - Studies of causes of death among people with epilepsy suggest that the lifetime
      prevalence rate of suicide is elevated. Although not all of the studies have
      reported an increased risk for suicide, the collective data yield an average rate
      of approximately 12% among people with epilepsy, compared with 1.1-1.2% in the
      general population. The increased risk for suicide appears to affect children and
      adolescents as well as adults. Rates of suicide attempts have also been reported
      to be elevated among people with epilepsy. A suicide attempt is a significant
      risk factor for completed suicide. Certain psychiatric disorders, including
      primary mood disorders, also increase the risk for suicide. Among people with
      epilepsy, psychiatric comorbidity is common, and rates of mood disorders,
      particularly major depression, have consistently been reported to be elevated.
      Other potential risk factors are family issues, physical health, personality,
      life stress, previous suicidal behavior, and access to firearms. Assessing
      severity of risk helps to determine the appropriate level of intervention. The
      suicidality module of the Mini-International Neuropsychiatric Interview is a
      practical tool to help quantify current suicide risk.

PMID- 14592640
TI  - Treatment of depression in patients with epilepsy: problems, pitfalls, and some
      solutions.
AB  - Many people with epilepsy suffer from comorbid depression. Despite this, there
      have been few studies addressing the treatment of depression in this population,
      and the literature on psychiatric management techniques in patients with epilepsy
      is composed largely of opinions rather than evidence from randomized, controlled
      trials or other systematic investigations. Antidepressant drugs, including
      tricyclics and selective serotonin reuptake inhibitors, can be used to treat
      patients with epilepsy and comorbid depression. Nonpharmacological treatment
      options include vagus nerve stimulation, transcranial magnetic stimulation, and
      psychological therapies including cognitive-behavioral therapy, individual or
      group psychotherapy, patient support groups, family therapy, and counseling.
      Another important area that remains largely uninvestigated is psychiatric
      research in patients with epilepsy in non-Western cultures (with the exception of
      Japan). Factors such as problems with access to and acceptability of therapies in
      many developing nations have further implications for the treatment of
      psychiatric disorders in epilepsy.

PMID- 14592639
TI  - Depression in children and adolescents with epilepsy.
AB  - Depression in children and adolescents with epilepsy is a common but often
      unrecognized disorder. Both epilepsy and depression are characterized by a
      chronic course and poor long-term psychosocial outcome. The risk of suicide is
      even greater in depressed youth with epilepsy than in the general youth
      population. Educating parents about mood disorders may allow them to be more
      receptive to psychiatric treatment for their child or themselves. Epidemiological
      and clinical data on depression in children/adolescents with epilepsy are
      presented. Seizure-related and general risk factors for the development of
      depression in youth with epilepsy are reviewed. General guidelines for diagnosis
      and treatment of depression in children and adolescents are discussed. The early
      identification and treatment of childhood-onset depression is an important
      clinical task for all pediatric specialists. Safe and effective multimodal
      treatment approaches are available.

PMID- 14592642
TI  - Comments on the 2001 WHO proposal for the classification of haematopoietic
      neoplasms.
AB  - In the preface, the World Health Organization (WHO) classification vows to offer
      pathologists, oncologists and geneticists worldwide a system of classification
      for human neoplasms based on histopathological and genetic features.
      Standardization of nomenclature and agreed-upon criteria for definition of the
      various types of cancer are felt to be a prerequisite for progress in clinical
      oncology, multicentre therapy trials and comparative studies in different
      countries. In fact, the WHO effort represents the first worldwide comprehensive
      consensus classification of the haematological malignancies. Consensus was
      reached among a subgroup of investigators, carefully selected for their
      experience and contributions to existing classifications. In the present climate
      of daily new discoveries that yield a constant stream of fascinating insights
      into the biology of leukaemias and lymphomas and, above all, resulting in an
      explosion of potential therapeutic targets, the WHO system has taken the stand of
      compiling established classification approaches and providing order to known
      facts. This furnishes an essential skeleton upon which to build in the future.
      The WHO committee decided that sorting neoplasms according to prognosis was
      neither practical nor necessary and could be misleading. While justifiable at the
      present time, it is important to realize that the classifications of the
      haematological malignancies are a moving target and that the trend is to move
      away from currently accepted gold standards, such as morphological evaluations,
      in favour of genetic characterizations, especially those with therapeutic
      relevance. The goal of this chapter is to fill in some gaps that, as per the
      author's opinion, exist in the WHO classification, predominantly, where it
      concerns the role of immunophenotyping as a complementary discipline for
      genotyping through its potential to generate surrogate marker profiles for
      molecular lesions. By introducing some state-of-the-art classification
      modalities, some of which are still awaiting confirmation, this chapter also aims
      to spark excitement and provide a glimpse at the future.

PMID- 14592643
TI  - Classification systems for acute and chronic leukaemias.
AB  - Modern classification systems for acute and chronic leukaemias are based on
      cytomorphology, cytochemistry, immunophenotyping, immunogenetics and molecular
      cytogenetics. Morphology forms the initial diagnosis of leukaemia, but generally
      is not sufficient to identify biologically and clinically relevant subsets within
      the main categories of leukaemia. Immunophenotyping precisely defines the lineage
      and stage of differentiation of malignantly transformed haematopoietic cells.
      This is usually sufficient for precise classification of mature lymphoid
      malignancies, although immunogenetic and (molecular) cytogenetic studies might be
      helpful to confirm the diagnosis of disseminated non-Hodgkin's lymphomas.
      However, certain categories of disease that are clearly defined by cytomorphology
      and immunophenotyping, particularly acute leukaemias, are still heterogeneous,
      mainly owing to different underlying leukaemogenic events. Immunophenotyping can
      reveal subgroups highly suggestive of certain chromosome aberrations but reliable
      identification of such aberrations requires cytogenetic or molecular studies.
      Such combined diagnostic information forms the basis of current WHO
      classification of tumours of haematopoietic and lymphoid tissues. This will be
      complemented in the near future with novel criteria revealed by microarray gene
      expression profiling. This chapter summarizes and comments on the currently used
      immunophenotypic classification systems of acute and chronic leukaemias and on
      the added value of molecular diagnostics.

PMID- 14592644
TI  - Flow cytometry in lymphoma diagnosis and prognosis: useful?
AB  - Flow cytometry has become an important tool in the diagnosis of mature lymphoid
      neoplasms and the determination of prognosis in selected cases. The advantages of
      flow cytometry are based largely on its ability to analyse, rapidly and
      simultaneously, multiple cell properties in a quantitative manner. Flow
      cytometric immunophenotyping is useful in diagnosing lymphoma under the WHO
      classification system, where lymphoid neoplasms are separated into distinct
      clinical entities based upon morphology, immunophenotype, genetic abnormalities
      and clinical features. Flow cytometry can quantify the expression of proteins
      associated with a good or poor prognosis, detect multidrug resistance, and
      measure cell proliferation, making it useful in measuring prognostic indicators
      in lymphoid neoplasia. The unique attributes of flow cytometry therefore make it
      a valuable technique in the diagnosis and classification of lymphomas as well as
      the assessment of prognostic markers in lymphoma patients.

PMID- 14592645
TI  - Minimal residual disease monitoring by flow cytometry.
AB  - In patients with acute leukaemia, studies of minimal residual disease (MRD)
      provide powerful and independent prognostic information. Multiparameter flow
      cytometry is a widely applicable and reliable approach for monitoring MRD. Using
      triple or quadruple marker combinations, aberrant or uncommon phenotypic profiles
      can be identified in about 80% of patients with acute myeloid leukaemia (AML) and
      95% of patients with acute lymphoblastic leukaemia (ALL). These profiles can
      reveal leukaemic cells even when these are not evident by morphological analysis.
      Thus, one leukaemic cell among 1000-10000 normal bone marrow or peripheral blood
      cells can be routinely detected. In this chapter we discuss technical aspects of
      MRD detection by flow cytometry and summarize results of correlative studies
      between MRD, clinical and biological features of leukaemia and treatment outcome.
      Current knowledge indicates that MRD studies using well-tested methodologies are
      clinically useful and should be incorporated into the clinical management of
      patients with acute leukaemia.

PMID- 14592646
TI  - The prognostic significance of antigen expression in leukaemia.
AB  - Numerous immunophenotypic features have been examined for their potential
      prognostic significance in predicting treatment outcome in leukaemias. These
      include immunophenotypic subgroups of acute lymphoblastic leukaemia (ALL) and
      immature acute myeloid leukaemia, expression of individual surface antigens or
      combined immunophenotypic features, and more recently, molecules mediating the
      multidrug resistance phenotype or being involved in the regulation of drug
      induced apoptosis. Most previous studies investigating the prognostic
      significance of antigen expression in leukaemia have not used the information
      provided by multiparameter flow cytometry and have chosen rather arbitrary cut
      off points for marker positivity. Moreover, given significant associations
      between immunophenotypic features and genetic abnormalities in leukaemic cells,
      immunophenotyping as an independent predictor of treatment outcome has been
      questioned. Thus, except for lineage assignment of leukaemic blasts and
      definition of maturational status in ALL, information provided by
      immunophenotyping is currently not applied to risk-classification systems or used
      for planning patient treatment in leukaemia. We review some of the recent
      findings regarding the prognostic impact of distinct immunophenotypic features in
      acute leukaemias and myelodysplastic syndrome.

PMID- 14592647
TI  - Immunophenotyping as a guide for targeted therapy.
AB  - Immunophenotyping of acute and chronic leukaemias has revealed many lineage- and
      differentiation-specific antigens. It has now become possible to classify
      leukaemias according to their unique antigenic expression pattern. Among many
      lineage- and differentiation-specific antigens, disease-specific antigens are
      increasingly recognized because of their specific prognostic or therapeutic
      relevance. Expression of the multidrug resistance proteins of the ABC transporter
      family is associated with a poor response to treatment and a grave clinical
      prognosis. Recently, attempts to reverse refractory disease by using P
      glycoprotein inhibitors have been performed in acute myeloid leukaemia, so far
      without evidence of clinical benefit. Other new leads to use antigen expression
      as a way of designing tumour-specific therapy have resulted in imatinib and Flt3
      inhibitors which target tyrosine kinases in the leukaemic cell. Clinical trials
      are underway to investigate the effect of these new agents. The development of an
      antibody-calicheamycin complex directed against the myeloid-specific antigen CD33
      has shown clinical activity in patients with relapsed acute myeloid leukaemia.
      The further development of these approaches is discussed.

PMID- 14592648
TI  - Gene expression profiling: will it complement or replace immunophenotyping?
AB  - Gene expression profiling using DNA microarrays represents a major advance in the
      diagnosis of haematological malignancies; it enables the analysis of RNA
      expression by clonal populations of leukaemia and lymphoma cells on a genome-wide
      scale. Currently, flow cytometric analysis of differentiation-linked surface
      antigens expressed by malignant cells is essential for the accurate diagnosis and
      optimal therapeutic planning for patients with leukaemias and lymphomas. Given
      the astonishing pace of research in microarray technology, a key question for the
      haematopathologist is: will gene expression profiling using DNA microarrays
      replace immunophenotyping, or will these two technologies evolve together as
      complementary approaches to improve diagnosis and therapy? In this chapter, we
      review the technical advantages and pitfalls of each of these two approaches and
      provide an assessment of their differences and potentially synergistic
      applications.

PMID- 14592649
TI  - Diagnostic value of detecting fusion proteins derived from chromosome
      translocations in acute leukaemia.
AB  - Clonal chromosomal abnormalities such as balanced translocations are
      characteristic features of several human leukaemias and have long been detected
      by conventional cytogenetics on banded metaphases. The advent of molecular
      biology techniques, advanced karyotyping and immunohistochemistry methods has not
      only allowed identification of gene involvement at altered chromosome sites and
      better knowledge of leukaemia pathogenesis, but also contributed important
      improvements in diagnosis of these heterogeneous diseases. Such novel diagnostic
      strategies are nowadays being increasingly used to improve leukaemia
      classification, and in several instances, they help to establish the most
      appropriate therapeutic strategy in individual patients. Moreover, at least two
      leukaemia-associated fusion proteins derived from chromosome translocation are
      specifically targeted by therapeutic approaches which result in significantly
      increased anti-leukaemia efficacy and reduced toxicity. In this chapter, we
      highlight the importance of identifying these genetic lesions at diagnosis in
      acute leukaemia. Further, we discuss briefly the clinical utility of detecting
      these alterations for prognostic assessment and evaluation of response to
      treatment.

PMID- 14592650
TI  - How to optimize multiparameter flow cytometry for leukaemia/lymphoma diagnosis.
AB  - Multiparameter flow cytometry can allow for accurate lineage assignment of
      leukaemia cell populations in approximately 99% of cases, whereby the emphasis
      lies in the word 'can'. Despite the fact that the very few markers that are
      lineage-specific are localized inside the cell (e.g. myeloperoxidase,
      lactoferrin, cytoplasmic CD3, cytoplasmic CD22), several investigators still shy
      away from including these essential test elements in their routine panels. Of
      course, the staining of intracellular antigens requires the added effort of
      determining optimal conditions. Published suggestions often need to be revised,
      and cell lines must be used as positive and negative controls. The same holds
      true for other new and exciting applications of flow cytometry, such as the
      monitoring of minimal residual disease (MRD) or the establishment of
      physiological assays (e.g. measuring the activity of drug-efflux pumps). The
      beauty of-and unfortunately for some, the problem with-multiparameter flow
      cytometry is that although immunophenotyping by flow cytometry has become a
      routine approach to the diagnosis of haematological malignancies it is a
      discipline that is still in development. New antibodies are continually being
      introduced and new diagnostic and prognostically relevant subtypes are being
      published in almost every issue of the major scientific journals. It is therefore
      very important for the flow cytometrist not only to strive for optimal
      performance of all tests employed but also to keep up with new knowledge and to
      incorporate it into the interpretation of routine specimens. We owe it to our
      patients to diagnose their disease accurately and in accordance with accepted
      standards of interpretation so that the treating physicians can trust
      immunophenotyping results and act accordingly in the management of their
      patients.

PMID- 14592653
TI  - Abandonment.

PMID- 14592654
TI  - Tissue and organ engineering: can we build intestine and vital organs?

PMID- 14592655
TI  - Etiology, treatment, and outcome of esophageal ulcers: a 10-year experience in an
      urban emergency hospital.
AB  - Esophageal ulcers are a rare cause of upper gastrointestinal bleeding. This
      report describes the etiology, treatment, complications, and outcome of
      esophageal ulcers. An esophageal ulcer is defined as a discrete break in the
      esophageal mucosa with a clearly circumscribed margin; esophageal ulcers were
      seen in 88 patients from a total of 7,564 esophagogastroduodenoscopies done by
      one surgeon at an urban hospital from 1991 to 2001. All hospital reports were
      reviewed. The etiology of esophageal ulcers included the following:
      gastrointestinal reflux disease (GERD) (n=58, 65.9%), drug induced (n=20, 22.7%),
      candidal (n=3, 3.4%), caustic injury (n=2, 2.3%), and herpes simplex virus (HSV),
      human immunodeficiency virus (HIV), marginal ulcer, foreign body, and unknown
      etiology (n=1 of each, 1.1%). The mean size of GERD-induced esophageal ulcers and
      drug-induced esophageal ulcers was 2.78 and 2.92 cm, respectively; 80.3% of GERD
      induced esophageal ulcers and 13.8% of drug-induced esophageal ulcers were
      located in the lower thoracic esophagus. Morbidity (n=44, 50%) included
      hemorrhage (n=30, 34%), esophageal stricture (n=11, 12.5%), and esophageal
      perforation (n=3, 3.4%). Nonoperative therapy sufficed in 81 patients (92%).
      Three patients (3.4%) had a recurrence of esophageal ulcers. Fifteen patients
      (17.0%) required endoscopic intervention including esophageal dilatation for
      stricture in 11 patients and endoscopic hemostasis for esophageal bleeding in
      four patients. Surgery (n=7, 8.0%) was reserved for esophageal stricture and
      perforation. Two patients (2.3%) died from complications of esophageal ulcers:
      hemorrhage in one and perforation in one. Three patients died of their primary
      disease. GERD and drug ingestion are common causes of esophageal ulcers.
      Midesophageal ulcers have a greater tendency to hemorrhage compared with ulcers
      at the gastroesophageal junction; this may reflect the etiology. Strictures
      complicate GERD-induced esophageal ulcers but not drug-induced esophageal ulcers.
      Esophageal dilatation is an effective treatment for most strictures associated
      with esophageal ulcers. Esophageal ulcers rarely cause death.

PMID- 14592656
TI  - Electrical stimulation of the vagus nerve restores motility in an animal model of
      achalasia.
AB  - Esophageal peristalsis generally does not return to normal after surgical
      treatment of achalasia. Direct electrical stimulation of the vagus nerve is known
      to stimulate antegrade peristalsis in the normal esophagus; however, it is not
      known whether electrical stimulation will induce return of peristalsis once an
      achalasia-like disorder has been established. The objective of this study was to
      perform quantitive and qualitative measurements of motility during electrical
      stimulation of the vagal nerve in an animal model of achalasia. An already
      established and verified animal achalasia model using adult North American
      opossums (Didelphis virginiana) was used. Fifteen opossums were divided into
      three groups. Sham surgery was performed on three animals (group 1). In group 2
      (n=6) a loose Gore-Tex band (110% of the esophageal circumference) was placed
      around the gastroesophageal junction to prevent relaxation of the lower
      esophageal sphincter during swallowing. In group 3 (n=6) a relatively tighter
      band (90% of the esophageal circumference) was used to further elevate the lower
      esophageal sphincter pressure. At 6 weeks, after manometric and radiolologic
      confirmation of achalasia, electrical stimulation of the esophagus was performed
      before and after removal of the band using a graduated square-wave electrical
      stimulus. Changes in esophageal neural plexi were assessed histologically. Pre-
      and postoperative manometric data were compared using standard statistical
      techniques. No difference was observed in esophageal characteristics and motility
      after sham surgery in group 1. Animals in group 2 demonstrated a vigorous variety
      of achalasia (high-amplitude, simultaneous, repetitive contractions), moderate
      esophageal dilatation, and degeneration of 40% to 60% of intramuscular nerve
      plexi. Animals in group 3 developed amotile achalasia with typical low-amplitude
      simultaneous (mirror image) contractions, severely dilated ("bird beak")
      esophagus, and degeneration of 50% to 65% of nerve plexi. Vagal stimulation in
      group 2 demonstrated a significant increase in the amplitude of contractions
      (P<0.001) and return of peristaltic activity in 49% of swallows before band
      removal. After band removal, all of the contractions were peristaltic. In group 3
      vagal stimulation before and after removal of the band demonstrated a significant
      increase in amplitude of contractions (P<0.0001) but no return of propagative
      peristalsis before band removal, however, 44% of contractions were progressive in
      the smooth portion of the esophagus after removal of the band. Electrical
      stimulation of the vagus nerve improved the force of esophageal contractions
      irrespective of the severity of the disease; however, peristaltic activity
      completely returned to normal only in the vigorous (early) variety of achalasia.
      Removal of the functional esophageal outlet obstruction, as with a surgical
      myotomy, may be necessary to obtain significant peristalsis with vagal pacing in
      severe achalasia.

PMID- 14592657
TI  - Patterns of regional lymph node involvement in intrahepatic cholangiocarcinoma of
      the left lobe.
AB  - Lymph node involvement is an important prognostic factor in intrahepatic
      cholangiocarcinoma. Besides the nodes in the hepatoduodenal ligament, recent
      studies have suggested that the nodes around the cardiac portion of the stomach
      or along the gastric lesser curvature can be affected when the primary tumor is
      located in the left hepatic lobe. However, the distribution of metastatic nodes
      has not been well described in this disease. Thirteen patients with intrahepatic
      cholangiocarcinoma in the left hepatic lobe were enrolled in this study.
      Lymphatic mapping was performed by means of both histologic examination and
      reverse transcriptase-polymerase chain reaction assays. Nodal involvement around
      the cardiac portion of the stomach or along the lesser gastric curvature (left
      pathway) was found in 7 (54%) of 13 patients by histologic examination or reverse
      transcriptase-polymerase chain reaction, whereas positive nodes in the
      hepatoduodenal ligament (right pathway) were found in 6 (46%) of 13 patients. Two
      patients (15%) had positive nodes only in the left pathway. Therefore, for a more
      accurate clinical staging of intrahepatic cholangiocarcinoma in the hepatic left
      lobe, lymph nodes around the cardiac portion of the stomach and along the lesser
      gastric curvature should be examined in addition to nodes in the hepatoduodenal
      ligament.

PMID- 14592658
TI  - Diabetes and hyperlipidemia correlate with gallbladder contractility in leptin
      related murine obesity.
AB  - Obesity is associated with many comorbid conditions including diabetes,
      hyperlipidemia, and gallstones. However, the interaction among these modalities
      remains unclear. We recently demonstrated that both leptin-deficient and leptin
      resistant obese mice have impaired biliary motility. These obese mice also are
      diabetic and hyperlipidemic. Therefore, we tested the hypothesis that serum
      glucose, insulin, cholesterol, and triglyceride levels would correlate with
      gallbladder contractility. Thirty-four lean control, 10 lean heterozygous leptin
      deficient, 18 obese homozygous leptin-deficient, and 12 obese homozygous leptin
      resistant mice were fed a nonlithogenic chow diet while nine lean control and
      nine obese homozygous leptin-deficient mice were fed a high-cholesterol diet for
      4 weeks. In vitro gallbladder responses to cholecystokinin (CCK; 10(-8) mol/L),
      acetylcholine (ACh; 10(-5) mol/L), and neuropeptide Y (NPY; 10(-6) mol/L) were
      measured. Serum glucose, insulin, cholesterol, and triglyceride levels were
      measured from pooled serum from an additional 704 animals. Gallbladder responses
      were greatest for CCK, intermediate for ACh, and least for NPY. Serum glucose,
      insulin, cholesterol, and triglyceride levels and body weight all correlated
      similarly, negatively, and significantly (P<0.001) with gallbladder
      contractility. Hyperglycemia, insulin-resistance, hyperlipidemia, and body weight
      in obese mice with leptin dysfunction are associated with poor gallbladder
      contractility, which in turn may contribute to the association between obesity
      and gallstone formation.

PMID- 14592659
TI  - Butyrate inhibits pancreatic cancer invasion.
AB  - Pancreatic cancer is the most deadly gastrointestinal malignancy because of its
      propensity for local invasion and early metastasis. Integrin chains, in
      particular beta4, can promote invasion in other cancers. The effect of sodium
      butyrate (NaBT), which induces differentiation in transformed cells, on integrin
      expression is unknown. The purpose of this study was to determine patterns of
      integrin expression in pancreatic cancer cells and investigate the effect of NaBT
      on integrin expression and invasion. Integrin expression was assessed in the less
      invasive MIA-PaCa-2 and PANC-1 and more invasive L3.6, AsPC-1, and SUIT-2 human
      pancreatic cancer cell lines by ribonuclease (RNase) protection assay. Western
      blotting and immunofluorescent staining for beta4 expression was determined after
      NaBT treatment. Matrigel invasion chambers were used to assess pancreatic cancer
      cell invasion. beta4 and beta7 integrin expression was highest in L3.6, AsPC-1,
      and SUIT-2 cells. NaBT reduced the expression of beta4 integrin in AsPC-1 cells
      including less cell surface beta4. Invasion of AsPC-1 cells was also reduced by
      NaBT. Expression of beta4 is higher in more aggressive pancreatic cancer cells;
      NaBT inhibits beta4 expression and invasion. NaBT may represent a novel strategy
      to inhibit pancreatic cancer invasion and improve the prognosis of this deadly
      disease.

PMID- 14592660
TI  - Objective psychomotor skills assessment of experienced and novice flexible
      endoscopists with a virtual reality simulator.
AB  - The objective of this study was to determine whether the GI Mentor II virtual
      reality simulator can distinguish the psychomotor skills of intermediately
      experienced endoscopists from those of novices, and do so with a high level of
      consistency and reliability. A total of five intermediate and nine novice
      endoscopists were evaluated using the EndoBubble abstract psychomotor task. Each
      subject performed three repetitions of the task. Performance and error data were
      recorded for each trial. The intermediate group performed better than the novice
      group in each trial. The differences were significant in trial 1 for balloons
      popped (P=.001), completion time (P=.04), and errors (P=.03). Trial 2 showed
      significance only for balloons popped (P=.002). Trial 3 showed significance for
      balloons popped (P=.004) and errors (P=.008). The novice group showed significant
      improvement between trials 1 and 3 (P<0.05). No improvement was noted in the
      intermediate group. Measures of consistency and reliability were greater than 0.8
      in both groups with the exception of novice completion time where test-retest
      reliability was 0.74. The GI Mentor II simulator can distinguish between novice
      and intermediate endoscopists. The simulator assesses skills with levels of
      consistency and reliability required for high-stakes assessment.

PMID- 14592661
TI  - Epidemiology of surgically treated gastric cancer in the United States, 1988
      2000.
AB  - The incidence of gastric cancer and the need for subsequent surgery has been
      decreasing in the United States. However, very few population-based studies on
      the magnitude of these changes are available. The objective of the present study
      was to characterize temporal trends in the use of gastric resection in the
      treatment of gastric cancer. Patients with a primary diagnosis code for gastric
      cancer (N=105,887) and a procedure code for gastric resection (N=23,690) in the
      Nationwide Inpatient Sample for 1988-2000 were included. The Nationwide Inpatient
      Sample represents a 20% stratified random sample representative of all United
      States hospitals. Outcome variables included the overall incidence, in-hospital
      mortality rate, and length of stay. Rates of surgery are shown as the number of
      cases per 100,000 hospital discharges. Hospital volume was defined as follows:
      low volume (1 to 4 cases per year), medium volume (5 to 8 cases per year), and
      high volume (9 or more cases per year). Rates of gastric resection have shown a
      20% decline from 30 cases per 100,000 (1988-1989) to 24 cases per 100,000 (1999
      2000) (P=0.001). In-hospital mortality has not changed over the 13-year period
      and remains at 7.4%. There was significant variation in mortality across
      hospitals, with very low-volume centers having an 8.9% mortality rate, whereas
      very high-volume centers had a 6.4% mortality rate (P<0.001). The market share of
      gastric resections performed at high-volume centers increased a small amount from
      43% (1988-1989) to 48% (1999-2000) (P=0.023). Over the 13-year period, length of
      stay decreased from 15 days (interquartile range [IQR] 11-23) in 1988 to 11 days
      (interquartile range [IQR] 8-16) in 2000 (P<0.001). Rates of gastric resection
      for cancer have shown a modest decline over the past 13 years in the United
      States. Although the length of stay for these patients has decreased, no
      significant changes to in-hospital mortality have occurred. Given the declining
      rates of gastric cancer surgery, and the superior outcomes at high-volume
      centers, regionalization of care may improve mortality rates for this high-risk
      surgical procedure.

PMID- 14592662
TI  - A better cell cycle target for gene therapy of colorectal cancer: cyclin G.
AB  - The purpose of this study was to evaluate the overexpression of cyclin G in
      colorectal neoplasia, which may be a more frequent event than cyclin D1 during
      the cell cycle and thus may have a more enhanced therapeutic potential in
      treating colorectal cancer. Ninety formalin-fixed, paraffin-embedded human colon
      and rectal specimens were obtained from the Pathology Department of Norris Cancer
      Center/University of Southern California. The tissues had been obtained after
      surgical resection between 1995 and 2001, and had been processed by routine
      clinical histopathologic methods. Ninety-one percent of colorectal tumors had
      cyclin G overexpression. These cyclin-positive patients were evenly distributed
      between men and women, and between tumor locations, that is, 36% rectal tumors
      and 34% right-sided tumors. Thirty-two percent were well differentiated, and 66%
      were moderately differentiated. Thirty patients (38%) had stage I disease, 16
      (20%) had stage II disease, 25 (32%) had stage III, and seven (9%) had stage IV
      disease. Eight patients (10%) in this group had recurrent disease during follow
      up. There was no correlation between cyclin G overexpression and clinical and
      pathologic characteristics. Cyclin D1 overexpression was found to be present in
      only 42% of colorectal adenocarcinomas. There was no correlation between cyclin
      D1 overexpression and clinical and pathologic characteristics. The present study
      demonstrates that cyclin G overexpression is a frequent event in colorectal
      cancer. This frequent event in colorectal carcinogenesis may facilitate new
      therapeutic approaches acting as a target for gene therapy, possibly directed at
      downregulating cyclin G in colorectal cancer.

PMID- 14592664
TI  - Binding pancreaticojejunostomy: 150 consecutive cases without leakage.
AB  - The objective of this study was to verify the safety of a new technique termed
      "binding pancreaticojejunostomy" in a prospective cohort study.
      Pancreaticojejunal anastomostic leakage is a major cause of morbidity and
      mortality after pancreaticoduodenectomy. To prevent the development of pancreatic
      fistulas, we designed a special technique that we termed binding
      pancreaticojejunostomy. Binding pancreaticojejunostomy entails binding 3 cm of
      the serosamuscular sheath of the jejunum to the intussuscepted pancreatic stump.
      From January 1996 to May 2001, a total of 150 consecutive patients were treated
      with this type of pancreaticojejunostomy, including typical
      pancreaticoduodenectomy in 120, hepatopancreaticoduodenectomy in 17, pylorus
      preserving pancreaticoduodenectomy in 10, and duodenal-preserving resection of
      the head of the pancreas in three. None of the patients developed pancreatic
      fistulas. The overall morbidity was 31.3%. The following complications occurred:
      gastrointestinal bleeding in six, pulmonary infection in 12, wound infection in
      20, delayed gastric emptying in three, incision dehiscence in four, and hepatic
      insufficiency in two. The mean postoperative hospital stay was 19.8 +/- 5 days.
      Binding pancreaticojejunostomy is a safe, simple, and effective technique.

PMID- 14592663
TI  - Cystic pancreatic neoplasms: enucleate or resect?
AB  - Asymptomatic cystic pancreatic neoplasms are being detected by abdominal imaging
      with increasing frequency. Enucleation of small cystic neoplasms can be performed
      without recurrence but has been associated with a higher incidence of pancreatic
      fistula. Thus the procedure has been modified to include intraoperative
      ultrasound imaging and closure of the pancreatic defect. This analysis was
      performed to determine whether these modifications have improved operative
      outcome. Thirty patients with mucinous cystic neoplasms (n=16), serous
      cystadenomas (n=10), and cystic islet cell tumors (n=4) were studied. Enucleation
      was performed in 11 patients (7 with mucinous cystic neoplasms, 2 with serous
      cystadenomas and 2 with islet cell tumors), whereas 19 underwent resection of
      cystic tumors (pancreatoduodenectomy in 8 and distal pancreatectomy in 11). The
      mean groups did not differ with regard to age (57 years), gender (73% female),
      presentation (63% incidental), or site (43% head, neck, or uncinate). Patients
      undergoing enucleation had smaller tumors (2.2 vs. 4.7 cm, P<0.01) that were less
      likely to be in the tail (9% vs. 42%). Operative time was significantly shorter
      in the enucleation group (199 vs. 298 minutes, P<0.01). Blood loss also was
      significantly reduced in the enucleation group (114 vs. 450 ml, P<0.001).
      Pancreatic fistula rates (27% vs. 26%) and length of hospital stay (12.6 vs. 15.7
      days) were similar in the two groups. Enucleation of benign cystic pancreatic
      neoplasms reduces operative time and blood loss without increasing postoperative
      complications or length of stay. Therefore enucleation should be the standard
      operation for small benign cystic neoplasms in the uncinate, head, neck, and body
      of the pancreas.

PMID- 14592665
TI  - Induction of MIC-1/growth differentiation factor-15 following bile duct injury.
AB  - Macrophage inflammatory peptide-1 (MIC-1)/growth/differentiation factor-15 (GDF
      15) is a divergent member of the transforming growth factor-beta superfamily
      cloned by others and us. MIC-1/GDF-15 is expressed in the liver, breast, and
      colon. Studies have demonstrated a growth-inhibiting effect of MIC-1/GDF-15 on
      colon and breast cancer cell lines in vitro and on tumor growth in vivo. We
      previously reported that MIC-1 expression is rapidly induced after a wide variety
      of murine acute and chronic liver injuries including aniline dye administration.
      I hypothesized, therefore, that MIC-1/GDF-15 may be a mediator of biliary tract
      injury and could play a role in regulation of bile duct proliferation. C57BL/6
      mice underwent surgical ligation of the common bile duct. Northern blot analysis
      revealed a time-dependent induction of MIC-1/GDF-15 mRNA in the liver. In situ
      hybridization of liver sections for MIC-1/GDF-15 expression after bile duct
      ligation demonstrated a zone 1 or periportal expression pattern, consistent with
      expression of MIC-1 in periductular hepatocytes. Northern blot analysis of liver
      mRNA from patients with sclerosing cholangitis or cirrhosis also demonstrated
      enhanced expression of MIC-1/GDF-15. MIC-1/GDF-15 is expressed after bile duct
      injury in mice and humans. Taken together with the previously demonstrated growth
      inhibitory effects of MIC-1/GDF-15 on normal and transformed cells, MIC-1/GDF-15
      may play a role in regulation of bile duct proliferation and biliary tumor
      formation.

PMID- 14592666
TI  - Management of epiphrenic diverticula.
AB  - Epiphrenic diverticula are very rarely seen and are often associated with
      achalasia, esophageal body dysmotility, and a high resting lower esophageal
      sphincter pressure. The aim of this study was to evaluate the different treatment
      options for patients with epiphrenic diverticula. Patients with an epiphrenic
      diverticulum were divided into two treatment groups: surgical and nonsurgical.
      Retrospective chart review was performed, and a symptom questionnaire was
      created. There were six patients in the nonsurgical group and 11 patients in the
      surgical group. The mean follow-up was 26.4 months. Ten patients had a
      laparoscopic operation performed. One patient was operated on thoracoscopically
      and had to be converted to a thoracotomy. Two diverticula were inverted with good
      results. There was one postoperative esophageal leak where no myotomy was added.
      An empyema developed in another patient at 4 weeks after surgery. One patient, in
      whom no antireflux procedure was performed, reported postoperative heartburn.
      Patients in the nonsurgical group had smaller diverticula, were not good
      candidates for surgery, or were asymptomatic. Esophageal diverticula are very
      rarely seen. Asymptomatic patients may not require therapy. If surgery is
      performed and the diverticulum is large, it should be removed. The laparoscopic
      approach is the surgical treatment of choice. A long myotomy and an antireflux
      procedure should be added to avoid esophageal leakage at the line of repair and
      gastroesophageal reflux.

PMID- 14592667
TI  - Old and new TNM in carcinoma of the gastric antrum: analysis of our personal
      experience.
AB  - Various tumor node metastasis (TNM) classifications have been proposed for
      staging of gastric carcinoma, including the fourth edition of the TNM
      classification and the Japanese Research Society for Gastric Cancer (JRSGC)
      system. In 1997 the fifth edition of TNM classification introduced the concept of
      the number of metastatic lymph nodes. We review our experience with staging
      gastric cancer in light of both the fourth and fifth editions of the TNM
      classification system. From January 1986 to December 1997, we performed subtotal
      resection in 193 patients with carcinoma of the gastric antrum. A total of 147
      patients presented with criteria from the fifth TNM edition. We compared data
      from these patients with data from the fourth TNM edition. We analyzed 84 females
      and 63 males whose average age was 68.9 years. The average number of lymph nodes
      removed was 16.7. We used the Kaplan-Meier method to analyze survival. In
      accordance with the fourth TNM edition, we recorded 82 patients who were pN0, 36
      who were pN1, and 29 who were pN2; according to the fifth edition, 82 patients
      were pN0, 33 were pN1, 17 were pN2, and 15 were pN3. Average follow-up was 26.7
      months, and average survival was 56.9 months for N0 patients, 38.7 months for N1
      patients, and 24.5 months for N2 patients staged according to the fourth edition.
      According to the fifth edition, survival was 39.3 months for N1 patients, 33.6
      months for N2 patients, and 10.3 months for N3 patients. The survival curve was
      statistically different (P<0.001) between N0 and N1 patients according to the
      fourth edition; there was no significant difference between N1 and N2 patients.
      According to the fifth edition, the difference in survival probability was
      P<0.001 between N0 and N1 patients and N2 and N3 patients. The fifth TNM edition
      presents a greater ease of stratification in bringing together and mediating
      diverse cultural experiences between West and East. This staging lays the basis
      for a more accurate comparison between the groups.

PMID- 14592668
TI  - Unusual complications of long-term percutaneous gastrostomy tubes.
AB  - Percutaneous endoscopic gastrostomy (PEG) has been popular since it was
      introduced in 1980. Gastrostomy tubes left in place for long periods often result
      in unusual complications. Complications may also result from simply replacing a
      long-term indwelling tube. Five patients who had gastrostomy tubes in place for
      as long as 4 years are presented and their complications reviewed. Various
      methods used in treating these complications are discussed, and suggestions for
      their prevention are given. Gastrointestinal erosion and jejunal perforation
      following migration of the gastrostomy tube, persistent abdominal wall sinus
      tracts, and separation of the flange head with small bowel obstruction were
      encountered. Reinsertion of a gastrostomy tube through a tract prior to adequate
      maturation was also noted to lead to complications. Complications may result from
      gastrostomy tubes left in place for extended periods of time and during
      replacement procedures. Awareness of such complications along with education of
      caregivers and timely intervention by the endoscopist may prevent such
      occurrences. In some cases one can only hope to minimize morbidity.

PMID- 14592669
TI  - Laparoscopic enucleation of solitary true pancreatic cyst in an adult.
AB  - Solitary or true pancreatic cyst is a very rare pathologic condition; only a few
      cases are reported in literature. We report a case of a 22-year-old woman with a
      symptomatic true pancreatic cyst located in proximity to the pancreatic head,
      duodenum, vena cava, biliary tree, and right kidney, which was enucleated through
      a laparoscopic approach. Laparoscopic ultrasound imaging allowed the surgeon to
      better identify the morphology of the cyst and its relationship with the adjacent
      structures. The treatment is briefly reviewed and discussed.

PMID- 14592670
TI  - Surgical treatment of small bowel cancer: a 20-year single institution
      experience.
AB  - Small bowel malignancies are rare. The aims of this study were to evaluate the
      outcomes associated with surgical therapy for small bowel cancers and to define
      prognostic factors. The medical records of 96 consecutive patients with primary
      small bowel cancer (excluding lymphoma) treated at our institution over a 20 year
      period were reviewed. Survival was analyzed using the Kaplan-Meier method (mean
      follow-up period 57 months). Mean patient age was 56 years, and 58% of patients
      were male. Sixty percent of patients had an adenocarcinoma, 21% had a sarcoma,
      and 19% had a carcinoid tumor. The percentages of patients who underwent complete
      (curative) resection were 51%, 90%, and 50% for those with adenocarcinoma,
      sarcoma, and carcinoid tumor, respectively. For patients with adenocarcinoma who
      underwent curative resection, tumor (T) and node (N) stages were significant
      prognostic factors predicting overall survival. For patients with sarcomas who
      underwent curative resection, tumor grade was a significant prognostic factor
      predicting overall survival. The prognosis for patients with small intestinal
      carcinoid tumors is uniformly favorable. The prognosis for patients with sarcomas
      and adenocarcinomas is generally poor, although long-term survival is achieved by
      patients with favorable prognostic factors.

PMID- 14592671
TI  - Coexpression of carcinoembryonic antigen and E-cadherin in colorectal
      adenocarcinoma with liver metastasis.
AB  - Carcinoembryonic antigen (CEA) has been suggested as a metastatic activator in
      colorectal carcinoma, whereas the E-cadherin expression is downregulated in a
      variety of carcinomas. CEA and E-cadherin expressions were simultaneously
      assessed with regard to tumor progression in the various sites of colorectal
      carcinomas with liver metastasis. Twenty-six consecutive patients who had
      colorectal carcinoma with liver metastasis underwent curative surgery for primary
      tumor and liver metastasis. CEA and E-cadherin expression were identified on
      immunohistochemical staining using the labeled streptavidin-biotin method. Their
      mRNA expression was also detected by RT in situ PCR using one-step reverse
      transcription-polymerase chain reaction (RT-PCR). CEA and E-cadherin expression
      scores in the tumor center were greater than those in the tumor margin in both
      primary tumor and liver metastasis (P<0.001 to 0.006). CEA expression scores were
      closely associated with E-cadherin expression scores on the corresponding tumor
      site (P<0.001 to 0.017). CEA and E-cadherin mRNA expression was greatest in the
      hepatocytes adjacent to liver metastasis, next greatest in the primary tumor, and
      least in the liver metastasis (P<0.001 to 0.002). CEA mRNA expression was also
      closely correlated with E-cadherin mRNA expression in the primary tumor (P<0.001)
      and in the adjacent hepatocytes of the liver metastasis (P=0.018). Patients with
      a lesser CEA expression score in the liver metastasis margin appeared to have a
      longer disease-free survival period than did those with a greater CEA expression
      score. Expression of CEA and E-cadherin was closely correlated with the mRNA
      levels. Furthermore, these correlations may be implicated in the tumor
      progression of colorectal carcinoma considering their biological properties.

PMID- 14592672
TI  - Neonatal cholinergic lesions and development of exploration upon administration
      of the GABAa receptor agonist muscimol in preweaning rats.
AB  - Neonatal rats were administered 192 IgG-saporin (192 IgG-Sap), a selective
      cholinergic immunotoxin, on postnatal day (PND) 7. Behavioural responsiveness to
      muscimol, a GABAa receptor agonist, was then assessed using locomotor activity
      and object exploration tests on PND 18. In Experiment 1, 192 IgG-Sap-lesioned and
      control rats were injected with the GABAa agonist, muscimol, on PND 18 and tested
      in a standard open field test. Muscimol reduced rearing responses in both control
      and 192 IgG-Sap-lesioned animals whereas reduced wall-rearing responses occurred
      in control animals only. 192 IgG-Sap also reduced rearing and wall-rearing
      responses. In Experiment 2, muscimol effects were evaluated on PND 18 in a
      spatial open field test in which object exploration in addition to locomotion and
      rearing responses was assessed. Neonatal cholinergic lesion per se increased
      locomotion during object exploration while decreasing time spent exploring
      objects. Depressant effects of muscimol on object exploration were also evident.
      As a whole, these data provide evidence for (i) basal forebrain (BF) cholinergic
      control on locomotor activity and object exploration and (ii) GABAa-mediated
      regulation of selective behavioural patterns associated with locomotion and
      exploration in weaning rats. Neonatal cholinergic lesions, however, do not appear
      to alter reactivity to GABAergic agonists in juvenile rats.

PMID- 14592673
TI  - High-alcohol-drinking rats exhibit persistent freezing responses to discrete cues
      following Pavlovian fear conditioning.
AB  - We previously reported that high-alcohol-drinking (HAD) rats exhibited selective
      deficits in active avoidance learning and that those deficits were partially
      reversed by moderate doses of ethanol under certain training conditions
      [Pharmacol. Biochem. Behav. 75 (2003) 89]. In that study, we hypothesized that
      HAD deficits resulted from exaggerated fear in the conditioning context and that
      the anxiolytic properties of ethanol, along with prior exposure to the
      conditioning apparatus, were responsible for the facilitated avoidance learning
      that was observed in HAD rats following moderate doses of ethanol. The current
      study was designed to test whether HAD rats exhibit behaviors consistent with
      increased fear in aversive learning contexts. We used a standard Pavlovian fear
      conditioning paradigm to assess behavioral freezing in HAD (HAD-1 and HAD-2) and
      low-alcohol-drinking (LAD; LAD-1 and LAD-2) rats. No significant differences were
      observed between HAD-1 and HAD-2 or between LAD-1 and LAD-2 rats, indicating that
      the replicate lines performed similarly in this study. Both HAD and LAD rats
      exhibited robust fear conditioning during training. Although no differences were
      observed between HAD and LAD rats during fear training, HAD rats failed to
      extinguish freezing behavior in response to the discrete tone conditional
      stimulus during subsequent fear retention tests. Thus, HAD rats demonstrated
      prolonged cue-elicited fear that was resistant to extinction.

PMID- 14592674
TI  - Behavioral effects and anatomic correlates after brain injury: a progesterone
      dose-response study.
AB  - Evidence suggests that progesterone enhances functional recovery in rats after
      medial frontal cortical contusions; however, a high dose of progesterone
      exacerbates tissue loss in a stroke model when administered chronically (7-10
      days) prior to injury [Stroke 31 (2000) 1173)]. This study attempts to determine
      progesterone's dose-response effects on behavioral performance and GABA-A
      receptor expression following a cortical contusion. Male rats received injections
      of 0, 8, 16, or 32 mg/kg progesterone in 22.5% 2-hydroxypropyl-beta-cyclodextrin
      following cortical impact. Lesion 8 mg/kg and lesion 16 mg/kg groups displayed
      less thigmotaxis in the Morris water maze (MWM) than 0 and 32 mg/kg groups and
      were not significantly impaired relative to shams on other water maze measures.
      Increased variability in the 32 mg/kg group during somatosensory neglect testing
      was the only evidence indicating that a high dose of progesterone was disruptive
      to a few animals. These results suggest that low and moderate doses of
      progesterone are optimal for facilitating recovery of select behaviors and that
      postinjury progesterone treatment permits a wider dose range than preinjury
      treatment. Progesterone did not affect lesion size, but a strong negative
      correlation was observed between thalamic GABA-A receptor density and water maze
      performance. Future studies could explore causes for this relationship.

PMID- 14592675
TI  - Pharmacologic and sensorimotor components of satiation in cigarette smoking.
AB  - To examine mechanisms underlying satiation in cigarette smoking, 18 smokers
      received intravenous (i.v.) nicotine, alone or in combination with denicotinized
      cigarette smoke. Nicotine was administered using programmed presentations of
      either pulsed injections or continuous infusions, with i.v. saline serving as a
      control. A high-nicotine cigarette smoke condition (usual brand) was also
      presented. During each of the six test sessions, subjects were allowed to puff on
      their usual brands of cigarette ad libitum while the programmed satiation
      conditions were in force. Administration of i.v. nicotine caused a small
      suppression of ad libitum smoking behavior; denicotinized smoke produced a
      significantly larger reduction, showing that short-term satiation is more
      dependent on the presentation of smoke than delivery of nicotine per se. However,
      denicotinized smoke alone did not have as much effect as puffs from the usual
      brands of cigarettes. The combination of i.v. nicotine and denicotinized smoke
      puffs produced equivalent satiation to that of the usual brand. Cigarette craving
      and negative affect were partially relieved by iv nicotine presentations as well
      as by denicotinized smoke, and again the combination of i.v. nicotine and
      denicotinized smoke approximated the effects of the usual brand. The results of
      this study underscore the importance of both sensorimotor aspects of smoking and
      the pharmacologic effects of nicotine in tobacco dependence.

PMID- 14592676
TI  - Serotonergic and histaminergic mechanisms involved in intralipid drinking?
AB  - Some newer antipsychotic agents are associated with weight gain in humans and a
      hyperphagic response to intralipid solutions in rodents. To examine the possible
      contribution of serotonin (5-HT) and histamine (H) receptor blockade in
      antipsychotic-associated hyperphagia, rats were trained to drink a palatable,
      high-calorie fat emulsion (10% intralipid) during 30-min sessions and were tested
      following pretreatment with mepyramine (H1 receptor antagonist), metergoline (5
      HT(1/2) receptor antagonist), cyproheptadine (H1 and 5-HT(2A/2B/2C) and
      muscarinic receptor antagonist), SB 242084 (5-HT2C receptor antagonist) and an SB
      242084-mepyramine combination. Total intake and ingestive behaviour
      microstructure were measured. Mepyramine (10 mg/kg) reduced intake, as did
      metergoline (3.0 mg/kg). Cyproheptadine (0.1-1.0 mg/kg) increased intake and
      microstructural analysis suggests that this was due to increased numbers of
      clusters of licking. SB 242084 (3 mg/kg) reduced intake, either when administered
      alone, or in combination with mepyramine (1 mg/kg). In conclusion, simple
      antagonism of either H1 (mepyramine) or 5-HT(1/2) receptors (metergoline) alone
      was not sufficient to increase intake. Furthermore, combined blockade of H1 and 5
      HT2C receptors (SB 242084 and mepyramine) was also insufficient to produce
      hyperphagia. Conversely, simultaneous blockade of H1, 5-HT(2A/2C) and muscarinic
      receptors (cyproheptadine) led to a substantial hyperphagia and pattern of
      ingestive behaviour that was similar to that previously observed with some newer
      antipsychotic agents.

PMID- 14592677
TI  - GHB differentially affects morphine actions on motor activity and social
      behaviours in male mice.
AB  - There are several reports suggesting that gamma-hydroxybutyric acid (GHB)
      influences the endogenous opioid system. The present study aimed to investigate
      the effects of GHB on motor and social activities and to examine its influence on
      morphine's actions on these behaviours. In a first experiment, several doses of
      GHB were studied but only the highest (200 and 400 mg/kg) produced a decrease in
      spontaneous motor activity measured in an actimeter cage. When hyperactivity
      induced by injecting 50 mg/kg of morphine was evaluated, all the GHB doses
      efficiently counteracted this morphine action. Using the paradigm of isolation
      induced aggression, administration of 200 mg/kg of GHB significantly decreased
      threat and attack without impairing motor activity and, in addition, increased
      time spent in social contact. GHB increased morphine's suppression of threat or
      nonsocial exploratory behaviours. In conclusion, the interaction between GHB and
      the opioid systems was confirmed, with the drug having an additive effect on
      morphine-affected social behaviours but counteracting morphine-induced increases
      in motor activity.

PMID- 14592678
TI  - Transient behavioral sensitization to nicotine becomes long-lasting with
      monoamine oxidases inhibitors.
AB  - Drugs of abuse, such as D-amphetamine or nicotine, are generally considered as
      acting through an increased release of dopamine in a subcortical structure, the
      nucleus accumbens, thus inducing locomotor hyperactivity in rats. Following
      repeated treatments, the same drugs induce a progressive increase in locomotor
      response called behavioral sensitization. This process has been suggested to play
      a role in the acquisition and maintenance of addictive behaviors. Here we show
      that whereas behavioral sensitization to D-amphetamine (0.5 and 0.75 mg/kg) stays
      constant following three consecutive periods of withdrawal (15, 30 and 30 days),
      the same experimental conditions completely abolish behavioral sensitization to
      0.3 and 0.5 mg/kg nicotine. Indeed, following these periods of withdrawal,
      locomotor responses to nicotine are identical to those obtained at the first
      nicotine injection or after repeated saline injections. However, when a monoamine
      oxidases inhibitor (MAOI), tranylcypromine (3 mg/kg) or pargyline (30 mg/kg), is
      co-injected with nicotine, behavioral sensitization is maintained despite
      submission of the animals to the same withdrawal experimental design. Since
      tobacco smoke is known to contain many compounds including MAOIs, our data
      suggest that addictive properties of tobacco may not be limited to nicotine. We
      propose that MAOIs potentiate effects of nicotine on monoamines release.

PMID- 14592679
TI  - Effect of the gadolinium ion on body fluid regulation.
AB  - Both osmoreception and baroreception are thought to involve ion channels that are
      sensitive to changes in membrane stretch. We investigated the effect of a blocker
      of stretch-activated ion channels, the Gd3+ ion, on osmoregulatory and
      cardiovascular responses in the intact rat. Intracerebroventricular injection of
      50-100 nmol Gd3+ reduced thirst induced by various treatments. Similar doses also
      reduced intake of saline induced by various treatments. Intracerebroventricular
      injection of 100 nmol Gd3+ transiently increased arterial pressure and reduced
      the pressor response to intracerebroventricular angiotensin II (Ang II). Systemic
      administration of Gd3+ failed to alter thirst, except for a high dose (270
      micromol/kg) that induced illness. This high dose failed to prevent urinary
      hypertonicity and excretion of a load of hypertonic NaCl. Intravenous infusion of
      270 micromol/kg of Gd3+ reduced blood pressure and pressure responses to
      intravenous phenylephrine, but did not reduce the baroreceptor reflex control of
      heart rate. We conclude that the effects of Gd3+ on thirst and on the
      cardiovascular system are probably not due to a direct effect of the drug on
      stretch-sensitive ion channels. Instead, many of the effects of Gd3+ were
      compatible with blockade of voltage-gated Ca2+ channels.

PMID- 14592680
TI  - Sex-related differences in the enhancement of morphine antinociception by NMDA
      receptor antagonists in rats.
AB  - The effect of the N-methyl-D-aspartate (NMDA) receptor antagonists
      dextromethorphan (DEX), ketamine (KET), and MK-801 on morphine (MOR)-induced
      antinociception has been investigated in male and female rats. DEX (7.5, 15, and
      30 mg/kg), KET (0.75, 1.5, and 3 mg/kg), and MK-801 (0.075, 0.15, and 0.3 mg/kg)
      dose-dependently enhanced MOR-induced (3 mg/kg) analgesia in female rats. DEX and
      KET enhanced the peak effect, whereas MK-801 increased both magnitude and
      duration of analgesia. DEX also enhanced MOR-induced analgesia in male rats.
      However, the interaction was of less magnitude in male compared with female rats.
      The effects of KET and MK-801 on MOR-induced analgesia were negligible in male
      rats. A 3-mg/kg dose of MOR given alone produced greater analgesia in male than
      in female rats, but in the presence of NMDA antagonists, MOR elicited similar
      analgesic responses in both sexes.

PMID- 14592681
TI  - D,L-cis-2,3-Pyrrolidine dicarboxylate alters [3H]-L-glutamate binding and induces
      convulsions in mice.
AB  - This study investigated whether D,L-cis-2,3-Pyrrolidine dicarboxylate (D,L-cis
      2,3-PDC), a new glutamate analogue, alters glutamate binding to cerebral plasma
      membranes and whether N-methyl-D-aspartate (NMDA) receptors are involved in the
      convulsant effect of this compound. D,L-cis-2,3-PDC reduced sodium-independent
      [3H]-L-glutamate binding to lysed membrane preparations from adult rat cortex and
      had no effect on sodium-dependent glutamate binding. Intracerebroventricular
      administration of D,L-cis-2,3-PDC (7.5-25 nmol/5 microl) induced generalized
      tonic-clonic convulsions in mice in a dose-dependent manner. The coadministration
      of MK-801 (7 nmol/2.5 microl), with D,L-cis-2,3-PDC (16.5 nmol/2.5 microl), fully
      protected the animals against D,L-cis-2,3-PDC-induced convulsions, while the
      coadministration of DNQX (10 nmol/2.5 microl) increased the latency to
      convulsions but did not alter the percentage of animals that had convulsions.
      These results suggest that D,L-cis-2,3-PDC-induced effects are mediated
      predominantly by NMDA receptors.

PMID- 14592682
TI  - Reduction in distractibility with AF102B and THA in the macaque.
AB  - Distractibility in primates may be influenced by central cholinergic systems. Two
      cholinomimetics, the m-1 muscarinic agonist (+/-)-cis-2-methyl-spiro(1,3
      oxathiolane-5,3')quinuclidine (AF102B, civemeline) and the cholinesterase
      inhibitor tetrahydroaminoacridine (THA, tacrine), were compared to vehicle
      controls for effects on distractibility in an automated visuospatial attention
      task. The task required visual pursuit of a moving target amongst distractor
      stimuli that acted to impair performance and was executed by seven healthy adult
      bonnet macaque monkeys. Task accuracy and reaction time were measured 1.5 h after
      systemic administration of each substance. For the seven-subject group at
      individually titrated best doses, accuracy increased significantly relative to
      vehicle for both drugs. Reaction time at best dose decreased for both drugs, but
      not significantly. Muscarinic agonists and cholinesterase inhibitors may reduce
      distractibility in primates.

PMID- 14592683
TI  - Mecamylamine acutely increases human intravenous nicotine self-administration.
AB  - Previous studies of human cigarette smoking have shown that administration of the
      nicotinic acetylcholine receptor antagonist mecamylamine produces acute increases
      in smoking behavior. In contrast, studies of intravenous nicotine self
      administration in animals typically show an immediate decrease in self
      administration behavior following mecamylamine administration. To investigate
      whether this discrepancy might be due in part to the mode of nicotine self
      administration (intravenous vs. cigarette smoke), we measured the rate of
      intravenous nicotine self-administration in tobacco-dependent human smokers.
      After being trained in a preliminary session to self-administer puff-sized bolus
      doses of nicotine, 16 subjects were exposed to two sessions (4 h duration) in
      which they could self-administer intravenous nicotine ad lib. Two hours prior to
      one session, subjects swallowed a capsule containing 10 mg mecamylamine, and
      before the other session they took a placebo capsule. Rates of responding for
      nicotine were assessed, as were subjective reports of withdrawal symptoms and
      plasma nicotine levels. There was a significantly higher rate of nicotine self
      administration in the mecamylamine condition, and mecamylamine attenuated the
      reduction in craving over the session that occurred during nicotine self
      administration. These results indicate that route of administration is not likely
      the major source of the discrepancy between findings from animal and human
      studies of nicotine administration. Instead, it is likely that the higher rates
      of nicotine self-administration induced by mecamylamine were due to an
      attenuation of the effects of nicotine (e.g., alleviation of withdrawal symptoms)
      in nicotine-dependent subjects. Thus, animal models of nicotine dependence may
      need to be employed in conjunction with self-administration procedures in order
      to duplicate the effects of mecamylamine observed in studies of human smokers.

PMID- 14592684
TI  - Behavioral sensitization and long-term neurochemical alterations associated with
      the fungicide triadimefon.
AB  - Triadimefon (TDF), a widely used triazole fungicide, blocks reuptake of the
      neurotransmitter dopamine (DA), similarly to cocaine. Preliminary studies show
      that intermittent intraperitoneal injections of TDF increase ambulatory and
      vertical activity across repeated injections [Neurotoxicology (in press)] leading
      to the hypothesis tested here, that exposure to TDF may influence the development
      and expression of behavioral sensitization, a model of psychostimulant-induced
      psychosis. Exposure of adult male C57BL/6 mice to 75 mg/kg i.p. TDF (TDF75) twice
      a week for 7 weeks increased vertical activity at each injection. Following a 2
      week withdrawal period, a TDF challenge to test for expression of behavioral
      sensitization revealed further increases in vertical activity levels relative to
      all other conditions. TDF induction/expression of behavioral sensitization was
      associated with long-term, perhaps permanent modulation of dopaminergic function
      that included increases in striatal dihydroxyphenylacetic acid (DOPAC) and DA
      turnover, increases in medial prefrontal cortex (mPFC) dopamine transporter (DAT)
      binding, as well as decreases in DA D1 and increases in DA D2 and DAT receptor
      binding that appeared to target the nucleus accumbens shell (NAs) subregion.
      Thus, TDF exposure may serve as an environmental risk factor for DA system
      dysfunctions.

PMID- 14592685
TI  - Interaction between estradiol replacement and chronic stress on feeding behavior
      and on serum leptin.
AB  - Exposure to stress may cause either an increase or a decrease in food intake.
      Behavioral and physiological responses to stress, including alterations in
      feeding behavior, are sexually dimorphic. This study aimed to evaluate the
      interaction between estradiol levels and chronic variate stress on the intake of
      sweet food and on serum levels of leptin, a hormone secreted by the adipose cells
      with a role in the regulation of body weight. Adult female Wistar rats were used.
      After ovariectomy, the animals received estradiol replacement (or oil)
      subcutaneously. Rats were then divided in controls and stressed (submitted to 30
      days of variate stress). Consumption of sweet food and of serum leptin was
      measured. Although animals receiving estradiol replacement presented smaller
      weight gain, they showed an increased consumption of sweet food. Chronic variate
      stress decreased sweet food intake at 30, but not at 20, days of treatment.
      Estradiol replacement in the stressed group prevented both the reduction observed
      in sweet food intake and the increase in leptin levels. These results suggest
      that there is an interaction between chronic stress and estradiol replacement in
      feeding behavior concerning sweet food consumption, and this interaction may be
      related to altered leptin levels.

PMID- 14592686
TI  - Chronic D1 agonist and ethanol coadministration facilitate ethanol-mediated
      behaviors.
AB  - Separate lines of evidence suggest that neuroadaptations associated with ethanol
      (EtOH) reinforcement can be initiated by chronic EtOH preexposure and a signaling
      pathway activated by dopamine (DA) D1 receptor stimulation. We have previously
      shown that rewarding and locomotor effects of EtOH alone [Pharmacol. Biochem.
      Behav. 72 (2002) 787] are enhanced after chronic exposure to self-administered
      EtOH/cocaine combinations. To determine the importance of chronic EtOH exposure,
      dopamine D1 receptor activation and mode of drug administration in EtOH reward,
      animals were given daily intravenous infusions of experimenter-administered
      saline, EtOH (2.0 g/kg), the DA D1 receptor agonist, SKF81297 (0.2 mg/kg), or
      EtOH+SKF81297 over a 4-week period. Compared to other groups, animals preexposed
      to EtOH+SKF81297 self-administered significantly greater amounts of intravenous
      EtOH and showed greater enhancement and less suppression of locomotor activity in
      response to a range of intravenous EtOH dosages (0.125, 0.25, 0.5, 1.0 and 1.5
      g/kg). Since chronic treatment with EtOH alone did not enhance EtOH-induced
      reinforcement or locomotor activity, it is unlikely that these effects were due
      to EtOH tolerance. These findings suggest that chronic D1 receptor activation
      combined with EtOH administration alters neural responsiveness to EtOH and
      support the notion that D1 activation is important to EtOH reward.

PMID- 14592687
TI  - Chronic stress alters behavior in the conditioned defensive burying test: role of
      the posterior paraventricular thalamus.
AB  - In the present studies, we examined the effects of chronic restraint on behavior
      in the conditioned defensive burying paradigm, a well-validated test of anxiety.
      This test is based on the findings that rodents tend to cover or bury the source
      of a noxious or aversive stimulus. However, little is known about whether prior
      chronic stress exposure can alter this anxiety-related behavior. In the present
      study, we examined whether chronic restraint affects indices of behavior in the
      conditioned defensive burying paradigm. Furthermore, since the posterior division
      of the paraventricular thalamus (pPVTh) regulates neuroendocrine activity
      specifically in chronically stressed but not control rats, we hypothesized that
      the pPVTh may also regulate any chronic stress-induced changes in behavior
      observed in the defensive burying test. Chronically stressed rats (30-min
      restraint per day for seven consecutive days) exhibited decreased latency to bury
      compared to control rats regardless of the presence of lesions suggesting
      increased reactivity to the shock in these animals. Importantly, pPVTh-lesioned
      chronically stressed rats exhibited increased duration and height of burying
      compared to control rats with pPVTh lesions, whereas no differences existed
      between sham-lesioned control and chronically stressed rats. Since both burying
      height and duration of burying are considered indices of anxiety in the defensive
      burying test, the present results suggest that the intact pPVTh may be important
      in dampening behaviors related to anxiety in chronically stressed rats.

PMID- 14592688
TI  - Altered reward value of carbohydrate snacks for female smokers withdrawn from
      nicotine.
AB  - Discontinuing nicotine intake usually results in weight gain partially due to
      heightened energy intake from between-meal snacks. This experiment tested the
      hypothesis that the reinforcing value of palatable carbohydrate-rich snacks
      increases for female smokers during nicotine deprivation. Eighteen smokers and 18
      nonsmokers completed a concurrent-schedules operant computer task on two separate
      days. Smokers were bioverified abstinent at the second testing. The operant task
      allowed participants to earn points redeemable for either carbohydrate snacks or
      money on concurrent variable-ratio schedules of reinforcement. There were five
      different probabilities of earning points redeemable for snacks (8%, 16%, 25%,
      50%, 75%), while the probability of earning points redeemable for money remained
      fixed at 25%. Reward value of snacks was measured by switch point: the
      reinforcement ratio at which the effort required to earn snacks exceeded their
      value to the respondent, as signified by a shift to working for money. Results
      showed that smokers undergoing nicotine deprivation persisted in working for
      snacks into leaner reinforcement schedules than nonsmokers (P=.026). Furthermore,
      nicotine deprivation increased smokers' allocation of effort to earn snack foods
      relative to their own behavior when smoking (P=.006). Variation in palatability
      or hunger did not explain these differences in snack reward value. Findings
      indicate that nicotine deprivation is associated with a heightened reward value
      of appealing snack foods for female smokers.

PMID- 14592689
TI  - Effects of NMDA receptor antagonists on acute mu-opioid analgesia in the rat.
AB  - Mixed research findings have led to a debate regarding the effect of N-methyl-D
      aspartate (NMDA) receptor antagonists on opiate analgesia. NMDA antagonists have
      been found in various studies to enhance, to inhibit, or to have no effect on
      opiate analgesia. The present research used a single protocol to explore the
      effects of six NMDA receptor antagonists on acute morphine (3.0 mg/kg s.c.) and
      fentanyl (0.05 mg/kg s.c.) analgesia in adult male Sprague-Dawley rats. NMDA
      receptor antagonists were selected based on their abilities to block various
      sites on the NMDA receptor complex, including the noncompetitive antagonists MK
      801 (0.1 and 0.3 mg/kg i.p.), dextromethorphan (10.0 and 30.0 mg/kg i.p.), and
      memantine (3.0 and 10.0 mg/kg i.p.), a glycine site antagonist, (+)-HA-966 (10.0
      and 30.0 mg/kg i.p.), a competitive antagonist, LY235959 (1.0 and 3.0 mg/kg
      i.p.), and a polyamine site antagonist, ifenprodil (1.0 and 3.0 mg/kg i.p.).
      Analgesia was assessed using the tail-flick test. A single dose of each opiate
      was used. The low doses of the antagonists, which are known to produce
      significant neural and behavioral actions at NMDA receptors, had no effect on
      morphine or fentanyl analgesia. At the higher doses, morphine analgesia was
      significantly enhanced by LY235959 (3.0 mg/kg), and fentanyl analgesia was
      significantly enhanced by LY235959 (3.0 mg/kg), dextromethorphan (30.0 mg/kg),
      and (+)-HA-966 (30.0 mg/kg). Enhancement of analgesia occurred without any
      apparent adverse side effects. None of the NMDA antagonists affected tail-flick
      responses on their own, except the higher dose of LY235959 (3.0 mg/kg), which
      produced a mild analgesic effect. Because no consistent effects were observed,
      the data suggest that NMDA receptors are not involved in acute mu-opioid
      analgesia. The mechanisms underlying the enhancement of opiate analgesia by
      selected NMDA antagonists, such as LY235959, dextromethorphan, and (+)-HA-966,
      remain to be determined.

PMID- 14592690
TI  - Morphine-induced conditioned taste aversions: assessment of sexual dimorphism.
AB  - Although sex differences in taste aversions have been reported with emetics such
      as lithium chloride (LiCl), little is known whether such findings generalize to
      other aversion-inducing drugs, including recreational compounds. One particular
      class of recreational compounds that induces taste aversions but that has not
      been examined for sex differences in its aversive properties is the opioids. To
      assess sex differences in the aversive properties of the opioids, Experiment 1
      examined the acquisition and extinction of morphine-induced taste aversions in
      male and female rats. To determine whether the specific parametric conditions
      used in Experiment 1 would support sex differences in general, Experiment 2
      examined possible sex differences in the acquisition and extinction of LiCl
      induced taste aversions, a compound for which sex differences have been
      previously reported. During acquisition, male and female rats were given 20-min
      access to a novel saccharin solution and injected with either morphine (0, 10, 18
      and 32 mg/kg s.c.; Experiment 1) or LiCl (0, 0.3, 0.6 and 1.2 mEq s.c.;
      Experiment 2) every fourth day for a total of four conditioning trials. During
      extinction, subjects were allowed access to saccharin but were not injected (for
      a total of eight trials). There were no sex differences in acquisition with
      either morphine or LiCl. There were also no sex differences in extinction with
      morphine; however, sex differences were found with LiCl, an effect consistent
      with prior assessments with this drug. The basis for and implications of the
      differences in the effects of sex on morphine- and LiCl-induced taste aversions
      were discussed.

PMID- 14592691
TI  - Physicochemical investigation of the effects of water-soluble polymers on
      vinpocetine complexation with beta-cyclodextrin and its sulfobutyl ether
      derivative in solution and solid state.
AB  - The studies reported in this work aimed to elucidate the inclusion complex
      formation of vinpocetine (VP), a poorly water-soluble base type drug, with beta
      cyclodextrin (betaCD) and its sulfobutyl ether derivative (sulfobutyl ether beta
      cyclodextrin (SBEbetaCD)), with or without water-soluble polymers (PVP and HPMC),
      by thoroughly investigating their interactions in solution and solid state. Phase
      solubility studies were carried out to evaluate the solubilizing power of both
      cyclodextrins (CDs), in association with water-soluble polymers, towards VP and
      to determine the apparent stability constants (Kc) of the complexes. SBEbetaCD
      showed higher solubilizing efficacy toward VP than the parent betaCD due to its
      greater solubility and complexing abilities, what was reflected in higher Kc
      values. Improvement in Kc values for ternary complexes clearly proves the benefit
      on the addition of water-soluble polymers to promote higher complexation
      efficiency. VP-CDs (1:1) binary and ternary systems were prepared by physical
      mixing, kneading, co-evaporation, and lyophilization methods. In the solid state,
      drug-carrier interactions were studied by scanning electron microscopy (SEM),
      differential scanning calorimetry (DSC), X-ray diffractometry (XRD) and Fourier
      transform infrared spectroscopy. The results of these analysis suggested the
      formation of new solid phases, some of them in amorphous state, allowing to the
      conclusion of strong evidences of binary and ternary inclusion complex formation
      between VP, CD and water-soluble polymers, particularly for co-evaporated and
      lyophilized binary and ternary products.

PMID- 14592692
TI  - Synthesis and cytotoxicity of substituted 2-benzylnaphth[2,3-d]imidazoles.
AB  - Designed as a new series of so called "bivalent ligand" containing the proposed 2
      benzylnaphthimidazole-type structure, a number of 2-benzylnaphth[2,3
      d]imidazoles, bearing various substituents, have been prepared by a synthetic
      approach involving an heterocyclization of 2,3-diaminonaphthalene 4 with
      appropriate imidates 3 (for 1b-i) followed by alkylation (for 1j-l) with the
      desired alkylating agent. Compounds 1b-f, h-l were subjected to primary
      biological evaluation for cancer cell growth inhibition (one-dose, three-cell
      assay), and the four most active terms, 1c, h, i and j, were then evaluated for
      their cytotoxic profiles in the National Cancer Institute's (NCI) human disease
      oriented, 60 cell line, in vitro antitumor screening protocol. Among them, two
      compounds (1h and 1i) are the most representatives demonstrating not only high
      growth-inhibitory activities against some leukemia cancer cells, but also fairly
      good activities against the growth of certain cell lines of some solid tumors.

PMID- 14592693
TI  - A new process control strategy for aqueous film coating of pellets in fluidised
      bed.
AB  - The parameters with effect on maximum spray rate and maximum relative outlet air
      humidity when coating pellets in a fluidised bed were investigated. The tested
      variables include type of water based modified release film coating (Eudragit NE
      30D, Eudragit RS 30D, Aquacoat ECD) coating principle (top spray, bottom spray),
      inlet air humidity and type of pellets (sugar spheres, microcrystalline cellulose
      pellets). The maximum spray rate was not influenced by the coating principles.
      The highest spray rate was obtained for the film polymer with the lowest
      tackiness which is assumed to be the controlling factor. The type of pellets
      affected the maximum spray rate. A thermodynamic model for the coating process is
      employed throughout the process and not just during steady state. The
      thermodynamic model is incorporated into a new process control strategy. The
      process control strategy is based on in-process calculation of degree of
      utilisation of the potential evaporation energy (DUE) of the outlet air and the
      relative outlet air humidity (RH). The spray rate is maximised using set points
      of DUE and RH as control parameters. The product temperature is controlled
      simultaneously by regulating the inlet air temperature.

PMID- 14592694
TI  - The effect of pH and triethanolamine on sulfisoxazole complexation with
      hydroxypropyl-beta-cyclodextrin.
AB  - A novel complexation of sulfisoxazole with hydroxypropyl-beta-cyclodextrin (HP
      beta-CD) was studied. Two systems were used: binary complexes prepared with HP
      beta-CD and multicomponent system (HP-beta-CD and the basic compound
      triethanolamine (TEA)). Inclusion complex formation in aqueous solutions and in
      solid state were investigated by the solubility method, thermal analysis
      (differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA)),
      Fourier-transform infrared spectroscopy (FT-IR) and dissolution studies. The
      solid complexes of sulfisoxazole were prepared by freeze-drying the homogeneous
      concentrated aqueous solutions in molar ratios of sulfisoxazole:HP-beta-CD 1:1
      and 1:2, and sulfisoxazole:TEA:HP-beta-CD 1:1:2. FT-IR and thermal analysis
      showed differences among sulfisoxazole:HP-beta-CD and sulfisoxazole:TEA:HP-beta
      CD and their corresponding physical mixtures and individual components. The HP
      beta-CD solubilization of sulfisoxazole could be improved by ionization of the
      drug molecule through pH adjustments. However, larger improvements of the HP-beta
      CD solubilization are obtained when multicomponent systems are used, allowing to
      reduce the amount of CD necessary to prepare the target formulation.

PMID- 14592695
TI  - Spray freezing into liquid (SFL) particle engineering technology to enhance
      dissolution of poorly water soluble drugs: organic solvent versus organic/aqueous
      co-solvent systems.
AB  - A spray freezing into liquid (SFL) particle engineering technology has been
      developed to produce micronized powders to enhance the dissolution of poorly
      water soluble active pharmaceutical ingredients (APIs). Previously, a
      tetrahydrofuran (THF)/water co-solvent was used as the solution source in the SFL
      process. In the present study, an organic system was developed to further enhance
      the properties of particles produced by SFL. The influence of solution type (e.g.
      organic versus organic/water) on the physicochemical properties of SFL powders
      was investigated and compared. The physicochemical properties of SFL
      carbamazepine (CBZ)/poloxamer 407/PVP K15 (2:1:1 ratio) powders were
      characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM),
      particle size distribution, surface area analysis, contact angle measurement,
      Karl-Fisher (KF) titration, gas chromatography (GC) analysis, HPLC analysis, and
      dissolution testing. The CBZ loading in the feed solution of the SFL acetonitrile
      system was 2.2% (w/w), which was greater than 0.22% (w/w) loading of the
      THF/water co-solvent system. XRD results indicated CBZ was amorphous in SFL
      powders produced by either system. SEM micrographs indicated that SFL powders
      from acetonitrile appeared less porous with a smaller primary particle size than
      particles from the co-solvent. The M50 (50% cumulative percent undersize) of
      micronized powder from the SFL acetonitrile system and the THF/water co-solvent
      system with 0.22% CBZ loading were 680nm and 7.06microm, respectively. The
      surface area of SFL powders from the acetonitrile and co-solvent systems were
      12.89 and 13.31m(2)/g, respectively. The contact angle of the SFL powders against
      purified water was about 35 degrees for both systems. The SFL powders from both
      systems exhibited similar and significantly enhanced dissolution rates compared
      to the bulk CBZ. Acetonitrile was an effective alternative solvent to THF/water
      co-solvent for use with the SFL micronization process to produce free flowing
      particles containing CBZ with significantly enhanced wetting and dissolution
      properties.

PMID- 14592696
TI  - Characterization of solid-state forms of celecoxib.
AB  - This study deals with the generation and characterization of various solid-state
      forms of celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor. The drug was
      subjected to polymorphic screen using different solvents to explore the
      possibility of existence of different solid forms. N,N-Dimethyl acetamide (DMA)
      and N,N-dimethyl formamide (DMF) yielded solvates in 1:1 stoichiometric ratio.
      Quench cooling of the melt resulted in amorphous form of the drug. All these
      solid-state forms were characterized by thermoanalytical (DSC, TGA, HSM),
      crystallographic (XRD), microscopic (polarized, SEM), spectroscopic (FTIR), and
      elemental analysis techniques. Solubility and van't Hoff studies were carried out
      for their thermodynamic interpretation. Influence of morphology of different
      solid-state forms on flow behavior was also investigated. Molecular modeling
      studies were used to elucidate the interaction between solute and solvent
      molecules in the solvate.

PMID- 14592697
TI  - Permeation of ciclopirox across porcine hoof membrane: effect of pressure
      sensitive adhesives and vehicles.
AB  - The purpose of this study was to investigate the effects of various pressure
      sensitive adhesives (PSA) on the penetration of ciclopirox across porcine hoof
      membrane. In addition, the influence of various vehicles on the permeation of
      ciclopirox from a PSA matrix across porcine hoof membrane was evaluated using a
      plastic penetration chamber containing poloxamer gel at 32 degrees C. Ciclopirox
      in poloxamer gel was extracted, derivatized and analyzed by HPLC. Ciclopirox
      showed highest permeability from an acrylic adhesive with a hydroxyl functional
      group, and this was followed by styrene-isoprene-styrene, styrene-butadiene
      styrene, silicone and polyisobutylene adhesives in order. In addition, N-methyl-2
      pyrrolidone (NMP), polypropylene glycol 400 (PPG 400), dimethylsulfoxide (DMSO),
      Labrasol, mercaptoethanol and Transcutol showed excellent permeation enhancing
      effects in a styrene-isoprene-styrene adhesive. A porcine hoof membrane treated
      with NMP changed from the non-helical phase to the helical phase, and another
      treated with DMSO showed a S=O peak shift to lower wavelength.

PMID- 14592698
TI  - In vitro and in vivo evaluation of a new sublingual tablet system for rapid
      oromucosal absorption using fentanyl citrate as the active substance.
AB  - Oromucosal delivery of drugs promotes rapid absorption and high bioavailability,
      with subsequent almost immediate onset of pharmacological effect. However, many
      oromucosal delivery systems are compromised by the possibility of the patient
      swallowing the active substance before it has been released and absorbed locally
      into the systemic circulation. This paper introduces a new tablet system for
      sublingual administration and rapid drug absorption. The tablet is based on
      interactive mixtures of components, consisting of carrier particles partially
      covered by fine dry particles of the drug, in this case fentanyl citrate. In the
      interests of increasing retention of the drug at the site of absorption in the
      oral cavity, a bioadhesive component was also added to the carrier particles.
      Tablets containing 100, 200 and 400 microg of fentanyl were tested both in vitro
      and in vivo. The tablets disintegrated rapidly and dissolution tests revealed
      that fentanyl citrate was dissolved from the formulation almost instantly. Plasma
      concentrations of fentanyl were obtained within 10 min, with no second peak.
      These results indicated that the bioadhesive component prevented the fentanyl
      from being swallowed (the fraction swallowed was considered smaller compared to
      other mucosal delivery systems), without hindering its release and absorption.
      This new sublingual tablet formulation may also hold potential for other
      substances where a rapid onset of effect is desirable.

PMID- 14592699
TI  - The dosing solution influence on the pharmacokinetics of degarelix, a new GnRH
      antagonist, after s.c. administration to beagle dogs.
AB  - OBJECTIVE: Degarelix (FE200486) is a new GnRH-receptor antagonist intended for
      the treatment of prostate cancer. The objective of the present analysis was to
      evaluate the pharmacokinetics of degarelix after subcutaneous (s.c.) and intra
      muscular (i.m.) administration to male beagle dogs, and to determine the
      influence of the different dosing conditions on the absorption profile of
      degarelix. METHODS: Degarelix was administered to 27 dogs and plasma
      concentrations were measured. The dosing conditions varied with respect to route
      (s.c. or i.m.), dose (0.25-1.5 mg/kg), solution strength (1.25-40 mg/ml) and
      volume administered (0.15-2.9 ml). Data were analysed by use of non-linear mixed
      effect modelling to characterize the pharmacokinetics, in particular the
      relationship between dosing conditions and rate, and extent of absorption.
      RESULTS: After s.c. and i.m. administration of degarelix, the plasma
      concentration versus time profile was best described by applying a two
      compartment model, with two input functions: a fast first-order input function to
      describe the rapid initial increase in the plasma concentration levels, and a
      slow first-order input function to describe the prolonged absorption profile of
      degarelix. Intra-muscular as opposed to s.c. administration led to a more rapid
      absorption of degarelix, reaching a mean maximum concentration of 64 and 31 ng/ml
      roughly 2.0 and 3.7 h after administration, respectively. The slow absorption
      half-life was found to be 268 h ( approximately 11 days). The relative fraction
      absorbed was found to vary with the concentration of the dosing solution. The
      present analysis suggested that the absorbed fraction was reduced by
      approximately 50% when the concentration in dosing solution was increased from
      1.25 to 40 mg/ml. The rate of the initial absorption component was also dependent
      on the concentration in the dosing solution, with slower absorption at higher
      concentrations. CONCLUSION: Through varying the dosing conditions and by applying
      a joint analysis of all data, the important factors determining the complex
      absorption of degarelix could be described.

PMID- 14592700
TI  - Synthesis and anticonvulsant and neurotoxicity evaluation of N4-phthalimido
      phenyl (thio) semicarbazides.
AB  - The phenyl (thio) semicarbazide derivatives of phthalimido pharmacophore were
      synthesized and evaluated for their anticonvulsant and neurotoxic properties.
      Initial anticonvulsant screening was performed using intraperitoneal (i.p.),
      maximal electroshock-induced seizure (MES), subcutaneous pentylenetetrazole
      (scPTZ) and subcutaneous strychnine (sc STY)-induced seizure threshold tests in
      mice. Compound 2c afforded protection in all the three screens. Compounds except
      1d, 2a and 2d showed no neurotoxicity up to 300 mg/kg. Compounds 1a, 1b, 2c, 2d,
      2g and 2i were found to show oral MES activity. The compounds exhibited CNS
      depression and behavioral despair side effects, lesser than the conventional
      antiepileptic drugs.

PMID- 14592701
TI  - Blood-brain barrier transport of synthetic adenosine A1 receptor agonists in
      vitro: structure transport relationships.
AB  - Transport of 11 structurally related adenosine A(1) receptor agonists was
      determined in an in vitro BBB model of brain-capillary-endothelial-cells and
      astrocytes. Inhibitor S-(4-nitrobenzyl)-6-thioinosine (NBTI) was used to quantify
      the contribution of the es nucleoside transporter to the overall transport. The
      N(6)-substituted adenosine analogues N(6)-cyclobutyladenosine (CBA), N(6)
      cyclopentyladenosine (CPA) and N(6)-cyclohexyladenosine (CHA) showed
      concentration-dependent clearance and their transport could be inhibited by NBTI.
      The V(max) was 1.5+/-0.2 pmol min(-1) and the Km values were 2.2+/-0.2, 1.8+/-0.3
      and 15+/-4 microM for CBA, CPA and CHA, respectively. Further chemical
      modification such as substitution in the C8-position or modification at the
      ribose-moiety resulted in loss of affinity for the es nucleoside transporter.
      Transport by passive diffusion was slow with clearances ranging from 0.21+/-0.01
      microl min(-1) for 8-(methylamino)-CPA (MCPA) to 1.8+/-0.18 microl min(-1) for 5'
      deoxy-CPA (5'dCPA). Regression analysis showed no relationship between transport
      clearance by passive diffusion and the GTP-shift, a non-linear relationship
      between the transport clearance by passive diffusion and the dynamic polar
      surface area (Cl=0.469e(-0.071DPSA); R2=0.88) and a linear relationship between
      transport clearance and prediction of BBB transport on basis of the Abraham
      equation (logCl=1.53logBB-1.56; R2=0.83). It is concluded that the transport of
      synthetic A(1) adenosine derivatives across the blood-brain barrier is generally
      quite slow. In addition, transport by the es nucleoside transporter may
      contribute to the transport of certain structurally distinct analogues.

PMID- 14592702
TI  - Development of tolerance to the inhibitory effect of loperamide on
      gastrointestinal transit in mice.
AB  - The inhibitory effect of repetitiously administered loperamide, a peripheral mu
      opioid receptor agonist and well-recognized antidiarrheal agent, on mouse
      gastrointestinal transit was compared with that of morphine in order to examine
      the development of tolerance to mu-opioid receptor agonist-induced constipation
      (antitransit effect). When administered subcutaneously 15 min before the oral
      injection of charcoal meal, loperamide (0.1-30 mg/kg) and morphine (1-8 mg/kg)
      dose-dependently and significantly inhibited gastrointestinal transit of charcoal
      with the ID(50) values of 1.6 (0.3-7.1) mg/kg and 3.6 (1.5-8.5) mg/kg,
      respectively. When loperamide (30 mg/kg) was administered twice daily for 2 days,
      the antitransit effect was significantly reduced. On the other hand, morphine did
      not develop tolerance in even more severe conditions than those of loperamide. It
      is known that P-glycoprotein, an ATP-dependent drug efflux pump, is involved in
      the development of tolerance to morphine analgesia. The tolerance observed with
      loperamide was significantly prevented by cyclosporin (30 mg/kg, i.p.), a P
      glycoprotein inhibitor, thus the ID(50) value in loperamide-tolerant mice was
      markedly reduced from >1000 mg/kg to 40 (2.7-603.0) mg/kg by cyclosporin. These
      results indicate that loperamide, different from morphine, readily develops
      tolerance to the inhibitory effect on mouse gastrointestinal transit, and the P
      glycoprotein may be involved in the development of tolerance to the antitransit
      effect of loperamide.

PMID- 14592703
TI  - Detection and typing of Borrelia burgdorferi sensu lato genospecies in Ixodes
      persulcatus ticks in West Siberia, Russia.
AB  - The prevalence of Borrelia burgdorferi sensu lato (s.l.) genospecies in West
      Siberia as well as in many other regions of Russia remains insufficiently
      investigated. In the present study a total of 151 adult female ticks Ixodes
      persulcatus Schulze, collected at three localities in eastern regions of West
      Siberia, where Lyme disease is endemic, were examined for the presence of the
      spirochete B. burgdorferi s.l. by polymerase chain reaction targeting the 23S-5S
      rRNA intergenic spacer regions. Spirochetal DNA was detected in on average 15.2+/
      3.0% of the ticks examined. The infection rate of adult ticks with B. burgdorferi
      s.l. at various localities ranged from 8.6+/-3.4% to 29.0+/-7.6%, being greatest
      in the northernmost site studied and decreasing southwards. The restriction
      patterns obtained after MseI digestion of the 23S-5S rRNA intergenic spacer
      amplicons assigned 23 DNA samples to the following genomic groups: 19 to B.
      garinii (12 to group NT29 and seven to group 20047(T)), three to B. afzelii, and
      one to mixed B. afzelii and B. garinii NT29. We have not detected other
      genospecies, which were found in ticks in Europe, the Russian Far East and Japan.
      Thus, the ticks examined were associated only with two genospecies of Borrelia
      burgdorferi s.l. pathogenic to humans (B. garinii and B. afzelii), and B. garinii
      was the major genospecies infecting adult I. persulcatus in eastern regions of
      West Siberia.

PMID- 14592704
TI  - Ambient pH controls the expression of endopolygalacturonase genes in the
      necrotrophic fungus Sclerotinia sclerotiorum.
AB  - In the necrotrophic fungus Sclerotinia sclerotiorum, secretion of
      polygalacturonases (PGs) and decrease of the environmental pH via oxalic acid
      production are considered as the main pathogenicity determinants. In order to
      evaluate the relationship between these two aspects of the infection process, we
      analyzed the expression of the endoPG-encoding genes pg1-3. Transcription of pg1
      3 was not carbon regulated but was strictly controlled by pH and highly favored
      in a narrow range of acidic pH. During plant infection, a pH gradient was
      established in relation to oxalic acid secretion. Transcripts of pg1-3 were
      localized to the zone of colonization of healthy tissues while transcripts of
      genes encoding other lytic enzymes were restricted to the more acidic zones of
      the infected tissues. Our results show that progressive acidification of the
      ambient medium by the fungus is a major strategy for the sequential expression of
      pathogenicity factors.

PMID- 14592705
TI  - Isoniazid resistance of exponentially growing Mycobacterium smegmatis biofilm
      culture.
AB  - Biofilm growth of Mycobacterium smegmatis was found to be unaffected at an
      isoniazid concentration that inhibited growth of planktonic bacilli (i.e. at
      isoniazid minimum inhibitory concentration=10 microg ml(-1)). Significant growth
      (50% of drug-free control) of biofilms was observed at up to 40 microg ml(-1) and
      the MIC for biofilm growth showed an increase to up to 80 microg ml(-1)
      isoniazid. Thus, the biofilm growth modus appears to be a strategy for
      replicating bacilli to evade the onslaught of antibacterials.

PMID- 14592706
TI  - A comparative study between an endoglucanase IV and its fused protein complex
      Cel5-CBM6.
AB  - The recombinant endoglucanase IV (Cel5; encoded by egIV) of Ruminococcus albus
      was compared with protein Cel5-CBM6 comprised of Cel5 fused at the C-terminus
      with the single-cellulose binding domain II (CBM6) of Clostridium stercorarium
      xylanase A, in order to improve its binding ability. Previous analyses using ball
      milled cellulose had suggested that a cellulose binding domain of xylanase A
      could enhance cellulase activity, especially with insoluble substrates.
      Comparison of the catalytic activities of Cel5 and Cel5-CBM6 were determined
      using carboxymethylcellulose, Avicel, and filter paper as substrates. This study
      confirmed previous findings, and provided further evidence suggesting that Cel5
      CBM6 exhibits enhanced activity with insoluble cellulose compared to native Cel5.
      However, its hydrolytic activity with soluble substrates such as
      carboxymethylcellulose was comparable to Cel5. For both cellulases, central
      linkages of cellulooligosaccharides (up to six glucose residues) were found to be
      the preferred points of cleavage. The rates of hydrolysis with both cellulases
      increased with cellulooligosaccharide chain length, and at least three
      consecutive glycosyl residues seemed to be necessary for hydrolysis to occur.
      Cel5-CBM6 showed a higher affinity for cellulose substrates than did Cel5, as
      demonstrated by transmission electron microscopy. Taken together, these results
      suggest that CBM6 increases the affinity of Cel5 for insoluble substrates, and
      this increased binding capacity seems to result in increased catalytic activity.

PMID- 14592707
TI  - Mad1p, a component of the spindle assembly checkpoint in fission yeast,
      suppresses a novel septation-defective mutant, sun1, in a cell-division cycle.
AB  - To enhance our understanding of the cytokinesis, we have carried out a genetic
      screen for temperature-sensitive Schizosaccharomyces pombe mutants that show
      defects in septum formation and cell division. Here we present the isolation and
      characterization of a new temperature-sensitive mutant, sun1 (septum
      uncontrolled), which undergoes uncontrolled septation during cell-division cycle
      at restrictive temperature (37 degrees C). In sun1 mutant, the actin ring and
      septum are positioned at random locations and angles, and the nuclear division
      cycle continues. These observations suggest that the sun1 gene product is
      required for the proper placement of the actin ring as well as precise septation.
      In a screen for the sun1(+) gene to complement the sun1 mutant, we have isolated
      a mad1(+) (mitotic arrest deficient) gene, which encodes a component of the
      spindle checkpoint in the cell-division cycle. Analysis of crossing the sun1 cell
      with the mad1(+) null mutant indicates that mad1(+) suppresses the sun1 mutant
      defective in controlled septation in a cell-division cycle.

PMID- 14592709
TI  - The hydE gene is essential for the formation of Wolinella succinogenes NiFe
      hydrogenase.
AB  - Wolinella succinogenes grows by anaerobic respiration using hydrogen gas as
      electron donor. The hydE gene is located on the genome downstream of the
      structural genes encoding the membrane-bound NiFe-hydrogenase complex (HydABC)
      and a putative protease (HydD) possibly involved in hydrogenase maturation.
      Homologs of hydE are found in the vicinity of NiFe-hydrogenase-encoding genes on
      the genomes of several other proteobacteria. A hydE deletion mutant of W.
      succinogenes does not catalyze hydrogen oxidation with various electron
      acceptors. The hydrogenase iron-sulfur subunit HydA is absent in mutant cells
      whereas the apparently processed NiFe subunit (HydB) is located exclusively in
      the soluble cell fraction. It is suggested that HydE is involved in the
      maturation and/or stability of HydA or the HydAB complex in some, but not all
      bacteria containing NiFe-hydrogenases.

PMID- 14592708
TI  - Mosquito larvicidal activity of transgenic Anabaena PCC 7120 expressing toxin
      genes from Bacillus thuringiensis subsp. israelensis.
AB  - Genes encoding the mosquito larvicidal toxins Cry4Aa, Cry11Aa, Cyt1Aa and the
      regulatory P20 from Bacillus thuringiensis subsp. israelensis were introduced
      into the nitrogen-fixing, filamentous cyanobacterium Anabaena PCC 7120 for
      expression under control of two strong promoters P(psbA) and P(A1). The clone
      pRVE4-ADRC displayed toxicity against fourth-instar larvae of Aedes aegypti, the
      highest ever achieved in cyanobacteria. It was about 2.5-fold more toxic than the
      respective clone without cyt1Aa [Wu et al., Appl. Environ. Microbiol. 63 (1997)
      4971-4975]. Cyt1Aa synergized the combination of Crys by about five-fold.
      Consistently, the lethal times exerted by pRVE4-ADRC were also reduced (it killed
      exposed larvae more quickly). This clone may become a useful biological control
      agent which reduces the probability of resistance development in the target
      organisms [Wirth et al., Proc. Natl. Acad. Sci. USA 94 (1997) 10536-10540].

PMID- 14592710
TI  - Nitrogen status modulates the expression of RNA-binding proteins in
      cyanobacteria.
AB  - Biochemical responses to cold and osmotic stresses overlap because each decreases
      the availability of free water. Since RNA-binding proteins are known to
      accumulate following cold stress and play key roles in regulating transcription
      termination, the effect of osmotic stress on expression of RNA-binding proteins
      was examined. The transcript levels of four genes encoding RNA-binding proteins
      (rbpA, rbpB, rbpC and rbpD) were monitored in Anabaena sp. PCC 7120 cultures
      supplemented with ammonium ions or growing under nitrogen-fixing conditions.
      Steady-state transcript levels of all four genes increased transiently in
      response to a temperature shift from 30 to 20 degrees C under both nitrogen
      regimes. Osmotic stress also enhanced rbpB, rbpC and rbpD gene expression in
      ammonium grown cultures. In the absence of a combined nitrogen source, osmotic
      stress repressed the short-term induction of rbp gene expression. The
      accumulation of RNA-binding proteins did not follow transcript levels, but
      remained high 24 h after stress initiation. It is concluded that nitrogen
      nutrition modulates the stress-responsive regulation of RNA-binding proteins in
      cyanobacteria, providing a potential mechanism to integrate environmental and
      developmental signals.

PMID- 14592711
TI  - Delivery of a heterologous antigen by a registered Salmonella vaccine (STM1).
AB  - STM1 is an aro A(-) attenuated mutant of Salmonella enterica serovar Typhimurium,
      and is a well-characterised vaccine strain available to the livestock industry
      for the prevention of salmonellosis in chickens. This strain has potential for
      heterologous antigen delivery, and here we show that the strain can be used to
      deliver a model antigen, ovalbumin, to immune cells in vitro and in vivo. Two
      plasmid constructs expressing the ovalbumin gene were utilised, one of which uses
      a prokaryotic promoter and the other the CMV promoter (DNA vaccine). In vitro,
      STM1 carrying ovalbumin-encoding plasmids was able to invade dendritic cells and
      stimulate a CD8(+) cell line specific for the dominant ovalbumin epitope,
      SIINFEKL. In vivo, spleen cells were responsive to SIINFEKL after vaccination of
      mice with ovalbumin-encoding plasmids in STM1, and finally, humoral responses,
      including IgA, were induced after vaccination.

PMID- 14592712
TI  - Aerobic tryptophan degradation pathway in bacteria: novel kynurenine formamidase.
AB  - While a variety of chemical transformations related to the aerobic degradation of
      L-tryptophan (kynurenine pathway), and most of the genes and corresponding
      enzymes involved therein have been predominantly characterized in eukaryotes,
      relatively little was known about this pathway in bacteria. Using genome
      comparative analysis techniques we have predicted the existence of the three-step
      pathway of aerobic L-tryptophan degradation to anthranilate (anthranilate
      pathway) in several bacteria. Based on the chromosomal gene clustering analysis,
      we have identified a previously unknown gene encoding for kynurenine formamidase
      (EC 3.5.1.19) involved with the second step of the anthranilate pathway. This
      functional prediction was experimentally verified by cloning, expression and
      enzymatic characterization of recombinant kynurenine formamidase orthologs from
      Bacillus cereus, Pseudomonas aeruginosa and Ralstonia metallidurans. Experimental
      verification of the inferred anthranilate pathway was achieved by functional
      expression in Escherichia coli of the R. metallidurans putative kynBAU operon
      encoding three required enzymes: tryptophan 2,3-dioxygenase (gene kynA),
      kynurenine formamidase (gene kynB), and kynureninase (gene kynU). Our data
      provide the first experimental evidence of the connection between these genes
      (only one of which, kynU, was previously characterized) and L-tryptophan aerobic
      degradation pathway in bacteria.

PMID- 14592713
TI  - Heterologous gene expression in Lactococcus lactis; expression of the Azotobacter
      vinelandii algE6 gene product displaying mannuronan C-5 epimerase activity.
AB  - The Azotobacter vinelandii mannuronan C-5 epimerases AlgE1-7 can be used to
      improve the properties of the commercially important polysaccharide alginate that
      is widely used in a variety of products, such as food and pharmaceuticals. Since
      lactic acid bacteria are generally regarded as safe, they are attractive
      candidates for production of the epimerases. A. vinelandii genes are GC-rich, in
      contrast to those of lactic acid bacteria, but we show here that significant
      expression levels of the epimerase AlgE6 can be obtained in Lactococcus lactis
      using the nisin-controlled expression system. A 1200-fold induction ratio was
      obtained resulting in an epimerase activity of 23900 dpm mg(-1) h(-1), using a
      tritiated alginate substrate. The epimerase was detected by Western blotting and
      nuclear magnetic resonance spectroscopy analysis of its reaction product showed
      that the enzyme displayed catalytic properties similar to those produced in
      Escherichia coli.

PMID- 14592714
TI  - Calcium restores prepenetration morphogenesis abolished by polyamines in
      Colletotrichum gloeosporioides infecting red pepper.
AB  - Colletotrichum gloeosporioides forms a specialized infection structure, an
      appressorium, to infect its host, red pepper. Polyamines (putrescine, spermidine,
      and spermine) as well as S-adenosyl methionine inhibitor, methylglyoxal-bis
      guanyl hydrazone (MGBG), impaired conidial germination and appressorium formation
      of C. gloeosporioides. Curtailment of cell differentiation by polyamines and MGBG
      was more evident in conidial germination than in appressorium development.
      Exogenous addition of calcium restored conidial germination and appressorium
      formation and expression of calmodulin-encoding gene (CgCaM) inhibited by
      polyamines. Taken together, proper regulation of intracellular polyamine
      concentration is indispensable for conidial germination and appressorium
      formation, and involved in Ca(2+)/calmodulin-dependent signaling pathways of C.
      gloeosporioides infecting red pepper.

PMID- 14592715
TI  - Anaplasma phagocytophilum major surface protein-2 (Msp2) forms multimeric
      complexes in the bacterial membrane.
AB  - Anaplasma phagocytophilum 44-kDa major surface protein-2 (Msp2) mediates partial
      neutrophil adhesion and interactions. Since A. phagocytophilum 44-kDa monoclonal
      antibodies also react with 160- and 100-kDa bands, a putative adhesin complex was
      studied. After separate excision/immunoprecipitation of these three bands, sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) resolved each into
      three bands again with increased 44-kDa protein under reducing conditions
      suggesting oligomerization of Msp2 44-kDa monomers. With 9 M urea, each
      separately excised band was resolved only into 44-kDa monomers with three
      different pIs. With protein cross-linking, immunoblots showed four additional
      bands and increased high molecular mass band intensity, suggesting homo- and
      hetero-polymerization with other A. phagocytophilum proteins. Recognition of Msp2
      complexes facilitates understanding of A. phagocytophilum-neutrophil adhesion.

PMID- 14592716
TI  - Prevalence of secreted autotransporter toxin gene among diffusely adhering
      Escherichia coli isolated from stools of children.
AB  - In this report, we analyzed the prevalence of the sat gene in 336 Escherichia
      coli samples collected from stools of children with and without diarrhea in
      Brazil and in 100 uropathogenic E. coli strains. The results show a high
      correlation between diffusely adhering E. coli (DAEC) and the presence of sat
      (44%) in intestinal isolates. DAEC strain FBC114 expresses a 107-kDa protein,
      which showed 98% homology with Sat.

PMID- 14592717
TI  - Repression by Fur is not the main mechanism controlling the iron-inducible isiAB
      operon in the cyanobacterium Synechocystis sp. PCC 6803.
AB  - The iron deficiency-dependent regulation of isiAB transcription in Synechocystis
      sp. PCC 6803 was analyzed by fusion of modified isiAB promoter fragments to gfp
      and in vivo quantification of Gfp fluorescence. For the putative Fur box only a
      slight repressing impact on promoter activity could be shown. In a heteroallelic
      fur mutant a corresponding incomplete repression of isiAB transcription under
      iron-replete conditions confirmed the role of Fur in isiAB regulation. However, a
      90 bp region upstream of the putative -35 box of the isiAB promoter was essential
      for full promoter activity under iron-deplete conditions. This pattern indicates
      a dual promoter regulation by both a repressing mechanism exhibited via the Fur
      system and an unknown activating mechanism.

PMID- 14592718
TI  - Isolation and characterization of periplasmic cyclic beta-glucans of Azorhizobium
      caulinodans.
AB  - Oligoglucose molecules isolated from Azorhizobium caulinodans were characterized
      by compositional analysis, Smith degradation, matrix-assisted laser
      desorption/ionization time of flight mass spectrometry, and (1)H and (13)C
      nuclear magnetic resonance analysis. A. caulinodans produced nonbranched and
      unsubstituted cyclic glucans composed solely of glucose, with the degree of
      polymerization ranging from 10 to 13. A major fraction of the periplasmic glucans
      contains 11 glucose residues within rings. The glucose residues are linked by
      beta-(1,3) and beta-(1,6) glycosidic bonds. These molecules seem to be quite
      similar to the periplasmic beta-(1,3);(1,6)-glucans synthesized by the
      Bradyrhizobium strain and are substantially different from the cyclic beta-(1,2)
      glucans produced by Agrobacterium and Sinorhizobium species. Azorhizobial cyclic
      glucan synthesis is not osmoregulated. The response to the osmotic stress in
      Azorhizobium can be regulated similarly to Brucella spp. It is probable that the
      biosynthesis of beta-glucans is subject to the feedback control mechanism.

PMID- 14592719
TI  - PCR and RAPD identification of L. plantarum strains isolated from ovine milk and
      cheese. Geographical distribution of strains.
AB  - Lactobacilli, and specifically Lactobacillus plantarum, are an important group of
      microorganisms in ovine cheeses, even though they are not ordinarily included in
      the starter cultures added. The present study effected counts of lactobacilli in
      Roncal Protected Designation of Origin (PDO) milk and cheese samples and isolated
      a total of 1026 strains. The strains were identified to species level by
      polymerase chain reaction (PCR) using L. plantarum-specific oligonucleotide
      primers, and the strains belonging to this species were then characterized by
      randomly amplified polymorphic DNA (RAPD). The percentage of L. plantarum present
      in the cheeses depended on the plant where the cheese was manufactured. Cluster
      analysis of the RAPD profiles obtained revealed seven main clusters. On comparing
      the strains, most of the strains present in the cheese were found not to have
      come from the raw milk.

PMID- 14592720
TI  - Strain PM2, a novel methylotrophic fluorescent Pseudomonas sp.
AB  - A novel bacterial strain, PM2, capable of growing on methanol, was isolated in
      alkaline conditions from a soil inoculum. This bacterium was characterized at the
      physiological, biochemical and molecular level. Based on biochemical and
      molecular data strain PM2 was classified as a novel member of the group of
      fluorescent pseudomonads. Evidence for the presence of a pyrroloquinoline quinone
      (PQQ)-linked alcohol dehydrogenase in this organism is presented. Strain PM2 is,
      to our knowledge, the first example of a methylotrophic Pseudomonas to be
      characterized in detail. This novel type of metabolism in Pseudomonas broadens
      even further the metabolic versatility for which this genus is renowned.

PMID- 14592721
TI  - Effect of acid shock on protein expression by biofilm cells of Streptococcus
      mutans.
AB  - Streptococcus mutans is a component of the dental plaque biofilm and a major
      causal agent of dental caries. Log-phase cells of the organism are known to
      induce an acid tolerance response (ATR) at sub-lethal pH values ( approximately
      5.5) that enhances survival at lower pH values such as those encountered in
      caries lesions. In this study, we have employed a rod biofilm chemostat system to
      demonstrate that, while planktonic cells induced a strong ATR at pH 5.5, biofilm
      cells were inherently more acid resistant than such cells in spite of a
      negligible induction of an ATR. Since these results suggested that surface growth
      itself triggered an ATR in biofilm cells, we were interested in comparing the
      effects of a pH change from 7.5 to 5.5 on protein synthesis by the two cell
      types. For this, cells were pulse labeled with [(14)C]-amino acids following the
      pH change to pH 5.5, the proteins extracted and separated by two-dimensional (2D)
      electrophoresis followed by autoradiography and computer-assisted image analysis.
      A comparison between the cells incubated at pH 5.5 and the control biofilm cells
      revealed 23 novel proteins that were absent in the control cells, and 126
      proteins with an altered relative rate of synthesis. While the number of changes
      in protein expression in the biofilm cells was within the same range as for
      planktonic cells, the magnitude of their change was significantly less in biofilm
      cells, supporting the observation that acidification of biofilm cells induced a
      negligible ATR. Mass spectrometry and computer-assisted protein sequence analysis
      revealed that ATR induction of the planktonic cells resulted in the
      downregulation of glycolytic enzymes presumably to limit cellular damage by the
      acidification of the external environment. On the other hand, the glycolytic
      enzymes in control biofilm cells were significantly less downregulated and key
      enzymes, such as lactate dehydrogenase were upregulated during pH 5.5 incubation,
      suggesting that the enhanced acid resistance of biofilm cells is associated with
      the maintenance of pH homeostasis by H+ extrusion via membrane ATPase and
      increased lactate efflux.

PMID- 14592722
TI  - Identification of a triad of arginine residues in the active site of the ArsC
      arsenate reductase of plasmid R773.
AB  - ArsC from plasmid R773 catalyzes reduction of arsenate in Escherichia coli. Arg
      60, Arg-94 and Arg-107 are near the active site residue Cys-12, suggesting that
      they form an anion binding pocket in the active site and/or participate in
      catalysis. These three arginine residues were altered to a variety of other
      residues by site-directed mutagenesis. Only mutants with arginine-to-lysine
      substitutions conferred arsenate resistance in vivo, although purified R60A,
      R60E, R60K exhibited varying levels of enzymatic activity. The data support the
      hypothesis that this triad of arginine residues is involved in arsenate binding
      and transition-state stabilization.

PMID- 14592723
TI  - L-selectin and E-selectin expressed on monocytes mediating Ehrlichia chaffeensis
      attachment onto host cells.
AB  - Ehrlichia chaffeensis, the agent of human monocytic ehrlichiosis, is an
      obligatory intracellular bacterium that exhibits monocytic host cell tropism.
      Ehrlichiae must enter the host cell, and then establish infection. The tropism of
      E. chaffeensis for monocytes suggests that the cell contains some specific
      surface components that mediate E. chaffeensis attachment and entry into host
      cells. In this study, host cell surface components that play a role in ehrlichial
      attachment were identified using a human monocyte/macrophage cell line, THP-1. E.
      chaffeensis attachment to THP-1 cells was partially blocked in the presence of
      antibodies to E-selectin and L-selectin, but not by antibodies to P-selectin,
      integrin alpham, integrin alphax, or normal mouse IgG as determined by real time
      polymerase chain reaction. Conversely, in HeLa cells that do not exhibit surface
      expression of E-selectin and L-selectin, antibodies to these cell surface
      proteins did not inhibit E. chaffeensis attachment. These findings indicate that
      E-selectin and L-selectin are cell surface proteins that might act as co
      receptors and contribute to E. chaffeensis attachment and entry into THP-1.

PMID- 14592724
TI  - New use of broomcorn millets for production of granular cultures of aphid
      pathogenic fungus Pandora neoaphidis for high sporulation potential and
      infectivity to Myzus persicae.
AB  - Glutinous broomcorn millets from the crop Panicum miliaceum were first used as
      substrate to produce granular cultures of Pandora neoaphidis, an obligate fungal
      pathogen specific to aphids. Carrying a water content of 36.5% after being
      steamed in a regular autoclaving procedure, millet grains of each 15 g (dry
      weight) in a 100-ml flask were mixed with 3 ml modified Sabouraud dextrose broth
      containing half a mashed colony of P. neoaphidis grown on egg yolk milk agar and
      then incubated at 20 degrees C and a light/dark cycle of 12 h/12 h for 21 days.
      Based on individually monitoring conidial production potential of 20 millet
      grains sampled from an arbitrarily taken flask at 3-day intervals, the millet
      cultures incubated for 6-15 days were capable of producing 16.8-23.4 x 10(4)
      conidia per millet grain with conidial ejection lasting for up to 6 days. The
      cultured millet grains individually produced significantly more conidia than
      apterous adults of Myzus persicae killed by P. neoaphidis (8.4 x 10(4) conidia
      per cadaver) and sporulated twice longer. The modeling of time-dose-mortality
      data from bioassays on M. persicae apterae exposed to conidial showers from the
      cultured millet grains and the mycelial mats produced in liquid culture resulted
      in similar estimates of LC(50) (millets: 21.4, 7.3, and 4.9 conidia mm(-2) on
      days 5-7 after exposure; mycelial mats: 22.1, 10.6, and 7.7 conidia mm(-2))
      although the LT(50) estimated at a given conidial concentration was slightly
      smaller for the millet cultures than for the mycelial mats. This indicates that
      the millet grains cultured with P. neoaphidis produced conidia as infective as or
      slightly more infective to M. persicae than those from the mycelial mats. Based
      on the sporulation potential, infectivity, and ease and cost of the millet
      cultures, the method developed in this study highly improved in vitro cultures of
      P. neoaphidis and may adapt to culturing other entomophthoralean fungi for
      microbial control of insect pests.

PMID- 14592725
TI  - Allergen-specific IgG and IgA in serum and bronchoalveolar lavage fluid in a
      model of experimental feline asthma.
AB  - Allergic asthma, a Th2 cell driven response to inhaled allergens, has classically
      been thought of as predominantly mediated by IgE antibodies. To investigate the
      role of other immunoglobulin classes (e.g., IgG and IgA) in the
      immunopathogenesis of allergic asthma, levels of these allergen-specific
      immunoglobulins were measured in serum and mucosal fluids. Bermuda grass allergen
      (BGA)-specific IgG and IgA ELISAs in serum and bronchoalveolar lavage fluid
      (BALF) were developed and optimized in an experimental model of BGA-induced
      feline asthma. Levels of BGA-specific IgG and IgA significantly increased over
      time in serum and BALF after allergen sensitization. Additionally, these elevated
      levels of BGA-specific IgG and IgA were seen in conjunction with the development
      of an asthmatic phenotype indicated by positive intradermal skin tests, enhanced
      airways hyperreactivity, and increased eosinophil percentages in the BALF.

PMID- 14592727
TI  - Shifts in circulating lymphocyte subsets in cats with feline infectious
      peritonitis (FIP): pathogenic role and diagnostic relevance.
AB  - Cats with feline infectious peritonitis (FIP) are usually lymphopenic and have
      lymphoid depletion evident in spleen and lymph nodes. In particular, the number
      of CD4+ lymphocytes in tissues decreases during the evolution of FIP lesions.
      This decrease is most likely due to increased lymphocyte apoptotic rate. In
      contrast, cats infected with the Feline Coronavirus (FCoV) develop a follicular
      hyperplasia in the peripheral lymph nodes. The current study was devised to
      evaluate the possible pathogenic role of shifts in circulating lymphocyte subsets
      in FIP. Peripheral blood from cats with FIP was evaluated and compared with
      peripheral blood from clinically healthy cats living in both FCoV-free and FCoV
      endemic catteries. Blood from cats with diseases other than FIP was also examined
      in order to define the diagnostic relevance of the changes. Lymphocyte subsets
      were analysed by flow cytometry, using a whole blood indirect immunofluorescence
      technique and mAbs specific for feline CD5, CD4, CD8, CD21. The results of the
      current study suggest that cats recently infected with FCoV that do not develop
      the disease have a transient increase in T cells; cats from groups with high
      prevalence of FIP have a moderate but persistent decrease in T cell subsets; cats
      with FIP have a very severe decrease in all the subsets of lymphocytes. Moreover,
      during FIP many lymphocytes do not express any membrane antigen, most likely due
      to early apoptosis. Cats with diseases other than FIP also had decreased number
      of lymphocytes: as a consequence, the diagnostic relevance of these findings is
      very low. Nevertheless, the lack of flow cytometric changes had a high negative
      predictive value (NPV), thus allowing to exclude FIP from the list of possible
      diagnoses in cats with normal cytograms.

PMID- 14592726
TI  - Experimental Corynebacterium pseudotuberculosis primary infection in goats:
      kinetics of IgG and interferon-gamma production, IgG avidity and antigen
      recognition by Western blotting.
AB  - Corynebacterium pseudotuberculosis is the cause of caseous lymphadenitis (CLA) in
      small ruminants, a chronic granulomatous disease that provokes significant
      zootechnics losses to ovine and goat breeders in northern Brazil. The present
      work was conducted to analyse aspects of humoral and cellular immune responses
      after experimental infection. Eight goats were infected intradermally with a
      single dose of virulent C. pseudotuberculosis strain and specific IgG, interferon
      gamma (IFN-gamma) production as well as IgG avidity and antigens pattern
      recognition dynamics against an excreted-secreted antigen were recorded during 20
      weeks. At the end of the follow-up, animals were slaughtered and necropsied.
      Although no animals showed apparent clinical signs of infection at the end of the
      trial, IFN-gamma response, even more so than the humoral response, differentiated
      animals into two groups of high or medium/low response. The time-course of IFN
      gamma production presented a short-lived primary response on day 5 after
      infection of animals of both groups, and a strong and long lasting secondary
      response starting on day 16 after infection in the high response group. The
      indirect ELISA used was able to detect a positive antibody titre between 6 and 11
      days after infection in the two groups. IgG avidity index oscillated initially
      between 15 and 45%, and showed approximately 5% units increment during the 20
      follow-up weeks. With only one individual exception, the qualitative antigens
      pattern recognition showed on day 11 after infection remained constant through
      the experiment. IgG avidity is highly correlated with IgG production, but could
      not be related with specific immunodominant bands. Both humoral and cellular
      responses kinetics presented a similar pattern of activation/deactivation but
      necropsy results suggested that the IFN-gamma test would be a very specific
      marker of CLA status.

PMID- 14592728
TI  - Production of polyclonal antisera against feline immunoglobulin E and its use in
      an ELISA in cats with experimentally induced asthma.
AB  - Serum samples from six cats with experimentally induced asthma were used to
      purify feline IgE using gel filtration and affinity chromatography. The resultant
      IgE, evaluated for purity by immunoelectrophoresis (IEP) and reactivity by
      Prausnitz-Kustner (PK) testing, was used to develop polyclonal rabbit anti-feline
      IgE antisera. Using reverse cutaneous anaphylaxis (RCA), the antisera were
      determined to be specific for feline IgE. The polyclonal rabbit anti-feline IgE
      antiserum was then validated in an allergen-specific ELISA. Serum samples from an
      additional five asthmatic cats sensitized with Bermuda grass allergen (BGA) were
      evaluated prior to sensitization, after parenteral sensitization, and after
      aerosol sensitization and challenge. A significant increase in serum BGA-specific
      IgE was noted over time.

PMID- 14592729
TI  - Full-length cDNA cloning of Toll-like receptor 4 in dogs and cats.
AB  - In the present study, full length of canine and feline Toll-like receptor 4
      (TLR4) cDNAs were sequenced, and the expression of canine and feline TLR4 mRNAs
      in dog and cat tissues were investigated. The full-length cDNA of TLR4 of dog and
      cat was 2709 bp encoding 637 amino acids and 3113 bp encoding 833 amino acids,
      respectively. The similarity of canine and feline TLR4 were 83.6% at the
      nucleotide sequence level and 77.6% at the amino acid sequence level. At the
      amino acid sequence level, canine and feline TLR4 showed sequence similarities of
      approximately 62-78% with those of Homo sapiens, Mus musculus, Bos taurus and
      Equus caballus, respectively. Southern hybridization analyses with TLR4 cDNA
      probes gave one distinct band in BamHI, EcoRI and HindIII digests of genomic DNA
      from dogs and cats, respectively, indicating the likely presence of a single TLR4
      gene in each species. By RT-PCR analysis, mRNA of canine TLR4 was expressed
      highly in peripheral blood leukocytes (PBL), moderately in spleen, stomach and
      small intestine, at low levels in liver, with no expression in kidney, large
      intestine and skin. On the other hand, mRNA of feline TLR4 was expressed highly
      in lung, bladder and PBL, moderately in kidney, liver, spleen and large intestine
      and at low levels in pancreas and small intestine.

PMID- 14592730
TI  - Characterization of platelet and soluble-porcine P-selectin (CD62P).
AB  - P-selectin (CD62P), an adhesion molecule expressed on activated endothelial cells
      and platelets, mediates the initial attachment of leukocytes to the stimulated
      endothelium upon inflammation and the interaction between leukocytes and
      platelets. A soluble form of P-selectin is present in the serum of healthy
      individuals as a circulating protein and high levels have been described in
      various pathological situations. The aim of this study was to characterize P
      selectin on porcine platelets and investigate the soluble form of this protein,
      which are uncharacterized in several animal species including pigs. A new
      monoclonal antibody (mAb) (SwPsel.1.9) against porcine P-selectin was produced
      using a mouse cell line transfected with pig P-selectin cDNA. This mAb together
      with a previously described mAb (P-sel.KO.2.5), produced in our laboratory, was
      used to develop an ELISA to quantify porcine P-selectin. No significant levels of
      soluble-porcine P-selectin were observed in healthy animals. However, the total
      amount of P-selectin measured in porcine platelets was similar to that found in
      humans. Increased levels of this circulating protein were detected in the plasma
      from pigs after allograft implantation. In vitro, P-selectin expression on
      platelet membrane was rapidly induced by PMA and thrombin, as assessed by flow
      cytometry. However, these activators did not stimulate the release of soluble P
      selectin. Analysis of the proteolytic cleavage of this protein from COS
      transfected cells revealed that PMA treatment failed to cause the shedding of
      membrane-bound P-selectin. These data suggest that porcine P-selectin is a
      suitable marker for inflammation and that the mechanism involved in the
      generation of circulating P-selectin is not proteolytic release.

PMID- 14592731
TI  - Immunostimulant properties of a cell wall-modified whole Saccharomyces cerevisiae
      strain administered by diet to seabream (Sparus aurata L.).
AB  - The possible differences in the immunostimulant effects between whole wild
      Saccharomyces cerevisiae and a mutant strain (fks-1) administered in the diet to
      gilthead seabream (Sparus aurata L.) were studied. Fish were fed diets containing
      0 (control) or 10 g whole wild yeast or fks-1 strain per kilogram feed for 2, 4
      or 6 weeks. After each sampling, the innate humoral (complement, lysozyme and
      peroxidases) and cellular (intracellular peroxidases, phagocytosis, respiratory
      burst activity and cytotoxicity) responses were determined. Among the humoral
      responses, serum peroxidases and complement activity were significantly decreased
      after 6 weeks of feeding with the fks-1 strain-supplemented diet, while lysozyme
      activity increased after 2 and 4 weeks of feeding the fks-1 strain. Of the
      cellular responses studied, phagocytosis was increased to a significant degree at
      all the assayed times but only by the fks-1 strain-supplemented diet, while
      respiratory burst activity (after 4 weeks) and natural cytotoxicity (after 4 and
      6 weeks) increased with either yeast strain. The intracellular peroxidase content
      was not affected by the dietary supplementation of either yeast strain. These
      results are discussed with a view to assessing the possible use of wild and/or
      mutant yeast strains for immunostimulant purposes in aquaculture.

PMID- 14592732
TI  - Dynamics of leukocytes and cytokines during experimentally induced Streptococcus
      uberis mastitis.
AB  - Streptococcus uberis causes a significant proportion of clinical and subclinical
      intramammary infections (IMI) in lactating and non-lactating dairy cows. In spite
      of this, its pathogenesis is incompletely understood. A study was conducted to
      determine leukocyte and cytokine dynamics during experimentally induced S. uberis
      mastitis. Five Jersey and five Holstein cows were challenged via intramammary
      inoculation of S. uberis into two uninfected mammary glands. Sixteen of 20
      challenged mammary glands developed clinical mastitis with peak clinical signs
      observed at 144 h. The number of S. uberis in milk increased (P<0.05) 48 h after
      challenge, in spite of an increase in milk somatic cells that began at 18 h
      (P<0.001) and remained elevated throughout the study. Increased tumor necrosis
      factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and interleukin-8 (IL-8)
      in milk were detected 66 h after challenge (P<0.05). Peak TNF-alpha and IL-8
      concentrations occurred 120 h after challenge and preceded peak clinical signs.
      Experimental S. uberis IMI induced local production of TNF-alpha, IL-1beta and IL
      8, which may play a role in the pathogenesis of S. uberis mastitis. Other
      mediators may be involved in initial leukocyte recruitment to the mammary gland,
      since increases in milk somatic cells occurred earlier than cytokine production.

PMID- 14592733
TI  - Pre-infection frequencies of equine herpesvirus-1 specific, cytotoxic T
      lymphocytes correlate with protection against abortion following experimental
      infection of pregnant mares.
AB  - In general, vaccines containing inactivated equine herpesvirus-1 (EHV-1) fail to
      prevent abortion in pregnant mares following infection with a virulent strain of
      EHV-1. We have tested the hypothesis that resistance to EHV-1-induced abortion in
      pregnant mares is associated with high frequencies of EHV-1 specific, major
      histocompatibility complex (MHC) class I-restricted, cytotoxic T lymphocytes
      (CTL) in the circulation. To test this theory, three groups of pregnant mares
      were assembled with varying backgrounds of infection or vaccination in an attempt
      to mimic the immune status of the general population. Group 1 mares (n=9) were
      untreated controls selected at random. Group 2 mares (n=5) were vaccinated three
      times intramuscularly with inactivated EHV-1. Group 3 mares (n=3) had been
      infected with EHV-1 on four previous occasions. The frequency of CTL in blood
      leucocytes was measured by limiting dilution analysis at three time points; at
      the beginning of pregnancy (approximately 28 weeks before infection) in the Group
      2 and Group 3 mares (4-7 weeks of gestation) (Group 1 was unavailable for
      sampling) and then 2 weeks before (30-40 weeks of gestation) and 3 weeks after
      experimental infection in all the mares. Serum samples were collected to monitor
      complement fixing (CF) antibody titres. Mares in all three groups were infected
      experimentally with EHV-1 strain Ab4/8 by the intranasal route after which they
      were monitored clinically to determine the outcome of pregnancy and samples were
      collected to determine the duration of nasopharyngeal shedding and cell
      associated viraemia. The untreated control mares showed low pre-infection CTL.
      After experimental infection, they all seroconverted, aborted and demonstrated
      expected clinical and virological signs. Some vaccinated mares (3/5) had elevated
      titres of CF antibody prior to their first vaccination. All the vaccinated mares
      seroconverted after vaccination and exhibited higher CTL frequencies than
      controls before infection. Four of the five foaled normally. The multiply
      infected mares had low CF antibody titres prior to infection and showed neither
      seroconversion nor clinical or virological signs after infection. All multiply
      infected mares exhibited high frequencies of CTL before infection and they all
      foaled normally. The CTL frequencies observed differed significantly from the
      expected frequencies in the control and multiply infected groups at 2 weeks pre
      infection (P=0.034) and between the foaling and aborting mares at 2 weeks pre
      infection (P=0.005) and 3 weeks post-infection (P=0.015). The results show a
      positive correlation between the number of virus-specific CTL in the peripheral
      blood of pregnant mares and their protection against abortion induced by EHV-1
      infection. Therefore, as indicated by this study, rational approaches to the
      development of new vaccines for EHV-1 should stimulate cytotoxic immune responses
      and develop virus-specific CTL as pre-requisites for protection against abortion.

PMID- 14592734
TI  - Enteric-coated pellets of F4 fimbriae for oral vaccination of suckling piglets
      against enterotoxigenic Escherichia coli infections.
AB  - To prevent enterotoxigenic Escherichia coli (ETEC) induced postweaning diarrhoea,
      the piglet needs an active mucosal immunity at the moment of weaning. In the
      present study, the feasibility of oral vaccination of suckling piglets against
      F4+ETEC infection with F4 fimbriae was studied. Furthermore, oral vaccination
      with enteric-coated pellets of F4 fimbriae was compared to vaccination with F4
      fimbriae in solution. Therefore, piglets were orally administered 1mg F4 fimbriae
      in pellets or in solution during three successive days at the age of 7 and 21
      days, whereas control piglets were not vaccinated. Five days postweaning (33 days
      of age), all animals were orally challenged with F4+ETEC. Despite the induction
      of an immune response upon oral administration of both F4 fimbriae in pellets as
      in solution, the colonisation of the small intestine by F4+ETEC upon oral
      challenge could not be prevented. However, a marginal but significant reduction
      in F4+ E. coli faecal excretion was found in the piglets vaccinated with F4
      fimbriae in pellets, indicating that the use of an enteric-coat which protects
      the F4 fimbriae against inactivation by milk factors and degradation by enzymes
      and bile improves vaccination.

PMID- 14592735
TI  - Presence of the di-leucine motif in the cytoplasmic tail of the pig FcRn alpha
      chain.
AB  - The sequence of the pig FcRn alpha chain was recently published. The lack of a
      conserved di-leucine motif in the cytoplasmic tail suggests a rare polymorphism
      in the described animal, alternatively, a sequencing error. We therefore cloned
      and sequenced the pig FcRn alpha chain. Our sequence, along with a previous NCBI
      GenBank submission and five pig derived EST clones clearly demonstrate the
      presence of di-leucine motif in the cytoplasmic tail of the pig FcRn. No
      polymorphism in the cytoplasmic tail-encoding region was found in 25 animals from
      six pig breeds based on single-stranded conformation polymorphism and sequencing
      analysis, suggesting that the previously described pig FcRn alpha chain may
      represent a sequencing error in the 3' portion of the gene.

PMID- 14592736
TI  - Immunoglobulin levels in Bull terriers suffering from lethal acrodermatitis.
AB  - An enzyme-linked immunosorbent assay, developed by one the authors (Huang, 1993)
      was used to measure immunoglobulin levels in previously stored plasma samples
      from eight dogs suffering from lethal acrodermatitis (LAD) and 10 normal Bull
      terriers. The aim of the study was to document plasma immunoglobulin levels and
      to determine if dogs suffering from LAD had low IgA levels. The results showed
      that dogs suffering from LAD had normal IgG and IgM levels but significantly
      lower IgA levels than the control group. This finding may in part explain the
      frequent occurrence of microbial infections recorded in dogs suffering from LAD.

PMID- 14592737
TI  - Down-regulation of MHC class II receptors of DH82 cells, following infection with
      Ehrlichia canis.
AB  - In order to evaluate whether infection with E. canis alters the expression of
      major histocompatibility complex (MHC) class I and/or MHC class II receptors, and
      by doing so alters the immune response to the organism, flow cytometry was
      performed on DH82 cells infected with Ehrlichia canis (90% infection) and on
      uninfected DH82 cells of the same passage, using anti-canine MHC class I and II
      antibodies. MHC class II expression was evident in 47.6 and 46.2% (mean 46.9%) of
      uninfected DH82 cells using two different anti-MHC class II antibodies, while no
      MHC class II expression was evident in DH82 cells infected with E. canis. The
      present results indicate that infection of DH82 macrophages with E. canis down
      regulates their MHC class II receptors. These results suggest a possible
      mechanism by which E. canis evades the immune system.

PMID- 14592738
TI  - Citrus waste recovery: a new environmentally friendly procedure to obtain animal
      feed.
AB  - Citrus juice centrifugation pulp is the semi-solid product obtained from the
      industrial centrifugation of juices, to obtain a clear juice. This waste causes
      many economic and environmental problems because of its fermentability. In this
      paper we describe a method which makes it possible to obtain animal feed from
      citrus juice centrifugation pulp. To this end, alkaline and/or enzymatic
      treatments were carried out on the centrifugation pulp. These treatments
      facilitate pressing and so help to produce a material which, using suitable
      methods, may be dried. Enzyme treatment proved to be the most efficient of the
      methods under investigation designed to favour the pressing of the pulp. The
      product obtained with this method showed excellent digestibility in vitro and its
      protein content, although not especially high, compared favourably with that of
      many other agroindustrial waste products currently used as components of animal
      feed.

PMID- 14592739
TI  - Shell of abalone Haliotis diversicolor supertexta can eliminate waterborne zinc
      biokinetically.
AB  - Dietary and nondietary accumulation of waterborne zinc (Zn) by shell of abalone
      Haliotis diversicolor supertexta was studied to determine if abalone shell can
      accumulate and eliminate Zn biokinetically. Shell of H. diversicolor supertexta
      rapidly accumulated Zn at microgram per gram concentrations during a 7-d uptake
      period for dietary and nondietary exposure to 1 microgml(-1) Zn seawater.
      Depuration half-lives were 7.22 and 15.40 d for dietary and nondietary exposure,
      respectively. The uptake rate constants were 5.12 and 4.84 ml g(-1)d(-1),
      respectively, for dietary and nondietary exposure. The depuration rate constants
      were 0.048 and 0.10 d(-1), respectively for dietary and nondietary exposure.
      Results from this study showed that the shell of H. diversicolor supertexta
      accumulated Zn and that it reflected the composition of the seawater in which the
      abalone lived. This suggested that the shell of H. diversicolor supertexta can be
      used as a bioindicator or can act as a receptor to biokinetically eliminate heavy
      metals from aquatic food webs.

PMID- 14592740
TI  - Microbiological changes during bioremediation of explosives-contaminated soils in
      laboratory and pilot-scale bioslurry reactors.
AB  - Changes in the microbial community during bioremediation of explosives
      contaminated soil in a molasses-fed bioslurry process were examined. Upon
      addition of molasses to laboratory-scale reactors, total culturable heterotrophs
      increased rapidly by three to four orders of magnitude. However, heat-shocked
      heterotrophs and the percentage of gram-positive bacterial isolates did not
      increase until the soluble concentrations of 2,4,6-trinitrotoluene (TNT) and
      2,4,6-trinitrobenzene (TNB) began to decrease. The number of identified
      phospholipid fatty acids (PLFA) and the total PLFA concentration also exhibited
      an immediate increase in response to molasses addition, while the concentration
      of branched PLFA, indicative of the gram-positive population, remained low until
      soluble TNT and TNB concentrations had significantly decreased. This same general
      relationship between explosives degradation and gram-positive-specific PLFA was
      observed during an experiment with a large field-scale bioslurry lagoon reactor.
      These results indicate that the gram-positive organisms, which have been shown to
      be severely impacted by even low concentrations of TNT and TNB [Current
      Microbiol. 35 (1997) 77; Environ. Toxicol. Chem. 17 (1998) 2185], are able to
      increase in concentrations after explosives compounds are reduced to non
      inhibitory levels, and should therefore be able to reestablish themselves in
      remediated soils.

PMID- 14592741
TI  - Reuse of microbially treated olive mill wastewater as fertiliser for wheat
      (Triticum durum Desf.).
AB  - Free cells of Aspergillus niger were grown on olive mill wastewater (OMW)
      supplemented with rock phosphate (RP) in an air-lift bioreactor in batch and
      repeated-batch processes. The fungus grew well and reduced the chemical oxygen
      demand of the waste by 35% and 64% in the batch and repeated-batch (fourth batch)
      processes, respectively. Total sugar content was consistently reduced (ca. 60%)
      in both processes while reduction of total phenols was minimal. RP was
      solubilised and maximum soluble P was 0.63 and 0.75 gl(-1) in the batch and
      repeated-batch (third batch), respectively. Several types of OMW+/-RP,
      microbially-treated or not, were tested in a greenhouse for their fertilising
      ability on a soil-wheat (Triticum durum Desf.) model system. Beneficial effects
      were highest using OMW treated by the repeated-batch process. The treated plants
      showed an increase in seed biomass, spike number, and kernel weight. Harvest
      index was highest (0.49+/-0.04) after treatment with OMW from the repeated-batch
      process.

PMID- 14592742
TI  - Reversal of dormancy in switchgrass with low-light photoperiod extension.
AB  - Some switchgrass (Panicum virgatum L.) cultivars originating in the northern USA
      show limited late-summer and fall growth when grown in more southerly locations
      despite adequate temperature and moisture. Our objective was to determine the
      effects of low-light photoperiod extension on the dry matter yield of switchgrass
      cultivars originating from contrasting latitudes. Seedlings of the four cultivars
      (Cave-in-Rock, 'Caddo', 'Kanlow', and 'Alamo') were grown for 100 d in a
      greenhouse in winter under ambient (11.2-12.2 h) and extended (18 h)
      photoperiods. Photoperiod extension was with 7 micromol m(-2) s(-1)
      photosynthetic photon flux density. Cultivars responded differently to
      photoperiod extension (P<0.05). Large increases in dry matter yield at extended
      photoperiods were observed in Cave-in-Rock (+98%) and Caddo (+129%). The dry
      matter yield of Kanlow increased by 31%, whereas dry matter yield of the
      southernmost cultivar Alamo was not affected by photoperiod extension. Yield
      increases for Cave-in-Rock and Caddo were associated with increased tiller number
      and weight. A reversal of dormancy for some cultivars with a photoperiodic signal
      verified that dormancy was not simply a result of a low radiant input.

PMID- 14592743
TI  - A dispersion modelling approach to determining the odour impact of intensive pig
      production units in Ireland.
AB  - It is becoming more common now to use atmospheric dispersion models to predict
      where odour nuisance is likely to occur near pig units. An odour threshold
      concentration of 1 OuE m(-3) is the level at which an odour is detectable by 50%
      of screened panellists. A new odour annoyance criterion (C(98,1-h) (98%-ile, 1-h
      average odour concentration) < or = 4.3 OuE m(-3)) was developed in this study
      and compared to the Environmental Protection Agency (EPA) (Ireland)
      recommendation (C(98,1-h)< or = 6 OuE m(-3)) using the ISCST3 model with data
      from three meteorological stations. Abatement techniques such as exhaust vent
      modification, feed manipulation, and biofiltration were assessed. Based on
      current limits (C(98,1-h)< or = 6 OuE m(-3)) for existing facilities, predicted
      setback distances can be up to 780 m for a 1000-sow unit, depending on which
      meteorological data set is used. However, if using the suggested odour impact
      criterion in this research (C(98,1-h)< or = 4.3 OuE m(-3)), setback distances
      could reach a maximum of 1000 m. Biofilters on second stage weaning and finishing
      pig buildings offer the greatest single reduction (up to 650 m) in odour impact.
      When combined with feed manipulation and increased exhaust air velocity, the
      figure can be as high as 920 m. Due to the critical requirement for local
      meteorological data, it is recommended that a meteorological station be installed
      on large pig units to facilitate more accurate predictions. Site measurements of
      odour emissions should be made in each case because emissions are influenced by a
      range of local factors including feed, manure management, building design and
      operation.

PMID- 14592744
TI  - Production of cellulases and hemicellulases by Aspergillus niger KK2 from
      lignocellulosic biomass.
AB  - To investigate the production of cellulases and hemicellulases from Aspergillus
      niger KK2, solid state fermentation (SSF) was performed by using different ratios
      of rice straw and wheat bran. When A. niger KK2 was grown on rice straw alone as
      a solid support in SSF, the maximum FPase activity was 19.5 IU g(-1) in 4 days.
      Also, CMCase (129 IU g(-1)), beta-glucosidase (100 IU g(-1)), xylanase (5070 IU
      g(-1)) and beta-xylosidase (193 IU g(-1)) activities were concurrently obtained
      after 5-6 days of fermentation. The higher enzyme activities produced by A. niger
      KK2 is a significant advantage from the viewpoint of practical saccharification
      reaction. Cellulases and hemicellulases produced by A. niger KK2 might be applied
      to pulp and paper industry, feed industry and chemical industry.

PMID- 14592745
TI  - Enzymatic grafting of carboxyl groups on to chitosan--to confer on chitosan the
      property of a cationic dye adsorbent.
AB  - Chitosan (CTS) is a good adsorbent for dyes but lacks the ability to adsorb
      cationic dyes. In this study, chitosan was modified to possess the ability to
      adsorb cationic dyes from water. Four kinds of phenol derivatives: 4
      hydroxybenzoic acid (BA), 3,4-dihydroxybenzoic acid (DBA), 3,4-dihydroxyphenyl
      acetic acid (PA), hydrocaffeic acid (CA) were used individually as substrates of
      tyrosinase to graft onto chitosan. FTIR analysis provided supporting evidence of
      phenol derivatives being grafted. The grafting amounts of these phenol
      derivatives onto chitosan were examined by the adsorption of an anionic dye
      (amaranth) and reached a plateau value. The final contents of carboxyl groups in
      chitosan (mmol carboxyl groups per kg chitosan) were measured as 46.36 for BA,
      70.32 for DBA, 106.44 for PA, and 113.15 for CA. These modified chitosans were
      used in experiments on uptake of the cationic dyes crystal violet (CV) and
      bismarck brown Y (BB) by a batch adsorption technique at pH 7 for CV and at pH 9
      for BB and 30 degrees C. Langmuir type adsorption was found, and the maximum
      adsorption capacities for both dyes were increased with the following order CTS
      CA>CTS-PA>CTS-DBA>CTS-BA.

PMID- 14592746
TI  - Evolution of organic matter from sewage sludge and garden trimming during
      composting.
AB  - To use compost appropriately in agriculture it is extremely important to estimate
      the stabilization level of the organic matter. In this work, two different piles
      of compost were studied by means of (i) humification parameters (degree of
      humification--DH, humification rate--HR, humification index--HI) prior to and
      after enzymatic hydrolysis of the extracted organic carbon, (ii) water-soluble
      organic carbon (WSOC) and (iii) water-soluble nitrogen. A significant
      relationship between composting time, WSOC and humification parameters after
      enzymatic hydrolysis (DHenz; HRenz; HIenz) was found.

PMID- 14592747
TI  - Effect of turning regime and seasonal weather conditions on nitrogen and
      phosphorus losses during aerobic composting of cattle manure.
AB  - Cattle manure from stock bedded on straw was aerobically composted under ambient
      conditions, turning with either a tractor-mounted front-end loader or a rear
      discharge manure spreader. Three composting experiments, each of approximately
      four months duration, were conducted to investigate the effect of turning regime
      and seasonal weather conditions on nitrogen and phosphorus losses during aerobic
      composting of cattle manure. Manure stacks of 12-15 m(3) initial volume were
      constructed in separate 5 x 5 m concrete compartments. Experiment 1 (January
      April 1999) compared manure heaps turned once (T1) or three times (T3) using a
      front-end loader with an unturned static (S) control manure stack. Experiment 2
      (June-September 1999) compared the same treatments as Experiment 1. Experiment 3
      (September-December 1999) compared T1 and T3 turning regimes using a front end
      loader with turning by a rear-discharge spreader (TR1 and TR1T2) for more
      effective aeration of the manure. Turning took place at 6 weeks for the one turn
      treatments, and after 2, 6 and 10 weeks for the three turn treatments. Leachate
      losses were dominated by NH(4)-N during the first three weeks of composting,
      after which time NH4-N and NO3-N concentrations in leachates were approximately
      the same, in the range 0-20 mg N l(-1). The concentrations of both NH4-N and NO3
      N in leachate were higher after turning. Molybdate-reactive P concentrations in
      leachate tended not to be significantly influenced by turning regime. Gaseous
      losses of NH3 and N2O rose quickly during the initial phases of composting,
      peaking at 152 g N t(-1) d(-1) for the T3 treatment. Mean NH3 emission rate (25
      252 g N t(-1) d(-1)) for the first two weeks of Experiment 2 conducted during the
      period June-September were an order of magnitude greater (1-10 g N t(-1) d(-1))
      than Experiment 3, conducted during the colder, wetter autumn period (September
      December). Nitrous oxide emission rates ranged between 1-14 g N t(-1) d(-1) and
      showed little influence of turning regime. Total N and P concentrations in turned
      (T) and static (S) manure were elevated at the end of all experiments, due to
      loss of dry matter. Mean total N losses were 30.4% (T1) and 36.8% (T3) and total
      P losses 28.2% (T1) and 27.4% (T3).

PMID- 14592748
TI  - A bioethanol process development unit: initial operating experiences and results
      with a corn fiber feedstock.
AB  - Interest in bioethanol production from lignocellulosic feedstocks for use as an
      alternative fuel is increasing, but near-term commercialization will require a
      low cost feedstock. One such feedstock, corn fiber, was tested in the US
      Department of Energy (DOE)/National Renewable Energy Laboratory (NREL) bioethanol
      pilot plant for the purpose of testing integrated equipment operation and
      generating performance data. During initial runs in 1995, the plant was operated
      for two runs lasting 10 and 15 days each and utilized unit operations for
      feedstock handling, pretreatment by dilute sulfuric-acid hydrolysis, yeast
      inoculum production, and simultaneous saccharification and fermentation using a
      commercially available cellulase enzyme. Although significant operational
      problems were encountered, as would be expected with the startup of any new
      plant, operating experience was gained and preliminary data were generated on
      corn fiber pretreatment and subsequent fermentation of the pretreated material.
      Bacterial contamination was a significant problem during these fermentations.

PMID- 14592749
TI  - Optimization of initial substrate and pH levels for germination of sporing
      hydrogen-producing anaerobes in cow dung compost.
AB  - Biohydrogen production by anaerobic microbes enriched from heat-shocked cow dung
      compost was studied by using an artificial medium containing sucrose. Initial pH
      and substrate levels were selected as target factors in this study. Our
      experimental results demonstrated that optimal substrate concentration and pH for
      the composts generating hydrogen gas were 4.0+/-0.5 g sucrose/l and 5.4+/-0.2,
      respectively. Supplementary experiments confirmed that chemical oxygen demand
      reduction efficiency (69%) obtained from the conditions of sucrose=4.0 g/l and
      pH=5.5 was significantly greater than that (37%) from sucrose=5.0 g/l and pH=5.0.
      Experimental results of metabolites analysis led us to the conclusion that
      Clostridium sp. predominated in the anaerobic composts, suggesting that inocula
      used to seed the batch experiment can be obtained from a common natural source.

PMID- 14592750
TI  - Agrochemical characterisation of "alperujo", a solid by-product of the two-phase
      centrifugation method for olive oil extraction.
AB  - Introduction of the two-phase centrifugation system for olive oil extraction
      during the early nineties in Spain has led to the generation of approximately
      four million tons per year of a solid olive-mill by-product called "alperujo"
      (AL). Agrochemical characterisation showed that AL has a high moisture content,
      slightly acidic pH values and a very high content of organic matter, mainly
      composed by lignin, hemicellulose and cellulose. It also has a considerable
      proportion of fats, proteins, water-soluble carbohydrates and a small but active
      fraction of hydrosoluble phenolic substances. Amongst plant nutrients, AL is rich
      in potassium, less so in (mainly organic) nitrogen and poor in phosphorus and
      micronutrients. Some of those properties are not compatible with agricultural
      requirements, for which reason composting may be considered a suitable
      alternative for its disposal. AL needs to be characterised before composting, and
      so an attempt was made to correlate the easily determined ash content with other
      parameters; the regression models thus obtained are discussed.

PMID- 14592751
TI  - Thermal-alkaline solubilization of waste activated sludge as a pre-treatment
      stage for anaerobic digestion.
AB  - This work studied the hydrolysis kinetics and the solubilization of waste
      activated sludge under a medium range temperature (50-90 degrees C) and pH in the
      alkaline region (8-11), as a pretreatment stage for anaerobic digestion. The
      hydrolysis rate for the solubilization of volatile suspended solids (VSS)
      followed a first-order rate. A linear polynomial hydrolysis model was derived
      from the experimental results leading to a satisfactory correlation between the
      hydrolysis rate coefficient, pH, and temperature. At pH 11 and a temperature of
      90 degrees C the concentration of the VSS was 6.82%, the VSS reduction reached
      45% within ten hours and at the same time the soluble COD was 70.000 mg/l and the
      total efficiency for methane production 0.28 l of CH4 per g of VSS loading.

PMID- 14592752
TI  - Assessing the feasibility of achieving biological nutrient removal from
      wastewater at an Irish food processing factory.
AB  - In Ireland, wastewaters emanating from the food industry typically contain
      elevated levels of nitrogen and phosphorus before treatment. Two pilot scale
      studies were performed to determine the feasibility of achieving biological N and
      P removal on-site at a food ingredients plant. The wastewater treated by the
      pilot reactors was that which resulted from the day-to-day production in the full
      scale food ingredients plant. Both reactors were of the anaerobic/anoxic/oxic
      (A/A/O) design, however the sizing of the zones was varied in this study. In the
      first pilot study, while treating a wastewater of the following strength: 1008 mg
      COD/l; 30.1 mg NH4-N/l and 26.7 mg P/l, removal efficiencies of 93%, 99% and 98%
      were obtained for COD, NH4-N and P, respectively. In the second study, while
      operating at reduced hydraulic retention times and lower recycle rates, the pilot
      plant treated a wastewater of the following strength: 1757 mg COD/l; 62 mg NH4
      N/l and 57 mg P/l, with removal efficiencies of 94%, 97% and 75% obtained for
      COD, NH4-N and P, respectively. This work showed that biological nutrient removal
      could be successfully applied to treatment of food industry wastewaters.

PMID- 14592753
TI  - Energy evaluation of forest residues originated from shrub species in Galicia.
AB  - In this study we present an alternative for the management of the excess of shrub
      species that nowadays take up around 800000 ha in Galicia (NW Spain). This
      alternative is based on the exploitation of the energetic resources contained in
      the excess of shrubs by their combustion in specially designed plants for
      production of electric energy. The different species were sorted into three
      groups: Ulex europaeus L. (furze), Sarothamnus scoparius (L.) Link (broom) and
      Erica sp. (heaths). Their LHV were calculated through measurements of the
      corresponding HHV and resulted 7600, 7300 and 7200 kJ kg(-1) respectively.
      Biomass productions (T ha(-1)) were also calculated resulting 20 T ha(-1)
      (furze), 30 T ha(-1) (broom), and 15 T ha(-1) (heaths). Analyses of all these
      values make these species very valuable for their energy exploitation. Samples
      were collected over one year in different zones to study the effect of the
      environmental conditions on the calorific values.

PMID- 14592754
TI  - Genetic diversity between human metapneumovirus subgroups.
AB  - Complete consensus nucleotide sequences were determined for human metapneumovirus
      (HMPV) isolates CAN97-83 and CAN98-75, representing the two proposed genotypes or
      genetic subgroups of HMPV. The overall level of genome nucleotide sequence
      identity and aggregate proteome amino acid sequence identity between the two HMPV
      subgroups were 80 and 90%, respectively, similar to the respective values of 81
      and 88% between the two antigenic subgroups of human respiratory syncytial virus
      (HRSV). The diversity between HMPV subgroups was greatest for the SH and G
      proteins (59 and 37% identity, respectively), which were even more divergent than
      their HRSV counterparts (72 and 55% cross-subgroup identity, respectively). It is
      reasonable to anticipate that the two genetic subgroups of HMPV represent
      antigenic subgroups approximately comparable to those of HRSV.

PMID- 14592755
TI  - Genetic and phylogenetic characterization of the type II cyclobutane pyrimidine
      dimer photolyases encoded by Leporipoxviruses.
AB  - Shope fibroma virus and myxoma virus encode proteins predicted to be Type II
      photolyases. These are enzymes that catalyze light-dependent repair of
      cyclobutane pyrimidine dimers (CPDs). When the Shope fibroma virus S127L gene was
      expressed in an Escherichia coli strain lacking functional CPD repair pathways,
      the expressed gene protected the bacteria from 70-75% of the ultraviolet (UV)
      light-induced cytotoxic DNA damage. This proportion suggests that Leporipoxvirus
      photolyases can only repair CPDs, which typically comprise approximately 70% of
      the damage caused by short wavelength UV light. To test whether these enzymes can
      protect virus genomes from UV, we exposed virus suspensions to UV-C light
      followed by graded exposure to filtered visible light. Viruses encoding a
      deletion of the putative photolyase gene were unable to photoreactivate UV damage
      while this treatment again eliminated 70-90% of the lethal photoproducts in wild
      type viruses. Western blotting detected photolyase protein in extracts prepared
      from purified virions and it can be deduced that the poxvirion interior must be
      fluid enough to permit diffusion of this approximately 50-kDa DNA-binding protein
      to the sites where it catalyzes photoreactivation. Photolyase promoters are
      difficult to categorize using bioinformatics methods, as they do not obviously
      resemble any of the known poxvirus promoter motifs. By fusing the SFV promoter to
      DNA encoding a luciferase open reading frame, the photolyase promoter was found
      to exhibit very weak late promoter activity. These data show that the genomes of
      Leporipoxviruses, similar to that of fowlpox virus, encode catalytically active
      photolyases. Phylogenetic studies also confirmed the monophyletic origin of
      poxviruses and suggest an ancient origin for these genes and perhaps poxviruses.

PMID- 14592756
TI  - Vacuolating encephalitis in mice infected by human coronavirus OC43.
AB  - Involvement of viruses in human neurodegenerative diseases and the underlying
      pathologic mechanisms remain generally unclear. Human respiratory coronaviruses
      (HCoV) can infect neural cells, persist in human brain, and activate myelin
      reactive T cells. As a means of understanding the human infection, we
      characterized in vivo the neurotropic and neuroinvasive properties of HCoV-OC43
      through the development of an experimental animal model. Virus inoculation of 21
      day postnatal C57BL/6 and BALB/c mice led to a generalized infection of the whole
      CNS, demonstrating HCoV-OC43 neuroinvasiveness and neurovirulence. This acute
      infection targeted neurons, which underwent vacuolation and degeneration while
      infected regions presented strong microglial reactivity and inflammatory
      reactions. Damage to the CNS was not immunologically mediated and microglial
      reactivity was instead a consequence of direct virus-mediated neuronal injury.
      Although this acute encephalitis appears generally similar to that induced by
      murine coronaviruses, an important difference rests in the prominent spongiform
      like degeneration that could trigger neuropathology in surviving animals.

PMID- 14592757
TI  - Evidence for quasispecies distributions in the human hepatitis A virus genome.
AB  - Nucleotide sequence analysis of multiple molecular clones of the hepatitis A
      virus (HAV), generated by reverse transcription-PCR of two capsid-coding regions,
      revealed a degree of heterogeneity compatible with a quasispecies structure in
      three clinical samples. Passage of plaque-purified reference strain HAV pHM175
      43c in FRhK-4 cells documented the generation of a mutant distribution of HAV
      genomes. The mutant spectra showed mutation frequencies in the range of 1 x 10(
      3) to 1 x 10(-4) substitutions per nucleotide, with a dominance of transition
      over transversion mutations. While in the VP3-coding region, nonsynonymous
      mutations were predominant; in the VP1-coding region they were uncommon. Around
      50% of the amino acid replacements involved residues located at or near antigenic
      sites. Most of the detected mutations occurred at or in the vicinity of rare
      codons, suggesting a dynamics of mutation-selection, predominantly at and around
      rare codons. The results indicate that despite antigenic conservation, HAV
      replicates as a complex distribution of mutants, a feature of viral quasispecies.

PMID- 14592758
TI  - Replication and interaction of herpes simplex virus and human papillomavirus in
      differentiating host epithelial tissue.
AB  - We have investigated the interactions and consequences of superinfecting and
      coreplication of human papillomavirus (HPV) and herpes simplex virus (HSV) in
      human epithelial organotypic (raft) culture tissues. In HPV-positive tissues, HSV
      infection and replication induced significant cytopathic effects (CPE), but the
      tissues were able to recover and maintain a certain degree of tissue integrity
      and architecture. HPV31b not only maintained the episomal state of its genomic
      DNA but also maintained its genomic copy number even during times of extensive
      HSV-induced CPE. E2 transcripts encoded by HPV31b were undetectable even though
      HPV31b replication was maintained in HSV- infected raft tissues. Expression of
      HPV31b oncogenes (E6 and E7) was also repressed but to a lesser degree than was
      E2 expression. The extent of CPE induced by HSV is dependent on the magnitude of
      HPV replication and gene expression at the time of HSV infection. During active
      HSV infection, HPV maintains its genomic copy number even though genes required
      for its replication were repressed. These studies provide new insight into the
      complex interaction between two common human sexually transmitted viruses in an
      in vitro system, modeling their natural host tissue in vivo.

PMID- 14592759
TI  - Cucumovirus- and bromovirus-encoded movement functions potentiate cell-to-cell
      movement of tobamo- and potexviruses.
AB  - Cucumber mosaic virus (CMV, a cucumovirus) and Brome mosaic virus (BMV, a
      bromovirus) require the coat protein (CP) in addition to the 3a movement protein
      (MP) for cell-to-cell movement, while Cowpea chlorotic mottle virus (CCMV, a
      bromovirus) does not. Using bombardment-mediated transcomplementation assays, we
      investigated whether the movement functions encoded by these viruses potentiate
      cell-to-cell movement of movement-defective Tomato mosaic virus (ToMV, a
      tobamovirus) and Potato virus X (PVX, a potexvirus) mutants in Nicotiana
      benthamiana. Coexpression of CMV 3a and CP, but neither protein alone,
      complemented the defective movement of ToMV and PVX. A C-terminal deletion in CMV
      3a (3a Delta C33) abolished the requirement of CP in transporting the ToMV
      genome. The action of 3a Delta C33 was inhibited by coexpression of wild-type 3a.
      These findings were confirmed in tobacco with ToMV-CMV chimeric viruses. Either
      BMV 3a or CCMV 3a alone efficiently complemented the movement-defective phenotype
      of the ToMV mutant. Therefore, every 3a protein examined intrinsically possesses
      the activity required to act as MP. In transcomplementation of the PVX mutant,
      the activities of BMV 3a, CCMV 3a, and CMV 3a Delta C33 were very low. The
      activities of the bromovirus 3a proteins were enhanced by coexpression of the
      cognate CP but the activity of CMV 3a Delta C33 was not. Based on these results,
      possible roles of cucumo- and bromovirus CPs in cell-to-cell movement are
      discussed.

PMID- 14592760
TI  - AFV1, a novel virus infecting hyperthermophilic archaea of the genus acidianus.
AB  - We describe a novel virus, AFV1, of the hyperthermophilic archaeal genus
      Acidianus. Filamentous virions are covered with a lipid envelope and contain at
      least five different proteins with molecular masses in the range of 23-130 kDa
      and a 20.8-kb-long linear double-stranded DNA. The virus has been assigned to the
      family Lipothrixviridae on the basis of morphotypic characteristics. Host range
      is confined to several strains of Acidianus and the virus persists in its hosts
      in a stable carrier state. The latent period of virus infection is about 4 h.
      Viral DNA was sequenced and sequence similarities were found to the
      lipothrixvirus SIFV, the rudiviruses SIRV1 and SIRV2, as well as to conjugative
      plasmids and chromosomes of the genus Sulfolobus. Exceptionally for the linear
      genomes of archaeal viruses, many short direct repeats, with the sequence TTGTT
      or close variants thereof, are closely clustered over 300 bp at each end of the
      genome. They are reminiscent of the telomeric ends of linear eukaryal
      chromosomes.

PMID- 14592761
TI  - An anti-HIV-1 gp120 antibody expressed as an endocytotic transmembrane protein
      mediates internalization of HIV-1.
AB  - In this study, we used HIV-1 as a model to demonstrate a novel approach for
      receptor-independent cell entry of virus. The heavy chain of an anti-HIV-1 gp120
      antibody was engineered with endocytotic and transmembrane motifs from either the
      cation-independent mannose 6-phosphate receptor or the low-density lipoprotein
      receptor. Flow cytometry and immunofluorescence studies showed that the chimeric
      antibodies were expressed on the cell surface and can undergo rapid
      internalization. Furthermore, one of the chimeric antibodies was able to bind and
      internalize HIV-1. Using a luciferase reporter HIV-1, we further showed that
      internalized viruses could undergo replication. Therefore, we have demonstrated a
      proof-of-principle of a novel method that can be used to internalize virus into
      cells, without prior knowledge of the cellular receptor for the virus. We propose
      that this approach would be particularly useful for studying viruses whose
      cellular receptor(s) is not known.

PMID- 14592762
TI  - Changing immunodominance patterns in antiviral CD8 T-cell responses after loss of
      epitope presentation or chronic antigenic stimulation.
AB  - The H-2(b)-restricted CD8 T-cell response against lymphocytic choriomeningitis
      virus is directed against at least 10 dominant and subdominant epitopes,
      including two newly identified epitopes in the nucleoprotein. We have used this
      set of epitopes to characterize the plasticity of the hierarchy under different
      experimental circumstances, i.e., loss of MHC class I molecules, loss of specific
      epitopes (CTL escape), and prolonged antigenic stimulation (chronic infection).
      We found that loss of epitope-specific responses was almost inevitably associated
      with compensatory responses against other, subdominant, epitopes. Multiple
      epitope loss was required to change the hierarchy. Persistent viral infection was
      associated with a loss of not only the dominant response against the NP396
      epitope, but also a loss of subdominant responses against nucleoprotein epitopes.
      In contrast, responses against glycoprotein epitopes, dominant and subdominant,
      survived under chronic infection conditions, and even dominated the response
      (GP118). Our results suggest that the fate of each specific T-cell response
      during chronic infection is in part determined by the origin of the cognate
      epitopes, i.e, the proteins from which they are processed, or, more specifically,
      nucleoprotein versus glycoprotein. A model in which recruitment time plays a role
      in the longevity of antiviral T-cell responses during persistent infection is
      discussed.

PMID- 14592763
TI  - A novel technique with enhanced detection and quantitation of HPV-16 E1- and E2
      mediated DNA replication.
AB  - Transient DNA replication assays to detect papillomavirus E1/E2-mediated DNA
      replication have depended upon Southern blotting. This technique is hazardous
      (radioactive), labour intensive, semiquantitative, and physically limited in the
      number of samples that can be processed at any one time. We have overcome these
      problems by developing a real-time PCR protocol for the detection of E1/E2
      mediated transient DNA replication. The results demonstrate detection of
      replication at levels not seen using Southern blotting demonstrating enhanced
      sensitivity. This technique is also, by definition, highly quantitative.
      Therefore, the real-time PCR technique is the optimal method for the detection of
      E1/E2-mediated DNA replication.

PMID- 14592764
TI  - Apoptosis of infiltrating T cells in the central nervous system of mice infected
      with Theiler's murine encephalomyelitis virus.
AB  - Theiler murine encephalomyelitis virus (TMEV), DA strain, induces in susceptible
      strain of mice a biphasic disease consisting of early acute disease followed by
      late chronic demyelinating disease. Both phases of the disease are associated
      with inflammatory infiltrates of the central nervous system (CNS). Late chronic
      demyelinating disease induced by TMEV serves as an excellent model to study human
      demyelinating disease, multiple sclerosis. During early acute disease, the virus
      is partially cleared from the CNS by CD3(+) T cells. These T cells express Fas,
      FasL, negligible levels of Bcl-2 proteins and undergo activation-induced cell
      death as determined by TUNEL assay leading to resolution of the inflammatory
      response. In contrast, during late chronic demyelinating disease, and despite
      dense perivascular and leptomeningeal infiltrates, only very few cells undergo
      apoptosis. Mononuclear cells infiltrating the CNS express Bcl-2. It appears that
      the lack of apoptosis of T cells during late chronic demyelinating disease leads
      to the accumulation of these cells in the CNS. These cells may play a role in the
      pathogenesis of the demyelinating disease.

PMID- 14592765
TI  - Epitope mapping and characterization of a novel CD4-induced human monoclonal
      antibody capable of neutralizing primary HIV-1 strains.
AB  - Human immunodeficiency virus (HIV-1) enters target cells by binding its gp120
      exterior envelope glycoprotein to CD4 and one of the chemokine receptors, CCR5 or
      CXCR4. CD4-induced (CD4i) antibodies bind gp120 more efficiently after CD4
      binding and block the interaction with the chemokine receptor. Examples of CD4i
      antibodies are limited, and the prototypes of the CD4i antibodies exhibit only
      weak neutralizing activity against primary, clinical HIV-1 isolates. Here we
      report the identification of a novel antibody, E51, that exhibits CD4-induced
      binding to gp120 and neutralizes primary HIV-1 more efficiently than the
      prototypic CD4i antibodies. The E51 antibody blocks the interaction of gp120-CD4
      complexes with CCR5 and binds to a highly conserved, basic gp120 element composed
      of the beta 19-strand and surrounding structures. Thus, on primary HIV-1
      isolates, this gp120 region, which has been previously implicated in chemokine
      receptor binding, is accessible to a subset of CD4i antibodies.

PMID- 14592766
TI  - Translocation of the B cell receptor to lipid rafts is inhibited in B cells from
      BLV-infected, persistent lymphocytosis cattle.
AB  - Bovine leukemia virus (BLV) infection causes a significant polyclonal expansion
      of CD5(+), IgM+ B lymphocytes known as persistent lymphocytosis (PL) in
      approximately 30% of infected cattle. There is evidence that this expanded B cell
      population has altered signaling, and resistance to apoptosis has been proposed
      as one mechanism of B cell expansion. In human and murine B cells, antigen
      binding initiates movement of the B cell receptor (BCR) into membrane
      microdomains enriched in sphingolipids and cholesterol, termed lipid rafts. Lipid
      rafts include members of the Src-family kinases and exclude certain phosphatases.
      Inclusion of the BCR into lipid rafts plays an important role in regulation of
      early signaling events and subsequent antigen internalization. Viral proteins may
      also influence signaling events in lipid rafts. Here we demonstrate that the
      largely CD5(+) B cell population in PL cattle has different mobilization and
      internalization of the BCR when compared to the largely CD5-negative B cells in
      BLV-negative cattle. Unlike B cells from BLV-negative cattle, the BCR in B cells
      of BLV-infected, PL cattle resists movement into lipid rafts upon stimulation and
      is only weakly internalized. Expression of viral proteins as determined by
      detection of the BLV transmembrane (TM) envelope glycoprotein gp30 did not alter
      these events in cells from PL cattle. This exclusion of the BCR from lipid rafts
      may, in part, explain signaling differences seen between B cells of BLV-infected,
      PL, and BLV-negative cattle and the resistance to apoptosis speculated to
      contribute to persistent lymphocytosis.

PMID- 14592767
TI  - SV40 17KT antigen complements dnaj mutations in large T antigen to restore
      transformation of primary human fibroblasts.
AB  - Transformation of human cells requires both SV40 large T and small t antigens.
      Plasmids that contained mutations in the amino-terminal dnaJ domain of the early
      region fail to transform human diploid fibroblasts. However, large T dnaJ mutants
      can be rescued by plasmids that express early region products other than large T
      antigen. The protein found to be responsible for such complementation was the
      third early region product, 17KT. Similar to large T, this protein reduces levels
      of the retinoblastoma-related protein, p130, and stimulates cell-cycle
      progression of quiescent fibroblasts, two activities of large T that are
      disrupted by dnaJ mutations.

PMID- 14592768
TI  - Recurring conformation of the human immunodeficiency virus type 1 gp120 V3 loop.
AB  - The crystal structure of the human immunodeficiency virus type 1 (HIV-1)
      neutralizing, murine Fab 83.1 in complex with an HIV-1 gp120 V3 peptide has been
      determined to 2.57 A resolution. The conformation of the V3 loop peptide in
      complex with Fab 83.1 is very similar to V3 conformations seen previously with
      two other neutralizing Fabs, 50.1 and 59.1. The repeated identification of this
      same V3 conformation in complex with three very different, neutralizing
      antibodies indicates that it is a highly preferred structure for V3 loops on some
      strains of the HIV-1 virus.

PMID- 14592769
TI  - Common RNA replication signals exist among group 2 coronaviruses: evidence for in
      vivo recombination between animal and human coronavirus molecules.
AB  - 5' and 3' UTR sequences on the coronavirus genome are known to carry cis-acting
      elements for DI RNA replication and presumably also virus genome replication. 5'
      UTR-adjacent coding sequences are also thought to harbor cis-acting elements.
      Here we have determined the 5' UTR and adjacent 289-nt sequences, and 3' UTR
      sequences, for six group 2 coronaviruses and have compared them to each other and
      to three previously reported group 2 members. Extensive regions of highly similar
      UTR sequences were found but small regions of divergence were also found
      indicating group 2 coronaviruses could be subdivided into those that are bovine
      coronavirus (BCoV)-like (BCoV, human respiratory coronavirus-OC43, human enteric
      coronavirus, porcine hemagglutinating encephalomyelitis virus, and equine
      coronavirus) and those that are murine hepatitis virus (MHV)-like (A59, 2, and
      JHM strains of MHV, puffinosis virus, and rat sialodacryoadenitis virus). The 3'
      UTRs of BCoV and MHV have been previously shown to be interchangeable. Here, a
      reporter-containing BCoV DI RNA was shown to be replicated by all five BCoV-like
      helper viruses and by MHV-H2 (a human cell-adapted MHV strain), a representative
      of the MHV-like subgroup, demonstrating group 2 common 5' and 3' replication
      signaling elements. BCoV DI RNA, furthermore, acquired the leader of HCoV-OC43 by
      leader switching, demonstrating for the first time in vivo recombination between
      animal and human coronavirus molecules. These results indicate that common
      replication signaling elements exist among group 2 coronaviruses despite a two
      cluster pattern within the group and imply there could exist a high potential for
      recombination among group members.

PMID- 14592770
TI  - Biology of the temperate Streptococcus thermophilus bacteriophage TP-J34 and
      physical characterization of the phage genome.
AB  - The temperate Streptococcus thermophilus bacteriophage TP-J34 was identified in
      the lysogenic host strain J34. The majority of phage particles produced upon
      induction was defective and noninfectious, consisting of DNA-filled heads lacking
      tails. A physical map (45.6 kb) was established. Analysis of minor restriction
      bands of the DNA isolated from phage particles as well as the analysis of the
      protein pattern indicated that phage TP-J34 is a pac-type phage. This was
      confirmed by immunoelectron microscopy using antisera raised against virulent cos
      and pac-type S. thermophilus phages. The lysogenic host J34 but not its
      noninducible derivate J34-12 contained phage DNA in the nonintegrated state and
      exhibited autolysis at elevated temperatures. Prophage-carrying strains grew
      homogeneously while 16 of 20 prophage-cured derivatives aggregated and sedimented
      rapidly. When phage TP-J34 was propagated lytically on a prophage-cured host
      strain, a 2.7-kb site-specific deletion occurred in the phage genome. This
      deletion was also identified in the prophage DNAs of relysogenized strains.

PMID- 14592771
TI  - Molecular analysis of a recombinant M-MuLV/RaLV retrovirus.
AB  - A replication-competent retrovirus was isolated from Rat1 cells after stable
      transfection of a defective Moloney murine leukemia virus (M-MuLV) provirus
      bearing mutations in two conserved cysteines of the TM protein.
      Immunoprecipitation of the viral proteins indicated the infectious virus is not
      related to M-MuLV. Electron microscopy of budding virions revealed a mammalian
      type C virus. The host range of the virus is limited to rat cells. N-terminal
      sequence analysis of the capsid-associated protein identified the virus to be
      related to rat leukemia virus (RaLV). Analysis of the cloned sequences indicated
      a recombinant provirus with a genetic organization in which the leader region and
      open reading frames of the endogenous RaLV are flanked by identical M-MuLV LTRs
      at both ends. These results highlight the effects of exogenous viral infection on
      endogenous viruses.

PMID- 14592772
TI  - Replacement of the murine leukemia virus (MLV) envelope gene with a truncated HIV
      envelope gene in MLV generates a virus with impaired replication capacity.
AB  - Murine leukemia virus (MLV) capsid particles can be efficiently pseudotyped with
      a variant of the HIV-1 envelope protein (Env) containing the surface glycoprotein
      gp120-SU and a carboxyl-terminally truncated transmembrane (TM) protein, with
      only seven cytoplasmic amino acids. MLV/HIV pseudotyped vector particles acquire
      the natural host tropism of HIV-1 and their entry is dependent on the presence of
      CD4 and an appropriate co-receptor on the surface of the target cell. We describe
      here the construction of chimeric MLV/HIV proviruses containing the truncated HIV
      envelope gene. The MLV/HIV provirus was generated by direct replacement of the
      MLV envelope gene with HIV Env coding sequences either with or without the
      additional inclusion of the woodchuck hepatitis virus posttranscriptional
      regulatory element (WPRE). Chimeric MLV/HIV particles could be generated from
      transfected 293T cells and were able to infect CD4/CXCR4-positive target cells.
      However, the second round of infection of target cells was severely impaired,
      despite the fact that the WPRE element enhanced the amount of viral mRNA
      detected. Viral particles released from infected cells showed reduced HIV Env
      incorporation, indicating that additional factors required for efficient
      replication of MLV/HIV pseudotyped viruses are missing.

PMID- 14592773
TI  - Caprine arthritis-encephalitis virus-infected goats can generate human
      immunodeficiency virus-gp120 cross-reactive antibodies(1).
AB  - Lentiviruses display surprisingly disparate clinical manifestations in their
      specific hosts, share complex genetic structures, and exhibit extensive
      diversity, particularly in their envelope genes. The envelope protein, gp135, of
      caprine arthritis-encephalitis virus (CAEV) has minimal primary sequence homology
      to gp120, the envelope protein of human immunodeficiency virus (HIV).
      Nevertheless, they bear certain similarities in that they both possess five
      variable regions, both are heavily glycosylated, and both share short sequence
      motifs. We establish a further relationship and demonstrate that some goats,
      infected with CAEV, possess gp135-specific antibodies which cross-react with
      gp120 from several HIV strains, provided the protein is expressed in insect
      cells. We show that, although the cross-reactivity of these immunoglobulins
      depends on the level of glycosylation, nevertheless, some antibodies recognize
      the protein epitopes on gp120, at least some of which are linear in character.
      Further characterization of this unexpected cross-reaction will define its
      potential therapeutic utility.

PMID- 14592774
TI  - Evaluating the role of CRM1-mediated export for adenovirus gene expression.
AB  - A complex of the Adenovirus (Ad) early region 1b 55-kDa (E1b-55kDa) and early
      region 4 ORF6 34-kDa (E4-34kDa) proteins promotes viral late gene expression. E1b
      55kDa and E4-34kDa have leucine-rich nuclear export signals (NESs) similar to
      that of HIV Rev. It was proposed that E1b-55kDa and/or E4-34kDa might promote the
      export of Ad late mRNA via their Rev-like NESs, and the transport receptor CRM1.
      We treated infected cells with the cytotoxin leptomycin B to inhibit CRM1
      mediated export; treatment initially delays the onset of late gene expression,
      but this activity completely recovers as the late phase progresses. We find that
      the E1b-55kDa NES is not required to promote late gene expression. Previous
      results showed that E4-34kDa-mediated late gene expression does not require an
      intact NES (J. Virol. 74 (2000), 6684-6688). Our results indicate that these Ad
      regulatory proteins promote late gene expression without intact NESs or active
      CRM1.

PMID- 14592775
TI  - Adenovirus E4-34kDa requires active proteasomes to promote late gene expression.
AB  - A complex of the Adenovirus (Ad) early region 1b 55-kDa protein (E1b-55kDa) and
      the early region 4 ORF6 34-kDa protein (E4-34kDa) promotes viral late RNA
      accumulation in the cytoplasm while inhibiting the transport of most newly
      synthesized cellular mRNA. The E4 ORF3 11-kDa protein (E4-11kDa) functionally
      compensates for at least some of the activities of this complex. We find that the
      same large central region of E4-34kDa that is required for proteasome-mediated
      degradation of p53 (J. Virol. 75, (2001) 699-709) is also required to promote
      viral late gene expression in a complementation assay. E4-34kDa does not promote
      late gene expression in complementation assays performed in the presence of
      proteasome inhibitors. A proteasome inhibitor also dramatically reduced late gene
      expression by a virus that lacks the E4-11kDa gene and therefore relies on E4
      34kDa for late gene expression. Our results suggest that E4-34kDa activity in
      promoting late gene expression depends on the proteasome.

PMID- 14592776
TI  - T cell survival/proliferation reconstitution by trifluoperazine in human
      immunodeficiency virus-1 infection.
AB  - Recent findings support an indirect relationship between T cell depletion in HIV
      1 infection and the rate of virus replication with implications for treatment
      strategies. We have initiated a new approach to recover immune function through
      the use of novel chemical agents. A cationic amphiphilic drug that binds to
      Ca(2+)-calmodulin at high concentrations, [10-[3-(4-methyl-1-piperazinyl)-propyl]
      2- (trifluoromethyl)-(10)H-phenothiazine dihydrochloride] [denoted
      trifluroperazine dihydrochloride (Tfp); molecular weight 480.43] TFP was found at
      low concentrations (10(-6) to 10(-10) M) to help T cells from AIDS patients to
      restore proliferation in vitro. Here we show that the Tfp molecule can restore
      the cell survival of T lymphocytes from PBMCs derived from HIV-1-infected
      patients in vitro. Tfp enhances T cell proliferation and Th-cell responses by
      selectively inhibiting cell mortality and apoptosis. The restored antigen
      specific response is associated with the synthesis of IL-2 and gamma-interferon.
      Even though this drug does not possess any detectable antiviral effect, it might
      be considered as a potential therapeutic agent in HIV-infected patients, to
      correct immune defects. Besides antiviral compounds, these data may facilitate
      immune reconstitution in patients with HIV infection and other immunosuppressive
      diseases.

PMID- 14592777
TI  - Enterovirus 71 contains a type I IRES element that functions when eukaryotic
      initiation factor eIF4G is cleaved.
AB  - Human enterovirus 71 (EV71) is a member of the Enterovirus genus of the
      Picornaviridae family. Other members of this family utilize an unusual mechanism
      of translation initiation whereby ribosomes are recruited internally to the viral
      RNA by an internal ribosome site (IRES) located in their 5' noncoding regions (5'
      NCR). Using dicistronic reporter constructs, we demonstrate that the 5' NCRs of
      the 7423/MS/87 and BrCr strains of EV71 function as an IRES both in extracts and
      in cultured cells. Preincubation of translation extracts with purified
      coxsackievirus 2A protease cleaved elF4G, a component of the cap binding complex,
      resulting in a significant decrease in translation of capped mRNAs. In contrast,
      the translational efficiency of the EV71 IRES was enhanced under this condition,
      demonstrating that the EV71 IRES functions similar to other enterovirus IRES
      elements when components of the cap binding protein complex are cleaved. Finally,
      insertion of an upstream, out-of-frame start codon in the 5' NCR of the EV71
      genome inhibited IRES activity, suggesting that EV71 can be classified as a type
      I IRES, in which ribosomes first bind upstream of the initiation codon and then
      scan the mRNA until an appropriate downstream AUG start codon is encountered and
      protein synthesis commences.

PMID- 14592778
TI  - Gastric mucosal fibrosis: a novel explanation for dyspepsia.
AB  - The etiology of functional dyspepsia has not been discerned yet which has led to
      inadequate treatment of this disease. It remains a common disorder with expensive
      and yet often ineffective therapy. We propose that the pathogenesis of this
      disease lies in the histological and ultrastructural changes inflicted on the
      gastric mucosa in chronic gastritis and fibrosis. This hypothesis, if
      substantiated will provide for therapy which will be based on the pathogenesis of
      the disease and which will be cheaper and easily available to most. It will also
      add impetus to the early eradication of Helicobacter pylori, which would prevent
      chronic gastritis and hence gastric fibrosis.

PMID- 14592779
TI  - Is somnambulism a distinct disorder of humans and not seen in non-human primates?
AB  - Though somnambulism (sleepwalking) is a well-recognized sleep disorder in humans,
      a biomedical literature search in Medline and Primate Literature bibliographic
      databases showed no publications on sleepwalking in non-human primates. From this
      finding, two inferences can be made. First is that somnambulism may be present in
      non-human primates; but due to limitations in expertise and methodological
      resources as well as narrow focus of research interest, until now researchers
      have not detected it in wild and/or captive conditions. Second, somnambulism does
      not exist in non-human primates including apes (chimpanzee, gorilla, orang-utan
      and gibbon); and thus, it is a unique behavioral disorder present only in humans.
      It is premature to conclude which of these two inferences is correct. In Jane
      Goodall's view, sleepwalking behavior is absent in chimpanzees. If further field
      observations can confirm Goodall's assertion that somnambulism is indeed absent
      in chimpanzees, it will be of evolutionary and medical interest to know why this
      parasomnic behavior became established in humans during the past 5.5 million
      years or so.

PMID- 14592780
TI  - Cytokine-serotonin interaction through IDO: a neurodegeneration hypothesis of
      depression.
AB  - There are different theories and hypotheses related to the aetiology of
      depression. The interaction between brain 5-HT level and the activity of its
      autoreceptors plays a role in mood changes and depression. In major depression,
      activation of the inflammatory response system (IRS) and, increased
      concentrations of proinflammatory cytokines, prostaglandin E2 and negative immuno
      regulatory cytokines in peripheral blood have been reported. Recently, pro
      inflammatory cytokines have been found to have profound effects on the metabolism
      of brain serotonin through the enzyme indoleamine-2,3-dioxygenase (IDO) that
      metabolizes the tryptophan, the precursor of 5-HT to neurodegenerative
      quinolinate and neuroprotective kynurenate. The cytokine-serotonin interaction
      that leads to the challenge between quinolinate and kynurenate in the brain
      explains the neurodegeneration hypothesis of depression.

PMID- 14592781
TI  - Idiopathic intracranial hypertension and idiopathic normal pressure
      hydrocephalus: diseases with opposite pathogenesis?
AB  - Idiopathic intracranial hypertension (IDICH) and idiopathic normal pressure
      hydrocephalus (IDNPH) are disorders of the circulation of the cerebrospinal fluid
      (CSF) with opposite diagnostic features, obscure etiology but the same treatment:
      CSF drainage. In both diseases a large quantity of CSF exists: equilibrated by
      the brain edema in IdICH with high ICP and not equilibrated by brain pressure,
      and the ventricles are enlarged in IdNPH. The same anatomical structure involved
      in both diseases is the ventricular wall and this represents a true barrier, a
      glial-ependymal barrier and it acts as a barrier only in connection with the
      difference between the pressures. The spontaneous course of both diseases
      suggests that an open glial-ependymal barrier protects the brain parenchyma.

PMID- 14592782
TI  - Simultaneous hypersecretion of CSF and of brain interstitial fluid causes
      idiopathic intracranial hypertension.
AB  - Idiopathic intracranial hypertension (IdICH) is a high intracranial pressure and
      no evidence of intracranial lesions or hydrocephalus. The characteristics of
      IdICH and the anatomical and physiological data show that the mechanisms of
      elaboration of the interstitial fluid at blood-brain barrier (BBB) and of
      cerebrospinal fluid (CSF) at choroid plexus are very similarly. In IdICH many
      pathological conditions can induce the simultaneous hypersecretion of CSF and of
      the brain interstitial fluid and the high intracranial pressure (ICP) of CSF is
      equalized simultaneously of the pressure of the brain interstitial fluid. The
      cerebral blood flow is maintained quasinormal in IdICH, even increased, so that
      it occurs a fast absorption of CSF and of interstitial fluid and the brain injury
      is insignificantly despite the high ICP. Therefore idiopathic intracranial
      hypertension occurs through simultaneous hypersecretion of the cerebrospinal
      fluid and of the cerbral interstitial fluid followed by a rapid circulation and
      absorption of these fluids based on a fast cerebral blood flow.

PMID- 14592783
TI  - Varicella inoculation to prevent shingles, and cytomegalovirus inoculation to
      prevent cytomegalovirus associated graft failures.
AB  - I suggest varicella virus inoculation be considered to reduce the risk of herpes
      zoster (the shingles), and cytomegalovirus (CMV) inoculation be considered to
      reduce the risk of CMV associated transplant graft failure. Such inoculations are
      inexpensive and easy to implement, and are simple potential solutions to common
      and often severe medical problems with suboptimal current treatments.

PMID- 14592784
TI  - PTH excess may promote weight gain by impeding catecholamine-induced lipolysis
      implications for the impact of calcium, vitamin D, and alcohol on body weight.
AB  - Increased free intracellular calcium ([Ca(2+)](i)) in adipocytes blunts the
      lipolytic response to catecholamines by activating phosphodiesterase 3B - the
      same enzyme that mediates the antilipolytic effect of insulin - while also
      compromising the efficiency of insulin-stimulated glucose uptake. Physiological
      increases in parathyroid hormone (PTH) have been shown to increase [Ca(2+)](i) in
      adipocytes. These considerations may rationalize recent evidence that high
      dietary intakes of calcium and/or dairy products may reduce risk for obesity,
      diabetes, and insulin-resistance syndrome, and they predict that other dietary
      measures which down-regulate PTH - such as good vitamin D status, and moderation
      in phosphate and salt intakes - may likewise be beneficial in these respects.
      Consistent with this position are reports that body weight is elevated in elderly
      subjects with both primary and secondary hyperparathyroidism; furthermore,
      insulin resistance is a well-known complication of both forms of
      hyperparathyroidism. The fact that regular alcohol consumption is associated with
      decreased PTH secretion may help to explain why moderate drinkers are less prone
      to insulin resistance, diabetes, and - in women - obesity. Down-regulation of PTH
      cannot be expected to promote dramatic weight loss, but in the long-term it may
      lessen risk for significant weight gain and diabetes, and conceivably may
      potentiate the fat loss achievable with caloric restriction and/or exercise.

PMID- 14592785
TI  - A moderately low phosphate intake may provide health benefits analogous to those
      conferred by UV light - a further advantage of vegan diets.
AB  - Although exposure to ultraviolet light is often viewed as pathogenic owing to its
      role in the genesis of skin cancer and skin aging, there is growing
      epidemiological evidence that such exposure may decrease risk for a number of
      more serious cancers, may have a favorable impact on blood pressure and vascular
      health, and may help to prevent certain autoimmune disorders - in addition to its
      well-known influence on bone density. Most likely, these health benefits are
      reflective of improved vitamin D status. Increased synthesis or intake of vitamin
      D can be expected to down-regulate parathyroid hormone (PTH), and to increase
      autocrine synthesis of its active metabolite calcitriol in certain tissues; these
      effects, in turn, may impact cancer risk, vascular health, immune regulation, and
      bone density through a variety of mechanisms. Presumably, a truly adequate
      supplemental intake of vitamin D - manyfold higher than the grossly inadequate
      current RDA - could replicate the benefits of optimal UV exposure, without
      however damaging the skin. Diets moderately low in bioavailable phosphate - like
      many vegan diets - might be expected to have a complementary impact on disease
      risks, inasmuch as serum phosphate suppresses renal calcitriol synthesis while up
      regulating that of PTH. A proviso is that the impact of dietary phosphorus on
      bone health is more equivocal than that of vitamin D. Increased intakes of
      calcium, on the other hand, down-regulate the production of both PTH and
      calcitriol - the latter effect may explain why the impact of dietary calcium on
      cancer risk (excepting colon cancer), hypertension, and autoimmunity is not
      clearly positive. An overview suggests that a vegan diet supplemented with high
      dose vitamin D should increase both systemic and autocrine calcitriol production
      while suppressing PTH secretion, and thus should represent a highly effective way
      to achieve the wide-ranging health protection conferred by optimal UV exposure.

PMID- 14592786
TI  - Iatrogenic lipodystrophy in HIV patients - the need for very-low-fat diets.
AB  - In HIV patients, chronic treatment with protease inhibitors often precipitates a
      peripheral lipodystrophy associated with insulin resistance syndrome and
      premature coronary disease. In vitro studies demonstrate that these drugs can
      compromise the ability of adipocytes to store triglycerides; in vivo, peripheral
      subcutaneous adipocytes appear to be most affected, such that body fat often
      redistributes to visceral or truncal adipose stores. Dysfunction of peripheral
      subcutaneous adipocytes - ordinarily quite efficient for storing fat - can be
      expected to give rise to an excessive flux of free fatty acids (FFAs) following
      fatty meals; chronic overexposure of tissues to FFAs is a likely explanation for
      the insulin resistance syndrome associated with lipodystrophy. These
      considerations suggest that a very-low-fat diet - less than 15% fat calories -
      may ameliorate the cardiovascular risk associated with lipodystrophy; such diets
      are known to have a favorable effect on the insulin sensitivity of healthy
      subjects. Very-low-fat whole-food vegan diets are particularly recommendable in
      this context, as they may help to shrink visceral fat depots while markedly
      reducing LDL cholesterol. Appropriate adjunctive measures may include aerobic
      exercise training - beneficial both for insulin sensitivity and weight control -
      as well as administration of statins or policosanol, and of fibrates or fish oil,
      to decrease LDL and triglycerides, respectively. Despite perceptions to the
      contrary, very-low-fat diets can meet with good compliance in well-motivated
      subjects given appropriate instruction.

PMID- 14592787
TI  - Hyperinsulinemia may boost both hematocrit and iron absorption by up-regulating
      activity of hypoxia-inducible factor-1alpha.
AB  - There is growing evidence that increases in both hematocrit and body iron stores
      are components of the insulin resistance syndrome. The ability of insulin and of
      IGF-I - whose effective activity is increased in the context of insulin
      resistance - to boost activity of the transcription factor hypoxia-inducible
      factor-1alpha (HIF-1alpha), may be at least partially responsible for this
      association. HIF-1alpha, which functions physiologically as a detector of both
      hypoxia and iron-deficiency, promotes synthesis of erythropoietin, and may also
      mediate the up-regulatory impact of hypoxia on intestinal iron absorption.
      Insulin/IGF-I may also influence erythropoiesis more directly, as they are growth
      factors for developing reticulocytes. Conversely, the activation of HIF-1alpha
      associated with iron deficiency may be responsible for the increased glucose
      tolerance noted in iron-deficient animals; HIF-1alpha promotes efficient glucose
      uptake and glycolysis - a sensible adaptation to hypoxia - by inducing increased
      synthesis of glucose transporters and glycolytic enzymes. Recent reports that
      phlebotomy can increase the efficiency of muscle glucose uptake in lean healthy
      omnivores are intriguing and require further confirmation. Whether increased iron
      stores contribute to the elevated vascular risk associated with insulin
      resistance is doubtful, inasmuch as most prospective studies fail to correlate
      serum ferritin or transferrin saturation with subsequent vascular events.
      However, current data are reasonably consistent with the possibility that
      moderately elevated iron stores are associated with increased overall risk for
      cancer - and for colorectal cancer in particular; free iron may play a catalytic
      role in 'spontaneous' mutagenesis. Thus, iron excess may mediate at least some of
      the increased cancer risk associated with insulin resistance and heme-rich diets.
      People who are insulin resistant can minimize any health risk associated with
      iron overload by avoiding heme-rich flesh foods and donating blood regularly.

PMID- 14592788
TI  - Regulation of E-kinase mediated cell-adhesion molecule(s) function by E
      NTPase(s): imminent regulatory inter-dependency for cell adhesion.
AB  - E-NTPase is a cell membrane bound enzyme, suggested to play a role in maintaining
      the [NTP](o) and cell adhesion. Attempts to purify this enzyme resulted
      identification of many proteins co-purifying with E-NTPase. The amino acid
      sequence of chicken gizzard smooth muscle E-NTPase has been shown to have
      considerable amino acid sequence homology with mammalian CD39. On the other hand,
      the purified rat cardiac sarcolemmal E-NTPase showed identical sequence homology
      with platelet CD36. In this communication, an effort was made to provide
      rationale for the functional relevance of E-NTPase with reference to cell
      adhesion process.

PMID- 14592789
TI  - Neutrophil chemotaxis: potential role of chemokine receptors in extracellular
      nucleotide induced Mac-1 expression.
AB  - Extracellular nucleotide-induced stimulation and activation of neutrophil in the
      inflammatory foci followed by chemotaxis in to inflamed vasculature plays a
      critical role in inflammatory diseases and coronary artery diseases. The
      extracellular nucleotides stimulate a P2Y receptor(s) on human PMN with the
      pharmacological profile similar to that of the P2Y2 receptor. Consequent to the
      activation of P2Y2, arachidonic acid is formed from the membrane bound lipids by
      phospholipase A2, which subsequently metabolized by 5 lipoxygenase to form the
      leukotrienes. Of the several leukotrienes generated, LTB(4) is a potent
      proinflammatory chemokine. Upon its release LTB(4) binds to the PMN by autocrine
      manner in the same neutrophil and also in a paracrine manner to other
      neutrophils, leading to the accelerated Mac-1 expression on PMN membrane
      resulting chemotaxis. Thus it is suggested that the extracellular nucleotide(s)
      released from the activated platelets and other damaged cell types exacerbate
      inflammatory response by leukotriene generation. In turn the leukotriene will act
      in both autocrine and paracrine manner to amplify the process of chemotaxis in
      PMN by upregulation of Mac-1 expression.

PMID- 14592790
TI  - Hyperhomocysteinemia may be a resistance factor in tocolytic treatment with beta
      mimetics.
AB  - Homocysteine is an intermediate amino acid in the methionine metabolism which
      does not take place in the structure of proteins. Plasma homocysteine levels can
      be elevated by a variety of genetic and nutritional factors. Hyperhomocysteinemia
      is an independent risk factor for cardiovascular diseases and common obstetric
      problems. Mildly elevated levels of homocysteine have been implicated in a number
      of disease processes such as atherosclerotic vascular disease and adverse
      obstetrical outcome. It was shown that the presence of high homocysteine
      concentrations in the in vitro system had an activating role in myometrial
      contractions. It is hypothesized that hyperhomocysteinemia in pregnancy is
      associated with preterm labor in consequence of myometrial contractions.
      Hyperhomocysteinemia, therefore, could be a treatable cause of this important
      public health and obstetric concern.

PMID- 14592792
TI  - Deterministic hypotheses on the origin of life and of its reproduction.
AB  - The current theory of the origin of life by random polymerisation and selection
      of nucleic acids is challenged by the hypothesis that the primitive enzymatic
      sites would have been formed by abiotic polymerisation of aminoacids,
      specifically gathered (by saline, hydrogen, or hydrophobic interactions), around
      the different substrates. The information contained in these proteinoids would
      have been transferred to messenger-like RNAs by a mechanism reverse of that of
      the present protein synthesis, and then to DNA. The interactions between
      aminoacids and nucleotidic sequences would have been at the origin of the genetic
      code, as hypothesized by several authors. We propose that the specificity of the
      bindings would have been enhanced and 'frozen' by ternary associations with
      specific proteinoids (future aminoacyl tRNA synthetases). The role of chance
      would have been limited to the supply of the products and to the determination of
      the conditions of reaction. Thermodynamic considerations (dissipation of the free
      enthalpy through enzymatic activities) may explain the emergence of the
      biological systems.

PMID- 14592791
TI  - An interaction between type 1 and type 2 programmed cell death and clonogenic
      survival.
AB  - We suggest two additional reasons why current, non-surgical therapies for most
      solid, epithelial-derived cancers can lack effectiveness. Studies with panc-1
      human pancreatic cancer cells cultured with actinomycin D and/or MK 886 indicate
      firstly, that type 2 (intrinsic, autophagic, mitochondrial-dependent, MK 886
      induced) programmed cell death is less effective than the type 1 (apoptotic,
      extrinsic, ligand-dependent, actinomycin D-induced) form in reducing the number
      of residual clonogenic cells, and secondly, that activation of cellular suicide
      during their combined culture results in a greater number of residual clonogenic
      cells compared with either agent alone. HYPOTHESIS: Based on results from the
      culture of panc-1 cells with MK 886 and/or actinomycin D, we suggest that in this
      system, and possibly in others: (a) type 2 programmed cell death is a less
      effective inhibitor of residual cells with clonogenic potential, and (b)
      activation together of both forms of PCD increases the number of residual
      clonogenic cells.

PMID- 14592793
TI  - The function of 'brain waves': a cybernetic model of electroencephalography.
AB  - Electroencephalograms recorded from sleeping subjects are reinterpreted, from
      first principles, to explain the relationship between the observed wave-forms and
      cerebral processes. The manifestations of narcolepsy, namely, sleep paralysis,
      hypnopompic hallucinations and cataplexy are consistent with a hypothesis that
      the disorder is the result of entrainment of cerebral waves, causing almost
      instantaneous descent into a REM sleep state.

PMID- 14592794
TI  - Topological aspects of axonal regeneration.
AB  - The fibers making up any sensory system in the spinal cord come from the same
      cells as do the fibers in peripheral nerves yet severed nerve fibers in the adult
      spinal cord do not regenerate but damaged peripheral nerves - those in the
      extremities - do heal themselves. Why should spinal cord regeneration even be an
      issue, why should an inhibiting protein have evolved to prevent it and what
      causes this protein to be expressed? From a holistic perspective, an answer to
      this conundrum shows that these questions are intertwined, and suggests that: (1)
      The model of the neurons as 'wires' is too simplistic. (2) In humans, the 'map'
      of individual connections is (topologically, at least) locally variable, though
      the overall global topology and 'functionality' of each normal spinal cord is
      constant. Both of these issues have to be addressed if functional restoration is
      to be achieved.

PMID- 14592795
TI  - Sudden infant death syndrome: a cybernetic etiology.
AB  - The brain's processes, by hypothesis, involve information processing by an
      extraordinarily complex, highly sophisticated, self-organizing cybernetic system
      embedded in the central nervous system. This cybernetic system generates itself
      in successive stages. Breathing is, by default, an autonomous function, but
      breath control is learned. If there is not a smooth transfer of function at the
      time when a successor system (one that enables autonomous breathing to be
      overridden by voluntary control) takes over, breathing may cease, without any
      overt cause being detectable, even with a thorough postmortem examination. If
      conditions are such that, at that point, the infant's body lacks the strength to
      resume breathing again under autonomic control, Sudden Infant Death Syndrome may
      result. The theory explains why infants are at greater risk if they sleep face
      down.

PMID- 14592796
TI  - The corrupted feedback hypothesis.
AB  - This paper argues that varicose veins are caused by a feedback malfunction. The
      feedback in question regulates the tone of the vein by dilating it as needed,
      using noradrenaline (NA), tapped from the circulating pool, for the purpose. The
      drug, though conventionally classified as a venoconstrictor, dilates the vein
      when it diffuses from the vasa venarum of the vein into the vein's media; the
      drug having reached the vasa by reflux from the vein lumen. A varicosity is
      created when a factor increases the volume of reflux, and, therefore, the
      quantity of NA, perfusing a unit of the vasa network, selectively. The resultant,
      exaggerated, localised, dilator effect that the NA has on a section of the vein,
      constitutes the varicosity radix. In brief, a varicosity, when first created, is
      seen as being an exaggerated, but appropriate, dilator response of a section of a
      normal vein to an inappropriate, corrupted, feedback signal. The acute varicosity
      is believed to transform into the permanent type seen in varicose veins if the
      factor responsible for it persists long enough.

PMID- 14592797
TI  - Virtual elimination of necrotising enterocolitis for 5 years - reasons?
AB  - A standardised feeding regimen was adopted in 1997 for guiding enteral feeding of
      neonates <32 weeks' gestation during clinical trials (18 months each) involving
      erythromycin (n=73) as a prokinetic and carboxymethylcellulose (n=70) as a
      laxative as well as for during 2 years (n=155) without any trials. Most aspects
      of the feeding regimen (e.g., milk increments-total volume/day, use of breast
      milk by choice, etc) were not significantly different from current practices.
      RESULTS: 298 neonates <32 weeks' gestation (<28 weeks; n=78) were enterally fed
      during the 5 years. Their demographic characteristics and median (interquartile)
      age in days at starting (AST) and days to reach full enteral feeds (FFT) of 150
      ml/kg/day were not significantly different during these 5 years: [AST: 5 (3
      7.5)], [FFT: 4 (3-7)] Only one case of definite NEC (> or =Stage II) occurred
      during the 5 years. The time to reach full feeds was also reduced by over 54%
      (including for neonates <28 weeks gestation) compared with a historical cohort.
      CONCLUSION: Sustained reduction in the time to reach full feeds with virtual
      elimination of > or =Stage II NEC for 5 years indicates continued benefits of a
      standardised feeding regimen as a simple preventive strategy to prevent NEC.
      Whether our specific policy of no enteral feeds in presence of hemodynamic
      instability associated with PDA requiring indomethacin, and/or sepsis played a
      role in achieving the significant results needs controlled trials.

PMID- 14592798
TI  - The relationship of physical and chemical processes in bone and blood formation.
AB  - An hypothesis is presented describing the relationship between the chemical and
      physical processes involved in the formation bone and blood. It is also advanced
      that blood cells are normal cells which have been disrupted by these processes
      and are therefore unstable and subject to disintegration. On the basis of the
      hypothesis conclusions are drawn concerning the connections between bone and
      blood formation and particular medical conditions. Possible means of relieving
      these conditions are advanced.

PMID- 14592799
TI  - Chromatid transport by pantographic motors (PMS).
AB  - The paper discusses a system of hinged leverages functioning as (vectorial)
      pantographic motors (PMs). Mediated by ratchets, PMs are suited for ferrying
      mammalian chromatids to mitotic antipoles. Several self-rectifying modes allow
      PMs to accurately partition genomes with minimal risk of engendering aneuploidy.

PMID- 14592800
TI  - Skeletal disorders associated with skin pigmentation: a role of melatonin?
AB  - Although frequently encountered, no available consensus about the association
      between skeletal abnormalities and skin pigmentation. Several syndromes are
      characterized by the presence of skin pigmentation in association with skeletal
      disorders like neurofibroamtosis 1, McCune-Albright Syndrome, Jaffe-Campanacci
      Syndrome and Jaffe-Lichtenstein Syndrome. Even in the absence of these syndromes,
      skeletal abnormalities were detected in all radiologically examined patients
      having patterned skin pigmentation. Although skin pigmentation is controlled by
      several factors, melatonin is the most reliable factor to have relation to
      development of skeletal abnormalities. Recent research works support that
      melatonin might play a role in bone development and several hypotheses link
      melatonin with some bone diseases associated with skin pigmentation. It seems
      that melatonin deficiency is a probable operating co-factor in a lot of clinical
      situations characterized by skin pigmentation and skeletal disorders. This would
      explain some of the un-explained observations related to these syndromes and
      research works along these lines might lead to the development of efficient
      treatment for these diseases.

PMID- 14592802
TI  - Parenchymatous pulmonary endometriosis - metastases of a low-grade endometrial
      stromal sarcoma?
AB  - Based on the data of a case of parenchymatous endometriosis of the lung in which
      three and a half years later a low-grade endometrial stromal sarcoma of the
      uterus was diagnosed the origin of this disease is discussed. The follow up of
      this patient gave the impression that the pulmonary nodules were early metastases
      of low-grade endometrial stromal sarcoma, which was initially not detected in the
      routine gynecologic examination. Furthermore, as histological and
      immunohistochemical examinations are not sufficient to distinguish reliable
      between endometriosis of the lung and pulmonary metastases from low-grade
      endometrial stromal sarcoma. In literature, in none of the few cases of
      parenchymatous pulmonary endometriosis a hysterectomy was performed to exclude a
      low-grade endometrial stromal sarcoma. Thus, parenchymatous pulmonary
      endometriosis nodules might be metastases and their occurrence should cause the
      treating physician to consider a distant metastatic spread from low-grade
      endometrial stromal sarcoma.

PMID- 14592801
TI  - Apoptotic versus genotoxic potential of anti-tumor agents: a concept of duality
      in unity.
AB  - Recent advances in anti-tumor therapy have raised a problem of secondary tumors
      and tumor resistance. Secondary tumors induced by chemotherapeutic agents as a
      consequence of primary therapy have poor prognostic outcome. Many new insights
      into molecular controls of cell cycle progression of normal and cancer cells can
      provide a useful framework in order to identify potential targets for anti-tumor
      therapies. One of the most promising strategies is the possibility to modulate
      apoptosis induced by anti-tumor agents. Cancer cell survival after chemotherapy
      will depend on specific checkpoints and/or repair pathways that have been lost,
      leading either to greater susceptibility to anti-tumor agents when the repair of
      damage is most important for survival or to greater resistance when the apoptotic
      response is more important. We have proposed a hypothesis that views survival and
      apoptotic processes (duality) in normal and tumor cells as genetically coupled
      (unity). We introduce, through a theoretical background, a new pathway of
      apoptotic inhibition. The proposed process of apoptotic inhibition is induced by
      mutation fixation in which recombination/repair processes (hRAD genes) play an
      important role. These coupled processes (duality in unity), to our view,
      underline tumor resistance by apoptotic inhibition and mutation fixation in
      normal cells exposed to anti-tumor agents.

PMID- 14592803
TI  - Winter swimming: healthy or hazardous?. Evidence and hypotheses.
AB  - Swimming in cold water during the winter season is an extreme sport, with fans
      all over the world. However, its effects on health have been debated. This
      article examines the hypothesis that the effects of winter swimming may depend on
      previous exposure to cold stimuli. Immersion in cold water in unaccustomed
      persons may lead to detrimental consequences, while, in regular winter swimmers,
      adaptive physiologic mechanisms increase tolerance to cold. Furthermore, these
      mechanisms may prevent the occurrence of a wide variety of diseases. Prospective
      studies and epidemiological data are needed to test this hypothesis.

PMID- 14592804
TI  - Vitamin C contributes to inflammation via radical generating mechanisms: a
      cautionary note.
AB  - Reactive oxygen and nitrogen species (RONS) have been ascribed an important role
      in oxidative stress contributing to the progression of inflammatory diseases such
      as Crohn's disease and rheumatoid arthritis. Redox-active metal ions such as
      Fe(II) and Cu(I) further activate RONS and thus perpetuate their damaging
      effects. High intake of ascorbic acid exerts a pro-oxidant effect by its
      interaction with metal ions via a number of established RONS generating systems.
      Caution should be exerted regarding surplus ascorbic acid intake for patients
      with chronic inflammatory diseases.

PMID- 14592805
TI  - Aids, a new hope for patients?

PMID- 14592807
TI  - All three ryanodine receptor isoforms generate rapid cooling responses in muscle
      cells.
AB  - The rapid cooling (RC) response in muscle is an increase in cytoplasmic Ca2+
      concentration ([Ca2+]i) that is probably caused by Ca2+ release from the
      sarcoplasmic reticulum (SR). However, the molecular bases of this response have
      not been completely elucidated. Three different isoforms of the SR Ca2+ release
      channels, or ryanodine receptors (RyRs), have been isolated (RyR1, RyR2, and
      RyR3). In the current investigation, the RC response was studied in RyR-null
      muscle cells (1B5) before and after transduction with HSV-1 virions containing
      the cDNAs encoding for RyR1, RyR2, or RyR3. Cells were loaded with fluo 4-AM to
      monitor changes in [Ca2+]i and perfused with either cold ( approximately 0
      degrees C), room temperature (RT), or RT buffer containing 40 mM caffeine.
      Control cells showed no significant response to cold or caffeine, whereas robust
      Ca2+ transients were recorded in response to both RC and caffeine in transduced
      cells expressing any one of the three RyR isoforms. Our data demonstrate directly
      that RyRs are responsible for the RC response and that all three isoforms respond
      in a similar manner. Ca2+ release from RyRs is likely caused by a RC-induced
      conformational change of the channel from the closed to the open state.

PMID- 14592808
TI  - FKBP12.6 and cADPR regulation of Ca2+ release in smooth muscle cells.
AB  - Intracellular Ca2+ release through ryanodine receptors (RyRs) plays important
      roles in smooth muscle excitation-contraction coupling, but the underlying
      regulatory mechanisms are poorly understood. Here we show that FK506 binding
      protein of 12.6 kDa (FKBP12.6) associates with and regulates type 2 RyRs (RyR2)
      in tracheal smooth muscle. FKBP12.6 binds to RyR2 but not other RyR or inositol
      1,4,5-trisphosphate receptors, and FKBP12, known to bind to and modulate skeletal
      RyRs, does not associate with RyR2. When dialyzed into tracheal myocytes, cyclic
      ADP-ribose (cADPR) alters spontaneous Ca2+ release at lower concentrations and
      produces macroscopic Ca2+ release at higher concentrations; neurotransmitter
      evoked Ca2+ release is also augmented by cADPR. These actions are mediated
      through FKBP12.6 because they are inhibited by molar excess of recombinant
      FKBP12.6 and are not observed in myocytes from FKBP12.6-knockout mice. We also
      report that force development in FKBP12.6-null mice, observed as a decrease in
      the concentration/tension relationship of isolated trachealis segments, is
      impaired. Taken together, these findings point to an important role of the
      FKBP12.6/RyR2 complex in stochastic (spontaneous) and receptor-mediated Ca2+
      release in smooth muscle.

PMID- 14592810
TI  - A SCL4A10 gene product maps selectively to the basolateral plasma membrane of
      choroid plexus epithelial cells.
AB  - The choroid plexus epithelium of the brain ventricular system produces the
      majority of the cerebrospinal fluid and thereby defines the ionic composition of
      the interstitial fluid in the brain. The transepithelial movement of Na+ and
      water in the choroid plexus depend on a yet-unidentified basolateral stilbene
      sensitive Na+-HCO3- uptake protein. Reverse transcriptase-polymerase chain
      reaction (RT-PCR) analysis revealed the expression in the choroid plexus of
      SLC4A10 mRNA, which encodes a stilbene-sensitive Na+-HCO3- transporter. Anti-COOH
      terminal antibodies were developed to determine the specific expression and
      localization of this Na+-HCO3- transport protein. Immunoblotting demonstrated
      antibody binding to a 180-kDa protein band from mouse and rat brain preparations
      enriched with choroid plexus. The immunoreactive band migrated as a 140-kDa
      protein after N-deglycosylation, consistent with the predicted molecular size of
      the SLC4A10 gene product. Bright-field immunohistochemistry and immunoelectron
      microscopy demonstrated strong labeling confined to the basolateral plasma
      membrane domain of the choroid plexus epithelium. Furthermore, the stilbene
      insensitive Na+-HCO3- cotransporter, NBCn1, was also localized to the basolateral
      plasma membrane domain of the choroid plexus epithelium. Hence, we propose that
      the SLC4A10 gene product and NBCn1 both function as basolateral HCO3- entry
      pathways and that the SLC4A10 gene product may be responsible for the stilbene
      sensitive Na+-HCO3- uptake that is essential for cerebrospinal fluid production.

PMID- 14592809
TI  - The mTOR/p70 S6K1 pathway regulates vascular smooth muscle cell differentiation.
AB  - Vascular smooth muscle cells (VSMC) in mature, normal blood vessels exhibit a
      differentiated, quiescent, contractile morphology, but injury induces a
      phenotypic modulation toward a proliferative, dedifferentiated, migratory
      phenotype with upregulated extracellular matrix protein synthesis (synthetic
      phenotype), which contributes to intimal hyperplasia. The mTOR (the mammalian
      target of rapamycin) pathway inhibitor rapamycin inhibits intimal hyperplasia in
      animal models and in human clinical trials. We report that rapamycin treatment
      induces differentiation in cultured synthetic phenotype VSMC from multiple
      species. VSMC treated with rapamycin assumed a contractile morphology,
      quantitatively reflected by a 67% decrease in cell area. Total protein and
      collagen synthesis were also inhibited by rapamycin. Rapamycin induced expression
      of the VSMC differentiation marker contractile proteins smooth muscle (SM) alpha
      actin, calponin, and SM myosin heavy chain (SM-MHC), as observed by
      immunoblotting and immunohistochemistry. Notably, we detected a striking
      rapamycin induction of calponin and SM-MHC mRNA, suggesting a role for mTOR in
      transcriptional control of VSMC gene expression. Rapamycin also induced
      expression of the cyclin-dependent kinase inhibitors p21(cip) and p27(kip),
      consistent with cell cycle withdrawal. Rapamycin inhibits mTOR, a signaling
      protein that regulates protein synthesis effectors, including p70 S6K1.
      Overexpression of p70 S6K1 inhibited rapamycin-induced contractile protein and
      p21(cip) expression, suggesting that this kinase opposes VSMC differentiation. In
      conclusion, we report that regulation of VSMC differentiation is a novel function
      of the rapamycin-sensitive mTOR signaling pathway.

PMID- 14592811
TI  - ATP-sensitive potassium channels mediate hyperosmotic stimulation of NKCC in slow
      twitch muscle.
AB  - In mildly hyperosmotic medium, activation of the Na+ -K+ -2Cl- cotransporter
      (NKCC) counteracts skeletal muscle cell water loss, and compounds that stimulate
      protein kinase A (PKA) activity inhibit the activation of the NKCC. The aim of
      this study was to determine the mechanism for PKA inhibition of NKCC activity in
      resting skeletal muscle. Incubation of rat slow-twitch soleus and fast-twitch
      plantaris muscles in isosmotic medium with the PKA inhibitors H-89 and KT-5720
      caused activation of the NKCC only in the soleus muscle. NKCC activation caused
      by PKA inhibition was insensitive to MEK MAPK inhibitors and to insulin but was
      abolished by the PKA stimulators isoproterenol and forskolin. Furthermore,
      pinacidil [an ATP-sensitive potassium (KATP) channel opener] or inhibition of
      glycolysis increased NKCC activity in the soleus muscle but not in the plantaris
      muscle. Preincubation of the soleus muscle with glibenclamide (a KATP channel
      inhibitor) prevented the NKCC activation by hyperosmolarity, PKA inhibition,
      pinacidil, and glycolysis inhibitors. In contrast, glibenclamide stimulated NKCC
      activity in the plantaris muscle. In cells stably transfected with the Kir6.2
      subunit of the of KATP channel, inhibition of glycolysis activated potassium
      current and NKCC activity. We conclude that activation of KATP channels in slow
      twitch muscle is necessary for activation of the NKCC and cell volume restoration
      in hyperosmotic conditions.

PMID- 14592812
TI  - Cell-specific expression of SERCA, the exogenous Ca2+ transport ATPase, in
      cardiac myocytes.
AB  - We evaluated various constructs to obtain cell-specific expression of the
      sarco(endo)plasmic reticulum Ca2+ -ATPase (SERCA) gene in cardiac myocytes after
      cDNA transfer by means of transfections or infections with adenovirus vectors.
      Expression of exogenous enhanced green fluorescent protein (EGFP) and SERCA genes
      was studied in cultured chicken embryo and neonatal rat cardiac myocytes,
      skeletal and smooth muscle cells, fibroblasts, and hepatocytes. Whereas the
      cytomegalovirus (CMV) promoter yielded high levels of protein expression in all
      cells studied, cardiac troponin T (cTnT) promoter segments demonstrated high
      specificity for cardiac myocytes. Their efficiency for protein expression was
      lower than that of the CMV promoter, but higher than that of cardiac myosin light
      chain or beta-myosin heavy chain promoter segments. A double virus system for Cre
      dependent expression under control of the CMV promoter and Cre expression under
      control of a cardiac-specific promoter yielded high protein levels in cardiac
      myocytes, but only partial cell specificity due to significant Cre expression in
      hepatocytes. Specific intracellular targeting of gene products was demonstrated
      in situ by specific immunostaining of exogenous SERCA1 and endogenous SERCA2 and
      comparative fluorescence microscopy. The -374 cTnT promoter segment was the most
      advantageous of the promoters studied, producing cell-specific SERCA expression
      and a definite increase over endogenous Ca2+ -ATPase activity as well as faster
      removal of cytosolic calcium after membrane excitation. We conclude that analysis
      of promoter efficiency and cell specificity is of definite advantage when cell
      specific expression of exogenous SERCA is wanted in cardiac myocytes after cDNA
      delivery to mixed cell populations.

PMID- 14592813
TI  - Hepatocyte growth factor induces MDCK cell morphogenesis without causing loss of
      tight junction functional integrity.
AB  - Hepatocyte growth factor (HGF) induces mitogenesis, motogenesis, and
      tubulogenesis of cultured Madin-Darby canine kidney (MDCK) epithelial cells. We
      report that in addition to these effects HGF stimulates morphogenesis of tight,
      polarized MDCK cell monolayers into pseudostratified layers without loss of tight
      junction (TJ) functional integrity. We tested TJ functional integrity during
      formation of pseudostratified layers. In response to HGF, the TJ marker ZO-1
      remained in morphologically complete rings and functional barriers to
      paracellular diffusion of ruthenium red were maintained in pseudostratified
      layers. Transepithelial resistance (TER) increased transiently two- to threefold
      during the morphogenetic transition from monolayers to pseudostratified layers
      and then declined to baseline levels once pseudostratified layers were formed. In
      MDCK cells expressing the trk/met chimera, both HGF and NGF at concentrations of
      2.5 ng/ml induced scattering. However, 2.5 ng/ml HGF did not affect TER. The peak
      effect of HGF on TER was at a concentration of 100 ng/ml. In contrast, NGF at
      concentrations as high as 25 microg/ml had no effect on TER or pseudostratified
      layer morphogenesis of trk/met-expressing cultures. These results suggest that
      altered presentation of the stimulus, such as through HGF interaction with low
      affinity sites, may change the downstream signaling response. In addition, our
      results demonstrate that HGF stimulates pseudostratified layer morphogenesis
      while inducing an increase in TER and maintaining the overall tightness of the
      epithelial layer. Stimulation of epithelial cell movements by HGF without loss of
      functional TJs may be important for maintaining epithelial integrity during
      morphogenetic events such as formation of pseudostratified epithelia, organ
      regeneration, and tissue repair.

PMID- 14592814
TI  - Expression of the AQP-1 water channel in normal human tissues: a semiquantitative
      study using tissue microarray technology.
AB  - Aquaporin water channels are a family of membrane proteins that facilitate water
      movement across biological membranes. Aquaporin-1 (AQP-1) has been found to be
      important in osmotic water movement across cell membranes of epithelial and
      endothelial barriers. However, the distribution of AQP-1 in many normal human
      tissues is still unknown. The aim of this study was to use immunohistochemistry
      and semiquantitative histomorphometric analysis to determine the tissue
      distribution and relative expression of AQP-1 in normal human tissues using
      tissue microarray (TMA) technology. The normal human TMAs employed in this study
      included cardiovascular, respiratory, gastrointestinal, hepatic and
      pancreatobiliary, oral, salivary, nasal, mammary, fetal, endocrine, genital
      tract, central and peripheral nervous systems, urinary tract, skin, cartilage,
      and other soft connective tissues. Immunohistochemistry and semiquantitative
      histomorphometric analysis confirmed the presence of AQP-1 in endothelial
      barriers of almost all tissues and in many epithelial barriers. AQP-1 was highly
      expressed in the renal cortex, choroid plexus, and pancreatic ducts. AQP-1
      expression levels were surprisingly high in the anus, gallbladder, and liver;
      moderate expression was also detected in the hippocampus and ependymal cells of
      the central nervous system. This is the first report of AQP-1 protein
      distribution in normal human TMAs. These findings confirm the presence of AQP-1
      in human endothelia and selected water-transporting epithelia and several new
      locations, including mammary epithelium, articular chondrocytes, synoviocytes,
      and synovial microvessels where AQP-1 may be involved in milk production,
      chondrocyte volume regulation, synovial fluid secretion, and homeostasis,
      respectively.

PMID- 14592815
TI  - Primary cutaneous CD8+ and CD56+ T-cell lymphomas express HLA-G and killer-cell
      inhibitory ligand, ILT2.
AB  - Primary cutaneous lymphomas constitute a spectrum of diseases characterized by a
      clonal accumulation of lymphocytes in the skin. Cutaneous T-cell lymphomas of the
      cytotoxic phenotype, including CD8+ and CD56+ lymphomas, are rare entities that
      have only been recently recognized and characterized. These lymphomas often show
      an aggressive clinical course. We investigated the expression of human leukocyte
      antigen G (HLA-G) and interleukin 10 (IL-10) in conjunction with expression of
      HLA-G killer-cell inhibitory receptor ligand immunoglobulin-like transcript 2
      (ILT2) in 3 CD56+CD4+ and 4 CD8+ cutaneous T-cell lymphomas. HLA-G expression was
      detected in 2 of 3 lymphomas of the CD56+CD4+ type and in all lymphomas of CD8+
      type. It is of note that CD56+CD4+ lymphomas displayed stronger HLA-G reactivity.
      The expression of IL-10 matched the expression of HLA-G. Together with the
      expression of IL-10, HLA-G might be one of the factors accounting for the evasion
      of immunosurveillance, thus contributing to aggressive phenotype of these
      lymphoma entities.

PMID- 14592816
TI  - Acquired somatic ATRX mutations in myelodysplastic syndrome associated with alpha
      thalassemia (ATMDS) convey a more severe hematologic phenotype than germline ATRX
      mutations.
AB  - Acquired somatic mutations in ATRX, an X-linked gene encoding a chromatin
      associated protein, were recently identified in 4 patients with the rare subtype
      of myelodysplastic syndrome (MDS) associated with thalassemia (ATMDS). Here we
      describe a series of novel point mutations in ATRX detected in archival DNA
      samples from marrow and/or blood of patients with ATMDS by use of denaturing high
      performance liquid chromatography (DHPLC), a technique sensitive to low-level
      mosaicism. Two of the new mutations result in changes in amino acids altered in
      previously described pedigrees with germ line ATRX mutations (ATR-X syndrome),
      but the hematologic abnormalities were much more severe in the patients with
      ATMDS than in the corresponding constitutional cases. In one ATMDS case where DNA
      samples from several time points were available, the proportion of ATRX-mutant
      subclones correlated with changes in the amount of hemoglobin H. This study
      strengthens the link between acquired, somatic ATRX mutations and ATMDS,
      illustrates how molecular defects associated with MDS and other hematologic
      malignancies masked by somatic mosaicism may be detected by DHPLC, and shows that
      additional factors increase the severity of the hematologic phenotype of ATRX
      mutations in ATMDS.

PMID- 14592817
TI  - Local irradiation enhances congenic donor pluripotent hematopoietic stem cell
      engraftment similarly in irradiated and nonirradiated sites.
AB  - Long-term multilineage chimerism is achieved in CD45 congenic mice receiving high
      bone marrow doses with or without mediastinal irradiation (MI). Increased donor
      chimerism results in MI-treated compared with nonirradiated animals, suggesting
      that MI makes "space" for engraftment of donor pluripotent hematopoietic stem
      cells (PHSCs). We have now examined whether space is systemic or whether
      increased engraftment of donor marrow in locally irradiated mice is confined to
      the irradiated bones. While increased donor chimerism was observed in irradiated
      bones compared with nonirradiated bones of MI-treated animals 4 weeks following
      bone marrow transplantation (BMT), these differences were minimal by 40 weeks. MI
      treated chimeras contained more adoptively transferable donor PHSCs in the marrow
      of both irradiated and distant bones compared with non-MI-treated chimeras.
      Similar proportions of donor PHSCs were present in irradiated and nonirradiated
      bones of locally irradiated mice at both 4 and 40 weeks. Irradiated bones
      contained more donor short-term repopulating cells than distant bones at 4 weeks,
      but not 40 weeks, after BMT. Our study suggests that local proliferation of donor
      PHSCs in mice receiving local irradiation rapidly leads to a systemic increase in
      donor PHSC engraftment.

PMID- 14592818
TI  - Erythrocyte detergent-resistant membrane proteins: their characterization and
      selective uptake during malarial infection.
AB  - Infection of human erythrocytes by the apicomplexan malaria parasite Plasmodium
      falciparum results in endovacuolar uptake of 4 host proteins that reside in
      erythrocyte detergent-resistant membranes (DRMs). Whether this vacuolar transport
      reflects selective uptake of host DRM proteins remains unknown. A further
      complication is that DRMs of vastly different protein and cholesterol contents
      have been isolated from erythrocytes. Here we show that isolated DRMs containing
      the highest cholesterol-to-protein ratio have low protein mass. Liquid
      chromatography, mass spectrometry, and antibody-based studies reveal that the
      major DRM proteins are band 3, flotillin-1 and -2, peroxiredoxin-2, and stomatin.
      Band 3 and stomatin, which reflect the bulk mass of erythrocyte DRM proteins, and
      all tested non-DRM proteins are excluded from the vacuolar parasite. In contrast,
      flotillin-1 and -2 and 8 minor DRM proteins are recruited to the vacuole. These
      data suggest that DRM association is necessary but not sufficient for vacuolar
      recruitment and there is active, vacuolar uptake of a subset of host DRM
      proteins. Finally, the 10 internalized DRM proteins show varied lipid and
      peptidic anchors indicating that, contrary to the prevailing model of
      apicomplexan vacuole formation, DRM association, rather than lipid anchors,
      provides the preferred criteria for protein recruitment to the malarial vacuole.

PMID- 14592820
TI  - Insulin-like growth factor 2 expressed in a novel fetal liver cell population is
      a growth factor for hematopoietic stem cells.
AB  - Hematopoietic stem cells (HSCs) undergo dramatic expansion during fetal liver
      development, but attempts to expand their numbers ex vivo have failed. We
      hypothesized that unidentified fetal liver cells produce growth factors that
      support HSC proliferation. Here we describe a novel population of CD3+ and Ter119
      day-15 fetal liver cells that support HSC expansion in culture, as determined by
      limiting dilution mouse reconstitution analyses. DNA array experiments showed
      that, among other proteins, insulin-like growth factor 2 (IGF-2) is specifically
      expressed in fetal liver CD3+ cells but not in several cells that do not support
      HSCs. Treatment of fetal liver CD3+Ter119- cells with anti-IGF-2 abrogated their
      HSC supportive activity, suggesting that IGF-2 is the key molecule produced by
      these cells that stimulates HSC expansion. All mouse fetal liver and adult bone
      marrow HSCs express receptors for IGF-2. Indeed, when combined with other growth
      factors, IGF-2 supports a 2-fold expansion of day-15 fetal liver Lin-Sca-1+c-Kit+
      long-term (LT)-HSC numbers. Thus, fetal liver CD3+Ter119- cells are a novel
      stromal population that is capable of supporting HSC expansion, and IGF-2,
      produced by these cells, is an important growth factor for fetal liver and, as we
      show, adult bone marrow HSCs.

PMID- 14592819
TI  - Adult stem cells from bone marrow (MSCs) isolated from different strains of
      inbred mice vary in surface epitopes, rates of proliferation, and differentiation
      potential.
AB  - For reasons that are not apparent, it has been difficult to isolate and expand
      the adult stem cells referred to as mesenchymal stem cells or marrow stromal
      cells (MSCs) from murine bone marrow. We developed a protocol that provides
      rapidly expanding MSCs from 5 strains of inbred mice. The MSCs obtained from 5
      different strains of mice were similar to human and rat MSCs in that they
      expanded more rapidly if plated at very low density, formed single-cell-derived
      colonies, and readily differentiated into either adipocytes, chondrocytes, or
      mineralizing cells. However, the cells from the 5 strains differed in their media
      requirements for optimal growth, rates of propagation, and presence of the
      surface epitopes CD34, stem cell antigen-1 (Sca-1), and vascular cell adhesion
      molecule 1 (VCAM-1). The protocol should make it possible to undertake a large
      number of experiments with MSCs in transgenic mice that have previously not been
      possible. The differences among MSCs from different strains may explain some of
      the conflicting data recently published on the engraftment of mouse MSCs or other
      bone marrow cells into nonhematopoietic tissues.

PMID- 14592821
TI  - Vav1: an oncogene that regulates specific transcriptional activation of T cells.
AB  - The nuclear factor of activated T cells (NFAT) proteins are a family of
      transcription factors whose activation is controlled by calcineurin, a Ca2+
      dependent phosphatase. Once dephosphorylated, these proteins move to the nucleus
      where they interact with cofactors to form transcription factor complexes.
      Inhibition of NFAT proteins by immunosuppressants, such as cyclosporin A (CsA)
      and FK506, is used clinically to prevent transplant rejection. Although these
      drugs have revolutionized organ transplantation, their use is associated with
      severe side effects in other organs in which NFAT proteins are important. One of
      the signal transducers that controls NFAT activity is Vav1, which is exclusively
      expressed in the hematopoietic system. Vav1 contains numerous modular domains
      that enable its function as a guanine exchange factor (GEF) toward RhoGTPases as
      well as participate in protein-protein interactions. This review focuses on the
      mechanisms by which Vav1 regulates NFAT through GEF-dependent and -independent
      cascades, emphasizing the newly assigned role of Vav1 in the regulation of Ca2+
      release. Because of its restriction to hematopoietic cell lineages and its
      importance in the regulation of NFAT, targeting Vav1 and, in particular, its
      association with other proteins may offer a highly selective means of modifying T
      cell behavior, thus allowing the development of more specific immunosuppressive
      therapies.

PMID- 14592822
TI  - Novel heat shock protein Hsp70L1 activates dendritic cells and acts as a Th1
      polarizing adjuvant.
AB  - Heat shock proteins (HSPs) are reported to act as effective adjuvants to elicit
      anti-tumor and anti-infection immunity. Here, we report that Hsp70-like protein 1
      (Hsp70L1), a novel HSP derived from human dendritic cells (DCs), has potent
      adjuvant effects that polarize responses toward Th1. With a calculated molecular
      weight of 54.8 kDa, Hsp70L1 is smaller in size than Hsp70 but resembles it both
      structurally and functionally. Hsp70L1 shares common receptors on DCs with Hsp70
      and can interact with DCs, promoting DC maturation and stimulating secretion of
      the proinflammatory cytokines interleukin 12p70 (IL-12p70), IL-1beta, tumor
      necrosis factor-alpha (TNF-alpha), and the chemokines IP-10, macrophage
      inflammatory protein-1alpha (MIP-1alpha), MIP-1beta, and normal T cell expressed
      and secreted (RANTES). The induction of interferon-gamma-inducible protein 10 (IP
      10) secretion by Hsp70L1 is not shared by Hsp70, and other functional differences
      include more potent stimulation of DC IL-12p70, CC-chemokine, and CCR7 and CXCR4
      expression by Hsp70L1. Immunization of mice with the hybrid peptide Hsp70L1
      ovalbumin(OVA)(257-264) induces an OVA(257-264)-specific Th1 response and
      cytotoxic T lymphocyte (CTL) that results in significant inhibition of E.G7-OVA
      tumor growth. The ability of Hsp70L1 to activate DCs indicates its potential as a
      novel adjuvant for use with peptide immunizations; the Hsp70L1 antigen peptide
      hybrid may serve as a more effective vaccine for the control of cancer and
      infectious diseases.

PMID- 14592823
TI  - Platelet factor 4 (PF-4)-induced neutrophil adhesion is controlled by src
      kinases, whereas PF-4-mediated exocytosis requires the additional activation of
      p38 MAP kinase and phosphatidylinositol 3-kinase.
AB  - Among the various chemokines that are functionally active on neutrophils,
      platelet factor 4 (PF-4; CXCL4) appears to have a specialized role. Lacking
      typical chemokine activities, PF-4 stimulates neutrophils to undergo firm
      adhesion to endothelial cells and, in the presence of an appropriate costimulus
      like tumor necrosis factor (TNF), PF-4 induces exocytosis of secondary granule
      contents. Analyzing the individual contribution of PF-4 and its costimuli in the
      control of these functions at the signaling level, we demonstrate that TNF
      induced activation of p38 mitogen-activated protein (MAP) kinase (but not
      extracellular regulated kinase [Erk] kinases) acts as general and essential
      costimulatory signal in PF-4-dependent neutrophil exocytosis. This was shown by
      the use of a specific inhibitor (SB203580), by biologic (lipopolysaccharide, N
      formyl-methionyl-leucyl-phenylalanine) and pharmacologic (anisomycin) activators
      of p38 MAP kinase, and by phosphorylation studies. Furthermore, TNF-mediated
      activation of phosphatidylinositol 3-kinase (PI 3-kinase) represents an
      additional essential signaling component in this process as demonstrated by
      studies with its inhibitor wortmannin as well as by analysis of the
      phosphorylation of AKT kinase. PF-4, however, directly activates src-kinases and
      PF-4-induced adherence as well as PF-4/TNF-mediated exocytosis was inhibited by
      an src-kinase inhibitor PP1. Taken together, neutrophil exocytosis and adherence
      are regulated on p38 MAP kinase, PI 3-kinase, and src-kinase activation.

PMID- 14592824
TI  - A neutralizing monoclonal antibody (mAb A24) directed against the transferrin
      receptor induces apoptosis of tumor T lymphocytes from ATL patients.
AB  - Adult T-cell leukemia/lymphoma (ATL) is an aggressive lymphoid proliferative
      disease that exists under diverse clinical forms ranging from chronic to acute.
      Although leukemic cells from patients with ATL exhibit an intrinsic resistance to
      chemotherapy, monoclonal antibodies directed against CD25 (interleukin 2 receptor
      alpha [IL-2Ralpha] antibody) have been used as specific therapeutic agents.
      However, significant clinical results with these antibodies have been
      demonstrated only in chronic forms of ATL. In contrast to resting T cells, human
      T-cell lymphotropic virus type 1 (HTLV-1)-infected cells constitutively express
      high levels of surface transferrin receptor (TfR). Herein, we report the
      characterization of a new monoclonal antibody (mAb A24) directed against the
      human TfR and the evaluation of its capacity to block the proliferation of ATL
      cells ex vivo. We determined that A24 binds TfR with an equilibrium constant
      (K'd) of 2.7 nM and competes with transferrin for binding to TfR. A24 also
      inhibited [55Fe]-transferrin uptake in activated T cells and blocked T-cell
      proliferation. Moreover, A24 reduced and impaired TfR expression and recycling,
      respectively. Most important, we showed that A24 blocked the ex vivo
      proliferation of malignant T cells from both acute and chronic forms of ATL,
      through induction of programmed cell death. Therefore efficient therapeutic tools
      to treat acute forms of ATL might be derived from A24.

PMID- 14592825
TI  - Recombinant factor VIIa restores aggregation of alphaIIbbeta3-deficient platelets
      via tissue factor-independent fibrin generation.
AB  - Recombinant factor VIIa (rFVIIa) is a safe and effective prohemostatic drug for
      patients with Glanzmann thrombasthenia (GT). However, the mechanism of action of
      rFVIIa in these patients is still unclear. Although patients with GT are
      characterized by a complete absence of platelet aggregation to a variety of
      agonists, it has been shown that GT platelets are able to form aggregates,
      provided polymerizing fibrin is present. We studied the effect of rFVIIa-mediated
      fibrin formation on aggregation of alphaIIbbeta3-deficient platelets. When washed
      platelets from GT patients or platelets from healthy volunteers treated with an
      arginyl-glycyl-aspartyl-containing peptide were activated with collagen in the
      presence of rFVIIa and purified coagulation factors X, II, and fibrinogen,
      complete aggregation occurred after a lag phase. Fibrin generation proceeded via
      rFVIIa-mediated thrombin generation on the activated platelet surface
      independently of tissue factor. Electron microscopic analysis of alphaIIbbeta3
      independent platelet aggregates showed a densely packed structure suggestive of a
      true platelet-fibrin interaction and not via trapping of platelets into a fibrin
      network. Also, rFVIIa-mediated alphaIIbbeta3-independent aggregation was
      demonstrated under conditions of flow using a collagen-coated surface. In
      conclusion, the efficacy of rFVIIa in GT patients might be explained by induction
      of alphaIIbbeta3-independent platelet aggregation, which compensates the lack of
      alphaIIbbeta3-dependent aggregation.

PMID- 14592826
TI  - Receptor synergy of interleukin-6 (IL-6) and insulin-like growth factor-I in
      myeloma cells that highly express IL-6 receptor alpha [corrected].
AB  - Interleukin-6 (IL-6) is a growth and antiapoptotic factor for human myeloma
      cells. The autocrine loop and increased expression of the growth factor receptors
      have been postulated as the mechanisms of tumorigenesis. Here we show that IL-6
      stimulation induced the phosphorylation of insulin-like growth factor-I (IGF-I)
      receptors in a human myeloma cell line, NOP2, highly expressing IL-6 receptor
      alpha (IL-6R alpha) and in the IL-6R alpha-transfected U266 cell line. IL-6
      dependent complex formation of IL-6R alpha with IGF-I receptor beta was found in
      NOP2 where IL-6R alpha colocalized with IGF-I receptors at lipid rafts. Moreover,
      the IL-6-induced phosphorylation of IGF-I receptor beta was not blocked by a
      Janus kinase 2 (Jak2) inhibitor. In addition to the activation of the signal
      transducer and activator of transcription 3 and extracellular signal-regulated
      kinase 1/2, IL-6 stimulation led to the activation of Akt, presumably following
      the phosphorylation of IGF-I receptors. Thus, our results suggest that in NOP2,
      IL-6R alpha and IGF-I receptors exist on the plasma membrane in close proximity,
      facilitating the efficient assembly of 2 receptors in response to IL-6. The
      synergistic effects of highly expressed IL-6R alpha on IGF-I receptor-mediated
      signals provide a novel insight into the Jak-independent IL-6 signaling mechanism
      of receptor cross-talk in human myeloma cells.

PMID- 14592827
TI  - Overexpression of IL-7R alpha provides a competitive advantage during early T
      cell development.
AB  - Critical checkpoints controlling early thymic T-cell development and homeostasis
      are set by the proper signaling function of the interleukin 7 receptor (IL-7R)
      and the pre-T-cell antigen receptor. Although alpha beta T-cell development is
      observed in IL-7- and IL-7R alpha-deficient mice, the number of thymocytes is
      significantly reduced, implying a role for the IL-7R in controlling the size of
      the thymic T-cell compartment. Here, we report the overexpression of IL-7R alpha
      that occurs in the early T-cell compartment from AKR/J mice, animals that are
      highly susceptible to the spontaneous development of thymoma. Increased IL-7R
      alpha was revealed by surface staining, and increased IL-7R alpha mRNA was
      documented by using reverse transcriptase-polymerase chain reaction (RT-PCR).
      This resulted in increased survival of AKR/J early thymocytes, shown by the
      decreased frequency of TUNEL(+) (terminal deoxynucleotidyl transferase mediated
      deoxyuridine triphosphate [dUTP]-fluorescein nick end labeling) cells. In an in
      vivo thymocyte repopulation model, AKR/J thymocytes had a selective advantage
      over healthy thymocytes. This advantage occurred at early stages of T-cell
      development. Our findings support the model that overexpression of growth factor
      receptors can contribute to proliferation and malignancy.

PMID- 14592828
TI  - Thrombomodulin mutant mice with a strongly reduced capacity to generate activated
      protein C have an unaltered pulmonary immune response to respiratory pathogens
      and lipopolysaccharide.
AB  - The thrombomodulin-protein C-protein S (TM-PC-PS) pathway exerts anticoagulant
      and anti-inflammatory effects. We investigated the role of TM in the pulmonary
      immune response in vivo by the use of mice with a mutation in the TM gene
      (TM(pro/pro)) that was earlier found to result in a minimal capacity for
      activated PC (APC) generation in the circulation. We here demonstrate that
      TM(pro/pro) mice also display a strongly reduced capacity to produce APC in the
      alveolar compartment upon intrapulmonary delivery of PC and thrombin. We
      monitored procoagulant and inflammatory changes in the lung during Gram-positive
      (Streptococcus pneumoniae) and Gram-negative (Klebsiella pneumoniae) pneumonia
      and after local administration of lipopolysaccharide (LPS). Bacterial pneumonia
      was associated with fibrin(ogen) depositions in the lung that colocalized with
      inflammatory infiltrates. LPS also induced a rise in thrombin-antithrombin
      complexes in bronchoalveolar lavage fluid. These pulmonary procoagulant responses
      were unaltered in TM(pro/pro) mice, except for enhanced fibrin(ogen) deposition
      during pneumococcal pneumonia. In addition, TM(pro/pro) mice displayed unchanged
      antibacterial defense, neutrophil recruitment, and cytokine/chemokine levels.
      These data suggest that the capacity of TM to generate APC does not play a role
      of importance in the pulmonary response to respiratory pathogens or LPS.

PMID- 14592829
TI  - Thymosin beta 4 induces the synthesis of plasminogen activator inhibitor 1 in
      cultured endothelial cells and increases its extracellular expression.
AB  - Thymosin beta 4(T beta 4), a 4.9-kDa polypeptide primarily known as a main G
      actin-sequestering peptide, is present in high concentrations in various cells
      and in the circulation. We have found that T beta 4 upregulates the expression of
      plasminogen activator inhibitor 1 (PAI-1) in endothelial cells measured both at
      the level of mRNA and protein synthesis. This effect seems to be cell specific
      and was not observed when other cells such as human fibroblasts, PC3, and U937
      were tested. T beta 4 significantly activated the PAI-1 promoter in EA.hy 926
      cells transiently transfected either with plasmid p800LUC containing PAI-1
      promoter fragment (-800 to +71) or the PAI-1 promoter linked with green
      fluorescent protein. T beta 4 mediated up-regulation of PAI-1 involved activation
      of the mitogen-activated protein kinase cascade. Furthermore, T beta 4 enhanced c
      Fos/c-Jun DNA-binding activity to the activator protein 1 (AP-1)-like element (
      59 to -52). The specificity of this binding activity was demonstrated by
      competition electrophoretic mobility shift assay and after transfection of EA.hy
      926 cells with the mutated PAI-1 promoter. Taken together, these data indicate
      that, in response to T beta 4 stimulation, AP-1 activity increases to enhance PAI
      1 transcription through its unique AP-1-like element at -59 to -52 in the PAI-1
      promoter.

PMID- 14592830
TI  - Inhibition of restenosis by tissue factor pathway inhibitor: in vivo and in vitro
      evidence for suppressed monocyte chemoattraction and reduced gelatinolytic
      activity.
AB  - Activation of inflammatory and procoagulant mechanisms is thought to contribute
      significantly to the initiation of restenosis, a common complication after
      balloon angioplasty of obstructed arteries. During this process, expression of
      tissue factor (TF) represents one of the major physiologic triggers of
      coagulation that results in thrombus formation and the generation of additional
      signals leading to vascular smooth muscle cell (VSMC) proliferation and
      migration. In this study, we have investigated the mechanisms by which inhibition
      of coagulation at an early stage through overexpression of tissue factor pathway
      inhibitor (TFPI), an endogenous inhibitor of TF, might reduce restenosis. In a
      rabbit femoral artery model, percutaneous delivery of TFPI using a recombinant
      adenoviral vector resulted in a significant reduction of the intimamedia ratio 21
      days after injury. Investigating several markers of inflammation and coagulation,
      we found reduced neointimal expression of monocyte chemoattractant protein-1 (MCP
      1), lesional monocyte infiltration, and expression of vascular TF, matrix
      metalloproteinase-2 (MMP-2), and MMP-9. Moreover, overexpression of TFPI
      suppressed the autocrine release of platelet-derived growth factor BB (PDGF-BB),
      MCP-1, and MMP-2 in response to factors VIIa and Xa from VSMCs in vitro and
      inhibited monocyte TF activity. These results suggest that TFPI exerts its action
      in vivo through not only thrombotic, but also nonthrombotic mechanisms.

PMID- 14592831
TI  - Thiol/disulfide exchange is a prerequisite for CXCR4-tropic HIV-1 envelope
      mediated T-cell fusion during viral entry.
AB  - Attachment of gp120 to CD4 during HIV-1 entry triggers structural rearrangement
      in gp120 that enables binding to an appropriate coreceptor. Following coreceptor
      engagement, additional conformational changes occur in the envelope (Env),
      resulting in fusion of virion and cell membranes. Catalysts with redox-isomerase
      activity, such as protein disulfide isomerase (PDI), facilitate Env conversion
      from its inactive to its fusion-competent conformation. We report here that anti
      PDI agents effectively block CXCR4 Env-mediated fusion and spread of virus
      infection. Exogenously added PDI, in turn, can rescue fusion from this blockade.
      We further find that PDI facilitates thiol/disulfide rearrangement in gp120
      during conformational change, whereas inhibition of this redox shuffling prevents
      gp41 from assuming the fusogenic 6-helix bundle conformation. At the virus-cell
      contact site, gp120 induces assembly of PDI, CD4, and CXCR4 into a tetramolecular
      protein complex serving as a portal for viral entry. Our findings support the
      hypothesis that Env conformational change depends on a well-coordinated action of
      a tripartite system in which PDI works in concert with the receptor and the
      coreceptor to effectively lower the activation energy barrier required for Env
      conformational rearrangement.

PMID- 14592832
TI  - Primary diffuse large B-cell lymphomas of the central nervous system are targeted
      by aberrant somatic hypermutation.
AB  - We have addressed whether aberrant ongoing hypermutation can be detected in the
      proto-oncogenes PIM1, c-MYC, RhoH/TTF, PAX5, and the tumor-suppressor gene CD95
      in primary central nervous system lymphomas (PCNSLs) derived from immunocompetent
      HIV-negative patients. Nine of 10 PCNSLs analyzed harbored somatic mutations in
      the PIM1, c-MYC, RhoH/TTF, and PAX5 genes, but not in the CD95 gene, with 8
      tumors carrying alterations in at least 2 of these genes. Furthermore, ongoing
      aberrant mutation was evidenced in a subset of PCNSLs (2 of 3). Although most of
      the mutations corresponded to base pair substitutions, deletions were also
      present. The mean mutation frequency was approximately 60-fold lower for these
      genes compared with the values obtained for immunoglobulin genes in PCNSL. They
      were increased 2- to 5-fold compared with extracerebral diffuse large B-cell
      lymphoma (DLBCL). In summary, our data demonstrate aberrant somatic
      hypermutations at high frequency in the PIM1, PAX5, RhoH/TTF, and c-MYC genes in
      most PCNSLs. These findings may indicate a pathogenic role for aberrant somatic
      hypermutation in PCNSL development. In contrast, although mutations were detected
      in exon 9 of the CD95 gene, the lack of mutations in the 5' region provides no
      evidence for the CD95 gene as a target for aberrant somatic mutation.

PMID- 14592833
TI  - The variable number of tandem repeat polymorphism of platelet glycoprotein
      Ibalpha and risk of coronary heart disease.
AB  - Glycoprotein (GP) Ib-IX-V complex plays an important role in formation of
      platelet-fibrin clot at the area of damaged vessel wall. One polymorphism of GP
      Ibalpha, the main component of GP Ib-IX-V complex, is due to variable numbers of
      tandem repeats (VNTRs) in the macroglycopeptide region of this molecule. We
      studied the association between the presence of different VNTR alleles of GP
      Ibalpha and the frequency of coronary heart disease (CHD) among individuals
      recruited to a large community-based case-cohort study (Atherosclerosis Risk in
      Communities [ARIC] study). We found that the distribution of VNTR alleles of GP
      Ibalpha is different among whites and African Americans. The B allele (with 3
      repeats) of GP Ibalpha is relatively more common among African Americans compared
      with whites. In African Americans, the CC genotype (homozygous with 2 repeats) is
      associated with a lower risk of CHD events than all other genotypes.

PMID- 14592834
TI  - Cotransplantation of third-party mesenchymal stromal cells can alleviate single
      donor predominance and increase engraftment from double cord transplantation.
AB  - Although the infusion of umbilical cord blood (UCB) from multiple donors can be a
      strategy to overcome the cell dose limitation frequently encountered in UCB
      transplantation, clinical trials have revealed that cells from one donor dominate
      engraftment. To investigate the origin of and the factors influencing this
      inequality, we performed mixed transplantation of 2 UCB units with varying
      degrees of HLA disparities into NOD/SCID mice and determined donor origins by
      polymerase chain reaction-sequence-specific oligonucleotide probe (PCR-SSOP) or
      real-time quantitative (RQ)-PCR for human short tandem repeats (STRs). When total
      mononuclear cells from 2 units were transplanted as a mixture, cells from one
      donor predominated (ratio, 81:19), despite comparable overall engraftment when
      infused as single units, and no augmentation in overall engraftment was observed
      when compared with the single-unit controls. However, lineage depletion or
      cotransplantation of mesenchymal stromal cells (MSCs) expanded from third-party
      bone marrow resulted in more balanced coengraftment. Direct comparison of double
      UCB transplantation in the presence or absence of MSCs showed that the reduced
      deviation in the donor ratio (1.8:1 vs. 2.8:1) correlated with a higher overall
      level of engraftment with MSC cotransplantation. These results indicate that
      third-party MSCs can be used to alleviate donor deviation and to facilitate
      engraftment of multidonor UCB.

PMID- 14592835
TI  - A signaling mechanism for growth-related expression of fetal hemoglobin.
AB  - Increases in fetal hemoglobin have been identified after birth in several
      clinical settings associated with stressed or malignant erythropoiesis. To better
      understand the relationship between the expression of this fetal protein and
      growth, donated human erythroid progenitor cells were cultured in the presence of
      erythropoietin (EPO) plus the growth-modifying cytokine stem cell factor (SCF),
      and several growth-related signaling pathways were interrogated. Only the MEK1/2
      inhibitor (PD98059) demonstrated significant effects on fetal hemoglobin. In the
      absence of PD98059, levels of fetal hemoglobin averaged 27.4% +/- 7.9% in EPO+SCF
      compared with 1.26% +/- 1.7% in EPO alone (P =.02). A linear dose response in
      levels of fetal hemoglobin to PD98059 was detected (0.16 microM = 27.13%, 0.8
      microM = 19.6%, 4 microM = 12.2%, 20 microM = 1.54%). Western blot analyses
      revealed that SCF was required for phosphorylation of MEK and p44MAPK in this
      setting, and quantitative polymerase chain reaction demonstrated a significant
      increase in gamma-globin mRNA. Particular perturbations of growth-related
      signaling may also function to activate tissue-specific genes normally expressed
      during fetal development. This concept may be relevant for the development of new
      treatment rationales for beta hemoglobinopathies.

PMID- 14592836
TI  - Pregnancy induces minor histocompatibility antigen-specific cytotoxic T cells:
      implications for stem cell transplantation and immunotherapy.
AB  - Recipients of HLA-identical stem cell transplants have a poorer transplant
      outcome if the donor is female rather than male. We analyzed whether pregnancy
      primes for minor histocompatibility (H) antigens. Peripheral blood mononuclear
      cells (PBMCs) from healthy multiparous female blood donors were depleted for
      CD4+, CD14+, CD16+, and CD19+ cells, stained with minor H antigen-specific HLA-A2
      tetramers, sorted by fluorescence-activated cell sorting, and tested for
      cytotoxic activity. Minor H antigens HY-, HA-1-, and HA-2-specific cytotoxic T
      cells (CD8+, CD45RA-) were present in PBMCs from 4 of 7 female donors up to 22
      years after the last delivery. Interestingly, in 2 of the 4 cases microchimerism
      of the putative immunizing minor H antigen was observed. Thus, pregnancy can lead
      to alloimmune responses against the infant's paternal minor H antigens. The minor
      H antigen immunization status of female donors raises important questions for the
      clinical practice of stem cell transplantation.

PMID- 14592837
TI  - CCL19/CCL21-triggered signal transduction and migration of dendritic cells
      requires prostaglandin E2.
AB  - The control of dendritic cell (DC) migration is pivotal for the initiation of
      cellular immune responses. When activated with inflammatory stimuli, the
      chemokine receptor CCR7 is up-regulated on DCs. Activated DCs home to lymphoid
      organs, where the CCR7 ligands CCL19 and CCL21 are expressed. We previously found
      that human monocyte-derived DCs (MoDCs) exclusively migrated to CCL19 and CCL21
      when matured in the presence of prostaglandin (PG) E2. Because PGE2 did not alter
      CCR7 cell surface expression, we examined whether PGE2 may exert its effect by
      coupling CCR7 to signal transduction modules. Indeed, stimulation with CCR7
      ligands led to enhanced phosphatidylinositol-3-kinase-mediated phosphorylation of
      protein kinase B when MoDCs were matured in the presence of PGE2. Moreover,
      CCL19/CCL21-induced intracellular calcium mobilization in MoDCs occurred only
      when PGE2 was present during maturation. MoDC migration to CCL19 and CCL21 was
      dependent on phospholipase C and intracellular calcium flux but not on
      phosphatidylinositol-3 kinase. Hence, our data provide insight into CCL19/CCL21
      triggered signal transduction pathways and identify a novel function for PGE2 in
      controlling the migration of mature MoDCs by facilitating CCR7 signal
      transduction.

PMID- 14592838
TI  - High levels of osteopontin associated with polymorphisms in its gene are a risk
      factor for development of autoimmunity/lymphoproliferation.
AB  - The autoimmune/lymphoproliferative syndrome (ALPS) displays defective function of
      Fas, autoimmunities, lymphadenopathy/splenomegaly, and expansion of CD4/CD8
      double-negative (DN) T cells. Dianzani autoimmune/lymphoproliferative disease
      (DALD) is an ALPS variant lacking DN cells. Both forms have been ascribed to
      inherited mutations hitting the Fas system but other factors may be involved. A
      pilot cDNA array analysis on a DALD patient detected overexpression of the
      cytokine osteopontin (OPN). This observation was confirmed by enzyme-linked
      immunosorbent assay (ELISA) detection of higher OPN serum levels in DALD patients
      (n = 25) than in controls (n = 50). Analysis of the OPN cDNA identified 4
      polymorphisms forming 3 haplotypes (A, B, and C). Their overall distribution and
      genotypic combinations were different in patients (N = 26) and controls (N = 158)
      (P <.01). Subjects carrying haplotype B and/or C had an 8-fold higher risk of
      developing DALD than haplotype A homozygotes. Several data suggest that these
      haplotypes influence OPN levels: (1) in DALD families, high levels cosegregated
      with haplotype B or C; (2) in healthy controls, haplotype B or C carriers
      displayed higher levels than haplotype A homozygotes; and (3) in AB and AC
      heterozygotes, mRNA for haplotype B or C was more abundant than that for
      haplotype A. In vitro, exogenous OPN decreased activation-induced T-cell death,
      which suggests that high OPN levels are involved in the apoptosis defect.

PMID- 14592839
TI  - Syndecan-2 is essential for angiogenic sprouting during zebrafish development.
AB  - We used a morpholino-based gene-targeting screen to identify a novel protein
      essential for vascular development using the zebrafish, Danio rerio. We show that
      syndecan-2, a cell-surface heparan sulfate proteoglycan, is essential for
      angiogenic sprouting during embryogenesis. The vascular function of syndecan-2 is
      likely conserved, as zebrafish and mouse syndecan-2 show similar expression
      patterns around major trunk vessels, and human syndecan-2 can restore angiogenic
      sprouting in syndecan-2 morphants. In contrast, forced expression of a truncated
      form of syndecan-2 results in embryos with defects in angiogenesis, indicating
      that the highly conserved cytoplasmic tail is important for the vascular function
      of syndecan-2. We further show that vascular endothelial growth factor (VEGF) and
      syndecan-2 genetically interact in vivo using both gain-of-function and loss-of
      function studies in zebrafish. VEGF-mediated ectopic signaling is compromised in
      syndecan-2 morphants, and ectopic syndecan-2 potentiates ectopic VEGF signaling.
      Syndecan-2 as a novel angiogenic factor is a potential candidate for use in the
      development of angiogenesis-based therapies.

PMID- 14592840
TI  - Adhesion to E-selectin promotes growth inhibition and apoptosis of human and
      murine hematopoietic progenitor cells independent of PSGL-1.
AB  - Although both P- and E-selectin are constitutively expressed on bone marrow
      endothelial cells, their role in the regulation of hematopoiesis has only
      recently been investigated. We have previously shown that P-selectin glycoprotein
      ligand-l (PSGL-1/CD162) is expressed by primitive human bone marrow CD34+ cells,
      mediates their adhesion to P-selectin, and, more importantly, inhibits their
      proliferation. We now demonstrate that adhesion to E-selectin inhibits the
      proliferation of human CD34+ cells isolated either from human umbilical cord
      blood, adult mobilized blood, or steady-state bone marrow. Furthermore, a
      subpopulation, which does not contain the most primitive hematopoietic progenitor
      cells, undergoes apoptosis following E-selectin-mediated adhesion. The same
      phenomenon was observed in cells isolated from mouse bone marrow. Using lineage
      negative Sca-1+ c-KIT+ bone marrow cells from PSGL-1(-/-) and wild-type mice, we
      establish that PSGL-1 is not the ligand involved in E-selectin-mediated growth
      inhibition and apoptosis. Moreover, stable transfection of the human myeloid cell
      line K562 (which does not express PSGL-1) with alpha(1,3) fucosyltransferase VII
      alone was sufficient to recapitulate the E-selectin-mediated growth inhibition
      and apoptosis observed in hematopoietic progenitor cells. These data demonstrate
      that an E-selectin ligand(s) other than PSGL-1 transduces growth inhibitory and
      proapoptotic signals and requires posttranslational fucosylation to be
      functional.

PMID- 14592841
TI  - Internal tandem duplication mutation of FLT3 blocks myeloid differentiation
      through suppression of C/EBPalpha expression.
AB  - Constitutively activating mutations of FMS-like tyrosine kinase 3 (FLT3) occur in
      approximately one third of patients with acute myeloid leukemia (AML) and are
      associated with poor prognosis. Altered FLT3 signaling leads to antiapoptotic and
      proliferative signaling pathways. We recently showed that these mutations can
      also contribute to the differentiation arrest that characterizes leukemia. In
      this report we investigated the mechanism by which internal tandem duplication
      (ITD) mutation of FLT3 signaling blocks differentiation. Normally, myeloid
      differentiation requires the induction of CCAAT/enhancer-binding protein alpha
      (C/EBPalpha) and PU.1 expression. Expression of both genes was repressed by
      FLT3/ITD signaling in 32Dcl3 (32D) cells and this repression was overcome by
      treatment with a FLT3 inhibitor, allowing differentiation to proceed. We also
      observed increased expression of C/EBPalpha and PU.1 accompanied by signs of
      differentiation in 2 of 3 primary AML samples from patients with FLT3/ITD
      mutations receiving a FLT3 inhibitor, CEP-701, as part of a clinical trial.
      Forced expression of C/EBPalpha was also able to overcome FLT3/ITD-mediated
      differentiation block, further proving the importance of C/EBPalpha in this
      process.

PMID- 14592842
TI  - Long-term inhibition of Rho-kinase suppresses neointimal formation after stent
      implantation in porcine coronary arteries: involvement of multiple mechanisms.
AB  - OBJECTIVE: We recently demonstrated that Rho-kinase, an effector of the small
      GTPase Rho, is substantially involved in the pathogenesis of arteriosclerosis. In
      this study, we examined whether Rho-kinase is also involved in in-stent
      restenosis and if so, what mechanism is involved. METHODS AND RESULTS: Pigs
      underwent stent implantation in the left coronary artery with or without
      administration of fasudil (30 mg/kg per day orally), a specific Rho-kinase
      inhibitor, starting 2 days before the procedure for a duration of 4 weeks. On day
      28, reductions in coronary diameter and neointimal formation associated with
      macrophage accumulation, collagen deposition, and transforming growth factor
      (TGF)-beta1 expression were noted at the stent site, and all were significantly
      suppressed by fasudil. On day 7, fasudil significantly increased the frequency of
      TUNEL-positive apoptotic cells, while it tended to reduce that of
      bromodeoxyuridine-positive proliferating cells in the neointima. Western blot
      analysis on day 7 demonstrated that phosphorylations of the ezrin/radixin/moesin
      family (a marker of Rho-kinase activity in vivo) and protein expression of
      monocyte chemoattractant protein-1and bcl-2 were upregulated at the stent site
      and were significantly suppressed by fasudil. CONCLUSIONS: These results indicate
      that long-term inhibition of Rho-kinase suppresses in-stent neointimal formation
      by multiple mechanisms, including reduced vascular inflammation, enhanced
      apoptosis, and decreased collagen deposition.

PMID- 14592843
TI  - Quantitative trait locus mapping of genes that regulate phospholipid transfer
      activity in SM/J and NZB/BlNJ inbred mice.
AB  - OBJECTIVE: Phospholipid transfer protein (PLTP), an important protein in the
      transfer of phospholipids between lipoprotein particles and in the remodeling of
      HDL, is regulated at both the transcriptional and the protein level. We performed
      quantitative trait locus (QTL) analysis to identify genomic loci regulating PLTP
      activity in mice. METHODS AND RESULTS: Plasma PLTP activity was measured in 217
      male F2 progeny from a SM/J x NZB/B1NJ intercross. Two QTL for plasma PLTP
      activity in mice fed chow (Pltpq1 and Pltpq2) were found on chromosomes 3 (34 cM,
      logarithm of odds [LOD] 3.5) and 10 (66 cM, LOD 4.1); two additional QTL in mice
      fed atherogenic diet (Pltpq3 and Pltpq4) were found on chromosomes 9 (56 cM, LOD
      4.5) and 15 (34 cM, LOD 5.0); and one QTL (Pltiq1) for the inducibility of PLTP
      activity was found on chromosome 4 (70 cM, LOD 3.7). Several candidate genes for
      these 5 QTL were tested by sequence comparison and expression studies.
      CONCLUSIONS: We identified five significant loci involved in PLTP activity in the
      mouse and provided supporting evidence for the candidacy of Nr1h4 and Apof as the
      genes underlying Pltpq2.

PMID- 14592844
TI  - Upregulation of vascular extracellular superoxide dismutase in patients with
      acute coronary syndromes.
AB  - OBJECTIVE: We examined the vascular expression levels of extracellular superoxide
      dismutase (EC-SOD), a major antioxidant enzyme in the cardiovascular system, in
      patients with acute coronary syndromes. METHODS AND RESULTS: Twenty-one
      consecutive patients with acute myocardial infarction (AMI), 14 patients with
      unstable angina, 11 patients with stable angina, and 20 control subjects were
      studied. The levels of vascular EC-SOD expression were assessed by the difference
      in plasma EC-SOD concentrations before and after intravenous heparan injection.
      In the patients with AMI, vascular EC-SOD expression (ng/mL) was significantly
      higher on day 1 after the onset of AMI (148+/-10) as compared with the control
      subjects (116+/-6, P<0.05). The vascular EC-SOD expression returned to the normal
      range on day 7 (104+/-8), and that level persisted thereafter. The vascular EC
      SOD expression was also significantly higher in the patients with unstable angina
      (160+/-13) than in those with stable angina (122+/-10) or in the controls (116+/
      6) (P<0.05 each). Moreover, in the patients with AMI, higher levels of vascular
      EC-SOD expression on day 1 were significantly associated with smaller myocardial
      infarct size (P<0.05). CONCLUSIONS: This is the first clinical demonstration
      showing that vascular EC-SOD may be upregulated in acute coronary syndromes in
      humans in vivo. EC-SOD may play an important protective role against increased
      oxidative stress during acute ischemic coronary events.

PMID- 14592845
TI  - Formation and metabolism of prebeta-migrating, lipid-poor apolipoprotein A-I.
AB  - The preferred extracellular acceptor of cell phospholipids and unesterified
      cholesterol in the process mediated by the ATP-binding cassette A1 (ABCA1)
      transporter is a monomolecular, prebeta-migrating, lipid-poor or lipid-free form
      of apolipoprotein (apo) A-I. This monomolecular form of apoA-I is quite distinct
      from the prebeta-migrating, discoidal high-density lipoprotein (HDL) that
      contains two or three molecules of apoA-I per particle and which are present as
      minor components of the HDL fraction in human plasma. The mechanism of the ABCA1
      mediated efflux of phospholipid and cholesterol from cells has been studied
      extensively. In contrast, much less attention has been given to the origin and
      subsequent metabolism of the acceptor lipid-free/lipid-poor apoA-I. There is a
      substantial body of evidence from studies conducted in vitro that a
      monomolecular, lipid-free/lipid-poor form of apoA-I dissociates from HDL during
      the remodeling of HDLs by plasma factors such as cholesteryl ester transfer
      protein, hepatic lipase, and phospholipid transfer protein. The rate at which
      apoA-I dissociates from HDL is influenced by the phospholipid composition of the
      particles and by the presence of apoA-II. This review describes current knowledge
      regarding the formation, metabolism, and regulation of monomolecular, lipid
      free/lipid-poor apoA-I in plasma.

PMID- 14592846
TI  - Vitamin E supplementation in patients with carotid atherosclerosis: reversal of
      altered oxidative stress status in plasma but not in plaque.
AB  - OBJECTIVE: Oxidative stress is believed to play a pivotal role in the initiation
      and progression of atherosclerosis. We analyzed whether vitamin E supplementation
      influences oxidative stress in plasma and atherosclerotic plaques of patients
      with severe atherosclerosis. METHODS AND RESULTS: In 16 patients who were
      candidates for carotid endarterectomy and in 32 age- and sex-matched controls,
      plasma levels of 7beta-hydroxycholesterol, 7-ketocholesterol, cholesterol, and
      vitamin E were measured. Patients were randomly allocated to standard treatment
      with or without 900 mg/d vitamin E. After 6 weeks of treatment, the reported
      variables were measured in plasma and plaques. The plasma vitamin E/cholesterol
      ratio was significantly lower in patients than in controls (3.05+/-0.6 versus
      6.3+/-1.7 micromol/mmol cholesterol, P<0.001). Plasma 7beta-hydroxycholesterol
      was significantly higher in patients than in controls (5.0+/-1.04 versus 4.4+/
      0.6 ng/mL, P<0.05). Patients who were given vitamin E supplementation showed a
      significant increase of plasma vitamin E with concomitant decrease of 7beta
      hydroxycholesterol. Conversely, no treatment dependence was observed in oxysterol
      or vitamin E content of plaques. CONCLUSIONS: An imbalance between oxidative
      stress and antioxidant status is present in patients with advanced
      atherosclerosis. Vitamin E supplementation improves this imbalance in plasma but
      not in plaques.

PMID- 14592847
TI  - Quantitative trait loci analysis for plasma HDL-cholesterol concentrations and
      atherosclerosis susceptibility between inbred mouse strains C57BL/6J and
      129S1/SvImJ.
AB  - OBJECTIVE: The C57BL/6 (B6) and 129 mouse inbred strains differ markedly in
      plasma HDL-cholesterol concentrations and atherosclerosis susceptibility after a
      high-fat diet consumption. To identify loci controlling these traits, we
      performed quantitative trait loci (QTL) analysis. METHODS AND RESULTS: We fed a
      high-fat diet to 294 (B6x129S1/SvImJ)F2 females for 14 weeks, measured plasma HDL
      concentrations and size of aortic fatty-streak lesions, genotyped F2 females, and
      performed QTL analysis. HDL concentrations were affected by six loci: Hdlq14 and
      Hdlq15 on chromosome 1 (peaks cM 80 and cM 104, logarithm of odds [LOD] 5.3 and
      9.7, respectively); Hdlq16 on chromosome 8 (cM 44, LOD 2.6); Hdlq17 on chromosome
      9 (cM 24, LOD 2.9); Hdlq18 on chromosome 12 (cM 20, LOD 5.9); and Hdlq19 on
      chromosome 2 (cM 90), which interacted with Hdlq15. Atherosclerosis
      susceptibility was affected by five loci: Ath17 on chromosome 10 (cM 34, LOD
      6.6); Ath18 on chromosome 12 (cM 16, LOD 3.7); Ath19 (chromosome 11, cM 60),
      which interacted with Ath18; and Ath20 (chromosome 10, cM 10), which interacted
      with Ath21 (chromosome 12, cM 50). CONCLUSIONS: We identified six loci for HDL
      and five loci for atherosclerosis susceptibility in a (B6x129S1/SvImJ)F2
      intercross.

PMID- 14592848
TI  - C-reactive protein stimulates MMP-1 expression in U937 histiocytes through
      Fc[gamma]RII and extracellular signal-regulated kinase pathway:: an implication
      of CRP involvement in plaque destabilization.
AB  - OBJECTIVE: It has been shown that plasma level of C-reactive protein (CRP) is an
      independent predictor for acute coronary syndromes and is associated with plaque
      weakening. However, the underlying mechanisms are not well understood. In this
      study, we investigated the effect of CRP on the expression of matrix
      metalloproteinase-1 (MMP-1) that has been implicated in plaque vulnerability by
      human U937 histiocytes and monocyte-derived macrophages. METHODS AND RESULTS:
      Enzyme-linked immunosorbent assay of MMP-1 in conditioned medium showed that
      treatment of U937 cells with 100 microg/mL of CRP for 24 hour led to a 3- to 5
      fold increase in MMP-1 secretion. CRP also markedly stimulated MMP-1 release from
      human monocyte-derived macrophages. In contrast, CRP had no effect on tissue
      inhibitor of metalloproteinase-1 (TIMP-1) secretion. Northern blot showed that
      CRP upregulated MMP-1 mRNA expression. Collagenase activity assay showed that CRP
      increased collagen-degrading activity in cell-conditioned medium. Furthermore,
      results showed that the stimulation of MMP-1 secretion by CRP was inhibited by
      anti-CD32, but not by anti-CD64 antibody, and by mitogen-activated protein
      kinase/extracellular signal-regulated kinase (MEK) inhibitor PD98059. Finally,
      Western blot showed that CRP stimulated phosphorylation of extracellular signal
      regulated kinase. CONCLUSIONS: This study demonstrates that CRP stimulates MMP-1
      expression by U937 cells through FcgammaRII and extracellular signal-regulated
      kinase pathway. These findings suggest that CRP may promote matrix degradation
      and thus contribute to plaque vulnerability.

PMID- 14592849
TI  - Evidence for a proinflammatory and proteolytic environment in plaques from
      endarterectomy segments of human carotid arteries.
AB  - OBJECTIVES: Based on previous observations on apolipoprotein(a), apo(a), in human
      unstable carotid plaques, we explored whether in the inflammatory environment of
      human atheroma, proteolytic events affect other hepatic and topically generated
      proteins in relation to the issue of plaque stability. METHODS AND RESULTS: Forty
      unstable and 24 stable plaques from endarterectomy segments of affected human
      carotid arteries were extracted with buffered saline (PBS) and then 6 mol/L
      guanidine-hydrochloride (GdHCl) to identify loosely and tightly bound products,
      respectively. The extracts were studied before and after ultracentrifugation at d
      1.21 g/mL. In the extracts, the concentrations of interleukin (IL)-6, -8, and -18
      were significantly higher in the unstable plaques and correlated to those of MMP
      2 and MMP-9. By Western blots, both apoB and apo(a) were highly fragmented and
      mostly present in the d 1.21 bottom that also contained fragments of apoE (10 and
      22 kDa), decorin, biglycan, and versican. Fragmentation was higher in the
      unstable plaques. In baseline plasmas, concentrations of lipids, lipoproteins,
      and ILs did not differ between patients with unstable and stable plaques.
      CONCLUSIONS: In unstable and to a lesser extent in stable plaques, there is a
      proinflammatory and proteolytic microenvironment with the generation of fragments
      with potential pathobiological significance that requires investigation.

PMID- 14592850
TI  - The role of [beta]-transducin repeat-containing protein ([beta]-TrCP) in the
      regulation of NF-[kappa]B in vascular smooth muscle cells.
AB  - OBJECTIVE: Degradation of IkappaB is an essential step in nuclear factor (NF)
      kappaB activation. However, the determinants regulating this process have not
      been defined in vascular smooth muscle cells (VSMCs). We hypothesized that the E3
      ligase, beta-transducin repeat-containing protein 1 (beta-TrCP1), was a rate
      determining mediator that regulates the ubiquitin-mediated degradation of
      IkappaBalpha (in VSMC). METHODS AND RESULTS: Upregulation of beta-TrCP1
      accelerated the rate of IkappaBalpha degradation, leading to increased NF-kappaB
      activity. In contrast, VSMCs harboring a dominant-negative beta-TrCP1 transgene
      lacking the F-box domain exhibited a reduction in serum-stimulated NF-kB activity
      but no alteration in response to tumor necrosis factor (TNF). These findings
      suggest that beta-TrCP1 increases the rate of NF-kappaB activation but is not
      rate-limiting in response to TNF in VSMCs. Endogenous beta-TrCP1 expression was
      regulated through the conserved Wnt cascade. Upregulation of Wnt1 resulted in
      beta-catenin-mediated activation of Tcf-4, leading to increased beta-TrCP1
      expression and NF-kappaB activity. Furthermore, VSMCs harboring a Tcf-4 mutant
      lacking a beta-catenin binding domain exhibited a significant reduction in beta
      TrCP1 expression along with abolishment of NF-kappaB activity. CONCLUSIONS: We
      provide the first evidence of crosstalk between the Wnt cascade and NF-kappaB
      signaling in VSMCs. This crosstalk is mediated through the E3-ligase, beta-TrCP1.

PMID- 14592851
TI  - Decreased macrophage paraoxonase 2 expression in patients with
      hypercholesterolemia is the result of their increased cellular cholesterol
      content: effect of atorvastatin therapy.
AB  - OBJECTIVE: To analyze paraoxonase2 (PON2) expression in human monocyte-derived
      macrophages (HMDM) from patients with hypercholesterolemia in relation to
      cellular cholesterol and oxidative stress. METHODS AND RESULTS: Ten healthy
      subjects (controls) and 10 patients with hypercholesterolema who received 20-mg/d
      atorvastatin participated in the study. The patients' versus controls' HMDM
      demonstrated increased cholesterol content (270%) and oxidative stress (30% to
      45%). Atorvastatin therapy reduced these parameters (59% and 25%, respectively).
      The patients' versus controls' macrophage-PON2 mRNA expression and PON2 activity
      were lower (100% and 40%, respectively), and atorvastatin therapy increased these
      parameters (76% and 200%, respectively). Untreated patient HMDM incubation with
      atorvastatin (0 to 10 micromol/L) resulted in a dose-dependent reduction in
      cellular cholesterol content and in cell-mediated low-density lipoprotein (LDL)
      oxidation up to 79% and 66%, respectively. In parallel, PON2 mRNA expression and
      PON2 activity increased dose-dependently up to 3.6- and 2.1-fold, respectively.
      On incubation of control HMDM with acetylated-LDL or aggregated-LDL, cellular
      cholesterol content increased (77% and 100%), and macrophage-PON2 activity
      decreased (49% and 22%), respectively. In contrast, oxidized LDL increased both
      cellular oxidative stress and PON2 expression. CONCLUSIONS: HMDM-PON2 expression
      is reduced in patients with hypercholesterolemia as a result of their increased
      cellular cholesterol content. Atorvastatin therapy reduced both macrophage
      oxidative stress and cholesterol content, and upregulated PON2 expression, thus
      contributing to attenuation of foam cells formation.

PMID- 14592853
TI  - Nicotine enhances angiotensin II-induced mitogenic response in vascular smooth
      muscle cells and fibroblasts.
AB  - OBJECTIVE: The pathogenetic mechanism of tobacco-related cardiovascular diseases
      is still not well defined. We examined the potential possibility of an
      interaction between nicotine, a major component of cigarette smoke, and
      angiotensin II (Ang II), which plays an important role in the pathogenesis of
      cardiovascular diseases characterized by Ang II type 1 (AT1) receptor-mediated
      abnormal growth of vascular smooth muscle cells (VSMC) and fibroblasts. METHODS
      AND RESULTS: Nicotine or Ang II-stimulated [3H]thymidine incorporation and c-fos
      expression in adult rat aortic VSMC and adventitial fibroblast. The nicotine
      induced DNA synthesis was not affected by valsartan, an AT1 receptor-specific
      blocker, or PD123319, an Ang II type 2 (AT2) receptor-specific antagonist.
      Nicotine or Ang II stimulation rapidly increased extracellular signal-regulated
      kinase (ERK) activation, tyrosine- and serine-phosphorylation of signal
      transducer and activator of transcription (STAT)1 and STAT3, and p38 mitogen
      activated protein kinase (p38 MAPK), in both cell types. Interestingly, co
      administration of nicotine and Ang II at lower doses, which did not affect cell
      growth, induced DNA synthesis and c-fos expression accompanied by enhancement of
      ERK, STAT, and p38MAPK activity. PD98059, a mitogen-activated protein kinase/ERK
      kinase inhibitor, or SB23058, a p38MAPK inhibitor, significantly attenuated the
      vasotrophic effect of nicotine and Ang II. CONCLUSIONS: These results suggest
      that nicotine exerts a growth-promoting effect on vascular cells and enhances the
      Ang II-induced vasotrophic effect, which is at least partly mediated by the
      activation of ERK, STAT, and p38MAPK.

PMID- 14592852
TI  - Evidence for protein kinase C-mediated activation of Rho-kinase in a porcine
      model of coronary artery spasm.
AB  - OBJECTIVE: We have recently demonstrated that protein kinase C (PKC) and Rho
      kinase play important roles in coronary vasospasm in a porcine model. However, it
      remains to be examined whether there is an interaction between the two molecules
      to cause the spasm. METHODS AND RESULTS: A segment of left porcine coronary
      artery was chronically treated with IL-1beta-bound microbeads in vivo. Two weeks
      after the operation, phorbol ester caused coronary spasm in vivo and coronary
      hypercontractions in vitro at the IL-1beta-treated segment; both were
      significantly inhibited by hydroxyfasudil, a specific Rho-kinase inhibitor.
      Guanosine 5'-[gamma-thio]triphosphate (GTPgammaS), which activates Rho with a
      resultant activation of Rho-kinase, enhanced Ca2+ sensitization of permeabilized
      vascular smooth muscle cells, which were resistant to the blockade of PKC by
      calphostin C. The GTPgammaS-induced Ca2+ sensitization was greater in the spastic
      segment than in the control segment. Western blot analysis revealed that only
      PKCdelta isoform was activated during the hypercontraction. CONCLUSIONS: These
      results demonstrate that PKC and Rho-kinase coexist on the same intracellular
      signaling pathway, with PKC located upstream on Rho-kinase, and that among the
      PKC isoforms, only PKCdelta may be involved. Thus, the strategy to inhibit Rho
      kinase rather than PKC may be a more specific and useful treatment for coronary
      spasm.

PMID- 14592854
TI  - Cyclooxygenase-2 expression and inhibition in atherothrombosis.
AB  - Arachidonic acid metabolism plays an important role in acute ischemic syndromes
      affecting the coronary or cerebrovascular territory, as reflected by biochemical
      measurements of eicosanoid biosynthesis and the results of inhibitor trials in
      these settings. Two cyclooxygenase (COX)-isozymes have been characterized, COX-1
      and COX-2, that differ in terms of regulatory mechanisms of expression, tissue
      distribution, substrate specificity, preferential coupling to upstream and
      downstream enzymes, and susceptibility to inhibition by the extremely
      heterogeneous class of COX-inhibitors. Although the role of platelet COX-1 in
      acute coronary syndromes and ischemic stroke is firmly established through
      approximately 20 years of thromboxane metabolite measurements and aspirin trials,
      the role of COX-2 expression and inhibition in atherothrombosis is substantially
      uncertain, because the enzyme was first characterized in 1991 and selective COX-2
      inhibitors became commercially available only in 1998. In this review, we discuss
      the pattern of expression of COX-2 in the cellular players of atherothrombosis,
      its role as a determinant of plaque "vulnerability," and the clinical
      consequences of COX-2 inhibition. Recent studies from our group suggest that
      variable expression of upstream and downstream enzymes in the prostanoid
      biosynthetic cascade may represent important determinants of the functional
      consequences of COX-2 expression and inhibition in different clinical settings.

PMID- 14592856
TI  - Introduction. Biochemical basis for disease of the neuromuscular junction.

PMID- 14592855
TI  - Decoding transcriptional programs regulated by PPARs and LXRs in the macrophage:
      effects on lipid homeostasis, inflammation, and atherosclerosis.
AB  - Macrophages play essential roles in immunity and homeostasis. As professional
      scavengers, macrophages phagocytose microbes and apoptotic and necrotic cells and
      take up modified lipoprotein particles. These functions require tightly regulated
      mechanisms for the processing and disposal of cellular lipids. Under pathological
      conditions, arterial wall macrophages become foam cells by accumulating large
      amounts of cholesterol, contributing to the development of atherosclerosis.
      Peroxisome proliferator-activated receptors (PPARs) and liver X receptors (LXRs)
      are members of the nuclear receptor superfamily of transcription factors that
      have emerged as key regulators of macrophage homeostasis. PPARs and LXRs control
      transcriptional programs involved in processes of lipid uptake and efflux,
      lipogenesis, and lipoprotein metabolism. In addition, PPARs and LXRs negatively
      regulate transcriptional programs involved in the development of inflammatory
      responses. This review summarizes recent efforts to decode the differential and
      overlapping roles of PPARs and LXRs in the context of macrophage lipid
      homeostasis and the control of inflammation.

PMID- 14592857
TI  - Neurophysiology of the neuromuscular junction: overview.
AB  - This manuscript reviews the physiology of neuromuscular transmission with
      emphasis on four features: (1) the structure of the neuromuscular junction, (2)
      release of vesicles of acetylcholine from the nerve terminal, (3) the roles of
      postsynaptic Na(+) channels and acetylcholine receptors in converting the
      chemical signal from the nerve terminal into a propagated action potential on the
      muscle fiber, and (4) the safety factor for neuromuscular transmission. It also
      introduces new information about how the neuromuscular junction maintains
      physiological integrity during muscle fiber stretch and contraction.

PMID- 14592858
TI  - Ca2+ channels and synaptic transmission at the adult, neonatal, and P/Q-type
      deficient neuromuscular junction.
AB  - Different types of voltage-activated Ca(2+) channels have been established based
      on their molecular structure and pharmacological and biophysical properties. One
      of them, the P/Q-type, is the main channel involved in nerve-evoked
      neurotransmitter release at neuromuscular junctions and the immunological target
      in Eaton-Lambert Syndrome. At adult neuromuscular junctions, L- and N-type Ca(2+)
      channels become involved in transmitter release only under certain experimental
      or pathological conditions. In contrast, at neonatal rat neuromuscular junctions,
      nerve-evoked synaptic transmission depends jointly on both N- and P/Q-type
      channels. Synaptic transmission at neuromuscular junctions of the ataxic P/Q-type
      Ca(2+) channel knockout mice is also dependent on two different types of
      channels, N- and R-type. At both neonatal and P/Q knockout junctions, the K(+)
      evoked increase in miniature endplate potential frequency was not affected by N
      type channel blockers, but strongly reduced by both P/Q- and R-type channel
      blockers. These differences could be accounted for by a differential location of
      the channels at the release site, being either P/Q- or R-type Ca(2+) channels
      located closer to the release site than N-type Ca(2+) channels. Thus, Ca(2+)
      channels may be recruited to mediate neurotransmitter release where P/Q-type
      channels seem to be the most suited type of Ca(2+) channel to mediate exocytosis
      at neuromuscular junctions.

PMID- 14592859
TI  - Effect of inherited abnormalities of calcium regulation on human neuromuscular
      transmission.
AB  - Synaptotagmins are abundant synaptic proteins that represent the best candidate
      for the calcium sensor at the nerve terminal. The pore-forming, voltage-sensing
      transmembrane alpha-1 subunit of the P/Q voltage-gated calcium channel (or
      Ca(v)2.1) encoded by the CACNA1A gene is another major component of the process
      of action potential-evoked exocytosis at the adult mammalian neuromuscular
      junction. Defects of these proteins, in nonhuman species, result in severe
      disruption of rapid synaptic transmission. This paper investigates the molecular
      bases of inherited presynaptic deficits of neuromuscular transmission in humans.
      Patients with congenital presynaptic failure, including two patients with
      episodic ataxia type 2 (EA-2) due to CACNA1A mutations, were studied with muscle
      biopsy, microelectrode studies, electron microscopy, DNA amplification, and
      sequencing. All patients, including EA-2 patients, showed selective failure of
      the action potential-dependent release without reduction of the spontaneous
      release of neurotransmitter. In addition, patients with EA-2 showed partial
      blockade of neuromuscular transmission with the N-type blocker omega-conotoxin
      not seen in controls. The EM showed a varied degree of increased complexity of
      postsynaptic folds. Mutational analysis in candidate genes, including human
      synaptotagmin II, syntaxin 1A, synaptobrevin I, SNAP 25, CACNA1A, CACNB2, and
      Rab3A, was unrevealing. Although no mutations in candidate genes were found in
      patients with inborn presynaptic failure, functional and structural similarities
      between this group and patients with EA-2 due to CACNA1A mutations suggest a
      common pathogenic mechanism.

PMID- 14592860
TI  - Transmitter release deficits at the neuromuscular synapse of mice with mutations
      in the Cav2.1 (alpha1A) subunit of the P/Q-type Ca2+ channel.

PMID- 14592861
TI  - Protein ubiquitylation and synaptic function.
AB  - Conjugation of ubiquitin to proteins is a well-established signal to regulate an
      ever expanding range of cellular processes. Here, we discuss recent findings that
      deeply link ubiquitin signaling to synaptic activity.

PMID- 14592862
TI  - Nicotinic acetylcholine receptors of muscles and nerves: comparison of their
      structures, functional roles, and vulnerability to pathology.
AB  - There are fetal and adult subtypes of muscle nicotinic receptors (AChRs), whose
      structures and functional roles are reasonably well known. Mutations of their
      subunits cause congenital myasthenic syndromes. An autoimmune response to them
      causes myasthenia gravis (MG). The main immunogenic region (MIR) on muscle AChRs
      accounts for many aspects of the pathological mechanisms by which the autoimmune
      response impairs neuromuscular transmission. There are many other AChR subtypes,
      each defined by a different combination of subunits, some of which are
      transiently expressed in muscle during development, others of which are expressed
      in keratinocytes, vascular and bronchial epithelia, and other nonneuronal cells,
      as well as in a wide variety of neurons. Their varied structures and functional
      roles are much less well known. Mutations in subunits of some of these AChRs have
      thus far been associated with rare forms of epilepsy and dysautonomia, but other
      genetic diseases associated with them probably remain to be discovered.
      Autoimmune responses to some of these subunits are associated with rare
      dysautonomias and a skin disease. The pathological mechanisms by which these
      autoimmune responses impair function are much less well known than in the case of
      MG. AChRs may provide useful drug targets in several neurological diseases. By
      far, the biggest direct medical impact of AChRs is addiction to tobacco, which is
      mediated by nicotine acting on a variety of neuronal AChRs.

PMID- 14592863
TI  - Synapse-specific gene expression at the neuromuscular junction.
AB  - Agrin is the key neural factor that controls muscle postsynaptic differentiation,
      including the induction of synapse-specific transcription via neuregulins. In
      1995, the promoter element responsible for the targeting of AChR delta and
      epsilon gene transcription to the skeletal muscle subsynaptic area was
      identified. This element, named N-box, recruits the Ets-related transcription
      factor GABP to AChR delta and epsilon promoters, and both the N-box and GABP are
      required to obtain transcriptional stimulation by neuregulins. The physiological
      importance of the N-box has been definitively established with the discovery of
      myasthenic families carrying single-point mutations in the N-box of the AChR
      epsilon gene promoter and showing reduced levels of AChR epsilon subunit
      expression. The control of synapse-specific transcription by agrin and
      neuregulins through the N-box and GABP is not restricted to the case of AChR
      genes. The same regulation holds true for the ACh esterase and utrophin genes,
      thus showing that nerve-induced transcriptional activation of several synapse
      specific genes is triggered by a common mechanism involving agrin, neuregulins,
      and ultimately the N-box and Ets-related transcription factors.

PMID- 14592864
TI  - Regulation of nicotinic acetylcholine receptor assembly.
AB  - The four muscle-type nicotinic acetylcholine receptor (AChR) subunits, alpha,
      beta, gamma, and delta, assemble into functional alpha(2)betagammadelta pentamers
      in the endoplasmic reticulum (ER) through a series of interdependent folding and
      oligomerization events. The first stable assembly intermediate is a trimer
      composed of alpha, beta, and gamma subunits. The formation of alphabetagamma
      trimers initiates a series of subunit folding and processing events that allow
      addition of delta subunits to form alphabetagammadelta tetramers. Subunit folding
      and processing continue with formation of the ligand-binding sites on the alpha
      subunit of alphabetagammadelta tetramers and the second alpha subunit added to
      assemble alpha(2)betagammadelta pentamers. AChR assembly is inefficient. Only 20
      30% of synthesized subunits assemble into mature receptors in the ER, while the
      remaining unassembled subunits are degraded. However, the efficiency of subunit
      assembly can be regulated under certain conditions leading to higher AChR
      expression. Increased intracellular cAMP levels cause a 2- to 3-fold increase in
      AChR assembly efficiency and a comparable increase in surface expression.
      Additionally, block of ubiquitin-proteasome degradation appears to enhance AChR
      assembly and expression. Thus, the regulation of AChR assembly through
      posttranslational mechanisms is a potential therapeutic target for increasing
      AChR expression in diseases in which expression is compromised.

PMID- 14592865
TI  - Structure and function of AChBP, homologue of the ligand-binding domain of the
      nicotinic acetylcholine receptor.
AB  - Acetylcholine-binding protein (AChBP) is a novel protein with high similarity to
      the extracellular domain of the nicotinic acetylcholine receptor. AChBP lacks the
      transmembrane domains and intracellular loops typical for the nAChRs. AChBP is
      secreted from glia cells in the central nervous system of the freshwater snail,
      Lymnaea stagnalis, where it modulates synaptic transmission. AChBP forms
      homopentamers with pharmacology that resembles the alpha(7)-type of nicotinic
      receptors. As such, AChBP is a good model for the ligand-binding domain of the
      nAChRs. In the crystal structure of AChBP at 2.7 A, each protomer has a modified
      immunoglobulin fold. Almost all residues previously shown to be involved in
      ligand binding in the nicotinic receptor are found in a pocket at the subunit
      interface, which is lined with aromatic residues. The AChBP crystal structure
      explains many of the biochemical studies on the nicotinic acetylcholine
      receptors. Surprisingly, the interface between protomers is relatively weakly
      conserved between families in the superfamily of pentameric ligand-gated ion
      channels. The lack of conservation has implications for the mechanism of gating
      of the ion channels.

PMID- 14592866
TI  - The binding site of acetylcholine receptor: from synthetic peptides to solution
      and crystal structure.
AB  - Our group has been employing short synthetic peptides, encompassing sequences
      from the acetylcholine receptor (AChR) alpha-subunit for the analysis of the
      binding site of the AChR. A 13-mer peptide mimotope, with similar structural
      motifs to the AChR binding region, was selected by alpha-bungarotoxin (alpha-BTX)
      from a phage-display peptide library. The solution structure of a complex between
      this library-lead peptide and alpha-BTX was solved by NMR spectroscopy. On the
      basis of this NMR study and on structure-function analysis of the AChR binding
      site, and in order to obtain peptides with higher affinity to alpha-BTX,
      additional peptides resulting from systematic residue replacement in the lead
      peptide were designed and characterized. Of these, four peptides, designated high
      affinity peptides (HAPs), homologous to the binding region of the AChR, inhibited
      the binding of alpha-BTX to the AChR with an IC(50) of 2 nM. The solution and
      crystal structures of complexes of alpha-BTX with HAP were solved, demonstrating
      that the HAP fits snugly to alpha-BTX and adopts a beta-hairpin conformation. The
      X-ray structures of the bound HAP and the homologous loop of the acetylcholine
      binding protein (AChBP) are remarkably similar. Their superposition results in a
      model indicating that alpha-BTX wraps around the receptor binding-site loop and,
      in addition, binds tightly at the interface of two of the receptor subunits,
      where it inserts a finger into the ligand-binding site. Our proposed model
      explains the strong antagonistic activity of alpha-BTX and accommodates much of
      the biochemical data on the mode of interaction of alpha-BTX with the AChR.

PMID- 14592867
TI  - Agonist-induced transitions of the acetylcholine receptor.
AB  - Anti-acetylcholine receptor (AChR) monoclonal antibody 383C binds to the beta
      hairpin loop alpha(187-199) of only one of the two Torpedo AChR alpha subunits.
      The loop recognized is associated with the alpha subunit corresponding to the
      high-affinity d-tubocurarine (dTC) binding site. Desensitization of the receptor
      with carbamylcholine completely blocks the binding of 383C. Mild reduction of
      AChR alpha subunit cys 192-193 disulfide with DTT and subsequent reaction with 5
      iodoacetamidofluorescein label only the high-affinity dTC alpha subunit.
      Rhodamine-labeled alpha-bungarotoxin (R-Btx) binds to the unlabeled AChR alpha
      subunit as monitored by fluorescence resonance energy transfer between the
      fluorescein and rhodamine dyes. A 10-A contraction of the distance between the
      dyes is observed following the addition of carbamylcholine. In a small angle X
      ray diffraction experiment exploiting anomalous X-ray scattering from Tb(III)
      ions titrated into AChR Ca(II) binding sites, we find evidence for a change in
      the Tb(III) ion distribution in the region of the ion channel following addition
      of carbamylcholine to the AChR. The carbamylcholine-induced loss of the 383C
      epitope, the 10-A contraction of the beta-hairpin loop, and the loss of
      multivalent cations from the channel likely represent the first molecular
      transitions leading to AChR channel opening.

PMID- 14592868
TI  - Structural abnormalities of the AChR caused by mutations underlying congenital
      myasthenic syndromes.
AB  - The objective was to define the molecular mechanisms underlying congenital
      myasthenic syndromes (CMS) by studying mutations within genes encoding the
      acetylcholine receptor (AChR) and related proteins at the neuromuscular junction.
      It was found that mutations within muscle AChRs are the most common cause of CMS.
      The majority are located within the epsilon-subunit gene and result in AChR
      deficiency.

PMID- 14592869
TI  - Congenital myasthenic syndrome in cattle due to homozygosity for a truncating
      mutation in the acetylcholine receptor (AChR) epsilon-subunit gene.

PMID- 14592870
TI  - Mechanistic diversity underlying fast channel congenital myasthenic syndromes.
AB  - A host of missense mutations in muscle nicotinic receptor subunits have been
      identified as the cause of congenital myasthenic syndromes (CMS). Two classes of
      CMS phenotypes have been identified: slow channel myasthenic syndromes (SCCMSs)
      and fast channel myasthenic syndromes (FCCMSs). Although both have similar
      phenotypic consequences, they are physiologic opposites. Expression of the FCCMS
      phenotype requires the missense mutation to be accompanied by a second mutation,
      either a null or a missense mutation, in the second allele encoding the same
      receptor subunit. This seemingly rare scenario has arisen with surprisingly high
      incidence over the past few years, and analyses of the syndromes have revealed a
      diverse array of mechanisms underlying the pathology. This review focuses on new
      mechanisms underlying the FCCMS.

PMID- 14592871
TI  - Congenital myasthenic syndromes: multiple molecular targets at the neuromuscular
      junction.
AB  - Congenital myasthenic syndromes (CMS) stem from defects in presynaptic, synaptic,
      and postsynaptic proteins. The presynaptic CMS are associated with defects that
      curtail the evoked release of acetylcholine (ACh) quanta or ACh resynthesis.
      Defects in ACh resynthesis have now been traced to mutations in choline
      acetyltransferase. A synaptic CMS is caused by mutations in the collagenic tail
      subunit (ColQ) of the endplate species of acetylcholinesterase that prevent the
      tail subunit from associating with catalytic subunits or from becoming inserted
      into the synaptic basal lamina. Most postsynaptic CMS are caused by mutations in
      subunits of the acetylcholine receptor (AChR) that alter the kinetic properties
      or decrease the expression of AChR. The kinetic mutations increase or decrease
      the synaptic response to ACh and result in slow- and fast-channel syndromes,
      respectively. Most low-expressor mutations reside in the AChR epsilon subunit and
      are partially compensated by residual expression of the fetal-type gamma subunit.
      In a subset of CMS patients, endplate AChR deficiency is caused by mutations in
      rapsyn, a molecule that plays a critical role in concentrating AChR in the
      postsynaptic membrane.

PMID- 14592872
TI  - Autoimmune diseases as the loss of active "self-control".
AB  - Converging experimental evidence indicates that the clinical expression of
      autoimmunity is under the control of T cell-mediated immunoregulatory circuits.
      Several types of suppressor T cells have been described. Some of them are closely
      dependent upon cytokines such as TH2 cells and Tr1 cells. Others appear to rely
      more on cell-cell contact (such as CD25+ CD62L+ T cells), although some
      cytokines, notably TGF-beta, may be involved in their growth or their mode of
      action. It is tempting to separate suppressor cells that appear spontaneously,
      such as CD25+ T cells and NKT cells (innate immunoregulation), from those that
      are only observed after antigen administration, such as TH2 cells and Tr1 cells
      (adaptive immunoregulation). The role of these diverse cell types in the control
      of the onset or the progression of autoimmune diseases is likely, but still a
      matter of debate. A central question is to determine whether immune dysregulation
      precedes the burst of pathogenic autoimmunity.

PMID- 14592873
TI  - Immunology of paraneoplastic syndromes: overview.
AB  - Cancers that cause disturbances of organs or tissues remote from the site of the
      tumor or its metastases are called paraneoplastic syndromes. The nervous system
      can be affected at virtually any site, including the neuromuscular junction
      (e.g., Lambert-Eaton myasthenic syndrome, myasthenia gravis). Paraneoplastic
      syndromes affecting the central nervous system are characterized by (1) high
      titers of antibodies that react with both the cancer and the affected portion of
      the nervous system, (2) specifically reacting T cells in the blood and
      cerebrospinal fluid, and (3) autopsy evidence of neuronal destruction,
      inflammatory infiltrates, and antibody penetration. Clinically, paraneoplastic
      syndromes affecting the central nervous system are usually subacute in onset,
      rapid in evolution, and cause severe damage, but generally stabilize after
      several months with or without treatment. Immune suppression does not appear to
      be particularly effective in treating these disorders. Treatment of the
      underlying cancer sometimes ameliorates symptoms.

PMID- 14592874
TI  - Pathogenic autoantibodies in the lambert-eaton myasthenic syndrome.
AB  - Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disorder of
      neuromuscular transmission in which antibodies are directed against voltage-gated
      calcium channels (VGCCs). We studied the action of LEMS immunoglobulin G (IgG) on
      cloned human VGCCs stably transfected into human embryonic kidney cells (HEK293).
      All LEMS IgGs tested bound to the surface of the P/Q-type VGCC cell line and
      caused a significant reduction in whole-cell calcium currents in these cells. By
      contrast, only 2 out of 6 IgGs bound extracellularly to the N-type VGCC cell
      line, and none of the LEMS IgGs tested was able to reduce whole-cell calcium
      currents in these cells. We used this apparent specificity of LEMS IgG for the
      P/Q-type VGCC to investigate the action of these IgGs on model systems where a
      number of different VGCC populations exist in equilibrium. LEMS IgG caused a
      significant downregulation in the omega-agatoxin IVA-sensitive P/Q-type VGCCs of
      cultured rat cerebellar neurons, but this was accompanied by a concomitant rise
      in the "resistant" R-type VGCCs. By using the passive transfer model of LEMS,
      similar results were observed at the mouse neuromuscular junction, where a
      significant reduction in P/Q-type VGCCs was paralleled by an increase in L- and R
      type VGCCs. These results demonstrate an unexpected plasticity in the expression
      of VGCCs in mammalian neurons and may represent a mechanism by which the
      pathogenic effects of LEMS IgG are reduced.

PMID- 14592875
TI  - LEMS IgG binds to extracellular determinants on N-type voltage-gated calcium
      channels, but does not reduce VGCC expression.

PMID- 14592876
TI  - HLA-B8 in patients with the Lambert-Eaton myasthenic syndrome reduces likelihood
      of associated small cell lung carcinoma.

PMID- 14592877
TI  - Autoimmune disorders of neuronal potassium channels.
AB  - Antibodies to voltage-gated potassium channels (VGKCs) appear likely to be the
      effector mechanisms in many patients with acquired peripheral nerve
      hyperexcitability (APNH) syndromes, a group of disorders that include
      neuromyotonia, cramp-fasciculation syndrome, and Isaacs' syndrome. They may
      contribute to the associated autonomic changes. Through a central action, they
      may also be the effector mechanism in those with Morvan's syndrome and in some
      patients with limbic encephalitis. Evidence supporting this hypothesis includes
      the increased association of APNH with autoimmune diseases (in particular,
      myasthenia gravis and thymoma), the response to plasmapheresis, passive transfer
      of APNH to experimental animals by patients' plasma or immunoglobulins, the
      action of their serum on VGKC currents studied in vitro, and the presence in many
      patients of IgG antibodies to VGKCs.

PMID- 14592878
TI  - Neuronal ganglionic acetylcholine receptor autoimmunity.
AB  - We have developed and validated an assay to detect serum antibodies specific for
      the ganglionic AChR. The assay uses ganglionic AChR solubilized from membranes of
      the human neuroblastoma cell line (IMR-32) as antigen. The ganglionic AChR is
      radiolabeled by complexing with 125I-epibatidine. Among patients with acquired
      dysautonomia, seropositivity is highly associated with the diagnosis of
      idiopathic or paraneoplastic autonomic neuropathy and can distinguish these
      disorders from other forms of autonomic dysfunction. Ganglionic AChR binding
      antibodies are detectable in 50% of patients with subacute autoimmune autonomic
      neuropathy (AAN). These patients often have a high antibody value (>0.2 nmol/L).
      Lower values (0.05-0.20 nmol/L) are found in approximately 10% of patients with
      limited AAN.

PMID- 14592879
TI  - Humoral and cellular autoimmune responses in stiff person syndrome.
AB  - Stiff person syndrome (SPS) is a chronic autoimmune disease associated with
      humoral and cellular immune responses to glutamic acid decarboxylase (GAD) 65.
      Another chronic autoimmune disease, type 1 diabetes (T1D), is also associated
      with autoimmune responses to this antigen, but T1D patients develop SPS only
      extremely rarely and only a third of SPS patients develop T1D (mostly mild
      manifestations in adulthood). In a previous study, we described important
      differences between T1D and SPS in the autoimmune response to GAD 65: (1) T cells
      of SPS patients recognize epitopes in the middle of GAD 65 (amino residues 81-171
      and 313-403), whereas patients with T1D preferentially recognize another middle
      (161-243) and a C-terminal region (473-555); and (2) GAD antibodies (Abs) were
      nearly exclusively of the Th1-associated IgG1 type in T1D, whereas SPS patients
      had both Th1- and Th2-associated IgG4 and IgE GAD Abs. These differences were not
      simply related to different HLA alleles. Fine epitope mapping revealed further
      distinct T cell epitopes in both diseases despite similar HLA background.
      Therefore, a single autoantigen can elicit different immune responses causing
      distinct chronic autoimmune diseases possibly related to a Th1 or Th2 bias of the
      disease.

PMID- 14592880
TI  - The role of thymomas in the development of myasthenia gravis.
AB  - Thymic pathology occurs in 80-90% of myasthenia gravis patients. Significant
      associations between different thymic alterations and clinical findings are
      discussed. To highlight peculiarities in thymoma-associated myasthenia gravis, we
      briefly review myasthenia gravis associated with thymic lymphofollicular
      hyperplasia (TFH) and thymic atrophy.

PMID- 14592881
TI  - Scenarios for autoimmunization of T and B cells in myasthenia gravis.
AB  - We have studied responses in thymoma patients to interferon-alpha and to the
      acetylcholine receptor (AChR) in early-onset myasthenia gravis (EOMG), seeking
      clues to autoimmunizing mechanisms. Our new evidence implicates a two-step
      process: (step 1) professional antigen-presenting cells and thymic epithelial
      cells prime AChR-specific T cells; then (step 2) thymic myoid cells subsequently
      provoke germinal center formation in EOMG. Our unifying hypothesis proposes that
      AChR epitopes expressed by neoplastic or hyperplastic thymic epithelial cells
      aberrantly prime helper T cells, whether generated locally or infiltrating from
      the circulation. These helper T cells then induce antibody responses against
      linear epitopes that cross-react with whole AChR and attack myoid cells in the
      EOMG thymus. The resulting antigen-antibody complexes and the recruitment of
      professional antigen-presenting cells increase the exposure of thymic cells to
      the infiltrates and provoke local germinal center formation and determinant
      spreading. Both these and the consequently enhanced heterogeneity and
      pathogenicity of the autoantibodies should be minimized by early thymectomy.

PMID- 14592882
TI  - A new model linking intrathymic acetylcholine receptor expression and the
      pathogenesis of myasthenia gravis.
AB  - The thymus is thought to play an important role in the pathogenesis of myasthenia
      gravis (MG), an autoimmune disease characterized by skeletal muscle weakness.
      However, its role remains a mystery. The studies described represent our efforts
      to determine how intrathymic expression of the neuromuscular type of
      acetylcholine receptors (nAChRs) is involved in the immunopathogenesis of MG. We
      review our work characterizing the expression of the alpha subunit of nAChR
      (nAChRalpha) in the thymus and advance a new hypothesis that examines the
      intrathymic expression of this autoantigen in disease pathogenesis.

PMID- 14592883
TI  - Human myoid cells protect thymocytes from apoptosis.

PMID- 14592884
TI  - Analysis of SjTREC levels in thymus from MG patients and normal children.

PMID- 14592885
TI  - Analysis of CD4+CD25+ cell population in the thymus from myasthenia gravis
      patients.
AB  - The present study is aimed at exploring the regulatory CD4(+)CD25(+) T cells in
      the thymus from myasthenia gravis (MG) patients. In early-onset MG, the thymus is
      hyperplastic and contains autoreactive activated T cells. Preliminary studies
      indicate that these CD4(+)CD25(+) cells include activated autoreactive T cells.
      Studies to characterize the phenotype and suppressive capacity of these cells
      will be discussed.

PMID- 14592886
TI  - Expression of transforming growth factor-beta1 in thymus of myasthenia gravis
      patients: correlation with pathological abnormalities.

PMID- 14592887
TI  - T cells and cytokines in the pathogenesis of acquired myasthenia gravis.
AB  - Although the symptoms of myasthenia gravis (MG) and experimental MG (EAMG) are
      caused by autoantibodies, CD4(+) T cells specific for the target antigen, the
      nicotinic acetylcholine receptor, and the cytokines they secrete, have an
      important role in these diseases. CD4(+) T cells have a pathogenic role, by
      permitting and facilitating the synthesis of high-affinity anti-AChR antibodies.
      Th1 CD4(+) cells are especially important because they drive the synthesis of
      anti-AChR complement-fixing IgG subclasses. Binding of those antibodies to the
      muscle AChR at the neuromuscular junction will trigger the complement-mediated
      destruction of the postsynaptic membrane. Thus, IL-12, a crucial cytokine for
      differentiation of Th1 cells, is necessary for development of EAMG. Th2 cells
      secrete different cytokines, with different effects on the pathogenesis of EAMG.
      Among them, IL-10, which is a potent growth and differentiation factor for B
      cells, facilitates the development of EAMG. In contrast, IL-4 appears to be
      involved in the differentiation of AChR-specific regulatory CD4(+) T cells, which
      can prevent the development of EAMG and its progression to a self-maintaining,
      chronic autoimmune disease. Studies on the AChR-specific CD4(+) cells commonly
      present in the blood of MG patients support a crucial role of CD4(+) T cells in
      the development of MG. Circumstantial evidence supports a pathogenic role of IL
      10 also in human MG. On the other hand, there is no direct or circumstantial
      evidence yet indicating a role of IL-4 in the modulatory or immunosuppressive
      circuits in MG.

PMID- 14592888
TI  - Immunoregulation in experimental autoimmune myasthenia gravis--about T cells,
      antibodies, and endplates.
AB  - Experimental autoimmune myasthenia gravis (EAMG) can be induced in a large number
      of animal species by active immunization (AI) AChR, by passive transfer (PT) of
      anti-AChR antibodies, by autologous bone marrow transplantation and cyclosporin
      (BMT-Cy), or spontaneously. Depending on the model used, different immunological
      mechanisms are operational. In the AI model, the T cell is pivotal in directing
      the anti-AChR antibody production towards pathogenic, that is, cross-linking and
      complement-fixing antibodies. Injection of anti-AChR antibodies alone suffices to
      induce EAMG, excluding the role of specific cell-mediated immune responses in the
      effector phase of the disease. Aged animals are resistant to the induction of AI
      and PT EAMG. This resistance is localized at the postsynaptic membrane containing
      more AChR-anchoring proteins, including S-laminin and rapsyn in aged animals. In
      BMT-CyA EAMG, a dysregulation of the immune system in the absence of immunization
      is capable of inducing myasthenia. The role of these animal models in relation to
      pathogenesis and immunotherapy is discussed.

PMID- 14592889
TI  - Circulating CD4+CD25+ and CD4+CD25- T cells in myasthenia gravis.

PMID- 14592890
TI  - Rationale for a T cell receptor peptide therapy in myasthenia gravis.

PMID- 14592892
TI  - Differences between the epsilon and gamma subunits of the acetylcholine receptor
      (AChR) may be significant in autoimmune myasthenia gravis.

PMID- 14592891
TI  - Antibodies in myasthenia gravis and related disorders.
AB  - Acetylcholine receptor (AChR) antibodies are present in around 85% of patients
      with myasthenia gravis (MG) as measured by the conventional
      radioimmunoprecipitation assay. Antibodies that block the fetal form of the AChR
      are occasionally present in mothers who develop MG after pregnancy, especially in
      those whose babies are born with arthrogryposis multiplex congenita. The
      antibodies cross the placenta and block neuromuscular transmission, leading to
      joint deformities and often stillbirth. In these mothers, antibodies made in the
      thymus are mainly specific for fetal AChR and show restricted germline origins,
      suggesting a highly mutated clonal response; subsequent spread to involve adult
      AChR could explain development of maternal MG in those cases who first present
      after pregnancy. In the 15% of "seronegative" MG patients without AChR antibodies
      (SNMG), there are serum factors that increase AChR phosphorylation and reduce
      AChR function, probably acting via a different membrane receptor. These factors
      are not IgG and could be IgM or even non-Ig serum proteins. In a proportion of
      SNMG patients, however, IgG antibodies to the muscle-specific kinase, MuSK, are
      present. These antibodies are not found in AChR antibody-positive MG and are
      predominantly IgG4. MuSK antibody positivity appears to be associated with more
      severe bulbar disease that can be difficult to treat effectively.

PMID- 14592893
TI  - Use of peptide: HLA class II complexes to study specific T cells in autoimmune
      myasthenia gravis.

PMID- 14592894
TI  - Pathogenesis of myositis and myasthenia associated with titin and ryanodine
      receptor antibodies.
AB  - Some myasthenia gravis (MG) patients have antibodies against skeletal muscle
      antigens in addition to the acetylcholine receptor (AChR). Two major antigens for
      these antibodies are the Ca(2+) release channel of the sarcoplasmic reticulum,
      the ryanodine receptor (RyR), and titin, a gigantic filamentous muscle protein
      essential for muscle structure, function, and development. RyR and titin
      antibodies are found in MG patients with a thymoma and in a proportion of late
      onset MG, and they correlate with severe MG disease. The RyR antibodies recognize
      a region near the N-terminus important for channel regulation. They inhibit
      Ca(2+) release from sarcoplasmic reticulum in vitro. There is
      electrophysiological evidence for a disordered excitation-contraction coupling in
      MG patients. The presence of titin antibodies, which bind to key regions near the
      A/I junction and in the central I-band, correlates with myopathy in MG patients.
      However, so far, there is no direct evidence that antibodies against the
      intracellular antigens RyR and titin are pathogenic in vivo.

PMID- 14592896
TI  - Identification of disease-specific autoantibodies in seronegative myasthenia
      gravis.

PMID- 14592895
TI  - Antibodies in sera of patients with late-onset myasthenia gravis recognize the
      PEVK domain of titin.

PMID- 14592897
TI  - Muscle and neuronal autoantibody markers of thymoma: neurological correlations.

PMID- 14592898
TI  - Susceptibility of ocular tissues to autoimmune diseases.
AB  - The orbital tissues may form a unique immunological environment, as evidenced by
      autoimmune disorders that specifically target orbital tissues, particularly
      myasthenia gravis (MG) and Graves' ophthalmopathy (GO). The reasons for the
      preferential susceptibility are likely to be multiple, based on the interplay of
      molecular and physiological properties of extraocular muscles (EOM), the unique
      requirements of the ocular motor system, and the specific autoimmune pathology.
      Of general importance, even a minor loss of EOM force generation will
      sufficiently misalign the visual axes to produce dramatic symptoms, and
      proprioceptive feedback is limited to overcome such a deficit. Particular to MG,
      EOM synapses appear susceptible to neuromuscular blockade, the autoimmune
      pathology differs between ocular and generalized MG patients, and the influence
      of complement regulatory factors may be less prominent in preventing damage at
      EOM neuromuscular junctions. GO pathogenesis is poorly understood, but shared
      epitopes of orbital fibroblasts, EOM, and thyroid could lead to specific
      autoimmune targeting of these tissues. The differential response of orbital
      fibroblasts to cytokines may be a key factor in disease development. Greater
      appreciation of the immunologic environment of orbital tissues may lead to
      therapies specifically designed for orbital autoimmune diseases.

PMID- 14592899
TI  - Induction of myasthenia gravis in HLA transgenic mice by immunization with human
      acetylcholine receptors.
AB  - We utilized HLA transgenic mice to identify the dominant epitopes on the human
      (H)-AChR alpha subunit. The cytoplasmic H-AChR peptide alpha320-337 was the
      dominant T cell epitope for DQ8, DR3, and DQ8xDQ6 F1 mice. The H-AChR-immunized
      HLA-DQ8, DR3, DQ8xDR3 F1 and DQ8xDQ6 F1 mice developed clinical EAMG, whereas HLA
      DQ6 mice were less susceptible.

PMID- 14592901
TI  - Epitope repertoire of Th1 and Th2 cells reactive with the mouse muscle AChR alpha
      subunit in C57Bl/6 mice.

PMID- 14592900
TI  - Production and characterization of a T cell receptor transgenic mouse recognizing
      the immunodominant epitope of the Torpedo californica acetylcholine receptor.

PMID- 14592902
TI  - Epitope spreading to hidden cytoplasmic regions of the acetylcholine receptor in
      experimental autoimmune myasthenia gravis.

PMID- 14592903
TI  - Immunization with rat-, but not Torpedo-derived 97-116 peptide of the AChR alpha
      subunit induces experimental myasthenia gravis in Lewis rat.

PMID- 14592904
TI  - Effect on T cell recognition and immunogenicity of alanine-substituted peptides
      corresponding to 97-116 sequence of the rat AChR alpha-subunit.

PMID- 14592905
TI  - Characterization of a fully human IgG1 reconstructed from an anti-AChR Fab.

PMID- 14592906
TI  - Roles of complex gangliosides at the neuromuscular junction.

PMID- 14592907
TI  - Role of Munc18-1 in synaptic plasticity at the myasthenic neuromuscular junction.

PMID- 14592908
TI  - The epidemiology of myasthenia gravis.
AB  - Population-based studies of the epidemiology of myasthenia gravis (MG) have been
      conducted for over 50 years. Over that time, there has been a clear trend towards
      an increase in the reported prevalence of the disease. In recent years, there has
      also been an interest in determining a reasonably accurate estimate of the number
      of MG patients in the United States. Current estimates place the prevalence at a
      high value of about 20 per 100,000. The year 2000 U.S. population estimate is
      slightly less than 280 million. A crude estimate of the number of MG patients
      derived from the population estimate and the reported prevalence from selected
      populations indicates that there are between 53,000 and 59,900 patients in the
      United States at this time. The age and ethnic distributions in the United States
      are evolving from those that were present when the majority of the population
      based studies were done, and the distribution of severity of the disease may also
      have changed. Future studies of the epidemiology of MG should take these factors
      into account, and further research into the economic and quality-of-life impact
      of the disease in the population is needed.

PMID- 14592909
TI  - Myasthenia gravis (MG): epidemiological data and prognostic factors.
AB  - Data from 756 myasthenic patients were analyzed for diagnostic criteria, clinical
      aspects, and therapeutic approaches. The patients were followed up at our
      institution from 1981 to 2001. Clinical evaluation was performed according to the
      myasthenia gravis score adopted at our clinic. Clinical features of each patient
      (comprising demographic, clinical, neurophysiological, immunological,
      radiological, and surgical data, as well as serial myasthenia gravis scores) were
      filed in a relational database containing more than 7000 records. Clinical
      efficacy and variables influencing outcome were assessed by life-table methods
      and Cox proportional hazards regression analysis. Complete stable remission, as
      defined by the Task Force of the Medical Scientific Advisory Board of the
      Myasthenia Gravis Foundation of America, was the end point for good prognosis.
      Four hundred and ninety-nine patients (66%) were female and 257 (34%) were male.
      Mean follow-up was 55.1 +/- 48.1 months. Onset of symptoms peaked in the third
      decade in females, whereas the male distribution was bimodal with peaks in the
      third and sixth decades. Modality of myasthenia gravis presentation was as
      follows: ocular, 39.3%; generalized, 28.5%; bulbar, 31.3%; and respiratory, 0.8%.
      Thymectomy was carried out on 63.7% of our patients by different approaches: (1)
      transcervical; (2) transsternal; (3) video-thoracoscopic mini-invasive surgery.
      The last approach has been preferentially used in more recent years and accounted
      for 62.4% of the thymectomized myasthenia gravis population. Univariate analysis
      and Kaplan-Meier analysis showed that variables such as sex (female), age at
      onset (below 40 years), thymectomy, and histological diagnosis of thymic
      hyperplasia were significantly associated with complete stable remission, whereas
      on multivariate analysis only age at onset below 40 years and thymectomy were
      confirmed.

PMID- 14592910
TI  - Myasthenia gravis in individuals over 40.
AB  - Myasthenia gravis (MG) in individuals over 40 years of age comprises three
      groups: early-onset MG with prolonged disease duration, late-onset MG with
      thymoma, and late-onset of nonthymomatous MG. The clinical features do not differ
      between the three groups, except that early-onset patients with prolonged disease
      duration usually have a less severe disease. More than 60% of our MG patients are
      now more than 50 years of age, often with disease onset after age 40. Although 2
      out of the 3 patients in Erb's original description had onset of myasthenic
      symptoms after age 40, this was apparently infrequent in 1879, when the disease
      was first identified. Onset of MG after age 40 is now common. For example, in our
      material, 88/184 (47.8%) had onset of MG after age 40. Eighteen (20.5%) had a
      thymoma. The female:male ratio in the early-onset group was 2.4:1, whereas it was
      1:1.1 among those with onset after age 40. There was no human leukocyte antigen
      association for MG with thymoma. Antibodies to the acetylcholine receptor were
      detected in 88% of sera from nonthymomatous MG and in 100% of those with late
      onset MG with thymoma. Antibodies to titin were found in sera from 85.7% of MG
      patients with thymoma (all age groups) and in 58% of nonthymomatous MG with late
      onset and acetylcholine receptor antibodies. Late-onset, nonthymomatous MG
      comprises two subgroups, one corresponding to delayed early onset and one
      immunologically similar to that seen in patients with MG and thymoma.

PMID- 14592911
TI  - Standards of measurements in myasthenia gravis.
AB  - In 1997, the Medical Scientific Advisory Board of the Myasthenia Gravis
      Foundation of America formed a Task Force to develop classification and outcome
      measures for myasthenia gravis (MG). The goal of the Task Force was to achieve
      uniformity in recording and reporting clinical trials and outcomes research. The
      Task Force met frequently over a three-year period, obtained input from national
      and international experts, and produced a consensus document on recommendations
      for MG clinical research standards. In this article, the essential elements of
      the Task Force's recommendations will be summarized. In addition, several other
      MG measurement tools that are in various stages of development are mentioned.

PMID- 14592912
TI  - A simple manual muscle test for myasthenia gravis: validation and comparison with
      the QMG score.

PMID- 14592913
TI  - Standards of measurements in myasthenia gravis.
AB  - Valid and reliable measurements of muscle impairment are needed to assess
      therapeutic efficacy in patients with generalized myasthenia gravis. Several
      muscle scoring systems have been proposed for assessing muscle strength in such
      patients. The aim of the present study is to assess the validity and
      interobserver agreement of these muscle scores.

PMID- 14592914
TI  - Three forms of immune myasthenia.
AB  - We propose a new classification for immune myasthenia based on antibody pattern.
      The types of immune myasthenia presently characterized by known antibody targets
      segregate into three groups: type 1, in which the muscle target is the
      acetylcholine receptor only; type 2, in which titin antibodies are present in
      addition to acetylcholine receptor antibodies; and type 3, in which muscle
      specific kinase antibodies are present in the absence of acetylcholine receptor
      antibodies. The immune target is unknown in the patients with immune myasthenia
      not associated with these antibodies. This classification has advantages over the
      present classifications as regards homogeneity of groups, etiology, mechanism of
      disease, and prognosis.

PMID- 14592915
TI  - Treatment principles in the management of autoimmune myasthenia gravis.
AB  - The pathogenesis of myasthenia gravis (MG) involves a T cell-directed antibody
      mediated autoimmune attack on the nicotinic acetylcholine receptor (AChR) or,
      occasionally, on other postsynaptic antigens. The antibodies induce their effects
      through complement-mediated destruction of the postsynaptic endplate membrane
      with resultant reduction in endplate AChR, and to a lesser degree by increased
      turnover of endplate AChR or blockade of AChR function. Considerable progress in
      the treatment of MG has accrued from so-called symptomatic treatments, including
      improved critical care of seriously ill patients and medications (e.g.,
      cholinesterase inhibitors) increasing the concentration of acetylcholine at the
      remaining endplate AChRs. Information from other autoimmune diseases and from the
      response of the normal immune system to invading pathogens supports the view that
      the course of MG is characterized by exacerbations and remissions. Therefore, the
      goal in MG treatment is to induce and maintain a remission. This usually involves
      combinations of short-term and long-term immunosuppressive agents. Selection of
      the particular combinations of agents in a given patient is guided by the goal of
      minimizing the cost/benefit ratio of the regimen in an individual patient. In
      general, the plan involves an initial forceful attack followed by a slow and
      measured withdrawal.

PMID- 14592916
TI  - Development of a thymectomy trial in nonthymomatous myasthenia gravis patients
      receiving immunosuppressive therapy.
AB  - Thymectomy has been regularly used in the management of nonthymomatous autoimmune
      myasthenia gravis (MG), but its benefits have not been established in a
      randomized, controlled trial. The widespread use of thymectomy in MG patients
      without thymoma is largely based on retrospective, nonrandomized case series that
      have produced a consensus that the procedure is sometimes beneficial. Still, the
      benefits and utilization of thymectomy are actively debated among MG experts. In
      this paper, we describe the development of a multicenter, international trial to
      determine whether extended transsternal thymectomy reduces corticosteroid
      requirements for patients with generalized AChR antibody-positive nonthymomatous
      MG.

PMID- 14592917
TI  - Thymectomy and antimuscle antibodies in nonthymomatous myasthenia gravis.
AB  - The clinical effect of thymectomy in early- and late-onset myasthenia gravis (MG)
      and the correlation to MG severity, pharmacological treatment, and antimuscle
      antibodies were examined in two series of consecutive acetylcholine receptor
      (AChR) antibody-positive nonthymoma MG patients. The results indicate a benefit
      of thymectomy in early-onset MG, but no obvious clinical benefit in late-onset
      MG. The presence of muscle autoantibodies did not influence the outcome of
      thymectomy in early-onset MG. In late-onset MG, improvement is least likely in
      patients with titin and/or RyR antibodies. Thymectomy should always be considered
      shortly after MG onset in early-onset MG patients and might only be considered in
      late-onset patients who have early-onset-like immunological characteristics.

PMID- 14592918
TI  - Prognostic factors of thymectomy in patients with myasthenia gravis: a cohort of
      132 patients.

PMID- 14592919
TI  - Mycophenolate mofetil for myasthenia gravis: a double-blind, placebo-controlled
      pilot study.
AB  - Mycophenolate mofetil (MM) is an immunosuppressive agent developed and originally
      used to prevent acute rejection of solid-organ transplantation. There have been
      preliminary reports of its successful use in the treatment of autoimmune
      myasthenia gravis (MG). We conducted a double-blind, placebo-controlled pilot
      trial of MM in the treatment of suboptimally controlled, stable MG. Results of
      this pilot study are promising and suggestive of greater improvement in the
      patients who received MM compared to placebo.

PMID- 14592920
TI  - Lambert-eaton myasthenic syndrome: diagnosis and treatment.
AB  - A high index of suspicion is essential in arriving at the correct diagnosis of
      Lambert-Eaton myasthenic syndrome (LEMS). LEMS should be considered in the
      differential in any patient who has proximal weakness, reduced or absent muscle
      stretch reflexes, and dry mouth. Weakness predominates in hip and shoulder
      muscles, but may also affect ocular and oropharyngeal muscles to a lesser extent.
      The diagnosis is confirmed by demonstrating characteristic electromyographic
      findings-low-amplitude muscle responses that increase dramatically after
      activation. Most patients also have circulating antibodies to the voltage-gated
      calcium channel. Half the patients with LEMS have a malignancy, usually small
      cell lung cancer. The diagnosis should trigger an intensive search for
      malignancy, especially in older patients with a history of smoking. Younger,
      nonsmoking patients are likely to have LEMS as part of a more general autoimmune
      state. Successful treatment of the underlying cancer leads to improvement in many
      patients. More than 85% of patients have clinically significant benefit from 3,4
      diaminopyridine (DAP). In over half of these, the improvement is marked. If
      severe weakness persists despite DAP, immunotherapy should be considered. Plasma
      exchange and high-dose immunoglobulin induce transient improvement in many
      patients, but function rarely becomes normal. Combinations of prednisone,
      azathioprine, or cyclosporine have been used with variable success. Improvement,
      if any, occurs only after many months and requires chronic administration of
      immunosuppressive medications at significant doses. The long-term prognosis in
      LEMS is determined by the presence of cancer or other autoimmune disease.

PMID- 14592921
TI  - Abnormal single-fiber electromyography in patients not having myasthenia: risk
      for diagnostic confusion?

PMID- 14592922
TI  - Treatment of autoimmune disease by adoptive cellular gene therapy.
AB  - Autoimmune disorders represent inappropriate immune responses directed at self
      tissue. Antigen-specific CD4+ T cells and antigen-presenting dendritic cells
      (DCs) are important mediators in the pathogenesis of auto-immune disease and thus
      are ideal candidates for adoptive cellular gene therapy, an ex vivo approach to
      therapeutic gene transfer. Using retrovirally transduced cells and luciferase
      bioluminescence, we have demonstrated that primary T cells, T cell hybridomas,
      and DCs rapidly and preferentially home to the sites of inflammation in animal
      models of multiple sclerosis, arthritis, and diabetes. These cells, transduced
      with retroviral vectors to drive expression of various "regulatory proteins" such
      as IL-4, IL-10, IL-12p40, and anti-TNF scFv, deliver these immunoregulatory
      proteins to the inflamed lesions, providing therapy for experimental autoimmune
      encephalitis (EAE), collagen-induced arthritis (CIA), and nonobese diabetic mice
      (NOD).

PMID- 14592924
TI  - Suppression of myasthenia gravis by antigen-specific mucosal tolerance and
      modulation of cytokines and costimulatory factors.
AB  - We have shown that mucosal administration of recombinant fragments corresponding
      to the human acetylcholine receptor (AChR) alpha subunit suppresses chronic
      ongoing experimental autoimmune myasthenia gravis (EAMG) in rats. Treated animals
      exhibit a Th1 to Th2/Th3 shift in their cytokine profile and downregulation of
      costimulatory factors. However, application of a xenogeneic recombinant fragment
      may have limitations when considered as a possible approach for the treatment of
      MG in humans. We therefore tested the potential of a syngeneic fragment and of
      long synthetic peptides to suppress EAMG. We found that a syngeneic fragment
      corresponding to the extracellular region of the rat AChR alpha subunit was as
      effective as the formerly described human xenogeneic fragment in suppressing
      ongoing EAMG. This is encouraging in view of the potential use of mucosally
      administered recombinant AChR fragments for the treatment of MG in humans.
      However, in severely affected individuals, this antigen-specific approach may
      need to be supported by direct modulation of cytokines and costimulatory factors
      known to be involved in the pathogenesis of EAMG. To test the potential of this
      approach, myasthenic rats were injected by antibodies either to the
      proinflammatory cytokine IL-18 or to the costimulatory factor CD40L. These
      treatments act via different mechanisms, but both lead to the alleviation of
      clinical symptoms even when given at the chronic phase of EAMG. We suggest that
      antagonists to key cytokines and/or costimulatory factors be used to augment
      antigen-specific treatments of myasthenia such as mucosal administration of AChR
      recombinant fragments.

PMID- 14592925
TI  - Suppression of EAMG in Lewis rats by IL-10-exposed dendritic cells.

PMID- 14592923
TI  - Specific immunotherapy of experimental myasthenia by genetically engineered APCs:
      the "guided missile" strategy.
AB  - Although treatment of MG with general immunosuppressive agents is often
      effective, it has important drawbacks, including suppression of the immune system
      as a whole, with the risks of infection and neoplasia, and numerous other adverse
      side effects. Ideally, treatment of MG should eliminate the specific pathogenic
      autoimmune response to AChR, without otherwise suppressing the immune system or
      producing other adverse side effects. Although antibodies to AChR are directly
      responsible for the loss of AChRs at neuromuscular junctions in MG, the AChR
      antibody response is T cell-dependent, and immunotherapy directed at T cells can
      abrogate the autoantibody response, with resulting benefit. As in other
      autoimmune diseases, the T cell response in MG is highly heterogeneous. The
      design of specific immunotherapy must take this heterogeneity into account and
      target the entire repertoire of AChR-specific T cells. We describe our
      investigation of a novel strategy for specific immunotherapy of MG, involving
      gene transfer to convert antigen-presenting cells (APCs) to "guided missiles"
      that target AChR-specific T cells, and that induce apoptosis and elimination of
      those T cells. This strategy uses the ability of APCs from a given individual to
      present the entire spectrum of AChR epitopes unique for that individual, and
      thereby to target the entire repertoire of antigen-specific T cells of the same
      individual. Using viral vectors, we have genetically engineered the APCs to
      process and present the most important domain of the AChR molecule, and to
      express a "warhead" of Fas ligand (FasL) to eliminate the activated AChR-specific
      T cells with which they interact. Our results show that the APCs express the
      appropriate gene products, and effectively and specifically eliminate AChR
      specific T cells by the Fas/FasL pathway, while sparing T cells of other
      specificities.

PMID- 14592926
TI  - Future therapeutic strategies in autoimmune myasthenia gravis.
AB  - Antibodies against muscle acetylcholine receptor (AChR) undoubtedly play a
      critical role in the pathology of most myasthenia gravis (MG) cases. Selective
      elimination of the majority of these antibodies should result in a considerable
      improvement of the MG symptoms. Such a specific elimination could be achieved by
      AChR-based immunoadsorbents. However, sufficient quantities of native human AChR
      are not available while bacterially expressed recombinant domains of the AChR are
      unable to bind satisfactorily MG antibodies. We have undertaken the production of
      the extracellular domains of human AChR subunits in eukaryotic systems, in native
      like conformation, for their use as potent immunoadsorbents. The N-terminal
      extracellular domain (amino acids 1-210; alpha(1-210)) of the alpha(1) subunit of
      the human muscle AChR was expressed in the yeast Pichia pastoris. The polypeptide
      was water-soluble, glycosylated, and in monomer form. The alpha(1-210) bound 125I
      alpha-bungarotoxin (125I-alpha-BTX) with a high affinity (Kd = 5.1 +/- 2.4 nM),
      and this binding was blocked by unlabeled d-tubocurarine and gallamine. Several
      conformation-dependent anti-AChR antibodies were able to bind alpha(1-210) as did
      antibodies from a large proportion of MG patients. The purified protein was
      subsequently immobilized on Sepharose-CNBr and was used to immunoadsorb anti-AChR
      antibodies from 64 MG sera. It eliminated more than 50% (50-94%) of the anti-AChR
      antibodies in 20% of the sera, whereas from another 30% of the sera it eliminated
      20-60% of their anti-AChR antibodies. Work is in progress for the expression of
      the extracellular domain of all other muscle AChR subunits. It is expected that
      their combined use may eliminate the great majority of the anti-AChR antibodies
      from most MG patients.

PMID- 14592927
TI  - Attenuated innate mechanisms of interferon-gamma production in rats susceptible
      to postviral airway dysfunction.
AB  - After Sendai virus (SeV)-induced bronchiolitis as weanlings, BN, but not F344,
      rats develop a postbronchiolitis asthma-like phenotype, which can be prevented by
      supplemental interferon (IFN)-gamma treatment. We have shown that splenocytes
      from BN weanlings, compared with those from F344 weanlings, have a markedly
      reduced capacity for IFN-gamma production. We hypothesized that SeV-induced IFN
      gamma production occurs via innate mechanisms that are attenuated in BN
      weanlings. Therefore, we investigated potential mechanisms of SeV-induced IFN
      gamma production in BN and F344 weanlings. SeV-stimulated splenocytes secreted
      the IFN-gamma-inducing cytokines, interleukin (IL)-12 and IL-18. BN splenocytes
      produced significantly less IL-12 (P = 0.001) and IL-18 (P < 0.001) than did F344
      splenocytes. Depletion studies demonstrated that natural killer cells were the
      primary source of SeV-induced IFN-gamma production. Anti-IL-12 antibody, IL-12
      p40 homodimer, and IL-18 binding protein each inhibited SeV-induced IFN-gamma
      production by 82-94%, and the combination of IL-12 p40 homodimer and IL-18
      binding protein abolished SeV-induced IFN-gamma production, demonstrating
      synergism between IL-12 and IL-18. Therefore, SeV-induced IFN-gamma production
      occurred via innate IL-12-, IL-18-, and natural killer cell-dependent mechanisms,
      which were attenuated in BN weanlings. Attenuation of innate IFN-gamma-producing
      responses to SeV in BN weanlings may be a critical factor in their susceptibility
      to postbronchiolitis chronic airway dysfunction.

PMID- 14592928
TI  - Mucin biosynthesis: bovine C2GnT-M gene, tissue-specific expression, and herpes
      virus-4 homologue.
AB  - Mucin glycans are the major determinant of mucin functions. Mucin glycan branch
      structures, which increase structural heterogeneity and thus functional
      potential, are extended from beta6 N-acetylglucosaminides formed by beta6 N
      acetylglucosaminyltransferases (beta6GnT). Core 2 beta6GnT-M (C2GnT-M) is the
      only branching enzyme that can synthesize all known mucin beta6 N
      acetylglucosaminides. We report the cloning of four different bovine (b) C2GnT-M
      transcripts that are different only at 5'-untranslated regions. Two bC2GnT-M
      transcripts are found exclusively in tracheal epithelium and testis, whereas the
      other two are found in all other mucus-secreting tissues. The bC2GnT-M gene
      contains four exons spanning 5.3 kb, and the entire open reading frame is in one
      exon. The bC2GnT-M ORF has 95, 83, and 75% sequence identity to those of bovine
      herpes virus type 4 (BHV-4), human, and rat C2GnT-Ms, respectively. The homology
      between bovine and BHV-4 C2GnT-M genes is in the region between 170 nucleotides
      upstream from ATG start codon and 114 nucleotides downstream from TGA stop codon
      of the viral gene. Localized at the nonconserved region of the viral genome, the
      BHV-4 C2GnT-M gene is the only known viral C2GnT-M gene. The results suggest that
      BHV-4 acquired its C2GnT-M gene from the bovine gene. The mechanism of the viral
      acquisition of bC2GnT-M gene and the roles of the C2GnT-M gene in the survival
      and pathogenesis of this virus remain to be elucidated.

PMID- 14592929
TI  - Hemodynamic effects of blood loss during a passive response to a stressor in the
      conscious rabbit.
AB  - In the conscious rabbit, exposure to an air jet stressor increases arterial
      pressure, heart rate, and cardiac output. During hemorrhage, air jet exposure
      extends the blood loss necessary to produce hypotension. It is possible that this
      enhanced defense of arterial pressure is a general characteristic of stressors.
      However, some stressors such as oscillation (OSC), although they increase
      arterial pressure, do not change heart rate or cardiac output. The cardiovascular
      changes during OSC resemble those seen during freezing behavior. In the present
      study, our hypothesis was that, unlike air jet, OSC would not affect defense of
      arterial blood pressure during blood loss. Male New Zealand White rabbits were
      chronically prepared with arterial and venous catheters and Doppler flow probes.
      We removed venous blood until mean arterial pressure decreased to 40 mmHg. We
      repeated the experiment in each rabbit on separate days in the presence and
      absence (SHAM) of OSC. Compared with SHAM, OSC increased arterial pressure 14 +/-
      1 mmHg, central venous pressure 3.3 +/- 0.4 mmHg, and hindquarter blood flow 34
      +/- 4% while decreasing mesenteric conductance 32 +/- 3% and not changing heart
      rate or cardiac output. During normotensive hemorrhage, OSC enhanced hindquarter
      and renal vasoconstriction. Contrary to our hypothesis, OSC (23.5 +/- 0.6 ml/kg)
      increased the blood loss necessary to produce hypotension compared with SHAM
      (16.8 +/- 0.6 ml/kg). In nine rabbits, OSC prevented hypotension even after a
      blood loss of 27 ml/kg. Thus a stressful stimulus that resulted in cardiovascular
      changes similar to those seen during freezing behavior enhanced defense of
      arterial pressure during hemorrhage.

PMID- 14592930
TI  - Divergent gonadotropin-gonadal dose-responsive coupling in healthy young and
      aging men.
AB  - The present study extends a recent composite model of in vivo interglandular
      signaling to assess the impact of age on 1) nonequilibrium exchange among
      diffusible and protein-bound testosterone (Te); 2) elimination of total and free
      Te; 3) basal and pulsatile Te secretion (sec); 4) the implicit feedforward
      function mediating luteinizing hormone (LH) concentration (con) drive of
      instantaneous Te sec; and 5) possible stochastic variability of the predicted LH
      con-Te sec dose-response linkage. To this end, we measured LH and Te con every 10
      min for 24 h in healthy young (n = 13) and older men (n = 13). Statistical
      comparisons of analytic estimates revealed that elderly subjects manifest 1)
      reduced maximal burstlike LH-stimulated Te sec (impaired stimulus efficacy); 2)
      depressed half-maximally LH-stimulated Te sec (lower Leydig-cell responsivity);
      3) decreased pulsatile and total Te sec; 4) elevated basal Te sec; 5) a prolonged
      half-life of total but not free Te con; and 6) delayed time evolution of LH and
      Te sec bursts. In contradistinction, age did not influence estimated LH-pulse
      potency (ED50), steroidogenic sensitivity (slope term), or stochastic variability
      of LH-Te coupling. On the basis of these data, we postulate that aging in the
      human male alters specific dose-response attributes linking LH con and Te sec and
      disrupts the time waveform of LH and Te sec bursts.

PMID- 14592931
TI  - Neuroprotection by tempol in a model of iron-induced oxidative stress in acute
      ischemic stroke.
AB  - Studies suggest iron exacerbates the damage caused by ischemic stroke. Our aim
      was to elucidate the effect of iron overload on infarct size after middle
      cerebral artery occlusion (MCAO) and to evaluate the efficacy of tempol, a
      superoxide dismutase mimetic, as a neuroprotective agent. Rats were administered
      iron +/- tempol before MCAO; control rats received saline. The middle cerebral
      artery was occluded for 24 h, and the size of the resultant infarct was assessed
      and expressed as the percentage of the hemisphere infracted (%HI). Iron treatment
      increased infarct size compared with control (51.83 +/- 3.55 vs. 27.56 +/-
      3.28%HI iron treated vs. control, P = 0.01); pretreatment with tempol reversed
      this (51.83 +/- 3.55 vs. 26.09 +/- 9.57%HI iron treated vs. iron + tempol
      treated, P = 0.02). We hypothesized that reactive oxygen species (ROS) were
      responsible for the iron-induced damage. We measured ROS generated by exogenous
      iron in brain and peripheral vasculature from rats that had not undergone MCAO.
      There was no increase in ROS production in the brain of iron-treated rats or in
      brain slices incubated with iron citrate. However, ROS generation in carotid
      arteries incubated with iron citrate was significantly increased. ROS generation
      from the brain was assessed after MCAO by dihydroethidine staining; there was a
      dramatic increase in the ROS generation by the brain in the iron-treated rats
      compared with control 30 min after MCAO. We propose that iron-induced ROS
      generation in the cerebral vasculature adds to oxidative stress during an
      ischemic episode after the disruption of the blood-brain barrier.

PMID- 14592932
TI  - Baroreflexes of the rat. III. Open-loop gain and electroencephalographic arousal.
AB  - In early studies of humans, baroreflex sensitivity was found to be higher during
      sleep; however, subsequent observations in several species, including humans,
      have been at variance with the original reports. Sleep and arousal are behavioral
      states, and it is difficult to accurately and repeatedly measure baroreflex
      sensitivity in behaving animals. However, pharmacologically immobilized
      (neuromuscularly blocked) rats have apparently normal sleep-wakefulness cycles,
      and baroreflex gain can be measured directly in this preparation. Using the delta
      band of the EEG (EEG(delta)) as an index of sleep and arousal and open-loop
      aortic depressor nerve (ADN) stimulation as a baroreflex input, we found that
      blood pressure (BP) level depended on arousal (r = -0.416; P < 0.0001), and BP
      baroreflex gain depended on BP level (r = 0.496; P < 0.0001), but that BP
      baroreflex gain was independent of arousal (r = 0.001; NS). Heart period (HP) was
      different; although HP level depended on arousal (r = 0.352; P < 0.0001), HP
      baroreflex gain did not depend on HP level (r = 0.029; NS), and HP baroreflex
      gain increased with arousal (r = 0.315; P < 0.0001). A partial-correlations
      analysis showed that the presence of the relationship between BP level and BP
      baroreflex gain probably attenuated the relationship between arousal and BP gain.
      The results are consistent 1) with physiological findings showing that arousal
      attenuates afferent transmission through the nucleus of the solitary tract and
      enhances sympathoinhibition at the rostral ventrolateral medulla; and 2) with
      observations in humans and animals showing increased cardiac baroreflex
      sensitivity during sleep, but little if any effect of sleep on BP baroreflex
      sensitivity. The findings are relevant to all methods of baroreflex gain
      estimation that use HP as the index of baroreflex activation.

PMID- 14592933
TI  - Mice bearing Acads mutation display altered postingestive but not 5-s orosensory
      response to dietary fat.
AB  - A previous survey of mouse inbred strains revealed a wide range in self-selected
      fat intake, from 26 to 83% of energy. The BALB/cByJ strain selected a lower
      percentage of fat intake (36%) than all other strains tested except for the
      CAST/Ei. BALB/cByJ mice are deficient in the short-chain acyl-CoA dehydrogenase
      (SCAD) enzyme due to a spontaneous mutation in Acads. We hypothesized that this
      deficiency would alter fat appetite and used three behavioral test paradigms to
      compare the response of BALB/cByKz. Acads -/- and BALB/cByKz. Acads +/+ mice to
      fat stimuli. First, during 10-day exposure to a macronutrient self-selection
      diet, Acads -/- mice consumed proportionately less fat and more carbohydrate than
      Acads +/+ mice, yet total energy intake was similar between strains. Next, in 48
      h two-bottle preference tests, Acads +/+ mice displayed a preference for 50% corn
      oil, but Acads -/- mice did not. Finally, in brief-access taste tests employing
      successive 5-s presentations of corn oil in an ascending concentration series
      ending with 50%, there were no effects of strain on total licks, indicating that
      Acads does not alter acute orosensory response to this fat stimulus. With 15-s
      presentations, however, the Acads +/+ mice licked more of the 50% oil than Acads 
      /-, suggesting orosensory effects related to the increased exposure time. In
      contrast to corn oil, there were no strain differences in licking response to
      sucrose solution in either the two-bottle or brief-access taste tests. The
      observation that SCAD-deficient mice display altered postingestive responses to
      dietary fat provides further evidence for the metabolic control of feeding.

PMID- 14592934
TI  - Regulation of action potential duration under acute heat stress by I(K,ATP) and
      I(K1) in fish cardiac myocytes.
AB  - The mechanism underlying temperature-dependent shortening of action potential
      (AP) duration was examined in the fish (Carassius carassius L.) heart ventricle.
      Acute temperature change from +5 to +18 degrees C (heat stress) shortened AP
      duration from 2.8 +/- 0.3 to 1.3 +/- 0.1 s in intact ventricles. In 56% (18 of
      32) of enzymatically isolated myocytes, heat stress also induced reversible
      opening of ATP-sensitive K+ channels and increased their single-channel
      conductance from 37 +/- 12 pS at +8 degrees C to 51 +/- 13 pS at +18 degrees C
      (Q10 = 1.38) (P < 0.01; n = 12). The ATP-sensitive K+ channels of the crucian
      carp ventricle were characterized by very low affinity to ATP both at +8 degrees
      C [concentration of Tris-ATP that produces half-maximal inhibition of the channel
      (K1/2)= 1.35 mM] and +18 degrees C (K1/2 = 1.85 mM). Although acute heat stress
      induced ATP-sensitive K+ current (IK,ATP) in patch-clamped myocytes, similar heat
      stress did not cause any glibenclamide (10 microM)-sensitive changes in AP
      duration in multicellular ventricular preparations. Examination of APs and K+
      currents from the same myocytes by alternate recording under current-clamp and
      voltage-clamp modes revealed that changes in AP duration were closely correlated
      with temperature-specific changes in the voltage-dependent rectification of the
      background inward rectifier K+ current IK1. In approximately 15% of myocytes (4
      out of 27), IK,ATP-dependent shortening of AP followed the IK1-induced AP
      shortening. Thus heat stress-induced shortening of AP duration in crucian carp
      ventricle is primarily dependent on IK1. IK,ATP is induced only in response to
      prolonged temperature elevation or perhaps in the presence of additional
      stressors.

PMID- 14592935
TI  - Short-term CR decreases cardiac mitochondrial oxidant production but increases
      carbonyl content.
AB  - Lifelong caloric restriction (CR) reduces the rate of mitochondrial oxidant
      production and the accumulation of oxidized proteins and prevents some of the age
      associated decline in 20S proteasome activity. However, few studies have
      investigated how rapidly the beneficial effects of CR take place. We investigated
      whether 2 mo of CR in 6-mo-old rats would be of sufficient duration to elicit
      these beneficial changes. Mitochondrial oxidant production was significantly
      diminished in the CR rats compared with the ad libitum-fed animals. Short-term CR
      also caused a significant decrease in mitochondrial superoxide dismutase (SOD)
      and glutathione peroxidase (GPX) activities, but there were no differences in
      cytosolic SOD and GPX activities, whereas mitochondrial and cytosolic catalase
      (CAT) activity was increased with CR. However, protein carbonyl content was
      significantly elevated in both the mitochondrial and cytosolic fractions from CR
      rats. Of the three major 20S proteasome activities (chymotrypsin-like, trypsin
      like, and peptidylglutamyl-peptide hydrolase), the peptidylglutamyl-peptide
      hydrolase activity was significantly elevated in the CR animals, possibly because
      of the fact that there were more oxidized proteins to be degraded. Although fewer
      oxidants were produced in the CR animals, it is possible that the ability to
      scavenge oxidants was transiently suppressed because of the reduction in
      mitochondrial antioxidant enzyme activities, which may explain the observed
      increases in carbonyl content.

PMID- 14592936
TI  - p38gamma MAPK regulation of glucose transporter expression and glucose uptake in
      L6 myotubes and mouse skeletal muscle.
AB  - Skeletal muscle expresses at least three p38 MAPKs (alpha, beta, gamma). However,
      no studies have examined the potential regulation of glucose uptake by p38gamma,
      the isoform predominantly expressed in skeletal muscle and highly regulated by
      exercise. L6 myotubes were transfected with empty vector (pCAGGS), activating
      MKK6 (MKK6CA), or p38gamma-specific siRNA. MKK6CA-transfected cells had higher
      rates of basal 2-deoxy-d-[3H]glucose (2-DG) uptake (P < 0.05) but lower rates of
      2,4-dinitrophenol (DNP)-stimulated glucose uptake, an uncoupler of oxidative
      phosphorylation that operates through an insulin-independent mechanism (P <
      0.05). These effects were reversed when MKK6CA cells were cotransfected with
      p38gamma-specific siRNA. To determine whether the p38gamma isoform is involved in
      the regulation of contraction-stimulated glucose uptake in adult skeletal muscle,
      the tibialis anterior muscles of mice were injected with pCAGGS or wild-type
      p38gamma (p38gammaWT) followed by intramuscular electroporation. Basal and
      contraction-stimulated 2-DG uptake in vivo was determined 14 days later.
      Overexpression of p38gammaWT resulted in higher basal rates of glucose uptake
      compared with pCAGGS (P < 0.05). Muscles overexpressing p38gammaWT showed a trend
      for lower in situ contraction-mediated glucose uptake (P = 0.08) and
      significantly lower total GLUT4 levels (P < 0.05). These data suggest that
      p38gamma increases basal glucose uptake and decreases DNP- and contraction
      stimulated glucose uptake, partially by affecting levels of glucose transporter
      expression in skeletal muscle. These findings are consistent with the hypothesis
      that activation of stress kinases such as p38 are negative regulators of
      stimulated glucose uptake in peripheral tissues.

PMID- 14592937
TI  - Effect of stent coating alone on in vitro vascular smooth muscle cell
      proliferation and apoptosis.
AB  - Synthetic polymers, like methacrylate (MA) compounds, have been clinically
      introduced as inert coatings to locally deliver drugs that inhibit restenosis
      after stent. The aim of the present study was to evaluate the effects of MA
      coating alone on vascular smooth muscle cell (VSMC) growth in vitro. Stainless
      steel stents were coated with MA at the following doses: 0.3, 1.5, and 3 ml.
      Uncoated/bare metal stents were used as controls. VSMCs were cultured in dishes,
      and a MA-coated stent or an uncoated bare metal stent was gently added to each
      well. VSMC proliferation was assessed by bromodeoxyuridine (BrdU) incorporation.
      Apoptosis was analyzed by three distinct approaches: 1) annexin V/propidium
      iodide fluorescence detection; 2) DNA laddering; and 3) caspase-3 activation and
      PARP cleavage. MA-coated stents induced a significant decrease of BrdU
      incorporation compared with uncoated stents at both the low and high
      concentrations. In VSMCs incubated with MA-coated stents, annexin V/propidium
      iodide fluorescence detection showed a significant increase in apoptotic cells,
      which was corroborated by the typical DNA laddering. Apoptosis of VSMCs after
      incubation with MA-coated stents was characterized by caspase-3 activation and
      PARP cleavage. The MA-coated stent induced VSMC growth arrest by inducing
      apoptosis in a dose-dependent manner. Thus MA is not an inert platform for
      eluting drugs because it is biologically active per se. This effect should be
      taken in account when evaluating an association of this coating with
      antiproliferative agents for in-stent restenosis prevention.

PMID- 14592938
TI  - A theoretical model of nitric oxide transport in arterioles: frequency- vs.
      amplitude-dependent control of cGMP formation.
AB  - Nitric oxide (NO) plays many important physiological roles, including the
      regulation of vascular smooth muscle tone. In response to hemodynamic or agonist
      stimuli, endothelial cells produce NO, which can diffuse to smooth muscle where
      it activates soluble guanylate cyclase (sGC), leading to cGMP formation and
      smooth muscle relaxation. The close proximity of red blood cells suggests,
      however, that a significant amount of NO released will be scavenged by blood, and
      thus the issue of bioavailability of endothelium-derived NO to smooth muscle has
      been investigated experimentally and theoretically. We formulated a mathematical
      model for NO transport in an arteriole to test the hypothesis that transient,
      burst-like NO production can facilitate efficient NO delivery to smooth muscle
      and reduce NO scavenging by blood. The model simulations predict that 1) the
      endothelium can maintain a physiologically significant amount of NO in smooth
      muscle despite the presence of NO scavengers such as hemoglobin and myoglobin; 2)
      under certain conditions, transient NO release presents a more efficient way for
      activating sGC and it can increase cGMP formation severalfold; and 3) frequency
      rather than amplitude-dependent control of cGMP formation is possible. This
      suggests that it is the frequency of NO bursts and perhaps the frequency of
      Ca(2+) oscillations in endothelial cells that may limit cGMP formation and
      regulate vascular tone. The proposed hypothesis suggests a new functional role
      for Ca(2+) oscillations in endothelial cells. Further experimentation is needed
      to test whether and under what conditions in silico predictions occur in vivo.

PMID- 14592939
TI  - Roles for alphaB-crystallin and HSPB2 in protecting the myocardium from ischemia
      reperfusion-induced damage in a KO mouse model.
AB  - Overexpression studies have shown that the small heat shock proteins (sHSP)
      protect the myocardium from ischemia-reperfusion (I/R)-induced damage. However,
      gene deletion studies are necessary to demonstrate whether sHSPs are required for
      protection. The genes for alphaB-crystallin (alphaBC) and HSPB2, two sHSPs that
      are expressed in high levels in the heart, are in close proximity to one another;
      as a result, both genes were disrupted in a recently generated knockout (KO)
      mouse line. The alphaBC/HSPB2 KO mouse line is currently the only model that
      features disruption of sHSPs normally expressed in the heart. Accordingly, we
      examined the cardiac morphology, function, and response to I/R-induced stress in
      alphaBC-HSPB2 KO mice. Initial gross, light microscopic and echocardiographic
      characterization showed that the morphological and functional properties of
      hearts from adult KO mice were indistinguishable from age-matched wild-type (WT)
      mice. Electron microscopy showed that, compared with WT mouse hearts, KO mouse
      heart sarcomeres were relatively normal. Isolated perfused KO mouse hearts
      displayed normal contractility; however, when compared with WT, after I/R, KO
      mouse hearts exhibited a twofold reduction in contractile recovery, as well as
      increased necrosis and apoptosis. Additionally, when compared with WT, KO mouse
      hearts exhibited 43% less reduced glutathione, which is known to protect from I/R
      induced damage. Thus, whereas neither alphaBC nor HSPB2 is essential for
      myocardial development and function under nonstressful conditions, one or both
      are required for maximal functional recovery and protection from I/R-induced
      necrosis and apoptosis.

PMID- 14592940
TI  - ROS are required for rapid reactivation of Na+/Ca2+ exchanger in hypoxic
      reoxygenated guinea pig ventricular myocytes.
AB  - The cardiac Na(+)/Ca(2+) exchanger (NCX) contributes to cellular injury during
      hypoxia, as its altered function is largely responsible for a rise in cytosolic
      Ca(2+) concentration ([Ca(2+)](i)). In addition, the NCX in guinea pig
      ventricular myocytes undergoes profound inhibition during hypoxia and rapid
      reactivation during reoxygenation. The mechanisms underlying these changes in NCX
      activity are likely complex due to the participation of multiple inhibitory
      factors including altered cytosolic Na(+) concentration, pH, and ATP. Our main
      hypothesis is that oxidative stress is an essential trigger for rapid NCX
      reactivation in guinea pig ventricular myocytes and is thus a critical factor in
      determining the timing and magnitude of Ca(2+) overload. This hypothesis was
      evaluated in cardiac myocytes using fluorescent indicators to measure [Ca(2+)](i)
      and oxidative stress. An NCX antisense oligonucleotide was used to decrease NCX
      protein expression in some experiments. Our results indicate that NCX activity is
      profoundly inhibited in hypoxic guinea pig ventricular myocytes but is
      reactivated within 1-2 min of reoxygenation at a time of rising oxidative stress.
      We also found that several interventions to decrease oxidative stress including
      antioxidants and diazoxide prevented NCX reactivation and Ca(2+) overload during
      reoxygenation. Furthermore, application of exogenous H(2)O(2) was sufficient by
      itself to reactivate the NCX during sustained hypoxia and could reverse the
      suppression of reoxygenation-mediated NCX reactivation by diazoxide. These data
      suggest that elevated oxidative stress in reoxygenated guinea pig ventricular
      myocytes is required for rapid NCX reactivation, and thus reactivation should be
      viewed as an active process rather than being due to the simple decline of NCX
      inhibition.

PMID- 14592941
TI  - Pyrimidine nucleotides suppress KDR currents and depolarize rat cerebral arteries
      by activating Rho kinase.
AB  - This study examined whether, and by what signaling and ionic mechanisms,
      pyrimidine nucleotides constrict rat cerebral arteries. Cannulated cerebral
      arteries stripped of endothelium and pressurized to 15 mmHg constricted in a dose
      dependent manner to UTP. This constriction was partly dependent on the
      depolarization of smooth muscle cells and the activation of voltage-operated
      Ca(2+) channels. The depolarization and constriction induced by UTP were
      unaffected by bisindolylmaleimide I, a PKC inhibitor that abolished phorbol ester
      (PMA)-induced constriction in cerebral arteries. In contrast, the Rhokinase
      inhibitor Y-27632 attenuated the ability of UTP to both constrict and depolarize
      cerebral arteries. With patch-clamp electrophysiology, a voltage-dependent
      delayed rectifying K(+) (K(DR)) current was isolated and shown to consist of a
      slowly inactivating 4-aminopyridine (4-AP)-sensitive and an -insensitive
      component. The 4-AP-sensitive K(DR) current was potently suppressed by UTP
      through a mechanism that was not dependent on PKC. This reflects observations
      that demonstrated that 1) a PKC activator (PMA) had no effect on K(DR) and 2) PKC
      inhibitors (calphostin C or bisindolylmaleimide I) could not prevent the
      suppression of K(DR) by UTP. The Rho kinase inhibitor Y-27632 abolished the
      ability of UTP to inhibit the K(DR) current, as did inhibition of RhoA with C3
      exoenzyme. Cumulatively, these observations indicate that Rho kinase signaling
      plays an important role in eliciting the cerebral constriction induced by
      pyrimidine nucleotides. Moreover, they demonstrate for the first time that
      Rhokinase partly mediates this constriction by altering ion channels that control
      membrane potential and Ca(2+) influx through voltage-operated Ca(2+) channels.

PMID- 14592942
TI  - Novel anti-inflammatory actions of amlodipine in a rat model of arteriosclerosis
      induced by long-term inhibition of nitric oxide synthesis.
AB  - Amlodipine (a new class of calcium channel antagonist) has been shown to limit
      the progression of arteriosclerosis and decrease the incidence of cardiovascular
      events. The mechanisms underlying the beneficial effects of amlodipine, however,
      remain unclear. Therefore, we hypothesized that amlodipine attenuates the
      development of arteriosclerosis through the inhibition of inflammation in vivo.
      Long-term inhibition of nitric oxide (NO) by administration of a NO synthase
      inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME), to rats induces
      coronary vascular inflammation [monocyte infiltration, monocyte chemoattractant
      protein-1 (MCP-1) expression, increased activity of angiotensin-converting enzyme
      (ACE)], and arteriosclerosis. Here, we used the rat model to investigate the anti
      inflammatory effects of amlodipine in vivo. Treatment with amlodipine markedly
      inhibited the L-NAME-induced increase in vascular inflammation, oxidative stress,
      and local ACE and Rho activity and prevented arteriosclerosis. Interestingly,
      amlodipine prevented the L-NAME-induced increase in MCP-1 receptor CCR2
      expression in circulating monocytes. Amlodipine markedly attenuated the high
      mortality rate at 8 wk of treatment. These data suggest that amlodipine
      attenuated arteriosclerosis through inhibiting inflammatory disorders in the rat
      model of long-term inhibition of NO synthesis. The anti-inflammatory effects of
      amlodipine seem to be mediated not only by the inhibition of local factors such
      as MCP-1 but also by the decrease in CCR2 in circulating monocytes. Inhibition of
      the MCP-1 to CCR2 pathway may represent novel anti-inflammatory actions of
      amlodipine beyond blood pressure lowering.

PMID- 14592943
TI  - Demonstration of functional role of TECK/CCL25 in T lymphocyte-endothelium
      interaction in inflamed and uninflamed intestinal mucosa.
AB  - It has recently been suggested that C-C chemokines may play a role in the organ
      specific homing of lymphocytes, but there is not enough in vivo evidence in
      intestinal mucosa. The aim of this study was to examine whether thymus-expressed
      chemokine (TECK)/CCL25 and its ligand CCR9 are involved in T-lymphocyte
      interaction with microvessels of murine intestinal mucosa. T lymphocytes from the
      small intestine were fluorescence labeled, and their adhesion to mucosal
      microvessels was observed by intravital microscopy. Lamina proprial lymphocytes
      (LPL) and intraepithelial lymphocytes (IEL) adhered to both the small intestine
      and colon, and desensitization of CCR9 with TECK/CCL25 or anti-TECK/CCL25
      antibody significantly inhibited these adhesions only in small intestine. At both
      sites, TNF-alpha significantly increased LPL adhesion but not IEL adhesion.
      Desensitization of CCR9 or anti-TECK/CCL25 antibody also attenuated the TNF-alpha
      induced LPL adhesion in the small intestine. Increased expression of TECK/CCL25
      by TNF-alpha was observed in the lamina propria of small intestine. TECK/CCL25
      may thus play an important role in the adherence of mucosal lymphocytes to the
      microvessels of the small intestine but not the colon under uninflamed as well as
      inflamed conditions.

PMID- 14592944
TI  - Hepcidin regulation of ferroportin 1 expression in the liver and intestine of the
      rat.
AB  - Hepcidin has been implicated as the iron stores regulator: a hepatic signaling
      molecule that regulates intestinal iron absorption by undefined mechanisms. The
      possibility that hepcidin regulates the expression of ferroportin 1 (FPT1), the
      basolateral iron transporter, was examined in rats after administration of LPS,
      an iron chelator, or His-tagged recombinant hepcidin (His-rHepc). In the liver,
      LPS stimulated a biphasic increase of hepcidin mRNA with peaks of mRNA at 6 and
      36 h. Concurrently, hepatic FPT1 mRNA expression decreased to minimal level at 6
      h and then increased with a peak at 24-36 h. LPS also induced biphasic changes in
      intestinal FPT1 mRNA expression, with decreased levels at 6 h and increased
      expression at 48 h. Whereas the initial decrease of FPT1 coincides with an LPS
      induced decrease in serum iron, both intestinal and hepatic FPT1 expression
      recovered, whereas serum iron concentration continued to decrease for at least 24
      h. Dietary iron ingestion increased intestinal ferritin protein production but
      did not reduce intestinal FPT1 mRNA expression. The iron chelator
      pyrrolidinedithiocarbamate (PDTC) stimulated hepatic hepcidin without suppressing
      intestinal FPT1 expression. In PDTC-treated rats, LPS stimulated no additional
      hepatic hepcidin expression but did increase intestinal FPT1 expression.
      Administration of HisrHepc induced significant reduction of intestinal FPT1
      expression. Taken together, these data suggest that hepcidin mediates LPS-induced
      downregulation of intestinal FPT1 expression and that the hepcidin signaling
      pathway involves a PDTC-sensitive step.

PMID- 14592945
TI  - Phosphorylated HSP27 essential for acetylcholine-induced association of RhoA with
      PKCalpha.
AB  - Reorganization of the cytoskeleton and association of contractile proteins are
      important steps in modulating smooth muscle contraction. Heat shock protein (HSP)
      27 has significant effects on actin cytoskeletal reorganization during smooth
      muscle contraction. We investigated the role of phosphorylated HSP27 in
      modulating acetylcholine-induced sustained contraction of smooth muscle cells
      from the rabbit colon by transfecting smooth muscle cells with phosphomimic (3D)
      or nonphosphomimic (3G) HSP27. In 3G cells, the initial peak contractile response
      at 30 s was inhibited by 25% (24.0 +/- 4.5% decrease in cell length, n = 4). The
      sustained contraction was greatly inhibited by 75% [9.3 +/-.9% decreases in cell
      length (n = 4)]. Furthermore, in 3D cells, translocation of both PKCalpha and of
      RhoA was greatly enhanced and resulted in a greater association of PKCalpha-RhoA
      in the membrane fraction. In 3G transfected cells, PKCalpha and RhoA failed to
      translocate in response to stimulation with acetylcholine, resulting in an
      inhibition of association of PKCalpha-RhoA in the membrane fraction. Studies
      using GST-RhoA fusion protein indicate that there is a direct association of RhoA
      with PKCalpha and with HSP27. The results suggest that phosphorylated HSP27 plays
      a crucial role in the maintenance of association of PKCalpha-RhoA in the membrane
      fraction and in the maintenance of acetylcholine-induced sustained contraction.

PMID- 14592946
TI  - Characteristics of intermittent mitochondrial transport in guinea pig enteric
      nerve fibers.
AB  - Enteric neurons controlling various gut functions are prone to oxidative insults
      that might damage mitochondria (e.g., intestinal inflammation). To resume local
      energy supply, mitochondria need to be transported. We used MitoTracker dyes and
      confocal microscopy to investigate basic characteristics of mitochondrial
      transport in guinea pig myenteric neurites. During a 10-s observation of 1 mm
      nerve fiber, on average, three mitochondria were transported at an average speed
      of 0.41 +/- 0.02 microm/s. Movement patterns were clearly erratic, and velocities
      were independent of mitochondrial size. The velocity oscillated periodically (
      approximately 6 s) but was not consistently affected by structures such as en
      route boutons, bifurcations, or stationary mitochondria. Also, mitochondria
      transported in opposite directions did not necessarily affect each others'
      mobility. Transport was blocked by microtubule disruption (100 microM
      colchicine), and destabilization (1 microM cytochalasin-D) or stabilization (10
      microM phalloidin) of actin filaments, respectively, decreased (0.22 +/- 0.02
      microm/s, P < 0.05) or increased (0.53 +/- 0.02 microm/s, P < 0.05) transport
      speed. Transport was inhibited by TTX (1 microM), and removal of extracellular
      Ca(2+) (plus 2 mM EGTA) had no effect. However, depletion of intracellular stores
      (thapsigargin) reduced (to 33%) and slowed the transport significantly (0.18 +/-
      0.02 microm/s, P < 0.05), suggesting an important role for stored Ca(2+) in
      mitochondrial transport. Transport was also reduced (to 21%) by the mitochondrial
      uncoupler FCCP (1 microM) in a time-dependent fashion and slowed by oligomycin
      (10 microM). We conclude that mitochondrial transport is remarkably independent
      of structural nerve fiber properties. We also show that mitochondrial transport
      is TTX sensitive and speeds up by stabilizing actin and that functional Ca(2+)
      stores are required for efficient transport.

PMID- 14592947
TI  - Stomach-brain communication by vagal afferents in response to luminal acid
      backdiffusion, gastrin, and gastric acid secretion.
AB  - Vagal afferents play a role in gut-brain signaling of physiological and
      pathological stimuli. Here, we investigated how backdiffusion of luminal HCl or
      NH(4)OH and pentagastrin-stimulated acid secretion interact in the communication
      between rat stomach and brain stem. Rats were pretreated intraperitoneally with
      vehicle or appropriate doses of cimetidine, omeprazole, pentagastrin,
      dexloxiglumide (CCK(1) receptor antagonist), and itriglumide (CCK(2) receptor
      antagonist) before intragastric administration of saline or backdiffusing
      concentrations of HCl or NH(4)OH. Two hours later, neuronal activation in the
      nucleus of the solitary tract (NTS) and area postrema was visualized by c-Fos
      immunohistochemistry. Exposure of the rat gastric mucosa to HCl (0.15-0.5 M) or
      NH(4)OH (0.1-0.3 M) led to a concentration-dependent expression of c-Fos in the
      NTS, which was not related to gender, gastric mucosal injury, or gastropyloric
      motor alterations. The c-Fos response to HCl was diminished by cimetidine and
      omeprazole, enhanced by pentagastrin, and left unchanged by dexloxiglumide and
      itriglumide. Pentagastrin alone caused an omeprazole-resistant expression of c
      fos, which in the NTS was attenuated by itriglumide and prevented by
      dexloxiglumide but in the area postrema was reduced by dexloxiglumide and
      abolished by itriglumide. We conclude that vagal afferents transmit physiological
      stimuli (gastrin) and pathological events (backdiffusion of luminal HCl or
      NH(4)OH) from the stomach to the brain stem. These communication modalities
      interact because, firstly, acid secretion enhances afferent signaling of gastric
      acid backdiffusion and, secondly, gastrin activates NTS neurons through
      stimulation of CCK(1) receptors on vagal afferents and of CCK(2) receptors on
      area postrema neurons projecting to the NTS.

PMID- 14592948
TI  - IGF-I stimulates human intestinal smooth muscle cell growth by regulation of G1
      phase cell cycle proteins.
AB  - Autocrine production of insulin-like growth factor-I (IGF-I) regulates growth of
      human intestinal muscle cells by activation of distinct phosphatidylinositol 3
      kinase (PI3-kinase)-dependent and ERK1/2-dependent pathways. The aim of the
      present study was to determine the mechanisms by which IGF-I regulates the G(1)
      phase of the cell cycle and muscle cell proliferation. Incubation of quiescent
      cells with IGF-I stimulated time-dependent cell cycle progression measured by
      using fluorescence-activated cell sorting analysis and by incorporation of
      [(3)H]thymidine. Studies using a microarray-based approach were used initially to
      identify genes expressed in human intestinal muscle encoding proteins known to
      participate in the G(1) phase of the cell cycle that were regulated by IGF-I.
      Incubation of muscle cells for 24 h with IGF-I elicited greater than fivefold
      increase in the expression of cyclin D1 and greater than twofold increase in
      retinoblastoma protein (Rb1). IGF-I elicited a time-dependent increase in cyclin
      D1 protein levels mediated jointly by ERK1/2-dependent and PI3-kinase-dependent
      mechanisms. Increase in cyclin D1 levels was accompanied by a time-dependent
      increase in cyclin D1-dependent cyclin-dependent kinase-4 (CDK4) activity. IGF-I
      also elicited a rapid time-dependent increase in Rb-(Ser807/811) phosphorylation,
      the specific target of the cyclin D(1)-dependent CDK4 kinase, and a slower
      increase in total Rb protein levels. We conclude that IGF-I stimulates G(1) phase
      progression, DNA synthesis, and cell proliferation of human intestinal smooth
      muscle cells. Effects of IGF-I on proliferation are mediated jointly by ERK1/2
      dependent and PI3-kinase-dependent pathways that regulate cyclin D1 levels, CDK4
      activity, and Rb activity.

PMID- 14592949
TI  - Possible involvement of ryanodine receptor-mediated intracellular calcium release
      in the effect of corticotropin-releasing factor on adrenocorticotropin secretion.
AB  - We examined the role of intracellular calcium release in the regulation of CRH
      induced ACTH secretion using the AtT20 corticotroph cell line. We found that
      ruthenium red, an inhibitor of ryanodine receptor, substantially diminished the
      secretory response, whereas Xestospongin C, an inositol 1,4,5-triphosphate
      receptor antagonist, had no effect. Expression of two ryanodine receptor subtypes
      (RyR1 and RyR3) was confirmed by RT-PCR. We also found that caffeine, a ryanodine
      receptor agonist, significantly stimulated, whereas thapsigargin, which causes
      depletion of intracellular calcium store, markedly diminished, the ACTH release.
      These results suggest that ryanodine receptor-mediated calcium-induced calcium
      release is involved in the regulation of CRH-induced ACTH release.

PMID- 14592950
TI  - Urocortin II is expressed in human pregnant myometrial cells and regulates myosin
      light chain phosphorylation: potential role of the type-2 corticotropin-releasing
      hormone receptor in the control of myometrial contractility.
AB  - The family of CRH-related peptides are suggested to play important roles in the
      control of myometrial contractility during pregnancy and labor. In this study we
      investigated the expression of urocortin II (UCN II) in human myometrium and its
      ability to phosphorylate intracellular components that can be involved in
      modulating myometrial contractility. Using RT-PCR and fluorescent in situ
      hybridization, we demonstrated that UCN II and type-2 CRH receptor (CRH-R2) mRNAs
      were expressed in human nonpregnant and pregnant myometrium. Immunofluorescent
      studies confirmed protein expression of UCN II in human pregnant myometrial
      cells, whereas chemical cross-linking studies with radiolabeled UCN II confirmed
      the presence of CRH-R2 sites with an apparent molecular mass of 50 kDa. Treatment
      of primary human myometrial cells with UCN II to specifically activate CRH-R2
      resulted in a dose-dependent increase of myosin light chain (MLC(20))
      phosphorylation. Activation of protein kinase C (PKC) and ERK1/2 was required for
      the UCN II-induced activation of MLC(20), because treatment of myometrial cells
      with inhibitors of MAPK kinase 1 (U0126) and PKC (bisindolylmaleimide) inhibited
      the UCN II-induced phosphorylation of MLC(20). Furthermore, the UCN II effect on
      MLC(20) was dependent on RhoA translocation to the membrane and subsequent
      activation of RhoA-associated kinase, as shown by the use of the specific
      inhibitors exoenzyme C3 and Y27632. Collectively, our data suggest a distinctive
      role for CRH-R2- specific agonists like UCN II in the control of myometrial
      contractility during human pregnancy involving sequential activation of PKC, MAPK
      kinase 1, ERK1/2, RhoA, and RhoA-associated kinase, leading to the MLC(20)
      phosphorylation.

PMID- 14592951
TI  - Adiponectin ameliorates dyslipidemia induced by the human immunodeficiency virus
      protease inhibitor ritonavir in mice.
AB  - Although the clinical application of HIV protease inhibitors (PIs) has markedly
      reduced HIV-related morbidity and mortality, it is now recognized that PI-based
      therapy often causes serious metabolic disorders, including hyperlipidemia and
      premature atherosclerosis. The etiology of these adverse effects remains obscure.
      Here, we demonstrate that deficiency of the fat-derived hormone adiponectin might
      play a role. The steady-state mRNA levels of the adiponectin gene and secretion
      of this protein from 3T3-L1 adipocytes are significantly decreased after
      treatment with several PIs (indinavir, nelfinavir, and ritonavir), with ritonavir
      having the greatest effect. Intragastric administration of ritonavir into mice
      decreases plasma concentrations of adiponectin and concurrently increases the
      plasma levels of triglyceride, free fatty acids, and cholesterol. Adiponectin
      replacement therapy markedly ameliorates ritonavir-induced elevations of
      triglyceride and free fatty acids. These beneficial effects of adiponectin are
      partly due to its ability to decrease ritonavir-induced synthesis of fatty acids
      and triglyceride, and to increase fatty acid combustion in the liver tissue. In
      contrast, adiponectin has little effect on ritonavir-induced hypercholesterolemia
      and hepatic cholesterol synthesis. These results suggest that hypoadiponectinemia
      is partly responsible for the metabolic disorders induced by HIV PIs, and
      adiponectin or its agonists might be useful for the treatment of these disorders.

PMID- 14592952
TI  - Glucose sensitivity and metabolism-secretion coupling studied during two-year
      continuous culture in INS-1E insulinoma cells.
AB  - Rat insulinoma-derived INS-1 cells constitute a widely used beta-cell surrogate.
      However, due to their nonclonal nature, INS-1 cells are heterogeneous and are not
      stable over extended culture periods. We have isolated clonal INS-1E cells from
      parental INS-1 based on both their insulin content and their secretory responses
      to glucose. Here we describe the stable differentiated INS-1E beta-cell phenotype
      over 116 passages (no. 27-142) representing a 2.2-yr continuous follow-up. INS-1E
      cells can be safely cultured and used within passages 40-100 with average insulin
      contents of 2.30 +/- 0.11 microg/million cells. Glucose-induced insulin secretion
      was dose-related and similar to rat islet responses. Secretion saturated with a
      6.2-fold increase at 15 mm glucose, showing a 50% effective concentration of 10.4
      mm. Secretory responses to amino acids and sulfonylurea were similar to those of
      islets. Moreover, INS-1E cells retained the amplifying pathway, as judged by
      glucose-evoked augmentation of insulin release in a depolarized state. Regarding
      metabolic parameters, INS-1E cells exhibited glucose dose-dependent elevations of
      NAD(P)H, cytosolic Ca(2+), and mitochondrial Ca(2+) levels. In contrast,
      mitochondrial membrane potential, ATP levels, and cell membrane potential were
      all fully activated by 7.5 mm glucose. Using the perforated patch clamp
      technique, 7.5 and 15 mm glucose elicited electrical activity to a similar
      degree. A K(ATP) current was identified in whole cell voltage clamp using
      diazoxide and tolbutamide. As in native beta-cells, tolbutamide induced
      electrical activity, indicating that the K(ATP)conductance is important in
      setting the resting potential. Therefore, INS-1E cells represent a stable and
      valuable beta-cell model.

PMID- 14592953
TI  - Regulation of oocyte microvilli development in the baboon fetal ovary by
      estrogen.
AB  - We recently showed that the number of primordial follicles was reduced by 50% in
      ovaries of near-term fetal baboons deprived of estrogen in utero and restored to
      normal in animals supplemented with estrogen. Oocytes are avascular and rely on
      surrounding granulosa cells for nutrients, a process facilitated by microvilli on
      the oocyte surface. However, our understanding of oocyte microvillus development
      in the primate fetal ovary is incomplete. Thus, we determined whether estrogen
      regulates formation of oocyte microvilli in utero. Fetal ovaries were obtained on
      d 165 gestation (term = d 184) from baboons untreated (n = 3) or treated on d 100
      165 with aromatase inhibitor CGS 20267 (estrogen suppressed by 95%; n = 5) or CGS
      20267 and estradiol (n = 4). Follicles with intact (homogeneous cytoplasm) or
      nonintact (cytoplasm vacuolated) oocytes were quantified and the number/height of
      oocyte microvilli determined by electron microscopy. In untreated baboons, the
      mean (+/-se) number of follicles/0.08 mm(2) with an intact oocyte (11.5 +/- 0.5)
      was decreased (P < 0.05) by 70% in fetal ovaries of estrogen-suppressed baboons
      (3.4 +/- 0.2) and restored (P < 0.05) by CGS 20267 and estradiol (11.2 +/- 1.2).
      In estrogen-deprived fetuses, the number of microvilli/intact oocyte (23 +/- 3)
      was 56% lower (P < 0.01) than normal (52 +/- 5) and restored by CGS 20267 and
      estrogen (62 +/- 4). Moreover, in intact oocytes of estrogen-suppressed baboons,
      height (nm) of microvilli (105 +/- 11) was 54-62% lower (P < 0.01) than in intact
      oocytes of fetal ovaries of untreated (228 +/- 13) or estrogen-treated (274 +/-
      17) baboons. In estrogen-replete baboons, the number of microvilli in intact
      oocytes was 2-fold greater (P < 0.01) than in nonintact oocytes. However, in
      estrogen-deprived baboons, no microvilli were detected in nonintact oocytes and
      the number of microvilli in intact oocytes was similar to that in nonintact
      oocytes of untreated fetuses. We conclude that development of microvilli in
      oocytes of primordial follicles in the primate fetal ovary is regulated by
      estrogen. Collectively, these results and those of our previous studies indicate
      that estrogen regulates fetal ovarian folliculogenesis and development of
      follicles with oocytes composed of microvilli critical for nutrient uptake and
      presumably long-term survival.

PMID- 14592954
TI  - Regulation of the human cholesterol 7alpha-hydroxylase gene (CYP7A1) by thyroid
      hormone in transgenic mice.
AB  - Thyroid hormones exert significant changes in the metabolism of bile acids.
      However, in humans, the effect of thyroid hormone on cholesterol 7alpha
      hydroxylase (cyp7a), the rate- controlling enzyme in the classical bile acid
      biosynthetic pathway, remains poorly understood and has been difficult to study
      directly in vivo. Previous studies from our laboratory have shown that the
      activity of the human cholesterol 7alpha-hydroxylase gene promoter is repressed
      by T(3) in cultured cells. Accordingly, we hypothesized that T(3) would
      negatively regulate human CYP7A1 gene expression in vivo. We tested this
      hypothesis by inducing hypo- and hyperthyroidism in transgenic mice expressing
      the human CYP7A1 gene. Hypothyroidism did not affect the abundance of human cyp7a
      mRNA in transgenic mice. In hyperthyroid male mice, human cyp7a mRNA abundance
      was decreased. No significant change in cyp7a mRNA abundance was observed in
      hyperthyroid female mice. Gender differences in the amount of cholesterol and
      bile acids in gallbladder bile were also observed. The data indicate that thyroid
      hormone can repress the human CYP7A1 gene in transgenic mice, but this effect is
      dependent on gender in this in vivo model.

PMID- 14592956
TI  - Connective tissue growth factor is up-regulated in the diabetic retina:
      amelioration by angiotensin-converting enzyme inhibition.
AB  - Connective tissue growth factor (CTGF) has been postulated to have prosclerotic
      and angiogenic properties. The aim of this present study was to characterize
      retinal CTGF expression in the absence and presence of diabetes and in the
      context of treatment with the angiotensin-converting enzyme (ACE) inhibitor,
      perindopril. Retinas were obtained from control, diabetic, and diabetic plus
      perindopril-treated (3 mg/d) rats. CTGF gene expression was quantitated by RT-PCR
      and localized by in situ hybridization. CTGF protein expression was analyzed by
      Western blotting and localized by immunohistochemistry. Diabetes was associated
      with a greater than 2-fold increase in CTGF mRNA levels, which was attenuated by
      perindopril treatment. CTGF immunoreactivity was increased almost 2-fold in
      diabetes and was ameliorated by the ACE inhibitor perindopril. By in situ
      hybridization and immunohistochemistry, the major site of CTGF gene expression in
      the retina of diabetic rats was the ganglion cell layer. Based on the known in
      vivo effects of CTGF, it is postulated that this growth factor plays a pivotal
      role in mediating diabetes-associated retinal pathology. Furthermore, the
      protective effects of ACE inhibitors on retinal pathology may partly be mediated
      via effects on retinal CTGF expression.

PMID- 14592955
TI  - Novel action of activin and bone morphogenetic protein in regulating aldosterone
      production by human adrenocortical cells.
AB  - We have uncovered a functional bone morphogenetic protein (BMP) and activin
      system complete with ligands (BMP-6 and activin betaA/betaB), receptors (activin
      receptor-like kinase receptors 2, 3, and 4; activin type-II receptor; and BMP
      type-II receptor), and the binding protein follistatin in the human
      adrenocortical cell line H295R. Administration of activin and BMP-6 to cultures
      of H295R cells caused concentration-responsive increases in aldosterone
      production. The mRNA levels of steroidogenic acute regulatory protein or P450
      steroid side-chain cleavage enzyme, the rate-limiting steps of adrenocortical
      steroidogenesis, were enhanced by activin and BMP-6. Activin and BMP-6 also
      activated the transcription of steroidogenic acute regulatory protein as well as
      the late-step steriodogenic enzyme CYP11B2. Activin enhanced ACTH-, forskolin-,
      or dibutyryl-cAMP- but not angiotensin II (Ang II)-induced aldosterone
      production, whereas BMP-6 specifically augmented Ang II-induced aldosterone
      production. Activin and ACTH but not BMP-6 increased cAMP production.
      Follistatin, which inhibits activin actions by binding, suppressed basal and ACTH
      induced aldosterone secretion but failed to affect the Ang II-induced aldosterone
      level. Furthermore, MAPK signaling appeared to be involved in aldosterone
      production induced by Ang II and BMP-6 because an inhibitor of MAPK activation,
      U0126, reduced the level of aldosterone synthesis stimulated by Ang II and BMP-6
      but not activin. In addition, Ang II reduced the expression levels of BMP-6 but
      increased that of activin betaB, whereas ACTH had no effect on these levels.
      Collectively, the present data suggest that activin acts to regulate adrenal
      aldosterone synthesis predominantly by modulating the ACTH-cAMP-protein kinase A
      signaling cascade, whereas BMP-6 works primarily by modulating the Ang II-MAPK
      cascade in human adrenal cortex in an autocrine/paracrine fashion.

PMID- 14592957
TI  - Estrogen regulation of neurokinin B gene expression in the mouse arcuate nucleus
      is mediated by estrogen receptor alpha.
AB  - Neurokinin B (NKB) gene expression is elevated in the infundibular (arcuate)
      nucleus of the hypothalamus in postmenopausal women. Estrogen replacement
      decreases both the number of NKB mRNA-expressing neurons and the level of
      expression within individual cells. Similarly, NKB gene expression is elevated in
      ovariectomized rats and reduced after estrogen treatment. The actions of estrogen
      in the brain can be mediated via either estrogen receptor alpha (ERalpha) or
      estrogen receptor beta (ERbeta). In the rodent arcuate nucleus (ARC), more
      ERalpha- than ERbeta-containing cells are present, suggesting that ERalpha might
      be directly responsible for estrogen regulation of NKB gene expression. However,
      an indirect effect via ERbeta could not be ruled out. Here we used ERalpha
      knockout and ERbeta knockout mice to identify the type of ER responsible for
      mediating estrogen action on NKB gene expression in the ARC. Using in situ
      hybridization histochemistry, we have found that estrogen treatment significantly
      reduced NKB gene expression in the ARC of ovariectomized ERbeta knockout mice,
      but had no effect on NKB mRNA levels in ERalpha knockout mice. These data
      indicate that ERalpha mediates the increase in NKB gene expression associated
      with ovariectomy in rodents and might also be responsible for the increase in NKB
      in postmenopausal women.

PMID- 14592958
TI  - The promoter of the rat gonadotropin-releasing hormone receptor gene directs the
      expression of the human placental alkaline phosphatase reporter gene in
      gonadotrope cells in the anterior pituitary gland as well as in multiple
      extrapituitary tissues.
AB  - Previous studies dealing with the mechanisms underlying the tissue-specific and
      regulated expression of the GnRH receptor (GnRH-R) gene led us to define several
      cis-acting regulatory sequences in the rat GnRH-R gene promoter. These include
      functional sites for steroidogenic factor 1, activator protein 1, and motifs
      related to GATA and LIM homeodomain response elements as demonstrated primarily
      in transient transfection assays in mouse gonadotrope-derived cell lines. To
      understand these mechanisms in more depth, we generated transgenic mice bearing
      the 3.3-kb rat GnRH-R promoter linked to the human placental alkaline phosphatase
      reporter gene. Here we show that the rat GnRH-R promoter drives the expression of
      the reporter gene in pituitary cells expressing the LHbeta and/or FSHbeta subunit
      but not in TSHbeta- or GH-positive cells. Furthermore, the spatial and temporal
      pattern of the transgene expression during the development of the pituitary was
      compatible with that characterizing the emergence of the gonadotrope lineage. In
      particular, transgene expression is colocalized with the expression of the
      glycoprotein hormone alpha-subunit at embryonic day 13.5 and with that of
      steroidogenic factor 1 at later stages of pituitary development. Transgene
      expression was also found in specific brain areas, such as the lateral septum and
      the hippocampus. A single promoter is thus capable of directing transcription in
      highly diverse tissues, raising the question of the different combinations of
      transcription factors that lead to such a multiple, but nevertheless cell
      specific, expressions of the GnRH-R gene.

PMID- 14592960
TI  - Insulin-like growth factor I increases rat peptide YY promoter activity through
      Sp1 binding sites.
AB  - Studies in rodents demonstrate that the mitogen, IGF-I, stimulates intestinal
      peptide YY (PYY) expression. To investigate whether the stimulatory influence of
      IGF-I is exerted at the level of gene transcription, rat PYY 5'-upstream
      sequences (-2800/+37 bp, -770/+37 bp, -127/+37 bp) fused to the firefly
      luciferase (luc) reporter gene were transfected into rat pheochromocytoma cells
      (PC12) and luc activity measured after IGF-I treatment. IGF-I increased
      transcriptional activity of all constructs similarly; the PYY (-127/+37 bp)-luc
      construct was used in subsequent experiments. IGF-I increased PYY (-127/+37 bp)
      luc activity in a time- and dose-dependent fashion. Sequence analysis detected
      five putative Sp1 binding sites in the -127/+37-bp sequence. EMSA and supershift
      experiments using two oligonucleotide fragments of the -127/+37 region showed
      that Sp1 and Sp3 proteins bound to putative Sp1 sites. Overexpression of Sp1
      greatly increased PYY (-127/+37 bp)-luc activity and site-directed mutagenesis of
      putative Sp1 binding sites decreased basal and IGF-I-induced elevations in PYY (
      127/+37 bp)-luc activity. IGF-I treatment also increased Sp1 protein levels and
      binding activity. Blockade of the IGF-I receptor (IGF-IR) with an IGF-IR antibody
      decreased the stimulatory influence of IGF-I on Sp1 protein levels and PYY (
      127/+37 bp)-luc activity. Together, these findings indicate that IGF-I functions
      as a positive regulator of PYY gene expression and that the stimulatory effect
      may be mediated by Sp1 proteins that bind to the proximal PYY promoter region.

PMID- 14592959
TI  - Androgen contributes to gender-related cardiac hypertrophy and fibrosis in mice
      lacking the gene encoding guanylyl cyclase-A.
AB  - Myocardial hypertrophy and extended cardiac fibrosis are independent risk factors
      for congestive heart failure and sudden cardiac death. Before age 50, men are at
      greater risk for cardiovascular disease than age-matched women. In the current
      studies, we found that cardiac hypertrophy and fibrosis were significantly more
      pronounced in males compared with females of guanylyl cyclase-A knockout (GC-A
      KO) mice at 16 wk of age. These gender-related differences were not seen in wild
      type mice. In the further studies, either castration (at 10 wk of age) or
      flutamide, an androgen receptor antagonist, markedly attenuated cardiac
      hypertrophy and fibrosis in male GC-A KO mice without blood pressure change. In
      contrast, ovariectomy (at 10 wk of age) had little effect. Also, chronic
      testosterone infusion increased cardiac mass and fibrosis in ovariectomized GC-A
      mice. None of the treatments affected cardiac mass or the extent of fibrosis in
      wild-type mice. Overexpression of mRNAs encoding atrial natriuretic peptide,
      brain natriuretic peptide, collagens I and III, TGF-beta1, TGF-beta3,
      angiotensinogen, and angiotensin converting enzyme in the ventricles of male GC-A
      KO mice was substantially decreased by castration. The gender differences were
      virtually abolished by targeted deletion of the angiotensin II type 1A receptor
      gene (AT1A). Neither castration nor testosterone administration induced any
      change in the cardiac phenotypes of double-KO mice for GC-A and AT1A. Thus, we
      suggest that androgens contribute to gender-related differences in cardiac
      hypertrophy and fibrosis by a mechanism involving AT1A receptors and GC-A.

PMID- 14592961
TI  - Development of a murine model of autoimmune thyroiditis induced with homologous
      mouse thyroid peroxidase.
AB  - Autoimmune thyroid disease (AITD) is a common autoimmune disease. Thyroid
      peroxidase (TPO) is a well characterized autoantigen in AITD. Autoantibodies and
      autoreactive T lymphocytes to TPO are believed to play a major role in the
      pathogenesis of lymphocytic thyroiditis. To understand the pathogenic mechanisms
      of AITD and the role of TPO, we have established a mouse model of lymphocytic
      thyroiditis by immunizing C57Bl/6 (H-2(b)), CBA (H-2(k)), and C57Bl/6 x CBA F1
      mice with recombinant murine TPO (rmTPO) ectodomain comprising amino acid residue
      1-837 produced in Escherichia coli. Mice were immunized with 30 microg purified
      ectodomain in complete Freund's adjuvant. Antibodies against rmTPO were detected
      in the serum of all mice from day 21 onward. Draining lymph node cells from rmTPO
      immunized animals showed dose-dependent proliferation to TPO stimulation. Mice
      killed at d 50 and 90 revealed variable degrees of thyroiditis with infiltration
      of mononuclear cells and destruction of thyroid follicles. C57Bl/6 and the F1
      mice, in comparison with CBA mice, showed a greater degree of thyroiditis. There
      was a lack of correction between the intensity of thyroiditis and the anti-TPO
      response. Immunotyping of the thyroid cellular infiltrates showed predominantly
      CD4+ T cells and B220+ B cells but scanty CD8+ T cells. None of the control mice
      injected with the purified fusion partner developed anti-TPO antibodies and
      thyroiditis. In conclusion, a genuine autoimmune mouse model of lymphocytic
      thyroiditis was established using autologous mouse TPO. This new model induced
      with autologous TPO will lead to a better understanding of the mechanisms in
      destructive thyroiditis and will assist in the development of new strategies for
      modulating the pathogenic immune response.

PMID- 14592962
TI  - Galanin receptor subtype GalR2 mediates apoptosis in SH-SY5Y neuroblastoma cells.
AB  - Recently we have shown that galanin binding significantly correlates with
      survival in neuroblastoma patients, indicating a possible modulatory role of
      galanin receptors in neuroblastic tumor biology. However, the molecular
      mechanisms beyond this correlation have not been elucidated. Here, the cellular
      effects on activation of specific galanin receptor subtypes in human SH-SY5Y
      neuroblastoma cells were analyzed using a tetracycline-controlled expression
      system. Pharmacological studies confirmed the inducible expression of high
      affinity binding sites for galanin in SH-SY5Y cells transfected with the galanin
      receptors GalR1 (SY5Y/GalR1) and GalR2 (SY5Y/GalR2). Microphysiometry revealed
      that both receptor subtypes were able to mediate an intracellular signal upon
      galanin application. Interestingly, induction of receptor expression and
      treatment with 100 nm galanin resulted in a dramatic decrease in cell viability
      in SY5Y/GalR2 cells (93 +/- 3%) compared with a less pronounced effect in
      SY5Y/GalR1 cells (19 +/- 10%). The antiproliferative potency of galanin was 100
      fold higher in SY5Y/GalR2 (50% effective concentration, 1.1 nm) than in
      SY5Y/GalR1 cells (50% effective concentration, 190 nm). Furthermore, activation
      of receptor expression and exposure to galanin resulted in apparent morphological
      changes indicative of apoptosis in SY5Y/GalR2 cells only. Induction of cell death
      by the apoptotic process was confirmed by poly-(ADP-ribose)-polymerase cleavage,
      caspase-3 activation, and the typical laddering of DNA. This study indicates that
      a high level of GalR2 expression is able to inhibit cell proliferation and induce
      apoptosis in neuroblastoma cells and therefore identifies GalR2 as a possible
      target for pharmacological intervention in neuroblastoma.

PMID- 14592963
TI  - Agouti-related protein antagonizes glucocorticoid production induced through
      melanocortin 4 receptor activation in bovine adrenal cells: a possible autocrine
      control.
AB  - Agouti-related protein (Agrp), primarily expressed in the hypothalamus, is an
      endogenous antagonist of alphaMSH at the level of melanocortin 3 receptor (MC3-R)
      and MC4-R, but the adrenal gland represents the second major Agrp-expressing
      tissue. In adrenal fasciculata cells, the glucocorticoid secretion is under the
      control of ACTH, which binds specifically MC2-R, the only functional melanocortin
      receptor described in these cells to date. Nevertheless, using cultured bovine
      fasciculata adrenal cells, we report that Agrp has no antagonistic properties
      against ACTH at the level of MC2-R. In our studies, (Nle4, d-Phe7)-alphaMSH (NDP
      alphaMSH) stimulated the production of cortisol in a dose-dependent manner, and
      these effects were abolished by Agrp or SHU9119, a synthetic antagonist of MC3-R
      and MC4-R. Using a more specific antagonist (JKC-363) and RT-PCR analysis, we can
      postulate that the effects of NDP-alphaMSH were mediated via MC4-R. These results
      are suggestive that adrenal glucocorticoid production could be regulated through
      MC4-R that may have some relevance in the physiology of adrenal cells. Moreover,
      Agrp might exert an autocrine control on adrenal cells because a protein with
      biological Agrp-like activity is secreted by these cells. This peptide could then
      modulate locally the functions of some peripheral tissues such as adrenals.

PMID- 14592964
TI  - Leptin modulates behavioral responses to sweet substances by influencing
      peripheral taste structures.
AB  - Leptin is a hormone that regulates body weight homeostasis mainly via the
      hypothalamic functional leptin receptor Ob-Rb. Recently, we proposed that the
      taste organ is a new peripheral target for leptin. Leptin selectively inhibits
      mouse taste cell responses to sweet substances and thereby may act as a sweet
      taste modulator. The present study further investigated leptin action on the
      taste system by examining expression of Ob-Rb in taste cells and behavioral
      responses to sweet substances in leptin-deficient ob/ob, and Ob-Rb-deficient
      db/db mice and their normal litter mates. RT-PCR analysis showed that Ob-Rb was
      expressed in taste cells in all strains tested. The db/db mice, however, had a RT
      PCR product containing an abnormal db insertion that leads to an impaired shorter
      intracellular domain. In situ hybridization analysis showed that the
      hybridization signals for normal Ob-Rb mRNA were detected in taste cells in lean
      and ob/ob mice but not in db/db mice. Two different behavioral tests, one using
      sweet-bitter mixtures as taste stimuli and the other a conditioned taste aversion
      paradigm, demonstrated that responses to sucrose and saccharin were significantly
      decreased after ip injection of leptin in ob/ob and normal littermates, but not
      in db/db mice. These results suggest that leptin suppresses behavioral responses
      to sweet substances through its action on Ob-Rb in taste cells. Such taste
      modulation by leptin may be involved in regulation for food intake.

PMID- 14592965
TI  - Members of the NF90/NFAR protein group are involved in the life cycle of a
      positive-strand RNA virus.
AB  - A major issue of current virology concerns the characterization of cellular
      proteins that operate as functional components of the viral multiplication
      process. Here we describe a group of host factors designated as 'NFAR proteins'
      that are recruited by the replication machinery of bovine viral diarrhea virus, a
      close relative of the human pathogen hepatitis C virus. The NFAR proteins
      associate specifically with both the termini of the viral RNA genome involving
      regulatory elements in the 5' and 3' non-translated regions. Modification of the
      protein interaction sites in the 3' non-translated region yielded viral RNAs that
      were replication deficient. Viral replication was also inhibited by RNAi
      approaches that reduced the concentration of RNA helicase A, a member of the NFAR
      group, in the host cell's cytoplasm. Further experimental data suggest that NFAR
      proteins mediate a circular conformation of the viral genome that may be
      important for the coordination of translation and replication. Because NFAR
      proteins are presumed components of the antiviral response, we suspect that viral
      recruitment may also serve to weaken cellular defense mechanisms.

PMID- 14592966
TI  - Nogo-A at CNS paranodes is a ligand of Caspr: possible regulation of K(+) channel
      localization.
AB  - We report Nogo-A as an oligodendroglial component congregating and interacting
      with the Caspr-F3 complex at paranodes. However, its receptor Nogo-66 receptor
      (NgR) does not segregate to specific axonal domains. CHO cells cotransfected with
      Caspr and F3, but not with F3 alone, bound specifically to substrates coated with
      Nogo-66 peptide and GST-Nogo-66. Binding persisted even after
      phosphatidylinositol- specific phospholipase C (PI-PLC) removal of GPI-linked F3
      from the cell surface, suggesting a direct interaction between Nogo-66 and Caspr.
      Both Nogo-A and Caspr co-immunoprecipitated with Kv1.1 and Kv1.2, and the
      developmental expression pattern of both paralleled compared with Kv1.1,
      implicating a transient interaction between Nogo-A-Caspr and K(+) channels at
      early stages of myelination. In pathological models that display paranodal
      junctional defects (EAE rats, and Shiverer and CGT(-/-) mice), distances between
      the paired labeling of K(+) channels were shortened significantly and their
      localization shifted toward paranodes, while paranodal Nogo-A congregation was
      markedly reduced. Our results demonstrate that Nogo-A interacts in trans with
      axonal Caspr at CNS paranodes, an interaction that may have a role in modulating
      axon-glial junction architecture and possibly K(+)-channel localization during
      development.

PMID- 14592967
TI  - Cytosolic HSP90 associates with and modulates the Arabidopsis RPM1 disease
      resistance protein.
AB  - The Arabidopsis protein RPM1 activates disease resistance in response to
      Pseudomonas syringae proteins targeted to the inside of the host cell via the
      bacterial type III delivery system. We demonstrate that specific mutations in the
      ATP-binding domain of a single Arabidopsis cytosolic HSP90 isoform compromise
      RPM1 function. These mutations do not affect the function of related disease
      resistance proteins. RPM1 associates with HSP90 in plant cells. The Arabidopsis
      proteins RAR1 and SGT1 are required for the action of many R proteins, and
      display some structural similarity to HSP90 co-chaperones. Each associates with
      HSP90 in plant cells. Our data suggest that (i) RPM1 is an HSP90 client protein;
      and (ii) RAR1 and SGT1 may function independently as HSP90 cofactors. Dynamic
      interactions among these proteins can regulate RPM1 stability and function,
      perhaps similarly to the formation and regulation of animal steroid receptor
      complexes.

PMID- 14592968
TI  - High throughput virus-induced gene silencing implicates heat shock protein 90 in
      plant disease resistance.
AB  - Virus-induced gene silencing was used to assess the function of random Nicotiana
      benthamiana cDNAs in disease resistance. Out of 4992 cDNAs tested from a
      normalized library, there were 79 that suppressed a hypersensitive response (HR)
      associated with Pto-mediated resistance against Pseudomonas syringae. However,
      only six of these clones blocked the Pto-mediated suppression of P.syringae
      growth. The three clones giving the strongest loss of Pto resistance had inserts
      corresponding to HSP90 and also caused loss of Rx-mediated resistance against
      potato virus X and N-mediated tobacco mosaic virus resistance. The role of HSP90
      as a cofactor of disease resistance is associated with stabilization of Rx
      protein levels and could be accounted for in part by SGT1 and other cofactors of
      disease resistance acting as co-chaperones. This approach illustrates the
      potential benefits and limitations of RNA silencing in forward screens of gene
      function in plants.

PMID- 14592969
TI  - VE-statin, an endothelial repressor of smooth muscle cell migration.
AB  - The recruitment and proliferation of smooth muscle cells and pericytes are two
      key events for the stabilization of newly formed capillaries during angiogenesis
      and, when out of control in the adult, are the main causes of arteriosclerosis.
      We have identified a novel gene, named VE-statin for vascular endothelial-statin,
      which is expressed specifically by endothelial cells of the developing mouse
      embryo and in the adult, and in early endothelial progenitors. The mouse and
      human VE-statin genes have been located on chromosome 2 and 9, respectively, they
      span >10 kbp and are transcribed in two major variants arising from independent
      initiation sites. The VE-statin transcripts code for a unique protein of 30 kDa
      that contains a signal peptide and two epidermal growth factor (EGF)-like
      modules. VE-statin is found in the cellular endoplasmic reticulum and secreted in
      the cell supernatant. Secreted VE-statin inhibits platelet-derived growth factor
      (PDGF)-BB-induced smooth muscle cell migration, but has no effects on endothelial
      cell migration. VE-statin is the first identified inhibitor of mural cell
      migration specifically produced by endothelial cells.

PMID- 14592970
TI  - Rab5-mediated endosome-endosome fusion regulates hemoglobin endocytosis in
      Leishmania donovani.
AB  - To understand the trafficking of endocytosed hemoglobin (Hb) in Leishmania, we
      investigated the characteristics of in vitro fusion between endosomes containing
      biotinylated Hb (BHb) and avidin-horseradish peroxidase (AHRP). We showed that
      early endosome fusion in Leishmania is temperature and cytosol dependent and is
      inhibited by ATP depletion, ATPgammaS, GTPgammaS and N-ethylmaleimide treatment.
      The Rab5 homolog from Leishmania donovani, LdRab5, was cloned and expressed. Our
      results showed that homotypic fusion between the early endosomes in Leishmania is
      Rab5 dependent. Early endosomes containing BHb fused efficiently with late
      endosomes in a process regulated by Rab7, whereas no fusion between early and
      late endosomes was detected using fluid phase markers. Pre-treatment of early
      endosomes containing BHb with monoclonal antibody specific for the C-terminus of
      the Hb receptor (HbR) or the addition of the C-terminal cytoplasmic fragment of
      the HbR specifically inhibited the fusion with late endosomes, suggesting that
      signal(s) mediated through the HbR cytoplasmic tail promotes the fusion of early
      endosomes containing Hb with late endosomes.

PMID- 14592971
TI  - E-cadherin controls adherens junctions in the epidermis and the renewal of hair
      follicles.
AB  - E-cadherin is thought to mediate intercellular adhesion in the mammalian
      epidermis and in hair follicles as the adhesive component of adherens junctions.
      We have tested this role of E-cadherin directly by conditional gene ablation in
      the mouse. We show that postnatal loss of E-cadherin in keratinocytes leads to a
      loss of adherens junctions and altered epidermal differentiation without
      accompanying signs of inflammation. Overall tissue integrity and desmosomal
      structures were maintained, but skin hair follicles were progressively lost.
      Tumors were not observed and beta-catenin levels were not strongly altered in the
      mutant skin. We conclude that E-cadherin is required for maintaining the adhesive
      properties of adherens junctions in keratinocytes and proper skin
      differentiation. Furthermore, continuous hair follicle cycling is dependent on E
      cadherin.

PMID- 14592972
TI  - PP1 control of M phase entry exerted through 14-3-3-regulated Cdc25
      dephosphorylation.
AB  - It has been known for over a decade that inhibition of protein phosphatase 1
      (PP1) activity prevents entry into M phase, but the relevant substrate has not
      been identified. We report here that PP1 is required for dephosphorylation of the
      Cdc2-directed phosphatase Cdc25 at Ser287 (of Xenopus Cdc25; Ser216 of human
      Cdc25C), a site that suppresses Cdc25 during interphase. Moreover, PP1 recognizes
      Cdc25 directly by interacting with a PP1-binding motif in the Cdc25 N-terminus.
      We have also found that 14-3-3 binding to phospho-Ser287 protects Cdc25 from
      premature dephosphorylation. Upon entry into M phase, 14-3-3 removal from Cdc25
      precedes Ser287 dephosphorylation, suggesting the existence of a phosphatase-
      independent pathway for 14-3-3 removal from Cdc25. We show here that this
      dissociation of 14-3-3 from Cdc25 requires the activity of the cyclin-dependent
      kinase Cdk2, providing a molecular explanation for the previously reported
      requirement for Cdk2 in promoting mitotic entry. Collectively, our data clarify
      several steps important for Cdc25 activation and provide new insight into the
      role of PP1 in Cdc2 activation and mitotic entry.

PMID- 14592973
TI  - Xp38gamma/SAPK3 promotes meiotic G(2)/M transition in Xenopus oocytes and
      activates Cdc25C.
AB  - We have studied the role of p38 mitogen-activated protein kinases (MAPKs) in the
      meiotic maturation of Xenopus oocytes. Overexpression of a constitutively active
      mutant of the p38 activator MKK6 accelerates progesterone-induced maturation.
      Immunoprecipit ation experiments indicate that p38gamma/SAPK3 is the major p38
      activated by MKK6 in the oocytes. We have cloned Xenopus p38gamma (Xp38gamma) and
      show that co-expression of active MKK6 with Xp38gamma induces oocyte maturation
      in the absence of progesterone. The maturation induced by Xp38gamma requires
      neither protein synthesis nor activation of the p42 MAPK-p90Rsk pathway, but it
      is blocked by cAMP-dependent protein kinase. A role for the endogenous Xp38gamma
      in progesterone-induced maturation is supported by the inhibitory effect of
      kinase-dead mutants of MKK6 and Xp38gamma. Furthermore, MKK6 can rescue the
      inhibition of oocyte maturation by anthrax lethal factor, a protease that
      inactivates MAPK kinases. We also show that Xp38gamma can activate the
      phosphatase XCdc25C, and we identified Ser205 of XCdc25C as a major
      phosphorylation site for Xp38gamma. Our results indicate that phosphorylation of
      XCdc25C by Xp38gamma/SAPK3 is important for the meiotic G(2)/M progression of
      Xenopus oocytes.

PMID- 14592974
TI  - The crystal structure of the human polo-like kinase-1 polo box domain and its
      phospho-peptide complex.
AB  - Human polo-like kinase Plk1 localizes to the centrosomes, kinetochores and
      central spindle structures during mitosis. It plays an essential role in
      promoting mitosis and cytokinesis through phosphorylation of a number of
      different substrates. Kinase activity is regulated by a conserved C-terminal
      domain, termed the polo box domain (PBD), which acts both as an autoinhibitory
      domain and as a subcellular localization domain. We have determined the crystal
      structure of Plk1 PBD (residues 367-603) to 2.2 A resolution and the structure of
      a phospho-peptide-PBD (residues 345-603) complex to 2.3 A resolution. The two
      polo boxes of the PBD exhibit identical folds based on a six-stranded beta-sheet
      and an alpha-helix, despite only 12% sequence identity. The phospho-peptide binds
      at a site between the two polo boxes. It makes a short antiparallel beta-sheet
      connection and critical contacts to residues Trp414, Leu490, His538 and Lys540.
      Most of these residues had been shown to be important for biological activity
      through mutational studies. The results provide an explanation for phospho
      peptide recognition and create the basis for new functional studies.

PMID- 14592975
TI  - scribble mutants cooperate with oncogenic Ras or Notch to cause neoplastic
      overgrowth in Drosophila.
AB  - Cancer is a multistep process involving cooperation between oncogenic or tumor
      suppressor mutations and interactions between the tumor and surrounding normal
      tissue. Here we present the first description of cooperative tumorigenesis in
      Drosophila, by using a system that mimics the development of tumors in mammals.
      We have used the MARCM system to generate mutant clones of the apical-basal cell
      polarity tumor suppressor gene, scribble, in the context of normal tissue. We
      show that scribble mutant clones in the eye disc exhibit ectopic expression of
      cyclin E and ectopic cell cycles, but do not overgrow due to increased cell death
      mediated by the JNK pathway and the surrounding wild-type tissue. In contrast,
      when oncogenic Ras or Notch is expressed within the scribble mutant clones, cell
      death is prevented and neoplastic tumors develop. This demonstrates, for the
      first time in Drosophila, that activated alleles of Ras and Notch can act as
      cooperating oncogenes in the development of epithelial tumors, and highlights the
      importance of epithelial polarity regulators in restraining oncogenes and
      preventing tumor formation.

PMID- 14592977
TI  - Feedback control of the protein kinase TAK1 by SAPK2a/p38alpha.
AB  - TAB1, a subunit of the kinase TAK1, was phosphorylated by SAPK2a/p38alpha at
      Ser423, Thr431 and Ser438 in vitro. TAB1 became phosphorylated at all three sites
      when cells were exposed to cellular stresses, or stimulated with tumour necrosis
      factor-alpha (TNF-alpha), interleukin-1 (IL-1) or lipopolysaccharide (LPS). The
      phosphorylation of Ser423 and Thr431 was prevented if cells were pre-incubated
      with SB 203580, while the phosphorylation of Ser438 was partially inhibited by PD
      184352. Ser423 is the first residue phosphorylated by SAPK2a/p38alpha that is not
      followed by proline. The activation of TAK1 was enhanced by SB 203580 in LPS
      stimulated macrophages, and by proinflammatory cytokines or osmotic shock in
      epithelial KB cells or embryonic fibroblasts. The activation of TAK1 by TNF
      alpha, IL-1 or osmotic shock was also enhanced in embryonic fibroblasts from
      SAPK2a/p38alpha-deficient mice, while incubation of these cells with SB 203580
      had no effect. Our results suggest that TAB1 participates in a SAPK2a/p38alpha
      mediated feedback control of TAK1, which not only limits the activation of
      SAPK2a/p38alpha but synchronizes its activity with other signalling pathways that
      lie downstream of TAK1 (JNK and IKK).

PMID- 14592976
TI  - Notch-induced E2A ubiquitination and degradation are controlled by MAP kinase
      activities.
AB  - Notch signals are important for lymphocyte development but downstream events that
      follow Notch signaling are not well understood. Here, we report that signaling
      through Notch modulates the turnover of E2A proteins including E12 and E47, which
      are basic helix-loop-helix proteins crucial for B and T lymphocyte development.
      Notch-induced degradation requires phosphorylation of E47 by p42/p44 MAP kinases.
      Expression of the intracellular domain of Notch1 (N1-IC) enhances the association
      of E47 with the SCF(Skp2) E3 ubiquitin ligase and ubiquitination of E47, followed
      by proteasome-mediated degradation. Furthermore, N1-IC induces E2A degradation in
      B and T cells in the presence of activated MAP kinases. Activation of endogenous
      Notch receptors by treatment of splenocytes with anti-IgM or anti-CD3 plus anti
      CD28 also leads to E2A degradation, which is blocked by the inhibitors of Notch
      activation or proteasome function. Notch-induced E2A degradation depends on the
      function of its downstream effector, RBP-Jkappa, probably to activate target
      genes involved in the ubiquitination of E2A proteins. Thus we propose that Notch
      regulates lymphocyte differentiation by controlling E2A protein turnover.

PMID- 14592978
TI  - C/EBPbeta: a major PML-RARA-responsive gene in retinoic acid-induced
      differentiation of APL cells.
AB  - In acute promyelocytic leukemia (APL), the translocation t(15;17) induces a block
      at the promyelocytic stage of differentiation in an all-trans-retinoic acid
      (ATRA)-responsive manner. Here we report that upon treatment with ATRA, t(15;17)
      cells (NB4) reveal a very rapid increase in protein level and binding activity of
      C/EBPbeta, a C/EBP family member, which was not observed in an ATRA-resistant NB4
      cell line. We further provide evidence that ATRA mediates a direct increase of
      C/EBPbeta, only in PML-RARA (promyelocytic leukemia-retinoic acid receptor alpha)
      expressing cells. In addition, transactivation experiments indicate that the PML
      RARA fusion protein, but not PML-RARA mutants defective in transactivation,
      strongly transactivates the C/EBPbeta promoter. These results suggest that PML
      RARA mediates ATRA-induced C/EBPbeta expression. Finally, we demonstrate the
      importance of C/EBPbeta in granulocytic differentiation. We show that not only
      does C/EBPbeta induce granulocytic differentiation of non-APL myeloid cell lines
      independent of addition of ATRA or other cytokines, but also that C/EBPbeta
      induction is required during ATRA-induced differentiation of APL cells. Taken
      together, C/EBPbeta is an ATRA-dependent PML-RARA target gene involved in ATRA
      induced differentiation of APL cells.

PMID- 14592979
TI  - PKA and MAPK phosphorylation of Prf1 allows promoter discrimination in Ustilago
      maydis.
AB  - Mating in Ustilago maydis requires cross-talk between cAMP and mitogen-activated
      protein kinase (MAPK) signalling. During this process, pheromone response factor
      1 (Prf1) activates transcription of a and b mating type genes by binding to
      pheromone response elements (PREs) located in regulatory regions of these genes.
      Here, we show that PREs are also necessary and sufficient to mediate cAMP-induced
      gene expression. Prf1 interacts with cAMP-dependent protein kinase A (PKA) Adr1
      as well as MAPK Kpp2 in vivo, and its central phosphorylation sites that are
      functionally important are modified by the respective kinases in vitro. PKA sites
      in Prf1 are essential for induced expression of a and b mating type genes. In
      contrast, MAPK sites are not required for pheromone-induced expression of a genes
      but are crucial for pheromone-responsive b gene expression. This illustrates how
      a single transcription factor can integrate signals from two pathways and how its
      phosphorylation status can determine different transcriptional responses.

PMID- 14592980
TI  - Structure of the heterodimeric ecdysone receptor DNA-binding complex.
AB  - Ecdysteroids initiate molting and metamorphosis in insects via a heterodimeric
      receptor consisting of the ecdysone receptor (EcR) and ultraspiracle (USP). The
      EcR-USP heterodimer preferentially mediates transcription through highly
      degenerate pseudo-palindromic response elements, resembling inverted repeats of
      5'-AGGTCA-3' separated by 1 bp (IR-1). The requirement for a heterodimeric
      arrangement of EcR-USP subunits to bind to a symmetric DNA is unusual within the
      nuclear receptor superfamily. We describe the 2.24 A structure of the EcR-USP DNA
      binding domain (DBD) heterodimer bound to an idealized IR-1 element. EcR and USP
      use similar surfaces, and rely on the deformed minor groove of the DNA to
      establish protein-protein contacts. As retinoid X receptor (RXR) is the mammalian
      homolog of USP, we also solved the 2.60 A crystal structure of the EcR-RXR DBD
      heterodimer on IR-1 and found the dimerization and DNA-binding interfaces to be
      the same as in the EcR-USP complex. Sequence alignments indicate that the EcR-RXR
      heterodimer is an important model for understanding how the FXR-RXR heterodimer
      binds to IR-1 sites.

PMID- 14592981
TI  - TFIIIB is phosphorylated, disrupted and selectively released from tRNA promoters
      during mitosis in vivo.
AB  - Mitosis involves a generalized repression of gene expression. In the case of RNA
      polymerase III transcription, this is due to phosphorylation-mediated
      inactivation of TFIIIB, an essential complex comprising the TATA-binding protein
      TBP and the TAF subunits Brf1 and Bdp1. In HeLa cells, this repression is
      mediated by a mitotic kinase other than cdc2-cyclin B and is antagonized by
      protein phosphatase 2A. Brf1 is hyperphosphorylated in metaphase-arrested cells,
      but remains associated with promoters in condensed chromosomes, along with TBP.
      In contrast, Bdp1 is selectively released. Repression can be reversed by raising
      the concentration of Brf1 or Bdp1. The data support a model in which
      hyperphosphorylation disrupts TFIIIB during mitosis, compromising its ability to
      support transcription.

PMID- 14592982
TI  - A chromosomal SIR2 homologue with both histone NAD-dependent ADP
      ribosyltransferase and deacetylase activities is involved in DNA repair in
      Trypanosoma brucei.
AB  - SIR2-like proteins have been implicated in a wide range of cellular events
      including chromosome silencing, chromosome segregation, DNA recombination and the
      determination of life span. We report here the molecular and functional
      characterization of a SIR2-related protein from the protozoan parasite
      Trypanosoma brucei, which we termed TbSIR2RP1. This protein is a chromosome
      associated NAD-dependent enzyme which, in contrast to other known proteins of
      this family, catalyses both ADP-ribosylation and deacetylation of histones,
      particulary H2A and H2B. Under- or overexpression of TbSIR2RP1 decreased or
      increased, respectively, cellular resistance to DNA damage. Treatment of
      trypanosomal nuclei with a DNA alkylating agent resulted in a significant
      increase in the level of histone ADP-ribosylation and a concomitant increase in
      chromatin sensitivity to micrococcal nuclease. Both of these responses correlated
      with the level of TbSIR2RP1 expression. We propose that histone modification by
      TbSIR2RP1 is involved in DNA repair.

PMID- 14592983
TI  - An essential role of DmRad51/SpnA in DNA repair and meiotic checkpoint control.
AB  - Rad51 is a conserved protein essential for recombinational repair of double
      stranded DNA breaks (DSBs) in somatic cells and during meiosis in germ cells.
      Yeast Rad51 mutants are viable but show meiosis defects. In the mouse, RAD51
      deletions cause early embryonic death, suggesting that in higher eukaryotes Rad51
      is required for viability. Here we report the identification of SpnA as the
      Drosophila Rad51 gene, whose sequence among the five known Drosophila Rad51-like
      genes is most closely related to the Rad51 homologs of human and yeast.
      DmRad51/spnA null mutants are viable but oogenesis is disrupted by the activation
      of a meiotic recombination checkpoint. We show that the meiotic phenotypes result
      from an inability to effectively repair DSBs. Our study further demonstrates that
      in Drosophila the Rad51-dependent homologous recombination pathway is not
      essential for DNA repair in the soma, unless exposed to DNA damaging agents. We
      therefore propose that under normal conditions a second, Rad51-independent,
      repair pathway prevents the lethal effects of DNA damage.

PMID- 14592984
TI  - Visualization of DNA-induced conformational changes in the DNA repair kinase DNA
      PKcs.
AB  - The catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs) is essential
      for the repair of double-stranded DNA breaks (DSBs) in non- homologous end
      joining (NHEJ) and during V(D)J recombination. DNA-PKcs binds single- and double
      stranded DNA in vitro, and in vivo the Ku heterodimer probably helps recruit it
      to DSBs with high affinity. Once loaded onto DNA, DNA-PKcs acts as a scaffold for
      other repair factors to generate a multiprotein complex that brings the two DNA
      ends together. Human DNA-PKcs has been analysed by electron microscopy in the
      absence and presence of double-stranded DNA, and the three-dimensional
      reconstruction of DNA-bound DNA-PKcs displays large conformational changes when
      compared with the unbound protein. DNA-PKcs seems to use a palm-like domain to
      clip onto the DNA, and this new conformation correlates with the activation of
      the kinase. We suggest that the observed domain movements might help the binding
      and maintenance of DNA-PKcs' interaction with DNA at the sites of damage, and
      that these conformational changes activate the kinase.

PMID- 14592985
TI  - Structural basis for recruitment of translesion DNA polymerase Pol IV/DinB to the
      beta-clamp.
AB  - Y-family DNA polymerases can extend primer strands across template strand lesions
      that stall replicative polymerases. The poor processivity and fidelity of these
      enzymes, key to their biological role, requires that their access to the primer
      template junction is both facilitated and regulated in order to minimize
      mutations. These features are believed to be provided by interaction with
      processivity factors, beta-clamp or proliferating cell nuclear antigen (PCNA),
      which are also essential for the function of replicative DNA polymerases. The
      basis for this interaction is revealed by the crystal structure of the complex
      between the 'little finger' domain of the Y-family DNA polymerase Pol IV and the
      beta-clamp processivity factor, both from Escherichia coli. The main interaction
      involves a C-terminal peptide of Pol IV, and is similar to interactions seen
      between isolated peptides and other processivity factors. However, this first
      structure of an entire domain of a binding partner with an assembled clamp
      reveals a substantial secondary interface, which maintains the polymerase in an
      inactive orientation, and may regulate the switch between replicative and Y
      family DNA polymerases in response to a template strand lesion.

PMID- 14592986
TI  - Mutations occur in the Ig Smu region but rarely in Sgamma regions prior to class
      switch recombination.
AB  - Nucleotide substitutions are found in recombined Ig switch (S) regions and also
      in unrecombined (germline, GL) Smicro segments in activated splenic B cells.
      Herein we examine whether mutations are also introduced into the downstream
      acceptor S regions prior to switch recombination, but find very few mutations in
      GL Sgamma3 and Sgamma1 regions in activated B cells. These data suggest that
      switch recombination initiates in the Smicro segment and secondarily involves the
      downstream acceptor S region. Furthermore, the pattern and specificity of
      mutations in GL and recombined Smicro segments differ, suggesting different
      repair mechanisms. Mutations in recombined Smicro regions show a strong bias
      toward G/C base pairs and WRCY/RGYW hotspots, whereas mutations introduced into
      the GL Smicro do not. Additionally, induction conditions affect mutation
      specificity within the GL Smicro segment. Mutations are most frequent near the S
      S junctions and decrease rapidly with distance from the junction. Finally, we
      find that mice expressing a transgene for terminal deoxynucleotidyl transferase
      (TdT) have nucleotide insertions at S-S junctions, indicating that the
      recombining DNA ends are accessible to end-processing enzyme activities.

PMID- 14592987
TI  - Alternative interactions between the Tn7 transposase and the Tn7 target DNA
      binding protein regulate target immunity and transposition.
AB  - The Tn7 transposon avoids inserting into a target DNA that contains a pre
      existing copy of Tn7. This phenomenon, known as 'target immunity', is established
      when TnsB, a Tn7 transposase subunit, binds to Tn7 sequences in the target DNA
      and mediates displacement of TnsC, a critical transposase activator, from the
      DNA. Paradoxically, TnsB-TnsC interactions are also required to promote
      transposon insertion. We have probed Tn7 target immunity by isolating TnsB
      mutants that mediate more frequent insertions into a potentially immune target
      DNA because they fail to provoke dissociation of TnsC from the DNA. We show that
      a single region of TnsB mediates the TnsB-TnsC interaction that underlies both
      target immunity and transposition, but that TnsA, the other transposase subunit,
      channels the TnsB-TnsC interaction toward transposition.

PMID- 14592988
TI  - Divergent evolutions of trinucleotide polymerization revealed by an archaeal CCA
      adding enzyme structure.
AB  - CCA-adding enzyme [ATP(CTP):tRNA nucleotidyltransferase], a template-independent
      RNA polymerase, adds the defined 'cytidine-cytidine-adenosine' sequence onto the
      3' end of tRNA. The archaeal CCA-adding enzyme (class I) and
      eubacterial/eukaryotic CCA-adding enzyme (class II) show little amino acid
      sequence homology, but catalyze the same reaction in a defined fashion. Here, we
      present the crystal structures of the class I archaeal CCA-adding enzyme from
      Archaeoglobus fulgidus, and its complexes with CTP and ATP at 2.0, 2.0 and 2.7 A
      resolutions, respectively. The geometry of the catalytic carboxylates and the
      relative positions of CTP and ATP to a single catalytic site are well conserved
      in both classes of CCA-adding enzymes, whereas the overall architectures, except
      for the catalytic core, of the class I and class II CCA-adding enzymes are
      fundamentally different. Furthermore, the recognition mechanisms of substrate
      nucleotides and tRNA molecules are distinct between these two classes, suggesting
      that the catalytic domains of class I and class II enzymes share a common origin,
      and distinct substrate recognition domains have been appended to form the two
      presently divergent classes.

PMID- 14592990
TI  - Sequences that direct significant levels of frameshifting are frequent in coding
      regions of Escherichia coli.
AB  - It is generally believed that significant ribosomal frameshifting during
      translation does not occur without a functional purpose. The distribution of two
      frameshift-prone sequences, A_AAA_AAG and CCC_TGA, in coding regions of
      Escherichia coli has been analyzed. Although a moderate level of selection
      against the first sequence is evident, 68 genes contain A_AAA_AAG and 19 contain
      CCC_TGA. The majority of those tested in their genomic context showed >1%
      frameshifting. Comparative sequence analysis was employed to assess a potential
      biological role for frameshifting in decoding these genes. Two new candidates, in
      pheL and ydaY, for utilized frameshifting have been identified in addition to
      those previously known in dnaX and nine insertion sequence elements. For the
      majority of the shift-prone sequences no functional role can be attributed to
      them, and the frameshifting is likely erroneous. However, none of frameshift
      sequences is in the 306 most highly expressed genes. The unexpected conclusion is
      that moderate frameshifting during expression of at least some other genes is not
      sufficiently harmful for cells to trigger strong negative evolutionary pressure.

PMID- 14592989
TI  - Exportin 6: a novel nuclear export receptor that is specific for profilin.actin
      complexes.
AB  - Active macromolecular transport between the nucleus and cytoplasm proceeds
      through nuclear pore complexes and is mostly mediated by transport receptors of
      the importin beta-superfamily. Here we identify exportin 6 (Exp6) as a novel
      family member from higher eukaryotes and show that it mediates nuclear export of
      profilin.actin complexes. Exp6 appears to contact primarily actin, but the
      interaction is greatly enhanced by the presence of profilin. Profilin thus
      functions not only as the nucleotide exchange factor for actin, but can also be
      regarded as a cofactor of actin export and hence as a suppressor of actin
      polymerization in the nucleus. Even though human and Drosophila Exp6 share only
      approximately 20% identical amino acid residues, their function in profilin.actin
      export is conserved. A knock-down of Drosophila Exp6 by RNA interference
      abolishes nuclear exclusion of actin and results in the appearance of nuclear
      actin paracrystals. In contrast to a previous report, we found no indications of
      a major and direct role for CRM1 in actin export from mammalian or insect nuclei.

PMID- 14592993
TI  - Rho family of guanine exchange factors (GEFs) in cellular activation: who's
      dancing? And with whom?

PMID- 14592991
TI  - Mss51p promotes mitochondrial Cox1p synthesis and interacts with newly
      synthesized Cox1p.
AB  - The post-transcriptional role of Mss51p in mitochondrial gene expression is of
      great interest since MSS51 mutations suppress the respiratory defect caused by
      shy1 mutations. SHY1 is a Saccharomyces cerevisiae homolog of human SURF1, which
      when mutated causes a cytochrome oxidase assembly defect. We found that MSS51 is
      required for expression of the mitochondrial reporter gene ARG8(m) when it is
      inserted at the COX1 locus, but not when it is at COX2 or COX3. Unlike the COX1
      mRNA-specific translational activator PET309, MSS51 has at least two targets in
      COX1 mRNA. MSS51 acts in the untranslated regions of the COX1 mRNA, since it was
      required to synthesize Arg8p when ARG8(m) completely replaced the COX1 codons.
      MSS51 also acts on a target specified by the COX1 coding region, since it was
      required to translate either COX1 or COX1:: ARG8(m) coding sequences from an
      ectopic COX2 locus. Mss51p was found to interact physically with newly
      synthesized Cox1p, suggesting that it could coordinate Cox1p synthesis with
      insertion into the inner membrane or cytochrome oxidase assembly.

PMID- 14592994
TI  - Sympathetic nerves and myocyte necrosis: more than meets the eye.

PMID- 14592995
TI  - Nitrate tolerance in hypertension: new insight into a century-old problem.

PMID- 14592996
TI  - On the role of the cAMP response element binding protein in long-term cardiac
      memory.

PMID- 14592997
TI  - Endogenous estrogens influence endothelial function in young men.
AB  - Males produce endogenous estrogen from testosterone via the enzyme aromatase.
      Previous studies have suggested a role for endogenous estrogens in cardiovascular
      function in men. We examined the effects of endogenous estrogen suppression via
      aromatase inhibition on endothelial function, systemic arterial compliance, and
      lipoprotein levels in healthy young men. Using a placebo-controlled double-blind
      randomized design, 20 healthy men, aged 18 to 32 years, were randomized to
      receive either the aromatase inhibitor anastrozole (1 mg) or matching placebo.
      Hormone, lipid levels, C-reactive protein (CRP), and homocysteine were measured.
      Endothelial function, determined by flow-mediated dilation of the brachial
      artery, and systemic arterial compliance were assessed at baseline and after 6
      weeks of treatment. There was a significant decrease in 17beta-estradiol
      concentrations with aromatase inhibition, from 85.4+/-4.2 to 64.3+/-8.1 pmol/L
      (mean+/-SD, P=0.042). Compared with baseline, a significant decrease in flow
      mediated dilation was observed in subjects taking anastrozole [median, 6.1%
      (range, 5.2 to 13.4) to 3.5% (2.0 to 5.7), P=0.034] but not in the placebo group.
      No changes were observed in nitroglycerin-induced endothelium-independent
      dilation in either group. There was no change in systemic arterial compliance
      with either aromatase therapy or placebo. There were no significant changes in
      lipoproteins, testosterone, DHEA, CRP, or homocysteine levels in either the
      anastrozole or placebo group. We conclude that suppression of endogenous
      estrogens with an aromatase inhibitor resulted in impairment of flow-mediated
      dilation without significant changes in lipoproteins, homocysteine, or CRP. Our
      results suggest that endogenous estrogens play a direct regulatory role in
      endothelial function in young healthy men.

PMID- 14592999
TI  - Biomechanically induced gene iex-1 inhibits vascular smooth muscle cell
      proliferation and neointima formation.
AB  - Mechanotransduction plays a prominent role in vascular pathophysiology but is
      incompletely understood. In this study, we report the biomechanical induction of
      the immediate early response gene iex-1 in vascular smooth muscle cells (SMCs).
      Mechanical induction of iex-1 was confirmed by Northern (30-fold induction after
      2 hours) and Western (6-fold induction after 24 hours) analyses. Expression of
      iex-1 was regulated by mechanical activation of nuclear factor (NF)-kappaB and
      abolished by overexpression of IkappaB in SMCs. The function of iex-1 in SMCs was
      explored by gene transfer using adenoviral vectors overexpressing iex-1. After 48
      hours of 4% cyclic mechanical strain, adenoviral vectors overexpressing iex-1
      infected cells had lower 3[H]-thymidine incorporation compared with AdGFP
      infected controls (71.3+/-8.5% versus 180.2+/-19.4% in controls; P<0.001).
      Overexpression of iex-1 suppressed mitogenesis induced by platelet-derived growth
      factor (208.1+/-108.3% versus 290.0+/-120.5% in controls; P<0.05). This was
      accompanied by reduced degradation of p27kip1, inhibition of Rb
      hyperphosphorylation, and reduced cell cycle progression. To investigate
      functional effects of iex-1 in vivo, we performed carotid artery mechanical
      injury and endothelial denudation in low-density lipoprotein receptor-deficient
      mice followed by intraluminal injection of adenoviral vectors (3x10(9) pfu in 50
      microL) for overexpression of iex-1 or gfp (control). Vascular overexpression of
      iex-1 reduced neointima formation 2 weeks after injury (intima/media ratio,
      0.23+/-0.04 versus 0.5+/-0.24 in controls; P<0.05). Our findings demonstrate that
      biomechanical strain induces iex-1 with subsequent antiproliferative effects in
      SMCs and that selective gene transfer of iex-1 inhibits the local vascular
      response after injury. These findings suggest that the induction of iex-1
      represents a novel negative biomechanical feedback mechanism limiting the
      vascular response to injury.

PMID- 14592998
TI  - Life-threatening thrombosis in mice with targeted Arg48-to-Cys mutation of the
      heparin-binding domain of antithrombin.
AB  - Antithrombin (AT) inhibits thrombin and some other coagulation factors in a
      reaction that is dramatically accelerated by binding of a pentasaccharide
      sequence present in heparin/heparan-sulfate to a heparin-binding site on AT.
      Based on the involvement of R47 in the heparin/AT interaction and the frequent
      occurrence of R47 mutations in AT deficiency patients, targeted knock-in of the
      corresponding R48C substitution in AT in mice was performed to generate a murine
      model of spontaneous thrombosis. The mutation efficiently abolished the effect of
      heparin-like molecules on coagulation inhibition in vitro and in vivo. Mice
      homozygous for the mutation (AT(m/m) mice) developed spontaneous, life
      threatening thrombosis, occurring as early as the day of birth. Only 60% of the
      AT(m/m) offspring reached weaning age, with further loss at different ages.
      Thrombotic events in adult homozygotes were most prominent in the heart, liver,
      and in ocular, placental, and penile vessels. In the neonate, spontaneous death
      invariably was associated with major thrombosis in the heart. This severe
      thrombotic phenotype underlines a critical function of the heparin-binding site
      of antithrombin and its interaction with heparin/heparan-sulfate moieties in
      health, reproduction, and survival, and represents an in vivo model for
      comparative analysis of heparin-derived and other antithrombotic molecules.

PMID- 14593000
TI  - Role of 14-3-3-mediated p38 mitogen-activated protein kinase inhibition in
      cardiac myocyte survival.
AB  - 14-3-3 family members are dimeric phosphoserine-binding proteins that regulate
      signal transduction, apoptotic, and checkpoint control pathways. Targeted
      expression of dominant-negative 14-3-3eta (DN-14-3-3) to murine postnatal cardiac
      tissue potentiates Ask1, c-jun N-terminal kinase (JNK), and p38 mitogen-activated
      protein kinase (MAPK) activation. DN-14-3-3 mice are unable to compensate for
      pressure overload, which results in increased mortality, dilated cardiomyopathy,
      and cardiac myocyte apoptosis. To evaluate the relative role of p38 MAPK activity
      in the DN-14-3-3 phenotype, we inhibited cardiac p38 MAPK activity by
      pharmacological and genetic methods. Intraperitoneal injection of SB202190, an
      inhibitor of p38alpha and p38beta MAPK activity, markedly increased the ability
      of DN-14-3-3 mice to compensate for pressure overload, with decreased mortality.
      DN-14-3-3 mice were bred with transgenic mice in which dominant-negative p38alpha
      (DN-p38alpha) or dominant-negative p38beta (DN-p38beta) MAPK expression was
      targeted to the heart. Compound transgenic DN-14-3-3/DN-p38beta mice, and to a
      lesser extent compound transgenic DN-14-3-3/DN-p38alpha mice, exhibited reduced
      mortality and cardiac myocyte apoptosis in response to pressure overload,
      demonstrating that DN-14-3-3 promotes cardiac apoptosis due to stimulation of p38
      MAPK activity.

PMID- 14593001
TI  - Using DNA microarray to identify Sp1 as a transcriptional regulatory element of
      insulin-like growth factor 1 in cardiac muscle cells.
AB  - High throughput gene expression profiling with DNA microarray provides an
      opportunity to analyze transcriptional regulation of hundreds or thousands of
      similarly regulated genes. Transcriptional regulation of gene expression plays an
      important role in myocardial remodeling. We have studied cardiac muscle gene
      expression with DNA microarray and used a computational strategy to identify
      common promoter motifs that respond to insulin-like growth factor 1 (IGF-1)
      stimulation in cardiac muscle cells. The analysis showed that the Sp1 binding
      site is a likely target of IGF-1 action. Further experiments with gel shift assay
      indicated that IGF-1 regulated the Sp1 site in cardiomyocytes, by increasing the
      abundance of Sp1 and Sp3 proteins. Using firefly luciferase as reporter gene,
      additional experiments showed that IGF-1 activated the promoter of cyclin D3 and
      Glut1. Both promoters contain one Sp1 site. The effect of IGF-1 on these two
      promoters was abolished with siRNA for Sp1. Thus, the transcriptional activation
      of these two promoters by IGF-1 requires the induction of Sp1 protein. These
      experiments suggest that the global transcriptional regulatory actions of IGF-1
      involve activation of the Sp1 site in cardiac muscle. The computational model we
      have developed is a prototypical method that may be further developed to identify
      unique cis- and trans-acting elements in response to hormonal stimulation during
      cardiac muscle growth, repair, and remodeling in normal and abnormal cardiac
      muscle.

PMID- 14593002
TI  - Essential role for vascular gelatinase activity in relaxin-induced renal
      vasodilation, hyperfiltration, and reduced myogenic reactivity of small arteries.
AB  - During pregnancy, relaxin stimulates nitric oxide (NO)-dependent renal
      vasodilation, hyperfiltration and reduced myogenic reactivity of small renal
      arteries via the endothelial ETB receptor subtype. Our objective in this study
      was to elucidate the mechanisms by which relaxin stimulates the endothelial ETB
      receptor/NO vasodilatory pathway. Using chronically instrumented conscious rats,
      we demonstrated that a specific peptide inhibitor of the gelatinases MMP-2 and 
      9, cyclic CTTHWGFTLC (cyclic CTT), but not the control peptide, STTHWGFTLS (STT),
      completely reversed renal vasodilation and hyperfiltration in relaxin-treated
      rats. Comparable findings were observed with a structurally different and well
      established, general antagonist of MMPs, GM6001. In contrast, phosphoramidon, an
      inhibitor of endothelin-converting enzyme, did not significantly change the renal
      vasodilatory response to relaxin administration. When small renal arteries were
      incubated with either of the general MMP inhibitors, GM6001 or TIMP-2 (tissue
      inhibitor of MMP), or with the specific gelatinase inhibitor, cyclic CTT, the
      reduced myogenic reactivity of these blood vessels from relaxin-treated
      nonpregnant and midterm pregnant rats was totally abolished. Moreover, a
      neutralizing antibody specific for MMP-2 completely abrogated the reduced
      myogenic reactivity of small renal arteries from relaxin-treated nonpregnant and
      midterm pregnant rats. In contrast, phosphoramidon did not significantly affect
      the reduction in myogenic reactivity. Using gelatin zymography, we showed
      increased pro and active MMP-2 activity in small renal arteries from relaxin
      treated nonpregnant and midterm pregnant rats relative to the control animals.
      Thus, inhibitors of MMPs in general and of gelatinases in particular reverse the
      renal vascular changes induced by pregnancy or relaxin administration to
      nonpregnant rats. Finally, the typical reduction in myogenic reactivity of small
      renal arteries from relaxin-treated nonpregnant rats was absent in ETB receptor
      deficient rats, despite an increase in vascular MMP-2 activity. These results
      indicate an essential role for vascular gelatinase, which is in series with, and
      upstream of, the endothelial ETB receptor/NO signaling pathway in the renal
      vasodilatory response to relaxin and pregnancy.

PMID- 14593004
TI  - Improving clinical research.

PMID- 14593003
TI  - Pulsatile versus oscillatory shear stress regulates NADPH oxidase subunit
      expression: implication for native LDL oxidation.
AB  - Shear stress regulates endothelial nitric oxide and superoxide (O2-*) production,
      implicating the role of NADPH oxidase activity. It is unknown whether shear
      stress regulates the sources of reactive species production, consequent low
      density lipoprotein (LDL) modification, and initiation of inflammatory events.
      Bovine aortic endothelial cells (BAECs) in the presence of 50 microg/mL of native
      LDL were exposed to (1) pulsatile flow with a mean shear stress (tau(ave)) of 25
      dyne/cm2 and (2) oscillating flow at tau(ave) of 0. After 4 hours, aliquots of
      culture medium were collected for high-performance liquid chromatography analyses
      of electronegative LDL species, described as LDL- and LDL2-. In response to
      oscillatory shear stress, gp91phox mRNA expression was upregulated by 2.9+/-0.3
      fold, and its homologue, Nox4, by 3.9+/-0.9-fold (P<0.05, n=4), with a
      corresponding increase in O2-* production rate. The proportion of LDL- and LDL2-
      relative to static conditions increased by 67+/-17% and 30+/-7%, respectively,
      with the concomitant upregulation of monocyte chemoattractant protein-1
      expression and increase in monocyte/BAEC binding (P<0.05, n=5). In contrast,
      pulsatile flow downregulated both gp91phox and Nox4 mRNA expression (by 1.8+/-0.2
      fold and 3.0+/-0.12-fold, respectively), with an accompanying reduction in O2-*
      production, reduction in the extent of LDL modification (51+/-12% for LDL- and
      30+/-7% for LDL2-), and monocyte/BAEC binding. The flow-dependent LDL oxidation
      is determined in part by the NADPH oxidase activity. The formation of modified
      LDL via O2-* production may also affect the regulation of monocyte
      chemoattractant protein-1 expression and monocyte/BAEC binding.

PMID- 14593005
TI  - Practising just medicine in an unjust world.

PMID- 14593006
TI  - BMJ Publishing Group to launch an international campaign to promote academic
      medicine.

PMID- 14593007
TI  - The management of acute mania.

PMID- 14593010
TI  - Cochrane plans to allay fears over industry influence.

PMID- 14593008
TI  - Treatment of postnatal depression.

PMID- 14593011
TI  - Initiative gets under way to help scientific editors regulate themselves.

PMID- 14593013
TI  - Ratio of girls to boys in India continues to decline.

PMID- 14593014
TI  - Health secretary demands patients have equal access to cancer drugs.

PMID- 14593018
TI  - NHS criticised over suicide of mentally ill doctor.

PMID- 14593020
TI  - US ban on "partial birth" abortions could outlaw other forms as well.

PMID- 14593022
TI  - NICE guidance recommends fewer but earlier antenatal check ups.

PMID- 14593021
TI  - European parliament tries to stamp out trafficking in human organs.

PMID- 14593024
TI  - Serbian doctors strike for a 40% pay increase.

PMID- 14593025
TI  - Health insurance fraud rises in the United States.

PMID- 14593029
TI  - UK government denies that smallpox vaccination plans have fallen short of target.

PMID- 14593031
TI  - Florida governor orders reinsertion of feeding tube.

PMID- 14593032
TI  - Adherence to advance directives in critical care decision making: vignette study.
AB  - OBJECTIVE: To explore health professionals' decision making in a critical care
      scenario when there is an advance directive. DESIGN: Qualitative study. SETTING:
      Scotland. PARTICIPANTS: Interviewees (n = 12) comprising general practitioners,
      hospital specialists, and nurses, and six focus groups (n = 34 participants)
      comprising general practitioners, geriatricians (consultants and specialist
      registrars), hospital nurses, and hospice nurses. RESULTS: When presented with an
      advance directive that applied to the same hypothetical scenario, health
      professionals came to divergent conclusions as to the "right thing to do."
      Arguments opposing treatment centred on the supremacy of autonomy as an ethical
      principle. Other arguments were that the decision to treat was consistent with
      the terms of the advance directive, or that, notwithstanding the advance
      directive, the patient's quality of life was sufficient to warrant treatment.
      CONCLUSION: Advance directives are open to widely varying interpretation. Some of
      this variability is related to the ambiguity of the directive's terminology
      whereas some is related to the willingness of health professionals to make
      subjective value judgments concerning quality of life.

PMID- 14593033
TI  - Effect of the critical care outreach team on patient survival to discharge from
      hospital and readmission to critical care: non-randomised population based study.
AB  - OBJECTIVES: To determine the effect of the critical care outreach team on patient
      survival to discharge from hospital after discharge from critical care and
      readmission to critical care. DESIGN: Non-randomised population based study.
      SETTING: Tertiary referral teaching hospital with 1200 beds. PARTICIPANTS:
      Patients discharged from the critical care unit after their first or only
      admission for two study periods, 26 February 2000 to 25 February 2001 and 26
      February 2001 to 25 February 2002. MAIN OUTCOME MEASURES: Survival to discharge
      from hospital after discharge from critical care and readmission to critical
      care. RESULTS: The introduction of a critical care outreach team improved
      survival to discharge from hospital after discharge from critical care by 6.8%
      (risk ratio 1.08). Readmission to critical care decreased by 6.4% (0.48).
      CONCLUSIONS: The activity of the critical care outreach team seems to improve
      patient survival to discharge from hospital and may reduce the number of
      readmissions to critical care.

PMID- 14593034
TI  - Descriptive survey of non-commercial randomised controlled trials in the United
      Kingdom, 1980-2002.
AB  - OBJECTIVES: To describe the characteristics of randomised controlled trials
      supported by the main non-commercial sources of funding in the United Kingdom
      between 1980 and 2002. DESIGN: Descriptive survey. SETTING: Randomised controlled
      trials funded by the Medical Research Council, NHS research and development
      programme, Department of Health, Chief Scientist Office in Scotland, and medical
      research charities. PARTICIPANTS: 1464 randomised controlled trials supported by
      the main non-commercial sources of funding. RESULTS: Support for randomised
      controlled trials by the main sources of non-commercial funding in the United
      Kingdom has fallen in recent years, without any concomitant increase in the
      sample sizes of these studies. Drug trials in a limited range of health problems
      have dominated among the studies supported by the Medical Research Council and
      medical research charities. Until recently, the NHS research and development
      programme supported randomised controlled trials of various healthcare
      interventions, in a wide range of health problems, but between 1999 and 2002 many
      of the subprogrammes that had commissioned trials were discontinued. CONCLUSIONS:
      The future of non-commercial randomised controlled trials in the United Kingdom
      has been threatened by the discontinuation or demise of national and regional NHS
      research and development programmes. Support also seems to be declining from the
      Medical Research Council and the medical research charities. It is unclear what
      the future holds for randomised controlled trials that address issues of no
      interest to industry but are of great importance to patients and practitioners.

PMID- 14593037
TI  - Privacy of patients' information in hospital lifts: observational study.

PMID- 14593036
TI  - Secondhand effects of alcohol use among university students: computerised survey.

PMID- 14593035
TI  - Decline in mortality, AIDS, and hospital admissions in perinatally HIV-1 infected
      children in the United Kingdom and Ireland.
AB  - OBJECTIVE: To describe changes in demographic factors, disease progression,
      hospital admissions, and use of antiretroviral therapy in children with HIV.
      DESIGN: Active surveillance through the national study of HIV in pregnancy and
      childhood (NSHPC) and additional data from a subset of children in the
      collaborative HIV paediatric study (CHIPS). SETTING: United Kingdom and Ireland.
      PARTICIPANTS: 944 children with perinatally acquired HIV-1 under clinical care.
      MAIN OUTCOME MEASURES: Changes over time in progression to AIDS and death,
      hospital admission rates, and use of antiretroviral therapy. RESULTS: 944
      children with perinatally acquired HIV were reported in the United Kingdom and
      Ireland by October 2002; 628 (67%) were black African, 205 (22%) were aged > or =
      10 years at last follow up, 193 (20%) are known to have died. The proportion of
      children presenting who were born abroad increased from 20% in 1994-5 to 60%
      during 2000-2. Mortality was stable before 1997 at 9.3 per 100 child years at
      risk but fell to 2.0 in 2001-2 (trend P < 0.001). Progression to AIDS also
      declined (P < 0.001). From 1997 onwards the proportion of children on three or
      four drug antiretroviral therapy increased. Hospital admission rates declined by
      80%, but with more children in follow up the absolute number of admissions fell
      by only 26%. CONCLUSION: In children with HIV infection, mortality, AIDS, and
      hospital admission rates have declined substantially since the introduction of
      three or four drug antiretroviral therapy in 1997. As infected children in the
      United Kingdom and Ireland are living longer, there is an increasing need to
      address their medical, social, and psychological needs as they enter adolescence
      and adult life.

PMID- 14593038
TI  - Risk of suicide and spouse's psychiatric illness or suicide: nested case-control
      study.

PMID- 14593039
TI  - Screening older people for impaired vision in primary care: cluster randomised
      trial.
AB  - OBJECTIVE: To determine the effectiveness of screening for visual impairment in
      people aged 75 or over as part of a multidimensional screening programme. DESIGN:
      Cluster randomised trial. SETTING: General practices in the United Kingdom
      participating in the MRC trial of assessment and management of older people in
      the community. PARTICIPANTS: 4340 people aged 75 years or over randomly sampled
      from 20 general practices, excluding people resident in hospitals or nursing
      homes. INTERVENTION: Visual acuity testing and referral to eye services for
      people with visual impairment. Universal screening (assessment and visual acuity
      testing) was compared with targeted screening, in which only participants with a
      range of health related problems were offered an assessment that included acuity
      screening. MAIN OUTCOME MEASURES: Proportion of people with visual acuity less
      than 6/18 in either eye; mean composite score of 25 item version of the National
      Eye Institute visual function questionnaire. RESULTS: Three to five years after
      screening, the relative risk of having visual acuity < 6/18 in either eye,
      comparing universal with targeted screening, was 1.07 (95% confidence interval
      0.84 to 1.36; P = 0.58). The mean composite score of the visual function
      questionnaire was 85.6 in the targeted screening group and 86.0 in the universal
      group (difference 0.4, 95% confidence interval -1.7 to 2.5, P = 0.69).
      CONCLUSIONS: Including a vision screening component by a practice nurse in a
      pragmatic trial of multidimensional screening for older people did not lead to
      improved visual outcomes.

PMID- 14593040
TI  - DSM depression and anxiety criteria and severity of symptoms in primary care:
      cross sectional study.

PMID- 14593041
TI  - Objective assessment of technical skills in surgery.

PMID- 14593042
TI  - ABC of subfertility. Counselling.

PMID- 14593043
TI  - Resuscitating clinical research in the United Kingdom.

PMID- 14593044
TI  - Cancer care in the United Kingdom: new solutions are needed.

PMID- 14593049
TI  - What is a good death? Good death will happen if life was good.

PMID- 14593051
TI  - What is a good death? We must learn to live in the light of our mortality.

PMID- 14593053
TI  - What is a good death? Good death may be possible in emergency departments.

PMID- 14593054
TI  - What is a good death? Pathologists could provide new spaces to say goodbye to the
      dead.

PMID- 14593055
TI  - Survival predictions may hasten death.

PMID- 14593056
TI  - What is a good death? Grandmother's death was a good example.

PMID- 14593057
TI  - Responding to unexpected events: maybe skills for this case were missing.

PMID- 14593058
TI  - Responding to unexpected events: patients have to be treated as individuals.

PMID- 14593059
TI  - Everyone has own spirituality.

PMID- 14593060
TI  - Issues related to humanities are close to core of science.

PMID- 14593061
TI  - Respiratory hazards of "nail sculpture".

PMID- 14593062
TI  - Tamoxifen is unproved for gynaecomastia.

PMID- 14593063
TI  - Small risk ratios may have strong public health impact.

PMID- 14593064
TI  - ATAC trial did not report interim results.

PMID- 14593065
TI  - Costs and effectiveness of prehospital thrombolysis need to be clear.

PMID- 14593066
TI  - Equality for people with disabilities in medicine.

PMID- 14593067
TI  - Non-pharmacological options may have role in postmenopausal osteoporosis.

PMID- 14593068
TI  - A career in nuclear medicine.

PMID- 14593072
TI  - Dictyostelium stress-activated protein kinase alpha, a novel stress-activated
      mitogen-activated protein kinase kinase kinase-like kinase, is important for the
      proper regulation of the cytoskeleton.
AB  - Mitogen-activated protein kinase cascades regulate various cellular functions,
      including growth, cell differentiation, development, and stress responses. We
      have identified a new Dictyostelium kinase (stress-activated protein kinase
      [SAPK]alpha), which is related to members of the mixed lineage kinase class of
      mitogen-activated protein kinase kinases. SAPKalpha is activated by osmotic
      stress, heat shock, and detachment from the substratum and by a membrane
      permeable cGMP analog, a known regulator of stress responses in Dictyostelium.
      SAPKalpha is important for cellular resistance to stresses, because SAPKalpha
      null cells exhibit reduced viability in response to osmotic stress. We found that
      SAPKalpha mutants affect cellular processes requiring proper regulation of the
      actin cytoskeleton, including cell motility, morphogenesis, cytokinesis, and cell
      adhesion. Overexpression of SAPKalpha results in highly elevated basal and
      chemoattractant-stimulated F-actin levels and strong aggregation and
      developmental defects, including a failure to polarize and chemotax, and abnormal
      morphogenesis. These phenotypes require a kinase-active SAPKalpha. SAPKalpha null
      cells exhibit reduced chemoattractant-stimulated F-actin levels, cytokinesis,
      developmental and adhesion defects, and a motility defect that is less severe
      than that exhibited by SAPKalpha-overexpressing cells. SAPKalpha colocalizes with
      F-actin in F-actin-enriched structures, including membrane ruffles and
      pseudopodia during chemotaxis. Although SAPKalpha is required for these F-actin
      mediated processes, it is not detectably activated in response to chemoattractant
      stimulation.

PMID- 14593074
TI  - Pituitary adenylate cyclase-activating peptide: a pivotal modulator of steroid
      induced reproductive behavior in female rodents.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) regulates the
      secretion of GnRH into the hypothalamic hypophysial portal system and sensitizes
      the pituitary for release of hormones that trigger ovulation. Because
      reproductive behavior is synchronized with GnRH release, the present study was
      undertaken to determine whether PACAP in the ventromedial nucleus (VMN) plays a
      role in receptivity. To this end, we used rat and mouse reproductive behavioral
      models to determine the biological relationship between PACAP and steroid
      receptor function in females. We provide evidence for the requirement of PACAP in
      the VMN for progesterone (P)-dependent sexual behavior in estrogen (E)-primed
      females. We clarify the biological and molecular mechanisms of PACAP activity by
      showing 1) that inhibition of endogenous PACAP suppresses P receptor (PR)
      dependent sexual behavior facilitated by the steroid P or D1-like agonist
      SKF38393 and 2) that PR, steroid receptor coactivators-1 and -2, and new protein
      synthesis are essential for ligand independent PACAP-facilitated behavior. These
      findings are consistent with convergence of PACAP-mediated cellular signals on PR
      for genomic activation and subsequent behavioral changes. Further, we show that
      steroids regulate both endogenous PACAP mRNA in the VMN and immunoreactive PACAP
      in the medial basal hypothalamus and cerebral spinal fluid for ligand-dependent,
      steroid receptor-dependent receptivity. The present findings delineate a novel,
      steroid-dependent mechanism within the female hypothalamus by which the
      neuropeptide PACAP acts as a feed-forward, paracrine, and/or autocrine factor for
      synchronization of behavior coordinate with hypothalamic control of ovulation.

PMID- 14593073
TI  - Receptor internalization in yeast requires the Tor2-Rho1 signaling pathway.
AB  - Efficient internalization of proteins from the cell surface is essential for
      regulating cell growth and differentiation. In a screen for yeast mutants
      defective in ligand-stimulated internalization of the alpha-factor receptor, we
      identified a mutant allele of TOR2, tor2G2128R. Tor proteins are known to
      function in translation initiation and nutrient sensing and are required for cell
      cycle progression through G1. Yeast Tor2 has an additional role in regulating the
      integrity of the cell wall by activating the Rho1 guanine nucleotide exchange
      factor Rom2. The endocytic defect in tor2G2128R cells is due to disruption of
      this Tor2 unique function. Other proteins important for cell integrity, Rom2 and
      the cell integrity sensor Wsc1, are also required for efficient endocytosis. A
      rho1 mutant specifically defective in activation of the glucan synthase Fks1/2
      does not internalize alpha-factor efficiently, and fks1Delta cells exhibit a
      similar phenotype. Removal of the cell wall does not inhibit internalization,
      suggesting that the function of Rho1 and Fks1 in endocytosis is not through cell
      wall synthesis or structural integrity. These findings reveal a novel function
      for the Tor2-Rho1 pathway in controlling endocytosis in yeast, a function that is
      mediated in part through the plasma membrane protein Fks1.

PMID- 14593075
TI  - Cell cycle progression and activation of Akt kinase are required for insulin-like
      growth factor I-mediated suppression of apoptosis in granulosa cells.
AB  - Ovarian follicle development is dependent on growth factors that stimulate cell
      proliferation and act as survival factors to prevent apoptosis of follicle cells.
      We examined the mechanism of the protective effect of IGF-I against Fas ligand
      induced apoptosis of granulosa cells and its relationship to cell proliferation.
      IGF-I activated both the phosphoinositide 3'-OH kinase (PI3K) and the MAPK
      pathways. Experiments using specific inhibitors of these pathways showed that
      protection by IGF-I was mediated by the PI3K pathway and not the MAPK pathway.
      Recombinant adenoviruses were used to test whether the downstream target of PI3K
      activation, Akt kinase, was required for protection against apoptosis. Expression
      of dominant negative Akt prevented protection by IGF-I whereas expression of
      constitutively active Akt (myrAkt) mimicked the effect of IGF-I. Treatment with
      IGF-I, or expression of myrAkt, increased progression from G(0)/G(1) to S phase
      of the cell cycle whereas expression of dominant negative Akt inhibited G(0)/G(1)
      to S phase progression and prevented the stimulatory effect of IGF-I. We tested
      whether cell cycle progression was required for protection from apoptosis using
      the cyclin-dependent kinase-2 inhibitor roscovitine, which blocks cells at the
      G(1)/S transition. Roscovitine prevented the protective effect of IGF-I and
      myrAkt expression against apoptosis. Therefore, activation of Akt is not
      sufficient to protect granulosa cells from apoptosis in the absence of cell cycle
      progression. In summary, IGF-I protects granulosa cells from apoptosis by
      activation of the PI3K/Akt pathway. This protective effect can occur only when
      progression from G(1) to S phase of the cell cycle regulated by the PI3K/Akt
      pathway is unperturbed.

PMID- 14593076
TI  - Antiandrogen effects of mifepristone on coactivator and corepressor interactions
      with the androgen receptor.
AB  - Mifepristone is a potent antagonist of steroid hormone receptors such as
      glucocorticoid and progesterone receptors. We investigated the potential for
      mifepristone to act as an antiandrogen and compared it with partial androgen
      receptor (AR) agonists and antagonists, in particular bicalutamide. Mifepristone
      was an effective antiandrogen in vitro that inhibited transcription from three
      androgen-responsive promoters and blocked the agonist R1881 in a dose-dependent
      manner. Like bicalutamide, mifepristone also antagonized the action of androgen
      receptor with a (T877A) mutation. Mifepristone competed effectively with R1881
      with a relative binding affinity comparable to that of cyproterone acetate, and
      much higher than that of hydroxyflutamide and bicalutamide in a binding assay.
      Mifepristone could effectively induce the binding of the herpes simplex viral
      protein 16/AR fusion protein to the hormone response elements in the murine
      mammary tumor virus-luciferase reporter. With either wild-type or T877A mutant
      AR, mifepristone alone was unable to induce any detectable interaction with
      coactivators transcriptional intermediary factor-2 or beta-catenin but could
      inhibit the R1881-induced binding of AR to transcriptional intermediary factor-2
      and beta-catenin. Similarly, mifepristone could inhibit the R1881-induced N/C
      terminal interaction in a dose-dependent manner even though mifepristone alone
      has no effect on the N/C-terminal interaction of AR. We found that mifepristone
      could induce a strong interaction between AR and corepressors nuclear receptor
      corepressor and silencing mediator for retinoid and thyroid hormone receptors in
      both transactivation and two-hybrid assays to a greater degree than
      hydroxyflutamide, cyproterone acetate, and bicalutamide. The AR-corepressor
      interaction was also seen in coimmunoprecipitation assays. Finally, mifepristone
      at high concentrations induced a low level of prostate-specific antigen
      expression in LNCaP and antagonized prostate-specific antigen expression induced
      by R1881. Mifepristone also antagonized R1881 action on the growth of LNCaP
      prostate cancer cells.

PMID- 14593077
TI  - Inhibition of aromatase transcription via promoter II by short heterodimer
      partner in human preadipocytes.
AB  - Estrogen synthesis from C19 precursors is catalyzed by aromatase cytochrome P450.
      Overexpression of aromatase through atypical promoter usage (use of promoter II)
      in adipose tissue contributes to breast cancer development and progression. One
      tumor-derived factor that appears to contribute to this process is prostaglandin
      E2 (PGE2). A factor that regulates aromatase expression downstream of PGE2 is
      liver receptor homolog-1 (LRH-1). In a study of factors that inhibit LRH-1, we
      have examined the ability of short heterodimer partner (SHP) to inhibit aromatase
      transcription mediated by LRH-1 in preadipocytes. RT-PCR analysis indicated that
      both LRH-1 and SHP are expressed in human preadipocytes. To assess the effect of
      SHP on aromatase transcription, a transient transfection system was established
      using 3T3-L1 preadipocytes. Expression of SHP completely inhibited activity of an
      aromatase promoter II reporter gene induced by LRH-1. The combined treatment of
      forskolin and phorbol ester (which mimic PGE2) as well as LRH-1, which maximally
      induced reporter gene expression (140-fold), was also completely inhibited by
      SHP. This effect of SHP was mediated by inhibition of LRH-1 transcriptional
      activity, as measured by activity of GAL4-LRH-1 fusion constructs, and by
      inhibition of LRH-1 binding to promoter II. We conclude that SHP is a potent
      inhibitor of aromatase transcription in preadipocytes. Modulation of SHP
      expression and/or activity in adipose tissue may therefore have significant
      effects on aromatase expression and estrogen production in breast adipose tissue.

PMID- 14593078
TI  - The Rab-binding protein Noc2 is associated with insulin-containing secretory
      granules and is essential for pancreatic beta-cell exocytosis.
AB  - The small GTPases Rab3 and Rab27 are associated with secretory granules of
      pancreatic beta-cells and regulate insulin exocytosis. In this study, we
      investigated the role of Noc2, a potential partner of these two GTPases, in
      insulin secretion. In the beta-cell line INS-1E wild-type Noc2, Noc265E, and
      Noc258A, a mutant capable of interacting with Rab27 but not Rab3, colocalized
      with insulin-containing vesicles. In contrast, two mutants (Noc2138S,141S and
      Noc2154A,155A,156A) that bind neither Rab3 nor Rab27 did not associate with
      secretory granules and were uniformly distributed throughout the cell cytoplasm.
      Overexpression of wild-type Noc2, Noc265E, or Noc258A inhibited hormone secretion
      elicited by insulin secretagogues. In contrast, overexpression of the mutants not
      targeted to secretory granules was without effect. Silencing of the Noc2 gene by
      RNA interference led to a strong impairment in the capacity of INS-1E cells to
      respond to insulin secretagogues, indicating that appropriate levels of Noc2 are
      essential for pancreatic beta-cell exocytosis. The defect was already detectable
      in the early secretory phase (0-10 min) but was particularly evident during the
      sustained release phase (10-45 min). Protein-protein binding studies revealed
      that Noc2 is a potential partner of Munc13, a component of the machinery that
      controls vesicle priming and insulin exocytosis. These data suggest that Noc2 is
      involved in the recruitment of secretory granules at the plasma membrane possibly
      via the interaction with Munc13.

PMID- 14593080
TI  - Modification of nociception and morphine tolerance by the selective opiate
      receptor-like orphan receptor antagonist (-)-cis-1-methyl-7-[[4-(2,6
      dichlorophenyl)piperidin-1-yl]methyl]-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ol
      (SB-612111).
AB  - (-)-cis-1-Methyl-7-[[4-(2,6-dichlorophenyl)piperidin-1-yl]methyl]-6,7,8,9
      tetrahydro-5H-benzocyclohepten-5-ol (SB-612111) is a novel human opiate receptor
      like orphan receptor (ORL-1) antagonist that has high affinity for the clonal
      human ORL-1 receptor (hORL-1 K(i) = 0.33 nM), selectivity versus mu-(174-fold),
      delta-(6391-fold), and kappa (486-fold)-opioid receptors and is able to inhibit
      nociceptin signaling via hORL-1 in a whole cell gene reporter assay. SB-612111
      has no measurable antinociceptive effects in vivo in the mouse hot-plate test
      after intravenous administration but is able to antagonize the antimorphine
      action of nociceptin [ED(50) = 0.69 mg/kg, 95% confidence limit (CL) = 0.34
      1.21]. SB-62111 administration can also reverse tolerance to morphine in this
      model, established via repeated morphine administration. In addition, intravenous
      SB-612111 can antagonize nociceptin-induced thermal hyperalgesia in a dose
      dependent manner (ED(50) = 0.62 mg/kg i.v., 95% CL = 0.22-1.89) and is effective
      per se at reversing thermal hyperalgesia in the rat carrageenan inflammatory pain
      model. These data show that an ORL-1 receptor antagonist may be a useful adjunct
      to chronic pain therapy with opioids and can be used to treat conditions in which
      thermal hyperalgesia is a significant component of the pain response.

PMID- 14593079
TI  - From proteomic analysis to clinical significance: overexpression of cytokeratin
      19 correlates with hepatocellular carcinoma metastasis.
AB  - To better understand the mechanism underlying the hepatocellular carcinoma (HCC)
      metastasis and to search potential markers for HCC prognosis, differential
      proteomic analysis on two well-established HCC cell strains with high and low
      metastatic potentials, MHCC97-H and MHCC97-L, was conducted using two-dimensional
      gel electrophoresis followed by matrix-assisted laser desorption/time-of-flight
      mass spectrometry. Cytokeratin 19 (CK19) was identified and found to be
      overexpressed in MHCC97-H as compared with MHCC97-L. This result was further
      confirmed by two-dimensional Western blot analysis and immunofluorescence assay.
      Furthermore, one-dimensional Western blot analysis showed consistently increased
      CK19 expression in progressively more metastatic cells. Immunohistochemical study
      on 102 human HCC specimens revealed that more patients in the CK19-positive group
      had overt intrahepatic metastases (satellite nodules, p < 0.05; vascular tumor
      emboli, p < 0.001; tumor node metastatis staging, p < 0.001). CK19 fragment CYFRA
      21-1 levels measured in sera from nude mice model of human HCC metastasis with
      radioimmunoassay increased in parallel with tumor progression and rose remarkably
      when pulmonary metastases occurred. The results demonstrated that overexpression
      of CK19 in HCC cells is related to metastatic behavior. Serum CK19 level might
      reflect the pathological progression in some HCC and may be a useful marker for
      predicting tumor metastasis and a therapeutic target for the treatment of HCC
      patients with metastases.

PMID- 14593081
TI  - Increased reactivity of murine mesenteric veins to adrenergic agonists:
      functional evidence supporting increased alpha1-adrenoceptor reserve in veins
      compared with arteries.
AB  - These studies examined adrenergic reactivity of mesenteric arteries and veins
      from deoxycorticosterone acetate-salt (DOCA-salt) hypertensive and sham control
      mice. We measured constrictions in unpressurized arteries and veins by monitoring
      vessel diameter using computer-assisted video micros-copy in vitro. Veins were
      more sensitive than arteries to the constricting effects of norepinephrine (NE)
      and phenylephrine (PE), but the alpha2-agonists clonidine and UK 14,304 [5-bromo
      6-(2-imidazolin-2-yl-amino)-quinoxaline] did not constrict arteries or veins.
      Reactivity was not altered in arteries or veins from DOCA-salt mice. We next
      investigated the mechanism of increased venous reactivity to NE and PE by
      studying desensitization to maximum concentrations of NE and PE. Sham arteries
      desensitized to NE and PE more than DOCA-salt arteries, whereas DOCA-salt and
      sham veins maintained 80% of the initial NE and PE constriction. To determine
      whether the increased reactivity and resistance to desensitization in veins was
      due to a greater alpha-adrenoceptor reserve, vessels were incubated with the
      alkylating agent phenoxybenzamine (PBZ; 0.3, 3, 10, and 30 nM). The NE-elicited
      initial constriction was reduced by PBZ (3, 10, and 30 nM) in sham but only by
      PBZ (30 nM) in DOCA-salt veins. All doses of PBZ blocked NE responses in sham and
      DOCA-salt arteries. These data suggest that mesenteric veins express more alpha1
      adrenoceptors than arteries, accounting for greater reactivity and resistance to
      desensitization compared with arteries.

PMID- 14593082
TI  - Neuroprotective properties of topiramate in the lithium-pilocarpine model of
      epilepsy.
AB  - The lithium-pilocarpine model reproduces the main characteristics of human
      temporal lobe epilepsy. After status epilepticus (SE), rats exhibit a latent
      seizure-free phase characterized by development of extensive damage in limbic
      areas and occurrence of spontaneous recurrent seizures. Neuroprotective and
      antiepileptogenic effects of topiramate were investigated in this model. SE was
      induced in adult male rats by LiCl (3 mEq/kg) followed 20 h later by pilocarpine
      (25 mg/kg). Topiramate (10, 30, or 60 mg/kg) was injected at 1 and 10 h of SE.
      Injections were repeated twice a day for six additional days. Another group
      received two injections of diazepam on the day of SE and of vehicle for 6 days.
      Neuronal damage was assessed at 14 days after SE by cell counting on thionin
      stained sections. Occurrence of spontaneous recurrent seizures (SRS) was
      videorecorded for 10 h per day in other groups of rats. In diazepam-treated rats,
      the number of neurons was dramatically reduced after SE in all subregions of
      hippocampus and layers II-IV of ventral cortices. At all doses, topiramate
      induced a 24 to 30% neuroprotection in layer CA1 of hippocampus (p < 0.05). In
      CA3b, the 30-mg/kg dose prevented neuronal death. All rats subjected to SE became
      epileptic. The latency (14-17 days) to and frequency of SRS were similar in
      topiramate- and diazepam-treated rats. The high mortality in the 30 mg/kg
      topiramate group (84%) was possibly the result of interaction between lithium and
      topiramate. In conclusion, topiramate displayed neuroprotective properties only
      in CA1 and CA3 that were not sufficient to prevent epileptogenesis.

PMID- 14593083
TI  - Recovery of sensorimotor gating without G protein adaptation after repeated D2
      like dopamine receptor agonist treatment in rats.
AB  - Sensorimotor gating, a neural process severely disrupted in patients with
      schizophrenia, can be measured by assessing prepulse inhibition (PPI) of acoustic
      startle responses. PPI is disrupted in experimental animals by stimulation of
      D(2)-like dopamine receptors in the nucleus accumbens (NAc). We examined the
      effect of repeated treatment with a selective dopamine D(2)-like receptor
      agonist, quinpirole, and characterized the molecular substrates of the resulting
      PPI adaptation. Animals were treated once daily for 10 or 28 consecutive days
      with quinpirole (0.0, 0.05, 0.1, or 0.3 mg/kg, s.c.), and the effect on PPI was
      assessed throughout the treatment period. PPI was reduced after acute quinpirole
      administration, but gradually increased with repeated treatment. Quinpirole
      induced PPI disruption was attenuated after 10 days of treatment at lower doses,
      but complete recovery was not apparent until the treatment period was extended to
      28 days. Since chronic drug exposure can alter the dopamine system, we sought to
      characterize the effects of repeated quinpirole treatment on G proteins coupled
      to D(2)-like receptors in the NAc. Guanosine 5'-O-(3-[(35)S]thiotriphosphate)
      ([(35)S]GTPgammaS) binding and Western blot analysis revealed that repeated
      quinpirole treatment had no effect on NAc D(2)-like receptor G protein function
      or G protein levels. These data indicate that repeated activation of D(2)-like
      receptors by quinpirole produces tolerance in the absence of receptor or G
      protein changes, suggesting that the locus of dopaminergic adaptation might be at
      the intracellular level.

PMID- 14593084
TI  - Characterization of mu opioid receptor binding and G protein coupling in rat
      hypothalamus, spinal cord, and primary afferent neurons during inflammatory pain.
AB  - Peripheral analgesic effects of opioids are pronounced under inflammatory
      conditions, e.g., arthritis; however, little is known about adaptive changes of
      micro opioid receptor binding and G protein coupling in the peripheral versus
      central nervous system. The present study investigated the effects of
      inflammation on mu opioid receptor (MOP receptor) binding and G protein coupling
      of supraspinal, spinal, and peripheral MOP receptors. In addition, MOP receptors
      were identified in immunohistochemical experiments in dorsal root ganglia (DRG)
      of inflamed and noninflamed rats. The number of MOP receptor binding sites
      decreased from hypothalamus (HT) > spinal cord (SC) > DRG. Unilateral Freund's
      complete adjuvant inflammation of one hindpaw induced a significant up-regulation
      of MOP receptor sites only in DRG but not in HT or SC. This up-regulation was
      time-dependent, restricted to the inflamed side, and showed a peak at 24 h. The
      full-agonist [D-Ala(2),N-MePhe(4),Gly(5)-ol]-enkephalin (DAMGO) induced MOP
      receptor G protein coupling with decreasing efficacies (E(max)) from HT > SC >
      DRG. Inflammation resulted in significant increases in MOP receptor G protein
      coupling only in membranes of DRG, but not in HT, SC, or DRG on the contralateral
      side of inflammation. This suggests that changes in MOP receptor levels are not
      related to systemically released mediators. These findings show that inflammation
      causes changes in MOP receptor binding and G protein coupling after DAMGO
      stimulation selectively in primary afferent neurons but did not cause any
      adaptive changes of MOP receptor in HT or SC.

PMID- 14593085
TI  - Pharmacodynamics of the type II calcimimetic compound cinacalcet HCl.
AB  - Calcimimetic compounds, which activate the parathyroid cell Ca(2+) receptor (CaR)
      and inhibit parathyroid hormone (PTH) secretion, are under experimental study as
      a treatment for hyperparathyroidism. This report describes the salient
      pharmacodynamic properties, using several test systems, of a new calcimimetic
      compound, cinacalcet HCl. Cinacalcet HCl increased the concentration of
      cytoplasmic Ca(2+) ([Ca(2+)](i)) in human embryonic kidney 293 cells expressing
      the human parathyroid CaR. Cinacalcet HCl (EC(50) = 51 nM) in the presence of 0.5
      mM extracellular Ca(2+) elicited increases in [Ca(2+)](i) in a dose- and calcium
      dependent manner. Similarly, in the presence of 0.5 mM extracellular Ca(2+),
      cinacalcet HCl (IC(50) = 28 nM) produced a concentration-dependent decrease in
      PTH secretion from cultured bovine parathyroid cells. Using rat medullary thyroid
      carcinoma 6-23 cells expressing the CaR, cinacalcet HCl (EC(50) = 34 nM) produced
      a concentration-dependent increase in calcitonin secretion. In vivo studies in
      rats demonstrated cinacalcet HCl is orally bioavailable and displays
      approximately linear pharmacokinetics over the dose range of 1 to 36 mg/kg.
      Furthermore, this compound suppressed serum PTH and blood-ionized Ca(2+) levels
      and increased serum calcitonin levels in a dose-dependent manner. Cinacalcet was
      about 30-fold more potent at lowering serum levels of PTH than it was at
      increasing serum calcitonin levels. The S-enantiomer of cinacalcet (S-AMG 073)
      was at least 75-fold less active in these assay systems. The present findings
      provide compelling evidence that cinacalcet HCl is a potent and stereoselective
      activator of the parathyroid CaR and, as such, might be beneficial in the
      treatment of hyperparathyroidism.

PMID- 14593086
TI  - Effect of a beta 2-adrenoceptor stimulation on hyperglycemia-induced endothelial
      dysfunction.
AB  - To investigate whether beta(2)-adrenoceptors exist on endothelial cells and
      whether a beta(2)-adrenoceptor stimulation might prevent the development of
      hyperglycemia-induced endothelial dysfunction, porcine aortic endothelial cells
      (PAECs) were cultured and chronically exposed to either 5 mM D-glucose
      ("normoglycemia") or 20 mM D-glucose ("hyperglycemia"), with or without 100 nM
      salbutamol in absence or presence of beta(2)-adrenoceptor antagonist ICI 118,551
      [1-[2,3-(dihydro-7-methyl-1H-inden-4-yl)oxyl]-3-[(1-methylethyl)-amino]-2
      butanol] or beta(1)-antagonist metoprolol. For osmotic control, PAECs were
      exposed to 15 mM L-glucose. We measured nitric oxide release using the met
      hemoglobin assay and assessed beta-adrenoceptor density and subtypes by
      radioligand binding. Furthermore, we determined intracellular NADH and NADPH
      using high-performance liquid chromatography. High D-glucose concentrations but
      not L-glucose led to significantly reduced basal and stimulated nitric oxide
      release. Chronic salbutamol treatment significantly antagonized the impairment of
      the nitric oxide response, which was inhibited by ICI 118,551 but not by
      metoprolol. The number of giant cells was significantly increased in
      hyperglycemia, which could be prevented by salbutamol. Binding of the radioligand
      (-)-[(125)I]iodocyanopindolol revealed a total beta-adrenoceptor density of 29.8
      +/- 3.7 (normoglycemic) and 30.3 +/- 3.6 (hyperglycemic) fmol/mg protein.
      Displacement by ICI 118,551 revealed beta-adrenoceptor subtype distribution with
      30.3 +/- 4.4 (normoglycemic) and 29.1 +/- 3.8% beta(2)-adrenoceptors. NADH
      production increased in hyperglycemia, which was completely prevented by
      salbutamol. We conclude that hyperglycemia in PAEC induces endothelial
      dysfunction with impaired nitric oxide release and that this can be prevented by
      beta(2)-adrenoceptor stimulation.

PMID- 14593087
TI  - Distinct molecular recognition of psychostimulants by human and Drosophila
      serotonin transporters.
AB  - In this study, human embryonic kidney (HEK)-293 cells stably expressing human,
      Drosophila, or a chimeric serotonin (5-hydroxytryptamine, 5-HT) transporter
      (hSERT, dSERT, and H(1-281)D(282-476)H(477-638), respectively) were used to
      explore the ability of two libraries of structurally distinct psychostimulants to
      inhibit 5-HT uptake. One library consisted of 3-phenyltropane analogs, whereas
      the second library consisted of several substituted amphetamines. hSERT exhibited
      a lower K(i) value for all the compounds in both libraries compared with dSERT,
      whereas the chimeric SERT exhibited properties more closely resembling those of
      dSERT. This species selectivity was explored using computer-generated comparative
      molecular field analysis to model the interactions of the cocaine analogs and
      substituted amphetamines at hSERT, dSERT, and the cross-species chimera. Models
      for the 3-phenyltropane analogs indicate that a region exists around the aromatic
      ring where decreased electron density is favored, particularly for hSERT. This
      finding may indicate pi-pi stacking with an aromatic amino acid residue in SERT.
      Also, electronegative substituents in the 4'-position provide favorable
      interactions. This structural feature was demonstrated by increased potency of
      analogs with electronegative substituents on the aromatic ring that withdraw
      electron density. For the substituted amphetamines, key areas for interaction
      exist around the amine, an electrostatic component surrounding the 3-position on
      the aromatic ring, and a steric component surrounding the 4-position.

PMID- 14593088
TI  - Continuous administration of organic nitrate decreases hepatic cytochrome P450.
AB  - We previously reported that cytochrome P450 (P450) is a key enzyme of organic
      nitrate biotransformation and that P450 levels of the heart and its vessels
      markedly decreased at the development of nitrate tolerance. Although our
      attention was mainly focused on the circulatory organs, most organic nitrates,
      including nitroglycerin (NTG), are metabolized in the liver, where nitric oxide
      (NO) is concomitantly produced from the organic nitrates. NO reacts with various
      molecules such as superoxide, heme, thiols, and oxygen. This paper examined
      whether hepatic P450 levels are also affected after organic nitrate
      administration, since the liver is the major organ of P450 related metabolism.
      Male Wistar rats were intravenously administrated NTG or isosorbide dinitrate
      (ISDN) for 24-96 h. We observed the level of hemeoxygenase-1 (HO-1) as the
      functional marker of hepatic P450, since one of the acute phase target proteins
      of NO induction is an inducible type of HO-1. Hepatic P450 was drastically
      decreased after 48 or 72 h of continuous NTG or ISDN infusion, when nitrate
      tolerance was observed, but it recovered 48 h after cessation of the NTG
      administration. HO-1 was induced within 24 h of continuous NTG infusion, but it
      returned to normal levels 48 h after cessation of NTG. The administration of
      sodium nitroprusside, an agent to which the animals showed no tolerance, did not
      induce HO-1 or P450 depletion. Chronic administration of organic nitrates
      significantly decreased hepatic P450. These results suggest that P450-dependent
      drug metabolism may be drastically affected after continuous organic nitrate
      administration.

PMID- 14593089
TI  - Rosiglitazone activates renal sodium- and water-reabsorptive pathways and lowers
      blood pressure in normal rats.
AB  - Synthetic agonists of the peroxisomal proliferator-activated receptor subtype
      gamma (PPAR-gamma) are highly beneficial in the treatment of type II diabetes.
      However, they are also associated with fluid retention and edema, potentially
      serious side effects of unknown origin. These studies were designed to test the
      hypothesis that rosiglitazone (RGZ, PPAR-gamma agonist) may activate sodium- and
      water-reabsorptive processes in the kidney, possibly in response to a drop in
      mean arterial blood pressure (MAP), as well as directly through PPAR-gamma.
      Targeted proteomics of the major renal sodium and water transporters and channel
      proteins was used to identify potentially regulated sites of renal sodium and
      water reabsorption. RGZ (47 or 94 mg/kg diet) was fed to male, Sprague-Dawley
      rats (approximately 270g) for 3 days. MAP, measured by radiotelemetry, was
      decreased significantly in rats fed either level of RGZ, relative to control
      rats. Delta MAP from baseline was -3.2 +/- 1.2 mm Hg in rats fed high-dose RGZ
      versus + 3.4 +/- 0.8 for rats fed control diet. RGZ did not affect feed or water
      intake, but rats treated with high-dose RGZ had decreased urine volume (by 22%),
      sodium excretion (44%), kidney weight (9%), and creatinine clearance (35%). RGZ
      increased whole kidney protein abundance of the alpha-1 subunit of Na-K-ATPase,
      the bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2), the sodium hydrogen
      exchanger (NHE3), the aquaporins 2 and 3, and endothelial nitric-oxide synthase.
      We conclude that both increases in renal tubule transporter abundance and a
      decrease in glomerular filtration rate likely contribute to the RGZ-induced
      sodium retention.

PMID- 14593090
TI  - Neuroactive steroid interactions with voltage-dependent anion channels: lack of
      relationship to GABA(A) receptor modulation and anesthesia.
AB  - Neuroactive steroids modulate the function of gamma-aminobutyric acid type A
      (GABA(A)) receptors in brain; this is the presumed basis of their action as
      anesthetics. In a previous study using the neuroactive steroid analog,
      (3alpha,5beta)-6-azi-3-hydroxypregnan-20-one (6-AziP), as a photoaffinity
      labeling reagent, we showed that voltage-dependent anion channel-1 (VDAC-1) was
      the predominant protein labeled in brain. Antisera to VDAC-1 were shown to
      coimmunoprecipitate GABA(A) receptors, suggesting a functional relationship
      between steroid binding to VDAC-1 and modulation of GABA(A) receptor function.
      This study examines the contribution of steroid binding to VDAC proteins to
      modulation of GABA(A) receptor function and anesthesia. Photolabeling of 35-kDa
      protein with [(3)H]6-AziP was reduced 85% in brain membranes prepared from VDAC-1
      deficient mice but was unaffected by deficiency of VDAC-3. The photolabeled 35
      kDa protein in membranes from VDAC-1-deficient mice was identified by two
      dimensional electrophoresis and electrospray ionization-tandem mass spectrometry
      as VDAC-2. The absence of VDAC-1 or VDAC-3 had no effect on the ability of
      neuroactive steroids to modulate GABA(A) receptor function as evidenced by
      radioligand ([(35)S] t-butylbicyclophosphorothionate) binding or by
      electrophysiological studies. Electrophysiological studies also showed that
      neuroactive steroids modulate GABA(A) receptor function normally in VDAC-2
      deficient fibroblasts transfected with alpha(1)beta(2)gamma(2) GABA(A) receptor
      subunits. Finally, the neuroactive steroid pregnanolone [(3alpha,5beta)-3
      hydroxypregnan-20-one] produced anesthesia (loss of righting reflex) in VDAC-1-
      and VDAC-3-deficient mice, and there was no difference in the recovery time
      between the VDAC-deficient mice and wild-type controls. These data indicate that
      neuroactive steroid binding to VDAC-1, -2, or -3 is unlikely to mediate GABA(A)
      receptor modulation or anesthesia.

PMID- 14593091
TI  - Anxiolytic-like effects of escitalopram, citalopram, and R-citalopram in
      maternally separated mouse pups.
AB  - The S-enantiomer of citalopram, escitalopram, is a selective serotonin reuptake
      inhibitor (SSRI) that appears to be responsible for citalopram's antidepressant
      and anxiolytic effects. Clinically, escitalopram is reported to have fewer
      adverse side effects than do other SSRIs. This study compared escitalopram to
      other antidepressants in a preclinical procedure predicting anxiolytic-like
      effects of drugs. Carworth Farms Webster (CFW) mouse pups (7 days old) were
      separated from the dam and maintained at a temperature of 34 degrees C. Forty
      five minutes after administering citalopram (0.56-10 mg/kg), escitalopram (0.0056
      3 mg/kg), R-citalopram (1-10 mg/kg), paroxetine (0.3-3 mg/kg), fluoxetine (1-30
      mg/kg), or venlafaxine (3-56 mg/kg) subcutaneously, the pups were placed
      individually on a 19.5 degrees C surface for 4 min. Ultrasonic vocalizations
      (USVs) (30-80 kHz), grid crossing, rolling (i.e., the pup turned on one side or
      its back), and colonic temperature were recorded. All the drugs reduced USV
      emission; escitalopram was the most potent (ED(50) 0.05 mg/kg), followed by
      paroxetine (0.17 mg/kg), citalopram (1.2 mg/kg), fluoxetine (4.3 mg/kg), R
      citalopram (6 mg/kg), and venlafaxine (7 mg/kg). The doses that decreased USVs
      differed from those that increased motor activity. Increased grid crossing
      occurred after low doses of paroxetine (0.03 or 0.1 mg/kg) and fluoxetine (1
      mg/kg), but only after the highest doses of the citalopram enantiomers and
      venlafaxine (0.3, 10, and 56 mg/kg, respectively). Except for escitalopram and
      venlafaxine, high doses of the treatments increased rolling. R-Citalopram caused
      a 10-fold rightward shift in escitalopram's dose-effect curve, suggesting that R
      citalopram inhibits escitalopram's anxiolytic-like effects. These data support
      clinical findings that escitalopram is a potent, well tolerated SSRI with
      anxiolytic-like effects.

PMID- 14593092
TI  - Stimulation of extracellular signal-regulated kinase pathway by suramin with
      concomitant activation of DNA synthesis in cultured cells.
AB  - Suramin is a well known antitrypanosomal drug and a novel experimental agent for
      the treatment of several cancers, yet the molecular mechanisms through which
      suramin exerts its effects on cell functions are not completely clear. In this
      study, we investigated the potential of suramin to activate the mitogen-activated
      protein kinase cascade in cultured Chinese hamster ovary (CHO) cells. The
      treatment of CHO cells with suramin increased the enzyme activity of
      extracellular signal-regulated kinases (ERK1/2) approximately 10-fold dose and
      time dependently. The EC(50) value was approximately 2.4 microM. This activation
      is inhibited by PD98059 and wortmannin/LY294002, indicating a crucial role for
      mitogen-activated protein kinase kinase (MEK) and phosphatidylinositol 3-kinase
      (PI3K), respectively. Suramin-mediated stimulation of PI3K was confirmed by the
      observation that suramin stimulates the phosphorylation of protein kinase B (Akt)
      in a wortmannin-sensitive manner. Furthermore, cAMP response element-binding
      protein, a transcription factor, was also activated by suramin in a MEK-dependent
      manner. The suramin-induced phosphorylation of cGMP-dependent protein kinase was
      also suggested by a solid-phase kinase assay. The suramin effects on CHO cells
      were shown to have a concomitant increase in DNA synthesis, which was attenuated
      by PD98059. Similar activation of ERK1/2 activity by suramin was observed in
      other cell lines such as Chinese hamster lung or PC12 cells, but not in RBL2H3,
      ECV304, and OVK18 cells, indicating a cell-type specific mechanism for suramin.
      These results indicate that suramin induces mitogenic activity in several cell
      lines through the pathway from PI3K to MEK and ERK.

PMID- 14593093
TI  - Activation of the ERK1/2 and p38 mitogen-activated protein kinase pathways
      mediates fibroblast growth factor-induced growth arrest of chondrocytes.
AB  - Fibroblast growth factors (FGFs) regulate long bone development by affecting the
      proliferation and differentiation of chondrocytes. FGF treatment inhibits the
      proliferation of chondrocytes both in vitro and in vivo, but the signaling
      pathways involved have not been clearly identified. In this report we show that
      both the MEK-ERK1/2 and p38 MAPK pathways, but not phospholipase C gamma or
      phosphatidylinositol 3-kinase, play a role in FGF-mediated growth arrest of
      chondrocytes. Chemical inhibitors of the MEK1/2 or the p38 MAPK pathways applied
      to rat chondrosarcoma (RCS) chondrocytes significantly prevented FGF-induced
      growth arrest. The retinoblastoma family members p107 and p130 were previously
      shown to be essential effectors of FGF-induced growth arrest in chondrocytes. The
      dephosphorylation of p107, one of the earliest events in RCS growth arrest, was
      significantly blocked by MEK1/2 inhibitors but not by the p38 MAPK inhibitors,
      whereas that of p130, which occurs later, was partially prevented both by the MEK
      and p38 inhibitors. Furthermore, by expressing the nerve growth factor (NGF)
      receptor, TrkA, and the epidermal growth factor (EGF) receptor, ErbB1, in RCS
      cells we show that NGF treatment of the transfected cells caused growth
      inhibition, whereas EGF did not. FGF- and NGF-induced growth inhibition is
      accompanied by a strong and sustained activation of ERK1/2 and p38 MAPK and a
      decrease of AKT phosphorylation, whereas EGF induces a much more transient
      activation of p38 and ERK1/2 and increases AKT phosphorylation. These results
      indicate that inhibition of chondrocyte proliferation by FGF requires both ERK1/2
      and p38 MAPK signaling and also suggest that sustained activation of these
      pathways is required to achieve growth inhibition.

PMID- 14593094
TI  - Spatial approximation between the amino terminus of a peptide agonist and the top
      of the sixth transmembrane segment of the secretin receptor.
AB  - Distinct spatial approximations between residues within the secretin
      pharmacophore and its receptor can provide important constraints for modeling
      this agonist-receptor complex. We previously used a series of probes
      incorporating photolabile residues into positions 6, 12, 13, 14, 18, 22, and 26
      of the 27-residue peptide and demonstrated that each covalently labeled a site
      within the receptor amino terminus. Although supporting a critical role of this
      domain for ligand binding, it does not explain the molecular mechanism of
      receptor activation. Here, we developed probes having photolabile residues at the
      amino terminus of secretin to explore possible approximations with a different
      receptor domain. The first probe incorporated a photolabile p-benzoyl-l
      phenylalanine into the position of His(1) of rat secretin
      ([Bpa(1),Tyr(10)]secretin-27). Because His(1) is critical for function, we also
      positioned a photolabile Bpa as an amino-terminal extension, in positions -1 (rat
      [Bpa(-1),Tyr(10)]secretin-27) and -2 (rat [Bpa(-2),Gly(-1),Tyr(10)]secretin-27).
      Each analog was shown to be a full agonist, stimulating cAMP accumulation in
      receptor-bearing Chinese hamster ovary-SecR cells in a concentration-dependent
      manner, with the position -2 probe being most potent. They bound specifically and
      saturably, although the position 1 analog had lowest affinity, and all were able
      to label the receptor efficiently. Sequential specific cleavage, purification,
      and sequencing demonstrated that the sites of covalent attachment for each probe
      were high within the sixth transmembrane segment. This suggests that secretin
      binding may exert tension between the receptor amino terminus and the
      transmembrane domain to elicit a conformational change effecting receptor
      activation.

PMID- 14593095
TI  - Protein export across the inner membrane of mitochondria: the nature of
      translocated domains determines the dependence on the Oxa1 translocase.
AB  - The biogenesis of mitochondria requires the insertion of both nuclear and
      mitochondrially encoded proteins into the inner membrane. The inner membrane
      protein Oxa1 plays an important role in this process. Translocation of the
      terminal intermembrane space domains of subunit 2 of the cytochrome oxidase
      complex, Cox2, strictly depends on Oxa1. In contrast, other Oxa1 substrates can
      be inserted independently of Oxa1 function, although at reduced efficiency. A
      Saccharomyces cerevisiae mutant containing a large deletion in its mitochondrial
      genome allowed us to analyze the insertion process of a fusion protein of
      cytochrome b and Cox2. In this mutant, the N-terminal domain of Cox2 is
      synthesized as a hairpin loop that is flanked by hydrophobic transmembrane
      segments on both sides. Both genetic and biochemical evidences indicate that
      translocation of this region across the inner membrane still requires Oxa1
      function. Thus, the position of intermembrane space domains within protein
      sequences does not appear to determine their dependence on the Oxa1 translocase.
      Our observations rather suggest that the dependence on Oxa1 correlates with the
      net charge of the domain that has to be translocated across the lipid bilayer.

PMID- 14593096
TI  - Membrane topology and nicastrin-enhanced endoproteolysis of APH-1, a component of
      the gamma-secretase complex.
AB  - APH-1, presenilin, nicastrin, and Pen-2 are proteins with varying membrane
      topologies that compose the gamma-secretase complex, which is responsible for the
      intramembrane proteolysis of several substrates including the amyloid precursor
      protein. APH-1 is known to be necessary for gamma-secretase activity, but its
      precise function in the complex is not fully understood, and its membrane
      topology has not been described, although it is predicted to traverse the
      membrane seven times. To investigate this, we used selective permeabilization of
      the plasma membrane and immunofluorescence microscopy to show that the C terminus
      of the APH-1 resides in the cytosolic space. Insertion of N-linked glycosylation
      sites into each of the hydrophilic loop domains and the N terminus of APH-1
      showed that the N-terminal domain as well as loops 2, 4, and 6 could be
      glycosylated, whereas loops 1, 3, and 5 were not. Thus, APH-1 topologically
      resembles a seven-transmembrane domain receptor with the N terminus and even
      numbered loops facing the endoplasmic reticulum lumen, and the C terminus and odd
      numbered loops reside in the cytosolic space. By using these glycosylation
      mutants, we provide evidence that the association between nicastrin and APH-1 may
      occur very soon after APH-1 synthesis and that the interaction between these two
      proteins may rely more heavily on the transmembrane domains of APH-1 than on the
      loop domains. Furthermore, we found that APH-1 can be processed by several
      endoproteolytic events. One of these cleavages is strongly up-regulated by co
      expression of nicastrin and generates a stable C-terminal fragment that
      associates with nicastrin.

PMID- 14593097
TI  - Localization of low density lipoprotein receptor-related protein 1 to caveolae in
      3T3-L1 adipocytes in response to insulin treatment.
AB  - The insulin-induced translocation of low density lipoprotein receptor-related
      protein 1 (LRP1) from intracellular membranes to the cell surface in 3T3-L1
      adipocytes was differentiation-dependent and did not occur in 3T3-L1 fibroblasts.
      Prompted by findings that the plasma membrane of 3T3-L1 adipocytes was rich in
      caveolae, we determined whether LRP1 became caveolae-associated upon insulin
      stimulation. The caveolae domain was isolated by the well characterized detergent
      solubilization and sucrose density ultracentrifugation methodology. Under basal
      conditions, only a trace amount of LRP1 was caveolae-associated despite the
      markedly elevated caveolin-1 and caveolae after adipocytic cell differentiation.
      Upon insulin treatment, the amount of LRP1 associated with caveolae was increased
      by 4-fold within 10 min, which was blocked completely by pretreatment with
      wortmannin prior to insulin. The caveolar localization of LRP1 in adipocytes was
      specific to insulin; treatment with platelet-derived growth factor-bb isoform did
      not promote but rather decreased caveolar localization of LRP1 below basal
      levels. The insulin-induced caveolar localization of LRP1 was also observed in
      3T3-L1 fibroblasts where translocation of LRP1 from intracellular membranes to
      the cell surface was absent, suggesting that association of LRP1 with caveolae
      was achieved, at least in part, through lateral transmigration along the plane of
      plasma membranes. Immunocytochemistry studies revealed partial co-localization of
      LRP1 (either endogenous LRP1 or an epitope-tagged minireceptor) with caveolin-1
      in cells treated with insulin, which was confirmed by co-immunoprecipitation of
      LRP1 with caveolin-1 in cells treated with insulin but not platelet-derived
      growth factor-bb. These results suggest that the localization of LRP1 to caveolae
      responds selectively to extracellular signals.

PMID- 14593098
TI  - Involvement of DnaE, the second replicative DNA polymerase from Bacillus
      subtilis, in DNA mutagenesis.
AB  - In a large group of organisms including low G + C bacteria and eukaryotic cells,
      DNA synthesis at the replication fork strictly requires two distinct replicative
      DNA polymerases. These are designated pol C and DnaE in Bacillus subtilis. We
      recently proposed that DnaE might be preferentially involved in lagging strand
      synthesis, whereas pol C would mainly carry out leading strand synthesis. The
      biochemical analysis of DnaE reported here is consistent with its postulated
      function, as it is a highly potent enzyme, replicating as fast as 240
      nucleotides/s, and stalling for more than 30 s when encountering annealed 5'-DNA
      end. DnaE is devoid of 3' --> 5'-proofreading exonuclease activity and has a low
      processivity (1-75 nucleotides), suggesting that it requires additional factors
      to fulfill its role in replication. Interestingly, we found that (i) DnaE is SOS
      inducible; (ii) variation in DnaE or pol C concentration has no effect on
      spontaneous mutagenesis; (iii) depletion of pol C or DnaE prevents UV-induced
      mutagenesis; and (iv) purified DnaE has a rather relaxed active site as it can
      bypass lesions that generally block other replicative polymerases. These results
      suggest that DnaE and possibly pol C have a function in DNA repair/mutagenesis,
      in addition to their role in DNA replication.

PMID- 14593099
TI  - Glycosylation is important for cell surface expression of the water channel
      aquaporin-2 but is not essential for tetramerization in the endoplasmic
      reticulum.
AB  - Aquaporin-2 (AQP2) is a pore-forming protein that is required for regulated
      reabsorption of water from urine. Mutations in AQP2 lead to nephrogenic diabetes
      insipidus, a disorder in which functional AQP2 is not expressed on the apical
      cell surface of kidney collecting duct principal cells. The mechanisms and
      pathways directing AQP2 from the endoplasmic reticulum to the Golgi complex and
      beyond have not been defined. We found that approximately 25% of newly
      synthesized AQP2 is glycosylated. Nonglycosylated and complex-glycosylated wild
      type AQP2 are stable proteins with a half-life of 6-12 h and are both detectable
      on the cell surface. We show that AQP2 forms tetramers in the endoplasmic
      reticulum during or very early after synthesis and reaches the Golgi complex in 1
      1.5 h. We also report that glycosylation is neither essential for tetramerization
      nor for transport from the endoplasmic reticulum to the Golgi complex. Instead,
      the N-linked glycan is important for exit from the Golgi complex and sorting of
      AQP2 to the plasma membrane. These results are important for understanding the
      molecular mechanisms responsible for the intracellular retention of AQP2 in
      nephrogenic diabetes insipidus.

PMID- 14593100
TI  - Monoclonal antibody against a peptide of human prion protein discriminates
      between Creutzfeldt-Jacob's disease-affected and normal brain tissue.
AB  - Current methods for diagnosing transmissible spongiform encephalopathies rely on
      the degradation of the cellular prion protein (PrP(C)) and the subsequent
      detection of the protease-resistant remnant of the pathological prion isoform
      PrP(Sc) by antibodies that react with all forms of PrP. We report on a monoclonal
      antibody, V5B2, raised against a peptide from the C-terminal part of PrP, which
      recognizes an epitope specific to PrP(Sc). In cryostat sections from Creutzfeldt
      Jacob's disease (CJD) patients' brains, V5B2 selectively labels various deposits
      of PrP(Sc) without any pretreatment for removal of PrP(C). V5B2 does not bind to
      non-CJD brain samples or to recombinant PrP, either in its native or denatured
      form. Specificity for PrP is confirmed by a sandwich enzyme-linked immunosorbent
      assay utilizing V5B2, which discriminates between CJD and normal samples without
      proteinase K treatment, and by immunoprecipitation from CJD brain homogenate. The
      PrP(Sc)-specific epitope is disrupted by denaturation. We conclude that the C
      terminal part of PrP in disease-associated PrP(Sc) aggregates forms a structural
      epitope whose conformation is distinct from that of PrP(C).

PMID- 14593101
TI  - Core 2 branching beta1,6-N-acetylglucosaminyltransferase and high endothelial
      venule-restricted sulfotransferase collaboratively control lymphocyte homing.
AB  - L-selectin mediates lymphocyte homing by facilitating lymphocyte adhesion to
      carbohydrate ligands expressed on high endothelial venules (HEV) of the secondary
      lymphoid organs. Previous studies demonstrated that L-selectin ligand
      sulfotransferase (LSST) forms 6-sulfo sialyl Lewis x (sLe(x)) on both core 2
      branch and MECA-79-positive extended core 1 O-glycans, but the chemical nature
      and roles of HEV ligands elaborated by LSST and core 2 beta1,6-N
      acetylglucosaminyltransferase-1 (Core2GlcNAcT) have been undefined. In the
      present study, we have generated mutant mice with deficient LSST and show that
      inactivation of LSST gene alone leads to only partial impairment of lymphocyte
      homing to peripheral lymph nodes and moderate reduction in lymphocyte counts in
      the peripheral lymph nodes, despite the fact that L-selectin ligands that contain
      6-sulfo sLe(x) are reduced at HEV. By contrast, LSST/Core2GlcNAcT double null
      mice exhibited a markedly reduced lymphocyte homing and reduced lymphocyte counts
      as a result of significantly decreased 6-sulfo sLe(x) on HEV L-selectin
      counterreceptors, relative to LSST- or Core2GlcNAcT-single null mice. Moreover,
      induction of LSST and Core2GlcNAcT transcripts was observed in HEV-like structure
      formed in the salivary gland of the non-obese diabetic mouse, which displays
      chronic inflammation. These results indicate that LSST and Core2GlcNAcT
      cooperatively synthesize HEV-specific L-selectin ligands required for lymphocyte
      homing and suggest that LSST and Core2GlcNAcT play a critical role in lymphocyte
      trafficking during chronic inflammation.

PMID- 14593102
TI  - Role of CREB in transcriptional regulation of CCAAT/enhancer-binding protein beta
      gene during adipogenesis.
AB  - The proximal promoter of the C/EBPbeta gene possesses dual cis regulatory
      elements (TGA1 and TGA2), both of which contain core CREB binding sites.
      Comparison of the activities of C/EBPbeta promoter-reporter genes with 5'
      truncations or site-directed mutations in the TGA elements showed that both are
      required for maximal promoter function. Electrophoretic mobility shift and
      chromatin immunoprecipitation (ChIP) analyses with antibodies specific to CREB
      and ATF1 showed that these CREB family members associate with the proximal
      promoter both in vitro and ex vivo. Immunoblotting and ChIP analysis revealed
      that other CREB family members, CREM and ATF1, are up-regulated and associate
      with the proximal C/EBPbeta promoter in mouse embryonic fibroblasts (MEFs) from
      CREB(-/-) mice. ChIP analysis of wild-type MEFs and 3T3-L1 preadipocytes revealed
      that interaction of phospho-CREB, the active form of CREB, with the C/EBPbeta
      gene promoter occurs only after induction of differentiation of 3T3-L1
      preadipocytes and MEFs. Consistent with the interaction of CREB and ATF1 at the
      TGA regulatory elements, expression of constitutively active CREB strongly
      activated C/EBPbeta promoter-reporter genes, induced expression of endogenous
      C/EBPbeta, and caused adipogenesis in the absence of the hormonal inducers
      normally required. Conversely, expression of a dominant-negative CREB blocked
      promoter-reporter activity, expression of C/EBPbeta, and adipogenesis. When
      subjected to the standard adipocyte differentiation protocol, wild-type MEFs
      differentiate into adipocytes at high frequency, whereas CREB(-/-) MEFs exhibit
      greatly reduced expression of C/EBPbeta and differentiation. The low level of
      expression of C/EBPbeta and differentiation in CREB(-/-) MEFs appears to be due
      to up-regulation of other CREB protein family members, i.e. ATF1 and CREM.

PMID- 14593103
TI  - Protein splicing of inteins with atypical glutamine and aspartate C-terminal
      residues.
AB  - Inteins are protein-splicing domains present in many proteins. They self-catalyze
      their excision from the host protein, ligating their former flanks by a peptide
      bond. The C-terminal residue of inteins is typically an asparagine (Asn).
      Cyclization of this residue to succinimide causes the final detachment of inteins
      from their hosts. We studied protein-splicing activity of two inteins with
      atypical C-terminal residues. One having a C-terminal glutamine (Gln), isolated
      from Chilo iridescent virus (CIV), and another unique intein, first reported
      here, with a C-terminal aspartate, isolated from Carboxydothermus
      hydrogenoformans (Chy). Protein-splicing activity was examined in the wild-type
      inteins and in several mutants with N- and C-terminal amino acid substitutions.
      We demonstrate that both wild-type inteins can protein splice, probably by new
      variations of the typical protein-splicing mechanism. Substituting the atypical C
      terminal residue to the typical Asn retained protein-splicing only in the CIV
      intein. All diverse C-terminal substitutions in the Chy intein (Asp(345) to Asn,
      Gln, Glu, and Ala) abolished protein-splicing and generated N- and C-terminal
      cleavage. The observed C-terminal cleavage in the Chy intein ending with Ala
      cannot be explained by cyclization of this residue. We present and discuss
      several new models for reactions in the protein-splicing pathway.

PMID- 14593104
TI  - The predicted TM10 transmembrane sequence of the cardiac Ca2+ release channel
      (ryanodine receptor) is crucial for channel activation and gating.
AB  - The predicted TM10 transmembrane sequence, (4844)IIFDITFFFFVIVILLAIIQGLII(4867),
      has been proposed to be the pore inner helix of the ryanodine receptor (RyR) and
      to play a crucial role in channel activation and gating, as with the inner helix
      of bacterial potassium channels. However, experimental evidence for the
      involvement of the TM10 sequence in RyR channel activation and gating is lacking.
      In the present study, we have systematically investigated the effects of
      mutations of each residue within the 24-amino acid TM10 sequence of the mouse
      cardiac ryanodine receptor (RyR2) on channel activation by caffeine and Ca(2+).
      Intracellular Ca(2+) release measurements in human embryonic kidney 293 cells
      expressing the RyR2 wild type and TM10 mutants revealed that several mutations in
      the TM10 sequence either abolished caffeine response or markedly reduced the
      sensitivity of the RyR2 channel to activation by caffeine. By assessing the
      Ca(2+) dependence of [(3)H]ryanodine binding to RyR2 wild type and TM10 mutants
      we also found that mutations in the TM10 sequence altered the sensitivity of the
      channel to activation by Ca(2+) and enhanced the basal activity of
      [(3)H]ryanodine binding. Furthermore, single I4862A mutant channels exhibited
      considerable channel openings and altered gating at very low concentrations of
      Ca(2+). Our data indicate that the TM10 sequence constitutes an essential
      determinant for channel activation and gating, in keeping with the proposed role
      of TM10 as an inner helix of RyR. Our results also shed insight into the
      orientation of the TM10 helix within the RyR channel pore.

PMID- 14593105
TI  - Interleukin 1 activates STAT3/nuclear factor-kappaB cross-talk via a unique TRAF6
      and p65-dependent mechanism.
AB  - Interleukins (IL) 1 and 6 are important cytokines that function via the
      activation, respectively, of the transcription factors NF-kappaB and STAT3. We
      have observed that a specific type of kappa B DNA sequence motif supports both NF
      kappaB p65 homodimer binding and cooperativity with non-tyrosine-phosphorylated
      STAT3. This activity, in contrast to that mediated by kappaB DNA motifs that do
      not efficiently bind p65 homodimers, is shown to be uniquely dependent upon
      signal transduction through the carboxyl terminus of TRAF6. Furthermore, STAT3
      and p65 are shown to physically interact, in vivo, and this interaction appears
      to inhibit the function of "classical" STAT3 GAS-like binding sites. The distinct
      p50 form of NF-kappaB is also shown to interact with STAT3. However, in contrast
      to p65, p50 cooperates with STAT3 bound to GAS sites. These data argue for a
      novel transcription factor cross-talk mechanism that may help resolve
      inconsistencies previously reported regarding the mechanism of IL-1 inhibition of
      IL-6 activity during the acute-phase response.

PMID- 14593106
TI  - The DNA-binding domain of human papillomavirus type 18 E1. Crystal structure,
      dimerization, and DNA binding.
AB  - High risk types of human papillomavirus, such as type 18 (HPV-18), cause cervical
      carcinoma, one of the most frequent causes of cancer death in women worldwide.
      DNA replication is one of the central processes in viral maintenance, and the
      machinery involved is an excellent target for the design of antiviral therapy.
      The papillomaviral DNA replication initiation protein E1 has origin recognition
      and ATP-dependent DNA melting and helicase activities, and it consists of a DNA
      binding domain and an ATPase/helicase domain. While monomeric in solution, E1
      binds DNA as a dimer. Dimerization occurs via an interaction of hydrophobic
      residues on a single alpha-helix of each monomer. Here we present the crystal
      structure of the monomeric HPV-18 E1 DNA-binding domain refined to 1.8-A
      resolution. The structure reveals that the dimerization helix is significantly
      different from that of bovine papillomavirus type 1 (BPV-1). However, we
      demonstrate that the analogous residues required for E1 dimerization in BPV-1 and
      the low risk HPV-11 are also required for HPV-18 E1. We also present evidence
      that the HPV-18 E1 DNA-binding domain does not share the same nucleotide and
      amino acid requirements for specific DNA recognition as BPV-1 and HPV-11 E1.

PMID- 14593107
TI  - alpha1-Proteinase inhibitor forms initial non-covalent and final covalent
      complexes with elastase analogously to other serpin-proteinase pairs, suggesting
      a common mechanism of inhibition.
AB  - Despite several concordant structural studies on the initial non-covalent complex
      that serpins form with target proteinases, a recent study on the non-covalent
      complex between the serpin alpha(1)-proteinase inhibitor (alpha(1)PI) and
      anhydroelastase concluded that translocation of the proteinase precedes cleavage
      of the reactive center loop and formation of the acyl ester. Because this
      conclusion is diametrically opposite to those of the other structural studies on
      serpin-proteinase pairs, we proceeded to examine this specific serpin-proteinase
      complex by the same successful NMR approach used previously on the alpha(1)PI
      Pittsburgh-S195A trypsin pair. Both non-covalent complex with anhydroelastase and
      covalent complex with active elastase were made with (15)N-alanine-labeled wild
      type alpha(1)PI. The heteronuclear single quantum correlation spectroscopy (HSQC)
      NMR spectrum of the non-covalent complex showed that the entire reactive center
      loop remained exposed, and the serpin body maintained a conformation
      indistinguishable from that of native alpha(1)PI, indicating no movement of the
      proteinase and no insertion of the reactive center loop into beta-sheet A. In
      contrast, the HSQC NMR spectrum of the covalent complex showed that the reactive
      center loop had fully inserted into beta-sheet A, indicating that translocation
      of the proteinase had occurred. These results agree with previous NMR,
      fluorescence resonance energy transfer, and x-ray crystallographic studies and
      suggest that a common mechanism is employed in formation of serpin-proteinase
      complexes. We found that preparations of anhydroelastase that are not
      appropriately purified contain material that can regenerate active elastase over
      time. It is likely that the material used by Mellet and Bieth contained such
      active elastase, resulting in mistaken attribution of the behavior of covalent
      complex to that of the non-covalent complex.

PMID- 14593108
TI  - Plasma membrane-cytoskeleton-endoplasmic reticulum complexes in neurons and
      astrocytes.
AB  - The possibility that certain integral plasma membrane (PM) proteins involved in
      Ca(2+) homeostasis form junctional units with adjacent endoplasmic reticulum (ER)
      in neurons and glia was explored using immunoprecipitation and
      immunocytochemistry. Rat brain membranes were solubilized with the mild, non
      ionic detergent, IGEPAL CA-630. Na(+)/Ca(2+) exchanger type 1 (NCX1), a key PM
      Ca(2+) transporter, was immunoprecipitated from the detergent-soluble fraction.
      Several abundant PM proteins co-immunoprecipitated with NCX1, including the
      alpha2 and alpha3 isoforms of the Na(+) pump catalytic (alpha) subunit, and the
      alpha2 subunit of the dihydropyridine receptor. The adaptor protein, ankyrin 2
      (Ank 2), and the cytoskeletal proteins, alpha-fodrin and beta-spectrin, also
      selectively co-immunoprecipitated with NCX1, as did the ER proteins, Ca(2+) pump
      type 2 (SERCA 2), and inositol-trisphosphate receptor type 1 (IP(3)R-1). In
      contrast, a number of other abundant PMs, adaptors, and cytoskeletal proteins did
      not co-immunoprecipitate with NCX1, including the Na(+) pump alpha1 isoform, PM
      Ca(2+) pump type 1 (PMCA1), beta-fodrin, and Ank 3. In reciprocal experiments,
      immunoprecipitation with antibodies to the Na(+) pump alpha2 and alpha3 isoforms,
      but not alpha1, co-immunoprecipitated NCX1; the antibodies to alpha1 did,
      however, co-immunoprecipitate PMCA1. Antibodies to Ank 2, alpha-fodrin, beta
      spectrin and IP(3)R-1 all co-immunoprecipitated NCX1. Immunocytochemistry
      revealed partial co-localization of beta-spectrin with NCX1, Na(+) pump alpha3,
      and IP(3)R-1 in neurons and of alpha-fodrin with NCX1 and SERCA2 in astrocytes.
      The data support the idea that in neurons and glia PM microdomains containing
      NCX1 and Na(+) pumps with alpha2 or alpha3 subunits form Ca(2+) signaling
      complexes with underlying ER containing SERCA2 and IP(3)R-1. These PM and ER
      components appear to be linked through the cytoskeletal spectrin network, to
      which they are probably tethered by Ank 2.

PMID- 14593109
TI  - Deubiquitination, a new player in Golgi to endoplasmic reticulum retrograde
      transport.
AB  - Modification by ubiquitin plays a major role in a broad array of cellular
      functions. Although reversal of this process, deubiquitination, likely represents
      an important regulatory step contributing to cellular homeostasis, functions of
      deubiquitination enzymes still remain poorly characterized. We have previously
      shown that the ubiquitin protease Ubp3p requires a co-factor, Bre5p, to
      specifically deubiquitinate the coat protein complex II (COPII) subunit Sec23p,
      which is involved in anterograde transport between endoplasmic reticulum and
      Golgi compartments. In the present report, we show that disruption of BRE5 gene
      also led to a defect in the retrograde transport from the Golgi to the
      endoplasmic reticulum. Further analysis indicate that the COPI subunit beta'-COP
      represents another substrate of the Ubp3p.Bre5p complex. All together, our
      results indicate that the Ubp3p.Bre5p deubiquitination complex co-regulates
      anterograde and retrograde transports between endoplasmic reticulum and Golgi
      compartments.

PMID- 14593110
TI  - Phosphorylation of Ser640 in muscle glycogen synthase by DYRK family protein
      kinases.
AB  - Glycogen synthase, a key enzyme in the regulation of glycogen synthesis by
      insulin, is controlled by multisite phosphorylation. Glycogen synthase kinase-3
      (GSK-3) phosphorylates four serine residues in the COOH terminus of glycogen
      synthase. Phosphorylation of one of these residues, Ser(640) (site 3a), causes
      strong inactivation of glycogen synthase. In previous work, we demonstrated in
      cell models that site 3a can be phosphorylated by an as yet unidentified protein
      kinase (3a-kinase) distinct from GSK-3. In the present study, we purified the 3a
      kinase from rabbit skeletal muscle and identified one constituent polypeptide as
      HAN11, a WD40 domain protein with unknown function. Another polypeptide was
      identified as DYRK1A, a member of the dual-specificity tyrosine phosphorylated
      and regulated protein kinase (DYRK) family. Two isoforms of DYRK, DYRK1A and
      DYRK1B, co-immunoprecipitate with HAN11 when coexpressed in COS cells indicating
      that the proteins interact in mammalian cells. Co-expression of DYRK1A, DYRK1B,
      or DYRK2 with a series of glycogen synthase mutants with Ser/Ala substitutions at
      the phosphorylation sites in COS cells revealed that protein kinases cause
      phosphorylation of site 3a in glycogen synthase. To confirm that DYRKs directly
      phosphorylate glycogen synthase, recombinant DYRK1A, DYRK2, and glycogen synthase
      were produced in bacterial cells. In the presence of Mg-ATP, both DYRKs
      inactivated glycogen synthase by more than 10-fold. The inactivation correlated
      with phosphorylation of site 3a in glycogen synthase. These results indicate that
      protein kinase(s) from the DYRK family may be involved in a new mechanism for the
      regulation of glycogen synthesis.

PMID- 14593111
TI  - Conserved high affinity ligand binding and membrane association in the native and
      refolded extracellular domain of the human glycine receptor alpha1-subunit.
AB  - The strychnine-sensitive glycine receptor (GlyR) is a ligand-gated chloride
      channel composed of ligand binding alpha- and gephyrin anchoring beta-subunits.
      To identify the secondary and quaternary structures of extramembraneous receptor
      domains, the N-terminal extracellular domain (alpha1-(1-219)) and the large
      intracellular TM3-4 loop (alpha1-(309-392)) of the human GlyR alpha1-subunit were
      individually expressed in HEK293 cells and in Escherichia coli. The extracellular
      domain obtained from E. coli expression was purified in its denatured form and
      refolding conditions were established. Circular dichroism and Fourier-transform
      infrared spectroscopy suggested approximately 25% alpha-helix and approximately
      48% beta-sheet for the extracellular domain, while no alpha-helices were
      detectable for the TM3-4 loop. Size exclusion chromatography and sucrose density
      centrifugation indicated that isolated glycine receptor domains assembled into
      multimers of distinct molecular weight. For the extracellular domain from E.
      coli, we found an apparent molecular weight compatible with a 15mer by gel
      filtration. The N-terminal domain from HEK293 cells, analyzed by sucrose gradient
      centrifugation, showed a bimodal distribution, suggesting oligomerization of
      approximately 5 and 15 subunits. Likewise, for the intracellular domain from E.
      coli, a single molecular mass peak of approximately 49 kDa indicated
      oligomerization in a defined native structure. As shown by [(3)H]strychnine
      binding, expression in HEK293 cells and refolding of the isolated extracellular
      domain reconstituted high affinity antagonist binding. Cell fractionation,
      alkaline extraction experiments, and immunocytochemistry showed a tight plasma
      membrane association of the isolated GlyR N-terminal protein. These findings
      indicate that distinct functional characteristics of the full-length GlyR are
      retained in the isolated N-terminal domain.

PMID- 14593112
TI  - Cloning and characterization of a gene expressed during terminal differentiation
      that encodes a novel inhibitor of growth.
AB  - We report here the cloning and initial characterization of a novel growth-related
      gene (EEG-1) that is located on the short arm of chromosome 12. Two spliced
      transcripts were cloned from human bone marrow and human erythroid progenitor
      cells: EEG-1L containing a 4350-nucleotide open reading frame encoding a putative
      protein of 1077 amino acids including a C1q-like globular domain, and an
      alternatively spliced transcript lacking exon 5 (EEG-1S) encodes a significantly
      smaller coding region and no C1q-like domain. Quantitative PCR revealed
      expression of both EEG-1 transcripts in all analyzed tissues. Plasmids encoding
      green fluorescent protein-tagged genes (GFP-EEG-1) were transfected into Chinese
      hamster ovary cells for localization and functional assays. In contrast to the
      diffuse cellular localization of the GFP control, GFP-EEG-1L was detected
      throughout the cytoplasm and excluded from the nucleus, and GFP-EEG-1S co
      localized with aggregated mitochondria. Transfection of both isoforms was
      associated with significantly increased levels of apoptosis. Stable transfection
      assays additionally demonstrated decreased growth in those cells expressing EEG-1
      at higher levels. Quantitative PCR analyses of mRNA obtained from differentiating
      erythroid cells from blood donors were performed to determine the transcriptional
      pattern of EEG-1 during erythropoiesis. EEG-1 expression was highly regulated
      with increased expression at the stage of differentiation associated with the
      onset of global nuclear condensation and reduced cell proliferation. We propose
      that the regulated expression of EEG-1 is involved in the orchestrated regulation
      of growth that occurs as erythroblasts shift from a highly proliferative state
      toward their terminal phase of differentiation.

PMID- 14593113
TI  - The mitogenic action of insulin-like growth factor I in normal human mammary
      epithelial cells requires the epidermal growth factor receptor tyrosine kinase.
AB  - The signals used by insulin-like growth factor I (IGF-I) to stimulate
      proliferation in human mammary epithelial cells have been investigated. IGF-I
      caused the activation of both ERKs and Akt. Activation of ERKs was slower and
      more transient than that of Akt. ZD1839, a specific epidermal growth factor
      receptor (EGFR) tyrosine kinase inhibitor, prevented activation of ERKs but not
      Akt by IGF-I. Inhibition of the EGFR with function-blocking monoclonal antibodies
      also specifically blocked IGF-I-induced ERK activation. These effects occurred in
      primary mammary epithelial cells and in two cell lines derived from normal
      mammary epithelium but not in mammary fibroblasts or IGF-I-responsive breast
      carcinoma cell lines. Although IGF-I stimulated the proliferation of both normal
      and carcinoma cell lines, ZD1839 blocked this only in the normal line. ZD1839 had
      no effect on IGF-I receptor (IGF-IR) autophosphorylation in intact cells. IGF-I
      induced ERK activation was insensitive to a broad spectrum matrix
      metalloproteinase inhibitor and to CRM-197, an inhibitor of the EGFR ligand
      heparin-bound epidermal growth factor. EGFR was detectable within IGF-IR
      immunoprecipitates from normal mammary epithelial cells. Treatment of cells with
      IGF-I led to an increase in the amount of tyrosine-phosphorylated EGFR within
      these complexes. ZD1839 had no effect on complex formation but completely
      abolished their associated EGFR tyrosine phosphorylation. These findings indicate
      that IGF-I utilizes a novel EGFR-dependent signaling pathway involving the
      formation of a complex between the IGF-IR and the EGFR to activate the ERK
      pathway and to stimulate proliferation in normal human mammary epithelial cells.
      This form of regulation may be lost during malignant progression.

PMID- 14593114
TI  - Human HRD1 is an E3 ubiquitin ligase involved in degradation of proteins from the
      endoplasmic reticulum.
AB  - The ubiquitin system plays an important role in endoplasmic reticulum (ER)
      associated degradation of proteins that are misfolded, that fail to associate
      with their oligomerization partners, or whose levels are metabolically regulated.
      E3 ubiquitin ligases are key enzymes in the ubiquitination process as they
      recognize the substrate and facilitate coupling of multiple ubiquitin units to
      the protein that is to be degraded. The Saccharomyces cerevisiae ER-resident E3
      ligase Hrd1p/Der3p functions in the metabolically regulated degradation of 3
      hydroxy-3-methylglutaryl-coenzyme A reductase and additionally facilitates the
      degradation of a number of misfolded proteins from the ER. In this study we
      characterized the structure and function of the putative human orthologue of
      yeast Hrd1p/Der3p, designated human HRD1. We show that human HRD1 is a non
      glycosylated, stable ER protein with a cytosolic RING-H2 finger domain. In the
      presence of the ubiquitin-conjugating enzyme UBC7, the RING-H2 finger has in
      vitro ubiquitination activity for Lys(48)-specific polyubiquitin linkage,
      suggesting that human HRD1 is an E3 ubiquitin ligase involved in protein
      degradation. Human HRD1 appears to be involved in the basal degradation of 3
      hydroxy-3-methylglutaryl-coenzyme A reductase but not in the degradation that is
      regulated by sterols. Additionally we show that human HRD1 is involved in the
      elimination of two model ER-associated degradation substrates, TCR-alpha and CD3
      delta.

PMID- 14593115
TI  - Fibroblast growth factor-2 represses platelet-derived growth factor receptor
      alpha (PDGFR-alpha) transcription via ERK1/2-dependent Sp1 phosphorylation and an
      atypical cis-acting element in the proximal PDGFR-alpha promoter.
AB  - Platelet-derived growth factor (PDGF) is a potent mitogen and chemoattractant for
      vascular smooth muscle cells (SMCs) whose biological activity is mediated via its
      high affinity interaction with specific cell surface receptors. The molecular
      mechanisms governing the expression of PDGF receptor-alpha (PDGFR-alpha) are
      poorly understood. Here we demonstrate that PDGFR-alpha protein and
      transcriptional regulation in SMCs is under the positive regulatory influence of
      the zinc finger nuclear protein, Sp1. Electrophoretic mobility shift,
      competition, and supershift analysis revealed the existence of an atypical G-rich
      Sp1-binding element located in the PDGFR-alpha promoter -61 to -52 bp upstream of
      the transcriptional start site. Mutation of this sequence ablated endogenous Sp1
      binding and activation of the PDGFR-alpha promoter. PDGFR-alpha transcription,
      mRNA, and protein expression were repressed in SMCs exposed to fibroblast growth
      factor-2 (FGF-2). This inhibition was rescued by the blockade of extracellular
      signal-regulated kinase-1/2 (ERK1/2). FGF-2 repression of PDGFR-alpha
      transcription was abrogated upon mutation of this Sp1-response element. FGF-2
      stimulated Sp1 phosphorylation in an ERK1/2- but not p38-dependent manner, the
      growth factor enhancing Sp1 interaction with the PDGFR-alpha promoter. Mutation
      of residues Thr(453) and Thr(739) in Sp1 (amino acids phosphorylated by ERK)
      blocked FGF-2 repression of PDGFR-alpha transcription. These findings, taken
      together, demonstrate that FGF-2 stimulates ERK1/2-dependent Sp1 phosphorylation,
      thereby repressing PDGFR-alpha transcription via the -61/-52 element in the PDGFR
      alpha promoter. Phosphorylation triggered by FGF-2 switches Sp1 from an activator
      to a repressor of PDGFR-alpha transcription, a finding previously unreported in
      any Sp1-dependent gene.

PMID- 14593116
TI  - Necdin-related MAGE proteins differentially interact with the E2F1 transcription
      factor and the p75 neurotrophin receptor.
AB  - Necdin is a growth suppressor expressed predominantly in postmitotic neurons and
      implicated in their terminal differentiation. Necdin shows a moderate homology to
      the MAGE family proteins, the functional roles of which are largely unknown.
      Human genes encoding necdin, MAGEL2 (necdin-like 1), and MAGE-G1 (necdin-like 2)
      are located in proximal chromosome 15q, a region associated with
      neurodevelopmental disorders such as Prader-Willi syndrome, Angelman syndrome,
      and autistic disorder. The necdin and MAGEL2 genes are subjected to genomic
      imprinting and suggested to be involved in the etiology of Prader-Willi syndrome.
      In this study, we compared biochemical and functional characteristics of murine
      orthologs of these necdin-related MAGE proteins. The colony formation and
      bromodeoxyuridine incorporation analyses revealed that necdin and MAGE-G1, but
      not MAGEL2, induced growth arrest. Necdin and MAGE-G1 interacted with the
      transcription factor E2F1 via its transactivation domain, repressed E2F1
      dependent transcription, and antagonized E2F1-induced apoptosis of N1E-115
      neuroblastoma cells. In addition, necdin and MAGE-G1 interacted with the p75
      neurotrophin receptor via its distinct intracellular domains. In contrast, MAGEL2
      failed to bind to these necdin interactors, suggesting that MAGEL2 has no necdin
      like function in developing brain. Overexpression of p75 translocated necdin and
      MAGE-G1 in the proximity of the plasma membrane and reduced their association
      with E2F1 to facilitate E2F1-induced death of neuroblastoma cells. These results
      suggest that necdin and MAGE-G1 target both E2F1 and p75 to regulate cell
      viability during brain development.

PMID- 14593117
TI  - High intensity ras signaling induces premature senescence by activating p38
      pathway in primary human fibroblasts.
AB  - Although oncogenic ras plays a pivotal role in neoplastic transformation, it
      triggers an anti-oncogenic defense mechanism known as premature senescence in
      normal cells. In this study, we investigated the induction of cellular responses
      by different expression levels of oncogenic ras in primary human fibroblasts. We
      found that a moderate, severalfold increase in ras expression promoted cell
      growth. Further elevation of ras expression initially enhanced proliferation but
      eventually induced p16INK4A expression and senescence. The induction of these
      opposing cellular responses by ras signals of different intensity was achieved
      through differential activation of the MAPK pathways that mediated these
      responses. Whereas moderate ras activities only stimulated the mitogenic MEK-ERK
      pathway, high intensity ras signals induced MEK and ERK to higher levels, leading
      to stimulation of the MKK3/6-p38 pathway, which had been shown previously to act
      downstream of Ras-MEK to trigger the senescence response. Thus, these studies
      have revealed a mechanism for the differential effects of ras on cell
      proliferation. Furthermore, moderate ras activity mediated transformation in
      cooperation with E6E7 and hTERT, suggesting that a moderate intensity ras signal
      can provide sufficient oncogenic activities for tumorigenesis. This result also
      implies that the ability of ras to promote proliferation and oncogenic
      transformation can be uncoupled with that to induce senescence in cell culture
      and that the development of tumors with relatively low ras activities may not
      need to acquire genetic alterations that bypass premature senescence.

PMID- 14593118
TI  - Cloning and characterization of a GABAA receptor gamma2 subunit variant.
AB  - We have cloned a novel gamma-aminobutyric acid type A (GABAA) receptor gamma2
      subunit variant named gamma2XL. gamma2XL contains an alternatively spliced exon,
      resulting in the addition of 40 amino acids to the N-terminal extracellular
      domain between Ser171 and Tyr172. We show that gamma2XL failed to localize to the
      cell surface when it was coexpressed with the alpha2 and beta1 subunits in human
      embryonic kidney 293 cells. Expression of gamma2XL in 293 cells suppressed GABAA
      receptor binding in a dose-dependent manner by preventing GABAA receptor cell
      surface localization. We also generated a gamma2 mutant with Ser171 and Tyr172
      converted to glycine and threonine, respectively. We demonstrate that this mutant
      has a significantly lower affinity for the alpha2 and beta1 subunits and failed
      to reach the cell surface when coexpressed with these subunits. Together, our
      results indicate that Ser171 and Tyr172 in the gamma2 subunit constitute a
      critical motif. When this motif is disrupted by insertion of the alternative
      exon, access of the gamma2 subunit to the cell surface is prevented.

PMID- 14593119
TI  - Epidermal growth factor receptor activation differentially regulates claudin
      expression and enhances transepithelial resistance in Madin-Darby canine kidney
      cells.
AB  - Tight junctions (TJs) are the most apical cell-cell junctions, and claudins, the
      recently identified TJ proteins, are critical for maintaining cell-cell adhesion
      in epithelial cell sheets. Based on their in vivo distribution and the results of
      overexpression studies, certain claudins, including claudin-1 and -4, are
      postulated to increase, whereas other claudins, especially claudin-2, are
      postulated to decrease the overall transcellular resistance. The overall ratio
      among claudins expressed in a cell/tissue has been hypothesized to define the
      complexity of TJs. Disruption of the TJs contributes to various human diseases,
      and a correlation between reduction of TJ function and tumor dedifferentiation
      has been postulated. The epidermal growth factor (EGF) receptor (EGFR) is
      overexpressed in a wide spectrum of epithelial cancers, and its expression
      correlates with a more metastatic cancer phenotype. However, normal functioning
      of EGFR is essential for normal epithelial cell proliferation and
      differentiation. The role of EGFR-dependent signaling in the development and
      maintenance of epithelial TJ integrity has not been studied in detail. This study
      demonstrates that, in polarized Madin-Darby canine kidney II cells, EGF-induced
      EGFR activation significantly inhibited claudin-2 expression while simultaneously
      inducing cellular redistribution and increased expression of claudin-1, -3, and 
      4. Accompanying these EGF-induced changes in claudin expression was a 3-fold
      increase in transepithelial resistance, a functional measure of TJs. In contrast,
      there were no alterations in protein expression and/or intracellular localization
      of other TJ-related proteins (ZO-1 and occludin) or adherens junction-associated
      proteins (E-cadherin and beta-catenin), suggesting that EGF regulates TJ function
      through selective and differential regulation of claudins.

PMID- 14593120
TI  - Clp protease complexes from photosynthetic and non-photosynthetic plastids and
      mitochondria of plants, their predicted three-dimensional structures, and
      functional implications.
AB  - Tetradecameric Clp protease core complexes in non-photosynthetic plastids of
      roots, flower petals, and in chloroplasts of leaves of Arabidopsis thaliana were
      purified based on native mass and isoelectric point and identified by mass
      spectrometry. The stoichiometry between the subunits was determined. The protease
      complex consisted of one to three copies of five different serine-type protease
      Clp proteins (ClpP1,3-6) and four non-proteolytic ClpR proteins (ClpR1-4). Three
      dimensional homology modeling showed that the ClpP/R proteins fit well together
      in a tetradecameric complex and also indicated unique contributions for each
      protein. Lateral exit gates for proteolysis products are proposed. In addition,
      ClpS1,2, unique to land plants, tightly interacted with this core complex, with
      one copy of each per complex. The three-dimensional modeling show that they do
      fit well on the axial sites of the ClpPR cores. In contrast to plastids, plant
      mitochondria contained a single approximately 320-kDa homo-tetradecameric ClpP2
      complex, without association of ClpR or ClpS proteins. It is surprising that the
      Clp core composition appears identical in all three plastid types, despite the
      remarkable differences in plastid proteome composition. This suggests that
      regulation of plastid proteolysis by the Clp machinery is not through
      differential regulation of ClpP/R/S gene expression, but rather through substrate
      recognition mechanisms and regulated interaction of chaperone-like molecules
      (ClpS1,2 and others) to the ClpP/R core.

PMID- 14593121
TI  - High attenuation and immunogenicity of a simian immunodeficiency virus expressing
      a proteolysis-resistant inhibitor of NF-kappaB.
AB  - NF-kappaB/IkappaB proteins play a major role in the transcriptional regulation of
      human immunodeficiency virus, type-1 (HIV-1). In the case of simian
      immunodeficiency virus (SIV) the cellular factors required for the viral
      transcriptional activation and replication in vivo remain undefined. Here, we
      demonstrate that the p50/p65 NF-kappaB transcription factors enhanced the Tat
      mediated transcriptional activation of SIVmac239. In addition, IkappaB-alpha
      S32/36A, a proteolysis-resistant inhibitor of NF-kappaB, strongly inhibited the
      Tat-mediated transactivation of SIVmac239. Based on this evidence, we have
      generated a self-regulatory virus by endowing the genome of SIV-mac239 with
      IkappaB-alpha S32/36A; the resulting virus, SIVIkappaB-alpha S32/36A, was nef
      deleted and expressed the NF-kappaB inhibitor. We show that SIVIkappaB-alpha
      S32/36A was highly and stably attenuated both in cell cultures and in vivo in
      rhesus macaque as compared with a nef-deleted control virus. Moreover, the high
      attenuation was associated with a robust immune response as measured by SIV
      specific antibody production, tetramer, and intracellular IFN-gamma staining of
      SIV gag-specific T cells. These results underscore the crucial role of NF
      kappaB/IkappaB proteins in the regulation of SIV replication both in cell
      cultures and in monkeys. Thus, inhibitors of NF-kappaB could efficiently
      counteract the SIV/HIV replication in vivo and may assist in developing novel
      approaches for AIDS vaccine and therapy.

PMID- 14593122
TI  - Nitric oxide production and regulation of endothelial nitric-oxide synthase
      phosphorylation by prolonged treatment with troglitazone: evidence for
      involvement of peroxisome proliferator-activated receptor (PPAR) gamma-dependent
      and PPARgamma-independent signaling pathways.
AB  - Recently, peroxisome proliferator-activated receptor gamma (PPARgamma) ligands
      have been reported to increase endothelial NO, but the signaling mechanisms
      involved are unknown. Using troglitazone, a PPARgamma ligand known as an
      antidiabetic compound, we investigated the molecular mechanism of its effect on
      NO production in bovine aortic endothelial cells. Troglitazone increased
      endothelial NO production in a dose- and time-dependent manner with no alteration
      in endothelial nitric-oxide synthase (eNOS) expression. The maximal increase (
      approximately 3.1-fold) was achieved with 20 microm troglitazone treatment for 12
      h, and this increase was accompanied by increases in the expression of vascular
      endothelial growth factor (VEGF) and its receptor, KDR/Flk-1, and in Akt
      phosphorylation. Analysis with antibodies specific for each phosphorylated site
      demonstrated that troglitazone (20 microm treatment for 12 h) significantly
      increased both the phosphorylation of Ser(1179) of eNOS (eNOS-Ser(1179)) and the
      dephosphorylation of eNOS-Ser(116) but did not alter eNOS-Thr(497)
      phosphorylation. Treatment with anti-VEGF antibody to scavenge the increased VEGF
      induced by troglitazone partially inhibited troglitazone-stimulated NO
      production. This was accompanied by the attenuation of troglitazone-stimulated
      increases in the phosphorylation of Akt and eNOS-Ser(1179) with no alteration in
      eNOS-Ser(116) dephosphorylation. We also found that bisphenol A diglycidyl ether,
      a PPARgamma antagonist, partially inhibited troglitazone-stimulated NO production
      with a concomitant reduction in VEGF-KDR/Flk-1-Akt-mediated eNOS-Ser(1179)
      phosphorylation but with no alteration in eNOS-Ser(116) dephosphorylation induced
      by troglitazone. Taken together, our results demonstrate that prolonged treatment
      with troglitazone increases endothelial NO production by at least two independent
      signaling pathways: PPARgamma-dependent, VEGF-KDR/Flk-1-Akt-mediated eNOS
      Ser(1179) phosphorylation and PPARgamma-independent, eNOS-Ser(116)
      dephosphorylation.

PMID- 14593123
TI  - Three-dimensional rearrangements within inositol 1,4,5-trisphosphate receptor by
      calcium.
AB  - Allosteric binding of calcium ion (Ca2+) to inositol 1,4,5-trisphosphate (IP3)
      receptor (IP3R) controls channel gating within IP3R. Here, we present biochemical
      and electron microscopic evidence of Ca2+-sensitive structural changes in the
      three-dimensional structure of type 1 IP3R (IP3R1). Low concentrations of Ca2+
      and high concentrations of Sr2+ and Ba2+ were shown to be effective for the
      limited proteolysis of IP3R1, but Mg2+ had no effect on the proteolysis. The
      electron microscopy and the limited proteolysis consistently demonstrated that
      the effective concentration of Ca2+ for conformational changes in IP3R1 was <10(
      7) m and that the IP3 scarcely affected the conformational states. The structure
      of IP3R1 without Ca2+, as reconstructed by three-dimensional electron microscopy,
      had a "mushroom-like" appearance consisting of a large square-shaped head and a
      small channel domain linked by four thin bridges. The projection image of the
      "head-to-head" assembly comprising two particles confirmed the mushroom-like side
      view. The "windmill-like" form of IP3R1 with Ca2+ also contains the four bridges
      connecting from the IP3-binding domain toward the channel domain. These data
      suggest that the Ca2+-specific conformational change structurally regulates the
      IP3-triggered channel opening within IP3R1.

PMID- 14593124
TI  - Interactions between p-33 and p-55 domains of the Helicobacter pylori vacuolating
      cytotoxin (VacA).
AB  - The VacA toxin secreted by Helicobacter pylori is considered to be an important
      virulence factor in the pathogenesis of peptic ulcer disease and gastric cancer.
      VacA monomers self-assemble into water-soluble oligomeric structures and can form
      anion-selective membrane channels. The goal of this study was to characterize
      VacA-VacA interactions that may mediate assembly of VacA monomers into higher
      order structures. We investigated potential interactions between two domains of
      VacA (termed p-33 and p-55) by using a yeast two-hybrid system. p-33/p-55
      interactions were detected in this system, whereas p-33/p-33 and p-55/p-55
      interactions were not detected. Several p-33 proteins containing internal
      deletion mutations were unable to interact with wild-type p-55 in the yeast two
      hybrid system. Introduction of these same deletion mutations into the H. pylori
      vacA gene resulted in secretion of mutant VacA proteins that failed to assemble
      into large oligomeric structures and that lacked vacuolating toxic activity for
      HeLa cells. Additional mapping studies in the yeast two-hybrid system indicated
      that only the N-terminal portion of the p-55 domain is required for p-33/p-55
      interactions. To characterize further p-33/p-55 interactions, we engineered an H.
      pylori strain that produced a VacA toxin containing an enterokinase cleavage site
      located between the p-33 and p-55 domains. Enterokinase treatment resulted in
      complete proteolysis of VacA into p-33 and p-55 domains, which remained
      physically associated within oligomeric structures and retained vacuolating
      cytotoxin activity. These results provide evidence that interactions between p-33
      and p-55 domains play an important role in VacA assembly into oligomeric
      structures.

PMID- 14593125
TI  - Validation of computed tomographic middle cerebral artery "dot"sign: an
      angiographic correlation study.
AB  - BACKGROUND AND PURPOSE: The middle cerebral artery (MCA) "dot" sign consists of
      hyperdensity of an arterial structure, seen as a dot in the sylvian fissure. The
      MCA dot sign has been proposed to indicate thrombosis of M2 or M3 MCA branches,
      analogous to the hyperdense middle cerebral artery (HMCA) sign indicating M1
      thrombosis. The MCA dot sign has not been validated previously against the gold
      standard of conventional cerebral angiography. METHODS: Noncontrast CT scans and
      immediately subsequent cerebral angiograms from 54 acute stroke patients within 8
      hours of symptom onset were analyzed. CT films were inspected for the MCA dot
      sign and HMCA sign. Vascular findings on CT were compared with findings at
      angiography. RESULTS: Mean patient age was 71 years; median National Institutes
      of Health Stroke Scale score was 16.5. Mean time from symptom onset to CT was 125
      minutes, and that from CT to angiography was 117 minutes. All patients had
      arterial occlusion at angiography. Of the anterior circulation occlusions, M1
      occlusions were noted in 28 patients, isolated M2 in 15, and isolated M3 in 4.
      One definite MCA dot sign was observed in 16.7% of patients, and an HMCA sign was
      observed in 13.9%. MCA dot sign performance in predicting the presence of M2 or
      M3 clot at angiography was as follows: sensitivity 38%, specificity 100%,
      positive predictive value 100%, negative predictive value 68%, and overall
      accuracy 73%. CONCLUSIONS: The MCA dot sign is a highly specific and moderately
      sensitive indicator of acute thrombus in the M2/M3 MCA branches, as validated by
      catheter angiography. The MCA dot sign is a useful additional acute stroke CT
      marker.

PMID- 14593127
TI  - Effect of treatment of carotid artery stenosis on blood pressure: a comparison of
      hemodynamic disturbances after carotid endarterectomy and endovascular treatment.
AB  - BACKGROUND AND PURPOSE: Carotid intervention by carotid endarterectomy (CEA) or
      endovascular treatment may cause hemodynamic change. The immediate and long-term
      effects on blood pressure after these procedures were assessed. METHODS: Patients
      were randomized to CEA (n=49) or endovascular treatment (n=55) that comprised
      percutaneous transluminal angioplasty alone (n=31), balloon-expandable stent
      (n=13), or self-expandable stent (n=11). A baseline 24-hour ambulatory blood
      pressure recording was made before carotid intervention and repeated at 24 hours,
      1 month, and 6 months after the procedure. RESULTS: In the first 24 hours after
      the procedure, episodes of hypotension occurred in 75% of the CEA group and 76%
      of the endovascular group; hypertension occurred in 11% and 13%, respectively.
      There was a significant fall in blood pressure at 1 hour after the procedure in
      both groups (24 and 16 mm Hg fall in CEA and endovascular groups, respectively),
      but this was only sustained in the endovascular group. The pattern of blood
      pressure response in the first 24 hours was significantly different (P<0.0001,
      ANCOVA). Systolic blood pressure was significantly lower at 1 and 6 months only
      in the surgical group (6 and 5 mm Hg fall, respectively). CONCLUSIONS: Both CEA
      and endovascular treatment have an effect on blood pressure stability,
      particularly within the first 24 hours after the procedure.

PMID- 14593126
TI  - Relationship between blood pressure and stroke risk in patients with symptomatic
      carotid occlusive disease.
AB  - BACKGROUND AND PURPOSE: Blood pressure lowering in patients with a previous
      transient ischemic attack (TIA) or stroke reduces the risk of recurrent stroke
      and coronary vascular events. However, there is uncertainty about the risks and
      benefits in patients with severe carotid occlusive disease, particularly those
      with a carotid occlusion or bilateral > or =70% carotid stenosis in whom cerebral
      perfusion is often impaired and may depend directly on systemic blood pressure.
      Therefore, we studied the effect of carotid artery disease on the relationship
      between blood pressure and stroke risk in patients with recent TIA or stroke.
      METHODS: We compared the relationship between blood pressure (systolic and
      diastolic blood pressures, pulse pressure) and stroke risk in TIA and stroke
      patients with documented stenosis of at least 1 carotid artery [European Carotid
      Surgery Trial (ECST) and North American Symptomatic Carotid Endarterectomy Trial
      (NASCET)] with that in TIA and stroke patients with a low prevalence of carotid
      disease [United Kingdom Transient Ischaemic Attack (UK-TIA) Aspirin Trial]. In
      ECST and NASCET, we also determined the relationship between blood pressure and
      stroke risk in patients with unilateral carotid occlusion and patients with
      bilateral > or =70% carotid stenosis. RESULTS: Stroke risk on medical treatment
      increased with blood pressure in ECST and NASCET, but the relationships were less
      steep than in the UK-TIA trial. The relationship between blood pressure and
      stroke risk was not affected by the presence of a unilateral carotid occlusion
      but was significantly affected by the presence of bilateral carotid stenosis > or
      =70% (interaction: systolic blood pressure, P=0.002; diastolic blood pressure,
      P=0.03; pulse pressure, P=0.003). In this group, the relationship was inverted
      because of the high stroke risks at lower blood pressures. This interaction was
      not present after carotid endarterectomy and was not present for the risk of
      myocardial infarction. CONCLUSIONS: The risk of stroke increases with blood
      pressure in the great majority of patients with symptomatic carotid artery
      disease, but the relationship is less steep than in other patients with TIA or
      stroke. The relationship is unaffected by unilateral carotid occlusion alone but
      is inverted in patients with bilateral > or =70% carotid stenosis, suggesting
      that aggressive blood pressure lowering may not be advisable in this group. These
      patients represent only a few percent of all patients with TIA or stroke but have
      a high risk of recurrent stroke.

PMID- 14593128
TI  - Stroke is best managed by a neurologist: battle of the titans.

PMID- 14593129
TI  - Neurologist, internist, or strokologist?

PMID- 14593130
TI  - Editorial comment--Blood pressure lowering for the secondary prevention of
      stroke: one size fits all?

PMID- 14593131
TI  - Stroke is best managed by neurologists.

PMID- 14593132
TI  - Editorial comment--Hypotension after carotid revascularization.

PMID- 14593133
TI  - Editorial comment--Down with the class society!

PMID- 14593134
TI  - Genetic discrimination: time to act.

PMID- 14593135
TI  - Biomedical politics. NIH roiled by inquiries over grants hit list.

PMID- 14593136
TI  - Glaciology. Warmer ocean could threaten Antarctic ice shelves.

PMID- 14593137
TI  - Forensic geochemistry. Isotopic data pinpoint Iceman's origins.

PMID- 14593138
TI  - Cosmology. Galaxy maps support theory that the universe is flying to pieces.

PMID- 14593139
TI  - Energy research. DOE told to make its science more visible.

PMID- 14593140
TI  - Medicine. In a first, infected mice recover from prion disease.

PMID- 14593141
TI  - Endangered species. NRC backs ecosystem-wide changes to save Klamath fish.

PMID- 14593142
TI  - Infectious diseases. Search for SARS origins stalls.

PMID- 14593143
TI  - Infectious diseases. Unexplained false alarm may hold lessons.

PMID- 14593144
TI  - Ecology. Methuselahs in our midst.

PMID- 14593146
TI  - Marine research. Scientists counting on census to reveal marine biodiversity.

PMID- 14593145
TI  - Paleontology. Peering into ancient ears.

PMID- 14593147
TI  - Symbiosis. Fast friends, sworn enemies.

PMID- 14593148
TI  - Tracking children's health to age 21.

PMID- 14593149
TI  - Agricultural IP and the public sector.

PMID- 14593150
TI  - Forgery: prediction's vile twin.

PMID- 14593151
TI  - Comment on "Salt-pump mechanism for contaminant intrusion into coastal aquifers".

PMID- 14593153
TI  - Information science. Going, going, gone: lost Internet references.
AB  - The use of Internet references in academic literature is common, and Internet
      references are frequently inaccessible. The extent of Internet referencing and
      Internet reference activity in medical or scientific publications was
      systematically examined in more than 1000 articles published between 2000 and
      2003 in the New England Journal of Medicine, The Journal of the American Medical
      Association, and Science. Internet references accounted for 2.6% of all
      references (672/25548) and in articles 27 months old, 13% of Internet references
      were inactive. Publishers, librarians, and readers need to reassess policies,
      archiving systems, and other resources for addressing Internet reference
      attrition to prevent further information loss.

PMID- 14593154
TI  - Neuroscience. Illusions and perceived images in the primate brain.

PMID- 14593155
TI  - Ocean science. Who threw that snowball?

PMID- 14593156
TI  - Chemistry. Ionic liquids--solvents of the future?

PMID- 14593158
TI  - Physics. Searching for gravity's hidden strength.

PMID- 14593157
TI  - Molecular biology. MeCP2 repression goes nonglobal.

PMID- 14593159
TI  - Ecology. Vole stranglers and lemming cycles.

PMID- 14593161
TI  - 2003 Grand Prize winner.

PMID- 14593160
TI  - Eppendorf 2003 prize-winning essay. Ubiquitin and the deconstruction of synapses.

PMID- 14593163
TI  - In sickness or in health?

PMID- 14593164
TI  - Future brightening for depression treatments.

PMID- 14593165
TI  - Games played by rogue proteins in prion disorders and Alzheimer's disease.
AB  - The incidence of Alzheimer's disease (AD) and that of prion disorders (PrD) could
      not be more different. One-third of octogenarians succumb to AD, whereas
      Creutzfeldt-Jakob disease typically affects one individual in a million each
      year. However, these diseases have many common features impinging on the
      metabolism of neuronal membrane proteins: the amyloid precursor protein APP in
      the case of AD, and the cellular prion protein PrPC in PrD. APP begets the Abeta
      peptide, whereas PrPC begets the malignant prion protein PrPSc. Both Abeta and
      PrPSc are associated with disease, but we do not know what triggers their
      accumulation and neurotoxicity. A great deal has been learned, however, about
      protein folding, misfolding, and aggregation; an entirely new class of
      intramembrane proteases has been identified; and unsuspected roles for the immune
      system have been uncovered. There is reason to expect that prion research will
      profit from advances in the understanding of AD, and vice versa.

PMID- 14593166
TI  - Molecular pathways of neurodegeneration in Parkinson's disease.
AB  - Parkinson's disease (PD) is a complex disorder with many different causes, yet
      they may intersect in common pathways, raising the possibility that
      neuroprotective agents may have broad applicability in the treatment of PD.
      Current evidence suggests that mitochondrial complex I inhibition may be the
      central cause of sporadic PD and that derangements in complex I cause alpha
      synuclein aggregation, which contributes to the demise of dopamine neurons.
      Accumulation and aggregation of alpha-synuclein may further contribute to the
      death of dopamine neurons through impairments in protein handling and
      detoxification. Dysfunction of parkin (a ubiquitin E3 ligase) and DJ-1 could
      contribute to these deficits. Strategies aimed at restoring complex I activity,
      reducing oxidative stress and alpha-synuclein aggregation, and enhancing protein
      degradation may hold particular promise as powerful neuroprotective agents in the
      treatment of PD.

PMID- 14593167
TI  - The genetics of adult-onset neuropsychiatric disease: complexities and conundra?
AB  - Genetic factors play a major role in the etiology of adult-onset
      neurodegenerative and neuropsychiatric disorders. Several highly penetrant genes
      have been cloned for rare, autosomal-dominant, early-onset forms of
      neurodegenerative diseases. These genes have provided important insights into the
      mechanisms of these diseases (often altering neuronal protein processing).
      However, the genes associated with inherited susceptibility to late-onset
      neurodegenerative diseases, schizophrenia, and bipolar disorder appear to have
      smaller effects and are likely to interact with each other (and with nongenetic
      factors) to modulate susceptibility and/or disease phenotype. Several strategies
      have recently been applied to address this complexity, leading to the
      identification of a number of candidate susceptibility loci/genes.

PMID- 14593168
TI  - Postnatal neurodevelopmental disorders: meeting at the synapse?
AB  - We often think of neurodevelopmental disorders as beginning before birth, and
      many certainly do. A handful, however, strike many months after birth, following
      a period of apparently normal growth and development. Autism and Rett syndrome
      are two such disorders, and here I consider some of their similarities at the
      phenotypic and pathogenic levels. I propose that both disorders result from
      disruption of postnatal or experience-dependent synaptic plasticity.

PMID- 14593169
TI  - Looking backward to move forward: early detection of neurodegenerative disorders.
AB  - Early detection of neurodegenerative disorders would provide clues to the
      underlying pathobiology of these diseases and would enable more effective
      diagnosis and treatment of patients. Recent advances in molecular neuroscience
      have begun to provide the tools to detect diseases like Alzheimer's disease,
      Parkinson's disease, and others early in their course and potentially even before
      the development of clinical manifestations of disease. These genetic, imaging,
      clinical, and biochemical tools are being validated in a number of studies. Early
      detection of these slowly progressive diseases offers the promise of
      presymptomatic diagnosis and, ultimately, of disease-modifying medications for
      use early in disease and during the presymptomatic period.

PMID- 14593170
TI  - Immunotherapeutic approaches to Alzheimer's disease.
AB  - Although neurodegenerative diseases such as Alzheimer's disease are not
      classically considered mediated by inflammation or the immune system, in some
      instances the immune system may play an important role in the degenerative
      process. Furthermore, it has become clear that the immune system itself may have
      beneficial effects in nervous system diseases considered neurodegenerative.
      Immunotherapeutic approaches designed to induce a humoral immune response have
      recently been developed for the treatment of Alzheimer's disease. These studies
      have led to human trials that resulted in both beneficial and adverse effects. In
      animal models, it has also been shown that immunotherapy designed to induce a
      cellular immune response may be of benefit in central nervous system injury,
      although T cells may have either a beneficial or detrimental effect depending on
      the type of T cell response induced. These areas provide a new avenue for
      exploring immune system-based therapy of neurodegenerative diseases and will be
      discussed here with a primary focus on Alzheimer's disease. We will also discuss
      how these approaches affect microglia activation, which plays a key role in
      therapy of such diseases.

PMID- 14593171
TI  - alpha-Synuclein locus triplication causes Parkinson's disease.

PMID- 14593173
TI  - Direct atom-resolved imaging of oxides and their grain boundaries.
AB  - Using high-resolution transmission electron microscopy, we obtained structure
      images of strontium titanate (SrTiO3) with a clearly resolved oxygen sublattice
      along different crystallographic directions in the bulklattice and for a Sigma3
      tilt grain boundary. Comparison with image simulations showed that the grain
      boundary contains oxygen vacancies. Measurements of atom displacements near the
      grain boundary revealed close correspondence with theoretical calculations.

PMID- 14593172
TI  - Empirical analysis of transcriptional activity in the Arabidopsis genome.
AB  - Functional analysis of a genome requires accurate gene structure information and
      a complete gene inventory. A dual experimental strategy was used to verify and
      correct the initial genome sequence annotation of the reference plant
      Arabidopsis. Sequencing full-length cDNAs and hybridizations using RNA
      populations from various tissues to a set of high-density oligonucleotide arrays
      spanning the entire genome allowed the accurate annotation of thousands of gene
      structures. We identified 5817 novel transcription units, including a substantial
      amount of antisense gene transcription, and 40 genes within the genetically
      defined centromeres. This approach resulted in completion of approximately 30% of
      the Arabidopsis ORFeome as a resource for global functional experimentation of
      the plant proteome.

PMID- 14593174
TI  - Is the fragility of a liquid embedded in the properties of its glass?
AB  - When a liquid is cooled below its melting temperature, it usually crystallizes.
      However, if the quenching rate is fast enough, the system may remain in a
      disordered state, progressively losing its fluidity upon further cooling. When
      the time needed for the rearrangement of the local atomic structure reaches
      approximately 100 seconds, the system becomes "solid" for any practical purpose,
      and this defines the glass transition temperature Tg. Approaching this transition
      from the liquid side, different systems show qualitatively different temperature
      dependencies of the viscosity, and accordingly they have been classified by
      introducing the concept of "fragility." We report experimental observations that
      relate the microscopic properties of the glassy phase to the fragility. We find
      that the vibrational properties of the glass well below Tg are correlated with
      the fragility value. Consequently, we extend the fragility concept to the glassy
      state and indicate how to determine the fragility uniquely from glass properties
      well below Tg.

PMID- 14593175
TI  - Decadal variation of the surface water PCO2 in the western and central equatorial
      Pacific.
AB  - The equatorial Pacific Ocean is one of the most important yet highly variable
      oceanic source areas for atmospheric carbon dioxide (CO2). Here, we used the
      partial pressure of CO2 (PCO2), measured in surface waters from 1979 through
      early 2001, to examine the effect on the equatorial Pacific CO2 chemistry of the
      Pacific Decadal Oscillation phase shift, which occurred around 1988 to 1992.
      During the decade before the shift, the surface water PCO2 (corrected for
      temperature changes and atmospheric CO2 uptake) in the central and western
      equatorial Pacific decreased at a mean rate of about -20 microatm per decade,
      whereas after the shift, it increased at about +15 microatm per decade. These
      changes altered the CO2 sink and source flux of the equatorial Pacific
      significantly.

PMID- 14593176
TI  - Larsen ice shelf has progressively thinned.
AB  - The retreat and collapse of Antarctic Peninsula ice shelves in tandem with a
      regional atmospheric warming has fueled speculation as to how these events may be
      related. Satellite radar altimeter measurements show that between 1992 and 2001
      the Larsen Ice Shelf lowered by up to 0.27 +/- 0.11 meters per year. The lowering
      is explained by increased summer melt-water and the loss of basal ice through
      melting. Enhanced ocean-driven melting may provide a simple link between regional
      climate warming and the successive disintegration of sections of the Larsen Ice
      Shelf.

PMID- 14593177
TI  - Carbonate deposition, climate stability, and Neoproterozoic ice ages.
AB  - The evolutionary success of planktic calcifiers during the Phanerozoic stabilized
      the climate system by introducing a new mechanism that acts to buffer ocean
      carbonate-ion concentration: the saturation-dependent preservation of carbonate
      in sea-floor sediments. Before this, buffering was primarily accomplished by
      adjustment of shallow-water carbonate deposition to balance oceanic inputs from
      weathering on land. Neoproterozoic ice ages of near-global extent and
      multimillion-year duration and the formation of distinctive sedimentary (cap)
      carbonates can thus be understood in terms of the greater sensitivity of the
      Precambrian carbon cycle to the loss of shallow-water environments and CO2
      climate feedback on ice-sheet growth.

PMID- 14593178
TI  - Origin and migration of the Alpine Iceman.
AB  - The Alpine Iceman provides a unique window into the Neolithic-Copper Age of
      Europe. We compared the radiogenic (strontium and lead) and stable (oxygen and
      carbon) isotope composition of the Iceman's teeth and bones, as well as 40Ar/39Ar
      mica ages from his intestine, to local geology and hydrology, and we inferred his
      habitat and range from childhood to adult life. The Iceman's origin can be
      restricted to a few valleys within approximately 60 kilometers south(east) of the
      discovery site. His migration during adulthood is indicated by contrasting
      isotopic compositions of enamel, bones, and intestinal content. This demonstrates
      that the Alpine valleys of central Europe were permanently inhabited during the
      terminal Neolithic.

PMID- 14593179
TI  - Cyclic dynamics in a simple vertebrate predator-prey community.
AB  - The collared lemming in the high-Arctic tundra in Greenland is preyed upon by
      four species of predators that show marked differences in the numbers of lemmings
      each consumes and in the dependence of their dynamics on lemming density. A
      predator prey model based on the field-estimated predator responses robustly
      predicts 4-year periodicity in lemming dynamics, in agreement with long-term
      empirical data. There is no indication in the field that food or space limits
      lemming population growth, nor is there need in the model to consider those
      factors. The cyclic dynamics are driven by a 1-year delay in the numerical
      response of the stoat and stabilized by strongly density-dependent predation by
      the arctic fox, the snowy owl, and the long-tailed skua.

PMID- 14593180
TI  - A four-base paired genetic helix with expanded size.
AB  - We describe a new molecular class of genetic-pairing system that has a native DNA
      backbone but has all four base pairs replaced by new, larger pairs. The base
      pairs include size-expanded analogs of thymine and of adenine, both extended by
      the width of a benzene ring (2.4 A). The expanded-diameter double helices are
      more thermodynamically stable than the Watson-Crick helix, likely because of
      enhanced base stacking. Structural data confirm a right-handed, double-stranded,
      and base-paired helical form. Because of the larger base size, all the pairs of
      this helical system are fluorescent, which suggests practical applications in
      detection of natural DNA and RNA. Our findings establish that there is no
      apparent structural or thermodynamic prohibition against genetic systems having
      sizes different from the natural one.

PMID- 14593181
TI  - Depleting neuronal PrP in prion infection prevents disease and reverses
      spongiosis.
AB  - The mechanisms involved in prion neurotoxicity are unclear, and therapies
      preventing accumulation of PrPSc, the disease-associated form of prion protein
      (PrP), do not significantly prolong survival in mice with central nervous system
      prion infection. We found that depleting endogenous neuronal PrPc in mice with
      established neuroinvasive prion infection reversed early spongiform change and
      prevented neuronal loss and progression to clinical disease. This occurred
      despite the accumulation of extraneuronal PrPSc to levels seen in terminally ill
      wild-type animals. Thus, the propagation of nonneuronal PrPSc is not pathogenic,
      but arresting the continued conversion of PrPc to PrPSc within neurons during
      scrapie infection prevents prion neurotoxicity.

PMID- 14593182
TI  - Prevention of organ allograft rejection by a specific Janus kinase 3 inhibitor.
AB  - Because of its requirement for signaling by multiple cytokines, Janus kinase 3
      (JAK3) is an excellent target for clinical immunosuppression. We report the
      development of a specific, orally active inhibitor of JAK3, CP-690,550, that
      significantly prolonged survival in a murine model of heart transplantation and
      in cynomolgus monkeys receiving kidney transplants. CP-690,550 treatment was not
      associated with hypertension, hyperlipidemia, or lymphoproliferative disease. On
      the basis of these preclinical results, we believe JAK3 blockade by CP-690,550
      has potential for therapeutically desirable immunosuppression in human organ
      transplantation and in other clinical settings.

PMID- 14593183
TI  - Derepression of BDNF transcription involves calcium-dependent phosphorylation of
      MeCP2.
AB  - Mutations in MeCP2, which encodes a protein that has been proposed to function as
      a global transcriptional repressor, are the cause of Rett syndrome (RT T), an X
      linked progressive neurological disorder. Although the selective inactivation of
      MeCP2 in neurons is sufficient to confer a Rett-like phenotype in mice, the
      specific functions of MeCP2 in postmitotic neurons are not known. We find that
      MeCP2 binds selectively to BDNF promoter III and functions to repress expression
      of the BDNF gene. Membrane depolarization triggers the calcium-dependent
      phosphorylation and release of MeCP2 from BDNF promoter III, thereby facilitating
      transcription. These studies indicate that MeCP2 plays a key role in the control
      of neuronal activity-dependent gene regulation and suggest that the deregulation
      of this process may underlie the pathology of RT T.

PMID- 14593184
TI  - DNA methylation-related chromatin remodeling in activity-dependent BDNF gene
      regulation.
AB  - In conjunction with histone modifications, DNA methylation plays critical roles
      in gene silencing through chromatin remodeling. Changes in DNA methylation
      perturb neuronal function, and mutations in a methyl-CpG-binding protein, MeCP2,
      are associated with Rett syndrome. We report that increased synthesis of brain
      derived neurotrophic factor (BDNF) in neurons after depolarization correlates
      with a decrease in CpG methylation within the regulatory region of the Bdnf gene.
      Moreover, increased Bdnf transcription involves dissociation of the MeCP2-histone
      deacetylase-mSin3A repression complex from its promoter. Our findings suggest
      that DNA methylation-related chromatin remodeling is important for activity
      dependent gene regulation that may be critical for neural plasticity.

PMID- 14593185
TI  - Negative feedback regulation ensures the one receptor-one olfactory neuron rule
      in mouse.
AB  - In the mouse olfactory system, each olfactory sensory neuron (OSN) expresses only
      one odorant receptor (OR) gene in a monoallelic and mutually exclusive manner.
      Such expression forms the genetic basis for OR-instructed axonal projection of
      OSNs to the olfactory bulb of the brain during development. Here, we identify an
      upstream cis-acting DNA region that activates the OR gene cluster in mouse and
      allows the expression of only one OR gene within the cluster. Deletion of the
      coding region of the expressed OR gene or a naturally occurring frame-shift
      mutation allows a second OR gene to be expressed. We propose that stochastic
      activation of only one OR gene within the cluster and negative feedback
      regulation by that OR gene product are necessary to ensure the one receptor-one
      neuron rule.

PMID- 14593186
TI  - Quantum cascade surface-emitting photonic crystal laser.
AB  - We combine photonic and electronic band structure engineering to create a surface
      emitting quantum cascade microcavity laser. A high-index contrast two-dimensional
      photonic crystal is used to form a micro-resonator that simultaneously provides
      feedback for laser action and diffracts light vertically from the surface of the
      semiconductor surface. A top metallic contact allows electrical current injection
      and provides vertical optical confinement through a bound surface plasmon wave.
      The miniaturization and tailorable emission properties of this design are
      potentially important for sensing applications, while electrical pumping can
      allow new studies of photonic crystal and surface plasmon structures in nonlinear
      and near-field optics.

PMID- 14593187
TI  - Regulation of flowering time by histone acetylation in Arabidopsis.
AB  - The Arabidopsis autonomous floral-promotion pathway promotes flowering
      independently of the photoperiod and vernalization pathways by repressing
      FLOWERING LOCUS C (FLC), a MADS-box transcription factor that blocks the
      transition from vegetative to reproductive development. Here, we report that
      FLOWERING LOCUS D (FLD), one of six genes in the autonomous pathway, encodes a
      plant homolog of a protein found in histone deacetylase complexes in mammals.
      Lesions in FLD result in hyperacetylation of histones in FLC chromatin, up
      regulation of FLC expression, and extremely delayed flowering. Thus, the
      autonomous pathway regulates flowering in part by histone deacetylation. However,
      not all autonomous-pathway mutants exhibit FLC hyperacetylation, indicating that
      multiple means exist by which this pathway represses FLC expression.

PMID- 14593188
TI  - Special Topics III: bias.
AB  - Researchers, manuscript reviewers, and journal readers should be aware of the
      many potential sources of bias in radiologic studies. This article is a review of
      the common biases that occur in selecting patient and reader samples, choosing
      and applying a reference standard, performing and interpreting diagnostic
      examinations, and analyzing diagnostic test results. Potential implications of
      various biases are discussed, and practical approaches to eliminating or
      minimizing them are presented.

PMID- 14593189
TI  - Breast MR imaging during or soon after radiation therapy.
AB  - PURPOSE: To investigate the degree and prevalence of radiation-induced changes on
      breast magnetic resonance (MR) images in patients who were undergoing radiation
      therapy at that time or soon after, to assess prospectively whether possible
      radiation-induced effects impair diagnostic accuracy of imaging, and to
      investigate the prevalence of residual ipsilateral and synchronous contralateral
      breast cancer in patients undergoing radiation therapy after resection of a
      supposedly solitary breast cancer. MATERIALS AND METHODS: A total of 116 dynamic
      bilateral breast MR studies were performed during and up to 12 months after
      radiation therapy in 72 patients who had undergone breast-conservation surgery
      without preoperative MR imaging. Patients were assigned to four groups according
      to the time span between imaging and radiation therapy. Structural changes,
      parenchymal enhancement pattern, and prevalence and imaging features of
      incidental lesions were analyzed and compared with those of the nonirradiated
      breast. RESULTS: Radiation therapy led to parenchymal edema and a significant
      (two-tailed paired Student t test) increase in enhancement rates in the
      irradiated compared with those in the contralateral breasts during and up to 3
      months after radiation therapy. Neither during nor at any time after radiation
      therapy did the mean enhancement rates reach diagnostically relevant rates.
      Unsuspected residual or recurrent breast cancers were identified in irradiated
      breasts of five patients and in contralateral breasts of two patients. False
      positive MR findings resulted in a biopsy in three patients with irradiated and
      in one patient with nonirradiated breasts. There was no difference in enhancement
      kinetics or morphology of benign or malignant lesions in irradiated versus
      nonirradiated breasts. CONCLUSION: Radiation-induced changes occur at MR imaging
      during or up to 3 months after radiation therapy but are much less severe than
      reported. Detection and characterization of lesions were feasible with comparable
      diagnostic accuracies in irradiated and nonirradiated breasts.

PMID- 14593191
TI  - Bone marrow with diffuse tumor infiltration in patients with lymphoproliferative
      diseases: dynamic gadolinium-enhanced MR imaging.
AB  - PURPOSE: To evaluate gadolinium enhancement of bone marrow in patients with
      lymphoproliferative diseases and diffuse bone marrow involvement. MATERIALS AND
      METHODS: Dynamic contrast material-enhanced magnetic resonance (MR) imaging of
      the thoracolumbar spine was performed in 42 patients with histologically proved
      diffuse bone marrow involvement and newly diagnosed myeloma (n = 31), non-Hodgkin
      lymphoma (n = 8), or Hodgkin disease (n = 3). The maximum percentage of
      enhancement (Emax), enhancement slope, and enhancement washout were determined
      from enhancement time curves (ETCs). A three-grade system for scoring bone marrow
      involvement was based on the percentage of neoplastic cells in bone marrow
      samples. Quantitative ETC values for the 42 patients were compared with ETC
      values for healthy subjects and with grades of bone marrow involvement by using
      mean t test comparisons. Receiver operating characteristic (ROC) analysis was
      conducted by comparing Emax values between patients with and those without bone
      marrow involvement. Baseline and follow-up MR imaging findings were compared in
      nine patients. RESULTS: Significant differences in Emax (P <.001), slope (P
      <.001), and washout (P =.005) were found between subjects with normal bone marrow
      and patients with diffuse bone marrow involvement. ROC analysis results showed
      Emax values to have a diagnostic accuracy of 99%. Emax, slope, and washout values
      increased with increasing bone marrow involvement grade. The mean Emax increased
      from 339% to 737%. Contrast enhancement decreased after treatment in all six
      patients who responded to treatment but not in two of three patients who did not
      respond to treatment. CONCLUSION: Dynamic contrast-enhanced MR images can
      demonstrate increased bone marrow enhancement in patients with
      lymphoproliferative diseases and marrow involvement.

PMID- 14593190
TI  - Normal spinal bone marrow in adults: dynamic gadolinium-enhanced MR imaging.
AB  - PURPOSE: To determine the patterns of dynamic enhancement of normal spinal bone
      marrow in adults at gadolinium-enhanced magnetic resonance (MR) imaging and the
      changes that occur with aging. MATERIALS AND METHODS: Dynamic contrast material
      enhanced MR imaging of the thoracolumbar spine was performed in 71 patients. The
      maximum percentage of enhancement (Emax), enhancement slope, and enhancement
      washout were determined from bone marrow enhancement time curves (ETCs). The bone
      marrow signal intensity on T1-weighted spin-echo MR images was qualitatively
      classified into three grade categories. Quantitative ETC values were correlated
      with patient age and bone marrow fat content grade. Statistical analysis included
      mean t test comparison, analysis of variance, and regression analysis of the
      correlations between age and quantitative MR parameters. RESULTS: Emax, slope,
      and washout varied widely among the patients. Emax values were obtained within 1
      minute after contrast material injection and ranged from 0% to 430%. Emax values
      were significantly higher in patients younger than 40 years than in those aged 40
      years or older (P <.001). These values decreased with increasing age in a
      logarithmic relationship (r = 0.71). Emax values decreased as fat content
      increased, but some overlap among the fat content grades was noted. Analysis of
      variance revealed that Emax was significantly related to age (younger than 40
      years vs 40 years or older) (P <.001) and fat content grade (P <.001) but not
      significantly related to sex. CONCLUSION: Dynamic contrast-enhanced MR imaging
      patterns of normal spinal bone marrow are dependent mainly on patient age and fat
      content.

PMID- 14593192
TI  - Living donor kidneys: usefulness of multi-detector row CT for comprehensive
      evaluation.
AB  - PURPOSE: To evaluate in living renal donors the usefulness of multi-detector row
      computed tomography (CT) in the assessment of renal vasculature and the upper
      urinary tract. MATERIALS AND METHODS: Four-channel multi-detector row CT scans
      were obtained in 77 patients. Vascular phase scans were used for CT angiography;
      excretory phase scans, for CT urography. At CT angiography, two independent
      observers evaluated the number of arteries and veins and the presence of early
      branching arteries. CT urographic images were evaluated with regard to the
      opacification of the urinary tract and for abnormalities. Findings of CT
      angiography and urography were compared with surgical findings. Interobserver
      agreement between CT angiographic and surgical findings was quantified with
      weighted kappa statistics. Sensitivity and specificity of CT angiography in
      identifying supernumerary vessels and early-branching arteries were also
      evaluated. To evaluate the radiation dose to patients, weighted CT dose index
      (DI) was assessed for each scan. RESULTS: Agreement between CT angiographic and
      surgical findings was excellent for the number of renal arteries (kappa = 0.896)
      and veins (kappa = 0.843). Detection rate of CT angiography was 98% (89 of 91)
      for arteries and 98% (83 of 85) for veins. The respective sensitivity and
      specificity of CT angiography were 86% (12 of 14) and 100% (65 of 65) for
      supernumerary arteries, 100% (11 of 11) and 100% (66 of 66) for early-branching
      arteries, and 75% (six of eight) and 100% (69 of 69) for supernumerary veins. At
      CT urography, collecting systems and proximal ureters were well opacified in all
      patients; two patients had underrotated kidneys without obstruction. The weighted
      CT DI was 10.19 mGy for unenhanced and excretory phase scans and 12.88 mGy for
      the vascular phase scan. CONCLUSION: Multi-detector row CT can help assess well
      the renal vasculature and the urinary tract of living renal donors.

PMID- 14593193
TI  - Fluorodeoxyglucose uptake in the aortic wall at PET/CT: possible finding for
      active atherosclerosis.
AB  - PURPOSE: To evaluate fluorine 18 fluorodeoxyglucose (FDG) uptake in the thoracic
      aortic wall at combined positron emission tomography (PET)/computed tomography
      (CT) and compare uptake with aortic wall calcification. MATERIALS AND METHODS:
      Records of 85 consecutive cancer patients who underwent FDG PET/CT were evaluated
      retrospectively. One hour after FDG injection, CT followed by PET was performed
      from ear to middle of the thigh. CT, PET, and fused PET/CT images were generated.
      FDG uptake and calcification were evaluated visually and semiquantitatively. FDG
      uptake was graded according to intensity; calcification, according to thickness.
      Unpaired t test was used for comparison of patient age with and without FDG
      uptake and with and without calcification. The relationship between the score
      (sum of grades along all aortic segments) of positive FDG uptake and
      calcification and patient age was analyzed with Spearman rank correlation.
      Comparison of frequency of FDG uptake and calcification with age, sex, risk
      factors for cardiovascular disease (CVD), or history of CVD was performed with
      chi2 analysis. RESULTS: Fifty patients had at least one area of FDG uptake in
      thoracic aortic wall, 14 of whom showed focal FDG uptake. Intermediate to intense
      FDG uptake tended to be observed in the descending aorta. Forty-five patients had
      at least one measurable aortic calcification. Thick calcification was observed
      most often at the aortic arch. Twelve patients had 13 uptake areas at the
      calcification site. Patients with positive findings were on average older (P <.05
      for both increased uptake and calcification); the older patient group had higher
      frequency of both aortic wall uptake (P <.005) and calcification (P <.001). The
      calcification score correlated with age (rho = 0.60, P <.001) but the FDG uptake
      score did not. Women, patients with hyperlipidemia, and patients with history of
      CVD tended to show increased FDG uptake (P =.073,.080, and.068, respectively),
      whereas patients with diabetes had significantly more calcifications (P <.05).
      CONCLUSION: PET/CT depicted FDG uptake commonly in the thoracic aortic wall. The
      FDG uptake site was mostly distinct from the calcification site and may possibly
      be located in areas of metabolic activity of atherosclerotic changes.

PMID- 14593194
TI  - MR angiography with gadofosveset trisodium for peripheral vascular disease: phase
      II trial.
AB  - PURPOSE: To evaluate the dose response and safety of gadofosveset trisodium
      enhanced magnetic resonance (MR) angiography compared with nonenhanced two
      dimensional time-of-flight MR angiography and with x-ray angiography as the
      standard. MATERIALS AND METHODS: In this randomized, 20-center, double-blind
      study, 238 men and women who had peripheral vascular disease or were suspected of
      having it received intravenous injection of placebo or gadofosveset (0.005, 0.01,
      0.03, 0.05, or 0.07 mmol per kilogram of body weight). MR angiographic images
      were evaluated by three blinded readers, and x-ray angiographic images were
      evaluated by two readers. Hypothesis testing for the presence of a dose response
      was based on a linear test for trend for increase in area under the receiver
      operating characteristic curve as a function of dose for each reader of MR
      angiographic images independently. RESULTS: Gadofosveset administration resulted
      in a dose-dependent increase in diagnostic accuracy for detection of aortoiliac
      occlusive disease as reflected in the area under the receiver operating
      characteristic curve for each reader (P <.001). The plateau in effectiveness
      improvement began at the 0.03 mmol/kg dose. At doses of 0.03 mmol/kg and higher,
      gadofosveset-enhanced MR angiography provided an approximate 20% increase in
      accuracy over nonenhanced MR angiography for diagnosis of clinically significant
      aortoiliac occlusive disease. Gadofosveset exhibited a good safety profile in all
      dose groups. Three serious adverse events were possibly or probably related to
      gadofosveset administration. There were no dose-related trends in severe or
      serious adverse events in patients receiving gadofosveset. CONCLUSION: A dose of
      0.03 mmol/kg of gadofosveset was safe and effective for evaluation of aortoiliac
      occlusive disease with MR angiography.

PMID- 14593195
TI  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy: MR imaging findings at different ages--3rd-6th decades.
AB  - PURPOSE: To depict various brain lesions that have been described in patients who
      have cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy (CADASIL) with prospective standardized magnetic resonance
      (MR) imaging in patients of different age groups. MATERIALS AND METHODS: Forty
      patients with CADASIL in different age groups (20-30 years, n = 5; 31-40 years, n
      = 4; 41-50 years, n = 16; 51-60 years, n = 15) underwent transverse MR imaging
      with T1-weighted dual fast spin-echo, fluid-attenuated inversion-recovery, and
      T2*-weighted gradient-echo sequences. Images were analyzed by one
      neuroradiologist for the presence of areas of hyperintensity, lacunar infarcts,
      microbleeds, and subcortical lacunar lesions (SLLs) in different anatomic
      locations. Descriptive statistics were obtained for the presence of MR imaging
      abnormalities in various brain areas and for distribution according to age.
      RESULTS: The mean age of the 40 mutation carriers (21 women, 19 men) was 45 years
      +/- 10 (SD). In patients with CADASIL who were 20-30 years old, characteristic
      hyperintense lesions in the anterior temporal lobe (100% [five of five]) and SLLs
      (20% [one of five]) were the only abnormalities seen on MR images. In patients
      who were 30-40 years old, lacunar infarcts were found in 75% (three of four) of
      cases. More areas of hyperintensity were noted, and they frequently involved the
      external capsule, basal ganglia, and brainstem. In patients 41-50 years old,
      microbleeds were observed in 19% (three of 16). In patients older than 50 years,
      areas of hyperintensity (100% [15 of 15]), SLLs (73% [11 of 15]), lacunar
      infarcts (93% [14 of 15]), and microbleeds (47% [seven of 15]) were frequently
      observed. CONCLUSION: The four types of brain lesions that are observed in
      patients with CADASIL were seen in patients of different age groups.

PMID- 14593196
TI  - CT colonography data interpretation: effect of different section thicknesses-
      preliminary observations.
AB  - PURPOSE: To evaluate if differences exist in the interpretation of thin- and
      thick-section reconstructions at computed tomographic (CT) colonography.
      MATERIALS AND METHODS: Twenty-five patients underwent multi-detector row CT
      colonography prior to colonoscopy. CT images were reconstructed with two methods:
      1.25-mm sections reconstructed every 1 mm (thin) and 5-mm sections reconstructed
      every 2 mm (thick). Two independent readers interpreted thin sections, then
      waited a minimum of 15 days before interpreting thick sections. With colonoscopy
      as the reference standard, comparisons were made between interpretation of thin
      and thick sections, including sensitivity, specificity, and number of false
      positive observations. Interpretation times were recorded, and comparisons were
      made by using repeated measures analysis of variance. For all tests, P <.05
      indicated a statistically significant difference. RESULTS: At colonoscopy, 10
      patients had 12 polyps (< or =5 mm, n = 7; 6-9 mm, n = 2; > or =10 mm, n = 3).
      Sensitivity for polyp detection was statistically indistinguishable for thin and
      thick sections. Reader 1 had three false-positive findings with thin sections and
      six with thick sections. Reader 2 had six false-positive findings with thin
      sections and 11 with thick sections. For both readers, the number of false
      positive findings was significantly lower for thin sections than for thick
      sections (P =.035). Specificity was 93.3% with thin sections and 80.0% with thick
      sections for reader 1 and 80.0% with thin sections and 73.3% with thick sections
      for reader 2. Mean interpretation time for reader 1 was significantly longer with
      thin sections (P <.001). Mean interpretation time for reader 2 was 13.0 minutes
      for both thin and thick sections. CONCLUSION: Specificity improved for both
      readers with thin sections, with no difference in sensitivity.

PMID- 14593197
TI  - Endovascular treatment of internal carotid artery stenosis: effect of primary
      stent application on debris particle release in human cadaveric specimens.
AB  - PURPOSE: To compare debris release with primary stent application (self-expanding
      stent application at stenosis and then balloon dilation through the opened stent)
      and that with secondary stent application (balloon angioplasty of stenosis and
      afterward additional stent application) for high-grade internal carotid artery
      stenosis in human cadaveric specimens. MATERIALS AND METHODS: Fresh human
      cadaveric internal carotid artery specimens were attached to a tube system. High
      grade stenoses (>66%) were selected, randomized for primary or secondary stent
      application, and then treated, with fluoroscopic guidance, while the system was
      rinsed in a pulsating flow. Fluid was collected and filtered, and debris
      particles were examined with a light microscope. Particles were analyzed
      according to those consecutively caught by 100 x 100-microm and 11 x 11-microm
      mesh filters. Results were evaluated in relation to stent application. For
      statistical analyses of group differences, the exact Mann-Whitney U test was
      used. RESULTS: Thirteen high-grade human cadaveric internal carotid artery
      stenoses were analyzed. Five specimens were randomly assigned to secondary stent
      application, and eight were assigned to primary stent application. No significant
      difference could be demonstrated for debris release with primary or secondary
      stent application. P values ranged from.051 to.754. CONCLUSION: The reported
      superiority of primary stent application may not be related to debris reduction.

PMID- 14593199
TI  - Reevaluation of human cytomegalovirus coding potential.
AB  - The Bio-Dictionary-based Gene Finder was used to reassess the coding potential of
      the AD169 laboratory strain of human cytomegalovirus and sequences in the Toledo
      strain that are missing in the laboratory strain of the virus. The gene-finder
      algorithm assesses the potential of an ORF to encode a protein based on matches
      to a database of amino acid patterns derived from a large collection of proteins.
      The algorithm was used to score all human cytomegalovirus ORFs with the potential
      to encode polypeptides >/=50 aa in length. As a further test for functionality,
      the genomes of the chimpanzee, rhesus, and murine cytomegaloviruses were searched
      for orthologues of the predicted human cytomegalovirus ORFs. The analysis
      indicates that 37 previously annotated ORFs ought to be discarded, and at least
      nine previously unrecognized ORFs with relatively strong coding potential should
      be added. Thus, the human cytomegalovirus genome appears to contain approximately
      192 unique ORFs with the potential to encode a protein. Support for several of
      the predictions of our in silico analysis was obtained by sequencing several
      domains within a clinical isolate of human cytomegalovirus.

PMID- 14593200
TI  - Extensive repetitive DNA facilitates prokaryotic genome plasticity.
AB  - Prokaryotic genomes are substantially diverse, even when from closely related
      species, with the resulting phenotypic diversity representing a repertoire of
      adaptations to specific constraints. Within the microbial population, genome
      content may not be fixed, as changing selective forces favor particular
      phenotypes; however, organisms well adapted to particular niches may have evolved
      mechanisms to facilitate such plasticity. The highly diverse Helicobacter pylori
      is a model for studying genome plasticity in the colonization of individual
      hosts. For H. pylori, neither point mutation, nor intergenic recombination
      requiring the presence of multiple colonizing strains, is sufficient to fully
      explain the observed diversity. Here we demonstrate that H. pylori has extensive,
      nonrandomly distributed repetitive chromosomal sequences, and that recombination
      between identical repeats contributes to the variation within individual hosts.
      That H. pylori is representative of prokaryotes, especially those with smaller
      (<2 megabases) genomes, that have similarly extensive direct repeats, suggests
      that recombination between such direct DNA repeats is a widely conserved
      mechanism to promote genome diversification.

PMID- 14593198
TI  - The generation and utilization of a cancer-oriented representation of the human
      transcriptome by using expressed sequence tags.
AB  - Whereas genome sequencing defines the genetic potential of an organism,
      transcript sequencing defines the utilization of this potential and links the
      genome with most areas of biology. To exploit the information within the human
      genome in the fight against cancer, we have deposited some two million expressed
      sequence tags (ESTs) from human tumors and their corresponding normal tissues in
      the public databases. The data currently define approximately 23,500 genes, of
      which only approximately 1,250 are still represented only by ESTs. Examination of
      the EST coverage of known cancer-related (CR) genes reveals that <1% do not have
      corresponding ESTs, indicating that the representation of genes associated with
      commonly studied tumors is high. The careful recording of the origin of all ESTs
      we have produced has enabled detailed definition of where the genes they
      represent are expressed in the human body. More than 100,000 ESTs are available
      for seven tissues, indicating a surprising variability of gene usage that has led
      to the discovery of a significant number of genes with restricted expression, and
      that may thus be therapeutically useful. The ESTs also reveal novel nonsynonymous
      germline variants (although the one-pass nature of the data necessitates careful
      validation) and many alternatively spliced transcripts. Although widely exploited
      by the scientific community, vindicating our totally open source policy, the EST
      data generated still provide extensive information that remains to be
      systematically explored, and that may further facilitate progress toward both the
      understanding and treatment of human cancers.

PMID- 14593201
TI  - Solution structure of a de novo protein from a designed combinatorial library.
AB  - Combinatorial libraries of de novo amino acid sequences can provide a rich source
      of diversity for the discovery of novel proteins. Randomly generated sequences,
      however, rarely fold into well ordered protein-like structures. To enhance the
      quality of a library, diversity must be focused into those regions of sequence
      space most likely to yield well folded structures. We have constructed focused
      libraries of de novo sequences by designing the binary pattern of polar and
      nonpolar amino acids to favor structures that contain abundant secondary
      structure, while simultaneously burying hydrophobic side chains in the protein
      interior and exposing hydrophilic side chains to solvent. Because binary
      patterning specifies only the polar/nonpolar periodicity, but not the identities
      of the side chains, detailed structural features, including packing interactions,
      cannot be designed a priori. Can binary patterned libraries nonetheless encode
      well folded proteins? An unambiguous answer to this question requires
      determination of a 3D structure. We used NMR spectroscopy to determine the
      structure of S-824, a novel protein from a recently constructed library of 102
      residue sequences. This library is "naive" in that it has not been subjected to
      high-throughput screens or directed evolution. The experimentally determined
      structure of S-824 is a four-helix bundle, as specified by the design. As
      dictated by the binary-code strategy, nonpolar side chains are buried in the
      protein interior, and polar side chains are exposed to solvent. The polypeptide
      backbone and buried side chains are well ordered, demonstrating that S-824 is not
      a molten globule and forms a unique structure. These results show that amino acid
      sequences that have neither been selected by evolution, nor designed by computer,
      nor isolated by high-throughput screening, can form native-like structures. These
      findings validate the binary-code strategy as an effective method for producing
      vast collections of well folded de novo proteins.

PMID- 14593202
TI  - Allosteric modulation of group III metabotropic glutamate receptor 4: a potential
      approach to Parkinson's disease treatment.
AB  - Parkinson's disease (PD) is a debilitating movement disorder that afflicts >1
      million people in North America. Current treatments focused on dopamine
      replacement strategies ultimately fail in most patients because of loss of
      efficacy and severe adverse effects that worsen as the disease progresses. The
      recent success of surgical approaches suggests that a pharmacological
      intervention that bypasses the dopamine system and restores balance in the basal
      ganglia motor circuit may provide an effective treatment strategy. We previously
      identified the metabotropic glutamate receptor 4 (mGluR4) as a potential drug
      target and predicted that selective activation of mGluR4 could provide palliative
      benefit in PD. We now report that N-phenyl-7-(hydroxylimino)cyclopropa[b]chromen
      1a-carboxamide (PHCCC) is a selective allosteric potentiator of mGluR4. This
      compound selectively potentiated agonist-induced mGluR4 activity in cultured
      cells expressing this receptor and did not itself act as an agonist. Furthermore,
      PHCCC potentiated the effect of l-(+)-2-amino-4-phosphonobutyric acid in
      inhibiting transmission at the striatopallidal synapse. Modulation of the
      striatopallidal synapse has been proposed as a potential therapeutic target for
      PD, in that it may restore balance in the basal ganglia motor circuit. Consistent
      with this, PHCCC produced a marked reversal of reserpine-induced akinesia in
      rats. The closely related analogue 7-(hydroxylimino)cyclopropachromen-1a
      carboxamide ethyl ester, which does not potentiate mGluR4, had no effect in this
      model. These results are evidence for in vivo behavioral effects of an allosteric
      potentiator of mGluRs and suggest that potentiation of mGluR4 may be a useful
      therapeutic approach to the treatment of PD.

PMID- 14593203
TI  - Exploring the functional complexity of cellular proteins by protein knockout.
AB  - Comprehensive dissection of protein functions entails more complicated
      manipulations than simply eliminating the protein of interest. Established
      knockdown technologies, such as RNA interference, antisense
      oligodeoxynucleotides, or ribozymes, are limited for specific applications such
      as modulating protein levels or specific targeting of a posttranslationally
      modified subpopulation. Here we show that the engineered Skp1, Cullin 1, and F
      box-containing betaTrCP substrate receptor ubiquitin-proteolytic system,
      designated protein knockout, could achieve not only total elimination but also
      rapid and systematic reduction of a given cellular protein. Stable expression of
      a single engineered betaTrCP demonstrated simultaneous and sustained degradation
      of the entire retinoblastoma family proteins. Furthermore, the engineered
      betaTrCP was capable of selecting hypo- but not hyperphosphorylated forms of
      retinoblastoma for degradation. The engineered betaTrCP has been extensively
      modified to increase its specificity in substrate selection. This optimized
      protein-knockout system offers a powerful and versatile proteomic tool to dissect
      diverse functional properties of cellular proteins in somatic cells.

PMID- 14593204
TI  - Posttranscriptional control of the competence factor betaFTZ-F1 by juvenile
      hormone in the mosquito Aedes aegypti.
AB  - In anautogenous mosquitoes, vitellogenesis, which includes production of yolk
      protein precursors, requires blood feeding. Consequently, mosquitoes transmit
      many diseases. Understanding the molecular mechanisms of vitellogenesis
      regulation will contribute significantly to vector control strategies. Newly
      emerged Aedes aegypti females require 3 days before becoming competent to
      activate vitellogenesis in response to a blood-meal-initiated, elevated titer of
      20-hydroxyecdysone (20E). An orphan nuclear receptor gene betaFTZ-F1 is
      transcribed in the fat body of newly emerged mosquito females; however, the
      betaFTZ-F1 protein is only found 3 days later. Dramatically increased titer of
      the juvenile hormone III (JH III) is essential for the acquisition of 20E
      competence. In vitro fat body culture experiments have shown that betaFTZ-F1
      protein appears after exposure to JH III. Injection of double-stranded RNA
      complementary to betaFTZ-F1 into newly emerged females attenuated expression of
      the early genes EcR-B, E74B, and E75A and the target YPP gene Vg, in response to
      a blood meal. Thus, betaFTZ-F1 is indeed the factor defining the acquisition of
      competence to 20E in the mosquito fat body. Moreover, this is achieved through JH
      III-mediated posttranscriptional control of betaFTZ-F1.

PMID- 14593205
TI  - Calcium-dependent molecular spring elements in the giant protein titin.
AB  - Titin (also known as connectin) is a giant protein with a wide range of cellular
      functions, including providing muscle cells with elasticity. Its physiological
      extension is largely derived from the PEVK segment, rich in proline (P),
      glutamate (E), valine (V), and lysine (K) residues. We studied recombinant PEVK
      molecules containing the two conserved elements: approximately 28-residue PEVK
      repeats and E-rich motifs. Single molecule experiments revealed that calcium
      induced conformational changes reduce the bending rigidity of the PEVK fragments,
      and site-directed mutagenesis identified four glutamate residues in the E-rich
      motif that was studied (exon 129), as critical for this process. Experiments with
      muscle fibers showed that titin-based tension is calcium responsive. We propose
      that the PEVK segment contains E-rich motifs that render titin a calcium
      dependent molecular spring that adapts to the physiological state of the cell.

PMID- 14593206
TI  - The T cell receptor beta enhancer promotes access and pairing of Dbeta and Jbeta
      gene segments during V(D)J recombination.
AB  - The precise function of cis elements in regulating V(D)J recombination is still
      controversial. Here, we determined the effect of inactivation of the TCRbeta
      enhancer (Ebeta) on cleavage and rearrangement of Dbeta1, Dbeta2, Jbeta1, and
      Jbeta2 gene segments in CD4-CD8- [double-negative (DN)] and CD4+CD8+ [double
      positive (DP)] thymocytes. In Ebeta-deficient mice, (i) Dbeta1 rearrangements
      were more severely impaired than Dbeta2 rearrangements; (ii) most of the Dbeta
      and Jbeta cleavages and rearrangements occurred in DP, rather than in DN,
      thymocytes; and (iii) most of the 3' Dbeta1 cleavages were coupled to 5' Dbeta2
      cleavages instead of to Jbeta cleavages, resulting in nonstandard Dbeta1-Dbeta2
      Jbeta2 joints. These findings suggest that the Ebeta regulates TCRbeta
      rearrangement by promoting accessibility of Dbeta and Jbeta gene segments in DN
      thymocytes and proper pairing between Dbeta1 and Jbeta gene segments for cleavage
      and joining in DP thymocytes.

PMID- 14593207
TI  - Generation of hair cells by stepwise differentiation of embryonic stem cells.
AB  - The increase in life expectancy is accompanied by the growing burden of chronic
      diseases. Hearing loss is perhaps the most prevalent of all chronic diseases. In
      addition to age-related hearing loss, a substantial number of cases of
      audiological impairment are either congenital in nature or acquired during
      childhood. The permanence of hearing loss is mainly due to the inability of the
      cochlear sensory epithelium to replace lost mechanoreceptor cells, or hair cells.
      Generation of hair cells from a renewable source of progenitors that can be
      transplanted into damaged inner ears is a principal requirement for potential
      cell replacement therapy in this organ. Here, we present an experimental protocol
      that enables us to routinely create inner ear progenitors from murine embryonic
      stem cells in vitro. These progenitors express a comprehensive set of marker
      genes that define the developing inner ear, in particular the organ's developing
      sensory patches. We further demonstrate that cells that express markers
      characteristic of hair cells differentiate from embryonic stem cell-derived
      progenitors. Finally, we show that these progenitors integrate into the
      developing inner ear at sites of epithelial injury and that integrated cells
      start expressing hair cell markers and display hair bundles when situated in
      cochlear or vestibular sensory epithelia in vivo.

PMID- 14593208
TI  - Src kinase activation by direct interaction with the integrin beta cytoplasmic
      domain.
AB  - Src tyrosine kinases transmit integrin-dependent signals pivotal for cell
      movement and proliferation. Here, we establish a mechanism for Src activation by
      integrins. c-Src is shown to bind constitutively and selectively to beta3
      integrins through an interaction involving the c-Src SH3 domain and the carboxyl
      terminal region of the beta3 cytoplasmic tail. Clustering of beta3 integrins in
      vivo activates c-Src and induces phosphorylation of Tyr-418 in the c-Src
      activation loop, a reaction essential for adhesion-dependent phosphorylation of
      Syk, a c-Src substrate. Unlike c-Src, Hck, Lyn, and c-Yes bind more generally to
      beta1A, beta2, and beta3 cytoplasmic tails. These results invoke a model whereby
      Src is primed for activation by direct interaction with an integrin beta tail,
      and integrin clustering stabilizes activated Src by inducing intermolecular
      autophosphorylation. The data provide a paradigm for integrin regulation of Src
      and a molecular basis for the similar functional defects of osteoclasts or
      platelets from mice lacking beta3 integrins or c-Src.

PMID- 14593209
TI  - Effects of the vasoactive intestinal peptide (VIP) and related peptides on
      glioblastoma cell growth in vitro.
AB  - The growth rate of numerous cancer cell lines is regulated in part by actions of
      neuropeptides of the vasoactive intestinal peptide (VIP) family, which also
      includes pituitary adenylate cyclase-activating peptide (PACAP), glucagon, and
      peptide histidine/isoleucine (PHI). The aim of this work was to investigate the
      effect of these peptides on the growth of the rat glioblastoma cell line C6 in
      vitro. We also sought to determine which binding sites were correlated with the
      effects observed. Proliferation studies performed by means of a CyQuant trade
      mark assay showed that VIP and PACAP strongly stimulated C6 cell proliferation at
      most of the concentrations tested, whereas PHI increased cell proliferation only
      when associated with VIP. Two growth hormone-releasing factor (GRF) derivatives
      and the VIP antagonist hybrid peptide neurotensin-VIP were able to inhibit VIP
      induced cell growth stimulation, even at very low concentrations. Binding
      experiments carried out on intact cultured C6 cells, using 125I-labeled VIP and
      PACAP as tracers, revealed that the effects of the peptides on cell growth were
      correlated with the expression on C6 cells of polyvalent high-affinity VIP-PACAP
      binding sites and of a second subtype corresponding to very high-affinity VIP
      selective binding species. The latter subtype, which interacted poorly with PACAP
      with a 10,000-fold lower affinity than VIP, might mediate the antagonist effects
      of neurotensin- VIP and of both GRF derivatives on VIP-induced cell growth
      stimulation.

PMID- 14593210
TI  - Increased gene expression of beta-1,4-galactosyltransferase I in rat injured
      sciatic nerve.
AB  - During neurite outgrowth on basal lamina, cell-surface beta-1,4
      galactosyltransferase I (beta-1,4-GalT-I) functions as one of the receptors of
      laminin by binding to N-linked oligosaccharides on the laminin E8 domain. In the
      present study, it was revealed that in rat injured sciatic nerves, the expression
      of beta-1,4-GalT-I mRNA reached its peak 2-3 d after axotomy in both proximal and
      distal stumps, and decreased thereafter as demonstrated by Northern blot
      analysis. In situ hybridization revealed that beta-1,4-GalT-I mRNAmainly
      localized in Schwann cells of the injured nerves. Moreover the Galbeta1-4GlcNAc
      (N-acetylglucosamine) group mainly localized in Schwann cells of the injured
      nerves by Ricinus communis agglutinin-I (RCA-I) lectin histochemistry. However,
      the changes in abundance of the Galbeta1-4GlcNAc group in injured nerves were not
      consistent with the expression of beta-1, 4-GalT-I mRNA. These findings indicate
      that beta-1,4-GalT-I might be involved in the regeneration of injured peripheral
      nerves at the early injury stage.

PMID- 14593211
TI  - Hypertonicity promotes survival of corticospinal motoneurons via mitogen
      activated protein kinase p38 signaling.
AB  - Extracellular hypertonicity can induce the phosphorylation of mitogen-activated
      protein kinases (MAPKs). Of these, both extracellular signal-regulated kinases
      (ERKs) and the stress-activated kinase p38 have been implicated in neuronal cell
      survival. Resuscitation with hypertonic saline decreases secondary brain injury
      after trauma, as well as neuronal damage, after ischemia. Since hypertonicity has
      been shown to support somatic cell survival, we investigated if hypertonicity can
      also prevent neuronal cell death via MAPK signaling. Death of postnatal rat
      corticospinal motoneurons (CSMNs) was induced by serum deprivation, and survival
      in both isotonic and hypertonic media was assessed after 20 h. Addition of NaCl
      (4-250 mM) to isotonic medium significantly and dose dependently protected CSMN
      in enriched cultures, increasing cell survival by up to 70% over that in isotonic
      medium. This response was not restricted to NaCl; addition of KCl, choline
      chloride, and sucrose had similar effects on cell survival. In addition,
      hypertonicity supported the survival of pure CSMN populations, albeit with lower
      potency. In cortical cell suspensions, hypertonic NaCl (20-100 mM) increased
      basal phosphorylation of p38 and ERK. The activation of both MAPKs, which was
      induced by 40 mM NaCl, was transient. Cultivation of CSMNs in media containing
      the specific p38 inhibitor SB203580 abolished the protective effect of hypertonic
      NaCl, indicating a central role for p38. We therefore conclude that hypertonicity
      can prevent neuronal cell death via MAPK signaling.

PMID- 14593212
TI  - Induction of neuron-specific enolase promoter and neuronal markers in
      differentiated mouse bone marrow stromal cells.
AB  - Mesenchymal stem cells in the adult bone marrow are differentiated to connective
      tissue, muscle, bone, cartilage, and fat cells. Recent studies in cultures,
      animal models, and humans demonstrated the plasticity of these cells and their
      capacity to express neuronal markers. However, questions were raised as to
      whether the neuronal phenotypes reflect transient changes or even fusion with
      neurons. In this study, we induced the differentiation of mouse stromal cells to
      neuron-like cells and observed the activation of the tissue-specific promoter of
      neuron-specific enolase (NSE). We used transgenic (Tg) mice that carry the
      antiapoptotic human bcl-2 gene, expressed only in neurons under the NSE promoter.
      Some previous studies have indicated that the transgene induces neuroprotection
      in various animal models of neurodegenerative diseases. We found that following
      induction, the mouse stromal cells demonstrate neuronal phenotype and express the
      neuronal marker, NeuN (neural nuclei protein). However, most of the stromal cells
      derived from the Tg mice, but not the wild type, also expressed human Bcl-2, as
      indicated by immunocytochemistry. Furthermore, these induced neuron-like cells
      were more resistant to cell death induced by dopamine. In conclusion, our
      experimental models showed that stromal cells might be induced to neuronal
      phenotypes and activate neuronal-specific promoters. Moreover, neurons targeted
      over expression of the human bcl-2 gene and provided high resistance against such
      apoptotic insults. This novel strategy reveals a new horizon in the improvement
      of gene therapy, based on stem cell transplantation in neurodegenerative
      diseases.

PMID- 14593213
TI  - Expression profiles of PER2 immunoreactivity within the shell and core regions of
      the rat suprachiasmatic nucleus: lack of effect of photic entrainment and
      disruption by constant light.
AB  - The circadian clock cells of the mammalian suprachiasmatic nucleus (SCN) generate
      oscillations in physiology and behavior that are synchronized (entrained) by the
      external light/dark (LD) cycle. The mechanisms that mediate the effect of light
      on the core molecular mechanism of the clock are not well understood, but
      evidence suggests that the Period2 gene, which encodes a key clock regulator
      (PER2), might be involved. We assessed the expression of PER2 immunoreactivity in
      the retinorecipient core and shell compartments of the SCN of rats entrained to
      cycles of discrete light pulses presented at the early subjective day (dawn) or
      night (dusk), or housed in constant light. We found that in animals entrained to
      a 0.5 h:23.5-h LD cycle (light falls near dawn), PER2 expression is rhythmic both
      in the shell and in the core regions of the SCN and indistinguishable from that
      seen in the SCN of control rats housed in complete darkness. Similarly, the
      pattern of PER2 expression in the SCN of rats entrained to a 0.5-h:25.5-h LD
      cycle (light falls near dusk) resembled that in dark-housed controls. We also
      found that presentation of a discrete light pulse in the early subjective night
      did not induce PER2 protein expression in the SCN, even 6 h after photic
      stimulation. Finally, in constant light-housed, behaviorally arrhythmic rats,
      PER2 expression in the SCN was low and nonrhythmic. These results show that
      rhythmic PER2 expression occurs both in the shell and core regions of the rat
      SCN. Furthermore, they show that the expression of PER2 in the SCN is not
      regulated by entraining light. Finally, constant light-induced behavioral
      arrhythmicity is associated with a disruption of rhythmic PER2 expression in the
      whole SCN. Together, the results are consistent with a proposed role for PER2 in
      the core mechanism of the circadian clock but argue against an important role for
      PER2 in the mechanism mediating photic entrainment.

PMID- 14593214
TI  - Neuregulin-1 isoforms are differentially expressed in the intact and regenerating
      adult rat nervous system.
AB  - Our knowledge on Neuregulin-1 (Nrg-1) during development of the nervous system is
      increasing rapidly, but little is known about Nrg-1-ErbB signaling in the adult
      brain. Nrg-1 is involved in determination, proliferation, differentiation, and
      migration of neurons and glial cells in the developing brain. In the peripheral
      nervous system, Nrg-1 signaling is required for Schwann cell differentiation and
      myelination, and establishment of neuromuscular junctions (NMJs). Multiple
      alternative splicing of Nrg-1 was shown, but correlation of its structural and
      functional diversity was rarely addressed. Therefore, we investigated the
      expression of Nrg-1 isoforms in the rat brain and brain-derived cell types, and
      their involvement in regeneration of the adult brain, using immunohistochemistry,
      in situ hybridization, and semiquantitative RT-PCR. We found expression of at
      least 12 distinct Nrg-1 isoforms in the brain and altered expression of several
      isoforms in the facial motor nucleus after peripheral transection of the seventh
      cranial nerve. An upregulation of Nrg-1 type-I mRNA, probably type- I-alpha, was
      observed in reactive astrocytes of the facial nucleus 1 d postaxotomy. Nrg-1 type
      III and the splice variants beta1 and beta5 are dramatically downregulated in
      axotomized motoneurons, which lack contact to their target tissue. Baseline
      expression levels were reestablished when the first axons reached the facial
      muscles and reformed NMJs. Nrg-1-beta1 and -beta5 might act in maintenance of
      NMJs. The splice variants beta2 and beta4 display an initial downregulation of
      mRNA levels, followed by an increase during the period of axon remyelination.
      Thus, Nrg- 1-beta2 and -beta4 might be involved in myelination.

PMID- 14593215
TI  - TNF-alpha and TNF-beta gene polymorphisms in cerebral infarction.
AB  - Tumor necrosis factor (TNF) is an important cytokine in the inflammation process
      of atherosclerosis. Two biallelic polymorphisms in the TNF-alpha (TNF-alpha -308)
      and TNF-beta (TNF-beta +252) genes have been reported to be associated with TNF
      production and susceptibility to inflammatory diseases. We investigated two
      genetic polymorphisms in the TNF locus (TNF-alpha -308 G-->A and TNF-beta +252 A-
      >G) as risk factors for cerebral infarction (CI) by determining its prevalence in
      294 survivors of CI, and in 581 age-, gender-, and race-matched controls. A
      significant association was found for the TNF-alpha and TNF-beta genotypes in CI
      patients compared with controls. A significant increase was found for the TNF
      alpha A allele in controls compared with CI patients (chi2 = 7.593, p = 0.006,
      odds ratio = 1.74, confidence interval = 1.17-2.59). In addition, the TNF-alpha
      GG genotype increased the relative risk for CI in subjects with the TNF-beta AA
      genotype (chi2 = 4.998, p = 0.025). As a result, compared to controls, the
      frequency of the TNF-alpha AA genotype was decreased, whereas that of TNF-beta AA
      was increased in CI patients. The former implies an association with resistance,
      whereas the latter suggests an association with susceptibility to the disease.
      These results show that the TNF-alpha -308 and TNF-beta +252 locus plays an
      important role in the etiopathogenesis of CI.

PMID- 14593216
TI  - Upregulation of p55 and p75 receptors mediating TNF-alpha transport across the
      injured blood-spinal cord barrier.
AB  - Tumor necrosis factor (TNF-alpha) is involved in the inflammation and tissue
      regeneration occurring after spinal cord injury (SCI). This study tests the
      specific role of p55 and p75 receptors in mediating the transport of TNF-alpha
      across the blood-spinal cord barrier (BSCB) after SCI by compression.
      Transcytosis of 125I-TNF-alpha across a monolayer of the cerebral endothelial
      cells that compose the blood-brain barrier was significantly reduced in the
      absence of functional p55 and p75 receptors. At 3 d after SCI, double receptor
      knockout mice had a significantly reduced increase in TNF-alpha uptake from blood
      to injured lumbar spinal cord as compared with their inbred controls, despite the
      similar extent of BSCB disruption (measured by 99mTc-albumin). The p75 single
      receptor knockout mice had a reduced increase in 125I-TNF-alpha uptake, whereas
      the p55 receptor knockout mice had no significant increase of 125I-TNF-alpha
      uptake after SCI, suggesting that the p55 receptor plays a major role. Hence, the
      increased uptake of TNF-alpha 3 d after SCI is not explained by nonspecific
      barrier disruption but by receptor-mediated upregulation of transport.
      Quantitative RT-PCR analysis further showed that upregulation of TNF-alpha
      transport was related to increased expression of mRNA for p55 and p75 receptors.
      The increase of p55 receptor expression was more robust and seen between 12 h and
      1 wk after SCI, whereas the increase of p75 receptor expression occurred later
      and involved fewer regions. Thus, the differential upregulation of p55 and p75
      receptors indicates that permeation of TNF-alpha across the injured BSCB remains
      a regulated process. Knowledge of receptor-mediated regulation could facilitate
      effective therapeutic manipulation of BSCB permeation of vascular cytokines
      important to CNS regeneration.

PMID- 14593218
TI  - Sick autonomy.
AB  - Complex social and economic forces have placed patient autonomy at the center of
      medical ethics, and thereby displaced an older ethic of physician beneficence.
      This development arose, and is sustained, by waning trust in the traditional
      doctor-patient relationship. As patients have increasingly become clients and
      consumers, a contract basis for medical care has put the ancient covenant of care
      in jeopardy. Here, a philosophical approach to harmonize the apparent conflicting
      claims of patient autonomy and physician beneficence is offered by demonstrating
      that autonomy need not be understood as protecting a threatened identity. If
      persons are regarded as atomistic, certain defensive notions of individualistic
      rights-based autonomy prevail; if a relational construction of personal identity
      is employed instead, then respect for autonomy becomes part of a wider morality
      of relationship and care. By reconfiguring trust within this latter understanding
      of personhood, bioethics better balances its concerns over choices and actions
      with those of relationship and responsibility. Neither atomistic autonomy nor the
      ethics of responsibility can claim hegemony, for they are mutually
      interdependent, and a complete account of medicine's moral axis requires that
      they be integrated. This reorientation is crucial for reasserting the ethos of
      clinical medicine, whose fundamental mandate remains the care of others.

PMID- 14593217
TI  - Getting the numbers right: statistical mischief and racial profiling in heart
      failure research.
AB  - The claim that blacks die from heart failure at a rate twice that of whites is
      informing efforts to develop and market the drug BiDil, which is currently
      undergoing clinical trials to be approved by the FDA as the first drug ever
      specified to treat African Americans--and only African Americans--for heart
      failure. The drug and its companion statistic have since come to play prominent
      roles in debates about so-called "racial profiling" in medicine and the
      legitimacy of using social categories of race in biomedical research.
      Nonetheless, this statistic is wrong. The most current data available place the
      black:white mortality ratio for heart failure at approximately 1.1:1. The article
      tells the story of attempts to get to the source of the supposed 2:1 mortality
      ratio and explores some of the implications of the acceptance of these erroneous
      data, both for the allocation of resources to combat disease and for our broader
      understanding of the nature and meaning of race.

PMID- 14593219
TI  - Individual good and common good: a communitarian approach to bioethics.
AB  - The field of bioethics emerged in the late 1960s and early 1970s. Among its early
      issues were the protection of human research subjects, the rights of patients,
      abortion, and reproductive issues. Partly as a reflection of the times, and of
      those issues, the field became focused on autonomy and individual rights, and
      liberal individualism came to be the dominant ideology in the 1980s and 1990s.
      Communitarianism, as an alternative ideology focused more on the common good and
      the public interest than on autonomy, was a neglected approach. But many
      bioethical issues can not reasonably be reduced to questions of individualism and
      choice only. Issues of genetics and reproduction will of necessity touch on the
      society as a whole, its values, and its social institutions. Serious ethical
      analysis must take the social implications seriously and not simply assume that
      they should be left to autonomous choices of individuals. Human beings are social
      animals and our nature is distorted if we think of ourselves only as co-existing
      social atoms. Various approaches to communitarianism are outlined, and the
      question of the relationship between individual good and common good is
      confronted.

PMID- 14593220
TI  - Repeat participation among normal healthy research volunteers: professional
      guinea pigs in clinical trials?
AB  - The recent death of a normal healthy volunteer, as well as the increased use of
      normal volunteers as research subjects, has heightened the attention given to the
      participation of normal volunteers in clinical research. An overlooked sub
      population of normal healthy volunteers are repeat, veteran volunteers. This
      essay discusses ethical and methodological issues associated with the use of
      repeat volunteers in research, along with existing guidelines regarding the use
      of repeat healthy volunteers, and concludes with recommendations for safeguarding
      repeat volunteers and ideas supporting centralized recruiting.

PMID- 14593221
TI  - The maligning of a country doctor.
AB  - This article traces the misidentification of the subject of an illustration in a
      text about women and illness in the 19th century.The heroic efforts of surgical
      pioneer Ephraim McDowell (1771-1830) and his brave patient Jane Todd Crawford are
      returned to their rightful place in medical history.

PMID- 14593222
TI  - Prophet in his own country: Carlos Chagas and the Nobel Prize.
AB  - In 1909, Carlos Chagas (1878-1934) discovered a new protozoon, Trypanosoma cruzi,
      and the (previously unknown) disease that it causes. Within a few months,
      virtually single-handed, he described the pathogen, its vector, and the clinical
      features of American trypanosomiasis (Chagas disease), a feat unique in medical
      history. He headed the Oswaldo Cruz Institute after the death of its founder
      (1917) until his own death; and from 1920 until 1926 he also directed the
      Brazilian Department of Public Health. His discovery brought him worldwide
      acclaim, but at home antagonism against Chagas, muted for years, finally flared
      up in a campaign that was acted out in the 1921-22 plenary sessions of the
      National Academy of Medicine. Chagas's name was repeatedly proposed for the Nobel
      Prize but he never received it; this hostile campaign may have been instrumental
      in costing him the award.

PMID- 14593223
TI  - The rise of peptic ulcer, 1900-1950.
AB  - The seeming increase in the incidence of peptic ulcer after 1900 quickly occupied
      the attention of physicians. Their understanding and treatment of peptic ulcer
      was shaped not only by new diagnostic tools, but by differences between
      contesting medical specialties, broad concepts or paradigms current in the larger
      medical and scientific community, and prevailing social and ideological beliefs.
      Surgeons and internists, for example, were often at odds over appropriate
      therapies; each maintained that personal experiences demonstrated the efficacy of
      their therapies. Nor were etiological theories derived from empirical data. The
      claim that peptic ulcer resulted from focal infections was simply a reflection of
      the popularity of germ theory. Other explanations included the role of stress,
      race, constitutional makeup, psychosomatic factors, and the pressures of modern
      industrial society. Virtually all were derivative and reflected social and
      intellectual currents that were common in the larger society of which medicine
      was but a part. Thus, the history of peptic ulcer during the first half of the
      20th century provides an instructive and in many ways a typical case study in the
      complexities posed by the emergence of modern medicine.

PMID- 14593224
TI  - Health care in the borderland.
AB  - For over 30 years, Hidalgo County, a geographically isolated and financially
      stressed community in the southwestern corner of New Mexico, has struggled to
      develop a stable primary health care service.The retirement of the county's
      general practitioner in the 1970s was followed by several decades of misses, near
      misses, and out-and-out failures, when the community found it difficult to
      attract and impossible to keep a physician. In order to organize and fund a
      stable medical clinic, the community had to adapt to the realities of a new era
      in medicine. Primary care physicians in rural communities need access to medical
      information and to specialists, help in coping with the economic pressures of
      medical care, and support that will enable them to develop a sustainable
      lifestyle. Hidalgo County now has a modern health care delivery system. The
      experiences that led to the creation of the present clinic provide insight into
      the problems for the delivery of primary health care in remote areas and suggest
      solutions that may be relevant to other communities across rural America.

PMID- 14593225
TI  - College physical education: an unrecognized agent of change in combating
      inactivity-related diseases.
AB  - Physical activity patterns during the young adult years are likely to be
      important influences on habitual physical activity during overall adult life and,
      consequently, have significant implications for long-term health outcomes. The
      potential reach and impact of college physical education on the promotion of
      physical activity to a large segment of the American population has been largely
      unrecognized. Over the last generation, many colleges and universities have
      reduced or eliminated their physical education requirements. Nonetheless,
      physical education can make important contributions in the primary prevention of
      inactivity-related chronic diseases and to the general education of the college
      student. Awareness and advocacy are needed to strengthen college physical
      education programs.

PMID- 14593226
TI  - Mold: "tsara'at," Leviticus, and the history of a confusion.
AB  - The noun tsara'at appears about two dozen times in the Hebrew Bible, almost
      exclusively in Leviticus, where it is used to describe a state of ritual
      defilement manifested as a scaly condition of the skin, a condition of cloth,
      leather, and the walls of houses. In the Septuagint, the Greek translation of the
      Hebrew Bible, negac tsara'at was translated as aphe lepras; in the Latin Vulgate,
      this became plega leprae. These words in Greek and Latin implied a condition that
      spread over the body, not a term of ritual impurity. Tsara'at has continued to be
      translated as "leprosy," even though this term is not appropriate, as there was
      no leprosy as we know it in the Middle East during the time period the Hebrew
      Bible was written. Others have suggested that the proper translation of tsara'at
      is "mold." The recent identification of a specific mold (Stachybotrys sp.) that
      contaminates buildings and causes respiratory distress, memory loss, and rash,
      and the fact that mold has been present for millennia, lend support to the
      translation of tsara'at as "mold."

PMID- 14593228
TI  - Linomide and antibody-targeted superantigen therapy abolishes formation of liver
      metastases in mice.
AB  - Hematogenous spread of tumor cells and metastasis formation in the liver are
      insidious aspects of cancer progression and are not frequently amenable to
      curative treatment. We examined the effect of Linomide and antibody-targeted
      therapy against the formation of hepatic metastases in vivo. For this purpose,
      syngenic B16 melanoma cells transfected with GA733-2 (a human colon cancer cell
      surface antigen) were injected into a mesenteric vein of C57/Bl6 mice. To test
      bacterial superantigen (Sag) targeting for immunotherapy of liver metastases, we
      used genetically fused proteins consisting of SEA and a Fab moiety of a GA733-2
      tumor-reactive antibody (C215Fab-SEA). Linomide dose-dependently reduced hepatic
      metastases, and at 300 mg/kg this reduction was more than 80%. Treatment with
      C215Fab-SEA decreased metastases formation by 49% and the combination of Linomide
      and C215Fab-SEA was found to completely abolish liver metastases (>99%
      reduction). Taken together, our novel data suggest that Linomide and antibody
      targeted superantigen therapy individually markedly reduce and together abolish
      liver metastases. Considering that current therapy of hepatic metastases is
      mainly limited to surgical resection in a subgroup of patients, these findings
      indicate that Linomide alone or in combination with antibody-targeted
      superantigen may provide a novel approach against liver metastases.

PMID- 14593229
TI  - Receptor-mediated biphasic alteration of hepatocellular transport from hepatocyte
      to bile canaliculi as measured by near-infrared spectroscopy: a novel test with
      glucagon for biliary excretion.
AB  - As glucagon is known to cause a receptor-mediated increase in intracellular
      calcium and cyclic AMP, we have developed a novel method of evaluating the
      integrity of the signal transduction and transport system using glucagon-induced
      changes in indocyanine green (ICG) excretion. The kinetics of the hepatocellular
      concentration of ICG at 4-second intervals was analyzed by near-infrared
      spectroscopy in vivo on the liver surface. After intravenous injection of 0.5
      mg/kg ICG to rabbits, absorbance of ICG increased and then decreased according to
      the two-compartment model: ICG(t) = -Aexp(-alphat) + Bexp(-betat), where alpha
      and beta (min(-1)) indicate the time constants of uptake and excretion,
      respectively. During the excretion phase, 40 microg/kg glucagon was infused as a
      bolus via the portal vein. A biphasic acceleration and retardation of ICG
      excretion from the baseline exponential decay was observed in the controls. In
      order to perturb the glucagon response, colchicine, ouabain, wortmannin and an
      ischemia-reperfusion insult were employed. Colchicine, ouabain and wortmannin
      abolished the biphasic acceleration and retardation of ICG excretion. Glucagon
      response was absent upon the ischemia-reperfusion insult. The observed biphasic
      response to glucagon clearly indicates that glucagon modulates bile canalicular
      contraction and peristalsis via the two glucagon receptors and these second
      messengers. The glucagon response requires the integrity of signal transduction,
      cytoskeleton structure, myosin function, and bile canalicular pump.

PMID- 14593230
TI  - Prevention of peritoneal carcinomatosis from human gastric cancer cells by
      adjuvant-type intraperitoneal immunotherapy in a SCID mouse model.
AB  - PURPOSE: We analyzed the effect of intraperitoneal immunotherapy in an animal
      model mimicking locoregional dissemination of tumor cells during resection of
      advanced tumors. METHODS: We first established a tumor model with human gastric
      cancer cells (MKN-45) in the peritoneal cavity of CB-17-SCID mice. Three hours
      following the injection of tumor cells into the peritoneal cavity, mAb 17-1A
      alone and in combination with human LAK cells were given intraperitoneally at
      different dosages. The results were quantified by determining the weight of the
      peritoneal tumor masses. RESULTS: After intraperitoneal administration of 17-1A
      mAb, a tumor reduction could be shown (median tumor mass after 10 microg mAb: 171
      microg; after 100 microg: 130 microg) when compared with the control group (632
      microg). Following a combined therapy with mAb and LAK cells, a statistically
      significant tumor reduction could be observed (after 10 microg mAb + 20-50 x
      10(6) LAK cells: 80 microg; after 100 microg mAb + 20-50 x 10(6) LAK cells: 12
      microg, p = 0.0005). With specific dosages of antibody and LAK cells it was even
      possible to achieve complete tumor clearance. CONCLUSIONS: Intraperitoneal
      immunotherapy reduces the peritoneal tumor masses and can even prevent the
      peritoneal carcinomatosis formation.

PMID- 14593231
TI  - Minilaparotomy may be independently associated with reduction in inflammatory
      responses after resection for colorectal cancer.
AB  - OBJECTIVES: A minilaparotomy approach (skin incision less than 7 cm) to resection
      of colon cancer is technically feasible, but objective data supporting its
      benefit are scarce. The aim of this study was to clarify whether minilaparotomy
      is independently associated with a reduction in the acute inflammatory response
      after resection of colorectal cancer. DESIGN: Thirty-one patients who underwent
      surgical resection of colorectal cancer using minilaparotomy or conventional
      laparotomy were included in this nonrandomized prospective study. Inflammatory
      responses were evaluated with serum interleukin-6 (IL-6) and C-reactive protein
      (CRP) levels. RESULTS: In both the minilaparotomy and conventional laparotomy
      groups, serum IL-6 and CRP levels significantly increased 24 h after the
      operation (1POD) compared to preoperative levels (p < 0.0001 and p < 0.0001,
      respectively). Median serum levels of IL-6 and CRP in the minilaparotomy group
      were significantly lower at 1POD versus the conventional group (p = 0.0066 and p
      = 0.0033, respectively). Multivariate analyses showed that a smaller increase in
      serum IL-6 or CRP levels at 1POD [less than 75th percentile (112.9 or 10.6 mg/ml,
      respectively)] was independently related to only minilaparotomy. CONCLUSIONS:
      These data in this nonrandomized trial suggest that minilaparotomy may be
      independently associated with reduced inflammatory responses in colorectal cancer
      resection.

PMID- 14593232
TI  - Distance of cecum ligated influences mortality, tumor necrosis factor-alpha and
      interleukin-6 expression following cecal ligation and puncture in the rat.
AB  - BACKGROUND/AIM: A mainstay of laboratory research into new therapies for sepsis
      has been the cecal ligation and puncture (CLP) model in rodents. Previous data
      indicate that the number of punctures made in the cecum and needle size utilized
      are primary determinants of mortality. Despite this, variability exists in
      mortality from this model, even when needle size is held constant. The aim of the
      present study was to evaluate the influence of the length of cecum ligated,
      independent of needle size, as a determinant of mortality. MATERIALS AND METHODS:
      We evaluated this by ligating various cecal lengths in male Sprague-Dawley rats.
      A double puncture was then made with a 20-gauge needle, and mortality was
      analyzed. Plasma TNF-alpha and IL-6 expression was assessed at 6 h. Animals
      received no antibiotics, were not fasted, and fluid resuscitation was
      administered. RESULTS: We determined that mortality does not begin to occur until
      a distance of >5% of cecal length is ligated. Further, our findings indicate that
      in this model, 90-100% mortality occurs 4 days following CLP when a distance of
      >30% is ligated. TNF-alpha and IL-6 expression is markedly increased with
      increasing length of cecum ligated. CONCLUSIONS: Our data demonstrate that the
      length of cecum ligated is a major determinant of mortality in the CLP model of
      sepsis. These findings indicate that investigators must rigorously control the
      distance of the cecum ligated in order to generate consistent mortality and
      inflammation data when utilizing the CLP model in rats. Further, the mortality
      from this model can be adjusted to fit the individual needs of a particular
      experiment.

PMID- 14593233
TI  - Serum and drainage fluid vascular endothelial growth factor levels in early
      surgical wounds.
AB  - BACKGROUND: Wound healing relies on a coordinated expression and release of
      growth factors controlling angiogenesis. We measured vascular endothelial growth
      factor (VEGF) levels in serum and early wound fluid following primary sutured and
      mesh repair of abdominal hernias. MATERIALS AND METHODS: Thirty-seven patients
      were studied measuring serum and wound drainage fluid VEGF by enzyme-linked
      immunosorbent assay preoperatively and on the 1st, 3rd, 5th and 7th postoperative
      days. RESULTS: Serum and wound fluid VEGF levels increased significantly by the
      3rd postoperative day and continued to rise during the conduct of the study with
      wound fluid concentrations always exceeding serum levels. The kinetics of VEGF
      increases were similar in both types of hernia repair; however, serum and wound
      levels rose slightly earlier in the mesh repair group. CONCLUSIONS: Steadily
      increasing levels of VEGF are detected during the early proliferative phase of
      wound healing in both serum and wound fluid. It is unknown whether either is
      predictive for delayed hernia recurrence.

PMID- 14593234
TI  - Persistent extracellular matrix remodelling at the interface to polymers used for
      hernia repair.
AB  - On the one hand, recurrence rates and postoperative complications following
      hernia repair are supposed to be influenced by the kind of mesh material used. On
      the other hand, an impaired collagen metabolism and cleavage within connective
      tissue has been suggested as decisive factor in the pathogenesis of recurrent
      hernia formation. The aim of our study was, therefore, to analyze the impact of
      commonly used mesh materials on quality of collagen deposition, expression of
      collagenases (matrix metalloproteinases; MMP-1/MMP-13), and specific tissue
      inhibitors of MMPs (TIMPs) in an animal study. Four different mesh materials were
      used (Prolene = polypropylene, Mersilene = polyester, and Vypro and Vypro II =
      combinations of polypropylene and polyglactin) and implanted as abdominal wall
      replacement in 60 male Wistar rats. Mesh samples were explanted after 3, 21, and
      90 days and investigated using immunohistochemistry (expression of MMP-1/MMP-13
      and TIMP-1) and cross-polarization microscopy (percentage of collagen type III to
      overall collagen). Besides an insufficient collagen composition with an increased
      percentage of collagen type III, we found a complex expression of collagenases
      and their inhibitors combined with a persistent chronic foreign-body reaction
      even 90 days after implantation. Except for TIMP-1 expression, which was
      significantly related to a lowered amount of inflammatory (r = -0.980, p = 0.02)
      and connective tissue formation (r = -0.951, p = 0.049), there was no relation to
      the expression of collagenases (MMP-1/MMP-13) with regard to the amount of
      inflammatory and connective tissue formation despite partly significant
      differences between implanted polymers.

PMID- 14593235
TI  - Transarterial chemoembolization of advanced liver metastases of neuroendocrine
      tumors--a retrospective single-center analysis.
AB  - BACKGROUND: In neuroendocrine tumors, metastases are a negative prognostic factor
      for survival and quality of life. Transcatheter arterial chemoembolization (TACE)
      is thought to be an effective symptomatic and antiproliferative treatment in
      patients with otherwise progressive disease. METHODS: 62 chemoembolization
      procedures in 26 patients with progressive neuroendocrine tumors were reviewed.
      The underlying disease was carcinoid syndrome in 10, non-functional midgut tumor
      in 2, non-functional pancreatic tumor in 7, malignant insulinoma in 2 patients,
      non-functional tumor of the stomach in 1 and of unknown origin in 4 patients.
      Tumor burden of the liver was <25% in 3, 25-50% in 11, 50-75% in 6 and >75% in 6
      patients. RESULTS: TACE was technically successful in 57 cases. Four patients
      developed minor and 5 major complications. The 30-day mortality rate was 7.7%.
      According to WHO criteria, 14 patients had no change in tumor burden, 2 had
      regression and 5 progress after chemoembolization. Patients with a tumor burden
      >75% of the liver did not benefit from TACE due to the development of major
      complications, whereas patients with low (<50%) tumor burden and high (>50%)
      lipiodol uptake showed a trend towards longer survival. Five-year survival time
      after diagnosis was 48%. Patients treated with octreotide and/or alpha-interferon
      had no benefit from chemoembolization with regard to their carcinoid syndrome.
      CONCLUSIONS: In this retrospective study, patients with low (<50%) tumor burden
      and high (>50%) lipiodol uptake responded better to TACE than end-stage patients.

PMID- 14593236
TI  - Gastrointestinal symptoms in type 1 diabetic patients, as compared to a general
      population. A questionnaire-based study.
AB  - OBJECTIVES: To examine the prevalence of gastrointestinal (GI) symptoms in
      patients with type 1 diabetes as compared to age- and sex-matched controls.
      METHOD: 395 patients with type 1 diabetes, registered at the diabetes outpatient
      unit at the Sahlgrenska University Hospital, were studied by use of a GI symptom
      questionnaire. They were randomly selected within 10-year age intervals from 20
      to 69 years. Age- and sex-matched controls (n=242) were sampled from a cohort
      recruited from the general population. RESULTS: While the study populations were
      well matched with regard to age, sex and body mass index (BMI), the diabetic
      population comprised more smokers and reported symptoms of respiratory and
      ischemic heart disease more frequently. Symptoms of heartburn, acid
      regurgitation, nausea and vomiting were significantly more frequent and intense
      in the diabetic cohort. The occurrence of GI symptoms co-varied with the presence
      of respiratory and cardiac symptoms but was not predicted by age, glycosylated
      haemoglobin (HbA1c) levels or the presence of peripheral neuropathy. CONCLUSION:
      Patients with diabetes type 1 had more frequent and intense upper and lower GI
      symptoms than age- and sex-matched controls, especially if only moderate and
      severe symptoms were considered. The presence of symptoms was related to
      lifestyle factors but not to the degree of diabetes control as expressed by the
      level of HbA1c and the presence of peripheral neuropathy.

PMID- 14593237
TI  - Abnormal umbilical artery Doppler waveforms and cord blood inhibin a and inhibin
      B levels.
AB  - Inhibin A and inhibin B are glycoprotein hormones produced by human placenta and
      by several fetal organs during pregnancy. They are secreted in maternal
      circulation in increasing amounts from early until term pregnancy, and in
      umbilical cord blood levels are significantly lower than in maternal serum and do
      not differ from mid-pregnancy to term gestation. In the present study, we aimed
      to determine whether secretion of inhibin A and inhibin B into the fetal
      circulation is increased in pregnancies complicated by umbilical-placental
      vascular insufficiency. A group of women (n = 13) with abnormal Doppler umbilical
      artery flow velocimetry and a group of control women (n = 11) with uncomplicated
      term pregnancies and normal umbilical artery flow velocity waveforms were
      studied. In each woman, inhibin A and inhibin B concentrations were estimated in
      umbilical cord artery and vein. In the two groups of women, mean inhibin A levels
      did not differ between umbilical cord artery and vein. In addition, no difference
      was retrieved both in umbilical cord artery and vein values between healthy
      controls and patients with abnormal Doppler umbilical artery flow velocimetry. On
      the contrary, inhibin B levels were significantly higher in samples from
      umbilical cord vein than artery, in both groups of pregnant women (both p <
      0.001). However, women with abnormal Doppler umbilical artery flow velocimetry
      had inhibin B levels significantly higher than healthy controls (p = 0.005) only
      in the umbilical cord artery, but not in the vein. In the presence of abnormal
      Doppler umbilical artery flow velocity, the concentrations of inhibin B are
      increased in the arterial umbilical circulation, suggesting that inhibin B is
      released from multiple fetal sources as a response to hypoxemic stress. As
      inhibins may affect the hypothalamus-pituitary-adrenal axis which plays an
      important role in the mechanisms of adaptations to the post-natal life, inhibin B
      in fetal circulation might then be beneficial to a fetus whose intrauterine
      survival is threatened by impaired umbilical-placental blood flow.

PMID- 14593238
TI  - Vascular endothelial growth factor and angiogenin levels during fetal development
      and in maternal diabetes.
AB  - We evaluated the concentrations of vascular endothelial growth factor (VEGF) and
      angiogenin in the umbilical cord blood from 14 fetuses with erythroblastosis or
      alloimmune thrombocytopenia and at birth from 28 preterm fetuses, from 42 healthy
      term fetuses, and from 24 term fetuses born to mothers with insulin-treated
      diabetes. A correlation appeared between VEGF and angiogenin levels (r = 0.44, p
      = 0.038). The gestational age correlated with both VEGF (r = 0.38, p = 0.0008)
      and angiogenin levels (r = 0.80, p = 0.0001). The concentration of VEGF was lower
      in fetuses born to mothers with insulin-treated diabetes than in the healthy term
      fetuses (p = 0.0028), but this difference was absent for angiogenin (p > 0.05).
      In conclusion, in umbilical cord plasma, a developmental increase was evident in
      concentrations of VEGF and angiogenin during the last trimester of gestation.
      That the umbilical cord VEGF level was lower in term fetuses born to mothers with
      diabetes than in term fetuses of healthy mothers may be associated with an
      aberrant fetal vascular development in diabetic pregnancies.

PMID- 14593239
TI  - Use of sound-absorbing panel to reduce noisy incubator reverberating effects.
AB  - OBJECTIVES: To assess the amplification and distortion of noise in incubators by
      measuring noise levels from various sources under various conditions. STUDY
      DESIGN: We recorded sound pressure levels (SPL) of background noise, baby crying,
      alarms and porthole closing with the incubator hood open or closed. Then we tried
      to reduce the sound level in the incubator by applying a sound absorbing panel to
      the ceiling of the hood. RESULTS: The sound sources analysed produced very high
      SPL. In free field baby crying and porthole noise were, respectively, 81-83 dB
      and 70-71 dB, closing the hood they raised to 84-87 and 73-74 dB: this means that
      the noise perceived by a baby in the incubator had twice the SPL of the same
      noise emitted in a free field; alarm noise was 56-57 dB inside incubators. Sound
      emitted inside the hood was also distorted, i.e. it had different features from
      the same source in a free field. The insulating panel prevented amplification and
      distortion due to the hood and reduced the SPL of alarms. Only background noise
      did not decrease with the panel. Sound absorbing panel reduced baby's crying,
      porthole noise and alarm noise SPL to 82-85, 70-71 and 50-51 dB, respectively.
      CONCLUSIONS: Incubators are reverberating environments, which amplify the baby's
      cry and other noises produced inside the hood. The frequency components of noises
      are altered by the hood. The sound absorbing panel reduced this phenomenon.

PMID- 14593240
TI  - Age-related changes in intracellular TH1/TH2 cytokine production,
      immunoproliferative T lymphocyte response and natural killer cell activity in
      newborns, children and adults.
AB  - To evaluate the development of the neonatal immune system, we measured T
      lymphocyte response to Con A, intracellular IL-2, IL-4, IFN-gamma and IL-10
      production, and natural killer cell (NKC) activity in 12 very preterm, 12 preterm
      and 20 term neonates, 10 children and 10 adults. Immunoproliferation to Con A was
      significantly lower in cord blood than in children or adults. The percentage of
      CD4+ lymphocytes was significantly higher in newborns while CD8+ cells were
      higher at older ages, with a resulting gradual decline of the CD4+/CD8+ ratio.
      The percentage of IL-2-producing CD4+ and CD8+ cells was higher in all newborn
      groups than in children and adults, while the percentage of IL-4-producing cells
      was higher for CD8+ and lower for CD4+ cells in cord blood than in children and
      adults. Neonates had substantially lower percentages of CD4+ and CD8+ IFN-gamma
      producing cells. A significant negative correlation was observed between
      gestational age and IFN-gamma-CD4+-, IL-2-CD8+-, and IL-10- CD4+-producing cells.
      In addition, a positive correlation was found between gestational age and IL-10
      CD8+-producing cells. Percentages of CD4+/CD45RA+ cells were higher and
      CD4+/CD45RO+ percentages were lower in newborns than in children and adults. NKC
      activity in infants was significantly correlated with gestational age and
      significantly impaired compared to children and adults. On the whole, these
      results suggest a gradual development of immunity during gestation and show
      significant immaturity of cellular immune response at birth. The reduction of NKC
      activity, the lower proliferative response of T cells, the reduced cytotoxic
      response and a dysregulated cytokine production may contribute to the neonatal
      increased risk of infection and to the low incidence of graft-versus-host disease
      after cord blood transplantation.

PMID- 14593241
TI  - Comparison of fecal flora following administration of two antibiotic protocols
      for suspected maternofetal infection.
AB  - Two protocols are used by French neonatologists for the treatment of suspected
      maternofetal infection (SMFI). Three groups of premature and term neonates were
      included to study the impact of antibiotics on fecal flora: 10 infants with SMFI
      treated with amoxicillin and netilmicin (group BI), 10 infants with SMFI treated
      with amoxicillin, cefotoxime and netilmicin (group TRI) and 10 infants without
      antibiotic therapy as controls (group C). Group BI samples were colonized with
      Klebsiella oxytoca and Escherichia coli resistant to amoxicillin and by
      Eneterococcus faecium and coagulase-negative staphylococci. In group TRI
      biodiversity of the intestinal flora was low, with rapid growth of staphyloccoci
      and occurrence of Candida spp. These modifications of the intestinal flora should
      encourage us to use antibiotic treatment as targeted as possible.

PMID- 14593242
TI  - The influence of piglet birth weight on physical and behavioural development in
      early life.
AB  - The objective of this study was to determine whether body weight at birth
      influences the physical and behavioural development of the neonatal pig. Sixteen
      sows and their litters were randomly allocated into four treatment groups. From
      the normal distribution curve of their birth weight, piglets were sub-divided
      into three groups: (1) low (<10th percentile) (2) normal (10-90th percentile) and
      (3) high (>90th percentile). To assess behavioural development, each litter was
      exposed to a ball placed in the creep area for a period of 1,800 s, and evaluated
      once over a 3-day period starting on either 5, 7, 14 or 21 days of postnatal
      life. Their response to, and interaction with, an object was used to calculate a
      numerical index of piglet behavioural development. Teat order was calculated
      following observations during consecutive suckling on days 11, 13 and 15 of life,
      and dominance hierarchy was assessed on day 12, 14 and 16. Individual body weight
      was recorded on days 0, 5, 7, 14 and 21 of postnatal life. Statistical
      differences between groups were analysed using general linear model, analysis of
      variance. Regression analyses were used to determine relationships between
      physical and behavioural development with teat order and dominance. There was a
      significant (p < 0.001) relationship between birth weight, growth performance and
      behavioural development. Behavioural developmental index (BDI) significantly
      improved (p < 0.001) with age and was also influenced by the day on which the
      ball was introduced (p < 0.01). Body weight on day 1 of the test was
      significantly (p < 0.001) correlated to BDI and age at test. Piglets
      demonstrating compensatory growth were more dominant and exhibited an improved
      behavioural developmental score than their slower growing littermates. In
      conclusion, compromised growth in utero can have a detrimental effect on the
      physical and behavioural development of the neonate. Animals with an enhanced
      developmental index in conjunction with a higher dominance value exhibited a
      improved neonatal growth performance.

PMID- 14593243
TI  - LPS-induced changes in myocardial markers in neonatal rats.
AB  - Lipopolysaccharide (LPS) produces varied systemic metabolic effects. We studied
      the effects of LPS on the cardiac fatty acid profile and its relationship to
      energy metabolism and inflammatory mediators that included TNF-alpha and nitric
      oxide synthase (NOS) in 10-day-old neonatal rat pups. Rat pups received an i.p.
      injection of LPS after a 4-hour starvation period, followed by collection of
      blood and cardiac tissue 4 h following LPS administration. Compared to controls,
      LPS induced significant hypoglycemia and hyperlactacidemia, suggesting the
      development of endotoxic shock. The result was a significant depression in total
      fatty acid levels as well as non-esterified fatty acid in the cardiac tissue of
      the LPS-treated pups. In addition, LPS-treated pups also showed a significant
      increase in TNF-alpha, NOS levels with a depressed redox state and energy
      metabolism in cardiac tissue. These observations suggest that endotoxic shock in
      10-day-old rat pups induces a systemic inflammatory response with a depression in
      fatty acid metabolism that may contribute to myocardial failure.

PMID- 14593244
TI  - Erythropoietin protects against necrotizing enterocolitis of newborn rats by the
      inhibiting nitric oxide formation.
AB  - BACKGROUND: Necrotizing enterocolitis (NEC) is an important neonatal disease with
      a high mortality rate; erythropoietin (Epo) is a hematopoietic growth factor.
      Functional Epo receptors are in the fetal and postnatal small bowel and their
      ligands are available for binding. Excessive nitric oxide (NO) production by an
      isoform of NO synthase inducible by inflammatory stimuli leads to changes in
      vascular permeability and tissue injury. The aim of this study was to investigate
      NO formation in an experimental model of NEC and the possible role of NO in the
      protection Epo provides against NEC. METHODS: Twenty-four Wistar albino rat pups
      were divided into three groups: group 1 = control; group 2 = hypoxia
      reoxygenation and saline; group 3 = hypoxia-reoxygenation and recombinant human
      EPO (rhEpo) pretreatment. rhEpo was given 750 U/kg/week by intraperitoneal
      injection 3 times a week for 2 weeks. On the 15th day, hypoxia was induced by
      placing the pups in a 100% CO(2) chamber for 5 min. After the hypoxia period the
      pups were reoxygenated for 10 min with 100% O(2) and returned to their mothers.
      All pups were killed 4 h after the hypoxia-reoxygenation period was over. The
      abdomen was opened and representative samples of injured areas were taken for
      histopathologic examination. Then nitrite levels were determined in the intestine
      by Griess Reagent. RESULTS: On histopathological examination, injury scores in
      group-2 animals were found to be significantly higher than in group-3 animals (p
      = 0.001). Significantly increased intestinal nitrite levels were found in group-2
      rats compared to the rats of groups 1 and 3 (p = 0.001 and p = 0.001,
      respectively). There was a positive correlation between the histological findings
      and the intestinal nitrite levels in group-2 and -3 animals (r = 0.94, p = 0.001;
      r = 0.99, p = 0.001, respectively). CONCLUSION: The present study demonstrates
      that the Epo-pretreated group had decreased levels of NO and limited mucosal
      necrosis in intestinal tissue samples. We believe that these results deserve
      further experimental studies in order to elucidate the possible effector
      mechanisms involved in the inhibitory relationship between Epo, NO and NEC.

PMID- 14593245
TI  - Comparison of pulmonary and inflammatory effects of lipid- and water-soluble
      components in meconium in newborn piglets.
AB  - To understand the pathogenesis of meconium aspiration syndrome, we compared the
      pulmonary and inflammatory effects of the water and lipid extracts of human
      meconium instilled into the lungs of newborn piglets. The piglets were
      artificially ventilated, made hypoxemic, and randomized into three groups. At
      start of reoxygenation, 3 ml/kg of one of the following mixtures was instilled
      intratracheally: (1) meconium (n = 12); (2) water extract of meconium (n = 12),
      and (3) lipid extract of meconium (n = 12). During 8 h of reoxygenation,
      hemodynamics, pulmonary gas exchange, lung mechanics, and interleukin-8
      concentrations in tracheobronchial aspirates were monitored. Oxygenation index (p
      = 0.04) and mean airway pressure (p = 0.04) increased more in the lipid extract
      group than in the water extract group. Dynamic compliance and mean arterial blood
      pressure decreased (p < 0.05) in the meconium and lipid extract groups, but not
      in the water extract group. At 8 h of reoxygenation, the interleukin-8
      concentration in the tracheobronchial aspirates was three times higher in the
      lipid extract group as compared with the water extract group (110 +/- 102 vs. 37
      +/- 27 pg/ml; p = 0.02). In conclusion, pulmonary dysfunction in meconium
      aspiration syndrome is caused by both the water- and lipid-soluble fractions of
      meconium, with stronger inflammatory and more detrimental effects promoted by the
      lipid extract than the water extract.

PMID- 14593246
TI  - Problems associated with collecting breath condensate for the measurement of
      exhaled hydrogen peroxide from neonates on respiratory support.
AB  - We developed a bedside method for collecting exhaled breath condensate (EBC) from
      neonates who were ventilated or receiving nasal continuous positive airway
      pressure (CPAP) and analyzed their EBC for hydrogen peroxide levels. A sufficient
      volume for analysis could be collected over 25-40 min from neonates on the
      ventilator and nasal CPAP (medians 5.3 and 2.7 ml, respectively). There was no
      significant difference between hydrogen peroxide levels from neonates on a
      ventilator or CPAP (median 0.28 vs. 0.38 microM, p = 0.06) and these were no
      different from a background with the ventilator or CPAP system alone (median for
      each 0.31 microM). The dilution of breath condensate by humidified gases plus the
      existence of background hydrogen peroxide resulted in this collecting setup being
      insufficiently sensitive to use for the detection of exhaled hydrogen peroxide in
      infants who were ventilated or on nasal CPAP.

PMID- 14593247
TI  - Chased PCR: A modified inverse PCR technique to characterize flanking regions of
      AT-rich DNA fragments.
AB  - The chased polymerase chain reaction (PCR) technique described here is a
      convenient method enabling the characterization of flanking regions of a known
      A/T-rich DNA fragment in two different successive steps. The first step includes
      a modified inverse PCR with inverted tail-to-tail primers, each with 35
      overhanging nucleotides for the insertion into a carrier plasmid. The second step
      consists of a technique similar to a site-directed mutagenesis. The chased PCR
      technique is simple, quick, versatile and efficient; it improves the inverse PCR
      technique and may be applied to any ligation-linker method. Consequently, the
      techniques for PCR-based gene isolation are more suitable for the isolation of
      missing sequences of A/T-rich or complex DNA.

PMID- 14593248
TI  - Analysis of the elements of catabolite repression in Clostridium acetobutylicum
      ATCC 824.
AB  - The PTSH gene, encoding the phosphotransferase protein HPr, from Clostridium
      acetobutylicum ATCC 824 was identified from the genome sequence, cloned and shown
      to complement a PTSH mutant of Escherichia coli. The deduced protein sequence
      shares significant homology with HPr proteins from other low-GC gram-positive
      bacteria, although the highly conserved sequence surrounding the Ser-46
      phosphorylation site is not well preserved in the clostridial protein.
      Nevertheless, the HPr was phosphorylated in an ATP-dependent manner in cell-free
      extracts of C. Acetobutylicum. Furthermore, purified His-tagged HPr from Bacillus
      Subtilis was also a substrate for the clostridial HPr kinase/phosphorylase. This
      phosphorylation reaction is a key step in the mechanism of carbon catabolite
      repression proposed to operate in B. Subtilis and other low-GC gram-positive
      bacteria. Putative genes encoding the HPr kinase/phosphorylase and the other
      element of this model, namely the catabolite control protein CcpA, were
      identified from the C. Acetobutylicum genome sequence, suggesting that a similar
      mechanism of carbon catabolite repression may operate in this industrially
      important organism.

PMID- 14593249
TI  - MRAD: Metabolic reaction analysis database--an entity-relationship approach.
AB  - The Metabolic Reaction Analysis Database (MRAD) is a relational database based on
      the Entity-Relationship (ER) model which combines information about organisms,
      biochemical pathways, reactions, enzymes, substrates, products and genes. It
      describes 244,596 genes in 79 organisms, 6,552 enzymes, and 3,552 reactions,
      3,100 substrates, 2,866 products and 118 metabolic pathways. The MRAD graphical
      user interface allows for the identification of metabolic reactions which are
      similar and dissimilar in multiple organisms, reactions in a pathway which are
      missing in an organism and using any combination between one to six of the
      biological entities of organisms, genes, pathways, enzymes, substrates and
      products to determine metabolic reactions. MRAD provides a powerful and efficient
      tool for the construction of flux balance models for metabolic engineering
      applications.

PMID- 14593250
TI  - Novel transporters from hemiascomycete yeasts.
AB  - We screened nearly one thousand random sequenced targets obtained by partial
      sequencing of 13 hemiascomycete genomes identified by higher amino acid sequence
      similarity to a non-Saccharomyces cerevisiae protein than to a S. Cerevisiae
      protein. Among those sequences we have identified 36 novel phylogenetic clusters
      of putative transporters which, according to the Transport Commission system (TC
      DB, 2002; http:// tcdb.ucsd.edu/tcdb), do not belong to acknowledged S.
      Cerevisiae protein families [De Hertogh et al.: Funct. Integr. Genomics
      2002;2:154-170; http://cbi.labri.u-bordeaux.fr/Genolevures]. These novel
      hemiascomycete transporters comprise 3 channels, 23 secondary transporters, 5
      primary transporters and 5 membrane proteins of unknown function.

PMID- 14593251
TI  - New antibiotic resistance cassettes suitable for genetic studies in Borrelia
      burgdorferi.
AB  - In this report we describe two distinct approaches to develop new antibiotic
      resistance cassettes that allow for efficient selection of Borrelia burgdorferi
      transformants. The first approach utilizes fusions of borrelial flagellar
      promoters to antibiotic resistance markers from other bacteria. The AACC1 gene,
      which encodes a gentamicin acetyltransferase, conferred a high level of
      gentamicin resistance in B. Burfdorferi when expressed from these promoters. No
      cross-resistance occurred between this cassette and the kanamycin resistance
      cassette, which was previously developed in an analogous fashion. A second and
      different approach was taken to develop an efficient selectable marker that
      confers resistance to the antibiotic coumermycin A1. A synthetic gene was
      designed from the GYRB301 allele of the coumermycin-resistant B. Burgdorferi
      strain B31-NGR by altering the coding sequence at the wobble position. The
      resulting gene, GYRB(SYN), encodes a protein identical to the product of GYRB301,
      but the genes share only 66% nucleotide identity. The nucleotide sequence of
      GYRB(SYN)is sufficiently divergent from the endogenous B. Burgdorferi GYRB gene
      to prevent recombination between them. The cassettes described in this paper
      improve our repertoire of genetic tools in B. Burgdorferi. These studies also
      provide insight into parameters governing recombination and gene expression in B.
      Burgdorferi.

PMID- 14593252
TI  - Dual control by regulators, GntH and GntR, of the GntII genes for gluconate
      metabolism in Escherichia coli.
AB  - Escherichia coli possesses two systems, GntI and GntII, for gluconate uptake and
      catabolism, whose genes are regulated by GntR as a repressor and GntH as an
      activator, respectively. Additionally, GntH exerts negative control of the GntI
      genes via the same binding element as that of GntR. We thus examined whether GntR
      involves regulation of the GntII genes or not. This regulation and the control by
      GntH were examined by using single-copy LACZ operon fusions and by RT-PCR,
      suggesting positive and negative regulation by GntR and positive regulation by
      GntH. Moreover, the introduction of mutations into possible GntR-binding elements
      revealed that both regulators share at least one of the elements. The results
      presented allow us to speculate that GntR initiates expression of the GntII
      genes, followed by their large induction by GntH when cells were grown in
      gluconate minimum medium. As in the case of the GntI genes, such a cross
      regulation between the GntI and GntII via the two regulators may be important for
      cells to grow with gluconate.

PMID- 14593253
TI  - Mutations in the N-terminus of the major coat protein (pVIII, gp8) of filamentous
      bacteriophage affect infectivity.
AB  - Filamentous bacteriophages are nonlytic, male-specific bacteriophages which
      infect Escherichia coli carrying an F-episome. The molecular mechanism of
      infection remains elusive, including the role of the major coat protein pVIII. In
      order to evaluate the contributions of major coat protein pVIII in the process of
      infection, two phage display libraries were generated. One library consisted of
      random amino acids at positions 2, 4, 5, 8, 11 and 12 of the N-terminus of major
      coat protein pVIII. The second library was generated by randomizing these
      positions as well as position 1. All these residues were previously shown to be
      exposed at the surface of the virions by being accessible to ligands. The
      infectivity of randomly selected mutant phages was analyzed. The present results
      demonstrate that phages modified at these positions can be correctly assembled
      and secreted into the exoplasm, although the efficiency was slightly lower than
      that of wild-type phage. Their infectivity varied greatly, and a general
      structural pattern underlying infectivity did not emerge. However, residual
      differences were observed between infectious and defective phage; in general,
      uncharged polar amino acids present at positions 5 and 11 of the N-terminus of
      pVIII reduced phage infectivity, whereas polar residues at position 8 facilitated
      infection. The first position of pVIII is remarkably critical for infection; when
      this alanine was substituted with other residues, most of the phages lost their
      infectivity. These results shed new light on the true complexity of random
      peptide pVIII phage display libraries.

PMID- 14593256
TI  - More needs to be done about assessing and managing pain.

PMID- 14593257
TI  - Clinical governance: trusts failing to meet the challenge.

PMID- 14593258
TI  - Matron who restrained a patient with bandages in a wheelchair.

PMID- 14593259
TI  - Patients' and nurses' perceptions of quality nursing activities.
AB  - Nurses and patients come from varying backgrounds and have different life
      experiences. Their perceptions regarding what comprises quality nursing care may
      differ. The objective of this article was to determine whether there is a
      difference in the perceived importance of nursing activities from the point of
      view of patients and nurses. If differing perceptions were found, the goal would
      then be to increase nursing awareness of these differences. A convenience sample
      of 30 nurses and 30 patients on a medical-surgical unit were surveyed about
      nursing care using a 41-item questionnaire. Data obtained were divided into four
      classes of nursing activities: psychosocial, physical, safety, and indirect.
      There was a significant difference in the perceived importance of nursing
      activities by nurses and patients in the psychosocial and safety categories.
      Nursing activities that may not be recognized as such by patients, or which are
      not seen as important to quality care, should be clarified for patients.
      Clarification may also be useful in helping patients to understand the
      professional nursing role. In addition, this insight may heighten patient
      satisfaction with caregiving.

PMID- 14593260
TI  - Nursing role in the management of constipation: use of laxatives.
AB  - Constipation is extremely common and may affect a variety of patients from
      different age groups. This article outlines the causes of constipation and
      describes the nurse's role in the management of patients with constipation, from
      assessment to intervention. The skills required of the nurse, including taking a
      detailed history from the patient, the subsequent examination, and the
      administration of laxatives are discussed in detail. Nurses are best placed to
      assess, plan, implement and evaluate care for patients presenting with
      constipation. The article stresses the need for healthcare professionals to aim
      to prevent constipation and to identify early those patients at risk of
      developing constipation, to ensure that patients' needs are met fully.
      Recommendations for good practice are given.

PMID- 14593261
TI  - A history of insulin: from discovery to modern alternatives.
AB  - Following on from the first article in this series (Vol 12(18): 1091-5), which
      described the history of diabetes, this article, the second of three literature
      reviews, explores the early production and development of insulin, from its
      initial production in a university laboratory to becoming a major pharmaceutical
      product. Also discussed are the various forms of insulin developed over the last
      80 years and their means of delivery to the patient. The future is considered and
      the development of insulin analogues (substances that mimic the effect of human
      insulin) is described. The article also looks at the introduction of DAFNE (dose
      adjustment for normal eating) - an intensive programme of education aimed at
      teaching individuals the necessary skills to adjust their own insulin injection
      dosage to reflect their individual eating patterns.

PMID- 14593262
TI  - Critical thinking at the bedside: a practical perspective.
AB  - This article provides a comprehensive review of critical thinking from both a
      theoretical and, more importantly, a practical perspective. The theoretical
      detail with regard to critical thinking is extensive. The many models developed
      from the literature are often too complex and difficult to interpret in relation
      to clinical practice situations. If theory cannot be integrated into practice
      then its value to nursing should be questioned. The task now is to formalize and
      cement the connections between the two concepts at the bedside.

PMID- 14593263
TI  - Giving medicinal information to mentally capacitated patients.
AB  - Roy was advised that a new drug which had just come on the market would assist
      his chronic depression. He was not given any further information, but after
      taking it for a few days found that it had a strong effect on his personality and
      he became aggressive and violent. As a consequence of a fight at work he lost his
      job and now claims that had he known of these effects he would not have taken the
      new drug.

PMID- 14593264
TI  - ProfiCare: an alternating pressure-relieving mattress.
AB  - Risk assessment tools should only act as a guide to patient status rather than
      definitive diagnosis. Emphasis must be placed on not using the Waterlow score in
      isolation but in conjunction with clinical judgement. We must therefore attempt
      to minimize opportunities for disagreement over pressure ulcer risk scores
      through the selection of appropriate support surfaces based on a thorough
      consideration of costs of pressure ulcers for the patients, institutions and
      healthcare professionals. This product focus advocates that ProfiCare replacement
      mattresses are an option as they are designed for use on a hospital bed frame and
      provide alternating and static patient support surfaces.

PMID- 14593265
TI  - Students must develop a professional identity.

PMID- 14593266
TI  - Tissue viability research must be encouraged.

PMID- 14593267
TI  - Managing patients unable to tolerate therapeutic compression.
AB  - Managing patients with venous ulceration who are unable to tolerate therapeutic
      compression bandaging is a challenging clinical problem. This study followed a
      group of 28 such patients who were treated with three layers of graduated
      Tubigrip as an alternative to therapeutic compression. It also investigated
      factors that influenced nurses in deciding to use this bandaging system. Patients
      were followed until their ulcers healed or for a maximum of 12 weeks. The
      decision to use three layers of graduated Tubigrip was based on 19 patients'
      desire to wear their normal shoes (67.9%) and the convenience of access to the
      ulcer by eight patients (28.6%) (to permit frequent dressing changes for large or
      infected ulcers, and for the daily application of steroidal creams to periulcer
      skin). Fourteen patients' ulcers had healed within the 12-week study period. The
      remaining 14 patients had a mean reduction in ulcer area of 4.6 cm(2) (SD = 7.4),
      and median of 2.3 cm(2) (range 28.5). The authors found three layers of graduated
      Tubigrip useful for managing patients who cannot tolerate therapeutic forms of
      compression.

PMID- 14593268
TI  - Low-frequency ultrasound to manage chronic venous leg ulcers.
AB  - Chronic leg ulceration costs the NHS around pound 500 million per year (Moffatt
      and Dorman, 1995) so it is not surprising that the condition attracts attention
      from manufacturers of medical devices. However, the evidence available for many
      novel technologies is scant and a systematic approach to product evaluation is
      essential to avoid the adoption of ineffective and therefore costly measures. A
      low-frequency ultrasound device was presented in clinic as an aid to stimulate
      and accelerate healing in otherwise recalcitrant wounds. There followed a
      systematic evaluation of the product including a literature review of the mode of
      action, safety and efficacy, followed finally by a product evaluation with case
      studies used as outcome measures. In this case, the product proved to be a useful
      tool in the management of chronic wounds, not only for healing but also for pain,
      pigmentation and odour reduction. The importance of understanding fully a novel
      technology and how it fits with clinical practice cannot be underestimated.

PMID- 14593269
TI  - Improving pressure ulcer care through designer education.
AB  - In 2001, a tissue viability audit was undertaken within a medical directorate of
      an acute district general hospital. The audit highlighted deficiencies in the
      knowledge base of the staff and in the care given to prevent and manage pressure
      ulceration. As a result, the tissue viability nurse, head of nursing (medical
      directorate) and lecturer in tissue viability identified educational and service
      needs and developed a specifically designed education programme that integrated
      diploma- and degree-level study. Pre- and post-course questionnaires were
      designed to assess students' theoretical knowledge; this was combined with an
      assessment that focused on the implementation of the pressure ulcer prevention
      and management guidelines. The success of the programme was demonstrated by an
      increase in nurses' knowledge of pressure ulcer prevention and management. This
      positive outcome could not have been achieved without the willingness of the
      trust manager, tissue viability nurse and nurse educator to work together and
      support the development of this new initiative.

PMID- 14593270
TI  - Balancing cost-effectiveness with quality in tissue viability.
AB  - The 21st century has seen an increase in the importance placed on the skills of
      healthcare practitioners. They now need to be able to demonstrate cost
      effectiveness and balance it with quality in the delivery of care in the NHS.
      This emphasis is driven largely by the emergence of initiatives such as evidence
      based practice, clinical governance and cost-effectiveness evaluations. The
      pressure to demonstrate cost-effective quality practices is becoming more and
      more prominent in the NHS. This article will discuss the practicalities and
      implications these pressures have on tissue viability and wound care providers.

PMID- 14593271
TI  - An overview of Acticoat dressing in wound management.
AB  - This article reviews the in vitro and in vivo studies available on a new
      nanocrystalline silver dressing, Acticoat (Smith & Nephew), and discusses their
      relevance to the availability of this product on the Drug Tariff. The addition of
      nanocrystalline silver dressings will make a valuable contribution to wound care
      in the community, in terms of providing continuity of care for patients who are
      discharged from hospital and also in preventing admission to hospital with non
      manageable wound infection.

PMID- 14593272
TI  - Have you heard the one about.

PMID- 14593274
TI  - The experience of uncertainty for individuals with HIV/AIDS and the palliative
      care paradigm.
AB  - This small qualitative study investigated the lived experience of individuals
      with HIV/AIDS, exploring the uncertainty related to episodes of life-threatening
      illness followed by recovery, 'revival'. The themes that emerged related to the
      unpredictability of when death would occur. The participants described the
      dilemma of living with a chronic illness with a totally unpredictable disease
      trajectory. Following periods of being extremely unwell, individuals would then
      recover and experience periods of relative well-being, only to succumb to another
      infection later. The findings highlighted the uncertainty that pervades all
      aspects of HIV-positive individuals' lives as they face death. An awareness of
      this may be important in those offering palliative care to those with HIV/AIDS.

PMID- 14593273
TI  - Nurses' perceptions of the Liverpool Care Pathway for the dying patient in the
      acute hospital setting.
AB  - The Liverpool Care Pathway for the dying patient (LCP) was developed to transfer
      the hospice model of care into other care settings. It is a multiprofessional
      document that provides an evidence-based framework for the dying phase. It
      provides guidance on the different aspects of care required including comfort
      measures, anticipatory prescribing of medication, and discontinuation of
      inappropriate interventions. Additionally, psychological and spiritual care and
      family support is included. This article presents the findings of a study to
      explore hospital nurses' perceptions of the impact of the LCP using focus group
      interviews. Data were analysed for emerging themes using thematic analysis. The
      results suggest that the nurses have generally found that the LCP had a positive
      impact on patients, their families and also on nurses and doctors. This article
      will explore these benefits, as well as potential barriers to its use.

PMID- 14593275
TI  - The palliative care needs of ethnic minority patients attending a day-care
      centre: a qualitative study.
AB  - The aim of this study was to assess the culture-specific palliative care needs of
      ethnic minority patients. Qualitative semi-structured interviews were conducted
      using elements of phenomenology with four ethnic minority patients who were
      attending a day-care centre. Although the aim was to assess cultural needs, it
      was found that the patients expressed basic human needs rather than culture
      specific ones. The theme of acculturation, where patients 'fit in' with the
      dominant culture, was predominant. This suggests that stereotypical cultural care
      may not always be appropriate, as micro-cultures and individual diversity within
      cultures exist. These should be explored in the cultural assessment of ethnic
      minority patients.

PMID- 14593276
TI  - Pilot of a workbook for children visiting a loved one in a hospice.
AB  - A palliative care counsellor developed a workbook for use by children aged 5 to
      14 years visiting a loved one in a hospice. This article reports the findings of
      a small qualitative pilot study exploring how children used the workbook, their
      views on it and the views of their families and hospice staff. The seven children
      in the study all enjoyed having the workbook. It provided opportunities for them
      to interact and build relationships with the staff and to become more involved in
      their visits to the hospice. Nurses and staff thought the workbook had the
      potential to help nurses and parents respond to questions or to stimulate
      discussion. Children used the workbook in different ways, highlighting the need
      for a flexible approach. It is essential when using such a tool that individual
      and family needs are respected. The study also raised issues regarding the need
      for training and emotional support for staff.

PMID- 14593277
TI  - Should two senior cancer-nursing posts be integrated as one leadership function?
AB  - Uncertainty exists regarding the roles of the nurse consultant in cancer and
      palliative care and the lead cancer nurse. This article argues that there are
      advantages in combining the two posts. The discussion draws on relevant
      literature and argues that both posts have the same outcomes, which are achieved
      through different means and approaches to the delivery of cancer services. In
      order to make the combined post work within a trust, a particular support and
      structure is required. There may be a greater potential for cancer nursing
      because the leadership role combines the strategic perspective of the lead cancer
      nurse with the nurse consultant's focus on practice development and the
      professional development of staff.

PMID- 14593278
TI  - Is it ever too late for holistic cancer care?

PMID- 14593279
TI  - Economic evaluation of specialist cancer and palliative nursing: a literature
      review.
AB  - Little progress has been made in economic evaluation of specialist cancer and
      palliative care nursing. A literature review of economic studies of clinical
      nurse specialists (CNSs) was undertaken to assess how the measurement of economic
      outcomes has been tackled in the literature to date. The initial search found 400
      studies. Abstracts from all the studies were reviewed but only 17 studies met the
      basic criteria for inclusion, reporting primary cost and outcomes data, and
      clearly specifying the role of a CNS. All of the studies but one focused on
      direct patient care rather than other CNS roles and were undertaken alongside
      effectiveness studies. The economic evaluations considered only a narrow range of
      costs, but a wide range of outcomes. Specific nursing outcomes were only reported
      in a minority of studies. None of the studies reported cost-effectiveness ratios.
      However, CNS interventions were reported to be both less costly and more
      effective than alternative forms of care, negating the need for further cost
      effectiveness analysis. Overall, the papers were not of good quality, reducing
      the validity of the findings. Robust economic evaluations of the CNS role need to
      be undertaken. These should involve nursing researchers and practitioners so that
      evaluations reflect the complex and multidimensional nature of CNS care and meet
      the required standard of evidence to influence practice.

PMID- 14593280
TI  - Economic evaluation of specialist cancer and palliative nursing: Macmillan
      evaluation study findings.
AB  - Economic evaluation of specialist nursing interventions is challenging because of
      the complex nature of interventions and the difficulty of describing nursing
      outcomes in simple ways. This article discusses data from a study of Macmillan
      specialist cancer nursing. Resource-use data and nursing-outcome data were
      collated from 76 case studies of patients referred to 12 specialist cancer and
      palliative nursing teams (home-based and hospital-based) in the UK. Specific
      outcomes related to nursing were defined, and cost and nursing outcome data were
      analysed together. The data suggested that patients who reported better nursing
      outcomes had a higher proportion of specialist nursing interventions than those
      reporting poor nursing outcomes (45% versus 25%). Also, the overall pattern of
      health-care use was different for those patients who reported positive nursing
      outcomes. This suggests that positive nursing outcomes can influence patients'
      access to other health services. The data supported specific hypotheses regarding
      ways that specialist nurses can influence the cost-effectiveness of care. These
      data do not constitute a comparative evaluation study, as no control group was
      identified. Such results are nevertheless important as this type of data has not
      been gathered previously.

PMID- 14593282
TI  - Palliative care for Hindus.
AB  - This article presents the chronology and significance of events that typically
      occur before and after death in the Hindu household. In the first section the
      authors concentrate on issues and consideration before death that are potentially
      of relevance to healthcare professionals providing terminal care. The section
      that follows aims to help healthcare professionals to understand the events that
      often occur in the immediate aftermath of death. It is hoped that this will help
      healthcare professionals provide holistic care for their patients.

PMID- 14593281
TI  - The Preferred Place of Care document: an opportunity for communication.

PMID- 14593283
TI  - Reflections on pain management: a case study.
AB  - This article discusses issues relating to pain management at the end of life.
      Through reflections on a case study of a single patient many aspects of pain
      management are highlighted. These include difficulties in assessing pain, the
      need to respect patient autonomy, out-of-hours concerns and the possible role of
      integrated care pathways. The need to be aware of the potential value of non
      pharmaceutical approaches is also discussed.

PMID- 14593284
TI  - [Ten-year surveillance of nosocomial surgical site infections in an orthopedic
      surgery department].
AB  - PURPOSE OF THE STUDY: Surveillance of nosocomial surgical site infections was
      instituted in our department in June 1991. We report our first nine years
      experience. MATERIAL AND METHODS: This study concerned the first 9 years (June
      1991-June 2000) of a surveillance program designed to monitor nosocomial surgical
      site infections in our orthopedic surgery department. During this period 9,696
      patients underwent surgery, including 2745 for hip replacements and 1016 for knee
      replacements. The diagnosis of infection was based on the Centers of Disease
      Control criteria. Beginning in 1997, the program was widened to include all
      indications for prophylactic antibiotics, being limited before that time to
      indications for arthroplasty and spinal surgery. RESULTS: The overall rate of
      infection was 1.25%; 0.55% for hip arthroplasty and 1.77% for knee arthroplasty.
      The rate of infection among hip surgery patients over the last 5 years was much
      higher for prosthesis revision (2.37%) than for first-intention implantations
      (0.16%). The majority of the isolated strains were Gram-positive (84%) including
      Staphylococcus sp. found in 65% of the cases. Multiple-strains were found in 23%
      of the infections. The rate of infection improved very significantly over the
      last five years both for knee arthroplasty and spinal surgery. The rate remained
      unchanged for hip arthroplasty. DISCUSSION: This 10-year survey enabled us to
      analyze the difficulties encountered and pinpoint errors or insufficiencies in
      data recording. We were also able to identify measures to be taken concerning
      patient follow-up. The improvement in the rate of infection over time appears to
      be multifactorial, undoubtedly related to wider use of prophylactic antibiotics,
      progress in hygiene and sterilization methods with institution of a quality
      assurance program, and team awareness. CONCLUSION: Surveillance of nosocomial
      infections is a recommended practice. We have found that the information provided
      can be beneficial if the data is statistically sound, pointing out the need for
      progress in patient follow-up.

PMID- 14593285
TI  - [Static and dynamic modifications of the cervical spine after laminoplasty for
      cervical spondylotic myelopathy].
AB  - PURPOSE OF THE STUDY: Cervical laminoplasty has been widely used in Japan as the
      treatment of progressive cervical myelopathy. However, in 1993, Guigui reported
      that extensive cervical laminectomy was enough for the treatment of cervical
      myelopathy secondary to stenotic conditions. The purpose of this report was to
      compare the results of extensive laminectomy as reported by Guigui in 1998 with
      those of laminoplasty in our series using exactly the same criteria for anatomic
      analysis. MATERIAL AND METHODS: Thirty patients aged over 40 years who underwent
      a spinous process splitting laminoplasty using a threadwire saw from C3 to C7
      without fusion for cervical spondylotic myelopathy were reviewed retrospectively
      with an average follow-up of 3.7 years. Functional results were evaluated
      according to the Japanese Orthopedic Association scoring system for cervical
      myelopathy. Lateral views in the neutral position, in flexion, and in extension
      of the preoperative cervical roentgenograms were analyzed in comparison with the
      last follow-up films in order to identify the change in the curvature of the
      cervical alignment, in the range of neck motion, in the intervertebral angular
      mobility, and in the anteroposterior displacement of the vertebral bodies, and
      finally to identify the incidence of spinal instability. These data were compared
      with those of extensive laminectomy published by Guigui. RESULTS: Seven patients
      (23%) developed postoperative changes in cervical spine curvature. Only one
      patient had a new destabilized level postoperatively. No patient required new
      surgery. Compared with the results obtained after extensive cervical laminectomy,
      incidence of new destabilized level or aggravated level was statistically lower
      after laminoplasty than after laminectomy. CONCLUSION: Spinous process splitting
      laminoplasty causes an ossification between the remaining spinous process and an
      unexpected fusion of the lateral mass. These results may prevent postoperative
      segmental destabilization.

PMID- 14593286
TI  - [Physiological value of pelvic and spinal parameters of sagital balance: analysis
      of 250 healthy volunteers].
AB  - PURPOSE OF THE STUDY: Sagital balance of the spine is a fundamental element
      necessary for understanding spinal disease and instituting proper treatment. The
      aim of this prospective work was to establish the physiological values of pelvic
      and spinal parameters of sagital balance of the spine and to investigate their
      interactions. MATERIAL AND METHOD: Pelvic and spinal parameters were measured on
      the standing radiographs of 250 healthy volunteers. The following parameters were
      measured on lateral views including the head, the spine and the pelvis: lumbar
      lordosis, thoracic kyphosis, sagital tilt at T9, sacral inclination, pelvic
      incidence, pelvic version, intervertebral angulation, and the vertebral
      cuneiformization from T9 to S1. These measurements were taken after
      digitalization of the radiographs. Two types of analysis were performed: a
      descriptive univariate analysis to characterize the angular parameters and
      multivariate analysis (correlation, principal component analysis) to detail the
      relative variations of these parameters. RESULTS AND DISCUSSION: Mean values
      were: maximal lumbar lordosis 61 +/- 12.7 degrees, maximal thoracic kyphosis 41.4
      +/- 9.2 degrees, sacral inclination 44.2 +/- 8.5 degrees, pelvic version 13 +/- 6
      degrees, pelvic incidence 55 +/- 11.2 degrees, sagital tilt at T9 10.5 +/- 3.1
      degrees. There was a strong correlation between sacral inclination and pelvic
      incidence (r=0.86), pelvic version and pelvic incidence (r=0.66), lumbar lordosis
      pelvic incidence pelvic version and thoracic kyphosis (r=0.9) and finally between
      pelvic incidence and the following parameters: sagital tilt at T9, sacral
      inclination, pelvic version, lumbar lordosis, and thoracic kyphosis (r=0.98). The
      relations between the different parameters studied demonstrated that saggital
      tilt at T9, which reflects spinal balance, is determined by three independent
      factors. The first is a linear combination of pelvic incidence, lumbar lordosis,
      and sacral inclination. The second is pelvic version. The third is thoracic
      kyposis. CONCLUSION: This work provided a useful tool for analyzing and
      understanding anteroposterior imbalance in patients with spinal disease and also
      a means of calculating corrections to be made with treatment, established from
      the linear regression equations which were elaborated.

PMID- 14593287
TI  - [Proximal 4-part humerus fractures treated by antegrade nailing with self
      stabilizing screws: 31 cases].
AB  - PURPOSE OF THE STUDY: We present results of an internal fixation procedure for 4
      part fractures of the upper part of the humerus with or without impaction.
      MATERIAL AND METHODS: Antegrade nailing with self-stabilizing screws, by
      Telegraph nail, was used in 31 patients treated between June 1998 and June 1999.
      The standard insertion technique or the cup-and-ball method were used for nail
      insertion depending on the type of fracture (Neer and Duparc classification), the
      cup-and-ball method allowing fixation of more complex fractures. Clinical and
      radiological data were available for 23 patients at a mean follow-up of two
      years. Functional outcome was assessed with the Constant score. RESULTS: At last
      follow-up, the rough Constant score was 63 and the age- and sex-balanced Constant
      score was 85. Mean antepulsion was 130 degrees. Outcome was significantly better
      for Duparc type 2 cephalotuberosity fractures (scapula valga) where the weighted
      Constant score was 93. There were two cases of necrosis. DISCUSSION: Complex
      fractures of the upper part of the humerus are a major therapeutic challenge. To
      date, there is no agreement on the most appropriate osteosynthesis method and the
      results of shoulder prosthesis after trauma remain controversial. The Telegraph
      nail appears to be a simple and reproducible method of achieving reduction,
      stability, and early mobilization. Functional outcome has been favorable for type
      2 cephalotuberosity fractures and only two cases of necrosis were observed in
      this series in patients with type 3 and 4 cephalotuberosity fractures. These good
      results are related to the self-stabilizing effect of the locking screws which
      allow a stable fixation and revascularization of the bony fragments by creeping
      substitution. This new system is an attractive alternative to shoulder prostheses
      in trauma victims with complex displaced fractures without impaction. The
      surgical technique remains difficult. It would appear reasonable to expect
      remarkable and reproducible results for impacted fractures.

PMID- 14593288
TI  - [Arthroscopy-guided treatment of fractures of the distal radius: 16 wrists].
AB  - PURPOSE OF THE STUDY: We report our experience with arthroscopy-guided treatment
      of fractures of the distal radius. MATERIAL AND METHODS: Between November 2001
      and June 2002, 16 patients (10 men, 6 women, mean age 51 years, age range 24-75
      years) underwent arthroscopy-guided treatment of articular fractures of the
      distal radius. Patients were installed with the arm held in a horizontal position
      with a brace, the wrist under traction. The same procedure was used in all cases:
      introduction of the arthroscope, joint cleaning and shaving, search for lesions,
      arthroscopy-guided treatment. Kirschner 2-mm pins were used for fixation in all
      cases, combined with 1.2-mm pins in the event of ligament injury. RESULTS:
      Arthroscopic exploration revealed cartilage impaction in 25% of the wrists and
      ligament injuries in 30%. One fixation disassembled and was not remounted. There
      were two cases of reflex dystrophy. There were no arthroscopy-related
      complications. Bone healing was achieved in eight weeks in all cases. The mean
      DASH score was 22.5 at six months follow-up (range 3-10). DISCUSSION CONCLUSION:
      Arthroscopy-guided treatment of fractures of the distal radius was attempted for
      the first time in the early 90s. Per-operative arthroscopy enables a good view of
      the fracture and associated lesions (cartilage impaction, scapholunate,
      lunotriquetral ligament injury) and facilitates control of the reduction.
      Arthroscopy is technically simple and is the technique of choice due to the lack
      of morbidity. Several authors have reported their experience in more or less
      extensive series. Two notions should be emphasized. First, defective intra
      articular reduction greater than 1 mm may lead to osteoarthritis of the wrist in
      90% of the cases. Secondly, intra-operative imaging (fluoroscopy) does not
      provide sufficient precision to visualize a 1-mm stairstep in the articular
      surface, raising the risk of radiocarpal degeneration at mid term despite often
      satisfactory postoperative x-rays. We thus propose intra-operative arthroscopy to
      control the treatment of all articular wrist fractures, with or without
      displacement, in order to ensure satisfactory reduction with less than 1-mm
      defect in the articular surface and to search for and treat any associated bone
      or ligament injuries not diagnosed before surgery.

PMID- 14593289
TI  - [Reasons why musicians consult hand surgeons].
AB  - PURPOSE OF THE STUDY: Musicians occasionally consult orthopedic surgeons,
      particularly upper limb specialists. We wanted to learn more about the reasons
      why musicians attend orthopedic clinics. MATERIAL AND METHODS: We analyzed
      retrospectively 227 case files of musicians who consulted our center between 1994
      and 2001. We noted patient related factors (age, gender, musical experience,
      level of performance, daily practice schedule) and their reasons for consulting
      (pain, discomfort, advice). We studied the medical history of the patients and
      searched for predisposing or triggering elements. We also recorded therapeutic
      options proposed. RESULTS: Our series included 119 men (52%) and 108 women, mean
      age 35 years with 27 years of musical experience on the average. Instruments
      played were mainly the piano (41%), the violin (19%), and the guitar (15%).
      Patients playing wind instruments, who consult more often for ENT problems, were
      exceptional. On the average, the patients played their instrument 4 hours daily.
      One-third of the patients were high-level amateurs, one-third were professionals,
      and one-quarter were lower-level amateurs. There was a small proportion of
      soloists or professors. Two-thirds of the musicians presented disorders of the
      musculoskeletal system, particularly trauma sequelae. Signs of overuse were
      present in 18% of the patients, mainly women, signs of misuse due to
      inappropriate or defective technique in 8.8%, and dystonia in 5.7%. Psychological
      problems were noted in 4 patients. More than one half of the patients had
      obtained medical advice prior to consulting an orthopedic surgeon and the very
      large majority had been referred by specialized physical therapists. A surgical
      procedure was proposed for only 19% of the patients presenting an orthopedic
      disorder. DISCUSSION: This study presents a diversified panel of musicians
      consulting orthopedic surgery clinics. Practicing schedules varied in the study
      population from one to five hours daily. More than half the patients complained
      of pain but 18% consulted because they perceived a problem when playing and 17%
      consulted simply for advice. Our findings recall that musicians comprise a
      sensitive population requiring careful overall management. Unlike series
      published to date, we had a majority of men. Problems involving an orthopedic
      disorder or trauma and trauma sequelae predominated. In the literature, diagnosis
      has been oriented by the specialty of the consulting physician. We found that our
      patients who suffered from overuse had often recently changed their habitual
      practicing methods or conditions. The diagnosis of misuse was facilitated when
      the patient was examined with his/her instrument. The low rate of dystonic
      disorders was probably related to the fact that nearly half of our patients were
      followed regularly by a physical therapist. We did not observe any case of
      excessive laxity or Linburg Comstock syndrome which exceptionally have functional
      impact. The very large majority of our patients were referred by physical
      therapists and when surgery was necessary, the procedure was performed in
      accordance with accepted rules concerning the therapeutic management of
      musicians.

PMID- 14593290
TI  - [Treatment of bony fibrous dysplasia with calcium-phosphate cement: a case
      report].
AB  - We report successful use of calcium-phosphate cement for the treatment of benign
      polyostotic fibrous dysplasia in a patient who had undergone several unsuccessful
      surgical procedures. As no autologous bone was available for further grafting, we
      used a bone substitute to fill two defects, one in the upper part of the humerus
      and the other in the radial shaft. The curettage cavity was filled with calcium
      phosphate hydroxyapatite cement. The type of bone substitute was chosen for its
      specific properties: mineral structure similar to bone, microporosity, resistance
      to compression between cancellous and cortical bone, composition favorable to
      exchange between the crystals and the interstitial medium. Outcome was favorable
      early for the shoulder and later for the forearm after surgery for recurrence.
      Due to progress in the development of diphosphonates, indications for surgery for
      fibrous dysplasia have been reduced. There remains a risk of recurrence and
      incomplete results but bone substitute filling can be a useful alternative to
      autografts and complementary fixation. Calcium-phosphate cement is an easy-to-use
      paste-like product with interesting physicochemical and biological properties
      making it a leading choice for bone substitution.

PMID- 14593291
TI  - [Anterior radial nerve transposition in humerus midshaft fractures: anatomic and
      clinical study].
AB  - PURPOSE OF THE STUDY: Plate fixation of midshaft humerus fractures raises the
      risk of radial nerve injury. Anterior transposition of the radial nerve has been
      proposed as a possible solution but few reports have been published. The purpose
      of the present study was to validate the effect of transposition on the
      transposed radial nerve and its branches. MATERIAL AND METHODS: We conducted an
      anatomic study on 10 cadavers. The length of the radial nerve between 2 anatomic
      landmarks was determined before and after transposition and plate fixation. A
      clinical evaluation was performed four years after surgery in 6 patients with
      midshaft humerus fractures treated with plate fixation after radial nerve
      transposition. RESULTS: The anatomic study demonstrated a mean gain of 11 mm in
      the length of the radial nerve with no problem for the transposed nerve or its
      branches. Clinically, osteosynthesis was facilitated and tension on the nerve was
      reduced. DISCUSSION: These 2 complementary studies demonstrated the releasing
      effect of transposition on the radial nerve and the facilitated osteosynthesis
      reported by others. The benefit of transposition is particularly important when
      bone fixation is particularly difficult to achieve without risk of injuring the
      radial nerve. Transposition does however require an extensive dissection, and the
      patient must be informed. CONCLUSION: The ideal indication for anterior
      transposition of the radial nerve is an oblique fracture of the mid-third to
      lower-third of the humeral shaft with radial palsy at onset. A certain degree of
      comminution facilitates the technique. Indications for this technique could
      however be widened to include cases of difficult osteosynthesis where the option
      to transpose the radial nerve is always a peroperative decision.

PMID- 14593292
TI  - [Multifocal osteomyelitis as the first manifestation of chronic granulomatous
      disease].
AB  - Chronic granulomatous disease is a rare immune disease related to an anomaly in
      phagocytes NADPH oxidase. The characteristic clinical feature is early recurrent
      and sometimes serious infection. We report the case of a 22-month-old child who
      developed multifocal osteomyelitis, an unusual inaugural manifestation of chronic
      granulomatous disease. Septic chronic granulomatous disease is an uncommon
      differential diagnosis in children who develop recurrent infections. Diagnosis is
      established with specific blood tests: reduction of tetrazolium nitroblue,
      chemoluminescence test, molecular analysis. Therapeutic management must be
      undertaken as early as possible in order to preserve the long-term prognosis. No
      curative treatment is currently available. Aggressive treatment of each
      infectious focus with an adapted antibiotic regimen and in certain cases surgical
      debridement is required in addition to long-term antibiotic prophylaxis.

PMID- 14593293
TI  - [Spinal locations of pigmented villonodular synovitis: case report and review of
      the literature].
AB  - Pigmented villonodular synovitis is rarely observed in the spine: less than
      thirty cases have been reported. We report a new case observed in the cervical
      spine and review the pertinent literature. The clinical and radiological
      presentation of these forms of villonodular synovitis is non-specific and similar
      to that if primary or secondary spinal tumors. Histology is indispensable for
      certain diagnosis. Complete surgical resection is the treatment of choice but
      with a risk of recurrence to the order of 20%. Non-surgical treatments have not
      proven to be effective for spinal villonodular synovitis. Regular MRI
      surveillance is indicated. Spinal localizations may raise difficult technical
      problems in the event of recurrence.

PMID- 14593294
TI  - [Simultaneous dislocation of the interphalangeal joints of the index finger].
AB  - A crush injury caused simultaneous posterior dislocation of the interphalangeal
      joints of the index without associated fracture. Orthopedic treatment was used
      because a stable reduction was achieved without difficulty. The hand was
      immobilized for three weeks followed by rehabilitation exercises. Complete
      functional recovery was achieved with pain-free joints. We recommend starting the
      reduction at the distal interphalangeal level in order to allow relaxation of the
      deep flexor tendons favoring reduction of the proximal interphalangeal joints.

PMID- 14593295
TI  - [Comments on the Women's Health Initiative (WHI) and the Million Women Study
      (MWS) which question the usefulness of hormone substitution during menopause].

PMID- 14593296
TI  - [Quality of life instruments for women with pelvic organ prolapse].
AB  - OBJECTIVES: Our goal was to develop quality of life questionnaires in French for
      women with pelvic organ prolapse. MATERIAL AND METHOD: From two questionnaires
      previously developed for prolapse and validated in English, the Pelvic Floor
      Distress Inventory and the Pelvic Floor Impact Questionnaire, we have developed
      two questionnaires in French, the Inventaire des Symptomes de Prolapsus (ISP) and
      the Questionnaire sur l'Impact du Prolapsus (QIP). The ISP assesses symptom
      distress in women with pelvic floor disorders and measures how much these
      symptoms bother women. The QIP assesses life and emotional impact. These
      questionnaires were constructed after a double translation, a double expertise
      and patient interviews. A complete cross-validation into French is currently
      unfeasible due to cost considerations. RESULTS: The ISP and QIP questionnaires
      assess urinary, colorectal-anal and vaginal symptoms in relation to pelvic floor
      disorders. Both questionnaires significantly correlated with urinary and
      colorectal-anal symptoms. The main advantage of these instruments is the use of
      scales, with separate simple score for each scale. CONCLUSION: Based on two
      previously validated English questionnaires, the PFDI and the PFIQ, we have
      developed the first quality-of-life instruments in French for women with pelvic
      organ prolapse, the ISP and the QIP.

PMID- 14593297
TI  - [Promontofixation procedure: use of non-absorbable sutures or Tackers?].
AB  - AIM: Description and evaluation of ligamentopexy techniques using strings and
      spiral staples. MATERIAL AND METHODS: We first describe the ligamentopexy
      procedure using non-absorbable sutures before comparing this technique to the use
      of Tacker type staples. We describe the advantages and disadvantages of this
      procedure in terms of surgical technique, secondary complications and
      biomechanical strength. RESULTS: For our team, recommendable attitude is to use
      non-absorbable sutures for the fixation to the prevertebral ligament. The main
      advantages of the use of staples are the ease and facility for learning the
      technique. The risk of spondylodiscitis is rare but enhanced by the deeper
      penetration of the staples into the intervertebral discs. In terms of resistanc,
      promontofixation using sutures is much stronger compared to staples. CONCLUSION:
      The use of sutures for promontofixation, in laparoscopy, is preferred to the
      utilization of staples type Tacker. These staples should be used when there is a
      risk of needle stitches for the patient.

PMID- 14593299
TI  - [Adnexal torsion: a report of 135 cases].
AB  - OBJECTIVES: To evaluate the clinical findings and therapeutic options following
      adnexal torsion. STUDY DESIGN: A retrospective series of 135 patients presenting
      with adnexal torsion between January 1992 and December 2001 in Sousse- Tunisia- a
      university teaching hospital. RESULTS: Adnexal torsion accounted for 14.8% of
      surgically treated adnexal tumors. Pregnancy was associated in 17% of cases and
      diagnosis was accurate at first clinical examination in only 57.8% of cases.
      Ultrasound allowed visualisation of Adnexal Diseases in all cases. Operative
      laparoscopy was successfully achieved in 34% of patients. Conservative management
      was used in 57% of the premenopausal patients. No major postoperative
      complication was noted. CONCLUSION: Clinicians must be aware of a possible
      adnexal torsion in women with acute pelvic pain. Ultrasound is a useful tool in
      these situations. Laparoscopy allows diagnosis and surgical management even
      during pregnancy.

PMID- 14593298
TI  - [Accuracy of conservative treatment for infiltrating lobular breast cancer: a
      retrospective study of 217 infiltrating lobular carcinomas and 2155 infiltrating
      ductal carcinomas].
AB  - OBJECTIVES: Prognosis factors used for the management of infiltrative lobular
      carcinoma (ILC) are not different from those for infiltrative cuctal carcinoma
      (IDC). The aim of our work was to evaluate indications for conservative treatment
      for patients with ILC and to compare the results to those of patients with IDC.
      MATERIAL AND METHODS. Between 1985 and 1999 we retrospectively compared cases of
      217 ILC with cases of 2155 IDC treated in Centre Rene Gauducheau, Nantes.
      RESULTS: Clinical size of tumors was not different between ILC and IDC but
      pathological size>30 mm was more frequent for IDC. Good prognosis factors as
      pathological SBR classification I or II, positive hormone receptor, and the lack
      of axillary lymph node involvement, were more frequent for ILC. Clinical
      examination underestimated tumor size more frequently of ILC than IDC (p=0.02).
      Secondary mastectomy for involved margin was more frequent for ILC than IDC
      (p=0.001). For tumor with good prognosis factors, such as T<20mm, lack of lymph
      node involvement and SBR I or II with conservative treatment, 5 years local
      relapse were less frequent for ILC than IDC (p=0.025). CONCLUSION: Parameters to
      validate conservative or radical treatment are the same for ILC and IDC.
      Diagnosis of ILC should not influence decisions regarding surgical treatment.

PMID- 14593300
TI  - [Importance of thrombocytopenia for the management of HELLP syndrome: a report of
      104 cases].
AB  - OBJECTIVES: To evaluate the importance of thrombocytopenia in the management of
      HELLP syndrome (hemolysis, elevated liver enzymes, low platelet count). MATERIALS
      AND METHODS: This retrospective study included all patients with HELLP syndrome
      treated in the three departments of the Pellegrin Maternity Hospital in Bordeaux,
      between January 1993 and December 2001. One hundred and four patients were
      included and were divided into two groups according to the severity of
      thrombopenia: group 1 (platelet count<50000/mm(3)) and group 2 (50000<platelet
      count/mm(3)<100000). RESULTS: In group 1 complications occurred in 79% of cases
      and thrombocytopenia put patients at-risk for serious or life-threatening
      bleeding complications mainly in this group. CONCLUSION: It is crucial to class
      patients according to severity of thrombocytopenia, on admission. Termination of
      pregnancy should be considered for patients included in group 1. The other
      patients are best managed conservatively (depending on gestational age).

PMID- 14593301
TI  - [Conservative treatment of placenta accreta].
AB  - OBJECTIVE: Examination of modalities and results of conservative treatment of
      placenta accreta. MATERIAL AND METHOD: Ten-year hospital records were reviewed,
      with analysis of patients who had diagnosis of placenta accreta associated with
      conservative treatment. RESULTS: During the study period, 21259 deliveries were
      registered, with an incidence of placenta accreta of 1 per 1 000 deliveries
      (n=23). Conservative treatment was applied in 13 patients. All of them had
      factors commonly associated with placenta accreta: prior cesarean sections
      (7/13), prior curettage or endouterine surgery (11/13), placenta praevia (11/13).
      Antenatal diagnosis was performed in only 64% of the cases (n=7). In our
      conservative strategy, placenta accreta was always left in situ, with an
      associated treatment in most of cases (n=10): Bilateral hypogastric artery
      ligation (n=7), medical treatment with methotrexate (n=5), uterine artery
      embolization (n=2). There was no case of maternal mortality. Conservative
      treatment was successful in 11 patients. It failed in 2 cases: hysterectomy was
      performed in one case for life-threatening hemorrhage, and in the other case for
      post-embolization uterine necrosis. The morbidity described was blood transfusion
      (n=7), endometritis (n=1), and one late hemorrhage with expelling necrotic
      tissue. Afterwards, 2 women became pregnant: one miscarriage and one normal term
      delivery. CONCLUSION: Conservative treatment of placenta accreta appears to be a
      efficient way to preserve fertility. Antepartum diagnosis should be improved
      among patients with a high risk of placenta accreta in order to optimize
      conservative strategy.

PMID- 14593302
TI  - [Bacterial flora in the genital tract the last trimester of pregnancy].
AB  - Very widespread in our clinical setting, early-onset sepsis is due to organisms
      that commonly colonize or infect the maternal genital tract; identifying such
      organisms would help improve prevention and treatment. OBJECTIVE: To determine
      the bacterial ecology and the pathological status of the genital organs during
      the last trimester of pregnancy, in order to evaluate the risk of materno-fetal
      infections and to improve the present prophylactic measures based on monitoring
      bacterial carriage during the first trimester. METHOD: Vaginal and endocervical
      samples, usually taken during the first trimester of pregnancy were delayed and
      taken during the last trimester of pregnancy, in patients with no signs of sepsis
      and not taking antibiotics. A macroscopic examination described the aspect of the
      vagina, the cervix uteri, leukorrhea and possible inflammatory lesions or
      ulcerations. A microscopic examination searched for parasites, epithelial cells,
      Clue cells and leukocytes. The appropriate bacteriological cultures were
      performed after reading the Gram stain and scoring the vaginal flora. The
      clinical and cytobacteriological aspects were used to identify the bacterial
      ecology and the pathological genital states. RESULTS: Genital samples were
      collected from 306 pregnant women. Among them 118 were at 29-32 weeks of
      gestation, 104 at 33-36 and 84 at 37-40. The most frequent germs were C. albicans
      (33.3%), Enterobacteriaceae (20.3%) including E. coli (10.9%), S. aureus (15.4%),
      Gardnerella (13.6%), and Trichomonas (10.6%), in monomicrobian (79.2%) or
      polymicrobian carriage (20.8%). Lower genital tract pathological states such as
      vaginitis (29.4%), bacterial vaginosis (21.5%) or cervicitis (10.4%) and
      asymptomatic bacterial carriage (23.5%) and normal genital flora (15%) were
      identified. CONCLUSION: This is the first report of genital bacterial carriage in
      African women during the last trimester of pregnancy. Larger studies are required
      to evaluate the risk of maternofetal infections and to improve current
      prophylaxis measures.

PMID- 14593303
TI  - [Three-way prosthetic repair of the pelvic floor].
AB  - We describe the triple operation for prolapse with prosthesis in patients with
      pelvic organ prolapse using a vesicovaginal mesh for the cystocele, a
      rectovaginal mesh for the rectocele and a posterior retro-and trans levatory
      vault suspension sling. Preliminary results in a consecutive series of 92
      patients who underwent surgery between June 2001 and December 2002 showed three
      cases of vaginal erosion in contact with the prosthetic material, and one
      hematoma of the pararectal fossa with secondary abscess formation requiring
      ablation of the implant. There was one immediate anatomic failure. Function was
      good with no reports of dyspareunia or dyschesia.

PMID- 14593304
TI  - [Abdomino-pelvic leiomyoma of the round ligament: contribution of computed
      tomography and magnetic resonance imaging].
AB  - A case of bulky abdomino-pelvic leiomyoma of the round ligament is reported with
      the CT (computed tomography) and MRI (magnetic resonance imaging) findings.
      Leiomyoma appeared as encapsulated heterogeneous tumor on the spontaneous
      contrast CT images and on post-gadolinium contrast MRI. Lack of specificity
      hinders diagnosis before surgery. Leiomyoma of the round ligament is the most
      frequent histological type among round ligament tumors. Leiomyoma of the round
      ligament must be retained as a possible etiology of inguinal mass or pelvic
      tumor.

PMID- 14593305
TI  - [Management of meconium peritonitis: a remarkable case of idiopathic meconium
      peritonitis diagnosed antenatally].
AB  - Meconium peritonitis is an inflammatory peritonitis induced by meconium extruding
      into the peritoneal cavity through a perforation of the fetal intestine.
      Antenatal diagnosis is possible. Prognosis depends on the pathology having caused
      perforation. This is often unknown. The objectives of this article are to analyze
      the contribution of antenatal investigations to estimating neonatal prognosis of
      meconium peritonitis, and to define optimal management. We describe a case of
      meconium peritonitis diagnosed in utero with particularly severe ultrasound
      presentation suggesting a potentially lethal course for the neonate. An eutrophic
      infant was delivered vaginally after preliminary aspiration of the meconium
      ascites. The neonate presented with a very distended abdomen and responded well
      to neonatal resuscitation. Laparotomy exploration confirmed the diagnosis of
      meconium peritonitis. No cause was identified. No obvious perforation was found.
      The postsurgery period was uneventful. At later follow-up the infant was doing
      well, free of further problems notably of any digestive disorder. Antenatal
      ultrasound features suggestive of severe meconium peritonitis are distended fetal
      bowel loops, huge cystic masses, major meconium ascites, and polyhydramnios.
      These neonates have a high risk of obstruction and intestinal perforation.
      Intestinal resection is frequently required. Cardiopulmonary resuscitation is
      necessary more often in these neonates with a higher risk of fatal outcome due to
      respiratory distress syndrome or surgery complications. Prognosis remains good
      after antenatal diagnosis for neonates free of cystic fibrosis, providing
      delivery takes place in a center with adequate technical facilities.

PMID- 14593307
TI  - The catastrophic antiphospholipid syndrome--Asherson's syndrome.

PMID- 14593308
TI  - [Celiac disease and autoimmune diseases or systemic disease. Six cases and a
      review of the literature].
AB  - BACKGROUND: Celiac disease is an autoimmune disorder which may be associated with
      another autoimmune or systemic disease. OBJECTIVE: To determine the links between
      autoimmune diseases and celiac disease. PATIENTS AND METHODS: Among 31 patients
      with a celiac disease, we selected those who had another autoimmune or systemic
      disease. RESULTS: We report 6 patients with such disease association: 3 with
      autoimmune thyroiditis including one also with Grave's disease, 2 with systemic
      lupus erythematosus including one also with insulin-dependent diabetes mellitus,
      and 1 with temporal arteritis. CONCLUSION: The link between celiac disease and
      autoimmune thyroiditis or insulin-dependent diabetes mellitus seems to be real
      but many discrepancies are observed for the other autoimmune diseases. After a
      literature review, we suggest a summary of effective associations between celiac
      disease and autoimmune or systemic diseases.

PMID- 14593309
TI  - [Simultaneous hepatitis B virus infection and polyarteritis nodosa. Three cases].
AB  - In polyarteritis nodosa (PAN) due to hepatitis B virus (HBV) infection, the
      insidious nature of the infection makes very difficult to establish the
      chronology which often remains unknown. PN occurs in the majority of patients
      during the year following infection. Simultaneous occurrence or occurrence
      immediately after infection with the HBV is exceptional. We report here three
      cases of this form of simultaneous HBV infection and PN and describe the
      particular clinical, virological and evolutive features of the disease.

PMID- 14593311
TI  - [From back pain to life-discontent. A holistic view of psychopathological
      contributions to pain].
AB  - Back pain is a common and disabling condition; it afflicts young adults, and
      often pursues a chronic course--representing a major public health problem. The
      physical component of such pain is often overestimated. This paper describes five
      cases demonstrating how somatic factors can interact with psychological and
      psychiatric factors--i.e. the 'psychoaffective context'--to determine the degree
      of perceived pain. In a schema, we summarize the three ways in which the
      psychoaffective context may contribute to pain: i) physiologically, as a result
      of increased arousal, leading to muscle tension and perceptual hypervigilance,
      ii) emotionally, as a result of anxiety leading to stress and feeling of threat,
      and iii) cognitively, as a cognitive bias caused by increased attention to
      signals from the target region, and by an increased tendency to interpret these
      signals as aversive. Personality factors, autobiographical memory, and the place
      devoted to the body within the narcissistic equilibrium contribute to the degree
      of anxiety and cognitive bias. Moreover, anxiety and the cognitive bias are also
      exacerbated by the depressive syndrome that often accompany such pain.
      Collectively, these factors can lead to a somatization disorder and to chronic
      pain, even in response to an experience of minimal pain.

PMID- 14593310
TI  - [Are anxiety disorders more frequent in subjects with eating disorders?].
AB  - OBJECTIVE: We designed a controlled study comparing referred women with an eating
      disorder (ED) to a matched normal control group to answer the following
      questions: what are the frequencies of anxiety disorders (AD) in anorexia nervosa
      (AN) and bulimia nervosa (BN), according to DSM-IV criteria? Are AD significantly
      more frequent among women with an ED than among women from the community? METHOD:
      We assessed frequencies of six specific AD among 271 women with a current
      diagnosis of AN or BN and 271 controls, using the Mini International
      Neuropsychiatric Interview (MINI), French DSM-IV version. RESULTS: Seventy-one
      percent of both the AN and the BN subjects had a lifetime comorbidity with at
      least one AD, significantly more (p<0.001) than the percentage of controls with
      an AD. Prevalence was significantly higher in the ED groups than in controls for
      most types of AD, and between 41.8% and 53.3% of comorbid cases had an AD
      preceding the onset of the ED. CONCLUSION: Evidence that AD are significantly
      more frequent in subjects with ED than in the community has important etiological
      and therapeutic implications.

PMID- 14593312
TI  - [Post-traumatic stress disorder treatments].
AB  - A traumatic event (assault, traffic accident, bomb attack or war, disasters.) is
      often followed by a reaction of fear and anxiety which can evolve to a
      posttraumatic stress disorder (PTSD). Its severity and associated handicap
      justify treatment as early as possible. We present the various PTSD treatments
      and discuss their respective efficiency and limitations. Most of available
      treatments (cognitive and behavioral therapies, antidepressants.) are efficient
      on PTSD and co-morbid disorders. However, the efficiency of some therapies (eye
      movement desensitization) on the treatment of PTSD are controversial. Studies are
      necessary to evaluate various treatment strategies, optimal duration of
      antidepressant treatment and pediatric therapies.

PMID- 14593313
TI  - [Recurrent pregnancy loss related to immune disorders].
AB  - Progress in immunologic methods and diagnostic assays over the last two decades
      has led the description of an association between some cases of recurrent fetal
      loss and recurrent spontaneous abortion of unknown cause to immunological
      factors. Some causal immunological diseases or dysregulations have been
      identified in pregnant women. These abnormalities may precede or be triggered by
      the pregnancy, or occasionally result from an impairment of the mother's
      allogeneic response to the fetus. In this article we review the principal
      immunological factors and abnormalities implicated in recurrent pregnancy loss
      and focusing on those generally accepted by the majority of authors.

PMID- 14593314
TI  - [Constrictive pericarditis as first manifestation of neoplasia. Two cases].
AB  - We report two cases of constrictive pericarditis revealing neoplasia. Both
      patients underwent pericardiotomy with drainage and biopsy that did not disclose
      malignancy. Likewise, the initial radiologic were not suggestive of cancer.

PMID- 14593315
TI  - [An unusual cause of pancytopenia: intravascular lymphoma].
AB  - We report an observation of intravascular lymphoma occurring in a 69-year-old
      woman. This relatively rare disease presents polymorphic clinical features that
      render diagnosis difficult. Cutaneous and central nervous system signs and
      symptoms are frequently observed and should be recognized as suggestive of
      intravascular lymphoma. However, they are not always observed, in our case only
      pancytopenia was present. Pronostic is generally unfavorable but good response to
      chemotherapy has been described with early diagnosis. A large number of
      pathogenic hypotheses have been put forward: abnormality of cellular receptor,
      role of Epstein-Barr virus or transformation from lymphoma. Intravascular
      lymphoma should be included in the differential diagnosis of pancytopenia to
      increase chances of good response.

PMID- 14593316
TI  - Renal manifestations of tuberous sclerosis complex.
AB  - Tuberous sclerosis complex (TSC) is an autosomal-dominant neurocutaneous disorder
      involving the skin, brain, kidney, heart and other organs. Renal manifestations
      are mainly angiomyolipomas, renal cysts and cancer. We report three female
      patients, mean aged of 31 years (range: 22-37), with a family history of TSC in
      one case. Cutaneous and nervous symptoms were found in all patients. Clinical
      complaints were mainly abdominal pain (3 cases), hematuria (2 cases), right flank
      palpable mass (1 case). Angiomyolipomas (AML) were diagnosed by ultrasonography
      in all patients, associated to renal cysts in one case. A patient underwent total
      right nephrectomy without any event during the follow-up. In a second patient, a
      selective arterial embolization of AML was indicated. Total left nephrectomy was
      performed due to the persistence of hematuria and the increased flank mass.
      Pathological examination of the kidney revealed a clear cell carcinoma. The third
      patient with small AML, associated with renal cysts, required careful monitoring.
      Renal manifestations in TSC are frequent and serious, they are the second leading
      cause of death after nervous lesions. Clinical and morphological aspects are
      variable and different therapeutic indications must be discussed.

PMID- 14593317
TI  - [Management of the emphysematous pyelonephritis].
AB  - We report two cases of emphysematous pyelonephritis in diabetic patients. The
      first suffered from emphysematous pyelonephritis and emergency nephrectomy was
      performed. The second patient suffered from emphysematous pyelitis and was
      successfully treated by nephrostomy. We present a comprehensive review of the
      literature on emphysematous pyelonephritis and discuss the indications and the
      results of treatments of this rare and severe infection.

PMID- 14593320
TI  - [The knowledge required for imaging the pelvic organ].

PMID- 14593318
TI  - [Lemierre syndrome: unusual, but still possible].
AB  - Lemierre syndrome is a rare disease, which was life-threatening before the
      antibiotics era. We report here two cases with favorable outcome. Clinical
      features are stereotypic: tonsillis, cervical pain revealing deep vein
      thrombosis, and pulmonary septic metastasis. The most frequent causal germ on
      blood cultures is Fusobacterium necrophorum but other anaerobial bacteries can be
      found. Cervical Doppler-ultrasonography, and thoracic tomodensitometry are
      useful. Medical treatment is antibiotic therapy and anticoagulation.

PMID- 14593321
TI  - [MR angiography (MRA)].

PMID- 14593322
TI  - [Improving oral presentation of research reports].

PMID- 14593323
TI  - [About the Yakuji regulation of the electromagnetic compatibility (EMC)
      performance of medical electrical devices].

PMID- 14593324
TI  - [Reports on the 59th Congress of Japanese Society of Radiological Technology].

PMID- 14593325
TI  - [Reports on the 59th Congress of Japanese Society of Radiological Technology].

PMID- 14593326
TI  - [Reports on the 59th Congress of Japanese Society of Radiological Technology].

PMID- 14593327
TI  - [New hope for winning the war against cancer: IMRT=Intensity-Modulated-Radiation
      Therapy--part 5-].

PMID- 14593329
TI  - [Construction of DICOM-WWW gateway by open source, and application to PDAs using
      the high-speed mobile communications network].
AB  - The author constructed a medical image network system using open source software
      that took security into consideration. This system was enabled for search and
      browse with a WWW browser, and images were stored in a DICOM server. In order to
      realize this function, software was developed to fill in the gap between the
      DICOM protocol and HTTP using PHP language. The transmission speed was evaluated
      by the difference in protocols between DICOM and HTTP. Furthermore, an attempt
      was made to evaluate the convenience of medical image access with a personal
      information terminal via the Internet through the high-speed mobile communication
      terminal. Results suggested the feasibility of remote diagnosis and application
      to emergency care.

PMID- 14593328
TI  - [Questionnaire survey on teleradiology for radiological technologists: analyses
      by age group and facility type in Hokkaido].
AB  - A questionnaire survey was given to 1,951 radiological technologists in Hokkaido
      to examine their views on teleradiology. The questionnaire consisted of questions
      about their understanding of teleradiology and interest in it as well as
      examining the need for teleradiology and problems with it. A total of 1,275
      radiological technologists responded to the survey, a response rate of 65.4%. The
      returned questionnaires were analyzed according to different groups categorized
      by age of the radiological technologists and type of medical facility. Almost all
      radiological technologists knew about teleradiology. Among the different age
      groups, the higher age groups showed greater recognition and understanding of
      teleradiology. About 60% of radiological technologists were interested in
      teleradiology (no significant differences among age groups). When it was assumed
      that a teleradiology system would be introduced, (1) the working load for
      radiological technologists was estimated to be about 17,820 (+/-24,233) yen per
      month. (2) Sixty percent of the respondents considered that the system should be
      used for the reading and diagnosis of difficult cases. (3) Fifty percent of them
      thought that the system should be managed and operated by radiological
      technologists. (4) Many radiological technologists pointed out problems
      concerning initial costs and the facility's management system.

PMID- 14593330
TI  - [Examination of measurement and its method of compensation of the sensitivity
      distribution using phased array coil for body scan].
AB  - The influence on the quality of images by measurement of a sensitivity
      distribution and the use of a sensitivity compensation filter was considered
      using an opposite-type phased array coil and volume-type phased array coil. With
      the opposite-type phased array coil, the relation between coil interval and
      filter was investigated for the IIC filter, SCIC filter (GE), and the Normalize
      filter (SIEMENS). The SCIC filter and Normalize filter showed distance
      dependability over the coil interval of SNR and uniformity was observed, and the
      existence of an optimal coil interval was suggested. Moreover, with the IIC
      filter, distance dependability over a coil interval was small, and the decrease
      in contrast with use was remarkable. On the other hand, with the volume-type
      phased array coil, the overlap of an array element was investigated to determine
      the influence it had on sensitivity distribution. Although the value stabilized
      in the arrangement center of an array element, and its near, was shown when
      volume-type phased array coil was used, SNR and uniformity decreased as it
      separated from the center. This showed that overlap of an array element does not
      have an adverse influence on image quality when the already optimized arrangement
      is used.

PMID- 14593331
TI  - [Investigation of beam quality for digital chest radiography with RbBr:Tl(+)
      photostimulable storage phosphors].
AB  - Beam quality for digital chest radiography in digital radiography systems (DR
      systems) with RbBr:Tl(+) photostimulable storage phosphors was investigated.
      Measurements of overall Wiener spectrum (overall WS) and observer performance
      experiments by means of Scheffe's method of paired comparisons were performed
      under the same exposure (5.16x10(-7)C/kg) at the X-ray detector of DR systems
      (sampling distance: 175 micro m, 2,048x2,048 pixels, 12 bits, look-up table:
      THX2) with a phantom lung and metacryl plates. Overall WS values were indicated
      to be inferior at higher tube voltages. All of the overall WS values were greater
      than those of screen film systems (HGM/UR1:S/F) at radiographic density 0.50,
      which was considered the density of the mediastinum and the area below the
      diaphragm (low density area), and at radiographic densities 1.00 and 1.50,
      considered as lung, WS values of S/F were located between the overall WS values
      of 80 kV and 100 kV, and 120 kV and 140 kV, respectively. Evaluation of
      visibility including mediastinum, lung, and total were indicated to be superior
      at the lower tube voltages. In evaluation of the mediastinum, the base image,
      which was obtained by 100 kV tube voltage (effective energy: 46.0 kV) in this
      study, was not significant from 90 kV to 110 kV tube voltages (range, +/-10 kV),
      and in-lung and total evaluations were not significant from 90 kV to 120 kV
      (range, -10 kV to +20 kV), and from 80 kV to 120 kV (range, +/-20 kV) tube
      voltages by 99% confidence interval. In conclusion, optimal beam quality for
      digital chest radiography with RbBr:Tl(+) photostimulable storage phosphors was
      considered to be less than 110 kV tube voltage (effective energy, 47.9 keV) in
      0.1 mm copper and 3.8 mm aluminum total filtration. In this case, the granularity
      in low-density areas were inferior to those of S/F systems but nearly equal to
      the middle and high-density areas of chest images, and exposure dose was 14.3%
      lower than that of the base image obtained by 100 kV (effective energy, 46.0 keV)
      tube voltage in this study.

PMID- 14593332
TI  - [Gastric functions using capsules containing contrast medium: characteristics in
      patients with esophagitis].
AB  - We studied gastric function in patients with functional dyspepsia, using capsules
      containing contrast medium. We were able to estimate intragastric capsule
      movement by this method. Here, we report gastric functions in patients with
      esophagitis. We were able to recognize gastric dysfunction (delayed gastric
      emptying) in these patients.

PMID- 14593333
TI  - [Radiation management for infectious waste from nuclear medicine studies].
AB  - An industrial waste management service has refused to collect medical waste from
      our hospital owing to radioactive contamination found in the waste in July 2000.
      An investigation revealed that the "three-way stopcock" and handling diapers used
      for radioisotope examination were the radioactive contaminants. We therefore
      reconsidered the system of medical waste maintenance especially for radioactive
      materials. Since February 2001, we have resumed radiation maintenance by
      following the manual for the handling diapers of patients administered
      radiopharmaceuticals issued by five organizations associated with JRS, JSRT,
      JSNM, JSNMT, and JARPM. A major change was to check the radioactive waste at the
      individual departments and at a centralized check system. This eliminated the
      problem of dumping radioactive material into medical waste as well as resolving
      the concerns of the industrial waste management service.

PMID- 14593341
TI  - The management challenge: making the most of your next performance appraisal.

PMID- 14593342
TI  - U.S. Supreme Court to review drug addiction case.

PMID- 14593343
TI  - Complementary or alternative medicine and cardiovascular health.

PMID- 14593346
TI  - Implementing an early intervention case management program in three medical
      groups.

PMID- 14593347
TI  - The physician/case manager partnership revisited.

PMID- 14593348
TI  - Consensus paper of the 2003 Physician and Case Management Summit: exploring best
      practices in physician and case management collaboration to improve patient care.

PMID- 14593349
TI  - Collaboration between physicians and case managers.
AB  - Physicians and case managers are key stakeholders in the health care system. To
      foster collaboration between these occasionally opposing groups, the Case
      Management Society of America and Professional Resources in Management Education
      Inc. held a summit in Miami on April 4, 2003, to bring representatives from each
      group face to face. Attendees explored many barriers and opportunities involved
      in achieving and maintaining collaboration.

PMID- 14593350
TI  - Challenges in assessing costs of rheumatoid arthritis.

PMID- 14593351
TI  - [Clinical, hemodynamic and neurohumoral effects of long-term therapy of patients
      with severe chronic heart failure with beta-adrenoblocker bisoprolol].
AB  - The use of beta-adrenoblockers in conjunction with angiotensin converting enzyme
      inhibitors improves quality of life and prognosis of patients with chronic heart
      failure. However basic mechanisms of these positive effects in severe heart
      failure remain to be elucidated. METHODS: Patients (n=54) with NYHA class III-IV
      heart failure and left ventricular ejection fraction < or =35% were randomized
      either to treatment with bisoprolol (1.25-10 mg/day) (n=30) or in control group
      (n=24) and were followed up for 12 months. RESULTS: The use of bisoprolol was
      associated with significant improvement of heart failure functional class,
      lowering of heart rate (by 14%, p<0.01), elevation of systolic blood pressure (by
      7.2+/-12.3 mm Hg, p<0.01) and increase of walking distance (by 30.1+/-29.0 m,
      p<0.01). No significant changes of these parameters occurred in control group.
      After 12 months increases of left ventricular end diastolic and end systolic
      volumes (by 85+/-69.2 and 71+/-51.5 ml, respectively, p<0.001) and of ejection
      fraction (by 5.7+/-7.3%, p<0.01) took place in bisoprolol treated patients. These
      changes were significantly (p<0.001) higher than those in control group. After 6
      months of treatment with bisoprolol noradrenaline concentration fell from 533 to
      402 pg/ml (p<0.05) while in controls it rose from 369 to 474 pg/ml, p<0.01).
      Decreases of plasma renin activity (from 1.2 to 0.42 ng/ml/h), plasma
      concentrations of angiotensin II (from 17.1 to 13.1 pg/ml) and aldosterone (from
      173 to 148 pg/ml, p<0.05) were also observed in bisoprolol group. No substantial
      dynamics of activity of main components of renin angiotensin system took place in
      controls. There were no significant changes of atrial natriuretic peptide in both
      groups. Significant positive dynamics of parameters of heart rate variability was
      registered only in bisoprolol group: SDNN increased by 25% (p<0.05), high
      frequency spectrum by 106% (p=0.03), LF/HF ratio from 2.18+/-1.41 to 1.82+/-0.7.
      CONCLUSION: Long term use of bisoprolol was associated with improved clinical and
      hemodynamic status, increased systolic BP, blocked processes of pathological left
      ventricular remodeling, lowered activity of not only sympathetic-adrenal but also
      of main components of renin-angiotensin system and improved heart rate
      variability.

PMID- 14593352
TI  - [Intraventricular filling flows in assessment of left ventricular diastolic
      function in the elderly].
AB  - AIM: To assess effect of old age on Doppler parameters of intraventricular
      filling flows. MATERIAL: Echocardiography with determination of velocity and time
      of early diastolic flow propagation, degree of its deceleration, maximal regional
      intraventricular flow velocity, and late diastolic interval A-Ar was carried out
      in healthy elderly (age 68.0+/-7.5 years, n=20) and middle aged (mean age 45.9+/
      5.9 years, n=20) persons. RESULTS: Elderly compared with middle aged persons had
      decreased velocity (42.1+/-1.6 and 57.6+/-0.9 cm/sec, respectively, p=0.0001) and
      prolonged time (29.3+/-4.3 and 18.4+/-2.2 ms, respectively, p=0.02) of
      intraventricular early diastolic flow propagation, lower Eiv (0.64+/-0.04 and
      0.92+/-0.04 ms, respectively, p=0.0001) and E(iv)/E (0.85+/-0.04 and 1.14+/-0.07,
      respectively, p=0.006), similar A-Ar (55.2+/-3.5 and 0.54+/-0.04 ms,
      respectively, p=0.78). CONCLUSION: Advanced age is associated with worsened
      active relaxation of the myocardium which is not accompanied by substantial
      changes of late diastolic left ventricular stiffness.

PMID- 14593353
TI  - [Relationship between Chlamydia pneumoniae and classical risk factors of coronary
      heart disease].
AB  - In order to elucidate relationship between Chlamydia pneumonia infection and
      established risk factors of coronary heart disease (hypercholesterolemia,
      hyperglycemia, hyperfibrinogenemia, smoking, age) chlamydial IgA and IgG
      antibodies were determined by solid phase enzyme immunoassay in 122 patients with
      ischemic heart disease and 40 healthy subjects. Elevated titers of IgA class
      antibodies were found to be associated with presence of ischemic heart disease as
      well as with hypercholesterolemia, hyperglycemia, hyperfibrinogenemia, and
      smoking.

PMID- 14593354
TI  - [Effectiveness of excimer laser coronary angioplasty in treatment of patients
      with in-stent restenosis].
AB  - In-stent restenosis (ISR), when treated with balloon angioplasty (PTCA) alone,
      has an angiographic recurrence rate of 30-85%. Ablating the hypertrophic
      neointimal tissue prior to PTCA is an attractive alternative, however late
      outcomes of such treatment have not been fully determined. This multicenter case
      control study assessed angiographic and clinical outcomes of 137 consecutive
      procedures in 125 patients treated for ISR with either PTCA alone (n = 58) or
      excimer laser assisted coronary angioplasty (ELCA, n = 67). Demographics were
      similar. Lesions selected for ELCA compared with those selected for ?PTCA were
      longer (17.1+/-9.9 mm vs. 13.6+/-9.1 mm; p=0,034), more complex (ACC/AHA type C:
      36,5% vs. 14,3%; p=0,006), and with reduced antegrade flow (TIMI flow < 3: 18,9%
      vs. 4,8%; p = 0,025). ELCA- and PTCA treated patients had similar rates of
      procedural success (98,5 and 98,3%, respectively, p=1,0), major clinical
      complications (3,0% and 8,6%; respectively, NS), major cardiac events at 1 year
      (37,3 and 46,6%. respectively, NS), and target lesion revascularization (32,8
      and. 34,5%; respectively, NS). These data suggest that ELCA in patients with
      complex in-stent restenosis is as safe and effective as PTCA. Despite higher
      lesion complexity in ELCA-treated patients, no increase in event rates was
      observed.

PMID- 14593355
TI  - [Reperfusion syndrome after direct myocardial revascularization on beating heart
      in patients with ischemic heart disease. Possibilities of prevention with
      amlodipine].
AB  - Possibilities of secondary prevention of reperfusion syndrome with amlodipine was
      assessed in 46 patients (39 with class III-IV angina after myocardial infarction
      and 7 with non ST elevation acute coronary syndrome). Twenty six patients
      received basic therapy, in 20 patients this therapy was supplemented with
      amlodipine (5-10 mg/day). In all patients complete direct arterial myocardial
      revascularization on beating heart was carried out. Methods of dynamic control
      included echocardiography, paired bicycle exercise tests, 6 minute walk test,
      myocardial scintigraphy with thallium-199. The results evidence for efficacy and
      feasibility of secondary prevention of reversible myocardial dysfunction with
      amlodipine.

PMID- 14593356
TI  - [Non ST elevation acute coronary syndrome. Some characteristics of coagulation
      and von Willebrand factor during short term use of ticlopidine or clopidogrel].
AB  - Levels of some markers of coagulation and platelet activation such as prothrombin
      fragment 1+2 (F1+2) thrombin-antithrombin complex (TAT) and von Willebrand factor
      (vWF), are related to outcome in non ST-segment elevation acute coronary syndrome
      (NSTEACS). Effects of thienopyridines ticlopidine and clopidogrel on acute
      changes of these parameters in patients with NSTEACS are not well investigated.
      AIM: To study changes of markers of coagulation and platelet activation during
      short term use of ticlopidine and clopidogrel in NSTEACS patients treated with
      aspirin and antithrombin. METHODS: Patients with NSTEACS, treated with aspirin
      and unfractionated heparin (n=37, <48 hours from pain onset, Braunwald class
      IIIb) were randomized to open ticlopidine (n=19, 500 mg BID loading dose for 2
      days and 250 mg BID for subsequent 5 days) or no ticlopidine (n=18). In another
      substudy with the same design 19 aspirin and enoxaparin treated patients were
      randomized to clopidogrel (n=10, 300 mg loading dose and 75 mg/day for subsequent
      6 days) or no clopidogrel (n=9). Levels of F1+2, TAT and vWF were measured at
      baseline, on days 1, 3, 7 and 14 (7 days after discontinuation of
      thienopyridines). RESULTS: At baseline values of parameters studied were similar
      in each pair (thienopyridine - control) of patient groups. Compared with their
      controls ticlopidine treated patients in 7 days after ticlopidine discontinuation
      had lower levels of TAT (2.77 and 3.61 ng/ml, r<0.05) and fibrinogen (3.16 and
      3.84 g/l, r<0.05). The level of vWF in ticlopidine treated patients was lower
      relative to control group on days 3 (163 and 186%, r<0.05) and 14 (144 and 173%,
      p<0.01). In substudy with clopidogrel differences between groups existed only in
      vWF levels. In clopidogrel treated patients the level vWF was lower relative to
      controls on days 3 (152 and 185%, r<0.05) and 7 (141 and 166%, r<0.05).
      CONCLUSION: Short term use of ticlopidine in patients with NSTEACS treated with
      aspirin and unfractionated heparin was associated with lower levels of TAT and
      fibrinogen (relative to control group) on day 14. This could be interpreted as
      delayed effect of ticlopidine on thrombin activity. Both ticlopidine and
      clopidogrel used in regimes with loading doses in NSTEACS patients treated with
      aspirin and antithrombin prevented acute phase elevation of vWF.

PMID- 14593357
TI  - [Therapy of patients with arterial hypertension with fixed dose combination of
      losartan and hydrochlorothiazide. Effect on 24 hour blood pressure and left
      ventricular hypertrophy].
AB  - Twenty four hour blood pressure (BP) monitoring was carried out and structural
      state of left ventricular myocardium assessed in 20 patients with mild and
      moderate hypertension before and after 24 weeks of therapy with Hyzaar - fixed
      dose combination of losartan (50 mg) and hydrochlorothiazide (12.5 mg). According
      to data of 24-hour BP monitoring the use of Hyzaar was associated with lowering
      of diurnal (by 26.9/17.2+/-3/2 mm Hg, p<0.001), nocturnal (by 32.6/18.9+/-3/2 mm
      Hg, p<0.001), pulse (p<0.001) BP, and rate of morning systolic BP rise (p<0.05),
      decrease of nocturnal systolic and diastolic BP variability, and improvement of
      24-hour BP rhythm. Trough/peak coefficients for systolic and diastolic BP (70 and
      76%, respectively) reflected sufficient and steady hypotensive effect throughout
      24 hours after single dose of Hyzaar. Target BP level was achieved in 70% of
      patients. At the background of 24-week treatment with Hyzaar left ventricular
      myocardial mass index significantly decreased (from 120.1+/-3.5 to 108.6+/-3.1
      g/m2, D=11.5+/-1.0, p<0.001) and became normal in 60% of patients. Correlation
      analysis revealed independence of cardioprotective action of therapy from its
      hypotensive activity. Thus therapy with Hyzaar produced hypotensive and
      cardioprotective effects which were independent from each other.

PMID- 14593358
TI  - [The use of nebivolol in menopausal women with hypertension].
AB  - Nebivolol was given for 8 weeks to 34 menopausal women with grade 1 and 2
      hypertension. Monotherapy was effective in 66,7% of patients, while in other
      patients combination with hydrochlorothiazide (12.5 mg) was required. The use of
      nebivolol was associated with decreased rate and severity of vasomotion reactions
      and thus with positive effect on menopausal syndrome. Nebivolol appeared to be
      safe and metabolically neutral.

PMID- 14593359
TI  - [Ionic mechanisms of cardiotropic action of a new class III antiarrhythmic drug
      RG-2].
AB  - A perforated patch-clamp analysis of the effect of a novel class III
      antiarrhythmic agent RG-2, on voltage-dependent currents was made in rat
      ventricular myocytes. In these cells, RG-2 decreased delayed rectifier outward
      K(+) current, I(k), in concentration dependent manner with threshold
      concentration 0.1 microM/l. In contrast, the drug did not have significant
      effects on the transient outward and inward rectifier K(+) current. RG-2 in
      concentration dependent manner decreased Ca(2+) current (I(Ca,L)) with threshold
      concentration 1 microM/l, tenfold higher than threshold concentration for I(k).
      We can conclude that decreasing of I(k) may explain prolongation of cardiac
      repolarization induced by RG-2, and contribute to its antiarrhythmic action.

PMID- 14593360
TI  - [Neurocirculatory dystonia (does this disease exist?)].
AB  - Difficulties of diagnostics of neurocirculatory dystonia are discussed.
      Definition based on Myasnikov's ideas about hyperreactivity, that is inadequate
      cardiovascular responses to psychoemotional stress, is proposed. Peculiarities of
      classification and therapy of neurocirculatory dystonia are presented.

PMID- 14593361
TI  - [Left ventricular hypertrophy in hypertension. Part I. Criteria of diagnosis and
      prevalence].
AB  - Possibilities of electrocardiography, echocardiography and magnetic resonance
      tomography for diagnosis of left ventricular hypertrophy are reviewed and various
      criteria of left ventricular hypertrophy compared. Literature data concerning
      prevalence of left ventricular hypertrophy in different populations are presented
      and dependence of reported prevalences of left ventricular hypertrophy on
      diagnostic technique and criteria is demonstrated. Criteria of dynamic changes of
      left ventricular mass are also discussed.

PMID- 14593362
TI  - [The problem of assessment of efficacy of antihypertensive therapy using 24-hour
      blood pressure monitoring].
AB  - Main advantages of the use of 24-hour blood pressure (BP) monitoring for
      assessment of effects of antihypertensive therapy consist in more precise
      selection of patients requiring drug treatment and more objective evaluation of
      results of therapy. However methodological limitations also exist. Among them are
      susceptibility of results to regression to the mean, insufficient understanding
      of many characteristics of 24-hour BP profile, interdependence (co-linearity) of
      various parameters. Lack of convincing data on prognosis of patients whose
      antihypertensive treatment has been guided by 24-hour BP monitoring also presents
      a serious problem. Promising direction of further research is investigation of
      reproducibility and reliability of different parameters of BP monitoring in
      relatively short-term studies including those with surrogate end points.

PMID- 14593364
TI  - [Parameters of spectral-temporal maps of signal averaged ECG in patients with
      ischemic heart disease and chronic heart failure].
AB  - Signal averaged ECG was registered in 57 patients with chronic heart failure due
      to ischemic heart disease and either accelerating or stable class III effort
      angina. Analysis of parameters of spectral-temporal maps showed that high local
      activity in terminal portion of ventricular and atrial complexes reflected
      heterogeneity of depolarization of atrial and ventricular myocardium. These
      changes correlated with presence of atrial and ventricular late potentials and
      could be used as markers of electrical instability of the myocardium.

PMID- 14593363
TI  - [Results of international study of quality of life of patients with stable angina
      treated with nitrates (IQOLAN)].
AB  - Effect of transition from multiple administration of short acting nitrates to
      once daily use of isosorbide-5-mononitrate on angina class and quality of life
      was studied in 280 patients with stable angina pectoris. Transition to isosorbide
      5-mononitrate was associated with increases of (in units) exercise tolerance
      (Delta=-6.6+/-0.35, p<0.001), satisfaction from treatment (Delta=-2.1+/-0.12,
      p<0.001), degree of psychological discomfort (Delta=-2.8+/-0.21, p<0.001),
      decreases of numbers of attacks of angina (Delta=-4.0+/-0.22, p<0.001) and side
      effects (Delta=-4.1+/-0.29, p<0.001), increase of average distance of walking
      without chest pain or dyspnea (from 372.1+/-415.1 to 586+/-663.5 m), shortening
      of duration of episodes of angina (from 4.7+/-4.0 to 4.1+/-7.2 min), significant
      lowering of angina class (p<0.0001). Thus in patients with ischemic heart disease
      long acting formulation of isosorbide-5-mononitrate provided rapid onset and
      stability of therapeutic action what eventually resulted in effective prevention
      of attacks of angina and improvement of quality of life.

PMID- 14593365
TI  - [The role of transesophageal dopplerographical assessment of coronary reserve in
      coronary sinus in diagnosis of hemodynamically significant left coronary artery
      stenoses].
AB  - AIM: To assess the role of estimation of coronary reserve in coronary sinus by
      transesophageal doppler during dipyridamole stress test for diagnosis of
      hemodynamically significant left coronary artery stenoses. MATERIAL: Patients
      with angiographically proven left coronary artery stenoses (n=29) and 25 healthy
      volunteers. METHODS: Coronary reserve was calculated as 1) ratio of peak to basal
      diastolic coronary flow velocity (V(p)CR), and 2) ratio of volume coronary blood
      flow velocity before and during hyperemia (VBF CR). Coronary reserve <2 was
      considered decreased. RESULTS: Compared with healthy subjects patients with
      coronary heart desease had significantly lower V(p)CR (1.67+/-0.44 and 2.56+/
      0.87, respectively, p<0.001) and VBF CR (2.42+/-1.37 and 5.53+/-3.65,
      respectively, p<0.001). Sensitivity and specificity of coronary reserve below 2
      for diagnosis of left coronary artery stenoses was 72 and 72%, respectively, for
      V(p)CR, and 49 and 96%, respectively, for VBF CR. VBF CR below 2 was a marker of
      severe double vessel left coronary artery disease. V(p)CR <2 was associated with
      single vessel stenoses within left coronary artery system. CONCLUSION: The use of
      evaluation of coronary reserve by transesophageal dopplerography for diagnosis of
      left coronary artery stenoses is methodologically correct. Level of coronary
      reserve in coronary sinus can be considered an integral parameter characterizing
      total left coronary artery atherosclerotic damage.

PMID- 14593366
TI  - [Effect of acetyl-CoA C-acyltransferase inhibitor trimetazidine on parameters of
      global and local systolic and diastolic functions of left ventricular myocardium
      in patients with combined postinfarction ischemic syndrome].
AB  - AIM: To assess effect of trimetazidine on global and regional systolic and
      diastolic left ventricular function in patients with combined postinfarction
      ischemic syndrome. MATERIAL: Patients (n=32) with healed myocardial infarction
      and signs of global systolic (ejection fraction 38,5+/-2,7%) and diastolic
      (EIA=0,88+/-0,03) left ventricular dysfunction confirmed by Doppler
      echocardiography. METHODS: Regional systolic and diastolic function was assessed
      by dobutamine stress echocardiography with Doppler tissue imaging before and
      after 3 months during which the patients received 60 mg/day of trimetazidine.
      RESULTS: The segments with hibernating myocardium were found in every patient.
      These segments along with segments with scars displayed greatest degree of local
      systolic and diastolic dysfunction and because of their prevalence made
      significant contribution to the setting of global diastolic dysfunction.
      Improvement of global diastolic function at rest after trimetazidine was
      associated with decrease of total number of ischemic segments (from 80 to 67%)
      especially of those with hibernation (from 61 to 46%). CONCLUSION: The
      hibernating myocardium was most sensitive to metabolic intervention and its
      presence after myocardial infarction predicted improvement after drug treatment
      of not only systolic but also diastolic left ventricle dysfunction. Restoration
      of function of hibernating myocardium turned out to be possible not only after
      myocardial revascularization but also after medical therapy.

PMID- 14593368
TI  - [Immediate and remote results of left main coronary angioplasty].
AB  - Angioplasty of left main coronary artery stenosis with stent implantation in left
      main and anterior interventricular arteries was carried out in 7 patients. In 5
      patients standard methods were used while in 2 patients original technique
      developed in the Saratov Institute of Cardiology was employed. In 2 of 5 patients
      in whom standard method was used attempts to perform angioplasty of the
      circumflex artery stenosis were not successful.

PMID- 14593367
TI  - [Non-ST elevation acute coronary syndrome: changes of parameters of hemostasis
      during and after treatment with unfractionated heparin and enoxaparin].
AB  - AIM: To compare changes of parameters of hemostasis in patients with non-ST
      elevation acute coronary syndrome (NSTEACS) during and after treatment with
      unfractionated heparin (UFH) and low molecular weight heparin (LMWH) enoxaparin.
      MATERIAL: Control groups of 2 randomized studies of effects of thienopyridines in
      NSTEACS with similar inclusion criteria. METHODS: In patients (n=18) of study one
      UFH was infused intravenously for 54.2+/-22.3 h, in patients of study two
      subcutaneous enoxaparin 1 mg/kg b.i.d. was used for 76.2+/-28.3 h. Levels of D
      dimer (DD), thrombin-antithrombin complex (TAT), prothrombin fragment 1+2 (F1+2),
      von Willebrand factor (vWF), fibrinogen, tissue plasminogen activator (TPA) and
      activity of its inhibitor (PAI), soon after start of treatment with heparins and
      in 1, 3, 7 and 14 days. RESULTS AND CONCLUSION: Short term lowering of DD and TAT
      levels occurred during UFH infusion apparently reflecting primary antithrombin
      action of UFH. During LMWH use DD level remained unchanged however its lowering
      was observed after cessation of LMWH (on days 7 and 14). The use of LMWH was not
      associated with increases of thrombinemia (TAT), thrombin generation (F1+2), and
      fibrinogen which were registered after end of UFH infusion (days 3, 7 and 14).
      Neither UFH nor LMWH prevented acute phase vWF elevation. The use of both
      heparins was associated with changes that could be interpreted as
      profibrinolytic. In LMWH treated patients these changes (elevations of TPA level)
      became manifested early (on day 3) and were short lived while in UFH treated
      patients they appeared later (on day 7) and were prolonged (as lowered PAI
      activity on day 14).

PMID- 14593369
TI  - [Erythrocyte cholesterol content in polycythemia vera: relation to ischemic heart
      disease].
AB  - Relative cholesterol content and its distribution between erythrocytes and plasma
      were studied in 34 patients with polycythemia vera (PV) both with and without
      concomitant coronary heart disease (CHD). Deformability of erythrocytes,
      disturbances of microcirculation (blood flow fragmentation, decrease of capillary
      density) were also assessed. Erythrocytes cholesterol/phospholipids molar ratios
      (0.68+/-0.03) in patients was lower than normal value (0.8) in spite of decreased
      cell deformability. This was associated with some increase of peroxidation
      products. Blood cholesterol distribution between cell and plasma species had some
      peculiarities caused by high hematocrit: compared with normal value erythrocytes
      of patients carried relatively larger portion of total blood cholesterol (23.7+/
      0.8% and 27-31%, respectively). However in CHD patients these values were
      significantly lower with correspondent increase of plasma cholesterol quota. This
      allowed to suggest possible protective role of blood cholesterol redistribution
      in polycythemia patients, through erythrocytes trafficking of some part of plasma
      cholesterol.

PMID- 14593370
TI  - [Heart rate control with nebivolol in patients with tachysystolic atrial
      fibrillation].
AB  - AIM: To find out whether selective beta-adrenoblocker nebivolol can be used for
      heart rate (HR) control in patients with chronic tachysystolic atrial
      fibrillation. MATERIAL: Patients (n=20, 7 men, 13 women, age 47-79 years) with
      ischemic heart disease and permanent atrial fibrillation (duration 2.5 months -
      11 years) admitted to a specialized clinic for diagnosis and treatment of cardiac
      arrhythmias. All patients had tachycardia throughout 24 hours despite therapy.
      METHODS: Dosing of nebivolol: week 1 - 2.5 mg/day, week 2 7 5 mg/day. If after 2
      weeks HR was considered inadequate the dose was increased up to 7.5 mg/day.
      Holter ECG was registered at baseline and in the end of weeks 1 and 2 of
      treatment. RESULTS: After 1 week of nebivolol (2.5 mg/day) HR decreased: day-time
      average - from 116.3+/-13.4 to 97.2+/-14.5, day-time minimal - from 78.1+/-13,5
      to 71.4+/-8.2, day-time maximal - from 154.4+/-18.1 to 142.1+/-15.5; night-time
      average - from 83.6+/-7.1 to 76.3+/-7.14, night-time minimal - from 61.2+/-6.7 to
      56.6+/-5.1, night-time maximal - from 93.5+/-10.5 to 88.2+/-10.8 bpm. After week
      2 when patients received 5 mg/day of nebivolol their HR was: day-time average -
      79.6+/-9,8, day-time minimal -65.2+/-7.7, day-time maximal - 128.7+/-12,2, night
      time average - 69.9+/-7.6, night-time minimal - 53.1+/-4,7, night-time maximal -
      80.8+/-10.1 bpm. In 2 patients (10%), interruption of nebivolol was required
      because of atrioventricular block in evening and nocturnal periods. CONCLUSION:
      Nebivolol effectively controlled HR in hospitalized patients with chronic atrial
      fibrillation due to ischemic heart disease. In most patients 5 mg /day was
      sufficient for attainment of acceptable HR.

PMID- 14593371
TI  - [Electrophysiological experimental study of a novel class III antiarrhythmic drug
      RG-2].
AB  - The electrophysiologic effects of a new drug, RG-2 were studied on anesthetized
      open-chest dogs and on rabbit right atrial tissue. RG-2 was manufactured in
      Chemical-Pharmaceutical Institute in Moscow. Dogs (n=12) were anesthetized with
      sodium pentobarbital (30 mg/kg, i.v.). An ECG lead II, arterial blood pressure,
      His bundle electrogram, atrial and ventricular bipolar electrograms were
      continuously monitored, recorded and then analyzed by a computerized complex for
      electrophysiological study. Electrophysiological variables, ECG parameters,
      atrioventricular conduction (His electrogram) and blood pressure were determined
      after sequential i.v. administration of 1, 5, 10, 20, 40 and 80 ug/kg of RG-2.
      Interval between injections was 60 min. RG-2 had no significant effect on PQ,
      QRS, S-A, A-H and H-V intervals, but the drug caused dose-dependent increase of R
      R and QT intervals. Moreover, RG-2 dose-dependently increased the atrial and
      ventricular effective refractory periods (AERP and VERP). Maximal increases of
      AERP and VERP registered at 5 min after administration of RG-2 (40 microg/kg)
      were 46+/-2% (p<0.001 vs control) and 23+/-6% (p<0.05 vs control), respectively.
      In the isolated rabbit right atrial tissue RG-2 (0.01 to 1 microM) had no effects
      on maximal diastolic potential, action potential amplitude and Vmax, but revealed
      concentration-dependent increase of action potential duration at 90%
      repolarization level (APD90%). The maximal effects on APD90% obtained after RG
      superfusion at 1 microM were 26+/-7% (p<0.001 vs control). We conclude that RG-2
      has significant effects of class III antiarrhythmic drugs in vivo and in vitro.

PMID- 14593372
TI  - [Endothelin receptor blockers--one more agent for the treatment of pulmonary
      hypertension].
AB  - Data on participation of derangements of pulmonary vessel endothelial function in
      pathogenesis of pulmonary hypertension served as basis for therapeutic use of
      prostanoids, sildenafil, and endothelin(ET) receptor blockers. A first
      representative of the latter group - bosentan (nonselective ET-receptor
      antagonist) has been recently registered as an agent for the treatment of
      pulmonary hypertension. Bosentan and other ET receptor antagonists has been
      studied in several trials. Results of these trials are reviewed in this paper
      which also contains characteristics of main representatives of ET receptor
      antagonists as well as information on their tolerability and major side effects.

PMID- 14593373
TI  - [Significance of the system of atrial natriuretic peptides in heart failure and
      hypertension].
AB  - This literature review presents current information on mechanisms of realization
      and action of natriuretic peptides in heart failure and hypertension. Significant
      role in degradation of natriuretic peptides belongs to neutral endopeptidase.
      Basing on theoretical and experimental data novel class of drugs - inhibitors of
      neutral endopeptidase - has been developed. The paper contains discussion of
      first results of the use of drugs from this class for the treatment of chronic
      heart failure.

PMID- 14593375
TI  - [Current trends of cardiovascular morbidity and mortality of children in Russian
      Federation. Structure of cardiac pathology in childhood].
AB  - Analysis of structure and prevalences of cardiovascular diseases among children
      and adolescents is presented and recent trends of cardiovascular morbidity and
      mortality as well as regional differences in dynamics of these parameters in this
      age group are discussed. Current situation is characterized by pronounced
      lowering of age of onset of cardiovascular diseases previously considered as
      diseases of the adult. Clinical picture and prognosis of many pathological states
      also has been changed. Since the beginning of the nineties steep rise (more than
      2 fold) of morbidity and total number of children with cardiovascular pathology
      has occurred. This is directly linked with improved diagnostics. While all cause
      and infant mortality becomes lower cardiovascular mortality remains stable and
      even has tendency to increase. Mortality from cardiac and vascular diseases is
      significantly lower in regions with higher prevalence of these states.
      Substantial effect on lowering of mortality produces intensity of work of
      specialized services providing timely diagnosis, treatment and rehabilitation of
      children with heart diseases. The authors suggest some parameters allowing to
      assess progressive or negative trends in development of specialized care of
      children with cardiovascular pathology.

PMID- 14593374
TI  - [Metoprolol CR/XL: advanced formulation of a classical beta-blocker].
AB  - Metoprolol is a selective beta(1)-adrenergic antagonist extensively used in major
      fields of cardiology since 1975. Metoprolol has proven its efficacy in reducing
      cardiovascular events and mortality in patients with hypertension and coronary
      heart disease in large clinical trials. Recently developed controlled
      release/extended release (CR/XL) formulation of metoprolol succinate was designed
      to provide relatively constant metoprolol plasma concentrations and beta(1)
      blockade while retaining the convenience of once daily administration. The
      avoidance of high peak plasma concentrations with metoprolol succinate is
      associated with lesser degree of adverse effects and may improve patients
      compliance. This formulation of metoprolol has demonstrated efficacy in reducing
      cardiovascular events and mortality in patients with heart failure. More recently
      evidence for antiatherogenic activity of metoprolol succinate has been also
      obtained.

PMID- 14593376
TI  - [Rheolytic thrombectomy with AngioJet catheter during transluminal coronary
      revascularization in patients with acute myocardial infarction].
AB  - BACKGROUND: Although balloon angioplasty and stenting are effective in the
      treatment of acute myocardial infarction (M1), reduced coronary flow and distal
      embolization frequently complicate interventions when thrombus is present.
      Adjunctive treatment with mechanical thrombectomy devices was suggested to reduce
      these complications. METHODS: We evaluated immediate angiographic, in-hospital
      and 30-day follow-up clinical outcomes of 185 patients with acute MI and
      angiographically evident thrombus who were treated with AngioJet rheolytic
      thrombectomy followed by immediate definitive treatment. RESULTS: Procedural
      success (residual diameter stenosis <50% and thrombolysis in myocardial
      infarction [TIMI] flow >2 after final treatment) was 97%. Rheolytic thrombectomy
      success was achieved in 7% of patients. Subsequent definitive treatment included
      stenting in 67% and balloon angioplasty alone in 26% of patients. Final TIMI 3
      flow was achieved in 89%. AngioJet treatment resulted in mean thrombus area
      reduction from 69.6 mm(2) at baseline to 17.3 mm(2) post-thrombectomy (p<0.001).
      Procedural complications included distal embolization (7.6%) and perforation
      (1.1%). Clinical success (procedure success without major in-hospital cardiac
      events) rate was 88%, in-hospital mortality - 7.0%. There were no further major
      adverse events during 30-day follow-up. CONCLUSION: Rheolytic thrombectomy can be
      performed safely and effectively in patients with acute MI, allowing for
      immediate definitive treatment of thrombus-containing lesions.

PMID- 14593377
TI  - [A novel approach to assessment of individual 24-hour heart rate variability].
AB  - A novel approach to assessment of individual 24-hour heart rate variability (HRV)
      has been suggested. This approach allows to compare sequences of RR intervals
      with knowingly nonstationary rhythm and to obtain valuable information on
      direction (increase or decrease) of HRV changes. The latter was not achievable by
      existing techniques. Main feature of the novel approach is consideration of
      dependence of sinus arrhythmia on heart rate on a given time interval
      (rhythmogram fragment). This became possible due to use of implementation of a
      new characteristic of 24-hour HRV - mean weighted variation of rhythmogram
      (MWVR). This parameter repesented a generalization of a previously introduced
      variation of short rhythmogram fragment (VSRF) and was formed in the following
      way. Rhythmogram was divided into short fragments and within each fragment VSRF
      was calculated. Then average variations were averaged for different ranges of HR
      changes. Each averaged variation was multiplied by weight coefficient which
      depended on corresponding range of HR changes, and by portion (expressed in
      percent) of overall number of short rhythmogram fragments belonging to this
      range. MWVR was determined as sum of resulting multiples. Analysis of
      rhythmograms from 58 healthy persons showed that MWVR declined with age. In
      patients with heart failure (n=80) mean MWVR was lower than in healthy persons
      and decreased with increase of NYHA class of heart failure. Eight patients were
      restudied while they were classified to a different heart failure class.
      Transition to a higher class was associated with lowering of MWVR and vice versa.
      Thus MWVR adequately reflected dynamics of functional state of an individual
      patient.

PMID- 14593378
TI  - [Dynamics of parameters of variability of processes of repolarization after
      transluminal balloon angioplasty in patients with ischemic heart disease].
AB  - AIM: To study dynamics of processes of repolarization after transluminal balloon
      angioplasty in patients with ischemic heart disease. MATERIAL AND METHODS: ECG,
      Holter ECG monitoring, analysis of parameters of variability of processes of
      repolarization, echocardiography and treadmill stress echocardiography were
      carried out in 28 ischemic heart disease patients aged 51.3+/-8.1 years prior to
      percutaneous coronary intervention, before discharge and in 4.1+/-2.1 months
      after procedure. Coronary angiography was repeated after intervention when
      restenosis was suspected because of positive stress echo. RESULTS: Number of
      vessels with significant stenoses was 1.8+/-0.1, number of implanted stents -
      2.0+/-0.2. Analysis of parameters of variability of processes of repolarization
      at rest and after exercise revealed significant increases of maximal value of QT
      (MQT(c)) and of its dispersion (QT(cd)). In 3-5 days after procedure significant
      lowering of these parameters occurred. Development of restenosis during follow-up
      (in 6 patients, 21.4%) was associated with repeated increases of MQT(c) and
      QT(cd). CONCLUSION: MQT(c) and QT(cd) are sensitive to myocardial ischemia and
      can be used as supplementary markers of myocardial ischemia during exercise tests
      in patients with ischemic heart disease.

PMID- 14593379
TI  - [Parameters of heart rate variability during bicycle ergometry test].
AB  - Short-term (5 min) heart rate variability (HRV) was studied before and during
      submaximal bicycle exercise tests in 27 patients with ischemic heart disease, 23
      patients with hypertension and 9 healthy subjects. Low-frequency (0.04 to 0.15
      Hz) and high-frequency (0.15 to 0.40 Hz) power components of HRV were
      significantly decreased during submaximal exercise. The level of load at which
      abrupt decrease of low-frequency components below 40 ms(2) occurred possibly
      reflected individual exercise tolerance. Episodes of myocardial ischemia were
      associated with pronounced decreases of low - frequency HRV components.

PMID- 14593380
TI  - [Clinical efficacy of myocardial cytoprotector trimetazidine in peri- and
      postmenopausal women with ischemic heart disease].
AB  - Efficacy of 3-12 month use of trimetazidine hydrochloride combined with verapamil
      was assessed in postmenopausal women with effort angina by repetitive exercise
      tests, ECG monitoring and echocardiography. The use of trimetazidine was
      associated with augmentation of antianginal and antiischemic action of verapamil,
      improvement of systolic and diastolic left ventricular function, decrease in
      frequency of hospitalizations because of exacerbation of ischemic heart disease.
      These effects were evident in all age groups throughout the period of observation
      and did not depend on the ischemic heart disease duration.

PMID- 14593381
TI  - [Atorvastatin in the treatment of patients with hereditary hypercholesterolemia].
AB  - Efficacy and tolerability of atorvastatin (20 mg/day) were assessed in a 3 month
      study on 19 patients (5 men, 14 women, mean age 52.3 years) with familial
      hypercholesterolemia. Average baseline levels of total cholesterol (CH) and low
      density lipoprotein (LDL) CH were 10.7 and 8.6 mmol/l, respectively. By the end
      of 3 months levels of CH, LDL CH, triglycerides and atherogeneity index decreased
      by 32, 41, 16 and 45%, respectively. This was accompanied by 21% increase of high
      density lipoprotein CH level. There were no cases of AST or ALT activity
      elevation above 3 upper limits of normal values. However 1 patient had
      asymptomatic elevation of ALT activity up to 53 U/l which did not cause
      interruption of therapy. Creatine kinase remained normal throughout the study
      period. Three patients (16%) stopped taking atorvastatin because of side effects.
      Thus in patients with familial hypercholesterolemia the dose of atorvastatin 20
      mg/day was sufficiently well tolerated and provided effective control of lipid
      levels.

PMID- 14593382
TI  - [Atherosclerosis of abdominal aorta and carotid arteries and its correlation with
      blood serum lipid levels in cholelithiasis].
AB  - AIM: To elucidate relationship between cholelithiasis and presence and severity
      of atherosclerosis in abdominal aorta and carotid arteries. MATERIAL AND METHODS:
      Ultrasound investigation of vessels and abdominal organs, determination of blood
      serum total, high density lipoprotein cholesterol and triglycerides were carried
      out in 147 patients with and 167 without (controls) cholelithiasis (mean age
      44.2+/-3.1 and 45+/-2.8 years, respectively). RESULTS: Among patients with
      cholelithiasis 73.2 and 67.6% had atherosclerosis of abdominal aorta and carotid
      arteries, respectively. This was significantly more than in controls. Compared
      with controls atherosclerosis of these vessels in all age groups was
      significantly more pronounced in patients with cholelithiasis. Moreover severity
      of atherosclerosis was directly related to duration and activity of
      cholelithiasis. Atherosclerosis of abdominal aorta and carotids was most
      pronounced in patients with cholelithiasis and concomitant hypertension, ischemic
      heart disease and obesity. Significant direct correlations were found between
      blood serum levels of total cholesterol, triglycerides and low density
      lipoprotein cholesterol and thickness of abdominal aortic wall and carotid artery
      intima media complex. CONCLUSION: The results evidence for the existence of
      association between cholelithiasis and presence and severity of atherosclerosis
      of abdominal aorta and carotid arteries.

PMID- 14593384
TI  - [Evaluation of cerebral hemodynamics in patients with syndrome of obstructive
      sleep apnea by long term registration of rheoencephalogram].
AB  - AIM: To assess cerebral hemodynamics during sleep in patients with syndrome of
      obstructive sleep apnea. METHODS: Long term monitoring of rheoencephalogram. Data
      processing consisted in construction of trends (curves of changes of
      rheographical parameters during any selected time interval). RESULTS AND
      CONCLUSION: Cyclical periods of apnea are associated with negative changes of
      cerebral hemodynamics. At the end of period of apnea despite compensatory
      vasodilatation cerebral blood flow decreases. This occurs during pronounced
      hypoxemia and can predispose to ischemic disturbances. In ventilation phase rapid
      rise of heart rate and blood pressure at the background of continuing cerebral
      vasodilatation can increase risk of hemorrhagic complications.

PMID- 14593383
TI  - [Longitudinal global and regional left ventricular function in patients with
      hypertensive disease (tissue Doppler echocardiography data)].
AB  - Impulse tissue doppler study was carried out in 154 patients with hypertensive
      disease (age 35-60 years) and 39 practically healthy volunteers (mean age 43.4+/
      5.5 years). According to left ventricular geometry the following groups of
      patients were distinguished (after A.Ganau): with normal geometry (n=47), with
      concentric remodeling (n=12), with concentric hypertrophy (n=53), and with
      eccentric hypertrophy (n=42). Tissue doppler spectrum was registered from mitral
      annulus and 15 left ventricular segments. The following characteristics were
      obtained: in each annular spectrum - maximal velocities of peaks s(m), e(m),
      a(m), ratio e(m)/a(m), isovolumic relaxation time (ivrt) and their average values
      (from 6 measurements); in each left ventricular segmental spectrum - maximal
      velocities of waves s, e, a, ratio e/a and segmental ivrt. Compared with healthy
      persons patients with hypertension had lowered longitudinal global systolic
      function of the left ventricle. Patients with concentric left ventricular
      hypertrophy had least values of e(m), e(m)/a(m), ivrt(m) and greatest number of
      dysfunctional (e/a<1.0 and ivrt>90 ms) segments. Some hypertensive patients with
      normal values of transmitral blood flow had signs of segmental diastolic
      dysfunction. Among patients with normal left ventricular geometry isolated
      segmental diastolic dysfunction was revealed according to e/a in 12 of 20 (60%),
      according to ivrt in 11 of 22 (50%). All patients with concentric and eccentric
      left ventricular hypertrophy had segmental diastolic dysfunction. Thus impulse
      tissue doppler study is indicated to patients with hypertension and normal
      parameters of transmitral flow for assessment of longitudinal segmental diastolic
      left ventricular function.

PMID- 14593385
TI  - [Tissue plasminogen activator and plasminogen activator inhibitor gene
      polymorphisms: possible relation to atherosclerosis and its complications].
AB  - In the present review the dates about association of genetic variants of a
      plasminogen activator inhibitor type 1 (PAI-1) and tissue plasminogen activator
      (tPA) with ischemic heart disease and atherosclerosis of other localization are
      toted. The singularities of synthesis of PAI-1 and tPA, possible paths of
      regulation of their activity briefly surveyed. Known polymorphisms of PAI-1 gene
      and tPA gene, their localization, frequencies in different ethnic groups are
      circumscribed. In operation the genetic influence of polymorphisms of PAI-1 gene
      and tPA gene on synthesis and plasma concentration of PAI-1 and tPA, including
      under an operation of risk factors of atherosclerosis, and as possible clinical
      consequences of sectional violations is featured. In the review the possible role
      of polymorphisms of PAI-1 gene and tPA gene in a pathogenesis of atherosclerosis,
      association with hazard thrombotic complications for different diseases is
      considered. Many clinical examinations are circumscribed which have confirmed or
      not confirmed a possible connection of genetic markers with development and
      current of ischemic heart disease and other vascular diseases. We considered that
      there are no enough dates to one valued estimation of possible role of
      polymorphisms of PAI-1 and tPA genes in pathogenesis of atherosclerosis. It is
      necessary to get new genetic studies in groups of patient with high risk of
      ischemic heart disease and atherosclerosis.

PMID- 14593386
TI  - Let there be light!

PMID- 14593390
TI  - Lithium batteries: a spectacularly reactive cathode.

PMID- 14593388
TI  - On the electronic conductivity of phospho-olivines as lithium storage electrodes.

PMID- 14593391
TI  - Spin electronics: a quantum leap.

PMID- 14593392
TI  - Drug delivery: pulsed polymers.

PMID- 14593393
TI  - Supramolecular chemistry: fluorine makes a difference.

PMID- 14593394
TI  - Nanoscale science: complex rules for soft systems.

PMID- 14593396
TI  - Cell and molecular mechanics of biological materials.
AB  - Living cells can sense mechanical forces and convert them into biological
      responses. Similarly, biological and biochemical signals are known to influence
      the abilities of cells to sense, generate and bear mechanical forces. Studies
      into the mechanics of single cells, subcellular components and biological
      molecules have rapidly evolved during the past decade with significant
      implications for biotechnology and human health. This progress has been
      facilitated by new capabilities for measuring forces and displacements with
      piconewton and nanometre resolutions, respectively, and by improvements in bio
      imaging. Details of mechanical, chemical and biological interactions in cells
      remain elusive. However, the mechanical deformation of proteins and nucleic acids
      may provide key insights for understanding the changes in cellular structure,
      response and function under force, and offer new opportunities for the diagnosis
      and treatment of disease. This review discusses some basic features of the
      deformation of single cells and biomolecules, and examines opportunities for
      further research.

PMID- 14593397
TI  - A high-wire act.

PMID- 14593398
TI  - PDGFRB is overexpressed in metastatic medulloblastoma.

PMID- 14593400
TI  - The comings and goings of a Y polymorphism.

PMID- 14593401
TI  - A keaper and a striker maintain epidermal homeostasis.

PMID- 14593402
TI  - Lethal combinations.

PMID- 14593407
TI  - Maintenance of heterochromatin by RNA interference of tandem repeats.
AB  - Tandem repeats are prone to epigenetic silencing regulated by RNA interference.
      This may be because siRNAs from tandem array transcripts are regenerated by RNA
      dependent RNA polymerase (RdRP) and Dicer, but siRNAs from single-copy sequences
      are exhausted by sequential use of downstream primers by RdRP. This could account
      for the formation of heterochromatin from tandem repeats.

PMID- 14593403
TI  - Vibrating in the background.

PMID- 14593410
TI  - NCB demography--democracy?

PMID- 14593411
TI  - The case for morphogens in plants.
AB  - Plants and animals have evolved as multicellular organisms independently of one
      another. This raises the intriguing question of whether plants and animals have
      developed similar or distinct patterning strategies to establish their body
      plans. Animals use concentration gradients of signals termed morphogens for
      tissue patterning, but whether they are also used by plants is unclear. Here we
      compare and contrast the plant hormone auxin with animal morphogens, and
      speculate as to whether plants have independently evolved similar mechanisms to
      regulate pattern formation.

PMID- 14593413
TI  - The kinetochore NUPtials.

PMID- 14593414
TI  - Architects of the chromosome.

PMID- 14593415
TI  - Stuck without Traffic Jam.

PMID- 14593416
TI  - BTB proteins as henchmen of Cul3-based ubiquitin ligases.

PMID- 14593417
TI  - Stem cell fusion in the brain.

PMID- 14593418
TI  - Plant microtubule nucleation sites: moving right along.

PMID- 14593419
TI  - Three Yips for Rab recruitment.

PMID- 14593420
TI  - Cell of the month: An insect blood cell engulfing bacteria.

PMID- 14593424
TI  - Sequence? What Sequence?: the human medial temporal lobe and sequence learning.

PMID- 14593421
TI  - Homologue disjunction in mouse oocytes requires proteolysis of securin and cyclin
      B1.
AB  - Disjunction of pairs of homologous chromosomes during the first meiotic division
      (MI) requires anaphase-promoting complex (APC)-mediated activation of separase in
      budding yeast and Caenorhabditis elegans, but not Xenopus laevis. It is not clear
      which model best fits the mammalian system. Here we show that homologue
      disjunction in mouse oocytes is dependent on proteolysis of the separase
      inhibitor securin and the Cdk1 regulatory sub-unit cyclin B1. Proteolysis of both
      proteins was entirely dependent on their conserved destruction box (D-box)
      motifs, through which they are targeted to the APC. These data indicate that the
      mechanisms regulating homologue disjunction in mammalian oocytes are similar to
      those of budding yeast and C.elegans.

PMID- 14593425
TI  - BDNF gene expression is reduced in the frontal cortex of dopamine transporter
      knockout mice.

PMID- 14593426
TI  - Association of the serotonin transporter promoter polymorphism with suicidal
      behavior.

PMID- 14593427
TI  - Polymorphisms in the 5'-untranslated region of the human serotonin receptor 1B
      (HTR1B) gene affect gene expression.
AB  - We present evidence of complex balancing regulation of HTR1B transcription by
      common polymorphisms in its promoter. Computational analysis of the HTR1B gene
      predicted that a 5' segment, spanning common DNA sequence variations, T-261G, A
      161T, and -182INS/DEL-181, contained a putative functional promoter. Using a
      secreted alkaline phosphatase (SEAP) reporter gene system, we found that the
      haplotype -261G_-182INS-181_A-161 enhanced transcriptional activity 2.3-fold
      compared with the haplotype T-261_-182INS-181_A-161. Conversely, -161T reversed
      this, and the net effect when -261G and -161T were in the same haplotype (-261G_
      182INS-181_-161T) was equivalent to the major haplotype (T-261_-182INS-181_A
      161). Electrophoretic mobility shift experiments showed that -261G and -161T
      modify the binding of transcription factors (TFs): -261G generates a new AP2
      binding site, while alleles A-161 and -161T exhibit different binding
      characteristics to AP1. T-261G and A-161T were found to be in linkage
      disequilibrium (LD) with G861C in a European ancestry population. Interestingly,
      G861C has been reported to be associated with several psychiatric disorders. Our
      results indicate that HTR1B is the target of substantial transcriptional genetic
      regulation by common haplotypes, which are in LD with the HTR1B single-nucleotide
      polymorphism (SNP) most commonly used in association studies.

PMID- 14593428
TI  - Meta-analysis identifies an association between the dopamine D2 receptor gene and
      schizophrenia.
AB  - The D2 subtype of dopamine receptor has been widely implicated in the
      pathogenesis of schizophrenia. Early evidence supporting an association between
      the Cys311Ser polymorphism of the D2 receptor gene (DRD2) and schizophrenia was
      subsequently refuted and, eventually, dismissed. From all 24 published case
      control studies, we calculated a pooled estimate of this association. The pooled
      odds ratio was 1.3 for the Cys allele, which was highly significant (P=0.007).
      The odds ratio derived from each study was unrelated to the ethnicity or gender
      composition of the sample, or the age of the control group. There was no evidence
      of publication bias or excessive influence attributable to any given study.
      Although more family-based studies are needed to confirm this relation, our
      results provide strong evidence that DRD2 influences susceptibility to
      schizophrenia.

PMID- 14593429
TI  - Screening of nine candidate genes for autism on chromosome 2q reveals rare
      nonsynonymous variants in the cAMP-GEFII gene.
AB  - The results from several genome scans indicate that chromosome 2q21-q33 is likely
      to contain an autism susceptibility locus. We studied the potential contribution
      of nine positional and functional candidate genes: TBR-1; GAD1; DLX1; DLX2; cAMP
      GEFII; CHN1; ATF2; HOXD1 and NEUROD1. Screening these genes for DNA variants and
      association analysis using intragenic single nucleotide polymorphisms did not
      provide evidence for a major role in the aetiology of autism. Four rare
      nonsynonymous variants were identified, however, in the cAMP-GEFII gene. These
      variants were present in five families, where they segregate with the autistic
      phenotype, and were not observed in control individuals. The significance of
      these variants is unclear, as their low frequency in IMGSAC families does not
      account for the relatively strong linkage signal at the 2q locus. Further studies
      are needed to clarify the contribution of cAMP-GEFII gene variants to autism
      susceptibility.

PMID- 14593431
TI  - Serotonin transporter missense mutation associated with a complex
      neuropsychiatric phenotype.
AB  - Two common serotonin transporter (SERT) untranslated region gene variants have
      been intensively studied, but remain inconclusively linked to depression and
      other neuropsychiatric disorders. We now report an uncommon coding region SERT
      mutation, Ile425Val, in two unrelated families with OCD and other serotonin
      related disorders. Six of the seven family members with this mutation had OCD
      (n=5) or obsessive-compulsive personality disorder (n=1) and some also met
      diagnostic criteria for multiple other disorders (Asperger's syndrome, social
      phobia, anorexia nervosa, tic disorder and alcohol and other substance
      abuse/dependence). The four most clinically affected individuals--the two
      probands and their two slbs--had the I425V SERT gene gain-of-function mutation
      and were also homozygous for 5'-UTR SERT gene variant with greater
      transcriptional efficacy.

PMID- 14593430
TI  - Selectively bred Wistar-Kyoto rats: an animal model of depression and hyper
      responsiveness to antidepressants.
AB  - The Wistar-Kyoto (WKY) rat strain demonstrates endogenous hormonal and behavioral
      abnormalities that emulate many of those found in symptom-presenting depressive
      patients. Evidence suggests that the WKY strain may harbor heterogeneity not
      found in other inbred strains, including greater behavioral and genetic
      variability. We took advantage of this variability and selectively bred WKY for
      'depressive' behavior using immobility in the forced swim test (FST) as a
      functional selector. Successive generations of selective breeding resulted in
      rats that exhibited the extremes of immobility in the FST: 'WKY most immobile'
      (WMI) and 'WKY least immobile' (WLI). Male WMI rats also showed significantly
      decreased activity in the open field test (OFT). Plasma corticosterone (CORT)
      response to restraint stress was significantly lower and less variable in WMI
      compared to WLI males. Subacute treatment of males with several classes of
      antidepressant had different effects on FST behavior in the two substrains. Both
      desipramine (10 mg/kg body weight), a tricyclic antidepressant, and phenelzine
      (7.5 mg/kg), a monoamine oxidase inhibitor, significantly and drastically
      decreased FST immobility in WMI. In contrast, WLI showed a limited response to
      these antidepressants. Neither substrain responded to fluoxetine (10 mg/kg), a
      selective serotonin reuptake inhibitor. These data show that selective breeding
      of WKY rats has resulted in two substrains with reduced variability and differing
      responsiveness to antidepressants, which represent a novel means to dissect the
      molecular mechanisms underlying depressive behavior.

PMID- 14593432
TI  - M129V variation in the prion protein may influence cognitive performance.
AB  - Correlations between general intelligence (g) and brain volume are about 0.40,
      and the correlation between g and white matter volume has been reported to be
      largely due to genetic factors. Establishing that the correlation between brain
      volumes and cognitive abilities is mediated by shared genetic factors is only the
      first step in unveiling the relation between them. We have recently shown that
      methionine at codon 129 in the prion protein is associated with white matter
      reduction in a group of healthy volunteers and schizophrenic patients. The
      present study examines the influence of the same genetic variation on
      psychometric cognitive performance measurements in 335 community-based healthy
      volunteers. The polymorphism was associated with Full Scale IQ (genotype: F=4.38,
      df=2/317, P=0.013; allele: F=8.04, df=1/658, P=0.005), as measured by HAWIE-R
      (German version of the Wechsler Adult Intelligence Scale, Revised). Genotype
      accounted for 2.7% of the total variability in Full Scale IQ (partial
      eta2=0.027). An exploratory analysis revealed association with several HAWIE-R
      subscales; the association with the Digit Symbol subtest remained significant
      after correction for multiple testing. In summary, we deliver evidence for an
      association of a common genetic variation in the prion protein gene with
      cognitive performance. However, independent replications are needed before firm
      conclusions can be drawn.

PMID- 14593433
TI  - A polymorphism (5-HTTLPR) in the serotonin transporter promoter gene is
      associated with DSM-IV depression subtypes in seasonal affective disorder.
AB  - Serotonergic mechanisms are thought to play an important role in the pathogenesis
      of seasonal affective disorder (SAD). The expression of the serotonin transporter
      (5-HTT) is regulated in part by an insertion/deletion polymorphism in the
      serotonin transporter gene promoter region (5-HTTLPR). The 5-HTTLPR short allele
      (s) has been associated with anxiety-related personality traits and depression,
      and one study observed an association between the 5-HTTLPR s-allele and SAD and
      the trait of seasonality. We genotyped 138 SAD patients and 146 healthy
      volunteers with low seasonality for 5-HTTLPR. No difference between patients and
      controls was found for genotype distribution and s-allele frequency. However,
      genotype distribution and allele frequencies were strongly associated with DSM-IV
      depression subtypes. Melancholic depression was associated with the 5-HTTLPR long
      (l) allele and atypical depression with the 5-HTTLPR s-allele (two-sided Fisher's
      exact test: genotype distribution: P=0.0038; allele frequencies: P=0.007). Our
      data are compatible with the hypothesis of a disease process that is not causally
      related to 5-HTTLPR, but involves 5-HT neurotransmission and 5-HTTLPR somewhere
      on its way to phenotypic disease expression.

PMID- 14593435
TI  - Nano-nonsense.

PMID- 14593436
TI  - Medicine on a small scale.

PMID- 14593437
TI  - The hazards of space travel.

PMID- 14593438
TI  - Building healthy families.

PMID- 14593439
TI  - Pioneers in medicine.

PMID- 14593440
TI  - Analyse this.

PMID- 14593443
TI  - RNA sensors: novel regulators of gene expression.
AB  - RNA-mediated control can evolve far more rapidly than mechanisms that rely on
      proteins, creating selective advantages in adaptive gene regulation. Recently,
      evidence has emerged that messenger RNA is a source of cis-acting RNA elements
      that sense external signals and thereby regulate gene expression. With exquisite
      specificity, metabolite-sensing riboswitches control the formation or translation
      of prokaryotic mRNA. In eukaryotes, RNA sensors in human antiviral cytokine genes
      that encode tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN
      gamma) have been shown to activate strongly the RNA-dependent protein kinase PKR,
      a stress kinase that is also activated by double-stranded RNA--a hallmark of
      viral infection. These cis-acting RNA elements in the TNF-alpha and IFN-gamma
      transcripts function as sensors of intracellular PKR levels and regulate gene
      expression at the level of mRNA splicing and translation, respectively. Although
      RNA sensors in bacteria may be remnants of an ancient RNA world, it is likely
      that they form an integral part of higher eukaryotic genomes as well.

PMID- 14593442
TI  - Potassium channel regulation.
AB  - The sulphonylurea receptor (SUR) is a member of the ATP-binding cassette (ABC)
      family of membrane proteins. It functions as the regulatory subunit of the ATP
      sensitive potassium (KATP) channel, which comprises SUR and Kir6.x proteins.
      Here, we review data demonstrating functional differences between the two
      nucleotide binding domains (NBDs) of SUR1. In addition, to explain the structural
      basis of these functional differences, we have constructed a molecular model of
      the NBD dimer of human SUR1. We discuss the experimental data in the context of
      this model, and show how the model can be used to design experiments aimed at
      elucidating the relationship between the structure and function of the KATP
      channel.

PMID- 14593445
TI  - Magnetic resonance imaging of carotid artery abnormalities in patients with
      sphenoid sinusitis.
AB  - Sphenoid sinusitis is unusual in children, but when it occurs, it can lead to
      serious intracranial complications. We show the value of MRI in demonstrating
      intracranial abnormalities due to sphenoid sinus infection, particularly those
      involving the internal carotid arteries and cavernous sinuses. We reviewed our
      imaging experience of sphenoid sinusitis and found four patients with ICA
      narrowing who had undergone MR evaluation including conventional and diffusion
      imaging. MR angiography was also performed in three patients to determine the
      extent of ICA narrowing. Narrowing of ICA was found in the cavernous segment in
      all patients and in the supraclinoid segment in three. Cerebral infarction was
      found in two patients. In one patient the cavernous sinus showed hyperintensity
      on diffusion-weighted images and hypointensity on apparent diffusion coefficient
      map, suggesting reduced diffusion. Although infrequent in children, sphenoid
      sinus infection should be considered as a possible cause of intracranial
      infection, particularly in teenagers. Early recognition of cavernous sinus
      involvement and ICA narrowing may lead to prompt treatment and hence a more
      favorable outcome.

PMID- 14593444
TI  - Proton MRS in Behcet's disease with and without neurological findings.
AB  - Our aim was to investigate whether neurological impairment in Behcet's disease
      (BD) can be assessed by means of proton MRS and whether it can assist in
      prognosis. We used single-voxel MRS to measure metabolites in regions of normal
      appearing pons, basal ganglia and periventricular white matter (PWM) in 32
      patients with chronic BD patients with and without neurological deficits and 29
      control subjects. Patients had significantly higher N-acetylaspartate
      (NAA)/creatine (Cr) and choline (Cho)/Cr ratios in the basal ganglia than the
      controls. The Cho/Cr ratio in the PWM was also significantly higher in the
      patients. MRS enabled clear discrimination of patients and controls and also
      revealed spectral differences between non-neuro-Behcet's disease and neuro
      Behcet's disease in the basal ganglia. MRS can be used to assess brain
      involvement in BD even if structural changes are absent.

PMID- 14593446
TI  - Progressive multifocal leukoencephalopathy: diffusion-weighted imaging and
      pathological correlations.
AB  - We examined MRI of two patients with progressive multifocal leukoencephalopathy
      (PML), including diffusion-weighted imaging (DWI), with calculation of apparent
      diffusion coefficients (ADC). The pathology findings of one patient were compared
      with those of MRI. The lesions had different ADC and DWI appearances, depending
      on the stage of the disease. Newer lesions and the advancing edge of large
      lesions had normal-to-low ADC and gave high signal on DWI. Older lesions and the
      centre of large lesions had increased ADC and gave low signal. High signal on DWI
      and low ADC mark the regions of active infection and cell swelling,
      distinguishing them from areas of reparative gliosis.

PMID- 14593447
TI  - Chemical identification of N-acyl homoserine lactone quorum-sensing signals
      produced by Sinorhizobium meliloti strains in defined medium.
AB  - The N-acyl homoserine lactone (AHL) quorum-sensing signals produced by
      Sinorhizobium meliloti strains AK631 and 1021 when cultured in a defined glucose
      nitrate medium were identified by gas chromatography/mass spectrometry (GC/MS)
      and electrospray ionization tandem mass spectrometry (ESI MS/MS). Both strains
      synthesized several long-chain AHLs. Defined medium cultures of strain AK631
      synthesized a complex mixture of AHLs with short acyl side chains. Strain 1021
      produced no short-chain AHLs when grown on defined medium and made a somewhat
      different set of long-chain AHLs than previously reported for cultures in rich
      medium. While the two strains produced several AHLs in common, the differences in
      AHLs produced suggest that there may be significant differences in their patterns
      of quorum-sensing regulation.

PMID- 14593448
TI  - Identification of the 7,8-didemethyl-8-hydroxy-5-deazariboflavin synthase
      required for coenzyme F(420) biosynthesis.
AB  - The hydride carrier coenzyme F(420) contains the unusual chromophore 7,8
      didemethyl-8-hydroxy-5-deazariboflavin (FO). Microbes that generate F(420)
      produce this FO moiety using a pyrimidine intermediate from riboflavin
      biosynthesis and the 4-hydroxyphenylpyruvate precursor of tyrosine. The fbiC
      gene, cloned from Mycobacterium smegmatis, encodes the bifunctional FO synthase.
      Expression of this protein in Escherichia coli caused the host cells to produce
      FO during growth, and activated cell-free extracts catalyze FO biosynthesis in
      vitro. FO synthase in the methanogenic euryarchaeon Methanocaldococcus jannaschii
      comprises two proteins encoded by cofG (MJ0446) and cofH (MJ1431). Both subunits
      were required for FO biosynthesis in vivo and in vitro. Cyanobacterial genomes
      encode homologs of both genes, which are used to produce the coenzyme for FO
      dependent DNA photolyases. A molecular phylogeny of the paralogous cofG and cofH
      genes is consistent with the genes being vertically inherited within the
      euryarchaeal, cyanobacterial, and actinomycetal lineages. Ancestors of the
      cyanobacteria and actinomycetes must have acquired the two genes, which
      subsequently fused in actinomycetes. Both CofG and CofH have putative radical S
      adenosylmethionine binding motifs, and pre-incubation with S-adenosylmethionine,
      Fe(2+), sulfide, and dithionite stimulates FO production. Therefore a radical
      reaction mechanism is proposed for the biosynthesis of FO.

PMID- 14593449
TI  - Type IV pili-related natural transformation systems: DNA transport in mesophilic
      and thermophilic bacteria.
AB  - Horizontal gene flow is a driving force for bacterial adaptation. Among the three
      distinct mechanisms of gene transfer in bacteria, conjugation, transduction, and
      transformation, the latter, which includes competence induction, DNA binding, and
      DNA uptake, is perhaps the most versatile mechanism and allows the incorporation
      of free DNA from diverse bacterial species. Here we review DNA transport
      machineries mediating uptake of naked DNA in gram-positive and gram-negative
      bacteria. Different putative models of transformation machineries comprising
      components similar to proteins of type IV pili are presented. Emphasis is placed
      on a comparative discussion of the underlying mechanisms of DNA transfer in
      mesophilic and extremely thermophilic bacteria, highlighting conserved and
      distinctive features of these transformation machineries.

PMID- 14593450
TI  - The risk and burden of vertebral fractures in Sweden.
AB  - The aim of this study was to determine the risk and burden of vertebral fractures
      judged as those coming to clinical attention and as morphometric fractures.
      Incidence and utility loss were computed from data from Malmo, Sweden. Clinical
      fractures accounted for 23% of all vertebral deformities in women and for 42% in
      men. The average 10-year fracture probability for morphometric fractures
      increased with age in men from 2.9% at the age of 50 years (7.2% in women) to 8.4
      at the age of 85 years (26.7% in women). As expected, probabilities increased
      with decreasing T-score for hip BMD. Cumulative utility loss from a clinical
      vertebral fracture was substantial and was 50-62% of that due to a hip fracture
      depending on age. When incidence of fractures in the population was weighted by
      disutility, all spine fractures accounted for more morbidity than hip fracture up
      to the age of 75 years. We conclude that vertebral fractures have a major
      personal and societal impact that needs to be recognised in algorithms for
      assessment of risk and in health economic strategies for osteoporosis.

PMID- 14593451
TI  - Mortality after osteoporotic fractures.
AB  - The aim of this study was to examine the pattern of mortality following
      osteoporotic fractures at the spine, shoulder, hip, and forearm. We studied 2,847
      patients with fractures at these sites identified from the radiology department
      in Malmo, Sweden. Poisson regression was used to compute mortality immediately
      after the fracture and with time. Mortality immediately after fracture was
      significantly higher in fracture cases than in the general population except for
      forearm fractures in both men and women. Mortality was higher in men than in
      women, but not different when adjusted for sex-specific population risks. For
      spine, shoulder, and hip fracture, mortality fell after the 1st year, an effect
      that was most marked for patients with spine fractures. The decrease in mortality
      risk with time was significant for hip, vertebral, and shoulder fracture. We
      conclude that the risk of death is increased in patients with osteoporotic
      fractures and that the highest risk is found immediately after the fracture
      event. The decreasing mortality with time after fracture may be due in part to a
      decrease in deaths causally related to the fracture. The extent to which early
      intervention for osteoporosis might avoid some of these deaths is unknown.

PMID- 14593452
TI  - Adherence with hip protectors: a proposal for standardised definitions.
AB  - Definitions of adherence, also termed compliance, with use of hip protectors have
      varied in published studies, making interpretation of results difficult. This
      paper proposes standard definitions of adherence with the use of hip protectors.
      Adherence is the wearing of hip protectors in accordance with the recommendations
      of the study protocol, and is measured as the amount of time hip protectors are
      worn. When reporting use of hip protectors in clinical trials investigators
      should indicate the specific definition of adherence used, explicitly state the
      recommendation that was made for use of hip protectors during the study, and
      describe the methods of recording adherence.

PMID- 14593453
TI  - Limited utility of clinical indices for the prediction of symptomatic fracture
      risk in postmenopausal women.
AB  - Bone mineral density (BMD) is the primary predictor of fracture, and is utilised
      in the definition of osteoporosis. Mass screening for osteoporosis is, however,
      currently not recommended. The primary objective of this study was to develop,
      validate and assess a simple, non-invasive scoring system to identify women at
      high risk of fracture. Using baseline data of the Dubbo Osteoporosis Epidemiology
      Study, a sample of 1256 women aged 60 or above was randomly divided into a
      development cohort (n=846) and a validation cohort (n=410). Low BMD was evaluated
      by DXA, with respect to 2.0 or 2.5 SD below the mean for young normal women at
      the femoral neck and lumbar spine. A logistic regression model was used to derive
      a predictive score, "DOEScore", in the development cohort, and the performance of
      this score was then assessed in the validation cohort. Incident fractures over
      9395 person-years (median of follow-up duration: 8.4 years) were identified by X
      ray records. Approximately 57% and 40% of women (in both cohorts) had T-scores
      less than -2.0 and greater than -2.5, respectively. Only age, body weight, and
      previous fracture were significantly related to BMD at both the femoral neck and
      lumbar spine. These three variables were used in the development of the DOEScore.
      When applied to the validation cohort, the sensitivity and specificity of
      DOEScore were 0.82 and 0.52, respectively, for selecting women with T-scores less
      than -2.5; the area under the receiver operating characteristic (ROC) curve was
      0.75. These goodness-of-fit indices were comparable to, or better than, those
      obtained by the FOSTA, SOFSURF and ORAI score systems. However, neither the
      DOEScore nor other score systems reliably identify women with incident fractures;
      for DOEScore, the sensitivity and specificity were 0.52 and 0.49, respectively,
      with an area under the ROC curve of 0.48. Clinical risk scores can be used to
      identify women likely to have low BMD (albeit with low specificity), but they are
      not a useful tool to identify women who will have a fracture.

PMID- 14593454
TI  - Evaluation of physical capacity and quality of life in osteoporotic women.
AB  - INTRODUCTION: Osteoporotic vertebral fractures result in increased kyphosis
      angle, an alteration that may lead to disturbance in physical capacity.
      OBJECTIVE: We sought to evaluate physical capacity and disability in a group of
      osteoporotic patients. MATERIAL AND METHODS: Fifteen women with osteoporosis and
      vertebral fractures (G1), 20 women with osteoporosis without vertebral fractures
      (G2), and 20 control women (G3) were selected. The variables of physical capacity
      were measured using a treadmill. The patients spent 4 min standing quietly, 4 min
      walking at 3 km/h, and 10 min walking at 4 km/h. The SF-36 questionnaire was also
      applied. RESULTS: The results showed that women with osteoporosis and vertebral
      fractures (G1) had increased kyphosis angle (median 60 degrees ), while the angle
      was 43.5 degrees for G2 and 37 degrees for G3. Oxygen consumption (VO(2) (kg)),
      METS (metabolic equivalent), and energy expenditure (kcal/h) during the standing
      period were higher in G1 than in G2 (G1 vs G2, p=0.016, p=0.017, and p=0.012,
      respectively), whereas no difference in these parameters was observed between
      groups during the walking period. The energy expenditure during walking at 3 km/h
      and at 4 km/h showed a correlation with thoracic kyphosis in G1 (p=0.01 and
      p=0.017, respectively). No difference in SF-36 scores was observed between the
      three groups. CONCLUSION: Energy expenditure showed a correlation with the angle
      of thoracic kyphosis. Patients with or without osteoporosis showed the same
      energy expenditure during the walking period. The SF-36 score was similar for the
      three groups.

PMID- 14593455
TI  - Could apolipoprotein E polymorphisms be hidden behind the relation between bone
      mineral density and atherosclerosis in hemodialysis patients?

PMID- 14593456
TI  - Is there a place for granulocyte colony-stimulating factor in non-neutropenic
      critically ill patients?
AB  - Immunoparalysis, characterised by impairments in neutrophil and
      monocyte/macrophage function, is common in critically ill patients. The
      theoretical ability of granulocyte colony-stimulating factor (G-CSF) to improve
      the functions of both neutrophils and monocytes/macrophages provides a rationale
      for G-CSF therapy in non-neutropenic critically ill patients with infection or a
      high risk of nosocomial infection. The expression of the receptors that mediate G
      CSF effects in neutrophils and monocytes/macrophages is regulated by bacterial
      products, cytokines and endogenous G-CSF levels, accounting for the variables
      effects of G-CSF on the neutrophil functions of critically ill patients. This
      variability should be taken into account when designing studies on the use of G
      CSF in ICU-patients. Studies are still needed to identify the subset of patients
      who may benefit from G-CSF therapy.

PMID- 14593457
TI  - Noninvasive continuous positive airway pressure delivered by helmet in
      hematological malignancy patients with hypoxemic acute respiratory failure.
AB  - OBJECTIVE: To compare the efficacy of early administration of noninvasive
      continuous positive airway pressure (nCPAP) delivered by the helmet vs. face mask
      to treat hematological malignancy patients with fever, pulmonary infiltrates, and
      hypoxemic acute respiratory failure. DESIGN AND SETTING: Prospective clinical
      study with historical matched controls in the hematology department of a
      university hospital. PATIENTS AND INTERVENTIONS: Seventeen hematological
      malignancy patients with hypoxemic acute respiratory failure defined as: moderate
      to severe dyspnea, tachypnea (>30-35 breaths/min), use of accessory muscles and
      paradoxical abdominal motion, and PaO2/FIO2 ratio less than 200. Each patient was
      treated with nCPAP by helmet outside the ICU in the hematological ward. Arterial
      oxygen saturation, heart rate, respiratory rate, and blood pressure were
      monitored to identify early nCPAP failure. Seventeen historical-matched controls
      treated in the same department with face mask CPAP were selected as control
      population; matching criteria were age, sex, diagnosis, and PaO2/FIO2 ratio.
      Primary end-points were improvement in gas exchanges and the need for
      endotracheal intubation. RESULTS: Oxygenation improved in all patients after
      nCPAP. No patient failed helmet nCPAP because of intolerance while eigh patients
      in the mask group did so. nCPAP could be applied continuously for a longer period
      of time in the helmet group (28.44+/-0.20 vs. 7.5+/-0.45 h). CONCLUSIONS: Early
      nCPAP with helmet improves oxygenation in selected immunosuppressed patients with
      hypoxemic acute respiratory failure. Tolerance of helmet nCPAP seems better than
      that of nCPAP delivered by mask.

PMID- 14593458
TI  - Relationship of thyroid function to post-traumatic S-100b serum levels in
      survivors of severe head injury: preliminary results.
AB  - OBJECTIVE: To assess thyroid function abnormalities in survivors of severe head
      trauma and to examine their relationship with indices of brain injury severity.
      DESIGN: Prospective study. SETTING: General intensive care unit (ICU) in a
      university hospital. PATIENTS AND PARTICIPANTS: Twenty-two (21 men) head-injured
      patients, with a median age of 25.5 years at the time of injury, were
      investigated. Severity of brain trauma was assessed by Glasgow Coma Scale (GCS)
      score, Marshall Computerized Tomographic Classification, intracranial pressure
      levels and serum S-100b concentrations measured over a 6-day period.
      INTERVENTIONS: Thyroid function testing was performed 1 year after ICU discharge
      and included the measurement of free thyroxine, triiodothyronine and thyrotropin.
      MEASUREMENTS AND RESULTS: On admission to the ICU, GCS ranged from 3 to 8. Peak S
      100b was 1.49 microg/l (range: 0.37-5.26 microg/l). Median triiodothyronine and
      thyrotropin were 123 ng/dl and 1.60 microIU/ml, respectively. Free thyroxine was
      1.08+/-0.22 ng/dl (range: 0.7-1.5 ng/dl). Overall, 7 of the 22 patients (32%) had
      thyroid dysfunction. Four patients had central hypothyroidism and three patients
      had subclinical hypothyroidism. Peak S-100b correlated negatively with free
      thyroxine (r=-0.47, p=0.02). There were no correlations between other brain
      injury severity indices and thyroid hormone levels. CONCLUSIONS: A significant
      subset of brain injury patients presents with changes in thyroid function 1 year
      after ICU discharge; these depend upon biochemical serum markers of head trauma
      severity.

PMID- 14593460
TI  - [Epidemiology of chronic venous diseases]].
AB  - Chronic venous diseases such as varicosis, post-thrombotic syndrome, and chronic
      venous insufficiency are among the most frequent clinical pictures in the Western
      world. The resultant consequences are persistent complaints such as a feeling of
      heaviness, tendency for swelling, and leg pain as well as vast skin changes
      culminating in an open leg ulcer. Although a series of past epidemiological
      studies are available, they are quite inconsistent with regard to implementation
      and definition of the clinical picture so that they cannot always be compared.
      Some are based solely on registration of disease history by questionnaires, which
      are inadequate to reliably assess actual prevalence. In only a very few studies
      are the results based on the actual examination of the subjects. Moreover,
      entirely difference age intervals and random samples are evaluated. The present
      study summarizes the most important epidemiological results with particular
      regard to the current Bonn Vein Study.

PMID- 14593459
TI  - Biomechanical and morphometric intestinal remodelling during experimental
      diabetes in rats.
AB  - AIMS/HYPOTHESIS: Morphometric and passive biomechanical properties were studied
      in the duodenum, jejunum and ileum in 10 non-diabetic and 40 streptozotocin
      induced diabetic rats. METHODS: The diabetic rats were divided into groups living
      4 days, 1, 2, and 4 weeks after diabetes was induced ( n=10 for each groups). The
      mechanical test was done as a ramp distension experiment. The intestinal diameter
      and length were obtained from digitised images of the intestinal segments at pre
      selected pressures and at no-load and zero-stress states. Circumferential and
      longitudinal stresses (force per area) and strains (deformation) were computed
      from the length, diameter and pressure data and from the zero-stress state
      geometry. RESULTS: The blood glucose concentration increased four- to fivefold in
      the diabetic rats. Streptozotocin-induced diabetes generated pronounced increase
      in the weight per centimetre length, wall thickness and wall cross-sectional area
      in all intestinal segments during diabetes ( p<0.05). Histological analysis
      showed that the thickness of the intestinal layers was increased in all segments
      during diabetes ( p<0.05). In the duodenum the opening angle did not change in
      the first 2 weeks and decreased after 4 weeks ( p<0.05). In the jejunum and ileum
      the opening angle increased after 1 week in the diabetic group. The residual
      strain showed the same pattern as the opening angle. Furthermore, it was found
      that the circumferential and longitudinal stiffness of the intestinal wall
      increased with the duration of diabetes ( p<0.05 and p<0.01).
      CONCLUSION/INTERPRETATION: Morphological and biomechanical remodelling of the
      small intestine occurred during the development of diabetes.

PMID- 14593461
TI  - [Compression therapy in chronic venous insufficiency. New test procedures and
      therapeutic options].
AB  - Chronic venous insufficiency (CVI) has a significant socioeconomic impact. The
      existent venous hypertension and the subsequent capillary hypertension result in
      trophic skin damage culminating in an ulcer. Venous ulcers affect 1-3% of the
      adult population. Compression therapy provides the basis for noninvasive
      treatment of CVI. It can be applied alone or in combination with invasive
      strategies. A variety of materials are available for phlebological compression
      therapy in the form of compression bandages and compression hosiery. Knowledge of
      the different qualities of the compression materials and their mode of action is
      important in choosing the correct means of compression with regard to clinical
      findings and the patient's needs. As far as possible, the compression method
      applied should be monitored for any loss of effectivity during regular follow-up
      examinations of the patients. The following article deals with this topic. A new
      option for compression therapy of crural ulcers is presented and the possibility
      for checking the effectiveness of the compression stockings during outpatient

PMID- 14593462
TI  - [Wound debridement and treatment of ulcus cruris. Conservative and operative
      therapeutic procedures].
AB  - Effective debridement of necrotic tissue and wet wound conditions are essential
      for wound healing. This can be achieved surgically or with conservative measures.
      Non-surgical options are the use of enzymatic preparations and the application of
      maggots. This biosurgical approach is enjoying a renaissance. The underlying
      pathophysiology of chronic venous leg ulcers can only be addressed by compression
      therapy and vein surgery.

PMID- 14593463
TI  - [Therapy of ulcus cruris venosum].
AB  - Wound healing in venous leg ulcers is a highly complex, dynamic process that is
      influenced by a number of factors. The primary task of local therapy is to
      support this natural healing process. While a number of therapeutic agents are
      available, in most cases their efficacy has yet to be established in controlled
      prospective studies in the sense of evidence-based medicine. Thus, the physician
      is left with the task of drawing up individual therapy plans for each patient
      according to the state of the wound. Compression bandages or stockings form the
      mainstay of treatment, generally in combination with moist dressings for chronic
      wounds.

PMID- 14593464
TI  - [Current status of sclerotherapy of varicose veins].
AB  - Sclerotherapy is a therapeutic technique now perfectly adapted to all types and
      sizes of varicose veins. Its goals are to close the lumen and reduce the diameter
      of the varicosity. These objectives can only be achieved by following a strict
      protocol. This treatment always starts with the large venous trunks such as the
      saphenous veins which are located deep and best treated with Duplex-guided
      sclerotherapy. Then the collateral and reticular veins can be directly sclerosed.
      Superficial starburst veins and telangiectases should only be approached after
      all feeder vessels have been treated. For these reasons, a detailed clinical
      examination should be combined with duplex sonographic investigations before any
      therapy is attempted. When these rules are observed, sclerotherapy is a very
      effective treatment.

PMID- 14593465
TI  - [Conditioning of chronic wounds with proteolytic enzymes].
AB  - In the past few years, several different proteolytic enzymes have been shown to
      be effective in conditioning the chronic wound beds. The use of proteolytic
      enzymes in wound-bed preparation enables a selective painless debridement.
      Moreover multiple positive effects on formation of granulation tissue and re
      epithelialization have been observed. Therefore, a faster overall healing of
      chronic wounds may result. Moreover, numerous positive effects on a rapid
      induction of granulation are discussed. The supporting data do not fulfill the
      criteria of evidence-based medicine. For most chronic wounds today, enzymatic
      debridement represents a first choice method especially for outpatients and
      perhaps in combination with surgical debridement.

PMID- 14593466
TI  - [Necrotizing otitis externa caused by Stenotrophomonas maltophilia].
AB  - The gram-negative bacterium Stenotrophomonas maltophilia is feared, especially in
      intensive care wards, as a nosocomial opportunistic pathogen causing fulminant
      septicemia and organ failure in immunosuppressed patients. A patient with chronic
      lymphocytic leukemia developed a cutaneous infection with the clinical pattern of
      necrotizing otitis externa.

PMID- 14593467
TI  - [Congenital and postpartum ungues incarnati].
AB  - A 2 month old infant presented with ingrown toenails of both great toes with an
      accompanying inflammatory reaction. The appearance of the toenails became normal
      after 6 months of topical antiseptic and anti-inflammatory treatment.

PMID- 14593469
TI  - [HIV-positive patient with multiple ulcers. Lues maligna].

PMID- 14593470
TI  - [Current developments in syphilis. Prevention].

PMID- 14593471
TI  - [Report of the 9th Psoriasis Specialty Congress, Bad Bentheim, 5 April 2003].

PMID- 14593468
TI  - [Squamous epithelial carcinomas of the face with neurotropic growth].
AB  - BACKGROUND AND OBJECTIVE: Invasion of squamous cell carcinoma of the head and
      neck into cutaneous nerves is rare and can easily be missed. Perineural outgrowth
      into cerebral nerves may result in severe pain or neurological disturbances. In
      addition, these carcinomas more often recur or metastasize and therefore are
      associated with a poor prognosis. PATIENTS/METHODS: We report on two patients
      with squamous cell carcinoma of the dorsum of the nose and lower lip exhibiting
      neurotropic growth. RESULTS: Histology showed pleomorphic keratinocytes growing
      deep into the subcutaneous tissue and bone, respectively. The presence of few
      pleomorphic keratinocytes could be only confirmed by immunohistochemistry, though
      indicated by a perineural lymphocytic infiltrate. In both patients, several re
      excisions were necessary to achieve cure. CONCLUSIONS: In neurotropic squamous
      cell carcinoma a consequent radical micrographic surgery as well as neurological
      and radiological investigations are mandatory. We also review the literature.

PMID- 14593474
TI  - Late onset of Imerslund-Grasbeck syndrome without proteinuria in four children of
      one family from the Lebanon.

PMID- 14593475
TI  - Coxsackievirus B3-induced myocarditis: differences in the immune response of
      C57BL/6 and Balb/c mice.
AB  - Coxsackievirus B3 (CVB3) infections are the most frequent causes of human
      myocarditis, often resulting in chronic stages characterized by fibrosis and loss
      of function. This disease is called dilated cardiomyopathy (DCM). Persistent
      virus in the myocardium may lead to chronic activation of fibroblasts, and
      subsequently, to fibrosis of the myocardium. Studies with immunodeficient mice
      have shown that certain defects of the immune system retard the rate at which
      virus is eliminated from the heart, thus leading to viral persistence. Therefore,
      we followed the immune response of two immunocompetent mouse strains (C57BL/6 and
      Balb/c) to CVB3 infection. These two strains have been reported to develop
      different immune responses to infections and we expected a similar reaction to
      viral infections as well. The two mouse strains recovered completely from CVB3
      infection and expressed identical levels of cytokine mRNA in the heart. However,
      the virus in heart tissue decreased more slowly in Balb/c than in C57BL/6 mice.
      This was accompanied by a strong virus-specific IgG and weak IgM response in the
      C57BL/6 mice, in comparison to the Balb/c mice. We conclude, therefore, that
      viral-specific IgG is of importance for CVB3 elimination from infected hearts.

PMID- 14593476
TI  - Production of monoclonal antibodies and development of an antigen capture ELISA
      directed against the envelope glycoprotein GP of Ebola virus.
AB  - Ebola virus (EBOV) causes severe outbreaks of Ebola hemorrhagic fever in endemic
      regions of Africa and is considered to be of impact for other parts of the world
      as an imported viral disease. To develop a new diagnostic test, monoclonal
      antibodies to EBOV were produced from mice immunized with inactivated EBOV
      species Zaire. Antibodies directed against the viral glycoprotein GP were
      characterized by ELISA, Western blot and immunofluorescence analyses. An antigen
      capture ELISA was established, which is specific for EBOV-Zaire and shows a
      sensitivity of approximately 10(3) plaque-forming units/ml. Since the ELISA is
      able to detect even SDS-inactivated EBOV in spiked human sera, it could
      complement the existing diagnostic tools in the field and in routine laboratories
      where high containment facilities are not available.

PMID- 14593477
TI  - Expression and localization of type III secretion-related proteins of Chlamydia
      pneumoniae.
AB  - The entire developmental cycle of the obligate intracellular bacteria Chlamydia
      pneumoniae takes place within the inclusion body. As many gram negative bacteria,
      Chlamydia possess a type III-secretion system (TTSS), which allows them to target
      effector molecules into the host cell. The expression and localization of several
      proteins constituting the TTSS apparatus and of proteins supposed to be secreted
      by the TTSS have been investigated. For the TTSS-constituting proteins, we
      selected representatives such as YscN (ATPase), LcrE (putative "lid" of the TTSS)
      and LcrH1 (postulated to be a chaperone). Furthermore, we focused on the putative
      effector proteins IncA, IncB, IncC, Cpn0809 and Cpn1020. Expression of these
      proteins was detected by reverse transcriptase-PCR followed by immunoblot
      analysis using antisera that were generated against the corresponding recombinant
      proteins. Thereby, expression could be detected on the RNA and/or protein level.
      Intracellular localization of proteins under investigation was determined by
      immunofluorescence assays using the respective antisera. YscN was shown to be
      distributed equally throughout the inclusion body, whereas LcrE gave a more
      prominent staining of the inclusion membrane. IncA was detected mainly on the
      membrane of the inclusion body, whereas IncB and IncC were shown to be located
      within the inclusion. Immunofluorescence assays with antisera raised against
      Cpn0809 and Cpn1020 showed completely different labeling. Signals corresponding
      to Cpn0809 and Cpn1020 were distributed within the host cell rather than inside
      the inclusions. Taken together, the different localization patterns of the
      effector proteins indicate differences in function and interplay with the host
      cell.

PMID- 14593478
TI  - Characterization of hey bHLH genes in teleost fish.
AB  - Hairy-related basic helix-loop-helix (bHLH) transcription factors are targets of
      Delta-Notch signaling and represent essential components for a number of cell
      fate decisions during vertebrate embryogenesis. Hey genes encode a subfamily of
      hairy-related proteins that have been implicated in processes like somitogenesis,
      blood vessel and heart development. We have identified and characterized hey
      genes in three teleost fish lineages using degenerate PCR and database searches.
      Phylogenetic analysis of Hey proteins suggests a complex pattern of evolution
      with high divergence of hey2 in Takifugu rubripes (Fugu, Japanese pufferfish) and
      possibly loss in the related Tetraodon nigroviridis (the freshwater pufferfish).
      In addition, duplication of hey1 in both pufferfishes, Fugu and Tetraodon, was
      observed. Conversely, zebrafish (Danio rerio) has the same complement of three
      hey genes as known from mammals. All three hey genes show much more restricted
      gene expression profiles in zebrafish when compared to mouse. Importantly, while
      all three murine Hey genes are expressed in overlapping patterns in the
      presomitic mesoderm (PSM) and somites, in zebrafish only hey1 shows PSM and
      somite expression in a highly dynamic fashion. Therefore, while overlapping
      expression might account for redundancy of hey function in higher vertebrates,
      this is unlikely to be the case in zebrafish. In deltaD (dlD) deficient after
      eight zebrafish mutants, the dynamic expression of hey1 in the PSM is impaired
      and completely lost in newly formed somitomeres. Overexpression of dlD on the
      other hand results in the ectopic expression of hey1 in the axial mesoderm.
      Hence, hey1 represents a target of Delta-Notch signaling dynamically expressed
      during somite formation in zebrafish.

PMID- 14593479
TI  - Prospero and Snail expression during spider neurogenesis.
AB  - Analysis of early neurogenesis in the spider Cupiennius salei (Chelicerata,
      Aranea, Ctenidae) has shown that the cells of the central nervous system are
      recruited from clusters of cells that invaginate from the neuroectoderm. This is
      in contrast to Drosophila, where only single cells delaminate and become
      neuroblasts, the stem cells of the nervous system. In order to compare the
      processes further, we have cloned homologues of the pan-neural Drosophila genes
      prospero and snail from the spider and have analysed their RNA and protein
      expression pattern. We find that snail expression is transient and only a subset
      of neural cells expresses Snail protein at any given time, making it difficult to
      assess whether it is indeed a pan-neural gene in the spider. Prospero protein
      expression, on the other hand, is seen in all invaginating cells and continues
      throughout differentiation of the neurons. In contrast to Drosophila, asymmetric
      localization cannot be detected, even in cells that still divide. Our results
      provide no evidence for neuroblasts or stem cells in the spider, although there
      are a limited number of mitoses in the cells that are derived from the
      invaginating clusters. These aspects of spider neurogenesis are more similar to
      the neurogenesis process known from vertebrates.

PMID- 14593480
TI  - The role of amylomaltase in maltose metabolism in the cytosol of photosynthetic
      cells.
AB  - Transitory starch is stored during the day inside chloroplasts and then broken
      down at night for export. Recent data indicate that maltose is the major form of
      carbon exported from the chloroplast at night but its fate in the cytosol is
      unknown. An amylomaltase gene ( malQ) cloned from Escherichia coli is necessary
      for maltose metabolism in E. coli. We investigated whether there is an
      amylomaltase in the cytosol of plant leaves and the role of this enzyme in
      plants. Two mutants of Arabidopsis thaliana (L) Heynh. were identified in which
      the gene encoding a putative amylomaltase enzyme [ disproportionating enzyme 2,
      DPE2 (DPE1 refers to the plastid version of this enzyme)] was disrupted by a T
      DNA insertion. Both dpe2-1 and dpe2-2 plants exhibited a dwarf phenotype and
      accumulated a large amount of maltose. In addition, dpe2 mutants accumulated
      starch and a water-soluble, ethanol/KCl-insoluble maltodextrin in their
      chloroplasts. At night, the amount of sucrose in dpe2 plants was lower than that
      in wild-type plants. These results show that Arabidopsis has an amylomaltase that
      is involved in the conversion of maltose to sucrose in the cytosol. We
      hypothesize that knocking out amylomaltase blocks the conversion from maltose to
      sucrose, and that the higher amount of maltose feeds back to limit starch
      degradation reactions in chloroplasts. As a result, dpe2 plants have higher
      maltose, higher starch, and higher maltodextrin but lower nighttime sucrose than
      wild-type plants. Finally, we propose that maltose metabolism in the cytosol of
      Arabidopsis leaves is similar to that in the cytoplasm of E. coli.

PMID- 14593481
TI  - Environmental tobacco smoke exposure among pregnant women: impact on fetal
      biometry at 20-24 weeks of gestation and newborn child's birth weight.
AB  - AIM: While there are sufficient data regarding the negative effect of exposure to
      the constituents of tobacco smoke on newborn infants' birth weights, it is still
      unclear whether this effect may originate in early pregnancy. The aim of the
      present study was to evaluate the impact of exposure to tobacco smoke components
      in early pregnancy (20-24 weeks) on fetal biometry. METHODS: The study population
      comprised 183 women consecutively enrolled at 20-24 weeks of pregnancy at the two
      antenatal care units. Ultrasound biometric measurements of fetal bi-parietal
      diameter (BPD), abdominal circumference (AC) and femur length (FL) were performed
      at the time of enrollment. Serum cotinine concentration was determined at 20-24
      weeks of gestation by gas chromatography with mass spectrometry detector (GC/MS)
      to assess environmental tobacco smoke (ETS) exposure during the previous evening
      and the morning of the same day (blood collection at 1200-1300 h). ETS exposure
      (passive smoking) was assumed to occur when the level of serum cotinine ranged
      from 2-10 ng/ml. RESULTS: In a multiple regression model for bi-parietal diameter
      (BPD), after adjustment for pregnancy duration at the time of ultrasound
      examination, fetal gender, and maternal pre-pregnancy weight, a statistically
      significant negative association was found between the BPD and serum cotinine
      concentration. A similar association was identified for subjects with serum
      cotinine concentrations below 10 ng/ml (corresponding to passive smoking)
      (P=0.06). After controlling for pregnancy duration, maternal pre-pregnancy weight
      and infant's gender, we found that serum cotinine levels at 20-24 weeks of
      gestation was inversely associated with infant birth weight (P=0.004). For the
      subjects with serum cotinine levels below 10 ng/ml, a borderline association
      (P=0.09) with infant birth weight was found. CONCLUSIONS: Maternal exposure to
      tobacco smoke in early pregnancy, as measured by serum cotinine concentrations at
      20-24 weeks of gestation, adversely affects fetal BPD. Preventive measures need
      to be undertaken to encourage pregnant women to stop smoking and avoid passive
      exposure to tobacco smoke from the very beginning of pregnancy.

PMID- 14593482
TI  - A neocartilage ideal for extracellular matrix macromolecule immunolocalization.
AB  - A neocartilage construct readily amenable to microscopy and biomechanical studies
      is described. Porcine articular cartilage was digested with a mixture of dispase
      and collagenase for chondrons or pronase and collagenase for chondrocytes.
      Chondrons or chondrocytes plated in 96-well plates were fixed and immunolabeled
      in situ for fluorescence microscopy at days 4 and 11. Collagen types I and II,
      aggrecan, and MMP-13 expression was assayed by semiquantitative RT-PCR. Cell
      numbers were analyzed by MTT assay. Chondrons and chondrocytes produced
      neocartilage that could be handled with minimal tearing on day 3 and none on day
      11. Some cell division occurred between days 4 and 7. In both cultures,
      chondrocytes were surrounded by a thin rim of type VI collagen and osteopontin.
      Type II collagen, keratan sulfate, and tenascin were abundant throughout. At day
      3, cells were rounded but by day 11 flattened cells were visible in the
      substratum. Continued synthesis of aggrecan and type II collagen mRNA indicated
      maintenance of the chondrocyte phenotype. The neocartilage was easy to
      immunolabel in situ without the need for sectioning, and individual cells were
      readily observed by microscopy. The versatility of these constructs makes them
      ideal for microscopy and for biomechanical studies.

PMID- 14593483
TI  - Mitochondrial DNA D-loop hypervariable regions: Czech population data.
AB  - In order to identify polymorphic sites and to find out their frequencies and the
      frequency of haplotypes, the complete D-loop of mitochondrial DNA (mtDNA) from 93
      unrelated Czech Caucasians was sequenced. Sequence comparison showed that 85
      haplotypes were found and of these 78 were unique, 6 were observed twice and 1
      was observed three times. Genetic diversity (GD) was estimated at 0.999 and the
      probability of two randomly selected sequences matching (random match
      probability, RMP) at 1.2%. Additionally these calculations were carried out for
      hypervariable regions 1, 2 (HV1, HV2), for the area between HV1 and HV2 and for
      the area of the hypervariable region HV3. The average number of nucleotide
      differences (ANND) was established to be 10.2 for the complete D-loop. The
      majority of sequence variations were substitutions, particularly transitions.
      Deletions were found only in the region where HV3 is situated and insertions in
      the same place and in poly-C tracts between positions 303 and 315 in HV2. A high
      degree of length heteroplasmy was found especially in the regions of poly-C
      tracts between positions 16184 and 16193 in HV1 and between positions 303 and 315
      in HV2. Position heteroplasmies were found in two cases.

PMID- 14593484
TI  - Mitochondrial DNA control region diversity in hairs and body fluids of
      monozygotic triplets.
AB  - Length heteroplasmy of the homopolymeric cytosine stretch in the hypervariable
      region II of the mitochondrial D-loop was investigated in blood, buccal cells and
      hair shafts of monozygotic triplets. The proportions of length heteroplasmy were
      determined by cloning and sequencing of multiple independent clones. Blood and
      buccal cells showed an accumulation of molecules with one and two insertions of
      cytosine residues in relation to the Cambridge Reference Sequence (CRS). The
      results did not show statistically significant differences between blood and
      buccal cells of one and the same individual and also not between the three
      monozygotic brothers. In the hair samples a loss of cytosine residues was
      established in all three monozygotic individuals compared to blood and buccal
      cells, suggesting that this must be a regular process. Furthermore, the hair
      shaft samples showed significant differences between the frequencies of 7, 8 or 9
      Cs in the poly C region comparing the three individuals (p<0.008) and in addition
      there were highly significant differences (p<0.0001) when comparing the results
      for six different hairs of each individual separately. From these results it can
      be assumed that besides a common genetic bottleneck during embryonic development,
      a post-embryonic bottleneck seems to exist in each hair follicle.

PMID- 14593486
TI  - BISS: concept and biomechanical investigations of a new screw system for
      electromagnetically induced internal osteostimulation.
AB  - INTRODUCTION: The aim of an intraosseous application of electromagnetic
      alternating fields is to speed up both the regeneration of osteonecroses and bone
      regeneration. In clinical studies, the efficiency of the technique could be
      successfully proven by using a transducer coil. The advantage of the traditional
      technique was the variety of its applications in connection with various
      osteosynthesis systems; the disadvantage was a possible failure of the contacting
      leads and the resulting functional breakdown. MATERIALS AND METHODS: A newly
      developed BISS screw (bipolar induction screw system) with integrated coil and
      electrodes was compared to a standard cannulated screw used in the traditional
      technique. The strength of BISS screws ( n=6) and of cannulated screws ( n=6) was
      evaluated in comparative biomechanical tests. Examinations consisted of torsional
      and static and dynamic cantilever tests. All screws were made of the same
      material (TiAl(6)V(4)) and had identical outer dimensions. RESULTS: No
      significantly lower strengths could be observed when we compared BISS screws with
      cannulated screws. The BISS screws even showed significantly higher mechanical
      values due to a reinforcing effect by the attached electrode. CONCLUSION: In the
      modified concept of the new BISS screw, both coil and electrodes are housed in
      only one cannulated screw. No negative effects concerning mechanical strength and
      durability were associated with the new screw concept. This provides for a
      simpler implantation and makes removal easier, while the risk of a cable tear is
      avoided.

PMID- 14593485
TI  - The lazaroid tirilazad is a new inhibitor of direct and indirect UVA-induced
      lipid peroxidation in human dermal fibroblasts.
AB  - Lipid peroxidation caused by oxidative stress within the tissue leads to
      destruction and dysfunction of cellular membranes. Human dermal fibroblasts in
      the skin are subject to constant photooxidative stress caused mainly by deeply
      penetrating UVA irradiation. Therefore, the membrane damage caused by this
      photooxidative stress may be a major promoter of photoaging and photocarcinogenic
      processes initiated and promoted by long-term UVA exposure of the skin. The
      oxidative destruction is counterbalanced by a complex network of enzymatic and
      nonenzymatic antioxidants creating the skin's line of defence against UVA-induced
      reactive oxygen species. The lazaroid tirilazad represents a new synthetic group
      of antioxidants with structural molecular similarity to glucocorticosteroids. We
      investigated the antioxidative capacity of tirilazad by determining its effects
      on the levels of malondialdehyde (MDA), as a marker of lipid peroxidation,
      induced directly or indirectly by UVA in human dermal fibroblasts. In a time- and
      dose-dependent kinetic, we demonstrated that fibroblasts incubated with tirilazad
      are well protected against subsequent UVA irradiation and show no increase in MDA
      levels similar to the unirradiated controls. This was also observed when lipid
      peroxidation was caused chemically by incubation of human dermal fibroblasts with
      200 micro M Fe(3+)-citrate and 1 m M ascorbyl phosphate as a model of indirect
      UVA-induced skin damage. Lysates of fibroblasts treated this way showed a tenfold
      increase in MDA levels, whereas preincubation with tirilazad resulted in a
      significantly lower increase in MDA levels. Furthermore, in a comparison with the
      well-established radical scavenger Trolox, an alpha-tocopherol analogue,
      tirilazad offered better protection to the membranes. Our results demonstrate for
      the first time that the lazaroid tirilazad is an effective inhibitor of direct
      and indirect UVA-induced increases in MDA as a marker of lipid peroxidation in
      human dermal fibroblasts.

PMID- 14593488
TI  - Synchrotron radiation in radiology: novel X-ray sources.
AB  - X-rays, the key ingredient of radiology, are still primarily produced with the
      mechanism discovered by Rontgen over one century ago. A different approach,
      however, is becoming increasingly important: the use of synchrotron sources based
      on fast-moving electrons and on their relativistic properties. We discuss the
      elements of this new strategy, its practical implementation, and some new types
      of synchrotron sources under development. The present and potential impact on
      radiology of different classes of synchrotron sources is briefly and
      realistically analyzed.

PMID- 14593487
TI  - Effects of leg movements on the synaptic activity of descending statocyst
      interneurons in crayfish, Procambarus clarkii.
AB  - Crustacean postural control is modulated by behavioral condition. In this study,
      we investigated how the responses of descending statocyst interneurons were
      affected during leg movements. Intracellular recording was made from an animal
      whose statoliths had been replaced with ferrite grains so that statocyst
      receptors could be activated by magnetic field stimulation. We identified 14
      morphological types of statocyst-driven descending interneurons. Statocyst-driven
      descending interneurons always showed an excitatory response to statocyst
      stimulation on either ipsilateral or contralateral side to the axon. The response
      of each statocyst-driven descending interneuron to statocyst stimulation was
      differently modulated by leg movements in different conditions. During active leg
      movements, six statocyst-driven descending interneurons were activated regardless
      of whether a substrate was provided or not. In other two statocyst-driven
      descending interneurons, the excitatory input during leg movements was stronger
      when a substrate was provided than when it was not. One statocyst-driven
      descending interneuron received an excitatory input only during leg movements on
      a substrate, whereas another statocyst-driven descending interneuron did not
      receive any input during leg movements both on a substrate and in the air. These
      results suggest that the descending statocyst pathways are organized in parallel,
      each cell affected differently by behavioral conditions.

PMID- 14593489
TI  - Comparison of serum nitric oxide levels in active juvenile rheumatoid arthritis
      with those of patients in remission.
AB  - Thirty-four children with juvenile rheumatoid arthritis were studied for
      surrogate markers of increased nitric oxide (NO) production by spectrophotometry.
      Mean levels of reactive nitrogen intermediates and citrulline levels were higher
      in patients with active disease than in children with partial and complete
      remission. A significant correlation was also found between clinical indices of
      inflammation, erythrocyte sedimentation rate, modified Childhood Health
      Assessment Questionnaire scores, and surrogate markers of increased NO
      production.

PMID- 14593490
TI  - Cytokine profile in serum and synovial fluid of arthritis patients with Chlamydia
      trachomatis infection.
AB  - Chlamydia trachomatis (Ct)-induced arthritis (CtIA) is characterized by
      persistent Ct infection, which stimulates secretion of cytokines in vitro. We
      therefore investigated whether CtIA patients have a unique cytokine profile in
      synovial fluid or serum in vivo. Because underlying Ct infection is overlooked in
      a high percentage of patients with initially diagnosed undifferentiated
      oligoarthritis (UOA), we examined whether determination of cytokines might also
      be of diagnostic relevance for this arthritis form. Matched serum and synovial
      fluid specimens from 26 patients with CtIA were analyzed and compared to those
      from 34 patients with UOA in whom Ct infection was excluded and those of nine
      patients with rheumatoid arthritis (RA). In 15 CtIA patients, Ct DNA from
      synovial fluid could be amplified by polymerase chain reaction. The following
      cytokine or cytokine antagonists were measured by enzyme-linked immunosorbent
      assay: interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, IL-6, IL-1
      receptor antagonist, and soluble TNF receptor p75. No statistically significant
      differences in cytokine levels between patients with CtIA or the other arthritis
      forms were detected. Also, comparison between CtIA patients with (n = 17) and
      without Chlamydia DNA (n = 9) in synovial fluid revealed no significant
      differences for these cytokines. Cytokine levels in serum and synovial fluid were
      not different between CtIA, UOA without Ct infection, and RA patients. The
      intracellular presence of Ct was not associated with a specific profile of these
      cytokines in vivo.

PMID- 14593491
TI  - Paraneoplastic remitting seronegative symmetrical synovitis with pitting edema
      (RS3PE syndrome): a report of two cases and review of the literature.
AB  - We report two cases of paraneoplastic remitting seronegative symmetrical
      synovitis with pitting edema (RS3PE) associated with prostatic adenocarcinoma.
      One of the patients was positive for Helicobacter pylori and the other had
      secondary bone metastases. In the latter, the clinical picture of RS3PE developed
      after surgical intervention for the primary lesion. On physical examination,
      while the hands and feet were swollen in the first patient, pitting edema was
      present only at the feet of the other. All joints of the affected hands and feet
      were painful. Serological tests including rheumatoid factor, antinuclear
      antibody, and human leukocyte antigen B27 were all negative. Response to low-dose
      corticosteroid treatment was delayed in the first patient, but the symptoms were
      relieved better in the second one.

PMID- 14593492
TI  - Methotrexate and the rheumatoid lung: a riddle wrapped in an enigma.

PMID- 14593493
TI  - Recurrent transverse myelitis in primary antiphospholipid syndrome--case report
      and literature review.
AB  - Transverse myelitis is an uncommon but well-known neurologic complication of
      systemic lupus erythematosus, and antiphospholipid antibodies have been
      implicated as having a pathogenic role of myelopathy in primary and secondary
      antiphospholipid syndrome. Transverse myelitis usually is monophasic, but
      recurrent transverse myelitis was reported in association with systemic lupus
      erythematosus, multiple sclerosis, and spinal arteriovenous malformations. It has
      been reported extremely rarely in patients with primary antiphospholipid
      syndrome. Herein we describe a patient with both conditions and propose that
      recurrent transverse myelitis should be included as a very rare feature of
      primary antiphospholipid syndrome.

PMID- 14593494
TI  - Differential diagnosis of optic neuritis in a patient with ankylosing
      spondylitis.
AB  - The authors report a 38-year-old white man with ankylosing spondylitis (AS) who
      presented with recurrent ischaemic optic neuritis. The initial diagnosis was of
      multiple sclerosis, but further investigation showed serology and cerebrospinal
      fluid culture positive for syphilis. After treatment for tertiary syphilis with
      penicillin, there was complete remission of the ocular symptoms. This case
      illustrates the differential diagnosis of optic neuritis in AS and supports the
      relevance of investigating infectious diseases in the management of ischaemic
      optic neuritis.

PMID- 14593495
TI  - Clinical and genetic risk factors of herpes zoster in patients with systemic
      lupus erythematosus.
AB  - OBJECTIVE: The aim of this study was to determine the clinical and genetic risk
      factors that influence herpes zoster occurrence in patients with systemic lupus
      erythematosus (SLE). METHODS: Three hundred three SLE patients meeting the
      American College of Rheumatology criteria were enrolled in this study. Herpes
      zoster was diagnosed when classic grouped vesicles were noted. Medical records
      were reviewed retrospectively to collect clinical information. For Fc gamma
      receptor IIa (Fc gamma RIIa) and Fc gamma RIIIa genotyping, polymerase chain
      reaction (PCR) using allele-specific primers was performed. The PCR sequence
      specific oligonucleotide probe method was utilized in human HLA-DRB1 genotyping.
      RESULTS: Forty-two cases (13.9%) of zoster occurred among 303 SLE patients. The
      incidence of zoster in patients with SLE was 32.5/1,000 patients per year.
      Patients who developed zoster had higher rates of lupus nephritis (P = 0.018) and
      positive anti-Sm antibody (P = 0.019). However, Fc gamma RIIa and Fc gamma RIIIa
      polymorphism and the HLA-DRB1 genotype did not influence herpes zoster
      occurrence. CONCLUSION: Systemic lupus erythematosus patients with lupus
      nephritis or anti-Sm antibody are at higher risk of herpes zoster. Fc gamma RIIa
      (H/R131), Fc gamma RIIIa (F/V176), and HLA-DRB1 genetic polymorphisms did not
      influence the occurrence of herpes zoster in these patients.

PMID- 14593496
TI  - Quercetin inhibits the invasion of murine melanoma B16-BL6 cells by decreasing
      pro-MMP-9 via the PKC pathway.
AB  - PURPOSE: On the basis of the inhibitory effect of quercetin on the invasion of
      melanoma B16-BL6 cells previously reported by us, the mechanisms of quercetin
      mediated inhibition of invasion were further investigated in the present study.
      METHODS: The ability of B16-BL6 cells to invade and migrate was evaluated in
      terms of the numbers of cells penetrating a reconstituted basement membrane in
      the Transwell coculture system. The relative levels and activities of matrix
      metalloproteinase-9 (MMP-9) and MMP-2 were determined by gelatin zymography and
      quantified using LabWorks 4.0 software. RESULTS: The quercetin-mediated
      inhibition of invasion was partially blocked by phorbol-12,13-dibutyrate (PDB), a
      PKC (protein kinase C) activator, and by doxorubicin, a PKC inhibitor. Only the
      proforms of MMP-9 (92 kDa) and MMP-2 (72 kDa) were detected by gelatin
      zymography. Quercetin dose-dependently decreased the gelatinolytic activity of
      pro-MMP-9. Doxorubicin also markedly reversed the quercetin-induced decrease.
      Quercetin showed a dose-dependent antagonism of increases in gelatinolytic
      activity of pro-MMP-9 induced by PDB and free fatty acid (another PKC activator).
      CONCLUSIONS: Together with the report that quercetin directly reduces PKC
      activity, the results reported here suggest that quercetin may inhibit the
      invasion of B16-BL6 cells by decreasing pro-MMP-9 via the PKC pathway.

PMID- 14593498
TI  - Derangement of immune responses by myeloid suppressor cells.
AB  - In tumor-bearing mice and cancer patients, tumor progression is often associated
      with altered hematopoiesis leading to the accumulation of myeloid cells.
      Extensive studies in preclinical models indicate that these cells share the CD11b
      and the Gr-1 markers, possess a mixed mature-immature myeloid phenotype, and are
      responsible for the induction of T-cell dysfunctions, both tumor-specific and
      nonspecific. Moreover, CD11b(+)Gr-1(+) myeloid cells are described under
      different unrelated situations associated with temporary impairment of the T
      lymphocyte reactivity. This review examines recent findings on the nature,
      properties, and mechanisms of action of these myeloid suppressor cells (MSCs).

PMID- 14593497
TI  - LY317615 decreases plasma VEGF levels in human tumor xenograft-bearing mice.
AB  - Angiogenesis plays an important role in tumor growth. Angiogenic growth factors
      may be useful as biomarkers of antiangiogenic activity since their plasma
      concentrations correlate with the efficacy of treatments directed toward
      angiogenic targets. SW2 small-cell lung carcinoma (SCLC), Caki-1 renal cell
      carcinoma and HCT-116 colon carcinoma tumors produce measurable plasma VEGF, bFGF
      and TGFbeta in nude mice. Mice bearing these human tumor xenografts were treated
      orally twice daily with the PKCbeta inhibitor, LY317615 (days 14-30 for SW2 and
      HCT116, and days 21-39 for Caki-1). Plasma was collected every 3 days from
      control and treated mice. LY317615 significantly decreased plasma VEGF levels in
      mice bearing SW2 SCLC and Caki-1 renal cell carcinoma compared to control plasma
      concentrations beginning 5-7 days after initiating therapy. VEGF plasma levels
      remained suppressed after termination of LY317615 treatment and for the duration
      of the study (an additional 2 to 3 weeks). Plasma VEGF levels in mice bearing
      HCT116 xenografts were not altered by LY317615 treatment and plasma bFGF and TGF
      beta were not altered by LY317615 in any of the animals. As shown by CD31
      immunohistochemical staining, LY317615 decreased intratumoral vessel density by
      nearly 40% in all three tumors. Only the Caki-1 tumor responded to single-agent
      LY317615 therapy with a measurable tumor growth delay. Thus, unexpectedly
      inhibition of PKCbeta in vivo led to decreased VEGF production that persisted
      after therapy as well as to decreased intratumoral vessels. Plasma VEGF was a
      weak marker of response to LY317615, and plasma bFGF and TGFbeta were not markers
      of LY317615 activity.

PMID- 14593499
TI  - Signal transducer and activator of transcription 6 (Stat6) and CD1: inhibitors of
      immunosurveillance against primary tumors and metastatic disease.
AB  - Many tumor immunologists favor the hypothesis that optimal anti-tumor activity is
      mediated by type 1 CD4(+) and CD8(+) T cells, and that the production of type 2
      CD4(+) T cells may be counterproductive for effective anti-tumor immunity. Since
      Stat6-deficient or "knockout" mice lack the signal transducer and activator of
      transcription-6 protein and are unable to transmit signals initiated by the type
      2 cytokines, IL-4 and IL-13, they have been studied to confirm the T(h)1 vs T(h)2
      paradigm. Using transplantable tumor cells that cause primary solid tumors and
      metastatic disease, as well as a spontaneous transgenic tumor model, multiple
      studies have demonstrated that Stat6(-/-) mice are able to reject or delay
      primary tumor growth, prevent recurrence of primary tumors, and/or reject
      established, spontaneous metastatic disease. Deletion of the Stat6 gene,
      therefore, provides significantly enhanced immunosurveillance. Comparable
      experiments with CD1-deficient mice, which lack NKT cells and hence are deficient
      for IL-13, give similar results and suggest that removal of NKT cells also
      enhances immunosurveillance. Because immunity is enhanced in the absence of Stat6
      or CD1, it has been hypothesized that these deletions result in the removal of an
      inhibitor that blocks constitutive immunosurveillance. Several mechanisms have
      been tested as potential inhibitors, including CD4(+)CD25(+) T regulatory cells,
      IL-13, a T(h)2 shift, and myeloid suppressor cells. Although the first three
      mechanisms do not appear to be relevant, regression of myeloid suppressor cells
      in Stat6-deficient and CD1-deficient mice may be responsible for enhanced
      immunosurveillance. Although additional studies are clearly needed to clarify the
      mechanism(s) underlying improved anti-tumor immunity in Stat6(-/-) and CD1(-/-)
      mice, deletion of these genes results in a potent anti-tumor immunity and may be
      a basis for an immunotherapy strategy.

PMID- 14593500
TI  - The kinetic basis of glomerular filtration rate measurement and new concepts of
      indexation to body size.
AB  - As measurement of glomerular filtration rate (GFR) is now generally the
      responsibility of departments of nuclear medicine, it is important for nuclear
      medicine physicians and scientists to understand the pharmacokinetics of the
      indicators and radiotracers that are used, generally known as filtration markers.
      The single-injection, non-steady state technique is almost universally used,
      departments varying in how many blood samples are taken: rarely multisample
      clearance, which does not assume a single compartment of tracer distribution,
      commonly clearance based on a limited number of blood samples between 2 and 4 h
      after injection, which assumes a single compartment of distribution, and often a
      single sample at a defined time point. The volume of distribution, V(d), of a
      filtration marker is close to extracellular fluid volume (ECFV). GFR and ECFV are
      both overestimated by the assumption of a single compartment by amounts that are
      functions of the rate of plasma clearance, Z. Residence time, T, of tracer in its
      V(d) is equal to V(d) divided by Z. Z and T can both be measured from a
      multisample clearance curve, whereupon V(d) is the product of Z and T. GFR is
      usually indexed to patient size by expressing it in relation to body surface area
      (BSA), which in turn is calculated from an equation based on the patient's height
      and weight. An equation in common use was described by Haycock et al. and is
      BSA=0.024265 x weight(0.5378) x height(0.3964). An alternative indexation
      variable is ECFV. GFR per unit ECFV is close to the rate constant, alpha(3), of
      the terminal exponential of the plasma clearance curve. It is in fact slightly
      higher than this rate constant by an amount that is a function of the rate
      constant itself. The discrepancy between GFR/ECFV and alpha(3) arises from the
      development of a concentration gradient between interstitial fluid and plasma,
      which in turn produces an extrarenal veno-arterial gradient throughout the body.
      Indexing GFR to ECFV not only has physiological attractions (especially in
      children) but is technically simple because it requires measurement only of
      alpha(3) (slope-only technique). A disadvantage, however, is a lack of robustness
      in comparison with the conventional slope/intercept method, which measures tracer
      dilution as well as alpha(3). Nevertheless, the advantages of indexation to ECFV
      can still be exploited by changing the constants of an equation of the Haycock
      type so that the equation becomes a predictor of ECFV rather than BSA. A recently
      described equation is ECFV=0.02154 x weight(0.6469) x height(0.7236). Indexation
      to ECFV abolishes differences that arise between children and adults when GFR is
      indexed to BSA.

PMID- 14593504
TI  - Lincomycin, cultivation of producing strains and biosynthesis.
AB  - Lincomycin and its derivatives are antibiotics exhibiting biological activity
      against Gram-positive bacteria. The semi-synthetic chlorinated lincomycin
      derivative is used in clinical practice. The chemical structure of lincosamide
      antibiotics, cultivation of producing strains and analytical procedures used for
      separation and isolation of these compounds are described in this review.
      Biosynthesis of lincomycin and related compounds and its genetic control are
      briefly discussed.

PMID- 14593503
TI  - Plexiform schwannoma of the forearm.
AB  - We report a case of plexiform schwannoma located in the flexor muscles of the
      forearm in the absence of other signs of neurofibromatosis or schwannomatosis.
      Magnetic resonance examination revealed a multinodular irregular inhomogeneous
      mass. Some nodules displayed a peripheral, high intensity rim and a central low
      intensity (target sign) on T2-weighted images. Pre-operative diagnosis of the
      rare plexiform schwannoma may be possible with careful imaging examination for
      the target sign.

PMID- 14593505
TI  - Artificial carrier for oxygen supply in biological systems.
AB  - Several poly (dimethylsiloxanes) (PDMS) copolymers of dimethylsiloxane (DMS) with
      ethylene or propylene oxide were tested as artificial carriers for the delivery
      of oxygen to biological systems. Copolymers with a DMS content of 33% or lower
      enhanced glucose oxidation by 200% in contrast to the 25% increase produced by
      the same concentration of perfluorodecalin. When 0.05% of the copolymer with 18%
      DMS was included in the growth media of Bacillus thuriginensis, the biomass
      (growth rate) increased 1.5-fold. With 0.1% of this copolymer, actinorhodin
      production by Streptomyces coelicolor A3 (2) occurred in half the normal time and
      with an increased yield. In conclusion, these PDMS copolymers are a good
      alternative to perfluorodecalin as oxygen carriers in biotechnological processes.

PMID- 14593506
TI  - A screening system for antioxidants using thioredoxin-deficient yeast: discovery
      of thermostable antioxidant activity from Agaricus blazei Murill.
AB  - Previously, we found that cytosolic thioredoxin is a negative regulator for an
      oxidative stress responsive transcription factor, Yap1p (yeast AP-1-like
      transcription factor), i.e., this transcription factor is constitutively
      concentrated in the nucleus in the thioredoxin-deficient mutant ( trx1delta
      trx2delta) due to an impairment of the reactive oxygen species-scavenging
      activity of this mutant [Izawa et al. (1999) J Biol Chem 274:28459-28465]. Based
      on these findings, we developed a screening method to discover substances that
      show antioxidant activity. With this method, antioxidant activity was evaluated
      by monitoring the subcellular localization of Yap1p. Since Yap1p is oxidized and
      accumulates in the nucleus in trx1delta trx2Delta cells, it is easy to identify
      antioxidant activity by observing the localization of green fluorescent protein
      (GFP)-tagged Yap1p. If exogenous substances taken in by trx1delta trx2Delta cells
      were able to function as antioxidants to reduce the oxidized form of Yap1p, GFP1
      Yap1p would diffuse into the cytoplasm. We used this system to screen for
      antioxidant activity in mushrooms, and found that the edible mushroom Agaricus
      blazei Murill is an excellent source of antioxidants.

PMID- 14593507
TI  - Identification and functional characterization of a type I signal peptidase gene
      of Bacillus megaterium DSM319.
AB  - The sipM gene of Bacillus megaterium encoding a type I signal peptidase (SPase)
      was isolated and structurally characterized. RNA analysis revealed a transcript
      size in accordance with a bicistronic operon comprising sipM and an adjacent open
      reading frame. Inactivation of sipM by targeted gene disruption could not be
      achieved, indicating its essential role for cell viability since there might be
      no other type I SPase of major importance present in B. megaterium. Plasmid
      assisted amplification of the gene resulted in an increase in activity of the
      heterologous glucanase used as an extracellular reporter, suggesting a potential
      bottleneck for protein secretion within this species.

PMID- 14593508
TI  - Diglucosyl-glycerolipids from the marine sponge-associated Bacillus pumilus
      strain AAS3: their production, enzymatic modification and properties.
AB  - The marine strain Bacillus pumilus strain AAS3, isolated from the Mediterranean
      sponge Acanthella acuta, produced a diglucosyl-glycerolipid, 1,2-O-diacyl-3-[beta
      glucopyranosyl-(1-6)-beta-glucopyranosyl)]glycerol, with 14-methylhexadecanoic
      acid and 12-methyltetradecanoic acid as the main fatty acid moieties (GGL11). On
      a 30 l scale, using artificial seawater supplemented with glucose (20 g/l), yeast
      extract (10 g/l), and suitable nitrogen/phosphate sources, growth-associated
      glycoglycerolipid production reached its maximum yield of 90 mg/l after 11 h.
      Lipase-catalyzed modification of the native substance led to the deacylated
      parent compound (GG11), which could be reacylated using the same enzyme system to
      afford a new dipentenoyl-diglucosylglycerol (GGL12) as the major product upon
      addition of 4-pentenoic acid to the medium. GGL11 decreased the surface tension
      of water from 72 mN/m to 29 mN/m and the interfacial tension of the water/ n
      hexadecane system from 44 to 5 mN/m. Anti-tumor-promoting studies on this class
      of diglucosyl glycerol products showed that the carbohydrate/glycerol backbone
      (GG11) has a more potent inhibitory activity than the acylated compounds. The
      diglucosyl-glycerol GG11 strongly inhibited growth of the tumor cell lines HM02
      and Hep G2 (50% inhibition at approximately 1 microg/ml), while the glycerolipids
      GGL11 and GGL12 were less active or had no effect.

PMID- 14593509
TI  - Production of L-asparaginase in Enterobacter aerogenes expressing Vitreoscilla
      hemoglobin for efficient oxygen uptake.
AB  - This study is the first utilizing Vitreoscilla hemoglobin in a heterologous
      bacterium, Enterobacter aerogenes, to determine the effect of such a highly
      efficient oxygen-uptake system on the production of l-asparaginase, an enzyme
      that has attracted considerable attention due to its anti-tumor activity. Here,
      we show that the Vitreoscilla hemoglobin expressing strain has from 10-fold to
      more than two orders of magnitude lower l-asparaginase activity than the wild
      type or the control without the Vitreoscilla hemoglobin gene under different
      aeration conditions. Aeration and agitation were also determining factors for
      enzyme production. The enzyme activity was reduced considerably under both full
      aerobic and anaerobic conditions, while the highest enzyme activity was
      determined in cultures under low aeration and low agitation. Also, the effect of
      different concentrations of glucose on enzyme production showed catabolic
      repression. Glucose at 1% caused almost total inhibition of enzyme activity,
      while at 0.1% it showed a slightly stimulatory effect on enzyme production,
      compared with glucose-free medium.

PMID- 14593510
TI  - Gene cloning and overexpression of two conjugated polyketone reductases, novel
      aldo-keto reductase family enzymes, of Candida parapsilosis.
AB  - The genes encoding two conjugated polyketone reductases (CPR-C1, CPR-C2) of
      Candida parapsilosis IFO 0708 were cloned and sequenced. The genes encoded a
      total of 304 and 307 amino acid residues for CPR-C1 and CPR-C2, respectively. The
      deduced amino acid sequences of the two enzymes showed high similarity to each
      other and to several proteins of the aldo-keto reductase (AKR) superfamily.
      However, several amino acid residues in putative active sites of AKRs were not
      conserved in CPR-C1 and CPR-C2. The two CPR genes were overexpressed in
      Escherichia coli. The E. coli transformant bearing the CPR-C2 gene almost
      stoichiometrically reduced 30 mg ketopantoyl lactone/ml to D-pantoyl lactone.

PMID- 14593514
TI  - Controlled E-field gradient coils.
AB  - Peripheral neural stimulation is a major problem in current gradient coil
      designs. Induced current problems in patients relate directly to gradient
      strength and modulation frequency. Current designs of gradient coil tend to limit
      ultra-high-speed imaging methods such as echo-planar imaging through the effect
      of induced currents which produce tingling sensations and involuntary muscle
      twitch. Neural stimulation could also trigger epileptic fits and/or cardiac
      fibrillation. For reduction of induced currents, an important aspect is the coil
      geometry. It is desirable to design the gradient coil in such a way as to prevent
      closed loop circulating currents within the body. Preliminary results using a
      four-sector gradient coil with rectangular geometry, operating in a low mutual
      coupling mode, indicate significant reduction in the E-field within the subject
      volume of the coil. Reduction in induced currents in the patient allows safer
      operation at higher magnetic field strengths together with faster scans currently
      prohibited through neural stimulation effects in standard coil geometries.

PMID- 14593511
TI  - Influence of the whole-cell patch-clamp configuration on electrophysiological
      properties of the voltage-dependent sodium current expressed in MDA-MB-231 breast
      cancer cells.
AB  - Voltage-gated ionic channels are known to be involved in oncogenesis. However,
      only a few studies describe the functional characteristics of these channels or
      the mechanisms by which they are involved in the proliferation and invasive
      processes. Breast cancer cells proliferate and migrate under the constant
      activation of growth factors, hormones, extracellular matrix interactions, etc.
      It would thus not be surprising if the activity of the ionic channels was
      modulated by intracellular regulation pathways such as kinases or phosphatases,
      which in turn can affect oncogenic properties. In the present study, we
      investigated some of the electrophysiological properties of the fast inward
      sodium current found in the breast cancer cell line MDA-MB-231 with two
      configurations of the patch-clamp technique. With perforated patch, a
      configuration which allows to keep the cytoplam intact, the mean current
      amplitude was lower, the relative conductance-voltage relationship was shifted to
      more positive potentials and the recovery from inactivation was accelerated when
      compared to ruptured patch, where the cytoplasm is dialysed by the intrapipette
      solution. There was no difference in availability-voltage (pseudo-steady-state
      inactivation) relationship and in time to peak of the current. These results
      suggest that regulation mechanisms, possibly involving kinases or phosphatases,
      are switched off when the cytoplasm is diluted. We propose that such a regulation
      can modulate the functioning of the channels even in the absence of membrane
      voltage changes, which in turn can affect oncogenic properties. This finding is
      of importance when evaluating the physiopathological role of ionic channel in
      cancer development.

PMID- 14593515
TI  - Seasonal changes in general activity, body mass and reproduction of two small
      nocturnal primates: a comparison of the golden brown mouse lemur ( Microcebus
      ravelobensis) in Northwestern Madagascar and the brown mouse lemur ( Microcebus
      rufus) in Eastern Madagascar.
AB  - To investigate for the first time the relationship between contrasting patterns
      of seasonal changes of the environment and activity, body mass and reproduction
      for small nocturnal primates in nature, we compared a population of golden brown
      mouse lemur ( Microcebus ravelobensis) in a dry deciduous forest of northwestern
      Madagascar and of the brown mouse lemur ( Microcebus rufus) in an evergreen rain
      forest of eastern Madagascar. Both species live under similar photoperiodic
      conditions. Golden brown mouse lemurs (GBML) were active during the whole period
      (May to December) irrespective of changing environmental conditions. In contrast,
      a part of the population of brown mouse lemurs (BML) showed prolonged seasonal
      torpor, related to body mass during periods of short day length and low ambient
      temperatures. Differences between species might be due to differences in ambient
      temperature and food supply. Body weight and tail thickness (adipose tissue
      reserve) did not show prominent differences between short and long photoperiods
      in GBML, whereas both differ significantly in BML, suggesting species-specific
      differences in the photoperiodically driven control of metabolism. Both species
      showed a seasonal reproduction. The rate of growth and size of the testes were
      similar and preceded estrous onset in both species suggesting a photoperiodic
      control of reproduction in males. The estrous onset in females occurred earlier
      in GBML than in BML. Estrous females were observed over at least 4 months in the
      former, but in only 1 month in the latter species. Intraspecific variation of
      estrous onset in GBML may be explained by body mass. Interspecific variation of
      female reproduction indicates species-specific differences in the control of
      reproduction. Thus, environmentally related differences in annual rhythms between
      closely related small nocturnal lemurs emerged that allow them to cope with
      contrasting patterns of seasonal changes in their habitats.

PMID- 14593516
TI  - Colour discrimination learning in black-handed tamarin ( Saguinus midas niger).
AB  - Colour is one cue that monkeys use for perceptual segregation of targets and to
      identify food resources. For fruit-eating primates such as Saguinus, an accurate
      colour perception would be advantageous to help find ripe fruits at distance. The
      colour vision abilities of black-handed tamarins ( Saguinus midas niger) were
      assessed through a discrimination learning paradigm using Munsell colour chips as
      stimuli. Pairs of chips were chosen from an early experiment with protan and
      deutan humans. The monkeys (three males and one female) were tested with stimuli
      of the same hue, but different brightness values, in order to make sure that
      discriminations were based on colour rather than brightness cues. The results
      showed that the female, but not the males, presented an above-chance performance
      for stimuli resembling hue conditions under which tamarins forage (oranges vs
      greens). Colour vision in S. m. niger is discussed according to the advantages
      and disadvantages of dichromatism in daily search for food as well as to aspects
      regarding polymorphism in New World monkeys.

PMID- 14593517
TI  - Atypical morphology of dark septate fungal root endophytes of Bouteloua in arid
      southwestern USA rangelands.
AB  - Native grasses of semi-arid rangelands of the southwestern USA are more
      extensively colonized by dark septate endophytes (DSE) than by traditional
      mycorrhizal fungi. Roots of dominant grasses ( Bouteloua sp.) native to arid
      southwestern USA rangelands were prepared and stained using stains specific for
      fungi (trypan blue) and for lipids (sudan IV). This revealed extensive internal
      colonization of physiologically active roots by atypical fungal structures that
      appear to function as protoplasts, without a distinguishable wall or with very
      thin hyaline walls that escape detection by methods staining specifically for
      fungal chitin. These structures were presumed to be active fungal stages that
      progressed to form stained or melanized septate hyphae and microsclerotia
      characteristic of DSE fungi within dormant roots. The most conspicuous
      characteristic of these fungi were the unique associations that formed within
      sieve elements and the accumulation of massive quantities of lipids. This
      interface suggests a biologically significant location for carbon transfer
      between the plant and fungus. The continuous intimate association with all sieve
      elements, cortical and epidermal cells as well as external extension on the root
      surface and into the soil indicates that they are systemic and considerably more
      prevalent than previously thought. A fungal network associated with a
      mucilaginous complex observed on the root surface and its potential role in root
      function in dry soil is discussed. It is suggested that those fungi that non
      pathogenically and totally colonize plant cells be classed as systemic endophytic
      fungi (SEF). This would refine the broad designation of DSE fungi. The potential
      mutualistic benefit of SEF for native plants in arid ecosystems based on the
      extent of lipid accumulation and its apparent distribution is discussed.

PMID- 14593518
TI  - Influence of a Bacillus sp. on physiological activities of two arbuscular
      mycorrhizal fungi and on plant responses to PEG-induced drought stress.
AB  - The effects of bacterial inoculation (Bacillus sp.) on the development and
      physiology of the symbiosis between lettuce and the arbuscular mycorrhizal (AM)
      fungi Glomus mosseae (Nicol. and Gerd.) Gerd. and Trappe and Glomus intraradices
      (Schenck and Smith) were investigated. Plant growth, mineral nutrition and gas
      exchange values in response to bacterial inoculation after PEG-induced drought
      stress were also evaluated. In AM plants, inoculation with Bacillus sp. enhanced
      fungal development and metabolism, measured as succinate dehydrogenase (SDH) and
      alkaline phosphatase (ALP) activities, more than plant growth. Under non-stressed
      conditions, G. intraradices colonization increased all plant physiological values
      to a higher extent when in dual inoculation with the bacterium. Under stress
      conditions, the bacterium had an important stimulatory effect on G. intraradices
      development. Under such conditions, the effects of the bacterium on
      photosynthetic rate, water use efficiency (WUE) and stomatal conductance of
      lettuce plants differed with the fungus species. Plant-gas exchange was enhanced
      in G. intraradices- and reduced in G. mosseae-colonized plants when co-inoculated
      with Bacillus sp. Thus, the effects of each fungus on plant physiology were
      modulated by the bacterium. Stress was detrimental, particularly in G.
      intraradices-colonized plants without the bacterium, reducing intra and
      extraradical mycelium growth and vitality (SDH), as well as plant-gas exchange.
      Nevertheless, Bacillus sp. inoculation improved all these plant and fungal
      parameters to the same level as in non-stressed plants. The highest amount of
      alive and active AM mycelium for both fungi was obtained after co-inoculation
      with Bacillus sp. These results suggest that selected free-living bacteria and AM
      fungi should be co-inoculated to optimize the formation and functioning of the AM
      symbiosis in both normal and adverse environments.

PMID- 14593519
TI  - Epiphytic and terrestrial mycorrhizas in a lower montane Costa Rican cloud
      forest.
AB  - The epiphyte community is the most diverse plant community in neotropical cloud
      forests and its collective biomass can exceed that of the terrestrial shrubs and
      herbs. However, little is known about the role of mycorrhizas in this community.
      We assessed the mycorrhizal status of epiphytic (Araceae, Clusiaceae, Ericaceae,
      and Piperaceae) and terrestrial (Clusiaceae, Ericaceae) plants in a lower montane
      cloud forest in Costa Rica. Arbuscular mycorrhizas were observed in taxa from
      Araceae and Clusiaceae; ericoid mycorrhizas were observed in ericaceous plants.
      This is the first report of intracellular hyphal coils characteristic of ericoid
      mycorrhizas in roots of Cavendishia melastomoides, Disterigma humboldtii, and
      Gaultheria erecta. Ericaceous roots were also covered by an intermittent hyphal
      mantle that penetrated between epidermal cells. Mantles, observed uniquely on
      ericaceous roots, were more abundant on terrestrial than on epiphytic roots.
      Mantle abundance was negatively correlated with gravimetric soil water content
      for epiphytic samples. Dark septate endophytic (DSE) fungi colonized roots of all
      four families. For the common epiphyte D. humboldtii, DSE structures were most
      abundant on samples collected from exposed microsites in the canopy. The presence
      of mycorrhizas in all epiphytes except Peperomia sp. suggests that inoculum
      levels and environmental conditions in the canopy of tropical cloud forests are
      generally conducive to the formation of mycorrhizas. These may impact nutrient
      and water dynamics in arboreal ecosystems.

PMID- 14593520
TI  - Genetic diversity of an ectomycorrhizal fungus Tricholoma terreum in a Larix
      principis-rupprechtii stand assessed using random amplified polymorphic DNA.
AB  - The genetic variation and spatial distribution of the ectomycorrhizal fungus
      Tricholoma terreum was studied in an artificial Larix principis-rupprechtii stand
      in China. The 33 sporophores studied belonged to distinct genotypes, based on
      analysis of random amplified polymorphic DNA (RAPD) markers. The genets of T.
      terreum were small and no larger than 0.5 m. Two major phenetic groups, i.e.
      eight individuals in group 1 and 25 in group 2, were identified by principal
      component analysis and the unweighted pair group method with arithmetic means of
      simple matching coefficients, respectively. The genetic diversity as determined
      by the Shannon-Weaver diversity index was 4.52 for these 33 sporophores.
      Furthermore, there was a slightly lower diversity index in group 1 (4.28) than in
      group 2 (4.46). It is suggested that sexual spore propagation is very important
      in the life history of T. terreum in this larch forest.

PMID- 14593521
TI  - Perceptions of upper-body problems during recovery from breast cancer treatment.
AB  - Despite improved recognition recently, restrictions in upper-body movement
      continue to cause impairment and distress for many women long after breast cancer
      treatment. The purpose of this research is to investigate this issue through the
      perceptions of breast cancer survivors in the context of their everyday lives.
      Twenty-four women recruited from a private breast clinic in south-eastern
      Queensland, Australia, participated in a qualitative study. Discussion groups
      comprised women treated for breast cancer within the previous 18 months.
      Discussions centred on experiences of physical difficulties, follow-up support,
      arm lymphoedema and exercise therapy during the women's recoveries. Returning to
      normal activities for women after breast surgery was felt to take longer than
      either the women's or their physicians' expectations. Many women reported
      difficulties in upper-body tasks, which worsened simple everyday
      responsibilities. The physical impact leads to psychological strain, as the women
      are constantly reminded of their illness and the possibility they may never
      return to their full capacity. These upper-body difficulties may include
      discomfort while driving and sleeping, posture disturbances, reduced
      employability in physical work, and decreased ability to do housework and
      gardening. Having lymphoedema or the threat of developing it was very distressing
      for most women. The potential preventive role of physiotherapy-led exercises to
      prevent further decline and improve function was strongly emphasised during these
      discussions. Clinicians need to recognise that it is very common for women with
      breast cancer to experience upper-body morbidity long after their treatment, and
      consequently every effort to enhance recovery and avoid further deterioration in
      function is required.

PMID- 14593523
TI  - Implication of serum IgE in childhood nephrotic syndrome.
AB  - Elevated serum IgE levels have been related to glomerular diseases. We
      investigated the relationship between serum total and specific IgE levels and
      their modulating factors [interleukin-4 (IL-4) and sCD23] and the outcome of
      childhood nephrotic syndrome (NS) after steroid treatment. We found that children
      with NS had significantly higher serum IgE levels than age-matched allergic
      patients and normal controls. Patients with steroid-resistant nephrotic syndrome
      (SRNS) had higher serum IgE levels than patients with steroid-sensitive nephrotic
      syndrome (SSNS) both pre and post treatment. Elevated initial serum IgE levels
      appeared to be associated with poor outcome. Although one-half of nephrotic
      children had detectable specific IgE to common allergens (dust mites or milk),
      the presence of specific IgE was not correlated with disease outcome. Serum IL-4
      levels were not different among normal controls and patients with SRNS or SSNS.
      However, serum sCD23 levels in NS patients were significantly higher than in
      normal controls both pre and post treatment. Serum sCD23, but not IL-4, levels
      were correlated with serum total IgE levels. Our results suggest that regulation
      of total IgE production correlates with the disease activity and outcome of NS,
      although the presence of common specific IgE may not be linked to the
      pathogenesis.

PMID- 14593522
TI  - Risk factors for poor renal prognosis in children with hemolytic uremic syndrome.
AB  - Many factors have been proposed as predictors of poor renal prognosis in children
      with hemolytic uremic syndrome (HUS), but their role is still controversial. Our
      aim was to detect the most reliable early predictors of poor renal prognosis to
      promptly identify children at major risk of bad outcome who could eventually
      benefit from early specific treatments, such as plasmapheresis. Prognostic
      factors identifiable at onset of HUS were evaluated by survival analysis and a
      proportional hazard model. These included age at onset, prodromal diarrhea (D),
      leukocyte count, central nervous system (CNS) involvement, and evidence of Shiga
      toxin-producing Escherichia coli (STEC) infection. Three hundred and eighty-seven
      HUS cases were reported; 276 were investigated for STEC infection and 189 (68%)
      proved positive. Age at onset, leukocyte count, and CNS involvement were not
      associated with the time to recovery. Absence of prodromal D and lack of evidence
      of STEC infection were independently associated with a poor renal prognosis; only
      34% of patients D(-)STEC(- )recovered normal renal function compared with 65%-76%
      of D(+)STEC(+), D(+)STEC(-) and D(-)STEC(+ )patients. In conclusion, absence of
      both D and evidence of STEC infection are needed to identify patients with HUS
      and worst prognosis, while D(-) but STEC(+) patients have a significantly better
      prognosis.

PMID- 14593524
TI  - Mothers influence offspring body size through post-oviposition maternal effects
      in the redbacked salamander, Plethodon cinereus.
AB  - In the terrestrial salamander (Plethodon cinereus), previous work has shown that
      mother's body size is positively correlated to offspring size at the time of
      hatching even after controlling for the effects of egg size. This study was
      designed to determine whether maternal body size affects offspring size via pre
      oviposition factors (e.g., yolk quality, jelly coat composition, or maternal
      genes) or post-oviposition factors (e.g., parental care behaviors, parental
      modification of environment). Gravid females were captured and induced to lay
      eggs in experimental chambers in which the environment was standardized. Fifteen
      clutches were exchanged, or cross-fostered, between female pairs differing in
      body size. Ten females whose eggs were taken away and then returned served as
      controls for the crossing treatment. Foster mothers did not significantly differ
      from control mothers in the time spent with eggs, body position, or number of egg
      movements during brooding. Average egg mass measured midway through development
      was not significantly correlated to the body size of either the genetic or foster
      mother, but was correlated to pre-oviposition oocyte size. At hatching, offspring
      body length was positively correlated to egg size and the foster mother's body
      size. This correlation suggests that in P. cinereus post-oviposition maternal
      effects have a greater impact on offspring size than other maternal factors
      incorporated into the egg prior to oviposition. While our study showed that
      larger mothers moved their eggs less often and tended to spend more time in
      contact with their eggs, further work needs to be done to identify the specific
      mechanisms through which larger mothers influence the body size of their
      offspring. This is the first experimental demonstration of post-oviposition
      maternal effects for any amphibian with parental care.

PMID- 14593525
TI  - Sulfur stable isotopes separate producers in marine food-web analysis.
AB  - Ecological applications of stable isotope analysis rely on different producers
      having distinct isotopic ratios to trace energy and nutrient transfer to
      consumers. Carbon (C) and nitrogen (N) are the usual elements analysed. We tested
      the hypothesis that producers unable to be separated using C and N would be
      separated by sulphur (S), by reviewing estuarine and marine food web studies
      using all three elements (total of 836 pairwise comparisons between producers). S
      had a wider range of values across all producers than C and N (S: 34.4, C: 23.3,
      N: 18.7 per thousand ), and a higher mean difference among producers (S: 9.3, C:
      6.5, N: 3.3 per thousand ). We varied from 1 to 10 per thousand the distance
      producers must be apart to be considered separate. For each of these gap
      distances, S-separated producers tied on C and N in 40% or more of cases.
      Comparing the three elements individually, S had fewer tied pairs of producers
      for any gap distance than C or N. However, S also has higher within-producer
      variability. Statistical tests on simulated data showed that this higher
      variability caused S to be less effective than C for analysing differences among
      mean producer values, yet mixing models showed that S had the smallest confidence
      intervals around mean estimates of source contributions to consumers. We also
      examined the spatial and temporal scales over which S isotope signatures of the
      saltmarsh plant Spartina alterniflora varied. Differences between samples taken
      within tens of metres were smallest, but between samples hundreds of metres apart
      were as different as samples thousands of kilometres apart. The time between
      samples being taken did not influence S signatures. Overall, the use of S is
      recommended because it has a high probability of distinguishing the contribution
      of different producers to aquatic food webs. When two elements are employed, the
      combination of S and C separates more producers than any other combination.

PMID- 14593526
TI  - How prevalent is crassulacean acid metabolism among vascular epiphytes?
AB  - The occurrence of crassulacean acid metabolism (CAM) in the epiphyte community of
      a lowland forest of the Atlantic slope of Panama was investigated. I hypothesized
      that CAM is mostly found in orchids, of which many species are relatively small
      and/or rare. Thus, the relative proportion of species with CAM should not be a
      good indicator for the prevalence of this photosynthetic pathway in a community
      when expressed on an individual or a biomass basis. In 0.4 ha of forest, 103
      species of vascular epiphytes with 13,099 individuals were found. As judged from
      the C isotope ratios and the absence of Kranz anatomy, CAM was detected in 20
      species (19.4% of the total), which were members of the families Orchidaceae,
      Bromeliaceae, and Cactaceae. As predicted, the contribution of CAM epiphytes to
      the total number of individuals and to total biomass (69.6 kg ha(-1)) was
      considerably lower (3.6% or 466 individuals and, respectively, 3.0% or 2.1 kg ha(
      1)).

PMID- 14593527
TI  - Moisture conditions and the presence of bryophytes determine fescue species
      abundance in a dry calcareous grassland.
AB  - Festuca ovina is the abundant matrix-forming species and F. rubra a subordinate
      species in shallow-soil calcareous grasslands. F. pratensis is a transient
      species, occurring sparsely in this community. We hypothesised that the different
      abundances of these three species are primarily due to the differential effect of
      moisture conditions on their germination and early establishment, and that the
      effect of the pattern of rainfall intensity depends on the presence or absence of
      a bryophyte layer. We studied the dependence of the germination and establishment
      of the three fescue species on the moisture conditions both in the laboratory and
      in the patches of intact grassland community (microcosms). In a laboratory
      germination experiment, F. pratensis showed the highest, F. rubra, the
      intermediate and F. ovina, the lowest drought tolerance. In microcosms, the
      establishment of F. ovina was the highest. At the same time, the annual mortality
      of seedlings of F. ovina was the lowest. All three species responded positively
      to an increasing irrigation level. Differently from F. ovina, F. rubra showed a
      positive response only in plots from which the bryophyte layer had been removed,
      while F. pratensis responded positively to both irrigation and bryophyte removal.
      We conclude that moisture conditions have a differential effect on the three
      fescue species mainly in the seedling establishment, not in the germination
      phase. For the successful establishment of F. rubra and F. pratensis, the
      coincidence of high rainfall and local disturbance, removing bryophytes, is
      required. The presence or absence of bryophytes had no effect on establishment in
      dry years, while in rainy years the removal of bryophytes has a clear positive
      effect.

PMID- 14593528
TI  - Subfamily III of mammalian oxysterol-binding protein (OSBP) homologues: the
      expression and intracellular localization of ORP3, ORP6, and ORP7.
AB  - The human OSBP related protein (ORP) family consists of 12 members, which can be
      divided into six subfamilies based on the genomic organization and amino acid
      homology. Here we performed basic characterization of subfamily III, which
      consists of three members: ORP3, ORP6, and ORP7. According to cDNA hybridization,
      the three genes are expressed in a tissue-specific manner. While ORP3 mRNA is
      most abundant in kidney, lymph nodes, and thymus, ORP6 shows highest expression
      in brain and skeletal muscle, and ORP7 in the gastrointestinal tract. Using
      monospecific peptide antibodies, we confirmed the presence of the three proteins
      in human and mouse tissues. ORP6 gene expression was induced upon differentiation
      of F9 embryonic carcinoma cells into parietal endoderm, while ORP3 and ORP7 mRNA
      levels were unchanged. In the F9 cells, endogenous ORP6 associated predominantly
      with the nuclear envelope. When expressed from the cDNA in cultured cells, the
      three proteins were distributed between the cytosol and endoplasmic reticulum
      (ER) membranes, with a minor portion found at the plasma membrane. Experiments
      with truncated constructs showed that the N-terminal portion of the proteins,
      containing a pleckstrin homology (PH) domain, has markedly strong plasma membrane
      targeting specificity, while the C-terminal half remains largely cytosolic. The
      expression data demonstrates that ORP3, -6, and -7 are not merely redundant gene
      products but show marked quantitative differences in tissue expression,
      suggesting tissue-specific aspects in their function. The dual targeting of the
      proteins indicates a putative role in communication between the ER and the plasma
      membrane.

PMID- 14593529
TI  - The impact of factor XIIIa V34L polymorphism on plasma factor XIII activity in
      the Chinese and Asian Indians from Singapore.
AB  - Factor XIII (FXIII) is a plasma transglutaminase that is essential for normal
      haemostasis and fibrinolysis. A few polymorphic sites have been identified in the
      gene, one of them being a point mutation (V34L) in exon 2 of the FXIIIa subunit
      gene leading to an amino acid change of valine to leucine. We have examined the
      role of this polymorphism in relation to plasma FXIII activity in a total of 532
      healthy individuals belonging to two ethnic groups in Singapore. The frequency of
      the L34 allele was significantly higher ( P<0.001) among the Asian Indians (0.08)
      when compared with the Chinese (0.005). No significant difference in frequency of
      the L34 allele was observed between Asian Indian CAD patients and controls. The
      mean FXIII levels were significantly higher ( P<0.0005) among the Asian Indians
      (148.4%+/-35.5) when compared with Chinese (111.2%+/-26.7). The L34 variant was
      associated with increased FXIII activity among Asian Indian females. This study
      shows that both racial and genetic components play a significant role in
      determining plasma FXIII activity. The effect of V34L polymorphism on FXIII
      activity in the Indian females is independent of the effects of the P564L and
      E651Q polymorphic sites in the FXIIIa gene.

PMID- 14593530
TI  - Effects of intraperitoneal administration of gemcitabine and paclitaxel on
      hepatic regeneration in rats.
AB  - BACKGROUND/AIMS: We aimed to test clinical implications of intra-peritoneally
      administered gemcitabine and paclitaxel on hepatic regeneration after hepatic
      resection in rats. METHODS: Fifty male, Swiss albino rats weighing between 200
      and 240 g were used. After a 30% partial hepatectomy was performed (except Sham
      group), animals were divided into five groups as: high-dose gemcitabine, low-dose
      gemcitabine, paclitaxel, control, and Sham operation groups. In the high-dose and
      low-dose gemcitabine groups, animals received 200 and 12.5 mg/kg intraperitoneal
      gemcitabine for five days after partial hepatectomy respectively. In the
      paclitaxel group, animals were administered 6 mg/kg paclitaxel in the same
      fashion. Control and Sham groups received intraperitoneal 0.9% NaCl. On the sixth
      postoperative day, the animals were killed liver tissues were resected,
      proliferating cell nuclear antigen immunopositivity was determined and weight
      loss and diarrhea were assessed. RESULTS: Gemcitabine and paclitaxel treated
      animals lost weight and had more severe diarrhea than control and Sham group
      animals. No significant difference was observed between treatment groups in terms
      of weight loss, diarrhea, and proliferating cell nuclear antigen. When treatment
      groups were compared to the control group in terms of proliferating cell nuclear
      antigen immunopositivity, no significant differences were detected. CONCLUSIONS:
      It can be concluded that adjuvant chemotherapy with gemcitabine and paclitaxel is
      a safe option in terms of liver regeneration and side effects such as diarrhea
      and weight loss.

PMID- 14593531
TI  - Serum profile of T helper 1 and T helper 2 cytokines in patients with chronic
      hepatitis C virus infection.
AB  - BACKGROUND/AIMS: T cell immunoregulatory cytokines may play a crucial role in the
      host response to hepatitis C virus infection. While T-helper type 1 cytokines are
      required for host antiviral immune responses, T-helper type 2 cytokines can
      inhibit the development of these effector mechanisms. The aim of the present
      study was to determine T-helper type 1 and T-helper type 2 cytokine levels in
      chronic hepatitis C infection. METHODS: Serum levels of T-helper type 1 cytokine,
      interferon-gamma (IFN-g), and T-helper type 2 cytokines, IL-4 and IL-10 were
      measured in 30 patients with hepatitis C infection and 25 healthy controls using
      ELISA. Serum levels of alanine transaminase were also assessed in both patients
      and controls. Histologic activity score was evaluated in the chronic hepatic C
      infected patients. RESULTS: Serum levels of IFN-g were 59.03+/-46.24 pg/mL, IL-4
      were 213.59+/-135.67 pg/mL and IL-10 were 106.73+/-60.85 pg/mL in hepatitis C
      infected patients whereas in healthy controls they were found to be 61.84+/-54.87
      pg/mL, 67.39+/-59.74 pg/mL and 60.14+/-50.73 pg/mL respectively. Serum levels of
      IL-4, IL-10 but not IFN-g were found to be significantly increased in chronic HCV
      patients compared to those of control subjects. CONCLUSIONS: Our findings may
      suggest the involvement of Th2 cytokines in the pathogenesis of chronic hepatitis
      C virus liver disease.

PMID- 14593532
TI  - Serum levels of acute phase proteins in patients with nonalcoholic
      steatohepatitis.
AB  - BACKGROUND/AIMS: A simple and practical method of detecting the degree of the
      inflammatory response during the development of nonalcoholic steatohepatitis has
      not been developed to date. In this study the serum levels of acute phase
      proteins in patients with nonalcoholic steatohepatitis and whether these levels
      had any relationship with histopathological findings in the liver were evaluated.
      METHODS: The study included 18 patients with NASH diagnosed by liver biopsy (13
      males and five females with a mean age of 44 years) and 16 healthy volunteers as
      a control group (11 males and five females, with a mean age of 40 years). The
      serum levels of C-reactive protein, C-reactive ceruloplasmin, ferritin,
      transferrin, alpha-1-acid glycoprotein, alpha-2-macroglobulin, alpha-1
      antitripsin, albumin, haptoglobulin and lipoprotein (a) were determined by
      nephelometric method in both groups. In patients with nonalcoholic
      steatohepatitis, liver histopathology was assessed using a modified scoring
      system based on the classification defined by Brunt. RESULTS: Serum C-reactive,
      ferritin, alpha-2-macroglobulin and ceruloplasmin concentrations in patients with
      nonalcoholic steatohepatitis were significantly higher than those of the control
      group (p=0.0001, p=0.001, p=0.007, p=0.01 respectively), but serum transferrin,
      albumin, haptoglobin, alpha-1-acid glycoprotein, alpha-1-antitripsin and
      lipoprotein (a) levels were not different. There was no difference in C-reactive
      protein levels regarding the degree of hepatic steatosis and inflammation and the
      stage of liver fibrosis. Acute phase proteins had no correlation with liver
      histology. CONCLUSIONS: Measurement of serum C-reactive protein, ferritin,
      ceruloplasmin and alpha-2-macroglobulin levels may be useful in assessing
      patients at risk of nonalcoholic steatohepatitis and those with high C-reactive
      protein and ferritin but normal transferrin should be considered for liver
      biopsy.

PMID- 14593533
TI  - Short term effects of valsartan on portal blood flow in cirrhotic patients.
AB  - BACKGROUND/AIMS: Portal hypertension is a common syndrome characterized by a
      chronic increase of the portal pressure and is the most frequent clinical
      manifestation of cirrhosis. In this study short term effects of Valsartan, an
      angiotensin II receptor antagonist, upon portal blood flow in 36 cirrhotic
      patients was determined by Doppler ultrasonography. METHODS: Patients were
      divided into three groups of 12 according to Child-Pugh classification. They (18
      women and 18 men with a mean age of 50+/-14 years) received a daily dose of 80 mg
      valsartan for one week after which the effects upon hemodynamic changes were
      evaluated by colored Doppler ultrasonography. Hemodynamic measurements were
      performed 24 hours prior to valsartan administration and then four and eight days
      after adiministration. The following parameters were evaluated: for hemodynamic
      changes: peak systolic flow velocity, diastolic flow velocity, peak systolic flow
      velocity/diastolic flow velocity ratio, resistive index and pulsatility index
      were evaluated in hepatic, superior mesenteric and right and left renal arteries.
      In the portal vein, diameter, mean flow velocity and flow volume were evaluated.
      Results are expressed as means+/-SD. RESULTS: Hemodynamic parameters showed no
      significant change during the measurement in hepatic, superior and right and left
      renal arteries. Valsartan induced a significant decrease (p<0.05) in portal vein
      diameter, in portal vein maximal flow velocity and in portal vein flow volume.
      The decrease in portal vein flow volume was 11.7% on day four and 24.4% on day
      eight. In two patients, a symptomatic hypotensive attack occurred. Serum
      potassium levels were increased significantly (p<0.05). CONCLUSIONS: These
      results indicate that valsartan can be used in portal hypertension safely.

PMID- 14593534
TI  - The effects of alpha - tocopherol and verapamil on mucosal functions after gut
      ischemia / reperfusion.
AB  - BACKGROUND/AIMS: We have previously shown that in the canine small bowel
      autotransplantation model, adding alpha - tocopherol to Euro Collins solution for
      perfusion enhanced the integrity of the small bowel mucosa for up to 12 hours in
      the posttransplantation period. The purpose of this study was to investigate the
      effects of verapamil and a tocopherol on reperfusion injury in the canine small
      bowel autotransplantation model. METHODS: The study consisted of four groups of
      six animals each. In Group 1 (control group) grafts were perfused with Euro
      Collins solution while those of Group 2 were perfused with Euro Collins and alpha
      tocopherol. Group 3 grafts were perfused with Euro Collins + verapamil and Group
      4 with Euro Collins, alpha- tocopherol and verapamil. Autotransplantation model
      was used to avoid immunological injury. Graft function and mucosal integrity were
      assessed by the analysis of enzymatic activities (mucosal glutaminase, maltase
      and lactase) and histopathological examination. Malonyldialdehyde (per gram
      tissue) was used as an indicator of lipid peroxidation. RESULTS: Glutaminase
      activity of Group 4 was found to be higher than that of the other groups at all
      time points (p<0.05). In the verapamil group (Group 3), the amount of lipid
      peroxidation showed the greatest decrease in comparison to other groups at the 12
      hour time point (p<0.05). Maltase activity in Group 3 was significantly different
      at all time points (p<0.05). Lactase activity showed no significant difference
      between groups at each time point. The microscopic appearance of tissue injury
      shown by histopathological examination of tissue samples obtained at different
      time points was related to decrease in mucosal enzymatic activities. CONCLUSIONS:
      alpha- tocopherol is a promising agent for the prevention of tissue injury caused
      by free oxygen radicals during organ transplantation. Verapamil, as an
      antioxidant, also has preventive effects in organ preservation. Using verapamil
      together with alpha- tocopherol in the same preservation solution did not
      increase the preventive effect of alpha- tocopherol.

PMID- 14593535
TI  - The association of short segment Barrett's esophagus with intestinal metaplasia
      in stomach.
AB  - BACKGROUND/AIMS: The aims of this study were to investigate the presence of short
      segment Barrett's esophagus in people found to have tongue-like columnar mucosal
      protrusions in the distal esophagus and to determine the relationship between
      short segment Barrert's esophagus and Helicobacter pylori, gastritis and
      intestinal metaplasia observed in other parts of the stomach. METHODS: The study
      included 50 patients (32 male, 18 female). Two biopsy specimens were taken from
      the antrum, at least 2 cm away from the pylorus, from the incisura angularis,
      corpus and cardia and four biopsy specimens were taken from tongue-like columnar
      protrusions (<3 cm long) above the gastroesophageal junction. Tissue samples were
      stained with hematoxyline-eosine, HID-Alcian blue pH 2.5 and modified Giemsa.
      RESULTS: Of the 50 subjects who were found to have tongue-like columnar
      protrusions above the gastroesophageal junction, short segment Barrett's
      esophagus was detected in nine (18%). Whereas all short segment Barretti's
      esophagus cases were associated with chronic gastritis, Helicobacter pylori was
      found to be positive in five (55.5%) of them and there was intestinal metaplasia
      in other parts of the stomach (antrum in two patients, incisura angularis in
      three, antrum and cardia in one) in six (66.6%) cases. In 41 patients without
      short segment Barrett's esophagus 33 (80%) had chronic gastritis, 27 (66%) had
      Helicobacter pylori infection and eight had intestinal metaplasia in different
      locations (there in antrum, four in incisura angularis, one in the antrum and
      cardia) of the stomach. CONCLUSIONS: An association between short segment
      Barrett's esophagus and intestinal metaplasia was found in different parts of the
      stomach. The link between intestinal metaplasia in the stomach and these
      metaplastic changes in the tubular esophagus requires evalation in larger and
      more comprehensive studies.

PMID- 14593536
TI  - Role of free radicals in peptic ulcer and gastritis.
AB  - BACKGROUND/AIMS: It has been suggested that the free radicals are closely related
      with peptic ulcer disease and gastritis. Although many studies have been
      undertaken to clarify the role of oxygen-derived free radicals, most of them were
      carried out in animal models. The aim of this study was to assess the reactive
      oxygen species activity and the damage in Helicobacter pylori-infected gastric
      mucosa in humans. METHODS: In a total group of 42, there were fifteen cases of
      peptic ulcer, 14 cases of gastritis and 12 control subjects. Measurement of
      gastric mucosal malondialdehyde concentrations, which is the end - product of
      lipid peroxidation, was used to assess oxidative damage to membranes in patients
      with peptic ulcer and gastritis. Mucosal reduced glutathione glutathione
      concentrations were also measured in order to study whether reactive oxygen
      species generation affects levels of the antioxidant peptide. malondialdehyde and
      glutathione content was then measured in biopsies taken from the gastric antrum.
      RESULTS: Tissue levels of glutathione were significantly (p<0.001) and
      malondialdehyde was higher (p<0.001) in patients with peptic ulcer compared to
      controls. In patients with gastritis, glutathione was also lower (p<0.001) and
      malondialdehyde higher (p<0.01). CONCLUSIONS: Depletion of gastric mucosal
      glutathione in cases with H.pylori positive peptic ulcer and gastritis may be
      caused by accumulation of free radicals that can initiate membrane damage by
      lipid peroxidation.

PMID- 14593537
TI  - Predictors of vitamin B12 deficiency: age and Helicobacter pylori load of antral
      mucosa.
AB  - BACKGROUND/AIMS: The aim of this study was to assess the frequency of vitamin B12
      deficiency in patients with non atrophic gastric mucosa and any relationship
      between the presence of vitamin B12 deficiency and demographic, hematologic, and
      histopathologic parameters. METHODS: Three hundred and ten patients with no
      gastric mucosal atrophy on histologic evaluation were included in the study.
      Chronic inflammation, neutrophil activity and H. pylori load were scored using
      the Sydney classification system. Variables that might influence or predict the
      presence of vitamin B12 deficiency (age, gender, hemoglobin, mean corpuscular
      volume, serum folate level, scores of histologic parameters) were evaluated by
      univariate/multivariate analysis. RESULTS: The percentages of patients with
      vitamin B12 concentrations of < 250 pg/mL, < 200 pg/mL, and =100 pg/mL were
      67.4%, 46.8% and 6.5% respectively. Patient age and all three histologic were
      inversely related to vitamin B12 deficiency (p<0.05). By multivariate analysis,
      factors independently associated with serum vitamin B12 deficiency were age and
      antral H. pylori load (p<0.05). CONCLUSIONS: The higher frequency of vitamin B12
      deficiency in this study compared with a western study may be a reflection of the
      effect of H. pylori infection on serum vitamin B12 level. In addition, age was
      shown to be an independent risk factor for vitamin B12 deficiency irrespective of
      gastric atrophy. It is already known that the presence of H. pylori on gastric
      mucosa influence serum vitamin B12 levels. Hematologic parameters are not useful
      in predicting the deficiency of this vitamin.

PMID- 14593538
TI  - Dietary nitrate and nitrite levels in an endemic upper gastrointestinal
      (esophageal and gastric) cancer region of Turkey.
AB  - BACKGROUND/AIMS: The aim of this study was investigate nitrate and nitrite levels
      in some traditional foods and drinking water in Van, an endemic upper
      gastrointestinal (esophageal and gastric) cancer region of Eastern Turkey.
      METHODS: Cheese with added herbs, drinking water, bread baked by wood fire and
      bread baked by burning animal manure specimens collected in the Van region were
      analyzed by Stahr's modification method. Nitrite was reduced to nitrate by the
      following three reagents: hydrazine sulphate ((NH2) 2SO4), CuSO4 and NaOH.
      Nitrate was then determined by coupling reagent containing sulphanlyamide,
      phosphoric acid and N-1-naphtyl ethylendiamine dihydrochloride. RESULTS: Nitrate
      and nitrite levels of all traditional foods and nitrite levels of drinking water
      were very significantly elevated compared to standard values (p<0.001- 0.01).
      CONCLUSIONS: These findings suggest that the influence of a traditional diet rich
      in nitrate and nitrite is significant in the development of endemic upper
      gastrointestinal (esophageal and gastric) cancers in the Van region of Turkey.

PMID- 14593539
TI  - Mast cell density and neuronal hypertrophy in patients with acute appendicitis.
AB  - BACKGROUND/AIMS: In the gastrointestinal system, the relationship between the
      enteric nervous system and mast cells has been described in normal and
      pathological conditions. However, a few studies have evaluated the association
      between the numbers of mast cells and the enteric nervous system in acute
      appendicitis. The aim of this study was to immunohistochemically investigate the
      relationship between mast cell density and the enteric nervous system in cases
      with clinically and histopathologically diagnosed acute appendicitis and in
      normal appendices. METHODS: Twenty-five patients with acute appendicitis and 12
      cases with normal appendices were included in our study. Mast cell tryptase and
      PGP 9.5 immunostained tissue sections were subjected to quantitative image
      analysis. RESULTS: Our results showed that mast cell density, number of Schwann
      cells and the number and size of ganglia were significantly greater in acute
      appendicitis than in the control group (p<0.05). A strong correlation between
      mast cell density and neuronal proliferation and hypertrophy was detected only in
      cases with acute appendicitis. We failed to detect any relationship between mast
      cell density and neural components in the control group. CONCLUSIONS: Our
      findings indicate that mast cells could be one of the important cell populations
      responsible for nerve proliferation and hypertrophy in clinically and
      histopathologically diagnosed acute appendicitis.

PMID- 14593540
TI  - Colonoscopy without sedation.
AB  - BACKGROUND/AIMS: In Turkey, colonoscopy is a procedure generally performed with
      intravenous sedation and analgesia. Most of the complications of colonoscopy are
      related to sedation. The aims of this study were to determine the percentage of
      patients who could successfully undergo nonsedated colonoscopy without sedation
      and to assess patient tolerance and acceptance. METHODS: The study included 120
      consecutive patients undergoing colonoscopy by two endoscopists in our endoscopy
      unit. The procedure routinely began without sedation, which was later given
      (midazolam and hyoscine butylbromide) only if significant discomfort occurred.
      Parameters of blood pressure, oxygen saturation and heart rate were measured
      before and during colonoscopy. After the procedure patients were asked to rate
      their pain on a four point scale 1=no pain, 2=slight, 3=moderate, 4=severe and
      they were also asked if they would be willing to undergo colonoscopy again
      without sedation. RESULTS: Eighty eight percent of all colonoscopies were
      completed without sedation. Mean PaO2 was 96.46 in nonsedated patients and 93.90
      (significant p<0.05) in sedated patients. No difference was found between blood
      pressure and pulse rate of nonsedated and sedated patients. The mean pain score
      was 2.0 for the nonsedated patients and 3.8 (significant p<0.05) for the sedated
      patients. Eighty eight percent of patients stated that they would be willing to
      undergo colonoscopy without sedation again. CONCLUSIONS: In experienced hands,
      colonoscopy without sedation can be completed successfully in most patients,
      without any complications and use of extra instrumentation.

PMID- 14593541
TI  - Nodular regenerative hyperplasia of the liver: a case report.
AB  - Nodular regenerative hyperplasia of the liver is characterized by hepatocellular
      nodules distributed throughout the liver in the absence of fibrous septa between
      the nodules. In the literature, most reports have been single cases so that the
      prevalence and clinical significance of the disease is not exactly known. The
      critical lesion is obliterative portal venopathy which is obstruction to terminal
      radicals of hepatic arterioles and portal venules, possibly secondary to
      endothelial cell damage. Resultant hepatic ischemia may be responsible for
      induction of the nodular regenerative change. Portal hypertension which is
      secondary to nodular regenerative hyperplasia and is often complicated by
      bleeding esophageal varices. We report a rare case of nodular regarative
      hyperplasia of the liver, with onset of symptom in childhood.

PMID- 14593542
TI  - Polyarteritis nodosa presenting with necrotising appendicitis and hepatic
      aneurysm rupture.
AB  - Polyarteritis nodosa is a necrotizing vasculitis which affects small and medium
      sized arteries. The clinical features of the disease vary according to the site
      and extent of involvement. Aneurysmal dilatation and thrombosis in the arteries
      of the liver and gastrointestinal tract have been reported in polyarteritis
      nodosa. However, rupture of the hepatic aneurysm and necrotizing appendicitis due
      to polyarteritis nodosa are uncommon; indeed a case in which these have occurred
      together has not been reported to date. In this case report, a patient with
      necrotizing appendicitis and hepatic aneurysm rupture due to underlying
      poliarteritis nodasa is presented. Extensive intraabdominal hematoma and
      appendicitis were treated surgically and complete recovery was achieved.

PMID- 14593544
TI  - Endoscopic extraction of living fasciola hepatica: case report and literature
      review.
AB  - Fasciola hepatica infestation is known to cause bile duct inflammation and
      biliary obstruction. Endoscopic retrograde cholangiopancreatography shows
      distinct features in some patients with fascioliasis, but the condition may be
      overlooked in chronic cases. The endoscopic retrograde cholangiopancreatograpy
      images must be carefully examined to rule out other possible causes of
      irregularity and thickening of the common bile duct wall. Parasite removal during
      endoscopic retrograde cholangiopancreatograpy is one therapeutic option in
      patients with acute obstructive cholangitis due to F. hepatica. We present a case
      of fascioliasis-induced acute cholangitis that was diagnosed and treated via
      endoscopy. A review of the literature on extraction of living parasites is also
      included.

PMID- 14593545
TI  - A Peutz-Jeghers syndrome case with iron deficiency anemia and jejuno-jejunal
      invagination.
AB  - Peutz-Jeghers syndrome is an autosomal dominantly inherited rare syndrome
      characterized by mucocutaneous pigmentations, with intestinal and extraintestinal
      polyps. It is accepted to be a precancerous syndrome. The polyps can cause anemia
      and intestinal obstruction and intussuception. We present a young patient
      admitted to our clinic with a history of recent gastrointestinal bleeding. Upper
      and lower gastrointestinal endoscopic examinations revealed multiple polyps
      located in the stomach, jejunum, rectum and terminal ileum. In addition, there
      were many mucocutaneous pigmentations on the lips, buccal mucosa and finger and
      toe nails. Jejunal polyps were found to be the cause of jejuno-jejunal
      invagination and iron deficiency anemia. Histopathological evaluation of the
      polyps revealed hamartomatous polyps of Peutz-Jeghers syndrome and this diagnosis
      was supported by a dermatology specialist. It is suggested that any patient
      presenting with ileus attacks and findings of anemia should be investigated for
      polyps and mucocutaneous pigmentations of the precancerous Peutz-Jeghers
      syndrome.

PMID- 14593543
TI  - Is hyperbilirubinemia a component or just a coincidence of familial mediterranean
      fever: a case report and review of the literature.
AB  - Familial Mediterranean fever is a multisystem disorder, usually seen in subjects
      of Mediterranean and Middle Eastern origin, characterized by recurrent bouts of
      fever and pain due to inflammation of the peritoneum, synovia, or pleura. In this
      article we report a case of Familial Mediterranean fever with recurrent abdominal
      pain and hyperbilirubinemia, review the literature and discuss whether the
      hyperbilirubinemia is co-existant or a feature of the disease.

PMID- 14593546
TI  - Hepatic abscess in brucellosis: a case report.

PMID- 14593549
TI  - Diagnostic criteria in polycystic ovary syndrome.
AB  - Part of the difficulty in understanding polycystic ovary syndrome (PCOS) and
      interpreting the dense literature surrounding it is that there is no universally
      accepted clinical definition. The varying definitions influence the incidence,
      prevalence of sequelae, and response to treatment. PCOS is clearly heterogeneous
      and its etiology is still speculative. Over the years it has evolved from a
      "disease" to a "syndrome," the latter which includes a variety of potential signs
      and symptoms, including oligo-ovulation, biochemical or clinical
      hyperandrogenism, polycystic ovaries, and insulin resistance. There is no single
      diagnostic criterion that can be recommended for diagnosis of PCOS. While
      hyperandrogenemia, specifically elevated bioavailable testosterone, is
      intellectually appealing, the evidence in terms of long-term sequelae identified
      by such a test is still weak. The recognition of oligo-ovulation primarily relies
      on patient history. Currently both consensus and the preliminary evidence-based
      trials support a combination of hyperandrogenemia and oligo-ovulation, in the
      absence of known causes, as diagnostic criteria, but there are also strong
      proponents of using ovarian morphology to identify and diagnose the syndrome.
      There are no simple clinically validated biochemical tests of insulin resistance.
      Further identification of specific causes, and elimination of the multiple
      phenocopies that make up PCOS, will ease its diagnosis.

PMID- 14593550
TI  - Pharmacologic treatment of polycystic ovary syndrome.
AB  - Women with polycystic ovary syndrome (PCOS) most often seek treatment for
      reduction of hair growth and/or acne, restoration of menstrual cyclicity, and
      infertility. In addition, these patients are increasingly seeking advise and
      treatment for the metabolic abnormalities related to PCOS (e.g., insulin
      resistance and type 2 diabetes). In this review, we outline the pathophysiologic
      events underlying the cutaneous manifestations of androgen excess and provide a
      rationale for use of the various pharmacologic agents available for treatment.
      Options for the treatment of the reproductive abnormalities (menstrual
      dysfunction and interfility) are presented. Finally, the metabolic manifestations
      of PCOS are reviewed and their treatment is discussed.

PMID- 14593551
TI  - The diagnosis and management of hirsutism.
AB  - Approximately 10% of women of childbearing age are hirsute, which is defined as
      the presence of coarse terminal hairs in androgen-dependent areas on the face and
      body. It not only is a source of psychological discomfort but also may be a sign
      of an underlying medical condition. This article reviews the pathophysiology,
      diagnosis, evaluation, and treatment of hirsutism.

PMID- 14593553
TI  - Polycystic ovary syndrome in adolescence.
AB  - Polycystic ovary syndrome (PCOS) is a relatively common disorder among adolescent
      women. The typical clinical features including menstrual irregularities and
      hirsutism are usually not apparent until middle to late adolescence. Yet studies
      suggest that PCOS may begin in early puberty. Young women with premature
      pubarche, a family history of PCOS, Caribbean Hispanic and African American
      ancestry, and/or obesity are more likely to develop PCOS. Adolescents with PCOS
      may have elevated total or free testosterone, androstenedione, and luteinizing
      hormone levels; insulin resistance; and hyperinsulinemia. The laboratory
      evaluation and management of the adolescent with suspected PCOS should be
      individualized on the basis of the clinical features and symptoms. The
      cornerstone of most treatment strategies includes either a combination oral
      contraceptive or progestin to decrease testosterone levels and regulate the
      menstrual cycle. Consideration of insulin-sensitizing agents, antiandrogens,
      topical treatments for acne and excess facial hair, and hair removal is dependent
      on the patient's symptoms and concerns. A healthy approach to eating, in some
      cases weight loss, and exercise is encouraged to reduce the risk of
      cardiovascular disease and type 2 diabetes mellitus. Management of the adolescent
      with PCOS is challenging and often requires a supportive, multidisciplinary team
      approach for optimal results.

PMID- 14593552
TI  - 21-hydroxylase-deficient nonclassic adrenal hyperplasia: the great pretender.
AB  - Polycystic ovary syndrome (PCOS) affects about 4 to 6% of women of reproductive
      age and accounts for at least 75% of hyperandrogenic patients. PCOS is diagnosed
      by the presence of oligo-ovulation and hyperandrogenism after the exclusion of
      related disorders, such as 21-hydroxylase-deficient nonclassic adrenal
      hyperplasia (NCAH). In turn, NCAH is a homozygous recessive disorder, diagnosed
      by a corticotropin-stimulated 17-hydroxyprogesterone (17-HP) level greater than10
      ng/mL (30.3 nmol/L) and confirmed by genotyping of the CYP21 gene. The prevalence
      of NCAH is approximately 50 times less than that of PCOS, affecting between 1 and
      10% of hyperandrogenic women, depending on ethnicity. However, it is generally
      difficult to distinguish NCAH from PCOS solely on clinical grounds, as both
      demonstrate varying degrees of hyperandrogenism and ovulatory dysfunction. Most
      PCOS patients have insulin resistance, in contrast to those with NCAH. Likewise,
      polycystic ovaries are observed in up to 40% of NCAH patients. Both disorders
      have a strong familial component. The only method that allows the separation of
      NCAH from PCOS patients is the measurement of 17-HP levels. In conclusion, PCOS
      and NCAH have differences in prevalence and pathophysiology. However, because the
      disorders have significant clinical and hormonal similarities, the measurement of
      17-HP, preferably basally as a screening method, should be incorporated into the
      evaluation of all hyperandrogenic patients.

PMID- 14593555
TI  - In vitro fertilization in the PCOS patient: clinical considerations.
AB  - Of all the patients undergoing in vitro fertilization, the patient with
      polycystic ovary syndrome (PCOS) is probably the most challenging. This is due to
      the fact that the majority of patients exhibit exaggerated responses to exogenous
      gonadotropins, frequently leading to an increased rate of cancellation of a
      treatment cycle. Even those who proceed to oocyte retrieval, and in spite of an
      increased number of oocytes retrieved, poor fertilization rates may be
      encountered, probably secondary to an increased rate of oocyte immaturity. To
      compound the problem further, even fertilized eggs in these patients, generally
      speaking, may show lower cleavage rates, and this leads to decreased implantation
      and pregnancy rates. In addition, these are patients who exhibit a much higher
      incidence of ovarian hyperstimulation syndrome, which puts the patient's health
      at great risk. Possibly, some of these problems may be inherent in the PCOS
      ovary. Nevertheless, it is possible that modifications of clinical protocols may
      improve outcome.

PMID- 14593558
TI  - Advanced imaging of gout.
AB  - Gout is a metabolic disorder in which there is either an increase in production
      or a decrease in excretion of uric acid leading to hyperuricemia. Long-lasting
      hyperuricemia causes the deposition of monosodium urate crystals in the joints
      and soft tissues triggering gouty arthritis and, if not properly treated, the
      formation of gouty tophi. Characteristic of gout are well-defined, punched-out
      erosion with overhanging edges, with preservation of the joint space, lack of
      periarticular osteopenia, asymmetrical involvement, soft tissue nodules, and
      intraosseous calcifications. On magnetic resonance imaging, tophi usually have
      low signal intensity on both TI- and T2-weighted images and a variable
      enhancement pattern.

PMID- 14593554
TI  - Cardiovascular health in women with polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) is arguably the most common endocrinopathy among
      women of reproductive age. Women with PCOS have clinical characteristics that are
      associated with insulin resistance, vascular dysfunction, hypertension, and
      dyslipidemia. Although definitive data for increased cardiovascular events in
      women with PCOS are lacking, case-control studies have documented an increased
      risk of preclinical cardiovascular disease. Thus, PCOS should be viewed as a
      chronic condition that may ultimately have long-term health impacts and patients
      should be counseled to reduce cardiovascular risk factors through weight control,
      exercise, and/or pharmacologic treatments.

PMID- 14593559
TI  - Calcium pyrophosphate dihydrate crystal deposition disease.
AB  - Calcium pyrophosphate dihydrate (CPPD) crystal deposition disease is
      characterized by the accumulation of pyrophosphate dihydrate crystals in
      articular and periarticular tissues. Various terms have been utilized to describe
      this arthropathy, which has led to some confusion. CPPD crystal deposition
      disease is among many conditions that may result in crystal deposition within
      cartilage. Chondrocalcinosis is a pathologic and radiographic term denoting
      calcification of cartilage within joints including both hyaline articular
      cartilage and fibrocartilage. Pseudogout is a clinical term applied to an acute
      inflammatory process in a joint(s) mimicking a gout attack. Pseudogout is just
      one of the multiple clinical presentations for CPPD crystal deposition disease.
      Pyrophosphate arthropathy is a term that has been used to describe the peculiar
      pattern of joint destruction associated with CPPD crystal deposition disease.
      This article reviews the protean manifestations of CPPD crystal deposition
      disease with emphasis on diagnostic imaging.

PMID- 14593560
TI  - Hydroxyapatite crystal deposition disease.
AB  - Hydroxyapatite (HA) crystal deposition disease (HADD) is a well-recognized
      systemic disease of unknown etiology that is caused by para-articular and/or
      intra-articular deposition of HA crystals. The disease is clinically manifested
      by localized pain, swelling, and tenderness about the affected joint along with
      variable limitation of joint motion, although not all patients are symptomatic.
      Plain radiographs may show calcifications of varying size and shape in the para
      articular tendons, bursae, and capsule. The disease may be mono- or polyarticular
      in distribution. The shoulder is most commonly involved with calcification in the
      supraspinatus tendon. When intra-articular, HA crystals can cause joint
      destruction. Any joint can be involved; the shoulder is most commonly affected,
      resulting in "Milwaukee shoulder." Treatment of HADD usually requires use of
      analgesics, local heat, needling with or without aspiration of the calcific
      deposits, steroid injections, and, at times, even surgery for relief of pain.

PMID- 14593561
TI  - Imaging of amyloid arthropathy.
AB  - Amyloidosis is a disease complex caused by the extracellular deposition of an
      insoluble protein called amyloid. Amyloid arthropathy results from localized
      amyloid deposition in and around the joints. This article discusses the types of
      amyloidosis associated with amyloid arthropathy and presents their characteristic
      imaging findings.

PMID- 14593562
TI  - Imaging of pigmented villonodular synovitis.
AB  - Pigmented villonodular synovitis (PVNS) is a rare, benign, idiopathic
      proliferative disorder of the synovium that results in villous and/or nodular
      formation in joints, tendon sheaths, and bursae. The disease can be localized or
      diffuse. Patients with this condition typically present with symptoms of mild
      discomfort and associated stiffness of the involved joint; however, the spectrum
      of presentations is broad. Diagnosis of PVNS can be clinically difficult, and
      plain radiographs are usually nonspecific. Magnetic resonance (MR) imaging is a
      highly diagnostic modality in characterizing PVNS when it contains hemosiderin
      deposits exhibiting low signal intensity on all MR image pulse sequences. This
      article discusses the presentation, pathology, differential diagnosis, diagnostic
      modalities as well as various treatment options of PVNS.

PMID- 14593563
TI  - Imaging of neuropathic arthropathy.
AB  - Neuropathic arthropathy is a chronic, progressive joint degeneration with bone
      fragmentation, ligamentous instability, and dislocation. Diabetes is the leading
      cause of neuropathic arthropathy. Conventional radiography is the most commonly
      used imaging modality for diagnosing neuropathic arthropathy. The disease is
      mostly the hypertrophic type and is manifested by sclerosis of the bone,
      fragmentation, joint destruction, swelling, large joint effusion, and large
      osteophyte formation. Computed tomography, magnetic resonance imaging and
      radionucleide scintigraphy are helpful for diagnosing the disease and may help in
      distinguishing neuropathic arthropathy from septic arthritis and osteomyelitis.

PMID- 14593564
TI  - Arthritis associated with dermatologic conditions.
AB  - This article should alert radiologists to be on the lookout for clues in the
      clinical history for signs of joint disease or other multisystem involvement in
      patients with a skin disease. A skin rash may be the first indication of a
      serious disease that prompts a patient to seek medical attention. In this review,
      examples of joint-skin associations are shown, and a table is presented that
      includes a comprehensive list of these conditions. The classification system is
      partly anatomic and partly etiologic, including diseases of the epidermis,
      dermis, sebaceous glands and sweat glands, tumors, immunologic and collagen
      vascular diseases, infections, and environmental diseases.

PMID- 14593565
TI  - [Ceramic model for temporal bone exercises--an alternative for human temporal
      bones?].
AB  - BACKGROUND: The complexity of the temporal bone anatomy makes it necessary to
      train in a model before starting middle ear surgery. The classical object are
      human cadaver temporal bones, but these are not always available for different
      reasons. Alternatively in cooperation between the department of otolaryngology,
      head and neck surgery of the University of Jena and the 3di company Jena,
      Germany, a calcium sulfate based model was developed. METHODS: During a temporal
      bone course at the Bugando Medical Centre, Mwanza, Tanzania, these ceramic
      temporal bone specimens were used for training. Because of the lack of drills,
      the specimens were worked on in chisel and carving technique. All participants
      were beginners in ear surgery. Classical procedures in mastoid surgery were
      performed: Exposing of sigmoid sinus, facial nerve, labyrinth, dura, jugular bulb
      and internal carotid artery. RESULTS: The temporal bone models were very useful
      for these exercises. Good exposure was possible for the dura, the facial nerve
      and the major blood vessels. The possibility of exposing tinier structures like
      the labyrinth was still insufficient. Nevertheless the understanding of the 3
      dimensional anatomy of the temporal bone using the ceramic model was excellent.
      The relationship of all important anatomical structures could be taught
      intensively. CONCLUSIONS: Particularly for beginners or in cases where human
      temporal bones are not available the calcium sulfate based temporal bone is an
      alternative training model for mastoid and middle ear surgery.

PMID- 14593567
TI  - [In vitro culture of cells from respiratory mucosa on foils of collagen, poly-L
      lactide (PLLA) and poly-3-hydroxy-butyrate (PHB)].
AB  - BACKGROUND: The replacement of respiratory mucosa after surgical resections at
      different locations in the ENT-field (trachea, nasal septum, sinus maxillaris)
      seems to be essential or at least of great benefit for patients. Presently a
      satisfying solution for this challenge does not exist. Therefore we have analysed
      the growth of cells from respiratory mucosa on different matrices. METHODS: Cell
      cultures are initiated mainly by growing out cells from tissue pieces but also by
      seeding of cells after enzymatic dissociation (sequential trypsinization) of
      mucosa. Cells were cultured with serum-containing and serum-free media on 3
      different foils: made of collagen, of Poly-L-lactic acid (PLLA) and Poly
      hydroxybutyric acid (PHB). Culturing time was on average about 4 - 5 weeks.
      RESULTS: On all tested materials fibroblasts and epithelial cells have grown in
      principle. PLLA was the material with best properties concerning the aim of this
      study whereas culturing of cells on PHB only happens after surface modification
      by amino-functionalisation with plasma treatment. Visualisation of cells on
      materials of collagen could not realised by light-microscopy due to the 3
      dimensional structure and the optical properties of this material. Here the
      cultures were analysed by cell membrane staining and by REM. We could not find a
      differentiation of epithelial cells with beating cilia 6 weeks after starting the
      culture. However 20 days after starting the culture on PLLA (good conditions for
      observation with light-microscope) cells with beating cilia could be observed, in
      our opinion resulting from dissociated cells from tissue pieces and not from
      proliferated cells. CONCLUSIONS: In principle the analysed materials are useful
      for the culturing of cells from respiratory mucosa. However, for obtaining
      differentiated epithelial cells the culture conditions have to be modified.

PMID- 14593566
TI  - [Near infrared stimulation of the equilibrium organ--first clinical experiences].
AB  - BACKGROUND: A new method for the stimulation of the organ of equilibrium by means
      of a broad-scale and monochromatic near infrared emission was developed. This
      method should be examined within the framework of a pilot study, evaluated and
      its clinical possible applications examined. PATIENTS AND METHODS: Healthy
      probands (n = 15), patients with a radical cave of the ear (n = 5), patients with
      a defect of the tympanic membrane (n = 5) and spontaneous nystagmus (n = 5) were
      examined. In healthy probands an irritation with broad-scale as well as
      monochromatic near infrared (NIR) was performed and compared with a water
      irrigation (44 degrees, 50 ml in 30 seconds). The subjective, local feelings
      during the application and the appearance of giddiness according to irritation
      were recorded and the nystagmus was registered by means of videonystagmography.
      In patients with radical cave of the ear and tympanic membrane defects, a broad
      scale NIR-irritation before a comparative irritation with warm air (44 degrees)
      was performed exclusively. RESULTS: In all healthy probands, a nystagmus reaction
      could be seen with broad-scale and monochromatic NIR. Compared to the hot water
      irritation slow phase velocity (SPV) was decreased however registrable by means
      of Frenzel glasses and electronystagmography during the culmination stage. In
      patients with radical cave (n = 4) and tympanic membrane defects (n = 3) showing
      paradoxical nystagmus reaction during hot air irritation, a nystagmus to the site
      of stimulation resulted by means of light calorisation. In patients with a
      spontaneous nystagmus an attenuation (n = 1) or inversion (n = 2) could be
      achieved by NIR-radiation. CONCLUSIONS: The method of the NIR-radiation is
      suitable in clinical practice for the caloric test proofing warm reaction.
      Vaporization cold does not occur. The application of heat charm is better
      proportionable and steerable than during air irritation. The procedure is
      sterile, noiseless and non-contact. Difficulties in interpretation of results of
      vestibular tests because of evaporation coldness do not occur.

PMID- 14593568
TI  - [Intralesional cidofovir injections for recurrent laryngeal papillomatosis: first
      results].
AB  - BACKGROUND: The treatment of recurrent laryngeal papillomatosis still presents an
      important therapeutic problem. This primarily benign disease of the larynx is
      caused by an infection with the human papilloma virus (HPV) and forms epithelial
      neoplastic papillomas. Therapy in larynx obstructing papillomatosis usually
      requires laser ablation. Cidofovir acts virustatically as an nucleosidanalogon.
      Currently pilot studies investigate the effectiveness of intralesional Cidofovir
      injection. PATIENTS AND METHODS: The present study covers the period from October
      2001 to March 2003. Seven patients, age of five to 70 years, were treated with
      intralesional injections of Cidofovir after microlaryngoscopic ablation of
      laryngeal papillomas. In all patients papillomatosis was confirmed histologically
      and a clinical-phoniatric examination and a photo documentation pre- and
      postoperatively was carried out. We treated patients to a maximum of six
      sessions. RESULTS AND CONCLUSIONS: After three to six sessions of laser ablation
      of the papillomas and intralesional injections with Cidofovir a distinct
      papilloma reduction could be observed in all patients and in two cases a complete
      remission was achieved. The follow-up period of seven to 15 months revealed no
      recurrent laryngeal papillomatosis. The majority of patients showed a defined
      voice improvement. There were no local or systemic side-effects caused by the
      virustatic drug. Intralesional injection of Cidofovir appears to develop into a
      promising adjuvant therapy option in recurrent laryngeal papillomatosis. First
      results of the study seem to achieve a considerable reduction of the previously
      high rate of recurrence of laryngeal papillomatosis.

PMID- 14593569
TI  - [Capsular rupture of lymph node metastases as most significant prognostic factor
      in head and neck squamous cell carcinomas--Hamburg experiences].
AB  - BACKGROUND: TNM classification of squamous cell carcinomas of the head and neck
      contains only size and number of the lymph node metastases. The histological
      criterion of capsular rupture and its prognostic significance was assessed by an
      exact histological scheme of capsular rupture and extracapsular spread of the
      metastasis and was compared with N0 or lymph node metastases without capsular
      rupture respectively. METHODS: Incidences of distant metastases, tumor
      recurrences, and survival of 194 consecutive patients with squamous cell
      carcinomas of the head and neck were investigated. Lymph node metastases were
      examined by the gradual histological scheme and patients were rated according
      their histological diagnosis. RESULTS: The classification N0/intranodal tumor
      growth/extranodal tumor growth resulted in a 5-year survival rate of 74%/62%/25%.
      According to the classification 67%/72%/37% of the patients were without local
      recurrent tumor and without distant metastases were 81%/79%/48% after 5 years.
      CONCLUSIONS: Capsular rupture seems to contain more decisive prognostic value as
      the criterion of only lymphatic metastatic disease. The histological scheme
      allows an exact assessment of the capsular rupture or the metastatic pattern of
      the lymph node. Because of its prognostic significance and individual therapeutic
      consequences the easily reproducible criterion of capsular rupture is a useful
      completion to current TNM classification.

PMID- 14593570
TI  - [Experimental and clinical investigations on the inhibition of secretion of the
      major salivary glands with botulinum toxin A].

PMID- 14593571
TI  - [An update on cystic fibrosis for the ENT-specialist].
AB  - Patients with cystic fibrosis (CF) show a high morbidity with
      otorhinolaryngological disorders, especially of the nasal airways and the
      paranasal sinuses. Because of the underlying basic genetic defect of the
      respiratory mucosa in CF many patients suffer from chronic rhinosinusitis,
      partially combined with the development of nasal polyps. Chronic rhinosinusitis
      in CF is different from chronic sinusitis in Non-CF-patients. In CF mainly
      neutrophils are found in the nasal epithelium, whereas in Non-CF-patients
      eosinophils predominate. In CF-sinuses a characteristic mucosal thickening and
      increase of high viscous mucus is seen which is not typically found in Non-CF
      patients with chronic sinusitis. The respiratory mucosa in CF is mostly colonized
      with Staphylococcus und Pseudomonas. These bacteria participate in the damage of
      the respiratory epithelia and infection of the paranasal sinuses. Repeated
      administration of antibiotics frequently fails to reduce subjective symptoms of
      the patients or polyp formations, and sinus surgery is often necessary. New
      therapeutic approaches, such as postoperative inhalation with Dornase-alpha, are
      only empiric and not frequently recommended yet. Besides the strict indication
      for sinus surgery, which should only be performed on an inpatient basis, the
      hygienic handling with CF-patients needs special attention, particularly in
      medical centers with many patients. An effective genetic therapy for CF is
      currently not available.

PMID- 14593573
TI  - [Chologenic abscess after radiofrequency ablation of a cholangiocellular
      carcinoma].
AB  - HISTORY: Persistent fever occurred after palliative radiofrequency thermal
      ablation (RFTA) of a solitary liver metastasis in a 62-year-old patient with
      cholangiocarcinoma treated by cholecystectomy, lymph-adenectomy, resection of the
      ductus hepatocholedochus and biliodigestive anastomosis. INVESTIGATIONS AND
      DIAGNOSIS: Tests for inflammatory disease were elevated. Sonography revealed an
      echo-free lesion in the region of the previous RFTA. Percutaneous drainage
      produced purulent material. TREATMENT AND COURSE: The liver abscess communicating
      with the bile duct system was drained and treated with antibiotics. CONCLUSION: A
      liver abscess is a rare complication of RFTA. A preexisting biliodigestive
      anastomosis may be an independent risk factor for this rare complication.

PMID- 14593572
TI  - [Ambulant care of patients in the terminal phase of malignant tumor: answers by
      general practioners in Thuringia to a questionnaire].
AB  - BACKGROUND AND OBJECTIVE: Palliative care and care of the dying are not widely
      taught in medical education. Yet, through the guidelines of the Federal Medical
      Council (Bundesarztekammer), doctors are obliged professionally to accompany the
      dying process. Systematic studies concerning doctors' motivation and action in
      this special situation are rare. This study aims to evaluate the views and
      attitudes of general practitioners towards the care for cancer patients in the
      terminal stage of disease. METHODS: In association with the project of the German
      Ministry of Health "Patienten als Partner-Tumorpatienten und ihr Mitwirken in
      medizinischen Entscheidungen" ("Patients as partners: patients with malignant
      tumor and their collaboration in medical decision making"), a questionnaire was
      designed for general practitioners based on qualitative interviews. The self
      guiding questionnaire comprised questions concerning death and dying, patient
      doctor relationship and day-to-day medical actions. RESULTS: 505 general
      practitioners (GPs) received the questionnaires. 170 were filled in and sent back
      (33%). The GPs felt responsible for the care of the dying patients. Pain control
      was the main goal (97%). Symptom control was thought to be important/very
      important in 87%, the application of life-prolonging measures in 12 %. Basic
      analgesic medication was prescribed by 93% of GPs. 89%/77% of the general
      practitioners answered that they were satisfied with the technical equipment of
      the hospital/clinic, whereas there was a dissatisfaction with psychological and
      spiritual support. CONCLUSION: General practitioners widely accept their
      responsibility for the care of the dying patients. Pain control is the major goal
      in this group of patients. Some items (use of co-analgesia, prescription of peak
      analgesia) seem to be open to improvements. Despite a high motivation, general
      practitioners show their dissatisfaction with some aspects of the care for dying
      people. Palliative care teams could be helpful in this situation.

PMID- 14593574
TI  - [Macrophagic myofasciitis: inflammatory, vaccination-associated muscular
      disease].
AB  - HISTORY AND ADMISSION FINDINGS: A 67-year-old man presented with a 6-week history
      of slowly progressive muscle pain and generalized muscular weakness. Neurological
      examination showed symmetrical proximal weakness (MRC grade 4/5). INVESTIGATIONS:
      Laboratory tests revealed an elevated CK level of 124 U/l (normal < 80). Needle
      EMG showed pathological spontaneous activity in proximal muscle groups. A
      diagnostic muscle biopsy taken from the left deltoid muscle revealed a
      characteristic infiltrate of PAS-positive and acid phosphatase-positive
      macrophages. Electron microscopic analysis of muscle tissue failed to demonstrate
      aluminium hydroxide inclusion. Serological analysis excluded antibodies against
      HAV and HBV but was compatible with a previous tetanus vaccination (antibody
      titre of 2.3 IE/ml). TREATMENT: A 2-year treatment with steroids and azathioprine
      led to complete recovery of muscle strength without relapse after discontinuing
      the immunosuppression. CONCLUSION: Macrophagic myofasciitis (MMF) is a rare
      inflammatory muscle disorder characterized by a characteristic infiltration of
      muscle tissue by PAS-positive macrophages, which is caused by pathological
      persistence of vaccine-derived aluminium hydroxide. The diagnosis can only be
      established by an open muscle biopsy from the muscle that was used for
      intramuscular vaccination.

PMID- 14593576
TI  - [Visceral adipose tissue and metabolic syndrome].

PMID- 14593575
TI  - [Dosage equivalents of AT1-receptor antagonists available in Germany].

PMID- 14593577
TI  - [Pathophysiologic basis for prevention and pharmacotherapy of benign cold thyroid
      nodules].

PMID- 14593578
TI  - [The benefit of a population based mammography screening--scientifically proven
      or not?].

PMID- 14593579
TI  - [Notification of the medical expert opinion to the insured in private health
      insurance. Decision of the Federal Court, 6/11/2003-IV ZR 418/02].

PMID- 14593580
TI  - [Are there guidelines for performance of coloscopy during drug anticoagulation?].

PMID- 14593581
TI  - [Can an intracranial aneurysm burst through an outside influence?].

PMID- 14593585
TI  - Staphylococcal peptidoglycan suppresses production of interleukin-2 by T cells
      through a T cell-derived factor induced by direct contact between T cells and
      monocytes.
AB  - During the last 2 decades, the incidence of sepsis due to gram-positive bacteria
      has increased dramatically. Nevertheless, effects of the cell-wall components
      that do not contain endotoxin, on immunity, are still largely unknown. Here, we
      demonstrate, for the first time, that the gram-positive bacterial cell-wall
      component peptidoglycan (PGN) severely inhibits the production of interleukin
      (IL)-2 by cultured human peripheral blood mononuclear cells stimulated with anti
      CD3 and anti-CD28 antibodies. Furthermore, we provide evidence that the
      inhibitory effect is mediated predominantly by a soluble mediator produced by T
      cells and that the production of the inhibitory mediator is induced by direct
      cell-to-cell contact of T cells with PGN-stimulated monocytes. The T cell-derived
      inhibitory mediator is distinct from known immunosuppressive lymphokines, such as
      IL-10 and IL-4. In light of the key role of IL-2 in cell-mediated immunity, it
      can be suggested that PGN induces the dysfunction of cell-mediated immunity.

PMID- 14593583
TI  - Helicobacter pylori reinfection is common in Peruvian adults after antibiotic
      eradication therapy.
AB  - To characterize posttreatment recurrence of Helicobacter pylori in Peru, 192
      adults with H. pylori-positive gastric biopsy specimens were monitored by (14)C
      Urea breath test, after eradication of H. pylori by use of amoxicillin,
      clarithromycin, and omeprazole. The cumulative risk of recurrence at 18 months
      was 30.3% (95% confidence interval, 21.4%-39.3%). Randomly amplified polymorphic
      DNA patterns and DNA sequence data established that, among 28 pairs of H. pylori
      isolates from pretreatment and recurrent infections, 6 (21%) were genetically
      similar, suggesting recrudescence of the previous infection, and 22 (79%) were
      different, suggesting reinfection with a new strain that differed from that
      involved in the initial infection. Eating mainly outside of the home was a risk
      factor for infection with a new strain (adjusted relative risk [RR], 5.07),
      whereas older age was a protective factor (adjusted RR, 0.20). Although an
      increase in the anti-H. pylori IgG antibody titer corresponded to recurrence,
      pretreatment and recurrent infections were similar with respect to quantitative
      culture colony counts and histologic characteristics, suggesting that neither
      prior eradication nor the memory immune response measurably alters the risk or
      burden of recurrent infection. Although eradication with antibiotics was
      successful, the high rate of reinfection suggests that treatment is unlikely to
      have a lasting public health effect in this setting.

PMID- 14593584
TI  - Identification and characterization of a phospholipase D-superfamily gene in
      rickettsiae.
AB  - The completion of the sequencing of the genomes of both Rickettsia conorii and R.
      prowazekii provides the opportunity to identify putative virulence factors within
      these strictly intracellular pathogens. A role for a phospholipase A(2) (PLA(2))
      in rickettsial pathogenicity was hypothesized, but the corresponding gene has not
      been identified. We have identified a gene that encodes a putative phospholipase
      D (PLD) and that has been detected by Southern blotting in 11 analyzed strains of
      rickettsiae. The recombinant protein is dimeric and has PLD activity, as
      demonstrated by its capacity to release [(3)H]-choline from phosphatidyl [(3)H]
      choline. This PLD is present in whole rickettsial lysates and likely is a
      virulence factor, because incubation of rickettsiae with an anti-PLD antibody
      reduced their cytotoxic activity against Vero cells. This enzyme might account
      for the activity previously attributed to PLA(2) and might be critical for the
      intracellular life of these bacteria.

PMID- 14593586
TI  - Escherichia coli K1 invasion increases human brain microvascular endothelial cell
      monolayer permeability by disassembling vascular-endothelial cadherins at tight
      junctions.
AB  - We investigated the permeability changes that occur in the human brain
      microvascular endothelial cell (HBMEC) monolayer, an in vitro model of the blood
      brain barrier, during Escherichia coli K1 infection. An increase in permeability
      of HBMECs and a decrease in transendothelial electrical resistance were observed.
      These permeability changes occurred only when HBMECs were infected with E. coli
      expressing outer membrane protein A (OmpA) and preceded the traversal of bacteria
      across the monolayer. Activated protein kinase C (PKC)-alpha interacts with
      vascular-endothelial cadherins (VECs) at the tight junctions of HBMECs, resulting
      in the dissociation of beta-catenins from VECs and leading to the increased
      permeability of the HBMEC monolayer. Overexpression of a dominant negative form
      of PKC-alpha in HBMECs blocked the E. coli-induced increase in permeability of
      HBMECs. Anti-OmpA and anti-OmpA receptor antibodies exerted inhibition of E. coli
      induced permeability of HBMEC monolayers. This inhibition was the result of the
      absence of PKC-alpha activation in HBMECs treated with the antibodies.

PMID- 14593587
TI  - Infection of U937 monocytic cells with Chlamydia pneumoniae induces extensive
      changes in host cell gene expression.
AB  - The effect of infection with Chlamydia pneumoniae on host messenger RNA
      expression in human monocytic cells with complement DNA microarrays was studied.
      The data chronicle a cascade of transcriptional events affecting 128 genes, many
      of which have not previously been reported to be affected by C. pneumoniae
      infection. Down-regulated genes are primarily associated with RNA and DNA
      metabolism, chromosomal stability, and cell-cycle regulation. Up-regulated
      messages include those for a variety of genes with important proinflammatory
      functions. Many of the up-regulated genes-including the hyaluron receptor CD44,
      vasoconstrictor endothelin-1, smooth muscle growth factor heparin-binding EGF
      like growth factor, and fatty acid binding protein-4-had been previously
      described as linked to the development of atherosclerosis and other chronic
      inflammatory diseases. C. pneumoniae-infected monocytes can contribute to the
      development and progression of diseases for which acute or chronic inflammation
      has been shown to be important, such as atherosclerosis.

PMID- 14593588
TI  - Correlation between serum doxycycline concentrations and serologic evolution in
      patients with Coxiella burnetii endocarditis.
AB  - The recommended treatment for Q fever endocarditis is a combination of
      doxycycline and hydroxychloroquine. We found a correlation between serum
      doxycycline concentrations and decreases in levels of phase 1 Coxiella burnetii
      antibodies, in 24 patients with Q fever endocarditis. Patients who had a >2-fold
      decrease in levels of phase 1 antibodies had serum doxycycline concentrations
      higher than those of the other patients (mean+/-SD, 5.29+/-1.75 vs. 3.14+/-1.40
      microg/mL; P=.003). We recommend adjusting the posology of doxycycline to achieve
      a serum concentration of at least 5 microg/mL.

PMID- 14593589
TI  - Cell-wall alterations as an attribute of Mycobacterium tuberculosis in latent
      infection.
AB  - Ziehl-Neelsen (ZN) staining is the key technique for diagnosis of mycobacterial
      infections; however, a high percentage of patients exhibit positive signs of
      tuberculosis, as indicated by pathology, culture of mycobacteria, and polymerase
      chain-reaction analysis, and yet show negative results on ZN staining. In this
      report we present evidence that such ZN-negative specimens represent
      Mycobacterium tuberculosis bacilli in a dormant state with distinct cell-wall
      alterations: the classical cell-wall composition-dependent ZN staining of M.
      tuberculosis in lung sections gradually discontinued with persistence of
      infection, both in mice and in human patients; in contrast, detection of
      mycobacteria by cell-wall composition-independent staining using a polyclonal
      anti-M. bovis Bacille-Calmette-Guerin serum continued with persistence of
      infection. These findings have important implications for diagnosis, as well as
      for both chemotherapy and development of vaccine strategies.'

PMID- 14593590
TI  - Nosocomial Mycobacterium bovis-bacille Calmette-Guerin infections due to
      contamination of chemotherapeutics: case finding and route of transmission.
AB  - We studied nosocomial infections due to Mycobacterium bovis bacille Calmette
      Guerin (BCG) Onco-TICE bacteria, transmitted by contamination of medication
      prepared in BCG Onco-TICE-contaminated hoods in the pharmacy, in 5
      immunocompromised patients at 3 hospitals. The BCG strains cultured from the
      patients had the same DNA profile as the BCG Onco-TICE strain used for bladder
      instillation. To prevent these infections, a change from open to closed
      preparation was made; strictly separated preparation in time of BCG Onco-TICE
      instillation and chemotherapy was enforced, the biological safety cabinet was
      disinfected between preparations, and gloves were changed between preparations.

PMID- 14593591
TI  - Decline in varicella-zoster virus (VZV)-specific cell-mediated immunity with
      increasing age and boosting with a high-dose VZV vaccine.
AB  - The safety and immunogenecity of a booster dose of live attenuated varicella
      zoster virus (VZV) vaccine was evaluated in 196 healthy subjects, >or=60 years
      old, who had already received a VZV vaccine >5 years before. This repeat booster
      dose was well tolerated. Cell-mediated immunity (CMI) to VZV was measured by an
      interferon-gamma (IFN-gamma) enzyme-linked immunosorbent spot-forming cell
      (ELISPOT) assay and a limiting dilution responder cell frequency (RCF) assay.
      Prevaccination responses decreased as a function of increasing age but were
      detectable in all subjects by use of the IFN-gamma ELISPOT assay. In most
      subjects, VZV-specific CMI was increased at 6 weeks postvaccination. The
      magnitude of the vaccine-induced IFN-gamma ELISPOT response was inversely related
      to prevaccination values. Although there was a significant correlation between
      the IFN-gamma ELISPOT and RCF assays, the ELISPOT assay had greater sensitivity
      and a wider dynamic range. A live attenuated VZV vaccine is safe and immunogenic
      in an elderly population, and the vaccine-induced immunity may be monitored by
      the IFN-gamma ELISPOT assay.

PMID- 14593592
TI  - Polymerase chain reaction for detection of herpes simplex virus (HSV) DNA on
      mucosal surfaces: comparison with HSV isolation in cell culture.
AB  - This study compared the rate of isolation of herpes simplex virus (HSV) from
      >36000 samples of mucosal secretions obtained from 296 HSV-infected persons
      versus the rate of detection of HSV DNA, by means of a real-time quantitative
      polymerase chain reaction (PCR) assay. Overall, HSV was isolated in 3.0% of
      samples, and HSV DNA was detected in 12.1% of samples. The mean number of HSV DNA
      copies was 10(4.9) in samples obtained on days when HSV lesions were present and
      10(4.4) in samples from days when HSV lesions were absent. There was a linear
      relationship between the ability to isolate virus in culture and the log number
      of copies of HSV DNA in the sample; this relationship persisted in samples from
      men or women, in samples from human immunodeficiency virus-negative or -positive
      participants, and in samples obtained on days when lesions were present or
      absent. In home-collected specimens, the ratio of PCR positivity to viral-culture
      positivity rose from 3.8:1 in the winter to 8.8:1 in the summer months,
      reflecting the lability of viral-culture specimens transported during warm
      weather.

PMID- 14593593
TI  - Variation of human herpesvirus 7 shedding in saliva.
AB  - Sequential analysis of human herpesvirus 7 (HHV-7) shedding in saliva obtained
      from healthy adults was performed for 6 months; virus was isolated in 92 (34.1%)
      of the 270 saliva samples obtained. Frequency of HHV-7 shedding in serially
      obtained saliva samples varied among subjects. Associations between frequency of
      HHV-7 shedding and age, sex, and virus antibody titer were analyzed, and,
      although sex was not associated with frequency of shedding, young age (P=.031)
      and low antibody titer (P=.006) were correlated with frequent viral shedding (5
      or 6 times/6 months).

PMID- 14593594
TI  - Assessment of development of resistance to antivirals in the ferret model of
      influenza virus infection.
AB  - We attempted to develop in vivo resistance of influenza virus to amantadine and
      to zanamivir, by use of the ferret model of influenza virus infection. Resistance
      of influenza virus A/LosAngeles/1/87 (H3N2) to amantadine was generated within 6
      days, during a single course of treatment, and mutations in the M2 gene that are
      characteristic of human infections were observed. In contrast, during an
      identical single course of treatment with zanamivir, no evidence of reduced
      susceptibility was demonstrated. Pooled virus shed by zanamivir-treated ferrets
      was used to infect another group of ferrets. Twenty virus clones grew in plaque
      assays containing zanamivir, indicating possible reduced susceptibility; however,
      none exhibited reduced susceptibility to zanamivir in neuraminidase (NA)
      inhibition assays. Sequencing of the NA gene of these clones revealed only a
      noncoding nucleotide mutation at position 685. Sequencing of the hemagglutinin
      gene revealed mutations at positions 53, 106, 138, 145, 166, and 186. Similar to
      the situation in humans, amantadine use in ferrets rapidly produces antiviral
      resistance, but zanamivir use does not, although nucleotide changes were
      observed.

PMID- 14593595
TI  - Cross-reactive H1N1 antibody responses to a live attenuated influenza vaccine in
      children: implication for selection of vaccine strains.
AB  - Cross-reactive antibody responses of 3 trivalent, live attenuated intranasal
      influenza vaccine (FluMist) formulations containing 3 different H1N1 strains
      (A/Texas/36/91, A/Shenzhen/227/95, and A/Beijing/262/95) were evaluated in
      initially seronegative children. FluMist containing A/Shenzhen/227/95 was more
      likely to induce cross-reactive hemagglutination inhibition (HAI) antibody
      against A/Texas/36/91 than against A/Beijing/262/95, and FluMist containing
      A/Beijing/262/95 induced low levels of cross-reactive HAI antibody against
      A/Shenzhen/227/95 and A/New Caledonia/20/99. The observed differences in HAI
      cross-reactivity seem to be partly related to the number of amino acid (aa)
      differences on the hemagglutinin 1 domain (328 aa residues) rather than the
      hemagglutinin protein (550 aa residues).

PMID- 14593596
TI  - Genetic heterogeneity of the NS5A gene of hepatitis C virus and early response to
      interferon-alpha.
AB  - The double-stranded RNA-activated protein kinase-binding domain (PKRbd) of the
      NS5A gene of hepatitis C virus (HCV) was studied by the cloning and sequencing
      method, in HCV-infected patients who had a primary resistance to treatment with
      interferon (IFN)-alpha (early nonresponders). Patients whose virus load decreased
      by >or=0.5 log (early responders) were similarly analyzed. In the 2 groups, the
      PKRbd evolved similarly over the first 24 h. Selection of resistant HCV variants
      is unlikely to explain primary resistance to IFN-alpha.

PMID- 14593597
TI  - Prospects for elimination of bancroftian filariasis by mass drug treatment in
      Pondicherry, India: a simulation study.
AB  - LYMFASIM, a microsimulation model for transmission and control of lymphatic
      filariasis, was used to simulate the effects of mass treatment, in order to
      estimate the number of treatment rounds necessary to achieve elimination.
      Simulations were performed for a community that represented Pondicherry, India,
      and that had an average precontrol microfilariae (MF) prevalence of 8.5%. When
      ivermectin was used, 8 yearly treatment rounds with 65% population coverage gave
      a 99% probability of elimination. The number of treatment rounds necessary to
      achieve elimination depended to a large extent on coverage, drug efficacy, and
      endemicity level. Changing the interval between treatment rounds mainly
      influenced the duration of control, not the number of treatment rounds necessary
      to achieve elimination. Results hardly changed with alternative assumptions
      regarding the type of immune mechanism. The potential impact of mass treatment
      with a combination of diethylcarbamazine and albendazole is shown under different
      assumptions regarding its efficacy. Human migration and drug resistance were not
      considered. Results cannot be directly generalized to areas with different vector
      or epidemiological characteristics. In conclusion, the prospects for elimination
      of bancroftian filariasis by mass treatment in Pondicherry seem good, provided
      that the level of population coverage is sufficiently high.

PMID- 14593599
TI  - Association of mannose-binding lectin polymorphisms with sepsis and fatal
      outcome, in patients with systemic inflammatory response syndrome.
AB  - Genetic factors may predispose critically ill patients to increased risk of
      developing sepsis. Mannose-binding lectin (MBL) is an important factor in innate
      immune defense. We investigated whether MBL gene polymorphisms causing low levels
      of MBL are associated with the development and progression of sepsis in adult
      patients in intensive care units. In 272 prospectively monitored patients with
      systemic inflammatory response syndrome, different MBL genotypes were compared,
      with respect to microbiology, sepsis development, and survival. The presence of
      MBL variant alleles was associated with the development of sepsis, severe sepsis,
      and septic shock. An increased risk of fatal outcome was observed in patients
      carrying variant alleles. These data show that MBL insufficiency plays an
      important role in the susceptibility of critically ill patients to the
      development and progression of sepsis and confers a substantial risk of fatal
      outcome.

PMID- 14593598
TI  - Protective efficacy of CAP18106-138-immunoglobulin G in sepsis.
AB  - Naturally present antibacterial proteins play an important role in innate host
      defense. A synthetic peptide mimicking the C-terminal lipopolysaccharide (LPS)
      binding domain of rabbit cathelicidin CAP18 was coupled to immunoglobulin (Ig) G
      to create CAP18(106-138)-IgG, a construct that, in concentrations equimolar to
      those of peptide alone, binds and neutralizes LPS and kills multiple gram
      negative bacterial strains. The protective efficacy of CAP18(106-138)-IgG was
      evaluated in a model of cecal ligation and puncture in mice. A single intravenous
      administration of 20 mg/kg CAP18(106-138)-IgG protected against mortality,
      compared with sham-coupled IgG (P<.03). There was no protection offered by
      administration of equimolar peptide alone (P=.96). There was a trend toward
      protection in C3H/HeJ mice that are minimally sensitive to LPS (P=.06),
      suggesting that direct detoxification of LPS was not the only mechanism of
      protection. Chemical or genetic coupling of antimicrobial peptides to IgG may be
      a means of using these peptides to treat infections.

PMID- 14593600
TI  - [New trails in diabetology].

PMID- 14593601
TI  - [Diabetes].

PMID- 14593602
TI  - [Protein synthesis starts in the nucleus].

PMID- 14593603
TI  - [Scrapie, proteasome and endoplasmic reticulum].

PMID- 14593604
TI  - [Zebrafish, a model for migration of cancer cells?].

PMID- 14593605
TI  - [Cellular prion protein: more than what beyond spongiform encephalopathies].

PMID- 14593606
TI  - [Dorsal closure, forces for morphogenesis].

PMID- 14593607
TI  - [Beta-catenin and cell proliferation in normal and transformed intestinal cells].

PMID- 14593608
TI  - [Antibody diversity is endless!].

PMID- 14593609
TI  - [Dyskeratosis congenita: who is guilty?].

PMID- 14593610
TI  - [ATP synthase and apolipoprotein synthase: new players in atherosclerosis].

PMID- 14593611
TI  - [Adipocytokins, obesity and development of type 2 diabetes].
AB  - Normal metabolic balance is maintained by a complex homeostatic system involving
      multiple tissues and organs. Acquired or inherited defects associated to
      environmental factors in any part of this system can lead to metabolic disorders
      such as the syndrome X which is presently a frequent syndrome in industrialized
      countries. It is characterized by a cluster of risk factors of atherosclerosis
      including insulin resistance, hyperinsulinemia, impaired glucose tolerance or
      type 2 diabetes, hypertension, dyslipidemia, and coagulation abnormalities. Its
      pathophysiology is likely to involve insulin resistance at the level of both
      skeletal muscle and visceral adipose tissue and altered fluxes of metabolic
      substrates between these tissues that in turn impair liver metabolism.
      Therapeutic intervention favours at present diet and exercise prescriptions. In
      addition, if necessary, specific treatment of the metabolic disorders is
      required. In the treatment of insulin resistance, new promising drugs are likely
      to be used in the next future. In this regard, adipose tissue, once thought to
      function primarily as a passive depot for the storage of excess lipid, is now
      understood to play a much more active role in metabolic regulation, secreting a
      variety of metabolic hormones and actively functioning to prevent deleterious
      lipid accumulation in other tissues and to modulate the insulin resistance. Here,
      we review new advances in our understanding of mechanisms leading to insulin
      resistance and type 2 diabetes from the perspective of the role and interactions
      of recently identified adipocyte-specific chemical messengers, the
      adipocytokines, such as adiponectin, tumor necrosis factor-alpha, interleukin 6,
      and resistin.

PMID- 14593613
TI  - [Contribution of free fatty acids to impairment of insulin secretion and action:
      mechanism of beta-cell lipotoxicity].
AB  - Type 2 diabetes is characterized by two major defects: a dysregulation of
      pancreatic hormone secretion (quantitative and qualitative--early phase,
      pulsatility--decrease of insulin secretion, increase in glucagon secretion), and
      a decrease in insulin action on target tissues (insulin resistance). The defects
      in insulin action on target tissues are characterized by a decreased in muscle
      glucose uptake and by an increased hepatic glucose production. These abnomalities
      are linked to several defects in insulin signaling mechanisms and in several
      steps regulating glucose metabolism (transport, key enzymes of glycogen synthesis
      or of mitochondrial oxidation). These postreceptors defects are amplified by the
      presence of high circulating concentrations of free fatty acids. The mechanisms
      involved in the <<diabetogenicity>> of long-chain fatty acids are reviewed in
      this paper. Indeed, elevated plasma free fatty acids contribute to decrease
      muscle glucose uptake (mainly by reducing insulin signaling) and to increase
      hepatic glucose production (stimulation of gluconeogenesis by providing cofactors
      such as acetyl-CoA, ATP and NADH). Chronic exposure to high levels of plasma free
      fatty acids induces accumulation of long-chain acyl-CoA into pancreatic beta
      cells and to the death of 50 % of beta-cell by apoptosis (lipotoxicity).

PMID- 14593612
TI  - [Pharmacology of PPARalpha, PPARgamma and dual PPARalpha/gamma agonists in
      clinical development].
AB  - Cardiovascular diseases (CVD) remain the leading cause of mortality in the
      western societies. Several risk factors predispose to CVD including diabetes,
      obesity, insulin resistance, dyslipidemia and hypertension. Various
      pharmacological therapies have been developed to control the risk factors
      associated to CVD. Fibrates are able to correct dyslipidemia, therefore
      decreasing CVD risk. Thiazolidinediones (TZD) or glitazones by increasing insulin
      sensitivity decrease plasma glucose levels in diabetic patients. Both fibrates
      and TZD activate the peroxisome proliferator-activated receptors (PPARs), a
      family of nuclear receptors that play a central role in the control of lipid and
      glucose metabolism. In this review, we will discuss the mode of action of
      fibrates and TZD and we will present an overview on PPAR ligands under
      development.

PMID- 14593614
TI  - [Insulin signaling: mechanisms altered in insulin resistance].
AB  - Insulin has a major anabolic function leading to storage of lipidic and glucidic
      substrates. All its effects result from insulin binding to a specific membrane
      receptor which is expressed at a high level on the 3 insulin target tissues:
      liver, adipose tissue and muscles. The insulin receptor exhibits a tyrosine
      kinase activity which leads, first, to receptor autophosphorylation and then to
      tyrosine phosphorylation of substrates proteins, IRS proteins in priority. This
      leads to the formation of macromolecular complexes close to the receptor. The two
      main transduction pathways are the phosphatidylinositol 3 kinase pathway
      activating protein kinase B which is involved in priority in metabolic effects,
      and the MAP kinase pathway involved in nuclear effects, proliferation and
      differentiation. However, in most cases, a specific effect of insulin requires
      the participation of the two pathways in a complex interplay which could explain
      the pleiotropy and the specificity of the insulin signal. The negative control of
      the insulin signal can result from hormone degradation or receptor
      dephosphorylation. However, the major negative control results from
      phosphorylation of serine/threonine residues on the receptor and/or IRS proteins.
      This phosphorylation is activated in response to different signals involved in
      insulin resistance, hyperinsulinism, TNFalpha or increased free fatty acids from
      adipose tissue, which are transformed inside the cell in acyl-CoA. A deleterious
      role for molecules issued from the adipose tissue is postulated in the resistance
      to insulin of the liver and muscles present in type 2 diabetes, obesity and
      metabolic syndrome.

PMID- 14593615
TI  - [Hyperglycemia and angiogenesis].
AB  - Vascular complications of chronic hyperglycemia cause most of diabetes-associated
      morbidity and mortality. Main targets of chronic hyperglycemia are vascular
      endothelial cells. Ischemia is the late consequence of vascular damage in
      patients with diabetes and triggers an angiogenic response. In patients with
      diabetes, the angiogenic response to chronic ischemia can be excessive in some of
      the target organs and insufficient in others, in the same individual. The direct
      effects of hyperglycemia on the expression level of vascular growth factors have
      been variably appreciated and depend on the studied organ and model. Beyond the
      described effects of hyperglycemia on the expression level of vascular growth
      factors, direct and indirect effects of hyperglycemia on endothelial cell
      proliferation, extra-cellular matrix and metalloproteases might be involved in
      the pathology of angiogenesis in diabetes.

PMID- 14593616
TI  - [Transmitted beta-cell dysfunction as a cause for type 2-diabetes].
AB  - The pathways that control insulin release and regulate pancreatic beta-cell mass
      are crucial on the development of type 2 diabetes mellitus. Maturity-onset
      diabetes of the young comprises a number of single-gene disorders affecting beta
      cell development and/or function. A genetic basis for the more common forms of
      type 2 diabetes which affect adults in developed as well as many developing
      countries is less clear cut. It is also characterized by abnormal beta-cell
      function. Appropriate inbred rodent models are an essential tool for the
      identification of genes and environmental factors that increase the risk of type
      2 diabetes. The informations available from studies in the Goto-Kakizaki (GK) rat
      are here reviewed in such a perspective. This model was obtained by selective
      breeding of individuals with mild glucose intolerance from a non-diabetic Wistar
      rat colony. Heritability of defective beta-mass and beta-cell function in GK
      model is proposed to reflect the complex interactions of three pathogenic
      players: (1) three independent loci containing genes causating impaired insulin
      secretion; (2) gestational metabolic (hyperglycaemic) impairment inducing a
      programming of endocrine pancreas (decreased beta-cell mass) which is transmitted
      to the next generation; (3) secondary (acquired) loss of beta-cell
      differentiation due to chronic exposure to hyperglycaemia (glucotoxicity). A
      better understanding of the mechanisms involved in the failure of beta-cell
      function in the GK model will lead to identification of new therapeutic targets
      for both the prevention and treatment of type 2 diabetes.

PMID- 14593617
TI  - [MODY, a model of genotype/phenotype interactions in type 2 diabetes].
AB  - Maturity onset diabetes of the young (MODY) is a subtype of familial diabetes
      mellitus characterised by early onset, autosomal dominant inheritance and primary
      defects of insulin secretion. Mutations in six known genes (the enzyme
      glucokinase and five transcription factors expressed in pancreatic beta-cells)
      cause most of the MODY cases. This genetic heterogeneity is associated with
      metabolic and clinical heterogeneity making MODY an interesting model of
      genotype/phenotype interaction in diabetes.

PMID- 14593618
TI  - [Gluco-incretin hormones in insulin secretion and diabetes].
AB  - Nutrient ingestion triggers a complex hormonal response aimed at stimulating
      glucose utilization in liver, muscle and adipose tissue to minimize the raise in
      blood glucose levels. Insulin secretion by pancreatic beta cells plays a major
      role in this response. Although the beta cell secretory response is mainly
      controlled by blood glucose levels, gut hormones secreted in response to food
      intake have an important role in potentiating glucose-stimulated insulin
      secretion. These gluco-incretin hormones are GLP-1 (glucagon-like peptide-1) and
      GIP (gluco-dependent insulinotropic polypeptide). Their action on pancreatic beta
      cells depends on binding to specific G-coupled receptors linked to activation of
      the adenylyl cyclase pathway. In addition to their effect on insulin secretion
      both hormones also stimulate insulin production at the transcriptional and
      translational level and positively regulate beta cell mass. Because the glucose
      dependent insulinotropic action of GLP-1 is preserved in type 2 diabetic
      patients, this peptide is now developed as a novel therapeutic drug for this
      disease.

PMID- 14593620
TI  - [Children lead poisoning: what progress in 20 years?].

PMID- 14593619
TI  - [Nobel Prize 2002 for chemistry: mass spectrometry and nuclear magnetic
      resonance].
AB  - The Nobel Prize in Chemistry for 2002 has been awarded to two powerful
      spectroscopic methodologies through three valorous scientists, John Fenn and
      Koichi Tanaka, for mass spectrometry and Kurt Wuthrich for nuclear magnetic
      resonance. These techniques were previously known for their intensive use in
      chemical analysis. They are now developed at the chemistry/biology interface. Two
      new methods of soft ionization in mass spectrometry and a strategy of sequential
      assignment of nuclear magnetic resonance signals of biopolymers now allow the use
      of these powerful and complementary methodologies for the structural analysis of
      biological macromolecules, proteins, nucleic acids (DNA, RNA) and
      polysaccharides. Through the elucidation of their planar and three-dimensional
      structures and of the molecular mechanisms that govern their interactions, these
      techniques now may afford precious clues for understanding the molecular
      mechanisms of life.

PMID- 14593621
TI  - [Economic and socio-behavioural issues related to highly active antiretroviral
      therapies for HIV infection: the contribution of social science research].
AB  - This article presents a synthesis of the main topics covered by social science
      research (SSR) on HIV/AIDS, since the advent of highly active antiretroviral
      therapies (HAART) in 1996. SSR has shown that non-adherence cannot be reliably
      <<predicted>> on the sole basis of a few a priori patient characteristics that
      clinicians could easily identify before initiation of HAART, and that a dynamic
      approach to adherence, continuously monitoring the impact of patients' subjective
      experience with HAART is needed. In relationship with the evolution of HIV
      infection toward a <<chronic disease>>, SSR has dealt with the impact of HAART on
      all aspects of patients' daily lives (from employment and professional status to
      sexuality). It has also emphasised the potential contradictions between the hopes
      generated by these cost-effective therapeutic advances, on the one hand, and the
      high social vulnerability of a growing proportion of people living with HIV-AIDS,
      on the other hand. Finally, SSR suggests recommendations for <<normalising>> AIDS
      public policies without losing the potential for innovations that the fight
      against this epidemic has introduced in health care and <<Social Security>>
      systems, as well as physician-patient's relationships.

PMID- 14593622
TI  - [SARS-CoV: 1. The virus].

PMID- 14593623
TI  - [On misery coast. Episode 1: the market of vital drugs].

PMID- 14593624
TI  - [Women and strokes. Hospital epidemiology in Spain].
AB  - INTRODUCTION: Although in clinical practice no distinction is usually made in the
      prevention and management of strokes according to the sex of the patient, some
      studies suggest the existence of significant clinical differences in the strokes
      suffered by females. PATIENTS AND METHODS: The purpose of our study was to
      confirm and characterize these differences in patients admitted to hospitals in
      our community; to do so, we performed an analysis of the stroke or little stroke
      patients included in the Spanish Neurology Society's Stroke Database (BADISEN),
      from 1996 to 2001, belonging to eight Spanish hospitals. We analyzed the social
      aspects, risk factors, clinical features, diagnostic data, situation and referral
      on discharge of 4,248 female patients (39%). A univariate and, later, a
      multivariate analysis were performed using logistic regression of the variables
      that showed significant differences (p<0.2). RESULTS: The findings from our study
      confirm a number of differences between male and female stroke victims. Strokes
      occur later in females (71 years old compared with 69 in males), when the patient
      lives alone. The following also occur more frequently in these patients than in
      males: arterial hypertension (62.8 versus 51.9%, p<0.0001), cardiac insufficiency
      (8.0 as opposed to 4.5%, p<0.0001) and atrial fibrillation (21.4 versus 11.3%,
      p<0.0001) as risk factors; cardioembolic causation (22.4 against 15.4%, p<0.0001)
      in anterior circulation (44.0 compared to 36.1%, p<0.0001); severity is increased
      (6.8 on the Canadian scale versus 7.5%, p<0.0001); more medical complications
      (40.5 compared to 33.7%, p<0.0001), more serious sequelae (64.2 on the Barthel
      index compared to 72.9%, p<0.0001) and a higher institutionalization rate, among
      other distinguishing facts. CONCLUSIONS: Such differences must be taken into
      account in the prevention and management of strokes in females.

PMID- 14593625
TI  - [The psychoneurological status of newborn infants with congenital heart disease
      before surgical intervention].
AB  - AIMS: This study was conducted to evaluate, from a psychological and neurological
      point of view, the situation of newborn infants (NI) suffering from congenital
      heart disease before they are treated surgically. At the same time, we aimed to
      compare this group of patients with another group of children who were considered
      to be healthy. PATIENTS AND METHODS: Patients psychological development was
      evaluated using developmental landmarks from the Observational Scale of
      Development (OSD), which provides a percentage of elements acquired in different
      areas. Behaviour was evaluated by the observational recording of particular
      patterns of behaviour. The neurological study was based on a detailed neonatal
      examination, performed by people from the Child Neurology Section at our
      hospital, and which took into account the different behaviours displayed by the
      NI: reactive, grasping, communicative and affective. RESULTS: Findings show
      significant differences both in the psychological and neurological variables
      studied. They show how, generally speaking, healthy infants score higher in the
      areas of development that were evaluated than children suffering from heart
      disease. Likewise, lower average scores were observed in heart disease patients
      who require an early intervention, as compared with those who will be submitted
      to surgery later on. From the neurological point of view, a number of significant
      differences were found in their muscular activity. CONCLUSIONS: This analysis, a
      groundbreaker in the study of infants suffering from heart disease before their
      surgical intervention, shows how newborn infants who have been submitted to
      surgery in the neonatal period present a significant degree of hypotonia, a
      certain frailness and retardation in their motor development.

PMID- 14593626
TI  - [Combined supra and infratentorial presigmoideo approach for lesions of the
      petrous and clival regions].
AB  - INTRODUCTION: Petrous and petroclival lesions may be surgically treated with
      combinations of suprainfratentorial presigmoideo approach and microsurgical
      techniques. OBJECTIVE: To demonstrate the utility and to present our surgical
      experiences with this approach. PATIENTS AND METHODS: Thirteen patients with
      lesions of the clival, petrous region and of the cerebellopontine angle with
      extension toward the anterior portion of brainstem were taken to the operative
      room. There were nine women and four men. Eleven were adults and two children.
      The main clinical manifestations were headache (100%), dysfunction of cranial
      nerves (90%), ataxia (90%) hemiparesis (75%). There was papiledema in 45%.
      Petroclival meningiomas and schwannomas were the more frequent lesions. There
      were three patients with intraxial brainstem tumors and two arteriovenous
      malformations. There were not aneurysms. We performed nine retrolaberintic, three
      translaberintic and one transcochlear approach. RESULTS: There was not severe
      incapacity, vegetative or dead patients. The surgical complications were facial
      nerve paresis (31%), cerebrospinal fluid leak (23%), decreased gag reflex (15%),
      abducens nerve paresis, hemiparesis and Claude Bernard Horner syndrome (8%). 50%
      of these complications disappeared three months later. CONCLUSIONS: The
      suprainfratentorial presigmoidal approach and their surgical variations could be
      utilized to obtaining a low morbimortality, in the treatment of different
      neoplasm and vascular diseases of the petrous and petroclival region.

PMID- 14593627
TI  - [Multiple intracranial meningiomas].
AB  - AIMS: Multiple meningiomas is a condition in which the patient had more than one
      meningioma in several intracranial locations in the same patient without signs of
      neurofibromatosis. The incidence of multiple intracranial meningiomas varies from
      1 to 10% in different series. In this article we report our experience with the
      diagnosis and treatment of multiple meningioma. PATIENTS AND METHODS: The authors
      report 13 cases of multiple intracranial meningioma, consecutively operated on at
      our hospital between 1983-2003. All the patients were studied with CT and the
      last 10 with MRI. In 8 patients all of the tumours were found at the first
      admission. In the other five the diagnosis was not established until years after
      removal of the first meningioma. All the patients showed no manifestations of von
      Recklinghausen disease. RESULTS: The overall average age at diagnosis was 53.3
      years: 7 were females and 6 males. The predominant site for the meningioma was
      the parasagittal and falcine region, followed by the cerebral convexity. Thirty
      two meningiomas were treated with surgical extirpation and in four cases the
      treatment was radiotherapy. CONCLUSIONS: Multiple meningiomas are not a specific
      disease entity and have no distinctive clinical, pathological or surgical
      features. Despite the multiplicity of sites, multiple meningiomas do not differ
      in prognosis from benign solitary meningiomas.

PMID- 14593628
TI  - [Spastic tetraparesis as a sequela of bacterial meningitis].
AB  - AIMS: The aim of this study is to demonstrate the incidence of spastic
      tetraparesis (ST) in meningitis patients in the paediatric ICU, together with the
      associated variables, and establish comparisons with the existing literature.
      PATIENTS AND METHODS: We reviewed the medical records of patients who presented
      symptoms of meningitis and required hospital treatment in the Paediatric ICU at
      the Hospital de Clinicas de Porto Alegre, between January 1985 and June 2001. In
      addition to the diagnosis of meningitis and the incidence of ST as a
      complication, we also examined the aetiological agent, sex, age at the moment of
      hospital admittance, length of time spent in hospital and treatment given in each
      case. RESULTS AND DISCUSSION. An incidence of 15.1% was found for cerebral palsy
      in the 112 cases of bacterial meningitis that were followed up clinically. In the
      patients with ST, the time spent in hospital was longer, and the frequency of
      seizures, intracranial hypertension and the protein concentration levels in CSF
      were higher (p<0.05).

PMID- 14593629
TI  - [Peripheral and optical myeloneuropathy in a folic acid deficient alcoholic
      patient].
AB  - INTRODUCTION: In Western countries, neurological disorders secondary to toxic
      nutritional problems usually present as isolated cases that are generally
      associated to identifiable causes (alcoholism, eating disorders, absorption
      disorders, use of medicines) that reduce the availability of basic nutrients,
      especially B group vitamins, but also folic acid (FA). The optic nerves and the
      peripheral axons are frequent target organs in this type of pathology, but
      leukoencephalopathy and spinal cord involvement may also appear, often in
      combination. CASE REPORT: We describe the case of a 38-year-old female smoker
      with a heavy alcohol habit, who developed a subacute clinical pattern of,
      predominantly axonal, sensitive peripheral polyneuropathy, with vegetative fibre
      involvement. She also presented involvement of the posterior spinal cord, which
      gave rise to an ataxic disorder in the gait, as well as a severe bilateral
      retrobulbar optic neuropathy. Likewise, she presented macrocytosis (MCV: 118) due
      to megaloblastosis. She was also found to have a FA deficit but a normal vitamin
      B12 metabolism. With the help of supplementary vitamins, stopping drinking and
      the regularisation of her diet, the patient presented progressive clinical
      improvement, and was able to walk without support at 3 months and almost
      completely recovered her sight, which was corroborated by an improvement in the
      studies of both visual and somatosensorial evoked potentials. CONCLUSIONS: In our
      community, alcoholism is a frequent cause of nutritional deficiencies, which lead
      to neurological problems. FA is one of the nutrients that become deficient in
      alcoholics. More and more descriptions are being reported of peripheral
      polyneuropathy, retrobulbular optic neuropathy, myelopathy or leukoencephalopathy
      associated to FA deficiency, above all in patients with a history of alcoholism.

PMID- 14593630
TI  - [Overestimation of the degree of stenosis in the intracranial internal carotid
      artery determined by magnetic resonance angiography compared to conventional
      arteriography].
AB  - INTRODUCTION: In the evaluation of stenoses of the extracranial internal carotid
      artery (ICA), there are studies that suggest that magnetic resonance angiography
      (MRA) can be a substitute for conventional arteriography (CA), although it seems
      it has a tendency to overestimate the degree of stenosis. No similar comparison
      of the two techniques has been conducted in intracranial ICA. We report the case
      of a patient suffering from an acute ischemic stroke and symptomatic intracranial
      stenosis that was overestimated when MRA was used, compared to the results
      obtained using CA. CASE REPORT: We report the case of a 64-year-old male with a
      history of arterial hypertension, hypercholesterolemia and intermittent
      claudication who visited the emergency department because of the sudden onset of
      paresthesias in the left hemiface and hand. The cranial tomography scan performed
      in the emergency unit ruled out any acute bleeding or early signs of a stroke.
      Magnetic resonance (MR) diffusion imaging showed an acute ischemic stroke in the
      right parietal cortex. Extracranial MRA was normal and in the intracranial area a
      73% stenosis was detected in the cavernous segment of the right ICA, whereas the
      use of CA showed the stenosis to be only 55%. On repeating the MRA to rule out a
      possible rechanneling of the ICA, the image obtained was exactly the same as the
      earlier one. CONCLUSIONS: Our observations suggest that, as occurs with the
      extracranial part, MRA tends to magnify the degree of stenosis in the
      intracranial vessels, and this technique would therefore appear to be less
      efficient than CA in the evaluation of intracranial stenoses.

PMID- 14593631
TI  - [Ring chromosome 20, hypersensitivity to valproate and hyperammonemic
      encephalopathy].
AB  - INTRODUCTION: Ring chromosome 20 syndrome (C20A) is characterised by mental
      retardation, behavioural disorders, dysmorphias and refractory epilepsy with
      polymorphic seizures. It should therefore be treated with broad-spectrum
      antiepileptic drugs (AEDs), such as valproate (VPA) and topiramate (TPM). The
      relatively frequent hypersensitivity reactions to aromatic AEDs, not to VPA, the
      hyperammonemic encephalopathy (HAE) caused by the combination of VPA and TPM and
      the chromosome disorder described, affecting the same patient, do not appear in
      the literature we reviewed. CASE REPORT: A patient aged 5 years who, at the age
      of 11 months, was seen to have psychomotor retardation, microcephaly,
      plagiocephaly, facial dysmorphia and hypotonia. At 26 months, the patient
      presented seizures with fever, sucking, perioral cyanosis, clonisms in the upper
      extremities and hypotonia. Karyotype: C20A, with no mosaicism. Treatment was
      started with VPA up to 600 mg/day, and moderate eosinophilia appeared from 450
      mg/day onwards. At the age of 4 years, the patient suffered partial complex
      seizures, which stopped with the addition of TPM. At the same age there was also
      anorexia, loss of weight, adynamia, hypotonia, drowsiness, confusion, increased
      eosinophilia (20.3%) and IgE and a rash caused by the VPA. The clinical features
      yielded on adding dexchlorpheniramine. Nine months later, apathy, adynamia,
      eosinophilia and hyperammonemia reappeared; we therefore reduced and later
      stopped administration of VPA, although TPM was maintained. CONCLUSIONS: No
      relation between hypersensitivity to VPA, HAE and C20A has been described. The
      VPA TPM combination was effective, but in the end we had to stop administering
      VPA because of hypersensitivity and the side effects (HAE) of the combination.

PMID- 14593632
TI  - [Acute infantile hemiplegia caused by Coxsackie B virus].
AB  - INTRODUCTION: Acute infantile hemiplegia (AIH) is a syndrome that appears,
      typically, in infants without any underlying neurological damage. It can be due
      to a number of causes, in which viral infections play an important role. We
      report a case of AIH caused by Coxsackie B virus. CASE REPORT: A 20-month-old
      female who visited because of fever, vomiting and progressive left hemiparesis.
      Clinical exploration did not reveal any alteration in the level of consciousness
      and the only striking feature was the left hemiparesis, with weak deep muscle
      reflexes. Of the complementary examinations carried out, the most important were:
      LCR with 80 leukocytes/mm3 (predominance of mononuclear cells), EEG with a
      persistent focus in the right temporal region (which had become normal at four
      days) and a positive Coxsackie B virus serology. Progression was completely
      normal. CONCLUSIONS: AIH is produced as a complication of focal encephalitis
      which gives rise to a vasculitic phenomenon. Among the infectious causes, one
      important aetiological agent is the herpes simplex virus. Enterovirus, however,
      are infrequent. Therefore, until the exact aetiology has been established, it
      appears wise to begin empirical therapy with acyclovir. When the germs involved
      in this entity are enterovirus, prognosis is good, although there are reports of
      cases involving neurological sequelae in the literature.

PMID- 14593633
TI  - [Critical period of cortical plasticity].
AB  - INTRODUCTION AND DEVELOPMENT: Alterations of sensory experience cause large-scale
      re-arrangements of cortical connectivity only early in life. After a critical
      period that roughly ends by puberty, comparable modifications requires more
      invasive manipulations, including deafferentation and cortical lesions. At a
      cellular level, the elementary mechanisms responsible for synaptic modification
      appear to be available throughout life. Thus, in adults, experience dependent
      plasticity might be constrained additional factors, like the maturation of
      inhibition or changes in the extra cellular matrix. Such view is consistent with
      a limited, but not absent, modifiability of adult cortical circuits. This view
      also has interesting therapeutical implications. CONCLUSION: In this scenario,
      manipulation of these limiting factors, for example reducing synaptic inhibition,
      might be a useful strategy to enhance plasticity and to restore function in the
      adult cortex.

PMID- 14593634
TI  - [Non-convulsive status epilepticus].
AB  - DEVELOPMENT: Non-convulsive status epilepticus (NCSE) is an epileptic condition
      lasting more than 30 minutes in which continuous or recurrent seizure activity on
      the electroencephalogram (EEG) is responsible for diverse clinical symptoms
      including alteration of mental state, abnormal behaviour, perception disturbances
      or consciousness impairment. Most authors recognize two types of NCSE depending
      on the ictal electroencephalographic changes: generalized (absence status
      epilepticus) and complex partial status epilepticus (CPSE). In addition, there is
      also a simple form of partial status which is likely underdiagnosed because of
      its frequent progression to CPSE, subtle and varied symptomatology and high
      proportion of normal electroencephalograms (EEG). Absence status epilepticus
      (ASE) may occur in different clinical situations including idiopathic generalized
      epilepsy (typical AS), symptomatic generalized epilepsy (atypical AS), and
      elderly subjects without antecedents of epilepsy on chronic treatment with
      psychotropic drugs (de novo AS of late onset). Furthermore, CPSE is more frequent
      than previously mentioned. Although initially was equated with temporal lobe
      status epilepticus, extratemporal cases of CPSE have been well-documented, and
      the electroclinical characteristics of two types (I and II) of frontal CPSE have
      been recently described. NCSE may occur in patients with diverse clinical
      diagnosis such as hypoxic-anoxic encephalopathy, cancer, drugs, autoimmune
      disorders, Creutzfeldt-Jakob disease, chromosomal alterations, peritoneal
      dialysis, infections, cerebral hamartomas or head trauma. CONCLUSION: The
      identification of NCSE may be particularly arduous and, therefore, a high level
      of suspicion is essential to obtain an early diagnosis. An urgent EEG with
      administration of intravenous benzodiazepines is considered as the method of
      choice in the diagnostic evaluation of NCSE.

PMID- 14593635
TI  - [Bone marrow stromal cells. An alternative source of restorative therapy in
      degenerative diseases of the central nervous system].
AB  - AIMS: The aim of this study is to describe the capacity of bone marrow cells to
      limit or slow down the damage and chronic neuronal degeneration produced by
      degenerative diseases of the central nervous system (CNS), as well as the
      potential capacity of the method to provide other substances or genetic material.
      DEVELOPMENT: The search for new sources of cells that maintain the ability to
      divide and distinguish themselves from different cellular phenotypes opens up
      huge new opportunities in the restorative therapy of these clinical entities.
      Bone marrow cells, and especially stromal stem cells, have been seen to conserve
      a high capacity to distinguish and originate different strains of characteristic
      brain cells (neurons, astrocytes, and glial cells), and also the capacity to
      restore the population of stem cells when they are stimulated in a suitable
      fashion. CONCLUSIONS: Future experimental studies will be aimed at searching for
      new ways to enhance the composition, viability and differentiation of the cells
      to be implanted and will evaluate their effects on diseases of the CNS.

PMID- 14593636
TI  - [Clinical and neuropsychological characteristics of Huntington's disease: a
      review].
AB  - INTRODUCTION: Huntington's disease is a dominant autosomic neurodegenerative
      disorder. This article's objective is to provide an up-to-date description of the
      clinical and neuropsychological manifestations over the course of the disease.
      METHOD: According to clinical studies, the main characteristics of Huntington's
      disease include motor deficits, psychiatric problems and cognitive deficits. Many
      investigations have shown that a fronto-subcortical circuit dysfunction is
      responsible for these deficits. As the disease progresses, patients tend to have
      more cognitive difficulties which include attention/concentration problems,
      slowed cognitive processing, memory and language deficits, visuo-spatial problems
      and executive functioning difficulties. CONCLUSION: Studies with asymptomatic
      carriers of Huntington's disease have shown that cognitive deterioration may
      begin long before a clinical diagnosis of the disease is possible.

PMID- 14593637
TI  - [Diagnostic methodology in muscular pathologies].
AB  - AIMS: To analyse the different methodologies and their technical approaches, and
      compare the value and specificity of each of them in the diagnostic
      interpretation of muscular biopsies. DEVELOPMENT: Since the first descriptions by
      Duchenne in the 19th century, a series of stages for interpreting muscular
      biopsies crucial to the methodological approach were developed. The largest
      groups of muscular diseases (neurogenic atrophy, dystrophy and others), which
      were established on the basis of purely morphological studies, were later
      examined using histochemical techniques that allowed some diseases to be
      considered on an individual basis. One decisive factor in interpreting muscular
      biopsies and in diagnostic accuracy was the application of immunohistochemical
      techniques. The discovery of the gene responsible for Duchenne and Becker
      muscular dystrophies, and the later identification of dystrophin using reverse
      genetics, triggered off a series of events which led to the identification of
      various genes and proteins responsible for a number of muscular diseases. From
      that moment onwards it became possible to distinguish between previously
      undefined muscular dystrophies, e.g. different types of limb girdle dystrophy, to
      subclassify allelic diseases, such as Becker muscular dystrophy, and to identify
      carriers of X-linked diseases, for example. Ultrastructural examinations have
      also proved to be very useful. CONCLUSION: At present, the degree of diagnostic
      accuracy achieved in muscular pathologies is remarkable and the discoveries that
      have gradually been made have marked a series of stages, none of which has
      excluded the one preceding it and all of which are of great importance when it
      comes to interpreting a muscular biopsy.

PMID- 14593638
TI  - [Myofibrillar myopathies].
AB  - AIMS: The aim of this study is to analyse the different types of myopathies that
      are included under the name of filament pathologies and to review both their
      clinical, pathological and genetic aspects. DEVELOPMENT: The term filament
      pathologies embraces a heterogeneous group of diseases caused by mutations in the
      genes that code for the intermediate filaments. Myofibrillar myopathies or
      myopathies with desmin accumulation belong to the group of filament pathologies.
      Myofibrillar myopathies are clinically and genetically heterogeneous diseases,
      with common myopathological bases, which translate a process of myofibril
      degradation. One characteristic of these diseases is the presence of desmin
      immunoreactive inclusions in the cytoplasm of the muscle fibres. Approximately a
      third of the cases are due to mutations in the desmin gene, although to date
      mutations in the alpha-B-crystallin gene have been reported in two families. In
      the other patients the gene responsible for the disease remains unknown.
      CONCLUSION: The complexity of the so-called 'filament pathologies' calls for a
      multidisciplinary approach to the patient so that the myopathy can be correctly
      classified. This should consist in a clinical and neurophysiological examination,
      an immunohistochemical and electron microscope study of the muscle biopsy, and a
      genetic analysis to check for mutations in the desmin and the alpha-B-crystallin
      gene.

PMID- 14593639
TI  - [The laminopathy saga].
AB  - AIMS: Our aim was to clinically characterise Emery-Dreifuss muscular dystrophy,
      to differentiate the X-linked forms of inheritance from the forms involving
      autosomal dominant inheritance, from a genetic point of view, and to describe the
      phenotypical heterogeneity of mutations in the LMNA gene itself. DEVELOPMENT: We
      describe the identification of the mutations in the lamina A/C gene, the LMNA
      gene, which was made possible thanks to the networks allowing workers in
      different countries to collaborate. Mutations in this gene are responsible for
      autosomal dominant Emery-Dreifuss disease, as well as other diseases that are
      phenotypically very distinct, such as limb girdle muscular dystrophy associated
      with cardiac conduction defects (LGMD1B), dilated myocardiopathy with conduction
      defects (DCM-CD), Dunnigan-type familial partial lipodystrophy (FPLD) and,
      finally, an autosomal recessive form of axonal neuropathy or Charcot-Marie-Tooth
      disease type 2 (AR-CMT). CONCLUSIONS: Laminas are intermediate filaments that
      constitute the inner nuclear membrane of any cell and the mutations in the lamina
      A/C gene can give rise to such distinct clinical patterns as a kind of muscular
      dystrophy that is similar to the well known X-linked Emery-Dreifuss disease or a
      form of Charcot-Marie-Tooth-type neuropathy. Work is currently being conducted on
      an experimental animal model capable of providing us with a better understanding
      of the physiopathological mechanisms involved in the production of these tissue
      specific diseases, although they are due to mutations in a gene that codifies for
      proteins that are expressed all over.

PMID- 14593640
TI  - [Mitochondriopathies].
AB  - AIMS: The purpose of this study is to review different aspects of mitochondrial
      myopathies. DEVELOPMENT: Mitochondrial DNA is different to that found in the
      nucleus and is generally inherited through the mother. There are from 2 to 10
      copies per mitochondrion and hundreds or thousands of mitochondria per cell. It
      contains 37 genes. The oxidative phosphorylation system consists of five
      enzymatic complexes. Mitochondrial diseases can affect many organs but somewhat
      more frequent in tissues that are physiologically more demanding as regards
      oxidative phosphorylation, such as the nervous system, the heart and skeletal
      muscle. Diagnosis of mitochondrial disease is performed by studying skeletal
      muscle because it is easily accessible and because of its dependence on oxidative
      metabolism; moreover, deficits in the respiratory chain are often not expressed
      in cultivated fibroblasts. CONCLUSIONS: The bioptic muscle specimen must be
      frozen using isopentane for later histochemical examination. For study under the
      electron microscope, a small sample must be set in glutaraldehyde or a similar
      fixative. A 150 mg (5 mm3) fragment which has been frozen without isopentane
      should be used for the study of the respiratory chain, although fresh muscle
      tissue is needed for the examination of the complex V. About 50 mg of frozen
      tissue are required for the study of the mitochondrial mutations.

PMID- 14593642
TI  - [The role of the electron microscope in the study of muscular diseases].
AB  - AIMS: Our study examines the most significant aspects of electron microscopy in
      primary and secondary myopathies from the point of view of the day-to-day
      activity of a general ultrastructural diagnosis laboratory. DEVELOPMENT: We
      review cases of neuromuscular pathologies in which electron microscopy has
      contributed to greater accuracy in diagnosis or the understanding of the
      pathogenic process, and our own data were tested against the existing literature.
      CONCLUSIONS: As stated in several recent papers, our experience shows that
      electron microscopy is still a very important tool in the field of muscular
      diseases and can provide crucial diagnostic data, confirm the results obtained by
      other techniques or help settle the physiopathological foundations of many of
      these disorders.

PMID- 14593641
TI  - [Congenital myopathies].
AB  - INTRODUCTION: Congenital myopathies include many genetically distinct diseases
      which have in common the early appearance of symptoms and characteristic
      morphological findings. AIM: To resume clinical, pathological and genetic
      findings of the most frequent myopathies in this group. DEVELOPMENT: The most
      severe of these group is myotubular myopathy; affected boys die frequently in the
      neonatal period due to respiratory failure. The altered protein, myotubularin, is
      involved in the metabolism of PI3P. The gene mutated is in Xq28 and more than 140
      different mutations have been reported. Centronuclear myopathy is a genetically
      heterogeneous group, most frequently recessive but sometimes dominant and with a
      variable clinical course; childhood and adolescent cases usually present facial
      weakness and ophthalmoplegia together with proximal weakness, while adult forms
      show symptoms similar to limb girdle dystrophies. The protein responsible of the
      disease as well as the genetic locus involved are still unknown. Central core
      disease (CCD) is a scarcely progressive disease frequently associated with
      skeletal malformations. The inheritance is usually dominant. CCD has an important
      association with malignant hyperthermia and both diseases share the same gene in
      19q13, locus of the RYR1 gene which encodes the ryanodine receptor. Minicore
      myopathy is a recessive disorder which shows four different phenotypes, the most
      frequent being the 'classical' one, with axial weakness, scoliosis and severe
      respiratory insufficiency; some of these cases have mutations in the
      selenoprotein N gene. Other phenotype with slowly progressive weakness and hand
      atrophy has a homozygous mutation in the RYR1 gene. Nemaline myopathy shows four
      different clinical and genetic types according to the age of beginning of
      symptoms and the type of inheritance. Several different genes have been
      identified: TPM3 in 1q21, NEB in 2q21 22, ACTA1, TPM2 and TNNT1.

PMID- 14593644
TI  - [Posterior reversible leukoencephalopathy syndrome, pheochromocytoma and von
      Hippel-Lindau disease].

PMID- 14593643
TI  - [Epilepsy clinics].
AB  - AIMS: The current level of technological progress in the methods of diagnosis and
      treatment of epilepsies requires certain resources to be concentrated in so
      called epilepsy clinics (EC) or centres. DEVELOPMENT: Although many epileptic
      patients can be diagnosed and treated by clinicians who are not specialized in
      epilepsies, those whose diagnosis is not totally sure and those who do not have
      their seizures completely controlled should be referred to an EC. EC are
      stratified according to the degree of complexity of the studies and therapeutic
      measures carried out there, the most important being video-EEG monitoring and
      epilepsy surgery. Moreover, they can be both medical and medical-surgical EC, and
      may be basic or a reference in their field. If they are properly adapted to a
      certain volume of population by gradually meeting the local medical and social
      requirements until they reach an optimum level of development, they can be
      extremely effective and efficient. The different regional EC must be connected to
      one another and cooperate with common guidelines for action that have been
      commonly agreed to by all the centres. They must also allow a bidirectional flow
      of patients. Every EC must fulfil certain minimum requirements to guarantee the
      quality of the health care offered there. CONCLUSIONS: Doctors who attend people
      with epilepsy, with the support of the health authorities, must promote the
      setting up and development of EC, in order to achieve the maximum possible
      control over the seizures and a better quality of life for the epileptic patient.

PMID- 14593645
TI  - [Guillain-Barre syndrome. What should be done, when the treatment appears to
      fail?].

PMID- 14593646
TI  - Erratum regarding AED use in children.

PMID- 14593647
TI  - [Analysis of main functional parameters of the national system for mandatory
      social insurance against workmen's occupational risks].
AB  - The article covers first published main parameters of management and practical
      activities of national system for mandatory social insurance of workmen's
      occupational risks within a Federal Law No 125-FL "On mandatory social insurance
      against occupational accidents and diseases". The authors present dynamics of
      insurers (employers) registration, values of allocation rates, dynamics and
      structure of insurance payments, results of investigations on traumatism and
      occupational diseases. The suggestions are ways to improve the existing system
      from occupational medicine viewpoint.

PMID- 14593649
TI  - [Level, structure and dynamics of combined forms of occupational diseases among
      coal miners of Donetsk region].
AB  - The authors presented data on levels, structure and dynamics of combined
      occupational diseases in coal miners of Donetsk region in Ukraine, analyzed
      possible mechanisms of such diseases.

PMID- 14593648
TI  - [Some aspects of occupational spinal diseases].
AB  - Prevalence of neurologic cervical and lumbar disorders among workers does not
      depend upon hardness of work conditions. First diagnosed occupational vertebral
      syndromes were clinically divided into reflectory and compression ones. Length of
      service, age and X-ray signs appeared not to differ significantly between the
      groups.

PMID- 14593650
TI  - [Occupational risk and evaluation of health damage in workers engaged in
      organochlorine compound production].
AB  - The authors analysed structure and degree of occupational risk in chlorine
      organic compounds production, revealed a combination of chemical, physical
      hazards with work burden and determined the work conditions as harmful and
      dangerous (3.2-3.4). With consideration of most medical and biologic parameters,
      high level of occupational risk appeared to correspond to significant (from
      medium to nearly complete) occupational conditionality of the disorders
      diagnosed. The suggested and approved method to determine occupational
      conditionality of health disorders at hazardous work conditions could serve as a
      basis for occupational medical standard.

PMID- 14593651
TI  - [Features of psychologic adaptation and prevalence of border mental disorders
      among cargo vehicle drivers].
AB  - Studying features of psychic adaptation in 148 cargo transport drivers, the
      authors revealed high risk of boundary psychic disorders. Occupational research
      defined emotional and informational load characteristic for drivers and leading
      to exhaustion of adaptation and compensatory mechanisms. Factor dispersion
      analysis helped to determine leading role of occupational length of service--risk
      factor and indicator of psychic dysadaptation.

PMID- 14593652
TI  - [Metabolic disorders and their correction in petrochemical production workers
      exposed to heptyl].
AB  - The materials cover work conditions and health state of individuals working at
      major petrochemical enterprise and having occupational exposure to highly toxic
      hepatotropic chemicals including heptyl.

PMID- 14593653
TI  - [Main trends concerning risk factors and health of adolescents in Far North].
AB  - The actual problems of health-keeping in children and adolescents living in high
      latitudes are analyzed. The data on morbidity and spreading of risk factors of
      chronic non-infectious diseases in adolescents aged 14-17 living in the Far North
      are presented.

PMID- 14593654
TI  - [Calculating risk and relative genetic effects of some alkylating agents].

PMID- 14593655
TI  - [Population analysis of the immune status of immigrants in Far North].
AB  - In this article normative parameters of immune status of Nadym population of
      Yamalo-Nenets Autonomous Okrug are given. Type of immune status with moderate
      activation of cell part of immunity, humoral suppression and activation of non
      specific resistance was determined.

PMID- 14593656
TI  - [Functional features of cardiovascular and respiratory systems among immigrants
      of Far North].

PMID- 14593657
TI  - HIV and women in Hawaii: risk and protective factors in HIV/AIDS prevention.
AB  - Using semi-structured interviews with adults living with or at-risk for HIV and
      interviews and focus groups with key informants, the present study examined risk
      for HIV transmission among women living in Hawaii. Key research findings suggest
      that women in Hawaii are at risk for HIV infection primarily through sexual
      contact with their male sex partners, including bisexual and injection drug using
      (IDU) men. A significant factor in women's HIV risk is sex and gender role
      dynamics in the context of their relationships with men. Recommendations support
      primary prevention services for HIV-positive men who have sex with men and women,
      and IDU men who also have sex or share needles with women. Collaborative efforts
      between health care professionals and HIV/AIDS agencies to integrate gender
      specific and culturally appropriate HIV prevention interventions are recommended.

PMID- 14593658
TI  - Nursing workforce supply data trends in Hawaii.
AB  - Surveys of the nursing workforce in Hawaii over the last six years point to an
      increasing shortage of nurses. Data trends reveal a nursing workforce that is
      older than the rest of the U.S. with more ethnic and gender diversity. Strategies
      are needed to ensure adequate numbers and levels of nurses to meet the health
      care needs of the people of Hawaii.

PMID- 14593659
TI  - The role of community-based training in pediatric medical education at JABSOM.

PMID- 14593660
TI  - Increase in cancer rates among Filipino men in Hawaii.

PMID- 14593661
TI  - Changes in managed care activity in outpatient substance abuse treatment
      organizations, 1995-2000.
AB  - Using nationally representative data from 1995 and 2000, this study examines
      trends in managed care penetration and activity among outpatient drug treatment
      organizations in the United States. Further, it investigates how managed care
      activity varies across different types of treatment providers and for public and
      private managed care programs. Overall, managed care activity has increased, with
      a greater proportion of units having managed care arrangements and a larger
      percentage of clients covered by managed care. In general, public managed care
      activity has increased and private managed care activity has decreased. Treatment
      providers report that they have fewer managed care arrangements, which may
      reflect consolidation in the managed behavioral care sector. Finally, growth in
      managed care among outpatient substance abuse treatment units affiliated with
      hospitals and mental health centers may signal a preference for providers that
      can effectively link substance abuse treatment with medical and social service
      provision, or, alternatively, that linkages with such organizations may provide
      the size necessary to assume the risks associated with managed care contracts.

PMID- 14593662
TI  - The relationship between school characteristics and the availability of mental
      health and related health services in middle and high schools in the United
      States.
AB  - Problems related to mental illness are increasingly becoming the focal point of
      public concern over the safety and performance of schools, yet little is known
      about the availability and quality of school-based mental health services in the
      United States. In this article it is estimated that approximately 50% of US
      middle and high schools have any mental health counseling services available
      onsite and approximately 11% have mental health counseling, physical
      examinations, and substance abuse counseling available on-site. There are
      substantial differences in mental health counseling availability by region,
      urbanicity, and school size, with rural schools, schools in the Midwest and South
      regions, and small schools being least likely to offer mental health counseling.
      Multivariate estimates suggest that disparities between schools in the
      availability of mental health counseling and related health services may be
      partly explained by differences in access to Medicaid for financing of health
      services provided at school.

PMID- 14593663
TI  - Clinicians and outcome measurement: what's the use?
AB  - The goal of this study was to learn more about clinicians' experiences with, and
      perceptions of the utility, validity, and feasibility of standardized outcome
      measures in practice. Fifty randomly selected clinicians from multiple
      disciplines and multiple service agencies in a large children's public mental
      health service system were interviewed individually (n = 30) or in focus groups
      (n = 20) using semistructured interviews. There was great variability across
      clinicians in attitudes about empirical methods of treatment evaluation. There
      was consensus regarding feasibility challenges of administering standardized
      measures, including time burden and literacy barriers. Although all participants
      had received scored assessment profiles for their clients, the vast majority
      reported that they did not use the scores in treatment planning or monitoring.
      Their suggestions for improved clinical utility of outcome measurement are
      included. With increased attention and resources devoted to performance outcome
      assessment, it is concerning that most clinicians perceive little clinical
      utility of outcome measurement.

PMID- 14593664
TI  - Length of stay for psychiatric inpatient services: a comparison of admissions of
      people with and without developmental disabilities.
AB  - This study investigated associations between the presence of developmental
      disabilities and length of inpatient stay for mental health care. All psychiatric
      admissions of people with developmental disabilities over a 5-year period were
      selected (n = 294), and were compared using survival analysis to a random sample
      of admissions from the general psychiatric population (n = 287). Overall, people
      with developmental disabilities stayed in hospital longer than those without
      developmental disabilities, and this extra stay was partially attributed to
      casemix differences between the cohorts. Subanalysis in both cohorts showed that
      those going back to their usual living arrangement stayed a shorter period than
      those who were discharged elsewhere, and that people with developmental
      disabilities were less likely to be discharged to their usual living arrangement
      than were people without the disability. This study highlighted the importance of
      specialized residential and personal supports for people with developmental
      disabilities and a coexisting mental disorder.

PMID- 14593665
TI  - Mental health case management as a locus for HIV prevention: results from case
      manager focus groups.
AB  - HIV infection among people with severe mental illness (SMI) is a growing concern,
      and interventions have been designed to address HIV prevention among these
      individuals. However, little is known about the preparedness of mental health
      providers to support these interventions. This study concentrated on mental
      health case management as a locus for HIV-prevention services. Focus groups of
      case managers were conducted to learn participants' motivation to adopt HIV
      prevention services and barriers/facilitators to such adoption. Participants
      reported they would be motivated to offer HIV prevention if services were to be
      presented in the context of existing client relationships and case-management
      tasks. Barriers and facilitators were discussed at client, provider, and
      community levels, and recommendations for training were offered. Findings have
      implications for diffusion of HIV-prevention services in case management, and the
      line of questioning in focus groups provides a basis for learning about other
      behavioral health service contexts as loci for disease prevention.

PMID- 14593667
TI  - Medical versus nonmedical mental health referral: clinical decision-making by
      telephone access center staff.
AB  - A database review investigated decisions of clinicians staffing a university
      based telephone access center in referring new adult patients to nonpsychiatrists
      versus psychiatrists for initial ambulatory behavioral health care appointments.
      Systematically collected demographic and clinical data in a computer log of calls
      to highly trained care managers at the access center had limited predictive value
      with respect to their referral decisions. Furthermore, while 28% of the 610 study
      patients were initially referred to psychiatrists, billing data revealed that in
      person therapists soon cross-referred at least 20% more to a psychiatrist. Care
      managers sent 56% of callers already taking psychotropic medications to
      nonpsychiatrists, 51% of whom were then cross-referred to psychiatrists.
      Predictive algorithms showed no potential to enhance efficiency of decisions
      about referral to a psychiatrist versus a nonpsychiatrist. Efforts to enhance
      such efficiency may not be cost-effective. It may be more fiscally efficient to
      assign less-experienced personnel as telephone care managers.

PMID- 14593666
TI  - National spending on mental health and substance abuse treatment by age of
      clients, 1997.
AB  - This article examines 1997 national expenditures on mental health and substance
      abuse (MH/SA) treatment by 3 major age groups: 0-17, 18-64, and 65 and older. Of
      the total $82.4 billion in MH/SA expenditures, 13% went to children, 72% to
      adults, and 15% to older adults. MH/SA treatment expenditures made up 9% of total
      health care expenditures on children, 11% of total health care expenditures on
      adults, and 3% of total health care expenditures on older adults. Across the 3
      age groups, distinct differences emerged in the distribution of MH/SA
      expenditures by provider-type. For example, about 85% of spending for youth was
      for specialty MH/SA providers, compared to 76% for adults and 51% for older
      adults. In addition, 33% of MH/SA spending for older adults went to nursing home
      care, while other age groups had almost no expenditures in nursing homes. Age
      specific estimates enable policymakers, providers, and researchers to design
      programs and studies more appropriately tailored to specific age groups.

PMID- 14593668
TI  - Child functioning in rural and nonrural areas: how does it compare when using the
      service program site as the level of analysis?
AB  - The current study uses data from the national evaluation of the Comprehensive
      Community Mental Health Services for Children and Their Families Program to
      examine child functioning in rural (n = 8) as compared to nonrural (n = 18)
      system-of-care communities across the United States. In this study, the topic of
      rural versus nonrural differences is approached from a community-level
      perspective with aggregated functional impairment scores as the dependent
      variable of interest in weighted least squares regression. The demographic
      characteristics of children, particularly age, were more important predictors of
      functional impairment than geographic locale (i.e., rural vs nonrural).
      Specifically, while children served in nonrural communities were older than those
      served in rural communities, after controlling for this difference functional
      impairment levels were similar. It appears from these analyses that youth served
      in rural and nonrural communities with systems of care were more similar than
      they were different with regard to their level of functional impairment. This
      lack of aggregate functional difference between the rural and nonrural sites
      reminds policymakers and funding agents that youth in rural areas need equity in
      both access and resource for mental health services. As indicated by the findings
      in the current investigation youth in rural areas are not immune to the types of
      mental health challenges often publicized by researchers examining youth in
      nonrural areas.

PMID- 14593669
TI  - Agreement between CASA parent reports and provider records of children's ADHD
      services.
AB  - This study examines agreement between parental reports of children's ADHD
      outpatient services ascertained with the Child and Adolescents Services
      Assessment (CASA) and provider records among a sample of elementary school
      students who participated in an epidemiologically based health services study.
      Parental reports of any outpatient mental health treatment, services intensity,
      and medication regimens were compared to records of the specified mental health
      and primary care providers using intraclass correlations and kappa estimates.
      Results indicated that parental reports using the CASA produced valid data on
      whether any outpatient ADHD services had been received in the past 12 months (83%
      agreement), and on details of the child's medication regimens (kappas above
      0.90), but that agreement was poor on how many times the child had been seen
      (intraclass correlation 0.29), without agreement differences by provider type.
      These findings support the validity of using parental report for ADHD services in
      primary care settings and for study of medication regimens.

PMID- 14593670
TI  - [Histopathological and immunological analysis of hyperplastic palatine tonsils
      and adenoids in children with coexisting atopic dermatitis].
AB  - Allergic sensitisation of the airways occurs in the mucosa of the shock organ, or
      in the lymphatic stations draining these structures. The lymphatic structure
      closest to the nasal mucosa in humans is the adenoid and tonsils. Research done
      in respect to Waldeyer's ring on people dealing at the same time with allergy, is
      seldom the subject of dissertation in polish as well as world wide medical
      literature. In the enclosed dissertation, writers present the results of
      histopathological and immunohistochemical analysis of hyperplastic tonsils and
      adenoid, taken from children with coexisting atopy. The authors describe an
      immunohistochemical analyses of the hyperplastic human palatine tonsil. They
      present the expression of antigen CD3, CD20, CD45, CD68, EMA, SMA, Vimentin,
      Desmin, S-100, von Willebrand Factor, p35, Bcl-2, melanin, cytokeratin, estrogen
      receptor, progesteron receptor, kolagen IV and NSE in every region of pallatine
      tonsil. It is worthwhile to remark, that many of these cases, the presence of
      eosinophilia and subepithelial oedema was observed. Our immunohistochemical
      findings support the hypothesis that allergic sensitization takes place in the
      adenoid and tonsils. Furthermore, this study confirms that dendritic cells ad
      macrophages are involved and important in allergic disease.

PMID- 14593671
TI  - [Frequency of adenoid hypertrophy in children with allergic diseases].
AB  - Tonsils and adenoid are part of Waldeyer's ring, the basic function of which is
      antibody formation, they react later against a great variety of antigens. The
      role of enlarged adenoids and tonsils in upper airway obstruction has become well
      established earlier, thus, adenoidectomy with, or without, tonsillectomy is one
      of the most commonly performed surgical procedures in the paediatric population.
      Research done in respect to Waldeyer's ring on people dealing at the same time
      with allergy, is seldom the subject of dissertation in polish as well as world
      wide medical literature. To examine the influence of atopy on the adenoid
      hypertrophy we studied 115 children ages 4 to 9 years, with an average age of 5.9
      who had allergic rhinitis asthma or atopic dermatitis. The study suggested that
      allergic rhinitis is an important risk factor for an adenoid hypertrophy (AH) in
      children, therefore, early prevention of exposure to them may help reduce
      occurrence of AH.

PMID- 14593672
TI  - [Serum immunoglobulin E levels in relation to Waldeyer's ring surgery].
AB  - Tonsils and the adenoid are part of Waldeyer's ring, the basic function of which
      is antibody formation, they react later against a great variety of antigens.
      Tonsillectomy and adenoidectomy procedures are among the oldest surgical
      procedures still performed today. The different immunoglobulin serum levels in
      patients having undergone extirpation of the tonsils, adenoids or both, have been
      studied before and after surgery by different authors, with discordant results.
      Immunoglobulin E (IgE) is important in allergic reactions and host defense
      against parasites. In this study we measured serum levels of immunoglobulin E
      before and 3 months after tonsillotomy, adenoidectomy, and adenotonsillectomy.
      There were statistically significant differences between pre and post-operative
      levels of serum IgE, which decreased after tonsillotomy, but we have not noticed
      any statistically significant differences in the IgE values after adenoidectomy
      and adenoidotonsillotomy with respect to those prior to surgery.

PMID- 14593673
TI  - [Effect of cyclophosphamide on bone remodeling in rats].
AB  - Neoplasms, with or without metastases in bones, can induce pathological bone
      remodeling, leading to systemic bone resorption and hypercalcemia or osteomalacia
      and normocalcemia. The aim of the present study was to investigate the effect of
      a cytostatic--cyclophosphamide on the skeletal system in rats. The experiments
      were carried out in male Wistar rats with initial body weight of 212-229 g,
      divided into 3 groups (n = 6): I--Control, II--Cyclophosphamide (10 mg/kg m.c.
      i.m. daily for 14 days, and after a 7-day break, for 7 days), III-
      Cyclophosphamide (20 mg/kg m.c.p.o. daily for the initial 14 days). After 30 days
      of the experiment, the animals were killed and bone mass, length and diameter of
      long bones, mineral content in bones, transverse cross-section surfaces of the
      cortical diaphysis and of the marrow cavity, transverse growth, width of
      endosteal and periosteal osteoid in the tibia, width of trabeculae, width of
      epiphyseal cartilage and mechanical features of the femur were examined.
      Cyclophosphamide caused disorders of bone tissue remodeling. Decreases in bone
      mass, length, diameter, mineral content in bones, width of trabeculae in the
      femur, transverse growth, width of osteoid, transverse cross-section surface of
      the cortical diaphysis, and worsening of mechanical properties of the femur were
      observed.

PMID- 14593674
TI  - [Nickel allergy in contact and atopic dermatitis].
AB  - The study is aimed to determine the importance of type I and type IV allergy in
      eczema caused by allergy to nickel. The study was performed at 55 patients (42
      women, 13 men, aged 16-58 yrs) suffering from hand dermatitis (19 cases),
      disseminated eczema (22 cases) and atopic dermatitis (14 cases) with positive
      skin patch test to 2.5% nickel sulphate. In each patients history of illness was
      analyzed, total serum IgE level (tIgE) was estimated and specific IgE (sIgE) for
      nickel and also absolute blood eosinophils and basophils counts were estimated
      for the evaluation of the atopy features. In each patient patch skin test with
      different nickel sulphate dilutions were performed as well as skin prick tests
      with different dilutions of nickel sulphate. The following oral provocation tests
      were carried out with the nickel sulphate in doses 0.56 mg, 1.12 mg, 2.24 mg, 5.6
      mg and 11.2 mg. The test was stopped at the dose provoking the symptoms of
      illness. Positive family history, the increased tIgE serum level as well as
      absolute counts of eosinophils and basophils were present in some patients with
      atopic and contact dermatitis and they were not useful in differential diagnosis
      of this forms of skin allergy. Skin patch test with different concentrations of
      nickel sulphate was helpful to establish the degree of contact sensitivity in all
      patients. The oral provocation test with different dose of nickel sulphate also
      provoked symptoms in some patients in each observed groups, but the reaction to
      the lowest dose was observed only in patients with atopic dermatitis. Specific
      IgE to nickel as well as skin prick testing also with different dilutions of
      nickel sulphate are not useful in the diagnosis of nickel allergy. In the all
      examined patients they were negative. It seems that both types of allergy (type I
      and IV) may take part in the patho-mechanism of atopic and contact skin allergy
      with alternate prevalence of one of its depending on patient condition.

PMID- 14593675
TI  - [Pituitary tumors: hormonal status and immunohistochemical evaluation].
AB  - New imaging modalities and hormonal diagnostic improvement have markedly
      increased the number of newly recognized pituitary tumours. Introduction of
      immunohistochemical assays in histopathological diagnostics of pitutary adenomas
      resulted in better understanding of pathology and clinics of these neoplasms. The
      aim of the study was to correlate the hormonal status and hematoxylin-eosin
      staining results with immunohistochemical staining of pituitary tumours. The
      study included 40 patients aged 43.8 +/- 18.3 years, diagnosed with a pituitary
      tumour in the Department of Endocrinology Collegium Medicum UJ, who subsequently
      underwent trans-sphenoidal surgery in the Department of Neurosurgery Collegium
      Medicum UJ. The serum pituitary hormone levels were assessed by means of
      radioimmuno-assays. The surgically obtained tumour tissue was evaluated both by
      hematoxylin-eosin and immunohistochemical staining. Using traditional staining 33
      patients were diagnosed with chromophobic adenoma, 1 with basophilic adenoma, and
      remaining 6 with eosinophilic tumour. Immunohistochemical assays were ACTH
      positive in 16, TSH-positive in 7, GH-positive in 14 and PRL-positive in 17
      cases. In 15 subjects immunohistochemical staining was positive for at least two
      pituitary hormones. In 34 of 54 patients with positive immunohistochemical
      staining results, no increase in corresponding pituitary hormone serum levels was
      observed. In 5 of 9 patients with negative immunohistochemical staining, no
      increase in serum hormone level was noted, remaining 4 were characterized by
      hyperprolactinaemia. Tumour cells were ACTH-positive in 5 of 6 patients with
      elevated serum ACTH levels and GH- or TSH-positive in all cases of increased
      levels of these hormones. Only 6 of 15 subjects with hyperprolactinaemia revealed
      positive PRL immunohistochemical staining. CONCLUSIONS: Positive
      immunohistochemical staining often do not correlate with elevated basal serum
      pituitary hormone levels, which may be related to either impaired synthesis or
      excretion of the hormones by tumour cells. Increased serum levels of ACTH, TSH or
      GH are usually connected with positive immunohistochemical staining results.
      Hyperprolacinaemia in cases of PRL-negative assays arises from PRL secretion
      defects caused by the tumour presence itself.

PMID- 14593676
TI  - [Characteristics of physical activity among adults in Lodz: results of pilot
      study].
AB  - Regular physical activity of sufficient frequency, duration and intensity plays
      an important role in health promotion and prevention of cardiovascular and other
      chronic diseases. The aim of this study was to assess physical activity and
      capacity among adults in Lodz. This study was conducted in the group of 202
      people including 101 women and 101 men (mean age 44.9 +/- 11.6 years old).
      Physical activity was determined by the interviewer-administrated Seven-Day
      Physical Activity Recall (SDPAR). Physical fitness was determined among 50
      subjects by maximal oxygen uptake (VO2max) measured during submaximal exercise
      test according to indirect Astrand-Rhyming method. Total weekly energy
      expenditure in this group was 274.8 +/- 60.6 kcal/kg/wk. The proportion of
      moderate energy expenditure on sport activities in mean total weekly energy
      expenditure (kcal/kg/week) was 3.7%. Almost half of the subjects (46.0%) reported
      0.0 kcal/week energy expenditure on leisure time sport activities. The number of
      those who had from 1 to 499 kcal/week, 500 to 999 kcal/week, 1000 to 1999
      kcal/week, 2000 or more kcal/week energy expenditure on sport was only 9.0%,
      13.4%, 14.8%, 15.4% respectively. This study demonstrates that 70% of subjects
      did not achieve the level of physical activity recommended by experts in health
      promotion and prevention of cardiovascular and other chronic diseases.

PMID- 14593677
TI  - [Two diagnostic assays for serum procalcitonin measurement in clinical practice].
AB  - Procalcitonin (PCT) is a novel acute phase reactant useful in the diagnosis and
      monitoring of systemic bacterial infections. The aim of the study was to compare
      in clinical settings validity of two diagnostic methods for PCT determination.
      Serum PCT concentrations were measured by semiquantitative immunochromatographic
      test (PCT-Q) and immunoluminometric assay (ILMA)--LUMItest PCT in 192 serum
      samples. Results obtained by PCT-Q test were categorized into 4 groups: < 0.5
      ng/ml (n = 118); 0.5-1.9 ng/ml (n = 35); 2.0-9.9 ng/ml (n = 16); IV > or = 10
      ng/ml (n = 23); and compared with values measured by ILMA. In 130 cases (67.7%)
      measurements were identically categorized by both methods, in 56 samples (29.2%)
      results measured by ILMA were categorized within the next higher or lower
      category of the PCT-Q test and in 6 cases (3.1%) results were more aberrant.
      CONCLUSIONS: Immunochromatographic PCT-Q test is useful for the rapid, semi
      quantitative measurement of serum PCT concentration and can be used as a
      screening method in patients suspected of systemic bacterial infection. However
      the results of semi-quantitative test in comparison to ILMA method are not always
      identical. In doubtful cases, to get more accurate results and for the monitoring
      of treatment the ILMA method should be recommended.

PMID- 14593678
TI  - [Clinical and metabolic effects of recombinant human growth hormone in cardiac
      insufficiency].
AB  - Growth hormone (GH) acting through locally produced insulin--like growth factors
      stimulates myocardial hypertrophy and increases myocyte contractility. Many
      people with growth hormone deficiency (GHD) present a lower left ventricular
      mass, reduced ejection fraction and lower exercise tolerance. Recombinant human
      growth hormone (rhGH) administration gives a chance to correct these
      disturbances. On the other hand excessive levels of GH (for example in
      acromegaly) may induce heart failure too. Initially, cardiac hypertrophy is an
      adaptive response, but with time, in untreated cases, it leads to congestive
      heart failure. Mentioned information inclined many authors to undertake
      researches on rhGH application in severe heart failure in patient with idiopathic
      dilated cardiomyopathy and coronary disease. RhGH improved treatment let these
      patients reach heart transplantation.

PMID- 14593679
TI  - [Methods of prevention and reduction of delayed muscle soreness (DOMS)].
AB  - This review describes the methods of reducing the effects of delayed onset muscle
      soreness (DOMS) as a result of muscle contractions, including the cryotherapy,
      physical and pharmacological therapies. Concentric and eccentric exercise and
      some pharmacological agents are also described as the methods of DOMS prevention.

PMID- 14593680
TI  - [Is the brain a postmitotic organ? -- current knowledge on neural stem cells].
AB  - All the attempts for regeneration in the central nervous system (in clinical
      conditions) are still a failure. Hence the bulk of clinicists are convinced that
      the brain is a postmitotic organ. Are the pessimists right? In the recent few
      years some knowledge break-throughs have been made. It has been noticed in many
      places of adult mammals' brains there are cells capable of proliferating,
      including asymmetric divisions, and differentiating into neurons and glia when
      suitably stimulated. Such cells, called neural stem cells, are present also in
      the brains of adult humans, especially in the subventricular zone. It has been
      recently discovered that also cells derived from bone marrow are capable of
      differentiating into neurons. The authors reviewed world-wide literature devoted
      to this topic. They focused mainly on the biology of the newly discovered cells,
      and especially on their mitotic and differentiating potential. The authors
      critically assess the discoveries discussed.

PMID- 14593681
TI  - [Neural stem cells: perspectives of clinical application].
AB  - The prognosis for many patients with central nervous system (CNS) diseases has
      recently improved, especially due to enormous development of medical sciences.
      Nevertheless there are still pathologies very difficult to cure. It is caused
      mainly by the irreversibility of CNS lesions, that even after ceasing the primary
      pathological process--lead to deep functional deterioration. Hopefully this will
      change in the future thanks to the discovery of the stem cell population located
      in the CNS. These cells have to reproduce cytoarchitecture and CNS function. The
      range of possible use of the therapy based on neural stem cells (NSC) appears
      unlimited. The most advanced laboratory trials are focused on neurodegenerative
      diseases with very promising results The second field of clinical neuroscience
      that NSC can play a key role in are injuries of the CNS, with special emphasis on
      spinal cord injuries which are still an unresolved problem of neurotraumatology.
      Adding to the possible roles of NSC--they may act as transporters of transgenes
      in case of metabolic or neoplasmatic diseases. The interest of many groups of
      scientists in biological and clinical use of NSC appears to be justified. Authors
      present advancement and possible ways of development of therapeutic methods based
      on NSC.

PMID- 14593682
TI  - [Misdirected nerve regeneration: clinical implications].
AB  - Although peripheral nerve regeneration is not a precise renewal of primary
      connections, it often leads to successful return of their function. Moreover, in
      some cases, an injured nerve is aimly stitched to another one. A good example of
      such a procedure is intercostal neurotization of avulsed brachial plexus. Despite
      the fact that neural centers are not primarily suitable for their new function,
      they often fulfill it successfully. This respecification of function requires
      some changes in the central nervous system called "plasticity". Discussed are the
      potential mechanisms controlling these changes. The role of hypothetic proteins
      reversely transported from the target organ to the neuron's body, proprioceptive
      fibers and volitional control is mentioned. The punctual understanding of these
      mechanisms may appear not only very scientifically wonderful but also useful in
      clinical practice.

PMID- 14593683
TI  - [Cefepime: the new option of target antibiotic therapy].
AB  - Treatment of hospital infections caused by multidrugresistant pathogens like
      Pseudomonas, Acinetobacter, Enterobacter, Klebsiella needs microbiological
      monitoring from the beginning of therapy. Inadequate antimicrobial therapy
      decreases the possibility of positive outcome. Risk of resistance development
      should be monitored for every new antimicrobial agent. Cefepime is a new,
      parenteral, broad-spectrum, fourth-generation cephalosporin, an effective agent
      in the treatment of bacterial infections. Modification of the cefepime molecule
      gives rapid penetration into the bacterial cell, resulting in rapid bactericidal
      effect. Cefepime does not have the propensity to provoke septic shock due to
      bacterial endotoxins. It is also one of the three available antimicrobials
      (carbapenems, piperacylin/tazobactam, cefepime) with very good activity against
      many resistant nosocomial pathogens. Combination of cefepime with amikacin is
      thought as the most effective treatment of infections due to multidrugresistant
      Pseudomonas spp.

PMID- 14593684
TI  - [The present methods of diagnosing adenoidal hypertrophy in children].
AB  - The role of enlarged adenoids and tonsils in upper airway obstruction has become
      well-established earlier, thus, adenoidectomy with, or without, tonsillectomy is
      one of the most commonly performed surgical procedures in the paediatric
      population. Since the difficulty to objectively assess the adenoidal tissue and
      the nasopharyngeal airway in children, it is necessary to find out an accurate
      method of measuring these structures pre-operatively. In this work, the following
      methods are described: recording of obstructive symptoms, transoral posterior
      rhinoscopic examination, radiological evaluation, such as lateral radiography of
      the adenoid and nasopharyngeal magnetic resonance imaging, transnasal
      fiberoscopic examination, acoustic rhinometry and other.

PMID- 14593685
TI  - [Oktaw Pietruski (1820-1894) vice president of the Galician national seim -- his
      achievements in Polish laryngology].
AB  - The professional achievements of Oktaw Pietruski (1820-1894), a famous Polish
      lawyer and parliamentarian, v. president of the Galician National Seym are
      described. His struggle for a Polish character of Galicia, especially for
      introduction of an educational system and for introduction of Polish language in
      schools of different type in Galicia are presented. The achievements of Pietruski
      in origin of the Department of Laryngology of Medical Faculty of the Jagellonian
      University are described in more detail. The founder of this Department was
      Przemyslaw Pieniazek (185-1916), the first associate professor in Polish
      territories and later the first professor of rhinolaryngology, world famous
      physician.

PMID- 14593686
TI  - Introduction to the special section: death, dying, and bereavement.

PMID- 14593687
TI  - Relationships with death: the terminally ill talk about dying.
AB  - This article describes a qualitative study exploring the experiences of
      terminally ill patients and their families as they lived with the inevitability
      of death. Frustrated by the dominant discourse surrounding the culture of dying-
      namely that of Elisabeth Kubler-Ross's stage theory--I sought to revisit the
      experiences of the terminally ill by talking directly with them. Instead of
      focusing on how people reacted to the introduction of death into their lives,
      this research attended to how the dying began relating to life and death
      differently as a result of death's presence. Through an analysis of
      ethnographically collected data, the meanings participants constructed around
      their experiences were explored--culminating in the creation of seven
      "relationships" that participants shared with death.

PMID- 14593688
TI  - Healing loss, ambiguity, and trauma: a community-based intervention with families
      of union workers missing after the 9/11 attack in New York City.
AB  - A team of therapists from Minnesota and New York worked with labor union families
      of workers gone missing on September 11, 2001, after the attack on the World
      Trade Center, where they were employed. The clinical team shares what they did,
      what was learned, the questions raised, and preliminary evaluations about the
      multiple family meetings that were the major intervention. Because of the vast
      diversity, training of therapists and interventions for families aimed for
      cultural competence. The community-based approach, preferred by union families,
      plus family therapy using the lens of ambiguous loss are proposed as necessary
      additions to disaster work.

PMID- 14593689
TI  - The impact on the family therapist of a focus on death, dying, and bereavement.
AB  - Recognizing the growing numbers of family therapists who are choosing a focus on
      death, dying, and bereavement, this article addresses the nature of the
      commitment required--as well as the gifts and challenges presented by work in
      this area. Particular attention is given to therapists' vulnerability to
      compassion fatigue and/or vicarious traumatization, both of which are described
      and discussed. A variety of strategies for individuals and institutions, aimed at
      supporting professionals and preventing problems, are considered. It is concluded
      that as family therapists focus on self-care as well as client care, they have
      the potential to increase not only their effectiveness but also to enhance their
      own well-being. Implications for training and for research on this topic also are
      considered.

PMID- 14593690
TI  - The influence of caregiving stressors, social support, and caregiving appraisal
      on marital functioning among African American wife caregivers.
AB  - Using a stress and coping framework, we examined the influence of caregiving
      stressors, social support, and caregiving appraisal on the marital functioning of
      100 African American wife caregivers. Results of separate multivariate analyses
      revealed received church support, caregiving burden, and caregiving satisfaction
      significantly predicted wives' marital functioning, when caregivers' background
      characteristics (age and education), length of caregiving, whether first
      marriage, and urban versus rural location were controlled. Receiving church
      support was associated with increased marital functioning. Lower levels of
      caregiving burden were associated with increased marital functioning. Higher
      levels of caregiving satisfaction were associated with increased marital
      functioning. Findings illuminate wives' caregiving and marital experiences, and
      have implications for family therapy and future research.

PMID- 14593691
TI  - Multi-family psychoeducation groups in the treatment of children with mood
      disorders.
AB  - This study examined the impact of adjunctive multi-family psychoeducation groups
      (MFPG) on mood-disordered children aged 8 to 11 and their families. Participants
      were 35 children and 47 parents from families randomly assigned to either
      immediate MFPG plus treatment as usual (n = 18) or a 6-month wait-list condition
      plus treatment as usual (n = 17). At the 6 month follow up, immediate treatment
      families reported: Increased parental knowledge about childhood mood symptoms;
      increased positive family interactions as reported by the parent; increased
      perceptions of parental support as reported by children; and increased
      utilization of appropriate services by families. Expected impact on decreasing
      negative family interactions was not found. Results are largely consistent with
      hypothesized findings and support the need to further investigate the adjunctive
      role of psychoeducation in the treatment of childhood mood disorders.

PMID- 14593692
TI  - Conduct disorder and delinquency.
AB  - Overviews evidence-based family treatments for adolescent conduct problems. Three
      treatments succeed in meeting recommendations for treatment development set forth
      in recent evaluations by reviewers and federal entities. These treatments
      (Functional Family Therapy, Multisystemic Therapy, and Oregon Treatment Foster
      Care) have achieved their success by using the science base of known risk
      factors, providing an effective alternative to restrictive placements, and using
      scientific methods to evaluate effectiveness. Major features of these three
      treatments are presented, including clinical and quality assurance procedures,
      controlled outcome research support, cost analyses, and process research. Bases
      of treatment success and parallels among the three approaches are summarized, as
      is their transport and dissemination to practice settings. Finally, suggestions
      for future research and clinical implications are discussed.

PMID- 14593693
TI  - Childhood behavioral and emotional disorders.
AB  - We reviewed the literature on family treatment for childhood behavioral and
      emotional disorders and found an increase in the number of studies since 1995;
      however there was significant variation by disorder and therapy model. There is
      substantially more research on externalizing disorders (i.e., conduct disorder,
      attention deficit hyperactivity disorder, oppositional defiant disorder) then
      internalizing disorders, depression and anxiety disorders. The data support the
      conclusion that family-based interventions produce results comparable to
      individually oriented interventions, and in some cases family-based interventions
      are superior to individual treatments. To date, cognitive behavioral family
      therapy and parent management have been the two models studied, almost
      exclusively. Implications for family therapy and future research are considered.

PMID- 14593694
TI  - Meta-analysis of MFT interventions.
AB  - This article briefly reviews 20 meta-analyses of marital and family
      interventions. These meta-analyses support the efficacy of both MFT for
      distressed couples, and martial and family enrichment. Those effects are slightly
      reduced at follow-up, but still significant. Differences among kinds of marital
      and family interventions tend to be small. MFT produce clinically significant
      results in 40-50% of those treated, but the effects of MFT in clinically
      representative settings have not been much studied. The article also introduces
      the concept of meta-analytically supported treatments (MASTs), which are
      treatments that meet certain criteria for efficacy in meta-analysis, and which
      remedy certain problems in the empirically supported treatment (EST) literature.
      The article concludes with recommendations for doing better meta-analyses.

PMID- 14593695
TI  - Regulation of the eukaryotic cell cycle.
AB  - The sundry cellular processes required to successfully replicate and divide cells
      are driven by the sequential activation and inactivation of a family of cyclin
      dependent kinases. Activation is driven predominately by the periodic expression
      of the cyclin subunit and requires activating phosphorylation of the kinase
      subunit. Inactivation is controlled by inhibitory phosphorylation of the kinase
      subunit, by ubiquitin-mediated degradation of the cyclin subunit and by
      interaction of the complex with small inhibitory proteins. The mechanisms that
      coordinate cell cycle progression under favorable and adverse conditions are
      reviewed.

PMID- 14593696
TI  - Cell cycle deregulation: a common motif in cancer.
AB  - Uncontrolled proliferation is a hallmark of cancer cells. Molecular analysis of
      human tumors and animal models have provided a clear basis for the understanding
      of the cellular processes that govern cell cycle progression in normal and tumor
      cells. Many cell cycle regulators controlling the correct entry and progression
      through the cell cycle are altered in tumors. In fact, most, if not all, human
      cancers show a deregulated control of G1 progression, a period when cells decide
      whether to start proliferation or to stay quiescent. In addition, tumor cells
      have impaired cell cycle checkpoints, resulting in the accumulation of genetic
      aberrations. Manipulation of these control mechanisms provides new avenues for
      the design of advanced therapeutic strategies against tumor development.

PMID- 14593697
TI  - The cell cycle and cardiovascular diseases.
AB  - Cardiovascular diseases are the leading cause of morbidity and mortality in
      industrialized countries. Most cardiovascular diseases result from complications
      of atherosclerosis, which is a chronic and progression inflammatory condition
      characterized by excessive cellular proliferation of vascular smooth muscle
      cells, endothelial cells and inflammatory cells leading to occlusive vascular
      disease, myocardial infarction and stroke. Recent studies have revealed the
      important role of the cyclins, the cyclin-dependent kinases (CDKs), and the
      cyclin-dependent kinase inhibitors (CKIs) in vascular and cardiac tissue injury,
      inflammation and wound repair. Tissue remodeling in the cardiovascular system is
      a regulated balance between pro- and anti-proliferative molecules, and this
      balance becomes derailed in cardiovascular pathology. Understanding the circuitry
      of the cyclin-CDK-CKI interactions in normal physiology and disease pathology
      allows a better understanding of the molecular mechanisms of cardiovascular
      diseases and permits the rationale design of new classes of therapeutic agents
      for these diseases.

PMID- 14593698
TI  - The cell cycle and human neurodegenerative disease.
AB  - The mechanism by which neurons die in human neurodegenerative diseases remains an
      enigma till today. Terminally differentiated neurons of normal brain are
      incapable of cell division. However, accumulating evidence has suggested that
      aberrant activation of the cell cycle in certain degenerative diseases leads to
      their demise. In Alzheimer's disease, regulators spanning every phase of the cell
      cycle are upregulated in affected neurons, leading to successful DNA replication,
      but unsuccessful mitosis. The end point of this nonproductive cycle of division
      is death. Elucidating the details of this cell cycle-mediated degenerative
      cascade may lead to novel strategies for curbing the onset and progression of
      degenerative diseases.

PMID- 14593699
TI  - The cell cycle and tuberous sclerosis.
AB  - Tuberous sclerosis (TSC) is an autosomal dominant tumor suppressor gene syndrome
      occurring in about 1 in 6000 live births. Two genes have been shown to be
      responsible for this disease: TSC1 on chromosome 9q34, encoding hamartin, and
      TSC2 on chromosome 16p13.3, encoding tuberin. Although several different
      functions of these proteins have been described, the molecular mechanism for the
      development of TSC remains elusive. Mammalian and Drosophila TSC genes have been
      shown to be involved in cell cycle regulation. The Drosophila TSC genes have
      further been demonstrated to affect cell size control and to be related to the
      insulin signaling pathway. Very recent data provide evidence that mammalian TSC
      genes are also involved in cell size regulation.

PMID- 14593700
TI  - Airway smooth muscle cell hyperplasia: a therapeutic target in airway remodeling
      in asthma?
AB  - Severe asthma is characterized by airway remodeling due, in part, to increases in
      airway smooth muscle (ASM) mass. Regulation of ASM hyperplasia is considered an
      attractive therapeutic target for the potential treatment of airway remodeling in
      asthma. In order to develop anti-remodeling drugs, researchers have utilized cell
      culture techniques to elucidate the cellular and molecular mechanisms underlying
      ASM cell proliferation and to identify the critical cell cycle events that
      regulate ASM cell growth. Attractive lead compounds that have emerged from in
      vitro studies can now be examined in new animal models of airway remodeling, thus
      providing tools to design novel therapies to prevent or abrogate airway
      remodeling.

PMID- 14593701
TI  - Rheumatoid arthritis: targeting the proliferative fibroblasts.
AB  - Our flexible joints are synovial joints composed of bone, hyaline cartilage,
      synovial membrane, ligaments and tendons. Rheumatoid arthritis is a disease that
      affects multiple synovial joints and involves inflammation of the synovial
      membrane, often resulting in loss of function due to erosion of bone and
      cartilage. Inflammation is accompanied by an influx of immune-competent cells and
      by aberrant proliferation of resident fibroblast-like synoviocytes. Accretion of
      fibroblasts directly contributes to joint destruction, through enhanced
      production of matrix-degrading enzymes, and indirectly, through excessive release
      of cytokines that boost the immune system. Targeting the proliferative fibroblast
      could facilitate regeneration of synovial joints.

PMID- 14593702
TI  - Cell cycle control in glomerular disease.
AB  - Glomerular diseases are a leading caused of kidney failure. The three resident
      glomerular cell types respond differently to injury, which includes
      proliferation, hypertrophy, apoptosis and de-differentiation. Each leads to
      glomerular scarring, and a decline in renal function. Studies have shown that
      these events are critically controlled by cell cycle regulatory proteins,
      providing potential targets for the development of future therapeutics.

PMID- 14593703
TI  - The cell cycle of pathogenic fungi: target for drugs.
AB  - Life-threatening fungal infections are becoming more frequent and involve a
      greater variety of strains, many of which are drug-resistant. Both public
      research organisations and the pharmaceutical industry are committed to the
      development of new drugs to satisfy this increasing medical need. The approach
      described here exemplifies the efforts directed towards the discovery of drugs
      which are active against novel targets, exemplified by the cell-cycle regulator,
      Civ1.

PMID- 14593704
TI  - The cell cycle of parasitic protozoa: potential for chemotherapeutic
      exploitation.
AB  - There is an urgent need to develop new drugs against eukaryotic parasitic
      protozoa such as Plasmodium, Trypanosoma and Leishmania, which cause the diseases
      malaria, trypanosomiasis and the leishmaniases respectively. The biology of these
      organisms has many unusual facets that might be exploited for drug design, and
      the recent availability of parasite genome sequence data has facilitated the
      search for novel drug targets. Here we review current understanding of the cell
      cycle in these parasites and show that important structural and functional
      differences exist between parasite and mammalian cell cycle control machineries
      and signal transduction pathways, which might be utilised for rational drug
      design. Potential targets include protein kinases from the cyclin-dependent
      kinase, cAMP-dependent kinase and mitogen activated protein kinase families.

PMID- 14593705
TI  - The cell cycle, cyclin-dependent kinases, and viral infections: new horizons and
      unexpected connections.
AB  - The genomes of small DNA viruses such as papilloma and polyomaviruses code for
      few or no DNA replication proteins. Consequently, these viruses depend on
      cellular DNA replication proteins to replicate their genomes and replicate only
      when the infected cell progresses into S-phase, when these proteins are active.
      As a consequence of this strict dependence, the relationship between replication
      of the small DNA viruses and the cell cycle was obvious from the very early
      studies. The genomes of larger DNA viruses such as adeno- and herpes-viruses, in
      contrast, encode many of the proteins required for DNA replication. Some of the
      larger DNA viruses such as adenoviruses, however, also replicate only in S-phase
      because expression of viral DNA replication proteins is regulated by cellular
      factors that are activated in S-phase. Other large DNA viruses such as herpes
      simplex viruses (HSV) can replicate in arrested cells such as neurons, without
      inducing progression into S-phase. The relationships between cell cycle and
      replication of these last viruses are, thus, so subtle that their replication was
      long thought to be independent from cellular proteins whose activities are
      regulated in a cell cycle dependent manner. In contrast to this hypothesis,
      recent studies have shown that replication of HSV and other large DNA viruses
      requires cellular proteins whose activities are normally regulated in a cell
      cycle dependent manner, such as the cyclin-dependent kinases (cdks). Many
      excellent reviews on the interactions between cellular proteins involved in cell
      cycle regulation and smaller DNA viruses (parvo, papilloma, polyoma and
      adenoviruses) have been published (for example, see (1, 2)). Many reviews on cell
      cycle regulation also discuss the interactions between the cell cycle and the
      smaller DNA viruses (for example, see (3-5)). Herein, we will review these
      relationships only briefly, while focusing on the interactions between cell cycle
      proteins such as cdks and herpes-, retro, and hepadna-viruses. We will then
      succinctly discuss the surprising relationships between cdks and replication of
      some cytoplasmic RNA viruses. Lastly, we will present the possibility of applying
      the new information on the dependence of viral replication on cyclin-dependent
      kinases to the development of novel antiviral drugs.

PMID- 14593706
TI  - Small-molecule inhibitors of the cell cycle: an overview.
AB  - Potent and selective small-molecule mediated inhibition of the cell's replication
      machinery remains a principal aim in the development of novel therapeutics and
      biological probes. Recent efforts have identified small molecules capable of
      arresting the cell cycle via specific interaction with a variety of intracellular
      protein targets. Advances in combinatorial and diversity oriented synthetic
      methods, coupled with a continued effort to identify sources of bioactive natural
      products, promise to contribute to the growing library of small-molecule
      inhibitors of the cell cycle.

PMID- 14593707
TI  - Optimization of experimental antimitotic agents: classical and combinatorial
      methods.
AB  - Compounds that affect the progress of the cell cycle have served as useful tools
      for elucidating biological function and as leads for pharmacological agents.
      Historically, natural products derived from terrestrial and aquatic organisms
      have been the richest source of lead compounds and novel pharmacophores.
      Discovery and development of lead compounds from natural products has
      traditionally involved isolation of a natural product with the biochemical
      activity of interest, elucidation of its structure, development of chemical or
      biosynthetic methods for producing the compound and related compounds in larger
      quantities, and eventually examination of structure-activity relationships and
      pharmacological properties. Combinatorial chemistry has emerged as a powerful
      tool for the assembly of large collections of synthetic molecules; as such, it
      has been adopted in grand style by the pharmaceutical industry. Combinatorial
      chemistry can be applied in two modes: a diversity-generating mode, where known
      or novel scaffolds are elaborated into libraries and screened for new activities;
      or a focused mode, where attention is centered on a particular site in an effort
      to enhance a particular property (activity, selectivity, solubility, stability,
      bioavailability). In either mode, identification and development of compounds of
      interest is dependent on iterative rounds of compound optimization based on
      efficient and reliable biochemical, cellular, and phenotypic assays.

PMID- 14593708
TI  - The contemporary drug development process: advances and challenges in preclinical
      and clinical development.
AB  - We are in a new era of drug discovery, in which it is feasible to develop
      therapeutic agents targeted at a particular protein or biological activity in a
      living cell. This has been made possible by major advances in our understanding
      of cell and molecular biology, epitomized by the 2001 Nobel prize award for
      Physiology or Medicine to Lee Hartwell, Tim Hunt and Paul Nurse, who were
      recognised for their work on key regulators of the cell cycle. Technological
      advances have also played a decisive role, leading to the sequencing of the human
      genome and increased throughput at many stages of the drug discovery and
      development process. For example, developments in high throughput screening,
      structural biology and microarray technology are increasing the speed of drug
      discovery. In this chapter we focus on the long, and often difficult, pathway
      which leads from identification of a hit in a screen to regulatory approval of a
      drug for disease treatment. The emphasis in this chapter is on the development of
      anticancer drugs, as this is our own area of expertise and also because cancer is
      a disease in which the cell cycle is already a major target for therapeutic
      intervention. However, many of the concepts, approaches and issues are generally
      common to other therapeutic areas.

PMID- 14593709
TI  - Yeast genomics and proteomics in drug discovery and target validation.
AB  - Small, cell permeable, and target-specific chemical ligands are highly valuable,
      not only as therapeutics but also as research tools. The synthesis,
      identification and characterization of these compounds is often a difficult task.
      The straightforward genetics of the budding yeast Saccharomyces cerevisiae, and
      the high degree of conservation of basic cellular processes between yeast and
      higher organisms makes yeast an excellent tool for drug development studies,
      particularly in regards to anticancer and anti-fungal drug discovery. Recent
      advances in yeast functional genomics and proteomics studies are changing the
      field of yeast research. Many of these new technologies are readily applicable to
      drug target identification and other aspects of drug discovery. This review will
      focus on current genetic, genomic, and proteomic methodologies in S. cerevisiae
      that have the potential to be useful in drug discovery and target validation.

PMID- 14593710
TI  - Proteomic approaches for the identification of cell cycle-related drug targets.
AB  - Drugs affecting the cell cycle provide insights into mechanisms underlying cancer
      and suggest strategies for ablating uncontrolled growth. Essential to an
      understanding of the activity of such compounds is the identification of the set
      of proteins affected, either directly or indirectly, by the drug. The combination
      of novel technologies for stable isotope protein tagging, chromatographic
      separation, tandem mass spectrometry, and data processing is an extremely
      powerful means for providing such identifications and, in addition, for
      establishing a proteome-wide profile of all proteins whose abundance levels or
      phosphorylation state are affected by the drug.

PMID- 14593711
TI  - Mining the NCI screening database: explorations of agents involved in cell cycle
      regulation.
AB  - We propose an integrated application of technologies, computation and statistical
      methods to design experiments for examination of cellular pathways that are
      necessary for cell survival and that are candidates for cancer therapy. Our
      design combines information derived from two very different data sets: tumor
      screening data from over 36,000 synthetic compounds screened against over 60
      tumor cell lines, and replicate microarray gene expression measurements using one
      cell line and one compound. Data filtering, based on restricted cellular
      cytotoxicity profiles from chemically similar sets of compounds, has been used to
      select a class of benzothiazoles for subsequent microarray gene expression
      measurements in the most chemosensitive tumor cell line. The results confirmed
      observations that P450 metabolizing isoforms, CYP1A1 and CYP1B1, are
      overexpressed in MCF-7 tumor cells following treatment with benzothiazole. These
      results are consistent with the proposed inactivity of the CYP1A1-mediated
      metabolism of benzothiazole and the antitumor activity of the metabolically
      resistant halogenated forms.

PMID- 14593712
TI  - The role of cytosolic phospholipase A2 in cell cycle progression.
AB  - Cytosolic phospholipase A2 (cPLA2) cleaves fatty acids from the sn-2 position of
      phospholipids resulting in the release of arachidonic acid. cPLA2 is activated
      upon phosphorylation, followed by a Ca(2+)-dependent translocation to cellular
      membranes. The activity of cPLA2 has been demonstrated to fluctuate during the M,
      G1 and S-phases of the cell cycle, and it has been shown recently that inhibition
      of the relatively high activity during the initial phases of the cell cycle
      results in a drastic reduction in S-phase entry. These findings demonstrate that
      in addition to a role in the inflammatory response, cPLA2 plays also an important
      regulatory role in cell cycle progression.

PMID- 14593714
TI  - Rho family-associated kinases PAK1 and rock.
AB  - Rho family GTPases (Rho, Rac and CDC42) share around 30% sequence identity with
      RAS family GTPases, and are essential for RAS-induced malignant transformation,
      i.e., aberrant serum/anchorage-independent growth and actin cytoskeleton-linked
      morphological changes. Oncogenic RAS mutants such as v-Ha-RAS trigger cell cycle
      entry (G0-G1 transition) mainly by up-regulating cyclin D1, an activator of
      cyclin-dependent kinases (CDK), and down-regulating p27, a CDK inhibitor.
      Although both Rac and CDC42 are clearly activated by RAS, there is so far no
      evidence that RAS activates Rho. In this chapter, we will discuss the role of
      these Rho family GTPases and their effectors, in particular the Ser/Thr kinases
      PAK1 and Rock, in RAS-induced serum/anchorage-independent cell cycling, and
      discuss several potential therapeutics, peptides or chemical compounds, that
      could block this oncogenic cell cycle signalling pathway.

PMID- 14593713
TI  - Phospholipase D and choline kinase: their role in cancer development and their
      potential as drug targets.
AB  - Malignant cells result from the accumulation of genetic alterations that impinge
      into the components of signal transduction pathways controlling cell growth,
      differentiation and apoptosis. One of the critical pathways is related to the
      regulation of the phospholipid homeostasis. The identification of the molecular
      components involved in normal cell growth regulation altered upon transformation
      is required for the development of chemotherapeutic interventions against
      transformed cells. Discovery of new chemotherapeutic agents is one of the most
      promising ways to improve our success against cancer, and rational drug design is
      a key factor to achieve this goal. Evidence supporting choline kinase and
      phospholipase D as such novel targets is provided.

PMID- 14593715
TI  - The development of protein farnesyltransferase inhibitors as signaling-based
      anticancer agents.
AB  - The presence of mutated Ras in more that 30% of human cancers has spurred
      interest in the identification of molecules that can block its uncontrolled
      signaling function. A particular focus in recent years has been a key
      posttranslational modification of Ras that places a farnesyl group on a cysteine
      residue near the C-terminus of the protein. In this chapter we describe recent
      progress in the design of inhibitors for the enzyme that catalyzes this step,
      protein farnesyltransferase, and show their potential for blocking oncogenic cell
      growth.

PMID- 14593716
TI  - Pharmacological inhibitors of the ERK signaling pathway: application as
      anticancer drugs.
AB  - The ERK signaling pathway, also known as the p42/p44 MAP kinase pathway, is a
      major determinant in the control of cell growth, cell differentiation and cell
      survival. This pathway, which operates downstream of Ras, is often up-regulated
      in human tumors and as such represents an attractive target for anticancer
      therapy. In this chapter we review the rationale for targeting the components of
      the ERK pathway, either alone or in association with cytotoxic anticancer agents.
      We present the most advanced inhibitors of this pathway and discuss their
      specificity and mechanism of action.

PMID- 14593717
TI  - Inhibitors of the CDC25 phosphatases.
AB  - As essential cell cycle regulators, the CDC25 phosphatases are currently
      considered as potential targets for the development of novel therapeutic
      approaches. Here, we review the function and regulation of CDC25 phosphatases,
      their involvement in cancer and Alzheimer's disease, and the properties of
      several recently identified inhibitors.

PMID- 14593718
TI  - Cyclin-dependent kinase inhibitors.
AB  - Cyclin-dependent kinases are involved in diverse cellular processes that include
      cell cycle control, apoptosis, neuronal physiology, differentiation, and
      transcription. Intensive screening and drug design based on CDK/inhibitor co
      crystal structures and on SAR studies have led to the identification and
      characterization of a large variety of chemical inhibitors of CDKs. Although they
      all act by competing with ATP for binding at the catalytic site of the kinase,
      their kinase selectivity varies greatly and remains to be studied in most cases.
      The requirement for CDKs in many physiological processes justifies their
      evaluation as potential therapeutic targets against a much larger scope of
      diseases than initially anticipated.

PMID- 14593719
TI  - p27kip1 contributions to cancer.
AB  - Deregulation of the tumor suppressor p27kip1 (p27) has been implicated in a
      variety of human cancers, suggesting it might be a viable therapeutic target.
      Developing p27-specific intervention strategies requires understanding its role
      and regulation in normal and pathologic states. Although p27 has been extensively
      characterized as an inhibitor of cyclin-dependent kinases, disruption of this
      function is inadequate to explain its role in tumorigenesis. A more comprehensive
      understanding of p27 biology would facilitate development of therapeutic
      responses to p27 disruption in human cancers.

PMID- 14593720
TI  - Aryl hydrocarbon receptor-mediated cell cycle control.
AB  - The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor
      responsive to both natural and man-made environmental compounds. AhR-mediated
      changes in gene expression frequently affect cell growth, and recent evidence
      reveals a direct role for the AhR in cell cycle control. This review examines the
      functional interaction between the AhR and the retinoblastoma tumor suppressor
      protein (pRb), and its impact on the G1 phase of the cell cycle. The discussion
      emphasizes gaps in our mechanistic understanding, and reveals the AhR signaling
      pathway as a novel drug target to control cell proliferation.

PMID- 14593721
TI  - Protein deacetylases: enzymes with functional diversity as novel therapeutic
      targets.
AB  - It is becoming increasingly clear that reversible acetylation of proteins is a
      signal directly controlling the activity of key cellular regulators. The enzymes
      controlling protein acetylation were identified as histone acetyltransferases
      (HATs) and histone deacetylases (HDACs). Following the discovery of HATs and
      HDACs, a number of non-histone proteins have been identified as substrates for
      these enzymes. HDACs play important roles in transcriptional regulation and
      pathogenesis of cancer through removing acetyl groups from histones and other
      transcriptional regulators. HDAC inhibitors case cell cycle arrest,
      differentiation and/or apoptosis of many tumors, suggesting their usefulness for
      chemotherapy and differentiation therapy. Since recent studies have revealed that
      HDACs are structurally and functionally diverse, it should be possible to develop
      inhibitors specific to individual HDACs as more promising agents for cancer
      therapy.

PMID- 14593722
TI  - HMGA proteins as therapeutic drug targets.
AB  - Members of the HMGA (formerly known as HMGI/Y) family of non-histone chromatin
      proteins function as important accessory factors in many normal nuclear
      processes, including the modulation of chromosome structure, chromatin and
      nucleosome remodeling and the control of gene transcription. The HMGA proteins
      are also frequently associated with various malignancies. The aberrant expression
      or over-expression of these proteins is, for example, associated with many
      different types of tumors. The HMGA proteins also appear to be the host-supplied
      cofactors necessary for efficient integration of retroviruses, such as HIV, into
      the genome. The HMGA proteins appear, therefore, to be promising targets for
      therapeutic drugs aimed at alleviating these and other pathological conditions.

PMID- 14593723
TI  - The role of the replication licensing system in cell proliferation and cancer.
AB  - The precise duplication of chromosomal DNA during each cell cycle is essential
      for the maintenance of genetic stability. Failure to correctly regulate
      chromosomal DNA replication could lead to losses or duplication of chromosome
      segments. The precise duplication of chromosomes is normally achieved by correct
      regulation of the replication licensing system. Here we review our current
      knowledge of the licensing system and how this might be defective in cancer
      cells. We also review how detection of licensing components can be used for the
      diagnosis and prognosis of cancer. Finally we discuss the potential of the
      replication licensing system as a novel anti-cancer target.

PMID- 14593724
TI  - From DNA damage to G2 arrest: the many roles of topoisomerase II.
AB  - DNA topoisomerase II inhibitors are among the most widely used anticancer agents.
      These drugs are potent inducers of DNA strand breaks and G2 arrest. However,
      topoisomerase II is not only a target for anti-cancer drugs but also part of the
      cellular response to different types of DNA damage. Topoisomerase II forms
      molecular complexes with important cell cycle regulators including the p53
      oncogene suppressor, the BRCT-containing protein TopBP1, 14-3-3 epsilon and Cdc2
      kinase. The association between topoisomerase II and Cdc2 kinase likely
      represents the earliest step in mitotic chromatin condensation. Therefore,
      regulation of the topoisomerase II/Cdc2 interaction could represent a novel
      mechanism to delay mitotic onset.

PMID- 14593726
TI  - Tubulin and microtubules as targets for anticancer drugs.
AB  - Microtubules are intracellular organelles formed from the protein tubulin. These
      organelles have a number of essential cellular functions including chromosome
      segregation, the maintenance of cell shape, transport, motility, and organelle
      distribution. Drugs that affect the tubulin-microtubule equilibrium (taxol, vinca
      alkaloids) are effective anticancer drugs. This review describes the molecular
      target, methods used in screening, the structures of compounds known to interact
      with tubulin, and the clinical use of these agents. In addition the ability of
      these agents to destroy tumour vasculature is described. This represents an
      exciting new molecular target in the design of anticancer drugs.

PMID- 14593725
TI  - Regulators of nucleolar functions.
AB  - The nucleolus is the ribosome factory and also a multifunctional domain that
      plays an important role in nuclear organization and function. Interestingly,
      ribosome biogenesis appears directly related to cell growth and proliferation.
      The nucleolus corresponds to a very dynamic nuclear domain resulting from an
      equilibrium between the level of ribosomal RNA synthesis and the efficiency of
      ribosomal RNA processing. Ribosome biogenesis is regulated throughout interphase
      and stops during mitosis. The mitotic silencing of transcription, the
      distribution of the processing machinery, as well as the link between
      transcription and processing were found to be dependent on cyclin-dependent
      kinase(s).

PMID- 14593727
TI  - Polo-like kinases and the microtubule organization center: targets for cancer
      therapies.
AB  - Studies from eukaryotic model systems, ranging from yeast to human, indicate that
      Polo and Polo-like kinases (Plks) are essential for the activity of the
      microtubule organization center. Polo/Plks localize to centrosomes or spindle
      pole bodies and undergo dramatic subcellular relocation during the cell cycle.
      Deregulated activities of Plks often result in abnormalities in centrosome
      duplication, maturation, and/or microtubule dynamics. Genetic and biochemical
      approaches have identified several candidate genes that either lie in the same
      pathway as POLO/PLKs or whose products are direct targets of Polo/Plks during the
      centrosome cycle. Recent studies have demonstrated that mammalian Plks also
      regulate the function of the Golgi complex, a cellular organelle closely
      associated with the centrosome and also having microtubule organization activity.
      Furthermore, deregulated expression of human PLK1 and PLK3 is strongly correlated
      with the development of many types of malignancies, and ectopic expression of
      kinase-active Plk3 or Plk1 dominant negative protein leads to rapid cell death.
      Given that several effective anti-tumor drugs directly interfere with microtubule
      dynamics, mammalian Plks are excellent targets for the development of anticancer
      drugs.

PMID- 14593728
TI  - Cyclin B1 and CDK1: nuclear localization and upstream regulators.
AB  - Formation of an active nuclear cyclin B1-CDK1 complex is a highly intricate
      procedure requiring many different levels of regulation. Each of these regulatory
      steps represents a potential target for controlling cell proliferation.
      Accumulation of threshold levels of cyclin B1 protein at the G2/M transition
      requires the cooperation of various promoter elements, possibly the activation of
      several transcription factors, enhanced cyclin B1 mRNA stability and, in some
      cases, translational activation of dormant mRNA. Binding of cyclin B1 to its
      inactive partner, CDK1, initiates conformational changes allowing CDK1 to alter
      its phosphorylation status and to become an active kinase. Lastly, the active
      cyclin B1-CDK1 complex must translocate to the nucleus to begin phosphorylating
      nuclear substrates. These phosphorylation events are necessary for mitotic onset.
      While cyclin B1 is capable of shuttling from the nucleus to the cytoplasm
      throughout interphase, mitotic onset requires phosphorylation of cyclin B1 within
      the CRS region, thereby enhancing import and inhibiting export of the cyclin B1
      CDK1 complex. Elucidating the role of mediators controlling cyclin B1-CDK1
      translocation at the onset of mitosis is essential in developing drug targets for
      cell cycle control.

PMID- 14593729
TI  - Dynamics of the mitotic spindle--potential therapeutic targets.
AB  - Inhibition of mitosis is a useful strategy for treating diseases involving
      excessive cell proliferation. Antimitotic drugs currently in clinical use perturb
      microtubule dynamics and thereby disrupt the function of the mitotic spindle.
      Protein regulators of microtubule dynamics and microtubule motors are also
      essential for mitotic spindle function. In this chapter, we evaluate the
      potential of these proteins as candidate targets for antimitotic drugs. We review
      in depth a number of proteins of particular interest, highlighting their known
      functions in mitosis and the effects of their inhibition on cell cycle
      progression.

PMID- 14593730
TI  - Condensin and biological role of chromosome condensation.
AB  - Mitotic chromosome condensation is an essential cellular function ensuring proper
      compaction and segregation of sister chromatids during cell division. Condensin,
      a five-subunit complex, conserved among eukaryotes, is the key molecular machine
      of chromosome condensation. Recent advances in the structural biology and
      functional analysis of condensin demonstrate the unique nature and indispensable
      biological role of this complex. Condensin functions span chromosome dynamics
      during mitotic cell division, cell-cycle feedback control mechanisms, as well as
      formation and maintenance of interphase chromosome structure. Being at the
      intersection of several cell-cycle regulatory networks condensin is a promising
      therapeutic target for control over cell proliferation.

PMID- 14593731
TI  - Phosphorylation of histone and histone-like proteins by aurora kinases during
      mitosis.
AB  - Successful cell division requires that daughter cells inherit not only a complete
      set of chromosomes, but also only one centrosome, and similar amounts of
      organelles and cytoplasmic components. The different mitotic processes are driven
      by cell cycle-regulated protein kinases and phosphatases and their fidelity is
      closely monitored by a number of checkpoint mechanisms. Histone H3 is
      phosphorylated during mitosis, but the kinases involved were not known until
      recently. Recent work has revealed that Aurora kinases are required for mitotic
      phosphorylation of histone H3 and of its centromeric variant CENP-A. This finding
      has stimulated functional studies of the role(s) of Aurora kinases and H3
      phosphorylation during mitosis, which are reviewed in this chapter.

PMID- 14593732
TI  - Drug discovery and the p53 family.
AB  - The tumour suppressor activity of p53 plays a major role in limiting abnormal
      proliferation, and inactivation of the p53 response is becoming increasingly
      accepted as a hallmark of cancer. In contrast, both p63 and p73, which are close
      relatives of p53, are rarely mutated in tumour cells. At a theoretical level,
      therapeutic approaches that reinstate p53 activity, or augment p63 and p73,
      provide plausible and potentially efficacious routes towards new cancer
      treatments. Equally important is the clinical need to increase the efficacy of
      conventional anti-cancer drugs. Incapacitating the p53 response to limit the side
      effects in healthy cells may be one approach towards increasing the therapeutic
      window of many current anti-cancer drugs. Nevertheless, while cancer drug
      discovery focussed on p53 is an exciting and realistic possibility, translating
      this concept into a clinical setting is likely to be challenging.

PMID- 14593733
TI  - Centrosome abnormalities and genomic instability induced by human papillomavirus
      oncoproteins.
AB  - Cervical cancer is tightly associated with infection by high-risk human
      papillomaviruses (HPVs). Many high-risk HPV-positive lesions are genomically
      unstable and show chromosomal gains and losses already at early stages of
      carcinogenic progression. These genomic aberrations are caused by the HPV-encoded
      oncoproteins E6 and E7, which subvert mitotic fidelity of the infected host cell.
      Whereas E7 drives genomic instability by inducing abnormal centrosome numbers, E6
      cooperates with E7 presumably by relaxing critical checkpoint control mechanisms.
      The ability of E7 to induce centrosome duplication errors (CDEs) may be linked to
      the re-programming of the host cell cycle machinery, including dysregulation of
      cyclin/cyclin-dependent kinase (cdk) 2 activity. Given the role of cdk2 as a
      regulatory node not only for cell cycle progression but also for centrosome
      duplication, inhibition of cdk2 may not only retard cellular proliferation but
      also decrease CDEs and centrosome-related mitotic defects. Compared to some
      conventional cytotoxic agents, which exclusively target DNA replication,
      modulation of cdk2 activity may hold the promise of diminishing the development
      of genomically unstable, aneuploid tumor cells that are frequently the source of
      chemotherapy resistance in malignant tumors.

PMID- 14593734
TI  - The role of ATM and ATR in DNA damage-induced cell cycle control.
AB  - Ataxia-Telangiectasia mutated (ATM) and ATM- and Rad3-related (ATR) are members
      of the phosphatidyl inositol 3-kinase-like family of serine/threonine protein
      kinases (PIKKs), and play important roles in the cellular response to DNA damage.
      Activation of ATM by ionizing radiation results in the activation of signal
      transduction pathways that induce cell cycle arrest at G1/S, S and G2/M. ATR is
      required for cell cycle arrest in response to DNA-damaging agents such as
      ultraviolet radiation that cause bulky lesions. This review focuses on the role
      of ATM and ATR in various DNA damage response pathways, and discusses the
      potential for targeting these pathways for the development of novel therapeutics.

PMID- 14593735
TI  - Drug discovery targeting Chk1 and Chk2 kinases.
AB  - The DNA damage response includes not only checkpoint and apoptosis, but also
      direct activation of DNA repair networks. Downstream in the DNA damage response
      pathway are Chk1, an essential checkpoint kinase, and Chk2, which plays a
      critical role in p53-dependent apoptosis. Chk1 inhibition is expected to lead to
      chemosensitization of tumors, while Chk2 inhibition could protect normal
      sensitive tissues from some chemotherapeutic agents. Drugs targeting Chk1 and
      Chk2 have the potential to significantly improve the therapeutic window of DNA
      damaging agents available in the clinic.

PMID- 14593736
TI  - Inhibitors of the G2 DNA damage checkpoint and their potential for cancer
      therapy.
AB  - Cells normally respond to DNA damage by activating checkpoints that delay the
      transition from G1 to S and from G2 to M while DNA is repaired. The checkpoints
      thus protect cells by blocking replication of damaged DNA and segregation of
      damaged chromosomes. Most cancer cells have an inoperative G1 checkpoint due to
      p53 inactivation, and a functioning but impaired G2 checkpoint. Inhibitors of the
      G2 checkpoint can selectively sensitize cells with inactive p53 to killing by DNA
      damaging drugs or ionizing radiation and might be useful in cancer therapy. Cell
      based and target-directed screens for checkpoint inhibitors have been developed
      and several checkpoint inhibitors have been identified. This review describes
      their chemical structures, biochemical targets and cellular effects and discusses
      their therapeutic potential.

PMID- 14593737
TI  - The mitotic checkpoint: a signaling pathway that allows a single unattached
      kinetochore to inhibit mitotic exit.
AB  - The mitotic checkpoint is a failsafe mechanism for the cell to ensure accurate
      chromosome segregation during mitosis. Mutations in genes encoding essential
      checkpoint proteins lead to chromosome instability and promote carcinogenesis.
      The BUB and MAD genes are essential components of the mitotic checkpoint pathway.
      BUB and MAD inhibit the ubiquitin ligase activity of the Anaphase Promoting
      Complex/Cyclosome (APC/C) during mitosis to ensure cells with unaligned
      chromosomes do not prematurely enter anaphase. Two models explain how the APC/C
      is inhibited by the checkpoint. The Sequestration Model postulates that Mad2 and
      BubR1 bind and sequester Cdc20, an APC/C activator, away from APC/C so substrates
      whose destruction drives mitotic exit are no longer ubiquitinated. In this model,
      the unattached kinetochore is postulated to catalytically convert Mad2 to a form
      that binds Cdc20. In the Direct Inhibition Model, the Mitotic Checkpoint Complex
      (MCC) consisting of BubR1, Bub3, Mad2 and Cdc20 binds and inhibits the APC/C
      independently of the kinetochore. However, the "wait anaphase" signal generated
      by unattached kinetochores sensitizes the APC/C to prolonged inhibition by the
      MCC. A single unattached kinetochore is proposed to amplify the "wait anaphase"
      signal through a kinase cascade involving checkpoint kinases such as hBubR1,
      hBub1 and Mps1.

PMID- 14593738
TI  - Interruption of tumor cell cycle progression through proteasome inhibition:
      implications for cancer therapy.
AB  - The ubiquitin/proteasome-dependent protein degradation pathway plays an essential
      role in both up-regulation of cell proliferation and down-regulation of cell
      death in human cancer cells. The idea that proteasome function is required for
      tumor cell survival has prompted the design, synthesis and evaluation of various
      pharmacological proteasome inhibitors. Both in vitro and in vivo experimental and
      clinical results have demonstrated the potential use of proteasome inhibitors as
      novel anticancer drugs.

PMID- 14593740
TI  - The role of cyclin-dependent kinases in apoptosis.
AB  - Cell division and apoptosis are key aspects of cancer biology. The combination of
      increased cell proliferation and reduced cell death lies very close to the reason
      why cancer is a deadly disease. The importance of apoptosis and cell division in
      tumor biology has made them targets of new anti-cancer therapies. Although the
      cell division cycle and apoptosis might appear to be quite different from a
      physiological perspective and thus provide independent targets for therapy,
      recent evidence suggests that they are intertwined, and that an enzyme in one
      system might also have an important role in the other system. Protein kinase
      complexes known as cyclin-dependent kinases (Cdks) are the first example of such
      enzymes. In this review, we focus on the role of the subunits of different Cdks
      in both apoptosis and the cell cycle.

PMID- 14593739
TI  - Survivin in apoptosis control and cell cycle regulation in cancer.
AB  - Evasion of apoptosis, and the ability to proliferate uncontrollably are two of
      the molecular traits found perhaps in all human cancers (1). Positioned at the
      interface between the regulation of apoptosis and the control of cell
      proliferation, survivin is a recently described molecule that is expressed in
      most human cancers but not in normal tissues. Encouraging new studies demonstrate
      that it may be possible to exploit the survivin pathway for cancer diagnosis and
      therapy.

PMID- 14593741
TI  - Drugs affecting the cell cycle via actions on the polyamine metabolic pathway.
AB  - Polyamines (putrescine, spermidine, and spermine) are ubiquitous cellular
      components that have multiple functions, including actions affecting the cell
      cycle. Polyamine biosynthesis and content is altered during the course of cell
      cycling via changes in two key biosynthetic enzymes, ornithine decarboxylase and
      S-adenosyl-methionine decarboxylase. Decreases in polyamine content and/or
      alterations in the relative amounts of polyamines can be achieved by treatment
      with inhibitors of these enzymes or by application of polyamine analogues, which
      subvert mechanisms for polyamine homeostasis and may interfere directly with
      polyamine-dependent processes. Such changes cause G1 and G2-M cell cycle blocks
      that can be brought about via induction of p21WAF1/CIP1.

PMID- 14593742
TI  - Cap-dependent translation and control of the cell cycle.
AB  - The control of gene expression at the translational level has emerged in the past
      decade as an important aspect of cell growth, proliferation and malignant
      transformation. Translation is primarily regulated at the initiation step, and
      mitogen-dependent signaling pathways converge to modulate the activity of
      translation initiation factors. In most tumors tested, at least one translation
      initiation factor is overexpressed and overexpression of translation initiation
      factors often provokes transformation. Malignant transformation could be caused
      by the increased translation of a subset of mRNAs encoding important proteins
      which are required for cell growth and proliferation. These mRNAs usually possess
      regulatory sequences that render their translation more sensitive to changes in
      the activity of translation initiation factors. In this chapter, we describe
      recent advances illustrating the importance of translation in cell cycle
      progression and cell transformation. Control of translation initiation may
      represent an excellent target for antitumor drugs.

PMID- 14593743
TI  - The peptidyl-prolyl isomerase Pin1.
AB  - The phospho-Ser/Thr-Pro specific prolyl-isomerase Pin1 has been implicated in
      multiple aspects of cell cycle regulation. It has been suggested that Pin1
      function is required for both normal mitotic progression and reentry into the
      cell cycle from quiescence. In support of this hypothesis, numerous key
      regulators of G1 and mitosis have been identified as Pin1 interacting proteins.
      However, the cellular consequence of Pin1 binding to these proteins has rarely
      been rigorously characterized. In this review we focus on the role of Pin1 and
      its binding proteins in cell cycle regulation and the potential value of Pin1 as
      a therapeutic target.

PMID- 14593744
TI  - The interaction of glycogen synthase kinase-3 (GSK-3) with the cell cycle.
AB  - GSK-3 is a multifunctional protein kinase known to play a pivotal role in the
      regulation of metabolism, the cytoskeleton and gene expression. It also interacts
      with the cell cycle in a number of ways. GSK-3 forms part of both Wnt and Hh
      signalling pathways and hence controls expression of a number of cell cycle
      regulatory genes. Prominent among these is cyclin D1. GSK-3 also phosphorylates
      cyclin D1 to promote its nuclear export and subsequent degradation. In this
      chapter we examine how GSK-3 mediates these effects and consider how therapeutic
      strategies may be developed to specifically target these pathways.

PMID- 14593745
TI  - Roles and regulation of serine/threonine-specific protein phosphatases in the
      cell cycle.
AB  - As cell cycle research enters its fourth decade, multiple protein kinases are
      firmly established as key regulators of the cell cycle, and some of them have
      emerged as promising drug targets. This review will discuss the serine/threonine
      specific protein phosphatases that oppose the actions of protein kinases.
      Typically, a phosphatase may stimulate one cell cycle transition, and inhibit
      another; alternatively, two different phosphatase holoenzymes may have opposing
      effects on the same cell cycle transition. Thus, both activation and inhibition
      of these enzymes could result in cell cycle arrest and/or apoptosis. Specific
      findings, the challenges and approaches to exploit this potential will be
      discussed.

PMID- 14593746
TI  - The actin cytoskeleton as a therapeutic target: state of the art and future
      directions.
AB  - Dynamic processes such as cell migration and division depend on the actin
      cytoskeleton, a dense meshwork of protein polymers capable of undergoing rapid
      cycles of assembly and disassembly, under the control of a large number of actin
      associated proteins. In cancer cells, structural and functional perturbations of
      the actin cytoskeleton correlate with higher proliferation rates and uncontrolled
      movement. Therefore, small molecules that act on the actin cytoskeleton of tumour
      cells and thus inhibit cell division and movement, may be of high therapeutic
      value. The dynamic properties of the actin cytoskeleton and the mechanism of
      action of actin-targeting drugs will be described.

PMID- 14593747
TI  - Selective protection of normal proliferating cells against the toxic effects of
      chemotherapeutic agents.
AB  - A major problem of cancer therapy is to not kill the normal cells essential for
      life while killing the great majority of cancer cells. Subtle differences that
      arise during progression of cancer can provide novel therapies, such as targeting
      normal cells for protection against chemotoxicity. The increasing understanding
      gained by applying cellular and molecular biological techniques including
      expression genetics to detect molecular differences is revealing potential
      targets, related to cell proliferation, apoptosis, and differentiation. The
      quantitative differences of gene or enzyme expression between normal and tumor
      cells have provided the basis for drug discovery that can either reversibly
      target the normal cells or differentially target the tumor cells. Such
      differences also emphasize the need for the application of multiple drugs, with
      different modes of action.

PMID- 14593748
TI  - Cytometry of cell cycle regulatory proteins.
AB  - Immunocytochemical detection of cyclins, inhibitors of cyclin-dependent kinases
      and other cell cycle regulatory proteins, combined with analysis of cell cycle
      position (DNA content) by multiparameter cytometry offers unique analytical
      possibilities. This review focuses on applications of the methodology that yield
      information on the abundance, modification or interactions of these proteins in
      relation to cell cycle progression that cannot be obtained by other methods.
      Particular attention is given to the use of multiparameter cytometry in analysis
      of the mechanism by which antitumor drugs affect cell cycle progression and
      induce cell cycle phase-specific apoptosis.

PMID- 14593749
TI  - [The prospects for clinical use of neurotrophins in therapy].
AB  - In view of neuroprotective effects of neurotrophins and neurotrophic factors on
      the damaged nervous tissue clinical attempts have been made to use these proteins
      in the treatment of neurodegenerative diseases. However, the attempts were
      unsuccessful. We discuss the main causes of this failure and outline a new
      clinical prospect due to the growing understanding of the mechanisms underlying
      neurotrophin activity in the nervous system. A special emphasis has been laid on
      advances in the research aimed at optimization of pharmacodynamics of
      neurotrophins, and at development of new delivery systems that would not only
      supplement the nervous system with required neurotrophins locally, but also
      regulate their quantity and time span of their delivery. An alternative method of
      physical exercise allowing to upregulate neurotrophins and their receptors is
      also discussed.

PMID- 14593751
TI  - [The "Functional -QEMG" method -- a substantial progress in electromyography
      (EMG)].
AB  - In contradistinction to the traditional quantitative EMG, our new "Functional
      QEMG" method provides new information about structural and functional changes in
      the whole population of active motor units (MUs) in various neuromuscular
      disorders. Individual motor unit action potentials (MUAPs) and the interference
      pattern (IP) recordings are analyzed not as complementary measurements but as one
      integral test. Such a complex of EMG signals is submitted to a non-linear dynamic
      analysis determining interrelationships between an active MU size and its
      functional properties. Structural changes in MU size represent the primary
      destructive process, while the resulting changes in MU functional properties due
      to a compensatory mechanism (a secondary restorative process) provide new and
      very useful diagnostic information. All EMG data are processed online and
      automatically classified by a special computer-assisted diagnostic program as
      either a normal or pathological (myogenic or neurogenic) EMG recording. At the
      same time severity of muscle damage is assessed. This article illustrates how
      both the efficacy and limitations of compensatory mechanisms are related to
      structural damage in various neuromuscular disorders. The "Functional-QEMG"
      method application in clinical practice for over ten years has evidenced that
      this new approach is a turning point in improving the EMG diagnosis. This
      automatic method provides online reliable answers to most of the questions facing
      an electromyographer in daily routine investigations.

PMID- 14593750
TI  - [Determinants of tiagabine (TGB) efficacy and safety. A Polish multicenter study
      of 1307 patients with focal epilepsy].
AB  - Tiagabine (TGB) is a novel anti-epileptic drug providing new therapeutic
      possibilities to patients with focal seizures resistant to treatment. Since there
      is no clear algorithm for the best add-on therapy, the aim of our work was to
      establish factors that statistically significantly affect tiagabine efficacy and
      toxicity in patients with focal seizures. Data in the study were obtained from
      over 200 neurologists all over Poland. A group of 1307 patients aged from 3.5 to
      80 years with drug-resistant focal epilepsy participated in the study. They were
      under observation for 16 weeks when receiving TGB as an add-on therapy. Prior to
      TGB treatment they had at least 1 seizure per month (mean 7.42 +/- 9.86) during
      the past 3 months. On the study completion 40.47% of the patients were seizure
      free for at least a month. Two factors turned out to be significant for TGB
      efficacy: the number of drugs used since the onset of epilepsy (p = 0.005) and
      seizure type (p = 0.047). The best outcome was attained in patients with simple
      partial seizures. Co-medication with phenytoin was better than TGB +
      carbamazepine or TGB + valproic acid. The factor determining the presence of side
      effects was the rate of TGB dose increment during the first six weeks of
      treatment. Toxicity of TGB was not related to its target dose. Tiagabine is a
      safe and efficient anti-epileptic drug for children and adults with focal
      epilepsy. Efficacy of tiagabine treatment depends on the number of drugs
      administered since the epilepsy onset and on the type of seizures. A slow dose
      increment is crucial for safety of TGB treatment.

PMID- 14593752
TI  - [Quality of life of patients with multiple sclerosis].
AB  - The main aim of the paper was to evaluate quality of life in SM patients and to
      establish its determinants. Participants in the study were 50 patients
      hospitalized at the Neurology Ward in Gostynin-Kruk and 100 patients undergoing
      24-day rehabilitation in a sanatorium in Kowal. They were examined using the
      Functional Assessment of Multiple Sclerosis Quality of Life Questionnaire (FAMS)
      and a questionnaire concerning demographic data and the course of the disease,
      including the evaluation of motor disability level (EDSS, according to the
      Kurtzki scale). The group of patients at the Neurology Ward in Kruk consisted of
      20 men and 30 women (mean age 35.8 years, mean duration of the disease 9.1
      years). Their main source of income was paid employment (60%). In the Kowal
      sanatorium group there were 46 men and 54 women (mean age 44.6 years, mean
      duration of the disease 10.1 years). Their main source of income was disability
      pension (81%). In terms of the EDSS scale 56% of the Kruk patients represented
      the first level of motor disability (scores from 0.0 to 4.5), while 30% were
      classified as the second level (scores from 4.5 to 6.5). The proportions were
      reversed in the Kowal group: the second level (scores from 4.5 to 6.5) was
      represented by 57%, and the first level by 29% of the patients. Their quality of
      life (QoL) assessed by means of the FAMS scale was poor in 52% of cases and
      satisfactory in 48% of cases in the Kruk group, while in the Kowal group 35% of
      patients assessed their QoL as poor, and 59%--as satisfactory. The SM patients'
      quality of life was determined mainly by the degree of their motor self
      dependence.

PMID- 14593753
TI  - [Vagus nerve stimulation (VNS) in the treatment of drug-resistant epilepsy. A 4
      year follow-up evaluation of VNS treatment efficacy].
AB  - OBJECTIVES: Vagus nerve stimulation (VNS) is an alternative non-destructive
      surgical treatment for patients with medically intractable epilepsy. Neither the
      rationale nor proper indications for this treatment modality have been fully
      established yet. AIM OF THE STUDY: To assess the long-term efficacy of chronic
      VNS. MATERIAL: A series of 6 patients with drug-resistant epilepsy, subjected to
      VNS therapy. (4 females, 2 males, mean age 35.5 years, 3 patients with focal
      epilepsy, 3 with non-focal epilepsy, mean history of seizures 10 years, seizures
      frequency 10-400/per month). METHOD: An open-label prospective study with a 4
      year follow-up. RESULTS: At a 4-year follow-up one patient (with non-focal
      epilepsy) was seizure-free, with only rare episodes of aura (Engel Ia), while in
      another one (with bitemporal epilepsy) seizures frequency remained unchanged with
      VNS (Engel IVb). In the remaining 4 cases (one with bitemporal, one with
      parietal, and two with non-focal epilepsy) the mean overall reduction in seizures
      frequency as compared to the baseline was 60% (Engel IIIa). VNS resulted in a
      reduction of seizures by 90% in a patient with a history of an unsuccessful
      anterior callosotomy. CONCLUSIONS: 1. VNS was found to reduce both the frequency
      of seizures (an overall 60% reduction in seizures frequency) and the duration of
      post-seizure consciousness disturbances in focal and non-focal epilepsies, but
      seizures-free state could be obtained in only one out of six patients. 2. A
      previous unsuccessful callosotomy did not prevent a good anticonvulsant effect in
      one patient. 3. The anticonvulsant effect of VNS was cumulative over time during
      the first 3 years postoperatively, then it tended to reach a plateau. 4. The best
      clinical outcome was positively correlated with the currents 1.5-2.0 mA. No
      significant correlation was noted for the current adjustments at the level of 2.0
      3.5 mA. 5. Since no difference between the two stimulation patterns tested (30 s
      stimulation + 5 min break vs. 14 s + 3 min) was found as regards the
      anticonvulsant action of VNS, the latter pattern was subsequently used as the one
      more sparing the battery.

PMID- 14593754
TI  - [A comparison of neuro-endoscopic techniques with other surgical procedures in
      the treatment of arachnoid cysts in children].
AB  - The aim of the study was to evaluate the use of neuroendoscopic techniques (in
      comparison with other surgical procedures) in the treatment for arachnoid cysts
      in children. The analysis was performed on results of treatment 22 children with
      arachnoid cysts submitted to neuroendoscopic procedures. The group consisted of 6
      girls and 16 boys, aged from 1 day to 18 years (mean age 5.3 years, SD +/- 5.6).
      The control group treated with other, non-endoscopic surgical procedures
      consisted of 61 patients (20 girls and 41 boys aged from 10 days to 17 years,
      mean age 7 years, SD +/- 6). Criteria of success varied according to the type of
      surgical treatment. In the case of procedures other than shunt implantation, the
      treatment was regarded as effective, if there was no need to change the surgical
      method, while shunt implantation was considered effective, if shunt revision was
      not necessary. The operative treatment outcome was assessed using the Glasgow
      Outcome Scale. Post-treatment changes in the clinical state were graded as
      improvement, no change, or deterioration. In terms of the assumed criteria of
      success in the treatment for arachnoid cysts, neuroendoscopic procedures and
      microsurgical cyst excisions were among the most effective methods. As many as
      90.9% of neuroendoscopically treated children needed no other operation, in
      comparison with 92.6% of patients submitted to microsurgical procedures, who
      needed no change in the operative treatment. In the group of neuroendoscopically
      treated patients the effectiveness of neuroendoscopic operations varied according
      to the type of procedure used. Cystocysternostomies or cystoventriculostomies
      were successful in 100%. The analysis of clinical outcome has shown that
      deterioration was observed only in 13% of the patients with shunt implantation.
      Analyzing each type of arachnoid cyst separately, a statistically significant
      relationship was found between improvement of the clinical state and the use of
      craniotomy in the surgical treatment for cysts localized in the posterior fossa.
      Improvement in the case of neuroendoscopically treated children was related to a
      larger reduction in the cyst size after surgery and to a lower intensity of
      intraoperative bleeding. Neuroendoscopic techniques allowed to reduce the average
      period of hospitalization. Neuroendoscopic cystocysternostomy and
      cystoventriculostomy were the most effective techniques, besides microsurgical
      excision of arachnoid cysts. Neuroendoscopic treatment efficacy depends on the
      type of procedure used. The application of neuroendoscopic techniques allows to
      reduce the period of hospitalization.

PMID- 14593755
TI  - [Correlation of brain stem evoked response audiometry (BERA) with Glasgow Coma
      Scale (GCS) and Glasgow Outcome Scale (GOS)].
AB  - The diagnostic value of electric responses from the brain stem (BERA) in
      neurosurgical patients is still a matter for debate in the literature. Therefore
      in the study an attempt was made to determine the relationship between GCS scores
      and BERA recordings. Participants in the study were 64 patients with various
      types of brain damage. Evoked potentials from the brain stem were registered
      using the Hortmann BERAmodul apparatus. To facilitate the interpretation of
      results a special scale was developed for quantitative measurement of changes in
      BERA recordings. Abnormalities in BERA recordings were reflected in changes in
      GCS scores, and correlation between the two dimensions was found to be
      statistically significant. The relationship between BERA recordings and GOS
      scores was also significant: pathological changes in BERA recordings assessed as
      severe were associated with an unfavorable therapeutic outcome in the GOS. The
      presented findings indicate auditory evoked brain stem response (BERA) usefulness
      for objective evaluation of brain-damaged patients' clinical state.

PMID- 14593757
TI  - ["De novo" non-convulsive status epilepticus in adults and in the elderly].
AB  - There is a growing number of publications in the recent literature reporting the
      incidence of non-convulsive status epilepticus in the elderly, including both
      absence epilepsy and partial epileptic seizures. Absence status epilepticus
      creates a diagnostic problem because of its clinical features: confusion ranging
      from slight disorientation to stupor. Duration of such states may vary from one
      hour to a few weeks, with fluctuations and epileptic features in EEG recording (a
      typical pattern of spikes-slow waves, 3 Hz frequency, symmetrical and
      synchronical) that disappear after an intravenous injection of benzodiazepines.
      Absence status epilepticus can be evoked by toxic, metabolic or pharmacological
      factors as well as by convulsive epileptic seizures. Besides absence epileptic
      states of middle-cerebral origin there is a rising concern about absence status
      resulting from simple or complex partial seizures. Generalized non-convulsive
      status epilepticus following either simple partial or simple complex seizures is
      characterized by the presence of various focal signs associated with confusion,
      stupor or coma. The latter may be masking the clinical picture of an underlying
      cerebral pathology (e.g. brain tumor, hemorrhage, etc.), and epileptic changes
      can be seen in EEG recording only. Absence status epilepticus can occur in
      various forms of brain pathology, including stroke, brain tumors, traumatic
      lesions and other conditions, as well as in systemic diseases affecting the
      central nervous system function. Therefore, the authors emphasize the importance
      of electroencephalography in severely ill and unconscious patients, as well as
      the role of proper anti-epileptic treatment, as this may improve the outcome.

PMID- 14593756
TI  - [Pleomorphic xanthoastrocytoma: clinical symptoms, treatment, outcome].
AB  - Pleomorphic xanthoastrocytoma (PXA) is a very rare tumor of an astrocytic origin
      (prevalence rate: less than 1%). Four PXA cases studied by the authors are
      reported: one female and three male patients aged from 17 to 31 years. Seizure
      disorder was the initial presentation in all four cases--2 patients suffered from
      a single epileptic fit, while the other 2 patients had a long epileptic history
      of 6 and 25 years. CT and MRI scans revealed tumors located in the temporal (3
      cases) and parietal lobes (1 case). In 3 cases the tumor had a cystic part. All
      the patients underwent surgery--in all the cases a gross total removal was
      achieved. All four patients did well after surgery. Postoperative radiotherapy
      was administered in 2 cases. At a follow-up ranging from 9 months to 3.1 years
      all the patients remained in a good neurological condition, 3 of them were free
      from epilepsy, while one patient still suffered from epileptic seizures, but
      their frequency was lower. Observation of the PXA patients after the surgical
      treatment showed a good outcome--they were free from epileptic seizures.

PMID- 14593758
TI  - [Restless legs syndrome and periodic limb movements in sleep: pathophysiology and
      treatment].
AB  - The paper presents current views on the pathophysiology and treatment options in
      the restless legs syndrome (RLS) and periodic limb movements in sleep (PLMS).
      Moreover, concepts are outlined concerning possible involvement of various
      cerebral structures as well as neurotransmitter and metabolic systems in the RLS
      pathophysiology, with the focus on the role of dopamine and iron deficiency.
      Dopaminergic agents (i.e. L-dopa and dopamine agonists), currently regarded as
      the best therapeutic option in the treatment of RLS, are discussed in detail.
      Favorable outcomes attained in the treatment of RLS with the opioid receptor
      agonists, anticonvulsants, benzodiazepines, and adrenolytic agents are also
      reported.

PMID- 14593759
TI  - [Tetany as a difficult diagnostic problem in the neurological outpatient
      department].
AB  - The paper presents a model of diagnostic and therapeutic management of tetany,
      with special attention paid the role of magnesium and to psychotherapy or
      psychiatric treatment. Two types of tetany are distinguished: manifest and latent
      (spasmophilia). The former, due to hypocalcemia, is relatively rare and usually
      postoperative (parathyroid tetany), while the mechanism of the much more common
      latent tetany or spasmophilia involves hyperventilation and magnesium deficiency.
      Latent tetany affects particularly young women. There are many signs of
      spasmophilia, but none is specific, so this pathology is difficult to diagnose.

PMID- 14593760
TI  - [The current therapies for parkinson's disease. Part I: pharmacological
      treatment].
AB  - The following article presents current views on the possibility of
      pharmacological treatment of Parkinson's disease (PD). Research conducted on
      drugs with potentially neuroprotective effects has changed the way we viewed the
      treatment of early stages of PD. Beginning treatment with the application of
      dopamine agonists decreases the risk of the occurrence of motor complications,
      particularly high with young individuals. The treatment of advanced stages of the
      disease currently requires the application of levodopa combined with other
      medicines, such as dopamine agonists or catechol-O-methyl transferase (COMT)
      inhibitors. Selecting treatment options should be individualized for each
      patient; it should take into account the variability of the clinical picture
      dependent on the progression of the disease, and the possibility of the
      occurrence of undesirable adverse effects of the drugs prescribed.

PMID- 14593761
TI  - [Current therapies for parkinson's disease. Part II: surgical treatment].
AB  - Surgical treatment of Parkinson's disease (PD) is indicated in patients with
      severe neurological symptoms (tremor, bradykinesia, rigidity)--who do not benefit
      from nor tolerate pharmacological therapy. Surgery for PD modifies the motor
      system function by lesioning or electrostimulation of thalamic, pallidal or
      subthalamic nuclei. The technological progress together with refined CNS
      monitoring enabled wider application of deep brain stimulation (DBS). The
      efficacy of DBS is comparable with lesioning techniques (thalamotomy or
      pallidotomy) however bears less adverse effects. Both lesioning and DBS are
      generally well tolerated by patients. The side effects are mostly transient and
      neurological complications, if occur, usually do not affect quality of patient's
      life. Unfortunately, the modern surgery for PD is still very expensive and
      demanding for a large team of specialists and high technology.

PMID- 14593762
TI  - [Nucleoside analogs in the treatment of primary malignant brain tumors].
AB  - Standard therapeutic modalities including surgery, radio- and/or peripheral
      chemotherapy are ineffective in malignant gliomas. This is due to infiltration of
      distant brain areas by glioma cells and to the blood-brain barrier limiting
      penetration of anticancer drugs. One of the most promising experimental methods
      of glioma therapy is intracerebral implantation of biodegradable polymers
      containing cytotoxic compounds. This method allows to avoid peripheral toxicity
      of drugs. Considering that practically it is only malignant cells that
      proliferate in the brain, the use of drugs displaying selective toxicity toward
      DNA-replicating cells might help to avoid central toxicity as well. Several
      nucleoside analogs display selective cytotoxic and/or radiosensitizing effects on
      proliferating cells. Despite encouraging results obtained in the in vitro and
      animal models of gliomas, peripheral administration of these drugs turned out to
      be ineffective in the clinical settings. Intracerebral implantation of nucleoside
      analogs-containing biodegradable polymers may be much more efficacious,
      especially when combined with radiotherapy. Appropriate nucleoside analogs may
      also be employed in cell-selective radiotherapy and gene therapy of malignant
      gliomas.

PMID- 14593763
TI  - [Intra-arterial thrombolysis for acute angiographically proven occlusion in
      bifurcation of basilar artery. Case report].
AB  - In a 52 year-old male patient with a past history of two strokes, an occlusion of
      the basilar cerebral artery in the area of bifurcation into the posterior
      cerebral arteries was angiographically confirmed. Following an intra-arterial
      application of rt-PA a partial revascularization of the occluded posterior
      arteries was observed. After an interval of 8 hours rt-PA was administered again,
      resulting in a complete recanalization of the arteries. The patient's
      neurological state was stabilized but not improved, despite a systematic anti
      thrombotic treatment. His sudden death on the 23rd day of treatment was caused by
      pulmonary embolism. A postmortem examination indicated a complete patency of the
      Willis circle. The basilar artery was unchanged, while within the posterior
      cerebral arteries only a moderate thickening of the intima and a small dissection
      of the internal elastic membrane were found. There was no evidence of bleeding
      into the CNS. It was assumed that thrombolysis had resulted in a total
      revascularization of the occluded region and was uncomplicated. Ischemic changes
      within the nervous tissue had probably developed before the thrombolytic
      treatment, and were responsible for the lack of improvement. The patient's death
      due to pulmonary embolus in spite of the continued anticoagulant treatment, and
      his history of strokes in the young age, suggested the presence of some
      coagulation system abnormalities that could not be detected because of the
      thrombolytic and anticoagulant drugs administration.

PMID- 14593764
TI  - [Leber's hereditary optic neuropathy (LHON) with mutation at G3460A and MS-like
      phenotype].
AB  - A sporadic case of a 31 year-old woman with genetically confirmed diagnosis of
      LHON was presented. Both her optic nerves were affected, with a 5-year interval
      between the onset in one eye and the loss of vision in the second one. Besides
      optic atrophy clinical and laboratory signs of multiple sclerosis were found. A
      review of the literature suggests that the G3460A mutation present in this case
      rarely coexists with a MS-like clinical phenotype.

PMID- 14593765
TI  - [Stiff man syndrome successfully controlled with glucocorticoids and GABA-ergic
      drug administration: case report].
AB  - The stiff man syndrome is a rare CNS disease of a probably autoimmunologic
      etiology. The paper presents a case of a 45-year-old man hospitalized in our
      department of neurology because of trunk muscles rigidity and painful,
      paroxysmal, immobilizing muscle spasms with excessive sweating. On the
      neurological examination he presented with a restricted range of active movements
      of the trunk, increased muscle tone in the shoulder girdle, abdominal and
      paraspinal muscles, as well as lumbar hyperlordosis. The electromyographic needle
      examination revealed in all his trunk muscles an excess, continuous motor unit
      activity at rest, diminishing after benzodiazepine administration. This confirmed
      our initial diagnosis based on clinical symptoms and signs. No abnormalities were
      found in other examinations, including the cerebrospinal fluid analysis, CT of
      the brain, and the spinal cord MRI. The patient was treated with glucocorticoids
      and GABA-ergic drugs (vigabatrin, diazepam and baclofen) with good results, i.e.
      a considerable amelioration of his complaints. His motor ability has increased so
      much that he was fully self-dependent. No deterioration in his clinical status
      has been noted over three years since his discharge.

PMID- 14593766
TI  - [New radiotherapy techniques in the treatment of patients with craniopharyngioma:
      a report of two cases].
AB  - The authors report two cases of adult patients with craniopharyngioma recurrence
      after surgery. In both these patients radiotherapy resulted in a complete
      regression of the neoplasms, confirmed both by clinical examination and MR
      imaging. In both cases modern radiotherapy techniques were used so as to spare
      healthy tissues surrounding the tumor. Case 1. A 56-year-old man was admitted
      with an extensive (3.5 x 4.0 x 4.0 cm) recurrent craniopharyngioma 3 years after
      the initial surgery and 3 months after a surgery for relapse. Conformal 3-D
      planned fractionated radiotherapy to the total dose of 54 Gy in 30 fractions was
      delivered encompassing the tumor with 5 mm margins. Four months after
      radiotherapy MR imaging demonstrated a complete regression of the neoplasm and
      the patient recovered totally from his endocrine deficiency and neurological
      symptoms. Case 2. A 29-year-old man was irradiated 10 months after the initial
      surgery when a relapse of craniopharyngioma was found in MR imaging. The largest
      diameter of this recurrent tumor was 18 mm. The patient was subjected to
      fractionated stereotactic radiotherapy to the total dose of 54 Gy in 27
      fractions. Two months after the treatment his complete recovery was confirmed by
      MRI. Benefits resulting from the use of more recent radiotherapy techniques in
      the management of craniopharyngioma are discussed.

PMID- 14593767
TI  - [Training and practice of neurosurgery in USA-personal experience after two-year
      fellowship in University of Arizona].
AB  - Author describes his observations from two-year neurosurgical fellowship in
      University of Arizona, USA. During the fellowship he underwent rotations to
      Pediatric Neurosurgery Department at Phoenix Children's Hospital for one year,
      Neurosurgery Department at University Medical Center for six months, Neurosurgery
      Department at Veterans Affairs Hospital for three months and private neurosurgery
      group based on three separate hospitals for three months. Work in the particular
      departments is described as well as process of fellowship position obtainment and
      statistical data regarding fellowships and residences in neurosurgery in USA.

PMID- 14593768
TI  - [Principles of patient's indication for psycho-neurosurgical treatment].

PMID- 14593769
TI  - [Report on microsurgical approaches to brain, ventricles and skull practical
      course for neurosurgeons, Gainesville, Florida, USA, February 10-14, 2003].

PMID- 14593770
TI  - Evidence-based radiology problems. High-flow post-traumatic priapism:
      transcatheter embolotherapy: October 2003-September 2004.

PMID- 14593771
TI  - A practical approach to magnetic resonance imaging of normal and injured tendons:
      pictorial essay.

PMID- 14593772
TI  - Magnetic resonance imaging of bone tumours and mimics: pictorial essay.

PMID- 14593773
TI  - Magnetic resonance imaging of the growth plate: pictorial essay.

PMID- 14593774
TI  - The spectrum of ulnar collateral ligament injuries as viewed on magnetic
      resonance imaging of the metacarpophalangeal joint of the thumb.
AB  - OBJECTIVE: To elucidate the spectrum of ulnar collateral ligament (UCL) injuries
      detectable by magnetic resonance imaging (MRI). METHODS: Twenty-one patients (12
      male and 9 female, aged 14-62 years) with acute hyperabduction injuries of the
      first metacarpophalangeal joint underwent MRI for clinically suspected UCL
      injuries. All scans were performed in either a large-bore, 1.5-T imager or an
      experimental small-bore, 1.9-T imager. MRI findings and clinical evaluations of
      all patients and surgical reports of those who underwent surgery (n = 10) were
      reviewed and correlated retrospectively. RESULTS: A total of 6 patients
      demonstrated injuries that did not fall into previously described categories of
      UCL injuries and therefore illustrated the existence of a subclass of UCL
      injuries. We divided the MRI findings into 5 categories: Stener's lesions (n =
      6), moderately displaced (> or = 3 mm) complete tears (n = 5), minimally
      displaced (< 3 mm) complete tears (n = 4), nondisplaced complete tears (n = 3)
      and partial tears (n = 3). None of the MRI scans demonstrated a normal UCL.
      Although sensitivity and specificity were not calculated, only 2 cases
      demonstrated discordance between the MRI results and surgical findings or
      clinical outcomes. CONCLUSION: There is a spectrum of UCL injuries that have not
      previously been described.

PMID- 14593775
TI  - Residents' corner. Answer to case of the month #91. Leiomyosarcoma of the
      inferior vena cava with secondary Budd-Chiari syndrome.

PMID- 14593776
TI  - Residents' corner. Answer to case of the month #92. Septate uterus with
      longitudinal cervical and vaginal septum.

PMID- 14593777
TI  - Patient positioning after lung biopsy: further examination of conclusions.

PMID- 14593778
TI  - A short step from home.
AB  - Short-term care packages that integrate hospital services and primary care not
      only cut unnecessary admissions but enable older patients to recover in a setting
      more conducive to their well-being.

PMID- 14593779
TI  - Childhood atopic dermatitis: 2.

PMID- 14593780
TI  - Infusion devices: understanding the patient perspective to avoid errors.
AB  - The National Patient Safety Agency (NPSA) has sponsored a project to detect the
      root causes of problems with infusion devices and to identify ways of preventing
      errors. It is piloting a number of solutions in six trusts after a project that
      included a survey of patient views discovered the need for better communication
      and information for patients about this treatment method.

PMID- 14593781
TI  - Botulinum toxin: a deadly substance with great therapeutic effect.
AB  - Injections of botulinum toxin are commonly associated with cosmetic improvements.
      However, BTX is also used therapeutically to treat patients with neuromuscular
      and neurological disorders. Therapy is primarily carried out in outpatients as
      part of a wider management regimen, so it is vital for nurses to not only be
      aware of how BTX works but also of its deadly toxic properties.

PMID- 14593782
TI  - Patient care advisers: helping cardiac surgery patients to exercise choice.
AB  - Cardiac surgical centres have received funds to appoint at least one patient care
      adviser as part of the Government's Patient Choice Initiative. Mostly from a
      nursing background, their role is to ensure patients who have been waiting more
      than six months have the choice of receiving surgery sooner at another centre.
      This paper describes this national initiative.

PMID- 14593783
TI  - A nurse-led community scheme for managing patients with COPD.
AB  - This paper describes the development of a community-based scheme for patients
      with chronic obstructive pulmonary disease. The nurse-led scheme, which involves
      making regular visits to patients to help them manage their condition at home and
      to provide support and education, has resulted in early detection of problems and
      a reduction in hospital admissions.

PMID- 14593784
TI  - Protocol-based care: 2. Developing pathways with effective teams.
AB  - An integrated care pathway aims to ensure quality of care. A successful model
      hinges on the strength of the multidisciplinary ICP team and its members' ability
      to work together. Part two of this 12-part series focuses on how one topic--acute
      coronary syndrome--was chosen at one trust, and highlights the experiences of
      setting up a multidisciplinary cardiac care ICP team.

PMID- 14593785
TI  - Developing a patient pathway to deliver a new oral chemotherapy.
AB  - Introducing service delivery changes is rarely straightforward and requires
      careful planning. This paper reports on the work involved in preparing for, and
      implementing, an oral chemotherapy programme to be delivered on an outpatient
      basis. It outlines the involvement of both hospital and community staff and
      stresses the importance of providing patients with information.

PMID- 14593786
TI  - A case study to demonstrate the role of proteases in wound healing.
AB  - Proteases play an important role in regulating the balance between tissue
      synthesis and degradation. However, in chronic wounds, this regulation may be
      defective and healing problems will result. This paper presents a case study
      detailing the use of a protease-modulating matrix (Promogran) on a chronic wound.
      First, the concept of wound healing is discussed.

PMID- 14593787
TI  - The place of pharmacotherapy products in smoking cessation.
AB  - More people are giving up smoking with the support of nicotine replacement
      therapies or the former antidepressant bupropion than without, according to a
      growing body of evidence. This paper looks at the evidence supporting the use of
      pharmacotherapy products and explains the options available, as well as
      considering the nurse's role in helping people quit.

PMID- 14593788
TI  - Patient information: Part 2. Planning an information package.
AB  - In the second article of this series we look at the planning stage of a project
      to produce patient information and the factors that should be considered. The
      paper also discusses guidelines for the production of patient information and
      legal aspects of information provision.

PMID- 14593789
TI  - Kentucky breast cancer report card.
AB  - The Kentucky Breast Cancer Task Force in conjunction with the Kentucky Cancer
      Registry and the Kentucky Cancer Program has prepared a Breast Cancer Report Card
      concerning the incidence and mortality of this disease among Kentucky women for
      the period of 1995 to 2000. Comparison of Kentucky data with those from the
      Surveillance, Epidemiology and End Results (SEER) program of the National Cancer
      Institute reveals that the incidence rate of breast cancer in Kentucky is lower
      than that for the SEER population. The incidence of "early" stage disease is
      significantly lower among Kentucky women, but the incidence of "late" stage
      disease is similar in both data sets. The incidence rate is lower in rural than
      urban Kentucky, and is lowest in rural Appalachian Kentucky. The ratio of "early"
      to "late" stage breast cancer is lower for Kentucky women than for the SEER
      population and lowest in women over age 65, the group in which approximately half
      of the new cases of breast cancer are detected each year. Mortality rates are
      similar for Kentucky and for the SEER population. Improving the breast cancer
      mortality rate in Kentucky will depend on increased case-finding of "early" stage
      disease and increasing the ratio of "early" to "late" stage incident cases.

PMID- 14593790
TI  - Rural-urban variation in breast-conserving surgery in Kentucky.
AB  - Recently researchers from the University of Kentucky published a study showing
      that, in the early 1990s, Appalachian women were less likely to receive breast
      conserving surgery (BCS) in the treatment of early stage cancer, than other
      Kentucky women diagnosed with early stage breast cancer, and that poverty was the
      only predictor of lowered probability of receiving BCS. In that study, analyses
      were performed on a dataset of Kentucky Medicare beneficiary claims of treatment
      information that had been linked with data from the Kentucky Cancer Registry for
      staging information. County-level data were also used, from the 1990 census and
      other sources, on poverty and education rates for women, and hospital bed and
      physician ratios per population. While the findings of the study are significant,
      the study is generalizable only to women aged 65 years and older because a
      Medicare dataset was used. In addition, the study represented Kentucky practice
      seven to ten years ago, from 1992 through 1995, which raises interest in
      obtaining BCS rates for more current practice. In this article, we update the
      previous study with the most recent data on BCS, and include women of all ages,
      not just those over age 64 years. Access was obtained to the Kentucky Cancer
      Registry, which contains records of the initial treatment for breast cancer, as
      well as staging information about the extent of disease at diagnosis. Data from
      the 2000 census were not available for this analysis, however.

PMID- 14593791
TI  - The battle of the bulge.

PMID- 14593792
TI  - Characteristics of sexual homicides committed by psychopathic and nonpsychopathic
      offenders.
AB  - In this study, the relationship between psychopathy and the prepetration of
      sexual homicide was investigated. The official file descriptions of sexual
      homicides committed by 18 psychopathic and 20 nonpsychopathic Canadian offenders
      were coded (by coders unaware of Psychopathy Checklist--Revised [PCL--R] scores)
      for characteristics of the victim, victim/perpetrator relationship, and evidence
      of gratuitous and sadistic violent behavior. Results indicated that most (84.7%)
      of the sexual murderers scored in the moderate to high range on the PCL--R. The
      majority of victims (66.67%) were female strangers, with no apparent influence of
      psychopathy on victim choice. Homicides committed by psychopathic offenders
      (using a PCL--R cut-off of 30) contained a significantly higher level of both
      gratuitous and sadistic violence than nonpsychopathic offenders. Most (82.4%) of
      the psychopaths exhibited some degree of sadistic behavior in their homicides
      compared to 52.6% of the nonpsychopaths. Implications for homicide investigations
      are discussed.

PMID- 14593793
TI  - Juror sensitivity to the cross-race effect.
AB  - Black and White mock jurors' sensitivity to the cross-race effect was
      investigated by varying the race of the eyewitness in a simulated murder trial of
      a Black defendant. Participants heard an audiotape of a trial after which they
      rendered a verdict and rated the credibility of the witnesses. White participants
      found the prosecution witnesses (including the eyewitness) more credible, and the
      defense witness less credible, than did Black participants; they were also more
      likely to find the defendant guilty. The Black eyewitness was perceived as more
      credible than was the White eyewitness, but eyewitness race had no effect on
      verdict. These results are consistent with the literature indicating that jurors
      of different races reach different verdicts, and also that jurors are relatively
      insensitive to factors that affect eyewitness testimony, such as the cross-race
      effect.

PMID- 14593794
TI  - Eyewitness memory, suggestibility, and repeated recall sessions in children with
      mild and moderate intellectual disabilities.
AB  - This study of eyewitness memory questioned children with mild and moderate
      intellectual disabilities (ID) about a live staged event 1 day later and, again,
      2 weeks later. Children with mild ID performed as well as typically-developing
      children of the same age in response to free recall instructions, and they were
      just as able as same age peers to resist misleading questions. However, they
      performed more poorly on general questions, probing for further information after
      free recall. The children with mild ID also changed their responses to specific
      questions more often in the repeated interview. The group of children with
      moderate ID showed markedly lower performance than peers of the same age on
      nearly every type of eyewitness memory question. Comparisons of the children with
      ID to mental age-matched peers indicated that performance was similar, although
      children with ID gave more information in response to free recall instructions
      and changed their answers in the repeated interview more often. Standardized
      measures of verbal memory (TOMAL) and suggestibility (Gudjonsson Suggestibility
      Scale) were modest to moderate predictors of eyewitness memory performance.

PMID- 14593795
TI  - Perceptions of older adult eyewitnesses: will you believe me when I'm 64?
AB  - Participant-witnesses (young adults/young seniors/older seniors) viewed one of
      two versions of a simulated videotaped crime (crime context either familiar to
      young or older adults). The witnesses were videotaped responding to direct and
      cross-examination questions about the video. The older seniors were significantly
      less accurate than the young adults and young seniors. Familiarity of the crime
      context did not affect testimony accuracy. However, the older seniors were more
      verbose when describing a familiar context. Participant-jurors viewed the
      testimony videotapes and evaluated the witnesses' credibility. All witnesses were
      regarded as equally credible in testifying and less accurate in response to cross
      examination questioning.

PMID- 14593796
TI  - Eyewitness accuracy rates in police showup and lineup presentations: a meta
      analytic comparison.
AB  - Meta-analysis is used to compare identification accuracy rates in showups and
      lineups. Eight papers were located, providing 12 tests of the hypothesis and
      including 3013 participants. Results indicate that showups generate lower
      choosing rates than lineups. In target present conditions, showups and lineups
      yield approximately equal hit rates, and in target absent conditions, showups
      produce a significantly higher level of correct rejections. False identification
      rates are approximately equal in showups and lineups when lineup foil choices are
      excluded from analysis. Dangerous false identifications are more numerous for
      showups when an innocent suspect resembles the perpetrator. Function of lineup
      foils, assessment strategies for false identifications, and the potential impact
      of biases in lineup practice are suggested as additional considerations in
      evaluation of showup versus lineup efficacy.

PMID- 14593797
TI  - Predicting institutional adjustment and recidivism with the psychopathy checklist
      factor scores: a meta-analysis.
AB  - This study explored the validity of the PCL/PCL-R factor scores in predicting
      institutional adjustment and recidivism in forensic clients and prison inmates.
      Forty-two studies in which institutional adjustment, release outcome
      (recidivism), or both were assessed prospectively with the PCL/PCL-R yielded 50
      effect size estimates between the PCL/PCL-R factor scores and measures of
      institutional adjustment/recidivism. A meta-analysis of these findings disclosed
      that Factor 2 (Antisocial/Unstable Lifestyle) correlated moderately well with
      institutional adjustment and recidivism, whereas Factor 1
      (Affective/Interpersonal Traits) was less robustly associated with these
      outcomes. Direct comparisons of the mean effect sizes attained by Factors 1 and 2
      revealed that Factor 2 was significantly more predictive of total outcomes,
      general recidivism, violent recidivism, and outcomes from the 12 most
      methodological sound studies than Factor 1. There was less differentiation
      between Factors 1 and 2 on measures of institutional adjustment.

PMID- 14593799
TI  - Purification and characterization of beta-N-acetylhexosaminidase from maize
      seedlings.
AB  - Enzymatic activity of beta-N-acetyhexosaminidase (EC 3.2.1.52) was analysed in
      seeds and young seedings of maize (Zea mays) using di-N-acetylchitobiose as a
      substrate. Substantial activity was detected in dry seeds. Activity increased
      before germination (48 h) but exclusively in the embryo. In seedlings, most of
      the activity was found in the scutellum, and lower levels in shoots and roots
      immediately after germination. An isoform of the enzyme was purified from
      scutellum (72 h after the start of imbibition) by heat treatment of crude extract
      and four steps of chromatography. Purified beta-N-acetyl-hexosaminidase showed a
      single band on SDS-PAGE of around 70 kDa. This was almost the same as the
      molecular weight estimated by size exclusion chromatography, indicating a
      monomeric form of the active enzyme. The relative activity of the enzyme for di-N
      acetylchitobiose was about 15 times greater than that for p-nitrophenyl-N
      acetylglucosaminide or p-nitrophenyl-N-acetylgalactosaminide. Analysis of the
      reaction with oligo-N-acetylchitooliogsaccharides [(GlcNAc)n] revealed an exotype
      enzyme producing predominantly (GlcNAc)n-1 and N-acetylglucosamine. The optimum
      pH, temperature, and isoelectric point (pl) were 4.5, 55 degrees C, and 6.75,
      respectively. The activity was almost completely inhibited in the presence of 5
      mmol/L Ag+, Hg2+, or Fe3+.

PMID- 14593798
TI  - Maize DNA polymerase alpha is phosphorylated by a PCNA-associated cyclin/Cdk
      complex: effect of benzyladenine.
AB  - The activity of maize DNA polymerases 1 and 2 (delta and alpha-type enzymes,
      respectively) is stimulated during germination if embryo axes are imbibed in the
      presence of benzyladenine. In vivo, DNA pol 2 is a phosphorotein that appears to
      be maximally phosphorylated previous to the S phase start time (by 12 h of
      germination, Coello and Vazquez-Ramos 1995a). We find that, in vitro, a PCNA
      associated cyclin/kinase activity isolated from maize axes acquires an increasing
      capacity to phosphorylate DNA pol 2 as germination advances; moreover, the PCNA
      associated kinase isolated from BA-treated maize axes germinated at 3 h
      phosphorylates DNA pol 2 at the same level observed in samples of axes germinated
      for 13 h in the absence of exogenous BA. PCNA-associated kinase activity from BA
      treated axes germinated at 13 h maximal using DNA pol 2 as substrate. However,
      there is no modification in DNA polymerase activity as a consequence of protein
      phosphorylation. Results are discussed in terms of their significance for cell
      cycle regulation during seed germination.

PMID- 14593800
TI  - Heat shock protein synthesis is induced by diethyl phthalate but not by di(2
      ethylhexyl) phthalate in radish (Raphanus sativus).
AB  - The toxicity and effects on protein synthesis of the phthalate esters diethyl
      phthalate (DEP) and di(2-ethylhexyl) phthalate (DEHP) was studied in radish
      seedings (Raphanus sativus cv. Koopenhaminan tori). Phthalate esters are a class
      of commercially important compounds used mainly as plasticizers in high molecular
      weight polymers such as many plastics. They can enter soil through various routes
      and can affect plant growth and development. First the effect of DEP and DEHP on
      the growth of radish seedings was determined in an aqueous medium. It was found
      that DEP, but not DEHP, caused retardation of growth in radish. A further
      investigation on protein synthesis during DEP-stress was executed by in vivo
      protein labeling combined with two-dimensional gel electrophoresis (2D-PAGE). For
      comparisons with known stress-induced proteins a similar experiment was done with
      heat shock, and the induced heat shock proteins (HSPs) were compared with those
      of DEP-stress. The results showed that certain HSPs can be used as an indicator
      of DEP-stress, although the synthesis of most HSPs was not affected by DEP. DEP
      also elicited the synthesis of numerous proteins found only in DEP-treated roots.
      The toxic effect of phthalate esters and the roles of the induced proteins are
      discussed.

PMID- 14593801
TI  - Effect of partial root excision on shoot water relations.
AB  - Removing 4 out of 5 serminal roots from 7-day-old wheat seedlings arrested leaf
      elongation for 1.5 h. This effect can be explained by an initial decrease in
      foliar water content resulting from the smaller root surface area available for
      water uptake. Subsequently, leaf hydration increased with time and came to equal
      that of intact plants within 2 h. The rehydration was seemingly effected by an
      increasing conductivity of the one remaining root axis, since transpiration of
      the partially de-rooted plants did not fall below that of controls. With time,
      leaf elongation resumed, but at a slower rate than in intact plants. This slower
      growth may be attributed to a decrease in leaf extensibility since this was found
      to be reduced when measured by a counterweight technique involving linear
      displacement transducers. Loss of extensibility was associated with decreased IAA
      concentration in the leaf elongation zone.

PMID- 14593802
TI  - Photosynthesis and photoprotection in Nicotiana tabacum L. in vitro-grown
      plantlets.
AB  - Nicotiana tabacum L. plantlets were cultured in vitro photoautotrophically (0%
      sucrose) and photomixotrophically (3% or 5% sucrose) at two irradiances (80 or
      380 mumol m-2 s-1) with the aim of investigating the effect of these culture
      conditions on photosynthetic parameters and on protective systems against excess
      excitation energy. In plantlets grown photoautotrophically under higher
      irradiance photoinhibition was demonstrated. These plantlets had a decreased
      chlorophyll (Chl) a + b content and Chl a/b ratio, an increased content of
      xanthrophyll cycle pigments and a higher deepoxidation state, a decreased maximum
      photochemical efficiency of photosystem II (PS II) and actual photochemical
      efficiency of PS II, and an increased non-photochemical quenching. In the
      photoautotrophically grown plantlets and those photomixotrophically grown with 3%
      sucrose, the increase of growth irradiance from 80 to 380 mumol m-2 s-1
      stimulated the activities of ascorbate-glutathione cycle enzymes with the
      exception of ascorbate peroxidase. Ascorbate peroxidase activity was not affected
      by the increase in growth irradiance but a significant decrease with increasing
      sucrose concentration was evident. The higher concentration of sucrose in the
      medium (5%) in combination with the higher irradiance inhibited photosynthesis
      (decrease in Chl a + b content and net photosynthetic rate) but no significant
      changes in activities of ascorbate-glutathione cycle enzymes were found. These
      results suggest that exogenous sucrose added to the medium improved high
      irradiance and oxidative stress resistance of the plantlets but the effect of
      sucrose is concentration dependent.

PMID- 14593803
TI  - Determination of phenolic antioxidant compounds produced by calli and cell
      suspensions of sage (Salvia officinalis L.).
AB  - Sage (Salvia officinalis L.) calli were established by culturing internodal
      segments, excised from aseptic seedlings, on MS basal medium gellied with agar
      and supplemented with 0.05 mg/L dichlorophenoxyacetic acid (2,4-D) in presence of
      benzyladenine (BA) or zeatin (ZEA) or kinetin (KIN), at 1.5 mg/L. Suspended cells
      were established by transferring one callus to 50 mL of liquid MS basal medium
      devoid of agar and containing the same type of hormonal supplementation used in
      respective calli growth. The highest growth of calli and suspensions occurred
      with 1.5 mg/L ZEA. However, with this cytokinin supplementation, as well as with
      1.5 mg/L KIN, both in presence of 0.05 mg/L 2,4-D, suspensions differentiated
      small root shaped structures. Well shaped, majority single cell suspensions were
      formed under the effect of 0.05 mg/L 2,4-D and 0.5 mg/L KIN. Calli grown with
      0.05 mg/L 2,4-D and 1.5 mg/L BA and suspended cells grown with 0.05 mg/L 2,4-D
      and ZEA or KIN at 1.5 mg/L, or KIN at 0.5 mg/L, were searched for phenolics
      production. Twelve phenolic compounds were identified in calli: gallic acid, 3-O
      caffeoylquinic acid, 5-O-caffeoylquinic acid, caffeic acid, rosmarinic acid,
      hesperetin, epirosmanol, hispidulin, genkwanin, carnosol, carnosic acid, and
      methyl carnosate. With the exception for genkwanin and epirosmanol all of these
      phenolic compounds were also produced by the sage suspension cultures grown in
      the presence of 1.5 or 0.5 mg/L KIN. Genkwanin was the only phenolic absent in
      the suspensions grown with 1.5 ZEA. Suspended cells, grown with 0.5 mg/L KIN, and
      calli cultures showed the highest specific accumulation of the total phenolics,
      with rosmarinic acid representing 94-97%.

PMID- 14593804
TI  - Differential responses in vitro of rice cultivars to Italian lineages of the
      blast pathogen Pyricularia grisea (Cooke) Sacc. 1. Oxidative burst.
AB  - Suspension cultured cells of six rice cultivars differing in their sensitivity to
      blast were treated with mycelial wall hydrolysates prepared from seven isolates
      belonging to different Pyricularia grisea lineages. Soon after elicitor addition,
      rice cells produced significant amounts of superoxide anion, which was rapidly
      converted into diffusible peroxide. Maximal effects were achieved at 50 mg L-1
      elicitor. In all cases, a 7 to 13-fold increase in the basal rate of reactive
      oxygen species production was found. Neither differential effects among strains
      nor clear relationships between lineage and the resulting oxidative burst were
      evident. Interestingly, a good correlation was found between basal (and elicited)
      levels of peroxide generation and the overall tolerance of rice cultivars to the
      pathogen. About two days after elicitation, cell death occurred proportional to
      the amount of hydrogen peroxide released. Peroxide was required to trigger loss
      of cell viability, but the latter was not due to a direct toxic effect,
      suggesting the induction of programmed cell death. Results represent the first
      data aimed to develop in vitro tests for pathogenicity prediction of Italian
      blast lineages toward rice cultivars.

PMID- 14593806
TI  - Ultra-structural and functional changes in the chloroplasts of detached barley
      leaves senescing under dark and light conditions.
AB  - Changes in the chloroplast ultra-structure and photochemical function were
      studied in detached barley (Hordeum vulgare L. cv. Akcent) leaf segments
      senescing in darkness or in continuous white light of moderate intensity (90
      mumol m-2 s-1) for 5 days. A rate of senescence-induced chlorophyll degradation
      was similar in the dark- and light-senescing segments. The Chl a/b ratio was
      almost unchanged in the dark-senescing segments, whereas in the light-senescing
      segments an increase in this ratio was observed indicating a preferential
      degradation of light-harvesting complexes of photosystem II. A higher level of
      thylakoid disorganisation (especially of granal membranes) and a very high lipid
      peroxidation were observed in the light-senescing segments. In spite of these
      findings, both the maximal and actual photochemical quantum yields of the
      photosystem II were highly maintained in comparison with the dark-senescing
      segments.

PMID- 14593805
TI  - Changes in some enzymes of microbodies and plastid development in excised radish
      cotyledons: effect of narciclasine.
AB  - Narciclasine (NCS), isolated from mucilage of Narcissus bulb, showed inhibitory
      effects on growth and plastid development of excised radish cotyledons. NCS (0.1
      mumol/L) started to show inhibitory effects on isocitrate lyase and
      hydroxypyruvate reductase activities after 24 h incubation in light. When NCS
      concentration was increased to 10 mumol/L, the activities of both enzymes are
      completely inhibited. From ultrastructural studies, NCS markedly prevented the
      degradation of protein bodies and lipid bodies, as well as chloroplast formation
      of excised radish cotyledons. There was only little degradation of protein and
      lipid bodies, and almost no chloroplast formation in the excised radish cotyledon
      treated with 1 mumol/L NCS. Therefore, our results provide clear evidence that
      NCS inhibited the transition of glyoxysomes and peroxisomes, and chloroplast
      development.

PMID- 14593807
TI  - Stimulatory effect of cytokinins and interaction with IAA on the release of
      lateral buds of pea plants from apical dominance.
AB  - Lateral buds of pea plants can be released from apical dominance and even be
      transformed into dominant shoots when repeatedly treated with synthetic exogenous
      cytokinins (CKs). The mechanism of the effect of CKs, however, is not clear. The
      results in this work showed that the stimulatory effects of CKs on the growth of
      lateral buds and the increase in their fresh weights in pea plants depended on
      the structure and concentration of the CKs used. The effect of N-(2-chloro-4
      pyridyl)-N'-phenylurea (CPPU) was stronger than that of 6-benzylaminopurine (6
      BA). Indoleacetic acid (IAA) concentration in shoot, IAA export out of the
      treated apex and basipetal transport in stems were markedly increased after the
      application of CPPU or 6-BA to the apex or the second node of pea plant. This
      increase was positively correlated with the increased concentration of the
      applied CKs. These results suggest that the increased IAA synthesis and export
      induced by CKs application might be responsible for the growth of lateral shoots
      in intact pea plants.

PMID- 14593808
TI  - Influence of temperature on biomass, iron metabolism and some related
      bioindicators in tomato and watermelon plants.
AB  - Tomato, Lycopersicon esculentum L. cv. RX-335, and watermelon plants, Citrullus
      lanatus [Thom.] Mansf. cv. F-90 were grown under controlled conditions at three
      different temperatures (10 degrees, 25 degrees and 35 degrees C) for 30 days. The
      aim of the experiment was to analyse the effect of the different temperatures on
      Fe uptake and distribution, as well as the behaviour of the main bioindicators of
      this element. Thus, we analysed the total and free Fe concentrations and H2O2
      concentrations, as well as enzymatic activities of Fe-chelate reductase (FeCH-R),
      aconitase (Aco), guaiacol peroxidase (GPX), catalase (CAT), and Fe-superoxide
      dismutase (FeSOD), and the dry weight of the plants. The effect caused by each
      temperature varied according to the species of plant. Our results indicate that
      heat stress appears in tomato plants when grown at 35 degrees C (above the
      optimal temperature for growth), while in watermelon plants, which need more heat
      than do tomatoes, cold stress appears at 10 degrees C (below the optimal
      temperature for growth). Despite these differences between the two species, the
      results under conditions of thermal stress were the same: 1) decreased shoot
      weight, 2) reduced Fe uptake, 3) depressed activities of FeCH-R, Aco, GPX, CAT
      and 4) boosted SOD activity. In short, our results appear to indicate that,
      whether heat in tomato plants or cold stress in watermelon plants, Fe uptake was
      diminished, as were the enzymatic activities related to the levels of this
      micronutrient in the plant. The high FeSOD activity in these plants could be
      explained by a defensive response to heat or cold stress.

PMID- 14593809
TI  - Arbuscular mycorrhizal fungi influence water relations, gas exchange, abscisic
      acid and growth of micropropagated chile ancho pepper (Capsicum annuum) plantlets
      during acclimatization and post-acclimatization.
AB  - Little is known about the role of arbuscular mycorrhiza fungi (AMF) on
      physiological changes of micropropagated plantlets during acclimatization and
      post-acclimatization. Using chile ancho pepper (Capsicum annuum L. cv. San Luis),
      measurements were made of water relations, gas exchange, abscisic acid (ABA),
      plantlet growth and AMF development. Plantlets had low photosynthetic rates (A)
      and poor initial growth during acclimatization. Relative water content (RWC)
      decreased during the first days after transfer from tissue culture containers to
      ex vitro conditions. Consequently, transpiration rates (E) and stomatal
      conductance (gs) declined, confirming that in vitro formed stomata were
      functional and able to respond ex vitro to partial desiccation--thus avoiding
      excessive leaf dehydration and plant death. Colonization by AMF occurred within 3
      days after inoculation. Colonized plantlets had lower leaf ABA and higher RWC
      than noncolonized (NonAMF) plantlets during peak plant dehydration (6 days after
      plant transfer)--and a higher A and gs as early as days 5 and 7. During post
      acclimatization [after day 8, when RWC increased and stabilized], A increased in
      all plantlets; however, more dramatic changes occurred with AMF plantlets. Within
      48 days, 45% of the roots sampled of inoculated plantlets were colonized and had
      extensive arbuscule development. At this time, AMF plantlets also had greater E,
      A, leaf chlorophyll, leaf elemental N, P and K, leaf dry biomass and leaf area,
      fruit production and differences in carbon partitioning [lower root/shoot ratio
      and higher leaf area ratio] compared with NonAMF plantlets. Rapid AMF
      colonization enhanced physiological adjustments, which helped plantlets recover
      rapidly during acclimatization and obtain greater growth during post
      acclimatization.

PMID- 14593811
TI  - Changes in oxidative stress enzymes during artificial ageing in cotton (Gossypium
      hirsutum L.) seeds.
AB  - The present study was carried out to elucidate the mechanism of seed
      deterioration in two cotton (Gossypium hirsutum L.) cultivars (HS6 and H1098).
      The seeds were artificially aged at 40 +/- 1 degree C and 100% relative humidity
      for 4 days. In both cultivars, germinability decreased, whereas membrane
      deterioration, as assayed by electrical conductivity of the seed leachates,
      increased progressively with artificial ageing. The decrease in germinability was
      well correlated with increased accumulation of total peroxide and malondialdehyde
      content and decreased activities of antioxidant enzymes peroxidase, catalase,
      ascorbate peroxidase, glutathione reductase and superoxide dismutase.
      Hydropriming for 2 h and ascorbic acid priming for 12 h partially maintained
      germination and the activities of various antioxidant enzymes under artificial
      ageing and the accumulation of peroxide and MDA content was decreased. The
      results suggest that cotton seed deterioration during accelerated ageing is
      closely related to a decrease in activities of various peroxide scavenging
      enzymes and to lipid peroxidation.

PMID- 14593810
TI  - Role of 5-aminolevulinic acid (ALA) on active oxygen-scavenging system in NaCl
      treated spinach (Spinacia oleracea).
AB  - ALA is a key precursor in the biosynthesis of porphyrins such as chlorophyll and
      heme, and was found to induce temporary elevations in the photosynthesis rate,
      APX, and CAT; furthermore, treatment with ALA at a low concentration might be
      correlated to the increase of NaCl tolerance of spinach plants. The
      photosynthetic rate and the levels of active oxygen-scavenging system in the 3rd
      leaf of spinach (Spinacia oleracea) plants grown by foliar treatment with 0,
      0.18, 0.60 and 1.80 mmol/L 5-aminolevulinic acid under 50 and 100 mmol/L NaCl
      were analyzed. Plants treated with 0.60 and 1.80 mmol/L ALA showed significant
      increases in the photosynthetic rate at 50 and 100 mmol/L NaCl, while that of
      0.18 mmol/L ALA did not show any changes at 50 mmol/L NaCl and a gradual decrease
      at 100 mmol/L NaCl. In contrast, the rate with 0 mmol/L ALA showed reduction at
      both concentrations of NaCl. The increase of hydrogen peroxide content by
      treatment with 0.60 and 1.80 mmol/L ALA were more controlled than that of 0
      mmol/L ALA under both NaCl conditions. These ALA-treated spinach leaves also
      exhibited a lower oxidized/reduced ascorbate acid ratio and a higher
      reduced/oxidized glutathione ratio than the 0 mmol/L-treated spinach leaves when
      grown at both NaCl conditions. With regard to the antioxidant enzyme activities
      in the leaves, ascorbate peroxidase, catalase, and glutathione reductase
      activities were enhanced remarkably, most notably at day 3, by treatment with
      0.60 and 1.80 mmol/L ALA under both NaCl conditions in comparison to that of 0
      and 0.18 mmol/L ALA. These data indicate that the protection against oxidative
      damage by higher levels of antioxidants and enzyme activities, and by a more
      active ascorbate-glutathione cycle related to the increase of the photosynthesis
      rate, could be involved in the increased salt tolerance observed in spinach by
      treatment with 0.60 to 1.80 mmol/L ALA with NaCl.

PMID- 14593812
TI  - Construction of gene expression system in hop (Humulus lupulus) lupulin gland
      using valerophenone synthase promoter.
AB  - The promoter region of the valerophenone synthase (VPS) gene was isolated from
      hop (Humulus lupulus). VPS, a member of the chalcone synthase (CHS) super-family,
      catalyzes the biosynthesis reaction of the hop resin that significantly
      accumulates in the cone's secretory gland called the "lupulin gland". The typical
      H-box and G-box sequences, which exist in many plants' CHS promoters and act as
      cis-elements for tissue specificity, UV-light induction, etc., were not found in
      the isolated VPS promoter, although the H-box-like sequence (CCTTACC, CCTAACC)
      and the core sequence (ACGT) of the G-box were observed. The transformation
      experiment using the VPS promoter-UIDA gene fusion revealed that the promoter
      acts not only in the lupulin gland but also in the glands of leaf and stem. On
      the other hand, the VPS promoter activity was not induced by UV-irradiation.

PMID- 14593813
TI  - Peach (Prunus persica L.) fruit growth and ripening: transcript levels and
      activity of polyamine biosynthetic enzymes in the mesocarp.
AB  - Transcript levels and activities of the polyamine biosynthetic enzymes arginine
      decarboxylase (ADC, EC 4.1.1.19), ornithine decarboxylase (ODC, EC 4.1.1.17) and
      S-adenosylmethionine decarboxylase (SAMDC, EC 4.1.1.21), as well as free
      polyamine titres, were analysed throughout the four growth stages S1-S4 leading
      up to ripening in the mesocarp from peach fruit (Prunus persica L. Batsch cv.
      Redhaven) grown under field conditions. SAMDC mRNA, which was northern analysed
      by using a PCR-generated homologous SAMDC probe, and ADC mRNA levels appeared
      quite stable during fruit development, while ODC transcript accumulation showed a
      discontinuous trend. The pattern of transcript levels during growth did not
      correlate with that of the relative enzyme activity, which instead correlated
      well with free polyamine levels. Both exhibited maximum levels in S1 and a
      smaller peak in S3. The behaviour of the polyamine biosynthetic machinery is
      discussed in relation to the different cell growth rates occurring during fruit
      development.

PMID- 14593814
TI  - Stimulation of betacyanin synthesis through exogenous methyl jasmonate and other
      elicitors in suspension-cultured cells of Portulaca.
AB  - Betacyanin production in suspension-cultured cells of Portulaca was significantly
      enhanced by both abiotic and biotic elicitors. Betacyanin levels increased 1.3
      and 1.5-fold over the controls in the presence of two abiotic elicitors (20
      mumol/L CuSO4 and 100 mumol/L FeEDTA) and increased 1.8 and 1.6-fold in the
      presence of two biotic elicitors (0.5 mg/L beta-glucan and 0.5 mg/L chitosan).
      Maximum betacyanin synthesis with the two most effective elicitors was obtained
      when cultures were treated on day 1 and day 0 by beta-glucan and FeEDTA,
      respectively. A concentration-dependent response was exhibited by cultures
      treated with exogenous methyl jasmonate (MJ). MJ alone at 0.1 mumol/L caused a
      2.6-fold increase in betacyanin synthesis when administered to the suspension
      culture on day 3. However, no additive effect on betacyanin accumulation was
      observed in treatments, which combined MJ and beta-glucan or FeEDTA. Treatment
      with ibuprofen (IB), an inhibitor of jasmonate biosynthesis, reduced the level of
      betacyanin in cells cultured in standard medium at all concentrations tested (25,
      50, 100 mumol/L). The effect of IB on betacyanin synthesis in the cells treated
      with MJ or beta-glucan, however, differed with the IB concentration applied. The
      two higher concentrations (50 and 100 mumol/L) of IB significantly reduced the
      betacyanin content while the lower concentration (25 mumol/L) did not show an
      adverse effect on the betacyanin enhancement triggered by MJ or beta-glucan. Our
      findings suggest that, in suspension-cultured cells of Portulaca, an MJ-mediated
      signal transduction pathway prominently exists in betacyanin synthesis. This
      pathway seems to act antagonistically towards beta-glucan-mediated signaling. As
      far as we know this is the first report on the elevation of betacyanin level by
      jasmonate or other elicitors in cell suspension cultures.

PMID- 14593816
TI  - The new ESRD. Demonstration project on disease management.

PMID- 14593815
TI  - Enhancement of transpiration by ethylene is responsible for absence of internodal
      elongation in floating rice at low humidity.
AB  - Internodal elongation in floating rice (Oryza sativa) is known to be enhanced by
      treatment with ethylene or gibberellic acid (GA3) at high relative humidity (RH).
      However, ethylene-induced internodal elongation is inhibited at low RH, while GA3
      induced internodal elongation is hardly affected by humidity. We examined the
      effects of ethylene and GA3 on the rate of transpiration in stem segments
      incubated at 30% or 100% RH. Ethylene promoted the transpiration of stem segments
      at 30% RH, but not at 100% RH, while GA3 had little effect on transpiration at
      either 30% or 100% RH. We propose that the absence of ethylene-induced internodal
      elongation at low RH is due, at least in part, to ethylene-induced transpiration.

PMID- 14593817
TI  - The first ESRD managed care demonstration project: a Kaiser Permanente view.

PMID- 14593818
TI  - Practice guidelines: are they dead on arrival? Yes.

PMID- 14593819
TI  - Practice guidelines: are they dead on arrival? No, but....

PMID- 14593820
TI  - A decade of clinical practice guideline development. Part 1: Rationale.

PMID- 14593821
TI  - Advances in ESRD to be discussed at Renal Research Institute Conference.

PMID- 14593822
TI  - The American Kidney Fund's effort to help minorities with CKD.

PMID- 14593823
TI  - From the trenches: the struggles and triumphs of an urban CKD clinic.

PMID- 14593824
TI  - Psychological assessment in Asia: introduction to the special section.
AB  - Psychological assessment with Asians is an important topic not only for
      psychologists from Asian countries but also for psychologists in multicultural
      societies with large populations of ethnic Asians. There is a dearth of
      information in the English language literature on psychological assessment for
      Asians. This special section is organized to review various forms of
      psychological assessment in Asia. The objectives of the special section are to
      inform test users and researchers of the issues related to cross-cultural
      validity of psychological assessment in Asia and to introduce examples of adapted
      and indigenously developed instruments that are culturally appropriate.

PMID- 14593825
TI  - Use of the MMPI-2 with Asian populations.
AB  - Psychological tests developed in the United States are being widely adapted into
      other languages and cultures around the world. This article examines the
      generalizability and utility of personality assessment instruments across
      cultures and addresses methodological issues related to using personality
      questionnaires in countries different from the one in which they were developed.
      This article specifically highlights the application of objective psychological
      tests in Asia with special emphasis on the most widely used and internationally
      adapted personality instrument, the Minnesota Multiphasic Personality Inventory-
      2 (MMPI-2). Effective strategies for translating, adapting, and standardizing
      questionnaires in languages and cultures different from their country of origin
      are reviewed. The history of several successful adaptations of the original MMPI
      and MMPI-2 is surveyed to illustrate the extensive research base for the test in
      Asia. Current research is summarized, and recommendations for future research are
      provided.

PMID- 14593826
TI  - Recent development of cognitive and neuropsychological assessment in Asian
      countries.
AB  - There is a growing trend of research in neuropsychological assessment in Asia:
      The mean number of published studies increased from 1.8 in the 1980s to 16.0 in 2
      recent years. About 40% of the studies reviewed concerned test development or
      adaptation, with the latter greatly outnumbering the former. To facilitate the
      test selection for clinical use, 36 clinical measures were evaluated based on
      some statistical criteria. The results showed that only 8 neuropsychological
      tests (5 Chinese, 2 Korean, and 1 Japanese) met the criteria. Given that Asian
      and Western populations differ on certain cognitive processes, future development
      of neuropsychological assessment measures in Asia should move from the adaptation
      of Western tests toward the construction of original tests with better ecological
      validity.

PMID- 14593827
TI  - Measures of child and adolescent psychopathology in Asia.
AB  - This article reviews measures of child and adolescent psychopathology used in
      Asian cultures. Sixteen imported measures from the West are identified and their
      psychometric equivalence across cultures is reviewed; 2 new measures are briefly
      introduced. Although initial evidence is generally promising, more studies are
      needed to support their use in Asia. One recently developed Singapore measure
      cannot be considered genuinely indigenous. Culture-specific items proposed for
      imported measures could be grouped into existing diagnostic constructs. There is,
      as yet, no strong theoretical support for culture-bound diagnostic constructs in
      Asian cultures.

PMID- 14593828
TI  - Indigenous measures of personality assessment in Asian countries: a review.
AB  - This article reviews attempts to develop multidimensional personality measures in
      Asia and their applications in clinical assessment. Indigenous personality
      assessment measures in India, Korea, Japan, the Philippines, and Taiwan are
      examined. These early attempts have not yielded a comprehensive personality
      measure that integrates a theoretical framework and an empirical program of
      validation. The Chinese Personality Assessment Inventory (CPAI) is cited as an
      example to illustrate the process of developing an indigenous measure that meets
      the testing standards of established assessment instruments. On the basis of the
      research findings from the CPAI, the authors discuss the relevance of indigenous
      measures in clinical assessment in native cultures as well as in informing
      mainstream personality assessment.

PMID- 14593829
TI  - Assessment of depression and anxiety in East Asia.
AB  - This article provides a critical review of the literature on research with self
      report measures of depression and anxiety in East Asia. Three trends are
      noteworthy. First, research on depression and anxiety in East Asia has relied
      heavily on the use of a limited number of translated instruments. Second,
      available research suggests that the Asian language versions of these instruments
      are reliable and valid for use with Asian populations. Third, some subpopulations
      in East Asia have been studied extensively with respect to depression and
      anxiety, but there are many regions of Asia where little research literature is
      available outside of those published in native language journals. The review
      concludes with recommendations for future research.

PMID- 14593830
TI  - The state of psychological assessment in Asia.
AB  - The collection of articles in this special section provides a much-needed
      examination of the state of psychological assessment in various Asian countries
      or societies. In particular, the contributors review and critique assessment of
      personality, depression and anxiety, children and adolescents, and
      neuropsychological evaluation. The reviews cover the use of, and research on,
      imported measures (Western derived) as well as indigenous measures that were
      developed locally. The articles make a valuable contribution toward understanding
      not only the state of assessment in Asia but also larger issues such as the
      universal applicability of assessment instruments and the cross-cultural validity
      of models of human behavior.

PMID- 14593831
TI  - On the usefulness of measures of normal personality for clinical assessment:
      evidence of the incremental validity of the Revised NEO Personality Inventory.
AB  - As a means of examining the incremental validity of a normal personality measure
      in the prediction of selected Axis I and II diagnoses, 1,342 inpatient substance
      abusers completed the Revised NEO Personality Inventory (NEO-PI-R) and the
      Minnesota Multiphasic Personality Inventory--2 (MMPI-2) and were assessed with
      structured clinical interviews to determine diagnostic status. Results
      demonstrated that scores from the NEO-PI-R (a) were substantially related to the
      majority of diagnoses, accounting for between 8% and 26% of the variance in the
      diagnostic criteria; (b) explained an additional 3% to 8% of the variability
      beyond 28 selected MMPI-2 scale scores; (c) increased diagnostic classification
      an additional 7% to 23% beyond MMPI-2 scale scores; and (d) were significantly
      more useful when examined at the facet trait level than at the domain trait
      level. Implications for incorporating measures of normal personality into
      clinical assessment batteries are discussed.

PMID- 14593832
TI  - The representation of four personality disorders by the schedule for nonadaptive
      and adaptive personality dimensional model of personality.
AB  - This study examined the relationships of the Schedule for Nonadaptive and
      Adaptive Personality (SNAP) model of personality to 4 targeted personality
      disorders (PDs) in a large multisite sample of patients. Data were examined from
      529 patients, who were assigned 1 of 5 primary diagnoses: borderline,
      schizotypal, avoidant, and obsessive-compulsive PDs and major depression without
      PD. Patients were administered the SNAP questionnaire and results were compared
      among diagnostic groups and between patient groups and nonclinical norms. Results
      indicated that the dimensions of the model appear to have considerable promise in
      differentiating normal from abnormal personality, particularly in the propensity
      of individuals with PDs to manifest negative affects and interpersonal
      detachment. Furthermore, the model appeared to successfully distinguish specific
      PDs, a property that represents a particular challenge for dimensional models of
      personality.

PMID- 14593833
TI  - Positive impression management and its influence on the Revised NEO Personality
      Inventory: a comparison of analog and differential prevalence group designs.
AB  - Participants (n = 22) completed the Revised NEO Personality Inventory (NEO PI-R)
      as part of an authentic job application. Protocols produced by this group were
      compared with "analog" participants (n = 23) who completed the NEO PI-R under
      standard instructions and again under instructions designed to mimic the test
      taking scenario of the job applicants (the "fake-good" condition). Participants
      completing the NEO PI-R under fake-good instructions and the job applicants
      scored lower on the Neuroticism and higher on the Extraversion scales than did
      the participants responding under standard instructions. Analog participants in
      the fake-good condition scored higher on the Extraversion and lower on the
      Agreeableness scales than did the job applicants. These results suggest that
      outcomes from analog designs are generalizable to real-world samples where
      response dissimulation is probable.

PMID- 14593835
TI  - Use of the MMPI-2 in American Indians: I. Comparability of the MMPI-2 between two
      tribes and with the MMPI-2 normative group.
AB  - The comparability of the MMPI-2 in American Indians with the MMPI-2 normative
      group was investigated in a sample of 535 Southwestern and 297 Plains American
      Indian tribal members with contrasting sociocultural and historical origins. Both
      American Indian tribal groups had clinically significant higher T scores (> 5 T
      points) on 5 validity and clinical scales, 6 content scales, and 2 supplementary
      scales than did the MMPI-2 normative group. There were no significant differences
      between the 2 tribal groups on any of the MMPI-2 clinical, content, or
      supplementary scales. Matching members of both tribes with persons in the MMPI-2
      normative group on the basis of age, gender, and education reduced the magnitude
      of the differences between the 2 groups on all of these scales, although the
      differences in T scores still exceeded 5 T points. It appears likely that the
      MMPI-2 differences of these 2 American Indian groups from the normative group may
      reflect their adverse historical, social, and economic conditions.

PMID- 14593834
TI  - Factor structure of the psychopathic personality inventory: validity and
      implications for clinical assessment.
AB  - Psychopathy is a personality disorder characterized by impulsive antisocial
      deviance in the context of emotional and interpersonal detachment. A factor
      analysis of the subscales of the Psychopathic Personality Inventory (PPI) yielded
      evidence for 2 factors. One factor showed relations with external criteria
      mirroring those of the emotional-interpersonal facet of psychopathy, including
      high dominance, low anxiety, and venturesomeness. The other factor showed
      relations paralleling those of the social deviance facet of psychopathy,
      including positive correlations with antisocial behavior and substance abuse,
      negative correlations with socioeconomic status and verbal ability, and
      personality characteristics including high negative emotionally and low
      behavioral constraint. Findings support using the PPI to assess these facets of
      psychopathy in community samples and to explore their behavioral correlates and
      genetic-neurobiological underpinnings.

PMID- 14593836
TI  - Use of the MMPI-2 in American Indians: II. Empirical correlates.
AB  - R. W. Robin, R. L. Greene, B. Albaugh, A. Caldwell, and D. Goldman (2003)
      reported that members of 2 American Indian tribal groups had statistically
      significant higher T scores on several MMPI-2 clinical, content, and
      supplementary scales than did the MMPI-2 normative group. The present study
      investigated the empirical correlates of the MMPI-2 scales in these American
      Indian tribal members. There were a large number of significant correlates
      reflecting antisocial symptoms with Scales 4 (Psychopathic Deviate), 9
      (Hypomania), Anger, and Antisocial Practices. There were even a larger number of
      significant correlates reflecting generalized distress and negative affect with
      Scales 7 (Psychosthenia), 8 (Schizophrenia), Anxiety, Obsessions, Depression, and
      Welsh Anxiety. The rationally derived MMPI-2 content scales generally had larger
      correlations with these constructs than the clinical scales. Thus, the
      differences reported by R. W. Robin et al. (2003), appear to reflect behaviors
      and symptoms that American Indians participants were experiencing rather than
      test bias.

PMID- 14593837
TI  - Cross-cultural equivalence and validity of the Vietnamese MMPI-2: assessing
      psychological adjustment of Vietnamese refugees.
AB  - The cross-cultural equivalence and validity of the Vietnamese translation of the
      Minnesota Multiphasic Personality Inventory--2 (MMPI-2) were examined in a sample
      of 1st-generation Vietnamese refugees in the United States (N = 143). Respondents
      completed the Vietnamese MMPI-2, the Harvard Trauma Questionnaire, a measure of
      acculturation, and a demographic questionnaire. An inspection of MMPI-2 mean
      profiles and items showing extreme endorsement rates suggested that certain
      symptom tendencies and cultural values may be reflected in responses to some MMPI
      2 items. Older age, lower acculturation, greater experienced premigration
      postmigration traumas, and military veteran status were all associated with
      elevated MMPI-2 profiles, suggesting that the MMPI-2 functions in a reasonably
      equivalent and valid way in this population.

PMID- 14593838
TI  - Reliability and validity of the Revised Children's Manifest Anxiety Scale in a
      French-Canadian sample.
AB  - The aim of this study was to examine the reliability and validity of a French
      version of the Revised Children's Manifest Anxiety Scale (RCMAS). A sample of
      2,666 school-age French-Canadian children completed the questionnaire. With
      regard to factor structure, the 5-factor model found in U.S. normative samples
      was confirmed. The internal consistency of the 5 scales and of the 2 global
      scales was good to excellent. Test-retest reliabilities after a 6-month period
      were also similar to those of the original version. Finally, the concurrent
      validity, assessed by a correlation with the State-Trait Anxiety Inventory for
      Children, was also found to be good. Results of the present study show that the
      French version of the RCMAS is a good instrument to assess anxiety in children.

PMID- 14593840
TI  - Validity of three measures of communication for predicting relationship
      adjustment and stability among a sample of young couples.
AB  - The goal of this study was to examine whether data from 3 different measures of
      communication (i.e., self-report, quasi-observational, and observational) can
      predict relationship adjustment and stability 1 year later when used conjointly
      in a sample of 62 young couples. The 3 measures of communication were the
      Communication Skills Test--Revised (CST-R), the Communication Box (CB), and the
      Demand/Withdraw Pattern Questionnaire (DWPQ). Through hierarchical multiple
      regression analyses, results revealed that the CST-R and the DWPQ predict both
      genders' relationship adjustment 1 year later when used conjointly. Logistic
      regression analyses revealed that none of the measures of communication
      significantly predicted relationship stability. In conclusion, the combination of
      the CST-R and the DWPQ appears to be useful for longitudinally predicting
      relationship adjustment.

PMID- 14593839
TI  - The Social Thoughts and Beliefs Scale: a new inventory for assessing cognitions
      in social phobia.
AB  - Development and initial psychometric features of a new inventory to assess
      cognitions associated with social phobia are described. The Social Thoughts and
      Beliefs Scale (STABS) is designed to assess cognitions in individuals with social
      phobia. In the 1st study, an initial pool of 45 items was reduced to 21. In the
      2nd study, psychometric features of the scale were examined in a sample of
      individuals with social phobia, other anxiety disorders, and no psychiatric
      disorder. Total scores and two factor scores significantly differentiated
      individuals with social phobia from those in the other groups and were found to
      have adequate test-retest reliability and internal consistency. Potential
      usefulness of the STABS for assessing cognitions associated with social phobia is
      discussed.

PMID- 14593841
TI  - How I feel: a self-report measure of emotional arousal and regulation for
      children.
AB  - This article details the development and preliminary validation of a
      multidimensional self-report measure of emotion for 8- to 12-year-old children-
      the How I Feel (HIF). Item generation and selection occurred via 2 pilot
      administrations (ns = 250 and 378, respectively). Ten experts provided data on
      content validity. Exploratory factor analysis and subsequent confirmatory factor
      analysis with samples of 406, 524, 349, and 349 3rd-through 6th-grade children
      supported a 3-factor model, including the frequency and intensity of (a) positive
      emotion, (b) negative emotion, and (c) positive and negative emotion control.
      Results showed moderate longitudinal stability for 120 children over 2 years.
      Concurrent validity was established. The HIF can be useful in understanding the
      interplay between arousal and control in social-emotional adjustment in school
      age children.

PMID- 14593842
TI  - A multisite comparison of actuarial risk instruments for sex offenders.
AB  - Four actuarial instruments for the prediction of violent and sexual reoffending
      (the Violence Risk Appraisal Guide [VRAG], Sex Offender Risk Appraisal Guide
      [SORAG], Rapid Risk Assessment for Sex Offender Recidivism [RRASOR] and Static
      99) were evaluated in 4 samples of sex offenders (N = 396). Although all 4
      instruments predicted violent (including sexual) recidivism and recidivism known
      to be sexually motivated, areas under the receiver operating characteristic (ROC)
      were consistently higher for the VRAG and the SORAG. The instruments performed
      better when there were fewer missing items and follow-up time was fixed, with an
      ROC area up to .84 for the VRAG, for example, under such favorable conditions.
      Predictive accuracy was higher for child molesters than for rapists, especially
      for the Static-99 and the RRASOR. Consistent with past research, survival
      analyses revealed that those offenders high in both psychopathy and sexual
      deviance were an especially high-risk group.

PMID- 14593843
TI  - Modeling unipolar depression as a chaotic process.
AB  - This study inspected the deterministic structure of unipolar depression. Two
      women self-monitored sadness hourly 10 times a day for 6 months. One woman had a
      recurrent history of unipolar depression, and the other did not. Data were
      analyzed by visual inspection, examination of the Fourier transforms of the time
      plots, and the correlation dimension. Results suggested that in addition to a
      strong periodic component that existed only within the depressed subject's mood
      time series, a low-dimensional chaotic process might have been operating. In the
      nondepressed control subject, no such periodicity or process could be identified.
      The findings support maladaptive deterministic theories of mood disorders and
      have implications for the assessment of unipolar depression.

PMID- 14593845
TI  - "Time out" for patient safety no joke to JCAHO.

PMID- 14593846
TI  - Want help with seniors? Check community agencies.

PMID- 14593844
TI  - Developmental outcome of drug-exposed children through 30 months: a comparison of
      Bayley and Bayley-II.
AB  - This study examined the effects of the Bayley Scales of Infant Development (BSID)
      version on developmental outcomes among drug-exposed children, some of whom
      received an intervention. Developmental outcome was evaluated with the BSID at 12
      and 18 months and with the BSID-II at 24 and 30 months. In the repeated measures
      analyses, children scored higher on the BSID Mental Developmental Index (MDI; p <
      .01) and Psychomotor Developmental Index (PDI; p < .01) than on the BSID-II MDI
      and PDI. Version x Time (p < .01) and Version x Group (p < .01) interactions were
      also found for the MDI but not the PDI. PDI scores decreased on both the BSID and
      the BSID-II (p < .01). Over the first 2 years postpartum, mean MDI and PDI scores
      decreased among these high-risk, drug-exposed children.

PMID- 14593848
TI  - E-prescribing is a tough sell to most doctors.

PMID- 14593847
TI  - Don't let stress make your workplace unhealthy.

PMID- 14593849
TI  - A change of heart: cardiovascular correlates of forgiveness in response to
      interpersonal conflict.
AB  - This study sought to examine the psychophysiological correlates of forgiveness in
      response to interpersonal conflict. One hundred eight college students (44 males
      and 64 females) participated in two interviews about times of interpersonal
      betrayal, one about a parent and one about a friend/partner. Measures of
      forgiving personality and state forgiveness were collected, as well as stress,
      hostility, empathy, and self-reported illness symptoms. During baseline,
      interviews and recovery periods, repeated measures were taken of blood pressure,
      heart rate, frontalis EMG, and skin conductance. Trait forgiveness was associated
      with lower levels of blood pressure. State forgiveness was associated with lower
      blood pressure levels, heart rate, and rate pressure product. Acute, stress
      induced reactivity was also linked to forgiveness: state forgiveness was
      associated with diastolic and mean arterial pressure and rate pressure product
      reactivity during the parent interview. Increased blood pressure recovery after
      stress was also linked to trait forgiveness. Forgiveness may produce beneficial
      effects directly by reducing allostatic load associated with betrayal and
      conflict, and indirectly through reductions in perceived stress.

PMID- 14593851
TI  - Pain self-management in the process and outcome of multidisciplinary treatment of
      chronic pain: evaluation of a stage of change model.
AB  - For chronic pain patients, acceptance of a self-management approach for pain may
      influence success in treatment, and adopting such a perspective may be
      conceptualized as a stage of change model. For 65 chronic pain patients in
      multidisciplinary treatment programs, we examined whether pretreatment self
      management stage, assessed with Pain Stage of Change Questionnaire subscales,
      affected improvements in outcomes, and whether changes in stage represented a
      therapeutic process factor. Results showed (a) low precontemplation, high
      contemplation, and high action attitudes at pretreatment predicted greater
      improvements in outcomes than the opposite pattern of attitudes; (b) pre- to
      midtreatment changes in precontemplation and contemplation attitudes predicted
      mid- to posttreatment changes in pain severity and interference, but not vice
      versa. Results support the usefulness of a stage model in conceptualizing
      patients' acquisition of a self-management approach to pain, and suggest that
      early-treatment progression across stages may lead to reductions in pain severity
      and lifestyle interference.

PMID- 14593850
TI  - Trait anger, anger expression, and ambulatory blood pressure: a meta-analytic
      review.
AB  - A meta-analysis of 15 studies was conducted to investigate the relationship
      between trait anger and ambulatory blood pressure. Overall, the experience of
      anger was significantly and positively associated with systolic blood pressure
      (r+ = 0.049), but not reliably associated with diastolic blood pressure (r+ =
      0.028). After removing an outlier, the expression of anger was found to have a
      reliable inverse relationship with diastolic blood pressure (r+ = -0.072). No
      reliable relationship between expression of anger and systolic blood pressure (r+
      = -0.041) was found. These results continue to support the modest role of self
      reported trait anger and anger expression in blood pressure levels. Several
      suggestions for future research are discussed, including increasing the focus on
      the complexity and synergism of these effects.

PMID- 14593852
TI  - Biological, psychosocial, and sociodemographic variables associated with
      depressive symptoms in persons with type 2 diabetes.
AB  - Studies have found an association between glycemic status and indices of health
      related quality of life in people with diabetes mellitus and comorbid depression.
      No study to date has examined the relative strength of influences of glycemic
      status and health-related quality of life on depression in people with diabetes
      mellitus, nor have important moderators in this relationship been examined. This
      study examined the relative strength of correlations between glycemic status and
      health-related quality of life and depressive symptoms and the degree to which
      those correlations were moderated by sociodemographic variables in 146 people
      with type 2 diabetes. Depressive symptoms were measured with the Centers for
      Epidemiological Studies--Depression (CES-D) scale. Health-related quality of life
      was measured with the SF-36 Health Survey. Hemoglobin A1c (HbA1c) was used as a
      measure of glycemic status and body mass index and waist-hip ratio were measured.
      Results indicated that SF-36 scores accounted for a greater proportion of the
      variance in CES-D scores. The association between CES-D and SF-36 scores was
      moderated by HbA1c, sex, education, marital status, and social support. The
      implications and limitations of these results were discussed in the context of
      past studies.

PMID- 14593853
TI  - Physiological and psychological effects of delivering medical news using a
      simulated physician-patient scenario.
AB  - We examined the acute stress response associated with having to deliver either
      bad or good medical news using a simulated physician-patient scenario. Twenty
      five healthy medical students were randomly assigned to a bad medical news (BN),
      a good medical news (GN), or a control group that read magazines during the
      session. Self-report measures were obtained before and after the task. Blood
      pressure and heart rate were measured throughout the task period. Four blood
      samples were obtained across the task period. The BN and GN tasks produced
      significant increases in self-reported distress and cardiovascular responses
      compared with the control group. There was also a significant increase in natural
      killer cell function 10 min into the task in the BN group compared with the
      control group. The BN task was also somewhat more stressful than the GN task, as
      shown by the self-report and cardiovascular data. These findings suggest that a
      simulated physician-patient scenario produces an acute stress response in the
      "physician," with the delivery of bad medical news more stressful than the
      delivery of good medical news.

PMID- 14593855
TI  - Clinical studies of camptothecin and derivatives.

PMID- 14593856
TI  - Tremorgenic and nontremorgenic 2,3-fused indole diterpenoids.

PMID- 14593854
TI  - Patterns of sexual risk behaviors and psychiatric disorders in a community sample
      of young adults.
AB  - This cross-sectional study documents significant associations between patterns of
      sexual risk behaviors and psychiatric diagnoses in a multiethnic community sample
      of young adults (N = 1803) in South Florida. Self-report data regarding sexual
      behavior and psychiatric symptoms were collected in structured interviews in a
      follow-up of an earlier school-based study. Cluster analysis was used to group
      participants with regard to levels of sexual risk behaviors during the past year.
      Chi-square analysis and ANOVA identified significant associations between cluster
      membership and (a) lifetime and (b) past year diagnoses for affective disorders,
      conduct disorder, antisocial personality disorder, alcohol abuse/dependence,
      marijuana abuse/dependence, and other drug abuse/dependence. In addition, higher
      levels of sexual risk behaviors were associated with higher levels of cumulative
      lifetime psychiatric disorders. Implications for selected prevention of sexually
      transmitted diseases (STDs) and the treatment of psychiatric disorders in young
      adulthood are discussed.

PMID- 14593857
TI  - The Daphniphyllum alkaloids.

PMID- 14593859
TI  - Sesquiterpene pyridine alkaloids.

PMID- 14593860
TI  - Chemical and biological aspects of melanin.

PMID- 14593858
TI  - The manzamine alkaloids.

PMID- 14593861
TI  - [Physiological and biochemical characteristics of immobilized champagne yeasts
      and their participation in sparkling processes].
AB  - Methods for immobilizing champagne yeasts, physiological and biochemical
      characteristics of the immobilized cells, and problems of their utilization in
      the production of quality champagne wines are reviewed. Studies aimed at the
      development of efficient biocatalysts for champaignizing wines using bottle
      fermentation (method champenoise) and tank processing (bulk, or Charmat process),
      based on the use of immobilized yeast cells, are described. Data on the
      industrial use of such biocatalysts in countries manufacturing champagne wines
      are presented. Problems and prospects of further research in this field are
      discussed.

PMID- 14593862
TI  - [Peroxidase refolding in the presence of specific antibodies].
AB  - A panel of eight monoclonal antibodies raised against horseradish root peroxidase
      has been assembled and characterized. Affinity constants were determined for all
      antibodies, and their specificity for various structural forms of the enzyme
      (native peroxidase, apoperoxidase, and denatured peroxidase) were assessed by
      competitive enzyme immunoassay. The effects of the antibodies on the process of
      refolding of peroxidase after its denaturing with 6.5 M guanidine hydrochloride
      were studied spectrophotometrically, by the restoration of the enzymatic activity
      in the reaction of 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonate). The yield
      of the active enzyme in the course of the refolding was increased 1.5 to 1.7
      times in the presence of antibody H1. Effects of the antibodies constituting the
      panel on the activity of native peroxidase and the stability of its dilute
      solutions were analyzed.

PMID- 14593863
TI  - [Effect of industrial toxic pollutants on the activity and isoforms of acid DNase
      in the freshwater snail (Viviparus viviparus L.)].
AB  - The effect of various toxic compounds (phenol, gasoline, detergents, halogenated
      benzenes, and copper salts) on the activity and multiple forms of acid DNase was
      investigated in the liver of the widespread freshwater snail species Viviparus
      viviparus L. Characteristic variations in the specific activity and isoform
      pattern of the enzyme depending on pollutant concentration and exposure time were
      revealed. It was shown that the pattern of DNase isoforms in V. viviparus could
      be an index of water pollution.

PMID- 14593864
TI  - [Effect of endogenous enzymes on composition of oligonucleotides isolated from
      gonads of hydrobionts].
AB  - Preparations of low-molecular-weight DNA were obtained from gonads of various
      hydrobiont species by alcohol precipitation technique. An enzymatic hydrolysis
      based method for producing soluble low-molecular-weight DNA was developed. All
      the nucleic acid components of the preparations obtained were separated by
      electrophoresis, and their molecular weights were determined. It was demonstrated
      that high activities of endogenous enzymes (nucleases and proteases) in milts of
      hydrobionts correlated with the degree of hydrolysis of their nucleic acids.

PMID- 14593865
TI  - [Chitosan depolymerization by enzymes from hepatopancreas of the crab
      Paralithodes camtschaticus].
AB  - An enzyme preparation was isolated from the Paralithodes camtschaticus
      hepatopancreas that exhibited chitinase and chitosanase activities. Treatment of
      chitin and chitosan with this preparation decreased their viscosity-average
      molecular weights by 96 and 41%, respectively. The chromatographic profiles of
      the products of chitin and chitosan hydrolysis suggested that the crab
      hepatopancreas in rich in endochitinases. Enzymatic digestion of chitosan
      increased its solubility and moderately reduced the extent of its acetylation. A
      mathematical approach was proposed for calculating the molecular weights of
      chitosan fractions from weight-average molecular weights determined
      viscometrically.

PMID- 14593866
TI  - [Isolation and characterisation of chitosanase from Bacillus sp. 739 strain].
AB  - The specific nature of the chitosanase activity of the strain Bacillus sp. 739
      has been determined. Maximum enzyme activity was observed in a medium containing
      the biomass of the fruiting bodies of the fungus Macrolepiota procera. The
      chitosanase was purified to homogeneity using chromatography on DEAE-Sephadex A
      50 and Toyopearl HW-50. The molecular weight of the enzyme, assessed by
      electrophoresis (the Laemmli procedure) approximated 46 kDa. Temperature and pH
      optima of the purified chitosanase were in the ranges 45-55 degrees C and 6.0
      6.5, respectively. Time to half-maximum inactivation of the enzyme at 50 degrees
      C was equal to 1 h. With colloidal chitosan as the substrate, the value of K(M)
      of the purified chitosanase was equal to 25 mg/ml. The enzyme also exhibited a
      weak ability to hydrolyze colloidal chitin.

PMID- 14593867
TI  - [O-glycosylhydrolases of marine filamentous fungi. beta-1,3-Glucanases of
      Trichoderma aureviride].
AB  - The ability to produce extracellular O-glycosylhydrolases was studied in 14
      strains of marine filamentous fungi sampled from bottom sediments of the South
      China Sea. The following activities were detected in the culture liquids of the
      fungi: N-acetyl-D-glucosaminidase, D-glucosidase, D-galactosidase, beta-1,3
      glucanase, amylase, and pustulanase. beta-1,3-Glucanases were isolated by
      ultrafiltration, hydrophobic interaction chromatography, and ion-exchange
      chromatography, and their properties were studied. Data on products of enzymatic
      digestion of laminaran, absence of transglycosylation activity, and the pattern
      of action of natural inhibitors confirmed that beta-1,3-glucanase belonged to the
      exo type. Inhibitor analysis demonstrated the role of a thiol group and
      tryptophan and tyrosine residues in the catalytic activity.

PMID- 14593868
TI  - [Comparative stability assessment of laccases from the basidiomycetes Coriolus
      hirsutus and Coriolus zonatus in the presence of effectors].
AB  - Stability characteristics of the laccases of the basidiomycetes Coriolus hirsutus
      and Coriolus zonatus were measured comparatively at temperatures 25 and 40
      degrees C in the presence of various effectors (proteins, salts, polyalcohols,
      polyacids, and polyelectrolytes). Stabilization effects of cations on the
      laccases from C. hirsutus and C. zonatus decreased in the descending series Cu2+
      > Mg2+ > Ca2+ and Ca2+ > Mg2+ > Mn2+, respectively. Tween 20 caused insignificant
      stabilization of the two enzymes. The C. zonatus laccase was also insignificantly
      stabilized as a result of treatment with bovine serum albumin. The enzymatic
      activity of the laccase preparations from C. hirsutus and C. zonatus was
      conserved virtually completely after vacuum drying (84 and 93%, respectively).
      The most effective stabilizer of the C. hirsutus laccase was found to be dextran
      (17 kD). Dry preparations treated with this agent conserved up to 95% of the
      enzymatic activity. The most effective stabilizer of the C. zonatus was
      polyacrylic acid (102% of the initial activity).

PMID- 14593869
TI  - [Effect of wood modification on lignin consumption and synthesis of lignolytic
      enzymes by the fungus Panus (Lentinus) tigrinus].
AB  - Lignin consumption and synthesis of lignolytic enzymes by the fungus Panus
      (Lentinus) tigrinus cultivated on solid phase (modified and unmodified birch and
      pine sawdusts) were studied. The fungus grew better and consumed more readily the
      birch lignin than the pine wood. Peroxidase activity was higher in the case of
      pine sawdust; laccase and lignolytic activities, in the case of birth sawdust.
      Treatment with ammonia or sulfuric acid decreased lignin consumption by the
      fungus cultivated on either medium. Modification of sawdust by ultrasound
      increased lignin consumption and may be recommended for accelerating
      biodegradation of lignocellulose substrates.

PMID- 14593870
TI  - Screening and mutagenesis of Aspergillus niger for the improvement of glucose 6
      phosphate dehydrogenase production.
AB  - The strain of Aspergillus niger ZBY-7 was selected as the original strain of
      glucose 6-phosphate dehydrogenase production. After mutagenesis of the strain
      using UV irradiation and nitrosoguanidine, mutants of Aspergillus niger resistant
      to certain metabolic inhibitor were obtained. Five of the mutants showed
      increased glucose 6-phosphate dehydrogenase production. The mutant resistant to
      antimycin A (Aspergillus niger AM-23) produced the highest level of glucose 6
      phosphate dehydrogenase (695.9% of that from the original strain).

PMID- 14593872
TI  - [A new type of adaptation of the cyanobacterium Spirulina platensis to
      illumination conditions].
AB  - Incubation of cells of the cyanobacterium Spirulina platensis under conditions of
      exposure to low-intensity (2-3 microE m-2 s-1) red light, which was predominantly
      absorbed by photosystem I (PS I), caused atypical adaptation changes. Invariable
      pigment composition and stoichiometry of photosystems was observed in the cells
      incubated under these conditions against the background of a decrease in the rate
      of photosynthetic fixation of CO2 (by one-half) and a 1.5-fold increase in the
      rate of dark respiration relative to cells incubated under conditions of exposure
      to green light. Comparison of these data with a high rate of dark relaxation of
      P700+ in the presence of diuron suggests that deficiency of reduced equivalents
      at the donor side of PS I in the Spirulina cells exposed to red light is
      compensated by electron supply from the respiratory chain NAD(P)H dehydrogenase
      complex.

PMID- 14593871
TI  - [Properties of 2-C-methyl-D-erythritol 2,4-cyclopyrophosphate--an intermediate in
      the non-mevalonate isoprenoid biosynthesis].
AB  - Extraction and purification from the biomass of Corynebacterium ammoniagenes of 2
      C-methyl-D-erhythritol 2,4-cyclopyrophosphate (MEC) was associated with its
      spontaneous transformation into a number of derivatives (which was due to
      pyrophosphate bond lability and the formation of complexes with metals). These
      derivatives included 1,2-cyclophospho-4-phosphate, 2,4-diphosphate, 2,3
      cyclophosphate, 1,4-diphosphate, and 3,5-diphosphate (identified by 1H, 31P, and
      13C NMR spectroscopy) and accounted for about 10% MEC. When added to a solution
      of DNA in the presence of the Fenton reagent, MEC prevented DNA decomposition. In
      addition, MEC slowed down the interaction of the reagent with tempol radicals,
      which indicates that complexation of ferrous ions by MEC attenuates their ability
      to catalyze the formation of hydroxyl radicals from hydrogen peroxide. In the
      presence of 0.23 mM MEC, the rate of respiration of rat liver mitochondria
      increased 1.8 times. At 0.1-1.0 mM, MEC activated in vitro proliferation of human
      Vgamma9 T-cells. It is suggested that MEC acts as an endogenous stabilizing agent
      for bacterial cells subjected to oxidative stress and as an immunomodulator for
      eukaryotic hosts.

PMID- 14593874
TI  - [Oligosaccharide specificity of the fucolectin from the bark of laburnum Laburnum
      anagyroides].
AB  - A comparative study of thin carbohydrate specificity of the lectin from the bark
      of laburnum Laburnum anagyroides (LABA) and fucolectin from asparagus pea
      Tetragonolobus purpureus (TPA) was performed using inhibition of agglutination of
      the complex formed by H-active neoglycoprotein and nanoparticles of colloidal
      gold. Both lectins bound most strongly the H type 2 oligosaccharides comprising O
      glycanes; however, TPA was almost unable to discriminate between them. LABA bound
      more weakly the H type 6 trisaccharide (Fuc alpha 1-2Gal beta 1-4Glc) and
      difucosyllactose (Fuc alpha 1-2Gal beta 1-4[Fuc alpha 1-3]Glc), a glucoanalogue
      of the Le(y) antigen, and, even more weakly, the Le(a) pentasaccharide lacto-N
      fucopentaose II (Gal beta 1-3[Fuc alpha 1-4]GlcNAc beta 1-3Gal beta 1-4Glc).
      However, LABA did not bind the antigens Le(b), Le(c), and Le(d), very poorly
      interacted with the terminal Le(x), and somewhat more strongly bound the internal
      Le(x). The lectin also had a hydrophobic binding site. Both lectins exhibited a
      cluster effect with polymeric ligands (neoglycoproteins).

PMID- 14593873
TI  - [Water-soluble galactomannan from the seeds of Lotus corniculatus L.: structure
      and properties].
AB  - Galactomannan, a water-soluble heteropolysaccharide, was isolated from the seed
      of Far-Eastern population of ground honeysuckle Lotus corniculatus L. (yield,
      1.65%). Analysis of this galactomannan showed that is consists of D-mannose and D
      galactose residues (molar ratio, 1.22:1). Its aqueous solutions were
      characterized by specific rotation [alpha]D = +84.10 and characteristic viscosity
      [eta] = 559 ml/g. Analysis of this heteropolysaccharide using chemical and
      enzymatic procedures, as well as IR- and 13C-NMR spectroscopy, showed that its
      main chain comprises 1,4-beta-D-mannopyranose residues, 95.5% of which are
      substituted at C-6 with single residues of alpha-D-galactopyranose.

PMID- 14593875
TI  - [Preparation of biologically transformed raw material from woolly foxglove
      Digitalis lanata Ehrh and isolation of digoxin from it].
AB  - A biotechnological approach is proposed for conservation of a terraneous part of
      woolly foxglove under anaerobic conditions with a subsequent air-sun drying of
      the biologically transformed raw material. During the conservation primary
      foxglove glycosides completely convert to secondary ones which do not transform
      further. A simple method is described for preparation from the transformed raw
      material of an enriched glycoside fraction with the yield of 3.6% and for
      isolation from this fraction of highly purified digoxin with the yield of 0.06%
      of the starting raw material, and the other secondary glycosides can be also
      isolated.

PMID- 14593877
TI  - [Mineral content in the wild onion species and their nutritive value].
AB  - The accumulation of 11 microelements (Fe, Zn, Cu, Co, Mn, Ni, Pb, Cd, Sr, Cr, and
      Se) by 7 wild onion species of the genus Allium was studied. A. flavescens Bess
      possesses the higher accumulating capability; it accumulates five of eleven
      microelements (Cr, Ni, Cu, Zn, and Se) with biological accumulation coefficient
      (BAC) exceeding 1 and also contains high levels of Fe, Co, and Mn. These features
      enable this species to be the most promising for the nutrition adjustment of
      human commons with above-mentioned microelements primarily with Cr, which content
      in 100 g onion leaves achieves 84% of commons. A. fistulosum L., A. odorum L.,
      and broad-leaved A. nutans form specifically accumulate Cu, Zn, and Se. A.
      montanum Schmidt is characterized by the accumulation of Zn. A. angulosum and A.
      schoenoprasum are xharacterized by the accumulation of Se. The broad-leaved forms
      of A. schoenoprasum L., A. nutans L., and A. odorum L. compared with their narrow
      leaved forms accumulate more amounts of Zn and Cu.

PMID- 14593876
TI  - [Effect of cytokinin preparations on the pools of pigments and proteins of wheat
      cultivars differing in their tolerance to water stress].
AB  - Contents of chlorophylls, carotenoids, soluble leaf proteins, and the key enzyme
      of carbon metabolism--ribulose bisphosphate carboxylase/oxygenase (RuBisCO; EC
      4.1.1.39)--in young seedlings and adult leaves of the wheat Triticum aestivum L.
      cultivars Mironovskaya 808 and Lyutestsens 758, contrasting in their water stress
      tolerances, were compared under conditions of normal available water supply,
      water deficiency, and subsequent rehydration. It was discovered that compounds
      displaying a cytokinin activity (6-benzylaminopurine, thidiazuron, cartolin-2,
      and cartolin-4) reduced the decreases in contents of chlorophylls, carotenoids,
      soluble leaf proteins, and RuBisCO progressing with development of water stress.
      These compounds with cytokinin activity also accelerated restoration of the
      compounds studied to their initial concentrations during rehydration. The
      cartolin preparations caused a maximal protective effect. Water stress had a more
      pronounced negative effect on cultivar Lyutestsens 758. Dehydration resulted in a
      more extensive destruction of seedlings compared to leaves of adult plants.

PMID- 14593878
TI  - Snowmachine related mortality and morbidity in Alaska: a comparison with non
      motorized winter sport.

PMID- 14593879
TI  - Racial differences in birthweight-specific neonatal mortality in Alaska: 1987
      1996.
AB  - OBJECTIVES: This study compared the neonatal mortality in the Alaska Native and
      non-native (primarily white) population in Alaska for a 10-year period (1987
      1996). METHODS: Natality, mortality, and cause of death data were obtained from
      the State of Alaska's Bureau of Vital Statistics (BVS). Birthweight-specific and
      preventable birthweight-specific mortality were analyzed for babies < 1500 grams,
      1500-2499 grams, and > or = 2500 grams birthweight. RESULTS: The low birthweight
      (LBW) and very low birthweight (VLBW) rates were similar for the Alaska Native
      and non-native populations. The neonatal mortality rate for the Alaska Native
      population was higher than for the non-native population (6.4 per 1,000 live
      births for Alaska Native vs. 4.1 for non-native for 1987-1991; 5.5 for Alaska
      Native vs. 3.5 for non-native for 1992-1996). Birthweight-specific mortality was
      higher in the Alaska Native population for all birthweight groups. The exclusion
      of non-preventable conditions accentuated the differences in mortality rates
      between the Alaska Native and non-native population for infants < 2500 grams
      birthweight. CONCLUSION: The higher neonatal mortality in the Alaska Native
      population is associated with a higher overall and preventable birthweight
      specific neonatal mortality. The differences are therefore likely to reflect
      differences in access to and quality of perinatal care.

PMID- 14593880
TI  - Preparedness for a bioterrorism event in Alaska. Part 1: Detection and
      identification of a biologic event.
AB  - U.S. military and public health experts are increasingly concerned that the
      general public is at risk for terrorist attacks. Traditional weapons of mass
      destruction such as explosive and chemical devices remain the most likely forms
      of terrorism, however the threat of bioterrorism is also present and may be
      increasing. An intentional biologic event may be covert and if so, will not
      become apparent for days or even weeks when many ill people present with an
      unidentified illness. Health care providers will be the first responders during a
      biologic attack and will be called upon to diagnose diseases such as anthrax,
      tularemia or even smallpox. In the first of a two-part article, a hypothetical
      scenario is presented to illustrate how such an attack might first be discovered
      and the agent identified. As the scenario unfolds, evidence is collected that
      suggests the outbreak was intentional. Information about epidemiologic clues,
      disease syndromes and specific high-risk agents are discussed.

PMID- 14593881
TI  - [Disclosure and protection of personal information in medical treatments].

PMID- 14593882
TI  - [Recent progress in alcoholic liver diseases].

PMID- 14593884
TI  - [The development of a secondary small bowel volvulus in the course of the
      conservative therapy for the traumatic intramural hematoma of the duodenum and
      jejunum: report of a case].

PMID- 14593883
TI  - [Alcoholic pancreatic injury].

PMID- 14593885
TI  - [Nonalcoholic steatohepatitis due to Crohn disease: a lethal case report].

PMID- 14593886
TI  - [A case of malignant lymphoma of the gallbladder].

PMID- 14593887
TI  - [A case of poorly differentiated mucinous carcinoma of the gallbladder with
      remarkable imaging features].

PMID- 14593888
TI  - [A case of serous cyst adenoma of the pancreas with obstruction of bile duct and
      main pancreatic duct].

PMID- 14593889
TI  - [Case report: habitual alcohol drinking caused early onset of acetaminophen
      induced severe liver damage].

PMID- 14593890
TI  - [Acute and chronic injuries after electrical accidents].
AB  - BACKGROUND: Electrical accidents are potentially fatal incidents with effect on
      the cardiovascular, nerve and musculoskeletal systems and on the skin (burns).
      The electrical engineering industry points out that the follow-up of injured
      persons from site of accident to hospital is quite random. This paper gives a
      review of the current literature and proposes guidelines for the follow-up of
      victims of electrical accidents. MATERIAL AND METHOD: A search of the literature
      was conducted on Medline, Embase, Biosis, Healthline, the Cochrane Library, the
      ISI citation databases, and on several other search engines. The revised
      guidelines were developed in consultation with 23 medical and industry
      institutions. RESULTS AND INTERPRETATION: Serious acute effects of electrical
      accidents include cardiac arrest, respiration failure, burns (also (internal
      burns) with necrosis of e.g. muscle tissue), injuries to the nerve system, and
      renal failure. Traumas caused by falls are also frequent. Possible chronic
      effects are mostly seen in the nerve system as encephalopathy and psychological
      sequelae or as spinal cord and peripheral nerve injury. Most importantly, long
      latent periods are possible for some chronic nerve injuries. This paper suggest
      guidelines for acute (on the spot) action and criteria for referral to hospital,
      observation in hospital and further follow-up.

PMID- 14593891
TI  - [Comparison of the value of disk diffusion methods and polymerase chain reaction
      for fixation of methicillin resistant staphylococcus].
AB  - The detection of methicillin resistance with an appropriate method has a great
      importance in the treatment of infectious diseases caused by staphylococci. This
      study was set out to compare disk diffusion method as a phenotypic method, with
      polymerase chain reaction (PCR), as a genotypic method, for the detection of
      methicillin resistance in staphylococci. A total of 406 staphylococci strains
      that were isolated from clinical specimens in microbiology laboratories of adult
      hospital of Hacettepe University Medical Faculty were included into the study. Of
      406 strains, 248 were identified as Staphylococcus aureus, and 158 were coagulase
      negative staphylococci (CNS). When the disk diffusion test was compared to PCR
      for the detection of methicillin resistance, sensitivity and specificity were
      found as 100% for S. aureus (respectively, 106/106 and 142/142), whereas for CNS
      sensitivity was 100% (86/86) and specificity was 79% (57/72). For CNS, if zone
      diameter for resistance was accepted as < or = 14 mm instead of < or = 17 mm, all
      of the mecA positive strains were found as resistant, whereas three mecA negative
      strains appeared to be resistant by disk diffusion method [sensitivity: 100%
      (86/86), specificity: 95.8% (69/72)]. Although disk diffusion was found as a
      reliable method for the detection of methicillin resistance in S.aureus isolates,
      it couldn't show the same success in CNS. For that reason in order to obtain the
      zone diameter for CNS, further studies are needed.

PMID- 14593892
TI  - [Macrolide resistance phenotypes and genotypes in group G streptococci].
AB  - Group G streptococci (GGS) are among the bacterial causes of pharyngitis. In this
      study, a total of 57 GGS strains isolated from throat swabs were initially
      screened by NCCLS disk diffusion test for penicillin and erythromycin
      susceptibilities. Phenotypes of the erythromycin resistance were determined by a
      triple-disk test and the responsible genes were sought by polymerase chain
      reaction (PCR) using mefA, ermA, ermA-subclass ermTR and ermB primer sets.
      Erythromycin and clindamycin minimal inhibitory concentrations (MIC) of the
      resistant isolates were measured by NCCLS agar dilution method, while
      susceptibility rates to some other antibiotics were determined by the disk
      diffusion test. All isolates were found susceptible to penicillin, and 8 (14%)
      were resistant to erythromycin. Of the resistant isolates, 3 (37.5%) expressed M
      phenotype and 5 (62.5%) had inducible macrolide-lincosamide-streptogramine B
      resistance (iMLS). All M isolates had mefA determinant. Of non-M isolates, 3
      (37.5%) had subclass ermTR. In 2 (25%) isolates none of the four gene
      determinants was detected. MIC ranges of erythromycin and clindamycin for M and
      iMLS phenotypes were 4, 4-128 micrograms/ml and < or = 0.06-0.125, 0.25 - > or =
      128 micrograms/ml, respectively. All the erythromycin-resistant isolates were
      also resistant to tetracycline. The high macrolide-resistance rate of GGS in our
      hospital deserves attention, however this finding should be confirmed by multi
      centre studies including more representative isolates.

PMID- 14593893
TI  - [Mutations of gyrA in ciprofloxacin resistant Escherichia coli strains].
AB  - In this study, the relationship between gyrA mutations and ciprofloxacin minimum
      inhibitory concentration (MIC) values was investigated in Escherichia coli
      strains. For this purpose, ciprofloxacin MIC values of 46 E. coli strains,
      isolated from out-patients and hospitalized patients, were determined by the agar
      dilution method. The "Quinolone Resistance Determining Region" (QRDR) of gyrA
      gene was amplified and restricted by Hinf-I enzyme. Ser-83 mutation was observed
      in all strains that have ciprofloxacin MIC values of 0.062 mg/L and higher.
      Afterwards, eight strains, that were found susceptible (MIC < 1 mg/L, n: 1),
      intermediate (MIC: 1-4 mg/L, n: 1) and high level resistant (MIC > 4 mg/L, n: 6)
      to ciprofloxacin, were chosen and mutations in QRDRs of these strains
      investigated by DNA sequence analysis. Ser 83 Leu mutation was found in all the
      chosen strains and Asp 87 Tyr or Asp 87 Asn mutations were also observed except
      the ciprofloxacin susceptible (MIC: 0.062 mg/L) one. In addition, base
      substitutions that don't lead to aminoacid changes were detected. The strain in
      which only Ser 83 Leu mutation was observed, showed high level nalidixic acid
      resistance (MIC > 256 mg/L). This fact was in favour of that, one mutation is
      enough to develop high level resistance to nalidixic acid. It was concluded that
      high level ciprofloxacin resistance requires at least two mutations in the QRDR
      of gyrA gene.

PMID- 14593894
TI  - [Comparison of auramine-rhodamine and Erlich-Ziehl-Neelsen staining methods for
      the diagnosis of tuberculosis].
AB  - The aim of this study was to compare auramin-rhodamine (A-R) and Erlich-Ziehl
      Neelsen (EZN) staining techniques for the diagnosis of tuberculosis. Of 311
      sputum samples collected from active pulmonary tuberculosis patients and
      tuberculosis-suspected patients, 103 (33%) were found culture positive. In the
      direct microscopic examination of EZN stained smears, 86.4% (89/103) of culture
      positive samples, and 3.8% (8/208) of culture negative samples yielded asido
      resistant bacteria, while these rates were 74.8% (77/103) and 11.5% (24/208) for
      A-R staining method. When culture was accepted as reference method, the
      specificity and sensitivity of the staining techniques were found as 88.5% and
      74.8% for A-R, and 96.2% and 86.4% for EZN, respectively. As a result, it was
      concluded that, the use of A-R staining alone, could not be an alternative method
      to EZN staining.

PMID- 14593895
TI  - [Nasal carriage of Staphylococcus aureus in hospital personnel and the normal
      population and antibiotic resistance of the isolates].
AB  - Nasal carriage of Staphylococcus aureus plays a key role in the epidemiology and
      pathogenesis of infection, and is a major risk factor for the development of both
      community-acquired and nosocomial infections. The objective of this study was to
      investigate the carriage rate of S. aureus in hospital personnel and normal
      population groups, and to compare the resistance rates of the isolated strains to
      certain antibiotics. The nasal carriage rates of S.aureus were found to be 27.5%
      in 262 hospital personnel, and 24.0% in 75 normal healthy subjects (p > 0.05).
      While methicillin resistant S. aureus rate was 9.7% in hospital personnel, no
      methicillin resistant strain was detected in the control group (p < 0.05).
      According to the in-vitro sensitivity test results, resistance rates of
      meticillin sensitive S. aureus (MSSA) strains isolated from hospital personnel to
      fusidic acid, erythromycin and clindamycin were as 11%, 18% and 12%,
      respectively. There were no resistant strains to these antibiotics among MSSA,
      isolated from normal subjects. In conclusion, the colonization of the resistant
      strains rather than the frequency of S. aureus colonization is more important in
      the hospital personnel.

PMID- 14593896
TI  - [Anti-Leptospira antibodies in slaughterhouse workers in Ankara].
AB  - Leptospirosis is one of the zoonotic infections which is widely seen especially
      in tropical regions, and the primary transmission is by direct contact of water,
      contaminated by the secretions of animals. The aim of this study was to
      investigate the seroprevalence of leptospirosis in the slaughterhouse workers,
      who have very close contact with the animals, as a risk factor. The serum samples
      collected from 102 personnel (3 female, 99 male, age range: 19-66 years) who work
      in the different slaughterhouses in Ankara province, have been screened by means
      of anti-leptospira antibodies with a reference method, microscopic agglutination
      test (MAT). In this method, a total of 40 strains were used as antigens,
      including L. interrogans serotype gripptyphosa Moskva V, L. icterohaemorrhagiae
      Wijnberg, L. sejroe Hardjoprajitno, L. pomona Pomona, L. canicola Canicola, L.
      australis Jez-Bratislava and L. biflexa serotype semeranga patoc I. The
      evaluation was made by dark field microscopy, and the presence of agglutination
      in > or = 1/100 titers, were accepted as positive. As a result, in only 2 (1.96%)
      of the sera, anti-leptospira antibodies against L. australis Jez-Bratislava
      antigen were found positive, and it was detected that, these subjects were the
      personnel who worked in the same slaughterhouse for a mean period of 15 years. In
      conclusion, as 100 workers were found seronegative, the seroprevalence of
      leptospirosis is very low in our province.

PMID- 14593897
TI  - [Antibacterial effect of nitric oxide].
AB  - In this study, the antibacterial effects of nitric oxide (NO) have been
      investigated against 4 strains of multidrug-resistant Mycobacterium tuberculosis
      and 8 Klebsiella, 7 Escherichia coli, 7 Staphylococcus, 5 Enterobacter, 7
      Pseudomonas and 7 Proteus clinical isolates by using DETA-NO ((Z)-1-[N-(2
      aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate) as the NO donor.
      Minimum inhibitory concentrations (MICs) were determined by broth microdilution
      method for all tested microorganisms. The MIC values found in our study were as
      follows; 0.25 mg/ml for all of the multidrug-resistant Mycobacterium tuberculosis
      strains, 1 mg/ml for Staphylococcus strains, and approximately 2 mg/ml for the
      rest of the bacterial strains. These results showed that NO (or NO donor DETA-NO)
      was more effective on multidrug-resistant M. tuberculosis strains than the other
      bacterial species. It can be concluded that further studies are needed to explain
      the clinical use of NO donor DETA-NO, especially, in patients infected with
      multidrug-resistant M. tuberculosis.

PMID- 14593898
TI  - [Activity of frequently used disinfectants and antiseptics against nosocomial
      bacterial types].
AB  - In this study, bactericidal activity of widely used disinfectants and antiseptics
      (glutaraldehyde, laurylbispropylidentriamin 5 g and benzalkoniumchlorid 20 g,
      polyvinylpyrolidon iodine, benzalkonium chloride and sodium hypochloride) against
      some nosocomial bacterial isolates were investigated by qualitative and
      quantitative suspension test methods. One methicillin-resistant Staphylococcus
      aureus (MRSA), 6 multi drug-resistant Gram-negative hospital isolates
      (Escherichia coli, Pseudomonas aeruginosa, Enterobacter cloaca, Klebsiella
      pneumoniae, Citrobacter diversus, Serratia marcescens) and 3 standard strains of
      American Type Culture Collection (ATCC) bacteria (S. aureus, P. aeruginosa, E.
      coli) were tested against three different concentrations of disinfectants of
      which, manufacturer's recommended use-dilution, 1/2 and 1/4 of those recommended
      dilutions. All tested disinfectants were found effective in all three
      concentrations against nosocomial isolates in five minutes, by using both
      qualitative and quantitative suspension methods. When the test was repeated with
      albumine, bactericidal activities of disinfectants were found the same. Our
      findings showed that these disinfectants can be still used in safe for the
      sterilization in hospital, and routine disinfection protocols do not need to be
      alerted.

PMID- 14593899
TI  - [Cyclic citrullinated peptide antibodies (anti-CCP) together with some other
      parameters used for serologic diagnosis of rheumatoid arthritis].
AB  - Rheumatoid arthritis (RA) is one of the most common rheumatic disease, which is
      primarily diagnosed by clinical history, physical examination, and laboratory
      tests, including a large number of biochemical and biologic markers. Recently, it
      has been shown that the amino acid citrulline, which is a unit of filaggrin, is a
      substantial component of the antigenic epitope, and enzyme immunoassays which use
      synthetic citrullinated peptide are highly effective tests for the detection of
      autoantibodies against cyclic citrullinated peptide (CCP), which are a new a
      highly specific marker for RA. The aim of this study was to investigate the
      presence of anti-CCP antibodies in RA suspected patients and to evaluate the
      combination of these autoantibodies with some other serologic markers such as IgM
      rheumatoid factor (IgM-RF), C-reactive protein (CRP) and antinuclear antibodies
      (ANAs). For this purpose, the concentrations of RF and CRP were determined by
      quantitative immunonephelometry, titres of ANAs by indirect immunofluorescence,
      and presence of anti-CCP by a commercial semiquantitative microELISA method, in
      88 patients with clinically suspected RA, as well as 42 sex- and age-matched
      healthy blood donors. As a result, the high levels of IgM-RF and CRP were found
      in 48 (54.5%) and 49 (55.7%) of the patients, respectively, while 47 (53.4%) and
      25(28.4%) patients were found positive for ANAs and anti-CCP, respectively. Of 48
      RF positive patients, 25 were also positive for anti-CCP, and the distribution
      rates of the markers in 25 anti-CCP positive patients were as follows; 100% for
      RF, 84% for CRP and 52% for ANA. The sensitivity of anti-CCP ELISA was 52.1% and
      specificity was 100%, when evaluated according to RF positivity as a main
      serologic marker of RA. In conclusion, anti-CCP antibody testing may be useful in
      the serologic diagnosis of RA patients, especially in combination with RF,
      however more detailed follow-up clinical studies on the large number of patients
      with established RA, would be needed for our country.

PMID- 14593900
TI  - [Comparison of the methods used for the detection of antinuclear antibodies].
AB  - The production of one or more autoantibodies in the majority of rheumatic
      diseases is a common clinical finding. Indirect immunofluorescent antibody (IFA)
      test is the former and widely used method in detecting autoantibodies. Recently,
      commercial enzyme immunoassays (EIA) and immunoblot (IB) assays are available for
      the routine laboratories. The aim of this study was to compare the efficacies of
      these methods in 121 sera samples which were collected from 46 male and 75 female
      patients, of whom antinuclear antibody (ANA) testing were requested by
      clinicians. All the samples were simultaneously studied by IFA with HEp-2 and
      Crithidia lucillae cells, and by two different commercial kits of EIA and IB, and
      the results were evaluated. When IFA is accepted as reference method, the
      sensitivities and specificities of the other methods were found as follows,
      respectively; 82-100% and 84-100% for ANA-EIA, 48-54% and 98-100% for ANA-IB, 66
      100% and 97-98% for anti-dsDNA-EIA, and 50-66% and 86-100% for anti-dsDNA-IB. The
      agreement rates of ANA-EIA, ANA-IB, anti-dsDNA-EIA and anti-dsDNA-IB methods with
      IFA were detected as 82-90%, 74%, 96-97%, and 84-98%, respectively. As a result,
      it may be concluded that IFA test should be used as a primarily test for the
      detection of ANA and anti-dsDNA autoantibodies, while EIA and IB methods are
      useful for antigen differentiation and confirmation of the results.

PMID- 14593901
TI  - [Human herpesvirus 6 infections in kidney and bone marrow/stem cell transplant
      recipients].
AB  - In this study, active human herpesvirus (HHV)-6 infection were investigated in 39
      renal and 9 bone marrow/stem cell transplant recipients. For this purpose, the
      presence of HHV-6 DNA in patients sera have been searched by nested polymerase
      chain reaction (nPCR). In addition, HHV-6 IgM and IgG antibodies were performed
      by micro-enzyme immunoassay (EIA) to detect seronegative patients before
      transplantation and IgM response in active or primary HHV-6 infection. Active
      infection with HHV-6 DNA positivity was detected in 5.3% of renal and 22.2% of
      bone marrow/stem cell transplant recipients. Active HHV-6 infection was found to
      be related with asymptomatic reactivation, graft disfunction and cytomegalovirus
      disease in renal transplant recipients, and, fever and graft versus host disease
      in bone marrow/stem cell transplant recipients. It has been concluded that, the
      investigation of HHV-6 DNA by nPCR in the transplant sera, was a practical and
      useful method for the laboratories, in order to diagnose active HHV-6 infection,
      while HHV-6 IgG antibody detection was also useful for the differential diagnosis
      of primary infection or reactivation/reinfection, but HHV-6 IgM antibodies has
      low value to detect active HHV-6 infection.

PMID- 14593902
TI  - [Prevalence of extrahepatic illnesses in patients with chronic hepatitis b and
      hepatitis c: retrospective study of 435 patients].
AB  - Chronic infections that caused by hepatitis B and C viruses, are important all of
      the world as a public health problem. Despite intensive control measurements, the
      incidences of chronic hepatitis B and C virus infections in our country are
      estimated as 5-7% and 3%, respectively. There are accumulating data of especially
      autoimmune mediated extrahepatic manifestations of hepatitis B and C virus
      infections, such as Diabetes Mellitus (DM), Behcet's Disease (BD), hypo- or hyper
      thyroiditis and autoimmune diseases. The aim of this study was the retrospective
      evaluation of 400 chronic B hepatitis (CBH) and 35 C hepatitis (CCH) patients by
      means of the presence of extrahepatic manifestations. As a result, the positivity
      rates of extrahepatic manifestations detected in CBH and CCH patients were as
      follows respectively; 1.5% and 8.5% for DM, 1.5% and 5.7% for hypothyroiditis,
      0.75% and 2.8% for hyperthyroiditis, 2% and 20% for nodular goitre, 0.25% and
      5.7% for BD, 1% and 0% for systemic lupus, 1% and 5.7% for Rheumatoid Arthritis
      (RA), and 22% and 11.4% for iron deficiency anemia. DM, thyroid diseases and RA
      were the most common extrahepatic manifestations detected in both of the patient
      groups, while the rates of DM, BD and nodular goitre were found higher in CCH
      patients than CBH patients (p < 0.05). As a result, the extrahepatic
      manifestations should be carefully followed in patients with chronic hepatitis B
      and C infections, for an early diagnosis and appropriate treatment.

PMID- 14593903
TI  - [Current approaches to the clinical virologic diagnosis of viral respiratory
      tract infections].
AB  - Respiratory viruses (respiratory syncytial virus, influenza virus type A and B,
      parainfluenza virus and adenovirus) can cause a wide variety of human disease.
      Viral respiratory diseases in adults and children cause significant morbidity and
      mortality. Proper and rapid diagnosis of these etiological agents is necessary
      for the appropriate use of effective antiviral drugs and to decrease unnecessary
      antibiotic therapy. Many virology laboratories detect respiratory viruses by
      inoculating conventional cell culture tubes with respiratory samples and then
      examining for cytopathic effect or hemadsorption. However, this procedure can
      require many days or even weeks for viral detection and identification, providing
      culture results to clinicians in a period of time that may not be clinically
      useful. Laboratory diagnosis of respiratory virus infections has become easier
      and more rapid with the use of immunofluorescent antibody tests, shell vial
      culture methods, and molecular biological assays. In this review article, the
      specificities and sensitivities of these assays were compared on the basis of
      recent studies, and the favorable ones for the routine diagnosis were updated.

PMID- 14593904
TI  - [Genital herpes infections].
AB  - Genital infections caused by herpes simplex viruses (HSV), are the most
      frequently seen sexually transmitted diseases (STD), in both developed and
      developing countries like our country. These infections take part of the third
      important place among STD after from the chlamydial cervicitis and genital wards,
      and are of the major public health problem, recently. Genital herpes infections
      produced mainly (90%) by HSV type 2, and rarely (10%) by HSV type 1. The
      infections may have seen in two clinical forms, called primary and recurrent
      infections. The data have indicated that, the incidence of genital herpes
      increased approximately 20 folds in the world during the last two decades. The
      main factor attributed to the spread of HSV infections includes asymptomatic
      virus shedding. Genital herpes is associated with significant morbidity and
      complications such as neonatal herpes, results from the transmission of HSV from
      mother to fetus. In this review article, the clinical characteristics,
      epidemiology, diagnostic methods, prevention and therapy choices of HSV genital
      infections, have been discussed under the light of recent literature.

PMID- 14593905
TI  - [Medical importance of yeast killer toxin].
AB  - Yeast killer toxins (YKT) are exotoxins produced by several yeasts including
      certain Candida species. They can kill fungi, bacteria and even protozoa by
      binding to the specific receptors on their cell surfaces. On the basis of their
      killer effect, studies have been carried out on the differentiation of fungi and
      some bacteria by using YKT as epidemiological tools. Following biotyping
      procedures, idiotypic and anti-idiotypic antibodies produced against YKT have
      been shown to exhibit great potential in protection and immunotherapy against
      several microorganisms, promising as novel approaches to fight against microbial
      diseases. In this review article, the structural properties, ecologic and
      epidemiologic importance, therapeutic, prophylactic and immunotherapy studies of
      yeast killer toxins, have been discussed.

PMID- 14593907
TI  - Health plan achieves success despite falling cap rates.

PMID- 14593906
TI  - [Hepatitis A virus and coronary artery disease: serologic relationship absent].

PMID- 14593908
TI  - NY Medicaid managed care plans show slower growth in 2003.

PMID- 14593909
TI  - Study documents a changing managed care marketplace.

PMID- 14593910
TI  - Study shows UR in action in two capitated medical groups.

PMID- 14593911
TI  - Uneven growth in physician comp continues, surveys find.

PMID- 14593912
TI  - [Oct-1 transcription factor--plasticity and polyfunctionality].
AB  - The problem considered is how one transcription factor controls numerous
      processes in the organism. The mechanisms determining the multiplicity of Oct-1
      functions are described.

PMID- 14593913
TI  - [Plastidic genome of higher plants and algae: structure and function].
AB  - The data on the structure and gene content in completely sequenced plastid
      (predominantly chloroplast) genomes of higher plants and algae are reviewed. In
      higher plants, genome structure and gene content are highly conserved. Plastid
      genomes of algae are less conserved and contain several unique genes, which are
      not found in chloroplast DNAs of higher plants. Plastid genomes encode proteins
      involved in transcription and translation, as well as proteins of the
      photosynthetic apparatus and photosynthetic metabolism. The problems of origin
      and evolution of plastids are briefly discussed. The data published by the first
      half of 2002 are presented. Use was made of databases OGMP
      (http://megasun.bch.umontreal.ca/ogmp/projects/other/cp_list.html) and NCBI
      (www.ncbi.nlm.nih.gov).

PMID- 14593914
TI  - [Role of polymorphic variants of cytochrome P450 genes (CYP1A1, CYP2E1) and
      microsomal epoxide hydrolase (mEPHX) in pathogenesis of cystic fibrosis and
      chronic respiratory tract diseases].
AB  - Frequencies of CYP1A1, CYP2E1, and mEPHX polymorphic variants were analyzed in
      cystic fibrosis, chronic obstructive lung disease, bronchiectatic disease,
      chronic nonobstructive bronchitis, and recurring bronchitis. Mutations in CYP1A1
      and mEPHX were shown to modify the severity of respiratory disorders in cystic
      fibrosis, the combination of CYP1A1 genotype Val/Val with the "very slow" mEPHX
      phenotype being most unfavorable (odds ratio OR = 12.30). Heterozygosity at both
      CYP1A1 and CYP2E1 was associated with chronic obstructive lung disease and
      recurring bronchitis (OR = 4.08 and 11.72, respectively). The "very slow"
      phenotype of mEPHX was predisposing to chronic respiratory disorders regardless
      of the CYP1A1 or CYP2E1 alleles (OR = 4.06). Basing on the above correlations, a
      combination of the "very slow" mEPHX phenotype with elevated cytochrome P450
      (CYP1A1 and CYP2E1) activities was assumed to expedite severe respiratory
      disorders.

PMID- 14593915
TI  - [Detection of the DeltaF508 trinucleotide deletion in the human CFTR gene by UV
      immobilization on nylon of a complex of a PCR fragment with a highly specific
      probe].
AB  - Deletion delta F508 has been revealed in PCR-amplified regions of human gene CFTR
      by color detection of the hybridization complex obtained by ligation of a tandem
      of short oligonucleotides on a DNA template followed by UV immobilization on
      nylon. The method allows reliable detection of the three-nucleotide deletion
      (insertion). The nonspecific signal depends on the nucleotide composition of the
      biotinylated tandem component. A significant level of the specific signal was
      achieved by using the PCR-amplified DNA fragments of different length (200-400
      bp) irrespective of the position of the tandem-binding site in their sequences.

PMID- 14593916
TI  - [Thermotoga neapolitana gene clusters participating in degradation of starch and
      maltodextins: molecular structure of the locus].
AB  - A 5451-bp genome fragment of the hyperthermophilic anaerobic eubacterium
      Thermotoga neapolitana has been cloned and sequenced. The fragment contains one
      truncated and three complete open reading frames highly homologous to the
      starch/maltodextrin utilization gene cluster from Thermotoga maritima whose
      genome sequence is known. The incomplete product of the first frame is highly
      homologous to MalG, the E. coli protein of starch and maltodextrin transport. The
      product of the second frame, AglB, is highly homologous to cyclomaltodextrinase
      with the alpha-glucosidase activity TMG belonging to family 13 of glycosyl
      hydrolases (GH13). The product of the third frame, AglA, is homologous to the
      Thermotoga maritima cofactor-dependent alpha-glucosidase from the GH4 family. The
      two enzymes form a separate branch on the phylogenetic tree of the family. The
      AglA and AglB proteins supplement each other in substrate specificity and can
      ensure complete hydrolysis to glucose of cyclic and linear maltodextrins, the
      intermediate products of starch degradation. The product of the fourth reading
      frame has sequence similarity with the riboflavin-specific deaminase RibD from T.
      maritima. The homologous locus of this bacterium, between the aglA and ribD
      genes, has five open reading frames missing in T. neapolitana. The nucleotide
      sequences of two frames are homologous to transposase genes. The deletion size is
      2.9 kb.

PMID- 14593918
TI  - [Creation of a convenient vector for transformation of Drosophila with functional
      FRT-pFRT sites].
AB  - Modification of Drosophila transformation vector pCaSper3 with the P element was
      used to construct a new vector, pFRT. The vector contains two tandem FRT sites
      flanked with several unique restriction sites and separated by a polylinker of
      five restriction sites, and allows easy cloning of DNA fragments between or close
      to the FRT sites. FRT-mediated excision of DNA sequences cloned between the FRT
      sites was demonstrated in vivo. The vector was proposed for molecular genetic
      studies of the position effect variegation, structural and molecular organization
      of Drosophila polytene chromosomes, etc.

PMID- 14593917
TI  - [Thermotoga neopolitina gene cluster, participating in degradation of starch and
      maltodextrins: expression of aglB and aglA gene in Escherichia coli, properties
      of recombinant enzymes].
AB  - The aglB and aglA genes from the starch/maltodextrin utilization gene cluster of
      Thermotoga neapolitana were subcloned into pQE vectors for expression in
      Escherichia coli. The recombinant proteins AglB and AglA were purified to
      homogeneity and characterized. Both enzymes are hyperthermostable, the highest
      activity was observed at 85 degrees C. AglB is an oligomer of identical 55-kDa
      subunits capable of aggregation. This protein hydrolyses cyclodextrins and linear
      maltodextrins to glucose and maltose by liberating glucose from the reducing end
      of the molecules, and it is a cyclodextrinase with alpha-glucosidase activity.
      The pseudo-tetrasaccharide acarbose, a potent alpha-amylase and alpha-glucosidase
      inhibitor, does not inhibit AglB but, on the contrary, acarbose is degraded
      quantitatively by AglB. Recombinant AglB is activated in the presence of CaCl2,
      KCl, and EDTA, as well as after heating of the enzyme. AglA is a dimer of two
      identical 54-kDa subunits, and it hydrolyses the alpha-glycoside bonds of
      disaccharides and short maltooligosaccharides, acting on the substrate from the
      non-reducing end of the chain. It is a cofactor-dependent alpha-glucosidase with
      a wide action range, hydrolysing both oligoglucosides and galactosides with alpha
      link. Thereby, the enzyme is not specific with respect to the configuration at
      the C4 position of its substrate. For the enzyme to be active, the presence of
      NAD+, DTT, and Mn2+ is required. Enzymes AglB and AglA supplement one another in
      substrate specificity and ensure complete hydrolysis to glucose for the
      intermediate products of starch degradation.

PMID- 14593919
TI  - [Molecular analysis of alpha-galactosidase MEL genes from Saccharomyces sensu
      stricto].
AB  - To infer the molecular evolution of yeast Saccharomyces sensu stricto from
      analysis of the alpha-galactosidase MEL gene family, two new genes were cloned
      and sequenced from S. bayanus var. bayanus and S. pastorianus. Nucleotide
      sequence homology of the MEL genes of S. bayanus var. bayanus (MELb), S.
      pastorianus (MELpt), S. bayanus var. uvarum (MELu), and S. carlsbergensis (MELx)
      was rather high (94.1-99.3%), comparable with interspecific homology (94.8-100%)
      of S. cerevisiae MEL1-MEL11. Homology of the MEL genes of sibling species S.
      cerevisiae (MEL1), S. bayanus (MELb), S. paradoxus (MELp), and S. mikatae (MELj)
      was 76.2-81.7%, suggesting certain species specificity. On this evidence, the
      alpha-galactosidase gene of hybrid yeast S. pastorianus (S. carlsbergensis) was
      assumed to originate from S. bayanus rather than from S. cerevisiae.

PMID- 14593920
TI  - [Search for alternative secondary structures of RNA, regulating expression of
      bacterial genes].
AB  - Expression of many bacterial genes is regulated by formation of alternative
      secondary RNA structure within the leader mRNA sequence. Our algorithm designed
      to search for these structures (basing on analysis of one nucleotide sequence)
      was applied to analyze operons of amino acid biosynthesis in alpha- and gamma
      proteobacteria. The attenuators of these operons are predicted for genomes of
      some poorly known gamma-proteobacteria including Shewanella putrefaciens,
      attenuators of the tryptophan operon in some alpha-proteobacteria are also
      predicted.

PMID- 14593921
TI  - [Computer analysis of regulating metabolism of glycerol-3-phosphate in
      proteobacteria genome].
AB  - Comparative computer-assisted analysis was used to study putative GlpR-regulons
      responsible for metabolism of glycerol and glycerol-3-phosphate in genomes of
      alpha-, beta-, and gamma-proteobacteria. New palindromic GlpR-binding signals
      were identified in gamma-proteobacteria; consensus sequences being
      TGTTCGATAACGAACA for Enterobacteriaceae, wTTTTCGTATACGAAAAw for Pseudomonadaceae,
      and AATGCTCGATCGAGCATT for Vibrionaceae. The signals in alpha- and beta
      proteobacteria were also identified: they contained 3-4 direct TTTCGTT repeats
      separated by 3-4 nucleotide pairs.

PMID- 14593922
TI  - [Search for conservative secondary structures of RNA].
AB  - We suggest a new algorithm to search a given set of the RNA sequences for
      conserved secondary structures. The algorithm is based on alignment of the
      sequences for potential helical strands. This procedure can be used to search for
      new structured RNAs and new regulatory elements. It is efficient for the genome
      scale analysis. The results of various tests run with this algorithm are shown.

PMID- 14593923
TI  - [Determination of glycyrrhizic acid binding sites by a phage display method].
AB  - Phages that expose peptides specifically interacting with glycyrrhizic acid (GA)
      were selected from a phage peptide library by affinity selection and ELISA. Amino
      acid sequence analysis of the selected peptides and human proteins with the SIM
      program revealed homology to tyrosine protein kinases, serine/threonine protein
      kinases, tyrosine phosphatases, and some receptors. Analysis of the peptide and
      virus protein sequences with the BLAST program showed that GA has affinity for
      various surface proteins of several human viruses such as HIV-1, hepatitis C
      virus, and herpesviruses.

PMID- 14593925
TI  - [Viral promoter-enhancer element inhibits replication of autonomously replicating
      plasmid in mammalian cells].
AB  - To study the autonomous replication of constructs combining replication and
      transcription elements, hybrid plasmids were designed to contain both higher
      eukaryotic ori/ARS and the cytomegalovirus (CMV) promoter-enhancer. In pCI.ARS
      neo, ARS was from autonomously replicating stable transgene pr8a of silkworm
      Bombyx mori. In pCI.ori-neo, chromosomal ori was from the human c-myc locus.
      Analysis of the maintenance of pCI.ARS-neo and pCI.ori-neo in transgenic mice and
      in cultured immortalized human T cells revealed the interplay of transcription
      and replication, as the CMV element suppressed autonomous replication of both
      plasmids. This might reflect the conflict between transcription and replication
      of the genome in higher eukaryotic cells.

PMID- 14593924
TI  - [Variants of adenovirus type 5 with deletions in early genes: ability for
      selective replication in p53-defective human tumor cells].
AB  - Site-directed mutagenesis was used to construct human adenovirus serotype 5 (Ad5)
      variants defective in E1A or E1B. Mutant Adel3 with deletion from E1A was
      markedly attenuated in permissive cell cultures regardless of the p53 status, and
      replicated efficiently only in cells of the complementing 293 line. Mutant Adel2
      with deletion from E1B55K infected the 293 line cells and p53-deficient human
      tumor cells (A431, SW480, HEp2) with efficiencies similar to those of Ad5,
      whereas its replication in normal p53-positive cells was substantially limited.
      Thus, Adel2 proved to be capable of selective infection and lysis of p53
      deficient human tumor cells in vitro. On intratumor injection, Adel2 dramatically
      suppressed the growth of human epidermoid carcinoma (A431) in nude mice. Adel2 is
      thus a promising model for designing therapeutic agents against p53-deficient
      human tumors.

PMID- 14593926
TI  - [Inactivation of pgsA gene affects biosynthesis and secretion of Escherichia coli
      alkaline phosphatase].
AB  - Inactivation of pgsA, which is responsible for biosynthesis of anionic
      phospholipid phosphatidylglycerol (PG), was shown to affect biosynthesis and
      secretion of alkaline phosphatase (PhoA) in Escherichia coli. A decrease in PG,
      but not in total anionic phospholipids, correlated with reduction of PhoA
      secretion, suggesting the role of PG in this process. A dramatic decrease in PG
      (from 18 to 3, but not 8, percent of the total phospholipids) inhibited not only
      secretion, but also synthesis of PhoA. In addition, pgsA inactivation expedited
      repression of PhoA synthesis by exogenous orthophosphate.

PMID- 14593927
TI  - [Interaction of Escherichia coli RNA polymerase with eukaryotic TATA-binding
      protein].
AB  - Interaction with eukaryotic TATA-binding protein (TBP) was analyzed for natural
      Escherichia coli RNA polymerase or the recombinant holoenzyme, minimal enzyme, or
      its sigma subunit. Upon preincubation of full-sized RNA polymerase with TBP and
      further incubation with a constant amount of 32P-labeled phosphamide derivative
      of a TATA-containing oligodeoxyribonucleotide, the yield of the holoenzyme
      oligonucleotide covalent complex decreased with increasing TBP concentration.
      This was considered as indirect evidence for complexing of RNA polymerase with
      TBP. In gel retardation assays, the holoenzyme, but neither minimal enzyme nor
      the sigma subunit, interacted with TPB, since the labeled probe formed complexes
      with both proteins in the reaction mixture combining TBP with the minimal enzyme
      or the sigma subunit. It was assumed that E. coli RNA polymerase is functionally
      similar to eukaryotic RNA polymerase II, and that the complete ensemble of all
      subunits is essential for the specific function of the holoenzyme.

PMID- 14593928
TI  - [Interaction of human S26 ribosomal protein with fragments of mRNA and pre-mRNA
      for this protein in Hela nuclear cell extracts].
AB  - As shown by nitrocellulose filtration assays with RNA fragments transcribed from
      various regions of the human ribosomal protein (rp) S26 gene, recombinant rpS26
      binds to the first intron of the rpS26 pre-mRNA (apparent association constant
      (Ka) approximately 5.0 x 10(7) M-1) and, to a lesser extent, to the rpS26 mRNA
      (Ka approximately 2.0 x 10(7) M-1). The binding was specific, since human rpS19
      had an order of magnitude lower Ka with the first intron and did not bind with
      the rpS26 mRNA. Immunoassays with specific antibodies showed that rpS26 contained
      in the nuclear extract of HeLa cells binds to the first intron of its pre-mRNA
      and, less efficiently, to its mRNA. In either case, RNA binding substantially
      increased in the presence of recombinant rpS26. Along with other (48 K, 59 K)
      nuclear proteins, rpS26 was assumed to form complexes, the functional role of
      which is storage of pre-mRNAs inactive in splicing.

PMID- 14593929
TI  - [Covalent binding of Cys142 from SsoII methyltransferase with DNA duplexes,
      containing a phosphoryldisulfide internucleotide group].
AB  - DNA duplexes containing a single phosphoryldisulfide link in place of the natural
      internucleotide phosphodiester bond were employed in affinity modification of
      Cys142 in cytosine-C5 DNA methyltransferase SsoII (M.SsoII). The possibility of
      duplex-M.SsoII conjugation as a result of disulfide exchange was demonstrated.
      The crosslinking efficiency proved to depend on the DNA primary structure,
      modification position, and the presence of S-adenosyl-L-homocysteine, a
      nonreactive analog of the methylation cofactor. The SH group of M.SsoII Cys142
      was assumed to be close to the DNA sugar-phosphate backbone in the DNA-enzyme
      complex.

PMID- 14593930
TI  - [Biosynthesis of mini-antibodies to human ferritin in plant and bacterial
      producers].
AB  - A recombinant scFv antibody against human spleen ferritin was expressed as a
      barstar-fused protein in Escherichia coli and in Nicotiana tabacum plants and
      suspension cell cultures. As demonstrated by immunoblotting with antibarstar
      antibodies, direction of the recombinant protein to the endomembrane system of
      plant cells ensured its stability and solubility. Production of the recombinant
      protein did not differ between parental transgenic plants and their first
      generation progeny. Fusion with barstar allowed not only immunochemical detection
      of the recombinant scFv antibody, but also their purification from the plant
      material by affinity chromatography with barnase-His6 immobilized on a metal
      affinity carrier.

PMID- 14593931
TI  - [Septic arthritis of the shoulder and hip joint in cattle: diagnosis and
      therapy].
AB  - During eight years, in 17 cattle a septic arthritis of the shoulder or hip joint
      was diagnosed at the Veterinary Surgery Department, University of Munich. The
      diagnosis was based on the results of the synoviocentesis and confirmed by
      ultrasound and radiographic examination. The average number of leucocytes in the
      synovia was 65,137/microliter (median 43.344/microliter), with 97% neutrophils
      (median 96%). Of the 17 animals, 13 were treated. In two patients arthrotomy, and
      in 11 repeated joint lavage was performed. As a lavage solution, 500 to 1000 ml
      of Ringer's solution, with 800 to 1600 mg Gentamicin added, was used. Four
      animals were not treated because of advanced radiographic changes (1), purulent
      arthritis and phlegmon (1) or economic reasons (2). Ten patients could be cured
      long-term (follow up time 10.5 months on average, median 6.5 months), three
      remained lame and were slaughtered. As a conclusion, septic arthritis of the
      shoulder or the hip joint in cattle has a good prognosis when diagnosed and
      treated early.

PMID- 14593933
TI  - [PKD: the proliferative kidney disease in fish].
AB  - The present study gives an overview about the knowledge and the diagnostic
      possibilities of the proliferative kidney disease (PKD) in fishes. This disease
      is responsible for economically significant losses in farmed fish and severe
      reductions in wild fish populations in Europe and North America. PKD is affecting
      mainly salmonid species. In Swiss rivers the proliferative kidney disease
      pictures the highest percentage of diseases among brown trouts. The main symptom
      of PKD is a massive proliferation of the interstitial kidney tissue which named
      the disease. Other unspecific symptoms are anemia, ascites, exophthalmus and
      apathy. The causative agent of the disease is Tetracapsula bryosalmonae
      (Myxozoa). Many aspects of the life cycle of this parasite remain unclear so far
      but it is known that the appearance of this parasite is linked to the presence of
      a range of freshwater bryozoans. PKD appears mostly in summer during high water
      temperatures (> or = 15 degrees C) and can lead to high mortality rates. A
      diagnosis can be made by using light-microscopic, lectinimmunhistochemical as
      well as molecular biological methods. Before we can develop successful management
      strategies the knowledge gaps in understanding the disease cycle and the exact
      pathogenesis of PKD need to be closed.

PMID- 14593932
TI  - Retrospective study on the presence and pathogenicity of Dirofilaria repens in 5
      dogs and 1 cat from Aosta Vally.
AB  - Aosta Valley is the only region of Italy free of reported human cases of
      dirofilariosis due to Dirofilaria repens. Nonetheless, the retrospective analysis
      of five locally acquired D. repens infections in dogs, seems to indicate that an
      animal reservoir exist in the area. A feline case imported from Camargue, France,
      is also described. The most common dermatological signs were erythema, alopecia,
      crusting, papulae and nodules. All patients had lesional pruritus and dogs were
      affected by concurrent babesiosis. Eradication of the underlying condition,
      followed by a therapy with the specific adulticide and microfilaricide drugs led
      to a complete recovery of microfilaraemia. Increased pet travel and ecological
      changes are extending the ranges of vector borne, parasitic and zoonotic
      diseases. This fact pose a unique diagnostic challenge for the veterinarian,
      since the index of suspicion may be absent outside endemic areas.

PMID- 14593934
TI  - [Renal amyloidosis caused by Ehrlichia canis].
AB  - An 8 year old, intact female, Old English Sheepdog was presented with lethargy
      and chronic weight loss of one year duration. The dog suffered from recurrent
      fever and a mild peripheral lymphadenopathy. Mild thrombocytopenia, monoclonal
      hyperglobulinemia and positive Ehrlichia canis antibody titer were indicative of
      Ehrlichiosis. The patient developed proteinuria and renal failure, which
      suggested the presence of glomerulopathy. Immunohistochemical staining of renal
      biopsy specimen demonstrated AA amyloidosis. Chronic ehrlichiosis was suspected
      to be the cause of the dog's renal amyloidosis.

PMID- 14593935
TI  - Nursing care of patients with late-stage Parkinson's disease.
AB  - Patients in the late stages of Parkinson's disease may be significantly disabled
      for many years, often because of their increasing inability to tolerate
      therapeutic doses of antiparkinson drugs. Their status and management have been
      overlooked in the literature. Few current healthcare professionals have cared for
      patients with Parkinson's disease in the prelevodopa era and do not understand
      how severe and protracted the illness can be without effective treatment. This
      article describes a practical approach to the nursing management of severely
      affected patients (i.e., Hoehn and Yahr Stage 4-5) who no longer derive
      consistent, therapeutic benefit from their drugs. Specific problems these
      patients face are adverse drug reactions such as postural hypotension, psychosis,
      and confusion, as well as difficulties with nutrition, elimination, mobility and
      falling, communication, sexuality, memory, and mood. Nursing interventions can
      help minimize the effect of these problems on the patient.

PMID- 14593936
TI  - Pentobarbital sodium coma for refractory intracranial hypertension.
AB  - Refractory intracranial hypertension (RICH) is defined as intracranial pressures
      that exceed 25 mm Hg for 30 minutes, 30 mm Hg for 15 minutes, or 40 mm Hg for 1
      minute. RICH occurs in approximately 15% of patients with traumatic brain injury.
      If it is not aggressively treated, RICH can result in cerebral herniation and
      death. Pentobarbital sodium coma is a second-tier treatment that can be used to
      treat RICH. Understanding the principal mechanics of this therapy is key to the
      successful management of RICH and quality patient care.

PMID- 14593937
TI  - Idiopathic intracranial hypertension within the ICF model: a review of the
      literature.
AB  - Idiopathic intracranial hypertension (IIH) is an unusual disease, seen most often
      in women of childbearing age who are obese. If left untreated, IIH can cause
      chronic pain and blindness. Although IIH has been recognized by healthcare
      providers since the late 1880s, the cause is still not known and risk factors
      remain unclear. Treatment has not changed over the years. While professionals
      struggle to define, describe, and successfully treat IIH, persons with the
      disease are struggling to cope. Internet support group communications relate
      numerous personal stories of frustration, depression, pain, anxiety, and
      disability. The World Health Organization's International Classification of
      Functioning, Disability and Health (ICF) model provides an appropriate framework
      through which to view what is known and what is yet to be discovered about IIH.
      The ICF model was designed to complement the International Statistical
      Classification of Diseases and Related Health Problems, looking beyond mortality
      and disease by describing how people live with their health conditions. Applying
      this framework to IIH reveals many opportunities for nursing research within the
      ICF domains of health condition, body function and structure, ability and
      participation, and environmental and personal factors.

PMID- 14593938
TI  - Caring for the patient undergoing transsphenoidal surgery in the acute care
      setting: an alternative to critical care.
AB  - Patients undergoing transsphenoidal surgery have complex needs that require
      expert care and the coordination of a multidisciplinary team of healthcare
      professionals. In general, patients requiring this surgery are cared for in
      intensive care units. An innovative program at the University of Virginia,
      developed 11 years ago, enables these patients to be cared for on an acute care
      unit for the entirety of their hospitalization. The success of this program is
      evident in positive clinical and financial outcomes.

PMID- 14593940
TI  - The role of arginine vasopressin in thermoregulation during fever.
AB  - Fever is common in postoperative neurosurgical patients. When fever is present,
      thermoregulatory responses regulate body temperature within a range that appears
      to have an upper limit. Endogenous substances, such as arginine vasopressin
      (AVP), modulate the thermoregulatory response during fever and are referred to as
      endogenous antipyretics. Endogenous antipyretics attenuate fever by influencing
      the thermoregulatory neurons in the preoptic region and anterior hypothalamus and
      in adjacent septal areas. Well known for its antidiuretic and vasopressive
      properties, AVP plays an important role in antipyresis via the ventral septal
      area of the limbic system. Evidence suggests that there may be a synergistic
      relationship between AVP receptors and cyclo-oxygenase enzyme during antipyresis,
      and the presence of AVP may enhance the efficacy of nonsteroidal antipyretic
      drugs. On the other hand, there is evidence that increased levels of AVP released
      during fever may play a role in febrile seizures. Although the antipyretic effect
      of AVP release during fever is beneficial, excessively high levels of AVP may be
      detrimental.

PMID- 14593939
TI  - Upper cervical spine chordoma: a case study.
AB  - Cervical chordomas are rare, slow-growing, but locally aggressive tumors.
      Predominantly found in people 50-69 years old, a chordoma arises from remnants of
      the primitive notochord. It is most often found in the sacrococcygeal or skull
      base areas. However, it can be found throughout the spine. Because chordomas are
      slow growing, they may reach considerable size before the patient becomes
      symptomatic. Surgical resection with a wide margin is the only curative
      procedure. Usually, because of tumor location and infiltration, this is not
      possible. Although this type of tumor is generally considered radioresistant,
      radiation therapy is often prescribed after surgical resection. The following
      case study illustrates the clinical presentation, surgical interventions, and
      neuroscience nursing considerations for a patient undergoing a posterior
      stabilization as well as a midline mandibulotomy-glossotomy approach for an upper
      cervical spine chordoma resection.

PMID- 14593941
TI  - Maximizing research opportunities: secondary data analysis.
AB  - Knowledge development in nursing can be enhanced by broadening the understanding
      of legitimate scientific inquiry. SDA uses existing data to answer research
      questions and can be especially useful for nurse researchers. Advantages of SDA
      include its potential for resource savings and its cost-effectiveness. Also, the
      investigator can circumvent data collection challenges such as finding
      appropriate participants. However, SDA does not require less rigor. A sound
      conceptualization of the research problem is still required, and identifying and
      obtaining appropriate data for SDA can be quite time-consuming. Nevertheless, SDA
      can be both a practical and appropriate research process that enables nurses to
      maximize their opportunities for answering important clinical questions.

PMID- 14593942
TI  - Multiple responsibilities can counter teen substance use.

PMID- 14593943
TI  - Physical educators teaching health.

PMID- 14593944
TI  - Passage of 100% tobacco-free school policies in 14 North Carolina school
      districts.
AB  - Though comprehensive tobacco-free school policies constitute an important
      component of state tobacco control efforts, little research exists about their
      adoption process. In the past two years, efforts occurred in North Carolina to
      increase the number of school districts adopting 100% tobacco-free school
      policies. As part of the North Carolina Youth Empowerment Study (NC-YES),
      researchers developed a school tobacco policy interview guide to conduct
      interviews with 40 key people (e.g., school board member, principal, etc.) in
      each of 14 school districts that adopted a 100% tobacco-free school policy by the
      end of 2001. Results showed seven districts adopted their school policy in the
      past two years. Seven themes emerged: 1) Catalysts: Local adult and youth
      "champions" facilitated policy change; 2) Process of Adoption: Most school
      policies were adopted with an administrator or other adult initiating the change,
      but youth involvement increased in recent years; 3) Methods of Adoption:
      Advocates personalized health concerns by focusing on children and role modeling
      by adults; 4) Political Leadership: Governors of North Carolina, through letters
      to school districts and a policy summit, played an important role in stimulating
      policy change; 5) Barriers to Adoption: Concerns expressed before policy
      adoption, about teacher attrition or inability to enforce the policy, did not
      occur as feared; 6) Enforcement Issues: A key to policy enforcement involved
      being consistent, supportive, and firm; and 7) Economics of Tobacco
      Farming/Manufacturing: Though a local tobacco economy did little to influence
      policy adoption, districts that adopted policies were not located in counties
      with heavy tobacco production. Public health advocates may use this information
      to encourage school districts to adopt 100% tobacco-free school policies.

PMID- 14593945
TI  - A preliminary survey of health education in Indiana home schools.
AB  - The total US school enrollment of 52.7 million students in 1998 excluded an
      estimated 1.2 million students educated in their homes. In 1989, some 1,148 home
      school families enrolled with the Indiana Department of Education. Just over a
      decade later, some 18,260 home school families had registered, and this number
      continues to increase. Despite knowledge about the growing numbers of families
      choosing to home school, limited empirical data exists of how health education is
      presented in home schools or the needs of home school educators who teach health
      education. This preliminary study examined health education content areas taught
      by home school educators in Indiana. An instrument was developed, piloted, and
      administered to a random sample of 600 home school educators. Results indicated
      most home school educators taught a variety of health education topics. Three
      topics--first aid, physical activity and fitness, and nutrition and diet--were
      taught most frequently in the health curriculum of home schools. Violence
      prevention, suicide prevention, and consumer health were covered less frequently
      in the health curriculum. Health was typically taught in a nonstructured,
      teachable moment format. Implications for coordinated school health programs and
      suggestions for further research are discussed.

PMID- 14593946
TI  - Using Polvika's model to create a service-learning partnership.
AB  - Collaboration can maximize limited resources of universities, school systems, and
      public health departments by offering learning from experience. Polvika's
      theoretical model and principles from Community-Campus Partnerships for Health
      guided development of a service-learning partnership among a university, a county
      health department, and an alternative school in a large public school district.
      Of three commonly identified patterns of service-learning, this partnership
      demonstrated the pattern that equally emphasizes service to a community or
      agency, and mutual learning by all participants. All organizations in the
      partnership share a common goal to optimize the health of children in schools,
      and to provide quality learning for professional students. The partnership is in
      its fourth year. Formal interagency agreements now exist among all partners.
      Individuals continue to demonstrate flexibility and mutual awareness of strengths
      and limitations of respective organizations. Public school students receive more
      services, many high-risk children achieve better learning outcomes, school nurses
      offer expanded services in many schools with the help of nursing students, and
      undergraduate and graduate nursing students gain meaningful learning experiences.
      Some nursing students state that school nursing has become a career goal. The
      partnership continues to evolve to meet changing needs of the partners. Members
      remain satisfied with the collaboration.

PMID- 14593947
TI  - Peer harassment, school connectedness, and academic achievement.
AB  - This study described peer harassment in a large, multiethnic sample of
      adolescents, and explored the relationship between experiencing peer harassment
      and both school connectedness and achievement. Survey data came from 4,746
      students in grades 7-12 at 31 public schools in ethnically and socioeconomically
      diverse communities in a Midwestern state. Frequency of five types of harassment
      were analyzed with data on school connectedness and grades. Multivariate analysis
      controlled for gender, grade level, race/ethnicity, and socioeconomic status.
      Results indicate that most students periodically experience mistreatment; 10% to
      17% report being treated disrespectfully, having others act superior, or being
      insulted at least once per week, and an additional 14% to 22% of students report
      suffering these behaviors a few times per month. Girls, Whites, Native Americans,
      and middle school students reported more harassment than boys, other ethnic
      groups, and high school students, respectively. Peer harassment related
      significantly to both aspects of school life; those who disliked school tended to
      suffer more mistreatment, and "B" students reported the least harassment on
      average. Young people mistreated by peers may not want to be in school and may
      thereby miss out on the benefits of school connectedness as well as educational
      advancement. The high prevalence of peer harassment and its association with
      school connectedness and school achievement provide justification for
      interventions aimed at prevention of peer harassment. A schoolwide approach using
      educational and policy components may provide an appropriate prevention strategy.

PMID- 14593948
TI  - Impact of Promoting Lifestyle Activity for Youth (PLAY) on children's physical
      activity.
AB  - This study examined effects of a school-based intervention called PLAY (Promoting
      Lifestyle Activity for Youth) on physical activity levels and body mass index
      (BMI) of students. Participants included 606 fourth-grade students selected from
      a stratified sample of 35 schools in Arizona and placed into four groups: PLAY &
      PE, PLAY Only, PE Only, and No Treatment. A treatment-control, post-measurement
      design assessed physical activity using the YAMAX pedometer, and height and
      weight data were collected following the intervention. One-way ANOVAs were used
      to analyze the data. Results indicated the treatment was effective at increasing
      the physical activity level of children, especially girls. No significant
      differences between groups were found for BMI. Programs such as PLAY, which can
      increase the activity level of children, may have significant health implications
      for youth.

PMID- 14593949
TI  - School nurses: voices from the health room.

PMID- 14593950
TI  - [Interferon: therapy in patients with cutaneous malignant melanoma in adjuvant
      setting].
AB  - Malignant melanoma still remains a challenge as an increase of the malignant
      disease incidence is noted. Five years after removal of the primary lesion, the
      recurrence of malignant melanoma is observed in 55-80% of patients at high risk
      for the recurrence. Therefore, the 5-year survival rate is 25-70%. These results
      point to the need of searching for optimal adjuvant treatment. Standard
      cytostatics are of no use due to lacking effectiveness in adjuvant treatment.
      Early results of clinical trials (15-20% of objective responses) with interferon
      in the treatment of advanced cutaneous malignant melanoma have created the
      foundations for the determination of the role of this cytokine in adjuvant
      treatment. Adjuvant therapy with low doses of interferon is ineffective with
      respect to neither overall survival time nor disease-free time while high-dose
      interferon immunotherapy increases the overall survival time (as confirmed by two
      randomised trials out of three trials conducted) and disease-free survival. For
      this reason, high-dose interferon immunotherapy should be administered to
      cutaneous malignant melanoma patients at high risk for disease recurrence.

PMID- 14593951
TI  - [Usefulness of the tilt test with nitroglycerine application in diagnosing of
      patients with unexplained syncope: new aspects of the well-known problem].
AB  - INTRODUCTION: The head-up tilt test (TT) performed after sublingual
      nitroglycerine application (NTG) is a tool that is commonly accepted and widely
      used in diagnosing patients with unexplained syncope. Although the results of
      conducted trials suggest advantages related to the protocol of TT with NTG, but
      data concerning the special diagnostic value of this protocol and the
      circumstances when it is superior to the passive TT, have not been established
      yet. The aim of the study was to analyse the problem whether there is, and if so,
      what circumstances it is related to, any special value of TT with NTG in
      diagnosing patients with vasovagal syncope. MATERIAL AND METHODS: 112 subjects
      were examined, 67 men and 45 women, at the mean age 34.4 +/- 19.1, and 42.6 +/-
      17.4 years (p = 0.07), respectively, with at least two events of unexplained
      syncope. The control group consisted of 35 healthy volunteers matched for age and
      sex (18 men and 17 women), at the mean age 39.4 +/- 12.6 years (18-77 years)
      without syncope in anamnesis. All patients underwent a passive tilt test
      (Westminster protocol- 60 degrees/45 min) and in the case of lacking response to
      the passive test, the patients received 0.25 mg NTG and the test was continued
      over the next 20 minutes. The type of syncope reaction was determined based on
      the ACC classification (1996). If vasovagal syncope occurred, its type was
      defined according to the VASIS classification. RESULTS: The passive TT defined
      the reason of syncope in 31 patients (28% of all examined subjects), whereas TT
      with NTG increased this group by another 37 patients (33%), so that 68 patients
      (61%) were diagnosed using both protocols. The analysis of the study population
      that was sensitive to TT revealed that the group of patients who had vasovagal
      syncope during the test was greater than the group of patients who had other,
      i.e. non-vasovagal, type of reaction (48 vs 20, p = 0.002). There was a
      statistically significant relationship between the method of provocation and the
      type of reaction (chi 2 = 6.8, p = 0.009). The age difference between the groups
      of patients who developed vasovagal reaction during passive TT and patients who
      developed this type of reaction during TT with NTG (27.3 +/- 11.5 vs 39.9 +/-
      20.3, p = 0.005) was also statistically significant. In the context of these
      results, concerning the mentioned groups of patients, the dichotomy division
      index of age was established: which was 30 and 50 years, respectively. A
      statistically significant relationship was found between the sex of the study
      population and the type of provocation (passive TT vs TT with NTG) resulting in
      syncope in sensitive patients (chi 2 = 2.84, p = 0.009). Fourteen (70%) women and
      only 23 (48%) men required NTG in order to establish the diagnosis, i.e.
      vasovagal background of syncope. CONCLUSIONS: 1. Vasovagal syncope seems to be a
      highly specific form of circulatory response to TT and requires application of
      NTG statistically more often than other types of neurocardiogenic reactions. 2.
      TT with NTG is especially justified in women and patients of either sex older
      than 50 years.

PMID- 14593952
TI  - [Remote repeatability of tilt test].
AB  - The aim of this study was the assessment of long-term repeatability of tilt-table
      test and parameters of heart rate variability analysis. Westminster protocol tilt
      table test extended with nitroglycerin test was combined with analysis of heart
      rate variability. Five-minute intervals of ECG record were evaluated before and
      after the upright tilting, before syncope and 24-hour record was analysed. The
      test was performed in duplicate in 27 persons including 14 men (mean age 33 +/-
      13.5) at interval of 29 +/- 13 months. The patients were then observed for 14 +/-
      11.4 months. The study subjects were divided into groups with and without the
      recurrence of syncope. Repeatability was observed in 76.5% in positive test
      result and in 70% in negative test result. A low repeatability of positive test
      was observed. Blood pressure, heart rate and heart rate variability analysis
      parameters demonstrated a high repeatability during both tests. The recurrence of
      syncope was observed in 10 (37%) persons. The patients with both tilt tests
      positive, demonstrated recurrence of syncope two times more frequently what makes
      that the identification of the patients at risk for syncope return is easier.

PMID- 14593953
TI  - [The influence of Chlamydia pneumoniae infection on acute coronary syndromes].
AB  - Chlamydia pneumoniae is one of the infectious factors the role of which is
      considered in the process of atherosclerosis and its complications. THE AIM: Of
      the study was to assess the incidence of Ch. pneumoniae infection in the patients
      with acute coronary events. The study was carried out in 36 patients, mean age
      61.2 +/- 13.4 years, 27 men and 9 women hospitalised in our Department with the
      diagnosis of previous or recent acute myocardial infarction. The control group
      consisted of 19 subjects, aged 61.1 +/- 14.3 years, 10 men and 9 women
      hospitalised due to other reasons. In all studied patients during the first 24
      hours venous blood was taken for the assessment of fibrinogen and C-reactive
      protein (CRP) concentrations and titres of IgA and IgG anti-Ch. pneumoniae
      antibodies, and pharyngeal swabs were done for Ch. pneumoniae assessment.
      RESULTS: Positive swab tests were found in 19% of the patients, positive IgG
      titres in 80% and IgA in 64% of the patients. In the control group the
      corresponding values were 11, 79, 42%, respectively. In the patients with
      positive IgG titres, negative IgA titre result was observed in 21% and in the
      control group in 53% (p < 0.05). The CRP level was significantly higher in the
      studied patients than in the control group (24.2 vs 4.2 mg/l; p < 0.05).
      CONCLUSIONS: 1. The high percentage of positive serologic tests and rare positive
      results of pharyngeal swabs indicate a frequent contact with Ch. pneumoniae in
      human population. 2. Ch. pneumoniae infection exerts no significant influence on
      the unspecific markers of inflammation. 3. The higher frequency of seroconversion
      positive IgG and negative IgA titres--in the control group indicates the role of
      prolonged or acute Ch. pneumoniae infection in the development or progression of
      coronary atherosclerosis and its complications.

PMID- 14593954
TI  - [Remodeling of coronary arteries examined by arteries intravascular
      ultrasonography].
AB  - In most papers atherosclerotic remodelling was assessed in one segment of each
      studied artery. Such mode of study makes impossible to investigate the
      homogeneity of the remodelling. The aim of the study was intravital assessment by
      means of intravascular ultrasonography (IVUS) of the incidence of positive and
      negative remodelling in coronary artery segments and verification of the
      hypothesis that remodelling is inhomogeneous within the same artery. METHOD:
      Remodelling was assessed quantitatively by IVUS (3.5 F; 20 MHz Visions Five-64
      F/X catheters, Oracle In-Vision Imaging System, Endosonics Corp. USA) in 48
      segments of 27 coronary arteries. On the base of the difference between total
      vessel area (TA) at lesion site and reference cross-section (plaque area < 35%)
      remodelling was classified as negative, positive or absent. In 13 arteries out of
      27 studied arteries more than 1 segment was assessed, containing both cross
      section with > 50% stenosis and reference cross-section. RESULTS: Positive,
      negative and absent remodelling was observed in 54%, 29% and 17% of segments,
      respectively. The analysis revealed two different types of remodelling in 7 out
      of 13 arteries with several analysed segments. This finding demonstrates that
      remodelling is inhomogenous within the artery (p < 0.006). CONCLUSIONS:
      Compensatory enlargement is the most common response of coronary arteries to
      atherosclerotic plaque development followed by negative remodelling and absence
      of remodelling. Not homogenous remodelling within the same artery suggests a
      prominent role of local factors in determining the type of response of the artery
      to plaque accumulation.

PMID- 14593955
TI  - [Reference values of arterial pressure depending on age, assessed by 24-hour
      ambulatory monitoring].
AB  - 24-hour blood pressure monitoring has been ever more widely used in children.
      However, percentile ranks for healthy children have not been prepared yet. The
      aim of the study was to define percentile ranks of blood pressure measured by
      ambulatory blood pressure monitoring in healthy children aged 7-17 years
      depending on sex in children from the Province of Podlasie. The examinations were
      carried out in a group of 540 children: group I-girls--265, group II boys--275,
      who were divided into subgroups according to age. Blood pressure was measured by
      ambulatory blood pressure monitors: BR-102 f. Schiller, Poland LTD and Quiet
      Tycos, USA according to the principles in force. The results showed that mean
      systolic blood pressure (RRs) increased with age from 103.2 to 117.7 mm Hg in
      girls and from 98.8 to 125.6 mm Hg in boys. The differences were statistically
      significant (p > 0.05). Diastolic blood pressure (RRr) increased less (p > 0.05).
      Mean systolic blood pressure at night was 9-10% and diastolic pressure 10-11%
      lower, irrespective of sex. The range of normal blood pressure values (5-95
      centile) was established. In group I in the youngest girls the range of RRs was
      89-110 mmHg, that of RRr was from 51 to 75 mm Hg while in group II in the
      youngest boys RRs range was from 95 to 108 mm Hg and RRr--from 52 to 73 mm Hg. In
      group I and II in the oldest girls and boys the values were higher. The
      percentile ranks (5-95) were prepared for systolic and diastolic blood pressure
      based on blood pressure monitoring during 24-hours and separately during activity
      (day) and resting time (night). CONCLUSIONS: 1. Systolic blood pressure in
      children aged 7-17 years increases with age more than diastolic blood pressure.
      2. Percentile ranks for healthy children aged 7-17 years depending on age, sex
      and daily time period were established.

PMID- 14593956
TI  - [Microalbuminuria and blood pressure in patients with acute ischemic stroke].
AB  - The study was designed to investigate the association between blood pressure (BP)
      and urinary albumin excretion in patients with acute ischaemic stroke. A group of
      54 patients were studied with first-ever ischaemic stroke, admitted within 24
      hours after the onset of symptoms. Urinary albumin excretion was measured
      immunonephelometrically on the second day of hospitalisation in 24-hour urine
      collection. BP was measured on admission and then every 4 hours during 48 hours
      after admission. Microalbuminuria (MA) was found in 23 patients (42.5%).
      Microalbuminuric patients had higher BP during 48 hours after admission than
      patients without MA (P < 0.05, ANOVA with repeated measures). Mean daytime
      diastolic BP values (88.6 +/- 9 vs 82.7 +/- 9) as well as night-time systolic
      (148.0 +/- 18 vs 134.3 +/- 15) and diastolic BP (88.5 +/- 10 vs 80.4 +/- 7) were
      higher in patients with MA (p < 0.05, Student t-test). Patients with MA
      demonstrated no physiological decrease of night-time systolic and diastolic BP,
      contrary to those with normal urinary albumin excretion. Mean night-time systolic
      and diastolic BP correlated with urinary albumin excretion (rs = 0.37, p = 0.006
      and rs = 0.39, p = 0.004, respectively, Spearman's rank correlation coefficient).
      On multivariate analysis the night-time diastolic BP was the most important
      factor influencing the occurrence of microalbuminuria (p = 0.007, logistic
      regression model).

PMID- 14593957
TI  - [The impact of carnitine on serum ammonia concentration and lipid metabolism in
      patients with alcoholic liver cirrhosis].
AB  - Treatment of patients with liver cirrhosis with the signs of liver insufficiency
      is complex and seldom satisfactory. Carnitine, taking part in liver lipid
      metabolism might be a potentially effective drug. THE AIM: Of the study was to
      evaluate the influence of L-carnitine on serum ammonia, cholesterol and
      triglyceride concentrations. PATIENTS AND METHODS: Fifty patients with liver
      cirrhosis of alcoholic aetiology, 16 females and 34 males, aged 55 +/- 11.3 years
      (mean +/- SD) were included into the study. Fourteen patients were treated with L
      carnitine, 25--with L-ornitine L-aspartate, 11--were not given those medicaments.
      All patients had proteins reduced down to 0.5 g/kg b.w. per day in their diet.
      The serum concentrations of ammonia, cholesterol and triglycerides were assessed
      on inclusion and after 28 days of treatment. RESULTS: All patients improved
      clinically. A significant improvement was observed in the group of patients
      treated with L-ornitine L-aspartate (p < 0.003), and among those treated with L
      isocarnitine (p = 0.005), while evaluating the Child-Pugh score before and after
      treatment. The serum ammonia concentration decreased in all patients. However,
      among the individuals treated with L-carnitine an increase of serum cholesterol
      and triglyceride concentrations was observed as well (p = 0.02). CONCLUSIONS: L
      carnitine lowers the serum ammonia concentration and improves lipid metabolism.

PMID- 14593958
TI  - [Efficacy and safety of combined statin-fenofibrates therapy compared with
      monotherapy in patients with mixed hyperlipidemia and high risk of coronary heart
      disease].
AB  - In most patients with mixed hyperlipidemia and coronary heart disease (CHD) the
      treatment targeted both at triglyceride and LDL cholesterol levels is very
      difficult, when one lipid-lowering drug is used. We performed a prospective study
      evaluating the efficacy and safety of statins (simvastatin 20 mg, fluvastatin 40
      mg, lovastatin 20 mg, atorvastatin 10 mg) and fibrates (fenofibrate 200 mg,
      ciprofibrate 100 mg) used alone, and then compared with statin-fibrate
      combinations in 180 patients. Each of three periods of therapy lasted 8-12 weeks.
      All regimens of statins and fibrates normalised the lipid profile more
      effectively than monotherapy. Monotherapy with statins lowered total cholesterol
      by 23.8% in relation to the baseline; compared with 13% for fibrates monotherapy
      and 34.3% for statins plus fibrates combinations. Triglyceride concentration
      decreased by 25.5% with statins alone, 34.0% with fibrates alone and 44.5% with
      combined therapy. LDL cholesterol was reduced by 28.1%, 12.7%, 40.3%,
      respectively. Statins increased HDL cholesterol by 4%, fibrates by 18% and
      combined therapy by 15.2%. The target levels for LDL cholesterol were achieved in
      3.7% patients on statins therapy, in 1.1% on fibrates and 21.7% on the combined
      therapy. For total cholesterol the changes were 8.3%, 2.2% and 41.7%,
      respectively and for triglycerides the were 27.7%, 45% and 66.7%, respectively.
      The safety of the treatment was assessed by recording adverse events and
      measuring clinical laboratory parameters. No significant increase in CPK or ALT
      levels was observed. Only 7 patients had a history of moderate ALT increase (< 3
      times) and 27 of CPK increase (< 3 times) when receiving combined statins plus
      fibrates. CONCLUSIONS: We conclude that combined therapy with statins and
      fibrates can improve lipid abnormalities in mixed hyperlipidaemia more effective
      then statins or fibrates monotherapy. The combined therapy was well tolerated and
      safe.

PMID- 14593959
TI  - [Changes of the position and length of the transverse colon causing abdominal
      pain and chronic constipation during adolescence].
AB  - In 12 patients aged 9 to 17 years (14.1 +/- 2.3 SD years) (11 girls, 1 boy)
      complaining of abdominal pain and chronic constipation, barium large bowel X-ray
      examination showed the following anatomical and positional abnormalities: ptosis
      of the transverse colon to the small pelvis was found in 11/12 patients, ptosis
      of the hepatic flexure of the transverse colon (2/12), ptosis of both the hepatic
      and lienal flexures (2/12), dolichocolon (2/12), and dolichosigma (2/12); 10 of
      12 children had symptoms characteristic of irritable colon syndrome. It seems
      that clinical symptoms accompanying these abnormalities begin to manifest mainly
      in girls during adolescence because at that time the final length of the colon is
      established, the transit time reaches its maximal value, and the shape of the
      pelvis becomes characteristic for this gender. These abnormalities are rather
      constitutional than acquired since previously it has been reported that the
      vertical ptosis of the kidney(s) occurs also mainly in adolescent girls.

PMID- 14593960
TI  - [The results of conservative treatment of oxalate urolithiasis in children].
AB  - Hyperoxaluria is defined as urinary oxalate excretion exceeding 0.45 mmol/1.73
      m2/day and accounts for 15% of recurrent urolithiasis. There have been only a few
      reports on the prevalence and treatment of oxalate urolithiasis in children. THE
      AIM: Of the study was to assess the efficacy and safety of the protocol of
      intensive and combined treatment of hyperoxaluria in children. MATERIAL AND
      METHODS: Seventeen children at the mean age of 11.5 +/- 4.5 years with positive
      history of urolithiasis and diagnosis of hyperoxaluria were studied. In this
      group hyperoxaluria was an isolated defect in 9 of 17 children, but in 3/17 it
      was accompanied by hyperuricosuria, in 5/17 by hypomagnesuria and in 1 case by
      hypercalciuria. During the 12-month period the children were intensively hydrated
      and received a low-oxalate diet and supplemental therapy with vitamin B6,
      magnesium, citrates and lactic acid bacteria preparations. RESULTS: In all but
      one child oxaluria decreased below 0.45 mmol/1.73 m2/day (decrease by 45%). No
      new stone formation was seen during the observation period. In all patients
      abdominal pain and haematuria subsided. CONCLUSIONS: We conclude that the
      intensive, complex, conservative treatment of hyperoxaluria in children is
      effective and safe. It allows to decrease hyperoxaluria and prevent the
      recurrence of urolithiasis.

PMID- 14593961
TI  - [Histological clinical features of the primary tumor as prognostic factors in
      patients with laryngeal carcinoma].
AB  - Poland is the country where a constant increase of the incidence of laryngeal
      cancer and subsequent deaths has been observed during the last 30 years. Despite
      the large number of therapeutic and histopathological studies that have been
      performed, there are currently no clinical or morphologic markers available to
      predict the outcome in patients with laryngeal carcinoma. The aim of the study
      was to analyse the examinations of tissues from 209 patients who were treated
      surgically because of advanced carcinoma of the larynx to create a system of
      tumour evaluation, useful for prognostication. The examinations included routine
      histology, Anneroth, Batsakis and Luna's modified classification and morphologic
      grading at the tumour front (TFG). The authors have analysed the tumour biologic
      and host-related factors to determine the potential usefulness of these features
      in predicting local and nodal recurrences and survival in patients with laryngeal
      cancer. This study indicates that the mode and depth of invasion, lymphocytic and
      eosinophil infiltration, lymph node metastases and score of the tumour front
      grading and Anneroth, Batsakis and Luna's modified classification are important
      prognostic parameters in the assessment of recurrences and survival in squamous
      cell carcinoma of the larynx.

PMID- 14593962
TI  - [Gabapentin in the treatment of neuropathic pain in patients with type 2 diabetes
      mellitus].
AB  - STUDY AIM: Assessment of pain relief in type 2 diabetes mellitus patients with
      neuropathic pain treated with gabapentin at daily dose 2400 mg. MATERIAL AND
      METHODS: 26 patients with type 2 diabetes mellitus and painful neuropathy were
      included into the study. The duration of pain symptoms ranged from 1 to 3.5 years
      (mean 1.9 +/- 0.6 year). Pain intensity was assessed using Short-Form McGill Pain
      Questionnaire (SFMPQ), visual analogue scale (VAS), and Present Pain Intensity
      Scale (PPI) before the study and after 6-week treatment with gabapentin. The
      sensory and motor conduction studies, electromyography from tibial anterior
      muscle and skin sympathetic response were recorded in the patients and compared
      with the results obtained from the control group. RESULTS: The neurophysiological
      examinations carried out in the patients with sensory neuropathy demonstrated a
      significant conduction impairment in sensory and motor nerves as well as in
      sympathetic sweat-secreting nerves. After six weeks of gabapentin treatment in
      2400 mg daily dose a significant pain reduction was observed, assessed by means
      of SF-MPQ, VAS and PPI questionnaires. The authors have demonstrated a
      significant analgesic effect of gabapentin in patients with diabetic neuropathy
      and the suggest administration of this preparation in chronic diabetic neuropathy
      in order to improve the quality of patients' life.

PMID- 14593963
TI  - [Evaluation of gastric motility in obesity].
AB  - There are conflicting information about differences of gastric emptying rate
      between lean and obese subjects and lack of information concerning antral
      motility in both groups. It has been suggested that obesity is associated with an
      altered rate of gastric emptying, but the results of earlier studies examining
      gastric emptying rates in obesity have proved inconsistent. AIM: The purpose of
      this study was to compare gastric emptying rate and antral motility in obese and
      lean subjects. MATERIALS AND METHODS: Gastric antral motility and gastric
      emptying were measured after consumption of sweet omelette in 2 groups of
      patients: 10 obese (BMI mean = 33.18) and 10 lean subjects (BMI mean = 22.16)
      using a scintigraphic technique. Lag phase was assessed by physiologic and
      mathematic approach. Gastric area was calculated using a computer programme
      (Diacam-Siemens). RESULTS: There was no difference in gastric emptying profiles;
      the mean gastric contents after 2 hours of assessment in obese and lean groups
      was 69% and 71.6%, respectively. Gastric antral motility parameters such as
      contraction amplitude and frequency, relaxation and contraction time were not
      differing between the groups. Only in the 90th minute of the assessment a
      significant difference in contraction time was found. There were also no
      differences in gastric area and duration of lag phase. No significant correlation
      between height, BMI, gastric area and body area was found in both groups.
      CONCLUSIONS: There are no differences in the rate of gastric emptying and gastric
      antral motility between lean and obese subjects. No correlation between BMI,
      height, body area and gastric area was found. This findings deny the common
      opinion suggesting that obese people have bigger stomach which empties more
      rapidly than in lean subjects.

PMID- 14593964
TI  - [Apolipoprotein E and tau protein in vascular dementia].
AB  - In 33 patients meeting the NINDS-AIREN criteria of possible diagnosis of vascular
      dementia (VD) ApoE genotype and tau protein level in cerebrospinal fluid were
      determined. The frequency of e4 allele occurrence in a group of VD patients was
      16.6% and it was not statistically significant in comparison with control group.
      In the group patients with VD tau protein level in cerebrospinal fluid was 33.5
      pg/ml while in the control group the level amounted to 32.5 pg/ml. The difference
      between these two groups was not statistically significant. The authors emphasize
      that ApoE e4 and tau protein level determination is not very useful in the
      differential diagnosis of dementia.

PMID- 14593966
TI  - [Occupational exposure to HIV among Polish surgeons from the province of West
      Pomerania].
AB  - In order to establish appropriate strategies making possible to reduce the risk
      of HIV infection in operating suite an attempt was undertaken at determination of
      the incidence of occupational exposure to blood among surgeons and of the factors
      that have influence on the occurrence of such events. The questionnaire study
      included 200 physicians from hospitals both in the City of Szczecin and in the
      Province of West Pomernia. Most responders (97.5%) answered that they had at
      least one skin damage over the year preceding the study (median of cuts--10)
      including 87% that had at least one needle puncture and 24% that had over 10
      punctures. The number of cuts was independent of such variables as: gender, age,
      degree of speciality, working place or training on HIV/AIDS (p > 0.07), however,
      a correlation was demonstrated with specialisation degree, number of operating
      hours and number of HIV-positive patients treated. With respect to the most
      recent occupational injury it was found that: it occurred most frequently in the
      operating room during elective operation, it was never reported, it involved the
      main operator and was self-inflicted. The high number of occupational skin
      injuries observed among the studied physicians points to the need of modification
      of current professional practices and of systematic training of the staff in
      protection against HIV infection.

PMID- 14593965
TI  - [Plasmin-alpha 2-antiplasmin complexes in blood of patient with lichen planus
      against the background of other fibrinolysis parameters].
AB  - The aim of the present study was to evaluate fibrinolysis in patients with lichen
      planus. In blood of 20 patients (12 women, 8 men) the levels of tissue type
      plasminogen activator (t-PA), plasmin-antiplasmin complexes (PAP) and D-dimer
      were examined. The control group consisted of 37 healthy volunteers. The
      concentrations of t-PA, PAP and D-dimer were higher in patients with lichen
      planus in comparison with the control group. It seems that increased level of t
      PA antigen in the blood of the patients with lichen planus was the effect of t-PA
      releasing from endothelial cells. The results of the present study suggest that
      increased concentrations of t-PA antigen, PAP and D-dimer were the evidence of
      higher activity of fibrinolysis system in subjects with lichen planus.

PMID- 14593967
TI  - [The location of components of fibrinolytic system in laryngeal cancer].
AB  - Laryngeal cancer is the most common neoplasm of the head and neck region.
      Laryngeal cancer patients experience thromboembolic complications more often than
      the general population. Our previous studies revealed in loco activation of blood
      coagulation in laryngeal cancer. The purpose of the present study was to examine
      the interactions among the laryngeal cancer cells and fibrinolytic system
      components in loco. Twenty-two cases of squamous carcinoma of the larynx were
      examined. AMeX method-preserved cancer tissues were examined using
      immunohistochemical ABC method. Fibrin and D-D fibrin dimers were demonstrated in
      the matrix, predominantly on the tumor-host front. Plasminogen, tissue-type
      plasminogen activator (t-PA) and plasmin were detected in cancer cells, but the
      intensity of their expression revealed a negative correlation with the degree of
      malignancy. A weak expression of high molecular weight urokinase (HMW-UK) was
      observed in cancer cells in the centers of the cancer foci, and a product of its
      degradation--low molecular weight urokinase (LMW-UK) was observed in cancer cells
      on the invasion front. The presence of plasminogen activator inhibitors (PAI-1,
      PAI-2, PAI-3) was also documented in the cancer cells. The expression of
      urokinase receptor (u-PAR) was very weak. Based on the results of the study, we
      suggest that in laryngeal cancer a suboptimal activation of fibrinolysis occurs
      that contributes to fibrin deposition in the tumour.

PMID- 14593968
TI  - [The serum concentration of transforming growth factor beta1, interleukin 12 and
      interleukin 5 in children with chronic hepatitis B].
AB  - The aim of the study was to evaluate the serum TGF-beta 1, IL-12 and IL-5
      concentration in children with chronic hepatitis (ChH) B. The study included 62
      children with histopathologically diagnosed chh B. The stage of fibrosis and
      inflammation grade were assessed according to Batts and Ludwig and Ishak et al.
      The control group consisted of 9 children without clinical signs of infectious
      and chronic diseases. Serum TGF-beta 1 concentration was significantly elevated
      in patients with chronic hepatitis B (p = 0.0077) as compared to controls; there
      were no significant differences in serum concentrations of IL-12 and IL-5 between
      the examined groups of children. There was also no correlation between serum
      concentration of the studied cytokines and the degree of fibrosis, inflammation,
      activity of GPT, GOT, ALP, GGTP and concentrations of bilirubin, proteins or
      immunoglobulins (G, A, M).

PMID- 14593969
TI  - [The role of extracellular matrix components in the T-cell activation in systemic
      sclerosis].
AB  - Patients with systemic sclerosis (SSc) show, in addition to tissue fibrosis, a
      variety of distinct vascular and immunological abnormalities. Extracellular
      matrix proteins (ECM) play an important role in the regulation of cell migration
      and expression of various genes involved in activation of immune reactions. The
      aim of our study was to examine the co-stimulatory effects of ECM components
      (type I and IV collagen, laminin, fibronectin) in patients with SSc and to
      examine the expression of beta 1-integrins (VLA-2/CD49b, VLA-3/CD49c and VLA
      5/CD49e) on PBMC in these patients. We examined 66 patients with various types of
      SSc and 62 healthy volunteers. The results showed that fibronectin and type I
      collagen had the highest co-stimulatory activities in both SSc patients and
      controls, whereas laminin and type IV collagen were less potent co-stimulatory
      agents. Flow cytometry data showed an increased expression of integrins (VLA-2,
      VLA-3, VLA-5) in SSc T-cells in comparison to healthy volunteers. The results of
      the proliferation assays in patients with SSc and normal volunteers showed that
      only fibronectin stimulated CD3--dependent lymphocyte response. Fibronectin co
      stimulated T-cell proliferation in patients with SSc which may be dependent on
      increased expression of integrins CD49c or CD49e or/and level of circulating T
      cells bearing these markers. Increasing of the expression of integrins on PBMC
      can help their migration to the perivascular spaces and can stimulate them.
      Fibronectin could enhance activation of PBMC followed by production of some
      cytokines involved in fibrosis in SSc.

PMID- 14593971
TI  - [Risk factors of myocardial infarction in 28 years old man].
AB  - Ischaemic heart disease in the young people is connected with family
      cardiovascular risk factors disease. The young 28 years old male, who was
      presented, has myocardial infarction treated by primary angioplasty and stent
      implantation. The control angiography was performed 4 month later, restenosis in
      stent was observed. Patient had family risk factors and arterial hypertension,
      dyslipoproteinemia, which was not treated before and after myocardial infarction.
      The doctors informed him about risk factors and modifications in patient's life
      style.

PMID- 14593970
TI  - [Dramatic symptoms of pheochromocytoma in old woman during antiarrhythmic therapy
      with sotalol: case report].
AB  - We present the case of 81-years old woman with diabetes mellitus and moderate
      hypertension who reported multiple syncope's. Cerebral and metabolic causes of
      syncope's were excluded and the patient was diagnosed to have sick sinus
      syndrome. After implantation of the cardiac pacemaker the treatment with sotalol
      was started. After introducing the antiarrhythmic drug the frequency of syncopes
      increased dramatically and blood pressure rose unusually (up to 250/140 mm Hg).
      Subsequently phaeochromocytoma was suspected. Laboratory data as well as computed
      tomography confirmed the diagnosis of left adrenal tumour. After successful
      surgery the blood pressure normalized and the patient recovered uneventfully. The
      reported cases describes the difficulties in diagnosing phaeochromocytoma in
      elderly people with multiple different accompanying diseases.

PMID- 14593972
TI  - [Potential role of environmental and occupational pollutants in the etiological
      pathogenesis of idiopathic pulmonary fibrosis].
AB  - Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and usually fatal
      lung disease of no identifiable etiology, which is characterised by fibroblast
      proliferation and extracellular matrix accumulation resulting in irreversible
      distortion of the architecture of the lung. Some studies suggest the role of
      various environmental exposure and occupational pollutants in the
      etiopathogenesis of IPF. However, other studies fail to confirm these
      observations. This article is a review of studies searching for potential
      etiological factors of IPF in the environment in the place of living and place of
      working. It seems, that conflicting results of these studies make impossible to
      determine the potential role of environmental and occupational pollutants in the
      pathogenesis of IPF.

PMID- 14593973
TI  - Memantine for dementia?
AB  - Memantine (Ebixa--Lundbeck Ltd), an oral medicine, is available in the UK for
      treating "patients with moderately severe to severe Alzheimer's disease". It
      differs from other licensed dementia medicines in that it is an N-methyl-D
      aspartate (NMDA) receptor antagonist. The company has claimed that, with
      memantine therapy, "improvements in activities of daily living help patients to
      maintain a degree of independence and be easier to care for, potentially avoiding
      the need for nursing home care". We assess the efficacy of memantine for dementia
      and discuss its place in the management of patients with Alzheimer's disease.

PMID- 14593974
TI  - Acne, isotretinoin and depression.
AB  - At any one time, most 16-18-years-old and up to half of adults have acne. In 60%
      of all teenagers, the condition will be sufficiently severe for them to self
      treat or seek medical advice. Up to half of 12-20-year-olds with acne develop
      psychological or social problems. Oral isotretinoin, which is used for the
      treatment of severe acne, might be expected to improve psychological functioning.
      However, there have been suggestions that the drug itself might cause depression
      and suicide. Here we consider these concerns, and the implications for the use of
      isotretinoin when managing patients of all ages.

PMID- 14593975
TI  - Intravenous magnesium for acute asthma?
AB  - Each year in the UK, around 1,500 people die from asthma. Standard treatment has
      been based on bronchodilators (e.g. beta 2-stimulants) and anti-inflammatory
      drugs (corticosteroids). The recently revised British Guideline on the Management
      of Asthma suggests also using a single dose of i.v. magnesium sulphate in
      patients with acute severe asthma, an unlicensed indication. Here we discuss the
      rationale for giving i.v. magnesium and whether it offers any advantage for
      patients with acute severe asthma.

PMID- 14593976
TI  - Managing heparin-induced thrombocytopenia: preventing life- and limb-threatening
      thrombosis. Introduction.

PMID- 14593977
TI  - Overview of heparin-induced thrombocytopenia.
AB  - A brief overview of the pathophysiology, diagnosis, and treatment of heparin
      induced thrombocytopenia (HIT) is discussed. Following any exposure to
      unfractionated heparin or low-molecular-weight heparin (LMWH), HIT, a serious
      allergic drug reaction, may occur. The frequency of HIT is thought to range from
      1 to 5% of patients receiving heparin. This immune-mediated syndrome is
      paradoxically associated with thrombosis, not bleeding, with thrombin generation
      playing a central role. The diagnosis of HIT is based upon clinical findings that
      can be confirmed with laboratory assay; however, when there is clinical suspicion
      of HIT, all forms of heparin therapy should be immediately discontinued and
      initiation of alternative anticoagulation is strongly encouraged. In the presence
      of HIT, the use of LMWHs or initiation of warfarin without additional effective
      anticoagulation is not recommended. Argatroban and lepirudin, two direct thrombin
      inhibitors (DTIs), are approved by the Food and Drug Administration for the
      management of HIT. Both agents have been studied in the treatment and prevention
      of thrombotic events associated with HIT. Argatroban, a univalent inhibitor of
      thrombin, is eliminated via the liver, while lepirudin, the first DTI approved
      for HIT, is a bivalent thrombin inhibitor that is cleared by the kidneys. Neither
      argatroban nor lepirudin demonstrates cross-reactivity with heparin-induced
      antibodies, and both DTIs have been associated with effective anticoagulation and
      platelet recovery in patients with HIT. The appropriate use of DTIs in HIT
      reduces the risk of thrombotic events and severe consequences associated with
      this serious drug reaction.

PMID- 14593978
TI  - Treatment options for heparin-induced thrombocytopenia.
AB  - Appropriate management, as well as efficacy and safety, of heparin-induced
      thrombocytopenia (HIT) and prevention of severe consequences with argatroban and
      lepirudin are discussed. Heparin-induced thrombocytopenia, a serious immune
      mediated drug reaction, can occur as an isolated incident (isolated HIT) or with
      acute thrombosis sometimes referred to as HIT and associated thrombosis syndrome
      (HITTS). Due to the severe consequences associated with HIT, appropriate
      management is critical. Argatroban and lepirudin, two direct thrombin inhibitors
      (DTIs), are currently FDA approved for use in patients with HIT. The clinical
      experience with these agents is critically examined in this article. The safety
      and efficacy of argatroban in management of HIT were the subject of a single
      published clinical trial. The study was designed to reflect conventional clinical
      practice, whereby treatment of patients with HIT was initiated upon clinical
      suspicion. In several of these patients, HIT antibodies could not be
      demonstrated. Compared to historical controls, argatroban demonstrated efficacy
      in patients with isolated HIT; however, no differences were observed in HIT
      patients with acute thrombosis. Rates of bleeding episodes did not differ between
      argatroban and control. The clinical efficacy and safety of lepirudin have been
      the subject of three clinical trials and one large drug monitoring program.
      Lepirudin has demonstrated benefit in HIT patients with or without existing
      thromboembolism. Bleeding rates were higher than in the historical control.
      However, bleedings requiring transfusion did not differ. Although no direct head
      to-head comparison trials of argatroban and lepirudin have been conducted,
      parallels can be drawn between the agents based on careful review of published
      clinical trials. Consistently, rates of new thrombosis, limb amputation, and
      death appear to be lower in patients treated with lepirudin as compared with
      those treated with argatroban, whereas the risk for major bleeding per patient
      day seems to be similar with both DTIs.

PMID- 14593979
TI  - Direct thrombin inhibitor therapy in the cardiovascular patient.
AB  - Direct thrombin inhibitors in cardiovascular patients are discussed. Patients
      presenting with acute coronary syndromes (ACS) of ST- and non-ST-segment
      elevation myocardial infarction (STEMI and NSTEMI, respectively) or unstable
      angina develop mural thrombi within minutes of plaque disruption or erosion.
      Initial acute therapy includes heparin and aspirin. Up to 60% of patients have
      coronary revascularization to reduce the high risk of death, new myocardial
      infarction (MI), or recurrent angina. In addition, heparin may initiate a serious
      allergic, prothrombotic drug reaction, heparin-induced thrombocytopenia (HIT), in
      1-5% of patients. Acute cessation of heparin and initiation of direct thrombin
      inhibitor (DTI) therapy for suspected HIT are vital and well established. Several
      clinical trials comparing DTIs with heparin have been done in ACS and
      percutaneous coronary intervention (PCI), and have shown excellent potency in
      inhibiting thrombus formation and reducing coronary events. An overview of
      results from published studies evaluating the use of bivalent and univalent DTIs
      in the cardiovascular patient is presented. Four DTIs are discussed: two r
      hirudins (lepirudin and desirudin), both bivalent with stable chain and renal
      excretion; bivalirudin, bivalent with rapid-chain metabolism; and argatroban,
      univalent with hepatic metabolism. The extensive clinical experience with r
      hirudin in cardiovascular patients suggests that it is an excellent choice for
      managing patients with HIT and is easy to use in converting to warfarin, since it
      does not significantly change the prothrombin time.

PMID- 14593980
TI  - Clinical utility of subcutaneous hirudins.
AB  - The clinical utility of subcutaneous hirudins is discussed. The term "hirudins"
      refers to a class of antithrombotic agents structurally derived from the
      medicinal leech salivary protein hirudin. Breakthroughs in biotechnology over the
      past 20 years have resulted in the development of recombinant versions of hirudin
      (r-hirudin). Lepirudin is one such r-hirudin that is identical to natural hirudin
      except for the substitution of leucine for isoleucine at the N-terminus and the
      elimination of a sulfate group on the tyrosine at position 63. Another r-hirudin,
      desirudin, is identical to hirudin except for a valine-valine in the N-terminus
      and the absence of the sulfate group on tyrosine at position 63. Both r-hirudins
      are bivalent and tightly bind to both the catalytic site and the exposite of
      thrombin to exert their inhibitory effects on thrombin. Unfractionated heparin
      (UF) and low-molecular-weight heparins (LMWHs) are widely used in medical and
      surgical patients to prevent and treat arterial and venous thrombotic events.
      Besides bleeding, the major adverse effect of heparins is heparin-induced
      thrombocytopenia (HIT). HIT is associated with a paradoxical hypercoagulable
      state and marked risk of clinical thrombosis. Management of HIT requires the
      immediate cessation of all heparin exposure, and the initiation of an alternative
      anticoagulant. Because r-hirudins are effective agents and do not cross-react
      with HIT-associated antibodies, they are excellent anticoagulants in patients
      with past or current HIT. Clinical trials have also demonstrated the efficacy and
      safety of subcutaneous (s.c.) r-hirudins compared to heparins in non-HIT
      settings. Results of these trials support the use of r-hirudin therapy in
      patients with HIT or at risk of developing HIT. Additionally, case reports have
      described safe and effective use of s.c. r-hirudin therapy in the outpatient
      setting in both HIT and non-HIT patients.

PMID- 14593981
TI  - [Dog-days: when the sun becomes the enemy].

PMID- 14593983
TI  - [Which antiretroviral strategy to use in adults?].

PMID- 14593984
TI  - [Compliance stakes for the nurse. Interview by Helene Delmotte].

PMID- 14593985
TI  - [Chronicle of passing time... Twenty five years of stomatherapy education].

PMID- 14593986
TI  - ["Suspicious deaths" in infants: national study].

PMID- 14593987
TI  - [Diabetics' pyramid...!].

PMID- 14593988
TI  - [Oral hygiene].

PMID- 14593989
TI  - [Confidential and free screening centers. Listening and daily prevention].

PMID- 14593990
TI  - [Arteritis: better screening].

PMID- 14593993
TI  - The changing face of infectious disease. New threats, new science.

PMID- 14593994
TI  - Enfuvirtide, an HIV-1 fusion inhibitor.

PMID- 14593995
TI  - Bacterial meningitis in children with cochlear implants.

PMID- 14593996
TI  - Aortic stenosis, von Willebrand factor, and bleeding.

PMID- 14593997
TI  - Microsatellite instability in colon cancer.

PMID- 14593998
TI  - Microsatellite instability in colon cancer.

PMID- 14593999
TI  - Patients who refuse food and fluids to hasten death.

PMID- 14594000
TI  - Struggling Global Fund approves grants for HIV, TB, and malaria. But board
      meeting is marred by warnings about shortfalls and accusations of political
      manoeuvering.

PMID- 14594001
TI  - Can Zerhouni create a bold, risk-taking NIH? To succeed, reforms will have to
      change NIH's organisation and culture.

PMID- 14594002
TI  - Silicone breast implants may be close to US approval.

PMID- 14594003
TI  - [Cancer chemotherapy in the future. Discussion].

PMID- 14594004
TI  - Argentina and Cuba agree on trade of "drugs for dollars".

PMID- 14594005
TI  - Spanish government approves frozen embryo research.

PMID- 14594006
TI  - Measles immunisation strategies to expand.

PMID- 14594007
TI  - Conference highlights bioterrorist threat.

PMID- 14594008
TI  - Commission recommends reform of German health care. Proposed deep cuts in
      services and higher tax contributions highly unpopular with public.

PMID- 14594009
TI  - Thoughts on "The effect of blood drawing techniques and equipment on the
      hemolysis of ED laboratory blood samples".

PMID- 14594010
TI  - Bibliography. Current world literature. Genetics and epidemiology.

PMID- 14594011
TI  - Bibliography. Current world literature. Skin and eye.

PMID- 14594012
TI  - Rising caesarean section rates: a cause for concern?

PMID- 14594013
TI  - Research reawakens ecstasy neurotoxicity debate.

PMID- 14594014
TI  - Microsoft cofounder provides 100 million US dollars for brain-gene atlas.

PMID- 14594015
TI  - Directors of NINDS engaged in top-down planning.

PMID- 14594016
TI  - Fluoroscopically guided interlaminar cervical epidural injections.

PMID- 14594017
TI  - Recent publications in hematological oncology.

PMID- 14594018
TI  - [55 years ago. Anatomo-clinical study of 2115 gynecologic patients. Vol. III, No.
      2 March-April 1948, pp. 299-316].

PMID- 14594019
TI  - Medical devices; immunology and microbiology devices; classification of the
      endotoxin assay. Final rule.
AB  - The Food and Drug Administration (FDA) is classifying the endotoxin assay into
      class II (special controls). The agency is taking this action in response to a
      petition submitted under the Federal Food, Drug, and Cosmetic Act (the act) as
      amended by the Medical Device Amendments of 1976 (the amendments), the Safe
      Medical Devices Act of 1990 (SMDA), the Food and Drug Administration
      Modernization Act of 1997 (FDAMA), and the Medical Device User Fee and
      Modernization Act of 2002 (MDUFMA). The agency is classifying this device into
      class II (special controls) in order to provide a reasonable assurance of safety
      and effectiveness of the device. Elsewhere in this issue of the Federal Register,
      FDA is announcing the availability of a guidance document that will serve as the
      special control for the device.

PMID- 14594020
TI  - Enfuvirtide, a new treatment for HIV infection.
AB  - Enfuvirtide is the first in a new class of drugs called fusion inhibitors. It was
      recently approved in Canada for the treatment of patients with evidence of HIV-1
      replication despite ongoing antiretroviral therapy. Current evidence on safety
      and efficacy is limited to 48-week studies. Two phase III trials found that in
      treatment-experienced patients failing antiretroviral treatment, the addition of
      subcutanous enfuvirtide to an optimized oral background antiretroviral regimen
      significantly reduced viral load and increased CD4 cell counts. Potential high
      cost and limited supply may reduce access to this treatment.

PMID- 14594021
TI  - Mortality trend of pancreas cancer in Japan: 1960-2000.

PMID- 14594022
TI  - APOE epsilon4 as a predictor of subjective quality of life in a biracial older
      person community sample.
AB  - The epsilon4 allele of apolipoprotein E (APOE) has been associated with health
      related outcomes that may adversely affect quality of life (QOL) in older adults.
      In the absence of published information, we sought to determine whether the
      epsilon4 allele was associated with subjective QOL across 5 parameters in a
      community sample of older adults. DESIGN: Prospective cohort study. SETTING:
      Community-based sample of older adults in North Carolina (Duke site of the
      Established Populations for Epidemiologic Studies of the Elderly [Duke EPESE]).
      PARTICIPANTS: Self-responding genotyped sample members (n = 1,880) of whom 1,254
      provided longitudinal data. MEASUREMENTS: APOE genotype and five newly
      constructed, reliable, and valid measures of subjective QOL derived from the Duke
      EPESE questionnaire. The 5 parameters measured were social, economic, mental and
      physical health, and functional status. Control variables included age, gender,
      race (African American or White), education and urban/rural residence. RESULTS:
      Among those with good baseline QOL, there was no significant association between
      the epsilon4 allele and any of the parameters of subjective QOL in longitudinal
      analyses. In controlled longitudinal analysis, older age women predicted poorer
      functional status; being African American, and reporting lower education
      predicted poorer subjective economic well-being; and being African American
      predicted better self-assessed mental health. CONCLUSIONS: This study is among
      the first to explore the association of the epsilon4 allele with overall QOL.
      Considered from a public health perspective, these findings challenge the
      uncritical assumption that the presence of this susceptibility gene in the
      population implies an excess burden of poor QOL. The findings do not contradict
      the previous association of epsilon4 with Alzheimer's disease (AD) and other
      conditions. Such conditions continue to merit full attention.

PMID- 14594023
TI  - Asking neutral versus leading questions: implications for functional limitation
      measurement.
AB  - National surveys of older Americans routinely have included functional limitation
      items using either a leading approach ("how much difficulty do you have...") or a
      neutral approach ("do you have any difficulty..."). This article evaluates the
      performance of scales based on these two approaches. METHODS: Using responses
      from 595 randomly selected participants to the 1994 Health and Retirement Study,
      the authors compared prevalences and evaluated scales based on each approach with
      respect to the extent of missing data, face validity, reliability, predictive
      validity, convergent validity, and robustness of odds ratios in predictive
      models. RESULTS: The authors found that leading questions provided higher
      estimates of functional limitations than neutral questions, but both approaches
      yielded scales with similar validity and reliability. However, for both
      approaches, scales incorporating degree of difficulty had better validity and
      reliability than those based on counts of tasks. All four approaches yielded
      substantially similar coefficients in a model predicting disability onset.
      DISCUSSION: The authors conclude that, because they minimize survey time without
      compromising validity and reliability, items that explicitly capture degree of
      difficulty by asking "How much difficulty do you have..." may be the optimal
      approach for survey designers.

PMID- 14594024
TI  - Depressive symptoms and physical health of caregivers of persons with cognitive
      impairment: analysis of reciprocal effects over time.
AB  - Research indicates that caregivers of persons with cognitive impairment are at
      elevated risk for clinical depression. The current study examines the association
      between physical illness and depressive symptoms among caregivers over a 5-year
      interval. METHODS: Participants were recruited as part of a longitudinal study of
      dementia prevalence in Canada (N = 382). Persons with cognitive loss and their
      primary caregivers were randomly identified from each Canadian province. RESULTS:
      Subsequent to control for sociodemographic variables, patient illness
      characteristics and initial depressive symptomatology, baseline health of
      caregivers contributed significantly to the prediction of depressive symptoms
      five years later. In contrast, depressive symptomatology was not a significant
      predictor of physical health over this same interval (again controlling for
      sociodemographic variables, patient illness characteristics, and caregivers'
      health at baseline). DISCUSSION: These analyses provided partial support for
      reciprocal effects between physical illness and depression. Findings are
      discussed in terms of the applicability of a model of reciprocal effects to older
      adults.

PMID- 14594025
TI  - Opening the black box of rationing care in later life: the case of 'community
      care' in Britain.
AB  - Research on the rationing of care to older patients in Britain and America
      typically focuses on acute care here I consider 'chronic care' as illustrated by
      'community care' in Britain. Adopting a critical sociological approach to
      dependency and to the construction of 'later life,' I argue that chronic care
      users constitute a class, and that clinical need has played a pivotal role in its
      development. As this reflects the allocative rationing of care I call into
      question, the claim made by the current British government that need can provide
      a benchmark of age justice.

PMID- 14594026
TI  - Effects of simulated weightlessness on myosin heavy chain expression of soleus
      intrafusal muscle fibers in rats.
AB  - OBJECTIVE: To examine the myosin heavy chain expression in intrafusal fibers in
      rat soleus muscle before and after simulated weightlessness and to analyse the
      mechanism involved in muscle spindle deterioration during simulated
      weightlessness. METHOD: The rats were divided into 3 groups: 7 d, 14 d tail
      suspension group and control group. Control and experimental spindles were
      examined using monoclonal antibodies specific for myosin heavy chains of slow
      tonic (ALD58) and fast-twitch (MF30) chicken muscles by the immunoperoxidase
      reaction utilizing the ABC (avidin-biotin-complex) method. RESULT: The extrafusal
      muscle fibers did not exhibit immunoreactivity to ALD58 and MF30. Only intrafusal
      fibers bound these antibodies. The bag 1 fiber and bag 2 fiber reacted to ALD58.
      The bag 2 fiber and chain fibers stained with MF30. After 7 d suspension the
      immunoreactivity of the bag 1 fiber and bag 2 fiber to ALD58 decreased, while the
      immunoreactivity of the bag 2 fiber and chain fibers to MF30 increased. After 14
      d suspension the immunoreactivity of the bag 1 fiber and bag 2 fiber to ALD58
      decreased remarkably, even disappeared. While all of the intrafusal fibers
      reacted to MF30 and the immunoreactivity increased obviously. CONCLUSION: The
      expression level and patterns of MHC in intrafusal fibers of rat soleus muscle
      changed after simulated weightlessness.

PMID- 14594027
TI  - Changes of cardiac catecholamines in rats after repeated +Gz exposures and
      protective effects of low-G preconditioning and tea polyphenols.
AB  - OBJECTIVE: To observe whether repeated +Gz exposures could induce metabolic
      disorder of cardiac catecholamines in rats as well as the protective effects of
      low-G preconditioning and tea polyphenols (TP). METHOD: Thirty-two male Wistar
      rats were randomly divided into 4 groups (n=8): group A (control), only submitted
      to +1 Gz 5 min; group B (+10 Gz stress), exposed to +10 Gz 30 s, 5 times/d with
      +1 Gz 1 min interval, 3 d/wk, for 3 wk in total; group C (low G preconditioning),
      +Gz stress parameters were the same to that of group B, but the rats were
      submitted to +2 Gz 5 min 1 h prior to +10 Gz exposure; group D (TP protection), +
      Gz stress parameters were the same to that of group B, but TP was given orally to
      the rats at the dose of 200 mg/kg 1 h prior to +10 Gz exposure. These animals
      were decapitated on the next morning of the last centrifuge run, and the hearts
      were taken out and stored in liquid nitrogen immediately. The contents of
      noradrenaline (NA), adrenaline (AD), dopamine (DA) and serotonin (5-HT) in
      myocardial tissue were determined using HPLC with electrochemical detector.
      RESULT: Compared with group A, AD level in group B increased significantly (P <
      0.01), but there were no significant differences of NA, DA and 5-HT contents
      between the two groups. Compared with group B, the myocardial contents of AD and
      5-HT were decreased significantly in group C and D (P<0.01), while myocardial DA
      concentration in group D increased significantly (P<0.01). CONCLUSION: Repeated
      +10 Gz exposures could induce metabolic disorder of catecholamines in rat heart,
      especially the increase of AD level. Low-G preconditioning and natural
      antioxidant TP had significant protective effects.

PMID- 14594028
TI  - Volume rendering based on sorted volumetric data.
AB  - OBJECTIVE: To describe a spatial data structure called sorted volumetric data
      structure which speeds up the volume rendering and will not affect image quality.
      METHOD: Before volume rendering we transfer each slice of volume into an array
      indexed by the value of voxels, element in which stores the position of each
      voxel. According to the opacity transfer function, we can affirm the value ranges
      of voxels that are non-transparent. Therefore we translate, resample and
      composite only the voxels in the value ranges. By marching through the sorted
      arrays, we locate the non-transparent voxels rapidly and skip all voxels that are
      transparent. The sorted data structures need not recompute whenever the opacity
      transfer function changes and are not restricted on the opacity transfer
      function. RESULT: The method presented in this paper has been implemented in a
      standard personal computer. The rendering time for CT head volume data is less
      than 1 s that is satisfied with the diagnostic purpose. CONCLUSION: The concept
      of proposed algorithm is simple, easy to realize and it is not recomputed
      whenever the opacity transfer function changes. By using the sorted volumetric
      data structure, we speed up the volume rendering without affecting image quality.

PMID- 14594029
TI  - [Changes of dentin, dental pulp and periodontium tissue in tail-suspended rats].
AB  - OBJECTIVE: To investigate the metabolic changes of calcium and phosphorus in
      dentin, dental pulp and periodontium in tail-suspended rats, and the functions of
      TGF-beta 1, c-fos, collagen-I and collagen IV in dentin, dental pulp and
      periodontium. METHOD: Relative percentage contents of Ca, P in dentin, dental
      pulp and periodontium were measured with scanning electron microscope and energy
      spectrum analytical system in 3 groups of rats. The expression of TGF-beta 1, c
      fos, collagen-I and collagen IV were also observed. RESULT: In the suspension
      group, the relative percentage content of Ca declined significantly, while P
      increased slightly. There were no significant differences of Ca, P in alveolar
      bone. The expressions of TGF-beta 1, c-fos and collagen-I declined, but the
      expression of collagen-IV in pulp vessel increased. There were no significant
      changes of expressions of TGF-beta 1, c-fos, collagen-I and collagen-IV in the
      vicinity of PDL. After adopting artificial countermeasures, the above expressions
      restored partly. CONCLUSION: Weightlessness might cause abnormal mineralization
      in dentin, and 1.5 G artificial countermeasures could eliminate the above changes
      of mineral metabolism. The poor mineralization of dentin might be associated with
      the reduced secretion of TGF-beta 1, c-fos and collagen-I in tail-suspended rats.

PMID- 14594030
TI  - [Changes of potassium channel activity of hindlimb arterial smooth muscle cells
      in tail-suspended rats].
AB  - OBJECTIVE: To examine the change of potassium channel function in hindlimb
      arterial smooth muscle cells in tail-suspended rats and to elucidate the
      underlying electro-physiological mechanisms responsible for the depressed
      vascular responsiveness of hindlimb arteries induced by simulated weightlessness.
      METHOD: The contractile responsiveness of femoral arterial rings of 1-wk and 4-wk
      tail-suspended rats to potassium channel blockers, tetraethylammonium chloride
      (TEA) and 4-aminopyridine (4-AP), were recorded, and the currents of large
      conductance calcium-dependent potassium channel (BK(Ca)) and voltage activated
      potassium channel (Kv) of vascular smooth muscle cells (VSMCs) in saphenous
      arteries from 1-wk tail-suspended rats were recorded using the whole cell
      recording mode of patch clamp technique. RESULT: The femoral arteries from of 1
      wk and 4-wk tail-suspended rats showed a decreased contractile response to 60 mM
      KCl, and the ratio of their contractile responses induced by TEA or 4-AP to their
      responses induced by 60 mM KCl increased significantly after 1-wk and 4-wk
      simulated weightlessness. However no difference was found between 1-wk and 4-wk
      tail-suspended rats. The whole cell current recording showed that BK(Ca) current
      densities and K(v) current densities of VSMCs in saphenous artery increased
      significantly after 1-wk simulated weightlessness. CONCLUSION: The contractile
      response of hindlimb arteries to KCl decreased after simulated weightlessness.
      The activities of BK(Ca) and K(v) of smooth muscle cells in hindlimb arteries
      from tail-suspended rats increased, and these changes might be among the electro
      physiological mechanisms involved in the depressed vasoreactivity of hindlimb
      arteries due to simulated weightlessness.

PMID- 14594031
TI  - [Effects of simulated weightlessness and mechanical loading on bone interstitial
      fluid flow in rats].
AB  - OBJECTIVE: To investigate the effects of simulated weightlessness and mechanical
      loading on bone interstitial fluid flow. METHOD: Thirty-six male Sprague-Dawley
      [correction of Spargue-Danley] rats were divided into 3 groups: the control
      group, the tail-suspension group, and the tail-suspension plus mechanical loading
      group, with four rats in each group. All the rats were injected via a lateral
      tail vein with horseradish peroxidase on the 21st day of the experiment. Tibial
      tissue specimens were explanted, fixed, decalcified and cut into 30 micrometers
      frozen sections 3 h after the intravenous injection. RESULT: There were less
      peroxidase reaction product in the bony matrix and bone lacunae in tail-suspended
      rats than the control and tail-suspended plus mechanical loading rats.
      CONCLUSION: Tail-suspension decreased fluid movement through the bone, while
      mechanical loading increased it.

PMID- 14594032
TI  - [Changes of osteocalcin in bone and bone marrow in tail suspended rats].
AB  - OBJECTIVE: To study osteocalcin [correction of osteocakin] (OC) changes in bone
      and marrow and calcium deposition in bone and cartilage under simulated
      weightlessness. METHOD: Twenty SD rats were randomly divided into 14 d and 28 d
      tail suspension group and 2 corresponding control groups. Histological samples
      were in situ hybridized and trichrome stained. RESULT: OC expression of bone and
      marrow of rats were lower in tail suspended rats than that in the control
      (P<0.05). OC expression in 14 d tail suspended rats were higher than that in 28 d
      tail suspended group (P<0.05). Mineralization was inhibited, and demineralization
      of femur [correction of furmer] and cartilage mineralized matrix was prominent.
      Demineralization was more prominent in 28 d group. CONCLUSION: OC levels in bone
      and marrow of rats were lower after tail suspension. Calcium deposition was
      inhibited in bone and cartilage. Demineralization was prominent after long term
      hindlimb unloading.

PMID- 14594033
TI  - [Effects of exercise training during 21 d -6 degrees head down bed rest on
      dynamic posture equilibrium and motor coordination].
AB  - OBJECTIVE: To study the effects of 21 d -6 degrees head down bed rest (HDBR) with
      exercise training on dynamic posture equilibrium and motor coordination. METHOD:
      Ten healthy young men were randomly divided into HDBR control groups and HDBR
      exercise groups, with 5 in each group. The subjects in the exercise group
      performed exercise with a bicycle ergometer in the supine position 1 h/d during
      bed rest. Dynamic posture equilibrium as well as isokinetic concentric muscular
      strength were determined before and after 21 d HD-BR. RESULT: After HDBR, average
      dynamic proprioception score and dynamic motor coordination decreased
      significantly, relative peak torque (peak torque /body weights PT/BW) also
      decreased significantly and accompanied with increase of the peak torque ratio
      between hamstrings and quadriceps (H/Q) in HDBR control groups. Average dynamic
      proprioception score and dynamic motor coordination in the HDBR exercise groups
      remained above the HDBR control groups, but the H/Q ratio showed no significant
      change. CONCLUSION: The results showed that exercise training during 21 d -6
      degrees head-down tilt bed-rest do have beneficial effects on retaining the
      dynamic posture equilibrium and dynamic motor coordination of the subjects after
      bed rest.

PMID- 14594034
TI  - [Changes of bone morphogenesis proteins and transforming growth factor-beta in
      hind-limb bones of 21 d tail-suspended rats].
AB  - OBJECTIVE: To investigate changes of bone morphogenesis proteins (BMP),
      transforming growth [correction of grouth] factors-beta (TGF-beta) in tibia and
      the growing of femur in tail-suspended rats after 21 d simulated weightlessness.
      METHOD: Fourteen male SD rats were randomly divided into control group (CON) and
      tall-suspension group (TS). After 21 d tail-suspension, basic physical parameters
      of the femur were measured; changes of BMP, TGF-beta in tibia were assayed by
      immunohistochemical method. RESULT: During 21 d tail-suspension, all rats grew
      well without apparent stress reaction. After 21 d weightlessness simulation, wet
      weight, dried weight, ash, diameter and density of femur in TS group declined
      significantly (P<0.01). Immunohistochemical results of tibia showed that both BMP
      and TGF-beta declined in tissues from all regions of the tibia. CONCLUSION: After
      21 d tall-suspension, the growth of rat's weight bearing bones were suppressed,
      production and secretion of BMP and TGF-beta was holdback.

PMID- 14594035
TI  - [Effects of Qiang Gu Kang Wei prescription on morphology of bone in rats under
      simulated weightlessness].
AB  - OBJECTIVE: To investigate effects of Qiang Gu Kang Wei prescription on bone
      morphology in tail-suspended rats. METHOD: Rats were tail-suspended (-30 degrees)
      for 21 d to simulate weightlessness. The effects of this prescription on
      thickness of periost and cortex at epiphyseal plate of tibial shaft and 3 mm
      under it were examined. The effects of this prescription on histology and
      ultrastructure of tibia were also observed. RESULT: Compared with the normal
      control, cortex at both epiphyseal plate of tibial shaft and 3 mm under it in
      suspended rats thinned significantly (P<0.01 or P<0.05). Histological observation
      showed that in bone of suspended rats, uncalcific matrix was more, bone cells'
      number was lower and their appearance was more infantile, osteoblasts were less
      and smaller, while osteoclasts were more and larger, haversian system of
      transection also showed more irregular than in bone of normal control.
      Ultrastructure observation showed that the function of osteoblasts was inhabited
      and that of osteoclasts was active. All the three doses groups of the
      prescription could increase cortex at either epiphyseal plate of tibial shaft or
      3 mm under it (P<0.01 or P<0.05) compared with the tail-suspended group. The
      appearance of bone in the three groups was improved as well under optical or
      electron microscope. CONCLUSION: This prescription could improve abnormal change
      in bone morphology resulted from being tail-suspended in rats and make it normal.

PMID- 14594036
TI  - [Effects of modafinil on visual and auditory reaction abilities and subjective
      fatigue level during 48 h sleep deprivation].
AB  - OBJECTIVE: To investigate the effects of modafinil, a new central stimulant, on
      visual and auditory motion reaction ability and subjective fatigue level during
      48 h sleep deprivation (SD). METHOD: Six male healthy young volunteers were
      exposed to two 48 h periods of continuous wakefulness during the crossover
      experiment. In one period, three 200 mg doses of modafinil were given and in the
      other, separated by two weeks, matching placebos were administered. The SD time
      started from 7:00 of the first day to 7:00 of the third day. Drugs were given at
      0:00, 16:00 of the second day and 0:00 of the third day. Variables, including
      visual and auditory motion reaction time, attention distribution, critical
      flicker fusion frequency (CFF), Stanford sleepiness scale (SSS) and rating of
      perceived exertion (RPE), were tested at 21:00 of the first day and 1, 3, 5, 7 h
      after each drug administration. RESULT: After 2-3 does of modafinil, the CFF
      level was obviously enhanced while the scores of Stanford sleepiness scale and
      RPE were markedly reduced. The visual and auditory motion reaction ability, as
      well as the attention distribution, showed no significant change. CONCLUSION:
      Modafinil can effectively reduced the subjective fatigue and sleepiness levels
      during SD.

PMID- 14594037
TI  - [Development of self-generating lower body negative pressure device].
AB  - OBJECTIVE: To develop a kind of self-generating lower body negative pressure
      device. METHOD: The device consists of a flexible bellows, reinforced by several
      steel rings and sealed by gasproof adhesive plaster. An adjustable valve, a one
      way flap valve, shoulder straps and handles are incorporated on the top of the
      bellows. The user's lower body was contained in the bellows. As the user's legs
      were extended, the bellows was elongated and the air pressure in it decreased.
      RESULT: Negative pressures of -58, -46, -38 and -26 mm-Hg respectively was
      created with the adjustable inlet valve completely closed, one-quarter open, half
      open, or fully open. CONCLUSION: This self-generating lower body negative
      pressure device combines exercise and LBNP into one thing and is safe and easy to
      use. It might be used in preventing cardiovascular deconditioning during
      spaceflight or for anti-G training of pilots.

PMID- 14594038
TI  - [Changes of endocrine hormones during -6 degrees head down bed rest in human].
AB  - OBJECTIVE: To investigate changes of endocrine hormones during 7 d head down bed
      rest (HDBR). METHOD: Six healthy male volunteers served as the subjects and
      experienced 7 d -6 degrees HDBR. Urine was collected from 6:00-22:00 and from
      22:00-6:00. Serum was collected 48 h before HDBR, 48 h and 120 h during HDBR.
      Then the endocrine indices in urine and serum were determined. RESULT: 1) The
      levels of serum CORT and ALD increased at 48 h during HDBR, while serum T3, T4,
      TP, UN decreased but they all recovered to normal at 120 h during HDBR. 2) The
      level of urine CORT, ALD and NE reached its peak in 24-48 h, and then gradually
      decreased to normal level. CONCLUSION: The endocrine indices in serum and urine
      changed in the early period but returned to normal level gradually with the
      proceeding of HDBR.

PMID- 14594039
TI  - [Experimental research on the effects of hydrophobic coating porous plates on
      heat dissipation of water sublimator].
AB  - OBJECTIVE: To investigate the development method of hydrophobic coating porous
      plates for water sublimator and carry out an experimental study on hydrophobic
      coating porous plates. METHOD: Porous plates were coated with Teflon coating
      solution and a kind of special hydrophobic coating solution. Physical
      characteristic tests for hydrophobic coating porous plates were conducted. An
      upgrading breadboard of sublimator was redesigned. Effects of hydrophobic coating
      porous plates on heat rejection of water sublimator were studied. RESULT:
      Hydrophobic coating porous plate could evidently increase the water retention
      pressure, but also increase pressure drop of gas permeability in varying degrees.
      Heat rejection performance of two kinds of coating plates was different.
      Performance of coating plate with the special hydrophobic coating solution was
      better. CONCLUSION: Hydrophobic coating porous plate could improve performance of
      water sublimator by optimizing coating parameters and technics of Teflon coating
      solution and the special hydrophobic coating solution.

PMID- 14594040
TI  - [Effects of field viewing angles on object judgement [correction of jubgerent] in
      virtual environment].
AB  - OBJECT: To investigate the effect of viewing angle on human judgement reliability
      for objects in virtual environment. METHOD: Firstly, pre-tests were done with the
      PC virtual reality ergonomic system to determine difference among observed object
      and values of viewing angle. Then, one factor, 4-levels full random experiments
      were done with 45 health human subjects (male and female nearly 1:1). RESULT: It
      was shown that the reliability of human judgement was significantly influenced by
      the setting of the viewing angle of virtual environment, and the object judgement
      including size and angle judgement was the best when the viewing angle of virtual
      environment was 60 degrees. CONCLUSION: When virtual reality was used in
      ergonomic design, operation training and other related research, the effect of
      field viewing angle should be taken into consideration, and 60 degrees is
      recommended to be optimal for human judgment task.

PMID- 14594041
TI  - [Development of a shock response spectrum test facility].
AB  - OBJECTIVE: To develop a shock response spectrum test facility for testing space
      products in the pyrotechnic environments. METHOD: The natural frequencies of the
      resonant plate, a key part of the facility, were calculated with finite element
      method. The dynamic response of the whole system was simulated when the machine
      was excited by a real shock generated by a dropping hammer. A shock response
      spectrum test facility was developed under the guide of the simulation results.
      RESULT: The resonant plate drop machine could simulate pyrotechnic shock by
      adjusting the force, the natural frequencies of the plate and the damping
      materials above and under the plate. CONCLUSION: The agreement between the
      measurement and the simulation indicates that the computer simulation results are
      reliable. It is feasible to use the resonant plate drop machine to simulate
      pyrotechnic environment.

PMID- 14594042
TI  - [Integrated evaluation on system reliability of a space metabolism simulation
      device].
AB  - OBJECTIVE: To define the lower confidence limit of the system reliability of the
      space metabolism simulation device by using the test data of the comprising units
      in their development phases. METHOD: A new method for defining the environmental
      conversion factors of failure times has been given basing on the AMSAA model, and
      the MTBF point evaluated values and lower confidence limits of the units were
      defined, at last, the lower confidence limit of the system reliability was
      obtained using L-M method. RESULT: The lower confidence limit of the system
      reliability under confidence level of 0.8 is 0.9281, which is consistent with the
      result obtained by the classic system reliability evaluation method. CONCLUSION:
      Integrated system reliability evaluation using the proposed method can well
      satisfy the need in engineering.

PMID- 14594043
TI  - [Spatial and temporal characteristic of eye movement in human-computer interface
      design].
AB  - OBJECTIVE: To examine the related spatial and temporal characteristics of eye
      movement in HCI design and to provide ergonomic parameters to optimize the HCI
      design based on eye tracking. METHOD: Task time, selected error and timeout
      numbers were recorded automatically, when 12 participants were performing the
      task of target selection, with different object size, space and dwell time.
      RESULT: It was significantly found that task time was influenced by object size
      and dwell time, the selected error was influenced by object space and dwell time
      significantly. CONCLUSION: The dwell time, object size and object space are all
      important to optimize the HCI design based on eye tracking. We recommend that the
      dwell time should be 500 ms, the object size and object space should be not less
      than 1.5 degrees and 1.0 degrees respectively for the normal interactive systems.

PMID- 14594044
TI  - [Changes of serum IL-1, IL-2R and TNF-alpha levels in divers after 150 m Heliox
      saturation -182 m excursion in the open sea diving].
AB  - OBJECTIVE: To observe the change of the serum IL-1, IL-2R and TNF-alpha levels in
      divers after deep saturation in the open sea diving. METHOD: Eight divers
      experienced 150 in Heliox saturation -182 in excursion diving. Serum levels of IL
      1, IL-2R and TNF-alpha level before and after diving were measured by ELISA.
      RESULTS: There was no significant change of serum TNF-alpha level after
      saturation diving, but serum levels of IL-1, IL-2R increased significantly after
      saturation diving. CONCLUSION: Deep open sea saturation diving had significant
      effects on serum IL-6, IL-2R levels of the divers.

PMID- 14594045
TI  - [Progress and application of free radical determination techniques in the
      biological domain].
AB  - Seeking for convenient, rapid and highly effective techniques of free radical
      determination is a key point for studying the biologic mechanism of free
      radicals. This paper reviewed the progress of these techniques in biological
      domain and described the electron spin resonance imaging [correction of imagine]
      (ESRI) technique development since the 1990s.

PMID- 14594046
TI  - [30th anniversary of the Japanese journal of cancer and chemotherapy
      publications].

PMID- 14594047
TI  - [Medical abortion--the first Norwegian experiences].
AB  - BACKGROUND: Medical abortion was first introduced in Norway in April 1998. The
      aim of this study is to assess the efficacy, side effects and acceptability of
      medical abortion with mifepristone and vaginally administered misoprostol in a
      Norwegian population. MATERIALS AND METHODS: The study included the first
      consecutive 226 women with gestational age of < 63 days who requested non
      surgical abortion in the first year at the first Norwegian hospital using this
      regime. All women received a single dose of mifepristone 600 mg orally followed
      by 800 microgram of misoprostol vaginally after 48 hours. Complications were the
      principal outcome measure. We also took note of side effects such as abdominal
      pain and bleeding and inquired about how acceptable the treatment was for the
      women concerned. RESULTS: 95 % of the women had an uncomplicated termination of
      their pregnancies. The side effects were few and tolerable and the method's
      acceptability high. INTERPRETATION: The combination of mifepristone and vaginally
      administered misoprostol is effective and safe, has few side effects, and is well
      accepted by Norwegian women.

PMID- 14594048
TI  - [The initial prodrome in schizophrenia--core dimensions of experience and
      behavior].
AB  - BACKGROUND: In order to identify and possibly prevent psychosis at prodromal
      stages, it is important to learn how patients and families perceive initial
      prodromes, particularly the prodromal subjective experiences. MATERIALS AND
      METHODS: We explore prodromal phenomena and identify potential core dimensions in
      19 first-episode DSM-IV schizophrenia patients and describe experiences and
      behaviour that appear to be essential components of initial prodromes. RESULTS
      AND INTERPRETATION: The subjects reported serious difficulties interpreting and
      talking about prodromal experiences at the time when they occurred; this caused
      delayed identification, the reasons for which we report. Out of eight groups of
      prodromal experiences we highlight two as tentative core dimensions: [disturbance
      of perception of self] and [extreme preoccupation by and withdrawal to overvalued
      ideas]. Four potential dimensions of prodromal behaviour are also identified: (1)
      leaving school, university or job, or major school truancy, (2) marked and
      lasting observable shift of interests, (3) marked and lasting social passivity,
      withdrawal, or isolation, and (4) marked and lasting change in global appearance
      or behaviour.

PMID- 14594049
TI  - Laser-induced breakdown spectroscopy: an introduction to the feature issue.

PMID- 14594050
TI  - Spatial characterization of laser-induced plasmas by deconvolution of spatially
      resolved spectra.
AB  - The spatial characterization of laser-induced plasmas, including their
      temperature, electron density, and relative atom density, has been carried out by
      emission spectroscopy. The plasmas were generated with iron samples in air and
      argon at atmospheric pressure. An imaging spectrometer equipped with an
      intensified CCD detector procured spectra with spatial resolution. The plasma
      characterization was made at three temporal gates (2-3, 5-6, and 9-11 micros) to
      permit the plasma's evolution to be studied. A deconvolution procedure was
      developed to transform the measured intensity, integrated along the line of
      sight, into the radial distribution of emissivity. Temperature and electron
      density distributions were obtained under the assumption of local thermodynamic
      equilibrium and Stark broadening of the emission lines. The relative atom density
      distributions in the plasma of the Fe atoms arising from the sample and of the Ar
      atoms arising from the ambient gas were determined and evidenced an important
      interaction between the plasma and the surrounding atmosphere.

PMID- 14594051
TI  - Kinetic modeling of the laser-induced breakdown spectroscopy plume from metallic
      lead.
AB  - We report initial results of a study aimed toward developing a computational
      fluid dynamics (CFD) model to simulate the laser-induced breakdown spectroscopy
      (LIBS) plume for the purpose of understanding the physical and chemical factors
      that control the LIBS signature. The kinetic model developed for modeling studies
      of the LIBS plume from metallic lead includes a set of air reactions and ion
      chemistry as well as the oxidization, excitation, and ionization of lead atoms.
      At total of 38 chemical species and 220 reactions are included in the model.
      Experimental measurements of the spatial and temporal dependence of a number of
      lead emission lines have been made of the LIBS plume from metallic lead. The
      mechanism of generation of excited Pb states in the LIBS plume is analyzed
      through kinetic modeling and sensitivity analysis. Initial CFD model results for
      the LIBS plume are presented.

PMID- 14594052
TI  - Experimental and theoretical investigation of laser-induced plasma of a titanium
      target.
AB  - We present a theoretical approach to interpreting optical emission spectroscopy
      measurements for nonequilibrium conditions. In this approach both the fluid
      dynamics and the kinetics of laser-induced plasma are taken into account, and the
      results obtained by the numerical model are applied to the spectroscopic
      observation of the plasma induced by the interaction between a KrF laser and a
      metallic Ti target. We have generalized the theoretical method to calculate the
      initial conditions for the plume expansion that show the best agreement with
      experimental results.

PMID- 14594054
TI  - Computational fluid-dynamic model of laser-induced breakdown in air.
AB  - Temperature and pressure profiles are computed by the use of a two-dimensional,
      axially symmetric, time-accurate computational fluid-dynamic model for nominal 10
      ns optical breakdown laser pulses. The computational model includes a kinetics
      mechanism that implements plasma equilibrium kinetics in ionized regions and
      nonequilibrium, multistep, finite-rate reactions in nonionized regions. Fluid
      physics phenomena following laser-induced breakdown are recorded with high-speed
      shadowgraph techniques. The predicted fluid phenomena are shown by direct
      comparison with experimental records to agree with the flow patterns that are
      characteristic of laser spark decay.

PMID- 14594053
TI  - Influence of Er:YAG and Nd:YAG wavelengths on laser-induced breakdown
      spectroscopy measurements under air or helium atmosphere.
AB  - Laser-induced breakdown spectroscopy (LIBS) is widely dependent on the conditions
      of its implementation in terms of laser characteristics (wavelength, energy, and
      pulse duration), focusing conditions, and surrounding gas. In this study two
      wavelengths, 1.06 and 2.94 microm, obtained with Nd:YAG and Er:YAG lasers,
      respectively, were used for LIBS analysis of aluminum alloy samples in two
      conditions of surrounding gas. The influence of the laser wavelength on the laser
      produced plasma was studied for the same irradiance by use of air or helium as a
      buffer gas at atmospheric pressure. We used measurements of light emission to
      determine the temporally resolved space-averaged electron density and plasma
      temperature in the laser-induced plasma. We also examined the effect of laser
      wavelength in two different ambient conditions in terms of spectrochemical
      analysis by LIBS. The results indicate that the effect of the surrounding gas
      depends on the laser wavelength and the use of an Er:YAG laser could increase
      linearity by limiting the leveling in the calibration curve for some elements in
      aluminum alloys. There is also a significant difference between the plasma
      induced by the two lasers in terms of electron density and plasma temperature.

PMID- 14594055
TI  - Measurement and analysis of OH emission spectra following laser-induced optical
      breakdown in air.
AB  - The measured emission spectra of the OH radical subsequent to laser-induced
      optical breakdown in air are analyzed to infer spectroscopic temperature and
      species number density. Emissions from the UV A2sigma+ --> X2IIi transition
      dominate the spectra in the wavelength range of 306-322 nm and for time delays
      from the optical breakdown of 30-300 micros. Contributions from other species to
      the recorded OH emission spectra were also investigated for spectroscopic
      temperature measurements in the range of 2000-6000 K and for OH number densities
      in the range of 10(14) - 2 x 10(16) cm(-3). Monte Carlo simulations are applied
      to estimate errors in the analysis of the hydroxyl spectra.

PMID- 14594056
TI  - Balmer series Hbeta measurements in a laser-induced hydrogen plasma.
AB  - Stark-broadened emission profiles of the Balmer series Hbeta lines are measured
      subsequent to nanosecond laser-induced optical breakdown in gaseous hydrogen.
      Electron number densities are found from time-resolved spectra from Hbeta
      emissions to be in the range 10(15)-10(18) cm(-3). These results are compared
      with Halpha measurements for which number densities as high as 10(19) cm(-3) are
      determined from Stark widths and Stark shifts. Good agreement is reported for
      number densities inferred from Halpha and Hbeta emissions, down to an electron
      number density 3 x 10(16) cm(-3), by accurate treatment of ion dynamics in the
      theory.

PMID- 14594057
TI  - Imaging of the expansion of femtosecond-laser-produced silicon plasma atoms by
      off-resonant planar laser-induced fluorescence.
AB  - Planar laser-induced fluorescence measurements were used to investigate the
      expansion dynamics of a femtosecond laser-induced plasma. Temporally and
      spatially resolved measurements were performed to monitor the atoms that were
      ablated from a silicon target. A dye laser (lambda = 288.16 nm) was used to
      excite fluorescence signals. The radiation of an off-resonant transition (Si
      390.55 nm) was observed at different distances from the target surface. This
      allowed easy detection of the ablated Si atoms without problems caused by
      scattered laser light. Abel inversion was applied to obtain the radial
      distribution of the Si atoms. The atom distribution in the plasma shows some
      peculiarities, depending on the crater depth.

PMID- 14594058
TI  - Application of frustrated total internal reflection devices to analytical laser
      spectroscopy.
AB  - Novel implementations of single-fiber laser-induced breakdown spectroscopy and
      laser-induced fluorescence spectroscopy systems that gated light switches based
      on frustrated total internal reflection are described. The switching devices are
      largely wavelength independent, with full temporal and spatial separation of
      laser and fluorescence light. Wavelength-independent beam separation or beam
      combination schemes can be implemented for coaxial optical setups, e.g., in
      single-fiber or telescopic experimental arrangements. Selected practical examples
      of schemes for qualitative and quantitative analytical spectroscopy are
      discussed.

PMID- 14594059
TI  - Comparison of nonintensified and intensified CCD detectors for laser-induced
      breakdown spectroscopy.
AB  - The performance and sensitivity of an intensified CCD array system and a
      nonintensified CCD array detector system are compared for laser-induced breakdown
      spectroscopy (LIBS). LIBS measurements were recorded in a calcium-based aerosol
      seeded gas stream at ambient pressure. The signal-to-noise ratio based on the
      393.37-nm calcium emission line was calculated as a function of detector delay
      with respect to the plasma-initiating laser pulse. Both ensemble-averaging and
      single-shot spectral analyses were performed. For all conditions, the intensified
      CCD system provided an enhanced signal-to-noise ratio compared with the
      nonintensified CCD system.

PMID- 14594060
TI  - Conditional data processing for single-shot spectral analysis by use of laser
      induced breakdown spectroscopy.
AB  - Schemes of conditional data processing are evaluated based on either the peak-to
      base ratio or the signal-to-noise ratio as a metric for analyte detection in
      single-shot laser-induced breakdown spectra. The analyte signal investigated is
      the 288.1-nm Si I emission line provided by an aerosol stream of monodisperse 2.5
      microm-sized silica microspheres. Both the Si emission line and a spectral region
      corresponding to continuum emission are used to evaluate the statistical
      distribution of spectral noise. The probability of false hits is determined by
      evaluating various conditional processing thresholds. As the detection threshold
      increases, the rate of detected silica particle hits decreases along with the
      expected fraction of false-particle hits (i.e., spectral noise). For all
      threshold values the signal-to-noise ratio is found to provide a more robust
      metric for single-shot analyte detection compared with the peak-to-base ratio.

PMID- 14594061
TI  - Analysis by laser-induced breakdown spectroscopy of complex solids, liquids, and
      powders with an echelle spectrometer.
AB  - One of the most promising approaches to laser-induced breakdown spectroscopy
      (LIBS) experiments involves the use of an echelle spectrometer coupled with an
      intensified CCD. Even if drawbacks remain with its use, the echelle spectrometer
      facilitates a multielemental analysis that is more rapid than can be obtained
      with the more-conventional Czerny-Turner spectrometer and, moreover, does not
      sacrifice reliability. Quantitative results obtained with such apparatus for
      solids, liquids, powders, and gases are described and when possible compared with
      results from Czerny-Turner spectrometers. Liquid analysis by LIBS with echelle
      spectrometers has allowed a spectral database to be compiled. Once the
      qualitative spectra of pure elements in aqueous solutions, are obtained, they can
      be used for qualitative analysis of unknown samples.

PMID- 14594062
TI  - Laser-induced plasma spectroscopy to as low as 130 nm when a gas-purged
      spectrograph and ICCD detection are used.
AB  - An experimental setup is described for measuring laser-induced plasma emission
      spectra in the near vacuum UV with a Czerny-Turner spectrograph and intensified
      charge-coupled device under atmospheric pressure. With a simple gas-purge
      technique, emission lines down to 130 nm could be recorded. The strongest
      emission lines of bromine, chlorine, and iodine in the near vacuum UV are easily
      detected.

PMID- 14594063
TI  - Detection of trace elements in liquids by laser-induced breakdown spectroscopy
      with a Meinhard nebulizer.
AB  - The laser-induced breakdown spectroscopy of magnesium, manganese, and chromium
      atoms by use of a commercial Meinhard nebulizer originally designed for
      inductively coupled plasma measurements is described. This is the first time, to
      our knowledge, that this nebulizer has been used for laser-induced breakdown
      spectroscopy measurements. The limit of detection is slightly lower when the
      nebulizer rather than a liquid jet is used in single-pulse laser excitation. In
      addition we present the response characteristics of the nebulizer, such as
      effects of variations in purge gas and liquid flow rate, that are different from
      normal operating specifications. The effects of gate delay, gate width, and laser
      power variations were also studied. The objective of the present research has
      been to consider a new operating mode and conditions in which a better limit of
      detection of trace elements in water can be obtained.

PMID- 14594064
TI  - Double-pulse laser-induced breakdown spectroscopy with liquid jets of different
      thicknesses.
AB  - Double-pulse laser-induced breakdown spectroscopy of magnesium in water has been
      performed with different jet thicknesses. A Meinhard nebulizer has been used to
      create a jet of 0.3-mm diameter, whereas a homemade liquid jet injector produced
      a thicker jet of 1.0-mm diameter. The relationship of line intensity to delay
      time between the two laser pulses for these two jets is compared and discussed.
      The limits of detection in these two jets are also determined and compared. The
      line intensity observed from the double-pulse measurement is correlated with the
      measured electron density calculated with the Halpha line. Also, the behavior of
      plasma density relative to time delay between the lasers is described.

PMID- 14594065
TI  - Supersensitive detection of sodium in water with use of dual-pulse laser-induced
      breakdown spectroscopy.
AB  - Laser-induced breakdown spectroscopy has been used to detect sodium (Na) in
      water. Laser-induced breakdown was formed by dual-pulse and crossed beam Nd:YAG
      lasers on a water film. To improve the detection sensitivity, the fluorescence
      intensity dependence on timing between laser pulses, the delay time of
      fluorescence detection timing, the gate width of fluorescence detection period,
      and the laser energy were investigated. Under the optimized conditions, the
      detection limit of Na in water was achieved in the range of 0.1 parts per
      billion. The developed system is applicable for quick and supersensitive
      detection of Na atoms in water.

PMID- 14594066
TI  - Line-focused laser ablation for depth-profiling analysis of coated and layered
      materials.
AB  - The performance features of line-focused laser ablation for the characterization
      of interfaces in layered materials by laser-induced plasma spectrometry (LIPS)
      have been compared with the point-focusing method in terms of signal precision,
      signal-to-noise ratio, ablation rates, and surface sensitivity. In both optical
      configurations a pulsed Nd:YAG laser beam operating at 532 nm, with a homogeneous
      energy distribution (flattop laser), is used to generate point and microline
      plasmas on the sample surface. Subsequent light from the plasma is spectrally
      resolved and detected with an imaging spectrograph and an intensified charge
      coupled-device detector that is binned along the slit-height direction. Line
      focusing LIPS permits much higher laser power input while maintaining relatively
      low laser fluence, thus yielding better surface sensitivity and improved
      detection power. Values of the signal-to-noise ratio are improved by a factor of
      6. In addition the ablation rate is 9 nm/pulse with the microline approach
      compared with 23 nm/pulse obtained with the point-focusing method. The results
      demonstrate that the microline-focusing approach is suitable for the depth
      analysis of coated and layered materials.

PMID- 14594067
TI  - Micro-laser-induced breakdown spectroscopy technique: a powerful method for
      performing quantitative surface mapping on conductive and nonconductive samples.
AB  - Laser-induced breakdown spectroscopy (LIBS) has been applied mainly to bulk
      analysis of solids, liquids, and gases and less frequently for elemental
      microanalysis of solid surfaces. A micro-LIBS device devoted to analysis of the
      distribution of elements on surfaces is described. This device offers rapid
      access with a 3-microm spatial resolution to the microchemical structures of both
      conductive and nonconductive samples. Quantitative microchemical results of
      applications to ceramics are reported. By the use of a time-resolved acquisition
      spectrum, cerium in a uranium matrix was characterized with a cerium detection
      limit of 1.14%. Calibration curves obtained with manipulations during 1 year
      facilitated evaluations of reproducibility and repeatability. A 2% single-shot
      repeatability with a calibration reproducibility of approximately 7% is reported.

PMID- 14594068
TI  - Geiger photodiode array for compact, lightweight laser-induced breakdown
      spectroscopy instrumentation.
AB  - The development of a unique spectrometer based on an array of Geiger photodiodes
      has been shown to enhance the performance of laser-induced breakdown spectroscopy
      (LIBS) instrumentation. These compact, silicon-based detectors eliminate the need
      for postamplification electronics, allow for the detection of single photons at
      room temperature, and do not require complex gating-timing circuitry. The
      detectors have dark-count rates of <500 Hz at room temperature and a good
      response from the UV to the near IR. Their high sensitivity makes them candidates
      for standoff analysis as part of a LIBS spectrum analyzer.

PMID- 14594069
TI  - Spectral analysis of the acoustic emission of laser-produced plasmas.
AB  - A Q-switched frequency Nd:YAG laser was focused on copper, aluminum, and lead
      targets. The acoustic emission accompanying plasma formation was acquired and
      analyzed in both the time and the frequency domains. Spectral analysis of the
      shock wave has proved to be a simple and low-cost diagnostic of plasma phenomena.
      In the time domain, several propagation mechanisms of the shock wave were
      observed and the velocity profile of the shock wave estimated. Spectral
      measurements were performed in the acoustic propagation regime of the shock
      waves. Spectral features related to the plasma formation mechanism were
      identified and discussed for copper, aluminum, and lead on the basis of the
      physical properties of these elements, the expansion mechanisms of the plasma,
      and an empirical parameter representative of the transported energy.

PMID- 14594070
TI  - Dual-pulse laser-induced breakdown spectroscopy in bulk aqueous solution with an
      orthogonal beam geometry.
AB  - Use of dual-pulse laser-induced breakdown spectroscopy with an orthogonal spark
      orientation is presented as a technique for trace metal analysis in bulk aqueous
      solutions. Two separate Q-switched Nd:YAG lasers operating at their fundamental
      wavelengths are used to form a subsurface, laser-induced plasma in a bulk aqueous
      solution that is spectroscopically analyzed for the in situ detection of Ca, Cr,
      and Zn. Optimizing the key experimental parameters of proper spark alignment,
      gate delay (td), gate width (tb), and interpulse timing (deltaT) allowed
      experimentally determined detection limits of the order of micrograms per
      milliliter and submicrograms per milliliter. We present supporting evidence of a
      sampling mechanism that involves the formation of a cavitation bubble with the
      first pulse (E1) followed by analysis of that bubble with a second pulse (E2).
      The plasma created by E2 contains the analytically relevant information from the
      aqueous sample and often represents >250-fold enhancement over a single laser
      pulse with energy equal to E1 alone.

PMID- 14594071
TI  - Comparative study of two new commercial echelle spectrometers equipped with
      intensified CCD for analysis of laser-induced breakdown spectroscopy.
AB  - The purpose of this paper is to provide the reader with comparative information
      about two new commercial echelle spectrometers equipped with intensified CCD
      (ICCD) detectors for laser-induced breakdown spectroscopy analysis. We carried
      out a performance comparison between two commercial ICCD/echelle spectrometers
      [ESA 3000 (LLA Instruments GmbH, Berlin-Adlershof, Germany) and a Mechelle 7500
      (Multichannel Instruments, Stockholm, Sweden)] for the determination of the
      concentrations of Be, Mg, Si, Mn, Fe, and Cu in the same Al alloy samples
      adopting the same experimental conditions. The results show that both systems,
      despite their differences in terms of resolution, have similar performance in
      terms of sensitivity and precision of measurements for these elements in an Al
      alloy matrix at least for the range of wavelength 280-400 nm studied in this
      work.

PMID- 14594072
TI  - Dual-pulse laser-induced breakdown spectroscopy with combinations of femtosecond
      and nanosecond laser pulses.
AB  - Nanosecond and femtosecond laser pulses were combined in an orthogonal
      preablation spark dual-pulse laser-induced breakdown spectroscopy (LIBS)
      configuration. Even without full optimization of interpulse alignment, ablation
      focus, large signal, signal-to-noise ratio, and signal-to-background ratio
      enhancements were observed for both copper and aluminum targets. Despite the
      preliminary nature of this study, these results have significant implications in
      the attempt to explain the sources of dual-pulse LIBS enhancements.

PMID- 14594073
TI  - Laser-induced breakdown spectroscopy at high temperatures in industrial boilers
      and furnaces.
AB  - Laser-induced breakdown spectroscopy (LIBS) was applied (1) near the superheater
      of an electric power generation boiler burning biomass, coal, or both; (2) at the
      exit of a glass-melting furnace burning natural gas and oxygen; and (3) near the
      nose arches of two paper mill recovery boilers burning black liquor. Difficulties
      associated with the high temperatures and high particle loadings in these
      environments were surmounted by use of novel LIBS probes. Echelle and linear
      spectrometers coupled to intensified CCD cameras were used individually and
      sometimes simultaneously. Elements detected include Na, K, Ca, Mg, C, B, Si, Mn,
      Al, Fe, Rb, Cl, and Ti.

PMID- 14594074
TI  - Single-pollen analysis by laser-induced breakdown spectroscopy and Raman
      microscopy.
AB  - The application of laser-induced breakdown spectroscopy to the analysis of single
      biological microparticles (bioaerosols) is described, exemplified here for a
      range of pollens. Spectra were recorded by exposure of the pollen to a single
      laser pulse from a Nd:YAG laser (lambda = 1064 nm, Ep approximately 30 mJ). The
      intensities of the single-pulse laser-induced breakdown spectra fluctuated
      dramatically, but an internal signal calibration procedure was applied that
      referenced elemental line intensities to the carbon matrix of the sample
      (represented by molecular bands of CN and C2). This procedure allowed us to
      determine relative element concentration distributions for the different types of
      pollen. These pollens exhibited some distinct concentration variations, for both
      major and minor (trace) elements in the biomatrix, through which ultimately
      individual pollens might be identified and classified. The same pollen samples
      were also analyzed by Raman microscopy, which provided molecular compositional
      data (even with spatial resolution). These data allowed us to distinguish between
      biological and nonbiological specimens and to obtain additional classification
      information for the various pollen families, complementing the laser-induced
      breakdown spectroscopy measurement data.

PMID- 14594076
TI  - Spectrochemical microanalysis of aluminum alloys by laser-induced breakdown
      spectroscopy: identification of precipitates.
AB  - Multielemental microanalysis of commercially available aluminum alloys has been
      performed in air by laser-induced breakdown spectroscopy (LIBS) by use of UV
      laser pulses with energies below 10 microJ. It is shown that the LIBS technique
      is capable of detecting the elemental composition of particles less than 10
      microm in size, such as precipitates in an aluminum alloy matrix, by using single
      laser shots. Chemical mapping with a lateral resolution of approximately 10
      microm of the distribution of precipitates in the surface plane of a sample was
      also carried out. Two main types of precipitate, namely, Mn-Fe-Cu (type I) and Mg
      Cu (type II), were unambiguously distinguished in our LIBS experiments, in good
      agreement with x-ray microanalysis measurements. The relative standard deviations
      of emission of the main minor constituent elements (Cu, Mg, Mn) of the aluminum
      2024 alloy range from 33% to 39% when laser shots on the precipitates are
      included in the analysis but decrease to a range from 5.3% to 7.4% when laser
      shots are taken only on the matrix material, excluding the precipitates.

PMID- 14594075
TI  - Application of laser-induced breakdown spectroscopy technique to hair tissue
      mineral analysis.
AB  - The concentration of the main minerals present in human hair is measured on
      several subjects by Calibration-Free Laser-Induced Breakdown Spectroscopy (CF
      LIBS) and compared with the results obtained through a commercial analytical
      laboratory. The possibility of using CF-LIBS for mineral analysis in hair is
      discussed, as well as its feasibility for the fast and inexpensive determination
      of the occurrence of heavy-metal poisoning in hair.

PMID- 14594077
TI  - Laser-induced breakdown spectroscopy analysis of energetic materials.
AB  - A number of energetic materials and explosives have been studied by laser-induced
      breakdown spectroscopy (LIBS). They include black powder, neat explosives such as
      TNT, PETN, HMX, and RDX (in various forms), propellants such as M43 and JA2, and
      military explosives such as C4 and LX-14. Each of these materials gives a unique
      spectrum, and generally the spectra are reproducible shot to shot. We observed
      that the laser-produced microplasma did not initiate any of the energetic
      materials studied. Extensive studies of black powder and its ingredients by use
      of a reference spectral library have demonstrated excellent accuracy for unknown
      identification. Finally, we observed that these nitrogen- and oxygen-rich
      materials yield LIBS spectra in air that have correspondingly different O:N peak
      ratios compared with air. This difference can help in the detection and
      identification of such energetic materials.

PMID- 14594078
TI  - Laser-induced breakdown spectroscopy for the detection of gunshot residues on the
      hands of a shooter.
AB  - Laser-induced breakdown spectroscopy (LIBS) has been used to determine whether
      the hands of a suspected gun user contain traces of gunshot residue. Samples are
      obtained by pressing adhesive tape against the skin of the suspect and analyzing
      the tape directly. When the suspect has fired multiple shots, or if the gun has
      not been cleaned, the gunshot residue provides a spectral signature that is
      readily apparent, but a person who has fired a single shot from a clean gun is
      not so easy to identify. The error rates associated with the LIBS identification
      of a subject who fired one shot from a clean gun have been evaluated by Monte
      Carlo simulation techniques, and criteria are proposed for defining a positive or
      a negative test result.

PMID- 14594079
TI  - Optimal boiler control through real-time monitoring of unburned carbon in fly ash
      by laser-induced breakdown spectroscopy.
AB  - A laser-induced breakdown spectroscopy (LIBS) technique has been applied for
      detection of unburned carbon in fly ash, and an automated LIBS unit has been
      developed and applied in a 1000-MW pulverized-coal-fired power plant for real
      time measurement, specifically of unburned carbon in fly ash. Good agreement was
      found between measurement results from the LIBS method and those from the
      conventional method (Japanese Industrial Standard 8815), with a standard
      deviation of 0.27%. This result confirms that the measurement of unburned carbon
      in fly ash by use of LIBS is sufficiently accurate for boiler control.
      Measurements taken by this apparatus were also integrated into a boiler-control
      system with the objective of achieving optimal and stable combustion. By control
      of the rotating speed of a mill rotary separator relative to measured unburned
      carbon content, it has been demonstrated that boiler control is possible in an
      optimized manner by use of the value of the unburned-carbon content of fly ash.

PMID- 14594080
TI  - Microanalysis of tool steel and glass with laser-induced breakdown spectroscopy.
AB  - A laser microscope system for the microanalytical characterization of complex
      materials is described. The universal measuring principle of laser-induced
      breakdown spectroscopy (LIBS) in combination with echelle optics permits a fast
      simultaneous multielement analysis with a possible spatial resolution below 10
      pm. The developed system features completely UV-transparent optics for the laser
      microscope coupling and the emission beam path and enables parallel signal
      detection within the wavelength range of 200-800 nm with a spectral resolution of
      a few picometers. Investigations of glass defects and tool steels were performed.
      The characterization of a glass defect in a tumbler by a micro-LIBS line scan,
      with use of a 266-nm diode-pumped Nd:YAG laser for excitation, is possible by
      simple comparison of plasma spectra of the defect and the surrounding area.
      Variations in the main elemental composition as well as impurities by trace
      elements are detected at the same time. Through measurement of the calibration
      samples with the known concentration of the corresponding element, a correlation
      between the intensity of spectral lines and the element concentration was also
      achieved. The change of elemental composition at the transient stellite solder of
      tool steels has been determined by an area scan. The two-dimensional pictures
      show abrupt changes of the element distribution along the solder edge and allow
      fundamental researches of dynamic modifications (e.g., diffusion) in steel.

PMID- 14594082
TI  - Shooting slurries with laser-induced breakdown spectroscopy: sampling is the name
      of the game.
AB  - Analyses of iron ore slurries in industrial and laboratory environments showed
      that many physical and geometric parameters affect the stability and
      reproducibility of the response to laser-induced breakdown spectroscopy. A
      thorough reexamination of the sampling strategy led to a revised sampling layout
      that ensures a true representative sampling of the slurry and significantly
      improves the sensitivity and repeatability of the sampling method. An examination
      of the characteristics of slurries revealed that the mean particulate size and
      the concentration of solids in a slurry influence the measurement of silica,
      whereas the magnetite content is responsible for a matrix effect. On-line
      monitoring of iron ore slurries should be practicable, provided that these
      variables are controlled within a few percent or that some means of correction is
      implemented.

PMID- 14594081
TI  - Laser-induced breakdown spectroscopy used to detect palladium and silver metal
      dispersed in bacterial cellulose membranes.
AB  - The technique of laser-induced breakdown spectroscopy has been used for the first
      time to our knowledge for the identification of metals such as palladium and
      silver that were dispersed in bacterial cellulose membranes. These results for
      palladium-dispersed films have been correlated to a calibration curve obtained by
      use of atomic absorption spectroscopy and were found to be in good agreement. The
      experiments were conducted by use of wet and dry metal-doped membranes. The metal
      peaks obtained with a dry membrane are greater than five times higher in signal
      to-background ratio than when metals are detected by a hydrated membrane. The
      advantage of this laser-based technique is that minimal sample handling and
      sample preparation are needed and measurements are completed in real time (a few
      seconds). Hence this technique can be used for the detection of metals in dry
      membranes that would be used in the construction of electrode assemblies.

PMID- 14594083
TI  - Detection of bacteria by time-resolved laser-induced breakdown spectroscopy.
AB  - A laser-induced breakdown spectroscopy technique for analyzing biological matter
      for the detection of biological hazards is investigated. Eight species were
      considered in our experiment: six bacteria and two pollens in pellet form. The
      experimental setup is described, then a cumulative intensity ratio is proposed as
      a quantitative criterion because of its linearity and reproducibility. Time
      resolved laser-induced breakdown spectroscopy (TRELIBS) exhibits a good ability
      to differentiate among all these species, whatever the culture medium, the
      species or the strain. Thus we expect that TRELIBS will be a good candidate for a
      sensor of hazards either on surfaces or in ambient air.

PMID- 14594084
TI  - Measurement and analysis of atomic and diatomic carbon spectra from laser
      ablation of graphite.
AB  - Spectra from plasma produced by laser-induced breakdown of graphite were recorded
      and analyzed to increase our understanding of the way in which carbon
      nanoparticles are created during Nd:YAG laser ablation of graphite. The effects
      of various buffer gases were studied. Electron density and temperature were
      determined from spectra of the first and second ions of atomic carbon. The C2
      Swan spectrum was also prominent in most of the measured spectra. Temperature was
      inferred from each experimental Swan spectrum by determination of the temperature
      for which a synthetic Swan spectrum best fitted, in the least-squares sense, the
      measured spectrum.

PMID- 14594085
TI  - Liquid steel analysis with laser-induced breakdown spectrometry in the vacuum
      ultraviolet.
AB  - Laser-induced breakdown spectrometry (LIBS) with multiple pulse excitation has
      been applied for the multielemental analysis of liquid steel. The laser beam and
      the measuring radiation are guided inside a moveable lance to gain access to the
      melt surface from the top. Low-alloy steel grades were investigated with a focus
      on the light elements phosphorus, sulfur, and carbon by use of emission
      wavelengths in the vacuum ultraviolet. Calibration curves were determined for the
      elements carbon, phosphorus, sulfur, nickel, and chromium in steel melts of 100
      kg. The estimated limits of detection for the light elements phosphorus, sulfur,
      and carbon are below 21 microg/g for direct analysis of liquid steel with LIBS.
      The results demonstrate the potential of the laser-based analysis to fulfill the
      requirements for a process integrated on-line analysis in the secondary
      metallurgy of steel works.

PMID- 14594086
TI  - Laser-induced breakdown spectroscopy of bacterial spores, molds, pollens, and
      protein: initial studies of discrimination potential.
AB  - Laser-induced breakdown spectroscopy (LIBS) has been used to study bacterial
      spores, molds, pollens, and proteins. Biosamples were prepared and deposited onto
      porous silver substrates. LIBS data from the individual laser shots were analyzed
      by principal-components analysis and were found to contain adequate information
      to afford discrimination among the different biomaterials. Additional
      discrimination within the three bacilli studied appears feasible.

PMID- 14594087
TI  - On-line detection of heavy metals and brominated flame retardants in technical
      polymers with laser-induced breakdown spectrometry.
AB  - The use of laser-induced breakdown spectrometry (LIBS) for the analysis of heavy
      metals and brominated flame retardants in end-of-life waste electric and
      electronic equipment (EOL-WEEE) pieces is investigated. Single- and double-pulse
      plasma excitation as well as the influence of detection parameters is studied to
      yield a parameter field with improved sensitivity and limits of detection. A LIBS
      analyzer was set up as an on-line measuring unit to detect heavy metals and
      brominated flame retardants in moving EOL-WEEE pieces in an automatic sorting
      line. An autofocusing unit with an adjustment range of 50 mm was incorporated to
      permit measurements of objects that pass by a LIBS analyzer with their surfaces
      at various distances from it. Tests with EOL-WEEE monitor housings on the
      conveyor belt of a pilot sorting system successfully demonstrated the capability
      of the LIBS analyzer to quantify the concentration of hazardous elements in real
      waste EOL-WEEE pieces.

PMID- 14594088
TI  - Laser-induced breakdown spectroscopy of gas mixtures of air, CO2, N2, and C3H8
      for simultaneous C, H, O, and N measurement.
AB  - Laser-induced breakdown spectroscopy (LIBS) was applied for simultaneous
      measurement of the elements C, H, N, and O in CO2-air, C3H8-CO2, and C3H8-N2 gas
      mixtures at atmospheric pressure. A single 7-mm-diameter aperture at the sample
      chamber was used for 1064-nm Nd:YAG laser irradiation and plasma signal output to
      an echelle spectrometer. Double-pulse laser bursts of approximately 8-ns pulse
      width (FWHM) and 250-ns interpulse separation were applied to increase the plasma
      signal. Calibration curves of the LIBS signal versus the partial pressure or the
      atomic abundance ratios were taken by dilution series in intervals that are
      relevant in the combustion of heptane (C7H16) near an equivalence ratio of 1.

PMID- 14594089
TI  - Call to action. Enhancing dementia care in family medicine.

PMID- 14594090
TI  - Strengthening research through WONCA. Filling a tall order.

PMID- 14594091
TI  - What about prostate cancer?

PMID- 14594092
TI  - "Timely communication" needs redefining.

PMID- 14594093
TI  - Loss of innocence.

PMID- 14594094
TI  - Taking bisphosphonates during pregnancy.
AB  - QUESTION: Several of my female patients take bisphosphonates for low bone mineral
      density (BMD). Two of them are of reproductive age. Are these drugs safe during
      pregnancy? ANSWER: Very little is currently known about the effects of
      bisphosphonates on human pregnancy. There have been only two reports of
      bisphosphonate use during late pregnancy. Animal studies suggest that
      biphosphonates cross the placenta and that the effect is an extension of the
      expected pharmacologic effect of bisphosphonates on both fetus and mother. Risks
      and benefits should be carefully weighed.

PMID- 14594095
TI  - Ophthaproblem. Optic neuritis.

PMID- 14594096
TI  - Waist circumference and cardiovascular risk.

PMID- 14594097
TI  - High-dose riboflavin for prophylaxis of migraine.

PMID- 14594098
TI  - Sad but true: your father has dementia. An approach to announcing the diagnosis.
AB  - OBJECTIVE: To show that family physicians have an important role in caring for
      patients recently diagnosed with dementia. SOURCES OF INFORMATION: This article
      is based on the authors' clinical experience and on the recommendations of the
      Canadian Consensus Conference on Dementia. MAIN MESSAGE: The authors touch on
      themes often ignored in the literature, such as issues surrounding the first time
      patients and their families are confronted with a diagnosis of dementia. We show
      the advantages of informing patients of the diagnosis and refute arguments for
      keeping it a secret. We then describe aspects of anticipatory counseling, which
      should begin as soon as the diagnosis is made: natural evolution of the disease,
      risk factors, power of attorney, driving, medical follow up, risks of
      polypharmacy, resources for psychological support of caregivers, and orientation
      to community resources (for helping patients remain at home). CONCLUSION:
      Physicians must inform patients and their families of a diagnosis of dementia and
      provide anticipatory counseling so that families can prepare for the long-term
      responsibility of caring for someone with this disease.

PMID- 14594099
TI  - Dementia with Lewy bodies. Review of diagnosis and pharmacologic management.
AB  - OBJECTIVE: To review clinical features of dementia with Lewy bodies (DLB) and to
      guide family physicians in pharmacologic management, including medications to
      avoid. QUALITY OF EVIDENCE A MEDLINE: search of literature from 1995 to 2002 used
      the MeSH terms dementia with Lewy bodies/diagnosis, dementia with Lewy
      bodies/therapy, and antipsychotics/dementia with Lewy bodies. Level II and III
      evidence was available for diagnosis and treatment of DLB. One randomized
      controlled trial of rivastigmine was reviewed and appraised. MAIN MESSAGE:
      Dementia with Lewy bodies is common. Diagnosis can be made by family physicians
      using clinical criteria including presence of dementia with marked fluctuation in
      performance, hallucinations, and the onset of parkinsonism. Cholinesterase
      inhibitors should be considered for neuropsychiatric symptoms. Levodopa-carbidopa
      combinations should be considered for treatment of parkinsonism. Neuroleptics
      should be used with caution because of the risk of serious sensitivity reactions.
      If they are needed, atypical agents could be safer. CONCLUSION: Recognition and
      diagnosis of DLB is important to optimize pharmacologic management and to
      minimize risk of adverse reactions to neuroleptics.

PMID- 14594100
TI  - Universal influenza immunization. Were Ontario family physicians prepared?
AB  - OBJECTIVE: To explore family physicians' experiences during the first year of
      Ontario's universal influenza immunization program. DESIGN: Qualitative study
      using in-depth interviews. SETTING: Thames Valley region of southwestern Ontario.
      PARTICIPANTS: A maximum variation sample of nine family physicians selected by
      snowball sampling after initial consultation with a local family physician
      advisory committee. METHOD: Interviews were audiotaped and transcribed verbatim.
      Analysis was sequential, using a combination of editing, immersion, and
      crystallization. Interview transcripts were read by individual members of the
      team who met to compare findings at several stages during data collection. MAIN
      FINDINGS: The program affected family physicians because immunization strategies
      designed for immunizing high-risk patients needed to be modified to deal with
      greater numbers of patients. While generally supportive of the program,
      physicians found it difficult to implement. Responses reflected ongoing conflict
      between individual and public health priorities, particularly regarding children
      and pregnant women. CONCLUSION: The program could have been more effective if the
      culture and climate of Ontario family practice had been considered during its
      development and implementation.

PMID- 14594101
TI  - Markers of loss of control of hypertension.
AB  - OBJECTIVE: To identify markers for loss of control of hypertension. DESIGN:
      Questionnaire administered to patients who had been monitored for 18 months and
      had had their blood pressure (BP) measured many times. SETTING: Fifty family
      practices in southeastern Ontario. PARTICIPANTS: Three hundred eighty-five adults
      with essential hypertension that was initially stable and controlled by
      medication. MAIN OUTCOME MEASURES: Change in BP (from baseline to mean of three
      measurements over 18 months) and proportion of patients with BP exceeding
      threshold values at most follow-up visits. RESULTS: Higher income was associated
      with an increase in diastolic BP; poor adherence to medication regimens and
      higher life stress were associated with increases in systolic BP Stress also led
      to a twofold increase in risk of exceeding BP thresholds. Other factors under
      study were not related to loss of control. CONCLUSION: Adherence to medication
      regimens, higher income, and life stress were the only factors associated with
      elevated BP or loss of control in previously controlled hypertension.

PMID- 14594103
TI  - Gaps in mental health services for seniors.

PMID- 14594102
TI  - Prenatal HIV tests. Routine testing or informed choice?
AB  - OBJECTIVE: To examine how prenatal care providers responded to a new provincial
      policy of offering HIV testing to all prenatal patients, and to determine factors
      associated with self-reported high testing rates. DESIGN: Cross-sectional mailed
      survey. SETTING: Outpatient practices in three Ontario health-planning regions.
      PARTICIPANTS: Prenatal care providers: 784 family physicians, 200 obstetricians,
      and 103 midwives were sent questionnaires and were eligible to participate. MAIN
      OUTCOME MEASURES: Self-reported testing of 80% or more prenatal patients ("high
      testers") and associated practice characteristics, attitudes, and counseling
      practices. RESULTS: Response rate was 57% (622/1087): 43% of respondents were
      high testers. Family physicians were most likely and midwives least likely to be
      high testers. High testers tended to report that they had adequate knowledge of
      HIV testing, that HIV risk among their patients warranted testing all of them,
      and that testing should be routine. Encouraging women to test and not providing
      written information or choice were independently associated with high testing
      rates. CONCLUSION: Strongest predictors of high prenatal HIV testing rates were
      attitudes and practices that favoured a routine approach to testing and that
      placed little emphasis on informed consent.

PMID- 14594104
TI  - Modeling interindividual variation in physiological factors used in PBPK models
      of humans.
AB  - Modeling interindividual variation in internal doses in humans using PBPK models
      requires data on the variation in physiological parameters across the population
      of interest. These data should also reflect the correlations between the values
      of the various parameters in a person. In this project, we develop a source of
      data for human physiological parameters where (1) the parameter values for an
      individual are correlated with one another, and (2) values of parameters capture
      interindividual variation in populations of a specific gender, race, and age
      range. The parameters investigated in this project include: (1) volumes of
      selected organs and tissues; (2) blood flows for the organs and tissues; and (3)
      the total cardiac output under resting conditions and average daily inhalation
      rate. These parameters are expressed as records of correlated values for the
      approximately 30,000 individuals evaluated in the NHANES III survey. A computer
      program, Physiological Parameters for PBPK Modeling (P3M), is developed that
      allows records to be retrieved randomly from the database with specification of
      constraints on age, sex, and ethnicity. P3M is publicly available. The database
      and accompanying software provide a convenient tool for parameterizating models
      of interindividual variation in human pharmacokinetics.

PMID- 14594105
TI  - The benchmark dose method--review of available models, and recommendations for
      application in health risk assessment.
AB  - The benchmark dose method has been proposed as an alternative to the no-observed
      adverse-effect level (NOAEL) approach for assessing noncancer risks associated
      with hazardous compounds. The benchmark dose method is a more powerful
      statistical tool than the traditional NOAEL approach and represents a step in the
      right direction for a more accurate risk assessment. The benchmark dose method
      involves fitting a mathematical model to all the dose-response data within a
      study, and thus more biological information is incorporated in the resulting
      estimates of guidance values (e.g., acceptable daily intakes, ADIs). Although
      there is an increasing interest in the benchmark dose approach, it has not yet
      found its way into the regulatory toxicology in Europe, while in the United
      States the U.S. Environmental Protection Agency (EPA) already uses the benchmark
      dose in health risk assessment. Several software packages are today available for
      benchmark dose calculations. The availability of software to facilitate the
      analysis can make modeling appear simple, but often the interpretation of the
      results is not trivial, and it is recommended that benchmark dose modeling be
      performed in collaboration with a toxicologist and someone familiar with this
      type of statistical analysis. The procedure does not replace expert judgments of
      toxicologists and others addressing the hazard characterization issues in risk
      assessment. The aim of this article is to make risk assessors familiar with the
      concept, to show how the method can be used, and to describe some possibilities,
      limitations, and extensions of the benchmark dose approach. In this article the
      benchmark dose approach is presented in detail and compared to the traditional
      NOAEL approach. Statistical methods essential for the benchmark dose method are
      presented in Appendix A, and different mathematical models used in the U.S. EPA's
      BMD software, the Crump software, and the Kalliomaa software are described in the
      text and in Appendix B. For replacement of NOAEL in health risk assessment it is
      considered important that consensus is reached on the crucial parts of the
      benchmark dose method, that is, selection of risk types and the determination of
      a response level corresponding to the BMD, especially for continuous data. It is
      suggested that the BMD method is used as a first choice and that in cases where
      it is not possible to fit a model to the data the traditional NOAEL approach
      should be used instead. The possibilities to make benchmark dose calculations on
      continuous data need to be further investigated. In addition, it is of importance
      to study whether it would be appropriate to increase the number of dose levels by
      decreasing the number of animals in each dose group.

PMID- 14594106
TI  - Potential human cancer risks from exposure to PCBs: a tale of two evaluations.
AB  - In 1999 the Agency for Toxic Substances and Disease Registry (ATSDR) released a
      Draft Toxicological Profile for Polychlorinated Biphenyls (PCBs). In reviewing
      the potential human carcinogenicity of PCBs, ATSDR (1999) concluded that "The
      weight of evidence does not support a causal association for PCBs and human
      cancer at this time." Just 1 year later, in an updated Toxicological Profile for
      Polychlorinated Biphenyls (PCBs), the conclusions of another analysis (ATSDR,
      2000) on whether exposure to PCBs might represent a carcinogenic risk to humans
      had dramatically changed to "Overall, the human studies provide some evidence
      that PCBs are carcinogenic" and "some of these studies provide meaningful
      evidence that PCBs are carcinogenic in humans." Because this is a substantially
      different conclusion than that reached only one year previously, it raises a
      number of questions that must be considered particularly since "weight of
      evidence" has a precise meaning in the context of evaluating a body of
      epidemiological data. The present review addresses the additional scientific data
      that became available between the ATSDR 1999 and 2000 evaluations that was of a
      magnitude to offset the weight of evidence from numerous epidemiological studies
      that exposure to PCBs was not causally associated with human cancer to a
      conclusion only 1 year later that there was now "meaningful evidence" that PCBs
      posed a carcinogenic risk to humans. Also of interest are the criteria upon which
      this conclusion is based and the distinction between "weight of evidence" and the
      newer descriptors of "some evidence" and "meaningful evidence." However, as shown
      in this review, only one relevant study was published between the ATSDR 1999 and
      2000 evaluations and the results of this study were unequivocally supportive of
      the 1999 conclusion. Because of the continuing controversy surrounding this
      issue, in this review, all relevant epidemiological data on PCBs are summarized
      and subjected to another weight of evidence evaluation. This critical review is
      based on the most recent guidelines (U.S. EPA, 1999a, 2003) for conducting weight
      of-evidence evaluations on a body of epidemiological data. Applying a weight-of
      evidence evaluation to the PCB epidemiological studies can only lead to the
      conclusion that there is no causal relationship between PCB exposure and any form
      of cancer, thereby confirming the conclusions of ATSDR (1999). Also considered is
      the methodology and logic used by ATSDR (2000) that resulted in overturning the
      weight of evidence conclusions concerning the human carcinogenicity of PCBs in
      ATSDR (1999). This issue may have public health and policy implications. It seems
      appropriate that unbiased evaluations of a body of data, even of controversial
      issues such as the potential human carcinogenicity of PCBs, be conducted in a
      transparent manner following applicable guidelines. The dramatic differences
      between the conclusions of ATSDR (1999) and ATSDR (2000) do not appear to be
      consistent with this process.

PMID- 14594107
TI  - Effects of cortistatin-14 and somatostatin-14 on the endocrine response to
      hexarelin in humans.
AB  - Cortistatin (CST)-14, a neuropeptide with high structural homology with
      somatostatine (SS)-14, binds all SS receptor subtypes but also shows activities
      not shared by SS. CST and SS are often co-expressed in the same neurons but are
      regulated by different stimuli. Moreover, CST, but not SS, also binds the GH
      secretagogue (GHS) receptor. We compared the effects of CST-14 and SS-14 (2.0
      microg/kg/h i.v. from -30 to +90 min) on the endocrine response to hexarelin
      (HEX, 1.0 microg/kg i.v. at 0 min), a synthetic GHS, in 6 normal volunteers [age
      (mean+/-SEM): 28.7+/-2.9 yr; body mass index: 23.4+/-0.8 kg/m2]. GH, PRL, ACTH,
      cortisol, insulin and glucose levels were measured at each time point. CST-14
      inhibited spontaneous GH secretion [delta-areas under curves (-AUC): -83.57+/
      44.8 vs 2.3+/-2.7 microg/l/h, p<0.01] to the same extent of SS-14 (-186.1+/-162.9
      microg/l/h, p<0.01). CST-14 as well as SS-14 also inhibited insulin secretion
      (p<0.05). The GH response to HEX was similarly inhibited by either CST-14 (AUC:
      3814.1+/-924.2 vs 1212.9+/-379.8 microg/l/h, p<0.05) or SS-14 (720.9+/-158.6
      microg/l/h, p<0.05). HEX significantly increased PRL, ACTH and cortisol levels
      but these responses were not modified by either CST-14 or SS-14. The effects of
      CST-14 and SS-14 on insulin and glucose levels were not modified by HEX. In
      conclusion, this study shows that CST-14 inhibits the GH response to HEX to the
      same extent of SS-14. Like SS-14, CST-14 also inhibits insulin secretion but both
      do not modify the stimulatory effects of HEX on lactotroph and corticotroph
      secretion. Thus, CST-14 exerts full SS-14 activity in humans.

PMID- 14594108
TI  - Identification of two novel mutations in the human growth hormone receptor gene.
AB  - Deletions and mutations in the growth hormone receptor gene are the underlying
      etiology of Laron syndrome (LS). Most of the patients are distributed in and
      originating from the Mediterranean and Middle-Eastern countries. Thirty-nine
      mutations have been described so far. We hereby report 2 novel nonsense
      mutations, one in exon 2 found in three Jewish-Iraqi patients from Israel; and
      another in exon 6 found in an Italian girl. DNA sequencing of exon 2 revealed a G
      to A transition at nucleotide 83 in the fourth codon of the signal peptide (W
      15X). In exon 6, a T to A transversion was found in amino acid 141 (L141X). Both
      mutations introduced a premature termination codon that led to a truncated non
      functioning receptor. In addition we found in the Jewish-Iraqi patients, a
      mutation in exon 7 (R211H, previously described) and in the Italian family the
      polymorphism Gly168, in exon 6.

PMID- 14594109
TI  - The midnight-to-morning urinary cortisol increment method is not reliable for the
      assessment of hypothalamic-pituitary-adrenal insufficiency in patients with end
      stage kidney disease.
AB  - A previous study reported that the midnight-to-morning urinary cortisol increment
      method could be used to reliably assess the insufficiency of the hypothalamic
      pituitary-adrenal (HPA) axis. The principal aim of the present study is to verify
      whether the midnight-to-morning urinary cortisol increment is a reliable method
      for the assessment of the HPA axis in patients with various degrees of impaired
      kidney function. Fifty-six clinically stable patients with chronic kidney disease
      (CKD) and 14 healthy subjects were enrolled in the present study. Patients with
      CKD were divided on the basis of glomerular filtration rate (GFR) into the
      following arbitrary groups: mild (GFR: 60-89 ml/min/1.73 m2, no.=15), moderate
      (GFR: 30-59 ml/min/1.73 m2, no.=12) and severe kidney insufficiency (GFR: 15-29
      ml/min/1.73 m2, no.=13), and hemodialysis patients. Plasma cortisol and ACTH
      levels were measured. The HPA axis was assessed by short Synacthen test and
      overnight dexamethasone suppression test. Double voided urine samples were
      collected at midnight and waking in the patients and the controls. Urinary free
      cortisol (UFC) and creatinine levels were measured and the UFC/creatinine ratio
      (Cort/Cr) was calculated. Then, the Cort/Cr increment was calculated as the
      morning Cort/Cr minus the midnight Cort/Cr. Baseline plasma cortisol levels were
      not significantly different between two groups. However, we found that CKD
      patients had significantly greater plasma ACTH levels than controls. The patients
      with CKD had also significantly lower morning UFC levels than controls and there
      was a progressive fall in morning UFC levels with decreasing GFR. The assessment
      of the HPA axis in patients with GFR lower than 29 ml/min was hampered by falsely
      abnormal responses to the midnight-to-morning urinary cortisol increment method.
      Plasma cortisol responded normally to exogenously administered ACTH, while plasma
      cortisol was suppressed by overnight dexamethasone administration in all patients
      with CKD. In conclusion, this method is not a reliable test for assessment of the
      HPA insufficiency in patients with GFR lower than 29 ml/min.

PMID- 14594110
TI  - Rise in morning saliva cortisol is associated with abdominal obesity in men: a
      preliminary report.
AB  - An abnormal regulation of the hypothalamic-pituitary-adrenal (HPA) axis is
      associated with risk factors for cardiovascular disease and Type 2 diabetes
      mellitus. The objective of this study was to examine if morning saliva cortisols
      show similar associations. Twenty-eight men, all 53 yr of age, delivered during
      an ordinary working day saliva cortisol samples immediately upon awakening and 15
      min thereafter as well as at different times during the day, including after a
      standardized lunch. Dexamethasone (0.5 mg) suppression of cortisol was also
      measured. The rise of morning cortisol values was positively associated with body
      mass index (r: 0.45, p=0.016), waist/hip ratio (r: 0.54, p=0.003), abdominal
      sagittal diameter (r: 0.54, p=0.003), glucose (r: 0.54, p=0.003), insulin (r:
      0.57, p=0.002) and triglycerides (r: 0.46, p=0.014). The morning rise also
      correlated positively with the elevation of cortisol following lunch (r: 0.45,
      p=0.043) but not with other cortisol measurements or dexamethasone suppression.
      Elevation of cortisol immediately after awakening has previously been found to
      provide a simple indicator of HPA axis regulation, as suggested also by the
      results of this study, and an elevated rise has been reported after exposure to
      frequent or chronic perceived stress. The rise of cortisol immediately after
      awakening might be an indicator of an increased risk of developing serious,
      prevalent diseases via the metabolic syndrome.

PMID- 14594111
TI  - The methylenetethrahydrofolate reductase (MTHFR) C677T polymorphism and male
      infertility in Italy.
AB  - The 677T allele of the MTHFR gene has been suggested to represent a factor of
      risk for male infertility. In order to confirm this association, we investigated
      the presence of the 677T allele in 93 Italian infertile patients, selected after
      the exclusion of other possible genetic causes of infertility, and in 105 Italian
      fertile controls. The homozygous 677TT genotype was present in 20.4% of patients
      and 27.6% of controls. These results do not support an association between the
      MTHFR 677T allele and male infertility in Italy.

PMID- 14594112
TI  - Growth hormone secretion in polytransfused prepubertal patients with homozygous
      beta-thalassemia. Effect of long-term recombinant GH (recGH) therapy.
AB  - Growth was monitored in 133 male and 150 female North Sardinian prepubertal
      patients with homozygous beta-thalassemia in order to ascertain the incidence of
      GH deficiency (GHD) and the effects of long-term recombinant GH (recGH) treatment
      on growth velocity and bone maturation. A significant reduction in growth
      velocity and a fall in IGF-I levels was observed in 19 male and 16 female
      patients (12.3%). Their peak GH responses to GHRH (5.45+/-0.78 and 4.99+/-0.86
      ng/ml) and clonidine administration (4.21+/-0.32 and 4.15+/-0.27 ng/ml in males
      and females, respectively) were markedly reduced with respect to control subjects
      (p<0.01). No statistically significant correlation was found between
      chronological age, number of blood units received, plasma ferritin levels and
      plasma IGF-I levels as well as with peak GH response to stimulation. Thalassemic
      patients with GHD had plasma ferritin levels (1382.44+/-160.34 and 1255.23+/
      139.81 ng/ml in males and females, respectively) significantly lower than those
      recorded in the other patients (2848.94+/-283.61 and 3077.82+/-220.51 ng/ml).
      Patients with GHD were treated with recGH for an average period of 59 months
      (range 26-124). Treatment was able to restore growth and to increase
      significantly plasma IGF-I levels. Growth velocity at the end of the first yr of
      treatment was 6.78+/-1.21 and 6.11+/-0.85 cm/yr in males and females,
      respectively. Growth velocity values and plasma IGF-I levels remained
      significantly higher than basal values throughout the period of treatment.
      However, treatment was unable to normalize bone maturation since bone age values
      were always reduced with respect to chronological age. No incidence of side
      effects was observed. These data indicate that GHD, when present, is one but not
      the sole cause of delayed bone maturation and height deficiency in thalassemia.

PMID- 14594113
TI  - Anti-androgen treatment increases circulating ghrelin levels in obese women with
      polycystic ovary syndrome.
AB  - In a previous study we were the first to describe a negative correlation between
      circulating ghrelin concentrations and androgen levels in human plasma,
      suggesting an interaction between ghrelin and the endocrine regulation of
      reproductive physiology. We now investigated a potential direct regulatory
      influence of circulating androgens on plasma ghrelin levels. Fourteen obese women
      with polycystic ovary syndrome (PCOS) on a hypocaloric diet were randomly
      assigned to treatment groups (open-labeled design), receiving either placebo
      (no.=7) or the antiandrogen flutamide (no.=7) for 6 months. Anthropometry,
      visceral (VAT) and subcutaneous (SAT) adipose tissue (quantified by computerized
      tomography), plasma hormone levels, insulin sensitivity indexes (Quantitative
      Insulin-Sensitivity Check Index-QUICKI) and Homeostatic Model Assessment applied
      to the oral glucose tolerance test (HOMA(OGTT)) were evaluated at baseline and at
      the end of the study. Body weight decreased and insulin resistance indexes
      improved in both groups. A tendency toward a greater loss of VAT was observed in
      the flutamide group. Only in the flutamide group was a significant reduction of
      androgens levels observed. Plasma ghrelin levels significantly increased
      following treatment with flutamide, while ghrelin remained unchanged in the
      placebo group. We observed a negative correlation between changes of ghrelin
      levels and changes of androgen plasma concentration in the flutamide-treated
      group. In the same group a positive correlation was found between plasma ghrelin
      changes and insulin sensitivity as expressed by HOMA(OGTT). Analysis in a
      multiple regression model, however, showed that plasma ghrelin changes were
      mainly due to changes of androgen levels rather than improved insulin
      sensitivity. We, therefore, conclude that androgens are independent modulators of
      circulating ghrelin concentrations.

PMID- 14594114
TI  - Thyroid color flow doppler sonography and radioiodine uptake in 55 consecutive
      patients with amiodarone-induced thyrotoxicosis.
AB  - Amiodarone-induced thyrotoxicosis (AMT) is a life-threatening condition, the
      appropriate management of which is achieved by identifying its different
      subtypes. Type 1 AIT develops in patients with underlying thyroid abnormalities
      and is believed to be due to increased thyroid hormone synthesis and release;
      Type 2 AIT occurs in patients with a normal thyroid gland and is an amiodarone
      induced destructive process of the thyroid. Management differs in the two forms
      of AIT, since Type 1 usually responds to combined thionamides and potassium
      perchlorate therapy, while Type 2 is generally responsive to glucocorticoids.
      Mixed forms, characterized by coexistence of excess thyroid hormone synthesis and
      destructive phenomena, may require a combination of the two therapeutic regimens.
      In this cross-sectional prospective study, 55 consecutive untreated patients,
      whose AIT was subtyped according to clinical and biochemical criteria, were
      evaluated to assess the specificity of color flow doppler sonography (CFDS) and
      thyroidal radioiodine uptake (RAIU) in the differential diagnosis of AIT. Sixteen
      patients (6 men, 10 women, age 66+/-13 yr), who had diffuse or nodular goiter
      with or without circulating thyroid autoantibodies, were classified as Type 1
      AIT; 39 patients (27 men, 12 women, age 65+/-13 yr) with apparently normal
      thyroids were classified as Type 2 AIT. All Type 1 patients had normal or
      increased thyroidal vascularity on CFDS, while Type 2 AIT patients had absent
      vascularity (p<0.0001). Thirteen Type 1 AIT patients had inappropriately normal
      or elevated thyroidal 3-h and 24-h RAIU values (range 6-37% and 10-58%,
      respectively), in spite of elevated values of urinary iodine excretion; the
      remaining 3 patients (two with nodular goiter, one with a thyroid adenoma) had
      low 3-h and 24-h RAIU values (range 1.1-3.0% and 0.9-4.0%, respectively). The
      latter patients, who were unresponsive to the combination of methimazole and
      potassium perchlorate, became euthyroid after the addition of glucocorticoids.
      Thirty-eight Type 2 AIT patients had low 3-h and 24-h RAIU values (range 0.4-3.7%
      and 0.2-3.0%, respectively), but one had inappropriately normal 3-h and 24-h RAIU
      values (6% and 13%, respectively). In conclusion, CFDS can accurately distinguish
      between Type 1 and Type 2 AIT, and in general the CFDS pattern is concordant with
      the thyroid RAIU. However, in 4 out of 55 patients (7%) the thyroid RAIU was
      discrepant, probably reflecting the coexistence of Type 1 and Type 2 AIT. Thus,
      assessment of both CFDS and RAIU may provide a more accurate subtyping of AIT and
      help in selecting the appropriate therapy. Finally, in long standing iodine
      sufficient areas, such as the United States, where the thyroid RAIU is
      consistently low irrespective of the etiology of the AIT, CFDS offers a rapid and
      available method to differentiate between Type 1 and Type 2 AIT.

PMID- 14594115
TI  - Human placenta and fetal membranes express follistatin-related gene mRNA and
      protein.
AB  - Activin A is a placental glycoprotein and possible biological actions during
      pregnancy, suggested by experimental data, are the modulation of cytotrophoblast
      differentiation, placental hormonogenesis and uterotonins secretion. Follistatin
      related gene (FLRG) is a 70 amino acids protein which binds activin A with high
      affinity, and which modulates its biological effects on target tissues by
      preventing the activin A interaction with its receptors. The present study
      investigated whether trophoblast, decidua and fetal membranes express FLRG mRNA
      (by RT-PCR) and peptide (by immunohistochemistry). Tissue specimens were
      collected at first and third trimester of pregnancy, from patients undergoing
      voluntary pregnancy interruption (no.=6; from 8 to 12 gestational weeks) and
      elective caesarean section at term (no.=6; 39-40 weeks of pregnancy). FLRG mRNA
      was expressed by the various gestational tissues both at early gestation and at
      term pregnancy. Immunoreactive protein was found in the trophoblast cells,
      epithelial amniotic and chorionic cells and maternal decidua; nevertheless, the
      most intense FLRG stain was detected in the walls of decidual and placental blood
      vessels. In conclusion, FLRG mRNA and peptide are expressed by placenta and fetal
      membranes. Its different immunolocalization with respect to follistatin and
      activin A supports a different role for FLRG in modulating activin A actions into
      gestational tissues.

PMID- 14594116
TI  - Effect of licorice on the reduction of body fat mass in healthy subjects.
AB  - The history of licorice, as a medicinal plant, is very old and has been used in
      many societies throughout the millennia. The active principle, glycyrrhetinic
      acid, is responsible for sodium retention and hypertension, which is the most
      common side-effect. We show an effect of licorice in reducing body fat mass. We
      studied 15 normal-weight subjects (7 males, age 22-26 yr, and 8 females, age 21
      26 yr), who consumed for 2 months 3.5 g a day of a commercial preparation of
      licorice. Body fat mass (BFM, expressed as percentage of total body weight, by
      skinfold thickness and by bioelectrical impedance analysis, BIA) and
      extracellular water (ECW, percentage of total body water, by BIA) were measured.
      Body mass index (BMI) did not change. ECW increased (males: 41.8+/-2.0 before vs
      47.0+/-2.3 after, p<0.001; females: 48.2+/-1.4 before vs 49.4+/-2.1 after,
      p<0.05). BFM was reduced by licorice: (male: before 12.0+/-2.1 vs after 10.8+/
      2.9%, p<0.02; female: before 24.9+/-5.1 vs after 22.1+/-5.4, p<0.02); plasma
      renin activity (PRA) and aldosterone were suppressed. Licorice was able to reduce
      body fat mass and to suppress aldosterone, without any change in BMI. Since the
      subjects were consuming the same amount of calories during the study, we suggest
      that licorice can reduce fat by inhibiting 11beta-hydroxysteroid dehydrogenase
      Type 1 at the level of fat cells.

PMID- 14594117
TI  - Is the effect of fine-needle aspiration biopsy on the thyroid nodule volume
      important to evaluate the effectiveness of suppression therapy?
AB  - Fine-needle aspiration biopsy (FNAB) is recommended for the initial evaluation of
      thyroid nodule. If a benign cytology is obtained, suppression therapy with
      levothyroxine is the first choice in the management of nodular goiter with a
      follow-up of nodule size with ultrasonography, but the effects of FNAB have not
      been taken into consideration in this approach. We aimed at evaluating the effect
      of FNAB on thyroid volume and other ultrasonographic dimensions by measurement of
      these parameters before and immediately after the procedure, and in later
      periods, and to clarify the necessity of regarding the effects of FNAB on
      thyroid. Forty-six patients (34 females, 12 males; mean age: 36.3+/-10.7 yr) with
      solitary thyroid nodules were included in the study. The nodules were solid in
      ultrasonography, thyroid function tests were normal and results of FNAB were
      found as benign cytology. Thyroid hormone suppression therapy was not initiated.
      Ultrasonographic measurements were made before FNAB, repeated immediately after
      FNAB, and 1 month and 6 months later. There were no statistically significant
      changes in the mean thyroid nodule volume, nodule area and circumference of
      patients before, immediately after FNAB, 1 month and 6 months later. Size
      differences and individual variability at each time period were analyzed. These
      parameters changed by more than 10% in a great majority (69.5-78.2%) of patients,
      and more than 50% change was observed in 17.3-26.0% of patients. Changes in
      thyroid dimensions were bi-directional, both increment and decrement being
      noticed. It was thought that this is the reason why there was no significant
      change in mean nodule volume, area and circumference. Evaluating the difference
      in nodule volume according to ultrasonographic parameters obtained before FNAB
      may be misleading because of the individual change in these parameters with FNAB.
      It may be useful to evaluate the nodule size and volume closely after FNAB to
      make a true correspondence of these parameters in the long term.

PMID- 14594118
TI  - Is hyperprolactinemia associated with insulin resistance in non-obese patients
      with polycystic ovary syndrome?
AB  - Insulin resistance is common in polycystic ovary syndrome (PCOS). Moderate
      elevations in serum PRL concentration may contribute to insulin resistance in
      PCOS. The aim of this study was to determine PRL on development of insulin
      resistance in non-obese hyperprolactinemic patients with PCOS. Ninety-eight non
      obese subjects with PCOS and 100 non-obese healthy control were accepted in the
      study. Serum glucose, lipids, androgens, free androgen index (FAI),
      gonadotropins, fat mass and percentage, SHBG, and insulin levels were measured.
      Homeostasis model assessment (HOMA) was used as index of pancreatic beta-cell
      function and tissue insulin sensitivity. Independent t-test was used in
      comparison of results. In patients with PCOS, FAI and mean HOMA-(%B) level were
      higher than in the control group (p<0.0001), whereas mean HOMA-(%S) in subjects
      with PCOS was lower than in the control group (p<0.0001). Patients with PCOS were
      divided into subgroups according to their serum prolactin level (< 24 or > or =
      24 ng/ml). Although FAI was not different, mean insulin and HOMA-(%B) levels in
      hyperprolactinemic patients were higher than in normoprolactinemic subjects
      (p<0.001). HOMA-(%S) in hyperprolactinemic patients with PCOS was lower than in
      normoprolactinemic patients (p<0.002). In conclusion, PCOS is associated with
      insulin resistance; non-obese hyperprolactinemic PCOS patients may be more
      insulin-resistant than normoprolactinemics and there may be an association
      between hyperprolactinemia and insulin resistance in PCOS.

PMID- 14594119
TI  - Oxyphilic and non-oxyphilic thyroid carcinoma cell lines differ in expressing
      apoptosis-related genes.
AB  - Oxyphilic tumors of the thyroid are characterized by mitochondrion-rich cells and
      extensive DNA fragmentation. In order to clarify if a different expression of
      apoptosis-related genes could be responsible for DNA fragmentation in oxyphilic
      cell tumors, two thyroid follicular carcinoma-derived cell lines, having
      oxyphilic (XTC.UC1) and non-oxyphilic (WRO) features, were compared applying a
      gene array technique. Under basal culture conditions, several pro-apoptotic genes
      [caspases 3 and 10, Fas and the tumor necrosis factor-related apoptosis-inducing
      ligand (trail) genes] were switched on in oxyphilic, but not in non-oxyphilic
      cells. No difference in the mitochondrial apoptosis-related genes (bax, bad, bcl
      family etc.) was observed. Using the ISEL technique, the extent of DNA
      fragmentation did not differ under basal conditions in the two cell lines.
      Conversely, following an oxidative pro-apoptotic stress (6-h methylene blue
      treatment and light exposure), XTC.UC1 cells showed an extensive DNA
      fragmentation (up to 70% of cells), dramatically exceeding that observed in WRO
      cells (up to 20% of cells). In contrast, the oxidative stimulus induced a
      remarkable apoptosis gene activation in non-oxyphilic WRO cells only. These
      results suggest that oxyphilic cells may have a unique silent activation of a pro
      apoptotic phenotype, which could be responsible for DNA instability and lead to
      cell death as the consequence of an increased sensitivity to ischemic stresses,
      as frequently observed in vivo.

PMID- 14594121
TI  - Brown jaw tumors: today's unusual presentation of primary hyperparathyroidism.
AB  - Primary hyperparathyroidism (pHPT) has changed its clinical features in the last
      decade becoming a mild biochemical disease, in which the classical fibrous cystic
      osteitis is a rare complication. The more frequent bone involvement in primary
      hyperparathyroidism is observed at the distal 1/3 of the radius, where the
      cortical bone is primarily represented. However, lumbar and femoral osteopenia or
      osteoporosis prevalently affect hyperparathyroid post-menopausal women. We report
      two, otherwise healthy, young male patients, who presented a painful jaw
      swelling. In both patients standard radiographic imaging revealed a low-density
      well-defined lesion, which caused jaw bone destruction. High levels of serum
      calcium (14.1-16.6 mg/dl, n.v. 8.1-10.4) and PTH (1172-1928 pg/ml, n.v. 10-65)
      indicated the presence of pHPT associated with hypertension, asymptomatic renal
      involvement and osteoporosis with normal serum 25-hydroxyvitamin D levels in both
      patients. A single huge parathyroid adenoma was successfully removed and within 2
      months jaw lesions were almost completely re-mineralized without any other
      therapeutic intervention in both patients. In conclusion, although brown jaw
      tumors are a rare complication of the hyperparathyroidism, they should be
      considered and identified in young patients with severe pHPT. Moreover, such a
      complication seems to be independent from vitamin D deficiency, suggesting the
      involvement of other pathogenetic factors.

PMID- 14594120
TI  - Circulating endogenous digitalis-like factor(s) (EDLF) in man is derived from the
      adrenals and its secretion is ACTH-dependent.
AB  - Adrenal origin and ACTH-dependent secretion of endogenous digitalis-like
      factor(s) (EDLF) was investigated. Twelve normal weight normotensive subjects
      (normal group) and 10 patients with Addison's disease (Addison group) were
      subjected to prolonged ACTH stimulation with 1 mg tetracosactin-depot im. Blood
      sampling was at 0 and 240 min. Digitalis-like reactivity was monitored in plasma
      extracts (combined organic solvent solid phase method) by digoxin and ouabain
      radioimmunoassay (RIAD and RIAO, respectively). 3H-ouabain concentration on
      erythrocytes (OBS) was also determined. Na+, K+-ATPase inhibition by normal
      plasma extract was tested by measuring Vmax and Km of 86Rb+-transport into human
      erythrocytes. In the normal group basal median plasma concentrations RIAD (0.07
      nmol/l) and RIAO (0.89 nmol/l) increased significantly after ACTH administration
      (median 0.31 and 1.83, respectively; Wilcoxon, p<0.01). In contrast, in the
      Addison group no plasma RIAD and RIAO reactivity was detected before or after
      ACTH administration with minor exceptions. The OBS remained unchanged in the
      Addison group at 0 and 240 min; in the normal group there was a significant
      decline at 240 min (Wilcoxon, p<0.05) implying increase in circulating EDLF after
      ACTH stimulation. In the 86Rb+-transport experiments, 2 nmol/l ouabain or 2
      nmol/l plasma-extracted ouabain reactivity both significantly impaired substrate
      affinity equally increasing Km without affecting Vmax. In men, the adrenals may
      produce and secrete EDLF, whose secretion appears to be ACTH-dependent.

PMID- 14594122
TI  - Coexistence of a parathyroid adenoma and parathyroid cyst causing primary
      hyperparathyroidism.
AB  - The association of a functional parathyroid cyst with a parathyroid adenoma is an
      uncommon finding. In this report we describe the clinical history of a 60-yr-old
      man, presenting with the following findings: hypercalcemia (18.9 mg/dl), elevated
      serum parathormone levels (1320 pg/dl), hypercalciuria (228 mg/dl), and
      hyperphosphaturia (155 mg/dl). Neck ultrasound, magnetic resonance imaging (MRI)
      and 99Tc Sestamibi scintigraphy led to the identification of a left parathyroid
      adenoma, located at the lower pole of the left thyroid gland lobe, associated
      with a parathyroid cyst, located at the upper extremity of the same thyroid lobe.
      Parathyroidectomy was performed and the histological examination confirmed the
      diagnosis of a parathyroid adenoma with aspects of cystic degeneration and an
      upper parathyroid cyst. Analysis of the crystal clear intracystic fluid showed
      elevated parathyroid hormone (PTH) levels (137.000 pg/ml). The patient is
      normocalcemic at 2 yr after surgery without signs of recurrent parathyroid
      enlargements. Aetiology, diagnosis and management of parathyroid cyst will be
      discussed.

PMID- 14594123
TI  - Diabetic mastopathy: a case report.
AB  - Diabetic mastopathy, although reported since 1984, is a poorly recognized
      diabetes complication. It more frequently affects pre-menopausal women with Type
      1 diabetes mellitus and microvascular complications. The pathogenesis of this
      condition is believed to involve mammary tissue autoimmune reaction to the
      accumulation of abnormal matrix proteins, caused by hyperglycemia. The lesion
      often simulates breast cancer; its recognition, therefore, is important to avoid
      unnecessary diagnostic procedures and surgical treatments. We now report a case
      of diabetic mastopathy which clinically simulated breast cancer in a young pre
      menopausal diabetic woman who, after sonography and mammography, was suggested
      surgery under suspicion of breast cancer. Histopathological examination by core
      biopsy ruled out malignancy.

PMID- 14594124
TI  - Thyroid ultrasound as a predicator of thyroid disease.

PMID- 14594125
TI  - Skeletal muscle insulin resistance: is it important for the pathogenesis of type
      2 diabetes after all?

PMID- 14594126
TI  - Andropause: to treat or not to treat?

PMID- 14594128
TI  - Primary biliary cirrhosis: historical perspective.
AB  - PBC is an old disease first described in 1851. It's predilection for women and
      its association with other autoimmune diseases suggests an immune based
      pathogenesis, but epidemiologic studies indicate that genetic and environmental
      factors play a role in the pathogenesis of PBC. The serologic hallmark for PBC,
      namely the antimitochondrial antibody, was first identified in 1965 and remains
      the most sensitive and specific hallmark for this disease. When first described,
      primary biliary cirrhosis was universally fatal but asymptomatic cases now
      represent more than 60% of cases diagnosed, less than half of whom will die of
      their liver disease. No specific therapy that effectively stops or reverses
      disease progression has been identified, thus it behoves investigators to
      aggressively pursue identification of the etiology of PBC.

PMID- 14594127
TI  - Diagnosis and management of Addison's disease during pregnancy.
AB  - Although primary adrenal failure is considered a rare condition, recent
      epidemiological studies indicate a rising incidence of the disease owing to the
      increase of autoimmune disorders. Addison's disease may be a life-threatening
      condition and the occurrence of pregnancy has been considered as a dangerous
      event. Nowadays, adrenal insufficiency during pregnancy is associated with high
      incidence of serious fetal and maternal complications, as fetal death in utero
      and post-partum adrenal crises, only if the disorder is not recognized and
      adequately treated. In this article pathophysiological aspects, clinical features
      and guidelines of management of pregnancy in Addison's disease are reviewed.

PMID- 14594129
TI  - Primary biliary cirrhosis--presentation and diagnosis.
AB  - Primary biliary cirrhosis is predominantly seen in middle-aged women. Typical
      symptoms are fatigue, pruritus, and abdominal pain. Jaundice develops in the
      endstage disease. At presentation, about 40% of the patients are asymptomatic,
      but 30% to 50% already have hepatomegaly, and 15% present with splenomegaly. Even
      patients with fully developed liver cirrhosis may be free of symptoms. Abnormal
      physical signs and advanced histological stage are more frequent in symptomatic
      than in asymptomatic patients. Fatigue, pruritus, and Sjogren's syndrome are more
      common in women than men, but other signs and symptoms do not differ in the two
      sexes. PBC is associated with a large variety of other diseases, like
      arthropathy, CREST syndrome, autoimmune thyroiditis, and so on, which in addition
      will or will not produce symptoms. Hepatocellular carcinoma is a rare
      complication in women, but more frequent in men. Diagnosis can be established by
      the triad antimitochondrial antibodies (AMA), cholestatic indices, and liver
      histology, diagnostic or compatible with PBC. When AMA are not detected, then
      antinuclear antibodies (autoantibodies against gp.210 and others) can be detected
      in 50% of AMA-negative patients. AMA titers do not correlate with the course of
      the disease nor histological progression. After liver transplantation, AMA recur
      in nearly 100%. The liver enzyme pattern in PBC patients is cholestatic: alkaline
      phosphatase and gammaglutamyltransferase increase to 10 or more times the upper
      limit of normal. The amount of enzymes does not correlate with disease
      progression or stage of the disease. The only prognostic factor in PBC is serum
      bilirubin. AMA-negative patients account for about 10% to 15%. Routine
      biochemical tests are not different from AMA-positive patients, but usually
      higher ANA, SMA, and IgG concentrations are detected. Histologically, it is PBC.
      The overlap-syndrome, autoimmune hepatitis-PBC presents with the histological
      features of autoimmune hepatitis and PBC, with AMA, ANA, or SMA. Imaging
      procedures are not helpful for the diagnosis of PBC, except for liver histology.
      Histologically, four different stages can be assessed, ranging from florid bile
      duct lesions, ductular proliferation, and fibrosis to liver cirrhosis. Liver
      histology is of interest for the assessment of the diagnosis and for staging of
      the disease.

PMID- 14594130
TI  - Antimitochondrial and other autoantibodies.
AB  - Primary biliary cirrhosis (PBC) is characterized by the presence of high-titer
      disease specific autoantibodies directed against mitochondrial antigens (AMA) of
      the inner mitochondrial membrane, that are members of the 2-oxo acid complex.
      Among numerous other autoantibodies found in PBC the focus of ongoing studies is
      on the PBC-specific anti-nuclear antibodies, that are of diagnostic and clinical
      relevance since they can be used as a 'positive tool' in the diagnosis of AMA
      negative PBC while at the same time identifying a subgroup of patients with more
      advanced liver disease.

PMID- 14594132
TI  - The epidemiology of primary biliary cirrhosis.
AB  - Over the last 30 years, many studies have reported on the epidemiology of PBC.
      Substantial increases in prevalence were noted in the majority of studies
      examining longitudinal data, and several have reported increases in the incidence
      of PBC. Furthermore, although it is difficult to compare studies directly, as
      methods of case ascertainment have greatly improved over this period, there has
      been a definite trend toward increasing prevalence (and also possibly incidence)
      across studies. Together, these data strongly suggest that in many countries, the
      frequency with which PBC is diagnosed has increased considerably between 1980 and
      the present time. The reasons for this change may be complex. There may have been
      a true increase in the incidence of PBC, reflecting either increased exposure to
      a currently unknown environmental etiological agent or demographic changes with
      an increased elderly, at-risk population. The prevalence may have further
      increased due to increased survival of patients, either due to improved care or
      earlier diagnosis. Some of the apparent increase in PBC frequency may also be
      artifactual, however, resulting from increased use of diagnostic tests,
      particularly autoantibody screens. This may be due to increased availability of
      testing, increased clinician (or patient) awareness of PBC, increased use of
      testing in well-person screening, or increased investigation of ill-defined
      symptoms. Furthermore, there may also have been an improvement in clinicians'
      ability to recognize PBC on the basis of the clinical picture (in one study, 37%
      of patients whose clinical results indicated a diagnosis of PBC were not
      recognized by the clinician caring for the patient at that time). The last factor
      alone suggests that all studies based only upon cases known to interested
      clinicians have probably substantially underestimated the prevalence of disease.
      Whatever the reason, the recognized epidemiology of PBC has dramatically changed
      over the past 30 years. It is now a frequent cause of liver morbidity, and
      patients with PBC are significant users of health resources, including liver
      transplantation. Large geographical variations in disease frequency, both between
      and within studies, tantalizingly suggest the presence of as-yet-unidentified
      risk factors. This should be further followed up with new analytical
      epidemiological studies. Only two case control studies have examined risk factors
      for PBC, and these have been either relatively small or used poorly defined and
      potentially biased experimental groups. These need repeating in new settings. We
      suggest that, as with other diseases, modern epidemiological instruments used in
      well-designed studies may provide important clues to the cause or causes of this
      disease.

PMID- 14594131
TI  - Natural history of primary biliary cirrhosis.
AB  - The natural history of PBC is characterized by slowly progressive cholestasis
      with liver damage, development of cirrhosis and its complications, and death,
      unless the patient undergoes liver transplantation. The disease has at least
      three clinical presentations, each with a different course and prognosis: the
      silent and usually less aggressive form, the asymptomatic form, and the
      symptomatic form. There are no identifiable features that distinguish the
      asymptomatic population who will remain symptom-free from those patients who will
      develop symptoms. As expected, the survival is longer in asymptomatic than in
      symptomatic patients. Overall survival of asymptomatic PBC is shorter than for an
      age- and gender-matched control population, but the patients remaining
      asymptomatic had a survival equal to that of the general population. Natural
      history studies have identified several variables associated with survival,
      particularly age, bilirubin, albumin, prothrombin time, ascites, encephalopathy,
      and advanced histological stage. Development of esophageal varices and
      hepatocellular carcinoma can also affect survival. Serum bilirubin level is,
      however, the most heavily weighted prognostic variable and can be used as a
      simplistic prognostic index for patients with PBC. In the last two decades,
      natural history models have been developed that include clinical, biochemical,
      and histological variables, the most popular being the Mayo model. It has the
      advantage ofavoiding histological variables, and therefore can be applicable to a
      broad spectrum of patients with PBC. The models may also be used to evaluate the
      efficacy of different new treatments. Prognostic models based on serial
      measurements of the independent predictors of poor prognosis would lead to a more
      accurate prediction of survival; however, they probably will not replace clinical
      outlook.

PMID- 14594133
TI  - Genetic factors in the pathogenesis of primary biliary cirrhosis.
AB  - Current knowledge of the genetic basis of PBC is at best incomplete and at worst
      poor. Studies so far may be used as a guide to the pitfalls that await unwary
      investigators and also in deciding where to look and which genes or systems are
      most likely to yield informative results. The Human Genome Project has revealed a
      vast array of polymorphism that is too much to contemplate even with the best of
      current techniques. The crucial processes are the selection of candidates and
      study design. The strong genetic associations so far in PBC are with chromosomes
      6p21.3 and 2q and include; HLA DRBI*08 haplotypes, CTLA4* G and IL1RN-IL1B
      haplotypes, CASP8, and nramp1. Many of the latter should be considered with
      caution until confirmed in independent series. Other associations with MBL, APOE
      and VDR remain to be confirmed. There are also several informative negatives,
      MMP3 and IL10 for example. It is unlikely that the only genes that influence
      disease susceptibility and progression in PBC are immunoregulatory genes
      concerned with T cell immunity. Recent studies indicate a new era for
      immunogenetics, when genes encoding all immune active proteins may be considered
      as candidates. One should not concentrate solely on the immune response as recent
      investigations of mannose binding lectin and apolipoprotein-E testify. One is
      only just beginning to understand the genetic basis of complex diseases like PBC.
      The key issues for future investigators are: defining the mechanisms where by
      self tolerance is broken, defining the mechanisms that determine the rate of
      disease progression, and identifying genetic markers to predict progression and
      malignancy. Assessing the genetic basis of variability in disease progression.
      The significant variation in rate of progression of PBC has led to the hypothesis
      that genes, in addition to contributing to disease susceptibility, may also
      determine the rate of disease progression. Several of the studies mentioned
      earlier have suggested associations between alleles at polymorphic loci and rate
      of progression . All studies performed to date, however, have been retrospective
      in nature. One problem inherent in such studies is that of definition of disease
      progression. One simple definition, that of histological progression to Scheuer
      stage IV disease , requires liver biopsy. The need to perform repeat biopsies
      raises ethical problems in cases where there is no other clinical indication.
      Studies of histologic progression in patients in the control arm of therapeutic
      trials represent one scenario where repeat biopsy would be indicated. However,
      the typical time course of such trials is 2 years, insufficient for meaningful
      assessment of disease progression and natural history, particularly in PBC where
      there is marked heterogeneity and, as a result, tissue sampling error. Yet,
      alternative systems for assessing disease progression, such as the Mayo
      prognostic score, lack sensitivity in any scenario other than existing advanced
      disease. Outlook for the future. Clinical observations support a significant
      genetic component to disease susceptibility. Elucidating predisposing genetic
      associations will markedly assist in understanding the pathophysiology of
      disease. Investigations to date have been restricted to various community-based
      case-control association studies, with well-recognized limitations. In future SNP
      maps and haplotype maps from the Human Genome Project will be available. Studies
      will require the collection of several well-characterized patients. To meet the
      required statistical power this will necessitate collaboration on a national and
      international scale. It is essential that these studies address the relationship
      between genes and disease progression. The possibility of identifying, in the
      early stages of disease, patients who are at elevated risk for more rapid
      progression, would have obvious clinical benefit in terms of patient management
      and therapy.

PMID- 14594134
TI  - Autoimmune overlapping syndromes.
AB  - The overlap syndrome raises several questions. First could these patients have
      two coincident autoimmune diseases? Such possibility cannot be discarded in
      particular in the setting of consecutive occurrence of the two conditions (eg,
      PBC followed by AIH) and this is consistent with the fact that autoimmune
      diseases are associated with one another in about 5% to 10% of cases.
      Furthermore, it is presumed that they share similar genetic susceptibility. A
      second possibility could be that overlap syndrome represents the middle of a
      continuous spectrum of two autoimmune liver diseases. The systematic study of the
      relationships between elementary histologic lesions and biochemistries in "pure"
      PBC patients pleads strongly for such a hypothesis. Pure PBC is characterized by
      2 different groups of elementary lesions that are not interrelated: first, florid
      bile duct lesions and bile duct paucity and second, lymphocytic piecemeal
      necrosis and lobular necro-inflammatory changes. Furthermore, the first set of
      lesions is selectively associated with biochemical cholestasis and IgM levels,
      whereas the second set of lesions is selectively associated with serum
      transaminase activities and IgG levels. These observations are consistent with
      the assumption that two main mechanisms are involved in the progression of liver
      injury in PBC. The first is bile duct destruction leading to chronic cholestasis
      and fibrosis of biliary pattern. The second is lymphocytic piecemeal necrosis of
      hepatocytes, which tends to lead to cirrhosis, the pattern of which resembles
      cirrhosis following various forms of chronic active hepatitis. The author has
      therefore speculated that the picture of pure PBC results always forms the
      clinical and biochemical expression of the two main histologic lesions, and
      combination of these processes might explain why the spectrum of PBC varies from
      typical PBC to AIH or PBC overlap. A third hypothesis is that an exaggerated
      hepatitic response in PBC is associated with the HLA haplotype commonly seen in
      AIH, eg, B8, DR3, DR4. Further studies are obviously needed to confirm such an
      attractive hypothesis. Other possible explanation for the concurrent occurrence
      of features of both conditions in the same individual includes the selective
      modulation of HLA class 1, class 2 expression and Rantes by cholestasis itself
      and in particular bile acids. It is conceivable that the degree of interface and
      lobular inflammation in PBC and PSC may be modulated by chemokines, their
      receptors, and the parenchymal concentrations of individual bile acids that are
      all, at least in part, genetically determined.

PMID- 14594135
TI  - Pruritus and fatigue in primary biliary cirrhosis.
AB  - Pruritus and fatigue are the most common symptoms of patients with PBC, and both
      have marked negative impact on quality of life. Over the past decade, evidence
      has emerged supporting a role of the central nervous system in the pathogenesis
      of these two common manifestations of PBC. There is no evidence that the pruritus
      of cholestasis is mediated in the skin. Clinical and laboratory data do support a
      role of the opioid neurotransmitter system in the mediation of the pruritus of
      cholestasis; a central mechanism has been proposed. Treatment with opiate
      antagonist is thus a specific alternative. Studies of the behavioral consequence
      of the pruritus of cholestasis, scratching activity, allow for the design of
      clinical trials with objective end-points. The etiology of fatigue is unknown. A
      central component is being considered. The identification of objective
      alterations in fatigue and the adoption of a definition that incorporates the
      perception and the behavioral consequences of fatigue should facilitate the
      development of objective methodology. The potential role of various
      neurotransmitter systems, including the serotonin system and the opioid system,
      in the mediation of the fatigue of PBC seems to merit further investigation.

PMID- 14594136
TI  - Management of osteoporosis, fat-soluble vitamin deficiencies, and hyperlipidemia
      in primary biliary cirrhosis.
AB  - Osteoporosis is several times more common in patients with PBC compared with the
      general population. Maintaining adequate intake of calcium and vitamin D is
      important for prevention of bone loss. The use of bisphosphonates or vitamin K to
      improve bone mineral density in osteopenic patients seems promising and needs to
      be further evaluated. Patients with PBC may develop fat-soluble vitamin
      deficiencies, especially vitamins A and D; serum levels should be investigated in
      patients considered at risk with the aim of recommending appropriate replacement
      therapy. Finally, hyperlipidemia in PBC does not seem to be associated with an
      increased risk of atherogenesis. New therapies in this patient population are
      currently under investigation.

PMID- 14594137
TI  - Preventative therapy in primary biliary cirrhosis.
AB  - Because the etiology of PBC is still unknown, therapies remain empirical.
      Moreover, no contributions on preventative therapy supported by evidence-based
      medicine have been published to date. However, there are at least two groups of
      subjects who might benefit from preventative therapy: (1) subjects with normal
      liver enzymes who are found AMA-positive during autoantibody screening and (2)
      subjects transplanted for PBC with no histologic or biochemical signs of disease
      recurrence. The key questions are whether any therapy should be proposed to these
      subjects, since the natural history of the disease is very long, and what kind of
      treatment should be prescribed. UDCA is a well-tolerated, definitely
      "physiologic" treatment, but it is expensive and two recent meta-analyses
      question its benefit on survival. Current theory considers PBC an autoimmune
      disease, with a genetic predisposition, possibly triggered by an infectious agent
      or xenobiotic. If this is so, gene therapies might be the most promising future
      preventative therapies. For the time being, however, the only practical
      preventative management is in regards to the complications of PBC, namely
      osteopenia and portal hypertension.

PMID- 14594138
TI  - Primary biliary cirrhosis: specific treatment.
AB  - No single agent or combination of agents has been shown to unequivocally delay
      the need for liver transplantation or reduce mortality in patients with PBC.
      Given this uncertainty, what, if any, specific therapy should be recommended? The
      agents with the strongest scientific proof of efficacy in well-designed clinical
      trials are ursodiol, azathioprine, and cyclosporine. Ursodiol is clearly the
      least toxic of these three. Other agents, such as methotrexate, have shown
      impressive results in anecdotal studies but have never been adequately tested in
      randomized clinical trials. Thus, based on the current evidence, imperfect as it
      is, ursodiol appears to be the safest and potentiaily the most effective specific
      therapy for patients with PBC. Azathioprine and methotrexate may be the best
      alternatives for patients who cannot tolerate or do not respond to ursodiol
      therapy, primarily because their safety has been established in large and lengthy
      clinical trials. Cylosporine could be considered in patients who fail other
      treatments (Table 3). We can hope that a safe, highly-effective treatment for
      patients with PBC will ultimately be discovered. Trials to unequivocally
      demonstrate the efficacy of new agents will have to be extremely well designed,
      however, and will require large numbers of patients followed for an extended
      period of time.

PMID- 14594139
TI  - Liver transplantation for primary biliary cirrhosis.
AB  - Liver transplantation is the accepted treatment for patients with end-stage liver
      disease or intractable symptoms secondary to primary biliary cirrhosis (PBC), and
      has proven survival benefit. Indications for transplantation are an unacceptable
      quality of life or anticipated death in less than 1 year. Although there are a
      number of prognostic models, serum bilirubin provides the simplest guide to
      transplantation timing. Those grafted for PBC are at greater risk of developing
      chronic rejection, and are less likely to be successfully weaned from
      immunosuppression than those grafted for other indications. Following
      transplantation, antimitochondrial antibodies persist and histological features
      of recurrent PBC may be seen in the allograft in up to 50% by 10 years; however,
      at least in the medium-term, this rarely causes clinical problems.

PMID- 14594140
TI  - Primary biliary cirrhosis: the future.
AB  - The answers to these questions are key to understanding the pathogenesis of PBC.
      Although the study of PBC is significantly retarded by the lack of an adequate
      animal model, the molecular technology to address these issues is advancing
      rapidly. In addition, the ability to isolate and culture human biliary epithelial
      cells greatly facilitates in vitro studies. With the advent of these tools,
      investigators are well poised to address the important issues of PBC in the
      future.

PMID- 14594141
TI  - CT urogram.

PMID- 14594142
TI  - Case of the month. Acute cholecystitis.

PMID- 14594143
TI  - Imaging of sinonasal anatomy and inflammatory disorders.
AB  - The widespread acceptance of functional endoscopic sinus surgery (FESS)
      underscores the importance of understanding the relevant anatomy of the paranasal
      sinuses as a means of providing a roadmap to the otorhinolaryngologist prior to
      surgery. The radiologist can address important imaging issues for the ear, nose,
      and throat (ENT) surgeon before FESS is undertaken. There are two main questions
      that the radiologist should address: 1. Are there anatomic features on the
      computed tomography (CT) scan that predispose the patient to impaired mucociliary
      clearance? 2. Are there anatomic features that pose a surgical hazard?

PMID- 14594144
TI  - Staging renal cell carcinoma with helical CT: the revised 1997 AJCC and UICC TNM
      criteria.
AB  - The TNM staging system for renal cell carcinoma, revised in 1997 by the UICC and
      AJCC, has important implications for tumor prognosis and surgical planning.
      Multislice helical CT of the kidneys plays a vital role in the detection,
      characterization, and staging of renal cell carcinoma, and for surgical planning.
      Radiologists should be familiar with state-of-the-art helical CT techniques, the
      revised TNM staging criteria, and the varied appearances of renal tumors, tumor
      cell types, and the wide variety of metastatic disease that occurs in advanced
      cases.

PMID- 14594145
TI  - [Therapeutic hemapheresis].
AB  - BACKGROUND: This is the first survey of therapeutic hemapheresis in Norway. The
      purpose was to collect data from all Norwegian dialysis and blood units
      performing hemapheresis treatment and stem cell collection for comparison with
      Swedish data. MATERIALS AND METHODS: Questionnaires were sent to all regional and
      central hospitals in Norway including two specialized centres for stem cell
      apheresis. The questions included the number of hemapheresis procedures,
      patients, and indications. RESULTS: All units responded to the questionnaire.
      There were 17 dialysis units; seven blood units and two special units who
      performed 2,141 procedures. 12 units did not carry out any hemapheresis treatment
      at all. There were five stem cell collections per 100,000 inhabitants and 42.5
      therapeutic apheresis procedures per 100,000 inhabitants. INTERPRETATION:
      Hemapheresis treatment is performed in all Norwegian health regions. The
      indications are quite similar to those reported from Sweden except for stem cell
      collections and erythrocytaphereses. The dominance of the dialysis units in the
      total number of procedures performed and the prominent use of filtration
      techniques are special features of the Norwegian practice of apheresis.

PMID- 14594146
TI  - The Palliative Care Research Society in the UK.

PMID- 14594147
TI  - Respite in palliative care: a review and discussion of the literature.
AB  - Family caregivers, who are patients' relatives and friends (hereafter called
      carers), play a significant and arguably most important role in enabling patients
      to make choices about their place of care during advanced disease and in the
      terminal phase. Relatively little attention has been directed towards identifying
      the needs of carers who find themselves in this position and what interventions
      (if any) might best support them in continuing to provide care to the patient
      during the illness and dying trajectory. What evidence there is suggests that
      while some aspects of caring are looked on positively, carers also experience
      challenges in maintaining their physical and psychological health and their
      social and financial wellbeing. One common recommendation is that respite
      facilities be provided. The purpose of this paper is to consider the definitions
      and assumptions that underpin the term 'respite' and its impact on the physical,
      psychological and social outcomes of carers in palliative care contexts. We
      conducted a review of the literature, which involved searching five electronic
      databases: Web of Science, Medline, CINHAHL, Cochrane Database System Review and
      Social Sciences Citation Index. The search identified 260 papers, of which 28
      related directly to adult respite care in specialist palliative care. These
      papers were largely concerned with descriptive accounts of respite programmes,
      guidance on referral criteria to respite services or were evaluating the effects
      of respite on the patient rather than the impact on the carer. We did not
      identify any empirical studies assessing the effects of respite provided by
      specialist palliative care services on carer outcomes. There is insufficient
      evidence to draw conclusions about the efficacy of offering respite care to
      support carers of patients with advanced disease. We, therefore, draw on the
      wider literature on carers of adults with chronic disease to consider the impact
      of respite services and offer suggestions for further research.

PMID- 14594148
TI  - Low-dose methadone has an analgesic effect in neuropathic pain: a double-blind
      randomized controlled crossover trial.
AB  - The analgesic effectiveness and adverse effect incidence of a daily dose of 10 or
      20 mg of oral methadone were evaluated in 18 patients with a diverse range of
      chronic neuropathic pain syndromes, who had all responded poorly to traditional
      analgesic regimens. Analgesia was seen after each dose of methadone. As compared
      with placebo, the 20 mg daily dose (given as 10 mg bd) resulted in statistically
      significant (P = 0.013-0.020) improvements in patient Visual Analogue Scale
      ratings of maximum pain intensity, average pain intensity and pain relief,
      recorded at the same time daily. The analgesic effects extended over 48 hours, as
      shown by statistically significant (P = 0.013-0.020) improvements in all three
      outcomes on the rest days instituted between each daily dose. Analgesic effects
      (lowered maximum pain intensity and increased pain relief, on the day of dosing
      only) were also seen when the lower daily dose of 10 mg methadone (given as 5 mg
      bd) was used, but these failed to reach statistical significance (P = 0.064 and
      0.065, respectively). Interpatient analysis showed that the analgesic effects
      were not restricted to any particular type of neuropathic pain. Patient
      compliance was high throughout the trial. One patient withdrew during the 10 mg
      and six during the 20 mg methadone treatment periods. This is the first double
      blind randomized controlled trial to demonstrate that methadone has an analgesic
      effect in neuropathic pain.

PMID- 14594149
TI  - Symptoms and concerns amongst cancer outpatients: identifying the need for
      specialist palliative care.
AB  - This study aimed to define and prioritize the need for specialist palliative care
      (SPC) in cancer outpatient clinics. A validated assessment tool, the Symptoms and
      Concerns Checklist, was used to determine the prevalence and severity of symptoms
      and concerns. The checklist was completed by 480 outpatients with a cancer
      diagnosis. Sixty patients from each of eight primary tumour groups (lung, breast,
      gastrointestinal, gynaecological, urological, head and neck, brain and lymphoma)
      were recruited. The majority of patients (over 90%) rated 27 of the 29 checklist
      items, reporting a mean of 10 items as current problems. The influences of
      disease site and status, demographic factors and treatment on the number and type
      of symptoms and concerns reported were investigated. The highest number of
      symptoms and concerns and most severe problems were reported by patients with
      lung cancer, followed by those with brain tumours; the lowest by those with
      lymphoma and urological tumours. A high proportion of patients (83%) reported one
      or more items likely to benefit from SPC intervention. The results of this study
      suggest an extensive need for better symptom control in all cancer outpatients
      and in centres where SPC resources are limited, priority could be given to
      patients attending lung and brain tumour clinics.

PMID- 14594150
TI  - Depressive symptoms in advanced cancer. Part 1. Assessing depression: the Mood
      Evaluation Questionnaire.
AB  - OBJECTIVE: A prospective cohort study evaluated the performance and acceptability
      of the cognitive based Mood Evaluation Questionnaire (MEQ) in assessing
      depressive symptoms over time in patients with advanced cancer. The structured
      clinical interview for DSM-III-R (SCID) and the single-item interview screening
      question were also administered. METHOD: Forty-five advanced cancer patients were
      followed monthly for up to six interviews (108 interviews in total). RESULTS: The
      MEQ and SCID had moderate agreement (weighted kappa 0.52 over all interviews). At
      first interview, 26 (58%) patients were depressed using MEQ, seven (16%) of these
      severely. Attrition rates were high for subsequent interviews. The assessment
      process was considered positive by 92% patients, and acceptable as a single and
      repeat measure. Positive responses to MEQ questions about worthlessness, death
      and self-harm were strong predictors of current depressed mood. CONCLUSION: The
      MEQ has potential as a useful alternative to SCID in assessing depressive
      symptoms in a palliative care population, and can be used by nonpsychiatric
      trained professionals. It is positively received by patients and acceptable as a
      repeat measure. Most patients appreciate being asked about their mood in depth,
      including questions around death and self harm.

PMID- 14594151
TI  - Depressive symptoms in advanced cancer. Part 2. Depression over time; the role of
      the palliative care professional.
AB  - OBJECTIVE: To survey changes in depressive symptoms over time in patients with
      advanced cancer using the Mood Evaluation Questionnaire (MEQ), and explore how
      effective Palliative Care Professionals (PCPs) are at assessing this. METHOD:
      Forty-five advanced cancer patients were followed monthly for up to six
      interviews (108 interviews in total). Selected clinical variables were recorded.
      RESULTS: At first interview, 26 (58%) patients were depressed using MEQ, seven
      (16%) severely. Attrition rates were high, with 28, 13, nine, seven and six
      patients available for subsequent interviews. A > 12-point increase in MEQ over
      sequential interviews was associated with reduced survival (Hazard ratio 3.2, CI
      1.2-8.4). PCPs recognized depressed mood, but underdiagnosed severe depression in
      9% of patients (CI 3-16%, P = 0.002). A past history of depression was a strong
      indicator of current depressed mood on the MEQ. CONCLUSION: Change in depressive
      symptoms over time is related to mortality in this patient cohort, patients with
      marked deterioration in mood dying earlier. PCPs usually recognize patients'
      depression but underestimate the severity of depressed mood.

PMID- 14594152
TI  - Perspectives on symptom control in patients receiving community palliative care.
AB  - To remain at home, terminally ill cancer patients need good symptom control and
      support from informal carers. Few studies have explored the influence of informal
      carers on symptom control and vice versa. This qualitative case study was carried
      out in a specialist palliative care service (SPCS) to explore the reasons why
      patients were admitted for inpatient care. Ten patients were systematically
      selected and the main carer and health professionals involved in their care were
      invited to participate. Semi-structured, audiotape recorded interviews were
      conducted and a thematic analysis performed on the transcripts, using the
      'Framework' approach. The results highlight the vital role that carers play in
      the assessment and management of symptoms in the community. However, carers
      reported difficulties in knowing what to monitor, how to interpret symptoms
      accurately and when to inform a professional. It was also reported that
      medication was not taken as it was prescribed and a number of reasons were given.

PMID- 14594153
TI  - General practice vocational training in the UK: what teaching is given in
      palliative care?
AB  - BACKGROUND: Palliative care is an integral part of the general practitioner's
      role and palliative care teaching and training should be available for GP
      registrars during vocational training. AIM: This study was carried out to
      evaluate the content, amount and nature of generic palliative care teaching
      during vocational training in the UK. METHOD: A postal questionnaire survey of
      all course organizers enquired as to whether palliative care teaching was
      included in the core training sessions; professional background of the teachers;
      teaching methods used; whether the local hospice was used as a resource and
      whether GP registrars were able to choose a post in a hospice within their
      training scheme. RESULTS: Three hundred and seventy-seven questionnaires were
      distributed and 240 were returned completed--a 64% response rate. A total of nine
      one-year schemes replied that they did not include any teaching in palliative
      care--the median amount of teaching given for one-year schemes was 4.75 hours and
      nine hours for the three-year schemes. Statistically significant differences were
      found in teaching on psychosocial issues and bereavement between one- and three
      year schemes. Less than half of all schemes included teaching on financial issues
      related to palliative care. Several schemes cited difficulties in accessing
      hospice placements and in accessing hospice medical staff to provide teaching.
      CONCLUSION: There is wide disparity in both the amount and content of teaching
      about palliative care within UK vocational training schemes. Difficulty in
      accessing placements within hospices and in accessing staff from such units to
      undertake teaching may be a barrier to effective and comprehensive palliative
      care teaching for doctors working in primary care. We suggest that a national
      generic curriculum of palliative care within primary care be implemented.

PMID- 14594154
TI  - Building bridges in palliative care: evaluating a GP Facilitator programme.
AB  - The objective of this study was to evaluate the impact of the Macmillan GP
      Facilitator Programme in Palliative Care on the knowledge, attitudes and
      confidence in symptom control of general practitioners (GPs), communication with
      patients and out-of-hours practice. GP Facilitators work on average for two
      sessions a week with practices in their locality. The design included a before
      and after study, with geographical controls matched on type of area (inner city,
      urban and rural) and broadly on Jarman scores using postal questionnaires sent to
      GPs. Scores measured change in GP awareness, attitudes and practice over two
      years of the intervention, derived from Likert scale responses to the postal
      questionnaires. Although overall few significant results were found, we did
      identify an increase in the use of palliative care guidelines in Facilitator
      districts, together with an increase in awareness of day care. The programme was
      associated with increased positive attitudes towards specialist palliative care
      services and results suggested increased satisfaction with out-of-hours services
      for patients. No change was found for confidence in symptom control and
      communication over diagnosis with cancer patients was less than in control
      districts. The design also incorporated a qualitative component, and from this we
      found the Facilitator programme to be popular with local GPs who valued the
      support of a colleague who knew the demands and constraints of general practice.
      In conclusion, we have demonstrated an impact of the GP Facilitator programme on
      GP awareness of, use and increased positive attitudes towards specialist
      palliative care services. By improving communication between primary and
      specialist palliative care, the programme should contribute substantially to
      improved care of the dying at home.

PMID- 14594155
TI  - Palliative day care: what does it cost to run a centre and does attendance affect
      use of other services?
AB  - AIM: To describe the cost of palliative day care (PDC), assessing the value of
      all resources whether paid for or not. To examine different patterns of resource
      use resulting from attending PDC. METHODS: Five PDC centres in southern England
      provided detailed cost and resource use data, both paid and unpaid for. The PDC
      group were consecutive new referrals to a PDC centre who were well enough to be
      interviewed. The comparison group were recruited from home care teams. Data were
      collected at baseline, six to eight weeks and 12-15 weeks, on health and social
      care utilization in the month prior to interview. Data were divided into cohorts
      based on time from first interview to death and analysed separately. MAIN
      OUTCOMES: Annual cost of running a day care centre, and cost per patient per day.
      Use of all health and social care resources over time, stratified by time from
      death. Comparison of health and social care by stage of illness, and by PDC
      attendance. RESULTS: PDC cost around pound 54 per person per day in 1999, rising
      to pound 75 including unpaid resources. 145 patients had data on health and
      social care use. The patterns of care showed that, overall, patients accessed few
      services other than PDC. Comparison group patients did not access similar
      services elsewhere. PDC might substitute home nursing and GP care for patients
      who attend PDC at least three months before death but this data is not
      conclusive. Inpatient care was negligible for both groups. CONCLUSIONS: A full
      economic evaluation could not be undertaken without robust evidence of the
      effectiveness of PDC. PDC centres made use of resources that were not paid for
      and shared resources with inpatient units, reducing costs. Service use was
      different for patients who attended compared with patients who did not. Similar
      services were not accessed elsewhere in the community; PDC does not appear to
      replicate other services for this group of patients.

PMID- 14594156
TI  - Anti-Hu antibodies may indicate a positive response to chemotherapy in
      paraneoplastic syndrome secondary to small cell lung cancer.
AB  - Paraneoplastic encephalomyelitis (PEM) is a form of neurological dysfunction
      caused by the remote effect of small cell lung cancer (SCLC) on the brain. In
      certain cases it is associated with the presence of Anti-Hu antibodies. Up to 65%
      of patients with SCLC and PEM, who have Anti-Hu antibodies present, die of
      neurological complications rather than tumour progression. Chemotherapy is not
      believed to be beneficial. We describe a 58-year-old lady who was bed-bound and
      significantly disabled from paraneoplastic cerebellar degeneration. Her serology
      confirmed the presence of Anti-Hu antibodies and SCLC was confirmed at
      bronchoscopy. Following six courses of chemotherapy her neurological symptoms
      have remarkably improved, both subjectively and objectively, such that she is now
      independently mobile with a walking frame. Her tumour is still evident on
      bronchoscopy. We suggest that people with SCLC who are significantly disabled by
      neurological symptoms, should be tested for serum anti-neuronal antibodies and if
      Anti-Hu antibody positive, anti-neoplastic treatment should be considered despite
      poor performance status.

PMID- 14594157
TI  - Can medical education extend palliative care?

PMID- 14594158
TI  - An alternative low-dose ad libitum schedule for conversion of other opioids to
      methadone.

PMID- 14594159
TI  - Palliative home care and dying at home is an option for patients living alone.

PMID- 14594160
TI  - Glucocorticoids in palliative medicine: is osteoporosis a problem?

PMID- 14594161
TI  - GPs' experiences of palliative care.

PMID- 14594162
TI  - Checking the facts.

PMID- 14594163
TI  - Insurance cover for research in independent hospices.

PMID- 14594164
TI  - Motor neurone disease and unexpected death: implications for CPR policy.

PMID- 14594165
TI  - Euthanasia: on slippery slopes and vulnerable patients.

PMID- 14594166
TI  - Concepts and definitions: a source of confusion in the euthanasia debate.

PMID- 14594167
TI  - Should the dose of growth hormone be increased during the growth spurt of
      children with isolated growth hormone deficiency?

PMID- 14594168
TI  - Management of adrenal crisis--how should glucocorticoids be administered?

PMID- 14594169
TI  - Rectal hydrocortisone during vomiting in children with adrenal insufficiency.
AB  - AIM: To evaluate rectal hydrocortisone as an emergency glucocorticoid replacement
      therapy in adrenal insufficient children. METHODS: A parental questionnaire
      evaluated preferred treatment, problems or benefits of i.m. and rectal
      hydrocortisone, frequency and indications for administration and who administered
      treatment. Admissions of children with adrenal insufficiency were monitored.
      RESULTS: There were 39/52 families who responded to the questionnaire. 93%
      (26/28) preferred rectal hydrocortisone. Parents or children who previously
      received emergency treatment from a doctor now self-administered rectal
      hydrocortisone. The cost of suppositories and i.m. hydrocortisone is similar;
      however, storage of suppositories was inconvenient. One girl presented with
      pneumonia and collapse despite rectal hydrocortisone and a hydrocortisone level
      at admission of >2000 nmol/l with normal electrolytes. CONCLUSIONS: Rectal
      hydrocortisone is an acceptable and safe emergency therapy. We still advise i.m.
      hydrocortisone if rectal administration is not possible or with suppository
      extrusion.

PMID- 14594170
TI  - Comparison of low and high dose of vitamin D treatment in nutritional vitamin D
      deficiency rickets.
AB  - In this study, we compared three different therapy modes (150,000 IU, 300,000 IU,
      and 600,000 IU vitamin D p.o.) in infants with nutritional vitamin D deficiency
      rickets (VDR). Our purpose was to determine the most effective dosage of vitamin
      D with least side effects for treating VDR. The study included 56 patients, 3-36
      months of age, with nutritional VDR and 20 age-matched control infants. In all
      infants, serum calcium, phosphorus, alkaline phosphatase, magnesium, serum 25
      hydroxycholecalciferol, plasma intact parathormone levels and urinary Ca/creatine
      ratio were determined. Of 56 patients, 52 were able to be followed long-term.
      These patients were reexamined on the 3rd day, 7-10th day, and 25-30th day after
      treatment. On the 30th day post-treatment, we did not find any difference between
      the doses in the improvement of rickets. However, hypercalcemia was present in
      eight infants who had been administered 300,000 IU (two infants) and 600,000 IU
      (six infants) of vitamin D. In conclusion, our findings showed that 150,000 IU or
      300,000 IU of vitamin D was adequate in the treatment of VDR, but 600,000 IU of
      vitamin D may carry the risk of hypercalcemia.

PMID- 14594171
TI  - Autoimmune thyroid dysfunction in children with type 1 diabetes mellitus:
      screening guidelines based on a retrospective analysis.
AB  - Individuals with type 1 diabetes mellitus (DM1) have an increased risk of
      developing autoimmune thyroid dysfunction (AITD). We measured the prevalence of
      AITD in a pediatric DM1 population in order to examine the best combination of
      markers for predicting the development of AITD. A database of 1,254 patients with
      DM1 under 21 years of age was retrospectively screened for abnormalities in
      antithyroglobulin antibody (ATA), thyroid peroxidase antibody (TPO) and thyroid
      stimulating hormone (TSH). Charts on all 134 who had any of these serologic
      abnormalities were reviewed. 4.2% of the DM1 population was clinically diagnosed
      with AITD. Thirty-nine percent of the AITD diagnoses came within 1 year of DM1
      diagnosis. Based upon evidence-based medicine statistics, TPO and TSH
      measurements are the most efficient and cost-effective combination of screening
      tests for AITD prediction and detection. The positive predictive value (of TPO
      and TSH) is 90%, with a positive likelihood ratio of 131.

PMID- 14594172
TI  - Sexual dimorphism in the synchrony of joint growth hormone and cortisol dynamics
      in children with classic 21-hydroxylase deficiency.
AB  - In humans, growth hormone (GH) and cortisol are secreted in a pulsatile fashion
      and a mutual bidirectional interaction between the GH/insulin-like growth factor
      (IGF)-I axis and hypothalamic-pituitary-adrenal (HPA) axis has been established.
      Classic congenital adrenal hyperplasia (CAH) is characterized by a defect in the
      synthesis of glucocorticoids and often mineralocorticoids, and adrenal
      hyperandrogenism. In view of the sexually dimorphic pattern in GH secretion, we
      investigated the GH-cortisol bihormonal secretory dynamics in male and female
      children with classic CAH. Thirty-eight children with classic 21-hydroxylase
      deficiency (M: 13, F: 25; age range: 6.1-18.8 yr) were studied prospectively.
      Serum GH and cortisol concentrations were determined at 20 min intervals for 24
      hours. The irregularity of GH and cortisol pattern was assessed using approximate
      entropy (ApEn), a scale- and model-independent statistic. The synchrony of joint
      GH-cortisol dynamics was quantified using the cross-ApEn statistic. Cross
      correlation analysis of GH and cortisol concentrations was computed at various
      time lags covering the 24-h period. There was no gender difference in mean 24
      hour serum GH (males vs females: 5.25 +/- 4.72 vs 4.44 +/- 2.64 mIU/l) or
      cortisol (156.2 +/- 44.6 vs 172.0 +/- 58.5 nmol/l) concentrations. For GH, ApEn
      values were significantly higher in females (0.66 +/- 0.14) than in males (0.53
      +/- 0.16) (p = 0.009). No difference in cortisol ApEn values was noted between
      sexes (0.53 +/- 0.21 vs 0.54 +/- 0.12). Cross-ApEn values of paired GH-cortisol,
      with cortisol leading GH, were significantly higher in females (0.94 +/- 0.14)
      than in males (0.83 +/- 0.20) (p = 0.03). These findings suggest that females
      with classic 21-hydroxylase deficiency have a more irregular pattern of GH
      secretion and a more asynchronous joint GH and cortisol dynamics than their male
      counterparts.

PMID- 14594173
TI  - Thyroid function tests in preterm infants born to preeclamptic mothers with
      placental insufficiency.
AB  - OBJECTIVE: Since preeclampsia causes placental insufficiency, it can be
      hypothesized that it decreases placental passage of thyroxine (T4) from mother to
      infant and thus may deepen the transient hypothyroxinemia seen in preterm infants
      after birth. The aim of this study was to compare thyroid function tests of
      preterm infants born to preeclamptic mothers with placental insufficiency with
      preterm infants born to mothers without placental insufficiency. METHODS: Thirty
      one preterm infants born to preeclamptic mothers with placental insufficiency
      were included in the study (group I) and 31 preterm infants born to mothers
      without placental insufficiency were included as the control group (group II).
      Thyroid hormone levels were assayed from blood samples obtained from the women
      before birth and thereafter from the infants at delivery (cord) and on the 1st,
      3rd, 7th, and 21st days of life. RESULTS: Cord blood triiodothyronine (T3), free
      T3 (FT3) and free thyroxine (FT4) levels in group I were lower than in group II,
      whereas thyrotropin (TSH) and thyroxine binding globulin (TBG) levels were
      higher. No statistical difference in hormone levels studied at postnatal 1st,
      3rd, 7th, and 21st day was found between the two groups. CONCLUSION: Low levels
      of thyroid hormones and high level of TSH in cord blood in premature infants born
      to preeclamptic mothers with placental insufficiency suggest intrauterine
      hypothyroidism. Increase in TSH and thyroid hormone concentrations after birth
      reveal that the hypothalamic-pituitary-thyroid axis is intact.

PMID- 14594174
TI  - Growth hormone treatment in Aarskog syndrome: analysis of the KIGS (Pharmacia
      International Growth Database) data.
AB  - Aarskog syndrome is an X-linked disorder characterized by faciogenital dysplasia
      and short stature. The present study set out to determine the effect of growth
      hormone (GH) therapy in patients with Aarskog syndrome enrolled in KIGS--the
      Pharmacia International Growth Database. Twenty-one patients (20 males) were
      evaluated. Median age at start of treatment was 8.3 years (10-90th percentiles,
      5.1-14.1 years) and median height SDS was -2.8 (10-90th percentiles, -2.1 to 
      3.7). The median dose of GH was 0.22 mg/kg/week (10-90th percentiles, 0.15-0.30
      mg/kg/week) given at a median frequency of six (4-7) times per week. Prepubertal
      patients were followed longitudinally for 1 year (n = 13) or 3 years (n = 7).
      After 1 year, the median height SDS had improved from -2.8 to -2.3 in 13
      patients. After 3 years, height SDS had improved significantly (p <0.05) to -1.8
      (10-90th percentiles, -2.1 to -1.1) in the seven patients. No adverse events were
      noted. Although final height data for these patients are still awaited, the
      present results support the use of GH to promote growth in children with Aarskog
      syndrome.

PMID- 14594175
TI  - Isolated growth hormone deficiency in Chilean patients: clinical and molecular
      analysis.
AB  - Isolated growth hormone deficiency (IGHD) is a disorder that leads to short
      stature. It has been classified into types IA, IB, II and III. GH gene mutations
      and growth hormone releasing hormone (GHRH) receptor gene mutations have been
      described in patients with IGHD. We report here a clinical and molecular study of
      27 Chilean patients with IGHD. We performed GH stimulation tests with GHRH and
      GHRP, and segregation and molecular analysis of the GH, GHRH and GHRH receptor
      genes. We describe four patients with IGHD IA bearing a 7 kb mutation (13%), and
      two IGHD II patients who showed two different splice site point mutations (6.8%).
      In 21 patients, we did not find a mutation in any of the three genes examined.
      These results led us to conclude that the molecular causes of IGHD involve other
      genes besides those analyzed in this report, as has been reported previously in
      patients of different ethnic origins.

PMID- 14594176
TI  - Y chromosome sequences in Turner's syndrome: association with virilization and
      gonadoblastoma.
AB  - The presence of Y chromosome fragments in patients with Turner's syndrome is
      known to increase the risk of gonadoblastoma and virilization. Y chromosome
      material is detected in up to 6% of patients with Turner's syndrome by karyotype.
      By DNA analysis, Y chromosome sequences have been reported in 0-60% of patients.
      The putative gonadoblastoma gene has been mapped to the pericentromeric region of
      the Y chromosome increasing the interest in studying these sequences. AIMS: 1. To
      determine the frequency of occult Y chromosome sequences in patients with
      Turner's syndrome. 2. To analyze the clinical implications of Y sequences
      detected by karyotype and occult Y sequences. STUDY DESIGN: Cross-sectional study
      of 58 patients with Turner's syndrome (30 45,X; two with structural anomalies; 26
      mosaic [two of whom were 45,X/46,XY]). SRY, TSPY and DYZ3 sequences were
      amplified by PCR using genomic DNA from peripheral blood. RESULTS: All three Y
      chromosome sequences were found in one out of 56 patients whose karyotype was not
      suggestive of having Y chromosome material and in one patient with 45,X/46,Xr(X)
      karyotype. The patients with the ring chromosome and 45,X/46,XY karyotype
      underwent surgery and were found to have a gonadoblastoma and dysgerminoma. The
      four patients with Y chromosome material had non-virilized female genitalia.
      CONCLUSIONS: Analysis by PCR was more sensitive in detecting Y chromosome
      sequences than conventional karyotype. The presence of Y material was not
      associated with virilization. We confirmed the association of Y fragments and
      gonadoblastoma at an early age.

PMID- 14594177
TI  - Growth, growth velocity and adult height in Mexican girls with Turner's syndrome.
AB  - This was a prospective, longitudinal and descriptive study of 117 Mexican girls
      with Turner's syndrome (TS) followed from diagnosis to 18 years old. Height,
      weight and growth velocity were evaluated every 4-6 months, and bone age was
      assessed annually. Adult height was reached in 87 girls. All the girls were
      treated during 1 year with conjugated estrogens at bone age of 12 years, and
      subsequently with mixed estrogen/progestogen. Growth retardation in girls with TS
      is apparent at birth (2.7 +/- 0.9 kg and 46.3 +/- 5.0 cm) and in childhood, but
      becomes most marked when puberty would normally occur. Mean growth velocity was
      less than 25th percentile from birth to 2 years, less than 10th percentile
      between 3-9 years, and less than 3rd percentile from 10 to 18 years of age. Final
      adult height was 136.9 +/- 5.5 cm, but it is affected by the particular
      karyotype: 46,Xi(Xq): 134.5 cm, 45,XO: 137.3 cm, and 45XO/46,XX: 139 cm.

PMID- 14594178
TI  - Urinary deoxypyridinoline, serum osteocalcin and bone mineral density in girls
      with Turner's syndrome.

PMID- 14594179
TI  - Laparoscopically performed gastric banding in a 13 year-old girl with morbid
      obesity and end stage renal insufficiency allows lifesaving weight loss and
      hemodialysis.
AB  - OBJECTIVE: In adults, laparoscopic gastric banding is applied to treat morbid
      obesity, usually in combination with dietary and psychological intervention and
      increased physical exercise. However, little information is available on gastric
      banding in children. PATIENT AND METHODS: The 13 year-old girl suffered from end
      stage renal failure. Complications with hemodialysis catheters due to her
      extensive subcutaneous fat pads led to a life-threatening deterioration of her
      uremia. Intensive conventional schedules for weight reduction failed to be
      effective, so the morbidly obese girl (body mass index [BMI] 37.7 kg/m2, +3.6
      standard deviation score [SDS]) underwent laparoscopic gastric banding at the age
      of 13 years after informed parental consent was obtained. RESULTS: After
      laparoscopic gastric banding there was a notable weight loss of 14 kg and an
      eventually adequate hemodialysis was possible. Total weight loss of the now 15
      year-old girl was 24 kg (present BMI 28.3 kg/m2, +2.2 SDS). CONCLUSION: Even in
      childhood, laparoscopic gastric banding may be considered in cases of morbid
      obesity in critically ill patients.

PMID- 14594180
TI  - A novel mutation of the growth hormone receptor gene (GHR) in a Chinese girl with
      Laron syndrome.
AB  - Laron syndrome, also known as growth hormone insensitivity syndrome (GHIS), is an
      autosomal recessive genetic disorder associated with severe postnatal growth
      failure, and normal and/or elevated growth hormone. This disease is frequently
      caused by a point mutation in the growth hormone receptor gene (GHR). Here, we
      identified a novel homozygous substitution mutation (E42K: GAG-->AAG at codon 42
      cDNA) of the GHR gene in a Chinese girl with Laron syndrome. This mutation was
      predicted to impair the GHR binding affinity to human growth hormone (hGH), and
      was responsible for low levels of insulin-like growth factor (IGF)-I, IGF binding
      protein (IGFBP)-3, and GH binding protein (GHBP) in serum.

PMID- 14594181
TI  - Reversible cardiomyopathy in paediatric Addison's disease--a cautionary tale.
AB  - A 13 year-old girl with clinical features of Addison's disease developed acute
      cardiac failure after initiation of treatment and after initial clinical
      improvement. Large doses of i.v. hydrocortisone and oral fludrocortisone, in
      addition to inotropic and ventilatory support, were required to achieve
      cardiovascular stability. The cardiomyopathy improved over one week and her
      condition then remained stable on oral glucocorticoid and mineralocorticoid
      replacement therapy. Reversible cardiomyopathy is a rare and potentially life
      threatening complication of Addison's disease. The second reported paediatric
      patient is presented, the only one reported to require ventilatory support.

PMID- 14594183
TI  - Swedish norms for the Harvard Group Scale of Hypnotic Susceptibility, Form A.
AB  - This article examines the norms for a Swedish adaptation of the Harvard Group
      Scale of Hypnotic Susceptibility, Form A (HGSHS:A) (Shor & Orne, 1962). In total,
      291 subjects (199 females and 92 males) participated in the study. Comparisons
      are made between the Swedish sample and reference samples, which include English
      versions of the HGSHS:A from the United States and Australia, as well as 5
      translated versions from Italy, Finland, Denmark, Spain, and Germany. In the
      Swedish sample, females scored significantly higher than males. Generally,
      however, the normative data from the Swedish sample are congruent with the
      reference samples and therefore can be used as a tool for initial screening of
      hypnotic susceptibility in Sweden.

PMID- 14594182
TI  - Steroid 5alpha-reductase 2 deficiency in two generations of a non-consanguineous
      Chinese family.
AB  - We report a Chinese family in which two family members were diagnosed to have
      steroid 5alpha-reductase 2 deficiency. The proband was an 8 year-old boy
      presenting with isolated micropenis. Mutational analysis revealed a homozygous
      mutation in exon 4 of the SRD5A2 gene, changing codon 227 from CGA to CAA, i.e.
      R227Q. The paternal granduncle of the proband has incomplete virilization in
      adulthood. Besides having the mutation R227Q, he has another mutation in exon 5
      of the SRD5A2 gene, changing codon 246 from CGG to CAG, i.e. R246Q. To our
      knowledge, this is the first reported Chinese family diagnosed with steroid
      5alpha-reductase 2 deficiency with identified molecular defects.

PMID- 14594184
TI  - Adverse short-term effects of attention-control treatment on hypnotizability: a
      challenge in designing controlled hypnosis trials.
AB  - Characteristics of patients in test and attention-control groups should be
      comparable and be unaffected by the intervention to be tested in clinical trials.
      The authors assessed whether this is the case for measures of hypnotizability in
      the postoperative period. One hundred and forty-six patients undergoing
      percutaneous peripheral vascular or renal interventions were randomized into 2
      groups. One group received structured empathic attention during their procedures;
      the other was guided to self-hypnotic relaxation. Hypnotizability was assessed
      postoperatively by the Hypnotic Induction Profile. The eye-roll scores, which
      measure the biological hypnotic potential, were not significantly different, but
      the average induction scores, which measure the expression of the hypnotic
      performance, were significantly lower in the attention group than the hypnosis
      group (4.9 vs. 5.9). The authors conclude that patients who were aided by an
      external focus intraoperatively are postoperatively less able or willing to
      follow suggestions measuring hypnotizability than patients who had guidance to
      self-hypnotic relaxation.

PMID- 14594185
TI  - Beliefs about hypnosis: popular beliefs, misconceptions, and the importance of
      experience.
AB  - Contemporary views and opinions about hypnosis were sampled with a modified
      version of McConkey's Opinions About Hypnosis (OAH) scale. The OAH was
      administered at 2 different times, 1 month apart, to 276 undergraduate students.
      Approximately half of the participants completed the Harvard Group Scale of
      Hypnotic Susceptibility, Form A, between the survey sessions. Results indicated
      that the experience of being hypnotized modified a majority of the opinions
      sampled, with participants expressing less stereotypic views about hypnosis after
      being hypnotized. Expressed opinions and beliefs about hypnosis failed to
      meaningfully correlate with hypnotizability scores.

PMID- 14594186
TI  - Hypnotizability and posttraumatic stress disorder: a prospective study.
AB  - Although there is converging evidence that posttraumatic stress disorder (PTSD)
      is associated with higher levels of hypnotizability, there are no studies
      concerning the stability of hypnotizability levels following trauma. Acutely
      traumatized participants with acute stress disorder (N = 45) were administered
      the Stanford Hypnotic Clinical Scale (SHCS) within 4 weeks of their trauma.
      Participants were subsequently administered a brief cognitive-behavior therapy
      program. Six months after treatment, participants were re-assessed with the SHCS.
      Although SHCS scores were generally stable (r = .47), two thirds of participants
      responded differently across the 2 assessments. Increased SHCS scores at the
      second assessment were correlated with elevated PTSD avoidance scores. This
      finding suggests that elevated hypnotizability in PTSD populations may not be
      entirely stable and may be associated with specific PTSD responses.

PMID- 14594187
TI  - Could empathy be a predictor of hypnotic ability?
AB  - This study examined whether trait empathy is related to hypnotic ability and
      absorption. Sixty-four graduate students and mental health professionals
      completed the Harvard Group Scale of Hypnotic Susceptibility, Form A; the Davis
      Interpersonal Reactivity Index; and the Tellegen Absorption Scale as measures of
      hypnotic ability, empathy, and absorption. Correlation analysis determined that
      statistically significant relationships exist between empathy and hypnotic
      ability (r = .41); empathy and absorption (r = .43); and absorption and hypnotic
      ability (r = .31). The results also indicate that empathy and absorption are both
      predictors of hypnotic ability, although absorption does not appear to contribute
      a statistically significant amount of the explained variance in hypnotizability
      that is independent of empathy. It may be that the conceptual ground shared by
      both empathy and absorption is what predicts hypnotic ability.

PMID- 14594188
TI  - Hypnosis, attention, and time cognition.
AB  - This study examined the influence of hypnotic susceptibility (high vs. low),
      hypnotic condition (hypnotic vs. nonhypnotic), and attentional demands (high vs.
      low) on the verbal estimates (N = 510 undergraduates) of 30- and 60-second time
      intervals under both prospective (aware of timing) and retrospective (unaware of
      timing) paradigms. It was expected that prospective judgments would be greater
      than retrospective judgments across all factors. Consistent with existing
      literature, strong support was found for this hypothesis. Hypotheses generated
      within the trait-state paradigm were not supported. No effects were found for
      hypnotic susceptibility in any form. Partial support was found for the
      sociocognitive model. The hypnotic context, independent of level of
      susceptibility, apparently utilizes the attentional resources of participants and
      as a by-product leads to underestimation of time. Longer time intervals (60 s)
      were also underestimated in comparison to shorter intervals (30 s).

PMID- 14594190
TI  - The effects of whole body vibration on humans: dangerous or advantageous?
AB  - The effects of whole body vibration (WBV) have been studied extensively in
      occupational medicine. In particular, it has been shown that when the body
      undergoes chronically to whole body vibrations spinal degeneration is likely to
      be one of the deleterious outcomes. Low back pain has been shown to be the
      leading major cause of industrial disability in the population under the age of
      45 years and has been linked to whole body vibration exposure encountered in some
      industrial settings. Whole body vibration has been recently purposed as an
      exercise intervention suggesting its effectiveness in increasing force-generating
      capacity in lower limbs and low back. It has also been reported to be an
      effective non-pharmacological intervention for patients with low back pain.
      Relatively short exposure to whole body vibration has been also shown to increase
      the serum levels of testosterone and growth hormone. The combined effects on the
      neuromuscular system and endocrine system seem to suggest its effectiveness as a
      therapeutic approach for sarcopenia and possibly osteoporosis. Due to the danger
      of long-term exposure to whole body vibration, it is important to develop safe
      exercise protocols in order to determine exercise programs for different
      populations.

PMID- 14594189
TI  - Pathophysiological aspects of cellular pyridine nucleotide metabolism: focus on
      the vascular endothelium. Review.
AB  - In recent years, pyridine nucleotides NAD(H) and NADP(H) have been established as
      an important molecules in physiological and pathophysiological signaling and cell
      injury pathways. Protein modification is catalyzed by ADP-ribosyl transferases
      that attach the ADP-ribose moiety of NAD+ to specific aminoacid residues of the
      acceptor proteins, with significant changes in the function of these acceptors.
      Mono(ADP-ribosyl)ation reactions have been implicated to play a role both in
      physiological responses and in cellular responses to bacterial toxins. Cyclic ADP
      ribose formation also utilizes NAD+ and primarily serves as physiological, signal
      transduction mechanisms regulating intracellular calcium homeostasis. In
      pathophysiological conditions associated with oxidative stress (such as various
      forms of inflammation and reperfusion injury), activation of the nuclear enzyme
      poly(ADP-ribose) polymerase (PARP) occurs, with subsequent, substantial fall in
      cellular NAD+ and ATP levels, which can determine the viability and function of
      the affected cells. In addition, NADPH oxidases can significantly affect the
      balance and fate of NAD+ and NADP in oxidatively stressed cells and can
      facilitate the generation of various positive feedback cycles of injury. Under
      severe oxidant conditions, direct oxidative damage to NAD+ has also been
      reported. The current review focuses on PARP and on NADPH oxidases, as
      pathophysiologically relevant factors in creating disturbances in the cellular
      pyridine nucleotide balance. A separate section describes how these mechanisms
      apply to the pathogenesis of endothelial cell injury in selected cardiovascular
      pathophysiological conditions.

PMID- 14594191
TI  - Endorphin content of white blood cells and peritoneal cells in neonatally
      benzpyrene treated adult rats.
AB  - White blood cells of rats (lymphocytes, monocytes, macrophages, granulocytes and
      mast cells) contain beta-endorphin. Two months after a single neonatal benzpyrene
      treatment (imprinting) there is an elevated level of immunoreactive endorphin in
      the blood and peritoneal cells of female animals and blood cells of males. The
      endorphin content decreased in the peritoneal cells of males. In the blood, the
      granulocytes of female, and the lymphocytes of male rats contained the highest
      amount of endorphin. In the peritoneal fluid also the granulocytes of females
      contained the highest amount of endorphin, in contrast to males, where the
      endorphin content of cells decreased and the lowest level of it was present in
      the lymphocytes. The experiments justify that benzpyrene treatment can durably
      influence endorphin levels of white blood cells and gives new data to the already
      known lifelong health destroying effects of perinatal benzpyrene exposition
      (alterations of hormone receptor binding capacity and sexual behavior).

PMID- 14594192
TI  - Plasma 6beta-hydroxycortisol measurements for assessing altered hepatic drug
      metabolizing enzyme activity.
AB  - To study the usefulness of 6beta-hydroxycortisol (6betaOHF) measurements for
      assessing hepatic drug metabolizing enzyme activity, plasma 6betaOHF and cortisol
      were measured in 22 patients with alcoholic liver disease after at least 2 weeks
      of alcohol abstinence, in 5 patients with severe Cushing's syndrome and in 12
      healthy non-drinker subjects. Blood samples were drawn under resting conditions
      during midnight, in the morning at 0800 h, after a 1-mg overnight dexamethasone
      test and after ACTH administration. Plasma cortisol and 6betaOHF were determined
      with radioimmunoassay. In patients with alcoholic liver disease, the plasma
      cortisol levels at midnight and 0800 h, as well as after the administration of
      dexamethasone and ACTH were not different from corresponding values measured in
      non-drinker controls. In addition, these patients with alcoholic liver disease
      had similar plasma 6betaOHF levels at midnight, 0800 h and after dexamethasone
      administration as compared to corresponding values in controls. By contrast, ACTH
      administration in patients with alcoholic liver disease resulted in a
      significantly (p<0.05) larger increase of plasma 6betaOHF (from 106 +/- 22 to
      1102 +/- 106 ng/dl, mean +/- SE) as compared to that found in controls (from 74
      +/- 3 to 337 +/- 76 ng/dl). The markedly increased 6betaOHF response to ACTH
      administration in patients with alcoholic liver disease was similar to that
      measured in patients with severe Cushing's syndrome, in whom increased and non
      suppressible plasma cortisol levels were accompanied by markedly elevated plasma
      6betaOHF levels. These results indicate that alcohol abstinence in patients with
      alcoholic liver disease is associated with an exaggerated 6betaOHF response to
      ACTH and that this abnormality may prove to be a clinically useful parameter for
      a sensitive detection of altered drug metabolism present in these patients.

PMID- 14594193
TI  - Relationship of anthropometrical, physiological and motor attributes to sport
      specific skills.
AB  - The purpose of this pilot study was to investigate the importance of the
      athlete's motor capabilities in success in sport. More precisely, the association
      of anthropometrical and physiological attributes, as well as motor abilities of
      elite basketball players with play elements of basketball. The subjects were
      seven elite basketball players. At the end of the competitive season, the
      anthropometrical and physiological features were measured to establish the
      physical fitness of the subjects. Both general and sport-specific motor tests
      were done. The coach estimated the performance of each player during the games of
      the competitive season. The coach's data sheet incorporated 14 parameters of the
      game. Regression analyses indicated significant correlation between certain
      variables of the laboratory tests and the data of the coach's estimation
      statistics. Knowing these relationships provides us with valuable predictive
      information about player's capabilities in sport.

PMID- 14594194
TI  - The effects of adrenalectomy on the harderian gland of the Wistar albino rats.
AB  - Harderian glands of the Wistar albino rats normal and adrenalectomized were
      investigated by light microscopy. In normal, these glands have a tubuloalveolar
      structure. The gland is located in the medio posterior aspect of the orbit. It is
      lobulated and appears homogeneous in colour and texture. Harderian gland consist
      of tubules with wide lumina lined by a single layer of columnar epithelial cells
      surrounded by myoepithelial cells within their basal lamina. It contains
      porphyrin pigment which is stored as solid intraluminal deposits. The glandular
      epithelium possesses two cell types, termed A and B. Type A cells are more
      numerous. The single excretory duct of the gland is directly continuous with
      endpieces at the hilus and opens nasally and ventrally to the third eyelid. The
      excretory duct is accompanied by many acini of small serous glands around it. The
      tubuloalveoli of the gland is not divided into lobules. There is no branched duct
      system within the gland. The secretion seems to be associated with porphyrins, is
      essentially released by exocytosis, but holocrine secretion also occurs. The
      single excretory duct is lined by a stratified epithelium. The gland is
      surrounded by a collagenous capsule. The adrenalectomy, caused degenerative
      changes in the glands. Epithelial height was lower than in normal gland
      epithelium. Most of the acini were completely disorganised. The acinar lumina
      were filled with porphyrin debris. The results suggest that rat harderian glands
      are sensitive to adrenal androgen changes in both male and female rats.

PMID- 14594195
TI  - The effect of mebudipine and dibudipine, two new Ca2+ channel blockers, in
      comparison with nifedipine on Ca2+ spikes of F1 neuronal soma membrane in Helix
      aspersa.
AB  - Mebudipine and dibudipine are two new dihydropyridine (DHP) Ca2+ channel blockers
      that have been synthesized by Mahmoudian et al. (1997). In previous studies, they
      showed considerable relaxant effect on vascular and ileal smooth muscles. These
      two compounds also reduced the contraction force of rat left atrium (20, 22). In
      the present study, we attempted to compare the inhibitory actions of these new
      DHPs and nifedipine on the high threshold Ca2+ spikes of F1 neuronal soma
      membrane in the subesophageal ganglia of Helix aspersa, using current-clamp
      method. At a concentration of 1 microM, two new DHP compounds (mebudipine and
      dibudipine) were tested for their L-type Ca2+ channel blocker activity. Both
      compounds reversibly reduced the peak amplitude of action potential and after
      hyperpolarization potential and markedly decreased the duration of Ca2+ spikes.
      The most potent of these DHPs was mebudipine. Neither the two new DHPs nor
      nifedipine changed the resting membrane potential in a statistically significant
      way.

PMID- 14594197
TI  - Association of melatonin secretion with seasonal luminosity in human subjects.

PMID- 14594196
TI  - Effect of diazepam treatment on metabolic indices in trained and untrained rats.
AB  - Exercise training, like diazepam, is commonly employed as a means of reducing
      anxiety. Both diazepam and exercise training have been shown to modify
      carbohydrate and lipid metabolism as well as influence calcium metabolism in
      skeletal muscle. As receptor binding and thereby efficacy of diazepam has been
      demonstrated to be modulated by the lipid environment of the receptor, and
      changes in calcium levels can affect a number of intracellular signalling
      pathways, we sought to determine if the interaction of both chronic diazepam and
      exercise training would modify selected metabolic indices in an animal model. For
      this purpose, muscle and liver glycogen, blood glucose and plasma free fatty
      acids (FFA) were measured in sedentary, exercise trained and exercise trained,
      acutely exhausted animals. Alterations in lipid and carbohydrate metabolism were
      observed in all experimental groups. Diazepam treatment alone exerts metabolic
      consequences, such as elevated muscle glycogen and plasma FFA and depressed blood
      glucose levels, which are similar to those observed with exercise training. When
      animals are acutely exercised to exhaustion, however, differences appear,
      including a reduced rise in plasma FFA, which suggests that long-term diazepam
      treatment does influence exercise metabolism, possibly as a result of effects on
      the sympatho-adrenal system.

PMID- 14594198
TI  - Diet and mental health in the Arctic: is diet an important risk factor for mental
      health in circumpolar peoples?--a review.
AB  - BACKGROUND: The people living in Arctic and Subarctic environments have adapted
      to cold temperatures, short growing seasons, and low precipitation, but their
      traditional ways are now changing due to increased contact with Western society.
      The rapid alteration of circumpolar cultures has led to generational changes in
      diet from traditional foods to the processed groceries common in modern stores.
      OBJECTIVES: Develop a link between changing traditional diets and mental health
      that may have substantial consequences for circumpolar peoples. METHODS: Review
      of English language literature pertaining to the northern circumpolar
      environments of the world that consist of the Arctic and Subarctic areas.
      Electronic resources such as ISI Web of Science and PubMed were utilized, using
      keywords such as arctic, circumpolar, diet, omega-3 fatty acids, mental health,
      seasonal affective disorder, and suicide. In addition, we used the cited
      references of obtained articles and the extensive University of Alaska Fairbanks
      library collections to identify additional publications that were not available
      from the electronic resources. The years covered were not restricted to any
      particular period, although 83% of the sources were published in the last 16
      years. CONCLUSION: The change in traditional diets has already led to increased
      health problems, such as obesity, cardiovascular disease, and diabetes, while the
      mental health of circumpolar peoples has also declined substantially during the
      same time period. The decline in mental health is characterized by increased
      rates of depression, seasonal affective disorder, anxiety, and suicide, that now
      often occur at higher rates than in lower-latitude populations. Studies in non
      circumpolar peoples have shown that diet can have profound effects on neuronal
      and brain development, function, and health. Therefore, we hypothesize that diet
      is an important risk factor for mental health in circumpolar peoples.

PMID- 14594199
TI  - Alterations in serum melatonin and sleep in individuals in a sub-arctic region
      from winter to spring.
AB  - METHODS: In a sub-arctic region at 69 degrees N, seven individuals with self
      reported insomnia during the 'dark period' and seven without, were followed with
      repeated measures of melatonin and questioned on ten different sleep variables,
      from the beginning of January to the vernal equinox in March. RESULTS: The
      distribution of melatonin over a 24-hour period (five time points) indicated an
      increase in melatonin levels in both groups in the middle of January and a
      decrease at the time of year when the sun first rises over the horizon (23rd-24th
      of January). Moreover, an indication of a delayed phase shift of melatonin
      secretion was found during the dark period, which returned to "normal" secretion
      during the night at the equinox in March. Individuals with sleep problems had a
      slower return to "normal" melatonin secretion than those without sleep problems.
      A positive correlation between morning tiredness and morning levels of melatonin
      was found among individuals with sleep disturbances, but not in controls.
      CONCLUSION: This study indicates changes in the internal circadian rhythm in
      humans at the end of the annual dark period of winter when there is a rapid
      increase in the number of hours of sunlight. For vulnerable individuals, the
      disturbance in sleep, and in particlar morning tiredness, lasts at least until
      the vernal equinox in March.

PMID- 14594200
TI  - Effect of the Antarctic environment on hormone levels and mood of Chinese
      expeditioners.
AB  - BACKGROUND: Serum thyroid hormones, plasma catecholamines and mood were examined
      in 10 male members of the 16th Chinese Antarctic Expedition who spent the 2000
      austral winter at Great Wall Station. STUDY DESIGN: Samples were taken prior to
      deployment to Antarctica (December, 1999) and upon return to China 54 weeks later
      (December, 2000). The expeditioners also completed the Profile of Mood States
      (POMS) each month over an 8-month period (April through November, 2000). RESULTS:
      There was a significant decrease in levels of serum total thyroxine (p < 0.01)
      and plasma epinephrine (p < 0.05), and a significant increase in serum TSH (p <
      0.01). With the exception of a significant decline in level of vigor (p = 0.008),
      there were no significant changes in mood throughout the expedition. Low levels
      of pre- and post-deployment total triiodothyronine and high levels of TSH were
      significantly associated with high levels of tension-anxiety, depression, anger,
      confusion, and total mood disturbance at the beginning and end of winter. High
      levels of TSH were also significantly associated with high levels of fatigue (p <
      0.001), while low levels of total thyroxine were significantly associated with
      high levels of tension-anxiety (p < 0.001), depression (p < 0.05), and total mood
      disturbance (p < 0.05). Low levels of dopamine were significantly associated with
      high levels of tension-anxiety (p < 0.05). An increase in anger during the
      austral winter was significantly associated with an increase in adrenaline during
      the expedition (p < 0.05). CONCLUSION: The increase in TSH, and its association
      with mood, is consistent with the polar T3 syndrome, while the absence of changes
      in free triiodothyronine and thyroxine may reflect characteristics of the
      environment, or racial/ethnic differences in psychophysiological, or socio
      cultural adaptation to circumpolar environments.

PMID- 14594201
TI  - Determinism, risk and safe driving behavior in northern Alberta, Canada.
AB  - INTRODUCTION: There is evidence that Alberta's rural north is over-represented in
      the Canadian province's overall traffic fatality rate, even after weather, travel
      exposure and highway geometry are controlled for. OBJECTIVE: The objective of
      this study was to identify underlying reasons and rationales that northern
      citizens use to accommodate risk and driving behavior. METHODS: A total of 82
      individuals participated in 13 focus groups, each with between 5 and 10
      participants. Eight focus groups were conducted with general drivers and five
      with service professionals in five different Alberta locations. Discussions
      centered on a series of questions that were designed to elicit insight into
      general characteristics of the participants' world-view and featured two
      categories of questions, including dimensions of belief systems and driver
      characteristics and behavior. RESULTS: Although much of the discussions focused
      on freedom of choice, over half of the interviewees cited determinism as a key
      feature of responsibility. Three versions of determinism were emphasized as key
      in roadway safety: religious determinism, 'universal' determinism (fatalism), and
      humanistic determinism. These observations highlighted peoples' perception of the
      likelihood of getting into traffic situations outside one's control. CONCLUSION:
      In order to maximize the effectiveness of traffic safety in the north,
      professionals need to take an approach which addresses not only safety issues,
      but also issues regarding responsibility and its links with behavior.

PMID- 14594202
TI  - Hair chromium concentration of northern Finns.
AB  - OBJECTIVES: The present study is a pilot project for the Finnish AMAP (Arctic
      Monitoring and Assessment Programme/Human Health) investigations. We examined the
      exposure of northern Finns to chromium (Cr), because analyses of this metal are
      not included in the AMAP, and local industry and industry throughout the Kola
      Peninsula may increase chromium fallout in Finnish Lapland. Chromium exposure and
      its temporal trend were estimated by analyzing hair of northern Finns collected
      in 1982 and 1991. METHODS: After washing the hair samples, chromium analyses were
      carried out in 1995 by a method developed by Salmela et al. (1981) and
      Kumpulainen et al. (1982). The Perkin-Elmer 5000 atomic absorption spectrometer
      used was equipped with a graphite furnace (HGA-400). RESULTS: Age showed no
      statistically significant correlation with Cr concentration in hair, but the hair
      concentration of Cr in men was higher than that in women, both among southern and
      northern Finns and Sami. CONCLUSIONS: Chromium levels in the hair of Finns and
      Sami were too low to result in any health hazard, however, exposure to chromium
      may have slightly increased during the 1990s.

PMID- 14594203
TI  - Growth in Greenland: development of body proportions and menarcheal age in
      Greenlandic children.
AB  - INTRODUCTION: No recent investigations of child growth in Greenland are
      available. Owing to the secular trend, earlier investigations are of limited
      clinical value. OBJECTIVES: For this reason, we studied the most important
      anthropometric measurements of school children in Maniitsoq, Greenland. METHODS:
      We recorded weight, standing height, sitting height, armspan and menarcheal age.
      After the exclusion of ten children, who were either suffering from conditions
      known to influence growth, or for whom some of the anthropometric data were
      lacking, 299 boys and 290 girls remained in the study. The 589 children were
      between 5-19 years old. RESULTS: In comparison with a similar study in Maniitsoq
      undertaken a little more than 30 years ago, 14-year old children in Maniitsoq
      have increased standing height by 10 cms, or even more. Up to the age of 14,
      Greenlandic boys followed the Danish curve for standing height, then flattened
      out to reach a final mean height about 7 cms below the Danish level. The girls'
      growth curve followed the Danish one only to the age of 11 years, then flattened
      out to a final height of 5 cms below the Danish level. A somewhat higher sitting
      height ratio was recorded for both sexes compared to Danish children. The mean
      menarcheal age was 12.64 years. CONCLUSION: During the course of 100 years,
      menarcheal age in Greenland has diminshed by three years, and is now 3 months
      below that in Denmark.

PMID- 14594204
TI  - Life span of people who died from cardiovascular diseases in Siberia: a
      comparative study of two populations.
AB  - OBJECTIVES: To assess associations between mean age at death from cardiovascular
      disease (myocardial infarction, acute heart failure, ischemic heart disease and
      stroke) and sex, education, socio-professional status, marital status, region of
      residence at birth, month and season of birth and of death in dependence of
      climatic conditions. DESIGN: A retrospective analysis of death certificates in
      two Siberian cities from 1971 to 1978 (Novosibirsk, south-western Siberia) and
      from 1968 to 1985 (Mirny, western Yakutia). METHODS: Analysis of variance, test
      for seasonality. RESULTS: A remarkable effect of birthplace on longevity was
      observed in Novosibirsk. West Russia-born decedents were older than their cause
      of-death-matched counterparts born in Siberia. In this city, men died at younger
      age in spring months compared to the rest of the year. In Mirny, an extreme
      northern town with a very harsh climate, the life span depended on the duration
      of living in this region prior to death. CONCLUSION: There was some difference
      among cardiovascular diagnoses and between the two cities. However, overall, the
      results offer some support for theories suggesting that early "imprinting" is
      responsible for the association between life span and region/season of birth.

PMID- 14594205
TI  - Maternal postnatal depression: causes and consequences.

PMID- 14594206
TI  - Confounding factors and seasonal depression.

PMID- 14594207
TI  - Amphibian regeneration and stem cells.
AB  - Larval and adult urodeles and anuran tadpoles readily regenerate their limbs via
      a process of histolysis and dedifferentiation of mature cells local to the
      amputation surface that accumulate under the wound epithelium as a blastema of
      stem cells. These stem cells require growth and trophic factors from the apical
      epidermal cap (AEC) and the nerves that re-innervate the blastema for their
      survival and proliferation. Members of the fibroblast growth factor (FGF) family
      synthesized by both AEC and nerves, and glial growth factor, substance P, and
      transferrin of nerves are suspected survival and proliferation factors. Stem
      cells derived from fibroblasts and muscle cells can transdifferentiate into other
      cell types during regeneration. The regeneration blastema is a self-organizing
      system based on positional information inherited from parent limb cells.
      Retinoids, which act through nuclear receptors, have been used in conjunction
      with assays for cell adhesivity to show that positional identity of blastema
      cells is encoded in the cell surface. These molecules are involved in the cell
      cell signaling network that re-establishes the original structural pattern of the
      limb. Other systems of interest that regenerate by histolysis and
      dedifferentiation of pigmented epithelial cells are the neural retina and lens.
      Members of the FGF family are also important to the regeneration of these
      structures. The mechanism of amphibian regeneration by dedifferentiation is of
      importance to the development of a regenerative medicine, since understanding
      this mechanism may offer insights into how we might chemically induce the
      regeneration of mammalian tissues.

PMID- 14594208
TI  - Existence of reserve quiescent stem cells in adults, from amphibians to humans.
AB  - Several theories have been proposed to explain the phenomenon of tissue
      restoration in amphibians and higher order animals. These theories include
      dedifferentiation of damaged tissues, transdifferentiation of lineage-committed
      stem cells, and activation of quiescent stem cells. Young and colleagues
      demonstrated that connective tissues throughout the body contain multiple
      populations of quiescent lineage-committed progenitor stem cells and lineage
      uncommitted pluripotent stem cells. Subsequent cloning and cell sorting studies
      identified quiescent lineage-uncommitted pluripotent mesenchymal stem cells,
      capable of forming any mesodermal cell type, and pluripotent epiblastic-like stem
      cells, capable of forming any somatic cell type. Based on their studies, they
      propose at least 11 categories of quiescent reserve stem cells resident within
      postnatal animals, including humans. These categories are pluripotent epiblastic
      like stem cells, pluripotent ectodermal stem cells, pluripotent epidermal stem
      cells, pluripotent neuronal stem cells, pluripotent neural crest stem cells,
      pluripotent mesenchymal (mesodermal) stem cells, pluripotent endodermal stem
      cells, multipotent progenitor stem cells, tripotent progenitor stem cells,
      bipotent progenitor stem cells, and unipotent progenitor stem cells. Thus,
      activation of quiescent reserve stem cells, i.e., lineage-committed progenitor
      stem cells and lineage-uncommitted pluripotent stem cells, resident within the
      connective tissues could provide for the continual maintenance and repair of the
      postnatal organism after birth.

PMID- 14594209
TI  - Genetic regulation of mouse stem cells: identification of two keratinocyte stem
      cell regulatory loci.
AB  - It is well documented that the bulge of hair follicle is a 'niche' for a
      significant population of mouse keratinocyte stem cells, and 95% of rodent
      clonogenic keratinocytes originate from the bulge region. The ability to form
      colonies in vitro is a well recognized test for keratinocyte stem cells. We
      analyzed the epidermis of seven mouse strains and their segregating crosses
      [(BALB/c x C57BL/6)F1; (BALB/c x CB6F1); (C57BL/ 6 x CB6F1); (CBF1 x CBF1)F2] for
      their clonogenic activity in vitro. We found that keratinocyte colony (KC) number
      is a new quantitative multigenic trait. The analysis of KC size in two parental
      strains (C57BL/6 and BALB/c), the F1 generation and the segregating crosses
      demonstrated that the size of KC is a quantitative complex trait also. We
      determined that mouse epidermis has at least two subpopulations of keratinocytes
      that gave small (< 2 mm2) and large (> 2 mm2) colonies. The differences in the
      number of small and large colonies between parental strains (C57BL/6, BALB/c)
      were significant (P < 0.01). A genome-wide scan of the intercross and the two
      backcrosses maps the number of small KC to the central region of mouse Chromosome
      9 (genomewide P value = 0.01). We define this locus as Ksc1. The proximal region
      of chromosome 4 is associated with the high number of large KC. We defined this
      locus as Ksc2. We found that Ksc1 and minor loci on chromosomes 6 and 7 map
      close, if not equal to, loci associated with mouse skin carcinogenesis. We
      conclude that mouse epidermis has at least two subpopulations of clonogenic
      keratinocyte stem cells that are regulated by different genes. We suggest that
      keratinocyte stem cells responsible for small colonies may play a major role in
      the regulation of resistance or sensitivity to skin carcinogenesis. Investigation
      of the genes regulating the stem cell number should provide new insight into the
      mechanisms of skin carcinogenesis, and should help to develop new approaches for
      therapies not only against active proliferating tumor cells but also quiescent
      tumor stem cells.

PMID- 14594210
TI  - Myocardial tissue engineering and regeneration as a therapeutic alternative to
      transplantation.
AB  - Ischemic cardiomyopathy leading to congestive heart failure remains the leading
      source of morbidity and mortality in Western society and medical management of
      this condition offers only palliative treatment. While allogeneic heart
      transplantation can both extend and improve the quality of life for patients with
      end-stage heart failure, this therapeutic option is limited by donor organ
      shortage. Even after successful transplantation, chronic cardiac rejection in the
      form of cardiac allograft vasculopathy can severely limit the lifespan of the
      transplanted organ. Current experimental efforts focus on cellular
      cardiomyoplasty, myocardial tissue engineering, and myocardial regeneration as
      alternative approaches to whole organ transplantation. Such strategies may offer
      novel forms of therapy to patients with end-stage heart failure within the near
      future.

PMID- 14594211
TI  - Spallanzani's mouse: a model of restoration and regeneration.
AB  - The ability to regenerate is thought to be a lost phenotype in mammals, though
      there are certainly sporadic examples of mammalian regeneration. Our laboratory
      has identified a strain of mouse, the MRL mouse, which has a unique capacity to
      heal complex tissue in an epimorphic fashion, i.e., to restore a damaged limb or
      organ to its normal structure and function. Initial studies using through-and
      through ear punches showed rapid full closure of the ear holes with cartilage
      growth, new hair follicles, and normal tissue architecture reminiscent of
      regeneration seen in amphibians as opposed to the scarring usually seen in
      mammals. Since the ear hole closure phenotype is a quantitative trait, this has
      been used to show-through extensive breeding and backcrossing--that the trait is
      heritable. Such analysis reveals that there is a complex genetic basis for this
      trait with multiple loci. One of the major phenotypes of the MRL mouse is a
      potent remodeling response with the absence or a reduced level of scarring. MRL
      healing is associated with the upregulation of the metalloproteinases MMP-2 and
      MMP-9 and the downregulation of their inhibitors TIMP-2 and TIMP-3, both present
      in inflammatory cells such as neutrophils and macrophages. This model has more
      recently been extended to the heart. In this case, a cryoinjury to the right
      ventricle leads to near complete scarless healing in the MRL mouse whereas
      scarring is seen in the control mouse. In the MRL heart, bromodeoxyuridine uptake
      by cardiomyocytes filling the wound site can be seen 60 days after injury. This
      does not occur in the control mouse. Function in the MRL heart, as measured by
      echocardiography, returns to normal.

PMID- 14594212
TI  - Phosphoinositide involvement in phagocytosis and phagosome maturation.
AB  - Cells of the innate immune system engulf invading microorganisms into plasma
      membrane-derived vacuoles called phagosomes. Newly formed phagosomes gradually
      acquire microbicidal properties by a maturation process which involves sequential
      and coordinated rounds of fusion with endomembranes and concomitant fission. Some
      pathogens interfere with this maturation sequence and thereby evade killing by
      the immune cells, managing to survive intracellularly as parasites.
      Phosphoinositides seem to be intimately involved in the processes of phagosome
      formation and maturation, and initial observations suggest that the ability of
      some microorganisms to survive intracellularly is associated with alterations in
      phosphoinositide metabolism. This chapter presents a brief overview of
      phosphoinositides in cells of the immune system, their metabolism in the context
      of phagocytosis and phagosome maturation and their possible derangements during
      infectious pathogenosis.

PMID- 14594213
TI  - Regulation of endocytosis by phosphatidylinositol 4,5-bisphosphate and ENTH
      proteins.
AB  - Clathrin-mediated endocytosis starts by a recruitment of endocytic proteins to
      the plasma membrane to induce invagination of lipid bilayer and subsequent
      vesicule formation. The recruitment of these components requires PtdIns(4,5)P2, a
      phosphoinositide on the plasma membrane. Although it is well known that the
      synthesis as well as the disruption of this lipid is important, recent studies
      have revealed the indispensable roles of direct interaction between PtdIns(4,5)P2
      and the endocytic machinery. The ENTH domain is a newly found PtdIns(4,5)P2
      binding unit conserved among endocytic proteins like epsins, AP180, and the
      Hip1/Sla2 family. This review focuses on the essential roles of PtdIns(4,5)P2 and
      its specific binding partner, the ENTH domain, in clathrin-mediated endocytosis.

PMID- 14594214
TI  - Membrane targeting by pleckstrin homology domains.
AB  - Pleckstrin homology (PH) domains are small modular domains that occur once, or
      occasionally several times, in a large variety of signalling proteins. In a
      number of instances, PH domains act to target their host protein to the cytosolic
      face of cellular membranes through an ability to associate with
      phosphoinositides. In this review, we discuss recent advances in our
      understanding of PH domain function. In particular we describe the structural
      aspects of how PH domains have evolved to bind various phosphoinositides, how PH
      domains regulate phosphoinositide-mediated association to plasma and internals
      membranes, and finally raise the issue of PH domains in protein:protein
      interactions and the allosteric regulation of their host protein.

PMID- 14594215
TI  - Protein targeting to endosomes and phagosomes via FYVE and PX domains.
AB  - Phosphatidylinositol 3-phosphate (PI3P) is generated on early endosomal and
      phagosomal membranes by PI 3-kinases. This lipid serves important regulatory
      functions in phagocytosis, endocytic traffic, receptor signalling and microbial
      killing through the recruitment and activation of a number of effector proteins.
      Almost all of these effectors contain FYVE or PX domains, functional protein
      modules which are conserved from yeast to mammals. Structural information is
      available regarding the binding of FYVE and PX domains to PI3P. The two domains
      are highly different, but they have in common that clusters of basic residues
      mediate ligand binding through interactions with the phosphate groups of PI3P.
      Most proteins that contain FYVE or PX domains serve as regulators of endocytic
      membrane trafficking, whereas others function as regulators of phagosome
      maturation, signal transduction, microbial killing and other cellular activities
      of relevance for the immune system.

PMID- 14594216
TI  - Regulation of the actin cytoskeleton by PI(4,5)P2 and PI(3,4,5)P3.
AB  - The actin cytoskeleton is fundamental for various motile and morphogenetic
      processes in cells. The structure and dynamics of the actin cytoskeleton are
      regulated by a wide array of actin-binding proteins, whose activities are
      controlled by various signal transduction pathways. Recent studies have shown
      that certain membrane phospholipids, especially PI(4,5)P2 and PI(3,4,5)P3,
      regulate actin filament assembly in cells and in cell extracts. PI(4,5)P2 appears
      to be a general regulator of actin polymerization at the plasma membrane or at
      membrane microdomains, whereas PI(3,4,5)P3 promotes the assembly of specialized
      actin filament structures in response to some growth factors. Biochemical studies
      have demonstrated that the activities of many proteins promoting actin assembly
      are upregulated by PI(4,5)P2, whereas proteins that inhibit actin assembly or
      promote filament disassembly are down-regulated by PI(4,5)P2. PI(3,4,5)P3
      promotes its effects on the actin cytoskeleton mainly through activation of the
      Rho family of small GTPases. In addition to their effects on actin dynamics, both
      PI(4,5)P2 and PI(3,4,5)P3 promote the formation of specific actin filament
      structures through activation/inactivation of actin filament cross-linking
      proteins and proteins that mediate cytoskeleton-plasma membrane interactions.

PMID- 14594217
TI  - Roles of PI3K in neutrophil function.
AB  - Neutrophils are terminally differentiated cells that play a vital role in host
      defense. It has recently become evident that phospholipid regulation plays an
      import role in many neutrophil functions. We review the regulation of neutrophil
      functions such as chemotaxis, superoxide production, and phagocytosis by
      phosphatidylinositol-3,4,5-trisphosphate (PIP3), which is generated in
      neutrophils by PI3K(gamma). Several lines of evidence are presented demonstrating
      the importance of this kinase in regulating chemotaxis, in particular the
      directionality of chemotactic migration. Evidence suggesting that this kinase is
      important for phagocytosis, especially during engulfment and the internalization
      of large particles, is also reviewed. Finally, it is suggested that PI3K is
      important for superoxide production and neutrophil priming. The common link
      between these seemingly diverse functions is that PI3K(gamma), via its
      phospholipid products, appears to be providing spatial-temporal cues for the
      binding of actin-organizing proteins.

PMID- 14594218
TI  - Nuclear phosphoinositides and their functions.
AB  - Phosphoinositides are minor components of biological membranes, which have
      emerged as essential regulators of a variety of cellular processes, both on the
      plasma membrane and on several intracellular organelles. The versatility of these
      lipids stems from their ability to function either as substrates for the
      generation of second messengers, as membrane-anchoring sites for cytosolic
      proteins or as regulators of the actin cytoskeleton. Despite a vast literature
      demonstrating the presence of phosphoinositides in the nucleus, only recently has
      the function(s) of the nuclear pool of these lipids and their soluble analogues,
      inositol polyphosphates, started to emerge. These compounds have been shown to
      serve as essential co-factors for several nuclear processes, including DNA
      repair, transcription regulation and RNA dynamics. In this light,
      phosphoinositides and inositol polyphosphates might represent high turnover
      activity switches for nuclear complexes responsible for these processes. The
      regulation of these large machineries would be linked to the phosphorylation
      state of the inositol ring and limited temporally and spatially based on the
      synthesis and degradation of these molecules.

PMID- 14594219
TI  - Invited review: bovine studies on optimal lengths of dry periods.
AB  - Milk production per cow has increased as a result of progressive changes in the
      genetics and management of the dairy animal population. A management constant
      during many decades of progress has been the widely adopted dry period length of
      51 to 60 d. The scientific basis for that industry standard was examined to
      assess its validity as the appropriate standard for the modern dairy industry. If
      subsequent milk yields can be sustained fully after dry periods that are shorter
      than the current standard, then considerable milk is being forfeited by retaining
      longer dry periods. Conversely, failure to allow any dry period will result in a
      significant decrease in subsequent milk synthesis and secretion. Most studies to
      determine the minimum length of dry period required have involved retrospective
      analyses of observational data. Only five experiments have been reported in which
      dairy cows were assigned, at random, to planned 30- and 60-d dry periods.
      Estimates of the change in subsequent milk production when days dry were
      decreased from 50 to 57 d to 30 to 34 d ranged from a 10% decrease to a 1%
      increase. However, lower yields after shorter dry periods may be partially offset
      by greater milk yields in the previous lactation if such cows are milked 3 to 4
      wk longer. Environmental factors that influence milk production as well as the
      biological processes that occur within the mammary gland during the nonlactating
      period must be considered when dry period lengths are compared. Importantly,
      additional animal trials that specifically assign cows randomly to the dry period
      lengths to be evaluated are needed to determine optimal dry period lengths for
      modern dairy cows in differing management scenarios.

PMID- 14594220
TI  - Proteolysis, volatile compounds, and sensory evaluation in Hispanico cheese
      manufactured with the addition of a thermophilic adjunct culture, nisin, and
      calcium alginate-nisin microparticles.
AB  - Nisin, free or incorporated in calcium alginate microparticles, was added to
      pasteurized milk (80% cows' and 20% ewes' milk) used for the manufacture of
      Hispanico cheese with a mesophilic starter and a thermophilic adjunct culture of
      high aminopeptidase activity. Addition of nisin incorporated in microparticles
      promoted early lysis of thermophilic adjunct culture bacteria. Extracellular
      aminopeptidase activity in 1-d-old cheese made with both thermophilic adjunct
      culture and nisin incorporated in microparticles was 1.8-fold higher than in
      cheese made with thermophilic adjunct culture and free nisin and 2.0-fold higher
      than in cheese made only with thermophilic adjunct culture without any addition
      of nisin. Addition of nisin, free or incorporated in microparticles, did not
      influence cheese proteolysis measured using hydrophilic or hydrophobic peptides,
      o-phthaldialdehyde ripening index, or free amino acids. Moreover, a total of 37
      volatile compounds were identified in the volatile fraction of Hispanico cheese,
      using a dynamic headspace technique with a purge and trap system followed by a
      gas chromatography mass spectrometry analysis. The volatile compound profile was
      not influenced by nisin addition, either free or incorporated in microparticles,
      but addition of thermophilic adjunct culture enhanced the formation of 2
      butanone, diacetyl, 2,3-pentanedione and acetoin and improved the flavor quality
      (sensory panel) of cheese.

PMID- 14594221
TI  - Improvement of the resistance of Lactobacillus delbrueckii ssp. bulgaricus to
      freezing by natural selection.
AB  - Lactic acid bacteria are often produced as frozen or freeze-dried cultures that
      can be used for the direct inoculation of milk in cheese and fermented milk
      production processes. The objective of this study was to investigate whether the
      resistance of Lactobacillus delbrueckii ssp. bulgaricus to freezing could be
      improved by natural selection. Three parallel cultures of strain CFL1 were
      propagated for 30 cycles in which each cycle involved three serial transfers
      through milk, one freezing step, and one thawing step. The concentration in
      viable cells after thawing as well as the acidifying activity of the thawed
      cultures increased dramatically throughout the experiment. This may be explained
      by the random appearance of better-adapted mutants that can outcompete the other
      genotypes. However, after 30 cycles of subcultivation, freezing, and thawing, all
      the cultures contained subpopulations having different survival rates to
      freezing. Our results show that serial transfer culture experiments may be used
      to improve technological properties of lactic acid bacteria. Furthermore,
      investigation of the mutations that are responsible for an increased
      cryotolerance may help to define new targets for improving the resistance of
      lactic acid bacteria to several stresses.

PMID- 14594222
TI  - Relationships among rheological and sensorial properties of young cheeses.
AB  - This study investigated the sensory and rheological properties of young cheeses
      in order to better understand perceived cheese texture. Mozzarella and Monterey
      Jacks were tested at 4, 10, 17, and 38 d of age; process cheese was tested at 4
      d. Rheological methods were used to determine the linear and nonlinear
      viscoelastic and fracture properties. A trained sensory panel developed a
      descriptive language and reference scales to evaluate cheese texture. All methods
      differentiated the cheeses by variety. Principal component analysis of sensory
      texture revealed that three principal components explained 96.1% of the total
      variation in the cheeses. The perception of firmness decreased as the cheeses
      aged, whereas the perception of springiness increased. Principal component
      analysis of the rheological parameters (three principal components: 87.9% of the
      variance) showed that the cheeses' solid-like response (storage modulus and
      fracture modulus) decreased during aging, while phase angle, maximum compliance,
      and retardation time increased. Analysis of the instrumental and sensory
      parameters (three principal components: 82.1% of the variance) revealed groupings
      of parameters according to cheese rigidity, resiliency, and chewdown texture.
      Rheological properties were highly associated with rigidity and resiliency, but
      less so with chewdown texture.

PMID- 14594223
TI  - Streptococcus thermophilus 580 produces a bacteriocin potentially suitable for
      inhibition of Clostridium tyrobutyricum in hard cheese.
AB  - A strain of Streptococcus thermophilus that inhibits Clostridium tyrobutyricum
      has been isolated from raw milk. The active compound produced disappears after a
      treatment with protease. However, unlike most bacteriocins, it is not
      thermoresistant, and the activity is completely lost after 1 h at 60 degrees C.
      Its inhibitory spectrum is limited to other thermophilic streptococci,
      Brochothrix, and sporulated gram-positive rods. So this bacteriocin could be
      different from those already described. This bacteriocin-producing strain could
      be used in thermophilic starter for hard cheese making because the bacteriocin is
      not active against thermophilic lactobacilli. It is produced in M17 medium during
      the decreasing temperature phase of the hard cheese-making process temperature
      cycle and is also produced in milk. Moreover, when Streptococcus thermophilus was
      cocultured with a Lactobacillus delbrueckii subsp. lactis starter strain, it
      seems to enhance the bacteriocin production. However the level of activity always
      decreases drastically during the stationary phase. But inhibition of Clostridium
      tyrobutyricum spores can be obtained in small-scale curds.

PMID- 14594224
TI  - Inactivation of spores of Bacillus cereus in cheese by high hydrostatic pressure
      with the addition of nisin or lysozyme.
AB  - The objective of this work was to study high hydrostatic pressure (HHP)
      inactivation of spores of Bacillus cereus ATCC 9139 inoculated in model cheeses
      made of raw milk, together with the effects of the addition of nisin or lysozyme.
      The concentration of spores in model cheeses was approximately 6-log10 cfu/g of
      cheese. Cheeses were vacuum packed and stored at 8 degrees C. All samples except
      controls were submitted to a germination cycle of 60 MPa at 30 degrees C for 210
      min, to a vegetative cells destruction cycle of 300 or 400 MPa at 30 degrees C
      for 15 min, or to both treatments. Bacillus cereus counts were measured 24 h and
      15 d after HHP treatment. The combination of both cycles improved the efficiency
      of the whole treatment. When the second pressure-cycle was of 400 MPa, the
      highest inactivation (2.4 +/- 0.1 log10 cfu/g) was obtained with the presence of
      nisin (1.56 mg/L of milk), whereas lysozyme (22.4 mg/L of milk) did not increase
      sensitivity of the spores to HHP. For nisin (0.05 and 1.56 mg/L of milk), no
      significant differences were found between counts at 24 h and 15 d after
      treatment. Considering that mesophilic spore counts usually range from 2.6 to 3.0
      log10 cfu/ml in raw milk, HHP at mild temperatures with the addition of nisin may
      be useful for improving safety and preservation of soft curd cheeses made from
      raw milk.

PMID- 14594226
TI  - Use of multi-angle laser light scattering and size-exclusion chromatography to
      characterize the molecular weight and types of aggregates present in commercial
      whey protein products.
AB  - In this study, a range of commercial whey protein products were characterized by
      the use of size-exclusion chromatography coupled with a multi-angle laser light
      scattering (MALLS) detector. The MALLS system detected some very large-sized
      material that eluted close to void volume in all samples; this material was
      hardly detected by concentration detector. It was demonstrated by chitosan
      treatment that this peak was very small lipid globules or phospholipids, which
      gave the residual "cloudy" appearance in upper layers after ultracentrifugation
      of whey products. Composition, molecular weight, and the photo diode array (PDA)
      spectrum (200 to 400 nm) of the major protein peaks, including: beta
      lactoglobulin (BLG), alpha-lactalbumin (ALA), bovine serum albumin (BSA),
      immunoglobulin G (IgG) and some minor components were analyzed. The molecular
      weight of BLG, ALA, BSA, and IgG peaks in whey protein isolates (WPI) were 2.3 to
      3.7 x 10(4), 1.4 to 1.6 x 10(4), 4.8 to 6.7 x 10(4), and 1.2 to 2.5 x 10(5) Da,
      respectively. Compared with WPI, WPC has similar major proteins, but more large
      sized residual lipid material and different minor constituents such as lactose
      and nonprotein nitrogen, depending on various commercial samples and protein
      content. An improved TCA-precipitation method was applied to quantify
      glycomacropeptide (GMP) in whey proteins, which demonstrated that there was a
      very low concentration of GMP in WPI manufactured using an ion-exchange process.
      The molecular weight of GMP was found to be approximately 8600 Da. Size-exclusion
      chromatography MALLS was demonstrated to be a powerful technique for detailed
      analysis of the molecular weight of various proteins, aggregates and minor
      components, such as GMP, in whey protein products.

PMID- 14594225
TI  - Hard ewe's milk cheese manufactured from milk of three different groups of
      somatic cell counts.
AB  - As ovine milk production increases in the United States, somatic cell count (SCC)
      is increasingly used in routine ovine milk testing procedures as an indicator of
      flock health. Ovine milk was collected from 72 East Friesian-crossbred ewes that
      were machine milked twice daily. The milk was segregated and categorized into
      three different SCC groups: < 100,000 (group I); 100,000 to 1,000,000 (group II);
      and > 1,000,000 cells/ ml (group III). Milk was stored frozen at -19 degrees C
      for 4 mo. Milk was then thawed at 7 degrees C over a 3-d period before
      pasteurization and cheese making. Casein (CN) content and CN-to-true protein
      ratio decreased with increasing SCC group 3.99, 3.97, to 3.72% CN, and 81.43,
      79.72, and 79.32% CN to true protein ratio, respectively. Milk fat varied from
      5.49, 5.67, and 4.86% in groups I, II, and III, respectively. Hard ewe's milk
      cheese was made from each of the three different SCC groups using a Manchego
      cheese manufacturing protocol. As the level of SCC increased, the time required
      for visual flocculation increased, and it took longer to reach the desired
      firmness for cutting the coagulum. The fat and moisture contents were lower in
      the highest SCC cheeses. After 3 mo, total free fatty acids (FFA) contents were
      significantly higher in the highest SCC cheeses. Butyric and caprylic acids
      levels were significantly higher in group III cheeses at all stages of ripening.
      Cheese graders noted rancid or lipase flavor in the highest SCC level cheeses at
      each of the sampling points, and they also deducted points for more body and
      textural defects in these cheeses at 6 and 9 mo.

PMID- 14594227
TI  - Quantification of short-chain free fatty acids in "Terrincho" ewe cheese:
      intravarietal comparison.
AB  - Headspace solid-phase microextraction coupled with gas chromatography-mass
      spectrometry was employed for the quantification of volatile free fatty acids
      (FFA) in "Terrincho" ewe cheese. Solid-phase microextraction quantitative
      analysis was feasible under equilibrium situations as long as the conditions of
      agitation and the adsorption time were held constant. An excellent linear
      relationship between the amount of the adsorbed analyte and its initial
      concentration in the sample matrix was obtained when an adequate amount of sample
      was chosen. Thus, quantification was possible if biases due to competition or
      linear range excesses were controlled. Solid-phase microextraction sampling was
      carried out at 65 degrees C, and a fiber coated with an 85-micro/m polyacrylate
      film was chosen. After equilibration at 65 degrees C for 40 min, the fiber was
      exposed to the headspace above the sample for 20 min and then inserted into the
      gas chromatograph. The evolution of the volatile FFA during Terrincho ewe cheese
      ripening was analyzed for a 60-d period. An overall increase in FFA contents was
      verified up to 30 d of ripening. Between 30 and 45 d most FFA did not suffer
      significant changes. All FFA increased significantly by the 60-d ripening period.
      The excessive lipolysis observed at 60 d of ripening may result in the presence
      of off-flavors. Principal component analysis performed for intravarietal
      comparison of volatile FFA composition of 19 Terrincho cheeses, analyzed at 30
      ripening days, enabled discrimination between cheeses produced at five different
      dairy plants.

PMID- 14594228
TI  - Short communication: estimate of non electrostatic interaction free energy
      parameters for milk fat globules.
AB  - The surface free energy components for bovine milk fat globules (MFG) were
      calculated by solving a modified Young-Good-Fowkes-Girafalco equation with
      experimentally obtained contact angles for liquids of known surface tension
      components. The surface free energy of MFG was dominated by the electron donor
      term (gamma-), which formed the basis of a significant repulsive acid-base
      interaction free energy term at the minimum equilibrium distance. Consideration
      of the decay of the acid-base and Lifshitz-van der Waals energy term over
      distance within the context of an "extended DLVO" model shows that physical
      contact of MFG in the absence of electrostatic repulsion (at their isoelectric
      point) is prohibited by the acid-base term but that "pseudo-flocculation" might
      occur at 4- to 5-nm separation in an energy minimum that was approximately 15 kT
      for MFG of diameter = 1.0 microm.

PMID- 14594229
TI  - Effect of sodium citrate on structure-function relationships of Cheddar cheese.
AB  - The objective of this study was to determine the effect of sodium citrate on the
      structure and functionality of Cheddar cheese. The hypothesis was that citrate
      (sodium citrate) injection would affect cheese properties mainly through its
      effect on bound calcium (calculated as the difference between total calcium and
      the water-soluble calcium content of a cheese extract). A 9-kg block of Cheddar
      cheese was made, vacuum-packaged, and then stored for 2 wk at 4 degrees C. After
      storage, the cheese was cut into 0.5- to 0.6-kg blocks that were vacuum-packaged
      and stored for 1 wk at 4 degrees C prior to injection. Cheese blocks were then
      high-pressure injected with a buffer solution (pH 5.27) containing 40% (wt/ wt)
      citric acid trisodium dihydrate and 6.25% (wt/wt) anhydrous citric acid, from
      zero (control) to five times (successive injections performed 24 h apart).
      Increased citric acid content of cheese from 0.22 (uninjected) to 1.39% (after
      five injections) caused phosphate solubilization. Thus, the calculated bound
      phosphate content of cheese decreased from 0.54 to 0.45 mmol/g of protein.
      However, unexpectedly, the soluble calcium content decreased from 0.34 (control)
      to 0.28 mmol/g of protein (after five injections), whereas the bound calcium
      content remained unchanged (0.42 mmol/g of protein). The decrease in soluble
      calcium probably resulted from the formation and concentration of crystals in the
      cheese surface, which was not included in samples for analysis, and from the
      expulsion of serum from within the cheese. Higher concentration of solutes in the
      water phase of cheese would increase the volume of serum, but the cheese had
      limited holding capacity and serum was expelled. Citrate injection increased the
      sodium content of cheese from 0.63 to 0.93%, but it had no effect on cheese pH
      (5.2). After five injections, the protein matrix expanded, occupying an increased
      area of cheese matrix (83 vs. 78%). Even though citrate injection had no effect
      on bound calcium, and thus the rate and extent of cheese flow were unaffected,
      increased phosphate solubilization, and possibly decreased ionic calcium content,
      resulted in expansion of the protein matrix and increased cheese hardness.

PMID- 14594230
TI  - Texture of butter from cows with different milk fatty acid compositions.
AB  - Milk fatty acid composition and textural properties of butter are known to be
      affected by the cows' diets. We examined the phenotypic variation in milk fatty
      acid composition among cows fed the same diet to see if the variation was
      sufficient to produce butter with different textural properties. Ten cows were
      selected that tested higher (n = 5) or lower (n = 5) in their proportion of milk
      unsaturated fatty acids. Milk samples were collected a week after testing, and
      butter was prepared from the individual samples. Milk and butter samples were
      again analyzed for fatty acid composition. Butter at 5 degrees C was evaluated by
      a sensory panel for spreadability and by a texture analyzer at both 5 and 23
      degrees C for hardness and adhesiveness. Milk and butter samples from cows with a
      more unsaturated milk fatty acid composition had a lower atherogenic index, and
      the butter samples were more spreadable, softer, and less adhesive. Thus,
      phenotypic variation in milk fatty acid composition among cows fed the same diet
      is sufficient to produce butter with different textural properties.

PMID- 14594231
TI  - Increased levels of LPS-binding protein in bovine blood and milk following
      bacterial lipopolysaccharide challenge.
AB  - Several species of gram-negative bacteria, including Escherichia coli, Klebsiella
      pneumoniae, and various species of Enterobacter, are common mastitis pathogens.
      All of these bacteria are characterized by the presence of endotoxin or
      lipopolysaccharide (LPS) in their outer membrane. The bovine mammary gland is
      highly sensitive to LPS, and LPS has been implicated, in part, in the
      pathogenesis of gram-negative mastitis. Recognition of LPS is a key event in the
      innate immune response to gram-negative infection and is mediated by the
      accessory molecules CD14 and LPS-binding protein (LBP). The objective of the
      current study was to determine whether LBP levels increased in the blood and
      mammary gland following LPS challenge. The left and right quarters of five
      midlactating Holstein cows were challenged with either saline or LPS (100
      microg), respectively, and milk and blood samples collected. Basal levels of
      plasma and milk LBP were 38 and 6 microg/ml, respectively. Plasma LBP levels
      increased as early as 8 h post-LPS challenge and reached maximal levels of 138
      microg/ ml by 24 h. Analysis of whey samples derived from LPS-treated quarters
      revealed an increase in milk LBP by 12 h. Similar to plasma, maximal levels of
      milk LBP (34 microg/ml) were detected 24 h following the initial LPS challenge.
      Increments in milk LBP levels paralleled a rise in soluble CD14 (sCD14) levels
      and initial rises in the levels of these proteins were temporally coincident with
      maximal neutrophil recruitment to the inflamed gland. Because LBP and sCD14 are
      known to enhance LPS-induced host cell activation and to facilitate
      detoxification of LPS, these data are consistent with a role for these molecules
      in mediating mammary gland responses to LPS.

PMID- 14594232
TI  - Potential treatment of fatty liver with 14-day subcutaneous injections of
      glucagon.
AB  - Fatty liver is a major metabolic disease of dairy cows in early lactation that
      can be treated with 14-d continuous, intravenous infusions of 10 mg/d of
      glucagon. The objective was to test whether similar effects can be obtained with
      14-d subcutaneous 7.5- or 15-mg daily dosages of glucagon beginning at d 8
      postpartum. Multiparous Holstein cows (n = 32) were grouped on the basis of their
      liver triacylglycerol concentration at d 8 postpartum into "normal" (n = 8;
      triacylglycerol < 1% liver wet wt) and "susceptible" (n = 24; triacylglycerol >
      1% liver wet wt) cows. Susceptible cows were assigned randomly to three groups
      and beginning at d 8 postpartum received 0, 2.5, or 5 mg of glucagon in 60 ml of
      saline by subcutaneous injections every 8 h for 14 d. Beginning at d 8
      postpartum, normal cows received 60 ml of saline by subcutaneous injections every
      8 h for 14 d. Both dosages of glucagon increased concentrations of plasma glucose
      and insulin and decreased concentrations of plasma nonesterfied fatty acids.
      Glucagon injections of 15 mg/d decreased concentrations of liver triacylglycerol
      in cows older than 3.5 yr, but not in younger multiparous cows. Our results
      document that subcutaneous injections of glucagon have the potential to decrease
      the degree of fatty liver in older dairy cows in early lactation.

PMID- 14594233
TI  - Modeling the effect of energy status on mammary gland growth and lactation.
AB  - The impact of nutrition on lactation can be separated into acute effects,
      affecting day-to-day yield, and chronic effects, which govern the persistency of
      lactation and rate of decline of the lactation curve. A mathematical model of the
      mammary gland was constructed to investigate both acute and chronic effects.
      Mammary growth is expressed in terms of the dynamics of populations of active
      (secreting) and quiescent (engorged) alveoli. The secretion rate of active
      alveoli is expressed in terms of the energy status of the dam. The model was
      fitted to data from a 2 x 2 factorial trial in which lactation curves were
      measured for heifers of two different genotypes (North American and New Zealand
      Holstein-Friesians) fed two different diets [grass and total mixed rations
      (TMR)]. Total formation of alveoli during pregnancy and lactation was
      statistically the same across all groups despite differences between diets, in
      the rate of formation of alveoli at parturition. The senescence rate of alveoli
      was significantly higher for heifers fed grass compared with heifers fed TMR,
      which corresponds to better persistency for heifers fed TMR. Heifers fed TMR had
      a higher rate of reactivation of quiescent alveoli than heifers fed grass, which
      also contributes to increased persistence for heifers fed TMR. There was a
      genotype x diet interaction in the rate of quiescence of active alveoli: the
      North American-Grass group had a higher rate of quiescence than the other three
      groups, perhaps reflecting differences in selection pressures between the New
      Zealand and North American genotypes.

PMID- 14594234
TI  - Antimicrobial drug susceptibility of Staphylococcus aureus strains isolated from
      bovine and ovine mammary glands.
AB  - The activity of selected antimicrobial agents against Staphylococcus aureus was
      determined with the agar disk diffusion test to determine the diameter of the
      zone of inhibition and the E-test for determination of the minimal inhibitory
      concentration (MIC). The 92 S. aureus strains used in this study were isolated
      from bovine (n = 76) and ovine (n = 16) intramammary infections. Four
      antibiotics, which are frequently used in mastitis therapy were chosen:
      penicillin-G, ampicillin, kanamycin, and cephalexine. The fifth compound
      (oxacillin) was used to detect methicillin-resistant S. aureus, but no such
      strains could be found. According to the evaluation criteria, 65.2 (penicillin)
      to 93.5% (kanamycin, cephalexine) S. aureus strains were susceptible to the
      antibiotics tested. Ovine S. aureus strains reveal a lower resistance rate than
      bovine isolates. Comparison of the results of the two methods of susceptibility
      testing shows, with exception of penicillin and ampicillin, satisfactory
      agreement. Analyzing the results of the MIC endpoints and the zone diameter
      values, very major errors, according to the error rate bounded method of Metzler
      and DeHaan, occurred at an error rate of 3.3% for penicillin and 3.8% for
      ampicillin.

PMID- 14594235
TI  - Hot topic: an association between a leptin single nucleotide polymorphism and
      milk and protein yield.
AB  - Allelic variation (C to T transition that results in an Arg25Cys) in the leptin
      gene has been associated with increased fat deposition in beef cattle. We report
      that this same genetic variant is also present in dairy breeds. Body fat reserves
      play an important role in sustaining high milk production in early lactation,
      when energy intake is limited. To test for an association between the leptin
      single nucleotide polymorphism and milk productivity, we genotyped 416 Holstein
      cows and compared lactation performance data using a mixed model. Animals
      homozygous for the T allele produced more milk (1.5 kg/d vs. CC animals) and had
      higher somatic cell count linear scores, without significantly affecting milk fat
      or protein percent over the entire lactation. The increase in milk yield is most
      prominent in the first 100 d of lactation (2.44 kg/d), declining to 1.74 kg/d
      between 101 and 200 d in lactation. The milk yield advantage, observed in cows
      homozygous for the T allele, could represent a major economic advantage to dairy
      producers.

PMID- 14594236
TI  - Laterality in bovine behavior in an extensive partially suckled herd and an
      intensive dairy herd.
AB  - Cattle exhibit behavioral laterality, but the consistency and correlation between
      behaviors are unknown. Behavioral laterality was recorded in two herds of
      contrasting management intensity. The first was a small, extensively managed herd
      in Brazil, with cows and calves on rangeland, except when removed for handmilking
      in stalls. The second was a large, intensive British herd, with cows fed mostly
      indoors and calves removed for individual rearing soon after birth. In herd 1,
      the side of the body on which the following behaviors were performed was
      recorded: rumination (rumination), tail waving (tail), tongue protrusion during
      the initiation of a feeding bout (feeding), hind leg placement when lying
      (lying), and front leg initiating walking (walking). The distribution of left and
      right side dominance was normal for all behaviors, with positive correlations
      between walking and rumination, tail, and feeding, and between lying and
      rumination. In herd 2, rumination, feeding, and lying behaviors were similarly
      recorded, as well as parlor side-preference (parlor) and the side of a track
      chosen when returning to pasture (track). For all behaviors except track, the
      extent of left- and right-side dominance was not normally distributed, and more
      cows than expected showed strong laterality on the right or the left side. Parlor
      and track lateralities were correlated, indicating that cows that entered one
      side of the parlor also tended to choose the same side of the track. Strong
      laterality in the intensively managed herd therefore contrasted with that
      observed in the extensively managed herd and the reasons for such differences in
      laterality are uncertain.

PMID- 14594237
TI  - Effect of mastitis treatment and somatic cell counts on milk yield in Danish
      organic dairy cows.
AB  - Production and disease data from 17,488 lactations in 48 Danish organic dairy
      herds from 1997 to 2001 were analyzed to obtain estimates on the effect of
      somatic cell counts (SCC) and mastitis treatment on milk production. A multilevel
      three-parameter piecewise random coefficients linear model with energy-corrected
      milk (ECM) as dependent variable and herd, lactation, and test days as levels,
      was used to model the lactation curve. Covariates related to production, SCC,
      veterinary treatments, and reproductive performance in the previous lactation as
      well as information on other diseases in the current lactation were included to
      describe the production capacity of the individual cow. The average daily milk
      production at herd level was 20.8, 24.2, and 25.8 kg of ECM/d in first, second,
      and third or later lactation. The estimates for production losses were on average
      0.2, 0.3, and 0.4 kg of ECM/d in first, second, and third or later lactation with
      each twofold increase in SCC between 100,000 and 1,500,000 cells/ml. The effect
      varied with the stage of lactation and was nonsignificant around 60 d postpartum
      and highest at the end of the lactation. The production losses in cows treated
      for mastitis varied with parity and stage of lactation and were modified by the
      SCC after treatment. For a cow in third lactation with a SCC below 100,000 cells/
      ml before treatment at days in milk = 15, the predicted loss was 435 kg of ECM,
      including a loss of 135 kg of ECM because of higher SCC compared with the level
      before treatment. Most of the variation in production related to SCC and mastitis
      was at the lactation level, and no significant differences were found between
      herds grouped according to milk production level, SCC, or prevalence of mastitis
      treatment.

PMID- 14594238
TI  - Follicular size and response to Ovsynch versus detection of estrus in anovular
      and ovular lactating dairy cows.
AB  - In a commercial dairy herd, 316 lactating Holsteins were studied to determine the
      percentage of anovular cows, to examine follicular sizes in anovular cows, and to
      compare synchronized ovulation (Ovsynch) versus detection of estrus on fertility
      of ovular and anovular cows. Ultrasonography examinations at 47 to 53 d and at 54
      to 60 d postpartum were used to measure follicles and to classify cows as ovular
      or anovular. Anovular cows were identified as those with no detectable luteal
      tissue by ultrasonography and by low progesterone in blood samples collected
      weekly. Anovular cows included 28% of 122 primiparous cows and 15% of 194
      multiparous cows. Of 64 anovular cows, 20% had follicles > or = 25 mm that might
      be considered cystic (4% of total cows), 58% had 15- to 24-mm follicles, and 22%
      had 9- to 14-mm follicles. Cows identified as ovular and anovular were randomly
      assigned within cyclic status to one of two artificial insemination (AI)
      strategies: 1) AI after detected estrus during 21 d, or 2) timed AI after a 10-d
      Ovsynch protocol. Weekly ultrasonography continued for 21 d to detect ovulations.
      For the Ovsynch sub-groups, 97% of ovular and 94% of anovular cows ovulated after
      the second GnRH injection. Within 21 d, spontaneous ovulations for the detection
      of estrus sub-groups were 42% of anovular cows vs. 89% of ovular cows. Conception
      rates were greater for ovular cows regardless of treatment, but conception rates
      between respective Ovsynch and estrus detection groups for ovular (32%, 35%) or
      anovular (9%, 11%) cows were similar. Although 20% of lactating cows were not
      cyclic by about 60 d postpartum, nearly all ovulated following Ovsynch. However,
      anovular cows had lower conception than ovular cows whether inseminated after
      detected estrous or after Ovsynch.

PMID- 14594239
TI  - Responses of Holstein cows to a low dose of somatotropin (bST) prepartum and
      postpartum.
AB  - Objectives were to evaluate the effects of a low dose of bovine somatotropin
      (bST) injected prepartum and postpartum on body condition score (BCS), body
      weight (BW), and milk yield (MY) in cows as well as somatotropin insulin, insulin
      like growth factor-I (IGF-I), glucose, and nonesterified fatty acids (NEFA) in
      plasma. Holstein cows nearing second or later parities were assigned randomly to
      control (CON = 98) or bST-treated (TRT = 95) groups. Biweekly injections of bST
      began 21 +/- 3 d before expected calving and continued through 42 d postpartum
      (CON vs. TRT; 0 vs. 10.2 mg of bST/ d). From 42 to 100 d postpartum, no cows
      received bST. During yr 1, somatotropin, IGF-I, insulin, NEFA, and glucose were
      measured in plasma samples from 82 cows. During yr 2, effects of bST on BCS and
      BW of 111 cows were evaluated, but no blood samples were collected. Milk yields
      through 100 d of all 193 cows were analyzed. Prepartum treatment with bST
      resulted in greater prepartum plasma concentrations of somatotropin, insulin, and
      numerically greater NEFA but did not affect glucose or IGF-I. Postpartum bST
      increased mean plasma concentrations of somatotropin and NEFA, but not INS, IGF
      I, or glucose. Mean BCS of cows did not differ prepartum, around parturition, or
      postpartum. Although mean BW did not differ prepartum or around calving, cows
      receiving bST maintained greater BW postpartum. Cows receiving bST tended to have
      higher MY (6.6%) in the first 60 d of lactation, but differences did not persist
      through 100 d, including approximately 40 d when no cows received bST. Number of
      cows that were culled due to health (CON = 3 vs. TRT = 2) or died (CON = 3 vs.
      TRT = 1) were not affected by treatment. Low doses of bST in the transition
      period resulted in higher postpartum BW, quicker recovery of body condition
      during lactation, and significantly more milk during treatment.

PMID- 14594240
TI  - Nutritional and developmental regulation of plasma leptin in dairy cattle.
AB  - Leptin is thought to play a critical role in regulating energy metabolism
      throughout mammalian life. In growing dairy cattle, plasma leptin has been
      proposed as a partial mediator of the effects of nutrition on reproductive and
      mammary development. However, the developmental stage at which the plane of
      nutrition increases plasma leptin has not been well defined. Further, it is
      unknown whether the onset of puberty is affected by plasma leptin concentration
      in dairy cattle. To investigate these questions, two studies were performed. In
      the first study, neonatal calves were fed a milk replacer at levels supporting an
      average daily gain of 570 g/d (L) or 1210 g/d (H). Weekly blood samples were
      obtained until slaughter at 105 kg of body weight. Plasma leptin and adiposity
      remained constant in the L calves, but started to increase by the third week of
      age in the H calves. In the second study, 3- to 5-mo-old heifers were fed a total
      mixed ration supplemented with either calcium salts of palm fat or conjugated
      linoleic acids at levels sustaining an average daily gain of approximately 1.0
      kg/d. Blood samples were obtained until the third postpubertal luteal phase. The
      fat source had no effects on growth parameters, body composition, age at puberty,
      or plasma leptin. Therefore, plasma leptin was reanalyzed as a function of age
      from start of treatment until slaughter. The plasma concentration of leptin
      remained nearly constant at 2.3 ng/ml until 1 yr of age, when a rise in plasma
      leptin became obvious. Puberty occurred with equal frequency either around 1 yr
      of age when plasma leptin was nearly constant or later when leptin was rising
      rapidly. We conclude that plasma leptin is regulated by nutrition in early
      postnatal life, but that a sudden increase in plasma leptin is not required for
      the onset of puberty in dairy cattle.

PMID- 14594241
TI  - Short communication: presynchronization using a single injection of PGF2alpha
      before synchronized ovulation and first timed artificial insemination in dairy
      cows.
AB  - Conception to synchronized ovulation (Ovsynch) using injections of GnRH and
      PGF2alpha and timed artificial insemination has been shown to be maximized when
      the program is initiated 5 to 12 d after estrus. The objective of this double
      blinded field trial was to assess the effect of one injection of PGF2alpha, 10 d
      before the Ovsynch program, on the probability of pregnancy at first insemination
      in lactating dairy cows. The hypothesis was that cows that underwent luteolysis
      in response to PGF2alpha would be between 5 and 8 d postestrus at the start of
      Ovsynch. In five commercial dairy herds in Ontario, Canada, at 52 +/- 12 d in
      milk, 506 cows were assigned at random to receive either one i.m. injection of
      500 microg of cloprostenol or saline. Ten days later, all cows received 100
      microg of GnRH i.m., followed in 7 d by 500 microg of cloprostenol i.m. and 100
      microg of GnRH i.m. 48 h later. All cows were artificially inseminated 0 to 20 h
      after the second injection of GnRH, without regard to detection of estrus.
      Pregnancy was diagnosed by transrectal palpation at least 35 d after
      insemination. The probability of pregnancy after first insemination was modeled
      with logistic regression, accounting for the correlation of cows with herd and
      the effect of season of calving. There was no difference in pregnancy risk
      between cows that received PGF2alpha presynchronization and controls (37.3 and
      36.6%, respectively; odds ratio = 1.03, 95% confidence interval, 0.88 to 1.20).
      Parity and days in milk at insemination were not significant covariates.

PMID- 14594242
TI  - Production responses of dairy cows to dietary supplementation with conjugated
      linoleic acid (CLA) during the transition period and early lactation.
AB  - Holstein cows (n = 30) entering second or greater lactation were fed fat
      supplements (90 g/d of fatty acids) consisting of Ca salts of either palm fatty
      acid distillate (control) or a mixture of palm fatty acid distillate and mixed
      isomers of conjugated linoleic acid (CLA, 30.4 g/ d) from 2 wk prepartum through
      20 wk postpartum to determine whether CLA would inhibit milk fat synthesis during
      early lactation and, in turn, affect energy metabolism of dairy cows during the
      transition period and early lactation. Feeding CLA did not affect DMI or plasma
      concentrations of glucose, nonesterfied fatty acids, or beta-hydroxbutyrate
      during the prepartum period and did not affect postpartum DMI. Feeding CLA
      reduced milk fat content by 12.5% during early lactation; however, cows fed CLA
      tended to produce approximately 3 kg/d more milk during the first 20 wk of
      lactation. Feeding CLA tended to decrease the contribution of short- and medium
      chain (C < or = 16) fatty acids to milk fat. Changes in milk yield, milk fat
      content, and milk fatty acid composition were not apparent until after the second
      week of lactation. Yield of 3.5% fat-corrected milk, milk protein content, milk
      protein composition, and calculated energy balance were not affected by
      treatment. Postpartum concentrations of glucose, nonesterfied fatty acids, and
      beta-hydroxbutyrate in plasma and hepatic content of glycogen and triglycerides
      were similar between treatments. These data imply that with CLA treatment in
      early lactation, dairy cows decreased milk fat synthesis and appeared to respond
      by partitioning more nutrients toward milk synthesis rather than improving net
      energy balance.

PMID- 14594243
TI  - Dose response of milk fat to intravenous administration of the trans-10, cis-12
      isomer of conjugated linoleic acid.
AB  - Intravenous infusion of conjugated linoleic acid (CLA) was evaluated as a simpler
      method than abomasal infusion and the feeding of calcium salts to examine milk
      fat depression. The objectives were to determine the dose-dependent response of
      milk fat and plasma metabolites to intravenous administration of the trans-10,
      cis-12 isomer of CLA, an isomer identified to possess an inhibitory effect on
      milk fat synthesis. Four multiparous Holstein cows averaging 123 +/- 30 d in milk
      were randomly assigned to treatments in a 4 x 4 Latin square design. Catheters
      were inserted into the jugular vein for infusions and blood sampling. Treatments
      consisted of intravenous infusions of 0, 2, 4, and 6 g/d CLA (> 95% trans-10, cis
      12 CLA). Infusates contained 72 g/d of a parenteral solution, saline, and CLA to
      90 ml. Periods were of 5 d duration with a 7 d wash out. Milk was sampled at each
      milking and analyzed for fat, protein, and fatty acids. Blood samples were
      obtained on the last day of each period. Dry matter intake (22.4 +/- 2.4 kg/d),
      milk yield (28.5 +/- 3.3 kg/d), and protein percent (3.26 +/- 0.08%) of cows were
      not affected by treatment. However, milk fat percentage was reduced linearly with
      increasing doses of CLA. Milk fat percentage was 4.17, 3.53, 3.29, and 2.92% on d
      5 for treatments 0, 2, 4, and 6 g/d CLA, respectively. Concentrations (4.2 mg/g
      of fat) of cis-9, trans-11 CLA in milk fat were not affected by treatment.
      However, an increase in the trans-10, cis-12 CLA content of milk fat was
      observed. Milk fat contained 0.00, 0.02, 0.06, and 0.10 mg of trans-10, cis-12
      CLA per g of fat (SEM = 0.065) for treatments 0, 2, 4, and 6 g/d CLA,
      respectively. Plasma NEFA concentration increased linearly with the dose of the
      trans-10, cis-12 CLA. Intravenous infusion of the trans-10, cis-12 isomer of CLA
      depressed milk fat in a linear manner over the range of infusion studied and,
      therefore, is an alternative to abomasal infusion.

PMID- 14594244
TI  - Milk fatty acid composition of cows fed a total mixed ration or pasture plus
      concentrates replacing corn with fat.
AB  - Thirty-one Holstein cows (six ruminally cannulated) were used to evaluate milk
      fatty acids (FA) composition and conjugated linoleic acid (CLA) content on three
      dietary treatments: 1) total mixed rations (TMR), 2) pasture (Avena sativa L.)
      plus 6.7 kg DM/d of corn-based concentrate (PCorn), and 3) pasture plus PCorn
      with 0.8 kg DM/d of Ca salts of unsaturated FA replacing 1.9 kg DM/d of corn
      (PFat). No differences were found in total (22.4 kg/d) or pasture (18.5 kg/d) dry
      matter intake, ruminal pH, or total volatile fatty acids concentrations. Fat
      supplementation did not affect pasture neutral detergent fiber digestion. Milk
      production did not differ among treatments (19.9 kg/d) but 4% fat-corrected milk
      was lower for cows fed the PFat compared to cows fed the TMR (16.1 vs. 19.5 kg/d)
      primarily because of the lower milk fat percentage (2.56 vs. 3.91%). Milk protein
      concentration was higher for cows fed the TMR than those on both pasture
      treatments (3.70 vs. 3.45%). Milk from the cows fed the PCorn had a lower content
      of short- (11.9 vs. 10.4 g/100 g) and medium-chain (56.5 vs. 47.6 g/100 g) FA,
      and a higher C18:3 percentage (0.07 vs. 0.57 g/100 g) compared with TMR-fed. Cows
      fed the PFat had the lowest content of short- (8.85 g/100 g) and medium-chain
      (41.0 g/100 g) FA, and the highest of long-chain FA (51.4 g/100 g). The CLA
      content was higher for cows in PCorn treatment (1.12 g/100 g FA) compared with
      cows fed the TMR (0.41 g/100 g FA), whereas the cows fed the PFat had the highest
      content (1.91 g/100 g FA). Pasture-based diets increased the concentrations of
      long-chain unsaturated FA and CLA in milk fat. The partial replacement of corn
      grain by Ca salts of unsaturated FA in grazing cows accentuated these changes.
      However, those changes in milk FA composition were related to a depression in
      milk fat.

PMID- 14594245
TI  - Effects of various glucogenic sources on production and metabolic responses of
      dairy cows fed grass silage-based diets.
AB  - Four rumen cannulated Finnish Ayrshire cows in midlactation were used in an
      experiment designed as a 4 x 5 incomplete Latin square with 2-wk periods to
      compare effects of glucogenic substrates on grass silage-based diets. The five
      treatments were continuous infusions of 1) water (control), 2) casein 300 g/d, 3)
      glucose 300 g/d, 4) propionic acid 247 g/d, and 5) barley starch 270 g/d.
      Substrates were infused either into the rumen (propionic acid) or into the
      abomasum (other substrates). As a basal diet, cows were fed a formic acid treated
      grass silage ad libitum (digestible organic matter 690 g/kg dry matter [DM],
      crude protein [CP] 131 g/kg DM) and a barley-rapeseed concentrate (CP 141g/kg DM)
      at a rate of 7 kg/d. Production responses to glucogenic substrates other than
      casein were negligible, suggesting that glucose supply of the cows did not
      primarily limit milk production. However, with casein cows produced significantly
      more milk, milk protein, and lactose than with other glucogenic substrates.
      Casein increased urea and essential amino acid (EAA), and decreased nonessential
      AA (NEAA) in arterial plasma compared with other substrates, suggesting that
      casein provided precursors both in terms of NEAA for gluconeogenesis and EAA for
      milk protein synthesis. This puts forward that providing the AA needs of the
      mammary gland for milk protein synthesis are met, glucose supply may become the
      next limiting factor for milk protein synthesis in cows fed diets based on
      restrictively fermented grass silage. The limited supply of AA from the basal
      diet, and possibly the low production levels of cows partly invalidated the
      hypothesis of monitoring differing glucogenic substrates for grass silage-based
      diets.

PMID- 14594246
TI  - Effects of casein and glucose on responses of cows fed diets based on
      restrictively fermented grass silage.
AB  - This study was conducted to investigate whether well fed dairy cows given
      restrictively fermented grass silage diet will respond to incremental glucose and
      amino acid supply at early stage of lactation. Four rumen-cannulated Finnish
      Ayrshire cows were used in a 4 x 4 Latin square experiment with 14-d periods. The
      cows were fed good quality restrictively fermented grass silage ensiled with a
      formic acid additive for ad libitum intake. A concentrate mixture consisting of
      barley (85%) and solvent extracted rapeseed meal (11.4%) was given at a rate of 9
      kg/d. The four treatments were continuous abomasal infusions of water (control),
      casein 300 g/d, glucose 300 g/d, and casein 300 g/d + glucose 300 g/d. The
      infusions had only minor effects on feed intake, diet digestibility, or rumen
      fermentation pattern. Both casein and glucose infusions increased milk, protein
      and lactose yields the effects being partly additive on the combined infusion.
      Infused casein increased milk protein and urea as well as plasma urea
      concentrations. Both casein and glucose tended to increase plasma glucose
      concentration. Casein increased arterial plasma concentrations of essential amino
      acids (EAA), branched-chain AA (BCAA), and total AA (TAA). Both casein and
      glucose, although glucose usually less than casein, increased arteriovenous
      differences of EAA, nonessential AA, BCAA, and TAA. Extraction efficiencies of AA
      were higher for glucose than for casein. Mammary plasma flow was at highest on
      the control diet, but reduced owing to infused nutrients, the reduction being
      less with combined rather than separate infusions of casein and glucose. Based on
      the partly additive increases in milk production parameters and changes in plasma
      metabolites, it is suggested that glucose alone increased milk protein yield by
      sparing AA from hepatic utilization, while casein increased both supply of AA and
      glucose. It was concluded that cows at early stage of lactation fed diets
      comprising of restrictively fermented grass silage and a cereal-based concentrate
      suffer from both limited AA and glucose supplies.

PMID- 14594247
TI  - Corn silage management: effects of hybrid, maturity, chop length, and mechanical
      processing on rate and extent of digestion.
AB  - Five experiments were conducted to evaluate the effects of hybrid, chop length,
      maturity, and mechanical processing of corn silage on dry matter and nutrient
      disappearance in the rumen. Corn silage that had not been dried or ground was
      incubated in macro in situ bags (30 x 35 cm) for 8, 16, 24,48, and 96 h.
      Experiments la and 2 evaluated the effects of maturity and mechanical processing
      for two corn silage hybrids harvested at two theoretical lengths-of-cut.
      Experiments 3 through 5 evaluated the effects of chop length and mechanical
      processing for two corn silage hybrids harvested at two-thirds milkline. The
      hybrid with low neutral fiber (NDF) concentrations had greater dry matter and
      starch disappearance than the hybrid with high NDF concentrations. The effect of
      chop length on nutrient disappearance was variable across experiments 3 through
      5. Processing improved dry matter disappearance in experiments la, 2 (two-thirds
      milkline and blackline), 3, 4, and 5 at the majority of ruminal incubation
      timepoints. Starch disappearance was greater for unprocessed corn silage in
      experiment la (hard dough and two-thirds milkline) and was greater for processed
      corn silage in experiments 2 and 5. However, there was no consistent trend in
      starch disappearance between processed and unprocessed corn silage in experiments
      3 and 4. This can be partially explained by the high disappearance of starch
      (experiment 3, > or = 98% and experiment 4, > or = 94%) by 24 h of ruminal
      incubation. Minimal differences were detected in NDF disappearance between
      processed and unprocessed corn silage across maturities. In experiments 2 and 5,
      crude protein disappearance was improved due to processing at some incubation
      timepoints. Rate of dry matter, starch (one-third milkline and two-thirds
      milkline), and NDF disappearance tended to increase when corn silage was
      mechanically processed in experiment 2. Dry matter, starch, and crude protein
      disappearance tended to be greater for corn silage harvested at the early
      maturity (one-third milkline) in experiment 2 compared with advanced maturities
      (two-thirds milkline and blackline). Disappearance of NDF was greater at early
      maturities compared with advanced maturities in experiments 1a and 2. Rate of dry
      matter (hybrid 3845), starch, and NDF (hybrid 3845) disappearance tended to
      decrease as maturity advanced from one-third milkline to blackline in experiment
      2. These results suggest that the macro in situ method can be used to evaluate
      nutrient disappearance in the rumen.

PMID- 14594248
TI  - Utilization of phosphorus in lactating cows fed varying amounts of phosphorus and
      forage.
AB  - The objective of this study was to determine the effect of dietary forage
      proportion and P content on fecal P excretion. Four dietary treatments were
      formed in a 2 x 2 factorial arrangement. The P content was 0.33 or 0.42%, and the
      forage proportion was 48 or 58% on a dry matter (DM) basis. The neutral detergent
      fiber content was 27 and 30% for the low and high forage diets, respectively. The
      P amount was varied by using monosodium phosphate, and the forage amount by
      changing the proportions of alfalfa silage and corn. The diets were fed to 44
      midlactation Holsteins for 14 wk. Fecal P excretion was estimated using Cr marker
      and grab sampling. Dietary P content did not affect DM intake, milk yield, or
      milk composition. The P intake averaged 74 and 96 g/d and fecal P averaged 0.69
      and 0.92% (DM basis) or 49 and 65 g/d for the low and high P diets, respectively.
      Thus, reducing dietary P from 0.42 to 0.33% resulted in approximately 25% less
      estimated fecal P excretion. Increasing dietary forage reduced milk yield (34.0
      vs. 36.5 kg/d), but increased milk fat content (3.66 vs. 3.25%). Estimated
      apparent digestibility of P tended to decrease (31.1 vs. 36.6%) when the forage
      proportion increased, but most of the change occurred when the diets contained
      the low amount of P. Overall, the effect of forage proportion on estimated fecal
      P excretion was small when diets contained 48 or 58% forage, varied by alfalfa
      silage. Phosphorus intake has a much larger impact on fecal P excretion than
      forage proportion, and it does not seem necessary to adjust the dietary P content
      according to the forage proportion to provide the same amount of absorbed P.

PMID- 14594249
TI  - Effects of dietary amino acid balance on the response of dairy cows to an
      increase of milking frequency from twice to three times daily.
AB  - An experiment was conducted to examine how the response of dairy cows to a change
      from twice to three times-daily milking is affected by deficiencies in the
      dietary supplies of three amino acids, His, Met, and Lys. Six cows were used in a
      6 x 6 Latin square with 14-d periods. The three dietary treatments were: grass
      silage and a cereal-based supplement containing feather meal as the sole protein
      supplement; the same silage-cereal diet supplying similar amounts of
      metabolizable and rumen-undegradable protein but with additional amounts of His,
      Met, and Lys in the form of fish meal; and the fish meal diet with additional
      metabolizable energy in the form of an additional 2 kg/d of sugar beet pulp.
      Within each of these dietary treatments, the cows were milked twice and three
      times daily, making a total of six treatments. When cows were given the feather
      meal diet, even though dietary metabolizable energy was in considerable excess, a
      deficiency of specific amino acids prevented any increase in milk yield in
      response to increasing the frequency of milking from twice to three times daily.
      In contrast, when cows consumed a similar level of excess metabolizable energy
      and a similar level of rumen-undegradable protein for which the protein was of
      better amino acid balance (fish meal), the increased frequency of milking led to
      increased yield of milk and milk protein.

PMID- 14594250
TI  - C-reactive protein and antibacterial activity in blood plasma of colostrum-fed
      calves and the effect of lactulose.
AB  - Several milk proteins are very important for immunological defense and can be
      absorbed in the intestine of calves in the first hours after birth. The influence
      of colostrum intake and the effect of additional lactulose application on the
      concentration of C-reactive protein (CRP) in blood were investigated. The CRP is
      known as a mediator of innate immunity. Results were compared to the bovine acute
      phase protein haptoglobin, and to lactalbumin, lactoferrin, and immunoglobulins
      in plasma from calves. After colostrum intake, the concentration of most proteins
      were strongly increased. The data show, for the first time, a significant
      increase of CRP in the blood of calves 1 d after colostrum intake (nonlactulose
      group, n = 10), and an even more significant increase in CRP concentration (1 d
      postpartum) was measured in the group of animals with additional application of
      lactulose (lactulose group, n = 10) when compared to the nonlactulose group. In
      an in vitro assay with the plasma of these animals, an increased bactericidal
      activity was detected against Morganella morganii (1 d postpartum) in both
      groups, but again a higher activity occurred in the lactulose group. The results
      of these investigations emphasize the importance of colostrum intake during the
      first hours after birth for the defense potential of newborn calves. In addition,
      lactulose may have a positive effect in the period of passive transfer of
      colostrum proteins and in the immune defense.

PMID- 14594251
TI  - Cell proliferation, apoptosis, and B- and T-lymphocytes in Peyer's patches of the
      ileum, in thymus and in lymph nodes of preterm calves, and in full-term calves at
      birth and on day 5 of life.
AB  - Peyer's patches, thymus, and lymph nodes contain the majority of lymphocytes. We
      have studied proliferation rates, apoptosis rates, and numbers of B- and T
      lymphocytes in Peyer's patches in ileum, thymus, and mesenterial and prescapular
      lymph nodes (LM and LP) in unfed preterm calves (GrP; born 13 d before expected
      normal term after dams were injected with prostaglandin F2alpha and
      glucocorticoids) and normal-term calves (GrF) immediately after birth and on d 5
      of life after feeding colostrum for 4 d (GrC). Immunohistochemical methods in
      conjunction with incorporation of 5-bromo-2'-deoxyuridine or terminal
      deoxynucleotidyl transferase-mediated X-dUTP nick end labeling were used to
      evaluate cell proliferation rates and apoptosis rates, respectively. The number
      of T- and B-lymphocytes was determined with monoclonal antibodies directed
      against CD3 and CD79, respectively. In GrF compared with GrP, there were higher
      numbers of proliferating and apoptotic cells in LM and LP, of B-lymphocytes in
      paracortex and follicles of LM and LP, and of proliferating cells in cortex and
      medulla of thymus. In thymus cortex and medulla, numbers of proliferating cells
      were higher in GrC than in GrF. Apoptotic rates were generally smaller at all
      sites of Peyer's patches in GrC than in GrF, and proliferation rates increased
      from GrP to GrF in intrafollicular areas and from GrF to GrC in all tissues.
      Numbers of T-lymphocytes in Peyer's patches were higher in GrF than in GrP, but
      lower in GrC than in GrF, except in the domes. Numbers of B-lymphocytes did not
      change in Peyer's patches despite high proliferation and low apoptotic rates,
      suggesting that they leave Peyer's patches during the first days of life. In
      conclusion, proliferation and apoptosis rates and numbers of B- and T-
      lymphocytes in Peyer's patches in ileum, thymus, and LM and LP exhibited
      different developmental changes and were affected by feeding.

PMID- 14594252
TI  - Effect of sarsaponin on ruminal fermentation with particular reference to methane
      production in vitro.
AB  - This experiment was designed to investigate the effects of different
      concentrations (0, 1.2, 1.8, 2.4, and 3.2 g/L) of sarsaponin on ruminal microbial
      methane production using the substrates soluble potato starch, cornstarch, or hay
      plus concentrate (1.5:1). Ruminal fluid was collected from a dairy cow, mixed
      with phosphate buffer (1:2) and incubated (30 ml) anaerobically at 38 degrees C
      for 6 and 24 h with or without sarsaponin. Excluding the lower level of
      sarsaponin, pH of the medium was slightly decreased. Ammonia-N concentration and
      numbers of protozoa were decreased in a dose-dependent manner. Total volatile
      fatty acids and total gas production were increased. Molar proportion of acetate
      was decreased and propionate was increased with a corresponding decrease in
      acetate:propionate ratio. Hydrogen production was decreased. As the concentration
      of sarsaponin increased from 1.2 to 3.2 g/L, fermentation of soluble potato
      starch, cornstarch, or hay plus concentrate decreased methane production from 20
      to 60% (6 h) and 17 to 50% (24 h), 21 to 58% (6 h) and 18 to 52% (24 h), and 23
      to 53% (6 h) and 15 to 44% (24 h), respectively. Excluding the lower dose
      concentration (1.2 g/L) of sarsaponin, in vitro disappearance of dry matter of
      hay plus concentrate was decreased after 24 h. In conclusion, these results show
      that sarsaponin stimulated the mixed ruminal microorganism fermentation as well
      as to inhibit methane production in vitro.

PMID- 14594253
TI  - In situ evaluation of hen mortality meal as a protein supplement for dairy cows.
AB  - A study was conducted to evaluate the nutritional composition and in situ
      degradation of hen mortality meals. There were four treatments: control
      autoclaved hen meal (C-HM), enzyme-treated, fermented, autoclaved hen meal (E
      HM), NaOH-treated, fermented, autoclaved hen meal (NaOH-HM), and soybean meal
      (SBM). For the E-HM or NaOH-HM, hen mortality was treated with a feather
      digesting enzyme or NaOH to improve digestibility of feathers on the carcass.
      After the enzyme or NaOH treatment, treated hen mortality was preserved by a
      fermentation procedure. The crude protein levels of the C-HM and SBM were higher
      than the E-HM and NaOH-HM, and the concentration of fat in the C-HM was higher
      than the other treatments. Levels of Lys, Thr, Arg, Ile, Leu, Val, and Phe for
      the C-HM and SBM were higher than in the E-HM and NaOH-HM. The Met, Cys, and Gly
      levels in the C-HM were higher than the soybean meal. In situ ruminal degradation
      data showed that the C-HM had lower dry matter and crude protein degradation than
      the other treatments, whereas the E-HM or NaOH-HM was more susceptible to ruminal
      degradation. These results indicate that the C-HM has higher levels of crude
      protein, amino acids, and resistance to ruminal degradation, whereas the E-HM or
      NaOH-HM was more digestible to ruminal microorganisms.

PMID- 14594254
TI  - The effect of corn silage particle size on eating behavior, chewing activities,
      and rumen fermentation in lactating dairy cows.
AB  - The objective of this experiment was to evaluate effects of reducing corn silage
      particle size on eating behavior, chewing activity, and rumen fermentation in
      lactating dairy cows. Four cannulated, multiparous cows averaging 110 +/- 4 d in
      milk and weighing 675 +/- 70 kg were randomly assigned to a 4 x 4 Latin square.
      During each of four 14-d periods, animals were offered one of four diets that
      were chemically similar but varied in corn silage particle size: short (SH),
      mostly short (MSH), mostly long (MLG), and long (LG), with a geometric mean
      particle length of 7.4, 7.8, 8.3, and 8.8 mm, respectively. Reducing particle
      size increased dry matter intake (DMI) linearly (28.0, 26.8, 26.8, and 25.7 kg/d
      for SH, MSH, MLG, and LG respectively). At 8, 16, and 24 h postfeeding, the
      neutral detergent fiber (NDF) concentration of feed remaining in the bunk
      decreased linearly with reduced particle size. Time spent eating or ruminating
      was not different across treatments; however, total chewing activity (TC; sum of
      time spent eating and ruminating) exhibited a quadratic response with highest
      chewing activities observed for diets with shortest and longest particle size.
      Eating or ruminating time per kilogram of DMI was not affected by corn silage
      particle size, but TC per kilogram of DMI decreased linearly with decreasing
      particle size. In comparison, when expressed as minutes per unit of NDF intake
      (NDFI), ruminating, and TC were linearly reduced as particle size decreased.
      Rumen pH was not affected by corn silage particle size even though total
      concentration of volatile fatty acids increased linearly from 89.1 mM/L to 93.6
      mM/L as diet particle size decreased. A quadratic effect was observed in molar
      proportion of acetate and propionate with the highest concentration observed in
      animals consuming diets of intermediate particle size. Results of this experiment
      suggest that reducing corn silage particle size may increase DMI, positively
      affect rumen fermentation, and reduce sorting behavior. Because both chewing
      activity and sorting tendencies increased when proportion of TMR particles > 19.0
      mm increased, results suggest that particle size measurement as estimated by the
      PSPS is useful in understanding some factors that affect feeding behavior.

PMID- 14594255
TI  - Measuring the feeding behavior of lactating dairy cows in early to peak
      lactation.
AB  - The objectives of this study were to: 1) objectively define meal criteria
      (minimum interval between meals) of free-stall housed cows fed via a feed alley,
      2) determine which measures of feeding behavior were most repeatable, and 3)
      describe changes in the feeding behavior from early to peak lactation. An
      electronic monitoring system was used to record individual cow presence (hits; 6
      s resolution) at the feed alley for 21 lactating cows for three 8-d periods:
      period 1, 35 +/- 16 (mean +/- SD), period 2, 57 +/- 16, and period 3, 94 +/- 16
      DIM. A mixture distribution model was used to calculate the meal criterion (27.74
      min) by fitting the log10 frequency distribution of the intervals between hits.
      The within-cow repeatability was highest for feeding activity (hits d(-1)) and
      intensity (hits per meal min), moderate for total daily mealtime (min d(-1)) and
      meal duration (min meal(-1)), and lowest for meal frequency (meals d(-1)). From
      periods 1 to 2, all cows showed increases in total daily mealtime, meal
      frequency, and meal duration; however, cows with lower meal frequencies and
      feeding intensity in period 1 showed the greatest increases. Cows with high
      feeding activity and intensity during period 2 showed proportionally greater
      increases during period 3. These results illustrate that some measures of feeding
      behavior are highly repeatable within cows, but variable between cows and across
      stages of lactation. Thus, tests of treatment effects on feeding behavior should
      be within cow and control for days in milk.

PMID- 14594256
TI  - Technical note: DNA typing for ovine MHC DRB1 using polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP).
AB  - The ovine major histocompatibilty complex (Ovar) class II DRB1 second exon was
      amplified by polymerase chain reaction (PCR) from DNA samples of 52 Suffolk
      sheep. Polymerase chain reaction products were characterized by the restriction
      fragment length polymorphism (RFLP) technique using nine restriction enzymes,
      RsaI, HaeIII, SacI, SacII, DdeI, NciI, Hin1I, EcoRI, and BstNI, yielding 13
      types. Sequencing of cloned PCR products identified 16 Ovar-DRB1 alleles.
      Collectively, all PCR-RFLP patterns exactly matched those predicted from DNA
      sequences. These findings strongly indicate that the PCR-RFLP method using a
      combination of nine restriction endonucleases is a very powerful tool in Ovar
      typing.

PMID- 14594257
TI  - Implementation of a sire-maternal grandsire model for evaluation of calving ease
      in the United States.
AB  - The objective of this study was to add a maternal grandsire (MGS) effect to the
      existing sire model for national calving ease genetic evaluations. The Animal
      Improvement Programs Laboratory (AIPL) of USDA assumed responsibility for
      conducting the national genetic evaluation for calving ease and maintaining the
      associated database in 1999. Existing evaluations used a sire threshold model.
      Adding an MGS effect to the model was expected to improve accuracy by partially
      accounting for merit of mates and differences in maternal ability of the dams.
      Dystocia data were migrated to a relational database integrated with the AIPL
      production database. This database design allowed more rigorous data edits by
      comparison with the production data and improved MGS identification (ID) rate by
      utilizing pedigrees from the production records. Integration of dystocia data
      with production data increased MGS ID rate from 58 to 73%. In addition, nearly
      200,000 duplicate records were identified using the new edit system. Sire and
      sire-MGS models were compared using over 10 million observations available for
      the August 2002 national genetic evaluation. The sire model included herd-year,
      season, sex of calf, parity of dam, birth year group of sire, and sire. For the
      sire-MGS model, MGS and birth year group of MGS were added, year-seasons rather
      than seasons were used, and sex of calf and parity of dam were combined into a
      single interaction effect. Herd-year, sire, and MGS were random effects. Variance
      components used for the sire model were those previously used in the national
      evaluation and for the sire-MGS model were estimated in a separate study.
      Correlations between predicted genetic merits for service sire calving ease from
      the two models was 85%, indicating general agreement, but with some significant
      differences in evaluations. A sire-MGS model was implemented in August 2002 for
      the national calving ease genetic evaluation system.

PMID- 14594258
TI  - Assessment of homogeneity vs. heterogeneity of residual variance in random
      regression test-day models in a Bayesian analysis.
AB  - Test-day first-lactation milk yields from Holstein cows were analyzed with a set
      of random regression models based on Legendre polynomials of varying order on
      additive genetic and permanent environmental effects. Homogeneity and
      heterogeneity of residual variance, assuming three and 30 arbitrary measurement
      error classes of different length were considered. Unknown parameters were
      estimated within a Bayesian framework. Bayes factors and a checking function for
      the cross-validation predictive densities of the data were the tools chosen for
      selecting among competing models. Residual variances obtained from 30 arbitrary
      intervals were nearly constant between d 70 and 300 and tended to increase
      towards the extremes of the lactation, especially at the onset. In early
      lactation, the temporary measurement errors were found to be larger and highly
      variable. A high order of the regression submodels employed for modeling the
      permanent environmental deviations tended to strongly correct the heterogeneity
      of the residual variance. Accordingly, the assumption of homogeneity of residual
      variance was the most plausible specification under both comparison criteria when
      the number of random regression coefficients was set to five. Otherwise, the
      heterogeneity assumption, using three or 30 error classes, was better supported,
      depending on the criterion and on the order of the submodel fitted for the
      permanent environmental effect.

PMID- 14594259
TI  - Progeny testing and selection intensity for Holstein bulls in different
      countries.
AB  - International Bull Evaluation Service (Interbull) Holstein evaluations from
      February 1995 through February 2003 were used to determine characteristics of
      progeny testing for Holstein bulls in Australia, Canada, Denmark, France,
      Germany, Italy, New Zealand, Sweden, The Netherlands, and the United States. The
      decision to graduate a bull from progeny test (PT) was assumed to have been made
      based on the second Interbull evaluation, and graduation was defined as the
      addition of 200 daughters in the period 2.5 to 4.5 yr later. Mean bull age at PT
      decision varied across countries by 12 mo. Mean numbers of herds and daughters
      ranged from 39 to 111 and 54 to 144, respectively. Countries with higher
      requirements for official evaluations generally had more herds and daughters but
      older bulls at PT decision. Mean estimated breeding values for yield traits of
      sires of tested bulls were most similar across countries for fat, differing by
      only 6.4 kg. The four countries highest for sire protein differed only by 1 kg;
      however, the range was 12 kg. Percentages of bulls graduated ranged from 4.4 to
      14.7 across countries. Selection intensities (standardized selection
      differentials) tended to be about 1.0 for yield traits. Selection intensities for
      somatic cell score were generally unfavorable, reflecting selection for
      negatively correlated yield traits. Reflecting variation in national breeding
      goals, selection intensities for stature were positive for most countries and
      highly negative for New Zealand. Selection intensity for fore udder was generally
      the lowest among the traits examined. All but one country showed positive
      selection for udder support. These statistics permit comparison of the components
      of PT programs across country, illustrating possible opportunities for
      improvement.

PMID- 14594260
TI  - Radicals with a controlled lifestyle.

PMID- 14594261
TI  - Synthetic multifunctional pores: lessons from rigid-rod beta-barrels.
AB  - In this account, studies on synthetic multifunctional pores formed by rigid-rod
      beta-barrels are summarized comprehensively. The first section outlines the
      evolution of synthetic multifunctional pores from the introduction of rigid-rod
      molecules in bioorganic chemistry and the discovery of synthetic beta-barrels in
      comparison with pertinent developments in related areas of research. Design
      strategies to position active sites at the inner surface of rigid-rod beta-barrel
      pores are described in the second section. The third section focuses on the
      characteristics of transmembrane barrel-stave pores, emphasizing the dynamic
      nature of supramolecular oligomers with the aid of notional phase and energy
      diagrams. Section four introduces multifunctionality with the use of synthetic
      pores as hosts of a rich collection of guests, reaching from inorganic cations to
      organic macromolecules like peptides, oligonucleotides, polysaccharides and
      polyacetylenes. In section five, practical applicability of molecular recognition
      by synthetic multifunctional pores is documented with non-invasive fluorometric
      enzyme sensing. The application of host-guest chemistry within synthetic pores to
      couple molecular recognition and translocation with molecular transformation is
      the topic of section six. The last section mentions some perspectives and
      challenges with synthetic multifunctional pores.

PMID- 14594262
TI  - Dendronized cyclocopolymers with a radial gradient of polarity and their use to
      catalyze a difficult esterification.
AB  - A cyclocopolymer containing pyrrolidinopyridine pendant groups was dendronized
      with polyester dendrons terminated with long alkyl chain ends and the
      microenvironment created by the dendrons was used to catalyze the difficult
      esterification of a tertiary alcohol with pivalic anhydride.

PMID- 14594263
TI  - Self-assembly of an unpolar enantiomerically pure helicate-type metalla-cryptand.
AB  - Chiral tetraketone ligands are obtained by Claisen-type condensation of 4
      bromoacetophenone with the acetone ketal of L-tartraic acid diethylester and lead
      with gallium(III) or iron(III) ions in self-assembly processes to dinuclear
      helicate-type cryptands which are able to bind lithium cations.

PMID- 14594264
TI  - Unusual flexibility of 2,5-bis(4-pyridylethynyl)thiophene self-assembled with
      Co(NCS)2 in a novel coordination polymer.
AB  - A novel coordination polymer containing Co(NCS)2 and a rigid ligand, 2,5-bis(4
      pyridylethynyl)-thiophene showing unusual flexibility was synthesized.

PMID- 14594265
TI  - Novel UV cured coatings and adhesives based on the photoinitiated
      cyclopolymerization of derivatives of diallylamine.
AB  - A new family of non-acrylate UV cured three-dimensional polymeric networks for
      coatings and adhesives based on the photoinitiated cyclopolymerization of
      diallylamine salts and diallylamides using a low power (75 W) UVA domestic
      sunlamp is described.

PMID- 14594266
TI  - Quantum dot-labelled polymer beads by suspension polymerisation.
AB  - CdSe quantum dots with polymerisable ligands have been incorporated into
      polystyrene beads, via a suspension polymerisation reaction, as a first step
      towards the optical encoding of solid supports for application in solid phase
      organic chemistry.

PMID- 14594267
TI  - Novel conformationally-constrained beta-peptides characterized by 1H NMR chemical
      shifts.
AB  - For a novel family of oxanorbornene beta-peptides, density functional theory
      computations of the three-dimensional structure and 1H NMR chemical shifts
      predict that the dimer and trimer form consecutive 8-membered hydrogen-bonded
      ring helices, which is supported by excellent agreement with experimental
      solution NMR data.

PMID- 14594269
TI  - Retardation of oil drop evaporation from oil-in-water emulsions.
AB  - The rate of evaporation of volatile oils from oil-in-water emulsions can be
      strongly retarded by using a polymeric emulsion stabiliser instead of a low molar
      mass surfactant.

PMID- 14594268
TI  - Solution complexation between potassium iodide and lariat ethers having pi-donor
      sidearms.
AB  - Experimental evidence is presented for the interaction of triple bond pi-donors
      with potassium cation in acetonitrile solution.

PMID- 14594270
TI  - Novel emulsions of ionic liquids stabilised solely by silica nanoparticles.
AB  - We have successfully prepared a series of novel stable emulsions, of both simple
      and multiple types, containing ionic liquids and stabilised solely by silica
      nanoparticles.

PMID- 14594271
TI  - Synthesis of highly nitrogen-doped multi-walled carbon nanotubes.
AB  - We present a new synthesis route for nitrogen doped carbon nanotubes (CNx) based
      on the aerosol method. Tubes with a record high concentration of nitrogen
      (approximately 20 atom%) have been synthesized, confirmed by electron energy loss
      spectroscopy (EELS). A strong correlation between the N/C ratio and morphology of
      the tubes is observed and discussed.

PMID- 14594272
TI  - 3D porous and 3D interpenetrating triple framework structures constructed by
      aurophilicity-coordination interplay in [Mn[Au(CN)2]2(H2O)2]n and
      [KFe[Au(CN)2]3]n.
AB  - Two cyano-bridged heterobimetallic coordination polymers [Mn[Au(CN)2]2(H2O)2]n
      (1) and [KFe[Au(CN)2]3]n (2), have been synthesized from [Au(CN)2]- building
      blocks and structurally characterized. In both complexes aurophilicity play an
      important role in determining the 3D open microporous framework and the
      interpenetrating triple framework for 1 and 2, respectively. Both aqueous
      solutions of 1 and 2 display interesting luminescent properties.

PMID- 14594273
TI  - O-H bond elongation in co-ordinated water through intramolecular P=O...H-O
      bonding. 'Snap-shots' in phosphate ester hydrolysis.
AB  - Molecular structure of [Cu(dtbp)2(phen)(OH2)] (dtbp-H = di-tert-butylphosphate,
      phen = 1,10-phenanthroline), determined at 293, 203 and 93 K, provides useful
      snap-shots of O-H bond activation of a metal-bound water, which is aided by an
      intramolecular P=O...H-O hydrogen bonding interaction.

PMID- 14594274
TI  - Synthesis, solid state structure and polymerisation of a fully planar
      cyclopentadithiophene.
AB  - The new fully planar cyclopentadithiophene, 4-n-dodecylidene-4H-cyclopenta(2,1
      b;3,4-b')dithiophene, shows extensive pi-stacking in the solid state with short
      intermolecular distances (ca. 3.5 A) between adjacent molecules. Polymerisation
      of this monomer by two different protocols gave solution processable alkenyl
      bridged cyclopentadithiophene polymers with extended pi-conjugation in the main
      chain.

PMID- 14594275
TI  - A stereoselective synthesis of anti-gamma,delta-alkynyl- and -alkenyl-beta
      hydroxy-alpha-amino esters from tin(II) enolates of glycinate.
AB  - Condensations between the tin(II) enolate 11 of ethyl N-tosylglycinate and
      conjugated ynals 12 and ynones 14 are highly diastereoselective, in favour of the
      anti-isomers 13 and 15; similar reactions of enals and enones 17 show lower but
      still useful levels of anti-stereoselectivity.

PMID- 14594276
TI  - Lewis acid mediated cyclisations of silylated methylenecyclopropyl hydrazones.
AB  - Silylated methylenecyclopropyl hydrazones on treatment with BF3 x Et2O cyclise to
      give heterocyclic products involving a novel sequence of hydride and silyl shifts
      via a series of increasingly stable cationic intermediates.

PMID- 14594277
TI  - Chiral tris(oxazoline)/Cu(II) catalyzed coupling of terminal alkynes and
      nitrones.
AB  - Novel chiral iPr-tris(oxazoline)/Cu(ClO4)2 x 6H2O catalyzed coupling of terminal
      acetylenes and nitrones to afford cis-disubstituted beta-lactams is described;
      the choice of base proves essential to both the diastereoselectivity and the
      enantioselectivity.

PMID- 14594278
TI  - On the water promoted reaction of titanium isopropoxide with carbon dioxide.
AB  - Insertion of carbon dioxide into titanium isopropoxide takes place only in the
      presence of trace quantities of water to give an isopropyl carbonato cluster
      which has been crystallographically characterised.

PMID- 14594279
TI  - Solution structure and stability of a disulfide cross-linked nucleopeptide
      duplex.
AB  - NMR methods are used to study the structure and stability of the duplex formed by
      the nucleopeptide [Ac-Cys-Gly-Ala-Hse(p3'dGCATGC)-Ala-OH]2[S-S], in which the
      oligonucleotide is self-complementary and the cysteine residues of the two
      peptide chains form a disulfide bridge; thermal transitions and NMR-derived
      structural calculations are consistent with a 3-D structure in which the
      oligonucleotide forms a standard B-DNA helix without significant distortions; the
      peptide chains are relatively disordered in solution and lie in the minor groove
      of the DNA helix; this nucleopeptide duplex exhibits a high melting temperature,
      indicating that peptide-oligonucleotide conjugates containing cysteines are
      suitable molecules to establish cross-links between DNA strands and stabilize the
      duplex.

PMID- 14594280
TI  - Biorecognition-modulated ion fluxes through functionalized gold nanotubules as a
      novel label-free biosensing approach.
AB  - A novel biosensing principle is presented, based on the potentiometric monitoring
      of an indicator ion such as Ca2+, whose zero-current flux through chemically
      modified nanochannels is altered by biorecognition events.

PMID- 14594281
TI  - Polyoxometalates covalently bonded with terpyridine ligands.
AB  - A terpyridine ligand is covalently linked to a hexamolybdate cluster through the
      Mo-N imido bond, paving the way for the preparation of hybrids containing
      covalently bonded transition metal complexes and polyoxometalate clusters.

PMID- 14594282
TI  - A novel tailored bimodal porous silica with well-defined inverse opal
      microstructure and super-microporous lamellar nanostructure.
AB  - A novel tailored bimodal porous silica with well-defined inverse opal
      microstructure and super-microporous lamellar nanostructure has been successfully
      synthesized by simultaneous application of three-dimensional order polystyrene
      (PS) beads and an amphiphilic ionic liquid (AIL) as templates.

PMID- 14594283
TI  - Chiral anilines: development of C2-symmetric, late-transition metal catalysts for
      isoselective 2-butene polymerization.
AB  - Chiral nickel catalysts were synthesized and used for the isoselective
      polymerization of trans-2-butene.

PMID- 14594284
TI  - One-pot surfactant assisted synthesis of aluminosilicate macrochannels with
      tunable micro- or mesoporous wall structure.
AB  - A one-step surfactant assisted synthesis pathway was developed leading to novel
      hierarchical macro-meso- (or micro-)porous aluminosilicates made of an assembly
      of macrochannels with openings between 0.5 and 2.0 microm and wormhole-like
      amorphous walls with tunable pore sizes.

PMID- 14594285
TI  - An efficient and inexpensive catalyst system for the aza-Michael reactions of
      enones with carbamates.
AB  - A new strategy which uses very cheap FeCl3 as an effective catalyst in the
      presence of Me3SiCl has been developed for the conjugate addition of enones and
      chalcone with unactivated weakly nucleophilic carbamates.

PMID- 14594286
TI  - CdSe-filled silica nanotubes.
AB  - The novel nanostructures, CdSe-filled silica nanotubes with diameter about 100 nm
      and length up to several micrometres, were synthesized through a simple
      thermochemistry method. CdSe nanorods inside the nanotubes are structurally
      uniform and single crystalline growing along the < 100 > direction.

PMID- 14594287
TI  - Gadolinium-binding helix-turn-helix peptides: DNA-dependent MRI contrast agents.
AB  - A de novo designed gadolinium metallopeptide was found to be a very efficient
      relaxation agent, with 100% increase in relaxivity upon binding to DNA.

PMID- 14594288
TI  - Anion recognition by functionalized single wall carbon nanotubes.
AB  - Amidoferrocenyl-functionalised single wall carbon nanotubes (Fc-SWNT) are
      efficient exoreceptors for the redox recognition of H2PO4-.

PMID- 14594289
TI  - Stereoselective synthesis of tetrahydropyran-3-ones by rearrangement of oxonium
      ylides generated from metal carbenoids.
AB  - The synthesis of tetrahydropyran-3-ones by copper-catalysed reactions of diazo
      ketone tethered allylic ethers has been explored. Product distribution can be
      explained by the intermediacy of a free ylide or direct rearrangement of a metal
      bound ylide equivalent.

PMID- 14594290
TI  - A novel nonlinear optically active tubular coordination network based on two
      distinct homo-chiral helices.
AB  - A novel tubular coordination network [Zn(spcp)(OH)] (spcp = 4-sulfanylmethyl-4'
      phenylcarboxylate pyridine) with a modest SHG activity based on two types of homo
      chiral helices was synthesized and characterized.

PMID- 14594292
TI  - Synthesis of ultrahigh-density ordered arrays of metallic nickel nanowires in
      mesoporous silica films.
AB  - Two-dimensional (2D) mesoporous silica films were employed as a template to
      fabricate ultrahigh-density ordered arrays of metallic nickel nanowires via
      electroless deposition.

PMID- 14594291
TI  - Beta-lactams or gamma-lactams by 4-exo-trig or 5-endo-trig anionic cyclisation of
      lithiated acrylamide derivatives.
AB  - Substituted acrylamide derivatives of benzylamine are lithiated alpha to nitrogen
      by LDA. The benzyllithium thus formed undergoes either 5-endo-trig anionic
      cyclisation, formally by intramolecular conjugate addition to the acrylamide, to
      yield 5-membered lactams, or, if the acrylamide bears a beta-electron withdrawing
      group, 4-exo-trig cyclisation to a beta-lactam.

PMID- 14594293
TI  - Synthesis and inclusion properties of a novel macrocyclic hexaketone monohydrate
      with a hemiacetal structure.
AB  - A macrocyclic hexaketone monohydrate was synthesized by the oxidation of either
      tribenzohexadehydro[12]annulene or tribenzotetradehydro[12]annulene-1,2-dione
      with ruthenium catalysts; the hexaketone monohydrate incorporates small molecules
      with a hydroxy, carbonyl or ether group in the crystalline lattice to form
      inclusion complexes.

PMID- 14594294
TI  - Mechanistic insight into the lanthanide(III) salt catalysed monoacylation of
      symmetrical diols from structural models.
AB  - Model studies are presented that suggest the mechanism of the lanthanide(III)
      salt catalysed mono acylation of symmetrical diols proceeds via chelation of the
      diol and the anhydride to the lanthanide salt, followed by an 'intramolecular'
      acyl transfer.

PMID- 14594295
TI  - Instantaneous, stoichiometric generation of powerfully reducing states of protein
      active sites using Eu(II) and polyaminocarboxylate ligands.
AB  - Addition of an equivalent of a polyaminocarboxylate ligand (L) to a solution of a
      redox protein and the aqua Eu2+ ion results in the instantaneous in situ
      generation of a very powerful reductant Eu(II)-L that can rapidly drive an
      electron stoichiometrically onto a redox centre having an extremely negative
      reduction potential (lower than -1 V): this is exemplified by straightforward
      generation of the super-reduced state of the Fe-protein of nitrogenase.

PMID- 14594296
TI  - Stereospecific and efficient alkynylation at the more hindered carbon of
      trisubstituted epoxides.
AB  - The stereospecific and regioselective C(3) alkynylation of trisubstituted
      epoxides has been achieved with lithium alkynyl trimethylaluminium ate complexes
      in the presence of BF3 x OEt2.

PMID- 14594297
TI  - A novel four-component reaction for the synthesis of functionalised
      dihydropyrimidines.
AB  - In a multi-component reaction (MCR) of a phosphonate, nitriles, aldehydes and
      isocyanates, N3-functionalised dihydropyrimidines can be synthesised efficiently
      via a Horner-Emmons/aza Diels-Alder pathway.

PMID- 14594298
TI  - A novel 1,3,5-tris(alpha,beta,beta-trifluorovinyl)benzene monomer.
AB  - The reaction of the perfluoroalkenylzinc reagent, CF2=CFZnBr, with 1,3,5
      tribromobenzene in the presence of a catalytic amount of Pd(Ph3)4 yielded a novel
      trifunctional monomer 1,3,5-tris(alpha,beta,beta-trifluorovinyl)benzene (1).

PMID- 14594299
TI  - Highly diastereoselective reduction of ferrocene bis-imines with methyllithium
      and the formation of C2-symmetric Zr complexes.
AB  - Alkylation of ferrocene bis-imines Fc[N=C(H)Ar]2 (Ar = Ph, p-Tol) with MeLi was
      found to proceed in a highly diastereoselective fashion producing the C2
      symmetric ferrocene diamines Fc[NC(H)(Me)Ar]2-H2 with 90% diastereomeric excess.
      This process allowed for the synthesis of C2-symmetric zirconium complexes
      Fc[NC(Me)Ar]ZrBn2.

PMID- 14594300
TI  - Synthesis and immobilization of quaternary ammonium cations in acidic zeolites.
AB  - A general method for the synthesis of quaternary ammonium cations in acidic
      zeolites by a direct reaction of tertiary amines and alcohols is described.

PMID- 14594301
TI  - Catalytic enantioselective transamination of alpha-keto esters: an organic
      approach to enzymatic reactions.
AB  - The half-transamination reaction of alpha-keto esters with pyridoxamine or 4
      picolylamine was found to be catalysed by different metal catalysts in organic
      solvents giving moderate yields and enantioselectivities of up to 37% ee for
      methyl-3-indole pyruvate.

PMID- 14594302
TI  - Rapid cleavage of the naphthylmethyl-oxygen bond in higher triplet excited
      states.
AB  - Rapid cleavage of the naphthylmethyl-oxygen bond of 1- and 2-[(4
      benzoylphenoxy)methyl]naphthalenes in higher triplet excited states occurred
      within a laser flash of 5 ns to give 1- and 2-naphthylmethyl radicals with
      formation quantum yields of 0.042 +/- 0.004 and 0.020 +/- 0.002, respectively,
      during two-colour two-laser flash photolysis.

PMID- 14594303
TI  - Two prolines with a difference: contrasting stereoelectronic effects of 4R/S
      aminoproline on triplex stability in collagen peptides [pro(X)-pro(Y)-Gly]n.
AB  - 4R/S-Aminoprolines when present in the X-position of collagen peptide [pro(X)
      pro(Y)-Gly]n exhibit pH- and stereochemistry-dependent effects on triplex
      stability.

PMID- 14594304
TI  - Synthesis of the first fluoro(phosphanyl)- and diphosphanyl-stannanes and
      surprising formation of [P(SnMe3)4]+ SiF5-.
AB  - Monophosphanylation of the difluorostannane Is2SnF2 (Is = 2,4,6
      triisopropylphenyl) with Si(PH2)4 furnishes the first isolable
      fluoro(phosphanyl)stannane Is2Sn(F)PH2 1, which readily undergoes unique SiO2
      assisted decompostion to [Is2Sn(PH)]2 2 and HF, while further phosphanylation of
      1 leads to the remarkably stable diphosphanylstannane Is2Sn(PH2)2 3; the latter
      reacts with Me3SnF at the glass-wall to give the first perstannylphosphonium
      pentafluorosilicate [P(SnMe3)4]+ SiF5- 4.

PMID- 14594305
TI  - An EPR study of the intramolecular dynamics in o-semiquinonic nickel complexes
      with a diphosphorous pincer ligand.
AB  - Square pyramidal o-semiquinonic nickel complexes with 2,6
      bis(diphenylphosphinomethyl)phenyl have a flexible coordination sphere and exist
      in solution as the mixture of tautomers rapidly, according to EPR time scale,
      interconverting at room temperature.

PMID- 14594306
TI  - Catalytic C=N bond metathesis of carbodiimides by group 4 and 5 imido complexes
      supported by guanidinate ligands.
AB  - A family of guanidinate-supported imido metal complexes are novel, effective
      catalysts for C=N metathesis of alkyl and aryl carbodiimides and evidence
      suggests that this reaction proceeds via a sequential addition/elimination
      pathway.

PMID- 14594307
TI  - Synthesis and reactivity of enediynyl amino acids and peptides: a novel concept
      in lowering the activation energy of Bergman cyclisation by H-bonding and
      electrostatic interactions.
AB  - Novel enediynyl amino acids and peptides 3 and 5-8 were synthesized and their
      thermal reactivity towards Bergman cyclization studied and compared with the
      earlier reported amino acid 4, which demonstrated, for the first time, the effect
      of H-bonding and electrostatic interactions in lowering the activation energy of
      Bergman cyclization.

PMID- 14594308
TI  - Stereochemical elucidation of the 1,4 polyketide amphidinoketide I.
AB  - The relative and absolute stereochemistry of amphidinoketide I has been
      determined by the total synthesis of all the diastereoisomers. Molecular
      modelling suggests that the natural product is not the thermodynamically
      preferred diastereoisomer.

PMID- 14594309
TI  - 2,6-Bis(styryl)anthracene derivatives with large two-photon cross-sections.
AB  - The first synthesis of 2,6-bis(styryl)anthrance derivatives with very large two
      photon cross sections is reported.

PMID- 14594310
TI  - Deep desulfurization by selective adsorption of dibenzothiophenes on Ag+/SBA-15
      and Ag+/SiO2.
AB  - Silver (Ag+) salts adsorbed on amorphous silica or mesoporous SBA-15 extract
      dibenzothiophene (DBT) and 4,6-dimethyldibenzothiophene (4,6-Me2DBT) from
      simulated, hydrotreated petroleum feedstocks.

PMID- 14594311
TI  - Palladium-catalyzed addition of organoboronic acids to allenes.
AB  - The palladium-catalyzed addition reaction of alkenyl- or aryl-boronic acids into
      various allenes is described, which allows C-C bond formation in a highly
      regioselective manner under very mild conditions.

PMID- 14594312
TI  - Catalytic asymmetric hydrogenation in a room temperature ionic liquid using
      chiral Rh-complex of ionic liquid grafted 1,4-bisphosphine ligand.
AB  - Introduction of imidazolium ionic liquid pattern to the catalyst not only avoided
      catalyst leaching but also increased the stability of catalyst in ionic liquid,
      and thus, the Rh-complex of 1,4-bisphosphine bearing two imidazolium salt
      moieties was successfully immobilized in an ionic liquid and reused several times
      for the hydrogenation of an enamide without significant loss of catalytic
      efficiency.

PMID- 14594313
TI  - Organically modified Pd-silica catalysts applied in Heck coupling.
AB  - Pd-silica catalysts prepared by depositing Pd onto silica precursors modified by
      surface methyl or phenyl groups through the reduction of Pd2+ ions with surface
      Si-H functions exhibit high activity and selectivity in Heck coupling.

PMID- 14594314
TI  - Syntheses and remarkable photophysical properties of 5-(2-pyridyl) pyrazolate
      boron complexes; photoinduced electron transfer.
AB  - A new series of pyridyl pyrazolate boron complexes 2a-e have been synthesized, in
      which 2a-c exhibit remarkable dual fluorescence properties due to the
      photoinduced electron transfer reaction.

PMID- 14594316
TI  - Readily synthesised arylamino fumaronitrile for non-doped red organic light
      emitting diodes.
AB  - Bright (maximum 10034 cd m(-2), 455 cd m(-2) at 20 mA cm(-2)) and efficient
      (maximum 2.4% at 4 mA cm(-2)) red (lambda(max)el 634-636 nm) organic light
      emitting diodes employ arylamino-substituted fumaronitrile as the novel host
      emitter, which is readily prepared and easily purified.

PMID- 14594315
TI  - Novel poly(amino ester)s obtained from Michael addition polymerizations of
      trifunctional amine monomers with diacrylates: safe and efficient DNA carriers.
AB  - Novel biodegradable poly(amino ester)s containing secondary and tertiary amines
      in the backbones were obtained from the Michael addition polymerizations of
      trifunctional amine monomers with diacrylates, and showed high transfection
      efficiency for the delivery of DNA comparable to those of polyethylenimine (PEI)
      and low cytotoxicity.

PMID- 14594317
TI  - Fabrication of SiC-C coaxial nanocables: thickness control of C outer layers.
AB  - Aligned SiC-C coaxial nanocables were synthesized via the direct growth of SiC
      nanowires from silicon substrates and subsequent carbon deposition using
      pyrolysis of methane; the average diameter of the SiC nanowire cores is 20 nm;
      the thickness of the C outer layers is controlled in the range 3-50 nm; the
      degree of crystalline perfection of the graphitic sheets increases with the
      thickness.

PMID- 14594318
TI  - Stereoinversion of beta- and gamma-substituted alpha-amino acids using a chemo
      enzymatic oxidation-reduction procedure.
AB  - Both D- and L-beta- and gamma-substituted alpha-amino acids can be interconverted
      to their respective L- and D- diastereoisomers by treatment with an
      enantioselective amino acid oxidase and a chemical reducing agent.

PMID- 14594319
TI  - Factors influencing analysis of prolyl endopeptidase in human blood and
      cerebrospinal fluid: increase in assay sensitivity.
AB  - Prolyl endopeptidase (EC 3.4.21.26) (PEP) is present in nearly all investigated
      mammalian cells and biological fluids and might be involved in the degradation of
      physiologically important neuropeptides. To be able to investigate the variation
      of PEP in blood and cerebrospinal fluid (CSF) in human disease, the factors
      influencing analysis of PEP in these body fluids must be determined. The purpose
      of the present work was to study the influence of storage conditions,
      anticoagulation additives, freezing and thawing and substrate solvent on
      determination of PEP in blood plasma/serum and CSF. It was found that the PEP
      activity was about 10% higher in plasma (with EDTA and heparinate for
      anticoagulation) than in serum. Storage at room temperature (20 degrees C) caused
      a rapid decline in enzyme activity, which was smaller but still considerable at 4
      degrees C. Storage at -20 degrees C and -70 degrees C did not decrease the PEP
      activity. Freezing and thawing of plasma/serum samples showed that the first
      freeze-thawing cycle produced a 20% reduction in enzyme activity but little
      further decrease was observed during subsequent cycles of freeze-thawing. In
      conclusion, PEP activity should preferably be measured within one hour after
      sampling using EDTA- or heparinate plasma. For long-term storage, samples should
      be immediately frozen and stored at -20 degrees C or colder. The selection and
      amount of the organic solvent used to dissolve the fluorogenic substrate strongly
      influenced the sensitivity of the assay. By developing an optimal solvent system
      an increase in assay sensitivity of about 400% could be obtained, which for the
      first time allowed measurement of the PEP activity in CSF.

PMID- 14594320
TI  - Clotting time by free oscillation rheometry and visual inspection and a
      viscoelastic description of the clotting phenomenon.
AB  - An automated procedure for determination of clotting time in whole blood was
      validated by direct comparison with the reference method, visual clotting time
      determination. The procedure was based on a 10 Hz free oscillation rheometer
      (FOR) of our design, the ReoRox 4. Recalcified citrated blood samples (n = 30),
      clotting in the range 4 to 20 min, were used in the validation. Every 30 s of the
      analysis, as the change in stiffness (deltaG*) of the sample was monitored by
      FOR, the sample cup was shortly removed from the FOR and its contents inspected
      for first signs of clotting, i.e. visual clotting time determination. Various FOR
      clotting criteria were attempted. Best correlation to visual clotting time was
      found when deltaG* reached 0.01 Pa, which yielded linear regression slope,
      intercept and r2 of 0.98, 0.09 min and 0.98, respectively. For comparison, six
      plasma samples were analyzed in the same way and gave almost the same results.
      The accuracy of the FOR determinations was checked by also analyzing, in
      parallel, portions of the sample with a conventional oscillation rheometer, a
      Bohlin VOR. The rationale is given for preferring deltaG* over G* as a FOR
      monitoring function in coagulation tests and for including median filtration of
      the primary FOR data. An extension of the FOR theory to include deltaG* and
      evidence in support of inhomogeneous blood clotting are also given.

PMID- 14594322
TI  - Deviations in coagulation activation due to treatment with different
      haemodialysis membranes.
AB  - Despite systemic heparinization, extracorporeal circulation will induce
      activation of blood coagulation. Thrombogenicity is associated with
      biocompatibility of dialysis membranes. Investigation of procoagulatory and
      fibrinolytic activity is performed prior to and during treatment with
      haemodialysis. In this study fluctuations of plasma coagulation factor XII,
      thrombin antithrombin complexes, prothrombin fragment 1 + 2 and thrombus
      precursor protein were monitored in 10 subjects during treatment with
      haemodialysis. Subjects were treated with both polysulphone high-flux dialyser
      membranes (F-60) and low-flux poly-methyl-methacrylate (PMMA) membranes.
      Immediately after start of treatment, blood in contact with artificial membrane
      surfaces resulted in a marked decrease in factor XII activity amounting to a mean
      reduction of 80% in the case of PMMA and a reduction of 40% in the case of F-60.
      In due course, a steady, on-going generation of thrombin antithrombin complexes
      was observed in several subjects, especially after treatment with F-60 membranes,
      amounting to increases exceeding 100% of initial values. Establishment of
      fibrinogen, prothrombin fragment 1 + 2 and thrombus precursor protein plasma
      concentrations yielded enhanced results for PMMA compared with the results for
      treatment with F-60 dialysis membranes. In order to prevent activation of
      clotting during several stages of haemodialysis, supplementation of anticoagulant
      can be established on the basis of analytical results of coagulation parameters.

PMID- 14594321
TI  - Total pregnancy-associated plasma protein A--a first trimester maternal serum
      marker for Down's syndrome: clinical and technical assessment of a poly
      monoclonal enzyme immunoassay.
AB  - Pregnancy-associated plasma protein A (PAPP-A) is a maternal serum marker of
      fetal chromosomal disease and a risk marker for adverse outcome. PAPP-A in the
      circulation exists both as a 2:2 complex (PAPP-A/proMBP) with the proform of
      eosinophil major basic protein (proMBP) and as dimeric PAPP-A. Non-PAPP-A
      containing proMBP complexes constitute the bulk of proMBP in maternal serum. We
      developed and characterized a sandwich enzyme immunoassay for PAPP-A using a
      polyclonal rabbit anti-PAPP-A/proMBP antibody (SSI 6823) and a monoclonal murine
      anti-PAPP-A/proMBP antibody (HYB 234-3), reactive with the PAPP-A part of PAPP
      A/proMBP. The assay range was 2 mIU/L-500 mIU/L, intra- and inter-assay
      coefficients of variation <10%. The immunoreactivity eluted ahead of
      thyroglobulin, Mr 669 kDa, in gel filtration and bound to a heparin column. Serum
      concentrations of PAPP-A were determined in gestational weeks 5-13 in 167
      pregnant women with normal fetuses and 39 women with Down's syndrome (DS)
      fetuses. The median PAPP-A MoM (multiples of the median in normal controls) in DS
      pregnancies was 0.30 (quartile range: 0.17-0.54). The PAPP-A logMoMs in DS
      pregnancies were normally distributed with a mean of -0.5927 and SD of 0.3639.
      When simulating the performance of PAPP-A and age as markers for DS in population
      screening a detection rate (DR) of 62% was found for a screen positive rate (SPR)
      of 5%. Together with beta-HCG and nuchal translucency, two other first trimester
      markers for fetal DS, a DR 90% could be obtained for an SPR of 5%.

PMID- 14594323
TI  - Kallikrein modification with affinity to IgG present in higher amounts than
      normal in plasma from patients with Crohn's disease.
AB  - This study presents immunological and functional evidence to suggest that the
      activation of prekallikrein (PK) in human plasma yields two modifications of
      kallikrein. One of these modifications showed amidolytic properties strongly
      deviating from those registered for the main part of the enzyme. The substrates
      were S-2302, Bz-Pro-Phe-Arg-pNA, S-2366 and S-2222. In PAGE immunoblots the PK
      heavy chain mAb 13G11 was found to detect the kallikrein 85 kD double band and
      bands with mol. weights of about 152 and 135 kD. Such a 152 kD band could be
      removed together with an IgG fraction on a Protein G column. In this study the
      kallikrein identity was confirmed by an estimation of the levels obtained in
      amidolytic assays of mixtures of normal plasma and plasma deficient in FXI, which
      in immunological assays showed a PK level of 140-150%, of normal. A comparison in
      amidolytic assays of normal plasma and plasma from patients with Crohn's disease
      showed that patients' plasma contained a significantly higher level than normal
      of modified kallikrein. An IgG removal procedure removed all modified kallikrein,
      and did not affect ordinary kallikrein levels.

PMID- 14594324
TI  - Measurement of glucose content in plasma from capillary blood in diagnosis of
      diabetes mellitus.
AB  - Overall, there is good correlation between glucose values obtained from ear
      capillary blood and those from peripheral venous plasma, but there are
      considerable individual differences. Results obtained with these two methods are
      generally not interchangeable and the converted values should not be used in the
      diagnosis of diabetes mellitus, because of the risk of misclassification. In
      Denmark this can affect 20-24000 persons. The aim of our study was to investigate
      whether these differences might be less significant if measurements were taken at
      the plasma phase of capillary blood and expressed directly as capillary plasma
      results and if finger capillary blood were used instead of ear capillary blood.
      The Hitachi 717 instrument was used for measurements of glucose concentrations in
      venous plasma, the Cobas Mira S in capillary whole blood and the Accu-Chek Inform
      from Roche in capillary plasma. The conclusions drawn were (1) capillary ear
      blood glucose concentration correlates well with capillary finger blood
      concentration and the two sites can be used interchangeably, yielding similar
      results in the individual patient; (2) sampling variation is almost the same
      (approx. 0.16 mmol/L) on capillary plasma and capillary whole blood from finger
      and ear. Sampling variation for venous plasma measured on the Hitachi instrument
      was 0.13 mmol/L; not significantly better; (3) the analytical imprecision of
      glucose measurements on capillary plasma (Accu-Chek Inform) and capillary whole
      blood (haemolysate method) is almost the same (approx. 2.0%). The analytical
      imprecision of glucose measurements on venous plasma is 0.9% using a laboratory
      method and almost twice as high using Accu-Chek Inform (2.1%); (4) determination
      of capillary plasma values in the finger did not improve the correlation with
      venous plasma values. Even though average values were in better concordance,
      individual differences did not change. For some persons, both ear- and finger
      capillary blood measurements deviate significantly from results on venous plasma,
      such that they cannot be used for diagnosis of diabetes mellitus; (5) the main
      factor for good correlation is the sampling site. Results obtained on plasma and
      whole blood from the same puncture correlate well; (6) neither capillary blood
      nor capillary plasma correlates with the venous plasma method recommended by the
      American Diabetes Association. It is concluded that physiologic differences in
      glucose content in capillary- and venous blood prohibit the random use of these
      two materials in the diagnosis of diabetes.

PMID- 14594325
TI  - Subjects with a shortened activated partial thromboplastin time show increased in
      hospital mortality associated with elevated D-dimer, C-reactive protein and
      glucose levels.
AB  - BACKGROUND: Shortened activated partial thromboplastin time (aPTT) values are
      associated with enhanced coagulation activation. However, the clinical relevance
      of shortened aPTTs is not well defined. The aim of this study was to determine
      the in-hospital mortality rate in subjects with shortened aPTTs and the effects
      of polymorphism in plasminogen activator inhibitor (PAI)-, t-PA- and factor XIII
      gene on the coagulation status. D-dimer, C-reactive protein (CRP) and glucose,
      markers that have been related with increased mortality, were tested. RESULTS: We
      found that a shortened aPTT on admission was associated with an increased risk of
      in-hospital mortality (OR=2.6, 95% CI: 2.1-3.5). Non-survivors with short aPTTs
      had significantly higher plasma D-dimer, CRP and glucose levels compared with
      survivors. Subjects homozygous for PAI-1 5G and t-PA I alleles showed higher
      plasma D-dimer levels compared with 4G/4G PAI-1 (p=0.02) and D/D t-PA (p=0.001)
      homozygotes, respectively. CONCLUSIONS: These results suggest that PAI-1 4G/5G
      and t-PA I/D polymorphisms determine plasma D-dimer levels in patients with
      shortened aPTT values. Preliminary results show that, among patients with short
      aPTTs, homozygosity for the hyperfibrinolytic PAI-1 5G or tPA I alleles are at
      increased risk of in-hospital mortality compared with 4G/4G PAI-1 and D/D tPA
      homozygotes (OR=2.6, 95% CI: 1.3-5.5 and OR=5.5, 95% CI: 1.3-24.5, respectively).

PMID- 14594326
TI  - Preanalytical handling of samples for measurement of plasma lactate in HIV
      patients.
AB  - Lactic acidosis is a feared side effect of nucleoside analog treatment, one of
      the cornerstones in the management of HIV infection. Precise and reliable lactate
      measurements are prerequisites for the diagnosis of hyperlactatemia. The effects
      of venous stasis, time to measurement and storage temperature on p-lactate
      levels, p-glucose levels, anion gap and pH were investigated. Ten HIV patients
      (n=8 on highly active antiretroviral therapy) and 4 healthy control subjects were
      studied. Blood was drawn without stasis at time 0 and with stasis for 2 and 8 min
      into heparin-preserved test tubes. The tubes were placed at a room temperature
      (25 degrees C) and on crushed ice and consecutively monitored for up to 360 min.
      The mean increases in p-lactate in blood kept in test tubes at 25 degrees C,
      measured from 0 to 60 min and from 240 to 360 min, were increased in HIV patients
      compared with controls (0.78 mmol/Lh +/- 0.02 vs. 0.63 mmol/Lh +/- 0.05,
      (p=0.009) and 0.65 mmol/Lh +/- 0.03 vs. 0.53 mmol/Lh +/- 0.05, (p=0.042)). It was
      found that placing the tubes on crushed ice rather than keeping them at 25
      degrees C controlled glycolysis and lactate production measured over a 6-h period
      (0.033 mmol/Lh +/- 0.006 vs. 0.32 mmol/Lh +/- 0.01, (p<0.0001) and 0.064 mmol/Lh
      +/- 0.008 vs. 0.64 mmol/Lh +/- 0.02, (p<0.0001)). The total increases in lactate
      levels in the test tubes placed on crushed ice for 4 h and in those kept at 25
      degrees C for 15 min were comparable (0.28 +/- 0.03 mmol/L vs. 0.20 +/- 0.03).
      Compared with storage at 25 degrees C, keeping the test tubes on crushed ice also
      preserved pH and anion gap over a 6-h measurement period (pH: 0.026 +/- 0.004 vs.
      0.12 +/- 0.01 and anion gap: -0.8 +/- 0.4 mmol/L vs. 4.1 +/- 0.4). Two minutes of
      venous stasis had no influence on p-lactate levels (0.02 +/- 0.04 mmol/L,
      p=0.70), whereas 8 min of stasis increased p-lactate levels by 0.11 +/- 0.04
      mmol/L, p=0.009. It is concluded that major errors in measurements of p-lactate,
      anion gap and pH can be prevented by placing test tubes on crushed ice for up to
      4 h until measurement.

PMID- 14594327
TI  - The Quick and Owren prothrombin time methods for oral anticoagulant therapy do
      not agree well using the International Normalized Ratio (INR) units.

PMID- 14594328
TI  - Theory of Mind--based action in children from the autism spectrum.
AB  - In this study we investigated whether task interest facilitated the application
      of Theory of Mind capacities in high-functioning children from the autism
      spectrum. Children were invited to carry out two simple tasks. Sabotage of both
      tasks by a third party resulted in the experimenter appearing to have a false
      belief. Whereas pervasive developmental disorder not otherwise specified (PDDNOS)
      children tended to correct the experimenter's false belief in the rewarded task
      condition, children with autism were not influenced by task condition. These
      results highlight the role played by social and communicative factors in the
      application of Theory of Mind knowledge in the former clinical group.

PMID- 14594329
TI  - Peer interaction and loneliness in high-functioning children with autism.
AB  - Social interaction with peers and the understanding and feelings of loneliness
      were examined in 18 high-functioning children with autism and 17 typically
      developing children matched for IQ, chronological age, gender, and maternal
      education. Observations were conducted on children's spontaneous social
      initiations and responses to their peers in natural settings such as recess and
      snack time, and children reported on their understanding and feelings of
      loneliness and social interaction. Overall, children with autism revealed a good
      understanding of both social interaction and loneliness, and they demonstrated a
      high level of social initiation. However, they spent only half the time in social
      interactions with peers compared with their matched counterparts, and they
      interacted more often with a typically developing child than with another special
      education child. Despite the intergroup differences in frequency of interaction,
      a similar distribution of interactions emerged for both groups, who presented
      mostly positive social behaviors, fewer low-level behaviors, and very infrequent
      negative behaviors. Children with autism reported higher degrees of loneliness
      than their typical age-mates, as well as a lower association between social
      interaction and loneliness, suggesting their poorer understanding of the
      relations between loneliness and social interaction. Research and practice
      implications of these findings are discussed.

PMID- 14594330
TI  - The Friendship Questionnaire: an investigation of adults with Asperger syndrome
      or high-functioning autism, and normal sex differences.
AB  - Friendship is an important part of normal social functioning, yet there are
      precious few instruments for measuring individual differences in this domain. In
      this article, we report a new self-report questionnaire, the Friendship
      Questionnaire (FQ), for use with adults of normal intelligence. A high score on
      the FQ is achieved by the respondent reporting that they enjoy close, empathic,
      supportive, caring friendships that are important to them; that they like and are
      interested in people; and that they enjoy interacting with others for its own
      sake. The FQ has a maximum score of 135 and a minimum of zero. In Study 1, we
      carried out a study of n = 76 (27 males and 49 females) adults from a general
      population, to test for previously reported sex differences in friendships. This
      confirmed that women scored significantly higher than men. In Study 2, we
      employed the FQ with n = 68 adults (51 males, 17 females) with Asperger Syndrome
      or high-functioning autism to test the theory that autism is an extreme form of
      the male brain. The adults with Asperger Syndrome or high-functioning autism
      scored significantly lower on the FQ than both the male and female controls from
      Study 1. The FQ thus reveals both a sex difference in the style of friendship in
      the general population, and provides support for the extreme male brain theory of
      autism.

PMID- 14594331
TI  - Sequential evaluation of reinforced compliance and graduated request delivery for
      the treatment of noncompliance in children with developmental disabilities.
AB  - Errorless compliance training is a recently developed approach that has been
      demonstrated to be effective in treating severe oppositional behavior in
      children. In conjunction with several ancillary techniques, the approach
      comprises two fundamental components: reinforcement for child compliance and
      delivery of requests in a four-level hierarchy, from requests that yield high
      levels of compliance to those that yield low levels. To determine the relative
      contribution of each component, four children with developmental disabilities and
      severe oppositional behavior were observationally assessed in baseline and then
      treated using reinforcement following each instance of compliance to parental
      requests. Following this first treatment phase, we used the graduated request
      hierarchy in conjunction with reinforced compliance. Results indicated that use
      of reinforcement for compliance in isolation was ineffective in bringing about
      clinically significant improvements in child compliance. The addition of the
      graduated request hierarchy appeared to be associated with substantial changes in
      child compliance that maintained in follow-up assessments.

PMID- 14594332
TI  - Prevalence and patterns of use of psychoactive medicines among individuals with
      autism in the Autism Society of Ohio.
AB  - To date, there have been few surveys of psychotropic and antiepileptic drug (AED)
      prevalence in individuals with autism-spectrum conditions. We surveyed 747
      families in the Autism Society of Ohio regarding the use of psychotropic drugs,
      AEDs, and over-the-counter (OTC) preparations for autism. In all, 417 families
      (55.8%) replied. A total of 45.6% were taking some form of psychotropic agent
      (including St. John's wort and melatonin), whereas 11.5% were taking AEDs, and
      10.3% took OTC autism preparations. The most common psychotropic agents included
      antidepressants (21.6%), antipsychotics (14.9%), antihypertensives (12.5%), and
      stimulants (11.3%). Some 51.6% were prescribed psychotropic drugs or AEDs, and
      55.4% took psychotropic drugs, AEDs, or autism supplements. Demographic variables
      frequently found to be associated with medication use included greater age, more
      severe autism, more severe intellectual handicap, and housing outside the family
      home. Whereas there is empirical support for the use of some of these
      psychotropic agents in autism, others are being prescribed with minimal research
      support. OTC autism preparations were used in substantial numbers of individuals,
      despite limited research support and the possibility of toxic effects.

PMID- 14594333
TI  - The effect of choice-making opportunities during activity schedules on task
      engagement of adults with autism.
AB  - Increasing choice and participation by adults with autism spectrum disorders is
      an important, but neglected, aspect of research and services. This study
      evaluated the effects of choice-making opportunities, embedded within activity
      schedules, and contingent praise on the engagement of three adults with autism in
      a community vocational setting. In the baseline condition, staff assigned the
      order of the tasks. In the Choice condition and Maintenance phases, the
      participants chose the order of tasks that supervisors assigned to them. They
      made their own activity schedules by writing down the order of their tasks for
      that morning. Social praise was provided contingent on the participant's task
      completion. The same tasks were used in baseline, intervention, and maintenance
      phases. During the Choice and Maintenance conditions, client engagement was
      substantially higher than baseline for all three participants. Increasing choice
      making opportunities within activity schedules was an effective and socially
      acceptable way to increase choice and engagement in adults with autism.

PMID- 14594334
TI  - Abnormal brain lateralization in high-functioning autism.
AB  - Disturbances in lateral preference in autism are of interest because of their
      potential to shed light on brain maturational processes in this disorder. Forty
      seven autistic individuals with a history of disordered early language
      development and 22 autistic individuals with normal early language acquisition
      were matched with 112 healthy individuals and compared on a standardized measure
      of lateral preference, the Edinburgh Handedness Inventory. Autistic individuals
      with a history of early language disturbance showed more atypical cerebral
      dominance than both healthy participants and autistic individuals with normal
      early language skills. The data indicated maturational disturbances in
      establishing lateral preference rather than increased rates of left handedness.
      Atypical establishment of cerebral dominance may be one cause of disordered
      language development in autism.

PMID- 14594335
TI  - The understanding of actions and intentions in autism.

PMID- 14594336
TI  - Response to Goldstein's commentary: Interventions to facilitate auditory, visual,
      and motor integration: "show me the data".

PMID- 14594337
TI  - Re: Autism--ear infections--glue ear--sleep disorders.

PMID- 14594338
TI  - Neonatal tuberculous meningitis in a patient with Asperger's syndrome.

PMID- 14594339
TI  - The diabetes epidemic: can we stop the spread?

PMID- 14594340
TI  - Clinical and microbiologic analysis of a hospital's extended-spectrum beta
      lactamase-producing isolates over a 2-year period.
AB  - STUDY OBJECTIVE: To evaluate the microbiologic and clinical outcomes of patients
      with extended-spectrum beta-lactamase (ESBL)-producing isolates over a 2-year
      period. DESIGN: Retrospective analysis. SETTING: Tertiary care teaching hospital.
      PATIENTS: Twenty-one patients with cultures of confirmed ESBL-producing
      Escherichia coli, Klebsiella pneumoniae, or Klebsiella oxytoca. MEASUREMENTS AND
      MAIN RESULTS: Antimicrobial susceptibilities of piperacillin-tazobactam,
      cefotetan, carbapenems, aminoglycosides, fluoroquinolones, trimethoprim
      sulfamethoxazole, and nitrofurantoin (nitrofurantoin for urinary isolates only)
      of confirmed ESBL producers at our institution were determined, as well as
      clinical outcomes of patients with ESBL-producing isolates. Microbiologic and
      medical records were reviewed for patient sex and age, antimicrobial
      susceptibilities, antimicrobial therapy, and clinical and microbiologic outcomes.
      From January 2000-December 2001, 31 isolates were confirmed as ESBL producers (6
      E. coli, 11 K. pneumoniae, and 14 K. oxytoca). A statistically significant
      increase occurred over the 2-year period from 9 (0.6%) of 1414 isolates in 2000
      to 22 (1.8%) of 1218 isolates in 2001 (p = 0.0055). All isolates were susceptible
      to carbapenems, and more than 88% were susceptible to amikacin, cefotetan, or
      nitrofurantoin. Less than 70% of isolates were susceptible to gentamicin,
      fluoroquinolones, piperacillin-tazobactam, or trimethoprim-sulfamethoxazole. All
      patients treated with a carbapenem experienced clinical cure. Piperacillin
      tazobactam alone and in combination resulted in an overall clinical cure rate of
      55%, with a 50% cure rate for isolates susceptible to piperacillin-tazobactam.
      All patients in whom antibiotic therapy failed had been treated with piperacillin
      tazobactam or cefepime, either alone or in combination with a fluoroquinolone.
      CONCLUSION: Carbapenems remain the treatment of choice for ESBL-producing
      pathogens. Piperacillin-tazobactam and cefepime should not be routinely
      administered for the treatment of these organisms.

PMID- 14594341
TI  - Putting an Ecstasy test kit to the test: harm reduction or harm induction?
AB  - OBJECTIVE: To evaluate the DanceSafe Complete Adulterant Screening Kit for
      Ecstasy with regard to its accuracy in identifying 3,4-methylenedioxymeth
      amphetamine (MDMA) and methylenedioxyamphetamine (MDA) derivatives and its
      ability to detect certain contaminants. METHODS: In part 1, 39 street-grade
      tablets purported to be MDMA were tested with the Marquis, Mecke, and Simon's
      reagents provided by the DanceSafe testing kit. The tablets then were submitted
      to gas chromatography-mass spectrometry for identification of active ingredients.
      In part II, seven known drugs of abuse were tested with the Marquis, Mecke, and
      Simon's reagents. These drugs were codeine, dextromethorphan, dihydrocodeine,
      ketamine, MDMA, morphine, and d-norpropoxyphene. RESULTS: The Marquis, Mecke, and
      Simon's reagents did not differentiate pure MDMA from adulterated forms. They
      lacked both sensitivity and specificity for the purpose of MDMA identification
      when tested by persons unfamiliar with these reagents. Also, experienced
      toxicologists using this unfamiliar procedure generated false-positive results.
      CONCLUSIONS: Neither the Marquis, Mecke, nor Simon's reagents should be used by
      the public for harm reduction purposes. These agents do not help identify pure
      MDMA tablets. Gas chromatography-mass spectrometry remains the most sensitive and
      specific testing method for identifying MDMA and its contaminants.

PMID- 14594342
TI  - A retrospective evaluation of vitamin K1 therapy to reverse the anticoagulant
      effect of warfarin.
AB  - STUDY OBJECTIVE: To assess compliance with the 2001 consensus guidelines of the
      American College of Chest Physicians (ACCP) regarding administration of vitamin
      K1 to reverse the anticoagulant effect of warfarin. DESIGN: Retrospective chart
      review. SETTING: University teaching hospital. PATIENTS: Fifty-five adult
      inpatients who received both warfarin and vitamin K1 between September 2001 and
      January 2002. MEASUREMENTS AND MAIN RESULTS: The patients' medical records were
      evaluated; data were collected on patient demographics and on vitamin K1 dosage
      and route of administration, warfarin dosage, and international normalized ratio
      (INR) before and after vitamin K1 administration. Administration routes and 87
      doses of vitamin K1 prescribed for the 55 patients were assessed for compliance
      with the ACCP guidelines. Administration routes were subcutaneous (40.2% of
      doses), intravenous (35.6%), oral (13.8%), and intramuscular (10.3%). The most
      frequently prescribed dose of vitamin K1 was 10 mg (32.2%), followed by 2 mg
      (21.8%) and 5 mg (18.4%). Rates of compliance with the ACCP guidelines
      categorized by INR value were as follows: INR below 5, 12.2%; INR 5-9, 27.8%; INR
      between 9 and 20, 26.7%; and INR above 20, 0%. Four patients had documented
      episodes of bleeding and received seven doses of vitamin K1. Twenty-six patients
      received fresh frozen plasma with vitamin K1. Overall compliance with ACCP
      recommended doses and routes of vitamin K1 was only 17.2%. CONCLUSION: The most
      frequently prescribed administration routes for vitamin K1 were subcutaneous and
      intravenous, indicating that the oral route is often not used as recommended. The
      vitamin K1 doses prescribed for reversal of warfarin anticoagulation were highly
      variable, and for most (83%) patients, the recommended guidelines were not
      followed. The clinical significance of noncompliance with the ACCP guidelines for
      vitamin K1 administration warrants further study.

PMID- 14594344
TI  - Pharmacokinetic study in women of three different doses of a new formulation of
      oral testosterone undecanoate, Andriol Testocaps.
AB  - STUDY OBJECTIVE: To assess the pharmacokinetic parameters of testosterone
      undecanoate after administration of a new oral formulation, Andriol Testocaps.
      DESIGN: Randomized, open-label, group-comparative, parallel-design, dose
      proportionality study. SETTING: Clinical pharmacology unit. SUBJECTS: Forty-five
      healthy women without childbearing potential. INTERVENTION: Two oral doses each
      of testosterone undecanoate 20, 40, or 80 mg were administered with meals,
      separated by a 12-hour dosing interval. MEASUREMENTS AND MAIN RESULTS: Serum
      concentrations of testosterone undecanoate were assayed by liquid chromatography
      with mass spectrometric detection, and of testosterone and 5alpha
      dihydrotestosterone (DHT) by gas chromatography with mass spectrometric
      detection. Pharmacokinetic parameters were calculated using standard methods.
      Statistical analysis of dose proportionality was performed on the log(e)
      transforms of dose-normalized area under the serum concentration-time curve from
      0-12 hours (AUC(0-12)) and from zero to the sampling time of the last measurable
      concentration after administration of the second dose (AUC(0-t(last)), and
      maximum serum concentration after the first dose (C(max)l). For testosterone
      undecanoate, testosterone, and DHT, dose-related increases in plasma
      concentrations were found with increasing doses of testosterone undecanoate;
      maximum concentrations were found 5-7 hours after administration. Using baseline
      corrected testosterone values, dose proportionality for testosterone was found
      for AUC(0-12), AUC(0-t)(last), and C(max)(l). After higher doses, plasma levels
      of testosterone undecanoate were higher and plasma levels of DHT lower than could
      be expected assuming dose proportionality. CONCLUSION: Serum testosterone levels
      are dose proportional after oral administration of two doses of a new formulation
      of testosterone undecanoate 20, 40, and 80 mg, Andriol Testocaps.

PMID- 14594343
TI  - Comorbidities and associated treatment charges in patients with anxiety
      disorders.
AB  - OBJECTIVE: To describe comorbidities and treatment charges in patients receiving
      initial anxiolytic therapy for anxiety disorders. DESIGN: Retrospective data
      analysis. PATIENTS: Six thousand six hundred forty-seven patients with anxiety
      disorders. MEASUREMENTS AND MAIN RESULTS: Analysis was conducted using medical
      and pharmacy data for patients in 26 United States health plans from the
      PharMetrics Integrated Outcomes database. Data were collected for 12 months
      before and after the first anxiolytic prescription date (index date) during the
      study period (January 1, 1998-December 31, 2000). The sample comprised patients
      with a diagnosis of anxiety disorder whose original anxiolytic prescription had
      been refilled within 120 days. International Classification of Diseases, 9th
      revision, Clinical Modification (ICD-9-CM) codes and medical and prescription
      data identified the existence of comorbidities, and medical and prescription
      charges. The most common diagnoses of anxiety disorder were anxiety not otherwise
      specified (67%), panic disorder (14%), and generalized anxiety disorder (13%).
      The most commonly prescribed anxiolytics were benzodiazepines, such as alprazolam
      (43%) and lorazepam (27%). Hypertension was the most common nonpsychiatric
      comorbidity (22%) and depression the most common psychiatric comorbidity (37%).
      Other comorbidities observed were lipid disorders (17%), chronic obstructive
      pulmonary disease (9%), and asthma (7%). Total treatment charges 12 months before
      and after initial anxiety diagnosis and anxiolytic prescription were dollar 6279
      and dollar 9270, respectively (p < 0.0001). CONCLUSION: Chronic conditions are
      commonly associated with anxiety disorders. Recognizing these psychiatric and
      nonpsychiatric comorbidities is important when treating patients with these
      disorders. Treatment charges are significantly higher when a patient is diagnosed
      with an anxiety disorder, highlighting the impact of anxiety on the total cost of
      treatment for these patients.

PMID- 14594345
TI  - The evolving role of nesiritide in advanced or decompensated heart failure.
AB  - Nesiritide is a recombinant form of human brain natriuretic peptide (BNP) that is
      structurally and biochemically identical to endogenously produced BNP. In humans,
      BNP is important in hemodynamic and neurohormonal equilibrium, helping to
      maintain adequate vascular volume and pressure in response to volume overload.
      The pharmacodynamic effects of nesiritide mimic the biologic effects of BNP. The
      molecular biology and actions of nesiritide and BNP are reviewed, with the
      therapeutic rationale for nesiritide in patients with acute or advanced
      decompensated heart failure highlighted. In addition, recommendations for its
      administration are provided, and unresolved therapeutic considerations are
      discussed.

PMID- 14594346
TI  - Advances in the pharmacotherapy of attention-deficit-hyperactivity disorder:
      focus on methylphenidate formulations.
AB  - The psychostimulant dl-methylphenidate (MPH) remains the most common drug therapy
      in child and adolescent psychiatry for the treatment of attention-deficit
      hyperactivity disorder (ADHD). Evidence of a dopaminergic basis both for the
      actions of MPH and for the underlying neuropathology in ADHD continues to mount.
      Advances in the biopharmaceutics of MPH have been conspicuous. Novel approaches
      to formulation design have resulted in new MPH delivery options to overcome the
      short-term actions of both immediate-and sustained-release MPH. New modified
      release MPH products offer the convenience of once-daily administration while
      providing extended absorption profiles that better mimic those of standard
      schedules of immediate-release MPH (i.e., the absorption phase of MPH better
      correlates with improved behavioral response than does the elimination phase).
      The oral bioavailability of MPH in females may be lower than in males. The l-MPH
      isomer exhibits only negligible oral bioavailability and, further, possesses
      little intrinsic activity at the dopamine transporter. This notwithstanding, a
      single-isomer d-MPH immediate-release product is now available for dosing
      recommended at one-half that of dl-MPH.

PMID- 14594347
TI  - Pharmacologic treatment of chronic obstructive pulmonary disease: past, present,
      and future.
AB  - Pharmacologic treatment of chronic obstructive pulmonary disease (COPD) has
      evolved considerably during the past several decades. Initial treatment of the
      disease was accomplished primarily through antibiotics, mucolytic agents, and
      nonselective sympathomimetic agents. Up-to-date treatment guidelines stratified
      according to strength of evidence are published in the National Heart, Lung, and
      Blood Institute-World Health Organization workshop report on the Global Strategy
      for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary
      Disease. Current drug therapy for stable COPD focuses primarily on
      bronchodilation through inhaled beta2-agonists and anticholinergic agents,
      immunization, and elimination of smoking as a risk factor. Although many
      pharmacologic agents are available to treat COPD, no drug has demonstrated
      effectiveness in halting progression of the disease. Rather, the goal of drug
      therapy at this time is to maintain control of symptoms and prevent COPD
      exacerbations. Compared with asthma, research into treatment for COPD has been
      minimal. However, a long-acting anticholinergic agent, tiotropium, has received
      approval status by the United States Food and Drug Administration. The drug has
      been shown to improve spirometric parameters, quality of life, and utilization of
      health care resources. In addition, several new targets for the treatment of COPD
      are being studied, and a few agents, including some that theoretically may slow
      functional decline in patients with COPD, are in development.

PMID- 14594348
TI  - New antiarrhythmic agents for atrial fibrillation and atrial flutter: United
      States drug market response as an indicator of acceptance.
AB  - OBJECTIVE: To determine how well dofetilide and Betapace AF (sotalol, approved
      solely for atrial fibrillation and atrial flutter), with their detailed dosing
      and monitoring guidelines for safety, were accepted into clinical practice during
      the 2 calendar years after their introduction. METHODS AND RESULTS: We reviewed
      the number of new, refill, and total prescriptions of all antiarrhythmic agents
      in the United States from April 2000-December 2001 to assess use of dofetilide
      and Betapace AF in the drug market. Both were prescribed very infrequently
      throughout the study period. In addition, the infrequent reported use of these
      drugs for patients with atrial fibrillation and flutter indicated poor acceptance
      of these agents by prescribing physicians. We speculated that the restricted
      distribution and required educational program for dofetilide, as well as the
      availability of generic sotalol products, may have discouraged physicians from
      prescribing both dofetilide and Betapace AE CONCLUSION: A common goal for both
      the dofetilide risk-management program and the creation of a sotalol product
      indicated solely for atrial fibrillation and atrial flutter was to provide safer
      treatment for patients with these arrhythmias. Unfortunately, limited penetration
      of dofetilide and Betapace AF into the U.S. market suggests that drugs without a
      risk-management program or detailed dosing guidelines were more likely than
      dofetilide or Betapace AF to be selected for treatment of atrial fibrillation and
      atrial flutter.

PMID- 14594349
TI  - Peritoneal dialysis fluid concentrations of linezolid in the treatment of
      vancomycin-resistant Enterococcus faecium peritonitis.
AB  - OBJECTIVE: To determine linezolid concentrations in peritoneal dialysis fluid
      after multiple oral doses of the drug in a 46-year-old man with vancomycin
      resistant Enterococcus faecium peritonitis who was undergoing peritoneal
      dialysis. METHODS: After administration of oral linezolid 600 mg twice/day was
      started, peritoneal dialysis fluid was collected at the end of several 4- and 8
      hour dwell times and submitted for analysis of linezolid concentration. Before
      linezolid therapy was begun, and immediately after several peritoneal dialysis
      exchanges, 30 ml of expended peritoneal dialysis fluid was collected in a sterile
      container and immediately frozen at -70 degrees C until analysis by high
      performance liquid chromatography. RESULTS: Peritoneal dialysis concentrations of
      linezolid greater than 4 microg/ml were achieved after the first dose of
      linezolid and maintained after repeated doses. During the course of therapy, mean
      linezolid concentrations in peritoneal dialysis fluid tended to increase (mean
      7.60 pg/ml, range 3.54-16.2 microg/ml). All assayed peritoneal dialysis samples
      demonstrated linezolid concentrations greater than 4 microg/ml at the end of 4-
      or 8-hour dwell times, except for one level after a missed dose on linezolid
      treatment day 3. Duration of dwell times did not appear to correlate with
      linezolid concentrations. CONCLUSION: In this patient, linezolid 600 mg twice/day
      penetrated into peritoneal dialysis fluid at or above the concentrations
      necessary to treat common gram-positive bacteria. Linezolid therapy is likely to
      have a role in peritoneal dialysis-associated peritonitis based on its
      antimicrobial activity, pharmacokinetic properties, ease of administration, and
      tolerability.

PMID- 14594350
TI  - Expression of LRP--lung resistance-related protein in the normal colorectal
      mucosa and in colorectal carcinoma.
AB  - Expression of LRP--lung resistance-related protein was analyzed by
      immunohistochemical staining with monoclonal antibody LRP-56 in 30 specimens (10
      from normal colorectal tissue and 20 from colorectal carcinoma). All normal
      tissue samples were LRP positive. Strong LRP staining was seen in the surface
      epithelium and upper parts of the crypts. Similarly, colorectal carcinomas
      demonstrated strong staining for LRP/MVP. Staining pattern of cytoplasm of
      carcinoma cells was the same as in the normal mucosa. The overexpression of LRP
      in the colorectal carcinoma may play a role in the process of carcinogenesis or
      be a marker of an aggressive phenotype. It seems, the high value of LRP is a
      predictor of response to chemotherapy and prognoses in various tumor types. (Fig.
      7, Ref: 18.).

PMID- 14594351
TI  - Olfactory activity in the human brain identified by fMRI.
AB  - BACKGROUND: Modern imaging methods such as functional magnetic resonance imaging
      (fMRI) or positron emission tomography (PET) enable us to map brain activities
      associated with stimulation of various functional systems in the human brain.
      Data concerning the localization and lateralization of secondary olfactory areas
      are not in agreement. SUBJECTIVE:  THE AIM OF THE STUDY: localization of
      secondary olfactory brain areas activated by a pleasant stimulus--vanillin.
      METHODS AND MATERIAL: Our fMRI method was based on the blood-oxygen-level
      dependent effect. All measurements were carried out on a 1.5 T scanner (Siemens
      Vision), using gradient-echo EPI technic. The basic block-like scheme included no
      odour/and odour was repeated 8 times. In the definitive phase of the study,
      experiments were performed on 12 healthy volunteers aged from 20 to 68 (9 men and
      3 women) stimulated birhinally by vanillin odour. RESULTS: Bilateral activations
      of the inferior frontal gyrus, anterior insular-periinsular area, hippocampus,
      amygdala, caudate nucleus and cerebellum were seen. A greater extent of
      activation was evident in the right hemisphere and in the right half of the
      cerebellum. CONCLUSIONS: The anterior insular-periinsular area and hippocampus
      can be considered as secondary olfactory areas in human brain. Strong activation
      of the right inferior frontal gyrus demonstrated in our study may be related to
      effort to name the presented odour. Activation of the cerebellum may be evaluated
      as a consequent phenomenon due to extensive activation of the frontal lobe.

PMID- 14594352
TI  - The significance of complement fixation test in clinical diagnosis of
      toxoplasmosis.
AB  - BACKGROUND: The complement fixation test (CFT) is the basic method in the
      diagnosis of toxoplasmosis. Despite its standard and reproducible results, it is
      rarely used in routine diagnosis of toxoplasmosis where the detection of IgG by
      means of EIA tests is widely used. OBJECTIVE: The study is focused on the
      verification of CFT value within the spectrum of specific classes of
      immunoglobulins IgG, IgM, IgA antibodies and avidity of IgG antibodies, as well
      as on the clinical diagnosis of toxoplasmosis. METHOD: The study analysed 1705
      samples of serum from patients suspected to be infected by Toxoplasma gondii. Out
      of these patients 451 suffered from acute lymphadenopathic toxoplasmosis (6 with
      seroconversion of both CFT and IgG antibodies) and 1254 serum samples were
      collected from patients with latent infection, out of whom 176 were with long
      term persistence of IgM, or IgA antibodies after the elimination of disease.
      CONCLUSION: CFT is a reliable indicator of Toxoplasma infection and as opposed to
      IgG antibodies its levels enable a more objective determination of its course.
      However from the aspect of the determination of the stage of toxoplasmosis from a
      single sample of serum, the combination of CFT with IgM or IgA antibodies with
      quantitative order or test of avidity of IgG antibodies must be performed. (Tab.
      4, Fig. 4, Ref. 30.).

PMID- 14594353
TI  - Relationship between plasma aldosterone and left ventricular structure and
      function in patients with essential hypertension.
AB  - Recent experimental studies demonstrated that elevation of plasma aldosterone is
      associated with an increased collagen accumulation resulting in myocardial
      fibrosis. The aim of this study was to evaluate the association of circulating
      aldosterone with cardiac structural and functional changes in patients with
      essential hypertension. The authors examined 39 patients (aged 51 +/- 14 years,
      13 male, 26 female) with essential hypertension. M-mode and two-dimensional
      echocardiography was performed in each subject. Plasma renin activity (PRA) and
      plasma aldosterone (PA) at baseline and after 4 hours upright posture were
      measured. Mean levels of baseline and stimulated PRA were similar in
      hypertensives and control group of normotensives. Baseline and stimulated PA
      levels were mildly but not significantly higher compared to control group. Using
      Tukey Kramer multiple analysis we found a significant positive correlation of
      both baseline and stimulated PA with echocardiographic parameters of left
      ventricle in hypertensive subjects: IVSd (p<0.001), PWd (p<0.001), LVIDd
      (p<0.001) and E/A (p<0.001). However, no correlation between PRA and left
      ventricular structure and function was found in this group of patients. The
      authors conclude that plasma aldosterone levels are related to the structure and
      function of left ventricle. (Tab. 3, Ref. 20.).

PMID- 14594354
TI  - Complications of video-mediastinoscopy--successful management in four cases.
AB  - The authors describe complications of video-mediastinoscopy in a number of
      clinical cases and present case reports of four patients, where this complication
      occurred. The following types of complications were recorded: one case of
      esophageal perforation, one case of tracheal lesion and two cases of massive
      bleeding from central greater vessel. Possibilities of treatment methods of these
      complications, possible ways how to manage and decrease the incidence of life
      threatening complication are being discussed in this paper. (Fig. 5, Ref. 9.).

PMID- 14594355
TI  - Lifestyle of a women--mother and health of members of the family.
AB  - OBJECTIVE: The goal of the study was to evaluate the efficacy of prevention of
      cardiovascular diseases. METHODS: The follow-up study included a sample of 206
      intervened pregnant women. They were given an information booklet about risk
      factors and prevention. During the postpartum period they were contacted again
      and 111 of them completed a questionnaire. Control sample consisted from 200
      women inthe postpartum period not intervened, who filled in the same
      questionnaire. RESULTS AND CONCLUSIONS: Such intervention positively influences
      both attitudes towards lifestyle and knowledge level and can be considered as an
      appropriate preventive measure in pregnant women. The question is, if the
      achieved changes last for a longer time and if they are passed an to members of
      families of the intervened women (Fig. 1, Ref. 8).

PMID- 14594357
TI  - Effect of government actions on technological innovation for SO2 control.
AB  - The relationship between government actions and innovation in environmental
      control technology is important for the design of cost-effective policies to
      achieve environmental goals. This paper examines such relationships for the case
      of sulfur dioxide control technology for U.S. coal-fired power plants. The study
      employs several complementary research methods, including analyses of key
      government actions, technology patenting activity, technology performance and
      cost trends, knowledge transfer activities, and expert elicitations. Our results
      indicate that government regulation appears to be a greater stimulus to inventive
      activity than government-sponsored research support alone, and that the
      anticipation of regulation also spurs inventive activity. Regulatory stringency
      focuses this activity along particular technical pathways and is a key factor in
      creating markets for environmental technologies. We also find that with greater
      technology adoption, both new and existing systems experience notable efficiency
      improvements and capital cost reductions. The important role of government in
      fostering knowledge transfer via technical conferences and other measures is also
      seen as an important factor in promoting environmental technology innovation.

PMID- 14594358
TI  - Intercontinental transport of air pollution: will emerging science lead to a new
      hemispheric treaty?
AB  - We examine the emergence of InterContinental Transport (ICT) of air pollution on
      the agendas of the air quality and climate communities and consider the potential
      for a new treaty on hemispheric air pollution. ICT is the flow of air pollutants
      from a source continent (e.g., North America) to a receptor continent (e.g.,
      Europe). ICT of air pollutants occurs through two mechanisms: (i) episodic
      advection and (ii) increasing the global background, which enhances surface
      concentrations. We outline the current scientific evidence for ICT of aerosols
      and ozone, both of which contribute to air pollution and radiative forcing. The
      growing body of scientific evidence for ICT suggests that a hemispheric-scale
      treaty to reduce air pollutant concentrations may be appropriate to address
      climate and air quality concerns simultaneously. Such a treaty could pave the way
      for future climate agreements.

PMID- 14594359
TI  - Phthalates, alkylphenols, pesticides, polybrominated diphenyl ethers, and other
      endocrine-disrupting compounds in indoor air and dust.
AB  - Chemicals identified as endocrine-disrupting compounds (EDCs) have widespread
      consumer uses, yet little is known about indoor exposure. We sampled indoor air
      and dust in 120 homes, analyzing for 89 organic chemicals identified as EDCs.
      Fifty-two compounds were detected in air and 66 were detected in dust. These are
      the first reported measures in residential environments for over 30 of the
      compounds, including several detected at the highest concentrations. The number
      of compounds detected per home ranged from 13 to 28 in air and from 6 to 42 in
      dust. The most abundant compounds in air included phthalates (plasticizers,
      emulsifiers), o-phenylphenol (disinfectant), 4-nonylphenol (detergent
      metabolite), and 4-tert-butylphenol (adhesive) with typical concentrations in the
      range of 50-1500 ng/m3. The penta- and tetrabrominated diphenyl ethers (flame
      retardants) were frequently detected in dust, and 2,3-dibromo-1-propanol, the
      carcinogenic intermediate of a flame retardant banned in 1977, was detected in
      air and dust. Twenty-three pesticides were detected in air and 27 were detected
      in dust, the most abundant being permethrins and the synergist piperonyl
      butoxide. The banned pesticides heptachlor, chlordane, methoxychlor, and DDT were
      also frequently detected, suggesting limited indoor degradation. Detected
      concentrations exceeded government health-based guidelines for 15 compounds, but
      no guidelines are available for 28 compounds, and existing guidelines do not
      consider endocrine effects. This study provides a basis for prioritizing
      toxicology and exposure research for individual EDCs and mixtures and provides
      new tools for exposure assessment in health studies.

PMID- 14594360
TI  - Statistical evaluation of bacterial source tracking data obtained by rep-PCR DNA
      fingerprinting of Escherichia coli.
AB  - Pattern recognition has been applied to environmental systems for identification
      of numerous pollution sources including aerosolized lead and petroleum
      hydrocarbons. In recent years, DNA fingerprinting has gained widespread
      application as a means to characterize genetic variations for such purposes as
      microbial source tracking. This approach, however, is strongly dependent on the
      statistical and image analyses applied. Several statistical analyses of rep-PCR
      DNA fingerprints were assessed as a means to differentiate between potential
      sources of fecal contamination. GelCompar II and methods based on penalized
      discriminant analysis (PDA) and k-nearest neighbors (KNN) classification
      procedures were used to differentiate between 10 source groups within a library
      containing DNA fingerprints of 548 Escherichia coli isolates from known human and
      nonhuman sources. KNN performed significantly better than PDA in a jackknife
      analysis, though the library was not large enough to detect significant
      differences between GelCompar II and the other two methods. GelCompar II and KNN
      both attained > or = 90% correct classification in a holdout procedure. In
      addition, interpoint distance analyses indicate coherency within source groups,
      while library randomization demonstrated that KNN does not create artificial
      groupings. This investigation stresses the need to understand limitations of
      statistical analyses used in pattern recognition of DNA fingerprints.

PMID- 14594361
TI  - Spatial and temporal trends in short-chain chlorinated paraffins in Lake Ontario
      sediments.
AB  - Short-chain chlorinated paraffins (polychlorinated-[C10-C13]-n-alkanes) were
      measured in Lake Ontario sediments collected during a lake-wide survey to
      characterize spatial and temporal trends in contamination. The Lake Ontario
      average SCCP sediment concentration was 49 ng/g (dry wt), which was somewhat
      higher than the lake-wide average for sigmaDDT (32 ng/g). Individual stations in
      each of the depositional basins exhibited the highest concentrations, ranging
      from 147 ng/g (dry wt) to 410 ng/g at an index station in the Niagara (western)
      basin. Relative average contributions of the carbon chain groups to total SCCPs
      on a lake-wide basis were as follows: sigmaC10 = 24%, sigmaC11 = 35%, sigmaC12 =
      34%, sigmaC13 = 6.6%. Assessment of core profiles and estimates of SCCP fluxes
      indicated that an area of the western end of Lake Ontario is heavily impacted
      (SCCP flux of 170 microg/m2 yr) and potentially influenced by local industrial
      sources of SCCPs. Maximum accumulation of SCCPs in this area of the western basin
      occurred in the mid-1970s. In contrast, SCCP concentrations in a core from a site
      in the central area of the lake (SCCP flux of 8.0 microg/m2 yr) were more similar
      to levels characteristic of remote locations primarily impacted by atmospheric
      sources.

PMID- 14594362
TI  - Thallium in soils and stream sediments of a Zn-Pb mining and smelting area.
AB  - Thallium was determined in 120 samples of soil and 30 samples of stream sediments
      from the southeastern part of the Silesian-Cracowian zinc-lead ore deposits. Soil
      samples were taken from topsoils (0.0-0.2 m) and bottom soils (0.8 and 1.0 m).
      Thallium was determined by flow-injection-differential-pulse anodic stripping
      voltammetry. The samples were decomposed sequentially with 73% hydrofluoric acid
      and a mixture of nitric acid and hydrogen peroxide. The results showed that zinc
      lead ore mining as well as their processing and smelting leads to a significant
      increase of thallium in the top layer of soil and in stream sediments. The
      highest recorded concentration was 150 ppm Tl for stream sediment and 35 ppm for
      a soil sample. Thallium concentration in small rivers from the investigated area
      was by 2 orders of magnitude higher than in the reference area. The highest
      recorded concentration being 3.24 microg L(-1).

PMID- 14594363
TI  - Levels and enantiomeric signatures of methyl sulfonyl PCB and DDE metabolites in
      livers of harbor porpoises (Phocoena phocoena) from the Southern North Sea.
AB  - The concentration of 26 methyl sulfonyl metabolites of polychlorinated biphenyls
      (MeSO2-PCBs) and of p,p'-DDE (MeSO2-DDE) were determined in 19 liver samples from
      harbor porpoises (Phocoena phocoena) stranded between 1997 and 2000 on the
      Belgian and French North Sea Coasts. The total concentration of MeSO2-PCBs ranged
      from 39 to 4221 ng/g lipid weight (lw) and were generally higher in adults (age >
      2 yr, range 969-4,221 ng/g lw) than in juveniles (age < 2 yr, range 39-1815 ng/g
      lw). The concentrations of MeSO2-DDE were generally also higher in adults (21-96
      ng/g lw) than in juveniles (0.5-60 ng/g lw). Congeners 3- and 4-MeSO2-CB101 were
      the dominating metabolites in all samples. Due to their preferential retention in
      the liver, the MeSO2-PCB congeners could be divided into two groups. The first
      group was dominated by the 3-MeSO2-PCB congeners and consisted of MeSO2-CB31, 
      CB49, -CB52, -CB87, and -CB101, which all have a 2,5-chlorine substitution in the
      phenyl ring containing the methyl sulfonyl group. The second group was dominated
      by the 4-MeSO2-PCB congeners and consisted of MeSO2-CB64, -CB91, -CB110, and 
      CB132, which all have a 2,3,6-chlorine substitution. The ratios of sum of
      PCBs/sum of MeSO2-PCBs and p,p'-DDE/MeSO2-DDE differed greatly between individual
      subjects and ranged from 15 to 419 and from 17 to 1088, respectively. The ratio
      between the precursor PCB congeners and their corresponding metabolites ranged
      from 0.6 (CB49) to 175 (CB174). Enantiomeric fractions (EFs) for MeSO2-PCB
      atropisomers, which include 3-MeSO2-CB132, 3-MeSO2-CB149, 4-MeSO2-CB149, 3-MeSO2
      CB174, and 4-MeSO2-CB174, were also measured in 8 out of the 19 subjects. High
      enantiomeric excess (EF > 0.73 or EF < 0.23) for the measured chiral MeSO2-PCB
      congeners was found in all samples. This result may suggest that one atropisomer
      may be preferentially formed in harbor porpoises or that the atropisomers are
      retained in a highly selective manner.

PMID- 14594364
TI  - Exposure of Taiwan residents to polychlorinated biphenyl congeners from farmed,
      ocean-caught, and imported fish.
AB  - This study is to assess PCB levels in five frequently consumed fish species in
      Taiwan, tilapia, milkfish, white pomfret, hairtail, and cod. Seventeen congeners
      were measured in fillet samples purchased from major markets in northern,
      central, and southern Taiwan. All 136 samples had traces of PCBs. The median
      concentrations were 0.18, 0.46, 0.62, 0.69, and 7.34 ng/g wet wt and 1.01, 0.28,
      1.14, 5.06, and 19.3 pg-WHO-TEQ/g lipid in tilapia, milkfish, white pomfret,
      hairtail, and cod samples, respectively. Cod (the imported fish) had the highest
      wet weight PCB concentrations. The fish caught off-shore (white pomfret and
      hairtail) had higher levels than the farmed fish (tilapia and milkfish). The
      congener profiles varied among species. PCB 105/153 and 126 accounted for more
      than 28% and 53% of the 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents (WHO
      TEQs) in hairtail and cod, respectively; while PCB 156 was the major TEQ
      contributor in the other species. The estimated median PCB intake of the general
      public from consumption of the five species ranged from 0.000023 to 0.048 pg-WHO
      TEQ/kg/day. It was also found that samples farmed or caught along the southern
      coast had higher PCB levels than those from other parts of Taiwan, indicating
      possible elevated PCB contamination around that area.

PMID- 14594365
TI  - Isotopic tracing of landfill leachates and pollutant lead mobility in soil and
      groundwater.
AB  - Here we provide evidence of the capability of stable lead isotopes to trace
      landfill leachate in a shallow groundwater. The municipal landfill we have
      investigated is located in southeastern France. It has no bottom liner, and
      wastes are placed directly on the ground. Stable lead isotopes allow the
      characterization of this landfill leachate signature (206Pb/207Pb = 1.189 +/-
      0.004) that is clearly different from that of the local atmosphere (206Pb/207Pb =
      1.150 +/- 0.006) and crustal lead (206Pb/207Pb = 1.200 +/- 0.005). Piezometers
      located in the direct vicinity of the landfill generally display this contaminant
      imprint. The landfill plume is monitored up to 1000 m downgradient of the
      landfill, in very good agreement with evaluation from chloride concentration.
      Meanwhile, 206Pb/207Pb ratios measured at a piezometer located 4600 m
      downgradient of the landfill suggest a contamination by the landfill plume. This
      result shows that the complexity of a pollutant plume dispersion in this shallow
      groundwater system requires several independent tracers to clearly resolve origin
      and transport pathways for contaminants. Furthermore, seasonal rainfall variation
      for this Mediterranean mixed Quaternary alluvion reservoir and the use of KCl
      fertilizers might favor an efficient remobilization of atmospheric lead in plowed
      soils and its transfer into groundwater as shown by lead isotope systematics.

PMID- 14594366
TI  - Reduction of crop contamination by soil resuspension within the 30-km zone of the
      Chernobyl nuclear power plant.
AB  - A field experiment was conducted within the 30-km zone of the Chernobyl Nuclear
      Power Plant to analyze whether the application of mulching reduced resuspension
      of 137Cs contaminated soil in oat (Avena sativa) crops. In 1993, we applied a
      mulch treatment at a dose of 200 g m(-2), and soil resuspension was measured by
      estimating soil loadings onto plant surfaces from Ti concentrations in plants. In
      1994, two mulch doses were applied, 200 and 50 g m(-2), and we estimated the
      contribution of soil resuspension by using artificial resuspension collection
      devices (ARC). In the 1993 experiment between 4.6 and 34.4% of the plant's total
      137Cs contamination was attributed to external soil contamination. The mean
      amount of soil-derived 137Cs attached to vegetation was 124.7 Bq kg(-1)(plant) in
      control plots and 53.7 Bq kg(-1)(plant) in mulched plots. In the 1994 experiment,
      covering the soil with a mulch layer decreased the radiocesium content in ARC by
      about 70%. Results obtained in these experiments suggest that soil resuspension
      was a significant mechanism for plant contamination and that mulching was
      effective in reducing that contamination.

PMID- 14594367
TI  - Global distribution of radionuclides (137Cs and 40K) in marine mammals.
AB  - Concentrations of anthropogenic radionuclides were measured in the muscle of
      marine mammals collected from various locations all over the world, and the
      global distribution of 137Cs in marine mammals was investigated. 40K was detected
      in all the specimens of marine mammals with no apparent difference between
      regions. An anthropogenic radionuclide, 137Cs, was detected in most of the
      species of marine mammals. With regard to the worldwide distribution of 137Cs,
      the highest concentration was noticed in the U.K. coast, followed by Lake Baikal,
      and decreases toward the southern sampling points. A strong positive correlation
      was observed between 137Cs levels in the muscle of marine mammals and the ambient
      seawater. Marine mammals feeding on fishes showed a higher concentration factor
      (CF) for 137Cs than those feeding on cephalopods. To our knowledge, this is the
      first report on the global distribution of 137Cs and the effect of feeding habits
      on the CF values of 137Cs in marine mammals.

PMID- 14594368
TI  - Levels and temporal trends of toxaphene congeners in beluga whales
      (Delphinapterus leucas) from the St. Lawrence Estuary, Canada.
AB  - Environmentally relevant toxaphene congeners were determined in blubber samples
      of stranded beluga whales (Delphinapterus leucas) from the St. Lawrence Estuary
      (SLE), Canada. The purpose of this study was to evaluate the levels and the
      temporal trends (1988-1999) of a suite of six chlorobornanes (P26, P40/41, P44,
      P50, and P62) in the SLE belugas. P26 and P50 mean concentrations were in the
      same range as those reported for animals living in the Arctic environment
      suggesting that the atmospheric transport represents the main input of toxaphene
      to the SLE. A general exponential decline of chlorobornane concentrations in
      belugas was observed, except for P26 and P50 in males. On average, concentrations
      decreased by a factor of two in 8.5 years during the 1988-1999 time period. This
      rate of decline is similar to the reduction of toxaphene emission from
      agricultural soils in the southern United States reported over the same time
      period. Some differences in decline rates were observed among the studied CHB
      congeners. For instance, P62 decreased more rapidly than P26 and P50 in both male
      and female belugas. Several hypotheses were advanced to explain these differences
      such as selective metabolism of specific chlorobornanes by SLE belugas or their
      prey. However, a most likely explanation is the selective degradation of the
      technical product in soils and atmosphere in the source region.

PMID- 14594369
TI  - Photochemical production of Fe(II) in rainwater.
AB  - Significant concentrations of Fe(II) were produced upon irradiation of authentic
      rainwater with simulated sunlight. The magnitude of photoproduction was dependent
      on initial Fe(II), Fe(III), and hydrogen ion concentrations, with more Fe(II)
      photoproduction when initial Fe(III) and H+ concentrations were high and initial
      Fe(II) concentrations were low. An equation was developed that accurately
      predicts photoproduction of Fe(II) in rainwater based on initial Fe speciation
      values and pH. The quantum yield of Fe(II) photochemical production in rain
      decreased dramatically with increasing wavelength and decreasing energy of
      incoming radiation with the average quantum yield at 265 nm approximately an
      order of magnitude greater than at 546 nm. Probable photochemical precursors of
      Fe(II) in authentic rain include iron(III) oxalate, iron(III) hydroxide, and an
      undefined Fe(III) complex. The wavelength-dependent Fe(II) production was modeled
      using the average Fe(II) efficiency spectrum, an average rainwater absorption
      spectrum, and the modeled actinic flux for temperate latitudes in both summer and
      winter. The response spectrum has the highest photoproduction of Fe(II) in summer
      and winter at 325 and 330 nm, respectively, with greater production in summer
      rain due to increased actinic flux and longer hours of irradiation.

PMID- 14594370
TI  - Assessing the ecotoxicity of pesticide transformation products.
AB  - Once released to the environment, pesticides may be degraded by abiotic and
      biotic processes. While parent compounds are assessed in detail in many
      regulatory schemes, the requirements for the assessment of transformation
      products are less well developed. This study was therefore performed to explore
      the relationships between the toxicity of transformation products and their
      parent compounds and to develop a pragmatic approach for use in the risk
      assessment of transformation products. Data were obtained on the properties and
      ecotoxicity of transformation products arising from a wide range of pesticides.
      Generally, transformation products were less toxic to fish, daphnids, and algae
      than their parent compound. In instances where a product was more toxic, the
      increase in toxicity could be explained by either (1) the presence of a pesticide
      toxicophore; (2) the fact that the product is the active part of a propesticide;
      (3) the product is accumulated to a greater extent than the parent compound; or
      (4) the product has a more potent mode of action than the parent. On the basis of
      the findings, an approach has been proposed to estimate the ecotoxicity of
      transformation products based on chemical structure and data on the toxicity of
      the parent compound. The assessments can be performed at an early stage in the
      risk assessment process to identify those substances that require further
      testing.

PMID- 14594371
TI  - Evaluation of two methods for prediction of bioaccumulation factors.
AB  - Two methods for deriving bioaccumulation factors (BAFs) used by the U.S.
      Environmental Protection Agency in development of water quality criteria were
      evaluated using polychlorinated biphenyl (PCB) data from the Hudson River and
      Green Bay ecosystems. One method predicts BAF(L)fd values (BAFs based upon
      concentrations of freely dissolved chemical in ambient water and in the lipid
      fraction of tissue) using field-measured biota-sediment accumulation factors
      (BSAFs): greater than 90% of the predicted BAF(L)fd values were within a factor
      of 5 of their measured values for both ecosystems. The second method predicts
      BAF(L)fd values as the chemical's 1-octanol/water partition coefficient (Kow)
      times a food chain multiplier: greater than 90% of the predicted BAF(L)fd values
      were within a factor of 5 of their measured values for the Green Bay ecosystem
      and for three of the six sampling locations on the Hudson River. Poorer
      predictive ability with the Kow method for the other three sampling locations was
      believed to be due to the existence of environmental conditions not
      representative of the longer term ecosystem conditions assumed for the method.
      BAF(L)fd and BAF(T)t values (BAFs based upon concentrations of total chemical in
      ambient water and in wet tissue) were compared. The within ecosystem and across
      ecosystems comparisons demonstrated a 2-5-fold decrease in variability (expressed
      as ratios of coefficients of variation, percentile ranges, and confidence ranges)
      for predicted BAF(L)fd values in comparison to BAF(T)t values.

PMID- 14594372
TI  - New processes in the environmental chemistry of nitrite. 2. The role of hydrogen
      peroxide.
AB  - The oxidation of nitrite and nitrous acid to *NO2 upon irradiation of dissolved
      Fe(III), ferric (hydr)oxides, and nitrate has previously been shown to enhance
      phenol nitration. This allowed the proposal of a new role for nitrite and nitrous
      acid in natural waters and atmospheric aerosols. This paper deals with the
      interaction between hydrogen peroxide, a key environmental factor in atmospheric
      oxidative chemistry, and nitrite/nitrous acid. The reaction between nitrous acid
      and hydrogen peroxide yields peroxynitrous acid, a powerful nitrating agent and
      an important intermediate in atmospheric chemistry. The kinetics of this reaction
      is compatible with a rate-determining step involving either H3O2+ and HNO2 or
      H2O2 and protonated nitrous acid. In the former case the rate constant between
      the two species would be 179.6 +/- 1.4 M(-1) s(-1), in the latter case it would
      be as high as (1.68 +/- 0.01) x 10(10) M(-1) s(-1) (diffusion-controlled
      reaction). Due to the more reasonable value of the rate constant, the reaction
      between H3O2+ and HNO2 seems more likely. In the presence of HNO2 + H2O2 the
      nitration of phenol is strongly enhanced when compared with HNO2 alone. The
      nitration rate of phenol in the presence of peroxynitrous acid decreases as pH
      increases, thus HOONO is a potential source of atmospheric nitroaromatic
      compounds in acidic water droplets. The mixture Fe(II) + H2O2 (Fenton reagent)
      can oxidize nitrite and nitrous acid to nitrogen dioxide, which results in phenol
      nitration. The nitration in the presence of Fe(II) + H2O2 + NO2-/HNO2 occurs more
      rapidly than the one with H2O2 + NO2-/HNO2 at pH 5, where little HNO2 is
      available to directly react with hydrogen peroxide. Both systems, however, are
      more effective than NO2-/HNO2 alone in producing nitrophenols from phenol.
      Another process leading to the oxidation of nitrite to nitrogen dioxide is the
      photo-Fenton one. It can be relevant at pH > or = 6, as nitrite does not react
      with H2O2 at room temperature. Under such conditions the source of Fe(II) is the
      photolysis of ferric (hydr)oxides (heterogeneous photo-Fenton reaction). In the
      presence of nitrite this reaction induces very effective nitrophenol formation
      from phenol.

PMID- 14594373
TI  - Molecular-scale characterization of uranium sorption by bone apatite materials
      for a permeable reactive barrier demonstration.
AB  - Uranium binding to bone charcoal and bone meal apatite materials was investigated
      using U L(III)-edge EXAFS spectroscopy and synchrotron source XRD measurements of
      laboratory batch preparations in the absence and presence of dissolved carbonate.
      Pelletized bone char apatite recovered from a permeable reactive barrier (PRB) at
      Fry Canyon, UT, was also studied. EXAFS analyses indicate that U(VI) sorption in
      the absence of dissolved carbonate occurred by surface complexation of U(VI) for
      sorbed concentrations < or = 5500 microg U(VI)/g for all materials with the
      exception of crushed bone char pellets. Either a split or a disordered equatorial
      oxygen shell was observed, consistent with complexation of uranyl by the apatite
      surface. A second shell of atoms at a distance of 2.9 A was required to fit the
      spectra of samples prepared in the presence of dissolved carbonate (4.8 mM total)
      and is interpreted as formation of ternary carbonate complexes with sorbed U(VI).
      A U-P distance at 3.5-3.6 A was found for most samples under conditions where
      uranyl phosphate phases did not form, which is consistent with monodentate
      coordination of uranyl by phosphate groups in the apatite surface. At sorbed
      concentrations > or = 5500 microg U(VI)/g in the absence of dissolved carbonate,
      formation of the uranyl phosphate solid phase, chernikovite, was observed. The
      presence of dissolved carbonate (4.8 mM total) suppressed the formation of
      chernikovite, which was not detected even with sorbed U(VI) up to 12,300 microg
      U(VI)/g in batch samples of bone meal, bone charcoal, and reagent-grade
      hydroxyapatite. EXAFS spectra of bone char samples recovered from the Fry Canyon
      PRB were comparable to laboratory samples in the presence of dissolved carbonate
      where U(VI) sorption occurred by surface complexation. Our findings demonstrate
      that uranium uptake by bone apatite will probably occur by surface complexation
      instead of precipitation of uranyl phosphate phases under the groundwater
      conditions found at many U-contaminated sites.

PMID- 14594374
TI  - Impact of transition metals on reductive dechlorination rate of hexachloroethane
      by mackinawite.
AB  - Mackinawite, an iron monosulfide, has been shown to be a potential reductant for
      chlorinated organic compounds under anaerobic conditions. Chlorinated organic
      compounds are often found with inorganic contaminants. This study investigates
      the impact of various transition metals on the reductive dechlorination by
      mackinawite using a readily degradable chlorinated organic compound,
      hexachloroethane (HCA). Different classes of transition metals show distinct
      patterns in their impact on the HCA dechlorination: 10(-3) M Cr(III) and Mn(II)
      (hard metals) decreased the dechlorination rates, while 10(-4), 10(-3), and 10(
      2) M Co(II), Ni(II), Cu(II), Zn(II), Cd(II), and Hg(II) (intermediate/soft
      metals) increased the rates. The tested hard metals, due to their weak affinity
      for sulfides, are thought to form surface precipitates of hydroxides around FeS
      under the experimental conditions with these hydroxides hindering the electron
      transfer between FeS and HCA. Due to their high affinity for sulfides, however,
      the tested intermediate/soft metals can react with FeS in various ways:
      precipitation of pure metal sulfides (MS), formation of metal-substituted FeS by
      lattice exchange, and coprecipitation of the mixed sulfides in a Fe-M-S system.
      Fe(II), released as a result of the interaction of FeS with intermediate/soft
      metals, enhances the HCA dechlorination at the doses of 10(-4) and 10(-3) M
      through sorbed or dissolved Fe(II) species, while Fe(OH)2(s) formed at the higher
      dose of 10(-2) M also enhances the reductive dechlorination. Rate increases
      observed in Co(II)-, Ni(II)-, and Hg(II)-amended systems are not simply explained
      by the formation of pure MS; instead, metal-substituted FeS or coprecipitated
      sulfides are thought to be responsible for the significantly increased rates
      observed in these systems.

PMID- 14594375
TI  - Sediment characteristics affecting desorption kinetics of select PAH and PCB
      congeners for seven laboratory spiked sediments.
AB  - Measures of desorption are currently considered important as potential surrogates
      for bioaccumulation as measures of the bioavailability of sediment-sorbed
      contaminants. This study determined desorption rates of four laboratory spiked
      compounds, benzo[a]pyrene (BaP), 2,4,5,2',4',5'-hexachlorobiphenyl (HCBP),
      3,4,3',4'-tetrachlorobiphenyl (TCBP), and pyrene (PY), to evaluate the effect of
      sediment characteristics. The compounds were sorbed onto seven sediments with a
      broad range of characteristics. Desorption was measured by Tenax-TA extraction
      from aqueous sediment suspensions. Desorption rates were modeled using an
      empirical three compartment model describing operationally defined rapid, slow,
      and very slow compartments. The sediments were characterized for plant pigments,
      organic carbon (OC), total nitrogen (TN), lipids, NaOH extractable residue,
      lignin, amino acids, soot carbon, and particle size fractions. Desorption from
      the rapid compartment for each of the planar compounds BaP, PY, and TCBP was
      significantly correlated to sediment characteristics that could be considered to
      represent younger (i.e., less diagenetically altered) organic matter, e.g., plant
      pigment, lipid, and lignin contents. However, for these compounds there were no
      significant correlations between desorption and OC, TN, soot carbon, or amino
      acid contents. HCBP desorption was different from the three planar molecules. For
      HCBP, the flux from the rapid compartment was negatively correlated (0.1 > p >
      0.05) with the OC content of the sediment. Overall, HCBP desorption was dominated
      by the amount of OC and the particle size distribution of the sediments, while
      desorption of the planar compounds was dominated more by the compositional
      aspects of the organic matter.

PMID- 14594376
TI  - Hydroxyaldehyde products from hydroxyl radical reactions of Z-3-hexen-1-ol and 2
      methyl-3-buten-2-ol quantified by SPME and API-MS.
AB  - Hydroxyaldehyde products of the OH radical-initiated reactions (in the presence
      of NO) of two volatile vegetative emissions, Z-3-hexen-1-ol and 2-methyl-3-buten
      2-ol, were examined to assess the qualitative and quantitative potential of two
      analysis techniques (1) sampling by Solid-Phase MicroExtraction (SPME) with on
      fiber derivatization followed by gas chromatographic analyses and (2) in situ
      analysis by negative ion mode atmospheric pressure ionization mass spectrometry
      (API-MS). The compounds were chosen because reaction mechanisms predict
      hydroxyaldehyde products, and reliable coproduct yield data are available. The
      API-MS analyses showed product ion peaks attributed to the NO2- adducts of 3
      hydroxypropanal and dihydroxynitrates from Z-3-hexen-1-ol, and a formation yield
      of 3-hydroxypropanal of 44% was derived. Product ion peaks attributed to NO2-
      adducts of glycolaldehyde [HOCH2CHO], 2-hydroxy-2-methylpropanal
      [(CH3)2C(OH)CHO], and dihydroxynitrates were observed by API-MS from 2-methyl-3
      buten-2-ol, and a formation yield of 2-hydroxy-2-methylpropanal of 16% was
      obtained. In experiments with SPME sampling, the formation yields of
      hydroxycarbonyls measured as their oxime derivatives were as follows: from Z-3
      hexen-1-ol, propanal, 56 +/- 8%; 3-hydroxypropanal, 101 +/- 24%; and from 2
      methyl-3-buten-2-ol, 2-hydroxy-2-methylpropanal, 31 +/- 4%. Both the API-MS and
      SPME analyses provided product information, and hydroxycarbonyl yields from the
      SPME data are in reasonable agreement with previously measured formation yields
      of coproducts.

PMID- 14594377
TI  - Simulating secondary organic aerosol activation by condensation of multiple
      organics on seed particles.
AB  - The conditions under which semivolatile organic gases condense were studied in a
      Teflon particle chamber by scanning mobility particle sizing (SMPS) of the
      resultant particles. Benzaldehyde, maleic and citraconic anhydrides, n-decane,
      trans-cinnamaldehyde, and citral were introduced in various combinations into a
      particle chamber containing either particle-free nitrogen or nitrogen with dry
      seed particles made out of sodium chloride, D-tartartic acid, ammonium sulfate,
      or 1,10-decanediol. No organic gas was allowed to reach its saturation point
      relative to the vapor pressure of its pure liquid in any experiment. In the
      absence of seed particles, organic aerosol particles formed by ternary nucleation
      when the sum of the individual organic saturation levels reached a threshold
      between 1.17 and 1.86. With seed particles present, particle sizes began to
      increase when the sum of organic saturation levels reached 1.0. This size
      increase corresponds to the establishment and activation of ternary organic
      layers on the "clean" seed particles, as predicted by absorption partitioning
      theory. The observed increases in particle volume depended on initial seed
      particle volume, indicating that either gas diffusion rates or chemical reactions
      were controlling the rate of uptake.

PMID- 14594378
TI  - Electron spin resonance study of chromium(V) formation and decomposition by
      basalt-inhabiting bacteria.
AB  - Bacterial reduction of Cr(VI) to Cr(III) compounds may produce reactive
      intermediates Cr(V) and Cr(IV), which can affect the mobility and toxicity of
      chromium in environments. To address this important subject, we conducted an
      electron spin resonance (ESR) study to understand the kinetics of the formation
      and decomposition of Cr(V) during Cr(VI) reduction by different gram-positive
      Cr(VI)-tolerant bacteria, which were isolated from polluted basalts from the
      United States of America and the Republic of Georgia. Results from our batch
      experiments show that during Cr(VI) reduction, the macromolecules at the cell
      wall of these bacteria could act as an electron donor to Cr(VI) to form a stable
      square-pyramidal Cr(V) complexes, which were reduced further probably via a one
      electron transfer pathway to form Cr(IV) and Cr(III) compounds. The Cr(V) peak at
      the ESR spectrum possessed superhyperfine splitting characteristic of the Cr(V)
      complexes with diol-containing molecules. It appears that the kinetics of Cr(V)
      formation and decomposition depended on the bacterial growth phase and on the
      species. Both formation and decomposition of Cr(V) occurred more quickly when
      Cr(VI) was added at the exponential phase. In comparison with other gram-positive
      bacteria from the republic of Georgia, the formation and decomposition of Cr(V)
      in Arthrobacter species from the Unites States was significantly slower.

PMID- 14594379
TI  - Critical conceptualism in environmental modeling and prediction.
AB  - Many important problems in environmental science and engineering are of a
      conceptual nature. Research and development, however, often becomes so
      preoccupied with technical issues, which are themselves fascinating, that it
      neglects essential methodological elements of conceptual reasoning and
      theoretical inquiry. This work suggests that valuable insight into environmental
      modeling can be gained by means of critical conceptualism which focuses on the
      software of human reason and, in practical terms, leads to a powerful
      methodological framework of space-time modeling and prediction. A knowledge
      synthesis system develops the rational means for the epistemic integration of
      various physical knowledge bases relevant to the natural system of interest in
      order to obtain a realistic representation of the system, provide a rigorous
      assessment of the uncertainty sources, generate meaningful predictions of
      environmental processes in space-time, and produce science-based decisions. No
      restriction is imposed on the shape of the distribution model or the form of the
      predictor (non-Gaussian distributions, multiple-point statistics, and nonlinear
      models are automatically incorporated). The scientific reasoning structure
      underlying knowledge synthesis involves teleologic criteria and stochastic logic
      principles which have important advantages over the reasoning method of
      conventional space-time techniques. Insight is gained in terms of real world
      applications, including the following: the study of global ozone patterns in the
      atmosphere using data sets generated by instruments on board the Nimbus 7
      satellite and secondary information in terms of total ozone-tropopause pressure
      models; the mapping of arsenic concentrations in the Bangladesh drinking water by
      assimilating hard and soft data from an extensive network of monitoring wells;
      and the dynamic imaging of probability distributions of pollutants across the
      Kalamazoo river.

PMID- 14594381
TI  - Evaluation of specific ultraviolet absorbance as an indicator of the chemical
      composition and reactivity of dissolved organic carbon.
AB  - Specific UV absorbance (SUVA) is defined as the UV absorbance of a water sample
      at a given wavelength normalized for dissolved organic carbon (DOC)
      concentration. Our data indicate that SUVA, determined at 254 nm, is strongly
      correlated with percent aromaticity as determined by 13C NMR for 13 organic
      matter isolates obtained from a variety of aquatic environments. SUVA, therefore,
      is shown to be a useful parameter for estimating the dissolved aromatic carbon
      content in aquatic systems. Experiments involving the reactivity of DOC with
      chlorine and tetramethylammonium hydroxide (TMAH), however, show a wide range of
      reactivity for samples with similar SUVA values. These results indicate that,
      while SUVA measurements are good predictors of general chemical characteristics
      of DOC, they do not provide information about reactivity of DOC derived from
      different types of source materials. Sample pH, nitrate, and iron were found to
      influence SUVA measurements.

PMID- 14594380
TI  - Modeling precipitation and sorption of elements during mixing of river water and
      porewater in the Coeur d'Alene River basin.
AB  - Reddish brown flocs form along the edge of the Coeur d'Alene River when porewater
      drains into river water during the annual lowering of water level in the basin.
      The precipitates are efficient scavengers of dissolved elements and have
      characteristics that may make metals associated with them bioavailable. This work
      characterizes the geochemistry of the porewater and models the formation and
      composition of the flocs. Porewater is slightly acidic, has suboxic to anoxic
      characteristics, tends to have higher alkalinity, and contains elevated
      concentrations of many constituents relative to river water. Laboratory mixing
      experiments involving porewater and river water were done to produce the
      precipitates. Thermodynamic predictions using PHREEQC indicate that predicted
      amounts of ferrihydrite and gibbsite agree with removal of Fe and Al. Predictions
      of element removal by adsorption onto ferrihydrite are consistent with observed
      removal using a combination of surface complexation constants for the generalized
      two-layer model (As and Se), alternative surface constants derived from
      experiments at high sorbate-to-sorbent ratios (Cd, Co, Cu, Ni, Pb, and Zn), and
      adjusted surface constants to fit experimental data (Cr, Mo, and Sb). This new
      set of surface complexation constants needs further testing in other contaminated
      systems.

PMID- 14594382
TI  - Critical evaluation of the ability of sequential extraction procedures to
      quantify discrete forms of selenium in sediments and soils.
AB  - Sequential extraction procedures (SEPs) have been widely used to characterize the
      mobility, bioavailibility, and potential toxicity of trace elements in soils and
      sediments. Although oft-criticized, these methods may perform best with redox
      labile elements (As, Hg, Se) for which more discrete biogeochemical phases may
      arise from variations in oxidation number. We critically evaluated two published
      SEPs for Se for their specificity and precision by applying them to four discrete
      components in an inert silica matrix: soluble Se(VI) (selenate), Se(IV)
      (selenite) adsorbed onto goethite, elemental Se, and a metal selenide (FeSe;
      achavalite). These were extracted both individually and in a mixed model
      sediment. The more selective of the two procedures was modified to further
      improve its selectivity (SEP 2M). Both SEP 1 and SEP 2M quantitatively recovered
      soluble selenate but yielded incomplete recoveries of adsorbed selenite (64% and
      81%, respectively). SEP 1 utilizes 0.1 M K2S2O8 to target "organically
      associated" Se, but this extractant also solubilized most of the elemental (64%)
      and iron selenide (91%) components of the model sediment. In SEP 2M, the Na2SO3
      used in step III is effective in extracting elemental Se but also extracted 17%
      of the Se from the iron selenide, such that the elemental fraction would be
      overestimated should both forms coexist. Application of SEP 2M to eight wetland
      sediments further suggested that the Na2SO3 in step III extracts some organically
      associated Se, so a NaOH extraction was inserted beforehand to yield a further
      modification, SEP 2OH. Results using this five-step procedure suggested that the
      four-step SEP 2M could overestimate elemental Se by as much as 43% due to
      solubilization of organic Se. Although still imperfect in its selectivity, SEP
      20H may be the most suitable procedure for routine, accurate fractionation of Se
      in soils and sediments. However, the strong oxidant (NaOCl) used in the final
      step cannot distinguish between refractory organic forms of Se and pyritic Se
      that might form under sulfur-reducing conditions.

PMID- 14594383
TI  - Evaluation of fluorescence quenching for assessing the importance of interactions
      between nonpolar organic pollutants and dissolved organic matter.
AB  - The assumptions behind the fluorescence quenching (FQ) method were thoroughly
      evaluated to assess its potential for quickly and accurately assessing the
      importance of hydrophobic organic contaminant-macromolecular organic carbon
      interactions in aquatic systems. Perylene was used as the probe molecule to avoid
      problems encountered with other fluorescent probes. Results from a wide range of
      wetland samples suggest that static quenching dominates, that other quenchers do
      not interfere with analyses, and that full quenching on sorption does not occur
      for all samples. The latter result indicates that the quantum yield of the sorbed
      probe must be accounted for in quantifying the magnitude of Kmoc values by FQ.
      Observed Kmoc values compared favorably with those measured by the solubility
      enhancement method. Overall, our results suggest that FQ can be used as a quick
      and reliable screening tool as long as precautions are taken to ensure the
      validity of the results.

PMID- 14594384
TI  - Use of time- and chemically resolved particulate data to characterize the
      infiltration of outdoor PM2.5 into a residence in the San Joaquin Valley.
AB  - Recent studies associate particulate air pollution with adverse health effects.
      The indoor exposure to particles of outdoor origin is not well-characterized,
      particularly for individual chemical species. In response to this, a field study
      in an unoccupied, single-story residence in Clovis, CA, was conducted. Real-time
      particle monitors were used both outdoors and indoors to quantity PM2.5 nitrate,
      sulfate, and carbon. The aggregate of the highly time-resolved sulfate data, as
      well as averages of these data, was fit using a time-averaged form of the
      infiltration equation, resulting in reasonable values for the penetration
      coefficient and deposition loss rate. In contrast, individual values of the
      indoor/outdoor ratio can vary significantly from that predicted by the model for
      time scales ranging from a few minutes to several hours. Measured indoor ammonium
      nitrate levels were typically significantly lower than expected solely on the
      basis of penetration and deposition losses. The additional reduction is due to
      the transformation of ammonium nitrate into ammonia and nitric acid gases
      indoors, which are subsequently lost by deposition and sorption to indoor
      surfaces. This result illustrates that exposure assessments based on total
      outdoor particle mass can obscure the actual causal relationships for indoor
      exposures to particles of outdoor origin.

PMID- 14594385
TI  - Detection of 2,4,6-trinitrotoluene in environmental samples using a homogeneous
      fluoroimmunoassay.
AB  - We have tested both soil and water environmental samples for 2,4,6
      trinitrotoluene (TNT) using a simple homogeneous assay. This assay is based on
      changes in fluorescence emission intensity when a fluorescently labeled TNT
      analogue, bound to an anti-TNT antibody, is competitively displaced by TNT.
      Fluoroimmunoassay results for TNT concentrations in diluted acetone extracts
      prepared from archived soils were in good agreement with the results from high
      performance liquid chromatography analysis of the same sample extracts. In
      addition, assays of TNT-spiked environmental well water gave results essentially
      identical with assays conducted in a TNT-spiked laboratory buffer. The
      homogeneous fluoroimmunoassay, which is rapid, simple, sensitive, and amenable to
      high throughput screening, shows promise for near real-time evaluation of TNT
      contamination in environmental samples.

PMID- 14594386
TI  - Real-time PCB monitoring using time-of-flight mass spectrometry with picosecond
      laser ionization.
AB  - The study demonstrates the applicability of laser ionization time-of-flight mass
      spectrometry for real-time measurement of polychlorinated biphenyls (PCBs).
      Picosecond 266-nm laser light ionization reduced fragmentation and provided very
      high PCB detection sensitivity. This high sensitivity has advantages in terms of
      real-time monitoring capability as compared to the conventional GC-ECD or GC-MS
      methods, which require at least several days for the analysis of PCBs. Detection
      sensitivity of under 0.01 mg/Nm3 was achieved with a 1-min measuring time; this
      sensitivity is superior to the exhaust gas control guideline of 0.15 mg/Nm3 by a
      factor of 10. A prototype PCB monitoring device has been developed and tested in
      a pilot PCB treatment plant. The 1-min detection time represents a substantial
      advance in the monitoring of exhaust gas and the workplace atmosphere in
      accordance with safety regulations.

PMID- 14594387
TI  - Development of a set of simple bacterial biosensors for quantitative and rapid
      measurements of arsenite and arsenate in potable water.
AB  - Testing for arsenic pollution is commonly performed with chemical test kits of
      unsatisfying accuracy. Bacterial biosensors are an interesting alternative as
      they are easily produced, simple, and highly accurate devices. Here, we describe
      the development of a set of bacterial biosensors based on a nonpathogenic
      laboratory strain of Escherichia coli, the natural resistance mechanism of E.
      coli against arsenite and arsenate, and three reporter proteins: bacterial
      luciferase, beta-galactosidase and Green Fluorescent Protein (GFP). The
      biosensors were genetically optimized to reduce background expression in the
      absence of arsenic. In calibration experiments with the biosensors and arsenite
      amended potable water, arsenite concentrations at 4 microg of As/L (0.05 microM)
      were routinely and accurately measured. The currently most quantitative system
      expressed the bacterial luciferase as reporter protein, responding proportional
      with a concentration range between 8 and 80 microg of As/L. Sensor cells could be
      stored as frozen batches, resuspended in plain media, and exposed to the aqueous
      test sample, and light emission was measured after 30-min incubation. Field
      testing for arsenite was achieved with a system that contained beta
      galactosidase, producing a visible blue color at arsenite concentrations above 8
      microg/L. For this sensor, a protocol was developed in which the sensor cells
      were dried on a paper strip and placed in the aqueous test solution for 30 min
      after which time color development was allowed to take place. The GFP sensor
      showed good potential for continuous rather than end point measurements. In all
      cases, growth of the biosensors and production of the strip test was achieved by
      very simple means with common growth media, and quality control of the sensors
      was performed by isolating the respective plasmids with the genetic constructs
      according to simple standard genetic technologies. Therefore, the biosensor cells
      and protocols may offer a realistic alternative for measuring arsenic
      contamination in potable water.

PMID- 14594388
TI  - Sequential chemical oxidation and aerobic biodegradation of equivalent carbon
      number-based hydrocarbon fractions in jet fuel.
AB  - Remediation of petroleum mixtures is complicated by the differing environmental
      degradabilities of hundreds of individual hydrocarbons in the mixtures. By
      grouping the individual hydrocarbons into a few fractions based on equivalent
      carbon number (EC), the present study examined the chemical and biological
      degradation of the fractions. With or without prechemical oxidation (25 days) by
      three oxidants (KMnO4, H202, MgO2), sterile and live microcosms were constituted
      with aquifer samples for aerobic biodegradation (134 days) of JP-4 jet fuel.
      Eighty-seven hydrocarbons were recovered and grouped into nine EC fractions. The
      apparent removal and actual transformation rate constants were estimated for both
      chemical and biological degradations. The data show that prechemical oxidations
      facilitated removal of total petroleum hydrocarbons (TPH) (up to 80%) within
      shorter times (<50 days) than biological alone. KMnO4 and H202 were better
      oxidants in terms of mass reduction in shorter times yet to some extent inhibited
      the subsequent microbial activity. MgO2 was a moderate oxidant with less
      inhibition of microbial activity. Selective degradation of the EC fractions was
      observed for both chemical and biological processes. The biological processes
      were much less effective than the prechemical oxidations in transforming aromatic
      fractions, the more toxic fractions. The favorable substrates (i.e., aliphatic EC
      approximately 10) for microbial growth were also those most subject to chemical
      oxidation. The results suggest that for remediation of petroleum contaminants,
      sequential chemical and biological technologies may surpass biological alone and
      more moderate oxidants such as MgO2 may be better candidates. More work is needed
      on the optimal dose and residence time for applied oxidants and on the
      application to engineering design and formulation of cleanup standards.

PMID- 14594389
TI  - On-line analysis of the size distribution of fine and ultrafine aerosol particles
      in flue and stack gas of a municipal waste incineration plant: effects of dynamic
      process control measures and emission reduction devices.
AB  - The size distribution of particles in the waste gas of a municipal waste
      incineration plant (23 MW) was measured on-line at two sampling points in the
      flue-gas duct (700 and 300 degrees C) as well as in the stack gas (80 degrees C).
      The measurements were performed during both stable combustion conditions and
      transient operating conditions. The particle measurements were carried out by a
      mobile system consisting of a home-designed sampling system with dilution device
      and a scanning mobility particle sizer (SMPS) for the particle size range 17-600
      nm as well as an aerodynamic particle sizer (APS) for the size range 500 nm-30
      microm. The APS and SMPS data were combined using a special method and a home
      written software tool. The maximum of the particle-size distribution in the flue
      gas of the incinerator shifts from about 90 nm at the 700 degrees C sampling
      point to about 140 nm at the 300 degrees C point, showing the particle growth by
      coagulation processes and condensation of inorganic and organic gaseous species
      with decreasing temperature. This finding is consistent with the measured
      concentration profiles of gaseous organic chemical species in the flue gas. While
      at flue-gas temperatures of 600-800 degrees C a rich pattern of polycyclic
      aromatic hydrocarbon species (PAH) is observable, the PAH concentrations are
      considerably reduced further downstream of the flue-gas channel, where the
      temperature drops below 500 degrees C. Condensation and reactive bonding of
      gaseous chemicals onto particulate matter is, among other reasons, responsible
      for the depletion of gas-phase species. Process control measures, such as firing
      the backup burners or cleaning of the grate with pressurized air, can cause
      dynamic changes of the particle-size distribution. Furthermore the flue-gas
      cleaning measures have great impact onto both the particle concentration and the
      size distribution. For this reason the impact of one particular emission
      reduction device, the wet electrostatic dust precipitator (wet-ESP), is
      evaluated. The wet-ESP reduces considerably the particle concentration over the
      whole size range. Behind the flue-gas processing units a broad maximum in the
      particle-size distribution occurs at about 70 nm, but no pronounced particle-size
      distribution could be observed. The particle concentration level atthis maximum
      is about 3 magnitudes lower than in the raw flue gas. However, intermittent
      periods lasting for several minutes of high emissions of ultrafine particles with
      d < 40 nm were observed. These particles are most likely formed by nucleation
      processes behind the wet-ESP from gas-phase constituents of the stack gas.

PMID- 14594390
TI  - Influences of water vapor on Cr(VI) reduction by gaseous hydrogen sulfide.
AB  - In Situ Gaseous Reduction (ISGR) using hydrogen sulfide (H2S) is a technology
      developed for soil remediation by reductive immobilization of contaminants such
      as hexavalent chromium (Cr(VI)). Deploying the technology requires us to obtain a
      much-improved understanding of the interactions among the contaminants, H2S, and
      various soil components. In this study, Cr(VI) reduction by gaseous H2S was
      examined under various relative humidities (0-96.7%), concentrations of Cr(VI)
      (127-475 microg/g of solid), and H2S (0-800 ppm(v)) and by using Cr(VI) compounds
      with different solubilities. Glass beads with various average diameters (GA =
      0.600 mm; GB = 0.212-0.300 mm; and GC = 0.106 mm) and silica (SA = 0.075-0.150
      mm) were used as matrices to support K2CrO4, CaCrO4, PbCrO4, or BaCrO4, and
      reduction of these compounds by gaseous H2S was monitored by Cr(VI) analysis
      following extractions with distilled water or hot alkali solution. The results
      showed that Cr(VI) reduction relied on both the relative humidity of the gaseous
      stream and the size of particles onto which Cr(VI) was deposited. The relative
      humidity required for fast Cr(VI) reduction was 85% for GA, 61% for GB, 6% for
      SA, and 0% for GC. It was believed that a water film formed on the particle
      surfaces under appropriate humidity conditions, resulting in Cr(VI) compound
      dissolution and subsequent reduction. For nonsoluble Cr(VI) compounds including
      PbCrO4 and BaCrO4, no reduction by H2S was observed, even at high relative
      humidity (96.7%), due to lack of dissolution. This study indicated that ISGR
      treatment in soils requires appropriate moisture content in the subsurface or
      maintaining a suitable humidity in the treatment gas stream to maximize chromium
      immobilization.

PMID- 14594391
TI  - Leaching of lead from computer printed wire boards and cathode ray tubes by
      municipal solid waste landfill leachates.
AB  - The proper management of discarded electronic devices (E-waste) is an important
      issue for solid waste professionals because of the magnitude of the waste stream
      and because these devices often contain a variety of toxic metals (e.g., lead).
      While recycling of E-waste is developing, much of this waste stream is disposed
      in landfills. Leaching tests are frequently used to characterize the potential of
      a solid waste to leach when disposed in a landfill. In the United States, the
      Toxicity Characteristic Leaching Procedure (TCLP) is used to determine whether a
      solid waste is a hazardous waste by the toxicity characteristic. The TCLP is
      designed to simulate worse-case leaching in a landfill environment where the
      waste is co-disposed with municipal solid waste (MSW). While the TCLP is a
      required analysis from a regulatory perspective, the leachate concentrations
      measured may not accurately reflect the concentrations observed under typical
      landfill conditions. Another method that can be performed to assess the degree a
      pollutant might leach from a waste in a landfill is to use actual landfill
      leachate as the leaching solution. In this study, two lead-containing components
      found in electronic devices (printed wire boards from computers and cathode ray
      tubes from computers and televisions) were leached using the TCLP and leachates
      from 11 Florida landfills. California's Waste Extraction Test (WET) and the
      Synthetic Precipitation Leaching Procedure were also performed. The results
      indicated that the extractions using MSW landfill leachates resulted in lower
      lead concentrations than those by the TCLP. The pH of the leaching solution and
      the ability of the organic acids in the TCLP and WET to complex with the lead are
      factors that regulate the amount of lead leached.

PMID- 14594392
TI  - Bactericidal activity of copper-deposited TiO2 thin film under weak UV light
      illumination.
AB  - The bactericidal activity of copper-deposited titanium dioxide thin film
      (Cu/TiO2) was investigated under very weak ultraviolet (UV) light illumination.
      To elucidate the roles of the film photocatalyst and the deposited copper in the
      bactericidal activity, cells from a copper-resistant Escherichia coli (E. coli)
      strain were utilized. A decrease in survival rate was not observed with the
      copper-resistant cells under dark conditions, but when illuminated with a very
      weak UV intensity of 1 microW/cm2, the survival rate decreased, suggesting
      photocatalytic bactericidal activity. The decay curve of survival on the Cu/TiO2
      film under very weak UV light illumination consisted of two steps, similar to the
      survival change of normal E. coli on TiO2 films under rather strong UV
      illumination. The first step is due to the partial decomposition of the outer
      membrane in the cell envelope by a photocatalytic process, followed by permeation
      of the copper ions into the cytoplasmic membrane. The second step is due to a
      disorder of the cytoplasmic membrane caused by the copper ions, which results in
      a loss of the cell's integrity. These processes explain why the Cu/TiO2 film
      system shows an effective bactericidal activity even under very weak UV light
      illumination.

PMID- 14594393
TI  - Degradation of organic contaminants in water with sulfate radicals generated by
      the conjunction of peroxymonosulfate with cobalt.
AB  - A highly efficient advanced oxidation process for the destruction of organic
      contaminants in water is reported. The technology is based on the cobalt-mediated
      decomposition of peroxymonosulfate that leads to the formation of very strong
      oxidizing species (sulfate radicals) in the aqueous phase. The system is a
      modification of the Fenton Reagent, since an oxidant is coupled with a transition
      metal in a similar manner. Sulfate radicals were identified with quenching
      studies using specific alcohols. The study was primarily focused on comparing the
      cobalt/peroxymonosulfate (Co/PMS) reagent with the traditional Fenton Reagent
      [Fe(II)/H2O2] in the dark, at the pH range 2.0-9.0 with and without the presence
      of buffers such as phosphate and carbonate. Three model contaminants that show
      diversity in structure were tested: 2,4-dichlorophenol, atrazine, and
      naphthalene. Cobalt/peroxymonosulfate was consistently proven to be more
      efficient than the Fenton Reagent for the degradation of 2,4-dichlorophenol and
      atrazine, at all the conditions tested. At high pH values, where the efficiency
      of the Fenton Reagent was diminished, the reactivity of the Co/PMS system was
      sustained at high values. When naphthalene was treated with the two oxidizing
      systems in comparison, the Fenton Reagent demonstrated higher degradation
      efficiencies than cobalt/peroxymonosulfate at acidic pH, but, at higher pH
      (neutral), the latter was proven much more effective. The extent of
      mineralization, as total organic carbon removed,was also monitored, and again the
      Co/PMS reagent demonstrated higher efficiencies than the Fenton Reagent. Cobalt
      showed true catalytic activity in the overall process, since extremely low
      concentrations (in the range of microg/L) were sufficient for the decomposition
      of the oxidant and thus the radical generation. The advantage of Co/PMS compared
      to the traditional Fenton Reagent is attributed primarily to the oxidizing
      strength of the radicals formed, since sulfate radicals are stronger oxidants
      than hydroxyl and the thermodynamics of the transition-metal-oxidant coupling.

PMID- 14594394
TI  - Photochemistry of 4-chlorophenol on cellulose and silica.
AB  - The photochemistry of 4-chlorophenol (4-CP) was studied on silica and cellulose,
      using time-resolved diffuse reflectance techniques and product degradation
      analysis. The results have shown that the photochemistry of 4-CP depends on the
      support, on the concentration, and also on the sample preparation method.
      Transient absorption and photoproduct results can be understood by assuming the
      formation of the carbene 4-oxocyclohexa-2,5-dienylidene in both supports. On
      cellulose, at concentrations lower than 10 micromol g(-1), the carbene leads to
      the unsubstituted phenoxyl radical, and phenol is the main degradation product.
      At higher concentrations a new transient resulting from phenoxyl radicals
      coupling was also observed, and dihydroxybiphenyls are also formed. The reaction
      of the carbene with ground-state 4-CP was also detected through the formation of
      5-chloro-2,4'-dihydroxybiphenyl. 4-Chlorophenoxyl radical and degradations
      products resulting from its coupling were also detected. Oxygen has little effect
      on the photochemistry of 4-CP on cellulose. On silica the transient benzoquinone
      O-oxide was formed in the presence of oxygen. Benzoquinone and hydroquinone are
      the main degradation products. In well-dried samples the formation of
      hydroquinone is reduced. At higher concentrations the same products as detected
      on cellulose were observed. 4-CP undergoes slow photochemical decomposition under
      solar radiation in both supports. The same main degradation products were
      observed in these conditions.

PMID- 14594395
TI  - Treatment of methyl tert-butyl ether contaminated water using a dense medium
      plasma reactor: a mechanistic and kinetic investigation.
AB  - Plasma treatment of contaminated water appears to be a promising alternative for
      the oxidation of aqueous organic pollutants. This study examines the kinetic and
      oxidation mechanisms of methyl tert-butyl ether (MTBE) in a dense medium plasma
      (DMP) reactor utilizing gas chromatography-mass spectrometry and gas
      chromatography-thermal conductivity techniques. A rate law is developed for the
      removal of MTBE from an aqueous solution in the DMP reactor. Rate constants are
      also derived for three reactor configurations and two pin array spin rates. The
      oxidation products from the treatment of MTBE-contaminated water in the DMP
      reactor were found to be predominately carbon dioxide, with smaller amounts of
      acetone, tert-butyl formate, and formaldehyde. The lack of stable intermediate
      products suggests that the MTBE is, to some extent, oxidized directly to carbon
      dioxide, making the DMP reactor a promising tool in the future remediation of
      water. Chemical and physical mechanisms together with carbon balances are used to
      describe the formation of the oxidation products and the important aspects of the
      plasma discharge.

PMID- 14594396
TI  - Highly dispersed green silicate and oxide pigments precipitated from model
      systems of postgalvanic waste.
AB  - A procedure was worked out to obtain highly dispersed green silicate and oxide
      pigments precipitated from postgalvanic waste. The highly dispersed chromium(III)
      silicates and oxides were produced from the waste, originating from chromium
      plating, by reduction of Cr(VI) to Cr(III) employing various reducing agents. All
      the reductions were conducted in an acidic medium. Solutions of Cr(III), obtained
      in reducing processes, were employed to precipitate silicate pigments (using
      sodium metasilicate solution and containing mainly chromium(III) silicates) and
      oxide pigments (using sodium hydroxide and containing chromium(III) oxides). The
      precipitated silicates and oxides were subjected to a comprehensive
      physicochemical analysis (estimating bulk density, capacities to absorb water,
      dibutyl phthalate, paraffin oil, particle size distribution, and morphology of
      particle surface). Precipitation process (its parameters) and heating of the
      reactive mixture exerts a significant effect on the principal physicochemical
      properties of the pigments. The heating significantly affects first of all color
      shade of the obtained silicate and oxide pigments as well as their dispersion.
      Coprecipitated chromium(III) and iron(III) silicates exhibit a brownish color and
      a reasonably uniform character. Apart from primary agglomerates (in the range of
      414-717 nm), they contain small amounts of secondary agglomerates (in the range
      of 4154-6445 nm). Best physicochemical parameters have been demonstrated by
      chromium pigments which have been precipitated from chromium solutions reduced
      using hydrogen peroxide. Chromium(III) oxides deserve particular distinction
      since their structure includes primary particles, primary agglomerates but is
      completely free of secondary agglomerates. The pigments manifest a brightly green
      color and a low capacity to absorb water (100 cm3 x 100 g(-1)). Application of
      hydrophobicity-inducing agents in the course of precipitation has corrected
      physicochemical parameters of both the oxides and silicates of chromium(II).
      Their bulk densities have been clearly decreased (to as low as below 250 g x L(
      1) in the case of chromium(III) silicate), while capacities to absorb paraffin
      oil have increased to as much as 750 cm3 x 100 g(-1) for chromium(II) oxide. The
      respective particle size distribution has shown a tendency for disappearance of
      large accumulations of secondary agglomerates.

PMID- 14594397
TI  - Comment on "Estrogen receptor agonist fate during wastewater and biosolids
      treatment processes: a mass balance analysis".

PMID- 14594398
TI  - Comment on "Fuels for urban transit buses: a cost-effectiveness analysis".

PMID- 14594399
TI  - Antimicrobial resistance of Listeria monocytogenes.
AB  - Listeria monocytogenes is an opportunistic pathogen that causes rare but
      frequently fatal infections, termed listerioses. In general, strains of L.
      monocytogenes are susceptible to a wide range of antibiotics, except for the
      cephalosporins, fluorochinolones and fosfomycin (Hof, 1991). The current therapy
      of choice is a combination of ampicillin and aminoglycoside, usually gentamicin
      (Lorber, 1997). In cases when it is not possible to use a beta-lactam antibiotic,
      second-choice therapy involves the use of an association of trimethoprim with a
      sulfonamide, such as in co-trimoxazole, in which the more active in the
      combination seems trimethoprim, synergized by the sulfa compound. Other second
      line agents for listeriosis include erythromycin and vancomycin (Temple and
      Nahata, 2000). The first strains of L. monocytogenes resistant to antibiotics
      were reported in 1988 (Poyart-Salmeron et al. 1990) The present paper reviews the
      current state of affairs with regard to the resistance of L. monocytogenes
      isolated from food products and clinical material to different antibiotics, with
      particular emphasis on those used in the therapy of listeriosis.

PMID- 14594400
TI  - Ampicillin resistance in Listeria monocytogenes acquired as a result of
      transposon mutagenesis.
AB  - We have used plasmid pLTV3, which carries transposon Tn917, to obtain a series of
      mutants of Listeria monocytogenes EGD showing varied degrees of resistance to
      ampicillin and other beta-lactam antibiotics, including imipenem. In this paper
      we focus on the characteristics of two strains in which decreased susceptibility
      to ampicillin is accompanied by changes in the structure of the cell wall murein
      and cell-wall related changes of phenotype.

PMID- 14594401
TI  - Antibiotic susceptibility patterns of respiratory isolates of Staphylococcus
      aureus in a Turkish university hospital.
AB  - A total of 391 respiratory isolates of Staphylococcus aureus in Sivas (Turkey)
      were studied between January 1999-2002. The organisms were cultured from the
      following specimens: throat (43%), sputum (28%), transtracheal/endotracheal
      aspirates (27%), and bronchial lavage (2%). The isolates were tested against 11
      different antibiotics by a disk diffusion method or standardized microdilution
      technique. Methicillin-resistant isolates constituted 76.9% of all isolates. Most
      of the methicillin-resistant isolates (95.1%) were isolated from inpatients. The
      rate of methicillin-resistant isolates in throat, sputum, and tracheal aspirates
      was 17.2%, 60.1%, and 68.9%, respectively. The resistance of methicillin
      resistant isolates in throat to teicoplanin was 3.4%. The methicillin-sensitive
      isolates were susceptible to most agents tested, while most methicillin-resistant
      isolates were resistant to these agents. Overall resistance to erythromycin was
      61.9%, tetracycline 56.6%, gentamicin 50.7%, ofloxacin 42.0%, rifampin 40.8%,
      clindamycin 38.9%, chloramphenicol 19.0%, co-trimoxazole 10.2%, and vancomycin
      0%.

PMID- 14594402
TI  - Phenotypic and molecular characteristics of typical and atypical Escherichia coli
      O157, clinical and food isolates.
AB  - Enrichment, colony isolation and confirmation are three general phases of a
      standard diagnostic method. E. coli O 157 (the main member of EHEC group) differs
      metabolically from other strains of E. coli in a number of ways. Most isolates
      are slow- or non-fermenters of sorbitol and lack the enzyme beta-glucuronidase
      (GUD). But, a variety of atypical strains of E. coli O157 (sorbitol-fermenting
      variants, nonmotile and GUD-positive) have been reported. The discovery of these
      atypical pathogenic strains brings into question the validity of testing for the
      pathogen only by biotyping. Using classical cultivation and immunomagnetic
      separation, we have isolated from food a few atypical E. coli O157 (sorbitol
      fermenting strains, GUD positive, nonmotile O157 strain which does not
      agglutinate with O157 latex and does not produce Shiga toxin). On the other hand,
      non-O157 VTEC (O26 serotype) producing Shiga toxin was isolated from meat.
      Molecular markers of E. coli O157 and virulence-associated factors of strains
      with aberrant biochemical properties were studied by PCR. This method helped us
      in the final identification of isolates. Since it was suggested that the
      production of verotoxins (VT) is accompanied by the production of enterohemolysin
      (Ehly) such correlation has also been evaluated in respect to the collection of
      VTEC of human, animal and food origin.

PMID- 14594403
TI  - Purification and characterization of xylanase from a thermophilic Streptomyces
      sp. K37.
AB  - Extracellular xylanase (EC 3.2.1.8) from Streptomyces sp. K37 was purified 33.53
      by ultrafiltration and cation exchange chromatography followed by gel filtration
      chromatography. The optimum pH and temperature for purified xylanase were found
      to be pH 6.0 and 60 degrees C. The Km and V(max) values of the purified xylanase
      were 15.4 mg ml(-1) and 0.67 micromole reducing sugar min(-1) ml(-1). High
      performance liquid chromatography (HPLC) gel filtration of the purified xylanase
      eluted xylanase activity as a peak corresponding to the molecular weight of about
      24.3 kDa while the molecular weight determined by SDS-PAGE was found to be 26.4
      kDa. The purified xylanase of Streptomyces sp. K37 was found to be endoxylanase
      and non arabinose liberating enzyme and was highly glycosylated (73.97%).

PMID- 14594404
TI  - Relationship between soil microbial diversity and bioremediation process at an
      oil refinery.
AB  - Microbial diversity in hydrocarbon-contaminated soil was characterized during a
      bioremediation project at an oil refinery. The project consisted of isolation and
      cultivation of microbes on laboratory media and the subsequent characterization
      of pure isolates. In a lagoon at the Czechowice Oil Refinery, Poland, a biopile
      with actively and passively aerated sections was constructed and has been
      operated since 1997. The bioremediation process has been continuously monitored
      by physical, chemical, and microbiological methods. One hundred and forty nine
      bacterial and fungal strains were isolated from site soils by standard
      procedures. Analysis of cultivable microorganisms revealed a diverse microbial
      population within the cultured isolates. Among isolated strains, Pseudomonas and
      Chryseomonas genera predominated in the bacterial population while Candida,
      Fusarium, and Trichophyton dominated the fungal population. This paper describes
      the application of traditional microbiological methods (plating and microscopic
      methods) to evaluate cultivable microbial diversity in bioremediated soil.

PMID- 14594405
TI  - The molecular characterisation of the extended spectrum beta-lactamase (ESBL)
      producing strain of Salmonella enterica serovar Mbandaka isolated in Poland.
AB  - The molecular attributes of the first ESBL producing isolate 267/99 of Salmonella
      enterica serovar Mbandaka isolated in 1999 in Poland were characterised. Tested
      strain produced CTX-M-3 and TEM-1 beta-lactamases, encoded by genes localised on
      the about 80 kb self-transferable plasmid, harbouring the 2 kb class 1 integron
      carrying aadA2 gene.

PMID- 14594407
TI  - Increased synthesis of dihydroxybenzoic acid in the presence of aluminum by
      Rhizobium MO1.
AB  - Rhizobizum sp. MO1, a mung bean (Vigna radiata) symbiont, produces a catecholate
      type of siderophore, 2,3-dihydroxy benzoic acid (DHBA), in iron depleted medium.
      Addition of aluminum to the medium decreased the growth but increased the
      production of the siderophore.

PMID- 14594406
TI  - Association of EBV infection with lymphomas.
AB  - The diagnostic reliability of the IgA immunoblot test in the diagnosis of EBV
      associated lymphomas was examined. Serum samples from patients with clinically
      diagnosed lymphomas were tested for the presence of EBV specific IgG and IgA
      antibodies and based on test results the EBV association with lymphoma was
      estimated. Obtained results indicated that EBV IgA testing may be helpful in
      diagnosis of EBV association with lymphomas.

PMID- 14594408
TI  - Influence of air-ions on selected microorganisms.
AB  - In the following work the influence of air-ions and ozone on the selected
      microorganisms, first of all on Staphylococcus epidermidis is discussed. Carried
      out investigations proved that the levels of air-ions concentrations, causing
      specific changes in the development of particular microorganisms, are very
      differentiated and depend on individual parameters of those organisms. These
      levels are generally characterized by high values of concentrations, range n +/-
      =4 x 10(6) ions/cm3 and are connected with the type of the air-ions used. However
      investigations did not confirm any negative influence of the positive air-ions
      seen as a destructive factor upon any of the investigated microorganisms.

PMID- 14594409
TI  - Atorvastatin reduced coronary and stroke events in patients with hypertension and
      without dyslipidemia.

PMID- 14594410
TI  - Review: low-molecular-weight heparin is effective and safe in the acute coronary
      syndromes.

PMID- 14594411
TI  - A 10-mg nomogram was more effective than a 5-mg nomogram for warfarin induction
      in outpatient venous thromboembolism.

PMID- 14594412
TI  - Estrogen plus progestin did not improve health-related quality of life in
      postmenopausal women 50 to 79 years of age.

PMID- 14594413
TI  - Estrogen plus progestin increased risk for breast cancer in postmenopausal women.

PMID- 14594414
TI  - Estrogen plus progestin increased risk for stroke and probable dementia in
      postmenopausal women.

PMID- 14594415
TI  - Tiotropium reduced exacerbations and health resource use in COPD.

PMID- 14594418
TI  - Review: rosiglitazone or pioglitazone as add-on therapy is effective for glycemic
      control in type 2 diabetes.

PMID- 14594416
TI  - A disease-specific self-management program reduced hospital utilization and
      improved health status in COPD.

PMID- 14594417
TI  - Therapy guided by pulmonary-artery catheter for high-risk surgical patients was
      not better than standard care.

PMID- 14594419
TI  - Enalapril reduced the risk for developing new-onset diabetes in left ventricular
      dysfunction.

PMID- 14594420
TI  - A counseling strategy was better than usual care for adopting and maintaining
      physical activity in type 2 diabetes.

PMID- 14594421
TI  - Review: evidence is inconclusive about the role of lower-carbohydrate diets in
      weight loss in the outpatient setting.

PMID- 14594422
TI  - Lifestyle recommendations reduced blood pressure in patients with above-optimal
      blood pressure.

PMID- 14594424
TI  - Aspirin prevented new colorectal adenomas in patients with previous colorectal
      cancer.

PMID- 14594423
TI  - Chemoprophylaxis with aspirin (81 mg daily) reduced the incidence of colorectal
      adenomas in persons at risk.

PMID- 14594425
TI  - Controlled-onset extended-release verapamil was not equivalent to standard
      therapy for preventing cardiovascular disease.

PMID- 14594426
TI  - Both endurance training and strength training reduced disability and pain in
      chronic nonspecific neck pain in women.

PMID- 14594427
TI  - Review: drugs do not improve symptoms in urinary urge incontinence and may have
      side effects.

PMID- 14594428
TI  - Pacemaker therapy did not reduce recurrent vasovagal syncope.

PMID- 14594429
TI  - Combining fasting plasma glucose and glycosylated hemoglobin improved the
      accuracy for detecting patients with diabetes.

PMID- 14594430
TI  - Conventional cervical smears were better than monolayer cytology or human
      papillomavirus testing for detecting cervical cancer.

PMID- 14594431
TI  - Review: delirium predicts 12-month mortality independent of dementia status.

PMID- 14594432
TI  - Review: depression, social isolation, and certain life events are associated with
      the development of coronary heart disease.

PMID- 14594433
TI  - Evidence-based decision making--the 6-step approach.

PMID- 14594434
TI  - Practice corner: setting EBM in motion.

PMID- 14594435
TI  - Amlodipine or lisinopril was not better than chlorthalidone in lowering CHD risk
      in hypertension.

PMID- 14594436
TI  - Costs and cost effectiveness of low molecular weight heparins and platelet
      glycoprotein IIb/IIIa inhibitors: in the management of acute coronary syndromes.
AB  - The most well established antithrombotic treatment for acute coronary syndromes
      (ACS) is unfractionated heparin (UFH) plus aspirin, but such treatment may not
      prevent arterial thrombotic events. Low molecular weight heparins (LMWHs) and
      platelet glycoprotein (GP) IIb/IIIa inhibitors offer alternative or adjunctive
      treatments. However, before these alternatives with higher acquisition costs are
      accepted in today's healthcare systems, their cost effectiveness must be proven.
      This paper reviews international pharmacoeconomic studies on the use of LMWHs and
      GP IIb/IIIa inhibitors in patients with ACS in an attempt to determine whether
      these therapies are cost effective. Most of the studies on LMWHs have been cost
      minimisation analyses and have focused on enoxaparin sodium, because this is the
      only LMWH proven to be superior to UFH. Several analyses show that, compared with
      UFH plus aspirin, enoxaparin sodium provides cost savings both during
      hospitalisation (30 days) and 1-year follow-up. These cost savings are mainly
      attributable to fewer cardiac interventions, shorter hospital stays and lower
      administrative costs. Indeed, the clinical and economic advantages of enoxaparin
      sodium have led to its recommendation in recent guidelines as the antithrombotic
      agent of choice for coronary artery disease. Most of the economic analyses of GP
      IIb/IIIa inhibitors have been cost-effectiveness analyses. Such analyses indicate
      that the high acquisition costs of these drugs may be at least partially offset
      by reductions in other costs if a noninvasive approach to risk stratification is
      used. Furthermore, use of GP IIb/IIIa inhibitors appears to give favourable cost
      effectiveness ratios compared with other accepted therapies, such as fibrin
      specific thrombolytic therapy, in the cardiovascular field, particularly in high
      risk patients and those undergoing percutaneous coronary intervention. However,
      more comprehensive economic data on the GP IIb/IIIa inhibitors are needed.

PMID- 14594437
TI  - Cost-utility analysis of survival with epoetin-alfa versus placebo in stage IV
      breast cancer.
AB  - BACKGROUND: In a multinational trial of anaemic patients with cancer receiving
      nonplatinum-containing chemotherapy, epoetin-alfa effectively increased
      haemoglobin levels, reduced red blood cell transfusion requirements, and improved
      QOL. Although the study was not designed or powered to evaluate survival, a
      survival trend was noted favouring epoetin-alfa compared with placebo (median
      survival 17 vs 11 months [p = 0.126]). OBJECTIVES: To determine the incremental
      cost utility of epoetin-alfa versus placebo in anaemic patients with stage IV
      breast cancer from a UK National Health Service perspective. METHODS: Patient
      data regarding transfusions, epoetin-alfa usage, chemotherapy treatment cycles,
      and adverse events were recorded, with survival follow-up for 12-36 months post
      study. Stage IV breast cancer therapy costs were collected by surveying UK
      oncologists, and utilities for associated health states were from published
      sources. Costs were in British pounds and year 2000 values. Costs and benefits
      were jointly determined for the stage IV breast cancer subgroup (n = 55).
      Incremental cost-utility ratios (ICURs) were calculated assuming a 6% annual
      discount rate for costs and a 1.5% annual discount rate for benefits. Bootstrap
      simulations (10,000 iterations) were conducted to account for uncertainty, and
      sensitivity analyses were conducted to establish robustness. RESULTS: The ICUR
      for epoetin-alfa treatment was pounds 8,851 per QALY, with a 99% probability of a
      positive net benefit in QALYs (net benefit = 0.4805 years of perfect life) and a
      94% probability of being acceptable using a threshold ICUR of pounds 30,000/QALY.
      The main cost drivers distinguishing epoetin-alfa from placebo were the costs of
      drug and patient care due to increased survival. CONCLUSIONS: The available data
      suggest a high probability of favourable cost-utility outcomes with epoetin-alfa
      treatment for anaemia in patients with stage IV breast cancer receiving
      nonplatinum-containing chemotherapy. Additional studies are warranted.

PMID- 14594438
TI  - The cost effectiveness of Apligraf treatment of diabetic foot ulcers.
AB  - BACKGROUND: Diabetic foot ulcers (DFUs) present a treatment challenge and result
      in a large economic burden, requiring careful evaluation of the clinical efficacy
      and cost effectiveness of new treatment modalities. DFU clinical trials of the
      bio-engineered skin substitute Apligraf (Novartis Pharma AG, Basel, Switzerland)
      have demonstrated improved clinical efficacy compared with good wound care (GWC)
      alone. OBJECTIVE: To determine the economic impact and cost effectiveness of
      Apligraf plus GWC compared with GWC alone in the treatment of DFUs. STUDY
      PERSPECTIVE: Societal. METHODS: A Markov-based simulation model was created to
      compare the costs and effects of Apligraf plus GWC to those of GWC alone over a
      12-month period. The primary health states were 'uninfected ulcer', 'infected
      ulcer', 'gangrene', and 'healed ulcer'. Transition probabilities were based on
      clinical trial results, while cost estimates were based on estimates of resource
      utilisation in the Netherlands. The cost-effectiveness outcome measures were the
      incremental cost per ulcer-free month gained and the incremental cost per
      amputation avoided. RESULTS: Costs in the first year of treatment were Euro 4656
      for Apligraf plus GWC and Euro 5310 for GWC alone (1999 values). Treatment with
      Apligraf led to lower costs since its greater effectiveness offset the added cost
      of the product. This benefit was realised after 5 months, the crossover point of
      the two cost curves. Apligraf use increased the amount of ulcer-free time by by
      1.53 months (7.78 vs 6.25) and reduced the risk of amputation (6.3% vs 17.1%).
      Sensitivity analyses showed that cost parameters (e.g. units of Apligraf
      required, cost of treatment practice) and transition probabilities between health
      states affected the cost results. CONCLUSIONS: Treatment with Apligraf plus GWC
      resulted in a 12% reduction in costs over the first year of treatment compared
      with GWC alone. The increased ulcer-free time coupled with a reduced risk of
      amputation to a large extent offset the initial costs of the product.

PMID- 14594440
TI  - Pharmaceutical expenditure and therapeutic value of new medicines in Spain.

PMID- 14594439
TI  - Escitalopram: a pharmacoeconomic review of its use in depression.
AB  - Escitalopram (Cipralex), a new highly selective serotonin reuptake inhibitor
      (SSRI), is the active S-enantiomer of RS-citalopram. It is effective in the
      treatment of patients with major depressive disorder (MDD) and may have a faster
      onset of therapeutic effect than citalopram. It has also been shown to lead to
      improvements in measures of QOL. Escitalopram is generally well tolerated, with
      nausea being the most common adverse event associated with its use. Modelled
      pharmacoeconomic analyses found escitalopram to have a cost-effectiveness and
      cost-utility advantage over other SSRIs, including generic citalopram and
      fluoxetine and branded sertraline, and also over the serotonin-noradrenaline
      reuptake inhibitor (SNRI) venlafaxine extended-release (XR). These studies used a
      decision-analytic approach with a 6-month time horizon and were performed in
      Western Europe (year of costing 2000 or 2001). Cost-effectiveness ratios for
      escitalopram, in terms of cost per successfully treated patient over 6 months,
      ranged from Euro 871 to Euro 2598 in different countries, based on direct costs
      and remission rates, and were consistently lower (i.e. more favourable) than the
      ratios for comparators (Euro 970 to Euro 3472). Outcomes similarly favoured
      escitalopram when indirect costs (represented by those associated with sick leave
      and loss of productivity) were included. The results of comparisons with
      citalopram, fluoxetine and sertraline were not markedly affected by changes to
      assumptions in sensitivity analyses, although comparisons with venlafaxine XR
      were sensitive to changes in the remission rate. The mean number of QALYs gained
      during the 6-month period was similar for all drugs evaluated, but direct costs
      were lower with escitalopram, leading to lower cost-utility ratios than for
      comparators. Incremental analyses performed in two of the studies confirmed the
      cost-effectiveness and cost-utility advantage of escitalopram. A prospective, 8
      week comparative pharmacoeconomic analysis found that escitalopram achieved
      similar efficacy to venlafaxine XR, but was associated with 40% lower direct
      costs (Euro 85 vs Euro 142 per patient over 8 weeks; 2001 costs), although this
      difference did not reach statistical significance. In both the modelled and
      prospective analyses, the differences in overall direct costs were mainly due to
      lower secondary care costs (in particular those related to hospitalisation) with
      escitalopram. In the prospective analysis, escitalopram had lower estimated drug
      acquisition costs than venlafaxine XR. CONCLUSION: Escitalopram, the S-enantiomer
      of RS-citalopram and a highly selective SSRI, is an effective antidepressant in
      patients with MDD, has a favourable tolerability profile, and, on the basis of
      available data, appears to have a rapid onset of therapeutic effect. Modelled
      pharmacoeconomic analyses from Western Europe suggest that it may be a cost
      effective alternative to generic citalopram, generic fluoxetine and sertraline.
      Although the available data are less conclusive in comparison with venlafaxine
      XR, escitalopram is at least as cost effective as the SNRI based on a prospective
      study, and potentially more cost effective based on modelled analyses. Overall,
      clinical and pharmacoeconomic data support the use of escitalopram as first-line
      therapy in patients with MDD.

PMID- 14594441
TI  - Can the time window for administration of thrombolytics in stroke be increased?
AB  - Level 1 evidence now shows that thrombolysis in cases of acute ischaemic stroke
      is effective if administered within 3 hours of stroke onset. This benefit has
      been shown to be time dependent and potentially extends beyond 3 hours, with
      evidence that potentially viable penumbral tissue may be present in a significant
      proportion of cases well beyond 3-6 hours and, in isolated cases, perhaps up to
      48 hours. This exposes a "stroke recovery gap", the difference observed between
      the clinical response to thrombolytic therapy in a given population of patients
      presenting with ischaemic stroke and the potential clinical recovery if all of
      the penumbra were salvaged under ideal circumstances. The means of bridging this
      "stroke recovery gap" using thrombolysis must involve extending the therapeutic
      time window (i.e. the time between stroke onset and administration of
      thrombolytics). Approaches to do this include the use of: (i) improved patient
      selection with modern neuroimaging techniques, particularly magnetic resonance
      imaging using perfusion-weighted image/diffusion-weighted image mismatch; (ii)
      newer thrombolytic agents; (iii) lower doses of these agents; (iv) varied methods
      of administration of thrombolytic therapy including combined intravenous and
      intra-arterial approaches; and (v) adjunctive therapies such as neuroprotectants.
      Should these means of extending the time window for thrombolysis prove
      successful, a more widespread use of this form of acute stroke therapy will be
      possible.

PMID- 14594444
TI  - The cost-benefit of cholinesterase inhibitors in mild to moderate dementia: a
      willingness-to-pay approach.
AB  - OBJECTIVE: This study aimed to measure the economic value of cholinesterase
      inhibitors when used to treat Alzheimer's disease using the willingness-to-pay
      (WTP) approach and the framework of cost-benefit analysis. METHODS AND STUDY
      DESIGN: A cost-benefit analysis using the WTP approach was employed. The study
      sample consisted of 28 nonprofessional caregivers of outpatients with mild to
      moderate dementia from Toronto, ON, Canada. The caregivers were presented with
      four scenarios. In the first scenario, scenario A, a hypothetical patient with
      mild dementia was stabilised with a cholinesterase inhibitor. In the second
      scenario, scenario A with adverse effects, the above patient (A) experienced
      adverse effects caused by the drug. In the third scenario, scenario B, the
      patient exhibited behavioural symptoms in addition to mild dementia, and both
      were stabilised with the drug. In the fourth scenario, scenario B with adverse
      effects, the above patient (B) experienced adverse effects caused by the drug.
      The caregivers were then asked what amount they would pay, in Canadian dollars,
      each year to buy the medication, assuming that they were the caregivers of the
      patient described. A multivariate regression analysis was performed to assess the
      relationship between the demographic data (including the caregiver's yearly
      income) and the WTP. The average WTP was also predicted for the general
      population and the elderly population of Canada using data from Statistics
      Canada, and these values were compared with the cost of the medication. STUDY
      PERSPECTIVE: Nonprofessional caregiver perspective. All monetary values are 1999
      values unless otherwise specified. RESULTS: The mean yearly WTP was $Can4540 (95%
      CI 2334-6746) for scenario A, $Can3686 (95% CI 1530-5842) for scenario A with
      adverse effects, $Can5003 (95% CI 2661-7345) for scenario B and $Can4486 (95% CI
      2222-6750) for scenario B with adverse effects. The WTP decreased when drug
      adverse effects were present (significantly in scenario A; p = 0.04), but did not
      significantly increase when behavioural symptoms were present and stabilised. In
      all scenarios, caregiver yearly income was the only significant predictor of WTP,
      in the direction expected. For all scenarios, the calculated WTPs from the
      regression analysis using our sample mean, the average Canadian population data
      and the elderly population data were all higher than the yearly cost of the
      cholinesterase inhibitors, with the net benefit ranging from $Can1723 to
      $Can4508. CONCLUSIONS: The results of the study, from a small sample of
      nonprofessional caregivers, revealed that the caregivers are willing to pay more
      for cholinesterase inhibitors than the drugs cost, even when the adverse effects
      of the drugs are taken into consideration. This indicates a net benefit for
      cholinesterase inhibitors in the treatment of mild to moderate dementia from a
      consumer's point of view.

PMID- 14594442
TI  - Seizures in alcohol-dependent patients: epidemiology, pathophysiology and
      management.
AB  - The relationship between alcohol and seizures is complex and multifaceted. The
      prevalence of epilepsy in alcohol-dependent patients of western industrialised
      countries may be at least triple that in the general population, whereas the
      prevalence of alcoholism is only slightly higher in patients with epilepsy than
      in the general population. The seizure threshold is raised by alcohol drinking
      and declines on cessation of drinking. As a result, during withdrawal from
      alcohol, usually 6-48 hours after the cessation of drinking, seizures may occur.
      Alcohol acts on the brain through several mechanisms that influence seizure
      threshold. These include effects on calcium and chloride flux through the ion
      gated glutamate NMDA and GABA receptors. During prolonged intoxication, the CNS
      adapts to the effects of alcohol, resulting in tolerance; however, these adaptive
      effects seem to be transient, disappearing after alcohol intake is stopped.
      Although the relationship of seizures to alcohol use is likely to be dose
      dependent and causal, the available clinical data do not suggest that alcohol use
      results in seizure genesis. However, a genetic predisposition to alcohol
      withdrawal seizures is possible. Other seizures in alcohol-dependent individuals
      may be due to concurrent metabolic, toxic, infectious, traumatic, neoplastic and
      cerebrovascular diseases and are frequently partial-onset seizures. Alcohol abuse
      is a major precipitant of status epilepticus (9-25% of cases), which may even be
      the first-ever seizure type. Prompt treatment of alcohol withdrawal seizures is
      recommended to prevent status epilepticus. During the detoxification process,
      primary and secondary preventative measures can be taken. A meta-analysis of
      controlled trials for the primary prevention of alcohol withdrawal seizures
      demonstrated a highly significant risk reduction for seizures with
      benzodiazepines and antiepileptic drugs and an increased risk with
      antipsychotics. A meta-analysis of randomised, placebo-controlled trials for the
      secondary prevention of seizures after alcohol withdrawal showed lorazepam to be
      effective, whereas phenytoin was ineffective. Because withdrawal seizures do not
      recur if the patient remains abstinent, long-term administration of antiepileptic
      drugs is unnecessary in abstinent patients. The first seizure not related to
      alcohol withdrawal should not result in permanent drug treatment in an alcohol
      dependent patient, because of poor compliance and the high likelihood of
      remission. The treatment of alcohol dependence is more important and should be
      prioritised before the prevention of further seizures.

PMID- 14594443
TI  - Pharmacological management of neuropathic pain.
AB  - In health, the nervous system exists in a balance between inhibitory and
      excitatory influences. This balance may be upset if neural tissue is damaged or
      irritated and may give rise to neuropathic pain. Such neuropathic pain does not
      respond consistently to opioid analgesics or NSAIDs and it may therefore be
      necessary to utilise other therapeutic agents with known activity on either the
      excitatory or inhibitory components of the pain pathway. These other agents are
      traditionally considered with reference to their original uses; we still refer to
      tricyclic antidepressants (TCAs) and anticonvulsant drugs when a consideration of
      their modes of action may allow more rational use. For example, carbamazepine is
      related to the TCAs by virtue of its chemical structure and proposed mode of
      action and yet is still classified as an anticonvulsant drug. With respect to the
      opioids, increasing evidence points to an analgesic effect in neuropathic pain,
      although concerns regarding tolerance and dependence still prevent more
      widespread use. The anticonvulsants comprise a group of compounds possessing
      anticonvulsant and analgesic properties, but each possesses differing modes of
      action and so several members of the class should be tried before a conclusion is
      reached that they, as a whole, are ineffective. TCAs may also have a role in the
      treatment of neuropathic pain. As with all drugs, if their use is not associated
      with pain relief in a defined period of time, their use should be terminated.
      Topical TCAs may also have a role where the area of neuropathic pain is small.
      Other options, such as SSRIs, membrane stabilisers, capsaicin, baclofen and
      clonidine may have potential in treating neuropathic pain. The available evidence
      regarding the efficacy of currently available agents for the treatment of
      neuropathic pain is sparse. With the knowledge of achieving analgesia, according
      to the modes of actions of various agents it is hoped that the treatment of this
      difficult condition may be more logical and successful.

PMID- 14594446
TI  - Structural and functional dissection of a conserved destabilizing element of
      cyclo-oxygenase-2 mRNA: evidence against the involvement of AUF-1 [AU-rich
      element/poly(U)-binding/degradation factor-1], AUF-2, tristetraprolin, HuR (Hu
      antigen R) or FBP1 (far-upstream-sequence-element-binding protein 1).
AB  - COX-2 (cyclo-oxygenase-2) mRNA is degraded rapidly in resting cells, but is
      stabilized by the mitogen-activated protein kinase p38 signalling pathway in
      response to pro-inflammatory stimuli. A conserved ARE (AU-rich element) of the
      COX-2 3' untranslated region, CR1 (conserved region 1), acts as a potent
      instability determinant, and mediates stabilization in response to p38
      activation. A detailed structural and functional analysis of this element was
      performed in an attempt to identify RNA-binding proteins involved in the
      regulation of COX-2 mRNA stability. Destabilization of a beta-globin reporter
      mRNA was dependent upon two distinct AREs within CR1, each containing three
      copies of the sequence AUUUA. CR1 was shown to bind AUF-1 [ARE/poly(U)
      binding/degradation factor-1] and/or AUF-2, HuR (Hu antigen R), TTP
      (tristetraprolin) and FBP1 (far-upstream-sequence-element-binding protein 1), yet
      these factors did not appear to account for the effects of CR1 upon mRNA
      stability. Mutant sequences were identified that were incapable of destabilizing
      a reporter mRNA, yet showed unimpaired binding of FBP1 and AUF-1 and/or -2. TTP
      was absent from the HeLa cell line used in this analysis. Finally, RNA
      interference experiments argued against a prominent role for HuR in the CR1
      mediated regulation of mRNA stability. We conclude that at least one critical
      regulator of COX-2 mRNA stability is likely to remain unidentified at present.

PMID- 14594447
TI  - Ligand control of interaction in vivo between ecdysteroid receptor and
      ultraspiracle ligand-binding domain.
AB  - Ecdysteroids (Ecs) enhance the formation of Ec receptor-ultraspiracle protein
      (EcR-USP) heterodimers which regulate gene transcription. To study EcR-USP
      heterodimerization, fusion proteins were constructed from the LBDs (ligand
      binding domains) of Drosophila EcR or USP and the activation or DNA-binding
      region of GAL4 respectively. Reporter gene ( lacZ ) activation was fully
      dependent on the co-expression of the two fusion proteins and thus constitutes a
      reliable measure for the interaction in vivo between the two LBDs in the yeast
      cell. To identify structures involved in heterodimerization, a total of 27 point
      mutations were generated in the EcR and USP LBDs at selected sites.
      Heterodimerization and its inducibility by ligand were mainly affected by
      mutations in the dimerization interface and in the ligand-binding pocket of EcR
      respectively. However, also mutations not located in these structures or even in
      the LBD of USP influenced ligand-dependent heterodimerization. Together with
      previously reported ligand-binding studies, the existence of such local, intra-
      and inter-molecular mutation effects suggest that ligand-induced dimerization
      results from a synergistic interaction between ligand-binding and
      heterodimerization functions in EcR LBD, and that it depends on global features
      of the LBDs of EcR and USP and on their mutual surface compatibility.

PMID- 14594448
TI  - Latrophilin is required for toxicity of black widow spider venom in
      Caenorhabditis elegans.
AB  - Black widow spider venom (BWSV) kills Caenorhabditis elegans after injection
      owing to the presence of heat- and detergent-sensitive components, which are high
      molecular-mass latrotoxins. A C. elegans homologue of latrophilin/CIRL (calcium
      independent receptor for latrotoxin), B0457.1, was identified and shown to have
      five conserved domains. RNAi (RNA interference) of this gene rendered C. elegans
      resistant to BWSV, whereas RNAi for CYP37A1 or a neurexin I homologue, and a
      deletion mutant of the related B0286.2 gene, had no effect on BWSV toxicity. The
      latrophilin RNAi mutants exhibit changes in defaecation cycle and alterations in
      drug sensitivity. These results demonstrate that latrophilin mediates the
      toxicity of BWSV and provide evidence for a physiological function of this
      receptor.

PMID- 14594449
TI  - Human meprin alpha and beta homo-oligomers: cleavage of basement membrane
      proteins and sensitivity to metalloprotease inhibitors.
AB  - Meprin is a zinc endopeptidase of the astacin family, which is expressed as a
      membrane-bound or secreted protein in mammalian epithelial cells, in intestinal
      leucocytes and in certain cancer cells. There are two types of meprin subunits,
      alpha and beta, which form disulphide-bonded homo- and hetero-oligomers. Here we
      report on the cleavage of matrix proteins by hmeprin (human meprin) alpha and
      beta homo-oligomers, and on the interactions of these enzymes with inhibitors.
      Despite their completely different cleavage specificities, both hmeprin alpha and
      beta are able to hydrolyse basement membrane components such as collagen IV,
      nidogen-1 and fibronectin. However, they are inactive against intact collagen I.
      Hence the matrix-cleaving activity of hmeprin resembles that of gelatinases
      rather than collagenases. Hmeprin is inhibited by hydroxamic acid derivatives
      such as batimastat, galardin and Pro-Leu-Gly-hydroxamate, by TAPI-0 (tumour
      necrosis factor alpha protease inhibitor-0) and TAPI-2, and by thiol-based
      compounds such as captopril. Therapeutic targets for these inhibitors are MMPs
      (matrix metalloproteases), TACE (tumour necrosis factor alpha-converting enzyme)
      and angiotensin-converting enzyme respectively. The most effective inhibitor of
      hmeprin alpha in the present study was the naturally occurring hydroxamate
      actinonin ( K(i)=20 nM). The marked variance in the cleavage specificities of
      hmeprin alpha and beta is reflected by their interaction with the TACE inhibitor
      Ro 32-7315, whose affinity for the beta subunit (IC50=1.6 mM) is weaker by three
      orders of magnitude than that for the alpha subunit ( K(i)=1.6 microM). MMP
      inhibitors such as the pyrimidine-2,4,6-trione derivative Ro 28-2653 that are
      more specific for gelatinases do not bind to hmeprin, presumably due to the
      subtle differences in the mode of zinc binding and active-site structure between
      the astacins and the MMPs.

PMID- 14594450
TI  - p38 MAP kinase signalling is required for hypertrophic chondrocyte
      differentiation.
AB  - Longitudinal growth of endochondral bones is accomplished through the co
      ordinated proliferation and hypertrophic differentiation of growth plate
      chondrocytes. The molecular mechanisms and signalling cascades controlling these
      processes are not well understood. To analyse the expression and roles of p38
      mitogen-activated protein kinases in this process, we have established a
      micromass system for the reproducible hypertrophic differentiation of mouse
      mesenchymal limb bud cells. Our results show that all four mammalian p38 kinase
      genes are expressed during the chondrogenic programme, as well as their upstream
      regulators MKK3 (mitogen-activated protein kinase kinase 3) and MKK6. Treatment
      of micromass cultures with pharmacological inhibitors of p38 results in a marked
      delay in hypertrophic differentiation in micromass cultures, indicating a
      requirement for p38 signalling in chondrocyte differentiation. Inhibition of p38
      kinase activity leads to reduced and delayed induction of alkaline phosphatase
      activity and matrix mineralization. In addition, p38 inhibition causes reduced
      expression of hypertrophic marker genes such as collagen X, matrix
      metalloproteinase 13 and bone sialoprotein. The function of p38 in hypertrophic
      differentiation appears to be mediated, at least in part, by the transcription
      factor myocyte enhancer factor 2C. In summary, we have demonstrated a novel
      requirement for p38 signalling in hypertrophic differentiation of chondrocytes
      and identified myocyte enhancer factor 2C as an important regulator of
      chondrocyte gene expression.

PMID- 14594451
TI  - Calcium mobilization and Rac1 activation are required for VCAM-1 (vascular cell
      adhesion molecule-1) stimulation of NADPH oxidase activity.
AB  - VCAM-1 (vascular cell adhesion molecule-1) plays an important role in the
      regulation of inflammation in atherosclerosis, asthma, inflammatory bowel disease
      and transplantation. VCAM-1 activates endothelial cell NADPH oxidase, and this
      oxidase activity is required for VCAM-1-dependent lymphocyte migration. We
      reported previously that a mouse microvascular endothelial cell line promotes
      lymphocyte migration that is dependent on VCAM-1, but not on other known adhesion
      molecules. Here we have investigated the signalling mechanisms underlying VCAM-1
      function. Lymphocyte binding to VCAM-1 on the endothelial cell surface activated
      an endothelial cell calcium flux that could be inhibited with anti-alpha4
      integrin and mimicked by anti-VCAM-1-coated beads. VCAM-1 stimulation of calcium
      responses could be blocked by an inhibitor of intracellular calcium mobilization,
      a calcium channel inhibitor or a calcium chelator, resulting in the inhibition of
      NADPH oxidase activity. Addition of ionomycin overcame the calcium channel
      blocker suppression of VCAM-1-stimulated NADPH oxidase activity, but could not
      reverse the inhibitory effect imposed by intracellular calcium blockage,
      indicating that both intracellular and extracellular calcium mobilization are
      required for VCAM-1-mediated activation of NADPH oxidase. Furthermore, VCAM-1
      specifically activated the Rho-family GTPase Rac1, and VCAM-1 activation of NADPH
      oxidase was blocked by a dominant negative Rac1. Thus VCAM-1 stimulates the
      mobilization of intracellular and extracellular calcium and Rac1 activity that
      are required for the activation of NADPH oxidase.

PMID- 14594454
TI  - Role of gonadotropin-releasing hormone (GnRH) in ovarian cancer.
AB  - The expression of GnRH (GnRH-I, LHRH) and its receptor as a part of an autocrine
      regulatory system of cell proliferation has been demonstrated in a number of
      human malignant tumors, including cancers of the ovary. The proliferation of
      human ovarian cancer cell lines is time- and dose-dependently reduced by GnRH and
      its superagonistic analogs. The classical GnRH receptor signal-transduction
      mechanisms, known to operate in the pituitary, are not involved in the mediation
      of antiproliferative effects of GnRH analogs in these cancer cells. The GnRH
      receptor rather interacts with the mitogenic signal transduction of growth-factor
      receptors and related oncogene products associated with tyrosine kinase activity
      via activation of a phosphotyrosine phosphatase resulting in downregulation of
      cancer cell proliferation. In addition GnRH activates nucleus factor kappaB
      (NFkappaB) and protects the cancer cells from apoptosis. Furthermore GnRH induces
      activation of the c-Jun N-terminal kinase/activator protein-1 (JNK/AP-1) pathway
      independent of the known AP-1 activators, protein kinase (PKC) or mitogen
      activated protein kinase (MAPK/ERK). Recently it was shown that human ovarian
      cancer cells express a putative second GnRH receptor specific for GnRH type II
      (GnRH-II). The proliferation of these cells is dose- and time-dependently reduced
      by GnRH-II in a greater extent than by GnRH-I (GnRH, LHRH) superagonists. In
      previous studies we have demonstrated that in ovarian cancer cell lines except
      for the EFO-27 cell line GnRH-I antagonist Cetrorelix has comparable
      antiproliferative effects as GnRH-I agonists indicating that the dichotomy of
      GnRH-I agonists and antagonists might not apply to the GnRH-I system in cancer
      cells. After GnRH-I receptor knock down the antiproliferative effects of GnRH-I
      agonist Triptorelin were abrogated while the effects of GnRH-I antagonist
      Cetrorelix and GnRH-II were still existing. In addition, in the ovarian cancer
      cell line EFO-27 GnRH-I receptor but not putative GnRH-II receptor expression was
      found. These data suggest that in ovarian cancer cells the antiproliferative
      effects of GnRH-I antagonist Cetrorelix and GnRH-II are not mediated through the
      GnRH-I receptor.

PMID- 14594456
TI  - Validity of a novel computerized cognitive battery for mild cognitive impairment.
AB  - BACKGROUND: The NeuroTrax Mindstreams computerized cognitive assessment system
      was designed for widespread clinical and research use in detecting mild cognitive
      impairment (MCI). However, the capability of Mindstreams tests to discriminate
      elderly with MCI from those who are cognitively healthy has yet to be evaluated.
      Moreover, the comparability between these tests and traditional
      neuropsychological tests in detecting MCI has not been examined. METHODS: A 2
      center study was designed to assess discriminant validity of tests in the
      Mindstreams Mild Impairment Battery. Participants were 30 individuals diagnosed
      with MCI, 29 with mild Alzheimer's disease (AD), and 39 healthy elderly. Testing
      was with the Mindstreams battery and traditional neuropsychological tests.
      Receiver operating characteristic (ROC) analysis was used to examine the ability
      of Mindstreams and traditional measures to discriminate those with MCI from
      cognitively healthy elderly. Between-group comparisons were made (Mann-Whitney U
      test) between MCI and healthy elderly and between MCI and mild AD groups.
      RESULTS: Mindstreams outcome parameters across multiple cognitive domains
      significantly discriminated among MCI and healthy elderly with considerable
      effect sizes (p < 0.05). Measures of memory, executive function, visual spatial
      skills, and verbal fluency discriminated best, and discriminability was at least
      comparable to that of traditional neuropsychological tests in these domains.
      CONCLUSIONS: Mindstreams tests are effective in detecting MCI, providing a
      comprehensive profile of cognitive function. Further, the enhanced precision and
      ease of use of these computerized tests make the NeuroTrax system a valuable
      clinical tool in the identification of elderly at high risk for dementia.

PMID- 14594453
TI  - SF-1 a key player in the development and differentiation of steroidogenic
      tissues.
AB  - Since its discovery in the early 1990s, the orphan nuclear receptor SF-1 has been
      attributed a central role in the development and differentiation of steroidogenic
      tissues. SF-1 controls the expression of all the steroidogenic enzymes and
      cholesterol transporters required for steroidogenesis as well as the expression
      of steroidogenesis-stimulating hormones and their cognate receptors. SF-1 is also
      an essential regulator of genes involved in the sex determination cascade. The
      study of SF-1 null mice and of human mutants has been of great value to
      demonstrate the essential role of this factor in vivo, although the complete
      adrenal and gonadal agenesis in knock-out animals has impeded studies of its
      function as a transcriptional regulator. In particular, the role of SF-1 in the
      hormonal responsiveness of steroidogenic genes promoters is still a subject of
      debate. This extensive review takes into account recent data obtained from SF-1
      haploinsufficient mice, pituitary-specific knock-outs and from transgenic mice
      experiments carried out with SF-1 target gene promoters. It also summarizes the
      pros and cons regarding the presumed role of SF-1 in cAMP signalling.

PMID- 14594455
TI  - A randomised controlled trial investigating the effect of nutritional
      supplementation on visual function in normal, and age-related macular disease
      affected eyes: design and methodology [ISRCTN78467674].
AB  - BACKGROUND: Age-related macular disease is the leading cause of blind
      registration in the developed world. One aetiological hypothesis involves
      oxidation, and the intrinsic vulnerability of the retina to damage via this
      process. This has prompted interest in the role of antioxidants, particularly the
      carotenoids lutein and zeaxanthin, in the prevention and treatment of this eye
      disease. METHODS: The aim of this randomised controlled trial is to determine the
      effect of a nutritional supplement containing lutein, vitamins A, C and E, zinc,
      and copper on measures of visual function in people with and without age-related
      macular disease. Outcome measures are distance and near visual acuity, contrast
      sensitivity, colour vision, macular visual field, glare recovery, and fundus
      photography. Randomisation is achieved via a random number generator, and masking
      achieved by third party coding of the active and placebo containers. Data
      collection will take place at nine and 18 months, and statistical analysis will
      employ Student's t test. DISCUSSION: A paucity of treatment modalities for age
      related macular disease has prompted research into the development of prevention
      strategies. A positive effect on normals may be indicative of a role of
      nutritional supplementation in preventing or delaying onset of the condition. An
      observed benefit in the age-related macular disease group may indicate a
      potential role of supplementation in prevention of progression, or even a degree
      reversal of the visual effects caused by this condition.

PMID- 14594457
TI  - Recruitment of heterosexual couples in public health research: a study protocol.
AB  - BACKGROUND: Public health research involving social or kin groups (such as sexual
      partners or family members), rather than samples of unrelated individuals, has
      become more widespread in response to social ecological approaches to disease
      treatment and prevention. This approach requires the development of innovative
      sampling, recruitment and screening methodologies tailored to the study of
      related individuals. METHODS: In this paper, we describe a set of sampling,
      recruitment and screening protocols developed to enlist urban, drug-using,
      heterosexual couples into a public health research study. This population is
      especially hard to reach because they are engaged in illegal and/or stigmatized
      behaviors. The protocols were designed to integrate adaptive sampling, street-
      and referral-based recruitment, and screening procedures to verify study
      eligibility and relationship status. DISCUSSION: Recruitment of heterosexual
      couples through one partner, preferably the female, can be an effective
      enlistment technique. Verification of relationship status is an important
      component of dyadic research. Comparison of parallel questionnaires administered
      to each member of a dyad can aid in the assessment of relationship status.
      However, multiple independent sources of information should be used to verify
      relationship status when available. Adaptive sampling techniques were effective
      in reaching drug-using heterosexual couples in an urban setting, and the
      application of these methods to other groups of related individuals in clinical
      and public health research may prove to be useful. However, care must be taken to
      consider potential sources of sampling bias when interpreting and generalizing
      study results.

PMID- 14594458
TI  - PCAS--a precomputed proteome annotation database resource.
AB  - BACKGROUND: Many model proteomes or "complete" sets of proteins of given
      organisms are now publicly available. Much effort has been invested in
      computational annotation of those "draft" proteomes. Motif or domain based
      algorithms play a pivotal role in functional classification of proteins.
      Employing most available computational algorithms, mainly motif or domain
      recognition algorithms, we set up to develop an online proteome annotation system
      with integrated proteome annotation data to complement existing resources.
      RESULTS: We report here the development of PCAS (ProteinCentric Annotation
      System) as an online resource of pre-computed proteome annotation data. We
      applied most available motif or domain databases and their analysis methods,
      including hmmpfam search of HMMs in Pfam, SMART and TIGRFAM, RPS-PSIBLAST search
      of PSSMs in CDD, pfscan of PROSITE patterns and profiles, as well as PSI-BLAST
      search of SUPERFAMILY PSSMs. In addition, signal peptide and TM are predicted
      using SignalP and TMHMM respectively. We mapped SUPERFAMILY and COGs to InterPro,
      so the motif or domain databases are integrated through InterPro. PCAS displays
      table summaries of pre-computed data and a graphical presentation of motifs or
      domains relative to the protein. As of now, PCAS contains human IPI, mouse IPI,
      and rat IPI, A. thaliana, C. elegans, D. melanogaster, S. cerevisiae, and S.
      pombe proteome.PCAS is available at http://pak.cbi.pku.edu.cn/proteome/gca.php
      CONCLUSION: PCAS gives better annotation coverage for model proteomes by
      employing a wider collection of available algorithms. Besides presenting the most
      confident annotation data, PCAS also allows customized query so users can inspect
      statistically less significant boundary information as well. Therefore, besides
      providing general annotation information, PCAS could be used as a discovery
      platform. We plan to update PCAS twice a year. We will upgrade PCAS when new
      proteome annotation algorithms identified.

PMID- 14594459
TI  - GeneViTo: visualizing gene-product functional and structural features in genomic
      datasets.
AB  - BACKGROUND: The availability of increasing amounts of sequence data from
      completely sequenced genomes boosts the development of new computational methods
      for automated genome annotation and comparative genomics. Therefore, there is a
      need for tools that facilitate the visualization of raw data and results produced
      by bioinformatics analysis, providing new means for interactive genome
      exploration. Visual inspection can be used as a basis to assess the quality of
      various analysis algorithms and to aid in-depth genomic studies. RESULTS:
      GeneViTo is a JAVA-based computer application that serves as a workbench for
      genome-wide analysis through visual interaction. The application deals with
      various experimental information concerning both DNA and protein sequences
      (derived from public sequence databases or proprietary data sources) and meta
      data obtained by various prediction algorithms, classification schemes or user
      defined features. Interaction with a Graphical User Interface (GUI) allows easy
      extraction of genomic and proteomic data referring to the sequence itself,
      sequence features, or general structural and functional features. Emphasis is
      laid on the potential comparison between annotation and prediction data in order
      to offer a supplement to the provided information, especially in cases of "poor"
      annotation, or an evaluation of available predictions. Moreover, desired
      information can be output in high quality JPEG image files for further
      elaboration and scientific use. A compilation of properly formatted GeneViTo
      input data for demonstration is available to interested readers for two
      completely sequenced prokaryotes, Chlamydia trachomatis and Methanococcus
      jannaschii. CONCLUSIONS: GeneViTo offers an inspectional view of genomic
      functional elements, concerning data stemming both from database annotation and
      analysis tools for an overall analysis of existing genomes. The application is
      compatible with Linux or Windows ME-2000-XP operating systems, provided that the
      appropriate Java Runtime Environment is already installed in the system.

PMID- 14594460
TI  - Are there answers?

PMID- 14594461
TI  - Crossing species boundaries.
AB  - This paper critically examines the biology of species identity and the morality
      of crossing species boundaries in the context of emerging research that involves
      combining human and nonhuman animals at the genetic or cellular level. We begin
      with the notion of species identity, particularly focusing on the ostensible
      fixity of species boundaries, and we explore the general biological and
      philosophical problem of defining species. Against this backdrop, we survey and
      criticize earlier attempts to forbid crossing species boundaries in the creation
      of novel beings. We do not attempt to establish the immorality of crossing
      species boundaries, but we conclude with some thoughts about such crossings,
      alluding to the notion of moral confusion regarding social and ethical
      obligations to novel interspecies beings.

PMID- 14594462
TI  - Creating human-nonhuman chimeras: of mice and men.

PMID- 14594463
TI  - Chimeras and "human dignity".

PMID- 14594464
TI  - The wisdom of Leon the professional [ethicist].

PMID- 14594465
TI  - Crossing perspectival chasms about species.

PMID- 14594466
TI  - Moral ambiguity? Yes. Moral confusion? No.

PMID- 14594467
TI  - Species and races, chimeras, and multiracial people.

PMID- 14594468
TI  - Crossing species boundaries is even more controversial than you think.

PMID- 14594469
TI  - A scientist crossing a boundary: a step into the bioethical issues surrounding
      stem cell research.

PMID- 14594470
TI  - Ethics and species integrity.

PMID- 14594472
TI  - Defining chimeras...and chimeric concerns.

PMID- 14594471
TI  - In defense of stem cell chimeras: a response to "Crossing species boundaries".

PMID- 14594473
TI  - Crossing species boundaries and making human-nonhuman hybrids: moral and legal
      ramifications.

PMID- 14594474
TI  - The humane imperative: a moral opportunity.

PMID- 14594475
TI  - Human-animal transgenesis and chimeras might be an expression of our humanity.

PMID- 14594476
TI  - The bioethics of fiction: the chimera in film and print.

PMID- 14594477
TI  - Drawing the line at not-fully-human: what we already know.

PMID- 14594478
TI  - What's wrong with confusion?

PMID- 14594479
TI  - A legal perspective on humanity, personhood, and species boundaries.

PMID- 14594480
TI  - Industry-to-physician marketing and the cost of prescription drugs.

PMID- 14594481
TI  - Hopes against hopeful monsters.

PMID- 14594482
TI  - Large or small, a gift is a gift is a gift.

PMID- 14594483
TI  - Transgenic chimeras.

PMID- 14594484
TI  - The death of common sense.

PMID- 14594485
TI  - No real categories, only chimeras and illusions: the interplay between morality
      and science in debates over embryonic chimeras.

PMID- 14594486
TI  - The moral insignificance of crossing species boundaries.

PMID- 14594487
TI  - Patents on human-animal chimeras and threats to human dignity.

PMID- 14594488
TI  - In defense of the moral relevance of species boundaries.

PMID- 14594489
TI  - All gifts large and small: toward an understanding of the ethics of
      pharmaceutical industry gift-giving.
AB  - Much attention has been focused in recent years on the ethical acceptability of
      physicians receiving gifts from drug companies. Professional guidelines recognize
      industry gifts as a conflict of interest and establish thresholds prohibiting the
      exchange of large gifts while expressly allowing for the exchange of small gifts
      such as pens, note pads, and coffee. Considerable evidence from the social
      sciences suggests that gifts of negligible value can influence the behavior of
      the recipient in ways the recipient does not always realize. Policies and
      guidelines that rely on arbitrary value limits for gift-giving or receipt should
      be reevaluated.

PMID- 14594490
TI  - Bribes for doctors: a gift for bioethicists?

PMID- 14594491
TI  - Voluntary self-regulatory codes: what should we expect?

PMID- 14594492
TI  - Small gifts, conflicts of interest, and the zero-tolerance threshold in medicine.

PMID- 14594493
TI  - Cheap trinkets, effective marketing: small gifts from drug companies to
      physicians.

PMID- 14594494
TI  - The ethics of pharmaceutical industry gift-giving: the role of a professional
      association.

PMID- 14594495
TI  - Pharmaceutical industry influences on physician prescribing: gifts, quasi-gifts,
      and patient-directed gifts.

PMID- 14594496
TI  - All rationalizations large and small.

PMID- 14594497
TI  - Pens and other pharmaceutical industry gifts.

PMID- 14594498
TI  - Access to medication and drug company sales practices: setting priorities for
      critique and advocacy.

PMID- 14594499
TI  - Lunch with Lilly: who pays?

PMID- 14594500
TI  - Banning pens and pads misses the main point.

PMID- 14594501
TI  - The invisible influence of industry inducements.

PMID- 14594502
TI  - The therapeutic promise of nonembryonic stem cells--where's the beef?

PMID- 14594503
TI  - Immunostimulatory oligonucleotides: ready for immunotherapy prime time!

PMID- 14594504
TI  - CD34+ cells and CD34+CD38- subset from mobilized blood show different patterns of
      adhesion molecules compared to those from steady-state blood, bone marrow, and
      cord blood.
AB  - As suggested previously, a down-regulation of some cellular adhesion molecules
      (CAMs) on CD34(+) hematopoietic progenitor cells (HPC) may contribute to their
      egress from bone marrow (BM) to peripheral blood (PB) by decreasing their
      adhesion to BM stromal cells. Besides counting the percentage of CAM-positive
      cells, we decided to define clearly the antigen density (AgD) of the CAM on
      mobilized- and steady-state CD34(+) HPC using QIFIKIT calibration beads. Five
      sources of cells were compared: PB and BM from normal donors (nPB, nBM) cord
      blood (CB), mobilized PB obtained from leukapheresis products (LKP), and
      mobilized BM (mBM) samples. In our study the CAM-AgD was the lowest on CD34(+)
      cells in LKP which, on the contrary, contained the highest percentage of
      CD117(+), CD54(+), CD58(+) cell subsets. As for CB, a greater proportion of
      CD44(+) and CD62L(+) cells was observed in LKP than in other products. The LKP
      CD34(+) cell population contained a greater percentage of CD11a(+) cells when
      compared to mBM, but the lowest percentage of CD49d(+) and CD49e(+) cells when
      compared to all products. The proportion of the CD34(+)CD38(-) immature subset
      expressing CD11a, CD44, CD54, or CD62L was greater in LKP than in mBM; the CD62L
      AgD was higher in LKP than in mBM. This quantitative analysis clearly showed a
      downregulation of all CAM on LKP-CD34(+). The CD44, CD62L, CD11a, and CD54 AgD
      decrease appears to be specifically involved in the egress of the CD34(+) subsets
      into PB. The control of antigen density of these adhesion molecules is likely to
      be clinically important for effective mobilization of HPC as well as for rapid
      engraftment following HPC transplant.

PMID- 14594506
TI  - Reactivation of fetal hemoglobin in adult stem cell erythropoiesis by
      transforming growth factor-beta.
AB  - Treatment of adult blood-derived stem cells with transforming growth factor (TGF
      beta) during the first 3-4 days in culture increases the proportions and absolute
      numbers of erythroid cells subsequently expressing fetal hemoglobin (F+ cells).
      The change in F+ cell proportions may be due to globin switching or to selective
      effects on the expansion of stem cell subpopulations with different globin
      expression programs. To distinguish between the two mechanisms, we compared the
      effects of TGF-beta on proliferation and globin expression with the effects of
      well-researched agents known to increase fetal hemoglobin (HbF) in sickle cell
      patients. Hydroxyurea suppressed F+ and F- erythroid cells equally and thus did
      not affect the F+ proportions. Aza-cytidine and sodium butyrate, known
      reactivators of gamma-globin expression, suppressed F+ and F- cells
      differentially and increased F+ cell proportions with a dependence on treatment
      timing similar to that of TGF-beta. In contrast to TGF-beta, these agents had no
      superimposed stimulatory effect. The data suggest that TGF-beta reactivates gamma
      globin expression, combined with a sequential stimulation and suppression of
      erythropoiesis. The similarities between the actions of TGF-beta and therapeutic
      reactivators of fetal hemoglobin make it conceivable that TGF-beta may have the
      potential to increase HbF in patients with beta-hemoglobin disorders.

PMID- 14594505
TI  - Colony-stimulating activity of fetal liver cells: synergistic role of stem cell
      factor in bone marrow recovery from aplastic anemia.
AB  - Previously, we and others have shown that fetal liver infusion (FLI) leads to
      autologous hematopoietic improvement in 40-54% of patients with aplastic anemia.
      However, whether this recovery was spontaneous or the effect of the infused liver
      cells was not clear. To dissect the role of FLI in autologous hematopoietic
      recovery, the colony-supporting potential of fetal liver-conditioned medium
      (FLCM) was evaluated in bone marrow (BM) cells of normal adult and aplastic
      anemia patients. In both cases, each sample of FLCM supported the growth of
      colony-forming cells in semi solid culture medium. The FLCM was assayed for the
      presence of four principal colony-stimulating cytokines, namely stem cell factor
      (SCF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3
      (IL-3), and erythropoietin (Epo). While GM-CSF, IL-3, and Epo were present in
      insignificant amounts or were altogether absent, 50-635 pg/ml of SCF was found in
      8 of the 13 FLCM samples tested. Preliminary results of bioneutralization assay
      indicated the possible role of SCF, secreted by the FL cells, in colony
      supporting activity of aplastic anemia and normal BM cells. Overall, our in vitro
      study implicates the paracrine role of infused FL cells in regenerating
      autologous hematopoiesis in aplastic anemia patients.

PMID- 14594507
TI  - Ex vivo immunotherapy for patients with benzene-induced aplastic anemia.
AB  - Aplastic anemia is a bone marrow failure disorder characterized by pancytopenia
      and a hypocellular marrow. Benzene is one of the etiologic agents capable of
      inducing the disease. With modest to severe aplastic anemia, one previously
      untreated patient and 13 patients who had failed immunosuppressive therapy were
      studied. Peripheral blood mononuclear cells from patients were expanded in vitro
      with a combination of cytokines and a calcium-mobilizing agents for 2 days, and
      the activated cells were infused intravenously once a week. In some cases, we
      used allogenic leukocytes instead of autologous cultured lymphocytes. After 6-35
      weeks of the treatment, all patients had multilineage responses to this therapy
      and achieved complete disease remission, defined as normal blood count,
      independence from transfusion, and normal bone marrow histology. The therapy was
      safe and well tolerated with minimal side effects. The cultured cells produced
      interleukin-1 and induced immune responses in vivo. Serum interleukin-2 and
      interferon- gamma were detected following cell infusion. Finally, patients had
      sustained responses to the therapy and no relapse was found up to 18 months after
      cellular therapy.

PMID- 14594508
TI  - Large-scale immunomagnetic selection of CD14+ monocytes to generate dendritic
      cells for cancer immunotherapy: a phase I study.
AB  - Dendritic cells (DC) are professional antigen-presenting cells that are widely
      used in the experimental immunotherapy of cancer. For clinical use GMP-like
      protocols for the preparation of functionally active dendritic cells (DC) in
      large numbers and at high purity are needed. However, the currently available
      protocols have certain disadvantages. In this study we tested the generation and
      clinical applicability of DC from monocyte preparations produced by
      immunomagnetic CD14(+) selection using a semiautomated clinical scale
      immunomagnetic column. Peripheral blood mononuclear cells (PBMC) of 10 patients
      with metastatic solid tumors were used. With the immunomagnetic separation, we
      obtained a cell suspension of high CD14(+) purity (median 97.4%, range 94.9-99.0)
      with a high monocyte yield (median 82.3%, range 63.9-100.0). Differentiation of
      CD14(+) cells into mature monocyte-derived DC was induced by incubation with IL
      4, GM-CSF, TNF-alpha, PGE(2), IL-1 beta, and IL-6. Mature DC showed a high
      expression of CD83, HLA-DR, and the co-stimulatory molecules CD80 and CD86.
      Overall CD83(+) yield was 12.1% (range 4.0-29.4). Allogeneic T stimulatory
      capacity could be demonstrated for all DC preparations in proliferation assays.
      No significant differences in marker expression or T cell stimulation was
      detected between fresh DC and those derived from cryopreserved immature DC.
      Clinical administration of autologous DC by three different parenteral routes was
      tolerated by all 10 patients without systemic signs of toxicity. Our results
      indicate that immunomagnetic isolation of CD14(+) monocytes using the CliniMACS
      device is a suitable method for clinical-scale generation of functional DC under
      GMP-grade conditions. The selection can be performed in a closed system.
      Therefore, immunomagnetic CD14(+) selection can be seen as an alternative way to
      generate DC for clinical tumor vaccination protocols.

PMID- 14594509
TI  - Functional evaluation of proliferative T cell responses in patients with severe T
      lymphopenia: characterization of optimal culture conditions and standardized
      activation signals for a simple whole blood assay.
AB  - In this methodological study, we describe an assay for analysis of proliferative
      T cell responses in patients with severe leukopenia. Severe treatment-induced
      cytopenia is observed in patients with malignant disorders who receive
      conventional intensive chemotherapy or autologous stem cell transplantation. The
      quantitative T cell defect can then be characterized by flow cytometric analysis
      of membrane molecule expression, whereas the functional status of the remaining T
      cell population is more difficult to evaluate. In the present study, we describe
      a standardized whole blood assay that requires small sample volumes and can be
      used for repeated analysis even in severely ill patients. The assay is based on
      the following strategy: (i) blood samples are diluted with the serum-free medium
      X-vivo 10, (ii) T cells are activated either with monoclonal immunoglobulin E
      (IgE) anti-CD3 or anti-CD3 plus anti-CD28; (iii) T cell proliferation is assayed
      by [(3)H]thymidine incorporation after 4 days of in vitro culture. These
      proliferative responses are not affected by the plasma levels of interleukin-2
      (IL-2), sIL-2-R alpha, IL-7 and IL-15, and the kinetics of the response are not
      altered by the presence of exogenous cytokines. Detectable proliferation is
      observed for most patients with treatment-induced cytopenia. We conclude that the
      assay can be used for functional characterization of remaining T lymphocytes in
      patients with severe T lymphopenia.

PMID- 14594510
TI  - Low efficiency of a newly introduced high-density microparticles method for B
      cell depletion in multiple myeloma patients undergoing autologous hematopoietic
      stem cell transplantation.
AB  - Autologous peripheral blood stem cell (PBSC) transplantation proved to increase
      complete remission (CR) and DFS in multiple myeloma (MM) patients. CD34(+) cell
      selection has been used to reduce possible myeloma cell contamination in the
      graft, but it has not been showed to offer substantial advantages when compared
      to unpurged grafts; on the contrary, an increase of infectious complications was
      observed. We investigated the feasibility of a new negative-selection method in
      this setting. B cell negative selection was performed by using Eligix B cell HDM
      method. B cell contamination in the yield and in the final product was
      investigated by flow cytometry. Three patients with newly diagnosed MM entered
      the study. CD34(+) cell recovery in the three procedures was 73, 97, and 106%,
      and CD3(+) cell recovery was 88, 86, and 102%, respectively. CD20(+) cell
      depletion was 100% in all procedures, while CD19(+) cell depletion was 0.37,
      1.21, and 0.07 log, respectively. We found an unexpected unreliability and a low
      efficiency in this B cell depletion method and suggest the need for further
      extensive testing before its introduction in the preclinical and clinical
      settings, at least in MM patients. In fact, reasons of such unsatisfactory
      results are still controversial: platelet contamination/activation in the
      preselection product, plasma protein interference, reduced CD19 antigen
      expression on immature B cells, lack of specificity of anti-CD19 monoclonal
      antibodies, instable binding between anti-CD19-coated high-density microparticles
      (HDM) and CD19 antigen may, alone or in combination, be involved in the system's
      low performance.

PMID- 14594512
TI  - Supplementation of conventional freezing medium with a combination of catalase
      and trehalose results in better protection of surface molecules and functionality
      of hematopoietic cells.
AB  - Our previous studies had shown that a combination of the bio-antioxidant catalase
      and the membrane stabilizer trehalose in the conventional freezing mixture
      affords better cryoprotection to hematopoietic cells as judged by clonogenic
      assays. In the present investigation, we extended these studies using several
      parameters like responsiveness to growth factors, expression of growth factor
      receptors, adhesion assays, adhesion molecule expression, and long-term culture
      forming ability. Cells were frozen with (test cells) or without additives
      (control cells) in the conventional medium containing 10% dimethylsulfoxide
      (DMSO). Experiments were done on mononuclear cells (MNC) from cord blood/fetal
      liver hematopoietic cells (CB/FL) and CD34(+) cells isolated from frozen MNC. Our
      results showed that the responsiveness of test cells to the two early-acting
      cytokines, viz. interleukin-3 (IL-3) and stem cell factor (SCF) in CFU assays was
      better than control cells as seen by higher colony formation at limiting
      concentrations of these cytokines. We, therefore, analyzed the expression of
      these two growth factor receptors by flow cytometry. We found that in
      cryopreserved test MNC, as well as CD34(+) cells isolated from them, the
      expression of both cytokine receptors was two- to three-fold higher than control
      MNC and CD34(+) cells isolated from them. Adhesion assays carried out with CB/FL
      derived CD34(+) cells and KG1a cells showed significantly higher adherence of
      test cells to M210B4 than respective control cells. Cryopreserved test MNC as
      well as CD34(+) cells isolated from them showed increased expression of adhesion
      molecules like CD43, CD44, CD49d, and CD49e. On isolated CD34(+) cells and KG1a
      cells, there was a two- to three-fold increase in a double-positive population
      expressing CD34/L-selectin in test cells as compared to control cells. Long-term
      cultures (LTC) were set up with frozen MNC as well as with CD34(+) cells.
      Clonogenic cells from LTC were enumerated at the end of the fifth week. There was
      a significantly increased formation of CFU from test cells than from control
      cells, indicating better preservation of early progenitors in test cells. Our
      results suggest that use of a combination of catalase and trehalose as a
      supplement in the conventional freezing medium results in better protection of
      growth factor receptors, adhesion molecules, and functionality of hematopoietic
      cells, yielding a better graft quality.

PMID- 14594511
TI  - Standardization of the CFU-GM assay: Advantages of plating a fixed number of
      CD34+ cells in collagen gels.
AB  - We investigated whether plating a stable amount of CD34(+) cells improves the CFU
      GM assay. Data of CFU-GM assays performed with leukaphereses products in two
      transplant centers using a commercial collagen-based medium and unified CFU-GM
      scoring criteria were pooled and analyzed according to the numbers of CD34(+)
      cells plated. A first series of 113 CFU-GM assays was performed with a fixed
      number of mononuclear cells (i.e., a variable number of CD34(+) cells). In these
      cultures the CFU-GM/CD34 ratio varied according to the number of CD34(+) cells
      plated: median CFUGM/CD34 ratios were 1/6.2 to 1/6.6 for grafts containing <2%
      CD34(+) cells, vs. 1/10.2 for grafts containing > or =2% CD34(+) cells. The
      median CFU-GM/CD34 ratio also varied depending on pathology: 1/9.3 for multiple
      myeloma (MM), 1/6.8 for Hodgkin's disease (HD), 1/6.5 for non-Hodgkin lymphoma
      (NHL), and 1/4.5 for solid tumors (ST). A second series of 95 CFU-GM assays was
      performed with a fixed number of CD34(+) cells (220/ml). The range of median CFU
      GM/CD34 ratios was narrowed to 1/7.0 to 1/5.2, and coefficients of variation for
      CFU-GM counts decreased by half to 38.1% (NHL), 36.1% (MM), 49.9% (HD), and 22.4%
      (ST). In addition, CFU-GM scoring was facilitated as the percentages of cultures
      with >50 CFU/GM/ml decreased from 6.7% to 43.8% when a variable number of CD34(+)
      cells was plated, to 4.5% to 16.7% when 220 CD34(+) cells/ml were plated. Hence,
      plating a fixed number of CD34(+) cells in collagen gels improves the CFU-GM
      assay by eliminating cell number-related variability and reducing pathology
      related variability in colony growth.

PMID- 14594513
TI  - T cell generation including positive and negative selection ex vivo in a three
      dimensional matrix.
AB  - The prevailing paradigm is that T cell differentiation is dependent on
      interactions between stem cells and neuroectodermal thymic cells in the context
      of a three-dimensional environment. We evaluated the utility of a three
      dimensional matrix, the Cytomatrix, to facilitate T cell differentiation. Thymus
      stroma grown on the Cytomatrix and seeded with hematopoietic progenitors was
      observed to support the development of both CD4(+) and CD8(+) T cells. Murine
      transgenic models used to address T cell selection demonstrated that both
      positive and negative selection was maintained in the context of MHC Class I.
      These data demonstrate that this in vitro system using neuroectoderm tissue is
      capable of the efficient production of T cells from hematopoietic progenitors and
      presents the possibility of generating and adoptively transferring immune cells
      to patients.

PMID- 14594515
TI  - An efficient large-scale thawing procedure for cord blood cells destined for
      selection and ex vivo expansion of CD34+ cells.

PMID- 14594514
TI  - Dendritic cell culture: a simple closed culture system using ficoll, monocytes,
      and a table-top centrifuge.
AB  - Dendritic cells (DCs) are potent antigen-presenting cells involved in the
      induction of T cell-mediated immune responses and as such have emerged as
      important candidates for cellular-based therapies. Critical to safe clinical use
      is the easy manipulation of DCs and their precursors in a closed system. We have
      developed a serum-free, closed culture system applying a simple wash-Ficoll
      centrifugation method to reduce platelet and red blood cell (RBC) contamination.
      This procedure optimized adherence of monocytes (44 +/- 10.9% recovery, >85%
      expressed CD14(+)/CD163(+)) for the generation of DCs from mononuclear cell (MNC)
      apheresis units. Most RBCs and up to 98% of platelets were removed. Following
      density sedimentation, cell viability remained high (98 +/- 2%) with only minimal
      loss of monocytes (3 +/- 3%). Importantly, Ficoll-treated monocytes retained
      their ability to differentiate to mature DCs demonstrated by morphology,
      phenotype (MHC class II(+), CD1a(+), CD80(+), CD86(+), and CD83(+)), ability to
      stimulate mixed lymphocyte responses (MLR), present antigen, and produce
      interleukin-12 (IL-12). Nonadherent CD3(+) (80 +/- 4%) were also isolated for
      functional assays. Ficoll can be easily incorporated into a simple adherence
      based closed system for collection of lymphocytes and adherent monocytes for DC
      culture. The procedure is relatively fast (effective working time 5-6 h), does
      not impair monocyte function or induce substantial cell activation, and can be
      performed economically using equipment found in a typical blood banking
      environment.

PMID- 14594516
TI  - Comparison of TTS-fentanyl with sustained-release oral morphine in the treatment
      of patients not using opioids for mild-to-moderate pain.
AB  - OBJECTIVE: This randomised, multicentre, direct open comparative trial evaluated
      the efficacy, treatment convenience, tolerability and safety aspects of
      transdermal therapeutic system (TTS)-fentanyl and sustained-release oral morphine
      (SRM) in both opioid-naive patients with moderate-to-severe cancer-related pain
      and in patients who had already been using opioids for mild-to-moderate pain. The
      two treatment groups were run in parallel. Special attention was paid to
      constipation, nausea/vomiting, drowsiness and respiratory depression. PATIENTS
      AND METHODS: The 131 enrolled patients started the 4-week treatment at low doses
      of opioid (25 microg/h TTS-fentanyl for 3 days or 30 mg SRM every 12 h) and were
      individually titrated. Tolerability, efficacy and safety were assessed throughout
      the study period. Frequency of constipation was the primary study variable and
      accordingly the study was powered for this. Both patients and investigators made
      a global treatment evaluation. RESULTS: TTS-fentanyl and SRM were shown to be
      equally effective. Pain control and sleep quality improved with both treatments.
      None of the patients developed respiratory depression. Statistically
      significantly more patients in the SRM treatment group discontinued the trial
      prematurely (59% vs 27%; p < 0.001), particularly due to adverse events (36% vs
      4%; p < 0.001). Fewer patients in the TTS-fentanyl than in the SRM treatment
      group reported constipation during the trial. This finding was statistically
      significant after 1 week of treatment (27% vs 57%; p = 0.003). The favourable
      tolerability profile of TTS-fentanyl was also reflected in both the patient and
      the investigator global evaluation of the treatment. Patient assessment favoured
      TTS-fentanyl treatment in terms of a significantly lower rate of troublesome side
      effects ('quite a bit' to 'very much' troublesome side-effects in 14% vs 36% of
      patients; p = 0.003) and less interruption of daily activities (absence of any
      interruption of daily activities in 88% vs 63% of patients; p = 0.012).
      Investigators scored TTS-fentanyl as significantly better with respect to 'side
      effects' (p = 0.039) and 'overall impression' (p = 0.013). Sub-analyses of opioid
      naive users gave similar results. CONCLUSION: These data indicate that TTS
      fentanyl, when used as an opioid of first choice in the treatment of cancer
      related pain, is as effective as, but better tolerated than, SRM, including in
      opioid-naive patients.

PMID- 14594517
TI  - The evolving role of telomerase inhibitors in the treatment of cancer.
AB  - Telomerase is a ribonucleoprotein that maintains telomeres and is essential for
      cellular immortality and tumour growth. The differential expression of telomerase
      in cancer cells makes it an attractive therapeutic target. Anti-sense
      oligonucleotides directed against the RNA template of hTR and small molecules
      that can interact and stabilise the G-quadruplex represent promising therapeutic
      strategies. Human trials investigating the potential role of the catalytic
      subunit hTERT as a universal cancer vaccine have already commenced. Alternative
      lengthening of telomeres (ALT) and efficacy delay remain important limitations to
      anti-telomerase therapy.

PMID- 14594518
TI  - Switching treatment-resistant patients with schizophrenia or schizoaffective
      disorder to olanzapine: a one-year open-label study with five-year follow-up.
AB  - OBJECTIVE: To determine whether patients with treatment-resistant schizophrenia
      or schizoaffective disorder would respond when switched to olanzapine and whether
      they could maintain their response on this atypical antipsychotic. RESEARCH
      DESIGN AND METHODS: In this single-center, observational, 1-year open-label
      study, a cohort of patients was switched to olanzapine due to failure on previous
      treatment. The patients were followed up (retrospectively) for an additional 5
      years. Patients had schizophrenia or schizoaffective disorder and all but one
      were treatment-resistant. The starting dose was 10 mg/day, with dosage
      adjustments based on physician judgment. MAIN OUTCOME MEASURES: The CGI-S and CGI
      I scales were the primary outcome measures. During the observation period,
      positive and negative symptoms, hospital readmission rates and duration of
      hospitalization were measured, and treatment-emergent adverse events recorded.
      RESULTS: Mean age of patients (n = 25) was 39.7 years; 19 were male, and all were
      Caucasian. The mean number of antipsychotics used prior to olanzapine was 4.6
      with risperidone (76%) being the most common. The mean duration of olanzapine
      therapy was 8.6 months. The average number of hospital admissions per patient
      dropped from 1.32 during the year prior to olanzapine therapy to 0.39 after
      starting olanzapine. Total number of hospital days was 1042 the year before and
      258 the year after olanzapine treatment. The mean CGI-S score improved from
      markedly ill at baseline to borderline/mildly ill at study end. The mean CGI-I
      score was rated much improved at study end. Few adverse events occurred during
      the study. Twelve patients remained on olanzapine monotherapy after 5 years of
      treatment (mean duration of 62 months). CONCLUSIONS: Olanzapine may be a
      treatment option for patients who fail to respond to treatment with other
      antipsychotics. Importantly, this is one of the first reports showing that
      patients with schizophrenia can be maintained on atypical antipsychotic
      monotherapy for at least 5 years.

PMID- 14594519
TI  - The advantages of intravenous renal anaemia treatment in an undernourished
      patient with chronic kidney disease.
AB  - The subcutaneous (SC) treatment of renal anaemia in undernourished patients has
      potential limitations. In this case report we demonstrate the value of
      intravenous (IV) darbepoetin alfa in such a patient who experienced difficulty
      tolerating SC recombinant human erythropoietin (rHuEPO) therapy due to severe
      malnutrition. Intravenous treatment of renal anaemia in a malnourished patient is
      preferred because the absence of SC fat makes SC administration difficult. In
      such patients, darbepoetin alfa is the treatment of choice as it is administered
      less frequently than other erythropoietic therapies and is more effective at
      maintaining target haemoglobin (Hb) concentrations. In contrast to rHuEPO,
      darbepoetin alfa also has the additional advantage of bioequivalent IV and SC
      dose requirements.

PMID- 14594520
TI  - Pharmacological agents used for the treatment of stress urinary incontinence in
      women.
AB  - Stress urinary incontinence (SUI) is the involuntary loss of urine associated
      with physical activities such as running, jumping, or lifting, or with sneezing
      and coughing. For many patients it can be a very bothersome symptom, causing
      social isolation, loss of self-esteem, and increased expenses. Although there is
      currently no single medication approved worldwide for the treatment of SUI, a
      variety of off-label agents are often prescribed. This paper reviews the current
      pharmacological treatment options for SUI, describing the mechanism of action,
      efficacy, and possible adverse effects of each. A new centrally-acting compound
      with dual activity as a balanced serotonin and norepinephrine reuptake inhibitor,
      duloxetine, may offer a promising new approach for treatment.

PMID- 14594521
TI  - Pharmacodynamics of omalizumab: implications for optimised dosing strategies and
      clinical efficacy in the treatment of allergic asthma.
AB  - OBJECTIVE: Omalizumab (Xolair), is a recombinant humanised monoclonal anti
      immunoglobulin E (IgE) antibody, for the treatment of allergic asthma. This
      review describes how the correlation between clinical outcomes and a suitable
      surrogate marker (free serum IgE) led to the development of an individualised
      dosing strategy for omalizumab. It also demonstrates how subsequent studies using
      this dosing strategy were able to achieve low levels of IgE and clinical benefit.
      DATA SOURCES: Published articles and data on file (Novartis Pharma AG,
      Genentech). RESULTS: Studies in patients with IgE-mediated diseases of the
      airways have shown that clinical benefit with omalizumab is observed when free
      IgE levels in serum are reduced to 50 ng/ml (20.8 IU/ml) or less (target 25 ng/ml
      (10.4 IU/ml)). The ability of omalizumab to reduce free IgE levels to such levels
      is dependent on dose, the patient's weight and baseline IgE level. To simplify
      dosing, and ensure that free IgE reduction is achieved, an individualised tiered
      dosing table was developed from which patients with asthma, depending on weight
      and starting IgE level, receive omalizumab 150-375 mg by subcutaneous injection
      every 2 or 4 weeks. This dosing strategy has proved clinically efficacious for
      improving disease control in patients with allergic asthma, as shown by
      significantly lower exacerbation rates and decreased dependence on treatment with
      inhaled corticosteroids, along with improvements in symptoms, lung function and
      usage of rescue bronchodilators. CONCLUSIONS: The clinical efficacy of omalizumab
      has been optimised through the development of an individualised dosing table that
      emerged from an understanding of the pharmacodynamics of this agent.

PMID- 14594522
TI  - An open-label study of a second course of hylan G-F 20 for the treatment of pain
      associated with knee osteoarthritis.
AB  - OBJECTIVE: To evaluate the efficacy and tolerability of a second course of hylan
      G-F 20 for the treatment of osteoarthritic knee pain in patients who experienced
      a clinical benefit with an initial course of therapy. RESEARCH DESIGN AND
      METHODS: In this prospective, open-label study, men or women (>/=40 years of age)
      with knee osteoarthritis (OA) received three weekly injections of hylan G-F 20.
      Consecutive patients who requested a second course of hylan G-F 20 therapy due to
      OA knee pain subsequent to pain relief with a first course of therapy were
      enrolled between October 26, 2000 and January 18, 2001. MAIN OUTCOME MEASURES:
      Pain while walking on a flat surface (Western Ontario and McMaster's Universities
      Osteoarthritis Index, WOMAC, question A1), WOMAC domain C (physical functioning),
      full WOMAC, and patient and investigator overall visual analog scales (VAS).
      Efficacy variables were measured at baseline and at weeks 1, 2, 4, 8, 12 and 26.
      An analgesic washout was required before all efficacy evaluations. RESULTS:
      Patients receiving at least one injection of hylan G-F 20 (n = 71) were
      predominantly Caucasian (84.5%) and female (64.8%), with a mean age of 65.5 years
      and mean weight of 200.1 pounds. The mean time between the first and second
      courses of hylan G-F 20 was 19.6 months (median 17.6 months). With hylan G-F 20,
      pain while walking on a flat surface was significantly lower (p < 0.001) than
      baseline at all time points up to week 26 (mean +/- SEM: -1.40 +/- 0.10 at week
      26). Actual scores decreased from 2.4 +/- 0.10 at baseline to 0.97 +/- 0.11 at
      week 26. Scores for the WOMAC domain C, full WOMAC and patient and investigator
      overall VAS also significantly improved (p < 0.001) at all time points. A second
      course of hylan G-F 20 was generally well-tolerated, based on the low incidence
      of local adverse events (AEs) - only one patient (1.4%) experienced a severe
      event, the types of AEs, and the fact that no patients discontinued the study due
      to these AEs. The types of related AEs observed were not qualitatively different
      from those listed in the current product information and published literature.
      CONCLUSION: A second course of hylan G-F 20 therapy is an appropriate therapy for
      the treatment of OA knee pain in patients who had a previous favorable clinical
      response. For continued relief of osteoarthritis knee pain, this study supports
      repeat use of hylan G-F 20 in these patients.

PMID- 14594523
TI  - Clinical experience of galantamine in dementia: a series of case reports.
AB  - OBJECTIVE: To use case studies to add the benefit of personal experience with
      galantamine to published literature and to demonstrate the type of patients that
      may benefit from this treatment. METHODS: We describe eleven patients, aged 57-90
      years, fulfilling the consensus diagnostic criteria for probable Alzheimer's
      disease, mixed dementia, vascular dementia, Lewy body dementia or Parkinson's
      dementia. All patients were treated with galantamine that may enhance cholinergic
      function in the brain by inhibiting acetylcholinesterase and potentiating the
      effects of acetylcholine at nicotinic acetylcholine receptors. Clinical features
      were rated according to eight assessment scales in old age psychiatry and
      additional information was obtained from family and other carers. In some cases
      caregiver distress was measured. RESULTS: All patients described showed a general
      improvement in cognition and neuropsychiatric symptoms, although observed
      improvements and effects were not always reflected by the results of formal
      assessments. Several patients became more independent, particularly in their
      activities of daily living, and treatment was felt to have helped maintain
      independence in their home environment, either alone or with their family or
      carers. One man continued in employment. Adverse events included nausea and
      vomiting. CONCLUSIONS: Outcomes in this case series indicate that galantamine is
      well tolerated and highlight aspects of the different side-effect profiles of the
      anticholinesterase inhibitors. Subjective benefits were not always apparent from
      objective measures. These case studies demonstrate the type of patients that may
      benefit from galantamine.

PMID- 14594524
TI  - Simulation of the effect of patient nonadherence on plasma concentrations of
      carbamazepine from twice-daily extended-release capsules.
AB  - OBJECTIVE: Carbamazepine (CBZ) effectively treats simple, complex, and
      secondarily generalized partial seizures. Computer simulations were carried out
      to investigate the effect of missing or delaying doses of carbamazepine extended
      release capsules (CBZ-ERC) on plasma CBZ levels and the optimal dosing strategy
      to return plasma concentrations to therapeutic levels. PATIENTS AND METHODS: A
      one-compartment open model with first-order absorption and elimination was
      generated from the results of a previous study measuring plasma concentrations
      following one 400-mg fasting dose of CBZ-ERC. The model was used to simulate
      plasma CBZ concentrations following multiple doses given every 12 h to
      hypothetical long-term CBZ-treated patients, with the CBZ elimination half-life
      set to 13.7 h to account for enzymatic autoinduction. The model was then used to
      simulate plasma CBZ concentrations when a dose is taken 3, 6, or 9 h late, or
      when two doses are taken at one time. RESULTS: Predicted plasma CBZ
      concentrations in this simulation fell from a trough of approximately 6.4
      microg/ml only to 4 microg/ml after 24 h without medication, and only to 2.5
      microg/ml after 36 h without medication. Predicted plasma CBZ concentrations in
      this simulation never rose above 9 microg/ml, indicating that taking missed doses
      of CBZ-ERC as soon as remembered, up to two missed doses 3 h before taking the
      next scheduled dose, will not lead to harmful spikes in plasma concentrations of
      CBZ. CONCLUSIONS: The simulations suggest that taking a missed dose of CBZ-ERC as
      soon as remembered, up to two doses at one time, may be the best strategy to
      return plasma CBZ concentrations to steady-state levels. Since the model used in
      this study is a simplified model of a highly complex situation, caution should be
      used when relating these results to clinical practice until trials are conducted
      in patients.

PMID- 14594525
TI  - 'Real-life burden of depression' surveys--GP and patient perspectives on
      treatment and management of recurrent depression.
AB  - Depression is a chronic, recurrent illness carrying a heavy burden for the health
      service and the community. Current evidence suggests that the majority of
      patients with depression will experience recurrent episodes of illness, although
      there is extensive evidence that continuation therapy with antidepressant drugs
      will prevent relapse. Two surveys were designed and distributed in the UK in 2002
      to compare the expectations of patients and GPs in the management of relapse in
      depression. For the patient survey, 1010 completed questionnaires of the 7000
      distributed (through the charity Depression Alliance), were returned for analysis
      and feedback. For the GP survey (endorsed by the charity Primary care Mental
      Health Education (PriMHE), 200 responses were received from the 400 GPs
      contacted. A majority of patients in the survey (85%) who experience depression
      expressed concern about recurrent episodes and 88% of respondents had suffered at
      least one repeat episode. The survey found that 65% of respondents had stopped
      taking their medication at some stage: reasons cited include unacceptable side
      effects and lack of efficacy. The findings suggest that discontinuation and non
      compliance of therapies is associated with recurrent depression. Continuation
      therapy is now standard treatment to avoid recurrent depression; however, the
      majority of GPs questioned, continued therapy for less than the 6 months after
      acute treatment response as advised by the British Associated of
      Psychopharmacologists. Although depression is generally managed well at primary
      care level, this survey highlights the major worries of depression sufferers
      concerning further episodes of depression and the need to prevent relapse and
      recurrence through safe and effective therapies with which these patients are
      happy to comply.

PMID- 14594526
TI  - Effects of pioglitazone on metabolic control and blood pressure: a randomised
      study in patients with type 2 diabetes mellitus.
AB  - AIM: This Swiss multicentre study examined the efficacy and safety of oral
      pioglitazone in patients with type 2 diabetes. METHODS: Patients were randomised
      to pioglitazone at once-daily doses of 30 mg for 20 weeks (n = 76), 30 mg for 12
      weeks followed by 45 mg for 8 weeks (n = 74), or 45 mg for 20 weeks (n = 84);
      94.9% of patients completed 12 weeks and 88.9% completed all 20 weeks. Almost all
      (96.6%) patients received pioglitazone in combination with other anti-diabetic
      treatments. RESULTS: Mean HbA(1c) at baseline was 8.8 +/- 1.2%, and changes to
      endpoint were -1.1 +/- 1.1%, -1.1 +/- 1.4% and -0.9 +/- 1.6%, respectively for
      the three dose groups ( p < 0.001 for each group). Triglyceride concentrations
      decreased in each group and the overall mean change during the study was -0.58
      mmol/l (p < 0.001 versus baseline). HDL-cholesterol increased, with an overall
      mean change of 0.10 mmol/l (p < 0.001 versus baseline). Blood pressure decreased
      from baseline, particularly for hypertensive patients with mean changes: systolic
      -10 mmHg, p < 0.001, diastolic -8 mmHg, p < 0.001 versus baseline. Serum alanine
      aminotransferase and gamma-glutamyl transferase concentrations were significantly
      (p < 0.001 for each) reduced during the study. CONCLUSIONS: The study
      demonstrates the efficacy of pioglitazone 30 mg/day and 45 mg/day in the
      treatment of type 2 diabetes, with an improved lipid profile and decreased blood
      pressure in addition to improved glycaemic control.

PMID- 14594527
TI  - Early vascular benefits of statin therapy.
AB  - Large-scale trials established that statin administration in
      hypercholesterolaemic individuals and patients with coronary heart disease (CHD)
      significantly reduces the risk of vascular events and death. This benefit was
      primarily attributed to their actions on lipids. This review focuses on the
      benefits (clinical and experimental) of statins observed soon (approximately 12
      weeks) after their administration. Statins rapidly increase nitric oxide
      production and improve endothelial function (e.g. increased flow-mediated
      dilatation). Similarly, antioxidant properties decrease the susceptibility of low
      density lipoprotein cholesterol to oxidation. Statins inhibit the migration of
      macrophages and smooth muscle cell proliferation leading to an antiproliferative
      effect and the stabilisation of atherosclerotic plaques. Anti-inflammatory
      effects include a reduction in serum C-reactive protein levels, inflammatory and
      proinflammatory cytokines (e.g. IL-6, IL-8), adhesion molecules (e.g. ICAM-1,
      VCAM-1) and other acute phase proteins. Statins influence the haemostatic system.
      They reduce tissue factor expression and platelet activity, whereas fibrinolysis
      can be enhanced. Statins improve microalbuminuria, renal function, hypertension
      and arterial wall stiffness. A significant reduction of the carotid intima media
      thickness (IMT) was also reported early after statin treatment. These early
      effects of statins probably contribute to the significant reduction in vascular
      events seen in some 'short-term' studies. There is a need to further elucidate
      the rapid and non-lipid lowering properties of statins.

PMID- 14594528
TI  - Chemokines: key players in cancer.
AB  - Chemokines are a family of low molecular weight (8-10 kDa) pro-inflammatory
      cytokines, which bind to G-protein coupled receptors. Their primary function is
      chemoattraction and activation of specific leucocytes in various immuno
      inflammatory responses. However, new research suggests that they are key players
      in cancer being involved in the neoplastic transformation of cells, promotion of
      aberrant angiogenesis, tumour clonal expansion and growth, passage through the
      extracellular matrix (ECM), intravasation into blood vessels or lymphatics and
      the non-random homing of tumour metastasis to specific sites. In view of the
      increasing significance of chemokines and their receptors in cancers of a variety
      of types, manipulation of this signalling pathway may be important in the
      development of new anticancer agents. This review provides an overview of recent
      research advances in this field and examines the potential therapeutic benefits
      future developments may bring.

PMID- 14594529
TI  - Low molecular weight heparin (nadroparine) versus oral anticoagulant
      (acenocoumarol) in the long-term treatment of deep venous thrombosis: comparison
      of efficacy, safety and hospitalisation period in 105 patients.
AB  - OBJECTIVE: To evaluate and compare the efficacy and safety of low molecular
      weight heparin (LMWH) (nadroparine) and acenocoumarol in the treatment of deep
      venous thrombosis (DVT). METHODS: A retrospective study of the case notes of 105
      patients (68 men) with established DVT who had been hospitalised during a 6-year
      period in a university hospital department. RESULTS: Among 105 patients, 65
      received nadroparine and the remaining intravenous unfractionated heparin (UH) as
      initial treatment. Twenty-seven patients out of 65 continued their treatment with
      nadroparine and the remaining 78 patients (38 initially treated with LMWH and 40
      with UH) with acenocoumarol. The average hospital stay for those on LMWH
      treatment was 2.2 +/- 1.4 days in comparison to 6.4 +/- 1.2 days for those
      treated with acenocoumarol (p < 0.001). During the home-based phase of treatment,
      14 patients were re-admitted to hospital for recurrent DVT; ten and four of those
      treated with acenocoumarol and LMWH, respectively (p = NS). Haemorrhagic
      complications occurred in 12 of the patients who received acenocoumarol and in
      one of those on LMWH (p = NS). CONCLUSIONS: The patients who received LMWH had a
      significantly lower duration of hospitalisation than those who received
      acenocoumarol. There were no significant differences between the administration
      of LMWH and acenocoumarol in terms of efficacy or safety in patients with DVT.

PMID- 14594530
TI  - Internal mammary sentinel nodes in primary breast cancer.
AB  - For over a century, there has been considerable interest in the management of
      regional lymph node metastasis in patients with primary breast cancer. Since the
      advent of sentinel lymph node biopsies, there has been renewed interest in the
      management of patients with metastasis to the internal mammary nodes. The
      appropriate management of these patients has not yet been established. Some
      investigators propose that biopsy of the internal mammary sentinel node may
      provide additional prognostic information which might be used to guide the
      administration of systemic adjuvant therapy. Additionally, it has been suggested
      that patients with metastasis to the internal mammary sentinel node may benefit
      from radiotherapy to the internal mammary nodal chain. Clinical trials are needed
      to resolve these issues. Internal mammary sentinel node biopsy in patients with
      primary breast cancer should be considered investigational, and conducted only in
      the context of clinical trials.

PMID- 14594531
TI  - British women's choice between sentinel node biopsy and axillary node clearance
      for breast cancer.
AB  - BACKGROUND: Recent studies have demonstrated that the sentinel node biopsy (SNB),
      which utilises a simple principle, is a reliable and minimally invasive method
      for determining the status of the regional lymph nodes in patients with
      clinically node-negative breast cancer. The technique is increasingly being used
      in the management of patients with early breast cancer despite the lack of long
      term data from randomised controlled trials which are currently in progress.
      However, increasing numbers of breast cancer patients are specifically requesting
      SNB in order to avoid axillary nodal clearance (ANC) if the sentinel node is
      negative for malignancy. The aim of this study is to determine the proportion of
      female patients attending a breast unit who would choose the SNB in preference to
      ANC. METHODS: A detailed questionnaire, based on a utility analysis and
      containing clear and precise information on arm morbidity associated with ANC (1
      in 10) versus a potential reduction in the 5-year-survival rate with SNB (1 in
      1000) was distributed to 200 female patients attending the Princess Grace
      Hospital Breast Unit (London, UK) during January 2003. The questionnaire
      consisted of two possible treatment scenarios (ANC or SNB) for early-stage breast
      cancer with their associated risks and benefits, and participants were asked to
      choose one of the two options. RESULTS: A total of 200 completed questionnaires
      were received. Out of the 200 women, 99 (49.5%) chose the SNB option and 101
      (50.5%) chose the ANC option. There is no significant relationship between the
      option made with a woman's age (mean age: 53.4 vs 54), family history of breast
      cancer (p = 0.118), personal history of breast cancer (p = 0.85), or employment
      status (p = 0.96). CONCLUSION: This study demonstrates that a high level of
      acceptance exists among women for SNB as an alternative to ANC as the preferred
      treatment of early breast cancer, despite the risk involved. As this exciting
      technique continues to evolve and improve, it is hoped that more women will be
      given the choice to opt for this treatment and that eventually SNB may completely
      replace ANC as the standard treatment for early breast cancer.

PMID- 14594532
TI  - Arris & Gale lecture. Regulation and responses of gallbladder muscle activity in
      health and disease.
AB  - A complex relationship links biliary symptoms with the mechanisms of gallbladder
      emptying and the presence of gallstones. This relationship has been investigated
      by clinical studies of symptoms associated with gallstones, by investigation of
      gallbladder emptying and cholecystokinin (CCK) release in patients with
      gallstones, and after cholecystectomy, or truncal vagotomy, and in the irritable
      bowel syndrome (IBS). Laboratory studies examined receptor density on bovine
      gallbladder, and contractility of human gallbladder in response to a variety of
      stimuli was studied in vitro. A set of six symptoms associated with the presence
      of gallstones was identified; IBS appeared to be present in two-fifths of
      patients before cholecystectomy but only one-third of these patients had
      persistent IBS symptoms one year after operation. Gallbladder emptying studies
      confirmed the poor contraction of stone-bearing gallbladders; abnormal patterns
      of emptying were also found in patients with IBS. Gallbladder emptying and
      filling appear to be largely neurally regulated. CCK receptor density was very
      low in gallbladder tissue, suggesting that receptors on nerve cells might mediate
      the action of CCK. Relaxation of gallbladder muscle was mediated by adrenergic
      and nitrergic nerves. The inflammatory mediator bradykinin, however, had a strong
      direct action on muscle cells to cause gallbladder contraction. The work reported
      here gives an overview of the symptoms and mechanisms of disease associated with
      the presence of stones in the gallbladder.

PMID- 14594533
TI  - A survey of the timing and approach to the surgical management of cholelithiasis
      in patients with acute biliary pancreatitis and acute cholecystitis in the UK.
AB  - BACKGROUND: Recent management guidelines and randomised clinical trials have
      provided evidence-based guidance to the management of acute biliary pancreatitis
      and acute cholecystitis. METHODS: A questionnaire was sent to the 1086 members of
      the Association of Surgeons of Great Britain and Ireland. There were 583
      responders (54%). RESULTS: A policy of cholecystectomy during the index admission
      or within 4 weeks in fit patients recovering from mild acute biliary pancreatitis
      was adopted by 58% of surgeons, and was significantly associated with an upper
      gastrointestinal and hepato-pancreato-biliary subspecialty interest and a volume
      of more than 50 cholecystectomies per annum (OR, 0.43; 95% CI, 0.26-0.72; P =
      0.001: and OR, 0.46; 95% CI, 0.29-0.74; P = 0.001, respectively). A policy of
      urgent cholecystectomy for acute cholecystitis was adopted by 20% of surgeons,
      and was significantly associated with an upper gastrointestinal/hepato-pancreato
      biliary subspecialty interest and the 'routine' adoption of laparoscopic approach
      to cholecystectomy (OR, 0.34; 95% CI, 0.19-0.60; P < 0.001: and OR, 0.51; 95% CI,
      0.3-0.86; P = 0.01, respectively). CONCLUSIONS: The management of cholelithiasis
      in patients with acute biliary pancreatitis in the UK remains suboptimal.
      Moreover, only a minority of surgeons offer patients presenting with acute
      cholecystitis the benefits of early laparoscopic cholecystectomy. The management
      of acute biliary disease may be improved if these cases were concentrated in the
      hands of surgeons with upper gastrointestinal/hepato-pancreato-biliary interest
      and those who perform laparoscopic cholecystectomy regularly.

PMID- 14594534
TI  - Conservative treatment as an option in the management of pancreatic pseudocyst.
AB  - BACKGROUND: Management of pancreatic pseudocysts is associated with considerable
      morbidity (15-25%). Traditionally, pancreatic pseudocysts have been drained
      because of the perceived risks of complications including infection, rupture or
      haemorrhage. We have adopted a more conservative approach with drainage only for
      uncontrolled pain or gastric outlet obstruction. This study reports our
      experience. PATIENTS AND METHODS: A consecutive series of 36 patients with
      pancreatic pseudocysts were treated over an 11-year period in one district
      general hospital serving a population of 310,000. This study group comprised of
      19 men and 17 women with a median age of 55 years (range, 10-88 years). Twenty
      two patients had a preceding attack of acute pancreatitis whilst 12 patients had
      clinical and radiological evidence of chronic pancreatitis. The aetiology
      comprised of gallstones (16), alcohol (5), trauma (2), tumour (2),
      hyperlipidaemia (1) and idiopathic (10). RESULTS: All patients were initially
      managed conservatively and intervention, either by radiological-assisted external
      drainage or cyst-enteric drainage (by surgery or endoscopy), was only performed
      for persisting symptoms or complications. Patients treated conservatively had 6
      monthly follow-up abdominal ultrasound scans (USS) for 1 year. Fourteen of the 36
      patients (39%) were successfully managed conservatively, whilst 22 patients
      required intervention either by percutaneous radiological drainage (12), by
      endoscopic cystogastrostomy (1) or by open surgical cyst-enteric anastomosis (9).
      Median size of the pancreatic pseudocysts in the 14 patients managed
      conservatively (7 cm) was nearly similar to that of the 22 patients requiring
      intervention (8 cm). The most common indications for invasive intervention in the
      22 patients were persistent pain (16), gastric outlet obstruction (4), jaundice
      (1) and dyspepsia with weight loss (1). Although one patient required surgery for
      persistent pain, no other patients required urgent or scheduled surgery for
      complications of untreated pancreatic pseudocysts. Two of the 12 patients treated
      by percutaneous radiological drainage had recurrence of pancreatic pseudocysts
      requiring surgery. Two patients developed an intra-abdominal abscess following
      cyst-enteric drainage of pancreatic pseudocysts and one patient had a pulmonary
      embolism. On the mean follow-up of 37.3 months, one patient with alcoholic
      pancreatitis died 5 months after surgical cyst-enteric bypass. CONCLUSIONS: These
      results suggest that many patients with pancreatic pseudocysts can be managed
      conservatively if presenting symptoms can be controlled.

PMID- 14594535
TI  - Post-cholecystectomy benign biliary stricture with portal hypertension: is a
      portosystemic shunt before hepaticojejunostomy necessary?
AB  - BACKGROUND: Portal hypertension develops in 15-20% of patients with benign bile
      duct stricture. Hepaticojejunostomy in such patients is associated with
      considerable morbidity and mortality. Preliminary portosystemic shunting has been
      suggested to reduce intra-operative bleeding. We present our experience without
      preliminary shunting in such patients. PATIENTS AND METHODS: Fourteen consecutive
      cases of biliary stricture with portal hypertension over a 13-year period (1989
      2001) were retrospectively analysed. RESULTS: Thirteen patients were operated
      upon. One patient had a preliminary portosystemic shunt. In another patient,
      shunt was attempted. One stage hepaticojejunostomy was possible in 11 patients.
      There were no intra-operative deaths. Nine of the 13 survived and were available
      for follow-up. One patient had cholangitis. Another had jaundice related both to
      chronic liver disease and a strictured hepaticojejunostomy. The remaining 7
      patients are asymptomatic and anicteric although alkaline phosphatase levels
      remain elevated in 5 of them. CONCLUSIONS: Hepaticojejunostomy without
      preliminary portosystemic shunting is possible in patients with portal
      hypertension and benign biliary stricture with acceptable morbidity and mortality
      rates.

PMID- 14594536
TI  - A 10-year serial, prospective study of laparoscopic cholecystectomy training in a
      single region.
AB  - AIM: To determine how surgical registrar training in laparoscopic cholecystectomy
      evolved in a single region in the 10 years since the introduction of this
      technique. METHODS: In 1993, 1996, and 2001, identical, standardised postal
      questionnaires were sent to all general surgical registrars in the Oxford region.
      The questionnaire enquired about the number of laparoscopic cholecystectomies
      performed, performed with supervision or simply assisted at within a set time
      period. RESULTS: There has been a significant increase in the number of
      procedures performed by trainees between 1993 and 2000, in comparison to the
      number purely assisted at. CONCLUSIONS: After an initial learning period for the
      consultant trainers, laparoscopic cholecystectomy has been rapidly adopted, and
      is now a major training operation, much as open cholecystectomy was in the past.

PMID- 14594537
TI  - Laparoscopic surgery in children.
AB  - A review of laparoscopy as used in paediatric surgery with special reference to
      cholecystectomy, appendicectomy, fundoplication, the undescended testicle,
      inguinal hernia and hydroceles.

PMID- 14594538
TI  - Who is doing laparoscopic appendicectomies and who taught them?
AB  - BACKGROUND: Laparoscopic appendicectomy offers potential advantages, but its use
      seems variable and perhaps related to the enthusiasm of individual trainees.
      There is limited opportunity in many hospitals for consultants to do and teach
      laparoscopic appendicectomy because of the way emergency work is organised.
      METHODS: This study investigated the use and teaching of laparoscopic
      appendicectomy in two health regions, by a questionnaire sent to all specialist
      registrars (SpRs) in general surgery and completed by 78% (56 of 72). RESULTS: Of
      the responding SpRs, 43% had performed a laparoscopic appendicectomy (with an
      average of 2.5 supervised by a consultant and 7.5 with a more junior assistant).
      Of these, 92% had been taught by a consultant, but only 31% (33 of 108) of the
      consultants for whom they were currently working had done appendicectomy
      laparoscopically, and laparoscopic appendicectomy was only being performed on 14%
      of the SpRs current firms (47% with upper gastrointestinal and 40% with
      colorectal specialist interest). Some 5-30% of patients on those firms were
      treated laparoscopically, mostly at the preference of the SpR. CONCLUSIONS:
      Dedicated consultant time for emergencies would facilitate teaching of
      laparoscopic appendicectomy but theatre time, costs of disposable instruments,
      and the inexperience of many consultants in this operation are likely to continue
      limiting its use. Further debate is needed on its place in the treatment of
      appendicitis.

PMID- 14594539
TI  - Liver resection for colorectal metastases.
AB  - BACKGROUND: Colorectal cancer is the second commonest malignancy in the UK.
      Metastases to the liver occur in greater than 50% of patients and remain the
      biggest determinant of outcome in these patients. Liver resection is a safe
      procedure that achieves good long-term survival, but surgery has traditionally
      been limited to select groups of patients. The improved outcome suggests that
      more patients could benefit from resection if more was known of what criteria are
      predictive of a good outcome. PATIENTS AND METHODS: A retrospective analysis was
      performed on all patients undergoing surgical resection of the liver for
      colorectal metastases between March 1989 and March 2001 in the Birmingham Liver
      Unit. RESULTS: During this period, 212 liver resections for colorectal cancer
      metastases were performed in 82 females and 130 males. The median follow-up was
      16 months with an overall actuarial survival of 86% at 1 year, 54% at 3 years,
      and 28% at 5 years. The peri-operative mortality was 2.8%. The number and timing
      (metachronous or synchronous) of metastatic lesions, the gender of the patient,
      pathological staging of the primary lesion or surgical resection margins had no
      significant influence on survival. Patients with lesions less than 5 cm in size
      had a significantly prolonged survival compared with patients with lesions
      greater than 5 cm in size (P < 0.004). CONCLUSIONS: Liver resection is the only
      curative treatment for patients with colorectal metastases. The long-term
      survival reported in patients with resected colorectal metastases confined to the
      liver is comparable to primary surgery for solid gastrointestinal tumours. Every
      attempt must be made to increase the availability of liver resection to patients
      with hepatic metastases from colorectal cancer.

PMID- 14594540
TI  - Morbidity associated with surgical treatment of ureteric calculi in a teaching
      hospital in Kuwait.
AB  - BACKGROUND: Ureteric lithiasis is a common urological problem in Kuwait. Because
      of the different interventional approaches, we carried out an audit on the
      morbidity associated with the surgical management of the disorder. PATIENTS AND
      METHODS: The surgical records were reviewed of all patients with the diagnosis of
      ureteric lithiasis that were managed surgically by ureteroscopy or
      ureterolithotomy in Mubarak Al-Kabeer Hospital in Kuwait between January 1996 and
      December 1999. Patients' bio-data, location of calculi, indications for surgical
      intervention, types of therapeutic interventions, operating surgeon and
      complications were analysed. Patients managed primarily and successfully by
      extracorporeal shockwave lithotripsy were excluded from this analysis. RESULTS: A
      total of 1383 patients with ureteric calculus were managed in the period under
      review--775 (56%), 567 (41%), and 41 (3%) patients were managed by extracorporeal
      shockwave lithotripsy, ureteroscopy and ureterolithotomy, respectively. The 608
      patients managed by ureteroscopy or ureterolithotomy had a total of 710
      operations. The commonest surgical procedure performed was ureteroscopy with
      Dormia basket with or without double 'J' stenting and this accounted for 418
      (58.9%) operations. The least common procedure was ureteric meatotomy with Dormia
      basket and with or without double 'J' stenting in 9 (1.3%) patients. The overall
      complication rate was 110 out of 710 (15.5%) operations. Of the complications,
      101 (92%) were minor (e.g. haematuria, fever, and mucosal injury). Nine (8%)
      complications were major complications (e.g. ureteric perforation and ureteric
      avulsions). Ureterolithotomy and ureteroscopy with intracorporeal lithotripsy
      were associated with the highest complication rates. CONCLUSIONS: This analysis
      has shown that with technological advances, the treatment of ureteric lithiasis
      has improved and major complications have decreased. However, with so many
      therapeutic options to choose from, there is a need to audit the various
      therapeutic options and select those associated with the least morbidity rates in
      each urology unit.

PMID- 14594541
TI  - A prospective audit of the implementation of the 2-week rule for assessment of
      suspected urological cancers.
AB  - INTRODUCTION: All urology departments are under considerable pressure to comply
      with the UK Government's implementation of the 2-week rule for suspected cancer
      referrals. A prospective audit was planned to begin 6 months after introduction
      of cancer referral guidelines and a central data collection process, to
      investigate the local workload generated by these referrals, and compliance with
      the 2-week rule. METHODS: Data were collected prospectively over an 8-week
      period. All referral letters were examined by an independent urologist for any of
      the criteria defined by the regional tumour working group as suspicious of
      urological cancer. For suspected cancer referrals, the patient journey was
      followed to assess efficiency of the referral process. Results were compared with
      figures for '2-week rule' referrals for the Trust obtained from the UK Department
      of Health (DoH) website. RESULTS: In all, 234 GP referrals were reviewed, 82
      fitting regional criteria for suspected cancer. Of these, (i) 13% were either
      marked urgent with a clear statement of 'cancer' or included a clear request to
      be seen within 2 weeks; (ii) 23% included no implication of cancer; (iii) 72%
      were seen in haematuria clinic, median time to clinic visit being 56.5 days, none
      complying with the 2-week rule; and (iv) of referrals not seen in haematuria
      clinic, median time to clinic was 21 days, with 34% compliance. With more
      stringent definitions of a cancer referral, DoH figures for the Trust recorded
      just 18 referrals over 3 months, with 89% compliance. DISCUSSION: GP referral
      letters meeting guidelines for suspected cancer often failed to imply or mention
      this. Compliance with the 2-week rule was poor, especially for the haematuria
      clinic. This is variably attributable to wording of GP letters, communication
      issues, and the sheer load of patients to be seen. CONCLUSION: DoH criteria for
      cancer referrals grossly underestimate the true magnitude of workload demanded of
      the service.

PMID- 14594542
TI  - The record of in-training assessments (RITAs) in urology: an evaluation of
      trainee perceptions.
AB  - AIMS: To evaluate the effect of the Calman reforms on SpRs in urology with
      respect to their educational goals, their experience of the RITA process and its
      value in preparing them for their chosen consultant careers. PARTICIPANTS AND
      METHODS: All urological trainees holding national training numbers who had
      completed at least one RITA review, but had not yet been awarded a CCST, were
      sampled. RESULTS: A total of 100 completed replies were received. Of those
      replying, 87% had an appointed educational supervisor with marked variation
      between regions. Training expectations in the four main categories of knowledge,
      vocational skills, operative competencies and personal development for each
      particular year of training were clear to only 40%, 35%, 44% and 60% of trainees,
      respectively. In general, trainee satisfaction with their most recent RITA review
      was fair with a mean of 6 (range, 4-8) on an arbitrary 10-point scale. Of the
      trainees, 83% felt that they would be adequately trained for consultant practice
      at the end of their training although this confidence varied between years of
      training. CONCLUSIONS: Unification in the registrar grade has initiated an
      improvement in urological education for SpRs. There has, however, been haphazard
      delivery of that education due to a lack of objectivity in definition and
      assessment of the educational goals in individual training years. The RITA
      process should be more prescriptive in its administration and the setting of
      annual targeted training objectives should help to optimise the training
      opportunities for individual SpRs.

PMID- 14594543
TI  - The impact of violent injuries on an NHS plastic surgery unit.
AB  - BACKGROUND: Violence and injuries caused by violence appear to be increasing.
      PATIENTS AND METHODS: A prospective study of violent injuries treated in our
      unit. RESULTS: Over a 5-month period, 148 (21%) of 704 acute admission patients
      aged 14 years or more and 11 children had injuries due to violence. The head,
      neck and hands were the commonest sites of injury. Of the 148 patients, 144 (91%)
      underwent surgery for their injuries. CONCLUSIONS: Injuries due to violence have
      a significant effect on the resources of our NHS hospital and probably of all NHS
      hospitals with acute surgical services.

PMID- 14594544
TI  - Surface wound healing: a new, general function of eukaryotic cells.
AB  - The ability to repair surface wounds is a property, necessary for long-term
      survival, expressed to various extents by all eukaryotic cell types except
      erythrocytes. The process is based on the rapid Ca(2+)-induced exocytosis of
      various types of specific organelles, such as lysosomes and enlargeosomes, that
      decreases surface tension and makes possible the spontaneous fusion of lipid
      monolayers at the lesion edges. The recognized importance of the process in
      physiology and in several cases of pathology is discussed.

PMID- 14594545
TI  - Patching the membranes up - new views on cellular healing.

PMID- 14594546
TI  - Cyclooxygenase-2 modulates cellular growth and promotes tumorigenesis.
AB  - Cyclooxygenase (COX)-2 and the prostaglandins resulting from its enzymatic
      activity have been shown to play a role in modulating cell growth and development
      of human neoplasia. Evidence includes a direct relationship between COX-2
      expression and cancer incidence in humans and animal models, increased
      tumorigenesis after genetic manipulation of COX-2, and significant anti-tumor
      properties of non-steroidal anti-inflammatory drugs in animal models and in some
      human cancers. Recent data showed that COX-2 and the derived prostaglandins are
      involved in control of cellular growth, apoptosis, and signal through a group of
      nuclear receptors named peroxisome proliferator-activated receptors (PPARs). In
      this article we will review some of the findings suggesting that COX-2 is
      involved in multiple cellular mechanisms that lead to tumorigenesis.

PMID- 14594547
TI  - Protein folding.
AB  - The problem of protein folding is that how proteins acquire their native unique
      three-dimensional structure in the physiological milieu. To solve the problem,
      the following key questions should be answered: do proteins fold co- or post
      translationally, i.e. during or after biosynthesis, what is the mechanism of
      protein folding, and what is the explanation for fast folding of proteins? The
      two first questions are discussed in the current review. The general lines are to
      show that the opinion, that proteins fold after they are synthesized is hardly
      substantiated and suitable for solving the problem of protein folding and why
      proteins should fold cotranslationally. A possible tentative model for the
      mechanism of protein folding is also suggested. To this end, a thorough analysis
      is made of the biosynthesis, delivery to the folding compartments, and the rates
      of the biosynthesis, translocation and folding of proteins. A cursory attention
      is assigned to the role of GroEL/ES-like chaperonins in protein folding.

PMID- 14594548
TI  - Genetic-dependency of peroxisomal cell functions - emerging aspects.
AB  - This paper reviews aspects concerning the genetic regulation of the expression of
      the well studied peroxisomal genes including those of fatty acid beta-oxidation
      enzymes; acyl-CoA oxidase, multifunctional enzyme and thiolase from different
      tissues and species. An important statement is PPARalpha, which is now long known
      to be in rodents the key nuclear receptor orchestrating liver peroxisome
      proliferation and enhanced peroxisomal beta-oxidation, does not appear to control
      so strongly in man the expression of genes involved in peroxisomal fatty acid
      beta-oxidation related enzymes. In this respect, the present review strengthens
      among others the emerging concept that, in the humans, the main genes whose
      expression is up-regulated by PPARalpha are mitochondrial and less peroxisomal
      genes. A special emphasis is also made on the animal cold adaptation and on need
      for sustained study of peroxisomal enzymes and genes; challenging that some
      essential roles of peroxisomes in cell function and regulation still remain to be
      discovered.

PMID- 14594549
TI  - Regulation of apoptosis by Bcl-2 family proteins.
AB  - For multicellular organisms, the rigorous control of programmed cell death is as
      important as that of cell proliferation. The mechanisms involved in the
      regulation of cell death are not yet understood, but a key component is the
      family of caspases which are activated in a cascade and are responsible for the
      apoptotic-specific changes and disassembly of the cell. Although the caspases
      represent a central point in apoptosis, their activation is regulated by a
      variety of other factors. Among these, Bcl-2 family plays a pivotal role in
      caspases activation, by this deciding whether a cell will live or die. Bcl-2
      family members are known to focus much of their response to the mitochondria
      level, upstream the irreversible cellular damage, but their functions are not yet
      well defined. This review summarizes the recent data regarding the Bcl-2 proteins
      and the ways they regulate the apoptosis.

PMID- 14594550
TI  - A new look at the cellular scaffold by embedment-free electron microscopy method.
AB  - The basic scaffold of most cells is afforded by the cytoskeleton (comprising
      microfilaments, intermediate filaments and the microtubules). The conventional
      methods of electron microscopy fail to visualize filamentous cell structure. They
      can show only these filaments lying at the section surface. Heavy metal staining
      (I), and the optical properties of the resins used for embedding are similar to
      those of proteins hence most proteinaceous structures remain unresolved and the
      cytoplasm seems to be quite homogenous (II). Aldehyde fixation could cross-link
      proteins and lead to the emergence of artificial structures (III). These
      limitations may be overcome by the use of the embedment-free electron microscopy
      (EF-EM). This technique present cellular scaffold as a purified, isolated, three
      dimensional network with various thickness of filaments. Our study on the dynamic
      aspect of cellular scaffold indicate that the thickness and arrangement of
      filaments depend on cell type and both physiological or pathological
      environments. Thank also to the adaptation of immunocytochemistry to EF-EM it was
      possible to understand the nuclear matrix and cytomatrix structure in relation to
      function. Thus, combination these methods revealed findings suggesting the
      nuclear homing of proapoptotic proteins and their association with intermediate
      filaments.

PMID- 14594551
TI  - Catalytic antibodies in healthy humans and patients with autoimmune and viral
      diseases.
AB  - Antibodies have been first characterized as proteins produced by the immune
      system solely for binding other molecules, called antigens, with the goal of
      eliciting immune response. In this classical conception, antibodies act similarly
      to enzymes in specific binding to different molecules but cannot catalyze their
      chemical conversion. However, in 1986 the first monoclonal catalytic antibodies
      against a chemically stable analog of the transition state of a reaction were
      obtained and termed abzymes (Abzs). At present, artificial monoclonal Abzs
      catalyzing more than 100 distinct chemical reactions have been obtained. The
      discovery of IgG specifically hydrolyzing intestinal vasoactive peptide in the
      blood serum of asthma patients stimulated studies of natural Abzs. Numerous Abzs
      discovered afterwards in sera of patients with various autoimmune diseases, viral
      disorders, or in the milk of healthy mothers, are capable of hydrolyzing
      proteins, DNA, RNA, polysaccharides, or nucleotides, as well as to phosphorylate
      proteins and lipids. The phenomenon of catalysis by auto-Abzs is more and more in
      research focus. In this review we summarize new data on Abzs applications in
      basic science, medicine and biotechnology.

PMID- 14594552
TI  - Attenuation of changes in G(i)-proteins and adenylyl cyclase in heart failure by
      an ACE inhibitor, imidapril.
AB  - Cardiac dysfunction in animals with congestive heart failure due to myocardial
      infarction (MI) is known to be associated with a wide variety of defects in
      receptor and post-receptor mechanisms. Since the heart function have been shown
      to be improved by treatment with different angiotensin converting enzyme (ACE)
      inhibitors, we examined the effects of imidapril, an ACE inhibitor, on changes in
      post-receptor mechanisms involving adenylyl cyclase (AC) and G proteins in the
      failing heart. Heart failure in rats was induced by occluding the coronary artery
      and 3 weeks later the animals were treated daily with 1 mg/kg (orally) imidapril
      for 5 weeks. The animals were assessed for their left ventricular function and
      crude membranes were isolated from the viable left ventricle and examined for AC
      activities as well as G-protein activities and expression. Animals with heart
      failure exhibited depressions in ventricular function and AC activities in the
      absence or presence of forskolin, NaF and Gpp(NH)p. The AC activity in the
      presence of pertussis toxin was increased whereas that in the presence of cholera
      toxin was decreased in the failing heart. Protein contents and mRNA levels for
      G(i)-proteins were increased whereas those for G(s)-proteins were unaltered in
      the infarcted heart. All these changes due to MI were prevented by imidapril
      treatment. The results indicate that the depressed cardiac function in the
      failing heart may partly be due to the direct effects of changes in AC and G(i)
      proteins.

PMID- 14594553
TI  - Correlation between the predicted and the observed biological activity of the
      symmetric and nonsymmetric cyclic urea derivatives used as HIV-1 protease
      inhibitors. A 3D-QSAR-CoMFA method for new antiviral drug design.
AB  - The predicted inhibition constant (Ki) and the predicted inhibitor concentration
      (IC90) of the HIV-1 protease (HIV- 1 PR) inhibitors: symmetric and nonsymmetric -
      benzyl, ketone, oxime, pyrazole, imidazole, and triazole cyclic urea derivatives,
      were obtained by the 3D-CoMFA (Comparative Molecular Field Analysis) method. The
      CoMFA statistical parameters: cross-validate correlation coefficient (q2), higher
      than 0.5, and the fitted correlation coefficient (r2), higher than 0.90 validated
      the predicted biological activities. The best predictions were found for the
      trifluoromethyl ketoxime derivative (log 1/Ki predict = 8.42), the m-pyridineCH2
      pyrazole derivative (log 1/Ki predict = 9.77) and the 1,2,3 triazole derivative
      (log 1/Ki predict = 7.03). We attempted to design a new potent HIV-1 protease
      inhibitor by addition of o-benzyl to the (p-HOPhCH2) pyrazole 12f derivative
      inhibitor. A favorable steric area surrounded the o-benzyl, suggesting a possible
      new potent HIV-1 protease inhibitor.

PMID- 14594554
TI  - Somatotroph to thyrotroph cell transdifferentiation during experimental
      hypothyroidism - a light and electron-microscopy study.
AB  - Somatotroph and thyrotroph pituitary cells share a common precursor cell
      expressing the transcription factor Pit1 in ontogeny. Cells expressing both
      thyrotropin (TSH) and growth-hormone (GH) are found in adult rat pituitary and in
      human pituitary adenomas in acromegaly, and these tumors contain both thyrotropin
      releasing hormone (TRH) and the TRH receptors (TRHR). It has been shown that
      stimulation of TSH expression in primary hypothyroidism promotes changes
      suggestive of somatotroph to thyrotroph cell transdifferentiation. We tested this
      hypothesis and the role of TRH in experimental primary hypothyroidism in rats.
      Adult female Long-Evans rats, 6 months old, were administered the antithyroid
      drug methimazole (0.1% w/v) in the drinking water for 42 days. Animals were
      sacrificed by perfusion fixation under anaesthesia at weekly intervals and
      pituitary tissue processed in acrylic resin for immunofluorescence and immuno
      electronmicroscopy for TSH, GH and TRHR. In the hypothyroid rat pituitary
      immunofluorescent somatotrophs were greatly reduced in number and gradually
      replaced by thyrotrophs during methimazole administration. Colocalization of GH
      and TSH in the same cell was noted. Immunoelectronmicroscopy demonstrated the
      development of enlarged thyrotrophs with dilated rough endoplasmic reticulum
      containing an electron-dense material and intracisternal granules, both of which
      are immunoreactive for TSH ('thyroidectomy cells'). The somatotrophs showed
      reduced GH immunoreactivity and also the presence of TSH-type, small-size
      secretory granules. This suggests that the greatly increased number of TSH-cells
      in methimazole-induced-hypothyroidism is due, at least partially, to the
      transdifferentiation of somatotroph into thyrotroph cells. TRHR
      immunofluorescence was expressed in many somatotrophs in normal rat pituitary and
      unlike immunoreactive GH, its expression was enhanced during hypothyroidism. The
      number of TRHR-immunoreactive cells increased in parallel with the number of TSH
      immunoreactive cells. This indicates a role for TRH stimulation in the
      transdifferentiation process. Taken together, these data suggest that, in
      addition to the cell mutation mechanism involving an early totipotential
      progenitor cell, transdifferentiation of existing somatotroph cells also plays a
      part in the pathogenesis of multihormonal GH-secreting adenomas.

PMID- 14594555
TI  - Relationship of tobacco smoking with GSTM1 gene polymorphism in laringeal cancer.
AB  - This paper aimed to analyze the association of polymorphism of GSTM1 0/0 genotype
      with laryngeal cancer along a hospital based case-control study. Polymorphisms of
      GSTM1 0/0 of samples from 36 patients with laryngeal cancer and 35 healthy
      controls were detected by PCR method. The reaction used as GSTM1 primers, using
      the sequence sense: 5'-CTGCCCTACTTGGATTGATGGG-3' and antisense: 5'
      TGGATTGTAGCAGATCATGC-3'. N Acetyl transferase 1 (NAT1) gene using the primers
      sense: 5'-TAAAAGTAAAATGATTTGCTTTCG-3' and antisense: 5'- GCTTTCTAGCATAAATCACCAA
      3' was used as internal positive control. Two sided 2 and multivariation analysis
      were used to analyse the results. The proportions of GSTM1 deleted genotype in
      cases and controls were 47.2% and 54.3%, respectively. There was significant
      increment of GSTM 0/0 genotype frequency in moderate smokers group of patients
      compared to control (P=0.033, OR= 4.78, 95% CI = 1.30-7.13). We conclude that
      GSTM1 deleted genotype may be a genetic susceptibility marker for laryngeal
      cancer whose exposed to low doses carcinogens. The absence of this enzyme seems
      to have a role in the development of laryngeal cancer, in which the mechanism
      still needs further investigation.

PMID- 14594556
TI  - Apoptotic rate in patients with myelodisplastic syndrome treated with modulatory
      compounds of pro-apoptotic cytokines.
AB  - Excessive apoptosis has a central role in ineffective hematopoiesis in
      myelodysplastic syndrome (MDS). The aim of the study was to quantify apoptosis
      and Bcl-2 expression in patients with MDS and to use these parameters in the
      evaluation of treatment efficacy with compounds modulating proapoptotic
      cytokines. Bone marrow (BM) samples from eight MDS patients were studied: four
      with refractory anemia and four with refractory anemia with ringed sideroblasts.
      Two patients with Hodgkin disease without BM determination were studied for
      control. Therapy consisted in administration of pentoxyphylline, dexamethasone
      and ciprofloxacin. Biochemical assay of apoptosis and Bcl-2 was performed using
      annexin V-biotin conjugate antibody and anti-human Bcl-2 antibody respectively,
      followed by streptavidine-peroxidase conjugate, and peroxidase substrate.
      Ultrastructural investigation of BM samples was performed with standard electron
      microscopy techniques. Most of BM hematopoietic cells in the MDS patients had
      ultrastructural features of various stages of apoptosis including chromatin
      condensation and margination, cytoplasm condensation and budding of nuclear and
      plasma membranes to produce apoptotic bodies. Bcl-2 expression showed an inverse
      correlation with the rate of the apoptotic process. Periodic evaluation of these
      two parameters has shown an increase of Bcl-2 expression and a decrease of
      apoptotic rate in patients who had responded to the treatment. Response to the
      treatment was appreciated in accordance with their transfusion needs. Treatment
      efficiency diminished in time. The rate of apoptosis was inversely correlated
      with the level of Bcl-2 expression. These results confirm the importance of the
      apoptotic process evaluation in monitoring MDS treatment.

PMID- 14594557
TI  - Effect of chromium picolinate on histopathological alterations in STZ and
      neonatal STZ diabetic rats.
AB  - Earlier studies from our laboratory have indicated insulin sensitizing action of
      chromium picolinate as the mechanism of its anti-diabetic activity in
      experimental models of type I and type II diabetes. In the present investigation,
      we have evaluated the effects of chronic administration of chromium picolinate on
      the functional and histological alterations of streptozotocin (STZ)-induced
      diabetes in rats. Type I diabetes was induced by intravenous injection of STZ (40
      mg/kg) in adult rats, whereas, type II diabetes was induced by intraperitoneal
      injection of STZ (90 mg/kg) in 2-day old rat pups which in adulthood develop
      abnormalities resembling type II diabetes. Chromium picolinate was administered
      at 8 microg/ml in drinking water for 6 weeks and was found to improve glucose
      tolerance and increase insulin sensitivity of STZ-diabetic rats. This treatment
      decrease elevated serum creatinine and urea levels as well as elevated serum
      levels of hepatic enzymes of both groups of diabetic rats. Histopathological
      studies of kidney and liver show decrease in the intensity and incidence of
      vacuolations, cellular infiltration and hypertrophy of STZ and nSTZ (neonatal
      STZ) diabetic rats. Chronic treatment with chromium picolinate however, did not
      alter the normal function or morphology of control rats. Chronic chromium
      picolinate at the therapeutic doses that improved glucose tolerance, was observed
      to have no hepatotoxic or nephrotoxic potential. It was rather found to improve
      renal and hepatic function and to reduce abnormalities associated with STZ
      diabetes. Chromium picolinate could play an important role in the long term
      management of diabetes mellitus.

PMID- 14594558
TI  - Membrane blebbing and apoptotic bodies in cerebellar cells.

PMID- 14594559
TI  - QSAR - a piece of drug design.

PMID- 14594560
TI  - EUROCORES on the development of a stem cell tool box.

PMID- 14594561
TI  - Clinical trials report. Metabolic modulation as a principle for myocardial
      protection.

PMID- 14594562
TI  - Circadian rhythms in cardiac gene expression.
AB  - Circadian rhythms in blood pressure, heart rate, and cardiac output have been
      intensely studied, largely due to the well-documented phenomenon of increased
      cardiovascular death in the early hours of the morning. Circadian rhythmicity in
      both cardiovascular physiology and pathophysiology has been attributed primarily
      to diurnal variations in neurohumoral factors, such as sympathetic activity. It
      has become increasingly apparent that the intrinsic properties of the heart (seen
      at the level of gene and protein expression, energy metabolism, and contractile
      function) show significant fluctuations during the course of the day. These
      changes might be due to extracardiac (eg, neurohumoral factors) and/or
      intracardiac (eg, circadian clocks) influences. Circadian clocks are
      transcriptionally based, molecular mechanisms that enable the cell to anticipate
      diurnal variations in environmental stimuli. The cardiac circadian clock
      synchronizes responsiveness of the heart to diurnal variations in its
      environment, and impairment of this mechanism might contribute to the
      pathogenesis of cardiovascular disease.

PMID- 14594563
TI  - Transcriptional regulation of energy substrate metabolism in normal and
      hypertrophied heart.
AB  - Impaired myocardial energy metabolism in cardiac hypertrophy and failure is
      characterized by decreased fatty-acid oxidation and increased glucose
      utilization. Mechanisms involving deactivation of peroxisome proliferator
      activated receptor alpha/relinoid X receptor alpha (PPARalpha/RXRalpha),and
      activation of chicken ovalbumin upstream promoter transcription factor (COUP-TF),
      and transcription factors Sp1 and Sp3, lead to decreased capacity for fatty acid
      utilization in hypertrophied hearts. Furthermore, impaired myocardial energetic
      status stimulates glucose uptake and glycolysis, which, in combination with the
      permissive effect due to decreased fatty acid oxidation, promotes increases in
      glucose utilization in hypertrophied hearts. Finally, shifting substrate
      utilization toward glucose is likely adaptive and has the potential to delay
      transition to heart failure.

PMID- 14594564
TI  - The Role of AMP-activated protein kinase in fuel selection by the stressed heart.
AB  - The heart responds to energetic stress with both acute and chronic changes in
      substrate metabolism. Recent work has demonstrated that the metabolic stress
      kinase AMP-activated protein kinase (AMPK) plays an important role in the acute
      regulation of carbohydrate and fatty acid metabolism in the setting of acute
      energetic stressors, such as ischemia/reperfusion, or increased workload, through
      covalent and noncovalent regulation of enzymes involved in intermediary
      metabolism. In addition, chronic activation of AMPK has been shown to affect the
      expression of key proteins regulating carbohydrate and fatty acid metabolism.
      Characterizing the effects of AMPK will provide important insights into its
      function in the normal heart and might provide new metabolic therapies for
      ischemic heart disease and heart failure.

PMID- 14594565
TI  - Metalloproteinases and plasminogen activators in vessel remodeling.
AB  - Remodeling of blood vessels underlies the pathogenesis of major cardiovascular
      disorders, including atherosclerosis, restenosis, and hypertension. Because
      remodeling of arteries is highly dependent on degradation of the extracellular
      matrix, which enables cells to migrate and proliferate, there is intense interest
      in the regulation and the roles of matrix metalloproteinases (MMPs) and the
      plasminogen activator-plasmin (PA-P) systems in vessel remodeling. Factors that
      promote vessel remodeling have been shown to be important in upregulating the
      activities of both proteolytic systems and include chronic changes in
      hemodynamics, vessel injury, cytokines involved in inflammation, and elevations
      in reactive oxygen species. The two proteolytic systems utilize common
      transcription factors to activate their respective genes and are frequently
      coexpressed in remodeling and atherosclerotic arteries. In this review, we
      discuss the effects of activating the MMP and PA-P systems on processes involved
      in vascular remodeling, factors regulating their expression and activation, their
      roles in restenosis, and the development and progression of atherosclerosis, as
      well as the ability of currently available inhibitors to prevent unfavorable
      remodeling and atherosclerosis.

PMID- 14594566
TI  - Endothelial nitric oxide synthase and endothelial dysfunction.
AB  - Nitric oxide (NO) regulates vascular tone and local blood flow, platelet
      aggregation and adhesion, and leukocyte-endothelial cell interactions.
      Abnormalities in NO production by the vascular endothelium result in endothelial
      dysfunction, which occurs in hypertension, diabetes, aging, and as a prelude to
      atherosclerosis. The common feature of endothelial dysfunction is a decrease in
      the amount of bioavailable NO. In this article, the physiologic roles of NO and
      the mechanisms of endothelial dysfunction are reviewed. Regulation of endothelial
      NO synthase (eNOS) activity by fatty acid modifica-tions, intracellular
      localization, interactions with heat shock protein 90 (hsp90) and caveolin,
      substrate and cofactor dependence, and phosphorylation might all affect the level
      of bioavailable NO. A hypothesis is proposed that the final common pathway of
      diverse causes of endothelial dysfunction involves abnormalities in eNOS
      phosphorylation at Ser 1179 and other key phosphorylation sites.

PMID- 14594568
TI  - Calcium channel blockers (felodipine) and pediatric essential hypertension.

PMID- 14594567
TI  - Clinical trials report. Risks and benefits of hormone replacement therapy.

PMID- 14594569
TI  - Management of hypertension emergencies.
AB  - Although they have become less common, hypertensive emergencies occur with an
      incidence of approximately 1 to 2/100,000 people per year. Our knowledge about
      this problem, its pathophysiology, risk factors, and appropriate treatment
      options has expanded during the past decade. A hypertensive emergency can be
      declared when an elevated blood pressure is associated with acute target-organ
      damage. Rapid evaluation and treatment (typically with an intravenously
      administered agent) should be instituted, usually in an intensive care unit
      setting, and the patient should be observed carefully during acute blood-pressure
      lowering. When properly treated, the prognosis for these patients is not nearly
      as dismal as it was more than 60 years ago, and the initial level of function of
      target organs (brain, heart, kidneys) is more indicative of an emergency than the
      actual level of blood pressure. Therapeutic options include the time-tested
      sodium nitroprusside (which has toxic metabolic products and is contraindicated
      in pregnancy, tobacco amblyopia, and Leber's optic atrophy); fenoldopam mesylate;
      and nicardipine. When properly treated, "malignant hypertension" need be
      considered malignant no longer.

PMID- 14594570
TI  - Pathophysiology of pre-eclampsia: update on the role of nitric oxide.
AB  - Women with chronic hypertension and pregnancy-induced hypertension are at
      substantial risk for developing pre-eclampsia/eclampsia, a disease with high
      fetomaternal morbidity and mortality. However, the etiology of this disease is
      still unknown. In this article, recent concepts on the pathophysiology of pre
      eclampsia, with special attention to the role of nitric oxide, are reviewed.

PMID- 14594571
TI  - Hypertension and adrenal disorders.
AB  - Adrenal disorders causing hypertension can be related to the dysfunction of
      either the adrenal cortex or the adrenal medulla. These disorders, including
      congenital adrenal hyperplasia (CAH), owing to 11B-hydroxylase deficiency and to
      17alpha-hydroxylase deficiency; apparent mineralocorticoid excess; familial
      hyperaldosteronism type I; primary aldosteronism; Cushing's syndrome; and
      familial glucocorticoid resistance, primarily affect the adrenal cortex and cause
      low-renin hypertension. The classic disorder of the adrenal medulla resulting in
      hypertension is pheochromocytoma, although hypertension in obesity might also be
      associated with catecholamine secretion. In this review, we discuss these
      etiologies and the most recent advances in our knowledge of their
      pathophysiology, diagnosis, and treatment.

PMID- 14594574
TI  - Palisaded neutrophilic and granulomatous dermatitis.
AB  - A 46-year-old man with a history of systemic lupus erythematosus presented with a
      6-month history of scaly, erythematous, tender nodules on his elbows and hands.
      Physical examination showed erythematous, umbilicated papules, with crusts on the
      elbows and the dorsa of the hands. Histopathologic examination demonstrated
      leukocytoclastic vasculitis with dense neutrophilic infiltrates and degenerated
      collagen, consistent with early palisaded neutrophilic and granulomatous
      dermatitis. The individual lesions were treated with intralesional glucocorticoid
      injections with some improvement.

PMID- 14594575
TI  - Metastatic calcification.
AB  - Calciphylaxis is a rare, painful, and debilitating disease of widespread
      metastatic calcification that progresses to ischemic tissue necrosis. It occurs
      almost exclusively in patients with end-stage renal disease and secondary
      hyperparathyroidism. Reticulated, violaceous, mottled patches commonly appear on
      the lower extremities and progress to cordlike nodules and necrotic ulcers with
      overlying eschars. Septicemia, which may occur after secondary infection of the
      ulcers, is the most common cause of death. Treatment with phosphate-binding
      antacids, total or partial parathyroidectomy, and avoidance of local tissue
      trauma remain the mainstays of therapy, although a uniform cure for calciphylaxis
      remains elusive. Prognosis for patients with calciphylaxis is dismal, even after
      surgical intervention. Early diagnosis and treatment is critical to prevent
      progression of the disease process.

PMID- 14594572
TI  - Impact of female hormones on blood pressure: review of potential mechanisms and
      clinical studies.
AB  - In recent studies, it has been found that postmenopausal hormonal therapy is
      associated with an increased incidence of cardiovascular disease. Experimental
      studies suggest several potential mechanisms by which estrogens might decrease
      blood pressures, and estrogen administration attenuates hypertension in several
      animal models. In humans, although oral contraceptive agents are frequently
      associated with increases in blood pressure, blood pressure was not increased or
      was minimally increased in prospective clinical trials of hormone therapy in
      postmenopausal women. These observations suggest that the excess rates of
      cardiovascular disease are not caused by increased blood pressure.

PMID- 14594573
TI  - Thyroid hormone and blood pressure regulation.
AB  - Thyroid hormone has well-recognized effects on the cardiovascular system and
      blood pressure regulation. Blood pressure is altered across the entire spectrum
      of thyroid disease. The effects of hyperthyroidism include increased cardiac
      output, contractility, tachycardia, widened pulse pressure, decreased systemic
      vascular resistance, and increased basal metabolic rate. The manifestations of
      hypothyroidism are in marked contrast to those of hyperthyroidism and include
      decreased cardiac output, narrow pulse pressure, increased systemic vascular
      resistance, and decreased metabolic rate. Although thyroid hormone affects almost
      all tissues of the body and mediates changes in homeostasis, adaptations of the
      cardiovascular system can result in changes in blood pressure to accommodate the
      new demands on the system. In this paper, we review the direct and indirect
      thyroid hormone-mediated effects on blood pressure.

PMID- 14594576
TI  - Relapsing polychondritis.
AB  - A 57-year-old man presented with a 2-year history of (1) recurrent swelling of
      the ears that spared his earlobes and (2) migratory arthralgias. A biopsy
      specimen of the ear showed a perichondrial infiltrate of lymphocytes, plasma
      cells, and a few neutrophils. There were acellular foci of underlying cartilage.
      Relapsing polychondritis is characterized by recurrent inflammation and eventual
      destruction of cartilaginous tissues, primarily affecting the ears, nose,
      respiratory tract, and eyes. The condition, which is associated with autoimmunity
      against type II collagen, has a chronic, relapsing-and-remitting course that can
      be life-threatening. Treatments include a variety of anti-inflammatory and anti
      neutrophilic agents, and the prognosis is variable and depends on which organ
      systems are involved and the response to therapy.

PMID- 14594577
TI  - Annular epidermolytic ichthyosis.
AB  - A 21-year-old woman presented to the Charles C. Harris Skin and Cancer Pavilion
      with a life-long history of palmoplantar keratoderma that was accompanied by
      episodic flares of polycyclic psoriasiform patches diffusely over the rest of her
      body. A biopsy specimen of a representative skin lesion showed epidermolytic
      hyperkeratosis. The particular phenotype that this patient exhibited has been
      reported in only seven families previously in the literature. Mutations in
      keratin 1 and 10 have been identified in these patients and are similar to those
      mutations in patients with classic epidermolytic hyperkeratosis.

PMID- 14594578
TI  - Erythrokeratodermia variabilis.
AB  - A 47-year-old woman presented with both transient, figurate, erythematous patches
      and fixed, hyperkeratotic plaques on the upper extremities. Her cutaneous disease
      began in childhood and affects numerous siblings and her daughter. Her clinical
      presentation, history, and histopathologic analysis were consistent with
      erythrokeratodermia variabilis, which is a genodermatosis linked to mutations in
      the gene encoding for the gap-junction protein, connexin 31.

PMID- 14594579
TI  - Pityriasis rubra pilaris.
AB  - Pityriasis rubra pilaris is a chronic, papulosquamous dermatosis of unclear
      etiology. The case of a 61-year-old man with pityriasis rubra pilaris is
      presented. The clinical forms, histopathologic features, and treatment options of
      pityriasis rubra pilaris are reviewed.

PMID- 14594580
TI  - Psoriasis confined to the nails.
AB  - A case is presented of a 49-year-old man with psoriasis limited to the nails for
      12 years. The patient had no evidence of psoriasis elsewhere. He had been treated
      with a year-long course of griseofulvin and 2 months of weekly fluconazole
      without effect before the diagnosis of psoriasis was made by biopsy of the
      lateral nail fold. Options for the treatment of nail psoriasis are reviewed.

PMID- 14594581
TI  - Dermatitis herpetiformis.
AB  - Dermatitis herpetiformis is a chronic, lifelong disease characterized both by
      symptomatic, characteristic skin lesions and by a gluten-sensitive, often
      asymptomatic, enteropathy. Cutaneous findings include intensely pruritic vesicles
      on symmetrical extensor locations. Treatment for disease may be pharmacologic
      agents or a gluten-free diet. Evidence for the genetic basis of disease has been
      elucidated.

PMID- 14594582
TI  - Familial multiple lipomatosis.
AB  - Familial multiple lipomatosis is a rare hereditary syndrome with a proposed
      autosomal-dominant inheritance. A case of an 89-year-old man with this disease is
      presented, along with his pedigree. Clinical features, genetic evidence, and
      treatment options are reviewed.

PMID- 14594583
TI  - Frontal linear scleroderma (en coup de sabre).
AB  - En coup de sabre is a type of linear scleroderma that presents on the frontal or
      frontoparietal scalp. The case of a 54-year-old woman with a 3 and one-half year
      history of en coup de sabre is presented. The clinical presentation, laboratory
      findings, epidemiology, etiologic hypotheses, and treatment options are reviewed.

PMID- 14594584
TI  - Scleroderma.
AB  - A 72-year-old man with diabetes-associated scleredema is presented. The patient
      had a long history of diabetes mellitus that had been difficult to control with
      complications of retinopathy, nephropathy, and arteriosclerosis leading to
      myocardial infarcts and stroke. The scleredema has remained stable with 4 months
      of topical clobetasol ointment twice daily and biweekly physical therapy.
      Diseases associated with scleredema and therapeutic options are summarized.

PMID- 14594585
TI  - Pachyonychia congenita, type II.
AB  - A 5-year-old girl presented with extensor hyperkeratotic papules and subungual
      hyperkeratosis with nail-plate discoloration affecting all twenty nails. The
      mother reported that her daughter had natal teeth. By report, the father has a
      similar history and constellation of clinical findings. The patient's clinical
      presentation and history was consistent with pachyonychia congenita, which is a
      genodermatosis linked to mutations in the genes encoding keratins 6, 16, and 17.

PMID- 14594586
TI  - Generalized granuloma annulare.
AB  - Granuloma annulare is an inflammatory condition that is primarily idiopathic, but
      it has been associated with certain diseases, most notably diabetes mellitus.
      Lesions usually resolve, but resolution is less likely to occur with diffuse
      disease. This case report presents a patient with diffuse granuloma annulare.
      Recent advances in pathogenesis and treatment options are discussed.

PMID- 14594587
TI  - Eruptive syringoma.
AB  - Eruptive syringoma is a rare eruption of small, flesh-colored papules that occurs
      in successive crops on the anterior body surfaces and arises in the peripubertal
      period. The lesions are benign, and treatment options are generally
      unsatisfactory. The case of a 27-year-old man with a 1-year history of eruptive
      syringoma is presented.

PMID- 14594588
TI  - Inflammatory linear verrucous epidermal nevus.
AB  - Inflammatory verrucous epidermal nevus presents in early childhood as a pruritic,
      erythematous, linear plaque. The 23-year-old man described in this report
      demonstrates the adult onset of the condition. Clinical findings, differential
      diagnosis, disease associations, and treatment options are discussed.

PMID- 14594589
TI  - Cushing syndrome secondary to topical glucocorticoids.
AB  - An 11-year-old boy with a history of psoriasis presented with Cushingoid
      stigmata, which included weight gain, central obesity, violaceous striae, and
      facial plethora. It was discovered that he had used potent topical
      glucocorticoids for two months prior to the onset of his weight gain. Laboratory
      studies were consistent with adrenal suppression that improved after
      discontinuation of the use of topical glucocorticoids.

PMID- 14594590
TI  - Purpura annularis telangiectodes of Majocchi.
AB  - A case is presented of a man with a 3-year history of ulcers in the setting of
      pigmented, annular and purpuric lesions of the lower extremities. A skin biopsy
      suggested a diagnosis of purpura annularis telangiectodes of Majocchi. First
      described in 1896 by Majocchi [1], purpura annularis telangiectodes is an
      uncommon pigmented purpuric eruption, which is characterized by symmetrical,
      purpuric, telangiectatic, and atrophic patches with a predilection for the lower
      extremities and buttocks. Histopathology and immunopathogenesis of this disease
      are similar to the other subtypes of pigmented purpuric dermatoses.

PMID- 14594591
TI  - Steatocystoma multiplex.
AB  - A 25-year-old man with a 20-year history of asymptomatic nodules on his arms and
      trunk, which histopathological analysis showed to be consistent with
      steatocystoma multiplex, is presented. Steatocystoma multiplex is a disorder
      characterized by multiple, asymptomatic, dermal cysts that usually occur on the
      trunk and proximal aspects of the extremities. Steatocystoma multiplex with acral
      predominance has only recently been described. Development of steatocystomas has
      been hypothesized to be due to alterations in the structure of keratin 17.
      Treatment for lesions has included surgical excision or drainage, oral retinoids,
      and liquid nitrogen cryotherapy.

PMID- 14594592
TI  - Bullous pemphigoid and psoriasis vulgaris.
AB  - A 55-year-old man with psoriasis presented with erythematous, edematous plaques,
      tense bullae, and erosions. Direct immunofluorescence and histopathologic
      examination confirmed the diagnosis of bullous pemphigoid. Both dermatologic
      conditions responded to azathioprine. The clinical presentation, etiology, and
      treatment options are reviewed.

PMID- 14594593
TI  - Melanoma-associated leukoderma.
AB  - A case is presented of a man with a history of melanoma treated with sentinel
      lymphadenectomy and interferon therapy, who subsequently developed diffuse
      hypopigmented patches thought to be consistent with a diagnosis of melanoma
      associated leukoderma. Clinically, melanoma-associated leukoderma is a diffuse
      macular hypomelanosis or depigmentation, which often develops at sites distant to
      the location of the primary melanoma. The leukoderma may be hypomelanotic and
      mottled or depigmented and milk-white. Spontaneous repigmentation may occur. A
      recent study has demonstrated that T cells involved in the destruction of
      neoplastic melanocytes are identical clones of those that accumulate in melanoma
      associated leukoderma.

PMID- 14594594
TI  - Progressive and symmetric erythrokeratoderma.
AB  - A case of progressive and symmetric erythrokeratoderma in a 9-year-old boy is
      presented. The evidence for loricrin as a candidate gene for this disorder as
      well as the clinical features of this disease are reviewed.

PMID- 14594596
TI  - Mycosis fungoides.
AB  - The case of a 46-year-old woman with poikiloderma vasculare atrophicans is
      discussed. It is a rare clinical form of patch-stage mycosis fungoides
      characterized by generalized poikiloderma, atrophy, mottled dyspigmentation, and
      telangiectases.

PMID- 14594595
TI  - Disseminated cutaneous granulomatous eruption occurring in the setting of
      myelodysplasia.
AB  - A 66-year-old woman with a myelodysplastic syndrome developed a widespread,
      pruritic, nodular eruption. A skin-biopsy specimen showed a granulomatous
      infiltrate, with no evidence of clonality; a bone-marrow biopsy showed possible
      transition to acute myeloid leukemia. This presentation is consistent with two
      prior reports of granulomatous eruptions occurring in the setting of
      myelodysplasia.

PMID- 14594597
TI  - Generalized morphea.
AB  - A 69-year-old man presented with symmetric erythematous, hyperpigmented, and
      ivory-colored plaques on the trunk and extremities. His clinical history,
      laboratory analysis, and histopathologic examination were consistent with
      generalized morphea, a subtype of localized scleroderma.

PMID- 14594598
TI  - Erythema dyschromicum perstans and vitiligo.
AB  - We report an East Indian man with simultaneous lesions of erythema dyschromicum
      perstans and vitiligo. This report is only the second to present these two
      pigmentary disorders occurring in the same patient. Although the exact cause of
      both disorders is unknown, a pathogenetic role for cytotoxic T-cell responses has
      been hypothesized in each condition.

PMID- 14594599
TI  - Segmental neurofibromatosis.
AB  - Segmental neurofibromatosis is a rare variant of neurofibromatosis in which skin
      lesions are confined to a circumscribed body segment. A case of a 72-year-old
      woman with this condition is presented. Clinical features and genetic evidence
      are reviewed.

PMID- 14594601
TI  - Sweet syndrome.
AB  - Sweet syndrome is characterized by fever, leukocytosis, and tender, erythematous,
      well-demarcated papules and plaques, which show dense neutrophilic infiltrates
      and papillary dermal edema. It may occur in the absence of other diseases but is
      often associated with malignant conditions and may be induced by various
      medications. Treatment with systemic glucocorticoids generally is successful but
      may require prolonged courses to suppress recurrences.

PMID- 14594600
TI  - Aquagenic syringeal acrokeratoderma.
AB  - A case of a 32-year-old woman with aquagenic syringeal acrokeratoderma is
      presented. This case is the eleventh to report this condition. As with previously
      reported cases, the condition presents in young women and results in edema of the
      palms with visibly prominent eccrine ducts after brief exposure to water. The
      patient responded to aluminum chloride applied topically. Prior cases are
      reviewed.

PMID- 14594602
TI  - Foreign-body reaction with Mycobacterium abseccus superinfection.
AB  - Mycobacterium abscessus is a rare cause of skin and soft tissue infections that
      often results from inoculation with contaminated foreign material. A 41-year-old
      woman is described regarding an outbreak of M. abscessus following soft tissue
      augmentation. Clinical features and treatment options are reviewed.

PMID- 14594603
TI  - Palmoplantar keratoderma of Sybert.
AB  - A 13-year-old boy and a 7-year-old boy, who are brothers, presented with a life
      long history of erythema, hyperkeratosis, and desquamation of the hands and feet.
      Symptoms improved with the use of topical glucocorticoids and keratolytics. PPK
      of Sybert is characterized by palmoplantar hyperkeratosis with transgrediens,
      autosomal dominant inheritance, and the absence of associated systemic features.

PMID- 14594604
TI  - Klippel-Trenaunay syndrome.
AB  - A 28-year old woman with extensive right-leg capillary malformation associated
      with limb hypertrophy and limb-length discrepancy consistent with Klippel
      Trenaunay syndrome is presented. Treatment with the new long-pulsed-dye lasers
      may lead to improvement of the superficial hemangioma component of the affected
      areas.

PMID- 14594605
TI  - Cutis verticis gyrata.
AB  - An 82-year-old man had deep, linear skin folds on the scalp. The patient did not
      have a history of neuropsychiatric disorders and was generally in good health
      except for diabetes mellitus, hypertension, and benign positional vertigo. Cutis
      verticis gyrata is a term used to describe the appearance of deep, linear skin
      folds in the scalp. Primary and secondary types of this condition exist. No
      treatment is typically needed, although surgical modalities may be beneficial for
      severely disfiguring types.

PMID- 14594606
TI  - Eosinophilic fasciitis.
AB  - The case of a 76-year-old woman with eosinophilic fasciitis is presented.
      Reported etiologic associations and treatment options are discussed.

PMID- 14594607
TI  - Porokeratosis plantaris, palmaris, et disseminata.
AB  - A 66-year-old woman presented with thick, hyperkeratotic papules and plaques on
      the plantar aspects of both feet as well as more superficial, annular,
      hyperkeratotic papules on the chest, neck, and face. A biopsy was consistent with
      porokeratosis. The clinical findings are consistent with porokeratosis plantaris,
      palmaris, et disseminata.

PMID- 14594608
TI  - Keratosis follicularis.
AB  - Keratosis follicularis is a genetic disorder that is inherited in an autosomal
      dominant pattern. Physical examination classically shows keratotic papules that
      are distributed mostly on the so-called "seborrheic" areas of the body. Nail
      involvement is not uncommon and is characterized by V-shaped nicking at the
      distal aspect of the nail bed, longitudinal red and white alternating bands, and
      subungual hyperkeratosis. Mucosal membrane involvement may occur as white papules
      on the buccal mucosae, palate, and gingiva with a cobblestone appearance. The
      mutation has been traced to chromosome 12, where a spectrum of mutations within
      the ATP2A2 gene encode the calcium ATPase of the sarco/endoplasmic reticulum
      (SERCA2).

PMID- 14594609
TI  - Generalized eruptive keratoacanthomas.
AB  - We describe the case of a 71-year-old-woman with a 6-year history of generalized
      eruptive keratoacanthomas on the extremities. We review the diagnostic clinical
      and histologic features of the rare Grzybowski variant of generalized eruptive
      keratoacanthoma. The course of this disease is chronic and often demonstrates a
      poor response to therapy.

PMID- 14594610
TI  - Erythema elevatum diutinum.
AB  - A 53-year-old man with human-immunodeficiency-virus infection presents with a 2
      year history of nodules on the extensor surfaces of his extremities. A biopsy
      confirmed the diagnosis of erythema elevatum diutinum. The clinical presentation,
      histopathology, etiology, and treatment options are reviewed.

PMID- 14594611
TI  - Type I hereditary punctate keratoderma.
AB  - A 75-year-old man with a history of prostatic carcinoma and atypical
      fibroxanthoma reports a long-standing history of 1-2 mm depressed, hyperkeratotic
      papules on the palms. His mother suffered a similar condition. Histologically,
      the papules demonstrated hyperkeratosis, without columns of parakeratosis. A
      diagnosis of type I hereditary punctate keratoderma (Buschke-Fisher-Brauer
      disease) was made. This condition, which is classified as one of the three
      hereditary forms of punctate palmoplantar keratoderma, is an autosomal-dominant
      condition with variable penetrance. It is characterized clinically by multiple,
      tiny, punctate keratoses of the palms and soles. Affected individuals appear to
      be at increased risk of developing malignant conditions.

PMID- 14594612
TI  - Granuloma faciale.
AB  - Granuloma faciale is characterized by indurated, red-brown papules and plaques
      that usually occur on the face. We present a 52-year-old man with typical
      clinical and histologic features of this condition. A review of treatment options
      is presented.

PMID- 14594613
TI  - Sarcoidosis.
AB  - A 54-year-old man presented with symmetric, bulbous, nodular enlargement of the
      nasal tip and alae nasi. At first inspection, the changes appeared to be
      consistent with rhinophyma, but a biopsy specimen showed noncaseating granulomata
      that were consistent with sarcoidosis. His laboratory, radiographic, and
      pulmonary function studies were consistent with systemic involvement.

PMID- 14594614
TI  - Chronic actinic dermatitis.
AB  - A 52-year-old man experienced a pruritic and erythematous eruption on his face,
      neck, upper chest, and arms. On examination his lesions consisted of edematous,
      erythematous plaques with scale and lichenified plaques. His clinical
      presentation, a skin biopsy specimen with a spongiotic dermatitis, positive patch
      and photopatch tests, and low MEDB and MEDA tests provided a diagnosis of chronic
      actinic dermatitis.

PMID- 14594615
TI  - Subcutaneous T-cell lymphoma.
AB  - A 70-year-old woman presents with a 2-year history of intermittent, subcutaneous
      nodules. The patient was otherwise asymptomatic. A biopsy specimen was consistent
      with a subcutaneous T-cell lymphoma, a rare subset of peripheral T-cell lymphoma;
      when accompanied by the hemocphagocytic syndrome, it can be rapidly fatal. The
      histopathologic characteristics and nature of the disease are discussed.

PMID- 14594616
TI  - Epidermal nevus.
AB  - A 20-year-old woman presented with an asymptomatic, life-long, verrucous,
      hyperpigmented plaque on the face and neck that corresponded to the lines of
      Blaschko. Histopathologic examination shows an epidermal nevus. This nevus
      presents a challenge in management because of the location and extent of the
      lesion.

PMID- 14594617
TI  - Oxidative stress-related mechanisms are associated with xenobiotics exerting
      excess toxicity to Fanconi anemia cells.
AB  - An extensive body of evidence has demonstrated the sensitivity of Fanconi anemia
      (FA) cells to redox-active xenobiotics, such as mitomycin C, diepoxybutane,
      cisplatin, and 8-methoxypsoralen plus ultraviolet irradiation, with toxicity
      mechanisms that are consistent with a deficiency of FA cells in coping with
      oxidative stress. A recent study has reported on excess sensitivity of FA
      complementation A group cells to chromium VI [Cr(VI)] toxicity, by postulating
      that a deficiency in Cr-DNA cross-link removal by FA cells and formation of
      Cr(VI)-associated cross-links may be the mechanism of Cr(VI)-induced
      cytotoxicity. However, the report failed to demonstrate any enhanced Cr uptake
      or, especially, any increase in Cr-DNA adducts. Thus, well-established findings
      on Cr(VI)-induced oxidative stress may explain excess sensitivity of FA cells to
      Cr(VI) in terms of its inability to cope with the Cr(VI)-induced prooxidant
      state.

PMID- 14594618
TI  - Is the decline of the increasing incidence of non-Hodgkin lymphoma in Sweden and
      other countries a result of cancer preventive measures?
AB  - Is the decline of the increasing incidence of non-Hodgkin lymphoma (NHL) in
      Sweden and other countries a result of cancer preventive measures? The yearly age
      standardized incidence of NHL increased significantly in Sweden during 1971-1990,
      for men an average of 3.2% and for women 3.1%. The corresponding figures for 1991
      2000 were -0.8% and -0.2%, respectively. A decline of the increasing incidence
      has also been seen in other countries, such as the United States, Finland, and
      Denmark. Immunosuppression is one established risk factor for NHL, possibly with
      interaction with Epstein-Barr virus. Phenoxyacetic acids and chlorophenols, both
      pesticides, have been associated with NHL. Use of these chemicals was banned in
      Sweden in 1977 and 1978, respectively. Also, persistent organic pollutants such
      as polychlorinated biphenyls, hexachlorobenzene, chlordanes, and dioxins have
      been shown to increase the risk. Exposure of the whole population occurs
      predominantly through the food chain. Exposure to such chemicals was highest in
      the 1960s and 1970s. Because of regulation in the 1970s, exposure has declined
      substantially in the population. The change in incidence of NHL in Sweden and
      other countries may serve as a good example of how prohibition and limitation of
      exposure may be reflected in cancer statistics some decades later.

PMID- 14594619
TI  - Association between essential tremor and blood lead concentration.
AB  - Lead is a ubiquitous toxicant that causes tremor and cerebellar damage. Essential
      tremor (ET) is a highly prevalent neurologic disease associated with cerebellar
      involvement. Although environmental toxicants may play a role in ET etiology and
      their identification is a critical step in disease prevention, these toxicants
      have received little attention. Our objective was to test the hypothesis that ET
      is associated with lead exposure. Therefore, blood lead (BPb) concentrations were
      measured and a lifetime occupational history was assessed in ET patients and in
      controls. We frequency matched 100 ET patients and 143 controls on age, sex, and
      ethnicity. BPb concentrations were analyzed using graphite furnace atomic
      absorption spectrophotometry. A lifetime occupational history was reviewed by an
      industrial hygienist. BPb concentrations were higher in ET patients than in
      controls (mean +/- SD, 3.3 +/- 2.4 and 2.6 +/- 1.6 microg/dL, respectively;
      median, 2.7 and 2.3 microg/dL; p = 0.038). In a logistic regression model, BPb
      concentration was associated with diagnosis [control vs. ET patient, odds ratio
      (OR) per unit increase = 1.21; 95% confidence interval (CI), 1.05-1.39; p =
      0.007]. BPb concentration was associated with diagnosis (OR per unit increase =
      1.19; 95% CI, 1.03-1.37; p = 0.02) after adjusting for potential confounders.
      Prevalence of lifetime occupational lead exposure was similar in ET patients and
      controls. We report an association between BPb concentration and ET. Determining
      whether this association is due to increased exposure to lead or a difference in
      lead kinetics in ET patients requires further investigation.

PMID- 14594620
TI  - Changing heat-related mortality in the United States.
AB  - Heat is the primary weather-related cause of death in the United States.
      Increasing heat and humidity, at least partially related to anthropogenic climate
      change, suggest that a long-term increase in heat-related mortality could occur.
      We calculated the annual excess mortality on days when apparent temperatures--an
      index that combines air temperature and humidity--exceeded a threshold value for
      28 major metropolitan areas in the United States from 1964 through 1998. Heat
      related mortality rates declined significantly over time in 19 of the 28 cities.
      For the 28-city average, there were 41.0 +/- 4.8 (mean +/- SE) excess heat
      related deaths per year (per standard million) in the 1960s and 1970s, 17.3 +/-
      2.7 in the 1980s, and 10.5 +/- 2.0 in the 1990s. In the 1960s and 1970s, almost
      all study cities exhibited mortality significantly above normal on days with high
      apparent temperatures. During the 1980s, many cities, particularly those in the
      typically hot and humid southern United States, experienced no excess mortality.
      In the 1990s, this effect spread northward across interior cities. This
      systematic desensitization of the metropolitan populace to high heat and humidity
      over time can be attributed to a suite of technologic, infrastructural, and
      biophysical adaptations, including increased availability of air conditioning.

PMID- 14594621
TI  - Prenatal exposures to phthalates among women in New York City and Krakow, Poland.
AB  - Experimental evidence has shown that certain phthalates can disrupt endocrine
      function and induce reproductive and developmental toxicity. However, few data
      are available on the extent of human exposure to phthalates during pregnancy. As
      part of the research being conducted by the Columbia Center for Children's
      Environmental Health, we have measured levels of phthalates in 48-hr personal air
      samples collected from parallel cohorts of pregnant women in New York, New York,
      (n = 30) and in Krakow, Poland (n = 30). Spot urine samples were collected during
      the same 48-hr period from the New York women (n = 25). The following four
      phthalates or their metabolites were measured in both personal air and urine:
      diethyl phthalate (DEP), dibutyl phthalate (DBP), diethylhexyl phthalate (DEHP),
      and butyl benzyl phthalate (BBzP). All were present in 100% of the air and urine
      samples. Ranges in personal air samples were as follows: DEP (0.26-7.12
      microg/m3), DBP (0.11-14.76 microg/m3), DEHP (0.05-1.08 microg/m3), and BBzP
      (0.00-0.63 microg/m3). The mean personal air concentrations of DBP, di-isobutyl
      phthalate, and DEHP are higher in Krakow, whereas the mean personal air
      concentration of DEP is higher in New York. Statistically significant
      correlations between personal air and urinary levels were found for DEP and
      monoethyl phthalate (r = 0.42, p < 0.05), DBP and monobutyl phthalate (r = 0.58,
      p < 0.01), and BBzP and monobenzyl phthalate (r = 0.65, p < 0.01). These results
      demonstrate considerable phthalate exposures during pregnancy among women in
      these two cohorts and indicate that inhalation is an important route of exposure.

PMID- 14594622
TI  - Polybrominated diphenyl ethers (PBDEs) in U.S. mothers' milk.
AB  - No previous reports exist on polybrominated diphenyl ether (PBDE) congeners in
      human milk from individual U.S. mothers. This article on PBDEs is an extension of
      our previous studies on concentrations of dioxins, dibenzofurans, polychlorinated
      biphenyls, and other chlorinated organic compounds in human milk in a number of
      countries. PBDE commercial products are used as flame retardants in flexible
      polyurethane foam (penta-BDE), in acrylonitrile-butadiene-styrene resins (octa
      BDE), and in high-impact polystyrene resins (deca-BDE). Their use is permitted in
      the United States but is banned in some European countries because of presumed
      toxicity, demonstrated persistence, and bioaccumulation. Different commercial
      products can be found in various consumer products such as television sets,
      computers, computer monitors and printers, carpets, and upholstery. Analyses of
      human levels of these compounds suggest low but rising levels in European human
      milk, which may have peaked, at least in Sweden, in the late 1990s. Very few data
      exist on levels of PBDEs in humans in the United States, and none from milk from
      individual nursing mothers. To address this issue, we analyzed 47 individual milk
      samples from nursing mothers, 20-41 years of age, from a milk bank in Austin,
      Texas, and a community women's health clinic in Dallas, Texas. Up to 13 PBDE
      congeners were measured. The concentrations of the sum of PBDE congeners varied
      from 6.2 to 419 ng/g (or parts per billion) lipid, with a median of 34 ng/g and a
      mean of 73.9 ng/g lipid. The PBDE levels in breast milk from Texas were similar
      to levels found in U.S. blood and adipose tissue lipid from California and
      Indiana and are 10-100 times greater than human tissue levels in Europe. Their
      detection in breast milk raises concern for potential toxicity to nursing
      infants, given the persistence and bioaccumulative nature of some of the PBDE
      congeners. These results indicate a need for more detailed investigation of the
      levels of PBDE in people and food, as well as determining if animal fat in food
      is the major route of exposure of the general U.S. population. Other routes of
      intake may also be significant.

PMID- 14594623
TI  - The sea urchin embryo as a model for mammalian developmental neurotoxicity:
      ontogenesis of the high-affinity choline transporter and its role in cholinergic
      trophic activity.
AB  - Embryonic development in the sea urchin requires trophic actions of the same
      neurotransmitters that participate in mammalian brain assembly. We evaluated the
      development of the high-affinity choline transporter, which controls
      acetylcholine synthesis. A variety of developmental neurotoxicants affect this
      transporter in mammalian brain. [3H]Hemicholinium-3 binding to the transporter
      was found in the cell membrane fraction at stages from the unfertilized egg to
      pluteus, with a binding affinity comparable with that seen in mammalian brain.
      Over the course of development, the concentration of transporter sites rose more
      than 3-fold, achieving concentrations comparable with those of cholinergically
      enriched mammalian brain regions. Dimethylaminoethanol (DMAE), a competitive
      inhibitor of choline transport, elicited dysmorphology beginning at the mid
      blastula stage, with anomalies beginning progressively later as the concentration
      of DMAE was lowered. Pretreatment, cotreatment, or delayed treatment with
      acetylcholine or choline prevented the adverse effects of DMAE. Because
      acetylcholine was protective at a lower threshold, the DMAE-induced defects were
      most likely mediated by its effects on acetylcholine synthesis. Transient removal
      of the hyaline layer enabled a charged transport inhibitor, hemicholinium-3, to
      penetrate sufficiently to elicit similar anomalies, which were again prevented by
      acetylcholine or choline. These results indicate that the developing sea urchin
      possesses a high-affinity choline transporter analogous to that found in the
      mammalian brain, and, as in mammals, the functioning of this transporter plays a
      key role in the developmental, trophic activity of acetylcholine. The sea urchin
      model may thus be useful in high-throughput screening of suspected developmental
      neurotoxicants.

PMID- 14594625
TI  - Arsenic exposure accelerates atherogenesis in apolipoprotein E(-/-) mice.
AB  - Epidemiologic studies have shown an association between elevated arsenic levels
      in drinking water and an increased risk of atherosclerosis and vascular diseases.
      The studies presented here were performed to evaluate the atherogenic potential
      of arsenic using a well-established and controlled animal model of human
      atherosclerosis, mice deficient in apolipoprotein E (ApoE), and in vitro systems
      including primary human vascular cells. Wild-type and ApoE-deficient mice were
      exposed to 20 or 100 microg/mL sodium arsenite in drinking water for 24 weeks. As
      assessed morphometrically, the size of grossly discernible lesions covering the
      intimal area of aorta were increased significantly in arsenic-treated ApoE
      deficient mice compared with nontreated transgenic mice. This effect was not
      associated with increased levels of serum cholesterol but was accompanied by an
      accumulation of arsenic in the vessel wall. Introduction of cocoa butter into the
      diet for 2 weeks resulted in higher serum cholesterol levels and only slight
      increases in the lesion size in control or arsenic-exposed ApoE-deficient mice.
      There were no lesions observed in the wild-type C57BL6 mice, resistant to
      atherosclerosis, whether they received arsenic or control drinking water. In
      vitro studies, including primary aorta endothelial or smooth muscle cells, were
      conducted to evaluate whether arsenic induces cellular mechanisms relevant to
      atherogenesis such as endothelial dysfunction, lipid oxidation, and smooth muscle
      cell proliferation. Arsenic treatment does not modulate endothelial cell-mediated
      lipid oxidation or smooth muscle cell proliferation but induced the expression of
      genes coding inflammatory mediators, including interleukin-8. Induction of
      endothelial inflammatory activity may play a role in arsenic-related vascular
      effects.

PMID- 14594626
TI  - Environmental, occupational, and genetic risk factors for alpha-1 antitrypsin
      deficiency.
AB  - Alpha-1 antitrypsin (AAT) deficiency is an inherited genetic disorder currently
      diagnosed in approximately 5,000 people in the United States. Although some
      individuals with AAT deficiency are asymptomatic, the condition often leads to
      deterioration of lung function in adults and is associated with emphysema,
      asthma, chronic obstructive pulmonary disease, and other respiratory diseases. In
      children, AAT deficiency can result in severe liver disease, including fatal
      cirrhosis in newborn infants. Although much is known about the clinical pathology
      of AAT deficiency, researchers are just beginning to characterize environmental,
      occupational, and genetic modifiers affecting the onset and progression of
      diseases related to AAT deficiency. On 19 August 2002, a group of basic
      scientists, clinicians, environmental health researchers, and public interest
      groups gathered at the National Institute of Environmental Health Sciences in
      Research Triangle Park, North Carolina, to discuss ongoing research on these
      topics. The goals of this workshop were to a) assess the present state of
      knowledge regarding environmental and occupational risk factors contributing to
      AAT deficiency morbidity and mortality, b) define future research needs in this
      area, and c) explore collaborative opportunities to advance understanding of risk
      factors affecting the progression of AAT deficiency-related disease. Participants
      agreed that new research initiatives in these areas represent an opportunity to
      benefit both basic science, through enhanced understanding of gene-environment
      interaction, and the AAT deficiency patient community, through innovative new
      approaches to disease management and treatment.

PMID- 14594624
TI  - Serotonergic systems targeted by developmental exposure to chlorpyrifos: effects
      during different critical periods.
AB  - During brain development, serotonin (5HT) provides essential neurotrophic
      signals. In the present study, we evaluated whether the developmental
      neurotoxicity of chlorpyrifos (CPF) involves effects on 5HT signaling, as a
      potential mechanism underlying noncholinergic neuroteratogenic events. We
      evaluated four different treatment windows ranging from the neural tube stage
      [gestational days (GD) 9-12] and the late gestational period (GD17-20) through
      postnatal phases of terminal neuronal differentiation and synaptogenesis
      [postnatal days (PN) 1-4, PN11-14]. Exposure to CPF on GD9-12 elicited initial
      suppression, immediately followed by rebound elevation, of 5HT1A and 5HT2
      receptors as well as the 5HT transporter, all at doses below the threshold for
      cholinergic hyperstimulation and the resultant systemic toxicity. In contrast,
      with GD17-20 exposure, the initial effect was augmentation of all three
      components by low doses of CPF. Sensitivity of these effects declined
      substantially when exposure was shifted to the postnatal period. We also
      identified major alterations in 5HT-mediated responses, assessed for the adenylyl
      cyclase signaling cascade. Although GD9-12 exposure had only minor effects,
      treatment on GD17-20 elicited supersensitivity to both stimulatory and inhibitory
      responses mediated by 5HT. Our results indicate that CPF affects 5HT receptors,
      the presynaptic 5HT transporter, and 5HT-mediated signal transduction during a
      discrete critical gestational window. These effects are likely to contribute to
      the noncholinergic component of CPF's developmental neurotoxicity.

PMID- 14594627
TI  - Radiographic abnormalities and exposure to asbestos-contaminated vermiculite in
      the community of Libby, Montana, USA.
AB  - Mining, handling, processing, and personal or commercial use of asbestos
      contaminated vermiculite have led to widespread contamination of the Libby,
      Montana, area. We initiated a medical testing program in response to reports of
      respiratory illness in the community. The purpose of this analysis was to
      identify and quantify asbestos-related radiographic abnormalities among persons
      exposed to vermiculite in Libby and to examine associations between these
      outcomes and participants' self-reported exposures. A cross-sectional interview
      and medical testing were conducted in Libby from July through November 2000 and
      from July through September 2001. A total of 7,307 persons who had lived, worked,
      or played in Libby for at least 6 months before 31 December 1990 completed the
      interview. Of those, 6,668 participants > or = 18 years of age received chest
      radiographs to assess the prevalence of pleural and interstitial abnormalities.
      We observed pleural abnormalities in 17.8% of participants and interstitial
      abnormalities in < 1% of participants undergoing chest radiography. We examined
      29 occupational, recreational, household, and other exposure pathways in the
      analysis. The prevalence of pleural abnormalities increased with increasing
      number of exposure pathways, ranging from 6.7% for those who reported no apparent
      exposures to 34.6% for those who reported > or = 12 pathways. The factors most
      strongly associated with pleural abnormalities were being a former W.R. Grace
      worker, being older, having been a household contact of a W.R. Grace worker, and
      being a male. In addition to being a former W.R. Grace worker, environmental
      exposures and other nonoccupational risk factors were also important predictors
      of asbestos-related radiographic abnormalities.

PMID- 14594628
TI  - Urinary biomarkers of exposure to jet fuel (JP-8).
AB  - Benzene, naphthalene, and 1- and 2-naphthol were measured in urine samples
      obtained from 322 U.S. Air Force personnel categorized a priori as likely to have
      low, moderate, or high exposure to jet fuel [jet propulsion fuel-8 (JP-8)]. In
      postexposure samples, levels of these analytes in the high-exposure group were 3-
      to 29-fold greater than in the low-exposure group and 2- to 12-fold greater than
      in the moderate-exposure group. Heavy exposure to JP-8 contributed roughly the
      same amount of benzene and more than three times the amount of naphthalene
      compared with cigarette smoking. Strong correlations were observed among
      postexposure levels of naphthalene-based biomarkers in urine and naphthalene in
      air and breath. We conclude that urinary naphthalene and the naphthols can serve
      as biomarkers of exposure to jet fuel. Of these, the naphthols are probably more
      useful because of their greater abundance and slower elimination kinetics.

PMID- 14594629
TI  - Neurobehavioral performance and work experience in Florida farmworkers.
AB  - Farmworkers experience many work-related hazards, including exposure to
      neurotoxicants. We compared neurobehavioral performance of 288 farmworkers in
      central Florida who had done farm work for at least 1 month with 51 controls who
      had not. Most of the farmworkers had worked in one or more of three types of
      agriculture: ornamental ferns, nurseries, or citrus fruit. We collected
      information on farm work history in a structured interview and evaluated
      neurobehavioral performance using a battery of eight tests. Analyses were
      adjusted for established confounders including age, sex, education, and
      acculturation. Ever having done farm work was associated with poor performance on
      four tests--digit span [odds ratio (OR) = 1.90; 95% confidence interval (CI),
      1.02-3.53], tapping (coefficient = 4.13; 95% CI, 0.00-8.27), Santa Ana test
      (coefficient = 1.34; 95% CI, 0.29-2.39), and postural sway (coefficient = 4.74;
      95% CI, -2.20 to 11.7)--but had little effect on four others: symbol digit
      latency, vibrotactile threshold, visual contrast sensitivity, and grip strength.
      Associations with farm work were similar in magnitude to associations with
      personal characteristics such as age and sex. Longer duration of farm work was
      associated with worse performance. Associations with fern work were more
      consistent than associations with nursery or citrus work. Deficits related to the
      duration of work experience were seen in former as well as current farmworkers,
      and decreased performance was related to chronic exposure even in the absence of
      a history of pesticide poisoning. We conclude that long-term experience of farm
      work is associated with measurable deficits in cognitive and psychomotor
      function.

PMID- 14594630
TI  - Association between gaseous ambient air pollutants and adverse pregnancy outcomes
      in Vancouver, Canada.
AB  - The association between ambient air pollution and adverse health effects, such as
      emergency room visits, hospitalizations, and mortality from respiratory and
      cardiovascular diseases, has been studied extensively in many countries,
      including Canada. Recently, studies conducted in China, the Czech Republic, and
      the United States have related ambient air pollution to adverse pregnancy
      outcomes. In this study, we examined association between preterm birth, low birth
      weight, and intrauterine growth retardation (IUGR) among singleton live births
      and ambient concentrations of sulfur dioxide (SO2), nitrogen dioxide (NO2),
      carbon monoxide (CO), and ozone in Vancouver, Canada, for 1985-1998. Multiple
      logistic regression was used to estimate odds ratios (ORs) and 95% confidence
      intervals (CIs) for such effects. Low birth weight was associated with exposure
      to SO2 during the first month of pregnancy (OR = 1.11, 95% CI, 1.01-1.22, for a
      5.0 ppb increase). Preterm birth was associated with exposure to SO2 (OR = 1.09,
      95% CI, 1.01-1.19, for a 5.0 ppb increase) and to CO (OR = 1.08, 95% CI, 1.01
      1.15, for a 1.0 ppm increase) during the last month of pregnancy. IUGR was
      associated with exposure to SO2 (OR = 1.07, 95% CI, 1.01-1.13, for a 5.0 ppb
      increase), to NO2 (OR = 1.05, 95% CI, 1.01-1.10, for a 10.0 ppb increase), and to
      CO (OR = 1.06, 95% CI, 1.01-1.10, for a 1.0 ppm increase) during the first month
      of pregnancy. In conclusion, relatively low concentrations of gaseous air
      pollutants are associated with adverse effects on birth outcomes in populations
      experiencing diverse air pollution profiles.

PMID- 14594631
TI  - Measurement of pesticides and other toxicants in amniotic fluid as a potential
      biomarker of prenatal exposure: a validation study.
AB  - Prenatal pesticide exposures may adversely affect children's health. However,
      exposure and health research is hampered by the lack of reliable fetal exposure
      data. No studies have been published that report measurements of commonly used
      nonpersistent pesticides in human amniotic fluid, although recent studies of
      pesticides in urine from pregnant women and in meconium indicate that fetuses are
      exposed to these chemicals. Amniotic fluid collected during amniocentesis is the
      only medium available to characterize direct fetal exposures early in pregnancy
      (approximately 18 weeks of gestation). As a first step in validating this
      exposure biomarker, we collected 100 amniotic fluid samples slated for disposal
      and evaluated analytical methods to measure organophosphate and carbamate
      pesticides and metabolites, synthetic pyrethroid metabolites, herbicides, and
      chlorinated phenolic compounds. The following six phenols were detected
      (detection frequency): 1- and 2-naphthol (70%), 2,5-dichlorophenol (55%),
      carbofuranphenol (5%), ortho-phenylphenol (30%), and pentachlorophenol (15%),
      with geometric mean concentrations of 0.72, 0.39, 0.12, 0.13, and 0.23 microg/L,
      respectively, for positive values. The organophosphate metabolites
      diethylphosphate and dimethylphosphate were detected in two (10%) samples, and
      dimethylthiophosphate was detected in one (5%) sample, with geometric mean
      concentrations of 0.31, 0.32, and 0.43 microg/L, respectively, for positive
      values. These levels are low compared with levels reported in urine, blood, and
      meconium in other studies, but indicate direct exposures to the young fetus,
      possibly during critical periods of development. Results of this pilot study
      suggest that amniotic fluid offers a unique opportunity to investigate fetal
      exposures and health risks.

PMID- 14594632
TI  - In utero exposure to di-(2-ethylhexyl)phthalate and duration of human pregnancy.
AB  - Di-(2-ethylhexyl)phthalate (DEHP), the most commonly used plasticizer in flexible
      polyvinylchloride formulations, is a ubiquitous environmental contaminant. To
      date, no information exists on the potential health hazards from exposure to DEHP
      and/or its main metabolite, mono-(2-ethylhexyl)phthalate (MEHP), in high-risk
      conditions, such as pregnancy and during the neonatal period. The aim of this
      study was to evaluate prenatal exposure to DEHP and/or MEHP and its possible
      biologic effects. We measured serum DEHP and MEHP concentrations in the cord
      blood of 84 consecutive newborns by high-performance liquid chromatography.
      Relationships between DEHP/MEHP and infant characteristics were tested using
      Fisher's exact test, unpaired t-tests, and univariate linear regression analyses,
      and significant differences on univariate analysis were evaluated using multiple
      logistic regression analysis. We found detectable cord blood DEHP and/or MEHP
      concentrations in 88.1% of the samples. Either DEHP or MEHP was present in 65 of
      84 (77.4%) of the examined samples. Mean concentrations of DEHP and MEHP were
      1.19 +/- 1.15 microg/mL [95% confidence interval (CI), 0.93-1.44, range = 0-4.71]
      and 0.52 +/- 0.61 microg/mL (95% CI, 0.39-0.66, range = 0-2.94), respectively.
      MEHP-positive newborns showed a significantly lower gestational age compared with
      MEHP-negative infants (p = 0.033). Logistic regression analysis results indicated
      a positive correlation between absence of MEHP in cord blood and gestational age
      at delivery (odds ratio = 1.50, 95% CI, 1.013-2.21; p = 0.043). These findings
      confirm that human exposure to DEHP can begin in utero and suggest that phthalate
      exposure is significantly associated with a shorter pregnancy duration.

PMID- 14594634
TI  - Qualitative methods in environmental health research.
AB  - Public health researchers increasingly turn to qualitative methods either on
      their own or in combination with quantitative methods. Qualitative methods are
      especially important to community environmental health research, as they provide
      a way to produce community narratives that give voice to individuals and
      characterize the community in a full and complex fashion. This article first
      traces the legacy of qualitative research in environmental health, then uses a
      case study of the author's experiences studying the Woburn, Massachusetts,
      childhood leukemia cluster to provide personal and scholarly insights on
      qualitative approaches. That material then informs a discussion of important
      components of qualitative methods in environmental health research, including
      flexible study design, access, trust, empathy, and personal shifts in the
      researcher's worldview, bias, and the nature of the researcher's roles. A
      concluding discussion addresses issues in funding policy and research practices.

PMID- 14594633
TI  - Ethical issues in environmental health research.
AB  - Environmental health research encompasses a wide range of investigational topics,
      study designs, and empirical methodologies. As that arm of public health research
      concerned with understanding the health effects of the many environments in which
      humans live and work, the field is intimately connected with social concerns
      about environmental quality and disparities of power and privilege that place
      differential burdens upon members of underserved communities. Environmental
      health researchers thus engage many ethical and social issues in the work they
      do. These issues relate to the choice of research topics to study, the methods
      employed to examine these topics, the communication of research findings to the
      public, and the involvement of scientific experts in the shaping of environmental
      policy and governmental regulation. These and other topics are reviewed in this
      article. These ethical, legal, and social issues are becoming increasingly more
      complex as new genetic and molecular techniques are used to study environmental
      toxicants and their potential influence on human and ecologic health.

PMID- 14594635
TI  - From general policy to legal rule: aspirations and limitations of the
      precautionary principle.
AB  - The rapid spread of the precautionary principle (PP) demonstrates the need to
      explicitly address the role of precaution in environmental decision making.
      Unfortunately, the PP in its current form is limited by the vagueness of, and
      variations in, the many formulations of the PP. This ambiguity in the meaning of
      the PP would not be so serious if the PP were limited to a general aspirational
      policy, but in every jurisdiction that has adopted the PP it has been transformed
      rapidly into a binding legal rule. As a legal rule, the ambiguity of the PP
      results in arbitrary application by regulatory agencies and reviewing courts and
      limits the capability of reviewing courts to perform their function in overseeing
      agency actions. To improve the explicit application of precaution, we must go
      beyond the current form of the PP and attempt to define the factors that weigh in
      favor of more or less precaution for specific risks.

PMID- 14594637
TI  - Public health literacy for lawyers: teaching population-based legal analysis.

PMID- 14594636
TI  - Objectivity and ethics in environmental health science.
AB  - During the past several decades, philosophers of science and scientists
      themselves have become increasingly aware of the complex ways in which scientific
      knowledge is shaped by its social context. This awareness has called into
      question traditional notions of objectivity. Working scientists need an
      understanding of their own practice that avoids the naive myth that science can
      become objective by avoiding social influences as well as the reductionist view
      that its content is determined simply by economic interests. A nuanced
      perspective on this process can improve research ethics and increase the capacity
      of science to contribute to equitable public policy, especially in areas such as
      environmental and occupational health, which have direct implications for
      profits, regulation, legal responsibility, and social justice. I discuss research
      into health effects of the 1979 accident at Three Mile Island near Harrisburg,
      Pennsylvania, USA, as an example of how scientific explanations are shaped by
      social concepts, norms, and preconceptions. I describe how a scientific practice
      that developed under the influence of medical and nuclear physics interacted with
      observations made by exposed community members to affect research questions, the
      interpretation of evidence, inferences about biological mechanisms in disease
      causation, and the use of evidence in litigation. By considering the history and
      philosophy of their disciplines, practicing researchers can increase the rigor,
      objectivity, and social responsibility of environmental health science.

PMID- 14594639
TI  - Are A-bomb survivor studies an appropriate basis for nuclear worker compensation?

PMID- 14594640
TI  - Developmental effects of herbicides in mice.

PMID- 14594642
TI  - Ethics of pesticide testing in humans.

PMID- 14594643
TI  - Mercury in Japan's whale meat.

PMID- 14594644
TI  - Toward a new understanding of aging.

PMID- 14594645
TI  - Aging research: the future face of environmental health.

PMID- 14594646
TI  - REACHing for chemical safety.

PMID- 14594647
TI  - Digital diagnosis: new tool for detecting skin cancer.

PMID- 14594649
TI  - Generalized fungal infection in a patient with AIDS appearing as skin papules.
AB  - Human immunodeficiency virus infection (HIV) is unique among cutaneous fungal
      infections caused by defects of the cell-mediated immune system. Infections with
      Candida albicans occur with increased frequency and severity among HIV-infected
      individuals. Oral candidiasis is the most common manifestation, superficial
      cutaneous infections of the dermis are rarely seen. We report a HIV-positive man
      from Cameroon presenting with generalized cutaneous papules and nodes, oral
      candidiasis, and soor esophagitis, who was successfully treated with fluconazole
      monotherapy.

PMID- 14594650
TI  - Poly ADP-ribose polymerase (PARP) inhibitors transiently protect leukemia cells
      from alkylating agent induced cell death by three different effects.
AB  - Polyadenosylation of nuclear enzymes is well known to regulate the cellular
      repair capacity after DNA damage. PARP mediates the transfer of poly-ADP-ribose
      moieties on itself and other nuclear proteins by the breakdown of NAD+. The
      present study investigated how modulation of PARP activity interferes with cell
      death induced by two different alkylating agents used in cancer chemotherapy. 1
      methyl-3-nitro-1-nitrosoguanidinium (MNNG) decreased cellular reduction capacity
      (WST-1 assay) in HL60 and CCRF-CEM cells, accompanied by increased activity of
      PARP and depletion of intracellular NAD+ and ATP. Pretreatment with the PARP
      inhibitors 3-AB or 4-AN resulted in transient cell protection, which was
      associated with a switch from necrosis to apoptosis in CCRF-CEM cells and
      enhanced apoptosis in HL60 cells. Both PARP inhibitors delayed the drop in WST-1
      reduction and retained NAD+ and ATP levels required for apoptosis. Furthermore, 3
      AB or 4-AN prevented progressive DNA degradation in MNNG-treated CCRF-CEM cells.
      In contrast to MNNG, we did not observe early activation of PARP, decrease in WST
      1 reduction, or wasteful consumption of NAD+ and ATP after treatment with
      melphalan. However, preincubation with 3-AB or 4-AN resulted in decreased HL60
      cell membrane blebbing and reduced formation of apoptotic bodies. In conclusion,
      the cell death preventing effects of PARP inhibitors are mediated by their
      ability to maintain cellular energy metabolism, to inhibit the activation of
      endonucleolytic DNA degradation and to prevent cell blebbing. Surprisingly, these
      protective effects of PARP inhibitors on different cell functions seem to be
      independent of each other and are rather determined by the respective cytotoxic
      mechanisms implicated by different drugs. Our results support the hypothesis,
      that PARP activation and/or cleavage plays a regulatory role in the induction of
      apoptosis.

PMID- 14594651
TI  - Value of ultrasound in the diagnosis of acute appendicitis: interesting aspects.
AB  - OBJECTIVE: The value of ultrasound in the diagnosis of acute appendicitis is
      still unclear. Both, studies with excellent and such with disappointing results
      have been published. The aim of this investigation was to answer the question,
      whether the results of these studies depend on study design, the investigating
      clinical department, or the number of ultrasound investigators. METHODS: A
      systematic literature research (PubMed (NLM) database) was performed. Of 99
      publications dealing with ultrasound in the diagnosis of acute appendicitis, 69
      were relevant to investigate the value of ultrasound in suspected appendicitis.
      RESULTS: Results of single-center studies (sensitivity 81.6%, specificity 89.8%,
      accuracy 85.7%) are better then those of multi-center trials (38.3%, 87.6%,
      62.9%). There are no distinct differences between the investigating departments
      (surgeons 78.9%, 88.9%, 86.0%; radiologists 83.1%, 88.1%, 83.5%; mixed 77.8%,
      87.1%, 79.4%, no specification 73.8%, 87.1%, 80.45.9%). Less than 10
      investigators showed better diagnostic values (84.3%, 86.8%, 85.6%) compared to
      studies with 10 or more investigators (64.7%, 88.6%, 67.7%). CONCLUSION: The
      results of multi-center trials are disappointing and the good results of single
      center studies do not reflect surgical everyday life. However, excellent results
      can be obtained if the investigation is restricted to a few specialists
      irrespectively of the clinical department.

PMID- 14594653
TI  - Frequency of internal derangement of the temporomandibular joint in elderly
      individuals.
AB  - Elderly patients suffer from various systemic diseases and are likely to neglect
      their problems with functional disorders in the masticatory system, which are of
      crucial importance for successful prosthetic treatment. The purpose of the study
      was to establish the frequency of symptoms, clinical signs and tissue-specific
      diagnoses of internal derangement of the temporomandibular joint in elderly
      subjects and their relation with respect to gender and type of prosthetic
      replacement. The study was conducted on 96 subjects, 48 complete denture wearers
      and 48 removable partial denture wearers, whose average age was 75.8 years. The
      diagnostic procedure used in this study was manual functional analysis consisting
      of specific techniques of dynamic compressions and translations in diagnosing
      internal derangement of the temporomandibular joint. Chi-square test for
      independent samples was used for statistical analysis of the results. The
      symptoms of internal derangement of the temporomandibular joint were found in
      9.3% of the subjects, and tissue-specific diagnoses were established in 52.1% of
      the subjects. The most common diagnoses were osteoarthrosis, total disk
      displacement with stable reposition and partial anterolateral disk displacement.
      No statistically significant differences in the frequency of symptoms, clinical
      signs and tissue-specific diagnoses were found between genders (P>.05) and
      complete and removable partial denture wearers (P>.05). The frequency of
      subjective symptoms of internal derangement in the temporomandibular joint of
      elderly subjects was low in relation to the frequency of intracapsular tissue
      specific diagnoses.

PMID- 14594652
TI  - Serum S-100B protein levels in young amateur soccer players after controlled
      heading and normal exercise.
AB  - BACKGROUND: Repeated impacts by heading might lead to significant head injuries
      in soccer players comparable to those of patients with accidental minor traumatic
      brain injury (TBI). The neuroprotein S-100B released into the circulation is
      suggested to be a reliable marker indicating brain damage. The objective was to
      evaluate the neuroprotein S-100B serum levels in young amateur soccer players
      early after controlled heading compared to early measurements after normal
      exercise as well as in other patients after minor TBI. MATERIAL AND METHODS:
      Sixty-one male amateur soccer players (median age 15.3 years) performed
      controlled heading aimed at the forehead for 55 minutes. Data were compared to 58
      male amateur soccer players (15.9 years) performing 61 minutes of normal exercise
      training without head contact and 81 young male patients early after TBI who
      underwent computed tomography (CCT) for detection of intracranial lesions. First
      venous blood samples were drawn before the training sessions, second and third
      samples 60 and 360 minutes after heading or 64 and 355 minutes after exercise,
      respectively, 65 and 366 minutes after TBI. RESULTS: Median S-100B serum levels
      of the heading group only slightly increased from 0.15 ng/ml to 0.18 ng/ml 60
      minutes after end of training. Within 360 minutes S-100B values decreased again
      to 0.15 ng/ml reaching the initial values. S-100B serum values of the exercise
      group showed a similar transient increase exhibiting significant lower levels
      before exercise (0.10 ng/ml) as well as 64 minutes (0.11 ng/ml) and 355 minutes
      after exercise (0.09 ng/ml) compared to the heading group. According to age
      stratification in the heading group, starting median S-100B levels were
      significantly higher in subjects with 12-13 years (0.22 ng/ml) and 14-15 years
      (0.17 ng/ml) compared to those with 16-17 years of age (0.06 ng/ml). None of the
      subcollectives did reach median S-100B levels of the CCT+ group (n = 20) at
      admission (0.62 ng/ml) or 366 minutes later (0.32 ng/ml), which were
      significantly elevated compared to those of the CCT group (n = 61) at admission
      (0.10 ng/ml) or 370 minutes later (0.08 ng/ml). CONCLUSIONS: Controlled
      repetitive heading in young amateur soccer players leads to a transient increase
      between 60 to 360 min after training, but does not appear to evoke a longer
      lasting S-100B release into serum indicating cellular brain damage. After heading
      S-100B levels are significantly elevated compared to normal exercise. Although
      soccer players with 12-13 years and 14-15 years revealed significantly higher S
      100B values than with 16-17 years of age, the transient increase is independent
      of the age-related starting values. However, since brain damage due to abrupt
      heading a ball of high speed or accidental trauma during regular soccer games
      cannot be excluded, S-100B measurements in soccer players are initiated during
      video-controlled soccer games.

PMID- 14594654
TI  - Measurements of respiratory capacity in patients with neuromuscular diseases.
AB  - Weakening of the respiratory muscles in patients with neuromuscular diseases
      (NMDs) threatens them with respiratory failure. The respiratory capacity of these
      patients is estimated by pulmonary functional tests. One of the most frequently
      used tests is the measurement of vital capacity (VC) and determination of the
      percentage share of the VC reference value (%VC). Different body parameters such
      as body height and body weight are used for determining the %VC. It is difficult
      to measure these parameters in wheelchair-bound NMD patients, especially those in
      more advanced stages of disease. Another reason for questioning the objectivity
      of spirometric testing in NMD patients is that many of them manifest severely
      weakened facial muscles and consequently have trouble with blowing. This article
      describes alternative testing of respiratory capacity and calculation
      (mathematical model) of predicted pulmonary functional values that is not based
      on the body height but on other more objectively measured anthropometrical
      parameters.

PMID- 14594655
TI  - Temporal analysis of goblet cells and mucin gene expression in murine models of
      allergic asthma.
AB  - In murine models of allergic asthma, mice repeatedly exposed to allergens or
      interleukin (IL)13 have numerous goblet cells in their airway epithelium, in
      contrast to healthy naive mice. This study evaluated whether a single airway
      exposure of ovalbumin or IL13 would produce goblet cell metaplasia. Following
      ovalbumin challenge, airway goblet cells were present by 1 day, increased further
      by day 2 and day 3, and decreased by day 8. Following IL13 exposure, some goblet
      cells were detected at 6 hours and increased by 18 and 48 hours. Goblet
      transition cells, which are morphologically but not histologically similar to
      goblet cells, were observed at 6 and 18 hours following IL13 exposure and day 1
      following ovalbumin challenge. Increased Muc5ac and Muc2 mRNA expression occurred
      following ovalbumin or IL13, but not saline, exposure. Mucin transcripts were
      localized to goblet cells in the surface airway epithelium. Muc5ac protein was
      expressed in some goblet transition and goblet cells. Overall, these data
      demonstrated that a single airway exposure to ovalbumin or IL13 is sufficient to
      generate goblet cell metaplasia and thus increase mucin gene expression in two
      strains of mice.

PMID- 14594656
TI  - Air exposure causes oxidative stress in cultured bovine tracheal epithelial cells
      and produces a change in cellular glutathione systems.
AB  - An air-liquid interface culture system accelerates cell differentiation and
      growth in airway epithelial cells. In this study, the authors investigated
      whether glutathione (GSH) affects cell growth in an air-liquid interface culture.
      Various components of the cellular GSH system were measured and the number of
      cells was counted after conversion from an immersed feeding to an air-liquid
      interface. The effect of medium supplementation with cystine, a precursor of GSH,
      on cell growth was also examined. After conversion to an air-liquid interface,
      the cellular GSH level increased by 4 to 5-fold. The increase in GSH preceded the
      rise in cell number. The glutathione disulfide (GSSG)/total GSH ratio (an
      indicator of oxidative stress) increased initially and reached a plateau (time 0:
      0.379%+/-0.054%; day 2: 0.824%+/-0.063%; day 6: 0.806%+/-0.093%). The level of
      glutathione reductase activity in the cells increased in a time-dependent manner,
      whereas the glutathione peroxidase activity level declined. When the amount of
      cystine in the medium was varied after conversion, the cellular GSH level was
      closely correlated with the rate of cell growth. In conclusion, air exposure
      causes oxidative stress in cultured cells and produces a change in the cellular
      glutathione system, resulting in the promotion of cell growth.

PMID- 14594657
TI  - Hypoxia and reoxygenation increase H2O2 production in rats.
AB  - To test the effect of transition from sustained hypoxia to normoxia on production
      of reactive oxygen species (ROS) in lungs, the authors measured hydrogen peroxide
      (H(2)O(2)) output in the expired air of rats breathing hypoxic, normoxic, and
      hyperoxic gas mixtures at the end of exposure to 72 hours of hypoxia. Twenty-one
      male Wistar rats (200 to 280 g) were randomly assigned to 1 of 3 groups. First
      two groups (experimental) were kept for 3 days in normobaric hypoxic chamber
      (F(1)O(2) 0.1), rats of the third group (controls) breathed air. The rats were
      then anesthetized, intubated, placed in the plethysmograph, and their ventilation
      measured. Two periods of exhaled breath condensate (EBC) collection, each lasting
      1 hour, were then performed to assay H(2)O(2) output. The controls breathed
      during both samplings air, the first experimental group breathed during first
      sampling period hypoxic mixture (F(1)O(2) 0.1; SH-H measurement) and then, during
      second period, air (SH-H-A measurement), the second experimental group breathed
      first air (SH-A measurement) and then hyperoxic mixture (F(1)O(2) 1.0; SH-A-O(2)
      measurement). Concentration of H(2)O(2) in the EBC was assayed by
      chemiluminescence. H(2)O(2) production in the control group was low and similar
      in both measurements (20+/-10 and 13+/-5 pmol/h, mean+/-SEM). Exposure to 72
      hours of hypoxia increased the H(2)O(2) production to 105+/-18 pmol/h (SH-H).
      Transition from hypoxia to normoxia resulted in an increase in the H(2)O(2)
      production (SH-A 421+/-24 pmol/h, and SH-H-A 366+/-19 pmol/h). Following
      transition from air breathing to hyperoxia did not affect the H(2)O(2) production
      (SH-A-O(2) 373+/-25 pmol/h). The results showed that sustained hypoxia and
      transition from sustained hypoxia to normoxia increased H(2)O(2) formation in the
      lungs.

PMID- 14594658
TI  - Pulmonary toxicity studies in rats with triethoxyoctylsilane (OTES)-coated,
      pigment-grade titanium dioxide particles: bridging studies to predict inhalation
      hazard.
AB  - The aim of this study was to assess and compare the acute lung toxicities of
      intratracheally instilled hydrophobic relative to hydrophilic surface-coated
      titanium dioxide (TiO(2)) particles using a pulmonary bridging methodology. In
      addition, the results of these instillation studies were bridged with data
      previously generated from inhalation studies with hydrophilic, pigment-grade
      (base) TiO(2) particles, using the base, pigment-grade TiO(2) particles as the
      inhalation/instillation bridge material. To conduct toxicity comparisons, the
      surface coatings of base pigment-grade TiO(2) particles were made hydrophobic by
      application of triethoxyoctylsilane (OTES), a commercial product used in plastics
      applications. For the bioassay experimental design, rats were intratracheally
      instilled with 2 or 10 mg/kg of the following TiO(2) particle-types: (1) base
      (hydrophilic) TiO(2) particles; (2) TiO(2) with OTES surface coating; (3) base
      TiO(2) with Tween 80; or (4) OTES TiO(2) with Tween 80. Saline instilled rats
      served as controls. Following exposures, the lungs of sham- and TiO(2)-exposed
      rats were assessed both using bronchoalveolar lavage (BAL) biomarkers and by
      histopathology of lung tissue at 24 hours, 1 week, 1 month, and 3 months post
      exposure. The results demonstrated that only the base, high-dose (10 mg/kg)
      pigment-grade TiO(2) particles and those with particle-types containing Tween 80
      produced a transient pulmonary inflammatory response, and this was reversible
      within 1 week postexposure. The authors conclude that the OTES hydrophobic
      coating on the pigment-grade TiO(2) particle does not cause significant pulmonary
      toxicity.

PMID- 14594659
TI  - Inhalation of diesel exhaust for three months affects major cytokine expression
      and induces bronchus-associated lymphoid tissue formation in murine lungs.
AB  - The authors investigated the effects of exposure to diesel exhaust (DE) on murine
      lung tissues in vivo. BALB/c and C57BL/6 mice were exposed to DE with low (100
      microg/m(3)) and high (3 mg/m(3)) DE particle levels for 3 months. The authors
      then examined morphological changes and the expression of mRNAs for various
      cytokines (tumor necrosis factor [TNF]-alpha, interleukin [IL]-1beta, IL-4, IL-6,
      IL-10, IL-12p40, and interferon [IFN]-gamma) and inducible nitric oxide synthase
      (iNOS) in the lungs, as well as TNF-alpha, IL-1beta, IL-10, IL-12p40, and Mac-1
      mRNA expression in alveolar macrophages (AMs). TNF-alpha, IL-12p40, IL-4, and IL
      10 mRNA expression were mildly increased, whereas IL-1beta mRNA and iNOS
      expression were slightly decreased, in the low- and high-level exposure groups.
      Flow cytometry of bronchoalveolar lavage fluid revealed a significant increase in
      Mac-1-positive cells in the high-level exposure group. On histological
      examination, bronchus-associated lymphoid tissue (BALT), containing B and T
      lymphocytes, had developed only in the high-level exposure group. Chronic
      inhalation of DE influences cytokine expression in the murine lung, and induces
      phagocytosis and BALT development. These findings suggest that DE may provoke
      immunological responses by acting as a foreign body in the lung, and that even
      low-level exposure may induce allergic reactions.

PMID- 14594660
TI  - In vitro/in vivo evaluation of the efficiency of teicoplanin-loaded biodegradable
      microparticles formulated for implantation to infected bone defects.
AB  - Chronic osteomyelitis is still the cause of many problems in orthopaedics in
      terms of therapy and infection persistence. Four-to-six week systemic antibiotic
      therapy is required along with bone and soft tissue debridement in the therapy of
      chronic osteomyelitis. Prolonged-release local antibiotic therapy has been taken
      into consideration due to the side effects encountered in long-term high dose
      antibiotic use and the duration of hospitalization of the patients. Although
      local antibiotic therapy has been achieved by bone cement, a second surgical
      operation is needed for the removal of the system. On the other hand, heat
      generation during cement curing limits the use of heat-sensitive active
      ingredients. The most frequent osteomyelitis inducing micro-organism is gram (+)
      Staphylococcus aureus. In this study, teicoplanin, a glycopeptide antibiotic,
      active on gram (+) bacteria, was incorporated in a synthetic polymer in order to
      prepare a microsphere formulation for implantation to bone defects. Particle
      size, surface characteristics, loading capacity and in vitro release
      characteristics of the microspheres were determined as well as stability
      assessment of teicoplanin under accelerated conditions. In vivo studies were
      performed on rabbits and the microparticles were implanted intra-articularly to
      the lateral condylus of the femur. Antibiotic presence was detected by a
      microbiological assay from synovial fluid sample aspirated throughout 5 weeks. In
      the light of these evaluations, microspheres prepared from PLGA (75:25) (Mw
      136,000) polymer were determined to be effective, and promising for obtaining
      prolonged local antibiotic release.

PMID- 14594661
TI  - In situ poly(urea-formaldehyde) microencapsulation of dicyclopentadiene.
AB  - Microencapsulated healing agents that possess adequate strength, long shelf-life
      and excellent bonding to the host material are required for self-healing
      materials. Urea-formaldehyde microcapsules containing dicyclopentadiene were
      prepared by in situ polymerization in an oil-in-water emulsion that meet these
      requirements for self-healing epoxy. Microcapsules of 10-1000 microm in diameter
      were produced by appropriate selection of agitation rate in the range of 200-2000
      rpm. A linear relation exists between log(mean diameter) and log(agitation rate).
      Surface morphology and shell wall thickness were investigated by optical and
      electron microscopy. Microcapsules are composed of a smooth 160-220 nm inner
      membrane and a rough, porous outer surface of agglomerated urea-formaldehyde
      nanoparticles. Surface morphology is influenced by pH of the reacting emulsion
      and interfacial surface area at the core-water interface. High yields (80-90%) of
      a free flowing powder of spherical microcapsules were produced with a fill
      content of 83-92 wt% as determined by CHN analysis.

PMID- 14594662
TI  - Preparation and in vitro release behaviour of 5-fluorouracil-loaded microspheres
      based on poly (L-lactide) and its carbonate copolymers.
AB  - A modified oil-in-oil (o/o) emulsion solvent evaporation technique was adopted to
      prepare 5-fluorouracil (5-Fu)-loaded poly (L-lactide) (PLLA) or its carbonate
      copolymer microspheres. The disperse phase was a drug:polymer solution using a
      solvent mixture of N,N-dimethylformamide (DMF) and acetonitrile and the
      continuous phase was liquid paraffin containing 1-10% (w/v) Span 80(R). The
      effects of preparative parameters, such as the composition of the inner oil
      phase, drug:polymer ratio, polymer concentration and agitation rate, on 5-Fu
      entrapment efficiency and microsphere characteristics were investigated. By
      introducing 25% (v/v) DMF into the inner oil phase, microspheres with high drug
      entrapment efficiency and an ameliorated burst effect were achieved. Using this
      modified method, microspheres with various particle sizes could be produced with
      a high 5-Fu entrapment efficiency (about 80%). In vitro drug release tests showed
      a burst release of 5-Fu from PLLA microspheres, followed by a sustained release
      over 50 days. In the case of poly (L-lactide-co-1,3-trimethylene carbonate)
      (PLTMC) and poly (L-lactide-co-2,2-dimethyl-1,3-trimethylene carbonate) (PLDTMC),
      the drug release could be continued for over 60 days.

PMID- 14594663
TI  - Injectable nanospheres from a novel multiblock copolymer: cytocompatibility,
      degradation and in vitro release studies.
AB  - The aim was to develop and characterize nanospheres made from a newly synthesized
      poly (D,L-lactide-co-ethyleneglycol) (-PLA-PEG-PLA-)n multiblock copolymer.
      Nanospheres were prepared under optimized conditions of modified emulsion-solvent
      evaporation technique in a continuous flow process using rhodamine B as a drug
      model. They were characterized for size distribution, zeta (zeta) potential,
      porosity and morphology. Drug loading and yield were also determined. In vitro
      degradation studies of the copolymer were conducted in phosphate buffer (pH 7.4)
      at 37 degrees C. The cytotoxic properties of the polymer and vector were analysed
      by dimethylthiazoldiphenyltetrazolium bromide (MTT) and lactate dehydrogenase
      (LDH) assays on the B16 mouse cell line. Release of rhodamine B from the
      nanospheres was assayed in vitro using a dialysis bag in isotonic phosphate
      buffer (pH 7.4) at 37 degrees C. Spherical and non-porous nanospheres with mean
      size less than 800 nm could be prepared. The (zeta) potential was neutral. The
      average yield was approximately 70% with 7% rhodamine loading. A total of 50% of
      the multiblock underwent initial degradation after 4 weeks, while degradation was
      complete after 16 weeks. Cellular proliferation was not inhibited as no
      cytotoxicity was observed with the copolymers and nanospheres. Rhodamine B was
      released in a stepwise pattern. The initial burst was 20%, and release was
      prolonged thereafter for 29 days. Thus, injectable nanospheres with prolonged
      rhodamine B release have been designed and characterized as a potential drug
      delivery system.

PMID- 14594664
TI  - Encapsulation of recombinant hepatitis B surface antigen in oligosaccharide ester
      derivatives by spray drying.

PMID- 14594666
TI  - Oxprenolol-loaded bioadhesive microspheres: preparation and in vitro/in vivo
      characterization.
AB  - Biologically adhesive delivery systems offer important advantages over
      conventional drug-delivery systems. In this paper, microspheres intended as a
      sustained release carrier for oral or nasal administration have been prepared by
      associating a known bioadhesive polymer, poly(acrylic acid), in gelatin
      microspheres. A model drug oxprenolol hydrochloride was chosen. It was found that
      some of the formulation variables can influence the characteristics of the beads
      in a controlled manner. The internal structure of the microspheres studied by X
      ray diffraction, thermal analysis and optical microscopy showed the absence of
      drug crystals in microspheres and a lowering in the glass transition temperature.
      The dynamic swelling of the beads obeyed the square root of time and a shift from
      the diffusional to the relaxational process dependent on the content of
      poly(acrylic acid) in gelatin microspheres was observed. As expected, drug
      release from gelatin/poly(acrylic acid) microspheres was influenced by the
      poly(acrylic acid) content in beads, by the particle size of microspheres and by
      the pH of the medium. The mechanism of release was analysed by applying the
      empirical exponential equation and by calculation of the approximate contribution
      of the diffusional and relaxational mechanisms to the anomalous release process
      by fitting the data to the coupled Fickian/Case II equation. In vitro and in vivo
      experiments in rats showed good adhesive characteristics of the
      gelatin/poly(acrylic acid) microspheres, which were greater if the poly(acrylic
      acid) content was greater. A significant retardation in gastric and intestinal
      emptying time of the beads was observed. This was also suggested by the
      bioavailability of the model drug after intragastric and intranasal
      administration of the microspheres. The pharmacokinetic parameters after
      microsphere administration were more appropriate to a slow release drug-delivery
      system. The work suggests the potential of this pharmaceutical delivery system as
      an alternative controlled-release dosage form, either for oral or nasal
      administration.

PMID- 14594665
TI  - Usefulness of microspheres composed of gelatin with various cross-linking
      density.
AB  - The release rate of insulin, as a model peptide, from gelatin microspheres (GM)
      prepared with gelatin having various cross-linking densities in vitro was
      examined. The release of insulin from GM showed the burst effect, followed by a
      slow release phase regardless of the cross-linking density of gelatin. The total
      amount of insulin released in 2 weeks decreased with increasing cross-linking
      density of gelatin. The release rate of insulin within 6 h was well correlated
      with the cross-linking density of gelatin. The remaining amounts of both insulin
      and GM after injection of insulin incorporated in GM to mice femoral muscle
      tissue were also examined in vivo. Both insulin and GM rapidly disappeared from
      the injection site within 1 day, and thereafter slowly disappeared over 14 days.
      The time courses of the remaining amounts were fairly similar to each other.
      Furthermore, the remaining amount of insulin 1 day after administration was well
      correlated with the cross-linking density of gelatin. These data suggest that
      insulin was released from GM with the degradation of GM in mice muscular tissue
      and that the release rate of insulin can be controlled by modifying the cross
      linking density of gelatin. In conclusion, the control of the release rate of
      insulin from GM can be achieved under both in vitro and in vivo conditions by
      gelatin through the alteration of cross-linking conditions.

PMID- 14594667
TI  - Chitosan microparticle preparation for controlled drug release by response
      surface methodology.
AB  - The objectives were to investigate the effects of formulation variables on the
      release of drug and to optimize the formulation of chitosan microparticles loaded
      with drug for controlled release using response surface methodology. Chitosan
      microparticles were prepared by dropping a chitosan solution into sodium
      tripolyphosphate (TPP) through ionic cross-linking. The release behaviour of
      felodipine as a model drug was affected by preparation variables. A central
      composite design was used to evaluate and optimize the effect of preparation
      variables, chitosan concentration (X1), the pH of the TPP solution (X2) and cross
      linking time (X3) on the cumulative per cent drug release (Y) in 24 h. Chitosan
      concentration and cross-linking time affected negatively the release of
      felodipine, while the pH of the TPP did so positively and was the highest
      influential factor. The optimum rate of drug release, 100% in 24 h, was achieved
      at 1.8% chitosan concentration, a pH 8.7 for the TPP solution and 9.7 min cross
      linking time.

PMID- 14594668
TI  - Poly (D,L-lactide-co-glycolide) microspheres for long-term intravitreal delivery
      of aciclovir: influence of fatty and non-fatty additives.
AB  - Aciclovir (acicloguanosine) has been demonstrated to be effective in the
      treatment of intraocular pathologies such as herpes simplex virus retinitis and
      acute retinal necrosis. Although intravitreal injections have been used with
      fewer side-effects than intravenous administration, the risk of complications
      increases with the frequency of intravitreous injections. For this reason, a
      biodegradable drug-delivery system, such as microspheres, able to promote
      prolonged release of the drug, offers a good alternative to multiple intraocular
      administrations. In this work, aciclovir-containing poly (D,L-lactide-co
      glycolide) microspheres were prepared by the solvent evaporation method. Seven
      additives were incorporated in the microspheres to modulate the in vitro release
      rate of the drug: four non-fatty substances (polyethylene glycol 300,
      polyethylene glycol 1500, hydroxypropyl methylcellulose and gelatin) and three
      fatty substances (isopropyl myristate, vitamin E and Labrafil M 1944 CS).
      Morphology of microspheres was evaluated by scanning electron microscopy.
      Granulometric analysis showed that particle size distribution was significantly
      influenced by the incorporation of additives. Loading efficiency decreased when
      fatty substances were added, whereas non-fatty additives promoted higher
      incorporation of the drug. Infrared and differential scanning calorimetry
      analyses indicated that microspheres prepared by the solvent evaporation process
      were not influenced by the type of additive used. In all cases, the initial burst
      resulted less than 5%. Additive-free microspheres showed a slow release within
      the first days, but when additives were incorporated, in general, the release
      rates of the drug were increased. Best release results were obtained for gelatin
      containing microspheres. The release of aciclovir from these microspheres was
      adjusted to a zero-order kinetic from 1 to 49 days with a release constant of
      1.13 microg/day/mg microspheres. A dose of 0.74 mg microspheres would be
      therapeutic for the herpes simplex and Epstein-Barr viruses (MIC 0.1 microg/ml)
      and 7.4 mg for varicella zoster virus (MIC 1 microg/ml) treatment in an animal
      model.

PMID- 14594672
TI  - Residues of DDT and HCH pesticides in rice samples from different geographical
      regions of India: a multicentre study.
AB  - As part of a multicentre study conducted by the Indian Council of Medical
      Research, 2000 samples of rice were collected from rural and urban areas of 13
      states representing different geographical regions of India. The samples were
      analyzed for residues of DDT [2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane] and
      different isomers of HCH [1,2,3,4,5,6-hexachlorocyclohexane, a mixture of
      isomers] by gas-chromatography. Residues of DDT and HCH, respectively, were
      detected in about 58 and 73% of the samples analysed. Medians of both DDT and HCH
      in rice samples were around 0.01 mg kg (-1). Concentrations of alpha-, beta-,
      gamma- and delta-HCH exceeded a maximum residue limit of 0.05 mg kg (-1) for each
      isomer in rice fixed by the Ministry of Health and Family Welfare of the Indian
      Government in 4.3, 2.6, 1.7 and 1.2% of the samples, respectively. There is no
      statutory limit fixed in India for DDT residues in cereals. Its maximum residue
      limit of 0.1 mg kg (-1) in cereals recommended by Codex was exceeded by about 2%
      of the samples examined. Estimated intake of DDT and isomers of HCH through
      consumption of rice contaminated at their median and 90th percentiles constituted
      a small proportion of their acceptable daily intakes.

PMID- 14594673
TI  - Analytical methods for the determination of acrylamide in food products: a
      review.
AB  - In early 2002, the Swedish National Food Administration reported high acrylamide
      levels in heat-treated carbohydrate-rich foods. Consequently, intensive activity
      began examining the many different types of food, and thousands of analyses have
      been undertaken world wide. Measurement data have been published in many
      different types of media. Within this flood of publications, there are only a
      limited number of articles concerned with the technical aspects of the
      measurements. This review focuses on the state-of-the-art in the analysis of
      acrylamide in foodstuffs. It covers information on methods from peer-reviewed
      articles and other sources (e.g. a survey carried out among official and private
      laboratories of the Member States of the European Union). Alternative methods are
      presented and discussed alongside the more common measurement techniques for
      acrylamide in foodstuffs. Special attention is given to sample preparation. The
      greatest differences between the analytical methods was for acrylamide extraction
      and clean-up. The influence of different extraction techniques or extraction
      solvents/solvent mixtures on the measurement results has not yet been fully
      investigated. There is also a lack of understanding about the sample clean-up.
      Since both might have a large impact on the results of the analysis, this review
      should also be considered as a basis for further investigations.

PMID- 14594674
TI  - Determination of 1,3-dichloropropanol in soy and related sauces by using gas
      chromatography/mass spectrometry.
AB  - A gas chromatography/mass spectrometry method for 3-MCPD in foods and food
      ingredients was modified for the determination of 1,3-DCP in soy and related
      sauces. The method was validated by using a blank soy sauce. The detection limit,
      quantitation limit and recoveries were determined, and identities were confirmed
      by mass spectrometry on the basis of analyses of test portions spiked with 1,3
      DCP at 10, 25, 50 and 100 ng g(-1). The spiked test portions were quantitated by
      using an internal standard calibration curve. For the spiked test portions, the
      mean internal standard-corrected recovery for 1,3-DCP was 100% with a relative
      standard deviation of 1.32%. The limits of detection and quantitation were
      determined as 0.055 and 0.185 ng g(-1), respectively. The method also was
      compared with a headspace GC/MS method recently developed by the UK's Central
      Science Laboratory. Results from the method comparison showed that the recoveries
      for the spiked test portions, as well as the amounts of 1,3-DCP found in the
      retail products, were comparable.

PMID- 14594675
TI  - Survey of chloropropanols in soy sauces and related products.
AB  - A survey of soy sauces and related products available in the USA was conducted to
      determine the levels of 3-monochloropropane-1,2-diol (3-MCPD) and 1,3-dichloro-2
      propanol (1,3-DCP) in these products. Fifty-five retail samples were purchased
      and analysed for 3-MCPD. 3-MCPD determinations were made according to a gas
      chromatography/mass spectrometry method validated by a collaborative trial.
      Eighty-five per cent of the samples analysed contained greater than the detection
      limit of 0.005 ppm (microg g(-1)) for 3-MCPD. Thirty-three per cent contained
      greater than 1 ppm; the highest level was 876 ppm 3-MCPD. Thirty-nine of the
      samples analysed for 3-MCPD also were analysed for 1,3-DCP by using a modified
      method developed and validated in-house. Fifty-six per cent of the samples
      analysed for 1,3-DCP contained greater than the detection limit of 0.055 ppb (ng
      g(-1)) for 1,3-DCP; the highest level was 9.8 ppm 1,3-DCP. Products manufactured
      in Asia contained the highest chloropropanol levels.

PMID- 14594676
TI  - Survey of chloropropanols in soy sauces and related products purchased in the UK
      in 2000 and 2002.
AB  - The results of surveys to investigate the levels of 3-monochloropropane-1,2-diol
      (3-MCPD) and 1,3-dichloropropanol (1,3-DCP) in UK retail samples of soy sauces
      and similar products are reported. The products, sampled in 2000 and 2002, were
      analysed for 3-MCPD using an established solvent extraction technique with a
      reporting limit of 0.01 mg kg(-1), which also detected 2-monochloropropane-1,2
      diol (2-MCPD), and for 1,3-DCP by an automated headspace method with a reporting
      limit of 0.005 mg kg(-1), which also detected 2,3-dichloropropanol (2,3-DCP). In
      the 2000 survey, 3-MCPD was quantified in 32 of 100 samples. After normalization
      to 40% dry matter, it was quantified at or above 0.02 mg kg(-1) in 25 of the
      samples and in excess of 1 mg kg(-1) in 16 samples, the highest containing 82.8
      mg kg(-1). 2-MCPD was found in 26 samples, at up to 17.6 mg kg(-1) after
      normalization to 40% dry matter. The presence of 1,3-DCP was detected in 17 of
      the samples, at levels between 0.006 and 0.345 mg kg(-1). 1,3-DCP was only
      detected where 3-MCPD was present, but the levels of 1,3-DCP and 3-MCPD were not
      correlated. 2,3-DCP was detected in 11 samples at levels ranging from 0.006 to
      0.043 mg kg(-1). In the 2002 survey, 3-MCPD was quantified (> 0.01 mg kg(-1)) in
      only eight of 99 samples and 2-MCPD in three samples. After normalization to 40%
      dry matter, 3-MCPD was present at or above 0.02 mg kg(-1) in seven of these, the
      maximum level being 35.9 mg kg(-1). 1,3-DCP was detected in this sample alone, at
      0.017 mg kg(-1).

PMID- 14594677
TI  - Determination of total arsenic levels by hydride generation atomic absorption
      spectrometry in foods from south-east Spain: estimation of daily dietary intake.
AB  - The total concentration of arsenic in different foods from south-east Spain was
      determined by hydride generation atomic absorption spectrometry. Mineralization
      was carried out with an HNO(3)-HClO(4) mixture in a thermostated sand bath.
      Arsenic determination was performed by the standard addition method. Analyses of
      NIST and CBR-CEC reference materials demonstrated the reliability and accuracy of
      the technique. The highest arsenic levels were found in seafood, cereals, meat
      and meat by-products. In meat and meat by-products, the total arsenic measured in
      meat was significantly higher than that in sausages (p<0.05). In cereals, arsenic
      concentrations in corn and white rice samples were significantly higher (p<0.01)
      than those measured in wheat by-products. Mean arsenic concentrations in cheese
      were statistically lower than those in other dairy products (p<0.01). New data
      have been provided on the total arsenic content of a variety of foods in Spain,
      which is important for making exposure estimates. The estimated daily intake of
      total arsenic in the Spanish diet was 221 microg As day(-1).

PMID- 14594678
TI  - Antimutagenic activity of phenolic compounds, oligosaccharides and quinolizidinic
      alkaloids from Lupinus campestris seeds.
AB  - There are some foods that contain mutagenic or carcinogenic agents, some of which
      occur naturally and others that may be formed during preparation or cooking.
      Several foods such as legumes, also contain natural antimutagens and/or
      anticarcinogens. Lupine is one such legume that contains high amounts of protein
      (40%) and oils (14%). About 90 species of lupine have been reported throughout
      Mexico. However, the use of this crop as a source of food has been limited by the
      presence of antinutritional agents such as phenolic compounds (PC), carbohydrates
      (CH) and quinolizidinic alkaloids (Qas). It has also been suggested that
      consuming these compounds can affect human health and may even reduce the risk of
      disease. The objective of this work was to determine the effect of PC, CH and
      Qas, isolated and quantified from Lupinus campestris on the mutagenicity of 1
      nitropyrene (1-NP) as a model mutagen and we used the Salmonella typhimurium
      tester strain YG1024 by the Kado microsuspension method. The results indicate
      that L. campestris seeds have 11 mg (+)catechin equivalent g(-1) seed coat; 120.3
      mg g(-1) seeds and 2.13 mg g(-1) seeds of PC, CH and Qas, respectively. 1-NP
      mutagenicity was inhibited by 86% for PC, 76% for CH and 75% for Qas at
      concentrations of 200, 512 and 13.6 microg/tube, respectively.

PMID- 14594679
TI  - Alternative fatty food simulants and diffusion kinetics of nylon 12 food
      packaging.
AB  - The migration of laurolactam and cyclic di- and trimer of nylon 12 was assessed
      using three different films and five food simulants (olive oil, isooctane, 95%
      ethanol, 50% ethanol, water). Substitute test conditions for migration into olive
      oil according to European Union Directive EC/97/48 were applied using 95% ethanol
      and isooctane. Results showed that 95% ethanol overestimated while isooctane
      underestimated the respective migration into olive oil. Water was the best olive
      oil substitute, as migration of laurolactam into water and olive oil using the
      same temperature gave similar results. Additionally, diffusion kinetics of
      laurolactam were investigated by migration kinetic studies using isooctane and
      olive oil. Diffusion coefficients determined with isooctane were significantly
      higher than those found using olive oil. It was proved that isooctane had an
      interaction and olive oil was inert to the polymer. The diffusion conductance
      parameter, A(p), for nylon 12 determined using olive oil ranged from 0.3 to 0.6.

PMID- 14594680
TI  - Mechanism of migration from agglomerated cork stoppers. Part 2: Safety assessment
      criteria of agglomerated cork stoppers for champagne wine cork producers, for
      users and for control laboratories.
AB  - Producers of cork for champagne and wine have to be certain the corks meet the
      requirements of the European Union Framework Directive, and comply with the
      evaluations of chemicals carried out in the European Union. To identify chemicals
      in cork with the potential to migrate, the different synthetic products on the
      market were classified based on their technical role and of the chemistry
      involved. The potential migrants in each class (adhesive for cork bodies,
      adhesive for cork disks, lubricants and surface treatments) were analysed
      spectroscopically and chromatographically. A general approach was proposed for
      the evaluation of each commercial chemical: the detailed composition was supplied
      and verified mainly by infrared spectroscopy, proton nuclear magnetic resonance
      spectroscopy ((1)H-NMR) and GC-MS. A procedure to determine primary aromatic
      amines, specifically for cork migrates, based on GC-MS was developed. These
      techniques focussed on migrants below 1000 g mol(-1), as higher molecular weight
      chemicals are not likely to pose a problem for public health. The products were
      also tested after polymerization. The analytical scheme included an analytical
      check of synthetic product formulation and identification of potential migrants,
      solvent extraction and analysis of cork extracts.

PMID- 14594681
TI  - Contaminants and levels of occurrence in washed and shredded poly(ethylene
      terephthalate) from curbside collection. II: Validation of extraction procedures,
      particle size sampling and crystallinity.
AB  - Part I of this study showed that washed and dried, shredded poly(ethylene
      terephthalate) (PET) (flake) obtained from curbside collection when Soxhlet
      extracted contained 26 semivolatile contaminants below the US FDA threshold of
      215 ppb and six above this level. This paper reports the validation of the
      Soxhlet extraction technique by comparison with total dissolution with
      trifluoroacetic acid (TFA). The work was carried out for two of the three
      particle size ranges obtained by grinding the PET flake (300-425 and 425-700
      microm) and for the unground flake. Further validation was undertaken by
      comparison of contaminant levels determined by total dissolution with TFA and
      sonication with dichloromethane (DCM) using flake ground to the 0-300 microm size
      range. The levels of contaminants increased with decreasing particle size range,
      but X-ray diffraction measurements of degrees of crystallinity were similar for
      each PET particle size range, thus showing that the differences in contaminant
      levels were not due to variable percentages of the amorphous material from the
      tops and bottoms of shredded bottles, relative to the amounts of crystalline PET
      from the mid-sections of the bottles. Hence, it was postulated that the
      variations in contaminant levels were due to selective grinding of the more
      highly contaminated surfaces, whilst the larger particles incorporated the less
      contaminated interior material. The grinding was also strongly selective with
      respect to the amorphous flake. Analysis of the segregated amorphous and
      crystalline flake phases indicated that many contaminants were similarly absorbed
      into both phases, whilst some were preferred by the amorphous PET and others were
      preferred by the crystalline PET.

PMID- 14594682
TI  - Migration of volatile degradation products into ozonated water from plastic
      packaging materials.
AB  - Migration of volatile degradation products from poly(ethylene terephthalate)
      (PET) and high-density polyethylene (HDPE) bottles, polypropylene (PP) caps and
      ethyl vinyl acetate (EVA) liners into ozonated water was measured. Polymer strips
      were immersed in deionized and distilled water with ozone concentrations of 0.5,
      2.5 and/or 5 mg kg(-1) inside 35-ml vials, which were clamp-sealed and stored at
      40 degrees C for 10 days. A purge-and-trap unit was developed to extract volatile
      products from the ozonated water in vials. The extractables were trapped in an
      adsorbent tube and analysed using a GC-MS coupled with an automated thermal
      desorber (ATD). Mass spectra were interpreted by comparison with a NIST mass
      spectral library, and an internal standard method was used to quantify the
      extractables of interest. Several volatile compounds found in ozonated water that
      had been in contact with PP, EVA and HDPE polymers included butanal, pentanal,
      hexanal, heptanal, octanal, nonanal, 2,2-dimethyl propanal, 3-hexanone, 2
      hexanone and heptanone. These compounds could cause off-taste and off-odour with
      a low organoleptic threshold. In general, the concentrations of these volatile
      compounds increased with an increased exposure to ozone. The highest
      concentration found was 14.1 +/- 0.6 microg kg(-1) for hexanal with a 5 mg kg(-1)
      ozone treatment of PP caps. Even at a treatment level of 5 mg kg(-1) ozone, which
      is greater than 10 times the current regulatory limits for bottled water, the
      extractables migrating from those polymers were within the levels permitted by
      the FDA. For the PET sample, no significant peaks were observed before or after
      ozonation. These results imply that PP caps containing EVA liners may be major
      sources of off-odour and taste in ozonated bottled water.

PMID- 14594683
TI  - Prostate cancer--prevalence-based healthcare costs.
AB  - OBJECTIVE: To calculate the total costs of in- and outpatient healthcare for
      patients with prostate cancer based on an episode-of-care approach. The cost
      analysis includes costs incurred during the first year of diagnosis, a
      longitudinal 3-year analysis and the incremental cost of prostate cancer during
      the first year of diagnosis. MATERIAL AND METHODS: Patients registered with
      prostate cancer between 1998 and 2000, according to the data files of the
      Southern Swedish Regional Tumour Registry, were given encrypted identifiers that
      could also be used in the Patient Administrative System of the Region Skane
      County Council, making it possible to identify consumption of healthcare on an
      episode-of-care basis. Itemized costs for resources used by each individual
      patient were calculated from the complete accounting system of the County
      Council. RESULTS: Healthcare costs for prostate cancer during the first year
      varied between 45 000 and 51 000 SEK per patient. The second- and third-year
      costs were progressively lower, with an estimated total cost of 114 000 SEK over
      a period of 3 years. The age-standardized incremental cost of prostate cancer
      corresponded to 33 000 SEK during the first year, compared to the average cost
      per inhabitant. CONCLUSIONS: The episode-of-care approach, based on encrypted
      identifiers for the identification of the diagnoses of individual patients and
      their utilization of healthcare, gives a unique opportunity to estimate the
      healthcare costs of specific diseases. The incremental healthcare cost per
      patient with prostate cancer corresponded to 33 000 SEK during the first year.

PMID- 14594684
TI  - Radical prostatectomy--long-term oncological outcome from a community hospital.
AB  - OBJECTIVE: Radical prostatectomy has recently been shown to prolong cancer
      specific survival compared to watchful waiting in patients with localized
      prostate cancer. Most patients who seek medical advice for this disease are
      treated in hospitals in which the operation is performed relatively infrequently.
      The aim of this study is to report the oncological outcome at intermediate- to
      long-term follow-up after radical prostatectomy performed in a community
      hospital. MATERIAL AND METHODS: A total of 148 patients underwent radical
      prostatectomy at Ryhov County Hospital between 1985 and 1997. Patients without T3
      tumours, prostate-specific antigen (PSA) >10 ng/ml or poorly differentiated
      tumours were judged to be in a low-risk group, those with one risk factor to be
      in an intermediate group and those with two or more factors to be in a high-risk
      group. The projected biochemical disease free- and cancer-specific survival rates
      were compared between these risk groups. RESULTS: Median follow-up was 96 months
      for surviving patients. Patients in the low- and intermediate risk groups had
      equal 10-year PSA-free survival rates of 68.8%, while that in the high-risk group
      was only 19.3% (9-year data). Corresponding cancer-specific survival rates were
      93% and 84%, respectively. CONCLUSIONS: The oncological outcome seems comparable
      to that reported in the literature, even when the operation is performed in a low
      volume community-based setting.

PMID- 14594685
TI  - Laparoscopic pelvic lymph node dissection allows significantly more accurate
      staging in "high-risk" prostate cancer compared to MRI or CT.
AB  - OBJECTIVE: To compare the accuracy of lymph node staging using pelvic MRI or CT
      to that of laparoscopic pelvic lymph node dissection (LPLND) in prostate cancer
      patients prior to radical radiotherapy. MATERIAL AND METHODS: A total of 55
      consecutive patients at high risk of locally advanced disease [prostate-specific
      antigen (PSA) > 10 ng/ml, Gleason score 7 or worse on biopsy, normal (99m) Tc
      bone scan] underwent either a pelvic MRI (n = 42) or CT (n = 13) scan and
      subsequent LPLND. Preoperative staging was compared to the histology of the lymph
      node specimens obtained. RESULTS: A total of 20/55 (36.4%) patients had pelvic
      lymph node metastases confirmed by LPLND. MRI identified three patients (27.3%)
      with pelvic lymph node metastases and missed eight (72.7%) whilst CT identified
      none of nine patients with pelvic lymph node metastases. The groups with
      histologically-positive and -negative nodes had similar mean ages (63 vs 65
      years; p = 0.52), Gleason scores (6.8 vs 6.5; p = 0.41) and PSA levels (43.1 vs
      31.4 ng/ml; p = 0.56). CONCLUSION: The presence or absence of lymph node
      metastases has critical implications for the prognosis and treatment of prostate
      cancer. In this study both MRI and CT missed many cases of lymph node metastases
      in "high-risk" patients. While a positive scan seems likely to indicate nodal
      metastases, the low sensitivity in high-risk patients seems unacceptable if
      treatment decisions are to be based on accurate staging, and LPLND offers an
      alternative.

PMID- 14594686
TI  - The role of the pathologist in the evaluation of radical prostatectomy specimens.
AB  - OBJECTIVE: To compare the difference between the routinely reported pathology
      records and the results of re-evaluation of the same radical retropubic
      prostatectomy (RRP) specimens. MATERIAL AND METHODS: The RRP specimens of 114
      patients initially reported by a general pathologist for routine purposes were re
      examined and re-evaluated blindly with respect to the following parameters: organ
      confinement; capsular invasion; seminal vesicle invasion; lymph node metastasis;
      surgical margin positivity; Gleason grade and pathologic stage. Repeat and step
      sections were performed where necessary. Prostate mapping was done for each
      patient. RESULTS: A statistically significant discordance between the routine
      evaluation and the re-evaluation was observed with regard to capsular invasion,
      organ confinement, Gleason grade and pathologic stage. In addition to pathologic
      stage, Gleason grade and surgical margin positivity became significant prognostic
      factors after the re-evaluation. CONCLUSIONS: RRP specimens should be evaluated
      by an expert prostate pathologist by submitting whole prostate specimens and
      should include detailed prostate mapping.

PMID- 14594688
TI  - Diagnostic delay and prognosis in invasive bladder cancer.
AB  - OBJECTIVES: To study diagnostic delay in invasive bladder cancer in a population
      based material with long-term follow-up, and to evaluate whether delay in
      diagnosis affects the risk of bladder cancer death. MATERIAL AND METHODS: In a
      previous study, 177 patients with invasive bladder cancer (T1-T4) diagnosed in
      1988 were investigated with regard to diagnostic delay. A review of all available
      clinical records was performed. In the present study, causes of death for these
      patients were registered over a 12-year follow-up period, and the impact of
      diagnostic delay on bladder cancer death was studied by means of survival
      analysis. RESULTS: The median diagnostic delay in the material was 144 days. When
      the patients were stratified into groups with diagnostic delays of 0-3, 3-6, 6-12
      and >12 months, those with T1 tumours in the two groups with a diagnostic delay
      of <6 months showed a trend towards a decreased risk of bladder cancer death. In
      contrast, in patients with muscle-invasive disease, a significantly increased
      risk of bladder cancer death was noted for those with a diagnostic delay of <6
      months. CONCLUSION: A trend towards better prognosis was found for patients with
      T1 tumours with a shorter diagnostic delay. The poor prognosis of patients with
      muscle-invasive disease and a short diagnostic delay suggests aggressive
      behaviour of the tumour and may explain the worse prognosis in these patients.

PMID- 14594687
TI  - Introducing a new, simple scoring system to evaluate oncological and functional
      outcome after radical prostatectomy.
AB  - OBJECTIVE: To create a scoring system which takes into account oncological
      outcome and functional results (continence and erectile function) of patients
      after radical prostatectomy. MATERIAL AND METHODS: A total of 146 consecutive men
      underwent radical prostatectomy for localized prostate cancer and were evaluated
      1 year after surgery. Biochemical recurrence was defined as a single
      postoperative prostate-specific antigen (PSA) level of > 0.2 ng/ml. Continence,
      defined as not using a pad, and potency, defined as the ability to achieve and
      maintain an erection suitable for sexual intercourse, were evaluated by means of
      a prospective, self-administered questionnaire. Each patient received 4 points
      (if PSA was <0.2 ng/ml) or 0 points (if PSA was >0.2 ng/ml) for oncological
      outcome, 2 points (if continent) or 0 points (if incontinent) for urinary
      continence and 1 point (if potent) or 0 points (if impotent) for erectile
      function. The total score was calculated, with higher scores indicating a better
      outcome. The unique feature of this scoring system is that each individual score
      represents a particular clinical status regarding oncological and functional
      outcome. RESULTS: One year after surgery, 121 (82.8%) patients had PSA levels of
      <0.2 ng/ml, 103 (70.5%) were continent and 53 (36.3%) were potent. Patients with
      a total score of > or =4 points had good cancer control and could be further
      subdivided into those who were continent and potent (7 points; 22.6%), those who
      were continent but had erectile dysfunction (ED) (6 points; 34.2%), those who
      were incontinent and potent (5 points; 8.2%) and those who were incontinent and
      had ED (4 points; 17.8%). Similarly, patients with a score of <4 points had no
      cancer control and could be further subdivided into those who were continent and
      potent (3 points; 3.4%), those who were continent but had ED (2 points; 10.3%),
      those who were incontinent and potent (1 point; 2.1%) and those who were
      incontinent and had ED (0 points; 1.3%). CONCLUSIONS: This scoring system
      includes the three most important outcomes after radical prostatectomy, namely
      cancer control, continence and erectile function. It may allow us to better
      evaluate, communicate and compare the results of radical prostatectomy in a
      multinational, multicenter setting.

PMID- 14594689
TI  - Status of pretreatment evaluation, treatment and follow-up regimens for renal
      cell carcinoma in the Nordic countries.
AB  - OBJECTIVE: One prerequisite for performing multicentre studies is that the
      clinical handling of the patients must be uniform. We therefore evaluated
      possible differences in pretreatment evaluation, surgical treatment and follow-up
      regimes between the Nordic countries and between the different departments that
      performed nephrectomy due to renal cell carcinoma. MATERIAL AND METHODS: A
      questionnaire comprising 21 different questions was sent to all hospitals in the
      five Nordic countries performing nephrectomy. The questionnaires were returned by
      195/226 (86%) departments. RESULTS: In total, 24% of the departments performed
      fewer than five tumour nephrectomies per year. The main differences were as
      follows. I.v. pyelography was never used in Finland in clinics with urologists
      while preoperative CT scans were performed by most departments and in most
      countries. Cytology/biopsy examinations were never used in urological clinics in
      Finland and Iceland in contrast to 31% of urological clinics in Denmark. In
      Finland, 69% of the departments performed nephrectomy in patients with multiple
      distant metastases, compared to only 15% in the other Nordic countries. Follow-up
      after nephrectomy was done in 38% of Danish departments and in 96% of departments
      in the other Nordic countries. CONCLUSION: There were evident differences between
      the urological/surgical departments in the five Nordic countries, especially
      concerning radiological evaluation, treatment of patients with metastases and
      postoperative follow-up.

PMID- 14594690
TI  - Effects of extracorporeal shock-wave lithotripsy on intrarenal resistive index.
AB  - OBJECTIVE: This prospective study was performed to determine whether
      extracorporeal shock-wave lithotripsy (ESWL), widely used for treating renal and
      ureteral stones, affects the kidney interlobar artery resistive index (RI).
      MATERIAL AND METHODS: A total of 43 patients (30 with renal and 13 with ureteral
      stones) underwent color Doppler examination before and 30 min and 3 h after ESWL.
      Seventeen patients with renal and nine with ureteral stones underwent Doppler
      examination 2 weeks later. Measurements were made near the stones (nearby
      region), at least 2 cm from the stones (remote region) and in the contralateral
      kidney for renal stones, and in the ipsilateral and contralateral kidneys for
      ureteral stones. RESULTS: In patients with renal stones, the RI was increased 30
      min and 3 h after ESWL in the nearby and remote regions, and more markedly in the
      former. In the contralateral kidney, there was an increase in RI only at 3 h,
      which was less than that in the ipsilateral kidney. The RI at 2 weeks post-ESWL
      in the nearby region and contralateral kidney did not differ from the pre-ESWL
      values. ESWL performed for ureteral stones caused no increase in RI in the
      ipsilateral kidney. CONCLUSION: Patients with renal stones had a temporary
      increase in RI in the hours following ESWL in both the ipsilateral and
      contralateral kidneys, which was highest in the region near the stones and lowest
      in the contralateral kidney. Two weeks later, the RI in both areas had returned
      to pre-ESWL levels.

PMID- 14594691
TI  - Prognostic factors for extracorporeal shock-wave lithotripsy of ureteric stones-
      a multivariate analysis study.
AB  - OBJECTIVE: To define factors that have a significant impact on the stone-free
      rate after extracorporeal shock-wave lithotripsy (ESWL) of ureteric stones using
      multivariate analysis. MATERIAL AND METHODS: Between February 1992 and February
      2002, a total of 938 patients with ureteric stones were treated with in situ ESWL
      using the Dornier MFL 5000 lithotripter. The outcome of treatment was evaluated
      after 3 months and failure was defined as the presence of any residual stones.
      The stone-free rate was correlated with patient characteristics (age, sex and
      radiological renal picture) and stone features (site, side, length, width,
      nature, opacity and the presence of ureteral stents). Factors with a significant
      impact on the stone-free rate using the chi (2) test were further analyzed using
      multivariate analysis. RESULTS: Overall, the stone-free rate was 88.7%. Repeat
      treatment was required in 50.4% of cases. Post-ESWL complications were observed
      in 32 cases (3.4%), including static steinstrasse in 19 (2%). Auxiliary
      procedures were needed in 28 cases (3%). Using the chi (2) test, only three
      factors had a significant impact on the stone-free rate, namely stone site, the
      transverse diameter of the stone and the presence of a ureteral stent. The stone
      free rate was highest for stones located in the lumbar ureter (436/470; 92.8%)
      and lowest for those located in the pelvic ureter (268/324; 82.7%) (p = 0.0017).
      Stones with a transverse diameter of < or =1 cm were associated with a stone-free
      rate of 89.7% (715/797), compared to 83% (114/141) for those with a transverse
      diameter of >1 cm (p = 0.017). Non-stented patients had a stone-free rate of
      89.8% (732/815), compared to 81.3% (100/123) for stented patients (p = 0.006). On
      multivariate analysis, these three factors maintained their statistical
      significance. A logistic regression model was designed to estimate the
      probability of stone-free status after ESWL. CONCLUSION: The site and transverse
      diameter of the stone and the presence of a ureteral stent are the only
      significant predictors of success of ESWL therapy for ureteric stones.

PMID- 14594692
TI  - Stamey's abdominovaginal needle colposuspension for the correction of female
      genuine stress urinary incontinence--long-term results.
AB  - OBJECTIVES: To evaluate the long-term continence rate, subjective satisfaction
      and treatment-associated morbidity in a carefully selected group of patients
      undergoing Stamey bladder neck suspension. MATERIAL AND METHODS: We studied 24
      women with objectively validated genuine stress urinary incontinence (GSI) who
      were treated using the Stamey needle colposuspension method. Follow-up was
      performed by means of a questionnaire, a urodynamic assessment and a new
      standardized quantification test. Time to follow-up ranged from 28 to 100 months
      (mean 63 months). RESULTS: Of the 24 patients, 20 (83%) reported an improvement
      in clinical symptoms for a mean of 37 (range 12-84) months at the evaluation and
      10 (42%) were completely continent after the Stamey procedure. Four patients
      (17%) reported a poor outcome of the operation, but in only one case could this
      be related to recurrent GSI. Treatment-associated morbidity was low but the
      frequency of postoperative urgency symptoms was higher than that reported in
      other studies (21%). CONCLUSION: In a selected population of pure GSI patients
      with no demonstrable detrusor overactivity, the Stamey bladder neck suspension
      procedure appears a feasible therapeutic option with few complications.

PMID- 14594693
TI  - Extracorporeal magnetic stimulation for the treatment of stress and urge
      incontinence in women--results of 1-year follow-up.
AB  - OBJECTIVE: To evaluate the clinical efficacy of extracorporeal magnetic
      stimulation for the treatment of stress and urge urinary incontinence in women.
      MATERIAL AND METHODS: A total of 35 patients with stress incontinence and 17 with
      urge incontinence were enrolled in this study. All patients were evaluated by
      means of a detailed history of incontinence, a gynecologic examination, urine
      culture, urinary system ultrasound and a urodynamic study. All patients were
      asked to keep a 3-day voiding diary. A pad-weighing test was done for each
      patient at their first visit. For treatment, the patients were seated on a
      special chair containing a magnetic field generator. Pelvic floor muscle
      stimulation was performed for 20 min (10 min at 5 Hz and 10 min at 50 Hz) twice a
      week for a total of 8 weeks. The mean follow-up period was 16.8 months (range 12
      32 months). A total of 44 patients completed 1 year of follow-up and were re
      evaluated by means of voiding diary, pad-weighing test and cystometric study.
      RESULTS: Of the 44 patients, 11 (38%) with stress incontinence and 6 (40%) with
      urge incontinence were cured 1 year after the treatment. In addition, there was
      an improvement in symptoms in 12 patients (41%) in the stress group and 7 (47%)
      in the urge group. Pad weight was reduced from 15.4 to 5.8 g in the stress group
      and from 12.4 to 4.7 g in the urge group (p = 0.000 and 0.001, respectively).
      Mean Valsalva leak point pressure was increased from 87.3 +/- 15.9 to 118.0 +/-
      11.0 cmH (2) O in the stress group (p = 0.000). CONCLUSIONS: Extracorporeal
      magnetic stimulation therapy offers a non-invasive, effective and painless
      treatment for stress and urge incontinence in women.

PMID- 14594694
TI  - Is the risk of hypertension an indication for prophylactic nephrectomy in
      patients with unilateral multicystic dysplastic kidney?
AB  - OBJECTIVE: Surgery is still proposed by some as the treatment of choice for
      unilateral multicystic dysplastic kidney (UMCDK) because of the potential
      complications of hypertension, infection and malignant change. The purpose of
      this study is to demonstrate that the risk of hypertension does not justify
      routine nephrectomy. MATERIAL AND METHODS: We report 41 cases of UMCDK, treated
      between 1980 and 2001, 28 of whom were male (68%). Twenty-one patients were
      nephrectomized (51%). Twenty patients (49%) underwent clinical and ultrasound
      follow-up. Blood pressure was controlled every 3-4 months (over a period ranging
      from 9 months to 6 years) and an ultrasound scan was performed every 6 months
      during the first 2 years, and annually thereafter. RESULTS: In the patients
      treated non-operatively we observed a progressive spontaneous involution of their
      multicystic dysplastic kidneys and the total absence of complications such as
      hypertension or malignancy. CONCLUSION: It is reasonable to conservatively manage
      patients with UMCDK by means of repeated ultrasound examinations and blood
      pressure control.

PMID- 14594695
TI  - Thirty-day case fatality after nephrectomy in patients with liver cirrhosis--a
      Danish population-based cohort study.
AB  - OBJECTIVE: Previous studies have shown that patients with liver cirrhosis are at
      increased risk of death after a number of surgical procedures, but their risk of
      death after nephrectomy has not been examined. We compared the 30-day
      postoperative case fatality rate after nephrectomy in patients with liver
      cirrhosis with that of patients without liver cirrhosis using data from an
      established dataset. MATERIAL AND METHODS: Between 1 January, 1977 and 31
      December, 1993 we followed a population-based cohort of Danish liver cirrhosis
      patients in order to identify those who underwent nephrectomy. A control group of
      patients without liver cirrhosis who underwent nephrectomy during the same period
      was also identified. A logistic regression model was used to estimate the odds
      ratio of the 30-day case fatality rate of patients with liver cirrhosis relative
      to those without liver cirrhosis. The model was adjusted for age, sex,
      comorbidity and type of admission. The study was based entirely on data from the
      Danish National Registry of Patients. RESULTS: A total of 29/23 133 patients with
      liver cirrhosis underwent nephrectomy, and the control group comprised 582
      patients without liver cirrhosis. The 30-day case fatality rates were 24.1% and
      8.1%, respectively, yielding an adjusted odds ratio of 3.6 (95% CI 1.2-8.9) for
      patients with liver cirrhosis relative to those without liver cirrhosis. Male
      gender, high comorbidity and emergency admission were also associated with an
      increased risk of postoperative death. CONCLUSIONS: Nephrectomy in patients with
      liver cirrhosis carries an increased risk of postoperative death, but the lack of
      clinical data prevents us from suggesting guidelines for clinical management.

PMID- 14594696
TI  - How to predict nephropathy in type 1 diabetic patients.
AB  - OBJECTIVE: Do exaggerated increases in blood pressure and albuminuria during
      exercise occur earlier than microalbuminuria and which type of test is most
      predictive of diabetic nephropathy? MATERIAL AND METHODS: A total of 33 insulin
      dependent normoalbuminuric men (mean duration of diabetes 14 years; mean age 28
      years) and 34 age-matched apparently healthy control subjects were studied.
      Urinary albumin excretion, heart rate and blood pressure were measured during
      fixed workload (150 W) and fixed heart rate (155 beats/min) tests. Mean follow-up
      time was 13.1 +/- 3.2 years. A urinary albumin level in early-morning urine
      persistently >30 mg/l was considered a sign of diabetic nephropathy. RESULTS:
      Sixteen patients reached the endpoints of the study. Eleven had developed
      microalbuminuria and five macroalbuminuria (persistent levels of urinary albumin
      >300 mg/l). Of the latter patients, two needed dialysis. Systolic blood pressure
      and albumin excretion during the fixed heart rate test were higher in diabetic
      patients who developed signs of nephropathy than in control subjects and diabetic
      subjects with persistent healthy kidneys. Such differences were not found in the
      fixed workload test. There were no differences in glycated haemoglobin, blood
      pressure levels or albumin excretion at baseline between the two diabetic groups.
      CONCLUSIONS: To predict the development of diabetic nephropathy it seems
      important to choose a fixed heart rate test. High levels of systolic blood
      pressure in such a test were associated with the development of micro- and
      macroalbuminuria.

PMID- 14594697
TI  - Malignant metastatic perirenal schwannoma.
AB  - Only seven cases of malignant renal or perirenal schwannomas have previously been
      reported in the literature. Herein we report the case of a 74-year-old female
      with a previous history of malignant subcutaneous schwannoma and breast ductal
      adenocarcinoma who presented with a renal mass that was preoperatively diagnosed
      as a metastatic schwannoma. This is the first case of malignant perirenal
      schwannoma of metastatic origin.

PMID- 14594698
TI  - Impact of housing conditions on the health of the people at al-Ama'ri refugee
      camp in the West Bank of Palestine.
AB  - Al-Ama'ri camp is situated to the south of Ramallah city in the West Bank of
      Palestine. It is densely populated, with a total population of 4046, divided into
      760 households, on a surface area of 93 dunums (93000 m(2)). In this research,
      the relationship between the housing conditions at Ama'ri camp and the prevalence
      and incidence rates of upper respiratory tract diseases has been studied. The
      diseases and symptoms most encountered in winter, and those include: common cold,
      cough, pharyngitis, influenza, ear infection, asthma and bronchitis have been
      studied. It was found that these are diseases directly related to poor housing
      conditions. Cold housing, presence of dampness and moulds, dust and smoke,
      burning of biomass fuel, crowding, poor ventilation and inadequate lighting
      problems are commonly found in the houses of this refugee camp.

PMID- 14594699
TI  - Cardio-respiratory morbidity and long-term exposure to particulate air pollution.
AB  - To explore the long-term influence of particulate air pollution on cardio
      respiratory morbidity in the UK, a cross-sectional postal survey was conducted.
      Women were randomly selected from the electoral rolls of 11 wards in which Black
      Smoke measurements had been collected over at least 30 years. Our analyses
      included 1166 women aged 45 years or older who had lived within 5 miles of their
      current address for at least 30 years. After adjustment for potential confounders
      there was no clear increase in prevalence of productive cough or medically
      diagnosed ischaemic heart disease with long-term residence in places with higher
      levels of particulate pollution. The prevalence of asthma was lower in wards with
      the highest Black Smoke measurements (prevalence ratio 0.7, 95% CI 0.5 - 1.0).
      Our findings provide no indication that prolonged residence in places with
      relatively high levels of particulate pollution causes an important increase in
      cardio-respiratory morbidity. This is in contrast to observations in US studies.
      In view of this discordance, there is a need for further evaluation of the long
      term impact of particulate pollution on health in the UK.

PMID- 14594700
TI  - The regionality of campylobacteriosis seasonality in New Zealand.
AB  - New Zealand has one of the highest incidences of campylobacteriosis in the
      developed world, which leads a global trend of increasing notifications of
      Campylobacter infections over the last decade. Foodborne and waterborne
      transmission have been implicated as significant mechanisms in the complex
      ecology of the disease in New Zealand. We examined both regional and temporal
      variation in notification rates to gain some insight into the role of the New
      Zealand environments in modifying disease incidence. Firstly, there is a marked
      difference in the seasonality of campylobacteriosis between the North and South
      Islands of New Zealand. The Far North and much of the rural North Island were
      found to display relatively low summer incidence and small inter-seasonal
      variation. Secondly, there appears to be a dispersed grouping of North Island
      urban areas, including Auckland, Hamilton, Napier and their hinterlands as well
      as a few areas on the South Island that exhibit higher summer incidence and more
      seasonality than the first group. Thirdly, Christchurch, Dunedin, much of the
      South Island and the lower North Island cities of Wellington and Upper Hutt
      appear to experience the highest summer incidence and strongest inter-seasonal
      variation in New Zealand. These three broad groupings of campylobacteriosis
      seasonality, constructed using a principal components analysis, suggest that the
      importance of transmission routes may vary regionally in New Zealand. The
      observed variation in seasonal incidence indicates a complex ecology that is
      unlikely to be explained by a single dominant transmission route across these
      three groupings.

PMID- 14594702
TI  - Assessment of noise annoyance in three distinct communities living in close
      proximity to a UK regional airport.
AB  - Previous researchers have considered demographic variables relating to
      deprivation such as income, social status and home ownership, and their
      relationship with both community and individual reaction to environmental noise.
      These variables have been found not to be important. Intuitively this seems
      implausible and the findings of a recent African study increase the doubt. The
      present study aims to look at the effect of deprivation using an index of
      deprivation developed and adopted in a different context. A postal questionnaire
      was used to survey three communities around Birmingham International Airport, UK.
      The main selection criterion for these areas was the Townsend overall index of
      deprivation (ODI). The typical aircraft noise exposure levels for all of the
      survey areas were determined from the aircraft noise exposure contours provided
      by Birmingham International Airport. An overall response rate of 40% was achieved
      and it was found that the area of lowest deprivation (greatest affluence) has a
      significantly greater proportion of highly annoyed persons due to aircraft noise
      than the other two areas, with the lowest noise exposure category accounting for
      the significant difference. The differences in reaction are not explained by
      deprivation as measured by the ODI nor by other factors previously reported in
      the literature and by those that were measured in this study. However, a link
      between housing type and noise annoyance due to aircraft noise suggests an avenue
      for further research.

PMID- 14594701
TI  - Wessex shopping basket survey - a structured approach to local food sampling.
AB  - The shopping basket approach to food sampling, in which ready-to-eat food items
      from a shopping list were sampled at premises chosen at random, was adopted by 15
      Environmental Health Departments in the Wessex region. A total of 2037 samples
      were analysed over a 30-month period. The microbiological quality varied
      considerably between food categories, with gravy and stock samples giving the
      highest proportion of satisfactory results. Sliced meats, cooked rice and
      sandwiches gave the poorest overall results. Whilst the majority of
      unsatisfactory results were due to elevated levels of indicator organisms
      (Aerobic Colony Count, Enterobacteriaceae and Escherichia coli), unsatisfactory
      or potentially hazardous levels of pathogens (Staphylococcus aureus, Bacillus
      cereus, Clostridium perfringens or Listeria monocytogenes) were detected in 1% of
      samples. Salmonella was not detected in any sample. The shopping basket survey
      was considered to be a useful way of structuring local sampling, and the random
      selection of premises was found to be a considerable advantage over previous
      sampling plans. In addition, the survey drew attention to a number of
      microbiological problems with specific food types, leading to more detailed
      investigations.

PMID- 14594703
TI  - Genotoxic effects of vanadium pentoxide on human peripheral lymphocytes and
      mucosal cells of the upper aerodigestive tract.
AB  - In addition to tobacco and alcohol consumption, pollutants found in certain
      industries and in the environment play an important role in carcinogenesis in the
      upper aerodigestive tract. The aim of the present study was to investigate
      whether vanadium pentoxide may have a genotoxic effect on human mucosal cells and
      lymphocytes. The single cell microgel electrophoresis assay (Comet assay) was
      used to detect DNA damage induced by vanadium pentoxide in human nasal epithelia
      (n = 11) and in lymphocytes (n = 11). Mucosa was harvested from inferior nasal
      turbinates, while lymphocytes were obtained via venous puncture. Vanadium
      pentoxide was applied at concentrations of 0.06 mM, 0.12 mM, 0.24 mM, and 0.47
      mM. Aqua bidestillata served as solvent and negative control and N-methyl-N'
      nitro-N-nitrosoguanidine at 0.07 mM (MNNG) was used as positive control. The
      trypan blue exclusion test was applied to assess cytotoxicity. Whereas vanadium
      pentoxide induced dose-dependent DNA migration in lymphocytes, mucosal cells did
      not show comparable genotoxic effects. Cytotoxic effects allowed for viabilities
      exceeding 80%. The results indicate that vanadium pentoxide is capable of
      inducing single-strand-breaks and/or alkali-labile damage in the DNA of human
      lymphocytes. By contrast, mucosal cells proved not to be sensitive in this
      setting. Thus, a possible role of vanadium in the tumorigenesis of head and neck
      cancer appears unrelated to direct genotoxic effects.

PMID- 14594704
TI  - Codon adaptation index as a measure of dominating codon bias.
AB  - We propose a simple algorithm to detect dominating synonymous codon usage bias in
      genomes. The algorithm is based on a precise mathematical formulation of the
      problem that lead us to use the Codon Adaptation Index (CAI) as a 'universal'
      measure of codon bias. This measure has been previously employed in the specific
      context of translational bias. With the set of coding sequences as a sole source
      of biological information, the algorithm provides a reference set of genes which
      is highly representative of the bias. This set can be used to compute the CAI of
      genes of prokaryotic and eukaryotic organisms, including those whose functional
      annotation is not yet available. An important application concerns the detection
      of a reference set characterizing translational bias which is known to correlate
      to expression levels; in this case, the algorithm becomes a key tool to predict
      gene expression levels, to guide regulatory circuit reconstruction, and to
      compare species. The algorithm detects also leading-lagging strands bias, GC
      content bias, GC3 bias, and horizontal gene transfer. The approach is validated
      on 12 slow-growing and fast-growing bacteria, Saccharomyces cerevisiae,
      Caenorhabditis elegans and Drosophila melanogaster. AVAILABILITY:
      http://www.ihes.fr/~materials.

PMID- 14594705
TI  - Applying signal theory to the analysis of biomolecules.
AB  - MOTIVATION: The accumulation of sequence-related and other biological data for
      basic research and application purposes invites disaster. It appears very likely
      that neither traditional thinking nor current technologies (including their
      foreseeable evolutionary developments) will be able to cope with this ever
      intensifying situation. RESULTS: We present the detailed theoretical background
      for applying signal theory, as known from speech recognition and image analysis,
      to the analysis of biomolecules. The general scheme is as follows: biochemical
      and biophysical properties of biomolecules are used to model an n-dimensional
      signal which represents the entire information-bearing biomolecule. Such signals
      are used to search for biological principles, analogies or similarities between
      biomolecules. In a series of simple experiments (bacterial DNA, generation of
      real signals using melting enthalpies, detection filtering by convolution of
      signals) we have shown that the novel system for comparative analysis of the
      properties of information-bearing biomolecules works as in theory. SUPPLEMENTARY
      INFORMATION: http://genome.gbf.de/wavepaper.

PMID- 14594706
TI  - Development of an integrated laboratory information management system for the
      maize mapping project.
AB  - MOTIVATION: The development of an integrated genetic and physical map for the
      maize genome involves the generation of an enormous amount of data. Managing this
      data requires a system to aid in genotype scoring for different types of markers
      coming from both local and remote users. In addition, researchers need an
      efficient way to interact with genetic mapping software and with data files from
      automated DNA sequencing. They also need ways to manage primer data for mapping
      and sequencing and provide views of the integrated physical and genetic map and
      views of genetic map comparisons. RESULTS: The MMP-LIMS system has been used
      successfully in a high-throughput mapping environment. The genotypes from 957
      SSR, 1023 RFLP, 189 SNP, and 177 InDel markers have been entered and verified via
      MMP-LIMS. The system is flexible, and can be easily modified to manage data for
      other species. The software is freely available. AVAILABILITY: To receive a copy
      of the iMap or cMap software, please fill out the form on our website. The other
      MMP-LIMS software is freely available at
      http://www.maizemap.org/bioinformatics.htm.

PMID- 14594707
TI  - A novel strategy for microarray quality control using Bayesian networks.
AB  - MOTIVATION: High-throughput microarray technologies enable measurements of the
      expression levels of thousands of genes in parallel. However, microarray
      printing, hybridization and washing may create substantial variability in the
      quality of the data. As erroneous measurements may have a drastic impact on the
      results by disturbing the normalization schemes and by introducing expression
      patterns that lead to incorrect conclusions, it is crucial to discard low quality
      observations in the early phases of a microarray experiment. A typical microarray
      experiment consists of tens of thousands of spots on a microarray, making manual
      extraction of poor quality spots impossible. Thus, there is a need for a reliable
      and general microarray spot quality control strategy. RESULTS: We suggest a novel
      strategy for spot quality control by using Bayesian networks, which contain many
      appealing properties in the spot quality control context. We illustrate how a non
      linear least squares based Gaussian fitting procedure can be used in order to
      extract features for a spot on a microarray. The features we used in this study
      are: spot intensity, size of the spot, roundness of the spot, alignment error,
      background intensity, background noise, and bleeding. We conclude that Bayesian
      networks are a reliable and useful model for microarray spot quality assessment.
      SUPPLEMENTARY INFORMATION: http://sigwww.cs.tut.fi/TICSP/SpotQuality/.

PMID- 14594708
TI  - Inferring protein interactions from phylogenetic distance matrices.
AB  - Finding the interacting pairs of proteins between two different protein families
      whose members are known to interact is an important problem in molecular biology.
      We developed and tested an algorithm that finds optimal matches between two
      families of proteins by comparing their distance matrices. A distance matrix
      provides a measure of the sequence similarity of proteins within a family. Since
      the protein sets of interest may have dozens of proteins each, the use of an
      efficient approximate solution is necessary. Therefore the approach we have
      developed consists of a Metropolis Monte Carlo optimization algorithm which
      explores the search space of possible matches between two distance matrices. We
      demonstrate that by using this algorithm we are able to accurately match
      chemokines and chemokine-receptors as well as the tgfbeta family of ligands and
      their receptors.

PMID- 14594709
TI  - Extraction of protein interaction information from unstructured text using a
      context-free grammar.
AB  - MOTIVATION: As research into disease pathology and cellular function continues to
      generate vast amounts of data pertaining to protein, gene and small molecule
      (PGSM) interactions, there exists a critical need to capture these results in
      structured formats allowing for computational analysis. Although many efforts
      have been made to create databases that store this information in computer
      readable form, populating these sources largely requires a manual process of
      interpreting and extracting interaction relationships from the biological
      research literature. Being able to efficiently and accurately automate the
      extraction of interactions from unstructured text, would greatly improve the
      content of these databases and provide a method for managing the continued growth
      of new literature being published. RESULTS: In this paper, we describe a system
      for extracting PGSM interactions from unstructured text. By utilizing a lexical
      analyzer and context free grammar (CFG), we demonstrate that efficient parsers
      can be constructed for extracting these relationships from natural language with
      high rates of recall and precision. Our results show that this technique achieved
      a recall rate of 83.5% and a precision rate of 93.1% for recognizing PGSM names
      and a recall rate of 63.9% and a precision rate of 70.2% for extracting
      interactions between these entities. In contrast to other published techniques,
      the use of a CFG significantly reduces the complexities of natural language
      processing by focusing on domain specific structure as opposed to analyzing the
      semantics of a given language. Additionally, our approach provides a level of
      abstraction for adding new rules for extracting other types of biological
      relationships beyond PGSM relationships. AVAILABILITY: The program and corpus are
      available by request from the authors.

PMID- 14594710
TI  - Protein structural class identification directly from NMR spectra using averaged
      chemical shifts.
AB  - Knowledge of the three-dimensional structure of proteins is integral to
      understanding their functions, and a necessity in the era of proteomics. A wide
      range of computational methods is employed to estimate the secondary, tertiary,
      and quaternary structures of proteins. Comprehensive experimental methods, on the
      other hand, are limited to nuclear magnetic resonance (NMR) and X-ray
      crystallography. The full characterization of individual structures, using either
      of these techniques, is extremely time intensive. The demands of high throughput
      proteomics necessitate the development of new, faster experimental methods for
      providing structural information. As a first step toward such a method, we
      explore the possibility of determining the structural classes of proteins
      directly from their NMR spectra, prior to resonance assignment, using averaged
      chemical shifts. This is achieved by correlating NMR-based information with
      empirical structure-based information available in widely used electronic
      databases. The results are analyzed statistically for their significance. The
      robustness of the method as a structure predictor is probed by applying it to a
      set of proteins of unknown structure. Our results show that this NMR-based method
      can be used as a low-resolution tool for protein structural class identification.

PMID- 14594712
TI  - Linear regression and two-class classification with gene expression data.
AB  - MOTIVATION: Using gene expression data to classify (or predict) tumor types has
      received much research attention recently. Due to some special features of gene
      expression data, several new methods have been proposed, including the weighted
      voting scheme of Golub et al., the compound covariate method of Hedenfalk et al.
      (originally proposed by Tukey), and the shrunken centroids method of Tibshirani
      et al. These methods look different and are more or less ad hoc. RESULTS: We
      point out a close connection of the three methods with a linear regression model.
      Casting the classification problem in the general framework of linear regression
      naturally leads to new alternatives, such as partial least squares (PLS) methods
      and penalized PLS (PPLS) methods. Using two real data sets, we show the
      competitive performance of our new methods when compared with the other three
      methods.

PMID- 14594711
TI  - Venn Mapping: clustering of heterologous microarray data based on the number of
      co-occurring differentially expressed genes.
AB  - MOTIVATION: To evaluate microarray data, clustering is widely used to group
      biological samples or genes. However, problems arise when comparing heterologous
      databases. As the clustering algorithm searches for similarities between
      experiments, it will most likely first separate the data sets, masking
      relationships that exist between samples from different databases. RESULTS: We
      developed a program, Venn Mapper, to calculate the statistical significance of
      the number of co-occurring differentially expressed genes in any of the two
      experiments. For proof of principle, we analysed a heterologous data set of 170
      microarrays including breast and prostate cancer microarray analyses. Significant
      overlap was found in an unsupervised analysis between metastasized prostate
      cancer and metastasized breast cancer and BRCA mutated breast cancer. A
      comparison between single microarray data and the averaged breast and prostate
      data sets was also evaluated. This analysis suggests that genes expressed higher
      in stromal cells are also implicated in metastatic prostate cancer and BRCA
      mutated breast cancer. The Venn Mapper program identifies overlaps between
      samples from heterologous data sets and directly extracts the genes responsible
      for the overlap. From this information novel biological hypotheses may be
      addressed. AVAILABILITY: Venn Mapper is freely available on
      http://www.erasmusmc.nl/gatcplatform. SUPPLEMENTARY INFORMATION:
      http://www.erasmusmc.nl/gatcplatform/vennmapper.html.

PMID- 14594713
TI  - Markovian negentropies in bioinformatics. 1. A picture of footprints after the
      interaction of the HIV-1 Psi-RNA packaging region with drugs.
AB  - MOTIVATION: Many experts worldwide have highlighted the potential of RNA
      molecules as drug targets for the chemotherapeutic treatment of a range of
      diseases. In particular, the molecular pockets of RNA in the HIV-1 packaging
      region have been postulated as promising sites for antiviral action. The
      discovery of simpler methods to accurately represent drug-RNA interactions could
      therefore become an interesting and rapid way to generate models that are
      complementary to docking-based systems. RESULTS: The entropies of a vibrational
      Markov chain have been introduced here as physically meaningful descriptors for
      the local drug-nucleic acid complexes. A study of the interaction of the
      antibiotic Paromomycin with the packaging region of the RNA present in type-1 HIV
      has been carried out as an illustrative example of this approach. A linear
      discriminant function gave rise to excellent discrimination among 80.13% of
      interacting/non-interacting sites. More specifically, the model classified 36/45
      nucleotides (80.0%) that interacted with paromomycin and, in addition, 85/106
      (80.2%) footprinted (non-interacting) sites from the RNA viral sequence were
      recognized. The model showed a high Matthews' regression coefficient (C = 0.64).
      The Jackknife method was also used to assess the stability and predictability of
      the model by leaving out adenines, C, G, or U. Matthews' coefficients and overall
      accuracies for these approaches were between 0.55 and 0.68 and 75.8 and 82.7,
      respectively. On the other hand, a linear regression model predicted the local
      binding affinity constants between a specific nucleotide and the aforementioned
      antibiotic (R2 = 0.83,Q2 = 0.825). These kinds of models may play an important
      role either in the discovery of new anti-HIV compounds or in the elucidation of
      their mode of action. AVAILABILITY: On request from the corresponding author
      (humbertogd@cbq.uclv.edu.cu or humbertogd@navegalia.com).

PMID- 14594714
TI  - A Bayesian missing value estimation method for gene expression profile data.
AB  - MOTIVATION: Gene expression profile analyses have been used in numerous studies
      covering a broad range of areas in biology. When unreliable measurements are
      excluded, missing values are introduced in gene expression profiles. Although
      existing multivariate analysis methods have difficulty with the treatment of
      missing values, this problem has received little attention. There are many
      options for dealing with missing values, each of which reaches drastically
      different results. Ignoring missing values is the simplest method and is
      frequently applied. This approach, however, has its flaws. In this article, we
      propose an estimation method for missing values, which is based on Bayesian
      principal component analysis (BPCA). Although the methodology that a
      probabilistic model and latent variables are estimated simultaneously within the
      framework of Bayes inference is not new in principle, actual BPCA implementation
      that makes it possible to estimate arbitrary missing variables is new in terms of
      statistical methodology. RESULTS: When applied to DNA microarray data from
      various experimental conditions, the BPCA method exhibited markedly better
      estimation ability than other recently proposed methods, such as singular value
      decomposition and K-nearest neighbors. While the estimation performance of
      existing methods depends on model parameters whose determination is difficult,
      our BPCA method is free from this difficulty. Accordingly, the BPCA method
      provides accurate and convenient estimation for missing values. AVAILABILITY: The
      software is available at http://hawaii.aist-nara.ac.jp/~shige-o/tools/.

PMID- 14594715
TI  - Kernel hierarchical gene clustering from microarray expression data.
AB  - MOTIVATION: Unsupervised analysis of microarray gene expression data attempts to
      find biologically significant patterns within a given collection of expression
      measurements. For example, hierarchical clustering can be applied to expression
      profiles of genes across multiple experiments, identifying groups of genes that
      share similar expression profiles. Previous work using the support vector machine
      supervised learning algorithm with microarray data suggests that higher-order
      features, such as pairwise and tertiary correlations across multiple experiments,
      may provide significant benefit in learning to recognize classes of co-expressed
      genes. RESULTS: We describe a generalization of the hierarchical clustering
      algorithm that efficiently incorporates these higher-order features by using a
      kernel function to map the data into a high-dimensional feature space. We then
      evaluate the utility of the kernel hierarchical clustering algorithm using both
      internal and external validation. The experiments demonstrate that the kernel
      representation itself is insufficient to provide improved clustering performance.
      We conclude that mapping gene expression data into a high-dimensional feature
      space is only a good idea when combined with a learning algorithm, such as the
      support vector machine that does not suffer from the curse of dimensionality.
      AVAILABILITY: Supplementary data at www.cs.columbia.edu/compbio/hiclust. Software
      source code available by request.

PMID- 14594716
TI  - iMap: a database-driven utility to integrate and access the genetic and physical
      maps of maize.
AB  - MOTIVATION: Because of the unique biological features, a bioinformatic platform
      for the integrated genetic and physical map of maize is required for storing,
      integrating, accessing and visualizing the underlying data. RESULTS: The goal of
      the Maize Mapping Project is to develop a fully integrated genetic and physical
      map for maize. To display this integrated map, we have developed iMap. iMap has
      three main components: a relational database (iMapDB), a map graphic browser
      (iMap Viewer) and a search utility (iMap Search). iMapDB is populated with
      current genetic and physical map data, describing relationships among genetic
      loci, molecular markers and bacterial artificial chromosome (BAC) contigs. The
      database also contains integrated information produced by applying a set of
      anchoring rules to assign BAC contigs to specific locations on the genetic map.
      The iMap Viewer and iMap Search functions are combined in the user interface to
      allow viewing and retrieving many types of genetic and physical map data. The
      iMap Viewer features side-by-side chromosome-based displays of the genetic map
      and associated BAC contigs. For each genetic locus, information about marker type
      or contig can be viewed via pop-up windows that feature links to external data
      resources. Searches can be conducted for genetic locus, probe or sequence
      accession number; search results include relevant map positions, anchored BAC
      contigs and links to the graphical display of relevant chromosomes. iMap can be
      accessed at http://www.maizemap.org AVAILABILITY: The iMap utility package is
      available for non-commercial use upon request from the authors.

PMID- 14594717
TI  - Inhomogeneous molecular density: reference packing densities and distribution of
      cavities within proteins.
AB  - MOTIVATION: There is no consensus in the literature about how the deepest
      portions of protein structures are packed. Using an improved Voronoi procedure,
      we calculate reference packing densities for different regions in the protein
      interior. Furthermore, we want to clarify where cavities are located. RESULTS:
      Sets of reference packing densities are provided for regions in proteins that
      differ in their distance to the surface and to internal cavities, supplementing
      previous data. Packing in the protein interior is tight but generally
      inhomogeneous. There are about 4.4 cavities per 100 amino acids in protein
      structures, they occur in all regions, most frequently in a depth of 2.5-3.6 A
      underneath the Connolly surface. However, the deepest protein regions have a
      lower mean packing density than circumjacent regions, because more contacts to
      cavities occur in the core. AVAILABILITY/SUPPLEMENTARY INFORMATION: Calculation
      software and detailed packing data are available on request.

PMID- 14594718
TI  - A new sequence distance measure for phylogenetic tree construction.
AB  - MOTIVATION: Most existing approaches for phylogenetic inference use multiple
      alignment of sequences and assume some sort of an evolutionary model. The
      multiple alignment strategy does not work for all types of data, e.g. whole
      genome phylogeny, and the evolutionary models may not always be correct. We
      propose a new sequence distance measure based on the relative information between
      the sequences using Lempel-Ziv complexity. The distance matrix thus obtained can
      be used to construct phylogenetic trees. RESULTS: The proposed approach does not
      require sequence alignment and is totally automatic. The algorithm has
      successfully constructed consistent phylogenies for real and simulated data sets.
      AVAILABILITY: Available on request from the authors.

PMID- 14594719
TI  - An unsupervised hierarchical dynamic self-organizing approach to cancer class
      discovery and marker gene identification in microarray data.
AB  - MOTIVATION: Current Self-Organizing Maps (SOMs) approaches to gene expression
      pattern clustering require the user to predefine the number of clusters likely to
      be expected. Hierarchical clustering methods used in this area do not provide
      unique partitioning of data. We describe an unsupervised dynamic hierarchical
      self-organizing approach, which suggests an appropriate number of clusters, to
      perform class discovery and marker gene identification in microarray data. In the
      process of class discovery, the proposed algorithm identifies corresponding sets
      of predictor genes that best distinguish one class from other classes. The
      approach integrates merits of hierarchical clustering with robustness against
      noise known from self-organizing approaches. RESULTS: The proposed algorithm
      applied to DNA microarray data sets of two types of cancers has demonstrated its
      ability to produce the most suitable number of clusters. Further, the
      corresponding marker genes identified through the unsupervised algorithm also
      have a strong biological relationship to the specific cancer class. The algorithm
      tested on leukemia microarray data, which contains three leukemia types, was able
      to determine three major and one minor cluster. Prediction models built for the
      four clusters indicate that the prediction strength for the smaller cluster is
      generally low, therefore labelled as uncertain cluster. Further analysis shows
      that the uncertain cluster can be subdivided further, and the subdivisions are
      related to two of the original clusters. Another test performed using colon
      cancer microarray data has automatically derived two clusters, which is
      consistent with the number of classes in data (cancerous and normal).
      AVAILABILITY: JAVA software of dynamic SOM tree algorithm is available upon
      request for academic use. SUPPLEMENTARY INFORMATION: A comparison of rectangular
      and hexagonal topologies for GSOM is available from
      http://www.mame.mu.oz.au/mechatronics/journalinfo/Hsu2003supp.pdf

PMID- 14594720
TI  - SNP cherry picker: maximizing the chance of finding an association with a disease
      SNP.
AB  - The high cost of genotyping single nucleotide polymorphisms (SNPs) generally
      prohibits the systematic mapping of entire genetic linkage regions in order to
      find the polymorphisms associated with increased risk of disease. In practice,
      SNPs are selected at approximately equal spacing across the linkage region to try
      to locate a SNP lying in the haplotype block of the disease SNP. The size of the
      haplotype block may not be known, however, and SNPs taken from public domain
      sources may not in fact be polymorphic. Our program will choose a subset of the
      SNPs in a linkage region so as to maximize the expected proportion of the
      sequence that lies within a given distance of a real SNP. AVAILABILITY: The
      software is available, free of charge, for academic use on request from the
      authors. SUPPLEMENTARY INFORMATION: www.oxagen.co.uk

PMID- 14594721
TI  - MetaFluxNet: the management of metabolic reaction information and quantitative
      metabolic flux analysis.
AB  - SUMMARY: MetaFluxNet is a program package for managing information on the
      metabolic reaction network and for quantitatively analyzing metabolic fluxes in
      an interactive and customized way. It allows users to interpret and examine
      metabolic behavior in response to genetic and/or environmental modifications. As
      a result, quantitative in silico simulations of metabolic pathways can be carried
      out to understand the metabolic status and to design the metabolic engineering
      strategies. The main features of the program include a well-developed model
      construction environment, user-friendly interface for metabolic flux analysis
      (MFA), comparative MFA of strains having different genotypes under various
      environmental conditions, and automated pathway layout creation. AVAILABILITY:
      http://mbel.kaist.ac.kr/ SUPPLEMENTARY INFORMATION: A manual for MetaFluxNet is
      available as PDF file.

PMID- 14594722
TI  - LDA--a java-based linkage disequilibrium analyzer.
AB  - We describe an integrated java-based program that provides elaborate graphic and
      plain-text output of pairwise linkage disequilibrium (LD) analysis of single
      nucleotide polymorphisms genotypic data. It is most suitable for molecular
      geneticists, who are focusing on LD measures estimation, statistical significance
      test and extent prediction. AVAILABILITY: The software is available at:
      http://www.chgb.org.cn/lda/lda.htm. SUPPLEMENTARY INFORMATION: Detailed
      tutorials, LDA help system and examples are distributed within LDA software. For
      Macintosh OS X user, the Jre version 1.4 can be downloaded from
      http://connect.apple.com.

PMID- 14594723
TI  - The UAB Proteomics Database.
AB  - SUMMARY: The University of Alabama at Birmingham (UAB) Proteomics Database (UPD)
      (http://www.uab.edu/proteinmenu) was created to provide a repository for the
      storage and linkage of two-dimensional (2D) gel images and the associated
      information obtained through mass spectrometry analysis of the proteins excised
      from the 2D gels in a manner similar to the SWISS-2DPAGE database and the
      Stanford Microarray Database. This was accomplished through the development of a
      web interface, a relational database, image maps and hyperlinks stored in the
      database. In addition to the internally generated data, UPD provides links to the
      National Center for Biotechnology Information via accession number hyperlinks.
      UPD currently contains information on 44 individual proteins derived from four
      experiments conducted by four UAB faculty members. Images of the gels from which
      each of these proteins was isolated are accessed by hyperlinks embedded in the
      database. AVAILABILITY: The UAB Proteomics Database can be accessed at
      http://www.uab.edu/proteinmenu.

PMID- 14594724
TI  - RED-T: utilizing the Ratios of Evolutionary Distances for determination of
      alternative phylogenetic events.
AB  - SUMMARY: RED-T is a Java application for phylogenetic analysis based on a unique
      method, RED, that utilizes the ratios of evolutionary distances E(d) to
      distinguish between alternative evolutionary histories. RED-T allows the user to
      examine if any given experimental gene shares the same evolutionary history as
      the designated control gene(s). Moreover, the tool detects any differences in
      evolutionary history and allows the user to examine comparisons of E(d) for a
      likely explanation. Lateral gene transfer, which may have a significant influence
      in organismal evolution is one mechanism that could explain the findings of these
      RED-T analyses. AVAILABILITY: The application is available online at
      http://www.arches.uga.edu/~whitman/RED.

PMID- 14594725
TI  - Pathway studio--the analysis and navigation of molecular networks.
AB  - SUMMARY: PathwayAssist is a software application developed for navigation and
      analysis of biological pathways, gene regulation networks and protein interaction
      maps. It comes with the built-in natural language processing module MedScan and
      the comprehensive database describing more than 100 000 events of regulation,
      interaction and modification between proteins, cell processes and small
      molecules. AVAILABILITY: PathwayAssist is available for commercial licensing from
      Ariadne Genomics, Inc. The light version with limited functionality will be
      available for free for academic users at www.ariadnegenomics.com/downloads/.

PMID- 14594726
TI  - GARBAN: genomic analysis and rapid biological annotation of cDNA microarray and
      proteomic data.
AB  - SUMMARY: Genomic Analysis and Rapid Biological ANnotation (GARBAN) is a new tool
      that provides an integrated framework to analyze simultaneously and compare
      multiple data sets derived from microarray or proteomic experiments. It carries
      out automated classifications of genes or proteins according to the criteria of
      the Gene Ontology Consortium at a level of depth defined by the user.
      Additionally, it performs clustering analysis of all sets based on functional
      categories or on differential expression levels. GARBAN also provides graphical
      representations of the biological pathways in which all the genes/proteins
      participate. AVAILABILITY: http://garban.tecnun.es.

PMID- 14594727
TI  - RankViaContact: ranking and visualization of amino acid contacts.
AB  - SUMMARY: RankViaContact is a web service for calculation of residue-residue
      contact energies in proteins based on a coarse-grained model, and for
      visualization of interactions. The service provides information about ranked
      contact energies of residues, coordination numbers and the relative solvent
      accessibility of selected residues, as well as sequence and structure
      information. The program can be used to design stabilizing mutations, to analyze
      residue-residue contacts and to study the consequences of mutations.
      AVAILABILITY: http://bioinf.uta.fi/Rank.htm.

PMID- 14594728
TI  - Electrophoretic data classification for phylogenetics and biostatistics.
AB  - SUMMARY: This paper presents ClassMaker, a macro of MS Excel able to classify
      continuous data of molecular weight data as binary (1/0) values. The output is
      represented by a binary matrix, which can be introduced in every software
      application for phylogenetics or multivariate statistics. This application is
      designed in order to be a link between image analysis programs and statistical or
      phylogenetic applications, in order to produce a complete series of free programs
      able to carry out the complete analysis from the gel to the dendrogram.
      AVAILABILITY: ClassMaker is freely available from
      http://www.agr.unipg.it/cardinali/index.html, where a list of the URLs from which
      programs of image analysis, statistics and phylogenetics can be freely
      downloaded.

PMID- 14594729
TI  - Isolation of rodent airway epithelial cell proteins facilitates in vivo
      proteomics studies of lung toxicity.
AB  - Recent developments in genomics, proteomics, and metabolomics hold substantial
      promise for understanding cellular responses to toxicants. Gene expression
      profiling is now considered standard procedure, but numerous publications
      reporting a lack of correlation between mRNA and protein expression emphasize the
      importance of conducting parallel proteomics studies. The cellular complexity of
      the lung presents great challenges for in vivo proteomics, and improved isolation
      methods for proteins from specific lung cell phenotypes are required. To address
      this issue, we have developed a novel method for isolation of rodent airway
      epithelial cell proteins that facilitates in vivo proteomics studies of two
      target-cell pheno-types of the lung, Clara cells and ciliated cells. The airway
      epithelial cell proteins are reproducibly solubilized, leaving the underlying
      basement membrane and smooth muscle intact as shown by histopathological
      analyses. The method yields epithelial cell-specific proteins in fivefold higher
      concentrations and reduces the yield of nonepithelial cell proteins 13-fold
      compared with homogenates from microdissected airways. In addition, 36% more
      protein spots were detectable by two-dimensional gel electrophoresis.

PMID- 14594730
TI  - Role of human neutrophil peptides in lung inflammation associated with alpha1
      antitrypsin deficiency.
AB  - Individuals with alpha(1)-antitrypsin (alpha(1)-AT) deficiency are at risk for
      early-onset destructive lung disease as a result of insufficient lower
      respiratory tract alpha(1)-AT and an increased burden of neutrophil products such
      as elastase. Human neutrophil peptides (HNP), the most abundant protein component
      of neutrophil azurophilic granules, represent another potential inflammatory
      component in lung disease characterized by increased numbers of activated or
      deteriorating neutrophils. The purpose of this study was to determine the role of
      HNP in lower respiratory tract inflammation and destruction occuring in alpha(1)
      AT deficiency. alpha(1)-AT-deficient individuals (n = 33) and healthy control
      subjects (n = 21) were evaluated by bronchoalveolar lavage. HNP concentrations
      were significantly higher in alpha(1)-AT-deficient individuals (1,976 +/- 692 vs.
      29 +/- 12 nM, P < 0.0001), and levels correlated with markers of neutrophil
      mediated lung inflammation. In vitro, HNP produced a dose-dependent cytotoxic
      effect on alveolar macrophages and stimulated production of the potent neutrophil
      chemoattractants leukotriene B(4) and interleukin-8 by alveolar macrophages, with
      a 6- to 10-fold increase in chemoattractant production over negative control
      cultures (P < 0.05). A synergistic effect was noted between HNP and neutrophil
      elastase with regard to leukotriene B(4) production. Importantly, the
      proinflammatory effects of HNP were blocked by alpha(1)-AT. HNP likely play an
      important role in amplifying and maintaining neutrophil-mediated inflammation in
      the lungs.

PMID- 14594732
TI  - Toward a biochemistry of mind?

PMID- 14594731
TI  - Calorie-related rapid onset of alveolar loss, regeneration, and changes in mouse
      lung gene expression.
AB  - Calorie restriction, followed by ad libitum refeeding, results, respectively, in
      loss and regeneration of pulmonary alveoli. We now show 35% of alveoli are lost
      within 72 h of onset of calorie restriction ((2/3) decreased daily chow intake),
      and an additional 12% of alveoli are lost over a subsequent 12 days of calorie
      restriction. Tissue necrosis was not seen. Within 72 h of refeeding, after 15
      days of calorie restriction, the number of alveoli returns to precalorie
      restriction values. Microarray lung gene profiling, in conjunction with Western
      and RNase protection assay, demonstrate an increase of granzyme and caspase gene
      expression 2-3 h after onset of calorie restriction. By 12 h, granzyme and
      caspase expression is no longer increased, but tumor necrosis factor death
      receptor expression is elevated. At 336 h, Fas death receptor expression is
      increased. Because granzymes are found only in cytotoxic lymphocytes (CTLs) and
      natural killer (NK) cells, we suggest calorie restriction activates these cells,
      initiating a series of molecular events that results in alveolar destruction. The
      evidence of involvement of CTLs and NK cells and the absence of necrosis are
      similar to alveolar destruction in chronic obstructive pulmonary disease.

PMID- 14594734
TI  - Which SSRI? A meta-analysis of pharmacotherapy trials in pediatric obsessive
      compulsive disorder.
AB  - OBJECTIVE: The authors conducted a meta-analysis of published randomized,
      controlled medication trials in children and adolescents with obsessive
      compulsive disorder (OCD) to assess evidence for differential efficacy based on
      type of drug, study design, and outcome measure. METHOD: A systematic literature
      search was performed for articles pertaining to the pharmacological treatment of
      pediatric and/or adolescent OCD. All baseline, posttreatment, and change scores
      with standard deviations reported in each study were included in the analyses.
      Effect sizes for dependent measures were expressed as standardized mean
      differences. The analysis included data on efficacy for four selective serotonin
      reuptake inhibitors (SSRIs) (paroxetine, fluoxetine, fluvoxamine, and sertraline)
      and clomipramine, four study designs, four dependent outcome measures, and two
      types of outcome scores (change and posttreatment scores). Multivariate
      regression was performed to assess the degree to which the effect sizes varied
      with the methodological features of each study. RESULTS: Twelve studies with a
      total of 1,044 participants met all inclusion criteria for the analysis. The
      pooled standardized mean difference for the results of all studies was 0.46 and
      showed a highly significant difference between drug and placebo treatment. Only
      one of the four outcome measures evaluated was not sensitive to change with
      treatment. A multivariate regression analysis of drug effect with other variables
      controlled showed that clomipramine was significantly superior to each of the
      SSRIs but that the SSRIs were comparably effective. CONCLUSIONS: Although highly
      significant, the overall effect sizes for medication were modest. Similarities
      and differences between the variables studied that emerged in the meta-analysis
      may have implications for both clinical care and future research.

PMID- 14594733
TI  - Variables that affect the clinical use and abuse of methylphenidate in the
      treatment of ADHD.
AB  - OBJECTIVE: Methylphenidate, the most common treatment for attention deficit
      hyperactivity disorder (ADHD), increases extracellular dopamine in the brain,
      which is associated with its reinforcing as well as its therapeutic effects. The
      authors evaluated variables that distinguish these two properties. METHOD: The
      brain imaging and clinical literatures were analyzed to identify variables that
      contribute to the abuse liability as well as to the clinical efficacy of
      methylphenidate. RESULTS: Four variables were identified. 1) Dose--there is a
      threshold for methylphenidate-induced dopamine increases to be perceived as
      reinforcing and to produce therapeutic effects. 2) Pharmacokinetics--the
      reinforcing effects of methylphenidate are associated with rapid changes in serum
      concentrations and presumably fast dopamine increases (as achieved with
      intravenous injection or insufflation), whereas the therapeutic effects are
      associated with slowly ascending serum concentrations and presumably smoothly
      rising dopamine levels (as achieved with oral administration). 3) Individual
      differences--sensitivity to methylphenidate varies across individuals and sets a
      threshold for blood and brain levels required for reinforcing effects (drug
      liking) and for therapeutic effects (symptom reduction). 4) Context--the effects
      of methylphenidate are modulated by different settings in abuse (rituals of self
      administration and powerful conditioning) and in clinical use (external demands
      of low activity and focused attention). CONCLUSIONS: Reinforcing effects occur
      when methylphenidate elicits large and fast dopamine increases that mimic those
      of phasic dopamine cell firing, whereas therapeutic effects occur when
      methylphenidate elicits slow, steady-state dopamine increases that mimic those of
      tonic firing. Thus, the characteristics of clinical use (low doses administered
      orally and titrated for therapeutic effects) constrain methylphenidate's abuse.

PMID- 14594735
TI  - Schizophrenia, VII: defining the neurobiology of risk factors.

PMID- 14594737
TI  - Adult baby syndrome.

PMID- 14594738
TI  - Sandor Ferenczi, M.D, 1873-1933.

PMID- 14594739
TI  - In search of the emotional self: an fMRI study using positive and negative
      emotional words.
AB  - OBJECTIVE: The authors used functional magnetic resonance imaging (fMRI) to
      define the neural regions mediating self-referential processing of emotional
      stimuli and to explore how these regions are influenced by the emotional valence
      of the stimulus. METHOD: Ten healthy subjects were presented with words
      describing positive and negative personality traits during fMRI scanning in three
      different conditions. In the self-referential processing condition, subjects
      judged whether they thought each trait described them. In the other-referential
      processing condition, subjects judged whether the stimulus described a generally
      desirable trait. In the letter-recognition control condition, subjects indicated
      whether the word contained a specific target letter. RESULTS: The self
      referential condition induced bilateral activation in the dorsomedial prefrontal
      cortex, whereas the other-referential condition induced activation in lateral
      prefrontal areas. Activation in the right dorsomedial prefrontal cortex was
      unique to the self-referential condition regardless of the valence of the words,
      although positive words produced a more robust activation than did negative
      words. In the self-referential condition, differences between the processing of
      positive and negative words were seen in regions outside the medial frontal
      cortex, with reductions in the insula, temporal and occipital regions, and
      inferior parietal regions associated with negative words. CONCLUSIONS: A widely
      distributed network of brain areas contributes to emotional processing. Among
      these regions, the right dorsomedial prefrontal cortex is one main area mediating
      self-reference. By providing a personal perspective in the evaluation of
      emotional stimuli, the right dorsomedial prefrontal cortex may mediate cognitive
      processes, such as those involved in psychotherapy, that guide self-regulation of
      emotional experience.

PMID- 14594740
TI  - Functional neuroanatomy of grief: an FMRI study.
AB  - OBJECTIVE: In this study the authors examined the functional neuroanatomy of
      grief, which to their knowledge has not been studied previously in functional
      neuroimaging research. METHOD: Grief was elicited in eight bereaved women through
      photographs of the deceased versus a stranger, combined with words specific to
      the death event versus neutral words. Use of both pictures and words resulted in
      a 2x2 factorial design. RESULTS: Three brain regions were independently activated
      by the picture and word factors: posterior cingulate cortex, medial/superior
      frontal gyrus, and cerebellum. The two factors also activated distinct regions:
      for the picture factor, they were the cuneus, superior lingual gyrus, insula,
      dorsal anterior cingulate cortex, inferior temporal gyrus, and fusiform gyrus;
      and for the word factor, they were the precuneus, precentral gyrus, midbrain, and
      vermis. The interaction of the two factors showed significant activation in the
      cerebellar vermis. CONCLUSIONS: Grief is mediated by a distributed neural network
      that subserves affect processing, mentalizing, episodic memory retrieval,
      processing of familiar faces, visual imagery, autonomic regulation, and
      modulation/coordination of these functions. This neural network may account for
      the unique, subjective quality of grief and provide new leads in understanding
      the health consequences of grief and the neurobiology of attachment.

PMID- 14594741
TI  - Visualizing how one brain understands another: a PET study of theory of mind.
AB  - OBJECTIVE: Theory of mind (TOM), or "mentalizing," refers to the ability to
      attribute mental states to self and others. Inferring what people are thinking
      and feeling is an important aspect of human social interaction, and it is also an
      important aspect of both psychiatric diagnosis and treatment. The authors
      conducted a positron emission tomography (PET) study to examine the neural
      substrates of TOM, using a task that mimics real-life social interaction. METHOD:
      Thirteen healthy volunteers underwent [(15)O]H(2)O PET while performing an
      experimental task and a control task. During the experimental task they created a
      "story" about the mental state of a stranger whom they imagined encountering on a
      park bench. During the control task, they read aloud a story requiring no mental
      state attribution. RESULTS: The TOM task activated an extensive neural network
      that included the medial frontal cortex, the superior frontal cortex, the
      anterior and retrosplenial cingulate, and the anterior temporal pole; most of
      these activations were limited to the left hemisphere. In addition, the largest
      activation was in the contralateral right cerebellum, as well as the anterior
      vermis. CONCLUSIONS: A language-based TOM task activated distributed brain
      regions that are important for representing mental states of the self and others,
      retrieving memory of personal experiences, and coordinating and monitoring the
      overall performance of the task. The activations in the medial frontal cortex
      replicate findings in previous TOM studies, while the activations in the
      cerebellum reinforce the growing evidence that the cerebellum performs cognitive
      functions in the human brain.

PMID- 14594742
TI  - The serotonin system and spiritual experiences.
AB  - OBJECTIVE: The serotonin system has long been of interest in biological models of
      human personality. The purpose of this positron emission tomography (PET) study
      was to search for relationships between serotonin 5-HT(1A) receptor density and
      personality traits. METHOD: Fifteen normal male subjects, ages 20-45 years, were
      examined with PET and the radioligand [(11)C]WAY100635. Personality traits were
      assessed with the Swedish version of the Temperament and Character Inventory self
      report questionnaire. Binding potential, an index for the density of available 5
      HT(1A) receptors, was calculated for the dorsal raphe nuclei, the hippocampal
      formation, and the neocortex. For each region, correlation coefficients between 5
      HT(1A) receptor binding potential and Temperament and Character Inventory
      personality dimensions were calculated and analyzed in two-tailed tests for
      significance. RESULTS: The authors found that the binding potential correlated
      inversely with scores for self-transcendence, a personality trait covering
      religious behavior and attitudes. No correlations were found for any of the other
      six Temperament and Character Inventory dimensions. The self-transcendence
      dimension consists of three distinct subscales, and further analysis showed that
      the subscale for spiritual acceptance correlated significantly with binding
      potential but not with the other two subscales. CONCLUSIONS: This finding in
      normal male subjects indicated that the serotonin system may serve as a
      biological basis for spiritual experiences. The authors speculated that the
      several-fold variability in 5-HT(1A) receptor density may explain why people vary
      greatly in spiritual zeal.

PMID- 14594743
TI  - Familial and genetic effects on motor coordination, laterality, and reading
      related cognition.
AB  - OBJECTIVE: Recent research has provided evidence for a genetically mediated
      association between language or reading-related cognitive deficits and impaired
      motor coordination. Other studies have identified relationships between
      lateralization of hand skill and cognitive abilities. With a large sample, the
      authors aimed to investigate genetic relationships between measures of reading
      related cognition, hand motor skill, and hand skill lateralization. METHOD: The
      authors applied univariate and bivariate correlation and familiality analyses to
      a range of measures. They also performed genomewide linkage analysis of hand
      motor skill in a subgroup of 195 sibling pairs. RESULTS: Hand motor skill was
      significantly familial (maximum heritability=41%), as were reading-related
      measures. Hand motor skill was weakly but significantly correlated with reading
      related measures, such as nonword reading and irregular word reading. However,
      these correlations were not significantly familial in nature, and the authors did
      not observe linkage of hand motor skill to any chromosomal regions implicated in
      susceptibility to dyslexia. Lateralization of hand skill was not correlated with
      reading or cognitive ability. CONCLUSIONS: The authors confirmed a relationship
      between lower motor ability and poor reading performance. However, the genetic
      effects on motor skill and reading ability appeared to be largely or wholly
      distinct, suggesting that the correlation between these traits may have arisen
      from environmental influences. Finally, the authors found no evidence that
      reading disability and/or low general cognitive ability were associated with
      ambidexterity.

PMID- 14594744
TI  - Elevated risk of tobacco dependence among offspring of mothers who smoked during
      pregnancy: a 30-year prospective study.
AB  - OBJECTIVE: The authors' goal was to investigate whether maternal smoking during
      pregnancy is associated with an increased risk of nicotine dependence among adult
      offspring. METHOD: Prospective data from two samples of offspring in the National
      Collaborative Perinatal Project, a long-term prospective investigation from
      pregnancy through adulthood, were combined (N=1,248). Maternal smoking during
      pregnancy was assessed during each prenatal visit. Offspring smoking behavior and
      lifetime risk of nicotine dependence were obtained by structured interview with
      the Diagnostic Interview Schedule; the mean age of the offspring at the time of
      interview was 29 years. RESULTS: Offspring whose mothers reported smoking a pack
      or more of cigarettes during their pregnancy were significantly more likely to
      meet DSM criteria for lifetime tobacco dependence than offspring of mothers who
      reported that they never smoked during pregnancy. The odds of progressing from
      smoking to nicotine dependence were almost twice as great for offspring whose
      mothers smoked heavily during pregnancy. These significant differences remained
      after adjustments for participants' gender and age and maternal socioeconomic
      status and age at pregnancy. Results were comparable for men and women. The
      findings were specific for tobacco dependence; odds of marijuana dependence were
      not significantly elevated among the offspring of tobacco smokers. CONCLUSIONS:
      Offspring of mothers who smoked a pack or more of cigarettes during pregnancy are
      at elevated risk of developing nicotine dependence but not marijuana dependence
      as adults. Maternal smoking during pregnancy is a risk factor for subsequent
      nicotine dependence among offspring.

PMID- 14594745
TI  - Maternal smoking during pregnancy and attention deficit hyperactivity disorder
      symptoms in offspring.
AB  - OBJECTIVE: The aim of this study was to examine whether smoking during pregnancy
      is associated with symptoms of attention deficit hyperactivity disorder (ADHD) in
      offspring and whether these effects are additional to genetic influences. METHOD:
      Children's ADHD symptoms (parent- and teacher-rated), maternal smoking during
      pregnancy, conduct disorder symptoms, and family adversity were assessed with
      questionnaires for a population-based sample of twins (1,452 twin pairs 5-16
      years of age). RESULTS: Although genetic influences accounted for most of the
      variance in offspring ADHD, maternal smoking during pregnancy was still found to
      show a significant environmentally mediated association. Maternal smoking
      remained a significant influence when other potential confounds were taken into
      account. CONCLUSIONS: Maternal smoking during pregnancy appears to show an
      association with offspring ADHD symptoms that is additional to the effects of
      genes and not attributable to shared rater effects, clinical referral biases, or
      covariation with antisocial behavior.

PMID- 14594746
TI  - An FMRI Stroop task study of ventromedial prefrontal cortical function in
      pathological gamblers.
AB  - OBJECTIVE: Function of the ventromedial prefrontal cortex has been implicated in
      impulse control. The authors used the Stroop paradigm to test attention and
      response inhibition during the presentation of congruent and incongruent stimuli
      in male pathological gamblers and a group of comparison subjects. METHOD: Event
      related functional magnetic resonance imaging was used to examine ventromedial
      prefrontal cortex function during Stroop performance. RESULTS: In response to
      infrequent incongruent stimuli, pathological gamblers demonstrated decreased
      activity in the left ventromedial prefrontal cortex relative to the comparison
      subjects. Both groups demonstrated similar activity changes in multiple brain
      regions, including activation of the dorsal anterior cingulate and dorsolateral
      frontal cortex. CONCLUSIONS: Pathological gamblers share many neural correlates
      of Stroop task performance with healthy subjects but differ in a brain region
      previously implicated in disorders characterized by poor impulse control.

PMID- 14594747
TI  - Olfactory function in mild cognitive impairment and Alzheimer's disease: an
      investigation using psychophysical and electrophysiological techniques.
AB  - OBJECTIVE: To clarify the olfactory deficit hypothesis regarding Alzheimer's
      disease, the authors compared olfactory function in patients with Alzheimer's
      disease, subjects with mild cognitive impairment, and healthy comparison
      subjects. METHOD: Olfactory function of 14 patients with mild Alzheimer's
      disease, eight subjects with mild cognitive impairment, and eight healthy age
      matched comparison subjects was assessed with both psychophysical tests and
      olfactory event-related potentials. RESULTS: Group comparison of the
      psychophysical test results showed a significant main effect of diagnosis for
      odor detection threshold, odor discrimination, and odor identification. These
      results correlated only partially with those obtained from olfactory event
      related potentials. Seven Alzheimer's disease patients and four with mild
      cognitive impairment showed no olfactory event-related potentials, suggesting
      hyposmia, while all comparison subjects had clearly discernible responses.
      Patients with Alzheimer's disease were significantly more likely to be
      nonresponders. In the four Alzheimer's disease patients and four subjects with
      mild cognitive impairment who had clear electrophysiological responses,
      amplitudes and latencies of the various event-related potential components were
      normal, i.e., similar to those of the comparison subjects, although 12 of the 14
      Alzheimer's disease patients and seven of the eight mildly impaired subjects were
      classified as functionally anosmic with psychophysical methods. CONCLUSIONS: The
      electrophysiological results confirm prior findings of olfactory dysfunction in
      patients with Alzheimer's disease and preclinical Alzheimer's disease.
      Investigations of larger study groups with detailed cognitive examination and
      postmortem diagnosis may resolve the intriguing possibility of early diagnosis
      and discrimination of Alzheimer's disease subtypes through chemosensory event
      related potentials in addition to existing biomarkers.

PMID- 14594748
TI  - Randomized, placebo-controlled trial of the effects of donepezil on neuronal
      markers and hippocampal volumes in Alzheimer's disease.
AB  - OBJECTIVE: The authors examined the effect of the acetylcholinesterase inhibitor
      donepezil on magnetic resonance markers of neurodegeneration in Alzheimer's
      disease. METHOD: In this randomized, double-blind, placebo-controlled pilot
      study, 67 patients with mild to moderate Alzheimer's disease received 24 weeks of
      treatment with donepezil (5 mg/day for the first 28 days and 10 mg/day
      thereafter) or placebo. Patients were reevaluated at 6-week intervals to measure
      change from baseline in several outcome measures, including right, left, and
      total hippocampal volumes, measured with magnetic resonance imaging; brain
      concentrations of N-acetylaspartate, measured with proton magnetic resonance
      spectroscopy; and cognition, assessed with the Alzheimer's Disease Assessment
      Scale cognitive subscale. RESULTS: At some interim assessments, mean normalized
      measures of N-acetylaspartate concentration tended to be higher in the donepezil
      treated patients than in the patients who received placebo, but these differences
      were not significant at endpoint. At endpoint, the donepezil-treated patients had
      significantly smaller mean decreases in total and right hippocampal volumes and a
      smaller, nearly significant mean decrease in left hippocampal volume, compared
      with the placebo-treated patients. Mean Alzheimer's Disease Assessment Scale
      cognitive subscale scores were improved after treatment with donepezil, relative
      to placebo, at weeks 6, 12, 18, and 24. CONCLUSIONS: These preliminary results
      suggest that donepezil may have a potentially protective effect in Alzheimer's
      disease. Larger, longer-term confirmatory studies of the medication's effects are
      warranted.

PMID- 14594749
TI  - The utility of mandatory depression screening of dementia patients in nursing
      homes.
AB  - OBJECTIVE: Current methods for enhancing the recognition and treatment of
      depression in nursing home patients have been unsuccessful. This study examines
      the process, outcome, and impact of instituting a mandatory depression screening
      program for depressed dementia patients in nursing homes. METHOD: The
      experimental and comparison groups each consisted of two nursing homes of 519 and
      363 patients, respectively. Two of the experimental group and one of the
      comparison group homes were more traditionally staffed facilities; one of the
      comparison group homes had an enriched staff of psychologists. The Cornell Scale
      for Depression in Dementia was administered to the residents with dementia. In
      the experimental group, the patients who scored > or =5 were referred for
      psychiatric assessment. RESULTS: In the experimental group, 100% of the referred
      dementia patients who met screening criteria for depression were seen by a
      psychiatrist. This resulted in a significant increase in the percentage of
      individuals given antidepressants. This was greater than the percentage of
      patients receiving antidepressants in the "typical" comparison group home but not
      the "staff-enriched" comparison group home. White patients were significantly
      more likely to receive antidepressants; however, screening significantly
      increased the proportion of depressed nonwhites receiving antidepressants. At the
      12-week follow-up, there was a significant difference in scores between patients
      receiving antidepressants in each group. CONCLUSIONS: Mandatory depression
      screening can significantly increase the proportion of depressed dementia
      patients receiving antidepressants, lead to dose adjustments, diminish potential
      ethnic biases in treatment, and affect the depressive symptoms of treated
      individuals.

PMID- 14594750
TI  - The relationship of borderline personality disorder to posttraumatic stress
      disorder and traumatic events.
AB  - OBJECTIVE: The authors examined the relationship of borderline personality
      disorder to posttraumatic stress disorder (PTSD) with respect to the role of
      trauma and its timing. METHOD: The Trauma History Questionnaire and the PTSD
      module of the Structured Clinical Interview for DSM-III-R were administered to
      180 male and female outpatients with a diagnosis of one or more DSM-III-R
      personality disorders. Path analysis was used to evaluate the relationship
      between borderline personality disorder and PTSD. RESULTS: High rates of early
      and lifetime trauma were found for the subject group as a whole. Compared to
      subjects without borderline personality disorder, subjects with borderline
      personality disorder had significantly higher rates of childhood/adolescent
      physical abuse (52.8% versus 34.3%) and were twice as likely to develop PTSD. In
      the path analysis of the relationship between borderline personality disorder and
      PTSD, none of the different types of paths (direct path, indirect paths through
      adulthood traumas, paths sharing the antecedent of childhood abuse) was
      significant. The associations with both trauma and PTSD were not unique to
      borderline personality disorder; paranoid personality disorder subjects had an
      even higher rate of comorbid PTSD than subjects without paranoid personality
      disorder, as well as elevated rates of physical abuse and assault in
      childhood/adolescence and adulthood. CONCLUSIONS: The associations of personality
      disorder with early trauma and PTSD were evident, but modest, in borderline
      personality disorder and were not unique to this type of personality disorder.
      The results do not appear substantial or distinct enough to support singling out
      borderline personality disorder from the other personality disorders as a trauma
      spectrum disorder or variant of PTSD.

PMID- 14594751
TI  - Does patient cognition predict time off from work after life-threatening
      accidents?
AB  - OBJECTIVE: Accidental injuries are frequent and their socioeconomic consequences
      enormous. The present study aimed to identify predictors of the number of days of
      leave taken in a consecutively selected group of accident victims who sustained
      severe, mostly life-threatening physical trauma. METHOD: One hundred patients
      with severe accidental injuries who were referred to a trauma surgeons' intensive
      care unit were followed up for 12 months. The main outcome measure was the number
      of days of leave taken that were attributable to the accident 1 year after the
      trauma. RESULTS: Multiple regression analysis explained 30% of the variance in
      the number of days of leave taken that were attributable to the accident. Factors
      contributing to the predictive model were injury severity, type of accident and,
      most significantly, the patients' subjective self-assessment of accident severity
      and of their abilities to cope with the accident and its job-related
      consequences. Patients who perceived the severity of their accident as relatively
      low and judged their coping abilities as high took a mean 121 days of leave
      compared to 287 days of leave taken by those who perceived the trauma as
      relatively severe and were less optimistic regarding their coping abilities. A
      two-factor analysis of variance showed that patient perceptions of accident
      severity and their appraisal of their coping abilities made independent
      contributions to the predicted amount of leave taken. CONCLUSIONS: In severely
      injured accident victims, leave taken because of the accident depended to a
      considerable degree on the patients' accident-related self-assessment.

PMID- 14594752
TI  - Psychiatric disability among tortured Bhutanese refugees in Nepal.
AB  - OBJECTIVE: Most refugees live in low-income countries. There is a lack of data on
      psychiatric disability among such refugees. The authors compared psychiatric
      disability in tortured and nontortured Bhutanese refugees living in Nepal and
      examined factors associated with psychiatric disability among the tortured
      refugees. METHOD: A cross-sectional survey was conducted among 418 tortured and
      392 nontortured Bhutanese refugees, matched for age and gender. The Composite
      International Diagnostic Interview, version 2.1, and the World Health
      Organization Short Disability Assessment Schedule were used to measure ICD-10
      psychiatric disorders and disability, respectively. RESULTS: Approximately one in
      five tortured and nontortured Bhutanese refugees were found to be disabled.
      Posttraumatic stress disorder, specific phobia, and present physical disease were
      identified as factors associated with disability among the tortured refugees. On
      the other hand, present physical disease, greater age, and generalized anxiety
      disorder were associated with disability among the nontortured group.
      CONCLUSIONS: These findings show that the tortured and nontortured refugees were
      equally likely to be disabled. Different sets of predictors were identified among
      tortured and nontortured refugees, indicating the need for comprehensive
      psychiatric assessment of both tortured and nontortured refugees in clinical
      practice.

PMID- 14594753
TI  - Cross-sectional volumetric analysis of brain atrophy in alcohol dependence:
      effects of drinking history and comorbid substance use disorder.
AB  - OBJECTIVE: The authors assessed whether individual differences in drinking
      history as well as lifetime incidence of comorbid cocaine or marijuana use
      disorder underlie differential patterns of brain atrophy in subjects with alcohol
      dependence. METHOD: Segmented magnetic resonance images were used to compare
      whole brain cerebral gray matter and white matter in 134 male subjects age 30-50
      with alcohol dependence, either alone or with comorbid cocaine or marijuana use
      disorder. RESULTS: Across all subjects, drinking history variables correlated
      negatively with both gray matter and white matter after age was controlled.
      Alcohol-dependent subjects with no comorbid substance use disorder (N=51) showed
      a steeper negative correlation between age and the gray matter/white matter ratio
      than did alcohol-dependent subjects with a comorbid lifetime cocaine use disorder
      diagnosis (N=50). Alcohol-dependent subjects with comorbid cocaine use disorder
      tended to have a steeper negative correlation between age and white matter
      (adjusted for intracranial volume) than did alcohol-dependent subjects with no
      comorbid substance use disorder. After age and the greater estimated cumulative
      alcohol consumption of alcohol-dependent subjects with comorbid cocaine use
      disorder were controlled in a multiple regression analysis, however, comorbid
      cocaine use disorder did not account for any independent variance in any
      volumetric measure. CONCLUSIONS: Brain atrophy among subjects with alcohol
      dependence reflects individual differences in exposure to alcohol, and the data
      provide mixed evidence that comorbid cocaine use disorder may exacerbate white
      matter atrophy in alcoholism.

PMID- 14594754
TI  - Cognitive behavior therapy in the posthospitalization treatment of anorexia
      nervosa.
AB  - OBJECTIVE: This study provides what the authors believe is the first empirical
      evaluation of cognitive behavior therapy as a posthospitalization treatment for
      anorexia nervosa in adults. METHOD: After hospitalization, 33 patients with DSM
      IV anorexia nervosa were randomly assigned to 1 year of outpatient cognitive
      behavior therapy or nutritional counseling. RESULTS: The group receiving
      nutritional counseling relapsed significantly earlier and at a higher rate than
      the group receiving cognitive behavior therapy (53% versus 22%). The overall
      treatment failure rate (relapse and dropping out combined) was significantly
      lower for cognitive behavior therapy (22%) than for nutritional counseling (73%).
      The criteria for "good outcome" were met by significantly more of the patients
      receiving cognitive behavior therapy (44%) than nutritional counseling (7%).
      CONCLUSIONS: Cognitive behavior therapy was significantly more effective than
      nutritional counseling in improving outcome and preventing relapse. To the
      authors' knowledge, these data provide the first empirical documentation of the
      efficacy of any psychotherapy, and cognitive behavior therapy in particular, in
      posthospitalization care and relapse prevention of adult anorexia nervosa.

PMID- 14594756
TI  - Association of depression duration with reduction of global cerebral gray matter
      volume in female patients with recurrent major depressive disorder.
AB  - OBJECTIVE: The authors investigated the relationship between depression duration
      and cerebral gray matter volume in female patients with recurrent major
      depressive disorder. METHOD: Magnetic resonance imaging was used to measure
      intracranial and total brain volumes as well as gray matter and white matter
      volumes of the cerebrum; frontal, temporal, parietal, and occipital lobes;
      cerebellum; and the lateral and third ventricles in 23 female patients with DSM
      IV major depression. RESULTS: Correlation and regression analyses showed a
      significant relationship between total illness duration and cerebral gray matter
      (including cortical lobe) volume after correction for intracranial volume and
      age. CONCLUSIONS: Depressive states may lead to changes in global cerebral gray
      matter volume.

PMID- 14594755
TI  - Unipolar mania over the course of a 20-year follow-up study.
AB  - OBJECTIVE: Using data from a longitudinal study of the mood disorders, the
      investigators address the phenomenon of unipolar mania. METHOD: Subjects
      diagnosed as having Research Diagnostic Criteria mania at intake into the study
      were prospectively followed for up to 20 years. RESULTS: Twenty-seven subjects
      had the diagnosis of unipolar mania at the time they entered the study and had no
      history of major depression before enrolling in the study. Seven of these
      subjects did not suffer any episodes of major depression during the 15- to 20
      year follow-up. CONCLUSIONS: These data support the diagnostic validity of
      unipolar mania.

PMID- 14594757
TI  - A preliminary study of left frontal region error negativity and symptom
      improvement in geriatric depression.
AB  - OBJECTIVE: This study tested the hypothesis that frontal error negative wave
      amplitude on EEG during Stroop test activation predict change in depressive
      symptoms in depressed elders. METHOD: Twenty-two older patients with major
      depression received controlled treatment with citalopram at a target dose of 40
      mg/day for 6 weeks. Paramedian error negative waves were recorded during Stroop
      activation before treatment. RESULTS: Nine subjects who remained symptomatic had
      larger left frontal error negative waves than the subjects who achieved
      remission. Left frontal error negative waves were correlated with percent change
      of depressive symptoms from baseline. Other paramedian error negative waves did
      not distinguish remitted from unremitted subjects. Left frontal error negative
      waves were negatively correlated with Mattis Dementia Rating Scale scores for
      initiation/perseveration; these scores were lower in unremitted than remitted
      patients. CONCLUSIONS: Increased left frontal error negative waves are associated
      with limited or slow change in depressive symptoms in elders receiving
      citalopram.

PMID- 14594758
TI  - Perception of complex sounds: abnormal pattern of cortical activation in autism.
AB  - OBJECTIVE: Bilateral temporal hypoperfusion at rest was recently described in
      autism. In normal adults, these regions are activated by listening to speech-like
      sounds. To investigate auditory cortical processing in autism, the authors
      performed a positron emission tomography activation study. METHOD: Regional
      cerebral blood flow was measured in five autistic adults and eight comparison
      subjects during rest and while listening to speech-like sounds. RESULTS: Similar
      to the comparison subjects, autistic patients showed a bilateral activation of
      the superior temporal gyrus. However, an abnormal pattern of hemispheric
      activation was observed in the autistic group. The volume of activation was
      larger on the right side in the autistic patients, whereas the reverse pattern
      was found in the comparison group. The direct comparison between the two groups
      showed that the right middle frontal gyrus exhibited significantly greater
      activation in the autistic group. Conversely, the left temporal areas exhibited
      less activation in autistic patients. CONCLUSIONS: These findings suggest that
      abnormal auditory cortical processing is implicated in the language impairments
      and the inadequate response to sounds typically seen in autism.

PMID- 14594759
TI  - A prospective study of childhood neurocognitive functioning in schizophrenic
      patients and their siblings.
AB  - OBJECTIVE: This study evaluated childhood cognitive functioning in individuals
      who later developed schizophrenia and in their unaffected siblings. METHOD:
      Through the National Collaborative Perinatal Project, seven subtests of the
      Wechsler Intelligence Scale for Children were administered at age 7 to 32
      individuals who developed schizophrenia in adulthood, 25 of their
      nonschizophrenic siblings, and 201 demographically similar nonpsychiatric
      comparison subjects. Mixed model analysis was used to examine between-group
      differences in standardized scores on the subtests. RESULTS: The probands and
      unaffected siblings had lower scores for picture arrangement, vocabulary, and
      coding than the comparison subjects but differed from each other only on the
      coding subtest. CONCLUSIONS: Children who later developed schizophrenia and their
      siblings showed similar patterns of deficits involving spatial reasoning, verbal
      knowledge, perceptual-motor speed, and speeded processes of working memory.
      However, the probands exhibited more severe deficits in perceptual-motor speed
      and speeded processes of working memory than their unaffected siblings.

PMID- 14594772
TI  - Copyright protection and open access.

PMID- 14594760
TI  - Early prediction of antipsychotic response in schizophrenia.
AB  - OBJECTIVE: The authors' goal was to examine the predictive value of early symptom
      changes indicating response to antipsychotic medication in schizophrenia. METHOD:
      One hundred thirty-one acutely ill patients with schizophrenia received 4 weeks
      of fluphenazine treatment. Brief Psychiatric Rating Scale (BPRS) ratings were
      obtained at baseline and weekly. The authors examined the relationship between
      changes in BPRS total score and each factor score following 1 week of treatment
      and ultimate response status, defined as a reduction of 20% or more in total BPRS
      score. RESULTS: None of the patients who [corrected] displayed an improvement of
      less than 20% in total [corrected] BPRS score and only 5% [corrected] of the
      [corrected] patients who displayed a reduction of less than 20% in BPRS thought
      disturbance [corrected] score after 4 weeks of treatment had been classified as
      responders at 1 week (i.e., 100% and 95% specificity) [corrected] CONCLUSIONS:
      These data suggest that patients with minimal improvement in positive symptoms
      during the first week of treatment with a typical antipsychotic are unlikely to
      respond to a 4-week trial. These data require confirmation and extension to
      studies with second-generation antipsychotics.

PMID- 14594761
TI  - Olanzapine effects on auditory sensory gating in schizophrenia.
AB  - OBJECTIVE: New-generation antipsychotics have been proposed to normalize the P50
      sensory gating index in patients with schizophrenia. In the context of a double
      blind comparison of olanzapine and haloperidol, the authors examined the effect
      of olanzapine on P50 suppression. METHOD: P50 measurements were obtained at
      baseline while patients were being treated with fluphenazine and after 12 weeks
      of double-blind treatment with either olanzapine (N=12) or haloperidol (N=12).
      RESULTS: There were no treatment group differences in P50 amplitude, latency, or
      sensory gating ratio. CONCLUSIONS: These results suggest that there is not a
      significant differential effect of olanzapine and haloperidol on the P50 sensory
      gating index in schizophrenia.

PMID- 14594773
TI  - Waist circumference: a simple, inexpensive, and reliable tool that should be
      included as part of physical examinations in the doctor's office.

PMID- 14594774
TI  - On the hazards of seeing the world through intervention-colored glasses.

PMID- 14594775
TI  - Protein and energy provision in critical illness.
AB  - It has recently been recommended that parenterally fed, critically ill patients
      should receive considerably less energy than the 36 kcal.kg(-1).d(-1) customarily
      received in earlier years and that mixed amino acid infusions not exceed 1.5
      g.kg(-1).d(-1). The implications of these recommendations should be considered
      carefully, especially for patients with low body weight. Any sizeable reduction
      in energy provision will lead to negative energy balance in at least some
      patients, and negative energy balance is known to increase protein requirements.
      The optimal rate of amino acid delivery for underfed, critically ill patients is
      not well defined and could well exceed 1.5 g.kg(-1).d(-1). In addition, there are
      good reasons to suspect that the safe protein requirement of severely
      underweight, critically ill patients is >1.5 g.kg(-1).d(-1), even when adequate
      energy is provided.

PMID- 14594776
TI  - Long-latency deficiency disease: insights from calcium and vitamin D.
AB  - Nutrient intake recommendations and national nutritional policies have focused
      primarily on prevention of short-latency deficiency diseases. Most nutrient
      intake recommendations today are based on prevention of the index disease only.
      However, inadequate intakes of many nutrients are now recognized as contributing
      to several of the major chronic diseases that affect the populations of the
      industrialized nations. Often taking many years to manifest themselves, these
      disease outcomes should be thought of as long-latency deficiency diseases.
      Sometimes they come about by the same pathophysiologic mechanism that produces
      the index disease, but sometimes the mechanisms are completely different. Well
      documented examples of both short- and long-latency deficiency states involving
      calcium and vitamin D are described briefly. Then, the insights derived from
      these nutrients are tentatively applied to folic acid. Discerning the full role
      of nutrition in long-latency, multifactorial disorders is probably the principal
      challenge facing nutritional science today. The first component of this challenge
      is to recognize that inadequate intakes of specific nutrients may produce more
      than one disease, may produce diseases by more than one mechanism, and may
      require several years for the consequent morbidity to be sufficiently evident to
      be clinically recognizable as "disease." Because the intakes required to prevent
      many of the long-latency disorders are higher than those required to prevent the
      respective index diseases, recommendations based solely on preventing the index
      diseases are no longer biologically defensible.

PMID- 14594778
TI  - Metabolic risks identified by the combination of enlarged waist and elevated
      triacylglycerol concentration.
AB  - BACKGROUND: Abdominal fat and circulating triacylglycerols increase with age,
      which indicates lipid overaccumulation. Enlarged waist (EW) with elevated
      triacylglycerols (ET) could identify adults at metabolic risk. OBJECTIVE: Using
      thresholds for EW and ET observed among the youngest adults, we estimated for all
      adults the prevalence of combined EW and ET (EWET) and described the metabolic
      risks associated with EWET. DESIGN: In a cross-sectional, weighted sample of 9183
      adults, we used two-dimensional displays to provide thresholds for EW (men: > or
      = 95 cm; women: > or = 88 cm) and fasting ET (> or = 1.45 mmol/L) and estimated
      the characteristics of EWET among adults of all ages. RESULTS: The population
      prevalence of EWET in 18-24-y-olds was 6%; it rose with age until age 55-74 y
      (prevalence: 43%) and then was lower among the elderly. Persons with EWET were
      more likely (P < 0.0001) to have adverse mean (+/- SEE) concentrations of risk
      variables in adjusted analyses (fasting insulin: 43 +/- 3 pmol/L; HDL
      cholesterol: -0.27 +/- 0.02 mmol/L; apolipoprotein B: 0.20 +/- 0.01 g/L; fasting
      glucose: 0.71 +/- 0.07 mmol/L; uric acid: 50 +/- 2 micromol/L) and to have
      diabetes (relative risk: 3.2) than were persons without EWET. Compared with a
      similar-size subpopulation with high body mass index, persons with EWET were
      older and had more dyslipidemia, hyperglycemia, and hyperuricemia. Compared with
      "metabolic syndrome," EWET identified more persons who were younger and had
      greater LDL-cholesterol and apolipoprotein B concentrations. Compared with
      "prediabetes," EWET identified more persons with hyperinsulinemia, dyslipidemia,
      and hyperuricemia. CONCLUSIONS: EWET identifies a syndrome of lipid
      overaccumulation associated with metabolic risk and accelerated mortality after
      middle age. Prospective studies should evaluate this simple indicator.

PMID- 14594777
TI  - Relation between changes in intakes of dietary fiber and grain products and
      changes in weight and development of obesity among middle-aged women.
AB  - BACKGROUND: Although increased consumption of dietary fiber and grain products is
      widely recommended to maintain healthy body weight, little is known about the
      relation of whole grains to body weight and long-term weight changes. OBJECTIVE:
      We examined the associations between the intakes of dietary fiber and whole- or
      refined-grain products and weight gain over time. DESIGN: In a prospective cohort
      study, 74,091 US female nurses, aged 38-63 y in 1984 and free of known
      cardiovascular disease, cancer, and diabetes at baseline, were followed from 1984
      to 1996; their dietary habits were assessed in 1984, 1986, 1990, and 1994 with
      validated food-frequency questionnaires. Using multiple models to adjust for
      covariates, we calculated average weight, body mass index (BMI; in kg/m(2)), long
      term weight changes, and the odds ratio of developing obesity (BMI > or = 30)
      according to change in dietary intake. RESULTS: Women who consumed more whole
      grains consistently weighed less than did women who consumed less whole grains (P
      for trend < 0.0001). Over 12 y, those with the greatest increase in intake of
      dietary fiber gained an average of 1.52 kg less than did those with the smallest
      increase in intake of dietary fiber (P for trend < 0.0001) independent of body
      weight at baseline, age, and changes in covariate status. Women in the highest
      quintile of dietary fiber intake had a 49% lower risk of major weight gain than
      did women in the highest quintile (OR = 0.51; 95% CI: 0.39, 0.67; P < 0.0001 for
      trend). CONCLUSION: Weight gain was inversely associated with the intake of high
      fiber, whole-grain foods but positively related to the intake of refined-grain
      foods, which indicated the importance of distinguishing whole-grain products from
      refined-grain products to aid in weight control.

PMID- 14594779
TI  - Dietary and antismoking advice and ischemic heart disease mortality in men with
      normal or high fasting triacylglycerol concentrations: a 23-y follow-up study.
AB  - BACKGROUND: In the Oslo Diet and Antismoking Trial, 1232 high-risk men aged 40-49
      y were randomly assigned to either a lifestyle intervention group or a control
      group for 5 y. The study showed a significant reduction in ischemic heart disease
      (IHD) events in the intervention group. OBJECTIVE: Our objective was to examine
      this cohort 23 y after the start of the trial. DESIGN: We examined the effect of
      group assignment on IHD mortality in subjects with a normal (below the median;
      range: 0.69-2.00 mmol/L; n = 615) or a high (at or above the median; range: 2.01
      13.80 mmol/L; n = 617) fasting triacylglycerol concentration in 1972-1973 (at
      inclusion into the study). We recorded vital status on 31 December 1996 and
      ascertained causes of death by linkage to Statistics Norway. RESULTS: In the men
      with a high triacylglycerol concentration, IHD death occurred in 25 (8.13%)
      subjects in the intervention group and in 44 (14.2%) subjects in the control
      group (relative risk: 0.57; 95% CI: 0.36, 0.91; P = 0.02). An adjusted Cox
      proportional hazards model yielded a hazard ratio of 0.56 (95% CI: 0.34, 0.93; P
      = 0.027). In the men with a normal triacylglycerol concentration, the
      intervention had no detectable effect on IHD mortality (adjusted hazard ratio:
      1.10; 95% CI: 0.66, 1.83; P = 0.7). CONCLUSIONS: These data suggest that advice
      to change diet and smoking habits reduced the relative risk of IHD mortality
      after 23 y in men with high triacylglycerol concentrations. Men with normal
      triacylglycerol concentrations did not appear to achieve this long-term benefit
      of lifestyle intervention.

PMID- 14594780
TI  - Reproducibility and validity of the Diet Quality Index Revised as assessed by use
      of a food-frequency questionnaire.
AB  - BACKGROUND: The Diet Quality Index Revised (DQI-R) is a dietary assessment
      instrument based on 10 dietary recommendations reflecting dietary guidelines and
      policy in the United States. OBJECTIVE: The objective of this study was to assess
      the reproducibility and validity of the DQI-R as measured by use of food
      frequency questionnaires (FFQs). DESIGN: Diet was assessed separately by two FFQs
      at a 1-y interval and by two 1-wk diet records. DQI-R scores were computed from
      each method. Venous blood specimens were collected for measurement of dietary
      biomarkers. Participants (n = 127) were men aged 40-75 y in a validation study of
      the Health Professionals Follow-up Study. RESULTS: Mean DQI-R scores were 69.5
      for FFQ-1, 67.2 for FFQ-2, and 62.0 for the diet records out of a possible score
      of 100. The reproducibility correlation for the 2 FFQ scores was 0.72.
      Correlations between scores for each of the 2 FFQs and diet records were 0.66
      (FFQ-1) and 0.72 (FFQ-2). DQI-R scores from FFQ-2 were directly correlated with
      plasma biochemical measurements of alpha-carotene (r = 0.43, P < 0.0005), beta
      carotene (r = 0.35, P < 0.005), lutein (r = 0.31, P <0.005), and alpha-tocopherol
      (r = 0.25, P < 0.05) and were inversely correlated with plasma total cholesterol
      (r = -0.22, P < 0.05). CONCLUSIONS: These data indicate reasonable
      reproducibility and validity of the DQI-R as assessed by an FFQ. Future studies
      are needed to examine whether this index and other instruments of diet quality
      can reliably predict disease outcomes.

PMID- 14594781
TI  - Effects of 16 mo of verified, supervised aerobic exercise on macronutrient intake
      in overweight men and women: the Midwest Exercise Trial.
AB  - BACKGROUND: It is commonly believed that moderate aerobic exercise leads to
      changes in diet composition, specifically, an increase in carbohydrate intake at
      the expense of fat intake. OBJECTIVE: The goal was to determine the effects of a
      supervised, long-term program of exercise on the macronutrient intake of
      previously sedentary, overweight and moderately obese men and women. DESIGN:
      Participants (n = 74) were recruited from the university and surrounding
      communities and were randomly assigned to the exercise or control group. Exercise
      of moderate intensity was performed for 45 min/d, 5 d/wk, under supervision. Diet
      intake was ad libitum and was measured for energy and macronutrient composition
      at baseline and at 5 other occasions across the 16-mo study by use of weighing
      and measuring techniques. Each measurement consisted of a 2-wk period of direct
      measurement in the university cafeteria. Food consumption outside the cafeteria
      during the 2-wk periods (ie, snacks) was measured by multiple-pass 24-h dietary
      recall procedures. RESULTS: There were no significant differences for men or
      women between the exercise and control groups from baseline to 16 mo in fat,
      carbohydrate, or protein intake expressed as grams or as percentages of total
      energy intake. CONCLUSION: Sixteen months of exercise of moderate intensity does
      not measurably alter the macronutrient intake of young adults.

PMID- 14594782
TI  - Structural differences between rye and wheat breads but not total fiber content
      may explain the lower postprandial insulin response to rye bread.
AB  - BACKGROUND: Rye bread has a beneficial effect on the postprandial insulin
      response in healthy subjects. The role of rye fiber in insulin and glucose
      metabolism is not known. OBJECTIVE: The aim of the study was to determine the
      effect of the content of rye fiber in rye breads on postprandial insulin and
      glucose responses. DESIGN: Nineteen healthy postmenopausal women aged 61 +/- 1 y,
      with a body mass index (in kg/m(2)) of 26.0 +/- 0.6, and with normal glucose
      tolerance participated in the study. The test products were refined wheat bread
      (control), endosperm rye bread, traditional rye bread, and high-fiber rye bread;
      each bread provided 50 g available carbohydrate and was served with breakfast.
      Plasma glucose, insulin, glucose-dependent insulinotropic polypeptide, glucagon
      like peptide 1, and serum C-peptide were measured in fasting and 8 postprandial
      blood samples. In vitro starch hydrolysis and the microscopic structure of the
      breads were also determined. RESULTS: Postprandial insulin, glucose-dependent
      insulinotropic polypeptide, and C-peptide responses to the rye breads were
      significantly lower than the response to the control; no significant differences
      in insulin and C-peptide responses to the rye breads were found. Glucose and
      glucagon-like peptide 1 responses to the rye breads were not significantly
      different from those to the control, except at 150 and 180 min. In vitro starch
      hydrolysis was slower in all rye breads than in the control, and the structure of
      continuous matrix and starch granules differed between the rye and control
      breads. CONCLUSION: Total fiber content does not explain the lower postprandial
      insulin response to rye bread than to wheat bread, but structural differences
      between rye and wheat breads might.

PMID- 14594783
TI  - Whole-grain intake and insulin sensitivity: the Insulin Resistance
      Atherosclerosis Study.
AB  - BACKGROUND: Increased intake of whole-grain foods has been related to a reduced
      risk of developing diabetes and heart disease. One underlying pathway for this
      relation may be increased insulin sensitivity. OBJECTIVE: We assessed the
      relation between dietary intake of whole grain-containing foods and insulin
      sensitivity (S(I)). DESIGN: We evaluated data from the Insulin Resistance
      Atherosclerosis Study (IRAS Exam I, 1992-1994). Usual dietary intakes in 978
      middle-aged adults with normal (67%) or impaired (33%) glucose tolerance were
      ascertained by using an interviewer-administered, validated food-frequency
      questionnaire. Whole-grain intake (servings per day) was derived from dark breads
      and high-fiber and cooked cereals. S(I) was assessed by minimal model analyses of
      the frequently sampled intravenous-glucose-tolerance test. Fasting insulin was
      measured by using a radioimmunoassay. We modeled the relation of whole-grain
      intake to log(S(I) + 1) and to log(insulin) by using multivariable linear
      regression. RESULTS: On average, IRAS participants consumed 0.8 servings of whole
      grains/d. Whole-grain intake was significantly associated with S(I) (beta =
      0.082, P = 0.0005) and insulin (beta = -0.0646, P = 0.019) after adjustment for
      demographics, total energy intake and expenditure, smoking, and family history of
      diabetes. The addition of body mass index and waist circumference attenuated but
      did not explain the association with S(I). The addition of fiber and magnesium
      resulted in a nonsignificant association that is consistent with the hypothesis
      that these constituents account for some of the effect of whole grains on S(I).
      CONCLUSION: Higher intakes of whole grains were associated with increases in
      insulin sensitivity.

PMID- 14594784
TI  - Neural tube defects associated with maternal periconceptional dietary intake of
      simple sugars and glycemic index.
AB  - BACKGROUND: Maternal diabetes, prepregnancy obesity, hyperinsulinemia, and
      intakes of sweets have been associated with increased risks of neural tube
      defects (NTDs). The interdependence of these factors suggests a common
      pathogenesis via altered glycemic control and insulin demand. OBJECTIVE: We
      investigated whether maternal periconceptional dietary intakes of sucrose,
      glucose, fructose, and foods with higher glycemic index values influence the risk
      of having NTD-affected pregnancies. DESIGN: In a population-based case-control
      study, all hospitals in 55 of the 58 counties in California participated. In
      person interviews were conducted with the mothers of 454 NTD cases (including
      fetuses and infants who were electively terminated, stillborn, or born alive) and
      with the mothers of 462 nonmalformed controls within an average of 5 mo from the
      term delivery date. The risk of having an NTD-affected pregnancy was the main
      outcome measure. RESULTS: Risks of having an NTD-affected pregnancy were not
      substantially elevated in relation to periconceptional intakes of glucose or
      fructose. Elevated risks of approximately 2-fold were observed for higher intakes
      of sucrose and foods with higher glycemic index values. Elevated risks were
      observed for high sucrose intake irrespective of whether adjustment was made for
      other covariates such as maternal folic acid intake. For higher glycemic index
      values, adjusted elevated risks of > or = 4-fold were observed in women whose
      body mass index (in kg/m(2)) was > 29. CONCLUSION: Our observed associations
      support observations that potential problems in glucose control are associated
      with NTD risk even among nondiabetic women.

PMID- 14594786
TI  - Spread supplemented with moderate doses of vitamin E and carotenoids reduces
      lipid peroxidation in healthy, nonsmoking adults.
AB  - BACKGROUND: High doses of vitamin E have been shown to decrease lipid
      peroxidation in persons under oxidative stress. At present, the data are
      insufficient to predict whether lower doses offer the same benefit in healthy
      persons. OBJECTIVE: We studied the effect of moderate doses of a combination of
      vitamin E and carotenoids, incorporated into a food product, on markers of
      antioxidant status and lipid peroxidation in healthy persons. DESIGN: One hundred
      five healthy adults were randomly, evenly assigned in this double-blind, placebo
      controlled, parallel, 11-wk intervention study. After a 2-wk stabilization period
      during which the subjects consumed a commercial unfortified spread, the subjects
      consumed 25 g/d of spread containing 43 mg alpha-tocopherol equivalents (alpha
      TE; 2-3 fold the US dietary reference intake) and 0.45 mg carotenoids (spread A),
      111 mg alpha-TE and 1.24 mg carotenoids (spread B), or 1.3 mg RRR-alpha
      tocopherol without carotenoids (spread C). RESULTS: In subjects consuming spread
      A, plasma alpha-tocopherol concentrations increased 31% to 32 micromol/L, with
      small but significant increases in concentrations of alpha-carotene and lutein.
      This resulted in LDL with significantly higher total antioxidant capacity (17%)
      and an increased resistance to oxidation, as determined by lag time (18%). These
      improvements were dose dependent: larger increases in these variables were
      observed in subjects consuming spread B. Furthermore, consumption of spread B
      significantly reduced concentrations of the plasma lipid peroxidation biomarker
      F(2 alpha)-isoprostane (15%). CONCLUSION: The consumption of food products
      containing moderate amounts of vitamin E and carotenoids can lead to measurable
      and significant improvements in antioxidant status and biomarkers of oxidative
      stress in healthy persons.

PMID- 14594785
TI  - Total body protein: a new cellular level mass and distribution prediction model.
AB  - BACKGROUND: Protein is an important body component, and the presently accepted
      criterion method for estimating total body protein (TBPro) mass--in vivo neutron
      activation (IVNA) analysis--is unavailable to most investigators and is
      associated with moderate radiation exposure. OBJECTIVE: The objective was to
      derive a theoretical cellular level TBPro mass and distribution model formulated
      on measured total body potassium, total body water, and bone mineral and to
      evaluate the new model with the IVNA method as the criterion. DESIGN: The new
      model was developed on the basis of a combination of theoretical equations and
      empirically derived coefficients. TBPro mass estimates with the new model were
      evaluated in healthy women (n = 183) and men (n = 24) and in men with AIDS (n =
      84). Total body nitrogen was measured by IVNA, total body potassium by whole-body
      (40)K counting, total body water by tritium dilution, and bone mineral by dual
      energy X-ray absorptiometry. RESULTS: The group mean (+/- SD) TBPro mass
      estimates in healthy women and men and men with AIDS (8.2 +/- 0.9, 11.0 +/- 1.8,
      and 10.5 +/- 1.1 kg, respectively) with the new model were similar to IVNA
      criterion estimates (8.9 +/- 0.9, 11.1 +/- 1.6, and 10.9 +/- 1.2 kg,
      respectively). TBPro mass estimates with the new model correlated highly with the
      IVNA estimates in all subjects combined (r = 0.92, P < 0.001). The new model
      suggests that the composite TBPro mass within each group consists mainly of
      cellular protein (75-79%) and, to a lesser extent, protein in extracellular
      solids (19-23%) and extracellular fluid (approximately 2%). CONCLUSION: The new
      model provides a non-IVNA approach for estimating protein mass and distribution
      in vivo.

PMID- 14594787
TI  - Calcium supplementation provides an extended window of opportunity for bone mass
      accretion after menarche.
AB  - BACKGROUND: High calcium intakes during adolescence may increase bone
      acquisition. The magnitude of the effect of dietary calcium supplementation and
      the timing of its administration to achieve significant effects on bone health
      are still incompletely defined. OBJECTIVE: The objective of this study was to
      assess the effect of calcium supplementation on bone mass accretion in
      postmenarcheal adolescent girls with low calcium intakes. DESIGN: A double-blind,
      placebo-controlled calcium supplementation study was implemented. One hundred
      girls with a mean (+/- SD) age of 14 +/- 0.5 y with habitual calcium intakes <
      800 mg/d completed a 12-mo protocol. The treatment group received a daily
      supplement containing 1000 mg elemental calcium. Bone mineral density (BMD) and
      bone mineral content (BMC) of the total body, lumbar spine, and femoral neck were
      determined at inclusion, 6 mo, and 12 mo. Also measured were serum concentrations
      of biochemical markers of bone turnover (osteocalcin and deoxypyridinoline),
      parathyroid hormone, and vitamin D. RESULTS: The calcium-supplemented group had
      greater accretion of total-body BMD and lumbar spine BMD but not BMC than did the
      control group. Calcium supplementation appeared selectively beneficial for girls
      who were 2 y postmenarcheal. Calcium supplementation significantly decreased bone
      turnover and decreased serum parathyroid hormone concentrations. CONCLUSION:
      Calcium supplementation of postmenarcheal girls with low calcium intakes enhances
      bone mineral acquisition, especially in girls > 2 y past the onset of menarche.

PMID- 14594788
TI  - Antioxidant vitamins and mortality in older persons: findings from the nutrition
      add-on study to the Medical Research Council Trial of Assessment and Management
      of Older People in the Community.
AB  - BACKGROUND: Older persons are at risk of both poor nutrition and increased
      oxidative stress. Plasma ascorbate concentrations fall with increasing age, and
      concentrations of other antioxidants may also be reduced. OBJECTIVE: The goal was
      to examine the association between antioxidants and mortality in older persons.
      DESIGN: We randomly selected persons aged 75-84 y from the lists of 51 British
      family practitioners taking part in a randomized trial of assessment of older
      persons. A total of 1214 participants provided a blood sample and were
      interviewed about their usual diet with the use of a food-frequency
      questionnaire. Statistical analyses were based on deaths after a median of 4.4 y
      of follow-up, and hazard ratios were estimated for quintiles of dietary or blood
      antioxidants. RESULTS: We found strong inverse trends for blood ascorbate
      concentrations with all-cause and cardiovascular disease mortality, which were
      only marginally reduced after adjustment for confounders or supplement use. Those
      in the lowest fifth (< 17 micromol/L) had the highest mortality, whereas those in
      the highest fifth (> 66 micromol/L) had a mortality risk nearly half that (hazard
      ratio = 0.54; 95% CI: 0.34, 0.84). Similar results were found after the exclusion
      of those subjects with cardiovascular disease or cancer at baseline (hazard ratio
      = 0.51; 0.28, 0.93). In fully adjusted models, there was no evidence for an
      influence of alpha-tocopherol, beta-carotene, or retinol on total mortality.
      Dietary antioxidants measured by the food-frequency questionnaire were not
      associated with all-cause or cardiovascular disease mortality. CONCLUSION: Low
      blood vitamin C concentrations in the older British population are strongly
      predictive of mortality.

PMID- 14594789
TI  - Zinc intake of US preschool children exceeds new dietary reference intakes.
AB  - BACKGROUND: The recent dietary reference intakes publication provides updated
      information on the physiologic and dietary requirements for zinc and proposes new
      tolerable upper intake levels. OBJECTIVE: We analyzed dietary intake data of US
      preschool children to determine the prevalence of inadequate and excessive
      intakes of zinc. DESIGN: Diets of 7474 nonbreastfeeding preschool children in the
      Continuing Survey of Food Intakes by Individuals (1994-1996 and 1998) were
      analyzed for the intakes of zinc and other dietary components, and factors
      associated with zinc intake were examined. RESULTS: The mean intakes of zinc by
      children aged < 1 y, 1-3 y, and 4-5 y were 6.6, 7.6, and 9.1 mg/d, respectively.
      Less than 1% of children had usual zinc intakes below the adequate intake or
      estimated average requirement. The percentages of children with intakes exceeding
      the tolerable upper intake level were 92% (0-6 mo), 86% (7-12 mo), 51% (1-3 y),
      and 3% (4-5 y). Controlling for age and energy intake, zinc intake was greater in
      1998 than in 1994 (P < 0.0001) and was positively associated with participation
      in the Women, Infants, and Children Program (P < 0.001) and with the lowest
      income category (P < 0.001). CONCLUSIONS: Preschool children in the United States
      have dietary zinc intakes that exceed the new dietary reference intakes. Zinc
      intakes increased during the 4 y of the study. The present level of intake does
      not seem to pose a health problem, but if zinc intake continues to increase
      because of the greater availability of zinc-fortified foods in the US food
      supply, the amount of zinc consumed by children may become excessive.

PMID- 14594790
TI  - Iron supplements inhibit zinc but not copper absorption in vivo in ileostomy
      subjects.
AB  - BACKGROUND: Iron supplements may inhibit intestinal zinc and copper uptake
      because these elements may compete for binding to a transporter molecule
      (divalent metal transporter 1) that is located on the apical side of the small
      intestinal epithelium. OBJECTIVE: We quantified the interaction between different
      amounts of administered iron and the absorption of zinc and copper in humans.
      DESIGN: Eleven subjects with an ileostomy [mean (+/- SD) age: 55 +/- 9 y]
      ingested a stable-isotope-labeled zinc and copper solution containing 12 mg Zn
      ((66)Zn and (67)Zn) and 3 mg Cu ((65)Cu) in the presence of 0, 100, or 400 mg Fe
      as ferrous gluconate on 3 respective test days. Subsequently, 1 mg (70)Zn was
      injected intravenously. Subjects collected ileostomy effluent and urine for 24 h
      and 7 d, respectively. Zinc status and true zinc absorption were calculated from
      the urinary excretion of the zinc isotopes. Apparent copper absorption was
      calculated from ileostomy effluent excretion of the orally administered copper
      isotopes. RESULTS: Zinc status did not differ significantly between the 3 iron
      doses. Mean (+/- SEM) zinc absorption was significantly higher in the absence of
      iron than with the concomitant ingestion of 100 or 400 mg Fe (44 +/- 22% compared
      with 26 +/- 14% and 23 +/- 6%, respectively; P < 0.05), whereas zinc absorption
      did not differ significantly between the 100- and 400-mg Fe doses. Apparent
      copper absorption was 48 +/- 14%, 54 +/- 26%, and 53 +/- 7% in the presence of 0,
      100, and 400 mg Fe, respectively, and did not differ significantly between the 3
      iron doses. CONCLUSION: Oral iron therapy may impair zinc absorption and thus
      zinc status in a dose-independent fashion but does not affect copper absorption.

PMID- 14594791
TI  - Brain ganglioside and glycoprotein sialic acid in breastfed compared with formula
      fed infants.
AB  - BACKGROUND: The concentration of sialic acid in brain gangliosides and
      glycoproteins has been linked to learning ability in animal studies. Human milk
      is a rich source of sialic acid-containing oligosaccharides and is a potential
      source of exogenous sialic acid. OBJECTIVE: The aim of the study was to compare
      the sialic acid concentration in the brain frontal cortex of breastfed and
      formula-fed infants. DESIGN: Twenty-five samples of frontal cortex derived from
      infants who died of sudden infant death syndrome were analyzed. Twelve infants
      were breastfed, 10 infants were formula-fed, and 1 infant was mixed-fed; the
      feeding status of the remaining 2 infants was unknown. Ganglioside-bound and
      protein-bound sialic acid were determined by HPLC. Ganglioside ceramide fatty
      acids were also analyzed to determine the relation between sialic acid and long
      chain polyunsaturated fatty acids. RESULTS: After adjustment for sex with age at
      death as a covariate, ganglioside-bound and protein-bound sialic acid
      concentrations were 32% and 22% higher, respectively, in the frontal cortex gray
      matter of breastfed infants than in that of formula-fed infants (P < 0.01).
      Protein-bound sialic acid increased with age in both groups (P = 0.02). In
      breastfed but not in formula-fed infants, ganglioside-bound sialic acid
      correlated significantly with ganglioside ceramide docosahexaenoic acid and total
      n-3 fatty acids. CONCLUSIONS: Higher brain ganglioside and glycoprotein sialic
      acid concentrations in infants fed human milk suggests increased synaptogenesis
      and differences in neurodevelopment.

PMID- 14594794
TI  - Increase in vitamin B-12 during highly active antiretroviral therapy.

PMID- 14594792
TI  - Pathways: a school-based, randomized controlled trial for the prevention of
      obesity in American Indian schoolchildren.
AB  - BACKGROUND: Childhood obesity is a major public health problem in the United
      States, particularly among American Indian communities. OBJECTIVE: The objective
      was to evaluate the effectiveness of a school-based, multicomponent intervention
      for reducing percentage body fat in American Indian schoolchildren. DESIGN: This
      study was a randomized, controlled, school-based trial involving 1704 children in
      41 schools and was conducted over 3 consecutive years, from 3rd to 5th grades, in
      schools serving American Indian communities in Arizona, New Mexico, and South
      Dakota. The intervention had 4 components: 1) change in dietary intake, 2)
      increase in physical activity, 3) a classroom curriculum focused on healthy
      eating and lifestyle, and 4) a family-involvement program. The main outcome was
      percentage body fat; other outcomes included dietary intake, physical activity,
      and knowledge, attitudes, and behaviors. RESULTS: The intervention resulted in no
      significant reduction in percentage body fat. However, a significant reduction in
      the percentage of energy from fat was observed in the intervention schools. Total
      energy intake (by 24-h dietary recall) was significantly reduced in the
      intervention schools but energy intake (by direct observation) was not. Motion
      sensor data showed similar activity levels in both the intervention and control
      schools. Several components of knowledge, attitudes, and behaviors were also
      positively and significantly changed by the intervention. CONCLUSIONS: These
      results document the feasibility of implementing a multicomponent program for
      obesity prevention in elementary schools serving American Indian communities. The
      program produced significant positive changes in fat intake and in food- and
      health-related knowledge and behaviors. More intense or longer interventions may
      be needed to significantly reduce adiposity in this population.

PMID- 14594796
TI  - Expression of two Escherichia coli acetyl-CoA carboxylase subunits is
      autoregulated.
AB  - Acetyl-CoA carboxylase (ACC) catalyzes the first step of fatty acid biosynthesis,
      the synthesis of malonyl-CoA from acetyl-CoA using ATP and bicarbonate. In
      Escherichia coli and most other bacteria, ACC is composed of four subunits
      encoded by accA, accB, accC, and accD. Prior work from this laboratory showed
      that the in vivo expression of the accBC operon had a strikingly nonlinear
      response to gene copy number (Li, S.-J, and Cronan, J. E., Jr. (1993) J.
      Bacteriol. 175, 332-340) in that the presence of 50 or more copies of the accBC
      operon resulted in only a 2-3-fold increase in AccB and AccC. We now report that
      AccB functions to negatively regulate transcription of the accBC operon.
      Expression of a chimeric protein consisting of the N terminus of E. coli AccB and
      the C-terminal bioinylation domain of Bacillus subtilis AccB down-regulated
      transcription of the E. coli accBC operon. A truncated form of AccB consisting of
      the N-terminal 68 amino acids of E. coli AccB was sufficient to negatively
      regulate the accBC operon. In vivo bypass of acetyl-CoA carboxylase activity by
      expression of a malonyl-CoA synthase from Rhizobium trifolii allowed construction
      of strain deleted for the accA and accB genes. Unexpectedly, the deltaaccB
      mutation could not be resolved from the deltaaccA mutation. Transcription of the
      accBC operon in the deltaaccB deltaaccA strain continued well into stationary
      phase under growth conditions that normally result in greatly decreased
      transcription. These data support a model in which AccB acts as an autoregulator
      of accBC operon transcription.

PMID- 14594793
TI  - Acute effect of amino acid peritoneal dialysis solution on vascular function.
AB  - BACKGROUND: Oral ingestion of proteins or amino acids is associated with
      endothelial dysfunction. The effect of commercial amino acid peritoneal dialysis
      solutions on vascular function is unknown. OBJECTIVE: We compared the acute
      effect of intraperitoneal amino acid administration with that of intraperitoneal
      glucose administration on vascular function in peritoneal dialysis patients.
      DESIGN: In an open-label randomized, controlled, crossover and observer-blinded
      trial, we examined the acute effect of an intraperitoneal application of 2 L
      commercial 1.1% amino acid solution compared with that of a 2.27% glucose
      solution in 13 peritoneal dialysis patients. The primary endpoint was the change
      in forearm reactive hyperemia 6 h after instillation of either dialysis solution.
      RESULTS: After 6 h of dwell time, reactive hyperemia was substantially impaired
      after administration of the amino acid solution compared with the glucose
      solution (median difference: 202%; 95% CI: 57%, 368%; P = 0.007). In a comparison
      of differences between values at 6 h and those before treatment, reactive
      hyperemia significantly decreased during the dwell with the amino acid dialysis
      solution compared with that with the glucose dialysis solution (median
      difference: 242%; 95% CI: 53%, -457%; P = 0.013). In an analysis of smoking and
      nonsmoking patients separately, the difference in forearm blood flow between the
      2 treatments was still statistically significant. CONCLUSIONS: One 6-h dwell with
      a commercial amino acid dialysis solution acutely impairs forearm reactive
      hyperemia in smoking and nonsmoking peritoneal dialysis patients. Because
      endothelial dysfunction is associated with increased morbidity and mortality, the
      long-term use of these solutions may increase the risk of cardiovascular disease.

PMID- 14594797
TI  - Arginine 445 controls the coupling between glutamate and cations in the neuronal
      transporter EAAC-1.
AB  - The substrate-binding sites in membrane transporters are alternately accessible
      from either side of the membrane, but the molecular basis of how this alternate
      opening of internal and external gates is achieved is largely unknown. Here we
      present data indicating that, in the neuronal electrogenic sodium- and potassium
      coupled glutamate transporter EAAC-1, the substrate-binding site and one of the
      gates, or a residue controlling the gating process, are in close physical
      proximity. Arginine 445, located only two residues away from a residue implicated
      in glutamate binding (Bendahan, A., Armon, A., Madani, N., Kavanaugh, M. P., and
      Kanner, B. I. (2000) J. Biol. Chem. 275, 37436-37442), has been mutated to serine
      (R445S). Upon expression in oocytes, measurements of l-[(3)H]-glutamate transport
      under voltage clamp reveal that the charge/flux ratio for l-glutamate at -60 mV
      is approximately 30-fold higher than that of the wild type. Also, with d
      aspartate, R445S exhibits an approximately 15-fold increase in this ratio. In
      contrast to the wild type, the reversal potential of the substrate-dependent
      currents in R445S shifts to more negative potentials when either the external
      sodium or potassium concentration is decreased. These findings indicate that
      these two cations are the main current carriers in the R445S mutant. Introduction
      of a methionine or a glutamine, but not a lysine, at position 445 gives rise to a
      phenotype similar to R445S. Therefore, it seems that the elimination of a
      positive charge in the vicinity of the substrate-binding site converts the
      transporter into a glutamate-gated cation-conducting pathway.

PMID- 14594798
TI  - Interaction of human HSP22 (HSPB8) with other small heat shock proteins.
AB  - Mammalian small heat shock proteins (sHSP) are abundant in muscles and are
      implicated in both muscle function and myopathies. Recently a new sHSP, HSP22
      (HSPB8, H11), was identified in the human heart by its interaction with HSP27
      (HSPB1). Using phylogenetic analysis we show that HSP22 is a true member of the
      sHSP superfamily. sHSPs interact with each other and form homo- and hetero
      oligomeric complexes. The function of these complexes is poorly understood. Using
      gel filtration HPLC, the yeast two-hybrid method, immunoprecipitation, cross
      linking, and fluorescence resonance energy transfer microscopy, we report that
      (i). HSP22 forms high molecular mass complexes in the heart, (ii). HSP22
      interacts with itself, cvHSP (HSPB7), MKBP (HSPB2) and HSP27, and (iii). HSP22
      has two binding domains (N- and C-terminal) that are specific for different
      binding partners. HSP22 homo-dimers are formed through N-N and N-C interactions,
      and HSP22-cvHSP hetero-dimers through C-C interaction. HSP22-MKBP and HSP22-HSP27
      hetero-dimers involve the N and C termini of HSP22 and HSP27, respectively, but
      appear to require full-length protein as a binding partner.

PMID- 14594799
TI  - Constitutive and agonist-dependent self-association of the cell surface human
      lutropin receptor.
AB  - The human lutropin receptor (hLHR) is a G protein-coupled receptor (GPCR) that
      plays an essential role in reproductive physiology. The present studies were
      undertaken to determine whether the hLHR self-associates. We show that high
      molecular weight complexes of the hLHR can be co-immunoprecipitated from 293
      cells transfected with differentially tagged hLHRs. These complexes are detected
      only in extracts from cells that have been co-transfected and not in extracts
      combined from cells expressing only one form of tagged hLHR, confirming the in
      vivo self-association of the receptor. In transiently transfected cells, in which
      a small percentage of cells overexpress hLHR and most of the hLHR is located
      intracellularly in the ER, the self-associated hLHR is composed predominantly of
      immature hLHR. When cells were transiently co-transfected with wild-type hLHR and
      a misfolded mutant of the hLHR, a physical association of the ER-localized
      misfolded mutant with the immature hLHR was observed, resulting in a decreased
      cell surface expression of the wild-type receptor. In contrast, in stably
      transfected cells, where the majority of cells express receptor and there is much
      less intracellular accumulation of hLHR, the self-associated forms of the hLHR
      are composed predominantly of cell surface receptor. The abundance of cell
      surface hLHR dimers and oligomers, as detected on SDS gels, is increased further
      upon human choriogonadotropin treatment of the stably transfected cells. In
      addition to documenting the self-association of cell surface hLHR, our results
      underscore the importance of the cellular distribution of recombinant GPCR as it
      relates to the nature of the GPCR dimerization and oligomerization.

PMID- 14594800
TI  - Calmodulin binding to the Fas death domain. Regulation by Fas activation.
AB  - Fas (APO-1/CD95) is a cell surface receptor that initiates apoptotic pathways,
      and its cytoplasmic domain interacts with various molecules suggesting that Fas
      signaling is complex and regulated by multiple proteins. Calmodulin (CaM) is an
      intracellular Ca(2+)-binding protein, and it mediates many of the effects of
      Ca2+. Here, we demonstrate that CaM binds to Fas directly and identify the CaM
      binding site on the cytoplasmic death domain (DD) of Fas. Fas binds to CaM
      Sepharose and is co-immunoprecipitated with CaM. Other death receptors, such as
      tumor necrosis factor receptor, DR4, and DR5 do not bind to CaM. The interaction
      between Fas and CaM is Ca(2+)-dependent. Deletion mapping analysis with various
      GST-fused Fas cytoplasmic domain fragments revealed that the fragment containing
      helices 1, 2, and 3 of the Fas DD has the CaM-binding ability. Sequence analysis
      of this fragment predicted a potential CaM-binding site in helix 2 and connected
      loops. A valine 254 to asparagine mutation in this region, which is analogous to
      the identified mutant allele of Fas in lpr mice that have a deficiency in Fas
      mediated apoptosis, showed reduced CaM binding. Computer modeling of the
      interaction between CaM and helix 2 of the Fas DD predicted that amino acids,
      which are important for Fas-CaM binding, and point mutations of these amino acids
      caused reduced Fas-CaM binding. The interaction between Fas and CaM is increased
      approximately 2-fold early upon Fas activation (at 30 min) and is decreased to
      approximately 50% of control at 2 h. These findings suggest a novel function of
      CaM in Fas-mediated apoptosis.

PMID- 14594801
TI  - Modulating calcitonin fibrillogenesis: an antiparallel alpha-helical dimer
      inhibits fibrillation of salmon calcitonin.
AB  - We have investigated the prefibrillar state of salmon (s) and human (h)
      calcitonin (CT). Size exclusion chromatography at pH 3.3 and 7.4 indicates that
      sCT is present in solution as a dimer, whereas hCT elutes as a monomer at pH 3.3
      and as monomer-dimer at pH 7.4. Guanidine hydrochloride unfolding experiments
      show that dimerization is stabilized by hydrophobic interactions. We investigated
      the dimeric structure by multidimensional nuclear magnetic resonance spectroscopy
      and calculations by using an sCT mutant (LAsCT) in which Pro23 and Arg24 were
      substituted for Leu23 and Ala24. As indicated by the Leu9-Tyr27 and Leu12-Leu19
      contacts, the mutated hormone forms a head-to-tail dimer whose basic unit is an
      alpha-helix in the region Leu12-Tyr22. The solution behavior of LAsCT is
      identical to that of sCT, so the dimeric structure can safely be extended to sCT:
      we believe that such a structure inhibits fibril maturation in sCT. No stable
      dimer was observed for hCT, which we attributed to the absence of a defined
      helical structure. However, we suggest that intermolecular collisions of short
      ordered regions (for example, a sequence of turns) in hCT favors intermolecular
      contacts, and specific orientation can be obtained through hydrogen bond
      formation involving Tyr12, Phe16, and Phe19, with the aromatic ring acting as an
      acceptor. Taken together, our results indicate that hCT fibrillation can be
      reduced by favoring a helical dimer, obtainable by replacing the three aromatic
      amino acids with leucines.

PMID- 14594803
TI  - Genome-wide analysis of iron-dependent growth reveals a novel yeast gene required
      for vacuolar acidification.
AB  - We conducted a genome-wide screen in the budding yeast Saccharomyces cerevisiae
      of 4,792 homozygous diploid deletions to identify genes that function in iron
      metabolism. Strains unable to grow on iron-restricted medium contained deletions
      of genes that encode the structural components of the high affinity iron
      transport system (FET3, FTR1), the iron-sensing transcription factor AFT1 or
      genes required for the assembly of the transport system. We also identified genes
      that were not previously known to play a role in iron metabolism. Deletion of the
      gene CWH36 resulted in a severe growth defect on iron-limited medium, as well as
      increased sensitivity to Congo red and calcofluor white. Iron transport studies
      demonstrated that Deltacwh36 cells have an inability to copper load apoFet3p.
      Furthermore, Deltacwh36 cells demonstrated additional phenotypes including
      distorted vacuole morphology and altered kinetics of FM4-64 trafficking. We show
      that Deltacwh36 cells have a defect in vacuolar acidification through the use of
      the pH-sensitive dye LysoSensor Green DND-189. In Deltacwh36 cells, the vacuolar
      H+-ATPase is not assembled and there are reduced levels of at least one subunit
      of the V0 complex. The open reading frame responsible for the Deltacwh36
      phenotypes is YCL005W-A. This gene contains two introns, has homologues in other
      Saccharomyces strains, and shows weak homology to a component of the vacuolar H+
      ATPase found in organisms as diverse as insect and cow.

PMID- 14594802
TI  - Lymphoid enhancer factor-1 links two hereditary leukemia syndromes through core
      binding factor alpha regulation of ELA2.
AB  - Two hereditary human leukemia syndromes are severe congenital neutropenia (SCN),
      caused by mutations in the gene ELA2, encoding the protease neutrophil elastase,
      and familial platelet disorder with acute myelogenous leukemia (AML), caused by
      mutations in the gene AML1, encoding the transcription factor core-binding factor
      alpha (CBFalpha). In mice, CBFalpha regulates the expression of ELA2, suggesting
      a common link for both diseases. However, gene-targeted mouse models have failed
      to reproduce either human disease, thus prohibiting further in vivo studies in
      mice. Here we investigate CBFalpha regulation of the human ELA2 promoter, taking
      advantage of bone marrow obtained from patients with either illness. In
      particular, we have identified novel ELA2 promoter substitutions (-199 C to A)
      within a potential motif for lymphoid enhancer factor-1 (LEF-1), a
      transcriptional mediator of Wnt/beta-catenin signaling, in SCN patients. The LEF
      1 motif lies adjacent to a potential CBFalpha binding site that is in a different
      position in human compared with mouse ELA2. We find that LEF-1 and CBFalpha co
      activate ELA2 expression. In vitro, the high mobility group domain of LEF-1
      interacts with the runt DNA binding and proline-, serine-, threonine-rich
      activation domains of CBFalpha. ELA2 transcript levels are up-regulated in bone
      marrow of an SCN patient with the -199 C to A substitution. Conversely, a
      mutation of the CBFalpha activation domain, found in a patient with familial
      platelet disorder with AML, fails to stimulate the ELA2 promoter in vitro, and
      bone marrow correspondingly demonstrates reduced ELA2 transcript. Observations in
      these complementary patients indicate that LEF-1 cooperates with CBFalpha to
      activate ELA2 in vivo and also suggest the possibility that up-regulating
      promoter mutations can contribute to SCN. Two hereditary AML predisposition
      syndromes may therefore intersect via LEF-1, potentially linking them to more
      generalized cancer mechanisms.

PMID- 14594804
TI  - The contribution of the exosite residues of plasminogen activator inhibitor-1 to
      proteinase inhibition.
AB  - The binding of plasminogen activator inhibitor-1 (PAI-1) to serine proteinases,
      such as tissue-type plasminogen activator (tPA) and urokinase-type plasminogen
      activator (uPA), is mediated by the exosite interactions between the surface
      exposed variable region-1, or 37-loop, of the proteinase and the distal reactive
      center loop (RCL) of PAI-1. Although the contribution of such interactions to the
      inhibitory activity of PAI-1 has been established, the specific mechanistic steps
      affected by interactions at the distal RCL remain unknown. We have used protein
      engineering, stopped-flow fluorimetry, and rapid acid quenching techniques to
      elucidate the role of exosite interactions in the neutralization of tPA, uPA, and
      beta-trypsin by PAI-1. Alanine substitutions at the distal P4' (Glu-350) and P5'
      (Glu-351) residues of PAI-1 reduced the rates of Michaelis complex formation
      (k(a)) and overall inhibition (k(app)) with tPA by 13.4- and 4.7-fold,
      respectively, whereas the rate of loop insertion or final acyl-enzyme formation
      (k(lim)) increased by 3.3-fold. The effects of double mutations on k(a), k(lim),
      and k(app) were small with uPA and nonexistent with beta-trypsin. We provide the
      first kinetic evidence that the removal of exosite interactions significantly
      alters the formation of the noncovalent Michaelis complex, facilitating the
      release of the primed side of the distal loop from the active-site pocket of tPA
      and the subsequent insertion of the cleaved reactive center loop into beta-sheet
      A. Moreover, mutational analysis indicates that the P5' residue contributes more
      to the mechanism of tPA inhibition, notably by promoting the formation of a final
      Michaelis complex.

PMID- 14594805
TI  - Distinct structural determinants of efficacy and sensitivity in the ligand
      binding domain of cyclic nucleotide-gated channels.
AB  - Cyclic nucleotide-gated (CNG) channels open in response to direct binding of
      cyclic nucleotide messengers. Every subunit in a tetrameric CNG channel contains
      a cytoplasmic ligand-binding domain (BD) that includes a beta-roll (flanked by
      short helices) and a single C-terminal helix called the C-helix that was
      previously found to control efficacy (maximal open probability) and selectivity
      for cGMP versus cAMP. We constructed a series of chimeric CNG channel subunits,
      each containing a distinct BD sequence (chosen from among six phylogenetically
      divergent isoforms) fused to an invariant non-BD sequence. We assayed these "BD
      substitution" chimeras as homomeric CNG channels in Xenopus oo-cytes to compare
      their functions and found that the most efficient activation by both cAMP and
      cGMP derived from the BD of the catfish CNGA4 olfactory modulatory subunit
      (fCNGA4). We then tested the effects of replacing subregions of the bovine CNGA1
      BD with corresponding fCNGA4 sequence and hence identified parts of the fCNGA4 BD
      producing efficient activation. For instance, replacing either the "hinge" that
      connects the roll and C-helix subdomains or the BD sequence N-terminal to the
      hinge greatly enhanced cAMP efficacy. Replacing the "loop-beta 8" region (the C
      terminal end of the beta-roll) improved agonist sensitivity for cGMP selectively
      over cAMP. Our results thus identify multiple BD elements outside the C-helix
      that control selective ligand interaction and channel gating steps by distinct
      mechanisms. This suggests that the purine ring of the cyclic nucleotide may
      interact with both the beta-roll and the C-helix at different points in the
      mechanism.

PMID- 14594807
TI  - Functional diversity of the rhodanese homology domain: the Escherichia coli ybbB
      gene encodes a selenophosphate-dependent tRNA 2-selenouridine synthase.
AB  - Escherichia coli has eight genes predicted to encode sulfurtransferases having
      the active site consensus sequence Cys-Xaa-Xaa-Gly. One of these genes, ybbB, is
      frequently found within bacterial operons that contain selD, the selenophosphate
      synthetase gene, suggesting a role in selenium metabolism. We show that ybbB is
      required in vivo for the specific substitution of selenium for sulfur in 2
      thiouridine residues in E. coli tRNA. This modified tRNA nucleoside, 5
      methylaminomethyl-2-selenouridine (mnm(5)se(2)U), is located at the wobble
      position of the anticodons of tRNA(Lys), tRNA(Glu), and tRNA(1)(Gln). Nucleoside
      analysis of tRNAs from wild-type and ybbB mutant strains revealed that production
      of mnm(5)se(2)U is lost in the ybbB mutant but that 5-methylaminomethyl-2
      thiouridine, the mnm(5)se(2)U precursor, is unaffected by deletion of ybbB. Thus,
      ybbB is not required for the initial sulfurtransferase reaction but rather
      encodes a 2-selenouridine synthase that replaces a sulfur atom in 2-thiouridine
      in tRNA with selenium. Purified 2-selenouridine synthase containing a C-terminal
      His(6) tag exhibited spectral properties consistent with tRNA bound to the
      enzyme. In vitro mnm(5)se(2)U synthesis is shown to be dependent on 2
      selenouridine synthase, SePO(3), and tRNA. Finally, we demonstrate that the
      conserved Cys(97) (but not Cys(96)) in the rhodanese sequence motif Cys(96)
      Cys(97)-Xaa-Xaa-Gly is required for 2-selenouridine synthase in vivo activity.
      These data are consistent with the ybbB gene encoding a tRNA 2-selenouridine
      synthase and identifies a new role for the rhodanese homology domain in enzymes.

PMID- 14594806
TI  - Structural basis for endosomal targeting by FYVE domains.
AB  - The FYVE domain is a conserved protein motif characterized by its ability to bind
      with high affinity and specificity to phosphatidylinositol 3-phosphate (PI3P), a
      phosphoinositide highly enriched in early endosomes. The PI3P polar head group
      contacts specific amino acid residues that are conserved among FYVE domains.
      Despite full conservation of these residues, the ability of different FYVE
      domains to bind to endosomes in cells is highly variable. Here we show that the
      endosomal localization in intact cells absolutely requires structural features
      intrinsic to the FYVE domain in addition to the PI3P binding pocket. These
      features are involved in FYVE domain dimerization and in interaction with the
      membrane bilayer. These interactions, which are determined by non-conserved
      residues, are likely to be essential for the temporal and spatial control of
      protein associations at the membrane-cytosol interface within the endocytic
      pathway.

PMID- 14594808
TI  - The Pol32 subunit of DNA polymerase delta contains separable domains for
      processive replication and proliferating cell nuclear antigen (PCNA) binding.
AB  - We have carried out a domain analysis of POL32, the third subunit of
      Saccharomyces cerevisiae DNA polymerase delta (Pol delta). Interactions with
      POL31, the second subunit of Pol delta, are specified by the amino-terminal 92
      amino acids, whereas interactions with the replication clamp proliferating cell
      nuclear antigen (PCNA, POL30) reside at the extreme carboxyl-terminal region.
      Pol32 binding, in vivo and in vitro, to the large subunit of DNA polymerase
      alpha, POL1, requires the carboxyl-proximal region of Pol32. The amino-terminal
      region of Pol32 is essential for damage-induced mutagenesis. However, the
      presence of its carboxyl-terminal PCNA-binding domain enhances the efficiency of
      mutagenesis, particularly at high loads of DNA damage. In vitro, in the absence
      of effector DNA, the PCNA-binding domain of Pol32 is essential for PCNA-Pol delta
      interactions. However, this domain has minimal importance for processive DNA
      synthesis by the ternary DNA-PCNA-Pol delta complex. Rather, processivity is
      determined by PCNA-binding domains located in the Pol3 and/or Pol31 subunits.
      Using diagnostic PCNA mutants, we show that during DNA synthesis the carboxyl
      terminal domain of Pol32 interacts with the carboxyl-terminal region of PCNA,
      whereas interactions of the other subunit(s) of Pol delta localize largely to a
      hydrophobic pocket at the interdomain connector loop region of PCNA.

PMID- 14594809
TI  - Interaction of the TAZ1 domain of the CREB-binding protein with the activation
      domain of CITED2: regulation by competition between intrinsically unstructured
      ligands for non-identical binding sites.
AB  - The TAZ1 domain of the homologous transcriptional coactivators CREB-binding
      protein (CBP) and p300 forms a complex with CITED2 (CBP/p300-interacting
      transactivator with ED-rich tail), inhibiting the activity of the hypoxia
      inducible factor (HIF-1alpha) and thereby attenuating the cellular response to
      low tissue oxygen concentration. We report the NMR structure of the CBP TAZ1
      domain bound to the activation domain of CIT-ED2. The structure of TAZ1,
      consisting of four alpha-helices (alpha(1)-alpha(4)) stabilized by three zinc
      atoms, is very similar in the CITED2 and HIF-1alpha complexes. The activation
      domain of CITED2 is unstructured when free and folds upon binding, forming a
      helix (termed alpha(A)) and an extended structure that wraps around TAZ1. The
      CITED2 alpha(A) helix packs in the TAZ1 alpha(1)/alpha(4) interface, a site that
      forms weak interactions with the poorly defined aminoterminal alpha-helix of HIF
      1alpha. CITED2 and HIF-1alpha both contain a four residue motif, LP(E/Q)L, which
      binds in the TAZ1 alpha(1)/alpha(2)/alpha(3) junction in each complex. The
      carboxyl-terminal region of CITED2 forms an extended structure with hydrophobic
      contacts in the TAZ1 alpha(1)/alpha(3) interface in the site occupied by the HIF
      1alpha alpha(B) helix. CITED2 does not bind at all to the TAZ1 site occupied by
      the HIF-1alpha carboxyl-terminal helix. The HIF-1alpha and CITED2 domains utilize
      partly overlapping surfaces of TAZ1 to achieve high affinity binding and to
      compete effectively with each other for interaction with CBP/p300; CITED2 and HIF
      1alpha use these binding sites differently to maintain similar binding affinities
      in order to displace each other in a feedback loop during the hypoxic response.

PMID- 14594810
TI  - The role of lysine 532 in the catalytic mechanism of human topoisomerase I.
AB  - Based on co-crystal structures of human topoisomerase I with bound DNA, Lys(532)
      makes a minor groove contact with the strongly preferred thymidine residue at the
      site of covalent attachment (-1 position). Replacement of Lys(532) with either
      arginine or alanine has essentially no effect on the sequence preference of the
      enzyme, indicating that this interaction is not required for the preference for a
      T at the -1 position. Although both the cleavage and religation activities of the
      K532R mutant enzyme are reduced, cleavage is reduced to a greater extent than
      religation. The reverse is true for the K532A mutant enzyme with religation so
      impaired that the nicked intermediate accumulates during plasmid relaxation
      assays. Consistent with the shift in the cleavage religation equilibrium toward
      cleavage for the K532A mutant enzyme, expression of the mutant enzyme in
      Saccharomyces cerevisiae is cytotoxic, and thus this mutant enzyme mimics the
      effects of the anticancer drug camptothecin. Cleavage assays with the mutant
      enzymes using an oligonucleotide containing a 5'-bridging phosphorothiolate
      indicate that Lys(532) functions as a general acid during cleavage to protonate
      the leaving 5'-oxygen. It is possible that the contact with the -1 base is
      important during catalysis to provide positional rigidity to the active site. The
      corresponding residues in the vaccinia virus topoisomerase and the tyrosine
      recombinases may have similar critical roles in catalysis.

PMID- 14594811
TI  - Investigations into calcium-dependent membrane association of 15-lipoxygenase-1.
      Mechanistic roles of surface-exposed hydrophobic amino acids and calcium.
AB  - Among mammalian lipoxygenases the 15-lipoxygenase-1 is somewhat special because
      of its capability of oxygenating complex lipid-protein assemblies (biomembranes,
      lipoproteins) and previous investigations have implicated calcium in
      enzyme/membrane interaction. We investigated the mechanism of calcium-dependent
      membrane association and obtained the following results. (i) Membrane binding of
      15-lipoxygenase-1 involves electrostatic forces as well as hydrophobic
      interactions of solvent-exposed apolar amino acids (Tyr(15), Phe(70), Leu(71),
      Trp(181), and Leu(195)) with the hydrophobic core of membrane phospholipids.
      These sequence determinants of membrane association are clustered at the membrane
      contact plane of the enzyme that also involves the entrance to the substrate
      binding pocket. Site-directed mutagenesis of these determinants to negatively
      charged residues strongly impaired membrane binding. (ii) Calcium at micromolar
      concentrations (5-50 microM) is required for efficient membrane binding. For
      direct 15-lipoxygenase/calcium interaction a dissociation constant of 2-5 x 10(
      4) m was determined (low affinity binding) and we failed to detect high affinity
      calcium-binding sites at the enzyme. Reversible low affinity calcium binding
      induces subtle structural alterations of the enzyme, which did not impact
      catalytic activity. (iii) Increasing calcium concentrations failed to reverse
      impairment of membrane binding induced by mutagenesis of the sequence
      determinants indicating the priority of hydrophobic interactions. Taken together
      these data suggest that 15-lipoxygenase-1 associates to biomembranes primarily
      via hydrophobic interactions between surface-exposed apolar amino acid side
      chains and membrane lipids. Calcium supports membrane binding probably by forming
      salt bridges between the negatively charged head groups of membrane phospholipids
      and acidic surface amino acids of the membrane contact plane and this interaction
      might contribute to overcome repulsive forces.

PMID- 14594812
TI  - Arabidopsis phospholipase Dalpha1 interacts with the heterotrimeric G-protein
      alpha-subunit through a motif analogous to the DRY motif in G-protein-coupled
      receptors.
AB  - Phospholipase D (PLD) and heterotrimeric G-protein both play important, diverse
      roles in cellular regulation and signal transduction. Here we have determined the
      physical interaction between plant PLD and the only canonical alpha-subunit
      (Galpha) of the G-protein in Arabidopsis thaliana and the molecular basis for the
      interaction. PLDalpha1 expressed in either Escherichia coli or Arabidopsis was co
      precipitated with Galpha. PLDalpha1 contains a sequence motif analogous to the G
      alpha-interacting DRY motif normally conserved in G-protein-coupled receptors.
      Mutation of the central Lys residue PLD(K564A) of this motif abolished the
      PLDalpha1-Galpha binding, whereas mutation of the two flanking residues
      PLD(E563A) and PLD(F565A) decreased the binding. Addition of Galpha to PLDalpha1
      inhibited PLDalpha1 activity, whereas the PLD(K564A) mutation that disrupted the
      Galpha-PLDalpha1 binding abolished the inhibition. GTP relieved the Galpha
      inhibition of PLDalpha1 activity and also inhibited the binding between PLDalpha1
      and Galpha. Meanwhile, the PLDalpha1-Galpha interaction stimulated the intrinsic
      GTPase activity of Galpha. Therefore, these results have demonstrated the direct
      binding between Galpha and PLDalpha1, identified the DRY motif on PLDalpha1 as
      the site for the interaction, and indicated that the interaction modulates
      reciprocally the activities of PLDalpha1 and Galpha.

PMID- 14594813
TI  - Characterization of the protein kinase activity of TRPM7/ChaK1, a protein kinase
      fused to the transient receptor potential ion channel.
AB  - Channel-kinase TRPM7/ChaK1 is a member of a recently discovered family of protein
      kinases called alpha-kinases that display no sequence homology to conventional
      protein kinases. It is an unusual bifunctional protein that contains an alpha
      kinase domain fused to an ion channel. The TRPM7/ChaK1 channel has been
      characterized using electrophysiological techniques, and recent evidence suggests
      that it may play a key role in the regulation of magnesium homeostasis. However,
      little is known about its protein kinase activity. To characterize the kinase
      activity of TRPM7/ChaK1, we expressed the kinase catalytic domain in bacteria.
      ChaK1-cat is able to undergo autophosphorylation and to phosphorylate myelin
      basic protein and histone H3 on serine and threonine residues. The kinase is
      specific for ATP and cannot use GTP as a substrate. ChaK1-cat is insensitive to
      staurosporine (up to 0.1 mM) but can be inhibited by rottlerin. Because the
      kinase domain is physically linked to an ion channel, we investigated the effect
      of ions on ChaK1-cat activity. The kinase requires Mg(2+) (optimum at 4-10 mM) or
      Mn(2+) (optimum at 3-5 mM), with activity in the presence of Mn(2+) being 2
      orders of magnitude higher than in the presence of Mg(2+). Zn(2+) and Co(2+)
      inhibited ChaK1-cat kinase activity. Ca(2+) at concentrations up to 1 mM did not
      affect kinase activity. Considering intracellular ion concentrations, our results
      suggest that, among divalent metal ions, only Mg(2+) can directly modulate
      TRPM7/ChaK1 kinase activity in vivo.

PMID- 14594814
TI  - Unique in vivo modifications of coagulation factor V produce a physically and
      functionally distinct platelet-derived cofactor: characterization of purified
      platelet-derived factor V/Va.
AB  - Platelet- and plasma-derived factor Va (FVa) serve essential cofactor roles in
      prothrombinase-catalyzed thrombin generation. Platelet-derived FV/Va, purified
      from Triton X-100 platelet lysates was composed of a mixture of polypeptides
      ranging from approximately 40 to 330 kDa, mimicking those visualized by Western
      blotting of platelet lysates and releasates with anti-FV antibodies. The
      purified, platelet-derived protein expressed significant cofactor activity such
      that thrombin activation led to only a 2-3-fold increase in cofactor activity yet
      expression of a specific activity identical to that of purified, plasma-derived
      FVa. Physical and functional differences between the two cofactors were
      identified. Purified, platelet-derived FVa was 2-3-fold more resistant to
      activated protein C-catalyzed inactivation than purified plasma-derived FVa on
      the thrombin-activated platelet surface. The heavy chain subunit of purified,
      platelet-derived FVa contained only a fraction ( approximately 10-15%) of the
      intrinsic phosphoserine present in the plasma-derived FVa heavy chain and was
      resistant to phosphorylation at Ser(692) catalyzed by either casein kinase II or
      thrombin-activated platelets. MALDI-TOF mass spectrometric analyses of tryptic
      digests of platelet-derived FV peptides detected an intact heavy chain uniquely
      modified on Thr(402) with an N-acetylglucosamine or N-acetylgalactosamine,
      whereas Ser(692) remained unmodified. N-terminal sequencing and MALDI-TOF
      analyses of platelet-derived FV/Va peptides identified the presence of a full
      length heavy chain subunit, as well as a light chain subunit formed by cleavage
      at Tyr(1543) rather than Arg(1545) accounting for the intrinsic levels of
      cofactor activity exhibited by native platelet-derived FVa. These collective data
      are the first to demonstrate physical differences between the two FV cofactor
      pools and support the hypothesis that, subsequent to its endocytosis by
      megakaryocytes, FV is modified to yield a platelet-derived cofactor distinct from
      its plasma counterpart.

PMID- 14594815
TI  - A new function of the Desulfovibrio vulgaris Hildenborough [Fe] hydrogenase in
      the protection against oxidative stress.
AB  - Sulfate-reducing bacteria, like Desulfovibrio vulgaris Hildenborough, have
      developed a set of reactions allowing them to survive in oxic environments and
      even to reduce molecular oxygen to water. D. vulgaris contains a cytoplasmic
      superoxide reductase (SOR) and a periplasmic superoxide dismutase (SOD) involved
      in the elimination of superoxide anions. To assign the function of SOD, the
      periplasmic [Fe] hydrogenase activity was followed in both wild-type and sod
      deletant strains. This activity was lower in the strain lacking the SOD than in
      the wild-type when the cells were exposed to oxygen for a short time. The
      periplasmic SOD is thus involved in the protection of sensitive iron-sulfur
      containing enzyme against superoxide-induced damages. Surprisingly, production of
      the periplasmic [Fe] hydrogenase was higher in the cells exposed to oxygen than
      in those kept in anaerobic conditions. A similar increase in the amount of [Fe]
      hydrogenase was observed when an increase in the redox potential was induced by
      addition of chromate. Viability of the strain lacking the gene encoding [Fe]
      hydrogenase after exposure to oxygen for 1 h was lower than that of the wild
      type. These data reveal for the first time that production of the periplasmic
      [Fe] hydrogenase is up-regulated in response to an oxidative stress. A new
      function of the periplasmic [Fe] hydrogenase in the protective mechanisms of D.
      vulgaris Hildenborough toward an oxidative stress is proposed.

PMID- 14594816
TI  - Identification of two cyclooxygenase active site residues, Leucine 384 and
      Glycine 526, that control carbon ring cyclization in prostaglandin biosynthesis.
AB  - The cyclooxygenase (COX) reaction of prostaglandin (PG) biosynthesis begins with
      the highly specific oxygenation of arachidonic acid in the 11R configuration and
      ends with a 15S oxygenation to form PGG2. To obtain new insights into the
      mechanisms of stereocontrol of oxygenation, we mutated active site residues of
      human COX-2 that have potential contacts with C-11 of the reacting substrate.
      Although the 11R oxygenation was not perturbed, changing Leu-384 (into Phe, Trp),
      Trp-387 (Phe, Tyr), Phe-518 (Ile, Trp, Tyr), and Gly-526 (Ala, Ser, Thr, Val)
      impaired or abrogated PGG2 synthesis, and typically 11R-HETE was the main product
      formed. The Gly-526 and Leu-384 mutants formed, in addition, three novel products
      identified by LC-MS, NMR, and circular dichroism as 8,9-11,12-diepoxy-13R-(or
      15R)-hydro(pero)xy derivatives of arachidonic acid. Mechanistically, we propose
      these arise from a free radical intermediate in which a C-8 carbon radical
      displaces the 9,11-endoperoxide O-O bond to yield an 8,9-11,12-diepoxide that is
      finally oxygenated stereospecifically in the 13R or 15R configuration. Formation
      of these novel products signals an arrest in the normal course of prostaglandin
      synthesis just prior to closing of the 5-membered carbon ring, and points to a
      crucial role for Leu-384 and Gly-526 in the correct positioning of the reacting
      fatty acid intermediate. Some of the Gly-526 and Leu-384 mutants catalyzed both
      formation of PGG2 (with the normal 15S configuration) and the 13R- or 15R
      oxygenated diepoxides. This result suggests that oxygenation specificity can be
      determined by the orientation of the reacting fatty acid radical and is not a
      predetermined outcome based solely on the structure of the cyclooxygenase active
      site.

PMID- 14594818
TI  - CD40 stimulation induces Pax5/BSAP and EBF activation through a APE/Ref-1
      dependent redox mechanism.
AB  - CD40 is a member of the growing tumor necrosis factor receptor family that has
      been shown to play important roles in T cell-mediated B lymphocyte activation.
      Ligation of B cell CD40 by CD154, mainly expressed on activated T cells,
      stimulates B cell proliferation, differentiation, isotype switching, up
      regulation of surface molecules contributing to antigen presentation, development
      of the germinal center, and the humoral memory response. In this study we
      demonstrate that the redox factor APE/Ref-1 acts as a key signaling intermediate
      in response to CD40-mediated B cell activation. The transcription factors Pax5a
      or BSAP (B cell lineage-specific activator protein) and EBF (early B cell factor)
      are constitutively expressed in spleen B cells and CD40 cross-linking induces
      increases in Pax5a and EBF binding activity compared with nonstimulated B cells.
      We show that upon CD40 antibody-mediated cross-linking, APE/Ref-1 translocates
      from the cytoplasm to the nucleus of activated B cells, where it modulates the
      DNA binding activity of both Pax5a and EBF. Moreover, we show that the repression
      of APE/Ref-1 protein production is able to block CD40-mediated Pax5a activation.
      We also provide evidence that APE/Ref-1 can modulate the cooperative activation
      of the blk promoter operated by Pax5a and EBF and that APE/Ref-1 might directly
      regulate EBF functional activity. Finally, we show that the interaction between
      Pax5a and EBF enhances EBF binding activity to its consensus sequence, suggesting
      that Pax5a can physically interact with EBF and modulate its DNA binding
      activity.

PMID- 14594817
TI  - Identification of a novel class of endoperoxides from arachidonate autoxidation.
AB  - Free radical-initiated lipid autoxidation in low density lipoprotein (LDL) has
      been implicated in the pathogenesis of atherosclerosis. Oxidation of the lipid
      components of LDL leads to a complex mixture of hydroperoxides, bicyclic
      endoperoxides, monocyclic peroxides, and serial cyclic peroxides. The oxidation
      compounds and/or their decomposition products can modify protein components,
      which may lead to various diseases. A novel class of peroxides (termed dioxolane
      isoprostanes) having a bicyclic endoperoxide moiety characteristic of the
      isoprostanes and a dioxolane peroxide functionality in the same molecule was
      identified in the product mixture formed from in vitro autoxidation of
      cholesteryl arachidonate. The same products are also detected in in vitro
      oxidized LDL. Various mass spectrometric techniques have been applied to
      characterize these new peroxides. The structure of these compounds has also been
      confirmed by independent synthesis. We reason, based on the free radical
      mechanism of the transformation, that only the 12- and 8-peroxyl radicals (those
      leading to 12-HPETE and 8-HPETE) of arachidonate can form these new peroxides. We
      also suggest that the formation of these peroxides provides a rationale to
      explain the fact that 5- and 15-series isoprostanes are formed in preference to 8
      and 12-series. Furthermore, series of other isoprostanes, such as dioxolane
      A(2), D(2), E(2), etc., can be derived from the dioxolane-isoprostane peroxides.
      These findings offer further insights into the oxidation products of arachidonate
      and the opportunity to study their potential biological relevance.

PMID- 14594820
TI  - Chloroplast biogenesis 88. Protochlorophyllide b occurs in green but not in
      etiolated plants.
AB  - It has recently been reported that protochlorophyllide (Pchlide) b is an abundant
      pigment in barley etioplasts but is rather unstable, as it is rapidly converted
      to Pchlide a by 7-formyl reductase during pigment extraction with conventional
      80% acetone (Reinbothe, S., Pollmann, S., and Reinbothe, C. (2003) J. Biol. Chem.
      278, 800-806). It has also been claimed that extraction of barley etioplasts with
      100% acetone containing 0.1% diethyl pyrocarbonate prevents the conversion of
      Pchlide b to Pchlide a and leads to the detection of large amounts of Pchlide b
      in the isolated etioplasts. In this work the extraction protocol of Reinbothe et
      al. is compared with the more conventional 80% aqueous acetone extraction method.
      No Pchlide b was detected either in etiolated barley leaves or isolated barley
      etioplasts irrespective of the extraction protocol. On the other hands, small
      amounts of Pchlide b were detected in green barley leaves and isolated
      chloroplasts, extracted either with 80% acetone or 100% acetone containing 0.1%
      diethyl pyrocarbonate. It is concluded that the proposed occurrence of a light
      harvesting POR-Pchlide-a,b complex in etiolated plant tissues is untenable, and
      its ensuing consequences and implications, for the greening process, are
      irrelevant.

PMID- 14594819
TI  - Dynamic regulation of the inducible nitric-oxide synthase by NO: comparison with
      the endothelial isoform.
AB  - We studied by ultrafast time-resolved absorption spectroscopy the geminate
      recombination of NO to the oxygenase domain of the inducible NO synthase,
      iNOSoxy, and to mutated proteins at position Trp-457. This tryptophan interacts
      with the tetrahydrobiopterin cofactor BH4, and W457A/F mutations largely reduced
      the catalytic formation of NO. BH4 decreases the rate of NO rebinding to the
      ferric iNOSoxy compared with that measured in its absence. The pterin has a
      larger effect on W457A/F than on the WT protein by increasing NO release from the
      protein. Therefore, BH4 raises the energy barrier for NO recombination to the
      mutated proteins in contrast with our observations on eNOS (Slama-Schwok, A.,
      Negrerie, M., Berka, V., Lambry, J.-C., Tsai, A.-L., Vos, M., and Martin, J.-L.
      (2002) J. Biol. Chem. 277, 7581-7586). Thus, we show a differential effect of BH4
      on NO release from eNOS and iNOS. Compared with the position of this residue in
      the BH4-repleted enzyme, simulations of the NO dissociation dynamics point out at
      a swing of Trp-457 toward the missing pterin in the absence of BH4. NO geminate
      rebinding data show a more efficient NO release from eNOS than from iNOS once NO
      is formed. Consistently, NO produced by iNOS is regulated by its ferric nitrosyl
      complex in contrast with eNOS. We show that the small enhancement of the NO
      geminate recombination rate in W457A/F compared with that in the WT enzyme cannot
      explain the decrease of NO yield because of the mutation; the major effect of the
      mutation thus arises from an uncoupled catalysis (Wang, Z. Q., Wei, C. C., Ghosh,
      S., Meade, A. L., Hemann, C., Hille, R., and Stuehr, D. J. (2001) Biochemistry
      40, 12819-12825).

PMID- 14594821
TI  - Negative osmoregulation of the Salmonella ompS1 porin gene independently of OmpR
      in an hns background.
AB  - The ompS1 gene encodes a quiescent porin in Salmonella enterica serovars Typhi
      and Typhimurium. By using random mariner transposon mutagenesis, mutations that
      caused derepression of ompS1 expression were isolated, one in S. enterica serovar
      Typhi and two in S. enterica serovar Typhimurium. All of them mapped in the hns
      gene in the region coding for the carboxy terminus of the H-NS nucleoid protein.
      The derepressed ompS1 expression was subject to negative regulation at high
      osmolarity, both in the presence and in the absence of OmpR. This observation was
      possible due to the fact that there are two promoters: P1, which is OmpR
      dependent, and P2, which does not require OmpR for activation (rather, OmpR
      represses P2). The sequences upstream from position -88, a region previously
      shown to be involved in the negative regulation of ompS1, can form a static bend,
      and the integrity of this region was required for function and binding of H-NS
      and for osmoregulation, as determined with gene reporter fusions of different
      lengths and with a 31-bp deletion mutant. This is consistent with the notion that
      this region determines a structure required for repression. Hence, ompS1 shares
      negative regulation by H-NS with other loci, such as the bgl operon and the ade
      gene.

PMID- 14594822
TI  - Functional and biochemical analysis of Chlamydia trachomatis MurC, an enzyme
      displaying UDP-N-acetylmuramate:amino acid ligase activity.
AB  - Chlamydiae are unusual obligate intracellular bacteria that cause serious
      infections in humans. Chlamydiae contain genes that appear to encode products
      with peptidoglycan biosynthetic activity. The organisms are also susceptible to
      antibiotics that inhibit peptidoglycan synthesis. However, chlamydiae do not
      synthesize detectable peptidoglycan. The paradox created by these observations is
      known as the chlamydial anomaly. The MurC enzyme of chlamydiae, which is
      synthesized as a bifunctional MurC-Ddl product, is expected to possess UDP-N
      acetylmuramate (UDP-MurNAc):L-alanine ligase activity. In this paper we
      demonstrate that the MurC domain of the Chlamydia trachomatis bifunctional
      protein is functionally expressed in Escherichia coli, since it complements a
      conditional lethal E. coli mutant possessing a temperature-sensitive lesion in
      MurC. The recombinant MurC domain was overexpressed in and purified from E. coli.
      It displayed in vitro ATP-dependent UDP-MurNAc:L-alanine ligase activity, with a
      pH optimum of 8.0 and dependence upon magnesium ions (optimum concentration, 20
      mM). Its substrate specificity was studied with three amino acids (L-alanine, L
      serine, and glycine); comparable Vmax/Km values were obtained. Our results are
      consistent with the synthesis of a muramic acid-containing polymer in chlamydiae
      with UDP-MurNAc-pentapeptide as a precursor molecule. However, due to the lack of
      specificity of MurC activity in vitro, it is not obvious which amino acid is
      present in the first position of the pentapeptide.

PMID- 14594823
TI  - Identification and characterization of phytoplasmal genes, employing a novel
      method of isolating phytoplasmal genomic DNA.
AB  - Phytoplasmas are unculturable, insect-transmissible plant pathogens belonging to
      the class Mollicutes. To be transmitted, the phytoplasmas replicate in the insect
      body and are delivered to the insect's salivary glands, from where they are
      injected into the recipient plant. Because phytoplasmas cannot be cultured, any
      attempt to recover phytoplasmal DNA from infected plants or insects has resulted
      in preparations with a large background of host DNA. Thus, studies of the
      phytoplasmal genome have been greatly hampered, and aside from the rRNA genes,
      only a few genes have hitherto been isolated and characterized. We developed a
      unique method to obtain host-free phytoplasmal genomic DNA from the insect
      vector's saliva, and we demonstrated the feasibility of this method by isolating
      and characterizing 78 new putative phytoplasmal open reading frames and their
      deduced proteins. Based on the newly accumulated information on phytoplasmal
      genes, preliminary characteristics of the phytoplasmal genome are discussed.

PMID- 14594824
TI  - Cosmid-based system for transient expression and absolute off-to-on
      transcriptional control of Escherichia coli genes.
AB  - Cosmids are plasmids that contain the phage lambda sequences (cos) required for
      packaging of the phage DNA into the virion. Induction of a lambda prophage in an
      Escherichia coli strain carrying a cosmid results in lysates containing phage
      particles that are filled with cosmid DNA. However, the lysates also contain a
      large excess of infectious phage particles which complicate use of the packaged
      cosmids. I report that cosmids packaged by induction of a strain carrying a
      prophage with an altered cos region results in lysates containing very high
      levels (>10(10)/ml) of particles that contain cosmid DNA together with very few
      infectious phage particles. These lysates can be used to transduce cosmid DNA
      into all of the cells of a growing culture with minimal physiological
      disturbance. When the cosmid carries a conditionally active origin of
      replication, transductional introduction of the cosmid under nonreplicative
      conditions provides a system of transient expression. Transient expression has
      been used to make a recA strain temporarily recombination proficient and to
      temporarily introduce a site-specific recombinase. Transductional introduction of
      a cosmid also allows absolute off-to-on transcriptional control of nonessential
      genes. Two examples are given showing that when a strain carrying a null mutation
      in the gene of interest is transduced with a packaged cosmid carrying a
      functional copy of that gene, the expression of the gene rapidly goes from
      absolutely off to high-level expression. Additional possible uses of in vivo
      packaged cosmids are proposed.

PMID- 14594825
TI  - Null mutations in a Nudix gene, ygdP, implicate an alarmone response in a novel
      suppression of hybrid jamming.
AB  - Induction of the toxic LamB-LacZ protein fusion, Hyb42-1, leads to a lethal
      generalized protein export defect. The prlF1 suppressor causes hyperactivation of
      the cytoplasmic Lon protease and relieves the inducer sensitivity of Hyb42-1.
      Since prlF1 does not cause a detectable change in the stability or level of the
      hybrid protein, we conducted a suppressor screen, seeking factors genetically
      downstream of lon with prlF1-like phenotypes. Two independent insertions in the
      ygdP open reading frame relieve the toxicity of the fusion protein and share two
      additional properties with prlF1: cold sensitivity and the ability to suppress
      the temperature sensitivity of a degP null mutation. Despite these similarities,
      ygdP does not appear to act in the same genetic pathway as prlF1 and lon,
      suggesting a fundamental link between the phenotypes. We speculate that the
      common properties of the suppressors relate to secretion defects. The ygdP gene
      (also known as nudH) has been shown to encode a Nudix protein that acts as a
      dinucleotide oligophosphate (alarmone) hydrolase. Our results suggest that loss
      of ygdP function leads to the induction of an alarmone-mediated response that
      affects secretion. Using an epitope-tagged ygdP construct, we present evidence
      that this response is sensitive to secretion-related stress and is regulated by
      differential proteolysis of YgdP in a self-limiting manner.

PMID- 14594826
TI  - Assembly of TolC, a structurally unique and multifunctional outer membrane
      protein of Escherichia coli K-12.
AB  - TolC is a multifunctional outer membrane protein of Escherichia coli that folds
      into a novel alpha-beta-barrel conformation absent in the other model outer
      membrane proteins used in assembly studies. The data presented in this work show
      that the unique folded structure of TolC reflects a unique assembly pathway.
      During its assembly, the newly translocated nascent TolC monomers are released in
      the periplasm. Maturation of these nascent monomers, and possibly their
      oligomerization, in the periplasm precedes their insertion in the outer membrane.
      The completion of the assembly process is signaled by the development of a
      characteristic proteinase K-resistant fragment generated by cleavage at a single,
      periplasmically exposed, protease-sensitive site of the membrane-anchored trimer.
      None of the assembly steps of TolC is affected by known folding factors, such as
      SurA, Skp, and lipopolysaccharide, which have profound effects on the assembly of
      other model trimeric outer membrane proteins. Two assembly-defective TolC mutants
      were isolated and characterized. One of the mutants (TolC(I106N)) was defective
      in the folding of nascent monomers, while the other (TolC(S350F)) was impaired in
      steps involving trimerization and membrane insertion of folded monomers.

PMID- 14594827
TI  - Identification and characterization of a unique adenosine kinase from
      Mycobacterium tuberculosis.
AB  - Adenosine kinase (AK) is a purine salvage enzyme that catalyzes the
      phosphorylation of adenosine to AMP. In Mycobacterium tuberculosis, AK can also
      catalyze the phosphorylation of the adenosine analog 2-methyladenosine (methyl
      Ado), the first step in the metabolism of this compound to an active form.
      Purification of AK from M. tuberculosis yielded a 35-kDa protein that existed as
      a dimer in its native form. Adenosine (Ado) was preferred as a substrate at least
      30-fold (Km = 0.8 +/- 0.08 microM) over other natural nucleosides, and substrate
      inhibition was observed when Ado concentrations exceeded 5 micro M. M.
      tuberculosis and human AKs exhibited different affinities for methyl-Ado, with Km
      values of 79 and 960 microM, respectively, indicating that differences exist
      between the substrate binding sites of these enzymes. ATP was a good phosphate
      donor (Km = 1100 +/- 140 microM); however, the activity levels observed with dGTP
      and GTP were 4.7 and 2.5 times the levels observed with ATP, respectively. M.
      tuberculosis AK activity was dependent on Mg2+, and activity was stimulated by
      potassium, as reflected by a decrease in the Km and an increase in Vmax for both
      Ado and methyl-Ado. The N-terminal amino acid sequence of the purified enzyme
      revealed complete identity with Rv2202c, a protein currently classified as a
      hypothetical sugar kinase. When an AK-deficient strain of M. tuberculosis
      (SRICK1) was transformed with this gene, it exhibited a 5,000-fold increase in AK
      activity compared to extracts from the original mutants. These results verified
      that the protein that we identified as AK was coded for by Rv2202c. AK is not
      commonly found in bacteria, and to the best of our knowledge, M. tuberculosis AK
      is the first bacterial AK to be characterized. The enzyme shows greater sequence
      homology with ribokinase and fructokinase than it does with other AKs. The
      multiple differences that exist between M. tuberculosis and human AKs may provide
      the molecular basis for the development of nucleoside analog compounds with
      selective activity against M. tuberculosis.

PMID- 14594829
TI  - CTP limitation increases expression of CTP synthase in Lactococcus lactis.
AB  - CTP synthase is encoded by the pyrG gene and catalyzes the conversion of UTP to
      CTP. A Lactococcus lactis pyrG mutant with a cytidine requirement was
      constructed, in which beta-galactosidase activity in a pyrG-lacLM transcriptional
      fusion was used to monitor gene expression of pyrG. A 10-fold decrease in the CTP
      pool induced by cytidine limitation was found to immediately increase expression
      of the L. lactis pyrG gene. The final level of expression of pyrG is 37-fold
      higher than the uninduced level. CTP limitation has pronounced effects on central
      cellular metabolism, and both RNA and protein syntheses are inhibited. Expression
      of pyrG responds only to the cellular level of CTP, since expression of pyrG has
      no correlation to alterations in UTP, GTP, and ATP pool sizes. In the
      untranslated pyrG leader sequence a potential terminator structure can be
      identified, and this structure is required for regulation of the pyrG gene. It is
      possible to fold the pyrG leader in an alternative structure that would prevent
      the formation of the terminator. We suggest a model for pyrG regulation in L.
      lactis, and probably in other gram-positive bacteria as well, in which pyrG
      expression is directly dependent on the CTP concentration through an attenuator
      mechanism. At normal CTP concentrations a terminator is preferentially formed in
      the pyrG leader, thereby reducing expression of CTP synthase. At low CTP
      concentrations the RNA polymerase pauses at a stretch of C residues in the pyrG
      leader, thereby allowing an antiterminator to form and transcription to proceed.
      This model therefore does not include any trans-acting protein for sensing the
      CTP concentration as previously proposed for Bacillus subtilis.

PMID- 14594828
TI  - Arginine-agmatine antiporter in extreme acid resistance in Escherichia coli.
AB  - The process of arginine-dependent extreme acid resistance (XAR) is one of several
      decarboxylase-antiporter systems that protects Escherichia coli and possibly
      other enteric bacteria from exposure to the strong acid environment of the
      stomach. Arginine-dependent acid resistance depends on an intracellular proton
      utilizing arginine alpha-decarboxylase and a membrane transport protein necessary
      for delivering arginine to and removing agmatine, its decarboxylation product,
      from the cytoplasm. The arginine system afforded significant protection to wild
      type E. coli cells in our acid shock experiments. The gene coding for the
      transport protein is identified here as a putative membrane protein of unknown
      function, YjdE, which we now name adiC. Strains from which this gene is deleted
      fail to mount arginine-dependent XAR, and they cannot perform coupled transport
      of arginine and agmatine. Homologues of this gene are found in other bacteria in
      close proximity to homologues of the arginine decarboxylase in a gene arrangement
      pattern similar to that in E coli. Evidence for a lysine-dependent XAR system in
      E. coli is also presented. The protection by lysine, however, is milder than that
      by arginine.

PMID- 14594830
TI  - Identification and characterization of a pSLA2 plasmid locus required for linear
      DNA replication and circular plasmid stable inheritance in Streptomyces lividans.
AB  - Streptomyces linear plasmids and linear chromosomes can replicate also in a
      circular form when their telomeres are deleted. The 17-kb linear plasmid pSLA2
      has been a useful model in studies of such replicons. Here we report that the
      minimal origin initiating replication of pSLA2-derived plasmids as circular
      molecules cannot propagate these plasmids in a linear mode unless they also
      contain a novel plasmid-encoded locus, here named rlrA (required for linear
      replication). In contrast with the need for rlrA to accomplish replication of
      telomere-containing linear plasmids, expression of rlrA, which encodes two LuxR
      family regulatory domains, interferes with the establishment of pSLA2 in circular
      form in Streptomyces lividans transformants. The additional presence of an
      adjacent divergently transcribed locus, rorA (rlrA override), which strongly
      resembles the kor (kil override) transcription control genes identified
      previously on Streptomyces plasmids, reversed the detrimental effects of rlrA on
      plasmid establishment and additionally stabilized circular plasmid inheritance by
      spores during the S. lividans life cycle. While the effects of the rlrA/rorA
      locus of pSLA2 were seen also on linear plasmids derived from the unrelated SLP2
      replicon, they did not extend to plasmids whose replication was initiated at a
      cloned chromosomal origin. Our results establish the existence of, and provide
      the initial description of, a novel plasmid-borne regulatory system that
      differentially affects the propagation of linear and circular plasmids in
      Streptomyces.

PMID- 14594831
TI  - The ADP-ribosylating toxin, AexT, from Aeromonas salmonicida subsp. salmonicida
      is translocated via a type III secretion pathway.
AB  - AexT is an extracellular ADP ribosyltransferase produced by the fish pathogen
      Aeromonas salmonicida subsp. salmonicida. The protein is secreted by the
      bacterium via a recently identified type III secretion system. In this study, we
      have identified a further 12 open reading frames that possess high homology to
      genes encoding both structural and regulatory components of the Yersinia type III
      secretion apparatus. Using marker replacement mutagenesis of aopB, the A.
      salmonicida subsp. salmonicida homologue of yopB in Yersinia, we demonstrate that
      the bacterium translocates the AexT toxin directly into the cytosol of cultured
      fish cells via this type III secretion pathway. An acrV mutant of A. salmonicida
      subsp. salmonicida displays a calcium-blind phenotype, expressing and secreting
      significant amounts of AexT even in the presence of CaCl2 concentrations as high
      as 10 mM. This acrV mutant is also unable to translocate AexT into the cytosol of
      fish cells, indicating AcrV is involved in the translocation process.
      Inactivation of either the aopB or acrV gene in A. salmonicida subsp. salmonicida
      (resulting in an inability to translocate AexT) is accompanied by a loss of
      cytotoxicity that can be restored by trans complementation. Finally, we present
      data indicating that preincubation of the wild-type bacteria with antibodies
      directed against recombinant AcrV-His protein provides fish cells protection
      against the toxic effects of the bacterium.

PMID- 14594832
TI  - MtaR, a regulator of methionine transport, is critical for survival of group B
      streptococcus in vivo.
AB  - The group B streptococcus (GBS) is an important human pathogen that infects
      newborns as well as adults. GBS also provides a model system for studying
      adaptation to different host environments due to its ability to survive in a
      variety of sites within the host. In this study, we have characterized a
      transcription factor, MtaR, that is essential for the ability of GBS to survive
      in vivo. An isogenic strain bearing a kanamycin insertion in mtaR was attenuated
      for survival in a neonatal-rat model of sepsis. The mtaR mutant grew poorly in
      human plasma, suggesting that its utilization of plasma-derived nutrients was
      inefficient. When an excess of exogenous methionine (200 microg/ml) was provided
      to the mtaR mutant, its growth rate in plasma was restored to that of the wild
      type strain. The mtaR mutant grew poorly in chemically defined medium (CDM)
      prepared with methionine at a concentration similar to that of plasma (4
      microg/ml) but was able to grow normally in CDM prepared with a high
      concentration of methionine (400 microg/ml). Both the wild-type strain and the
      mtaR mutant were incapable of growth in CDM lacking methionine, indicating that
      GBS cannot synthesize methionine de novo. When the abilities of the strains to
      incorporate radiolabeled methionine were compared, the mtaR mutant incorporated
      fivefold less methionine than the wild-type strain during a 10-min period.
      Collectively, the results from this study suggest that the ability to regulate
      expression of a methionine transport system is critical for GBS survival in vivo.

PMID- 14594833
TI  - A novel family of Escherichia coli toxin-antitoxin gene pairs.
AB  - Bacterial toxin-antitoxin protein pairs (TA pairs) encode a toxin protein, which
      poisons cells by binding and inhibiting an essential enzyme, and an antitoxin
      protein, which binds the toxin and restores viability. We took an approach that
      did not rely on sequence homology to search for unidentified TA pairs in the
      genome of Escherichia coli K-12. Of 32 candidate genes tested, ectopic expression
      of 6 caused growth inhibition. In this report, we focus on the initial
      characterization of yeeV, ykfI, and ypjF, a novel family of toxin proteins.
      Coexpression of the gene upstream of each toxin restored the growth rate to that
      of the uninduced strain. Unexpectedly, we could not detect in vivo protein
      protein interactions between the new toxin and antitoxin pairs. Instead, the
      antitoxins appeared to function by causing a large reduction in the level of
      cellular toxin protein.

PMID- 14594834
TI  - Temperature sensing by the dsrA promoter.
AB  - Synthesis of the small regulatory RNA DsrA is under temperature control. The
      minimal dsrA promoter of 36 bp contains sufficient information to ensure such
      regulation. In vivo, we have analyzed the critical elements responsible for the
      temperature control of dsrA by using a collection of chimeric promoters combining
      various elements of the dsrA promoter and the lacUV5 promoter, which does not
      respond to temperature. Our results favor an RNA polymerase-DNA interaction model
      instead of a trans-acting factor for temperature regulation. While all of the
      elements of the dsrA promoter contribute to temperature-sensitive expression, the
      sequence of the -10 box and the spacer region are the essential elements for the
      thermal response of the dsrA promoter. The proper context for these promoter
      elements, including at least one of the flanking elements, the -35 region or the
      start site region, is also required. Point mutations demonstrate that the
      sequence of the -10 box imposes constraints on the length and the sequence of the
      spacer and/or its AT richness, even at low temperature. These results show a
      complex interdependence of different regions in the promoter for temperature
      regulation.

PMID- 14594835
TI  - Slr2013 is a novel protein regulating functional assembly of photosystem II in
      Synechocystis sp. strain PCC 6803.
AB  - The Synechocystis sp. strain PCC 6803, which has a T192H mutation in the D2
      protein of photosystem II, is an obligate photoheterotroph due to the lack of
      assembled photosystem II complexes. A secondary mutant, Rg2, has been selected
      that retains the T192H mutation but is able to grow photoautotrophically.
      Restoration of photoautotrophic growth in this mutant was caused by early
      termination at position 294 in the Slr2013 protein. The T192H mutant with
      truncated Slr2013 forms fully functional photosystem II reaction centers that
      differ from wild-type reaction centers only by a 30% higher rate of charge
      recombination between the primary electron acceptor, QA-, and the donor side and
      by a reduced stability of the oxidized form of the redox-active Tyr residue, YD,
      in the D2 protein. This suggests that the T192H mutation itself did not directly
      affect electron transfer components, but rather affected protein folding and/or
      stable assembly of photosystem II, and that Slr2013 is involved in the folding of
      the D2 protein and the assembly of photosystem II. Besides participation in
      photosystem II assembly, Slr2013 plays a critical role in the cell, because the
      corresponding gene cannot be deleted completely under conditions in which
      photosystem II is dispensable. Truncation of Slr2013 by itself does not affect
      photosynthetic activity of Synechocystis sp. strain PCC 6803. Slr2013 is
      annotated in CyanoBase as a hypothetical protein and shares a DUF58 family
      signature with other hypothetical proteins of unknown function. Genes for close
      homologues of Slr2013 are found in other cyanobacteria (Nostoc punctiforme,
      Anabaena sp. strain PCC 7120, and Thermosynechococcus elongatus BP-1), and
      apparent orthologs of this protein are found in Eubacteria and Archaea, but not
      in eukaryotes. We suggest that Slr2013 regulates functional assembly of
      photosystem II and has at least one other important function in the cell.

PMID- 14594836
TI  - SoxRS-regulated expression and genetic analysis of the yggX gene of Escherichia
      coli.
AB  - Genomic studies with bacteria have identified redox-responsive genes without
      known roles in counteracting oxidative damage. Previous transcriptional profiling
      showed that expression of one such gene, yggX, was activated by superoxide stress
      in Escherichia coli. Here we show that this activation could be mimicked by
      artificial expression of the regulatory protein SoxS. Northern analysis confirmed
      the transcriptional activation of yggX by oxidative stress or SoxS expression but
      not in response to the related MarA or Rob proteins. Northern analysis showed
      that mltC, which codes for a peptidoglycan hydrolase and is positioned
      immediately downstream of yggX, was also regulated by oxidative stress or ectopic
      expression of SoxS. Purified SoxS protein bound to the predicted yggX promoter
      region, between positions 223 and 163 upstream from the yggX translational start
      site. Within this region, a 20-bp sequence was found to be necessary for
      oxidative stress-mediated activation of yggX transcription. A yggX deletion
      strain was hypersensitive to the redox-cycling agent paraquat, and a plasmid
      expressing YggX complemented the sensitivity of the deletion strain. Under
      exposure to paraquat, the yggX deletion strain showed a deficiency in aconitase
      activity compared to the isogenic wild-type strain, while expression of YggX from
      a multicopy plasmid increased the aconitase levels above those of the wild-type
      strain. These results demonstrate the direct regulation of the yggX gene by the
      redox-sensing SoxRS system and provide further evidence for the involvement of
      yggX in protection of iron-sulfur proteins against oxidative damage.

PMID- 14594837
TI  - Purification and characterization of the PcrA helicase of Bacillus anthracis.
AB  - PcrA is an essential helicase in gram-positive bacteria, and a gene encoding this
      helicase has been identified in all such organisms whose genomes have been
      sequenced so far. The precise role of PcrA that makes it essential for cell
      growth is not known; however, PcrA does not appear to be necessary for chromosome
      replication. The pcrA gene was identified in the genome of Bacillus anthracis on
      the basis of its sequence homology to the corresponding genes of Bacillus
      subtilis and Staphylococcus aureus, with which it shares 76 and 72% similarity,
      respectively. The pcrA gene of B. anthracis was isolated by PCR amplification and
      cloning into Escherichia coli. The PcrA protein was overexpressed with a His6
      fusion at its amino-terminal end. The purified His-PcrA protein showed ATPase
      activity that was stimulated in the presence of single-stranded (ss) DNA (ssDNA).
      Interestingly, PcrA showed robust 3'-->5' as well as 5'-->3' helicase activities,
      with substrates containing a duplex region and a 3' or 5' ss poly(dT) tail. PcrA
      also efficiently unwound oligonucleotides containing a duplex region and a 5' or
      3' ss tail with the potential to form a secondary structure. DNA binding
      experiments showed that PcrA bound much more efficiently to oligonucleotides
      containing a duplex region and a 5' or 3' ss tail with a potential to form a
      secondary structure than to those with ssDNAs or duplex DNAs with ss poly(dT)
      tails. Our results suggest that specialized DNA structures and/or sequences
      represent natural substrates of PcrA in biochemical processes that are essential
      for the growth and survival of gram-positive organisms, including B. anthracis.

PMID- 14594838
TI  - MgrA, an orthologue of Mga, Acts as a transcriptional repressor of the genes
      within the rlrA pathogenicity islet in Streptococcus pneumoniae.
AB  - Streptococcus pneumoniae normally resides in the human nasopharynx in a
      nondisease state. In response to unknown triggers this organism can descend to
      the lower respiratory tract and/or invade the bloodstream. Regulation and
      activation of virulence genes play essential roles in this process of disease
      development. Characterization of S. pneumoniae regulatory networks has been a
      recent area of interest, but despite inroads little is known about regulation of
      virulence genes in this pathogen. A putative transcriptional regulator in S.
      pneumoniae, mgrA, which exhibits homology to the virulence gene activator mga of
      group A streptococcus, was previously identified as a regulator that is required
      for development of pneumonia in a murine model. In this study we confirmed that
      mgrA plays a role in both nasopharyngeal carriage and pneumonia. Transcriptional
      profiling by microarray technology was used to show that mgrA acts as a repressor
      of the previously characterized rlrA pathogenicity islet. This is manifested
      phenotypically by a decrease in adherence to epithelial cells in tissue culture
      since the rlrA pathogenicity islet contains genes mediating adherence.

PMID- 14594839
TI  - Flavobacterium johnsoniae GldH is a lipoprotein that is required for gliding
      motility and chitin utilization.
AB  - Cells of Flavobacterium johnsoniae move rapidly over surfaces by gliding
      motility. The mechanism of this form of motility is not known. Six genes (gldA,
      gldB, gldD, gldF, gldG, and ftsX) that are required for gliding have been
      described. Tn4351 mutagenesis was used to identify another gene, gldH, which is
      required for cell movement. GldH mutants formed nonspreading colonies, and
      individual cells lacked the cell movements and ability to propel latex spheres
      along their surfaces that are characteristic of wild-type cells. gldH mutants
      also failed to digest chitin and were resistant to bacteriophages that infect
      wild-type cells. Introduction of pMM293, which carries wild-type gldH, restored
      to the gldH mutants colony spreading, cell motility, the ability to move latex
      spheres, phage sensitivity, and the ability to digest chitin. gldH encodes a
      predicted 141-amino-acid protein that localized to the membrane fraction.
      Labeling studies with [3H]palmitate demonstrated that GldH is a lipoprotein. GldB
      and GldD, which were previously described, also appear to be lipoproteins. GldH
      does not exhibit significant amino acid similarity to proteins of known function
      in the databases. Putative homologs of gldH of unknown function are found in
      motile (Cytophaga hutchinsonii) and apparently nonmotile (Bacteroides
      thetaiotaomicron, Bacteroides fragilis, Tannerella forsythensis, Porphyromonas
      gingivalis, and Prevotella intermedia) members of the Cytophaga-Flavobacterium
      Bacteroides group.

PMID- 14594840
TI  - Flagellin glycosylation island in Pseudomonas syringae pv. glycinea and its role
      in host specificity.
AB  - The deduced amino acid sequences of the flagellins of Pseudomonas syringae pv.
      tabaci and P. syringae pv. glycinea are identical; however, their abilities to
      induce a hypersensitive reaction are clearly different. The reason for the
      difference seems to depend on the posttranslational modification of the
      flagellins. To investigate the role of this posttranslational modification in the
      interactions between plants and bacterial pathogens, we isolated genes that are
      potentially involved in the posttranslational modification of flagellin in P.
      syringae pv. glycinea (glycosylation island); then defective mutants with
      mutations in these genes were generated. There are three open reading frames in
      the glycosylation island, designated orf1, orf2, and orf3. orf1 and orf2 encode
      putative glycosyltransferases, and mutants with defects in these open reading
      frames, deltaorf1 and deltaorf2, secreted nonglycosylated and slightly
      glycosylated flagellins, respectively. Inoculation tests performed with these
      mutants and original nonhost tobacco leaves revealed that deltaorf1 and deltaorf2
      could grow on tobacco leaves and caused symptom-like changes. In contrast, these
      mutants failed to cause symptoms on original host soybean leaves. These data
      indicate that putative glycosyltransferases encoded in the flagellin
      glycosylation island are strongly involved in recognition by plants and could be
      the specific determinants of compatibility between phytopathogenic bacteria and
      plant species.

PMID- 14594841
TI  - Localization of the vegetative cell wall hydrolases LytC, LytE, and LytF on the
      Bacillus subtilis cell surface and stability of these enzymes to cell wall-bound
      or extracellular proteases.
AB  - LytF, LytE, and LytC are vegetative cell wall hydrolases in Bacillus subtilis.
      Immunofluorescence microscopy showed that an epitope-tagged LytF fusion protein
      (LytF-3xFLAG) in the wild-type background strain was localized at cell separation
      sites and one of the cell poles of rod-shaped cells during vegetative growth.
      However, in a mutant lacking both the cell surface protease WprA and the
      extracellular protease Epr, the fusion protein was observed at both cell poles in
      addition to cell separation sites. This suggests that LytF is potentially
      localized at cell separation sites and both cell poles during vegetative growth
      and that WprA and Epr are involved in LytF degradation. The localization pattern
      of LytE-3xFLAG was very similar to that of LytF-3xFLAG during vegetative growth.
      However, especially in the early vegetative growth phase, there was a remarkable
      difference between the shape of cells expressing LytE-3xFLAG and the shape of
      cells expressing LytF-3xFLAG. In the case of LytF-3xFLAG, it seemed that the
      signals in normal rod-shaped cells were stronger than those in long-chain cells.
      In contrast, the reverse was found in the case of LytE-3xFLAG. This difference
      may reflect the dependence on different sigma factors for gene expression. The
      results support and extend the previous finding that LytF and LytE are cell
      separating enzymes. On the other hand, we observed that cells producing LytC
      3xFLAG are uniformly coated with the fusion protein after the middle of the
      exponential growth phase, which supports the suggestion that LytC is a major
      autolysin that is not associated with cell separation.

PMID- 14594843
TI  - Synthesis and deformylation of Staphylococcus aureus delta-toxin are linked to
      tricarboxylic acid cycle activity.
AB  - In bacteria, translation initiates with formyl-methionine; however, the N
      terminal formyl group is usually removed by peptide deformylase, an enzymatic
      activity requiring iron. Staphylococcus aureus delta-toxin is a 26-amino-acid
      polypeptide secreted predominantly with a formylated N-terminal methionine, which
      led us to investigate regulation of delta-toxin deformylation. We observed that
      during exponential and early postexponential growth, delta-toxin accumulated in
      the culture medium in formylated and deformylated forms. In contrast, only
      formylated delta-toxin accumulated after the early postexponential phase. The
      transition from producing both species of delta-toxin to producing only formyl
      methionine-containing delta-toxin coincided with increased tricarboxylic acid
      (TCA) cycle activity. The TCA cycle contains several iron-requiring enzymes,
      which led us to hypothesize that TCA cycle induction depletes the iron in the
      culture medium, thereby inhibiting peptide deformylase activity. As expected, S.
      aureus depletes the iron in the culture medium between the postexponential and
      stationary phases of growth. Inhibition of delta-toxin deformylation was relieved
      by TCA cycle inactivation or by addition of supplemental iron to the culture
      medium. Of interest, peptides containing formyl-methionine are potent
      chemoattractants for neutrophils, suggesting that delta-toxin deformylation may
      have functional consequences. We found neutrophil chemotactic activity only with
      formylated delta-toxin. The S. aureus TCA cycle is derepressed upon depletion of
      rapidly catabolizable carbon sources; this coincides with the transition to
      producing only formylated delta-toxin and results in an increased inflammatory
      response. The proinflammatory response should increase host cell damage and
      result in the release of nutrients. Taken together, these results establish that
      there is an important linkage between bacterial metabolism and pathogenesis.

PMID- 14594842
TI  - The product of a developmental gene, crgA, that coordinates reproductive growth
      in Streptomyces belongs to a novel family of small actinomycete-specific
      proteins.
AB  - On solid media, the reproductive growth of Streptomyces involves antibiotic
      biosynthesis coincident with the erection of filamentous aerial hyphae. Following
      cessation of growth of an aerial hypha, multiple septation occurs at the tip to
      form a chain of unigenomic spores. A gene, crgA, that coordinates several aspects
      of this reproductive growth is described. The gene product is representative of a
      well-conserved family of small actinomycete proteins with two C-terminal
      hydrophobic-potential membrane-spanning segments. In Streptomyces avermitilis,
      crgA is required for sporulation, and inactivation of the gene abolished most
      sporulation septation in aerial hyphae. Disruption of the orthologous gene in
      Streptomyces coelicolor indicates that whereas CrgA is not essential for
      sporulation in this species, during growth on glucose-containing media, it
      influences the timing of the onset of reproductive growth, with precocious
      erection of aerial hyphae and antibiotic production by the mutant. Moreover, CrgA
      subsequently acts to inhibit sporulation septation prior to growth arrest of
      aerial hyphae. Overexpression of CrgA in S. coelicolor, uncoupling any
      nutritional and growth phase-dependent regulation, results in growth of
      nonseptated aerial hyphae on all media tested, consistent with a role for the
      protein in inhibiting sporulation septation.

PMID- 14594845
TI  - Starvation survival response of Mycobacterium tuberculosis.
AB  - The ability of Mycobacterium tuberculosis auxotrophs to survive long-term
      starvation was measured. Tryptophan and histidine auxotrophs did not survive
      single-amino-acid starvation, whereas a proline auxotroph did. All three
      auxotrophs survived complete starvation. THP-1 cells were also able to restrict
      the growth of the tryptophan and histidine auxotrophs.

PMID- 14594844
TI  - Structural and topographical studies of the type IV bundle-forming pilus assembly
      complex of enteropathogenic Escherichia coli.
AB  - The type IV bundle-forming pili (BFP) of enteropathogenic Escherichia coli (EPEC)
      are required for virulence in orally challenged human volunteers and for the
      localized adherence and autoaggregation in vitro phenotypes. BFP filament
      biogenesis and function are encoded by the 14-gene bfp operon. The BFP assembly
      complex, containing a BfpB-His6 fusion protein, was chemically cross-linked in
      situ, and the complex was then purified from BFP-expressing EPEC by a combination
      of nickel- and BfpB antibody-based affinity chromatography. Characterization of
      the isolated complex by immunoblotting using BFP protein-specific antibodies
      showed that at least 10 of the 14 proteins specified by the bfp operon physically
      interact to form an oligomeric complex. Proteins localized to the outer membrane,
      inner membrane, and periplasm are within this complex, thus demonstrating that
      the complex spans the periplasmic space. A combination of immunofluorescence and
      immuno-gold thin-section transmission electron microscopy studies localized this
      complex to one pole of the cell.

PMID- 14594846
TI  - Secretion defects that activate the phage shock response of Escherichia coli.
AB  - The phage shock protein (psp) operon of Escherichia coli is induced by membrane
      damaging cues. Earlier studies linked defects in secretion across the inner
      membrane to induction of the psp response. Here we show that defects in yidC and
      sec secretion induce psp but that defects in tat and srp have no effect. We have
      also determined the cellular location of PspB and PspD proteins.

PMID- 14594847
TI  - Virulence conversion of Legionella pneumophila by conjugal transfer of
      chromosomal DNA.
AB  - In this study, we examined whether virulence conversion occurs in Legionella
      pneumophila by conjugal transfer of chromosomal DNA. A virulent strain, K6, which
      has the genes for Kmr and LacZ+ transposed in the chromosome of strain
      Philadelphia-1, which belongs to serogroup 1, was used as one parent, and an
      avirulent strain, Chicago-2S, which is a spontaneous streptomycin-resistant
      derivative of strain Chicago-2 belonging to serogroup 6, was used as the other
      parent. Experiments in which K6 (approximately 2.6 x 10(9) CFU) and Chicago-2S
      (approximately 8.9 x 10(9) CFU) were mated typically yielded 10(3) Kmr Smr LacZ+
      transconjugants. Thirty-two (about 2.8%) of 1,152 transconjugants belonging to
      serogroup 6 acquired the ability to grow intracellularly in Acanthamoeba
      castellanii and guinea pig macrophages. When guinea pigs were infected with
      sublethal doses of Legionella aerosols generated from one of these
      transconjugants (HM1011), they developed a severe pneumonia similar to that
      caused by donor strain K6. These results show that avirulent strain Chicago-2S
      changed into virulent strain HM1011 through conjugation with virulent strain K6.
      Furthermore, we showed that Legionella chromosomal virulence genes (icm-dot
      locus) were horizontally transferred by the conjugation system. The chromosomal
      conjugation system may play a role(s) in the evolution of L. pneumophila.

PMID- 14594848
TI  - Translocon "pulling" of nascent SecM controls the duration of its translational
      pause and secretion-responsive secA regulation.
AB  - SecA is an ATPase and motor protein that drives protein translocation across the
      bacterial plasma membrane. In Escherichia coli SecA levels are regulated by the
      secretion needs of the cell utilizing secM, which encodes a secreted protein.
      Previous studies demonstrated that this regulation requires a translational pause
      within secM, whose duration regulates the accessibility of the secA Shine
      Dalgarno sequence on secM secA mRNA. Here we provide evidence that translocon
      "pulling" of nascent SecM is what regulates the duration of the secM
      translational pause, and thus secA expression levels, thereby providing direct
      support for this model.

PMID- 14594850
TI  - In vivo effect of mutations at the PRPP binding site of the Bacillus subtilis
      purine repressor.
AB  - The Bacillus subtilis PurR mediates adenine repression and guanosine induction of
      purA. PRPP inhibits binding of PurR to DNA in vitro. Mutations in the PRPP
      binding motif of PurR caused strong repression regardless of purine exclusions or
      additions, establishing the role of PRPP as regulator of PurR.

PMID- 14594849
TI  - aadA confers streptomycin resistance in Borrelia burgdorferi.
AB  - To enhance genetic manipulation of the Lyme disease spirochete Borrelia
      burgdorferi, we assayed the aadA gene for the ability to confer resistance to the
      antibiotics spectinomycin and streptomycin. Using the previously described pBSV2
      as a backbone, a shuttle vector, termed pKFSS1, which carries the aadA open
      reading frame fused to the B. burgdorferi flgB promoter was constructed. The
      hybrid flgB promoter-aadA cassette confers resistance to spectinomycin and
      streptomycin in both B. burgdorferi and Escherichia coli. pKFSS1 has a
      replication origin derived from the 9-kb circular plasmid and can be comaintained
      in B. burgdorferi with extant shuttle vector pCE320, which has a replication
      origin derived from a 32-kb circular plasmid, or pBSV2, despite the fact that
      pKFSS1 and pBSV2 have the same replication origin. Our results demonstrate the
      availability of a new selectable marker and shuttle vector for genetically
      dissecting B. burgdorferi at the molecular level.

PMID- 14594851
TI  - A mutation in the essential gene gmk (encoding guanlyate kinase) generates a
      requirement for adenine at low temperature in Salmonella enterica.
AB  - In Salmonella enterica serovar Typhimurium, gmk encodes guanylate kinase, an
      essential enzyme involved in the synthesis and salvage of guanine nucleotides.
      Here we report the isolation of a mutation in gmk that results in a nutritional
      requirement for adenine at low temperature. Comparisons of kinetic parameters
      from the wild-type and mutant Gmk enzymes revealed that the mutant enzyme had a
      more than 20-fold-higher Km for ATP than the wild-type enzyme. The growth
      dependence of the mutant on temperature and/or adenine could not be explained as
      a direct result of this kinetic difference. We propose a model in which
      previously described regulatory effects of GMP are responsible for these
      phenotypes.

PMID- 14594852
TI  - Mycothiol is essential for growth of Mycobacterium tuberculosis Erdman.
AB  - Mycothiol (MSH) is the major low-molecular-mass thiol in mycobacteria and is
      associated with the protection of Mycobacterium tuberculosis from toxic oxidants
      and antibiotics. The biosynthesis of MSH is a multistep process, with the
      enzymatic reaction designated MshC being the ligase step in MSH production. A
      targeted disruption of the native mshC gene in M. tuberculosis Erdman produced no
      viable clones possessing either a disrupted mshC gene or reduced levels of MSH.
      However, when a second copy of the mshC gene was incorporated into the chromosome
      prior to the targeted disruption, multiple clones having the native gene
      disrupted and the second copy of mshC intact were obtained. These clones produced
      normal levels of MSH. These results demonstrate that the mshC gene and, more
      generally, the production of MSH are essential for the growth of M. tuberculosis
      Erdman under laboratory conditions.

PMID- 14594853
TI  - Structure of haloacetate-catabolic IncP-1beta plasmid pUO1 and genetic mobility
      of its residing haloacetate-catabolic transposon.
AB  - The self-transmissible plasmid pUO1 from Delftia acidovorans strain B carries two
      haloacetate-catabolic transposons, TnHad1 and TnHad2, and the mer genes for
      resistance to mercury. The complete 67,066-bp sequence of pUO1 revealed that the
      mer genes were also carried by two Tn402/Tn5053-like transposons, Tn4671 and
      Tn4672, and that the pUO1 backbone regions shared 99% identity to those of the
      archetype IncP-1beta plasmid R751. Comparison of pUO1 with three other IncP-1beta
      plasmids illustrated the importance of transposon insertion in the diversity and
      evolution of this group of plasmids. Mutational analysis of the four outermost
      residues in the inverted repeats (IRs) of TnHad2, a Tn21-related transposon,
      revealed a crucial role of the second residue of its IRs in transposition.

PMID- 14594854
TI  - Canine trachealis muscle shortening and cartilage mechanics.
AB  - Canine trachealis muscle will shorten by 70% of resting length when maximally
      stimulated in vitro. In contrast, trachealis muscle will shorten by only 30-40%
      when stimulated in vivo. To examine the possibility that an elastic load applied
      by the tracheal cartilage contributes to the in vivo limitation of shortening,
      single pairs of sonomicrometry crystals were inserted into the trachealis muscle
      at the level of the fifth cartilage ring in five dogs. The segment containing the
      crystals was then excised and mounted on a tension-testing apparatus. Points on
      the active length-tension curve and the passive length-tension relation of the
      cartilage only were determined. The preload applied to the muscle before
      contraction varied from 10 to 40 g (mean 21 +/- 4 g). The afterload applied by
      the cartilage during trachealis contraction ranged from 13 to 56 g (30 +/- 6 g).
      The calculated elastic afterloads were substantial and appeared to be sufficient
      to explain the degree of shortening observed in four of the seven rings; in the
      remaining three rings, the limitation of shortening was greater than would be
      expected from the elastic load provided by the cartilage. Additional sources of
      loading and/or additional mechanisms may contribute to limited in situ
      shortening. In summary, tracheal cartilage applies a preload and an elastic
      afterload to the trachealis that are substantial and contribute to the limitation
      of trachealis muscle shortening in vivo.

PMID- 14594855
TI  - Effects of postural changes and vestibular lesions on genioglossal muscle
      activity in conscious cats.
AB  - Previous studies in humans showed that genioglossal muscle activity is higher
      when individuals are supine than when they are upright, and prior experiments in
      anesthetized or decerebrate animals suggested that vestibular inputs might
      participate in triggering these alterations in muscle firing. The present study
      determined the effects of whole body tilts in the pitch (nose-up) plane on
      genioglossal activity in a conscious feline model and compared these responses
      with those generated by roll (ear-down) tilts. We also ascertained the effects of
      a bilateral vestibular neurectomy on the alterations in genioglossal activity
      elicited by changes in body position. Both pitch and roll body tilts produced
      modifications in muscle firing that were dependent on the amplitude of the
      rotation; however, the relative effects of ear-down and nose-up tilts on
      genioglossal activity were variable from animal to animal. The response
      variability observed might reflect the fact that genioglossus has a complex
      organization and participates in a variety of tongue movements; in each animal,
      electromyographic recordings presumably sampled the firing of different
      proportions of fibers in the various compartments and subcompartments of the
      muscle. Furthermore, removal of labyrinthine inputs resulted in alterations in
      genioglossal responses to postural changes that persisted until recordings were
      discontinued approximately 1 mo later, demonstrating that the vestibular system
      participates in regulating the muscle's activity. Peripheral vestibular lesions
      were subsequently demonstrated to be complete through the postmortem inspection
      of temporal bone sections or by observing that vestibular nucleus neurons did not
      respond to rotations in vertical planes.

PMID- 14594856
TI  - An age-related shift in the force-frequency relationship affects quadriceps
      fatigability in old adults.
AB  - We examined the effect of an age-related leftward shift in the force-frequency
      relationship on the comparative quadriceps fatigability of nine young (27 +/- 1
      yr old) and nine old men (78 +/- 1 yr old) during low-frequency electrical
      stimulation. Two different protocols of intermittent trains (6 pulses on, 650 ms
      off) of electrical stimulation at 25% maximum voluntary contraction were
      performed by both groups: 1) 180 trains at 14.3 Hz [constant frequency (CF)
      protocol], and 2) 180 trains at the frequency corresponding to 60% of each
      subject's force-frequency curve [normalized frequency (NF) protocol; young 14.9
      +/- 0.4 vs. old 12.7 +/- 0.5 Hz; P < 0.05]. The quadriceps of the old men were
      weaker (approximately 31%) and relaxation was slower compared with the young men,
      as assessed by the maximal relaxation rate constant of the 50-Hz tetanus (young
      12.1 +/- 0.2 vs. old 9.2 +/- 0.5 s(-1); P < 0.05) and a leftward shift in the
      force-frequency relationship. The NF protocol revealed a decreased fatigability
      in the quadriceps with old age (percentage of 1st contraction force remaining at
      180th: old 63.4 +/- 1.5 vs. young 58.2 +/- 1.7%; P < 0.05) that was masked during
      the CF protocol (old 60.7 +/- 1.6 vs. young 58.6 +/- 2.3%; P > 0.05).
      Irrespective of the protocol, the maximal relaxation rate was reduced to
      approximately 73 and approximately 57% of the prefatigue value in the young and
      old men, respectively. The age-related leftward shift in the force-frequency
      relationship of the quadriceps contributed to an underestimation of the fatigue
      resistance with old age during the CF protocol. However, when the stimulation
      frequency used in the NF protocol was adjusted to account for the age-related
      shift in the force-frequency relationship, the quadriceps muscles of the old men
      were less fatigable than those of the young men. Thus we suggest that whole
      muscle fatigability is better examined by electrical stimulation protocols that
      are adjusted for inter- and intragroup differences in the force-frequency
      relationship.

PMID- 14594857
TI  - Effects of different dropping intensities on fascicle and tendinous tissue
      behavior during stretch-shortening cycle exercise.
AB  - This study examined whether the elasticity of the tendinous tissues plays an
      important role in human locomotion by improving the power output and efficiency
      of skeletal muscle. Ten subjects performed one-leg drop jumps (DJ) from different
      dropping heights with a constant rebound height. The fascicle length of the
      vastus lateralis muscle was measured by using real-time ultrasonography during
      DJ. In the braking phase of the DJ, fascicle lengthening decreased and the
      tendinous tissue lengthening increased with increased dropping intensity. In the
      subsequent push-off phase, the shortening of tendinous tissues increased with
      higher dropping intensity. The averaged electromyographic activities of the
      preactivation and braking phases increased and those of the push-off phase
      decreased as the drop height was increased. With higher dropping height but
      constant submaximal rebound jump, the stretched tendinous tissue length increased
      with less stretched fascicle during the braking phase. In the subsequent push-off
      phase, the recoil of tendinous tissues became greater. These results suggest that
      the increased prestretch intensity has considerable influence on the process of
      storage and subsequent recoil of the elastic energy during the stretch-shortening
      cycle action.

PMID- 14594858
TI  - Aging and the skin blood flow response to the unloading of baroreceptors during
      heat and cold stress.
AB  - Control of skin blood flow (SkBF) is on the efferent arm of both thermoregulatory
      and nonthermoregulatory reflexes. To what extent aging may affect the SkBF
      response when these two reflex systems interact is unknown. To determine the
      response of aged skin to the unloading of baroreceptors in thermoneutral, cold
      stress, and heat stress conditions, sequential bouts of nonhypotensive lower body
      negative pressure (LBNP) were applied at -10, -20, and -30 mmHg in 14 young (18
      25 yr) and 14 older (63-78 yr) men. SkBF was measured by laser-Doppler
      velocimetry (averaged over 2 forearm sites), and data are expressed as percentage
      of maximal cutaneous vascular conductance (%CVC(max)). Total forearm blood flow
      was measured by venous occlusion plethysmography, and forearm vascular
      conductance (FVC) was calculated as the ratio of forearm blood flow to mean
      arterial pressure. In young men, all three intensities of LBNP in
      thermoneutrality decreased FVC significantly (P < 0.05), but FVC at -10 mmHg did
      not change in the older men. There were no significant LBNP effects on %CVC(max).
      Application of LBNP during cold stress did not significantly change %CVC(max) or
      FVC in either age group. During heat stress, -10 to -30 mmHg of LBNP decreased
      FVC significantly (P < 0.05) in both age groups, but these decreases were
      attenuated in the older men (P < 0.05). %CVC(max) decreased at -30 mmHg in the
      younger men only. These results suggest that older men have an attenuated skin
      vasoconstrictor response to the unloading of baroreceptors in heat stress
      conditions. Furthermore, the forearm vasoconstriction elicited by LBNP in older
      men reflects that of underlying tissue (i.e., muscle) rather than that of skin,
      whereas -30 mmHg LBNP also decreases SkBF in young hyperthermic men.

PMID- 14594859
TI  - Parabrachial neurons mediate dorsal periaqueductal gray evoked respiratory
      responses in the rat.
AB  - The neural substrates mediating autonomic components of the behavioral defense
      response reside in the periaqueductal gray (PAG). The cardiovascular components
      of the defense response evoked from the dorsal PAG (DPAG) have been well
      described and are dependent, in part, on the integrity of neurons in the region
      of the parabrachial nucleus as well as the rostral ventrolateral medulla.
      Descending pathways mediating the ventilatory response associated with activation
      of DPAG neurons are unknown. The present study was undertaken to test the
      hypothesis that parabrachial area neurons are also involved in mediating the
      respiratory response to DPAG stimulation. In urethane-anesthetized, spontaneously
      breathing rats, electrical stimulation of the DPAG significantly increased
      respiratory rate, arterial pressure, and heart rate. Changes in respiratory
      frequency were associated with significant decreases in inspiratory and
      expiratory durations. After bilateral inhibition of neurons in the lateral
      parabrachial nucleus (LPBN) region with 5 mM muscimol (n = 6), DPAG-evoked
      increases in respiration and heart rate were attenuated by 90 +/- 6 and 72 +/-
      13%, respectively. The pressor response evoked by DPAG stimulation, however, was
      attenuated by only 57 +/- 6%. Bilateral blockade of glutamate receptors with 20
      mM kynurenic acid (n = 6) in the LPBN also markedly attenuated DPAG-evoked
      increases in respiration and heart rate (65 +/- 15 and 53 +/- 9% reduction,
      respectively) but only modestly changed the DPAG-evoked pressor response (34 +/-
      16% reduction). These results demonstrate that LPBN neurons play a significant
      role in the DPAG-mediated respiratory component of behavioral defense responses.
      This finding supports previous work demonstrating that the dorsolateral pons
      plays a significant role in mediating most physiological adjustments associated
      with activation of the DPAG.

PMID- 14594860
TI  - Acute exposure to GH during exercise stimulates the turnover of free fatty acids
      in GH-deficient men.
AB  - The secretion of growth hormone (GH) increases acutely during exercise, but
      whether this is associated with the concomitant alterations in substrate
      metabolism has not previously been studied. We examined the effects of acute GH
      administration on palmitate, glucose, and protein metabolism before, during, and
      after 45 min of moderate-intensity aerobic exercise in eight GH-deficient men
      (mean age = 40.8 +/- 2.9 yr) on two occasions, with (+GH; 0.4 IU GH) and without
      GH administered (-GH). A group of healthy controls (n = 8, mean age = 40.4 +/-
      4.2 yr) were studied without GH. The GH replacement during exercise on the +GH
      study mimicked the endogenous GH profile seen in healthy controls. No significant
      difference in resting free fatty acid (FFA) flux was found between study days,
      but during exercise a greater FFA flux was found when GH was administered (211 +/
      26 vs. 168 +/- 28 micromol/min, P < 0.05) and remained elevated throughout
      recovery (P < 0.05). With GH administered, the exercise FFA flux was not
      significantly different from that observed in control subjects (188 +/- 14
      micromol/min), but the recovery flux was greater on the +GH day than in the
      controls (169 +/- 17 vs. 119 +/- 11 micromol/min, respectively, P < 0.01). A
      significant time effect (P < 0.01) for glucose rate of appearance from rest to
      exercise and recovery occurred in the GH-deficient adults and the controls,
      whereas there were no differences in glucose rate of disappearance. No
      significant effect across time was found for protein muscle balance. In
      conclusion, 1) acute exposure to GH during exercise stimulates the FFA release
      and turnover in GH-deficient adults, 2) GH does not significantly impact glucose
      or protein metabolism during exercise, and 3) the exercise-induced secretion of
      GH plays a significant role in the regulation of fatty acid metabolism.

PMID- 14594862
TI  - Venous occlusion to the lower limb attenuates vasoconstriction in the
      nonexercised limb during posthandgrip muscle ischemia.
AB  - We investigated the effects of increases in calf volume on cardiovascular
      responses during handgrip (HG) exercise and post-HG exercise muscle ischemia
      (PEMI). Seven subjects completed two trials: one control (no occlusion) and one
      venous occlusion (VO) session. Both trials included a baseline measurement
      followed by 15 min of rest (REST), 2 min of HG, and 2 min of PEMI. VO was applied
      at 100 mmHg via cuffs placed around both distal thighs during REST, HG, and PEMI.
      Mean arterial pressure, heart rate, forearm blood flow (FBF) in the nonexercised
      arm, and forearm vascular resistance (FVR) in the nonexercised arm (FVR) were
      measured. During REST and HG, there were no significant differences between
      trials in all parameters. During PEMI in the control trial, mean arterial
      pressure and FVR were significantly greater and FBF was significantly lower than
      baseline values (P < 0.05 for each). In contrast, in the VO trial, FBF and FVR
      responses were different from control responses. In the VO trial, FBF was
      significantly greater than in the control trial (4.7 +/- 0.5 vs. 2.5 +/- 0.3 ml x
      100 ml(-1) x min(-1), P < 0.05) and FVR was significantly lower (28.0 +/- 4.8 vs.
      49.1 +/- 4.6 units, respectively, P < 0.05). These results indicate that
      increases in vascular resistance in the nonexercised limb induced by activation
      of the muscle chemoreflex can be attenuated by increases in calf volume.

PMID- 14594861
TI  - Pathophysiological significance of peroxidative stress, neuronal damage, and
      membrane permeability in acute mountain sickness.
AB  - Free radical-mediated changes in vascular permeability and subsequent
      inflammatory response may be a contributory pathogenetic cofactor responsible for
      the development of neurological sequelae associated with acute mountain sickness
      (AMS). To investigate this, 49 subjects were examined at sea level and serially
      after rapid ascent to 4,559 m. Although the venous concentration of total
      creatine phosphokinase activity was measured in all subjects, a complementary
      examination of lipid peroxidation (F(2)-isoprostanes), inflammatory (TNF-alpha,
      IL-1beta, IL-2, IL-6, IL-8, C-reactive protein), and cerebrovascular tissue
      damage (neuron-specific enolase) biomarkers was confined to a subcohort of 24
      subjects. A selective increase (P < 0.05) in total creatine phosphokinase was
      observed in subjects diagnosed with AMS at high altitude (n = 25) compared with
      apparently healthy controls (n = 24). However, despite a marked increase in IL-6
      and C-reactive protein attributable primarily to subjects developing high
      altitude pulmonary edema, subcohort analyses demonstrated no selective
      differences in F(2)-isoprostanes, neuron-specific enolase, or remaining
      proinflammatory cytokines due to AMS (n = 14). The present findings are the first
      to demonstrate that free radical-mediated neuronal damage of sufficient degree to
      be detected in the peripheral circulation does not occur and is, therefore,
      unlikely to be an important, initiating event that is critical for the
      development of AMS. The pathophysiological significance of increased sarcolemmal
      membrane permeability and inflammatory response, either as a cause or
      epiphenomenon of AMS and/or high-altitude pulmonary edema, remains to be
      elucidated.

PMID- 14594863
TI  - Contribution of airway closure to chronic postbronchiolitis airway dysfunction in
      rats.
AB  - Genetically susceptible Brown Norway rats develop a chronic asthmalike syndrome
      after recovering from viral bronchiolitis at an early age. We hypothesized that
      airway closure is an important mechanism of airflow obstruction in
      postbronchiolitis rats. Rats were studied 8-12 wk after inoculation with Sendai
      virus or sterile vehicle at 3-4 wk of age. Under light pentobarbital anesthesia,
      rats were instrumented with an orotracheal catheter and an esophageal pressure
      monitor and placed in a total body plethysmograph. Lung volumes and forced
      expiratory maneuvers were measured using the Boyle's law method and software
      controlled valving of positive and negative pressures to elicit lung inflations
      and rapid deflations; pulmonary resistance was measured during spontaneous tidal
      breathing; and quasi-static pressure-volume curves were obtained with passive
      inflations and deflations in fully anesthetized, paralyzed rats. Compared with
      controls, the postbronchiolitis rats had elevated pulmonary resistance and
      reduced forced-expiratory volume in 0.2 s. Most of the reduced forced-expiratory
      volume in 0.2 s was associated with reduced forced vital capacity, indicating
      premature airway closure as a prominent mechanism. The reduced airflow in
      postbronchiolitis rats was highly dependent on lung volume, being nearly normal
      at 70% lung capacity, but sevenfold less than normal at 30% lung capacity.
      Increased respiratory system hysteresis between functional reserve capacity and
      total lung capacity was evidence for increased airway closure at normal end
      expiratory lung volumes in postbronchiolitis rats. We conclude that airway
      instability and closure is a prominent mechanism of the chronic airway
      dysfunction in rats that have recovered from viral bronchiolitis at an early age.

PMID- 14594865
TI  - Mechanical state of airway smooth muscle at very short lengths.
AB  - Although the shortening of smooth muscle at physiological lengths is dominated by
      an interaction between external forces (loads) and internal forces, at very short
      lengths, internal forces appear to dominate the mechanical behavior of the active
      tissue. We tested the hypothesis that, under conditions of extreme shortening and
      low external force, the mechanical behavior of isolated canine tracheal smooth
      muscle tissue can be understood as a structure in which the force borne and
      exerted by the cross bridge and myofilament array is opposed by radially disposed
      connective tissue in the presence of an incompressible fluid matrix (cellular and
      extracellular). Strips of electrically stimulated tracheal muscle were allowed to
      shorten maximally under very low afterload, and large longitudinal sinusoidal
      vibrations (34 Hz, 1 s in duration, and up to 50% of the muscle length before
      vibration) were applied to highly shortened (active) tissue strips to produce
      reversible cross-bridge detachment. During the vibration, peak muscle force fell
      exponentially with successive forced elongations. After the episode, the muscle
      either extended itself or exerted a force against the tension transducer,
      depending on external conditions. The magnitude of this effect was proportional
      to the prior muscle stiffness and the amplitude of the vibration, indicating a
      recoil of strained connective tissue elements no longer opposed by cross-bridge
      forces. This behavior suggests that mechanical behavior at short lengths is
      dominated by tissue forces within a tensegrity-like structure made up of
      connective tissue, other extracellular matrix components, and active contractile
      elements.

PMID- 14594864
TI  - Electrical stimulation of human lower extremities enhances energy consumption,
      carbohydrate oxidation, and whole body glucose uptake.
AB  - Our laboratory has recently demonstrated that low-frequency electrical
      stimulation (ES) of quadriceps muscles alone significantly enhanced glucose
      disposal rate (GDR) during euglycemic clamp (Hamada T, Sasaki H, Hayashi T,
      Moritani T, and Nakao K. J Appl Physiol 94: 2107-2112, 2003). The present study
      is further follow-up to examine the acute metabolic effects of ES to lower
      extremities compared with voluntary cycle exercise (VE) at identical intensity.
      In eight male subjects lying in the supine position, both lower leg (tibialis
      anterior and triceps surae) and thigh (quadriceps and hamstrings) muscles were
      sequentially stimulated to cocontract in an isometric manner at 20 Hz with a 1-s
      on-off duty cycle for 20 min. Despite small elevation of oxygen uptake by 7.3 +/-
      0.3 ml x kg(-1) x min(-1) during ES, the blood lactate concentration was
      significantly increased by 3.2 +/- 0.3 mmol/l in initial period (5 min) after the
      onset of the ES (P < 0.01), whereas VE showed no such changes at identical oxygen
      uptake (7.5 +/- 0.3 ml x kg(-1) x min(-1)). ES also induced enhanced whole body
      carbohydrate oxidation as shown by the significantly higher respiratory gas
      exchange ratio than with VE (P < 0.01). These data indicated increased anaerobic
      glycolysis by ES. Furthermore, whole body glucose uptake determined by GDR during
      euglycemic clamp demonstrated a significant increase during and after the
      cessation of ES for at least 90 min (P < 0.01). This post-ES effect was
      significantly greater than that of the post-VE period (P < 0.01). These results
      suggest that ES can substantially enhance energy consumption, carbohydrate
      oxidation, and whole body glucose uptake at low intensity of exercise.
      Percutaneous ES may become a therapeutic utility to enhance glucose metabolism in
      humans.

PMID- 14594866
TI  - Effect of carbohydrate intake on net muscle protein synthesis during recovery
      from resistance exercise.
AB  - The purpose of this study was to determine the effect of ingestion of 100 g of
      carbohydrates on net muscle protein balance (protein synthesis minus protein
      breakdown) after resistance exercise. Two groups of eight subjects performed a
      resistance exercise bout (10 sets of 8 repetitions of leg presses at 80% of 1
      repetition maximum) before they rested in bed for 4 h. One group (CHO) received a
      drink consisting of 100 g of carbohydrates 1 h postexercise. The other group
      (Pla) received a noncaloric placebo drink. Leg amino acid metabolism was
      determined by infusion of 2H5- or 13C6-labeled phenylalanine, sampling from
      femoral artery and vein, and muscle biopsies from vastus lateralis. Drink intake
      did not affect arterial insulin concentration in Pla, whereas insulin increased
      several times after the drink in CHO (P < 0.05 vs. Pla). Arterial phenylalanine
      concentration fell slightly after the drink in CHO. Net muscle protein balance
      between synthesis and breakdown did not change in Pla, whereas it improved in CHO
      from -17 +/- 3 nmol.ml(-1).100 ml leg(-1) before drink to an average of -4 +/- 4
      and 0 +/- 3 nmol.ml(-1).100 ml leg(-1) during the second and third hour after the
      drink, respectively (P < 0.05 vs. Pla during last hour). The improved net balance
      in CHO was due primarily to a progressive decrease in muscle protein breakdown.
      We conclude that ingestion of carbohydrates improved net leg protein balance
      after resistance exercise. However, the effect was minor and delayed compared
      with the previously reported effect of ingestion of amino acids.

PMID- 14594867
TI  - A novel method for measuring dynamic changes in cell volume.
AB  - Many cell types regulate their volume in response to extracellular tonicity
      changes through a complex series of adaptive mechanisms. Several methods that are
      presently used to measure cell volume changes include Coulter counters,
      fluorescent techniques, electronic impedance, and video microscopy. Although
      these methods are widely used and accepted, there are limitations associated with
      each technique. This paper describes a new method to measure changes in cell
      volume based on the principle that fluid flow within a rigid system is well
      determined. For this study, cos-7 cells were plated to line the inner lumen of a
      glass capillary and stimulated to swell or shrink by altering the osmolarity of
      the perfusing solution. The cell capillary was connected in series with a blank
      reference capillary, and differential pressure changes across each tube were
      monitored. The advantages of this method include 1) ability to continuously
      monitor changes in volume during rapid solution changes, 2) independence from
      cell morphology, 3) presence of physiological conditions with cell surface
      contacts and cell-cell interactions, 4) no phototoxic effects such as those
      associated with fluorescent methods, and 5) ability to report from large
      populations of cells. With this method, we could detect the previously
      demonstrated enhanced volume regulation of cells overexpressing the membrane
      phosphoprotein phospholemman, which has been implicated in osmolyte transport.

PMID- 14594869
TI  - Techniques for comprehensive two dimensional echocardiographic assessment of left
      ventricular systolic function.

PMID- 14594871
TI  - A clinical approach to the assessment of left ventricular diastolic function by
      Doppler echocardiography: update 2003.

PMID- 14594872
TI  - Screening for left ventricular dysfunction in the community: role of hand held
      echocardiography and brain natriuretic peptides.

PMID- 14594870
TI  - Tissue Doppler, strain, and strain rate echocardiography for the assessment of
      left and right systolic ventricular function.
AB  - Tissue Doppler (TDE), strain, and strain rate echocardiography are emerging real
      time ultrasound techniques that provide a measure of wall motion. They offer an
      objective means to quantify global and regional left and right ventricular
      function and to improve the accuracy and reproducibility of conventional
      echocardiography studies. Radial and longitudinal ventricular function can be
      assessed by the analysis of myocardial wall velocity and displacement indices, or
      by the analysis of wall deformation using the rate of deformation of a myocardial
      segment (strain rate) and its deformation over time (strain). A quick and easy
      assessment of left ventricular ejection fraction is obtained by mitral annular
      velocity measurement during a routine study, especially in patients with poor
      endocardial definition or abnormal septal motion. Strain rate and strain are less
      affected by passive myocardial motion and tend to be uniform throughout the left
      ventricle in normal subjects. This paper reviews the underlying principles of
      TDE, strain, and strain rate echocardiography and discusses currently available
      quantification tools and clinical applications.

PMID- 14594873
TI  - Left ventricular assessment using real time three dimensional echocardiography.

PMID- 14594874
TI  - Diastolic heart failure: fact or fiction?

PMID- 14594875
TI  - Large B cell lymphoma with cardiac infiltration.

PMID- 14594876
TI  - Judicious use of transthoracic echocardiography in the diagnosis of infective
      endocarditis.

PMID- 14594878
TI  - Are troponins confusing?

PMID- 14594880
TI  - Unusual morphologic changes in apical hypertrophic cardiomyopathy.

PMID- 14594879
TI  - C reactive protein for risk stratification in acute coronary syndromes? Verdict:
      unproven.
AB  - Although C reactive protein is intimately involved with the pathogenic mechanisms
      that drive acute coronary syndromes, there is no evidence that it is helpful for
      identifying patient groups who might benefit from particular treatment strategies

PMID- 14594881
TI  - Role of myocardial perfusion imaging for risk stratification in suspected or
      known coronary artery disease.
AB  - Nuclear cardiology is an evolving specialty that has recently benefited from
      technological and radiopharmaceutical advances. As a result there has been an
      increase in the accuracy of myocardial perfusion imaging (MPI) with gated single
      photon emission computed tomography (SPECT) for assessing the diagnosis and
      prognosis of coronary artery disease. Moreover, ECG gated SPECT allows the
      simultaneous assessment of both myocardial perfusion and left ventricular
      function, which provides additional prognostic value. With increasing concern
      over early detection of coronary artery disease and its effective treatment,
      myocardial perfusion imaging is ideally placed to provide a full "one stop"
      functional assessment for any patient, irrespective of their exercise capacity.
      This applies not only to patients with chest pain but also to those with
      myocardial infarction, revascularisation, and heart failure, and those being
      assessed for non-cardiac surgery. The focus of this review is the use of
      myocardial perfusion imaging in risk stratification for coronary artery disease.

PMID- 14594882
TI  - Improved detection of protruding apical thrombus with contrast echocardiography.

PMID- 14594883
TI  - Survival differences between heart failure in general practices and in hospitals.
AB  - OBJECTIVES: To compare the survival of patients thought to have heart failure in
      general practice (GP-HF) with that of patients with heart failure in hospital
      (hospital-HF), patients with heart disease but without heart failure (non-HF),
      and a control group without heart disease. DESIGN AND SETTING: Cross sectional
      study from general practice with a prospective follow up from 5.3 to 7.4 years.
      PARTICIPANTS: 2157 community participants, 1999 of whom lived outside nursing
      homes, were selected because they were registered with four general practitioners
      at entry. Study participants were divided into the four groups after a review of
      general practice case notes, questionnaires, and interviews. MAIN OUTCOME
      MEASURES: Five year survival and multivariate predictors of all cause mortality.
      RESULTS: Five year survival was 76% in the control group (n = 571, mean age at
      entry 74.1 years), 71% in non-HF patients (n = 218, 74.4 years), 61% in GP-HF
      patients (n = 67, 75.8 years), and 39% in hospital-HF patients (n = 33, 76.7
      years). The median survival times were 6.8 years for GP-HF patients and 3.9 years
      for hospital-HF patients. Significant predictors of mortality in the multivariate
      Cox model of 1979 patients living outside nursing homes were hospital-HF (hazard
      ratio (HR) 2.1, p = 0.002), GP-HF (HR 1.7, p = 0.004), non-HF heart disease (HR
      1.4, p = 0.03), previous myocardial infarction (HR 1.6, p = 0.04), no response to
      questionnaire (HR 2.0, p < 0.0001), higher age (for every 10 years, HR 2.4, p <
      0.0001), and male sex (HR 2.1, p < 0.0001). Other factors such as atrial
      fibrillation, hypertension, and diabetes were not significant. CONCLUSION: Heart
      failure in general practice is associated with a worse survival than that seen in
      the control group but is better than for patients who have been treated at least
      once for heart failure in a hospital.

PMID- 14594885
TI  - ICD lead implantation via persistent left superior vena cava.

PMID- 14594884
TI  - Circulating concentrations of cardiac proteins indicate the severity of
      congestive heart failure.
AB  - OBJECTIVE: To test the hypothesis that myocardium specific proteins may be useful
      markers for evaluating the severity of congestive heart failure. METHODS: Serum
      concentrations of myosin light chain I (MLC-I), heart fatty acid binding protein
      (H-FABP), creatine kinase isoenzyme MB (CK-MB), and troponin T (TnT) and plasma
      concentrations of brain natriuretic peptide (BNP) were determined in 48 patients
      with acute deterioration of congestive heart failure, both before and after
      effective treatment. RESULTS: Before treatment, MLC-I (mean (SEM) 3.2 (2.2)
      microg/l), H-FABP (9.0 (3.5) microg/l), TnT (30 (21) ng/l), and BNP (761 (303)
      ng/l) were higher than the normal reference range, and concentrations of CK-MB
      (5.4 (2.9) microg/l) were near normal. Treatment of congestive heart failure with
      conventional medication significantly decreased the concentrations of MLC-I (1.2
      (0.3) microg/l, p < 0.0001), H-FABP (6.0 (2.0) microg/l, p < 0.0001), CK-MB (2.9
      (1.5) microg/l, p < 0.0001), TnT (9 (1) ng/l, p < 0.001), and BNP (156 (118)
      ng/l, p < 0.0001). The decreases in H-FABP and CK-MB concentrations after
      treatment correlated with the decrease in BNP concentrations (p < 0.05). The
      absolute concentrations of MLC-I, H-FABP, CK-MB, and TnT correlated positively
      with those of BNP (p < 0.01). CONCLUSIONS: These findings suggest that MLC-I, H
      FABP, CK-MB, and TnT may be used as reliable markers for the evaluation of the
      severity of congestive heart failure.

PMID- 14594886
TI  - Effects of digoxin on left atrial function in heart failure.
AB  - OBJECTIVE: To investigate the effects of digoxin on left atrial (LA) function in
      patients with congestive heart failure and dilated left atria. PATIENTS: 30
      patients with enlarged left atrium (maximum LA diameter > 4 mm) caused by heart
      failure (New York Heart Association functional class III or IV) were studied
      before and after treatment with digoxin (0.25 mg orally for 12 days). Digoxin was
      also administered to 30 normal participants who served as controls. MAIN OUTCOME
      MEASURES: LA active (AEF) and passive emptying fractions (PEF), reservoir
      fraction (RF), kinetic energy (KE), and mean velocity of circumferential atrial
      fibre shortening (Vcf) were calculated from echocardiographic measurements of LA
      volumes and transmitral Doppler flow velocities at baseline and on the third,
      sixth, eighth, and 12th day after digoxin administration. RESULTS: LA AEF, PEF,
      RF, KE, and Vcf were significantly lower in patients than in controls (p <
      0.001). LA AEF, PEF, RF, KE, and Vcf increased significantly both in patients and
      controls after digoxin administration (p < 0.001). This increase was greater in
      patients than in controls (p < 0.001). KE was linearly correlated with LA volume
      at the onset of atrial systole in all participants. The slope and the intercept
      of this relation were significantly increased after digoxin both in patients and
      in controls (p < 0.001). CONCLUSIONS: LA performance is impaired in patients with
      heart failure. Dilated atria manifest atrial failure. Digoxin improves LA
      performance and LA contractility both in dilated and in normal atria. The effects
      of digoxin on LA contractility are augmented in the failing atria compared with
      the normal atria.

PMID- 14594887
TI  - Coronary rupture as a rare cause of acute myocardial ischaemia two months after
      angioplasty and stenting.

PMID- 14594889
TI  - Echocardiographic detection of systemic air embolism during positive pressure
      ventilation.

PMID- 14594888
TI  - Prevalence and clinical significance of incidental paraprosthetic valvar
      regurgitation: a prospective study using transoesophageal echocardiography.
AB  - OBJECTIVE: To assess the prevalence, mechanisms, and significance of
      paraprosthetic regurgitation detected incidentally by transoesophageal
      echocardiography (TOE) in patients after heart valve replacement. DESIGN:
      Prospective observational study. SETTING: Tertiary referral centre. PATIENTS: 360
      consecutive patients (mean (SD) age 65.8(9.5) years, 193 women) undergoing
      elective first ever valve replacement. METHODS: Postoperative and follow up TOE,
      and tests for haemolysis and anaemia. RESULTS: There were 243 aortic, 90 mitral,
      and 27 double valve replacements, using 316 mechanical and 44 tissue valves,
      giving 270 aortic and 117 mitral valves. One patient with severe paraprosthetic
      mitral regurgitation underwent immediate reoperation and was excluded from
      subsequent analyses. Paraprosthetic jets were detected around 16 (6%) of the
      aortic and 38 (32%) of the mitral valves (p < 0.05) at the postoperative study.
      Follow up TOE was available for 151 aortic and 67 mitral valves, 0.9 (0.5) years
      after operation. Paraprosthetic jets were present in 15 (10%) of the aortic and
      10 (15%) of the mitral valves (NS). Two thirds of the aortic and a fifth of the
      mitral jets were new. Paraprosthetic jets were more common in aortic valves in a
      supra-annular (12 of 88, 14%) than in an intra-annular position (4 or 182, 2%; p
      < 0.005) and in mitral valves inserted with continuous (36 of 88, 41%) rather
      than interrupted sutures (2 of 28, 7%; p < 0.001). Lactate dehydrogenase
      concentration was higher in patients with paraprosthetic jets than in those
      without (752 (236) v 654 (208) IU/l, p < 0.001). Haemoglobin and haptoglobin
      concentrations were not different. CONCLUSIONS: Small paraprosthetic leaks are
      common, are related to surgical factors, are not associated with increased
      subclinical haemolysis, and are benign during the first year after heart valve
      replacement.

PMID- 14594890
TI  - Quantification of regional left ventricular function in Q wave and non-Q wave
      dysfunctional regions by tissue Doppler imaging in patients with ischaemic
      cardiomyopathy.
AB  - OBJECTIVE: To quantify regional left ventricular (LV) function and contractile
      reserve in Q wave and non-Q wave regions in patients with previous myocardial
      infarction. DESIGN: An observational study. SETTING: Tertiary care centre.
      PATIENTS: 81 patients with previous myocardial infarction and depressed LV
      function. INTERVENTIONS: All patients underwent surface ECG at rest and pulsed
      wave tissue Doppler imaging at rest and during low dose dobutamine infusion. The
      left ventricle was divided into four major regions (anterior, inferoposterior,
      septal, and lateral). Severely hypokinetic, akinetic, and dyskinetic regions on
      two dimensional echocardiography at rest were considered dysfunctional. MAIN
      OUTCOME MEASURES: Regional myocardial systolic velocity (Vs) at rest and the
      change in Vs during low dose dobutamine infusion (DeltaVs) in dysfunctional
      regions with and without Q waves on surface ECG. RESULTS: 220 (69%) regions were
      dysfunctional; 60 of these regions corresponded to Q waves and 160 were not
      related to Q waves. Vs and DeltaVs were lower in dysfunctional than in non
      dysfunctional regions (mean (SD) Vs 6.2 (1.9) cm/s v 7.1 (1.7) cm/s (p < 0.001),
      and DeltaVs 1.9 (1.9) cm/s v 2.6 (2.5) cm/s (p = 0.009), respectively). There
      were no significant differences in Vs and DeltaVs among dysfunctional regions
      with and without Q waves (Q wave regions: Vs 6.2 (1.8) cm/s, DeltaVs 1.6 (2.2)
      cm/s; non-Q wave regions: Vs 6.3 (1.9) cm/s, DeltaVs 2.0 (2.0) cm/s).
      CONCLUSIONS: Quantitative pulsed wave tissue Doppler demonstrated that, among
      dysfunctional regions, Q waves on the ECG do not indicate more severe
      dysfunction, and myocardial contractile reserve is comparable in Q wave and non-Q
      wave dysfunctional myocardium.

PMID- 14594891
TI  - Spontaneous coronary artery dissection in a pre-menopausal woman presenting with
      transient ST segment elevation.

PMID- 14594893
TI  - Artefactual occlusion of the left subclavian artery during graft angiography.

PMID- 14594894
TI  - Right atrial tumour mass of unusual origin.

PMID- 14594892
TI  - A meta-analysis comparing the prognostic accuracy of six diagnostic tests for
      predicting perioperative cardiac risk in patients undergoing major vascular
      surgery.
AB  - OBJECTIVE: To evaluate the discriminatory value and compare the predictive
      performance of six non-invasive tests used for perioperative cardiac risk
      stratification in patients undergoing major vascular surgery. DESIGN: Meta
      analysis of published reports. METHODS: Eight studies on ambulatory
      electrocardiography, seven on exercise electrocardiography, eight on radionuclide
      ventriculography, 23 on myocardial perfusion scintigraphy, eight on dobutamine
      stress echocardiography, and four on dipyridamole stress echocardiography were
      selected, using a systematic review of published reports on preoperative non
      invasive tests from the Medline database (January 1975 and April 2001). Random
      effects models were used to calculate weighted sensitivity and specificity from
      the published results. Summary receiver operating characteristic (SROC) curve
      analysis was used to evaluate and compare the prognostic accuracy of each test.
      The relative diagnostic odds ratio was used to study the differences in
      diagnostic performance of the tests. RESULTS: In all, 8119 patients participated
      in the studies selected. Dobutamine stress echocardiography had the highest
      weighted sensitivity of 85% (95% confidence interval (CI) 74% to 97%) and a
      reasonable specificity of 70% (95% CI 62% to 79%) for predicting perioperative
      cardiac death and non-fatal myocardial infarction. On SROC analysis, there was a
      trend for dobutamine stress echocardiography to perform better than the other
      tests, but this only reached significance against myocardial perfusion
      scintigraphy (relative diagnostic odds ratio 5.5, 95% CI 2.0 to 14.9).
      CONCLUSIONS: On meta-analysis of six non-invasive tests, dobutamine stress
      echocardiography showed a positive trend towards better diagnostic performance
      than the other tests, but this was only significant in the comparison with
      myocardial perfusion scintigraphy. However, dobutamine stress echocardiography
      may be the favoured test in situations where there is valvar or left ventricular
      dysfunction.

PMID- 14594895
TI  - Long term follow up after elective percutaneous coronary intervention for
      unprotected non-bifurcational left main stenosis: is it time to change the
      guidelines?
AB  - BACKGROUND: According to the American College of Cardiology/American Heart
      Association guidelines, percutaneous coronary intervention (PCI) for left main
      coronary artery (LMCA) stenosis is contraindicated and coronary artery bypass
      graft surgery (CABG) is preferred. However, PCI of the LMCA is performed under
      exceptional circumstances. OBJECTIVE: To analyse the data of patients who
      underwent PCI of the unprotected LMCA in St Antonius Hospital, Nieuwegein,
      Netherlands. RESULTS: In a database of 17 683 PCI procedures, 71 patients (0.4%)
      were found with non-bifurcational LMCA stenosis who underwent an elective PCI
      between 1991 and 2001. Ages ranged from 26.7-86.5 years. Severe concomitant
      disease was the most frequent argument in favour of PCI instead of CABG. PCI
      consisted of only balloon angioplasty in 23 cases (32.4%). A stent was used in 46
      cases (64.4%). Average follow up was 43 months (range 0-121 months). One patient
      died one day after the procedure. The total one year survival rate was 98.6%
      (70/71). Seven patients died during the follow up period, mostly because of non
      cardiac reasons. The annual mortality rate was 2.5%. Recurrent elective
      percutaneous transluminal coronary angioplasty for restenosis of the LMCA was
      performed in one patient (1.4%) six weeks after the initial procedure. CABG was
      required in 13 patients (18.3%) throughout the follow up period. CONCLUSION:
      These results suggest that at highly experienced centres, elective PCI of the non
      bifurcational LMCA can be performed safely where the anatomy is suitable.

PMID- 14594896
TI  - Long term somatic growth after repair of tetralogy of Fallot: evidence for
      restoration of genetic growth potential.
AB  - OBJECTIVE: To compare actual with predicted long term growth after early repair
      of tetralogy of Fallot (TOF). DESIGN: Serial preoperative and postoperative
      anthropometric data were converted with z scores. The presence of restrictive
      physiology was assessed by echocardiography. PATIENTS: 45 otherwise healthy
      patients who underwent repair at median age 1.6 years (range 0.2-4.9) were
      studied. Predicted height was determined from mid-parental height corrected for
      sex. RESULTS: Mean (SD) weight and height z scores at the time of surgery were
      significantly depressed (-1.04 (0.82) and -0.93 (0.95), respectively; p < 0.0001
      for both). At latest follow up at a median age of 14.2 years (range 11-20.5),
      mean weight and height z scores were 0.16 (1.1) and -0.05 (0.81) (p = 0.32 and p
      = 0.41, respectively). The improvement between surgical and late weight and
      height z scores was significant (p < 0.0001 for each comparison). Catch up growth
      was largely complete within two years. Age at correction, duration of follow up,
      and prior surgical procedures were unrelated to growth. Mean current height z
      scores were similar to those predicted by mid-parental height. Patients with
      restrictive right ventricular physiology (n = 24) had a significantly greater
      late z score for weight (0.49 v -0.34; p = 0.01), with a similar trend for
      height. Low birth weight patients experienced comparable catch up growth but
      remained shorter than patients with normal birth weight (mean height z score 
      0.64 v 0.06; p = 0.03). CONCLUSIONS: Early repair of TOF results in significant
      acceleration of weight and height, with normalisation of long term growth and
      fulfilment of genetic growth potential.

PMID- 14594898
TI  - Atrial septostomy for pulmonary arterial hypertension.

PMID- 14594900
TI  - Symptomatic occlusion of the access vein after pacemaker or ICD lead extraction.

PMID- 14594902
TI  - Use of 3 French catheters for diagnostic and interventional procedures in
      newborns and small infants.

PMID- 14594903
TI  - The human coronary collateral circulation.

PMID- 14594904
TI  - Thrombolysis: newer thrombolytic agents and their role in clinical medicine.

PMID- 14594908
TI  - How much of the burden of schizophrenia is alleviated by treatment?

PMID- 14594906
TI  - Drug induced QT prolongation and torsades de pointes.

PMID- 14594909
TI  - Progress in research on dual disorders.

PMID- 14594910
TI  - Prospects for Chapter V of ICD-11 and DSM-V.

PMID- 14594911
TI  - Suicide and mental disorders: do we know enough?

PMID- 14594912
TI  - Predictors of efficacy in depression prevention programmes. Meta-analysis.
AB  - BACKGROUND: Worldwide, 340 million people are affected by depression, with high
      comorbid, social and economic costs. AIMS: To identify potential predictors of
      effect in prevention programmes. METHOD: A meta-analysis was made of 69
      programmes to reduce depression or depressive symptoms. RESULTS: The weighted
      mean effect size of 0.22 was effective for different age groups and different
      levels of risk, and in reducing risk factors and depressive or psychiatric
      symptoms. Programmes with larger effect sizes were multi-component, included
      competence techniques, had more than eight sessions, had sessions 60-90 min long,
      had a high quality of research design and were delivered by a health care
      provider in targeted programmes. Older people benefited from social support,
      whereas behavioural methods were detrimental. CONCLUSIONS: An 11% improvement in
      depressive symptoms can be achieved through prevention programmes. Single trial
      evaluations should ensure high quality of the research design and detailed
      reporting of results and potential predictors.

PMID- 14594913
TI  - Describing, explaining or predicting mental health care costs: a guide to
      regression models. Methodological review.
AB  - BACKGROUND: Analysis of the patterns of variation in health care costs and the
      determinants of these costs (including treatment differences) is an increasingly
      important aspect of research into the performance of mental health services.
      AIMS: To encourage both investigators of the variation in health care costs and
      the consumers of their investigations to think more critically about the precise
      aims of these investigations and the choice of statistical methods appropriate to
      achieve them. METHOD: We briefly describe examples of regression models that
      might be of use in the prediction of mental health costs and how one might choose
      which one to use for a particular research project. CONCLUSIONS: If the
      investigators are primarily interested in explanatory mechanisms then they should
      seriously consider generalised linear models (but with careful attention being
      paid to the appropriate error distribution). Further insight is likely to be
      gained through the use of two-part models. For prediction we recommend regression
      on raw costs using ordinary least-square methods. Whatever method is used,
      investigators should consider how robust their methods might be to incorrect
      distributional assumptions (particularly in small samples) and they should not
      automatically assume that methods such as bootstrapping will allow them to ignore
      these problems.

PMID- 14594914
TI  - Paternal age and risk for schizophrenia.
AB  - BACKGROUND: Previously reported associations between advancing paternal age and
      schizophrenia could be due to an increase in paternal germ cell mutations or be
      confounded by heritable personality traits associated with schizophrenia that
      result in delayed parenthood. AIMS: To investigate this association while
      adjusting for personality traits related to poor social integration in the
      subjects. METHOD: A cohort of 50,087 adolescent males was followed up by record
      linkage to determine hospital admissions for schizophrenia between 1970 and 1996.
      RESULTS: Advancing paternal age was associated with an increased risk of
      developing schizophrenia in a 'dose-dependent' manner. The adjusted odds ratio
      for each 10-year increase in paternal age was 1.3 (95% CI 1.0-1.5; P=0.015).
      CONCLUSIONS: Advancing paternal age is an independent risk factor for
      schizophrenia. Adjusting for social integration in subjects made little
      difference to this association, consistent with the hypothesis that advancing
      paternal age may increase liability to schizophrenia owing to accumulating germ
      cell mutations.

PMID- 14594915
TI  - Chromosome 22q11 deletions, velo-cardio-facial syndrome and early-onset
      psychosis. Molecular genetic study.
AB  - BACKGROUND: Velo-cardio-facial syndrome (VCFS) is associated with interstitial
      deletions of chromosome 22q11. About 30% of patients with VCFS have psychosis,
      and the rate of these deletions in schizophrenia has been reported to be about
      1%. Even higher rates of VCFS deletions have been reported for childhood-onset
      schizophrenia. AIMS: To test the hypothesis that there is an increased rate of
      VCFS among patients with early-onset psychosis (age at onset <18 years). We
      screened 192 early-onset patients and 329 patients with adult-onset
      schizophrenia. METHOD: We genotyped the patients and 444 healthy controls for
      hemizygosity of five microsatellite markers and one single nucleotide
      polymorphism that map to the 22q11-deleted region. RESULTS: One patient had a
      VCFS deletion, confirmed with semi-quantitative polymerase chain reaction. None
      of the controls showed a pattern of genotypes consistent with hemizygosity.
      CONCLUSIONS: VCFS may be less frequent among patients with psychosis than
      previously suggested; this rate is not increased among early-onset patients.

PMID- 14594916
TI  - Size of hippocampal pyramidal neurons in schizophrenia.
AB  - BACKGROUND: Meta-analyses of hippocampal size have indicated that this structure
      is smaller in schizophrenia. This could reflect a reduction in the size of
      constituent neurons or a reduced number of neurons. AIMS: To measure the size of
      hippocampal pyramidal neurons in the brains of people with and without
      schizophrenia. METHOD: Pyramidal neuron size in hippocampal subfields was
      estimated stereologically from sections taken at 5 mm intervals throughout the
      whole length of right and left hippocampi from the brains of 13 people with
      schizophrenia and 16 controls. Results were assessed using repeated-measures
      analysis of covariance looking for a main effect of diagnosis and gender, and
      interactions of these with side. RESULTS: We were unable to detect significant
      differences related to diagnosis, gender or side for any hippocampal subfield for
      this series of cases. CONCLUSIONS: For this series of brains, hippocampal cell
      size is unchanged in schizophrenia.

PMID- 14594917
TI  - Cognitive-behavioural therapy and motivational intervention for schizophrenia and
      substance misuse. 18-month outcomes of a randomised controlled trial.
AB  - BACKGROUND: Comorbid substance misuse in people with schizophrenia is associated
      with poor clinical and social outcomes. There are few studies of psychological
      treatments for this population and little long-term follow-up of their benefits.
      AIMS: To investigate symptom, substance use, functioning and health economy
      outcomes for patients with schizophrenia and their carers 18 months after a
      cognitive-behavioural treatment (CBT) programme. METHOD: Patients with dual
      diagnosis from a randomised controlled trial of motivational intervention,
      individual CBT and family intervention were assessed on multiple outcomes at 18
      month follow-up. Carers were assessed on symptom, functioning and needs over 12
      months. Health economy data were collected over 18 months. RESULTS: There were
      significant improvements in patient functioning compared with routine care over
      18 months. No significant differences between treatment groups were found in
      carer or cost outcomes. CONCLUSIONS: The treatment programme was superior to
      routine care on outcomes relating to illness and service use, and the cost was
      comparable to the control treatment.

PMID- 14594918
TI  - Cost-effectiveness of current and optimal treatment for schizophrenia.
AB  - BACKGROUND: This paper is part of a project to identify the proportion of the
      burden of each mental disorder averted by current and optimal interventions, and
      the cost-effectiveness of both. AIMS: To use epidemiological data on
      schizophrenia to model the cost-effectiveness of current and optimal treatment.
      METHOD: Calculate the burden of schizophrenia in the years lived with disability
      (YLD) component of disability-adjusted life-years lost, the proportion averted by
      current interventions, the proportion that could be averted by optimal treatment
      and the cost-effectiveness of both. RESULTS: Current interventions avert some 13%
      of the burden, whereas 22% could be averted by optimal treatment. Current
      interventions cost about AUS 200,000 dollars per YLD averted, whereas optimal
      treatment at a similar cost could increase the number of YLDs averted by two
      thirds. Even so, the majority of the burden of schizophrenia remains unavertable.
      CONCLUSIONS: Optimal treatment is affordable within the present budget and should
      be implemented.

PMID- 14594920
TI  - Assessing the value of assertive outreach. Qualitative study of process and
      outcome generation in the UK700 trial.
AB  - BACKGROUND: It is unclear why intensive case management (ICM) failed to reduce
      hospitalisation in the UK700 trial. AIMS: To investigate outcome generation in
      the UK700 trial. METHOD: A qualitative investigation was undertaken in one UK700
      centre. RESULTS: Both intensive and standard case management practised individual
      casework, employed assertive outreach with comparable frequency, and performed
      similarly in the out-patient management of emergencies and in-patient discharge.
      However, ICM was advantaged in managing some non-compliance and undertaking
      casework that prevented psychiatric emergencies. Absence of team-based management
      and bureaucratised access to social care limited the impact of these differences
      on outcomes and the effective practice of assertive outreach, although this was
      relevant to only a sub-population of patients. CONCLUSIONS: The impact of ICM was
      undermined by organisational factors. Sensitive anticipatory casework, which
      prevents psychiatric emergencies, may make ICM more effective than an exclusive
      focus on assertive outreach. Our findings demonstrate the value of qualitative
      research in evaluating complex interventions.

PMID- 14594921
TI  - Choking deaths: the role of antipsychotic medication.
AB  - BACKGROUND: An increased risk of choking associated with antipsychotic medication
      has been repeatedly postulated. AIMS: To examine this association in a large
      number of cases of choking deaths. METHOD: Cases of individuals who had died
      because of choking were linked with a case register recording contacts with
      public mental health services. The actual and expected rates of psychiatric
      disorder and the presence of psychotropic medication in post-mortem blood samples
      were compared. RESULTS: The 70 people who had choked to death were over 20 times
      more likely to have been treated previously for schizophrenia. They were also
      more likely to have had a prior organic psychiatric syndrome. The risk for those
      receiving thioridazine or lithium was, respectively, 92 times and 30 times
      greater than expected. Other antipsychotic and psychotropic drugs were not over
      represented. CONCLUSIONS: The increased risk of death in people with
      schizophrenia may be a combination of inherent predispositions and the use of
      specific antipsychotic drugs. The increased risk of choking in those with organic
      psychiatric syndromes is consistent with the consequences of compromised
      neurological competence.

PMID- 14594923
TI  - Capacity building through multi-disciplinary research: a report from Sri Lanka.

PMID- 14594922
TI  - Psychological disturbance associated with sexual abuse in people with learning
      disabilities. Case-control study.
AB  - BACKGROUND: The association between sexual abuse, mental health and behavioural
      problems in people with learning disabilities has not previously been examined in
      a controlled study. AIMS: To identify symptoms of psychological disturbance in
      adults with and without a confirmed history of sexual abuse. METHOD: The study
      used a matched (1:1) case-control design comparing 54 adults who had experienced
      sexual abuse with 54 adults with no reported history of abuse. The two groups
      were selected from a community population of adults with learning disabilities
      living in residential care, and compared for selected psychiatric diagnoses and
      for scores on measures of disturbed behaviour. RESULTS: Sexual abuse was
      associated with increased rates of mental illness and behavioural problems, and
      with symptoms of post-traumatic stress. Psychological reactions to abuse were
      similar to those observed in the general population, but with the addition of
      stereotypical behaviour. The more serious the abuse, the more severe the symptoms
      that were reported. CONCLUSIONS: The study provides the first evidence from a
      controlled study that sexual abuse is associated with a higher incidence of
      psychiatric and behavioural disorder in people with learning disabilities.

PMID- 14594924
TI  - Mental health of refugees.

PMID- 14594925
TI  - A new dawn for the yellow journal?

PMID- 14594926
TI  - Health care contact and suicide.

PMID- 14594927
TI  - Effect of clozapine on mortality.

PMID- 14594928
TI  - Treating maternal depression?

PMID- 14594929
TI  - Assertive outreach in Tyneside.

PMID- 14594930
TI  - Cognitive-behavioural therapy as a treatment for psychosis.

PMID- 14594931
TI  - Efficacy of antidepressant medication.

PMID- 14594932
TI  - Cognitive-behavioural therapy as a treatment for psychosis.

PMID- 14594933
TI  - Good practice in publication of clinical trial results.

PMID- 14594934
TI  - Integrity and bias in academic psychiatry.

PMID- 14594936
TI  - Chemoprevention of cancer--focusing on clinical trials.
AB  - Chemoprevention of cancer is reviewed from the viewpoints of action mechanisms
      and methodology of clinical trials in order to introduce promising agents
      discovered by in vitro and/or in vivo studies to applications in humans. The
      clinical trial procedure essentially follows the phase study which has been
      employed for chemotherapeutic drugs. Chemoprevention of bladder cancer, prostate
      cancer, gastric cancer, hepatocellular carcinoma, breast cancer, head and neck
      cancer, colorectal cancer and lung cancer is reviewed, mainly focusing on
      clinical trials. Previous clinical trials have shown the effectiveness of the
      following: polyprenoic acid (acyclic retinoid) for hepatocellular carcinoma;
      tamoxifen for breast cancer; retinoic acids for head and neck tumor; and aspirin,
      a COX-2 inhibitor, for colorectal cancer. Despite the advantageous effects of
      some of these agents, their toxic effects must also be of concern at the same
      time. For example, in a chemoprevention trial of lung cancer, beta-carotene was
      unexpectedly found to increase the risk of lung cancer among high-risk groups. It
      is also noted that large-scale clinical trials demand large research grants,
      which may not be affordable in Japan. Chemoprevention is still an emerging field
      of oncology where researchers in both basic and clinical sciences face great
      challenges.

PMID- 14594937
TI  - Comparable outcomes of radiation therapy without high-dose methotrexate for
      patients with primary central nervous system lymphoma.
AB  - BACKGROUND: The previous trials of radiotherapy conducted for primary central
      nervous system lymphoma (PCNSL) have not been successful. Therefore, we have
      investigated the clinical outcomes and the role of radiation therapy in the
      treatment of PCNSL. METHODS: Thirty-three consecutive patients with PCNSL treated
      with cranial radiotherapy (30-40 Gy whole brain plus 10-20 Gy boost) without
      administration of high-dose methotrexate were retrospectively analyzed. Nine
      patients received whole spinal irradiation (WSI) as an additional therapy. The
      median age of patients was 58 years (range: 28-78 years), and 70% showed a poor
      performance status (PS). RESULTS: The median survival time (MST) was 13 months,
      and the 5-year overall survival rate was 35%. The initial response and the number
      of tumors were significant prognostic factors, and WSI tended toward significance
      in a multivariate analysis. Four of five patients, who received prophylactic WSI,
      were 4-year survivors without a tumor relapse and none of them had tumor
      involvement in the vertebral canal. One patient developed radiation-induced brain
      necrosis, however, WSI did not seem to affect the late complications.
      CONCLUSIONS: We consider it important to reduce severe acute and late
      complications in patients qualified for receiving an aggressive therapy, and to
      explore the possible tolerable and curative treatment methods that can be used in
      order to improve the prognosis for PCNSL. Further modifications, including the
      application of WSI seem to be necessary in the management of PCNSL.

PMID- 14594938
TI  - Hyperfractionated radiation therapy for hypopharyngeal carcinoma compared with
      conventional radiation therapy: local control, laryngeal preservation and overall
      survival.
AB  - BACKGROUND: Recent randomized trials have revealed the effectiveness of
      hyperfractionated radiation therapy for treating head and neck carcinomas,
      especially in their local control. Because the hypopharynx is located near the
      larynx, increasing local control of hypopharyngeal carcinomas achieves greater
      laryngeal preservation, which is very important for patients' quality of life. In
      consideration of this, our facility adopted hyperfractionated radiation therapy
      for hypopharyngeal carcinoma in 1996. In this study we compared the results of
      this therapy with those of conventional radiation therapy. METHODS: Forty-two
      patients with hypopharyngeal carcinoma whose tumors were inoperable or who
      refused surgery were treated with curative intended radiation therapy between
      April 1975 and January 2002 at Tokyo Metropolitan Komagome Hospital. Of these
      patients, 23 were treated with hyperfractionated radiation therapy (the HF group)
      and 19 were treated with conventional fractionated radiation therapy (the CF
      group). In the HF group, the numbers of patients at each clinical stage were as
      follows: stage I, 2; stage II, 5; stage III, 6; stage IV, 10. The fraction size
      was 1.2 Gy and the mean total dose was 73.4 Gy (range, 66-79.2 Gy). In the CF
      group, the corresponding numbers were as follows: stage I, 3; stage II, 1; stage
      III, 5; stage IV, 10. The fraction size was 1.8-2.0 Gy and the mean total dose
      was 65.4 Gy (range, 60-70 Gy). RESULTS: The 3-year local control rates for the HF
      group and the CF group were 61.5 and 18.4%, respectively (P = 0.016). The 3-year
      pharyngolaryngectomy-free survival rates for the HF group and the CF group were
      64.7% and 5.3%, respectively (P = 0.0008). The 3-year overall survival rates for
      the HF group and the CF group were 69.3 and 31.6%, respectively (P = 0.075).
      CONCLUSION: This study suggests that hyperfractionated radiation therapy for
      hypopharyngeal carcinoma is promising with a better local control rate, a greater
      laryngeal preservation rate and a relatively better overall survival rate.

PMID- 14594939
TI  - Patterns of care study in Japan: analysis of patients subjected to mastectomy
      followed by radiotherapy.
AB  - BACKGROUND: Two prospective studies reported in 1997 demonstrated that
      postoperative radiotherapy after mastectomy was not only associated with a higher
      loco-regional control rate but also with a higher overall survival rate. The
      purpose of this study is to clarify the processes of care for patients undergoing
      mastectomy and postoperative radiotherapy in Japan. METHODS: A national survey
      carried out in 1998-2000, involving 79 Japanese institutions by two-stage cluster
      sampling of institutions and patients, disclosed that 1124 patients with breast
      cancer had been treated between 1995 and 1997. Mastectomy followed by
      radiotherapy was performed on 258 patients. RESULTS: The compliance rates for pre
      treatment evaluation, including history, physical examination and mammography,
      averaged approximately 50% (24-81%). The chest wall was irradiated in only 19% of
      the patients and regional node irradiation was carried out for 70-86%. Radiation
      treatment planning with the aid of computed tomography was done in only 29% of
      patients (university hospitals or cancer centers, 39%; other hospitals, 17%; P =
      0.001). Hormonal therapy was administered to 56% of the patients who showed no
      endocrine responsiveness. Non-intensive chemotherapy, which did not include the
      use of anthracycline or taxol, was used in 55% of the patients who received
      chemotherapy. CONCLUSIONS: There is room for improvement regarding some aspects
      of radiotherapy and adjuvant systemic therapies. Especially in the field of
      radiotherapy, significant differences were found among the treatment techniques
      employed in various institutions.

PMID- 14594940
TI  - Multiple (multicentric and multifocal) cancers in the ipsilateral breast with
      different histologies: profiles of chromosomal numerical abnormality.
AB  - BACKGROUND: Chromosomal numerical abnormality (CNA) is a characteristic of breast
      cancer as with other common solid cancers. Multiple mammary carcinomas are also
      sometimes encountered in the ipsilateral breast. Deciding whether they are
      multicentric (arising independently) or multifocal (of the same origin) has been
      a continued challenge to clinicians and pathologists. METHODS: We experienced two
      cases of macroscopically distinct double carcinomas in the ipsilateral breast, in
      which two cancers had a different histopathological morphology. Centromere probes
      identifying 17 different and specific centromeres were used to obtain the profile
      of CNA for each tumor, with a microwave-assisted FISH protocol. For comparison, a
      case of three lesions, two of which had the same and the other different
      histology was also studied. RESULTS: Contrary to our expectations, in spite of
      the particular difference in the histopathological picture of these tumors, the
      CNA profile was the same in one case and different in the other. The gain of
      chromosome 1 and loss of chromosome 15 are representative features shared by
      multifocal cases. On the other hand, the multiple cancers with the same histology
      had mostly the same CNA profile. CONCLUSIONS: CNA profiling is useful to identify
      the lineage of multiple breast cancers. As shown here, regardless of the
      histological features, a certain common CNA profile can define the same origin of
      some multiple cancers.

PMID- 14594941
TI  - Influence of clinical parameters on quality of life during chemotherapy in
      patients with advanced non-small cell lung cancer: application of a general
      linear model.
AB  - OBJECTIVE: The aim of this study was to determine the relative influence of
      physician-assessed clinical parameters, including non-hematological adverse
      events and performance status, on quality of life (QOL) during chemotherapy.
      METHODS: QOL questionnaires consisting of four domains (functional, physical,
      mental and psychosocial) were self-administered every week during chemotherapy by
      patients with advanced non-small cell lung cancer in two phase III clinical
      trials; 377 patients who completed the questionnaires at baseline and at least
      once during the first course of therapy were analyzed. A general linear model was
      applied, where the four domains and the clinical parameters (nausea/vomiting,
      anorexia, diarrhea, fever, peripheral neuropathy and performance status) were
      used as the response and explanatory variables, respectively. In this model, the
      multi-dimensional and longitudinal aspects of QOL data were taken into account.
      RESULTS: All four domains were significantly affected by the occurrence of
      nausea/vomiting, anorexia and diarrhea. No influence of peripheral neuropathy on
      the domains was detected. Performance status was significantly related to the
      domains (except the psychosocial domain). CONCLUSION: This study revealed, by
      examination of multi-dimensional repeated QOL data, that clinical parameters had
      significant effects on QOL in patients undergoing chemotherapy. Our findings
      suggest that supportive care to control non-hematological adverse events,
      especially gastrointestinal, could maintain overall QOL in cancer patients in an
      earlier phase of chemotherapy.

PMID- 14594942
TI  - Postoperative radiotherapy for patients with invasive cervical cancer following
      treatment with simple hysterectomy.
AB  - BACKGROUND: This study aimed to investigate the survival and complications of
      patients who received adjuvant radiotherapy for invasive cervical cancer
      following inadvertent simple hysterectomy. METHODS: From September 1992 through
      to December 1998, 54 patients who had received simple hysterectomies for benign
      lesions, but were incidentally found with invasive carcinoma of the cervix in the
      surgical specimen, were referred to our department for postoperative irradiation.
      They were categorized into two groups according to pathological findings. Group A
      consisted of 25 patients whose specimen showed microinvasion alone, with the
      depth of stromal invasion <5 mm. Group B consisted of 29 patients whose
      pathological findings included deep stromal invasion, tumor emboli in cervix,
      lymphovascular permeation, positive or close resection margin, endometrial or
      myometrial invasion and vaginal involvement. After external beam irradiation dose
      of 44 Gy in 22 fractions over 4-5 weeks to the whole pelvis, the radiation field
      was reduced to true pelvis for a further 10 Gy in five fractions. Brachytherapy
      was performed using an Ir-192 remote after-loading technique for 1-2 courses. The
      prescribed dose for each treatment was 7.5 Gy to the vaginal surface. A
      retrospective analysis was conducted to compare radiation-therapy outcomes for
      these 54 patients. RESULTS: After 37-102 months of follow-up (median, 58 months),
      47 patients were alive without evidence of disease; five patients in Group B died
      of the disease (three with distant metastasis, one with local relapse, one with
      both). Two patients died of other concurrent diseases. The 5-year actuarial
      survival (AS) and disease-free survival (DFS) rates for all patients were 88 and
      90%, respectively. The respective 5-year AS and DFS rates for Group A/B were
      95/82% (P = 0.07) and 100/83% (P = 0.03). Ten patients (18.5%) developed RTOG
      Grade 1-4 rectal complications. Five patients (9.3%) developed RTOG Grade 3-4
      bladder complications. Eight patients (14.8%) had RTOG Grade 1-4 non-rectal
      gastrointestinal complications. CONCLUSIONS: For patients with invasive cervical
      cancer following inadvertent simple hysterectomy, external beam radiotherapy
      combined with one or two fractions of intravaginal brachytherapy could achieve
      satisfactory disease control. It is recommended to select a high-risk group for
      intensive adjuvant treatment. Further optimization of the irradiation strategy is
      also imperative to decrease the incidence of complications.

PMID- 14594943
TI  - Radiologically and histologically mixed liposarcoma: a report of two biphasic
      cases.
AB  - We report two cases of liposarcomas showing biphasic patterns, radiologically and
      histologically. The first case was a 52-year-old man with a 17 x 12 cm
      intramuscular tumor in the right thigh. MR imaging revealed a mass composed of
      two components: a fat component and another soft tissue component. Histological
      diagnosis revealed mixed-type liposarcoma consisting of well-differentiated and
      myxoid liposarcoma. The second case was a 62-year-old man with a 22 x 15 cm
      intramuscular tumor in the left calf. MR imaging showed a mass composed of fat
      and non-fat components. The histological diagnosis was well-differentiated and
      pleomorphic liposarcoma.

PMID- 14594944
TI  - The novel germline mutation of hMSH2 gene in a case of a hereditary non-polyposis
      colorectal cancer (HNPCC) patient who meets the revised Amsterdam criteria.
AB  - Hereditary non-polyposis colorectal cancer (HNPCC) is a very important clinical
      entity in oncology. In order to identify HNPCC, the international diagnostic
      criteria named "Amsterdam criteria" have been used. In this report, we present a
      case of an HNPCC patient who met the revised Amsterdam criteria after the
      sequential history taking in which a novel germline mutation of hMSH2 gene was
      detected by genetic testing. The proband was a 69-year-old Japanese female who
      was admitted to our hospital with a diagnosis of advanced ascending colon cancer.
      Microsatellite instability (MSI) analysis revealed high MSI in the resected tumor
      tissue. PCR/direct sequencing analysis of the genomic DNA revealed the TTG(Leu)
      to TAG(Stop) nonsense mutation at codon 302 in exon 5 of the hMSH2 gene, which
      was considered to be a pathogenic mutation. According to the Human Mutation
      Database and International Collaborative Group on HNPCC (ICG-HNPCC) Database,
      this type of nonsense mutation is the first report in the hMSH2 gene.

PMID- 14594945
TI  - MARK4 is a novel microtubule-associated proteins/microtubule affinity-regulating
      kinase that binds to the cellular microtubule network and to centrosomes.
AB  - The MARK protein kinases were originally identified by their ability to
      phosphorylate a serine motif in the microtubule-binding domain of tau that is
      critical for microtubule binding. Here, we report the cloning and expression of a
      novel human paralog, MARK4, which shares 75% overall homology with MARK1-3 and is
      predominantly expressed in brain. Homology is most pronounced in the catalytic
      domain (90%), and MARK4 readily phosphorylates tau and the related microtubule
      associated protein 2 (MAP2) and MAP4. In contrast to the three paralogs that all
      exhibit uniform cytoplasmic localization, MARK4 colocalizes with the centrosome
      and with microtubules in cultured cells. Overexpression of MARK4 causes thinning
      out of the microtubule network, concomitant with a reorganization of microtubules
      into bundles. In line with these findings, we show that a tandem affinity
      purified MARK4 protein complex contains alpha-, beta-, and gamma-tubulin. In
      differentiated neuroblastoma cells, MARK4 is localized prominently at the tips of
      neurite-like processes. We suggest that although the four MARK/PAR-1 kinases
      might play multiple cellular roles in concert with different targets, MARK4 is
      likely to be directly involved in microtubule organization in neuronal cells and
      may contribute to the pathological phosphorylation of tau in Alzheimer's disease.

PMID- 14594946
TI  - Suppression by p38 MAP kinase inhibitors (pyridinyl imidazole compounds) of Ah
      receptor target gene activation by 2,3,7,8-tetrachlorodibenzo-p-dioxin and the
      possible mechanism.
AB  - Cytochrome P-450 1A1 (CYP1A1) is known to be induced by aromatic hydrocarbons,
      such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), through activation of the
      aryl hydrocarbon receptor (AhR). We found that p38 MAP kinase inhibitors
      (SB203580 and SB202190; 40 microm each; pyridinyl imidazole compounds) suppressed
      CYP1A1-mRNA induction by TCDD (2 nm) in mouse hepatoma Hepa-1 cells and in human
      hepatoma HepG2 cells, and also suppressed CYP1B1-mRNA induction by TCDD (2 nm) in
      human breast adenocarcinoma MCF7 cells. An analogue compound, SB202474, which
      does not inhibit p38 MAP kinase, also suppressed CYP1A1-mRNA induction by TCDD.
      Moreover, overexpression of a dominant-negative gene for p38 MAP kinase in Hepa-1
      cells did not suppress Cyp1a1 reporter gene induction by TCDD. Therefore, the
      suppression of Cyp1a1 transcription by pyridinyl imidazole compounds is not
      because of their inhibition of p38 MAP kinase activity. Because SB203580 did not
      inhibit in vitro AhR transformation by TCDD, this compound was not acting as a
      simple AhR antagonist. SB203580 decreased TCDD-induced histone acetylation levels
      in the region of the Cyp1a1 gene promoter, especially around the TATA box
      sequence. This result suggests the possibility that pyridinyl imidazole compounds
      suppress the recruitment of some co-activator that has the histone
      acetyltransferase activity necessary for CYP1A1-mRNA transcription.

PMID- 14594947
TI  - The bimodal role of filamin in controlling the architecture and mechanics of F
      actin networks.
AB  - Reconstituted actin filament networks have been used extensively to understand
      the mechanics of the actin cortex and decipher the role of actin cross-linking
      proteins in the maintenance and deformation of cell shape. However, studies of
      the mechanical role of the F-actin cross-linking protein filamin have led to
      seemingly contradictory conclusions, in part due to the use of ill-defined
      mechanical assays. Using quantitative rheological methods that avoid the pitfalls
      of previous studies, we systematically tested the complex mechanical response of
      reconstituted actin filament networks containing a wide range of filamin
      concentrations and compared the mechanical function of filamin with that of the
      cross-linking/bundling proteins alpha-actinin and fascin. At steady state and
      within a well defined linear regime of small non-destructive deformations, F
      actin solutions behave as highly dynamic networks (actin polymers are still
      sufficiently mobile to relax the stress) below the cross-linking-to-bundling
      threshold filamin concentration, and they behave as covalently cross-linked gels
      above that threshold. Under large deformations, F-actin networks soften at low
      filamin concentrations and strain-harden at high filamin concentrations. Filamin
      cross-links F-actin into networks that are more resilient, stiffer, more solid
      like, and less dynamic than alpha-actinin and fascin. These results resolve the
      controversy by showing that F-actin/filamin networks can adopt diametrically
      opposed rheological behaviors depending on the concentration in cross-linking
      proteins.

PMID- 14594948
TI  - Transforming growth factor beta1 is up-regulated by activated Raf in skeletal
      myoblasts but does not contribute to the differentiation-defective phenotype.
AB  - The Raf/MEK/MAPK signaling module elicits a strong negative impact on skeletal
      myogenesis that is reflected by a complete loss of muscle gene transcription and
      differentiation in multinucleated myocytes. Recent evidence indicates that Raf
      signaling also may contribute to myoblast cell cycle exit and cytoprotection. To
      further define the mechanisms by which Raf participates in cellular responses, a
      stable line of myoblasts expressing an estrogen receptor-Raf chimeric protein was
      created. The cells (23A2RafER(DD)) demonstrate a strict concentration-dependent
      increase in chimeric Raf protein synthesis and downstream phosphoMAPK activation.
      Initiation of low-level Raf activity in these cells augments contractile protein
      expression and myocyte fusion. By contrast, induction of high level Raf activity
      in 23A2RafER(DD) myoblasts inhibits the formation of myocytes and muscle reporter
      gene expression. Interestingly, treatment of myoblasts with conditioned medium
      isolated from Raf-repressive cells inhibits all of the aspects of myogenesis.
      Closer examination indicates that the transforming growth factor-beta(1) (TGF
      beta(1)) gene is up-regulated in Raf-repressive myoblasts. The cells also direct
      elevated levels of Smad transcriptional activity, suggesting the existence of a
      TGF-beta(1) autocrine loop. However, extinguishing the biological activity of TGF
      beta(1) does not restore the myogenic program. Our results provide evidence for
      the involvement of Raf signal transmission during myocyte formation as well as
      during inhibition of myogenesis.

PMID- 14594949
TI  - Familial hypertrophic cardiomyopathy-linked alterations in Ca2+ binding of human
      cardiac myosin regulatory light chain affect cardiac muscle contraction.
AB  - The ventricular isoform of human cardiac regulatory light chain (HCRLC) has been
      shown to be one of the sarcomeric proteins associated with familial hypertrophic
      cardiomyopathy (FHC), an autosomal dominant disease characterized by left
      ventricular and/or septal hypertrophy, myofibrillar disarray, and sudden cardiac
      death. Our recent studies have demonstrated that the properties of isolated HCRLC
      could be significantly altered by the FHC mutations and that their detrimental
      effects depend upon the specific position of the missense mutation. This report
      reveals that the Ca(2+) sensitivity of myofibrillar ATPase activity and steady
      state force development are also likely to change with the location of the
      specific FHC HCRLC mutation. The largest effect was seen for the two FHC
      mutations, N47K and R58Q, located directly in or near the single Ca(2+)-Mg(2+)
      binding site of HCRLC, which demonstrated no Ca(2+) binding compared with wild
      type and other FHC mutants (A13T, F18L, E22K, P95A). These two mutants when
      reconstituted in porcine cardiac muscle preparations increased Ca(2+) sensitivity
      of myofibrillar ATPase activity and force development. These results suggest the
      importance of the intact Ca(2+) binding site of HCRLC in the regulation of
      cardiac muscle contraction and imply its possible role in the regulatory light
      chain-linked pathogenesis of FHC.

PMID- 14594950
TI  - Possible regulation of the conventional calpain system by skeletal muscle
      specific calpain, p94/calpain 3.
AB  - p94 (also called calpain 3) is the skeletal muscle-specific calpain and is
      considered to be a "modulator protease" in various cellular processes. Analysis
      of p94 at the protein level is an urgent issue because the loss of p94 protease
      activity causes limb-girdle muscular dystrophy type 2A. In this study, we
      enzymatically characterized one alternatively spliced variant of p94, p94:exons
      6(-)15(-)16(-) (p94delta), which lacks two of the p94-specific insertion
      sequences. In contrast to p94, which has hardly been studied enzymatically due to
      its rapid, thorough, and apparently Ca(2+)-independent autolytic activity,
      p94delta was stably expressed in COS and insect cells. p94delta showed Ca(2+)
      dependent caseinolytic and autolytic activities and an inhibitor spectrum similar
      to those of the conventional calpains. However, calpastatin did not inhibit
      p94delta and is a substrate for p94delta, which is consistent with the properties
      of p94, presenting p94 as a possible regulator of the conventional calpain
      system. We also established a semi-quantitative fluorescence resonance energy
      transfer assay using the calpastatin sequence specifically to measure p94
      activity. This method detects the activity of COS-expressed p94 and p94delta,
      suggesting that it has potential to evaluate p94 activity in vivo and in the
      diagnosis of limb-girdle muscular dystrophy type 2A.

PMID- 14594951
TI  - CARMIL is a bona fide capping protein interactant.
AB  - CARMIL, also known as Acan 125, is a multidomain protein that was originally
      identified on the basis of its interaction with the Src homology 3 (SH3) domain
      of type I myosins from Acanthamoeba. In a subsequent study of CARMIL from
      Dictyostelium, pull-down assays indicated that the protein also bound capping
      protein and the Arp2/3 complex. Here we present biochemical evidence that
      Acanthamoeba CARMIL interacts tightly with capping protein. In biochemical
      preparations, CARMIL copurified extensively with two polypeptides that were shown
      by microsequencing to be the alpha- and beta-subunits of Acanthamoeba capping
      protein. The complex between CARMIL and capping protein, which is readily
      demonstratable by chemical cross-linking, can be completely dissociated by size
      exclusion chromatography at pH 5.4. Analytical ultracentrifugation, surface
      plasmon resonance and SH3 domain pull-down assays indicate that the dissociation
      constant of capping protein for CARMIL is approximately 0.4 microm or lower.
      Using CARMIL fusion proteins, the binding site for capping protein was shown to
      reside within the carboxyl-terminal, approximately 200 residue, proline-rich
      domain of CARMIL. Finally, chemical cross-linking, analytical
      ultracentrifugation, and rotary shadowed electron microscopy revealed that CARMIL
      is asymmetric and that it exists in a monomer <--> dimer equilibrium with an
      association constant of 1.0 x 10(6) m(-1). Together, these results indicate that
      CARMIL self-associates and interacts with capping protein with affinities that,
      given the cellular concentrations of the proteins ( approximately 1 and 2 microm
      for capping protein and CARMIL, respectively), indicate that both activities
      should be physiologically relevant.

PMID- 14594952
TI  - Association of villin with phosphatidylinositol 4,5-bisphosphate regulates the
      actin cytoskeleton.
AB  - Villin, an epithelial cell actin-binding protein, severs actin in vitro and in
      vivo. Previous studies report that phosphatidylinositol 4,5-bisphosphate (PIP(2))
      regulates actin severing by villin, presumably by interaction with villin.
      However, direct association of villin with PIP(2) has never been characterized.
      In this report, we presented mutational analysis to identify the PIP(2)-binding
      sites in villin. Villin (human) binds PIP(2) with a K(d) of 39.5 microm, a
      stoichiometry of 3.3, and a Hill coefficient of 1. We generated deletion mutants
      of villin lacking putative PIP(2)-binding sites and examined the impact of these
      mutations on PIP(2) binding and actin dynamics. Our analysis revealed the
      presence of three PIP(2)-binding sites, two in the amino-terminal core and one in
      the carboxyl-terminal headpiece of human villin. Synthetic peptides analogous
      with these sites confirmed the binding domains. Circular dichroism and quenching
      of intrinsic tryptophan fluorescence revealed a significant conformational change
      in these peptides ensuing in their association with PIP(2). By using site
      directed mutagenesis (arginine 138 to alanine), we demonstrated the presence of
      an identical F-actin and PIP(2)-binding site in the capping and severing domain
      of villin. In contrast, the mutants lysine 822 and 824 to alanine demonstrated
      the presence of an overlapping F-actin and PIP(2)-binding site in the actin cross
      linking domain of villin. Consistent with this observation, association of villin
      with PIP(2) inhibited the actin capping and severing functions of villin and
      enhanced the actin bundling function of villin. Our studies revealed that
      structural changes induced by association with PIP(2) could regulate the actin
      modifying functions of villin. This study provided biochemical proof of the
      functional significance of villin association with PIP(2) and identified the
      molecular mechanisms involved in the regulation of actin dynamics by villin and
      PIP(2).

PMID- 14594953
TI  - Identification and characterization of nonmuscle myosin II-C, a new member of the
      myosin II family.
AB  - A previously unrecognized nonmuscle myosin II heavy chain (NMHC II), which
      constitutes a distinct branch of the nonmuscle/smooth muscle myosin II family,
      has recently been revealed in genome data bases. We characterized the biochemical
      properties and expression patterns of this myosin. Using nucleotide probes and
      affinity-purified antibodies, we found that the distribution of NMHC II-C mRNA
      and protein (MYH14) is widespread in human and mouse organs but is quantitatively
      and qualitatively distinct from NMHC II-A and II-B. In contrast to NMHC II-A and
      II-B, the mRNA level in human fetal tissues is substantially lower than in adult
      tissues. Immunofluorescence microscopy showed distinct patterns of expression for
      all three NMHC isoforms. NMHC II-C contains an alternatively spliced exon of 24
      nucleotides in loop I at a location analogous to where a spliced exon appears in
      NMHC II-B and in the smooth muscle myosin heavy chain. However, unlike neuron
      specific expression of the NMHC II-B insert, the NMHC II-C inserted isoform has
      widespread tissue distribution. Baculovirus expression of noninserted and
      inserted NMHC II-C heavy meromyosin (HMM II-C/HMM II-C1) resulted in significant
      quantities of expressed protein (mg of protein) for HMM II-C1 but not for HMM II
      C. Functional characterization of HMM II-C1 by actin-activated MgATPase activity
      demonstrated a V(max) of 0.55 + 0.18 s(-1), which was half-maximally activated at
      an actin concentration of 16.5 + 7.2 microm. HMM II-C1 translocated actin
      filaments at a rate of 0.05 + 0.011 microm/s in the absence of tropomyosin and at
      0.072 + 0.019 microm/s in the presence of tropomyosin in an in vitro motility
      assay.

PMID- 14594955
TI  - Sulfur single-wavelength anomalous diffraction crystal structure of a pheromone
      binding protein from the honeybee Apis mellifera L.
AB  - Pheromone binding proteins (PBPs) are small helical proteins ( approximately 13
      17 kDa) present in several sensory organs from moth and other insect species.
      They are involved in the transport of pheromones from the sensillar lymph to the
      olfactory receptors. We report here the crystal structure of a PBP (Amel-ASP1)
      originating from the honey-bee (Apis mellifera) antennae and expressed as
      recombinant protein in the yeast Pichia pastoris. Crystals of Amel-ASP1 were
      obtained at pH 5.5 using the nano-drops technique of crystallization with a novel
      optimization procedure, and the structure was solved initially with the single
      wavelength anomalous diffraction technique using sulfur anomalous dispersion. The
      structure of Amel-ASP1 has been refined at 1.6-A resolution. Its fold is roughly
      similar to that of other PBP/odorant binding proteins, presenting six helices and
      three disulfide bridges. Contrary to the PBPs from Bombyx mori (Sandler, B. H.,
      Nikonova, L., Leal, W. S., and Clardy, J. (2000) Chem. Biol. 7, 143-151) and
      Leucophea maderae (Lartigue, A., Gruez, A., Spinelli, S., Riviere, S., Brossut,
      R., Tegoni, M., and Cambillau, C. (2003) J. Biol. Chem. 278, 30213-30218), the
      extended C terminus folds into the protein and forms a wall of the internal
      hydrophobic cavity. Its backbone groups establish two hydrogen bonds with a
      serendipitous ligand, n-butyl-benzene-sulfonamide, an additive used in plastics.
      This mode of binding might, however, mimic that used by one of the pheromonal
      blend components and illustrates the binding versatility of PBPs.

PMID- 14594954
TI  - Centrosomal anchoring of protein kinase C betaII by pericentrin controls
      microtubule organization, spindle function, and cytokinesis.
AB  - Location is a critical determinant in dictating the cellular function of protein
      kinase C (PKC). Scaffold proteins contribute to localization by poising PKC at
      specific intracellular sites. Using a yeast two-hybrid screen, we identified the
      centrosomal protein pericentrin as a scaffold that tethers PKC betaII to
      centrosomes. Co-immunoprecipitation studies reveal that the native proteins
      interact in cells. Co-overexpression studies show that the interaction is
      mediated by the C1A domain of PKC and a segment of pericentrin within residues
      494-593. Immunofluorescence analysis reveals that endogenous PKC betaII
      colocalizes with pericentrin at centrosomes. Disruption of this interaction by
      expression of the interacting region of pericentrin results in release of PKC
      from the centrosome, microtubule disorganization, and cytokinesis failure.
      Overexpression of this disrupting fragment has no effect in cells lacking PKC
      betaII, indicating a specific regulatory role of this isozyme in centrosome
      function. These results reveal a novel role for PKC betaII in cytokinesis and
      indicate that this function is mediated by an interaction with pericentrin at
      centrosomes.

PMID- 14594956
TI  - Treatment of hypertension in the UK: simple as ABCD?

PMID- 14594957
TI  - Vocational rehabilitation.

PMID- 14594958
TI  - Treatment for newly diagnosed hypertension: patterns of prescribing and
      antihypertensive effectiveness in the UK.
AB  - Improved practice in the management of hypertension depends on an understanding
      of existing patterns of treatment. To describe the management of newly diagnosed
      hypertension in British general practice and the effectiveness of current
      prescribing patterns we conducted a retrospective observational study using data
      from a computerized general practitioner record database (DIN-LINK). 21 024
      patients were first treated for newly diagnosed hypertension between January 1993
      and December 1997, and were followed for 4 years. Diuretics or beta-blockers were
      the most widely prescribed first-line treatments, used in 54% of patients. The
      mean continuation rate for first-line therapy was 69% at 12 months: the
      continuation rate was highest for angiotensin converting enzyme
      inhibitors/angiotensin II receptor antagonists. After 12 months of treatment the
      mean blood pressure reduction was 19/10 mmHg. Blood pressure targets were met in
      only 14% of patients. After 48 months of treatment 34% of patients had not
      improved in band of blood pressure severity. Many patients with severe
      hypertension at 12 months were still being prescribed only one drug. The lack of
      aggression in antihypertensive treatment, indicated by the low number of agents
      prescribed and the failure to achieve targets, is disappointing. Prescribing
      patterns for first-line therapy corresponded to guidelines. Continuation rates on
      first-line therapy were higher than often reported. The choice of drug for
      additions to or switches from first-line therapy had no clear pattern. Routinely
      collected computerized data could be used to support clinical governance
      activities in primary care.

PMID- 14594959
TI  - Trust and performance management in the medical marketplace.

PMID- 14594960
TI  - Intracranial aneurysm surgery and its future.

PMID- 14594961
TI  - Does laparoscopic surgery spell the end of the open surgeon?

PMID- 14594962
TI  - Telephone reminders to reduce non-attendance rate for endoscopy.
AB  - Non-attendance at clinics and endoscopy units wastes resources and lengthens
      waiting lists. In a previous study elsewhere, a substantial proportion of
      patients claimed to have forgotten their appointment. We therefore assessed the
      value of telephoning patients a week before their booked day-case endoscopy. An
      observation period of two months was followed by an intervention period of two
      months in which patients were contacted by phone and asked if they wished to come
      for their investigation. A maximum of three separate attempts were made to
      contact each patient. Patients cancelling the appointment were replaced by others
      on the reserve list. The non-attendance rate was expressed as the percentage of
      unused beds. During the observation period 56 patients were admitted and 18 beds
      were unused. During the intervention period it was possible to contact 73 of 88
      patients and 8 of these cancelled. 87 beds were available and 83 patients were
      admitted. When clerical error, overbooking and failure to replace patients were
      taken into account, the non-attendance rate declined from 23.3% during the
      observation period to 5.7% during the intervention period (P<0.05). The
      intervention seemed more effective in reducing non-attendance in outpatients
      referrals (0/48) than in general practitioner referrals (5/40).

PMID- 14594963
TI  - Mysterious dysphagia.

PMID- 14594964
TI  - An aneurysm is born.

PMID- 14594965
TI  - Aortic root replacement in pregnancy.

PMID- 14594966
TI  - Cellulitis of the right thigh, with gas.

PMID- 14594967
TI  - "Aggressive keloid": a severe variant of familial keloid scarring.

PMID- 14594968
TI  - Haemopneumothorax after fine needle aspiration of the breast.

PMID- 14594969
TI  - Periprosthetic tuberculous breast infection.

PMID- 14594970
TI  - Renal replacement therapy in a patient with phocomelia.

PMID- 14594972
TI  - Of gods and leeches: treatment of priapism in the nineteenth century.

PMID- 14594971
TI  - Rising caesarean section rates: can evolution and ecology explain some of the
      difficulties of modern childbirth?

PMID- 14594973
TI  - Jumperphagia: a woolly diagnosis.

PMID- 14594974
TI  - Thyroid function in chronic urticaria and angio-oedema.

PMID- 14594975
TI  - Cerebrovascular disease in The Count of Monte Cristo.

PMID- 14594976
TI  - Patients' understanding of anticoagulant therapy.

PMID- 14594977
TI  - Legal considerations of clinical guidelines.

PMID- 14594978
TI  - Complementary evidence.

PMID- 14594979
TI  - Medicolegal conferencing.

PMID- 14594980
TI  - Periorbital cellulitis with breast cancer.

PMID- 14594984
TI  - Recovery of the human photopic electroretinogram after bleaching exposures:
      estimation of pigment regeneration kinetics.
AB  - We used a fibre electrode in the lower conjunctival sac of the human eye to
      record the a-wave of the photopic electroretinogram elicited in response to dim
      red flashes, delivered in the presence of a rod-saturating blue background,
      before and after exposure of the eye to bright white illumination that bleached a
      significant fraction of cone photopigment. Responses were recorded from two
      normal subjects whose pupils were maximally dilated. A range of intensities of
      bleaching light were used, from 500 to 3000 photopic cd m(-2), and exposures were
      made sufficiently long in duration to achieve a steady-state bleach. In addition,
      responses were also recorded following shorter durations of exposures to the
      highest intensity (3000 cd m(-2)); these durations ranged from 5 to 60 s. The
      amplitude of the a-wave response to dim flashes was reduced following the
      exposures, with brighter or longer exposures causing greater reduction. The
      amplitude then recovered within about 4 min to the prebleach level. The
      amplitudes measured at ca 15 ms after the flash were used to derive the effective
      intensity of the flashes, thereby quantifying the fraction of photopigment
      available at the time of delivery of each flash. Recovery from all exposures in
      both subjects followed a common time course, which could be described well by a
      model of pigment kinetics based on rate-limited regeneration, where the initial
      rate of recovery following a total bleach was ca 50% of the total pigment per
      minute, and the residual pigment level for half the maximal rate was ca 20% of
      the total pigment. The same parameters, together with a fixed photosensitivity,
      could account for the steady-state pigment levels seen at each bleaching
      intensity, and also for the fraction of pigment bleached following exposures of
      different duration at the highest intensity. The dim-flash ERG thus provides a
      novel method for assessing pigment regeneration in vivo. Our finding that pigment
      regeneration follows rate-limited kinetics may explain previous reports of
      pigment regeneration deviating from first order kinetics. We present a model of
      regeneration in which the rate limit arises from a limitation in the delivery of
      11-cis-retinoid to the photoreceptor outer segments.

PMID- 14594985
TI  - Epileptiform activity in rat hippocampus strengthens excitatory synapses.
AB  - Although epileptic seizures are characterized by excessive excitation, the role
      of excitatory synaptic transmission in the induction and expression of epilepsy
      remains unclear. Here, we show that epileptiform activity strengthens excitatory
      hippocampal synapses by increasing the number of functional (RS)-alpha-amino
      3hydroxy-5methyl-4-isoxadepropionate (AMPA)-type glutamate receptors in CA3-CA1
      synapses. This form of synaptic strengthening occludes long-term potentiation
      (LTP) and enhances long-term depression (LTD), processes involved in learning and
      memory. These changes in synaptic transmission and plasticity, which are fully
      blocked with N-methyl-D-aspartate (NMDA) receptor antagonists, may underlie
      epilepsy induction and seizure-associated memory deficits.

PMID- 14594987
TI  - Mini-dystrophin restores L-type calcium currents in skeletal muscle of transgenic
      mdx mice.
AB  - L-type calcium currents (iCa) were recorded using the two-microelectrode voltage
      clamp technique in single short toe muscle fibres of three different mouse
      strains: (i) C57/SV129 wild-type mice (wt); (ii) mdx mice (an animal model for
      Duchenne muscular dystrophy; and (iii) transgenically engineered mini-dystrophin
      (MinD)-expressing mdx mice. The activation and inactivation properties of iCa
      were examined in 2- to 18-month-old animals. Ca2+ current densities at 0 mV in
      mdx fibres increased with age, but were always significantly smaller compared to
      age-matched wild-type fibres. Time-to-peak (TTP) of iCa was prolonged in mdx
      fibres compared to wt fibres. MinD fibres always showed similar TTP and current
      amplitudes compared to age-matched wt fibres. In all three genotypes, the voltage
      dependent inactivation and deactivation of iCa were similar. Intracellular
      resting calcium concentration ([Ca2+]i) and the distribution of dihydropyridine
      binding sites were also not different in young animals of all three genotypes,
      whereas iCa was markedly reduced in mdx fibres. We conclude, that dystrophin
      influences L-type Ca2+ channels via a direct or indirect linkage which may be
      disrupted in mdx mice and may be crucial for proper excitation-contraction
      coupling initiating Ca2+ release from the sarcoplasmic reticulum. This linkage
      seems to be fully restored in the presence of mini-dystrophin.

PMID- 14594988
TI  - Ovine feto-placental metabolism.
AB  - Fetal growth depends on the transplacental nutrient supply, which, in turn, is
      determined partially by the consumption and production of nutrients by the
      uteroplacental tissues. In fetal sheep, the rates of growth and umbilical glucose
      uptake decline coincidently towards term in parallel with the normal prepartum
      rise in plasma cortisol. While cortisol is known to reduce growth in fetal sheep,
      its effects on the uteroplacental handling and delivery of nutrients remain
      unknown. Hence, this study, quantified the rates of umbilical uptake and
      uteroplacental consumption of nutrients in preterm fetuses infused with cortisol
      for 5 days to mimic the prepartum cortisol surge. Umbilical uptakes of glucose
      and lactate, but not oxygen, were significantly lower in cortisol- than saline
      infused fetuses, irrespective of whether values were expressed as absolute or
      weight-specific rates. The rate of uteroplacental consumption of glucose, but not
      oxygen, was significantly higher in cortisol- than saline-infused animals.
      Absolute rates of uteroplacental lactate production were lower in cortisol
      infused animals. When all data were combined, fetal plasma cortisol levels were
      positively correlated to uteroplacental glucose consumption and inversely related
      to umbilical glucose uptake. Cortisol treatment had no apparent effect on
      placental mRNA expression for the glucose transporters, GLUT-1 and GLUT-3. The
      results demonstrate that cortisol is physiological regulator of uteroplacental
      metabolism and nutrient delivery to the sheep fetus. These observations have
      important implications for fetal growth both in late gestation and during adverse
      intrauterine conditions, which raise fetal cortisol levels earlier in gestation.

PMID- 14594993
TI  - Specificity determinants for lipids bound to beta-barrel proteins.
AB  - The family of proteins accountable for the intracellular movement of lipids is
      characterized by a 10-stranded beta-barrel that forms an internalized cavity
      varying in size and binding preferences. The loop connecting beta-strands E and F
      (the fifth and sixth strands) is the most striking conformational difference
      between adipocyte lipid binding protein (ALBP; fatty acids) and cellular retinoic
      acid binding protein type I (CRABP I). A three-residue mutation was made in wild
      type (WT)-ALBP [ALBP with a three-residue mutation (EF-ALBP)] to mimic CRABP I.
      Crystal structures of ligand-free and EF-ALBP with bound oleic acid were solved
      to resolutions of 1.5 A and 1.7 A, respectively, and compared with previous
      studies of WT-ALBP. The changes in three residues of one loop of the protein
      appear to have altered the positioning of the C18 fatty acid, as observed in the
      electron density of EF-ALBP. The crystallographic studies made it possible to
      compare the protein conformation and ligand positioning with those found in the
      WT protein. Although the cavity binding sites in both the retinoid and fatty acid
      binding proteins are irregular, the ligand atoms appear to favor a relatively
      planar region of the cavities. Preliminary chemical characterization of the
      mutant protein indicated changes in some binding properties and overall protein
      stability.

PMID- 14594989
TI  - Activation of the store-operated calcium current ICRAC can be dissociated from
      regulated exocytosis in rat basophilic leukaemia (RBL-1) cells.
AB  - In many cell types, the emptying of intracellular Ca2+ stores results in the
      opening of store-operated Ca2+ channels in the plasma membrane. However, the
      nature of the signal that couples store content to the opening of these Ca2+
      channels is unclear. One model proposes that the Ca2+ channels are initially
      stored in cytoplasmic vesicles but inserted into the plasma membrane upon store
      depletion via a regulated exocytoytic mechanism (vesicular fusion model). Using
      the whole-cell patch-clamp technique to measure the store-operated Ca2+ current
      ICRAC and the capacitance method to monitor vesicular fusion, an indicator of
      exocytosis, we have investigated the effects of interfering with regulated
      exocytosis on the ability of ICRAC to activate. We find that the recombinant
      protein alpha-SNAP1-285, an inhibitor of exocytosis in many systems, suppresses
      such fusion but has no impact on the activation of ICRAC. A variety of other
      manoeuvres that interfere with vesicle trafficking and exocytosis were also
      without effect on ICRAC. Impairing constitutive exocytosis with brefeldin A
      reduced the extent of ICRAC, but this effect was less pronounced when current
      density was considered instead. Activation of ICRAC can therefore be clearly
      dissociated from an exocytotic mechanism, a finding that is not easily
      reconcilable with the vesicular fusion model.

PMID- 14594991
TI  - Beta 2-adrenergic regulation of ciliary beat frequency in rat bronchiolar
      epithelium: potentiation by isosmotic cell shrinkage.
AB  - Single bronchiolar ciliary cells were isolated from rat lungs. The beta(2)
      adrenergic regulation of ciliary beat frequency (CBF) was studied using video
      optical microscopy. Terbutaline (a beta(2)-adrenergic agonist) increased CBF in a
      dose-dependent manner, and it also decreased the volume of the ciliary cells.
      These terbutaline actions were inhibited by a PKA inhibitor (H-89) and mimicked
      by forskolin, IBMX and DBcAMP. Ion transport inhibitors were used to
      isosmotically manipulate the volume of the terbutaline-stimulated bronchiolar
      ciliary cells. Amiloride (1 microM) and bumetanide (20 microM) potentiated cell
      shrinkage and the CBF increase, and they shifted the terbutaline dose-response
      curve to the lower-concentration side. Quinidine (500 microM), in contrast,
      increased cell volume and suppressed the CBF increase. Moreover, a KCl solution
      containing amiloride (1 microM) and strophanthidin (100 microM) increased cell
      volume and suppressed the CBF increase, and then the subsequent removal of either
      amiloride or strophanthidin decreased cell volume and further increased CBF. NPPB
      (10 microM) or glybenclamide (200 microM) had no effect on the action of
      terbutaline. Thus, in terbutaline-stimulated ciliary cells, cell shrinkage
      enhances the CBF increase; in contrast, cell swelling suppresses it. However, the
      results of direct manupulation of cell volume by applying osmotic stresses
      (hyperosmotic shrinkage or hyposmotic swelling) were the opposite of the findings
      of the isosmotic experiments: hyposmotic cell swelling enhanced the CBF increase,
      while isosmotic swelling suppressed it. These results suggest that isosmotic and
      non-isosmotic volume changes in terbutaline-stimulated bronchiolar ciliary cells
      may trigger different signalling pathways. In conclusion, terbutaline increases
      CBF and decreases the volume of rat bronchiolar ciliary cells via cAMP
      accumulation under isosmotic conditions, and the isosmotic cell shrinkage
      enhances the CBF increase by increasing cAMP sensitivity.

PMID- 14594994
TI  - Effects of phospholipid unsaturation on the bilayer nonpolar region: a molecular
      simulation study.
AB  - Molecular dynamics simulations of two monounsaturated phosphatidylcholine (PC)
      bilayers made of 1-palmitoyl-2-oleoyl-PC (POPC; cis-unsaturated) and 1-palmitoyl
      2-elaidoyl-PC (PEPC; trans-unsaturated) were carried out to investigate the
      effect of a double bond in the PC beta-chain and its conformation on the bilayer
      core. Four nanosecond trajectories were used for analyses. A fully saturated 1,2
      dimyristoyl-PC (DMPC) bilayer was used as a reference system. In agreement with
      experimental data, this study shows that properties of the PEPC bilayer are more
      similar to those of the DMPC than to the POPC bilayer. The differences between
      POPC and PEPC bilayers may be attributed to the different ranges of angles
      covered by the torsion angles beta10 and beta12 of the single bonds next to the
      double bond in the oleoyl (O) and elaidoyl (E) chains. Broader distributions of
      beta10 and beta12 in the E chain than in the O chain make the E chain more
      flexible. In effect, the packing of chains in the PEPC bilayer is similar to that
      in the DMPC bilayer, whereas that in the POPC bilayer is looser than that in the
      DMPC bilayer. The effect of the cis-double bond on torsions at the beginning of
      the O chain (beta4 and beta5) is similar to that of cholesterol on these torsions
      in a myristoyl chain.

PMID- 14594995
TI  - In vivo modulation of HDL phospholipid has opposing effects on SR-BI- and ABCA1
      mediated cholesterol efflux.
AB  - The effects of in vivo modulation of HDL phospholipid (PL) on scavenger receptor
      class BI (SR-BI)- and ATP binding cassette transporter 1 (ABCA1)-mediated efflux
      were examined by overexpressing either endothelial lipase (EL) or
      phosphatidylserine phospholipase (PS-PLA1) in human apolipoprotein A-I (apoA-I)
      transgenic mice. Overexpression of EL led to large reductions in the serum
      PL/apoA-I ratio (-60%), total cholesterol (TC; -89%), and HDL cholesterol (-91%).
      Relative to the serum before overexpression of EL, the efflux potential of the
      serum via SR-BI decreased by 90% and ABCA1-mediated efflux increased by 63%. In
      contrast to overexpression of EL, overexpression of PS-PLA1 led to increases in
      the PL/apoA-I ratio (88%), TC (78%), HDL cholesterol (57%), and HDL size. The
      efflux potential of the serum increased by 60% via SR-BI and decreased by 57% via
      ABCA1. There were significant positive correlations between SR-BI-mediated efflux
      and a number of serum parameters, including PL/apoA-I ratio, PL, TC, free
      cholesterol (FC), and HDL cholesterol. In striking contrast, the same
      correlations were seen with ABCA1-mediated efflux, but the relationships were
      inverse. In summary, in vivo modulation of HDL PL content affects ABCA1- and SR
      BI-mediated efflux in a reciprocal manner. These findings indicate that the type
      of lipase acting on HDL in vivo will determine which FC efflux pathway the HDL
      serves. Additionally, the extent of lipolysis will determine the efficiency of FC
      removal via this pathway.

PMID- 14594996
TI  - Formation of 7-dehydrocholesterol-containing membrane rafts in vitro and in vivo,
      with relevance to the Smith-Lemli-Opitz syndrome.
AB  - Smith-Lemli-Opitz syndrome (SLOS) is a recessive disease typified by 7
      dehydrocholesterol (7DHC) accumulation and depletion of cholesterol. Because
      cholesterol is a primary component of detergent-resistant membrane domains
      ("rafts"), we examined the compatibility of 7DHC with raft formation. Liposomes
      containing bovine brain phosphatidylcholine, sphingomyelin, cerebrosides, and
      either cholesterol, 7DHC, or coprostanol (the latter being incompatible with raft
      formation) were prepared. 7DHC was indistinguishable from cholesterol in its
      ability to become incorporated into membrane rafts, as judged by physical and
      chemical criteria, whereas coprostanol did not form rafts. The in vivo
      compatibility of 7DHC with raft formation was evaluated in brains of rats treated
      with trans-1,4-bis(2-dichlorobenzylamino-ethyl)cyclohexane dihydrochloride
      (AY9944), which mimics the SLOS biochemical defect. 7DHC/cholesterol ratios in
      rafts and whole brains from AY9944-treated rats were similar, indicating
      comparable efficiency of 7DHC and cholesterol incorporation into brain rafts. In
      contrast, dolichol (a nonsterol isoprenoid incompatible with raft formation) was
      greatly depleted in brain rafts relative to whole brain. Although brain raft
      fractions prepared from AY9944-treated and control rats yielded similar sterol
      protein ratios, their gel electrophoresis profiles exhibited multiple
      differences, suggesting that altered raft sterol composition perturbs raft
      protein content. These results are discussed in the context of the SLOS
      phenotype, particularly with regard to the associated central nervous system
      defects.

PMID- 14594997
TI  - Defective uptake of triglyceride-associated fatty acids in adipose tissue causes
      the SREBP-1c-mediated induction of lipogenesis.
AB  - Lipoprotein lipase (LPL) is the only known enzyme in the capillary endothelium of
      peripheral tissues that hydrolizes plasma triglycerides and provides fatty acids
      (FAs) for their subsequent tissue uptake. Previously, we demonstrated that mice
      that express LPL exclusively in muscle develop essentially normal fat mass
      despite the absence of LPL and the deprivation of nutritionally derived FAs in
      adipose tissue (AT). Using this mouse model, we now investigated the metabolic
      response to LPL deficiency in AT that enables maintenance of normal AT mass. We
      show that the rate of FA production was 1.8-fold higher in LPL-deficient AT than
      in control AT. The levels of mRNA and enzymatic activities of important enzymes
      involved in FA and triglyceride biosynthesis were induced concomitantly.
      Increased plasma glucose clearing and (14)C-deoxyglucose uptake into LPL
      deficient mouse fat pads indicated that glucose provided the carbon source for
      lipid synthesis. Leptin expression was decreased in LPL-deficient AT. Finally,
      the induction of de novo FA synthesis in LPL-deficient AT was associated with
      increased expression and processing of sterol regulatory element binding protein
      1 (SREBP-1), together with an increase in INSIG-1 expression. These results
      suggest that in the absence of LPL in AT, lipogenesis is activated through
      increased SREBP-1 expression and processing triggered by decreased availability
      of nutrition-derived FAs, elevated insulin, and low leptin levels.

PMID- 14594998
TI  - Regulated expression of apolipoprotein E by human retinal pigment epithelial
      cells.
AB  - In early age-related macular degeneration (AMD), lipid-containing deposits
      (drusen) accumulate in Bruch's membrane underlying the retinal pigment epithelium
      (RPE). Recent studies indicate that apolipoprotein E (apoE) may play a role in
      lipid trafficking in AMD. Compared with the apoE3 allele, the apoE4 and apoE2
      alleles are associated with decreased and increased risk for AMD, respectively;
      drusen contain high levels of apoE, and apoE null mice develop lipid deposits in
      Bruch's membrane similar to those observed in AMD. Primary cultures of human RPE
      cells expressing the apoE3 allele were grown on Transwell culture plates. Western
      blotting, ELISA assay, and mass spectrometry confirmed that apoE3 was secreted
      into the apical and basal chambers and that secretion was upregulated by thyroid
      hormone, 9-cis-retinoic acid, and 22(R)-hydroxycholesterol. In addition, basally
      secreted apoE associated with exogenously added HDL. These results indicate that
      apoE secretion can be regulated by specific hormones and that apoE associates
      with HDL. The findings are consistent with a role for apoE in lipid trafficking
      through Bruch's membrane and may be relevant to AMD.

PMID- 14595000
TI  - Characterization of the ceramide moieties of sphingoglycolipids from mouse brain
      by ESI-MS/MS: identification of ceramides containing sphingadienine.
AB  - Sphingoglycolipids (SGLs) are cell membrane constituents. As the ceramide
      structure influences the biological properties of the SGL, we characterized by
      electrospray ionization tandem mass spectrometry the molecular species of
      ceramides present in SGL of mouse brain. We report here for the first time the
      presence in mammalian brain of sphingadienine (d18:2). Sphingenine (d18:1) is
      present in all SGL species, in contrast to eicosasphingenine (d20:1), which is a
      constituent of only gangliosides. Sphingadienine is present in galactosylceramide
      and sulfatides. Free ceramides contain the three types of bases. Thus, there
      could be two separate pools of free ceramides (d18:1, d18:2 and d20:1, d18:1) as
      precursors of complex SGL.

PMID- 14594999
TI  - Stimulation of cardiac cardiolipin biosynthesis by PPARalpha activation.
AB  - The role of peroxisome proliferator-activated receptor alpha (PPARalpha)
      stimulated phospholipase A2 (PLA2) in cardiac mitochondrial cardiolipin (CL)
      biosynthesis was examined in both in vivo and in vitro models. Treatment of rat
      heart H9c2 cells with clofibrate increased the expression and activity of 14 kDa
      PLA2 but did not affect the pool size of CL. Clofibrate treatment stimulated de
      novo CL biosynthesis via an increase in phosphatidylglycerolphosphate (PGP)
      synthase activity, accounting for the unaltered CL content. Cardiac PLA2, PGP
      synthase, and CDP-1,2-diacyl-sn-glycerol synthase (CDS-2) activities and CDS-2
      mRNA levels were elevated in mice fed clofibrate for 14 days compared with
      controls. In PPARalpha-null mice, clofibrate feeding did not alter cardiac PLA2,
      PGP synthase activities, or CDS-2 activity and mRNA level, confirming that these
      enzymes are regulated by PPARalpha activation. In contrast to mouse heart,
      clofibrate treatment did not affect the activity or mRNA levels of CDS-2 in H9c2
      cells, indicating that CDS-2 is regulated differently in rat heart H9c2 cells in
      vitro and in mouse heart in vivo. These results clearly indicate that cardiac CL
      de novo biosynthesis is stimulated by PPARalpha activation in responsive rodent
      models and that CDS-2 is an example of an enzyme that exhibits alternative
      regulation in vivo and in cultured cell lines. This study is the first to
      demonstrate that CL de novo biosynthesis is regulated by PPARalpha activation.

PMID- 14595001
TI  - Molecular characterization of rabbit scavenger receptor class B types I and II:
      portal to central vein gradient of expression in the liver.
AB  - To further elucidate the role of scavenger receptor class B type I (SR-BI) in
      reverse cholesterol transport and in atherogenesis, we performed studies in the
      rabbit, an animal model displaying a lipoprotein profile similar to that of
      human, expressing cholesteryl ester transfer protein in plasma and having been
      demonstrated to be susceptible to atherosclerosis. In this report, we describe
      for the first time the isolation and characterization of rabbit cDNA fragments
      encoding SR-BI and scavenger receptor class B type II (SR-BII). Development of an
      isoform-specific Taqman Real Time PCR system and generation of isoform-specific
      polyclonal antibodies allowed us to measure SR-BI and SR-BII expression in
      various rabbit organs on mRNA and protein levels, respectively. We found the
      highest expression of SR-BI in adrenal gland, liver, and proximal intestine;
      lesser expression was found in appendix and spleen. Immunohistochemical staining
      of frozen sections showed SR-BI expression in the cortex but not in the medulla
      of adrenal gland. An increasing portal to central vein gradient of expression was
      found within the hepatic lobule. As shown in this report, identification and
      characterization of SR-BI expression in the rabbit affords a powerful tool to
      elucidate the role of SR-BI in cholesterol homeostasis and atherogenesis in
      human.

PMID- 14595002
TI  - Influence of apoA-I and apoE on the formation of serum amyloid A-containing
      lipoproteins in vivo and in vitro.
AB  - Serum amyloid A (SAA) circulates bound to HDL3 during the acute-phase response
      (APR), and recent evidence suggests that elevated levels of SAA may be a risk
      factor for cardiovascular disease. In this study, SAA-HDL was produced in vivo
      during the APR and without the APR by injection of an adenoviral vector
      expressing human SAA-1. SAA-HDL was also produced in vitro by incubating mouse
      HDL with recombinant mouse SAA and by SAA-expressing cultured hepatoma cells.
      Whether produced in vivo or in vitro, SAA-HDL floated at a density corresponding
      to that of human HDL3 (d 1.12 g/ml) separate from other apolipoproteins,
      including apolipoprotein A-I (apoA-I; d 1.10 g/ml) when either apoA-I or
      apolipoprotein E (apoE) was present. In the absence of both apoA-I and apoE, SAA
      was found in VLDL and LDL, with low levels in the HDL and the lipid-poor
      fractions suggesting that other HDL apolipoproteins are incapable of facilitating
      the formation of SAA-HDL. We conclude that SAA does not exist in plasma as a
      lipid-free protein. In the presence of HDL-associated apoA-I or apoE, SAA
      circulates as SAA-HDL with a density corresponding to that of human HDL3. In the
      absence of both apoA-I and apoE, SAA-HDL is not formed and SAA associates with
      any available lipoprotein.

PMID- 14595003
TI  - Nuclear lipids: key signaling effectors in the nervous system and other tissues.
AB  - Lipids have long been recognized as quantitatively minor components of the
      nucleus, where they were initially thought to have little functional importance;
      but they now command growing interest, with recognition of their diverse
      signaling and modulating properties in that organelle. This applies to the lipid
      poor compartments of the nucleoplasm as well as the relatively lipid-rich nuclear
      envelope. Phosphoglycerides and sphingomyelin, as the predominant lipids, have
      attracted the most interest among researchers, but some of the less-abundant
      lipids such as gangliosides, sphingosine, and sphingosine phosphate are now
      becoming recognized as functionally important nuclear constituents. Among recent
      advances in this emerging field are detailed findings on the metabolic enzymes
      that synthesize and catabolize nuclear lipids; the fact that these are localized
      primarily within the nucleus itself indicates considerable autonomy with respect
      to lipid metabolism. Current studies suggest several key processes involving RNA
      and DNA reactivity that are dependent on these lipid-initiated events. Neural
      cell nuclei have been the subject of such investigations, with results that
      closely parallel the more numerous studies on nuclei of extraneural cells. This
      review attempts to outline some of the major findings on nuclear lipids of
      diverse cell types; results with nonneural nuclei will hopefully provide useful
      guideposts to further studies of neural systems.

PMID- 14595004
TI  - Mononuclear phagocyte immunity and the neuropathogenesis of HIV-1 infection.
AB  - Human immunodeficiency virus type 1 (HIV-1)-associated dementia is a
      neuroinflammatory brain disorder that is fueled by viral infection and immune
      activation of brain mononuclear phagocytes (MP; macrophages and microglia). MP
      serve as a reservoir for persistent viral infection, a vehicle for viral
      dissemination throughout the brain, and a major source of neurotoxic products
      that when produced in abundance, affect neuronal function. Such neurotoxic
      substances secreted by MP lead to clinical neurological impairment (cognitive,
      behavior, and motor abnormalities), which occurs usually years after the initial
      viral infection. How HIV-1 evades the immune function characteristic for MP as a
      first line of defense, including phagocytosis and intracellular killing, is not
      well understood despite more than two decades of study. In this report, we review
      the complex role(s) played by MP in the neuropathogenesis of HIV-1 infection. The
      clinical manifestations, pathology and pathogenesis, and treatment options are
      discussed in relationship to innate and adaptive immunity. Particular emphasis is
      given to the diversity of MP functions and how it may affect the disease process
      and manifestations. New insights into disease mechanisms are provided by advances
      in enhanced magnetic resonance imaging and proteomics to identify cell movement
      and genetic profiles of disease. New therapeutic strategies are discussed based
      on current knowledge of HIV-1-associated dementia pathogenesis.

PMID- 14595005
TI  - The emergence and characterization of macrophage-tropic SIV/HIV chimeric viruses
      (SHIVs) present in CD4+ T cell-depleted rhesus monkeys.
AB  - Highly pathogenic simian immunodeficiency virus/human immunodeficiency virus type
      1 chimeric viruses (SHIVs) induce an extremely rapid, systemic, and irreversible
      depletion of CD4+ T lymphocytes following their inoculation into rhesus macaques.
      Confocal fluorescence microscopy was used to demonstrate that high levels of
      viremia in infected animals were sustained by virus-producing tissue macrophage
      (mphi) following the irreversible elimination of CD4+ T lymphocytes by highly
      pathogenic SHIVDH12R. The envelope glycoproteins carried by plasma virus in CD4
      depleted animals were found to contain specific alterations affecting the V2
      region of gp120; similar V2 changes were observed during independent monkey
      infections. The altered V2 loops contained double amino acid deletions and the
      loss of a highly conserved N-linked glycosylation site. In contrast to the
      starting highly pathogenic SHIV, which is exclusively T cell-tropic, some mphi
      phase SHIVs, bearing altered V2 regions, were able to establish spreading
      infections of cultured alveolar mphi.

PMID- 14595006
TI  - Immature macrophages derived from mouse bone marrow produce large amounts of IL
      12p40 after LPS stimulation.
AB  - Production of IL-12 is an important indicator of the macrophage's ability to
      regulate immune responses. In this study, we investigated the IL-12 production by
      macrophages in different developmental stages. To this end, macrophages were
      generated in vitro from precursors stimulated with M-CSF, GM-CSF or IL-3. Density
      separation yielded populations enriched in different maturation stages.
      Invariably, only cells banding at the 40-50% Percoll interface produced large
      amounts of IL-12p40 when stimulated with LPS, whereas only low levels of IL-12p70
      were produced. These cells represented immature macrophages, as indicated by the
      absence of precursor markers CD31/ER-MP12, Ly-6C/ER-MP20 and ER-MP58, and by the
      low level of expression of mature-cell markers like ER-HR3, scavenger receptor
      and CD11b/Mac-1. Upon further maturation, the macrophages' ability to produce IL
      12p40 decreased, coinciding with increased nitric oxide production upon LPS
      stimulation. These results show that immature macrophages produce high levels of
      IL-12p40 and thus may either contribute to IL-12p70 production or regulate it.

PMID- 14595008
TI  - Chemical communication in a post-genomic world.

PMID- 14595007
TI  - Regulation of CD18 expression on neutrophils in response to fluid shear stress.
AB  - When leukocytes adhere to endothelial cells and are exposed to fluid shear
      stresses, they often retract pseudopods and reduce their attachment. Leukocytes
      use CD18 for membrane adhesion, but the kinetics of such integrin adhesion
      molecules under fluid shear is unknown. We examine on neutrophils with confocal
      microscopy of single adherent cells and flow cytometry of cell suspensions the
      CD18 expression under fluid shear after labeling with fluorescent antibodies.
      Fluid shear causes reduction of CD18-associated immunofluorescence of
      extracellular epitopes, especially in areas of the membrane exposed to elevated
      levels of shear (1.5 dyne/cm2 maximum shear stress; 1 dyne = 10 mN). CD18 was
      also translocated over the leukocyte surface from regions of higher shear to
      lower shear and into the membrane contact areas with the substrate. We obtained
      no evidence for cytoplasmic internalization of CD18. Fluid shear (5 dyne/cm2) in
      a suspension of human leukocytes resulted in cleavage of the extracellular domain
      but not against a cytoplasmic domain of CD18. Chelation of extracellular Ca2+
      abolished the down-regulation of CD18. Cysteine protease inhibitors and a
      selective inhibitor for cathepsin B, but no blockade of other cysteine proteases
      such as cathepsin L and calpain, aminopeptidases, elastase, or
      metalloproteinases, suppressed shear-induced CD18 down-regulation. The evidence
      suggests that physiological levels of fluid shear cause release of cysteine
      protease(s) including cathepsin B, leading to cleavage of the extracellular
      domain of CD18 molecules and possible membrane detachment.

PMID- 14595009
TI  - The anthropoid status of a primate from the late middle Eocene Pondaung Formation
      (Central Myanmar): tarsal evidence.
AB  - Primate dental and postcranial remains from the Eocene Pondaung Formation
      (Myanmar) have been the subject of considerable confusion since their initial
      discoveries, and their anthropoid status has been widely debated. We report here
      a well preserved primate talus discovered in the Segyauk locality near Mogaung
      that displays derived anatomical features typical of haplorhines, notably
      anthropoids, and lacks strepsirhine synapomorphies. Linear discriminant and
      parsimony analyses indicate that the talus from Myanmar is more similar
      structurally to those of living and extinct anthropoids than to those of
      adapiforms, and its overall osteological characteristics further point to
      arboreal quadrupedalism. Regressions of talar dimensions versus body mass in
      living primates indicate that this foot bone might have belonged to
      Amphipithecus. This evidence supports hypotheses favoring anthropoid affinities
      for the large-bodied primates from Pondaung and runs contrary to the hypothesis
      that Pondaungia and Amphipithecus are strepsirhine adapiforms.

PMID- 14595010
TI  - Randomly inserted and targeted Hox/reporter fusions transcriptionally silenced in
      Polycomb mutants.
AB  - Polycomb-group (Pc-G) proteins ensure late maintenance of transcriptional
      repression outside the expression domain of target genes in flies and
      vertebrates. They act in complexes, presumably by modulating chromatin structure.
      In Drosophila, they have been found to be associated with transcriptionally
      inactive loci but seem to be present in association with actively transcribed
      promoters as well, a feature which is not yet understood. In the mouse, mutations
      in several Pc-G genes result in an often subtle, local derepression of only a
      subset of the Hox genes rostral to their expression domains. We report here that
      Hox/reporter fusion genes, either randomly integrated as transgenes or as
      insertions within endogenous loci, are transcriptionally silenced in two mouse Pc
      G-null mutants, Mel18 and rae28. Transcriptional silencing of Hox/reporter
      transgenes in Pc-G mutants was accompanied by increased DNA methylation in the
      promoter region. Gene silencing was observed at early developmental stages, long
      before Pc-G and trithorax-group proteins exert their function in maintenance of
      the Hox patterns. Although all five Hox genes tested as Hox/reporter fusions were
      silenced in the Pc-G mutants, transcription of the endogenous loci was mildly
      decreased in a subset of these Hox genes, and Hoxb1 was the most strongly
      affected. We discuss the possibilities that the observed negative effect of Pc-G
      mutations on Hox and Hox/reporter expression may reflect a positive involvement
      of the Pc-G epigenetic repressors in initial Hox gene transcription and that this
      requirement is exacerbated by the reporter insertion.

PMID- 14595011
TI  - Developmental gene regulatory network architecture across 500 million years of
      echinoderm evolution.
AB  - Evolutionary change in morphological features must depend on architectural
      reorganization of developmental gene regulatory networks (GRNs), just as true
      conservation of morphological features must imply retention of ancestral
      developmental GRN features. Key elements of the provisional GRN for embryonic
      endomesoderm development in the sea urchin are here compared with those operating
      in embryos of a distantly related echinoderm, a starfish. These animals diverged
      from their common ancestor 520-480 million years ago. Their endomesodermal fate
      maps are similar, except that sea urchins generate a skeletogenic cell lineage
      that produces a prominent skeleton lacking entirely in starfish larvae. A
      relevant set of regulatory genes was isolated from the starfish Asterina miniata,
      their expression patterns determined, and effects on the other genes of
      perturbing the expression of each were demonstrated. A three-gene feedback loop
      that is a fundamental feature of the sea urchin GRN for endoderm specification is
      found in almost identical form in the starfish: a detailed element of GRN
      architecture has been retained since the Cambrian Period in both echinoderm
      lineages. The significance of this retention is highlighted by the observation of
      numerous specific differences in the GRN connections as well. A regulatory gene
      used to drive skeletogenesis in the sea urchin is used entirely differently in
      the starfish, where it responds to endomesodermal inputs that do not affect it in
      the sea urchin embryo. Evolutionary changes in the GRNs since divergence are
      limited sharply to certain cis-regulatory elements, whereas others have persisted
      unaltered.

PMID- 14595012
TI  - A small-molecule antagonist of CXCR4 inhibits intracranial growth of primary
      brain tumors.
AB  - The vast majority of brain tumors in adults exhibit glial characteristics. Brain
      tumors in children are diverse: Many have neuronal characteristics, whereas
      others have glial features. Here we show that activation of the Gi protein
      coupled receptor CXCR4 is critical for the growth of both malignant neuronal and
      glial tumors. Systemic administration of CXCR4 antagonist AMD 3100 inhibits
      growth of intracranial glioblastoma and medulloblastoma xenografts by increasing
      apoptosis and decreasing the proliferation of tumor cells. This reflects the
      ability of AMD 3100 to reduce the activation of extracellular signal-regulated
      kinases 1 and 2 and Akt, all of which are pathways downstream of CXCR4 that
      promote survival, proliferation, and migration. These studies (i) demonstrate
      that CXCR4 is critical to the progression of diverse brain malignances and (ii)
      provide a scientific rationale for clinical evaluation of AMD 3100 in treating
      both adults and children with malignant brain tumors.

PMID- 14595013
TI  - Interaction of sensory responses with spontaneous depolarization in layer 2/3
      barrel cortex.
AB  - The rodent primary somatosensory cortex is spontaneously active in the form of
      locally synchronous membrane depolarizations (UP states) separated by quiescent
      hyperpolarized periods (DOWN states) both under anesthesia and during quiet
      wakefulness. In vivo whole-cell recordings and tetrode unit recordings were
      combined with voltage-sensitive dye imaging to analyze the relationship of the
      activity of individual pyramidal neurons in layer 2/3 to the ensemble
      spatiotemporal dynamics of the spontaneous depolarizations. These were either
      brief and localized to an area of a barrel column or occurred as propagating
      waves dependent on local glutamatergic synaptic transmission in layer 2/3.
      Spontaneous activity inhibited the sensory responses evoked by whisker
      deflection, accounting almost entirely for the large trial-to-trial variability
      of sensory-evoked postsynaptic potentials and action potentials. Subthreshold
      sensory synaptic responses evoked while a cortical area was spontaneously
      depolarized were smaller, briefer and spatially more confined. Surprisingly,
      whisker deflections evoked fewer action potentials during the spontaneous
      depolarizations despite neurons being closer to threshold. The ongoing
      spontaneous activity thus regulates the amplitude and the time-dependent spread
      of the sensory response in layer 2/3 barrel cortex.

PMID- 14595014
TI  - Distinct peptide signals in the UmuD and UmuD' subunits of UmuD/D' mediate
      tethering and substrate processing by the ClpXP protease.
AB  - The Escherichia coli UmuD' protein is a component of DNA polymerase V, an error
      prone polymerase that carries out translesion synthesis on damaged DNA templates.
      The intracellular concentration of UmuD' is strictly controlled by regulated
      transcription, by posttranslational processing of UmuD to UmuD', and by ClpXP
      degradation. UmuD' is a substrate for the ClpXP protease but must form a
      heterodimer with its unabbreviated precursor, UmuD, for efficient degradation to
      occur. Here, we show that UmuD functions as a UmuD' delivery protein for ClpXP.
      UmuD can also deliver a UmuD partner for degradation. UmuD resembles SspB, a well
      characterized substrate-delivery protein for ClpX, in that both proteins use
      related peptide motifs to bind to the N-terminal domain of ClpX, thereby
      tethering substrate complexes to ClpXP. The combined use of a weak substrate
      recognition signal and a delivery factor that tethers the substrate to the
      protease allows regulated proteolysis of UmuD/D' in the cell. Dual recognition
      strategies of this type may be a relatively common feature of intracellular
      protein turnover.

PMID- 14595015
TI  - Gene expression patterns in human embryonic stem cells and human pluripotent germ
      cell tumors.
AB  - Remarkably little is known about the transcriptional profiles of human embryonic
      stem (ES) cells or the molecular mechanisms that underlie their pluripotency. To
      identify commonalties among the transcriptional profiles of different human
      pluripotent cells and to search for clues into the genesis of human germ cell
      tumors, we compared the expression profiles of human ES cell lines, human germ
      cell tumor cell lines and tumor samples, somatic cell lines, and testicular
      tissue samples by using cDNA microarray analysis. Hierarchical cluster analysis
      of gene expression profiles showed that the five independent human ES cell lines
      clustered tightly together, reflecting highly similar expression profiles. The
      gene expression patterns of human ES cell lines showed many similarities with the
      human embryonal carcinoma cell samples and more distantly with the seminoma
      samples. We identified 895 genes that were expressed at significantly greater
      levels in human ES and embryonal carcinoma cell lines than in control samples.
      These genes are candidates for involvement in the maintenance of a pluripotent,
      undifferentiated phenotype.

PMID- 14595016
TI  - RNA interference-mediated knockdown of a GATA factor reveals a link to anautogeny
      in the mosquito Aedes aegypti.
AB  - Blood feeding tightly regulates the reproductive cycle in anautogenous
      mosquitoes. Vitellogenesis (the synthesis of yolk protein precursors) is a key
      event in the mosquito reproductive cycle and is activated in response to a blood
      meal. Before blood feeding, Aedes aegypti is in a state of reproductive arrest
      during which the yolk protein precursor genes (YPPs) are repressed. The
      regulatory region of the major YPP gene vitellogenin (Vg) has multiple GATA
      binding sites required for the high expression level of this gene. However, a
      GATA factor (AaGATAr) likely acts as a repressor, preventing activation of this
      gene before a blood meal. Here we report in vivo data confirming the role of
      AaGATAr as a repressor of the Vg gene at the state of previtellogenic arrest.
      Using an RNA interference (RNAi)-mediated technique in conjunction with the
      Sindbis viral expression system, we show that knockdown of the AaGATAr gene
      results in an increased basal level of expression of the Vg gene and an elevated
      response to the steroid hormone 20-hydroxyecdysone in mosquitoes in a state of
      arrest. These experiments have revealed a component in the molecular mechanism by
      which anautogeny is maintained in A. aegypti.

PMID- 14595019
TI  - Aqueous access pathways in subunit a of rotary ATP synthase extend to both sides
      of the membrane.
AB  - The role of subunit a in promoting proton translocation and rotary motion in the
      Escherichia coli F1Fo ATP synthase is poorly understood. In the membrane-bound Fo
      sector of the enzyme, H+ binding and release occur at Asp-61 in the middle of the
      second transmembrane helix (TMH) of subunit c. Protons are thought to reach Asp
      61 at the center of the membrane via aqueous channels formed at least in part by
      one or more of the five TMHs of subunit a. Aqueous access pathways have
      previously been mapped to surfaces of aTMH4. Here we have substituted Cys into
      the second and fifth TMHs of subunit a and carried out chemical modification with
      Ag+ and N-ethylmaleimide to define the aqueous accessibility of residues along
      these helices. Access to cAsp-61 at the center of the membrane may be mediated in
      part by Ag+-sensitive residues 248, 249, 251, and 252 in aTMH5. From the
      periplasmic surface, aqueous access to cAsp-61 may be mediated by silver
      sensitive residues 115, 116, 119, 120, 122, and 126 in aTMH2. The Ag+-sensitive
      residues in TMH2, -4, and -5 form a continuum extending from the periplasmic to
      the cytoplasmic side of the membrane. In an arrangement of helices supported by
      second-site revertant and crosslinking analyses, these residues cluster at the
      interior of a four-helix bundle formed by TMH2-5. The aqueous access pathways at
      the interior of subunit a may be gated by a swiveling of helices in this bundle,
      alternately exposing cytoplasmic and periplasmic half channels to cAsp-61 during
      the H+ transport cycle.

PMID- 14595018
TI  - A panoramic view of gene expression in the human kidney.
AB  - To gain a molecular understanding of kidney functions, we established a high
      resolution map of gene expression patterns in the human kidney. The glomerulus
      and seven different nephron segments were isolated by microdissection from fresh
      tissue specimens, and their transcriptome was characterized by using the serial
      analysis of gene expression (SAGE) method. More than 400,000 mRNA SAGE tags were
      sequenced, making it possible to detect in each structure transcripts present at
      18 copies per cell with a 95% confidence level. Expression of genes responsible
      for nephron transport and permeability properties was evidenced through
      transcripts for 119 solute carriers, 84 channels, 43 ion-transport ATPases, and
      12 claudins. Searching for differences between the transcriptomes, we found 998
      transcripts greatly varying in abundance from one nephron portion to another.
      Clustering analysis of these transcripts evidenced different extents of
      similarity between the nephron portions. Approximately 75% of the differentially
      distributed transcripts corresponded to cDNAs of known or unknown function that
      are accurately mapped in the human genome. This systematic large-scale analysis
      of individual structures of a complex human tissue reveals sets of genes
      underlying the function of well-defined nephron portions. It also provides
      quantitative expression data for a variety of genes mutated in hereditary
      diseases and helps in sorting candidate genes for renal diseases that affect
      specific portions of the human nephron.

PMID- 14595020
TI  - Normal B-1a cell development requires B cell-intrinsic NFATc1 activity.
AB  - B-1a cells, an anatomically, phenotypically, and functionally distinct subset of
      B cells that produce the bulk of natural serum IgM and much of gut-associated
      IgA, are an important component of the early response to pathogens. Because the
      induced expression of CD5, a hallmark of B-1a cells, requires a nuclear factor of
      activated T cells (NFAT)-dependent enhancer, we examined the role of NFAT
      transcription factors in B-1a development. Here we show that the B-1a compartment
      is normal in mice lacking NFATc2 but essentially absent in mice lacking NFATc1.
      Loss of NFATc1 affects both peritoneal and splenic B-1a cells. Because there is a
      loss of B-1 cells defined by markers other than CD5, NFATc1 is not required
      simply for CD5 expression on B-1a cells. Using mixed-allotype chimeras and
      retroviral-mediated gene transduction we show that the requirement for NFATc1 is
      B cell-intrinsic. We also demonstrate that NFATc1 protein expression is elevated
      approximately 5-fold in B-1a cells compared with B-2 cells. This is the first
      definitive demonstration of a B cell-intrinsic function for an NFAT family
      transcription factor.

PMID- 14595021
TI  - Essential role for RGS9 in opiate action.
AB  - Regulators of G protein signaling (RGS) are a family of proteins known to
      accelerate termination of effector stimulation after G protein receptor
      activation. RGS9-2, a brain-specific splice variant of the RGS9 gene, is highly
      enriched in striatum and also expressed at much lower levels in periaqueductal
      gray and spinal cord, structures known to mediate various actions of morphine and
      other opiates. Morphine exerts its acute rewarding and analgesic effects by
      activation of inhibitory guanine nucleotide-binding regulatory protein-coupled
      opioid receptors, whereas chronic morphine causes addiction, tolerance to its
      acute analgesic effects, and profound physical dependence by sustained activation
      of these receptors. We show here that acute morphine administration increases
      expression of RGS9-2 in NAc and the other CNS regions, whereas chronic exposure
      decreases RGS9-2 levels. Mice lacking RGS9 show enhanced behavioral responses to
      acute and chronic morphine, including a dramatic increase in morphine reward,
      increased morphine analgesia with delayed tolerance, and exacerbated morphine
      physical dependence and withdrawal. These findings establish RGS9 as a potent
      negative modulator of opiate action in vivo, and suggest that opiate-induced
      changes in RGS9 levels contribute to the behavioral and neural plasticity
      associated with chronic opiate administration.

PMID- 14595022
TI  - Cyclin-dependent kinase 5 is a mediator of dopaminergic neuron loss in a mouse
      model of Parkinson's disease.
AB  - Recent evidence indicates that cyclin-dependent kinases (CDKs, cdks) may be
      inappropriately activated in several neurodegenerative conditions. Here, we
      report that cdk5 expression and activity are elevated after administration of 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a toxin that damages the
      nigrostriatal dopaminergic pathway. Supporting the pathogenic significance of the
      cdk5 alterations are the findings that the general cdk inhibitor, flavopiridol,
      or expression of dominant-negative cdk5, and to a lesser extent dominant-negative
      cdk2, attenuates the loss of dopaminergic neurons caused by MPTP. In addition,
      CDK inhibition strategies attenuate MPTP-induced hypolocomotion and markers of
      striatal function independent of striatal dopamine. We propose that cdk5 is a key
      regulator in the degeneration of dopaminergic neurons in Parkinson's disease.

PMID- 14595023
TI  - De novo designed cyclic-peptide heme complexes.
AB  - The structural characterization of de novo designed metalloproteins together with
      determination of chemical reactivity can provide a detailed understanding of the
      relationship between protein structure and functional properties. Toward this
      goal, we have prepared a series of cyclic peptides that bind to water-soluble
      metalloporphyrins (FeIII and CoIII). Neutral and positively charged histidine
      containing peptides bind with a high affinity, whereas anionic peptides bind only
      weakly to the negatively charged metalloporphyrin. Additionally, it was found
      that the peptide becomes helical only in the presence of the metalloporphyrin. CD
      experiments confirm that the metalloporphyrin binds specific cyclic peptides with
      high affinity and with isodichroic behavior. Thermal unfolding experiments show
      that the complex has "native-like" properties. Finally, NMR spectroscopy produced
      well dispersed spectra and experimental restraints that provide a high-resolution
      solution structure of the complexed peptide.

PMID- 14595024
TI  - Pyrin binds the PSTPIP1/CD2BP1 protein, defining familial Mediterranean fever and
      PAPA syndrome as disorders in the same pathway.
AB  - Pyrin, the familial Mediterranean fever protein, is found in association with the
      cytoskeleton in myeloid/monocytic cells and modulates IL-1beta processing, NF
      kappaB activation, and apoptosis. These effects are mediated in part through
      cognate interactions with the adaptor protein ASC, which shares an N-terminal
      motif with pyrin. We sought additional upstream regulators of inflammation by
      using pyrin as the bait in yeast two-hybrid assays. We now show that proline
      serine threonine phosphatase-interacting protein [PSTPIP1, or CD2-binding protein
      1 (CD2BP1)], a tyrosine-phosphorylated protein involved in cytoskeletal
      organization, also interacts with pyrin. Recently, PSTPIP1/CD2BP1 mutations were
      shown to cause the syndrome of pyogenic arthritis, pyoderma gangrenosum, and acne
      (PAPA), a dominantly inherited autoinflammatory disorder mediated predominantly
      by granulocytes. Endogenous PSTPIP1/CD2BP1 and pyrin are coexpressed in monocytes
      and granulocytes and can be coimmunoprecipitated from THP-1 cells. The B box
      segment of pyrin was necessary and the B box/coiled-coil segment sufficient for
      this interaction, whereas the SH3 and coiled-coil domains of PSTPIP1/CD2BP1 were
      both necessary, but neither was sufficient, for pyrin binding. The Y344F
      PSTPIP1/CD2BP1 mutation, which blocks tyrosine phosphorylation, was associated
      with a marked reduction in pyrin binding in pervanadate-treated cells. PAPA
      associated A230T and E250Q PSTPIP1/CD2BP1 mutations markedly increased pyrin
      binding as assayed by immunoprecipitation and, relative to WT, these mutants were
      hyperphosphorylated when coexpressed with c-Abl kinase. Consistent with the
      hypothesis that these mutations exert a dominant-negative effect on the
      previously reported activity of pyrin, we found increased IL-1beta production by
      peripheral blood leukocytes from a clinically active PAPA patient with the A230T
      PSTPIP1/CD2BP1 mutation and in cell lines transfected with both PAPA-associated
      mutants.

PMID- 14595025
TI  - Boundary of quantum evolution under decoherence.
AB  - Relaxation effects impose fundamental limitations on our ability to coherently
      control quantum mechanical phenomena. In this article, we use principles of
      optimal control theory to establish physical limits on how closely a quantum
      mechanical system can be steered to a desired target state in the presence of
      relaxation. In particular, we explicitly compute the maximum amplitude of
      coherence or polarization that can be transferred between coupled heteronuclear
      spins in large molecules at high magnetic fields in the presence of relaxation.
      Very general decoherence mechanisms that include cross-correlated relaxation have
      been included in our analysis. We give analytical characterization for the pulse
      sequences (control laws) that achieve these physical limits and provide
      supporting experimental evidence. Exploitation of cross-correlation effects has
      recently led to the development of powerful methods in NMR spectroscopy to study
      very large biomolecules in solution. For two heteronuclear spins, we demonstrate
      with experiments that cross-correlated relaxation optimized pulse (CROP)
      sequences provide significant gains over the state-of-the-art methods. It is
      shown that despite large relaxation rates, coherence can be transferred between
      coupled spins without any loss in special cases where cross-correlated relaxation
      rates can be tuned to autocorrelated relaxation rates.

PMID- 14595026
TI  - Unifying features in protein-folding mechanisms.
AB  - We compare the folding of representative members of a protein superfamily by
      experiment and simulation to investigate common features in folding mechanisms.
      The homeodomain superfamily of three-helical, single-domain proteins exhibits a
      spectrum of folding processes that spans the complete transition from concurrent
      secondary and tertiary structure formation (nucleation-condensation mechanism) to
      sequential secondary and tertiary formation (framework mechanism). The unifying
      factor in their mechanisms is that the transition state for (un)folding is
      expanded and very native-like, with the proportion and degree of formation of
      secondary and tertiary interactions varying. There is a transition, or slide,
      from the framework to nucleation-condensation mechanism with decreasing stability
      of the secondary structure. Thus, framework and nucleation-condensation are
      different manifestations of an underlying common mechanism.

PMID- 14595027
TI  - Rescue of mutants of the tumor suppressor p53 in cancer cells by a designed
      peptide.
AB  - We designed a series of nine-residue peptides that bound to a defined site on the
      tumor suppressor p53 and stabilized it against denaturation. To test whether the
      peptides could act as chaperones and rescue the tumor-suppressing function of
      oncogenic mutants of p53 in living cells, we treated human tumor cells with the
      fluorescein-labeled peptide Fl-CDB3 (fluorescent derivative of CDB3). Before
      treatment, the mutant p53 in the cell was predominantly denatured. Fl-CDB3 was
      taken up into the cytoplasm and nucleus and induced a substantial up-regulation
      of wild-type p53 protein and representative mutants. The mutants, His-273 and His
      175 p53, adopted the active conformation, with a dramatic decrease in the
      fraction of denatured protein. In all cases, there was p53-dependent induction of
      expression of the p53 target genes mdm2, gadd45, and p21, accompanied by p53
      dependent partial restoration of apoptosis. Fl-CDB3 sensitized cancer cells that
      carried wild-type p53 to p53-dependent gamma-radiation-induced apoptosis.
      Although Fl-CDB3 did not elicit a full biological response, it did bind to and
      rescue p53 in cells and so can serve as a lead for the development of novel drugs
      for anticancer therapy.

PMID- 14595028
TI  - Invasion, competitive dominance, and resource use by exotic and native California
      grassland species.
AB  - The dynamics of invasive species may depend on their abilities to compete for
      resources and exploit disturbances relative to the abilities of native species.
      We test this hypothesis and explore its implications for the restoration of
      native ecosystems in one of the most dramatic ecological invasions worldwide, the
      replacement of native perennial grasses by exotic annual grasses and forbs in 9.2
      million hectares of California grasslands. The long-term persistence of these
      exotic annuals has been thought to imply that the exotics are superior
      competitors. However, seed-addition experiments in a southern California
      grassland revealed that native perennial species, which had lower requirements
      for deep soil water, soil nitrate, and light, were strong competitors, and they
      markedly depressed the abundance and fecundity of exotic annuals after overcoming
      recruitment limitations. Native species reinvaded exotic grasslands across
      experimentally imposed nitrogen, water, and disturbance gradients. Thus, exotic
      annuals are not superior competitors but rather may dominate because of prior
      disturbance and the low dispersal abilities and extreme current rarity of native
      perennials. If our results prove to be general, it may be feasible to restore
      native California grassland flora to at least parts of its former range.

PMID- 14595029
TI  - Endogenous neosynthesis vs. cross-presentation of viral antigens for cytotoxic T
      cell priming.
AB  - Induction of antiviral cytotoxic T lymphocytes (CTLs) has been proposed to
      require cross-presentation of viral antigens derived from infected extralymphatic
      host cells by antigen-presenting cells (APC). This postulated mechanism of cross
      priming is thought to be essential for CTL responses against viruses that do not
      infect professional APC, e.g., because of absence of the specific virus receptor.
      Here, we show for the human pathogen poliovirus that naturally nonpermissive
      murine APC acquire viral RNA in vivo independently of the cellular virus
      receptor. Uptake of poliovirus or polioviral RNA initiated neosynthesis of viral
      antigen to an extent sufficient to prime CTLs in vivo, which were detectable 2-3
      wk after infection. Our results do not only indicate that experiments studying
      cross-presentation and cross-priming by using potentially amplifiable or
      translatable materials need careful examination, but they also question the
      general biological importance of cross-presentation and cross-priming in
      antiviral CTL responses.

PMID- 14595030
TI  - Quantitative trait symmetry independent of Hsp90 buffering: distinct modes of
      genetic canalization and developmental stability.
AB  - The Hsp90 chaperone buffers development against a wide range of morphological
      changes in many organisms and in Drosophila masks the effects of hidden genetic
      variation. Theory predicts that genetic and nongenetic buffering will share
      common mechanisms. For example, it is argued that Hsp90 genetic buffering evolved
      solely as a by-product of environmental buffering, and that Hsp90 should mask
      morphological deviations from any source. To test this idea, we examined the
      effect of Hsp90 on purely nongenetic variation in phenotype, measured as
      differences between the left and right sides of several bilaterally symmetrical
      bristle and wing traits in individual flies. Consistent with previous reports,
      Hsp90 buffered the expression of rare morphogenic variants specific to particular
      genetic backgrounds. However, neither trait-by-trait nor global asymmetry was
      affected in outbred flies treated with an Hsp90 inhibitor or across a series of
      inbred genetic backgrounds from a wild population tested in isogenic F1
      heterozygotes carrying either (i) a dominant negative Hsp90 allele on a mutant
      3rd chromosome or (ii) a null P-insertion mutation, which was introgressed into
      the control genetic background on all chromosomes. By contrast, Hsp90-regulated
      trait means and significant effects of sex, temperature, and genetic background
      on trait symmetry were clearly detected. We conclude that, by maintaining the
      function of signaling proteins, Hsp90 masks variation affecting target pathways
      and traits in populations independent of purely nongenetic sources of variation,
      refuting the idea that a single Hsp90-dependent process generally controls
      genetic canalization and developmental stability.

PMID- 14595031
TI  - N-desmethylclozapine, an allosteric agonist at muscarinic 1 receptor, potentiates
      N-methyl-D-aspartate receptor activity.
AB  - The molecular and neuronal substrates conferring on clozapine its unique and
      superior efficacy in the treatment of schizophrenia remain elusive. The
      interaction of clozapine with many G protein-coupled receptors is well documented
      but less is known about its biologically active metabolite, N-desmethylclozapine.
      Recent clinical and preclinical evidences of the antipsychotic activity of the
      muscarinic agonist xanomeline prompted us to investigate the effects of N
      desmethylclozapine on cloned human M1-M5 muscarinic receptors. N
      desmethylclozapine preferentially bound to M1 muscarinic receptors with an IC50
      of 55 nM and was a more potent partial agonist (EC50, 115 nM and 50% of
      acetylcholine response) at this receptor than clozapine. Furthermore,
      pharmacological and site-directed mutagenesis studies suggested that N
      desmethylclozapine preferentially activated M1 receptors by interacting with a
      site that does not fully overlap with the acetylcholine orthosteric site. As
      hypofunction of N-methyl-d-aspartate (NMDA) receptor-driven neuronal ensembles
      has been implicated in psychotic disorders, the neuronal activity of N
      desmethylclozapine was electrophysiologically investigated in hippocampal rat
      brain slices. N-desmethylclozapine was shown to dose-dependently potentiate NMDA
      receptor currents in CA1 pyramidal cells by 53% at 100 nM, an effect largely
      mediated by activation of muscarinic receptors. Altogether, our observations
      provide direct evidence that the brain penetrant metabolite N-desmethylclozapine
      is a potent, allosteric agonist at human M1 receptors and is able to potentiate
      hippocampal NMDA receptor currents through M1 receptor activation. These
      observations raise the possibility that N-desmethylclozapine contributes to
      clozapine's clinical activity in schizophrenics through modulation of both
      muscarinic and glutamatergic neurotransmission.

PMID- 14595032
TI  - An emotion-induced retrograde amnesia in humans is amygdala- and beta-adrenergic
      dependent.
AB  - The influence of emotion on human memory is associated with two contradictory
      effects in the form of either emotion-induced enhancements or decrements in
      memory. In a series of experiments involving single word presentation, we show
      that enhanced memory for emotional words is strongly coupled to decrements in
      memory for items preceding the emotional stimulus, an effect that is more
      pronounced in women. These memory effects would appear to depend on a common
      neurobiological substrate, in that enhancements and decrements are reversed by
      propranolol, a beta-adrenergic antagonist, and abolished by selective bilateral
      amygdala damage. Thus, our findings suggest that amygdala-dependent beta
      adrenergic modulation of episodic encoding has costs as well as benefits.

PMID- 14595033
TI  - Depression and suicide.

PMID- 14595034
TI  - Varicella.

PMID- 14595035
TI  - Consultation with the specialist: lymphomas.

PMID- 14595036
TI  - Index of suspicion.

PMID- 14595037
TI  - Food allergy.

PMID- 14595038
TI  - Question from the clinician: coin ingestion.

PMID- 14595039
TI  - Newborn screening by tandem mass spectrometry for medium-chain Acyl-CoA
      dehydrogenase deficiency: a cost-effectiveness analysis.
AB  - OBJECTIVE: To determine whether newborn screening by tandem mass spectrometry
      (MS/MS) for medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is cost
      effective versus not screening and to define the contributions of disease, test,
      and population parameters on the decision. METHODS: A decision-analytic Markov
      model was designed to perform cost-effectiveness and cost-utility analyses
      measuring the discounted, incremental cost per life-year saved and per quality
      adjusted life-year saved of newborn screening for MCADD compared with not
      screening. A hypothetical cohort of neonates made transitions among a set of
      health states that reflected clinical status, morbidity, and cost. Outcomes were
      estimated for time horizons of 20 and 70 years. Probabilities and costs were
      derived from a retrospective chart review of a 32-patient cohort treated over the
      past 30 years at the Children's Hospital of Philadelphia, clinical experience
      with MCADD patient management, patient-family interviews, cost surveys, state
      sources, and published studies. In addition to older patients who came to medical
      attention by symptomatic presentation, our patient group included 6 individuals
      whose MCADD had been diagnosed by supplemental newborn screening. Estimates of
      the expected net changes in costs and life expectancy for MCADD screening were
      used to compute the incremental cost-effectiveness ratios. Sensitivity analyses
      were performed on key input variables, and 95% confidence intervals (CIs) were
      computed through second-order Monte Carlo simulations. RESULTS: In our base-case
      analysis over the first 20 years of life, the cost of newborn screening for MCADD
      was approximately 11,000 dollars(2001 US dollars; 95% CI: <0-33,800 dollars) per
      life-year saved, or 5600 dollars (95% CI: <0-17,100 dollars) per quality-adjusted
      life-year saved compared with not screening. Over a 70-year horizon, the
      respective ratios were approximately 300 dollars (95% CI: <0-13,000 dollars) and
      100 dollars (95% CI: <0-6900 dollars). The results were robust when tested over
      plausible ranges for diagnostic test sensitivity and specificity, MCADD
      prevalence, asymptomatic rate, and screening cost. CONCLUSIONS: Simulation
      modeling indicates that newborn screening for MCADD reduces morbidity and
      mortality at an incremental cost below the range for accepted health care
      interventions. At the 70-year horizon, the model predicts that almost all of the
      additional costs of screening would be offset by avoided sequelae.

PMID- 14595040
TI  - Postnatal serum insulin-like growth factor I deficiency is associated with
      retinopathy of prematurity and other complications of premature birth.
AB  - OBJECTIVE: Insulin-like growth factor I (IGF-I) is necessary for normal
      development of retinal blood vessels in mice and humans. Because retinopathy of
      prematurity (ROP) is initiated by abnormal postnatal retinal development, we
      hypothesized that prolonged low IGF-I in premature infants might be a risk factor
      for ROP. DESIGN: We conducted a prospective, longitudinal study measuring serum
      IGF-I concentrations weekly in 84 premature infants from birth (postmenstrual
      ages: 24-32 weeks) until discharge from the hospital. Infants were evaluated for
      ROP and other morbidity of prematurity: bronchopulmonary dysplasia (BPD),
      intraventricular hemorrhage (IVH), and necrotizing enterocolitis (NEC). RESULTS:
      Low serum IGF-I values correlated with later development of ROP. The mean IGF-I
      +/- SEM level during postmenstrual ages 30-33 weeks was lowest with severe ROP
      (25 +/- 2.41 micro g/L), 29 +/- 1.76 micro g/L with moderate ROP, and 33 +/- 1.72
      micro g/L with no ROP. The duration of low IGF-I also correlated strongly with
      the severity of ROP. The interval from birth until serum IGF-I levels reached >33
      micro g/L was 23 +/- 2.6 days for no ROP, 44 +/- 4.8 days for moderate ROP, and
      52 +/- 7.5 days for severe ROP. Each adjusted stepwise increase of 5 micro g/L in
      mean IGF-I during postmenstrual ages 30 to 33 weeks decreased the risk of
      proliferative ROP by 45%. Other complications (NEC, BPD, IVH) were correlated
      with ROP and with low IGF-I levels. The relative risk for any morbidity (ROP,
      BPD, IVH, or NEC) was increased 2.2-fold (95% confidence interval: 1.41-3.43) if
      IGF-I was <or=33 micro g/L at 33 weeks' postmenstrual age. CONCLUSIONS: These
      results indicate that persistent low serum concentrations of IGF-I after
      premature birth are associated with later development of ROP and other
      complications of prematurity. IGF-I is at least as strong a determinant of risk
      for ROP as postmenstrual age at birth and birth weight.

PMID- 14595041
TI  - Keeping children out of hospitals: parents' and physicians' perspectives on how
      pediatric hospitalizations for ambulatory care-sensitive conditions can be
      avoided.
AB  - BACKGROUND: Avoidable hospitalization conditions (AHCs) are hospitalizations that
      potentially can be avoided with timely, appropriate outpatient care. The specific
      reasons for avoidability, and parents and physicians' perspectives on the
      proportion of actually avoidable pediatric AHCs, have not been examined
      adequately. OBJECTIVES: To identify how pediatric hospitalizations might be
      avoided, and to determine the proportion of avoidable AHCs according to parents
      and physicians of hospitalized children. METHODS: Cross-sectional survey of
      parents, primary care physicians (PCPs), and inpatient attending physicians
      (IAPs) of a consecutive series of children who were admitted with AHCs to an
      urban hospital in a 14-month period. RESULTS: The 554 hospitalized children had a
      median age of 4 years; most were poor (median annual family income: 12,000
      dollars), nonwhite (91%), and had public (73%) or no (16%) health insurance. The
      most frequent AHC diagnoses were asthma (43%), dehydration/gastroenteritis (16%),
      pneumonia (11%), seizure disorder (8%), and skin infections (8%). Only 25% of
      parents said that their child's admission was avoidable, compared with 29% of
      PCPs and 32% of IAPs. The proportion of AHC hospitalizations assessed as
      avoidable varied according to the source or combination of sources, from 13% for
      agreement among all 3 sources to 46% as identified by any 1 of the 3 sources.
      PCPs (71%) and IAPs (48%) significantly more often than parents (35%) cited
      parent/patient-related reasons for how hospitalizations could have been avoided,
      including adhering to and refilling medications, better outpatient follow-up, and
      avoiding known disease triggers. Parents (48%) significantly more often than PCPs
      (18%) and IAPs (37%) cited physician-related reasons for how hospitalizations
      could have been avoided, including better education by physicians about the
      child's condition, and better quality of care. Multivariate analyses revealed
      that an age >or=11 years, an asthma diagnosis, working poor family income, and
      having no health insurance were associated with approximately double to triple
      the odds of an avoidable hospitalization. CONCLUSIONS: The proportion of AHCs
      assessed as avoidable varies from 13% to 46%, depending on the source.
      Adolescents, children with asthma, children from working-poor families, and
      uninsured children are at greatest risk for avoidable hospitalizations. Many
      pediatric hospitalizations might be avoided if parents and children were better
      educated about the child's condition, medications, the need for follow-up care,
      and the importance of avoiding known disease triggers. Direct assessment by
      parents and physicians of hospitalized children can be an informative way to
      examine the proportion of avoidable pediatric hospitalizations and how they can
      be prevented.

PMID- 14595042
TI  - A randomized, controlled trial comparing two different continuous positive airway
      pressure systems for the successful extubation of extremely low birth weight
      infants.
AB  - OBJECTIVE: To determine whether the use of the Infant Flow continuous positive
      airway pressure (IF CPAP) system reduces the rate of extubation failure among
      extremely low birth weight (ELBW) infants (infants with birth weight <1000 g)
      when compared with conventional CPAP delivered with a conventional ventilator and
      nasal prongs. METHODS: A prospective, unmasked, randomized, controlled clinical
      trial was conducted in 162 eligible intubated ELBW infants who were hospitalized
      in 2 intensive care nurseries in Winston-Salem, North Carolina, between July 1997
      and November 2000. Successful extubation was defined as no need for reintubation
      for any reason for at least 7 days after the first extubation attempt. RESULTS:
      The individual extubation success rates were 61.9% (52 of 84) in the conventional
      CPAP group and 61.5% (48 of 78) in the IF CPAP group. There were no significant
      differences in the extubation success rate in any birth weight subset between the
      2 cohorts. The most common cause of extubation failure was apnea/bradycardia.
      Infants who were randomized to IF CPAP had fewer days on supplemental O(2) and
      shorter hospital stays. CONCLUSIONS: Extubation failure is a common problem,
      occurring in nearly 40% of ELBW infants who require mechanical ventilation. IF
      CPAP was as effective but no more effective than conventional CPAP in preventing
      extubation failure among ELBW infants. New strategies are needed to identify
      predictors of extubation success and to treat apnea/bradycardia, the most common
      cause of extubation failure, thereby reducing the likelihood of prolonged
      intubation in this high-risk cohort of premature infants.

PMID- 14595043
TI  - Safety of thimerosal-containing vaccines: a two-phased study of computerized
      health maintenance organization databases.
AB  - OBJECTIVE: To assess the possible toxicity of thimerosal-containing vaccines
      (TCVs) among infants. METHODS: A 2-phased retrospective cohort study was
      conducted using computerized health maintenance organization (HMO) databases.
      Phase I screened for associations between neurodevelopmental disorders and
      thimerosal exposure among 124 170 infants who were born during 1992 to 1999 at 2
      HMOs (A and B). In phase II, the most common disorders associated with exposure
      in phase I were reevaluated among 16 717 children who were born during 1991 to
      1997 in another HMO (C). Relative risks for neurodevelopmental disorders were
      calculated per increase of 12.5 micro g of estimated cumulative mercury exposure
      from TCVs in the first, third, and seventh months of life. RESULTS: In phase I at
      HMO A, cumulative exposure at 3 months resulted in a significant positive
      association with tics (relative risk [RR]: 1.89; 95% confidence interval [CI]:
      1.05-3.38). At HMO B, increased risks of language delay were found for cumulative
      exposure at 3 months (RR: 1.13; 95% CI: 1.01-1.27) and 7 months (RR: 1.07; 95%
      CI: 1.01-1.13). In phase II at HMO C, no significant associations were found. In
      no analyses were significant increased risks found for autism or attention
      deficit disorder. CONCLUSIONS: No consistent significant associations were found
      between TCVs and neurodevelopmental outcomes. Conflicting results were found at
      different HMOs for certain outcomes. For resolving the conflicting findings,
      studies with uniform neurodevelopmental assessments of children with a range of
      cumulative thimerosal exposures are needed.

PMID- 14595044
TI  - Hearing loss at school age in survivors of bacterial meningitis: assessment,
      incidence, and prediction.
AB  - OBJECTIVES: To establish the incidence of sensorineural hearing loss in children
      who survived non-Haemophilus influenzae type B (Hib) bacterial meningitis, to
      highlight the actual percentage whose hearing was evaluated, and to develop a
      prediction rule to identify those who are at risk of hearing loss. METHODS: In
      1999, we compiled a cohort of 628 school-aged children who were born between
      January 1986 and December 1994 and had survived non-Hib bacterial meningitis
      between January 1990 and December 1995. Presence of sensorineural hearing loss
      (>25 dB) was determined, based on information from questionnaires and medical
      records. Potential risk factors for hearing loss were obtained from medical
      records; independent predictors were identified using multivariate logistic
      regression analysis, leading to the formulation of a prediction rule. RESULTS:
      The incidence of hearing loss was 7%. The hearing of 68% of the children was
      evaluated as part of their routine follow-up after bacterial meningitis,
      resulting in the detection of 75% of the cases of hearing loss. The remaining 25%
      were detected after this follow-up had ended. Using a prediction rule based on 5
      factors-duration of symptoms before admission >2 days, absence of petechiae,
      cerebrospinal fluid glucose level <or=0.6 mmol/L, Streptococcus pneumoniae, and
      ataxia-62% of the postmeningitic children were selected as being at risk. All
      cases of hearing loss were in this at-risk group. CONCLUSIONS: Hearing loss can
      be predicted satisfactorily. When the hearing of children who are predicted to be
      at risk is tested as part of their routine follow-up, no children with hearing
      loss need be missed.

PMID- 14595045
TI  - Bedside procalcitonin and C-reactive protein tests in children with fever without
      localizing signs of infection seen in a referral center.
AB  - OBJECTIVE: To assess the value of bedside tests for predicting the occurrence of
      severe bacterial infections (SBIs) in children with fever without source.
      METHODS: We conducted a prospective study of 99 children, aged 7 days to 36
      months, who were seen for fever >38 degrees C and no localizing sign of infection
      at the emergency department of the University Children's Hospital of Geneva.
      Blood procalcitonin (PCT), C-reactive protein (CRP), and interleukin-6 (IL-6)
      values were determined using rapid tests and were compared with the total white
      blood cell (WBC) count with differential and clinical score. Specificity,
      sensitivity, predictive values, and multilevel likelihood ratios (LRs) with
      posttest probabilities of disease were calculated. RESULTS: Twenty-nine (29%)
      children received a diagnosis of having an SBI. PCT had the best sensitivity
      (93%) and negative predictive value (96%). Band count had the best specificity
      (93%), but its positive predictive value was only 38%. Multilevel LRs revealed
      that a PCT concentration <0.5 ng/mL (LR: 0.093) almost ruled out SBI (posttest
      probability of disease: 3.7%) in 54 (54%) subjects, whereas a value >2 ng/mL (LR:
      5.2) increased the probability of SBI to 68% in 19 (19%) children. For CRP,
      values <40 mg/L (LR: 0.263) and >100 mg/L (LR: 14.483) generated posttest
      probabilities for SBI of 9.7% (61 subjects) and 86.5% (14 subjects),
      respectively. For WBC count, the posttest probabilities of SBI were modestly
      changed from the pretest prevalence. CONCLUSIONS: PCT and CRP performed better
      than IL-6, WBC, and/or band count in predicting the occurrence of SBI. PCT and
      CRP bedside tests may be useful tools for emergency and private practice doctors
      and should be considered in the initial work-up of children with fever without
      source.

PMID- 14595046
TI  - Home syrup of ipecac use does not reduce emergency department use or improve
      outcome.
AB  - BACKGROUND: The usefulness of syrup of ipecac as a home treatment for poisoning
      and the need to keep it in the home has been increasingly challenged. Many poison
      centers do not recommend any use of syrup of ipecac. OBJECTIVE: To determine if
      use of syrup of ipecac in children at home is associated with reduced utilization
      of emergency department (ED) resources or improved outcome after unintended
      exposure to a pharmaceutical. DESIGN: Cohort comparison. SETTING: American
      Association of Poison Control Centers' Toxic Exposure Surveillance System
      Database. PATIENTS: Blinded data for each of the 64 US poison centers included ED
      referral recommendation rate, actual rate of ED use, actual home use of syrup of
      ipecac, and outcome. These data were derived from cases in 2000 and 2001
      involving children <6 years of age who unintentionally ingested a pharmaceutical
      agent and in which the call to a poison center came from home (752 602 children).
      OUTCOME MEASURES: Correlation between rate of home use of syrup of ipecac and
      rate of recommendation for ED referral was the primary outcome sought. Rate of
      adverse outcome was also compared. In addition, the actual ED use and home syrup
      of ipecac utilization rates at 7 specific centers were identified and compared
      with the published rates from these same centers from 1990 data to look for the
      trend in practice for this subgroup. RESULTS: Mean rate of referral to ED was 9%
      (range: 3%-18%). Mean home use of syrup of ipecac was 1.8% (range: 0.2%-14%).
      Increased home use of syrup of ipecac was not associated with referral to ED (r =
      0.18; 95% confidence interval of r = -0.06-0.41). Adverse outcome was rare: 0.6%
      (range: 0.2%-2.1%). There was no difference in referral rate or adverse outcome
      rate between 2 groups of 32 centers divided by relative syrup of ipecac use. In
      the 7 centers, ED use decreased from a mean of 13.5% in 1990 to a mean of 8.1% in
      2000-2001. Ipecac use decreased from a mean of 9.6% to 2.1%. CONCLUSIONS: This
      study suggests there is no reduction in resource utilization or improvement in
      patient outcome from the use of syrup of ipecac at home. Although these data
      cannot exclude a benefit in a very limited set of poisonings, any benefit remains
      to be proven.

PMID- 14595047
TI  - Rheumatic fever in children younger than 5 years: is the presentation different?
AB  - OBJECTIVE: To review our experience with children who presented with rheumatic
      fever (RF) before 5 years of age and to compare their presentation with that of
      older children. METHODS: The cardiology database was reviewed to identify
      patients who were younger than 5 years and had a diagnosis RF using the Jones
      criteria from January 1985 through March 2000. Patient age, sex, date and age at
      presentation, and the major Jones criteria fulfilled were noted. When carditis
      was present, its severity was judged to be moderate to severe when there was
      radiographic cardiomegaly and/or clinical congestive heart failure. The clinical
      presentation of patients who presented in the first 5 years of life were compared
      with the presentation of those whose RF was diagnosed after 5 years of age.
      Clinical findings at follow-up evaluation and echocardiographic findings both at
      presentation and at follow-up were noted for the children who were younger than 5
      years at presentation. RESULTS: Of 541 cases of RF seen from January 1985 through
      March 20000, 27 (5%) were in children who were younger than 5 years (median: 4.0
      years; range: 1.9-4.9 years). Major Jones criteria at presentation were arthritis
      in 17, carditis in 14, chorea in 3, and erythema marginatum in 3. The carditis
      was mild in 4 and moderate to severe in 10 patients. Compared with older
      children, younger children were more likely to present with moderate to severe
      carditis, arthritis without carditis or chorea, or the rash of erythema
      marginatum and were less likely to have chorea. The incidence of carditis was
      similar in the 2 groups as was the ratio of boys to girls. At follow-up (9.6 +/-
      5.6 years), 69% of younger children who presented with carditis have clinical
      rheumatic heart disease. Subclinical, echocardiographically detected valvular
      abnormalities were detected both at presentation (33% of all children with RF
      before 5 years of age) and at follow-up (55% of those who initially had
      carditis). CONCLUSIONS: Approximately 5% of children with RF were younger than 5
      years at diagnosis. Compared with older patients, children who presented before 5
      years of age were more likely to have moderate to severe carditis and to present
      with arthritis or the rash of erythema marginatum and were less likely to have
      chorea. Chronic rheumatic heart disease was common in young children who
      presented with carditis. Long-term follow-up is necessary to determine the
      outcome for young children with subclinical echocardiographic evidence of
      valvular disease.

PMID- 14595049
TI  - Adoption of reminder and recall messages for immunizations by pediatricians and
      public health clinics.
AB  - OBJECTIVE: Strong scientific evidence and national recommendations support the
      use of reminder and recall messages to improve immunization coverage rates, yet
      reports have suggested that only a minority of pediatric practices use such
      messages. Our aims were to 1) determine the proportions of pediatric practices
      and public clinics that currently use practice-based reminder or recall messages
      and routinely undergo immunization assessment efforts, 2) evaluate barriers and
      supports to implementing these practices, and 3) identify predictors of either
      current use or plans for future adoption of these practices. METHODS: This study
      combined qualitative and quantitative methods in sequential phases. In the
      qualitative phase, we conducted semistructured, open-ended interviews with a
      convenience sample of 18 clinician-administrators representing adopters and
      nonadopters of these messages in both private practices and public health
      clinics. In the subsequent quantitative phase, we mailed a structured, closed
      ended survey to national samples of randomly selected pediatricians (n = 600) and
      public clinics (n = 600). RESULTS: Response rates were 75% for pediatricians and
      77% for public clinics. Among pediatricians, 38% were conducting regular
      assessments of immunization coverage but only 16% were currently using routine
      reminder or recall messages. Among public clinics, 85% were conducting regular
      assessments and 51% were using reminder or recall messages. Among pediatricians'
      practices, the most commonly reported barriers to the adoption of reminder or
      recall messages were lack of time and funding and the inability to identify
      children at specified ages. For pediatricians' practices, the strongest
      predictors of current use of reminder or recall messages were having a champion
      who led efforts to improve immunization delivery (odds ratio: 1.85; 95%
      confidence interval: 1.08-3.18) and current use of regular immunization
      assessments (odds ratio: 2.30; 95% confidence interval: 1.33-3.84). Likewise, for
      public health clinics, having a champion to lead immunization improvement efforts
      and believing that their current system needed improvement was associated with
      current use of reminder or recall messages. CONCLUSIONS: Reminder and recall
      messages remain underused by both pediatricians and public health clinics.
      Promising strategies to promote adoption of these approaches in both the private
      and the public sectors include identifying and training champions to promote
      immunization delivery improvement efforts and helping practices develop methods
      to identify children at specific ages.

PMID- 14595048
TI  - Clinical presentation of pertussis in unvaccinated and vaccinated children in the
      first six years of life.
AB  - OBJECTIVES: Identifying the determinants of the clinical presentation of
      pertussis is important for the purposes of diagnosis, therapy, and control and
      for predicting the disease's clinical course and choosing an appropriate case
      definition for surveillance. Potential determinants include vaccination status,
      antibiotic treatment, age at diagnosis, and sex, although the available data are
      inconsistent. The objective of this study was to compare the clinical course of
      pertussis in unvaccinated and vaccinated children in a well-defined and strictly
      studied population and to identify determinants of the disease's clinical
      presentation. METHODS: The clinical presentation of pertussis was studied in
      children who participated in a randomized, controlled clinical trial of efficacy
      of acellular pertussis vaccine. The children belonged to the same birth cohort
      and were followed from infancy to 6 years of age in 3 distinct periods (stages 1,
      2, and 3). Children had received 1 of 2 three-component acellular pertussis
      vaccines produced by 2 manufacturers (diphtheria-tetanus-acellular pertussis
      from, Chiron Biocine [DTaP CB]; DTaP from SmithKline Beecham [DTaP SB]) or a
      diphtheria-tetanus vaccine only (DT; Chiron Biocine). Pertussis was confirmed
      through culture or serology. For each pertussis episode, information was
      collected on age at onset, sex, type of vaccine received, antibiotic treatment,
      culture results, duration of cough, spasmodic cough, and other symptoms. The
      simultaneous effect of potential determinants of clinical presentation of
      pertussis on the duration of cough and spasmodic cough was studied through
      analysis of variance models. RESULTS: The analysis was conducted on 788
      laboratory-confirmed cases of pertussis. The median duration of cough in DT
      recipients varied from 52 to 61 days across the 3 stages, whereas the median
      duration of cough in DTaP recipients varied from 29 to 39 days. The median
      duration of spasmodic cough varied from 20 to 45 days in DT recipients and from
      14 to 29 days in DTaP recipients. The results of the analysis of variance models
      showed that vaccination against pertussis reduced the length of cough from 3 to
      10 days and the length of spasmodic cough from 4 to 8 days. Culture-positive
      patients had a cough 11 to 22 days longer and a spasmodic cough 12 to 22 days
      longer than culture-negative patients. Children who received an antibiotic had a
      duration of cough 6 to 11 days longer and spasmodic cough 4 to 13 days longer
      than untreated patients. Girls had a duration of spasmodic cough 7 days longer
      than boys only after 3 years of age. Age was directly related to duration of
      cough, whereas it was inversely related to duration of spasmodic cough after 3
      years of age. CONCLUSIONS: Duration of cough can be greatly influenced by
      vaccination status. A positive culture for Bordetella pertussis is more
      frequently found in patients with long duration of cough, and antibiotic therapy
      may be a marker of severe disease. Gender may affect the clinical presentation of
      pertussis only after infancy. Pertussis in older children may be characterized by
      short duration of spasmodic cough. These results should be taken into account in
      the clinical evaluation of patients with suspected pertussis. Clinical case
      definitions for the purpose of surveillance based on the presence of 2 weeks of
      spasmodic cough may not be appropriate where pertussis vaccination uptake is
      high.

PMID- 14595050
TI  - Use of a telephone nursing line in a pediatric neurology clinic: one approach to
      the shortage of subspecialists.
AB  - OBJECTIVE: There are not enough pediatric neurologists to meet the many needs of
      pediatric neurology patients. The Hospital for Sick Children has responded by
      expanding the nursing role in the pediatric neurology outpatient clinic. The
      objective of this study was to examine the use of a telephone nursing line in
      this hospital-based pediatric neurology clinic. METHODS: A cross-sectional study
      was performed on all telephone call records collected during a 2-week study
      period. Each initial incoming call concerning a patient was counted as an index
      call. Associations between clinic type or diagnosis and length of telephone calls
      were assessed using the chi(2) test. RESULTS: A total of 208 index calls were
      received, generating a total of 597 incoming and outgoing calls. The most common
      clinic types were Epilepsy clinic (35.6%) and General Neurology clinic (32.7%),
      and the most common patient diagnoses were epilepsy (63.5%) and developmental
      delay (45.2%). Most patients were between the ages of 1 and <7 years (33.9%) and
      12 and <18 years (32.8%) and male (55.2%). Most calls were made by mothers
      (57.2%) to ask about medical administrative issues (28.4%) and/or symptoms
      (27.9%). Physicians were notified for 47.1% of calls; nurses were twice as likely
      to notify physicians for calls concerning new symptoms (relative risk: 2.1; 95%
      confidence interval: 1.6-2.7). Most calls required between 1 and 5 minutes
      (49.0%). Long telephone calls (>10 minutes) were strongly associated with a
      diagnosis of epilepsy. CONCLUSIONS: There is a high demand for the neurology
      nursing line in our clinic. Most telephone calls and most long telephone calls
      concerned patients with epilepsy. Nurses managed more than half of all telephone
      calls without physician assistance. Use of a nursing line can aid in the
      provision of care to complicated subspecialty patients. Additional strategies are
      needed to optimize delivery of care to high-need medical populations.

PMID- 14595051
TI  - Effectiveness of school-based telehealth care in urban and rural elementary
      schools.
AB  - OBJECTIVE: This study evaluated the quality and cost effectiveness of health care
      provided in urban and rural elementary school-based telehealth centers, using
      plain old telephone system (POTS) technology. METHODS: A telehealth school-based
      model was developed that used a full-time school nurse, half-time mental-health
      consultant, linked pediatric practice, and linked child psychiatrist via POTS
      with an electronic stethoscope; ears, nose, and throat endoscope; and otoscope.
      One rural and 1 urban center were evaluated. Providers, nurses, children, and
      parents completed satisfaction questionnaires. Providers and nurses also
      evaluated how well telemedicine supported their clinical decision making. Parents
      were asked how use of the center affected them financially and at work. RESULTS:
      Of the combined 3461 visits to school nurses at both centers, 4.3% resulted in
      150 telehealth consultations referrals; 142 (95%) were completed during the 2
      year project. The most common teleconsult diagnoses were otitis media,
      pharyngitis, dermatitis, and upper respiratory infections. Provider, nurse,
      child, and parent satisfaction all were high. Providers' and nurses' decision
      confidence scores ranged from a low of 4 to a high of 4.8 on a 5-point scale.
      Average family savings per encounter were 3.4 hours of work time (43 dollars) and
      177 dollars in emergency department or 54 dollars in physician costs. Including
      travel, savings for families ranged from 101 dollars to 224 dollars per
      encounter. Thirteen children received telepsychiatric evaluations resulting in
      diagnoses of depression and attention-deficit/hyperactivity, anxiety, and conduct
      disorders. CONCLUSIONS: Telehealth technology was effective in delivering
      pediatric acute care to children in these schools. Pediatric providers, nurses,
      parents, and children reported primary care school-based telehealth as an
      acceptable alternative to traditional health care delivery systems. The POTS
      based technology helps to make this telehealth service a cost-effective
      alternative for improving access to primary and psychiatric health care for
      underserved children.

PMID- 14595052
TI  - Streptococcus pneumoniae infections in the neonate.
AB  - OBJECTIVE: Streptococcus pneumoniae infections in the neonate (SPIN) are
      relatively unusual events (1%-11% of neonatal sepsis) but are associated with
      substantial morbidity and mortality. Previous reports suggest that invasive SPIN
      is associated with prolonged rupture of membranes, maternal colonization/illness,
      prematurity, early-onset pneumonia presentation (<72 hours), and high mortality
      (50%). The aim of this study was to review the current epidemiology and clinical
      course of SPIN. METHODS: The US Pediatric Multicenter Pneumococcal Surveillance
      Group has been prospectively monitoring S pneumoniae infections since 1993 in 8
      children's hospitals. For this report, data were gathered retrospectively from
      the charts of neonates who were 30 days of age and younger and had SPIN from
      September 1993 to February 2001. All pneumococcal isolates were sent to a central
      laboratory for serogrouping/typing and susceptibility testing. RESULTS: Twenty
      nine cases of SPIN were identified from a total of 4428 episodes of S pneumoniae
      infection in children. Sixty-six percent were male, and 55% were white; the mean
      age was 18.1 day (+/-8.2). Ninety percent of infants were >or=38 weeks'
      gestation. Two mothers had bacterial infections at delivery; 1 had S pneumoniae
      isolated from both blood and cervix, and 1 had clinical amnionitis. The primary
      diagnoses in the neonates were bacteremia (8), meningitis (8), bacteremic
      pneumonia (4), septic arthritis/osteomyelitis (1), and otitis media (8). Thirty
      percent of infants with invasive SPIN presented with leukopenia/neutropenia, but
      this did not predict poor outcome. The infecting pneumococcal serogroups were 19
      (32%); 9 (18%); 3 and 18 (11% each); 1, 6, and 14 (7% each); and 5 and 12 (3.5%
      each). Twenty-six percent of invasive neonatal infections were caused by
      serogroups 1, 3, 5, and 12, which are not contained in the heptavalent
      pneumococcal vaccine. In contrast, 6% of invasive nonneonatal disease was caused
      by these same nonvaccine serogroups. Susceptibility testing demonstrated that
      21.4% of isolates were penicillin nonsusceptible and 3.6% were ceftriaxone
      nonsusceptible. Three (14.3%) neonates with invasive SPIN died; all deaths
      occurred within 36 hours of presentation. Deaths did not appear to be related to
      pneumococcal serogroup or susceptibilities. CONCLUSIONS: Compared with previous
      studies of neonates with pneumococcal infection, this series showed that infants
      with SPIN were usually 2 to 3 weeks of age at presentation; likely to be full
      term; and ill with pneumonia, meningitis, and otitis media. This late-onset
      presentation was associated with an overall mortality rate of 10.3% (14.3% for
      invasive disease).

PMID- 14595053
TI  - Cytokine and cellular inflammatory sequence in enteroviral meningitis.
AB  - OBJECTIVE: To clarify the sequence of cytokines and inflammatory cells in
      enteroviral meningitis. METHODS: Cerebrospinal fluid (CSF) was collected from 86
      patients who received a diagnosis of enteroviral meningitis after detection of
      the enteroviral genome in the CSF using polymerase chain reaction. Twenty-one of
      86 patients had repeated lumbar punctures. Cytokine concentrations were measured
      acutely and in 32 samples collected during recovery. RESULTS: The proinflammatory
      cytokines (interleukin [IL]-6, IL-8, and interferon-gamma) were detected at
      significantly higher concentrations during the acute phase when enteroviral
      genomes were present. Proinflammatory cytokines decreased to normal levels in the
      recovery phase when enteroviral genomes disappeared. Anti-inflammatory
      concentrations (IL-10 and transforming growth factor-beta1) were significantly
      higher in the recovery phase than in the acute phase. Of the 86 CSF samples
      collected in the acute phase, 11 had no pleocytosis (<10 white blood
      cells/mm(3)). In 7 of those 11 CSF samples, IL-6 and IL-8 levels were as high as
      those in the 75 samples with pleocytosis (>or=10 white blood cells/mm(3)). Seven
      patients were considered to be in the initial stage of their illness when
      production of proinflammatory cytokines were high but leukocytes had not yet
      infiltrated the cerebrospinal cavity. CONCLUSIONS: The inflammatory process
      observed in human enteroviral meningitis is comparable with that observed in
      animal models: 1) infection induces proinflammatory cytokine production, followed
      by infiltration of white blood cells into the infected area, and 2) inflammation
      is terminated by the anti-inflammatory cytokines that are produced when pathogens
      are eliminated.

PMID- 14595054
TI  - Predictors of long-term outcome in very preterm infants: gestational age versus
      neonatal cranial ultrasound.
AB  - OBJECTIVES: To investigate the effect of gestational age at birth on the
      frequency of ultrasound-detected brain lesions in infants born at <33 weeks of
      gestation and to investigate whether the relationship between neonatal cranial
      ultrasound diagnosis and neurodevelopmental outcome at 8 years of age was
      independent of gestational age. METHODS: Eight hundred forty-seven infants born
      at <33 weeks of gestation, admitted to a single tertiary referral center between
      1983 and 1988, underwent serial neonatal cranial ultrasound. At 8 years of age
      neurodevelopmental outcome was assessed by structured neurologic examination,
      psychometric tests (Wechsler Intelligence Scale for Children), tests of
      visuomotor integration (Beery) and motor impairment (Henderson-Stott). Infants
      were subdivided into a group born at <28 weeks and a group born at between 28 and
      32 weeks. Neurodevelopmental outcome was analyzed for each ultrasound diagnosis.
      RESULTS: Hemorrhagic lesions such as germinal matrix/intraventricular hemorrhage
      and hemorrhagic parenchymal infarction were more frequent in infants born at <28
      weeks. There was no difference in the frequency of cystic periventricular
      leucomalacia between the 2 groups. When neurodevelopmental outcome for each
      ultrasound diagnosis was compared, no significant difference was found between
      the 2 gestational age groups. CONCLUSION: In the gestational age range studied,
      adverse neurodevelopmental outcome depends primarily on the type of the
      intracranial lesion rather than on gestational age.

PMID- 14595055
TI  - Entertainment television as a healthy sex educator: the impact of condom-efficacy
      information in an episode of friends.
AB  - CONTEXT: Television is often decried as a negative influence on the sexual
      attitudes and behavior of America's adolescents. However, television occasionally
      includes messages about the risks of having sex that may have a positive effect
      on youth. OBJECTIVE: To assess the impact of condom-efficacy messages in an
      episode of Friends on teens. Design, Setting, and Participants. A national sample
      of 506 adolescents 12 to 17 years old who had been regular viewers of Friends the
      previous year were surveyed by telephone shortly after the episode aired. OUTCOME
      MEASURES: Viewership of the Friends episode, recall of the condom-efficacy
      message, beliefs about condoms, self-reported change in condom knowledge, and
      discussions of condom efficacy with parents. RESULTS: At least 27% of the sample
      saw the episode, and 65% of these viewers recalled its depiction of condom
      failure resulting in pregnancy. Forty percent of the viewers watched with an
      adult. Ten percent of viewers talked to an adult about condom efficacy as a
      result of the show. Compared with other viewers, youth who talked with an adult
      were more likely to report learning about condoms from the episode and appeared
      less likely to reduce their perceptions of condom efficacy after the episode.
      CONCLUSIONS: Entertainment television can serve as a healthy sex educator and can
      work in conjunction with parents to improve adolescent sexual knowledge.

PMID- 14595056
TI  - Analgesia for children with acute abdominal pain: a survey of pediatric emergency
      physicians and pediatric surgeons.
AB  - OBJECTIVE: To evaluate the current opinion and practice of pediatric emergency
      medicine physicians (PEM) and pediatric surgeons (PS) on the use of opioid
      analgesia in children with acute abdominal pain during their evaluation in the
      emergency department. METHODS: All members of the American Academy of Pediatrics
      in the Section of Emergency Medicine and the American Pediatric Surgeons
      Association were mailed a copy of the survey. Inclusion criteria were board
      eligible or -certified PEM, or PS certified by American Board of Surgery or Royal
      College of Surgeons currently in practice whose patient population includes
      children. Information on primary patient population, years in practice, practice
      setting, willingness to provide analgesia for acute nontraumatic abdominal pain
      in children, and the factors influencing their decision were requested. Data were
      analyzed with the Student t test and chi(2) analysis. RESULTS: Of 1441 surveys
      sent, 54 were returned because of incorrect addresses. Of the 1387 presumed
      received, 702 completed surveys were returned with a response rate of 51%.
      However, of those who responded, 574 (82%) respondents met our inclusion
      criteria, and 385 (67%) were PEM and 189 (33%) were PS. Compared with PEM, more
      PS had >10 years of work experience and were in private practice. More PEM were
      willing to provide analgesia before definitive diagnosis. However, the overall
      willingness to provide analgesia was low in both groups. Among the physicians
      with <10 years of experience, there was no statistical difference between PEM and
      PS in willingness to provide analgesia. However, among the physicians with >10
      years of experience, 61% of PS were less likely to provide analgesia compared
      with 38% of the PEM (Delta = 23%; 95% confidence interval 13%, 33%). Of the 74
      PEM who made optional general comments, 64 (87%) cited disapproval by the PS as
      the main barrier in providing analgesia. CONCLUSIONS: The practice of providing
      analgesia for children with acute abdominal pain is divergent between PEM and PS.
      More experienced surgeons are less likely to provide analgesia for children with
      acute abdominal pain. The perceived disapproval of providing analgesia to
      children with acute abdominal pain by PS is a barrier influencing PEM practice.

PMID- 14595057
TI  - Intervention with parental smokers in an outpatient pediatric clinic using
      counseling and nicotine replacement.
AB  - OBJECTIVE: To evaluate the feasibility of implementing a smoking cessation
      intervention for parents at the time of the pediatric visit. METHODS: A
      prospective cohort of smoking parents whose child was seen in an outpatient
      pediatric practice was offered the Stop Tobacco Outreach Program, which includes
      3 brief counseling sessions, written materials, free nicotine replacement therapy
      (NRT), proactive referral to a free state telephone quitline, and fax referral to
      the parents' primary clinician. The primary outcome was completion of all three
      counseling sessions. Other outcomes were quit attempts, cessation, NRT use, state
      quitline use, and household smoking assessed at 2-month follow-up. RESULTS: One
      hundred fifty-eight smoking parents met eligibility criteria and 100 (63%)
      enrolled in the study. Of the 100 enrollees, 81% completed all three counseling
      sessions and 78% accepted free NRT at the time of enrollment. At 2-month follow
      up, of the 100 enrollees, 56% reported making a quit attempt of >or=24 hours, 18%
      reported 7-day tobacco abstinence, 34% used NRT, and 42% received additional
      counseling from the state telephone quitline. The mean number of cigarettes
      smoked inside the home and car declined over 2 months (home, 5.1 vs 1.4; and car,
      2.5 vs 1.4). CONCLUSIONS: This study demonstrates the feasibility of engaging
      parents in a smoking cessation intervention at the time of a child's clinic
      visit. This approach may be an effective way to reach smokers who otherwise are
      unlikely to access smoking cessation interventions. High rates of program
      enrollment, use of NRT, and completion of telephone counseling in this study
      support the hypothesis that a child's clinic visit is a teachable moment to
      address parental smoking cessation.

PMID- 14595058
TI  - Dysfunctional elimination syndrome: is it related to urinary tract infection or
      vesicoureteral reflux diagnosed early in life?
AB  - OBJECTIVE: It has been suggested that urinary tract infections (UTIs) early in
      life predispose to dysfunctional elimination syndrome (DES). This study evaluated
      the relationship between early UTI, vesicoureteral reflux (VUR), and DES by
      comparing two cohorts of school-aged children. METHODS: The UTI cohort (n = 123)
      included children previously enrolled in a prospective treatment trial conducted
      between 1992 and 1997. All were diagnosed with a febrile UTI before 2 years of
      age. The comparison cohort (n = 125) included children who were evaluated for
      fever in the emergency department between 1992 and 1997, whose urine culture was
      negative. Dysfunctional elimination symptoms were compared in the two cohorts by
      having families complete a revised version of the Dysfunctional Voiding Scoring
      System. RESULTS: Completed questionnaires were received from 248 children. There
      were no significant differences in selected demographic or clinical
      characteristics between the two cohorts. DES was present in 22% and 21% of
      children with and without a history of early UTI, respectively. Among children
      with UTIs, 18% of those with VUR and 25% of those without VUR had DES.
      CONCLUSIONS: Dysfunctional elimination is common in a general pediatric
      population. Neither UTI nor VUR diagnosed before 2 years of age was associated
      with DES in school-aged children.

PMID- 14595059
TI  - Association between clinically meaningful behavior problems and overweight in
      children.
AB  - OBJECTIVE: To determine whether there is a relationship between clinically
      meaningful behavior problems and concurrent and future overweight in 8- to 11
      year-old children. METHODS: 1998 National Longitudinal Survey of Youth interview
      data for 8- to 11-year-old children and their mothers were analyzed. A Behavior
      Problems Index score >90th percentile was considered clinically meaningful. Child
      overweight was defined as a body mass index (BMI) >or=95th percentile for age and
      sex. Multiple logistic regression was used to control for potential confounders
      (selected a priori): child's sex, race, use of behavior-modifying medication,
      history of academic retention, and hours of television per day; maternal obesity,
      smoking status, marital status, education, and depressive symptoms; family
      poverty status; and Home Observation for Measurement of the Environment-Short
      Form (HOME-SF) cognitive stimulation score. In an attempt to elucidate temporal
      sequence, a second analysis was conducted with a subsample of normal-weight
      children who became overweight between 1996 and 1998 while controlling for BMI z
      score in 1996. RESULTS: The sample included 755 mother-child pairs. Of the
      potential confounding variables, race, maternal obesity, academic grade
      retention, maternal education, poverty status, and HOME-SF cognitive stimulation
      score acted as joint confounders, altering the relationship between behavior
      problems and overweight in the multiple logistic regression model. With these
      covariates in the final model, behavior problems were independently associated
      with concurrent child overweight (adjusted odds ratio: 2.95; 95% confidence
      interval: 1.34-6.49). The relationship was strengthened in the subsample of
      previously normal-weight children, with race, maternal obesity, HOME-SF cognitive
      stimulation score, and 1996 BMI z score acting as confounders (adjusted odds
      ratio: 5.23; 95% confidence interval: 1.37-19.9). CONCLUSIONS: Clinically
      meaningful behavior problems in 8- to 11-year-old children were independently
      associated with an increased risk of concurrent overweight and becoming
      overweight in previously normal-weight children.

PMID- 14595060
TI  - Addressing parental smoking in pediatrics and family practice: a national survey
      of parents.
AB  - BACKGROUND: Parental smoking has been associated with increased rates of sudden
      infant death syndrome, low birth weight, otitis media, asthma, and decreased lung
      growth. No prior parent surveys have assessed national rates of screening and
      counseling for parental tobacco use in the context of their child's visit to
      primary care. OBJECTIVE: To assess and compare rates of pediatrician and family
      practitioner screening and counseling for parental smoking. Design/Methods. Data
      were collected by telephone survey of households from July to September 2001. The
      sample is weighted by race and gender based on 1999 US Census estimates to be
      representative of the US population. RESULTS: Of 3566 eligible respondents
      contacted, 3002 (84%) completed surveys; 902 of those were parents who had a
      child seen by a pediatrician (62%) or family practitioner (38%) in the past year.
      About half of all parents who visited a pediatrician or family practitioner
      reported that they had been asked about household member smoking status (52% vs
      48%). More parents who visited pediatricians had been asked if they had rules
      prohibiting smoking in the home than those who visited family practitioners (38%
      vs 29%). Of 190 (21%) parents who were smokers, fewer than half reported being
      counseled by either specialty about dangers of second-hand smoke (41% vs 33%) or
      risks of modeling smoking behavior (31% vs 28%). Similarly, fewer than half of
      parental smokers received advice to quit (36% vs 45%). CONCLUSION: Overall rates
      of screening and counseling for parental smoking in pediatric and family practice
      are low. Despite some differences between specialties, significant opportunities
      exist to improve tobacco control activities in primary care settings that serve
      children.

PMID- 14595061
TI  - Short-chain Acyl-CoA dehydrogenase deficiency: studies in a large family adding
      to the complexity of the disorder.
AB  - OBJECTIVE: To understand the expanding clinical and biochemical spectrum of short
      chain acyl-CoA dehydrogenase (SCAD) deficiency, the impact of which is not fully
      understood. STUDY DESIGN: We studied a family with SCAD deficiency and determined
      urinary ethylmalonic acid excretion, plasma C(4)-carnitine, SCAD enzyme activity
      in fibroblasts and lymphocytes, DNA mutations in the SCAD gene, and clinical
      expression. The index patient was born prematurely and had otherwise unexplained
      cholestasis and hepatomegaly during the first year of life. His mother developed
      a hemolysis-elevated liver enzymes-low platelets (HELLP) syndrome while pregnant
      with the index patient. RESULTS: Two siblings had a homozygous inactivating
      1138C>T mutation, whereas the father was compound heterozygous for this mutation
      and the common 625G>A polymorphism. There was a good correlation between the type
      of SCAD mutation, the residual SCAD enzyme activity, and the levels of urinary
      ethylmalonic acid and plasma C(4)-carnitine in each of the eight family members.
      Retrospective acylcarnitine analysis of the index patient's Guthrie screening
      card confirmed the abnormal increase of C(4)-carnitine, suggestive of SCAD
      deficiency. None of the family members had hypotonia, developmental delay, or
      episodes of ketotic hypoglycemia. CONCLUSION: Homozygosity for an inactivating
      SCAD mutation does not necessarily result in disease. The previously held opinion
      that SCAD deficiency is always a serious disorder may have been influenced by a
      clinical bias. Homozygosity for an inactivating 1138C>T SCAD mutation was
      assessed by neonatal screening of blood spot acylcarnitines. SCAD deficiency may
      be associated with maternal HELLP syndrome.

PMID- 14595063
TI  - Incorporating quality improvement into pediatric practice management.

PMID- 14595062
TI  - Effects of early childhood supplementation on the educational achievement of
      women.
AB  - OBJECTIVE: Malnutrition during early childhood has been suggested to cause
      functional disadvantages in adults, including reduced intelligence and lower
      educational achievement (EA). We assessed the effects of improved nutrition in
      early life on the EA of women in 4 rural Guatemalan villages. METHODS: The study
      sample comprised 130 female singletons exposed to either Atole (53%, 91 kcal and
      6.4 g protein/100 mL) or Fresco (47%, 33 kcal/100 mL, no protein) during the
      prenatal period and the first 2 years of life. EA was assessed at the ages of 22
      to 29 years by knowledge, numeracy, and several reading tests. A summary measure
      of EA was computed based on 5 tests, and outcome variables were categorized into
      quintiles. Analysis was based on a proportional odds model. Generalized
      estimating equations were used to account for sibling clustering. RESULTS:
      Overall, 36.2% of women completed primary school. Women exposed to Atole had
      better EA than those exposed to Fresco (odds ratio [OR]: 2.8; 95% confidence
      interval [CI], 1.4, 5.4), with a significant treatment-by-schooling interaction.
      Atole was not associated with EA (OR: 1.5; 95% CI: 0.7, 3.2) among women who did
      not complete primary school, whereas among those who completed primary school,
      Atole was associated with improved EA (OR: 13.7; 95% CI: 3.7, 50.8). CONCLUSIONS:
      We conclude that better nutrition during early childhood improved adult EA, but
      only among children who completed primary school.

PMID- 14595064
TI  - A tale of two pediatricians.

PMID- 14595066
TI  - The demise of ipecac.

PMID- 14595065
TI  - Providing services for families with a genetic condition: a contrast between
      cystic fibrosis and Down syndrome.

PMID- 14595067
TI  - Poison treatment in the home. American Academy of Pediatrics Committee on Injury,
      Violence, and Poison Prevention.
AB  - The ingestion of a potentially poisonous substance by a young child is a common
      event, with the American Association of Poison Control Centers reporting
      approximately 1.2 million such events in the United States in 2001. The American
      Academy of Pediatrics (AAP) has long concerned itself with this issue and has
      made poison prevention an integral component of its injury prevention
      initiatives. A key AAP recommendation has been to keep a 1-oz bottle of syrup of
      ipecac in the home to be used only on the advice of a physician or poison control
      center. Recently, there has been interest regarding activated charcoal in the
      home as a poison treatment strategy. After reviewing the evidence, the AAP
      believes that ipecac should no longer be used routinely as a home treatment
      strategy, that existing ipecac in the home should be disposed of safely, and that
      it is premature to recommend the administration of activated charcoal in the
      home. The first action for a caregiver of a child who may have ingested a toxic
      substance is to consult with the local poison control center.

PMID- 14595068
TI  - Consent by proxy for nonurgent pediatric care.
AB  - Minor-aged patients are often brought to the pediatrician for nonurgent acute
      medical care or health supervision visits by someone other than their custodial
      parent or guardian. These surrogates can be members of the child's extended
      family, such as a grandparent or aunt. In cases of divorce and remarriage, a
      noncustodial parent or stepparent may accompany the patient. Sometimes, children
      are brought for care by adults living in the home who are not biologically or
      legally related to the child. In some instances, a child care professional (eg,
      au pair, nanny) brings the pediatric patient for medical care. This report
      identifies common situations in which pediatricians may encounter "consent by
      proxy" for nonurgent medical care for minors and explains the potential for
      liability exposure associated with these circumstances. The report suggests
      practical steps that balance the need to minimize the physician's liability
      exposure with the patient's access to health care. Key issues to be considered
      when creating or updating office policies for obtaining and documenting consent
      by proxy are offered.

PMID- 14595069
TI  - Human milk, breastfeeding, and transmission of human immunodeficiency virus type
      1 in the United States. American Academy of Pediatrics Committee on Pediatric
      AIDS.
AB  - Transmission of human immunodeficiency virus type 1 (HIV-1) through breastfeeding
      has been conclusively demonstrated. The risk of such transmission has been
      quantified, the timing has been clarified, and certain risk factors for
      breastfeeding transmission have been identified. In areas where infant formula is
      accessible, affordable, safe, and sustainable, avoidance of breastfeeding has
      represented one of the main components of mother-to-child HIV-1 transmission
      prevention efforts for many years. In areas where affordable and safe
      alternatives to breastfeeding may not be available, interventions to prevent
      breastfeeding transmission are being investigated. Complete avoidance of
      breastfeeding by HIV-1-infected women has been recommended by the American
      Academy of Pediatrics and the Centers for Disease Control and Prevention and
      remains the only means by which prevention of breastfeeding transmission of HIV-1
      can be absolutely ensured. This technical report summarizes the information
      available regarding breastfeeding transmission of HIV-1.

PMID- 14595070
TI  - Out-of-school suspension and expulsion. American Academy of Pediatrics Committee
      on School Health.
AB  - Suspension and expulsion from school are used to punish students, alert parents,
      and protect other students and school staff. Unintended consequences of these
      practices require more attention from health care professionals. Suspension and
      expulsion may exacerbate academic deterioration, and when students are provided
      with no immediate educational alternative, student alienation, delinquency,
      crime, and substance abuse may ensue. Social, emotional, and mental health
      support for students at all times in all schools can decrease the need for
      expulsion and suspension and should be strongly advocated by the health care
      community. This policy statement, however, highlights aspects of expulsion and
      suspension that jeopardize children's health and safety. Recommendations are
      targeted at pediatricians, who can help schools address the root causes of
      behaviors that lead to suspension and expulsion and can advocate for alternative
      disciplinary policies. Pediatricians can also share responsibility with schools
      to provide students with health and social resources.

PMID- 14595071
TI  - Management of hypoplastic left heart syndrome.

PMID- 14595072
TI  - Defining asthma in the preschool-aged child.

PMID- 14595073
TI  - Neonatal jaundice coinciding with or resulting from urinary tract infections?

PMID- 14595074
TI  - Neonatal jaundice and urinary tract infections.

PMID- 14595075
TI  - Decrease in hospital admissions for febrile seizures and reports of hypotonic
      hyporesponsive episodes presenting to hospital emergency departments since
      switching to acellular pertussis vaccine in Canada: a report from IMPACT.
AB  - OBJECTIVE: Acellular pertussis vaccines were introduced with the promise of an
      improved safety profile compared with whole-cell vaccines. In 1997-1998, Canada
      adopted 1 combination acellular pertussis vaccine, having previously used 1
      particular combination whole-cell pertussis vaccine. We hypothesized that the
      change would result in a decrease in hospitalization rates for seizures and
      reports of hypotonic-hyporesponsive episodes (HHEs) temporally related to
      pertussis vaccination. METHODS: Active surveillance was performed between 1995
      and 2001 by the Immunization Monitoring Program-Active monitors at 12 hospitals
      using standard case definitions. Seizures had to occur within 72 hours after
      immunization with a pertussis-containing vaccine or 5 to 30 days after
      immunization with measles-mumps-rubella vaccine. HHE episodes had to occur within
      48 hours of receipt of a pertussis-containing vaccine. Poisson regression models
      were used to compare the average number of monthly admissions for seizures and
      HHEs before and after introduction of the acellular pertussis vaccine. RESULTS:
      We found a 79% decrease in febrile seizures associated with receipt of pertussis
      vaccine but no significant decrease in febrile seizures temporally related to
      measles-mumps-rubella between 1995-1996 and 1998-2001. There was a 60% to 67%
      reduction in HHEs associated with pertussis-containing vaccines between the same
      time periods, depending on case definition. CONCLUSIONS: The risks of febrile
      seizures and HHEs after pertussis-containing vaccine declined significantly with
      the introduction of acellular pertussis vaccine in Canada. Active surveillance
      systems are important for detecting trends in uncommon adverse events after
      routine immunizations.

PMID- 14595076
TI  - Closure of patent ductus arteriosus with oral ibuprofen suspension in premature
      newborns: a pilot study.
AB  - OBJECTIVE: Patent ductus arteriosus (PDA), a common finding among premature
      infants, is conventionally treated by intravenous indomethacin. Intravenous
      ibuprofen was recently shown to be as effective and to have fewer adverse
      reactions in preterm infants. If equally effective, then oral ibuprofen for PDA
      closure would have several important advantages over the intravenous route. This
      study was designed to determine whether oral ibuprofen treatment is efficacious
      and safe in closure of a PDA in premature infants with respiratory distress
      syndrome. METHODS: Twenty-two preterm newborns (gestational age: 27.5 +/- 1.75
      [range: 23.9-31 weeks]; weight: 979 +/- 266 [range: 380-1500 g]) with PDA and
      respiratory distress syndrome were studied prospectively. They received oral
      ibuprofen suspension 10 mg/kg/body weight for the first dose, followed at 24-hour
      intervals by 2 additional doses of 5 mg/kg each, if needed, starting on the
      second day of life. Echocardiography was performed before treatment and 24 hours
      after each dose. Every child underwent cranial ultrasonography before and after
      each ibuprofen dose. The rate of ductal closure, the need for additional
      treatment, side effects, complications, and the infants' clinical courses were
      recorded. RESULTS: Ductal closure was achieved in all newborns except for 1
      (95.5%), in whom clinically nonsignificant ductal shunting persisted. No infant
      required surgical ligation of the ductus. There was no reopening of the ductus
      after closure had been achieved. Fourteen newborns were treated with 1 dose of
      ibuprofen, 6 were treated with 2 doses, and the remaining 2 were treated with 3
      doses. The survival rate at 1 month was 86.4% (19 of 22). Three (13.6%) infants
      died from the following causes: 1 who was born at 24 weeks' gestation with a
      birth weight of 380 g died as a result of extreme prematurity complications,
      necrotizing enterocolitis, and low birth weight; 1 died as a result of Candida
      sepsis; and the third died as a result of Klebsiella sepsis. Intraventricular
      hemorrhage was observed in 7 infants. The classification was changed from grade 2
      to grade 3 in 1 and from grade 0 to grade 1 or higher in 3 others. The rate of
      survival to discharge was 86.4% (19 of 22). No bronchopulmonary dysplasia was
      observed in the study group, and there was no case of tendency to bleed. There
      were no significant differences in the levels of serum creatinine before and
      after treatment with oral ibuprofen. CONCLUSIONS: Oral ibuprofen suspension may
      be an effective and safe alternative for PDA closure in premature infants with
      PDA. However, larger comparative studies are warranted.

PMID- 14595077
TI  - Cognitive and academic consequences of bronchopulmonary dysplasia and very low
      birth weight: 8-year-old outcomes.
AB  - OBJECTIVE: To examine the effects of bronchopulmonary dysplasia (BPD) and very
      low birth weight (VLBW) on the cognitive and academic achievement of a large
      sample of 8-year-old children. METHODS: Infants who were VLBW and had BPD (n =
      98) or did not have BPD (n = 75) and term infants (n = 99) were followed
      prospectively to age 8. Groups were compared on measures assessing 4 broad areas
      of functioning: intelligence, achievement, gross motor, and attentional skills.
      Measures included the Wechsler Intelligence Scale for Children III, the Woodcock
      Johnson Test of Achievement-Revised, the Bruininks-Oseretsky Test of Motor
      Proficiency, the Tactual Performance Test (spatial memory), and the Continuous
      Performance Test (attention). School outcomes were assessed by parent and teacher
      report, as well as from school records. Groups were comparable on socioeconomic
      status, sex, and race. The total sample of BPD, VLBW, and term children was
      compared on all outcome measures. In addition, neurologic risk was assessed in
      the present sample and included the following: intraventricular hemorrhage,
      echodense lesions, porencephaly, hydrocephalus, ventriculoperitoneal shunt,
      meningitis, and periventricular leukomalacia. Individual difference analyses were
      conducted for neurologically intact children in all 3 groups. Finally, treatment
      effects were examined by comparing BPD children who had received steroids as part
      of their treatment with BPD children who had not. RESULTS: The BPD group
      demonstrated deficits compared with VLBW and term children in intelligence;
      reading, mathematics, and gross motor skills; and special education services.
      VLBW children differed from term children in all of the above areas, except
      reading recognition, comprehension, and occupational therapy. Attentional
      differences were obtained between BPD and term children only. The BPD group (54%)
      was more likely to be enrolled in special education classes than VLBW (37%) or
      term children (25%). In addition, more BPD children (20%) achieved full-scale IQ
      scores <70, in the mental retardation range, compared with either VLBW (11%) or
      term (3%) children, with all VLBW children significantly more likely than term
      children to achieve IQs in the subaverage category. After controlling for birth
      weight and neurologic problems, BPD and/or duration on oxygen predicted lower
      performance IQ, perceptual organization, full-scale IQ, motor and attentional
      skills, and special education placement. The qualitative classification of BPD
      (present or absent) was a significant predictor for lower scores on measures of
      applied problems; motor skills; and incidence of speech-language, occupational,
      and physical therapies. Individual difference analyses were performed to
      ascertain whether differences between the risk groups were primarily attributable
      to neurologic complications. Even with the neurologically intact sample of BPD
      and VLBW children, differences between the term comparison group and both the BPD
      and VLBW groups were found for many outcome measures. When birth weight and
      neurologic complications were controlled, BPD and severity of BPD were associated
      with lower performance and full-scale IQ, poorer perceptual organization,
      attention, and motor skills, as well as lower school achievement and greater
      participation in special education, including occupational, physical, and speech
      language therapies. Treatment protocol may in part be responsible for differences
      observed in our BPD sample. Steroid and nonsteroid groups of BPD children
      differed significantly in performance IQ (72.8 vs 84.8) and full-scale IQ (77.0
      vs 85.2); perceptual organization (74.0 vs 85.2); Bruininks-Oseretsky Test of
      Motor Proficiency score (36.6 vs 44.7); and participation in special education
      (78% vs 48%), occupational therapy (71% vs 44%), and physical therapy (71% vs
      41%). In every instance, BPD children who received steroids fared more poorly
      than BPD children who did not receive steroids. CONCLUSIONS: BPD and duration on
      oxygen have long-term adverse effects on cognitive and academic achievement above
      and be beyond the effects of VLBW. The problems that have been identified at 8
      years of age highlight the need for continued monitoring of the learning,
      behavior, and development of BPD children to intervene with children who are at
      risk for school problems.

PMID- 14595078
TI  - Disparity between pediatricians' knowledge and practices regarding perinatal
      human immunodeficiency virus counseling and testing.
AB  - OBJECTIVES: This survey of members of the American Academy of Pediatrics (AAP)
      was initiated by the AAP Committee on Pediatric AIDS to assess the knowledge,
      attitudes, and behaviors of pediatricians regarding prenatal and neonatal
      screening as a means to reduce mother-to-child transmission of human
      immunodeficiency virus (HIV). METHODS: The survey consisted of a 4-page, self
      administered questionnaire, which was mailed to a random sample of 1647 active US
      members of the AAP. The original and 5 subsequent mailings to nonresponders were
      conducted from July to November 2001. RESULTS: Completed questionnaires were
      received from 982 pediatricians, for a response rate of 59.6%. Nearly all
      pediatricians (96.6%) agree on the importance of knowing the HIV status of
      pregnant women, and more than three-fourths (78.5%) do not think that HIV
      screening during pregnancy or postpartum should be limited to women with
      perceived risk for infection. Approximately 6 (58.5%) of 10 pediatricians
      indicate that they counsel or provide education on HIV screening to pregnant
      women or mothers of newborns whose HIV status is unknown; 41.5% do not.
      Pediatricians reported evaluating an average of 56 newborns each during the 3
      months before the survey. The HIV infection status of the mother was unknown for
      40.6% of these cases. During the same time period, pediatricians said that they
      discussed a newborn or maternal HIV screening test with only 10.4% of the mothers
      whose HIV infection status was unknown. Reasons given for not counseling mothers
      with unknown HIV infection status about maternal and/or newborn screening for HIV
      included low prevalence of HIV in the pediatrician's practice area (65.4%),
      assessment by the pediatrician that the parents did not fit the profile of those
      "at risk" for HIV infection (56.1%), fear of offending the parents (50.2%),
      parental lack of understanding regarding the importance of screening (50.1%), and
      lack of sufficient time for counseling (44.4%). CONCLUSIONS: Pediatricians
      exhibit a high degree of understanding of the importance of HIV screening as a
      means to reduce mother-to-child transmission of HIV, but this does not always
      translate into their clinical practices.

PMID- 14595079
TI  - Circumstances surrounding end of life in a pediatric intensive care unit.
AB  - OBJECTIVE: Approximately 60% of deaths in pediatric intensive care units follow
      limitation or withdrawal of life-sustaining treatment (LST). We aimed to describe
      the circumstances surrounding decision making and end-of-life care in this
      setting. METHODS: We conducted a prospective, descriptive study based on a survey
      with the intensivist after every consecutive death during an 8-month period in a
      single multidisciplinary pediatric intensive care unit. Summary statistics are
      presented as percentage, mean +/- standard deviation, or median and range; data
      are compared using the Mantel-Haenszel test and shown as survival curves.
      RESULTS: Of the 99 observed deaths, 27 involved failed cardiopulmonary
      resuscitation; of the remaining 72, 39 followed withdrawal/limitation (W/LT) of
      LST, 20 were do not resuscitate (DNR), and 13 were brain deaths (BDs). Families
      initiated discussions about forgoing LST in 24% (17 of 72) of cases. Consensus
      between caregivers and staff about forgoing LST as the best approach was reached
      after the first meeting with 51% (35 of 68) of families; 46% (31 of 68) required
      >or=2 meetings (4 not reported). In the DNR group, the median time to death after
      consensus was 24 hours and for W/LT was 3 hours. LST was later withdrawn in 11 of
      20 DNR cases. The family was present in 76% (45 of 59) of cases when LST was
      forgone. The dying patient was held by the family in 78% (35 of 45) of these
      occasions. CONCLUSIONS: More than 1 formal meeting was required to reach
      consensus with families about forgoing LST in almost half of the patients.
      Families often held their child at the time of death. The majority of children
      died quickly after the end-of-life decision was made.

PMID- 14595080
TI  - Increased diagnosis of Lemierre syndrome and other Fusobacterium necrophorum
      infections at a Children's Hospital.
AB  - OBJECTIVE: To assess the apparent increase in the diagnosis of Lemierre syndrome
      (LS) and other Fusobacterium necrophorum infections at a large children's
      hospital. Infections with F necrophorum ranged from peritonsillar abscess to
      potentially fatal LS. LS is an oropharyngeal infection characterized by septic
      thrombophlebitis of head and neck veins, complicated by dissemination of septic
      emboli to pulmonary and systemic sites. METHODS: Review of the medical and
      laboratory records was conducted of all patients who were seen at or admitted to
      the Children's Hospital of Wisconsin with the diagnosis of LS and/or isolation of
      F necrophorum from a clinical specimen between January 1995 and January 2002.
      RESULTS: During the 7-year period of the study, there was an increase in the
      isolation of F necrophorum from patients who were seen at Children's Hospital of
      Wisconsin, as well as the number of cases of LS. There was 1 isolation of F
      necrophorum from clinical specimens per year from 1996 to 1999, which increased
      to 10 isolates of the organism from January 2000 to January 2002. During the most
      recent period, January 2001-January 2002, 5 cases of LS were diagnosed, a
      distinctive entity not recognized previously at the institution. CONCLUSIONS: The
      cause for the recent increase in the number of serious infections caused by F
      necrophorum infection diagnosed at our institution is unclear but does not seem
      to be related to changes in microbiologic techniques or patient demography. We
      speculate that it could be attributable, in part, to alterations in antibiotic
      usage patterns in our region. Clinicians need to be aware of the increasing
      clinical importance of F necrophorum infections and the life-threatening nature
      of LS.

PMID- 14595081
TI  - Warfarin therapy in children who require long-term total parenteral nutrition.
AB  - OBJECTIVE: To determine whether warfarin can be safely administered to children
      who require long-term total parenteral nutrition (TPN), for the purpose of
      preventing central venous access device (CVAD)-related thrombosis. METHODS: A
      prospective cohort study was conducted of 8 children with short-gut syndrome or
      small intestinal anomalies. All patients received oral anticoagulant therapy
      (warfarin) managed by the hematology department at a tertiary pediatric center.
      Data collected included demographic details, nutritional intake, age, weight,
      history of deep vein thrombosis, number and functional duration of CVADs,
      warfarin requirements, and adverse event rates. RESULTS: A total of 15.2 warfarin
      years were studied prospectively. The target therapeutic range was achieved 51.1%
      of time. The mean dose of warfarin required to achieve the target therapeutic
      range (international normalized ratio) of 2.0 to 3.0 was 0.33 mg/kg/d. The mean
      duration between warfarin monitoring tests was 6.6 days. The median vitamin K
      intake per patient was 0.367 mg/kg/d (range: 0.018-2.85 mg/kg/d). Before
      commencing anticoagulant therapy, the mean CVAD duration was 160.9 days.
      Concomitant warfarin therapy was associated with a mean CVAD duration of 351.7
      days. There were no major bleeding events, and no clinical extension of
      thrombosis was observed. CONCLUSIONS: This is the first published study to report
      uniform warfarin prophylaxis for CVADs in children. Warfarin therapy can be
      administered safely in children who require long-term TPN. Warfarin prophylaxis
      seems to prolong CVAD survival.

PMID- 14595082
TI  - Indoor and outdoor environmental exposures, parental atopy, and physician
      diagnosed asthma in Taiwanese schoolchildren.
AB  - OBJECTIVE: Parental atopy and environmental exposures are recognized risk factors
      for childhood asthma. However, the relative contributions of specific risk
      factors and the overall contributions of indoor and outdoor exposures remain
      unexplored. This study was undertaken to identify risk factors, estimate the
      population attributable risk of each exposure, and compare the data for boys
      versus girls for physician-diagnosed asthma in Taiwanese schoolchildren. METHODS:
      During a February to June 2001 cross-sectional national survey, 35 036 6- to 15
      year-old schoolchildren were chosen from 22 elementary and 22 middle schools
      located within 1-km catchment areas of 22 air-monitoring stations in Taiwan. The
      main outcome measure was physician-diagnosed asthma, as reported by the parents.
      We investigated hereditary and indoor and outdoor environmental factors for
      childhood asthma by questionnaire. The adjusted prevalences of questionnaire
      determined outdoor indicators were also compared with air-monitoring data.
      RESULTS: Outdoor air pollutants were associated with parent-reported perceived
      ambient air pollution. Physician-diagnosed asthma was reported for 8.1% of the
      boys (1330 of 16 441) and 5.6% of the girls (894 of 16 056). The risk of
      physician-diagnosed asthma was significantly associated with parental atopy and
      perceived ambient air pollution in both sexes. The presence of visible
      cockroaches (odds ratio [OR]: 1.30; 95% confidence interval [CI]: 1.07-1.59),
      mold on walls at home (OR: 1.20; 95% CI: 1.01-1.41), and water damage (OR: 1.33;
      95% CI: 1.02-1.70) were also associated with asthma in girls; however, only
      visible mold on walls at home was related to asthma in boys. Mutually adjusted
      analytical models produced statistically significant associations between any
      indoor factor and asthma in girls (OR: 1.24; 95% CI: 1.00-1.56) but not in boys
      (OR: 1.04; 95% CI: 0.87-1.25). For all hereditary and environmental factors, the
      total population attributable risk was 44.31% in boys and 60.61% in girls.
      CONCLUSIONS: Parental atopy contributed more to childhood asthma than indoor or
      outdoor environmental factors. Girls may be more susceptible to indoor factors
      than boys.

PMID- 14595083
TI  - Childhood cancer among Alaska Natives.
AB  - OBJECTIVE: The primary purpose of this study was to examine the occurrence of
      cancer in Alaska Native (AN) children (under age 20). Although several studies
      have compared differences in cancer incidence between white and black children,
      few have examined cancer among Alaska Natives/American Indians. We know of no
      published article describing cancer incidence in AN children. We compared our
      findings with those of American Indian children of New Mexico and of Alaska white
      children. Data on mortality, survival, and prevalence are also included. Alaska
      Native is the term used collectively for the inhabitants whose ancestors occupied
      the area before European contact of what is now the state of Alaska. Alaska
      Natives include Eskimo, Indian, and Aleut groups. Although the 3 major groups
      differ in culture, language, and probably genetics, there are similarities in
      numerous social and economic indicators. The Northern Eskimo of Alaska (Inupiat)
      are related to Canadian and Greenland Inuit. Indians in Alaska include Athabaskan
      (in the interior of the state), who share commonalities with Canadian Athabaskan
      as well as with Navajo and Apache in the southwestern United States. Tlingit,
      Haida, and Tsimshian groups reside primarily in the southeast panhandle of the
      state. The panhandle Indian groups are similar to those of British Columbia.
      METHODS: Data on cancer incidence are from the Alaska Native Tumor Registry, 1969
      1996. We studied children under age 20 to make our results comparable to national
      data as presented in the National Cancer Institute's Surveillance, Epidemiology
      and End Results (SEER) Pediatric Monograph. Population data for AN are based on
      census data and Indian Health Service intercensal estimates. Data for US whites
      and New Mexico Indians are from the National Cancer Institute's SEER program.
      Calculations were made using SEERStat software. Data for Alaska whites are for
      the years 1996-2000. (The Alaska Cancer Registry has collected data for all
      Alaskans only since 1996). Odds ratios (ORs) of rates with 95% confidence
      intervals (CIs) were calculated. RESULTS: The rate among all AN children (both
      sexes) for all cancers combined is similar to that of US whites (OR: 1.0; 95% CI:
      0.8-1.1). Examination of childhood cancer rates by ethnicity, however, reveal
      that rates are significantly lower for Indian (OR: 0.6; 95% CI: 0.4-0.8) but not
      significantly different for Eskimo or Aleut children. For most International
      Classification of Childhood Cancers groups, incidence rates for AN children are
      also similar to those of US whites. However, AN children are at significantly
      higher risk for hepatic tumors (OR: 13.1; 95% CI: 7.9-20.5), particularly
      hepatocellular carcinoma (OR: 43.8; 95% CI:24.4-75.1) and retinoblastoma (OR:
      2.8; 95% CI: 1.3-5.3). By ethnic group, rates for hepatocellular carcinoma are
      significantly high only for Eskimo. Rates for all AN children are lower for
      neuroblastoma (OR: 0.1; 95% CI: 0.1-0.6) and lymphoma (OR: 0.5; 95% CI: 0.3-0.9),
      particularly Hodgkin's disease (OR: 0.2; 95% CI: 0.0-0.5). On the basis of 5
      years of data, rates for Alaska white children do not seem to differ from those
      of US white children. Because of our findings of differences between AN and US
      whites, we reviewed data of other relevant populations, specifically American
      Indian data from the New Mexico SEER registry. Using SEER data and SEER software,
      we calculated rates for New Mexican American Indians (NMAI) and compared them
      with US white rates. Rates for all cancers combined among NMAI are significantly
      lower than for US white (OR: 0.8). However, similar to AN children, the rate
      among NMAI for retinoblastoma is higher compared with US whites (OR: 2.5; 95%
      CI:1.4-4.5). Similar to AN, NMAI also seem to be at low risk for neuroblastoma
      (OR: 0.2; 95% CI: 0.1-0.7), lymphoma as a group (OR: 0.1; 95% CI: 0.0-0.3), and,
      specifically, Hodgkin's disease (OR: 0.1; 95% CI: 0.0-0.4). Rates among NMAI
      children are low for central nervous system tumors (OR: 0.5; 95% CI: 0.3-0.7).
      The average annual age-adjusted cancer mortality rate among AN children is lower
      but not significantly lower than that of US white children (28.6 vs 37.3 per
      million). CONCLUSIONS: Comparison of AN rates for all cancers combined are
      similar to those of US and Alaska white children but seem higher than those of
      NMAI. Differences between AN and US whites exist for select International
      Classification of Childhood Cancers groups. The most striking rate differences
      are found in hepatic tumors, largely because of elevated rates of hepatitis B
      associated hepatocellular carcinoma. All children in our study with
      hepatocellular carcinoma were hepatitis B antigen positive. A statewide hepatitis
      B virus immunization program was begun in late 1982. Although 16 children who
      were born before 1983 developed hepatocellular carcinoma, no children who were
      born in the 20 years since hepatitis B immunization was instituted among infants
      have received a diagnosis of hepatocellular carcinoma, a significant difference.
      Comparing AN and US white childhood cancer rates after removing hepatocellular
      carcinoma cases from both populations results in an OR of 0.8 (95% CI: 0.7-1.0).
      Thus, if no increase in other childhood cancers occurs in the coming generations,
      then rates for childhood cancer may soon be significantly lower than those in US
      white children. Rates are low for all lymphomas, largely because of very low
      rates of Hodgkin's disease. Rates are also low for neuroblastoma. It is
      reassuring that rates for AN children are not in excess and do not seem to be
      increasing. There is concern among the population regarding environmental
      exposure, including ionizing radiation. Our data do not show excess childhood
      leukemia or thyroid cancers, malignancies for which radiation is known to
      increase risk.

PMID- 14595084
TI  - A dose-response study of OROS methylphenidate in children with attention
      deficit/hyperactivity disorder.
AB  - OBJECTIVE: OROS methylphenidate HCL (MPH) is a recently developed long-acting
      stimulant medication used to treat attention-deficit/hyperactivity disorder
      (ADHD). This study was conducted to examine dosage effects on ADHD symptoms and
      stimulant side effects and to explore potential moderating effects of ADHD
      subtype. METHODS: Children with ADHD combined type (ADHD-CT) or predominantly
      inattentive type (ADHD-PI; n = 47), ages 5 to 16 years, underwent a placebo
      controlled, crossover trial using forced titration with weekly switches at 3
      dosage levels. Parent and teacher ratings of ADHD symptoms were used to evaluate
      efficacy. In addition, vital signs and standardized measures of stimulant side
      effects were obtained weekly. RESULTS: Parent ratings were more sensitive to
      treatment effects than teacher ratings. ADHD symptoms and Clinical Global
      Impressions Severity Index ratings at each dose condition differed significantly
      from placebo and baseline ratings, which did not differ from one another. For
      those with ADHD-CT, there was a clear linear dose-response relationship, with
      clinically significant reductions in ADHD Rating Scale-IV scores occurring in two
      thirds to three fourths of the subjects during either 36- or 54-mg dose
      conditions. Children with ADHD-PI, conversely, were more likely to respond
      optimally to lower doses and derived less benefit from higher doses, with 60%
      displaying significant improvement on the ADHD Rating Scale-IV at 36 mg or lower.
      Mild stimulant side effects were reported during placebo and at all dosage
      levels. With the exception of insomnia and decreased appetite, which were more
      common at higher doses, parent report of side effects was not related to dose. In
      addition, younger and smaller children were more likely to display sleep
      difficulties and decreased appetite at the higher dose levels Although pulse rate
      increased slightly with increasing dose, there were no dose effects on blood
      pressure. CONCLUSIONS: In children with ADHD-CT, the most common subtype of ADHD,
      increasing doses of stimulant medication were associated with increased
      improvement of inattention and hyperactivity symptoms. In children with ADHD-PI,
      symptom improvement occurred at lower doses and less benefit was derived from
      higher doses. In both ADHD subtypes, higher doses were associated with parent
      ratings of increased insomnia and decreased appetite.

PMID- 14595085
TI  - Low glycemic index breakfasts and reduced food intake in preadolescent children.
AB  - OBJECTIVE: Recent reports have suggested that a low glycemic index (GI) diet may
      have a role in the management of obesity through its ability to increase the
      satiety value of food and modulate appetite. To date, no long-term clinical
      trials have examined the effect of dietary GI on body weight regulation. The
      majority of evidence comes from single-day studies, most of which have been
      conducted in adults. The purpose of this study was to investigate the effect of 3
      test breakfasts-low-GI, low-GI with 10% added sucrose, and high-GI-on ad libitum
      lunch intake, appetite, and satiety and to compare these with baseline values
      when habitual breakfast was consumed. METHODS: A 3-way crossover study using
      block randomization of breakfast type was conducted in a school that already ran
      a breakfast club. A total of 37 children aged 9 to 12 years (15 boys and 22
      girls) completed the study. The proportion of nonoverweight to overweight/obese
      children was 70:30. Children were divided into 5 groups, and a rolling program
      was devised whereby, week by week, each group would randomly receive 1 of 3 test
      breakfasts for 3 consecutive days, with a minimum of 5 weeks between the test
      breakfasts. Participants acted as their own control. The 3 test breakfasts were
      devised to match the energy and nutritional content of an individual's habitual
      breakfast as far as possible. All test breakfasts were composed of fruit juice,
      cereal, and milk with/without bread and margarine; foods with an appropriate GI
      value were selected. After each test breakfast, children were instructed not to
      eat or drink anything until lunchtime, except water and a small serving of fruit
      supplying approximately 10 g of carbohydrate, which was provided. Breakfast
      palatability, satiation after breakfast, and satiety before lunch were measured
      using rating scales based on previously used tools. Lunch was a buffet-style
      meal, and children were allowed free access to a range of foods. Lunch was served
      in the school hall where the rest of the schoolchildren were eating. Food intake
      at lunch was unobtrusively observed and recorded. Leftovers and food swapping
      were recorded, and plate waste was estimated. Lunch intakes were analyzed using a
      multilevel regression model for repeated measures data. The likelihood ratio
      statistic was used to determine whether the type of breakfast eaten had a
      significant effect on lunch intake after allowing for sex and weight status.
      RESULTS: The type of breakfast eaten had a statistically significant effect on
      mean energy intake at lunchtime: lunch intake was lower after low-GI and low-GI
      with added sucrose breakfasts compared with lunch intake after high-GI and
      habitual breakfasts (which were high-GI). Overweight and sex did not have a
      significant effect on lunch intake. Pairwise comparisons among the 3 types of
      test breakfasts and between each test breakfast and habitual breakfast were made.
      Lunch intake after the high-GI breakfast was significantly higher than after the
      low-GI breakfast and low-GI breakfast with added sucrose. The details of the
      pairwise comparisons were as follows: high-GI versus low-GI = 145 +/- 54 kcal;
      high-GI versus low-GI plus sucrose = 119 +/- 53 kcal; low-GI plus sucrose versus
      low-GI = 27 +/- 54 kcal. Lunch intake after the low-GI breakfast and the low-GI
      breakfast with added sucrose was significantly lower than after the habitual
      breakfast. The details of the pairwise comparisons were as follows: low-GI versus
      habitual = -109 +/- 75 kcal; low-GI plus sucrose versus habitual = -83 +/- 75
      kcal; high-GI versus habitual = 36 +/- 75 kcal. There were no significant
      differences between the test breakfasts in immediate satiation. The high-GI
      breakfasts were rated to be more palatable than the low-GI breakfasts. At
      lunchtime, hunger ratings were greater after the high-GI breakfast compared with
      the other 2 test breakfasts on 2 of the 3 experimental days. Prelunch satiety
      scales were inversely related to subsequent food intake. CONCLUSIONS: These
      results suggest that low-GI foods eaten at breakfast have a significant impact on
      food intake at lunch. This is the first study to observe such an effect in a
      group of normal and overweight children and adds to the growing body of evidence
      that low-GI foods may have an important role in weight control and obesity
      management. The potentially confounding effect of differences in the
      macronutrient and dietary fiber content of the test breakfasts warrants
      additional study. In addition, the impact of GI on food intake and body weight
      regulation in the long term needs to be investigated.

PMID- 14595086
TI  - Increased prevalence of familial autoimmunity in probands with pervasive
      developmental disorders.
AB  - OBJECTIVES: Increased prevalence of familial autoimmune disease is a common
      finding among probands with various autoimmune disorders. Autistic disorder
      (autism) is a highly genetic disorder with known immune and immunogenetic
      abnormalities. Previous research has found an increased frequency of autoimmune
      disorders in families with autistic probands. We further investigated this
      association by determining the frequency of autoimmune disorders in families that
      have probands with pervasive developmental disorders (PDDs), including autism,
      compared with 2 control groups. METHODS: Three well-defined study groups,
      including 1) families that have a child with a PDD, 2) families that have a child
      with an autoimmune disorder, and 3) families with a healthy control child,
      constituted the sample. A questionnaire inquiring about which first- and second
      degree family members had received a diagnosis of having specific autoimmune
      disorders was completed by 101 families in each group. RESULTS: The frequency of
      autoimmune disorders was significantly higher in families of the PDD probands
      compared with families of both the autoimmune and healthy control probands.
      Autoimmunity was highest among the parents of PDD probands compared with parents
      of the healthy control subjects. Hypothyroidism/Hashimoto's thyroiditis and
      rheumatic fever were significantly more common in families with PDD probands than
      in the healthy control families. CONCLUSIONS: Autoimmunity was increased
      significantly in families with PDD compared with those of healthy and autoimmune
      control subjects. These preliminary findings warrant additional investigation
      into immune and autoimmune mechanisms in autism.

PMID- 14595088
TI  - Improvement of aggressive and antisocial behavior after resection of temporal
      lobe tumors.
AB  - Seizures associated with temporal lobe tumors may rarely manifest as episodic
      aggressive behavior. We describe 2 cases involving pediatric patients who
      presented with histories of unusually aggressive and antisocial behavior.
      Magnetic resonance imaging identified right mesial temporal lobe masses in both
      patients. After craniotomy for tumor removal, both patients were seizure-free and
      had marked reductions in their aggressive behavior. Tumors in the temporal lobe
      may be associated with behavioral problems, including aggression and rage
      attacks, which can be alleviated with surgical intervention. It is important to
      distinguish this subgroup of pediatric patients from those with alternative
      diagnoses such as attention-deficit/hyperactivity disorder or oppositional
      defiant disorder.

PMID- 14595087
TI  - Maternal fluoxetine treatment in the postpartum period: effects on platelet
      serotonin and plasma drug levels in breastfeeding mother-infant pairs.
AB  - OBJECTIVE: Postpartum major depression, a frequently (10%) occurring complication
      of childbirth, adversely affects the mother's functioning, the mother-infant
      relationship, and the child's subsequent development and propensity for later
      psychopathology. Although selective serotonin reuptake inhibitors (SSRIs) are
      effective in treating postpartum depression, concerns have been raised regarding
      their use in lactating women. Although plasma drug levels of infants who are
      exposed to SSRIs through breast milk are low compared with those typically seen
      in patients, infant levels in some reports do seem to be at or near the drugs'
      reported affinities (K(D)s) and IC(50)s for inhibition at the serotonin (5
      hydroxytryptamine [5-HT]) transporter. The impact of central serotonin 5-HT
      modulation by SSRIs during critical periods of brain development is unknown.
      These concerns have led our group to examine whether exposure through breast milk
      has a discernible effect on platelet 5-HT uptake. Taking advantage of the
      similarities between platelet and neuronal serotonin transporters, we previously
      used measurements of platelet 5-HT before and during maternal sertraline
      treatment to determine the degree of 5-HT transporter blockade in breastfed
      infants. We found that infants who were exposed to sertraline through their
      mothers' breast milk experienced little to no change in platelet 5-HT levels,
      suggestive of minimal effects on peripheral and central 5-HT transporter
      blockade. Compared with sertraline and most other SSRIs, fluoxetine and its
      active metabolite, norfluoxetine, have substantially longer plasma half-lives,
      and both compounds have been found in measurable quantities in plasma of nursing
      infants. Thus, to extend our previous work in this area, we measured platelet 5
      HT levels and plasma drug levels in breastfeeding mother-infant pairs before and
      during maternal treatment with fluoxetine. METHODS: Maternal and infant
      transporter blockade was assessed by measurement of platelet 5-HT in 11
      breastfeeding mother-infant pairs before and after 4 to 12 weeks of maternal
      fluoxetine (20-40 mg/d) treatment for postpartum depression. The study was
      approved by the Human Investigation Committee of Yale University School of
      Medicine, and each mother (mean age: 34.5 years; standard deviation [SD]: 5.3)
      gave written informed consent. Whole-blood 5-HT levels and plasma fluoxetine and
      norfluoxetine levels were determined by high-performance liquid chromatography.
      RESULTS: Five mothers were taking 20 mg of fluoxetine daily, 4 were taking 30 mg
      daily, and 2 were taking 40 mg daily. Mean infant age at the start of the study
      was 16.8 (SD: 8.8) weeks. All infants except 1 were <6 months of age and 4 were
      <3 months of age when their mothers began treatment. Six infants were breastfed
      exclusively; the remaining were breastfed between 3 and 8 times daily and were
      given supplemental feedings. Mean maternal postexposure 5-HT levels of 22.9 ng/mL
      (SD: 12.5) were markedly lower than mean preexposure (baseline) levels of 156.6
      ng/mL (SD: 71.4; paired t = 6.9, df = 10). In contrast, the mean infant pre- and
      postexposure 5-HT concentrations of 217.1 (SD: 66.5) and 229.9 (SD: 83.5) ng/mL,
      respectively, were similar (paired t = -0.24, df = 10). However, the 1 infant
      with measurable plasma fluoxetine had a substantial decline in 5-HT to 40% of
      baseline. In samples obtained from the same infant 4 months later, plasma drug
      levels were undetectable (<1 ng/mL) and the platelet serotonin levels were no
      longer reduced (12% increase from baseline). CONCLUSIONS: The marked declines (to
      9%-28% of baseline) in platelet 5-HT concentrations seen in mothers who were
      treated with the SSRI fluoxetine were similar to those observed in our study of
      sertraline in breastfeeding and other previous studies. In contrast, all but 1
      infant experienced little or no decline in whole-blood (platelet) 5-HT
      concentrations after exposure to fluoxetine through breast milk. The substantial
      drop in platelet 5-HT seen in 1 infant and the coupling of this drop with
      measurable plasma fluoxetine leves drop with measurable plasma fluoxetine level
      raises some concern. Possible reasons for the infant's measurable plasma
      fluoxetine level include his mother's high plasma drug level and his being
      breastfed exclusively. However, the observations may be coincidental, and the
      infant experienced no discernible adverse effects. These data suggest that most
      infants may continue to breastfeed without experiencing meaningful changes in
      platelet 5-HT transport while their mothers are treated with 20 to 40 mg of
      fluoxetine daily. Given the limited data regarding occurrence and extent of SSRI
      exposure and the uncertainties concerning the possible effects of exposure, it is
      premature to propose treatment guidelines. Our own advice to women who are
      thinking of combining breastfeeding and SSRI treatment will weigh a range of
      factors, including severity of postpartum depression, any demonstrated
      preferential response to a specific SSRI, and the mother's commitment to
      breastfeeding. Additional research is needed to establish more definitively the
      frequency of physiologically meaningful infant SSRI exposure during breastfeeding
      and to determine the behavioral consequences of such exposure.

PMID- 14595089
TI  - Intrathoracic disease from nontuberculous mycobacteria in children: two cases and
      a review of the literature.
AB  - Pulmonary disease caused by nontuberculous mycobacteria (NTM) is a relatively
      rare occurrence in immunocompetent children. Two cases of endobronchial NTM
      infection in immunocompetent children are described. In addition, 41 other
      children with NTM pulmonary disease reported in the English literature between
      1930 and 2003 are reviewed. Clinical manifestations are either purely respiratory
      or respiratory with more widespread systemic symptoms. Compared with children
      with only respiratory complaints, children with constitutional symptoms from NTM
      pulmonary disease 1) had symptoms for a shorter period before presentation (10 vs
      28 days), 2) had more radiographic evidence of pulmonary disease, and 3) were
      treated longer with antimycobacterial agents (11.5 months vs 6 months). The most
      common causative organism was Mycobacterium avium complex. Pediatricians should
      be increasingly aware of NTM in the differential diagnosis of persistent
      pulmonary disease in previously healthy children.

PMID- 14595090
TI  - How meaningful are Bayesian support values?
AB  - In this study, we used an empirical example based on 100 mitochondrial genomes
      from higher teleost fishes to compare the accuracy of parsimony-based jackknife
      values with Bayesian support values. Phylogenetic analyses of 366 partitions,
      using differential taxon and character sampling from the entire data matrix of
      100 taxa and 7,990 characters, were performed for both phylogenetic methods. The
      tree topology and branch-support values from each partition were compared with
      the tree inferred from all taxa and characters. Using this approach, we
      quantified the accuracy of the branch-support values assigned by the jackknife
      and Bayesian methods, with respect to each of 15 basal clades. In comparing the
      jackknife and Bayesian methods, we found that (1) both measures of support differ
      significantly from an ideal support index; (2) the jackknife underestimated
      support values; (3) the Bayesian method consistently overestimated support; (4)
      the magnitude by which Bayesian values overestimate support exceeds the magnitude
      by which the jackknife underestimates support; and (5) both methods performed
      poorly when taxon sampling was increased and character sampling was not
      increases. These results indicate that (1) the higher Bayesian support values are
      inappropriate (in magnitude), and (2) Bayesian support values should not be
      interpreted as probabilities that clades are correctly resolved. We advocate the
      continued use of the relatively conservative bootstrap and jackknife approaches
      to estimating branch support rather than the more extreme overestimates provided
      by the Markov Chain Monte Carlo-based Bayesian methods.

PMID- 14595091
TI  - Evolutionary and structural analyses of GDAP1, involved in Charcot-Marie-Tooth
      disease, characterize a novel class of glutathione transferase-related genes.
AB  - Mutations in the Ganglioside-induced differentiation-associated protein-1 (GDAP1)
      gene cause autosomal recessive Charcot-Marie-Tooth disease type 4A. The protein
      encoded by GDAP1 shows clear similarity to glutathione transferases (also known
      as glutathione S-transferases or GSTs). The human genome contains a paralog of
      GDAP1 called GDAP1L1. Using comparative genomics, we show that orthologs of GDAP1
      and GDAP1L1 are found in mammals, birds, amphibians, and fishes. Likely orthologs
      of those genes in invertebrates and a low but consistent similarity with some
      plant and eubacterial genes have also been found. We demonstrate that GDAP1 and
      GDAP1L1 do not belong to any of the known classes of GST genes. In addition to
      having distinctive sequences, GDAP1 and its relatives are also characterized by
      an extended region in GST domain II, absent in most other GSTs, and by a C
      terminal end predicted to contain transmembrane domains. Mutations affecting any
      of those characteristic domains are known to cause Charcot-Marie-Tooth disease.
      These features define the GDAP1 class of GST-like proteins.

PMID- 14595092
TI  - Ancient DNA enables timing of the pleistocene origin and holocene expansion of
      two adelie penguin lineages in antarctica.
AB  - The timing of divergent events in history is one of the central goals of
      contemporary evolutionary biology. Such studies are however dependent on accurate
      evolutionary rates. Recent developments in ancient DNA analysis enable the
      estimation of more accurate evolutionary rates and therefore more accurate timing
      of divergence events. Consequently, this leads to a better understanding of
      changes in populations through time. We use an evolutionary rate calculated from
      ancient DNA of Adelie penguins (Pygoscelis adeliae) to time divergent events in
      their history. We report the presence of two distinct and highly variable
      mitochondrial DNA lineages and track changes in these lineages through space and
      time. When the ancient DNA and the phylogenetic rates are used to estimate the
      time of origin of the lineages, two very different estimates resulted. In
      addition, these same rates provide very different estimates of the time of
      expansion of these lineages. We suggest that the rate calculated from ancient DNA
      is more consistent with the glacial history of Antarctica and requires fewer
      assumptions than does a narrative based on the phylogenetic rate. Finally, we
      suggest that our study indicates an important new role for ancient DNA studies in
      the timing of divergent events in history.

PMID- 14595093
TI  - The mitochondrial genome of Phoronis architecta--comparisons demonstrate that
      phoronids are lophotrochozoan protostomes.
AB  - The proper reconstruction of the relationships among the animal phyla is central
      to interpreting patterns of animal evolution from the genomic level to the
      morphological level. This is true not only of the more speciose phyla but also of
      smaller groups. We report here the nearly complete DNA sequence of the
      mitochondrial genome of the phoronid Phoronis architecta, which has a gene
      arrangement remarkably similar to that of a protostome animal, the chiton
      Katharina tunicata. Evolutionary analysis of both gene arrangements and inferred
      amino acid sequences of these taxa, along with those of three brachiopods and
      other diverse animals, strongly supports the hypothesis that lophophorates are
      part of the large group that includes mollusks and annelids-i.e., the
      Lophotrochozoa-and solidly refutes the alternative of their being deuterostomes.

PMID- 14595094
TI  - Mammalian housekeeping genes evolve more slowly than tissue-specific genes.
AB  - Do housekeeping genes, which are turned on most of the time in almost every
      tissue, evolve more slowly than genes that are turned on only at specific
      developmental times or tissues? Recent large-scale gene expression studies enable
      us to have a better definition of housekeeping genes and to address the above
      question in detail. In this study, we examined 1581 human-mouse orthologous gene
      pairs for their patterns of sequence evolution, contrasting housekeeping genes
      with tissue-specific genes. Our results show that, in comparison to tissue
      specific genes, housekeeping genes on average evolve more slowly and are under
      stronger selective constraints as reflected by significantly smaller values of
      Ka/Ks. Besides stronger purifying selection, we explored several other factors
      that can possibly slow down nonsynonymous rates in housekeeping genes. Although
      mutational bias might slightly slow the nonsynonymous rates in housekeeping
      genes, it is unlikely to be the major cause of the rate difference between the
      two types of genes. The codon usage pattern of housekeeping genes does not seem
      to differ from that of tissue-specific genes. Moreover, contrary to the old
      textbook concept, we found that approximately 74% of the housekeeping genes in
      our study belong to multigene families, not significantly different from that of
      the tissue-specific genes ( approximately 70%). Therefore, the stronger selective
      constraints on housekeeping genes are not due to a lower degree of genetic
      redundancy.

PMID- 14595096
TI  - Low levels of nucleotide diversity in mammalian Y chromosomes.
AB  - Sex chromosomes provide a useful context for the study of the relative importance
      of evolutionary forces affecting genetic diversity. The human Y chromosome shows
      levels of nucleotide diversity 20% that of autosomes, which is significantly less
      than expected when differences in effective population size and sex-specific
      mutation rates are taken into account. To study the generality of low levels of Y
      chromosome variability in mammalian genomes, we investigated nucleotide diversity
      in intron sequences of X (1.1-3.0 kb) and Y (0.7-3.5 kb) chromosome genes of five
      mammals: lynx, wolf, reindeer, cattle, and field vole. For all species,
      nucleotide diversity was found to be lower on Y than on X, with no segregating
      site observed in Y-linked sequences of lynx, reindeer, and cattle. For X
      chromosome sequences, nucleotide diversity was in the range of 1.6 x 10(-4)
      (lynx) to 8.0 x 10(-4) (field vole). When differences in effective population
      size and the extent of the male mutation bias were taken into account, all five
      species showed evidence of reduced levels of Y chromosome variability. Reduced
      levels of Y chromosome variability have also been observed in Drosophila and in
      plants, as well as in the female-specific W chromosome of birds. Among the
      different factors proposed to explain low levels of genetic variability in the
      sex-limited chromosome (Y/W), we note that selection is the only factor that is
      broadly applicable irrespective of mode of reproduction and whether there is male
      or female heterogamety.

PMID- 14595095
TI  - High-resolution SNPs and microsatellite haplotypes point to a single, recent
      entry of Native American Y chromosomes into the Americas.
AB  - A total of 63 binary polymorphisms and 10 short tandem repeats (STRs) were
      genotyped on a sample of 2,344 Y chromosomes from 18 Native American, 28 Asian,
      and 5 European populations to investigate the origin(s) of Native American
      paternal lineages. All three of Greenberg's major linguistic divisions (including
      342 Amerind speakers, 186 Na-Dene speakers, and 60 Aleut-Eskimo speakers) were
      represented in our sample of 588 Native Americans. Single-nucleotide polymorphism
      (SNP) analysis indicated that three major haplogroups, denoted as C, Q, and R,
      accounted for nearly 96% of Native American Y chromosomes. Haplogroups C and Q
      were deemed to represent early Native American founding Y chromosome lineages;
      however, most haplogroup R lineages present in Native Americans most likely came
      from recent admixture with Europeans. Although different phylogeographic and STR
      diversity patterns for the two major founding haplogroups previously led to the
      inference that they were carried from Asia to the Americas separately, the
      hypothesis of a single migration of a polymorphic founding population better fits
      our expanded database. Phylogenetic analyses of STR variation within haplogroups
      C and Q traced both lineages to a probable ancestral homeland in the vicinity of
      the Altai Mountains in Southwest Siberia. Divergence dates between the Altai plus
      North Asians versus the Native American population system ranged from 10,100 to
      17,200 years for all lineages, precluding a very early entry into the Americas.

PMID- 14595097
TI  - Birth and evolutionary history of a human minisatellite.
AB  - One of the most exciting challenges in human biology is the understanding of how
      our genome was constructed during evolution. Here we explore the evolutionary
      history of the low polymorphic human minisatellite MsH42 and its flanking
      sequences. We show that the evolutionary birth of MsH42 took place within an
      intron, early in primate lineage evolution, more than 40 MYA. Then, single base
      pair changes and duplications/deletions of repeat blocks by mispairing were
      probably the main forces governing the generation of this minisatellite and its
      polymorphism throughout primate evolution. Moreover, we detected several
      phylogenetic footprints at both sides of MsH42. We believe that our findings will
      contribute to the understanding of low-variability minisatellite evolution.

PMID- 14595098
TI  - Comparative molecular population genetics of the Xdh locus in the cactophilic
      sibling species Drosophila buzzatii and D. koepferae.
AB  - The Xdh (rosy) gene is one of the best studied in the Drosophila genus from an
      evolutionary viewpoint. Here we analyze nucleotide variation in a 1875-bp
      fragment of the second exon of Xdh in Argentinian populations of the cactophilic
      D. buzzatii and its sibling D. koepferae. The major electrophoretic alleles of D.
      buzzatii not only lack diagnostic amino acids in the region studied but also
      differ on average from each other by four to 13 amino acid changes. Our data also
      suggest that D. buzzatii populations belonging to different phytogeographic
      regions are not genetically differentiated, whereas D. koepferae exhibits a
      significant pattern of population structure. The Xdh region studied is twice as
      polymorphic in D. buzzatii as in D. koepferae. Differences in historical
      population size or in recombinational environment between species could account
      for the differences in the level of nucleotide variation. In both species, the
      Xdh region exhibits a great number of singletons, which significantly departs
      from the frequency spectrum expected under neutrality for nonsynonymous sites and
      also for synonymous sites in D. buzzatii. These excesses of singletons could be
      the signature of a recent population expansion in D. buzzatii, whereas they may
      be simply explained as the result of negative selection in D. koepferae.

PMID- 14595099
TI  - The evolution of homing endonuclease genes and group I introns in nuclear rDNA.
AB  - Group I introns are autonomous genetic elements that can catalyze their own
      excision from pre-RNA. Understanding how group I introns move in nuclear
      ribosomal (r)DNA remains an important question in evolutionary biology. Two
      models are invoked to explain group I intron movement. The first is termed homing
      and results from the action of an intron-encoded homing endonuclease that
      recognizes and cleaves an intronless allele at or near the intron insertion site.
      Alternatively, introns can be inserted into RNA through reverse splicing. Here,
      we present the sequences of two large group I introns from fungal nuclear rDNA,
      which both encode putative full-length homing endonuclease genes (HEGs). Five
      remnant HEGs in different fungal species are also reported. This brings the total
      number of known nuclear HEGs from 15 to 22. We determined the phylogeny of all
      known nuclear HEGs and their associated introns. We found evidence for intron
      independent HEG invasion into both homologous and heterologous introns in often
      distantly related lineages, as well as the "switching" of HEGs between different
      intron peripheral loops and between sense and antisense strands of intron DNA.
      These results suggest that nuclear HEGs are frequently mobilized. HEG invasion
      appears, however, to be limited to existing introns in the same or neighboring
      sites. To study the intron-HEG relationship in more detail, the S943 group I
      intron in fungal small-subunit rDNA was used as a model system. The S943 HEG is
      shown to be widely distributed as functional, inactivated, or remnant ORFs in
      S943 introns.

PMID- 14595100
TI  - An analysis of determinants of amino acids substitution rates in bacterial
      proteins.
AB  - The variation of amino acid substitution rates in proteins depends on several
      variables. Among these, the protein's expression level, functional category,
      essentiality, or metabolic costs of its amino acid residues may play an important
      role. However, the relative importance of each variable has not yet been
      evaluated in comparative analyses. To this aim, we made regression analyses
      combining data available on these variables and on evolutionary rates, in two
      well-documented model bacteria, Escherichia coli and Bacillus subtilis. In both
      bacteria, the level of expression of the protein in the cell was by far the most
      important driving force constraining the amino acids substitution rate.
      Subsequent inclusion in the analysis of the other variables added little further
      information. Furthermore, when the rates of synonymous substitutions were
      included in the analysis of the E. coli data, only the variable expression levels
      remained statistically significant. The rate of nonsynonymous substitution was
      shown to correlate with expression levels independently of the rate of synonymous
      substitution. These results suggest an important direct influence of expression
      levels, or at least codon usage bias for translation optimization, on the rates
      of nonsynonymous substitutions in bacteria. They also indicate that when a
      control for this variable is included, essentiality plays no significant role in
      the rate of protein evolution in bacteria, as is the case in eukaryotes.

PMID- 14595101
TI  - Mutational bias affects protein evolution in flowering plants.
AB  - Amino acid sequences from several thousand homologous gene pairs were compared
      for two plant genomes, Oryza sativa and Arabidopsis thaliana. The Arabidopsis
      genes all have similar G+C (guanine plus cytosine) contents, whereas their
      homologs in rice span a wide range of G+C levels. The results show that those
      rice genes that display increased divergence in their nucleotide composition
      (specifically, increased G+C content) showed a corresponding, predictable change
      in the amino acid compositions of the encoded proteins relative to their
      Arabidopsis homologs. This trend was not seen in a "control" set of rice genes
      that had nucleotide contents closer to their Arabidopsis homologs. In addition to
      showing an overall difference in the amino acid composition of the homologous
      proteins, we were also able to investigate the biased patterns of amino acid
      substitution since the divergence of these two species. We found that the amino
      acid exchange matrix was highly asymmetric when comparing the High G+C rice genes
      with their Arabidopsis homologs. Finally, we investigated the possible causes of
      this biased pattern of sequence evolution. Our results indicate that the biased
      pattern of protein evolution is the consequence, rather than the cause, of the
      corresponding changes in nucleotide content. In fact, there is an even more
      marked asymmetry in the patterns of substitution at synonymous nucleotide sites.
      Surprisingly, there is a very strong negative correlation between the level of
      nucleotide bias and the length of the coding sequences within the rice genome.
      This difference in gene length may provide important clues about the underlying
      mechanisms.

PMID- 14595102
TI  - Origin and phylogeny of chloroplasts revealed by a simple correlation analysis of
      complete genomes.
AB  - The complete sequenced genomes of chloroplast have provided much information on
      the origin and evolution of this organelle. In this paper we attempt to use these
      sequences to test a novel approach for phylogenetic analysis of complete genomes
      based on correlation analysis of compositional vectors. All protein sequences
      from 21 complete chloroplast genomes are analyzed in comparison with selected
      archaea, eubacteria, and eukaryotes. The distance-based analysis shows that the
      chloroplast genomes are most closely related to cyanobacteria, consistent with
      the endosymbiotic origin of chloroplasts. The chloroplast genomes are separated
      to two major clades corresponding to chlorophytes (green plants) s.l. and
      rhodophytes (red algae) s.l. The interrelationships among the chloroplasts are
      largely in agreement with the current understanding on chloroplast evolution. For
      instance, the analysis places the chloroplasts of two chromophytes (Guillardia
      and Odontella) within the rhodophyte lineage, supporting secondary endosymbiosis
      as the source of these chloroplasts. The relationships among the green algae and
      land plants in our tree also agree with results from traditional phylogenetic
      analyses. Thus, this study establishes the value of our simple correlation
      analysis in elucidating the evolutionary relationships among genomes. It is hoped
      that this approach will provide insights on comparative genome analysis.

PMID- 14595103
TI  - Highly heterogeneous rates of evolution in the SKP1 gene family in plants and
      animals: functional and evolutionary implications.
AB  - Skp1 (S-phase kinase-associated protein 1) is a core component of SCF ubiquitin
      ligases and mediates protein degradation, thereby regulating eukaryotic
      fundamental processes such as cell cycle progression, transcriptional regulation,
      and signal transduction. Among the four components of the SCF complexes, Rbx1 and
      Cullin form a core catalytic complex, an F-box protein acts as a receptor for
      target proteins, and Skp1 is an adaptor between one of the variable F-box
      proteins and Cullin. Whereas protists, fungi, and some vertebrates have a single
      SKP1 gene, many animal and plant species possess multiple SKP1 homologs. It has
      been shown that the same Skp1 homolog can interact with two or more F-box
      proteins, and different Skp1 homologs from the same species sometimes can
      interact with the same F-box protein. In this paper, we demonstrate that multiple
      Skp1 homologs from the same species have evolved at highly heterogeneous rates.
      Parametric bootstrap analyses suggested that the differences in evolutionary rate
      are so large that true phylogenies were not recoverable from the full data set.
      Only when the original data set were partitioned into sets of genes with slow,
      medium, and rapid rates of evolution and analyzed separately, better-resolved
      relationships were observed. The slowly evolving Skp1 homologs, which are
      relatively highly conserved in sequence and expressed widely and/or at high
      levels, usually have very low d(N)/d(S) values, suggesting that they have evolved
      under functional constraint and serve the most fundamental function(s). On the
      other hand, the rapidly evolving members are structurally more diverse and
      usually have limited expression patterns and higher d(N)/d(S) values, suggesting
      that they may have evolved under relaxed or altered constraint, or even under
      positive selection. Some rapidly evolving members may have lost their original
      function(s) and/or acquired new function(s) or become pseudogenes, as suggested
      by their expression patterns, d(N)/d(S) values, and amino acid changes at key
      positions. In addition, our analyses revealed several monophyletic groups within
      the SKP1 gene family, one for each of protists, fungi, animals, and plants, as
      well as nematodes, arthropods, and angiosperms, suggesting that the extant SKP1
      genes within each of these eukaryote groups shared only one common ancestor.

PMID- 14595104
TI  - Tor pathway regulates Rrn3p-dependent recruitment of yeast RNA polymerase I to
      the promoter but does not participate in alteration of the number of active
      genes.
AB  - Yeast cells entering into stationary phase decrease rRNA synthesis rate by
      decreasing both the number of active genes and the transcription rate of
      individual active genes. Using chromatin immunoprecipitation assays, we found
      that the association of RNA polymerase I with the promoter and the coding region
      of rDNA is decreased in stationary phase, but association of transcription factor
      UAF with the promoter is unchanged. Similar changes were also observed when
      growing cells were treated with rapamycin, which is known to inhibit the Tor
      signaling system. Rapamycin treatment also caused a decrease in the amount of
      Rrn3p-polymerase I complex, similar to stationary phase. Because recruitment of
      Pol I to the rDNA promoter is Rrn3p-dependent as shown in this work, these data
      suggest that the decrease in the transcription rate of individual active genes in
      stationary phase is achieved by the Tor signaling system acting at the Rrn3p
      dependent polymerase recruitment step. Miller chromatin spreads of cells treated
      with rapamycin and cells in post-log phase confirm this conclusion and
      demonstrate that the Tor system does not participate in alteration of the number
      of active genes observed for cells entering into stationary phase.

PMID- 14595105
TI  - Uniform cAMP stimulation of Dictyostelium cells induces localized patches of
      signal transduction and pseudopodia.
AB  - The chemoattractant cAMP induces the translocation of cytosolic PHCrac-GFP to the
      plasma membrane. PHCrac-GFP is a green fluorescent protein fused to a PH domain
      that presumably binds to phosphatydylinositol polyphosphates in the membrane. We
      determined the relative concentration of PHCrac-GFP in the cytosol and at
      different places along the cell boundary. In cells stimulated homogeneously with
      1microM cAMP we observed two distinct phases of PHCrac-GFP translocation. The
      first translocation is transient and occurs to nearly the entire boundary of the
      cell; the response is maximal at 6-8 s after stimulation and disappears after
      approximately 20 s. A second translocation of PHCrac-GFP starts after
      approximately 30 s and persists as long as cAMP remains present. Translocation
      during this second response occurs to small patches with radius of approximately
      4-5 microm, each covering approximately 10% of the cell surface. Membrane patches
      of PHCrac-GFP are both temporally and spatially closely associated with
      pseudopodia, which are extended at approximately 10 s from the area with a PHCrac
      GFP patch. These signaling patches in pseudopodia of homogeneously stimulated
      cells resemble the single patch of PHCrac-GFP at the leading edge of a cell in a
      gradient of cAMP, suggesting that PHCrac-GFP is a spatial cue for pseudopod
      formation also in uniform cAMP.

PMID- 14595106
TI  - Epithelial cell polarity alters Rho-GTPase responses to Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa is an opportunistic human pathogen that preferentially
      infects damaged epithelial tissues. Previous studies have failed to distinguish
      whether the increased susceptibility of injured epithelium results from the loss
      of cell polarity or increased access to the basolateral surface. We have used
      confluent monolayers of Madin-Darby canine kidney (MDCK) cells cultured on porous
      filter supports for 1-3 d as a model system to investigate whether the
      differentiation state of a polarized model epithelium affected the response of
      epithelial cells to this pathogen. Confluent incompletely polarized MDCK cell
      monolayers (day 1) efficiently internalized apically applied P. aeruginosa via a
      pathway that required actin polymerization and activation of Rho-family GTPases
      and was accompanied by an increase in the amount of activated RhoA. In contrast,
      P. aeruginosa entry into highly polarized MDCK monolayers (day 3) was 10- to 100
      fold less efficient and was insensitive to inhibitors of actin polymerization or
      of Rho-family GTPase activation. There was no activation of RhoA; instead, Cdc42
      GTP levels increased significantly. Basolateral infection of highly polarized
      MDCK monolayers was less efficient and insensitive to Clostridium difficile Toxin
      B, whereas basolateral infection of incompletely polarized MDCK monolayers was
      more efficient and required activation of Rho-family GTPases. Together, our
      findings suggest that as epithelial barrier differentiates and becomes highly
      polarized, it becomes resistant to P. aeruginosa infection. Nevertheless,
      polarized epithelial cells still sense the presence of apically infecting P.
      aeruginosa, but they may do so through a different group of surface proteins
      and/or downstream signaling pathways than do incompletely polarized cells.

PMID- 14595107
TI  - Unique and redundant roles for HOG MAPK pathway components as revealed by whole
      genome expression analysis.
AB  - The Saccharomyces cerevisiae high osmolarity glycerol (HOG) mitogen-activated
      protein kinase pathway is required for osmoadaptation and contains two branches
      that activate a mitogen-activated protein kinase (Hog1) via a mitogen-activated
      protein kinase kinase (Pbs2). We have characterized the roles of common pathway
      components (Hog1 and Pbs2) and components in the two upstream branches (Ste11,
      Sho1, and Ssk1) in response to elevated osmolarity by using whole-genome
      expression profiling. Several new features of the HOG pathway were revealed.
      First, Hog1 functions during gene induction and repression, cross talk
      inhibition, and in governing the regulatory period. Second, the phenotypes of
      pbs2 and hog1 mutants are identical, indicating that the sole role of Pbs2 is to
      activate Hog1. Third, the existence of genes whose induction is dependent on Hog1
      and Pbs2 but not on Ste11 and Ssk1 suggests that there are additional inputs into
      Pbs2 under our inducing conditions. Fourth, the two upstream pathway branches are
      not redundant: the Sln1-Ssk1 branch has a much more prominent role than the Sho1
      Ste11 branch for activation of Pbs2 by modest osmolarity. Finally, the general
      stress response pathway and both branches of the HOG pathway all function at high
      osmolarity. These studies demonstrate that cells respond to increased osmolarity
      by using different signal transduction machinery under different conditions.

PMID- 14595108
TI  - GLUT4 is retained by an intracellular cycle of vesicle formation and fusion with
      endosomes.
AB  - The intracellularly stored GLUT4 glucose transporter is rapidly translocated to
      the cell surface upon insulin stimulation. Regulation of GLUT4 distribution is
      key for the maintenance of whole body glucose homeostasis. We find that GLUT4 is
      excluded from the plasma membrane of adipocytes by a dynamic retention/retrieval
      mechanism. Our kinetic studies indicate that GLUT4-containing vesicles
      continually bud and fuse with endosomes in the absence of insulin and that these
      GLUT4 vesicles are 5 times as likely to fuse with an endosome as with the plasma
      membrane. We hypothesize that this intracellular cycle of vesicle budding and
      fusion is an element of the active mechanism by which GLUT4 is retained. The
      GLUT4 trafficking pathway does not extensively overlap with that of furin,
      indicating that the trans-Golgi network, a compartment in which furin
      accumulates, is not a significant storage reservoir of GLUT4. An intact
      microtubule cytoskeleton is required for insulin-stimulated recruitment to the
      cell surface, although it is not required for the basal budding/fusion cycle.
      Nocodazole disruption of the microtubule cytoskeleton reduces the insulin
      stimulated exocytosis of GLUT4, accounting for the reduced insulin-stimulated
      translocation of GLUT4 to the cell surface.

PMID- 14595109
TI  - Mek1 kinase activity functions downstream of RED1 in the regulation of meiotic
      double strand break repair in budding yeast.
AB  - Three meiosis-specific chromosomal components in budding yeast, Mek1, Red1, and
      Hop1, are required for recombination, proper segregation of homologs, and the
      meiotic recombination checkpoint. Mek1 is a protein kinase. Mutations that
      increase the size of the ATP binding pocket of Mek1 (mek1-as1) sensitize the
      kinase to specific small molecule inhibitors. Experiments using mek1-as1
      demonstrate that the requirement for Mek1 kinase activity coincides with the
      formation of double strand breaks (DSBs) and that this activity is necessary
      after DSB formation to prevent repair by DMC1-independent pathways. Contrary to
      previous reports, Red1 is not a substrate for Mek1. Instead, RED1 is required for
      wild-type levels of Mek1 kinase activity. In addition, activation of Mek1
      requires HOP1, the formation of Red1/Hop1 complexes and a functional Mek1 FHA
      domain. The requirement for RED1 to produce active kinase can be bypassed by a
      mek1 mutation that creates a constitutively active Mek1 kinase. We propose that
      Red1 is phosphorylated by a kinase other than MEK1 and that phosphothreonines on
      Red1 then interact with the Mek1 FHA domain to recruit the kinase to sites of
      DSBs where Mek1 is activated to prevent DMC1-independent DSB repair.

PMID- 14595110
TI  - Endocytosed cation-independent mannose 6-phosphate receptor traffics via the
      endocytic recycling compartment en route to the trans-Golgi network and a
      subpopulation of late endosomes.
AB  - Although the distribution of the cation-independent mannose 6-phosphate receptor
      (CI-MPR) has been well studied, its intracellular itinerary and trafficking
      kinetics remain uncertain. In this report, we describe the endocytic trafficking
      and steady-state localization of a chimeric form of the CI-MPR containing the
      ecto-domain of the bovine CI-MPR and the murine transmembrane and cytoplasmic
      domains expressed in a CHO cell line. Detailed confocal microscopy analysis
      revealed that internalized chimeric CI-MPR overlaps almost completely with the
      endogenous CI-MPR but only partially with individual markers for the trans-Golgi
      network or other endosomal compartments. After endocytosis, the chimeric receptor
      first enters sorting endosomes, and it then accumulates in the endocytic
      recycling compartment. A large fraction of the receptors return to the plasma
      membrane, but some are delivered to the trans-Golgi network and/or late
      endosomes. Over the course of an hour, the endocytosed receptors achieve their
      steady-state distribution. Importantly, the receptor does not start to colocalize
      with late endosomal markers until after it has passed through the endocytic
      recycling compartment. In CHO cells, only a small fraction of the receptor is
      ever detected in endosomes bearing substrates destined for lysosomes (kinetically
      defined late endosomes). These data demonstrate that CI-MPR takes a complex route
      that involves multiple sorting steps in both early and late endosomes.

PMID- 14595111
TI  - Delta F508 CFTR pool in the endoplasmic reticulum is increased by calnexin
      overexpression.
AB  - The most common cystic fibrosis transmembrane conductance regulator (CFTR) mutant
      in cystic fibrosis patients, Delta F508 CFTR, is retained in the endoplasmic
      reticulum (ER) and is consequently degraded by the ubiquitin-proteasome pathway
      known as ER-associated degradation (ERAD). Because the prolonged interaction of
      Delta F508 CFTR with calnexin, an ER chaperone, results in the ERAD of Delta F508
      CFTR, calnexin seems to lead it to the ERAD pathway. However, the role of
      calnexin in the ERAD is controversial. In this study, we found that calnexin
      overexpression partially attenuated the ERAD of Delta F508 CFTR. We observed the
      formation of concentric membranous bodies in the ER upon calnexin overexpression
      and that the Delta F508 CFTR but not the wild-type CFTR was retained in the
      concentric membranous bodies. Furthermore, we observed that calnexin
      overexpression moderately inhibited the formation of aggresomes accumulating the
      ubiquitinated Delta F508 CFTR. These findings suggest that the overexpression of
      calnexin may be able to create a pool of Delta F508 CFTR in the ER.

PMID- 14595112
TI  - A role for intermediate filaments in determining and maintaining the shape of
      nerve cells.
AB  - To date, the functions of most neural intermediate filament (IF) proteins have
      remained elusive. Peripherin is a type III intermediate filament (IF) protein
      that is expressed in developing and in differentiated neurons of the peripheral
      and enteric nervous systems. It is also the major IF protein expressed in PC12
      cells, a widely used model for studies of peripheral neurons. Dramatic increases
      in peripherin expression have been shown to coincide with the initiation and
      outgrowth of axons during development and regeneration, suggesting that
      peripherin plays an important role in axon formation. Recently, small interfering
      RNAs (siRNA) have provided efficient ways to deplete specific proteins within
      mammalian cells. In this study, it has been found that peripherin-siRNA depletes
      peripherin and inhibits the initiation, extension, and maintenance of neurites in
      PC12 cells. Furthermore, the results of these experiments demonstrate that
      peripherin IF are critical determinants of the overall shape and architecture of
      neurons.

PMID- 14595113
TI  - Sites of interaction between aldolase and thrombospondin-related anonymous
      protein in plasmodium.
AB  - Gliding motility and host cell invasion by apicomplexan parasites are empowered
      by an acto-myosin motor located underneath the parasite plasma membrane. The
      motor is connected to host cell receptors through trans-membrane invasins
      belonging to the thrombospondin-related anonymous protein (TRAP) family. A recent
      study indicates that aldolase bridges the cytoplasmic tail of MIC2, the
      homologous TRAP protein in Toxoplasma, and actin. Here, we confirm these
      unexpected findings in Plasmodium sporozoites and identify conserved features of
      the TRAP family cytoplasmic tail required to bind aldolase: a subterminal
      tryptophan residue and two noncontiguous stretches of negatively charged amino
      acids. The aldolase substrate and other compounds that bind to the active site
      inhibit its interaction with TRAP and with F-actin, suggesting that the function
      of the motor is metabolically regulated. Ultrastructural studies in salivary
      gland sporozoites localize aldolase to the periphery of the secretory micronemes
      containing TRAP. Thus, the interaction between aldolase and the TRAP tail takes
      place during or preceding the biogenesis of the micronemes. The release of their
      contents in the anterior pole of the parasite upon contact with the target cells
      should bring simultaneously aldolase, TRAP and perhaps F-actin to the proper
      subcellular location where the motor is engaged.

PMID- 14595114
TI  - Mechanism of human dermal fibroblast migration driven by type I collagen and
      platelet-derived growth factor-BB.
AB  - Migration of human dermal fibroblasts (HDFs) is critical for skin wound healing.
      The mechanism remains unclear. We report here that platelet-derived growth factor
      BB (PDGF-BB) is the major promotility factor in human serum for HDF motility on
      type I collagen. PDGF-BB recapitulates the full promotility activity of human
      serum and anti-PDGF neutralizing antibodies completely block it. Although
      collagen matrix initiates HDF migration without growth factors, PDGF-BB
      stimulated migration depends upon attachment of the cells to a collagen matrix.
      The PDGF-BB's role is to provide directionality and further enhancement for the
      collagen-initiated HDF motility. To study the collagen and PDGF-BB "dual
      signaling" in primary HDF, we establish "gene cassettes" plus lentiviral gene
      delivery approach, in which groups of genes are studied individually or in
      combination for their roles in HDF migration. Focal adhesion kinase,
      p21(Rac,CDC42)-activated kinase and Akt are grouped into an upstream kinase gene
      cassette, and the four major mitogen-activated protein kinases (extracellular
      signal-regulated kinase 1/2, p38, c-Jun NH2-terminal kinase, and extracellular
      signal-regulated kinase 5) are grouped into a downstream kinase gene cassette.
      The experiments demonstrate 1) the genes' individual roles and specificities, 2)
      their combined effects and sufficiency, and 3) the mechanisms of their
      intermolecular connections in HDF migration driven by collagen and PDGF-BB.

PMID- 14595115
TI  - Permissive roles of phosphatidyl inositol 3-kinase and Akt in skeletal myocyte
      maturation.
AB  - Skeletal muscle differentiation, maturation, and regeneration are regulated by
      interactions between signaling pathways activated by hormones and growth factors,
      and intrinsic genetic programs controlled by myogenic transcription factors,
      including members of the MyoD and myocyte enhancer factor 2 (MEF2) families.
      Insulin-like growth factors (IGFs) play key roles in muscle development in the
      embryo, and in the maintenance and hypertrophy of mature muscle in the adult, but
      the precise signaling pathways responsible for these effects remain incompletely
      defined. To study mechanisms of IGF action in muscle, we have developed a mouse
      myoblast cell line termed C2BP5 that is dependent on activation of the IGF-I
      receptor and the phosphatidyl inositol 3-kinase (PI3-kinase)-Akt pathway for
      initiation of differentiation. Here, we show that differentiation of C2BP5
      myoblasts could be induced in the absence of IGF action by recombinant
      adenoviruses expressing MyoD or myogenin, but it was reversibly impaired by the
      PI3-kinase inhibitor LY294002. Similar results were observed using a dominant
      negative version of Akt, a key downstream component of PI3-kinase signaling, and
      also were seen in C3H 10T1/2 fibroblasts. Inhibition of PI3-kinase did not
      prevent accumulation of muscle differentiation-specific proteins (myogenin,
      troponin T, or myosin heavy chain), did not block transcriptional activation of E
      box containing muscle reporter genes by MyoD or myogenin, and did not inhibit the
      expression or function of endogenous MEF2C or MEF2D. An adenovirus encoding
      active Akt could partially restore terminal differentiation of MyoD-expressing
      and LY294002-treated myoblasts, but the resultant myofibers contained fewer
      nuclei and were smaller and thinner than normal, indicating that another PI3
      kinase-stimulated pathway in addition to Akt is required for full myocyte
      maturation. Our results support the idea that an IGF-regulated PI3-kinase pathway
      functions downstream of or in parallel with MyoD, myogenin, and MEF2 in muscle
      development to govern the late steps of differentiation that lead to
      multinucleated myotubes.

PMID- 14595116
TI  - Two phases of actin polymerization display different dependencies on PI(3,4,5)P3
      accumulation and have unique roles during chemotaxis.
AB  - The directional movement of cells in chemoattractant gradients requires
      sophisticated control of the actin cytoskeleton. Uniform exposure of
      Dictyostelium discoideum amoebae as well as mammalian leukocytes to
      chemoattractant triggers two phases of actin polymerization. In the initial rapid
      phase, motility stops and the cell rounds up. During the second slow phase,
      pseudopodia are extended from local regions of the cell perimeter. These
      responses are highly correlated with temporal and spatial accumulations of
      PI(3,4,5)P3/PI(3,4)P2 reflected by the translocation of specific PH domains to
      the membrane. The slower phase of PI accumulation and actin polymerization is
      more prominent in less differentiated, unpolarized cells, is selectively
      increased by disruption of PTEN, and is relatively more sensitive to
      perturbations of PI3K. Optimal levels of the second responses allow the cell to
      respond rapidly to switches in gradient direction by extending lateral
      pseudopods. Consequently, PI3K inhibitors impair chemotaxis in wild-type cells
      but partially restore polarity and chemotactic response in pten- cells.
      Surprisingly, the fast phase of PI(3,4,5)P3 accumulation and actin
      polymerization, which is relatively resistant to PI3K inhibition, can support
      inefficient but reasonably accurate chemotaxis.

PMID- 14595117
TI  - DWWA, a novel protein containing two WW domains and an IQ motif, is required for
      scission of the residual cytoplasmic bridge during cytokinesis in Dictyostelium.
AB  - We have identified a novel gene, dwwA, which is required for cytokinesis of
      Dictyostelium cells on solid surfaces. Its product, Dd WW domain containing
      protein A (DWWA), contains several motifs, including two WW domains, an IQ motif,
      a C2 domain, and a proline-rich region. On substrates, cells lacking dwwA were
      multinucleated and larger and flatter than wild-type cells due to their frequent
      inability to sever the cytoplasmic bridge connecting daughter cells after
      mitosis. When cultured in suspension, however, dwwA-null cells seemed to carry
      out cytokinesis normally via a process not driven by the shearing force arising
      from agitation of the culture. GFP-DWWA localized to the cell cortex and nucleus;
      analysis of the distributions of various truncation mutants revealed that the N
      terminal half of the protein, which contains the C2 domain, is required for the
      cortical localization of DWWA. The IQ motif of DWWA binds calmodulin in vitro.
      Given that the scission process is also defective in calmodulin knockdown cells
      cultured on substrates (Liu et al., 1992), we propose that DWWA's multiple
      binding domains enable it to function as an adaptor protein, facilitating the
      scission process through the regulation of Ca(2+)/calmodulin-mediated remodeling
      of the actin cytoskeleton and/or modulation of membrane dynamics.

PMID- 14595118
TI  - Novel membrane protein shrew-1 targets to cadherin-mediated junctions in
      polarized epithelial cells.
AB  - While searching for potential candidate molecules relevant for the pathogenesis
      of endometriosis, we discovered a 2910-base pair cDNA encoding a novel putative
      411-amino acid integral membrane protein that we called shrew-1. The putative
      open-reading frame was confirmed with antibodies against shrew-1 peptides that
      labeled a protein of approximately 48 kDa in extracts of shrew-1 mRNA-positive
      tissue and also detected ectopically expressed shrew-1. Expression of epitope
      tagged shrew-1 in epithelial cells and analysis by surface biotinylation and
      immunoblots demonstrated that shrew-1 is indeed a transmembrane protein. Shrew-1
      is able to target to E-cadherin-mediated adherens junctions and interact with the
      E-cadherin-catenin complex in polarized MCF7 and Madin-Darby canine kidney cells,
      but not with the N-cadherin-catenin complex in nonpolarized epithelial cells.
      Direct interaction of shrew-1 with beta-catenin in in vitro pull-down assay
      suggests that beta-catenin might be one of the proteins that targets and/or
      retains shrew-1 in the adherens junctions. Interestingly, shrew-1 was partially
      translocated in response to scatter factor (ligand of receptor tyrosine kinase c
      met) from the plasma membrane to the cytoplasm where it still colocalized with
      endogenous E-cadherin. In summary, we introduce shrew-1 as a novel component of
      adherens junctions, interacting with E-cadherin-beta-catenin complexes in
      polarized epithelial cells.

PMID- 14595119
TI  - The cyclase-associated protein CAP as regulator of cell polarity and cAMP
      signaling in Dictyostelium.
AB  - Cyclase-associated protein (CAP) is an evolutionarily conserved regulator of the
      G-actin/F-actin ratio and, in yeast, is involved in regulating the adenylyl
      cyclase activity. We show that cell polarization, F-actin organization, and
      phototaxis are altered in a Dictyostelium CAP knockout mutant. Furthermore, in
      complementation assays we determined the roles of the individual domains in
      signaling and regulation of the actin cytoskeleton. We studied in detail the
      adenylyl cyclase activity and found that the mutant cells have normal levels of
      the aggregation phase-specific adenylyl cyclase and that receptor-mediated
      activation is intact. However, cAMP relay that is responsible for the generation
      of propagating cAMP waves that control the chemotactic aggregation of starving
      Dictyostelium cells was altered, and the cAMP-induced cGMP production was
      significantly reduced. The data suggest an interaction of CAP with adenylyl
      cyclase in Dictyostelium and an influence on signaling pathways directly as well
      as through its function as a regulatory component of the cytoskeleton.

PMID- 14595121
TI  - Epithelial colonies cultured from human explanted liver in subacute hepatic
      failure exhibit hepatocyte, biliary epithelial, and stem cell phenotypic markers.
AB  - The liver in subacute hepatic failure may become enriched for hepatic progenitor
      cells. Liver tissue from such a patient was collagenase digested and, from the
      nonparenchymal cell fraction, epithelioid colonies were developed. Albumin and
      alpha-1-antitrypsin (AAT) were secreted for greater than 120 days from these
      colonies. Reverse transcription-polymerase chain reaction showed expression of
      markers of both hepatocyte and biliary epithelial phenotypes (cytokeratins 7, 18,
      and 19, albumin and AAT, hepatocyte growth factor receptor, transforming growth
      factor beta receptor type II, gamma-glutamyl transpeptidase, biliary
      glycoprotein). The cell cycle regulator p21 was also expressed. The POU domain
      transcription factor octamer-binding protein 4 was present in these cells, but
      not in RNA or cDNA prepared from adult human liver. These markers were maintained
      even after 165 days culture. Proliferating epithelial-like cells with combined
      hepatocyte- and biliary-epithelial-specific functional markers and a stem cell
      marker can be isolated from the nonparenchymal fraction of liver cells in
      subacute hepatic failure.

PMID- 14595120
TI  - Transforming growth factor-beta 1 induces apoptosis through Fas ligand
      independent activation of the Fas death pathway in human gastric SNU-620
      carcinoma cells.
AB  - To date, two major apoptotic pathways, the death receptor and the mitochondrial
      pathway, have been well documented in mammalian cells. However, the involvement
      of these two apoptotic pathways, particularly the death receptor pathway, in
      transforming growth factor-beta 1 (TGF-beta 1)-induced apoptosis is not well
      understood. Herein, we report that apoptosis of human gastric SNU-620 carcinoma
      cells induced by TGF-beta 1 is caused by the Fas death pathway in a Fas ligand
      independent manner, and that the Fas death pathway activated by TGF-beta 1 is
      linked to the mitochondrial apoptotic pathway via Bid mediation. We showed that
      TGF-beta 1 induced the expression and activation of Fas and the subsequent
      caspase-8-mediated Bid cleavage. Interestingly, expression of dominant negative
      FADD and treatment with caspase-8 inhibitor efficiently prevented TGF-beta 1
      induced apoptosis, whereas the treatment with an activating CH11 or a
      neutralizing ZB4 anti-Fas antibody, recombinant Fas ligand, or Fas-Fc chimera did
      not affect activation of Fas and the subsequent induction of apoptosis by TGF
      beta 1. We further demonstrated that TGF-beta 1 also activates the mitochondrial
      pathway showing Bid-mediated loss of mitochondrial membrane potential and
      subsequent cytochrome c release associated with the activations of caspase-9 and
      the effector caspases. Moreover, all these apoptotic events induced by TGF-beta 1
      were found to be effectively inhibited by Smad3 knockdown and also completely
      abrogated by Smad7 expression, suggesting the involvement of the Smad3 pathway
      upstream of the Fas death pathway by TGF-beta 1.

PMID- 14595122
TI  - Engineered zinc finger proteins for controlling stem cell fate.
AB  - Stem cells are functionally defined as progenitor cells that can self-renew and
      differentiate. Critical transitions in these cells are controlled via signaling
      pathways and subsequent transcriptional regulation. Technologies capable of
      modulating the levels of gene expression, especially those of transcription
      factors, represent powerful tools for research and could potentially be used in
      therapeutic applications. In this study, we evaluated the ability of synthetic
      zinc finger protein transcription factors (ZFP-TFs) to cause the differentiation
      of embryonic stem (ES) cells. We constructed ZFP-TFs that target the mouse Oct-4
      gene (which is a major regulator of ES cell pluripotency and self-renewal). These
      designed transcription factors were able to regulate the transcription of Oct-4,
      affecting the expression of downstream genes and thus regulating ES cell
      differentiation.

PMID- 14595123
TI  - A novel route of transplantation of human cord blood stem cells in preimmune
      fetal sheep: the intracelomic cavity.
AB  - The intracelomic route for in utero hematopoietic stem cell transplantation was
      evaluated in preimmune fetal sheep and the engraftment characteristics were
      defined. Twelve twin ovine fetuses (gestational age: 40-45 days) received
      intracelomic transplants of human CD3-depleted (50 x 10(6) per lamb) or CD34
      selected (1-2 x 10(5) per lamb) cord blood hematopoietic stem cells. Engraftment
      was evaluated from cell suspensions of the liver, spleen, bone marrow, and thymus
      by flow cytometry, cloning assays, and polymerase chain reaction (PCR) analyses
      of human beta2-microglobulin. Four fetuses (33%) aborted shortly after
      intracelomic transplantation and were not evaluable for engraftment. Engraftment
      was detected in four fetuses obtained from cesarean delivery on day 70 after
      transplantation of CD3-depleted cord blood cells. The degrees of engraftment in
      these four fetuses ranged from 6%-22% in the different organs (as revealed by
      antigenic analysis of human CD45 with flow cytometry). Three fetuses obtained
      after cesarean section at 102 (no. 435184) and 105 (no. 915293, no. 037568) days
      and one fetus delivered at term that received CD34-selected cord blood cells had
      human engraftment with 10%, 32%, 20%, and 10% CD45(+) cells in bone marrow,
      respectively. In six of eight fetuses evaluable for human engraftment, chimerism
      was confirmed by PCR analysis for human beta2-microglobulin, which also
      identified human cells in brain, spinal cord, heart, lung, and skeletal muscle.
      This preliminary study indicates that intracelomic transplantation of human
      hematopoietic stem cells in fetal lambs is feasible and effective in terms of
      hematopoietic engraftment.

PMID- 14595125
TI  - Telomere length in subpopulations of human hematopoietic cells.
AB  - In order to test the hypothesis that the telomere length in human hematopoietic
      cells correlates with their proliferative potential, we analyzed the telomere
      length in highly purified subpopulations of bone marrow cells. Cells were sorted
      on the basis of CD34 and CD38 cell surface markers, and two samples were
      additionally sorted on the basis of Hoechst 33342 dye efflux allowing isolation
      of side population (SP) cells. The telomere length in limiting numbers of sorted
      cells was analyzed using a newly developed fluorescence in situ hybridization
      (flow-FISH) method in which hybridization of telomere probe in cells of interest
      is measured relative to control cells in the same tube. In all seven bone marrow
      samples analyzed, the telomere length in CD34(+)CD38(-) cells was longer than in
      CD34(+)CD38(+) cells from the same donor (p < 0.02). Results with sorted SP cells
      were less clear: the telomere fluorescence in these cells was very heterogeneous,
      and a reproducible difference in telomere length relative to CD34(+)CD38(-) cells
      could not be observed. We conclude that the telomere length in subpopulations of
      hematopoietic cells does appear to be correlated with the known proliferative
      potential of such cells and that further characterization of cells on the basis
      of telomere length is warranted for enrichment of very rare precursors of
      hematopoietic and other tissues.

PMID- 14595124
TI  - Stable expression of hrGFP by mouse embryonic stem cells: promoter activity in
      the undifferentiated state and during dopaminergic neural differentiation.
AB  - Three promoters, cellular polypeptide chain elongation factor 1 alpha (EF1),
      cytomegalovirus (CMV), and Rous sarcoma virus (RSV) were examined for stable
      transgene expression in mouse embryonic stem (ES) cells and their progeny during
      dopaminergic neural differentiation. In undifferentiated ES cells the EF1
      promoter was highly effective, while CMV had moderate activity. After 3 months in
      culture, expression of humanized renilla green fluorescent protein (hrGFP) was
      unchanged for the EF1 promoter and decreased for CMV. At the nestin-positive
      stage of differentiation, hrGFP and nestin were colocalized in about 20% of cells
      for EF1, in contrast to 80% of cells for the CMV promoter. In tyrosine
      hydroxylase (TH)-positive neurons neither the EF1 nor CMV promoter were
      effective. The RSV promoter was inactive in undifferentiated, nestin-positive,
      and TH-positive cells. Thus, EF1 and CMV are effective promoters for transgene
      expression in undifferentiated ES cells and nestin-positive neural precursors.

PMID- 14595126
TI  - The profile of gene expression of human marrow mesenchymal stem cells.
AB  - Mesenchymal stem cells (MSCs) are multipotent precursors present in adult bone
      marrow, that differentiate into osteoblasts, adipocytes and myoblasts, and play
      important roles in hematopoiesis. We examined gene expression of these cells by
      serial analysis of gene expression, and found that collagen I, secreted protein
      acidic and rich in cysteine (osteonectin), transforming growth factor beta- (TGF
      beta) induced, cofilin, galectin-1, laminin-receptor 1, cyclophilin A, and matrix
      metalloproteinase-2 are among the most abundantly expressed genes. Comparison
      with a library of CD34(+) cells revealed that MSCs had a larger number of
      expressed genes in the categories of cell adhesion molecule, extracellular and
      development. The two types of cells share abundant transcripts of many genes,
      some of which are highly expressed in myeloid progenitors (thymosin-beta 4 and
      beta 10, fos and jun). Interleukin-11 (IL-11), IL-15, IL-27 and IL-10R, IL-13R
      and IL-17R were the most expressed genes among the cytokines and their receptors
      in MSCs, and various interactions can be predicted with the CD34(+) cells. MSCs
      express several transcripts for various growth factors and genes suggested to be
      enriched in stem cells. This study reports the profile of gene expression in MSCs
      and identifies the important contribution of extracellular protein products,
      adhesion molecules, cell motility, TGF-beta signaling, growth factor receptors,
      DNA repair, protein folding, and ubiquination as part of their transcriptome.

PMID- 14595127
TI  - Discrete types of osteoclast precursors can be generated from embryonic stem
      cells.
AB  - Osteoclast precursors (OCPs) share some characteristics with the
      monocyte/macrophage lineages, but the early events of OCP development are not yet
      clear. To investigate osteoclastogenesis from the earliest stage, we used step
      wise cultures of embryonic stem (ES) cells to induce mature osteoclasts and
      assessed the effect of vascular endothelial growth factor receptor (VEGFR)-1/Fc
      chimeric protein on osteoclast development. Addition of VEGFR-1/Fc for the first
      5 days of culture (phase I) severely inhibited the development of OCPs. Although
      OCPs were detected after culturing for a further 5 days (phase II), the reduction
      of OCPs in phase I was maintained in phase II. The generation of OCPs in phase I
      was resistant to signal blocking mediated by Kit receptors, but that in phase II
      was partially inhibited by either an anti-Kit antagonistic antibody or VEGFR-1/Fc
      and was severely inhibited by the combination of both reagents. Moreover, the
      OCPs in phase I gave rise to larger numbers of osteoclasts but required a longer
      period for maturation than the OCPs in phase II. We thus showed that OCPs
      expanded in phase II, but the majority of OCPs arose from ES cells in a manner
      dependent on VEGFR-1 binding factor(s) in phase I.

PMID- 14595128
TI  - Characterization of multipotential mesenchymal progenitor cells derived from
      human trabecular bone.
AB  - The in vitro culture of human trabecular bone-derived cells has served as a
      useful system for the investigation of the biology of osteoblasts. The recent
      discovery in our laboratory of the multilineage mesenchymal differentiation
      potential of cells derived from collagenase-treated human trabecular bone
      fragments has prompted further interest in view of the potential application of
      mesenchymal progenitor cells (MPCs) in the repair and regeneration of tissue
      damaged by disease or trauma. Similar to human MPCs derived from bone marrow, a
      clearer understanding of the variability associated with obtaining these bone
      derived cells is required in order to optimize the design and execution of
      applicable studies. In this study, we have identified the presence of a CD73(+),
      STRO-1(+), CD105(+), CD34(-), CD45(-), CD144(-) cell population resident within
      collagenase-treated, culture-processed bone fragments, which upon migration
      established a homogeneous population of MPCs. Additionally, we have introduced a
      system of culturing these MPCs that best supports and maintains their optimal
      differentiation potential during long-term culture expansion. When cultured as
      described, the trabecular bone-derived cells display stem cell-like capabilities,
      characterized by a stable undifferentiated phenotype as well as the ability to
      proliferate extensively while retaining the potential to differentiate along the
      osteoblastic, adipocytic, and chondrocytic lineages, even when maintained in long
      term in vitro culture.

PMID- 14595129
TI  - Cobblestone area-forming cells in human cord blood are heterogeneous and differ
      from long-term culture-initiating cells.
AB  - The long-term culture-initiating cell (LTC-IC) assay is a physiological approach
      to the quantitation of primitive human hematopoietic cells. The readout using
      identification of cobblestone area-forming cells (CAFC) has gained popularity
      over the LTC-IC readout where cells are subcultured in a colony-forming cell
      assay. However, comparing the two assays, cord blood (CB) mononuclear cell (MNC)
      samples were found to contain a higher frequency of CAFC than LTC-IC (126 +/- 83
      versus 40 +/- 31 per 10(5) cells, p = 0.0001). Overall, 60% of week-5
      cobblestones produced by CB MNC were not functional LTC-IC and were classified as
      "false." Separation of CB MNC using immunomagnetic columns showed that false
      cobblestones were CD34(-)/lineage(+). Purified CD34(+) cells, as expected, gave
      very similar readouts in the two assays, with 4,084 and 3,468/10(5) cells being
      CAFC and LTC-IC, respectively. CD34(-)/lineage(-) cells did not form cobblestones
      or become CD34(+) on stroma or in cytokine culture. Human CB MNC contain a
      population of mature lineage(+) cells, possibly mature T or B cells, which,
      although producing cobblestone areas (CA), are not functional LTC-IC. The CAFC
      readout by this method, therefore, is unreliable for estimation of primitive
      hematopoietic cells by limiting dilution analysis in whole human CB or MNC and
      also may not detect CD34(-) CA stem cells.

PMID- 14595130
TI  - The molecular perspective: epidermal growth factor.

PMID- 14595131
TI  - Which US microbubble contrast agent is best for gene therapy?

PMID- 14595132
TI  - The digital rEvolution: the millennial change in medical imaging.

PMID- 14595133
TI  - Primer on multiple regression models for diagnostic imaging research.
AB  - This article provides an introduction to multiple regression analysis and its
      application in diagnostic imaging research. We begin by examining why multiple
      regression models are needed in the evaluation of diagnostic imaging
      technologies. We then examine the broad categories of available models, notably
      multiple linear regression models for continuous outcomes and logistic regression
      models for binary outcomes. The purpose of this article is to elucidate the
      scientific logic, meaning, and interpretation of multiple regression models by
      using examples from the diagnostic imaging literature.

PMID- 14595134
TI  - Driving market-driven engineering.

PMID- 14595135
TI  - Knowledge sharing in radiology.

PMID- 14595137
TI  - Screening for cancer: when is it valid?--Lessons from the mammography experience.
AB  - There is increasing interest in the development of imaging tests to screen for
      diseases such as cancer. Mammographic screening for breast cancer has undergone
      greater scrutiny than any other test. Many important lessons have been learned
      from the issues that have been raised with regard to mammographic screening.
      Those interested in developing new screening tests can learn from the mammography
      experience.

PMID- 14595138
TI  - Assessment of the patient with hyperacute stroke: imaging and therapy.
AB  - Neuroimaging is an important part of the assessment of patients with hyperacute
      stroke. As new treatments that may reverse cerebral ischemia have been developed,
      the role of neuroimaging has changed from simply anatomic depiction of early
      infarction to identification, by means of physiologic (rather than simply
      anatomic) information, of regions that are at risk for infarction. The goal of
      such imaging techniques is to monitor successes and complications of recently
      developed treatments such as thrombolysis.

PMID- 14595142
TI  - Case 64: Tuberous sclerosis.

PMID- 14595139
TI  - Liliequist membrane: three-dimensional constructive interference in steady state
      MR imaging.
AB  - PURPOSE: To evaluate the Liliequist membrane in healthy volunteers by using three
      dimensional (3D) Fourier transformation constructive interference in steady state
      (CISS) magnetic resonance (MR) imaging. MATERIALS AND METHODS: In 31 volunteers,
      the authors performed 3D CISS MR imaging. They divided the membrane into three
      segments: the sellar, diencephalic, and mesencephalic segments. MR images were
      evaluated to identify the segments, superior and inferior attachments, lateral
      border, and thickness of the Liliequist membrane. RESULTS: Three-dimensional CISS
      MR imaging depicted the sellar, diencephalic, and mesencephalic segments of the
      Liliequist membrane in the sagittal plane in 25 (81%), 16 (52%), and five (16%)
      of the 31 subjects, respectively. Transverse MR imaging depicted these segments
      in 24 (77%), 10 (32%), and two (6%) subjects, respectively, and coronal MR
      imaging depicted them in 24 (77%), 12 (39%), and two (6%) subjects, respectively.
      Clear attachment of the membrane to the dorsum sellae was observed in 22 (88%) of
      25 subjects in whom the sellar segment was identified. Clear attachment to the
      mamillary body was identified in eight (50%) of 16 subjects in whom the
      diencephalic segment was identified. The Liliequist membrane was attached to the
      oculomotor nerve on seven (14%) of 50 sides of the lateral border and to the
      arachnoid membrane around the oculomotor nerve on 28 (56%) sides. In the sagittal
      plane, the thickness of the membrane was less than one-half the thickness of the
      third ventricle floor in 22 (88%) of 25 subjects. CONCLUSION: The Liliequist
      membrane can be visualized by using 3D CISS MR sequences.

PMID- 14595143
TI  - Objective criteria of triangular cord sign in biliary atresia on US scans.
AB  - PURPOSE: To develop objective criteria for the ultrasonographic (US) appearance
      of the triangular cord (TC) sign for the diagnosis of biliary atresia. MATERIALS
      AND METHODS: US was performed in 86 infants with jaundice. Biliary atresia (n =
      20) was confirmed with hepatoportoenterostomy. Neonatal hepatitis (n = 66) was
      diagnosed with needle biopsy (n = 5), cholescintigraphy (n = 19), or clinical
      findings (n = 42). Thickness of the echogenic anterior wall of the right portal
      vein (EARPV) was measured. The TC sign was defined as thickness of the EARPV of
      more than 4 mm on a longitudinal scan. Biliary atresia was diagnosed when the TC
      sign was present. Statistical analyses were performed to compare the thickness of
      the EARPV between patients with biliary atresia and those with neonatal hepatitis
      and to test the significance of a 4-mm thickness as the criterion for the TC sign
      in the differentiation of biliary atresia from neonatal hepatitis (P <.05).
      RESULTS: The TC sign was present in 16 (80%) of 20 patients with biliary atresia
      and in one of 66 patients with neonatal hepatitis. Mean thickness of the EARPV
      was significantly greater in patients with biliary atresia (5.39 mm) than in
      patients with neonatal hepatitis (2.17 mm) (P <.05). Use of 4-mm thickness as the
      criterion for TC sign was statistically significant (P <.05), resulting in a
      sensitivity of 80%, specificity of 98%, and positive and negative predictive
      values of 94% for the diagnosis of biliary atresia. CONCLUSION: An objective
      criterion of the TC sign is an EARPV thicker than 4 mm on a longitudinal scan.

PMID- 14595144
TI  - Multi-detector row CT of relevant vascular anatomy of the surgical plane in split
      liver transplantation.
AB  - PURPOSE: To evaluate relevant arterial and venous anatomy of the hepatectomy
      plane lateral to segment IV by using multi-detector row computed tomography (CT)
      with respect to adult living related transplantation of the right lobe of the
      liver. MATERIALS AND METHODS: In potential liver donors, 100 consecutive hepatic
      CT angiograms were obtained after intravenous bolus administration of 150-180 mL
      of nonionic contrast material. Arterial phase images (1.25-mm collimation, 7.5
      mm/ 0.8-second table speed) were acquired after test dose injection. Portal phase
      images were acquired at 60 seconds (2.5-mm collimation, 15 mm/0.8-second table
      speed). Postprocessing depicted arterial, portal, and hepatic vein anatomy
      traversing the anticipated surgical hepatectomy plane to the right of the middle
      hepatic vein (MHV) and separating the right and left lobes of the liver. Two
      radiologists interpreted the images, and data were agreed on by consensus. Data
      collected included intrahepatic anatomy and origin of the artery and vein
      supplying segment IV; the venous drainage from segments V and VIII; and the
      presence, size, and distance from the right hepatic vein (RHV) confluence of
      accessory hepatic veins in the surgical plane. RESULTS: Thirty-one donors had
      conventional hepatic vascular anatomy. Vessels that traversed the hepatectomy
      plane included the artery supplying segment IV in seven (7%) patients, dominant
      portal vein supply to segment IV from the right portal vein in two (2%) patients
      or from both right and left portal vein branches in three (3%) patients, segment
      VIII draining into the MHV in 67 (67%) patients or both the MHV and RHV in 18
      (18%) patients (the major draining vein was >7 mm in diameter in 23%), segment V
      draining into the MHV in 10 (10%) patients, or both the MHV and RHV in 19 (19%)
      patients (the major draining vein from segment V was 7-10 mm in diameter in 70
      patients, and larger than 10 mm in five). Forty-four accessory hepatic veins were
      identified in 40 patients; seven drained segment V, while the majority drained
      segments VI and VII. The mean diameter was 5.3 mm and 45% were larger than 6 mm.
      The average distance to the RHV-inferior vena cava confluence was 28.7 mm. Of 70
      patients with drainage from segment V into RHV, 22 (31%) had an accessory RHV.
      However, atypical drainage into the MHV was noted in seven (70%) of 10 patients
      and into the MHV and RHV in 11 (58%) of 19 patients. CONCLUSION: In the majority
      of potential donors, CT angiography depicted a wide range of vascular anatomic
      variations that traverse the hepatectomy plane.

PMID- 14595145
TI  - CT predictors of failed laparoscopic appendectomy.
AB  - PURPOSE: To identify computed tomographic (CT) signs that may help predict
      possible failure of laparoscopic appendectomy and subsequent conversion to open
      appendectomy. MATERIALS AND METHODS: Of 234 consecutive patients who underwent
      preoperative CT and in whom laparoscopic appendectomy was attempted, 26 required
      conversion to open appendectomy. Conversion was correlated with the following CT
      findings: appendix location, appendicolith, cecal wall thickening involving the
      base of the appendix, lymphadenopathy, and appendiceal diameter. The extent of
      inflammation was graded by using a six-point scale: 0 meant normal appendix; 1,
      possibly abnormal appendix (6-mm diameter without other abnormality); 2, abnormal
      appendix (diameter > or = 6 mm with wall enhancement) without adjacent fat
      stranding; 3, abnormal appendix surrounded by fat stranding; 4, abnormal appendix
      surrounded by fat stranding and fluid; and 5, inflammatory mass or abscess.
      Student t and chi2 tests were used for statistical analysis of interval and
      nominal values, respectively. RESULTS: Although there was a significant
      difference in appendiceal diameter between the patients in whom laparoscopic
      appendectomy was successfully completed (11.3 mm +/- 3.5 [SD]) and those who
      required conversion (12.9 mm +/- 3.9), no distinct cutoff point was identified.
      Of the five CT findings evaluated, none was a significant predictor of conversion
      to open appendectomy. Eleven (7%) of 164 patients with a CT inflammation grade of
      0-3 required conversion, whereas 15 (21%) of 70 patients with a grade of 4 or 5
      required conversion (P <.04). CONCLUSION: The majority of patients with
      appendicitis can be treated with laparoscopic appendectomy. Nevertheless,
      patients who require conversion to open appendectomy tend to have high CT
      inflammation grades of 4 or 5, which indicate the presence of periappendiceal
      fluid or an inflammatory mass or abscess.

PMID- 14595146
TI  - The antral pad sign.

PMID- 14595147
TI  - Gadopentetate dimeglumine versus ultrasmall superparamagnetic iron oxide for
      dynamic contrast-enhanced MR imaging of tumor angiogenesis in human colon
      carcinoma in mice.
AB  - PURPOSE: To compare the kinetic physiologic properties of a clinical contrast
      agent, gadopentetate dimeglumine, with those of ultrasmall superparamagnetic iron
      oxide (USPIO) particles for dynamic contrast material-enhanced magnetic resonance
      (MR) imaging of tumor angiogenesis in human colon carcinoma in mice with a
      clinical MR imaging unit. MATERIALS AND METHODS: Thirty-two mice with human colon
      carcinoma were injected with either gadopentetate dimeglumine (n = 16) or USPIO
      (n = 16) for dynamic contrast-enhanced MR imaging and pre- and postcontrast T2
      and T2* measurements. Dynamic contrast-enhanced MR imaging measurements were
      analyzed by using a two-compartment model to calculate the endothelial transfer
      coefficient surface area product (KPS) for the tumor microvasculature, the reflux
      coefficient (k), and the fractional plasma volume (fPV). KPS, k, and fPV maps
      were compared with histologic microvessel density (MVD) and used to observe
      differences between core and rim regions of tumor. RESULTS: Results in 30 mice
      (15 in the gadopentetate dimeglumine group and 15 in the USPIO group) could be
      used. KPS values measured with both agents correlated well with MVD in hot spots
      (gadopentetate dimeglumine: r = 0.6, P =.02; USPIO: r = 0.6, P =.01). No
      significant difference (P =.4) in correlation was found between the two agents.
      Both USPIO and gadopentetate dimeglumine demonstrated higher MVD and KPS values
      in tumor rim than in tumor core (P <.01). Tumor k values correlated poorly with
      whole-tumor MVD for both gadopentetate dimeglumine (r = 0.3, P =.4) and USPIO (r
      = 0.2, P =.6), while fPV values correlated well with whole-tumor MVD for USPIO (r
      = 0.6, P =.02) but not gadopentetate dimeglumine (r = -0.01, P =.98). T2 and T2*
      measurements showed small differences between areas of high and low angiogenic
      activity with both agents. CONCLUSION: The kinetic physiologic properties of
      gadopentetate dimeglumine are as good as those of USPIO for dynamic contrast
      enhanced MR imaging for calculating KPS as a measurement of angiogenesis in human
      colon carcinoma. Further studies with patients may reveal whether gadopentetate
      dimeglumine might be used for this purpose in clinical practice.

PMID- 14595149
TI  - CT-guided transthoracic needle aspiration biopsy of pulmonary nodules: needle
      size and pneumothorax rate.
AB  - PURPOSE: To evaluate the effect of coaxial needle size on pneumothorax rate and
      the diagnostic accuracy of computed tomography (CT)-guided transthoracic needle
      aspiration biopsy (TNAB) of pulmonary nodules. MATERIALS AND METHODS:
      Retrospective review of 846 consecutive CT-guided TNAB procedures was performed.
      A coaxial approach was implemented in all patients by using an 18- or 19-gauge
      outer stabilizing needle through which a smaller aspiration needle or automated
      biopsy gun was inserted for tissue sampling. Univariate and multivariate
      regression analyses were used to analyze coaxial needle size, age, sex, smoking
      history, lesion size, use of an automated core biopsy gun, number of needle
      passes, and frequency of chest tube placement. Sensitivity, specificity, and
      diagnostic accuracy were calculated for 676 patients with at least 18 months of
      clinical follow-up. RESULTS: Pneumothorax occurred in 226 of 846 patients.
      Coaxial needle size and patient age had a significant effect on pneumothorax
      rate. Pneumothorax occurred in 124 (38%) of 324 patients who underwent procedures
      with 18-gauge needles and in 121 (23%) of 522 patients who underwent procedures
      with 19-gauge needles (P <.001). The overall diagnostic accuracy was 96% for
      procedures performed with 18-gauge needles and 92% for procedures performed with
      19-gauge needles, with a sensitivity of 95% and 89% and a specificity of 100% and
      99%, respectively. Pneumothorax occurred in 153 patients older than 60 years, in
      99 patients 60 years and younger (P <.02), in 90 patients older than 70 years,
      and in 162 patients younger than 70 years (P <.01). The relationship between
      pneumothorax rate and age as a continuous distribution was not significant (P
      <.07), nor were the 50- or 75-year age cutoffs (P <.06 and P <.9, respectively).
      CONCLUSION: Use of a smaller coaxial stabilizing needle produces a substantially
      decreased risk of pneumothorax with comparable diagnostic accuracy, sensitivity,
      and specificity for histopathologic diagnosis of pulmonary nodules.

PMID- 14595148
TI  - Evaluation of peripheral arterial bypass grafts with multi-detector row CT
      angiography: comparison with duplex US and digital subtraction angiography.
AB  - PURPOSE: To assess the technical feasibility of multi-detector row computed
      tomographic (CT) angiography in the assessment of peripheral arterial bypass
      grafts and to evaluate its accuracy and reliability in the detection of graft
      related complications, including graft stenosis, aneurysmal changes, and
      arteriovenous fistulas. MATERIALS AND METHODS: Four-channel multi-detector row CT
      angiography was performed in 65 consecutive patients with 85 peripheral arterial
      bypass grafts. Each bypass graft was divided into three segments (proximal
      anastomosis, course of the graft body, and distal anastomosis), resulting in 255
      segments. Two readers evaluated all CT angiograms with regard to image quality
      and the presence of bypass graft-related abnormalities, including graft stenosis,
      aneurysmal changes, and arteriovenous fistulas. The results were compared with
      McNemar test with Bonferroni correction. CT attenuation values were recorded at
      five different locations from the inflow artery to the outflow artery of the
      bypass graft. These findings were compared with the findings at duplex
      ultrasonography (US) in 65 patients and the findings at conventional digital
      subtraction angiography (DSA) in 27. RESULTS: Image quality was rated as good or
      excellent in 250 (98%) and in 252 (99%) of 255 bypass segments, respectively.
      There was excellent agreement both between readers and between CT angiography and
      duplex US in the detection of graft stenosis, aneurysmal changes, and
      arteriovenous fistulas (kappa = 0.86-0.99). CT angiography and duplex US were
      compared with conventional DSA, and there was no statistically significant
      difference (P >.25) in sensitivity or specificity between CT angiography and
      duplex US for both readers for detection of hemodynamically significant bypass
      stenosis or occlusion, aneurysmal changes, or arteriovenous fistulas. Mean CT
      attenuation values ranged from 232 HU in the inflow artery to 281 HU in the
      outflow artery of the bypass graft. CONCLUSION: Multi-detector row CT angiography
      may be an accurate and reliable technique after duplex US in the assessment of
      peripheral arterial bypass grafts and detection of graft-related complications,
      including stenosis, aneurysmal changes, and arteriovenous fistulas.

PMID- 14595150
TI  - Severe acute respiratory syndrome: radiographic evaluation and clinical outcome
      measures.
AB  - PURPOSE: To evaluate the relationship among chest radiographs, oxygen
      supplementation requirement, and treatment response in severe acute respiratory
      syndrome (SARS). MATERIALS AND METHODS: Forty patients (20 women, 20 men; mean
      age, 42.90 years +/- 14.01 [SD]; median age, 41.5 years; age range, 25-82 years)
      with SARS were evaluated. Daily chest radiographs were graded according to
      percentage of lung involvement during 20.15 days +/- 5.56 (median, 20 days;
      range, 14-38 days). Times between symptoms and treatment and time to reach
      maximal radiographic score from admission and treatment day were determined.
      Daily oxygen saturation (Sao2) and oxygen supplementation including mechanically
      assisted ventilation were recorded. Treatment response was defined as good, fair,
      and poor. Patterns of radiographic opacity at admission and at maximal
      radiographic score were noted. Differences in radiographic and clinical
      parameters with respect to oxygen supplementation and treatment response were
      respectively evaluated with Mann-Whitney and Kruskal-Wallis tests. RESULTS:
      Larger maximal radiographic scores, lower Sao2 at maximal radiographic change,
      longer time from treatment to maximal radiographic score (P <.01), and diffuse
      consolidation at maximal radiographic score were associated with oxygen
      supplementation. Parameters that influenced treatment response were time from
      symptom onset to treatment day (P =.003), time from admission to treatment day (P
      <.001), time to maximal radiographic score from treatment day (P =.001), maximal
      radiographic score (P =.009), Sao2 at maximal radiographic score (P =.13), and
      treatment radiographic score (P =.03). Fair responders had shorter time between
      admission and treatment than did either good (P <.001) or poor responders (P
      =.002) and shorter time between symptoms and treatment (P <.001) and lower
      treatment radiographic score (P =.012) than did good responders. Good (82%), poor
      (36%), and fair (33%) responders developed maximal chest radiographic scores
      within 4 days of treatment (P =.008). Radiographic patterns at both admission and
      maximal radiographic score did not influence treatment response. CONCLUSION:
      There are significant relationships among radiographic parameters, oxygen
      supplementation, and treatment response, and these relationships appear to be
      clinically useful in the treatment of SARS.

PMID- 14595151
TI  - Beta-thalassemia major: thin-section CT features and correlation with pulmonary
      function and iron overload.
AB  - PURPOSE: To describe and quantify thin-section computed tomographic (CT) features
      of the lung in patients with beta-thalassemia major (beta-TM) and determine the
      correlation between thin-section CT findings, pulmonary function test (PFT)
      results, and iron overload. MATERIALS AND METHODS: Forty-one patients with beta
      TM (mean age, 24.5 years) underwent thin-section CT (during full inspiration and
      expiration) and PFTs. Two radiologists in consensus recorded the presence of
      focal bronchial and parenchymal abnormalities and air trapping. A
      semiquantitative air trapping score (ATS) was used, and patients were separated
      into air trapping-negative (ATS between 0 and 3) and air trapping-positive (ATS >
      3) groups for statistical analysis. Iron overload was estimated by calculating
      the ratio of the signal intensity (SI) of the liver to the SI of paraspinous
      muscle by using magnetic resonance imaging in 27 patients (66%). We performed
      multiple logistic regression analysis to study the influence of age, PFT
      findings, and SI ratio on the presence of air trapping at CT and multivariate
      regression analysis to study the simultaneous influence of the presence of air
      trapping on obstructive PFT indexes. RESULTS: Air trapping was the predominant
      thin-section CT finding and was seen in 10 (24%) of 41 patients. No patient had
      interstitial lung disease at CT, although 11 (27%) had a restrictive spirometric
      pattern. Simple logistic regression analysis revealed significant associations
      between ATS and forced expiratory volume in the first second (FEV1), FEV1/forced
      vital capacity (FVC), forced expiratory flow (FEF) in the midexpiratory phase
      (FEF25%-75%), FEF at 50% of the FVC (FEF50%), and FEF at 75% of the FVC (FEF75%)
      (P =.019,.030,.007,.034, and.021, respectively) but not between ATS and SI ratio.
      At multiple logistic regression analysis, only FEF25%-75% was significantly
      associated with ATS (P =.019, adjusted odds ratio = 0.86, R2 = 41.8%).
      Multivariate analysis revealed that ATS did not have a significant influence on
      lung function indexes (P =.104), although significant effects were found with
      FEV1, FEF25%-75%, FEF50%, and FEF75% when examined separately. CONCLUSION: Air
      trapping may be present at expiratory thin-section CT in patients with beta-TM
      and is associated with reduced FEF25%-75% values but not hepatic iron overload.

PMID- 14595152
TI  - Evaluation of proscriptive health care policy implementation in screening
      mammography.
AB  - PURPOSE: To evaluate the potential effect of proscriptive health care policies
      directed toward improving screening mammogram interpretation in the United
      States. MATERIALS AND METHODS: Percentiles of accuracy based on a random sample
      of 110 U.S. radiologists were used to examine the number of radiologists who
      would need to be restricted from providing mammographic interpretation to
      increase median accuracy from 66% to 67%, 71%, and 76%. In addition, reading
      volume data recorded for the sampled readers were used to project the percentage
      reduction in service volume (mammograms per year) that would result from
      restriction. Characteristics of participating radiologists were compared with
      those of nonparticipating radiologists by using chi2 testing and analysis of
      variance to assess the external validity of the results. RESULTS: To increase
      median accuracy by 1% (from 66% to 67%) would require prohibiting about 2,200
      U.S. radiologists (ie, the 11% in the lowest quantile for accuracy) from
      performing mammographic interpretation and would result in a reduction of yearly
      service volume of approximately 10%. An increase in median accuracy of 5% (to
      71%) would require prohibiting about 6,000 U.S. radiologists (ie, 30%) from
      performing this service, with an accompanying volume reduction of 25%. An
      increase in median accuracy of 10% (to 77%) would require prohibiting about
      11,400 practicing U.S. radiologists (ie, 57%) from performing this service and
      would diminish the national service capacity by 50%. CONCLUSION: These data show
      that implementation of proscriptive health care policies based on accuracy would
      diminish the service capacity of screening mammography in the United States.

PMID- 14595153
TI  - Clip or marker migration 5-10 weeks after stereotactic 11-gauge vacuum-assisted
      breast biopsy: report of two cases.
AB  - Two women, aged 50 and 51 years, underwent stereotactic, 11-gauge vacuum-assisted
      biopsy from the cranial approach of small lesions in the upper outer quadrant of
      the right breast with removal of lesions that were detected with mammography.
      Postbiopsy mammograms showed the metal clip or marker at the biopsy sites in both
      patients. Histologic analysis of both lesions indicated atypical hyperplasia.
      Mammograms obtained prior to surgical excision showed caudal z-axis migration of
      the clip or marker to be 6.5 cm at 5 weeks and 4.5 cm at 10 weeks, respectively.
      By ignoring the clip or marker that had migrated to an inaccurate location and by
      using internal and external breast landmarks to guide presurgical excision needle
      localization, the biopsy sites were successfully excised in both patients.

PMID- 14595154
TI  - Chronic lithium nephropathy: MR imaging for diagnosis.
AB  - PURPOSE: To evaluate the appearance of lithium nephropathy at magnetic resonance
      (MR) imaging. MATERIALS AND METHODS: Sixteen patients with renal insufficiency
      and clinical and laboratory evidence of nephropathy secondary to therapy with
      lithium salts were examined with a 1.5-T MR imaging unit with T1-weighted, T2
      weighted fast imaging with steady-state precession (true FISP), rapid acquisition
      with relaxation enhancement, half-Fourier turbo spin-echo, and gadolinium
      enhanced (FISP three-dimensional MR angiographic) sequences. Renal size and the
      presence, number, location and size of parenchymal cysts were analyzed. The cysts
      in each kidney were defined as rare (fewer than 10 cysts), sparse (between 10 and
      30 cysts), abundant (30-60 cysts), or very abundant (more than 60 cysts).
      RESULTS: The mean length of both kidneys was 104 mm +/- 9 in seven cases, and one
      or both kidneys were less than 90 mm in length in nine cases. Renal microcysts
      measuring from 1 to 2 mm were detected in all patients. They were either very
      abundant (n = 12), abundant (n = 2), or sparse (n = 2). The cysts were located
      with equal abundance in both the cortex and the medulla in 11 cases and were
      predominantly located in the renal cortex in five cases. No renal artery stenosis
      was present. CONCLUSION: Microcysts secondary to long-term lithium therapy can be
      detected with MR imaging.

PMID- 14595155
TI  - Percutaneous vertebroplasty in metastatic disease: transpedicular access and
      treatment of lysed pedicles--initial experience.
AB  - For the treatment of lytic disease involving the pedicles of vertebrae in
      patients with metastatic disease, the authors performed percutaneous
      vertebroplasty by using an access route via the lysed pedicle. Fifty-one pedicles
      were treated in 32 consecutive patients. In all cases, a radiologically
      satisfactory filling of both the affected pedicle and the vertebral body was
      achieved. Clinically effective pain relief was obtained in 24 (75%) of 32
      patients, and no clinical complications were observed.

PMID- 14595156
TI  - Randomized controlled trials and cancer screening.

PMID- 14595157
TI  - The superficial femoral vein.

PMID- 14595158
TI  - Biomechanical explanation of adjacent fractures following vertebroplasty.

PMID- 14595159
TI  - Proper handling of research with invalid conclusions.

PMID- 14595160
TI  - Augmentation of rabbit posterolateral spondylodesis using a novel demineralized
      bone matrix-hyaluronan putty.
AB  - STUDY DESIGN: Posterolateral spinal fusion with allogeneic demineralized bone
      graft-hyaluronan putty in addition to autogenous iliac crest bone graft in a
      rabbit model. OBJECTIVES: To determine the potential efficacy of demineralized
      bone graft-hyaluronan putty as a bone graft enhancer. SUMMARY OF BACKGROUND DATA:
      Autograft bone is the material of choice for posterolateral lumbar
      intertransverse process fusion. Bone graft alternatives such as demineralized
      bone matrices that can be used as graft extenders, enhancers, or substitutes
      continue to be developed. METHODS: One hundred New Zealand white rabbits
      underwent bilateral posterolateral spinal fusion with autogenous iliac crest bone
      graft or bone graft with allogeneic rabbit demineralized bone graft-hyaluronan
      putty. The rabbits were killed 9 weeks later, and the lumbar spines were removed.
      Manual manipulation and fine detail radiography were used to assess spinal
      fusion, and computed tomographic images were used to quantify the volume of the
      fusion mass. RESULTS: In comparison with autograft bone alone, the fusion rates
      were greater when demineralized bone graft-hyaluronan putty was used as an
      adjunct to autogenous bone. Furthermore, the radiographic fusion rate was greater
      when demineralized bone graft-hyaluronan putty was used in a 2:1 ratio to
      autograft bone in comparison with a 1:1 ratio (P = 0.001). The addition of
      demineralized bone graft-hyaluronan putty to autograft bone was found to increase
      mineralized bone volume in a ratio-dependent manner (P < 0.05). CONCLUSIONS:
      Allogeneic demineralized bone matrix-hyaluronan putty enhances rabbit
      posterolateral spine fusion when used as an adjunct to autogenous bone graft.
      This new formulation of demineralized bone matrix may facilitate greater bone
      formation and successful fusion.

PMID- 14595161
TI  - The accuracy of computed tomography in assessing cervical pedicle screw
      placement.
AB  - STUDY DESIGN: A blinded, prospective comparison of computed tomography scan
      accuracy for determining the location of cervical pedicle screw position in human
      cadavers. OBJECTIVES: To establish recommended computed tomography technique
      guidelines for assessing location of cervical pedicle screws. SUMMARY OF
      BACKGROUND DATA: A small number of studies have described the accuracy of
      roentgenography regarding the assessment of pedicle screw position. However, a
      few studies have investigated the accuracy of computed tomography in this
      respect. Ebraheim et al evaluated the relation of lateral mass screws to the
      nerve roots within the intervertebral foramen on oblique radiographs. No study
      has been undertaken, to our knowledge, to specifically define the reliability and
      validity of computed tomography scans in the case of cervical pedicle screw
      placement. METHODS: As a pilot study, 10 cadaveric cervical spines from another
      study with bilateral 3.5 mm titanium pedicle screws were scanned with 1.0 mm
      axial slices. After the scans were interpreted by three blinded readers, each
      panel member was "trained" with regard to individual accuracy. Ten more cadaveric
      cervical spines were instrumented with 3.5 mm titanium screws in each pedicle (C2
      C7). The specimens were then scanned with a variety of computed tomography
      techniques, including spiral acquisitions at 1.0 mm, 1.0 mm + reconstruction, 2.5
      mm, 5.0 mm slices, and the three-dimensional Stealth Station recipes. The
      specimens were dissected, and malpositioned screws were recorded and photographed
      by independent raters. The same three readers from the pilot study then read each
      new scan in random order. RESULTS: Reader accuracies in the pretraining pilot
      study were 74%, 68%, and 52%, with kappa coefficients of 0.49, 0.37, and 0.07,
      respectively, and significant intrarater variances (P = 0.014). After training,
      the accuracy rate improved significantly to 89%, 88%, and 85% in posttraining
      study, and the kappa coefficients were 0.81, 0.78, and 0.73, respectively. Kappa
      statistical analysis showed negligible interreader variance on the entire pivotal
      study except by the three-dimensional Stealth Station format. The overall mean
      kappa coefficients were 0.77, 0.75, and 0.73. Assessment of pedicle screw
      position was statistically inferior with 5.0 mm axial slices, in contrast to
      slices <3.0 mm. CONCLUSIONS: We demonstrated that reliance on computed tomography
      scan data in determining the misplacement of a pedicle screw is usually accurate
      given proper scan acquisition, presentation windows, and adequate reader
      training, but a clinically significant error rate remains. A conventional
      computed tomography scan should not be treated as a gold standard, particularly
      without regard to the readers' training.

PMID- 14595162
TI  - C5 palsy after decompression surgery for cervical myelopathy: review of the
      literature.
AB  - STUDY DESIGN: A literature review was conducted to integrate and compile
      available reports on postoperative C5 palsy. OBJECTIVES: To review the clinical
      features, possible pathogenesis, and procedures for treatment and prevention of
      postoperative C5 palsy as a complication of surgery for cervical compression
      myelopathy. SUMMARY OF BACKGROUND DATA: Although postoperative C5 palsy develops
      in approximately 5% of patients after decompression surgery of the cervical
      spine, its pathogenesis and the options for prevention and treatment remain
      unidentified and many controversies exist. METHOD: We reviewed and analyzed
      papers published from 1986 to 2002 regarding C5 palsy as a postoperative
      complication. Statistical comparisons were made when appropriate. RESULTS:
      Postoperative C5 palsy is reported to occur in an average of 4.6% of patients
      after surgery for cervical compression myelopathy. No significant differences
      were noted between patients undergoing anterior decompression and fusion and
      laminoplasty, nor were distinctions apparent between unilateral hinge
      laminoplasty and French-door laminoplasty, or between cervical spondylotic
      myelopathy and ossification of the posterior longitudinal ligament. Two theories
      were put forth to account for the pathogenesis of C5 palsy: nerve root injury and
      segmental spinal cord disorder. Neither of these hypotheses has been consistently
      supported and evidence to refute each hypothesis can be found in the literature.
      Recently, surgeons have advocated foraminotomy combined with laminoplasty to
      prevent or treat C5 palsy, but further studies into the efficacy of this
      procedure are needed. Although patients with C5 palsy generally have a good
      prognosis for neurologic and functional recovery, those with severe paralysis
      require significantly longer recovery times when compared to more mild cases.
      CONCLUSION: The incidence of postoperative C5 palsy has been reported at 4.6%
      after surgery for cervical compression myelopathy and this value has not varied
      with different surgical procedures or disease etiologies. The pathogenesis of
      postoperative C5 palsy remains unclear at the present time. Patients with
      postoperative C5 palsy generally have a good prognosis for functional recovery,
      but the severely paralyzed cases required significantly longer recovery times
      than the mild cases.

PMID- 14595163
TI  - Cantilever bending technique for treatment of large and rigid scoliosis.
AB  - STUDY DESIGN: Retrospective review of a consecutive clinical series. OBJECTIVES:
      To assess the efficacy and clinical value of cantilever bending technique as a
      technique for correcting large (> or =70 degrees ) and rigid (flexibility < or
      =30%) scoliosis. SUMMARY OF BACKGROUND DATA: Scoliosis correction by current
      methods is a compromise between the rigidity of the deformity and corrective
      forces provided by these methods. For large and rigid scoliosis, the rigidity of
      the deformity cannot be overcome enough to achieve satisfactory correction. Thus,
      anterior release procedures are usually necessary to make the curves more
      flexible and thus improve correction. The cantilever bending technique provides
      powerful corrective forces for overcoming the rigidity of the deformity and
      obviates the need for anterior release procedures. The utility and efficacy of
      the method alone without anterior release for treating large and rigid deformity
      has not been demonstrated. METHODS: A total of 41 consecutive patients undergoing
      cantilever bending technique for the management of large and rigid scoliosis of
      any etiology (congenital, idiopathic, or neuromuscular) were included.
      Radiographic studies, complications, and satisfaction assessment using the
      modified Scoliosis Research Society Instrument were used to assess outcomes.
      RESULTS: The mean Cobb angle of the major curves was 98 degrees (range 75-133
      degrees ). The deformity correction was 67.1% (range 51-74%). Coronal imbalance
      was 2.5 cm before and 0.8 cm after surgery. No major complication occurred.
      Satisfactory correction was achieved in all patients and without anterior release
      in all but one patient. Regardless of the etiology of their deformities, all
      patients were very satisfied with their outcomes. CONCLUSIONS: The cantilever
      bending technique is an effective procedure for the management of large and rigid
      scoliosis regardless of etiology. The clinical value of the procedure was
      demonstrated by reduced need for anterior release, fewer complications, and high
      rates of patient satisfaction.

PMID- 14595164
TI  - Functional and radiographic outcome of thoracolumbar and lumbar burst fractures
      managed by closed orthopaedic reduction and casting.
AB  - STUDY DESIGN: Retrospective review. OBJECTIVES: To determine clinical and
      radiographic outcomes of thoracolumbar and lumbar burst fractures without
      neurologic injury treated by closed reduction and casting. Patient factors
      associated with poor outcome are identified. SUMMARY OF BACKGROUND DATA: The
      results of ambulatory bracing, surgery, and prolonged recumbency for burst
      fractures have been reported. There are no reports of results of closed reduction
      and casting. METHODS: Retrospective review of 41 neurologically intact patients
      with thoracolumbar and lumbar burst fractures was performed. Four patients with
      neurologic injury who refused surgery were included, for a total of 45 patients.
      All patients had closed reduction and casting. Functional, pain, and employment
      status were assessed using the Denis system. Neurologic function was graded using
      the Frankel scale. Radiographic evaluation of vertebral kyphosis, regional
      kyphosis, anterior body compression, and sagittal index were performed at time of
      injury, postreduction, 4 months, and final follow-up. RESULTS: Sixty-four percent
      of patients had minimal or no pain. Eight percent had constant, severe pain. At
      time of injury, 71% of patients were employed. At 8-month follow-up, 58% of
      patients were employed. Closed reduction resulted in significant correction of
      vertebral wedging from a mean of 15 degrees to 5 degrees. Deformity tended to
      recur by 4 months, but the degree of residual deformity appears to be less than
      that reported in other series. No complications resulted from the fracture
      reduction procedure. CONCLUSIONS: Closed reduction and casting of thoracolumbar
      and lumbar burst fractures is a safe treatment method that yields acceptable
      functional and radiographic results.

PMID- 14595165
TI  - Comparison of four tests of quadriceps strength in L3 or L4 radiculopathies.
AB  - STUDY DESIGN: This prospective cohort study evaluated four office tests of
      quadriceps strength in symptomatic adults with radiographic evidence of L3 or L4
      nerve root compression. OBJECTIVE: The study observed the performance of each
      test for its ability to detect quadriceps weakness when compared to the
      asymptomatic side. To determine the potential influence of radicular pain on the
      performance of the four tests, a control group of patients over the age of 40
      with clinical and radiographic L5 or S1 radiculopathies underwent identical
      testing of quadriceps strength. SUMMARY OF BACKGROUND DATA: The L3 and L4 nerve
      roots innervate the quadriceps; therefore, quadriceps weakness may be a
      consequence of L3 or L4 radiculopathies. There are no standardized or validated
      methods to evaluate quadriceps strength in the clinical office setting. This may
      lead to inconsistent detection by clinicians of quadriceps weakness in cases of
      L3 or L4 radiculopathy. METHODS: Thirty-three consecutive patients with L3 or L4
      radiculopathies and 19 with L5 or S1 radiculopathies were studied. The four tests
      of quadriceps strength included: 1) single leg sit-to-stand test; 2) step-up
      test; 3) knee-flexed manual muscle testing; and 4) knee-extended manual muscle
      testing. Results from a second examiner repeating the four tests were used to
      calculate interrater reliability. RESULTS: In L3 and L4 radiculopathies,
      unilateral quadriceps weakness was detected by the single leg sit-to-stand test
      in 61%, by knee-flexed manual muscle testing in 42%, by step-up test in 27% and
      by knee-extended manual muscle testing in 9% of patients. The sit-to-stand test
      detected weakness in all but one case when weakness was detected by another test.
      All patients with L5 or S1 radiculopathies could perform the sit-to-stand test.
      Kappa coefficient was high for sit-to-stand test (0.85), step-up (0.83), and knee
      flexed manual muscle testing (0.66), and low for knee-extended manual muscle
      testing (0.08). CONCLUSION: In L3 and L4 radiculopathies, unilateral quadriceps
      weakness was best detected by a single leg sit-to-stand test. Patients of similar
      age with radicular pain caused by L5 or S1 radiculopathies could perform this
      test. As the interrater reliability of the single leg sit-to-stand test is high,
      clinicians should consider utilizing this test for assessing quadriceps strength
      in cases of L3 and L4 radiculopathies.

PMID- 14595166
TI  - The effect of leg length discrepancy on spinal motion during gait: three
      dimensional analysis in healthy volunteers.
AB  - STUDY DESIGN: This study focused on the effects of leg length discrepancy on the
      motion of the normal spine during gait in healthy male volunteers who wore a heel
      raising orthotic device on the right foot. OBJECTIVE: To evaluate the effect of
      leg length discrepancy on the changes in curvature of the normal spine during
      gait. SUMMARY OF BACKGROUND DATA: There are few published data on the effects of
      leg length discrepancy on the motion of the normal spine during gait. METHODS: An
      orthotic device that raised the heel by 3 cm was used to simulate leg length
      discrepancy. Twenty-two healthy male volunteers participated (age: 28.2 +/- 6.1
      years, average +/- SD). The dynamic curvatures of the spine under two conditions
      (without and with a heel-raising orthotic device; normal gait and heel-raising
      gait) were evaluated during gait. The leg length discrepancy values without and
      with the device were measured and analyzed using a VICON system (Oxford Metrics,
      United Kingdom). RESULTS: The spine showed an asymmetrical lateral-bending motion
      during heel-raising gait as compensation for the leg length discrepancy. Maximum
      lateral bending angle of the thoracic spine was 4.2 +/- 1.4 degrees in heel
      raising gait, whereas it was 3.0 +/- 1.0 degrees in normal gait. Maximum lateral
      bending angle of the lumbar spine was 8.1 +/- 2.8 degrees in heel-raising gait,
      whereas it was 6.1 +/- 2.1 degrees in normal gait. The maximum bending angle and
      bending velocity were significantly larger in the heel-raising gait than in
      normal gait. CONCLUSION: Patients who have leg length discrepancy due to
      disorders in the lower extremities are at greater risk of developing disabling
      spinal disorders due to exaggerated degenerative change. Therefore, treatment for
      leg length discrepancy may be helpful in preventing degenerative spinal changes.

PMID- 14595167
TI  - Correlation of patient satisfaction with symptom severity and walking ability
      after surgical treatment for degenerative lumbar spinal stenosis.
AB  - STUDY DESIGN: Prospective follow-up of 83 patients who had decompressive
      laminotomy with or without fusion for degenerative lumbar spinal stenosis between
      September 1992 and September 1998. OBJECTIVE: To evaluate the significance of the
      correlation between patient satisfaction and both the severity of postoperative
      symptoms and walking ability. SUMMARY OF BACKGROUND DATA: In clinical studies of
      surgery for degenerative lumbar spinal stenosis, patient satisfaction often is an
      item in the outcome questionnaire. However, little is known about the
      relationship of patient satisfaction to postoperative symptoms or functioning.
      METHODS: Patients completed standardized preoperative and follow-up
      questionnaires about symptom severity, walking ability, and their satisfaction
      with the results of surgical treatment. The significance of the correlation of
      patient satisfaction with the severity of postoperative symptoms and walking
      ability was evaluated. RESULTS: The mean length of follow-up was 39 months (range
      12-84 months). The final questionnaire of a series was answered by 77 patients
      (93% of the cohort). By univariate analysis, the correlations of patient
      satisfaction with postoperative back pain, leg pain, numbness, subjective
      difficulty in walking, and walking ability were statistically significant
      (Spearman rank-order correlation coefficient: 0.58, 0.57, 0.53, 0.64, and 0.43,
      respectively). Postoperative walking ability was a weaker correlate of patient
      satisfaction than the severity of postoperative symptoms. By multivariate
      regression analysis, the only independent correlate was subjective difficulty in
      walking. CONCLUSIONS: In the evaluation of patient satisfaction as an outcome in
      patients operated on for degenerative lumbar spinal stenosis, we should keep in
      mind that postoperative functioning is a weak correlate of satisfaction.

PMID- 14595168
TI  - Aprotinin reduces blood loss during spinal surgery in children.
AB  - STUDY DESIGN: A prospective blinded, randomized controlled study compared the
      effect of a perioperative infusion of aprotinin versus placebo during long
      segment spinal fusions in children. OBJECTIVES: To determine whether aprotinin
      decreases blood loss and transfusion requirements in pediatric patients with
      spinal deformities undergoing posterior spinal fusions of seven or greater
      segments. SUMMARY OF BACKGROUND DATA: Blood loss is a major cause of morbidity
      during long segment spinal fusion. Several preoperative and intraoperative
      techniques are currently used to reduce blood loss and transfusion requirements.
      Aprotinin, an antifibrinolytic and anti-inflammatory agent, has been used to
      decrease blood loss in cardiac surgical patients. We designed a prospective,
      randomized, and blinded controlled study to evaluate aprotinin's efficacy in
      reducing bleeding during pediatric spine surgery. METHODS: After obtaining
      informed written consent, we studied 44 children and adolescents who were
      anticipated to be at higher risk for major blood loss during posterior spinal
      fusion. Children were randomly assigned to receive high dose aprotinin or placebo
      infusion during the perioperative period. Patients were assessed for blood loss,
      transfusion requirements, days in the intensive care unit, and days in hospital.
      RESULTS: Demographics in the two groups of patients were similar. The study
      demonstrated a significant reduction in estimated blood loss (aprotinin 545 cc,
      placebo 930 cc) and transfusion requirements (aprotinin 1.1 U, placebo 2.2 U).
      The duration of intensive care unit admission was similar in the two groups, as
      was the time until discharge. CONCLUSIONS: This randomized, blinded study
      suggests that aprotinin significantly decreased blood loss and transfusion
      requirements in pediatric and adolescent scoliosis surgical patients at increased
      risk for intraoperative bleeding.

PMID- 14595169
TI  - Re: Hurwitz EL, Morgenstern H, Harber P, et al. A randomized trial of medical
      care with and without physical therapy and chiropractic care with and without
      physical modalities for patients with low back pain: 6-month follow-up outcomes
      from the UCLA low back pain study. Spine 2002; 27:2193-204.

PMID- 14595170
TI  - Zebris versus Myrin: a comparative study between a three-dimensional ultrasound
      movement analysis and an inclinometer/compass method: intradevice reliability,
      concurrent validity, intertester comparison, intratester reliability, and
      intraindividual variability.
AB  - STUDY DESIGN: Experimental study. OBJECTIVES: To compare two devices for
      measuring cervical range of motion, a three-dimensional ultrasound motion device
      (Zebris) and a gravity-reference goniometer (Myrin). SUMMARY OF BACKGROUND DATA:
      Assessment of cervical range of motion is used to evaluate the effect of
      different treatments, determine impairment, and ascertain the relationship
      between neck disorders and cervical spine mobility. METHODS: Sixty "neck-healthy"
      volunteers (25 men, 35 women; mean age 38 years, range 22-58 years) performed
      active maximal movements in flexion-extension, rotation, and lateral flexion.
      Maximal cervical range of motion was recorded simultaneously with the Zebris and
      Myrin devices. Intradevice reliability, concurrent validity, intertester
      comparison, intratester reliability, and intraindividual variability were
      computed. RESULTS: Our study showed good agreement of full-cycle cervical range
      of motion measurement between devices, testers, and the test and retest
      (intraclass correlation [ICC] was >0.90 for intradevice reliability, >0.93 for
      concurrent validity, and >0.92 for intratester reliability). Method error,
      assessed with the within-subject coefficient of variation for 95% of the
      measurements, was 5.4% to 11.1% for intradevice reliability, 4.4% to 7.6% for
      concurrent validity, 3.6% to 7.6% for intratester reliability, and 5.3% to 9.9%
      for individual variability. Individual variability did not increase with an
      increased cervical range of motion. CONCLUSION: Both devices are reliable and
      showed good agreement. We conclude that the two techniques can be used
      interchangeably. Our study supports the continued use of the Myrin-a gravity
      reference goniometer in routine clinical orthopedic work. The more sophisticated
      three-dimensional method adds information and allows evaluation of combined
      motion in two and three dimensions and is suitable for research.

PMID- 14595171
TI  - Adolescent idiopathic scoliosis: case report with 63-year follow-up postsurgery.
AB  - STUDY DESIGN: Retrospective case report. PURPOSE: To provide true outcome
      analysis by a 63-year follow-up. MATERIAL AND METHODS: A 16-year-old girl had a
      posterior spine fusion for adolescent idiopathic scoliosis in 1939 and has been
      followed ever since. Both original photographs and radiographs as well as current
      material are available. BACKGROUND INFORMATION: A follow-up of this duration has
      not previously been reported. RESULTS: She had a solid T9-L3 arthrodesis and had
      no problems until age 50 when degenerative changes at L3-L4 required extension of
      the fusion to L4. When seen in 2002 at age 79, she had problems with degenerative
      disc disease at L4-S1 with spinal stenosis symptoms. CONCLUSIONS: The original
      fusion area remained solid and without symptoms for 63 years. Distal degenerative
      changes began 34 years after her original surgery and are still present at the 63
      year follow-up. These degenerative changes at L4-L5 and L5-S1 are often thought
      to be secondary to the arthrodesis to L4, but because they are extremely common
      in persons of this age who do not have scoliosis or a fusion mass to L4, it is
      not possible to imply a cause and effect relationship. True outcome results
      cannot be ascertained at a 2-year or even 10-year follow-up.

PMID- 14595172
TI  - An atypical presentation of Langerhans cell histiocytosis of the cervical spine
      in a child.
AB  - STUDY DESIGN: A case report of a child with Langerhans cell histiocytosis of the
      posterior elements of the cervical spine treated conservatively and with long
      term follow-up is described. OBJECTIVES: To describe the unique diagnostic and
      therapeutic challenges of treating Langerhans cell histiocytosis located
      atypically in the posterior elements of the spine. SUMMARY OF BACKGROUND DATA:
      Langerhans cell histiocytosis involves the spine in approximately 20% of children
      with the disease. In nearly 95% of cases, spinal Langerhans cell histiocytosis
      results in destruction of the vertebral body, sparing the posterior elements.
      Confident diagnosis of vertebral body lesions is often made based on plain
      radiographs and MRI; however, the diagnosis of posterior element disease is not
      so straight forward. The natural history of isolated skeletal Langerhans cell
      histiocytosis is benign in most cases. METHODS: The clinical and radiographic
      presentation of a child with Langerhans cell histiocytosis involving the
      posterior elements of C3 is described. A soft tissue mass was observed on
      magnetic resonance imaging; however, a biopsy confirmed the benign diagnosis of
      Langerhans cell histiocytosis. No further surgical treatment was needed, and
      conservative therapy incorporating a short course of cervical bracing and low
      grade chemotherapy was begun. RESULTS: Within a year, reconstitution of the
      posterior elements of C3 was apparent on radiographs. By 9 years after diagnosis,
      the child had near full reconstitution of the posterior elements of C3 and
      resolution of anterior pseudosubluxation of C3 on C4 that was present at
      diagnosis. Although diagnosis of Langerhans cell histiocytosis was made difficult
      by an atypical location in the posterior elements of the spine, after biopsy,
      conservative treatment led to excellent vertebral reconstitution. CONCLUSIONS:
      Isolated involvement of the posterior spine in Langerhans cell histiocytosis has
      not been described in detail previously. The reported case illustrates the
      diagnostic challenges of isolated posterior spine Langerhans cell histiocytosis.
      Despite an unusual presentation, posterior spine Langerhans cell histiocytosis
      should be treated conservatively in a similar manner to anterior lesions.

PMID- 14595173
TI  - Development of lumbar high intensity zone on axial loaded magnetic resonance
      imaging.
AB  - STUDY DESIGN: Case report. OBJECTIVES: To report the development of high
      intensity zones in the lumbar posterior anulus on axial loaded magnetic resonance
      imaging. SUMMARY OF BACKGROUND DATA: The high intensity zone is seen in the
      posterior anulus of degenerate lumbar discs on T2-weighted magnetic resonance
      images and represents a radial anular tear. Although the specificity of the high
      intensity zone for a concordantly painful anular tear in patients undergoing
      discography for discogenic low back pain is high, the sensitivity of magnetic
      resonance imaging for identification of discographically demonstrated anular
      tears is approximately 30%. METHODS: A 55-year-old female with chronic low back
      pain was imaged with lumbar spine magnetic resonance imaging before and following
      axial loading with an magnetic resonance imaging-compatible compression device.
      RESULTS: The nonloaded study demonstrated degeneration of the lower four lumbar
      discs. Following axial loading, posterior central high intensity zones were
      identified at the L2-L3 and L4-L5 levels. CONCLUSION: High intensity zones
      developed on axial loaded magnetic resonance imaging of the lumbar spine. We
      postulate that lumbar spine magnetic resonance imaging with axial loading may
      increase the sensitivity of magnetic resonance imaging for the detection of high
      intensity zones.

PMID- 14595175
TI  - Single versus multiple dose antibiotic prophylaxis in lumbar disc surgery.
AB  - STUDY DESIGN: Retrospective review. OBJECTIVES: To determine the efficacy of
      preoperative antibiotics alone in preventing wound infections following lumbar
      diskectomy. SUMMARY OF BACKGROUND DATA: It is well documented that antibiotics
      given perioperatively reduce the rate of postoperative wound infections in lumbar
      disc surgery. At our institution, the current protocol for patients undergoing
      lumbar diskectomy is a single preoperative antibiotic dose. This study was
      conducted to compare the rate of postoperative wound infection incurred for
      single versus multiple perioperative antibiotic doses. It was hypothesized that
      no significant difference in infection rates would be identified. METHODS: This
      retrospective chart review compared the rates of postoperative wound infections
      incurred when single versus multiple perioperative antibiotic doses were given to
      patients having lumbar laminotomy for herniated discs. The procedures were
      performed between 1993 and March 1999. There were 434 patients in the multiple
      dose group and 201 in the single dose group. The multiple dose group received one
      preoperative and at least three postoperative doses of antibiotics. The single
      dose group received one preoperative dose of antibiotics. A postoperative
      infection was deemed present by either clinical diagnosis or culture results. The
      medical records were reviewed for 6 weeks after surgery for all patients.
      RESULTS: There were 5 out of 435 (1.15%) infections in the multiple dose group
      and 3 out of 201 (1.49%) in the single dose group. Statistical analysis showed no
      significant difference between the two study groups. CONCLUSION: These results
      support the use of single preoperative dose of antibiotics in lumbar disc
      surgery. This is relevant as many lumbar diskectomy patients are candidates for
      early hospital discharge. At our institution, no increased risk of infection
      occurred for the single dose group.

PMID- 14595176
TI  - Circumferential mesh in abdominal wall reconstruction: indications, technical
      notes and case report.
AB  - The authors describe an original technique of abdominoplasty aiming at correcting
      ventral muscles, hypotonia, and relaxation, especially in formerly obese
      patients, pluriparae women, and patients with neuromuscular impairment. The
      technique encloses regular dermolipectomy, laparocele or hernia reduction (if
      existing), ventral fascia plication on the midline, and suprafascial application
      of a purposely built polypropylene mesh. The mesh consists of three continouos
      segments: two lateral, wider, rectangular segments to be fixed on the ventral
      area and one central and narrower (like a belt) segment to be inserted
      posteriorly into the deep subcutaneous tissue above the dorsal muscles and the
      spine. The vehicle of inserting circumferential mesh includes introducing a
      smooth, hollow rod through a small lateral skin access. Then, the two lateral
      segments are extended and criss-crossed over the abdominal muscles and are fixed
      to the iliac periosteum. This allows the dorsal and ventral muscles to be
      contained and supported by the mesh during prolonged standing and exercise.

PMID- 14595177
TI  - Quality analysis of bilateral reduction mammaplasty using a state-legislated
      comparative database and an internal hospital-based system.
AB  - This study analyzed trends in reduction mammaplasty at our institution using
      Atlas and Lastword databases for calendar years 1991 to 1998 and 1993 to 1998,
      respectively. Cases were identified by ICD-9-CM principle procedure codes.
      Patients were analyzed for length of stay (LOS), discharge disposition,
      complications, and readmission. Readmissions to the hospital within 120 days were
      analyzed. Of 705 patients, 628 patients had LOS more than 24 hours, and 77
      patients had LOS less than 24 hours. There was no difference in case-severity
      analysis in any of the 8 years. There was a significant reduction in average LOS
      from 2 to 1.1 days over the 8 years (p < 0.001). There was a significant increase
      per year in number of patients with LOS less than 24 hours (p < 0.002). There was
      no significant difference in readmission rates between patients with LOS less
      than 24 hours and LOS more than 24 hours. Reduction mammaplasty is a high-volume,
      relatively safe, plastic surgical procedure. There was no relationship between
      LOS and complications or readmissions.

PMID- 14595178
TI  - Vascular compromise of the pectoralis major musculocutaneous flap in head and
      neck reconstruction.
AB  - In head and neck reconstructive surgery, the pectoralis major musculocutaneous
      flap is a major reconstructive tool, both in primary as well as secondary
      reconstructions. In a few cases the authors have been able to demonstrate that
      when the pectoralis major musculocutaneous flap is translocated to the mouth
      through a noncompromised neck tunnel, as is done for head and neck
      reconstructions, the taut lateral pectoral nerve is seen to compress the vascular
      pedicle of the flap, adversely affecting its vascularity, which can lead to
      partial or total necrosis of the flap. The authors explain this feature, very
      specific to this flap, with the help of a prospective series of patients.

PMID- 14595179
TI  - Vaginal reconstruction using a modified rectus abdominis musculocutaneous flap in
      pelvic cancer surgery.
AB  - The authors present a modification of the design for the classic cutaneous
      pattern of the rectus abdominis musculocutaneous flap for vaginal reconstruction
      after pelvic cancer surgery. The authors designed a paramedial and supraumbilical
      dermo-cutaneous flap with paraumbilical randomized vascularization, which was
      sutured to the classic cutaneous TRAM flap pattern and rotated around a
      longitudinal axis to form the neo-introitus. The use of this new cutaneous design
      allows for a perfect cylindrical shape all along the length of the new vagina,
      thus achieving a more anatomic reconstruction than those currently obtained with
      the classic cutaneous patterns, and with fewer tendencies to distal retraction,
      necrosis, and partial stenosis.

PMID- 14595180
TI  - The medial circumflex femoral (gracilis) local perforator flap--a local medial
      groin perforator flap.
AB  - The medial circumflex femoral(GRACILIS) perforator free flap has been previously
      used to capture the superior medial thigh skin territory. This can also be
      valuable as a local flap, especially for adjacent groin wounds that are not
      uncommon after vascular interventions. Uncomplicated healing without vascular
      compromise was achieved using this as a local flap in 4 recent cases. Because the
      gracilis muscular branches can be independently dissected from the
      musculocutaneous perforators, the muscle itself can be separately included to
      form a combined conjoint flap, where the muscle is specifically only used to wrap
      around and protect any exposed vascular structures while the cutaneous component
      simplifies skin wound closure. The axis of rotation of the medial circumflex
      femoral perforator local flap extends throughout the groin region and potentially
      to the lateral thigh. This is an ideal local perforator flap because the source
      pedicle has a consistent location already well known to most plastic surgeons,
      the boundaries of the potential skin territory are reliable and well defined, and
      the scar from closure of the donor site within the medial groin can be readily
      concealed by clothing.

PMID- 14595181
TI  - Implantable baclofen pump as an adjuvant in treatment of pressure sores.
AB  - Currently, the success of ulcer treatment is limited by the high recurrence and
      complication rates. Spasticity is an important contributing factor to ulcer
      recurrence, and intrathecal baclofen is an effective method to reduce spasticity.
      Spasticity creates friction, shear, and mobility impairment resulting in wound
      dehiscence, flap loss, infection, and hematoma. Spasticity can be managed
      pharmacologically and surgically; baclofen is the drug of choice. Baclofen
      inhibits spasticity by blocking excitatory neurotransmitters in the spinal dorsal
      horn. Intrathecal baclofen maximizes the dose delivered to spinal receptors and
      minimizes the side effects associated with oral baclofen. Case reports of
      intrathecal baclofen used in patients with pressure sores demonstrate the use of
      intrathecal baclofen to improve reconstructive outcomes in spastic patients.

PMID- 14595182
TI  - Oral burn contractures in children.
AB  - Oral burn contractures in children present major reconstructive problem. Only few
      reports in literature discussed oral burns in children. Electrical, chemical, and
      thermal agents are the main causative agents for oral burns. Oral contractures
      can be classified into anterior, posterior, and total. Anterior contractures are
      usually caused by electrical burns and involve the oral commissure, lips,
      anterior buccal sulcus and surrounding mucosa, and anterior tongue. Posterior
      oral contractures are caused by caustic ingestion and involve the posterior
      buccal mucosa, posterior tongue, retro-molar area and oro-pharynx. Total oral
      contractures involve the lips, tongue, oral cavity, and oro-pharyngeal mucosa and
      are caused by lye caustic ingestion. This report reviews three children; one with
      posterior, two with total oral cavity contracture. All cases were managed by
      linear release of scar contracture and skin grafting followed by a prolonged
      intra-oral splinting with a fixed mouth-block and commissural splint. A
      successful outcome was observed in all cases.

PMID- 14595183
TI  - Randomized, double-blind trial of dolasetron versus droperidol for prophylaxis of
      postoperative nausea and vomiting in patients undergoing TRAM flap breast
      reconstruction surgery.
AB  - Clinical observation indicates that patients undergoing transverse rectus
      abdominus musculocutaneous (TRAM) flap breast reconstruction surgery frequently
      experience postoperative nausea and/or vomiting (PONV). No controlled trials have
      evaluated the role of pharmacologic prophylaxis of PONV in this population. A
      prospective randomized, double-blinded, active-controlled trial comparing
      intraoperative intravenous droperidol 1 mg with dolasetron 50 mg was conducted.
      Seventy-one patients were included in the intention-to-treat analysis. The
      incidence of the primary end point of PONV within 24 hours after surgery was
      81.8% versus 78.9% for droperidol and dolasetron, respectively (p = 0.8). No
      significant differences were detected in the time to onset of PONV, incidence of
      severe nausea or emesis, or incidence of emesis alone. Time to rescue antiemetic
      use was longer in the droperidol group (7.1 vs. 1.3 hours, p = 0.002). Adverse
      effects were similar between the two groups. No PONV-related complications
      occurred during the trial period. The incidence of PONV in TRAM flap breast
      reconstruction surgery patients remains high despite prophylactic intraoperative
      antiemetic administration.

PMID- 14595184
TI  - The effect of hyperbaric oxygen on ischemia-reperfusion injury: an experimental
      study in a rat musculocutaneous flap.
AB  - The effect of hyperbaric oxygen is known to increase survival of ischemic tissue
      but its mechanism is not fully understood. The purpose of this study was to
      evaluate the effect of hyperbaric oxygen on a rat musculocutaneous flap versus
      ischemia-reperfusion injury, focusing on the mechanism involving the expression
      of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) of
      endothelial cells and CD18 of neutrophils. A transverse rectus abdominis
      musculocutaneous (TRAM) flap (6 x 5 cm) supplied by a single superior epigastric
      vascular pedicle was elevated in 100 Sprague-Dawley rats. The rats were divided
      into 4 groups: group 0, sham (n = 10); group I, 4 hours of ischemia followed by
      reperfusion (n = 30); group II, 4 hours of ischemia and hyperbaric oxygen (100%
      oxygen, 2.5 atm absolute, during the last 90 minutes of ischemia before
      reperfusion) followed by reperfusion (n = 30); and group III, 4 hours of ischemia
      followed by reperfusion and hyperbaric oxygen (100% oxygen, 2.5 atm absolute,
      after reperfusion for 90 minutes; n = 30). The study consisted of gross
      examination for flap survival, histology, immunohistochemical staining,
      myeloperoxidase assay, flow cytometric study of CD18, and Northern blot analysis
      on ICAM-1 messenger ribonucleic acid expression. Gross measurement of the flap
      showed increased survival in groups II and III compared with group I (P < 0.05).
      The leukocytes adherent to the endothelium were counted at 24 hours and on day 5.
      Group I leukocytes were significantly increased compared with groups II and III
      (P < 0.05). The myeloperoxidase assay of TRAM flaps at 24 hours revealed a
      significant increase in group I compared with groups II and III (P < 0.05). The
      expression of CD18 was similar between groups I, II, and III. Immunohistochemical
      staining for ICAM-1 and Northern blot analysis on ICAM-1 messenger ribonucleic
      acid showed decreased expression in groups II and III compared with group I.
      Throughout the analysis, groups II and III did not show any significant
      differences. These results suggests that hyperbaric oxygen reduces the
      accumulation of leukocytes in the TRAM flap, but not enough to prevent adhesion
      of neutrophils on endothelial cells; ischemia-reperfusion injury increases the
      expression of CD18 and ICAM-1 and causes increased adhesion of leukocytes on the
      endothelium; hyperbaric oxygen does not alter the expression of CD18 but
      decreases the expression of ICAM-1; and the point of application for hyperbaric
      oxygen, whether applied before or after reperfusion, did not show any differences
      in outcome. In conclusion, the application of hyperbaric oxygen against ischemia
      reperfusion injury increases flap survival and the beneficial effect may be
      explained by a protective mechanism involving downregulation of ICAM-1 on
      endothelial cells.

PMID- 14595186
TI  - Stabilized autologous fibrin-chondrocyte constructs for cartilage repair in vivo.
AB  - Stabilization of fibrin-chondrocyte constructs with fibrinolytical inhibitors has
      been shown to be a feasible method for the reconstruction of cartilage in vitro.
      In this study, the method was tested in vivo. Autologous cultures were used to
      form stabilized fibrin-chondrocyte constructs that were injected into auricular
      cartilage defects of rabbits. Stabilization was achieved by high doses of
      fibrinolytic inhibitors. Samples were prepared for magnetic resonance imaging,
      histology, and immunohistochemistry after 1, 2, 4, and 6 months. Defects of the
      contralateral ear, which were treated with stabilized fibrin without cells, were
      used for controlled comparisons. In all cell-fibrin samples, cartilage-like
      tissue was present. Immunohistochemistry revealed the presence of collagen II.
      This finding was similar for all observations. In the control samples, only minor
      new cartilage could be detected at the cut edges. The reconstruction of cartilage
      in vivo by injecting fibrin-chondrocyte constructs, stabilized with inhibitors of
      fibrinolysis, is thus possible.

PMID- 14595185
TI  - Porcine small intestinal submucosa as a carrier for skin flap prefabrication.
AB  - The feasibility of porcine small intestinal submucosa (SIS) as a carrier in skin
      flap prefabrication was examined in this study. Thirty-eight rats were randomly
      divided into five groups. The saphenous vascular bundle was used as the vascular
      carrier. In group 1 (n = 8), an arteriovenous fistula was made by anastomosis of
      distal saphenous artery and vein. A SIS patch (1.5 x 2 cm2) was placed underneath
      the vascular bundle. In group 2 (n = 8), the vascular bundle was isolated and
      laid over the SIS patch. The distal saphenous vessels were ligated when the flap
      was raised. In group 3 (n = 8), an arteriovenous fistula was made without SIS
      implant. In group 4 (n = 8), the flap was raised with only the vascular bundle
      with the distal end ligated. After 2 weeks of maturation, the flap was raised
      with only the vascular bundle. In group 5 (n = 6), SIS was implanted and the flap
      including the SIS patch was raised and replaced without the vascular pedicles.
      The survival of the flaps and histology were evaluated at 5 days after flap
      replacement. The results showed that the average survival area in group 1 was 99%
      +/- 3% and the survival area in group 2 was 86% +/- 16%. The mean survival areas
      in group 3 and 4 were 60% +/- 9% and 25% +/- 10%, respectively. No flap survival
      was observed in the group 5. These were significantly lower than in groups 1 and
      2 (p < 0.05, p < 0.01). Histology showed that SIS patch was incorporated into the
      adjacent connective tissue and increased amounts of neovascularization were seen
      between the collagenous sheets and dermis. In conclusion, this study demonstrated
      that porcine SIS can incorporate into the adjacent tissue and induce angiogenesis
      in flap prefabrication. This biomaterial can provide a scaffold for supporting
      and enhancing the survival of vascular prefabricated skin flap.

PMID- 14595187
TI  - Tension-induced reduction in connexin 43 expression in cranial sutures is linked
      to transcriptional regulation by TBX2.
AB  - Cranial sutures produce bone at precisely the right rate and time to maintain
      homeostasis. Connexin 43 (CX43), a protein important for communication in bone,
      is downregulated during cell proliferation and is released from suppression or
      upregulated during differentiation. Our previous studies have shown that binding
      sites for the transcription regulatory protein TBX2 are located in the promoter
      sequence, upstream of the Cx43 gene. We have shown that TBX2 binding suppresses
      Cx43 expression. The current study uses transgenic mice in which the TBX2
      promoter has been spliced upstream of the coding sequence for green fluorescent
      protein (GFP). This study shows upregulation of TBX2 after stretching. RNA from
      stretched and unstretched sutures was used for GeneChip and Western analysis. The
      results show an increase in Tbx2 and a decrease in Cx43 gene and protein
      expression with stretch. Our findings support a model of strain-regulated bone
      formation with feedback inhibition that maintains sutural patency during
      development.

PMID- 14595188
TI  - Distally based abductor hallucis muscle flap: anatomic basis and clinical
      application.
AB  - Although rarely used, the abductor hallucis muscle has its indications in
      coverage of small defects at the medial aspect of the hindfoot as a proximally
      based muscle flap. The authors describe a 69-year-old female patient in whom the
      abductor hallucis muscle was used as a distally based flap to reconstruct a
      defect in the forefoot. An anatomic study was undertaken on two cadaveric feet to
      explore the practicality of the distally based abductor hallucis muscle flap
      before it was applied clinically. The distally based abductor muscle flap
      receives its blood supply from minor and major pedicles in a retrograde fashion
      from both the dorsal arterial network and the deep plantar system, through
      communicating branches with the medial plantar artery distally. Transposition of
      the distally based hallucis flap is only advisable in individuals who have no
      vascular compromise in the lower leg and foot. To the authors' knowledge, this
      modification has not yet been described in the available literature.

PMID- 14595189
TI  - Bilateral frontozygomatic dermoid cysts.
AB  - A unique case of frontozygomatic dermoids in a 4-year-old child is presented. A
      bilateral, synchronous presentation in this location has not been reported
      previously in the literature. Both lesions were excised concurrently through
      upper eyelid crease incisions. The etiology, natural history, management, and
      prognosis of dermoids are reviewed.

PMID- 14595190
TI  - Correction of atrophic nasal ala by sandwiching an auricular cartilage graft
      between para-alar and nasal floor retrogressive flaps.
AB  - To correct atrophy of the nasal ala, combined flaps of the para-ala and the nasal
      floor were used. The flaps were pedicled on the alar base then slid in a
      retrograde fashion. Auricular cartilage harvested from the concha was placed in
      the original ala and between the para-alar and the nasal floor flaps to support
      the reconstructed nasal ala. The resulting skin defects in the nasal floor were
      covered with the skin grafts taken from postauricular regions. Postoperative
      scars were not conspicuous because suture lines were placed on the alar groove
      and the postauricular groove.

PMID- 14595191
TI  - A cutaneous manifestation of antiphospholipid antibody syndrome.
AB  - Antiphospholipid antibody syndrome is a disease defined by the presence of a
      hypercoagulable clinical state in association with antiphospholipid antibodies.
      This syndrome can involve large-vessel thrombosis or thrombotic microangiopathy.
      Approximately 40% of patients will present with a cutaneous manifestation as the
      first indication of this disease, with a marked number of patients concurrently
      developing multiorgan involvement. The authors present a patient with extensive
      cutaneous necrosis-a devastating sequela of antiphospholipid antibody syndrome.
      Additionally, multiorgan involvement developed, requiring systemic
      anticoagulation and supportive care. When medically stable, plastic surgical
      intervention was necessary to treat extensive areas of cutaneous necrosis.
      Widespread cutaneous necrosis is a rare but known sequela of this syndrome.
      Studies have demonstrated that prophylaxis for thrombosis is not effective.
      However, long-term medical management with oral anticoagulants has been shown to
      reduce the risk of recurrent thrombosis. Occasionally, plastic surgical
      intervention is needed to treat the sequelae of this disease. Therefore,
      knowledge of the presentation and manifestations of this disease is critical in
      the early detection and prompt treatment of patients to prevent life-threatening
      consequences of this catastrophic disease process.

PMID- 14595192
TI  - Risky business.

PMID- 14595193
TI  - Re: ball lightning injuries.

PMID- 14595194
TI  - Re: osteosynthesis in digital replantation using bioabsorbable rods.

PMID- 14595195
TI  - Orbital reconstruction after exenteration with the whole transorbital temporalis
      muscle flap.

PMID- 14595196
TI  - Response to Pan et al., microarray gene analysis and expression profiles of
      Dupuytren's contracture.

PMID- 14595197
TI  - Re: green mountain surgeons.

PMID- 14595198
TI  - Re: green mountain surgeons.

PMID- 14595200
TI  - Assessment and initial treatment of lacerations, mammalian bites, and insect
      stings.
AB  - Millions of wounds are seen in emergency rooms across the United States each
      year. The goals of wound care for all ages are to avoid infection and achieve an
      esthetically pleasing and functional scar. This article reviews the care needs
      associated with acute traumatic wounds. Information presented includes anatomy
      and physiology of skin and wound healing, and assessment and care of lacerations,
      bites, and sting wounds.

PMID- 14595201
TI  - Pressure ulcer prevention and management: the current evidence for care.
AB  - Pressure ulcers, a common occurrence across healthcare settings, are a costly
      phenomenon. Since the publication of the AHCPR Guidelines on Pressure Ulcer
      Prevention and Treatment in the 1990s, additional attention has been focused on
      pressure ulcer prevention and management. This article discusses current evidence
      regarding known causes of pressure ulcers, pressure ucler prevention, pressure
      ulcer classification and assessment, and interventions to effectively manage
      pressure ulcers.

PMID- 14595202
TI  - Wound care of the pediatric burn patient.
AB  - Pediatric burn care requires an extensive knowledge of the pathophysiology of
      burns. Critical to a positive patient outcome is the correlation of burn size and
      depth with appropriate fluid administration, respiratory management, nutritional
      support, and wound care. Due to the nature of the injury where patients' recovery
      times are lengthy, consideration of the child's psychosocial needs must also be
      part of the total plan of care.

PMID- 14595203
TI  - Assessment and management of patients with venous, arterial, and
      diabetic/neuropathic lower extremity wounds.
AB  - Most healthcare providers recognize that management of lower extremity wounds
      presents a difficult challenge. These chronic wounds significantly impact the
      quality of life for individuals and have implications for costs and utilization
      of healthcare resources. Lower extremity wounds can be due to a myriad of
      different diseases, but the primary causes are chronic venous insufficiency,
      lower extremity arterial disease, and diabetes/neuropathy. Differential
      assessment is necessary prior to implementation of management strategies in order
      to address the etiology and pathogenesis factors that are related to each type of
      leg wound. This article presents an overview of the risk and predisposing factors
      for venous, arterial, and diabetic/neuropathic wounds. Additionally, it addresses
      issues of differential assessment including typical locations, common clinical
      characteristics, typical wound appearance, key management issues, considerations
      for alternative treatments, collaborative care, and patient/family education.

PMID- 14595204
TI  - Role of Vernix caseosa in the neonate: potential application in the adult
      population.
AB  - Vernix caseosa is a naturally occurring fetal barrier film produced in late
      pregnancy as a result of sebaceous and epidermal lipids combined with
      desquamation of maturing fetal corneocytes. Vernix lacks desmosomal
      interconnections between corneocytes as demonstrated in adult stratum corneum and
      is, therefore, referred to as a "mobile phase" stratum corneum. Vernix is
      proposed to have multiple fetal/newborn overlapping biological functions:
      moisturization, anti-infective, antioxidant, wound healing, and waterproofing.
      Patients with altered skin integrity due to burn injuries lack the protective
      qualities necessary for wound healing. Emerging research suggests that Vernix
      applied to skin cultures may enhance wound healing. Application of the
      fetal/neonatal skin science findings to the adult burn population offers the
      potential for a clinically relevant homologous substitute for impaired tissue
      integrity.

PMID- 14595206
TI  - Family partnership intervention: a guide for a family approach to care of
      patients with heart failure.
AB  - While family focused care is recommended in standards of care for heart failure
      (HF), little data exist to guide the structure, content, and delivery of family
      care. The purpose of this article is to describe what is known about the impact
      of HF, and to examine a family based approach to improve self-management and
      adherence in HF. A scientific and theoretical background was used to formulate a
      family based approach to HF care, the Family Partnership Intervention (FPI), and
      to determine the feasibility and acceptability of the intervention to family
      members and HF patients. The components of the intervention are described as well
      as examples of how it was used. Lessons learned in implementing the intervention
      during a pilot study are addressed.

PMID- 14595207
TI  - Sleep disturbance symptoms in patients with heart failure.
AB  - Sleep disturbances have a major impact on physical functioning, emotional well
      being, and quality of life, but are not well described in patients with heart
      failure (HF). Eighty-four HF patients completed a sleep survey and provided
      demographic and clinical data. Seventy percent of the patients were male with a
      mean age of 54 years and a mean left ventricular ejection fraction of 22%. Forty
      seven patients (56%) reported trouble sleeping and one-third used sleeping
      medication. The most frequently reported problems were inability to sleep flat
      (51%), restless sleep (44%), trouble falling asleep (40%), and awakening early
      (39%). Using logistic regression, physiological variables were tested as
      predictors of sleep disturbance. Severity of HF, age, gender, etiology, obesity,
      smoking, and use of beta-blockers were not predictors of sleep disturbance. HF
      patients experience significant sleep disturbances, which are not predicted by
      severity of symptoms or clinical status. Problems with sleep are an important
      component of a clinical assessment in this vulnerable population.

PMID- 14595208
TI  - Left ventricular assist devices as destination therapy.
AB  - Although an estimated 16,500 Americans annually could benefit from a heart
      transplant, in 1999 only 2184 heart transplants were performed in the United
      States. These statistics emphasize the severity of the shortage of available
      hearts for transplantation. Circulatory support provided by an implantable Left
      Ventricular Assist Device (LVAD) that meets Food and Drug Administration approval
      as destination therapy is a promising alternative that impacts patient survival.
      As medical technology creates smaller implantable battery-powered circulatory
      assist devices that allow patients to safely live independently in the community,
      nursing's role must change in response. Long-term LVAD patients require
      strategic, anticipatory planning for extended care and emergency preparedness for
      mechanical support. Therefore, practitioners must familiarize themselves with
      these devices as they care for larger numbers of patients with implanted LVADs
      who require assessment and treatment of noncardiac problems during their
      lengthened lifespan.

PMID- 14595209
TI  - Management of decompensated heart failure.
AB  - Much has been written about the management of chronic heart failure (HF) and
      there is strong evidence from many controlled, multicenter trials to support a
      specific strategy for management of compensated HF. There is little evidence and
      limited guidance for the management of patients during a period of
      decompensation. The use of diuretics, inodilators, and vasodilators is based
      primarily on anecdotal observation. This article reviews selected current
      literature in three areas (diuretics, vasodilators, and inotropes) to examine
      objective evidence and expert opinion that are available to guide the advanced
      practitioner who manages the care of patients with decompensated HF.

PMID- 14595210
TI  - Continuous renal replacement therapy for management of overhydration in heart
      failure.
AB  - An estimated 4.8 million Americans are diagnosed with heart failure. Of those, 5%
      to 10% meet criteria for the refractory state of the disease. While therapeutic
      interventions continue to evolve with the changing conceptualization of heart
      failure pathophysiology, overhydration and its deleterious sequelae remain a
      problem for those in the refractory state. The incidence of heart failure
      continues to rise in older individuals. As baby-boomers age across America,
      greater focus on new, more effective therapies must be considered for treatment
      of this disease. Continuous renal replacement therapy (CRRT) is one such
      treatment. The gentle removal of fluid and metabolites while maintaining
      electrolyte balance helps reduce the effects of overhydration in patients with
      heart failure. Increasing use of the therapy in the refractory state of heart
      failure is generating support for early initiation as it continues to demonstrate
      positive effects. Reduction in edema, attenuation of the sympathoadrenal cascade,
      and improved respiratory status have all been documented using the therapy. The
      intent of this article is to provide information for advanced practice nurses and
      direct care providers regarding CRRT for the treatment of heart failure
      refractory to typical therapy.

PMID- 14595211
TI  - The measurement of brain natriuretic peptide in heart failure: precision,
      accuracy, and implications for practice.
AB  - Although advances have been made in the management of heart failure (HF),
      hospital readmission rates remain high. Finding a simple blood test to identify
      HF would dramatically impact the diagnosis and treatment of this syndrome. A
      better understanding of the pathophysiology of HF may result in improved
      treatment measures. Current guidelines do not target any clinical or hemodynamic
      criteria to achieve before discharge. Most efforts to reduce readmissions have
      been focused on drugs, technology, and the use of specialty HF clinics. Brain
      natriuretic peptide (BNP) levels have the potential of providing diagnostic,
      prognostic, and therapeutic information. In addition, BNP levels appear to be
      associated with future cardiac events such as hospital readmission. The purpose
      of this article is to review the precision and accuracy of BNP measurement in
      those with HF, and to describe how measurement of BNP can be used in clinical
      practice. Ultimately, BNP testing may improve the accuracy of the diagnosis of HF
      and guide best treatment practices.

PMID- 14595212
TI  - Brain (B-type) natriuretic peptide: implications for heart failure management.
AB  - Heart failure is the leading cause for hospitalization in the United States,
      resulting in over $8 billion in costs annually. Over 4.8 million Americans are
      afflicted with the disease and the number is increasing as the baby boomer
      generation continues to age. It is imperative that new and innovative modalities
      of therapy and diagnosis evolve as we continue to redefine the nature of heart
      failure and discover more about this debilitating disease. This article addresses
      the implications for endogenous brain (B-type) natriuretic peptide (BNP) testing
      in patients diagnosed with heart failure as well as the implications for the
      first available form of exogenous BNP, nesiritide. In addition, the
      pathophysiology of heart failure and traditional treatment modalities are
      discussed.

PMID- 14595213
TI  - Pattern of gene expression and immune responses to Semenogelin 1 in chronic
      hematologic malignancies.
AB  - Normal testicular-specific proteins are frequently aberrantly expressed by tumor
      cells. Based on this, we have investigated Semenogelin 1, a major protein of
      human semen coagulum thought to be highly specific to seminal vesicles, in
      leukemic cells. Using reverse transcription-polymerase chain reaction,
      Semenogelin 1 gene was frequently expressed in chronic myeloid leukemia (5 of 8,
      62.5%) and chronic lymphocytic leukemia (5 of 12, 41.7%) but rarely in multiple
      myeloma (2 of 30, 6.7%). The gene was not expressed in bone marrow or peripheral
      blood from healthy donors. Semenogelin 1 expression is normally confined to the
      testis, suggesting that it is a novel Cancer-Testis (CT) antigen. Translation of
      the mRNA to Semenogelin 1 protein was confirmed by Western blot analysis of tumor
      cell lysates and by immunocytochemistry. The recombinant Semenogelin 1 protein
      was used with a control Escherichia coli-derived recombinant protein in ELISA and
      Western blot analysis to show that high titer IgG antibodies against Semenogelin
      1 were detected in some patients, suggesting the in vivo immunogenicity of the
      protein. Immune responses predicted gene expression by the leukemia cells.
      Semenogelin 1 was also frequently coexpressed with other CT antigens, Sperm
      protein 17 and SPAN-Xb. These results therefore indicate that Semenogelin 1 is a
      novel CT antigen capable of inducing B-cell responses in vivo in chronic
      leukemias.

PMID- 14595216
TI  - The role of laparoscopy in the chronic pelvic pain patient.

PMID- 14595217
TI  - Pelvic denervation surgery: what the evidence and anatomy teach us.

PMID- 14595214
TI  - NK cells mediate Flt3 ligand-induced protection of dendritic cell precursors in
      vivo from the inhibition by prostate carcinoma in the murine bone marrow
      metastasis model.
AB  - Multiple observations suggest that suppression of the dendritic cell (DC) system
      might be one of the mechanisms used by the tumors to escape immune response.
      However, no in vivo data are available to support these in vitro observations.
      Here we have shown that murine prostate cancer inhibits DC generation
      (dendropoiesis) from the bone marrow precursors in the in vivo model in mice
      injected intrafemorally with RM1 prostate adenocarcinoma cells. Phenotyping of
      DC, generated from in vivo RM1-treated bone marrow cells, revealed a significant
      inhibition of dendropoiesis assessed as a percentage of CD11c+MHCII+,
      CD11c+CD86+, and CD11c+CD80+ cells. The stimulatory capacity of these DCs to
      induce T cell proliferation was also markedly decreased. Notably, Flt3 ligand
      based therapy reversed the inhibitory effects of prostate cancer on dendropoiesis
      in vivo in wild-type and C.B-17 SCID (T and B cell deficient) mice, but not in
      SCID beige (T, B, and NK cell deficient) animals, suggesting a key role of NK
      cells in Flt3 ligand-mediated protection of dendropoiesis from tumor-induced
      inhibition in vivo. Thus, these data demonstrate that prostate cancer inhibits DC
      hematopoietic precursors in vivo in the bone marrow and this effect could be
      abolished by a systemic administration of growth factor Flt3 ligand.

PMID- 14595218
TI  - Screening for musculoskeletal causes of pelvic pain.

PMID- 14595219
TI  - Myofascial pain syndrome of the abdominal wall for the busy clinician.

PMID- 14595221
TI  - Chronic pelvic pain as a form of complex regional pain syndrome.

PMID- 14595220
TI  - Peripheral neuropathies and pelvic pain: diagnosis and management.

PMID- 14595222
TI  - Mental health care providers: resource rather than last resort in patients with
      chronic pelvic pain.

PMID- 14595223
TI  - Interstitial cystitis and chronic pelvic pain: new insights in neuropathology,
      diagnosis, and treatment.

PMID- 14595224
TI  - Endometriosis-related pelvic pain: what is the evidence?

PMID- 14595225
TI  - Pelvic vascular congestion-half a century later.

PMID- 14595227
TI  - Technical advances in ultrasound equipment.

PMID- 14595228
TI  - 3D fetal ultrasonography.

PMID- 14595229
TI  - Magnetic resonance imaging in obstetrics.

PMID- 14595230
TI  - Remote interpretation of ultrasound images.

PMID- 14595231
TI  - Routine ultrasound in pregnancy.

PMID- 14595233
TI  - The genetic sonogram in second trimester down syndrome screening.

PMID- 14595232
TI  - Screening for fetal heart disease with ultrasound.

PMID- 14595234
TI  - Nuchal translucency-based screening.

PMID- 14595235
TI  - Noninvasive diagnosis of fetal anemia.

PMID- 14595236
TI  - Arterial and venous Dopplers in IUGR.

PMID- 14595237
TI  - Ultrasound assessment of the cervix.

PMID- 14595238
TI  - [Thiocyanate and central nervous system maturation of young mice].
AB  - Potassium thiocyanate, given to the drink of pregnant mothers provoked a body
      weight decrease of 14 day-old mice (-18%), without perturbations of cerebrum and
      cerebellum weights. The reduction of pups' body weight could be explained by a
      decrease of plasmatic thyroid hormone levels: FT3 and FT4, (-54; -57%) in youngs
      and (-66; -49%) in their mothers. A defect of thyroid hormone levels, observed in
      young mice, provoked a decrease of cerebrum and cerebellum protein concentrations
      (-15 and -13%) respectively. Modifications of biochemical parameters confirmed
      the histological aspects of hypothyroid mice cerebellum with purkinje cells
      incompletely differentiated. When thiocyanate ion was removed from mothers'
      drink, we have noted in pups a partial return of some biochemical parameters
      (iodine thyroid contents, protein concentrations of cerebrum and cerebellum) and
      of cerebellum histological aspects. While thyroxinemia (FT4) and plasmatic FT3
      levels were completely restored and even exceeded control values, which were
      necessary for central nervous system maturity of young.

PMID- 14595239
TI  - Kallmann's syndrome: skeletal and psychological aspects of late diagnosis.
AB  - We report a case of Kallmann's syndrome (KS) in a previously untreated 30-year
      old Caucasian male, admitted to our Endocrinology Department, presenting with
      hypogonadotropic hypogonadism and hypoosmia, and reporting a history of rickets
      in early childhood and a rapid growth pattern. On admission, his main complaints
      were back-pain and a decreased tolerance to physical exercise. The patient gave
      no family history of hypogonadism or hypoosmia, and his case was assumed to be
      sporadic KS. On physical examination hypogonadism (micropenis, small testes, no
      puberty), hypoosmia and severe scoliosis, kyphosis and chest malformations were
      recorded. No facial hair growth was found nor past voice braking. His skeletal
      proportions were eunuchoidal, no mid-line defects were found. This case of KS was
      identified unusually late. Due to patient's anxiety that his physical appearance
      might change due to therapy, he was referred to a clinical psychologist who
      confirmed the patient's self-perception as a male. The risk of further bone
      malformations, progression of osteoporosis and consecutive pathological fractures
      were the main indications for commencing treatment. Psychological support was
      provided. Six months of treatment with low doses of hCG (500 IU given i.m. twice
      a week) had elevated his testosterone levels but they still remained below the
      lower values of the normal reference range for males. Additional treatment with
      vitamin D and calcium supplementation was continued. A certain improvement of
      bone density score was observed. The patient noted a marked pain relief and he
      willingly complied with the treatment. After six months of therapy hCG dose was
      increased to 2000 IU given twice a week. We conclude that even at such a late
      diagnosis of Kallmann's syndrome in a male who accepts his physical appearance
      and does not wish any treatment in this respect, hormonal therapy is necessary
      and should be introduced to reduce significant risk of osteoporosis and bone
      fractures, and also to offset slowly progressing skeletal malformations which
      result from the lack of epiphyseal fusion.

PMID- 14595240
TI  - [Empty sella turcica revealed by panhypopituitarism disclosed by severe
      hyponatremia].
AB  - A 56-year old multiparious woman taking medication for depression was
      hospitalized for vomiting and abdominal pain. Laboratory tests showed severe
      hyponatremia and led to the diagnosis of panhypotuitarism due to an empty sella
      turcica. We recall the mechanism of hyponatremia in this context and point at the
      importance of endocrine tests in patients with an empty sella turcica.

PMID- 14595241
TI  - [Toxic multinodular goiter].
AB  - OBJECTIVES: We report a series of 70 patients with toxic multinodular goiter
      (TMNG) and analyze results after surgical removal. PATIENTS AND METHODS: Over a
      15-year period, patients underwent thyroid surgery for TMNG. The large majority,
      85.5% were women and mean age was 40 years. All patients had had goiter for more
      than 5 years. Clinical signs of toxicity were present in all patients, 100%
      presented tachycardia and palpitations. Nodules were identified at ultrasound in
      95% of the patients and at scintigraphy in 90%. Serum T4 was elevated in 40
      patients and THS was depressed in all. The chest x-ray revealed a plunging goiter
      in 10 patients. All patients were given medical treatment prior to surgery for
      total thyroidectomy in 15 and subtotal thyroidectomy in 55. There were no deaths.
      Two patients developed hematomas, to suffered injury to the recurrent nerve, and
      five developed acute hypoparathyroidism. Three cases of thyroid carcinoma were
      observed. DISCUSSION: TMNG is an indication for radical treatment, generally
      surgery. Medical treatment is required in preparation for surgery. Total
      thyroidectomy is used increasingly, providing a definitive cure of toxic
      hyperthyroidism and avoiding the risk of recurrence. With increasing surgical
      skill, the risk of recurrent or parathyroid injury is greatly decreased.

PMID- 14595242
TI  - [Investigation, treatment and monitoring of late-onset hypogonadism in males: the
      official guidelines of the International Society for the Study of the Study of
      the Aging Male (ISSAM) with comments].
AB  - There is increasing interest in the subject of hormone changes in the aging male,
      which is likely to become particularly important with the expected growth in the
      population of men over 50. The main concerns at present are androgen decline in
      the aging male (ADAM), or partial androgen deficiency of the aging male (PADAM),
      commonly known as the andropause. Although there have been advances in our
      knowledge of androgen deficiency in the aging male, it is still incomplete,
      sometimes confusing, and some aspects of androgen replacement therapy remain
      controversial. The International Society for the Study of the Aging Male (ISSAM)
      therefore felt it was a good time to review the current situation by publishing a
      series of practical and official guidelines concerning the diagnosis, treatment
      and monitoring of late-onset hypogonadism in males. The aim of this study is to
      present the French translation of these recent international guidelines, and to
      comment on them.

PMID- 14595243
TI  - [Hypopituitarism and antiphospholipid syndrome].
AB  - Endocrine disorders seen in antiphospholipid syndrome are rare. To date, these
      disorders have generally involved Addison's disease. Recently reports have
      appeared of a few cases of primary or secondary hypopituitarism associated with
      primary antiphospholipid syndrome. We report the case of a young female patient
      who presented neuroendocrine symptoms during the postpartum period associated
      with an antiphospholipid syndrome. Hormone assessment showed complete anterior
      hypopituitarism and antiphospholipid antibodies were positive. We discuss the
      clinical, biological and radiological features observed in our patient and
      compare results with cases reported in the literature. This case illustrates the
      importance of screening for antiphospholipid syndrome in the etiological work-up
      of hypopituitarism associated with a history of recurrent thrombosis.

PMID- 14595245
TI  - [Fetal intersexuality: management approach].

PMID- 14595244
TI  - [Smoking and the thyroid].
AB  - The effects of smoking on the thyroid gland have been studied for years. The
      consequences of smoking on thyroid function and size are however still
      controversial. It is accepted that an increase in serum thyiocyanate, a potent
      inhibitor of iodine transport, may contribute to the development of thyroid
      dysfunction, particularly in geographical areas with borderline iodine
      deficiency. In the general population, smoking is associated with normal thyroid
      hormone levels, with a tendency to lower TSH levels and enlargement of thyroid
      size. There is an increased risk of developing over thyroid disease. The
      relationship between smoking and relapse of Graves' disease and the incidence and
      severity of Graves' ophthalmopathy are constantly reported. Smoking also has a
      potent nodular goitrigenic effect in low iodine areas. Despite the fact that
      smoking decrease both thyroid secretion and thyroid hormone action,
      hypothyroidism does not appear to be more frequent. Smoking does however increase
      the metabolic effects of hypothyroidism. Active and passive smoking have proven
      deleterious effects on the fetal thyroid. Paradoxically, there is evidence of
      reduced risk for thyroid cancer in smokers.

PMID- 14595246
TI  - [Thyroid and pregnancy].

PMID- 14595247
TI  - [Pregnancy and weight].

PMID- 14595248
TI  - [Effect of gestational diabetes on metabolism].

PMID- 14595250
TI  - [Menopause: towards treatment "a la carte" ].
AB  - In spite of questioning and doubt arising from WHT study hormone substitution
      therapy (HST) has proven efficacy on climacteric symptoms and certain short-term
      and long-term consequences of menopause. Among 1000 women taking HST for ten
      years, eight supplementary cases of breast cancer and 6 fewer cases of colonic
      cancer are observed. No cardiovascular protection has been demonstrated. A
      history of coronary artery disease, vascular disease, stroke or thromboembolism
      are contraindications for HST. The vascular impact of estradiol administered via
      an extra-digestive route in women with a low vascular risk cannot be extrapolated
      from the HERS and WHI trials because these trials were conducted is high-risk
      women, using specific types of steroids given orally. Tibolone has demonstrated
      efficacy and in an alternative to HST after more than one year of menopause. The
      usefulness of phytoestrogens remains to be determined, particularly due to the
      wide individual variability of their effects on climacteric symptoms and the low
      level of proof provided by epidemiological or clinical studies conducted to study
      the prevention of osteoporosis and the risk of breast cancer. Most of the
      analyses present methodological biases. Currently, the most widely accepted
      notion is that there is a beneficial effect on cardiovascular risk. To date,
      SERMs have selective indications and cannot be prescribed for all women:
      raloxifen is used for the prevention and treatment of menopause-related
      osteoporosis. The relative risk of venous thromboembolism with SERMs (raloxifen
      and tamoxifen) is comparable to that observed with HST. HST or any other
      treatment given for menopause must be an individual decision balancing the
      benefits against the risks and taking into account the desires of the patient
      perfectly informed of the currently available evidence. Prescriptions should be
      part of an overall scheme including nutritional advise and physical exercise
      aimed at preserving quality of life and preventing age-related effects which
      largely depend on genetic predisposition and the psycho-affective environment.

PMID- 14595251
TI  - [Medullary cancers of the thyroid: genetic aspects].

PMID- 14595252
TI  - [Hormones and antihormones, cancer of the breast and prostate, escape and
      treatment].

PMID- 14595253
TI  - [New therapeutic approaches in diabetes].

PMID- 14595254
TI  - [Diabetes in the elderly].

PMID- 14595255
TI  - The quality in the radiology department.
AB  - In the last three years, the Spanish juridical ordinance has regulated (mostly
      the radiologic protection area) the essential quality that every radiodiagnostic
      and dentistry unit should comply with. This quality, as in every service, rests
      on the competence of the professional's who perform it. This means that in
      advanced countries much time and effort is dedicated to forming these people and
      therefore the academic charge for teaching dentistry radiology in Venezuela
      results 15 times higher than what is dedicated in our environment. Also, the
      supply of graduates or specialized radiologists is very poor; for example, it
      does not exist in Barcelona while in Merida the radiology service staff has 4
      licentiates exclusively dedicated to oral radiology assistance and teaching
      (apart from two other people who work as technicians). This wealth influences
      positively in the quality of the service. Among other things, it allows the
      readjustment of the incoming petitions and also to justify them better and makes
      possible that all the explorations go out with the corresponding judgment. The
      academic quality in this discipline is also high due to the fact that it is a
      university teaching service. Our goal, through this work, is to show the
      situation of the problem comparing 2 different university services of oral
      radiology and reveal the lacks found with its solutions.

PMID- 14595256
TI  - Biochemical markers of the periodontal ligament.
AB  - For many years the diagnosis of Periodontal Disease has been based on clinical
      and radiographic methods. Other more recent methods have the objective of
      studying the inflammatory response of the host. That way, immunologic and
      biological methods determine the free mediators in the periodontal infection. The
      components of the gingivo-crevicular liquid or fluid are used to identify or to
      diagnose the active disease, to anticipate the risk of acquiring the disease and
      to determine its progress. For it to be clinically useful important changes
      should be registered the way a specific site turns active or that a previously
      disease affected site improves its conditions as a result of periodontal therapy.
      The response of the neutrophillic granulocytes play an important role in the
      detection of Periodontal Disease. The unspecific defense system in the gingivo
      crevicular fluid can be determined through cytokines and/or interleukines that
      serve to identify sites at risk on the patient. In Periodontal Disease, the
      cytokines are not only defense mediators of the gingival sulcus fluid, but are
      also an indicator of tissue destruction. The liberation of high levels of
      lysosomal enzymes by neutrophils, proteolytic enzymes as the collagenases, or
      intercytoplasmatic enzymes as dehydrogenase lactate and aspartate amino
      transferase can equally help monitor the progress of the Periodontal Disease.

PMID- 14595257
TI  - Herpes simplex virus detection in oral mucosa lesions in patients undergoing
      oncologic therapy.
AB  - The presence of Herpes Simplex Virus (HSV) has been a frequent detection in
      gingivitis and ulcerations of oral mucosa in patients undergoing oncologic
      therapy. In these patients, lesions tend to show atypical clinical patterns,
      leading to misdiagnosis. OBJECTIVES: To detect HSV, using an ELISA test, in oral
      lesions of patients under oncologic therapy, to determine localization of these
      lesions in the oral cavity, to relate their presence with the general diagnosis
      of the patient and to compare the test results with the previous clinical
      diagnosis of the lesions. STUDY DESIGN: Thirty lesions where examined in nineteen
      pediatric patients under oncologic therapy. Direct samples of all lesions were
      taken and an ELISA test for HSV type I and II was applied to them. General
      diagnosis of the patients was consigned, as well as localization of the lesions
      in the oral cavity and clinical diagnosis of them. A database was elaborated with
      all the information. RESULTS: 33% of lesions were positive to the test, most of
      them in patients with acute myeloid leukemia. Localization of lesions was not
      restricted to areas of mucosa attached to periosteum, but also in areas like the
      dorsum of the tongue. Positive predictivity of clinical diagnosis was 56,25% and
      negative predictive index was 92,86%. Sensitivity of the test was 90% and
      specificity was 65%. CONCLUSIONS: It is very important to corroborate clinical
      diagnosis of gingivitis and ulcerative lesions of the oral cavity of patients
      under oncologic therapy with laboratory tests, because of the atypical clinical
      presentation that can lead to misdiagnosis.

PMID- 14595258
TI  - Intraoral contact allergy to materials used in dental practice. A critical
      review.
AB  - Intraoral contact allergy reactions are clinically poorly differentiated and
      understood, and are not very commonly described in the specialized literature.
      Although such reactions appear to be scantly relevant, evidence suggests that
      they may be more frequent than previously believed. No single or specific
      clinical picture of intraoral contact allergy exists, though lichenoid reactions
      appear to be the most common manifestations. Epicutaneous patch testing, together
      with the clinical manifestations, constitute the most widely used diagnostic
      approach in such situations. Metals used in dental practice--particularly
      amalgams and gold--are the most commonly reported causes of intraoral allergic
      reactions, though hypersensitivity to resins is increasingly mentioned in the
      literature, as a consequence of their increasingly widespread use. The systematic
      intraoral elimination or substitution of materials inducing cutaneous
      hypersensitivity has recently been questioned, while on the other hand it not
      possible to discard an allergic component in some nonspecific stomatological
      disorders. The present study offers clinicians an evidence-based update of
      current knowledge in this field.

PMID- 14595259
TI  - A practical method for clinical diagnosis of oral mucosal melanomas.
AB  - OBJECTIVE: To present a practical and technically simple method for clinical
      diagnosis of oral melanomas that allows to differentiate this neoplasm from other
      pigmented lesions. PATIENTS AND METHODS: Thirteen oral pigmented lesions with
      suspected diagnosis of mucosal melanomas were submitted to a test named "rubbing
      with a gauze" the surface of the lesion. The test was considered positive when
      the gauze stained dark brown or black due to the presence of melanin-laden cells
      on the epithelial surface. In all cases definite diagnosis was confirmed by
      biopsy. RESULTS: Positive results were obtained in 11 out of 13 cases (84.6%).
      CONCLUSION: Our results establish that the test "rubbing with gauze" the surface
      of oral pigmented lesions demonstrates a high sensitivity to anticipate
      clinically the diagnosis of mucosal melanomas. However, a negative result does
      not exclude this neoplasm, since there are some cases in which malignant cells
      have not invaded the superficial epithelial layers. In every case the final
      diagnosis must be established by histopathologic or immunohistochemical analysis.

PMID- 14595260
TI  - Pre-assessment of severely handicapped patients suitable of dental treatment
      under general anesthesia.
AB  - OBJECTIVE: To analyze the importance of an individualized preoperative assessment
      in severely handicapped patients suitable of dental treatment under general
      anesthesia (GA). DESIGN: The study group consisted of 564 patients referred to a
      Special Needs Unit specialized in the dental care of handicapped people, who
      would be treated under GA. Medical and dental records of every patient were
      evaluated, as well as the findings in the oral examination and the assessment
      carried out by the anesthesiologists. RESULTS: Approximately 15% of patients
      (n=84) did not have any dental needs at the time of the examination; 42% (n=234)
      underwent treatment under GA and 43% (n=242) were treated under local anesthesia.
      Only 1.7% of the patients liable to undergo GA were discharged by the
      anesthesiologist due to their systemic condition. Medical and dental
      complications were scarce and, generally mild. During the follow-up period (mean
      44 +/- 6 months) 4.8% of patients needed another treatment session under GA due
      to new dental pathology. CONCLUSION: Applying systematic selection criteria to
      perform any dental treatment under GA in severely handicapped patients reduces
      the indiscriminate use of this technique, minimizing complications as well as the
      necessity of new interventions.

PMID- 14595261
TI  - Oral manifestations of graft versus host disease. Case report.
AB  - This study has been carried out in order to understand and increase our knowledge
      about the oral manifestations and the treatment required for Graft Versus Host
      Disease. The complication of allogeneic transplants with haematopoietic cells is
      revised. The clinical case report deals with a nine-year-old girl who was treated
      in our unit of Integrated Paediatric Dentistry after referral by her
      paediatrician. The symptoms of Graft Versus Host Disease are basically
      characterised by immunodeficiency, diarrhoea, weight loss, dermatological and
      hepatic alterations and oral manifestations. This group of syndromes, caused by
      the fact that the receptor acquires 30% to 50% of the donor's immune system, can
      become acute leading to a 20% to 30% mortality rate. The syndromes are chronic in
      50% of cases, when sometimes the destruction of the salivary glands is the only
      manifestation and has a mortality rate of 5%. From the odontological point of
      view 80% of patients are affected, although we should make the distinction
      between the manifestations which are directly caused by the disease, and those
      caused by chemotherapy or radiotherapy. Oral manifestations (caries, mucositis,
      ulcers, infections, etc) should be treated as soon as possible. Positive co
      operation between physicians is of vital importance.

PMID- 14595262
TI  - Review of 61 cases of odontoma. Presentation of an erupted complex odontoma.
AB  - Odontomas are benign tumors of odontogenic origin characterized by their slow
      growth. They consist of enamel, dentine, cementum and pulpal tissue and
      constitute 22% of all odontogenic tumors. Two types of odontoma are recognized:
      compound and complex. The first is approximately twice as common as complex
      odontomas. The purpose of this study is to value the prevalence of this kind of
      tumors in the ambulatory-surgical gambit and their clinical symptoms. We want to
      emphasize the exceptional spontaneous eruption of this tumors and we report a
      case of erupted complex odontoma. We made the revision of the cases of diagnosed
      odontomas between 1983 and 2001 in the Clinica Ntra. Sra. del Remei, in the
      Centro Medico Teknon and the Master de Cirugia e Implantologia Bucal of the
      Odontologic Clinic (Barcelona University). We analyzed their prevalence,
      distribution in gender, age of the patients, anatomic location, adjacent
      structures affectation, symptoms, histologic classification and treatment. 52.4%
      of the cases were diagnosed in females. 37.7% of the tumors were complex
      odontomas and 62.3% were diagnosed as compound odontomas. 55.7% of all cases were
      in the maxilla and 44.3% in the mandible. The anterior portion of maxilla was the
      most common location (54% of cases). Only a case (1.6%) was erupted, in the
      molars area of the maxilla.

PMID- 14595264
TI  - [Differential diagnosis of parotid gland swellings and tumors].

PMID- 14595265
TI  - [Management of aphtous stomatitis].

PMID- 14595263
TI  - Expression of ErbB-3 and ErbB-4 protooncogene proteins in oral squamous cell
      carcinoma: a pilot study.
AB  - BACKGROUND: To examine the occurrence of ErbB-3 and ErbB- 4 in oral squamous cell
      carcinoma, as well as investigate statistical correlations between the expression
      of these protooncogene proteins and clinical and pathological tumor
      characteristics. STUDY DESIGN: Nineteen oral squamous cell carcinomas (SCC) were
      analyzed using immunohistochemistry. RESULTS: Positive immunostaining for ErbB-3
      was found in 13/19 (68%) cases and for ErbB-4 in 10/19 (52%). The intensity of
      immunostaining for ErbB-3 positive cases was low in 8 (42.1%) and high in 5
      (26.3%) cases, and for ErbB-4 ones was low in 6 (31.6%) and high in 4 (21%) of
      the 19 cases. ErbB-4 overexpression and TNM stage showed a significant
      correlation (Spearman correlation coefficient=0.467; P=0.04). The Kaplan-Meier
      analysis showed that the overexpression of ErbB-3 and ErbB-4 had no an influence
      on survival (P>0.05), but TNM stage was inversely related to survival (P=0.04).
      There was a significant association between the expression of ErbB-3 and ErbB-4
      (chi2=6.193, P=0.037). CONCLUSION: The results of the present study suggest that
      c-erbB-4 may contribute to tumor growth and progression.

PMID- 14595266
TI  - [Dental management of epilepsy patients].

PMID- 14595267
TI  - Effects of resveratrol on acoustic trauma.
AB  - OBJECTIVE: The purpose of the study is to test the ability of resveratrol to
      protect the auditory system from reactive oxygen species (ROS)-mediated noise
      damage. Oxidative stress is mediated by ROS, which are known to cause cellular
      and molecular damage. Interfering with this process, using ROS
      inhibitors/scavengers such as antioxidants has shown promise in protecting
      specific systems from oxidative damage. Among the antioxidants receiving recent
      attention is resveratrol, an active component in red wine. Study design and
      setting Ten Fischer rats were used for this study. The experimental group (n = 5)
      received 7 weeks of resveratrol treatment (430/microg/kg/day), by gavage, and the
      control group (n = 5) received normal saline solution by gavage. Baseline
      auditory brainstem responses (3, 6, 9, 12 and 18 kHz) were determined for both
      groups. After 21 days, animals were exposed to noise (105 dB, 4500 to 9000 Hz for
      24 hours). Postnoise auditory brainstem responses were assessed at 4 recovery
      time points: immediate, at 3 days, 7 days, and 4 weeks after noise exposure.
      RESULTS: Results demonstrate that the resveratrol group showed reduced threshold
      shifts compared with the control group after noise exposure. These shifts were
      significantly different between groups at 6 and 9 kHz (P < 0.05), corresponding
      to the region most represented by the frequency of the traumatic
      noise.Conclusion/significance Initial studies in our laboratory as well as other
      investigators have shown the importance of specific antioxidant therapy in the
      prevention of ischemic, noise, and age related hearing loss. The current study
      demonstrates a protective effect of resveratrol on noise-induced hearing loss.

PMID- 14595268
TI  - Dose-response relationship of topically applied mitomycin C for the prevention of
      laser myringotomy closure.
AB  - OBJECTIVE: We sought to determine a dose-response curve for topical mitomycin C
      when used to prolong the patency of laser-assisted myringotomies. STUDY DESIGN
      AND SETTING: Bilateral myringotomies were performed using the argon laser in 40
      guinea pigs with normal ears. Pledgets with (0.05, 0.2, 0.4, or 2.0 mg/mL)
      mitomycin C were applied topically. Monitoring consisted of weekly or biweekly
      otomicroscopy. RESULTS: As in previous studies, all saline-treated myringotomies
      closed by day 7. By day 14, all myringotomies (100%) in the 0.05 mg/mL group were
      closed. By contrast, all myringotomies (100%) remained patent in the 0.2 and 0.4
      mg/mL treatment groups, and 56% of the myringotomies remained patent in the 2.0
      mg/mL group at day 14. By day 56, all myringotomies were closed in the 2.0 mg/mL
      group, 5 (50%) myringotomies were patent in the 0.4 mg/mL group, and 1 (11%)
      myringotomy was patent in the 0.2 mg/mL group. The study was terminated on day 84
      (12 weeks). At that time, only the 0.4 mg/mL group had patent myringotomies (n =
      3; 30%). The highest dose (2.0 mg/mL) of mitomycin was significantly associated
      with otorrhea. Otorrhea also appeared to be associated with earlier myringotomy
      closure. CONCLUSION: There is a dose-response curve for topical mitomycin C when
      used for prolonging myringotomy patency in doses up to 0.4 mg/mL. Higher doses do
      not appear to prolong patency and are associated with greater otorrhea,
      suggesting middle ear toxicity.

PMID- 14595269
TI  - Resolution of facial stimulation in otosclerotic cochlear implants.
AB  - OBJECTIVES: We examined the incidence of facial nerve stimulation in a population
      of patients with otosclerosis implanted with the Nucleus 22, Clarion 1.2, or
      Clarion High Focus (CHF) device. STUDY DESIGN AND SETTING: A retrospective chart
      review was used for 147 patients who had been implanted with electronic cochlear
      devices at the University of Minnesota between June 1986 and February 2001.
      Seventy-four patients were implanted with the Nucleus 22, 41 patients were
      implanted with the Clarion 1.2 (without a positioner), and 32 patients were
      implanted with the CHF I or II. RESULTS: Eleven (14.9%) of the 74 patients
      implanted with the Nucleus 22 device had facial stimulation. There were 9
      patients with otosclerosis. Seven (78%) of the 9 patients with otosclerosis had
      facial stimulation. One (2.4%) of the 41 patients implanted with the Clarion 1.2
      device (without a positioner) had facial stimulation and that 1 (100%) patient in
      the group had otosclerosis. There were 4 patients in the CHF group with
      otosclerosis. One patient experienced stimulation, but it was possible to
      decrease maximum current levels and still use the electrode pair. CONCLUSION:
      Facial stimulation appears to be less problematic in patients with otosclerosis
      implanted with the CHF devices.

PMID- 14595270
TI  - Coronal computed tomography prevalence of superior semicircular canal dehiscence.
AB  - OBJECTIVES: The relatively new clinical entity superior canal dehiscence syndrome
      (SCDS) is diagnosed by clinical symptoms and signs. Coronal computed tomography
      (CT) has been used to confirm the diagnosis. A consecutive series of temporal
      bone CT scans was reviewed to define the prevalence of a dehiscent-appearing
      superior semicircular canal. STUDY DESIGN AND SETTING: Temporal bone CT scans
      performed over a 2-year period at a university-based tertiary referral center
      were reviewed independently by 3 individuals. Scans were excluded if coronal
      images were not obtained or reconstructed from axial images. Prevalence figures
      for dehiscent-appearing superior semicircular canal were determined by consensus.
      Medical records of selected individuals with a dehiscent-appearing canal were
      reviewed for study indications and otologic symptoms. RESULTS: A dehiscent
      appearing superior semicircular canal was seen in 9% of studies. Correlation
      among examiners was greater than 94%. Medical records indicated symptoms
      suggestive of or compatible with the diagnosis of SCDS in rare cases. CONCLUSION:
      The prevalence of a dehiscent-appearing superior semicircular canal on coronal CT
      of the temporal bones performed with 1.0-mm collimation is substantially greater
      than that predicted by temporal bone histologic study. Clinical symptoms
      compatible with the diagnosis were seldom recorded, suggesting low specificity.
      The high sensitivity and low specificity of CT scan create a risk for
      overdiagnosis of SCDS if the coronal CT scans are not correlated with clinical
      symptoms.

PMID- 14595271
TI  - Endoscope affects decision making in cholesteatoma surgery.
AB  - OBJECTIVE: The aim of the present study was to evaluate the use of intraoperative
      otoendoscopy as a factor that could influence surgical decision-making in
      cholesteatoma surgery. MATERIALS AND METHODS: The material of this study included
      82 ears with acquired cholesteatoma that were operated on. They were divided into
      4 groups according to the surgical technique chosen and the use of the endoscope.
      Group I included 22 ears that underwent canal wall-down (CWD) tympanomastoid
      surgery, group II included 20 ears that underwent CWD tympanomastoid surgery with
      intraoperative use of endoscopy, group III included 20 ears that underwent canal
      wall-up (CWU) tympanomastoid surgery, and group IV included 20 ears that
      underwent CWU tympanomastoid surgery with intraoperative use of endoscopy.
      Endoscopy was used as a complementary tool to microscopy. The follow-up period
      ranged from 12 to 48 months. RESULTS: Intraoperative remnants of cholesteatoma
      matrix were detected during both CWU and CWD by the use of the rigid endoscope.
      However, its incidence was higher in the CWU group (50%) than in the CWD (30%)
      group. Most of these remnants were in the sinus tympani (37.5%). The mean
      duration of follow-up was 18.19 (+/-8.7) months. Postoperative residual
      cholesteatoma was much higher in the CWU group (25%) than in the CWD group (5%).
      All residuals were from groups of patients in whom intraoperative endoscopy was
      not used in the primary surgery. CONCLUSION: Our results showed that the use of
      the endoscope gave the surgeon better control over the pathology, thus achieving
      better eradication. Stated differently, the use of the endoscope raised the
      surgeon's confidence level about total removal and thus encouraged the surgeon to
      keep the canal wall intact while removing cholesteatoma in hidden areas.
      Therefore, the use of endoscope could be considered an additional tool that may
      affect decision-making in cholesteatoma surgery.

PMID- 14595272
TI  - The agger nasi cell: the key to understanding the anatomy of the frontal recess.
AB  - The key to successful surgery in the frontal recess is a complete understanding
      of the anatomy. The frontal recess is behind the beak of the frontal bone between
      the lamina papyracea and superior portion of the middle turbinate. It is a
      hazardous and complex area with a range of anatomical configurations. This
      article describes the anatomy of the frontal recess as it relates to the agger
      nasi cell using this cell as the key around which the anatomy is built. The
      simplest anatomical configuration is explained first and this knowledge is built
      upon so that the more complex configurations can be better understood. The
      classification of frontal ethmoidal cells by Kuhn is incorporated into the
      anatomical description of the various configurations. The implication of each
      anatomical variation on the surgical approach to the frontal recess is discussed.

PMID- 14595273
TI  - Beta-trace protein test: new guidelines for the reliable diagnosis of
      cerebrospinal fluid fistula.
AB  - OBJECTIVE: Cerebrospinal fluid (CSF) fistulas need to be reliably diagnosed for
      the optimal management. Recently, in preference to beta2-transferrin, another CSF
      protein, beta-trace protein (betaTP), is similarly used with a new method for CSF
      diagnosis. This study evaluates the sensitive interpretation and limits of this
      new betaTP test for use in routine CSF fistula diagnosis. METHODS: Nephelometric
      detection of betaTP has been made in nasal secretion, serum, and CSF samples from
      healthy individuals as well as patients with reduced glomerular filtration rate
      and with bacterial meningitis. Additionally, 53 patients with suspected CSF
      rhinorrhea are also analyzed. RESULTS: The betaTP test can also be used to
      reliably diagnose CSF rhinorrhea even slightly better than the beta2-transferrin
      test. It should not be used for patients with renal insufficiency and bacterial
      meningitis as they substantially increase serum and decrease CSF betaTP values,
      respectively. CONCLUSION: Quantitative measurement of betaTP is a noninvasive,
      highly sensitive, quick, and inexpensive method that can be used for the
      detection of CSF rhinorrhea in nasal secretions. However, in cases where there is
      doubt about the interpretation, the results should be proved with beta2
      transferrin test or sodium-fluorescein test.

PMID- 14595275
TI  - Clinical predictors of long-term success after endoscopic sinus surgery.
AB  - OBJECTIVE: Determining the clinical predictors of long-term success after
      endoscopic sinus surgery (ESS) would better guide the management of patients.
      METHODS: One hundred-thirty chronic rhinosinusitis (CRS) patients were evaluated
      retrospectively. Overall subjective improvement was 83% with a mean follow-up of
      60 months. Eighty percent had anatomic variations; 36.2%, allergy; 55.4%, nasal
      polyps; and 26.9%, history of previous operation. The improvement was 100%, 94%,
      79.5%, and 69.7% in stages 0, I, II, and III, respectively. With other
      parameters, the success rates were 68.1% and 91.6% with and without allergy,
      73.6% and 94.8% with and without polyps, 54.3% and 93.7% with and without
      previous history of surgery, 84.4% and 82.7% with and without anatomic
      variations, and 23.8% and 94.4% with and without recurrent polyps. CONCLUSION: In
      multivariate Cox regression analysis, allergy (P < 0.05; relative risk, 4.6) and
      previous polypectomy (P < 0.05; relative risk, 9.9) were found to be predictors
      of poor prognosis in the long-term follow-up.

PMID- 14595274
TI  - Comparisons of two intranasal corticosteroid preparations in treating allergic
      rhinitis.
AB  - OBJECTIVES: Intranasal corticosteroid preparations can relieve symptoms of
      allergic rhinitis. Different aqueous corticosteroid forms have been developed for
      intranasal use. The objectives of this study were to compare efficacy and safety
      between fluticasone propionate and budesonide in the treatment for patients with
      allergic rhinitis. METHODS: The study was conducted in a prospective and
      randomized manner; a total of 24 adult patients were enrolled. All patients
      received MAST allergen test at entry and again at 2 months after treatments.
      Fourteen patients received fluticasone propionate 200 microg once daily, and 10
      patients received budesonide 200 microg twice daily. To investigate the efficacy
      of fluticasone propionate and budesonide, a subjective scoring system was
      designed to evaluate the symptom improvement of patients. Adverse events were
      recorded on a diary card then were analyzed. Mann-Whitney U test and Kruskal
      Wallis 1-way analysis of variance were used for statistical analysis. RESULTS:
      Analysis on patient-based symptom scores revealed that both fluticasone
      propionate and budesonide were equally efficacious in improving the symptoms of
      nasal blockage, sneezing, nasal itching, and watery rhinorrhea. There were no
      significant side effects reported for both groups during this follow-up period.
      However, analysis showed that the fluticasone propionate group demonstrated
      significantly greater improvement in some MAST allergen tests (Candida, mite,
      house dust; P < 0.05). CONCLUSION: Clinically, fluticasone propionate 200 microg
      once daily was efficacious as budesonide 200 microg twice daily in the relief of
      allergic rhinitis symptoms. However, fluticasone propionate can achieve greater
      immunologic improvement. Both preparations showed no evidence of short-term side
      effects.

PMID- 14595276
TI  - Intracapsular tonsillar reduction (partial tonsillectomy): reviving a historical
      procedure for obstructive sleep disordered breathing in children.
AB  - OBJECTIVE: We sought to reintroduce a historical procedure-intracapsular
      tonsillar reduction (partial tonsillectomy or tonsillotomy)-for tonsillar
      hypertrophy causing obstructive sleep disordered breathing (OSDB) in children, as
      well as to determine whether partial tonsillectomy, compared with conventional
      (total) tonsillectomy when performed by more than one surgeon, is equally
      effective for the relief of OSDB while resulting in less pain and more rapid
      recovery. STUDY DESIGN: We conducted a retrospective case series at a tertiary
      children's hospital. The charts of children who underwent partial tonsillectomy
      and total tonsillectomy (1998 through 2002) for postoperative complications were
      reviewed. The caregivers were surveyed to assess postoperative pain, rapidity of
      recovery, and effectiveness of surgery for relieving symptoms of OSDB. RESULTS:
      Two hundred forty-three children underwent partial tonsillectomy and 107 children
      underwent total tonsillectomy. There were no significant differences in immediate
      and delayed complications between the groups. Both operations were equally
      effective in relieving OSDB. Children who had partial tonsillectomy had
      significantly less postoperative pain and significantly more rapid recovery.
      CONCLUSION: Intracapsular tonsillar reduction with an endoscopic microdebrider
      relieves OSDB as effectively as conventional tonsillectomy, but results in less
      postoperative pain and a more rapid recovery.

PMID- 14595277
TI  - Preliminary findings from a prospective, randomized trial of two tongue-base
      surgeries for sleep-disordered breathing.
AB  - OBJECTIVES: This study compares the efficacy of 2 tongue-base surgical procedures
      in the treatment of patients with moderate to severe sleep-disordered breathing.
      STUDY DESIGN AND SETTING: We conducted a prospective, randomized crossover
      surgical trial at a university hospital. METHODS: Seventeen patients with
      moderate to severe sleep-disordered breathing and Fujita type II upper airway
      collapse for whom conservative treatment failed were enrolled into an
      institutional review board-approved surgical protocol. They were randomly
      assigned to undergo palatopharyngoplasty combined with either tongue advancement
      (mandibular osteotomy) or tongue suspension. Parameters assessed included
      severity of sleep-disordered breathing (polysomnography), sleepiness (Epworth
      Sleepiness Scale), and anatomic changes (upper airway endoscopy), as well as
      demographic factors. Patients not achieving satisfactory improvement in their
      condition were offered nonsurgical management or additional surgical treatment
      that varied based on the postoperative assessment but included crossing over to
      the other tongue surgical procedure. RESULTS: Nine of the 17 patients were
      randomized to the tongue suspension group, and 8 to the tongue advancement group.
      In the 9 tongue suspension patients, Epworth Sleepiness Scale scores fell from
      12.1 to 4.1 (P = 0.007). Airway collapse for all 9 patients measured on Muller
      maneuver improved, by a mean of 64% (P = 0.0006) at the palate and 83% (P =
      0.0003) at the base of the tongue. In the 8 tongue advancement patients, Epworth
      Sleepiness Scale scores fell from a mean of 13.3 to 5.4 (P = 0.004). Airway
      collapse for 5 of 8 patients measured on Muller maneuver improved by a mean of
      31% (P = 0.1) at the palate and 75% (P = 0.03) at the base of the tongue.
      CONCLUSION: Prospective, randomized trials of tongue-base surgery for sleep
      disordered breathing are possible. Preliminary findings from the current protocol
      reveal a slight advantage of tongue suspension over tongue advancement.

PMID- 14595278
TI  - Head and neck reconstruction with anterolateral thigh flap.
AB  - OBJECTIVE: Our goal was to present our experience with the free anterolateral
      thigh flap for reconstruction of various cutaneous and mucosal defects of the
      head and neck. STUDY DESIGN: We conducted a retrospective review of 37 patients
      who underwent reconstruction between 1994 and 2002. Outcome measures included
      ethnicity, flap harvest technique, vascular anatomy, flap success, general
      surgical complications, and donor site morbidity. RESULTS: The majority of our
      patients were white (n = 33). The size of the 39 free anterolateral thigh flaps
      varied from 24 to 252 cm(2). There was 1 arterial failure and flap loss (2.6%)
      and 2 venous occlusions that were both salvaged. The donor site was closed
      primarily in 37 cases and with a split-thickness skin graft in 2 cases.
      CONCLUSIONS: This is the first report on using the free anterolateral thigh flap
      in whites. This free transfer has proved to be a versatile and reliable flap for
      reconstruction of the head and neck.

PMID- 14595279
TI  - Comparing a mechanical device with medicinal leeches for treating venous
      congestion.
AB  - OBJECTIVE: To compare mechanical device therapy to medicinal leech therapy for
      treating venous congestion. STUDY DESIGN: Fasciocutaneous flaps of 9 x 7-cm
      (porcine model, n = 11) were elevated and the associated veins clamped for 15
      hours. Device-treated flaps (n = 6) were treated with up to 3 devices/flap. Leech
      treated flaps (n = 5) were treated with 75 leeches/flap (5 leeches/hour).
      Treatment evaluation parameters included: blood volume removed, skin color,
      surface perfusion, tissue oxygen tension, and endpoint histology. RESULTS: No
      significant differences were seen in blood volume removed, surface perfusion, and
      oxygen tension. However, significant differences were seen in skin color change
      over time. Histological assessment showed mild congestion in 5/5 leech-treated
      flaps and 2/6 device-treated flaps. CONCLUSION: Device therapy was comparable to
      leech therapy for decongesting a 9 x 7-cm flap over a 15-hour period. However,
      digital images and significant differences in skin color change over time
      demonstrate that device therapy promotes more global decongestion versus leech
      therapy.

PMID- 14595281
TI  - Predictors of survival in early oral cancer.
AB  - OBJECTIVE: Despite the substantial rate of neck conversion reported among
      patients with early oral cancer, a policy of routine elective neck dissection has
      been criticized on the grounds that it confers little survival advantage while
      subjecting many to potentially avoidable morbidity. However, the identification
      of factors predictive of survival may allow for the identification of those
      patients who are more likely to benefit from elective neck treatment. STUDY
      DESIGN AND SETTING: The clinical and histologic material of 71 patients with
      stage I or II squamous carcinoma of the oral cavity were reviewed. Patients were
      followed up for a minimum of 3 years after their surgery, and the impact of these
      variables on 3-year survival was assessed. RESULTS: Increased tumor thickness was
      significantly predictive of decreased survival (P = 0.030). Although having no
      prognostic value alone, when combined with thickness, both pattern of invasion
      and gender increased the significance of the latter in predicting outcome.
      Conclusion and significance Measuring tumor thickness and pattern of invasion in
      patients with early oral cancer may allow for the identification of those
      patients with more aggressive disease who are more likely to benefit from
      elective neck treatment.

PMID- 14595280
TI  - Surgical management of amiodarone-induced thyrotoxicosis.
AB  - OBJECTIVE: Amiodarone can cause thyroid dysfunction in patients with or without
      previous thyroid disease. With increased use from its placement in advanced
      cardiac life support guidelines and cardiac transplant programs, the incidence of
      amiodarone-induced thyrotoxicosis (AIT) will likely increase. Medical management
      is complex and nonuniform and frequently fails. This study investigates the role
      of surgery in AIT and proposes indications for surgical management. STUDY DESIGN
      AND SETTING: Two AIT case reports at a tertiary care institution and 31 surgical
      AIT cases in the world literature are reviewed. METHODS: The 2 AIT cases involved
      patients with cardiomyopathy and resistant arrhythmias. Despite medical therapy,
      both patients' conditions failed to improve. Thirty-one surgical cases of AIT in
      the literature are evaluated with respect to symptoms and onset, medical therapy,
      AIT classification, pathology, perioperative management, and complications.
      RESULTS: Both patients underwent total thyroidectomy without difficulty or
      complication, one as an overnight stay and one as an inpatient with an
      intraaortic balloon pump. One patient received a successful cardiac transplant
      and the other remains a viable candidate. In the literature, the majority (80%)
      of surgical cases are AIT type II (less common type) with no underlying thyroid
      disease. Range and duration of symptoms varied, in addition to type and duration
      of medical management. Almost all patients underwent total thyroidectomy, and all
      were successful with no mortality and minimal morbidity. CONCLUSION: AIT can
      develop in any patient during or after amiodarone therapy. Medical management is
      extremely difficult due to the absence of a proven therapeutic armamentarium, and
      surgery offers a safe, viable option. Surgical management should play a larger
      role in treatment algorithms and should be strongly considered for patients whose
      conditions necessitate continuation of amiodarone, or with severe symptoms
      resistant to medical therapy.

PMID- 14595282
TI  - Ketoprofen for postoperative pain after uvulopalatopharyngoplasty and
      tonsillectomy: two-week follow-up study.
AB  - OBJECTIVE: In our previous study, we reported that both uvulopalatopharyngoplasty
      (UPPP) and tonsillectomy are associated with unacceptable intense pain during the
      first 24 hours after surgery. To investigate the pain progression at home, we
      followed the same 53 patients for 14 days after surgery. Twenty-two patients
      underwent tonsillectomy and 31 patients underwent UPPP. STUDY DESIGN: A
      prospective, longitudinal, parallel-group study was conducted. METHODS: Beginning
      on the first postoperative day, the patients were allowed to use 50 mg ketoprofen
      capsules at a dosage of 5 mg/kg/24 hr. The patients evaluated their own pain four
      times a day for the first 5 days. Two weeks after the surgery during a follow-up
      visit patients reported the present pain; and a total consumption of analgesics,
      and all adverse events for 14 days. RESULTS: Patients in both study groups had
      significant pain, especially in the morning, for the first week after surgery. In
      half of the patients, severe pain interfered with eating and sleeping, and in one
      third of the patients, the pain lasted 2 weeks or longer. The need for ketoprofen
      was significantly higher after UPPP than that after tonsillectomy (P = 0.001).
      One patient after tonsillectomy and 3 patients after UPPP needed electrocautery
      to stop secondary bleeding. CONCLUSIONS: Both UPPP and tonsillectomy are
      associated with intense postoperative pain. Standard ketoprofen capsules are too
      short-acting to ensure undisturbed sleep.

PMID- 14595283
TI  - Gastroesophageal reflux disease: symptoms versus pH monitoring results.
AB  - OBJECTIVES: The reason why some patients with gastroesophageal reflux disease
      (GERD) have symptoms of upper aerodigestive system irritation, while others
      mainly have gastroenterologic symptoms, is not well established. This
      retrospective case series study was designed to examine the existence of a
      correlation between symptoms and reflux characteristics, based on data obtained
      from esophageal pH monitoring. METHODS: The study population consisted of 139
      patients; 97 patients presented with laryngopharyngeal symptoms of GERD,
      including unexplained hoarseness, throat clearing, chronic cough, laryngospasm,
      globus, throat pain, and 42 patients presented with gastroenterologic symptoms,
      including heartburn and regurgitation. The results of 24-hour, double-channel
      ambulatory esophageal pH monitoring were analyzed comparing 2 symptom groups. The
      incidence of abnormal acid reflux at the upper and lower esophageal segments and
      the effects of upright and supine positions on reflux parameters were evaluated.
      RESULTS: The incidence of laryngopharyngeal reflux was significantly higher in
      the laryngopharyngeal symptom group than in the other (52% versus 38%). The
      patients with laryngopharyngeal reflux from both groups showed no significant
      differences in terms of number of acid reflux episodes, percentage of times pH
      was 4, and esophageal acid clearance. Upright and supine parameters did not show
      significant differences between the patient groups. Upright acid reflux episodes
      were, however, common in both groups at the lower esophageal and
      laryngopharyngeal segments. CONCLUSION: Recent studies suggesting that
      otolaryngologic patients commonly show upright, daytime reflux with normal
      esophageal clearance and that typical GERD patients commonly have supine,
      nocturnal reflux with prolonged esophageal clearance are not supported by this
      study. This study indicates that acid reflux parameters and positional changes
      are not sufficient to explain why patients with GERD experience different
      symptoms. The regional symptoms of GERD may be attributed to the impairment of
      epithelial resistance, motor activity, and buffering systems for the esophageal
      antireflux barrier.

PMID- 14595284
TI  - Synovial cell sarcoma of the maxillary sinus: a first reported case.

PMID- 14595285
TI  - Steroid psychosis after head and neck surgery: case report and review of the
      literature.

PMID- 14595286
TI  - Angiotensin-converting enzyme inhibitor-induced unilateral tongue angioedema.

PMID- 14595287
TI  - Epithelioid hemangioendothelioma of the parotid gland with atypical features.

PMID- 14595288
TI  - Recalcitrant otorrhea due to Pseudomonas biofilm.

PMID- 14595289
TI  - Transesophageal echocardiography: an unusual case of iatrogenic laryngeal trauma.

PMID- 14595290
TI  - Successful nonoperative therapy for Kaposiform hemangioendothelioma involving the
      neck: report of 1 case.

PMID- 14595291
TI  - Nasal leprosy: case study.

PMID- 14595292
TI  - The role of endoscopy in the evaluation and treatment of patients with
      pancreaticobiliary malignancy.
AB  - This is one of a series of statements discussing the utilization of GI endoscopy
      in common clinical situations. The Standards of Practice Committee of the
      American Society for Gastrointestinal Endoscopy prepared this text. In preparing
      this guideline, a MEDLINE literature search was performed, and additional
      references were obtained from the bibliographies of the identified articles and
      from recommendations of expert consultants. When little or no data exist from
      well-designed prospective trials, emphasis is given to results from large series
      and reports from recognized experts. Guidelines for appropriate utilization of
      endoscopy are based on a critical review of the available data and expert
      consensus. Further controlled clinical studies are needed to clarify aspects of
      this statement, and revision may be necessary as new data appear. Clinical
      consideration may justify a course of action at variance to these
      recommendations.

PMID- 14595294
TI  - Obscure gastrointestinal bleeding.
AB  - This is one of a series of statements discussing the utilization of GI endoscopy
      in common clinical situations. The Standards of Practice Committee of the
      American Society for Gastrointestinal Endoscopy prepared this text. In preparing
      this guideline, a MEDLINE literature search was performed, and additional
      references were obtained from the bibliographies of the identified articles and
      from recommendations of expert consultants. When little or no data exist from
      well-designed prospective trials, emphasis is given to results from large series
      and reports from recognized experts. Guidelines for appropriate utilization of
      endoscopy are based on a critical review of the available data and expert
      consensus. Further controlled clinical studies are needed to clarify aspects of
      this statement, and revision may be necessary as new data appear. Clinical
      consideration may justify a course of action at variance to these
      recommendations.

PMID- 14595296
TI  - Electrosurgical generators: MAY 2003.

PMID- 14595298
TI  - Can symptoms predict endoscopic findings in GERD?
AB  - BACKGROUND: It is difficult to decide which patients with reflux symptoms require
      endoscopy. The aim of this study was to develop a scoring system to predict
      esophageal findings at endoscopy. METHODS: A consecutive sample of 1011 adult
      patients scheduled for upper endoscopy were asked to complete a validated symptom
      questionnaire. The endoscopy reports were abstracted. Individual logistic
      regression models were developed to predict esophagitis, Barrett's esophagus
      (long and short segment) and esophageal stricture, including Schatzki's ring.
      RESULTS: Reflux esophagitis was independently associated with heartburn frequency
      (p<0.0001) but not severity or duration (p>0.05). Barrett's esophagus was
      associated with the duration of acid regurgitation (p<0.005) but not with
      frequency or severity (p>0.05). Strictures were associated with dysphagia
      severity (p<0.0001) and duration (p<0.0001) but not frequency (p>0.05). At a
      sensitivity of 80%, the models had a specificity of 49% for esophagitis, 57% for
      Barrett's esophagus, and 68% for strictures. At a specificity of 80%, the
      sensitivities were 51% for esophagitis, 62% for Barrett's esophagus and 71% for
      strictures. CONCLUSIONS: Endoscopic findings were associated with distinct
      attributes of reflux symptoms. Symptoms are only modestly predictive of findings
      at endoscopy.

PMID- 14595299
TI  - A prospective randomized comparison of curved array and radial echoendoscopy in
      patients with esophageal cancer.
AB  - BACKGROUND: Both curved array and radial scanning echoendoscopy are used for
      locoregional staging of cancer arising in the esophagus or cardia. The accuracy
      of TNM staging of these malignancies by curved array and radial EUS was compared
      in a prospective, randomized study. METHODS: Patients with cancer of the
      esophagus or cardia were examined by both curved array and radial echoendoscopy
      in randomized order by the same endosonographer in an unblinded fashion. The
      staging results and the examination time for the two echoendoscopies were
      compared and statistically analyzed, and finally compared with surgical and
      histopathologic staging. RESULTS: A total of 104 patients underwent EUS; 36 had
      surgical resection of the tumor, 26 surgical exploration without resection, and
      42 did not undergo surgery. Comparison of the TNM staging results for the two
      echoendoscopies gave high kappa values (T, 0.77; N, 0.75; M, 0.89), indicating
      excellent agreement. The accuracy of curved array echoendoscopy and radial
      echoendoscopy by component of the TNM staging system were, respectively, T, 72%
      and 73%; N, 70% and 77%; and M, 61% and 57%. Mean procedure time for the curved
      array and radial examinations was, respectively, 15 and 12 minutes (p<0.01).
      CONCLUSION: There was no clinically relevant difference between curved array and
      radial echoendoscopy in the staging of cancer of the esophagus or cardia. The
      choice of echoendoscope for TNM staging in patients with these malignancies is,
      therefore, a question of personal preference.

PMID- 14595300
TI  - The role of endoscopic Doppler US in patients with peptic ulcer bleeding.
AB  - BACKGROUND: Stigmata of recent hemorrhage are important prognostic signs for
      patients with ulcer bleeding, but these are subjective findings. This study
      evaluated the additional diagnostic value of Doppler US assessment in patients
      with a bleeding peptic ulcer. METHODS: A prospective, multicenter study was
      performed of patients with ulcer bleeding. Stigmata of recent hemorrhage were
      classified according to the Forrest classification, after which the ulcer was
      assessed by using an endoscopic Doppler US system. Patients with a Forrest Ib-IIb
      ulcer with a positive Doppler signal received endoscopic therapy. Patients with a
      Forrest IIc-III ulcer with a positive Doppler signal were allocated randomly to
      endoscopic therapy or no therapy. No ulcer without a Doppler signal was treated.
      RESULTS: A total of 80 patients were enrolled. Of the Forrest Ib-IIb ulcers, 82%
      had a positive Doppler signal. Of the Forrest IIc-III ulcers, 53% had a positive
      Doppler signal. There was no difference in the rates of recurrent bleeding,
      surgery, or mortality between the group with Forrest Ib-IIb ulcers and between
      the Forrest IIc-III group with and without Doppler signal, but there was little
      power in the sample size to detect differences. Bleeding recurred in 3 patients
      without a Doppler signal. Recurrent bleeding was more frequent in the group in
      which a Doppler signal was still present immediately after endoscopic therapy
      (3/11 vs. 1/27; p=0.06). CONCLUSIONS: This study did not substantiate a role for
      endoscopic Doppler US when this was added to the Forrest classification for
      making clinical decisions in patients with ulcer bleeding.

PMID- 14595301
TI  - A prospective trial of variable stiffness pediatric vs. standard instrument
      colonoscopy.
AB  - BACKGROUND: The pediatric variable stiffness colonoscope is believed to have
      theoretical advantages over the standard colonoscope, however a systematic
      evaluation of this instrument in routine clinical practice involving adult
      patients is lacking. METHODS: Consecutive patients (blinded) undergoing
      colonoscopy in an outpatient endoscopy center by one of 4 experienced
      colonoscopists had the procedure performed with a standard colonoscope (n=384) or
      pediatric variable stiffness colonoscope (n=413). Failure to negotiate the
      sigmoid colon within 10 minutes was regarded as a failure and, if suitable, the
      patient was crossed over to colonoscopy with the alternative instrument. RESULTS:
      Median (95% CI) time to the cecum was significantly faster in the pediatric
      variable stiffness colonoscope group (odds ratio 5.0: 95% CI[4.7,5.3] minutes)
      compared with the standard colonoscope group (odds ratio 5.5: 95% CI[5.2,5.8]
      minutes, p=0.01). There were 22 failures overall (2.8%), 14 in the standard
      colonoscope group (3.6%) and 8 in the pediatric variable stiffness colonoscope
      group (1.9%; p=0.1). With regard to the 14 failures in the standard colonoscope
      group, colonoscopy was attempted with the pediatric variable stiffness
      colonoscope in 13 and completed successfully in 12 (92%). The pediatric variable
      stiffness colonoscope was superior in cases of severe stenosing diverticular
      disease; two of 27 examinations with the pediatric variable stiffness colonoscope
      were rated as failed vs. 12 of 18 with the standard colonoscope (p<0.001).
      CONCLUSIONS: Intubation time was faster with the pediatric variable stiffness
      colonoscope, but use of this instrument was not associated with a superior cecal
      intubation rate compared with the standard colonoscope. However, in patients with
      severe stenosing diverticular disease, the intubation rate with the pediatric
      variable stiffness colonoscope was superior.

PMID- 14595302
TI  - Lower frequency of peritoneal carcinomatosis in patients with pancreatic cancer
      diagnosed by EUS-guided FNA vs. percutaneous FNA.
AB  - BACKGROUND: Studies have suggested an increased risk of peritoneal seeding in
      patients with pancreatic cancer diagnosed by percutaneous FNA. EUS-FNA is an
      alternate method of diagnosis. The aim of this study was to compare the frequency
      of peritoneal carcinomatosis as a treatment failure pattern in patients with
      pancreatic cancer diagnosed by EUS-FNA vs. percutaneous FNA. METHODS:
      Retrospective review of patients with non-metastatic pancreatic cancer identified
      46 patients in whom the diagnosis was made by EUS-FNA and 43 with the diagnosis
      established by percutaneous FNA. All had neoadjuvant chemoradiation. Patients
      underwent restaging CT after completion of therapy, followed by attempted
      surgical resection if there was no evidence of disease progression. RESULTS:
      There were no significant differences in tumor characteristics between the two
      study groups. In the EUS-FNA group, one patient had developed peritoneal
      carcinomatosis compared with 7 in the percutaneous FNA group (2.2% vs. 16.3%;
      p<0.025). No patient with a potentially resectable tumor in the EUS-FNA group had
      developed peritoneal carcinomatosis. CONCLUSIONS: Peritoneal carcinomatosis may
      occur more frequently in patients who undergo percutaneous FNA compared with
      those who have EUS-FNA for the diagnosis of pancreatic cancer. A concern for
      peritoneal seeding of pancreatic cancer via percutaneous FNA is warranted. EUS
      guided FNA is recommended as the method of choice for diagnosis in patients with
      potentially resectable pancreatic cancer.

PMID- 14595303
TI  - Are drugs a risk factor of post-ERCP pancreatitis?
AB  - BACKGROUND: Pancreatitis is the most severe complication of ERCP. The aim of this
      study was to assess whether the use of potentially pancreatotoxic drugs is a risk
      factor for post-ERCP pancreatitis. METHODS: Risk factors for post-ERCP
      pancreatitis and all drugs taken during the month before ERCP were recorded
      retrospectively in a database. Patients with other causes of acute pancreatitis
      or chronic pancreatitis were excluded from the analysis. Post-ERCP pancreatitis
      was defined as abdominal pain and/or vomiting associated with amylase/lipase
      plasma levels equal to or greater than twice the upper normal value. RESULTS: A
      total of 173 patients (95 men, 78 women; mean age, 68 [16] years) were included.
      Post-ERCP pancreatitis occurred in 31 patients (18%). Several risk factors were
      identified in a multivariate analysis: difficulty in cannulation (p<0.001),
      endoscopic sphincterotomy (p<0.005), and female gender (p=0.02). Having taken
      potent pancreatotoxic drugs increased the occurrence of post-ERCP pancreatitis:
      odds ratio 3.7: 95% confidence intervals [1.1,12.4], p=0.04. CONCLUSIONS: Use of
      pancreatotoxic drugs before or during ERCP significantly increased the risk of
      post-ERCP pancreatitis. Thus, discontinuation of the use of such drugs before
      ERCP seems justified whenever possible.

PMID- 14595305
TI  - Intraductal papillary mucinous tumors of the pancreas: the preoperative value of
      cytologic and histopathologic diagnosis.
AB  - BACKGROUND: The preoperative diagnosis of intraductal papillary mucinous tumors
      of the pancreas must be as certain as possible because removal of a large portion
      of the pancreas or even total pancreatectomy may be necessary. The value of
      cytologic and histopathologic analysis of specimens obtained by preoperative
      endoscopic investigations is unknown. The aim of this study was to assess the
      value of such analyses of specimens obtained by EUS-guided FNA and/or biopsy, or
      transpapillary biopsy specimens obtained during endoscopic retrograde
      pancreatography for the diagnosis of intraductal papillary mucinous tumors of the
      pancreas and for the detection of malignancy. METHODS: Between 1992 and 2001, 42
      patients (22 men, 20 women; median age 64 years) underwent surgical resection for
      intraductal papillary mucinous tumors of the pancreas and had preoperative
      pancreatic tissue sampling. In the case of isolated dilatation of pancreatic
      ducts, pancreatic juice was obtained by EUS-guided FNA for cytologic analysis. In
      the presence of a solid lesion or main pancreatic duct stenosis, biopsy specimens
      were obtained by EUS-guided FNA biopsy or endoscopic retrograde pancreatography,
      which permitted histopathologic assessment. The accuracy of cytology and
      histopathology was evaluated for the following: (1) positive diagnosis of
      intraductal papillary mucinous tumors of the pancreas and (2) assessment of
      malignancy, by comparison with histopathologic examination of surgical resection
      specimens. RESULTS: Cytologic analysis was performed in 19 patients; it was
      positive in 4 (21%) and noninformative in 15 (79%). Histopathologic analysis was
      performed in 23 patients; it was positive in 21 (91%) and negative in 2 (9%).
      Histopathologic analysis yielded a positive result in 83% of patients who did not
      have extrusion of mucus from a patulous papilla. The sensitivity, specificity,
      and positive and negative predictive values of histopathologic analysis for the
      diagnosis of malignancy were, respectively, 44%, 100%, 100%, and 33%. When
      histopathologic analysis was positive, the tumor grade was similar to that
      determined by final histopathologic examination in 38% of patients, whereas the
      grade was underestimated in 62%. No complication occurred as a result of tissue
      sampling. CONCLUSIONS: The sensitivity of histopathologic analysis of EUS-guided
      FNA biopsy specimens or transpapillary biopsy specimens is 91% for the positive
      diagnosis of intraductal papillary mucinous tumors of the pancreas with a solid
      component, which is of particular interest as extrusion mucus from the papilla
      was absent in most patients. Histopathologic analysis of biopsy specimens of
      malignant intraductal papillary mucinous tumors of the pancreas often
      underestimates tumor grade. The result for cytologic analysis of juice obtained
      from dilated pancreatic ducts is disappointing.

PMID- 14595306
TI  - Endoscopic treatment compared with medical therapy for the prevention of
      recurrent ulcer hemorrhage in patients with adherent clots.
AB  - BACKGROUND: Two recent randomized, controlled trials have demonstrated efficacy
      for combination endoscopic therapy in the management of bleeding peptic ulcer
      with adherent clot. The aim of this study was to determine the effectiveness of
      this technique in a clinical practice setting. METHODS: Medical records of
      consecutive patients, seen from January 1992 through December 1999, with severe
      ulcer hemorrhage and non-bleeding adherent clots resistant to target irrigation
      were reviewed. The decision for combination endoscopic therapy (epinephrine
      injection, removal of adherent clot, treatment of underlying stigmata) or medical
      therapy was left to the discretion of the endoscopist. RESULTS: Of 244 patients
      with adherent clots, 138 (56.6%) had endoscopic therapy and 106 (43.4%) were
      managed with medical therapy alone. The baseline characteristics of the two
      groups were similar, except for older age in the endoscopic therapy group.
      Recurrence of bleeding within 7 days of endoscopy was significantly less frequent
      in the endoscopic therapy group than the medical therapy group (respectively,
      8.7% vs. 27.4%; adjusted odds ratio 0.07 95% CI [0.02, 0.22], p<0.001). Median
      hospital stay (6.0 vs. 8.0 days; p<0.001), median number of red blood cell
      transfusions after endoscopy (2.0 vs. 3.0 units; p=0.01), the need for repeat
      endoscopy (9.4% vs. 26.4%; p<0.001), and recurrent bleeding within 30 days (10.1%
      vs. 28.3%; p<0.001) were significantly lower in the endoscopic therapy group. In
      addition, the need for ulcer surgery (5.8% vs. 9.4%; p=0.28) and 30-day mortality
      (3.6% vs. 7.5%; p=0.18) were lower in the endoscopic therapy group, although
      these differences were not statistically significant. Endoscopic complications
      were uncommon (1.4% vs. 0.9%; p=1.00). CONCLUSIONS: Combination endoscopic
      treatment of ulcers with an adherent clot was associated with a significant
      reduction in recurrent ulcer hemorrhage compared with medical therapy alone.
      These findings confirm that the efficacy of combination endoscopic therapy
      demonstrated in carefully designed, randomized, controlled clinical trials can be
      reproduced when this technique is applied in a clinical practice setting.
      However, combination therapy did not significantly reduce the need for ulcer
      surgery or 30-day mortality.

PMID- 14595307
TI  - Autofluorescence endoscopy for detection of high-grade dysplasia in short-segment
      Barrett's esophagus.
AB  - BACKGROUND: The occurrence of precancerous lesions, such as high-grade dysplasia,
      in patients with short-segment Barrett's esophagus is controversial. This study
      assessed the efficacy of autofluorescence endoscopy for detection of high-grade
      dysplasia in short-segment Barrett's esophagus. METHODS: A total of 34 patients
      (28 men, 6 women; age range 40-77 years) with histopathologically proven short
      segment Barrett's esophagus were studied. Autofluorescence endoscopy was
      performed by using monochromatized blue light (425-455 nm) filtered from a
      conventional xenon light source. A total of 136 and 109 biopsy specimens were
      taken from Barrett's mucosa under control, respectively, white light endoscopy
      and autofluorescence endoscopy. RESULTS: High-grade dysplasia was found in 9
      (8.3%) autofluorescence-guided biopsy specimens, which was significantly greater
      than the number of white light endoscopy-guided biopsy specimens with this
      finding (one positive biopsy specimen, 0.7% of total biopsy specimens obtained).
      Autofluorescence endoscopy detected high-grade dysplasia in 7 patients, 6 more
      than were identified with white light endoscopy. In the one patient with high
      grade dysplasia detected by white light endoscopy-guided biopsy specimens,
      autofluorescence-guided biopsy specimens revealed only low-grade dysplasia.
      CONCLUSION: Autofluorescence endoscopy in patients with short-segment Barrett's
      esophagus increases the detection rate of high-grade dysplasia.

PMID- 14595308
TI  - Use of a colonoscope instead of a sigmoidoscope to screen asymptomatic adults for
      colorectal cancer.
AB  - BACKGROUND: Colonoscopic screening can detect neoplasms in asymptomatic adults,
      many of which would not be detected by sigmoidoscopy. However, because of cost
      and resource factors, many adults still undergo flexible sigmoidoscopy for
      colorectal cancer screening. In asymptomatic adults over age 50 undergoing
      unsedated flexible sigmoidoscopy screening, use of a colonoscope instead of a
      sigmoidoscope was studied to determine the feasibility, safety, tolerability, and
      yield. METHODS: Over an 18-month period, asymptomatic adults referred for
      colorectal cancer screening by sigmoidoscopy were enrolled. Two experienced
      nurses attempted to reach the cecum by using a pediatric colonoscope but stopped
      if significant discomfort was experienced, if the preparation was suboptimal, or
      if polyps were found. RESULTS: A total of 672 adults (652 men, 20 women)
      underwent screening. The colonoscope was advanced beyond the level attainable
      with a sigmoidoscope (70-cm mark) in 240 cases. The cecum was reached in 110
      (16.4%) of these patients, with a mean pain intensity for patients of 2.6 (scale
      1-10) and a mean time for completion of the procedure of 17 minutes. Colonoscopy
      to the cecum was not feasible because of patient discomfort in 280 patients
      (41.7%), poor preparation in 179 (26.7%), left-sided polyps or cancer in 69,
      and/or severe diverticulosis and tortuosity in 34 cases. Twenty patients had
      polyps proximal to the 70-cm mark (65% adenomas, no cancer). There was no
      complication. CONCLUSIONS: The use of a colonoscope instead of a sigmoidoscope by
      nurses performing unsedated screening sigmoidoscopy is feasible, safe, and well
      tolerated, and may improve the yield for screening by at least 16.4% in patients
      who would otherwise have had only the left colon examined.

PMID- 14595310
TI  - Propofol for endoscopic sedation: A protocol for safe and effective
      administration by the gastroenterologist.
AB  - BACKGROUND: There is increasing interest in the use of propofol, an ultrashort
      acting hypnotic agent, for sedation during endoscopic examinations. A protocol
      was developed for administration of propofol, combined with small doses of
      midazolam and meperidine, for endoscopic sedation under the direction of a
      gastroenterologist. Initial experience with using this protocol is described.
      METHODS: A total of 819 consecutive endoscopic examinations under sedation with
      propofol, midazolam, and meperidine (or fentanyl), in adherence with the sedation
      protocol, were reviewed retrospectively. RESULTS: There were 638 colonoscopies
      and 181 EGDs; 89% of patients were classified as American Society of
      Anesthesiologists (ASA) class I or II. Mean dosages of medications were: propofol
      63 (33.5) mg, meperidine 48 (7.2) mg, and midazolam 1 (0.12) mg. The dose of
      propofol was inversely correlated with age and ASA class, and positively
      correlated with patient weight and duration of examination. Hypotension (>20 mm
      Hg decline in either systolic or diastolic blood pressure) developed in 218 (27%)
      patients, and hypoxemia (oxygen saturation <90%) developed in 75 (9%). All
      episodes of hypotension and hypoxemia were transient, and no patient required
      administration of a pharmacologic antagonist or assisted ventilation. The average
      time for recovery after colonoscopy and after EGD was, respectively, 25 minutes
      and 28 minutes. All EGDs and 98% of colonoscopies were completed successfully.
      CONCLUSIONS: On the basis of this initial experience, it is believed that
      propofol, potentiated by small doses of midazolam and meperidine, can be safely
      and effectively administered under the direction of a gastroenterologist.
      Additional research will be necessary to determine whether propofol is superior
      to the current methods of sedation.

PMID- 14595311
TI  - Percutaneous transhepatic cholangioscopic treatment of patients with benign bilio
      enteric anastomotic strictures.
AB  - BACKGROUND: Percutaneous transhepatic cholangioscopy is a nonoperative method for
      accessing bilio-enteric anastomotic strictures that cannot be reached via the
      transpapillary route. This study evaluated the immediate and long-term results of
      treatment via percutaneous transhepatic cholangioscopy of patients with benign
      bilio-enteric anastomotic strictures. METHODS: A retrospective analysis was
      conducted of 21 patients who, between October 1994 and March 2001, had undergone
      percutaneous transhepatic cholangioscopy for bilio-enteric anastomotic
      strictures. Follow-up ranged from 12 to 79 months (mean 33.3 months). RESULTS:
      The initial technical success rate was 100%, and the short-term morbidity and
      mortality rates were, respectively, 14.3% and 0%. However, strictures recurred in
      8 patients (38.1%) at a mean of 17.1 months (range 2-38 months). The success rate
      exclusive of patients with recurrent strictures was 61.9%, and the overall
      success rate was 81.0% when the procedures were repeated. The long-term morbidity
      rate was 38.1%, but most complications resolved with conservative treatment. In
      17 patients (81.0%), strictures were complicated by biliary stones, and these
      were successfully treated via percutaneous transhepatic cholangioscopy (stone
      removal rate 94.1%, recurrence rate 37.5%). CONCLUSIONS: Percutaneous
      transhepatic cholangioscopy-based treatment of patients with benign bilio-enteric
      anastomotic strictures is safe and effective. This minimally invasive method
      frequently can be used as a substitute for surgery.

PMID- 14595313
TI  - Calculating the benefit of a negative endoscopy.

PMID- 14595312
TI  - Complications of enteral access.

PMID- 14595314
TI  - Fatal gastroduodenal artery bleeding.

PMID- 14595315
TI  - Spontaneous esophageal hematoma.

PMID- 14595316
TI  - Klippel-Trenaunay-Weber syndrome and duodenal hemorrhage.

PMID- 14595317
TI  - Incarcerated inguinal hernia.

PMID- 14595318
TI  - Crohn's disease and volvulus.

PMID- 14595319
TI  - Duodenal stent migration.

PMID- 14595320
TI  - Ablation therapy for Barrett's esophagus.

PMID- 14595322
TI  - A novel endoscopic full-thickness plicator for the treatment of GERD: A pilot
      study.
AB  - BACKGROUND: The novel full-thickness plication described in this study was
      designed to inhibit gastroesophageal reflux by placement of a transmural
      plication near the gastroesophageal junction under direct endoscopic
      visualization. The resulting serosa-to-serosa tissue union is thought to
      accentuate and restore the valvular mechanism of the gastroesophageal junction.
      The aim of this study was to assess the safety and feasibility of endoscopic full
      thickness plication for the treatment of patients with GERD symptoms. METHODS: A
      pilot study was performed in patients with chronic heartburn and pathologic
      reflux requiring maintenance antisecretory therapy. A single full-thickness
      plication was placed in the gastric cardia within 1 to 2 cm of the
      gastroesophageal junction. The primary end points of the study were procedure
      safety and feasibility, as well as long-term durability of the full-thickness
      tissue fixation. Secondary end points included medication use and the GERD-Health
      Related Quality of Life questionnaire and Gastrointestinal Symptom Rating Scale.
      RESULTS: Full-thickness plication was performed successfully in 6 of 7 patients,
      with one procedure aborted because of difficulty in sedating the patient. Mean
      procedure time was 21 minutes. Mild epigastric pain was reported by two patients
      and difficulty with eructation by one patient; all symptoms resolved
      spontaneously within 7 days of the procedure. Endoscopy at 6 months revealed an
      intact plication in all patients. At 1 year after the procedure, patients
      reported sustained reduction in heartburn scores. One patient, who did not
      experience significant relief of symptoms, ultimately underwent successful
      laparoscopic Nissen fundoplication at 6 months after the procedure. At 1 year
      after the procedure, 3 of 5 patients were not taking anti-GERD medications.
      CONCLUSIONS: Endoscopic full-thickness plication is feasible, safe and, in this
      pilot study, appeared to reduce symptoms and medication use associated with GERD.

PMID- 14595323
TI  - In vivo evaluation of a new bioabsorbable self-expanding biliary stent.
AB  - BACKGROUND: Bioabsorbable stents may offer advantages for the treatment of benign
      and malignant biliary strictures, including large stent diameter, decreased
      biofilm accumulation and proliferative changes, elimination of the need for stent
      removal and imaging artifacts, and prospects for drug impregnation. However,
      suboptimal expansion has hampered prior iterations. A new bioabsorbable biliary
      stent (BioStent) was evaluated in a porcine model. METHODS: BioStents were placed
      in 8 animals for long-term follow-up. The following were evaluated: accuracy and
      ease of delivery and deployment, radial expansion, and radiologic visualization.
      Stent function and biotolerance were assessed by cholangiography, serum
      bilirubin, and necropsy for histopathology performed in pairs at 2, 4, 6, and 12
      months. RESULTS: Stents were delivered without sphincterotomy and were deployed
      easily, accurately, and with good immediate stent expansion and radiographic
      visualization. On follow-up, all stents were fully expanded and serum bilirubin
      levels remained within the normal range. Although there was no clinical evidence
      of biliary obstruction, filling defects were common at cholangiography. On
      histopathologic evaluation, there was neither bile duct integration or
      proliferative change. CONCLUSIONS: The BioStent bioabsorbable biliary stent,
      modified with axial runners, can be effectively deployed endoscopically, is self
      expanding, is visualized radiographically, and remains patent up to 6 months.
      There was no bile duct integration or proliferative change, which are potential
      advantages. Stent occlusion and migration remain concerns.

PMID- 14595324
TI  - EUS-guided FNA of pancreatic metastasis from renal cell carcinoma.
AB  - BACKGROUND: The prognosis for patients with renal cell carcinoma metastatic to
      the pancreas is better than that for patients with primary pancreatic
      adenocarcinoma. In patients with a history of renal cell cancer, it would,
      therefore, appear necessary to obtain cytologic or histopathologic evidence of
      the tumor type. EUS-guided FNA is considered the technique of choice for this
      purpose. This study retrospectively assessed the efficacy of EUS-guided FNA and
      specific technical considerations when the procedure is performed for this
      indication. METHODS: Over 2 years, EUS-guided FNA was performed in 11 consecutive
      patients with a history of renal cell carcinoma and a solid mass within the
      pancreas. OBSERVATIONS: After EUS-guided FNA yielded a negative result in two
      patients, the sampling technique was modified, namely short aspiration with low
      negative vacuum pressure. This resulted in the detection of metastases of renal
      cell cancer in the remaining 9 patients. There was no procedure-related
      complication. CONCLUSIONS: EUS-guided FNA is safe and accurate for the diagnosis
      of pancreatic metastases of renal cell carcinoma. However, effective sampling
      requires techniques that differ from those used for solid pancreatic masses.

PMID- 14595325
TI  - Endoscopic sphincterotomy in adult hemophiliac patients with choledocholithiasis.
AB  - BACKGROUND: The aim of this study was to investigate the risk of bleeding in
      adult hemophiliac patients undergoing endoscopic sphincterotomy for
      choledocholithiasis. METHODS: From 1983 to 2002, 7 patients with hemophilia A and
      two with hemophilia B were referred for endoscopic sphincterotomy and extraction
      of bile duct stones. The degree of hemophilia was mild in 4 patients, moderate in
      3, and severe in two. Pre-admission levels of blood clotting factors ranged from
      less than 1% to 18%. Levels of the deficient factors were monitored carefully
      before and after sphincterotomy, and the relevant factor was replaced to achieve
      100% activity before and for 24 hours after endoscopic sphincterotomy.
      OBSERVATIONS: Seven patients had factor replacement every 8 hours, and two
      received continuous infusions. No patient developed bleeding after
      sphincterotomy. At discharge, 48 hours after the procedure, patients who had
      received continuous infusions had a factor level of greater than 90%; those who
      had received intermittent replacement had levels of greater than 50%. After
      discharge, the patients were treated with regular infusion of the deficient
      factor for 15 days. CONCLUSIONS: With adequate preoperative and post-procedure
      monitoring of clotting factors, meticulous attention to hemostasis during
      sphincterotomy, careful post-procedure monitoring, and timely replacement
      therapy, patients with hemophilia can undergo endoscopic sphincterotomy without
      bleeding complications.

PMID- 14595326
TI  - Migration of covered biliary self-expanding metallic stents in two patients with
      malignant biliary obstruction.

PMID- 14595327
TI  - Successful management of bleeding duodenal varices by endoscopic variceal
      ligation and balloon-occluded retrograde transvenous obliteration.

PMID- 14595328
TI  - Embolotherapy for small bowel angiodysplasia.

PMID- 14595329
TI  - Santorinicele without pancreas divisum.

PMID- 14595330
TI  - Endoscopic tattooing facilitates repeated localization and endoscopic therapy of
      a difficult-to-find minor papilla in pancreas divisum.

PMID- 14595336
TI  - An archaeal endoribonuclease catalyzes cis- and trans- nonspliceosomal splicing
      in mouse cells.
AB  - The tRNA endonuclease from the archaebacterium Methanococcus jannaschii (MJ
      endonuclease) can cleave RNAs forming specific bulge-helix-bulge (BHB) structures
      recognized by the enzyme. The resulting cleavage products are subsequently joined
      together by an endogenous ligase. We demonstrate the potential of using this
      strategy for repairing RNA in higher organisms by expressing the enzyme in mouse
      cells. Reporter target mRNAs modified with 17-nucleotide introns, flanked by
      sequences capable of forming BHB structures in cis, were expressed in mouse
      cells. RNA molecules that can form BHB substrates in trans with targeted mRNAs
      were also designed. Co-transfection of mouse cells with plasmids expressing these
      RNAs and the MJ endonuclease led to formation of RNA chimeras in which the target
      and exogenous RNA were recombined across the BHB. This technology is not limited
      to mRNA, but could in principle be used to destroy, modify or restore the
      function of a vast repertoire of RNA species or to join selectable tags to target
      RNAs.

PMID- 14595337
TI  - Out of the shadows.

PMID- 14595335
TI  - Citron-N is a neuronal Rho-associated protein involved in Golgi organization
      through actin cytoskeleton regulation.
AB  - The actin cytoskeleton is best known for its role during cellular morphogenesis.
      However, other evidence suggests that actin is also crucial for the organization
      and dynamics of membrane organelles such as endosomes and the Golgi complex. As
      in morphogenesis, the Rho family of small GTPases are key mediators of organelle
      actin-driven events, although it is unclear how these ubiquitously distributed
      proteins are activated to regulate actin dynamics in an organelle-specific
      manner. Here we show that the brain-specific Rho-binding protein Citron-N is
      enriched at, and associates with, the Golgi apparatus of hippocampal neurons in
      culture. Suppression of the whole protein or expression of a mutant form lacking
      the Rho-binding activity results in dispersion of the Golgi apparatus. In
      contrast, high intracellular levels induce localized accumulation of RhoA and
      filamentous actin, protecting the Golgi from the rupture normally produced by
      actin depolymerization. Biochemical and functional analyses indicate that Citron
      N controls actin locally by assembling together the Rho effector ROCK-II and the
      actin-binding, neuron-specific, protein Profilin-IIa (PIIa). Together with recent
      data on endosomal dynamics, our results highlight the importance of organelle
      specific Rho modulators for actin-dependent organelle organization and dynamics.

PMID- 14595338
TI  - US NHGRI launches chemical attack on drug development gap.

PMID- 14595339
TI  - Public-private partnerships boost research on neglected diseases.

PMID- 14595340
TI  - Concerns raised over declining antiinfectives R&D.

PMID- 14595342
TI  - GM confusion in Brazil.

PMID- 14595343
TI  - Benefits of biotech clusters questioned.

PMID- 14595344
TI  - Biotech parks proliferate, despite concerns over sustainability.

PMID- 14595346
TI  - Equivocal role of micelles in Eprex adverse events.

PMID- 14595347
TI  - Equivocal role of micelles in Eprex adverse events.

PMID- 14595348
TI  - Chaperonins govern growth of Escherichia coli at low temperatures.

PMID- 14595349
TI  - Invention and commercialization in optical bioimaging.

PMID- 14595350
TI  - Crystal gazing in optical microscopy.

PMID- 14595351
TI  - A framework for designing transgenic crops--science, safety and citizen's
      concerns.

PMID- 14595352
TI  - Gene medication or genetic modification? The devil is in the details.

PMID- 14595353
TI  - The tyranny of 'genethics'.

PMID- 14595356
TI  - The rise of European venture capital for biotechnology.

PMID- 14595357
TI  - Engineering better cytokines.

PMID- 14595358
TI  - Sequence of a symbiont.

PMID- 14595359
TI  - Reconstructing genetic networks in yeast.

PMID- 14595360
TI  - Playing tag with the yeast proteome.

PMID- 14595362
TI  - Toward fluorescence nanoscopy.
AB  - For more than a century, the resolution of focusing light microscopy has been
      limited by diffraction to 180 nm in the focal plane and to 500 nm along the optic
      axis. Recently, microscopes have been reported that provide three- to sevenfold
      improved axial resolution in live cells. Moreover, a family of concepts has
      emerged that overcomes the diffraction barrier altogether. Its first exponent,
      stimulated emission depletion microscopy, has so far displayed a resolution down
      to 28 nm. Relying on saturated optical transitions, these concepts are limited
      only by the attainable saturation level. As strong saturation should be feasible
      at low light intensities, nanoscale imaging with focused light may be closer than
      ever.

PMID- 14595363
TI  - Second-harmonic imaging microscopy for visualizing biomolecular arrays in cells,
      tissues and organisms.
AB  - Although the nonlinear optical effect known as second-harmonic generation (SHG)
      has been recognized since the earliest days of laser physics and was demonstrated
      through a microscope over 25 years ago, only in the past few years has it begun
      to emerge as a viable microscope imaging contrast mechanism for visualization of
      cell and tissue structure and function. Only small modifications are required to
      equip a standard laser-scanning two-photon microscope for second-harmonic imaging
      microscopy (SHIM). Recent studies of the three-dimensional in vivo structures of
      well-ordered protein assemblies, such as collagen, microtubules and muscle
      myosin, are beginning to establish SHIM as a nondestructive imaging modality that
      holds promise for both basic research and clinical pathology. Thus far the best
      signals have been obtained in a transmitted light geometry that precludes in vivo
      measurements on large living animals. This drawback may be addressed through
      improvements in the collection of SHG signals via an epi-illumination microscope
      configuration. In addition, SHG signals from certain membrane-bound dyes have
      been shown to be highly sensitive to membrane potential. Although this indicates
      that SHIM may become a valuable tool for probing cell physiology, the small
      signal size would limit the number of photons that could be collected during the
      course of a fast action potential. Better dyes and optimized microscope optics
      could ultimately lead to the imaging of neuronal electrical activity with SHIM.

PMID- 14595364
TI  - Optical coherence tomography for ultrahigh resolution in vivo imaging.
AB  - Optical coherence tomography (OCT) is an emerging biomedical optical imaging
      technique that performs high-resolution, cross-sectional tomographic imaging of
      microstructure in biological systems. OCT can achieve image resolutions of 1-15
      microm, one to two orders of magnitude finer than standard ultrasound. The image
      penetration depth of OCT is determined by the optical scattering and is up to 2-3
      mm in tissue. OCT functions as a type of 'optical biopsy' to provide cross
      sectional images of tissue structure on the micron scale. It is a promising
      imaging technology because it can provide images of tissue in situ and in real
      time, without the need for excision and processing of specimens.

PMID- 14595365
TI  - Nonlinear magic: multiphoton microscopy in the biosciences.
AB  - Multiphoton microscopy (MPM) has found a niche in the world of biological imaging
      as the best noninvasive means of fluorescence microscopy in tissue explants and
      living animals. Coupled with transgenic mouse models of disease and 'smart'
      genetically encoded fluorescent indicators, its use is now increasing
      exponentially. Properly applied, it is capable of measuring calcium transients
      500 microm deep in a mouse brain, or quantifying blood flow by imaging shadows of
      blood cells as they race through capillaries. With the multitude of possibilities
      afforded by variations of nonlinear optics and localized photochemistry, it is
      possible to image collagen fibrils directly within tissue through nonlinear
      scattering, or release caged compounds in sub-femtoliter volumes.

PMID- 14595366
TI  - Near-field optics: from subwavelength illumination to nanometric shadowing.
AB  - Near-field optics uniquely addresses problems of x, y and z resolution by
      spatially confining the effect of a light source to nanometric domains. The
      problems in using far-field optics (conventional optical imaging through a lens)
      to achieve nanometric spatial resolution are formidable. Near-field optics serves
      a bridging role in biology between optical imaging and scanned probe microscopy.
      The integration of near-field and scanned probe imaging with far-field optics
      thus holds promise for solving the so-called inverse problem of optical imaging.

PMID- 14595367
TI  - FRET imaging.
AB  - Forster (or Fluorescence) Resonance Energy Transfer (FRET) is unique in
      generating fluorescence signals sensitive to molecular conformation, association,
      and separation in the 1-10 nm range. We introduce a revised photophysical
      framework for the phenomenon and provide a systematic catalog of FRET techniques
      adapted to imaging systems, including new approaches proposed as suitable
      prospects for implementation. Applications extending from a single molecule to
      live cells will benefit from multidimensional microscopy techniques, particularly
      those adapted for optical sectioning and incorporating new algorithms for
      resolving the component contributions to images of complex molecular systems.

PMID- 14595370
TI  - Past versus present: the importance of tense in patent application examples.

PMID- 14595374
TI  - Professional master's degree programs in regulatory affairs and biomedical
      quality systems.
AB  - Two new programs are designed to supply biotechnology professionals with industry
      specific skills required for successful biomedical product development.

PMID- 14595375
TI  - Structural adaptability in the ligand-binding pocket of the ecdysone hormone
      receptor.
AB  - The ecdysteroid hormones coordinate the major stages of insect development,
      notably moulting and metamorphosis, by binding to the ecdysone receptor (EcR); a
      ligand-inducible nuclear transcription factor. To bind either ligand or DNA, EcR
      must form a heterodimer with ultraspiracle (USP), the homologue of retinoid-X
      receptor. Here we report the crystal structures of the ligand-binding domains of
      the moth Heliothis virescens EcR-USP heterodimer in complex with the ecdysteroid
      ponasterone A and with a non-steroidal, lepidopteran-specific agonist BYI06830
      used in agrochemical pest control. The two structures of EcR-USP emphasize the
      universality of heterodimerization as a general mechanism common to both
      vertebrates and invertebrates. Comparison of the EcR structures in complex with
      steroidal and non-steroidal ligands reveals radically different and only
      partially overlapping ligand-binding pockets that could not be predicted by
      molecular modelling and docking studies. These findings offer new perspectives
      for the design of insect-specific, environmentally safe insecticides. The concept
      of a ligand-dependent binding pocket in EcR provides an insight into the moulding
      of nuclear receptors to their ligand, and has potential applications for human
      nuclear receptors.

PMID- 14595377
TI  - Lack of enantioselectivity of herpes virus thymidine kinase allows safer imaging
      of gene delivery.
AB  - Herpes simplex virus thymidine kinase (HSV-TK) is widely used in gene therapy.
      The enzymatic activity of HSV-TK may be traced in vivo by specific
      radiopharmaceuticals in order to image transgene expression. However, most of
      these radiopharmaceuticals are toxic per se or after activation by HSV-TK, and
      therefore do not represent ideal molecules for clinical applications and repeated
      imaging. Unlike human cytosolic TK, HSV-TK is not enantioselective and can
      efficiently phosphorylate both D and L enantiomers of beta-thymidine. Here we
      show that, after phosphorylation by HSV-TK, tritiated L-beta-thymidine (LT) is
      selectively retained inside the cells in vitro and in vivo. We used the in vivo
      accumulation of radioactive phosphorylated LT to image the HSV-TK-positive cells
      inside a transplantable murine brain tumour after inoculation of cells producing
      retroviruses carrying HSV-TK. Owing to their unnatural enantiomeric conformation,
      phosphorylated LT metabolites are very poorly processed by mammalian enzymes,
      thus leading to increased cellular retention and minimal toxicity. The ability to
      image cells expressing the HSV-TK gene by using radiolabelled LT, without
      damaging the cells accumulating the phosphorylated L-nucleoside, will be
      important to monitor the levels and spatial distribution of therapeutic vectors
      carrying HSV-TK.

PMID- 14595378
TI  - Intravascular naked DNA vaccine encoding glycoprotein B induces protective
      humoral and cellular immunity against herpes simplex virus type 1 infection in
      mice.
AB  - Naked plasmid DNA (pDNA) vaccine expressing herpes simplex virus type 1 (HSV-1)
      glycoprotein B (gB) was tested for protective activity against acute HSV-1
      infection in mice. The pDNA was intravenously injected into Balb/c mice via their
      tail vein under high pressure, and the vaccination was performed two times at an
      interval of 7 days. The gB gene vaccination significantly protected the mice from
      subsequent intraperitoneal challenge with a lethal dose of HSV-1, which killed
      all the animals given control plasmid or saline. The protective activity was
      correlated with the dose of the plasmid inoculated, the survival rate reaching
      83% in mice vaccinated with 5 microg of pDNA. The vaccinated mice were also
      protected from latent HSV infection. The immunized mice showed significant
      elevation in neutralizing antibody against HSV-1 as well as serum levels of
      interleukin-12 (IL-12) and interferon-gamma (IFN-gamma). When mice were immunized
      with 5 microg of an Epstein-Barr virus (EBV)-based plasmid vector harboring the
      gB, the cytotoxic T lymphocytes (CTLs) activity and proliferative response for
      HSV-1 were also induced. The results strongly suggest that intravenous
      immunization of naked pDNA may induce humoral and cellular immune responses
      against the virus, leading to a significant prophylactic outcome against HSV-1
      infection in mice.

PMID- 14595379
TI  - The cationic region from HIV tat enhances the cell-surface expression of
      epitope/MHC class I complexes.
AB  - The potential of genetic immunization has been acknowledged for almost a decade,
      but disappointing immunogenicity in humans has delayed its introduction into the
      clinical arena. To try to increase the potency of genetic immunization, we and
      others have evaluated 'translocatory' proteins, which are thought to exit living
      cells by an uncharacterized pathway, and enter neighboring cells in an energy
      independent manner. Several laboratories, including our own, have begun to
      question these remarkable properties. Our previous studies showed that the
      ability of an epitope to induce major histocompatibility complex (MHC) class I
      restricted CD8(+) T cells was, indeed, enhanced by its being attached to the
      proposed translocatory sequence of the HIV-1 tat protein. However, we found
      little evidence that the increased immunogenicity resulted from transfer of the
      fusion peptide between living cells, and we proposed that it resulted instead
      from an increased epitope/MHC expression on the surface of transfected cells.
      Here, we directly test this hypothesis. We show that cells cotransfected with
      plasmids encoding an epitope, and the relevant MHC class I allele, can stimulate
      epitope-specific T cells, and that attachment of the epitope to a putative
      translocatory sequence - which we term herein an 'integral cationic region' (ICR)
      - leads to a marked increase in stimulatory activity. This elevated stimulatory
      capacity does not result from a nonspecific increase in MHC class I expression.
      We use a high-affinity T-cell receptor (TcR) specific for the epitope/MHC
      combination to quantitate directly the cell-surface expression of the immunogenic
      complex, and we show that the attachment of the tat ICR to an epitope results in
      a substantial enhancement of its cell-surface presentation. These data suggest an
      alternative explanation for the immune enhancement seen with ICRs.

PMID- 14595381
TI  - Regression of solid tumors by engineered overexpression of von Hippel-Lindau
      tumor suppressor protein and antisense hypoxia-inducible factor-1alpha.
AB  - The von Hippel-Lindau tumor suppressor protein (pVHL) suppresses tumor formation
      by binding the alpha subunits of hypoxia-inducible factors (HIFs) responsible for
      stimulating tumor angiogenesis and glycolysis, targeting them for ubiquitination
      and proteasomal destruction. Loss of pVHL leads to the development of sporadic
      renal cell carcinomas (RCCs). In the present study, we sought to determine
      whether engineered overexpression of pVHL in tumors other than RCC can inhibit
      tumor growth, either as a monotherapy, or in combination with antisense HIF
      1alpha therapy. Intratumoral injection of subcutaneous EL-4 thymic lymphomas with
      an expression plasmid encoding pVHL resulted in the downregulation of HIF-1alpha
      and vascular endothelial growth factor (VEGF). There was a concomitant reduction
      in tumor angiogenesis and increased tumor cell apoptosis due in part to
      downregulation of Bcl-2 expression. VHL therapy resulted in the complete
      regression of small (0.1 cm diameter) tumors whereas, in contrast, large (0.4 cm
      diameter) EL-4 tumors were only slowed in their growth. Nevertheless, large
      tumors completely regressed in response to intratumoral injection of a
      combination of antisense HIF-1alpha and VHL plasmids. Combination therapy
      resulted in increased losses of HIF-1alpha, VEGF, and tumor blood vessels, and
      increased tumor cell apoptosis. These novel results suggest that synergistic
      therapies that simultaneously block the expression or function of HIF-1alpha, and
      enhance the expression or function of VHL may be beneficial in the treatment of
      cancer.

PMID- 14595380
TI  - Imaging the spatial distribution of transgene expression in the lungs with
      positron emission tomography.
AB  - This study was designed to evaluate the utility of positron emission tomography
      (PET) to quantify the magnitude and spatial distribution of transgene expression
      after different methods of adenoviral vector delivery (with surfactant- and
      saline-based vehicles) within rat lungs. In all, 17 animals (eight in the
      surfactant group, nine in the saline group) were studied 3 days after
      intratracheal administration of a replication-incompetent adenovirus encoding a
      mutant Herpes simplex virus-1 thymidine kinase (mHSV1-TK)-enhanced green
      fluorescent protein fusion gene driven by a Cytomegalovirus promoter (Ad-CMV-mNLS
      HSV1sr39tk-egfp). PET images were obtained 1 h after i.v. administration of 9-(4
      [(18)F]-fluoro-3-hydroxymethylbutyl)guanine ([(18)F]-FHBG), an imaging substrate
      for mHSV1-TK. Overall, the average lung concentration of [(18)F]-FHBG was
      significantly greater in the surfactant group than in the saline group (0.24+/
      0.06 versus 0.17+/-0.03% injected dose/ml lung, P< or =0.05). Lung [(18)F]-FHBG
      distribution was more peripheral and more homogeneous in the surfactant group
      than in the saline group (mean coefficient of variation=31+/-4 versus 36+/-3%,
      respectively, P< or =0.05). Regions of increased tracer concentration in the
      surfactant group compared to the saline group were evenly distributed throughout
      the lungs. We conclude that PET imaging provides useful and meaningful
      information about the effectiveness of different gene transfer delivery
      strategies within the lungs, and that surfactant-based vehicles may be a superior
      strategy for pulmonary gene transfer.

PMID- 14595382
TI  - Targeting of biotinylated compounds to its target tissue using a low-density
      lipoprotein receptor-avidin fusion protein.
AB  - The very high binding affinity of avidin to biotin is one of the highest to occur
      in nature. We constructed a fusion protein composed of avidin and the endocytotic
      LDL receptor in order to target biotinylated molecules to cells of the desired
      tissues. In addition to the native avidin, charge-mutated and nonglycosylated
      avidins were utilized as part of the fusion proteins, in order to modify its
      properties. All of the fusion protein versions retained the biotin-binding
      capacity. Although the specificity was not increased, however, fusion proteins
      composed of natural avidin and nonglycosylated avidin bound most efficiently to
      the biotinylated ligands. Fluorescence microscopy and atomic force microscopy
      studies revealed the expression of the fusion protein on cell membranes, and
      demonstrated specific and high-affinity binding of biotin to the low-density
      lipoprotein receptor (LDLR)-avidin fusion protein in vitro. Additionally,
      systemically administered biotinylated ligand targeted with high specificity the
      intracerebral tumors of rats that were expressing fusion protein after the virus
      mediated gene transfer. These results suggest that local gene transfer of the
      fusion protein to target tissues may offer a novel tool for the delivery of
      biotinylated molecules in vitro and in vivo for therapeutic and imaging purposes.

PMID- 14595383
TI  - In vivo adenovirus-mediated delivery of a uPA/uPAR antagonist reduces retinal
      neovascularization in a mouse model of retinopathy.
AB  - Diabetic retinopathy and retinopathy of prematurity are among the leading causes
      of vision impairment throughout the world. Both diseases are characterized by
      pathological angiogenesis, which severely impairs vision. Extracellular
      proteinases play important roles in endothelial cell migration during
      angiogenesis. Amino-terminal fragment (ATF) is an angiostatic molecule that
      targets the uPA/uPAR system and inhibits endothelial cell migration. The
      angiostatic effect of ATF has been demonstrated in models of cancer, but has
      never been assessed in pathological retinal neovascularization. Endostatin also
      has angiostatic effects on tumor growth and retinal neovascularization. We used
      an adenoviral vector carrying the murine ATF (AdATFHSA) or endostatin gene
      coupled to human serum albumin (HSA) (AdEndoHSA) to increase the half-life of the
      therapeutic protein in the circulation. We induced retinopathy by exposing 7-day
      old mice to high levels of oxygen. They were intravitreally injected with the
      vectors. Local injection of AdATFHSA or AdEndoHSA reduced retinal
      neovascularization by 78.1 and 79.2%, respectively. Thus, the adenovirus-mediated
      delivery of ATFHSA or EndoHSA reduces retinal neovascularization in a mouse model
      of hypoxia-induced neovascularization.

PMID- 14595384
TI  - Myeloablative conditioning regimens for AML allografts: 30 years later.
AB  - During the last three decades, several myeloablative conditioning regimens have
      been used for AML allografts. In this review, we systematically examine the data
      from studies reporting on myeloablative conditioning regimens for AML allografts.
      High-dose busulfan combined with cyclophosphamide (BuCy) and cyclophosphamide in
      combination with total body irradiation (CyTBI) are the two most commonly used
      conditioning regimens for AML allografts. From the available data, there are no
      significant differences in survival with these two regimens. A small benefit of
      decreased relapse rate with CyTBI is counterbalanced by a nonsignificant increase
      in treatment-related mortality. The incidence of veno-occlusive disease is
      significantly higher in patients treated with BuCy. Therapeutic monitoring of
      busulfan was not reported in any of the studies comparing the regimens. Either of
      the regimens can be used for AML allografts, and the choice may ultimately depend
      on local availability and expertise. Further improvements may be possible from
      modifications of the standard regimens. Data from these latter studies seem to be
      encouraging, but are not based on comparative randomized trials.

PMID- 14595385
TI  - In children and adolescents, the pharmacodynamics of high-dose busulfan is
      dependent on the second alkylating agent used in the combined regimen (melphalan
      or thiotepa).
AB  - A strong relationship has been demonstrated between high systemic exposure to
      busulfan and the occurrence of hepatic veno-occlusive disease (HVOD) after a
      busulfan-cyclophosphamide regimen (BU CY). We report a prospective study aimed at
      exploring the pharmacodynamics of high-dose busulfan combined with either
      melphalan (BU MEL) or thiotepa (BU TTP) followed by autologous stem cell
      transplantation in children and adolescents with a malignant solid tumor.
      Busulfan was given orally at a total dose of 600 mg m(-2). In all, 45 patients
      with a median age of 6.3 years were included in the study: 25 received BU MEL and
      20 received BU TTP. The incidence of HVOD was 44% (CI 95% [23-65%]) in the BU MEL
      group and 25% (CI95% [9-49%]) in the BU TTP group. In the BU TTP group, patients
      who developed HVOD had a significantly higher AUC 0-6 h after the 13th dose
      (6201+/-607 h ng ml(-1)) than those who did not (5024+/-978 h ng ml(-1))
      (P<0.05). In the BU MEL group, there was no difference in terms of systemic
      exposure to busulfan between patients who developed HVOD and those who did not.
      In conclusion, the guidelines established for monitoring BU CY cannot be
      extrapolated when busulfan is combined with another drug.

PMID- 14595386
TI  - Peripheral blood is safer than bone marrow as a source of hematopoietic
      progenitors in patients with myelodysplastic syndromes who receive an allogeneic
      transplantation. Results from the Spanish registry.
AB  - Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative
      therapy for patients with myelodysplastic syndromes (MDSs). We have analyzed the
      outcome of 81 patients who underwent an allogeneic transplant from an HLA
      identical sibling donor. The overall survival (OS) was 31% and disease-free
      survival was 30% at 5.8 years. Transplant-related complications were the cause of
      death in 44% and disease progression in 16% of patients. Acute graft-versus-host
      disease (aGVHD) grades II-IV occurred in 32 cases (39%). Extensive chronic GVHD
      (cGVHD) was observed in 27% of patients. When the log-rank test was performed, we
      observed that patients transplanted more than 6 months after diagnosis, and those
      transplanted with bone marrow (BM) displayed a shorter survival (P=0.009 and
      0.005, respectively). Patients who developed cGVHD showed a trend towards better
      OS (P=0.07). Patients receiving BM had a higher incidence of aGVHD (65 vs 50%)
      and less cGVHD (52 vs 30%), although the differences did not reach statistical
      significance. Moreover, patients who received PB-HSC displayed a faster
      engraftment (P=0.000) and showed a significantly lower early transplant-related
      mortality (14 vs 42%; P=0.006) and longer OS (P=0.005). In summary, our results
      show that hematopoietic transplantation should be performed as soon as possible
      in MDS patients and that PB is preferable to BM as a source of HSC.

PMID- 14595387
TI  - Allogeneic bone marrow transplantation for chronic myeloid leukemia in childhood:
      a report from the Societe Francaise de Greffe de Moelle et de Therapie Cellulaire
      (SFGM-TC).
AB  - To determine the results of allogeneic hematopoietic stem cell (HSC)
      transplantation for chronic myelogenous leukemia (CML) at various stages of the
      disease in children, a retrospective analysis was carried out on the outcome of
      transplants performed on 76 children and teenagers with CML between 1982 and
      1998. In all, 60 patients were transplanted from a matched sibling donor (MSD)
      and 16 from a matched unrelated donor (MUD). There was a higher incidence of
      acute graft-versus-host disease after MUD transplantation (P<10(-3)). The main
      cause of death was transplant-related toxicity in both groups. In MSD recipients,
      the probability of relapse at 5 years for patients transplanted in the first
      chronic phase was lower than in patients transplanted in the advanced phase
      (relative risk (rr)=5.90; 95% confidence interval (CI), 1.85-18.82, P<0.01). The
      estimated 5-year event-free survival (EFS) rate was higher after MSD vs MUD
      transplantation (61% (95% CI, 48-73%) vs 27% (95% CI, 4-49%), rr=0.25, P<10(-3)).
      In children transplanted from MSD, the 5-year EFS was higher when transplantation
      was performed in the first chronic phase vs the advanced phases (73% (95% CI, 59
      87%) vs 32% (95% CI, 10-54%), P<10(-3)). Disease status at transplantation was
      the unique factor influencing survival in patients undergoing transplantation
      from MSD with a better outcome for those transplanted in the first chronic phase.
      Allogeneic HSC offers a possibility of curing childhood CML with a significant
      advantage for patients transplanted in chronic phase using a human leukocyte
      antigen-identical sibling donor.

PMID- 14595388
TI  - Factors affecting reconstitution of the T cell compartment in allogeneic
      haematopoietic cell transplant recipients.
AB  - The factors affecting T cell reconstitution post haematopoietic cell
      transplantation (HCT) are not well characterised. We carried out a longitudinal
      analysis of T cell reconstitution in 32 HCT recipients during the first 12 months
      post transplant. We analysed reconstitution of naive, memory and effector T
      cells, their diversity and monitored thymic output using TCR rearrangement
      excision circles (TRECs). Thymic-independent pathways were responsible for the
      rapid reconstitution of memory and effector T cells less than 6 months post HCT.
      Thymic-dependent pathways were activated between 6 and 12 months in the majority
      of patients with naive T cell numbers increasing in parallel with TREC levels.
      Increasing patient age, chronic GVHD and T cell depletion (with or without
      pretransplant Campath-1H) predicted low TREC levels and slow naive T cell
      recovery. Furthermore, increasing patient age also predicted high memory and
      effector T cell numbers. The effects of post HCT immunosuppression, total body
      irradiation, donor leucocyte infusions, T cell dose and post HCT infections on T
      cell recovery were also analysed. However, no effects of these single variables
      across a variety of different age, GVHD and T cell depletion groups were
      apparent. This study suggests that future analysis of the factors affecting T
      cell reconstitution and studies aimed at reactivating the thymus through
      therapeutic intervention should be analysed in age-, GVHD- and TCD-matched
      patient groups.

PMID- 14595389
TI  - Prolonged red cell aplasia after major ABO-incompatible allogeneic hematopoietic
      stem cell transplantation: removal of persisting isohemagglutinins with Ig
      Therasorb immunoadsorption.
AB  - Delayed donor red cell engraftment and prolonged red cell aplasia (PRCA) are well
      recognized complications of major ABO-incompatible myeloablative and non
      myeloablative hematopoietic stem cell transplantation (HSCT). There is an intense
      debate about the impact on outcome, severity of hemolysis, association with graft
      versus-host disease and survival after blood group-incompatible stem cell
      transplantation. Therefore, therapeutic strategies should be considered to avoid
      these possible complications. We present five patients, who received allogeneic
      HSCT from human leukocyte antigen-identical donors for hematological
      malignancies, which were treated with Ig-Therasorb immunoadsorption (five
      treatments/week) to remove persisting incompatible isohemagglutinins. After a
      median of 17 treatments (range 9-25), all the patients became transfusion
      independent with the presentation of donor's blood group. No side effects
      occurred during treatment. Ig-Therasorb immunoadsorption seems to be a promising
      therapeutic method for rapid, efficient and safe elimination for persisting
      isohemagglutinins for patients with PRCA after allogeneic hematological stem cell
      transplantation.

PMID- 14595390
TI  - Effects of incubation temperature and time after thawing on viability assessment
      of peripheral hematopoietic progenitor cells cryopreserved for transplantation.
AB  - Three widely used viability assessments were compared: (1) membrane integrity of
      nucleated cells using trypan blue (TB) exclusion and a fluorometric membrane
      integrity assay (SYTO 13 and propidium iodide), (2) enumeration of viable CD34+
      cells, and (3) clonogenic assay (granulocyte-macrophage colony-forming units, CFU
      GM). Post thaw peripheral hematopoietic progenitor cells (HPC) were incubated at
      0, 22, and 37 degrees C for 20-min intervals before assessment. The recovery of
      viable nucleated cells assessed by TB and SYTO/PI decreased significantly with
      time at incubation temperatures of 22 and 37 degrees C (P<0.05), and correlated
      with the concentration of mononuclear cells (MNC) (r=0.936, P<0.05). The decrease
      in recovery of viable nucleated cells was slower when thawed cells were incubated
      at 0 degrees C compared with 22 degrees C or 37 degrees C. The recovery, measured
      by absolute viable CD34+ or CFU-GM, was not affected by 2 h post thaw incubation
      (P>0.05) at 0, 22, and 37 degrees C (P>0.05). There were no significant
      differences in the measured recovery of viable CD34+ cells and CFU-GM at all
      incubation times (P>0.05) and temperatures (P>0.05). Both CFU-GM and absolute
      CD34+ cells can be used as post thaw viability assays for HPC cryopreserved for
      transplantation.

PMID- 14595391
TI  - Nonlethal transfusion associated graft-versus-host disease in a severe combined
      immunodeficient patient.
AB  - An X-linked severe combined immunodeficient (SCID) patient received a
      nonirradiated erythrocyte transfusion and developed transfusion-associated graft
      versus-host disease (TAGVHD), which was controllable with high-dose
      corticosteroids. Haplo-identical SCT was performed, after a myeloablative
      conditioning regimen. At day +26, he developed GVHD. Chimerism studies revealed
      DNA of the erythrocyte transfusion donor (ETD) and recipient only. Because of
      early nonengraftment and the presence of alloreactive T cells of ETD origin, the
      patient was treated with an immunosuppressive conditioning regimen followed by a
      second SCT from the same donor. While tapering immunosuppression, he again
      developed mild GVHD, and DNA of ETD and bone marrow donor origin were both
      present. On cyclosporin, the ETD-DNA signal finally disappeared. High-resolution
      HLA typing revealed haplo-identity between BMD, ETD and the patient, which might
      have contributed to the relative mild course of the TAGVHD.

PMID- 14595392
TI  - CO2 laser in oral graft-versus-host disease: a pilot study.
AB  - This paper is the first to report the benefits of CO2 laser treatment for pain
      control in severe oral chronic graft-versus-host disease (GVHD). A CO2 laser
      device was used during 17 treatment sessions in four patients. The CO2 laser was
      applied over the mucosal lesions using 1 W for 2-3 s/1 mm(2). This treatment
      resulted in a consistent and significant decrease in pain, measured using a
      standard visual analogue scale. These results suggest that the CO2 laser can be
      used for the alleviation of pain in oral chronic GVHD.

PMID- 14595393
TI  - Dosing schedule of oral valacyclovir for prevention of herpes simplex virus.

PMID- 14595394
TI  - Monitoring cyclosporine using blood drawn via a central venous catheter.

PMID- 14595395
TI  - CysG structure reveals tetrapyrrole-binding features and novel regulation of
      siroheme biosynthesis.
AB  - Sulfur metabolism depends on the iron-containing porphinoid siroheme. In
      Salmonella enterica, the S-adenosyl-L-methionine (SAM)-dependent
      bismethyltransferase, dehydrogenase and ferrochelatase, CysG, synthesizes
      siroheme from uroporphyrinogen III (uro'gen III). The reactions mediated by CysG
      encompass two branchpoint intermediates in tetrapyrrole biosynthesis, diverting
      flux first from protoporphyrin IX biosynthesis and then from cobalamin (vitamin
      B(12)) biosynthesis. We determined the first structure of this multifunctional
      siroheme synthase by X-ray crystallography. CysG is a homodimeric gene fusion
      product containing two structurally independent modules: a bismethyltransferase
      and a dual-function dehydrogenase-chelatase. The methyltransferase active site is
      a deep groove with a hydrophobic patch surrounded by hydrogen bond donors. This
      asymmetric arrangement of amino acids may be important in directing substrate
      binding. Notably, our structure shows that CysG is a phosphoprotein. From
      mutational analysis of the post-translationally modified serine, we suggest a
      conserved role for phosphorylation in inhibiting dehydrogenase activity and
      modulating metabolic flux between siroheme and cobalamin pathways.

PMID- 14595396
TI  - Tom40 protein import channel binds to non-native proteins and prevents their
      aggregation.
AB  - Mitochondria contain the translocator of the outer mitochondrial membrane (TOM)
      for protein entry into the organelle, and its subunit Tom40 forms a protein
      conducting channel. Here we report the role of Tom40 in protein translocation
      across the membrane. The site-specific photocrosslinking experiment revealed that
      translocating unfolded or loosely folded precursor segments of up to 90 residues
      can be associated with Tom40. Purified Tom40 bound to non-native proteins and
      suppressed their aggregation when they are prone to aggregate. A denatured
      protein bound to the Tom40 channel blocked the protein import into mitochondria.
      These results indicate that, in contrast to the nonstick tunnel of the ribosome
      for polypeptide exit, the Tom40 channel offers an optimized environment to
      translocating non-native precursor proteins by preventing their aggregation.

PMID- 14595397
TI  - Leash in the groove mechanism of membrane fusion.
AB  - Formation of helix bundles has been proposed as a general mechanism for viral and
      cellular membrane fusion reactions. Class I viral fusion proteins, including HIV
      Env and influenza hemagglutinin (HA), form six-helix bundles in their fusogenic
      forms. The HIV Env six-helix bundle extends to the membrane proximal end of the
      protein, where it is poised to pull the fusing membranes together. In contrast,
      the HA six-helix bundle is located at the membrane distal end of the protein. It
      is followed by a C-terminal 'leash' that packs into the grooves and extends to
      the membrane proximal end of the coiled-coil. Here, we describe the ability of C
      terminal leash mutants to change conformation and induce fusion. Our data
      indicate that packing of the C-terminal leash into the grooves of the coiled-coil
      is necessary for HA to mediate the lipid mixing stage of fusion, and that
      hydrophobic membrane proximal leash residues secure this interaction. Therefore,
      HA employs a 'leash in the groove,' rather than a helix-bundle, mechanism of
      membrane fusion.

PMID- 14595398
TI  - Alterations in the BOLD fMRI signal with ageing and disease: a challenge for
      neuroimaging.

PMID- 14595399
TI  - The molecular logic of endocannabinoid signalling.

PMID- 14595400
TI  - The other side of the engram: experience-driven changes in neuronal intrinsic
      excitability.

PMID- 14595401
TI  - Monitoring of stored and available fuel by the CNS: implications for obesity.

PMID- 14595402
TI  - Axon guidance mechanisms and molecules: lessons from invertebrates.

PMID- 14595403
TI  - The long-term potential of LTP.

PMID- 14595404
TI  - LTP: perils and progress.

PMID- 14595405
TI  - Quasi-collective motion of nanoscale metal strings in metal surfaces.
AB  - Mass transport processes on metal surfaces play a key role in epitaxial growth
      and coarsening processes. They are usually described in terms of independent,
      statistical diffusion and attachment/detachment of individual metal adatoms or
      vacancies. Here we present high-speed scanning tunnelling microscopy (video-STM)
      observations of the dynamic behaviour of five-atom-wide, hexagonally ordered
      strings of Au atoms embedded in the square lattice of the Au(100)-(1x1) surface
      that reveal quasi-collective lateral motion of these strings perpendicular to as
      well as along the string direction. The perpendicular motion can be ascribed to
      small atomic displacements in the strings induced by propagating kinks, which
      also provides a mechanism for the exchange of Au atoms between the two string
      ends, required for motion in string direction. In addition, quasi-one-dimensional
      transport of Au adatoms along the string boundaries may contribute to the latter
      phenomenon according to density functional calculations.

PMID- 14595406
TI  - Laser-driven formation of a high-pressure phase in amorphous silica.
AB  - Because of its simple composition, vast availability in pure form and ease of
      processing, vitreous silica is often used as a model to study the physics of
      amorphous solids. Research in amorphous silica is also motivated by its ubiquity
      in modern technology, a prominent example being as bulk material in transmissive
      and diffractive optics for high-power laser applications such as inertial
      confinement fusion (ICF). In these applications, stability under high-fluence
      laser irradiation is a key requirement, with optical breakdown occurring when the
      fluence of the beam is higher than the laser-induced damage threshold (LIDT) of
      the material. The optical strength of polished fused silica transmissive optics
      is limited by their surface LIDT. Surface optical breakdown is accompanied by
      densification, formation of point defects, cratering, material ejection, melting
      and cracking. Through a combination of electron diffraction and infrared
      reflectance measurements we show here that synthetic vitreous silica transforms
      partially into a defective form of the high-pressure stishovite phase under high
      intensity (GW cm(-2)) laser irradiation. This phase transformation offers one
      suitable mechanism by which laser-induced damage grows catastrophically once
      initiated, thereby dramatically shortening the service lifetime of optics used
      for high-power photonics.

PMID- 14595407
TI  - Nitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human
      circulation.
AB  - Nitrite anions comprise the largest vascular storage pool of nitric oxide (NO),
      provided that physiological mechanisms exist to reduce nitrite to NO. We
      evaluated the vasodilator properties and mechanisms for bioactivation of nitrite
      in the human forearm. Nitrite infusions of 36 and 0.36 micromol/min into the
      forearm brachial artery resulted in supra- and near-physiologic intravascular
      nitrite concentrations, respectively, and increased forearm blood flow before and
      during exercise, with or without NO synthase inhibition. Nitrite infusions were
      associated with rapid formation of erythrocyte iron-nitrosylated hemoglobin and,
      to a lesser extent, S-nitroso-hemoglobin. NO-modified hemoglobin formation was
      inversely proportional to oxyhemoglobin saturation. Vasodilation of rat aortic
      rings and formation of both NO gas and NO-modified hemoglobin resulted from the
      nitrite reductase activity of deoxyhemoglobin and deoxygenated erythrocytes. This
      finding links tissue hypoxia, hemoglobin allostery and nitrite bioactivation.
      These results suggest that nitrite represents a major bioavailable pool of NO,
      and describe a new physiological function for hemoglobin as a nitrite reductase,
      potentially contributing to hypoxic vasodilation.

PMID- 14595409
TI  - NIH at a crossroads.

PMID- 14595410
TI  - New NIH project could be road to ruin for basic research.

PMID- 14595408
TI  - Autoantibodies against cardiac troponin I are responsible for dilated
      cardiomyopathy in PD-1-deficient mice.
AB  - We recently reported that mice deficient in the programmed cell death-1 (PD-1)
      immunoinhibitory coreceptor develop autoimmune dilated cardiomyopathy (DCM), with
      production of high-titer autoantibodies against a heart-specific, 30-kDa protein.
      In this study, we purified the 30-kDa protein from heart extract and identified
      it as cardiac troponin I (cTnI), encoded by a gene in which mutations can cause
      familial hypertrophic cardiomyopathy (HCM). Administration of monoclonal
      antibodies to cTnI induced dilatation and dysfunction of hearts in wild-type
      mice. Monoclonal antibodies to cTnI stained the surface of cardiomyocytes and
      augmented the voltage-dependent L-type Ca2+ current of normal cardiomyocytes.
      These findings suggest that antibodies to cTnI induce heart dysfunction and
      dilatation by chronic stimulation of Ca2+ influx in cardiomyocytes.

PMID- 14595411
TI  - Taiwanese scientists find genetic link to SARS.

PMID- 14595412
TI  - Fear flows as efforts to ease blood shortage continue in vein.

PMID- 14595413
TI  - European researchers up in arms over new clinical trials edict.

PMID- 14595414
TI  - Scientists closing in on true identity of the 'great imitator'.

PMID- 14595415
TI  - Japanese scientists plan MMR alternative.

PMID- 14595416
TI  - WHO adopts bold plan for AIDS drug distribution.

PMID- 14595417
TI  - Patrick Brown.

PMID- 14595418
TI  - The color of money.

PMID- 14595419
TI  - World Bank meeting concludes drug resistance should not prevent distribution of
      antiretroviral therapy to poor countries.

PMID- 14595420
TI  - AIDS: doing the right thing.

PMID- 14595422
TI  - Muscles flex, axons die.

PMID- 14595423
TI  - Setting fat on fire.

PMID- 14595424
TI  - Macrophages eyed in macular degeneration.

PMID- 14595425
TI  - A TUG on glucose transport.

PMID- 14595426
TI  - Breaking the pain barrier.

PMID- 14595427
TI  - Cancer vaccine targets leukemia.

PMID- 14595429
TI  - Life on the inside for Mycobacterium tuberculosis.

PMID- 14595431
TI  - Gradual adaptation of HIV to human host populations: good or bad news?
AB  - The continuous evolution and adaptation of HIV to its host has produced extensive
      global viral diversity. Understanding the kinetics and directions of this
      continuing adaptation and its impact on viral fitness, immunogenicity and
      pathogenicity will be crucial to the successful design of effective HIV vaccines.
      Here we discuss some potential scenarios of viral and host coevolution.

PMID- 14595437
TI  - Active recruitment of DNA methyltransferases regulates interleukin 4 in
      thymocytes and T cells.
AB  - How T cells regulate interleukin 4 (IL-4) expression is not completely
      understood. We show here that single-positive thymocytes express IL-4, but
      attenuate GATA-3 expression, recruit DNA methyltransferases (Dnmts) to the Il4
      Il13 locus and downregulate IL-4 expression as they mature into T cells. Type 2
      polarization blocks Dnmt1 recruitment, enhances histone H3 Lys4 methylation
      (indicative of accessible chromatin) and initiates DNA demethylation of the
      locus. Dnmt1-/- CD4 and CD8 T cells derepress IL-4 expression considerably,
      demethylate DNA and increase H3 Lys4 methylation without affecting GATA-3
      expression, demonstrating that Dnmt1 and DNA methylation are essential for proper
      Il4 regulation. These results indicate that Dnmts, DNA and histone methylation,
      and transcription factors 'collaborate' to determine appropriate Il4 expression
      patterns.

PMID- 14595438
TI  - Mast cell-derived tumor necrosis factor induces hypertrophy of draining lymph
      nodes during infection.
AB  - Palpable swelling of regional lymph nodes is a common sequela of microbial
      infections but the mechanism responsible for the sequestration and subsequent
      coordination of lymphocyte responses within these dynamic structures remains
      poorly understood. Here we show that draining lymph nodes of mast cell-deficient
      mice did not demonstrate swelling after intradermal bacterial challenge. Testing
      of individual mast cell-derived products in this model indicated that tumor
      necrosis factor was the main mediator of nodal hypertrophy, whereas tryptase and
      histamine had no effect. After peripheral mast cell activation, both tumor
      necrosis factor concentrations and the recruitment of circulating T cells were
      increased within draining nodes. These results show a critical function for
      peripheral mast cell-derived tumor necrosis factor in regulating the hypertrophy
      of draining lymph nodes during infection.

PMID- 14595439
TI  - Variable MHC class I engagement by Ly49 natural killer cell receptors
      demonstrated by the crystal structure of Ly49C bound to H-2K(b).
AB  - The Ly49 family of natural killer (NK) receptors regulates NK cell function by
      sensing major histocompatibility complex (MHC) class I. Ly49 receptors show
      complex patterns of MHC class I cross-reactivity and, in certain cases, peptide
      selectivity. To investigate whether specificity differences result from
      topological differences in MHC class I engagement, we determined the structure of
      the peptide-selective receptor Ly49C in complex with H-2K(b). The Ly49C homodimer
      binds two MHC class I molecules in symmetrical way, a mode distinct from that of
      Ly49A, which binds MHC class I asymmetrically. Ly49C does not directly contact
      the MHC-bound peptide. In addition, MHC crosslinking by Ly49C was demonstrated in
      solution. We propose a dynamic model for Ly49-MHC class I interactions involving
      conformational changes in the receptor, whereby variations in Ly49 dimerization
      mediate different MHC-binding modes.

PMID- 14595440
TI  - Pyruvate kinase deficiency in mice protects against malaria.
AB  - The global health impact of malaria is enormous, with an estimated 300-500
      million clinical cases and 1 million annual deaths. In humans, initial
      susceptibility to infection with Plasmodium species, disease severity and
      ultimate outcome of malaria (self-healing or lethal) are under complex genetic
      control. Alleles associated with sickle cell anemia, beta-thalassemia and
      deficiency in glucose-6-phosphate dehydrogenase have a protective effect against
      malaria and may have been retained by positive selection in areas of endemic
      malaria. Likewise, genetic variations in erythrocyte antigens and levels of host
      cytokines affect type and severity of disease. A mouse model of infection with
      Plasmodium chabaudi was used to study the genetic component of malaria
      susceptibility. Segregation analyses in informative F2 crosses derived from
      resistant C57BL/6J and susceptible A/J, C3H and SJL strains using extent of blood
      stage replication of the parasite and survival as traits mapped three P. chabaudi
      resistance (Char) loci on chromosomes 9 (Char1), 8 (Char2) and 17 (Char3, MHC
      linked). Recombinant congenic strains AcB55 and AcB61 are unusually resistant to
      malaria despite carrying susceptibility alleles at Char1 and Char2. Malaria
      resistance in AcB55 and AcB61 is associated with splenomegaly and constitutive
      reticulocytosis, is inherited in an autosomal recessive fashion and is controlled
      by a locus on chromosome 3 (Char4). Sequencing of candidate genes from the Char4
      region identified a loss-of-function mutation (269T-->A, resulting in the amino
      acid substitution I90N) in the pyruvate kinase gene (Pklr) that underlies the
      malaria resistance in AcB55 and AcB61. These results suggest that pyruvate kinase
      deficiency may similarly protect humans against malaria.

PMID- 14595442
TI  - Contextual tuning of direction-selective retinal ganglion cells.
AB  - A direction-selective (DS) retinal ganglion cell responds well to a small object
      moving within its receptive field center, but less well when there is also a
      moving stimulus in the surrounding area; this has been described as tuning for
      local motion. We show here an additional selectivity, such that the surround has
      less effect if there is a discontinuity--that is, a difference in spatial phase,
      spatial frequency or velocity--between the center stimulus and that present in
      the surround.

PMID- 14595441
TI  - Heterozygous mutations of the kinesin KIF21A in congenital fibrosis of the
      extraocular muscles type 1 (CFEOM1).
AB  - Congenital fibrosis of the extraocular muscles type 1 (CFEOM1; OMIM #135700) is
      an autosomal dominant strabismus disorder associated with defects of the
      oculomotor nerve. We show that individuals with CFEOM1 harbor heterozygous
      missense mutations in a kinesin motor protein encoded by KIF21A. We identified
      six different mutations in 44 of 45 probands. The primary mutational hotspots are
      in the stalk domain, highlighting an important new role for KIF21A and its stalk
      in the formation of the oculomotor axis.

PMID- 14595443
TI  - The netrin-G1 ligand NGL-1 promotes the outgrowth of thalamocortical axons.
AB  - Netrin-G1 is a lipid-anchored protein that is structurally related to the netrin
      family of axon guidance molecules. Netrin-G1 does not bind any of the known
      netrin receptors and its function is not known. Here we identify human netrin-G1
      ligand (NGL-1), a transmembrane protein containing leucine-rich repeat (LRR) and
      immunoglobulin (Ig) domains that specifically interacts with netrin-G1 through
      its LRR region. Whereas netrin-G1 is expressed highly in mouse thalamic axons,
      NGL-1 is most abundant in the striatum and the cerebral cortex--the intermediate
      and final targets, respectively, of thalamocortical axons (TCAs). Surface-bound
      NGL-1 stimulates, but soluble NGL-1 disrupts, the growth of embryonic thalamic
      axons, and in vitro data indicate that NGL-1 activity may be mediated at least
      partially by netrin-G1. Our findings provide evidence that netrin-G1 functions as
      an important component of the NGL-1 receptor to promote TCA outgrowth and that
      membrane-bound netrins can participate in receiving axonal signaling pathways.

PMID- 14595445
TI  - Prevalence of Helicobacter pylori infection in Warao lineage communities of Delta
      Amacuro State, Venezuela.
AB  - The purpose of this study was the evaluation of Helicobacter pylori infections in
      children and adults from two indigenous communities of Delta Amacuro State,
      Venezuela, that differ in hygienic conditions of the housing. The evaluation was
      performed in 98 children (mean age 7 +/- 3.37 years) and their mothers (33.96 +/-
      13.77 years) from two communities of Warao lineage. Anti-H. pylori serum IgG and
      secretory anti-H. pylori IgA antibodies were determined, as well as total
      secretory IgA and H. pylori antigens in feces. Serological prevalence of H.
      pylori infection was 38% in children and 84% their in mothers. Children from the
      community that had the most deficient sanitary and hygienic conditions had
      significantly lower titers of specific IgG antibodies and total secretory IgA
      (P<0.0001) and a high percentage of them had H. pylori antigens in their feces
      (P<0.0001). The levels of specific IgA were similar in both groups. The results
      indicate that in these populations there is a high prevalence of H. pylori
      infection and that poor hygienic conditions can increase the risk of infection
      and damage to the gastrointestinal tract.

PMID- 14595447
TI  - Horizontal stratification of the sand fly fauna (Diptera: Psychodidae) in a
      transitional vegetation between caatinga and tropical rain forest, state of
      Bahia, Brazil.
AB  - A study about the horizontal stratification of the sand fly fauna in two distinct
      ecosystems, caatinga area, endemic for visceral leishmaniasis, and the tropical
      rain forest area, endemic for cutaneous leishmaniasis, was performed in the state
      of Bahia, Brazil. Lutzomyia longipalpis was predominant in the caatinga, and
      following it came the species L. capixaba and L. oswaldoi. In the tropical rain
      forest other species were found, such as L. intermedia, L. migonei, L. whitmani,
      L. yuilli, L.fischeri, L. damascenoi, L. evandroi, L. monticola, and L. lenti. It
      was found that the geographical limits of the vector species of visceral and
      cutaneous leishmaniasis are clearly defined by the biological and phytogeographic
      characteristics.

PMID- 14595446
TI  - Prevalence of infection with hantavirus in rodent populations of central
      Argentina.
AB  - We studied hantavirus seroprevalence and virus variability in rodent populations
      in Diego Gaynor, northwest of Buenos Aires province, Argentina. Rodent samplings
      were conducted in railroads and cropfield borders in March and July 1999,
      September and December 2000, and March 2001. Antibody detection was performed by
      an enzyme link immunosorbent assay (ELISA), using the recombinant nucleoprotein
      of Andes (AND) virus as antigen. Tissue samples were taken from positive antibody
      individuals in order to confirm the presence of hantavirus genomic material and
      to identify virus genotypes. Akodon azarae was the most abundant species,
      followed by Oligoryzomys flavescens, while Calomys laucha and C. musculinus were
      rarely caught. We found a rate of seroprevalence of 9.3% for a total sample of
      291 A. azarae and 13.5% for 37 O. flavescens. After molecular analyses of
      hantavirus, we confirmed the presence of hantavirus genomic material in 16
      individuals with ELISA (+) results and two individuals with ELISA (-). Four
      amplimers for each species were sequenced and compared to the corresponding
      sequences of representative hantaviruses. We identified the AND Cent Lec from
      three O. flavescens, and the Pergamino virus from four A. azarae and from one O.
      flavescens. A. azarae males had higher seroprevalence than females, and heavier
      individuals showed higher seroprevalence than lighter ones. We did not find
      seroprevalence differences according to sex in O. flavescens, although this
      result may have been produced by the low sample size. The lowest seroprevalence
      was found in a period of high rodent density, when juveniles prevailed in the
      population. We found higher seroprevalences than those detected in previous
      studies for other localities of central Argentina where cases of hantavirus
      pulmonary syndrome (HPS) have been reported. The presence of AND Cent Lec virus
      in rodent populations of the study area, which is responsible of HPS cases in
      central Argentina, suggests that human populations are at risk of HPS disease,
      although there were not reported cases of this disease until today.

PMID- 14595448
TI  - Respiratory syncytial virus infections during an epidemic period in Salvador,
      Brazil. Viral antigenic group analysis and description of clinical and
      epidemiological aspects.
AB  - Acute respiratory infections (ARI) caused by respiratory syncytial virus (RSV)
      were studied in 482 children from Salvador, BA, Brazil, over a period of 12
      months. The epidemic period of RSV infections in Salvador occurred from February
      (summer) to August (winter), with peaks in May, June, and July. The grouping
      characteristics of 84 RSV present in nasopharyngeal secretions of children seen
      at a reference university hospital were analyzed. RSV represented 17.4% of all
      cases and 54.5% of the positive samples. Sixty-four RSV strains were assigned to
      group A and 14 to group B. Both groups circulated in the five months of the
      epidemic period studied. Infections by both groups of RSV were more frequent in
      children up to one year of age. The incidence of RSV ARI was slightly more
      frequent in males, although group B had more infected females.

PMID- 14595449
TI  - Acute schistosomiasis outbreak in the metropolitan area of Belo Horizonte, Minas
      Gerais: alert about the risk of unnoticed transmission increased by growing rural
      tourism.
AB  - The present article describes the occurrence of 17 cases of acute schistosomiasis
      in the metropolitan area of Belo Horizonte, state of Minas Gerais, Brazil. All
      individuals affected took a bath in a swimming pool of a holiday resort that was
      provided with water from a nearby brook. The apparently clean water and the
      absence of snails in the pool gave the wrong impression that there was no risk
      for infection. During a malacological survey at the site snails of the species
      Biomphalaria glabrata were found and tested positive for Schistosoma mansoni. All
      the patients live in the middle-class area of Barreiro, metropolitan area of Belo
      Horizonte and have medium grade school education. The difficulties in
      establishing the right diagnosis is expressed by the search for medical attention
      in 17 different medical facilities, the wide range of laboratory test and the
      inadequate treatment administration. A lack of knowledge about the disease was
      found in all groups studied. The booming rural tourism in endemic areas is
      identified as a probable risk factor for infection, especially for individuals of
      the non-immune middle and upper class parts of the society in urban centers.
      Special attention is given to a multidisciplinary approach to the complex issue
      of disease control and prevention.

PMID- 14595451
TI  - The subgenus Scaptia (Lepmia) Fairchild: redescription of females and description
      of a male (Diptera: Tabanidae: Pangoniinae).
AB  - The subgenus Scaptia (Lepmia) Fairchild, known only from mountainous areas of
      Southeast of Brazil, is redescribed and illustrated. It is contrasted with
      similar species of Scaptia (Pseudoscione). It is more similar to the Australian
      Myioscaptia and Plinthina than to the other New World Scaptia subgenera.

PMID- 14595450
TI  - Recent observations on the sand fly (Diptera: Psychodidae) fauna of the State of
      Rondonia, Western Amazonia, Brazil: the importance of Psychdopygus davisi as a
      vector of zoonotic cutaneous leishmaniasis.
AB  - Sand flies were collected in the central region of the state of Rondonia (W 64
      degrees 30' to 63 degrees 00' and S 10 degrees 00'to 11 degrees 00') using
      Shannon and CDC light traps from October 1997 to August 2000. A total of 85,850
      specimens representing 78 named species were captured. Of these 14 were new
      records for Rondonia. The proportion of males/females was 1/1.131.
      Trypanosomatids, that are presently being identified, were detected in 11
      species. Leishmania (Viannia) naiffi was recorded from Psychodopygus davisi and
      P. hirsutus. In the present study the dominant species was P. davisi (39.6%)
      followed by Lutzomyia whitmani (13.1%), P. carrerai (11.6%), and P. hirsutus
      (10.2%). The importance of P. davisi as a vector of zoonotic cutaneous
      leishmaniasis is discussed.

PMID- 14595452
TI  - A new species of Henneguya, a gill parasite of Astyanax altiparanae (Pisces:
      Characidae) from Brazil, with comments on histopathology and seasonality.
AB  - A new species of Myxosporea, Henneguya chydadea, is described parasitizing the
      gills of Astyanax altiparanae collected from a lake on Rio das Pedras farm near
      Campinas, state of Sao Paulo, Brazil. Of the fish examined, 88.3% had gills
      parasitized by myxosporeans. The prevalence of the parasite ranged from 80% in
      the spring and fall, 93% in the summer and 100% in the winter. The parasite
      induced the formation of white, oval-shaped cysts measuring 40-64 microm x 64-80
      microm which deformed the gill lamellae, compressed the capillaries, and caused
      retraction of the neighboring lamellae. The mature spores were elongated and had
      two identical, parallel elongate polar capsules. Each capsule contained a polar
      filament with 9-10 turns. There was no mucous envelope or iodinophilous vacuole.
      Morphometric differences between this parasite and other species of the genus
      Henneguya indicated, that the parasite observed in A. altiparanae is a new
      species. This is the first report of a myxosporeanparasitizing A. altiparanae.

PMID- 14595453
TI  - Planorbidae, lymnaeidae and physidae of Peru (Mollusca: Basommatophora).
AB  - In the course of several trips to Peru I had the opportunity of collecting
      topotypic specimens of Biomphalaria andecola (Orbigny, 1835), B. helophila
      (Orbigny, 1835), B. pucaraensis (Preston, 1909), Drepanotrema limayanum (Lesson,
      1830), D. kermatoides (Orbigny, 1835), and Lymnaea viatrix Orbigny, 1835, besides
      B. tenagophila (Orbigny, 1835), Helisoma trivolvis (Say, 1817), H. duryi
      (Wetherby, 1879), Physa acuta Draparnaud, 1801, and seemingly P. peruviana Gray,
      1828. B. pucaraensis is considered a junior synonym of B. peregrina (Orbigny,
      1835).

PMID- 14595454
TI  - Glandular areas associated with the male genitalia in Triatoma rubrofasciata
      (Triatominae, Reduviidae, Hemiptera) and other Reduviidae.
AB  - In this paper, glandular areas associated with the phallus in Triatoma
      rubrofasciata are described and illustrated for the first time. The glandular
      areas lie in the membrane surrounding the articulatory apparatus. In order to
      unambiguously define the locality of the respective glandular areas, some
      features of the pygophore-phallus connection are redescribed. A possible
      functional context of the gland secretions is discussed. A preliminary study of
      several other Reduviidae implies that the described glandular areas occur in a
      wider range of taxa in this group.

PMID- 14595455
TI  - Development of genital plates in nymphs of Triatoma pallidipennis, Stal 1872,
      (Hemiptera: Reduviidae) and its application as sexing method.
AB  - Searching for morphometric differences between sexes in immature forms, the
      development of genital plates in the exuviae of Triatoma pallidipennis Stal 1872
      nymphs was studied. Differences were found in the form and size of the 9th
      genital urosternite, it is larger and wider in males as compared to females. This
      difference is reported in several South American Triatoma species. From our
      results it is possible to sex early stages from microscopic observation of
      genital plates in whole insects.

PMID- 14595456
TI  - A comparative parasitologic study on Biomphalaria glabrata snail and C3H/He mice
      infected with human and murine isolates of Schistosoma mansoni derived from
      Sumidouro, Rio de Janeiro, Brazil.
AB  - Experiments were carried out to analyze the biological characteristics of two
      sympatric isolates of Schistosoma mansoni derived from humans and murines in a
      low endemic transmission area (Sumidouro county, state of Rio de Janeiro,
      Brazil). Sympatric reared-laboratory Biomphalaria glabrata and C3H/He mice were
      used as experimental hosts. Parameters assessed comprised: precercarial period,
      infectivity and mortality (snails), prepatent period, infectivity (percentage of
      cercariae maturation into adult worm) and intestinal egg count (mice). The murine
      isolate showed a shorter precercarial period and higher infectivity than human
      isolate (p<0.05). This biological heterogenicity did not correspond to the
      vertebrate data because any biological parameter presented significant difference
      (p>0.05). These data suggest that both isolates are local sub-populations,
      providing support for the hypotheses that in a same biotope mixed populations or
      sub-populations circulate among their main host (human beings) and/or rodent as
      an anfixenous infection.

PMID- 14595457
TI  - The role of urea in the oviposition behaviour of Japanese encephalitis vectors in
      rice fields of South India.
AB  - The effect of urea on the oviposition behaviour of culicine vectors of Japanese
      encephalitis was studied in rice fields. Gravid females had a strong preference
      for oviposition in urea treated areas in rice fields, while no such preference
      was exhibited in untreated areas. The egg laying declined in the area where urea
      treated water surface had a mechanical barrier, which allowed volatile fractions
      to escape, but prevented contact with the water. Urea was shown to act as an
      oviposition attractant/stimulant for Culex tritaeniorhynchus, but its role was
      not clear for Cx. vishnui, as the number of egg rafts obtained for the latter
      species was low.

PMID- 14595459
TI  - Trichomycetes (Zygomycota) in the digestive tract of arthropods in Amazonas,
      Brazil.
AB  - Eight species of Harpellales and three species of Eccrinales (Zygomycota:
      Trichomycetes) were found associated with the digestive tract of arthropods from
      terrestrial and aquatic environments in the central Amazon region of Brazil. New
      species of Harpellales include: Harpella amazonica, Smittium brasiliense,
      Genistellospora tropicalis in Simuliidae larvae and Stachylina paucispora in
      Chironomidae larvae. Axenic cultures of S. brasiliense were obtained. Probable
      new species of Enterobryus (Eccrinales), Harpella, and Stachylina (Harpellales)
      are described but not named. Also reported are the previously known species of
      Eccrinales, Passalomyces compressus and Leidyomyces attenuatus in adult
      Coleoptera (Passalidae), and Smittium culisetae and Smittium aciculare
      (Harpellales) in Culicidae and Simuliidae larvae, respectively. Comments on the
      distribution of some of these fungi and their hosts in the Neotropics are
      provided.

PMID- 14595458
TI  - Host-ectoparasite specificity in a small mammal community in an area of Atlantic
      Rain Forest (Ilha Grande, State of Rio de Janeiro), Southeastern Brazil.
AB  - The analyses of the ectoparasite species associated with a small mammal community
      on Ilha Grande, a coastal island in southern of the state of Rio de Janeiro,
      Brazil, evaluated the level of host-ectoparasite specificity. Was used the
      Jaccard index for qualitative data to analyse the similarity. The lowest value of
      similarity occurred between Proechimys iheringi and Marmosops incanus and between
      Sciurus aestuans and Nectomys squamipes (Cj=0.08) and the highest between P.
      iheringi and Oxymycterus sp. (Cj=0.33). This index showed a low value of
      similarity across the ectoparasite community. The only exception from this
      pattern of high host specificity occurred with P. iheringi and Oxymycterus sp.,
      which shared five species of ectoparasites. The similarity values, for most of
      the cases, is smaller than 0.2.

PMID- 14595460
TI  - Host characteristics do not affect community structure of ectoparasites on the
      fishing bat Noctilio leporinus (L., 1758) (Mammalia: Chiroptera).
AB  - Patterns of parasite abundance and prevalence are thought to be influenced by
      several host characteristics such as size, sex, developmental stage, and
      seasonality. We examined two obligatory ectoparasites of the bat Noctilio
      leporinus (L.) (Chiroptera, Noctilionidae) to test whether prevalence and
      abundance of Noctiliostrebla aitkeni Wenzel and Paradyschiria fusca Speiser
      (Diptera, Streblidae) are influenced by the host characteristics. During this
      survey, 2110 flies were collected. The total abundance was 1150 N. aitkeni and
      950 P. fusca. The prevalence of both species was shown to be superior to 75% and
      neither host size, sex, reproductive stage nor season influenced significantly
      the variation of the observed values. N. aitkeni were more abundant than P. fusca
      in all seasons except winter. Both flies showed a significant seasonal variation
      in terms of abundance but host biological characteristics (host size, sex, and
      reproductive stage) did not play a significant role as structuring factors of the
      batflies component community.

PMID- 14595461
TI  - Prevalence of cagA and vacA genes in isolates from patients with Helicobacter
      pylori-associated gastroduodenal diseases in Recife, Pernambuco, Brazil.
AB  - Geographical differences in the prevalence of Helicobacter pylori genes and their
      association with disease severity have been identified. This study analyzes the
      prevalences of the cagA gene and alleles of the vacA gene in H. pylori-associated
      gastroduodenal diseases in isolates from Recife, PE, Brazil. Gastric biopsy of 61
      H. pylori-positive patients were submitted to DNA extraction and gene
      amplification by polymerase chain reaction. Among the 61 patients, 21 suffered
      from duodenal ulcer (DU) and 40 from gastritis (GT). The prevalence of H. pylori
      strains harbouring the cagA gene was higher in the DU group (90.5%) than in the
      GT group (60%) (p=0.02). The vacA gene was amplified in 56 out of 61 biopsies, of
      which 43 (76.8%) contained bacteria carrying the s1 allele and 13 (23.2%) the s2.
      However, the prevalence of the vacA s1 genotyping was the same in either DU or GT
      group. The majority of the s1-typed strains, 39 (90.7%) out of 43, were subtype
      s1b. In resume there was a strong association between the H. pylori cagA+ gene
      and DU. However, there were no differences between the DU and GT groups in
      relation to the vacA s1 and s2 alleles distribution, albeit the subtype s1b was
      predominant.

PMID- 14595462
TI  - Antibody isotype responses in Balb/c mice immunized with the cytoplasmic
      repetitive antigen and flagellar repetitive antigen of Trypanosoma cruzi.
AB  - In the present report we analyzed the levels of IgG1, IgG2a, IgG2b and IgG3
      isotypes from Balb/c mice immunized with cytoplasmic repetitive antigen (CRA),
      and flagellar repetitive antigen (FRA) of Trypanosoma cruzi. The immunization was
      done by subcutaneous route three times (20 days apart) and the analysis was
      performed 14 days after each treatment. CRA-immunized mice produced high levels
      of all IgG isotypes, mainly IgG3 and IgG1. FRA-immunization elicited only high
      levels of IgG1.

PMID- 14595463
TI  - Evaluation of indirect susceptibility testing of Mycobacterium tuberculosis to
      the first- and second-line, and alternative drugs by the newer MB/BacT system.
AB  - In order to evaluate the Organon Teknika MB/BacT system used for testing indirect
      susceptibility to the alternative drugs ofloxacin (OFLO), amikacin (AMI), and
      rifabutin (RIF), and to the usual drugs of standard treatment regimes such as
      rifampin (RMP), isoniazid (INH), pyrazinamide (PZA), streptomycin (SM),
      ethambutol (EMB), and ethionamide (ETH), cultures of clinical specimens from 117
      patients with pulmonary tuberculosis under multidrug-resistant investigation,
      admitted sequentially for examination from 2001 to 2002, were studied. Fifty of
      the Mycobacterium tuberculosis cultures were inoculated into the gold-standard
      BACTEC 460 TB (Becton Dickinson) for studying resistance to AMI, RIF, and OFLO,
      and the remaining 67 were inoculated into Lowenstein Jensen (LJ) medium (the gold
      standard currently used in Brazil) for studying resistance to RMP, INH, PZA, SM,
      EMB, and ETH. We observed 100% sensitivity for AMI (80.8-100), RIF (80.8-100),
      and OFLO (78.1-100); and 100% specificity for AMI (85.4-100), RIF (85.4-100), and
      OFLO (86.7-100) compared to the BACTEC system. Comparing the results obtained in
      LJ we observed 100% sensitivity for RMP (80-100), followed by INH-95% (81.8
      99.1), EMB-94.7% (71.9-99.7), and 100% specificity for all drugs tested except
      for PZA-98.3 (89.5-99.9) at 95% confidence interval. The results showed a high
      level of accuracy and demonstrated that the fully automated, non-radiometric
      MB/BacT system is indicated for routine use in susceptibility testing in public
      health laboratories.

PMID- 14595464
TI  - Human immunodeficiency virus type 1: drug resistance in treated and untreated
      Brazilian children.
AB  - Twenty-two vertically human immunodeficiency virus type 1 (HIV-1) infected
      Brazilian children were studied for antiretroviral drug resistance. They were
      separated into 2 groups according to the administration of antiretroviral therapy
      into those who presented disease symptoms or without symptoms and no therapy.
      Viral genome sequencing reactions were loaded on an automated DNA sampler
      (TruGene, Visible Genetics) and compared to a database of wild type HIV-1. In the
      former group 8 of 12 children presented isolates with mutations conferring
      resistance to protease inhibitors (PIs), 7 presented isolates resistant to
      nucleoside reverse transcriptase inhibitors (NRTIs) and 2 presented isolates
      resistant to non-nucleoside reverse transcriptase inhibitors (NNRTIs). Ten
      children were included in the antiretroviral na ve group. Eight were susceptible
      to NRTIs and all of them were susceptible to PIs; one presented the V108I
      mutation, which confers low-level resistance to NNRTIs. The data report HIV
      mutant isolates both in treated and untreated infants. However, the frequency and
      the level of drug resistance were more frequent in the group receiving
      antiretroviral therapy, corroborating the concept of selective pressure acting on
      the emergence of resistant viral strains. The children who presented alterations
      at polymorphism sites should be monitored for the development of additional
      mutations occurring at relevant resistance codons.

PMID- 14595465
TI  - In vitro susceptibility characteristics of Cryptococcus neoformans varieties from
      AIDS patients in Goiania, Brazil.
AB  - Sixty clinical isolates of Cryptococcus neoformans from AIDS from Goiania, state
      of Goias, Brazil, were characterized according to varieties, serotypes and tested
      for antifungal susceptibility. To differentiate the two varieties was used L
      canavanine-glycine-bromothymol blue medium and to separate the serotypes was used
      slide agglutination test with Crypto Check Iatron. The Minimal Inhibitory
      Concentration (MIC) of fluconazole, itraconazole, and amphotericin B were
      determined by the National Committee for Clinical Laboratory Standards
      macrodilution method. Our results identified 56 isolates as C. neoformans var.
      neoformans serotype A and 4 isolates as C. neoformans var. gattii serotype B. MIC
      values for C. neoformans var. gattii were higher than C. neoformans var.
      neoformans. We verified that none isolate was resistant to itraconazole and to
      amphotericin B, but one C. neoformans var. neoformans and three C. neoformans
      var. gattii isolates were resistant to fluconazole. The presence of C. neoformans
      var. gattii fluconazole resistant indicates the importance of determining not
      only the variety of C. neoformans infecting the patients but also measuring the
      MIC of the isolate in order to properly orient treatment.

PMID- 14595466
TI  - Cytotoxicity and potential antiviral evaluation of violacein produced by
      Chromobacterium violaceum.
AB  - Natural products are an inexhaustible source of compounds with promising
      pharmacological activities including antiviral action. Violacein, the major
      pigment produced by Chromobacterium violaceum, has been shown to have antibiotic,
      antitumoral and anti-Trypanosoma cruzi activities. The goal of the present work
      was to evaluate the cytotoxicity of violacein and also its potential antiviral
      properties. The cytotoxicity of violacein was investigated by three methods: cell
      morphology evaluation by inverted light microscopy and cell viability tests using
      the Trypan blue dye exclusion method and the MTT assay. The cytotoxic
      concentration values which cause destruction in 50% of the monolayer cells (CC50)
      were different depending on the sensitivity of the method. CC50 values were > or
      =2.07 +/- 0.08 microM for FRhK-4 cells: > or =2.23 +/- 0.11 microM for Vero
      cells; > or =2.54 +/- 0.18 microM for MA104 cells; and > or =2.70 +/- 0.20 microM
      for HEp-2 cells. Violacein showed no cytopathic inhibition of the following
      viruses: herpes simplex virus type 1 (HSV-1) strain 29-R/acyclovir resistant,
      hepatitis A virus (strains HM175 and HAF-203) and adenovirus type 5 nor did it
      show any antiviral activity in the MTT assay. However violacein did show a weak
      inhibition of viral replication: 1.42 +/- 0.68%, 14.48 +/- 5.06% and 21.47 +/-
      3.74% for HSV-1 (strain KOS); 5.96 +/- 2.51%, 8.75 +/- 3.08% and 17.75 +/- 5.19%
      for HSV-1 (strain ATCC/VR-733); 5.13 +/- 2.38 %, 8.18 +/- 1.11% and 8.51 +/-
      1.94% for poliovirus type 2; 8.30 +/- 4.24%; 13.33 +/- 4.66% and 24.27 +/- 2.18%
      for simian rotavirus SA11, at 0.312, 0.625 and 1.250 mM, respectively, when
      measured by the MTT assay.

PMID- 14595467
TI  - Strongyloides venezuelensis alkaline extract for the diagnosis of human
      strongyloidiasis by enzyme-linked immunosorbent assay.
AB  - The present study was conducted to detected IgG antibodies using Strongyloides
      venezuelensis alkaline extract for the diagnosis of human strongyloidiasis by the
      enzyme-linked immunosorbent assay (ELISA). Sera from 90 subjects were analyzed
      (30 with strongyloidiasis, 30 with other parasites and 30 healthy individuals).
      Results were expressed in antibody titers, which were considered as positive when
      titer was >80. Sensibility and specificity of the assay were 100% and 96.7%,
      respectively. It can be concluded that the heterologous alkaline extract could be
      employed in ELISA as a diagnostic aid in human strongyloidiasis, due to its
      advantages as easiness of obtaining, practicability in preparing, and high
      indexes of sensitivity and specificity.

PMID- 14595468
TI  - Schistosomiasis mansoni: follow-up of control program based on parasitologic and
      serologic methods in a Brazilian community of low endemicity.
AB  - A field survey on schistosomiasis was carried out in 1998, in the municipality of
      Pedro de Toledo, a low endemic area in the state of Sao Paulo, Brazil. According
      to the parasitologic Kato-Katz method, the prevalence rate was 1.6%, with an
      infection intensity of 40.9 eggs per gram of stool. By the immunofluorescence
      test (IFT) for detection of IgG and IgM antibodies in the serum, IgG-IFT and IgM
      IFT, respectively, prevalence indices of 33.2% and 33.5% were observed. To assess
      the impact of the schistosomiasis control program in the area, parasitologic and
      serologic data obtained in 1998, analyzed according to the age, sex, and
      residence zone, were compared to previous data obtained in a epidemiologic study
      carried out in 1980, when prevalence indices were of 22.8% and 55.5%,
      respectively by Kato-Katz and IgG-IFT. A significant fall of the prevalence was
      observed, indicating that the control measures were effective. Nonetheless,
      residual transmission was observed, demonstrating the need for a joint effort to
      include new approaches for better understanding the real situation and improving
      the control of the disease in low endemic areas.

PMID- 14595469
TI  - Analysis of parahippocampal gyrus in 115 patients with hippocampal sclerosis.
AB  - PURPOSE: Analysis of the parahippocampal gyrus (PHG) involvement in 115 patients
      with hippocampal sclerosis (HS) by MR imaging. The simultaneous occurrence of
      ipsilateral fornix (F) and mamillary body (MB) volume loss was checked also.
      These findings were correlated with the side of hippocampal involvement, the sex,
      patient s age, and the symptoms onset. METHOD: The MR images of 115 patients with
      HS were studied retrospectively. All the examinations were performed on 1.5 T
      units (SIGNA, GE, Milwaukee, WI) and included high resolution coronal T2-weighted
      images (3 mm thickness, 0.6 mm gap). RESULTS: The patient's age ranged between
      3.5 and 80 years (mean 34.1); 62 (53.9%) were female and 53 (46.1%) were male.
      There were HS on the left side in 53 (46.0%), on the right side in 51 (44.3%),
      and bilateral in 11 (9.7%). In 43 (37.3%) cases there were ipsilateral PHG volume
      loss and signal hyper intensity on T2-weighted imaging. In 29 (25.2%) cases there
      were ipsilateral fornix volume loss and in 10 (34.5%) of this there were also
      ipsilateral MB changes. In abnormal PHG, 23 (53.4%) were on the left side, 17
      (39.5%) were on the right side, and 3 (7.1%) were bilateral. There were fornix
      changes in 15 (34.8%) cases and MB volume loss in 5 (11.6%) cases. Pertinent
      clinical data were obtained in only 18 (41.8%) of the PHG lesion cases and 11
      (61.1%) of these patients had epileptic attacks for more than 20 years before the
      examination. CONCLUSION: PHG involvement must be investigated in patients with HS
      and we suggest that the term mesial temporal sclerosis should be used only if
      there are also changes at this anatomical site.

PMID- 14595470
TI  - Neurocortical electrical activity tomography in chronic schizophrenics.
AB  - Functional imaging of brain electrical activity was performed in 25 chronic
      medicated schizophrenics and 40 controls, analyzing the classical frequency bands
      (delta, theta, alpha, and beta) of 19-channel EEG during resting state to
      identify brain regions with deviant activity of different functional
      significances, using LORETA (Low Resolution Tomography) and SPM99 (Statistical
      Parametric Mapping). Patients differed from controls due to an excess of slow
      activity comprising delta + theta frequency bands (inhibitory pattern) located at
      the right middle frontal gyrus, right inferior frontal gyrus, and right insula,
      as well as at the bilateral anterior cingulum with a left preponderance. The high
      temporal resolution of EEG enables the specification of the deviations not only
      as an excess or a deficit of brain electrical activity, but also as inhibitory
      (delta, theta), normal (alpha), and excitatory (beta) activities. These
      deviations point out to an impaired functional brain state consisting of
      inhibited frontal and prefrontal areas that may result in inadequate treatment of
      externally or internally generated information.

PMID- 14595471
TI  - Panic disorder in a breath-holding challenge test: a simple tool for a better
      diagnosis.
AB  - OBJECTIVE: Our aim was to observe if anxiety disorder patients - DSM-IV - respond
      in a similar way to the induction of panic attacks by a breath-holding challenge
      test. METHOD: We randomly selected 29 panic disorder (PD) patients, 27 social
      anxiety disorder (SAD) patients, 21 generalized anxiety disorder (GAD) patients.
      They were induced to breath-hold for as long as possible four times with two
      minute interval between them. Anxiety scales were applied before and after the
      test. RESULTS: A total of 44.8% (n=13) PD patients, 14.8% (n=4) SAD patients,
      9.5% (n=2) GAD patients had a panic attack after the test (c = 21.44, df= 2,
      p=0.001). There was no heart rate or anxiety levels difference among the groups
      before and after the test. CONCLUSION: In this breath-holding challenge test the
      panic disorder patients were more sensitive than other anxiety disorder patients.

PMID- 14595472
TI  - Restless legs syndrome in patients on chronic hemodialysis in a Brazilian city:
      frequency, biochemical findings and comorbidities.
AB  - OBJECTIVE: To evaluate the frequency of restless legs syndrome (RLS) in patients
      with chronic renal failure (CRF) in Petr polis, Brazil, and investigate
      associations between the syndrome and: demographic characteristics, biochemical
      variables and comorbidities. METHOD: A cross-sectional study in which we
      interviewed 176 patients on dialytic therapy based on criteria elaborated by the
      International Restless Legs Syndrome Study Group, and compared data of patients
      with and without RLS. RESULTS: The frequency was 14.8 %. There were no
      significant differences between the two groups in demographic and biochemical
      variables investigated (iron, creatinine, intact parathyroid hormone, hemoglobin,
      calcium, phosphate). We found no association between RLS and the most common
      comorbidities, except for chronic glomerulonephritis (CGN) (OR = 3.84, p < 0.01).
      CONCLUSION: In the studied population RLS is a common disorder, and is not
      associated with the investigated biochemical abnormalities. A higher frequency of
      RLS in subjects with CGN is a finding that needs further investigation.

PMID- 14595473
TI  - Frequency of lymphocytic meningitis associated with mumps before and after a mass
      campaign for mumps vaccination in children from Salvador, Northeast Brazil.
AB  - OBJECTIVE: To describe the frequency of lymphocytic meningitis(LM) concomitant
      with mumps, before and after the mumps mass immunization campaign in 1997.
      METHOD: Demographic, clinical and cerebrospinal fluid(CSF) information was
      collected from the chart of all patients aged from 2 to 59 months, whose CSF exam
      was performed at the CSF Lab/FJS, between 1989 and 2001. LM was defined as
      pleocytosis composed by lymphomononuclear cells and negative exams for bacterial
      or mycologic infection. RESULTS: Of 1,519 patients, 894(58.9%) had normal exams.
      LM was present in 301(19.8%) patients, out of which 22(7.3%) had concomitant
      mumps. The frequency of LM ranged from 15.8% in 1989 to 19.7% in 2001 and of LM
      with concomitant Mumps ranged from 10.5% in 1989 to 4.7% in 1995, when the last
      cases were registered. CONCLUSION: It is probable that the mumps vaccine campaign
      has influenced the absence of LM with concomitant Mumps, from 1996 to 2001.

PMID- 14595474
TI  - Immunologic aspects of West syndrome and evidence of plasma inhibitory effects on
      T cell function.
AB  - STUDY OBJECTIVE: The purpose of this study was to assess the extent of immune
      dysfunction in a well-defined group of epileptic patients: children with
      diagnosis of West syndrome (WS) or with transitions to another age-related EEG
      patterns, the multifocal independent spikes (MIS), and the slow spike-wave
      complexes (Lennox-Gastaut syndrome - LGS). Thus, WS was studied at different
      points of the natural evolutive history of the disease. METHOD: A group of 50
      patients (33 with WS, 10 with LGS and 7 with MIS) and 20 age-matched healthy
      controls were submitted to enumeration of T lymphocyte subsets: CD1, CD3, CD4,
      CD8, CD4/CD8 ratio and lymphocyte proliferation assay to phytohaemagglutinin
      (PHA), in the presence of autologous and AB, homologous plasma.
      Dinitrochlorobenzene (DNCB) skin test sensitization was performed only in
      patients. Determinations of IgG, IgA, and IgM serum levels were compared to
      standard values for Brazilian population in different age ranges. RESULTS:
      Sensitization to DNCB showed absent or low skin reactions in 76% of the patients.
      High levels of IgG (45.7%) and IgM (61.4%), and lower levels of IgA (23.9%) were
      detected in the serum of the patients. Enumeration of lymphocyte subsets in
      peripheral blood showed: low CD3+ (p<0.05), low CD4+ (p<0.05), high CD8+ (p<0.01)
      and low CD4+ / CD8+ ratio (p<0.001). The proportion of CD1+ cells in the control
      group was less than 3%, while ranged between 6 and 11 % in 18% of the patients.
      The in vitro PHA-induced T cell proliferation showed significantly low
      blastogenic indices only when patients, cells were cultured in presence of their
      own plasma. No differences in blastogenic indices were observed when the cells of
      patients and controls were cultured with human AB plasma. CONCLUSION: The
      immunodeficiency in WS was mainly characterized by anergy, impaired cell-mediated
      immunity, altered levels of immunoglobulins, presence of immature thymocytes in
      peripheral blood and functional impairment of T lymphocytes induced by plasma
      inhibitory factors.

PMID- 14595475
TI  - A dual action of alpha-lipoic acid in the brain: an electrophysiological
      evaluation.
AB  - Oxidative stress causes metabolic and structural abnormalities during
      reperfusion. In an animal model of electrophysiological evaluation of cerebral
      ischemia-reperfusion, alpha-lipoic acid effect on the oxidative stress was
      studied by mean absolute amplitude of EEG spectra evaluation. The left carotideal
      infusion of 3.03 mM alpha-lipoic acid in Wistar rats after cerebral ischemia and
      reperfusion caused initial reduction and partial final recuperation of the
      various EEG spectral frequency mean absolute amplitudes (p<0.05). The left
      intracarotideal infusion of 6.06 mM alpha-lipoic acid significantly reverted the
      induced depression of mean absolute amplitude of theta and delta spectra.
      Nevertheless there was an increasing pattern of ischemia demonstrated by mean
      absolute amplitude depression of almost all EEG spectra with 60.6 mM alpha-lipoic
      acid infusion. These observations suggest that, depending on the administered
      concentration, alpha-lipoic acid may act in a dual way, protecting from ischemia
      at lower concentrations and worsening this process at higher doses.

PMID- 14595476
TI  - Acute subdural hematoma and diffuse axonal injury in fatal road traffic accident
      victims: a clinico-pathological study of 15 patients.
AB  - OBJECTIVE: Although acute subdural hematoma (ASDH) and diffuse axonal injury
      (DAI) are commonly associated in victims of head injury due to road traffic
      accidents, there are only two clinico-pathological studies of this association.
      We report a clinical and pathological study of 15 patients with ASDH associated
      with DAI. METHOD: The patients were victims of road traffic accidents and were
      randomly chosen. The state of consciousness on hospital admission was evaluated
      by the Glasgow coma scale. For the identification of axons the histological
      sections of the brain were stained with anti-neurofilament proteins. RESULTS:
      Twelve of the 15 patients were admitted to hospital in a state of coma; in three
      patients, the level of consciousness was not evaluated, as they died before
      hospital admission. CONCLUSION: The poorer prognosis in patients with ASDH who
      lapse into coma immediately after sustaining a head injury, as described by
      several authors, can be explained by the almost constant association between ASDH
      and DAI in victims of fatal road traffic accidents.

PMID- 14595477
TI  - Functional evaluation of temporary focal cerebral ischemia: experimental model.
AB  - OBJECTIVE: Despite cerebral ischemia being a frequent clinical pathologic state,
      the tolerance of neural tissue to oxygen absence and to reperfusion is
      controversial. This study aims to evaluate the effects of focal cerebral
      ischemia/reperfusion, by analyzing the mitochondrial respiration. METHOD: Sixty
      four adult rats underwent focal cerebral ischemia by middle cerebral artery
      occlusion, during 15, 30 and 60 minutes, followed by 10 minutes or 19 hours of
      reperfusion. The effects of ischemia were analyzed measuring the O2 consumption
      by mitochondria in the ischemic and non-ischemic areas. RESULTS: There was
      compromise of the mitochondrial respiration after 30 and 60 minutes of ischemia,
      followed by 10 minutes of reperfusion but there was no alteration in this
      function after 19 hours of reperfusion. CONCLUSION: Compromise of the
      mitochondrial function occurred after 30 minutes of ischemia but, until one hour
      of ischemia, if the reperfusion was prolonged there was no evidence of
      ischemic/reperfusion injuries.

PMID- 14595479
TI  - [Platelet aggregation test: application in the control of antiplatelet
      aggregation in the secondary prevention of stroke].
AB  - INTRODUCTION: Stroke is the leading cause of death in Brazil. The risk of
      suffering a recurrent stroke is around 30% in 5 years. Antiplatelet therapy has
      been frequently used to prevent recurrent strokes without laboratory control.
      OBJECTIVE: To determine the value of the platelet aggregation test in the control
      of antiplatelet aggregation in the secondary stroke prevention. METHOD:
      Retrospective study from January 1990 to January 2001 with 189 patients with
      stroke that were followed up during this period with platelet aggregation curve.
      Patients with cardioembolic disease were excluded. Low aggregation rates of
      platelet aggregation activated by ADP and/or epinephrine lower or equal to 50%
      were considered. Patients were followed up for a period from one to six years to
      verify differences in stroke recurrence. RESULTS: Nine patients had had a
      recurrent stroke; 2,6% of the strokes occurred among the group with low
      aggregaton and 15,1% among the group with normal aggregation (0,03<OR<0,69,
      p<0,05). Most of the cases occurred in the second year after the first stroke.
      CONCLUSION: Platelet aggregation curve is a valid and a helpful laboratory test
      to therapeutic control of antiplatelet aggregation in secondary stroke
      prevention.

PMID- 14595478
TI  - Antibodies to the atherosclerotic plaque components beta2-glycoprotein I and heat
      shock proteins as risk factors for acute cerebral ischemia.
AB  - One third of cases of cerebral ischemia have no clear etiology. A humoral
      response to the atherosclerotic plaques components beta2-glycoprotein l (beta2
      gpl) and heat-shock proteins (Hsp) might be involved in the pathogenesis of
      stroke. This case-control study includes a complete profile of anti-beta2-gpl
      antibodies and testing of IgG antibodies to the 60/65 kilodaltons (kDa) Hsp in
      stroke patients. Ninety-three patients with acute ischemic stroke and 93 controls
      were evaluated for age, sex, race, hypertension, smoking, previous cardiopathy,
      diabetes mellitus, hypercholesterolemia and previous history of cerebral
      ischemia. lgG/lgM/lgA anticardiolipin (aCL) and anti-beta2-gpl antibodies, as
      well as lgG antibodies to human 60 kDa Hsp and to Mycobacterium bovis 65 kDa Hsp,
      were detected by immunoassay. Adjusted odds ratios (OR) were calculated by
      logistic regression. The adjusted OR for IgA anti-beta2-gpl antibodies was 4.6
      (90%Cl 1.5 to 14.3; p = 0.025). The non-adjusted OR for IgG antibodies to Hsp 60
      was 26.1. The adjusted OR for IgG antibodies to Hsp 65 was 3.2 (90%Cl 1.2 to 8.3;
      p = 0.044). The adjusted OR for lgG to any Hsp (60 or 65) was 4.8 (90%Cl 1.9 to
      12.1; p = 0.006). This study demonstrates that elevated IgA anti-beta2-gpl and
      lgG anti-Hsp 60/65 antibodies are associated with increased risk of ischemic
      stroke. The association occurred independently of other risk factors. This
      humoral response might link autoimmunity, thrombophilia and atherosclerosis in
      stroke patients.

PMID- 14595480
TI  - [Kinesiotherapy prevents shoulder pain in hemiplegic/paretic patients on sub
      acute stage post-stroke].
AB  - BACKGROUND: Painful shoulder is considered the most common complication of
      hemiplegic/parethic (H/P) stroke patients. It is a negative factor for neuromotor
      recovery. PURPOSE: To study the effects of kinesiotherapy treatment on shoulder
      pain prevention, and as a secondary endpoints, to analyze muscle strength of H/P
      shoulder looking at basic functional active mobility. METHOD: Twenty one
      inpatients (12 men, 9 women) aged 26 to 87 years, with post-stroke H/P were
      submitted to thirty minutes daily program kinesiotherapy, started at 48 hours
      post-stroke up to their hospital discharge. Patients were evaluated pre and post
      treatment according to the presence or absence of shoulder pain, movements and
      shoulder strength, and for presence or absence of basic functional movements.
      RESULTS: No patient complaining of shoulder pain at the hospital discharge
      (p<0.001). The muscle strength improved signifcantly for elevation, protusion,
      abduction and flexion of the shoulder (p<0.001). There was improvement also for
      functional mobility on moving from dorsal to lateral recumb, from lateral recumb
      to a seated position and in keeping the seated position (p<0.001). CONCLUSION:
      Kinesiotherapy in acute phase of stroke prevented shoulder pain.

PMID- 14595481
TI  - [Lay knowledge about stroke].
AB  - The significance of the risk factors and the rapid diagnosis of encephalic
      vascular disease (EVD) is the reason for this research, where the authors decided
      to register and analyze the non-medical people knowledge about these risk factors
      and the symptoms of this group of disease. For this purpose a questionnaire with
      questions about these facts was applied to 500 voluntaries without pre-selection,
      72.6% of them with ages between 16-35 years old, and the answers analyzed by
      statistical methods. The authors recognized that the risk factors has a good
      level of knowledge by this population (87.8 % for hypertension, 76.8 % for
      smoking, 70.8 % for obesity, 68.7 % for sedentary persons, 66.7 % to stress, 66.3
      % to alcohol ingest, 60.7 % for fat diet, 59 % to illicit drugs) while the signs
      and symptoms of EVD has a minor level of knowing and correction: lost sensitivity
      70.3 %, headache 64.2 %, twisted mouth 59.5 %, lost or altered speech 57.5 %,
      dizziness 56 %, syncope 51.7 %, amaurosis 50.3 %, disequilibrium 45 %, deafness
      31.2 %, weakness 41.1 %, nervousness 20.7%, chest pain 20.2 %, fatigue 15.3 % and
      tinnitus 18.9 %. According this data, the authors suggest that the correction or
      prevention of risk factors as well the precocious medical attention by the
      recognition of symptoms of EVD must be the object of public health programs.

PMID- 14595482
TI  - [Suggestions for utilization of the mini-mental state examination in Brazil].
AB  - Mini-metal state examination (MMSE) is a screening test to detect cognitive
      impairment. The objectives of the present study are to describe some adaptations
      for use of MMSE in Brazil and to propose rules for its uniform application.
      METHOD: We evaluated 433 healthy subjects using the MMSE and verified the
      possible influence of demographic variables on total scores. RESULTS: Educational
      level was the main factor that influenced performance, demonstrated by ANOVA:
      F(4,425) = 100.45, p<0.0001. The median values for educational groups were: 20
      for illiterates; 25 for 1 to 4 yrs; 26.5 for 5 to 8 yrs; 28 for 9 to 11 yrs and
      29 for higher levels. CONCLUSION: The MMSE is an excellent screening instrument
      and definitive rules are necessary for comparison purposes.

PMID- 14595483
TI  - [Mini-mental state examination in community-dwelling elderly: preliminary data
      from Santo Antonio de Padua, Rio de Janeiro, Brazil].
AB  - OBJECTIVE: To define mini-mental state examination (MMSE) global scores, by age
      and education in elderly in Santo Antonio de Padua, Rio de Janeiro, Brazil.
      METHOD: Elderly > 65 years-old (n=341; m=109, f=232) responded to MMSE. Sample
      was divided by age and education: young old (65-84 years)/oldest old (>85 years),
      illiterates, low/medium schooling. MMSE scores were compared using t test of
      Student, Mann-Whitney and Tukey (p<0.05). RESULTS: Young and oldest old's mean
      age were 73.13 5.27; 88.00 4.90, respectively. Young old MMSE score was 19.91
      5.35 and oldest old was 16.90 4.96. There was a significant difference between
      the groups (p=0.01). Illiterate and educated elderly scored 17.08 4.42 and 22.34
      4.94, respectively (p<0.0001). Illiterate and educated young old (age=73.61 +/-
      5.26; 72.67 +/- 5.26) scored 17.29 +/- 4.40 and 22.42 +/- 4.98, respectively.
      MMSE shows significant difference between groups of young old (p<0.0001). MMSE of
      illiterate and educated oldest old (age=86.50 +/- 1.09; 90.25 +/- 7.34) were
      14.33 +/- 3.89 and 20.75 +/- 3.85, respectively. CONCLUSION: Schooling and age
      influence on MMSE. These results do not compare with those of developed countries
      taking education as a variable.

PMID- 14595484
TI  - [Epilepsy surgery in childhood: neuropsychological and quality of life
      assessments].
AB  - PURPOSE: To perform neuropsychological and quality of life assessments before and
      after epilepsy surgery in children; to correlate these parameters with clinical
      findings. METHOD: Nine children with refractory epilepsy were evaluated before
      and six months after the surgical treatment with a comprehensive
      neuropsychological battery and quality of life questionnaire. Children had
      variable etiologies and surgical procedures. RESULTS: IQ changes did not occur;
      two children with temporal lobe epilepsy due to tumor had important behavior
      impairment after surgery despite complete seizure control; best
      neuropsychological improvement was seen in the child who had Rasmussen's
      encephalitis and underwent hemispherectomy. Social aspects, drug side effects,
      seizure perception and the overall level of quality of life improved after
      surgery. CONCLUSION: Quality of life improvement was clearly correlated with
      seizure control; nevertheless, neuropsychological improvement depended on several
      factors, such as etiology, type of epilepsy and surgery.

PMID- 14595485
TI  - [Somatosensory evoked spikes and epileptiform activity in "normal" children].
AB  - Little is known about somatosensory evoked spikes (SES) in the EEG of normal
      children. We studied the occurrence of SES and spontaneous epileptiform activity
      (SEA) in 173 normal children ageg 7 to 11 years. During the EEG ten taps were
      applied to both hands and feet. The occurrence of high voltage potentials evoked
      by each stimulation of one or both heels or hands (SES) and the occurrence of SEA
      were evaluated. SEA was observed in four children (2.3 %): central/parietal
      spikes in two cases, generalized spike-and-wave in one, and parietal/midtemporal
      spikes in one case. A ten years old girl (0,58%) had SES on median parietal
      region by tapping the left foot. This EEG was otherwise normal. Our findings of
      SEA are similar to those obtained in other normal populations. SES can be
      observed in normal children. These SES suggest that we are dealing with an age
      related functional phenomenon.

PMID- 14595486
TI  - [Quantitative electroencephalography in healthy school-age children: analysis of
      band power].
AB  - Quantitative EEG aspects are studied with respect to age, sex and sociocultural
      parameters. A total of 162 children, from 7 to 11 years, neurologically and
      intellectually normal was studied. They were submitted to anamnesis, neurological
      examination, Raven test, school performance test, digital electroencephalogram
      and quantitative electroencephalogram analysis. There was a decrease in absolute
      and relative delta and theta power and an increase in alpha 2 relative power with
      the increase of age. These findings are similar to those observed in studies from
      Europe, Asia and North America. Absolute delta and alpha power were higher in
      children with better scores in school performance test. There were no significant
      differences in quantitative electroencephalographic parameters according to sex
      and the mother's educational level.

PMID- 14595487
TI  - [Follow-up of low birth weight infants: language acquisition].
AB  - The objective of this work was to follow-up language development of full-term
      infants/small for gestational age (RNT/PIG) and preterm infants/adequate for
      gestational age (RNPT/AIG). The assessments were done monthly, up to their 18th
      months of age. Twenty infants were evaluated, 10 of each group. The Ethical
      Committee of the institution approved the project. It was used the Protocol for
      Anamneses and the Early Language Milestone Scale - ELM Scale. Both groups were
      compared with 47 full term, adequate for gestational age infants. The results had
      shown that up to the 6th month, the infants showed a normal performance for their
      age. In the 9th month, there was a delay in babbling production. In the 12th
      month, infants of the RNT/PIG group showed a significant statistically delay
      expressing polysyllabic babbling and infants of the RNPT/AIG group showed delay
      in the production of the first words. In the 18th month, the delay persisted in
      one infant of the RNT/PIG group.

PMID- 14595488
TI  - [Neonatal Doppler velocimetry in full term small-for-gestational age newborns].
AB  - This study aimed to evaluate the cerebral blood flow of full term small-for
      gestational age newborns, using cranial ultrasound Doppler at birth. This study
      was performed at CAISM/UNICAMP (Tertiary Health Center for Women). Sixty term
      newborns were selected and divided in two groups: appropriate-for-gestational age
      (AGA) (36 neonates) and small-for-gestational age (SGA) (24 neonates). Cranial
      ultrasound Doppler evaluation was performed on both groups, between 24 and 48
      hours after birth. Cerebral blood flow velocity (CBFV) was lower in the small-for
      gestational age group, in the anterior cerebral artery (ACA). Doppler
      measurements were different statistically between the groups only for values
      related to peak systolic flow velocity (PSFV) and mean flow velocity (MFV) in the
      ACA. There was no significant difference for any evaluated parameters of flow
      velocity in the middle cerebral artery (MCA). It was concluded that SGA newborns
      showed PSFV and MFV significantly reduced only in the ACA. Weight/gestational
      age, neonatal polycythemia and mean arterial blood pressure values were
      statistically related to MFV in the ACA. In presence of fetal suffering, mean
      arterial blood pressure values and smoking in the pregnancy were statistically
      related to MFV in the MCA.

PMID- 14595489
TI  - [Myelopathy: clinical considerations and etiological aspects].
AB  - We studied 97 inpatients with myelopathy at the University Hospital Lauro
      Wanderley from 1985 to 2002. Ages ranged from 10 to 78 years and average age was
      39.8 years. All patients were examined by neurologist. Cerebrospinal fluid (CSF)
      was analysed in 44 (45.3%) cases and immunofluorescence reactions and/or ELISA in
      CSF were made in 32 (32.9%) cases. Radiologic investigation of the vertebral
      spine and spinal cord of the 32 (32.9%) cases consisted of 8 radiographies, 10
      computed tomography and 14 magnetic resonance image. In 41 (42.2%) cases the
      lesions were situated in the lower dorsal and lumbar level and complete
      transverse lesion were registred in 61 (62.8%) cases. There was predominance of
      transverse myelitis (43.2%) and spinal cord compression (15.46%). Spinal cord
      schistosomiasis was the form more often of the transverse myelitis (13.4%).

PMID- 14595490
TI  - [Clinical and epidemiological aspects of neurocysticercosis in Brazil: a critical
      approach].
AB  - With the objective to show the characteristics of neurocysticercosis (NCC) in
      Brazil, was performed a critical analysis of national literature which showed a
      frequency of 1.5% in autopsies and 3.0% in clinical studies, corresponding to
      0.3% of all admissions in general hospitals. In seroepidemiological studies the
      positivity of specific reactions was 2.3%. Brazilian patient with NCC presents a
      general clinical-epidemilogical profile (31-50 years old man, rural origin,
      complex partial epileptic crisis, increased protein levels or normal CSF, CT
      showing calcifications, constituting the inactive form of NCC), and a profile of
      severity (21-40 years old woman, urban origin, vascular headache and intracranial
      hypertension, typical CSF syndrome of NCC or alteration of two or more CSF
      parameters, CT showing vesicles and/or calcifications, constituting the active
      form of NCC). Although two localities from the state of S o Paulo have 72:100000
      and 96:100000/habitants as prevalence coefficients, regional and national
      prevalences are very underestimated. Some aspects related to underestimation of
      NCC prevalence in Brazil are discussed.

PMID- 14595491
TI  - [Septic spondylodiscitis: diagnosis and treatment].
AB  - We studied retrospectively 24 patients with septic discitis of different
      etiologies (hematogenic, primary and infantile) and the different aspects
      involved in its diagnosis and treatment. Erythrocyte sedimentation rate proved to
      be a valuable parameter and should always be interpreted carefully along with the
      clinical and neuroimaging findings. Biopsies should be reserved for doubtful
      cases with atypical course. Clinical treatment should be initiated after the
      following situations have been ruled out: sepsis, neurological deficit, severe
      deformity, epidural abscess and foreign body (primary disease). The surgical
      approach may be chosen based on the stage of disease, being preferably posterior
      in suppurative forms and anterior in the non-suppurative stage. Based on our
      experience and on information gathered by literature review, we propose an
      algorithm to guide diagnosis and treatment in patients with septic discitis.

PMID- 14595492
TI  - [Transnasal endoscopic surgery of the sellar region: study of the first 100
      cases].
AB  - An endoscopic endonasal transsphenoidal approach to the sella was performed in
      100 consecutive patients, with a follow up from 3 to 55 months: 57 females and 43
      males, age ranging from 14 and 70 years. 76 cases pituitary adenomas: 22 were
      acromegaly (7 microadenomas and 15 macroadenomas); 21 null cell adenomas (3
      microadenomas and 18 macroadenomas); 19 Cushing disease (11 microadenomas and 8
      macroadenomas), 10 prolactinomas (6 microadenomas and 4 macroadenomas), and 4 LH
      adenomas (4 macroadenomas). In this serie, remission was achieved in 44.8% for
      macroadenomas, 60% for acromegaly, 27.7% for null cell adenoma, 50% for Cushing
      disease, 50% for prolactinomas and 50% for LH adenomas, and 81.4% for
      microadenomas 85% for acromegaly, 100% for null cell adenoma, 81.8% for Cushing
      disease, 66% for prolactinoma. We had also four craniopharyngiomas, four
      sphenoidal mucocele, three sphenoidal aspergillus, one Rathke cyst, one
      hypophysitis, one cavernous aneurysm, one encefalocele, one intrasellar
      meningioma, one intrasellar tuberculoma and a sphenoid fibrous dysplasia. In this
      series we also had six fistulas of the anterior base that were completely cured.
      We had a mortality of 2, one null cell giant adenoma in a 57 years old man and
      another patient, 38 years old, with a giant craniopharyngioma. The morbidity was:
      two cured meningitis, three cured fistulas, and two permanent diabetes insipidus.
      Endoscopic endonasal transsphenoidal surgery in this series resulted with
      comparable surgical outcomes to conventional microscopic transsphenoidal surgery.
      The advantages of this technique have been represented by an easier access to the
      lesion, better visualisation and increased illumination of the surgical sites,
      microdissection of the tumor with maximum preservation of the pituitary function,
      and reduction of hospitalization times and coasts. The main limits have been the
      reduction of field depth, constant need of manual control of the endoscope, and
      required experience of the endoscope technique.

PMID- 14595493
TI  - Leptomeningeal dissemination of pilocytic astrocytoma at diagnosis in childhood:
      two cases report.
AB  - Pilocytic astrocytoma (PA) is a benign tumor that rarely spread along the
      neuraxis. At the moment there are no more than five cases of leptomeningeal
      dissemination (LD) from PA at diagnosis described in the literature. Different
      patterns of presentation or recurrence may be noted: local recurrence, malignant
      transformation, multicentric disease or metastatic disease. LD and multicentric
      disease can be distinct pathological entities. We report two cases and analyse
      literature, emphasizing leptomeningeal spread at presentation. Hydrocephalus,
      biopsy and parcial ressection are likely to be favorable factors to the
      occurrence of LD. Otherwise, LD may be part of natural history of PA, as
      evidenced by its ocurrence in non-treated cases.

PMID- 14595494
TI  - Oscillucusis and sudden deafness in a migraine patient.
AB  - Migraine is a complex disease that includes neurologic, gastrointestinal and
      autonomic symptoms, although headache is most common feature. In a portion of
      cases headache is preceded by focal neurologic symptoms termed auras. Auditory
      symptoms only rarely occur as part of an aura. We describe a patient whose 13
      year migraine history that included the abnormal perception an oscillation of the
      intensity of ambient sounds (oscillucusis). During a migraine attack immediately
      after oscillucusis, the patient developed acute and permanent sudden deafness.
      Clinical and neurologic examinations revealed only profound hearing loss in her
      left ear. Audiometric testing confirmed the sensorineural nature of the hearing
      loss. The clinical aspects and physiopathology of auditory symptoms in this case
      and in patients with migraine is reviewed.

PMID- 14595495
TI  - Hoffman's syndrome: pseudohypertrophic myopathy as initial manifestation of
      hypothyroidism. Case report.
AB  - The frequency of myopathy in hypothyroidism ranges from 30 to 80%. The major
      symptoms related are weakness, muscular cramps and myalgia. The
      pseudohyperthrophic form is called Hoffman's syndrome. The electrophysiological
      study reveals myopathy, neuropathy or mixed pattern. Laboratorial investigation
      generally shows increased levels of muscle enzymes and low serum thyroid
      hormones, with thyrotrophic-stimulating hormone (TSH) elevated. The treatment
      consists in hormone replacement and the prognosis is good in most of the cases.
      We report an adult male who developed muscular cramps, myalgia, weakness,
      pseudohyperthrophy, associated with facial edema and alteration of his voice. The
      muscle enzymes were increased and T4 was undetectable with a raised level of TSH.
      The myopathy was the initial manifestation of hypothyroidism in this case.

PMID- 14595496
TI  - Disseminated tuberculosis in a pregnant woman presenting with numerous brain
      tuberculomas: case report.
AB  - Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis, which
      has the pulmonary form as the most common presentation. Dissemination of the
      disease is common in immunocompromised patients, but immunodeficiency related to
      pregnancy severe enough to cause dissemination of the Mycobacteria is exceedingly
      rare. When dissemination occurs, any organ may be affected and in central nervous
      system, the infection presents as meningitis and single brain parenchyma
      tuberculomas. We report the case of a 17 year-old woman at the 34th week of
      pregnancy with respiratory and high intracranial pressure symptoms. On the day
      before admission she had a sudden onset of paraparesis and urinary retention and
      ten hours after the delivery she presented with paraplegia. The chest X-ray and
      CT scan were compatible with miliary tuberculosis. The cranial CT scan revealed
      numerous rounded hypodense lesions located at cerebral and cerebellar
      hemispheres, which presented ring-like enhancement after contrast injection. The
      patient underwent a craniotomy with biopsy of the lesions confirming the
      diagnosis of brain tuberculomas. The three-drug regimen was started and the
      cranial CT scan performed a year after diagnosis showed no brain lesions. We
      emphasize the aggressive dissemination of the disease in this case associated
      with pregnancy and the importance of early diagnosis and institution of therapy
      resulting in regression of the lesions.

PMID- 14595498
TI  - [Spinal cord intramedullary cavernous haemangioma: case report].
AB  - The intramedullary cavernous haemangioma is a low flow vascular anomaly curable
      through surgical resection, howewer if the precocious diagnosis and the
      appropriate therapeutics are not done it can cause serious neurological sequels.
      It is extremely rare the occurrence of intramedullary cavernous haemangioma. We
      report the case of a 33 year-old woman patient with an intramedullary cavernous
      angioma at T6-T7, that presented a clinical picture of slow and progressive
      spinal cord compression, with an important recent worsening. The magnetic
      resonance of the thoracic column demonstrated a T6 - T7 a intramedullary
      expansive lesion wich presented hypointense on T1 and discretely hyperintense on
      T2 with a small hypointense area in the two sequences. The patient was submitted
      to late surgical treatment and did not presented neurological recovery. The
      clinical and imagelogy pictures, and the importance of instituing precociously
      the appropriate treatment of this entity is reviewed, analyzed and discussed.

PMID- 14595497
TI  - [Central nervous system involvement by histoplasmosis as the unique manifestation
      of this disease in immunocompetent patients: presentation of two cases].
AB  - We present two patients with central nervous system involvement as the unique
      clinical manifestation of histoplasmosis. A clinical review confirmed the
      infrequency of this form of the disease, overall in childhood, being one of these
      cases the youngest in Brazilian reports. Comments about the diversity of clinical
      presentation and main differential diagnosis are presented. We analyze the
      serologic and cerebrospinal fluid results and, finally, discuss the drugs and
      duration of treatment.

PMID- 14595499
TI  - [Intramedullary epidermoid tumor: case report].
AB  - A rare case of an epidermoid intramedullary spinal cord tumor, extending from the
      second to the fourth thoracic vertebra is reported, in a 15 years old girl,
      surgically treated successfully. The clinical feature, the ethiopatogeny and a
      literature review will be discussed.

PMID- 14595500
TI  - [Hyponatremic coma induced by oxcarbazepine: case report].
AB  - We report a rare case of severe hyponatremia with coma induced by the use of
      oxcarbazepine after one month of treatment, in pos-operatory of neurosurgery. We
      discuss the importance of this condition and its differential diagnosis.

PMID- 14595501
TI  - [Delusional parasitic infestation and folie a deux: case report].
AB  - Shared psychiatric disorder (folie   deux) is a rare condition. But its
      prevalence can be 5-25% in patients with delusional parasitic infestation. We
      report the a case of a 62 years-old female with psychotic symptoms. For 15 years,
      she has lived with her younger sister. Since the patient was well-controled, her
      sister interrupted her antipsychotic drug administration. So, the patient
      initiated delusional parasitic infestation accompanied by visual hallucinations.
      Her sister, who did not have psychiatric history, initiated to believe that the
      patient was really infested. Moreover, she started to believe that was infested
      by the patient. This case report aims to discuss the relation between folie  
      deux and delusional parasitic infestation.

PMID- 14595502
TI  - [Neuropsychiatric disturbances in Wilson's disease and use of electroconvulsive
      therapy: case report].
AB  - Wilson's disease consists in a inborn error of metabolism with marked
      neuropsychiatric manifestations. These manifestations need to be correctly
      identified and treated. There are four neuropsychiatric symptoms clusters
      established for Wilson's disease patients: behavior and/or personality disorders,
      mood disorders, cognitive deficits, and psychotic manifestations. Although such
      patients are more commonly seen in neurological and hepatological settings,
      mental health professionals must keep in mind a high level of suspicion, once
      first presentations may be of psychiatric nature. This study presents a review of
      literature about neuropsychiatric aspects of Wilson's disease, emphasizing
      diagnostic issues. It is presented the case of a 26 years old male patient
      initially with psychiatric polimorfic symptoms. The treatment of this patient
      with electroconvulsive therapy is presented, adding a report of this therapeutic
      modality, applied to that case, to the two only previous records in the
      literature.

PMID- 14595503
TI  - [A Brazilian Portuguese version for the ADCS-CGIC scale].
AB  - Given increasing research into new therapies for dementia, especially for
      Alzheimer disease, it has become clear that traditional methods of evaluation,
      centered on cognition, have proved insufficient. Thus, scales for behavioral
      disturbances and activities of daily living have been added. Nevertheless, some
      observations of clinical significant changes, as reported by caregivers, could be
      overlooked. Clinician's impression of global change scales (CIGIC) are based on
      broader information and may detect more subtle changes. Typically they take into
      consideration caregiver information, that which is seen by the health
      professional during the interview, and may also include brief cognitive tests. We
      present a Brazilian Portuguese version of a widely used scale of this type,
      specifically designed for Alzheimer disease (ADCS-CGIC), being the result of the
      recommended method of translation, back-translation and version by panel
      consensus.

PMID- 14595505
TI  - Neonatal anthropometry and neonatal outcome.

PMID- 14595506
TI  - Weight-for-length relationship at birth to predict neonatal diseases.
AB  - CONTEXT: Intrauterine growth curves are extremely useful for classifying newborn
      children and predicting neonatal diseases. However, such curves rely on knowledge
      of the gestational age, which is not always easily obtained. Therefore, the study
      of other anthropometric measurements and their interrelationship is always
      desirable, in order to attain such objectives. OBJECTIVE: To evaluate whether
      newborns' birth weight and length can identify neonatal diseases, independent of
      knowledge of the gestational age. TYPE OF STUDY: Retrospective study. SETTING:
      Institute of Teaching and Research of Hospital Israelita Albert Einstein, Sao
      Paulo, Brazil. PARTICIPANTS: During the period from February 1995 to January
      1998, 8,397 live newborns were studied in the hospital's maternity ward.
      PROCEDURES: The weight and length of live newborns were obtained at birth, thus
      allowing the analysis of weight-for-length adequacy, i.e. the distribution of
      birth weight for each class of birth length. These measurements were determined
      for the first 4,634 live newborns and the 10th and 90th percentiles were
      established. These parameters were applied to the next 3,763 consecutive newborns
      of the same population. The relationships between these variables and some
      neonatal diseases were investigated. The significance level adopted was p<0.05.
      MAIN MEASUREMENTS: Birth weight and length, weight-for-length adequacy (10th and
      90th percentiles for weight distribution in each 1-cm length class),
      weight/length index (10th and 90th percentiles of newborn's weight divided by the
      length) and frequent neonatal diseases in this population. RESULTS: There was a
      significant association of adequacy and index with the following affections:
      asphyxia, jaundice, hypoglycemia, hypomagnesemia, congenital pneumonia, pulmonary
      hypertension and sepsis. Additionally, there was a relationship between the index
      and respiratory distress syndrome, transient tachypnea and persistent ductus
      arteriosus. CONCLUSIONS: Weight-for-length adequacy and weight/length index
      alone, without the knowledge of gestational age, were able to identify newborns
      at risk for some selected neonatal diseases.

PMID- 14595507
TI  - Evolution of patients with squamous cell carcinoma of upper aerodigestive tract.
AB  - CONTEXT: Local and regional recurrences are frequent in patients with squamous
      cell carcinoma of the upper aerodigestive tract and early diagnosis is important
      for salvage treatment. OBJECTIVE: To identify the period of highest risk for the
      development of recurrences after surgical treatment of squamous cell carcinoma of
      the upper aerodigestive tract, in spite of radical therapy, in order to plan the
      follow-up for these patients. TYPE OF STUDY: Cross-sectional, descriptive.
      SETTING: Department of Head and Neck Surgery/Otorhinolaryngology, Heliopolis
      Hospital (Hosphel), Sao Paulo, Brazil. PARTICIPANTS: A review was made of the
      hospital records of 889 patients with squamous cell carcinoma of the upper
      aerodigestive tract surgically treated between October 1977 and December 1996:
      364 had oral cavity tumors, 107 had tumors of the oropharynx, 152 of the
      hypopharynx and 266, larynx tumors. The disease was stage I in 14 patients, stage
      II in 117, stage III in 352, stage IV in 397 and 9 patients were not staged. MAIN
      MEASUREMENTS: The interval between treatment and recurrence of disease was
      evaluated. The results were expressed as medians, quartiles (25% to 75%) and
      percentiles (10% to 90%). The annual incidence of recurrences and second tumors
      was calculated. RESULTS: Seventy-four percent of the recurrences were diagnosed
      within 18 months post-treatment. The local and regional recurrences and distant
      metastases showed medians of 270, 210 and 435 postoperative days respectively.
      The incidence of a second primary tumor varied from 2 to 3.1% a year. CONCLUSION:
      The majority of recurrences occurred within 18 months after the initial surgical
      treatment. The incidence of a second tumor remained stable after the first post
      treatment year.

PMID- 14595508
TI  - Prevalence of thyroid dysfunction in patients with acute atrial fibrillation
      attended at a cardiology emergency room.
AB  - CONTEXT: Atrial fibrillation occurs frequently in patients with thyrotoxicosis,
      while it has low prevalence in adults of the general population. The prevalence
      of thyroid dysfunction in subjects with atrial fibrillation is 0 to 24%, a wide
      variation that is attributed to the different methodologies applied. However,
      continuous use of amiodarone in patients with previous atrial fibrillation may
      interfere with these prevalence rates. OBJECTIVE: In this study, we present the
      prevalence of thyroid dysfunction in adult patients who presented at a cardiac
      emergency room with acute atrial fibrillation, using a sensitive thyroid
      stimulating hormone (TSH) assay and triiodothyronine (T3) and thyroxine (T4)
      determination. TYPE OF STUDY: Cross-sectional study. SETTING: Emergency room of a
      tertiary care facility. PARTICIPANTS: A total of 72 patients with atrial
      fibrillation who presented at the emergency room not more than 48 hours after its
      onset. PROCEDURES: A standardized questionnaire and 12-lead electrocardiogram
      were applied, and T3, T4 and TSH were determined. MAIN MEASUREMENTS: TSH, T3 and
      T4 determination. RESULTS: Among these patients, 16.6% had altered thyroid
      function tests: 6.9% had hyperthyroidism, 5.6% hypothyroidism and 4.2% had
      increased T4 levels, by means of amiodarone use. CONCLUSION: The high prevalence
      of thyroid dysfunction in our study, especially hyperthyroidism, suggests that
      routine thyroid testing with sensitive thyroid-stimulating hormone assay is
      required in patients with acute atrial fibrillation.

PMID- 14595509
TI  - p53, estrogen and progesterone receptors in diagnostic curettage for endometrial
      adenocarcinoma and their correlation with morphological data and disease stage at
      hysterectomy.
AB  - CONTEXT: Diagnostic staging is an important prognostic factor for endometrial
      adenocarcinoma. Apart from the histological type and histological grade, some
      markers seem to be associated with the stage and biological behavior of the
      disease. Among these are p53, estrogen and progesterone receptors. OBJECTIVE: The
      objectives of the present study were: to compare histological type and grading of
      endometrial carcinoma in curettage and hysterectomy samples; to assess expression
      of p53, estrogen and progesterone receptors in curettage specimens; and to
      correlate these data with morphology and staging of the disease in hysterectomy
      specimens. TYPE OF STUDY: Retrospective. SETTING: Department of Pathology,
      Faculdade de Ciencias Medicas, Universidade Estadual de Campinas. SAMPLE:
      Histological diagnosis from 51 consecutive files. PROCEDURES: Immunohistochemical
      reactions for p53, estrogen and progesterone receptors via the avidin-biotin
      peroxidase method in 51 curettage samples endometrial carcinoma were compared
      with the morphological data and disease stage in hysterectomy. Marker expression
      was correlated with histological type and grade and the final stage of the
      disease. RESULTS: According to the histological type: 44 cases (86%) were of
      endometrioid and 7 (14%) non-endometrioid carcinoma. p53 expression was observed
      in 16% of endometrioid and 71% of non-endometrioid cases (p<0.05). Although
      estrogen expression was more evident in endometrioid (54%) than non-endometrioid
      cases (29%), this was not statistically significant. Progesterone receptor
      expression was significantly higher in endometrioid than non-endometrioid cases
      (70% vs. 14%, p<0.05). According to the histological grade: Estrogen and
      progesterone receptors were expressed more frequently in grade I endometrioid
      carcinoma, while p53 was mainly reported in tumor grades II and III. According to
      final disease stage: p53 and estrogen expression in curettage specimens was not
      related to stage; progesterone receptors, however, were expressed significantly
      less in advanced disease. CONCLUSION: p53 was observed in the majority of non
      endometrioid and in high-grade endometrioid carcinoma, but was not related to
      stage. Estrogen and progesterone receptors were mainly found in grade I
      endometrioid carcinoma. The markers studied in curettage were no more valuable
      for predicting the disease stage than classical histological criteria.

PMID- 14595510
TI  - Lung mechanics and high-resolution computed tomography of the chest in very low
      birth weight premature infants.
AB  - CONTEXT: Premature infant lung development may be affected by lung injuries
      during the first few weeks of life. Lung injuries have been associated with
      changes in lung mechanics. OBJECTIVE: To evaluate an association between lung
      mechanics and lung structural alterations in very low birth weight infants (birth
      weight less than 1500 g). DESIGN: A cross-sectional evaluation of pulmonary
      mechanics (lung compliance and lung resistance) and high resolution computed
      tomography of the chest at the time of discharge, in 86 very low birth weight
      infants born at Instituto Fernandes Figueira, a tertiary public healthcare
      institution in Rio de Janeiro, Brazil. Lung compliance and resistance were
      measured during quiet sleep. High resolution computed tomography was performed
      using Pro Speed-S equipment. MAIN MEASUREMENTS: Statistical analysis was
      performed by means of variance analysis (ANOVA/Kruskal Wallis). The significance
      level was set at 0.05. RESULTS: Abnormal values for both lung compliance and lung
      resistance were found in 34 babies (43%), whereas 20 (23.3%) had normal values
      for both lung compliance and lung resistance. The mean lung compliance and lung
      resistance for the group were respectively 1.30 ml/cm H2O/kg and 63.7 cm H2O/l/s.
      Lung alterations were found via high-resolution computed tomography in 62 (72%)
      infants. Most infants showed more than one abnormality, and these were described
      as ground glass opacity, parenchymal bands, atelectasis and bubble/cyst. The mean
      compliance values for infants with normal (1.49 ml/cm H2O/kg) high resolution
      computed tomography, 1 or 2 abnormalities (1.31 ml/cm H2O/kg) and 3 or more
      abnormalities (1.16 ml/cm H2O/kg) were significantly different (p=0.015). Our
      data were insufficient to find any association between lung resistance and the
      number of alterations via high-resolution computed tomography. CONCLUSION: The
      results show high prevalence of lung functional and tomographic abnormalities in
      asymptomatic very low birth weight infants at the time of discharge. They also
      show an association between lung morphological and functional abnormalities.

PMID- 14595511
TI  - Ampullary duodenal diverticulum and cholangitis.
AB  - CONTEXT: Ampullary duodenal diverticulum complicated by cholangitis is little
      known in clinical practice, especially when there are no gallstones in the common
      bile duct or there is no biliary tree ectasia or hyperamylasemia. A case of this
      association is presented, in which the surgical treatment was a biliary-enteric
      bypass. CASE REPORT: A 74-year-old diabetic white woman was admitted to the
      Taubat University Hospital, complaining of pain in the right upper quadrant,
      jaundice and fever with chills (Charcot's triad). She had had cholecystectomy 30
      years earlier. She underwent clinical treatment with parenteral hydration,
      insulin, antibiotics and symptomatic drugs. Imaging examinations were provided
      for diagnosis: ultrasound, computed tomography and endoscopic retrograde
      cholangiopancreatography. The surgical treatment consisted of
      choledochojejunostomy utilizing a Roux-en-y loop. The postoperative period
      progressed without incidents, and a DISIDA scan demonstrated the presence of
      dynamic biliary excretion. The patient remained asymptomatic when seen at
      outpatient follow-up.

PMID- 14595512
TI  - Pfeiffer Syndrome type 2--case report.
AB  - OBJECTIVE: To report on a case of Pfeiffer Syndrome, with a discussion of the
      diagnostic characteristics and features of disease types and the differential
      diagnosis. DESCRIPTION: The authors describe a newborn with cloverleaf skull,
      extreme bilateral exorbitism and choanal atresia, partial syndactyly of the
      second and third toes and broad medially-deviated big toes. The case reported was
      Pfeiffer Syndrome type 2, which usually has a poor prognosis. COMMENTS: Pfeiffer
      Syndrome is a clinically variable disorder and consists of an autosomal
      dominantly-inherited osteochondrodysplasia with craniosynostosis. It has been
      divided into three types. Type 1 is commonly associated with normal intelligence
      and generally good outcome. Types 2 and 3 generally have severe neurological
      compromise, poor prognosis, early death and sporadic occurrence. Potential for
      prolonged useful survival outcome can be achieved in some cases with early
      aggressive medical and surgical management according to recent literature.

PMID- 14595514
TI  - Flavanol binding of nuclei from tree species.
AB  - Light microscopy was used to examine the nuclei of five tree species with respect
      to the presence of flavanols. Flavanols develop a blue colouration in the
      presence of a special p-dimethylaminocinnamaldehyde (DMACA) reagent that enables
      those nuclei loaded with flavanols to be recognized. Staining of the nuclei was
      most pronounced in both Tsuga canadensis and Taxus baccata, variable in
      Metasequoia glyptostroboides, faint in Coffea arabica and minimal in Prunus
      avium. HPLC analysis showed that the five species contained substantial amounts
      of different flavanols such as catechin, epicatechin and proanthocyanidins.
      Quantitatively, total flavanols were quite different among the species. The
      nuclei themselves, as studied in Tsuga seed wings, were found to contain mainly
      catechin, much lower amounts of epicatechin and traces of proanthocyanidins. Blue
      coloured nuclei located centrally in small cells were often found to maximally
      occupy up to 90% of a cell's radius, and the surrounding small rim of cytoplasm
      was visibly free of flavanols. A survey of 34 gymnosperm and angiosperm species
      indicated that the first group has much higher nuclear binding capacities for
      flavanols than the second group.

PMID- 14595515
TI  - Use of asymmetric somatic hybridization for transfer of the bacterial blight
      resistance trait from Oryza meyeriana L. to O. sativa L. ssp. japonica.
AB  - Bacterial blight is one of the major diseases affecting rice productivity. To
      improve the resistance of cultivated rice to bacterial blight, we introduced a
      bacterial blight resistance trait from Oryza meyeriana, a wild rice species, into
      an elite japonica rice cultivar (Dalixiang) using asymmetric somatic
      hybridization. One hundred and thirty-two independent lines were regenerated. The
      hybrid plants possessed several morphological features of the donor species, O.
      meyeriana. Random amplified polymorphic DNA analysis revealed that hybrid plants
      exhibited banding patterns derived from their parental genotypes. For the
      majority of the hybrids, resistance to bacterial blight pathogens was
      intermediate to that observed for O. meyeriana and O. sativa (cv. Dalixiang).
      Four of the hybrid lines exhibited a high bacterial blight resistance, but it was
      less than that observed for O. meyeriana. These results demonstrate that O.
      meyeriana can be used as a good genetic source for improving bacterial blight
      resistance in commercial rice cultivars through asymmetric somatic hybridization.

PMID- 14595516
TI  - Chitosan improves development, and protects Vitis vinifera L. against Botrytis
      cinerea.
AB  - We evaluated the potential of chitosan both to stimulate plant development and to
      induce protection from Botrytis cinerea in Vitis vinifera L. plantlets. The
      presence of 1.75% (v/v) chitogel in the culture medium was the optimal
      concentration for in vitro grapevine plantlet growth, as determined by
      measurements on enhancement of root and shoot biomass. Photosynthesis and related
      parameters were also stimulated in chitogel-treated plantlets. Chitogel reduced
      the development of Botrytis cinerea and induced cytological alterations to the
      pathogen. When challenged with the fungus, a significant decrease in disease
      incidence was observed in plants growing on medium supplemented with chitogel.
      Furthermore, exogenous foliar applications of chitogel to plantlets growing on
      chitogel-free medium sensitized them so as to be protected against Botrytis
      cinerea attack. Our results indicate that chitogel can be used in the vineyard as
      a means to attain protection against Botrytis cinerea and that its application
      may counteract the wide use of chemical pesticides.

PMID- 14595519
TI  - Early escharotomy as a measure to reduce intraabdominal hypertension in full
      thickness burns of the thoracic and abdominal area.
AB  - Intraabdominal hypertension (IAH) can occur in critically ill patients who have
      undergone surgery, who have required fluid resuscitation after intraabdominal
      operations, or whose abdominal surgical wound closure was under tension. If IAH
      remains unrelieved, it can lead to development of the abdominal compartment
      syndrome (ACS). The latter presents with severe cardiorespiratory and urinary
      symptoms such as hypotension, hypoventilation, and oliguria, and it can become
      fatal if it is not diagnosed early and treated properly. Moreover, IAH has been
      documented in the context of major burns, complicating the initial resuscitation
      of these patients. This study was set up to investigate the role of full
      thickness burns of the thoracic and abdominal areas in IAH during the early
      resuscitation period, to determine whether escharotomy could influence its
      levels. During the past 2 years 10 burn patients were enrolled in this study, as
      they fulfilled the necessary criteria: >35% total body surface area (TBSA) full
      thickness burn affecting the anterior, lateral, and most of the posterior surface
      of the thorax and abdomen (torso), no respiratory mechanical support at
      admission, and initial evaluation at another facility and transfer to our burn
      center 2-6 h postburn. Upon admission, the following parameters (indicative of
      intraabdominal hypertension, IAH) were measured: bladder pressure and gastric
      pressure. Also, we monitored inferior vena cava pressure, and as a routine,
      central venous pressure, systolic blood pressure, and arterial blood gases.
      Elevated intraabdominal pressure to hazardous levels was documented in all
      patients included in our study. The same escharotomy pattern was performed in
      every case, and 5-10 min after the procedure all measurements were repeated.
      Immediate improvement of all the parameters measured was recorded, and the
      alterations were found statistically significant. These results were indicative
      of significant relief of the elevated intraabdominal pressure in all patients
      after escharotomy, as well as the efficacy of the procedure. It is thus
      demonstrated that full-thickness burns of the thoracic and abdominal areas can
      cause a significant early increase in intraabdominal pressure that, if left
      untreated, can lead to the development of ACS. However, the application of simple
      decompression techniques can offer remarkable, immediate, and often lifesaving
      results and is absolutely indicated for this reason, as well as for its well
      known beneficial effects on respiratory function.

PMID- 14595518
TI  - The Neurospora crassa mus-19 gene is identical to the qde-3 gene, which encodes a
      RecQ homologue and is involved in recombination repair and postreplication
      repair.
AB  - An allele called mus-19 was identified by screening temperature-sensitive and
      mutagen-sensitive mutants of Neurospora crassa. The mus-19 gene was genetically
      mapped to a region near the end of the right arm of linkage group I, where a RecQ
      homologue called qde-3 had been physically mapped in the Neurospora database.
      Complementation tests between the mus-19 mutant and the qde-3(RIP) mutant showed
      that mus-19 and qde-3 were the same gene. The qde-3 genes of both mutants were
      cloned and sequenced; and the results showed that they have mutation(s) in their
      qde-3 genes. The original mus-19 and qde-3(RIP) mutants are defective in
      quelling, as reported for other qde-3 mutants. The mutants show high sensitivity
      to methyl methanesulfonate, ethyl methanesulfonate, N-methyl- N'-nitro- N
      nitrosoguanidine, tert-butyl hydroperoxide, 4-nitroquinoline-1-oxide, hydroxyurea
      and histidine. Epistasis analysis indicated that the qde-3 gene belongs both to
      the uvs-6 recombination repair pathway and the uvs-2 postreplication repair
      pathway. The qde-3 mutation has no effect on the integration of a plasmid
      carrying the mtr gene by homologous recombination. In homozygous crosses, the qde
      3 mutant is defective in ascospore production.

PMID- 14595517
TI  - KNQ1, a Kluyveromyces lactis gene encoding a drug efflux permease.
AB  - Several transport systems play an important role in conferring multiple drug
      resistance, presumably due to their catalysis of the energy-dependent extrusion
      of a large number of structurally and functionally unrelated compounds out of the
      cells. In the present work, the gene named KNQ1 (encoding Kluyveromyces lactis
      membrane permease) was cloned by functional complementation of the cycloheximide
      hypersensitivity phenotype of the Saccharomyces cerevisiae mutant strain lacking
      a functional PDR5 gene. The isolated gene exhibited 48.9% identity with the S.
      cerevisiae ATR1 gene conferring resistance to aminotriazole and 4-nitroquinoline-
      N-oxide and encoded a protein of 553 amino acids. When present in multicopy, it
      efficiently complemented the phenotype associated with the Delta pdr5 or Delta
      pdr1Delta pdr3 mutations in S. cerevisiae. Overexpression of the KNQ1 gene in K.
      lactis wild-type strains led to resistance against several cytotoxic compounds,
      like 4-nitroquinoline- N-oxide, 3-aminotriazole, bifonazole and ketoconazole. The
      gene was assigned to K. lactis chromosome III and its expression was found to be
      responsive to oxidative stress induced by hydrogen peroxide. Based on the
      phenotype of homologous and heterologous transformants, we propose that the gene
      encodes a membrane-associated component of the machinery responsible for
      decreasing the concentration of several toxic compounds in the cytoplasm of yeast
      cells.

PMID- 14595520
TI  - Modification of mesosigmoidoplasty for nongangrenous sigmoid volvulus.
AB  - Mesosigmoidoplasty is a nonresective procedure for nongangrenous sigmoid
      volvulus. It aims to correct the main pathogenetic factor of this condition, the
      narrow but long mesosigmoid. Although it had been demonstrated by intraoperative
      measurements that this has indeed achieved its purpose, recurrent volvulus has
      been reported after the procedure. This has raised the question of whether an
      operation on the mesosigmoid's peritoneal cover alone is sufficient to maintain
      the change in shape. The modification presented here aims at more sustainable
      shortening and widening of the mesosigmoid by including all its layers in the
      procedure. Of 31 consecutive patients with sigmoid volvulus operated on in Malawi
      in East Africa, 14 had the nongangrenous variety. Twelve of them underwent
      modified mesosigmoidoplasty without any major perioperative complications. There
      was one relaparotomy following misdiagnosis of cryptic Hirschsprung's disease and
      one true recurrence secondary to a technical error during the previous operation.
      During a follow-up of eight patients for 4 to 8 months, there were no complaints
      about abdominal discomfort or changed stool habits. Thus including all layers of
      the mesosigmoid in the plastic procedure did not increase short-term morbidity
      and in theory should be advantageous in respect to preventing recurrence.
      Applying it to a larger series with prolonged follow-up seems to be justified.

PMID- 14595523
TI  - Metabolic engineering for improved fermentation of pentoses by yeasts.
AB  - The fermentation of xylose is essential for the bioconversion of lignocellulose
      to fuels and chemicals, but wild-type strains of Saccharomyces cerevisiae do not
      metabolize xylose, so researchers have engineered xylose metabolism in this
      yeast. Glucose transporters mediate xylose uptake, but no transporter specific
      for xylose has yet been identified. Over-expressing genes for aldose (xylose)
      reductase, xylitol dehydrogenase and moderate levels of xylulokinase enable
      xylose assimilation and fermentation, but a balanced supply of NAD(P) and NAD(P)H
      must be maintained to avoid xylitol production. Reducing production of NADPH by
      blocking the oxidative pentose phosphate cycle can reduce xylitol formation, but
      this occurs at the expense of xylose assimilation. Respiration is critical for
      growth on xylose by both native xylose-fermenting yeasts and recombinant S,
      cerevisiae. Anaerobic growth by recombinant mutants has been reported. Reducing
      the respiration capacity of xylose-metabolizing yeasts increases ethanol
      production. Recently, two routes for arabinose metabolism have been engineered in
      S. cerevisiae and adapted strains of Pichia stipitis have been shown to ferment
      hydrolysates with ethanol yields of 0.45 g g(-1) sugar consumed, so
      commercialization seems feasible for some applications.

PMID- 14595521
TI  - Identification of sentinel lymph nodes in colon cancer depends on the amount of
      dye injected relative to tumor size.
AB  - Recent studies have shown that the sentinel lymph node (SLN) procedure might
      improve staging in colon cancer. However, low SLN identification and high false
      negative rates have also been reported. In a two-institution study, the SLN
      procedure with isosulfan blue 1% was performed according to a standardized
      protocol in 31 patients with open resections for colon cancer. Data were
      collected prospectively. The database was analyzed retrospectively to determine
      factors contributing to a low identification rate. The SLN identification rate
      was 87% and the false negative rate was 50%. Successful SLN identification was
      significantly associated with application of higher volumes of dye relative to
      the tumor diameter ( p = 0.04) and more frequent tumor localization in the
      sigmoid colon ( p = 0.04) as compared to missing SLN identification. The tumor
      diameter was not significantly different in the two groups. Sentinel lymph node
      identification in colon cancer depends on the amount of dye injected relative to
      the tumor size. Application of only 1 ml of dye-the amount generally recommended
      in the literature-is not sufficient in large tumors.

PMID- 14595524
TI  - A thermodynamic interpretation of cell hydrophobicity in aerobic granulation.
AB  - Aerobic granulation can be regarded as a microorganism-to-microorganism self
      immobilization process, in which cell hydrophobicity could be a decisive
      parameter in determining the microorganism-to-microorganism interaction and
      structural compactness of aerobic granules. This study looked into the
      thermodynamic interpretation of cell hydrophobicity in aerobic granulation; and a
      model that correlates microbial interaction and relative cell hydrophobicity
      defined as the ratio of cell hydrophobicity over cell hydrophilicity was derived.
      This model describes how cell hydrophobic and hydrophilic interactions affect
      aerobic granulation and offers deep insights into the thermodynamic mechanisms of
      microbial aggregation. The model prediction was in good agreement with
      experimental data. Results showed that aerobic granulation was a function of cell
      hydrophobicity over cell hydrophilicity, i.e. a high cell hydrophobicity strongly
      favors microbial aggregation and results in a more compact structure.

PMID- 14595525
TI  - Identification of a type-D feruloyl esterase from Neurospora crassa.
AB  - Feruloyl esterases constitute an interesting group of enzymes that have the
      potential for use over a broad range of applications in the agri-food industries.
      In order to expand the range of available enzymes, we have examined the presence
      of feruoyl esterase genes present in the genome sequence of the filamentous
      fungus Neurospora crassa. We have identified an orphan gene (contig 3.544), the
      translation of which shows sequence identity with known feruloyl esterases. This
      gene was cloned and the corresponding recombinant protein expressed in Pichia
      pastoris to confirm that the enzyme (NcFaeD-3.544) exhibits feruloyl esterase
      activity. Unusually the enzyme was capable of p-coumaric acid release from
      untreated crude plant cell wall materials. The substrate utilisation preferences
      of the recombinant enzyme place it in the recently recognised type-D sub-class of
      feruloyl esterase.

PMID- 14595528
TI  - Association of the collagen type 1 (COL1A 1) Sp1 binding site polymorphism to
      femoral neck bone mineral density and wrist fracture in 1044 elderly Swedish
      women.
AB  - Identification of risk factors for osteoporosis has been essential for
      understanding the development of osteoporosis and related fragility fractures. A
      polymorphism of the binding site for the transcription factor Sp1 of the collagen
      I alpha 1 gene (COLIA1) has shown an association to bone mass and fracture, but
      the findings have not been consistent, which may be related to population
      differences. The Sp1 polymorphism was determined in 1044 women, all 75 years old,
      participating in the population-based Osteoporosis Prospective Risk Assessment
      study in Malmo (OPRA). Bone mineral density, heel ultrasound and all previous
      fractures were registered. BMD was 2.7% lower in the femoral neck in women
      carrying at least one copy of the "s" allele ( P = 0.027). There was no
      difference in bone mass at any other site, weight, BMI or age at menopause. Women
      with a prevalent wrist fracture (n = 181) had an increased presence of the "s"
      allele. The odds ratio for prevalent wrist fracture was 2.73 (95% CI 1.1-6.8) for
      the ss homozygotes and 1.4 (95% CI 1.0-2.0) for the Ss heterozygotes when
      compared with the SS homozygotes. In conclusion, in this large and homogeneous
      cohort of 75-year-old Swedish women, there was an association among the Sp1
      COLIA1 polymorphism, bone mass, and fracture. The presence of at least one copy
      of the "s" allele was associated with lower femoral neck BMD and previous wrist
      fracture and in addition, it was related to an increased risk for wrist fracture.

PMID- 14595529
TI  - Cbfa1/osf2 transduced bone marrow stromal cells facilitate bone formation in
      vitro and in vivo.
AB  - It has been well established that core binding factor a-1/osteoblast-specific
      factor-2 (cbfa1/osf2) is a key regulator of osteoblast differentiation and
      function, however, it is not known whether it can induce bone formation in vitro
      and in vivo. To investigate the effect of cbfa1/osf2 on bone formation, we used a
      recombinant adenoviral vector carrying the mouse cbfa1/osf2 gene to transduce
      primary cultured bone marrow stromal cells (MSCs) of BALB/c mice. We found that
      Ad-cbfa1/osf2-transduced MSCs produced cbfa1/osf2 protein and differentiated into
      osteoblast-like cells. The transduced MSCs had increased alkaline phosphatase
      activity, increased expression of osteocalcin, osteopontin and bone sialoprotein,
      and increased matrix mineralization in vitro. To observe the induction of bone
      formation in vivo, MSCs transduced with Ad-cbfa1/osf2 were transplanted into a 5
      mm diameter critical-sized skull defect in BALB/c mice, with type I collagen as
      scaffolding material. Healing of the defect in treatment and control groups was
      examined grossly and histologically at four weeks. Skull defects transplanted
      with Ad-cbfa1/osf2-transduced MSCs had an average of 85% osseous closure at four
      weeks. Control groups in which the defects were not treated (group 1), treated
      with collagen only (group 2), or treated with collagen and nontransduced MSCs
      (group 3) showed little or no osseous healing. These studies indicate that
      cbfa1/osf2 can induce osteoblast differentiation and bone formation both in vitro
      and in vivo, suggesting that MSCs transduced with the cbfa1/osf2 gene may be
      useful in treating bone defects.

PMID- 14595527
TI  - Controlled withdrawal of selective serotonin reuptake inhibitor drugs in elderly
      patients in nursing homes with no indication of depression.
AB  - OBJECTIVE: The aim of the investigation was to study the effects of withdrawing
      selective serotonin reuptake inhibitor (SSRI) drugs in nursing home patients, who
      had no documented diagnosis or symptoms of depression. SETTING: The setting of
      the study was in 11 nursing homes in the county of Stockholm, Sweden.
      PARTICIPANTS: Participants were patients without dementia or history of
      depression who had received treatment with SSRI drugs for more than 6 months and
      who had no indications of anxiety disorder or major depression DESIGN: The
      included patients ( n=70) were randomized to either the intervention group
      (withdrawal of SSRI) or the control group (no change in treatment), 35 patients
      to each group. MAIN OUTCOME MEASURES: The patients were subjected to assessment
      using the following instruments: Montgomery-Asberg depression rating scale,
      global assessment for functioning, health index and a symptom assessment form.
      Assessment was made at the start of the study and at the 3-month and 6-month
      follow-ups. RESULTS: We found no significant difference between the intervention
      and control groups in any outcome measure. CONCLUSION: Treatment with SSRI drugs
      in patients without clinical major depression or anxiety disorder is often
      unjustified and should be discontinued.

PMID- 14595530
TI  - Gene expression for extracellular matrix proteins in shockwave-induced
      osteogenesis in rats.
AB  - To clarify the mechanisms underlying shockwave-induced osteogenesis, we applied
      shockwave to rat femoral shafts from the ventral side. We assessed bone mineral
      content (BMC) and bone mineral density (BMD), and analyzed the spatial and
      temporal gene expression for pro-alpha1 (I) collagen (COL1A1), pro-alpha1 (II)
      collagen (COL2A1), pro-alpha1 (X) collagen (COL10A1), osteocalcin (OC) and
      osteopontin (OPN) using in situ hybridization. On the 21st day post-exposure, BMC
      and BMD in the exposed femur were elevated by 8.46% and 5.80%, respectively,
      relative to the unexposed femur. Immediately following exposure, there was
      evidence of scraping of the cortex and periosteal separation with hemorrhage. On
      day 4, new periosteal bone formation could be seen on the ventral and dorsal side
      of the femur. In the newly formed bone, COL1A1, OC and OPN were expressed in
      osteoblastic cells underlying the periosteum. On day 7, there was progression of
      periosteal bone and trabeculae formation. COL1A1 and OC were expressed in mature
      osteoblasts lining the trabeculae, whereas OPN was expressed in immature
      osteoblastic cells, osteocytes and osteoclasts. On day 14, bone remodeling
      commenced in the periosteal bone. COL1A1, OC and OPN were still expressed at this
      stage, however, signals were much weaker. Between 4-7 days, chondrocyte clusters
      were distributed multi-focally near the exposed site, and there was expression of
      COL2A1 but not of COL10A1. The results demonstrate that gene expression patterns
      of shockwave-induced osteogenesis are similar to those of periosteal hard callus
      formation during fracture healing. Shockwaves can yield dramatic activation of
      cells in normal long bones, and drive the cells to express genes for
      osteogenesis.

PMID- 14595531
TI  - Association of estrogen receptor alpha and vitamin D receptor gene polymorphisms
      with bone mineral density in Chinese males.
AB  - Osteoporosis is a common health problem not only in females but also in males,
      however, studies of osteoporosis in males are relatively rare compared to those
      in females. This is especially true in genetics studies. We evaluated the effects
      of PvuII and XbaI polymorphisms in the estrogen receptor alpha (ER-alpha) gene
      and ApaI polymorphism in the vitamin D receptor (VDR) gene on BMD variation in a
      random sample of 352 unrelated males from 401 Chinese nuclear families. BMD was
      measured at the lumbar spine (L1-L4) and hip (femoral neck, trochanter,
      intertrochanteric region). Raw BMD values were adjusted by age, age(2), height,
      and weight as covariates. We found no significant results for the 3 individual
      markers on BMD variation, however, ER-alpha haplotype analyses yielded some
      interesting results. Carriers of haplotype pX had a 4.98% lower BMD at the
      trochanter (P = 0.02) and 3.55% lower BMD at the lumbar spine (P = 0.09) than non
      carriers. PX subjects had a 3.42% higher BMD at the trochanter and 3.26% higher
      BMD at the lumbar spine than others (P = 0.07 and P = 0.10, respectively). Such
      results were highly comparable with the significant or nearly significant
      interactions between ER-PvuII and ER-XbaI on BMD values at the trochanter (P =
      0.03) and spine (P = 0.11). No significant results were observed for the
      interactions between ER-PvuII and VDR-ApaI, between ER-XbaI and VDR-ApaI, and
      between any of ER-alpha haplotypes and VDR-ApaI locus. Our results suggest that
      the ER-alpha haplotypes, not individual markers, may be associated with BMD
      variation at some skeletal sites in our Chinese male samples.

PMID- 14595535
TI  - Effects of chronic exposure to cadmium on renal cytochrome P450-dependent
      monooxygenase system in rats.
AB  - The aim of this study was to evaluate the effects of chronic exposure to cadmium
      (Cd) on the renal cytochrome P450-dependent monooxygenase system. For this
      purpose, male Wistar rats were intoxicated with Cd administered in drinking water
      at a concentration of 5 or 50 mg Cd/l for 6, 12 and 24 weeks. Concentrations of
      cytochrome P450 and cytochrome b(5) as well as activities of NADPH-cytochrome
      P450 reductase and NADH-cytochrome b(5) reductase were determined in the kidney
      microsomal fraction. Protein content of CYP1A1, CYP2E1 and CYP3A1 cytochrome P450
      isoforms was evaluated as well. In the rats exposed to 5 mg Cd/l, the
      concentration of cytochrome P450 decreased (by 41%) after 24 weeks of the
      experiment. The activity of NADPH-cytochrome P450 reductase decreased (by 24%)
      after 6 and 12 weeks, whereas after 24 weeks it remained unchanged, compared with
      the control group. Moreover, a decrease in the concentration of cytochrome b(5)
      (by 25, 15 and 26% at 6, 12 and 24 weeks, respectively) and the activity of its
      NADH reductase (by 26 and 31% at 6 and 24 weeks, respectively) was noted in these
      animals. At the exposure to 50 mg Cd/l, the concentrations of cytochrome P450 and
      cytochrome b(5) and the activities of their corresponding reductases were
      decreased at each time-point. Western blot analysis revealed that all isoforms of
      cytochrome P450 studied were affected by Cd and the effect was dependent on the
      level and the duration of exposure. The results of this study indicate that
      chronic exposure to Cd in a dose- and time-dependent manner affects the kidney
      cytochrome P450-dependent monooxygenase system by decreasing the concentrations
      of cytochrome P450 and cytochrome b(5) and inhibiting the activities of their
      corresponding reductases. The effect of Cd on the cytochrome P450 content is
      associated with its ability to stimulate or inhibit of various P450 isoforms. A
      very important finding of this study is that Cd affects the kidney cytochrome
      P450-dependent monooxygenase system at relatively low exposure and low kidney Cd
      accumulation (2.40+/-0.15 microg/g). As the experimental model used reflects
      human exposure to Cd, we conclude that Cd can affect the kidney cytochrome P450
      dependent monooxygenase system in environmentally exposed humans. Previously we
      have reported disorders in the system in the liver of rats at the same levels of
      exposure as in this study. Thus, we hypothesize that the metabolism and
      detoxification of many substances, including xenobiotics, may be seriously
      affected in Cd-exposed subjects.

PMID- 14595536
TI  - Compression of the suprascapular nerve by a ganglion cyst of the spinoglenoid
      notch: the arthroscopic solution.
AB  - We evaluated an all arthroscopic technique for treating suprascapular nerve
      entrapment by cyst formation in the spinoglenoid notch. Eight patients showed
      positive MRI and EMG findings with clinical sign of weakness and pain and with
      atrophy of the muscle. All patients underwent an all-arthroscopic procedure. The
      patients were evaluated preoperatively and 6 weeks and 3 months postoperatively
      and for the latest follow-up by clinical examination, MRI, and EMG. All patients
      improved in terms of pain, strength, and function. We found six superior labrum
      anterior and posterior (SLAP) lesions. In these patients the cyst was drained,
      and the SLAP lesion was repaired. In two patients there was no communication
      between the joint and the cyst, and therefore capsulotomy was performed and left
      open. The results of our study show that arthroscopic decompression of the
      suprascapular nerve can be achieved by an all arthroscopic technique if the cyst
      formation is located at the spinoglenoid notch.

PMID- 14595537
TI  - To: Rippin JD, Patel A, Belyaev ND, Gill GV, Barnett AH, Bain SC (2003) Nitric
      oxide synthase gene polymorphisms and diabetic nephropathy. Diabetologia 46:426
      428.

PMID- 14595538
TI  - Type 2 diabetes and atrophy of medial temporal lobe structures on brain MRI.
AB  - AIM/HYPOTHESIS: Type 2 diabetes increases the risk not only of vascular dementia
      but also of Alzheimer's disease. The question remains whether diabetes increases
      the risk of Alzheimer's disease by diabetic vasculopathy or whether diabetes
      influences directly the development of Alzheimer neuropathology. In vivo,
      hippocampal and amygdalar atrophy on brain MRI are good, early markers of the
      degree of Alzheimer neuropathology. We investigated the association between
      diabetes mellitus, insulin resistance and the degree of hippocampal and amygdalar
      atrophy on magnetic resonance imaging (MRI) accounting for vascular pathology.
      METHODS: Data was obtained in a population-based study of elderly subjects
      without dementia between 60 to 90 years of age. The presence of diabetes mellitus
      and, in non-diabetic subjects, insulin resistance was assessed for 506
      participants in whom hippocampal and amygdalar volumes on MRI were measured. We
      assessed the degree of vascular morbidity by rating carotid atherosclerosis, and
      brain white matter lesions and infarcts on MRI. RESULTS: Subjects with diabetes
      mellitus had more hippocampal and amygdalar atrophy on MRI compared to subjects
      without diabetes mellitus. Furthermore, increasing insulin resistance was
      associated with more amygdalar atrophy on MRI. The associations were not due to
      vascular morbidity being more pronounced in persons with diabetes mellitus.
      CONCLUSIONS/INTERPRETATION: Type 2 diabetes is associated with hippocampal and
      amygdalar atrophy, regardless of vascular pathology. This could suggest that Type
      2 diabetes directly influences the development of Alzheimer neuropathology.

PMID- 14595540
TI  - The diabetes prone BB rat model of IDDM shows duration of breastfeeding to
      influence Type 1 diabetes development later in life.

PMID- 14595541
TI  - Absence of association between SPINK1 trypsin inhibitor mutations and Type 1 or 2
      diabetes mellitus in India and Germany.

PMID- 14595539
TI  - Rosiglitazone produces insulin sensitisation by increasing expression of the
      insulin receptor and its tyrosine kinase activity in brown adipocytes.
AB  - AIMS/HYPOTHESIS: Rosiglitazone is used to treat Type 2 diabetes because it
      improves insulin sensitivity. However, the specific molecular mechanism by which
      this compound acts has not yet been explained. METHODS: We used fetal rat primary
      brown adipocytes cultured for 24 h with or without 10 micro mol/l rosiglitazone
      and further stimulated for 5 min with 10 nmol/l insulin. Next we measured glucose
      uptake and GLUT4 translocation and submitted the cells to lysis,
      immunoprecipitation and immunoblotting in order to measure the insulin signalling
      cascade. RESULTS: Rosiglitazone noticeably activated basal glucose uptake in a
      manner dependent on p38-mitogen-activated protein kinase. Rosiglitazone also
      produced a 40% increase in insulin-stimulated glucose uptake as a result of
      increased GLUT4 translocation to the plasma membrane. This happened without
      changes in the expression of GLUT4 at the mRNA or protein level. This effect
      correlated with the potentiation by rosiglitazone of insulin-stimulated Tyr
      phosphorylation of insulin receptor substrate-1 and to a greater extent of
      insulin receptor substrate-2. It also correlated with the subsequent activation
      of phosphatidylinositol 3-kinase and Akt, without changes in protein kinase Czeta
      activity. Rosiglitazone treatment increased insulin receptor expression and
      insulin-stimulated Tyr phosphorylation of insulin receptor beta-chain, but
      decreased insulin-stimulated Ser phosphorylation. It also potentiated insulin
      induced Tyr phosphorylation of insulin receptor beta-chain and protein tyrosine
      phosphatase 1B in co-immunoprecipitates and impaired insulin activation of
      protein tyrosine phosphatase 1B activity. CONCLUSIONS/INTERPRETATION: At the
      insulin receptor level, rosiglitazone-induced improvements of insulin sensitivity
      result from two convergent mechanisms: increased insulin receptor expression and
      insulin receptor activation.

PMID- 14595543
TI  - The genetic diversity of cultivated soybean grown in China.
AB  - Cultivated soybean ( Glycine max) is an economically important crop that is grown
      for its oil and protein products. A better knowledge of its genetic diversity
      will be valuable for the utilization, conservation, and management of germplasm
      collections. Using the database of the National Germplasm Evaluation Program of
      China (NGEPC), we studied the geographical distribution of accessions, the
      genetic diversity of 15 qualitative and quantitative characters, and the genetic
      diversity centers of cultivated soybean in China using variation in these 15
      traits and genetic diversity indexes (Shannon index). Cultivated soybean is
      widely distributed throughout China. As an indication of its distribution, a line
      can be roughly drawn from the Daxinganling mountains in northeastern China to the
      Qingzang plateaus in southwestern China based on the abundance of accessions and
      locations of the collections. Of the 22,637 known accessions in China, the 20,570
      collected over a vast area between latitudes 18 degrees and 53 degrees N and
      longitudes 80 degrees and 136 degrees E were used in this study. The Shannon
      indexes of various morphological traits were calculated. Cultivated soybean
      accessions were found to exhibit a higher genetic diversity in the area between
      34 degrees -41 degrees N and 110 degrees -115 degrees E. On the basis of the
      geographical distribution of a number of accessions, and their genetic diversity,
      one genetic diversity center-downstream of the Yellow River Valley-is proposed.
      Based on these results and on Vavilov's theory on crop origins, one possible
      diversity center was proposed.

PMID- 14595542
TI  - Oleate, not ligands of the receptor for advanced glycation end-products, promotes
      proliferation of human arterial smooth muscle cells.
AB  - AIMS/HYPOTHESIS: Diabetes accelerates cardiovascular disease caused by
      atherosclerosis. Accordingly, diabetes accelerates atherosclerotic lesion
      progression and increases arterial smooth muscle cell proliferation. We
      hypothesized that diabetes can exert growth-promoting effects on smooth muscle
      cells via increased advanced glycation end-products or by dyslipidaemia. METHODS:
      Primary human arterial smooth muscle cells were stimulated with advanced
      glycation end-products, other ligands of the receptor for advanced glycation end
      products or fatty acids common in triglycerides. Cell proliferation was measured
      as DNA synthesis, cell cycle distribution and cell number. Effects of oleate on
      cellular phospholipids, diacylglycerol, triglycerides and cholesterol esters were
      analyzed by thin-layer chromatography, and oleate accumulation into
      diacylglycerol was confirmed by gas chromatography. RESULTS: Human arterial
      smooth muscle cells express the receptor for advanced glycation end-products, but
      its ligands N(epsilon)-(carboxymethyl)lysine-modified proteins, methylglyoxal
      modified proteins, S100B polypeptide and amyloid-beta (1-40) peptide, exert no
      mitogenic action. Instead, oleate, one of the most common fatty acids in
      triglycerides, enhances platelet-derived growth factor-BB-mediated proliferation
      and oleate-containing 1,2-diacylglycerol formation in smooth muscle cells. This
      mitogenic effect of oleate depends on phospholipase D activity and is associated
      with an increased formation of oleate-enriched 1,2-diacylglycerol.
      CONCLUSION/INTERPRETATION: Oleate, not ligands of the receptor for advanced
      glycation end-products, acts as an enhancer of human smooth muscle cell
      proliferation. Thus, lipid abnormalities, rather than hyperglycaemia, could be a
      major factor promoting proliferation of smooth muscle cells in atherosclerotic
      lesions.

PMID- 14595544
TI  - Computer-integrated finite element modeling of human middle ear.
AB  - The objective of this study was to produce an improved finite element (FE) model
      of the human middle ear and to compare the model with human data. We began with a
      systematic and accurate geometric modeling technique for reconstructing the
      middle ear from serial sections of a freshly frozen temporal bone. A geometric
      model of a human middle ear was constructed in a computer-aided design (CAD)
      environment with particular attention to geometry and microanatomy. Using the
      geometric model, a working FE model of the human middle ear was created using
      previously published material properties of middle ear components. This working
      FE model was finalized by a cross-calibration technique, comparing its predicted
      stapes footplate displacements with laser Doppler interferometry measurements
      from fresh temporal bones. The final FE model was shown to be reasonable in
      predicting the ossicular mechanics of the human middle ear.

PMID- 14595545
TI  - Modeling 3-D deformation of outer hair cells and their production of the active
      force in the cochlea.
AB  - We analyze the deformation of the outer hair cell and its production of active
      force under physiological conditions. The active force has two components. One
      results from the strain caused by loading in the organ of Corti in the cochlea
      and depends on the level of the acoustic signal; the other is related to the
      intrinsic active properties of the cell membrane. We demonstrate our approach by
      considering, as a basic model of an outer hair cell in the organ of Corti, a
      cylindrical shell that is filled with an incompressible fluid and located between
      two planes that move relative to each other. These planes represent the basilar
      membrane and tectorial membrane complexes. We show that the deformed state of the
      cell has a 3-D nature, including bending and twisting components. This is
      different from the experimental conditions in which the active force is usually
      measured. We estimate the active force as a function of the relative position of
      the planes, angle of the cell's inclination, and the cell length.

PMID- 14595546
TI  - Temperature difference between the body core and arterial blood supplied to the
      brain during hyperthermia or hypothermia in humans.
AB  - Avascular heat transfer model is developed to simulate temperature decay along
      the carotid arteries in humans, and thus, to evaluate temperature differences
      between the body core and arterial blood supplied to the brain. Included are
      several factors, including the local blood perfusion rate, blood vessel
      bifurcation in the neck, and blood vessel pairs on both sides of the neck. The
      potential for cooling blood in the carotid artery by countercurrent heat exchange
      with the jugular veins and by radial heat conduction to the neck surface was
      estimated. Cooling along the common and internal carotid arteries was calculated
      to be up to 0.87 degrees C during hyperthermia by high environmental temperatures
      or muscular exercise. This model was also used to evaluate the feasibility of
      lowering the brain temperature effectively by placing ice pads on the neck and
      head surface or by wearing cooling garments during hypothermia treatment for
      brain injury or other medical conditions. It was found that a 1.1 degrees C
      temperature drop along the carotid arteries is possible when the neck surface is
      cooled to 0 degrees C. Thus, the body core temperature may not be a good
      indication of the brain temperature during hyperthermia or hypothermia.

PMID- 14595547
TI  - Brain mechanics For neurosurgery: modeling issues.
AB  - Brain biomechanics has been investigated for more than 30 years. In particular,
      finite element analyses and other powerful computational methods have long been
      used to provide quantitative results in the investigation of dynamic processes
      such as head trauma. Nevertheless, the potential of these methods to simulate and
      predict the outcome of quasi-static processes such as neurosurgical procedures
      and neuropathological processes has only recently been explored. Some inherent
      difficulties in modeling brain tissues, which have impeded progress, are
      discussed in this work. The behavior of viscoelastic and poroelastic constitutive
      models is compared in simple 1-D simulations using the ABAQUS finite element
      platform. In addition, the behaviors of quasi-static brain constitutive models
      that have recently been proposed are compared. We conclude that a compressible
      viscoelastic solid model may be the most appropriate for modeling neurosurgical
      procedures.

PMID- 14595548
TI  - Investigation of bovine bone by resonant ultrasound spectroscopy and transmission
      ultrasound.
AB  - The method of resonant ultrasonic spectroscopy (RUS) was evaluated for bovine
      bone and compared with the traditional wave transmission ultrasound method. In
      RUS, the resonance structure of a cubic or rectangular specimen is scanned. For
      some low-damping materials, a single measurement yields sufficient resonant
      frequencies to determine all of the anisotropic elastic constants. Bone has a
      high viscoelastic damping at ultrasonic frequency. Consequently, resonance peaks
      of a cubic specimen tend to overlap. Therefore, the usual RUS method must be
      modified for application to bone; even so, one cannot obtain all the elastic
      constants. Concurrent studies with transmission ultrasound were conducted.
      Results were used to generate a map of the elastic moduli vs position along the
      bone axis. Stiffness was greatest in the mid part of the bovine femur.

PMID- 14595549
TI  - Genetic variability assessed by microsatellites in a breeding program of Pacific
      white shrimp (Litopenaeus vannamei).
AB  - Genetic diversity in a shrimp-breeding program was monitored for 2 generations by
      microsatellite DNA markers (Pvan1578 and Pvan1815) to establish levels of
      variation and proceed with a selection program. An increase in the number and
      frequencies of some alleles in both microsatellite loci from G0 to G2 was induced
      by foreign sire contributions. Most common alleles and high heterozygosities
      (around 70% in both loci) were maintained through the generations, indicating
      that there had not been a significant loss of genetic variability in the breeding
      program. However, when compared with variability in other wild and cultured
      stocks, the presence of 4 main alleles at both loci may be an indication that a
      certain reduction in variability already was present in the line used as founder
      stock (G0). Therefore, it is recommended that additional genetic variability be
      introduced to the breeding stock by crossing it with a different line.

PMID- 14595550
TI  - Expressed sequence tag analysis of vanadocytes in a vanadium-rich ascidian,
      Ascidia sydneiensis samea.
AB  - Some species in the family Ascidiidae accumulate vanadium at concentrations in
      excess of 350 mM, which corresponds to about 10(7) times higher than that in
      seawater. In these species signet ring cells, with a single huge vacuole in which
      vanadium ion is contained, function as vanadium-accumulating cells, vanadocytes.
      To investigate the mechanism underlying this phenomenon, we performed an
      expressed sequence tag (EST) analysis of a complementary DNA library from
      vanadocytes of a vanadium-rich ascidian, Ascidia sydneiensis samea. We determined
      the nucleotide sequences of 1000 ESTs and performed a BLAST analysis against the
      SwissProt database. We found 93 clones of metal-related gene homologues,
      including the ferritin heavy subunit, hemocyanin, and metallothionein. Two ESTs,
      in particular, exhibited significant similarity to vanabins that have been
      extracted from A. sydneiensis samea blood cells as low molecular weight vanadium
      binding proteins. We have named the genes encoding these ESTs vanabin3 and
      vanabin4. Immobilized metal ion affinity chromatography revealed that these novel
      vanabin homologues bind vanadium(IV) ions.

PMID- 14595554
TI  - Invasion rates increase with species richness in a marine epibenthic community by
      two mechanisms.
AB  - It is widely believed that, when extrinsic conditions are similar, the likelihood
      of species invading established assemblages decreases with increasing species
      richness of the recipient community. Here we show that, for a sessile marine
      invertebrate community, invasion of patches increases with richness of the patch.
      We show that invasions can increase with local species richness by two distinct
      mechanisms. In the first, opportunistic colonisers with traits typical of
      invasive species colonise species-rich patches at higher rates because speciose
      patches are dominated by small colonies and mortality rates of small colonies are
      greater than that of large ones. Thus, mortality provides bare space for
      opportunists to colonise more frequently in species-rich patches. In the second,
      some species avoid colonising open areas of free space but preferentially
      associate with established colonies of particular other species, and a given
      preferred associate is more likely to occur in species-rich than in species-poor
      patches. These patterns are the result of particular properties of individual
      species and local species dynamics, and show that reduced risk of invasion is not
      necessarily an intrinsic property of species-rich communities. We conclude that
      resistance to invasion will be determined by the properties of the particular
      component species and emergent dynamics of the recipient community, and not by an
      aggregate community property such as richness.

PMID- 14595552
TI  - Investigation of seven proposed regions of linkage in multiple sclerosis: an
      American and French collaborative study.
AB  - Multiple sclerosis (MS) is a demyelinating autoimmune disease with a strong yet
      complex genetic component. To date only the HLA-DR locus, and specifically the
      HLA-DR15 allele, has been identified and confirmed as influencing the risk of
      developing MS. Genomic screens on several datasets have been performed and have
      identified several chromosomal regions with interesting results, but none have
      yet been confirmed. We tested seven of the most-promising regions (on chromosomes
      1p, 2p, 3p, 3q, 5q, 19q, and Xp) identified from several genomic screens in a
      dataset of 98 multiplex MS families from the United States and 90 multiplex MS
      families from France. The results did not confirm linkage to 2p, 3q, 5q, or Xp in
      the overall dataset, or in subsets defined by geographic origin or HLA-DR15
      status. Regions on 1p34, 3p14, and 19q13 produced lod scores >0.90 in at least
      one subset of the data, suggesting that these regions should be examined in more
      detail.

PMID- 14595555
TI  - Using stable isotopes to investigate migratory connectivity of the globally
      threatened aquatic warbler Acrocephalus paludicola.
AB  - Understanding the links between breeding and wintering areas of migratory species
      has important ecological and conservation implications. Recently, stable isotope
      technology has been used to further our understanding. Stable isotope ratios vary
      geographically with a range of biogeochemical factors and isotope profiles in
      organisms reflect those in their food and environment. For inert tissues like
      feathers, isotope profiles reflect the environment in which they were formed.
      Following large-scale habitat destruction, the globally threatened aquatic
      warbler Acrocephalus paludicola has a fragmented breeding population across
      central Europe, largely in Belarus, Poland and Ukraine. The species' sub-Saharan
      African wintering grounds have not yet been discovered, and this significantly
      hampers conservation efforts. Aquatic warblers grow their flight feathers on
      their wintering grounds, and we analysed stable isotope ratios (delta(15)N,
      delta(13)C, delta D) in rectrices of adults from six main breeding sites
      (subpopulations) across Europe to determine whether different breeding
      subpopulations formed a single mixed population on the wintering grounds.
      delta(15)N varies considerably with dietary trophic level and environmental
      factors, and delta D with the delta D in rainfall; neither varied between aquatic
      warbler subpopulations. Uniform feather delta(15)N signatures suggest no major
      variation in dietary trophic level during feather formation. High variance and
      inter-annual differences in mean delta D values hinder interpretation of these
      data. Significant differences in mean delta(13)C ratios existed between
      subpopulations. We discuss possible interpretations of this result, and consider
      differences in moulting latitude of different subpopulations to be the most
      parsimonious. delta(13)C in plants and animals decreases with latitude, along a
      steep gradient in sub-Saharan Africa. Birds from the most northwesterly breeding
      subpopulation (Karsibor, Poland) had significantly lower variance in delta(13)C
      and delta(15)N than birds from all other sites, suggesting either that birds from
      Karsibor are less geographically dispersed during moult, or moult in an area with
      less isotopic heterogeneity. Mean delta(13)C signatures from winter-grown
      feathers of different subpopulations were positively correlated with the latitude
      and longitude of breeding sites, suggesting a strong relationship between
      European breeding and African winter moulting latitudes. The use of stable
      isotopes provides novel insights into migratory connectivity and migration
      patterns in this little-known threatened species.

PMID- 14595557
TI  - Discrimination of homoeologous gene expression in hexaploid wheat by SNP analysis
      of contigs grouped from a large number of expressed sequence tags.
AB  - Single-nucleotide polymorphisms (SNPs) are useful markers for gene diagnosis and
      mapping of genes on chromosomes. However, polyploidy, which is characteristic of
      the evolution of higher plants, complicates the analysis of SNPs in the
      duplicated genes. We have developed a new method for SNP analysis in hexaploid
      wheat. First, we classified a large number of expressed sequence tags (ESTs) from
      wheat in silico. Those grouped into contigs were anticipated to correspond to
      transcripts from homoeologous loci. We then selected relatively abundant ESTs,
      and assigned these contigs to each of the homoeologous chromosomes using a
      nullisomic/tetrasomic series of Chinese Spring wheat strains in combination with
      pyrosequencing. The ninety genes assigned were almost evenly distributed into
      seven homologous chromosomes. We then created a virtual display of the relative
      expression of these genes. Expression patterns of genes from the three genomes in
      hexaploid wheat were classified into two major groups: (1) genes almost equally
      expressed from all three genomes; and (2) genes expressed with a significant
      preference, which changed from tissue to tissue, from certain genomes. In 11
      cases, one of the three genes in the allopolyploid was found to be silenced. No
      preference for gene-silencing in particular genomes or chromosomes was observed,
      suggesting that gene-silencing occurred after polyploidization, and at the gene
      level, not at the chromosome or genome level. Thus, the use of this SNP method to
      distinguish the expression profiles of three homoeologous genes may help to
      elucidate the molecular basis of heterosis in polyploid plants.

PMID- 14595556
TI  - Naturally mosaic operons for secondary metabolite biosynthesis: variability and
      putative horizontal transfer of discrete catalytic domains of the epothilone
      polyketide synthase locus.
AB  - A putative instance of horizontal gene transfer (HGT) involving adjacent,
      discrete beta-ketoacyl synthase (KS), acyl carrier protein (ACP) and nonribosomal
      peptide synthase (NRPS) domains of the epothilone Type I polyketide biosynthetic
      gene cluster from the myxobacterium Sorangium cellulosom was identified using
      molecular phylogenetics and sequence analyses. The specific KS domain of the
      module EPO B fails to cluster phylogenetically with other epothilone KS sequences
      present at this locus, in contrast to what is typically observed in many other
      Type I polyketide synthase (PKS) biosynthetic loci. Furthermore, the GC content
      of the epoB KS, epoA ACP and NRPS domains differs significantly from the base
      composition of other epothilone domain sequences. In addition, the putatively
      transferred epothilone loci are located near previously identified transposon
      like sequences. Lastly, comparison with other KS loci revealed another possible
      case of horizontal transfer of secondary metabolite genes in the genus
      Pseudomonas. This study emphasizes the use of several lines of concordant
      evidence (phylogenetics, base composition, transposon sequences) to infer the
      evolutionary history of particular gene and enzyme sequences, and the results
      support the idea that genes coding for adaptive traits, e.g. defensive natural
      products, may be prone to transposition between divergent prokaryotic taxa and
      genomes.

PMID- 14595558
TI  - Health economic issues of screening programmes.
AB  - Economic evaluation supports decision making in health care in view of
      alternative courses of action and limited resources. It aims at providing maximum
      benefit in relation to invested resources. In the context of screening, it is
      required from an economical viewpoint that the cost of case finding, including
      confirmatory diagnostic tests and treatment, should be economically balanced in
      relation to possible expenditure on medical care as a whole. Costs of false
      positive findings are crucial in newborn screening and pertain to direct costs
      (e.g. necessary diagnostic work-up), indirect costs (e.g. absence from work of
      parents) and intangible costs (e.g. anxiety and distress caused, stigmatisation).

PMID- 14595559
TI  - Transformation of myocarditis and inflammatory cardiomyopathy to idiopathic
      dilated cardiomyopathy: facts and fiction.
AB  - There is broad evidence that enteroviruses and adenoviruses can induce an acute
      inflammation of the myocardium without cardiac dysfunction (i.e. myocarditis) or
      with cardiac dysfunction (i.e. inflammatory cardiomyopathy) that can transform to
      a virus-negative dilated cardiomyopathy. In the adult patient neither other
      viruses (parvo-B 19 virus, hepatitis C virus, cytomegalovirus) nor post-infection
      autoimmunity are likely to induce idiopathic dilated cardiomyopathy.

PMID- 14595560
TI  - Variable action effects: response control by context-specific effect
      anticipations.
AB  - The ideomotor principle (IMP) claims that bidirectional associations between
      actions and their contingent effects are acquired so that voluntary actions are
      accessed by the anticipation of intended effects. Until now, evidence for the IMP
      exists only for stable action-effect relations. The present paper explores
      whether the IMP also holds true for the initiation of actions for which no
      unconditional contingent action-effect relations exist. Participants responded
      with left and right key presses in two different contexts. They selected the
      responses according to the vertical (context A) or horizontal (context B)
      position of a target. Responses were followed by short/fast movements of the
      target in context A and comparatively long/slow movements in context B.
      Consequently, each response produced short and long effects equally often in both
      contexts. Nevertheless, RTs decreased in contexts with short effects and
      increased in contexts with long effects. Data confirm that action-effect
      associations were acquired context-specifically and that the same actions were
      accessed by different effect anticipations.

PMID- 14595561
TI  - Biphenyl synthase from yeast-extract-treated cell cultures of Sorbus aucuparia.
AB  - Biphenyls and dibenzofurans are the phytoalexins of the Maloideae, a subfamily of
      the economically important Rosaceae. The biphenyl aucuparin accumulated in Sorbus
      aucuparia L. cell cultures in response to yeast extract treatment. Incubation of
      cell-free extracts from challenged cell cultures with benzoyl-CoA and malonyl-CoA
      led to the formation of 3,5-dihydroxybiphenyl. This reaction was catalysed by a
      novel polyketide synthase, which will be named biphenyl synthase. The most
      efficient starter substrate for the enzyme was benzoyl-CoA. Relatively high
      activity was also observed with 2-hydroxybenzoyl-CoA but, instead of the
      corresponding biphenyl, the derailment product 2-hydroxybenzoyltriacetic acid
      lactone was formed.

PMID- 14595562
TI  - Different skeletal muscle HSP70 responses to high-intensity strength training and
      low-intensity endurance training.
AB  - Heat shock protein, e.g. HSP70, can be induced in human skeletal muscle
      undergoing exercise training, and plays important role in adaptation to stress.
      This study was designed to investigate the effects of high-intensity strength
      training and low-intensity endurance training on the HSP70 response to exercise,
      bearing in mind whether HSP70 is induced in the well-trained muscle during low
      intensity endurance training. Six well-trained rowers (male, aged 18 years)
      underwent a training program which consisted of 3 weeks high-intensity training
      (HIT) and 3 weeks low-intensity endurance training (ET), followed by 1 week of
      recovery each (R1 and R2, respectively). HSP70 (2.5 microg total protein loaded)
      was determined by Western blot with reference to a series of known amount of
      standard HSP70. HSP70 mRNA was analyzed by RT-PCR, and the relative percentage
      change was referred to the baseline level (before training). HSP70 increased
      significantly at the end of HIT (from 51 to 73 ng), decreased at the end of R1(66
      ng), and remained unchanged throughout ET and R2. HSP70 mRNA increased
      significantly after HIT (257%) and decreased gradually afterwards (194%, 166%,
      and 119% for R1, ET, and R2, respectively). It can be concluded that: (1) HSP70
      was induced by high-intensity training, but not by endurance training at low
      intensity, and (2) there was a discrepancy in terms of HSP70 regulation between
      the protein and mRNA levels, suggesting that posttranscriptional regulation may
      play a role in HSP70 expression in human skeletal muscle in response to exercise.

PMID- 14595563
TI  - Regulation of arterial blood pressure in humans during isometric muscle
      contraction and lower body negative pressure.
AB  - Previous studies have shown that the blood pressure response to isometric
      handgrip remains unchanged during reductions in preload induced by lower body
      negative pressure (LBNP). The purpose of the present study was to assess the beat
      by-beat haemodynamic mechanisms allowing for precise control of mean arterial
      pressure (MAP). We have followed the cardiovascular variables involved in the
      regulation of MAP during isometric handgrip with and without additional
      application of LBNP during defined periods of the ongoing contraction. Sixteen
      subjects participated. Mean arterial blood pressure (MAP), heart rate (HR),
      stroke volume (SV), cardiac output (CO), blood flow velocity in the brachial
      artery, acral skin blood flow, as well as total (TPR) and local (LPR) peripheral
      resistance were continuously recorded/calculated before, during and after 2 min
      of handgrip both with and without concomitant LBNP. The main finding was that MAP
      increased at the same rate and to the same absolute level whether or not LBNP was
      applied. A uniform increase in MAP was observed even though the cardiovascular
      variables evolved differently in the periods with and without LBNP. At the onset
      of LBNP at -20 mmHg, there was a transient drop in MAP and a transient increase
      in HR, but within seconds, MAP was regulated back to the slope caused by the
      isometric handgrip proper. CO and SV, which were declining gradually, showed an
      additional marked but gradual reduction upon LBNP application. At the same time,
      both LPR and TPR increased markedly and continuously. In summary, the increase in
      MAP during isometric handgrip remained essentially unchanged by LBNP-induced
      alterations in preload. The increase in MAP was caused by a marked increase in
      peripheral resistance. This supports the concept of a central set point,
      continuously regulated upwards as long as the isometric handgrip persists.
      Furthermore, it reveals a considerable flexibility in the cardiovascular control
      mechanisms used to achieve the desired arterial pressure.

PMID- 14595564
TI  - The serum angiotensin-converting enzyme and angiotensin II response to altered
      posture and acute exercise, and the influence of ACE genotype.
AB  - The deletion (D) rather than insertion (I) allele of the angiotensin-converting
      enzyme (ACE) gene is associated with greater ACE activity. We examined: (1) the
      influence of posture change (recumbent to seated) and acute exercise on serum ACE
      and angiotensin II (Ang II) activity; (2) the relationship between ACE and Ang II
      levels; and (3) the influence of ACE genotype on changes in ACE and Ang II levels
      with posture and exercise. Recreationally active young male Caucasians (10 each
      of II, ID and DD genotypes) rested for 35 min supine then 15 min upright, took 20
      min bicycle ergometric exercise at 70% maximum oxygen uptake, then rested for 40
      min. Samples were taken throughout for ACE activity and Ang II levels. Supine ACE
      levels were dependent upon ACE genotype [24.8 (5.7), 26.9 (4.5), 45.5 (6.4) nmol
      His-Leu ml(-1) min(-1); II, ID, DD, respectively; P<0.00005] and thereafter. ACE
      activity rose with assumption of a seated posture [from 32.4 (10.9) nmol His-Leu
      ml(-1) min(-1) to 35.0 (11.5) nmol His-Leu ml(-1) min(-1), P<0.00001], the
      absolute rise being independent of genotype [3.22 (1.92), 1.6 (1.6), 2.4 (2.3)
      nmol His-Leu ml(-1) min(-1); II, ID, DD; P=0.22], unlike percentage change [12.8
      (6.8), 5.6 (5.5), 5.3 (5.0)%; II, ID, DD; P<0.01, and P=0.004 for II vs presence
      of the D allele]. A further genotype-independent rise occurred with exercise
      [+2.9 (3.7) units, P<0.0003]. An associated rise in Ang II levels [30.3 (15.9),
      or 2587.9 (489.76)%, P<0.00001] was independent of ACE genotype or activity.
      Upright posture increases ACE activity, and this may be influenced by ACE
      genotype. ACE activity and Ang II levels rise independently with exercise in a
      non-genotype-dependent fashion.

PMID- 14595565
TI  - Transscleral resection of a ciliary body leiomyoma in a child: case report and
      review of the literature.
AB  - PURPOSE: To present the case of a patient with leiomyoma of the ciliary body and
      discuss the histological features and treatment of this rare intraocular tumor.
      METHODS/CASE REPORT: A 13-year-old boy presented with an asymptomatic tumor of
      the right eye. Visual acuity was 20/20 in both eyes. Ophthalmoscopy revealed an
      amelanotic, vascularized ciliary body tumor with exudative retinal detachment and
      partial transillumination. On ultrasound examination the tumor height was 8 mm
      and a low internal reflectivity was found. T2-weighted MRI scans showed a
      hypointense and T1-weighted scans a hyperintense intraocular mass with
      significant Gd-TPA enhancement. On the assumption that the diagnosis was
      consistent with an amelanotic ciliary body melanoma, a transscleral resection
      with adjuvant ruthenium-106 brachytherapy was performed. Visual acuity was 20/40
      at 6 months after the operation. RESULTS: Routine stains revealed a pleomorphic
      tumor composed mainly of spindle cells with palisading in some areas and a
      prominent intercellular fibrillary background. Immunohistochemistry showed
      positivity for desmin, vimentin and actin. No reactivity with S-100 and HMB-45
      was seen. Intracytoplasmatic filaments and micropinocytotic vesicles were
      detected by transmission electron microscopy. These findings were consistent with
      the diagnosis of a ciliary body leiomyoma. CONCLUSION: Typical clinical features
      of leiomyoma include a dome-shaped configuration and translucency, but the final
      diagnosis can only be confirmed by histology with the aid of immunohistochemistry
      and electron microscopy. Though rare, leiomyoma should be considered in the
      differential diagnosis of amelanotic uveal tumors. Transscleral resection is the
      treatment of choice of anterior uveal leiomyomas, with a fairly good visual
      prognosis.

PMID- 14595566
TI  - Influence of perceived functional and employment status on cardiopulmonary
      resuscitation directives.
AB  - BACKGROUND: Perceptions about functional and employment status before admission
      to the intensive care unit (ICU) may influence how patients and clinicians make
      decisions about cardiopulmonary resuscitation. OBJECTIVE: To examine the
      relationship between cardiopulmonary resuscitation directives established within
      24 hours of admission to the ICU and clinical perceptions of premorbid functional
      and employment status. DESIGN: Prospective observational study in 15 university
      affiliated centers in Canada, the United States, Australia, and Sweden. PATIENTS:
      A total of 1,008 ICU patients aged 18 years or older expected to stay in the ICU
      at least 72 hours. MEASUREMENTS: By using multinomial logistic regression, we
      examined the relationship between functional status and employment status
      perceived by the ICU team 1 month before ICU admission (the independent
      variables) and resuscitation status (the dependent variable). Each patient had
      either an explicit resuscitation directive (to resuscitate or not to
      resuscitate), or an implicit resuscitation directive to resuscitate. RESULTS: On
      average, patients were 61.7 years (+/-17.4 y) old with an Acute Physiology and
      Chronic Health Evaluation (APACHE) II score of 21.5 (+/-8.7); 846 (83.9%) were
      ventilated mechanically within 48 hours and 345 (34.2%) died in the ICU. Most
      patients (793, 78.7%) had no explicit resuscitation directive; 98 (9.7%) had an
      explicit plan to resuscitate, whereas 117 (11.6%) had an explicit plan of do-not
      resuscitate. Of 1,008 patients, 98 (9.7%) were severely functionally limited, 217
      (21.5%) were somewhat limited, 628 (62.3%) were totally independent, and 65
      (6.4%) had unknown functional status 1 month before ICU admission. Severe
      functional status impairment was associated moderately with an explicit plan to
      resuscitate (odds ratio, 2.2 relative to no explicit directive) and associated
      strongly with an explicit do-not-resuscitate plan (odds ratio, 6.2 relative to no
      explicit directive, P value on the difference =.011). This relationship was not
      influenced by age, sex, APACHE II score, medical or surgical status, admission
      diagnosis, employment status, or city. However, severe functional status was
      associated strongly and significantly with an explicit do-not-resuscitate
      directive among those who could not participate in decision making (odds ratio,
      8.2; 95% confidence interval, 4.5-15.0), and more weakly associated in those who
      could participate (odds ratio, 1.7; 95% confidence interval, 0.3-8.6). Being
      unemployed was associated with an increased odds of an explicit resuscitation
      directive versus no explicit directive (odds ratio, 5.5; 95% confidence interval,
      2.2-13.4). CONCLUSIONS: Functional status impairment perceived by the ICU team is
      associated clearly with do-not-resuscitate directives in patients unable to
      participate in decision making. However, the association appears much weaker in
      patients able to participate in decision making. PATIENTS' perceived employment
      status also may influence resuscitation decisions. Our results emphasize the
      challenges of ensuring that crucial resuscitation decisions are not affected
      adversely by patients' inability to participate in decisions, and by their
      functional and employment status.

PMID- 14595567
TI  - Developing and pilot testing quality indicators in the intensive care unit.
AB  - PURPOSE: To develop and implement a set of valid and reliable yet practical
      measures of intensive care units (ICU) quality of care in a cohort of ICUs and to
      estimate, based on current performance, the potential opportunity to improve
      quality. METHODS: We included 13 adult medical and surgical ICUs in urban
      community teaching and community hospitals. To monitor performance on previously
      identified quality measures, we developed 3 data collection tools: the Team
      Leader, Daily Rounding, and Infection Control forms. These tools were pilot
      tested, validated, and modified before implementation. We used published
      estimates of efficacy to estimate the clinical and economic effect of our current
      performance for each of the process measures: appropriate sedation, prevention of
      ventilator-associated pneumonia, appropriate peptic ulcer disease (PUD)
      prophylaxis, appropriate deep venous thrombosis (DVT) prophylaxis, and
      appropriate use of blood transfusions. RESULTS: Performance varied widely among
      the 13 ICUs and within ICUs. The median percentage of days in which ventilated
      patients received therapies that ought to was 64% for appropriate sedation, 67%
      for elevating head of bed, 89% for PUD prophylaxis, and 87% for DVT prophylaxis.
      The median rate of appropriate transfusion was 33%. The failure to use these
      therapies may lead to excess morbidity, mortality, and ICU length of stay.
      CONCLUSION: To improve quality of care, we must measure our performance. This
      pilot study suggests that it is feasible to implement a broad set of ICU quality
      measures in a cohort of hospitals. By improving performance on these measures, we
      may realize reduced mortality, morbidity, and ICU length of stay.

PMID- 14595568
TI  - Heart rate variability as early marker of multiple organ dysfunction syndrome in
      septic patients.
AB  - PURPOSE: To determine whether measuring heart rate variability (HRV) in a group
      of septic patients without multiple organ dysfunction syndrome (MODS) made it
      possible to predict which of them would later develop this syndrome. MATERIAL AND
      METHODS: We studied 46 septic patients without MODS at the time of admission to
      an intensive care unit (ICU). During the first 24 hours of admission, a 10-minute
      electrocardiogram (ECG) was performed and 8 HRV indexes were calculated off-line.
      Eleven patients later developed MODS (MODS group) during their ICU stay, and 28
      did not (non-MODS group). Seven patients were excluded. RESULTS: Although Acute
      Physiological and Chronic Health Evaluation (APACHE II) scores were similar for
      both groups, most HRV indices on admission were reduced significantly in the MODS
      group. Compared with a subset from the non-MODS group (control group, n = 11)
      paired by age, the MODS group had significantly lower low-frequency spectral
      components (LF, P =.0128) and mean squared successive differences of R-R
      intervals (rMSSD) (P =.0473) values. Multivariable logistic regression identified
      LF as the best predictor of MODS and received operating characteristic (ROC)
      curves established its cut-off point at 18 ms(2). Mortality rates were 63.6% for
      the MODS group and 0% for the non-MODS group (P <.0001). CONCLUSIONS: Reduction
      of HRV on ICU admission may be useful in identifying septic patients at risk for
      development of MODS.

PMID- 14595569
TI  - Increased risk associated with pulmonary artery catheterization in the medical
      intensive care unit.
AB  - PURPOSE: To determine whether the frequency of use of a pulmonary artery catheter
      (PAC) was declining over a 5-year period in a medical intensive care unit (ICU),
      and to assess whether mortality was higher in patients in whom a PAC was used on
      the day of ICU admission compared with matched controls. METHODS: Observational,
      retrospective, matched-set study using prospectively collected Acute Pysiology,
      Age and Chronic Health Evaluation (APACHE) III data during a 5-year period, from
      1995 to 2000, at a 15-bed medical ICU in an academic referral center. A total of
      360 patients, 202 men and 158 women, in whom a PAC was placed on the first ICU
      day, were compared with 690 controls without a PAC, matched by primary diagnosis
      group and APACHE III-predicted hospital mortality. RESULTS: A PAC was used during
      the first day in 7.7% of ICU admissions (yearly range, 5.7% to 9.1%) and did not
      change significantly during the study period. A total of 187 study patients
      (27.0%) without a PAC and 132 (36.7%) with a PAC died during their hospital stay.
      PAC use was a significant risk factor for hospital death from a univariate
      analysis (odds ratio = 1.5; 95% confidence interval (CI), 1.1-2.1; P =.006). From
      multivariate analysis, the use of a pulmonary artery catheter was a significant
      risk factor for hospital death after adjusting for age, date of ICU admission,
      and predicted hospital mortality (odds ratio = 1.5; 95% CI; 1.1-2.0; P =.016).
      CONCLUSION: PAC use on the day of admission to a medical ICU was associated with
      an increased risk for hospital death.

PMID- 14595570
TI  - Pandemic influenza-implications for critical care resources in Australia and New
      Zealand.
AB  - OBJECTIVES: To quantify resource requirements (additional beds and ventilator
      capacity), for critical care services in the event of pandemic influenza.
      MATERIALS AND METHODS: Cross-sectional survey about existing and potential
      critical care resources. Participants comprised 156 of the 176 Australasian
      (Australia and New Zealand) critical care units on the database of the Australian
      and New Zealand Intensive Care Society (ANZICS) Research Centre for Critical Care
      Resources. The Meltzer, Cox and Fukuda model was adapted to map a range of
      influenza attack rate estimates for hospitalisation and episodes likely to
      require intensive care and to predict critical care admission rates and bed day
      requirements. Estimations of ventilation rates were based on those for community
      acquired pneumonia. RESULTS: The estimated extra number of persons requiring
      hospitalisation ranged from 8,455 (10% attack rate) to 150,087 (45% attack rate).
      The estimated number of additional admissions to critical care units ranged from
      423 (5% admission rate, 10% attack rate) to 37,522 (25% admission rate, 45%
      attack rate). The potential number of required intensive care bed days ranged
      from 846 bed days (2 day length of stay, 10% attack rate) to 375,220 bed days (10
      day length of stay, 45% attack rate). The number of persons likely to require
      mechanical ventilation ranged from 106 (25% of projected critical care
      admissions, 10% attack rate) to 28,142 (75% of projected critical care
      admissions, 45% attack rate). An additional 1,195 emergency ventilator beds were
      identified in public sector and 248 in private sector hospitals. Cancellation of
      elective surgery could release a potential 76,402 intensive care bed days (per
      annum), but in the event of pandemic influenza, 31,150 bed days could be required
      over an 8- to 12-week period. CONCLUSION: Australasian critical care services
      would be overwhelmed in the event of pandemic influenza. More work is required in
      relation to modelling, contingency plans, and resource allocation.

PMID- 14595571
TI  - Cost-effectiveness of recombinant human activated protein C and the influence of
      severity of illness in the treatment of patients with severe sepsis.
AB  - PURPOSE: To evaluate the cost-effectiveness of recombinant human activated
      protein C (rhAPC) compared with usual therapy for patients with severe sepsis,
      and also to determine the influence that severity of illness exerts on cost
      effectiveness. MATERIALS AND METHODS: We use a Markov model-based cost
      effectiveness analysis of treatment strategies for patients with severe sepsis.
      Therapy includes treatment with either rhAPC and usual therapy, or usual therapy
      alone. Probabilities for clinical outcomes were obtained from a large randomized
      clinical trial comparing the use of rhAPC with placebo (PROWESS study) and from
      outcomes literature for patients with severe sepsis and its complications. Cost
      estimates were based on Medicare reimbursement rates, Health Care Financing
      Administration information and the literature. Outcome measures include life
      years, quality-adjusted life-years (QALYs), costs, and incremental cost
      effectiveness. RESULTS: Compared with usual therapy alone, rhAPC treatment for
      patients with very severe sepsis (APACHE II score > or = 25) was associated with
      an incremental cost-effectiveness ratio of $13 493/QALY. Treatment of patients
      with less severe sepsis with rhAPC (APACHE II score < 25) had an incremental cost
      effectiveness ratio of $403,000/QALY. For patients with very severe sepsis the
      incremental cost-effectiveness ratio for treatment with rhAPC remained under
      $30,000/QALY, over a broad range of variables, including costs of rhAPC, costs of
      acute care and costs and probabilities of complications of treatment. For
      patients with less severe sepsis, drug costs would need to fall well below
      current market price before achieving cost-effectiveness. A probabilistic
      sensitivity analysis comparing rhAPC treatment with usual therapy for patients
      with very severe sepsis showed that < 1% of Monte Carlo simulations had
      incremental cost-effectiveness ratios > $50,000/QALY. CONCLUSIONS: The use of
      rhAPC for the treatment of patients with very severe sepsis, as determined by
      APACHE II score > or = 25, appears cost-effective, while treatment of patients
      with APACHE II score < 25 is not cost-effective.

PMID- 14595572
TI  - A clinical model for Health Services Research-the Medical Emergency Team.
AB  - Health Services Research (HSR) is a relatively recent discipline which describes
      how health care delivery occurs and the evaluation of that care. The
      implementation of a Medical Emergency Team (MET) is an example of a health
      service intervention. The aim of the MET is to extend the expertise of Intensive
      Care across the hospital to all at-risk patients. The MET criteria for calling
      are based on simple abnormalities in vital signs with an extra "worried" category
      to empower junior medical and nursing staff to call for help. The concept is
      based on early intervention and resuscitation of the seriously ill, hopefully
      leading to improved outcomes from intensive care and perhaps even avoiding
      admission to an intensive care unit. The problems of implementing major health
      service change and evaluating the effectiveness of that change presents a
      different challenge to evaluating a new drug or procedure and is approached
      within different research frameworks.

PMID- 14595575
TI  - Plants used in cosmetics.
AB  - This review describes the use of some natural products in cosmetic preparations,
      due to their low mammalian toxicity, with a brief description of the major use,
      plant parts used, the actives responsible for effect and the benefits of such
      products. Their use in skin care; such as dryness, eczema, acne, free-radical
      scavenging, antiinflammatory, antiaging and skin protection effects are
      explained, and also the use in hair care as hair growth stimulants, hair
      colorants, and for hair and scalp complaints such as dandruff. Essential oils
      when incorporated into finished products impart many benefits such as a pleasant
      aroma in perfumery, shine or conditioning effects in hair care products,
      emolliency and improving the elasticity of the skin.

PMID- 14595576
TI  - Antitumor activity of total alkaloid fraction of solanum pseudocapsicum leaves.
AB  - The total alkaloid fraction of the methanolic extract of Solanum pseudocapsicum
      leaves was tested for its in-vivo antitumor activity against Dalton's Lymphoma
      Ascites model in mice. The total alkaloid fraction at 2.5 and 5.0 mg/kg body
      weight doses exhibited antitumor activity as revealed by the significant increase
      in the mean survival time and the percentage increase in life span of tumor
      bearing mice. The antitumor activity observed may be due to its cytotoxic
      properties. However the treatment caused a significant decrease in the body
      weight below the normal indicating the toxicity of the treatment.

PMID- 14595578
TI  - Effect of 14-deoxyandrographolide on calcium-mediated rat uterine smooth muscle
      contractility.
AB  - In this study, the effect of 14-deoxyandrographolide (14-DAP) on calcium channel
      dependent rat uterine smooth muscle contraction was evaluated. Using a tissue
      bath preparation, 14-DAP was able to reduce the contractile response to 0.3 and
      3.0 mm of CaCl(2), with an IC(50) of 1.24 +/- 0.23 x 10(-5) m and 5.94 +/- 0.29 x
      10(-5) m, respectively. 14-DAP shifted the CaCl(2) cumulative dose response curve
      to the right, increasing the EC(50) from 2.08 +/- 0.20 x 10(-4) m to 4.22 +/-
      0.22 x 10(-4) m (5 micrometer 14-DAP) and 2.5 +/- 1.0 x 10(-3) m (50 micrometer
      14-DAP). In order to determine if 14-DAP had any effect on intracellular calcium,
      the relaxant response to 14-DAP following contraction by oxytocin, PGF(2alpha)
      and vanadate in Ca(+2)-free solution was compared with that of isoproterenol and
      phenylbutazone. While isoproterenol and phenylbutazone relaxed the smooth muscle
      in a dose-dependent manner, 14-DAP did not have any effect on either the
      oxytocin, PGF(2alpha) or vanadate-induced smooth muscle contraction. Based on
      these data, it appears that 14-DAP is an uterine smooth muscle relaxant which
      produces a selective blockade of voltage operated calcium channels.

PMID- 14595577
TI  - Antimicrobial activity of essential oil and methanol extracts of Achillea
      sintenisii Hub. Mor. (Asteraceae).
AB  - The essential oil, obtained by Clevenger distillation, and water-soluble and
      water-insoluble parts of the methanol extracts of Achillea sintenisii Hub. Mor.
      were individually assayed for their antimicrobial activities against 12 bacteria
      and two yeasts, Candida albicans and C. krusei. No activity was exhibited by the
      water-soluble subfraction, whereas both the water-insoluble subfraction of the
      methanol extracts and the essential oil were found to be active against some test
      microorganisms studied. Since the essential oil possessed stronger activity than
      the other extracts tested, it was further fractionated and the fractions were
      evaluated for their antimicrobial activity, followed by GC-MS analysis, resulting
      in the identification of 32 compounds which constituted 90.2% of the total oil.
      The GC-MS analysis of the oil and its fractions revealed that the main components
      of the oil, e.g. camphor and eucalyptol, possessed appreciable activity against
      C. albicans and Clostridium perfringens. The fi ndings presented here also
      suggest that the other constituents of the oil, e.g. borneol and piperitone can
      also be taken into account for the activity observed.

PMID- 14595579
TI  - Protective effect of Astragali radix extract on interleukin 1beta-induced in fl
      ammation in human amnion.
AB  - The aim of this study was to investigate the effect of Astragali radix extract on
      interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha production and
      prostaglandin E(2) (PGE(2)) and leukotriene C(4) (LTC(4)) release from IL-1beta
      stimulated human amnion. Primary monolayer cultures of amnion cells were
      established from women undergoing elective caesarean section before the onset of
      labour. Production of both IL-6 and TNF-alpha was stimulated in a concentration
      dependent manner by proinflammatory cytokine IL-1beta (0.01-10 ng/mL). Astragalus
      extract inhibited IL-6 production by approximately 75% from cells under IL-1beta
      stimulated conditions. Treatment of amnion cells with IL-1beta (0.01-10 ng/mL)
      resulted in a significant increase in PGE(2) release. Incubation of the cells
      with the extract for 24 h significantly inhibited IL-1beta-induced PGE(2)
      production. A concentration-dependent increase in LTC(4) production by amnion
      cells occurred in response to IL-1beta. Astragalus extract blocked the effect of
      IL-1beta in LTC(4) production in human amnion. These results indicate that
      Astragali radix has a broad antiinflammatory effect in human amnion and may be
      considered a promising agent to protect preterm labour.

PMID- 14595580
TI  - Pharmacokinetic and pharmacological interactions between ticlopidine
      hydrochloride and Kangen-Karyu - Chinese traditional herbal medicine.
AB  - Kangen-Karyu (KGK), containing peony root, cnidium rhizome, saf flower, cyperus
      rhizome, saussurea root and Salvia miltiorrhiza root, is a Chinese traditional
      medicine formula to invigorate the 'blood' and dispel 'blood stasis', arising
      from poor blood circulation. The present study evaluated the pharmacokinetic and
      pharmacological interactions between KGK and ticlopidine hydrochloride.
      Ticlopidine was administered orally or intravenously to KGK-treated rats, and its
      plasma concentrations were measured. KGK did not significantly affect the
      pharmacokinetic parameters of ticlopidine in rats treated with both oral and
      intravenous administration. Ticlopidine alone significantly prolonged the mouse
      tail-bleeding time and adenosine 5'-diphosphate-induced ex vivo platelet
      aggregation, which was slightly augmented by KGK. It is suggested that the
      combined therapy of ticlopidine and KGK may augment the antithrombotic effects,
      and that the dosage of ticlopidine should be reduced to prevent thrombotic
      thrombocytopenic purpura, a severe adverse effect of ticlopidine.

PMID- 14595581
TI  - Seungnoidan increases cerebrocortical ATP and acetylcholine contents in
      ovariectomized rats.
AB  - This study investigated the effects of Seungnoidan (SND), which has been widely
      used as a remedy for cerebroneuronal diseases in Korean folk medicine, on the
      cerebrocortical adenosine triphosphate (ATP) and acetylcholine (ACh) contents in
      ovariectomized (OVX) rats. Female Sprague-Dawley rats were ovariectomized and
      maintained for 12 weeks to deplete ovarian steroid hormones, followed by oral
      administration of SND at 500 mg/kg/day for 14 weeks. SND markedly attenuated the
      high rate of body weight increase in OVX rats, and also reduced the decline of
      cerebral weight caused by ovariectomy (p < 0.05). Superfusion of SND at 50 mg/kg
      significantly increased the rate of cerebral blood fl ow, but did not change the
      mean arterial blood pressure. Deprivation of ovarian steroid hormones
      significantly decreased the cerebral ATP, choline and ACh contents, and these
      reductions were reduced by treatment of OVX rats with SND (p < 0.01).
      Additionally, SND also significantly elevated the cerebral choline
      acetyltransferase activities reduced by OVX (p < 0.01). Taken together, these
      results suggest that the pharmacological properties of SND may be implicated in
      the improvement of metabolic pathways of cerebral energy and cholinergic
      neurotransmitter function induced by deprivation of ovarian steroid hormones, and
      SND may be a promising herbal remedy for treatment of cerebral dysfunctions
      including dementia.

PMID- 14595582
TI  - Antinociceptive activity of Sempervivum tectorum L. extract in rats.
AB  - The extract of Sempervivum tectorum L. (Crassulaceae) containing several
      flavonoids is widely used as an antiinflammatory agent in folk medicine. Previous
      studies have demonstrated that various flavonoids or flavonoid-containing plant
      extracts produce significant antinociception, but no data are available
      concerning their antinociceptive effect especially at the spinal level. The
      purpose of the present study was to investigate the antinociceptive activity of
      Sempervivum tectorum L. extract on acute and inflammatory pain sensitivity in
      awake rats. The pain sensitivity was assessed by the acute tail- flick test in
      intact rats and by the paw withdrawal test after carrageenan-induced inflammation
      using heat stimulus. The plant extract was administered intraperitoneally and
      intrathecally in rats. The intraperitoneal injection of a high dose of the
      extract (1000 mg/kg) significantly (p < 0.05) increased the paw withdrawal
      latency of the inflamed paw. The intrathecal administration (30-300 micro g)
      caused a small, but significant increase (10%-15%) in tail- flick latency. In the
      carrageenan-induced inflammatory model, the intrathecally applied extract (30
      1000 micro g) significantly decreased, but did not relieve the thermal
      hyperalgesia. The results suggest that the spinal cord does not seem to play an
      important role in the antinociceptive effects of this plant extract.

PMID- 14595583
TI  - Composition and antimicrobial activity of Achillea clavennae L. essential oil.
AB  - The volatile constituents of Achillea clavennae L. (Asteraceae), rare plant of
      Europe, have been analysed using GC/MS. Twenty- five components making up 81.6%
      of the oil were characterized with camphor (29.5%), myrcene (5.5%), 1,8-cineole
      (5.3%), beta-caryophyllene (5.1%) and linalool (4.9%) being the major
      constituents. The essential oil was evaluated for antibacterial and antifungal
      activities. The screening of the antimicrobial activity of essential oil was
      conducted by a disc diffusion test against Gram-positive (Bacillus subtilis,
      Bacillus cereus, Staphylococcus aureus, Streptococcus faecalis), Gram-negative
      (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus
      mirabilis) and fungal organisms (Aspergillus niger, Aspergillus fumigatus,
      Candida albicans). The activity was more pronounced against Gram-negative and
      fungal organisms than against Gram-positive bacteria. A. clavennae oil was found
      to possess antimicrobial activity against Klebsiella pneumoniae, Pseudomonas
      aeruginosa and all fungal organisms.

PMID- 14595584
TI  - Antioxidant activity of extracts from Alpinia katsumadai seed.
AB  - Alpinia katsumadai (Zingiberaceae) has been widely used in traditional Chinese
      medicine to treat a variety of conditions such as emesis and gastric disorders.
      However, very little is known about the cellular actions by which this plant
      mediates its therapeutic effects. Various aspects of antioxidant activity were
      evaluated in a total extract derived from Alpinia katsumadai seed in this study.
      Relatively high levels of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging
      activity were detected in the total extract (IC(50) 1.6 microgram/mL). Other
      known compounds such as (-)-epigallocatechine-3-gallate (EGCG) and resveratrol
      showed IC(50) values of <0.8 and 4.8 microgram/mL, respectively. The total
      extract also enhanced the viability of Chinese hamster lung fibroblast (V79-4)
      cells and inhibited H(2)O(2)-induced apoptosis. The total extract of Alpinia
      katsumadai also dose-dependently enhanced the activities of superoxide dismutase
      (SOD), catalase (CAT) and glutathione peroxidase (GPX) in V79-4 cells, and these
      effects were comparable to other antioxidant compounds such as EGCG and
      resveratrol. Taken together, our findings show that Alpinia katsumadai contains
      significant antioxidant activity.

PMID- 14595585
TI  - In vivo and in vitro studies on the anticancer activity of Copaifera multijuga
      hayne and its fractions.
AB  - Copaiba oil resin (COR) obtained from Copaifera multijuga Hayne has been used in
      popular medicine as an antinflammatory and for the treatment of bronchitis,
      ulcers and cancer. The aim of this study was to evaluate the action of COR and
      its fractions on the inhibition of lung metastasis and tumour growth induced by
      B16F10 melanoma cells in mice and cytotoxicity in vitro using Trypan Blue
      exclusion method and MTT conversion. Mice which have received subcutaneously
      B16F10 cells developed a solid tumour that reached a peak at 17 days. Together
      with the increase in tumour growth we also observed an increase in the number of
      lung nodules. There was a positive correlation between the in vitro cytotoxic
      assay and in vivo antitumour activity. The oral administration of COR (at 2 g/Kg
      in the days 3, 5, 7, 10, 12 and 14 after inoculation of tumoral cells) reduced
      tumour growth by 58% and tumour weight by 76%. At the same dose COR reduced the
      number of lung nodules by 47.1%. In vitro experiments showed that COR incubated
      with the melanoma cell line reduced cell viability in a concentration and time
      dependent manner. Diterpenic and sesquiterpenic fractions or reconstituted oil
      induced cytotoxicity. Our results shows that COR and its fractions have
      tumouricidal activity in the melanoma cell line in both models in vivo and in
      vitro.

PMID- 14595587
TI  - Evaluation of in vitro antiviral activity in methanol extracts against in fl
      uenza virus type A from Korean medicinal plants.
AB  - Methanol extracts from 101 Korean medicinal plants were tested for inhibitory
      activity against influenza virus type A by means of a modified haemagglutination
      inhibition (HI) test. MM-57, MM-72, MM-104 and MM-110, four of 101 extracts
      tested exhibited strong anti-influenza virus type A activity at concentration
      ranges of 0.78-6.25 mg/mL, 0.78-3.13 mg/mL, 0.78-1.56 mg/mL and 0.0975-0.39
      mg/mL, respectively. The extracts MM-57, MM-72 and MM-110 showed very strong anti
      influenza virus type A activity in the range 1.56-6.25 mg/mL, 1.56-3.13 mg/mL and
      195-390 micro g/mL, respectively. The four methanol extracts were weakly
      cytotoxic to red blood cells. These results demonstrated that four methanol
      extracts of Korean medicinal plants exhibit strong anti-influenza virus type A
      activity, and weak cytotoxic effects. They may inhibit attachment of the virus to
      the cell and may therefore be used for prophylaxis.

PMID- 14595586
TI  - The effect of a catechin-rich extract of Cocos nucifera on lymphocytes
      proliferation.
AB  - Catechins are polyphenols with antioxidant activity. The fruit Cocos nucifera
      (Palmae) has a fi ber husk rich in catechins and the local population of
      northeast Brazil uses it as a medicine against various diseases. An anti
      bacterial and anti-viral activity has been already observed using this substance.
      Plant extracts, from other sources, rich in catechins are inhibitory to tumour
      cells, suppressing their proliferation. The aim of the present work was to verify
      if catechins isolated from Cocos nucifera were capable of inhibiting cell
      proliferation. An extract obtained from Cocos nucifera was purified through
      adsorption chromatography using the resin XAD-2. The purified material was used
      in cultures of an erythroleukaemia cell line (K562) and on normal human
      peripheral blood lymphocytes. Cell viability was assessed using MTT. Cellular
      proliferation was measured by [(3)H]-thymidine incorporation and cell cycle
      analysis in a fl ow cytometer. A dose-dependent inhibitory effect was observed on
      tumour cells and on lymphocytes activated by phytohemaglutinin (PHA) or phorbol
      ester. For PHA this effect was irreversible being already established on the fi
      rst four hours of culture.

PMID- 14595588
TI  - Antioxidant principles from the needles of red pine, Pinus densi fl ora.
AB  - Antioxidant activity of Pinus densiflora Sieb. et Zucc. (Pinaceae) was evaluated
      for potential to inhibit hydroxyl radicals, inhibit total reactive oxygen species
      generation in kidney homogenates using 2',7'-dichlorodihydro fluorescein
      diacetate (DCHF-DA) and scavenge authentic peroxynitrites. The methanolic extract
      of P. densiflora showed strong antioxidant activity in the tested model systems
      and thus fractionated with several solvents. The antioxidant activity potential
      of the individual fraction was in the order of ethyl acetate > n-butanol > water
      > dichloromethane fraction. The ethyl acetate soluble fraction exhibiting strong
      antioxidant activity was further puri fi ed by repeated silica gel and Sephadex
      LH-20 column chromatographies. An active lignan (+)-isolarisiresinol
      xylopyranoside, as well as two active flavonoids [kaempferol 3-O-beta
      galactopyranoside and its 6"-acetyl derivative], were isolated.

PMID- 14595589
TI  - Toxicity and antiviral activity of cinnabarin obtained from Pycnoporus sanguineus
      (Fr.) Murr.
AB  - This work describes the cytopathic effect on cells, cytotoxic action on mice, and
      antiviral activity of cinnabarin. This substance had no effect on mouse
      neuroblastoma cells (NA cell, ATCC clone C-1300) at a concentration of 0.31
      mg/ml, it was not able to cause toxic effects in mice at concentrations of 1000
      mg/kg, and reduced by four times the titers of the rabies virus at concentrations
      of 0.31 mg/ml.

PMID- 14595590
TI  - Virucidal activity of essential oils from aromatic plants of San Luis, Argentina.
AB  - Essential oils obtained from eight aromatic plants of San Luis Province,
      Argentina, were screened for virucidal activity against herpes simplex virus type
      1 (HSV-1), Junin virus (JUNV) and dengue virus type 2 (DEN-2). The most potent
      inhibition was observed with the essential oil of Lippia junelliana and Lippia
      turbinata against JUNV with virucidal concentration 50% (VC(50)) values in the
      range 14-20 ppm, whereas Aloysia gratissima, Heterotheca latifolia and Tessaria
      absinthioides inhibited JUNV in the range 52-90 ppm. The virucidal activity was
      time- and temperature-dependent. The essential oils of A. gratissima, Artemisia
      douglasiana, Eupatorium patens and T. absinthioides inactivated HSV-1 at 65-125
      ppm. However, only A. douglasiana and E. patens had any discernible effect on DEN
      2 infectivity with VC(50) values of 60 and 150 ppm, respectively.

PMID- 14595591
TI  - In vitro immunopotentiating properties and tumour cell toxicity induced by
      Lophophora williamsii (peyote) cactus methanolic extract.
AB  - Lophophora williamsii, also known as peyote, is found primarily in dry regions
      from Central Mexico, including the Mexican States of Nayarit, San Luis Potosi,
      Zacatecas, Nuevo Leon, Chihuahua, Coahuila and Tamaulipas, to Texas particularly
      in regions along Rio Grande. Peyote extracts have been associated with
      stimulating the central nervous system and regulating blood pressure, sleep,
      hunger and thirst. However, there is no evidence of any effect of peyote on the
      immune system or against tumour cell growth. The present study was designed to
      evaluate the in vitro effects of peyote methanolic extracts on some parameters of
      mouse and human leukocyte immunocompetence and tumour cell growth. Peyote extract
      (0.18-18 micro g/mL) activated nitric oxide production by murine macrophages, and
      stimulated up to 2.4-fold proliferation of murine thymic lymphocytes. In
      addition, peyote extract induced up to 1.85-, 2.29- and 1.89-fold increases in
      mRNA signal of IL-1, IL-6 and IL-8 by human leukocytes. Also examined were the
      effects of peyote extracts on murine lymphoma L5178Y-R and fi broblastoma L929,
      and human myeloid U937 and mammary gland MCF7 tumour cell growth using 3-[4,5
      dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT). Peyote extracts were
      toxic for MCF7, L5178Y-R, U937 and L929 (18 mg/mL peyote extract caused 1.3%, 8%,
      45% and 60% viability respectively) cell lines.

PMID- 14595593
TI  - Fenugreek affects the activity of beta-glucuronidase and mucinase in the colon.
AB  - The effect of fenugreek seeds on the activities of beta-glucuronidase and
      mucinase during 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis in rats
      was studied. Rats were given a weekly subcutaneous injection of DMH at a dose of
      20 mg/kg body weight, for 15 weeks. Fenugreek seed powder was weighed depending
      upon the weight of individual rats and incorporated in the powdered pellet diet
      at a dose of 2 g/kg body weight. After an experimental period of 30 weeks the
      activity of beta-glucuronidase significantly increased in the colon, intestine,
      liver and colon contents in DMH administered rats when compared to an untreated
      control group. Increase in beta-glucuronidase may increase the hydrolysis of
      carcinogen-glucuronide conjugate, liberating carcinogen and/or co-carcinogen
      within the colonic lumen. Inclusion of fenugreek seed powder in the diet
      significantly decreased the activity of beta-glucuronidase in all the tissues
      studied. This may prevent the free carcinogens from acting on colonocytes.
      Mucinase helps in hydrolysing the protective mucin. Mucinase activity was
      increased in the colon content and fecal content of animals given DMH when
      compared to control, while the activity was significantly reduced in animals
      given DMH + fenugreek when compared to animals given DMH only. Our study shows
      that supplementation of fenugreek seeds in the diet inhibits colon
      carcinogenesis, by modulating the activities of beta-glucuronidase and mucinase.
      The beneficial effect may be attributed to the presence of fibre, flavonoids
      and/or saponins.

PMID- 14595592
TI  - Biological activities of Prunella vulgaris extract.
AB  - The organic fraction (OF; 25.7% w/w of rosmarinic acid) of Prunella vulgaris
      (total extract) was found to exhibit the following: scavenging activity on
      diphenylpicrylhydrazyl radical (DPPH), inhibition of in vitro human LDL Cu(II)
      mediated oxidation, protection of rat mitochondria and rat hepatocytes exposed to
      either tert-butyl hydroperoxide, or to Cu(II) and Fe(III) ions. OF also showed a
      potential to inhibit rat erythrocyte haemolysis and it reduced the production of
      LTB(4) in bovine PMNL generated by the 5-lipoxygenase pathway. Other observations
      included antiproliferative effects against HaCaT cells and mouse epidermal
      fibroblasts and a moderate OF antimicrobial activity on gram-positive bacteria.
      Rosmarinic, caffeic and 3-(3,4-dihydroxyphenyl)lactic acids exhibited less potent
      activity than the plant extract in all bioassays. The antioxidative,
      antimicrobial, together with antiviral effects offer good prospects for the
      medicinal applications of P. vulgaris.

PMID- 14595594
TI  - Antiasthmatic property of polyherbal preparation E-721 B.
AB  - E-721B and its aqueous extract were studied for its antiasthmatic effect in
      various experimental models using rats and guinea pigs. E-721B produced
      significant and dose-dependent inhibition of peritoneal mast-cell degranulation
      induced by compound 48/80 and egg-albumin in sensitised rats. The inhibition was
      comparable to that with disodium cromoglycate, ketotifen, and prednisolone. E
      721B administered 2 h before the experiment and once daily for seven days
      significantly increased the preconvulsion time of acetylcholine and histamine
      aerosol-induced bronchospasm. It also significantly reduced mortality in
      guineapigs produced by egg albumin-induced anaphylactic shock and also reduced
      bronchoalveolar fluid eosinophil count in the same animals. E-721B significantly
      inhibited the acetylcholine and histamine-induced contraction of different
      isolated smooth muscle preparations from rats and guinea pigs. Contrary to these
      findings E-721B produced dose-dependent contraction of the rat anococcygeus
      muscle which was blocked by prazosin. Thus our observations establish the
      antiasthmatic potential of this herbal formulation.

PMID- 14595595
TI  - Oral hypoglycaemic activity of Ipomoea aquatica in streptozotocin-induced,
      diabetic wistar rats and Type II diabetics.
AB  - Ipomoea aquatica Forsk is a common green leafy vegetable consumed in many parts
      of the world. The present study was designed to investigate the oral
      hypoglycaemic activity of Ipomea aquatica in streptozotocin induced diabetic
      Wistar rats, and Type II diabetic patients. Experimental diabetes was induced
      with streptozotocin in Wistar rats. The rats were then divided into test and
      control groups. In addition to the standard feed given to both groups the test
      was fed with the shredded leaves of Ipomoea aquatica (3.4 g/kg) for one week.
      Type II diabetic patients were subjected to a glucose challenge before and after
      a single dose of blended I. aquatica. Patients acted as their own controls. The
      results revealed that consumption of the shredded, fresh, edible portion of I.
      aquatica for one week, effectively reduced the fasting blood sugar level of
      streptozotocin-induced diabetic rats (p = 0.01). When subjected to a glucose
      challenge, the Type II diabetic subjects showed a significant reduction (p =
      0.001) in the serum glucose concentration 2 h after the glucose load. However, it
      was not significantly reduced at 1 h (p < 0.09) post glucose load. There was a
      29.4% decrease in the serum glucose concentration of the diabetic patients when
      treated with the plant extract.

PMID- 14595596
TI  - Anti-HIV-1 limonoid: first isolation from Clausena excavata.
AB  - A limonoid, clausenolide-1-ethyl ether (1) and two coumarins, dentatin (2) and
      nor-dentatin (3), were isolated from Clausena excavata. Limonoid 1 was obtained
      from the crude ethanol extract of the rhizomes and the roots but had not
      previously been isolated from C. excavata and exhibited HIV-1 inhibitory
      activity. Coumarins 2 and 3, with their structures related to an anti-HIV-1
      substance, (+)-calanolide A (4), were obtained from the crude chloroform extract
      of the rhizomes. Both induced toxicity to cells used in a syncytium assay for
      anti-HIV-1 activity. These compounds, 1-3, did not show any cytotoxic effect
      against KB and BC-1 cell lines (IC(50) value > 20 microgram/mL).

PMID- 14595597
TI  - Anti fi larial potential of the fruits and leaves extracts of Pongamia pinnata on
      cattle filarial parasite Setaria cervi.
AB  - The effect of aqueous and alcohol extracts of the fruits and leaves of Pongamia
      pinnata (Linn.) Merr. (Syn. Pongamia glabra Vent, leguminosae) on the spontaneous
      movements of both the whole worm and the nerve-muscle preparation of Setaria
      cervi and on the survival of micro fi lariae in vitro was studied. The aqueous
      and alcohol extracts of fruits and the alcohol extract of leaves caused an
      inhibition of spontaneous movements of the whole worm and the nerve-muscle
      preparation of S. cervi. The initial stimulatory effect was not observed with the
      aqueous extract of fruits on the nerve-muscle preparation. The concentration
      required to inhibit the movements of the whole worm preparation was 250 micro
      g/mL for aqueous, 120 micro g/mL for alcohol extract of fruits and 270
      microgram/mL for alcohol extracts of the leaves. The concentrations of P. pinnata
      extracts required to produce an equivalent effect on the nerve-muscle preparation
      were 25 micro g/mL, 5 micro g/mL and 20 micro g/mL, respectively, suggesting a
      cuticular permeability barrier.

PMID- 14595598
TI  - Analgesic properties of some ethiopian medicinal plants in different models of
      nociception in mice.
AB  - Many people use analgesic plants to relieve pain and inflammation though most of
      them have not yet been proved to possess such properties. The objective of the
      present study was to screen the aqueous and ethanol extracts of four Ethiopian
      traditionally used medicinal plants for analgesic properties. Aqueous and ethanol
      extracts of the plant materials were screened for their analgesic properties in
      mice using tail-flick, hot-plate and tail-pinch tests at three dose levels.
      Normal saline and standard analgesics were employed as negative and positive
      controls, respectively. The plants subject for the present screening were Ocimum
      suave, Ocimum lamiifolium, Lippia adoensis, and Ajuga remota. All extracts were
      observed to possess analgesic properties with varying potencies in tail-flick and
      hot-plate tests. Analgesic activity, however was not observed with tail-pinch
      test. The analgesic potencies also varied with concentrations and time after
      administration. From the present findings, it can be concluded that the extracts
      of all the plant materials have got analgesic properties with fast onset of
      action whose mechanisms need to be investigated further.

PMID- 14595599
TI  - Effects of Jaoga-Yukmiwon(R), a Korean herbal medicine, on chondrocyte
      proliferation and longitudinal bone growth in adolescent male rats.
AB  - Externally visible growth of the body is the result of proliferation of
      chondrocytes and longitudinal bone growth. The effects of the Korean herbal
      medicine, Jaoga-Yukmiwon((R)), on the growth of adolescent rats were investigated
      in the present study. The proliferation ratio of chondrocytes was calculated from
      5-bromo-2'-deoxyuridine incorporation during DNA synthesis. The 5-bromo-2'
      deoxyuridine incorporation ratio of the control group was 21.1 +/- 3.5%, and
      Jaoga-Yukmiwon((R)) administration markedly increased the ratio to 34.5 +/- 4.6%
      (p < 0.05). The bone formation rate of longitudinal bone was estimated by
      labelling with tetracycline, which binds to newly formed bone. The bone formation
      rate in the tibia of Jaoga-Yukmiwon((R))-administered rats was increased to 405.1
      +/- 4.3 micro m (p < 0.05) from 292.2 +/- 11.8 micrometer (control value). The
      height of the growth plate in the administrated rats was increased to 614.6 +/-
      10.0 micro m (p < 0.05) from 552.3 +/- 17.1 micro m. The bone morphogenetic
      protein-2 immunostaining in the growth plate was also increased. These results
      suggest that Jaoga-Yukmiwon((R)) may promote longitudinal bone growth during the
      developmental period.

PMID- 14595601
TI  - Protection by hot water extract of Panax notoginseng on chronic ethanol-induced
      hepatotoxicity.
AB  - The purpose of this study was to investigate the antioxidant effects of a hot
      water extract of Panax notoginseng (PNG) against chronic ethanol-induced
      hepatotoxicity. Fifty mice were divided into fi ve equal groups with 10 in each
      group. Group 1 (control) received saline, whereas group 2 received ethanol (70%,
      0.1 mL, p.o.) once daily for 4 weeks, which induced hepatotoxicity, manifested
      biochemically by a significant elevation of serum enzyme activities, such as SGOT
      and SGPT. Hepatotoxicity was further evidenced by a significant increase in the
      hepatic lipid peroxidation measured. Groups 3-5 were administered a hot water
      extract of PNG at doses of 10, 25 and 50 mg/kg 2 weeks after initiating oral
      administration of ethanol, for a further 2 weeks. PNG ameliorated the rise in
      serum sGOT and sGPT induced by chronic ethanol administration. The mice were
      killed after PNG administration. In a separate study, PNG inhibited the lipid
      peroxidation in the mouse liver homogenate induced by ethanol in a dose-dependent
      manner. The findings indicate that PNG is an efficient cytoprotective agent
      against chronic ethanol-induced hepatotoxicity, possibly through inhibition of
      the production of oxygen-free radicals that cause lipid peroxidation.

PMID- 14595600
TI  - Antitussive potential of methanol extract of stem bark of Ficus racemosa Linn.
AB  - The methanol extract of Ficus racemosa Linn (Moraceae) (stem bark) (MEFR) was
      tested for its antitussive potential against a cough induced model by sulphur
      dioxide gas in mice. The extract demonstrated significant (p < 0.001) antitussive
      activity at all tested dose levels when compared with the control. The
      antitussive activity of the extract was comparable to that of codeine phosphate
      (10 mg), a standard antitussive agent. The extract exhibited maximum inhibition
      of 56.9% at a dose of 200 mg/kg (p.o.) 90 min after administration.

PMID- 14595602
TI  - Screening South Indian medicinal plants for antifungal activity against cutaneous
      pathogens.
AB  - In this study, twenty-eight South Indian medicinal plants were screened for their
      anti-fungal activity against six species of fungi (Trichophyton mentagrophytes,
      T. rubrum, T. soudanense, Candida albicans, Torulopsis glabrata, and C. krusei).
      Three plant species extracts, Celastrus paniculatus, Eriodendron anfractuosum and
      Ficus glomerata showed inhibitory activity. An aqueous extract of galls of
      Terminalia chebula showed inhibitory effects on three dermatophytes (Trichophyton
      spp.) and three yeasts (Candida spp.). Seeds extract of T. chebula inhibited only
      the growth of T. glabrata. An aqueous extract of T. chebula showed inhibitory
      effects higher than those measured in ethanol extracts. It is therefore suggested
      that tannins are plausible candidates for the anti-dermatophytic effects of T.
      chebula. Chebulinic acid, a known tannin of T. chebula was tested and found not
      inhibitory, thus a search for the active compound is needed.

PMID- 14595604
TI  - Herding cats part 2: the plight of female pelvic medicine and reconstructive
      surgery fellowships.

PMID- 14595605
TI  - Motor evoked potentials from the pelvic floor.
AB  - AIMS: Proper function of the lower urinary tract depends on the integrity of the
      central and peripheral nervous pathways on multiple levels, and the complexity of
      this system leaves it susceptible to even minor lesions. While dysfunction of the
      lower urinary tract is prevalent amongst patients with nervous system disease,
      e.g., multiple sclerosis (MS), most women with lower urinary tract dysfunction
      (LUTD) have no overt neurological cause. Refined neuro-diagnostic approaches are
      needed to reveal neurogenicity in these patients. A potential method is
      transcranial magnetic stimulation (TMS), which is used routinely to test the
      motor innervation of limb muscles, but also can be applied to test pelvic floor
      efferents. To resolve the lack of methodological clarity and the need for
      normative values for the use of pelvic floor motor evoked potentials (MEPs), 30
      healthy women and 16 women with MS were studied. METHODS: The healthy women
      underwent MEP studies with various stimulus and recording modalities, and, to
      test reproducibility, 18 of them were retested at a separate session. The women
      with MS underwent MEP testing as well as urodynamic studies. RESULTS: From the
      methodological studies of healthy women, the use of invasive concentric needle
      electrodes was found to be superior to surface electrodes. When applying magnetic
      stimuli over the sacral region, various methodological problems were encountered.
      In the healthy women, a large variability of responses was noted, the long-term
      reproducibility of pelvic floor MEP latencies was poor, and in some cases
      responses could not be obtained. In the study of women with MS, prolonged central
      conduction times were found, along with many cases of unevokable responses, and a
      poor correlation of MEPs to urodynamic findings. The problems of obtaining
      selective recordings from the inaccessible pelvic floor musculature are
      discussed, and possible sources of variability in MEPs from the pelvic floor are
      considered. By relating the findings in the present studies to those of others
      using different modalities, some reflections are presented on the nature of the
      neural pathways to the pelvic floor activated by magnetic stimulation. As
      unevokable responses from the pelvic floor were an occasional finding among the
      healthy women, it is argued that a pelvic floor non-response in a patient with
      suspected corticospinal lesion should be interpreted with care, and should not
      carry the same clinical significance as an absent limb response. CONCLUSIONS: The
      inherent limitations of pelvic floor MEPs are discussed, and it is concluded that
      while there seems to be only limited clinical value of pelvic floor MEP testing,
      there might be some interesting scientific perspectives in studies that aim to
      control and explain the variability of responses.

PMID- 14595606
TI  - Frequency-volume charts: a tool to evaluate bladder sensation.
AB  - AIMS: Bladder sensation is routinely evaluated by cystometric bladder filling and
      electrical stimulation. These methods require catheterization and stimulate the
      bladder artificially. In this study, we evaluated whether frequency-volume charts
      can be used as a non-invasive tool to study bladder sensation during normal daily
      life. Furthermore the agreement between sensory data obtained from frequency
      volume charts and conventional cystometric bladder filling is studied. MATERIALS
      AND METHODS: Fifteen healthy female students filled out frequency-volume charts
      at home and scored the grade of perception of bladder fullness at each
      micturition. They also measured the volume of three voidings after postponing
      micturition as long as possible. Sensation of bladder filling was finally
      evaluated during cystometry. RESULTS: On frequency-volume charts, 65% of all
      voidings was made without desire to void, only 9.5% was with strong desire.
      Urgent desire to void was not reported except after voluntarily postponing
      micturition. Higher grades of perception of fullness were associated with
      significantly higher voided volumes. Mean volumes for the different sensations of
      fullness on the charts were not significantly different from volumes at different
      sensations reported during cystometry. CONCLUSIONS: In conclusion, bladder
      sensation during daily life can be evaluated by scoring the grade of perception
      of fullness on frequency-volume charts. During life voiding usually occurs
      without desire to void. The voided volumes at different sensations of fullness
      are comparable to the volumes at different sensations of filling during
      cystometry. Therefore, frequency-volume charts with evaluation of perception of
      fullness may provide an initial non-invasive tool to study bladder sensation.

PMID- 14595607
TI  - Observations on the function of the female urethra: I: relation between maximum
      urethral closure pressure at rest and urethral hypermobility.
AB  - AIMS: To study the relation between maximum urethral closure pressure at rest and
      urethral hypermobility in female patients. PATIENTS AND METHODS: We selected 255
      patients aged 20 years and older, with a stable bladder on multichannel
      urodynamics, without known neurological pathology, and without a history of
      pelvic or anti-incontinence surgery. A resting urethral pressure profile and the
      degree of urethral hypermobility were registered. Two-tailed analyses of variance
      (ANOVA) with Fisher's post-hoc tests were used to detect any statistically
      significant difference (P < 0.05) in urethral closure pressure between groups
      with varying degrees of urethral hypermobility. RESULTS: Mean age was 45.6 +/-
      12.7 (range 20-77) years. Mean maximum urethral closure pressure for the entire
      group was 62.7 +/- 29 (range 10-150) cm of water. A statistically significant
      inverse relationship was found between age and maximum urethral closure pressure
      (r = 0.489, P < 0.0001) when both analyzed as continuous variables, and with age
      categorized in 10-year increments (P < 0.0001). When comparing mean urethral
      closure pressure in each group examined for urethral hypermobility, a
      statistically significant difference was noted when grades I, II, and III were
      compared to grade 0 hypermobility. No significant difference was observed when
      grades I, II, and III were compared to each other. Even if statistically non
      significant, there exists an inverse relationship between the degree of urethral
      hypermobility and the maximum urethral closure pressure: a higher hypermobility
      is associated with a lesser urethral closure pressure. CONCLUSIONS: Urethral
      closure pressure falls significantly when urethral hypermobility is present. This
      decrease is not related to patient's age or parity. Our observations demonstrate
      an inverse relation between urethral closure pressure and the degree of cysto
      urethrocele. As hypermobility increases, closure pressure decreases, even if this
      decrease does not reach the level of statistical significance.

PMID- 14595608
TI  - Development of a dynamometer for measuring the isometric force of the pelvic
      floor musculature.
AB  - AIMS: The aim of this study was to design and develop a dynamometer providing a
      direct measurement of pelvic floor muscle (PFM) strength. MATERIALS AND METHODS:
      Two pairs of strain gauges were mounted on the moveable branch of a dynamometric
      speculum allowing measurements at different vaginal apertures. Linearity,
      repeatability, independence of the site of application of the resultant force to
      the lower branch of the speculum and hysteresis were tested by means of in vitro
      calibration studies. RESULTS: The linearity proved excellent over a range of 0-15
      N with regression coefficients close to unity between imposed loads and voltage
      outputs. The slopes and intercepts of the regression lines were not significantly
      different between repeated sessions, indicating the high reliability of these in
      vitro measurements. The slopes and intercepts of the calibrations, using the same
      repertoire of loads imposed at three locations on the moving branch of the
      dynamometer, were not significantly different, confirming that the force
      measurement is independent of the site of the force application. Hysteresis was
      considered to be minimal. CONCLUSIONS: This study demonstrates that the
      dynamometer provides reliable measurements. The new device thus appears to have
      conceptual and measuring advantages over conventional methods and seems to be a
      very promising instrument for measuring pelvic floor strength.

PMID- 14595609
TI  - Pelvic floor muscle strength and response to pelvic floor muscle training for
      stress urinary incontinence.
AB  - AIMS: Several randomized controlled trials have demonstrated that pelvic floor
      muscle training is effective to treat stress urinary incontinence. The aim of the
      present study was to compare muscle strength increase and maximal strength in
      responders and non-responders to pelvic floor muscle training. MATERIALS AND
      METHODS: Fifty-two women with urodynamically proven stress incontinence who had
      participated in a six months randomized controlled trial on pelvic floor muscle
      training, mean age 45.4 years (range 24-64), participated in the study. The women
      were classified as responders and non-responders based on a combination of five
      effect variables covering urodynamic measurement, pad test with standardized
      bladder volume, and self-reports. Pelvic floor muscle strength was measured with
      a vaginal balloon connected to a fiber optic micro tip transducer (Camtech AS,
      Sandvika, Norway). RESULTS: There was a positive correlation between improvement
      in PFM maximal strength and improvement measured by leakage index (r = 0.34, P <
      0.01), and reduction in urinary leakage measured by the pad test (r = 0.23, P =
      0.05). The total sample of 52 women comprised 21 responders, 18 unclassifiable,
      and 13 non-responders. There was a statistically significant difference in
      maximal strength after the training period between responders and non-responders;
      24.0 cm H2O (95% CI:18.1-29.9) versus 12.7 cm H2O (95% CI: 6.8-18.6) P < 0.001),
      and strength increase; 14.8 cm H2O (95% CI: 8.9-20.7) versus 5.0 cm H2O (95% CI:
      2.6-12.6), respectively (P = 0.03). CONCLUSIONS: There was a positive relation
      between both pelvic floor muscle strength increase and maximal strength, and
      improvement of stress urinary incontinence.

PMID- 14595610
TI  - Compliance with a pelvic muscle exercise program as a causal predictor of urinary
      stress incontinence amongst Chinese women.
AB  - AIM: To determine the importance and contribution of compliance in a pelvic
      muscle exercise program as a factor in reducing the severity of urinary stress
      incontinence amongst Chinese women. METHODS: Two hundred fourteen women
      presenting with urinary stress incontinence who agreed to undertake a program of
      pelvic muscle exercises were recruited into the study. Incontinence (wetting
      episodes), pelvic muscle strength, exercises compliance, correctness of pelvic
      muscle exercise technique, duration of stress incontinence, and previous history
      of pelvic surgery were recorded on four occasions: baseline (first clinic
      session) and second to fourth clinic sessions. Demographic data were also
      collected at baseline. Stepwise multiple regression analyses were used to
      determine the relative importance of compliance to exercise regime in predicting
      the severity of incontinence. Path analysis was used to provide a summary
      description of the influence of compliance on the outcomes over the four visits.
      RESULTS: The pelvic muscle training program appears to be able to reduce the
      overall urinary incontinence episodes by 85.2% and achieved a 73.1% increase in
      pelvic muscle strength. Although the number of wetting episodes in any visit are
      causally linked to that recorded in previous visit, those who were more compliant
      had a greater reduction. Age, mode of delivery, menopausal status, history of
      pelvic surgery, and duration of incontinence did not appear to contribute
      significantly to predicting incontinence. CONCLUSION: Compliance with pelvic
      muscle exercises significantly contributed to a reduction in urinary stress
      incontinence.

PMID- 14595612
TI  - Urodynamic evaluation of surgical outcome in patients with urinary retention due
      to central lumbar disc prolapse.
AB  - AIMS: To investigate whether acute urinary retention due to central lumbar disc
      prolapse is reversible after emergency spinal surgery. METHODS: Eight patients
      (two males, six females) with a mean age of 31.5 years (range, 18-42 years) with
      urinary retention due to lumbar disc prolapse were studied. An emergency surgery
      was performed within 48 hours (mean, 42 hours) after the onset of urinary
      retention. Urodynamic study was performed before and after the operation.
      RESULTS: All patients had acontractile detrusor without bladder sensation and
      four of seven patients had inactive external sphincter on electromyogram at
      presentation. Two patients were unable to void up to 1 and 5 months after surgery
      and were then lost for follow-up. The remaining six patients could void with
      straining or changing their voiding postures (bending forward), postoperatively.
      A follow-up urodynamic study was performed in all patients from 1 month to 6
      years postoperatively. All patients demonstrated acontractile detrusor on
      cystometrogram. On external sphincter electromyogram, four patients had normal
      activities. The remaining four patients recovered electromyographic activities,
      but two of them had denervation motor unit potentials and two had low activities.
      CONCLUSIONS: Bladder function was irreversible after spinal surgery, whereas
      urethral function showed a better recovery in patients with acute urinary
      retention due to central lumbar disc prolapse. However, most of our patients
      could empty their bladder only by straining or changing their voiding postures
      postoperatively.

PMID- 14595611
TI  - Prevalence and correlations of anal incontinence and constipation in Taiwanese
      women.
AB  - Anal incontinence and constipation are not only physically and psychologically
      disabling symptoms but also a significant social and public health problem. The
      epidemiology of anal incontinence and constipation from community-bases remains
      largely unknown, especially in Asian women. This study is a continuation of a
      previous survey taken on the epidemiology of urinary incontinence and overactive
      bladder in Taiwanese women by using a second questionnaire (correlation
      coefficient for symptoms, r=0.87; P<0.05). We evaluated the prevalence and
      potential risk factors associated with anal incontinence and constipation in the
      general population. Of the 1,584 (2.92%) women sampled, 1,253 (79.1%) were
      successfully interviewed at home. The prevalence of fecal incontinence and flatus
      incontinence was 35 (2.8%) and 107 (8.6%), respectively. There were 306 (24.5%)
      participants who reported constipation. However, according to the current medical
      criteria for constipation, the prevalence of constipation was only 2.7%. The
      prevalence of anal incontinence did not increase after the age of 65 years (9.7%,
      including 3.5% of elderly women with fecal incontinence and 6.2% of elderly women
      with flatus incontinence). The prevalence of constipation significantly increased
      in the women aged 65 years and over (self-reported prevalence: 32.4%, fitted in
      medical criteria for constipation: 8.3%). Our results demonstrated that
      constipation shares some of the same risk factors, namely, symptoms of
      uterovaginal prolapse, prior gynecologic surgery, and overactive bladder that
      predispose women to the occurrence of anal incontinence. The questionnaire needs
      a higher discriminatory capacity, and a longitudinal study should be conducted to
      clarify this conflict further.

PMID- 14595613
TI  - Dissociation between electrical and mechanical bulbocavernosus reflexes.
AB  - AIMS: To record reflex motor responses, elicited by mechanical stimulation of the
      penis or clitoris, in each bulbocavernosus muscles and to compare left and right
      reflex pathways in normal subjects, then to compare electrical and mechanical
      responses in various neurological diseases. METHODS: Two groups of patients were
      studied: 22 patients without neurological disease considered as normal subjects;
      and 25 patients with neurological disease (three multiple sclerosis, six spina
      bifida, nine conus medullaris syndrome, three peripheral neuropathies, two
      lumbosacral lesions, one multisystem atrophy, and one syringomyelia). Electrical
      bulbocavernosus reflex (EBCR) was evoked by orthodromic stimulation of the dorsal
      nerve of the penis at the penile base or the clitoris. Mechanical bulbocavernosus
      reflex (MBCR) was elicited with an electromechanical hammer, tapping directly on
      the clitoris zone or on the ventral part of glans penis. For EBCR and MBCR,
      bulbocavernosus muscle contractions were successively recorded in the left and in
      the right side with a needle inserted under visual guidance. RESULTS: Mean left
      mechanical latency was 31.7 msec (SD = 4.5) and right one 31.6 msec (SD = 3.8).
      The reproducibility of the responses was excellent (P < 0.0001). ). The mean
      difference between left and right latencies was 2 msec (SD = 1.2). In the
      neurological group, 22 EBCR (six right, nine left, seven bilateral) and 19 MBCR
      (eight right, nine left, two bilateral) were considered abnormal. The mean reflex
      latencies in patients with neurological lesions (lower motor neuron lesions) were
      statistically longer (P < 0.0001) than in normal subjects. Exact concordance
      (side of lesion) between MBCR and EBCR was observed in 15/25 cases (60%), poor
      concordance (presence of a sacral reflex alteration) in 3/25 (12%) cases, and in
      7/25 (28%) cases there was a significant difference between the two techniques.
      CONCLUSIONS: MBCR may provide a good alternative for electrical stimulation and
      can be used to evaluate urinary disorders when a neurological etiology is
      suspected. However, the presence of false negatives with MBCR suggest that it may
      be more useful as a screening test.

PMID- 14595614
TI  - Bulbocavernous reflex revisited.

PMID- 14595615
TI  - Bladder-anal reflex.
AB  - AIMS: The purposes of this study were to evaluate the bladder-anal reflex (BAR)
      latency in asymptomatic women and determine the pathway of the reflex using
      selective anesthesia and neuromuscular block. METHODS: Urinary incontinence,
      voiding dysfunction, and pelvic organ prolapse are common problems in women.
      Evaluation of pelvic nerve function often augments the clinical assessment of
      these women. Urethral-anal and clitoral-anal reflex testing have been reported as
      methodologies to assess patients with neurogenic disorders. A bladder-anal reflex
      is also obtainable but has not been reported previously in the literature. Twenty
      two subjects and two patients were recruited for evaluation of the BAR. RESULTS:
      This study has allowed us to estimate reference ranges for BAR latency and
      threshold. We defined the upper limit of these reference ranges as two standard
      deviations above their respective means. For the BAR latency, the upper limit of
      the reference range is 91 msec. Any latency value above this limit should be
      considered abnormal. The upper limit for the BAR threshold reference range is
      37.7 mA. Lower thresholds are not thought to be clinically meaningful due to the
      presence of several low sensory thresholds in this asymptomatic normal
      population. CONCLUSIONS: The BAR was obtainable in asymptomatic women and
      compatible with known anatomy and innervation of the lower urinary tract.

PMID- 14595616
TI  - Preconditioning protects the guinea-pig urinary bladder against ischaemic
      conditions in vitro.
AB  - AIMS: To investigate the ability of ischaemic preconditioning (IPC) to protect
      guinea-pig detrusor from damage caused by a subsequent more prolonged exposure to
      ischaemic conditions. MATERIALS AND METHODS: Smooth muscle strips were mounted
      for tension recording in small organ baths continuously superfused with Krebs'
      solution at 37 degrees C. Ischaemia was mimicked by removing oxygen and glucose
      from the superfusing solution. Contractile responses to electrical field
      stimulation (EFS) and carbachol were monitored. Three regimes of preconditioning
      were examined: 15, 10, and 5 min of ischaemic conditions followed by 15, 10, and
      5 min of normal conditions, respectively. RESULTS: Without preconditioning, nerve
      mediated responses were significantly and proportionally reduced by periods of
      ischaemic conditions lasting for 45, 60, and 90 min, but recovered fully after
      exposure to ischaemic conditions for 30 min. The recovery of the responses to EFS
      was significantly improved in preconditioned strips when the period of ischaemic
      conditions was 45 or 60 min. However, no significant differences were seen with
      preconditioning when the period of ischaemic conditions was 90 min. The recovery
      of responses to carbachol was much greater than for the responses to EFS, and no
      significant differences were found between control and preconditioned strips.
      CONCLUSIONS: It is suggested that in vivo short periods of transient ischaemia
      may be able to protect the guinea-pig bladder from the impairment associated with
      longer periods of ischaemia and reperfusion, which might happen in obstructed
      micturition. Our results also indicate that the phenomenon affects mainly the
      intrinsic nerves, which are more susceptible to ischaemic damage than the smooth
      muscle.

PMID- 14595617
TI  - Urinary bladder hyperreflexia: a rat animal model.
AB  - In this work, we are presenting a rat animal model for bladder hyperreflexia
      after suprasacral spinal cord transection. Our aim was to standardize an animal
      model that can be useful in studying this condition. After standardizing the
      animal model in a pilot study, 26 female Sprague-Dawley rats were subjected to
      spinal cord transection at the level of T10 vertebra. Four animals were subjected
      to cystometrogram (CMG) 24 hr after spinalization and six rats 3 weeks post
      spinalization. These CMGs were compared to that of six normal controls. The
      detailed description of the model presented in this manuscript, is the final
      result after several modifications. All the animals consistently developed
      hyperreflexia after an initial period of spinal shock phase. Expressed volume of
      urine continued to decrease until it reached a plateau after peaking at 1-week
      post-spinalization. The attrition rate reached 27.3% after several improvements
      in the animal model and was mostly from self-inflicted injuries. Post-operative
      complications included hypothermia, decubitus ulcers, hematuria, urinary tract
      infection in addition to the unexplained death of two animals. In conclusion, we
      believe that this animal model closely resembles the clinical condition of
      hyperreflexia and follows similar course. The relative low cost of this animal
      model and the easy maintenance makes it a valuable tool to study such a
      condition.

PMID- 14595620
TI  - Ruthenium-catalyzed cyclizations: more than just olefin metathesis!

PMID- 14595621
TI  - Fifty years of Ziegler catalysts: consequences and development of an invention.

PMID- 14595622
TI  - The ethylene polymerization with Ziegler catalysts: fifty years after the
      discovery.
AB  - Fifty years ago, Karl Ziegler and his co-workers discovered the synthesis of
      polyethylenes at low pressures and moderate high temperatures with transition
      metal catalysts of the 4th group and aluminum organic compounds as cocatalysts.
      The last 50 years represent a story of innovations in science and industry in the
      development of high-activity catalysts and processes based on a detailed
      understanding of all relevant chemical and physical processes on all scales.
      Catalysts, technologies, and products are still under further development, which
      shows that the potential of this polymerization process is not fully exploited.
      Today's targets include achieving better product properties at lower production
      costs and the substitution of other materials, such as glass, paper, steel, and
      concrete in certain fields because polyethylenes deliver better resource-saving
      solutions.

PMID- 14595623
TI  - Reversible insulator-to-metal transition in p+-type mesoporous silicon induced by
      the adsorption of ammonia.

PMID- 14595624
TI  - Colloidal two-dimensional systems: CdSe quantum shells and wells.

PMID- 14595625
TI  - Trapping cations in specific positions in tuneable "artificial cell" channels:
      new nanochemistry perspectives.

PMID- 14595626
TI  - On the mechanism of the anionic oxy-cope rearrangement of trans-1,2
      dialkenylcyclobutanols.

PMID- 14595627
TI  - Recovering methane from solid methane hydrate with carbon dioxide.

PMID- 14595628
TI  - A general method for the direct alpha-arylation of nitriles with aryl chlorides.

PMID- 14595629
TI  - A highly active and selective catalyst system for the Baylis-Hillman reaction.

PMID- 14595630
TI  - Enantioselective alkynylation of aromatic ketones catalyzed by chiral
      camphorsulfonamide ligands.

PMID- 14595631
TI  - A modular approach to oxoindolizino quinolines: efficient synthesis of mappicine
      ketone (nothapodytine B).

PMID- 14595632
TI  - Enantioselective radical addition to N-acyl hydrazones mediated by chiral Lewis
      acids.

PMID- 14595633
TI  - The dual roles of oxodiperoxovanadate both as a nucleophile and an oxidant in the
      green oxidation of benzyl alcohols or benzyl halides to aldehydes and ketones.

PMID- 14595634
TI  - [Cp*(eta2-bipy)(MeCN)RuII][PF6] catalysts for regioselective allylic substitution
      and characterization of dicationic [Cp*(eta2-bipy)(eta3-allyl)RuIV][PF6]2
      intermediates.

PMID- 14595635
TI  - Development of a novel sugar linkage: 6,6'-ether-connected sugars.

PMID- 14595636
TI  - Site titration with organic bases during catalysis: selectivity modifier and
      structural probe in methanol oxidation on Keggin clusters.

PMID- 14595637
TI  - Homogeneous ethylene-polymerization catalysts based on alkyl cations of the rare
      earth metals: are dicationic mono(alkyl) complexes the active species?

PMID- 14595639
TI  - Elemental gallium as a source of subvalent gallium units in gallium-rhodium
      clusters.

PMID- 14595638
TI  - Ligands for palladium-catalyzed cross-couplings of alkyl halides: use of an
      alkyldiaminophosphane expands the scope of the Stille reaction.

PMID- 14595641
TI  - Microkinetic videomicroscopic analysis of olefin polymerization with a supported
      metallocene catalyst.

PMID- 14595640
TI  - A gas-phase reaction as a functional model for the activation of carbon dioxide
      by carbonic anhydrase.

PMID- 14595642
TI  - Carbonylbiscaprolactam: a versatile reagent for organic synthesis and isocyanate
      free urethane chemistry.

PMID- 14595644
TI  - Sickle cell disease and stroke: primary prevention and transcranial Doppler.

PMID- 14595645
TI  - Brain injury in children with sickle cell disease: prevalence and etiology.
AB  - Our objective was to evaluate the relationship between brain injury by magnetic
      resonance imaging (MRI) and vasculopathy by magnetic resonance angiography (MRA)
      in children with hemoglobin SS, the most serious form of sickle cell disease. We
      reviewed imaging for all 146 SS patients imaged at St. Jude Children's Research
      Hospital since 1993. Standard MRI criteria were used to identify cystic
      infarction, leukoencephalopathy, encephalomalacia, or atrophy. Standard MRA
      criteria were used to identify arterial tortuousity (limited vasculopathy), and
      stenosis or occlusion (extensive vasculopathy). At an average age of 10 years,
      the estimated prevalence of infarction, ischemic damage, or atrophy in SS
      patients was 46%, and of vasculopathy was 64%. Only 28% of patients were normal
      by both modalities, and patients abnormal by MRA often were abnormal by MRI (p <
      0.00001). Patients with cystic infarction had limited vasculopathy, whereas
      patients with encephalomalacia had stenosis or occlusion (p < 0.0001). Large
      arteries were affected in 31% of brain injury patients, whereas small arteries
      are inferred to be abnormal in up to 69% of patients with brain injury. The
      degree of vasculopathy is closely related to the degree of brain injury, implying
      that vasculopathy is prodromal to most forms of brain injury in hemoglobin SS.

PMID- 14595646
TI  - Variable phenotypic expression and extensive tau pathology in two families with
      the novel tau mutation L315R.
AB  - Mutations in the tau gene cause familial frontotemporal dementia and parkinsonism
      linked to chromosome 17. Here, we describe two Dutch families with familial
      frontotemporal dementia associated with the novel missense mutation L315R in exon
      11 of tau. The age at onset of disease showed a large variation within each
      family, ranging from 25 to 64 years. Incomplete penetrance was established in an
      82-year-old mutation carrier with no signs of dementia and appeared probable in
      two additional subjects. The brains of two affected subjects were studied and
      showed extensive tau pathology in neurons (Pick-like inclusions) and astroglial
      cells, particularly in the frontotemporal cortex and the hippocampal formation.
      Sarkosyl-insoluble tau extracted from the cerebral cortex showed the presence of
      straight and twisted tau filaments and a pattern of pathological tau bands
      similar to that of Pick's disease. Upon dephosphorylation, only five of the six
      brain tau isoforms were observed, with the shortest isoform being undetectable.
      All six tau isoforms were present in soluble brain tau. Recombinant tau proteins
      with the L315R mutation showed a reduced ability to promote microtubule assembly.

PMID- 14595648
TI  - Ischemia triggered by spreading neuronal activation is induced by endothelin-1
      and hemoglobin in the subarachnoid space.
AB  - Delayed cerebral vasospasm has a major impact on the outcome of subarachnoid
      hemorrhage. Two important candidates to cause the arterial spasm are the red
      blood cell product oxyhemoglobin and the vasoconstrictor endothelin-1, although
      oxyhemoglobin alone is not sufficient to induce cerebral ischemia and endothelin
      1 leads to ischemia only at relatively high concentrations. In this study, we
      demonstrated that the combination of oxyhemoglobin and endothelin-1 triggered
      spreading neuronal activation in rat cortex in vivo. In contrast with the
      expected transient increase of regional cerebral blood flow during spreading
      depression, however, cerebral blood flow decreased profoundly and was long
      lasting, paralleled by delayed repolarization of the steady (direct current)
      potential. These changes are characteristic of cortical spreading ischemia.
      Replacing oxyhemoglobin for the nitric oxide synthase inhibitor Nomega-nitro-L
      arginine mimicked these effects, implicating nitric oxide scavenging functions of
      oxyhemoglobin. Furthermore, the effect of endothelin-1 was related to a reduction
      of Na(+)-/K(+)-ATPase activity rather than solely to its vasoconstrictive
      properties. In conclusion, the threshold concentration of endothelin-1 that
      induces cerebral ischemia is profoundly reduced via a complex interaction between
      the neuronal/astroglial network and the cortical microcirculation if nitric oxide
      availability declines. The results may have implications for the understanding of
      subarachnoid hemorrhage-related cortical lesions.

PMID- 14595649
TI  - Presence of reactive microglia in monkey substantia nigra years after 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine administration.
AB  - This report describes the presence of reactive microglia, the accumulation of
      extracellular melanin, and the extensive loss of dopaminergic neurons in the
      substantia nigra of monkeys administered 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP) 5 to 14 years before death. This evidence of chronic
      neuroinflammation years after MPTP exposure is similar to that previously
      reported in humans. The monkeys were drug free for at least 3 years before death,
      indicating that a brief exposure to MPTP had instituted an ongoing inflammatory
      process. The mechanism is unknown but could have important implications regarding
      the cause of Parkinson's disease and possible approaches to therapy.

PMID- 14595647
TI  - Mechanisms of stroke protection by physical activity.
AB  - Regular physical activity is associated with a decrease of cerebrovascular and
      cardiovascular events, which may relate to enhanced endothelium-dependent
      vasodilation. Here, we provide evidence that physical activity protects against
      ischemic stroke via mechanisms related to the upregulation of endothelial nitric
      oxide synthase (eNOS) in the vasculature. Voluntary training on running wheels or
      exercise on a treadmill apparatus for 3 weeks, respectively, reduced cerebral
      infarct size and functional deficits, improved endothelium-dependent
      vasorelaxation, and augmented cerebral blood flow in wild-type mice. The
      neuroprotective effects of physical training were completely absent in eNOS
      deficient mice, indicating that the enhanced eNOS activity by physical training
      was the predominant mechanism by which this modality protects against cerebral
      injury. Our results suggest that physical activity not only decreases stroke
      risk, but also provides a prophylactic treatment strategy for increasing blood
      flow and reducing brain injury during cerebral ischemia.

PMID- 14595650
TI  - Growth hormone prevents human immunodeficiency virus-induced neuronal p53
      expression.
AB  - Growth hormone (GH) is neuroprotective, presumably through its actions on GH
      receptor-mediated pathways. Here, we examined the effects of GH using in vitro
      and in vivo assays of human immunodeficiency virus (HIV)-induced neuronal injury.
      Neuronal cultures were in assays of neurotoxicity induced by supernatants from
      HIV-1 tat-transfected monocytoid cells (Tat supernatant). GH treatment reduced
      neuronal death compared with untreated cultures (p < 0.001), which was blocked by
      a GH receptor antagonist, B2036. Tat supernatant-induced p53 expression in
      neurons was also reduced by GH treatment. Expression of both p53 and GH receptor
      were increased in brain tissue from HIV-infected persons compared with controls
      (p < 0.05). Mice receiving intrastriatal implants of Tat supernatant and treated
      with GH showed less neurobehavioral abnormalities together with reduced
      neuroinflammation and neuronal injury compared with untreated animals (p < 0.01).
      Three acquired immunodeficiency syndrome-defined patients with neurocognitive
      impairment were serially evaluated during daily GH treatment showing a sustained
      improvement in neuropsychological performance (p < 0.01). GH prevents neuronal
      death through its actions on neurons involving a p53-mediated pathway and also
      improved in vivo neurological function, indicating that GH may have a role in the
      treatment of HIV-induced neurodegeneration.

PMID- 14595651
TI  - Reappraisal of the human vestibular cortex by cortical electrical stimulation
      study.
AB  - The cortical areas with vestibular input in humans were assessed by electrical
      stimulation in 260 patients with partial epilepsy who had undergone stereotactic
      intracerebral electroencephalogram recordings before surgery. Vestibular symptoms
      were electrically induced on 44 anatomical sites in 28 patients. The patients
      experienced illusions of rotation (yaw plane: 18, pitch plane: 6, roll plane: 6),
      translations (n = 6), or indefinable feelings of body motion (n = 8). Almost all
      vestibular sites were located in the cortex (41/44): in the temporal (n = 19),
      parietal (n = 14), frontal (n = 5), occipital (n = 2), and insular (n = 1) lobes.
      Among these sites, we identified a lateral cortical temporoparietal area we
      called the temporo-peri-Sylvian vestibular cortex (TPSVC), from which vestibular
      symptoms, and above all rotatory sensations, were particularly easily elicited
      (24/41 cortical sites, 58.5%). This area extended above and below the Sylvian
      fissure, mainly inside Brodmann areas 40, 21, and 22. It included the parietal
      operculum (9/24 TPSVC sites) which was particularly sensitive for eliciting pitch
      plane illusions, and the mid and posterior part of the first and second temporal
      gyri (15/24 TPSVC sites) which preferentially caused yaw plane illusions. We
      suggest that the TPSVC could be homologous with the monkey's parietoinsular
      vestibular cortex.

PMID- 14595652
TI  - Interictal EEG discharges, reproductive hormones, and menstrual disorders in
      epilepsy.
AB  - We evaluated reproductive endocrine function in women with unilateral
      temporolimbic epilepsy and normal control subjects to assess the effects of
      epilepsy, epilepsy laterality, and antiepileptic drug use on the cerebral
      regulation of hormonal secretion. The findings indicate that reproductive
      endocrine function differs between women with epilepsy and normal control
      subjects. Significant differences exist at all levels of the reproductive
      neuroendocrine axis, that is, hypothalamus, pituitary, and peripheral gland.
      Differences show significant relationships to the epilepsy itself as well as to
      medication use. Reproductive neuroendocrine changes occur in a stochastic manner
      such that the laterality of unilateral temporolimbic discharges is associated
      with predictable directional changes in hormonal secretion at all levels of the
      reproductive neuroendocrine axis. These directional changes are consistent with
      the finding that different reproductive disorders may develop in relation to left
      and right-sided temporolimbic epilepsy. Hormonal changes can show close temporal
      relationship to the occurrence of interictal epileptiform discharges and may vary
      in relation to the laterality of the discharges. Antiepileptic drugs differ in
      their effects on reproductive hormone levels. There are notable differences
      between enzyme-inducing and noninducing drugs. Menstrual disorders are more
      common among women with interictal discharges as well as women with abnormal
      hormonal findings.

PMID- 14595653
TI  - CCR1 is an early and specific marker of Alzheimer's disease.
AB  - Chemokines are a diverse group of small proteins that effect cell signaling by
      binding to G-protein-coupled, seven-trans-membrane receptors. Our group had found
      previously that the chemokine receptor CCR1 was present in neurons and dystrophic
      processes in a small sample of Alzheimer's disease cases. This expanded
      immunohistochemical study shows that the number of CCR1-positive plaque-like
      structures in the hippocampus and entorhinal cortex is highly correlated to
      dementia state as measured by the clinical dementia rating score. CCR1
      immunoreactivity is found in dystrophic, neurofilament-positive, synaptophysin
      negative neurites that are associated with senile plaques containing amyloid beta
      peptides of the 1-42 species (Abeta42). CCR1 was not, however, associated with
      diffuse deposits of Abeta42. There was limited expression of CCR1 in
      neurofibrillary tangle-bearing neuritic processes. Astrocytes and microglia were
      typically negative for CCR1. Human brains from age-matched, nondemented
      individuals rarely displayed either CCR1 or Abeta42 immunoreactivity. Seven other
      types of dementing neurodegenerative diseases were examined, and all failed to
      demonstrate CCR1 immunopositivity unless Abeta42-positive plaques were also
      present. Thus, neuronal CCR1 is not a generalized marker of neurodegeneration.
      Rather, it appears to be part of the neuroimmune response to Abeta42-positive
      neuritic plaques.

PMID- 14595654
TI  - Valproic acid increases SMN levels in spinal muscular atrophy patient cells.
AB  - Spinal muscular atrophy (SMA) is an inherited motor neuron disease caused by
      mutation of the telomeric copy of the survival motor neuron gene (SMN1). Although
      a centromeric copy of the survival motor neuron gene (SMN2) is retained in all
      patients with SMA, it differs from SMN1 at a critical nucleotide such that the
      majority of SMN2 transcripts lack exon 7 and encode an unstable, truncated
      protein. Here, we show that valproic acid increases levels of exon 7-containing
      SMN transcript and SMN protein in type I SMA patient-derived fibroblast cell
      lines. Valproic acid may increase SMN levels both by activating the SMN promoter
      and by preventing exon 7 skipping in SMN transcripts. Valproic acid and related
      compounds warrant further investigation as potential treatment for SMA.

PMID- 14595655
TI  - Protective role of tuftsin fragment 1-3 in an animal model of intracerebral
      hemorrhage.
AB  - Intracerebral hemorrhage (ICH) causes morbidity and mortality and commonly
      follows the reperfusion after an ischemic event. Tissue plasminogen activator
      (tPA), a fibrinolytic serine protease, is routinely given for the treatment of
      stroke. However, tPA also can promote neuronal death, suggesting that caution
      should be exercised when using it. Furthermore, tPA upon brain injury mediates
      microglial activation and modulates neuronal survival. To investigate the role of
      tPA and microglia during brain hemorrhage, we induced experimentally ICH by
      intracerebral injection of collagenase. Seven days after the introduction of ICH,
      it persisted in tPA-deficient (tPA(-/-)) mice but is drastically reduced in size
      in wild-type mice. Three weeks after ICH, there are still red blood cells in tPA(
      /-) but not in wild-type animals. Activated microglia persist around the injury
      site. When microglial activation is inhibited by tuftsin fragment 1-3
      macrophage/microglial inhibitory factor (MIF), the stroke injury volume is
      significantly reduced, and the neurobehavioral deficits exhibited by the mice are
      improved. Our results suggest that endogenous tPA assists in the clearance of
      intracerebral hemorrhage, presumably by affecting microglial activation, and MIF
      could be a valuable neuroprotective agent for the treatment of ICH.

PMID- 14595656
TI  - Impaired complex I assembly in a Leigh syndrome patient with a novel missense
      mutation in the ND6 gene.
AB  - We describe a novel mutation in the ND6 gene (T14487C) in a patient with Leigh
      syndrome. Biochemical analyses indicated a low complex I activity in the
      patient's fibroblasts but normal values in muscle and liver. Cybrid clones showed
      a specific complex I defect that correlates with the mutant heteroplasmy levels.
      Additionally, we demonstrate an altered mobility and a decrease in the levels of
      fully assembled complex I in the patient's fibroblasts and cybrids, suggesting
      that the mutation has a profound effect on complex I assembly and/or stability.

PMID- 14595657
TI  - Functional neuroimaging provides evidence of anomalous cerebral laterality in
      adults with Klinefelter's syndrome.
AB  - This study aimed to characterize cerebral perfusion in men with Klinefelter's
      syndrome, known to present specific deficits in language, using (99m)Tc-
      hexamethylpropylene-amine-oxime scintigraphy and Talairach normalization. While a
      perfusion asymmetry toward the left hemisphere was found in controls, perfusion
      was mostly symmetrical in Klinefelter patients in the upper temporal and lower
      parietal areas. Scores on verbal tests were inversely correlated with perfusion
      changes, providing neurobiological substrate of anomalous cerebral laterality.

PMID- 14595658
TI  - On symptomatic heterozygous alpha-sarcoglycan gene mutation carriers.
AB  - Mutations in the human alpha-sarcoglycan gene on chromosome 17q21.2 have been
      shown to cause a severe childhood autosomal recessive muscular dystrophy, a less
      severe limb girdle muscular dystrophy, exercise intolerance, or asymptomatic
      hyperCKemia. Here, we describe the clinical findings in a German family harboring
      a 371 T > C (Ile124Thr) missense mutation in the alpha-sarcoglycan gene. Whereas
      our index patient, an 11-year-old girl homozygous for this mutation, presented
      with a severe Duchenne-like phenotype, 7 out of 12 heterozygous mutation carriers
      from three generations showed mild to moderate scapular winging. In analogy to
      symptomatic female dystrophinopathy carriers, our results suggest that
      heterozygous alpha-sarcoglycan gene mutation carriers can be symptomatic with
      selective muscle weakness. This finding may be attributed to an additional
      negative variation in a yet unknown modifier gene essential to the function of
      the sarcoglycan complex in shoulder girdle muscles.

PMID- 14595659
TI  - Dually infected (HSV-1/VZV) single neurons in human trigeminal ganglia.
AB  - Human trigeminal ganglia were tested by double fluorescence in situ hybridization
      for the presence and distribution of herpes simplex virus type 1 (HSV-1) and
      varicella-zoster virus (VZV) latency. Latency transcripts of both viruses were
      detected in common areas within the ganglia. Also, a few single neurons were
      shown to harbor HSV-1 and VZV together.

PMID- 14595660
TI  - An English kindred with a novel recessive tauopathy and respiratory failure.
AB  - We present the clinicopathological features of two siblings from a consanguineous
      marriage who presented with respiratory hypoventilation and died 10 days and 4
      years later, respectively. This disorder showed extensive tau neuropathology, and
      both had a novel homozygous S352L tau gene mutation. This is the first
      description of a pathologically proved young-onset tauopathy with apparent
      recessive inheritance.

PMID- 14595662
TI  - Edward H. Lambert, MD, PhD: 1915-2003.

PMID- 14595664
TI  - Real-PET and CONSORT.

PMID- 14595661
TI  - Monitoring of 4-hydroxybutyric acid levels in body fluids during vigabatrin
      treatment in succinic semialdehyde dehydrogenase deficiency.
AB  - We report the successful treatment using low-dose vigabatrin (21.5-34 mg/kg/day)
      of a 10-year-old girl with succinic semialdehyde dehydrogenase (SSADH) deficiency
      We verified that 4-hydroxybutyric acid (GHB) concentrations in serum,
      cerebrospinal fluid, and urine continuously decreased in parallel with
      significant clinical improvement. Our results suggest that GHB quantification in
      physiological fluids may be a useful laboratory parameter for monitoring efficacy
      of vigabatrin treatment in SSADH deficiency.

PMID- 14595670
TI  - Intracellular cargo delivery using tat peptide and derivatives.
AB  - Efficient delivery of therapeutic and diagnostic agents across the plasma
      membrane is crucial in developing novel therapies. Membrane permeating peptides,
      in particular HIV-1 tat peptide and its derivatives, have enabled the
      intracellular delivery of cargos of various sizes and physicochemical properties.
      This review summarizes the current knowledge of tat-derived cell permeating
      peptides in the transduction of exogenous molecules/complexes.

PMID- 14595671
TI  - Clinical significance of urokinase-type plasminogen activator receptor (uPAR)
      expression in cancer.
AB  - The involvement of the urokinase-type plasminogen activator (uPA) system in
      particular has been extensively studied in the pathogenesis of cancer. The
      molecular role of the uPA receptor (uPAR) is well characterized with its
      participation in cell migration and extracellular matrix (ECM) degradation. Over
      expression of uPAR in cancer has been demonstrated in many studies and is
      considered an attractive target for anticancer agents. We and others have down
      regulated uPAR expression in an attempt to inhibit cancer metastasis based on its
      molecular role. Uniquely, uPAR which is a glycosyl phosphatidylinositol anchored
      protein is not only bound to the cell surface but also has a soluble form, suPAR.
      There is now accumulated clinical and experimental evidence supporting the
      significant role of uPAR and its soluble counterpart in a number of solid
      cancers. The expression of uPAR can be associated with tumor cells or stromal
      cells or both. Differences observed in the expression of uPAR using
      immunohistochemistry (IHC) are likely explained by the use of different
      antibodies and techniques rather than true cellular differences and are reviewed
      here. This review summarizes the clinical relevance of uPAR and its soluble form
      in the prognosis and diagnosis of different cancers.

PMID- 14595672
TI  - The thioredoxin system--from science to clinic.
AB  - The thioredoxin system-formed by thioredoxin reductase and its characteristic
      substrate thioredoxin-is an important constituent of the intracellular redox
      milieu. Interactions with many different metabolic pathways such as DNA
      synthesis, selenium metabolism, and the antioxidative network as well as
      significant species differences render this system an attractive target for
      chemotherapeutic approaches in many fields of medicine-ranging from infectious
      diseases to cancer therapy. In this review we will present and evaluate the
      preclinical and clinical results available today. Current trends in drug
      development are emphasized.

PMID- 14595673
TI  - Chemistry, biological activity, and chemotherapeutic potential of betulinic acid
      for the prevention and treatment of cancer and HIV infection.
AB  - 3beta-Hydroxy-lup-20(29)-en-28-oic acid (betulinic acid) is a pentacyclic lupane
      type triterpene that is widely distributed throughout the plant kingdom. A
      variety of biological activities have been ascribed to betulinic acid including
      anti-inflammatory and in vitro antimalarial effects. However, betulinic acid is
      most highly regarded for its anti-HIV-1 activity and specific cytotoxicity
      against a variety of tumor cell lines. Interest in developing even more potent
      anti-HIV agents based on betulinic acid has led to the discovery of a host of
      highly active derivatives exhibiting greater potencies and better therapeutic
      indices than some current clinical anti-HIV agents. While its mechanism of action
      has not been fully determined, it has been shown that some betulinic acid analogs
      disrupt viral fusion to the cell in a post-binding step through interaction with
      the viral glycoprotein gp41 whereas others disrupt assembly and budding of the
      HIV-1 virus. With regard to its anticancer properties, betulinic acid was
      previously reported to exhibit selective cytotoxicity against several melanoma
      derived cell lines. However, more recent work has demonstrated that betulinic
      acid is cytotoxic against other non-melanoma (neuroectodermal and malignant brain
      tumor) human tumor varieties. Betulinic acid appears to function by means of
      inducing apoptosis in cells irrespective of their p53 status. Because of its
      selective cytotoxicity against tumor cells and favorable therapeutic index, even
      at doses up to 500 mg/kg body weight, betulinic acid is a very promising new
      chemotherapeutic agent for the treatment of HIV infection and cancer.

PMID- 14595674
TI  - Update on HIV resistance and resistance testing.
AB  - The introduction of highly active antiretroviral therapy, including a combination
      of antivirals directed at various steps in the viral life cycle, has led to
      significant decreases in morbidity and mortality associated with human
      immunodeficiency virus (HIV-1) infections. Despite the availability of numerous
      antivirals, many extensively treated patients gradually loose the ability to
      control viral replication because of development of antiviral resistance.
      Laboratory tests have been developed and validated to assist in recognizing such
      resistance and to help predict which antivirals may be more likely to control
      viral replication in a given patient. Both genotypic and phenotypic assays have
      been developed to assess HIV-1 antiviral resistance. The assay methodologies,
      including the advantages and disadvantages of each method, as well as the
      limitations of each method are reviewed. The ability to predict likely drug
      response from a genotype or a phenotype is continually evolving, and the more
      recently discovered mutation/drug resistance associations are discussed in terms
      of their implications for HIV resistance assays. To provide additional options
      for those who have developed resistance to all currently available drugs, new
      antivirals, such as the fusion inhibitors, are being developed. These new classes
      of antivirals block the HIV viral life cycle at sites other than reverse
      transcriptase and protease. Unique and novel resistance assays are being
      developed to measure HIV resistance to these new drugs.

PMID- 14595675
TI  - Highly sensitive and simple fluorescence staining of proteins in sodium dodecyl
      sulfate-polyacrylamide-based gels by using hydrophobic tail-mediated enhancement
      of fluorescein luminescence.
AB  - Fluorescein has an extremely low luminescence intensity in acidic aqueous media.
      However, when it was bound to proteins, subsequent increase of luminescence
      intensity took place. Furthermore, when a hydrophobic tail, such as aliphatic
      hydrocarbons, was introduced to fluorescein, more dramatic increase of
      luminescence intensity was observed upon binding to proteins. In the present
      study, by utilizing this luminescence enhancement, three hydrophobic fluorescein
      dyes (5-dodecanoyl amino fluorescein, 5-hexadecanoyl amino fluorescein, and 5
      octadecanoyl amino fluorescein) were examined as noncovalent fluorescent stains
      of protein bands in sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      (SDS-PAGE). Effective incorporation of the dyes to proteins in gels was
      accomplished either simply by adding dyes at the protein fixation step, or by
      treating gels with a staining solution after the fixation. The sensitivity of
      this staining method using the fluorescein derivatives was approximately 1
      ng/band for most proteins. For some cases, protein bands containing as low as 0.1
      ng were successfully visualized. In addition, the detection sensitivity showed
      much less protein-to-protein variation than silver staining. This new staining
      method was also successfully applied to two-dimensional electrophoresis of rat
      brain proteins. Its overall sensitivity was comparable to that of silver
      staining.

PMID- 14595676
TI  - Detection of metals in proteins by means of polyacrylamide gel electrophoresis
      and laser ablation-inductively coupled plasma-mass spectrometry: application to
      selenium.
AB  - The capabilities of laser ablation-inductively coupled plasma-mass spectrometry
      for the detection of trace elements in a gel after gel electrophoresis were
      systematically studied. Figures of merit, such as limit of detection, linearity,
      and repeatability, were evaluated for various elements (Li, V, Cr, Mn, Ni, Cu,
      Zn, As, Se, Mo, Pd, Ag, Cd, Pt, Tl, Pb). Two ablation strategies were followed:
      single hole drilling, relevant for ablation of spots after two-dimensional (2-D)
      separations, and ablation with translation, i.e., on a line, relevant for one
      dimensional (1-D) separations. This technique was applied to the detection of
      selenoproteins in red blood cells extracts after a 1-D separation (sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis) and the detection of selenium
      containing proteins in yeast after 2-D electrophoresis (2-DE). The detection
      procedure was further improved by using the dynamic reaction cell technology,
      which allowed the removal of the Ar_2(+) interference and hence the use of the
      most abundant Se isotope, (80)Se. Reaction gases were compared (methane, carbon
      monoxide, ammonia, oxygen and the combination of argon (collision gas) and
      hydrogen (reaction gas)). In each instance, the reaction cell parameters were
      optimized in order to obtain the lowest detection limit for Se (as (80)Se(+),
      (82)Se(+) or (77)Se(+); and as (80)Se(16)O(+), (82)Se(16)O(+) or (77)Se(16)O(+)
      with O(2) as the reaction gas). Carbon monoxide was found to offer the best
      performance. The detection limit with the use of DRC and He as transport gas was
      0.07 microg Se g(-1) gel with single hole drilling and 0.15 microg Se g(-1) gel
      for ablation with translation.

PMID- 14595677
TI  - Electrophoretic dynamics of large DNA stars in polymer solutions and gels.
AB  - We have developed a procedure for synthesizing large stable branched DNA
      structures that enables visualization via fluorescence microscopy. Using this
      procedure we have synthesized large DNA stars and observed their electrophoretic
      behavior in polymer solutions and gels. In dilute polyacrylamide solutions, the
      DNA stars move as random coils and appear to experience only brief collisions
      with the polymer chains in solution. The effect of polymer solution concentration
      on the electrophoretic mobility of stars in the dilute regime is found to be in
      good accord with predictions of the transient entanglement coupling (TEC) model.
      In semidilute polymer solutions, the star arms extend in the field direction and
      drag the core through the matrix. The star arms form several U-shaped
      conformations as they collide and engage with polyacrylamide chains. The U-shaped
      conformations occasionally evolve into J-shaped conformations as the star arms
      slide off the matrix chains they engage during electrophoretic migration. In
      concentrated polymer solutions, the arms of the star extend and form V-shaped
      structures with the core as the apex. The arms then pull the core through the
      matrix. These V-shaped conformations are much longer-lived than U-shaped ones
      and, unlike the latter, do not transform to J-shaped conformations. In
      polyacrylamide and agarose gels, where matrix entanglements are fixed, DNA stars
      become trapped when entanglements with matrix molecules prevent the core from
      being pulled through the matrix by the extended arms. This trapping was observed
      at all gel concentrations and electric fields studied.

PMID- 14595678
TI  - Free solution mobility of small single-stranded oligonucleotides with variable
      charge densities.
AB  - The free solution mobilities of six single-stranded 16-nucleotide DNA oligomers
      with the same sequence, containing up to 11 neutral phosphoramidate
      internucleoside linkages, have been measured by capillary electrophoresis. The
      mobilities of the partially charged oligomers increase linearly with the
      logarithm of increasing charge density, as predicted by the Manning theory of
      electrophoresis (G. S. Manning, J. Phys. Chem. 1981, 85, 1506-1515). For
      comparison, the mobilities of eight fully charged single-stranded oligomers
      containing similar numbers of charged phosphate residues have also been measured.
      The mobilities of the variable length, fully charged oligomers increase more
      rapidly with the increasing number of charged phosphate residues than the
      mobilities of the constant size, partially charged phosphoramidate derivatives,
      because of the larger diffusion coefficients of the modified oligomers.

PMID- 14595679
TI  - Microarray-based resequencing by apyrase-mediated allele-specific extension.
AB  - We have developed an array-based resequencing method to determine genetic
      alterations in putative cancer genes. The method relies on that the specificity
      of DNA polymerase in allele-specific extensions can be enhanced by terminating
      the extension reactions with apyrase and that a tiling set of primers are
      synthesized covering the investigated gene sequence. We report on such apyrase
      mediated allele-specific primer extension (AMASE) assay as a method suitable for
      high-throughout resequencing and mutation detection in tumor suppressor genes and
      oncogenes. In the experimental setup, primers complementary to codons 12, 13 and
      codon 61 of the N-ras proto-oncogene were spotted onto glass slides. Overlapping
      sense and anti-sense primers were designed so that complementary primers for all
      possible mutations in each base position were investigated. The extension
      reactions were performed in a single step following hybridization of target DNA
      to the immobilized primers on the array surface. Mutation detection limits and
      the possibility of quantifying the mutations were investigated using synthetic
      oligonucleotides. In addition, 64 clinical samples were sequenced and 16 of these
      showed mutations in the N-ras gene.

PMID- 14595680
TI  - On-column concentration and separation of double-stranded DNA by gradient
      capillary electrophoresis.
AB  - We describe the separation of dsDNA by capillary electrophoresis in the presence
      of electroosmotic flow (EOF) using poly(ethylene oxide) (PEO). Using 1.0% PEO,
      the separation of DNA fragments with sizes ranging from 51 bp to 23 kbp has been
      achieved in less than 12 min, which is better than conventional methods (in the
      absence of EOF) in terms of speed and resolution. In order to concentrate and
      separate the DNA sample, gradient changes in the concentrations of PEO and
      ethidium bromide (EtBr) have been conducted. Different concentrations of PEO
      solutions are injected to the polyethylene tubes by pressure, where they enter
      the capillary by EOF. Because the large DNA fragments migrate faster towards the
      cathode end under counterflow conditions, the introduction sequence is from low
      to high concentrations of PEO solutions after sample injection. Using the
      gradient CE approach, the separations of the DNA sample injected at 30 cm height
      for times up to 120 s have been demonstrated. The linearity between injection
      time and peak height shows that the DNA fragments stacked during migration from
      the sample zone to PEO. We found that stacking efficiency is greater when the
      analysis was performed by simultaneously changing the PEO and EtBr concentration,
      compared to individual changes in PEO concentration.

PMID- 14595681
TI  - Study of ethidium bromide effect on dsDNA separation by capillary zone
      electrophoresis and laser light scattering.
AB  - The effect of ethidium bromide (EB) on dsDNA separation was studied by using
      capillary zone electrophoresis (CZE) and laser light scattering (LLS). By
      increasing the concentration from 1 to 15 microg/mL, EB showed significant
      influence on the separation of pBR322 HaeIII in terms of resolution, speed, and
      signal-over-noise ratio. The physicochemical properties of DNA, such as mobility
      under electric field, charge-over-size ratio, and hydrodynamic radius, showed two
      declines, a sharp drop followed by a relaxed decrease, with increasing EB
      concentration. Such observations could be explained by using two modes of the dye
      binding process: intercalation and outside binding. The combination of results
      obtained from CZE and LLS also confirmed the existence of outside binding.
      Compared with intercalation, outside binding showed a weaker dye concentration
      dependence in neutralizing the negative charges on the DNA fragments. Static
      light scattering showed that <M(w)> and <R(g)> of DNA in 1xTris-borate-EDTA (TBE)
      were increased with increasing EB concentration. <R(g)>/<R(h)> of DNA with dye
      had a value larger than 1.5, suggesting a random coil conformation.

PMID- 14595682
TI  - Towards the development of an integrated capillary electrophoresis optical
      biosensor.
AB  - Extending the previous preliminary study on the construction of a capillary
      electrophoresis (CE)/sensor for the detection of reducing analytes, we focus the
      interest on the simultaneous detection of redox active species, which are
      important indicators of the oxidative damage in tissues, of food preservation,
      and of pollution. The CE/sensor was built by modifying the detector-portion of
      the capillary with the redox-sensitive polymer polyaniline (PANI). The analyte is
      detected by monitoring the changes in optical absorption of the PANI film. The
      CE/sensor was tested, with good results, with ascorbic acid, glutathione (GSH),
      as well as with compounds with very close similarity (ascorbic and isoascorbic
      acid). The kinetics of oxidation and reduction of PANI were evaluated. Further a
      PANI/CE-biological sensor was developed by coupling an enzyme, glucose oxidase
      (GOD), to the PANI-modified portion of the capillary. The stability of the
      immobilized GOD and the sensitivity of the CE/biosensor were studied, by using
      glucose as test analyte in concentrations within the physiological range. The
      results indicate that the CE/biosensor had good stability (more than 75% of
      original activity retained after 30 operational days), manufacturing
      reproducibility and a sensing range convenient for monitoring physiological
      glucose (1-24 mM).

PMID- 14595683
TI  - Capillary electrophoresis as a simple and sensitive method to study
      polysaccharides of Sinorhizobium sp. NGR234.
AB  - We report the minimum amounts of polysaccharides (6.5 ng) that can be studied
      using capillary electrophoresis-laser-induced fluorescence (CE-LIF) and describe
      the separation of the various monosaccharides susceptible to occur in
      Sinorhizobium cell wall. On-gel hydrolysis of the polysaccharides is described.
      It allowed the easy and rapid determination of the monosaccharide composition of
      the excised lipopolysaccharides. The composition obtained fits with gas
      chromatography-mass spectrometry (GC-MS) results. This study underlines the
      simplicity of using CE-LIF, which remains an entirely "water medium" method,
      unlike GC-MS which is, in addition, less sensitive (at least 100-fold) than CE
      LIF.

PMID- 14595684
TI  - High-resolution single-stranded DNA analysis on 4.5 cm plastic electrophoretic
      microchannels.
AB  - Plastic microchannels (4.5 cm long) fabricated from an etched glass master were
      tested for high-resolution single-stranded DNA analysis. Using replaceable
      denaturing linear polyacrylamide as sieving matrix, one-color separation of a
      fragment sizing standard with single-base resolution (R > 0.5) was achieved up to
      275 bases. Two-color sizing analysis of four loci short tandem repeat (STR)
      allelic ladder (CSF1PO, TPOX, TH01, vWA) with single-base resolution (R = 0.62)
      on TH01 alleles 9.3 (198 bp) and 10 (199 bp) was demonstrated. An average
      standard deviation of +/- 0.06 bp and +/-0.11 bp in sizing 32 alleles of the CTTv
      ladder was attained between runs and between channels, respectively. Four-color
      sequencing separation of a terminator sequencing standard showed a base-calling
      accuracy of 99.1% out to 320 bases in 13 min.

PMID- 14595685
TI  - Rice proteomics: current status and future perspectives.
AB  - Rice, the first cereal crop genome to be decoded, has attracted the attention of
      researchers worldwide because of its immense socio-economic impact on human
      existence. With the availability of the draft genome sequence of two major types,
      japonica- and indica-rice, "rice proteomics" has entered into the era of
      functional genomics. Although during the last decade an important but limited
      progress (mainly construction of protein datafiles) has been made in the field of
      rice proteomics, it is only recently that dedicated research groups have taken
      this challenge to systematically analyze the rice proteome at the cell (and
      organelle), tissue, and whole plant level. Important gains achieved by the
      accelerated technological progress in protein separation and identification will
      help in going beyond the simple cataloguing of rice proteins in realistic terms.
      In this review, we discuss the progress made in the field of rice proteomics to
      date and dwell upon the future direction/problems/approaches towards defining the
      rice proteome.

PMID- 14595686
TI  - Quantitative evaluation of sample application methods for semipreparative
      separations of basic proteins by two-dimensional gel electrophoresis.
AB  - The use of cup-loading for sample application has become widely used in two
      dimensional electrophoresis (2-DE) for resolution of basic proteins, but no side
      by-side quantitative study has been published which compares cup-loading with the
      alternative passive and active rehydration methods to fully promote one type of
      loading method over another. Replicate 2-D gels from each loading method were
      quantitatively evaluated for gel-to-gel reproducibility using IPG 6-11 strips and
      semipreparative protein loads (300 microg). Gels were stained with SYPRO Ruby and
      analyzed with PDQuest. An inexpensive home-made assembly for cup-loading was used
      with the Protean IEF Cell for separation of whole cell extracts from the
      archaeon, Sulfolobus solfataricus. Cup-loading was determined to be far superior
      for IPG 6-11 separations than active or passive rehydration methods. Cup-loading
      consistently produced the greatest number of detectable spots, the best spot
      matching efficiency (56%), lowest spot quantity variations (28% coefficient of
      variation, CV), and the best-looking gels qualitatively. The least satisfactory
      results were obtained with active rehydration, followed closely by passive
      rehydration in off-line tubes. Passive rehydration experiments, performed using
      an on-line isoelectric focusing (IEF) tray, produced comparable spot numbers to
      cup-loading (84%), with 55% of the spots having higher intensity but 10% more
      spot quantity variance than cup-loading.

PMID- 14595687
TI  - Comparative proteome analysis of culture supernatant proteins from virulent
      Mycobacterium tuberculosis H37Rv and attenuated M. bovis BCG Copenhagen.
AB  - A comprehensive analysis of culture supernatant (CSN) proteins of Mycobacterium
      tuberculosis H37Rv was accomplished by combination of two-dimensional
      electrophoresis (2-DE), mass spectrometry, and N-terminal sequencing by Edman
      degradation. Analytical 2-DE gels resolved approximately 1250 protein spots from
      CSN of M. tuberculosis H37Rv, 381 of which were identified by mass spectrometry
      and/or Edman degradation. This study revealed 137 different proteins, 42 of which
      had previously been described as secreted. Comparative proteome analysis of CSN
      from virulent M. tuberculosis H37Rv and attenuated Mycobacterium bovis BCG
      Copenhagen identified 39 M. tuberculosis-specific spots containing 27 different
      proteins, representing candidate antigens for novel vaccines and diagnostics in
      tuberculosis. These included five proteins encoded by open reading frames absent
      from M. bovis BCG, e.g., early secretory antigen target (Esat6), as well as 22
      novel differential proteins, such as acetyl-CoA C-acetyltransferase (Rv0243) and
      two putative Esat6-like proteins (Rv1198, Rv1793).

PMID- 14595689
TI  - Proteome database of unsensitized CD4 positive T lymphocytes in T cell receptor
      transgenic mice.
AB  - We established a two-dimensional electrophoresis (2-DE) mapping database of
      splenic CD4 T cells prepared from I-A(d)-restricted ovalbumin (OVA)(323-339)
      specific T cell receptor (TCR) transgenic mice (OVA23-3). First we examined the
      purification of CD4 T cells and found that the high purity of cells produced more
      accurate protein maps. The first dimension utilized narrow-range immobilized pH
      gradients (IPGs), pH 4.0-5.0, pH 4.5-5.5, pH 5.0-6.0, and pH 5.5-6.7.
      Approximately 1300 spots were detected by silver staining. Detection was
      performed by in-gel tryptic digestion of the spots, matrix assisted laser
      desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS) technology
      and database searches via the world wide web (WWW). We have so far identified 255
      proteins on 2-DE gels of whole cell lysates. This is the first construction of a
      proteome database for murine unsensitized CD4 T lymphocytes. To examine this
      further, 2-DE mapping was utilized for splenic CD4 T cells from another TCR
      transgenic mouse strain (DO11.10 TCR transgenic mice). Mapping patterns were
      found to be almost identical to those from CD4 T cells from OVA23-3 mice. These
      results indicated that the 2-DE maps in this study could be used for mouse CD4 T
      cells to examine protein changes in cells given certain stimuli.

PMID- 14595688
TI  - Proteomics of loosely bound cell wall proteins of Arabidopsis thaliana cell
      suspension cultures: a critical analysis.
AB  - The complete sequencing of the Arabidopsis thaliana genome allows the use of the
      recently developed mass spectrometry techniques to identify the cell wall
      proteins (CWPs). Most proteomic approaches depend on the quality of sample
      preparation. Extraction of CWPs is particularly complex since the proteins may be
      free in the apoplast or are embedded in a polysaccharide matrix where they are
      retained by Van der Waals interactions, hydrogen bonds, hydrophobic or ionic
      interactions, or cross-linked by covalent bonds. Specific and sequential
      extraction procedures thus need to be developed. We report on the sequential
      extraction of loosely bound CWPs from living A. thaliana cells in culture.
      Different salts and chelating agents were used for releasing the proteins from
      the wall. Their effects on the extraction of CWPs and on the integrity of the
      plasma membrane were evaluated. Bioinformatic software was used to identify
      proteins and to predict their sub-cellular localization. The obtained data show
      that the plasma membrane of cells in culture was easily damaged by some steps of
      the extraction procedure, leading to the release of increasing amounts of
      intracellular proteins. Nevertheless, we identified fifty CWPs among which
      thirteen were new proteins for the cell wall. In addition, 76% of these CWPs were
      basic proteins not resolved in two-dimensional (2-D) gel electrophoresis. The
      existence of two hypothetical proteins was confirmed. The structure of three
      proteins could be confirmed using mass spectrometry data.

PMID- 14595690
TI  - Proteomic analysis of the tumorigenic human prostate cell line M12 after
      microcell-mediated transfer of chromosome 19 demonstrates reduction of vimentin.
AB  - Critical alterations in proteins that accompany or control the aggressiveness of
      human prostate cancers remain poorly defined. Previously we demonstrated that the
      highly tumorigenic, metastatic human prostate cell line M12 was converted to a
      slow growing, poorly tumorigenic cell line by introduction of an intact human
      chromosome 19, generating the M12 (F6) hybrid cells. The objective of this report
      was to identify changes in the protein profile of these M12(F6) microcell hybrid
      cells. A combination of two-dimensional gel electrophoresis and matrix assisted
      laser desorption-time of flight-mass spectroscopy was used to compare proteins
      made by these two cell lines. No consistently increased proteins were identified.
      However, seven proteins were reproducibly reduced more than twofold: vimentin,
      hsp90, ATP synthase, 26S protease regulatory subunit, heterogeneous nuclear
      ribonucleoprotein, T-Complex protein 1 beta, and alpha-1 tubulin. The striking
      reduction in vimentin protein was accompanied by significantly decreased vimentin
      mRNA, revealed by Northern blotting. Our findings implicate reduced vimentin in
      the conversion of these tumorigenic prostate epithelial cells into slow growing,
      less aggressive cells. These studies demonstrate that application of proteomic
      analysis to specific problems in an experimental context can yield biologically
      relevant information about the prostate cancer cell phenotype.

PMID- 14595691
TI  - 19th American Electrophoresis Society Conference 2002: focus on interdisciplinary
      science.

PMID- 14595692
TI  - Avoiding pitfalls in electrokinetic remediation: robust design and operation
      criteria based on first principles for maximizing performance in a rectangular
      geometry.
AB  - The role of the symmetrical conditions on the temperature field is studied in a
      capillary of rectangular geometry. By using the generalized flux, i.e., Robin
      type of boundary conditions for the heat transfer in such a capillary domain, it
      is possible to identify clearly conditions under which the velocity field will
      depend crucially on the basic parameters and, therefore, what types of flow
      regimes may arise in the capillary channel. In addition, it is possible to
      conclude under what conditions the velocity field will not at all depend on some
      of these. The behavior is intimately tied to the symmetrical conditions
      associated with the temperature field in the system. A "skew" or asymmetrical
      parameter, W infinity, has been identified in the temperature profiles; this
      parameter is useful for studying the role of the symmetrical conditions on the
      hydrodynamics field and in determining a set of a priori design criteria that
      limits the range of values of the parameters. Several numerical examples are
      presented to show the flow situations found in the system.

PMID- 14595693
TI  - Sequence-dependent bending in plasmid pUC19.
AB  - The circular permutation assay has been used to characterize sequence-dependent
      bending in plasmid pUC19 (2686 bp). Linear, permuted sequence isomers of pUC19
      exhibit different mobilities in large-pore polyacrylamide gels, suggesting that
      the plasmid contains two sequence-dependent bends, one located at approximately
      806 bp, close to the start site of transcription, and the other at approximately
      2617 bp, near the promoter of the ampicillin resistance gene. The mobility
      patterns are independent of the buffer in which the gels are cast and run,
      independent of pH over the range 6.5-8.6, and independent of the presence or
      absence of various monovalent ions added to the buffer, suggesting that the
      maxima in the mobility patterns correspond to stable bends in the helix backbone,
      not anisometric flexibility. Although the mobility patterns are unchanged when
      Ba(++) or Zn(++) ions are added to the buffer, several of the sequence isomers
      exhibit multiple sharp sub-bands in solutions containing Mg(++) or Ca(++) ions,
      indicating the presence of multiple conformational isomers. In addition, the
      mobility maximum near the start site of transcription is shifted by approximately
      100 bp in the presence of Ca(++) ions, suggesting that the location of the actual
      bend center is somewhat variable, depending on the ionic composition of the
      surrounding medium. The number of maxima observed in the mobility pattern can be
      increased by adding a bend from another plasmid, such as Litmus 28; the number of
      maxima can be decreased by removing one of the bends in pUC19 by restriction
      enzyme digestion and religation. Hence, the number of maxima in the mobility
      pattern is an accurate indication of the number of stable, sequence-dependent
      bends present in the plasmid. The combined results indicate that the circular
      permutation assay in large-pore polyacrylamide gels is a reliable method of
      detecting and analyzing sequence-dependent bends in kilobase-sized DNA molecules.

PMID- 14595694
TI  - Thousandfold signal increase using field-amplified sample stacking for on-chip
      electrophoresis.
AB  - Field-amplified sample stacking (FASS) leverages conductivity gradients between a
      volume of injected sample and the background buffer to increase sample
      concentration. A major challenge in applying FASS to on-chip assays is the
      initial setup of high-conductivity gradient boundaries in the region of the
      injected sample volume. We have designed, fabricated, and characterized a novel
      FASS-capillary electrophoresis (CE) chip design that uses a photoinitiated porous
      polymer structure to facilitate sample injection and flow control for high
      gradient FASS. This polymer structure provides a region of high flow resistance
      that allows the electromigration of sample ions. We have demonstrated an
      electropherogram signal increase by a factor of 1100 in electrophoretic
      separations of fluorescein and Bodipy with, respectively, 2 microM and 1 microM
      initial concentrations.

PMID- 14595695
TI  - Impact of prefractionation using Gradiflow on two-dimensional gel electrophoresis
      and protein identification by matrix assisted laser desorption/ionization-time of
      flight-mass spectrometry.
AB  - Prefractionation of protein samples prior to two-dimensional electrophoresis (2
      DE) has the potential to increase the dynamic detection range for proteomic
      analysis. We evaluated a membrane-based electrophoretic separation technique
      (Gradiflow) for its ability to fractionate an exoproteome sample from the
      filamentous fungus Trichoderma reesei. The sample was separated on the basis of
      size and charge. Buffer optimization was found to be necessary for successful
      size fractionation. Fractionation by charge was used to resolve the sample into
      four fractions that were subjected to analysis by two-dimensional electrophoresis
      (2-DE). Enhanced detection of low-abundance proteins with selective removal of
      high-abundance species was achieved. Fractionated and unfractionated samples were
      examined for differences in the ability to identify proteins following 2-DE using
      trypsin in-gel digestion followed by peptide mass fingerprinting using matrix
      assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF
      MS). Fractionated samples showed marked improvement in protein identification
      ability and sequence coverage. This study demonstrates the utility of the
      Gradiflow for fractionation, resulting in an enhancement of resolution and
      characterization of a moderately complex proteome.

PMID- 14595697
TI  - Quantitative and qualitative measure of intralaboratory two-dimensional protein
      gel reproducibility and the effects of sample preparation, sample load, and image
      analysis.
AB  - We investigate one approach to assess the quantitative variability in two
      dimensional gel electrophoresis (2-DE) separations based on gel-to-gel
      variability, sample preparation variability, sample load differences, and the
      effect of automation on image analysis. We observe that 95% of spots present in
      three out of four replicate gels exhibit less than a 0.52 coefficient of
      variation (CV) in fluorescent stain intensity (% volume) for a single sample run
      on multiple gels. When four parallel sample preparations are performed, this
      value increases to 0.57. We do not observe any significant change in quantitative
      value for an increase or decrease in sample load of 30% when using appropriate
      image analysis variables. Increasing use of automation, while necessary in modern
      2-DE experiments, does change the observed level of quantitative and qualitative
      variability among replicate gels. The number of spots that change qualitatively
      for a single sample run in parallel varies from a CV = 0.03 for fully manual
      analysis to CV = 0.20 for a fully automated analysis. We present a systematic
      method by which a single laboratory can measure gel-to-gel variability using only
      three gel runs.

PMID- 14595696
TI  - Proteomic analysis of transducin beta-subunit structural heterogeneity.
AB  - Partially purified transducin was resolved using two-dimensional gel
      electrophoresis (2-DE). Peptide mass fingerprinting of several different spots
      believed to correspond to the 37 kDa beta-subunit of transducin (T(beta)) was
      performed. Spots were excised and proteolyzed using modified trypsin. Matrix
      assisted laser desorption/ionization-mass spectrometry (MALDI-MS) was performed
      on the peptide mixture resulting from each spot. As many as six spots with
      different pI, ranging from 5.2 to 6.1, were observed when separated using 2-DE.
      MALDI peptide mass fingerprinting determined with high probability that all of
      the spots were the same gene product, guanine nucleotide-binding protein
      G(I)/G(S)/G(T) beta-subunit 1 (GNB1; T(beta1)). This suggested that post
      translational modification was responsible for the differences in pI.
      Phosphorylation experiments showed that at least one T(beta1) spot was
      phosphorylated in vitro with [gamma-(32)P]ATP by an endogenous kinase. Treatment
      of T(beta) with alkaline phosphatase caused a large change in the spot pattern of
      T(beta), suggesting that phosphorylated T(beta) is a substrate for alkaline
      phosphatase. We conclude that T(beta1) constitutes over 99% of the T(beta)
      expressed in bovine rod outer segments and displays structural heterogeneity that
      is due to post-translational modification. We also conclude that some, but not
      all, of the heterogeneity observed is due to phosphorylation of Tb1.

PMID- 14595698
TI  - Comparison of automated in-gel digest methods for femtomole level samples.
AB  - A comparison of automated in-gel digestion methods for low picomolar to
      femtomolar levels of protein is presented. Gel spots with 4 pmol to 120 fmol of
      protein were stained with either Coomassie colloidal blue or SYPRO Ruby and
      digested using an automated platform. The sequence coverages and average peak
      intensities obtained from a matrix-assisted laser desorption/ionization-mass
      spectrometry (MALDI-MS) analysis are compared. Results show that methods using an
      acetonitrile extraction or digest times greater than the standard 4 h give no
      significant increase in peptide sequence coverage for automated digestion of low
      protein level samples. It is also shown that digests from SYPRO Ruby-stained gels
      show a greater improvement upon ZipTip cleanup than digests from Coomassie
      colloidal blue-stained gels. The digests from SYPRO Ruby-stained gels are also
      shown to give a higher average peptide intensity if a method with minimal gel
      plug washing is used.

PMID- 14595701
TI  - Mometasone furoate degradation and metabolism in human biological fluids and
      tissues.
AB  - The in vitro metabolic and non-metabolic degradation kinetics of mometasone
      furoate (MF) was investigated in selected human biological fluids and subcellular
      fractions of tissues. Qualitative and quantitative differences in transformation
      profiles of MF were observed among human biological media. Degradation was the
      major event in plasma and urine with four new degradation products identified; A:
      21-chloro-17alpha-hydroxy-16alpha-methyl-9beta,11beta-oxidopregna-1,4-diene-3,20
      dione 17-(2-furoate), B: 9alpha,21beta-dichloro-11beta,21alpha-dihydroxy-16alpha
      methylpregna-1,4,17,20-tetraen-3-one 21-(2-furoate), C: 21beta-chloro-21alpha
      hydroxy-16alpha-methyl-9beta,11beta-oxidopregna-1,4,17,20-tetraen-3-one 21-(2
      furoate), and D: 21-chloro-17alpha-hydroxy-16alpha-methyl-9beta,11beta
      oxidopregna-1,4-diene-3,20-dione. A, B and C were predominant and D was minor in
      plasma while A and C were predominant in urine. Hydrolysis of the 17-ester bond
      of MF was not a major event in plasma. The turnover of MF in plasma was faster
      than that in phosphate buffers of pH 7.4. Metabolism of MF occurred primarily and
      rapidly in liver, appreciably in intestine, but negligibly in in vitro lung
      tissue. While 6beta-hydroxylation was a major metabolic pathway for MF in
      microsomes of both human liver and intestine, other parallel and subsequent
      metabolism pathways could also be involved. If these degradation and metabolic
      products are also formed and active in humans in vivo, both MF and its 'active'
      products need to be taken into account when determining the systemic
      bioavailability of MF and in establishing concentration-effect relationships with
      this drug.

PMID- 14595702
TI  - Pharmacokinetic characterization of a human immunodeficiency virus protease
      inhibitor, saquinavir, during ethanol intake in rats.
AB  - Throughout therapeutic drug monitoring of human immunodeficiency virus (HIV)
      protease inhibitors in HIV-infected patients, it was found that plasma
      concentrations of saquinavir (SQV) were reduced in patients who had a habit of
      alcohol intake during double protease therapy with SQV and ritonavir (RTV). This
      study confirmed the pharmacokinetic profiles of SQV during ethanol intake in
      rats. After oral administration of SQV alone (20 mg/kg) in rats prepared by free
      access to 15% ethanol solution for 14 days (day 14 rats), the area under the
      concentration vs time curves (AUC) showed a significant decrease (p<0.01) in
      comparison with control rats from 0.78+/-0.10 to 0.38+/-0.03 microg h/ml. For
      intravenous administration of SQV alone (5 mg/kg) to day 14 rats, the total body
      clearance increased significantly by 1.4-fold (p<0.05), whereas for intracolonic
      administration of SQV alone, no significant differences in the values of
      pharmacokinetic parameters were found between control and day 14 rats. With RTV,
      which has the strongest inhibitory effect on the CYP3A enzyme of the current HIV
      protease inhibitors, the AUC values of SQV at RTV doses of 2 and 20 mg/kg in day
      14 rats also decreased significantly (p<0.01) from 1.30+/-0.06 to 0.57+/-0.05
      microg h/ml and from 17.63+/-1.66 to 4.18+/-0.94 microg h/ml, respectively,
      indicating that the degree of the decrease of AUC values after oral
      administration with RTV after ethanol intake was larger than the mono-therapy
      with SQV. This study showed that ethanol-intake decreases the bioavailability of
      SQV after oral administration alone or with RTV. These observations provide
      useful information for the treatment of HIV-infected patients when they receive a
      combination therapy with SQV and RTV, and arouse attention for the effects of
      alcohol intake.

PMID- 14595703
TI  - Pharmacokinetics and tissue distribution of uraemic indoxyl sulphate in rats.
AB  - The purpose of the present study was to examine the pharmacokinetic properties of
      indoxyl sulphate, a harmful uraemic toxin that accumulates during chronic renal
      failure. The pharmacokinetics and tissue distribution of indoxyl sulphate were
      examined in normal and 5/6 nephrectomized (CRF) rats. The uptake process of
      indoxyl sulphate by rat renal cortical slices in vitro was also investigated.
      Endogenous indoxyl sulphate was found to be mainly distributed in the kidney. The
      rate of elimination of indoxyl sulphate from plasma was lower in CRF rats
      compared with sham-operated rats. The majority of intact indoxyl sulphate was
      excreted in the urine. In renal cortical slice experiments, uptake of indoxyl
      sulphate was a saturable process with a K(m) of 43.0 microm. Furthermore,
      sulphate conjugates, such as oestrone sulphate and dehydroepiandrosterone
      sulphate, inhibited the uptake of indoxyl sulphate to a greater extent than PAH.
      Thus, indoxyl sulphate is primarily eliminated from the plasma via the kidney by
      active tubular secretion, and renal uptake of indoxyl sulphate appears to be
      mediated by an organic anion transport system with a high affinity for oestrone
      sulphate and dehydroepiandrosterone sulphate.

PMID- 14595704
TI  - Acetyl-L-carnitine permeability across the blood-brain barrier and involvement of
      carnitine transporter OCTN2.
AB  - OCTN2 (SLC22A5), an organic cation/carnitine transporter, is widely distributed
      throughout the body, including the brain. In the present study, the involvement
      of OCTN2 in acetyl-L-carnitine (ALCAR) permeation across the blood-brain barrier
      (BBB) was examined using a microdialysis method in mouse. OCTN2 function was
      examined by comparison of wild-type mice with jvs mice, which express defective
      OCTN2 and are considered a model for primary systemic carnitine deficiency. Zero
      net-flux method analysis indicated higher in vivo recovery of ALCAR and lower
      physiological ALCAR concentration in thalamus extracellular fluid (ECF) in jvs
      mice compared with wild-type mice. Externally added ALCAR showed significantly
      slower initial uptake across the BBB in jvs mouse. These results indicated that
      OCTN2 is functionally involved in ALCAR transfer across the BBB. Total
      radioactivity in ECF after i.v. administration of radiolabelled ALCAR remained
      constant for the rest of the experimental period. Accordingly, our results
      indicate that ALCAR is transported from blood to brain ECF by OCTN2 at least in
      part, and its concentration in brain ECF is regulated by other events such as
      protein binding and anabolic reactions in the brain, as well as by transport
      across the BBB.

PMID- 14595706
TI  - Langerhans cell histiocytosis patients have HLA Cw7 and DR4 types associated with
      specific clinical presentations and no increased frequency in polymorphisms of
      the tumor necrosis factor alpha promoter.
AB  - BACKGROUND: Current theory on the etiology of Langerhans cell histiocytosis
      (LCH), formerly Histiocytosis-X, is that abnormality(ies) of the immune system
      are responsible for dysregulation of Langerhans cells (LC) in patients' lesions.
      Among the known abnormalities in LCH patients are increased amounts of tumor
      necrosis factor alpha (TNF-alpha) and other cytokines in the lesions. PROCEDURE:
      We investigated the human leukocyte antigen (HLA) phenotypes of 29 patients and
      37 healthy family members to determine if any haplotypes segregate with the
      presence or locations of the disease. The lymphocyte subsets for 22 patients and
      11 family members were also determined. RESULTS: Patients with single bone,
      multiple bone, or multi-system LCH had different relative proportions of HLA
      types. Patients presenting with single bone disease had an especially high
      frequency of the DR4 type. In this patient group, every Caucasian patient had
      either Cw7 or DR4. Lymphopenia was documented in patients who had been off
      therapy as well as those who only had surgical curetage of their lesions. Family
      members also had low numbers of T lymphocytes. There were fewer mutations of the
      TNF-alpha promoter in patients than in the general population. CONCLUSIONS:
      Although there is an increased percentage of LCH patients with DR4 and/or Cw7
      there was also an increased prevalence of this antigen as well as lymphopenia
      among unaffected family members. Additional genetic and/or environmental factors
      are necessary to explain this association. TNF-alpha promoter mutations are not
      responsible for the increased production of this cytokine.

PMID- 14595707
TI  - Neuroblastoma in adolescents and adults: the Memorial Sloan-Kettering experience.
AB  - BACKGROUND: We reviewed the utility of different treatment modalities in a large
      series of adolescents/adults with neuroblastoma (NB). PROCEDURE: The 30
      adolescents/adults (median age, 19 years) had stage 2B (n = 1), 3 (n = 2), or 4
      (n = 27) NB. Treatments included conventional and myeloablative therapy; local
      radiotherapy (RT); immunotherapy with anti-G(D2) 3F8 monoclonal antibody +/-
      granulocyte-macrophage colony-stimulating factor (GM-CSF); and 3F8 alternating
      with low-dose oral etoposide. RESULTS: Seven patients are in first (n = 4) or
      second (n = 3) complete/very good partial remission (CR/VGPR) at 9+ to 181+
      (median, 45+) months. Among 13 newly diagnosed or minimally prior-treated
      patients, no major responses were seen in 4/4 treated with N4/N5 chemotherapy,
      but 6/9 treated with the higher dose N6/N7 regimens and surgery had major
      responses, and immunotherapy produced CR in BM in three patients. Among 17
      patients referred because of resistant NB, favorable responses occurred in 6/12
      treated with high-dose cyclophosphamide-based salvage therapy, including one
      patient who is in CR 170+ months after myeloablative consolidation and five
      patients who achieved CR/VGPR after 3F8/GM-CSF (n = 4) or 3F8/oral etoposide (n =
      1). With a median follow-up of 32+ months post-RT, no local relapses occurred in
      10/10 patients who received hyperfractionated 21 Gy RT to prevent regrowth of
      soft tissue masses that had been resected. CONCLUSIONS: High-dose chemotherapy
      and surgery can achieve a minimal disease state in >50% of newly diagnosed older
      NB patients. In that setting, local RT, and the use of agents with recently
      confirmed anti-NB activity, including anti-G(D2) antibodies, and cis-retinoic
      acid, may improve the poor prognosis of these patients reported to date.

PMID- 14595708
TI  - Differences in vasculature between pilocytic and anaplastic astrocytomas of
      childhood.
AB  - BACKGROUND: The clinical manifestations of childhood pilocytic astrocytoma (PA)
      and anaplastic astrocytoma (AA) markedly differ, especially in the time to
      progression and prognosis. Because of the aggressive course and poor survival
      rate of AA, one would expect it to be associated with a high angiogenic index.
      Counterintuitively, we often find higher microvessel density counts in PA than in
      AA. PROCEDURE: We examined the differences in type or density of microvasculature
      between the two neoplasms. To differentiate established, mature vessels from
      immature growing ones, we used antibodies to Factor VIII (FVIII) to stain
      endothelial cells (ECs) of blood vessels and alpha-smooth muscle actin (alpha
      SMA) antibodies to stain vessels supported by adventitia. RESULTS: We found that
      large, mature, alpha-SMA-positive vessels predominated in PA, and small,
      immature, alpha-SMA-negative vessels in AA. The vessel maturation index was 54.5%
      for PA, and 6.1% for AA. Immunostaining with vascular endothelial growth factor
      (VEGF) and anti-flt-1/VEGF receptor-1 antibodies showed distinct tissue patterns.
      VEGF immunoreactivity occurred mainly in the processes of the tumor astrocytes in
      PA; the opposite was observed in AA. flt-1/VEGFR-1 was detected in the tumor
      cells of AA but not in those of PA. CONCLUSIONS: We propose that the predominance
      of small, alpha-SMA-negative vessels in AA represents immature, unstable
      vasculature with a potentially greater susceptibility to anti-angiogenic therapy.
      The expression of both flt-1 and VEGF by AA tumor cells also suggests a possible
      autocrine growth-promoting function for VEGF in addition to its role as paracrine
      pro-angiogenic growth factor for activated ECs, thus making anti-angiogenesis an
      attractive therapeutic target in the treatment of AA.

PMID- 14595710
TI  - Malawi pilot study of Burkitt lymphoma treatment.
AB  - BACKGROUND: Burkitt lymphoma (BL) accounts for 50% of childhood cancer in Malawi.
      Lack of resources precludes the use of new successful treatment approaches such
      as the LMB 89 group B protocol, which cures >80% of children with stage III BL
      with high dose chemotherapy and matching supportive care. Our objective was to
      achieve a good cure rate in Murphy stage I-III BL with manageable toxicity in
      Malawi at a drug cost of <1000 US dollars per patient. PROCEDURE: The intensity
      and toxicity of the LMB 89 group B protocol was reduced and adapted to Malawi
      realities. All stages received the same treatment. Children with suspected BL in
      the period July 1997-November 1999 were subjected to abdominal ultrasound, a
      tumor biopsy and/or fine needle aspirate (FNA) and bone marrow (BM),
      cerebrospinal fluid (CSF), and peripheral blood examination. HIV seropositive
      children were excluded. Endpoints are projected event free survival (EFS) at
      minimum 1 year, blood and gastro-intestinal tract toxicity, and risk for and
      severity of infections. RESULTS: Forty-four children were eligible for treatment
      and analysis. Their median age was 7.2 years, M:F ratio 1.4:1 with 10 stage I, 5
      stage II, and 29 stage III patients. Projected Kaplan-Meier EFS for all was 57%
      (CI 41-73) at 1 year with 90% EFS in stage I and 52% EFS in stage III. The
      survival curve remained stable at 500 days. Toxicity and delays in appropriate
      supportive care contributed to ten deaths during treatment. Local recurrent tumor
      caused five and CNS recurrence one death. Two children died from progressive
      disease. The incidence of severe (grade 3 and/or 4) hematologic toxicity varied
      from 13% to 36%, gastro-intestinal toxicity (GIT) from 2% to 17%, and infections
      from 7% to 41% per chemotherapy module. CONCLUSIONS: It is possible to administer
      less intense and less costly multiagent chemotherapy to children with BL in a
      developing society with acceptable EFS rates. Adequate supportive care of the at
      times associated severe toxicity must be made available to better the results.

PMID- 14595709
TI  - Epigenetic changes in the DAP-kinase CpG island in pediatric lymphoma.
AB  - BACKGROUND: Hypermethylation of CpG islands in the promoter region of death
      associated protein kinase (DAP-kinase) coupled with the loss of gamma-interferon
      induced apoptosis have been reported in B-cell malignancies suggesting a role in
      pathogenesis or prognosis. Along with B-cell malignancies, pediatric lymphomas
      also include T-cell non-Hodgkin lymphoma (NHL), anaplastic large cell lymphoma,
      and Hodgkin disease, each with unique prognoses. The purpose of this study was to
      elucidate epigenetic changes in the DAP-kinase promoter region of pediatric cases
      to determine associations with aberrant hypermethylation. PROCEDURES: Thirty-nine
      cases of different lymphoid pathology [10 Burkitt lymphoma, 1 B-cell NHL; 7 T
      cell lymphoblastic lymphoma; 4 anaplastic large cell lymphoma (LCL); 2 B-cell
      LCL; 14 nodular sclerosing Hodgkin disease (NSHD); and 1 B-cell acute
      lymphoblastic leukemia (ALL)] had methylation-specific polymerase chain reaction
      performed on bisulfite-treated DNA, which distinguishes the methylation status of
      the promoter region, and DAP-kinase mRNA expression assays performed on available
      specimens. RESULTS: In normal lymphocytes, the CpG islands in the promoter region
      were unmethylated, as were the T-cell lymphoblastic lymphoma and anaplastic LCL.
      In contrast, 100% of the Burkitt lymphoma (10/10) and B-cell ALL (1/1) were
      hypermethylated. Of the specimens with mRNA available, 7/8 Burkitt lymphoma had
      no DAP-kinase mRNA expression compared to normal expression in 3/3 and 4/4 T-cell
      lymphoblastic lymphoma and NSHD, respectively. CONCLUSIONS: In these pediatric
      lymphoid tumors, hypermethylation of the DAP-kinase promoter region with
      associated loss of DAP-kinase gene expression was associated with B-cell
      malignancies and thus may be important in the development and/or provide a
      prognostic tool in B- cell lymphomas.

PMID- 14595711
TI  - 14th EORTC-NCI-AACR symposium on "Molecular Targets and Cancer Therapeutics,"
      November 19-22, 2002, Frankfurt, Germany.

PMID- 14595712
TI  - Pre- or post-operative treatment for Wilms tumor? Who, what, when, where, how,
      why--and which.

PMID- 14595713
TI  - Infantile choriocarcinoma treated with chemotherapy alone.

PMID- 14595714
TI  - Long-term remission after non-radical surgery combined with brachytherapy in an
      infant with a chemo-resistant rhabdomyosarcoma of the tongue.

PMID- 14595715
TI  - Brachytherapy in pediatric oncology.

PMID- 14595716
TI  - Response to low dose temozolomide in radiation induced gliomatosis cerebri.

PMID- 14595717
TI  - Patterns of failure after induction chemotherapy followed by consolidative
      radiation therapy for children with central nervous system germinoma.

PMID- 14595718
TI  - Radiographic response at end of therapy with carboplatin and vincristine as a
      prognostic indicator in children with low-grade astrocytoma.

PMID- 14595720
TI  - Brain metastases in children with neuroblastoma--a single-institution experience.

PMID- 14595719
TI  - Neurofibromatosis type 1 and multiple primary malignancies.

PMID- 14595721
TI  - Identification of two distinct subpopulations in a ganglioneuroblastoma: lack of
      co-localization of vasoactive intestinal polypeptide and calcitonin in ganglionic
      cells at the ultrastructural level.

PMID- 14595723
TI  - Erdheim-Chester disease in a child.

PMID- 14595722
TI  - Wilms tumor and cardiomyopathy.

PMID- 14595724
TI  - Bone mass and bone mineral metabolism at diagnosis and after intensive treatment
      in children with acute lymphoblastic leukemia.

PMID- 14595725
TI  - Chronic papilloedema due to intra-orbital Langerhans cell histiocytosis.

PMID- 14595726
TI  - Local control in childhood extremity sarcomas: salvaging limbs and sparing
      function.

PMID- 14595727
TI  - Surviving childhood cancer: what next? Issues under consideration at the After
      Completion of Therapy (ACT) clinic in India.

PMID- 14595728
TI  - High incidence of brain tumors of childhood in Hungary between 1989 and 2001.

PMID- 14595729
TI  - Tumor lysis syndrome and neuroblastoma.

PMID- 14595730
TI  - Importance of informed consent in offering to return research results to research
      participants.

PMID- 14595731
TI  - Kaposiform hemangioendothelioma and therapy with interferon-alpha.

PMID- 14595733
TI  - Flash-echo gray-scale imaging in the subtraction mode for assessing perfusion of
      small hepatocellular carcinoma.
AB  - PURPOSE: The aim of this study was to evaluate the effectiveness of using flash
      echo imaging (FEI) in the subtraction mode to assess the vascularity of small
      hepatocellular carcinomas (HCCs) that had been unsatisfactorily assessed with
      power Doppler sonography. METHODS: Between May 2000 and April 2001, we
      prospectively assessed nodular small HCCs using FEI in the subtraction mode after
      power Doppler sonography resulted in unsatisfactory images. After microbubble
      contrast was injected, we used the FEI technique to assess tumor perfusion in the
      arterial, portal, and delayed phases. RESULTS: Our study population comprised 14
      patients (10 men and 4 women) whose ages ranged from 31 to 79 years (mean, 61 +/-
      13.7 years) and whose tumors ranged in size from 0.8 to 3 cm (mean, 1.8 +/- 0.5
      cm). Power Doppler sonography was unable to assess tumor vascularity in 6 cases
      because of interference by heart pulsation, and it failed to detect a color
      signal in the other 8 cases. All tumors were enhanced with FEI. In the arterial
      phase, 7 of the 14 tumors (50%) showed hyperperfusion relative to liver
      parenchyma enhancement, 5 of 14 (36%) showed isoperfusion, and 2 of 14 (14%)
      showed hypoperfusion. In the portal phase, 3 of the 14 tumors (21%) showed
      isoperfusion, and the other 11 (79%) showed hypoperfusion. In the delayed phase,
      all 14 tumors showed hypoperfusion. CONCLUSIONS: Despite heart pulsation and slow
      vascular flow, FEI in the subtraction mode was sensitive and effective in
      assessing the perfusion of small HCCs.

PMID- 14595734
TI  - Sonographic measurement of calcaneal volume for determination of skeletal age in
      children.
AB  - PURPOSE: The purposes of this study were first to prospectively evaluate the
      feasibility of using sonographic measurements of volume of the ossified part of
      the calcaneus to determine skeletal age in healthy children and second, to
      provide normal ranges of this volume by sex and age up to 6 years. METHODS: Four
      hundred normal girls and boys ranging in age from 1 day to 6 years were examined
      sonographically to determine the volume of the calcaneal ossification center. The
      children were randomly divided into 2 groups. The first group (300 children) was
      used to determine normal values for the mean calcaneal volume by age and sex. The
      second group (100 children) was used to validate those normal values. RESULTS:
      The sonographically determined volume of the calcaneal ossification center
      correlated well with the chronologic age of the children. The calcaneal
      ossification centers of boys were larger than those of girls within the same age
      groups from ages 2 to 10 months, but from 11 months to 6 years old, they were
      larger in the girls. The differences, however, were not statistically
      significant. The volume of the calcaneal ossification center increased the most
      between the first and second years of life, reaching 183% and 140% in girls and
      boys, respectively. Using the normal values obtained from the first group, we
      correctly predicted the chronologic age in 91% of children in the validation
      group. Among the remaining 9%, the error in prediction of chronologic age never
      exceeded 1 age interval. CONCLUSIONS: The use of sonography provides a
      quantitative means of measuring calcaneal volume, and its use is feasible for
      determining skeletal age in children. The normal values we obtained may be used
      as a baseline for sonographic assessment of skeletal maturation and diagnosis of
      growth retardation.

PMID- 14595735
TI  - Doppler sonographic characteristics of umbilical and uterine arteries during oral
      glucose tolerance testing in healthy pregnant women.
AB  - PURPOSE: Studies have shown that maternal hyperglycemia may be associated with
      increased placental resistance to blood flow and possibly adverse perinatal
      outcomes. The aim of this study was to determine whether Doppler velocimetric
      dynamics change in the uterine and umbilical arteries in healthy pregnant women
      (without gestational diabetes) during acute hyperglycemia induced by oral glucose
      tolerance testing. METHODS: Flow in the umbilical and right and left uterine
      arteries was assessed by spectral Doppler sonographic examination of healthy
      pregnant women at 24-28 weeks' menstrual age. Four Doppler studies were conducted
      for each woman: 1 before oral administration of 100 g of glucose and 3 more at 1,
      2, and 3 hours after glucose administration. The systolic-to-diastolic ratio was
      calculated for the umbilical artery, and the resistance index was calculated
      separately for the left and right uterine arteries. RESULTS: All results of oral
      glucose tolerance testing were normal, and Doppler signals were obtained in all
      30 patients enrolled. No abnormal systolic-to-diastolic ratios or resistance
      indices were detected in any of the examinations. No significant differences in
      waveforms or resistance indices between the right and left uterine arteries were
      found during the various testing intervals. CONCLUSIONS: Acute hyperglycemia
      induced in healthy pregnant women does not affect blood flow velocimetric
      characteristics in the umbilical or uterine arteries at any stage of oral glucose
      tolerance testing.

PMID- 14595736
TI  - Normal growth and development of fetal external genitalia demonstrated by
      sonography.
AB  - PURPOSE: Our aim in this retrospective sonographic study was to describe the
      normal growth and development of fetal external genitalia. METHODS: We reviewed
      the sonograms of anatomically normally fetuses, obtained over a 5-year period,
      and measured transverse scrotal diameter or penile length in male fetuses and
      bilabial diameter in female fetuses. Transverse scrotal diameter was measured
      from the midpoint of the lateral scrotal wall to the midpoint of the opposite
      lateral wall; penile length, from the base of the shaft to the tip; and bilabial
      diameter, from the midpoint of the lateral labial margin to the midpoint of the
      opposite lateral labial margin. RESULTS: We examined sonograms from 1,182 fetuses
      and measured transverse scrotal diameter in 304 and penile length in 494 male
      fetuses and bilabial diameter in 384 female fetuses. The fetuses ranged from 14
      to 41 weeks' menstrual age. Transverse scrotal diameter, penile length, and
      bilabial measurements were highly correlated with menstrual age (r = 0.941, r =
      0.860, and r = 0.898, respectively). We found that growth of fetal external
      genitalia is similar to that for other parameters of fetal growth, such as
      biparietal diameter and femur length. CONCLUSIONS: The results of this study may
      be helpful in understanding the natural course of the growth and development of
      fetal external genitalia. In addition, the data we gathered may be useful in
      combination with other biometric data for estimating fetal age and may help in
      detecting abnormalities in the fetal external genitalia.

PMID- 14595737
TI  - Prenatal color Doppler sonographic evaluation of nuchal encirclement by the
      umbilical cord.
AB  - PURPOSE: The aim of this study was to assess whether Doppler flow velocimetry of
      the fetal middle cerebral and umbilical arteries is affected by nuchal
      encirclement by the umbilical cord (nuchal cord) in the prenatal period. PATIENTS
      AND METHODS: The position of the fetal umbilical cord was assessed on color
      Doppler sonography in pregnant women who were referred to our radiology
      department between September 14, 1998, and January 14, 2000. Pulsatility and
      resistance indices and the ratio of peak systolic blood flow velocity to
      diastolic velocity of the umbilical arteries and middle cerebral arteries of all
      fetuses were prospectively obtained with Doppler flow velocimetry. The fetuses
      were categorized into 2 groups: group 1 consisted of fetuses without sonographic
      evidence of nuchal cord and group 2 of fetuses with sonographic evidence of
      nuchal cord. The results were statistically analyzed with independent-groups t
      test. A p value of less than 0.05 was considered significant. RESULTS: During the
      study period, 230 pregnant women underwent sonographic examination of the fetus,
      and 68 fetuses were delivered. The sonographic examinations were performed at 24
      41 weeks' menstrual age. Of the 46 fetuses in group 1, 1 fetus had nuchal cord at
      delivery; of the 22 fetuses in group 2, 4 did not have nuchal cord at delivery.
      The sensitivity of color Doppler sonography in detecting nuchal cord was 95% (18
      of 19 fetuses), the specificity was 92% (45 of 49), the negative predictive value
      was 98% (45 of 46), and the positive predictive value was 82% (18 of 22). No
      statistically significant differences in middle cerebral artery or umbilical
      artery Doppler flow velocimetry values were detected between the 2 groups.
      CONCLUSIONS: Color Doppler sonography is a sensitive and specific method of
      diagnosing nuchal cord, but fetal middle cerebral artery and umbilical artery
      Doppler flow velocimetry values are not affected by the presence of nuchal cord
      in the prenatal period.

PMID- 14595738
TI  - Choledochal cysts in children: evaluation with three-dimensional sonography.
AB  - In this report, we describe the application of 3-dimensional (3D) sonography for
      diagnosing choledochal cysts in 3 girls who were 18 months, 2 years, and 11 years
      old. The 3D images that were obtained during the sonographic examination revealed
      that all 3 patients had a type I choledochal cyst and also demonstrated
      dilatation of the biliary tracts. The 3 patients then underwent surgical excision
      of their cysts, cholecystectomy, and hepaticojejunostomy. Besides its other
      clinical applications, 3D sonography promises to be a valuable adjunct to
      conventional 2-dimensional imaging for the evaluation of choledochal cysts in
      pediatric patients.

PMID- 14595739
TI  - Testicular hamartomas in Cowden disease.
AB  - We report a case of testicular hamartomas in association with Cowden disease.
      Clinical examination of the patient, a 39-year-old man, revealed a palpable mass
      in the right side of the scrotum. Sonographic examination showed that the mass
      was either a spermatocele or an epididymal cyst and that multiple hyperechoic
      lesions were present in both testes. On subsequent MRI, the appearance of these
      lesions was consistent with that of fat-containing hamartomas. Testicular biopsy
      was not performed, but follow-up serial sonographic examination was recommended.
      To our knowledge, this report is the first to describe testicular hamartomas as a
      probable manifestation of Cowden disease.

PMID- 14595740
TI  - Three-dimensional transvaginal sonography of interstitial pregnancy.
AB  - We describe the case of a 33-year-old pregnant woman, gravida 1 para 0, who was
      referred to us with a presumptive diagnosis of an interstitial pregnancy. The
      patient had had amenorrhea for 7 weeks and had previously undergone myomectomy.
      Two-dimensional sonographic examination revealed a gestational sac located
      outside the uterine cavity but could not define its exact anatomic position.
      Using transvaginal 3-dimensional sonography, we were able to correctly depict the
      sac, which was located where the fallopian tube crossed the uterine horn. We
      performed a cornual resection, during which the diagnosis of interstitial
      pregnancy was confirmed. The use of 3-dimensional sonography in this patient's
      case thus led to appropriate early treatment and avoidance of possible subsequent
      morbidity.

PMID- 14595741
TI  - Primary linitis plastica carcinoma of the colon accompanied by peritoneal
      abscess.
AB  - We describe the case of a 75-year-old woman with linitis plastica carcinoma of
      the colon, accompanied by a peritoneal abscess, in which the use of
      transabdominal sonography enabled prompt detection and diagnosis. Sonographic
      examinations revealed diffuse wall thickening with blurred layer stratification
      in the ascending colon. The irregular outer margin of the affected area was
      surrounded by thickened pericolic fat. A peritoneal abscess covered by the
      omentum was also found. CT confirmed these findings. We extensively resected the
      right half of the colon. Histopathologic examination of the excised segment of
      the colon revealed a poorly differentiated adenocarcinoma with fibrotic
      infiltration. The patient was discharged 6 weeks postoperatively, and
      chemotherapy was begun, but she was lost to our follow-up. Although linitis
      plastica carcinoma of the colon is rare, it must be considered when patients have
      extensive colonic wall thickening with blurred layer stratification and an
      irregular outer margin surrounded by thickened pericolic fat. Transabdominal
      sonography should be considered the imaging modality of choice for the detection
      and diagnosis of this disease entity.

PMID- 14595742
TI  - Sonographic appearance of a congenital parotid gland hemangiolymphangioma
      simulating malignancy in an infant.
AB  - Congenital hemangiolymphangioma, also called mixed angioma, is a benign tumor
      that very rarely occurs in the parotid gland. We present a rare case of
      hemangiolymphangioma of the parotid gland in a 4-month-old boy whose clinical and
      radiologic presentation simulated malignancy. Gray-scale and color Doppler
      sonography revealed an enlarged left parotid gland and inhomogeneous hypoechoic
      and hyperechoic areas scattered throughout the gland. Mild internal vascularity
      was noted on color Doppler sonographic examination. CT revealed a predominantly
      fatty mass involving the superficial lobe of the parotid gland. The results of
      fine-needle aspiration cytology were inconclusive, and total parotidectomy was
      performed. Histopathologic examination of surgical specimens confirmed a
      diagnosis of hemangio lymphangioma. The patient recovered well and was free of
      recurrence at the 6-month follow-up visit. To our knowledge, this case report is
      the first to describe the findings of congenital hemangiolymphangioma of the
      parotid gland on sonography and CT. This rare diagnosis should be considered in
      neonates and infants presenting with a rapidly growing parotid gland tumor
      suggesting malignancy. Histopathologic examination is necessary to confirm the
      diagnosis.

PMID- 14595743
TI  - Idiopathic infantile arterial calcification: sonographic findings.
AB  - Idiopathic infantile arterial calcification (IIAC) is a rare disease that is
      characterized by calcification in the media and fibroproliferative changes in the
      intima of larger arteries, sometimes resulting in reduced vascular elasticity and
      blood flow. Although the molecular-genetic basis of the disease is unknown, IIAC
      is presumed to be acquired by an autosomal recessive mode of inheritance and is
      associated with a reduction in the levels of enzymes responsible for inorganic
      phosphate balance, resulting in abnormal deposition of calcium into the vessels.
      We report the case of a female neonate in whom widespread IIAC was initially
      diagnosed on postnatal sonographic examination. At birth, the infant experienced
      cardiac failure and hypertension, and arterial pulsation was absent. Routine
      prenatal sonographic examinations had not revealed any abnormalities, but
      postnatal gray-scale and color Doppler echocardiographic and sonographic
      examinations revealed findings consistent with severe IIAC. The cardiac function
      improved with treatment, but the neonate died of progressive hepatic failure due
      to reduced flow in calcified and narrowed hepatic arteries. The common carotid
      arteries were also grossly affected, resulting in cerebral atrophy at the time of
      birth. Postnatal gray-scale and color Doppler echocardiographic and sonographic
      examinations allowed noninvasive diagnosis, assessment of severity, and
      monitoring of progression.

PMID- 14595746
TI  - Cadherins, catenins and APC in pleural malignant mesothelioma.
AB  - Malignant mesothelioma is an aggressive disease of the pleura, and less commonly
      the peritoneum, with a very poor prognosis. The present study has examined the
      expression of cell adhesion molecules including cadherins, catenins, and APC in
      order to determine whether abnormal expression of components of the Wnt
      signalling pathway contribute to the variable phenotype of malignant
      mesothelioma. Sixty-three malignant mesotheliomas and nine cases of reactive
      mesothelial hyperplasia were analysed by immunohistochemistry for E-cadherin, N
      cadherin, alpha-catenin, beta-catenin, and the C- and N-terminals of APC. In
      addition, DNA was extracted from formalin-fixed, paraffin wax blocks, and a 226
      bp fragment of exon 3 of the beta-catenin gene was amplified, sequenced, and
      screened for activating mutations in the glycogen synthase kinase 3beta (GSK
      3beta) phosphorylation targets. E-cadherin expression was detected in 48% of the
      epithelioid mesotheliomas but was observed in only 7% of sarcomatoid
      mesotheliomas. N-cadherin, alpha-catenin, beta-catenin, and the C- and N
      terminals of APC did not show differential expression between the mesothelioma
      phenotypes. Abnormal nuclear localization of beta-catenin was demonstrated in 19%
      of mesotheliomas. Mutations of beta-catenin phosphorylation sites were not
      detected in any of the 62 mesotheliomas examined. Positive staining for the N
      terminal of APC was seen in all of the cases of reactive mesothelial hyperplasia,
      as well as in all the mesotheliomas. Staining for the C-terminal of APC was
      negative in 23% mesotheliomas, despite being present in all the cases of reactive
      hyperplasia. The present study provides the first evidence that beta-catenin
      accumulates in the nucleus in malignant mesotheliomas. In addition, APC
      expression was altered in some mesotheliomas, suggesting that a truncated APC
      gene product may contribute to abnormal Wnt signalling and dysregulation of cell
      proliferation in malignant mesothelioma.

PMID- 14595747
TI  - Expression of the thioredoxin system in interstitial lung disease.
AB  - The thioredoxin system containing thioredoxin (Trx) and thioredoxin reductase
      (TrxR) has profound effects on cell proliferation and protection against
      exogenous oxidants. The significance of the Trx system in human lung and lung
      diseases is, however, largely unresolved. Altogether, 66 specimens of human lung
      were investigated by immunohistochemistry for their expression of Trx and TrxR.
      The diseases included interstitial pneumonias such as usual interstitial
      pneumonia (UIP), desquamative interstitial pneumonia (DIP), and UIP associated
      with collagen vascular diseases (CVD-ILD), and granulomatous diseases such as
      sarcoidosis and allergic alveolitis. The ultrastructural localization of Trx and
      TrxR was analysed by immunoelectron microscopy. In healthy lung, Trx and TrxR
      were expressed in bronchial epithelium and alveolar macrophages. Trx and TrxR
      were highly concentrated in areas of metaplastic epithelium in UIP and in
      alveolar macrophages in DIP, though fibrotic areas in UIP were mainly negative.
      The expression of both enzymes was clearly weaker in CVD-ILD than in UIP.
      Granulomas of sarcoidosis showed moderate to intense Trx immunoreactivity.
      Ultrastructurally, Trx and TrxR were expressed diffusely in the cytosolic
      compartment and plasma membrane of metaplastic type II pneumocytes, macrophages,
      and bronchial epithelial cells. This study highlights the importance of Trx and
      TrxR in primary defence in bronchial epithelium, alveolar epithelium, and
      macrophages in human lung, but also indicates that elevated expression of these
      proteins may serve as markers of ongoing cell regeneration and inflammation.

PMID- 14595748
TI  - Is high-grade adenomatous hyperplasia an early bronchioloalveolar adenocarcinoma?
AB  - Atypical adenomatous hyperplasia (AAH) is a probable forerunner of
      bronchioloalveolar carcinoma (BAC) and pulmonary adenocarcinoma (AC) of mixed
      type. The present study analysed four low-grade AAHs, 13 high-grade AAHs, two
      BACs, nine mixed ACs, and one squamous cell carcinoma derived from 13 patients
      using comparative genomic hybridization. The average number of chromosomal
      aberrations was 1.2 in low-grade AAH, 9.6 in high-grade AAH, and 12.5 in AC. A
      high degree of overlap of genetic changes was found in high-grade AAH, BAC, and
      AC within individual patients. The high number of aberrations and the degree of
      shared aberrations found in high-grade AAH and AC raises questions about the
      separation of these two entities. In addition, in view of the monoclonal origin
      of multiple foci within the same patient, AAH may not be a precursor of AC in
      some cases, but rather may represent intraepithelial spread.

PMID- 14595745
TI  - Pathogenetic mechanisms in usual interstitial pneumonia/idiopathic pulmonary
      fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is a progressive, usually fatal, form of
      interstitial lung disease characterized by failure of alveolar re
      epithelialization, persistence of fibroblasts/myofibroblasts, deposition of
      extracellular matrix, and distortion of lung architecture which ultimately
      results in respiratory failure. Clinical IPF is associated with a
      histopathological pattern of usual interstitial pneumonia (UIP) on surgical lung
      biopsy. Therapy for this disease with glucocorticoids and other immunomodulatory
      agents is largely ineffective and recent trials of newer anti-fibrotic agents
      have been disappointing. While the inciting event(s) leading to the initiation of
      scar formation in UIP remain unknown, recent advances in our understanding of the
      mechanisms underlying both normal and aberrant wound healing have shed some light
      on pathogenetic mechanisms that may play significant roles in this disease.
      Unlike other fibrotic diseases of the lung, such as those associated with
      collagen vascular disease, occupational exposure, or chemotherapeutic agents, UIP
      is not associated with a significant inflammatory response; rather, dysregulated
      epithelial-mesenchymal interactions predominate. Identification of pathways
      crucial to fibrogenesis might offer potentially novel therapeutic targets to slow
      or halt the progression of IPF. This review focuses on evolving concepts of
      cellular and molecular mechanisms in the pathogenesis of UIP/IPF.

PMID- 14595749
TI  - Tissue-specific p53 responses to ionizing radiation and their genetic
      modification: the key to tissue-specific tumour susceptibility?
AB  - Although little is understood of the underlying mechanisms, there are tissue
      specific responses to tumourigenic and therapeutic agents and these responses are
      influenced by genetic factors. Ionizing radiation is an important tumourigenic
      and therapeutic agent for which there is substantial evidence for such tissue
      dependent and genotype-dependent responses. Because the p53 tumour suppressor
      protein is a major determinant of cellular responses to radiation, the present
      study has investigated whether modification of the p53 pathway contributes to
      tissue-dependent and genotype-dependent responses using inbred strains of mice.
      Comparison of responses in haemopoietic and epithelial cells in irradiated
      C57BL/6 and DBA/2 mice revealed significant differences in p53 and apoptotic
      responses in different cell types and in different cells of the same type,
      reflecting the complexity of damage responses operating in the whole organism.
      The data suggest that p53-mediated up-regulation of Bax is a major determinant of
      apoptosis in the spleen, but not in the intestine, whereas p53-mediated induction
      of p21(waf1) plays an anti-apoptotic role in the spleen, but not in the
      intestine. It is also shown that p53 stabilization and differential
      transactivational activities towards Bax or p21(waf1) are influenced by genetic
      factors that act in a tissue-specific manner. Analysis of ATM, a potential
      mediator of differential p53 activation, indicates that this key regulator of
      radiation responses is preferentially induced in epithelial cells, but is
      unlikely to account for genetic modification of p53 or apoptotic responses in the
      mouse strains studied. Polymorphisms in the p53 or DNA-PKcs genes are also
      unlikely to account for the genetic modifications that are reported here. There
      are numerous further potential modifiers of the p53 pathway, but analysis of
      backcross and inter-cross mice demonstrates that genes responsible for the
      complex modification of these in vivo responses can be identified by linkage
      analysis. This approach has the potential to reveal new or unexpected
      interactions involving the p53 pathway that determine both short-term and long
      term effects of radiation exposure and the basis of tissue-specific responses and
      tumour susceptibility.

PMID- 14595750
TI  - MSI-low, a real phenomenon which varies in frequency among cancer types.
AB  - This study assessed whether low-level microsatellite instability (MSI-L) is a
      phenomenon specific to colorectal cancers or is also present in other tumour
      types. Breast (grade III ductal and lobular), endometrial and ovarian carcinomas,
      as well as colorectal cancers, were analysed for MSI-L using eight microsatellite
      markers. The markers were selected from a panel that had previously been shown to
      be sensitive for the detection of MSI-L in colorectal cancers. It was found that
      MSI-L was present in 30 of 87 (35%) colorectal cancers, 2 of 59 (3%) grade III
      breast carcinomas, 1 of 35 (3%) lobular breast cancers, 16 of 50 (32%)
      endometrial cancers, and 9 of 34 (26%) ovarian cancers. These results suggest
      that MSI-L is a very rare occurrence in breast carcinomas, but does occur as a
      real phenomenon in colorectal, endometrial, and ovarian carcinomas, which are all
      part of the hereditary non-polyposis colon cancer (HNPCC) syndrome. PCR artefact
      was also found to masquerade as MSI-L; criteria for the assessment of MSI-L are
      suggested to eliminate this problem.

PMID- 14595751
TI  - Induction of contact-dependent endothelial apoptosis by osteosarcoma cells
      suggests a role for endothelial cell apoptosis in blood-borne metastasis.
AB  - Although tumour cells are believed to migrate between endothelial cells early in
      metastasis, the possibility remains that endothelial apoptosis may also
      contribute to the tumour's breach of the vascular barrier. Although seemingly
      inconsistent with tumour angiogenesis, one publication describes the induction of
      contact-dependent apoptosis in cultured endothelium by tumour cells. The cell
      culture data are, however, open to challenge on technical grounds while there are
      no confirmatory reports. The present paper describes experiments overcoming these
      limitations. SAOS-2 human osteosarcoma cells and two rat carcinoma cell lines
      were co-cultured with human umbilical vein endothelial cells (HUVECs) and
      cultures labelled by surface lectin histochemistry for endothelium. The HUVEC
      culture density was determined and SAOS-2 cells, but not rat carcinoma cells,
      were found significantly to reduce HUVEC survival despite the release of potent
      growth factors as determined in separate experiments with tumour cell conditioned
      medium. Lectin labelling combined with light microscopy, transmission electron
      microscopy, flow cytometry for both lectin binding and DNA content, and DNA gel
      electrophoresis of SAOS-2/HUVEC co-cultures revealed extensive HUVEC apoptosis.
      These findings indicate contact-dependent endothelial apoptosis by SAOS-2, while
      this activity appeared weaker and overwhelmed by HUVEC proliferation with rat
      carcinoma cells. Importantly, this study supports the suggestion that endothelial
      apoptosis may be important for metastasis and suggests a complex interplay
      between endothelial proliferation and apoptosis in tumours.

PMID- 14595753
TI  - Inactivating I kappa B epsilon mutations in Hodgkin/Reed-Sternberg cells.
AB  - The pathogenesis of Hodgkin lymphoma (HL) is still unclear. Previous
      investigations have demonstrated constitutive nuclear activity of the
      transcription factor NF kappa B (NF-kappaB) in Hodgkin/Reed-Sternberg (HRS) cells
      as an important prerequisite in protecting these cells from apoptosis. As a
      molecular mechanism leading to constitutive NF-kappaB activity in HRS cells,
      mutations of the NF-kappaB inhibitor I kappa B alpha (IkappaBalpha) have recently
      been identified in classical (c) HL-derived cell lines in a patient with cHL. In
      the present study, the NF-kappaB inhibitor I kappa B epsilon (IkappaBepsilon) has
      been analysed for somatic mutations in the same group of six patients already
      studied for IkappaBalpha mutations, as well as in cHL-derived cell lines. In one
      cHL-derived cell line (L428), a hemizygous frame-shift mutation generating a pre
      terminal stop codon resulting in a severely truncated protein was found.
      Moreover, in the HRS cells of one patient, a hemizygous mutation affecting the 5'
      splicing site of intron 1 of the IkappaBepsilon gene was found. These results, in
      combination with recently described IkappaBalpha mutations, indicate that
      defective NF-kappaB inhibitors appear more frequent than previously thought and
      might explain the constitutive nuclear activity of NF-kappaB in a significant
      proportion of cHL cases.

PMID- 14595752
TI  - Germinal centre-like versus undifferentiated stromal immunophenotypes in
      follicular lymphoma.
AB  - Follicular dendritic cells (FDCs) in reactive germinal centres (GCs) show
      modulated expression of antigens indicative of step-wise maturation from more
      undifferentiated stroma. The present study compared the expression of FDC markers
      CD21, CD23, CD35, and chemokine CXCL13 and the stromal markers low-affinity nerve
      growth factor receptor (LNGFR) and CNA.42 in 35 follicular lymphoma (FL) cases
      with reactive lymphoic tissue. CXCL13 was expressed by follicular stroma in all
      FLs but most cases showed either partial (11/35 cases, 31%) or complete (10/35
      cases, 29%) absence of other FDC antigens, most commonly CD23, followed by CD21
      and CD35, with variable patterns of LNGFR and CNA.42 immunostaining. Only a
      minority of FL cases (14/35, 40%) showed stroma that resembled mature FDCs
      (CD23+, CD21+, CD35+) and these tumours were always associated with numerous
      intrafollicular T-cells, similar to reactive GCs. In the 25 FL cases that had
      identifiable extrafollicular tumour cells, the immunophenotype of follicular
      stroma showed the same variability but the extrafollicular stroma showed an
      absence of FDC markers, with the exception of frequent strong LNGFR staining.
      Stromal phenotypic changes in FL were not correlated with mean follicle size,
      percentage of diffuse growth, tumour mitotic rate or the proliferation index as
      determined by PCNA immunostaining. Serial biopsy specimens analysed in a subset
      of 15 patients showed either a stable stromal phenotype (seven cases, 47%) or
      loss of FDC antigens in tumour-associated stroma over time (seven cases, 47%).
      The GC-like subset of FLs, having both abundant intrafollicular T-cells and fully
      differentiated CD23+ FDCs, comprises a minority of FL cases that likely have
      different growth requirements from FLs that lack these features. The pattern of
      FDC antigen loss in stroma of FL is a readily assessable biological feature that
      appears independent of architectural growth pattern and may serve as a useful
      surrogate marker of tumour progression.

PMID- 14595754
TI  - Chromosomal imbalances: a hallmark of tumour relapse in primary cutaneous CD30+ T
      cell lymphoma.
AB  - Primary cutaneous CD30+ large T-cell lymphoma (CD30+ CTCL) is a subset of non
      epidermotropic primary cutaneous T-cell lymphoma. Although frequent spontaneous
      regression may be observed, skin relapses occur frequently. Cytogenetic
      abnormalities that could play a role in CD30+ CTCL tumour pathogenesis and
      relapses remain unknown. The identification of recurrent cytogenetic
      abnormalities is hampered by difficulty in culturing tumours and the lack of
      CD30+ CTCL serial studies comparing genetic changes both at diagnosis and at
      relapse. The purpose of this study was to investigate the cytogenetic
      abnormalities present in a series of 13 CD30+ CTCL samples obtained from nine
      patients fulfilling both EORTC and WHO diagnostic criteria, by the use of
      comparative genomic hybridization (CGH). CGH analysis revealed a non-random
      distribution of genetic imbalances between relapsing and non-relapsing disease.
      In relapsing disease, chromosomal abnormalities were detected both in the primary
      tumour and in relapses. The mean number of changes in non-relapsing disease was
      0.33 (range 0-1), compared with 6.29 (range 1-16) in relapsing disease. The
      recurrent chromosomes involved in relapsing disease were chromosomes 6 (86%), 9
      (86%), and 18 (43%). While chromosome 9 was mostly affected by gain, chromosomes
      6 and 18 mainly contained regions of loss, exclusively on 6q and 18p. The common
      regions of deletion were 6q21 and 18p11.3. In one patient, we successfully
      cultured tumour cells from a skin biopsy from a second relapse. The G-banded
      karyotype was concordant with both CGH and fluorescence in situ hybridization
      (FISH) results. Although further studies are required to strengthen these data,
      this CGH analysis demonstrates chromosomal imbalances that may be involved in the
      pathogenesis of relapsing CD30+ CTCL.

PMID- 14595755
TI  - Gastric cancer: the role of insulin-like growth factor 2 (IGF 2) and its
      receptors (IGF 1R and M6-P/IGF 2R).
AB  - Insulin-like growth factor 2 (IGF 2) appears to be involved in the progression of
      many tumours. It binds to at least two different types of receptor: IGF type 1
      (IGF 1R) and mannose 6-phosphate/IGF type 2 (M6-P/IGF 2R). Ligand binding to IGF
      1R provokes mitogenic and anti-apoptotic effects. M6-P/IGF 2R has a tumour
      suppressor function--it mediates IGF 2 degradation. Mutation of M6-P/IGF 2R
      causes both diminished growth suppression and augmented growth stimulation. The
      aim of this study was to investigate the role of IGF 2 and its receptors (IGF 1R
      and IGF 2R) in human gastric cancer. The expression of IGF 2 and its receptors
      was measured in order to analyse the possible correlation between the activity of
      these genes and cell proliferation in two different gastric tumour types: diffuse
      and intestinal. The effect of IGF 1 receptor blockage on cell proliferation and
      anchorage-independent cell growth was also examined. Increased expression of IGF
      2 and IGF 1R genes (at the mRNA and protein level) was found in gastric cancer
      when compared with non-tumour tissue. Furthermore, there was a significant
      difference between IGF 2 expression in the more aggressive diffuse type and that
      in the intestinal type of gastric cancer. Moreover, the IGF 2 peptide level in
      the culture media obtained from the diffuse type of cancer cells was
      significantly higher when compared with the intestinal type. The level of IGF 2
      peptide in the conditioned media strongly correlated with [3H]thymidine
      incorporation and cell proliferation. On the contrary, IGF 2R mRNA expression was
      much higher in the intestinal type of cancer than in the diffuse type. In
      addition, IGF 2R protein expression was substantially lower with progression of
      the diffuse cancer type to a higher stage. The alphaIR3 monoclonal antibody
      strongly inhibited [3H]thymidine incorporation and decreased the number of
      colonies in soft agar of cells overexpressing IGF 2. These findings suggest that
      members of the IGF family are involved in the pathogenesis of gastric cancer,
      probably by autocrine/paracrine stimulation of cell growth. Such tumours might be
      excellent candidates for therapeutic strategies aimed at interference with this
      pathway.

PMID- 14595756
TI  - Alterations of chromosomal copy number during progression of diffuse-type gastric
      carcinomas: metaphase- and array-based comparative genomic hybridization analyses
      of multiple samples from individual tumours.
AB  - The application of comparative genomic hybridization (CGH) has led to the rapid
      accumulation of cytogenetic information on gastric carcinoma (GC), but there is
      little information on the time sequence of cytogenetic changes. In the present
      study, degenerate oligonucleotide-primed polymerase chain reaction (DOP-PCR) and
      CGH were applied to multiple samples microdissected from 19 diffuse-type GCs
      including eight early cancers. Recurrent gains were detected at 8q, 3q, 7q, and
      8p, and loss at 17p (in more than 50% of the cancers), the frequencies of which
      were fairly similar between the samples with (SIG) and those without (POR)
      abundant signet ring cells. Earlier stemline changes (8q+, 8p+, 1q+, 17p-, etc),
      with breakpoints that were common to all the samples, were discriminated from
      later sideline changes (2q+, 11q+, 17q-, 21q-, etc) in individual tumours. The
      changes were generally common to early and advanced cancers, except for 7p+,
      15q+, 3p-, and 18q-, which were largely sideline changes and more frequently
      detected in advanced cancers (p<0.05). Because the samples with 7p+ had a greater
      number of copy-number changes than those without 7p+ (p<0.01), 7p+ may play a
      role in tumour progression by acceleration of chromosomal instability. Fifteen
      different chromosomal loci with amplification were detected in ten cases, mostly
      as sideline changes in advanced cancers. By microarray-based CGH, KRAS, MDM2, and
      FGFR2 were confirmed in the amplicons at 12p, 12q, and 10q, and FES at 15q26, for
      the first time in GC. These results support the notion that SIG and POR are of a
      genetically single lineage in both early and advanced diffuse-type GC and that
      the majority of advanced cancers derive from early cancers through the
      accumulation of various sideline changes in addition to stemline changes.

PMID- 14595757
TI  - Expression of p27kip1 in breast cancer and its prognostic significance.
AB  - p27kip1 is a member of the KIP/CIP family of cyclin-dependent kinase inhibitors
      and is a negative cell-cycle regulator that is thought to play a role in tumour
      suppression. Reduced levels of this protein have been observed in a number of
      human cancers. However, evidence is conflicting as to whether p27kip1 has a role
      to play in breast cancer, including predicting behaviour and prognosis. The
      present investigation aimed to provide a definitive study of 830 breast cancer
      cases with median patient follow-up of 104 months to determine the true
      prognostic significance, if any. Immunohistochemical analysis of tissue
      microarrays and three scoring methods were used to assess p27kip1 expression.
      Univariate analysis showed a significant relationship between reduced p27kip1
      expression and increasing tumour grade, nuclear pleomorphism, mitosis, and
      decreasing tubule formation (all p<0.001). Significant associations between
      reduced p27, negative oestrogen receptor status, and ductal/no special type
      tumours were also observed. Survival analysis demonstrated that patients with
      tumours with high p27kip1 levels had an improved survival compared with those
      with cancers with low expression. On multivariate analysis, when compared with
      existing factors, p27kip1 was not, however, an independent prognostic factor. It
      is concluded that the inverse relationship between p27kip1 levels and
      histological grade and individual grade components suggests a role for p27kip1 in
      both cell proliferation and differentiation, but is not clinically useful.

PMID- 14595758
TI  - Nuclear beta-catenin is a molecular feature of type I endometrial carcinoma.
AB  - Two types of endometrial carcinoma can be distinguished: type I tumours, which
      are oestrogen-related and are typically low-grade endometrioid carcinomas; and
      type II tumours, which are unrelated to oestrogen stimulation and are often non
      endometrioid carcinomas. The molecular abnormalities involved in carcinogenesis
      appear to be different for these tumour types. The aim of this study was to test
      the hypothesis that an abnormality in the Wnt/beta-catenin signalling pathway is
      a molecular feature of type I endometrial carcinoma. This study investigated
      nuclear beta-catenin by immunohistochemistry in 233 endometrial carcinomas and
      analysed its correlation with several immunohistochemical, histological, and
      clinical parameters, such as proliferation rate (Ki-67), expression of oestrogen
      and progesterone receptors, and survival. Nuclear beta-catenin expression was
      observed in 39 cases (16%). All tumours expressing nuclear beta-catenin were
      endometrioid adenocarcinomas, were significantly better differentiated, and were
      more often hormone receptor-positive than tumours without nuclear beta-catenin.
      No correlation with proliferation rate was found. It was found that several
      features of type I endometrial carcinoma occur significantly more often in
      tumours expressing nuclear beta-catenin, suggesting that an abnormality in the
      Wnt/beta-catenin signalling pathway, resulting in nuclear beta-catenin
      immunopositivity, is a molecular feature of a subset of type I endometrial
      carcinomas.

PMID- 14595759
TI  - NF-kappaB expression in oral and cutaneous lichen planus.
AB  - Lichen planus (LP) is a chronic inflammatory disorder involving cutaneous and
      mucosal surfaces, characterized by a T-cell-mediated immune response against
      epithelial cells, with persistent accumulation of T lymphocytes and epithelial
      cell damage. The mechanisms involved in this chronic inflammatory disease are
      largely unknown. A pivotal role in the pathogenesis of long-lasting inflammatory
      processes is played by the activation of nuclear factor kappa B (NF-kappaB), a
      primary transcription factor which upon translocation to the nucleus, binds to
      promoter regions of different genes encoding immune and pro-inflammatory
      mediators. Using immunohistochemistry, the present study analysed the expression
      of NF-kappaB in 25 cases of cutaneous LP (CLP) and 28 cases of oral LP (OLP) and
      correlated this with the recruitment of cytotoxic T-cells (expressing Tia-1 or
      perforin) in the inflammatory infiltrate. Nuclear NF-kappaB was expressed on
      basal and suprabasal keratinocytes in all cases of LP, while normal epithelium
      was consistently negative; OLP contained significantly higher numbers of NF
      kappaB-positive keratinocytes than CLP (means: 89.32 versus 22.6; p<0.05).
      Furthermore, nuclear NF-kappaB expression by epithelial cells correlated with the
      amount of cytotoxic cell infiltration (p<0.02). These data suggest that increased
      NF-kappaB activity may represent the basis of maintenance of the inflammatory
      response. The differences observed between NF-kappaB expression on epithelial
      cells in OLP and CLP and their correlation with the degree of cytotoxic
      inflammatory infiltrate might explain the different clinical courses of the two
      variants of the disease, since OLP is typically more recalcitrant than CLP. As
      proposed for other chronic inflammatory disorders associated with increased NF
      kappaB activity, the involvement of NF-kappaB in the pathogenesis of LP could be
      considered for selective therapeutic inhibitory targeting.

PMID- 14595760
TI  - Loss of parental-specific methylation at the IGF2 locus in human hepatocellular
      carcinoma.
AB  - Significant production of the growth factor IGF2 has been reported in human
      hepatocellular carcinomas (HCCs). Disturbances associated with changes in
      methylation at this locus or affecting the 11p15.5 imprinting domain as a whole
      can be postulated in HCCs. In the present study, the methylation status of
      differentially methylated regions of the imprinted genes TSSC5, LIT1, and IGF2,
      which span the 11p15 domain, was analysed in 71 liver tissues from virus
      associated and non-virus-associated HCCs compared with six normal liver tissues.
      Altered methylation of TSSC5 and LIT1 was observed in only 6% and 8% of HCCs,
      respectively, compared with 89% at the IGF2 locus, suggesting that these loci
      were not concomitantly dysregulated. These observations suggest that loss of
      parental-specific methylation at the IGF2 locus may be specifically associated
      with HCC, whether virus-associated or non-virus-associated, and arising in
      cirrhotic or non-cirrhotic livers.

PMID- 14595761
TI  - SDHD mutations in head and neck paragangliomas result in destabilization of
      complex II in the mitochondrial respiratory chain with loss of enzymatic activity
      and abnormal mitochondrial morphology.
AB  - Hereditary head and neck paragangliomas are tumours associated with the autonomic
      nervous system. Recently, mutations in genes coding for subunits of mitochondrial
      complex II, succinate-ubiquinone-oxidoreductase (SDHB, SDHC, and SDHD), have been
      identified in the majority of hereditary tumours and a number of isolated cases.
      In addition, a fourth locus, PGL2, has been mapped to chromosome 11q13 in an
      isolated family. In order to characterize phenotypic effects of these mutations,
      the present study investigated the immunohistochemical expression of the
      catalytic subunits of complex II (flavoprotein and iron protein), SDH enzyme
      activity, and mitochondrial morphology in a series of 22 head and neck
      paragangliomas. These included 11 SDHD-, one SDHB-, two PGL2-linked tumours, and
      eight sporadic tumours. In the majority of the tumours (approximately 90%), the
      enzyme-histochemical SDH reaction was negative and immunohistochemistry of
      catalytic subunits of complex II showed reduced expression of iron protein and
      enhanced expression of flavoprotein. Ultrastructural examination revealed
      elevated numbers of tightly packed mitochondria with abnormal morphology in SDHD
      linked and sporadic tumours. Immuno-electron microscopy showed localization of
      the flavoprotein on the remnants of the mitochondrial inner membranes, whereas
      virtually no signal for the iron protein was detected. These results indicate
      that the function of mitochondrial complex II is compromised in the majority of
      head and neck paragangliomas.

PMID- 14595762
TI  - Mechanisms of inactivation of the p16INK4a gene in leiomyosarcoma of soft tissue:
      decreased p16 expression correlates with promoter methylation and poor prognosis.
AB  - The p16INK4a tumour suppressor gene, encoding p16 protein, plays a crucial role
      in regulation of the G1 cell-cycle phase. To investigate the potential role of
      p16 in soft tissue leiomyosarcoma (LMS), an immunohistochemical analysis was
      performed of 77 LMSs for p16 expression. Decreased expression of the p16 protein
      was identified in 25 of 77 LMSs (32%). Decreased expression of p16 correlated
      significantly with large tumour size (p=0.0038). In a univariate analysis, large
      tumour size and decreased expression of p16 were statistically significant
      adverse prognostic factors (p=0.025 and p=0.0021, respectively). In a
      multivariate analysis including conventional clinicopathological parameters,
      decreased expression of p16 protein was revealed as the only independent
      unfavourable prognostic factor (p=0.012). To elucidate the mechanisms of
      inactivation of the p16INK4a gene, 49 LMSs for which genomic DNA was available
      were examined; analysis for homozygous deletion, mutation, and promoter
      hypermethylation was conducted using differential PCR, PCR-SSCP, and methylation
      specific PCR, respectively. Promoter hypermethylation was detected in 11 of 49
      LMS cases (22%); homozygous deletion was detected in 3 of 49 cases (6%); and
      mutation was not recognized in any of the cases studied. Eight of 15 cases (53%)
      with decreased expression of p16 protein revealed methylation of the p16INK4a
      gene promoter. Promoter hypermethylation correlated closely with decreased
      expression and poor prognosis (p=0.0014 and p=0.0088, respectively). These
      results suggest that decreased expression of p16 protein can be considered as an
      independent reliable prognostic parameter in patients with soft tissue LMS.
      Furthermore, promoter methylation was more frequent than either homozygous
      deletion or mutation in this tumour, and promoter methylation was also shown to
      have a strong association with inactivation of the p16INK4a gene.

PMID- 14595763
TI  - Apoptosis of terminal hypertrophic chondrocytes in an in vitro model of
      endochondral ossification.
AB  - It is widely accepted that growth plate chondrocytes undergo apoptosis when they
      reach the terminal hypertrophic stage of their differentiation during the process
      of endochondral ossification in vivo. In this report, an established chondrocyte
      cell culture model of mammalian endochondral ossification was utilized to
      investigate the fate of chondrocytes after they had entered hypertrophy in vitro.
      Fetal bovine epiphyseal chondrocytes were treated with the demethylating agent, 5
      azacytidine, for 48 h and then cultured under azacytidine-depleted conditions.
      There was evidence for apoptosis in azacytidine-treated cells, as demonstrated by
      nuclear condensation and fragmentation (days 27 and 35) using transmission
      electron microscopy, and the detection of exposed phosphatidylserine on the
      plasma membrane surface of apoptotic chondrocytes (day 27) using fluorescence
      labelled annexin V. Treated cultures on days 10 and 20 and untreated cultures at
      all corresponding time-points showed no morphological characteristics of
      apoptosis. In situ hybridization studies of treated cultures revealed that
      expression of the apoptotic suppressor, bcl-2, remained consistently high
      throughout the culture period, whilst the apoptotic inducer, bax, was not
      expressed until day 23. Quantification of these data showed a gradual shift in
      the ratio of the expression level of bcl-2 and bax in favour of bax with time in
      culture, particularly from day 23 onwards. Taken together, the results indicate
      that azacytidine-treated epiphyseal chondrocytes entered terminal hypertrophy
      from day 23 onwards in culture and died by apoptosis. This study confirms this
      culture system as a successful recapitulation of the entire mammalian chondrocyte
      differentiation pathway, including apoptosis. The culture model will prove
      valuable for studies of the apoptotic fate of terminally differentiated
      chondrocytes in the growth plate with a view to providing a better understanding
      of the underlying mechanisms of skeletal malformations and other pathological
      disorders such as osteoarthritis.

PMID- 14595764
TI  - Apoptotic gene expression in Paget's disease: a possible role for Bcl-2.
AB  - Paget's disease of bone is characterized by an increase in both the size and the
      number of bone-resorbing osteoclasts. An important regulator of osteoclast
      activity is the process of apoptosis, and any aberration in this process could
      lead to increased osteoclasis. Analysis using human apoptosis cDNA expression
      arrays revealed that the apoptotic suppressor, Bcl-2, showed a marked increase in
      expression in Pagetic bone. In situ hybridization (ISH) and computer-assisted
      image analysis confirmed that the levels of Bcl-2 transcripts were significantly
      (p<0.0001) increased in Pagetic osteoclasts. The Bcl-2:Bax transcript ratios were
      similarly elevated. These findings were confirmed by immunohistochemistry. The
      Bcl-2 gene promoter sequence from 20 Pagetic patients and controls was analysed.
      Single nucleotide mutations were identified in three of the Paget's patients and
      one of the controls. Luciferase reporter analysis showed that the mutations
      induced a basal 12-fold increase and hydrogen peroxide-induced 19-fold increase
      in luciferase expression, compared with the normal construct. It is concluded
      that in Paget's disease, there is an increase in the expression of genes that are
      involved in the inhibition of apoptosis, notably Bcl-2. The increase in Bcl-2 may
      be explained in some patients by mutations in the Bcl-2 gene promoter. These
      results provide a potential explanation for the dramatic increase in osteoclasis
      seen in patients with Paget's disease.

PMID- 14595765
TI  - Cell type- and region-specific expression of protein kinase C-substrate mRNAs in
      the cerebellum of the macaque monkey.
AB  - We performed nonradioactive in situ hybridization histochemistry in the monkey
      cerebellum to investigate the localization of protein kinase C-substrate (growth
      associated protein-43 [GAP-43], myristoylated alanine-rich C-kinase substrate
      [MARCKS], and neurogranin) mRNAs. Hybridization signals for GAP-43 mRNA were
      observed in the molecular and granule cell layers of both infant and adult
      cerebellar cortices. Signals for MARCKS mRNA were observed in the molecular,
      Purkinje cell, and granule cell layers of both infant and adult cortices.
      Moreover, both GAP-43 and MARCKS mRNAs were expressed in the external granule
      cell layer of the infant cortex. In the adult cerebellar vermis, signals for both
      GAP-43 and MARCKS mRNAs were more intense in lobules I, IX, and X than in the
      remaining lobules. In the adult hemisphere, both mRNAs were more intense in the
      flocculus and the dorsal paraflocculus than in other lobules. Such lobule
      specific expressions were not prominent in the infant cerebellar cortex. Signals
      for neurogranin, a postsynaptic substrate for protein kinase C, were weak or not
      detectable in any regions of either the infant or adult cerebellar cortex. The
      prominent signals for MARCKS mRNA were observed in the deep cerebellar nuclei,
      but signals for both GAP-43 and neurogranin mRNAs were weak or not detectable.
      The prominent signals for both GAP-43 and MARCKS mRNAs were observed in the
      inferior olive, but signals for neurogranin were weak or not detectable. The cell
      type- and region-specific expression of GAP-43 and MARCKS mRNAs in the cerebellum
      may be related to functional specialization regarding plasticity in each type of
      cell and each region of the cerebellum.

PMID- 14595766
TI  - Conserved and convergent organization in the optic lobes of insects and isopods,
      with reference to other crustacean taxa.
AB  - The shared organization of three optic lobe neuropils-the lamina, medulla, and
      lobula-linked by chiasmata has been used to support arguments that insects and
      malacostracans are sister groups. However, in certain insects, the lobula is
      accompanied by a tectum-like fourth neuropil, the lobula plate, characterized by
      wide-field tangential neurons and linked to the medulla by uncrossed axons. The
      identification of a lobula plate in an isopod crustacean raises the question of
      whether the lobula plate of insects and isopods evolved convergently or are
      derived from a common ancestor. This question is here investigated by comparisons
      of insect and crustacean optic lobes. The basal branchiopod crustacean Triops has
      only two visual neuropils and no optic chiasma. This finding contrasts with the
      phyllocarid Nebalia pugettensis, a basal malacostracan whose lamina is linked by
      a chiasma to a medulla that is linked by a second chiasma to a retinotopic
      outswelling of the lateral protocerebrum, called the protolobula. In Nebalia,
      uncrossed axons from the medulla supply a minute fourth optic neuropil.
      Eumalacostracan crustaceans also possess two deep neuropils, one receiving
      crossed axons, the other uncrossed axons. However, in primitive insects, there is
      no separate fourth optic neuropil. Malacostracans and insects also differ in that
      the insect medulla comprises two nested neuropils separated by a layer of axons,
      called the Cuccati bundle. Comparisons suggest that neuroarchitectures of the
      lamina and medulla distal to the Cuccati bundle are equivalent to the
      eumalacostracan lamina and entire medulla. The occurrence of a second optic
      chiasma and protolobula are suggested to be synapomorphic for a
      malacostracan/insect clade.

PMID- 14595767
TI  - Localization of trigeminal, spinal, and reticular neurons involved in the rat
      blink reflex.
AB  - Electrical stimulation of the supraorbital nerve (SO) induces eyelid closure by
      activation of orbicularis oculi muscle motoneurons located in the facial motor
      nucleus (VII). Neurons involved in brainstem central pathways implicated in rat
      blink reflex were localized by analyzing c-Fos protein expression after SO
      stimulation in conjunction with tracing experiments. A retrograde tracer (gold
      horseradish peroxidase [HRP]) was injected into the VII. The distribution
      patterns of activated c-Fos-immunoreactive neurons and of neurons exhibiting both
      c-Fos immunoreactivity and gold-HRP labeling were determined in the sensory
      trigeminal complex (STC), the cervical spinal cord (C1), and the pontomedullary
      reticular formation. Within the STC, c-Fos immunoreactivity labeled neurons in
      the ipsilateral ventral part of the principal nucleus, the pars oralis and
      interpolaris, and bilaterally in the pars caudalis. Colocalization of gold-HRP
      and c-Fos immunoreactivity was observed in neurons of ventral pars caudalis
      layers I-IV and ventral pars interpolaris. In C1, SO stimulation revealed c-Fos
      neurons in laminae I-V. After additional injections in VII, the double-labeled c
      Fos/gold-HRP neurons were concentrated in laminae IV and V. Although c-Fos
      neurons were found throughout the pontomedullary reticular formation, most
      appeared rostrally around the motor trigeminal nucleus and in the ventral
      parvocellular reticular nucleus medial to the fiber bundles of the seventh nerve.
      Caudally, c-Fos neurons were in the lateral portion of the dorsal medullary
      reticular field. In addition, these reticular areas contained double-labeled
      neurons in electrically stimulated rats that had received gold-HRP injections in
      the VII. The presence of double-labeled neurons in the STC, C1, and the reticular
      formation implies that these neurons receive sensory information from eyelids and
      project to the VII. These double-labeled neurons could then be involved in di- or
      trisynaptic pathways contributing to the blink reflex.

PMID- 14595768
TI  - Connections of the posterior thalamic region with the auditory ectosylvian cortex
      in the dog.
AB  - The purpose of the present study was to define auditory cortical areas in the dog
      on the basis of thalamocortical connectivity patterns. Connections between the
      posterior thalamic region and auditory ectosylvian cortex were studied using
      axonally transported tracers: fluorochromes and biotinylated dextran amine. Cyto-
      and chemoarchitecture provided grounds for the division of the posterior thalamic
      region into three complexes, medial geniculate body (MGB), posterior nuclei (Po),
      and lateromedial and suprageniculate nuclei (LM-Sg). Distinctive
      cytoarchitectonic features and the distribution of dominant thalamocortical
      connections (determined quantitatively) allowed us to define four ectosylvian
      areas: middle (EM), anterior (EA), posterior (EP), and composite (CE). We found
      that each area was a place of convergence for projections from five to eleven
      nuclei of the three thalamic complexes, with dominant projections derived from
      one or two nuclei. Dominant topographical projections from the ventral nucleus to
      area EM confirmed physiological reports that it may be considered a primary
      auditory area (AI). We found the anterior part of the EM to be distinct in having
      unique strong connections with the deep dorsal MGB nucleus. Area EA, which
      receives dominant projections from the lateral Po (Pol) and medial MGB nuclei, as
      well as area EP, which receives dominant connections from the dorsal caudal MGB
      nucleus, compose two parasensory areas. Area CE receives dominant projections
      from the extrageniculate nuclei, anterior region of the LM-Sg, and Pol,
      supplemented with an input from the somatosensory VP complex, and may be
      considered a polymodal association area.

PMID- 14595769
TI  - Gap junctions in the inner ear: comparison of distribution patterns in different
      vertebrates and assessement of connexin composition in mammals.
AB  - The distribution and size of gap junctions (GJ) in the sensory epithelia of the
      inner ear have been examined in a reptile (gecko), birds (chicken and owl), and
      mammals (mouse, guinea pig, gerbil, and bat), and the connexin composition of GJs
      in the mammalian inner ear has been assessed. Freeze fracture revealed a common
      pattern of GJ distribution in auditory and vestibular sensory epithelia in the
      different vertebrate classes. In all these tissues, GJs are numerous, often
      occupying more than 25% of the plasma membrane area of supporting cells and
      sometimes composed of more than 100,000 channels. Screening for 12 members of the
      connexin family in the mammalian inner ear by RT-PCR, Western blotting, and
      immunohistochemistry revealed four connexin isotypes, cx26, cx30, cx31, and cx43,
      in the cochlea and three, cx26, cx30, and cx43, in the vestibular organs. With
      antibodies characterised for their specificity, cx26 and cx30 colocalised in
      supporting cells of the organ of Corti, in the basal cell region of the stria
      vascularis, and in type 1 fibrocytes of the spiral ligament. No other connexin
      was detected in these regions. Cx31 was localised among type 2 fibrocytes below
      the spiral prominence, a region where cx30 was not expressed and cx26 expression
      appeared to be low. Cx43 was detected only in the region of "tension fibrocytes"
      lining the inner aspect of the otic capsule. This suggests separate functional
      compartments in the cochlea. In addition to cx26 and cx30, cx43 was detected in
      supporting cells of the vestibular sensory epithelia. Where cx26 and cx30 were
      colocalised, double immunogold labelling of thin sections showed both cx26 and
      cx30 evenly distributed in individual GJ plaques, a pattern consistent with the
      presence of heteromeric connexons. Coimmunoprecipitation of cochlear membrane
      proteins solubilised with a procedure that preserves the oligomeric structure of
      connexons confirmed the presence of heteromeric cx26/cx30 connexons. Heteromeric
      cx26/cx30 connexons may be unique to the inner ear, which could be one factor
      underlying the non-syndromic character of the deafness caused by mutations in
      cx26.

PMID- 14595770
TI  - Evidence that the bed nucleus of the stria terminalis contributes to the
      modulation of hypophysiotropic corticotropin-releasing factor cell responses to
      systemic interleukin-1beta.
AB  - Systemic infection activates the hypothalamic-pituitary-adrenal (HPA) axis, and
      brainstem catecholamine cells have been shown to contribute to this response.
      However, recent work also suggests an important role for the central amygdala
      (CeA). Because direct connections between the CeA and the hypothalamic apex of
      the HPA axis are minimal, the present study investigated whether the bed nucleus
      of the stria terminalis (BNST) might act as a relay between them. This was done
      by using an animal model of acute systemic infection involving intravascular
      delivery of the proinflammatory cytokine interleukin-1beta (IL-1beta, 1
      microg/kg). Unilateral ibotenic acid lesions encompassing the ventral BNST
      significantly reduced both IL-1beta-induced increases in Fos immunoreactivity in
      corticotropin-releasing factor (CRF) cells of the hypothalamic paraventricular
      nucleus (PVN) and corresponding increases in adrenocorticotropic hormone (ACTH)
      secretion. Similar lesions had no effect on CRF cell responses to physical
      restraint, suggesting that the effects of BNST lesions were not due to a
      nonspecific effect on stress responses. In further studies, we examined the
      functional connections between PVN, BNST, and CeA by combining retrograde tracing
      with mapping of IL-1beta-induced increases in Fos in BNST and CeA cells. In the
      case of the BNST, these studies showed that systemic IL-1beta administration
      recruits ventral BNST cells that project directly to the PVN. In the case of the
      CeA, the results obtained were consistent with an arrangement whereby lateral CeA
      cells recruited by systemic IL-1beta could regulate the activity of medial CeA
      cells projecting directly to the BNST. In conclusion, the present findings are
      consistent with the hypothesis that the BNST acts as a relay between the CeA and
      PVN, thereby contributing to CeA modulation of hypophysiotropic CRF cell
      responses to systemic administration of IL-1beta.

PMID- 14595772
TI  - Distribution and development of calretinin-like immunoreactivity in the
      telencephalon of the brown trout, Salmo trutta fario.
AB  - Immunocytochemical techniques were used to investigate the distribution of
      calretinin (CR) in the telencephalon of adult and developing brown trout (Salmo
      trutta fario L.). Previous immunoblotting analysis of trout brain extracts with a
      CR antibody revealed a single protein band of 29 kDa, similar to that observed in
      rat brain extracts. In the forebrain of adult trout, CR immunoreactivity was
      distributed in well-defined cell groups, which allowed us to analyze the CR
      immunoreactive (ir) neuronal populations in terms of their respective regions of
      origin. Our results show that the CR-ir populations of the dorsal and ventral
      telencephalon are differentially distributed along the rostrocaudal axis,
      indicating the existence of four main populations of pallial origin and several
      ventral (subpallial) populations. A highly specific pattern of innervation by CR
      ir fibers of different telencephalic regions was observed from alevins to adults.
      The first CR-ir cell groups of the telencephalic hemispheres were observed in the
      ventral telencephalic area and preoptic region of 7-8-mm embryos. In later
      embryos and in alevins, further CR-ir cell groups appeared in the ventral and
      dorsal telencephalic areas, showing a dorsoventrally banded pattern at
      precommissural levels. Study of CR expression provided new criteria for
      understanding the organization of the telencephalon of trout, and hence of
      teleosts.

PMID- 14595771
TI  - Absence of circadian clock regulation of horizontal cell gap junctional coupling
      reveals two dopamine systems in the goldfish retina.
AB  - In fish and other vertebrate retinas, although dopamine release is regulated by
      both light and an endogenous circadian (24-hour) clock, light increases dopamine
      release to a greater extent than the clock. The clock increases dopamine release
      during the subjective day so that D2-like receptors are activated. It is not
      known, however, whether the retinal clock also activates D1 receptors, which
      display a much lower sensitivity to dopamine in intact tissue. Because activation
      of the D1 receptors on fish cone horizontal (H1) cells uncouples the gap
      junctions between the cells, we studied whether the clock regulates the extent of
      biocytin tracer coupling in the goldfish retina. Tracer coupling between H1 cells
      was extensive under dark-adapted conditions (low scotopic range) and similar in
      the subjective day, subjective night, day, and night. An average of approximately
      180 cells were coupled in each dark-adapted condition. However, bright light
      stimulation or application of the D1 agonist SKF38393 (10 microM) dramatically
      reduced H1 cell coupling. The D2 agonist quinpirole (1 microM) or application of
      the D1 antagonist SCH23390 (10 microM) and/or the D2 antagonist spiperone (10
      microM) had no effect on H1 cell coupling in dark-adapted retinas. These
      observations demonstrate that H1 cell gap junctional coupling and thus D1
      receptor activity are not affected by endogenous dopamine under dark-adapted
      conditions. The results suggest that two different dopamine systems are present
      in the goldfish retina. One system is controlled by an endogenous clock that
      activates low threshold D2-like receptors in the day, whereas the second system
      is controlled by light and involves activation of higher threshold D1 receptors.

PMID- 14595774
TI  - Continuous fermentative hydrogen production from a wheat starch co-product by
      mixed microflora.
AB  - For the transition to the hydrogen economy, hydrogen must be produced
      sustainably, e.g., by the fermentation of agricultural material. Continuous
      fermentative production of hydrogen from an insoluble substrate in nonsterile
      conditions is yet to be reported. In this study hydrogen production using mixed
      microflora from heat-treated digested sewage sludge in nonsterile conditions from
      a particulate co-product of the wheat flour industry (7.5 g L(-1) total hexose)
      at 18- and 12-hour hydraulic retention times, pH 4.5 and 5.2, 30 degrees C and 35
      degrees C was examined. In continuous operation, hydrogen yields of approximately
      1.3 moles hydrogen/mole hexose consumed were obtained, but decreased if acetate
      or propionate levels rose, indicating metabolism shifted towards hydrogen
      consumption by homoacetogenesis or propionate producers. These shifts occurred
      both at pH 4.5 and 5.2. Sparging the reactor with nitrogen to reduce hydrogen in
      the off-gas from 50% to 7% gave stable operation with a hydrogen yield of 1.9
      moles hydrogen /mole hexose consumed over an 18-day period.

PMID- 14595775
TI  - Non-thermal bacterial inactivation with dense CO(2).
AB  - The use of CO(2) under pressure (dense CO(2)) is one of the most promising
      techniques to achieve cold pasteurization and/or sterilization of liquid and
      solid materials, and is likely to replace or partially substitute currently and
      widely applied thermal processes. Although the ability of CO(2) to inactivate
      microorganisms has been known since the 1950's, only within the last 15 years it
      has received special attention, and the scientific and economic interest towards
      practical applications is presently growing more and more. Here we collect and
      discuss the relevant current knowledge about the potentials of dense CO(2) as a
      non-thermal technology in the field of microbial inactivation. We summarize the
      state of the art, including definitions, description of the equipment, relevant
      applications, in both simple suspensions and complex media, for the treatment of
      a wide range of microorganisms in both liquid and solid substrates. Finally, we
      also summarize and discuss the different hypotheses about the mechanisms of
      inactivation.

PMID- 14595776
TI  - Starch fermentation by recombinant saccharomyces cerevisiae strains expressing
      the alpha-amylase and glucoamylase genes from lipomyces kononenkoae and
      saccharomycopsis fibuligera.
AB  - Lipomyces kononenkoae and Saccharomycopsis fibuligera possess highly efficient
      alpha-amylase and/or glucoamylase activities that enable both of these yeasts to
      utilize raw starch as a carbon source. Eight constructs containing the L.
      kononenkoae alpha-amylase genes (LKA1 and LKA2), and the S. fibuligera alpha
      amylase (SFA1) and glucoamylase (SFG1) genes were prepared. The first set of
      constructs comprised four single gene cassettes each containing one of the
      individual amylase coding sequences (LKA1, LKA2, SFA1 or SFG1) under the control
      of the phosphoglycerate kinase gene (PGK1) promoter and terminator, while the
      second set comprised two single cassettes containing SFA1 and SFG1 linked to
      their respective native promoters and terminators. The third set of constructs
      consisted of two double-gene cassettes, one containing LKA1 plus LKA2 under the
      control of the PGK1 promoter and terminator, and the other SFA1 plus SFG1
      controlled by their respective native promoters and terminators. These constructs
      were transformed into a laboratory strain Saccharomyces cerevisiae (Sigma1278b).
      Southern-blot analysis confirmed the stable integration of the different gene
      constructs into the S. cerevisiae genome and plate assays revealed amylolytic
      activity. The strain expressing LKA1 and LKA2 resulted in the highest levels of
      alpha-amylase activity in liquid media. This strain was also the most efficient
      at starch utilization in batch fermentations, utilizing 80% of the available
      starch and producing 0.61g/100 mL of ethanol after 6 days of fermentation. The
      strain expressing SFG1 under the control of the PGK1 expression cassette gave the
      highest levels of glucoamylase activity. It was shown that the co-expression of
      these heterologous alpha-amylase and glucoamylase genes enhance starch
      degradation additively in S. cerevisiae. This study has resulted in progress
      towards laying the foundation for the possible development of efficient starch
      degrading S. cerevisiae strains that could eventually be used in consolidated
      bioprocessing, and in the brewing, whisky, and biofuel industries.

PMID- 14595778
TI  - Expression of vitreoscilla hemoglobin improves growth and levels of extracellular
      enzyme in Yarrowia lipolytica.
AB  - Enhancement in oxygen uptake by high-cell-density cultivations has been achieved
      previously by expression of the bacterial hemoglobin gene from Vitreoscilla. The
      Vitreoscilla hemoglobin (VHb) gene was expressed in the yeast Yarrowia lipolytica
      to study the effect of expression in this commercially important yeast. The
      expression of VHb in this yeast was found to enhance growth, contrary to reported
      observations in wild-type Saccharomyces cerevisiae in which there was no
      significant growth enhancement. VHb-expressing Y. lipolytica exhibited higher
      specific growth rate, enhanced oxygen uptake rate, and higher respiratory
      activity. We report the beneficial effects of VHb expression on growth under
      microaerobic as well as under nonlimiting dissolved oxygen conditions. Earlier
      studies in Y. lipolytica have demonstrated inhibition of mycelia formation by
      respiratory inhibitors and poor nitrogen source, conditions poor for growth.
      VHb(+) Y. lipolytica cells were more efficient at forming mycelia, indicating
      better utilization of available oxygen as compared with the VHb(-) cells.
      Expression of VHb was also found to increase the levels of enzyme ribonuclease
      secreted into the medium, a property that may be beneficial for producing
      heterologous proteins in Y. lipolytica.

PMID- 14595777
TI  - Optknock: a bilevel programming framework for identifying gene knockout
      strategies for microbial strain optimization.
AB  - The advent of genome-scale models of metabolism has laid the foundation for the
      development of computational procedures for suggesting genetic manipulations that
      lead to overproduction. In this work, the computational OptKnock framework is
      introduced for suggesting gene deletion strategies leading to the overproduction
      of chemicals or biochemicals in E. coli. This is accomplished by ensuring that a
      drain towards growth resources (i.e., carbon, redox potential, and energy) must
      be accompanied, due to stoichiometry, by the production of a desired product.
      Computational results for gene deletions for succinate, lactate, and 1,3
      propanediol (PDO) production are in good agreement with mutant strains published
      in the literature. While some of the suggested deletion strategies are
      straightforward and involve eliminating competing reaction pathways, many others
      suggest complex and nonintuitive mechanisms of compensating for the removed
      functionalities. Finally, the OptKnock procedure, by coupling biomass formation
      with chemical production, hints at a growth selection/adaptation system for
      indirectly evolving overproducing mutants.

PMID- 14595779
TI  - Identification of a metabolic network structure representative of Arthrospira
      (spirulina) platensis metabolism.
AB  - A comprehensive network structure for the autotrophic growth of Arthrospira
      platensis is proposed. The metabolic network was built up with 121 reactions and
      134 metabolites including biomass synthesis, production of a growth-associated
      exopolysaccharide, and energy aspects. The model supports the existence of a
      metabolic shunt of PEP to pyruvate through PEP carboxylase, NAD(+)-dependent
      malate dehydrogenase and malic enzyme to convert NADH,H(+) into NADPH,H(+). A
      limit in Arthrospira growth metabolism due to NADH,H(+) balancing is evidenced,
      explaining why the maximal light-dependent mass yield of the growth-associated
      exopolysaccharide was 0.51 kg EPS kg(-1) biomass, consistent with experimental
      results.

PMID- 14595780
TI  - Use of stable emulsion to improve stability, activity, and enantioselectivity of
      lipase immobilized in a membrane reactor.
AB  - The enantiocatalytic performance of immobilized lipase in an emulsion membrane
      reactor using stable emulsion prepared by membrane emulsification technology was
      studied. The production of optical pure (S)-naproxen from racemic naproxen methyl
      ester was used as a model reaction system. The O/W emulsion, containing the
      substrate in the organic phase, was fed to the enzyme membrane reactor from shell
      to-lumen. The enzyme was immobilized in the sponge layer (shell side) of
      capillary polyamide membrane with 50 kDa cut-off. The aqueous phase was able to
      permeate through the membrane while the microemulsion was retained by the thin
      selective layer. Therefore, the substrate was kept in the enzyme-loaded membrane
      while the water-soluble product was continuously removed from the reaction site.
      The results show that lipase maintained stable activity during the entire
      operation time (more than 250 h), showing an enantiomeric excess (96 +/- 2%)
      comparable to the free enzyme (98 +/- 1%) and much higher compared to similar
      lipase-loaded membrane reactors used in two-separate phase systems (90%). The
      results demonstrate that immobilized enzymes can achieve high stability as well
      as high catalytic activity and enantioselectivity.

PMID- 14595781
TI  - Link between primary and secondary metabolism in the biotransformation of
      trimethylammonium compounds by escherichia coli.
AB  - The aim of this work was to understand the steps controlling the process of
      biotransformation of trimethylamonium compounds into L(-)-carnitine by
      Escherichia coli and the link between the central carbon or primary and the
      secondary metabolism expressed. Thus, the enzyme activities involved in the
      biotransformation process of crotonobetaine into L(-)-carnitine (crotonobetaine
      hydration reaction and crotonobetaine reduction reaction), in the synthesis of
      acetyl-CoA (pyruvate dehydrogenase, acetyl-CoA synthetase, and ATP:acetate
      phosphotransferase) and in the distribution of metabolites for the tricarboxylic
      acid (isocitrate dehydrogenase) and glyoxylate (isocitrate lyase) cycles, were
      followed in batch with both growing and resting cells and during continuous cell
      growth in stirred-tank and high-cell-density membrane reactors. In addition, the
      levels of carnitine, crotonobetaine, gamma-butyrobetaine, ATP, NADH/NAD(+), and
      acetyl-CoA/CoA ratios were measured to determine how metabolic fluxes were
      distributed in the catabolic system. The results provide the first experimental
      evidence demonstrating the important role of the glyoxylate shunt during
      biotransformation of resting cells and the need for high levels of ATP to
      maintain metabolite transport and biotransformation (2.1 to 16.0 mmol L
      cellular/mmol ATP L reactor h). Moreover, the results obtained for the pool of
      acetyl-CoA/CoA indicate that it also correlated with the biotransformation
      process. The main metabolic pathway operating during cell growth in the high cell
      density membrane reactor was that related to isocitrate dehydrogenase (during
      start-up) and isocitrate lyase (during steady-state operation), together with
      phosphotransacetylase and acetyl-CoA synthetase. More importantly, the link
      between central carbon and L(-)-carnitine metabolism at the level of the ATP pool
      was also confirmed.

PMID- 14595782
TI  - Data reconciliation and parameter estimation in flux-balance analysis.
AB  - Flux blance analysis (FBA) has been shown to be a very effective tool to
      interpret and predict the metabolism of various microorganisms when the set of
      available measurements is not sufficient to determine the fluxes within the cell.
      In this methodology, an underdetermined stoichiometric model is solved using a
      linear programming (LP) approach. The predictions of FBA models can be improved
      if noisy measurements are checked for consistency, and these in turn are used to
      estimate model parameters. In this work, a formal methodology for data
      reconciliation and parameter estimation with underdetermined stoichiometric
      models is developed and assessed. The procedure is formulated as a nonlinear
      optimization problem, where the LP is transformed into a set of nonlinear
      constraints. However, some of these constraints violate standard regularity
      conditions, making the direct numerical solution very difficult. Hence, a barrier
      formulation is used to represent these constraints, and an iterative procedure is
      defined that allows solving the problem to the desired degree of convergence.
      This methodology is assessed using a stoichiometric yeast model. The procedure is
      used for data reconciliation where more reliable estimations of noisy
      measurements are computed. On the other hand, assuming unknown biomass
      composition, the procedure is applied for simultaneous data reconciliation and
      biomass composition estimation. In both cases it is verified that the f
      measurements required to get unbiased and reliable estimations is reduced if the
      LP approach is included as additional constraints in the optimization.

PMID- 14595783
TI  - Crude aminoacylase from aspergillus sp. is a mixture of hydrolases.
AB  - A range of cross-linked enzyme aggregates (CLEAs) was prepared from commercially
      available aminoacylase I. Results from three test reactions showed that
      aminoacylase does not possess aminolysis or alcoholysis activity, both previously
      ascribed to this enzyme. This result was confirmed using aminoacylase purified by
      chromatographic techniques, which leads us to conclude that the previously
      observed acylations of esters and amines is due to other enzymes present as
      impurities in the crude aminoacylase I.

PMID- 14595784
TI  - Application of multivirus spike approach for viral clearance evaluation.
AB  - Viral contamination is a common risk to continuous cell line-derived biologics.
      Viral validation is thus required for license applications. Viral validation for
      chromatography procedures is routinely performed by spiking a model virus into
      the load material and performing the chromatography procedures at small scale
      under conditions equivalent to the commercial scale. With traditional cell-based
      infectivity assays, one can only spike one model virus at one time. Quantitative
      PCR methods (TaqMan) make it possible to spike multiple model viruses for a
      chromatography procedure simultaneously. TaqMan assays can quantify multiple
      types of viruses and other types of nucleic acid in a single sample without cross
      interference because of its extremely high specificity. Therefore, a multivirus
      spike approach was evaluated and compared to a single virus spike approach. The
      study was further extended to the evaluation of host cell DNA clearance. The data
      shows highly comparable viral and host cell DNA clearance between the single and
      multiple virus spike approaches. Application of a multivirus spike approach
      provides significant time, manpower, and cost savings for new drug development.

PMID- 14595785
TI  - Genetically engineered binding proteins as biosensors for fermentation and cell
      culture.
AB  - The signal-transduction properties and the potential applications of two
      engineered binding proteins from E. coli were extensively studied. Both proteins
      have a single cysteine mutation in their polypeptide chains, which allow the
      introduction of an environmentally sensitive fluorophore: ANS for glucose-binding
      protein (GBP) and acrylodan for glutamine-binding protein (QBP). Both proteins
      respond to their ligands in the micromolar range. The proteins can be stored at 4
      degrees C for at least 5 months. Apparent binding constant, protein
      concentration, and fluorophore are three major factors that affect the
      biosensor's responsive ranges. The binding of the ligand is quick and reversible
      in solution, but the unfavorable dissociation equilibrium and mass-transfer
      resistance for encapsulated proteins can delay the response to several minutes
      and the recovery to hours. Simulated results show that using dialysis tubing with
      a diameter of 1 mm or less is possible to reduce the recovery time to less than
      30 minutes. The potential applications of GBP were studied in yeast fermentation
      and E. coli fermentations in three different scales: 150 mL, 5 mL, and 100
      microL. The results were compared with an YSI 2700 Chemistry Analyzer. Although
      the latter could not give reliable results for the E. coli fermentations as the
      glucose concentration in LB medium is close to its lower detection limit, the
      glucose biosensor presented here was successfully applied to each situation.
      Glutamine-binding protein was tested in cell cultures of two different scales
      (100 mL and 100 microL) and the results were also compared with those obtained
      with YSI. Both QBP and YSI gave good results for the 100-mL cell culture, but the
      relatively large sample volume requirement of YSI (at least 5 microL) prevented
      it from being used in the 100-microL cell culture. Because of their small sample
      volume requirements (less than 1 microL) and high sensitivity, the assays
      described here might find wide applications in high-throughput bioprocessing.

PMID- 14595787
TI  - Cytology turnaround time: are we being too fast?

PMID- 14595786
TI  - Metabolic characteristics of an isocitrate dehydrogenase defective derivative of
      escherichia coli BL21(DE3).
AB  - A 7.8 kb fragment containing isocitrate dehydrogenase (ICDH) gene and its
      flanking regions was cloned from Escherichia coli BL21(DE3) and sequenced. Unlike
      the case of the K-12 strain, the e14 element was not found. The nucleotide
      divergence between these two strains was about 2%. Using the cloned fragment,
      ICDH defective mutant strain, MA1935, was generated from BL21(DE3). Although
      MA1935 accumulated citrate, citrate synthase activity was not repressed but was
      rather high. In addition, isocitrate lyase was not highly induced at the
      stationary phase. MA1935 was shown to be a good host strain for ICDH gene
      expression.

PMID- 14595788
TI  - Histiocytic aggregates in benign nodular goiters mimicking cytologic features of
      papillary thyroid carcinoma (PTC).
AB  - Macrophages/histiocytes are commonly seen in fine-needle aspiration biopsy (FNAB)
      specimens of thyroid nodules with varying degrees of cystic change. In some cases
      the histiocytic component of a cystic thyroid nodule can occur as large tissue
      fragments with marked nuclear atypia, including elongated nuclei with chromatin
      clearing, nuclear grooves, and membrane thickening. These nuclear changes mimic
      cytologic features of papillary thyroid carcinoma (PTC), thus leading to
      diagnostic difficulty in interpretation of FNAB specimens of benign cystic
      thyroid nodules. We evaluated ethanol-fixed Papanicolaou-stained smears of 273
      cases of FNAB thyroid specimens from goitrous nodules with cystic change. Twenty
      cases were selected due to the presence of large aggregates of histiocytic cells
      with the above-mentioned nuclear atypia. An immunostain for histiocytic cells
      using CD68 was performed on alcohol-fixed slides. Histiocytic cells in tissue
      fragments with nuclear atypia mimicking PTC nuclei showed strong cytoplasmic
      staining for CD68; thyroid follicular cells stained negative for CD68. We
      conclude that histiocytic cells in cystic goitrous nodules can show nuclear
      features, which appear similar to PTC nuclei. Immunostaining for CD68 may be of
      value in differentiating between benign cystic thyroid nodules with histiocytic
      aggregates that mimic cytologic features of papillary carcinoma, and PTC with
      cystic change.

PMID- 14595789
TI  - Detection of herpes simplex virus DNA by in situ hybridization technique and
      polymerase chain reaction in Papanicolaou-stained cervicovaginal smears.
AB  - Papanicolaou-stained cervicovaginal smears from six patients with herpes simplex
      virus (HSV) infection were destained and reprocessed by means of in situ
      hybridization (ISH) technique to demonstrate the presence of HSV DNA utilizing
      biotinylated probe. Positive results were obtained in all six cases with intense
      staining signal for the HSV DNA in the nuclei of cells having a ground-glass
      nuclear appearance as well as in multinucleated giant cells. Furthermore, a
      hybridization signal was also noted in smears that had been prepared as much as 3
      yr previously. HSV type 2-specific antigen was confirmed in six destained smears
      by means of immunoperoxidase staining. Moreover, polymerase chain reaction (PCR)
      was also performed for four patients from Pap-destained cervicovaginal smears.
      Amplified HSV DNA was detected in all four cases as 106 basepair PCR products by
      polyacrylamide gel electrophoresis. The combined use of cytology and the ISH
      technique and PCR amplification was of great value for the rapid cytodiagnosis of
      genital infection of HSV.

PMID- 14595790
TI  - Effectiveness of the SurePath liquid-based Pap test in automated screening and in
      detection of HSIL.
AB  - We have shown that SurePath when compared to conventional Paps fails to increase
      HSIL detection. In this study, assessment of test performance characteristics for
      the FocalPoint showed that sensitivity was 96% when manual screening was used as
      the "gold standard." When cervical biopsy, however, was used as the "gold
      standard" FocalPoint sensitivity decreased to 93%, which was the same as manual
      screening. Examination of the FocalPoint "no further review" cases showed that
      4/296 were SIL. To understand better the implication of an SIL diagnosis,
      cervical biopsies generated from SurePath and conventional Paps were compared.
      Conventional Paps diagnosed as LSIL had a biopsy LSIL:HSIL ratio of 3.1/1, while
      SurePath Paps had a biopsy LSIL:HSIL ratio of 1.5/1. These results indicate that
      when cervical biopsy is used as the "gold standard," FocalPoint and manual
      screening of SurePath Paps have similar test performance but that the FocalPoint
      can fail to detect LSIL. Importantly, LSIL in a SurePath Pap is 1.6 times more
      likely to be HSIL on biopsy than LSIL in a conventional Pap.

PMID- 14595791
TI  - Correlation of manual screening and automated (AutoPap 300) analysis of
      conventional cervicovaginal smears with HPV typing using Digene HC II assay.
AB  - Efforts to improve the accuracy and efficacy of diagnosis of cervical cancer and
      its precursor lesions have prompted the development of new technologies,
      including several automated screening systems and human papillomavirus (HPV)
      hybrid capture assay. In this study of 89 conventional cervicovaginal
      (Papanicolaou [Pap]) smears, diagnoses based on manual screening are correlated
      with analyses by the AutoPap 300 primary screening system and results of the
      Digene HPV hybrid capture II assay. We found that (1) the AutoPap system did not
      "miss" (place in the "no further review" category) any of the high-risk HPV DNA
      positive cases, (2) quintile assignments by the AutoPap system did not reliably
      predict the presence or absence of high-risk HPV DNA, (3) cases of low-grade
      squamous intraepithelial lesion (LGSIL) were associated with high-risk rather
      than low-risk HPV genotypes, (4) diagnoses of atypical squamous cells of
      undetermined significance (ASCUS) and above were more frequent in smears from
      patients whose cervicovaginal specimens tested positive rather than negative for
      high-risk HPV DNA (37 of 45 vs 14 of 44) by the Digene HPV hybrid capture II
      assay, and (5) there was a high incidence of high-risk HPV DNA among women whose
      smears did not show cytomorphologic changes of high-grade squamous
      intraepithelial lesion (HGSIL). These findings emphasize that high-risk HPV DNA
      is an indication of risk for HGSIL, not the equivalent for it.

PMID- 14595792
TI  - Sensitive cytologic criteria for the identification of follicular variant of
      papillary thyroid carcinoma in fine-needle aspiration biopsy.
AB  - The cytologic diagnosis of follicular variant of papillary thyroid carcinoma
      (FVPTC) can be extremely challenging and may be associated with false negative
      diagnoses. The purpose of this study was to determine the minimal cytologic
      criteria needed to identify FVPTC. We examined sixty-nine fine-needle aspiration
      (FNA) cases, processed with Diff-Quik and Papanicolaou stains, that were either
      diagnostic or suspicious of FVPTC. All cases had histologic confirmation. These
      cases included 29 FVPTC, 18 classic papillary thyroid carcinoma (PTC), 17
      follicular neoplasm (6 adenomas, 10 carcinomas, 1 neoplasm NOS), 2 lymphocytic
      thyroiditis and 3 nodular goiter. Seven of the most commonly cited
      cytomorphologic features, including flat syncytial sheets, nuclear enlargement,
      fine chromatin, nuclear grooves, nuclear pseudoinclusions, and amount of colloid
      and cytoplasm, were evaluated. A diffuse distribution of fine chromatin, nuclear
      grooves, and colloid was seen more often in FVPTC than in follicular neoplasm
      (p<0.01). The combination of flat/syncytial sheets, nuclear enlargement, and fine
      chromatin was observed in all our cases of FVPTC, and is therefore considered a
      sensitive marker in detecting FVPTC. Logistic regression analysis revealed
      colloid to be the only positive predictor in favor of FVPTC over classic PTC.

PMID- 14595793
TI  - Borderline nuclear change in cervical smears: five-year follow-up.
AB  - Borderline nuclear changes (BNC) account for 5-20% of cervical smears, and their
      outcome is unpredictable. Current management involves repeat smears at 6-mo
      intervals, for a further 12 mo with referral for colposcopy, if the changes
      persist. Given the uncertainty surrounding the natural history of BNC and the
      claim that many patients are further investigated unnecessarily and potentially
      "overtreated," the aim of this study was to determine the outcome for patients
      with a diagnosis of BNC to define whether the management protocol is appropriate
      for this patient group in our laboratory. A total of 808 patients with BNC were
      followed up. There was a 4.05% progression to high-grade dyskaryosis, and most of
      these were detected within the first year of follow-up. This at least justifies
      the early and intense follow-up of this patient group until a reliable "triage
      tool" is adopted to pre-select those patients with BNC who will progress or
      revert to negative.

PMID- 14595794
TI  - Malignant pericardial effusion with metastatic squamous-cell carcinoma:
      discordance between ThinPrep and cell-block cytopreparation.

PMID- 14595795
TI  - Atypical glandular cells--an update.
AB  - The diagnostic category of atypical glandular cells (AGC) in the Bethesda system
      for the reporting of cervicovaginal cytology has undergone significant
      modification since its inception in 1988. More than a decade later, this category
      remains a diagnostic challenge to both clinicians and cytopathologists because of
      the lack of uniform cytologic criteria, the lack of interobserver agreement in
      the diagnosis, and the lack of standardized patient management guidelines. This
      article reviews the current classification of AGC in the Bethesda system, the
      cytomorphologic features and differential diagnosis, the clinical significance of
      a diagnosis of AGC, and the clinical management of patients with AGC. This
      article provides a comprehensive clinicopathologic review of the category of AGC.

PMID- 14595796
TI  - Involvement of the liver by multiple myeloma as nodular lesions: a case diagnosed
      by fine-needle aspiration and immunocytochemistry.
AB  - Liver involvement by multiple myeloma as space-occupying lesions is a rare
      condition with only a few cases reported in the literature. We present a case of
      a 68-year-old man with a prostatic adenocarcinoma who developed a multiple
      myeloma as a second primary malignancy. Hepatic nodules were discovered in the
      tomographic study. Fine-needle aspiration of one of the hepatic lesions showed a
      pleomorphic plasmacytoid tumor. Immunocytochemistry using p63 and kappa-chain
      antibodies was useful in determining the plasmacytic nature of the cells.

PMID- 14595797
TI  - Metastatic ovarian Sertoli-cell tumor: FNA findings with immunohistochemistry.
AB  - A malignant Sertoli cell tumor of the ovary is a rare sex-cord stromal derived
      neoplasm. Sertoli cell tumors account for approximately 4% of Sertoli-stromal
      cell tumors (Hsu et al., J Histochem Cytochem 1981;29:577-580). The diagnosis of
      this entity by fine-needle aspiration and needle core biopsy can be difficult
      when the differential also includes a metastatic renal cell carcinoma, due to the
      overlap of both cytological and histological features. Here, we show that
      immunohistochemical staining on cytological material including alpha-inhibin can
      be used to differentiate between these two malignant tumors.

PMID- 14595798
TI  - Fine-needle aspiration smears from lipomatous hemangiopericytoma need not be
      confused with myxoid liposarcoma.
AB  - Lipomatous hemangiopericytoma (LHPC) is a rare benign soft tissue tumor that may
      mimic soft tissue sarcoma clinically. Despite the fact that LHPC shares most of
      the histologic features with solitary fibrous tumor, it may be occasionally
      misdiagnosed as myxoid liposarcoma or some other type of spindle-cell sarcoma.
      While some studies have addressed the histological features and origin of LHPC,
      no reports of cytological findings have been published. The author describes the
      cytological features of LHPC in two patients with correlations to histological
      and clinical findings. One of aspirates was misdiagnosed as being myxoid
      liposarcoma, while the other one was correctly diagnosed by a combination of FNAB
      and core needle biopsy (CNB). Cytological evaluation of LHPC can be problematic
      due to its rarity and to its similarity with other spindle-cell or fatty tumors.
      Correct diagnosis requires an awareness of cytologic features of this rare tumor
      and the use of ancillary studies.

PMID- 14595799
TI  - Rhabdoid meningioma: intraoperative diagnosis using smear preparation.
AB  - Tumors with rhabdoid morphology were first described by Beckwith and Palmer in
      1978 as aggressive renal tumors in very young children. Subsequently, rhabdoid
      tumors and tumors with rhabdoid features have been described in many other organ
      systems and all tend to have a poor outcome no matter what the histogenesis of
      the original tumor. Rhabdoid cells are plump, with abundant eosinophilic
      fibrillary to hyaline cytoplasm and peripheral, vesicular, variably pleomorphic
      nuclei. Nucleoli are invariably present. While their morphology is well
      recognized in processed biopsy material, their presence on a smear preparation
      can be quite startling. A case is presented to highlight the appearance of
      rhabdoid cells on an intraoperative smear preparation of a rhabdoid meningioma.
      An accompanying secretory component added to the complex picture.

PMID- 14595800
TI  - Rhabdoid meningioma: cytopathologic findings in cerebrospinal fluid.
AB  - Rhabdoid meningioma is a recently described, rare, WHO Grade III intracranial
      tumor with an aggressive growth pattern and increased risk of recurrence. We
      describe the cytopathologic findings on cerebrospinal fluid of one such case in a
      26-yr-old female who underwent resection of a left temporo-parietal mass.
      Cerebrospinal fluid contained abundant malignant cells with a prominent
      "rhabdoid" phenotype, i.e., large cells, eccentric nuclei, single prominent
      nucleoli, and dense eosinophilic cytoplasm. Although rhabdoid meningioma has a
      characteristic cytomorphology, the differential diagnosis of this tumor would
      involve metastatic adenocarcinoma, metastatic malignant melanoma, and other
      tumors with "rhabdoid" features (such as an atypical teratoid/rhabdoid tumor).

PMID- 14595801
TI  - Metastatic lobular mammary carcinoma diagnosed in cervicovaginal smears: a case
      report.
AB  - Lobular carcinoma of the breast uncommonly metastasizes to the cervix. We report
      a case of lobular carcinoma of the breast with an abnormal cervicovaginal smear
      caused by metastasis in the cervix. We also discuss the differential diagnosis of
      primary genital and secondary adenocarcinomas in abnormal cervicovaginal smears.

PMID- 14595802
TI  - Recuse yourself--you're biased!

PMID- 14595803
TI  - Re: Maruta J, et al. Quick aspiration cytology for thyroid nodules by modified
      Ultrafast Papanicolaou staining.

PMID- 14595805
TI  - Protein arrays for autoantibody profiling and fine-specificity mapping.
AB  - Protein arrays provide a powerful approach to study autoimmune disease.
      Autoimmune responses activate B cells to produce autoantibodies that recognize
      self-molecules termed autoantigens, many of which are proteins or protein
      complexes. Protein arrays enable profiling of the specificity of autoantibody
      responses against panels of peptides and proteins representing known autoantigens
      as well as candidate autoantigens. In addition to identifying autoantigens and
      mapping immunodominant epitopes, proteomic analysis of autoantibody responses
      will further enable diagnosis, prognosis, and tailoring of antigen-specific
      tolerizing therapy.

PMID- 14595806
TI  - Signal pathway profiling of ovarian cancer from human tissue specimens using
      reverse-phase protein microarrays.
AB  - Defects in cell signaling pathways play a central role in cancer cell growth,
      survival, invasion and metastasis. An important goal of proteomics is to
      characterize and develop "circuit maps" of these signaling pathways in normal and
      diseased cells. We have used reverse-phase protein array technology coupled with
      laser capture microdissection and phospho-specific antibodies to examine the
      activation status of several key molecular "gates" involved in cell survival and
      proliferation signaling in human ovarian tumor tissue. The levels of activated
      extracellular-regulated kinase (ERK1/2) varied considerably in tumors of the same
      histotype, but no significant differences between histotypes were observed.
      Advanced stage tumors had slightly higher levels of phosphorylated ERK1/2
      compared to early stage tumors. The activation status of Akt and glycogen
      synthase kinase 3beta, key proteins and indicators of the state of the
      phosphatidylinositol 3-kinase/Akt pro-survival pathway also showed more variation
      within each histotype than between the histotypes studied. Our results
      demonstrate the utility of reverse phase protein microarrays for the multiplexed
      analysis of signal transduction from discreet cell populations of cells procured
      directly from human ovarian tumor specimens and suggest that patterns in signal
      pathway activation in ovarian tumors may be patient-specific rather than type or
      stage specific.

PMID- 14595807
TI  - Protein microarrays: molecular profiling technologies for clinical specimens.
AB  - Proteomics, the study of protein function within biologic systems, will further
      our understanding of cancer pathogenesis. Coupled with transcript profiling,
      proteomics can herald the advent of molecular therapy tailored to the individual
      patient's neoplasm. Protein microarrays, one emerging class of proteomic
      technologies, have broad applications for discovery and quantitative analysis.
      This technology is uniquely suited to gather information about the post
      translational modifications of proteins reflecting the activity state of signal
      pathways and networks. Protein microarrays now make it feasible to conduct signal
      network profiling within cellular samples. Nevertheless, to be successful, design
      and use of protein microarrays must take into consideration enormous analytical
      challenges. A subclass of protein microarrays, Reverse Phase Arrays, created to
      meet these challenges, has been optimized for use with tissue specimens, and is
      now in use for the analysis of biopsy samples for clinical trial research.

PMID- 14595808
TI  - Identification of chromatin-related protein interactions using protein
      microarrays.
AB  - Dynamic structural changes in chromatin are mediated by protein interactions that
      modulate multiple cellular processes including replication, transcription,
      recombination and DNA repair. Complexes that recognize chromatin are defined by
      several distinct groups of proteins that either directly modify histones or
      interact with histone-DNA complexes. A protein microarray format was used to
      analyze the interaction of various DNA repair proteins with chromatin components.
      We applied proteins, antibodies and DNA to functionalized glass slides and
      interrogated the slides with our proteins of interest to identify novel protein
      protein interactions for proteins involved in DNA double-strand break repair.
      Here we demonstrate that the DNA repair protein RAD51B, and not its cognate
      partner RAD51C, interacts with histones and not nucleosomes. Nucleosome-specific
      interactions were demonstrated with the recently identified SWI/SNF protein,
      SMARCAL1. Unique RAD51B-histone interactions were corroborated using Far Western
      analysis. This is the first demonstration of an interaction between RAD51B and
      histone proteins that may be important for the successful repair of DNA double
      strand breaks.

PMID- 14595810
TI  - Methods and applications of antibody microarrays in cancer research.
AB  - Antibody microarrays have great potential for significant value in biological
      research. Cancer research in particular could benefit from the unique
      experimental capabilities of this technology. This article examines the current
      state of antibody microarray technological developments and assay formats, along
      with a review of the demonstrated applications to cancer research. Work is
      ongoing in the refinement of various aspects of the protocols and the development
      of robust methods for routine use. Antibody microarray experimental formats can
      be broadly categorized into two classes: (1) direct labeling experiments, and (2)
      dual antibody sandwich assays. In the direct labeling method, the covalent
      labeling of all proteins in a complex mixture provides a means for detecting
      bound proteins after incubation on an antibody microarray. If proteins are
      labeled with a tag, such as biotin, the signal from bound proteins can be
      amplified. In the sandwich assay, proteins captured on an antibody microarray are
      detected by a cocktail of detection antibodies, each antibody matched to one of
      the spotted antibodies. Each format has distinct advantages and disadvantages.
      Several applications of antibody arrays to cancer research have been reported,
      including the analysis of proteins in blood serum, resected frozen tumors, cell
      lines, and on membranes of blood cells. These demonstrations clearly show the
      utility of antibody microarrays for cancer research and signal the imminent
      expansion of this platform to many areas of biological research.

PMID- 14595809
TI  - Molecular profiling of the immune response in colon cancer using protein
      microarrays: occurrence of autoantibodies to ubiquitin C-terminal hydrolase L3.
AB  - We implemented a protein microarray approach to identify proteins that induce a
      humoral response in colon cancer. Solubilized proteins from the LoVo colon
      adenocarcinoma cell line were separated into 1760 fractions, arrayed onto
      nitrocellulose-coated slides, and hybridized with individual sera from 15 newly
      diagnosed patients with colon cancer, 15 with lung cancer, and 15 healthy
      subjects. 39/1760 fractions showed enhanced reactivity with sera from patients
      with colon cancer (p < 0.01) relative to healthy controls. A distinct pattern of
      reactivity was observed with sera from colon cancer relative to lung cancer. One
      fraction that exhibited reactivity with 9/15 colon cancer sera was subjected to
      mass spectrometry leading to the identification of ubiquitin C-terminal hydrolase
      isozyme 3 (UCH-L3) as a constituent. To validate the occurrence of autoantibodies
      to UCH-L3, independent analysis was done by means of Western blots. UCH-L3
      antibodies were detected in 19/43 sera from patients with colon cancer, and in
      0/54 sera from subjects with lung cancer (24), colon adenoma (15) or otherwise
      healthy (15). Our findings indicate the occurrence of an immune response to a
      broad set of antigens in colon cancer and the feasibility of identifying the
      antigenic targets using a combination of protein microarrays and mass
      spectrometry.

PMID- 14595811
TI  - Generation of bioreagents for protein chips.
AB  - Protein microarrays have the potential to dramatically increase the throughput of
      proteomic analysis. Protein expression profiling chips with distinct spots of
      immobilized protein capture agents will allow the simultaneous measurement of
      hundreds to thousands of proteins from one sample. In contrast to DNA chips, for
      which the capture probes are easily designed and synthesized, the development of
      content for protein biochips is a long and laborious process. Careful
      consideration must be given to the specificities desired, the format of the
      assay, and the requirements of the capture agents, as well as to process
      optimization to minimize development time and cost. Monoclonal antibodies have
      been the prime choice as protein capture agents for the majority of protein chips
      developed to date. New technologies for the production of protein capture agents
      are more amenable to automation than traditional monoclonal antibody production
      and therefore carry the promise for industrialization.

PMID- 14595812
TI  - Light directed massively parallel on-chip synthesis of peptide arrays with t-Boc
      chemistry.
AB  - Peptide and peptidomimetic molecule arrays are emerging powerful tools for
      parallel screening of binding in proteomics and pharmaceutical discovery
      research. Up to now the common method of preparing peptide arrays was based on
      spotting on glass using a library of presynthesized peptides. However, due to the
      large number of monomers (amino acids) it is not possible to have combinatorial
      libraries which include all combinations of natural and synthetic amino acids. We
      describe a very flexible on-chip oligopeptide synthesis method which uses the
      well developed t-Boc based solid state synthesis chemistry. A very high degree of
      flexibility is achieved by using light photo generated acids and maskless
      projection lithography for spatially directed deprotection. Use of microfluidic
      chips enables moderately high densities, short reaction times and off-the-shelf
      chemicals. Examples are given from synthesis of metal ion binding peptides and
      epitope binding assays.

PMID- 14595813
TI  - Signal pathway profiling of prostate cancer using reverse phase protein arrays.
AB  - Reverse phase protein arrays represent a new proteomics microarray technology
      with which to study the fluctuating state of the proteome in minute quantities of
      cells. The activation status of cell signaling pathways controls cellular fate
      and deregulation of these pathways underpins carcinogenesis. Changes in pathway
      activation that occur between early stage prostatic epithelial lesions, prostatic
      stroma and the extracellular matrix can be analyzed by obtaining pure populations
      of cell types by laser capture microdissection (LCM) and analyzing the relative
      states of several key phosphorylation points within the cellular circuitry. We
      have applied reverse phase protein array technology to analyze the status of key
      points in cell signaling involved in pro-survival, mitogenic, apoptotic and
      growth regulation pathways in the progression from normal prostate epithelium to
      invasive prostate cancer. Using multiplexed reverse phase protein arrays coupled
      with LCM, the states of signaling changes during disease progression from
      prostate cancer study sets were analyzed. Focused analysis of phospho-specific
      endpoints revealed changes in cellular signaling events through disease
      progression and between patients. We have used a new protein array technology to
      study specific molecular pathways believed to be important in cell survival and
      progression from normal epithelium to invasive carcinoma directly from human
      tissue specimens. With the advent of molecular targeted therapeutics, the
      identification, characterization and monitoring of the signaling events within
      actual human biopsies will be critical for patient-tailored therapy.

PMID- 14595814
TI  - Identification of repertoires of surface antigens on leukemias using an antibody
      microarray.
AB  - We have previously described a microarray of cluster of differentiation (CD)
      antibodies that enables concurrent determination of more than 60 CD antigens on
      leukocytes. This procedure does not require protein purification or labeling, or
      a secondary detection system. Whole cells are captured by a microarray of 10 nL
      antibody dots immobilized on a nitrocellulose film on a microscope slide.
      Distinct patterns of cell binding are observed for different leukemias or
      lymphomas. These haematological malignancies arise from precursor cells of T- or
      B-lymphocytic, or myeloid lineages of hematopoiesis. The dot patterns obtained
      from patients are distinct from those of peripheral blood leukocytes from normal
      subjects. This microarray technology has recently undergone a number of
      refinements. The microarray now contains more CD antibodies, and a scanner for
      imaging dot patterns and software for data analysis provide an extensive
      immunophenotype sufficient for diagnosis of common leukemias. The technology is
      being evaluated for diagnosis of leukemias with parallel use of conventional
      diagnostic criteria.

PMID- 14595815
TI  - Protein microarrays: promising tools for proteomic research.
AB  - Miniaturized and parallelized ligand binding assays are of great interest in
      postgenomic research because microarray technology allows the simultaneous
      determination of a large number of parameters from a minute amount of sample
      within a single experiment. Assay systems based on this technology are used for
      the identification and quantification of proteins as well as for the study of
      protein interactions. Protein affinity assays have been implemented that allow
      the analysis of interactions between proteins with other proteins, peptides, low
      molecular weight compounds, oligosaccharides or DNA. Microarray technology is an
      emerging technology used in global analytical approaches and has a considerable
      impact on proteomic research.

PMID- 14595817
TI  - Current status of protein chip development in terms of fabrication and
      application.
AB  - Sequencing of the human genome revealed that more than 30 000 genes encode
      proteins comprising the human proteome. "Proteomics" can be defined as a field of
      research studying proteins in terms of their function, expression, structure,
      modification and their interaction in physiological and in pathological states.
      The concentration, modification and interaction of proteins in cells, plasma, and
      in tissues are crucial in determining the phenotype of living organisms. Although
      fluctuation of protein concentration is essential to maintain homeostasis,
      protein expression levels are also pathognomonic features. Estimating protein
      concentration by analyzing the quantity of mRNA in cells through conventional
      technologies, such as DNA chips, does not provide precise values since the half
      life and translation efficacy of mRNA is variable. In addition, polypeptides
      undergo post-translational modification. For these reasons, novel techniques are
      needed to analyze multiple proteins simultaneously using protein microarrays. In
      the near future, protein chips may allow construction of complete relational
      databases for metabolic and signal transduction pathways. This article reviews
      the current status of technologies for fabricating protein microarrays and their
      applications.

PMID- 14595816
TI  - Carbohydrate microarrays.
AB  - Sugar chains are abundantly expressed on the outer surfaces of the vast majority
      of viral, bacterial, protozoan and fungal pathogens, as well as on the membranes
      of mammalian cells. This class of carbohydrate molecule is without peer in
      structural diversity and is characteristically suitable for storing and
      displaying biological signals for molecular and cellular recognition. Exploring
      the biological information contained in sugar chains is an important topic of
      current postgenomic research. To facilitate these investigations, we have focused
      on the establishment of a carbohydrate-based microarray technology. Recently, we
      reported that a large panel of carbohydrate-containing macromolecules, including
      polysaccharides, natural glycoconjugates, and the mono- and oligosaccharides
      coupled to carrier molecules, can be stably immobilized on a microglass slide to
      produce a large-scale carbohydrate microarray. In this review, we attempt to
      summarize our recent progress in using this technology to uncover the
      carbohydrate-based biological signals that are recognized by the human and animal
      immune systems. We also discuss the potential of various platforms of
      carbohydrate microarrays that were recently established and analyze the
      challenges to future development of carbohydrate microarray technologies and
      their applications.

PMID- 14595818
TI  - Microarrays to characterize protein interactions on a whole-proteome scale.
AB  - Protein microarrays contain a defined set of proteins spotted and analyzed at
      high density, and can be generally classified into two categories; protein
      profiling arrays and functional protein arrays. Functional protein arrays can be
      made up of any type of protein, and therefore have a diverse set of useful
      applications. Advantages of these arrays include low reagent consumption, rapid
      interpretation of results, and the ability to easily control experimental
      conditions. The ultimate form of a functional protein array consists of all of
      the proteins encoded by the genome of an organism; such an array would be the
      whole proteome equivalent of the whole genome DNA arrays that are now available.
      While proteome microarrays may not have reached the stage of maturity of DNA
      microarrays, recent developments have shown that many of the barriers holding
      back the technology can be overcome. Arrays of this type have already been used
      to rapidly screen large numbers of proteins simultaneously for biochemical
      activities, protein-protein interactions, protein-lipid interactions, protein
      nucleic acid interactions, and protein-small molecule interactions. Eventually,
      functional protein arrays will be used to facilitate various steps in the drug
      discovery and early development processes that are currently bottlenecks in the
      drug development continuum.

PMID- 14595820
TI  - Approaches for the quantification of protein concentration ratios.
AB  - The function of a protein is modulated by its abundance and its degree of
      specific post-translational modifications such as phosphorylation, glycosylation
      or truncation. Consequently, changes of protein concentration and the extent of
      their post-translational modifications has a great influence on the activity of
      intracellular substrate degradation processes, on the activity of intracellular
      biosynthetic pathways, on the cell cycle or on the function of a single cell in a
      whole organism. Defects in this area lead to diseases like cancer or
      neurodegeneration. Therefore, it is a challenge to quantify changes within the
      proteome in the diseased state or between developmental stages and to use the
      results obtained for the maximization of product yields in biotechnology or for
      the development of new drug targets to fight against diseases. In order to
      determine the intracellular concentration of a protein it is necessary to spike
      the cell sample with the same protein in a pure form. If the concentration
      changes of many proteins have to be determined, it takes a long time to obtain
      all these proteins in a pure form. Therefore, most approaches in this field are
      restricted to the determination of protein abundance ratios between two states
      such as diseased or healthy tissues. In this case the proteins in the sample of
      state A function as an internal standard for the proteins in the sample of state
      B and vice versa. The most common techniques in this field are the comparison of
      two-dimensional gel spot intensities after staining or the integration of mass
      spectrometric peak intensities after stable isotope labelling with (13)C, (15)N,
      (18)O or deuterium. The results, advantages and drawbacks of these approaches are
      discussed. Stable isotope labelling in combination with mass spectrometry is more
      accurate than the comparison of spot intensities and has the potential for the
      investigation of highly complex tissue samples.

PMID- 14595819
TI  - Microarrays of tumor cell derived proteins uncover a distinct pattern of prostate
      cancer serum immunoreactivity.
AB  - The broad characterization of the immune responses elicited by tumors has
      valuable applications in diagnostics and basic research. We present here the use
      of microarrays of tumor-derived proteins to profile the antibody repertoire in
      the sera of prostate cancer patients and controls. Two-dimensional liquid
      chromatography was used to separate proteins from the prostate cancer cell line
      LNCaP into 1760 fractions. These fractions were spotted in microarrays on coated
      microscope slides, and the microarrays were incubated individually with serum
      samples from 25 men with prostate cancer and 25 male controls. The amount of
      immunoglobulin bound to each fraction by each serum sample was quantified.
      Statistical analysis revealed that 38 of the fractions had significantly higher
      levels of immunoglobulin binding in the prostate cancer samples compared to the
      controls. Two fractions showed higher binding in the control samples. The
      significantly higher immunoglobulin reactivity from the prostate cancer samples
      may reflect a strong immune response to the tumors in the prostate cancer
      patients. We used multivariate analysis to classify the samples as either
      prostate cancer or control. In a cross-validation study, recursive partitioning
      classified the samples with 84% accuracy. A decision tree with two levels of
      partitioning classified the samples with 98% accuracy. Additional studies will
      allow further characterization of tumor antigens in prostate cancer and their
      significance for diagnosis. These results suggest that microarrays of
      fractionated proteins could be a powerful tool for tumor antigen discovery and
      cancer diagnosis.

PMID- 14595821
TI  - Profiling and imaging proteins in the mouse epididymis by imaging mass
      spectrometry.
AB  - Different aspects of matrix-assisted laser desorption/ionization (MALDI) imaging
      mass spectrometry (IMS) have been used as discovery tools to obtain global and
      time-correlated information on the local proteomic composition of the sexually
      mature mouse epididymis from both qualitative and semiquantitative points of
      view. Tissue sections and laser captured microdissected cells and secretory
      products were analyzed by MALDI-MS and from the recovered protein profiles, over
      400 different proteins were monitored. Over 50 of these, some of which have been
      identified, displayed regionalized behavior from caput to cauda within the
      epididymis. Combining the information obtained from high-resolution imaging mass
      spectrometry and laser captured microdissection experiments, numerous proteins
      were localized within the epididymis at the cellular level. Furthermore, from the
      signal intensities observed in the different protein profiles organized in space,
      semiquantitative information for each protein was obtained.

PMID- 14595822
TI  - Aberrant profiles of native and oxidized glycoproteins in Alzheimer plasma.
AB  - A proteomic approach was employed to elucidate possible differential expression
      of native and oxidized glycoproteins using pooled plasma samples derived from ten
      patients with sporadic Alzheimer's disease (AD) and pooled plasma samples from
      nine normal elderly control (NEC) subjects. The plasma samples were fractionated
      by sequential affinity chromatography on heparin-agarose (HepA) and concanavalin
      A-agarose (ConA) columns followed by separation on one-dimensional and two
      dimensional polyacrylamide gels. Carbonylation (oxidation) of proteins was
      monitored by in-strip derivatization with 2,4-dinitrophenylhydrazine (DNP) and
      anti-DNP immunoblotting. Nine spots representing glycoproteins which showed
      enrichment or high specific oxidation indices in AD HepA-ConA 2-D gels relative
      to NEC samples were analyzed by matrix-assisted laser desorption-time of flight
      mass spectrometry and identified with high probability (p < 0.001) as isoforms of
      human transferrin (Tf), hemopexin (Hpx) and alpha-1-antitrypsin (alpha-1-AT).
      These glycoproteins were concentrated, respectively, 5-, 6.5- and 107-fold in
      HepA-ConA eluates derived from AD plasma relative to the NEC samples. Specific
      oxidation indices of the identified Tf and Hpx isoforms in AD plasma were
      respectively, 7.4 and 2.8 relative to NEC. Our findings provide further evidence
      for systemic derangements in heme/iron/redox homeostasis and activation of the
      acute phase response in sporadic AD. Moreover, the data implicate isoforms of Tf,
      Hpx and alpha-1-AT as potential biological markers of this condition.

PMID- 14595823
TI  - Proteomics of the dissimilatory iron-reducing bacterium Shewanella oneidensis MR
      1, using a matrix-assisted laser desorption/ionization-tandem-time of flight mass
      spectrometer.
AB  - Shewanella oneidensis MR-1 is a gram-negative facultative aerobic bacterium
      living at oxic-anoxic interfaces in nature. The plasticity of terminal electron
      acceptors used under anaerobic conditions is huge, but the adaptation to these
      different environmental conditions remains unclear. In this work, we used a
      proteomic approach to study the protein content when the organism is grown under
      anaerobic respiration conditions on insoluble ferric oxide. By analysis of two
      dimensional gel patterns of soluble protein extracts, we discovered 20
      differentially displayed proteins. The protein spots were further analyzed by
      mass spectrometry for which we used, in addition to nano-high-performance liquid
      chromatography coupled to an electrospray ionization-quadrupole-time of flight
      instrument, a recently introduced matrix-assisted laser desorption/ionization
      (MALDI) tandem-time of flight mass spectrometer. The instrument allows the
      acquisition of high quality spectra, in both the mass spectrometry and tandem
      mass spectrometry mode, and is therefore able to identify protein spots
      unambiguously. Advantageous to electrospray ionization is a minimised sample
      handling, inherent to MALDI ionization, and the presence of high energy
      fragmentation ions, generating sequence information that also can differentiate
      isobaric amino acids. With this strategy, we could point out a regulatory protein
      that is up-regulated under iron(III) respiration. This protein, the aerobic
      respiration control protein (ArcA), has been reported as being a regulator during
      anaerobiosis in other species. To our knowledge, this is the first report of the
      possible involvement of ArcA from S. oneidensis MR-1 in the reduction of ferric
      oxide.

PMID- 14595824
TI  - Proteome analysis of the rat cornea during angiogenesis.
AB  - Angiogenesis is the formation of new blood vessels from the pre-existing
      vasculature. However, the study of this complex process is often hampered by the
      lack of a suitable cell-based model and the tools to study the biochemical events
      that lead to new blood vessel growth. The most widely accepted model for
      angiogenesis is the in vivo rat corneal model. In this model, the cornea, which
      is normally an avascular tissue, is stimulated to undergo angiogenesis in
      response to silver nitrate cauterization or to the implantation of an exogenous
      angiogenic agent. The physical changes associated with the new vessel growth can
      be readily monitored visually, but the regulated biochemical events that result
      in the growth and remodeling of the new vessels are much more challenging to
      decipher. In this report, a proteomics approach is evaluated for its utility in
      deciphering the biochemical events during a time course of angiogenic
      stimulation. At various time points post-silver nitrate cautery, corneas were
      harvested, solubilized, and analyzed by two-dimensional gel electrophoresis.
      Protein expression profiles at the various stages of angiogenesis were compared
      to those of control corneas. One hundred and eleven differentially-expressed
      proteins were identified by either matrix-assisted laser desorption/ionization
      time of flight mass spectrometry or liquid chromatography-coupled electrospray
      ionization tandem mass spectrometry. Many of the proteins up-regulated during the
      angiogenesis process were identified as blood-related proteins, thus validating
      the development of functional blood vessels in the normally avascular tissue of
      the cornea. Furthermore, detection of differentially-regulated proteins in
      cauterized versus control tissue clearly validated the utility of a proteomics
      approach to study this model of angiogenesis. However, in order to get at the key
      regulatory proteins in the angiogenesis process, it is clear that additional
      scale-up and enrichment approaches will be required.

PMID- 14595827
TI  - The emerging field of protein microarrays.

PMID- 14595829
TI  - Synthesis of marine guanidine alkaloids and their application as
      chemical/biological tools.
AB  - Ptilomycalin A and crambescidins, novel marine guanidine alkaloids, have a unique
      pentacyclic guanidine structure, and exhibit a considerable array of biological
      activities. The first method developed for the synthesis of the pentacyclic
      guanidine core structure involved successive 1,3-dipolar cycloaddition reactions
      and resulted in the first total synthesis of crambescidin 359. The synthesis of
      other pentacyclic guanidine derivatives has been based on this methodology and
      applied as tools for studying biological activities, and as chemical reaction
      catalysts.

PMID- 14595830
TI  - Organic supramolecular architectures and their sol-gel transcription to Silica
      nanotubes.
AB  - The design of artificial models of "biomineralization" processes that utilize sol
      gel polymerization has led to a merging of inorganic materials research and
      supramolecular organic chemistry. This article introduces self-assembled
      superstructures of sugar-integrated and crown-appended cholesterol gelators,
      which are used as versatile building blocks in organogels and as templates for
      sol-gel transcription. This article focuses on the use of self-assembled organic
      superstructures in the creation of novel inorganic materials with controlled
      morphologies.

PMID- 14595831
TI  - Directly linked porphyrin arrays.
AB  - The Ag(I)-promoted oxidative meso-meso coupling reaction of 5,15-diaryl Zn(II)
      porphyrin was serendipitously found in the course of our synthetic approaches
      towards photosynthetic reaction centers. Based on this reaction, a variety of
      directly linked and fused porphyrin arrays have been synthesized, including
      linear meso-meso-linked porphyrin arrays, windmill- and grid-shaped porphyrin
      arrays, meso-beta singly linked diporphyrins, beta-beta linked diporphyrins, meso
      beta doubly linked (fused) diporphyrins and oligoporphyrins, meso-meso beta-beta
      doubly linked (fused) diporphyrins, and meso-meso beta-beta-beta-beta triply
      linked (fused) diporphyrins. The meso-meso coupling reaction of 5,15-diaryl
      Zn(II)-porphyrins is advantageous considering its high regioselectivity as well
      as its ease of extension to large porphyrin arrays as is demonstrated by the
      synthesis of a discrete meso-meso-linked 128-mer and poly(5,15-porphyrinylene).
      Finally, the oxidation of end-phenyl capped meso-meso-linked zinc porphyrins with
      DDQ-Sc(OTf)(3) gave pi-conjugated flat porphyrin tapes. To the best of our
      knowledge, the meso-meso linked 128-mer is the longest man-made discrete
      molecule, and the porphyrin tape 12-mer is the most extensively conjugated
      porphyrin array, as evinced by the lowest electronic band peak at 3500 cm(-1).

PMID- 14595832
TI  - The repetitive C-terminal domain of RNA polymerase II: multiple conformational
      states drive the transcription cycle.
AB  - RNA polymerase (RNAP) II is a complex multisubunit enzyme responsible for the
      synthesis of mRNA in eukaryotic cells. The largest subunit contains at its C
      terminus a unique domain, designated the CTD, comprised of tandem repeats of the
      consensus sequence Tyr(1)Ser(2)Pro(3)Thr(4)Ser(5)Pro(6)Ser(7). This repeat occurs
      52 times in mammalian RNAP II. The CTD is subject to extensive phosphorylation at
      specific points in the transcription cycle by distinct CTD kinases that
      phosphorylate certain positions within the consensus repeat. The level and
      pattern of phosphorylation is determined by the concerted action of CTD kinases
      and CTD phosphatases. The highly dynamic modification by multiple CTD kinases and
      phosphatases generate distinct conformations of the CTD that facilitate the
      recruitment of specific macromolecular assemblies to RNAP II. These CTD
      interacting proteins influence formation of a preinitiation complex at the
      promoter and couple processing of the primary transcript to the elongation
      complex.

PMID- 14595833
TI  - Proximal upstream region of zebrafish bone morphogenetic protein 4 promoter
      directs heart expression of green fluorescent protein.
AB  - We examined the activity of the bone morphogenetic protein 4 (BMP4) promoter in
      zebrafish embryos via transient and stable transgenic expression analyses in
      order to obtain a better understanding of the regulation of BMP4 tissue-specific
      expression. Transient expression studies showed that the 9.0-kb BMP4
      promoter/upstream region drove green fluorescent protein (GFP) expression mainly
      in the heart. Deletion analyses indicated the existence of multiple regulatory
      elements in the 7.5-kb BMP4 promoter/proximal upstream region. In addition, a
      coinjection experiment further demonstrated the 2.4-kb Bgl II-Hind III DNA region
      contains major positive regulatory elements. In addition, stable transgenic lines
      were established to further confirm the heart-specificity of this segment in BMP4
      promoter. The results showed that GFP was mainly localized in the myocardium of
      developing ventricles of 48-hpf (hours postfertilization), 72-hpf, and 100-hpf
      transgenic F(1) embryos. Together, these results indicate that the 7.5-kb BMP4
      promoter/proximal upstream region specifically contains regulatory elements for
      BMP4 expression in the heart, while regulatory elements for other endogenous BMP4
      expressing tissues may reside in more distal regions and/or in introns.

PMID- 14595834
TI  - Differential requirements for the neurogenic gene almondex during Drosophila
      melanogaster development.
AB  - During early development, the neurogenic genes of Drosophila melanogaster are
      involved in the control of cell fates in the neurectoderm; almondex (amx) belongs
      to this category of genes. We have identified the amx locus and rescued the amx
      embryonic neurogenic phenotype with a 1.5 kb DNA fragment. Using a small
      deficiency, we generated a new amx mutant background called amx(m), which is a
      null allele. Besides the characteristic neurogenic maternal effect caused by loss
      of amx, amx(m) flies display a new imaginal phenotype resembling loss of function
      of Notch. We describe amx-induced misregulation of the Notch pathway target
      E(spl) m7 in embryos and genetic interactions between amx and Notch pathway
      mutants in adult flies. These data show that wildtype amx acts as a novel
      positive regulator of the Notch pathway and is required at different levels
      during development.

PMID- 14595835
TI  - Pbx1 is essential for adrenal development and urogenital differentiation.
AB  - Pbx1 encodes a TALE (three amino acid loop extension) class homeodomain protein
      that participates in multimeric transcriptional complexes to regulate
      developmental gene expression. Previous studies demonstrate a critical role for
      Pbx1 as a developmental regulator whose absence results in embryonic lethality
      and multiple tissue and organ system abnormalities. Here we report a requirement
      for Pbx1 in the differentiation of urogenital organs, where Pbx1 is widely
      expressed in mesenchymal tissues. The complete lack of adrenal glands and
      formation of gonads displaying rudimentary sexual differentiation correlated with
      decreased cellular proliferation in Pbx1(-/-) genital ridges. Furthermore,
      expression of steroidogenic factor-1 (SF-1), a nuclear receptor essential for
      adrenal organogenesis, was reduced to minimal levels in Pbx1 mutants, indicating
      an upstream function for Pbx1 in adrenocortical development. Finally, loss of
      Pbx1 markedly reduces urogenital ridge outgrowth and results in impaired
      differentiation of the mesonephros and kidneys and the absence of Mullerian
      ducts. These findings establish a Pbx1-dependent pathway that regulates the
      expansion of SF-1 positive cells essential for adrenal formation and gonadal
      differentiation and demonstrate an early requirement for Pbx1 in urogenital
      development.

PMID- 14595836
TI  - Tyrosinase-Cre mice for tissue-specific gene ablation in neural crest and
      neuroepithelial-derived tissues.
AB  - This study describes the derivation of two new lines of transgenic mice that
      express Cre recombinase under the control of tyrosinase transcriptional elements.
      To determine the suitability of the Tyrosinase-Cre transgene for tissue-specific
      gene ablation studies, a fate map of Cre expression domains was determined using
      the Z/AP reporter strain. It was shown that Cre-expressing cells contribute to a
      wide array of neural crest and neuroepithelial-derived lineages. The melanocytes
      of the harderian gland and eye choroid, sympathetic cephalic ganglia,
      leptomeninges of the telencephalon, as well as cranial nerves (V), (VII), and
      (IX) are derived either fully or partly from Cre-expressing cephalic crest. The
      cells contributing to the cranial nerves were the first to exhibit Cre expression
      at E10.5 as they were migrating into the branchial arches. The melanocytes,
      chromaffin cells of the adrenal medulla, and dorsal root ganglia are derived from
      trunk neural crest that either express Cre or were derived from Cre-expressing
      precursors. An array of brain tissue including the basal forebrain, hippocampus,
      olfactory bulb, and the granule cell layer of the lateral cerebellum, as well as
      the retinal pigmented epithelium and glia of the optic nerve originate from Cre
      expressing neuroepithelial cells.

PMID- 14595837
TI  - Characterization of Notch3-deficient mice: normal embryonic development and
      absence of genetic interactions with a Notch1 mutation.
AB  - The Notch signaling pathway is an evolutionarily conserved signaling mechanism
      and mutations in its components disrupt cell fate specification and embryonic
      development in many organisms. To analyze the in vivo role of the Notch3 gene in
      mice, we created a deletion allele by gene targeting. Embryos homozygous for this
      mutation developed normally and homozygous mutant adults were viable and fertile.
      We also examined whether we could detect genetic interactions during early
      embryogenesis between the Notch3 mutation and a targeted mutation of the Notch1
      gene. Double homozygous mutant embryos exhibited defects normally observed in
      Notch1-deficient embryos, but we detected no obvious synergistic effects in the
      double mutants. These data demonstrate that the Notch3 gene is not essential for
      embryonic development or fertility in mice, and does not have a redundant
      function with the Notch1 gene during early embryogenesis.

PMID- 14595838
TI  - Cardiac electrophysiological phenotypes in postnatal expression of Nkx2.5
      transgenic mice.
AB  - Nkx2.5 is a conserved homeodomain (HD) containing a transcription factor
      essential for early cardiac development. We generated several mutations modeling
      some patients with congenital heart disease. Transgenic mice (tg) expressing the
      wildtype Nkx2.5 under beta-myosin heavy chain (MHC) promoter died during the
      embryonic stage. However, tg mice expressing this mutation under beta-MHC
      promoter (beta-MHC-TG(I183P)), the wildtype Nkx2.5 (alpha-MHC-TG(wild)), and a
      putative transcriptionally active mutant (carboxyl-terminus deletion, alpha-MHC
      TG(DeltaC)) under alpha-MHC promoter showed postnatal lethal heart failure. Given
      the profound atrioventricular conduction abnormalities we recently demonstrated
      in beta-MHC-TG(I183P) mice, the aim of this study was to determine whether alpha
      MHC-TG(wild) and alpha-MHC-TG(DeltaC) mutant mice display similar cardiac
      electrophysiological phenotypes. Surface ECG recordings and in vivo
      electrophysiology studies were performed in alpha-MHC-TG(wild) mice and controls
      at 6 weeks of age, and in alpha-MHC-TG(DeltaC) mice and controls at 10 weeks of
      age. Ambulatory ECG recordings in alpha-MHC-TG(wild) and controls were obtained
      using an implantable radiofrequency telemetry system. PR prolongation and
      atrioventricular nodal dysfunction were detected in alpha-MHC-TG(wild) and alpha
      MHC-TG(DeltaC) mice. Bradycardia and prolonged PR interval were seen in
      ambulatory ECG of alpha-MHC-TG(wild) mice compared to controls. Several alpha-MHC
      TG(wild) mice died of bradycardia. Fetal and neonatal mutant Nkx2.5 expression
      causes severe cardiac conduction failure. Postnatal overexpression of nonmutant
      (wild) Nkx2.5 also causes conduction abnormalities, although the onset is after
      the neonatal stage. Bradycardia and AV conduction failure may contribute to the
      lethal heart failure and early mortality.

PMID- 14595839
TI  - Maternal inheritance of Cre activity in a Sox2Cre deleter strain.
AB  - The Sox2 gene is expressed in several undifferentiated cell types. In an earlier
      study we described a Sox2Cre transgene that mediates epiblast-specific Cre
      mediated modification of gene activity in the embryo. Here we report that this
      transgene is active in the female germline. Consequently, all offspring that
      arise from female mice heterozygous for the Sox2Cre transgene have demonstrable
      Cre activity irrespective of whether they inherit the transgene itself. Maternal
      inheritance of Cre activity allows the efficient modification of gene activity
      for functional analysis.

PMID- 14595840
TI  - Highly efficient transgene-independent recombination directed by a maternally
      derived SOX2CRE transgene.
AB  - The Cre/loxP site-specific recombination system is a powerful tool that allows
      gene inactivation in a tissue- and time-specific manner. Several reports have
      shown that the Sox2Cre transgenic strain provides a very efficient means to
      delete gene function from the early epiblast (Hayashi et al.: Gene Expr Patterns
      2:93-97, 2002; Vincent et al.: Genes Dev 17:1646-1662, 2003). Routinely, male
      studs carrying one null allele of the gene of interest and the Cre transgene are
      crossed to females homozygous for the conditional allele. Normally, excision is
      observed only in the progeny inheriting both the Cre transgene and the
      conditional allele. Here we report that when the Sox2Cre transgene is inherited
      maternally, excision occurs in all offspring irrespective of whether they carry
      the Cre transgene. Thus, Sox2Cre females provide a generally useful tool for
      rapid and efficient removal of loxP flanked sequences in vivo.

PMID- 14595841
TI  - RNA amplification and transcriptional profiling for analysis of stem cell
      populations.
AB  - As stem cells constitute a rare cell pool, a global analysis of gene expression
      is typically not possible. Here, we use a T7-based RNA amplification method
      combined with high-density oligonucleotide array technology to analyze gene
      expression. We isolated RNA from ES cells (100-100,000 cells), subjected them to
      two rounds of amplification, and compared each sample using microarray analysis.
      RNA isolation and amplification was highly reproducible and sensitive for the
      analysis of low abundant transcripts. Greater than 93% of the transcripts
      expressed were changed less than 2-fold when comparing the results of amplified
      RNA (100 cells to 100,000 cells) to unamplified RNA (isolated from 1,000,000
      cells). This transcriptional analysis resulted in minimal skewing of gene
      expression. Using this technology, we analyzed the genetic programs of ES cells,
      STO feeder cells, and adult cardiomyocytes. We conclude that these technologies
      can be applied to the analysis of the genetic programs of rare cell populations
      and ultimately this analysis will enhance our understanding of the regulatory
      mechanisms of stem cell populations.

PMID- 14595842
TI  - Assessing the contributions of gene products to the form-shaping events of
      neurulation: a transgenic approach in chick.
AB  - Most of our current knowledge on the tissue and cellular basis of neurulation in
      amniotes has been gained using the chick embryo as an experimental model system.
      Gene manipulation during chick neurulation has been difficult, greatly limiting
      our ability to assess the contribution of gene products to the tissue and
      cellular behaviors of neurulation. Using electroporation, we have developed a
      simple and reliable method for expressing transgenes in the ectoderm of the
      neural folds of chick embryos developing in whole-embryo culture. Sense- or
      antisense-expressing plasmids are electroporated, resulting in gain or loss of
      gene function, respectively. The morphogenesis of transgenic tissues was compared
      to the morphogenesis of contralateral wildtype tissues as neurulation was taking
      place. As a proof of principle, we present a functional analysis of the chick
      gene encoding Cartilage Linking Protein 1 (CRTL1), identified as a candidate
      neurulation gene using subtractive hybridization. This experimental approach
      provides a much-needed innovation for studying the mechanisms by which genes
      influence neurulation and reveals here important contributions of CRTL1 to the
      formation of the neural folds.

PMID- 14595843
TI  - Analysis of a null mutation in the Drosophila splicing regulator Tra2 suggests
      its function is restricted to sexual differentiation.
AB  - Tra2 is a regulator of pre-mRNA splicing and a key component of the Drosophila
      somatic sex determination pathway. Functional orthologs of this protein are
      thought to perform nonsex-specific functions essential for viability in both
      vertebrates and nematodes. Although Drosophila Tra2 is expressed throughout the
      soma of both sexes, studies on it have focused only on the sex-specific
      phenotypes of known viable alleles. Here we show that that widely used tra2
      mutant alleles have residual activity and are not suitable for evaluating its
      effect on viability. To test whether Tra2 has an essential role in development,
      we generated a transposon-induced deletion in critical coding sequences. We find
      that tra2 deletion adults can survive as well as their heterozygous siblings.
      Thus, in contrast to other organisms, Tra2 is not required in Drosophila for
      general viability under laboratory conditions.

PMID- 14595844
TI  - Subtractive hybridisation screen identifies sexually dimorphic gene expression in
      the embryonic mouse gonad.
AB  - The sex of most mammals is determined by the action of SRY. Its presence
      initiates testis formation resulting in male differentiation, its absence results
      in ovary formation and female differentiation. We have used suppression
      subtraction hybridisation between 12.0-12.5 days postcoitum (dpc) mouse testes
      and ovaries to identify genes that potentially lie within the Sry pathway.
      Normalised urogenital ridge libraries comprising 8,352 clones were differentially
      screened with subtracted probes. A total of 272 candidate cDNAs were tested for
      qualitative differential expression and localisation by whole mount in situ
      hybridisation; germ cell-dependent or -independent expression was further
      resolved using busulfan. Fifty-four genes were identified that showed higher
      expression in the testis than the ovary. One novel gene may be a candidate for
      interactions with WT1, based on its localisation to Sertoli cells and map
      position (16q24.3).

PMID- 14595845
TI  - Microbubble-enhanced sonoporation: efficient gene transduction technique for
      chick embryos.
AB  - The gene transduction technique is a useful method to study gene functions that
      underlie vertebrate embryogenesis. In this study, a new gene transduction
      technique is reported using microbubble-enhanced sonoporation (hereafter referred
      to as sonoporation) to achieve ectopic and transient gene expression for several
      embryonic organs including embryonic chick limb bud mesenchymes. The technique
      proposed in this study has the advantages of 1) relatively simple gene
      transduction procedures, and 2) efficient exogenous gene transduction and
      expression with lower damages to embryos. Green fluorescent protein (GFP) or LacZ
      was misexpressed in limb bud mesenchymes by sonoporation, with the introduced
      expression transiently detected in the injected sites. Most of the transduced
      chick embryos survived without showing significant embryonic abnormalities or
      cell death after sonoporation. To demonstrate its efficacy for assessing the
      effect of transient gene transduction, the Shh (sonic hedgehog) was transduced
      into the developing chick limb bud. The transduced limb bud displayed limb
      malformations including partial digit duplication. Advantages and possible future
      applications in relation to this method are discussed.

PMID- 14595846
TI  - Heat shock response: hsp70 in environmental monitoring.
AB  - Heat shock proteins (Hsps) are a ubiquitous feature of cells in which these
      proteins cope with stress-induced denaturation of other proteins. Among the
      different families of Hsps, the 70 kDa family (hsp70) is the most highly
      conserved and has been most extensively studied. Apart from their primary role in
      cellular defense under stress condition, a number of studies in recent years have
      shown the immense potential of hsp70 in pollution monitoring using even
      transgenic approach both in vivo and in vitro. This article reviews the recent
      developments in the widespread application of hsp70 in environmental risk
      assessment.

PMID- 14595847
TI  - Two cinnamate derivatives produce similar alteration in mRNA expression and
      activity of antioxidant enzymes in rats.
AB  - Cinnamate is a widespread secondary metabolite of phenolic compound synthesized
      by plants for defensive purposes. The current study was designed to investigate
      the effect of two structurally related cinnamate derivatives, 4-hydroxycinnamate
      and 3-(4-hydroxyphenyl)propionic acid (HPP), on the mRNA expression and activity
      of antioxidant enzymes in high-cholesterol-fed rats. Male rats were fed a 1 g/100
      g high-cholesterol diet with supplements of either 4-hydroxycinnamate or HPP
      (0.135 mmol/100 g diet) for 6 weeks. The plasma paraoxonase activity was found to
      be higher in the cinnamate-derivative-supplemented groups than in the control
      group. The erythrocyte superoxide dismutase (SOD) and catalase (CAT) activities,
      plus glutathione (GSH) level, were all significantly higher in the 4
      hydroxycinnamate- and HPP-supplemented groups than in the control group. However,
      both 4-hydroxycinnamate and HPP supplementation significantly lowered the hepatic
      activities and mRNA expression of CAT and glutathione peroxidase (GSH-Px)
      compared to the control group. The hepatic mRNA expression and activity of SOD
      did not differ between the groups. The hepatic thiobarbituric acid reactive
      substances (TBARS) level was significantly lowered by the 4-hydroxycinnamate and
      HPP supplementation. Accordingly, these results indicate that supplementation by
      4-hydroxycinnamate and HPP would seem to enhance the antioxidative defense of
      erythrocyte. Both HPP and 4-hydroxycinnamate would appear to be beneficial in
      improving the function of antioxidative enzymes on a molecular level in high
      cholesterol-fed rats.

PMID- 14595848
TI  - Altered expression of transcripts for alpha-tubulin and an unidentified gene in
      the spinal cord of phenyl saligenin phosphate treated hens (Gallus gallus).
AB  - Phenyl saligenin phosphate (PSP) induces a central-peripheral distal axonopathy
      in domestic fowl that develops 7-21 days after a single exposure. Neurotoxic
      esterase (NTE) is the initial molecular target for this neurotoxicity. PSP has to
      covalently bind to NTE and chemically "age" for induction of axonopathy. It was
      hypothesized that exposure to PSP results in early changes in spinal cord gene
      expression that do not occur with phenylmethylsulfonyl fluoride, a non
      neuropathic compound that also inhibits NTE, or DMSO controls. Targeted display
      was used to screen approximately 15,000 gel bands. Three candidate genes were
      identified, but only the transcript designated P1 showed decreased expression
      following PSP exposure (2 mg/kg i.m.) in subsequent Northern blot and in situ
      hybridization experiments in samples taken <48 h after exposure. Additional
      experiments revealed that a approximately 2.5 kb alpha-tubulin transcript had
      decreased expression at 12-48 h after PSP exposure, with maximum change at 48 h
      (33%, p = 0.0479). A approximately 4.5 kb alpha-tubulin transcript had increased
      expression at 12 h (38%, p = 0.0125) and decreased expression at 48 h (28%, p =
      0.0576). In situ hybridization on spinal cord revealed neuronal expression of P1
      and alpha-tubulin transcripts. Decreased expression of transcripts for P1 and
      alpha-tubulin was present at 12 and 48 h, respectively. This decrease occurred in
      all neurons, not just those whose axons degenerate. Results suggest that (1) in
      PSP-induced OPIDN (organophosphorus-induced delayed neurotoxicity) some gene
      transcript expression changes are associated with initiation of axonopathy, and
      (2) PSP modulates spinal cord gene expression in neuronal types that do not
      undergo axonal degeneration.

PMID- 14595850
TI  - Perinatal exposure to low doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin alters sex
      dependent expression of hepatic CYP2C11.
AB  - The cytochrome P450 (CYP) isoform CYP2C11 is specifically expressed in the liver
      of adult male rats, and 5alpha-reductase is specifically expressed in the liver
      of the adult female rats. The sexually dimorphic expressions of these hepatic
      enzymes are regulated by the sex-dependent profiles of the circulating growth
      hormone (GH). However, it is not well known whether hormonal imprinting or
      activation factors in the neonatal brain influence the sexually dimorphic
      expression patterns of hepatic enzymes. We therefore examined the effect of
      perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on sex-dependent
      expressions of hepatic enzymes. Pregnant rats were treated with TCDD at a dose of
      0, 200, or 800 ng/kg on gestation day 15, exposing the pups to the chemical.
      Although the expression of CYP2C11 protein in the livers of male pups on
      postnatal day (PND) 49 was significantly higher than that of the controls, but
      the 5alpha-reductase activities in the livers of female pups were not altered by
      exposure to TCDD. Focusing on perinatal periods, testosterone and estrogen levels
      significantly increased in the brain of male pups on PND 2. The results suggest
      that the alteration of testosterone and estrogen levels affect hormonal
      imprinting in the neonatal brain of male pups, and thus induces a change in the
      level of male-specific hepatic CYP2C11. We conclude that perinatal exposure to
      TCDD at low doses may change the sexual differentiation of the neonatal brain in
      male rats.

PMID- 14595849
TI  - Effects of endocrine disrupting chemicals on distinct expression patterns of
      estrogen receptor, cytochrome P450 aromatase and p53 genes in oryzias latipes
      liver.
AB  - Expression pattern analysis of three genes, i.e., the estrogen receptor (ER),
      cytochrome P450 aromatase (CYP19), and p53 genes, in Japanese Medaka liver was
      studied in the presence of 17beta-estradiol, nonylphenol, and bisphenol A. Using
      the distinct expression patterns of these three genes, the different
      transcriptional mechanisms by endocrine disrupting chemicals (EDCs), and the
      stability of the transcripts of each gene, were examined. In tests done with both
      male and female Medaka over 10 days, it was found that each gene had a specific
      expression pattern. The expression of the ER gene increased rapidly for the first
      2 days and then leveled out and maintained a stable expression level, while the
      CYP19 gene expression showed a fairly consistent increase in the expression
      levels after exposure. In contrast to both these genes, the p53 gene expression
      levels reached a maximum value within 2 days and then gradually decreased for the
      remainder of the experiment. These findings suggest that different expression
      mechanisms may exist for these genes in Japanese Medaka in response to the
      presence of EDCs.

PMID- 14595851
TI  - Naphthalene exposure: effects on gene expression and proliferation in human cord
      blood cells.
AB  - In this study, the effect of naphthalene on the induction of apoptosis and gene
      expression profiles in cord blood cells has been evaluated, as well as its
      activity on the BCL-2 related protein expression. After 6, 24, and 48 h of
      exposure to naphthalene (500 microM), a decrease in cell death was observed: the
      cells became more resistant to the toxicant and capable of surviving after the
      treatment. A Western blot analysis revealed an overexpression of BCL-2, c-JUN, c
      FOS, and RAF-1 proteins, which are involved in the antiapoptotic response and in
      the regulation of cell growth, differentiation, and development. Furthermore,
      macroarray analysis showed that naphthalene modified cord blood gene expression,
      inducing IL-8 precursor and T-cell transcription factor and decreasing the level
      of RNA-binding protein FUS/TLS.

PMID- 14595853
TI  - Entropy evaluation using the kinetic method: is it feasible?
AB  - The kinetic method is one of the most widely used experimental techniques for the
      measurement of thermochemical parameters by mass spectrometry. Recently it has
      been realized that it can also be used to determine reaction entropies, but the
      validity of this approach has not been established. This Perspective evaluates
      kinetic method plots in cases where there is a significant entropy difference
      between the competing fragmentation channels (i.e. between sample and reference
      compounds in the dissociating cluster ion). The concept underlying this study is
      to calculate mass spectra theoretically, based on known thermochemical parameters
      and as a function of experimental conditions. This can be done accurately using
      the RRKM-based MassKinetics software. The resulting mass spectra are then
      interpreted by the kinetic method, yielding DeltaH and DeltaS values. These
      values are, in turn, compared with the true values used to generate the
      calculated mass spectra. The results show that the reaction entropy difference
      between sample and reference has a very large influence on kinetic method plots.
      This should always be considered when studying energy-dependent mass spectra
      (using metastable ions or low- or high-energy collision-induced dissociation
      (CID)), even if only DeltaH is to be determined. Kinetic method plots are not
      strictly linear and this becomes a serious issue in the case of small molecules
      showing a large entropy effect. In such cases, results obtained at a low degree
      of excitation are more accurate. Energy and entropy effects can be evaluated in a
      relatively straightforward manner: first, the apparent Gibbs energy (DeltaG(app))
      and effective temperature (T(eff)) are determined from kinetic method plots
      (intercept and slope, respectively), obtained from experiments using various
      degrees of excitation. Second, the resulting DeltaG(app) is plotted against
      T(eff), the slope yielding DeltaS while the intercept (extrapolation to zero
      temperature) yields DeltaH. This data evaluation yields more accurate results
      than alternative methods used in the literature. The resulting DeltaH values are
      fairly accurate, with errors, in most cases, <4 kJ mol(-1). On the other hand,
      DeltaS is systematically underestimated by 20-40%. Empirically scaling DeltaS
      values determined by the kinetic method by 1.35 results in a DeltaS value within
      20% (or 10 J mol(-1) K(-1)) of the theoretical value.

PMID- 14595852
TI  - Effect of oxalomalate on lipid metabolism and antioxidant defense system in rats.
AB  - The metabolic functions of NADP(+)-specific isocitrate dehydrogenase (ID2), which
      may participate in the production of NADPH and biosynthesis of fatty acids, are
      not yet clearly understood. Accordingly, the current study investigated the
      effect of oxalomalate, known as a competitive inhibitor of ID2 in vitro, on lipid
      metabolism and the cellular defense system in vivo. Male Sprague Dawley rats (3
      weeks old) were divided into two groups, fed a pelletized AIN-76 semisynthetic
      diet for 8 weeks, and injected intraperioneally with either saline or oxalomalate
      (25 mg/kg BW) dissolved in saline every 2 days. Oxalomalate did not lower the
      body weight and adipose tissue weight significantly; however, it significantly
      lower the plasma leptin concentration (p < 0.000), plasma and hepatic
      triglyceride levels (p < 0.01, p < 0.05), and adipocyte lipoprotein lipase
      activity (p < 0.01) compared to the control group. Meanwhile, hepatic antioxidant
      enzyme activities, except for superoxide dismutase activity (p < 0.01),
      glutathione content, and thiobarbituric acid reactive substances levels were not
      significantly different between the groups. Therefore, the current data suggests
      that oxalomalate produces a triglyceride-lowering activity and play a possible
      inhibitory role in fat accumulation. Furthermore, it was not found to affect the
      most antioxidative enzyme activities, glutathione content, and thiobarbituric
      acid reactive substances levels in rats fed normal diet.

PMID- 14595854
TI  - Exact mass measurement on an electrospray ionization time-of-flight mass
      spectrometer: error distribution and selective averaging.
AB  - An automated, accurate and reliable way of acquiring and processing flow
      injection data for exact mass measurement using a bench-top electrospray
      ionization time-of-flight (ESI-TOF) mass spectrometer is described. Using Visual
      Basic programs, individual scans were selected objectively with restrictions on
      ion counts per second for both the compound of interest and the mass reference
      peaks. The selected "good scans" were then subjected to two different data
      processing schemes ("combine-then-center" and "center-then-average"), and the
      results were compared at various ion count limit settings. It was found that, in
      general, the average of mass values from individual scans is more accurate than
      the centroid mass value of the combined (same) scans. In order to acquire a large
      number of good scans in one injection (to increase the sampling size for
      statistically valid averaging), an on-line dilution chamber was added to slow
      down the typically rapid mass chromatographic peak decay in flow-injection
      analysis. This simple addition worked well in automation without the need for
      manual sample dilution. In addition, by dissolving the reference compound
      directly into the mobile phase, manual syringe filling can be eliminated. Twenty
      seven samples were analyzed with the new acquisition and process routines in
      positive electrospray ionization mode. For the best method found, the percentage
      of samples with RMS error less than 5 ppm was 100% with repetitive injection data
      (6 injections per sample), and 95% with single injection data. Afterwards, 31
      other test samples were run (with MW ranging from 310 to 3493 Da, 21 samples in
      ESI+ and 10 in ESI- mode) and processed with similar parameters and 100% of them
      were mass-calculated to RMS error less than 5 ppm also.

PMID- 14595855
TI  - Utilisation of electrospray time-of-flight mass spectrometry for solving complex
      fragmentation patterns: application to benzoxazinone derivatives.
AB  - In this paper we describe the application of electrospray time-of-flight mass
      spectrometry (ESI-TOFMS) to structural elucidation of the fragment ions formed
      from a range of natural and synthetic allelochemical derivatives. The extensive
      mass spectrometric characterisation of ten non-glucosylated benzoxazinone
      derivatives using this method is described here for the first time. The analytes
      include six naturally occurring 1,4-benzoxazin-3(4H)-one derivatives, including
      the hydroxamic acids DIMBOA [2,4-dihydroxy-7-methoxy-2H-1,4-benzoxazin-3(4H)-one]
      and DIBOA [2,4-dihydroxy-2H-1,4-benzoxazin-3(4H)-one], lactams HBOA [2-hydroxy-2H
      1,4-benzoxazin-3(4H)-one] and HMBOA [2-hydroxy-7-methoxy-2H-1,4-benzoxazin-3(4H)
      one], benzoxazolinones BOA [benzoxazolin-2(3H)-one] and MBOA [6-methoxy
      benzoxazolin-2(3H)-one] and four synthetic variations, 2'H-DIBOA [4-hydroxy-2H
      1,4-benzoxazin-3(4H)-one], 2'OMe-DIBOA [2-methoxy-4-hydroxy-2H-1,4-benzoxazin
      3(4H)-one], 2'H-HBOA [2H-1,4-benzoxazin-3(4H)-one] and 2'OMe-HBOA [2-methoxy-2H
      1,4-benzoxazin-3(4H)-one]. Assignments of the mass spectral fragments were aided
      by elemental composition calculation results, comparison of structural analogues
      and background literature, and acquired knowledge regarding feasible structures
      for the compounds. The influence of substituents on the chemical reactivity of
      the compounds with respect to the observed MS behaviour over varying nozzle
      potentials is addressed and, through comparison of the structural analogues,
      generic fragmentation patterns have also been identified.

PMID- 14595856
TI  - Ion trap tandem mass spectrometric determination of F2-isoprostanes.
AB  - A new tandem mass spectrometry (MS/MS) method based on the use of an ion trap
      mass spectrometer for the identification and quantitation of F(2)-isoprostanes
      has been developed. It consists of two solid-phase extractions and two derivation
      steps followed by gas chromatography/negative ion chemical ionization tandem mass
      spectrometry (GC/NICI-MS/MS) analysis. This method is highly selective and
      sensitive and it has been successfully applied to biological samples.

PMID- 14595857
TI  - Gas-phase polar [4+ + 2] cycloaddition with ethyl vinyl ether: a structurally
      diagnostic ion-molecule reaction for 2-azabutadienyl cations.
AB  - The intrinsic reactivity of eight gaseous, mass-selected 2-azabutadienyl cations
      toward polar [4(+) + 2] cycloaddition with ethyl vinyl ether has been
      investigated by pentaquadrupole mass spectrometric experiments. Cycloaddition
      occurs readily for all the ions and, with the only exception of those from the N
      acyl 2-azabutadienyl cations (N-acyliminium ions), the cycloadducts are found to
      dissociate readily upon collision activation (CID) both by retro-Diels-Alder
      reaction and by a characteristic loss of an ethanol (46u) neutral molecule.
      Ethanol loss from the intact polar [4(+) + 2] cycloadduct functions therefore as
      a structurally diagnostic test: 72 u neutral gain followed by 46 u neutral loss,
      i.e., as a combined ion-molecule reaction plus CID 'signature' for N-H, N-alkyl
      and N-aryl 2-azabutadienyl cations. The two N-acyliminium ions tested are
      exceptional as they form intact cycloadducts with ethyl vinyl ether which
      dissociate exclusively by the retro-Diels-Alder pathway.

PMID- 14595858
TI  - Direct analysis of drug candidates in tissue by matrix-assisted laser
      desorption/ionization mass spectrometry.
AB  - Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) has been
      used to directly analyze and image pharmaceutical compounds in intact tissue. The
      anti-tumor drug SCH 226374 was unambiguously determined in mouse tumor tissue
      using MALDI-QqTOFMS (QSTAR) by monitoring the dissociation of the protonated drug
      at m/z 695.4 to its predominant fragment at m/z 228.1. A second drug, compound A,
      was detected in slices of rat brain tissue following oral administration with
      doses ranging from 1-25 mg/kg. Quantitation of compound A from whole brain
      homogenates using routine high-performance liquid chromatography/tandem mass
      spectrometry (HPLC/MS/MS) procedures revealed that concentrations of the drug in
      whole brain varied from a low of 24 ng/g to a high of 1790 ng/g. The drug
      candidate was successfully detected by MALDI-QqTOF in samples from each dose,
      covering a range of approximately two orders of magnitude. In addition, good
      correlation was observed between the MALDI-QqTOFMS intensities at each dose with
      the HPLC/MS/MS results. Thus the MALDI-MS response is proportional to the amount
      of drug in tissue. Custom software was developed to facilitate the imaging of
      small molecules in tissue using the MALDI-QqTOF mass spectrometer. Images
      revealing the spatial localization of SCH 226374 in tumor tissue and compound A
      in brain tissue were acquired.

PMID- 14595859
TI  - Peptide cation-radicals. A computational study of the competition between peptide
      N-Calpha bond cleavage and loss of the side chain in the [GlyPhe-NH2 + 2H]+.
      cation-radical.
AB  - Cation-radicals and dications corresponding to hydrogen atom adducts to N
      terminus-protonated N(alpha)-glycylphenylalanine amide (Gly-Phe-NH(2)) are
      studied by combined density functional theory and Moller-Plesset perturbational
      computations (B3-MP2) as models for electron-capture dissociation of peptide
      bonds and elimination of side-chain groups in gas-phase peptide ions. Several
      structures are identified as local energy minima including isomeric aminoketyl
      cation-radicals, and hydrogen-bonded ion-radicals, and ylid-cation-radical
      complexes. The hydrogen-bonded complexes are substantially more stable than the
      classical aminoketyl structures. Dissociations of the peptide N-C(alpha) bonds in
      aminoketyl cation-radicals are 18-47 kJ mol(-1) exothermic and require low
      activation energies to produce ion-radical complexes as stable intermediates.
      Loss of the side-chain benzyl group is calculated to be 44 kJ mol(-1) endothermic
      and requires 68 kJ mol(-1) activation energy. Rice-Ramsperger-Kassel-Marcus
      (RRKM) and transition-state theory (TST) calculations of unimolecular rate
      constants predict fast preferential N-C(alpha) bond cleavage resulting in
      isomerization to ion-molecule complexes, while dissociation of the
      C(alpha)bond;CH(2)C(6)H(5) bond is much slower. Because of the very low
      activation energies, the peptide bond dissociations are predicted to be fast in
      peptide cation-radicals that have thermal (298 K) energies and thus behave
      ergodically.

PMID- 14595860
TI  - Fragmentation of tunichrome Sp-1 is dominated by an unusual gas-phase
      intramolecular rearrangement.
AB  - Tunichrome Sp-1 is a modified pentapeptide from the ascidian Styela plicata,
      having the structure H-DOPA-DOPA-Gly-Pro-dcDeltaDOPA (where DOPA = 3,4
      dihydroxyphenylalanine and dcDeltaDOPA = decarboxy-(E)-alpha,beta-dehydro-DOPA).
      The tandem mass spectrum of the peptide is dominated by a number of abundant
      fragment ions that involve a gas-phase rearrangement where the dcDeltaDOPA group
      becomes covalently attached to the N-terminus. The high degree of rearrangement
      in Sp-1 compared with a related octapeptide, plicatamide, allowed for detailed
      multiple mass spectrometric (MS(n)) (up to n = 6) experiments, and hence
      permitted a detailed assessment of the origin and routes to the formation of the
      various rearrangement ions. Analyses on both a triple-quadrupole and a quadrupole
      time-of-flight mass spectrometer were made to ascertain whether the gas-phase
      rearrangements observed for tunichrome Sp-1 were unique to an ion trap mass
      spectrometer (i.e. the hypothesis being that perhaps the extended trapping times
      were required to facilitate this unusual gas-phase rearrangement). Interestingly,
      analyses on both the triple-quadrupole and quadruple time-of-flight mass
      spectrometers revealed an identical phenomenon, with the rearrangement fragment
      ions present at approximately the same abundance as the non-rearranged a-, b- and
      y-type sequence ions. We suggest that the smaller size of tunichrome Sp-1
      compared with plicatamide facilitates the transfer of the dcDeltaDOPA group in
      this gas-phase rearrangement. This rearrangement was not observed for peptide
      analogs of tunichrome Sp-1 that did not contain the dcDeltaDOPA at the C
      terminus, confirming that the presence of dcDeltaDOPA is critical for the
      rearrangement.

PMID- 14595861
TI  - A software filter to remove interference ions from drug metabolites in accurate
      mass liquid chromatography/mass spectrometric analyses.

PMID- 14595862
TI  - On the formation of negative ions in atmospheric pressure photoionization
      conditions.

PMID- 14595863
TI  - Current literature in mass spectrometry.

PMID- 14595864
TI  - Assessing the net effect of young maternal age on birthweight.
AB  - Pregnancy during adolescence presents an increased risk for low birthweight,
      which is attributed not only to physiologic immaturity but also to socioeconomic
      and behavioral risk factors associated with adolescence. The independent effect
      of maternal age on birthweight is difficult to ascertain because age is closely
      entangled with these risks. We first examined the effect of being an adolescent
      mother on these risk pathways and then estimated the net effect of maternal age
      on birthweight (weight in grams or low birthweight (<2500 g)) after controlling
      for these risks. We used data on 214 adolescent and 415 adult primiparae and
      their infants from the Cebu Longitudinal Health and Nutrition Survey, a community
      based survey in Metro Cebu, Philippines. Consistent with findings from other
      studies, adolescents in this sample were more socioeconomically disadvantaged,
      had poorer nutritional status during pregnancy, and received less prenatal care
      than adults. Bivariate analyses showed that infants of adolescents had a lower
      mean birthweight and were more at risk of low birthweight compared to those born
      to older mothers. When socioeconomic, biological, and behavioral risk factors
      were controlled for, young maternal age ceased to have an effect on birthweight
      in grams but remained a significant predictor of low birthweight. The common
      pathways through which maternal age influenced both birthweight variables were
      through its effects on maternal height and weight-for-height during pregnancy. In
      the model predicting birthweight in grams the maternal age effect was further
      manifested through prenatal care utilization.

PMID- 14595865
TI  - Growth status and obesity of Hopi children.
AB  - The purpose of this study was to examine the growth status and prevalence of
      underweight, overweight, and obesity in Hopi children. Subjects were 263 (117
      males, 146 females) Hopi children 6-12 years of age. Stature and mass were
      measured and the body mass index (BMI) was calculated. Body size variables were
      plotted relative to age- and sex-specific reference data and the prevalence rates
      for underweight, overweight, and obesity were estimated using the BMI as the
      criterion. Age-specific sex differences were compared using independent samples t
      tests. In both sexes, mean age-specific stature appeared to be relatively stable
      around the 50th percentile of reference values. Mean age-specific mass appeared
      to be relatively stable between the 50th and 90th percentiles of the reference
      values, while the mean BMI tended to fluctuate about the 85th percentile.
      Approximately 23% of Hopi children were classified as overweight and an
      additional 24% were classified as obese. Only two subjects were categorized as
      underweight. The results are consistent with other reports that childhood obesity
      is a serious public health concern among Native Americans. Further study is
      warranted to examine the causes of the high prevalence rates of pediatric obesity
      among Native Americans and the effectiveness of prevention and intervention
      programs.

PMID- 14595866
TI  - Body size and shape and glycemic control among Maya women in rural Yucatan.
AB  - Studies on relationships between aspects of physique and glucose physiology
      generally focus on clinical glucose tolerance or on fasting glucose or insulin
      assays showing glycemic status at the time of testing. Little work has examined
      the associations between body variables and glycemic control, or average past
      glucose levels in regular living conditions. The aim of this research was to
      investigate connections between body size and shape and glycemic control. The
      sample consists of 60 nondiabetic Maya women, ages 40-85 years, residing in 16
      rural villages around Merida, Yucatan. Body morphology was assessed through
      anthropometric and derived measures of size and shape, including indicators of
      fat distribution and general adiposity. Glycemic control was measured through
      microvenous samples analyzed for glycated blood proteins HbA(1c) and fructosamine
      to demonstrate average circulating glucose under customary living conditions
      during the previous several months and weeks. Four-variable regression models
      explain 17% of the variance in HbA(1c) and 25% of the variance in fructosamine.
      Arm circumference has the largest positive effect on HbA(1c), while weight has
      the greatest positive impact on fructosamine. The predictor with the largest
      negative effect on both glycated blood proteins is calf circumference. In
      general, variables reflecting overall adiposity and central adiposity demonstrate
      positive associations with HbA(1c) and fructosamine, whereas lean body measures
      exhibit negative associations. Findings support the value of glycated blood
      proteins and of less common anthropometric measures, such as calf circumference,
      in population research on morphological relations with glycemia.

PMID- 14595867
TI  - Prevalence of overweight among adolescent females in the United Arab Emirates.
AB  - The purpose of the study was to investigate the prevalence of overweight in
      adolescent females in the United Arab Emirates (UAE). A total of 898 females,
      ages 11-18 years, were recruited from five of the seven Emirates with the highest
      resident Emirati population. Height, weight, triceps skinfold thickness (TSF),
      and mid-upper-arm circumference were measured in each subject. Reference data
      from the National Health and Nutrition Examination Surveys (NHANES) were used for
      comparison. At risk for overweight or overweight were defined as a body mass
      index (BMI, kg/m(2)) >or=85-95th percentile and >or=95th percentile,
      respectively. Mean values for BMI and TSF at all ages were higher than the 50th
      percentile (median) of the NHANES reference data. Using the BMI classification,
      14% and 9% of all subjects were classified as at risk for overweight or
      overweight, respectively. The proportion of subjects at risk for overweight
      ranged between 7-19% and the prevalence of overweight ranged between 6-15%. The
      proportion of subjects with a BMI >or=85 percentile ranged from 15% at age 17
      years to 33% at age 11 years. Furthermore, 27% and 28% of subjects ages 11 and 12
      years, respectively, were above the TSF 90th percentile. These two age groups
      also showed a high prevalence of overweight using the BMI classification. In
      conclusion, the findings from our study suggest that a high proportion of
      adolescent females in the UAE are overweight or at risk for overweight. The
      consequences of this are a serious concern for public health and need to be
      addressed.

PMID- 14595868
TI  - Patterns for the initiation of breastfeeding in humans.
AB  - Establishment of lactation has important biological and emotional health
      consequences for the newborn. Even so, substantial variation within a culture and
      among different cultures is seen in the onset of breastfeeding. Parametric
      mixture models are used to explore this variation and to uncover general human
      patterns for the initiation of breastfeeding. The model components reflect two
      hypothesized patterns of behavior. The first component is a "natural" pattern of
      breastfeeding that reflects, to some extent, a general mammalian behavior. The
      second component arises through culturally mediated behaviors that affect the
      initiation of breastfeeding. The model was fit by maximum likelihood to interval-
      and right-censored observations on 26220 mother-infant pairs collected from 25
      previously published studies of breastfeeding behavior. Both model components
      were clearly statistically identified. Effects of cultural and geographic
      covariates were found to have significant effects on all components of the model.
      Although there is clear evidence for two distinct patterns of behavior in the
      initiation of breastfeeding, the results suggest that learned behaviors play an
      important role in mediating even "natural" breastfeeding behavior.

PMID- 14595869
TI  - Enzyme polymorphisms, smoking, and human reproduction. A study of human placental
      alkaline phosphatase.
AB  - We investigated the possible effects of placental alkaline phosphatase (PLAP)
      genotype on the deleterious action of maternal smoke on intrauterine survival and
      birthweight. PLAP is a highly polymorphic enzyme with several alleles associated
      with different enzymatic activities. PLAP is produced by the embryo and is found
      in maternal blood, where it is responsible for the rise of serum alkaline
      phosphatase during pregnancy. Two hundred and fourteen Caucasian consecutive
      newborn infants delivered in the Maternity Department of the University of Rome
      La Sapienza Hospital were studied. Infants from smoking women 28 years or older
      show a strong decrease of both PLAP*1/*1 and *2/*2 homozygous types and a marked
      deviation from Hardy-Weinberg expectation, thus suggesting a different lethal
      effect of smoke depending on PLAP genotype and maternal age. In infants from
      smoking mothers there is a decrease of birthweight that is much less evident and
      statistically not significant in infants carrying the PLAP*1/*1 genotype as
      compared to other genotypes. The difference between PLAP genotypes concerning
      birthweight is more marked in women older than 28 years than in younger ones.
      This suggests that the effects of smoke on birthweight are also dependent on PLAP
      and maternal age.

PMID- 14595870
TI  - Secular trends in variables associated with the metabolic syndrome of North
      American children and adolescents: a review and synthesis.
AB  - The aim of this article is to summarize and critique reports from selected large
      scale population health surveys (U.S. and Canada national health surveys (e.g.,
      National Health and Nutrition Examination Survey, Youth Risk Behavior Survey, and
      Canada Fitness Survey), and active research programs in preventive pediatric
      cardiology (i.e., Bogalusa Heart Study, Princeton Lipids Study, and Minneapolis
      Blood Pressure Study)) pertaining to the secular trend in variables associated
      with the metabolic syndrome of North American youth. These surveys were chosen
      since they have published peer-reviewed articles on the topic and consist of
      relatively large samples. The increased body mass index and prevalence of
      overweight and obesity are clear, particularly over the past two decades. The
      secular increase in overweight and obesity cannot be linked to available self
      report data on physical activity or diet, although measurement issues need to be
      considered. The emergence of Type II diabetes in adolescents parallels the
      increase in obesity; however, subsequent changes in blood lipids and blood
      pressure are less clear. There is some evidence to suggest adverse changes in the
      blood lipid profile. Aerobic fitness, as determined by maximal oxygen consumption
      (VO(2max)), has not appeared to change in youth except perhaps for adolescent
      females. The results suggesting the emergence of metabolic syndrome X during
      childhood and adolescence are discussed in the context of perturbation and
      dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. It can be
      suggested that a subsistent lifestyle consisting of increased lifestyle activity
      (not exercise per se), a prudent diet, adequate sleep and rest, and stress
      reduction be advocated to combat diseases of Western Civilization/metabolic
      syndrome that have affected North American children (and adults) in recent years.
      The results also highlight the importance of population surveillance of obesity,
      physical activity, and dietary intake and cardiovascular health of children into
      the 21st century.

PMID- 14595871
TI  - Decline in enamel hypoplasia in relation to fluoridation in Australians.
AB  - Enamel hypoplasias are thought to represent calcification disruption indicative
      of metabolic stress during development. Hypoplasias of permanent maxillary
      central incisors and mandibular canines have undergone a notable reduction in
      frequency between Euro-Australian twins born around 1965 and those born ca. 1990.
      Even when scored very liberally these linear defects are 3.1-4.6 times as
      prevalent in the earlier Australians, and the discrepancy is proportionately
      greater among strictly scored defects. Likely correlates of this secular trend
      logically include reduced childhood fevers and clinical intervention to reduce
      circum-natal stresses acting on cotwins. However, fluoridation of metropolitan
      water has emerged as the statistically strongest hypoplasia-preventing factor.

PMID- 14595872
TI  - Urban-rural contrasts in the physical fitness of school children in Oaxaca,
      Mexico.
AB  - The physical fitness of school children resident in an urban colonia and in a
      rural indigenous community in Oaxaca, southern Mexico, was compared. Two measures
      of performance-related fitness (standing long jump, 35-yard dash [32 m]) and four
      measures of health-related fitness (grip strength, sit and reach, timed sit-ups,
      distance run) were taken on 355 rural (175 boys, 184 girls) and 324 urban (163
      boys, 161 girls) school children, 6-13 years of age. Urban children were
      significantly taller and heavier than rural children. Absolute grip strength did
      not consistently differ between rural and urban children, but when adjusted for
      age and body size, strength was greater in rural children. Explosive power
      (standing long jump) and abdominal strength and endurance (timed sit-ups) were
      better in urban than in rural children without and with adjustment for age and
      body size. Urban-rural differences in running speed (dash) and flexibility (sit
      and reach) varied by age group and sex. Younger rural children and older urban
      girls performed better in the distance run, whereas older rural and urban boys
      did not differ in endurance. The size advantage of urban children does not
      necessarily translate into better levels of performance- and health-related
      physical fitness. The observed differences may be related to activity habits
      associated with school physical education and lifestyle in the respective
      communities.

PMID- 14595873
TI  - Locus-specific genetic diversity between human populations: an analysis of the
      literature.
AB  - The debate over classification of the human species according to racial or
      continental lines has involved reports on genetic differences in allele
      frequencies of a number of loci with important biomedical functions. Such
      differences are in contrast with the fact that, for human beings, intrapopulation
      genetic diversity is larger than that seen between populations. In an attempt to
      address the hypothesis that certain genes show high interpopulation diversity due
      to selective pressure, the literature was surveyed to quantify such diversity
      using Wrights Fst statistic. The gene-specific Fst values were then compared to
      pairwise population values of Fst taken over a large number of genes, which
      presumably reflect mostly neutral mechanisms of genetic diversity such as drift.
      The results showed that the majority of pairwise population values of Fst for
      over 30 genes of biomedical significance were either below or within the expected
      limits of Fst based on published values. These results do not support the idea
      that positive or diversifying natural selection plays an important role in
      increasing genetic diversity, even in genes that might be expected to be subject
      to selection pressure. Balancing selection, whereby the degree of genetic
      diversity is actually lower than that expected, appears to occur more frequently
      for these genes. The fact that allele frequency differences between populations
      might be "statistically significant" does not therefore necessarily imply a
      degree of genetic diversity greater than would be expected due to nonselective
      mechanisms.

PMID- 14595874
TI  - Historical genetics: spatiotemporal analysis of the formation of the Brazilian
      population.
AB  - A total of 1037 individuals living in five different sociogeographic regions of
      Brazil were studied in relation to 12 short tandem repeat polymorphisms. The
      objective was to assess the degree of European, African, and Amerindian
      contributions to their gene pools. Although most of the genetic variability was
      found within regions, significant differences were also observed between regions.
      The estimated relative proportions of the above-indicated continental
      contributions showed intermediate values between those obtained with uniparental
      (mtDNA, Y-chromosome) data, and a higher percentage of European heritage as
      compared to previous autosome results. A north-south trend of increasing European
      contribution was also found, in agreement with the history of the Brazilian
      population.

PMID- 14595877
TI  - [Misuse of the technique].

PMID- 14595878
TI  - [Urological terminology in Francisco Diaz: an example in the history of the
      Spanish language].
AB  - OBJECTIVES: The work "Tratado nuevamente impreso de todas las enfermedades de los
      rinones, vejiga y carnosidades de la verga y orina" from Francisco Diaz is the
      first Urology treaty and the main urologic text from the spanish renaissance. The
      idea that prompted our work was to collect the Romance language from a text about
      urology dated at the end of the XVI century. Its interest consists, on the one
      hand in the lack of similar studies, and on the other in the novelty resulting
      from the fact that the author decided to write in Romance language at a moment in
      which scientific treaties were written in Latin. METHODS: We performed a
      meticulous reading of the treaty on a facsimile edition of the original of the
      same title edited in Madrid in 1588. We extract 1.288 medical terms that we
      consulted in three modern dictionaries to analyze the lexicon used by Diaz in its
      composition. We analyze the words from the point of view of their make up and
      ethimology; we review the meaning of the medical terms in relation to their
      current use--meaning conservation or loss--, and also the date of appearance of
      those terms in the spanish language, to know how many of them appeared in the
      work of Diaz for the first time, and to know the conservation or loss of the
      meaning that Diaz gave them currently. RESULTS: We extract 1.288 medical terms,
      195 of them have been conserved with the same meaning from their origin to date;
      on the contrary, 35.5% are not found in either of the three dictionaries, so that
      they are medical terms used by Francisco Diaz for the first time and that were
      erased by time. 543 medical terms were contributions from Diaz in their first
      written appearance. CONCLUSIONS: The author performs a magnificent study in which
      he analyzes and explains his experience, his knowledge, and his deductions on
      everything referred to urinary tract diseases, with great expertise, offering at
      the same time an extraordinary living document of his time. It is also an
      extensive source of medical and general knowledge, provided from the great
      culture, maturity, and classic education of the author. It is a pleasant-to-read
      and easy-to-understand work thanks to its exquisite composition and perfect use
      of the the Romance language, well defined syntax, rich vocabulary, and abundance
      of practical examples.

PMID- 14595879
TI  - [Current status of the diagnosis and treatment of urinary incontinence in Spain].
AB  - OBJECTIVES: To perform a review of the available literature about urinary
      incontinence (UI) epidemiology, diagnosis, treatment and results, mainly focusing
      on the stress UI, to expose the features about which may there be a consensus,
      and those that will need future research work. METHODS: Systematic review of the
      available spanish bibliography about the proposed topic. RESULTS: They prevalence
      of female UI in Spain varies between 20 and 50%, depending on age. There are no
      available data about incidence. The onset age of this disease has not been
      directly studied in any of the works reviewed, although from them it can be
      deduced that it is around 55 years. The patient with UI tends to hide the
      problem, and generally, doctors tend to not recognize it as a treatable
      pathology, so that supposedly there is a high prevalence off occult UI. UI is
      frequently related to many other pathologies. The diagnosis of UI in Spain is
      generally made following the international criteria collected in the available
      clinical practice guidelines, which describe the diagnostic process to be
      followed in detail. Diagnostic tests generally used in the diagnosis of UI have a
      sensitivity higher than 70% and a specificity around 65%. First choice treatment
      is conservative, including the use of physiotherapy by means of pelvic muscle
      exercises. It is considered that pharmacological treatment has not much effect,
      although it doesn't seem to have been investigated in depth in Spain. Surgery, in
      any of its various techniques, is the second choice treatment. Although studies
      on health results for UI are scarce, it is known that about one-quarter of all
      patients declare that their quality of life is affected. Economic studies about
      UI are very rare also and only offer results about some treatment items.
      CONCLUSIONS: To better precise the incidence and prevalence of UI in Spain, the
      performance of population epidemiological studies seems necessary. The weakness
      of the diagnostic process of UI in Spain appears to be detection in the initial
      stages. It is also necessary to have studies evaluating conservative and
      pharmacological therapies currently performed; these studies would allow to
      establish comparisons with the surgical treatments usually performed. It is also
      necessary to have studies that include cost calculation for integrated costs for
      UI.

PMID- 14595880
TI  - [Primary psoas abscess: report of 5 new cases. Review of the literature].
AB  - OBJECTIVES: We report 5 new cases of primary psoas abscess in this review. We
      describe the various pathogen agents involved in the development of this disease,
      as well as the etiopathogenesis, which is explained by several theories, being
      the most commonly accepted hematogenous dissemination from a septic focus. In the
      same way, we refer the most interesting clinical data and the value of current
      diagnostic tests, among which are abdominal x-ray (KUB), ultrasound, isotope
      scan, and CT scan, being this latter the ideal diagnostic test for these
      processes. METHODS: Retrospective study from 1985 to 2000, including a total of 5
      patients with an average age of 48.2 years. RESULTS: 4 of these 5 patients were
      males, and two of them had documented history of addiction to parenteral drugs
      and chronic alcoholism respectively. All patients presented with lumbar pain,
      four of them with fever, 2 functional impotence and 1 mass effect. Four of them
      had increased white blood cells count; ultrasound was diagnostic in one case
      only, and CT scan in all 5. Blood cultures were positive in three cases, being
      Staphylococcus Aureus the germ isolated from the pus in four cases. The four
      patients treated had a positive outcome without recurrence to date. CONCLUSIONS:
      The reappearance of primary abscesses in young population with history of
      alcoholism or addiction to parenteral drugs. CT scan is the diagnostic tests of
      choice. Percutaneous drainage has good results and is less aggressive therapeutic
      option for this disease.

PMID- 14595881
TI  - [Assessment of the Gleason score in biopsies and specimens of radical
      prostatectomy].
AB  - OBJECTIVES: To evaluate the similarity between Gleason grade on prostate biopsies
      and their final result after radical prostatectomy. METHODS: We retrospectively
      review the medical records of 129 patients who underwent radical prostatectomy.
      Mean PSA value was 10.7 ng/ml. The relationships between pathological reports of
      biopsies and radical prostatectomy specimens, and other variables such as PSA
      were established. RESULTS: Globally, 72 cases (55.8%) were in the same risk group
      by grade on biopsy and surgical specimen. Biopsy result was understaged in 48
      cases (37.2%) and overstaged in 9 cases (7%). We found biopsy understaging in 42
      cases (60%) in the low grade group, 6 cases (10.9%) in the intermediate grade
      group, and 50% in the high grade group, although in this latter the number of
      cases was very low. CONCLUSIONS: Overall biopsy understaging was 37.2%, being
      much more evident in low grade tumors (60%). It seems that understaging was
      greater when PSA > 10 ng/ml, although differences were not significant.

PMID- 14595882
TI  - [New urodynamic data of sensory urgency in women].
AB  - OBJECTIVES: Irritative bladder symptoms are common in females. Besides,
      micturition disorders are occasionally associated. Sensory urgency is one of the
      syndromes that include the symptoms. This entity is a urodynamic condition
      defined by the presence of pain or urgency during the filling phase without
      associated involuntary detrusor contractions. Although it is well defined
      urodynamically, the corresponding nosological entity is unknown. The objective of
      this study is to check if it has any relationship with the capability of the
      abdominal press to participate during micturition. METHODS: We perform a
      transversal study comparing a group of 25 females (mean age 50.2 yr.) with the
      diagnosis of sensory urgency and a group of 48 patients paired by age. Urodynamic
      data from both groups were reviewed, and the existence of significant differences
      was determined for flowmetry, bladder capacity (cystometry), and participation of
      the abdominal press during voiding (voiding flow-detrusor pressure test).
      RESULTS: Patients with sensory urgency showed significantly lower maximum and
      mean flow rates than controls. Bladder capacity was similar in both groups, but
      bladder capacity at first desire to void was significantly lower in the sensory
      urgency group. No significant differences were observed between the groups on
      participation of the abdominal press. However, if the comparison was performed
      between the subgroup of patients with sensory urgency who also referred
      suprapubic pain during filling and controls, then there was a significantly
      higher participation of the abdominal press during voiding in this group.
      CONCLUSIONS: Data from this study are compatible with the hypothesis that sensory
      urgency is associated with bladder contractile capacity alterations. This
      association would be more evident in the group of patients in which sensory
      urgency is accompanied by hypogastric pain during filling, which could constitute
      a subgroup with higher progression risk.

PMID- 14595883
TI  - [Treatment of urinary calculi in transplanted kidney with extracorporeal shock
      wave lithotripsy].
AB  - OBJECTIVES: To know the factors associated to a successful result in the
      treatment of kidney transplant lithiasis by extracorporeal shockwave lithotripsy
      (ESWL). METHODS: From 850 kidney transplants performed at our center, we analyze
      15 patients who developed urinary stones. Successful result by ESWL was the
      dependent variable, and size, location, and multiplicity of the stones were
      independent variables. Associations between variables were studied by the chi
      square test (categorical variables) and the U-Mann Whitney test (continuous
      variables). RESULTS: Incidence was 1.76%. ESWL effectiveness was 87%; it was
      greater in solitary stones than in multiple stones (p = 0.001). No significant
      differences were found for stone size, although largest stones had a high risk
      for insertion of a nephrostomy tube (p = 0.013). Finally, ESWL was more effective
      for stones located at the ureteral anastomosis, although this difference was
      found not significant. CONCLUSIONS: The treatment of kidney transplant lithiasis
      by ESWL has an effectiveness of 87%. The best result was found for solitary
      stones located at the ureteral anastomosis.

PMID- 14595884
TI  - [Effectiveness and safety of the treatment with sildenafil (Viagra) in patients
      with erectile dysfunction and arterial hypertension].
AB  - OBJECTIVES: To evaluate the efficacy and safety of sildenafil in the treatment of
      erectile dysfunction in hypertensive patients taking antihypertensive drugs, and
      to investigate factors associated to treatment failure. METHODS: Observational
      prospective study comparing two groups of patients suffering from erectile
      dysfunction with or without hypertension. Patients were evaluated by anamnesis,
      physical examination, blood tests, and the International Index of Erectile
      Function (IIEF). Blood pressure was measured before and after treatment with an
      automatic digital oscillometric device. RESULTS: Erections improved in 88.2% and
      91.7% of the patients with an without hypertension respectively. On the initial
      visit 55.2% of all patients had severe dysfunction, which was reduced after
      sildenafil treatment to 4.7%. Diastolic arterial blood pressure, evaluated in
      random measures, was slightly reduced after starting treatment with Viagra. No
      significant adverse events were registered. CONCLUSIONS: Oral treatment with
      sildenafil in patients with erectile dysfunction and hypertension is effective,
      well-tolerated and does not produce pharmacologic interactions with
      antihypertensive drugs.

PMID- 14595885
TI  - [Propoleum and Peyronie's disease].
AB  - OBJECTIVES: Peyronie's disease is a plastic penile induration which represents a
      well-known problem affecting men in their middle age, who suffer penile
      incurvation during erections, pain and poor consistency at the site of
      incurvation. There is no satisfactory treatment for this disease. A patient with
      Peyronie's disease who received propoleum treatment for a giardiasis infection
      referred spontaneous improvement of this penile incurvation as treatment cycles
      were repeated. So, we decided to treat a group of patients with this pathologic
      entity with propoleum to evaluate its efficacy. METHODS: Initially, 25 patients
      were studied, only 13 completed the study 6 months later. VARIABLES: age, penile
      incurvation, presence or not of pain with erections, detection and measurement
      (cm) of the fibrous plaque on physical examination and ultrasound, and
      description of its radiologic characteristics. Propoleum powder (300 mg) was
      administered for 6 months. RESULTS: Patient age was predominantly between 51 and
      60 years. Upward deviation was the most frequent presentation; it disappeared in
      2 patients in the "Improved" group. Most patients had no pain. 3 patients out of
      13 had no plaque on examination at the end of treatment. Regarding incurvation 10
      patients improved, 2 improved slightly, and only one improved somewhat during the
      first three months but then after remained the same. Penile x-ray was not useful
      as a diagnostic test; penile ultrasound was greatly useful. CONCLUSIONS: Penile
      incurvation improved in 77% of the patients. Fibrous plaques were reduced more
      than 0.5 cm on ultrasound (average 0.64 cm).

PMID- 14595886
TI  - [Study of propoleum dosage in Peyronie's disease].
AB  - OBJECTIVES: To determine the optimal dose for propoleum caps in Peyronie's
      disease. METHODS: We evaluated two groups of 17 patients each, analyzing pain and
      plaque size on physical and ultrasound examination, before and after treatment.
      Group A patients received caps with 300 mg of propoleum powder daily for six
      months, and Group B 900 mg. RESULTS: Predominant ages were between 41 and 70
      years. More than half the patients in group A had pain; more than half the
      patients in group B did not have pain; considering both groups there were more
      patients without pain. Physical reduction of the plaque: Group A: 0.6 cm, Group
      B: 0.8 cm. Ultrasound reduction of the plaque: Group A: 1.3 cm, Group B: 0.8 cm.
      In the higher dose group (B) clinical and ultrasound improvement started earlier.
      79.4% of the treated patients evaluated preferred improvement or slight
      improvement, being this result statistically significant. CONCLUSIONS: Pain is
      not always an accompanying symptom in Peyronie's disease. Both doses administered
      reduced the size of the plaque, but the higher one has an earlier improvement. We
      may consider propoleum administered in this way another treatment option for this
      disease, with good results and low cost.

PMID- 14595887
TI  - [Single kidney derived to sigmoid for urinary tuberculosis: remarkable morpho
      functional status 51 years after surgery].
AB  - OBJECTIVES: To report a solitary kidney ureterosigmoidostomy (US) secondary to
      urinary tuberculosis which we believe has the longest follow-up in the world
      literature. With this purpose we performed an analysis of the experience with
      such a urinary diversion published in our country, which maybe has been
      exaggeratedly excluded during the last decades. METHODS: Male patient who was
      diagnosed of urinary tuberculosis at the age of 17 in 1950 and underwent left
      nephrectomy. Due to bladder retraction he underwent cystectomy and urinary
      diversion to the sigmoid colon following the technique by Coffeyone year later.
      Follow-up for half a century has demonstrated an excellent outcome with almost no
      effect on renal function and urinary tract morphology, and very low incidence of
      infectious complications. DISCUSSION: We review cases of US with longest follow
      up in the literature, finding a remarkable number of cases followed for more than
      30 years. It is true they were performed almost exclusively for benign diseases.
      There is only one published citation in which US was indicated for bladder
      carcinoma and after 31 years of follow-up patient died from a nonrelated disease
      at the age of 85. We also review the scarce number of papers published in our
      country, focusing on the "Ponencia al Congreso Nacional de Urologia 1983" which
      presented a thorough review of "urinary diversions" with the cooperation of 27
      Spanish centers.

PMID- 14595888
TI  - [Radical prostatectomy in hemophiliac patient].
AB  - OBJECTIVES: To describe a case of organ-confined prostate cancer in a patient
      with hemophilia who was treated with radical prostatectomy. METHODS: We report
      the medical history emphasizing the haematologic, anesthetic and surgical
      management. RESULTS: We demonstrate that a successful retropubic radical
      prostatectomy may be undertaken in a hemophilic patient, without major morbidity,
      after performing an adequate evaluation and taking pertinent measures.
      CONCLUSIONS: Retropubic radical prostatectomy is a therapeutic option which can
      be undertaken in the treatment of hemophilic patients with organ confined
      prostate cancer, successfully and with low morbidity. Therefore, this therapeutic
      option should be considered among those to be offered to these patients.

PMID- 14595889
TI  - [Ovarian vein syndrome. Report of 2 cases].
AB  - OBJECTIVES: To report the clinicae characteristics and treatment of the ovarian
      vein syndrome. METHODS: We studied two cases of female patients with obstructive
      uropathy secondary to ovarian vein syndrome cared for at our department over the
      last 4 years. RESULTS: Both cases were treated surgically. Postoperative outcomes
      were satisfactory. CONCLUSIONS: The ovarian vein syndrome is rare. Surgery is the
      treatment of choice for symptomatic cases.

PMID- 14595890
TI  - [Foamy carcinoma of the prostate].
AB  - OBJECTIVES: We report the first case of prostatic foamy gland carcinoma in the
      Spanish literature. METHODS: Case of a 69-year-old male who consulted for PSA
      elevation up to 101 ng/ml. Transrectal ultrasound showed a heterogeneous gland
      with a hipoechogenic area in the right lobe and possible capsular disruption. Six
      ultrasound guided needle biopsies were performed. The samples from the right lobe
      were reported as Gleason 6 foamy cell prostatic adenocarcinoma. RESULTS:
      Prostatic foamy cell carcinoma is a rare tumor, and so are its bibliographic
      references. Its cells lack of prominent nucleus and nucleoli. They show a
      plentiful and xanthomatous cytoplasm, with abundant intracytoplasmic pink
      secretions characteristically. It may be mistaken with low grade adenocarcinomas,
      and it is essential to differentiate it from the clear cell prostatic
      adenocarcinoma, prostatic adenosis, and even from benign prostatic hyperplasia.
      It usually has an intermediate grade, with a Gleason score greater than 4.

PMID- 14595891
TI  - [Bilateral renal solitary fibrous tumor].
AB  - OBJECTIVES: We report the first case of bilateral renal solitary fibrous tumor
      diagnosed in a patient suffering from tuberous sclerosis. METHODS: From the
      bibliographic review, only 15 cases of solitary fibrous tumor have been described
      in the kidney. We did not find any case of simultaneous bilateral involvement. We
      did not find any case described in a patient with tuberous sclerosis either, as
      the present case, being a 51-year-old female with presenting with a big abdominal
      mass arising from the left kidney (25 cm) and another 2 cm mass in the right
      kidney. CONCLUSIONS: We emphasize the extreme rarity of this tumor in the kidney.
      It has benign characteristics and behavior, and good prognosis, but requires
      surgical treatment to obtain a proper histopathologic diagnosis, based on immuno
      histochemical studies.

PMID- 14595892
TI  - [Prostatic abscess: report of a case].
AB  - OBJECTIVES: To report one case of prostatic abscess which required emergency
      surgical treatment because of its aggressive evolution. METHODS: We describe the
      case of a 61-year-old male patient who was diagnosed of prostatic abscess in the
      emergency room, and initially underwent conservative treatment with antibiotics
      and urinary diversion. Due to clinical impairment to septicemia and upper urinary
      tract involvement we decided to perform a surgical perineal drainage. RESULTS:
      The septic clinical picture resolved immediately, but he presented a prostatic
      perineal fistula in the intermediate postoperative period which resolved with
      prolonged urinary diversion by cystotomy catheter. HIV serologies were performed
      considering the aggressiveness of picture; they were positive. CONCLUSIONS: We
      emphasize this case because of the great aggressiveness that presented, possibly
      due to factors such as diabetes and immunosuppression (HIV). Provided the great
      variety of presentations of this disease, a high degree of suspicion must be
      exercised for its diagnosis, and once the diagnosis is got immediate treatment is
      recommended. We review etiopathogenic factors, clinical findings, diagnosis and
      therapeutic options.

PMID- 14595893
TI  - [Giant bladder diverticulum presenting as inferior vena cava syndrome].
AB  - OBJECTIVES: To report the case of a giant bladder diverticulum clinically
      presenting with symptoms of inferior vena cava compression. METHODS: Patient
      under study because of inferior limbs edema who underwent ultrasound that found a
      giant bladder diverticulum. RESULTS: Diverticulectomy plus adenomectomy were
      performed. CONCLUSIONS: Acquired giant bladder diverticula are very rare; they
      should be treated surgically to avoid possible complications.

PMID- 14595894
TI  - [A case of genital transposition].
AB  - OBJECTIVES: To report the case of a 64-year-old male patient who was diagnosed of
      complete genital transposition. METHODS: Physical examination, blood tests, and
      radiologic tests (ultrasound, intravenous urography) were performed. RESULTS:
      Physical examination findings were limited to the genital area. There was a
      complete genital transposition with normal testicles, epididymis, and spermatic
      cord. Both blood and radiologic tests were normal. Patient did not refer any
      symptoms of dysuria, and he had normal sexual intercourse, so that he refused the
      proposed surgical treatment. CONCLUSIONS: Genital transposition is a rare
      malformation, it is not life-threatening in most cases, but some cases have
      multiple coexistent malformations, some of them incompatible with life, partially
      justifying the scarcity of reports.

PMID- 14595895
TI  - Cervical lymph node enlargement on the right side as the initial manifestation of
      metastatic prostate cancer.
AB  - OBJECTIVES: Cervical lymph node enlargement (LAP) due to metastatic spread is an
      uncommon manifestation of prostatic adenocarcinoma. In case of non-regional
      lymphatic spread, left supraclavicular region was found to be the most common
      site (1,2,3) whereas right sided metastatic lymph node involvement has been
      extremely uncommon. METHODS: We here in describe a case of a 75 year-old man who
      had an enlarged cervical lymph node for a year which subsequently proved to be
      involved by metastatic adenocarcinoma of the prostate. CONCLUSIONS: Although,
      prostate cancer rarely metastasize to the cervical lymph node chain it should
      always be considered in the differential diagnosis of metastatic lymph node
      enlargement in the cervical area of elderly men.

PMID- 14595896
TI  - The GMO war.

PMID- 14595898
TI  - The case for instant evolution.

PMID- 14595897
TI  - [DNA: patenting also the "junk"].

PMID- 14595899
TI  - The ecological risks of transgenic plants.
AB  - Biotechnologies have been utilized "ante litteram" for thousands of years to
      produce food and drink and genetic engineering techniques have been widely
      applied to produce many compounds for human use, from insulin to other medicines.
      The debate on genetically modified (GM) organisms broke out all over the world
      only when GM crops were released into the field. Plant ecologists,
      microbiologists and population geneticists carried out experiments aimed at
      evaluating the environmental impact of GM crops. The most significant findings
      concern: the spread of transgenes through GM pollen diffusion and its
      environmental impact after hybridisation with closely related wild species or
      subspecies; horizontal gene transfer from transgenic plants to soil microbes; the
      impact of insecticide proteins released into the soil by transformed plants on
      non-target microbial soil communities. Recent developments in genetic engineering
      produced a technology, dubbed "Terminator", which protects patented genes
      introduced in transgenic plants by killing the seeds in the second generation.
      This genetic construct, which interferes so heavily with fundamental life
      processes, is considered dangerous and should be ex-ante evaluated taking into
      account the data on "unexpected events", as here discussed, instead of relying on
      the "safe until proven otherwise" claim. Awareness that scientists,
      biotechnologists and genetic engineers cannot answer the fundamental question
      "how likely is that transgenes will be transferred from cultivated plants into
      the natural environment?" should foster long-term studies on the ecological risks
      and benefits of transgenic crops.

PMID- 14595900
TI  - Role of connectivity in immune and neural network models: memory development and
      aging.
AB  - In this paper we analyzed how connectivity (defined as number of connections
      between network elements) can affect the memory capacity of a network-based model
      of the Immune System (IS) and of a model of the Nervous System (NS) synaptic
      plasticity (BCM model). The key point is the concept of competition between the
      characteristic variables that represent the response of such systems to
      environmental stimuli: the clonal concentrations for the IS, and the neuron
      responses for the BCM model. The memory states of both systems are characterized
      by a high selectivity to specific input patterns, reflecting a similar behaviour
      of their development rules. This selectivity property of memory states can be
      controlled by changing the degree of the internal connectivity in each system. We
      can explain the changes occurring in IS memory states during lifespan as due to a
      reshaping of its internal connectivity. This assumption is in agreement with
      experimental observations, reporting an increase of IS memory cells during
      lifespan. The change of connectivity in the BCM model leads to the introduction
      of quasilocal variables governing the plasticity of groups of synaptic junctions.
      This could be interpreted as the result of a refinement of neuron internal
      mechanisms during development, or it could be seen as a different learning rule
      deriving from the original BCM theory. We argue that connectivity seems to play
      an important role in a large class of biological systems controlled by
      competition mechanisms. Moreover, changes in connectivity may lead to changes in
      memory properties during development and aging.

PMID- 14595901
TI  - The contribution of plant biology to the concept of virus (1886-1917).
AB  - Between 1860 and 1880 the so-called "theory of the infective germ", which stated
      in final way that every infectious disease was produced by a living pathogen
      agent, achieved great consent. The criteria of determining the presence of
      infectious pathogens (fungi, bacteria, protozoa) were established by "Koch's
      postulate", a set of experimental procedures conceived for isolating and
      determining single pathogens. In the last quarter of the 19th century became
      however evident that the agents of severe infectious diseases could not be
      identified through the "postulates". These agents could not be seen in light
      microscopy nor cultured in vitro but could pass through the thin pores of filters
      which hold back cellular micro-organisms. This last characteristic became a
      selective method to recognise these peculiar agents, from then named "filterable
      viruses". Most microbiologists considered the filterable viruses as living micro
      organisms because of their extraordinary capacity of in vivo proliferation, and
      the impossibility of pointing out their structures was due to limits of the
      experimental techniques. Between the end of the 19th century and 1917, four plant
      biologists suggested that the filterable viruses were complex chemical substances
      rather than cellular microorganisms. Their contribution, not appreciated by the
      contemporary colleagues, laid the foundation of the modern concept of virus.

PMID- 14595903
TI  - Measure of species variability for a microbial taxonomy based on the relative
      resemblance.
AB  - The concept of species currently in use in microbial taxonomy is based on sex
      because derives from that developed in zoology and botany. The absence of sex as
      the only system to reproduce does not allow to use the hybridization as the test
      to assess the conspecificity of microbial strains, forcing microbial taxonomists
      to use relative resemblance among strains as the only tool to define microbial
      species and to classify new microorganisms. Relative resemblance can be
      intuitively defined as the situation in which two strains of the same species
      must be more similar than each of them with a strain of any other species.
      Unfortunately, there are several algorithms to define the similarity between two
      strains, but none can be used to estimate the average distance between several
      members of the same species. This paper describes the problems inherent with the
      definition of species without hybridization tests and proposes two algorithms for
      a standard estimation of the overall variability of a species with the data
      obtained from a sample of strains. These measures will allow the non-subjective
      determination of the overall similarity among members of the same species using
      results from both phenotypic and molecular analyses. Both algorithms are based on
      a bootsrapping procedure implemented by RHO and SMA, two software applications
      freely available from the internet. These applications allow an easy evaluation
      of parameters such as the overall variability and levels of confidence associated
      with the sample of strains and the panel of characters under study.

PMID- 14595902
TI  - Discrete-state theory in nerve impulse modelling.
AB  - Hodgkin-Huxley models have been the standard for describing ionic current
      kinetics. However, many single channel behaviors cannot be described using
      traditional Hodgkin-Huxley models; they can be described by expanding the Hodgkin
      Huxley models to have multiple resting and inactivated states. The model, based
      on charge translocation between a finite number of discrete Markovian states, is
      a biophysical kinetic model, according to current generalizations of channel
      structure, capable of reproducing channel behavior. The elaboration of the model
      is based on the Markov process. This type of model assumes that each channel has
      a discrete number of states that are connected by a kinetic diagram that defines
      the allowable transitions between these states and the rates at which these
      transitions occur. The application of the model presented here leads to results
      in accordance with the experimental data regarding the shape and characteristics
      of the nerve impulse registered along the nerve fibre. Unlike the traditional
      Hodgkin-Huxley models, the model based on the Markov processes has the advantage
      of removing the empirical equations, simplifying the computation of the membrane
      potential and revealing the single-channel variables. The average behavior is
      obtained by the repetition in one channel of the same stimulus, a number of times
      equal to the number of channels, which means that the macroscopic variables are
      predictable by the repetition, a certain number of times, of the same
      observations in a single channel.

PMID- 14595904
TI  - What is a role of the morphogens gradients in development?
AB  - The core idea of the gradient theory, a paradigm for developmental biology, is
      that biological morphogensis is based on a gradient-like distribution of a
      certain substance and its subsequent interpretation. This is an attempt at
      systematic criticism of this theory: I will argue that the experimental results
      do not support its core idea. Crucial in this context are the global reactions of
      an embryonic tissue upon chemical, genetic and mechanical manipulation and the
      possibility of regulation of the global and local events including redistribution
      of morphogens and de novo formation of the gene expression pattern. In addition
      to this, the possibility of other mechanisms should be explored.

PMID- 14595905
TI  - The microbial DNA cycle in soil.
AB  - Upon microbial cell death and lysis in soil, the free or naked DNA is exposed to
      the dynamic environment of the soil. The DNA can be enzymatically degraded by
      nucleases (DNases), bind to soil components, genetically transform competent
      bacterial cells and be a nutrient for other microorganisms. In this article we
      discuss the dual role of DNA as genetic material and as a nutrient source in the
      soil environment.

PMID- 14595906
TI  - Medium-term and long-term priorities in ecological studies.
AB  - Research priorities in ecology and environmental sciences for the future are
      formulated. The priorities for both fundamental and applied ecology are proposed.
      The list of priorities includes 50 items. The priorities are relevant to
      terrestrial, aquatic, and general ecology. The list of priorities is helpful when
      grant proposals are being prepared, evaluated, and selected for funding.

PMID- 14595907
TI  - Coming of age. As the Baby Boomer ages, long-term care must gear up for its own
      'boom'.

PMID- 14595908
TI  - Not an easy sell. Unlike previous generations, the Baby Boomer won't be as easy a
      draw to your long-term care facility.

PMID- 14595909
TI  - Broken and unsustainable. The aging of Baby Boomers means a cost crisis in long
      term care.

PMID- 14595910
TI  - Sales 'boom'. To turn Baby Boomer prospects into residents, sharpen your sales
      skills.

PMID- 14595911
TI  - A fresh mix. Meadow Lakes entices residents with a menu of lighter, healthier
      fare.

PMID- 14595912
TI  - The layering effect. Putting the Baby Boomers into proper perspective shows an
      evolving impact on senior living.

PMID- 14595913
TI  - New AADE tool a giant leap forward for diabetes education.

PMID- 14595914
TI  - Boost glycemic control in teen diabetics through 'family focused teamwork'.
AB  - While family conflict during the teenaged years is typical, it can have long-term
      health consequences when it involves an adolescent with diabetes. However,
      researchers at Joslin Diabetes Center in Boston have developed a low-cost
      intervention that aims to remove conflict from disease management
      responsibilities--and a new study shows that it can boost glycemic control as
      well.

PMID- 14595915
TI  - The new frontier: delivering cost-effective DM to rural populations.
AB  - It generally costs more to reach patients in outlying areas, but some pioneering
      organizations are getting around this barrier and, in fact, saving dollars by
      providing better care and preventive services to the chronically ill. Find out
      how two organizations have successfully addressed this challenge in dramatically
      different ways.

PMID- 14595916
TI  - Community-based model boosts BP control in high-risk population.
AB  - It's one of medicine's thorniest problems: We know how to treat high BP, but less
      than half of those with the condition are under adequate control. And the hardest
      hit populations are low-income, urban communities with high percentages of
      African American and Hispanic residents. A model developed at Johns Hopkins
      University is attacking the problem and has produced impressive results through
      the use of community health workers.

PMID- 14595918
TI  - Easier EH&S auditing.

PMID- 14595917
TI  - The hot work house.

PMID- 14595919
TI  - Report from VENT 2003.

PMID- 14595920
TI  - Scaffolding good practices.

PMID- 14595922
TI  - Envision an injury-free workforce.

PMID- 14595921
TI  - Keep your eye on the individual's visual function, Part 1.

PMID- 14595923
TI  - Tempering your emergency shower water ... because nobody likes a cold shower!

PMID- 14595924
TI  - Comparing eyewash systems.

PMID- 14595925
TI  - Solving hot work safety puzzles.

PMID- 14595926
TI  - Collapse, crash, or crime: who's missing?

PMID- 14595927
TI  - State-of-the-art monitoring.

PMID- 14595928
TI  - IH strategies in bad economic times.

PMID- 14595929
TI  - Psychosocial factors in IAQ crises.

PMID- 14595930
TI  - It's a matter of time.

PMID- 14595931
TI  - The road to deployment.

PMID- 14595932
TI  - Above & beyond BBS.

PMID- 14595933
TI  - Performance safety pays off.

PMID- 14595934
TI  - Chaplains can open eyes to bias.

PMID- 14595935
TI  - On coming to America.

PMID- 14595936
TI  - Legislation & regulation. The benefits of transparency.

PMID- 14595937
TI  - IT standards. Calling HHS.

PMID- 14595938
TI  - Community health. Everybody wins.

PMID- 14595939
TI  - Kids' care. Puttin' on a show.

PMID- 14595940
TI  - Disease management. Dual benefits.

PMID- 14595941
TI  - Practical ethics. Pay hike or CEO hikes.

PMID- 14595942
TI  - The data page. Outpatient revenue on the rise ... but profits don't follow.

PMID- 14595943
TI  - Community outreach. Battle of the bottle.

PMID- 14595944
TI  - Football in hospital land.

PMID- 14595945
TI  - By the numbers. Interview by Mary Grayson.
AB  - AHA chair-elect George Lynn predicts that health care reform will dominate the
      domestic policy debate in the upcoming presidential campaign. But this time
      around, he says, the debate should center on what we as a nation want in terms of
      health care before we address the question of how we pay for the agreed-upon
      services.

PMID- 14595946
TI  - Getting the attention of Big Pharma. And Big Pharma is listening.
AB  - Hospitals with social-service missions use their clout as shareholders to
      pressure drug companies to change policies on issues ranging from pricing to
      environmental concerns.

PMID- 14595947
TI  - 13th Annual Contract Management Survey.
AB  - Controlling costs is not the only catalyst for the increase in outsourcing by
      hospitals. The 13th annual survey shows that in some areas, outsourcing can
      affect patient satisfaction.

PMID- 14595948
TI  - Defining and refining women's health.
AB  - Competition from niche facilities, the rise of health care consumerism and
      breakthroughs in treatment are prompting hospitals to refocus their women's
      health programs.

PMID- 14595949
TI  - 2003 AHA Environmental Assessment.
AB  - The 2003 AHA Environmental Assessment highlights key market indicators that
      hospital leaders think will have the most influence on the health care climate
      over the next several years.

PMID- 14595950
TI  - At the ready. Hospital leaders shouldn't have to shoulder the burden of advocacy
      alone.

PMID- 14595951
TI  - Keep it local.

PMID- 14595952
TI  - Cold comfort.

PMID- 14595953
TI  - Less is more.

PMID- 14595954
TI  - Better than a cure.

PMID- 14595955
TI  - Ready for vaccination.

PMID- 14595956
TI  - Grumpy or depressed?

PMID- 14595957
TI  - Make Charlie proud.

PMID- 14595958
TI  - Prescribing change.

PMID- 14595959
TI  - Make a noise.

PMID- 14595960
TI  - Take time for you.

PMID- 14595961
TI  - Simply the breast.

PMID- 14595962
TI  - Creating a research culture in a nursing school.
AB  - BACKGROUND: Research in nursing schools still falls behind that in other
      disciplines. Schools need to develop a good research culture, in which those
      undertaking and supervising research are supported and guided. This requires
      commitment from management and effective leadership. CONCLUSION: To raise
      awareness the authors explore some of the ways in which a nursing school can
      foster a positive research environment.

PMID- 14595963
TI  - Total abdominal hysterectomy: development of a patient-centred care pathway.
AB  - This article describes how one organisation developed an integrated care pathway
      for women undergoing the procedure total abdominal hysterectomy. The efficacy of
      care pathways to provide patient-centred care is also discussed.

PMID- 14595964
TI  - Administration of medicines. Part 2: Pharmacology.
AB  - In the second part of this article, the authors examine the biological
      consequences for patients of changes in drug formulation, non-adherence to drug
      administration schedules and failure to accommodate drug/food interactions.

PMID- 14595965
TI  - Support system.

PMID- 14595966
TI  - [Intuitive knowledge in nursing care].
AB  - This is a qualitative study in a descriptive exploratory approach with the
      purpose to characterize the intuitive knowledge in nursing care. The qualitative
      data were generated through semi-structured interviews with 87 nursing
      professionals. The analysis of the data was done using QSR Vivo and interpreted
      through a framework based on studies of the North-American nursing literature.
      Intuition emerged as a feeling, as a type of knowledge, and as both. Further
      analysis showed three defining attributes: 1) knowledge of a fact or the truth,
      as a whole; 2) immediate possession of knowledge; 3) knowledge independent from
      linear reasoning process, as well as three types of intuition: cognitive
      inference, gestalt intuition, and precognitive function. The result of this study
      shows a parallel with the others found in North-American nursing literature.

PMID- 14595967
TI  - [The context of an emergency service: with the word, the user].
AB  - This article presents parts of a qualitative research of a "case-study" type.
      Through free observation, documents research and a non-structured interview the
      information was gathered. The purpose of this work was to become aware of the
      user's understanding of an emergency service, considering the environment and the
      way he/she was treated. The group of participants for this matter were in 12
      adults in which became inpatients after being examined at the emergency service.
      After analysing the data, the result was obtained and divided in the following
      categories: anything you need, go to the emergency service; that assessment; here
      everything is done; it isn't pleasant at all; I only have to thank.

PMID- 14595969
TI  - [Idealization and reality of nursing work at specialized units].
AB  - The research aimed at analyzing the nurse's work organization in specialized
      hospital sectors, and at knowing her conception about the activities in the
      clinical model of the health care. Through semi-structured interviews, it was
      found that activities change according to care complexity. The nurse has freedom
      of action in her routine, which is made in the interdependence relationship of
      health professionals. The articulating role developed by the nurse related to the
      physician's work and also to the other institution services was identified. It
      was confirmed that caring and managing are the nurse's work dimensions, which
      change according to the activities specification in the different specialized
      units.

PMID- 14595968
TI  - [Organ donation and bioethics: building an interface].
AB  - This study sought to identify the attitude of nursing undergraduate students
      concerning organ donation and their knowledge about the current law of organ
      donation. The last-year nursing undergraduate students from two Colleges in
      Goiania (GO) were approached. 45 students answered a questionnaire. A model of
      content analysis and bioethical principles was used to analyze the answers. The
      "Maintenance of the life" reveal willingness of subjects to donate organs to help
      others to stay alive. The "Unreliability" of health professionals for removing
      organs is associated to the feeling of great vulnerability. There is "Non
      Information" concerning the legislation in force. These results allow concluding
      that the donation of organs among subjects cannot be configured as an autonomous
      action.

PMID- 14595970
TI  - [Women and AIDS: breaking the silence in an adhesion group].
AB  - This study aims to discuss the relevance of the adhesion group on the quality of
      life of HIV-positive women who take part in that activity at a Centro Municipal
      de Saude (Rio de Janeiro--Brazil). It is a descriptive investigation with a
      qualitative approach. It focus on eight women infected by their steady partner.
      The theoretical referential is constituted by the categories of HIV/AIDS, gender
      and nursing care. The investigation evidences, as strategies to face AIDS, the
      increment of the Public Health System (SUS) and the Woman Integral Health Care
      Program (PAISM), the use of interdisciplinary approaches and multiprofessional
      critical methodologies in the implementation of health care. It is concluded that
      nursing care, in the context of the woman's health-disease process, must be ruled
      through the integrality of humanized assistance, attending ethical and solidarity
      principles and gender relationships.

PMID- 14595971
TI  - [Role of art at the Psychosocial Assistance Centers -- CAPS].
AB  - Study about the employment of the artistic approach in the cares developed at the
      CAPS. Founded on conceptual bases of Psychiatric Reform, the object of study has
      been broached by means of an exploratory field research through interview with
      CAPS's professionals. The results found indicate that activities with artistic
      basis are used by them aiming at a positive interaction with service users, and
      in the perspective of their psychosocial rehabilitation. We concluded that the
      work at the CAPS itself brings up-to-date creative potentialities of both
      professionals and users, being art assumed as an strategy of care.

PMID- 14595972
TI  - [Quality of life in coronary patients].
AB  - This study compared measures of quality of life (QOL) in two groups of coronary
      heart disease patients: one with myocardial infarction (MI) and one with angina
      (A). The population studied consisted of 49 patients from Group MI and 27
      patients from Group A. A questionnaire was used to identify socio-demographic and
      clinical data, as well as data from the SF-36 instrument, to assess the patients'
      QOL. It was observed in both groups that the QOI declined in the following
      aspects: physical functioning, pain, general health condition, vitality, social
      functioning, and mental health. Socio-demographic and clinical variables
      influenced the QOL score. Studies aiming at a larger number of individuals and a
      better understanding of the effects of the variables above upon the QOL of
      coronary patients are needed.

PMID- 14595973
TI  - [Practical knowledge in nursing training].
AB  - The study, carried through with nurses at the University Hospital Pedro Ernesto,
      looked to reflect on practical knowledge in the formation of the nurse. In the
      construction of the theoretical referential, the contributions of Patricia
      Benner, Phillipe Perrenoud and Donald Shon have been very relevant. From a
      methodological point of view, it consisted of a case study, with a qualitative
      approach; from semi-structured interviews with nurses involved in assisting the
      patient. The findings demonstrate that the competences that support the
      professional exercise are built on practical knowledge, theoretical knowledge,
      life experience, and professional socialization.

PMID- 14595974
TI  - [Violence and death by external causes].
AB  - An ecological study highlighted violence and death by external causes in Salvador
      and in Bahia through data furnished by the Fundacao Nacional de Saude (Health
      National Foundation) at the Ministerio da Saude (Ministry of Health), based on
      mortality records and population estimates by IBGE. The risk of death by homicide
      in Brazil is three times greater than in the United States, and up to forty times
      higher than in Japan. Homicide was the primary cause of loss of potential years
      of life (13.4%) in Brazil (1997), followed by traffic deaths (10.6%). External
      causes were the second cause of death in Salvador and Bahia (1996). Violence has
      cultural-social and political-ideological roots and it can be prevented by
      intersectional, multidisciplinary actions.

PMID- 14595975
TI  - [Outcome assessment methods in nursing care].
AB  - This review study aimed at the theoretical and methodological assessment of
      nursing care outcome. The study focused on the element outcome as a means to
      assess the nursing care service quality as well as on the nursing care
      classification and on the main methods and strategies used for assessing the
      outcome of nursing care, provided by health services.

PMID- 14595976
TI  - [Evidence-based practice: strategies for its implementation in nursing].
AB  - Evidence-based practice is an approach that enables the improvement of health
      care quality. The use of research findings on founded practice is one of the
      pillars of such approach; however, there are various barriers that hinder this
      nursing process, such as the lack of nurses' skills, lack of time and
      organizational support (human, material and financial resources). Therefore,
      based on the literature, this article presents some strategies that allow for the
      implementation of evidence-based practice in nursing in whatever area the nurse
      may perform.

PMID- 14595978
TI  - [Mental health: rebuilding knowledge in nursing].
AB  - The insane asylum, in spite of being criticized, reformed or even denied, is
      still a predominant habit in taking care of people with mental disturbances. That
      habit has as its basic principle the isolation of the mental sick, contradicting
      all the possibilities of assistance centered in an ethical humanism. This essay
      tries to interpret the institutionalization of the asylum, psychiatry, mental
      sickness and also the process of psychiatry reform, searching to contribute to
      all the reflections about uninstitutionalization, nursing knowledge and practice
      in mental health.

PMID- 14595977
TI  - [Nursing potentials in the management of health care].
AB  - In this article we intended to write an essay about the subjective questions that
      are at stake in the management of health care services by the nurse. So, we
      looked for elements in some of the studies developed about planning and
      administration, in the Sociology of Daily Life and also in the Feminist
      Theorization, related to health care management. We concluded that there is a
      need to improve the nurse's potentiality as a manager, starting with the referred
      theoretical perspectives, increasing the value of some aspects and feelings that
      have not been taken into consideration up to now in the time-space of health
      institutions, such as subjectivity, relationality, desire, creativity,
      responsibility, among others.

PMID- 14595979
TI  - [Nursing and pre-hospital care: dead-ends and perspectives].
AB  - The present paper is about a reflection related to the emerging of Pre-Hospital
      Care in Brazil ant its respective models of care during the last few decades. By
      drawing out a basic historical trajectory we were able to point out the
      successful and dead end paths of this modality of health assistance in our
      country. The most recent attempts of standardization at a national level of this
      kind of service were analyzed, especially the Health Ministry Decree no. 2048/02,
      which constitutes itself as a starting point, offering subsidies to institutions
      and to those involved in this specific field of health knowledge, in order to
      remake the path within another perspective.

PMID- 14595980
TI  - [Water, fires, and ethics. Tomorrow is always late].

PMID- 14595981
TI  - [Surgery in children and adolescents].
AB  - The authors explain in a standardized model of nursing care for children and
      adolescents durning pre-operative phase, the first part in the global surgical
      process. This phase commences at the moment a surgical intervention is deemed
      necessary and finalizes when the child/adolescent is transported to the operating
      room. The authors perform a systematic and holistic evaluation, using the Gordon
      Functional Health Patterns. Special emphasis is given to aspects such as the
      perception-management health pattern, the nutritional-metabolic pattern, the
      elimination pattern, the exercise-activity pattern, the dream-rest pattern, the
      self-perception pattern and the adaptation-stress tolerance pattern. They
      evaluate the perception and responses children of varying ages provide to being
      separated from parents. They highlight the cultural factors which must be born in
      mind in order to achieve an adequate evaluation and individualized care. The
      authors select the Nursing Diagnoses of NANDA, the North American Nursing
      Diagnosis Association, which most frequently appear in this pre-operative phase:
      fear/anxiety, risk of aspiration, risk of an alteration in health maintenance,
      and  risk of infection. Finally, the authors describe the nursinginterventions
      related with these diagnoses.

PMID- 14595982
TI  - [The VAMP device. Benefits for the critical patient].
AB  - Taking blood samples by means of conventional intravascular devices requires
      throwing away an initial volume of mixed blood and serum which comprises between
      24-26% of the volume of blood extracted from the patient admitted into an
      intensive care ward. At present time there exists a device with a reservoir,
      VAMP, which permits one to obtain blood samples without having to waste this
      initial volume. The working hypothesis poses that the use of the VAMP device
      decreases the risk of transfusion. This study has a random prospective design.
      This study subjects are 58 patients admitted in the intensive care ward at the
      Parc Tauli Corporation distributed in a control group which made use of a
      conventional device and a VAMP group which made use of the device having a
      reservoir. The study used a data recordsheet. Statistical calculations were
      carried out on the SPSS program.

PMID- 14595983
TI  - [Diabetic foot, a severe complication].
AB  - In this research project, the authors carried out a prospective descriptive study
      over a nine month period on 74 diabetic patients checked into the Vascular
      Surgery Ward at the Ramon y Cajal Hospital. The authors have compiled and
      analysed the diverse risk factors and variables which can bear an influence on
      this pathology; to do so, the authors collected the necessary data by means of a
      personal interview, medical records, analytical tests and readings as well as a
      direct inspection of the lesions. Among the results obtained, the authors
      emphasize the long average hospital stay, the poor control of their glycemia upon
      hospitalisation and the percentage of important ampulations these patients
      underwent; the authors were unable to corroborate other results present in
      articles consulted such as the relationship between the variables for years a
      patient had been suffering diabetes and the degree of the lesion on the Wagner
      scale.

PMID- 14595984
TI  - [Levonorgestrel. The day-after pill].
AB  - Only making use of Levonorgestrel as a post intercourse anti-conceptive method
      has proven to be more effective than prior methods and is the object under study
      in this report. This post intercourse anti-conceptive consists of a set of
      methods which, employed after at risk sexual intercourse and within a maximum
      period of time, avoid pregnancy. This post intercourse anti-conceptive is not
      considered to be an abortion method but it should not be used as a habitual anti
      conceptive method due to its adverse effects and its numerous interactions with
      other pharmaceutical products. Its use shall be limited to emergency situations.
      Special emphasis must be given as part of health education to females who employ
      this technique. As health professionals, we need to know this topic in depth so
      that we can best advise those persons in need of information. The authors propose
      to provide general information about aspects related to this pharmaceutical
      product.

PMID- 14595985
TI  - [Myths, challenges, and fallacies in nursing research].
AB  - Upon the completion of 25 years of the integration of Nursing in the Spanish
      University system, this author presents a reflection on the role of research in
      nursing professional development and the consolidation of nursing as a university
      field. After tearing down the negative mythology which surrounds research in
      nursing, the author develops what he considers are the three main challenges at
      the start of this new millennium: to make visible the potential researchers in
      the field of Nursing, construct Nursing by manes of research, and utilize
      research as a method to emancipate Nursing. At the end of his article, the author
      proposes using the critical spirit which develops during a research exercise in
      order to think critically about the system, with a goal to adopt an intellectual
      compromise to provide scientifically valid response to the contradictions in the
      hegemonic medical system, favoring the democratization of health care.

PMID- 14595986
TI  - [Gastrostomy and nutrition. Nursing care].
AB  - The article refers to the nursing treatment required when using a gastrostomy to
      administer enteral nutrition, mainly for children. Emphasis is placed on the
      attention to parents, since they are the ones who will apply this treatment. The
      author analyses the cures for a stoma, external support mechanisms and possible
      complications that may arise along with solutions for them.

PMID- 14595988
TI  - [Surgery of superficial skin injuries (I of III). Nursing approach].
AB  - Among the procedures in minor surgery, to suture wounds is a technique which
      nursing professional frequently perform as part of their normal work load,
      especially those nurses who work in Primary Health Care Centers and Emergency
      Wards. This article in the first in a series of three articles which enables the
      reader to review his/her knowledge about how to repair superficial skin lesions.
      After citing the legal aspects, the authors shall review each step in this
      procedure. We will check to see if the indication for suture is correct,
      evaluating a wound adequately. Afterwards, we review the procedure to clean the
      wound and to apply an anti-tetanus prophylaxis. We will mention how to adequately
      select the technique, the suture material and the instrument to be used. We will
      show the manner to use to avoid complications derived from an inadequate
      technique and we will continue with the follow up procedure for cicatrisation
      after first treatment, which includes informing the patient and a precocious
      treatment of complications, assuring the patient's welfare and the defense of
      his/her rights at all times; all of which will make possible an intervention
      which guarantees quality and is satisfactory to both the patient and the nursing
      professional who employs it.

PMID- 14595987
TI  - [Surgical field. Polyvalent or specialized nursing: job satisfaction and quality
      of care].
AB  - This article focuses on study about nursing staff working satisfaction in a
      Surgical Ward as well as determining the difference, if this difference exists,
      in the degree of staff satisfaction among those whose work is performed as a
      specialist or a polyvalent nurse. A specialist is defined as a person who carries
      out his/her professional duties in the same surgical ward over two years or more;
      a polyvalent nurse is defined as one who changes their specialty according to the
      period established by their hospital or according to the needs at any given
      moment.

PMID- 14595989
TI  - [Alcoholism].

PMID- 14595990
TI  - [Guidelines for nursing methodology implantation].
AB  - The authors introduce three guidelines as part of the process to implant the
      nursing methodology based on the Virginia Henderson Conceptual Model; they
      propose to help nurses adopt the aforementioned method in their daily practice.
      These three guidelines shall be published in successive articles: Guidelines to
      identify attitudes and aptitudes related to the nursing profession; Guidelines to
      implant the nursing methodology based on the Virginia Henderson Conceptual Model;
      and Guidelines to plan areas for improvement.

PMID- 14595991
TI  - The female athlete triad. A growing health concern.
AB  - The number of female athletes participating at the high school, collegiate, and
      elite levels has increased nearly 10-fold since the passage of Title IX.
      President Nixon signed title IX into law in 1972. It required that all schools
      receiving federal funding provide equal opportunities for men and women. With
      this large increase in high-level female athletes comes a special set of medical
      and orthopaedic issues. One of the most important is the female athlete triad.
      The triad consists of disordered eating, amenorrhea, and premature osteoporosis.
      Currently, this problem is largely unrecognized. The purpose of this article is
      to help to educate orthopaedic nurses about this important issue so that we can
      detect the triad early and help address this growing national health issue.

PMID- 14595993
TI  - Changing career paths. From expert to novice.
AB  - In today's changing healthcare environment, career paths are also changing.
      Healthcare workers are faced with new and unfamiliar territory. Experts are now
      faced with the same feelings they had as novices. By reviewing the stages of
      skill acquisition, novice, advanced beginner, competent, proficient and expert,
      healthcare professionals will be able to cope with those feelings of uncertainty.
      A review of some coping strategies will ease the transition to a new career path.

PMID- 14595992
TI  - Patients with eating disorders. A high-risk group for fractures.
AB  - PURPOSE: To analyze fracture risk and bone mineral density in patients with
      eating disorders (anorexia nervosa, bulimia nervosa, and other eating disorders).
      DESIGN: Clinical overview. FINDINGS: Bone mineral density is decreased and
      fracture risk increased in patients with anorexia nervosa. In patients with
      bulimia nervosa, bone mineral is only marginally decreased and fracture risk
      marginally increased. In patients with other eating disorders (eating disorders
      not otherwise specified), bone mineral density is decreased and fracture risk
      increased. CONCLUSIONS: Fracture risk is increased in patients with eating
      disorders. An eating disorder should be suspected in severely underweight young
      individuals (primarily girls) presenting with fractures, especially low-energy
      fractures.

PMID- 14595994
TI  - Alternative therapies for arthritis treatment. Part 1.
AB  - Because conventional treatment options focus mostly on pain management, an
      increasing number of the 43 million people with arthritis are seeking alternative
      methods of disease management to improve their quality of life. According to a
      1998 survey (Eisenberg et al., 1998), those who have used alternative methods to
      manage their diseases are included in the 50% of Americans who have tried an
      alternative treatment modality. As the first in a two-part series, this article
      reviews the historical use of selected alternative therapies and provides current
      information that will help orthopaedic nurses and other healthcare providers to
      advise their patients on the use of such treatment modalities.

PMID- 14595995
TI  - Traumatic shoulder instability. Nonsurgical management versus surgical
      intervention.
AB  - Shoulder instability is classified as either traumatic or atraumatic based on the
      mechanism of injury. Traditional treatment for both forms of instability involves
      a nonsurgical approach, consisting of immobilization, rehabilitation, and a delay
      in the return to vigorous activities. This treatment is often quite successful in
      preventing recurrent dislocations in the patient with atraumatic instability.
      However, those patients with traumatic instability often experience further
      dislocations or subluxations, with recurrence rates as high as 94% in patients
      younger than 20 years. These recurrent episodes of instability can result in
      injuries to the capsulolabral structures (Bankart lesions), humeral head (Hill
      Sachs defect), and neurologic structures. Open surgical reconstructions for
      anterior instability have been reported to be 94-100% successful in preventing
      recurrence. Arthroscopic stabilization procedures are successful in preventing
      recurrence in 80-90% of patients and result in low morbidity. However, the most
      common form of initial treatment for traumatic anterior shoulder instability
      remains immobilization, supervised rehabilitation, and gradual return to full
      activity, despite significantly inferior results when compared to operative
      intervention. This article addresses the treatment options available to the nurse
      practitioner when managing the patient with traumatic anterior instability.

PMID- 14595996
TI  - Effects of T'ai Chi exercise on fibromyalgia symptoms and health-related quality
      of life.
AB  - BACKGROUND: Fibromyalgia (FM), one of the most common musculoskeletal disorders,
      is associated with high levels of impaired health and inadequate or limited
      symptom relief. The cause of this complex syndrome is unknown, and there is no
      known cure. Numerous research results indicate that a combination of physical
      exercise and mind-body therapy is effective in symptom management. T'ai Chi, an
      ancient Chinese exercise, combines physical exercise with mindbody therapy.
      PURPOSE: To investigate the effects of T'ai Chi exercise on FM symptoms and
      health-related quality of life. DESIGN: Pilot study, one group pre-to-post
      posttest design. METHODS: Participants with FM (n = 39) formed a single group for
      6 weeks of 1-hour, twice weekly T'ai Chi exercise classes. FM symptoms and health
      related quality of life were measured before and after exercise. FINDINGS: Twenty
      one participants completed at least 10 of the 12 exercise sessions. Although the
      dropout rate was higher than expected, measurements on both the Fibromyalgia
      Impact Questionnaire (FIQ) (Buckhardt, Clark, & Bennett, 1991) and the Short Form
      36 (SE-36) (Ware & Sherbourne, 1992) revealed statistically significant
      improvement in symptom management and health-related quality of life.
      IMPLICATIONS FOR NURSING RESEARCH: Knowledge of interventions to enhance health
      for the patient with musculoskeletal problems is a National Association of
      Orthopaedic Nurses priority. Tai Chi is potentially beneficial to patients with
      FM. Further research is needed to support evidence-based practice.

PMID- 14595997
TI  - Tired blood. Part 2.
AB  - Anemia, "tired blood," with all the accompanying symptoms, such as fatigue,
      dyspnea, dizziness, muscle weakness, altered brain function, decreased
      gastrointestinal function, and cardiac stress, is not a disease. Rather, anemia
      is a sign that something has interfered with the red blood cell transport system
      that carries hemoglobin-containing oxygen to all bodily tissues (National Anemia
      Action Council [NAAC], 2002). In part 1 of this discussion (May/June issue of
      Orthopaedic Nursing), anemias related to interference with red blood cell
      development were addressed. In this section, anemias related to hemoglobin
      abnormalities (microcytic hypochromic anemia) and anemias related to premature
      erythrocyte destruction (hemolytic anemia) are discussed. Treatment approaches
      and selected pharmacological interventions are identified.

PMID- 14595998
TI  - The UniSpacer for knee osteoarthritis.

PMID- 14595999
TI  - Oxygen vacancy: the invisible agent on oxide surfaces.

PMID- 14596000
TI  - Structural forces near phase transitions of liquid crystals.
AB  - The structure of the fragile liquid-crystalline phases has a strong impact on the
      forces between bodies immersed in a liquid crystal (LC). We have equipped an
      atomic force microscope with a precise temperature control and measured various
      liquid-crystalline structural forces at temperatures close to the phase
      transitions. The observed forces agree well with predictions of Landau--de Gennes
      phenomenological theory of LCs, even at a nanoscale length. In addition to this,
      we have observed a molecular layer, adsorbed on the surfactant-covered glass
      surface, and determined its thickness and elastic properties.

PMID- 14596001
TI  - Electric-field-induced capillary attraction between like-charged particles at
      liquid interfaces.

PMID- 14596002
TI  - Locating dynamic species with X-ray crystallography and NMR spectroscopy: acetone
      in p-tert-Butylcalix[4]arene.
AB  - The exact location and orientation of dynamic species in structural studies
      continues to be a serious challenge, yet it is of paramount importance in
      modeling guest--host interactions so as to improve our understanding of the
      multiple weak interactions that govern many chemical and biological processes.
      The acetone guest in the tBC (p-tert-butylcalixarene) host presents such a
      challenge, as initial guest positions obtained from single crystal X-ray
      diffraction (XRD) are incompatible with the 2H NMR spectrum. A detailed
      consideration of the diffraction data showed that more complicated structural
      models could be constructed that were consistent with the NMR data and still
      yielded satisfactory diffraction residuals. These models agree that one acetone
      methyl group is inserted into the deep cavity, and that it exchanges with the
      second methyl group outside. The outside methyl group in turn can switch
      positions with the carbonyl group, but the distribution of the methyl and
      carbonyl groups over the two sites is not equal. One factor that poses additional
      difficulty in deciding between models is whether the actual space group is
      tetragonal (P4/n), or twinned monoclinic (P2/n). All of the structural models
      considered here disagree substantially with the one proposed in an earlier
      publication.

PMID- 14596003
TI  - Micelle and solvent relaxation in aqueous sodium dodecylsulfate solutions.
AB  - Dielectric spectra have been measured for aqueous sodium dodecylsulfate (SDS)
      solutions up to 0.1 mol L-1 at 25 degrees C over the frequency range 0.005 < or =
      nu GHz-1 < or = 89. The spectra exhibit two relaxation processes at approximately
      0.03 GHz and 0.2 GHz associated with the presence of micelles in addition to the
      dominant solvent relaxation process at approximately 18 GHz and a small
      contribution at approximately 1.8 GHz due to H2O molecules hydrating the
      micelles. Detailed analysis reveals that the micelles bind 20 water molecules per
      SDS unit, but not as strongly as trimethylalkylammonium halide surfactants do.
      The relaxation times and amplitudes of both micelle relaxation processes can be
      simultaneously analysed with the theory of Grosse, yielding the effective volume
      of a SDS unit in the micelle and the lateral diffusion coefficient of the bound
      counterions. The findings of this investigation fully corroborate recent
      molecular dynamics simulations on structure and dynamics of SDS micelles.

PMID- 14596004
TI  - Anchoring Fe ions to amorphous and crystalline oxides: a means to tune the degree
      of Fe coordination.
AB  - We report on an IR spectroscopic study on the room-temperature adsorption of NO
      on different iron(II)-containing siliceous matrices. Fe2+ hosted inside the
      channels of MFI-type zeolites (Fe-ZSM-5 and Al-free Fe-silicalite) exhibits
      pronounced coordinative unsaturation, as witnessed by the capability to form, at
      300 K, [Fe2-(NO)], [Fe2+(NO)2] and [Fe2+(NO)3] complexes with increasing NO
      equilibrium pressure. Fe2+ hosted on amorphous supports (high surface area SiO2
      and MCM-41) sinks more deeply into the surface of the siliceous support and thus
      exhibits less pronounced coordinative unsaturation: only [Fe2+(NO)2] complexes
      were observed, even at the highest investigated NO equilibrium pressures.
      Activation at higher temperature (1073 K) of the Al-free Fe-silicalite sample
      resulted in the appearance of Fe2+ species similar to those observed on SiO2 and
      MCM-41, and this suggests that local (since not detectable by X-ray diffraction)
      amorphisation of the environment around Fe2+ anchoring sites occurs. The fact
      that this behaviour is not observed on the Fe-ZSM-5 sample activated at the same
      temperature suggests that framework Al species (and their negatively charged
      oxygen environment) have an important role in anchoring extraframework Fe2+
      species. Such an anchoring phenomenon will prevent a random migration of iron
      species, with subsequent aggregation and loss of coordinative unsaturation. These
      observations can thus explain the higher catalytic activity of the Fe-ZSM-5
      system in one-step benzene to phenol conversion when compared with the parent, Al
      free, Fe-silicalite system with similar Fe content. The nature of the support and
      the activation temperature can therefore be used as effective means to tune the
      degree of Fe coordination.

PMID- 14596005
TI  - Excited-state proton-relay dynamics of 7-hydroxyquinoline embedded in a solid
      matrix of poly(2-hydroxyethyl methacrylate).
AB  - Excited 7-hydroxyquinoline embedded in a solid matrix of poly(2-hydroxyethyl
      methacrylate) undergoes a proton-relay reaction efficiently to form its keto
      tautomer. However, the reaction mechanism depends on the torsional conformation
      and the microscopic environment of the molecule at the moment of excitation.
      Whereas the bridged cis-enol form undergoes proton relay immediately on
      absorption of a photon to produce its tautomeric keto species, the unbridged cis
      form requires 120 ps for bridge formation via solvent reorganization prior to
      proton relay. Furthermore, the trans form needs 1000 ps for tautomerization
      because it requires an activated (11 kJ mol-1) torsional motion to change into
      its cis form prior to bridge formation and proton relay. Torsional motion rather
      than solvent reorganization determines the proton relay rate of the trans-form of
      the molecule.

PMID- 14596006
TI  - A theoretical study of the UV/visible absorption and emission solvatochromic
      properties of solvent-sensitive dyes.
AB  - Using the density-functional vertical self-consistent reaction field (VSCRF)
      solvation model, incorporated with the conductor-like screening model (COSMO) and
      the self-consistent reaction field (SCRF) methods, we have studied the
      solvatochromic shifts of both the absorption and emission bands of four solvent
      sensitive dyes in different solutions. The dye molecules studied here are: S-TBA
      merocyanine, Abdel-Halim's merocyanine, the rigidified amino-coumarin C153, and
      Nile red. These dyes were selected because they exemplify different structural
      features likely to impact the solvent-sensitive fluorescence of "push-pull", or
      merocyanine, fluorophores. All trends of the blue or red shifts were correctly
      predicted, comparing with the experimental observations. Explict H-bonding
      interactions were also considered in several protic solutions like H2O, methanol
      and ethanol, showing that including explicit H-bonding solvent molecule(s) in the
      calculations is important to obtain the correct order of the excitation and
      emission energies. The geometries, electronic structures, dipole moments, and
      intra- and intermolecular charge transfers of the dyes in different solvents are
      also discussed.

PMID- 14596008
TI  - Photoinduced reduction of silver inside microscale polyelectrolyte capsules.

PMID- 14596007
TI  - Nanoscopic structure of a metallo-supramolecular polyelectrolyte--amphiphile
      complex, elucidated by X-ray scattering and molecular modeling.
AB  - A combination of molecular modeling and X-ray scattering was used to elucidate
      the structure of the metallosupramolecular polyelectrolyte--amphiphile complex
      (PAC) self-assembled from FeII, 1,4-bis(2,2':6,'2"-terpyridin-4'-yl)benzene, and
      dihexadecyl phosphate (DHP). An approximate structure of the semi-ordered
      material was derived from the analysis of the X-ray scattering data. The
      experimental data provided sufficient input for obtaining a useful starting
      configuration for molecular modeling. Various models of the supramolecular
      architecture are presented and discussed in terms of their total energies and
      scattering patterns. In an iterative approach each level of the structural
      hierarchy was refined until satisfactory agreement of calculated and experimental
      scattering patterns was reached. The remarkable sensitivity of the simulated
      scattering curves to even the smallest structural changes at all length scales
      restricts the arbitrariness of modeling. The final model of PAC consists of flat
      lamellae of alternating strata of interdigitated DHP monolayers and nematically
      ordered polyelectrolyte chains.

PMID- 14596009
TI  - Silicon-on insulator based thin-film resistor for chemical and biological sensor
      applications.

PMID- 14596010
TI  - Influence of molecular arrangement in self-assembled monolayers on adhesion
      forces measured by chemical force microscopy.

PMID- 14596011
TI  - The case of the disappearing monolayer: alkylsilane monolayer formation,
      oxidation, and subsequent transparency to scanning tunneling microscopy.

PMID- 14596012
TI  - Assembling nanometer nickel particles into ordered arrays.

PMID- 14596013
TI  - Functional polymeric micelles formed from a novel cationic star block copolymer.

PMID- 14596015
TI  - Multifrequency photochromic recording and nondestructive readout using IR light.

PMID- 14596014
TI  - Photon counting histogram for one-photon excitation.

PMID- 14596016
TI  - Experimental detection of the H2NO3 radical.

PMID- 14596017
TI  - [Reactive macrophage activation syndrome].
AB  - Reactive macrophage activation syndrome or haemophagocytic lymphohistiocytosis is
      a life-threatening immunoregulatory disorder characterized by the activation of
      the mononuclear phagocytic system with prominent haemophagocytosis particularly
      involving the bone marrow, reticuloendothelial system and central nervous system.
      It frequently occurs in children as a familial autosomal recessive disorder and
      it has been reportedly associated with infections, underlying hematopoetic
      malignancies or autoimmune disorders. It has been suggested that central to the
      pathogenesis of this disorder is uncontrolled T-cell activation which results in
      the excessive secretion of cytokines. The clinical and laboratory findings are
      dramatic, at presentation with persistent fever, hepatosplenomegaly, profound
      depression of three blood cell lines, elevated serum liver enzyme values,
      coagulopathy and abundant haemophagocytosis can be visualized in bone marrow.
      Most of the described clinical findings could be explained by the oversecretion
      of proinflammatory cytokines and the presence of histiocytic infiltrates. In
      general, immunosuppressive therapy, cytotoxic chemotherapy with immunomodulatory
      agents will induce remissions in a substantial percentage of patients, whereas
      others require allogenic bone marrow transplantation.

PMID- 14596018
TI  - [Pharmacologic treatment of benign prostatic hyperplasia].
AB  - Medical treatment for benign prostatic hyperplasia is reviewed by the author.
      Experiences with herbal extracts have been known for more than 2 decades.
      Treating benign prostatic hyperplasia with these extracts are recommended in
      initial phase. Effectiveness of these drugs are approved by some placebo
      controlled double blind studies. However effectiveness of these are not as good
      as medical drugs'. It is well known that they have no side effects and are
      cheaper than medicines. Prostate volume is decreased and mechanical component of
      dysuria is improved by treating for long time (months, years) with 5 alfa
      reductase finasterid which contain hormone. This drug is indicated when volume of
      the prostate is over 40 g. Dynamical component of benign prostatic hyperplasia is
      treated with a receptor blockers which act on the bladder neck. These medicines
      effect earlier and are recommended for all benign prostatic hyperplasia patients
      independently of prostate volume. These might have some side effect like
      hypotension.

PMID- 14596019
TI  - [Molecular genetic methods in anaplastic large cell lymphoma].
AB  - INTRODUCTION: Anaplastic large cell lymphoma belongs to a relatively good
      prognostic group of high grade non-Hodgkin lymphomas. Molecular genetic methods
      can provide great help in the differential diagnosis of the disease. AIMS:
      Sixteen frozen lymph node samples of CD30 positive lymphomas with anaplastic
      morphology and 1 bone marrow aspiration were analysed with polymerase chain
      reaction according to T-cell receptor gene and immunglobulin heavy chain gene
      rearrangement. T(2;5)(p23;q35), t(1;2)(q25;p23) chromosomal translocation was
      also investigated with reverse transcriptase polymerase chain reaction. RESULTS:
      Seven cases showed null-, 3 T-, 4 B- and 2 T/B hibrid genotype. Two cases of
      t(2;5), whereas no t(1;2) translocation was demonstrated. CONCLUSIONS: Molecular
      genetic results correlated with the results of immunhistochemistry and can give
      further help to divide the cases into smaller, new prognostic subgroups.

PMID- 14596020
TI  - [Epidemiology of inflammatory bowel diseases in Veszprem county of Western
      Hungary between 1977 and 2001].
AB  - INTRODUCTION: An epidemiological study of inflammatory bowel disease (IBD) in
      Veszprem county (located in western part of Hungary) was carried out from 1977 to
      2001. METHODS: Both hospital and outpatient records of IBD patients were
      collected reviewed carefully. Most patients have been followed up regularly.
      RESULTS: The number of population has decreased during the observed period from
      386,000 to 376,000. The county has both industrial and agrarian parts. 560 new
      ulcerative colitis (UC) cases, 212 Crohn's disease (CD), and 40 indeterminate
      colitides (IC) were diagnosed in the investigated period. Incidence rate
      increased from 1.66 (1977-1981) to 11.01 (1997-2001) in UC, and from 0.41 to 4.68
      in CD, respectively. The incidence rate in IC rose from 0.26 to 0.74. The M/F
      ratio in UC was 1.06, in CD: 1.03, respectively, 41 UD patients and 13 CD
      patients died, the cause of death was disease related in 6 UC and in 6 CD
      patients. The average age at death in UC was not different from that observed in
      general population (66.4 years) but in CD (50.1 years) it was much earlier. The
      disease related mortality was low, 0.06/100,000 both in UC and CD. The prevalence
      rate at the end of 2001 was 142.6 for UC and 52.9/100,000 inhabitants for CD.
      Mean age at onset in UC was 38.9 +/- 15.5 years, in CD 31.7 +/- 12.8 years. We
      observed only one peak onset of the diseases, in UC it was between 30 and 40
      years, in CD between 20 and 30 years. People living in towns were more liable to
      acquire the disease (ORUC = 1.27, ORCD = 1.13). The rate of smokers at the onset
      was 14.3% (OR = 0.25) in UC and 50.5% (OR = 1.98) in CD. Ex-smokers were 18.4%
      and 6.4%. Family history of IBD was present in 3.4% in UC and 9.9% in CD. The
      location of UC (according to the known largest extent) was proctitis in 112
      cases, proctosigmoiditis in 162 cases, left sided colitis in 117 and subtotal or
      pancolitis in 169 cases. The location of CD was only ileal in 68 cases,
      ileocolonic in 87 cases, colonic in 57 cases. The behaviour of CD was non
      stricturing-non-penetrating in 63 cases, stricturing in 54 cases, penetrating in
      95 cases. 59.4% of the CD patients had at least one operation, 6.1% had more than
      3 operations. CONCLUSION: The incidence and prevalence rates have increased
      steadily in Veszprem County, now it reaches that of most western European
      countries. There were no gender differences either in UC or CD. Smoking seemed to
      be a risk factor for CD, but it was preventive for UC. The rapid increase in
      incidence supports a role for environmental (e.g. diet, lifestyle changes) risk
      factors.

PMID- 14596022
TI  - [Therapy of functional dyspepsia].

PMID- 14596021
TI  - [Therapy resistant leg ulcer caused by multiple myeloma].
AB  - The authors review an elderly woman suffering from leg ulcer with bad curability
      which was a consequence of a malignant haematologic disease. Multiple relapse of
      this ulcer was observed and did not react to usual conservative therapy. The only
      sign of multiple myeloma was the extremely high level of iron measured in the
      blood serum bound to a monoclonal paraprotein. Sternum aspiration was made and
      the sample showed presence of plasmoblasts supporting diagnosis of multiple
      myeloma. The poor therapeutical results were caused by hyperviscosity syndrome in
      consequence of the high level of the monoclonal component in the blood serum. The
      ulcer was cured within eight weeks by suppression of the monocloclonal component
      and thus, elimination of hyperviscosity. This case is a special one from several
      points of view. Leg ulcers not reacting to usual therapy may be caused by
      haematologic disease thus the physician should consider this and extend
      examinations as well and necessarily hospitalize patient. Appearance of multiple
      myeloma is unusual in this case. Hystology made from the skin excised from the
      periphery of the wound has not showed signs of pyoderma gangrenosum, which is
      known mostly being associated with multiple myeloma.

PMID- 14596023
TI  - [Etiopathogenesis of inflammatory bowel diseases].
AB  - The pathogenesis of IBD is only partly understood; various environmental and host
      (e.g. genetic-, epithelial-, immune and non-immune) factors are involved. It is a
      multifactorial polygenic disease with probable genetic heterogeneity, some genes
      are associated with IBD itself, while others increase the risk of ulcerative
      colitis (UC) or Crohn's disease (CD) or are associated with disease location
      and/or behaviour. The role of environmental factors, in particular, enteric
      antigens, smoking and non-steroid anti-inflammatory drug use has been well
      established. However uptil now no proof of a role of any unique pathogenic
      bacteria or special dietary and/or psychosocial factor has been identified. In
      this hypothesis, the disease may develop in a genetically predisposed host as a
      consequence of disregulated immune response to environmental, in particular,
      enteric antigens, resulting in a continuous immune-mediated inflammation (in CD
      predominantly Th-1, in UC a modified Th-2 mechanisms are involved) and not in
      tolerance. As a consequence, the permeability of mucosa and the antigen challenge
      increases, in contrast, the disregulated immune response is unable to
      downregulate the inflammatory process. This will result in a continuous
      inflammation and tissue damage. The pathogenesis of CD is thought to be mainly an
      antigen driven, T-lymphocyte dependent process, while in UC the role of
      epithelial factors and activated granulocytes are essential.

PMID- 14596024
TI  - [Cardiologic and diabetologic aspects of therapy with angiotensin receptor
      blocking agents].
AB  - Authors based on studies fullfiling the principles of evidence based medicine
      review the efficiency and benefits of angiotensin receptor blocking agents in
      congestive heart failure and hypertension. Special attention is focused on their
      application in diabetes mellitus. The data support efficacy, good tolerability,
      beneficial side effect profile as well as cardio- and renoprotective properties
      of these drugs. Their safety in diabetic as well as and in non-diabetic persons
      can be underlined.

PMID- 14596025
TI  - [Month of birth in childhood acute lymphoblastic leukemia].
AB  - INTRODUCTION: An association between date of birth influenced by certain
      environmental factors (such as virus infections) and malignant diseases has been
      suggested in some previous papers. AIMS AND METHODS: The authors analyzed the
      birth dates of 814 children, 0-18 years of age, in whom acute lymphoblastic
      leukemia was diagnosed in the period between the 1st of January 1988 and 31st of
      December 2000. RESULTS: No association between month of birth and manifestation
      of leukemia in Hungarian children could be established. CONCLUSION: The results
      suggest that this approach was not capable of detecting any obvious prenatal
      environmental factors, including virus endemics, that could have influenced the
      appearance of leukemia.

PMID- 14596026
TI  - [Immunobiology of dendritic cells and their application in clinical practice].
AB  - INTRODUCTION: Dendritic cells play a central role in the regulation of the immune
      responses towards cellular or humoral immunity. Several types of dendritic cells
      can be distinguished, which originate from different hematopoietic lineages, and
      differ from each other in function, morphology and localization within the
      organism. Immature dendritic cell-precursors originate from bone marrow
      haemopoietic stem cells, circulate in blood system and reach peripheral tissues,
      where they differentiate into active antigen capturing and processing cells. They
      have further maturation by the effect of adequate signals (antigen stimuli and
      inflammatory cytokines) and migrate into secondary lymphoid organs, presented
      cell surface MHC molecules-linked peptides from antigens which they have captured
      and processed, to T lymphocytes, induce immune reaction by T cell activation.
      Apart from the fact that dendritic cells as professional antigen presenting cells
      are essential to induction T cell-mediated immune responses, they influence
      activation and function of B lymphocytes and effector cells of natural immune
      system by cytokines and cell-cell interactions. CONCLUSIONS: Complex regulatory
      function of dendritic cells make a possibility for artificial alteration of
      immune processes by modification of dendritic cells: direct against definitive
      antigens, increase or decrease their intensity, hereby we can accomplish the
      immunotherapy of different diseases such as tumors, infection, autoimmune
      diseases, transplants' rejection.

PMID- 14596027
TI  - [Therapy of upper respiratory tract infections (acute tonsillopharyngitis, acute
      rhinosinusitis, acute otitis media)].

PMID- 14596029
TI  - [Centenary of the building of Mercy Hospital in Buda].

PMID- 14596028
TI  - [Therapy of acute pancreatitis].

PMID- 14596030
TI  - [Obesity in women].
AB  - Obesity has become an important problem of public health in all developed
      countries. It has slightly different connotations in women because, apart from
      its greater prevalence, low socio-economic level is a risk factor solely for
      women. As well as a cardiovascular risk factor in women, it is associated with an
      increased risk of breast cancer, cancer of the endometrium, ovarian polycystosis
      and infertility. Weight control in women has a large aesthetic motivation and
      eating has considerable emotional components. On the other hand, women consume
      more drugs (contraceptives, painkillers, migraine treatments, anxiolytics, anti
      depressants) which seem to favour obesity. The role played in the pathogenesis of
      obesity by cyclical hormonal changes, pregnancy, the consumption of oral
      contraceptives and the menopause remains to be clarified. The effect of
      replacement hormone therapy as a cause of weight gain is doubtful.

PMID- 14596031
TI  - [Pretreatment dysphagia in patients with advanced head and neck cancer].
AB  - OBJECTIVE: To define swallowing dysfunctions in head and neck cancer patients
      with respect to tumor site. PATIENTS AND METHODS: A consecutive cohort of 52
      patients with stage III-IV head and neck cancer without prior tracheotomy or
      treatment were studied according to tumor site: oral cavity (n = 8), oropharynx
      (n = 8), hypopharynx (n = 13) and larynx (23). All patients underwent
      nasoendoscopy prior to treatment. Swallowing function (dysphagia, aspiration and
      Swallowing Performance Status Seale score) was analyzed with reference to tumor
      localization using chi 2 and Fisher exact tests. RESULTS: Laryngeal and
      hypopharyngeal neoplasms neoplasms showed the most severe pre-treatment
      swallowing dysfunction (27% pre-treatment vs. 11% post-treatment), and oral and
      oropharyngeal neoplasms showed the most severe post-treatment swallowing
      dysfunction (6% pretreatment vs. 68% post-treatment). Aspiration and tumor
      localization revealed not statistically significant differences between groups.
      Pre-treatment dysphagia did not correlate with post-treatment dysphagia.
      CONCLUSIONS: Laryngeal and hypopharyngeal neoplasms showed severe pre-treatment
      swallowing dysfunctional and oral and oropharyngeal neoplasms showed severe post
      treatment swallowing dysfunction.

PMID- 14596032
TI  - [Postoperative nutrition in patients with head and neck cancer].
AB  - Patients who underwent surgery for head and neck malignant neoplasms are
      problematic because dysphagia, pain and postoperative secuelaes. Nutritional
      support is necessary in more than 90% of all patients with head and neck cancer.
      The purpose of this study is to determine nutritional support in these patients
      and problems related to nutrition. METHODS: Fifty-four patients with oral and
      pharyngolaryngeal carcinomas underwent surgery were studied prospectively. We
      studied nutritional support (oral nutrition, enteral nutrition or parenteral
      nutrition) and problems related to nutrition: aspiration neumoniae and
      pharyngostoma. RESULTS: The 7% of the patients underwent oral feeding after
      surgery, 87% enteral nutrition with nasogastric tube and 6% parenteral nutrition.
      We identified neumoniae in 6% of patients and faringocutaneous fistula in 19%.
      When patients leaved the hospital, 98% of the patients underwent oral feeding and
      one patient had nasopharyngeal tube for enteral nutrition. CONCLUSIONS: 1.
      Artificial nutrition was necessary in 93% patients with
      oropharyngolaryngealcancer; 2. Enteral nutrition was the most useful modality of
      alimentation (87%); 3.25% of patients had postoperative complications: (18%
      pharyngostoma, 6% neumoniae); 4. Oral feeding was possible in 98% of patients out
      of hospital.

PMID- 14596033
TI  - [Nutritional value of the diet in healthy pregnant women. Results of a nutrition
      survey of pregnant women].
AB  - GOAL: The purpose of the present paper is to describe the level of nutritional
      adequacy of the regular diet of pregnant women belonging to our health-care area.
      SCOPE: Health-care area of Valme Hospital, Seville. DESIGN: Randomized
      transversal descriptive study. SUBJECTS: Forty-nine pregnant women during their
      first trimester. INTERVENTIONS: The daily intake was assessed by means of a 24
      hour reminder sheet and a weekly consumption survey. The data obtained were
      compared with the recommended daily intake of nutrients and with the recommended
      daily allowances for various foods. At the same time, an anthropometric and basic
      analysis were also carried out. RESULTS: The calorie intake was as recommended
      (2,208 +/- 475 kcal/day). The diet contained excessive amounts of proteins (88 +/
      21 g/day) and fat (97 +/- 27 g/day), with a predominance of monounsaturated fats
      (46.9 +/- 5.5%) over saturated (36.6 +/- 7.2%) or polyunsaturated fats (15.1 +/-
      7%), (p < 0.0005). Nonetheless, the diet was short on carbohydrates (44%), fibre
      (18 +/- 4.9 g/day), calcium (948 +/- 353 mg/day), iron (13.4 +/- 3.1 mg/day) and
      vitamin B6 (1.1 +/- 0.8 mg/day) (p < 0.0005), and extremely short on folic acid
      (172 +/- 101 micrograms/day), (p < 0.0005). In the assessment of the diet in
      terms of daily allowances, this was sufficient in fruit (2.3 +/- 1.8/day), but
      short on dairy products (1.9 +/- 1.1/day) and extremely short on vegetables (1 +/
      0.4/day), (p < 0.0005). Only 2% of the subjects fulfilled with the recommended
      daily intake for key vitamins and minerals. The prevalence of obesity (BMI > 30
      kg/m2) was 18.4%. CONCLUSIONS: The normal diet of pregnant women in our health
      care area is short on calcium, iron, folic acid and dietary fibre, although with
      an excess of animal protein and fat.

PMID- 14596034
TI  - [Purging behaviors and nutritional status in anorexia nervosa and bulimia
      nervosa].
AB  - AIMS: The aim of the study was to investigate whether the use of purgative
      methods in patients with eating disorders (anorexia nervosa [AN] and bulimia
      nervosa [BN]) could be capable of producing changes in the nutritional status of
      the patients. SETTING AND PATIENTS: The group under study was composed of 184
      female eating disordered outpatients. One hundred and sixteen patients (63.0%)
      fulfilled the DSM-IV diagnostic criteria for BN (90 purging type, 26 nonpurging
      type). Sixty eight patients (37.0%) fulfilled the DSM-IV criteria for the
      diagnosis of AN (48 restricting type, 20 binging-purging type). METHODS: The
      assessment process included anthropometry (body circumferences and skinfold
      thickness) and body impedance analysis. RESULTS: The two subgroups of AN patients
      significantly differed from each of the BN subgroups. From a nutritional point of
      view, some significant differences between the two DSM-IV subtypes of AN existed,
      but not between the purging type and the nonpurging type of BN. CONCLUSIONS: The
      paper discusses the clinical significance of these findings. An alternative
      subtypification of AN patients is proposed: 1) restricting type [patients who
      control their food intake and do not purge]; 2) purging type [patient with true
      episodes of binging which are followed by purgative behaviors]; and 3)
      pseudopurging type [patients with subjective binging episodes who use purging
      methods].

PMID- 14596035
TI  - [Study of eating habits in a female population comparing groups with and without
      food-related diseases].
AB  - GOAL: To analyze female subjects in the rural setting to detect food-related
      disorders and factors associated with these. To isolate these factors and prevent
      the development of food-related disorders in Primary Health Care. Also to assess
      continuity in the alterations in the general, sub-clinical and bulimic
      populations. SCOPE AND SUBJECTS: 127 women with absence of dysfunctions: 57 sub
      clinical and 63 bulimics, all from south-western Spain. INTERVENTIONS: Those
      adolescents at risk of dysfunctions would present positive results in
      pathological personality traits; therefore, their identification in Primary
      Health Care would avoid the transition to complete forms and would be favour the
      theory of the continuum. RESULTS: Significant differences were found between sub
      clinical and bulimic women for mean age and age of onset of eating-related
      difficulties. Subjects without eating-related dysfunctions have a lower body mass
      index (BMI) than sub-clinical ones and the latter have less than bulimic
      subjects, both now and in the past. The objective and subjective history of
      excess weight was recorded for all three populations, together with eating
      related behaviour and the various symptoms suggesting personality disorders, and
      data on their consumption of toxic substances. CONCLUSIONS: In our sample, 30% of
      the population obtained scores above the cut-off value in the two scales used, so
      they could be considered at risk for having food-related dysfunctions and it is
      necessary to take action at the level of Primary Health Care, as it is in the
      transition from childhood to adolescence that diets are begun to be followed
      because of an excessive assessment of weight and it is in this sphere that early
      action can be taken.

PMID- 14596037
TI  - The power of words.

PMID- 14596038
TI  - Tricks for sticks.

PMID- 14596036
TI  - [Minimally invasive surgical gastrostomy].
AB  - GOAL: Description of a simple surgical gastrostomy technique fulfilling minimally
      invasive surgery criteria and presentation of the results obtained with the same,
      compared with those of other surgical gastrostomies and percutaneous techniques.
      SCOPE: Patients from various wards in the Miguel Servet Teaching Hospital in
      Zaragoza, whether admitted or out-patients, all seen by the Hospital Nutrition
      Unit and where food-restricting gastrostomy is indicated. PATIENTS AND METHODS:
      Prospective study including the first fifteen successive patients in whom a
      minimally-invasive surgical gastrostomy technique has been applied between
      January 1st, 2001, and June 30th, 2002, and in whom it was not possible, for a
      variety of reasons, to perform any kind of percutaneous gastrostomy. The
      technique was applied in the operating theatre, under local anaesthetic, using a
      Flexiflo 20 F gastrostomy probe and with antibiotic prophylaxis (Amoxicillin
      Clavulanic Acid: 2 g i.v. pre-operatively). Patients were assessed as out
      patients by the Nutrition and Surgery Unit after 10, 30 and 60 days. RESULTS: The
      procedure could be successfully completed in all cases. The mean time of the
      procedures duration was 45 minutes. In 5 patients, the procedure was performed
      without admission to hospital. The functionality of the device was 100% and it
      was effective from 10 days after the operation. Morbidity: 6.6%. Mortality after
      60 days: 0%. CONCLUSIONS: This is a procedure which is safe, simple, economic and
      capable of being performed as an out-patient procedure, thus complying with the
      criteria for minimally-invasive techniques. It is complementary or an alternative
      to percutaneous techniques in selected cases or where these are impossible, have
      failed or are contraindicated.

PMID- 14596039
TI  - Microscopic migration.

PMID- 14596040
TI  - "We do what we can." The Palestinian experience.

PMID- 14596041
TI  - EMS mythology. EMS myth #8: Public-utility models are the most efficient model
      for providing prehospital care.

PMID- 14596042
TI  - Prehospital management of pediatric SVT.
AB  - Accurate prehospital diagnosis and early initiation of emergency medical
      treatment for pediatric patients found to have supraventricular tachycardia is a
      reasonable task to accomplish and one that does not have to be anxiety-provoking.
      The most important point to remember is that the standard approach to
      resuscitation and stabilization for pediatric patients with narrow complex
      tachycardias (and those with aberrant or wide complexes identifiable as WPW)
      applies to all variations of SVT; thus, it is not necessary to precisely diagnose
      the variant prior to initiation of treatment, except for WPW, in which adenosine
      administration is contraindicated. Once the dysrhythmia is identified as SVT, the
      patient must rapidly be categorized as stable or unstable, which will then lead
      the EMS provider down the correct branch of the treatment algorithm. Every
      attempt should be made to perform a 12-lead ECG pre- and post-resuscitation, as
      well at to administer sedation prior to emergent synchronized cardioversion.
      Dosages of medications need not be memorized, provided that a readily available
      guide, such as a Broselow tape or regional tertiary care center laminated
      resuscitation card, is at hand. Finally, while termination of pediatric SVT,
      whether spontaneous or by EMS intervention, will also likely terminate the EMS
      provider's own palpitations, it is essential that these patients be seen in an
      emergency department immediately in order to accurately diagnose their medical
      condition and provide the patient and family with an appropriate disposition
      based on the events surrounding the incident.

PMID- 14596043
TI  - Questioning your treatment of tachycardia.
AB  - These six questions may make it easier to guide your steps as critical minutes
      pass while treating your tachycardic patient. Ultimately, local protocols and the
      contents of your drug box may limit some of your choices, but good decisions can
      start the process. Adequate oxygenation, establishing IV lines and diagnosing
      specific rhythms are the first steps toward successful treatment of your next
      patient.

PMID- 14596044
TI  - The spectrum of cardiovascular disease.

PMID- 14596045
TI  - Regular wide-complex tachycardia recognition.

PMID- 14596046
TI  - Innovations in pulse oximetry.

PMID- 14596047
TI  - Improving helicopter response.

PMID- 14596048
TI  - Safety in EMS: a general perspective.

PMID- 14596049
TI  - Front-line leadership. Chapter 3: discovering secrets.

PMID- 14596050
TI  - Meshing missions.
AB  - Hospitals and Federally Qualified Health Centers (FQHCs) have a lot to offer each
      other. From diverting non-emergency ED visits to allowing hospitals to divest
      themselves of unprofitable primary care services, it is a partnership worth
      exploring.

PMID- 14596051
TI  - 2003 AHA environmental assessment.

PMID- 14596052
TI  - Connecting the dots.
AB  - A top priority for patients, physicians and staff at Evergreen Hospital Medical
      Center in Kirkland, Wash., was upgrading their public hospital's information
      technology system. The result: a system that links all hospital functions,
      caregivers and staff.

PMID- 14596053
TI  - Caution: attorneys general are watching your M&A activities.
AB  - State AGs have been paying close attention to not-for-profit health care mergers
      and acquisitions. This article gives you advice on how to protect your
      organization from a lawsuit.

PMID- 14596054
TI  - Is the EMR dead?

PMID- 14596055
TI  - Technology. Most wired 2003.

PMID- 14596056
TI  - Case management and compliance: what every CM needs to know.

PMID- 14596057
TI  - Include case managers in hospital's disaster plan.

PMID- 14596058
TI  - Do patients get uniform case management?

PMID- 14596059
TI  - Checkoffs play key role in SICU improvement.

PMID- 14596060
TI  - Proper patient ID focus of hospital initiative.

PMID- 14596061
TI  - CMS hopes final EMTALA rule will ease burden.

PMID- 14596062
TI  - 'Just the facts' not enough if patient asks about bill.

PMID- 14596063
TI  - How do your salary and benefits stack up against your case management peers'?

PMID- 14596064
TI  - Creativity helps with CM recruitment, retention.

PMID- 14596065
TI  - Global health issues.

PMID- 14596066
TI  - Painful nipples in nursing mothers.

PMID- 14596067
TI  - Lateral elbow pain.

PMID- 14596068
TI  - Healthy scepticism.

PMID- 14596069
TI  - SARS: a new infectious disease for a new century.
AB  - BACKGROUND: A new infectious disease swept the world in early 2003, causing
      restrictions on international travel and economic downturn in affected countries.
      OBJECTIVE: This article aims to provide an overview of the epidemic of severe
      acute respiratory syndrome (SARS). DISCUSSION: SARS is caused by a new
      coronavirus thought to be of animal origin. The virus induces symptoms of
      atypical pneumonia, clinically indistinguishable from similar syndromes. The
      severity is such that a 15% mortality rate has been reported. No treatment has
      yet been identified as reliably successful. Transmission is by droplet spread,
      requiring close contact. Stringent infection control precautions in health care
      institutions, broad isolation measures in affected communities and international
      surveillance with barrier restrictions to travel have led to termination of the
      epidemic. As of July 11, 2003, 8437 people in 32 countries have been affected,
      with 813 deaths reported.

PMID- 14596070
TI  - Infectious mononucleosis.
AB  - BACKGROUND: Infectious mononucleosis is caused by the ubiquitous Epstein-Barr
      virus. It is a common condition usually affecting adolescents and young adults.
      Most cases are mild to moderate in severity with full recovery taking place over
      several weeks. More severe cases and unusual complications occasionally occur.
      OBJECTIVE: After presenting a case of severe infectious mononucleosis, the
      spectrum of disease is given. Diagnosis and complications are reviewed as well as
      management including the possible role for antiviral medications or
      corticosteroid therapy. DISCUSSION: The majority of cases of infectious
      mononucleosis are self limiting and require only supportive care. More severe
      cases, although unusual, may require admission to hospital and even to an
      intensive care unit. Corticosteroid therapy may be indicated for severe airway
      obstruction or other severe complications, but should be avoided unless the
      benefits outweigh potential risks. Antiviral therapy has no proven benefit.

PMID- 14596071
TI  - Cytomegalovirus. A common virus causing serious disease.
AB  - BACKGROUND: Human cytomegalovirus (CMV) is a herpes virus that causes severe
      illness and death in people whose immune systems are compromised, including organ
      and bone marrow transplant recipients, HIV infected people, those on
      immunosuppressive drugs and newborns infected during pregnancy. OBJECTIVE: This
      article aims to present a clear guide to diagnosis and treatment of CMV in at
      risk patients in the community. DISCUSSION: Cytomegalovirus is a common infection
      in the community, but diagnosis is often seen as difficult. The use of careful
      clinical assessment tests and a clear diagnostic algorithm can provide
      appropriate diagnosis in most immunocompromised patients, pregnant women and
      newborns with CMV. Treatment strategies and available antivirals are improving,
      complementing the advances made with diagnostic techniques and algorithms.

PMID- 14596072
TI  - Hepatitis C and general practice: the challenge continues.

PMID- 14596073
TI  - Epidemiology of hepatitis C virus infection in Australia.

PMID- 14596074
TI  - Preventing transmission of hepatitis C.

PMID- 14596075
TI  - Acute hepatitis C.

PMID- 14596076
TI  - Chronic hepatitis C.

PMID- 14596077
TI  - Pretest counselling and diagnosis.

PMID- 14596078
TI  - Post-test counselling and initial management.

PMID- 14596079
TI  - Ongoing management of hepatitis C.

PMID- 14596080
TI  - Antiviral therapy for chronic hepatitis C.

PMID- 14596081
TI  - Structured problem solving in general practice. 3.

PMID- 14596083
TI  - Flashes and floaters. Eye series--9.

PMID- 14596082
TI  - Introduction to monitoring. What is what you prescribed actually doing?
AB  - BACKGROUND: Having written a prescription for the patient, it is important to
      monitor for the effects of the drug. OBJECTIVE: This article discusses the
      importance of patient monitoring as part of the prescribing process, and in
      particular, what factors to monitor. DISCUSSION: Monitoring of drug therapy is an
      important part of the prescribing process in enhancing the drug's effectiveness.
      This is partly due to the large variability in patient response to any given dose
      of a drug. The drug's effect as well as adverse effects should be actively
      sought, and dosage alterations made in order to enhance the drug's effect. In
      some cases, this involves directly monitoring for the drug's effects, and in
      other cases using surrogate markers.

PMID- 14596084
TI  - Prison health. A different place for GPs.
AB  - BACKGROUND: Imprisonment rates in Australia have been steadily increasing over
      the past decade. Prisoners have high rates of substance use and dependence,
      mental illness, self harming behaviours and infectious disease. OBJECTIVE: This
      article discusses health issues of prisoners and the role of general
      practitioners in prison health. DISCUSSION: The standard of health care provided
      for prisoners should be equivalent to that available in the general community.
      Medical officers working within prisons need to be competent GPs with particular
      skills in managing the unique patterns of morbidity encountered. In addition,
      public health advocacy, an ability to examine the frequent ethical issues at
      stake, and close links with colleagues both within prisons and in the community
      are needed.

PMID- 14596085
TI  - GPs' views of quality initiatives to improve stroke outcomes following carotid
      endarterectomy.
AB  - BACKGROUND: General practitioners' satisfaction with previous referral of
      patients may influence their future specialist referral patterns. METHOD: A
      postal survey of 123 GPs assessing satisfaction with discharge planning and
      communication from operating surgeons for patients following carotid
      endarterectomy. General practitioners' views of quality indicators for patient
      referral also were assessed. RESULTS: General practitioners were significantly
      more likely to be 'very satisfied' with the level of communication from the
      operating surgeon (83%) than the discharge planning (65%), (p < 0.001). The most
      highly ranked quality indicator for use in referring a patient for carotid
      endarterectomy was the 30 day postoperative complication rate per surgeon (n =
      69, 56% 'very useful'). Over one-third (35%) remembered seeing the relevant
      guidelines for GPs. DISCUSSION: General practitioners value information about
      surgeon performance when making referral decisions. They are less satisfied with
      discharge planning than other aspects of care.

PMID- 14596086
TI  - The family GP. A valued resource for families with young babies.
AB  - BACKGROUND: There is little research citing the changing health needs of families
      with newborn babies. METHODS: Sixteen families participated in a series of
      interviews during their babies' first year. Data collection and analysis were
      driven by grounded theory techniques. RESULTS: Parents drew upon a range of
      resources and strategies to maintain both individual and family health. Child and
      family oriented general practitioners were an important health resource, and
      parents spent considerable effort in finding a suitable one. DISCUSSION: General
      practitioners seen as trustworthy, accessible and skilled are highly valued and
      sought after.

PMID- 14596087
TI  - Misplaced fear.

PMID- 14596088
TI  - Marion's message. The necessary cesarean.

PMID- 14596089
TI  - What do you do to overcome your fears in midwifery and/or birth?

PMID- 14596090
TI  - Courage.

PMID- 14596091
TI  - Fear, society and birth.

PMID- 14596092
TI  - Sharing the stories.

PMID- 14596093
TI  - Fearful fantasies.

PMID- 14596094
TI  - Connecting to birth.

PMID- 14596095
TI  - Fear of death during labour.
AB  - The expression of fear of death during labour is common when the physiological
      processes are obviously efficient and when the perinatal period is considered, in
      retrospect, to have been a positive experience. We propose two kinds of
      interpretation: (1) One is not specifically human. A physiological fear is the
      expression of a rush of adrenaline just before the "fetus ejection reflex." The
      paradoxical oxytocic effect of adrenaline was demonstrated several decades ago.
      (2) One is specifically human. It takes into account our knowledge of death and
      the reduction of neocortical control during labour.

PMID- 14596096
TI  - Though I walk through the valley....

PMID- 14596097
TI  - The role of fear in the U.S. birthing process.

PMID- 14596098
TI  - The department.

PMID- 14596099
TI  - Cruelty in the maternity wards revisited.

PMID- 14596100
TI  - Cytotec induction and off-label use.

PMID- 14596101
TI  - A question of words.
AB  - By tracing powerful patriarchal words originally applied to mass production,
      military manoeuvres, building construction and war, and then ascribing them to
      birth we can see how Western culture denounces the mother's true role as the
      central and essential figure in the birth of her own children. Many words for
      birth imply fear, doubt and opposition. Yet when we consciously select words to
      describe giving birth as a form of art--a giving of creation--we can not only
      place the woman at the centre of the birth event, but also grant the respect and
      honour due her as she brings forth new life.

PMID- 14596102
TI  - Lotus birth: a ritual for our times.

PMID- 14596103
TI  - The birth of Empower! Newsletter.

PMID- 14596104
TI  - Preventing complications with nutrition.

PMID- 14596105
TI  - Lessons learned from a great chef.

PMID- 14596106
TI  - India ink: homeopathic sepia.

PMID- 14596107
TI  - Interviews with maiden midwives reaching out to the next generation. Interview by
      Mary Kroeger.

PMID- 14596108
TI  - Meet Kiyoko Inoue, Japanese midwife.

PMID- 14596109
TI  - Working relations: midwives and obstetricians in The Netherlands.

PMID- 14596110
TI  - A time to be born.

PMID- 14596111
TI  - Norway: the breastfeeding top of the world.

PMID- 14596113
TI  - What constitutes nursing research?

PMID- 14596112
TI  - A home away from home birth.

PMID- 14596114
TI  - Paternalism in nursing and healthcare: central issues and their relation to
      theory.
AB  - Paternalistic practices, wherein providers confer a treatment or service upon a
      person or persons without their consent, ostensibly by reason of their limited
      autonomy or diminished capacity, are widespread in healthcare and in societies
      around the world. In the United States, paternalism in health and human services
      is widespread and probably increasing with newly emergent forms. Numerous issues
      surround paternalistic practices. In this column, the author examines these
      issues in relation to theory development in healthcare and nursing as well as
      theory as a guide to practice. It is suggested that scientific and ethical
      knowing are not separate but must be united in theoretical structures that
      include both in unity, along with an appreciation of the infinite complexity of
      life as it is humanly lived. It is also suggested that nursing's unique theory
      base of frameworks that honor human dignity and focus on human experience offers
      an opportunity for leadership in further developing theoretical frameworks that
      transcend paternalistic practices.

PMID- 14596115
TI  - Developing a nursing perspective on spirituality and healing: questions and
      answers following a letter to the editor.

PMID- 14596116
TI  - The American Nurses Association Code of Ethics: a reflection on the ethics of
      respect and human dignity with nurse as expert.
AB  - The American Nurses Association Code of Ethics for Nurses calls for the nurse to
      practice with compassion and respect for every individual. What are the ethics
      and challenges of practicing professional nursing with expertise and educating a
      new generation of nurses while incorporating the interpretive statements into
      practice? This column differentiates the traditional biomedical views on human
      dignity and respect while exploring the embedded ethics of respect and self
      determination and what it truly means to be an expert of nursing from the
      theoretical perspective of the human becoming school of thought.

PMID- 14596117
TI  - Understanding the stranger.
AB  - This column presents teaching-learning processes involved in gaining an
      understanding of the stranger or the other--the one we see as so different from
      ourselves. A paradox concerning the stranger or the other exists in this 21st
      century. Never has the world been more dangerous, with terrorism continuing to
      spark suspicions of those that are different from us. And, never, at the same
      time, has the world been more in need of finding ways to embrace those that are
      different and those that are viewed as the stranger to the larger society. The
      concept of hospitality and the concept of true presence are explored, in light of
      human differences, as possibilities for engaging the stranger.

PMID- 14596118
TI  - Abstractions and particulars: learning theory for practice.
AB  - Debates continue about the role of nursing theory in nursing and yet it is
      generally accepted that all knowledge is theoretical and all learning requires
      abstract theory. This column looks at the interplay between abstract theoretical
      concepts and particulars from nursing practice and research that are informed by
      theory and that at the same time expand understanding of the abstract notion.
      Examples from practice and research highlight the critical role of nursing
      theory.

PMID- 14596119
TI  - Conceptual models of nursing: international in scope and substance? The case of
      the Roy adaptation model.
AB  - This column focuses on exploration of the international applicability of
      conceptual models of nursing developed by nurse theorists from the United States.
      Viewpoints put forward by Marilyn E. Parker and William K. Cody are presented.
      Then, nurse scholars from Colombia and Japan discuss their experiences with use
      of the Roy adaptation model in their countries.

PMID- 14596120
TI  - The lived experience of feeling very tired: a study using the Parse research
      method.
AB  - The purpose of this study was to answer the research question, What is the
      structure of the lived experience of feeling very tired? The Parse research
      method was used to discover the meaning of feeling very tired for 10 women
      volunteer participants. The major finding of the study is the structure: The
      lived experience of feeling very tired is devitalizing languor arising with
      engaging endeavors amid pulsating moments of repose-revive. The study finding
      contributes knowledge about feeling very tired and its connection to health and
      quality of life. The structure is discussed in light of the principles of human
      becoming, and suggestions are made for future research.

PMID- 14596121
TI  - The lived experience of feeling very tired: a study of adolescent girls.
AB  - This Parse method phenomenological-hermeneutic study centered on the phenomenon
      of feeling very tired. It was part of a multisite study on feeling very tired
      using the human becoming theory and the Parse research method. The purpose of the
      study was to explore the meaning of feeling very tired as described by a group of
      high school girls. The finding, which is the structure of the lived experience of
      feeling very tired, surfaced from the dialogues: Feeling very tired is struggling
      with being attentively present as calming contentment emerges amid discomforting
      discordance. The conclusion of the study is that feeling very tired is a complex
      paradoxical rhythm.

PMID- 14596122
TI  - Community dwellers' perspectives on the experience of feeling very tired.
AB  - Feeling very tired is a phenomenon experienced by all humans at some point in
      their life. As a means of more fully understanding the human experience of
      feeling very tired, this concept was explored with a group of 10 community
      dwelling individuals who had no expressed health concerns. The Parse research
      method was used to answer the research question, What is the structure of the
      lived experience of feeling very tired? The central finding of this study is the
      structure: The lived experience of feeling very tired is dissipated vigor arising
      with monotonous disquietude amid spirited cherished engagements. The structure
      was conceptually integrated with the human becoming theory as: feeling very tired
      is powering the languaging of valuing connecting-separating. The findings are
      discussed in relation to human becoming and future research.

PMID- 14596125
TI  - The relationship of nursing theory to practice and research within the British
      context: identifying a way forward.
AB  - In this column, the author presents the current relationship of nursing theory to
      practice and research within the British context and suggests a way forward as
      suggested by Nightingale in order to guide future development.

PMID- 14596123
TI  - Comparison of three Parse method studies on feeling very tired.
AB  - This article compares three human becoming studies on feeling very tired. The
      studies were conducted by Dr. Rosemarie Rizzo Parse, Dr. Mary H. Huch and Dr.
      Debra A. Bournes, and Dr. Steven Baumann. The comparison is conducted through the
      lens of the following questions: What have we learned about feeling very tired
      from these studies? What are similarities in the three studies? What are
      differences in the three studies? And, what new questions can be posed concerning
      feeling very tired? Unique knowledge for nursing is explicated on feeling very
      tired as a universal lived experience of health.

PMID- 14596126
TI  - Theory and practice: A conversation with Marilyn E. Parker.

PMID- 14596127
TI  - Giving credit where it is due.

PMID- 14596128
TI  - [Academic success of students in nursing colleges. Part I: Factors contributing
      to academic success].

PMID- 14596130
TI  - Essential managerial attributes of the nowadays nursing service manager in the
      South African context.
AB  - Nursing service managers need certain essential managerial attributes in taking
      the lead in effective management of the nowadays health care organisations in
      South Africa. Major changes in restructuring and human resources planning are
      taking place through transformation of health services and specific managerial
      attributes are needed in this scenario. Without nursing service managers with the
      necessary managerial attributes, change in the health care environment will be
      hampered and planning, organising, directing and control of the delivering of
      quality care will be negatively influenced. The research problem was addressed in
      the following question that guided the study: Which essential
      attributes/characteristics should a nursing service manager possess to run a
      health care service effectively? It was unclear what the opinions of all level of
      nurse managers were regarding the necessary managerial attributes the health
      services manager currently need to run the current health care services
      effectively. This study aimed at highlighting the necessary attributes of the
      nowadays nursing service manager in running a health care institution in the
      current health care environment of South Africa. Purposive sampling was done and
      forty-five functional, middle and top-level managers registered for a second year
      degree course in Health Services Management at a South African university
      participated in the study. The findings indicated important managerial and
      leadership attributes, which the current nursing service manager should possess.
      This article will only discuss the important managerial attributes needed. A
      conceptual framework came to the fore according to which an example of a self
      evaluation instrument was compiled for nursing service managers for future use.
      The results of the data analysis indicated that the nursing service manager
      should promote good interpersonal relationships with colleagues, subordinates and
      patients through the attributes of openness, being inviting and empowering
      behavior. The purpose of this article is to make nursing service managers more
      aware of the necessary attributes they should possess and should develop to
      manage nursing services more effectively.

PMID- 14596129
TI  - Exploring the fear of contracting HIV/AIDS among trauma nurses in the province of
      Kwazulu-Natal.
AB  - A qualitative study, using phenomenology as an approach was conducted. The title
      of the study was "Exploring the fear of contracting HIV/AIDS among trauma nurses
      in the province of Kwazulu-Natal". Participants were selected on the basis of
      category (registered nurses), workplace (level one trauma units), and work
      experience (six months experience in a trauma unit). Twelve nurses participated
      in the study, six from the state institutions and six from the private
      institutions. The objectives of the study were to explore the fear of contracting
      HIV/AIDS, its effect on their personal/working lives and how they coped with it.
      The findings of the study revealed that trauma nurses perceived themselves to be
      at risk of acquiring HIV/AIDS from their working environment despite the
      available precautionary measures. Needlestick injuries appeared to be the main
      source of fear. They used different coping and defence mechanisms effectively to
      cope with this fear of contracting HIV and none were in any emotional crisis.
      Education at different levels and development of support networks has been
      recommended as the key strategies to decrease these fears. Other recommendations
      include improving the quality and availability of protective materials and
      equipment, making HIV/AIDS a notifiable disease as well as improving general and
      specific beliefs that increase coping.

PMID- 14596131
TI  - Accompaniment needs of first year nursing students in the clinical learning
      environment.
AB  - The clinical learning environment creates many opportunitics for student learning
      and the development of critical competencies in the nursing profession. The
      learning that takes place in this environment, however, confronts the first year
      nursing student with challenges that are absent from the classroom situation and
      causes the student to experience a significant amount of uncertainty and anxiety.
      The study revealed that the students experience uncertainty due to the lack of
      opportunities to develop competence in providing nursing care. The contributing
      factors towards this experience are: unavailability and inaccessibility of staff
      due to time constraints; shortage and/or absence of equipment to fulfil nursing
      duties and meet the needs of patients; conflict in the expectations of nursing
      school personnel and clinical nursing personnel in hospitals, as well as a lack
      of awareness among senior professionals of the needs and problems of first year
      nursing students in the clinical health care environment. Furthermore the
      students experienced the nature of the clinical learning programme as disrupting
      the continuity in patient care learning experiences, and the guidance and support
      by nursing personnel in the clinical learning environment as inadequate. The aim
      of this study was to reflect the importance of effective accompaniment by
      tutors/mentors, personnel in the clinical environment and any other person
      involved in the education of the first year nursing student, to prepare and
      enable him/her to become a knowledgeable, safe, competent nursing practitioner.

PMID- 14596132
TI  - When ideal and real culture clash--trust, infidelity and condom use.
AB  - With high rates of HIV transmission in South Africa, the correct and consistent
      use of condoms has become critically important. The findings reported in this
      article form part of a larger study that investigated the vulnerability of women
      to HIV infection. This article concentrates on one dimension of the study: how a
      clash between real and ideal culture negatively impacts upon condom use. This
      study, conducted in Bloemfontein, revealed that an ideal culture of trust,
      resulted in non condom use. On the other hand, this study also revealed that
      despite the emphasis on an ideal culture of trust, a real culture of infidelity
      exists. This places individuals at risk of contracting HIV, as condom use is
      guided by ideal rather than real culture.

PMID- 14596133
TI  - Treatment utilisation and trauma characteristics of child and adolescent
      inpatients with posttraumatic stress disorder.
AB  - OBJECTIVE: Few empirical studies have addressed the impact of trauma exposure and
      posttraumatic stress disorder (PTSD) on treatment utilisation and outcome in
      South African youth. This study was undertaken to document demographic, clinical,
      and treatment characteristics of child and adolescent inpatients with PTSD.
      DESIGN: A retrospective chart study of all patients presenting to a child and
      adolescent inpatient unit was conducted between 1994-1996. For children and
      adolescents diagnosed with PTSD; demographic, diagnostic and treatment variables,
      including trauma type, family history, and delays in treatment seeking, were
      documented. SETTING: Child and Adolescent Psychiatric Inpatient Unit, Tygerberg
      Hospital, Cape Town. SUBJECTS: Children and adolescents (2 to 18 years)
      presenting to an inpatient unit (n = 737). RESULTS: 10.3% (n = 76) met diagnostic
      criteria for PTSD. Gender differences were clearly evident: PTSD was six times
      more prevalent in girls (65 with PTSD were female and 11 were male); girls were
      most likely to have experienced rape or sexual abuse while boys were most likely
      to have witnessed a killing. Psychotherapy was the most common intervention for
      PTSD, followed by treatment with a tricyclic antidepressant. 97.4% of children
      and adolescents who were treated were improved at treatment endpoint. Delays in
      seeking treatment and problems with the primary support group were highly
      prevalent. CONCLUSION: PTSD is a common disorder that is responsive to treatment
      with psychotherapy and/or tricyclic antidepressants in child and adolescent
      inpatients. These findings underscore the importance of early identification and
      treatment of childhood PTSD in mental health settings, in particular tertiary
      service institutions.

PMID- 14596134
TI  - Journaling: a quasi-experimental study of student nurses' reflective learning
      ability.
AB  - The use of journaling or journal writing in clinical education is one of the
      strategies used to develop critical thinking. Reflective journal writing, as it
      is commonly known, can nurture many qualities of a critical thinker and promote
      thoughtful nursing practice. Using a quasi-experimental design in this study,
      reflective journaling was introduced to a sample of first year Bridging Course
      student nurses at a Private Nursing Education Institution, to assess its
      effectiveness in reflective learning. The study design enabled comparisons
      between two groups: one group of students assigned to do journaling (experimental
      group) and another group of students (control group) who did not journal. The
      students in the experimental group were given a period of eight weeks to journal
      their clinical experiences. At the end of this period, both groups were given an
      exercise, based on a clinical situation, to analyse reflectively and a comparison
      made on their performance. Descriptive statistics were used to analyse data and
      Fisher's Exact Test was used to determine the significance of differences
      observed within and between groups. The results showed that students in the
      experimental group performed better in exploring alternatives of action (p <
      0.10) and formulating responses in similar future situations (p < 0.05) during
      the process of reflection. There was no significant difference between the
      groups' scores with regard to their ability to describe the clinical experience,
      to explore their related feelings, to evaluate the experience and to
      interpret/create meaning for themselves. Recommendations are made for continued
      student support and guidance during clinical education if reflection is
      considered to enhance reflective, thoughtful nursing practice.

PMID- 14596135
TI  - Witnessed resuscitation--exploring the attitudes and practices of the emergency
      staff working in level I emergency departments in the province of KwaZulu-Natal.
AB  - AIM: The aim of this study was to explore the attitudes and practices of
      witnessed resuscitation by the staff working in Level I Emergency Departments in
      the province of KwaZulu-Natal. Witnessed resuscitation involves the 'medical'
      resuscitation of the patient with their relatives or loved ones present in the
      resuscitation room (Boyd, 2000:171). METHODOLOGY: A qualitative approach was used
      to explore the participants' attitudes and practices of witnessed resuscitation
      using individual semi--structured interviews. The principle of theoretical
      saturation was applied and a total of six participants from two Level I Emergency
      Departments (one provincial and one private institution) were included in this
      study. FINDINGS: The emergency staff disliked the idea of witnessed
      resuscitation. They believed it to be a harmful experience for the witnesses, a
      threat to the resuscitation process and the emergency staff, and impossible to
      implement in their Emergency Departments. There were however, subtle references
      made during the interviews that revealed some aspects of witnessed resuscitation
      that the staff favoured once they had considered the practice. There were no
      written policies to dictate how the relatives were handled, but all the staff
      agreed that the relatives were asked to wait outside the resuscitation area, were
      kept informed and then brought in when the patient was stable or had died. A
      number of recommendations are suggested in an attempt to introduce witnessed
      resuscitation as an option in KwaZulu-Natal's Emergency Departments.

PMID- 14596136
TI  - The clinic supervisory system as experienced by nurse supervisors.
AB  - A lack of proper monitoring and supervision of clinics in the King William's Town
      Health District (Eastern Cape) was highlighted by members of the public in the
      local newspaper, The Daily Dispatch, during 1999. A clinic audit conducted by the
      Health Information Unit of the King William's Town Health District further
      revealed the inadequacies of clinic supervision in this district. This article
      describes the qualitative study that was conducted with the aim of optimising
      clinic supervision in this health district. The study brought to light two issues
      that appear to be paramount in ensuring optimal clinic supervision. These are:
      The importance of formal and informal preparation of clinic supervisors for the
      supervisory role The support system that the clinic supervisors require to
      perform their duties effectively. The focus of this article will be on the
      discussion of the research findings as well as guidelines that were developed to
      optimise clinic supervision.

PMID- 14596137
TI  - Care of the pediatric patient with uveitis.
AB  - This article focuses on the care of the pediatric patient with uveitis. It
      discusses the impact, major causes, types, treatment, nursing care, and follow up
      necessary to best manage this complex and multifaceted disease.

PMID- 14596138
TI  - Retinoblastoma: care and support of the pediatric patient and family.
AB  - This paper presents the holistic approach to the care of the pediatric patient
      with strabismus. It discusses preoperative management, contemporary surgical
      procedures including postoperative suture adjustments, complications and the care
      and management of the patient and family on the pediatric unit. It reviews
      discharge instructions including pain management, postoperative safety and the
      follow-up appointment with the surgeon. Methods of determining the level of
      knowledge of the child's primary caregiver are also a major focus.

PMID- 14596139
TI  - A study of supervised practice from the perspective of the supervisor and the
      supervised.
AB  - This is the ASORN Edna Ashy Award Winning Project for 2002. Ms. Stringer has a
      long and varied career in ophthalmic nursing, working both as a clinical
      specialist and an educator. Currently she functions as an educator and nurse
      practitioner for the University of Sheffield. She performs clinical duties in the
      ophthalmic casualty department and teaches the remainder of the week. Her
      academic interest include, the development of ophthalmic nursing practice as a
      specialty, practice supervision models and applying research-based data to daily
      practice patterns. Her qualifications include, Ophthalmic Nursing Diploma (OND),
      Registered Nurse (RN), BA)hons, and MA(ed), Masters in Education.

PMID- 14596140
TI  - Visual assessment of the pediatric patient.

PMID- 14596141
TI  - Effect of culture media temperature on bacterial recovery from corneal scrapings.

PMID- 14596143
TI  - ASNA independent study activity--cultural assessment of Koreans.

PMID- 14596144
TI  - It starts with you. It's up to nurses to act now to strength the RN workforce and
      help create a better future for the profession.

PMID- 14596148
TI  - Fulmer SPICES: an overall assessment tool of older adults.

PMID- 14596145
TI  - Protecting the privacy of patients' health information.

PMID- 14596151
TI  - Extraoral x-ray film continues to evolve, improve.

PMID- 14596150
TI  - Specialized dentistry.
AB  - Knowledge of the disciplines of dentistry is needed for the dental assistant to
      properly communicate with the patient, insurance companies, labs and medical
      offices. It also helps the dental assistant identify workplace settings. It is
      the responsibility of the dental assistant to become familiar with these subject
      areas in order to better communicate with patients about their treatment. While
      it is nearly impossible to know the details of all of the thousands of dental
      procedures performed on patients, knowledge of the common topic areas helps the
      dental assistant to provide additional information to the patient.

PMID- 14596152
TI  - Success for nursing in the 78th legislative session.

PMID- 14596153
TI  - Hospitals survive stormy legislative session.

PMID- 14596154
TI  - A multi-dimensional orthodontic and prosthodontic study cast analysis.

PMID- 14596155
TI  - The significance of cranial factors in diagnosis and treatment with the advanced
      lightwire functional appliance.
AB  - These two cases have been chosen to illustrate the very considerable potential
      for change once the cranial lesions have been identified and their correction is
      planned as part of  treatment.

PMID- 14596156
TI  - The Tip-Edge appliance--a combination of Begg and Straight Wire treatment.

PMID- 14596157
TI  - Expansion by the straightwire appliance.

PMID- 14596158
TI  - Some thoughts about research.

PMID- 14596159
TI  - Fluoride case goes to Washington's Supreme Court.

PMID- 14596160
TI  - Baby boomers making use of health care services.

PMID- 14596161
TI  - Concentration levels of fluoride in bottled drinking water.
AB  - PURPOSE: The purpose of this study was to classify brands of bottled water by
      manufacturer assigned labeling to verify the concentration of fluoride for those
      brands that claim to contain fluoride, and to determine the existence and
      concentration of fluoride for those brands that do not cite fluoride or list it
      as undetermined on the product label. METHODS: A convenience sample of bottled
      drinking waters (N = 65) sold throughout the state of West Virginia was obtained
      for this study. Among the 65 brands, six different types of water were identified
      based on common wording displayed on the package. A sample (150 mL) was taken
      from each brand of water. Each sample was analyzed using an Orion EA940
      microprocessor which calculates the fluoride concentration of a given sample. All
      analyses of bottled waters were reported using an inorganic chemistry laboratory
      report. RESULTS: Results, reported in frequencies and percentages, indicate that
      only 12.3% (N = 8) of the brands tested contained an optimal level of fluoride
      (0.6 to 1.2 parts per million); 95% of the bottled water analyzed did not list
      fluoride; 1.1% (N = 7) of the bottled waters analyzed were obtained from
      municipal sources; and of the sixty-five brands tested, only three brands
      contained a fluoride concentration consistent with that listed on the label or as
      identified by the manufacturer. CONCLUSIONS: Several main points can be
      summarized: 1) solely drinking bottled water may not provide sufficient fluoride
      to maintain optimal dental health; 2) most bottled waters contain low
      concentrations of fluoride and therefore, in and of themselves are not a risk for
      fluorosis; and 3) bottled waters are named and packaged in a variety of ways;
      however, their composition is virtually the same.

PMID- 14596162
TI  - Survey for teaching patient education in the dental hygiene curriculum.
AB  - PURPOSE: The primary objective of this descriptive study was to assess if and
      when dental hygiene curricula provide practice opportunities to students in
      teaching patient/client oral health self-care techniques and whether that
      experience was prior to their first clinical experience. METHODS: Data were
      collected through the use of descriptive research utilizing a two-page
      questionnaire containing some open-ended items. The survey was mailed to all 255
      accredited dental hygiene programs in the United States and Puerto Rico in August
      2000; 174 were returned. There was no pilot testing. The primary mailing resulted
      in a 68.2% return rate so a second mailing was not deemed necessary. Program
      administrators were asked to fill in their responses or pass the survey to
      faculty members in the program who teach preventive dentistry. The participating
      respondents were asked to describe the preventive dentistry portion of their
      curriculum by checking lists in the questionnaire and/or by writing responses in
      space provided. Specifically, respondents were asked to indicate how their
      program evaluated students on teaching patients self-care techniques in a
      preclinical and clinical setting. RESULTS: Based on this survey, almost half of
      all dental hygiene programs provide a preventive dentistry course. The other half
      incorporates the appropriate information in a preclinical course. Approximately
      80% of all programs responding offer a unit in their curriculum that focuses on
      patient education, and almost 80% evaluate students' patient education technique
      before they begin working in a clinical setting. The results of the survey
      revealed that nearly all programs view patient education as highly important and
      would strongly agree that patients should be able to demonstrate mastery of their
      newly learned techniques. CONCLUSION: The results indicate that competency in
      student's teaching patient/client oral health self-care techniques is a priority
      for dental hygiene programs.

PMID- 14596163
TI  - A pilot study of hand and arm musculoskeletal disorders in dental hygiene
      students.
AB  - PURPOSE: This study was designed to determine the relationship between
      musculoskeletal disorder symptoms and vibration in dental hygiene students as a
      pilot for a larger scale study. METHODS: A custom-designed questionnaire was
      distributed to three intact student groups: those accepted for admission, those
      at the end of the first year, and graduating students at the end of the second
      year. Data were analyzed using tabular and multivariate analysis. Students
      increased their use of ultrasonic instruments from 0.2 to 2.8 to 7.3 hours per
      week over the three years. Dental hygiene students with symptoms of numbness in
      the upper extremities used ultrasonic scalers a mean of 8.2 hours per week
      compared to 2.8 hours of use by students with no upper extremity numbness. These
      students also used manual instruments 10.1 hours and 4.8 hours per week,
      respectively. RESULTS: Logistic regression revealed a significant association
      between hours of use of ultrasonics and upper extremity numbness/tingling, with
      an odds ratio of 1.10 for each increased hour of use (95% CI 1.01-1.19; chi
      square = 4.9). A similar result was found for manual instrument use. CONCLUSION:
      Results indicate that musculoskeletal disorder symptoms may increase with the use
      of ultrasonic and/or manual instruments.

PMID- 14596164
TI  - The retrocuspid papillae: a clinical evaluation of 51 cases.
AB  - PURPOSE: This study was undertaken to increase the knowledge of dental hygienists
      and dentists of a normal anatomic gingival structure, the retrocuspid papillae
      (RCP), so that patients can avoid clinical misinterpretation and unnecessary
      biopsies. METHODS: In a three-part study, dental hygienists were surveyed on
      their knowledge of the RCP via questionnaire. Oral examinations of adult patients
      in a dental hygiene clinic were performed to obtain data on the RCP, and detailed
      clinical information from the pathology reports of surgically removed RCPs were
      tabulated. These findings were compared with findings from previously reported
      cases. RESULTS: Part one: of the dental hygienists surveyed, 2.8% knew about the
      RCP. Part two: of 232 adults examined, 9.1% had RCP. The age range was 20 to 63
      years; 57% of the RCPs were unilateral, and 43% were bilateral. Part three: the
      RCP represented 16.2% of the biopsied fibrous lesions of the mandible over a 12
      year period. Their histologic features contributed to their clinical morphology
      of a mound or sessile nodule with or without a papillary surface. CONCLUSIONS:
      The RCP is more prevalent in children and females and in a bilateral gingival
      distribution. It is a normal anatomic structure that regresses with age and
      requires no treatment.

PMID- 14596165
TI  - A public aid clinic prototype: utilizing a dental hygiene educational facility to
      increase access to care.
AB  - Few dentists in a rural Midwestern community participate in providing oral health
      care to public aid recipients. In response, faculty at a baccalaureate degree
      dental hygiene program located at Southern illinois University, Carbondale (SIUC)
      proposed, developed, and implemented the Heartland Dental Clinic to serve
      Medicaid participants. The unique program utilizes existing facilities, staff,
      and students to provide comprehensive oral health care to underserved
      populations. The state awarded a small grant to cover start-up costs. Two dental
      units were upgraded with fiber optics to allow restorative procedures. Dental
      hygiene students provide intake examinations and preventive care, while a staff
      dentist provides restorative care, dentures, and examinations. Dental technology
      students and faculty fabricate prostheses. A part-time clinic manager facilitates
      communication, patient scheduling, and billing. Two local Rotary Club members
      volunteer as receptionists for the clinic on the one evening per week that the
      clinic operates. The Rotary Club purchased educational pamphlets, a
      television/VCR, videotapes, and two signs for the clinic. By locating the clinic
      in the existing SIUC facility and utilizing dental hygiene students, a staff
      dentist, volunteer receptionists and dentists, student workers, and health care
      management interns, the clinic overhead costs have been kept to a minimum. The
      clinic provides a unique opportunity for dental hygiene students to experience
      firsthand scheduling, billing, and treating public aid patients while providing
      patients with an additional source for oral health care. The Heartland Dental
      Clinic model represents a cost effective method for increasing oral health access
      to underserved populations while also benefiting students in an educational
      program.

PMID- 14596166
TI  - Mental illness and the dental patient.
AB  - Virtually every oral health care practice includes patients with mental illness.
      This continuing education (CE) course gives a practical overview of common
      psychiatric disorders, their effects on oral and dental health, and conditions
      associated with mental illness that affect oral health treatment. Following a
      brief description of mental illnesses, information on conducting a mental health
      interview and making a psychiatric referral are provided. Oral health problems
      associated with mental illness and factors affecting treatment delivery are
      discussed, as well as ideas for avoiding potentially dangerous medication
      interactions and working with fearful, suspicious, or cognitively impaired
      patients. Ways in which dental hygienists can work with case managers to provide
      much needed oral health care to patients whose illness is severe or chronic are
      covered. Examples are given of work with clients illustrating principles
      described in the text. The purpose of this course is to provide oral health
      personnel the information they need to knowledgeably care for patients who have
      mental illness. Successful completion will be assessed with a post-test to be
      completed after reading the article in its entirety, including figures and case
      reports. Two continuing education course credit hours will be awarded following
      successful completion of the post-test.

PMID- 14596167
TI  - HIPAA privacy regulations clarified: let calm prevail.
AB  - The Health Insurance Portability and Accountability Act (HIPAA) privacy
      regulations are now in full effect. Enforcement regulations have been published.
      Physicians, like other Covered Entities, must come to grips with the practical
      applications and implications of the regulations in their day-to-day practice
      operations. Despite reams of prefatory guidance from the Department of Health and
      Human Services (HHS) and additional guidance from its Office for Civil Rights
      (OCR) in the form of responses to Frequently Asked Questions, the regulations
      leave much to interpretation (see http://www.hhs.gov/ocr/index.html). Many
      attorneys and consultants have raised general alarms about the dire complexity
      and impact of the privacy rules. These are unnecessary hysterics. Fortunately,
      for physician practices, most privacy issues can be dealt with by adopting
      appropriate common sense policies and procedures. This article identifies some
      common conundrums and issues physician practices are likely to encounter in
      implementing the regulations and offers practical guidance for addressing them.

PMID- 14596168
TI  - Preparing the front office staff to carry out HIPAA privacy procedures.
AB  - Although training is one way to ensure compliance with new HIPAA privacy rules,
      awareness is only the first step in preparing front office staff for implementing
      procedures related to the new rules. Role-based training is required to empower
      staff to carry out specific HIPAA privacy procedures. Each procedure offers
      options for training content, and the use of training tools with actual script is
      recommended as one method to clearly define expectations of staff when applying
      the procedures.

PMID- 14596169
TI  - Office gossip: a surprising source of liability.
AB  - Rumors and gossip are inevitable ingredients of work life. Within limits, they
      may have some beneficial functions. Still, practitioners and managers must be
      aware of the dangers inherent in defamation of character and harassment. This
      article defines workplace comments and activities that should be avoided and the
      employer's legal liability when situations get out of hand. It also outlines the
      manager's responsibilities and lists privacy rights that are codified by state
      and federal laws.

PMID- 14596170
TI  - Office space planning and design for medical practices, Part 4: Development
      issues.
AB  - The decision to build anew or remodel/add-on to your existing facility has been a
      tough one. After that decision was reached, the implementation of design and
      construction presented many difficult hurdles on the road to achieving a
      functional office space in a cost-effective manner. This article will continue to
      explore just how a practice proceeds with some of the further details of the
      implementation process.

PMID- 14596171
TI  - EMR pitfalls: avoiding costly purchasing mistakes.
AB  - With the increased capability and lower costs of computer technology, physicians
      and medical institutions are adopting electronic medical records as a means of
      improving practice efficiency and achieving both better patient care and monetary
      savings. We are very much in favor of transforming office activities onto
      electronic formats. However, there are some caveats that merit attention. This
      article discusses some of the pitfalls and pratfalls incorporating electronic
      records in into everyday practice.

PMID- 14596172
TI  - The electronic medical record in multi-site family practice, Part 1: The planning
      phase.
AB  - Electronic medical records (EMRs) are being successfully implemented on a regular
      basis. They provide real benefits. This article presents a detailed explanation
      of how this medical group implemented and created a paperless medical practice
      environment and an electronic medical record. This includes an explanation of
      hardware and software components, the method of creating the EMR, benefits,
      pitfalls, and effect on the practices.

PMID- 14596173
TI  - Dragon Naturally Speaking and ViaVoice face-off.

PMID- 14596174
TI  - Organizing a practice retreat.
AB  - Medical practices are often so busy that physicians and their staff have
      difficulty seeing the big picture. A well-organized practice retreat can provide
      needed time and space for tackling large practice management problems and
      establishing new goals. In addition, a practice retreat can enable staff members
      to get to know each other better and learn new ways to function as a cohesive
      team. In this article, the author describes the similarities and differences
      between single-task and team-building retreats. In addition, the author shares
      practical do's and don'ts for organizing worthwhile medical practice retreats and
      makes suggestions about possible locations for retreats, recommended follow-up,
      and team-building exercises.

PMID- 14596175
TI  - Has the legal atmosphere for "managed care" forever changed? Impact of the
      limitations on ERISA.

PMID- 14596176
TI  - Trends in the consumer price index.

PMID- 14596177
TI  - Increasing physician productivity using a physician extender: a study in an
      outpatient group practice at the Mayo Clinic.
AB  - Physician extenders (PE) can perform some tasks usually performed by a physician.
      Time recouped by physicians using a PE may increase physician productivity and
      physician professional satisfaction. A prospective study was completed using a PE
      in an outpatient general medical group practice setting to reduce physician
      indirect patient care, such as responding to patient telephone calls, refilling
      prescriptions, triage, and order entry. Physicians using a PE had increased
      productivity relative to physicians who did not use a PE. Physician satisfaction
      with the PE model was excellent. A physician extender may improve physician
      productivity by performing indirect patient care usually performed by physicians.

PMID- 14596178
TI  - The politics of belonging and intercultural health care.
AB  - Belonging was one of the recurrent themes in an ethnography examining the social
      context of intergroup health care relations. Certain people, both patients and
      health care providers, were constructed as belonging in the social fabric of
      health care, whereas some were left on the margins and constructed as Other. In
      this article, the theme of belonging is explored through a multilayered analysis
      of the contexts of intergroup health care encounters. The macropolitics of
      belonging are situated in the larger societal setting, replete with practices
      that mark Other. Evidences of such Othering is then traced through organizational
      contexts, drawing on the exemplars of visiting hour policy, integration of
      alternative therapies, and provision of language services. Intergroup
      interactions are then reanalyzed in light of micropolitics at the individual
      nurse-patient level. The overall picture presented is one of a range of social,
      political, historical, and economic forces reproduced in everyday intercultural
      health care encounters.

PMID- 14596179
TI  - Intercultural health care as reflective negotiated practice.
AB  - This interpretive study sought to understand how intercultural health care to
      immigrants can be practically conceptualized in multicultural populations.
      Interviews were conducted with 20 Canadian health service informants, and 12
      interviews were staged during 31 months with a multicultural coordinator in an
      Australian teaching hospital. Transcripts of 11 previously conducted group
      discussions with 34 staff members from this same Australian hospital were also
      included. Interpretation was based on these data as well as on the literature and
      the author's own experience. It was concluded that intercultural health care can
      be practically conceptualized as reflective health worker practice. Through this
      practice, responsive care can be situationally negotiated between the health
      worker and the client in a framework of jointly considered needs. For
      implementation, the barriers to negotiation must be addressed.

PMID- 14596180
TI  - Using focus groups to develop culturally relevant instruments.
AB  - Recent criticism has focused on the validity of instruments used in research with
      immigrant populations. Conventional instrument development or validation
      techniques may not be adequate to determine whether an instrument is appropriate
      for use with populations who differ from those with whom the instrument was
      originally developed. This article discusses the value of using focus group
      methodology to develop instruments for use with immigrant populations using the
      example of an intergenerational conflict tool for multigenerational Chinese
      immigrant families. Involving community members through focus groups is an
      important component of instrument development that is often neglected by
      researchers. This process was critical to developing a culturally appropriate
      instrument that accurately reflected the community's life experiences. Strategies
      for conducting meaningful and successful focus groups with Chinese immigrants are
      provided. Advantages and disadvantages of using focus groups are also discussed.

PMID- 14596181
TI  - Immigrant women implementing participatory research in health promotion.
AB  - Few studies on women's health include immigrant women as participants, and fewer
      are conducted by immigrant women themselves. In this article, the authors present
      a model that allowed their full participation as researchers and authors. They
      describe their experiences using participatory research methods with Hispanic
      women in multiple ways to reach out to isolated women, collect data about
      community needs, and provide health education. They explore the advantages and
      challenges of being trained for both researcher and health educator roles,
      describe opportunities to use this approach to assess service needs, and discuss
      the potential for personal empowerment. They also report on the time commitment
      that such a bilingual project requires. In the process of interviewing
      marginalized women, they realized how much health promotion and participatory
      research complement each other. The authors conclude that combining participatory
      research with health promotion activities has promise to contribute toward
      increased empowerment of immigrant communities.

PMID- 14596182
TI  - Transforming vulnerability.
AB  - Asian American immigrant women engaged in filial caregiving are at special risk
      for health problems due to complex contextual factors related to immigration,
      cultural traditions, and role transition. This study examines the experience of
      two groups of immigrant Asian American women who are caring for older parents. A
      total of 41 women (22 Chinese American and 19 Filipino American) were interviewed
      in a study based on Strauss and Corbin's grounded theory methodology. The women
      were determined to be loyal to their traditional culture, which included strong
      filial values, while adapting to a new culture. Through the struggle of meeting
      role expectations and coping with paradox, the women mobilized personal and
      family resources to transform vulnerability into strength and well-being.

PMID- 14596183
TI  - Bosnian and Soviet refugees' experiences with health care.
AB  - Studies of refugees in the United States rarely address health the first few
      years following resettlement in part because the refugees become subsumed under
      the foreign-born or immigrant category. A national study reaffirmed the so-called
      healthy immigrant effect, but fewer sick days and less physician use may actually
      reflect access problems, economic concerns, and health beliefs or practices that
      clash with American health care. Because statistics may mask differences in
      health and why people seek professional care, it is important to combine
      qualitative and quantitative approaches. This study examined health, illness, and
      health care use patterns of refugees in Northern California using a database
      analysis, a medical record review, and an ethnographic study of the Bosnian and
      former Soviet Union refugee communities. This article describes some ethnographic
      findings from participant observation, semistructured interviews, and focus
      groups, with an emphasis on people's experiences with health care, health risk
      behaviors, and self-care.

PMID- 14596184
TI  - Social support and the significance of shared experience in refugee migration and
      resettlement.
AB  - This article examines the role of social support as a determinant of refugee well
      being and migration patterns during early resettlement. Analysis is based on
      qualitative in-depth interviews with 47 government-assisted refugees in Canada
      and 38 key informants (settlement service providers and immigration officials) in
      Canada and overseas. The study describes refugees' decision making during stages
      of migration and resettlement, from whom they seek social support in particular
      situations, what sources are appraised as most important, and what is significant
      about the support. The authors suggest that a goal of refugees support-seeking
      strategies is affirmation through shared experience.

PMID- 14596185
TI  - High-tech solutions improve care, reduce costs.

PMID- 14596186
TI  - CJD decontamination of surgical instruments.
AB  - Following the CJD protocol and decontamination processes (Table 1) as recommended
      in the Health Canada CJD Guideline will serve to prevent transmission of CJD via
      surgical instruments, "Preparation of the work area" and "safe handling of strong
      chemicals used for decontamination" are other topics that must be addressed by
      staff in the OR and SPD. The appendix offers a quick reference that summarizes
      many of the important points which staff in the OR caring for patients, and staff
      in SPD caring for instruments, need to be aware of.

PMID- 14596187
TI  - Coping with stress. Response vs. reaction.

PMID- 14596188
TI  - Tips for the working student.

PMID- 14596189
TI  - Conflict management in student associations.

PMID- 14596190
TI  - Managing conflict in the workplace.

PMID- 14596191
TI  - Managing conflict in the classroom.

PMID- 14596192
TI  - The arena.

PMID- 14596193
TI  - Dentistry: a profession or a trade?

PMID- 14596194
TI  - Dentistry's role in biodefense.

PMID- 14596195
TI  - Altoona clinic and University of Pittsburgh join forces. Partnership could serve
      as statewide model.

PMID- 14596196
TI  - Water Street Rescue Mission Dental Clinic: filling the void for Lancaster
      community.

PMID- 14596198
TI  - Renal transplantation--demystifying the process.
AB  - Successful renal transplantation is the treatment of choice for most end stage
      renal disease (ESRD) patients, improving quality of life and increasing survival
      as compared with long-term dialysis treatment. The purpose of this article is to
      explain the process of transplantation by discussing the assessment of potential
      recipients, surgical techniques, post-operative course, potential complications
      and benefits. A brief overview of immunosuppression will also be discussed.

PMID- 14596199
TI  - Pancreas/kidney transplantation: new hope for patients with end stage renal
      disease and type 1 diabetes.
AB  - For kidney transplant recipients with type 1 diabetes, there are ongoing risks
      and consequence that can complicate the quality of life after transplantation and
      present significant challenges to the patient and health care team. There is now
      an opportunity for those patients with type 1 diabetes and renal failure to treat
      both conditions with combined pancreas/kidney (P/K) transplantation. It must be
      emphasized that P/K transplantation is not a cure for renal failure and diabetes,
      rather, it is a treatment option. Successful pancreas transplantation will
      eliminate the need for insulin therapy and normalize glucose metabolism, which
      can greatly improve quality of life. This clinical article will present an
      overview of the P/K transplantation process, discuss the important role of the
      dialysis health care professional, and outline the experience of the Multi Organ
      Transplant (MOT) program of the Toronto General Hospital (TGH), University Health
      Network (UHN), Toronto, Ontario.

PMID- 14596200
TI  - New paradigms in immunosuppression.
AB  - With the decrease in donor quality and the increase in recipient co-morbidities,
      transplantation immunosuppression is changing. New paradigms in transplantation
      include co-stimulation, lymphocyte retrafficking, and inhibiting antibody
      production. With these new paradigms come new immunosuppressive agents. While
      these new agents show great promise, their use in day-to-day clinical
      transplantation remains to be seen.

PMID- 14596201
TI  - Treatment and prevention of cytomegalovirus in renal transplant patients:
      weighing the evidence.

PMID- 14596203
TI  - Medical directives, policies, and procedures.

PMID- 14596202
TI  - Living kidney donation: a comparison of laparoscopic and open flank procedures.

PMID- 14596204
TI  - Valerie Price--you can make a difference! Interview by Faye Clark.

PMID- 14596205
TI  - Treating unique patient populations and practice growth.
AB  - Developing a dental practice niche for patients with specific medical conditions
      can provide a tremendous benefit to this patient population while enhancing
      practice productivity and profits. Capitalizing on this opportunity requires
      development of comprehensive, customized patient management systems. To remain
      profitable, practice fees must be adjusted to account for the additional time and
      effort invested in serving these unique patients.

PMID- 14596206
TI  - Use of HTR synthetic bone grafts in conjunction with immediate dental implants.
AB  - Immediate placement of dental implants in fresh extraction sockets is associated
      with remaining voids around the implants and often a partial dehiscence or
      thinning of the facial alveolar plate. Nine patients had Bioplant HTR synthetic
      bone used as a ridge preservation/augmentation material in conjunction with
      immediate placement of 10 implants. Hard tissue replacement (HTR) was used to
      fill the remaining socket void and enhance the facial ridge width, and the wound
      closed as completely as possible. Dental implants were uncovered at approximately
      6 months. Measurements taken of the internal socket width and total ridge width
      at the implant placement and uncovering showed the mean internal socket width was
      maintained (7.2 mm vs 6.9 mm), and the total ridge width exhibited a mean change
      from 9.6 mm to 8.8 mm. Of the 10 implant sites, 7 showed a net increase, 2 no
      change, and 1 a decrease in overall ridge width. All 10 implants were restored
      for at least 6 months. These clinical results suggest that HTR is a useful
      adjunct in the placement of immediate dental implants for the preservation of
      ridge width and provides a good base for functional and esthetic prosthetic
      reconstruction.

PMID- 14596207
TI  - A nanotechnology composite.

PMID- 14596208
TI  - All-ceramic restorative system for esthetic implant-supported crowns: in vitro
      evaluations and clinical case report.
AB  - Patient demands for improved esthetics have prompted the development of all
      ceramic restorative systems for dental implants, but material strength and
      restorative costs have presented clinical challenges. Therefore, a new
      restorative system with tooth-shaped ceramic copings for the anterior and
      premolar jaw regions has been introduced to address these problems. Fatigue and
      17o. compression tests were conducted in vitro to assess the mechanical strength
      of the 6 tooth-shaped copings and several luting agents of the system. A case
      report on the clinical use of the components is presented. All 6 tooth-shaped
      copings significantly exceeded the range of forces associated with restoration in
      the anterior jaw. Crown-endurance limits for fatigue and 17o. compression were
      70% higher and 46% higher, respectively, than the established minimum-fatigue
      endurance limits in those categories. In clinical evaluation, the ceramic
      restorative system performed well and produced excellent results; it has
      potential for implant restorations in the anterior and premolar regions of the
      jaw.

PMID- 14596209
TI  - The use of composite resin in removable prosthodontics.
AB  - Economic, esthetic, and concerns of tooth preservation are important when
      considering bonded composite resin for the partially edentulous patient's
      prosthetic rehabilitation. This article has described the clinical success of the
      use of bonded composite resin in removable prosthodontics. Composite resin may be
      used in daily clinical practice for the restoration of abutment teeth in contour,
      vertical support, and re-establishment of a patient's vertical dimension.

PMID- 14596210
TI  - King and Pennel's free graft series: a defining moment revisited.
AB  - The free gingival graft is one of the most versatile and predictable procedures
      in current use. A review of the significant contributions leading to this
      procedure is presented. Reports of the free graft series of King and Pennel, as
      well as the reaction to its initial presentation by members of the Philadelphia
      Society of Periodontology, are introduced to the dental literature. The
      chronology of events leading to the rediscovery of the gingival graft procedure
      in the early 1960s suggests independent and nearly simultaneous clinical
      innovation took place in Sweden and the United States. Therefore, though fully
      acknowledging Hilding Bjorn's seminal contribution, substantial credit must be
      given to colleagues King and Pennel for introducing the gingival graft procedure
      to periodontics.

PMID- 14596211
TI  - Microbial adaptations and interspecies passage.

PMID- 14596212
TI  - Sick daze.

PMID- 14596213
TI  - Bandaging Baghdad.

PMID- 14596214
TI  - Single-payer: let's puncture the myths.

PMID- 14596215
TI  - Asking about medicines.

PMID- 14596216
TI  - Firm footing.

PMID- 14596217
TI  - Substance misuse and serious mental illness: spiritual care.
AB  - BACKGROUND: People with a dual diagnosis of serious mental illness and substance
      misuse may be difficult to treat. This article explores how spirituality can be
      integrated into community care plans of these patients. It highlights the
      importance of including spirituality in pre- and post-basic-education programmes.
      CONCLUSION: Nursing models that integrate the positivist, existential and
      spiritual approach to understanding and caring for those with a dual diagnosis
      should be developed. Nurses could develop support groups along the lines of
      Alcoholics Anonymous to provide support to this group of clients. The use of
      complementary therapies by those with a dual diagnosis is an area of
      possibilities. The challenge is now to integrate spirituality into the already
      established biopsychosocial approach to caring for those with a dual diagnosis.

PMID- 14596218
TI  - Using non-invasive ventilation in acute wards: Part 2.
AB  - The second part of this article on non-invasive ventilation (NIV) examines the
      use of bilevel non-invasive ventilation, discussing the differences between CPAP
      and bilevel NIV. It also focuses on how to assess and monitor patients receiving
      either CPAP or bilevel NIV, and patient outcomes.

PMID- 14596220
TI  - Exploding the myths.

PMID- 14596219
TI  - Administration of medicines. Part 1: The law and nursing.
AB  - The authors outline the legal and professional consequences for nurses of failing
      to adhere to the law relating to the administration of medications. Part 2, next
      week, will look at the biological consequences for patients of non-adherence to
      drug administration schedules.

PMID- 14596222
TI  - Medication adherence rates and drug-resistant HIV: new data.

PMID- 14596221
TI  - Standard setting.

PMID- 14596223
TI  - Issues in antiretroviral toxicity.

PMID- 14596224
TI  - Kaposi sarcoma and its changing course in HIV infection.

PMID- 14596225
TI  - Practical applications of the HIV lipodystrophy case definition.
AB  - Diagnosis of HIV-associated lipodystrophy (LD) has been limited by the absence of
      a validated case definition and the frequent lack of objective body composition
      measures. An international, objective, case-control study recruited HIV-infected,
      adult outpatients free of active AIDS, and a case definition model for LD was
      developed. The relative merits and limitations of this definition as a practical
      tool for the long-term monitoring of a patient's LD status over the duration of
      clinical treatment are discussed.

PMID- 14596226
TI  - Editorial comment: a case definition for HIV lipodystrophy--a work in progress.

PMID- 14596227
TI  - Successful treatment of hepatitis C in a patient with advanced AIDS and
      decompensated cirrhosis.
AB  - Treatment of patients coinfected with HIV and hepatitis C virus is a challenging
      area for clinicians. We report on a treatment-naive man with advanced AIDS and
      cirrhosis secondary to hepatitis C, who has been followed from the initial
      diagnosis. After presentation, he began receiving HAART. During a disseminated
      Mycobacterium avium complex infection, massive ascites refractory to standard
      treatment developed. Substitution of nelfinavir for nevirapine in his
      antiretroviral regimen led to resolution of the ascites. Although excellent
      virologic control was achieved with HAART, the patient's immunologic response
      remained blunted until the hepatitis C was successfully treated. This case
      demonstrates that in some coinfected patients, hepatitis C can be successfully
      treated at low CD4 cell counts and that hepatitis C may influence the immunologic
      status of such patients.

PMID- 14596228
TI  - Editorial comment: liver disease in the HIV-infected patient--the courage to
      treat.

PMID- 14596229
TI  - Retraction.

PMID- 14596230
TI  - Aortic stenosis, von Willebrand factor, and bleeding.

PMID- 14596231
TI  - [Medicine as literary activity].

PMID- 14596233
TI  - Commending "The effect of blood drawing techniques and equipment on the hemolysis
      of ED laboratory blood samples.".

PMID- 14596235
TI  - Bibliography. Current world literature. Cardiovascular system.

PMID- 14596234
TI  - Clostridium difficile--not just a nosocomial infection.

PMID- 14596236
TI  - Bibliography. Current world literature. Infectious diseases.

PMID- 14596239
TI  - Agricultural IP and the public sector.

PMID- 14596240
TI  - Insensitive caregivers.

PMID- 14596242
TI  - Mother may I?

PMID- 14596243
TI  - Scientific integrity.

PMID- 14596244
TI  - Root canal treatment of three-rooted maxillary first and second premolars--a case
      report.
AB  - AIM: To report the diagnosis and successful clinical management of a patient with
      anatomical variation in maxillary first and second premolars. SUMMARY: Maxillary
      premolars have a highly variable root canal morphology, but it is rare,
      especially in the second premolar, to find three canals. This article describes
      the diagnosis and clinical management of first and second premolars with three
      canals and three separate roots, drawing particular attention to radiographic
      interpretation and access refinements. KEY LEARNING POINTS: Clinicians should be
      aware of anatomical variations in maxillary premolars and be able to apply this
      knowledge in radiographic and clinical interpretation. Access cavity refinements
      may be required for stress-free entry to complex anatomy. Complex premolar
      anatomy may be predictably managed following its identification and negotiation.

PMID- 14596245
TI  - Alternatives for automated communication in research.

PMID- 14596246
TI  - Scleroderma renal crisis.

PMID- 14596249
TI  - Addressing racial and ethnic disparities in health care delivery: the purchaser's
      role.

PMID- 14596247
TI  - Elevated brain natriuretic peptide in septic patients without heart failure.

PMID- 14596250
TI  - Alternative spine.

PMID- 14596251
TI  - From the gynecology clinic...in which pelvic pain was eventually discovered to be
      the result of an occult disc space infection at a previously fused segment.

PMID- 14596252
TI  - Preclinical data released on PI.

PMID- 14596253
TI  - Pfizer announces free drug program.

PMID- 14596254
TI  - Emtriva gets approval.

PMID- 14596255
TI  - Adherence program developed.

PMID- 14596256
TI  - Peptide may help with fat accumulation.

PMID- 14596258
TI  - Injection drug use site sanctioned.

PMID- 14596257
TI  - Bisexual partners behind HIV risk.

PMID- 14596259
TI  - Transplant study underway.

PMID- 14596260
TI  - Cannabis abuse and oral health care: review and suggestions for management.

PMID- 14596261
TI  - Recurrent oral ulceration.

PMID- 14596262
TI  - The bio-psycho-social approach to health and disease.

PMID- 14596263
TI  - Biblical pain: did Jacob have sciatica?

PMID- 14596264
TI  - Hepatitis B: Implications for the oral health worker.

PMID- 14596265
TI  - Spine care and depression.

PMID- 14596266
TI  - Hepatitis C: Implications for the oral health worker.

PMID- 14596267
TI  - Defining the problems in medical malpractice.

PMID- 14596268
TI  - From the imaging department...extreme kyphosis: stable after all these (72)
      years.

PMID- 14596269
TI  - Infant vesicoureteral reflux: a comparison between patients presenting with a
      prenatal diagnosis and those presenting with a urinary tract infection.

PMID- 14596270
TI  - [Pulse oximetry and capnography].
AB  - Noninvasive methods of monitoring are crucial in the management of intensive care
      patients, especially in the pediatric field. Pulse oxymetry measures arterial
      oxygen saturation in severely ill patients, allows oxygen requirements to be
      adjusted to the patient, reduces invasive gasometric studies and achieves
      continuous monitoring of the critically ill child. Motion and deficient tissular
      perfusion reduce the accuracy of the measured values, but more sophisticated
      pulse oximeters are more effective in preventing these artifacts. Capnometers are
      an excellent method of measuring end-tidal CO2 values in real time in intubated
      patients. Capnography produces a graphic curve of end-tidal CO2 while capnometry
      provides a numerical representation of this concentration. This technique is
      highly useful in the continuous monitoring of various respiratory problems and
      situations such as weaning or checking the correct placement of endotracheal
      cannulas.

PMID- 14596271
TI  - Problems in estimating mosquito infection rates using minimum infection rate.

PMID- 14596272
TI  - Reflections on the Anopheles gambiae genome sequence, transgenic mosquitoes and
      the prospect for controlling malaria and other vector borne diseases.
AB  - The completion of the Anopheles gambiae Giles genome sequencing project is a
      milestone toward developing more effective strategies in reducing the impact of
      malaria and other vector borne diseases. The successes in developing transgenic
      approaches using mosquitoes have provided another essential new tool for further
      progress in basic vector genetics and the goal of disease control. The use of
      transgenic approaches to develop refractory mosquitoes is also possible. The
      ability to use genome sequence to identify genes, and transgenic approaches to
      construct refractory mosquitoes, has provided the opportunity that with the
      future development of an appropriate genetic drive system, refractory transgenes
      can be released into vector populations leading to nontransmitting mosquitoes.
      An. gambiae populations incapable of transmitting malaria. This compelling
      strategy will be very difficult to achieve and will require a broad substantial
      research program for success. The fundamental information that is required on
      genome structure, gene function and environmental effects on genetic expression
      are largely unknown. The ability to predict gene effects on phenotype is
      rudimentary, particularly in natural populations. As a result, the release of a
      refractory transgene into natural mosquito populations is imprecise and there is
      little ability to predict unintended consequences. The new genetic tools at hand
      provide opportunities to address an array of important issues, many of which can
      have immediate impact on the effectiveness of a host of strategies to control
      vector borne disease. Transgenic release approaches represent only one strategy
      that should be pursued. A balanced research program is required.

PMID- 14596273
TI  - Reassessment of the role and utility of wind in suppression of mosquito (Diptera:
      Culicidae) host finding: stimulus dilution supported over flight limitation.
AB  - In a Central Michigan wetland setting, with abundant Aedes vexans (Meigen),
      Anopheles walkeri (Theobald), and Coquillettidea perturbans (Walker), electric
      fan-generated wind strongly reduced mosquito catches in Centers for Disease
      Control and Prevention light traps releasing carbon dioxide at 650 or 1,950
      ml/min. This relationship was negatively logarithmic over the range of velocities
      tested (0 m/s to 3.7 m/s; 0-8.3 mph) and closely matched the theoretical dilution
      function predicted to occur with increasing wind flows over a constantly
      releasing point source of volatile chemical. Tripling the carbon dioxide release
      rate consistently doubled the number of mosquitoes caught across the range of
      wind velocities tested. Neither applied wind velocity nor carbon dioxide release
      rate was correlated with mosquito body mass across the range of wind velocities
      tested. Collectively, these data support the conceptual model that applied wind
      diminishes mosquito catches primarily by diluting attractants rather than by
      exceeding mosquito flight capability. Previously published estimates of maximum
      air speeds of which mosquitoes are capable may now need to be reassessed if they
      were based upon shut-down of catches in traps baited with chemical attractants.
      Addition of DEET vapor significantly reduced the number of mosquitoes caught
      relative to equivalently moving air without repellent. We recommend that fan
      generated wind should be pursued as a practical means of protecting humans or
      pets from mosquitoes in the backyard setting.

PMID- 14596274
TI  - The taxonomic status of genetically divergent populations of Lutzomyia
      longipalpis (Diptera: Psychodidae) based on the distribution of mitochondrial and
      isozyme variation.
AB  - The sand fly, Lutzomyia longipalpis (Lutz & Neiva) reputedly is a complex of
      cryptic species; however, there is currently no consensus as to the number of
      species in the complex or their geographic distributions. We conducted
      phylogenetic analyses of 31 populations from throughout the species range, using
      seven isozyme loci and genes in the mitochondrial genome. Analyses of these two
      independent sets of markers were largely concordant and revealed four distinct
      clades that support the existence of four species. The four clades have distinct
      geographic ranges: (1) Brazil (Species A = Lu. longipalpis sensu stricto), (2)
      Laran (Species B = Lu. pseudolongipalpis), (3) cis-Andean (Species C), and (4)
      trans-Andean (Species D). The cis-Andean clade may be subdivided further into two
      groups, one in Colombia and one in northwestern Venezuela, but their taxonomic
      status remains unresolved. Knowledge that Lu. longipalpis is a complex of species
      may ultimately shed light on anomalies in the epidemiology of visceral
      leishmaniasis in the New World.

PMID- 14596275
TI  - In vivo and in vitro rearing of Pediculus humanus capitis (Anoplura:
      Pediculidae).
AB  - Four geographically distinct colonies of the human head louse, Pediculus humanus
      capitis De Geer (Anoplura: Pediculidae) were reared on a live host and exhibited
      significantly different life history patterns. Florida head lice exhibited
      approximately 10% slower development and approximately 15% reduced longevity
      relative to California or Ecuador head lice. Fecundity (4.9 +/- 0.2
      eggs/female/d) and fertility (76.4 +/- 2.9% mean hatching rate) declined over the
      lifetime of female lice, especially when separated from males (i.e., unmated
      recently). All four colonies (above plus one from Panama) were similar in their
      ability to tolerate starvation, although older stages tended to die sooner. An in
      vitro feeding apparatus was developed to rear head lice. Teneral first instar
      lice were placed on human hair tufts on the upper side of membrane-covered
      feeders, which were immersed bottom-side down within a vessel containing warmed
      human blood. Relative to lice reared on a human host, in vitro-reared lice
      required a significantly longer time (10-20%) to molt and survived a
      significantly shorter time as adults (30-50%); the addition of antibiotics did
      not adversely affect louse development. Teneral first instars were more likely
      than any other stage to feed through the membrane. Lice spent a significantly
      greater proportion of time searching in the in vitro apparatus than on a host,
      but the proportion of time spent feeding did not differ. This research is the
      first to demonstrate that head lice can be reared successfully in vitro through a
      complete life cycle.

PMID- 14596276
TI  - Seasonal malaria transmission and variation of anopheline density in two distinct
      endemic areas in Brazilian Amazonia.
AB  - Studies on seasonal anopheline fauna variation were performed in two distinct
      settlements in the State of Rondonia, Brazil: one at the Madeira River banks
      (Portuchuelo) with stable native Amazonian population; the other at an inland
      lumber-extracting farm (Urupa) in dry land, in which adults are mostly migrants.
      During a 6-yr period (1994-2000), 8,638 adult anophelines were collected: 2,684
      in Urupa and 5,954 in Portuchuelo. Anopheles darlingi represented >95% of total
      mosquitoes caught. Dissection of 4,424 A. darlingi females yielded a very low
      sporozoite infection index below 0.1%. Oocysts were found in both localities in
      approximately 0.1% of dissected mosquitoes. Determination of the hour biting
      rates disclosed seasonal variations in both localities. However, in Portuchuelo,
      mosquito density peaked at the acme of the rainy season, whereas at Urupa it
      peaked in the dry season. The increase in mosquito density and incidence of
      malaria cases were coincident. The high mosquito densities observed in the
      riverine settlement of Portochuelo sector B, which permits evaluation in > 10,000
      mosquitoes' bites/person/year, could explain, in spite of the low mosquito's
      infection index, the previously described development of natural immunity in the
      local population that is not observed in the dry land agroindustrial settlement
      of Urupa.

PMID- 14596277
TI  - Reduced abundance of Ixodes scapularis (Acari: Ixodidae) and the tick parasitoid
      Ixodiphagus hookeri (Hymenoptera: Encyrtidae) with reduction of white-tailed
      deer.
AB  - The principal vector for the pathogens of Lyme disease, human granulocytic
      ehrlichiosis, and human babesiosis is the tick Ixodes scapularis Say. A chalcid
      wasp, Ixodiphagus hookeri, in the family Encyrtidae parasitizes populations of
      the tick on several islands or other geographically isolated sites in New England
      with high densities of these ticks and white-tailed deer (Odocoileus
      virginianus), the principal host for adult I. scapularis. Deer densities were
      reduced at a forested tract in Bridgeport and the Bluff Point Coastal Reserve in
      Groton, Connecticut, from levels exceeding 90 animals per km2 in 1992
      (Bridgeport) and 1994 (Bluff Point) to 17 and 10 animals per km2, respectively,
      by fall 2001. Tick densities declined with sustained reductions in the population
      of white-tailed deer. Similarly, prevalence of tick parasitism by Ixodes hookeri
      declined at both sites from 30 to 25% to <1.0% and was significantly correlated
      with previous year's deer density at both sites (r(s) = 0.933 and r(s) = 0.867, P
      < or = 0.0001) and with nymphal tick densities at Bridgeport (r(s) = 0.867, P <
      or = 0.0001), but was not as well correlated with tick densities in Groton. The
      virtual disappearance of I. hookeri in this study corresponds with a lack of I.
      hookeri in mainland I. scapularis at comparable deer and tick densities,
      suggesting that there is a threshold deer density of approximatley 10-20/km2,
      with corresponding tick densities necessary for I. hookeri to successfully
      parasitize I. scapularis.

PMID- 14596278
TI  - Synergistic attraction of Aedes aegypti (L.) to binary blends of L-lactic acid
      and acetone, dichloromethane, or dimethyl disulfide.
AB  - Kairomones produced by humans provide female anthropophilic mosquitoes with vital
      cues used in host-seeking for a blood meal. These chemicals are emanated
      primarily by the skin and provide the mosquitoes a means to orient themselves to
      humans at a relatively close range. Chemical studies of these emanations have
      provided new ideas for the formulation of attractant blends. We report mosquito
      attraction responses for three binary blends and their separate components. The
      blends are comprised of L-lactic acid plus either acetone, dichloromethane, or
      dimethyl disulfide. At the emission rates used in our bioassays, these blends
      synergistically attract laboratory-reared female Aedes aegypti. Carbon dioxide is
      not a necessary component to yield high levels of attraction with these blends.
      It is postulated that at least one of these synergistic blends (L-lactic acid and
      acetone) produces mosquito attraction behavior similar to L-lactic acid and CO2.

PMID- 14596279
TI  - Influence of sugar availability and indoor microclimate on survival of Anopheles
      gambiae (Diptera: Culicidae) under semifield conditions in western Kenya.
AB  - The influence of indoor microclimate on survival of female Anopheles gambiae
      sensu stricto Giles (Diptera: culicidae) mosquitoes fed on different nutrition
      sources was evaluated in a semifield experimental hut exposed to ambient climate
      in western Kenya. Cages of mosquitoes (n approximately 50 per cage) were placed
      in nine positions within the hut combining three different sides and three
      different heights. At each height and side, mosquitoes were offered either human
      blood (once every 2 d), glucose (6% wt:vol) or a combination of the two diets
      over three experiments so that each cage position received one diet source. The
      effect of diet on survival was significant with mean survival times of 14 d for
      mosquitoes fed blood alone, 29 d for sugar alone and 33 d for blood plus sugar.
      Sugar availability decreased the odds of mortality approximately 85% compared
      with the blood group. Micro heterogeneities of temperature but not relative
      humidity also influenced survival although to a much lesser extent. The side but
      not height within the hut at which mosquitoes were placed, influenced survival
      but could not be explained by either temperature or relative humidity
      differences. The potential influence of seemingly minor heterogeneities of indoor
      microclimate upon vector longevity and vectorial capacity may merit further
      investigation. Also, the availability of sugar was shown to be a potentially
      crucial determinant of vectorial capacity. Compared with blood alone, the
      availability of sugar served to increase survival potential of vectors beyond
      ages at which they are old enough to transmit malaria.

PMID- 14596280
TI  - A survey of the Anopheles funestus (Diptera: Culicidae) group of mosquitoes from
      10 sites in Kenya with special emphasis on population genetic structure based on
      chromosomal inversion karyotypes.
AB  - We sampled Anopheles funestus Giles mosquitoes from 10 sites in Kenya to
      determine (1) the different members of this group present at these sites and (2)
      the population genetic structure of these species based on chromosomal inversion
      karyotypes with particular reference to the role of the Eastern arm of the Great
      Rift Valley and geographical distance as barriers to gene flow. Four members of
      this species group, namely An. funestus s.s., An. parensis, An. leesoni, and An.
      rivulorum, were found. An. funestus was found almost exclusively inside human
      dwellings while An. rivulorum was found almost exclusively outdoors. An. parensis
      was found both indoors and outdoors in comparable proportions. Earlier attempts
      to collect this group of mosquitoes from two of the sites yielded no mosquitoes,
      suggesting that numbers of mosquitoes change during the year, sometime reaching
      zero or very near zero. Significant levels of differentiation were observed among
      some An. funestus s.s. populations studied. Results suggest that the Rift Valley
      acts as a barrier to gene flow for An. funestus, but that levels of
      differentiation are not associated with the geographical distance between
      populations. The results are discussed in the light of the fact that inversions
      may have some adaptive significance to differences in environmental conditions.

PMID- 14596281
TI  - Susceptibility profile of Culex quinquefasciatus (Diptera: Culicidae) to Bacillus
      sphaericus on selection with rotation and mixture of B. sphaericus and B.
      thuringiensis israelensis.
AB  - Several strains of Bacillus sphaericus (Neide) (Bsph), a spore-forming bacterium
      that produces potent mosquitocidal toxins, have been widely used against mosquito
      larvae globally. In some locations in the field and in the laboratory, moderate
      to high levels of resistance in Culex pipiens complex mosquito larvae to Bsph
      have been reported. Practical strategies for dealing with the resistance problem
      and more importantly to delay or possibly prevent development of resistance to
      Bsph in the first place are urgently needed. From published reports, we deduced
      that Bsph-resistant mosquito larvae are completely susceptible to Bacillus
      thuringiensis ssp. isreaelensis (Bti) and that there is no appearance of cross
      resistance to Bti. On the basis of this information, we hypothesized that Bti
      offers a good potential for the management of resistance to Bsph, especially when
      it comes to delaying or preventing emergence of resistance. We conducted
      laboratory studies to see whether rotation of Bsph and Bti or mixture of both
      delays or prevents resistance development in Bsph-susceptible California Cx.
      quinquefasciatus. Development of resistance using Bsph alone increased after F15
      and fluctuated slightly on further selections. Rotation of Bsph and Bti resulted
      in much higher level and rapid emergence of resistance to Bsph. However,
      selection with mixtures of Bti and Bsph for 36 generations showed no emergence of
      resistance. On the basis of this information, we believe mixtures have a good
      potential in delaying or preventing Bsph resistance.

PMID- 14596282
TI  - Efficacy and longevity of nitenpyram against adult cat fleas (Siphonaptera:
      Pulicidae).
AB  - Nitenpyram (Capstar) is a fast acting, orally administered flea treatment that is
      absorbed into the blood of the host animal and is readily available for uptake by
      feeding fleas. We examined the efficacy of a single dose of nitenpyram against
      adult cat fleas, Ctenocephalides felis (Bouche), over several days. We recorded
      adult flea mortality and flea egg production on treated and untreated cats.
      Nitenpyram provided 100% kill of all fleas on the host at the time of treatment
      and for up to 24 h after treatment. Between 24 and 48 h after treatment, there
      was a 98.6% reduction in adult flea numbers. From 48 to 72 h, there was a 5%
      reduction in adult fleas. There was a 97% reduction and 95.2% reduction in the
      number of flea eggs collected from treated versus untreated animals during the
      first 48 h and from 48 to 72 h, respectively. In addition, we quantified three
      distinct behavioral responses of infested adult cats treated with nitenpyram to
      determine the extent of any immediate, overt behavioral responses in treated
      animals. A significant increase in scratching, biting, licking, and twitching
      occurred for 5 h. The biting and licking continued for 7 h after treatment.
      Administration of nitenpyram provides an effective mechanism to eliminate adult
      fleas from hosts for up to 48 h after treatment.

PMID- 14596283
TI  - Host associations of the tick, Ixodes angustus (Acari: Ixodidae), on Alaskan
      mammals.
AB  - Infestation parameters are presented for 227 ticks, all Ixodes angustus Neumann,
      collected from individual mammals (n = 531) in southeastern and south-central
      Alaska from 1996 to 1999. This tick was recovered from 12 of the 19 mammal
      species examined, with four species of shrews (Sorex spp.), two species of voles
      [Clethrionomys gapperi (Vigors) and Clethrionomys rutilus (Pallas)], one species
      of mouse [Peromyscus keeni (Rhoads)], and the red squirrel [Tamiasciurus
      hudsonicus (Erxleben)] being the most frequently parasitized hosts. Larvae (n =
      146) of I. angustus were collected most often, followed by nymphs (n = 50),
      females (n = 30), and a single male. The leptinid mammal-nest beetle Leptinus
      occidentamericanus Peck (1 male, 5 females) was also recovered from five
      individual small mammals; three of these were C. rutilus.

PMID- 14596284
TI  - Experimental infection of lone star ticks, Amblyomma americanum (L.), with
      Rickettsia parkeri and exposure of guinea pigs to the agent.
AB  - The maculatum agent, Rickettsia parkeri (a member of the spotted fever group
      rickettsiae), was inoculated into a colony of the lone star tick, Amblyomma
      americanum, and followed for two tick generations. In addition, guinea pigs were
      exposed to the agent by direct injection and by feeding infected ticks on them.
      Eighty (53%) of 150 nymphal A. americanum that were inoculated with suspensions
      of R. parkeri were positive by hemolymph test and fluorescent antibody test for
      rickettsial infection when examined as adults. One-month survival of R. parkeri
      infected ticks was similar to that of control (noninfected) ticks. Transstadial
      and transovarial transmission of R. parkeri in the laboratory was demonstrated in
      A. americanum. When guinea pigs were exposed to the maculatum agent by either
      direct injection of Vero cell-grown R. parkeri, injection of homogenates of
      infected ticks, or by feeding of infected ticks, they developed mild fevers and
      occasional scrotal reactions. These data indicate that R. parkeri can remain
      viable in lone star ticks for two generations and suggest that guinea pigs may
      become infected, displaying mild clinical signs.

PMID- 14596285
TI  - Borrelia burgdorferi s.l. in Ixodes ricinus (Acari: Ixodidae) ticks collected
      from vegetation and small rodents in recreational areas of the city of Poznan.
AB  - During 1998-1999, Ixodes ricinus (L.) populations were investigated in three
      different biotopes (deciduous, mixed, coniferous forest) situated in popular
      recreational areas in Poznan, Poland. In total, 1,123 questing ticks (1,002
      nymphs, 69 males, 52 females) were collected by flagging vegetation.
      Additionally, in 1998 between May and September small rodents were trapped and
      inspected for feeding ticks. Altogether, 213 rodents of three species: Apodemus
      agrarius Pall., A. flavicollis Melchior, Clethrionomys glareolus Schreber were
      captured. Of 323 engorged ticks, 304 were larvae and 19 nymphs. All ticks
      collected from vegetation, as well as from rodents were examined for the presence
      of Borrelia burgdorferi Johnson, Schmid, Hyde, Steigenwalt & Brenner s.l.
      spirochetes by indirect immunofluorescence assay (IFA) using PAB 1B29. The
      seasonal pattern of activity of questing I. ricinus was always bimodal (May/June
      and August/September). The most abundant tick population occurred in the
      deciduous forest. The total infection rate in questing ticks was 16.2%.
      Differences in mean infection prevalence of host-seeking ticks between three
      biotopes each year were not significant. On average more larvae parasitized on
      the genus of Apodemus than on C. glareolus. 17.8% of larvae and 31.6% of nymphs
      fed on rodents harbored spirochetes. The three rodent species contributed to a
      different degree in to transmission of the pathogen to subadult stages.
      Approximately 27% of larvae infested on A. agrarius, 22% on C. glareolus, and
      only 4.2% on A. flavicollis contained spirochetes. The results suggest that the
      prevalence of A. agrarius and C. glareolus in disturbed urban forests used for
      leisure activities seems to be crucial for the maintenance of B. burgdorferi s.l.
      in I. ricinus populations.

PMID- 14596286
TI  - Sindbis virus-associated pathology in Aedes albopictus (Diptera: Culicidae).
AB  - Virus dissemination and associated pathology were examined in Aedes albopictus
      after intrathoracic inoculation of Sindbis virus (SIN), the prototypic
      Alphavirus. At 10 days postinfection, virus RNA was detected in all three-body
      segments of the insect. Colocalization of virus antigen with structural pathology
      was observed in mosquito salivary glands and midgut-associated visceral muscles,
      representing yet another example of arbovirus-associated pathology in a mosquito
      host. SIN antigen and gross pathology were detected in lateral lobes, but not the
      medial lobe of salivary glands, whereas virus antigen, vacuolated cytoplasm, and
      myofilament misalignment were detected in the visceral muscles at the midgut
      exterior surface. Early in the midgut infection, virus antigen was localized in
      small foci on the organ surface that progressed to a grate work-like banding
      pattern that eventually cleared. Both the salivary glands and the midgut are
      essential to insect survival and reproduction. Additionally, these organs provide
      a pathway for virus transmission in nature. Although SIN infection may not
      shorten the mosquito life span, persistent coexistence could permit survival of
      both host and microbe as well as contribute to alterations in insect behavior.

PMID- 14596287
TI  - Relationship between altitude and intensity of malaria transmission in the
      Usambara Mountains, Tanzania.
AB  - There is a consensus that malaria is a growing problem in African highlands. This
      is surprising because many parts of the highlands were considered too cold to
      support transmission. In this report, we examined how transmission of Plasmodium
      falciparum in six villages changed along an altitude transect in the Usambara
      Mountains, Tanzania, from 300 m to 1700 m. Routine entomological collections were
      made using spray catches and light traps for 15 mo. Direct estimates of
      entomological inoculation rates and indirect estimates of vectorial capacity
      suggested a >1000-fold reduction in transmission intensity between the
      holoendemic lowland and the hypoendemic highland plateau. Lowland transmission
      was perennial with a significant peak in the cool season after the long rains in
      May, when vectors densities were high. In the highlands, low temperatures
      prevented parasite development in mosquitoes during the cool season rains, and
      highland transmission was therefore limited to the warm dry season when vector
      densities were low. The primary effect of increasing altitude was a log-linear
      reduction in vector abundance and, to a lesser extent, a reduction in the
      proportion of infective mosquitoes. Highland malaria transmission was maintained
      at extraordinarily low vector densities. We discuss herein the implications of
      these findings for modeling malaria and suggest that process-based models of
      malaria transmission risk should be improved by considering the direct effect of
      temperature on vector densities. Our findings suggest that variation in the short
      rains in November and changes in agricultural practices are likely to be
      important generators of epidemics in the Usambaras.

PMID- 14596288
TI  - Treatment of black-tailed prairie dog burrows with deltamethrin to control fleas
      (Insecta: Siphonaptera) and plague.
AB  - Burrows within black-tailed prairie dog (Cynomys ludovicianus) colonies on the
      Rocky Mountain Arsenal National Wildlife Refuge, Colorado, were dusted with
      deltamethrin insecticide to reduce flea (Insecta: Siphonaptera) abundance. Flea
      populations were monitored pre- and posttreatment by combing prairie dogs and
      collecting fleas from burrows. A single application of deltamethrin significantly
      reduced populations of the plague vector Oropsylla hirsuta, and other flea
      species on prairie dogs and in prairie dog burrows for at least 84 d. A plague
      epizootic on the Rocky Mountain Arsenal National Wildlife Refuge caused high
      mortality of prairie dogs on some untreated colonies, but did not appear to
      affect nearby colonies dusted with deltamethrin.

PMID- 14596290
TI  - A cautionary note: survival of nymphs of two species of ticks (Acari: Ixodidae)
      among clothes laundered in an automatic washer.
AB  - Host-seeking ticks often remain on clothing of persons returning home from work
      or recreation in tick habitats, and can pose at least a temporary risk to people
      and pets in these homes. Laundering clothing has been one of the recommendations
      to reduce tick exposure. Host-seeking lone star tick, Amblyomma americanum (L.),
      and blacklegged tick, Ixodes scapularis Say, nymphs confined in polyester mesh
      packets, were included with laundry in cold, warm, and hot wash cycles of an
      automatic clothes washer. Ticks were also placed with washed clothing and
      subjected to drying in an automatic clothes dryer set on high heat and on air
      only (unheated). Most nymphs (> or = 90%) of both species survived the cold and
      warm washes, and 95% of A. americanum nymphs survived the hot wash. At the time
      of their removal from the washer, I. scapularis nymphs were clearly affected by
      the hot wash, but 65% were considered alive 20-24 h later. Large percentages of
      nymphs of both species survived hot washes in which two other detergents (a
      powder containing a nonchlorine bleach and a liquid) were used. All ticks were
      killed by the 1 h cycle at high heat in the clothes dryer, but with unheated air
      some nymphs of both species survived the 1 h cycle in the dryer. Given the
      laundering recommendations of clothing manufacturers and variation in the use
      automatic clothes washers, laundry washed in automatic washers should not be
      considered free of living ticks.

PMID- 14596289
TI  - Detection and identification of pathogens and host DNA in unfed host-seeking
      Ixodes ricinus L. (Acari: Ixodidae).
AB  - In this study, we have developed molecular methods for the identification of
      reservoir hosts of sylvatic tick-borne zoonoses. The methods are based on the
      analysis of the blood meal remnant in the tick gut and include detection of
      pathogens and identification of the host origin of the blood meal. For host
      identification, a universal primer pair was used to amplify part of the
      vertebrate 18S rRNA gene followed by reverse line blot hybridization using
      subgroup-specific probes. Analyses of DNA from whole blood of vertebrates
      identified the correct subgroup of a broad range of vertebrate species (e.g.,
      Ruminantia, Leporidea, Canidae, Murinae, Arvicolinae, Insectivora, Galliformes,
      Passeriformes) using probes based on the 18S rDNA sequences. Host DNA in the
      remnants of larval blood meals was detected in the gut of Ixodes ricinus nymphs
      maintained under natural conditions up to 9 mo after molting. For pathogen
      identification, a multiplex polymerase chain reaction was used that targeted
      parts of the 18S rRNA gene of piroplasm protozoa, the 16S rRNA gene of bacteria,
      and the intergenic spacer of the Borrelia burgdorferi genospecies complex. The
      utility of both methods was demonstrated under laboratory conditions by detecting
      Babesia microti (Franca) and gerbil DNA in 3-mo-old I. ricinus nymphs that had
      fed on B. microti-infected gerbils as larvae, and under field conditions by
      analyzing unfed ticks that were collected in a forest. The field study showed
      that the majority of ticks had fed on ruminants or birds and few on rodents,
      which is in accord with our knowledge of the fauna in this forest. Few pathogens
      were detected but the discovery of Borrelia valaisiana and B. burgdorferi s.s. in
      ticks that had fed on deer and Borrelia afzelii in a tick that had fed on a bird
      raises questions about the mode of transmission of these spirochetes and possibly
      about their host specificity.

PMID- 14596291
TI  - Free-standing, self referral centers for whole-body CT screening should be
      closed, or at least restricted to at-risk patients. For the proposition.

PMID- 14596293
TI  - Semiautomated segmentation of blood vessels using ellipse-overlap criteria:
      method and comparison to manual editing.
AB  - Two-dimensional intensity-based methods for the segmentation of blood vessels
      from computed-tomography-angiography data often result in spurious segments that
      originate from other objects whose intensity distributions overlap with those of
      the vessels. When segmented images include spurious segments, additional methods
      are required to select segments that belong to the target vessels. We describe a
      method that allows experts to select vessel segments from sequences of segmented
      images with little effort. Our method uses ellipse-overlap criteria to
      differentiate between segments that belong to different objects and are separated
      in plane but are connected in the through-plane direction. To validate our
      method, we used it to extract vessel regions from volumes that were segmented via
      analysis of isolabel-contour maps, and showed that the difference between the
      results of our method and manually-edited results was within inter-expert
      variability. Although the total editing duration for our method, which included
      user-interaction and computer processing, exceeded that of manual editing, the
      extent of user interaction required for our method was about a fifth of that
      required for manual editing.

PMID- 14596294
TI  - Investigation of new psychophysical measures for evaluation of similar images on
      thoracic computed tomography for distinction between benign and malignant
      nodules.
AB  - We have been developing a computerized scheme to assist radiologists in improving
      the diagnostic accuracy for lung cancers on low-dose computed tomography (LDCT)
      scans by use of similar images for malignant nodules and benign nodules. A
      database of 415 LDCT scans including 73 cases with 76 confirmed cancers and 342
      cases with 413 confirmed benign nodules was first collected in an LDCT screening
      program for early detection of lung cancers in Nagano, Japan. An observer study
      by use of receiver operating characteristics analysis was first conducted with
      five radiologists to demonstrate that presenting similar images for malignant
      nodules and benign nodules can significantly improve radiologists' performance in
      the diagnosis of unknown nodules. Another observer study was then conducted for
      obtaining reliable data on subjective similarity ratings by 10 radiologists.
      Based on the subjective similarity ratings, three important features were
      selected from a number of nodule features, and four different techniques for the
      determination of similarity measures, namely, a feature-based technique, a pixel
      value-difference based technique, a cross-correlation-based technique, and a
      neural-network-based technique, were investigated and evaluated in terms of the
      correlation coefficient with the subjective similarity ratings. The experimental
      results in this study indicated that the neural-network-based technique can
      provide a reliable psychophysical similarity measure which is comparable to the
      subjective similarity ratings for a single radiologist when evaluated by use of
      correlation with the average similarity ratings for the other nine radiologists.

PMID- 14596295
TI  - Conceptus radiation dose assessment from fluoroscopically assisted surgical
      treatment of hip fractures.
AB  - Our aims in the present study were to (a) provide normalized dose data for the
      estimation of the conceptus dose from fluoroscopically assisted surgical
      treatment of hip fractures carried out during all trimesters of pregnancy and (b)
      estimate the conceptus radiation dose and risks associated with fluoroscopy
      during a typical treatment of hip fracture performed on a pregnant woman.
      Conceptus doses normalized to entrance surface dose (ESD) or dose area product
      (DAP) were obtained with the help of anthropomorphic phantoms simulating
      pregnancy in the three trimesters of gestation. ESD and conceptus dose
      measurements were carried out using thermoluminescent dosimeters. DAP to
      conceptus dose conversion factors were estimated for the first, second and third
      trimesters of gestation. Conceptus dose data normalized to ESD were also
      estimated to investigate whether these conversion factors may be used for
      procedures carried out in x-ray units not equipped with a DAP meter.
      Fluoroscopically assisted surgical treatments were performed in 18 women. The
      projections involved in these procedures are (a) posteroanterior (PA) and (b)
      lateral crosstable 45 degrees (LC). Radiation doses for a potential conceptus
      were estimated by using normalized dose data obtained in phantoms. The results
      consist of tabulated dose data normalized to DAP or ESD for the estimation of a
      conceptus dose. An important finding of this study was that the total DAP of a
      procedure, instead of the individual DAP values of each projection, could be used
      for the accurate estimation of the conceptus dose. Conceptus doses calculated
      using dose data normalized to ESD are about 23% higher compared to those
      estimated using data normalized to DAP. This discrepancy may be attributed to the
      contribution of scattering radiation from PA projection to ESD measurement of LC
      projection and vice versa. Therefore, dose data normalized to ESD do not provide
      accurate conceptus dose estimation. Doses normalized to DAP showed a dependence
      on (a) tube potential and (b) tube filtration. Data are provided to extent the
      doses normalized to DAP for the standard spectrum to other tube voltages and
      filtrations. The maximum dose for a potential conceptus was 0.425 mGy for a
      patient irradiated for 50 seconds during the PA projection and for 40 seconds
      during the LC projection. Although the total duration of fluoroscopy is usually
      less than 2 minutes during a typical procedure, screening time as long as 14
      minutes has been reported in the literature for treatment of complex fractures.
      The relationship between conceptus dose and fluoroscopy time found in the current
      study showed that, in these cases, the radiation dose received by a conceptus may
      exceed 1 mGy. In conclusion, an accurate estimation of conceptus doses associated
      with fluoroscopically assisted surgical treatment of hip fractures can be made
      using the DAP normalized dose data provided in this study. Conceptus doses from a
      typical procedure is less than 1 mGy during all trimesters.

PMID- 14596296
TI  - Angular dependence of the luminance and contrast in medical monochrome liquid
      crystal displays.
AB  - Active-matrix liquid crystal displays (AMLCDs) are light-modulating devices that
      generate images by differentially transmitting a nearly uniform luminous field
      provided by a backlight. While emissive displays exhibit a quasi-Lambertian
      emission with almost constant contrast at off-normal viewing, the anisotropy of
      the electro-optic effect that controls light transmission in AMLCDs causes a
      pixel luminance that varies, sometimes strongly, with viewing angle. These
      variations are not identical for all gray levels and can eventually cause
      grayscale inversions. In this paper, we measured the luminance emission of a
      monochrome medical AMLCD, a medical cathode-ray tube monitor, and a color desktop
      AMLCD, using a collimated photopic probe positioned on a manual rotation arm, and
      a research radiometer with automatic readout. The probe measures luminance with a
      small acceptance angle and provides optical shielding from emissions at other
      viewing directions that contaminate the readings. We obtained luminance response
      curves versus angle in the vertical, horizontal and at 45 degrees diagonal
      directions. The display systems were calibrated to reflect the DICOM Part 3.14
      standard grayscale display function (GDF) when measured using the manufacturer's
      probe and software tools. We analyzed the measurements at different viewing
      directions with respect to their departure from the GDF by computing the
      normalized contrast (deltaL/L) as a function of the DICOM just-noticeable
      difference index. Although cathode-ray tubes are known to be quasi-Lambertian
      emitters, the luminance at normal viewing is higher than the luminance observed
      at large angles. This decrease in luminance is however proportionally similar for
      all gray levels, resulting in a relatively flat contrast response for all angles.
      In addition to being more pronounced, the angular variation in AMLCDs does not
      follow the same profile at different intensities with the subsequent variation in
      the achieved display contrast. The changes due to off-normal viewing are
      substantial at large angles in the horizontal and vertical directions, and much
      worse in the diagonal viewing directions.

PMID- 14596297
TI  - Evaluation of detector dynamic range in the x-ray exposure domain in mammography:
      a comparison between film-screen and flat panel detector systems.
AB  - Digital detectors in mammography have wide dynamic range in addition to the
      benefit of decoupled acquisition and display. How wide the dynamic range is and
      how it compares to film-screen systems in the clinical x-ray exposure domain are
      unclear. In this work, we compare the effective dynamic ranges of film-screen and
      flat panel mammography systems, along with the dynamic ranges of their component
      image receptors in the clinical x-ray exposure domain. An ACR mammography phantom
      was imaged using variable mAs (exposure) values for both systems. The dynamic
      range of the contrast-limited film-screen system was defined as that ratio of mAs
      (exposure) values for a 26 kVp Mo/Mo (HVL=0.34 mm Al) beam that yielded passing
      phantom scores. The same approach was done for the noise-limited digital system.
      Data from three independent observers delineated a useful phantom background
      optical density range of 1.27 to 2.63, which corresponded to a dynamic range of
      2.3 +/- 0.53. The digital system had a dynamic range of 9.9 +/- 1.8, which was
      wider than the film-screen system (p<0.02). The dynamic range of the film-screen
      system was limited by the dynamic range of the film. The digital detector, on the
      other hand, had an estimated dynamic range of 42, which was wider than the
      dynamic range of the digital system in its entirety by a factor of 4. The
      generator/tube combination was the limiting factor in determining the digital
      system's dynamic range.

PMID- 14596298
TI  - Dose model for stent-based delivery of a radioactive compound for the treatment
      of restenosis in coronary arteries.
AB  - Radiolabeled drug-eluting stents have been proposed recently as a novel method to
      potentially reduce restenosis in coronary arteries. A P-32 labeled
      oligonucleotide (ODN) loaded on a polymer coated stent is slowly released in the
      arterial wall to deliver a therapeutic dose to the target tissue. However, the
      relatively low proportion of drugs transferred to the arterial wall (<2%-5%
      typically) raises questions about the degree to which radiolabeled drugs eluted
      from the stent can contribute to the total radiation dose delivered to tissues. A
      three-dimensional diffusion-convection transport model is used to model the
      transport of a hydrophilic drug released from the surface of a stent to the
      arterial media. Large drug concentration gradients are observed near the stent
      struts giving rise to a nonuniform radiation activity distribution for the drug
      in the tissues as a function of time. A voxel-based kernel convolution method is
      used to calculate the radiation dose rate resulting from this activity build-up
      in the arterial wall based on the medical internal radiation dose formalism.
      Measured residence time for the P-32 ODN in the arterial wall and at the stent
      surface obtained from animal studies are used to normalize the results in terms
      of absolute dose to tissue. The results indicate that radiation due to drug
      eluted from the stent contributes only a small fraction of the total radiation
      delivered to the arterial wall, the main contribution coming from the activity
      that remains embedded in the stent coating. For hydrophilic compounds with rapid
      transit times in arterial tissue and minimal binding interactions, the activity
      build-up in the arterial wall contributes only a small fraction to the total dose
      delivered by the P-32 ODN stent. For these compounds, it is concluded that
      radiolabeled drug-eluting stent will not likely improve the performance of
      radioactive stents for the treatment of restenosis. Also, variability in the
      delivery efficacy of drug delivery devices makes accurate dosimetry difficult and
      the drug washout in the systemic circulatory system may yield an unnecessary
      activity build-up and dose to healthy organs.

PMID- 14596299
TI  - Half-scan fan-beam computed tomography with improved noise and resolution
      properties.
AB  - Half-scan strategy can be used for reducing scanning time and radiation dose
      delivered to the patient in fan-beam computed tomography (CT). In helical CT, the
      data weighting/interpolation functions are often devised based upon half-scan
      configurations. The half-scan fan-beam filtered backprojection (FFBP) algorithm
      is generally used for image reconstruction from half-scan data. It can, however,
      be susceptible to sample aliasing and data noise for configurations with short
      focal lengths and/or large fan-angles, leading to nonuniform resolution and noise
      properties in reconstructed images. Uniform resolution and noise properties are
      generally desired because they may lead to an increased utility of reconstructed
      images in estimation and/or detection/classification tasks. In this work, we
      propose an algorithm for reconstruction of images with uniform noise and
      resolution properties in half-scan CT. In an attempt to evaluate the image-noise
      properties, we derive analytic expressions for image variances obtained by use of
      the half-scan algorithms. We also perform numerical studies to assess
      quantitatively the resolution and noise properties of the algorithms. The results
      in these studies confirm that the proposed algorithm yields images with more
      uniform spatial resolution and with lower and more uniform noise levels than does
      the half-scan FFBP algorithm. Empirical results obtained in noise studies also
      verify the validity of the derived expressions for image variances. The proposed
      algorithm would be particularly useful for image reconstruction from data
      acquired by use of configurations with short focal lengths and large field of
      measurement, which may be encountered in compact micro-CT and radiation
      therapeutic CT applications. The analytic results of the image-noise properties
      can be used for image-quality assessment in detection/classification tasks by use
      of model-observers.

PMID- 14596300
TI  - Computation of beam quality parameters for Mo/Mo, Mo/Rh, Rh/Rh, and W/Al
      target/filter combinations in mammography.
AB  - A computer program was implemented to predict mammography x-ray beam parameters
      in the range 20-40 kV for Mo/Mo, Mo/Rh, Rh/Rh, and W/Al target/filter
      combinations. The computation method used to simulate mammography x-ray spectra
      is based on the Boone et al. model. The beam quality parameters such as the half
      value layer (HVL), the homogeneity coefficient (HC), and the average photon
      energy were computed by simulating the interaction of the spectrum photons with
      matter. The checking of this computation was done using a comparison of the
      results with published data and measured values obtained at the Netherlands
      Metrology Institute Van Swinden Laboratorium, National Institute of Standards and
      Technology, and International Atomic Energy Agency. The predicted values with a
      mean deviation of 3.3% of HVL, 3.7% of HC, and 1.5% of average photon energy show
      acceptable agreement with published data and measurements for all target/filter
      combinations in the 23-40 kV range. The accuracy of this computation can be
      considered clinically acceptable and can allow an appreciable estimation for the
      beam quality parameters.

PMID- 14596301
TI  - A method for incorporating organ motion due to breathing into 3D dose
      calculations in the liver: sensitivity to variations in motion.
AB  - Organ motion has been previously described using a probability distribution
      function that depends solely upon the amplitude of motion and the degree of
      asymmetry in the breathing cycle, and that function has been used with patient
      specific parameters to correct static dose distributions for patient breathing
      using a dose convolution method. In this study, the consequences of errors in the
      selection of those two parameters were evaluated. Patients previously treated
      using a focal liver dose escalation protocol were selected with tumors located in
      the superior or inferior portion of the liver. For a fixed degree of asymmetry
      (amplitude), the amplitude (asymmetry) of motion was varied about its nominal
      value and the consequences of organ motion on the dose distribution and the
      (potentially new) prescription dose were evaluated. These comparisons show that
      small (+/- 3 mm) variations of the amplitude of motion about the nominally
      measured value may not result in clinically significant changes (< a single
      fraction change in the prescription dose), however, larger variations (> 5 mm)
      can lead to significant changes. Assuming from measurement that the patient
      breathes asymmetrically (spends more time at expiration), variations in the
      assumed degree of asymmetry rarely lead to clinically significant changes; the
      most significant cause for concern being when the patient breathing cycle is
      maximally different from the treatment planning case (e.g., patient assumed to
      spend more time at expiration, but later breaths symmetrically). The results
      point out where quality assurance efforts should be concentrated to help assure
      the validity of the assumptions used to correct the static dose distributions for
      patient breathing using the convolution method.

PMID- 14596302
TI  - Image reconstruction and performance evaluation for ECG-gated spiral scanning
      with a 16-slice CT system.
AB  - We present an image reconstruction approach and a performance evaluation for ECG
      gate cardiac spiral scanning with recently introduced 16-slice CT equipment. We
      present an extension of the Adaptive Cardio Volume (ACV) reconstruction approach
      for ECG-gated multislice spiral scanning. We discuss the image z reformation
      introduced to control the spiral slice width of the final images and give an
      overview of the reformation functions chosen. We investigate image quality and
      discuss the maximum number of slices that can be reconstructed without severe
      cone-beam artifacts. Slice sensitivity profiles (SSPs) and transverse resolution
      are evaluated as a function of the patient's heart rate. We demonstrate the
      influence of slice width on the visualization of stents and plaques and show the
      impact of reduced gantry rotation time (0.42 s) on temporal resolution. Deviating
      from general purpose spiral scanning cone-beam reconstruction is not required for
      ECG-gated cardiac CT with up to 16 slices. Using the ACV approach with image
      reformation, SSPs are well defined and independent of the patient's heart rate.
      With 0.75 mm collimated slice width, the measured full width at half-maximum
      (FWHM) of the smallest reconstructed slice is about 0.83 mm. Using this slice
      width and overlapping image reconstruction, cylindrical holes 0.6-0.7 mm in
      diameter can be resolved in a z-resolution phantom. Adequate visualization of the
      coronary arteries requires reconstruction slice widths not larger than 1.5 mm.
      Visualization of stents and severe calcifications is significantly improved with
      sub-mm slice width. Experimental evidence for the theoretically predicted
      temporal resolution and for the variation of temporal resolution depending on the
      position in the field of measurement (FOM) is presented. With 0.42 s gantry
      rotation temporal resolution reaches its optimum of 105 ms in the center of the
      FOM at 81 bpm. First scans on human subjects demonstrate the potential to expand
      the range of heart rates accessible to routine clinical examinations. A 16-slice
      platform can cover the heart with sub-mm slices within short breath-hold times,
      allowing for improved cardiac imaging due to isotropic sub-mm spatial resolution.

PMID- 14596303
TI  - CT colonography: does improved z resolution help computer-aided polyp detection?
AB  - Multislice helical CT offers several retrospective choices of longitudinal (z)
      resolution at a given detector collimation setting. We sought to determine the
      effect of z resolution on the performance of a computer-aided colonic polyp
      detector, since a human reader and a computer-aided polyp detector may have
      optimal performances at different z resolutions. We ran a computer-aided polyp
      detection algorithm on phantom data sets as well as data obtained from a single
      patient. All data were reconstructed at various slice thicknesses ranging from
      1.25 to 10 mm. We studied the performance of the detector at various ranges of
      polyp sizes using free-response receiver-operating characteristic analyses. We
      also studied contrast-to-noise ratios (CNR) as a function of slice thickness and
      polyp size. For the phantom data, reducing the slice thickness from 5 to 1.25 mm
      improves sensitivity from 84.5% to 98.3% (all polyps), from 61.4% to 95.5%
      (polyps in the range [0, 5) mm) and from 97.7% to 100% (polyps in the range [5,
      10) mm) at a false positive rate of 20 per data set. For polyps larger than 10
      mm, there is no significant improvement in detection sensitivity when slice
      thickness is reduced. CNRs showed expected behavior with slice thickness and
      polyp size, but in all cases remained high (> 4). The results for the patient
      data followed similar patterns to that of the phantom case. Thus we conclude that
      for this detector, the optimal slice thickness is dependent upon the size of the
      smallest polyps to be detected. For detection of polyps 10 mm and larger,
      reconstruction of 5 mm sections may be sufficient. Further study is required to
      generalize these results to a broader population of patients scanned on different
      scanners.

PMID- 14596304
TI  - Fuzzy logic guided inverse treatment planning.
AB  - A fuzzy logic technique was applied to optimize the weighting factors in the
      objective function of an inverse treatment planning system for intensity
      modulated radiation therapy (IMRT). Based on this technique, the optimization of
      weighting factors is guided by the fuzzy rules while the intensity spectrum is
      optimized by a fast-monotonic-descent method. The resultant fuzzy logic guided
      inverse planning system is capable of finding the optimal combination of
      weighting factors for different anatomical structures involved in treatment
      planning. This system was tested using one simulated (but clinically relevant)
      case and one clinical case. The results indicate that the optimal balance between
      the target dose and the critical organ dose is achieved by a refined combination
      of weighting factors. With the help of fuzzy inference, the efficiency and
      effectiveness of inverse planning for IMRT are substantially improved.

PMID- 14596305
TI  - Comparison of dose calculation algorithms with Monte Carlo methods for photon
      arcs.
AB  - The objective of this study is to seek an accurate and efficient method to
      calculate the dose distribution of a photon arc. The algorithms tested include
      Monte Carlo, pencil beam kernel (PK), and collapsed cone convolution (CCC). For
      the Monte Carlo dose calculation, EGS4/DOSXYZ was used. The SRCXYZ source code
      associated with the DOSXYZ was modified so that the gantry angle of a photon beam
      would be sampled uniformly within the arc range about an isocenter to simulate a
      photon arc. Specifically, photon beams (6/18 MV, 4 x 4 and 10 x 10 cm2) described
      by a phase space file generated by BEAM (MCPHS), or by two point sources with
      different photon energy spectra (MCDIV) were used. These methods were used to
      calculate three-dimensional (3-D) distributions in a PMMA phantom, a cylindrical
      water phantom, and a phantom with lung inhomogeneity. A commercial treatment
      planning system was also used to calculate dose distributions in these phantoms
      using equivalent tissue air ratio (ETAR), PK and CCC algorithms for inhomogeneity
      corrections. Dose distributions for a photon arc in these phantoms were measured
      using a RK ion chamber and radiographic films. For homogeneous phantoms, the
      measured results agreed well (approximately 2% error) with predictions by the
      Monte Carlo simulations (MCPHS and MCDIV) and the treatment planning system for
      the 180 degrees and 360 degrees photon arcs. For the dose distribution in the
      phantom with lung inhomogeneity with a 90 degrees photon arc, the Monte Carlo
      calculations agreed with the measurements within 2%, while the treatment planning
      system using ETAR, PK and CCC underestimated or overestimated the dose inside the
      lung inhomogeneity from 6% to 12%.

PMID- 14596306
TI  - Seed loss through the urinary tract after prostate brachytherapy: examining the
      role of cystoscopy and urine straining post implant.
AB  - This study describes one institution's experience with seed retrieval through the
      urinary tract and makes recommendations for cystoscopy and urine straining post
      prostate brachytherapy (PB). 1794 patients from two separate cohorts covering
      different time periods (early versus late) were analyzed. All patients were
      preplanned with a modified peripheral loading technique and implanted with
      preloaded needles (125I or 103Pd) under ultrasound guidance. A catheter was used
      to delineate the urethra during the volume study but was not used during the
      implant. All patients underwent post implant cystoscopy. All patients were
      instructed to strain their urine for seven days post implant and return any seeds
      to our center. In our experience, seed loss through the urinary tract is a common
      event after PB, occurring in 29.7% of patients and was more common in patients
      from the early cohort, those implanted with 125I seeds or those patients with
      prior transurethral resection of the prostate. Average seed loss per case,
      however, represents only 0.58% of total activity. We continue to recommend
      routine post implant cystoscopy for seed retrieval and periprocedural management.
      We no longer recommend that patients strain their urine at home after documenting
      a low rate of seed loss after discharge.

PMID- 14596307
TI  - Custom step wedge blocking using dynamic multileaf collimation for parametrial
      pelvic boost irradiation following brachytherapy for carcinoma of the cervix.
AB  - Carcinoma of the cervix is typically treated with a combination of intracavitary
      brachytherapy and external beam radiation. The external beam dose is delivered
      with whole pelvis fields followed by split fields that protect midline organs at
      risk (bladder and rectum) while treating the parametria. Three approaches have
      been developed to shield midline structures: a simple rectangular block, a block
      customized to a single brachytherapy isodose line, and a step wedge filter
      constructed to conform to multiple brachytherapy isodose lines. A customized step
      wedge filter has the potential to produce a more homogeneous dose distribution
      but has not achieved widespread use due to labor intensive construction. We have
      developed a simple, novel method to produce a custom midline step wedge using
      dynamic multileaf collimation (dMLC). A comparison of film measurements in a
      phantom with the dose calculated by a commercial treatment planning system
      demonstrated agreement within 3% or 3 mm. The technique requires delivery times
      comparable to conventional techniques.

PMID- 14596308
TI  - The response of Kodak EDR2 film in high-energy electron beams.
AB  - Kodak XV2 film has been a key dosimeter in radiation therapy for many years. The
      advantages of the recently introduced Kodak EDR2 film for photon beam dosimetry
      have been the focus of several IMRT verification dosimetry publications. However,
      no description of this film's response to electron beams exists in the
      literature. We initiated a study to characterize the response and utility of this
      film for electron beam dosimetry. We exposed a series of EDR2 films to 6, 9, 12,
      16, and 20 MeV electrons in addition to 6 and 18 MV x rays to develop standard
      characteristic curves. The linac was first calibrated to ensure that the
      delivered dose was known accurately. All irradiations were done at dmax in
      polystyrene for both photons and electrons, all films were from the same batch,
      and were developed at the same time. We also exposed the EDR2 films in a solid
      water phantom to produce central axis depth dose curves. These data were compared
      against percent depth dose curves measured in a water phantom using an IC-10 ion
      chamber, Kodak XV2 film, and a PTW electron diode. The response of this film was
      the same for both 6 and 18 MV x rays, but showed an apparent energy-dependent
      enhancement for electron beams. The response of the film also increased with
      increasing electron energy. This caused the percent depth dose curves using film
      to be shifted toward the surface compared to the ion chamber data.

PMID- 14596309
TI  - EGSNRC Monte Carlo study of the effect of photon energy and field margin in
      phantoms simulating small lung lesions.
AB  - The dose distribution in small lung tumors (coin lesions) is affected by the
      combined effects of reduced attenuation of photons and extended range of
      electrons in lung. The increased range of electrons in low-density tissues can
      lead to loss of field flatness and increased penumbra width, especially at high
      energies. The EGSNRC Monte Carlo code, together with DOSXYZNRC, a three
      dimensional voxel dose calculation module has been used to study the
      characteristics of the penumbra in the region of the target-lung interfaces for
      various radiation beam energies, lung densities, target-field edge distances,
      target size, and depth. The Monte Carlo model was validated by film measurements
      made in acrylic (simulating a tumor) imbedded in cork (simulating the lung). Beam
      profiles that are deemed to be acceptable are defined as those in which no point
      within the planning target volume (target volume plus 1 cm margin) received less
      than 95% of the dose prescribed to the center of the target. For parallel opposed
      beams and 2 cm cube target size, 6 MV photons produce superior dose distribution
      with respect to penumbra at the lateral, anterior, and posterior surfaces and
      midplane of the simulated target, with a target-field edge distance of 2.5 cm. A
      lesser target-field edge distance of 2.0 cm is required for 4 MV photons to
      produce acceptable dose distribution. To achieve equivalent dose distribution
      with 10 and 18 MV photons, a target-field edge distance of 3.0 and 3.5 cm,
      respectaively, is required. For a simulated target size of 4 cm cube, a target
      field edge distance of 2, 2.5, and 3 cm is required for 6, 10, and 18 MV photons,
      respectively, to yield acceptable PTV coverage. The effect, which is predominant
      in determining the target dose, depends on the beam energy, target-field edge
      distance, lung density, and the depth and size of the target.

PMID- 14596310
TI  - Performance of a 41 x 41 cm2 amorphous silicon flat panel x-ray detector designed
      for angiographic and R&F imaging applications.
AB  - We measured the physical imaging performance of a 41 x 41 cm2 amorphous silicon
      flat panel detector designed for angiographic and R&F imaging applications using
      methods from the emerging IEC standard for the measurement of detective quantum
      efficiency (DQE) in digital radiographic detectors. Measurements on 12 production
      detectors demonstrate consistent performance. The mean DQE at the detector center
      is about 0.77 at zero frequency and 0.27 at the Nyquist frequency (2.5 cycles/mm)
      when measured with a 7 mm of Al HVL spectrum at about 3.6 microGy. The mean MTF
      at the center of the detector for this spectrum is 0.24 at the Nyquist frequency.
      For radiographic operation all 2048 x 2048 detector elements are read out
      individually. For fluoroscopy, the detector operates in two 30 frame per second
      modes: either the center 1024 x 1024 detector elements are read out or the entire
      detector is read out with 2 x 2 pixel binning. A model was developed to predict
      differences in performance between the modes, and measurements demonstrate
      agreement with the model. Lag was measured using a quasi-equilibrium exposure
      method and was found to be 0.044 in the first frame and less than 0.007 after 1
      s. We demonstrated that it is possible to use the lag data to correct for
      temporal correlation in images when measuring DQE with a fluoroscopic imaging
      technique. Measurements as a function of position on the detector demonstrate a
      high degree of uniformity. We also characterized dependences on spectrum,
      exposure level, and direction. Finally, we measured the DQE of a current state of
      the art image intensifier/CCD system using the same method as for the flat panel.
      We found the image intensifier system to have lower DQE than the flat panel at
      high exposure levels and approximately equivalent DQE at fluoroscopic levels.

PMID- 14596311
TI  - Evaluating radiographic parameters for mobile chest computed radiography:
      phantoms, image quality and effective dose.
AB  - Conventional chest radiography is technically difficult because of wide
      variations in tissue attenuations in the chest and limitations of screen-film
      systems. Mobile chest radiography, performed bedside on hospital inpatients,
      presents additional difficulties due to geometric and equipment limitations
      inherent in mobile x-ray procedures and the severity of illness in the patients.
      Computed radiography (CR) offers a different approach for mobile chest
      radiography by utilizing a photostimulable phosphor. Photostimulable phosphors
      overcome some image quality limitations of mobile chest imaging, particularly
      because of the inherent latitude. Because they are more efficient in absorbing
      lower-energy x-rays than rare-earth intensifying screens, this study evaluated
      changes in kVp for improving mobile chest CR. Three commercially available
      systems were tested, with the goal of implementing the findings clinically.
      Exposure conditions (kVp and grid use) were assessed with two acrylic-and
      aluminum chest phantoms which simulated x-ray attenuation for average-sized and
      large-sized adult chests. These phantoms contained regions representing the
      lungs, heart and subdiaphragm to allow proper CR processing. Signal-to-noise
      ratio (SNR) measurements using different techniques were obtained for acrylic and
      aluminum disks (1.9 cm diameter) superimposed in the lung and heart regions of
      the phantoms, where the disk thicknesses (contrast) were determined from disk
      visibility. Effective doses to the phantoms were also measured for these
      techniques. The results indicated that using an 8:1, 33 lines/cm antiscatter grid
      improved the SNR by 60-300 % compared with nongrid images, depending on phantom
      and region; however, the dose to the phantom also increased by 400-600%. Lowering
      x-ray tube potential from 80 to 60 kVp improved the SNR by 30-40%, with a
      corresponding increase in phantom dose of 40-50%. Increasing the potential from
      80 to 100 kVp reduced both the SNR and the phantom dose by approximately 10%. The
      most promising changes in technique for trial in clinical implementation include
      using an antiscatter grid, especially for large patients, and potentially
      increasing kVp.

PMID- 14596312
TI  - Dependence of fluence errors in dynamic IMRT on leaf-positional errors varying
      with time and leaf number.
AB  - In d-MLC based IMRT, leaves move along a trajectory that lies within a user
      defined tolerance (TOL) about the ideal trajectory specified in a d-MLC sequence
      file. The MLC controller measures leaf positions multiple times per second and
      corrects them if they deviate from ideal positions by a value greater than TOL.
      The magnitude of leaf-positional errors resulting from finite mechanical
      precision depends on the performance of the MLC motors executing leaf motions and
      is generally larger if leaves are forced to move at higher speeds. The maximum
      value of leaf-positional errors can be limited by decreasing TOL. However, due to
      the inherent time delay in the MLC controller, this may not happen at all times.
      Furthermore, decreasing the leaf tolerance results in a larger number of beam
      hold-offs, which, in turn leads, to a longer delivery time and, paradoxically, to
      higher chances of leaf-positional errors (< or = TOL). On the other end, the
      magnitude of leaf-positional errors depends on the complexity of the fluence map
      to be delivered. Recently, it has been shown that it is possible to determine the
      actual distribution of leaf-positional errors either by the imaging of moving MLC
      apertures with a digital imager or by analysis of a MLC log file saved by a MLC
      controller. This leads next to an important question: What is the relation
      between the distribution of leaf-positional errors and fluence errors. In this
      work, we introduce an analytical method to determine this relation in dynamic
      IMRT delivery. We model MLC errors as Random-Leaf Positional (RLP) errors
      described by a truncated normal distribution defined by two characteristic
      parameters: a standard deviation sigma and a cut-off value deltax0 (deltaxo
      approximately TOL). We quantify fluence errors for two cases: (i) deltax0 >>
      sigma (unrestricted normal distribution) and (ii) deltax0 << sigma (deltax0-
      limited normal distribution). We show that an average fluence error of an IMRT
      field is proportional to (i) sigma/ALPO and (ii) deltax0/ALPO, respectively,
      where ALPO is an Average Leaf Pair Opening (the concept of ALPO was previously
      introduced by us in Med. Phys. 28, 2220-2226 (2001). Therefore, dose errors
      associated with RLP errors are larger for fields requiring small leaf gaps. For
      an N-field IMRT plan, we demonstrate that the total fluence error (if we neglect
      inhomogeneities and scatter) is proportional to 1/square root of N, where N is
      the number of fields, which slightly reduces the impact of RLP errors of
      individual fields on the total fluence error. We tested and applied the
      analytical apparatus in the context of commercial inverse treatment planning
      systems used in our clinics (Helios and BrainScan). We determined the actual
      distribution of leaf-positional errors by studying MLC controller (Varian Mark II
      and Brainlab Novalis MLCs) log files created by the controller after each field
      delivery. The analytically derived relationship between fluence error and RLP
      errors was confirmed by numerical simulations. The equivalence of relative
      fluence error to relative dose error was verified by a direct dose calculation.
      We also experimentally verified the truthfulness of fluences derived from the log
      file data by comparing them to film data.

PMID- 14596313
TI  - Automatic registration of the prostate for computed-tomography-guided
      radiotherapy.
AB  - The recent development of integrated computed tomography (CT)/linear accelerator
      (LINAC) combinations, where the CT scanner and the LINAC use the same patient
      couch, and of kilovoltage cone-beam CT systems attached to the LINAC gantry,
      means that suitable hardware is now available for CT-guided localization of the
      prostate. Clinical implementation is, however, currently impeded by the lack of
      robust and accurate software tools to compare the position of the prostate in the
      CT images used for the treatment plan with its position in the daily CT images.
      Manual registration of the planning CT images with the daily CT images can be
      slow and can introduce significant inter-user variations. We have developed an
      automatic registration technique that is not adversely influenced by changes in
      prostate shape, size or orientation, presence of rectal gas, or bladder filling.
      The cost function used in the registration is the mean absolute difference in CT
      numbers voxel-by-voxel between the daily CT image and the planning CT image for a
      volume extracted from the planning CT images using the original physician-drawn
      gross tumor volume contours. To enhance soft tissue contrast in the prostate
      region and to reduce the impact of rectal gas calcifications and bone on the
      registration, voxels with CT numbers that represent gas or bone are filtered out
      from the calculation. The results of the automatic registration agreed with the
      mean results of seven human observers, with standard deviations of 0.5 mm, 0.5
      mm, and 1.0 mm in the left/right (RL), anterior/posterior (AP), and
      superior/inferior (SI) directions, respectively, for a patient that was
      relatively easy to localize. Agreement (one standard deviation) for a patient
      that was difficult to localize was 0.6 mm, 1.4 mm, and 1.9 mm in the RL, AP, and
      SI directions, respectively. These results are better than the interuser
      uncertainties reported for a manual alignment technique and are close to the
      reported intrauser uncertainties. The results are independent of the shape of
      contours in the original treatment plan, reducing the impact of interobserver
      variations in contouring the prostate. The algorithm is fast and reliable,
      allowing the entire CT localization process to take place in 5-9 minutes. In 120
      CT image sets from seven patients, the failure rate was found to be less than 1%.
      The use of this algorithm will facilitate the clinical implementation of CT
      guided localization of the prostate.

PMID- 14596314
TI  - X-ray micro-CT with a displaced detector array: application to helical cone-beam
      reconstruction.
AB  - In x-ray micro-CT applications, it is useful to increase the field of view by
      offsetting a two-dimensional (2D) detector array. In this technical note, we
      briefly review the methods for image reconstruction with an asymmetric 2D
      detector array, elaborate on the use of an associated weighting scheme in the
      case of helical/spiral cone-beam scanning, and perform a series of numerical
      tests to demonstrate helical cone-beam image reconstruction with such an
      arrangement.

PMID- 14596315
TI  - Quality assurance for computed-tomography simulators and the computed-tomography
      simulation process: report of the AAPM Radiation Therapy Committee Task Group No.
      66.
AB  - This document presents recommendations of the American Association of Physicists
      in Medicine (AAPM) for quality assurance of computed-tomography- (CT) simulators
      and CT-simulation process. This report was prepared by Task Group No. 66 of the
      AAPM Radiation Therapy Committee. It was approved by the Radiation Therapy
      Committee and by the AAPM Science Council.

PMID- 14596316
TI  - Improving the resolution of dynamic intensity modulated radiation therapy
      delivery by reducing the multileaf collimator sampling distance.
AB  - The conformality of a dose distribution delivered by a multileaf collimator (MLC)
      for intensity modulated radiation therapy (IMRT) is limited in the direction
      perpendicular to leaf motion by the finite leaf width. Two methods of improving
      the resolution of IMRT intensity maps in this direction were investigated. In the
      first, the desired fluence distribution is considered to be sampled by the MLC,
      with the sampling distance being the center-to-center distance between the MLC
      leaves. The sampling distance is reduced below the leaf width by combining
      separate irradiations with a couch shift between them. This has been applied to
      static field therapy [Galvin et al., Int. J. Radiat. Oncol., Biol., Phys. 35, 89
      94 (1996)], and was proposed for IMRT by Bortfeld et al. [Med. Phys. 27, 2494
      2502 (2000)]. In the second method, two MLC component fluences, with leaf width L
      = 2deltay and offset by deltay, are combined to reproduce desired intensity bins
      with deltay width. The effect of MLC leaf sampling distance on dose resolution
      was quantified for both 1.0 and 0.5 cm MLC leaf widths, utilizing a high
      resolution bar-pattern fluence, an annular shaped fluence, and an intensity step
      edge. Improvement in resolution was found for the 1.0 cm leaf width at a sampling
      distance of 0.5 cm, with only a small benefit for further reduction. For the 0.5
      cm leaf width, a sampling distance of 0.25 cm resulted in a dose resolution that
      was nearly independent of direction.

PMID- 14596317
TI  - General surface reconstruction for cone-beam multislice spiral computed
      tomography.
AB  - A new family of cone-beam reconstruction algorithm, the General Surface
      Reconstruction (GSR), is proposed and formulated in this paper for multislice
      spiral computed tomography (CT) reconstructions. It provides a general framework
      to allow the reconstruction of planar or nonplanar surfaces on a set of rebinned
      short-scan parallel beam projection data. An iterative surface formation method
      is proposed as an example to show the possibility to form nonplanar
      reconstruction surfaces to minimize the adverse effect between the collected cone
      beam projection data and the reconstruction surfaces. The improvement in accuracy
      of the nonplanar surfaces over planar surfaces in the two-dimensional approximate
      cone-beam reconstructions is mathematically proved and demonstrated using
      numerical simulations. The proposed GSR algorithm is evaluated by the computer
      simulation of cone-beam spiral scanning geometry and various mathematical
      phantoms. The results demonstrate that the GSR algorithm generates much better
      image quality compared to conventional multislice reconstruction algorithms. For
      a table speed up to 100 mm per rotation, GSR demonstrates good image quality for
      both the low-contrast ball phantom and thorax phantom. All other performance
      parameters are comparable to the single-slice 180 degrees LI (linear
      interpolation) algorithm, which is considered the "gold standard." GSR also
      achieves high computing efficiency and good temporal resolution, making it an
      attractive alternative for the reconstruction of next generation multislice
      spiral CT data.

PMID- 14596318
TI  - Adapting inverse planning to patient and organ geometrical variation: algorithm
      and implementation.
AB  - Image guided radiotherapy has the potential to improve both tumour control and
      normal tissue sparing by including temporal patient specific geometry information
      into the adaptive planning process. In this study we present a practical method
      of image guided adaptive inverse planning based on computed tomography (CT) and
      portal image feedback during the treatment course. The method is based on a
      general description of the radiotherapy optimization problem subject to dynamic
      geometrical variations of the patient/organs. We will demonstrate the feasibility
      of off-line image feedback into the inverse planning process with the example of
      three prostate cancer patients. CT and portal images acquired during the early
      course of the treatment are used to predict the geometrical variation
      distribution of a patient and to re-optimize the treatment plan accordingly. We
      will study the convergence of the optimization problem with respect to the number
      of image measurements and adaptive feedback loops.

PMID- 14596319
TI  - Comparison of alpha/beta estimates from homogeneous (individual) and
      heterogeneous (population) tumor control models for early stage prostate cancer.
AB  - Radiobiological parameter estimates for prostate cancer are obtained from both a
      homogeneous (individual) and heterogeneous (population) tumor control model based
      on Poisson statistics and the linear quadratic model of cell survival. Parameter
      estimates for both models are highly correlated: statistically equivalent fits
      are achievable using either (1) linear quadratic (LQ) parameters with low numbers
      of radioresistant tumor stem cells, or (2) LQ parameters with corresponding
      larger number of radiosensitive tumor stem cells. A theoretical framework is
      developed to explain this correlation. A Monte Carlo error analysis based on
      binomial statistics is used to estimate confidence intervals for all parameter
      estimates. It was found that both the homogeneous and heterogeneous models
      produce approximately equivalent estimates of radiobiological parameters,
      including the alpha/beta ratio. However, the 95% confidence interval for the
      alpha/beta ratio derived from the heterogeneous model are considerably larger
      than those derived from the homogeneous model, which indicate the homogeneous
      model overestimates the statistical significance of the alpha/beta estimate.

PMID- 14596320
TI  - Contamination dose from photoneutron processes in bodily tissues during
      therapeutic radiation delivery.
AB  - Dose to the total body from induced radiation resulting from primary exposure to
      radiotherapeutic beams is not detailed in routine treatment planning though this
      information is potentially important for better estimates of health risks
      including secondary cancers. This information can also allow better management of
      patient treatment logistics, suggesting better timing, sequencing, and conduct of
      treatment. Monte Carlo simulations capable of taking into account all
      interactions contributing to the dose to the total body, including neutron
      scattering and induced radioactivity, provide the most versatile and accurate
      tool for investigating these effects. MCNPX code version 2.2.6 with full IAEA
      library of photoneutron cross sections is particularly suited to trace not only
      photoneutrons but also protons and heavy ion particles that result from
      photoneutron interactions. Specifically, the MCNPX code is applied here to the
      problem of dose calculations in traditional (non-IMRT) photon beam therapy.
      Points of calculation are located in the head, where the primary irradiation has
      been directed, but also in the superior portion of the torso of the ORNL
      Mathematical Human Phantom. We calculated dose contributions from neutrons,
      protons, deutrons, tritons and He-3 that are produced at the time of photoneutron
      interactions in the body and that would not have been accounted for by
      conventional radiation oncology dosimetry.

PMID- 14596321
TI  - Elemental maps in human allantochorial placental vessels cells: 2. MgCl2 and
      MgSO4 effects.
AB  - Extracellular magnesium salts are known to interfere with ionic channels in the
      cellular membranes. The membrane potential, a regulator of vascular tone, is a
      function of the physiological activities of ionic channels (particularly, K+ and
      Ca2+ channels in these cells). These channels regulate the ionic distribution
      into these cells. Micro-Particule Induced X-ray Emission (PIXE) analysis was
      applied to determine the ionic composition of vascular smooth muscle cells (VSMC)
      and of vascular endothelial cells (VEC) in the placental human allantochorial
      vessels in a physiological medium (Hanks' solution) modified by the addition of 2
      mM MgCl2 or 2 mM MgSO4 which block the calcium-sensitive K+ channels (K(Ca)), the
      ATP-sensitive K+ channels (K(ATP)) and the voltage-sensitive K+ (K(df)) and Ca2+
      channels. In VSMC (media layer), the addition of MgCl2 induced no modification of
      the K, Cl, P, S and Ca concentrations but increased the Na and Mg concentrations
      and the addition of MgSO4 only significantly increased the Mg concentration, the
      other ion concentrations remaining constant. In endothelium (VEC), MgCl2 or MgSO4
      addition implicated the same observations as in VSMC. These results confirmed the
      blockage of K(df), K(Ca), K(ATP) and Ca channels in VSMC and VEC by magnesium
      salts, the relationship between Mg2+ ions and internal Na and demonstrated the
      possible intervention of a Na+/Mg2+ exchanger.

PMID- 14596322
TI  - Effect of gamma irradiation on magnesium content in rat tissues.
AB  - Studies in the field of radiation chemistry have shown that the greatest damage
      induced by ionizing radiation appears as a consequence of uncontrolled production
      of free radicals in the living organism, which have their origin in oxidative
      stress induced by ionizing radiation. Ionizing radiation also has an influence on
      the content of bio-essential elements in mammalian tissues. Analysis of the
      concentration of magnesium (Mg) seven days after whole body irradiation with a
      single dose of 4.2 Gy of gamma rays from a 60Co source, showed a slight reduction
      in Mg content in the following analyzed tissues: front brain (cerebral
      hemispheres with underlying structures except pituitary gland and hypothalamus)
      and adrenal glands from irradiated animals as compared to the non-irradiated
      controls, this difference however being not statistically significant. No
      significant differences in the content of Mg were detected in the pituitary
      glands between the two groups of animals. In contrast, a significantly higher
      concentration of Mg seven days after irradiation was measured in the hind brain
      containing cerebellum with lateral lobes and flocculi (p < 0.005), hypothalamus
      (p < 0.0001) and testes (p < 0.05) of irradiated animals, when compared to the
      non-irradiated controls. This accumulation of Mg, in particular tissues of the
      Central Nervous System (CNS) and endocrine glands regulated by the pituitary
      gland and hypothalamus, may indicate the differential role Mg++ ions have in
      keeping the homeostasis of certain tissues, those of the brain, adrenal glands
      and testes after exposure to ionizing radiation.

PMID- 14596323
TI  - Mg citrate found more bioavailable than other Mg preparations in a randomised,
      double-blind study.
AB  - Published data on the bioavailability of various Mg preparations is too
      fragmented and scanty to inform proper choice of Mg preparation for clinical
      studies. In this study, the relative bioavailability of three preparations of Mg
      (amino-acid chelate, citrate and oxide) were compared at a daily dose of 300 mg
      of elemental Mg in 46 healthy individuals. The study was a randomised, double
      blind, placebo-controlled, parallel intervention, of 60 days duration. Urine,
      blood and saliva samples were taken at baseline, 24 h after the first Mg
      supplement was taken ('acute' supplementation) and after 60 days of daily Mg
      consumption ('chronic' supplementation). Results showed that supplementation of
      the organic forms of Mg (citrate and amino-acid chelate) showed greater
      absorption (P = 0.033) at 60 days than MgO, as assessed by the 24-h urinary Mg
      excretion. Mg citrate led to the greatest mean serum Mg concentration compared
      with other treatments following both acute (P = 0.026) and chronic (P = 0.006)
      supplementation. Furthermore, although mean erythrocyte Mg concentration showed
      no differences among groups, chronic Mg citrate supplementation resulted in the
      greatest (P = 0.027) mean salivary Mg concentration compared with all other
      treatments. Mg oxide supplementation resulted in no differences compared to
      placebo. We conclude that a daily supplementation with Mg citrate shows superior
      bioavailability after 60 days of treatment when compared with other treatments
      studied.

PMID- 14596324
TI  - Is magnesium a marker of disordered mineral metabolism in males with idiopathic
      recurrent calcium urolithiasis? Observations focussing on fasting magnesiuria and
      magnesiemia, protein and other substances in urine and plasma.
AB  - Mg can theoretically play a role in renal calcium stone formation of IRCU
      patients, but the status of Mg is uncertain. The aim of this study was to
      investigate whether in IRCU variation of Mg in fasting urine and plasma is
      associated with altered urine Ca, Pi, oxalate, Ca/Pi ratio, supersaturation and
      other factors, the clinical severity of stone disease (metabolic activity; MA)
      included. This was a cross-sectional study (284 IRCU patients), comprising males
      with mean age in the fifth decade and unimpaired renal function. Patients had an
      unrestricted home diet, standardized laboratory procedures, including sample
      collection (daily and fasting urine, plasma), with classification of patients
      according to tertiles of fasting Mg-uria, keeping comparable age, the number of
      patients with renal stones present or absent, and normo- or idiopathic
      hypercalciuria. MA was scored. We found that the tertile I patients (= referent)
      exhibited sub-normal fasting Mg excretion (< 4 mg/2 h) and fractional excretion
      (< 3.5%), in daily urine the lowest Mg and oxalate, but highest Ca excretion
      rate; compared with tertile III, tertile I patients had significantly lower
      plasma total (not ultrafiltrable) Mg, blood bicarbonate and pH, and the lowest
      MA; fasting urinary excretion of Ca and citrate were also low, but urinary Pi,
      body weight, plasma glucose and insulin were increased. In tertile III not only
      was Mg-uria (excretion, FE) significantly elevated vs I, but so were urinary pH,
      excretion of sodium, Ca, potassium, protein (total and non-albumin) and citrate,
      FE sodium and Ca, the urinary molar ratios Ca/Pi and Mg/Potassium, hydroxyapatite
      supersaturation, bone resorption markers, and MA; in this environment urinary
      oxalate and Ca oxalate supersaturation were unchanged, plasma glucose, insulin
      and parathyroid hormone decreased. The tertile II patients, showing intermediate
      Mg excretion, also exhibited (vs. I) increase of FE Mg, urinary excretion and FE
      of sodium and Ca, excretion of protein, citrate and bone markers, the ratios
      Ca/Pi and Mg/Potassium, and MA. When urinary Ca/Pi was considered as the outcome
      of disordered metabolism, significant determinants (according to multiple
      regression analysis) were urinary Pi (negative), Ca and Mg/Potassium (positive);
      significant determinants of MA, the sum of stone-forming processes, were the
      urinary concentration of non-albumin protein, Mg/Potassium and sodium (all
      positive). Among IRCU patients 1) approx. one third is in need of Mg conservation
      by the kidney, associated with low plasma total Mg, modest metabolic acidosis, a
      trend towards overweight, high plasma insulin and glucose; 2) low Mg- or acidosis
      induced increase of bone resorption may follow, attenuating glycemia and
      insulinemia but forcing the kidney to functional adaptation, manifesting as a
      rise of urinary sodium, Mg, Ca, Pi, Ca/Pi, pH and protein, together presumably
      aggravating MA; 3) larger controlled studies are justified, to decide whether Mg
      deficiency initiates renal Ca stones, and if urinary Mg loss exaggerates IRCU.

PMID- 14596325
TI  - Intralymphocyte magnesium decrease in patients with primary aldosteronism.
      Possible links with cardiac remodelling.
AB  - Our group have described a group of patients with primary aldosteronism which is
      characterized by significantly decreased intralymphocyte ionized magnesium
      concentration. Some models of experimental hyperaldosteronism are characterized
      by cardiovascular fibrosis but despite this fact the link between a negative
      magnesium balance and fibrosis is lacking. Consequently, to shed some light on
      the relationships between magnesium and tissue fibrosis we tested the in vitro
      effects of incubating human fibroblasts in low magnesium medium on mRNA collagen
      I and III gene expression by northern blot analysis. Both collagen I and III mRNA
      gene expression were increased by magnesium deprivation. The increase in collagen
      expression was similar for both collagen I and III. These data are in favour of a
      potential link between magnesium homeostasis and collagen synthesis. A
      physiopathologic mechanism linking magnesium homeostasis to the state of collagen
      turnover may have important clinical correlates such as cardiac remodelling in
      congestive heart failure.

PMID- 14596326
TI  - Importance of magnesium ions in the mechanism of catalysis by a hammerhead
      ribozyme: strictly linear relationship between the ribozyme activity and the
      concentration of magnesium ions.
AB  - Analysis, based on kinetic solvent isotope effects, demonstrated that no proton
      transfer occurs in reactions catalyzed by a 32-mer hammerhead ribozyme (R32) in
      the presence of magnesium ions, whereas proton transfer occurs in reactions
      catalyzed by R32 in the presence of high concentrations of monovalent NH4+ ions
      without metal ions, demonstrating that the detailed mechanism of action of the
      hammerhead ribozyme might change depending on the environment. Importantly, when
      the concentration of magnesium ions was gradually increased from 1 mM to up to
      800 mM, the R32 ribozyme activity increased linearly without reaching a plateau
      value. This phenomenon can be explained by a model in which a catalytic magnesium
      ion with a very low affinity (dissociation constant, Kd > 800 mM) exists and/or
      the predominant inactive complex converts to a minor active complex before the
      cleavage reaction.

PMID- 14596327
TI  - Beta-2 mimetics and magnesium: true or false friends?
AB  - Physiological beta stimulation may be involved in the regulation of magnesium
      status namely by homeostatic increase of magnesemia during magnesium deficiency.
      But conversely excessive beta stimulation namely by use of pharmacological high
      doses of beta mimetics may induce a decrease of magnesemia. Two different types
      of magnesium therapy ought to be distinguished. Nutritional magnesium therapy
      which may physiologically palliate a magnesium deficiency due to an insufficient
      magnesium intake. It is devoid of any toxicity. Pharmacological magnesium
      therapy, whatever the magnesium status, causes a iatrogenic magnesium load. It
      may induce magnesium toxicity. Tocolysis is the one common obstetrical indication
      for beta mimetics and magnesium. Beta-2 mimetics are the reference tocolytic
      drugs in most countries. But high doses of beta-2 mimetics for suppression of
      premature labor are associated to a high incidence of maternal, fetal and
      neonatal side effects. Tocolysis must then be discontinued or limited to shorter
      treatments with the lowest possible doses. Nutritional magnesium therapy which
      palliates gestational magnesium deficiency is efficient and atoxic. Conversely,
      high doses of intravenous MgSO4 for tocolysis are less efficient and unsafe.
      Because of its maternal and above all pediatric side effects, this maternal
      pharmacological magnesium therapy should be abandoned for tocolysis.
      Investigation of the therapeutic ratio of various magnesium salts before their
      clinical use could help to determine if other anions different from sulfate could
      decrease the toxicity. Beta-2 agonists are first line asthma therapy, but their
      safety is debated. Asthma and Chronic Obstructive Pulmonary Disease (COPD) per se
      may induce magnesium depletion related to a dysregulation of the control
      mechanisms of magnesium status. It requires a correction of its causal
      regulation, but nutritional magnesium supplementation is ineffective. When
      chronic primary magnesium deficiency coexists with obstructive bronchial
      disorders, it constitutes a decompensatory factor. Atoxic nutritional magnesium
      therapy may palliate this coexistent magnesium deficiency. Pharmacological
      magnesium treatment for obstructive pulmonary diseases is not very efficient with
      low safety. Combination of palliating nutritional magnesium therapy and of beta-2
      mimetics for tocolysis or pulmonary obstructive indications may be beneficial and
      remain atoxic. Conversely combination of intravenous tocolytic high doses of
      magnesium and of beta-2 mimetics is contra-indicated because of its dubious
      efficiency and its possible toxicity. The possible role of SO4- as regards
      toxicity must be discussed. Contra-indications of lower intravenous or inhaled Mg
      doses for pulmonary bronchial obstruction are less imperative than for tocolysis.
      The selection of a particular magnesium salt among others should take into
      account reliable plasmacological and toxicological data. It seems necessary to
      determine the therapeutic ratio (LD50/ED50) of the various available magnesium
      salts before pharmacological use.

PMID- 14596328
TI  - Automatic pre-segmentation of running speech improves the robustness of several
      acoustic voice measures.
AB  - In order to study vocal loading, we developed a speech analysis environment for
      continuous speech. The objective was to build a robust system capable of handling
      large amounts of data while minimizing the amount of user-intervention required.
      The current version of the system can analyze up to five-minute recordings of
      speech at a time. Through a semiautomatic process it will classify a speech
      signal into segments of silence, voiced speech and unvoiced speech. Parameters
      extracted from the input signal include fundamental frequency, sound pressure
      level, alpha-ratio and speech segment information such as the ratio of speech to
      silence. This paper presents results from the performance evaluation of the
      system, which shows that the analysis environment is able to perform robust and
      consistent measurements of continuous speech.

PMID- 14596329
TI  - The visual sort and rate method for perceptual evaluation in listening tests.
AB  - This paper introduces the Visual Sort and Rate (VSR) method which can be utilized
      for perceptual rating of sound stimuli. The method facilitates comparing similar
      stimuli, thus making the rank ordering of the stimuli easier. To examine the
      potential benefits of the method, it was compared with two other methods for
      perceptual rating of audio stimuli. The first method was a straightforward
      computer-based implementation of a visual analogue scale (VAS) allowing multiple
      playbacks and re-play of previously heard stimuli (C-VAS). The second method
      utilized a VAS where the responses were given on paper (P-VAS). The three methods
      were compared by using two sets of stimuli. The first set was a synthetically
      generated series of stimuli mimicking the vowel /a/ with different spectral
      tilts. In this test, a single parameter was rated. The second set of stimuli was
      a naturally spoken voice. For this set of stimuli three parameters were rated.
      Results show that the VSR method gave better reliability of the subjects' ratings
      in the single-parameter tests: Pearson and Spearman correlation coefficients were
      significantly higher for the VSR method than for the other methods. For the multi
      parameter, intra-subject test, significantly higher Pearson correlation
      coefficients were found for the VSR method than for the VAS on paper.

PMID- 14596330
TI  - Voice disorders in children with oral motor dysfunction: perceptual evaluation
      pre and post oral motor therapy.
AB  - A few clinical investigations of children's voices have suggested a relation
      between voice deviation and oral motor and sensory dysfunction. This motivated
      the present retrospective study of the occurrence of voice disorders in a group
      of children with oral motor problems. A further aim was to evaluate the effect of
      an oral motor and articulatory treatment programme upon voice function in this
      patient group. Subjects were 38 children with oral motor deficits who had
      received and finished therapy at the clinic. The recordings of a picture naming
      task, before onset of therapy and at therapy ending, were selected. The voices
      were presented in random order on a test tape and perceptually evaluated by an
      expert panel of speech pathologists. Eleven perceptual parameters were selected,
      based on previous investigations of children's voices. Ten of these parameters
      were represented by a 100 mm visual analogue scale. Register was represented by a
      categorical scale with the options chest, falsetto, and child voice register. The
      results were compared with previous investigations of child voice function.
      Results indicated: 1) The occurrence of voice disorders in the present group of
      children with oral motor difficulties was somewhat lower than in children with
      normal articulation. 2) Oral motor treatment also influenced and improved the
      perceptual impression of voice quality in this group.

PMID- 14596331
TI  - Vocal hygiene in radio students and in radio professionals.
AB  - In this study 27 future professional voice users (i.e., radio students) and 53
      professional voice users (i.e., radio professionals) were questioned on their
      vocal hygiene. Both groups differed clearly in age and in radio experience. The
      mean age of the radio students was 22 years, whereas the mean age of the radio
      professionals was 41 years; radio students had no radio experience and radio
      professionals' experience ranged from 2 to 32 years. This study shows that the
      vocal hygiene of radio professionals is not superior to the vocal hygiene of
      radio students. On the contrary, every group has a distinctive vocal hygiene
      profile. The intake of coffee was significantly higher in radio professionals (p
      < 0.001) and they indicated significantly more vocal fatigue (p = 0.028). The
      radio students, on the other hand, experienced more acid reflux problems (p <
      0.001) and signalled significantly more hoarseness (p = 0.012). Next to this,
      both groups smoked more than one could expect from (future) professional voice
      users (radio students: 33%; radio professionals: 28%). This study demonstrates
      the necessity of an adapted vocal hygiene education programme for both future and
      professional voice users, as they seem to underestimate the negative implications
      of bad vocal hygiene.

PMID- 14596332
TI  - High-speed imaging: applications and development.
AB  - This article shows some examples of applications of digital high-speed imaging in
      phoniatrics. Advantages and disadvantages of digital high-speed imaging as
      compared to the current world-wide standard, videostroboscopy, are discussed as
      well as possible future developments in this area. Parts of this paper were
      presented by the authors at the Pan European Voice Conference in Stockholm in
      2001 (Pevoc IV).

PMID- 14596333
TI  - Dr. Daniel W. Armstrong.

PMID- 14596334
TI  - Determination of aristolochic acids by capillary electrophoresis.
AB  - A method for the separation and quantification of aristolochic acids by capillary
      electrophoresis is described. Buffer solutions composed of sodium dihydrogen
      phosphate, sodium borate, and sodium dodecyl sulfate at pH 6.5-7 were found to be
      suitable for the separation of aristolochic acids, which can be well resolved in
      a few minutes. The separation and identification of six aristolochic acids
      contained in a commercial tincture called charrua, a traditional herbal medicine
      consisting of a hydroalcoholic extract of Aristolochia argentina, corroborate the
      usefulness of the method. The eventual toxic properties of the aristolochic acid
      containing charrua tincture are discussed.

PMID- 14596335
TI  - Capillary electrophoresis as an orthogonal technique in HPLC method validation.
AB  - High-performance liquid chromatography is usually used to assay the main compound
      and organic impurity content of drug substance and drug product during
      pharmaceutical development. A crucial validation parameter of these methods is
      specificity--the ability to unequivocally assess the analyte in the presence of
      component expected to be present. Typically, these include impurities,
      degradation products, and matrices. Besides adequate chromatographic separation
      with sufficient selectivity, additional 2- or 3-D spectroscopic or
      chromatographic tools are frequently necessary for this purpose. In our current
      practice, HPLC is used with ultraviolet photodiode array detection and on-line
      mass spectrometry (LC-UVDAD-MS) during the assessment of specificity. Although
      this approach is very powerful and can solve the majority of problems, separation
      of isomers of the main compound is still difficult. Since HPLC usually cannot
      offer the required selectivity and because of the similar molecular weights,
      structural isomers are not specifically detected using LC-MS. Capillary
      electrophoresis, on the other hand, offers high separation efficiency and can be
      applied as an adjunct to HPLC. Therefore, a set of highly selective CE methods is
      used orthogonally in the specificity assessment of HPLC methods.

PMID- 14596336
TI  - Optimized separation conditions of soy isoflavonoids in urine by capillary zone
      electrophoresis.
AB  - The last few years have seen a growing interest in the study of the sources and
      metabolism of isoflavones due to their potential role in the prevention and
      treatment of chronic disease (i.e., coronary artery disease, osteoporosis, and
      certain types of cancer). Furthermore, isoflavonoids have reportedly been
      instrumental in relieving menopausal symptoms (i.e., hot flashes, night sweats,
      other vasomotor symptoms, and bone loss). Isoflavonoids are compounds that occur
      naturally in plants and belong to the phytoestrogen family, as do coumestans and
      lignans. There is much to learn about the effects of isoflavonoids and their
      potential health benefits; thus they are researched extensively through
      molecular, preclinical, and clinical studies. Capillary zone electrophoresis
      (CZE) was explored as a new tool for characterizing the content of isoflavonoids
      in the urine of subjects who consume large amounts of soy and derivative
      products. The effect of pH, buffer concentration, and instrument parameters on
      the migration behavior of these products was studied. Due to the phenolic nature
      of isoflavonoids, alkaline pHs (8.20-9.90) were tested. The influence of
      electrolyte concentration in the 50-250 mM range on migration times and
      resolution was researched. Solid-phase extraction (SPE) was carried out for
      sample cleanup and preconcentration.

PMID- 14596337
TI  - Capillary electrophoresis analysis of histones, histone variants, and their post
      translationally modified forms: a review.
AB  - Histones are the most intensively studied group of basic nuclear proteins and are
      of great importance with regard to the organization of chromatin structure and
      control of gene activity. The complexity of this protein family places very high
      demands on the analytical methods applied. The advent of high-performance
      capillary electrophoresis provided a promising new tool for their separation,
      which is an essential prerequisite for studying the biological role of this
      protein family. Problems inherent to histone analysis due to their unique
      physical and chemical properties are reviewed, and the pros and cons of distinct
      strategies developed for CE separation of these proteins are discussed.

PMID- 14596338
TI  - The potential use of fiber optics for detection in microchip separation and
      miniaturized flow-cell systems.
AB  - This article evaluates the potential of using fiber optics as a detection tool
      during electrophoretic separations or identification and quantification of
      analytes in miniaturized systems, including microchips. This paper covers reports
      in the literature from 1989 to June 2002. The articles have been chosen based on
      various aspects of the instrumentation including the microchip substrates,
      channel size and geometry, pathlength, fiber and detector types, light source,
      separation conditions, detection limits, and applications-all with the goal of
      comparing and contrasting optical detections. This review has been divided into
      three groups: fluorescence measurement-based studies, absorbance measurement
      based studies, and innovative studies in chronological order.

PMID- 14596339
TI  - High-throughput genotyping by microchip electrophoresis.
AB  - Easy applicability of modern microfabrication technology to electrophoresis
      microchips has initiated a rapidly moving interdisciplinary field in analytical
      chemistry. Electric field-mediated separations in microfabricated devices are
      significantly faster than conventional electrophoresis methods and are usually
      completed in seconds to minutes. The flexibility of fluidic manipulations in
      electrophoresis microchips allows the use of a variety of separation techniques
      and conditions. In this study, large-scale genotyping of the repeat polymorphism
      in the regulatory (promoter) region of the serotonin transporter gene 5-HTT
      linked polymorphic region (5-HTTLPR) was attempted using polymerase chain
      reaction (PCR) amplification followed by rapid microchip electrophoresis analysis
      of the amplicons.

PMID- 14596340
TI  - Determination of beta-hydroxyacyl CoA-dehydrogenase activity in meat by
      electrophoretically mediated microanalysis.
AB  - The combined use of an in-tube enzyme assay and capillary electrophoresis for
      determining beta-hydroxyacyl CoA-dehydrogenase (beta-HADH) activity in meat was
      investigated. Beta-HADH is a significant mitochondrial enzyme in food muscle;
      thus, the determination of its activity is important in food analysis. The
      enzymatic assay and the separation of the reaction products were carried out by
      electrophoretically mediated microanalysis (EMMA) using a plug-plug reaction mode
      at variable potential. For the quantification of beta-HADH activity, the rate of
      conversion of reduced beta-nicotinamide adenine dinucleotide (NADH) to beta
      nicotinamide adenine dinucleotide (NAD+) was calculated by determining NAD+ at
      260 nm. A calibration curve for NAD+ concentration versus normalized areas showed
      a highly significant (p < 0.001) linear relationship (R2 = 0.993). Accurate
      quantification of beta-HADH activity was achieved since on-line monitoring
      allowed us to account for the NAD+ produced from NADH degradation by applying a
      correction factor. An average reaction time of 0.66 +/- 0.06 sec was determined
      for a protein concentration in the range of 0.1-0.5 mg protein/mL. The assay was
      reproducible since coefficients of variation of less than 6.2% were calculated
      for triplicate analyses.

PMID- 14596341
TI  - Evaluation of the immune response to hepatitis B vaccination in children aged 1-3
      years in Malatya, Turkey.
AB  - By the end of 1998, Turkey had launched the routine vaccination of infants
      against hepatitis B. The purpose of the study is to evaluate the immune response
      in a sample of vaccinated children aged 1-3 years in the city of Malatya. A total
      of 210 vaccinated children 12 to 48 months old were selected for the study with
      30 cluster sampling in the city of Malatya, Turkey. The children were visited at
      their homes during January-April 2002. The information on demographic
      characteristics, family's and child's medical history was gathered, childrens'
      weight and height were measured and blood samples were taken. Anti-HBs, HbsAg and
      anti-HBc titers were assayed by micro-ELIZA from the sera. The mean age of the
      children was 26.3 months, 100 (47.6%) were male and 110 (52.4%) were female.
      Overall, 203 (96.7%) children had protective anti-HBs levels (> or = 10 IU/l),
      0.5% showed evidence of natural infection (with positive anti-HBc and anti-HBs
      titers), 0.5% had acute or chronic infection (with positive HbsAg and anti-HBc
      titers) and 2.3% were seronegative. Geometric mean titer of anti-HBs among
      vaccinated children except those who had positive anti-HBc titers was 138.7
      mIU/ml (95% CI:124.7-154.2) and seroconversion rates did not differ by age, sex,
      anthropometric measurements, time after third dose and place of vaccine
      administered (P > 0.05). The high seroprotection rate over 95% showed that
      routine infant vaccination program for hepatitis B was successfully carried out
      in the city Malatya.

PMID- 14596342
TI  - Helicobacter pylori infection in patients with Hepatitis C Virus positive chronic
      liver diseases.
AB  - BACKGROUND AND GOALS: One-third of patients with liver cirrhosis suffers from
      acute peptic ulcer, a disease strongly correlated with Helicobacter pylori (H.
      pylori) infection. We report the seroprevalence of antibodies to H. pylori in 179
      patients with Hepatitis C Virus (HCV)-related chronic active hepatitis and
      cirrhosis. MATERIALS AND METHODS: Among patients, 135 (86 males and 49 females,
      mean age 51.2 +/- 13.28, range 27-77 years) had chronic active hepatitis (CAH)
      and 44 cirrhosis (28 males and 16 females, mean age 62.4 +/- 9.2, range 37-77
      years). Serum antibodies to H. pylori were tested using a commercial enzyme
      immunosorbent assay. The control population consisted of 619 consecutive blood
      donors (523 males, 96 females, mean age 47 +/- 5.3 years, range 18-65). RESULTS:
      The overall prevalence of antibodies to H. pylori was 73.1% (131/179) among
      patients and 47% (291/619) among blood donors (p<0.0001; OR 3.08 [95%CI, 2.10
      4.51]). 70.5% (24/34) of patients aged less than 40 years were seropositive for
      H. pylori versus 34.2% (90/263) of controls (p<0.0001; OR 4.61[95%CI, 2.0
      10.85]). Among cirrhosis patients, the prevalence of antibodies to H. pylori was
      79.5% (35/44) versus 47% (291/619) of controls (p<0.0001; OR 4.38 [95%CI, 1.98
      9.98]). Overall seroprevalence among CAH patients was 71.1% (96/135) versus 47%
      (291/619) of blood donors (p<0.0001; OR 2.77 [95%CI, 1.82-4.24]). CONCLUSIONS:
      The high seroprevalence of antibodies to H. pylori in patients with HCV-positive
      liver diseases explains the elevated incidence of peptic ulcer, and warrants
      studies on the pathogenic role in human liver diseases of Helicobacter spp which
      is known to cause chronic hepatitis and hepatocellular carcinoma in mice.

PMID- 14596344
TI  - First two confirmed cases of malignant catarrhal fever in Italy.
AB  - Two cases of sheep-associated malignant catarrhal fever (SA-MCF) in cattle herds
      of Southern Italy are reported. The affected animals, a three-year-old cow and a
      six-month-old calf, developed clinical manifestations resembling those of the
      "head and eye" form of MCF. Serologically, the calf tested positive in an
      indirect immunofluorescent (IIF) assay for the detection of MCF viruses
      antibodies, whereas the cow was found seronegative. One affected animal was from
      a herd housed together with a flock of sheep, while no contact between the herd
      of the affected calf and carrier animals was demonstrated. OvHV-2 viral DNA was
      detected by a PCR test performed on peripheral blood leucocytes (PBL) and tissue
      samples from both the animals, completing the definitive diagnosis of MCF.

PMID- 14596343
TI  - Infectious agents in tissues from spontaneous abortions in the first trimester of
      pregnancy.
AB  - Some evidence suggests that intrauterine infection plays a major role in the
      pathogenesis of early pregnancy loss, but the implication and prevalence of
      microrganisms in the aetiology of spontaneous abortion during the first trimester
      of pregnancy has not yet been well established. In this study, we analysed the
      tissues relative to the product of conception from abortions during the first
      trimester (51 spontaneous abortions and 56 voluntary pregnancy interruptions) in
      women attending the Gynecological Sciences Perinatology and Puericulture
      Department of "Policlinico Umberto I". Specimens were investigated by cultural
      methods for the presence of yeasts, gram positive, gram negative bacteria, and
      genital mycoplasma. By molecular diagnostic procedures, DNA sequences of
      Chlamydia trachomatis, herpes simplex viruses, adenovirus, human papillomaviruses
      and human polyomaviruses BK and JC were searched. None of these agents could be
      found in voluntary pregnancy interruption samples, with the exception of 3.6% of
      specimens positive for adenovirus, whereas spontaneous abortion tissues were
      positive for at least one microrganism by 31.5%. Data analysis showed the
      occurrence of both monomicrobial and polymicrobial infections.

PMID- 14596346
TI  - Incidence and molecular epidemiology of Pseudomonas aeruginosa bacteremias in
      patients with acute leukemia: analysis by pulsed-field gel electrophoresis.
AB  - The incidence and molecular epidemiology of P. aeruginosa bacteremias, were
      monitored in patients with acute leukemia to define mechanisms of possible
      nosocomial transmission. From September 1997 to March 2001 febrile episodes were
      examined and blood isolates of P. aeruginosa were studied employing Pulsed-Field
      gel Electrophoresis (PFGE). Evaluation of DNA correlation was performed according
      to Tenover criteria. A total of 309 febrile episodes occurred in 187 patients. Of
      139 organisms isolated in 116 bacteremias, 48% were gram negative bacilli (GNB);
      P. aeruginosa bacteremias were recorded in 34 (51%) of GNB sepsis. Evaluation of
      DNA correlation showed 2 related in 1997, 7 related in 1998, 10 related in 1999,
      6 related in 2000-2001 (mainly closely and possibly related); therefore isolates
      closely related among themselves were also possibly related with other strains.
      About 60% of patients with related strains were hospitalized in the same room or
      in different rooms but became infected in the same period. Our data suggest a
      horizontal spread among the patients even if other sources were possible. The
      study assessed the usefulness of PFGE in bacteriological epidemiology.

PMID- 14596345
TI  - Detection of resistance to isoniazid by denaturing gradient-gel electrophoresis
      DNA sequencing in Mycobacterium tuberculosis clinical isolates.
AB  - Isoniazid (INH) resistance was genotypically assessed in 104 (37 INH-susceptible,
      67 INH-resistant) genetically unrelated Mycobacterium tuberculosis strains
      cultured in North Italy. The PCR products of selected regions of the katG gene,
      the oxyR-ahpC intergenic region, and the inhA regulatory region were analyzed
      utilizing the double gradient-denaturing gradient gel electrophoresis (DG-DGGE)
      technique and confirmed by DNA sequencing. Mutations were detected in 61 (91%) of
      the INH-resistant strains, the relative frequency of the mutations being 65.7% in
      katG, 23.9% in oxyR-ahpC, and 13.4% in inhA. Previously described alterations,
      invariably associated with drug resistance, accounted for 95.1% of the mutations.
      No alterations were found in the INH-susceptible strains. DG-DGGE analysis and
      DNA sequencing were equally sensitive, but the former is cheaper, easier and more
      robust. Rapid genotypic assessment of INH resistance by means of the methodology
      described here could reasonably be used in clinical mycobacteriology
      laboratories.

PMID- 14596347
TI  - Occurrence of Salmonella typhi and Salmonella paratyphi in Jordan.
AB  - In order to justify the surveillance control system and hygiene policy in Jordan,
      this study evaluated the occurrence of diarrhoea during the period 1988-2000,
      focusing on cases caused by Salmonella typhi and Salmonella paratyphi. From
      January 1988 to December 2000, the number of notified diarrhoeal cases by the
      Ministry of Health in Jordan was 1,399,563 million. Other groups of patients
      confined to the Governorate of Amman was diagnosed at Al-Battikhi Medical
      Laboratories. One-way ANOVA and Least Significant Difference (LSD) were carried
      out for statistical analysis. The number of reported diarrhea cases was
      1,399,563, 53.0% were males, and 47.0% were females, among them, 80.3% were < 20
      years and 19.7%, were > 20 years. Out of 245,255 patients tested for S. typhi and
      S. pararyphi, positive stool culture were 1992 (0.6%). Out of these, 960 (48.2%)
      were males and 1,032 (51.8%) were females (P = 0.028). The highest incidence rate
      (10.8) was observed in the year 1993, while the lowest incidence rate (0.9) was
      found in year 2000. A significant difference (P < 0.001) was found between the
      number of S. typhi and S. Paratyphi cases and year. The seasonal variation was
      also found to be significant (P < 0.0001), with the summer period showing the
      highest incident rate. A significant difference (P < 0.001) was observed between
      number of typhoid and paratyphoid cases and districts. A significance difference
      between number of typhoid and paratyphoid cases with age and sex. The group most
      affected was school age and adolescence. The demographic situation plays an
      important role in reporting typhoid and paratyphoid cases, where there might be
      an urgent indication for a better surveillance control system on water resources
      and disposal systems. S. typhi and S. paratyphi antibiotics resistance pattern
      showed they were resistant to tetracycline (56.0%, 58.0%), ampicillin (45.0%,
      48.0%), trimethoprim (43.0%, 47.0%), cephtazidime (12.0%, 13.5%) chloramphenicol
      (6.8%, 7.2%), gentamycin (3.0%, 4.0%) neomycin (2.1. 1.8%), calvulanic acid
      (augmentin (1.4%, 2.2%) and norofloxacin (0.92%, 1.1%). Susceptibility to
      amikacin, ciprofloxacin, cetfriaxone, ofloxacine, imepenim, cefixime and
      cefotaxime was 100.0%. The increase in percentage of antibiotic resistant strain
      might indicate a need for a further prescribing policy for treatment.

PMID- 14596348
TI  - Detection of isoniazid and rifampin resistance in Mycobacterium tuberculosis
      strains by single-strand conformation polymorphism analysis and restriction
      fragment length polymorphism.
AB  - Anti-Mycobacterium tuberculosis drug-resistance, mainly multi-drug resistance
      (MDR-TB), represents an important public health problem in several countries. Aim
      of our study is to identify the presence of these mutations in M. tuberculosis
      isoniazid- and rifampin-resistant strains isolated in our Institute; to evaluate
      linkage between type of mutation and level of resistance; to determine the
      usefulness of easy molecular techniques for rapid detection of such mutations on
      body specimens. Isoniazid- and rifampin-resistance was tested on 67 M.
      tuberculosis strains by Single-Strand Conformation Polymorphism (SSCP) and
      Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP)
      assays, using HaeIII, PstuI, BsteII, BstuI enzymes. Drug-resistance of control
      strains was determined by cultural techniques (fluorimetry- BACTEC 9120).
      Cultural assay showed isoniazid- and rifampin-resistance in 6.12 and 2%,
      respectively (data confirmed by SSCP assay). Mutation of katG, linked to
      isoniazid resistance, was detected using BstuI enzyme, and mutation of rpoB,
      expression of reduced sensitivity to rifampin, using HaeIII. 15 body specimens,
      M. tuberculosis-positive to conventional assays, were tested by SSCP technique.
      Epidemiologic reports of numerous cases of tuberculosis due to MDR strains induce
      to detect quickly both Mycobacteria and drug-resistance, in order to start prompt
      effective therapy. On this basis, molecular assays are useful for a rapid
      therapeutic decision.

PMID- 14596349
TI  - Epidemiology of leptospirosis: observations on serological data obtained by a
      "diagnostic laboratory for leptospirosis" from 1995 to 2001.
AB  - Serological data on leptospira infection were reported and discussed. From 1995
      to 2001, the blood serum samples of 9885 domestic and wild animals and humans,
      living in Northern and Central Italy, were examined by the macroagglutination
      test (MAT) employing bratislava, ballum, canicola, grippotyphosa,
      icterohaemorrhagiae, pomona, hardjo and tarassovi serovars as antigens.
      Considering sera with > or = 1:400 antibody titers as positive, 674 (6.81%)
      animals scored positive. Sheep, horses, pigs and dogs gave the highest number of
      positive responses, particularly against the serovar bratislava and, for dogs,
      against icterohaemorrhagiae. The percentages of seropositivity observed in the
      most important animal species were: 12.13% in ovine (132 positive among 1088
      tested animals), 11.40% in horses (107 positive animals among 938), 9.46% in
      swine (123 positive animals among 1299), 6.36% in dogs (278 positive animals
      among 4369), 2.39% in wild boars (11 positive animals among 459), 1.39% in deer
      (2 positive animals among 143), 0.48% in cattle (3 positive animals among 626).
      Among 250 human sera examined, 14 (5.60%) scored positive.

PMID- 14596350
TI  - Presence and indigenous nature of Lyme disease in southern Italy.
AB  - Lyme disease is very common in the countries of the northern hemisphere. In Italy
      it is endemic in some regions of the northern part of the country and it is more
      frequent during summer. In Calabria (south Italy) no cases have been reported. To
      document the presence and indigenous nature of Lyme disease in this territory we
      conducted a study from 1999 to 2002. We defined as indigenous cases those with
      erythema migrans with the following characteristics: dimensions equal to or
      greater than 5 cm; localization on an area of the skin where there was a tick
      bite; appearance between 4 and 30 days after the tick bite; appearance in
      patients who had not resided out of Calabria in the previous 3 months. We found
      23 patients with the necessary characteristics to be defined indigenous cases.
      Since 15 of these cases (65.2%) were observed in the October - December trimester
      and no case was found in the July - September trimester, we suspect that in
      Calabria the disease follows a seasonal distribution which differs with respect
      to countries where it is historically endemic.

PMID- 14596351
TI  - Safe and successful endoarterial infusion of liposomal amphotericin B in
      treatment of mucormycosis.
AB  - Mucormycosis is a rare invasive mycotic infection treated by antifungini or
      amphotericin B. We describe the case of a patient with septic fever and a
      necrotic lesion, with phlegmon of medial left thigh. Surgery was performed to
      drain the abscess content and to remove the necrotic tissue; mucormycosis was
      diagnosized by histological and culture tests and treated by intravenous
      amphotericin B. Since the lesion worsened, liposomal amphotericin B was directly
      infused into the left common iliac artery, with progressive improvement, and
      treatment was continued until complete recovery. Therefore, the endoarterial
      infusion of liposomal amphotericin B was a safe and successful treatment of
      advanced lesions of mucormycosis. In such lesions, intravenous general antibiotic
      administration probably is not sufficient to reach the whole infected area.

PMID- 14596352
TI  - Differential induction of TNFalpha and IL-18 in human peripheral blood
      mononuclear cells infected with Leishmania major or Leishmania donovani.
AB  - Several cytokines are involved in the host response to Leishmania. However, the
      role played by cytokines during infection with different species of Leishmania is
      not univocal. In this work, the production of tumor necrosis factor alpha
      (TNFalpha) and interleukin 18 (IL-18) during interaction of human phagocytes with
      Leishmania major or L. donovani was comparatively investigated. Peripheral blood
      mononuclear cells (PBMC) and monocytes from healthy donors were used. The release
      of TNFalpha and IL-18 during infection of cells with different species of
      Leishmania "in vitro" was evaluated. L. donovani induced in both PBMC and
      monocytes significantly more TNFalpha and IL-18 with respect to L. major. The
      amounts of TNFalpha released by PBMC were always significantly higher than those
      released by monocytes of the same donors.

PMID- 14596353
TI  - Drug failure during HIV-1 treatment. New perspectives in monitoring drug
      resistance.
AB  - Since the discovery of 3'-azido-3'deoxthymidine (zidovudine) as an effective
      antiretroviral agent against human immunodeficiency virus type 1 (HIV-1), drug
      therapy has been widely used in the treatment of AIDS. To date, new combination
      therapies have significantly altered the longterm prognosis for HIV-infected
      patients showing a reduction of plasma viral load, associated with clinical and
      immunological recovery. Nevertheless, in various circumstances treatment can fail
      for several reasons, such as patient noncompliance with the therapeutic regimen,
      suboptimal antiviral drug concentrations, drug pharmacokinetics, and virus
      resistance to one or more drugs. Virus drug resistance is the most important
      factor contributing to the failure of antiretroviral therapy. Since some evidence
      indicates that viral resistance and treatment failure are closely linked, this
      brief review explores the routine determination of drug resistance and its
      importance to shed more light on the meaning of mutations correlated to drug
      resistance.

PMID- 14596354
TI  - Recent hypertension guidelines: JNC-7 and 2003 ESH/ESC.

PMID- 14596355
TI  - Role of educational intervention in the management of comorbid depression and
      hypertension.
AB  - To assess the effect of health education on blood pressure control and depression
      symptoms, we conducted a prospective study in 272 patients with essential
      hypertension. Depression symptoms were assessed by the Zung Self-rating
      Depression Scale (SDS). There was no significant difference in the level of
      hypertension and SDS scores between the educational (n = 138) and control (n =
      134) group before the study (p > 0.05). After 12 months of follow-up, the body
      mass index (BMI) was reduced in the educational group (23.6 +/- 2.6 vs 21.4 +/-
      2.2 kg/m2, p < 0.01), but it remained unchanged in the control group. The average
      systolic and diastolic blood pressure were reduced in both groups, but the
      amplitude of systolic blood pressure reduction in the educational group was
      greater than that of the control group (7.9 +/- 2.3 vs 4.2 +/- 2.0 mmHg, p <
      0.01). The incidence of depression (10.9% vs 10.4%) and the average SDS scores
      (32.4 +/- 6.7 vs 33.2 +/- 6.9) were similar between the two groups (p > 0.05).
      However, in the depressed patients who received hypertension education, the
      average systolic (160.2 +/- 12.4 mmHg) and diastolic (89.8 +/- 7.3 mmHg) blood
      pressure was significantly lower than that of the control group (169.1 +/- 16.8
      and 96.8 +/- 13.0 mmHg, respectively, p < 0.01). We conclude that hypertension
      education does not reduce the incidence or symptoms of depression, but it may
      facilitate blood pressure management in patients with clinical depression.

PMID- 14596356
TI  - A Swedish population-based study on the relationship between the SF-36 and health
      utilities to measure health in hypertension.
AB  - The aim of this study was to determine the relationship between a psychometric
      health-related quality-of-life instrument (the SF-36)-and two health utility
      measures [the time trade-off (TTO) and rating scale (RS) methods) among
      hypertensives in a general population. In the analyses were adjusted for
      comorbidity. The study was based on a postal questionnaire that was sent to a
      random sample of 8000 inhabitants aged 20-84 years (response rate 68%) in Uppsala
      County, Sweden, in 1995. The results showed only a moderate correlation between
      the TTO and the RS methods. The different dimensions of SF-36 were overall lower
      correlated with the TTO method than with the RS method. Co-morbidity was not
      associated with the RS or the TTO method among hypertensives. The regression
      equations explained 58% of the variance in RS among hypertensives. The
      corresponding value for the TTO method was about 20%. In conclusion, our study
      found that among hypertensives the SF-36 is low to moderate correlated to the TTO
      and RS methods. Health utilities and psychometric measures represent different
      attributes of health. It is therefore important to be aware of the differences
      between psychometric and utility measures when interpreting results from studies
      using different methods. More work is needed to explicate if health utilities can
      be obtained from the SF-36.

PMID- 14596357
TI  - The Norwegian office-, home-, and ambulatory blood pressure study (NOHA).
AB  - OBJECTIVES: To evaluate the use of ambulatory blood pressure monitoring in
      comparison with home and office blood pressure in every-day general practice.
      METHODS: In a multicenter survey sixty-two practitioners previously unfamiliar
      with ambulatory blood pressure monitoring performed a total of 1162 (mean 18 +/-
      16; range 3-94) 24-h ambulatory- and home blood pressure measurements in
      normotensive subjects or patients with untreated or treated hypertension.
      RESULTS: In subjects with office blood pressure <140/90 mmHg average 24-h
      ambulatory blood pressure (Tenso 24 monitors) was 126/79 mmHg, home blood
      pressure (Tenso Plus semiautomatic sphygmomanometers) was 128/ 84 mmHg, and
      office blood pressure (standard sphygmomanometer) was 130/82 mmHg. Patients with
      office blood pressure > or = 140/90 mmHg had 24-h ambulatory blood pressure
      averaging 141/88 mmHg, home blood pressure 149/93 mmHg, and office blood pressure
      157/95 mmHg. The difference between office-, home-, and ambulatory blood pressure
      increased with age. Expected differences were found between the three blood
      pressure modalities according to indication of examination (borderline -, "white
      coat" -, and therapy refractory hypertension). Indices of hypertension related
      end-organ damage were positively correlated with home and ambulatory blood
      pressure but not with office blood pressure. Overall the performance of home- and
      ambulatory blood pressure in this general practice setting was similar to that
      seen by specialized blood pressure units. CONCLUSION: This study demonstrates the
      practical utility of home- and ambulatory blood pressure measurement in every-day
      general practice. Both methods are easy to introduce and the quality of blood
      pressure data obtained in every-day general practice are comparable to those
      obtained in hypertension clinics and trial centers.

PMID- 14596358
TI  - Interest of home blood pressure measurements (HBPM) to establish degree of
      hypertensive control.
AB  - AIMS: To establish the validity and clinical value of home blood pressure
      measurements (HBPM) in the treatment follow-up of patients with essential
      hypertension to rule out or to confirm poor control of blood pressure obtained in
      the doctor's office with a mercury sphygmomanometer. MATERIAL AND METHODS:
      Observational, cross-sectional study was carried out to validate HBPM in treated
      hypertensive patients poorly controlled by office-based casual blood pressure
      measurements. Measurements were made on 2 consecutive days with six readings
      taken per day. To do this, 2 x 2 tables were drawn up to validate the HBPM using
      ABPM as the reference method. Sensitivity (S), specificity (Sp), positive
      probability quotient (+PQ) and negative probability quotient (-PQ) were
      calculated. The study population (n = 149) was selected by consecutive sampling
      of the hypertensive patients seen in the Vallada Health Centre. Only 124 patients
      could be evaluated. RESULTS: Values obtained with HBPM were: S 97.3% (95% CI 90.4
      99.7%), Sp 62.7% (48.1-75.9%), +PQ 2.61 (1.82-3.73) and -PQ 0.04 (0.01-0.71).
      CONCLUSIONS: Home monitoring of blood pressure is a useful alternative to ABPM to
      rule out office-based poor control of hypertensive patients, but not to confirm
      it.

PMID- 14596359
TI  - Risk factor profile and achievement of treatment goals among hypertensive
      patients from the Israeli Blood Pressure Control (IBPC) program--initial cost
      utility analysis.
AB  - AIMS: Blood pressure (BP) reduction is crucial in reducing cardiovascular
      morbidity and mortality. The IBPC (Israeli Blood Pressure Control) program was
      initiated in order to enhance the control of modifiable risk factors among high
      risk hypertensive patients under follow-up by general practitioners in Israel.
      The cost effectiveness of an intervention program is an important factor in the
      decision-making process of its implementation and therefore was evaluated here.
      The objective of this evaluation is to estimate the costs, monetary savings and
      benefits in terms of QALYs (quality-adjusted life years) that would be expected
      if the program were to be expanded to 100 clinics nationwide, enabling around
      14800 persons to be treated. METHODS: Hypertensive patients were screened in 30
      general practice clinics, supervised by specialists in family medicine, each
      seeing 1000-5000 patients; 50-250 hypertensive patients were diagnosed at each
      participating clinic. BP levels, body mass index (BMI), lipid and glucose levels,
      as well as target organ damage and medications were recorded for all patients.
      RESULTS: A total of 4948 (2079, 42% males) were registered. Mean age was 64.8 +/-
      12 years. After 1 year of follow-up versus baseline, the various parameters were
      as follows: BP control was achieved in 46.4% vs 29% of all hypertensive patients.
      LDL control (JNC VI criteria) was achieved in 41.7% vs 31.2% of all patients.
      Fasting plasma glucose control (glucose < 126 mg/dl) was achieved in 22% vs 19%
      of diabetic patients and 5.2% vs 3.1% of the diabetics had fasting plasma glucose
      levels > 200 mg/dl. Obesity (BMI > 30 kg/m2) was noted in 36.7% vs 43.8% at
      baseline. The cost utility analysis of the reduction in risk factors was
      calculated based on the international dicta applied to the reduction in risk
      factors as a result of treatment. For 100 clinics nationwide and 14800 persons to
      be treated the net saving to health services would be $977993 and the increase in
      QALYs would be 602 years. CONCLUSIONS: Better risk factor control in hypertensive
      patients by general practitioners could reduce morbidity and mortality as well as
      be cost effective.

PMID- 14596360
TI  - Effectiveness of hypertension treatment assessed by blood pressure level achieved
      in primary care setting in Poland.
AB  - The effectiveness of hypertension treatment remains low in many developed
      countries. The aim of our study was to evaluate the treatment effectiveness in
      hypertensives treated by general practitioners (GPs) in Poland. Twenty thousand
      three hundred and five hypertensive patients (mean age 60.1 +/- 12.0 years, 9918
      women, 10 387 men), pharmacologically treated by 677 GPs in Poland, were
      investigated. Blood pressure (BP) in every patient was measured twice, within
      approximately a 5-min interval, in a seated position, using a mercury
      sphygmomanometer, after a rest of at least 10 min. Mean blood pressure from both
      measurements was used for further analysis. Measurements were carried out by a GP
      in the office. Every physician investigated 30 consecutive hypertensive patients.
      Of the investigated hypertensive patients treated, 8.3% had systolic blood
      pressure (SBP) < 140 mmHg and diastolic blood pressure (DBP) < 90 mmHg (7.8% in
      women, 8.8% in men respectively; p > 0.05). Mean SBP in the investigated group
      was 161.9 +/- 20.4 mmHg, 162.7 +/- 20.8 mmHg in women and 161.1 +/- 20.1 mmHg in
      men, respectively; p < 0.05. Mean DBP was 95.4 +/- 11.0 mmHg. The difference
      between mean DBP in women (95.3 +/- 11.0 mmHg) and men (95.5 +/- 11.1 mmHg) was
      not significant, p > 0.05. Mean pulse pressure (PP) for the whole group was 66.5
      +/- 16.3 mmHg. In this cohort, 26.7% of patients were treated with one, 37.6%
      with two, 26.7% with three, 8.2% with four and 0.8% with five antihypertensive
      drugs. Mean number of antihypertensive drugs prescribed for one hypertensive
      patient was 2.2 +/- 1.0. Effectiveness of hypertension treatment by GPs in Poland
      remained unsatisfactory despite frequent implementation of combined
      antihypertensive drug therapy.

PMID- 14596361
TI  - Central and peripheral hemodynamic effects of losartan and in combination with
      hydrochlorothiazide in mild to moderate essential hypertension.
AB  - BACKGROUND: Angiotensin II antagonists have proved to be effective
      antihypertensive agents with organoprotective properties. We aimed to clarify the
      effects of losartan and its combination with hydrochlorothiazide on 24-h blood
      pressures (BPs), central hemodynamics and microcirculation in essential
      hypertension (EH). METHODS: Forty patients with mild to moderate EH were randomly
      allocated to receive losartan 50 mg (group I) or losartan 50 mg in combination
      with hydrochlorothiazide, 12.5 mg (group II). At baseline, week 2 and 8,
      ambulatory BP monitoring (ABPM), central hemodynamics monitoring and
      microcirculation investigation were performed. RESULTS: In both groups, 24-h,
      daytime and night-time systolic (SBP) and diastolic (SBP) significantly decreased
      at week 8. DBP decreased more than SBP. Both drug regimens led to significant
      decrease in total peripheral vascular resistance; stroke and cardiac indexes
      remained unchanged. Losartan and its combination with hydrochlorothiazide
      improved main parameters of microcirculation. The index of microcirculation
      increased, as did the amplitude of cardiodependent and low frequency waves.
      CONCLUSIONS: Losartan monotherapy and losartan in combination with
      hydrochlorothiazide are effective antihypertensive agents. The BP-lowering effect
      is realized through reduction of total peripheral vascular resistance. Moreover,
      both drug regimens significantly improve parameters of microcirculation.

PMID- 14596362
TI  - Candesartan and hydrochlorothiazide in isolated systolic hypertension.
AB  - AIM: We investigated the efficacy and safety of daily candesartan 8/16mg and
      hydrochlorothiazide 12.5 mg as monotherapy and in combination in older patients
      with systolic hypertension. METHODS: The study used a double-blind randomized
      placebo-controlled crossover design. Treatment phases were of 6 weeks duration.
      For inclusion, patients were aged 55-84 years with sitting systolic blood
      pressure (SBP) 160-210 mmHg and diastolic blood pressure (DBP) < 95 mmHg.
      Nineteen patients (11 male, eight female, median age 68 years) completed the
      study. MAJOR FINDINGS: Compared with the placebo phase, clinic and ambulatory SBP
      was significantly reduced with both dose-adjusted candesartan and fixed-dose
      hydrochlorothiazide as monotherapy, the effect of candesartan being greater than
      that of hydrochlorothiazide. In combination, the effects of the two drugs were
      additive. Both drugs were well tolerated either as monotherapy or in combination.
      CONCLUSION: Both candesartan and a low dose of hydrochlorothiazide are effective
      and well-tolerated antihypertensive agents in isolated systolic hypertension with
      additive effects in combination. Candesartan was more effective than
      hydrochlorothiazide, although it is possible that dose adjustment only of
      candesartan could have enhanced its relative effectiveness.

PMID- 14596363
TI  - Hypertension and coronary heart disease.

PMID- 14596364
TI  - Renal angiotensin II receptors, hyperinsulinemia, and obesity.
AB  - Angiotensin II, via activation of AT1 receptors in the kidney regulates
      sodium/fluid homeostasis and blood pressure. An exaggerated action of angiotensin
      II mediated via activation of AT1 receptors has been implicated in the increased
      renal sodium retention and the resetting of the pressure natriuresis in obesity
      related hypertension. Treatment of obese Zucker rats with AT1 receptor blockers
      reduces blood pressure to a greater extent and produces greater natriuresis.
      Also, there is an increased membranal AT1 receptor numbers and angiotensin II
      produces greater activation of sodium transporters in the isolated tubules from
      obese Zucker rats. Interestingly, AT2 receptors, which are believed to be
      beneficial to the renal and cardiovascular function in terms of their action on
      kidney and blood vessels, are greatly increased in proximal tubular membranes of
      obese Zucker rats. Whole animal and in vitro studies indicate that higher plasma
      insulin level, generally associated with obesity, is responsible for the up
      regulation of both AT1 and AT2 receptors in the kidney. Determining the
      consequence of selective blocking of AT1 receptors and/or activation of the AT2
      receptors on renal and cardiovascular function, and the effect of lowering
      insulin on these receptors present an important area of further investigation in
      obesity.

PMID- 14596365
TI  - Effects of autogenic training and antihypertensive agents on circadian and
      circaseptan variation of blood pressure.
AB  - Even when the daily blood pressure mean is acceptable, too large a circadian
      amplitude of blood pressure largely increases cardiovascular disease risk.
      Autogenic training (N = 11), a non-pharmacologic intervention capable of lowering
      an excessive blood pressure variability, may be well-suited for MESOR
      normotensive patients diagnosed with circadian-hyper-amplitude-tension (CHAT).
      Not all anti-hypertensive drugs affect blood pressure variability. Accordingly,
      long-acting carteolol (N = 11) and/or atenolol (N = 8) may be preferred to
      captopril retard (N = 13), nilvadipine (N = 8), or amlodipine (N = 7) for midline
      estimating statistic of rhythm (MESOR)-hypertensive patients with CHAT.
      Prospective outcome studies are needed to assess whether the relative merits of
      these treatments are in keeping with their effects on blood pressure and blood
      pressure variability.

PMID- 14596366
TI  - Coculture of vascular endothelial cells and smooth muscle cells from
      spontaneously hypertensive rats.
AB  - The effect of endothelium-released vasoactive factors on vascular smooth muscle
      cell (VSMC) proliferation was studied in a coculture system. Isolated aortic
      endothelial cells and smooth muscle cells from 4-week-old spontaneously
      hypertensive rats (SHR) and age-matched Wistar-Kyoto (WKY) rats were cocultured.
      After coculture, the VSMC proliferation rate was examined by 3H-thymidine
      incorporation assay and the levels of the vasoactive factors in medium were
      determined by enzyme immunoassay (EIA). The results indicate that the
      proliferation rate of VSMCs in SHR was significantly higher than in WKY rats when
      VSMCs were cultured alone. When SHR vascular endothelial cells (VECs) were
      cocultured with VSMCs, the proliferation rate of SHR VSMCs was enhanced; however,
      there was no growth promoting effect in WKY VSMCs. When WKY VECs were cocultured
      with VSMCs, no VSMC proliferation effect was observed. When VSMCs were cultured
      alone, the endothelin-1 (ET-1) secretion in SHR was significantly higher than in
      WKY rats. When VECs and VSMCs were cocultured, the ET-1 concentration increased
      in both SHR VEC and WKY VEC coculture groups in a similar manner; but the SHR
      VECs tended to release more thromboxaneA2 (TXA2) and less PGI2 than WKY VECs.
      These results suggest that some kind of interaction between SHR VSMCs and SHR
      VECs is responsible for the high proliferation of SHR VSMCs but not the effects
      of SHR VECs per se.

PMID- 14596367
TI  - Effects of losartan and enalapril at different doses on cardiac and renal
      interstitial matrix in spontaneously hypertensive rats.
AB  - We have evaluated the effects of an ACE inhibitor, enalapril (ENA) and of an
      angiotensin II receptor blocker, losartan (LOS), administered either at
      hypotensive or non-hypotensive dosage, on the cardiac and renal structure of
      spontaneously hypertensive rats (SHR). Forty-eight rats were included in the
      study: eight SHR were treated with low-dose (ld, 1 mg/kg/day) ENA; eight with low
      dose (ld, 0.5 mg/kg/day) LOS; eight with high-dose (hd, 25 mg/kg/day) ENA; eight
      with high-dose (hd, 15 mg/kg/day) LOS; while eight Wistar-Kyoto (WKY) and eight
      SHR were kept untreated (unt). Treatment was given from the 4th to the 12th week
      of age. Systolic blood pressure (SBP) was measured non-invasively every week. The
      left ventricular weight to body weight (RLVM) and the left + right kidney weight
      (RKW) to body weight was measured, and the cardiac and glomerular interstitial
      collagen content was evaluated using sirius red staining and image analysis. In
      addition, cardiac metalloproteinases activity (43 kDa MMP, MMP-2, and MMP-9) was
      evaluated by zymography. A significant reduction in RLVM was observed in SHR
      given ENA hd or LOS hd. Cardiac collagen was significantly reduced in SHR ENA hd
      and SHR LOS hd as well as in SHR LOS ld, but not in SHR ENA ld. The 43 kDa MMP
      collagenase activity was greater in WKY unt compared with SHR unt, being
      normalized only in SHR ENA hd. The gelatinase activity of MMP-9 showed a trend
      similar to 43 kDa MMP, but differences between SHR and WKY unt were only of
      borderline statistical significance. No difference among groups was observed in
      MMP-2 activity. No significant differences in RKW was observed between groups.
      However, the collagen content in the glomerular perivascular space was
      significantly reduced in all treated groups, including those given ld, compared
      with SHR unt. In conclusion, LOS and ENA showed a similar preventive effect on
      the increase of RLVM in SHR, but, at least in part, different effects on the
      extracellular matrix in different organs, being cardiac collagen less sensitive
      to low dose (ld) ACE inhibition.

PMID- 14596368
TI  - Determinants of the white-coat effect in normotensives and never-treated mild
      hypertensives.
AB  - The prognostic significance of the white-coat effect (WCE) is unclear. Knowledge
      of the predictors of the WCE may help illuminate the clinical significance of
      this phenomenon. The purpose of this study was to (i) compare characteristics of
      subjects demonstrating a WCE, those not demonstrating a WCE, and those
      demonstrating a reverse WCE and (ii) determine clinical features that may
      influence the size of the WCE. Forty-one subjects with normotension or mild
      hypertension who had never been treated with antihypertensive medications were
      recruited for the study. All subjects underwent a battery of anthropometrical
      measurements and clinic blood pressure (BP) measurements. To calculate arterial
      compliance, impedance cardiography was used to measure resting stroke volume in
      each subject. All subjects performed a laboratory mental stress protocol to
      determine the size of the BP reactivity. Ambulatory blood pressure (ABP) profiles
      were studied in each subject with the use of an oscillometric ABP recorder. White
      coat effect was determined by subtracting the awake period of the ambulatory
      systolic blood pressure (SBP) from the clinical SBP. Subjects were grouped
      according to the size of their WCE. Those who showed a WCE of 5 mmHg and above
      were assigned to the WCE group; those who showed a WCE of between -5 and 5 mmHg
      were assigned to the no white coat effect (NWCE) group; those who exhibited a WCE
      of -5 mmHg and lower were assigned to the reverse white-coat effect (RWCE) group.
      Subjects with a positive WCE had significantly higher body mass index (BMI) than
      those without a WCE and those with a RWCE. The WCE group had significantly higher
      clinic SBP and heart rate (HR) than the RWCE group. Arterial compliance was
      significantly lower in the WCE group as compared to the NWCE group and the RWCE
      group. The three groups had comparable ABP profiles. In terms of BP variability,
      the increase in SBP in response to mental stress did not differ among the three
      study groups nor did the 24-hour and awake BP variability. For the sample as a
      whole, clinic HR and clinic-ambulatory SBP difference were higher and arterial
      compliance were lower in women than in men. Furthermore, clinic SBP significantly
      correlated with the systolic WCE (r = 0.40, P = 0.009). When men and women were
      analyzed separately, the correlation between clinic SBP and the systolic WCE was
      significant in women (r = 0.63, P = 0.001) but not in men (P = 0.95). Multiple
      linear regression showed that sex (P = 0.013) and clinical SBP (P = 0.003) were
      the only two variables that significantly influenced the systolic WCE. These two
      variables together accounted for 29% of the variation in the systolic WCE. In
      conclusion sex and clinic BP are two major determinants of the WCE. The results
      of this study indicate that WCE is not related to higher stress reactivity or
      higher BP variability.

PMID- 14596370
TI  - Chinese herbals reach scientific efficacy.

PMID- 14596369
TI  - Age-related decline in spatial learning and memory: attenuation by captopril.
AB  - Spontaneously hypertensive rats (SHR) compared to normotensive rats display an
      accelerated decline in spatial learning and memory. However, few studies have
      systematically examined the independent contribution of hypertension vs. other
      age-related mechanisms to this decline. The present study uses a repeated
      acquisition water maze task to test the hypothesis that hypertension and/or the
      presence of angiotensin II can accelerate the age-related decrease of spatial
      learning and memory in rats. We have previously shown that both SHR and Wistar
      Kyoto rats (WKY) display age-related decreases in spatial learning and memory;
      however, the rate of decline differs between the strains. The present results
      demonstrate that compared to young rats of the same strain, learning and memory
      in SHR declines significantly already at 12 months of age, and at 24 months of
      age both SHR and WKY rats are severely impaired in the water maze task. Lifetime
      treatment of either SHR or WKY with the antihypertensive drug captopril [an
      angiotensin converting enzyme (ACE) inhibitor] significantly attenuates the age
      related impairment in learning and memory. In contrast, chronic treatment of SHR
      with captopril from 6 months of age only modestly decreases the decline in
      learning and memory. Whereas lifetime treatment with the vasodilator drug
      hydralazine also reduces arterial pressure in SHR, this treatment does not
      significantly preserve learning in 24-month-old SHR. Together, the data suggest
      captopril can delay the decline in spatial learning and memory in both aging SHR
      and WKY. Further, the results indicate that the memory enhancing effects of
      captopril are not primarily the due to the ability of captopril to lower blood
      pressure.

PMID- 14596371
TI  - Preventing the tragedy of neonaticide.
AB  - Denying a pregnancy can result in consequences as tragic as neonaticide--the
      killing of an infant in the first 24 hours of life. Between 150 and 300
      neonaticides are committed each year but the actual prevalence of pregnancy
      denial is unknown. Adolescents are especially vulnerable to pregnancy denial
      because the unexpected event creates such enormous anxiety and fear for them.
      Pregnancy denial often eludes parents, teachers, and health care providers.
      Nurses can advocate for resources and pregnancy screening in primary care
      settings, and help educate parents and teachers about the problem.

PMID- 14596372
TI  - Lay home visiting may improve pregnancy outcomes.
AB  - Home visiting may be a promising strategy to improve pregnancy outcomes, and home
      visiting by lay workers may be more accepted by pregnant women. Lay workers may
      impact on social and environmental risk factors as well as on health care
      utilization. As with any primary prevention strategy, these programs may be more
      successful if implemented with responsibility shared between the health care
      system and the community. This article reviews the state of the science related
      to lay home visiting during pregnancy in the United States. Using a variety of
      search terms, an exhaustive review of the literature was conducted using several
      large electronic databases. Studies of lay home visiting during pregnancy have
      documented mixed results. Many weaknesses exist in the studies available,
      including use of descriptive or quasi-experimental designs in most of the
      studies, absence of a clearly specified set of interventions, and lack of cost
      analysis. Gaps in our knowledge of the impact of lay home visitors on pregnancy
      outcomes persist.

PMID- 14596373
TI  - Form prayer and nursing care: Christian perspectives.
AB  - This article, offers a few forms of prayer that might be helpful in specific
      patient care situations.

PMID- 14596374
TI  - Investigating sleep disturbances in adults with rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation
      and joint involvement. Most adults with RA experience sleep disturbances,
      including longer times before falling asleep, numerous awakenings during the
      night, and early morning wakening, resulting in excessive daytime sleepiness and
      fatigue. This article will review what is known about sleep disturbances and the
      biologic basis in adults with RA, the influence of ovarian hormone levels in
      women with RA, how medications may influence sleep in RA, and complementary and
      alternative therapies that may be useful in reducing sleep disturbances.

PMID- 14596375
TI  - Attaining successful weight loss with an ideal macronutrient balance.
AB  - A dramatic increase in the number of people who are overweight or obese in this
      country presents a growing public health problem. Successful weight loss requires
      diet, physical activity, and behavior modification interventions. Weight loss
      diets with distinctively different macronutrient profiles have resulted in short
      term weight loss. There is great interest in identifying the most effective
      strategies to achieve long-term weight loss. Individualizing weight loss
      interventions, including diet, will be important to facilitate significant weight
      loss on a population basis. Nurses and nurse practitioners can play an integral
      role in supporting their patient's weight loss efforts.

PMID- 14596376
TI  - Evaluating the WEB training program for cancer screening in Native American
      women.
AB  - The Native Women Enjoying the Benefit (WEB) program trains nurses to perform
      breast and cervical cancer screening examinations for Native American women.
      Several evaluations have shown that the program improves nurses' knowledge and
      skills, and nurses value its positive impact on clinic, nurse, and patient
      behaviors. Beyond effectiveness, program longevity often rests upon equilibrium
      that results from alignment between a program's values and principles with those
      of its sponsoring organization and pertinent surrounding environments. We
      examined how Native WEB values align with those of its 2 most relevant
      environments-the medical institution (immediate environment) that sponsors it and
      the broader health care context (distal environment). We found that social
      justice views articulated in Catholic social teaching served as a convenient
      synthesis of the 2 environments' values and principles. We used this conception
      of social justice to determine whether the Native WEB program reflected the
      perspectives of its immediate and distal environments.

PMID- 14596377
TI  - "You mean nurses are supposed to do this ?".

PMID- 14596378
TI  - Relating cause and effect.

PMID- 14596379
TI  - Short-term disability, long term disability, Social Security Disability
      Insurance, and Family Medical Leave Act--relationship to case management
      practice.

PMID- 14596380
TI  - Sleep among shiftworkers--a priority for clinical practice and research in
      occupational health nursing.

PMID- 14596381
TI  - Disabler: a game occupational health nurses cannot afford to play.
AB  - The dynamics of the Disabler game are complex, not always recognizable, and less
      than easily manageable. Awareness of the game and a willingness to avoid direct
      participation can enhance injured worker rehabilitation and decrease costs
      associated with lost time and productivity. Not playing the Disabler game can
      make the role of the occupational health nurse more rewarding. The game requires
      the field upon which to play, and effectively supported DMPs can help eliminate
      those playing fields.

PMID- 14596382
TI  - Organizational factors related to safety in a psychiatric hospital: employee
      perceptions.
AB  - Physical assaults on mental health care workers by aggressive patients were the
      leading cause of occupational injuries to staff working in a community
      psychiatric hospital. More than dollar 1 million was estimated to be lost in 1
      year because of these occupational injuries. This problem was assessed by
      examining the organizational factors related to safety at the hospital. The cross
      sectional survey design measured the perceptions of mental health care workers
      about the commitment of management to safety (i.e., safety climate). Overall,
      results indicated the subscale for safety climate was high (3.77 +/- .66 [mean +/
      SD] on a 5 scale), given the magnitude of recalled incidents and injuries
      involving patients against staff. Safety climate was associated with three
      variables that included administrative controls, occupational stress, and job
      task demands. Results of the study were useful in determining specific changes
      for improving safety. The study findings demonstrated the practicality and
      feasibility of in-house assessments to diagnose areas that require attention,
      support, and improvement.

PMID- 14596383
TI  - Communicating hearing loss information to young children effectiveness of lecture
      and printed materials.
AB  - Developing positive attitudes and behaviors toward hearing loss prevention is
      more effective the earlier it begins. This study evaluated two training
      techniques for educating young children about noise and hearing loss. Third grade
      students from seven Pennsylvania elementary schools received either no
      intervention between the pre-tests and post-tests, a lecture about hearing loss,
      or an informational bookmark along with the same lecture. A 10 item quiz was
      administered as a pre-test and post-test to assess changes in knowledge. Scores
      on the quiz improved the most for the lecture intervention groups regardless of
      whether they received the bookmark. Adding the bookmark did not have a
      significant effect on knowledge gain. The findings reinforce the value of
      providing an educational foundation along with communication products.

PMID- 14596384
TI  - Holistic self care: strategies for initiating a personal assessment.
AB  - To be fully present for clients, occupational health nurses must assume
      responsibility for meeting their own self care needs. To promote holistic health
      care, occupational health nurses must assess personal values, priorities, and
      responsibilities. This can be accomplished by completing a personal assessment
      focusing on current use of holistic modalities. To implement a plan for holistic
      self care, nurses can write goals, set intentions, be open to holistic
      modalities, begin with small changes, recognize feelings, pay attention to
      breathing and self talk, simplify their lives, build support systems, and apply
      self care at work.

PMID- 14596385
TI  - Tips to ease the symptoms of menopause at work.

PMID- 14596386
TI  - Strengthening the health services research to reduce racial and ethnic
      disparities in health care.

PMID- 14596387
TI  - Socioeconomic status and the fates of adolescents.

PMID- 14596389
TI  - Using claims data to examine mortality trends following hospitalization for heart
      attack in Medicare.
AB  - OBJECTIVE: To see if changes in the demographics and illness burden of Medicare
      patients hospitalized for acute myocardial infarction (AMI) from 1995 through
      1999 can explain an observed rise (from 32 percent to 34 percent) in one-year
      mortality over that period. DATA SOURCES: Utilization data from the Centers for
      Medicare and Medicaid Services (CMS) fee-for-service claims (MedPAR, Outpatient,
      and Carrier Standard Analytic Files); patient demographics and date of death from
      CMS Denominator and Vital Status files. For over 1.5 million AMI discharges in
      1995-1999 we retain diagnoses from one year prior, and during, the case-defining
      admission. STUDY DESIGN: We fit logistic regression models to predict one-year
      mortality for the 1995 cases and apply them to 1996-1999 files. The CORE model
      uses age, sex, and original reason for Medicare entitlement to predict mortality.
      Three other models use the CORE variables plus morbidity indicators from well
      known morbidity classification methods (Charlson, DCG, and AHRQ's CCS).
      Regressions were used as is--without pruning to eliminate clinical or statistical
      anomalies. Each model references the same diagnoses--those recorded during the
      pre- and index admission periods. We compare each model's ability to predict
      mortality and use each to calculate risk-adjusted mortality in 1996-1999.
      PRINCIPAL FINDINGS: The comprehensive morbidity classifications (DCG and CCS) led
      to more accurate predictions than the Charlson, which dominated the CORE model
      (validated C-statistics: 0.81, 0.82, 0.74, and 0.66, respectively). Using the
      CORE model for risk adjustment reduced, but did not eliminate, the mortality
      increase. In contrast, adjustment using any of the morbidity models produced
      essentially flat graphs. CONCLUSIONS: Prediction models based on claims-derived
      demographics and morbidity profiles can be extremely accurate. While one-year
      post-AMI mortality in Medicare may not be worsening, outcomes appear not to have
      continued to improve as they had in the prior decade. Rich morbidity information
      is available in claims data, especially when longitudinally tracked across
      multiple settings of care, and is important in setting performance targets and
      evaluating trends.

PMID- 14596388
TI  - Disparities in adolescent health and health care: does socioeconomic status
      matter?
AB  - DATA COLLECTION/EXTRACTION METHODS: National household survey. DATA SOURCES/STUDY
      SETTING: We analyzed data on 12,434 adolescents (10 through 18 years old)
      included in the 1999 and 2000 editions of the National Health Interview Survey.
      STUDY DESIGN: We assessed the presence of income gradients using four income
      groups. Outcome variables included health status, health insurance coverage,
      access to and satisfaction with care, utilization, and unmet health needs.
      PRINCIPAL FINDINGS: After adjustment for confounding variables using multivariate
      analysis, statistically significant disparities were found between poor
      adolescents and their counterparts in middle- and higher-income families for
      three of four health status measures, six of eight measures of access to and
      satisfaction with care, and for six of nine indicators of access to and use of
      medical care, dental care, and mental health care. CONCLUSION: Our analyses
      indicate adolescents in low-income families remain at a disadvantage despite
      expansions of the Medicaid program and the comparatively new State Children's
      Health Insurance Program (SCHIP). Additional efforts are needed to ensure
      eligible adolescents are enrolled in these programs. Nonfinancial barriers to
      care must also be addressed to reduce inequities.

PMID- 14596390
TI  - How state-funded home care programs respond to changes in Medicare home health
      care: resource allocation decisions on the front line.
AB  - OBJECTIVE: To examine how case managers in a state-funded home care program
      allocate home care services in response to information about a client's Medicare
      home health care status, with particular attention to the influence of work
      environment. DATA SOURCES/STUDY SETTING: Primary data collected on 355 case
      managers and 26 agency directors employed in June 1999 by 26 of the 27 regional
      agencies administering the Massachusetts Home Care Program for low-income elders.
      STUDY DESIGN: Data were collected in a cross-sectional survey study design. A
      case manager survey included measures of work environment, demographics, and
      factorial survey vignette clients (N = 2,054), for which case managers assessed
      service eligibility levels. An agency director survey included measures of
      management practices. DATA COLLECTION/EXTRACTION METHODS: Hierarchical linear
      models estimated the effects of work environment on the relationship between
      client receipt of Medicare home health care and care plan levels while
      controlling for case-mix differences in agencies' clients. PRINCIPAL FINDINGS:
      Case managers did not supplement extant Medicare home health services, but did
      allocate more generous service plans to clients who have had Medicare home health
      care services recently terminated. This finding persisted when controlling for
      case mix and did not vary by work environment. Work environment affected overall
      care plan levels. CONCLUSIONS: Study findings indicate systematic patterns of
      frontline resource allocation shaping the relationships among community-based
      long-term care payment sources. Further, results illustrate how nonuniform
      implementation of upper-level initiatives may be partially attributed to work
      environment characteristics.

PMID- 14596391
TI  - Expanding public health insurance to parents: effects on children's coverage
      under Medicaid.
AB  - OBJECTIVE: To assess whether expanding public health insurance coverage to
      parents leads to increases in Medicaid participation among children. DATA
      SOURCES/STUDY SETTING: Study uses data from the 1997 and 1999 National Survey of
      America's Families. Insurance coverage of children eligible for Medicaid under
      the poverty-related expansions is analyzed. STUDY DESIGN: We conduct two
      analyses. In the first, we examine the cross-sectional difference regarding
      whether Medicaid participation is higher for children eligible for Medicaid under
      the poverty-related expansions when states expand public health insurance
      programs to cover their parents. In the second, we use a difference-in-difference
      approach to assess whether the expansion of the Medicaid program to cover parents
      in Massachusetts led to an increase in Medicaid coverage among children between
      1997 and 1999 relative to changes that occurred in the rest of the nation. DATA
      COLLECTION/EXTRACTION METHODS: The analysis relies on a detailed Medicaid and
      SCHIP eligibility simulation model that identifies children surveyed on the NSAF
      who are eligible for Medicaid under the poverty-related expansions. PRINCIPAL
      FINDINGS: Children who reside in states that expanded public health insurance
      programs to parents participate in Medicaid at a rate that is 20 percentage
      points higher than of those who live in states with no expansions. The
      Massachusetts expansion in coverage to parents led to a 14 percentage point
      increase in Medicaid coverage among children due principally to reductions in
      uninsurance among already eligible children. CONCLUSIONS: Expanding public health
      insurance coverage to parents has benefits to children in the form of increased
      participation in Medicaid.

PMID- 14596392
TI  - Methods for using Medicare data to compare procedure rates among Asians, blacks,
      Hispanics, Native Americans, and whites.
AB  - OBJECTIVE: Small sample sizes in Asian, Hispanic, and Native American groups and
      misreporting of race/ethnicity across all groups (including blacks and whites)
      limit the usefulness of racial/ethnic comparisons based on Medicare data. The
      objective of this paper is to compare procedure rates for these groups using
      Medicare data, to assess how small sample size and misreporting affect the
      validity of comparisons, and to compare rates after correcting for misreporting.
      DATA: We use 1997 physician claims data for a 5 percent sample of Medicare
      beneficiaries aged 65 and older to study cardiac procedures and tests. STUDY
      DESIGN: We calculate age and sex-adjusted rates and confidence intervals by
      race/ethnicity. Confidence intervals are compared among the groups. Out-of-sample
      data on misreporting of race/ethnicity are used to assess potential bias due to
      misreporting, and to correct for the bias. PRINCIPAL FINDINGS: Sample sizes are
      sufficient to find significant ethnic and racial differences for most procedures
      studied. Blacks' rates tend to be lower than whites. Asian and Hispanic rates
      also tend to be lower than whites', and about the same as blacks'. Sample sizes
      for Native Americans are very small (about .1 percent of the data); nonetheless,
      some significant differences from whites can still be identified. Biases in rates
      due to misreporting are small (less than 10 percent) for blacks, Hispanics, and
      whites. Biases in rates for Asians and Native Americans are greater, and exceed
      20 percent for some procedures. CONCLUSIONS: Sample sizes for Asians, blacks, and
      Hispanics are generally adequate to permit meaningful comparisons with whites.
      Implementing a correction for misreporting makes Medicare data useful for all
      ethnic groups. Misreporting race/ethnicity and small sample sizes do not
      materially limit the usefulness of Medicare data for comparing rates among racial
      and ethnic groups.

PMID- 14596393
TI  - Case-mix adjusting performance measures in a veteran population: pharmacy- and
      diagnosis-based approaches.
AB  - OBJECTIVE: To compare the rankings for health care utilization performance
      measures at the facility level in a Veterans Health Administration (VHA) health
      care delivery network using pharmacy- and diagnosis-based case-mix adjustment
      measures. DATA SOURCES/STUDY SETTING: The study included veterans who used
      inpatient or outpatient services in Veterans Integrated Service Network (VISN) 20
      during fiscal year 1998 (October 1997 to September 1998; N = 126,076).
      Utilization and pharmacy data were extracted from VHA national databases and the
      VISN 20 data warehouse. STUDY DESIGN: We estimated concurrent regression models
      using pharmacy or diagnosis information in the base year (FY1998) to predict
      health service utilization in the same year. Utilization measures included bed
      days of care for inpatient care and provider visits for outpatient care.
      PRINCIPAL FINDINGS: Rankings of predicted utilization measures across facilities
      vary by case-mix adjustment measure. There is greater consistency within the
      diagnosis-based models than between the diagnosis- and pharmacy-based models. The
      eight facilities were ranked differently by the diagnosis- and pharmacy-based
      models. CONCLUSIONS: Choice of case-mix adjustment measure affects rankings of
      facilities on performance measures, raising concerns about the validity of
      profiling practices. Differences in rankings may reflect differences in
      comparability of data capture across facilities between pharmacy and diagnosis
      data sources, and unstable estimates due to small numbers of patients in a
      facility.

PMID- 14596394
TI  - Working more productively: tools for administrative data.
AB  - OBJECTIVE: This paper describes a web-based resource
      (http://www.umanitoba.ca/centres/mchp/concept/) that contains a series of tools
      for working with administrative data. This work in knowledge management
      represents an effort to document, find, and transfer concepts and techniques,
      both within the local research group and to a more broadly defined user
      community. Concepts and associated computer programs are made as "modular" as
      possible to facilitate easy transfer from one project to another. STUDY
      SETTING/DATA SOURCES: Tools to work with a registry, longitudinal administrative
      data, and special files (survey and clinical) from the Province of Manitoba,
      Canada in the 1990-2003 period. DATA COLLECTION: Literature review and analyses
      of web site utilization were used to generate the findings. PRINCIPAL FINDINGS:
      The Internet-based Concept Dictionary and SAS macros developed in Manitoba are
      being used in a growing number of research centers. Nearly 32,000 hits from more
      than 10,200 hosts in a recent month demonstrate broad interest in the Concept
      Dictionary. CONCLUSIONS: The tools, taken together, make up a knowledge
      repository and research production system that aid local work and have great
      potential internationally. Modular software provides considerable efficiency. The
      merging of documentation and researcher-to-researcher dissemination keeps costs
      manageable.

PMID- 14596395
TI  - Assessing the validity of insurance coverage data in hospital discharge records:
      California OSHPD data.
AB  - OBJECTIVE: To assess the accuracy of data on "expected source of payment" in the
      patient discharge database compiled by the California Office of Statewide Health
      Planning and Development (OSHPD). DATA SOURCES: The OSHPD discharge data for the
      years 1993 to 1996 linked with administrative data from the University of
      California (UC) health benefits program for the same years. The linked dataset
      contains records for all stays in California hospitals by UC employees, retirees,
      and spouses. STUDY DESIGN: The accuracy of the OSHPD data is assessed using cross
      tabulations of insurance type as coded in the two data sources. The UC
      administrative data is assumed to be accurate, implying that differences between
      the two sources represent measurement error in the OSHPD data. We cross-tabulate
      insurance categories and analyze the concordance of dichotomous measures of
      health maintenance organization (HMO) enrollment derived from the two sources.
      PRINCIPAL FINDINGS: There are significant coding errors in the OSHPD data on
      expected source of payment. A nontrivial percentage of patients with preferred
      provider organization (PPO) coverage are erroneously coded as being in HMOs, and
      vice versa. The prevalence of such errors increased after OSHPD introduced a new
      expected source of payment category for PPOs. Measurement problems are especially
      pronounced for older patients. Many patients over age 65 who are still covered by
      a commercial insurance plan are erroneously coded as having Medicare coverage.
      This, combined with the fact that during the period we analyzed, Medicare HMO
      enrollees and beneficiaries in the fee-for-service (FFS) program are combined in
      a single payment category, means that the OSHPD data provides essentially no
      information on insurance coverage for older patients. CONCLUSIONS: Researchers
      should exercise caution in using the expected source of payment in the OSHPD
      data. While measures of HMO coverage are reasonably accurate, it is not possible
      in these data to clearly identify PPOs as a distinct insurance category. For
      patients over age 65, it is not possible at all to distinguish among alternative
      insurance arrangements.

PMID- 14596396
TI  - 8-Hydroxyquinoline derivative as a fluorescent chemosensor for zinc ion.
AB  - 8-Hydroxyquinoline derivative 1 as a fluorescent chemosensor for Zn2+ was
      synthesized. Because Cd2+ is often found with Zn2+ in the environment and can
      form fluorescent complexes with chelating fluorophores, a potentially important
      property of chemosensors for Zn2+ is their selectivity for Zn2+ over Cd2+. The
      Zn2+ or Cd2+ complexes of 1 gave an emission band from the 1:1 complex, but the
      fluorescence intensity for Cd2+ was a half of that for Zn2+. Ligand 1 is suited
      for use as a fluorescent chemosensor for Zn2+.

PMID- 14596397
TI  - Piezo electric sensor for endocrine-disrupting chemicals using receptor-co-factor
      interaction.
AB  - In vitro screening assays are useful techniques for the determination of receptor
      mediated activities in environmental samples. In order to define whether
      environmental chemicals act as an agonist or antagonist to the human estrogen
      receptor (hER), we have constructed a biosensor based on ligand-inducible
      interactions between hER and relative proteins on a quartz crystal microbalance
      (QCM). The his-tagged proteins, which were expressed in E. coli by recombinant
      DNA technology, were immobilized on an Au-electrode with Ni(II)-mediated
      chemisorption using the histidine tag and thiol-modified iminodiacetic acid. The
      resonance-frequency change of the protein-modified electrode was caused by
      association or dissociation with the hER relative proteins on the surface in the
      presence of estrogen. These results suggest that this sensor is applicable as a
      large-scale screening tool for estrogenic compounds.

PMID- 14596398
TI  - Isotope dilution analysis of selenite and selenate in natural water using
      microwave-induced nitrogen plasma mass spectrometry.
AB  - Isotope dilution analysis of the sub-microg l(-1) levels of selenite and selenate
      in natural water samples by microwave-induced nitrogen plasma mass spectrometry
      (MIP-MS) was performed. An appropriate amount of a spike solution containing 78Se
      selenite and 78Se-selenate was added to the natural water sample to be analyzed.
      Both analytes in the water were then concentrated simultaneously by passing the
      sample through a column that was filled with an anionic exchange resin. After the
      concentration process, all of the selenite and some of the selenate on the resin
      were eluted by 0.03 M nitric acid. The residual selenate was eluted by 0.13 M
      nitric acid. The eluted sample solutions were injected into MIP-MS, and isotope
      dilution analyses were carried out. Selenite and selenate concentrations as low
      as 0.01 microg l(-1) in the natural water sample were successfully determined by
      the proposed method.

PMID- 14596400
TI  - Sound-producing sand in Japan: major element composition and its minerals
      determined by X-ray diffraction and X-ray fluorescence.
AB  - The major element composition, including two kinds of clay minerals and moisture
      content of sound-producing sand are reported for the first time. Sand from 33
      beaches in Japan has been found to make sound. Ten sound-producing beaches were
      selected to compare with silent beach sand. Both sound-producing sand and silent
      beach sand are mostly composed of quartz and feldspar. The range of SiO2 content
      of sound-producing sand is not different from silent sand samples. This indicates
      that a high quartz content is not necessary to produce sound, although more than
      60 weight percent of quartz is necessary. One silent sand recovered its sound
      after a 3.5 percent HNO3 treatment. Also, a small portion of clay minerals was
      found. A clean grain surface is a necessary factor for sand to produce sound.
      Illite was found in all silent sand samples.

PMID- 14596399
TI  - Determination of benzene, toluene, ethylbenzene and xylene in river water by
      solid-phase extraction and gas chromatography.
AB  - A rapid and reproducible method is described that employs solid-phase extraction
      (SPE) using dichloromethane, followed by gas chromatography (GC) with flame
      ionization detection for the determination of benzene, toluene, ethylbenzene,
      xylene and cumene (BTEXC) from Buriganga River water of Bangladesh. The method
      was applied to detect BTEXC in a sample collected from the surface, or 5 cm depth
      of water. Two-hundred milliliters of n-hexane-pretreated and filtered water
      samples were applied directly to a C18 SPE column. BTEXC were extracted with
      dichloromethane and the BTEX concentrations were obtained to be 0.1 to 0.37
      microg ml(-1). The highest concentration of benzene was found as 0.37 microg ml(
      1) with a relative standard deviation (RSD) of 6.2%; cumene was not detected. The
      factors influencing SPE e.g., adsorbent types, sample load volume, eluting
      solvent, headspace and temperatures, were investigated. A cartridge containing a
      C18 adsorbent and using dichloromethane gave a better performance for the
      extraction of BTEXC from water. Average recoveries exceeding 90% could be
      achieved for cumene at 4 degrees C with a 2.7% RSD.

PMID- 14596401
TI  - Temperature effect on the selective hydration of sodium ion in nitrobenzene.
AB  - The effect of the temperature on the co-extraction of water molecules with Na+
      from water to nitrobenzene (NB) in the presence of dipicrylaminate ion has been
      studied. The number (n) of water molecules co-extracted with a Na+ ion, as
      measured by the Karl Fischer method, increased from 3.1 to 5.2 with increasing
      temperature (6-65 degrees C). This observation is in apparent contradiction to
      the expectation from simple thermodynamics because hydration is generally an
      entropically unfavorable process. Additional 1H NMR experiments for the selective
      hydration of Na+ in deuterated NB have confirmed that the association constants
      of water with Na+ indeed decrease with increasing temperature. On the other hand,
      however, it has been shown that water solubility into NB substantially increases
      with temperature. We conclude that the latter effect overwhelms the former
      unfavorable entropy effect, which results in a net increase of the n-value, as
      observed.

PMID- 14596402
TI  - Reversible and irreversible adsorption of surfactants at a hanging mercury drop
      electrode.
AB  - The adsorption-desorption phenomena of surfactants were studied by measuring
      differential capacity-potential curves in a static solution and differential
      capacity-time curves in a flowing solution. The surfactants investigated were
      Aerosol OT, cetylpyridinium chloride, Hyamin 1622, tetrabutylammonium bromide,
      Triton X-100 and trioctylphosphineoxide. The differential capacity-potential and
      differential capacity-time curves for these surfactants showed different shapes,
      with and without peaks. The differential capacity-time curves were used to study
      the adsorption reversibility of the surfactants at a mercury electrode. The
      adsorptions of Hyamin 1622 and Triton X-100 were irreversible at all the
      potentials investigated. The adsorptions of Aerosol OT and trioctylphosphineoxide
      were irreversible except at the potential more positive than -0.2 V. The
      adsorption of tetrabutylammonium bromide was almost reversible at any potential
      investigated. The adsorption of cetylpyridinium chloride was complicated,
      indicating different orientations of adsorption.

PMID- 14596403
TI  - Novel imidazole PVC-based sensor based on a thiopyrilium compound.
AB  - A novel imidazole membrane sensor based on 2,4,6-triphenyl thiopyrilium
      perchlorate (TTP) as an excellent charged carrier, poly(vinyl chloride) (PVC),
      the plasticizer dibutyl phthalate (DBP) and oleic acid as an additive is
      described. The sensor responds to imidazole over a wide concentration range from
      1.0 x 10(-5) to 1.0 x 10(-1) M with a slope of +33.5 +/- 0.5 mV per decade. The
      detection limit of the electrode is 3.0 x 10(-6) M and it can be used for at
      least four weeks without any measurable change in sensitivity. The sensitivity of
      the electrode is high enough to permit the detection of as little as 0.2
      microg/ml of imidazole without any significant interference from high levels of
      other components and especially, amino acids. The potentiometric selectivity
      coefficient data revealed negligible interference from common cations, anions and
      amino acids. The electrode has a relatively fast response time (<30 s), and good
      slope stability. The proposed sensor was successfully applied to the
      determination of imidazole in synthetic serum samples.

PMID- 14596404
TI  - A new type of chemically bonded phase for reversed-phase HPLC.
AB  - A new type of ether-bonded packing for reversed-phase HPLC (RP-HPLC) was
      synthesized by reacting 1-octanol with beta-(3,4
      epoxycyclohexyl)ethyltrimethoxysilane, followed by coupling the product onto
      porous silica. The prepared packing was characterized by elemental analysis,
      solid-state 13C NMR, and Fourier transform infrared (FT-IR) spectroscopy.
      Chromatographic evaluations were performed by using a mixture of organic
      compounds as the analyte and methanol-water as binary mobile phase. The influence
      of the composition of organic modifier on the retention behavior of basic
      compounds was studied. The hydrolytic stability of the packing between pH 2.5-7.5
      was also investigated. The results showed that the new stationary phase has
      excellent chromatographic properties and good hydrolytic stability.

PMID- 14596405
TI  - The quality assessment of compound liquorice tablets by capillary electrophoresis
      fingerprints.
AB  - Capillary electrophoresis (CE) is a powerful separation technique that is
      peculiarly able to determine the fingerprints of traditional Chinese medicine.
      The Capillary Electrophoresis Fingerprints (CEFP) of compound liquorice tablets
      (CLTs) was established to evaluate the quality of CLTs. The background
      electrolyte was a 50 mM sodium borate solution. The detection wavelength was 228
      nm and a 14 kV voltage was applied. Hydrochlorothiazide served as an internal
      standard and temperature was 24-25 degrees C. The CLTs were extracted by a 50 mM
      borate solution containing 10% (v/v) methanol. The results showed that CE was a
      powerful tool for detecting of the fingerprints of traditional Chinese medicine
      and their constituents. The quality assessments were performed to compare the
      correlation coefficients (R) and cos theta (C) between each batch vector of CLTs
      and the total standard profile vector (TSPV), which was the mean vector of all
      the batch vectors of CLTs with 1.0. The nearer to 1.0 was the R or C, the higher
      was the similarity. The values of R and C between the TSPV and each batch vector
      of CLTs produced at different factories were all above 0.9150. The values of R
      and C between every two standard profile vectors (SPV) from different factories
      were all above 0.9420. A good stability and reproducibility of the CEFP of CLTs
      were obtained in the study. Further, we first put forward a new parameter Q to
      evaluate both the quantification accuracy and the qualitative accuracy for a
      CEFP, which was verified by determinations of GHIA, GHEA, MP and SB in CLTs. The
      CEFP was successfully employed to assess the quality of CLTs produced at Kunming
      Pharmaceutical Factory to be good.

PMID- 14596406
TI  - Flotation-separation of aluminum from some water samples using powdered marble
      waste and oleic acid.
AB  - Bench-scale experiments were conducted in the laboratory, aiming to remove
      aluminum from water. They were based on the use of powdered marble wastes (PMW),
      which are inexpensive and produced in large quantity, and thus potentially cause
      environmental problems, as an effective inorganic sorbent and oleic acid (HOL) as
      surfactant. The main parameters (solution pHs, sorbent, surfactant and aluminum
      concentrations, shaking time, ionic strength and the presence of foreign ions)
      that influence the sorptive-flotation process were examined. Good results were
      obtained under the optimum conditions, for which nearly 100% of aluminum at pH 7
      and at room temperature (approximately 25 degrees C) was removed. The procedure
      was successfully applied to the recovery of aluminum spiked to some natural water
      samples. Moreover, a sorption and flotation mechanism is suggested.

PMID- 14596407
TI  - Separation and determination of methyl tert-butyl ether and its degradation
      products by a laboratory-constructed micro-cryogenic chromatographic oven.
AB  - A laboratory-made micro-cryogenic chromatographic oven was mainly improved in
      size, which was controlled at 6 x 6 x 2.5 cm. A thermoelectric system was used to
      cool the capillary column instead of the traditional liquid cryogen. A cold block
      connected to the cryogenic module was directly solidified at room temperature
      with thermally conductive adhesive so that the uniformity of transferring heat
      was greatly improved, and the size of the system was reduced. Moreover, this
      system was inexpensive and convenient for both operation and control. The newly
      developed device coupled with headspace solid-phase microextraction (SPME) was
      successfully applied to the determination of methyl tert-butyl ether (MTBE) and
      its degradation products. During the analysis procedure, a 65 microm
      polydimethylsiloxane/divinylbenzene (PDMS/DVB) fiber was used to extract MTBE and
      its degradation products. The extraction was controlled at 50 degrees C for 30
      min and the NaCl content in the sample was maintained at 35%. The limits of
      detection (LODs) ranged from 0.006 microg mL(-1) (for MTBE) to 0.206 microg mL(
      1) (for methyl acetate) and the relative standard deviations (RSD%) were below
      4%. The spiked recoveries for the developed method were evaluated using various
      water samples as a matrix.

PMID- 14596408
TI  - Analysis of lead in tooth enamel by laser ablation-inductively coupled plasma
      mass spectrometry.
AB  - Laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) was used
      to determine the Pb/Ca ratios in the enamel of deciduous incisors, a biomarker of
      in utero Pb exposure, using pelletized bone certified reference materials (CRMs)
      as calibrants. The detection limit for Pb by LA-ICP-MS was 11 microg kg(-1)
      demonstrating an adequate sensitivity for Pb in the teeth of unexposed
      individuals (0.1-10 mg kg(-1)). The precision for the Pb/Ca ratios in NIST SRM
      1486 Bone Meal was 3.4%. The correlation between Pb/Ca ratios obtained by LA-ICP
      MS and those obtained by a digestion method was highly significant. We found one
      point calibration by a CRM was applicable for the quantification of Pb in tooth
      enamel. This method will be valuable for the assessment of in utero Pb exposure
      levels.

PMID- 14596409
TI  - Adsorption behavior of noble metal ions (Au, Ag, Pd) on nanometer-size titanium
      dioxide with ICP-AES.
AB  - The adsorption behavior of gold (Au), silver (Ag) and palladium (Pd) on nanometer
      size titanium dioxide (NSTD) at low concentrations was studied using inductively
      coupled plasma atomic emission spectrometry (ICP-AES). A preconcentration
      procedure of the analytes was carried out using NSTD as a solid-phase extractant
      before their determination by ICP-AES. The optimum conditions for adsorption were
      studied in detail, and under the condition that Au, Ag and Pd ions could be
      adsorbed and recovered quantitatively. The static adsorption capacities of Au, Ag
      and Pd on NSTD were 22.63, 14.06 and 11.82 mg/g, respectively. For the elution of
      gold, silver and palladium, a mixture of 5% thiourea solution and 3 mol L(-1)
      HNO3 was used. The parameters tested included: pH conditions, contact time of the
      analytes with NSTD, flow rate, adsorption capacity and sorption kinetics.
      According to the definition of IUPAC, the detection limits (3sigma) of this
      method for Au, Ag and Pd with an enrichment factor of 50 were (0.016), (0.006)
      and (0.012) microg mL(-1), respectively, the relative standard deviations (RSD)
      were 8.7%, 4.5% and 7.4%, respectively (n = 6). Some geological samples were
      determined with satisfactory results.

PMID- 14596410
TI  - Theoretical analysis of gold-deposited optical fiber sensor and characterization
      of the gold film.
AB  - Gold-deposited optical fiber sensors with film thicknesses from 30 to 60 nm were
      prepared, and the responses to a wide range of a refractivity (1.33-1.54
      refractive index (RI) units) were investigated both experimentally and
      theoretically. The response curve of the sensor has two minima in the
      refractivity range from 1.33 to 1.44 and at 1.462 RI units. The former minimum is
      due to surface plasmon resonance (SPR) in the thin gold film, and shifts to a
      lower refractivity as the film becomes thicker. The response curves of the
      sensors with film thicknesses of 45 and 60 nm agreed well with those calculated
      from SPR theoretical equations. Morphology observations of the surfaces of
      deposited gold films on glass by atomic force microscopy (AFM) and a variation in
      resistance of the films with various thicknesses show the structure of the gold
      films. We concluded that the thin deposited gold films have many defects, and
      that the core of the gold-deposited optical fiber leaks light through the defects
      to the sample solution with the same refractivity (1.462 RI units) as that of the
      core.

PMID- 14596411
TI  - Simple and rapid determination of trace amounts of gold(III), palladium(II), and
      platinum(IV) in industrial waste solutions after recovery of noble metals by
      combined use of GFAAS and anion-exchange separation.
AB  - A simple and rapid method for the analysis of trace amounts of gold(III),
      palladium(II), and platinum(IV) by the combined use of graphite furnace atomic
      absorption spectrometry and anion-exchange separation was proposed, and
      successfully applied to the rapid determination of metals in industrial waste
      solutions obtained from the final process of noble-metal recovery factories,
      because noble metals can be selectively and quantitatively separated to a high
      degree by using a small column containing only a 0.7 g-portion of a common anion
      exchange resin and a dilute thiourea solution.

PMID- 14596412
TI  - Data analysis in the determination of stoichiometries and stability constants of
      complexes.
AB  - The determination of stoichiometries and stability constants of complexes by
      means of UV-visible spectrophotometry applying traditional methods does not
      evaluate the quality of the values obtained, since the classic application of
      these methods does not provide coverage intervals. However, the use of
      chemometric techniques in different steps of the application of these methods
      makes it possible to obtain not only a real value of the characteristics of the
      complexes but a validation of such a value. In this paper a methodology is
      proposed that combines some traditional methods, three different regression
      models (LMSR, LSR and LSPR) and a small number of mathematical algorithms. This
      methodology is able to estimate, in a simple and rigorous way, the stoichiometry
      and stability constant of a complex and its corresponding uncertainties.

PMID- 14596414
TI  - A new water-soluble chromogenic indicator: an application to the determination of
      chlorine in aqueous solutions.
AB  - A novel compound, N,N'-bis(2,4-di-sulfobenzyl)tolidine tetrasodium salt (SBT),
      was synthesized for use as a chromogenic indicator for oxidizing substances, and
      its applicability to the colorimetric determination of chlorine in water was
      examined.

PMID- 14596413
TI  - Segment identification of a ligand binding with a protein receptor using
      multidimensional T1rho-, diffusion-filtered and diffusion-ordered NOESY
      experiments.
AB  - Multidimensional T1rho-, diffusion-filtered and diffusion-ordered NOESY
      techniques were applied to identify segments of a ligand binding with a protein
      receptor. These experiments can easily provide intermolecular NOEs of the
      complex, which are of great significance for characterizing the binding epitopes
      of a ligand. This information cannot be obtained by high-throughput 1D NMR
      experiments, used for determining the binding affinity, although multidimensional
      NMR experiments require more experiment time. The present results indicate that
      the current experiments using T1rho- and diffusion-edited techniques are very
      suitable for identifying segments of a ligand binding with a protein receptor in
      the drug discovery process.

PMID- 14596415
TI  - Determination of nickel with 2-(2-quinolylazo)-5-diethylaminoaniline as a
      chromogenic reagent.
AB  - A sensitive, selective and rapid method for the determination of nickel based on
      a rapid reaction of nickel(II) with 2-(2-quinolylazo)-5-diethylaminoaniline
      (QADEAA) has been developed. In the presence of pH = 6.0 ammonia-ammonium
      chloride buffer solution and sodium dodecyl sulfonate (SDS) medium, QADEAA reacts
      with nickel to form a violet complex having a molar ratio of 1:2 (nickel to
      QADEAA). The molar absorptivity of the complex is 1.38 x 10(5) l mol(-1) cm(-1)
      at 595 nm. Beer's law is obeyed in the range of 0.01-0.4 microg/ml. This method
      had been applied to the determination of nickel with good results.

PMID- 14596416
TI  - Preconcentration and speciation of chromium in water samples by atomic absorption
      spectrometry after cloud-point extraction.
AB  - A rapid, sensitive and accurate atomic absorption method for Cr(III) and Cr(VI)
      ions was developed based on the cloud-point extraction (CPE) technique. Cr(III)
      reacts with a new Schiff's base ligand to form the hydrophobic complex, which is
      subsequently entrapped in the surfactant micelles. The Cr(VI) assay is based on
      its reduction to Cr(III) by the addition of concentrated H2SO4 and ethanol to the
      sample solution. The condensed surfactant phase containing the metal chelates is
      introduced into an atomic absorption spectrometer. The relative standard
      deviations were 2.1% for both species and the limits of detection were around
      0.17 microg l(-1).

PMID- 14596417
TI  - Colorimetric determination of benzocaine, lignocaine and procaine hydrochlorides
      in pure form and in pharmaceutical formulations using p-benzoquinone.
AB  - A simple, accurate and sensitive method for the microdetermination of benzocaine,
      lignocaine and procaine hydrochlorides in pure forms and in pharmaceutical
      formulations is described. The procedure is based on the reaction of those drugs
      in an aqueous acidic medium with p-benzoquinone to form charge-transfer
      complexes. The method has been used for the determination of 5.0-70, 5.0-60 and
      5.0-90 microg ml(-1) of benzocaine, lignocaine HCl and procaine HCl,
      respectively. The complexes have apparent molar absorptivities of 1.70 x 10(3),
      2.79 x 10(3) and 2.42 x 10(3) L mol(-1) cm(-1) and Sandell sensitivities of 9.72,
      10.34 and 11.25 ng cm(-2), respectively. The proposed procedure of analysis is as
      accurate as the British Pharmacopoeial method (2003). The method was successfully
      used for the determination of those drugs in the presence of their degradation
      products, additives and excipients, which were normally encountered in
      pharmaceutical formulations.

PMID- 14596418
TI  - Crystal structure of 6-oxa-3,9-dithiabicyclo[9.2.2]pentadeca-1(15),11,13-triene.
AB  - The structure of an S2O mixed-donor macrocycle incorporating para-substituted
      xylyl subunit was characterized by a single crystal X-ray analysis. The crystal
      structure shows an exo-dentate orientation of sulfur and oxygen donor atoms due
      to the fully stretched aliphatic ring conformation. Thus all of torsional angles
      between donor atoms are arranged anti and S...S distance in a ring is 6.764(1)A,
      which is larger than those values of ortho- and meta-type analogs. The observed
      high rigidity of the ring conformation may induce the extraordinary behaviors in
      chelation.

PMID- 14596419
TI  - Crystal structure of 12-methoxy-8,8,21,21-tetramethyl-5-(3-methylbut-2,4-dienyl)
      19-(3-methylpent-4-enyl)-3,7,20
      trioxahexacyclo[15.4.1.0<2,15>.0<2,19>.0<4,13>.0<6,11>]docosa-4(13),5,9,11,15
      pentaene-14,18-dione.
AB  - The title compound was extracted from the natural product of plant origin. It
      crystallizes in tetragonal space group P4(1) or P4(3), with cell parameters a =
      15.795(2)A, c = 11.970(5)A and Z = 4. The structure exhibits intermolecular
      hydrogen bonds of the type C-H...O.

PMID- 14596420
TI  - Congenital heart block: do fetal factors fuel the fire from inflammation to
      fibrosis?

PMID- 14596421
TI  - Familial autoimmunity as a risk factor for systemic lupus erythematosus and vice
      versa: a case-control study.
AB  - The objective of this multicentric case-control study was to investigate if a
      history of autoimmune disease (AD) in first-degree relatives (FDR) is a risk
      factor for systemic lupus erythematosus (SLE) and to evaluate the risk of AD
      among FDR of SLE patients. Cases were Italian SLE patients consecutively
      enrolled. Controls were orthopaedic inpatients without any autoimmune diseases.
      The strength of the association between family history of AD and SLE was measured
      as an odds ratio (OR) calculated from the coefficient of an unconditional
      regression model. To calculate the risk of AD among FDR of SLE patients, the
      extended generalized estimating equation technique was used. In total, 154 SLE
      cases and 140 controls were enrolled. A family history of AD was reported by
      22.7% of SLE patients and by 5.7% of the controls. The risk of SLE increased with
      the number of FDR with AD (one FDR affected, OR = 4.1; two or more, OR = 11.3).
      The probability of having AD was higher among FDR of SLE cases in comparison to
      FDR of controls (RR = 4.6; 95%CI 1.9-11.1). A female SLE patient conferred an
      increased risk of AD to her FDR; this risk is doubled in females (OR 10.3; 95% CI
      3.1-34.4).

PMID- 14596422
TI  - Thromboembolism in paediatric lupus patients.
AB  - Paediatric patients with systemic lupus erythematosus (SLE) and antiphospholipid
      antibodies (aPL), specifically lupus anticoagulants (LAC) are at high risk of
      developing thromboembolic events (TE). Our objectives were to determine the
      prevalence of TE in paediatric SLE patients with LAC and to determine if
      anticoagulation was effective to decrease morbidity, and prevent recurrent TE. We
      reviewed data on 149 paediatric SLE patients treated over 10 years. In all, 24
      patients (16%) were LAC positive, and 21 TE occurred in 13 of these LAC positive
      patients (54% incidence of TE in LAC positive patients). The events were cerebral
      venous thrombosis (9), arterial stroke (3), deep venous thrombosis (4), pulmonary
      embolism (2), other venous event (1) and other arterial events (2). The median
      duration between SLE diagnosis and first TE was 15.2 months (range 0-62), and the
      median age at first TE was 15.1 years (range 11.4-18.4). Long-term
      anticoagulation was prescribed, and eight patients (62%) were transferred to
      adult care on lifelong oral warfarin; four (31%) remain under our care on
      lifelong warfarin, and one patient died of causes unrelated to her TE. No patient
      has been identified with deficiencies of protein C, protein S or antithrombin
      III. One patient is heterozygous for Factor V Leiden, and one is heterozygous for
      both the Prothrombin 20210A mutation and the MTHFR (methylene tetrahydrofolate
      reductase) mutation. Four patients had recurrent TE (31%), and three were not
      anticoagulated at the time of their second event. One patient had two recurrences
      on therapeutic anticoagulation. Thromboembolic events are prevalent in the LAC
      positive paediatric SLE population, and consideration for lifelong
      anticoagulation must occur after an initial TE.

PMID- 14596423
TI  - Anticardiolipin antibodies in various diseases in Taiwan: a retrospective
      analysis.
AB  - The goals of this study are to determine the frequency of anticardiolipin
      antibodies (ACA) in patients with various diseases and to evaluate the clinical
      significance of ACA in Taiwan. We collected 690 patients from ACA laboratory
      records. They were divided into eight groups in order to compare ACA percentages.
      Positive rates of ACA in different disease groups were below 20%, except for
      38.2% in autoimmune diseases with vascular thrombosis. Compared with old stroke,
      the ACA positivity in young stroke was not significantly different (P = 0.482).
      The positive percentage of lupus anticoagulant (LA) (2.86%) was lower than that
      of ACA (15.66%) in young stroke (P = 0.015). Among patients with pregnancy loss
      or prematurity, the ACA positivity in lupus patients (44.44%) was higher than
      without lupus (9.76%; P = 0.01). The prevalence of ACA is higher in patients with
      vascular thrombosis complicated by autoimmune diseases than with thrombosis alone
      in Taiwan. Young and old stroke do not differ in ACA positivity. Moreover, ACA is
      more prevalent than LA for young stroke related coagulation. The ACA positivity
      for pregnancy loss or prematurity is very low in Taiwan. In summary, this is the
      first report on the frequency of ACA and other coagulation factors in various
      diseases in Taiwan.

PMID- 14596424
TI  - Assessment of strategies for identifying diagnosed cases of systemic lupus
      erythematosus through self-report.
AB  - The objective of this work was to assess the optimal way to identify potential
      systemic lupus erythematosus (SLE) cases in large epidemiologic studies through
      self-reported information about diagnosis of SLE, symptoms and medications, and
      to investigate the utility of a criteria checklist sent directly to participants'
      physicians. We used data collected in 1997 from 53322 participants in a study of
      African-American women, the Black Women's Health Study, including a lupus
      screening questionnaire (LSQ) and questions about SLE diagnosis and medications.
      We confirmed self-reported SLE through medical records and criteria checklists
      sent to participants' physicians. Among those for whom we received medical
      records and/or criteria checklists, we compared the predictive value and
      proportion of missed cases of several algorithms using combinations of self
      reported SLE diagnosis, LSQ score and medication use to self-reported SLE
      diagnosis alone. We obtained a physician checklist or medical chart for 251
      individuals who reported SLE, of whom 212 (84%) fulfilled ACR criteria for
      definite or probable SLE, or had clinical lupus (SLE diagnosis recorded in
      medical charts plus appropriate medication use). The use of LSQ score or
      medication use in addition to self-report of SLE tended to decrease the false
      positive rate but also to reduce the proportion of true cases identified.
      Checklists of ACR criteria completed by subjects' physicians documented more
      criteria than medical records. In conclusion, among participants who consented to
      medical record review, SLE prediction algorithms using questions about lupus
      symptoms and medications offered slightly higher predictive value for detecting
      cases than self-reported diagnosis alone, but at the cost of case detection. SLE
      case confirmation strategies can be complemented by the use of criteria
      checklists sent directly to participants' physicians.

PMID- 14596425
TI  - Renal involvement in primary antiphospholipid syndrome and its response to
      immunosuppressive therapy.
AB  - Antiphospholipid syndrome (APS) is the association between antiphospholipid
      antibodies, venous and arterial thrombosis and pregnancy morbidity. Although the
      kidney may be affected in APS, the treatment of renal involvement is yet to be
      elucidated. This report describes the clinical and laboratory features of four
      patients with primary APS nephropathy, and the beneficial effect of
      immunosuppressive therapy accompanied by warfarin and angiotensin-converting
      enzyme inhibitor. We also briefly discuss the possible mechanisms of the
      beneficial effects of immunosuppressives on primary APS nephropathy.

PMID- 14596426
TI  - Abnormal expression of chemokine receptors on T-cells from patients with systemic
      lupus erythematosus.
AB  - The expression of chemokine receptors on T-cells and chemokine levels in the
      blood was studied in 23 patients with SLE (ACR criteria), seven patients with
      rheumatoid arthritis (RA) and in 15 healthy controls using flow cytometry, RT-PCR
      and ELISA. The cell surface expression of the chemokine receptors CXCR5 and CCR6
      was decreased in SLE patients compared with controls (P = 0.051 and P = 0.002,
      respectively). The decrease of CXCR5 was confined to SLE patients with inactive
      disease (SLEDAI < 6) compared with active disease (SLEDAI > 6) and controls.
      CXCR2 and CCR1 were increased in patients with active SLE compared with patients
      with inactive disease (P = 0.001 and P = 0.01, respectively) and with controls (P
      = 0.02 and P = 0.053, respectively). The levels of the chemokines MIP-1alpha MCP
      1, SDF-1alpha, IP-10 and RANTES were significantly elevated in SLE patients
      compared with controls. Patients with renal involvement had increased surface
      expression of CXCR3 and CCR3 (P = 0.04 in both) and a lower level of soluble IP
      10 compared with patients without renal disease (P = 0.025) and compared with
      controls (P = 0.001). The ratio between CCR5 and CCR3 was significantly increased
      in RA patients compared with SLE patients and controls supporting a Th1
      overweight in RA. In conclusion, patients with SLE showed abnormal T-cell
      expression of several chemokine receptors and levels of soluble chemokines in
      their plasma/serum.

PMID- 14596428
TI  - Successful long-term treatment of systemic lupus erythematosus with rituximab
      maintenance therapy.
AB  - Systemic lupus erythematosus (SLE) is a chronic, inflammatory autoimmune disease
      that may involve multiple organ systems. Treatment consists of immunosuppression,
      cytotoxic treatment, plasmapheresis and immunoglobuline therapy. Treatment of
      patients refractory to standard treatment approaches is difficult and results are
      poor. We describe a 39-year old patient with SLE suffering from grand mal
      epilepsy due to cerebral vasculopathy with positive lupus anticoagulant, who was
      refractory to standard treatment modalities. The patient was treated with the
      anti-CD20 monoclonal antibody rituximab (375 mg/m2 x 4, repeated at weekly
      intervals). Rituximab applications were delivered in October 2000, March 2001 and
      October 2001. Since March 2002 she has received maintenance therapy with
      rituximab 375 mg/m2 every three months. A second female with refractory SLE was
      treated successfully in April 2002 and receives maintenance therapy every three
      months. Both patients responded well to rituximab therapy. The first patient
      showed a major improvement of her clinical condition, and 30 months after the
      beginning of the rituximab therapy she is free of any symptoms. Inflammation
      parameters, ANA and lupus anticoagulant declined significantly after the
      treatment. The clinical condition of the second patient improved dramatically,
      all inflammation parameters normalized and her circulating immunocomplexes
      disappeared. In conclusion, rituximab maintenance treatment may be a new
      effective therapy in SLE.

PMID- 14596427
TI  - Neonatal lupus: fetal myocarditis progressing to atrioventricular block in
      triplets.
AB  - We report a case of neonatal lupus syndrome (NLS) in an in vitro fertilization
      induced triplet pregnancy. Echocardiographic signs of myocarditis were evident at
      the 21st week of gestation (w.g.) in twin I, with a subsequent development of a
      complete atrioventricular (AV) block at the 25th w.g.; twin III also displayed
      echocardiographic signs of myocarditis at the same time. Treatment with
      dexamethasone (4mg/day) was started at the 25th w.g. A complete echocardiographic
      regression of the myocarditis signs was achieved, while AV block was unaffected.
      Caesarian section was performed at the 31.5 w.g. after a premature rupture of the
      membranes. Complete AV block was confirmed in twin I with a heart rate of 51
      beats/min that required a pacemaker implant 40 days after. Twin III developed a
      first-degree AV block that switched to a periodic second-degree block later,
      while twin II displayed only liver enzyme abnormalities.

PMID- 14596429
TI  - Remission of refractory lupus nephritis with a protocol including rituximab.
AB  - Immunosuppression with corticosteroids and cyclophosphamide is the standard of
      care for lupus nephritis. We report a 19-year old woman with lupus nephritis and
      nephrotic syndrome who had not achieved complete remission after treatment with
      15.7 g cyclophosphamide and 13.7 g prednisone. We planned a consolidation phase
      with: 1) cyclophosphamide 20 mg/kg i.v. every 28 days for three cycles; 2) anti
      CD20 chimeric monoclonal antibody (rituximab) 375 mg/m2 i.v. weekly for four
      weeks; and 3) slow tapering of prednisone p.o., q.o.d., after a reinduction dose
      during rituximab administration. At the end of this phase the patient achieved
      complete remission. An indefinite maintenance treatment with methotrexate,
      cyclosporin and low-dose prednisone was then started. Twenty-four months later
      the patient remains in remission. In the immunosuppressive treatment of lupus
      nephritis the insertion of a consolidation phase with rituximab combined with
      cyclophosphamide achieves a therapeutically important and lasting deletion of the
      lymphocyte clone responsible for autoimmunity.

PMID- 14596430
TI  - Rate, pattern and factors related to damage in Brazilian systemic lupus
      erythematosus patients.
AB  - The Systemic Lupus International Collaborating Clinics/American College of
      Rheumatology (ACR) Damage Index (SDI) is an accepted instrument to ascertain
      damage. It has been shown to vary among different SLE populations. The aim of
      this study was to assess SDI score, pattern and factors related to damage in
      Brazilian SLE outpatients. The SDI was obtained in 105 patients with a median age
      of 41 (5-95%, 19-61.7) years and a median SLE duration of 127 (17.6-345.9)
      months. Patients had a median SDI of 2 (0-8) and 81.9% had some damage (SDI > 0).
      Damage was associated with a higher number of ACR criteria for SLE in
      multivariate analysis (OR = 2.32, 95%CI = 1.23-4.37, P = 0.009). Antiphospholipid
      syndrome (APS) (OR = 9.82, 95%CI = 2.74-35.23, P < 0.001), methylprednisolone
      pulses (OR = 3.91, 95%CI = 1.19-12.81, P = 0.024), age (OR = 1.70, 95%CI = 1.02
      1.13, P = 0.011) and prednisone use duration (OR = 1.01, 95%CI = 1.002-1.02, P =
      0.020) were related to severe damage (SDI > or = 4). Hypertension was associated
      with renal, cardiac and atherosclerotic damage, as cyclophosphamide pulses were
      with premature menopause. In conclusion, damage was very frequent in Brazilian
      SLE patients, mainly due to skin involvement, compared to other SLE populations.
      The presence of APS was the major independent contributor to the development of
      severe damage. Arterial hypertension was identified as a common risk factor for
      renal, cardiac and atherosclerotic damage.

PMID- 14596431
TI  - C1q autoantibodies: cause or effect of recurrent infection.

PMID- 14596432
TI  - Successful treatment with anti-CD20 monoclonal antibody (rituximab) of life
      threatening refractory systemic lupus erythematosus with renal and central
      nervous system involvement.

PMID- 14596433
TI  - The U.S. primary care physician workforce: minimal growth 1980-1999.
AB  - Growth in the primary care physician workforce (physicians per capita) in the
      United States has trailed the growth of the specialist physician population in
      recent years. This has occurred despite calls during the same period for
      increased production of primary care physicians and educational reforms focusing
      on primary care.

PMID- 14596434
TI  - The U.S. primary care physician workforce: persistently declining interest in
      primary care medical specialties.
AB  - A persistent, six-year trend in the choice of specialty training by U.S. medical
      students threatens the adequacy of the physician workforce of the United States.
      This pattern should be reversed and requires the attention of policy makers and
      medical educators.

PMID- 14596435
TI  - The U.S. primary care physician workforce: undervalued service.
AB  - Primary care physicians work hard, but their compensation is not correlated to
      their work effort when compared with physicians in other specialties. This
      disparity contributes to student disinterest in primary care specialties.

PMID- 14596436
TI  - Hormone therapy to prevent hip fractures in elderly.

PMID- 14596437
TI  - Why does a U.S. primary care physician workforce crisis matter?

PMID- 14596438
TI  - Strategies to improve diabetes care.

PMID- 14596439
TI  - Common stress fractures.
AB  - Lower extremity stress fractures are common injuries most often associated with
      participation in sports involving running, jumping, or repetitive stress. The
      initial diagnosis can be made by identifying localized bone pain that increases
      with weight bearing or repetitive use. Plain film radiographs are frequently
      unrevealing. Confirmation of a stress fracture is best made using triple phase
      nuclear medicine bone scan or magnetic resonance imaging. Prevention of stress
      fractures is most effectively accomplished by increasing the level of exercise
      slowly, adequately warming up and stretching before exercise, and using cushioned
      insoles and appropriate footwear. Treatment involves rest of the injured bone,
      followed by a gradual return to the sport once free of pain. Recent evidence
      supports the use of air splinting to reduce pain and decrease the time until
      return to full participation or intensity of exercise.

PMID- 14596440
TI  - Panax ginseng.
AB  - The herbal remedies referred to as "ginseng" are derived from the roots of
      several plants. One of the most commonly used and researched of the ginsengs is
      Panax ginseng, also called Asian or Korean ginseng. The main active components of
      Panax ginseng are ginsenosides, which have been shown to have a variety of
      beneficial effects, including anti-inflammatory, antioxidant, and anticancer
      effects. Results of clinical research studies demonstrate that Panax ginseng may
      improve psychologic function, immune function, and conditions associated with
      diabetes. Overall, Panax ginseng appears to be well tolerated, although caution
      is advised about concomitant use with some pharmaceuticals, such as warfarin,
      oral hypoglycemic agents, insulin, and phenelzine. Panax ginseng does not appear
      to enhance physical performance. Products with a standardized ginsenoside
      concentration are available.

PMID- 14596441
TI  - Tremor.
AB  - Tremor, a rhythmic, involuntary, oscillatory movement of body parts, is the most
      common movement disorder. Tremors are classified as rest or action tremors. Rest
      tremor occurs when the affected body part is completely supported against
      gravity. Action tremors are produced by voluntary muscle contraction and are
      further divided into postural, isometric, or kinetic tremors. This article
      describes clinical signs and symptoms of six tremor syndromes, including
      physiologic tremor, essential tremor, Parkinson's disease, toxic and drug-induced
      tremor, cerebellar tremor, and psychogenic tremor, and presents a detailed
      diagnostic approach to tremor. Although new technologies such as positron
      emission tomography and single photon emission computed tomography are under
      investigation for possible use in diagnosing specific tremor syndromes, they have
      no widespread applicability or use at this time. The history and physical
      examination remain the most important diagnostic tools available to clinicians in
      identifying and classifying tremor syndromes.

PMID- 14596442
TI  - Information from your family doctor. Essential tremor.

PMID- 14596444
TI  - Information from your family doctor. What to do when your child refuses to go to
      school.

PMID- 14596443
TI  - School refusal in children and adolescents.
AB  - School refusal is a problem that is stressful for children, families, and school
      personnel. Failing to attend school has significant short- and long-term effects
      on children's social, emotional, and educational development. School refusal
      often is associated with comorbid psychiatric disorders such as anxiety and
      depression. It is important to identify problems early and provide appropriate
      interventions to prevent further difficulties. Assessment and management of
      school refusal require a collaborative approach that includes the family
      physician, school staff, parents, and a mental health professional. Because
      children often present with physical symptoms, evaluation by a physician is
      important to rule out any underlying medical problems. Treatments include
      educational-support therapy, cognitive behavior therapy, parent-teacher
      interventions, and pharmacotherapy. Family physicians may provide
      psychoeducational support for the child and parents, monitor medications, and
      help with referral to more intensive psychotherapy.

PMID- 14596445
TI  - Reducing cardiovascular disease risk in patients with type 2 diabetes: a message
      from the National Diabetes Education Program.
AB  - Cardiovascular disease is responsible for 65 percent of deaths in persons with
      type 2 diabetes. However, awareness of cardiovascular disease risk factors among
      patients with diabetes remains low, resulting in missed opportunities to lower
      risks for coronary events and strokes. The National Diabetes Education Program
      has begun a campaign to increase patient participation in risk-reduction practice
      s by promoting the "ABCs" of diabetes care: A(1c) level, Blood pressure, and
      Cholesterol level. By increasing patient awareness of the link between diabetes
      and heart disease, family physicians can encourage patients to take medications
      (including aspirin), stop smoking, lower blood pressure, and lower cholesterol
      and blood glucose levels.

PMID- 14596446
TI  - Information from your family doctor. Diabetes and heart disease.

PMID- 14596447
TI  - Repair of obstetric perineal lacerations.
AB  - Family physicians who deliver babies must frequently repair perineal lacerations
      after episiotomy or spontaneous obstetric tears. Effective repair requires a
      knowledge of perineal anatomy and surgical technique. Perineal lacerations are
      classified according to their depth. Sequelae of obstetric lacerations include
      chronic perineal pain, dyspareunia, urinary incontinence, and fecal incontinence.
      With lacerations involving the anal sphincter complex, particular attention must
      be given to anatomy and surgical technique because of the high incidence of poor
      functional outcomes after repair. An overlapping technique to repair the external
      anal sphincter, rather than the traditional end-to-end technique, is being
      investigated to determine if it might decrease the incidence of anal
      incontinence. Minimizing the use of episiotomy and forceps deliveries can
      decrease the occurrence of severe perineal lacerations.

PMID- 14596448
TI  - Ezetimibe for hypercholesterolemia.
AB  - Ezetimibe (Zetia) is a novel, selective cholesterol absorption inhibitor.
      Ezetimibe blocks the absorption of dietary and biliary cholesterol within the
      brush-border enzyme system of the small intestine. Ezetimibe does not appear to
      alter or decrease the absorption of bile acids, fatty acids, fat-soluble
      vitamins, or triglycerides. It is labeled for use in the treatment of primary
      hypercholesterolemia, either as monotherapy or in combination with statins. It
      also is labeled for the treatment of homozygous familial hypercholesterolemia in
      conjunction with statins and as adjunctive therapy to diet in the treatment of
      homozygous sitosterolemia (a rare, inherited, plant sterol storage disease).

PMID- 14596451
TI  - Information from your family doctor. Psoriasis.

PMID- 14596450
TI  - Information from your family doctor. Eczema.

PMID- 14596449
TI  - Photo quiz. Fever, leg pain, and a rash.

PMID- 14596452
TI  - Information from your family doctor. Rosacea.

PMID- 14596453
TI  - Information from your family doctor. Seborrheic dermatitis.

PMID- 14596454
TI  - AAP releases policy statement on eye examinations.

PMID- 14596455
TI  - Effects of acetylcysteine and migration of resident eosinophils in an in vitro
      model of mucosal injury and restitution in equine right dorsal colon.
AB  - OBJECTIVES: To evaluate the in vitro protective effects of acetylcysteine and
      response of resident mucosal eosinophils in oxidant-induced injury to tissues of
      right dorsal colon of horses. ANIMALS: 9 adult horses. PROCEDURE:
      Gastrointestinal mucosa was damaged in vitro with 3 mM hypochlorous acid (HOCl),
      with and without prior exposure to 6mM acetylcysteine. Control tissues were not
      exposed to HOCl or acetylcysteine. Control and damaged tissues were incubated in
      Krebs-Ringer-bicarbonate solution and tissue resistance measured during 240
      minutes. Tissue permeability to radiolabeled mannitol was also used to assess
      mucosal barrier integrity. Tissues were examined by light microscopy before and
      after HOCl exposure and during and after incubation. RESULTS: Exposure to HOCl
      caused tissue damage and decreased tissue resistance. Restitution did occur
      during the incubation period. Eosinophils were located near the muscularis
      mucosae in freshly harvested tissues and migrated towards the luminal surface in
      response to HOCl-induced injury. Compared with tissues treated with HOCl without
      acetylcysteine, pretreatment with acetylcysteine prevented HOCl-induced tissue
      damage, changes in resistance, and histologically detectable eosinophil
      migration. The permeability to mannitol increased to the same extent in tissues
      treated with HOCl alone or with acetylcysteine and HOCl. CONCLUSIONS AND CLINICAL
      RELEVANCE: Eosinophils migrated toward the mucosal surface in equine colon in
      response to oxidant-induced damage in vitro. This novel finding could be relevant
      to inflammation in equine colon and a pathophysiologic feature of many colonic
      diseases. Acetylcysteine protected the mucosa against oxidant-induced injury and
      may be useful as a treatment option for various gastrointestinal tract disorders
      in horses.

PMID- 14596456
TI  - Anti-inflammatory effects of intramammary infusions of glycyrrhizin in lactating
      cows with mastitis caused by coagulase-negative staphylococci.
AB  - OBJECTIVE: To determine the anti-inflammatory effects of glycyrrhizin (GL) in
      lactating cows with mastitis attributable to naturally occurring infection with
      coagulase-negative staphylococci (CNS). ANIMALS: 12 lactating Holstein cows with
      mastitis attributable to infection with CNS and 2 healthy cows without mastitis.
      PROCEDURE: Clinical signs, number of bacteria in milk, somatic cell count (SCC)
      in milk, concentrations of alpha-lactalbumin and lactoferrin in milk, and
      concentration of histamine in milk were investigated before and after
      intramammary infusion of GL (6 cows) or antimicrobials (6 cows). Glands of 2
      healthy cows were infused with staphylococcal enterotoxin; milk leukocytes were
      then harvested and incubated with various doses of GL. RESULTS: In cows infected
      with CNS that had a low bacterial concentration in milk, infusion of GL alone
      resulted in significant improvements in swelling, firmness of glands, and number
      of clots in milk, and it decreased the SCC, but not significantly. Percentage of
      neutrophils decreased significantly (to < 30%) by 2 days after infusion. Use of
      lactoferrin as a marker of inflammation in mammary glands revealed a decrease in
      concentrations, whereas use of alpha-lactalbumin as a marker of recovery for
      mammary glands revealed significant increases in concentrations in the GL-infused
      group. Accompanying these anti-inflammatory effects, a decrease in the
      concentration of histamine in milk was observed in the GL-infused group.
      Glycyrrhizin decreased histamine production by milk leukocytes in a concentration
      dependent manner. CONCLUSIONS AND CLINICAL RELEVANCE: Infusion of GL may regulate
      intramammary inflammation through modulation of inflammatory mediators such as
      histamine.

PMID- 14596457
TI  - Evaluation of the safety of ivermectin-praziquantel administered orally to
      pregnant mares.
AB  - OBJECTIVE: To evaluate the safety of an orally administered ivermectin and
      praziquantel paste with regard to variables associated with clinical findings,
      parturition, lactation, maternal care, and neonate viability in pregnant mares.
      ANIMALS: 40 pregnant mares. PROCEDURE: Mares were randomly allocated into
      treatment (n = 20) and control (20) groups and administered a placebo or 3 times
      the therapeutic dosage of ivermectin (0.6 mg/kg) and praziquantel (4.5 mg/kg) at
      14-day intervals until parturition. Physical examinations were performed on mares
      and their foals after parturition (on postpartum days 30, 60, and 90) to identify
      any drug-related effects. As an aid in assessing general health, hematologic and
      serum biochemical analyses were performed monthly on the mares. RESULTS: In blood
      constituents, minor alterations that were not biologically important were
      observed. Reproductive performance was not affected by the unusual treatment
      duration or high dosage, although the drugs were administered during a crucial
      period of equine embryonic development (30 to 60 days). Neither adverse effects
      on mares nor abortions occurred. Follow-up evaluations of the foals for a 3-month
      period did not detect any abnormalities. CONCLUSIONS AND CLINICAL RELEVANCE:
      Administration of the ivermectin-praziquantel paste appears to be safe in
      pregnant mares and their foals.

PMID- 14596458
TI  - Gelatinase activity in synovial fluid and synovium obtained from healthy and
      osteoarthritic joints of dogs.
AB  - OBJECTIVE: To determine matrix metalloproteinase (MMP) activity in synovial fluid
      (SF) obtained from the joints of dogs with degenerative joint disease (DJD)
      secondary to various underlying conditions. SAMPLE POPULATION: 35 samples of SF
      obtained from 18 clinically normal (control) dogs and 34 samples of SF obtained
      from 17 dogs with DJD; dogs with DJD were from 2 populations (client-owned dogs
      and research dogs that had DJD secondary to the lysosomal storage disease
      mucopolysaccharidosis VII). PROCEDURE: MMP activity in samples of SF was
      semiquantitatively examined by use of gelatin or casein zymography. Western blot
      analysis was performed by use of antibodies for MMP-2 and MMP-9. In addition, in
      situ MMP activity was observed in sections of synovial membrane obtained from
      healthy and osteoarthritic joints. RESULTS: Samples of SF from osteoarthritic
      joints had higher MMP-2 activity and dramatically increased MMP-9 activity,
      compared with values for healthy joints. Substrate-overlay analyses indicated
      minimal gelatin-degrading activity in synoviocytes obtained from control dogs,
      whereas greater activity was seen in osteoarthritic synoviocytes, with additional
      activity in the underlying tissue. CONCLUSIONS AND CLINICAL RELEVANCE: Higher MMP
      2 activity and dramatic increases in MMP-9 activity were associated with the
      osteoarthritic state, even though MMP-2 activity was detected in healthy joints.
      This study expands information on MMP production in SF of osteoarthritic joints
      in other species and documents the similarity of MMP activity patterns regardless
      of the cause of DJD.

PMID- 14596459
TI  - Depletion of gentamicin and its major components from various tissues of turkeys.
AB  - OBJECTIVE: To determine tissue depletion profiles for gentamicin and its 3 major
      components (C1, C1a, and C2) in turkeys. ANIMALS: Twenty 10-week-old male
      turkeys. PROCEDURE: birds were maintained as untreated controls. The remaining
      birds were treated with gentamicin sulfate at a dosage of 2 mg/kg, IM, once daily
      for 5 days. Treated birds were euthanatized 45, 60, 75, and 90 days (4 birds at
      each sample time) after the last dose of gentamicin was administered, and samples
      of muscle, liver, kidney, and skin and fat were collected. Control birds were
      euthanatized on day 45. Concentrations of the 3 major components of gentamicin
      were measured by means of reversed-phase high-performance liquid chromatography.
      RESULTS: Total gentamicin concentration (ie, sum of the concentrations of the 3
      major components) was < 100 microg/kg for all muscle and skin and fat samples by
      day 45 and all liver samples by day 75. At all sample times, concentration of the
      gentamicin C1 component was higher than concentrations of the C1a and C2
      components in all tissues. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest
      that tissue depletion profiles of the 3 major components of gentamicin differ
      from each other. Withdrawal time, therefore, may depend on the ratio of the
      components in the pharmaceutical preparation used.

PMID- 14596460
TI  - Development and validation of a radioimmunoassay for the measurement of canine
      pancreatic lipase immunoreactivity in serum of dogs.
AB  - OBJECTIVE: To develop and validate a radioimmunoassay (RIA) for measuring canine
      pancreatic lipase immunoreactivity (cPLI) in serum obtained from dogs. SAMPLE
      POPULATION: Serum samples from 47 healthy dogs. PROCEDURES: Canine pancreatic
      lipase (cPL) was purified from pancreatic specimens of dogs. Antibodies against
      cPL were raised in rabbits and purified by use of affinity chromatography. A
      tracer was produced by iodination of cPL with 125I. An RIA was established and
      validated by determination of sensitivity, working range, dilutional parallelism,
      spiking recovery, and intra- and interassay variability. A reference range for
      cPLI in serum was established by use of the central 95th percentile for samples
      obtained from 47 healthy dogs. RESULTS: Sensitivity and upper limit of the
      working range were 0.88 and 863 microg/L, respectively. Observed-to-expected
      ratios for serial dilutions ranged from 84.9 to 116.5% for 4 samples. Observed-to
      expected ratios for spiking recovery ranged from 82.8 to 128.6% for 4 samples.
      Coefficients of variation for intra-assay variability for 4 serum samples were
      18.3, 4.2, 3.5, and 8.9%, whereas interassay coefficients of variation were 29.2,
      6.2, 3.9, and 4.4%, respectively. The reference range was 4.4 to 276.1 microg/L.
      CONCLUSIONS AND CLINICAL RELEVANCE: We conclude that the RIA described is
      sensitive, linear, accurate, precise, and reproducible, with limited accuracy in
      the high end of the working range and limited precision and reproducibility in
      the low end of the working range. Additional studies are needed to evaluate
      whether this degree of accuracy, precision, and reproducibility will negatively
      impact clinical use of this assay.

PMID- 14596461
TI  - Relationship between orally administered dose, surface emission rate for gamma
      radiation, and urine radioactivity in radioiodine-treated hyperthyroid cats.
AB  - OBJECTIVE: To determine the relationship between surface emission rate of gamma
      radiation and urine concentration of I131 (urine radioactivity) during the period
      7 to 21 days after oral or SC administration of I131 to hyperthyroid cats.
      ANIMALS: 47 hyperthyroid cats administered I131 PO and 24 hyperthyroid cats
      administered I131 SC. PROCEDURE: A dose of I131 (1.78 to 2.04 X 10(2) MBq [4.8 to
      5.5 mCi]) was administered orally. Surface emission at the skin adjacent to the
      thyroid gland on days 7, 10, 14, 18, and 21 and number of counts/30 s in a urine
      sample (1 mL, obtained via cystocentesis) on days 7, 14, and 21 after oral
      administration were measured. Effective half-life (T1/2E) was derived for each
      point. Surface emission thresholds for maximum urine radioactivity values were
      established. A dose of I131 (1.48 X 10(2) MBq [4.0 mCi]) was administered SC.
      Urine radioactivity and surface emission rates for SC administration were
      compared with values for oral administration. RESULTS: The T1/2E for surface
      emissions and urine radioactivity progressively increased toward values for
      physical T1/2 over time. The T1/2E for surface emissions was 2.19 to 4.70 days,
      and T1/2E for urine radioactivity was 2.16 to 3.67 days. Surface emission rates
      had a clinically useful threshold relationship to maximum urine concentrations of
      I131. CONCLUSIONS AND CLINICAL RELEVANCE: Surface emission rates for cats
      administered I131 appeared useful in determining upper limits (threshold) of
      urine radioactivity and are a valid method to assess the time at which cats can
      be discharged after I131 administration.

PMID- 14596462
TI  - Evaluation of erythropoiesis and changes in serum erythropoietin concentration in
      cats after renal transplantation.
AB  - OBJECTIVE: To investigate the clinicopathologic patterns of the erythropoietic
      response after renal transplantation in cats with chronic renal failure (CRF).
      ANIMALS: 14 cats with CRF undergoing renal transplantation. PROCEDURE: Before and
      at intervals during a 6-month period after transplantation, serum creatinine and
      erythropoietin concentrations, Hct, erythrocyte indices, aggregate reticulocyte
      percentage, and iron variables were measured. Additionally, the number of
      transfusions administered to and any complications that developed in each cat
      were recorded. RESULTS: In all cats, preoperative azotemia resolved within 6 days
      after renal transplantation. Two cats had a temporary increase in serum
      creatinine concentration secondary to an acute graft rejection episode. Anemia
      (defined as Hct < 28%) resolved in 10 cats 3 to 49 days after surgery. Resolution
      of anemia was delayed in 2 cats that had acute rejection episodes. Serum
      erythropoietin concentration and reticulocyte percentage were low preoperatively;
      values after surgery were highly variable. Compared with preoperative values,
      serum erythropoietin concentration increased 1 to 4 days after surgery in 11
      cats; between days 5 and 58, another increase was detected in 9 cats. Serum iron
      concentrations were generally low before and 14 days after transplantation.
      CONCLUSION AND CLINICAL RELEVANCE: The erythropoietic response was highly
      variable in cats after renal transplantation, but anemia typically resolved
      within 1 month after surgery. A delay in resolution of anemia in cats may
      indicate poor graft function and inadequate iron stores, suggesting the need for
      further evaluation for concurrent illness.

PMID- 14596463
TI  - In vitro evaluation of the distribution of blood flow within a canine bipedicled
      latissimus dorsi muscle flap.
AB  - OBJECTIVE: To identify the predominant perforating artery in the canine
      latissimus dorsi muscle and demonstrate that perfusion of the predominant
      perforating artery improves blood flow in segments of the latissimus dorsi muscle
      that are located distally from the thoracodorsal artery. SAMPLE POPULATION:
      Latissimus dorsi muscles dissected from 7 dogs. PROCEDURES: Colored microspheres
      were used to determine the degree of perfusion of the latissimus dorsi muscle via
      the thoracodorsal artery, predominant perforating artery, or the thoracodorsal
      artery and predominant perforating artery together. The latissimus dorsi muscle
      was divided into 4 proximal to distal segments relative to the thoracodorsal
      artery (segments A, B, C, and D, respectively). RESULTS: The perforating artery,
      located at the level of the fifth intercostal space, predominantly supplied
      perfusion to segments B, C, and D. The number of microspheres received by segment
      C was significantly higher when the thoracodorsal artery and perforating artery
      were used for muscle perfusion (181.40 +/- 44.90 microspheres/300 g of tissue for
      every 3,000 spheres injected), compared with use of the thoracodorsal artery
      alone (60.00 +/- 13.70 microspheres/300 g of tissue for every 3,000 spheres
      injected). CONCLUSIONS AND CLINICAL RELEVANCE: Blood flow via the predominant
      perforating artery improves perfusion to the middle part of the latissimus dorsi
      muscle in dogs. A bipedicled latissimus dorsi muscle flap would provide a
      healthier muscle for cardiac assist in the treatment of dilated cardiomyopathy in
      dogs.

PMID- 14596464
TI  - Determination of reference range values indicative of glucose metabolism and
      insulin resistance by use of glucose clamp techniques in horses and ponies.
AB  - OBJECTIVES: To acquire reference range values indicative of glucose metabolism by
      use of the hyperglycemic clamp technique in healthy horses and evaluate the
      usefulness of the euglycemic hyperinsulinemic clamp technique in healthy horses
      and ponies. ANIMALS: Dutch Warmblood horses and 4 Shetland ponies. PROCEDURE: The
      hyperglycemic clamp technique was used for quantification of the sensitivity of
      beta cells to exogenous glucose infusion in horses. The euglycemic
      hyperinsulinemic clamp technique was used to determine the sensitivity and
      responsiveness of tissues to exogenous insulin in horses and ponies. RESULTS:
      During the hyperglycemic clamp technique, the mean amount of glucose metabolized
      (M) in horses was 0.011 +/- 0.0045 mmol/kg x min(-1) (95% confidence interval
      [CI], 0.0018 to 0.020 mmol/kg x min(-1); range, 0.000035 to 0.021 mmol/kg x min(
      1)) and the mean M value-to-plasma insulin concentration (I) ratio (ie, mmol of
      glucose/kg x min(-1) per pmol of insulin/L x 100) was 0.017 +/- 0.016 (95% CI, 
      0.014 to 0.049; range, 0.000025 to 0.055). During the euglycemic hyperinsulinemic
      clamp technique, the mean M value was 0.014 +/- 0.0055 mmol/kg x min(-1) (95% CI,
      0.0026 to 0.025 mmol/kg x min(-1); range, 0.0042 to 0.023 mmol/kg x min(-1)) in
      horses and 0.0073 +/- 0.0020 mmol/kg x min(-1) (95% CI, 0.0034 to 0.011 mmol/kg x
      min(-1); range, 0.0049 to 0.011 mmol/kg x min(-1)) in ponies. The M value was
      significantly lower in ponies than in horses, whereas the M:I ratios were not
      significantly different between horses and ponies. CONCLUSION AND CLINICAL
      RELEVANCE: Glucose clamp techniques offer good methods to investigate glucose
      metabolism in horses and ponies. A higher degree of insulin resistance was found
      in ponies, compared with Dutch Warmblood horses.

PMID- 14596465
TI  - Effects of carnitine and taurine on fatty acid metabolism and lipid accumulation
      in the liver of cats during weight gain and weight loss.
AB  - OBJECTIVE: To determine the effects of carnitine (Ca) or taurine (Ta)
      supplementation on prevention of lipid accumulation in the liver of cats.
      ANIMALS: 24 adult cats. PROCEDURE: Cats were fed a weight-gaining diet sufficient
      in n-6 polyunsaturated fatty acids (PUFAs), low in long-chain n-3 PUFAs (n-3
      LPUFA), and containing corn gluten for 20 weeks. Cats gained at least 30% in body
      weight and were assigned to 4 weight-reduction diets (6 cats/diet) for 7 to 10
      weeks (control diet, control plus Ca, control plus Ta, and control plus Ca and
      Ta). RESULTS: Hepatic lipids accumulated significantly during weight gain and
      weight loss but were not altered by Ca orTa after weight loss. Carnitine
      significantly increased n-3 and n-6 LPUFAs in hepatic triglycerides, decreased
      incorporation of 13C palmitate into very-low-density lipoprotein and hepatic
      triglycerides, and increased plasma ketone bodies. Carnitine also significantly
      increased weight loss but without altering the fat to lean body mass ratio.
      Taurine did not significantly affect any variables. Diets low in n-3 LPUFAs
      predisposed cats to hepatic lipidosis during weight gain, which was further
      exacerbated during weight loss. Mitochondrial numbers decreased during weight
      gain and weight loss but were not affected by treatment. Carnitine improved fatty
      acid oxidation and glucose utilization during weight loss without correcting
      hepatic lipidosis. CONCLUSIONS AND CLINICAL RELEVANCE: The primary mechanism
      leading to hepatic lipidosis in cats appears to be decreased fatty acid
      oxidation. Carnitine may improve fatty acid oxidation but will not ameliorate
      hepatic lipidosis in cats fed a diet low in n-3 fatty acids.

PMID- 14596466
TI  - Pharmacokinetics of ceftiofur sodium after intramuscular or subcutaneous
      administration in green iguanas (Iguana iguana).
AB  - OBJECTIVE: To determine the pharmacokinetics of ceftiofur sodium after IM and SC
      administration in green iguanas. ANIMALS: 6 male and 4 female adult green
      iguanas. PROCEDURE: In a crossover design, 5 iguanas received a single dose of
      ceftiofur sodium (5 mg/kg) IM, and 5 iguanas received the same dose SC. Blood
      samples were taken at 0, 20, and 40 minutes and 1, 2, 4, 8, 24, 48, and 72 hours
      after administration. After a 10-week washout period, each iguana was given the
      same dose via the reciprocal administration route, and blood was collected in the
      same fashion. Ceftiofur free-acid equivalents were measured via high-performance
      liquid chromatography. RESULTS: The first phase intercepts were significantly
      different between the 2 administration routes. Mean maximum plasma concentration
      was significantly higher with the IM (28.6 +/- 8.0 microg/mL) than the SC (18.6
      +/- 8.3 microg/mL) administration route. There were no significant differences
      between terminal half-lives (harmonic mean via IM route, 15.7 +/- 4.7 hours;
      harmonic mean via SC route, 19.7 +/- 6.7 hours) and mean areas under the curve
      measured to the last time point (IM route, 11,722 +/- 7,907 microg x h/mL; SC
      route, 12,143 +/- 9,633 microg x h/mL). Ceftiofur free-acid equivalent
      concentrations were maintained > or = 2 microg/mL for > 24 hours via both routes.
      CONCLUSIONS AND CLINICAL RELEVANCE: A suggested dosing schedule for ceftiofur
      sodium in green iguanas for microbes susceptible at > 2 microg/mL would be 5
      mg/kg, IM or SC, every 24 hours.

PMID- 14596467
TI  - Effect of first-pass hepatic metabolism on the disposition of levamisole after
      intravenous administration in rabbits.
AB  - OBJECTIVE: To evaluate the contribution of first-pass hepatic metabolism of
      levamisole on levamisole disposition in rabbits. ANIMALS: 30 male New Zealand
      White rabbits. PROCEDURES: Rabbits were randomly placed into 2 groups. Rabbits in
      the first group received levamisole via the marginal ear vein at the following 3
      doses: 12.5, 16, and 20 mg/kg (5 rabbits for each dose). Rabbits of the second
      group received levamisole via the jejunal vein at the same doses (5 rabbits
      each). During the following 240-minute period, plasma samples were obtained and
      quantified for levamisole concentrations by reversed-phase high-performance
      liquid chromatography. RESULTS: No significant differences were found between
      pharmacokinetic parameters calculated by compartmental or noncompartmental
      analysis. Mean hepatic extraction ratio ranged from -0.044 to 0.017 and from
      0.020 to 0.081 when area under the plasma concentration-time curve values were
      obtained after compartmental or noncompartmental analysis, respectively. After
      compartmental analysis, plasma concentration decreased bi-exponentially. Mean
      pharmacokinetic parameter values were as follows for each dose (12.5, 16, and 20
      mg/kg, respectively): after levamisole administration via the marginal ear vein,
      volume of distribution at steady state (Vss) = 4.26, 4.33, and 3.20 L/kg; total
      body clearance (CI) = 49.04, 43.77, and 39.26 mL/kg x min; and half-life
      associated with beta-phase (t1/2beta) = 77.93, 85.39, and 69.79 minutes. After
      levamisole administration via the jejunal vein, Vss = 4.38, 2.85, and 2.97 L/kg;
      CI = 48.14, 42.40, and 39.69 mL/kg x min; and t1/2b = 101.9, 76.71, and 76.13
      minutes. CONCLUSIONS: Levamisole has a low degree of hepatic extraction in
      rabbits.

PMID- 14596468
TI  - Comparison of the effect of propofol and sevoflurane on the urethral pressure
      profile in healthy female dogs.
AB  - OBJECTIVE: To compare the effects of propofol and sevoflurane on the urethral
      pressure profile in female dogs. ANIMALS: 10 healthy female dogs. PROCEDURE:
      Urethral pressure profilometry was performed in awake dogs, during anesthesia
      with sevoflurane at 1.5, 2.0, and 3.0% end-tidal concentration, and during
      infusion of propofol at rates of 0.4, 0.8, and 1.2 mg/kg/min. A consistent plane
      of anesthesia was maintained for each anesthetic protocol. Maximum urethral
      pressure, maximum urethral closure pressure, functional profile length, and
      functional area were measured. RESULTS: Mean maximum urethral closure pressure of
      awake dogs was not significantly different than that of dogs anesthetized with
      propofol at all infusion rates or with sevoflurane at 1.5 and 2.0% end-tidal
      concentration. Functional area in awake dogs was significantly higher than in
      anesthetized dogs. Functional area of dogs during anesthesia with sevoflurane at
      3.0% end-tidal concentration was significantly lower than functional area for
      other anesthetic protocols. Individual differences in the magnitude of effects of
      propofol and sevoflurane on urethral pressures were observed. CONCLUSIONS AND
      CLINICAL RELEVANCE: Sevoflurane is an alternative to propofol for anesthesia in
      female dogs undergoing urethral pressure profilometry. Use of these anesthetics
      at appropriate administration rates should reliably distinguish normal from
      abnormal maximum urethral closure pressures and functional areas. Titration of
      anesthetic depth is a critical component of urodynamic testing.

PMID- 14596469
TI  - Evaluation of T lymphocytes in captive african lions (Panthera leo) infected with
      feline immunodeficiency virus.
AB  - OBJECTIVE: To determine whether FIV infection in captive African lions is
      associated with changes in immune cell variables similar to those detected in
      domestic cats infected with FIV. ANIMALS: 5 captive African lions naturally
      infected with FIV (FIV+) and 5 lions not infected with FIV (FIV-). PROCEDURE:
      Peripheral blood samples were collected from FIV+ lions during annual
      examinations conducted during a 7-year period and at a single time point from the
      FIV- lions. From results of CBC and flow cytometry, lymphocyte subsets were
      characterized and compared. RESULTS: Flow cytometric analysis revealed that the
      percentage and absolute number of CD4+ and CD8+ T cells were significantly lower
      in FIV+ lions, compared with these values in FIV- lions. In FIV+ lions, severe
      depletion in the absolute number of CD4+ and CD8+ T cells was detected, although
      this did not correlate with clinical signs. Muscle wasting was the most
      consistent clinical sign of infection. CONCLUSIONS AND CLINICAL RELEVANCE:
      Results suggest that FIV+ African lions develop lymphocyte deficiencies,
      including significant decreases in the absolute number of CD4+ and CD8+ T cells;
      these findings of immune dysfunction are similar to those defined for FIV+
      domestic cats. It is important to monitor the number of CD4+ T cells in infected
      animals as a measure of disease progression.

PMID- 14596470
TI  - Quantitation of house dust mites and house dust mite allergens in the
      microenvironment of dogs.
AB  - OBJECTIVE: To quantitate the density of Dermatophagoides farinae and D
      pteronyssinus and concentrations of house dust mite (HDM) allergens (Der f 1, Der
      p 1, and Group 2 allergens) in the indoor microenvironment of dogs. Sample
      Population-50 homes in Columbus, Ohio. PROCEDURES: n each home, samples of dust
      were collected from 3 locations in which dogs spent most time. Whenever possible,
      the species of mites collected was identified. Mite density (mites/g of dust) was
      assessed, and allergen concentrations were assayed by standardized ELISAs.
      Relative humidity and temperature in each home were monitored during a 5-day
      period. Characteristics of homes and sample sources were evaluated. RESULTS: Dust
      samples from all 50 homes contained > or = 1 HDM allergen; Der f 1 and Der p 1
      were detected in 100 and 74% of homes, respectively. Fifteen homes had HDMs;
      compared with D pteronyssinus, D farinae was found more commonly (14/15 homes)
      and at a higher density. Basements, homes without central air-conditioning, and
      dog beds that were > or = 1 year old had high HDM allergen concentrations. Homes
      with > or = 2 microg of Der f 1 or Group 2 allergens/g of dust or > or = 100
      mites/g of dust were significantly more likely to have a maximum relative
      humidity > or = 75%. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate the
      presence of HDMs and HDM allergens in the specific microenvironment of dogs in
      homes. Factors associated with high levels of exposure were identified, which may
      be associated with increased risk for sensitization and development of atopic
      diseases.

PMID- 14596471
TI  - Evaluation of progesterone and estrogen receptor expression in 15 meningiomas of
      dogs and cats.
AB  - OBJECTIVE: To evaluate progesterone and estrogen receptor expression in
      meningiomas of the CNS in dogs and cats. ANIMAL: 8 dogs (1 of which was treated
      with gestrinone) and 5 cats with intracranial meningiomas and 2 dogs with spinal
      cord meningiomas; tissue samples were also obtained from 1 clinically normal dog
      and 1 clinically normal cat. PROCEDURE: Meningioma tissue was obtained during
      surgery or at necropsy; samples were processed for histologic classification and
      immunohistochemical evaluation of the proportion of tumor cells with progesterone
      and estrogen receptors. Correlation among receptor expression, tumor grade, and
      histologic subtypes was determined. RESULT: Several histologic subtypes of
      intracranial meningiomas were detected among tissue samples. In the cats, all
      intracranial meningiomas were benign. Progesterone receptor immunoreactivity was
      detected in 14 of 15 meningiomas. Progesterone receptor expression was identified
      in > 80% of cells in 8 intracranial meningiomas (4 dogs and 4 cats) and 2 spinal
      cord meningiomas. In samples of malignant transitional and granular cell
      meningiomas in dogs, progesterone receptors were detected in 32 and 4.8% of cells
      respectively. In 1 cat, 38% of tumor cells had progesterone receptors. In a dog
      treated with gestrinone, no progesterone receptors were detected in the
      intracranial meningioma. Estrogen receptors were only detected in the tumor of 1
      dog. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate a high proportion of
      progesterone receptors in cells of meningiomas of the CNS in dogs and cats.
      Antiprogesterone treatment may have a role in the treatment of unresectable or
      recurrent meningiomas in dogs and cats.

PMID- 14596472
TI  - Epidemiologic characteristics and management of polysaccharide storage myopathy
      in Quarter Horses.
AB  - OBJECTIVE: To characterize onset and clinical signs of polysaccharide storage
      myopathy (PSSM) in a well-defined population of affected Quarter Horses, identify
      risk factors for PSSM, determine compliance of owners to dietary and exercise
      recommendations, and evaluate the efficacy of dietary and exercise
      recommendations. ANIMALS: 40 Quarter Horses with PSSM and 37 unaffected control
      horses. PROCEDURES: Owners of horses with PSSM completed a retrospective
      questionnaire concerning their horse's condition. RESULTS: Between horses with
      PSSM and control horses, no significant differences were found in sex
      distribution (21 vs 15 females and 16 vs 22 males, respectively), temperament,
      muscle build, diet, or amount of turnout. In horses with PSSM, signs of muscle
      stiffness, muscle fasciculations, sweating, exercise intolerance, weakness,
      muscle wasting, reluctance to move, colic, abnormal gait, recumbency, lameness,
      and swollen muscles began between the age of 1 day and 14 years (mean age, 4.9 +/
      3.5 years). Five horses with PSSM developed acute muscle atrophy. Sixty-three
      percent (25/40) of owners fed the recommended diet, 55% (22/40) provided regular
      exercise, and 40% (16/40) followed both dietary and exercise recommendations.
      Owners of affected horses for which a decrease in severity or frequency of PSSM
      was not found did not follow the exercise, dietary, or both recommendations. All
      horses for which both dietary and exercise recommendations were followed had
      improvement in signs of PSSM. CONCLUSIONS AND CLINICAL RELEVANCE: n addition to
      exertional rhabdomyolysis, signs of PSSM include acute muscle atrophy and gait
      abnormalities. It appears that PSSM can be managed by following dietary
      recommendations combined with gradual increases in daily exercise.

PMID- 14596473
TI  - A further look at the "language-as-fixed-effect fallacy".
AB  - The proper analysis of experiments using language materials has been a source of
      controversy and debate among researchers. We summarize the main issues and
      discuss the solutions that have been presented. Even though the major issues have
      been dealt with extensively in the literature, there still exists quite a bit of
      confusion about how to analyze the data from such experiments. We discuss a
      number of the most frequently voiced objections. In particular, we discuss the
      issue of what happens if in a counterbalanced design only some of the items show
      the treatment effect. Finally, a possible solution is discussed for the case
      where only partial matching of items between conditions is possible.

PMID- 14596474
TI  - Using the analysis of covariance to increase the power of priming experiments.
AB  - Although priming paradigms are widely used in cognitive psychology, the
      statistical analyses typically applied to priming data may not be optimal.
      Conceiving of priming paradigms as change-from-baseline designs suggests that the
      analysis of covariance (ANCOVA), using baseline performance as the covariate, is
      a more efficient (i.e., powerful) analysis. Specifically, ANCOVA provides more
      powerful tests of 1) the presence of priming and 2) between-group differences in
      priming. In addition, for within-subject designs with multiple baseline
      conditions, ANCOVA may increase the power of within-subjects effects. Efficiency
      gains are demonstrated with a re-analysis of priming datasets from implicit
      memory research. It is suggested that similar gains may be realized in other
      areas of priming research. Important assumptions of this procedure, which must be
      evaluated for the appropriate application of ANCOVA, are discussed.

PMID- 14596475
TI  - Basic statistics and the inconsistency of multiple comparison procedures.
AB  - This paper has two main themes. First, the various statistical measures used in
      this journal are summarized and their interrelationships described by way of a
      flow chart. These are the pooled standard deviation, the pooled variance or mean
      square error (MSE), the standard error of each treatment mean (SEM) and of the
      difference between two treatment means (SED), and the least difference between
      two means which is significant at (e.g.) the 5% level of significance (LSD(5%)).
      The last three measures can be displayed as vertical bars in graphs, and the
      relationship between the lengths of these bars is graphically illustrated. It is
      suggested that the LSD is the most useful of these three measures. Second, when
      the experimenter has no prior hypotheses to be tested using analysis of variance
      "contrasts," a multiple comparison procedure (MCP) that examines all pair-wise
      differences between treatment means, may be appropriate. In this paper a
      fictitious experimental data set is used to compare several well-known McPs by
      focussing on a particular operating characteristic, the consistency of the
      results between an overall analysis of all treatments and an analysis of a subset
      of the experimental treatments. The procedure that behaves best according to this
      criterion is the unrestricted least significant difference (LSD) procedure. The
      unrestricted LSD is therefore recommended with the proviso that it be used as a
      method of generating hypotheses to be tested in subsequent experimentation, not
      as a method that attempts to simultaneously formulate and test hypotheses.

PMID- 14596476
TI  - Statistical testing and null distributions: what to do when samples are not
      random.
AB  - Selected literature related to statistical testing is reviewed to compare the
      theoretical models underlying parametric and nonparametric inference.
      Specifically, we show that these models evaluate different hypotheses, are based
      on different concepts of probability and resultant null distributions, and
      support different substantive conclusions. We suggest that cognitive scientists
      should be aware of both models, thus providing them with a better appreciation of
      the implications and consequences of their choices among potential methods of
      analysis. This is especially true when it is recognized that most cognitive
      science research employs design features that do not justify parametric
      procedures, but that do support nonparametric methods of analysis, particularly
      those based on the method of permutation/randomization.

PMID- 14596477
TI  - The p-value fallacy and how to avoid it.
AB  - Null hypothesis significance tests are commonly used to provide a link between
      empirical evidence and theoretical interpretation. However, this strategy is
      prone to the "p-value fallacy" in which effects and interactions are classified
      as either "noise" or "real" based on whether the associated p value is greater or
      less than .05. This dichotomous classification can lead to dramatic misconstruals
      of the evidence provided by an experiment. For example, it is quite possible to
      have similar patterns of means that lead to entirely different patterns of
      significance, and one can easily find the same patterns of significance that are
      associated with completely different patterns of means. Describing data in terms
      of an inventory of significant and nonsignificant effects can thus completely
      misrepresent the results. An alternative analytical technique is to identify
      competing interpretations of the data and then use likelihood ratios to assess
      which interpretation provides the better account. Several different methods of
      calculating the likelihood ratios are illustrated. It is argued that this
      approach satisfies a principle of "graded evidence," according to which similar
      data should provide similar evidence.

PMID- 14596478
TI  - Using confidence intervals for graphically based data interpretation.
AB  - As a potential alternative to standard null hypothesis significance testing, we
      describe methods for graphical presentation of data--particularly condition means
      and their corresponding confidence intervals--for a wide range of factorial
      designs used in experimental psychology. We describe and illustrate confidence
      intervals specifically appropriate for between-subject versus within-subject
      factors. For designs involving more than two levels of a factor, we describe the
      use of contrasts for graphical illustration of theoretically meaningful
      components of main effects and interactions. These graphical techniques lend
      themselves to a natural and straightforward assessment of statistical power.

PMID- 14596479
TI  - Effect sizes for experimenting psychologists.
AB  - This article describes three families of effect size estimators and their use in
      situations of general and specific interest to experimenting psychologists. The
      situations discussed include both between- and within-group (repeated measures)
      designs. Also described is the counternull statistic, which is useful in
      preventing common errors of interpretation in null hypothesis significance
      testing. The emphasis is on correlation (r-type) effect size indicators, but a
      wide variety of difference-type and ratio-type effect size estimators are also
      described.

PMID- 14596480
TI  - Is the area measure a historical anomaly?
AB  - Green's well-known area theorem establishes an equivalence between the area under
      the yes-no ROC curve and the percent correct of an unbiased observer in a two
      alternative forced-choice (2AFC) task with equivalent stimuli. In this article,
      we show that this conversion from yes-no detection data to hypothetical
      performance in a 2AFC task is unnecessary: The same yes-no detection data that
      are used to compute the area statistic can always be used to compute the percent
      correct of an unbiased observer in the yes-no detection task itself. We also show
      that the ROC curve may not be the ideal graphical device for many investigators.
      A more natural representation of the difficulty of a discrimination task is
      obtained by plotting the distribution of the posterior betting odds under equal
      base rates, which can be estimated from their distributions under unequal base
      rates. Finally, unlike the area measure and other traditional detection theory
      statistics, both the yes-no percent correct measure and the odds distributions
      generalize in an obvious and direct way to classification paradigms with more
      than two responses (e.g., identification).

PMID- 14596481
TI  - Multiway frequency analysis for experimental psychologists.
AB  - Many research designs in experimental psychology generate data that are
      fundamentally discrete or categorical in nature, and produce multiway tables of
      frequencies. Despite an extensive and, more recently, accessible literature on
      the topic, multiway frequency analysis is rarely used in experimental psychology.
      A reason may be the form of exposition in the literature, with emphases and
      concerns far removed from those of the typical experimental psychologist. An
      approach to multiway frequency analysis for experimental psychologists is
      described that has the features we want: asymmetrical designs, factors assessed
      for their respective main and interactive effects in a manner analogous to ANOVA,
      and the ability to handle within-subject designs.

PMID- 14596483
TI  - Institute of Aging.

PMID- 14596482
TI  - 2003 Canadian Society for Clinical Investigation award winners: profiles.

PMID- 14596484
TI  - X-linked inhibitor regulating TRAIL-induced apoptosis in chemoresistant human
      primary glioblastoma cells.
AB  - INTRODUCTION: The X-chromosome-linked inhibitor of apoptosis protein (XIAP)
      prevents apoptosis from activated transmembrane death receptors and confers
      tumour resistance to irradiation and chemotherapy. Despite the important
      oncologic implications, data concerning glioblastoma in this regard are few and
      isolated. The objective of this study was to examine the role of XIAP in the
      signalling pathway of TRAIL (tumour necrosis factor-related apoptosis-inducing
      ligand)-mediated apoptosis in chemoresistant human glioblastoma cells. METHOD:
      Downregulators of XIAP, low-dose cisplatin, etoposide (VP 16) or second
      mitochondria-derived activator of caspase (Smac)-Tat peptide, were applied to 2
      chemoresistant glioblastoma cell lines of fresh isolates to identify the impact
      of these sensitizing agents on the cytotoxicity of TRAIL. Hoechst staining for
      apoptotic nuclear morphology and Western blot analysis for the corresponding
      levels of proteins that regulate apoptotic pathways including XIAP were
      performed. The involvement of mitochondrial pathways marked by the release of
      cytochrome c or Smac/direct IAP (inhibitor of apoptosis protein)-binding protein
      with low P1 (DIABLO), or both, was assessed by confocal fluorescence microscopy.
      RESULTS: Downregulators of XIAP induced apoptosis in a dose-dependent manner with
      TRAIL in 1 chemoresistant glioblastoma cell line. Here, XIAP downregulation
      modulated by Smac-Tat peptide resulted in increased TRAIL-induced cell death. In
      addition, TRAIL was shown to enhance the translocation of Smac/DIABLO from
      mitochondria to the cytosol in cells that underwent apoptosis, which in turn
      neutralized XIAP activity. In comparison, the second chemoresistant glioblastoma
      cell line showed no regulatory XIAP effect. This finding correlates with the
      upstream effect of mutant p53 and BCL-X(L) status that were upregulated in this
      chemoresistant cell line. CONCLUSION: These results support the use of selective
      or tailored therapeutic strategies that synergistically sensitize chemoresistant
      glioblastoma to TRAIL-mediated apoptosis by administering appropriate XIAP
      downregulating agents.

PMID- 14596486
TI  - The shape of things to come: chondrocytes and osteoarthritis.

PMID- 14596485
TI  - Chronic pulmonary disease in rural women exposed to biomass fumes.
AB  - INTRODUCTION: Biomass (organic) fuels cause indoor air pollution when used inside
      dwellings. We evaluated the frequencies of chronic obstructive pulmonary disease
      (COPD) and chronic bronchitis (CB) among rural women using biomass fuels for
      heating and cooking and compared them to women living in urban areas where such
      fuels are not used. METHODS: From electoral lists we randomly selected 242 women
      living in rural areas near Kayseri, Turkey and 102 women living in apartments in
      the city having central heating and cooking with fuels other than biomass ones.
      Using a translated version of the American Thoracic Society questionnaire, with
      additional questions from the British Medical Research Council questionnaire,
      trained interviewers conducted personal interviews. They also collected
      information on fuels used for cooking and heating. All study subjects underwent a
      physical examination and measurement of pulmonary function. RESULTS: We found
      that rural women were younger than urban women (mean age [and standard
      deviation], 40.5 [14.1] yr v. 43.6 [11.9] yr). More urban than rural women were
      current (14.7% v. 4.5%, p < 0.001) or past (11.8% v. 1.2%, p < 0.001) smokers. CB
      was more prevalent among rural women than urban women (20.7% v. 10.8%, p < 0.03).
      Similarly, COPD was more prevalent in rural women (12.4% v. 3.9%, p < 0.05).
      Although the pulmonary function tests were within normal limits, FEV, values in
      rural women were found to be relatively low compared with those of urban women (p
      < 0.05). INTERPRETATION: Rural women exposed to biomass fumes are more likely to
      suffer from CB and COPD than urban women even though the prevalence of smoking is
      higher among the latter group.

PMID- 14596487
TI  - Molecular genetics of autosomal dominant polycystic kidney disease.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is a common Mendelian
      disorder, occurring in approximately 1 in 1000 births and accounting for 8% to
      10% of cases of end-stage renal disease (ESRD). Mutations of 2 genes, PKD1 and
      PKD2, account for the disease in approximately 80% to 85% and 10% to 15% of
      families respectively. The gene products (polycystin 1 and 2) of PKD1 and PKD2
      are plasma membrane proteins and components of a novel signalling pathway that
      regulates epithelial cell growth and differentiation. Significant inter- and
      intrafamilial renal disease variability in ADPKD has been well documented and is
      influenced by both germline and somatic genetic events. Specifically, genetic
      locus heterogeneity and 2 rare Mendelian syndromes have been shown to strongly
      influence the variability of interfamilial renal disease, and as-yet-unknown
      genetic and environmental factors likely modify both inter- and intrafamilial
      renal disease severity. Furthermore, individual cyst formation in ADPKD
      represents an aberration of monoclonal growth triggered by somatic PKD1 or PKD2
      mutations within individual epithelial cells. Current studies are in progress to
      identify major genetic and environmental modifiers of renal disease variability.
      A thorough knowledge of these determinants will allow better patient risk
      assessment and development of mechanism-based therapy in ADPKD.

PMID- 14596488
TI  - Computer telephony: automated calls for medical care.
AB  - BACKGROUND: The computer telephony system (CTS) combines computer and telephone
      to automate the collection, processing and dissemination of information. Many
      innovative applications of the CTS have emerged. In this article we summarize the
      evidence for CTS-based medical interventions based on randomized controlled
      trials. METHODS: We searched for trials in MEDLINE, CINAHL, the Cochrane Central
      Register of Controlled Trials, and bibliographies of retrieved articles, review
      articles and textbooks. We excluded non-English articles and those pertaining to
      psychology, addiction, psychiatry, research and education. RESULTS: In health
      care delivery, 3 of 4 trials of CTS-based interventions improved clinic show
      rates. In preventive health care, 4 of 5 showed higher childhood immunization
      rates. For nutrition, 2 small trials showed no clear benefit in cholesterol
      lowering or in weight reduction, but 1 trial showed a benefit in fibre intake.
      For increasing physical activity, 1 smaller trial showed no benefit but a larger
      one did. For medical management of chronic conditions, 1 trial showed improved
      hemoglobin A(1c) levels and 1 trial showed better processes of care in diabetes.
      In hypertension management, 1 trial found better adherence to medication regimens
      and control of blood pressure. In outpatient oncology care, 1 trial showed better
      supportive care. For support of caregivers for dementia patients, 1 trial showed
      no benefit. One small trial showed better adherence to medication in seniors.
      CONCLUSIONS: The CTS has diverse applications in medical care; however, the
      evidence for these is limited. Despite being impersonal, the reliability and
      availability of the CTS make it attractive for reminders and follow-up. More
      research is needed to determine the role of the CTS in medical care.

PMID- 14596489
TI  - How meta-analysis increases statistical power.
AB  - One of the most frequently cited reasons for conducting a meta-analysis is the
      increase in statistical power that it affords a reviewer. This article
      demonstrates that fixed-effects meta-analysis increases statistical power by
      reducing the standard error of the weighted average effect size (T.) and, in so
      doing, shrinks the confidence interval around T.. Small confidence intervals make
      it more likely for reviewers to detect nonzero population effects, thereby
      increasing statistical power. Smaller confidence intervals also represent
      increased precision of the estimated population effect size. Computational
      examples are provided for 3 effect-size indices: d (standardized mean
      difference), Pearson's r, and odds ratios. Random-effects meta-analyses also may
      show increased statistical power and a smaller standard error of the weighted
      average effect size. However, the authors demonstrate that increasing the number
      of studies in a random-effects meta-analysis does not always increase statistical
      power.

PMID- 14596490
TI  - Modern robust data analysis methods: measures of central tendency.
AB  - Various statistical methods, developed after 1970, offer the opportunity to
      substantially improve upon the power and accuracy of the conventional t test and
      analysis of variance methods for a wide range of commonly occurring situations.
      The authors briefly review some of the more fundamental problems with
      conventional methods based on means; provide some indication of why recent
      advances, based on robust measures of location (or central tendency), have
      practical value; and describe why modern investigations dealing with nonnormality
      find practical problems when comparing means, in contrast to earlier studies.
      Some suggestions are made about how to proceed when using modern methods.

PMID- 14596491
TI  - Repeated-measures contrasts for "multiple-pattern" hypotheses.
AB  - Contrast analysis of repeated-measures data generally focuses on hypotheses when
      only 1 pattern of results is of theoretical interest. This article articulates a
      framework for contrast analysis in repeated-measures contexts in which
      researchers have hypotheses relevant to 1 potential pattern or multiple potential
      patterns of results. For example, a researcher might ask whether participants
      exhibit a pattern of (a) immediate symptom reduction or (b) delayed symptom
      reduction. Alternatively, the researcher might ask whether 2 or more groups
      exhibit 2 or more patterns to differing degrees. Building on the familiar logic
      and computational procedures for 1-pattern hypotheses, the authors present a
      contrast analysis framework that integrates analysis of 1-pattern and multiple
      pattern hypotheses and accommodates 1 group or multiple groups of participants.

PMID- 14596492
TI  - Local optima in K-means clustering: what you don't know may hurt you.
AB  - The popular K-means clustering method, as implemented in 3 commercial software
      packages (SPSS, SYSTAT, and SAS), generally provides solutions that are only
      locally optimal for a given set of data. Because none of these commercial
      implementations offer a reasonable mechanism to begin the K-means method at
      alternative starting points, separate routines were written within the MATLAB
      (Math-Works, 1999) environment that can be initialized randomly (these routines
      are provided at the end of the online version of this article in the PsycARTICLES
      database). Through the analysis of 2 empirical data sets and 810 simulated data
      sets, it is shown that the results provided by commercial packages are most
      likely locally optimal. These results suggest the need for some strategy to study
      the local optima problem for a specific data set or to identify methods for
      finding "good" starting values that might lead to the best solutions possible.

PMID- 14596493
TI  - Sample size for multiple regression: obtaining regression coefficients that are
      accurate, not simply significant.
AB  - An approach to sample size planning for multiple regression is presented that
      emphasizes accuracy in parameter estimation (AIPE). The AIPE approach yields
      precise estimates of population parameters by providing necessary sample sizes in
      order for the likely widths of confidence intervals to be sufficiently narrow.
      One AIPE method yields a sample size such that the expected width of the
      confidence interval around the standardized population regression coefficient is
      equal to the width specified. An enhanced formulation ensures, with some
      stipulated probability, that the width of the confidence interval will be no
      larger than the width specified. Issues involving standardized regression
      coefficients and random predictors are discussed, as are the philosophical
      differences between AIPE and the power analytic approaches to sample size
      planning.

PMID- 14596494
TI  - Using the expectation maximization algorithm to estimate coefficient alpha for
      scales with item-level missing data.
AB  - A 2-step approach for obtaining internal consistency reliability estimates with
      item-level missing data is outlined. In the 1st step, a covariance matrix and
      mean vector are obtained using the expectation maximization (EM) algorithm. In
      the 2nd step, reliability analyses are carried out in the usual fashion using the
      EM covariance matrix as input. A Monte Carlo simulation examined the impact of 6
      variables (scale length, response categories, item correlations, sample size,
      missing data, and missing data technique) on 3 different outcomes: estimation
      bias, mean errors, and confidence interval coverage. The 2-step approach using EM
      consistently yielded the most accurate reliability estimates and produced
      coverage rates close to the advertised 95% rate. An easy method of implementing
      the procedure is outlined.

PMID- 14596495
TI  - Distributional assumptions of growth mixture models: implications for
      overextraction of latent trajectory classes.
AB  - Growth mixture models are often used to determine if subgroups exist within the
      population that follow qualitatively distinct developmental trajectories.
      However, statistical theory developed for finite normal mixture models suggests
      that latent trajectory classes can be estimated even in the absence of population
      heterogeneity if the distribution of the repeated measures is nonnormal. By
      drawing on this theory, this article demonstrates that multiple trajectory
      classes can be estimated and appear optimal for nonnormal data even when only 1
      group exists in the population. Further, the within-class parameter estimates
      obtained from these models are largely uninterpretable. Significant predictive
      relationships may be obscured or spurious relationships identified. The
      implications of these results for applied research are highlighted, and future
      directions for quantitative developments are suggested.

PMID- 14596496
TI  - Mixture or homogeneous? Comment on Bauer and Curran (2003).
AB  - D. J. Bauer and P. J. Curran (2003) raised some interesting issues with respect
      to mixture models of growth curves. Many useful lessons can be learned from their
      work, and more can be learned by extending the inquiry in related directions.
      These lessons involve the following issues: (a) what a mixture distribution looks
      like, (b) the meaning of the term homogeneous distribution, (c) the importance of
      model checking, (d) advantages and disadvantages of using mixtures and similar
      procedures to approximate complicated distributions, and (e) intrinsic versus
      nonintrinsic transformability.

PMID- 14596497
TI  - Statistical and substantive checking in growth mixture modeling: comment on Bauer
      and Curran (2003).
AB  - This commentary discusses the D. J. Bauer and P. J. Curran (2003) investigation
      of growth mixture modeling. Single-class modeling of nonnormal outcomes is
      compared with modeling with multiple latent trajectory classes. New statistical
      tests of multiple-class models are discussed. Principles for substantive
      investigation of growth mixture model results are presented and illustrated by an
      example of high school dropout predicted by low mathematics achievement
      development in Grades 7-10.

PMID- 14596498
TI  - A realistic perspective on pattern representation in growth data: comment on
      Bauer and Curran (2003).
AB  - D. J. Bauer and P. J. Curran (2003) cautioned that results obtained from growth
      mixture models may sometimes be inaccurate. The problem they addressed occurs
      when a growth mixture model is applied to a single, general population of
      individuals but findings incorrectly support the conclusion that there are 2
      subpopulations. In an artificial sampling experiment, they showed that this can
      occur when the variables in the population have a nonnormal distribution. A
      realistic perspective is that although a healthy skepticism to complex
      statistical results is appropriate, there are no true models to discover.
      Consequently, the issue of model misspecification is irrelevant in practical
      terms. The purpose of a mathematical model is to summarize data, to formalize the
      dynamics of a behavioral process, and to make predictions. All of this is
      scientifically valuable and can be accomplished with a carefully developed model,
      even though the model is false.

PMID- 14596499
TI  - The Swedish Council on Technology Assessment in Health Care (SBU) systematic
      overview of radiotherapy for cancer including a prospective survey of
      radiotherapy practice in Sweden 2001--summary and conclusions.
AB  - A systematic assessment of radiotherapy for cancer was conducted by The Swedish
      Council on Technology Assessment in Health Care (SBU) and published in 1996. The
      assessment reviewed the scientific literature up to 1993 on the use of
      radiotherapy in the treatment of solid tumours, and estimated the costs
      associated with radiotherapy. It also described the current practise of
      radiotherapy in Sweden 1992 and compared practise with scientific knowledge. The
      SBU has now conducted a follow-up study on radiotherapy for cancer, including a
      review of the scientific literature from 1994 and a prospective survey of
      radiotherapy practise in Sweden 2001. The following conclusions were drawn: The
      role of radiotherapy as an important form of treatment for cancer with both
      curative and palliative intent has been further confirmed. The use of
      radiotherapy in Sweden has increased and is now at the internationally
      recommended level. Radiotherapy in Sweden is mostly given in accordance with the
      scientific evidence but may still be underutilized in certain situations. The
      resources for radiotherapy are being utilized more efficiently. The costs of
      radiotherapy are still 5% of the total cost of cancer care, while the cost of an
      individual treatment (fraction) has decreased. The need for radiotherapy capacity
      will increase. In addition, half of the treatment equipment will have to be
      replaced in the next few years.

PMID- 14596500
TI  - Radiotherapy and cancer care in Sweden.
AB  - A systematic assessment of radiotherapy for cancer was conducted by The Swedish
      Council on Technology Assessment in Health Care (SBU) in 2001. It included an
      overview of the organisation of radiotherapy and cancer care in Sweden and
      education of staff. It further included an update of cancer statistics for Sweden
      and an estimate of the need for radiotherapy resources by the year 2010. The
      following conclusions were drawn: Compared with a similar assessment in 1992, the
      number of departments of oncology at the county hospital level has increased by
      one, and one more department was scheduled to start radiotherapy during 2002. The
      speciality of oncology in Sweden includes all types of non-surgical cancer
      treatment, in contrast to the situation in most countries, where radiation
      oncology and medical oncology are independent specialities. Gynaecologic oncology
      is a unique speciality for Sweden. The number of new cancer cases increased by
      13% between 1990 and 2000, and continues to increase by more than 1.0% per year.
      The projections of cancer incidence stated in the previous report were checked
      against observed data for the year 2000 and found to be an underestimation. To
      maintain the current capacity for radiotherapy in relation to number of new
      cancer cases by the year 2010, a total of 65 accelerators would be needed.

PMID- 14596501
TI  - Radiotherapy techniques in current use in Sweden.
AB  - A systematic assessment of radiotherapy for cancer was conducted by The Swedish
      Council on Technology Assessment in Health Care (SBU) in 2001. The assessment
      included a review of radiotherapy techniques in current use in Sweden. The
      following conclusions were drawn: Radiotherapy demands adequate knowledge of
      diagnostic methods, anatomy, cancer biology and of the physical and biological
      properties of ionizing radiation. Well-functioning teamwork on the part of the
      oncologist, medical physicist and oncology nurse is important. Radiotherapy has a
      high degree of technical sophistication, including the use of computers, which
      necessitates expert technical support. Technical development is rapid, and since
      the previous report, multileaf collimators and electronic portal imaging have
      been introduced in the clinical routine. The use of brachytherapy for treatment
      of non-gynaecological malignancies is rapidly increasing. The need for quality
      assurance in all steps of the radiotherapy procedure is stressed. A critical
      review of the literature on intraoperative radiotherapy is also included as an
      Appendix.

PMID- 14596502
TI  - A prospective survey of radiotherapy practice 2001 in Sweden.
AB  - A prospective survey of radiotherapy practice in Sweden was conducted during 12
      weeks in the autumn of 2001. All hospitals that provided radiotherapy
      participated, and all patients who started radiotherapy during the study period
      were included. The final patient sample comprised 5,105 treatments given to 4,171
      patients. The results were compared with those of a similar survey conducted in
      1992, and the following conclusions were drawn: A substantial increase in the use
      of radiotherapy was noted; The estimated proportion of cancer cases receiving
      radiotherapy (compared to the incident number of cases) had increased from 32% in
      1992 to 47%; The proportion of cancer patients receiving radiotherapy was
      estimated at between 37 and 46%; 54% of treatments were given with curative
      intent, a small increase since 1992; The difference between regional and county
      departments for proportion of treatments with curative intent had diminished;
      Treatments with curative intent used a higher proportion of resources measured in
      terms of fractions; The proportion of palliative treatment was slightly lower
      than in 1992, but the absolute number of treatments had increased by more than
      20%; No improvement in participation in clinical trials was noted; Treatments
      given with curative intent were more complex with more fields; Hyperfractionation
      was used, mainly in treatments of cancers of the head and neck, lung, and
      bladder; The use of brachytherapy for non-gynaecological malignancies had
      increased dramatically; Treatment of bone metastases with a single or few
      fractions was used much more frequently; Dose planning and patient set-up showed
      a high standard but quality control of dosimetry of given treatment did not fully
      comply with Swedish and European recommendations; The treatment devices seem to
      be used more efficiently.

PMID- 14596503
TI  - Costs of radiotherapy.
AB  - A systematic assessment of radiotherapy for cancer was conducted by The Swedish
      Council on Technology Assessment in Health Care (SBU) in 2001. The assessment
      included an overview of the capacity for radiotherapy in terms of infrastructure
      of cancer care and an estimation of the costs of radiotherapy in Sweden. A postal
      questionnaire distributed to all 16 centres of radiotherapy in Sweden showed the
      following results: In 2000 there were 57 accelerators with complementary
      equipment in operation, 24 of which had been installed 10 or more years ago
      earlier. The total cost of external radiation therapy was estimated at SEK 427
      million in the year 2000, or approximately 5% of the estimated total cost of
      oncology care in Sweden. The total cost of brachytherapy was estimated at SEK 43
      million or about one-tenth of that of external radiotherapy. The total cost of
      external radiotherapy has increased since the last inquiry (1991) by about 16%
      more than the general inflation in Sweden, but at the same time the volume of
      fractions has increased by about 37%. Thus, an increase in the efficiency of
      external radiotherapy, calculated per fraction, was achieved in the 1990s. At the
      department level, there was a clear correlation between cost of salaries and
      output of fractions of external radiotherapy, thus indicating the adaptation of
      manpower to the volume of patients. There was an even higher correlation between
      the number of accelerators and the volume of fractions of radiotherapy, which
      suggests the occurrence of certain economies of scale in Swedish external
      radiotherapy.

PMID- 14596504
TI  - Radiotherapy practices in Sweden compared to the scientific evidence.
AB  - A systematic assessment of radiotherapy for cancer was conducted by The Swedish
      Council on Technology Assessment in Health Care (SBU) in 2001. The assessment
      included a critical review of the literature on radiotherapy for cancer published
      in 1994-2001 and a prospective survey of radiotherapy practice in Sweden during
      12 weeks in the autumn of 2001. The results of the survey were compared with the
      evidence derived from the scientific literature, and the following conclusions
      could be drawn: Radiotherapy is currently given to approximately 47% of new
      cancer cases This figure is on a par with rates reported from other countries.
      For most tumour types, curative radiotherapy practices in Sweden are generally
      supported by the literature. Interstitial brachytherapy has been included in the
      treatment of non-gynaecological malignancies, and prostate cancer is now the most
      common indication. Palliative radiotherapy has increased and is today given in a
      more rational way using single or few fractions However, it still seems to be
      under-utilized in Sweden. The need for radiotherapy can be expected to increase
      until the year 2010.

PMID- 14596505
TI  - Developments in radiotherapy.
AB  - A systematic assessment of radiotherapy for cancer was conducted by The Swedish
      Council on Technology Assessment in Health Care (SBU) in 2001. The assessment
      included a review of future developments in radiotherapy and an estimate of the
      potential benefits of improved radiotherapy in Sweden. The conclusions reached
      from this review can be summarized as: Successively better knowledge is available
      on dose-response relationships for tumours and normal tissues at different
      fractionation schedules and treated volumes. Optimization of dose levels and
      fractionation schedules should improve the treatment outcome. Improved treatment
      results may be expected with even more optimized fractionation schedules. The
      radiosensitivity of the tumour is dependent on the availability of free oxygen in
      the cells. The oxygen effect has been studied for a long time and new knowledge
      has emerged, but there is still no consensus on the best way to minimize its
      negative effect in the treatment of hypoxic tumours. Development in imaging
      techniques is rapid, improving accuracy in outlining targets and organs at risk.
      This is a prerequisite for advanced treatment planning. More accurate treatment
      can be obtained using all the computer techniques that are successively made
      available for calculating dose distributions, controlling the accelerator and
      multileaf collimator (MLC) and checking patient set-up. Optimized treatment plans
      can be achieved using inverse dose planning and intensity modulation radiation
      therapy (IMRT). Optimization algorithms based on biological data from clinical
      trials could be a part of future dose planning. New genetic markers might be
      developed that give a measure of the radiation responsiveness of tumours and
      normal tissue. This could lead to more individualized treatments. New types of
      radiation sources may be expected: protons, light ions, and improved beams (and
      compounds) for boron neutron capture therapy (BNCT). Proton accelerators with
      scanned-beam systems and energy modulation give good dose distribution. The
      results reported with carbon ions from Japan and Germany are promising. An
      interesting development is to verify the dose and position for the irradiated
      volume with PET on line. Safer margins are obtained and the treatment volume can
      thus be limited. Very large accelerators are needed to accelerate the carbon
      ions. Still, it should be possible to keep the costs per patient at the same
      level as those for other types of advanced radiotherapy, since far fewer
      treatments per patient are needed. It might also be possible to treat new groups
      of patients. Increased resources are needed to introduce all the currently
      available techniques. New types of particle accelerators require large
      investments and a new structure of radiotherapy in Sweden.

PMID- 14596506
TI  - A systematic overview of radiation therapy effects in head and neck cancer.
AB  - A systematic review of radiation therapy trials in several tumour types was
      performed by The Swedish Council of Technology Assessment in Health Care (SBU).
      The procedures for evaluation of the scientific literature are described
      separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on
      radiation therapy for head and neck cancer is based on data from 39 randomized
      trials and 1 meta-analysis. In total, 40 scientific articles are included,
      involving 20893 patients. The results were compared with those of a similar
      overview from 1996 including 79 174 patients. The conclusions reached can be
      summarized as follows: General, non-nasopharynx. Substantial evidence indicates
      that the tumour effect of radiotherapy can be increased by the concomitant
      administration of chemotherapeutic agents, particularly cisplatin and 5
      fluorouracil. There is moderate evidence of a survival benefit of radiation
      combined with concomitant chemotherapy compared to radiation alone. However, the
      results are equivocal. There is substantial evidence in published studies for an
      increased frequency of severe acute side effects as a result of concomitant
      chemotherapy and radiotherapy. There are very few studies that allow any
      estimates of the risk for serious late side effects. There is a weak indication
      of an increased risk for serious fibrosis. COMMENT: The general quality of
      studies and the lack of information on serious side effects indicate a need for
      large, well-designed clinical studies with a reasonable follow-up. Larynx
      preservation studies. There is strong evidence that larynx preservation is
      possible in 50% of the patients surviving for 5 years with hypopharyngeal cancers
      when treated with neoadjuvant chemotherapy and radical radiotherapy There is a
      non-significant trend for the overall survival being lower in non-surgically
      treated patients than in those treated with primary surgery and postoperative
      radiotherapy Nasopharynx. There is moderate evidence that patients with
      nasopharyngeal carcinomas of the endemic type benefit from therapy with a
      combination of chemotherapy and radical radiotherapy. However, the results from
      the reported studies are equivocal. There is some indication that the acute side
      effects of radiation are more severe in the concomitant setting than in the
      neoadjuvant. COMMENT: There are no data on serious late toxicity. Dose,
      fractionation schedules. There is some evidence that certain schedules of altered
      fractionation improve tumour control without increasing severe late side effects.
      There is some evidence that nervous tissues are more susceptible to damage by
      altered fractionation. Solid data shows that altered fractionation increases
      acute side effects. There is moderate evidence that accelerated
      hyperfractionation may reduce the frequency of serious late side effects while
      retaining a similar tumour effect as conventional radiotherapy Hypoxic cell
      sensitizers. Most reported trials reject the usefulness of nitroimidazole
      derivatives for sensitization of hypoxic tumour cells. There is some evidence
      that patients with tumours in the pharynx and larynx may benefit from
      sensitization by nimorazole. Prophylactic treatment of side effects. There is
      weak evidence that local antibiotics have a clinically significant effect in
      preventing acute radiotherapy side effects. There is insufficient evidence that
      radioprotective agents offer clinically significant protection of parotid glands
      (one study in two publications). There is insufficient evidence that
      radioprotective agents do not spare tumour tissue. Since the previous report no
      randomized studies comparing the effectiveness of external beam radiotherapy and
      brachytherapy have been performed. Both methods are well established and have
      independently proved to be effective in the treatment of certain head and neck
      cancers. No conclusion can be drawn regarding their relative effectiveness. Since
      the previous report no data to guide the use of intraoperative radiotherapy have
      been identified.

PMID- 14596507
TI  - A systematic overview of radiation therapy effects in oesophageal cancer.
AB  - A systematic review of radiation therapy trials in several tumour types was
      performed by The Swedish Council of Technology Assessment in Health Care (SBU).
      The procedures for evaluation of the scientific literature are described
      separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on
      radiation therapy for oesophageal cancer is based on data from 42 randomized
      trials and 2 meta-analyses. A total of 44 scientific articles are included,
      involving 5 772 patients. The conclusions reached can be summarized as follows:
      There is fairly strong evidence that preoperative radiotherapy does not improve
      the survival in patients with potentially resectable oesophageal cancer. There is
      moderate evidence that preoperative chemo-radiotherapy has no beneficial impact
      on the survival of patients with potentially resectable oesophageal cancer. There
      is no scientific evidence that postoperative radiotherapy improves survival in
      patients with resectable oesophageal cancer. The documentation is, however, poor,
      consisting of only three randomized trials. There is fairly strong evidence that
      concomitant (but not sequential) chemo-radiotherapy gives significantly better
      survival rate than radiotherapy alone in inoperable oesophageal cancer. The
      results of the reported clinical trials are, however, conflicting, and no solid
      conclusion can be drawn. Hyperfractionated radiotherapy has been compared with
      conventionally fractionated radiotherapy in two randomized studies with
      conflicting results and no firm conclusion can be drawn.

PMID- 14596508
TI  - A systematic overview of radiation therapy effects in rectal cancer.
AB  - A systematic review of radiation therapy trials in several tumour types was
      performed by The Swedish Council of Technology Assessment in Health Care (SBU).
      The procedures for evaluation of the scientific literature are described
      separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on
      radiation therapy for rectal cancer is based on data from 42 randomized trials
      and 3 meta-analyses. Moreover, data from 36 prospective studies, 7 retrospective
      studies and 17 other articles were used. A total of 131 scientific articles are
      included, involving 25 351 patients. The results were compared with those of a
      similar overview from 1996 including 15 042 patients. The conclusions reached can
      be summarized thus: The results after rectal cancer surgery have improved during
      the past decade. It is likely that local failure rates after 5 years of follow-up
      at hospitals adopting the TME-concept (TME = total mesorectal excision) have
      decreased from about 28% to 10-15%. Preoperative radiotherapy at biological
      effective doses above 30 Gy decreases the relative risk of a local failure by
      more than half (50-70%). Postoperative radiotherapy decreases the risk by 30-40%
      at doses that generally are higher than those used preoperatively. There is
      strong evidence that preoperative radiotherapy is more effective than
      postoperative. There is moderate evidence that preoperative radiotherapy
      significantly decreases the local failure rate (from 8% to 2% after 2 years) also
      with TME. There is strong evidence that preoperative radiotherapy improves
      survival (by about 10%). There is no evidence that postoperative radiotherapy
      improves survival. There is some indication that survival is prolonged when
      postoperative radiotherapy is combined with concomitant chemotherapy.
      Preoperative radiotherapy at adequate doses can be given with low acute toxicity.
      Higher, and unacceptable acute toxicity has been seen in some preoperative
      radiotherapy trials using suboptimal techniques. Postoperative radiotherapy can
      also be given with acceptable acute toxicity. The long-term consequences of
      radiotherapy appear to be limited with adequate radiation techniques, although
      they have been less extensively studied. Longer follow-up periods are needed
      before firm conclusions can be drawn. Peroperative radiotherapy, preferably
      preoperative since it is more effective, is routinely recommended for most
      patients with rectal cancer since it can substantially decrease the risk of a
      local failure and increases survival. In a primarily non-resectable tumour,
      preoperative radiotherapy can cause tumour regression allowing subsequent radical
      surgery. This therapy is routinely indicated. Whether radiochemotherapy is more
      efficient than radiotherapy alone is not clear, since the results of four small
      randomized trials are partly conflicting. Preoperative radiotherapy, frequently
      combined with chemotherapy, has been used to increase the chances of sphincter
      preserving surgery in low-lying tumours. The literature is inconclusive with
      respect to how frequently this occurs. Radiotherapy frequently produces symptom
      relief in patients with rectal cancer not amendable to surgery.

PMID- 14596509
TI  - A systematic overview of radiation therapy effects in non-small cell lung cancer.
AB  - A systematic review of radiation therapy trials in several tumour types was
      performed by The Swedish Council of Technology Assessment in Health Care (SBU).
      The procedures for evaluation of the scientific literature are described
      separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on
      radiation therapy for non-small cell lung cancer (NSCLC) is based on data from 4
      meta-analyses and 31 randomized trials. Moreover, data from 12 prospective
      studies, 12 retrospective studies and 6 other articles were used. In total, 65
      scientific articles are included, involving 18 310 patients. The results were
      compared with those of a similar overview from 1996 including 28 172 patients.
      The conclusions reached can be summarized as follows: Extensive clinical
      experience indicates that radiotherapy for medically inoperable patients or
      patients refusing surgery with NSCLC stage I/II prolongs survival, 15 -20% of
      these patients reaching long-term (5-year) survival. However, no randomized
      trials have addressed this issue. There is strong evidence that postoperative
      radiotherapy in radically resected stage I/II NSCLC does not prolong survival
      compared with observation alone. There is some evidence that continuous
      hyperfractionated accelerated radiotherapy (CHART) is associated with increased
      survival compared to conventional radiotherapy in locally advanced NSCLC and also
      in medically unfit patients with stage I/II NSCLC. However, the benefit is
      limited to squamous cell histology. There is strong evidence that combined
      modality treatment with platinum-based chemotherapy and radiotherapy, either
      neoadjuvant or concomitant, is superior to radiotherapy alone in terms of
      survival in locally advanced unresectable NSCLC and should be the standard of
      care in patients with good performance status. There is some evidence that
      concomitant chemo-radiotherapy is associated with increased survival compared
      with sequential chemo-radiotherapy, albeit at the price of increased toxicity
      Comment: Combined chemo-radiotherapy of primary non-resectable stage III NSCLC
      followed by surgery in responders lacks evidence from prospective randomized
      trials and cannot be recommended for routine use. There is strong evidence that
      radiotherapy can palliate symptoms associated with the intrathoracic tumour
      burden. There is some evidence that two large fractions may be as effective as
      conventional schedules consisting of 10-13 smaller fractions in terms of
      palliation of symptoms. There is some evidence that endobronchial brachytherapy
      for palliation of symptoms associated with endobronchial tumours is not superior
      to external beam radiotherapy.

PMID- 14596510
TI  - A systematic overview of radiation therapy effects in soft tissue sarcomas.
AB  - A systematic review of radiation therapy trials in several tumour types was
      performed by The Swedish Council of Technology Assessment in Health Care (SBU).
      The procedures for evaluation of the scientific literature are described
      separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on
      radiation therapy for soft tissue sarcomas (STS) is based on data from five
      randomized trials. Moreover, data from 6 prospective studies, 25 retrospective
      studies and 3 other articles were used. In total, 39 scientific articles are
      included, involving 4 579 patients. The results were compared with those of a
      similar overview from 1996 which included 3 344 patients. The conclusions reached
      can be summarized as follows: The well-established prognostic factors for tumour
      related death from STS-histological grade, tumour size and age-are well
      documented. The importance of superficial versus deep site as well as the
      anatomic site is also reaffirmed to some extent. There is strong evidence that
      adjuvant radiotherapy improves the local control rate in combination with
      conservative surgery in the treatment of STS of extremities and trunk in patients
      with negative, marginal or minimal microscopic positive surgical margins. A local
      control rate of 90% has been achieved. Improvement is obtained with radiotherapy
      added in the case of intralesional surgery, but the local control rate is
      somewhat lower. More studies are needed on this issue. For STS in other anatomic
      sites, retroperitoneum, head and neck, breast and uterus, there is only weak
      indication of a benefit for the local control rate, with the use of adjuvant
      radiotherapy. There is still insufficient data to establish that preoperative
      radiotherapy is favourable compared to postoperative radiotherapy for local
      control in patients presenting primarily with large tumours. One small study has
      shown a possible survival benefit for preoperative radiotherapy. There is fairly
      good evidence to suggest that the preoperative setting results in more wound
      complications. There is no randomized study comparing external beam radiotherapy
      and brachytherapy. The data suggest that external beam radiotherapy and low dose
      rate brachytherapy result in comparable local control for high-grade tumours.
      Some patients with low-grade soft tissue sarcomas benefit from external beam
      radiotherapy in terms of local control. Brachytherapy with low dose rate for low
      grade tumours seems to be of no benefit, but data are sparse. The available data
      are inconclusive concerning the effect of intraoperative high dose rate
      radiotherapy for retroperitoneal STS. Further studies are needed. Neutron
      radiotherapy might be beneficial for patients with low- and intermediate-grade
      tumours considered inoperable and for those operated with intralesional margins.
      More severe side effects for neutrons have been registered. In two small studies
      investigating hyperfractionation schedules there was no indication of
      improvements compared to daily fractions of 2 Gy. Further studies should be
      encouraged. One small study using preoperative limb perfusion with TNF alpha
      melphalan and +/- interferon gamma combined with postoperative radiotherapy in
      the case of marginal or positive surgical margin has shown excellent local
      control without enhanced morbidity.

PMID- 14596511
TI  - A systematic overview of radiation therapy effects in breast cancer.
AB  - A systematic review of radiation therapy trials in several tumour types was
      performed by The Swedish Council of Technology Assessment in Health Care (SBU).
      The procedures for evaluation of the scientific literature are described
      separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on
      radiation therapy for breast cancer is based on data from 29 randomized trials, 6
      meta-analyses and 5 retrospective studies. In total, 40 scientific articles are
      included, involving 41 204 patients. The results were compared with those of a
      similar overview from 1996 including 285 982 patients. The conclusions reached
      can be summarized as follows: There is strong evidence for a substantial
      reduction in locoregional recurrence rate following postmastectomy radiation
      therapy to the chest wall and the regional nodal areas. There is strong evidence
      that postmastectomy radiation therapy increases the disease-free survival rate.
      There are conflicting data regarding the impact of postmastectomy radiotherapy
      upon overall survival. There is strong evidence that breast cancer specific
      survival is improved by postmastectomy radiotherapy. There is strong evidence for
      a decrease in non-breast cancer specific survival after postmastectomy
      radiotherapy. There is some evidence that overall survival is increased by
      optimal postmastectomy radiation therapy. There is strong evidence that
      postmastectomy radiotherapy in addition to surgery and systemic therapy in mainly
      node-positive patients decreases local recurrence rate and improves survival.
      There is moderate evidence that the decrease in non-breast cancer specific
      survival is attributed to cardiovascular disease in irradiated patients. There
      are conflicting data whether breast conservation surgery plus radiotherapy is
      comparable to modified radical mastectomy alone in terms of local recurrence
      rate. There is strong evidence that breast conservation surgery plus radiotherapy
      is comparable to modified radical mastectomy alone in terms of disease-free
      survival and overall survival. There is strong evidence that postoperative
      radiotherapy to the breast following breast conservation surgery results in a
      statistically and clinically significant reduction of ipsilateral breast
      recurrences followed by diminished need for salvage mastectomies. There is strong
      evidence that the omission of postoperative radiotherapy to the breast following
      breast conservation surgery has no impact on overall survival. In one meta
      analysis including three randomized studies a survival advantage is demonstrated
      by Bayesian statistics. There is strong evidence that the addition of a radiation
      boost after conventional radiotherapy to the tumour bed after breast conservation
      surgery significantly decreases the risk of ipsilateral breast recurrences but
      has no impact on overall survival after short follow-up. There is strong evidence
      for the use of postoperative radiotherapy to the breast following breast
      conservation surgery for DCIS (ductal breast cancer in situ). Radiotherapy leads
      to a clinically and statistically significant reduction of both non-invasive and
      invasive ipsilateral breast recurrences. There is insufficient evidence to define
      the optimal integration of systemic adjuvant therapy and postoperative
      radiotherapy. There are limited data on radiotherapy-related morbidity in breast
      cancer. No conclusions can be drawn.

PMID- 14596512
TI  - A systematic overview of radiation therapy effects in cervical cancer (cervix
      uteri).
AB  - A systematic review of radiation therapy trials in several tumour types was
      performed by The Swedish Council of Technology Assessment in Health Care (SBU).
      The procedures for evaluation of the scientific literature are described
      separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on
      radiation therapy for cervical cancer is based on data from 1 meta-analysis and
      34 randomized trials. In total, 35 scientific articles are included, involving 7
      952 patients. The results were compared with those of a similar overview from
      1996 including 34 024 patients. The conclusions reached can be summarized in
      these points: There are limited scientific data supporting that postoperative
      pelvic radiotherapy improves disease-free survival in early cervical cancer. No
      firm conclusion can be drawn. There is moderate scientific evidence that external
      beam radiotherapy combined with brachytherapy gives a similar disease-free and
      overall survival rate as radical hysterectomy in early cervical cancer. There is
      strong scientific evidence that concomitant radiochemotherapy improves disease
      free and overall survival compared to radiotherapy alone in early cervical
      cancer. The NCI has recently published an announcement stating that cisplatin
      based chemotherapy should be used concomitantly with radiotherapy in cervical
      cancer. No solid documentation for this statement can be found concerning locally
      advanced stages ( >IIB). There is a strong scientific evidence that cisplatin
      based chemotherapy given concomitantly with radiotherapy is superior to
      concomitant chemotherapy with hydroxyurea. There is no scientific evidence to
      show that neoadjuvant chemotherapy followed by radiotherapy improves disease-free
      or overall survival compared to radiotherapy alone in patients with localized
      cervical cancer. There is moderate scientific evidence that high-dose-rate
      brachytherapy gives the same local control rate as low-dose-rate brachytherapy
      but with fewer rectal complications.

PMID- 14596513
TI  - A systematic overview of radiation therapy effects in uterine cancer (corpus
      uteri).
AB  - A systematic review of radiation therapy trials in several tumour types was
      performed by The Swedish Council of Technology Assessment in Health Care (SBU).
      The procedures for evaluation of the scientific literature are described
      separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on
      radiation therapy for uterine cancer is based on data from one randomized study.
      Moreover, data from two prospective studies and seven retrospective studies were
      used. In total, 10 scientific articles are included, involving 3,446 patients.
      The results were compared with those of a similar overview from 1996 including 13
      597 patients. The conclusions reached can be summarized as: There is fairly good
      evidence that there is no need for adjuvant radiotherapy in patients with good
      risk uterine cancer. There is fairly good evidence that adjuvant radiotherapy
      reduces the relapse rate in high-risk patients but has no impact on survival.
      There is substantial documentation showing that medically inoperable patients and
      patients with locally recurrent uterine cancer can be treated with radiotherapy
      alone with curative effect.

PMID- 14596514
TI  - A systematic overview of radiation therapy effects in ovarian cancer.
AB  - A systematic review of radiation therapy trials in several tumour types was
      performed by The Swedish Council of Technology Assessment in Health Care (SBU).
      The procedures for evaluation of the scientific literature are described
      separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on
      radiation therapy for ovarian cancer is based on data from six randomized trials.
      Moreover, data from one prospective study and three retrospective studies were
      used. In total, 10 scientific articles are included, involving 1 282 patients.
      The results were compared with those of a similar overview from 1996 including
      15042 patients. The conclusions reached can be summarized in the following
      points: There is no scientific documentation supporting adjuvant radiotherapy for
      early-stage, low-risk patients. No studies have been reported where adjuvant
      radiotherapy has been compared with no adjuvant therapy in early-stage, high-risk
      patients. Adjuvant radiotherapy, either whole abdominal irradiation or
      intraperitoneal p32, has been compared with adjuvant chemotherapy in early-stage,
      high-risk patients. There is no scientific evidence to show that there is a
      difference in efficacy. There is some evidence to suggest that adjuvant
      radiotherapy after radical surgery leads to an increase in disease-free survival
      rate for patients with advanced-stage ovarian cancer. There is little
      documentation on long-term side effects (second malignancy) after adjuvant
      radiotherapy and no conclusions can be drawn.

PMID- 14596515
TI  - A systematic overview of radiation therapy effects in urinary bladder cancer.
AB  - A systematic review of radiation therapy trials in several tumour types was
      performed by The Swedish Council of Technology Assessment in Health Care (SBU).
      The procedures for evaluation of the scientific literature are described
      separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on
      radiation therapy for urinary bladder cancer is based on data from 3 meta
      analyses and 33 randomized trials. The studies include 4333 patients. The results
      were compared with those of a similar overview from 1996 including 15,042
      patients. The conclusions reached can be summarized as these points: There is
      moderate evidence for an overall survival benefit with preoperative radiotherapy
      followed by cystectomy compared to curative radiotherapy based on early studies
      (1964-1986). Since that time surgical as well as radiation techniques have
      developed considerably. Therefore, the conclusion may not be relevant to modern
      treatment of invasive urinary bladder carcinoma. There is only one small study
      reporting on curative radiotherapy where increased dose per fraction is compared
      with conventionally fractionated radiotherapy to the same total dose. Thus, no
      conclusions can be drawn concerning optimal fraction dose. A meta-analysis based
      on two studies on hyperfractionated radiotherapy gives moderate evidence of a
      survival benefit at 5 and 10 years and an increased local control rate compared
      with conventional fractionation. The documentation of local control and overall
      survival rate after split-course radiation treatment compared to continuous
      therapy is conflicting. No firm conclusions can be drawn. Four small and early
      studies have compared radiation treatment using neutrons with photon treatment.
      The reports favour therapy with photons with respect to overall treatment
      results. There is moderate evidence for this conclusion. There is fairly strong
      evidence in early studies that radiation treatment in combination with hyperbaric
      oxygen does not confer a treatment benefit compared to radiation in normal
      atmosphere. There is no indication of a treatment benefit with the addition of
      either hyperthermia or misonidazole. A large number of phase II studies,
      suggesting an increased possibility for bladder preservation with concomitant
      chemoradiotherapy compared to radiotherapy alone, have been reviewed in a
      previous SBU report on chemotherapy. Only one small randomized study has been
      reported where concomitant chemoradiotherapy with cisplatin is compared to
      radiation alone. No conclusion on the therapeutic benefit of combined treatment
      can be drawn. Large randomized studies are needed. There is some evidence that
      preoperative radiotherapy followed by cystectomy does not confer any significant
      survival benefit compared to cystectomy alone. There is moderate evidence that
      palliative radiotherapy of invasive bladder carcinoma can rapidly induce tumour
      related symptom relief. There is moderate evidence that palliative
      hypofractionated radiotherapy, 3 fractions during one week, gives the same relief
      of symptoms as 10 fractions during 2 weeks.

PMID- 14596516
TI  - A systematic overview of radiation therapy effects in brain tumours.
AB  - A systematic review of radiation therapy trials in several tumour types was
      performed by The Swedish Council of Technology Assessment in Health Care (SBU).
      The procedures for evaluation of the scientific literature are described
      separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on
      radiation therapy for brain tumours is based on data from 9 randomized trials and
      1 meta-analysis. Moreover, data from 2 prospective studies, 3 retrospective
      studies and 4 other articles were used. In total, 19 scientific articles are
      included, involving 4,266 patients. The results were compared with those of a
      similar overview from 1996 including 11,252 patients. The conclusions reached can
      be summarized as follows: The conclusion from SBU 129/2 that curative treatment
      is not available for patients with high-grade malignant glioma (grade III and IV)
      is still valid. The survival benefit from postoperative radiotherapy compared to
      supportive care only or chemotherapy is about 3-4 months, as demonstrated in
      earlier randomized studies. Quality of life is now currently estimated and
      considered to be of major importance when reporting the outcome of treatment for
      patients with brain tumours. There is no scientific evidence that radiotherapy
      using hyper- and hypofractionation leads to longer survival for patients with
      high-grade malignant glioma than conventional radiotherapy. There is large
      documentation, but only one randomized study. There is some documentation to
      support the view that patients with grade IV glioma and poor prognosis can be
      treated with hypofractionation and with an outcome similar to that after
      conventional fractionation. A shorter treatment time should be convenient for the
      patient. Documentation of the benefit of a radiotherapy boost with brachytherapy
      is limited and no conclusion can be drawn. There is no scientific evidence that
      radiotherapy prolongs life for patients with low-grade glioma. There are some
      data supporting that radiotherapy can be used to treat symptoms in patients with
      low-grade glioma. As no controlled studies have been reported, no firm conclusion
      can be drawn.

PMID- 14596517
TI  - A systematic overview of radiation therapy effects in Hodgkin's lymphoma.
AB  - A systematic review of radiation therapy trials in several tumour types was
      carried out by The Swedish Council of Technology Assessment in Health Care (SBU).
      The procedures for evaluation of the scientific literature are described
      separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on
      radiation therapy for Hodgkin's lymphoma (HL) is based on data from 12 randomized
      trials and 2 meta-analyses. Data from 3 prospective studies, 29 retrospective
      studies and 58 other articles were also used. In total, 58 scientific articles
      are included, involving 27,280 patients. The results were compared with those of
      a similar overview from 1996 including 38,362 patients. The conclusions reached
      can be summarized thus: Solid scientific documentation shows that in patients
      with HL more than 80% in the early stages and 60-70% of younger patients in
      advanced stages of disease are now cured by the development of radiotherapy and
      combination chemotherapy. Long-term follow-up shows that after 15 to 20 years the
      mortality from HL in early and intermediate stages is exceeded by other causes of
      death, mostly secondary malignancies and cardiac deaths, especially myocardial
      infarction. Convincing data show that radiotherapy plays a major role in the
      development of solid cancers and cardiovascular disease, but no randomized trials
      have been performed. During the past decade increasing awareness of fatal long
      term sequelae has fundamentally changed treatment strategies in early and
      intermediate stages. A thorough long-term follow-up is essential to evaluate the
      effects of the modifications of the therapy. In early stages of disease extended
      field irradiation is now replaced by short periods of chemotherapy followed by
      limited radiotherapy to decrease late sequelae. This approach is strongly
      supported by early reports from randomized trials. Final results cannot be fully
      evaluated for many years. The optimal radiation dose and volume after
      chemotherapy are not defined or if irradiation is needed at all. Several studies
      are under way. In intermediate stages two recently reported randomized trials
      indicate that combined modality therapy is preferable and that involved field
      could replace extended field irradiation. It is still too early to draw any firm
      conclusions. In advanced stages, there is no evidence of any survival benefit
      from additional radiotherapy. The role of radiotherapy in the case of residual
      tumour and bulky disease still remains controversial. There is no scientific
      support for improved survival with radiotherapy in conjunction with high-dose
      chemotherapy with stem-cell support. Radiotherapy as salvage treatment might be
      an alternative in late limited nodal recurrence after initial chemotherapy.
      However, the body of knowledge is small. The role of radiotherapy in the
      treatment of HL is decreasing.

PMID- 14596518
TI  - A systematic overview of radiation therapy effects in non-Hodgkin's lymphoma.
AB  - A systematic review of radiation therapy trials in several tumour types was
      performed by The Swedish Council of Technology Assessment in Health Care (SBU).
      The procedures for evaluation of the scientific literature are described
      separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on
      radiation therapy for non-Hodgkin's lymphoma (NHL) is based on data from seven
      randomized trials. Moreover, data from 17 prospective studies, 22 retrospective
      studies and 27 other articles were used. In total, 73 scientific articles are
      included, involving 13,305 patients. The results were compared with those of a
      similar overview from 1996 including 14,137 patients. The conclusions reached can
      be summarized as follows: Indolent lymphomas. Data indicate that one-third to one
      half of patients with indolent lymphoma in stage I are cured by radiotherapy
      (follow-up more than 15 years). Addition of chemotherapy to radiotherapy does not
      indicate any improvement in overall outcome. Optimal radiation dose is not
      defined and extended field is not superior to involved field. Aggressive
      localized lymphomas. Data indicate that half of the patients in stage I are cured
      by radiotherapy alone. Although randomized and non-randomized studies favour
      combined modality treatment with chemotherapy followed by radiotherapy instead of
      radiotherapy or chemotherapy alone in localized disease, no firm conclusions can
      be drawn. Conflicting data have been published on the value of radiotherapy
      towards bulky disease and no firm conclusions can be drawn. Optimal dose for
      radiation alone or after chemotherapy has not been established. Total body
      irradiation (TBI). The value of TBI for treatment of NHL has not been proven.
      There is no proof that fractionated TBI in conjunction with high-dose
      chemotherapy is superior to chemotherapy regimens alone. Primary CNS lymphomas.
      Data show that radiotherapy induces a response of short duration and is
      associated with major neurotoxicity, especially in elderly patients. High-dose
      methotrexate therapy seems to lead to longer survival than radiotherapy alone. No
      randomized trials have been performed. There is fairly good support for primary
      chemotherapy including high-dose methotrexate followed by radiotherapy in
      patients below 60 years. To minimize the risk of neurotoxicity of combined
      modality treatment it has been proposed to use chemotherapy alone and delay
      radiotherapy for relapse, especially in patients above 60 years, or use it in
      chemotherapy-resistant disease. Optimal chemotherapy regimen is not defined and
      the role of radiotherapy remains to be determined. Head and neck lymphomas. There
      is some support for combined modality treatment with chemotherapy and
      radiotherapy for aggressive lymphomas in Waldeyer's ring with limited disease.
      There are sparse data supporting radiotherapy alone in localized indolent
      lymphomas in salivary glands. Radioimmunotherapy (RIT). Radioimmunotherapy is a
      new treatment modality with systemic radiation for patients with advanced NHL,
      where conventional external beam radiotherapy plays only a minor role. Several
      phase I and II studies with RIT have documented promising results. A variety of
      monoclonal antibodies, radionuclides and study designs with both myeloablative
      and non-myeloablative approach have resulted in high response rates in patients
      with recurrent or refractory NHL. One randomized clinical trial is published,
      showing superior therapy results with radiolabelled antibody compared with the
      corresponding unlabelled antibody.

PMID- 14596519
TI  - A systematic overview of radiation therapy effects in skeletal metastases.
AB  - A systematic review of radiation therapy trials in several tumour types was
      performed by The Swedish Council of Technology Assessment in Health Care (SBU).
      The procedures for evaluation of the scientific literature are described
      separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on
      radiation therapy for skeletal metastases is based on data from 16 randomized
      trials. Moreover, data from 20 prospective studies, 5 retrospective studies and
      22 other articles were used. A total of 63 scientific articles are included,
      involving 8051 patients. The results were compared with those of a similar
      overview from 1996 including 13,054 patients. The conclusions reached can be
      summarized as follows: Irradiation of skeletal metastases is, with few
      exceptions, a palliative treatment. There is strong evidence that radiotherapy of
      skeletal metastases gives an overall (complete and partial pain relief) in more
      than 80% of patients. There is strong evidence that the duration of pain relief
      in at least 50% of patients lasts for > or = 6 months. There is convincing
      evidence that pain relief, in terms of degree and duration, does not depend on
      the fractionation schedules applied. Irrespective of the fractionation schedule
      used at irradiation, the number of later complications, such as spinal cord
      compression or pathological fractures, at the index fields are low. There are
      some data showing that the difference in cost between single and multifraction
      treatment is small. However, these data do not permit any firm conclusions to be
      drawn. Several reports indicate that early diagnosis and early therapy of spinal
      cord compression are the two most important predictors of a favourable clinical
      outcome after radiotherapy. However, no controlled studies have been undertaken.
      When the diagnosis of spinal cord compression is late, a favourable outcome might
      depend on the radio-responsiveness of the tumour. The documentation is weak and
      no conclusions can be drawn. There is some evidence that a small proportion of
      totally paralytic patients can regain walking function after radiotherapy. There
      is strong evidence that the radionuclides 89Sr and 153Sm are efficient when they
      are used as a systemic treatment of generalized bone pain due to metastasis from
      carcinomas of the prostate and breast. Overall bone pain relief occurs in about
      60-80% of patients with a median response duration of 2-4 months. There is strong
      evidence that intravenous treatment with bisphosphonates in patients with myeloma
      and osteolytic bone metastasis due to carcinoma of the breast significantly
      decreases the number of skeleton-related events and bone pain.

PMID- 14596520
TI  - The use of the case-crossover design in a continuous common source food-borne
      outbreak.
AB  - When applicable, case-crossover studies may be quicker and cheaper to complete
      than case-control studies. Because time is a major issue in outbreak
      investigations, we evaluated the interest of this design during a continuous
      common source food-borne outbreak of salmonellosis for which the vehicle
      (hamburgers) was also implicated by environmental and laboratory investigations.
      Seventeen of the 35 cases identified in the outbreak were included in the study
      according to the availability of menu records with detailed information on food
      consumed at each meal. Food exposures during a 3-day risk period before onset of
      illness were compared to those of a control time-interval of the same duration
      that preceded the risk period by two days. Seventy-seven per cent of the cases
      (13/17) had consumed hamburgers in the three days preceding onset of illness
      compared with 29% (5/17) during the control period (P = 0.04, odds ratio = 5, 95%
      CI: 1.1-46.9). In this investigation the case-crossover design proved to be a
      useful and efficient alternative to the case-control approach. However, further
      evaluation of this design in outbreak investigation is needed.

PMID- 14596521
TI  - Virulence factors of Escherichia coli strains belonging to serogroups O127 and
      O142.
AB  - A total of 102 Escherichia coli strains belonging to serogroups O127 and O142
      were examined for genotypic and phenotypic characteristics. The most frequent
      serotypes found were O127:H21, O127:H40 and O142:H34. The virulence properties
      were evaluated by adhesion to HeLa cells and hybridization with gene probes for
      diarrhoeagenic E. coli. Most strains in the two serogroups were categorized as
      enteropathogenic E. coli, but enteroaggregative E. coli was also detected in both
      serogroups. All strains that carried the eae sequence presented the LEE region
      inserted in selC. Five ribotypes were detected in serogroup O127 and four in
      serogroup O142 and a correlation between serotypes and ribotypes was observed
      mainly in serogroup O142.

PMID- 14596522
TI  - Molecular epidemiology of group B streptococci in Ireland: associations between
      serotype, invasive status and presence of genes encoding putative virulence
      factors.
AB  - Group B streptococcal isolates (n = 159) from the three Dublin maternity
      hospitals, were serotyped and analysed for the bac, bca, hylB, pepB, and rib
      genes. The serotype distribution of the isolates was Ia, 19.5%; Ib, 18.9%; II,
      10.7%; III, 29.5%; IV, 1.9%; V, 15.1%; non-typeable, 4.4%. There was a
      statistically significant association between the serotype and invasive status
      (carriage or infection) of isolates (P < 0.005), but no significant association
      between serotype and degree of invasiveness was demonstrated. The presence or
      absence of each analysed gene was not associated with the invasive status of
      isolates. Statistically significant associations were revealed between bca and
      hylB (IS1548) (P = 0.0004) and between bac and bca (P=0.014). The bac, bca, hylB
      (IS1548) and rib genes and the numbers of tandem repeats in the bca gene showed
      significant associations with serotype. Almost 50% of serotype III isolates
      possessed at least one of the bac and bca genes and 55-65% of strains of
      serotypes Ia, Ib and II possessed the rib gene. Most serotype III isolates had
      IS1548 in their hylB genes. Serotype Ib was the only serotype in which more than
      half of the strains contained more tandem repeats in the bca gene than the
      overall mean for the GBS population studied of 7.4 repeats. These findings
      indicate that some previously reported associations between putative virulence
      factors and GBS disease require further study and clarification.

PMID- 14596523
TI  - Legionella in the veterans healthcare system: report of an eight-year survey.
AB  - The Veterans Health Administration (VHA) of the Department of Veterans Affairs
      tracks legionella disease in the system of 172 medical centres and additional
      outpatient clinics using an annual census for reporting. In fiscal year 1999,
      3.62 million persons were served by the VHA. From fiscal year 1989-1999, multiple
      intense interventions were carried out to decrease the number of cases and case
      rates for legionella disease. From fiscal year 1992-1999, the number of community
      acquired and healthcare-associated cases decreased in the VHA by 77 and 95.5%
      respectively (P = 0.005 and 0.01). Case rates also decreased significantly for
      community and healthcare-associated cases (P = 0.02 and 0.001, respectively),
      with the VHA healthcare-associated case rates decreasing at a greater rate than
      VHA community-acquired case rates (P = 0.02). Over the time of the review, the
      VHA case rates demonstrated a greater decrease compared to the case rates for the
      United States as a whole (P = 0.02). Continued surveillance, centrally defined
      strategies, and local implementation can have a positive outcome for prevention
      of disease in a large, decentralized healthcare system.

PMID- 14596524
TI  - Nasal carriage of Mycobacterium leprae DNA in healthy individuals in Lega Robi
      village, Ethiopia.
AB  - The number of registered leprosy patients world-wide has decreased dramatically
      after extensive application of WHO recommended Multiple Drug Therapy (MDT). The
      annual number of new cases has, however, been almost unchanged in several
      populations, indicating that the infection is still present at community level.
      Nasal carriage of Mycobacterium leprae DNA was studied in Lega Robi village in
      Ethiopia. MDT had been applied for more than ten years, and 718 residents over 5
      years old were eligible for the study. During the first survey nasal swab samples
      were collected from 664 (92.5%) individuals. The results of a Peptide Nucleic
      Acid-ELISA test for M. leprae DNA interpreted by stringent statistical criteria
      were available for 589 (88.7%) subjects. Thirty-five (5.9%) individuals without
      clinical signs of leprosy were positive for M. leprae DNA. Seven PCR positive
      individuals lived in a household where one or two other members were also
      positive for M. leprae DNA. During a second survey 8 (46%) of 175 interpretable
      PNA-ELISA tests were positive. Of 137 individuals tested twice, only two were
      positive on both occasions whereas 10 were PCR positive only once. The study
      confirms the widespread distribution of M. leprae DNA in healthy individuals. The
      feasibility of curbing possible transmission of subclinical infection needs
      further consideration.

PMID- 14596525
TI  - Forecasting the geographical spread of smallpox cases by air travel.
AB  - Instituting air travel restrictions to slow the geographical spread of smallpox
      cases would have significant consequences and present serious logistical
      concerns. Public health decision makers must weigh the potential benefits of such
      restrictions against their negative impact. The goal of this research is to
      provide a basic analytical framework to explore some of the issues surrounding
      the use of air travel restrictions as a part of an overall containment strategy.
      We report preliminary results of a compartmental model for the inter-city spread
      of smallpox cases resulting from US domestic air travel. Although air traffic can
      be halted within hours as was shown following the terrorist attacks of 11
      September 2001, these results suggest that the consequences of halting domestic
      air travel may not be outweighed by public health benefits.

PMID- 14596526
TI  - Socio-demographic characteristics and sex practices related to herpes simplex
      virus type 2 infection in Mexican and Central American female sex workers.
AB  - This study aimed to evaluate the relationship between HSV-2 infection and several
      socio-demographic and sexual practices of Mexican and Central American female sex
      workers (FSWs) in the Soconusco region in the State of Chiapas, Mexico. A cross
      sectional study was carried out based on a sample frame of bars where FSWs were
      active in the Soconusco region. FSWs consented to investigations and answered a
      questionnaire and provided a blood sample for specific HSV-2 antibody analysis.
      One hundred and sixteen bars were studied and 484 women were interviewed. The
      overall frequency of HSV-2 infected women was 85.7%. Variables that reflected
      exposure to HSV-2 were significantly associated with the frequency of the
      infection. Additionally, variables such as education and country of origin were
      significantly associated with HSV-2 infection. These results suggest that this
      infection is highly endemic in the Soconusco, posing a health risk for the study
      population.

PMID- 14596527
TI  - Hospitalization for respiratory syncytial virus in the paediatric population in
      Spain.
AB  - The aim of this population-based retrospective study was to determine the
      incidence of hospitalization for community-acquired, laboratory-confirmed
      respiratory syncytial virus (RSV) infection in an unselected paediatric
      population from southern Europe. The study was performed in an area with 15,700
      children aged less than 5 years attended by a single hospital. The presence of
      RSV in nasopharyngeal aspirates from children with acute respiratory infection
      treated in the hospital was investigated in four seasons (July 1996-June 2000). A
      total of 390 episodes of hospitalization for RSV infection were detected and
      83.3% of the children were aged less than 1 year old. The annual hospitalization
      rate was 37/1000 for infants aged less than 6 months and 25/1000 for those aged
      less than 1 year. During the study period, 2.5% of the infants younger than 1
      year and approximately 5% of those younger than 3 months were hospitalized for
      RSV infection. The mean length of hospital stay was 5.9 days. Seven per cent of
      the patients required admission to the intensive care unit and more than half of
      these children were aged less than 1 month. In Spain, community-acquired RSV
      infection is a highly frequent cause of hospitalization in young children,
      especially in those aged less than 1 year. Prevention of RSV infection, through
      the development of vaccines and/or other strategies, should be a public health
      priority.

PMID- 14596528
TI  - Primary human herpesvirus-6 and -7 infections, often coinciding, misdiagnosed as
      measles in children from a tropical region of Brazil.
AB  - We investigated primary human herpesvirus-6 and -7 (HHV-6, HHV-7) infections as a
      cause of rashes incorrectly diagnosed as measles in Brazilian children. Sera from
      124 patients, aged 4 months to 17 years, from the states of Rio de Janeiro and
      Espirito Santo, in whom measles, rubella and parvovirus B19 infections had been
      excluded, were studied using indirect immunofluorescence antibody avidity tests;
      38 (31%) had evidence of primary HHV-6 and/or HHV-7 infections. Twenty four
      children had primary HHV-6 infection, either recent or coincident with the rash,
      and similarly 31 had primary HHV-7 infection. Remarkably, almost half (17) of
      primary infections were dual HHV-6 and HHV-7 infections with the majority, 12
      (71%), in children less than 1 year old. HHV-7 infection occurred earlier than
      previously reported, perhaps due to socioeconomic and tropical conditions in this
      region of Brazil, and thus coincided with the HHV-6 infections. This study also
      highlights the difficulties of diagnosing a rash illness on clinical grounds
      alone.

PMID- 14596529
TI  - Serodiagnosis of Japanese encephalitis among Nepalese patients by the particle
      agglutination assay.
AB  - Japanese encephalitis (JE) is a serious health problem in the southwestern region
      of Nepal. Serological diagnostic kits for routine diagnostic use in this region
      have not been available. This study was performed to examine if the particle
      agglutination (PA) assay for Japanese encephalitis virus (JEV) IgM could be
      applicable to the samples collected in Nepal and also to evaluate the accuracy of
      clinical diagnosis of JE. One hundred and ninety-three blood samples were
      collected from the patients clinically diagnosed with JE or other infectious
      diseases in the JE-endemic, southwestern region of Nepal, in 2000. The PA assay
      was performed on these 193 serum samples and the results were compared with those
      by IgM-capture ELISA. Eighty-six samples were IgM-positive by the PA assay, and
      71 of 86 were also positive by IgM-capture ELISA (sensitivity, 99%; specificity,
      88%; positive predictive value, 0.82; negative predictive value, 0.99). These
      results suggest that the PA assay is a simple, reliable and useful diagnostic
      test to support clinical diagnosis in rural hospitals of Asia including Nepal.

PMID- 14596530
TI  - A continuing high incidence of subacute sclerosing panencephalitis (SSPE) in the
      Eastern Highlands of Papua New Guinea.
AB  - The aims of this descriptive study were to confirm the high incidence of subacute
      sclerosing panencephalitis (SSPE) previously reported from Papua New Guinea (PNG)
      and to relate SSPE to previous measles vaccination and measles illness. From
      February 1997 to April 1999 we diagnosed a total of 55 patients with SSPE at
      Goroka Base General Hospital in Eastern Highlands Province (EHP) of PNG. The
      diagnosis was based on high cerebrospinal fluid and serum measles virus antibody
      titres with progressive neurological disorder and myoclonic jerks. Of these 55
      patients 42 were from EHP, including 32 whose onset was in the 2-year period 1997
      1998. The annual incidence of SSPE in EHP in these 2 years was 98 per million
      population under 20 years of age, the highest ever reported. This incidence was
      more than ten times higher than the highest incidence in the prevaccine era
      reported from elsewhere. The mean age of onset of SSPE was 7.7 years (range 2.8
      14.8 years) and the interval between measles and the onset of SSPE, where known,
      had a mean of 5.9 years and a range of 2.5-11.1 years. Among the SSPE patients 19
      had a documented history of measles vaccination. Eight of these 19 also had
      documentation of previous measles illness; of these, seven were vaccinated after
      the development of measles and one was vaccinated 20 days before measles illness.
      Two non-SSPE children received vaccination twice which was documented and
      subsequently developed measles which was also substantiated by documentation. Two
      patients with SSPE yielded amplified nucleotide sequences of measles virus that
      were different from any of the vaccine strains. We found no evidence to implicate
      measles vaccination in the development of SSPE.

PMID- 14596531
TI  - Risk factors for infection with Giardia duodenalis in pre-school children in the
      city of Salvador, Brazil.
AB  - A cross-sectional study of 694 children aged 2 to 45 months selected from 30
      clusters throughout the city of Salvador, Bahia (pop. 2.3 million) was carried
      out as part of a longitudinal study of diarrhoea in order to identify risk
      factors for infection with Giardia duodenalis. Variables studied included three
      social and demographic factors (such as mother's education and marital status),
      five relating to the peri-domestic environment (rubbish disposal, open sewers,
      paving of the street), seven relating to the home itself (house construction,
      susceptibility to flooding, water supply and sanitation) as well as a score for
      hygiene behaviour based on structured observation. After multivariate analysis
      using a hierarchical model, only four significant risk factors were found: (a)
      number of children in the household under five years (b) rubbish not collected
      from the house (c) presence of visible sewage nearby, and (d) absence of a
      toilet. All four were significant at the 1% level.

PMID- 14596533
TI  - Distribution of Campylobacter jejuni Penner serotypes in broiler flocks 1998-2000
      in a small Danish community with special reference to serotype 4-complex.
AB  - During the period January 1998-December 2001, all Danish broiler flocks were
      monitored bacteriologically for thermophilic campylobacters and isolates were
      stored at -80 degrees C. Six neighbouring broiler farms in a small community were
      selected for detailed examination of all Campylobacter jejuni isolated (n = 180)
      from these farms during 1998-2000 using Penner serotyping and pulsed-field gel
      electrophoresis (PFGE). The area and the farms were selected according to their
      prevalence of campylobacter so that both farms with low and high frequencies of
      campylobacter positive flocks were included in the study. The frequency of
      campylobacter positive flocks on the six farms ranged from 24.5 to 72.7%. One
      hundred and eighty of the isolates were C. jejuni (included in this study), 14
      isolates were C. coli whereas 7 isolates belonged to other species but were not
      further identified. By serotyping of all C. jejuni 56 isolates (31.5%) were
      assigned to the 4-complex, 32 isolates (18.0%) to serotype 2, 12 isolates (6.7%)
      to serotype 11, and 11 isolates (6.2%) were assigned to serotype 12. In three
      farms, 4-complex was the most prevalent serotype, in one farm it was the second
      most frequently isolated serotype, while serotypes 2 and 1,44, respectively, were
      the most frequently isolated from the two remaining farms. This serotype
      distribution differed from the overall country-wide distribution where serotypes
      2 and 1,44 are the most prevalent. All serotype 4-complex isolates from the six
      selected farms were compared by PFGE to serotype 4-complex isolates from the rest
      of the country. The results showed that there was a high level of diversity among
      isolates from the whole country, whereas isolates from the six farms were very
      homogeneous and only displayed one or a few different PFGE patterns on each farm.
      It is suggested that certain campylobacter clones persist in a confined
      geographical area, probably at the farm, and that the broiler houses may be
      repeatedly infected with a few C. jejuni clones during succeeding broiler flocks.
      New clones may be introduced, however, the sources and vehicles are yet unknown.

PMID- 14596532
TI  - Blastomycosis in Missouri: epidemiology and risk factors for endemic disease.
AB  - Between 1992 and 1999, 93 cases of blastomycosis, including 25 laboratory
      confirmed cases, were identified in Missouri (annual incidence, 0.2/100,000
      population). Mississippi County in southeastern Missouri had the highest
      incidence (12/100,000) with a much higher rate among blacks than whites in this
      county (43.21/100,000). The mortality rate, 44% was also higher among blacks. To
      determine risk factors for endemic blastomycosis, a case-control study was
      conducted among southeastern Missouri residents. Independent risk factors for
      blastomycosis were black race and a prior history of pneumonia. No environmental
      exposures or socioeconomic factors were significantly associated with increased
      risk. The increased risk among blacks may possibly be related to genetic factors,
      but further studies are needed to clarify this. However, heightened awareness of
      the disease and a better understanding of the risk factors are important and may
      lead to earlier diagnosis and start of treatment, possibly improving outcome.

PMID- 14596534
TI  - Correlation between geographic distance and genetic similarity in an
      international collection of bovine faecal Escherichia coli O157:H7 isolates.
AB  - Evidence from epidemiological and molecular studies of bovine Escherichia coli
      O157:H7 suggests that strains are frequently transmitted across wide geographic
      distances. To test this hypothesis, we compared the geographic and genetic
      distance of a set of international bovine Escherichia coli O157:H7 isolates using
      the Mantel correlation. For a measure of genetic relatedness, pulsed-field gel
      electrophoresis of six different restriction enzyme digests was used to generate
      an average Dice similarity coefficient for each isolate pair. Geographic distance
      was calculated using latitude and longitude data for isolate source locations.
      The Mantel correlation between genetic similarity and the logarithm of geographic
      distance in kilometers was -0.21 (P<0.001). The low magnitude of the Mantel
      correlation indicates that transmission over long distances is common. The
      occurrence of isolates from different continents on the same cluster of the
      dendrogram also supports the idea that Escherichia coli O157:H7 strains can be
      transferred with considerable frequency over global distances.

PMID- 14596535
TI  - Diversity and stability of the Staphylococcus intermedius flora in three bitches
      and their puppies.
AB  - The study investigated the transfer and the stability of the S. intermedius flora
      in three bitches and their puppies. A total of 240 cutaneous and mucosal isolates
      of S. intermedius was collected from three healthy Cavalier King Charles spaniels
      and their puppies during the immediate prepartum period and after whelping, over
      a total of 15 weeks. The isolates were genotyped with random amplified polymeric
      DNA-polymerase chain reaction analysis (RAPD-PCR) using two primers. Seventeen
      different genotypes of S. intermedius were identified. One or two of the
      genotypes were dominant in each of the bitches and their puppies. The rest were
      isolated only once or twice from the bitches or their puppies. The study
      indicates that S. intermedius flora within each studied bitch mainly consisted of
      one or two dominating and persistent clones, which were transferred from the dam
      to her puppies immediately after birth.

PMID- 14596536
TI  - Molecular typing of Mannheimia (Pasteurella) haemolytica serotype A1 isolates
      from cattle in Japan.
AB  - Pulsed field gel electrophoresis (PFGE) and random amplified polymorphic DNA
      (RAPD) methods were applied for molecular typing of 130 Mannheimia (Pasteurella)
      haemolytica serotype A1 isolates obtained from 13 prefectures in Japan. These
      isolates were divided into 15 ApaI PFGE profiles that formed six distinct
      clusters (clusters A-F). Fifty-three (40.7%) isolates were classified in cluster
      B, and 20.0, 13.8, 12.3, 6.9 and 6.1% of isolates were in clusters E, A, F, D and
      C, respectively. The isolates of cluster B were differentiated into seven
      subtypes (B1-B7) and subtype B5 contained 63% (34/53) of isolates. RAPD revealed
      four banding patterns (types I-IV), and among 130 isolates 60.7% (79/130) of
      isolates were RAPD type I. All of the RAPD type I isolates were grouped into
      clusters A-C by PFGE. There was no relationship between molecular typing and
      geographic origin of these isolates. These results indicate that isolates of M.
      haemolytica A1 strain with various molecular profiles have already spread in
      Japan and may have caused sporadic infections.

PMID- 14596537
TI  - Corynebacterium pseudotuberculosis infection in Israeli dairy cattle.
AB  - Two forms of Corynebacterium pseudotuberculosis infection in Israeli dairy cattle
      herds during a survey period of 13 years (1989-2001) are described. The more
      common form, which was diagnosed in 45 herds, was characterized by ulcerative
      granulomatous lesions which occurred either sporadically--in 26 herds (with a
      morbidity rate of up to 5%)--or in an epidemic course in 19 herds. Most (80.6%)
      of the affected animals were cows; the rest were first-calving cows (16.2%) and
      heifers (3.2%). The morbidity occurred mostly during the summer months. The
      ulcerative granulomatous lesions appeared in three clinical forms: cutaneous,
      mastitic and visceral. Mixed forms were also observed. The morbidity rate was
      6.4% and the culling rate reached 16.3% of the affected animals. Most of the
      strains of C. pseudotuberculosis which were isolated from the abscesses in the
      cutaneous form of the disease and from milk samples failed to reduce nitrate. A
      decrease in milk production (6%) and an increase in bulk-milk somatic cell count
      were noted. Necrotic and ulcerative dermatitis on the heel of the foot occurred
      in an epidemic course in heifers in only two herds during the winter months, with
      morbidity rates of 7.5 and 76.2%, respectively. C. pseudotuberculosis isolates
      from skin lesions and from the soil did reduce nitrate. Clinical,
      epizootiological and microbiological aspects of the infection are described.

PMID- 14596538
TI  - The infection rate of Daphnia magna by Pasteuria ramosa conforms with the mass
      action principle.
AB  - In simple epidemiological models that describe the interaction between hosts with
      their parasites, the infection process is commonly assumed to be governed by the
      law of mass action, i.e. it is assumed that the infection rate depends linearly
      on the densities of the host and the parasite. The mass-action assumption,
      however, can be problematic if certain aspects of the host-parasite interaction
      are very pronounced, such as spatial compartmentalization, host immunity which
      may protect from infection with low doses, or host heterogeneity with regard to
      susceptibility to infection. As deviations from a mass-action infection rate have
      consequences for the dynamics of the host-parasite system, it is important to
      test for the appropriateness of the mass-action assumption in a given host
      parasite system. In this paper, we examine the relationship between the infection
      rate and the parasite inoculum for the water flee Daphnia magna and its bacterial
      parasite Pasteuria ramosa. We measured the fraction of infected hosts after
      exposure to 14 different doses of the parasite. We find that the observed
      relationship between the fraction of infected hosts and the parasite dose is
      largely consistent with an infection process governed by the mass-action
      principle. However, we have evidence for a subtle but significant deviation from
      a simple mass-action infection model, which can be explained either by some
      antagonistic effects of the parasite spores during the infection process, or by
      heterogeneity in the hosts' susceptibility with regard to infection.

PMID- 14596539
TI  - Molecular epidemiological study of Brachyspira pilosicoli in Finnish sow herds.
AB  - Brachyspira (B.) pilosicoli, the causative agent of intestinal spirochaetosis in
      pigs, is a quite common laboratory finding from faecal samples of weaned and
      growing pigs in Finland. A better understanding of the epidemiology of B.
      pilosicoli in and between Finnish pig farms is needed. Altogether 131 B.
      pilosicoli isolates from 49 Finnish sow herds were studied by pulsed-field gel
      electrophoresis. MluI was used as a restriction enzyme for all the isolates, and
      SmaI for 70 isolates. The isolates were divided into 54 different
      macrorestriction profiles (MRP) by MluI. Most farms had distinct B. pilosicoli
      genotypes, and common genotypes among herds were rare. B. pilosicoli was re
      isolated after 3 years in three herds; the same MRP persisted in each of these
      herds. A genetic clustering of B. pilosicoli isolates between two major pork
      production areas was not detected.

PMID- 14596541
TI  - Leptospiral carrier state and seroprevalence among animal population--a cross
      sectional sample survey in Andaman and Nicobar Islands.
AB  - A study was conducted with the objective of assessing the leptospiral carrier
      state and seroprevalence among animal population of Andaman and Nicobar Islands.
      A total of 494 sera samples from different domestic animals and 85 samples from
      rats (Rattus rattus) were tested by microscopic agglutination test using nine
      serogroups prevalent in these islands. Antibodies to leptospires were detected in
      164 samples giving an overall seroprevalence of (33.11%). The seroprevalence was
      highest among cows (40.32%). Of 85 rat (Rattus rattus) samples tested for
      antileptospiral antibodies six (7.1%) were positive. Leptospires were isolated
      from kidney of two rats and urine of one cow. Isolate from urine of cow was
      heavily contaminated and was subsequently lost during further subculture. The two
      isolates were found to be pathogenic, belonging to serogroup Grippotyphosa. The
      isolates were further characterized by using a set of monoclonal antibodies. The
      agglutination patterns of isolates were similar to that of ratnapura and
      valbuzzi, however these did not completely match.

PMID- 14596540
TI  - The seroepidemiology of Lyme borreliosis in zoo animals in Germany.
AB  - We conducted the first seroepidemiological study to evaluate the exposure of zoo
      animals to Borrelia burgdorferi s.l. in German zoos and wildlife parks. A total
      of 1487 individuals representing 148 ungulate and carnivore species belonging to
      19 families were examined using a non-species dependent ELISA. Specific
      antibodies were detected in 154 (10.4%) animals; 168 (11.3%) sera produced
      borderline results. The percentage of seropositive individuals was related to
      species and origin (zoo), and increased with age of the animals. Sex and season
      did not influence seroprevalence. Examination of 600 ticks (Ixodes ricinus;
      caught from vegetation in the zoos) by darkfield microscopy and indirect
      immunofluorescence technique revealed infection rates within the range typical
      for Central Europe. The results substantiate that there is an infection risk for
      zoo animals. A differential diagnosis of Lyme borreliosis should be taken into
      account in case of suspicious clinical symptoms and possible contact to ticks.

PMID- 14596542
TI  - Design-based analysis of surveys: a bovine herpesvirus 1 case study.
AB  - This paper critically assesses the design implications for the analysis of
      surveys of infections. It indicates the danger of not accounting for the study
      design in the statistical investigation of risk factors. A stratified design
      often implies an increased precision while clustering of infection results in a
      decreased precision. Through pseudo-likelihood estimation and linearisation of
      the variance estimator, the design effects can be taken into account in the
      analysis. The intra-cluster-correlation can be investigated through a logistic
      random effect model and a generalised estimating equation (GEE), allowing the
      investigation of the extent of spread of infections in a herd (cluster). The
      advantage of using adaptive Gaussian quadrature in a logistic random effect model
      is discussed. Applicable software is briefly reviewed. The methods are
      illustrated with data from a bovine herpesvirus 1 (BHV-1) serosurvey of Belgian
      cattle.

PMID- 14596543
TI  - Comparison of the transmission characteristics of low and high pathogenicity
      avian influenza A virus (H5N2).
AB  - Low pathogenicity avian influenza A strains (LPAI) of the H5 and H7 type are
      noted for their ability to transform into highly pathogenic counterparts (HPAI).
      Here we compare the transmission characteristics in poultry of LPAI H5N2
      (A/Chicken/Pennsylvania/83) and corresponding HPAI virus by means of transmission
      experiments. In the experiments, five inoculated animals are placed in a cage
      with five contact animals, and the infection chain is monitored by taking blood
      samples, and samples from the trachea and cloaca. The data are analysed by final
      size methods and a generalized linear model. The results show that HPAI virus is
      more infectious and induces a longer infectious period than LPAI. In fact, fully
      susceptible animals are invariably infected when confronted with HPAI virus and
      die within six days after infection. Animals previously infected with LPAI virus,
      on the other hand, survive an infection with HPAI virus or escape infection all
      together. This implies that a previous infection with LPAI virus effectively
      reduces susceptibility of the host to infection and decreases transmission of
      HPAI virus. We discuss the implications of these conclusions for the control and
      evolution of avian influenza viruses.

PMID- 14596544
TI  - Dynamics of a scrapie outbreak in a flock of Romanov sheep--estimation of
      transmission parameters.
AB  - Knowledge of epidemiological mechanisms and parameters underlying scrapie
      transmission in sheep flocks remains very limited at present. Here we introduce a
      method for fitting stochastic transmission models to outbreak data to estimate
      bounds on key transmission parameters. We apply this method to data describing an
      outbreak of scrapie in a closed flock of Romanov sheep. The main findings are
      that the relative infectiousness of infected animals in this outbreak becomes
      appreciable early into disease incubation and that the mean incubation period is
      less than 1.5 years. We also find that the data are consistent with a broad range
      of values for the basic reproduction number R0 and describe how the boundaries of
      this range depend on assumptions about the mean incubation period and the
      contribution to transmission of a long-lived environmental reservoir of
      infectivity.

PMID- 14596545
TI  - Screening for West Nile virus infections of susceptible animal species in
      Austria.
AB  - Avian mortality and encephalomyelitis in equines are considered good indicators
      for West Nile virus (WNV) activity. We retrospectively tested 385 horse sera for
      WNV antibodies and looked for WNV nucleic acid and/or WNV antigen in paraffin
      embedded tissues from 12 horses with aetiologically unresolved encephalomyelitis
      and 102 free-living birds of different species which had been found dead. With
      the exception of four horses originating from eastern European countries
      investigated on the occasion of transit through Austria, all horse sera were
      negative. Nested RT-PCR of the horse tissues yielded no amplification of WNV-RNA.
      Also, all bird samples, examined by immunohistochemistry, in situ hybridization
      and nested RT-PCR were negative for WNV. These results indicate that currently
      WNV cannot be considered a significant pathogen in Austria.

PMID- 14596546
TI  - Etiology of cerebral palsy.
AB  - Cerebral palsy has a complex and multifactorial etiology. Approximately 5%-10% of
      cases can be ascribed to perinatal hypoxia, but the vast majority of cases are
      caused by the interplay of several risk factors and antenatal, perinatal, and
      neonatal events. The strongest risk factors include prematurity and low birth
      weight. The prevalence of cerebral palsy has remained constant despite
      improvements in obstetric and neonatal care. For a long time, the only causal
      factors explored to account for risk for cerebral palsy were complications of
      labor and delivery. As other periods have been investigated, new associations
      have come to light. The current understanding of contributors to the risk for
      cerebral palsy is still incomplete. Multiple causes may interact by way of
      excitotoxic, oxidative, or other converging pathophysiologic pathways. A single
      factor, unless present to an overwhelming degree, often may be insufficient to
      produce cerebral damage, whereas two or three interacting pathogenic assaults may
      overwhelm natural defenses and produce irreversible brain injury. The low
      prevalence of cerebral palsy makes the formal testing of preventative strategies
      difficult. There is a need for such strategies to be carefully assessed in well
      designed, multicenter, randomized, controlled trials before becoming part of
      clinical practice, however, so that the balance between harm and benefit is known
      in advance.

PMID- 14596547
TI  - General assessment of the upper limb.
AB  - Clinical examination of the upper limb of a spastic patient is a lengthy and
      somewhat complicated procedure that is best performed together with all the
      practitioners involved in the child's care. It should be repeated before any
      decision is made regarding treatment. Standard procedures in surgery of the upper
      limb in cerebral palsy are not appropriate, as the clinical picture is different
      for each individual patient. Surgery should be aimed at correcting spasticity,
      muscle/joint contracture, and motor deficit as required. All these elements
      therefore must have been assessed carefully before treatment. Finally, clinical
      examination detects all local and general contraindications to surgery and
      selects the appropriate candidates.

PMID- 14596548
TI  - Functional assessment aided by motion laboratory studies.
AB  - The physician needs to integrate the results of the assessment of overall
      patterns of functional use (Table 1), static contractures, dynamic deformities of
      motor imbalance for multiple levels of involvement (shoulder, elbow, wrist, and
      hand), and sensory deficiencies. This information is combined with a general
      assessment of the child's mentation, motivation, and generalized medical
      condition. Certain patients benefit most from surgical intervention in cerebral
      palsy. Patients with spastic deformities or flaccid control of specific movements
      can be helped significantly. In patients with flaccid control of certain
      movements, such as absent ability to extend the wrist or abduct the thumb,
      surgery is centered on tendon transfers to augment the patient's ability to
      perform that movement. In patients with excessive spasticity or musculotendinous
      contracture, surgery is centered on muscle lengthening. In general, patients with
      athetosis are not treated surgically; the only surgical treatment considered for
      the athetotic patient is fusion, as this helps preposition the limb in a desired
      position and "simplifies" the system for the patient to control. Sensibility
      deficiencies do not preclude effective tendon transfer but do limit the overall
      use of the limb; patients with sensibility deficiencies need to be coached to use
      visual input as their afferent information. Motor deficiencies can be assessed by
      observation, examination, functional testing, and motion laboratory analysis.
      Combining an assessment of shoulder, elbow, forearm, wrist, thumb, and finger
      abilities and disabilities helps provide the physician with an overall plan of
      upper limb reconstruction using soft tissue releases, tendon transfers, and joint
      stabilization procedures to address the upper limb functional deficiencies. The
      ideal candidate for tendon transfer surgery is 7 years of age or older so they
      can be cooperative with postoperative rehabilitation and motivated to improve the
      use of their limb. Children with passive use of their limb (Functional Use
      Classification levels 1-3) can be improved most, on average 2.7 levels to active
      use of their limb (Functional Use Classification levels 4-6). An overall
      treatment plan is synthesized, taking into account the child's capabilities,
      disabilities, and potential, in the context of the child's age and expectations.
      The assessment techniques discussed in this article are the first step to
      appropriate treatment.

PMID- 14596549
TI  - Casting, splinting, and physical and occupational therapy of hand deformity and
      dysfunction in cerebral palsy.
AB  - The treatment of hand deformity and associated dysfunction is a major focus of
      physical and occupational therapy for people with CP, as poor grasp and
      manipulation has potential to impact on many aspects of daily life. To assist
      therapists in analyzing patterns of movement of the wrist, finger, and thumb
      musculature at rest and during functional activities, five patterns of deformity
      commonly seen in the hypertonic hand are described. Interventions that impact on
      hypertonicity and associated contracture and that facilitate functional use of
      the hand in the presence of these deformities are discussed. The paucity of
      evidence from clinical trials on intervention strategies reflects in part the
      diversity of people with CP and the highly individual functional problems they
      encounter. While further research is needed on the many possible interventions
      and how they contribute to maximizing hand function, there is increasing evidence
      of the value of therapy that is directed to functional outcomes relevant to the
      individual.

PMID- 14596550
TI  - Pharmacologic management of the spastic and dystonic upper limb in children with
      cerebral palsy.
AB  - Spasticity or dystonia of the upper limb in children with CP commonly is seen as
      part of a more involved clinical picture. Each can cause functional problems in
      and can interfere with the quality of life of children with CP. Pharmacologic
      manipulation of the spasticity and dystonia requires a patient and ordered
      approach. Treatment often is performed using an open trial method, with
      medications introduced slowly but often being limited in their usefulness by
      significant side effects. Despite multiple medications being available for
      spasticity and dystonia management, few of the oral treatments have been assessed
      systematically in children with CP. Specific evaluation of the use of enteral
      medications in upper limb management is even rarer.

PMID- 14596551
TI  - Botulinum toxin A in the management of upper limb spasticity in cerebral palsy.
AB  - Clinical experience thus far has shown BoNT-A to be a safe and efficacious method
      in the short to medium term management of spasticity of the upper limb in
      cerebral palsy. The relaxation of hypertonic musculature allows for improvement
      in function and posture, reduction of pain, and in some patients, improvement in
      cosmesis. It is also a valuable tool in predicting response to and guiding
      contemplated muscle-tendon surgery. Careful patient selection, detailed clinical
      assessment of deformity and disability, and a clear outline of treatment goals
      are essential to good outcomes. Further work needs to be done to determine
      optimum doses of BoNT-A for individual muscles and to evaluate the long-term
      outcome of repeated injections.

PMID- 14596552
TI  - Electrical stimulation in the management of spastic deformity.
AB  - This article outlines a nonsurgical approach that includes neuromuscular
      electrical stimulation and dynamic bracing for the management of spastic
      deformity in cerebral palsy. Neuromuscular electrical stimulation is used
      commonly for lower extremity spasticity. Its clinical application in upper
      extremity spasticity, together with dynamic bracing, is a new entity providing
      predictable and quick short-term results with significant improvement in quality
      of life.

PMID- 14596553
TI  - Surgical management of the hand in infantile spastic hemiplegia.
AB  - Selected spastic patients with cerebral palsy can be helped by peripheral
      reconstructive surgery, of the upper limb. Although surgery cannot make a limb
      that was functionally poor into a perfect one, it can greatly improve the
      preoperative condition. Most poor surgical results are caused by incorrect
      selection of patients or poor execution of surgical procedures. The worst mistake
      is to perform soft tissue procedures--tendinous release or tendinous transfers-
      on a patient with pure athetosis. The results in these cases are unpredictable
      and often fail. The same concept is applied to rigidity, hypotonia, dystonia, and
      ataxia. The surgical program is organized according to the type and severity of
      the deformity (clinical groups). The goals are to correct the deformities and to
      improve the muscular balance of the hand in one surgical stage. It must be
      remembered that spastic muscle cannot be used for tendon transfer with the same
      efficiency as in patients with a flaccid paralysis. Results were satisfactory in
      92% of cases of groups I and II. If group III is included, the percentage of
      satisfactory results reduces significantly.

PMID- 14596554
TI  - The upper limb in cerebral palsy: surgical management of shoulder and elbow
      deformities.
AB  - The authors report a simple chart that offers a comprehensive picture of
      spasticity of the upper limb and provides a more objective method of recording
      data. Distinction is made between fixed postures and the residual active range of
      motion at the shoulder and elbow. The presence and function of the muscles can be
      identified easily on dynamic EMG studies, which are essential for understanding
      the degree of spasticity and dyssynergy related to a single muscle. When
      spasticity of the upper arm is managed with a global approach and objectives are
      defined clearly in advance with the patient and caregivers, treatment of shoulder
      and elbow deformities can achieve important results for personal hygiene or
      functional targets.

PMID- 14596555
TI  - Surgical management of forearm pronation.
AB  - Active volitional supination enhances upper limb function. In the spastic forearm
      with pronation deformity, careful preoperative assessment of muscle function is
      necessary to design a treatment plan to improve supination. Concomitant
      procedures performed for flexion contractures have to be taken into
      consideration. The release of the forearm, wrist, and fingers from a contracted
      pronated position may unmask active supination or may make the need for a tendon
      transfer with supinatory activity obvious.

PMID- 14596556
TI  - Surgical management of wrist and finger deformity.
AB  - The surgical results of upper extremity intervention have been shown to improve
      hand function from paperweight/passive assist function to active assist function.
      Although children with cerebral palsy commonly have a sensibility deficiency in
      conjunction with their motor deficiency, several recent studies have disproved
      the previous doctrine that hand surgery should not be performed on children with
      sensibility deficiencies. The author's report of 134 children treated surgically
      showed that preoperatively 50% had impaired two-point discrimination and 75% had
      impaired stereognosis: impaired sensibility had no adverse effect on surgical
      results. Eliasson et al reported on 32 children treated surgically with tendon
      transfers and muscle releases. Impaired sensibility before the surgery did not
      influence the outcome. In fact, Dahlin et al reported 36 patients treated
      operatively and followed for 18 months, finding an improvement in stereognosis
      function associated with the improvement in their motor function, presumably
      because of improved functional use. Children with cerebral palsy can improve
      their motor function and perhaps also their sensibility function with
      appropriately planned and executed tendon release and transfer surgery. Balance
      of the wrist and fingers is the key clement in improvement of upper limb
      function.

PMID- 14596557
TI  - Surgical management of the thumb in cerebral palsy.
AB  - Surgical treatment of the thumb in cerebral palsy is complex and treatment must
      be directed toward the specific deformities. Thumb-in-palm deformity can be
      treated successfully in patients with spastic CP, but caution is required in
      patients with other varieties of CP. The main deforming force is contracture and
      spasticity of the intrinsic thumb muscles. Treatment involves release of the
      deforming muscles and other soft tissue, augmentation of opposing muscles, and
      stabilization of appropriate joints.

PMID- 14596558
TI  - Functional and cosmetic outcome of surgery for cerebral palsy in the upper limb.
AB  - Function, cosmesis, hygiene, and ability to dress can be improved by appropriate
      surgery. This frequently involves multiple simultaneous procedures and addresses
      the muscles, their tendons, and the joints they pass over. The improvement in
      cosmesis is most profound in hemiplegic patients. Overall, patients are satisfied
      with the results of surgery.

PMID- 14596559
TI  - Brachial plexus dorsal rhizotomy in hemiplegic cerebral palsy.
AB  - Brachial plexus dorsal rhizotomy releases spasticity, improving the functional
      use of the hand. Grasping and pinch strength are augmented, together with
      movement speed and dexterity. Even when four dorsal roots have been sectioned,
      hand sensibility is largely preserved. Movement control is improved and equally
      advantageous in athetotic patients. Brachial plexus dorsal rhizotomy does not
      exclude the use of tendon lengthening or transfer procedures, but it is the
      authors' opinion that orthopedic procedures should be performed after dorsal
      rhizotomy. Children aged 5-6 years without muscle contractures are the ideal
      candidates to benefit fully from dorsal rhizotomy.

PMID- 14596560
TI  - On the astonishing clinical irrelevance of neuroscience.
AB  - The clinical work of psychoanalysts can be thought of in both a narrow and a
      broad sense. In the narrow sense, it refers to what is commonly thought of as
      psychoanalytic technique, the methods analysts use to understand their patients
      and to convey that understanding to them. In the broad sense, it refers to the
      entirety of their work as clinicians: the content of understanding, as well as
      such things as diagnosing, estimating analyzability, recommending therapy, and
      prescribing medication. The current enthusiastic expectation that neuroscience
      will have an immediate and direct impact on clinical work in the narrow sense is
      misguided, but neuroscientific discoveries, it is argued, will have a major
      impact on psychoanalytic theory in the not too distant future. The resulting
      changes in metapsychology will ultimately have reverberations on clinical work in
      the broad sense, although psychoanalytic technique, the analyst's basic approach
      to patients, will remain essentially the same.

PMID- 14596561
TI  - The emerging dialogue between psychoanalysis and neuroscience: neuroimaging
      perspectives.
AB  - Current progress in the cognitive neurosciences is highly relevant to the
      development of psychoanalytic theory and practice. Neuroscience is today becoming
      mature enough to provide empirical biological approaches for the investigation of
      psychoanalytic models and observations. The current state of functional
      neuroimaging techniques is reviewed, selected paradigms and findings relevant to
      psychotherapy research are presented, and ways to pursue the dialogue between
      psychoanalysts and neuroscientists are discussed, as are some related obstacles
      and pitfalls. The emerging dialogue between psychoanalysts and neuroscientists
      may help not only to reestablish a solid position of psychodynamic theory and
      treatment in contemporary medicine, but also to bridge the division between
      "psychological" and "somatic" treatments, and gain important insights into the
      mind-brain relationship.

PMID- 14596562
TI  - The social character of thinking.
AB  - What Freud called "the reality principle," or judgment, presumes on the part of
      the child who has arrived at judgment the implicit grasp of a complex of
      concepts: truth and falsity, belief, subjective and objective, the objectively
      real, my perspective and yours. Work in both philosophy and infant research
      points to the essential importance in the development of judgment of a
      triangulating situation that involves particular sorts of communications between
      two creatures and an external object that interests them both. In this light
      Bion's theory of thinking is critically examined and the meaning of primary
      process and fantasy is discussed.

PMID- 14596563
TI  - Ghosts of paradigms past: the once and future evolution of psychoanalytic
      thought.
AB  - An example of the psychoanalytic mode of thought is put forward concerning how
      psychoanalytic theories have historically been constituted and transformed. The
      model of world hypotheses, characterized by multiple irresolvable truth claims,
      captures the nature of most psychoanalytic theorizing until about 1970. Each of
      two world hypotheses--one grounded in intrapsychic conflict (seen when the
      analyst observes from outside the transference) and the other in interpersonal
      internalization (seen when the analyst observes from inside the bidirectional
      interactive processes)--is an autonomous and self-sufficient aggregate. The
      stance taken by the analyst-observer with respect to the analytic interaction is
      key to seeing how the two world hypotheses are made manifest in clinical work and
      in theory. By contrast, the model of competing programs captures the essential
      nature of most psychoanalytic theorizing since about 1970, and is characterized
      by the necessity of each progressively evolving through a particular kind of
      commerce with its neighbors. Such commerce is necessary when a program is in
      danger of degenerating. In this way of thinking, there is a fundamental tension
      between classical psychoanalysis adapting to the demands and exigencies of its
      particular and ever evolving historical niche and simultaneously retaining the
      core commitments that guarantee continuity. Honoring the forces of progression
      displaces the quest for truth as a paramount goal of psychoanalysis. A
      developmental lag in recognizing this transformation has hindered progress toward
      a comparative, process-centered psychoanalysis.

PMID- 14596564
TI  - Psychosomatic medicine: the divergent legacies of Freud and Janet.
AB  - A series of differing explanations of a puzzling case of psychosomatic illness
      introduces some reflections on a century's history of psychoanalytic interest in
      the mind-body problem. Freud and Janet explained the physical symptoms of
      hysteria using radically different models of the mind. Since then Janet's model,
      banished early on, has returned to haunt the castle of psychoanalysis. The
      enduring influence of Janet's model on subsequent thought in this field,
      especially that of Marty and de M'Uzan, Sifneos, LeDoux, and others, is traced,
      as is the influence of Freud's model on Groddeck, Alexander, McDougall, Fonagy,
      and others. It is argued that although these models are vastly different at one
      level of abstraction, at a higher level they share an important set of
      assumptions.

PMID- 14596565
TI  - Dissociation and the parent-infant dialogue: a longitudinal perspective from
      attachment research.
AB  - Two longitudinal attachment studies of families at social risk have now followed
      their cohorts of infants to late adolescence. Several key findings have emerged
      related to outcomes of interest to psychoanalysts. First, data from both studies
      indicate that disorganized attachment behaviors in infancy are important
      precursors of later dissociative symptomatology. Second, this early vulnerability
      is related to patterns of parent-infant affective communication, particularly
      quieter behaviors like emotional unavailability or role reversal, and does not
      appear to reside in the infant alone. Finally, the results suggest that the
      quality of the attachment relationship may in part account for why some people
      exposed to later trauma develop dissociative symptoms and others do not. To
      paraphrase Dori Laub (1993), the mother's seeing and not knowing in infancy may
      be a precondition of her child's knowing and not knowing in late adolescence. It
      remains unclear, however, whether the early relationship is predictive due
      primarily to the onset of an internal defensive process in infancy or whether its
      predictive power resides primarily in enduring patterns of parent-child dialogue
      that continually reinforce the child's segregated and contradictory mental
      contents.

PMID- 14596566
TI  - Analyzing the traumatic impact of childhood visual impairment.
AB  - Material is presented from three analyses involving the impact on adult
      functioning of childhood trauma to the visual system. The clinical process by
      which unrecognized but ongoing traumatic reactions are identified for subsequent
      analysis is described. It is of particular importance, with these patients, to
      recognize their lifelong experience of visual confusion resulting from problems
      in their visual anatomy. Only then can fantasies and affects related to these
      physically induced states of confusion be worked through. Working through these
      reactions promotes the neutralization of related primitive narcissistic affects,
      mourning, and realistic accommodation, and leads to a more intact and integrated
      sense of self, and a marked increase in self-esteem. With this newly integrated
      sense of self, the complex interaction between physically induced confusion
      states and more typical developmental conflicts with objects can be worked
      through, resulting in more realistic and intense cathexes of the external world.
      The trauma suffered by these patients had been greatly compounded by its having
      gone unrecognized. To miss this yet again in an analysis is to repeat the past
      and retraumatize the patient. These findings have clear implications for patients
      with other biologically related symptoms (e.g., ADD, ADHD, and dyslexia).

PMID- 14596567
TI  - Have we changed our view of the unconscious in contemporary clinical work? Panel
      report.

PMID- 14596568
TI  - Unconscious fantasy: its scientific status and clinical utility. Panel report.

PMID- 14596569
TI  - Analytic training and indirect countertransference.

PMID- 14596570
TI  - The role of specific consequences in the maintenance of three types of questions.
AB  - This research replicated and extended a study by Williams, Donley, and Keller
      (2000). In that study, children with autism received a box with an object inside
      and learned to ask "What's that?," "Can I see it?," and "Can I have it?" to have
      the name of the object, to see the object, and to get the object, respectively.
      The purpose of the present research was to determine if the three questions (a)
      were three independent repertoires of behavior, (b) constituted three instances
      of a single functional response class, or (c) belonged to a chain of behavior.
      The 3 boys with autism who participated responded independently to each question
      when the consequences for each question were altered. This indicates that the
      three target responses were three independent repertoires of behavior, each one
      reinforced and maintained with its specific consequences. Thus, this procedure
      serves to teach children with autism to ask questions with flexibility according
      to a variable context.

PMID- 14596571
TI  - The effects of presession attention on problem behavior maintained by different
      reinforcers.
AB  - The effect of presession attention on the later occurrence of problem behavior
      was examined with elementary-school children with a range of disabilities.
      Results of analogue functional analyses suggested an escape function, an
      attention function, or both. Following the analogue functional analyses, the
      effects of two antecedent conditions (10-min ignore vs. 10-min attention) were
      compared on problem behavior in subsequent test conditions. For participants who
      displayed attention-maintained problem behavior, the test condition involved
      contingent attention for problem behavior. For participants who displayed escape
      maintained problem behavior, the test condition involved contingent escape for
      problem behavior. Results indicated that participants who displayed attention
      maintained problem behavior displayed less problem behavior following presession
      exposure to attention than when ignored. No such effect was found for presession
      attention on escape-maintained problem behavior. We discuss matching antecedent
      based interventions to the results of functional analysis.

PMID- 14596572
TI  - On the relative contributions of positive reinforcement and escape extinction in
      the treatment of food refusal.
AB  - We compared the effects of positive reinforcement alone, escape extinction alone,
      and positive reinforcement with escape extinction in the treatment of the food
      and fluid refusal of 4 children who had been diagnosed with a pediatric feeding
      disorder. Consumption did not increase when positive reinforcement was
      implemented alone. By contrast, consumption increased for all participants when
      escape extinction was implemented, independent of the presence or absence of
      positive reinforcement. However, the addition of positive reinforcement to escape
      extinction was associated with beneficial effects (e.g., greater decreases in
      negative vocalizations and inappropriate behavior) for some participants.

PMID- 14596573
TI  - Behavioral treatment of children with phonological disorder: the efficacy of
      vocal imitation and sufficient-response-exemplar training.
AB  - This study examined whether sufficient-response-exemplar training of vocal
      imitation would result in improved articulation in children with phonological
      disorder, and whether improved articulation established in the context of vocal
      imitation would transfer to other verbal classes such as object naming and
      conversational speech. Participant 1 was 6 years old and attended first grade in
      a regular public school. Participant 2 was 5 years 4 months old and attended a
      public kindergarten. Both participants had normal hearing and no additional
      handicaps. A multiple baseline design across behaviors (target sounds or blends)
      was employed to examine whether the vocal imitation training resulted in improved
      articulation. Results showed that both participants improved articulation once
      training was implemented, and that the improved articulation transferred from
      vocal imitation to more natural speech such as object naming and conversational
      speech. Improvement established during training was maintained posttraining and
      at a 6-month follow-up.

PMID- 14596574
TI  - An analysis of aversive stimuli in classroom demand contexts.
AB  - Although recent research has identified numerous variables that can affect
      behavior maintained by negative reinforcement, questions remain concerning the
      potential aspects of the demand context that evoke problem behavior. To date, few
      studies have examined these questions within general education classrooms. The
      current study assessed the influence of social and task-difficulty variables on
      problem behavior maintained by negative reinforcement. Teachers in general
      education classrooms implemented three analyses to determine the influence of
      these variables on the problem behavior of 4 boys. Results are discussed in terms
      of response covariation within the demand context.

PMID- 14596575
TI  - The use of an escape contingency and a token economy to increase food acceptance.
AB  - Escape (termination of a meal) and token-based differential reinforcement of
      alternative behavior were used as reinforcement to increase acceptance of food.
      Using a changing criterion design, the number of bites accepted and consumed was
      gradually increased to 15 bites per meal. These data suggest that, in some cases,
      escape may be a potent reinforcer for food acceptance.

PMID- 14596576
TI  - Altering the timing of academic prompts to treat destructive behavior maintained
      by escape.
AB  - Following a functional analysis showing that destructive behavior was reinforced
      by escape, we altered the aversiveness of task demands by interspersing easy and
      difficult tasks and by presenting a corrective prompt as an antecedent event the
      next time a previously failed item was presented; this procedure was compared
      with one in which the corrective prompt was provided as an immediate consequence.
      Results of a reversal design showed that the antecedent prompt acted as an
      establishing operation and reduced destructive behavior to zero.

PMID- 14596577
TI  - Using simultaneous presentation to increase vegetable consumption in a mildly
      selective child with autism.
AB  - A multiple baseline design was used to evaluate the effects of adding condiments
      on the consumption of previously rejected foods (vegetables). Adding condiments
      produced increased food acceptance across three food items. Data are discussed in
      relation to conditioned food preferences and establishing operations.

PMID- 14596578
TI  - Training play behavior in a 5-year-old boy with developmental disabilities.
AB  - The purpose of the current study was twofold: (a) to investigate if it was
      possible to train three different games (both as a leader and as a participant)
      to a child with developmental disabilities through interaction with 4 typically
      developing peers, and (b) to examine if correct responding would be maintained
      after the training was faded. A multiple probe design across three games was
      used. The results showed that the child learned both skills as a leader and as a
      participant in all three games, and that skills were maintained for a period of 3
      weeks after the training had stopped.

PMID- 14596579
TI  - Self-control and the preference for delayed reinforcement an example in brain
      injury.
AB  - We investigated the effects of a concurrent physical therapy activity (keeping
      the hand open) during delays to reinforcement in an adult man with acquired brain
      injuries. Once a relatively stable level of hand-open behavior was obtained, the
      participant was asked to choose between a small immediate reinforcer and a larger
      delayed reinforcer contingent on keeping the hand open at greater-than-baseline
      duration. Afterwards, the participant was asked to select between a larger
      delayed reinforcer with no hand-open requirement and the identical larger delayed
      reinforcer with a progressively increasing hand-open requirement. Results suggest
      a shift in preference to larger delayed reinforcers and an eventual preference
      for the hand-open requirement option.

PMID- 14596580
TI  - Sequential evaluation of behavioral treatments and methylphenidate dosage for
      children with attention deficit hyperactivity disorder.
AB  - We used a sequential approach to evaluate the relative and combined effects of
      different types of behavioral treatments, as well as dosage of methylphenidate
      (MPH), on the disruptive behavior of 3 students who had been diagnosed with
      attention deficit hyperactivity disorder. Results showed that individualized
      behavioral treatments produced decreases in disruptive behavior equivalent to MPH
      for all 3 participants and demonstrated the need to evaluate behavioral
      treatments and medication dosage on an individual basis.

PMID- 14596581
TI  - The effects of differential negative reinforcement of other behavior and
      noncontingent escape on compliance.
AB  - The present study evaluated the effects of noncontingent escape and differential
      negative reinforcement of other behavior in reducing problem behaviors and
      increasing compliance in 2 children with disabilities. Results showed that both
      methods reduced problem behavior and increased compliance for both children.

PMID- 14596582
TI  - Parental assessment and treatment of food selectivity in natural settings.
AB  - This study evaluated the effects of a parent-conducted functional analysis and
      treatment consisting of differential reinforcement of an alternative behavior,
      escape extinction, and demand fading on food selectivity in a young child with
      autism. Increases in food acceptance at home and in a restaurant were obtained.

PMID- 14596583
TI  - Visual aids and structured criteria for improving visual inspection and
      interpretation of single-case designs.
AB  - Because behavior analysis is a data-driven process, a critical skill for behavior
      analysts is accurate visual inspection and interpretation of single-case data.
      Study 1 was a basic study in which we increased the accuracy of visual inspection
      methods for A-B designs through two refinements of the split-middle (SM) method
      called the dual-criteria (DC) and conservative dual-criteria (CDC) methods. The
      accuracy of these visual inspection methods was compared with one another and
      with two statistical methods (Allison & Gorman, 1993; Gottman, 1981) using a
      computer-simulated Monte Carlo study. Results indicated that the DC and CDC
      methods controlled Type I error rates much better than the SM method and had
      considerably higher power (to detect real treatment effects) than the two
      statistical methods. In Study 2, brief verbal and written instructions with
      modeling were used to train 5 staff members to use the DC method, and in Study 3,
      these training methods were incorporated into a slide presentation and were used
      to rapidly (i.e., 15 min) train a large group of individuals (N = 87).
      Interpretation accuracy increased from a baseline mean of 55% to a treatment mean
      of 94% in Study 2 and from a baseline mean of 71% to a treatment mean of 95% in
      Study 3. Thus, Study 1 answered basic questions about the accuracy of several
      methods of interpreting A-B designs; Study 2 showed how that information could be
      used to increase the accuracy of human visual inspectors; and Study 3 showed how
      the training procedures from Study 2 could be modified into a format that would
      facilitate rapid training of large groups of individuals to interpret single-case
      designs.

PMID- 14596584
TI  - Motivating operations and terms to describe them: some further refinements.
AB  - Over the past decade, behavior analysts have increasingly used the term
      establishing operation (EO) to refer to environmental events that influence the
      behavioral effects of operant consequences. Nonetheless, some elements of current
      terminology regarding EOs may interfere with applied behavior analysts' efforts
      to predict, control, describe, and understand behavior. The present paper (a)
      describes how the current conceptualization of the EO is in need of revision, (b)
      suggests alternative terms, including the generic term motivating operation (MO),
      and (c) provides examples of MOs and their behavioral effects using articles from
      the applied behavior analysis literature.

PMID- 14596586
TI  - Structure and function of malic enzymes, a new class of oxidative decarboxylases.
AB  - Malic enzyme is a tetrameric protein with double dimer structure in which the
      dimer interface is more intimately contacted than the tetramer interface. Each
      monomeric unit of the enzyme is composed of four structural domains, which show a
      different folding topology from those of the other oxidative decarboxylases. The
      active center is located at the interface between domains B and C. For human
      mitochondrial malic enzyme, there is an exo nucleotide-binding site for the
      inhibitor ATP and an allosteric site for the activator fumarate, located at the
      tetramer and dimer interfaces, respectively. Crystal structures of the enzyme in
      various complexed forms indicate that the enzyme may exist in equilibrium among
      two open and two closed forms. Interconversion among these forms involves rigid
      body movements of the four structural domains. Substrate binding at the active
      site shifts the open form to the closed form that represents an active site
      closure. Fumarate binding at the allosteric site induces the interconversion
      between forms I and II, which is mediated by the movements of domains A and D.
      Structures of malic enzyme from different sources are compared with an emphasis
      on the differences and their implications to structure-function relationships.
      The binding modes of the substrate, product, cofactors, and transition-state
      analogue at the active site, as well as ATP and fumarate at the exo site and
      allosteric site, respectively, provide a clear account for the catalytic
      mechanism, nucleotide specificities, allosteric regulation, and functional roles
      of the quaternary structure. The proposed catalytic mechanism involves tyrosine
      112 and lysine-183 as the general acid and base, respectively. In addition, a
      divalent metal ion (Mn(2+) or Mg(2+)) is essential in helping the catalysis.
      Binding of the metal ion also plays an important role in stabilizing the
      quaternary structural integrity of the enzyme.

PMID- 14596587
TI  - Melanopsin forms a functional short-wavelength photopigment.
AB  - Recently, melanopsin has emerged as the leading candidate for the elusive
      photopigment of the mammalian circadian system. This novel opsin-like protein is
      expressed in retinal ganglion cells that form the retinohypothalamic tract, a
      neuronal connection between the retina and the suprachiasmatic nucleus. These
      hypothalamic structures contain the circadian pacemaker, which generates daily
      rhythms in physiology and behavior. In mammals, proper synchronization of these
      rhythms to the environmental light-dark cycle requires retinal input.
      Surprisingly, rod and cone photoreceptors are not required. Instead, the
      melanopsin-containing ganglion cells are intrinsically sensitive to light,
      perhaps responding via a melanopsin-based signaling pathway. To test this
      hypothesis, we have characterized melanopsin following heterologous expression in
      COS cells. We found that melanopsin absorbed maximally at 424 nm after
      reconstitution with 11-cis-retinal. Furthermore, melanopsin activated the
      photoreceptor G-protein, transducin, in a light-dependent manner. In agreement
      with the measured absorbance spectrum, melanopsin was most efficiently excited by
      blue light (420-440 nm). In contrast, published action spectra suggest that the
      photopigment underlying the intrinsic light sensitivity of SCN-projecting RGCs
      has an absorption maximum near 484 nm. In summary, our experiments constitute the
      first direct demonstration that melanopsin forms a photopigment capable of
      activating a G-protein, but its spectral properties are not consistent with the
      action spectrum for circadian entrainment.

PMID- 14596588
TI  - Highly effective poly(ethylene glycol) architectures for specific inhibition of
      immune receptor activation.
AB  - Architectural features of synthetic ligands were systematically varied to
      optimize inhibition of mast cell degranulation initiated by multivalent crossing
      of IgE-receptor complexes. A series of ligands were generated by end-capping
      poly(ethylene glycol) (PEG) polymers and amine-based dendrimers with the hapten
      2,4-dinitrophenyl (DNP). These were used to explore the influence of polymeric
      backbone length, valency, and hapten presentation on binding to anti-DNP IgE and
      inhibition of stimulated activation of RBL cells. Monovalent MPEG(5000)-DNP
      (IC(50) = 50 nM), bivalent DNP-PEG(3350)-DNP (IC(50) = 8 nM), bismonovalent
      MPEG(5000)-DNP(2) (IC(50) = 20 nM), bisbivalent DNP(2)-PEG(3350)-DNP(2) (IC(50) =
      3nM) and DNP(4)-dendrimer ligands (IC(50) = 50 nM) all effectively inhibit
      cellular activation caused by multivalent antigen, DNP-bovine serum albumin. For
      different DNP ligands, we provide evidence for more effective inhibition due to
      (i) preferential formation of intra-IgE cross-links by bivalent ligands of
      sufficient length, (ii) self-association of monovalent ligands with longer tails,
      and (iii) higher probability of binding for bisvalent ligands. We also show that
      larger DNP(16)-dendrimers of higher valency trigger degranulation by cross
      linking IgE-receptor complexes, whereas smaller DNP-dendrimers are inhibitory.
      Thus, features of synthetic ligands can be manipulated to control receptor
      occupation, aggregation, and inhibition of the cellular response.

PMID- 14596589
TI  - Self-assembly of Abeta(1-42) into globular neurotoxins.
AB  - Amyloid beta 1-42 (Abeta(1-42)) is a self-associating peptide that becomes
      neurotoxic upon aggregation. Toxicity originally was attributed to the presence
      of large, readily formed Abeta fibrils, but a variety of other toxic species are
      now known. The current study shows that Abeta(1-42) can self-assemble into small,
      stable globular assemblies free of fibrils and protofibrils. Absence of large
      molecules was verified by atomic force microscopy (AFM) and nondenaturing gel
      electrophoresis. Denaturing electrophoresis revealed that the globular assemblies
      comprised oligomers ranging from trimers to 24mers. Oligomers prepared at 4
      degrees C stayed fibril-free for days and remained so when shifted to 37 degrees
      C, although the spectrum of sizes shifted toward larger oligomers at the higher
      temperature. The soluble, globular Abeta(1-42) oligomers were toxic to PC12
      cells, impairing reduction of MTT and interfering with ERK and Rac signal
      transduction. Occasionally, oligomers were neither toxic nor recognized by
      toxicity-neutralizing antibodies, suggesting that oligomers could assume
      alternative conformations. Tests for oligomerization-blocking activity were
      carried out by dot-blot immunoassays and showed that neuroprotective extracts of
      Ginkgo biloba could inhibit oligomer formation at very low doses. The observed
      neurotoxicity, structure, and stability of synthetic Abeta(1-42) globular
      assemblies support the hypothesis that Abeta(1-42) oligomers play a role in
      triggering nerve cell dysfunction and death in Alzheimer's disease.

PMID- 14596590
TI  - Jeltraxin, a frog egg jelly glycoprotein, has calcium-dependent lectin properties
      and is related to human serum pentraxins CRP and SAP.
AB  - The egg jelly that encapsulates amphibian eggs is essential for fertilization,
      but its molecular composition and roles remain largely unknown. We identified a
      calcium-dependent lectin from the pentraxin superfamily in the egg jelly coat
      from the South American burrowing frog, Lepidobatrachus laevis. This lectin,
      jeltraxin, was related to the host-response acute phase serum proteins C-reactive
      P component (CRP) and serum amyloid P component (SAP). The amino acid sequence of
      jeltraxin is 44% identical to that of Xenopus laevis CRP, 31-35% identical to
      those of mammalian CRP and SAP, and 21-27% identical to those of the large fusion
      pentraxins. Expression of jeltraxin mRNA was restricted to the oviduct, which
      distinguishes it as the first serum-related pentraxin not expressed in the liver.
      Purified jeltraxin was previously shown to exist in an oligomeric complex of
      approximately 250 kDa comprised of self-associating subunits. We have
      demonstrated by MALDI-TOF that this configuration is due to a decameric complex
      of 27.7 kDa subunits. Biotinylated jeltraxin bound to the high-molecular mass
      components of the egg jelly in a calcium-dependent manner with specificity for
      beta-galactose residues. On the basis of homology modeling, we predict that
      jeltraxin will coordinate two calcium ions. The function of jeltraxin will likely
      be related to its calcium-dependent lectin properties.

PMID- 14596591
TI  - Crystal structure of allo-Ile(A2)-insulin, an inactive chiral analogue:
      implications for the mechanism of receptor binding.
AB  - The crystal structure of an inactive chiral analogue of insulin containing
      nonstandard substitution allo-Ile(A2) is described at 2.0 A resolution. In native
      insulin, the invariant Ile(A2) side chain anchors the N-terminal alpha-helix of
      the A-chain to the hydrophobic core. The structure of the variant protein was
      determined by molecular replacement as a T(3)R(3) zinc hexamer. Whereas
      respective T- and R-state main-chain structures are similar to those of native
      insulin (main-chain root-mean-square deviations (RMSD) of 0.45 and 0.54 A,
      respectively), differences in core packing are observed near the variant side
      chain. The R-state core resembles that of the native R-state with a local
      inversion of A2 orientation (core side chain RMSD 0.75 A excluding A2); in the T
      state, allo-Ile(A2) exhibits an altered conformation in association with the
      reorganization of the surrounding side chains (RMSD 0.98 A). Surprisingly, the
      core of the R-state is similar to that observed in solution nuclear magnetic
      resonance (NMR) studies of an engineered T-like monomer containing the same
      chiral substitution (allo-Ile(A2)-DKP-insulin; Xu, B., Hua, Q. X., Nakagawa, S.
      H., Jia, W., Chu, Y. C., Katsoyannis, P. G., and Weiss, M. A. (2002) J. Mol.
      Biol. 316, 435-441). Simulation of NOESY spectra based on crystallographic
      protomers enables the analysis of similarities and differences in solution. The
      different responses of the T- and R-state cores to chiral perturbation
      illustrates both their intrinsic plasticity and constraints imposed by hexamer
      assembly. Although variant T- and R-protomers retain nativelike protein surfaces,
      the receptor-binding activity of allo-Ile(A2)-insulin is low (2% relative to
      native insulin). This seeming paradox suggests that insulin undergoes a change in
      conformation to expose Ile(A2) at the hormone-receptor interface.

PMID- 14596592
TI  - Structural elements required for deamidation of RhoA by cytotoxic necrotizing
      factor 1.
AB  - Cytotoxic necrotizing factor 1 (CNF1), a virulence factor expressed by pathogenic
      Escherichia coli, acts on Rho-GTPases and specifically deamidates a single
      glutamine residue (Gln-63 in RhoA) required for GTP hydrolysis. This modification
      constitutively activates the effector binding function of Rho-GTPases and
      eventually leads to their proteasome-mediated degradation. Previous structural
      investigation revealed that the CNF1 active site is located in a deep and narrow
      pocket and that the entrance to this pocket is formed by nine loop segments. We
      have examined the functional importance of five of these loops (2, 6, 7, 8, and
      9) by deleting them individually. We find that deletion of proximally located
      loops 8 and 9 in the 32 kDa catalytic domain of CNF1 (CNF1-C) nearly or
      completely abolishes deamidation of RhoA in vitro, identifying a potential Rho
      GTPase recognition site. Deletion of loop 7 causes protein folding errors, and
      deletion of loop 6 has a small effect on deamidation. In contrast, deletion of
      loop 2 is found to increase deamidation 5-7-fold, implying that this loop
      rearranges in binding RhoA. None of the loop deletions or wild-type CNF1-C is
      able to deamidate RhoA containing Asn-63 instead of Gln-63, suggesting that the
      fit between the toxin and its target is highly precise. In addition, we show that
      the specificity constant (k(cat)/K(m)) of CNF1-C for RhoA is 825 +/- 3 M(-1) s(
      1). This modest value is consistent with the confining size of the active site
      pocket acting to exclude nonspecific targets but also limiting reactivity toward
      intended targets.

PMID- 14596593
TI  - Cellular effects of small molecule PTP1B inhibitors on insulin signaling.
AB  - Protein tyrosine phosphatase 1B (PTP1B) is implicated as a negative regulator of
      insulin receptor (IR) signaling and a potential drug target for the treatment of
      type 2 diabetes and other associated metabolic syndromes. To further define the
      role of PTP1B in insulin signaling and to test the hypothesis that blocking the
      activity of PTP1B would augment the action of insulin, we prepared several cell
      permeable, potent and selective, small molecule PTP1B inhibitors, and evaluated
      their biological effects in several insulin sensitive cell lines. Our data
      indicate that PTP1B inhibitors bind to and colocalize with PTP1B on the surface
      of the endoplasmic reticulum and PTP1B exerts its negative effect on insulin
      signaling upstream of phosphatidylinositol 3-kinase and MEK1. Treatment of cells
      with PTP1B inhibitors, both in the presence and in the absence of insulin,
      markedly enhances IRbeta and IRS-1 phosphorylation, Akt and ERK1/2 activation,
      Glut4 translocation, glucose uptake, and Elk1 transcriptional activation and cell
      proliferation. These results indicate that small molecule inhibitors targeted to
      PTP1B can act as both insulin mimetics and insulin sensitizers. Taken together,
      our findings combined with results from PTP1B knockout, antisense, and
      biochemical studies provide strong evidence that PTP1B negatively regulates
      insulin signaling and that small molecule PTP1B inhibitors have the ability to
      potentiate and augment the action of insulin.

PMID- 14596595
TI  - Novel destabilization of nucleotide binding by the gamma phosphate of ATP in the
      yeast SR protein kinase Sky1p.
AB  - SR protein kinases (SRPKs) regulate the temporal and cell-specific selection of
      alternative splice sites. These enzymes are highly unique members of the protein
      kinase family. SRPKs contain a large domain insert (approximately 200 residues)
      within the kinase core, do not require phosphorylation for regulation, have an
      extended helix insert near the nucleotide pocket, and possess unusual substrate
      specificity determinants. The yeast SRPK, Sky1p, rapidly phosphorylates its
      natural substrate Npl3 but binds ATP with a high K(m), suggesting that some of
      these distinctive structural features may be correlated with nucleotide binding
      [Aubol et al. (2002) Biochemistry 41, 10002-10009]. To address this issue, the
      nucleotide binding properties of Sky1p were studied using fluorescence
      spectroscopy. The affinities of several nucleotides (ATP, ADP, AMP, adenosine,
      and AMPPNP) to Sky1p and the prototype kinase, cAMP-dependent protein kinase,
      were compared in the absence and presence of the metal activator, Mg(2+), using a
      fluorescence-based displacement assay. The data indicate that Sky1p, unlike cAMP
      dependent protein kinase, potently destabilizes the gamma phosphate of ATP. This
      novel finding suggests that rapid phosphoryl transfer may be facilitated by
      unique mechanisms in both protein kinases.

PMID- 14596594
TI  - Lecithin retinol acyltransferase is a founder member of a novel family of
      enzymes.
AB  - Lecithin retinol acyltransferase (LRAT) catalyzes the reversible esterification
      of vitamin A using lecithin as the acyl donor. LRAT is the founder member of a
      new class of enzymes, which include class II tumor suppressors, proteins
      essential for development, and putative proteases. All of these proteins possess
      Cys and His residues homologous to C161 and H60 of LRAT. These two residues are
      shown here to be essential for LRAT activity and are part of a catalytic dyad
      reminiscent of that found in thiol proteases. However, the local primary sequence
      contexts of C161 and H60 of LRAT and family are not at all homologous to those
      found in the approximately 20 thiol protease families. Moreover, LRAT shows pKs
      of 8.3 and 10.8, compared to approximately 4.0 and 8.5 observed in the thiol
      proteases. LRAT also contains Gln177 and Asp67 residues, which are largely
      conserved in the homologues. However, neither of these residues is essential for
      catalysis. Thiol proteases often contain catalytically essential Asp or Gln
      residues. It is concluded that LRAT is the founder member of a new class of Cys
      His enzymes with diverse functions.

PMID- 14596596
TI  - A complex of chaperones and disulfide isomerases occludes the cytosolic face of
      the translocation protein Sec61p and affects translocation of the prion protein.
AB  - Secretion of newly synthesized proteins across the mammalian rough endoplasmic
      reticulum (translocation) is supported by the membrane proteins Sec61p and TRAM,
      but may also include accessory factors, depending on the particular translocation
      substrate. Studies designed to investigate the binding of anti-peptide antibodies
      to the carboxyl terminus of the alpha-subunit of Sec61 (Sec61palpha) lead us to
      the isolation of a complex of proteins that occlude the cytosolic face of
      Sec61palpha in microsomes that have been prepared by standard protocols used to
      study translocation in vitro [Walter, P., and Blobel, G. (1983) Methods Enzymol.
      96, 84-93]. This complex was shown by nanospray tandem mass spectrometry to be
      composed of protein disulfide isomerase (PDI), calcium binding protein 1
      (CABP1/P5), 72 kDa endoplasmic reticulum protein (ERp72), and BiP (heat shock
      protein A5/HSPA5), and has been named TR-PDI for "translocon-resident protein
      disulfide isomerase complex". This constitutes a novel location for these
      proteins, which are known to be major constituents of the lumen of the rough
      endoplasmic reticulum. We have not established the function of TR-PDI at this
      location, but did observe that the absence of this complex results in a relative
      loss of correct topology of prion protein insertion across RER membranes,
      indicating the possibility of a functional role in vivo.

PMID- 14596597
TI  - Crystal structure of the sensor domain of the BlaR penicillin receptor from
      Bacillus licheniformis.
AB  - As in several staphylococci, the synthesis of the Bacillus licheniformis 749/I
      beta-lactamase is an inducible phenomenon regulated by a signal-transducing
      membrane protein BlaR. The C-terminal domain of this multimodular protein is an
      extracellular domain which specifically recognizes beta-lactam antibiotics. When
      it binds a beta-lactam, a signal is transmitted by the transmembrane region to
      the intracellular loops. In response, the hydrolytic activity of the BlaR large
      cytoplasmic L3 loop is induced, and a cascade of reactions is generated, leading
      to the transcription of the beta-lactamase gene. Here, we describe the crystal
      structure of the extracellular penicillin-receptor domain of BlaR (residues 346
      601) at 2.5 A resolution in order to understand why this domain, whose folding is
      very similar to that of class D beta-lactamases, behaves as a highly sensitive
      penicillin-binding protein rather than a beta-lactamase. Two residues of the BlaR
      C-terminal domain, Thr452 and Thr542, modify the hydrophobic characteristic of
      the class D beta-lactamase active site. Both residues seem to be in part
      responsible for the lack of beta-lactamase activity of the BlaR protein due to
      the stability of the acyl-enzyme. Although further experimental data are needed
      to fully understand the transmembrane induction process, the comparison of the
      BlaR sensor domain structure with those of class D beta-lactamase complexes and
      penicillin-binding proteins provides interesting elements to hypothesize on
      possible signal transmission mechanisms.

PMID- 14596598
TI  - Catalytic implications from the Drosophila protein L-isoaspartyl
      methyltransferase structure and site-directed mutagenesis.
AB  - Protein L-isoaspartyl methyltransferases (PIMT; EC 2.1.1.77) catalyze the S
      adenosylmethionine-dependent methylation of L-isoaspartyl residues that arise
      spontaneously in proteins with age, thereby initiating a repair process that
      restores the normal backbone configuration to the damaged polypeptide. In
      Drosophila melanogaster, overexpression of PIMT in transgenic flies extends the
      normal life span, suggesting that protein damage can be a limiting factor in
      longevity. To understand structural features of the Drosophila PIMT (dPIMT)
      important for catalysis, the crystal structure of dPIMT was determined at a
      resolution of 2.2 A, and site-directed mutagenesis was used to identify the role
      of Ser-60 in catalysis. The core structure of dPIMT is similar to the modified
      nucleotide-binding fold observed in PIMTs from extreme thermophiles and humans. A
      striking difference of the dPIMT structure is the rotation of the C-terminal
      residues by 90 degrees relative to the homologous structures. Effectively, this
      displacement generates a more open conformation that allows greater solvent
      access to S-adenosylhomocysteine, which is almost completely buried in other PIMT
      structures. The enzyme may alternate between the open conformation found for
      dPIMT and the more closed conformations described for other PIMTs during its
      catalytic cycle, thereby allowing the exchange of substrates and products.
      Catalysis by dPIMT requires the side chain of the conserved, active site residue
      Ser-60, since substitution of this residue with Thr, Gln, or Ala reduces or
      abolishes the methylation of both protein and isoaspartyl peptide substrates.

PMID- 14596599
TI  - Crystal structure of serine dehydratase from rat liver.
AB  - SDH (L-serine dehydratase, EC 4.3.1.17) catalyzes the pyridoxal 5'-phosphate
      (PLP)-dependent dehydration of L-serine to yield pyruvate and ammonia. Liver SDH
      plays an important role in gluconeogenesis. Formation of pyruvate by SDH is a two
      step reaction in which the hydroxyl group of serine is cleaved to produce
      aminoacrylate, and then the aminoacrylate is deaminated by nonenzymatic
      hydrolysis to produce pyruvate. The crystal structure of rat liver apo-SDH was
      determined by single isomorphous replacement at 2.8 A resolution. The holo-SDH
      crystallized with O-methylserine (OMS) was also determined at 2.6 A resolution by
      molecular replacement. SDH is composed of two domains, and each domain has a
      typical alphabeta-open structure. The active site is located in the cleft between
      the two domains. The holo-SDH contained PLP-OMS aldimine in the active site,
      indicating that OMS can form the Schiff base linkage with PLP, but the subsequent
      dehydration did not occur. Apo-SDH forms a dimer by inserting the small domain
      into the catalytic cleft of the partner subunit so that the active site is
      closed. Holo-SDH also forms a dimer by making contacts at the back of the clefts
      so that the dimerization does not close the catalytic cleft. The phosphate group
      of PLP is surrounded by a characteristic G-rich sequence ((168)GGGGL(172)) and
      forms hydrogen bonds with the amide groups of those amino acid residues,
      suggesting that the phosphate group can be protonated. N(1) of PLP participates
      in a hydrogen bond with Cys303, and similar hydrogen bonds with N(1)
      participating are seen in other beta-elimination enzymes. These hydrogen bonding
      schemes indicate that N(1) is not protonated, and thus, the pyridine ring cannot
      take a quinone-like structure. These characteristics of the bound PLP suggest
      that SDH catalysis is not facilitated by forming the resonance-stabilized
      structure of the PLP-Ser aldimine as seen in aminotransferases. A possible
      catalytic mechanism involves the phosphate group, surrounded by the
      characteristic sequence, acting as a general acid to donate a proton to the
      leaving hydroxyl group of serine.

PMID- 14596600
TI  - Analysis of membrane-binding properties of dermaseptin analogues: relationships
      between binding and cytotoxicity.
AB  - To understand relationships between membrane-binding properties of cytolytic
      peptides and resulting cytotoxicity, we investigated interactions of dermaseptin
      analogues with model bilayers by means of surface plasmon resonance. First, we
      tested the system by comparing two native dermaseptins, S1 and S4, whose binding
      properties were previously characterized in different experimental systems.
      Validation experiments revealed deviations from the one-to-one interaction model
      and indicated the binding to proceed by a two-stage mechanism. By calculation of
      apparent affinity constants and individual affinities for both steps of the
      interaction, the biosensor technology was able to distinguish between surface
      bound peptides that subsequently penetrated into the bilayer and peptides that
      remained essentially superficially bound. This data interpretation was sustained
      after analysis of a series of dermaseptin S4 derivatives whose binding data were
      compared with cytotoxicity, revealing cytolytic activity to correlate mainly with
      insertion affinity. The data indicate that the potency of highly cytolytic
      peptides such as K(4)K(20)-S4 is not due to the highest membrane adhesion
      affinity but to the highest propensity for the inserted state. Similarly,
      truncated derivatives of 16, 13, and 10 residues showed a progressive reduction
      in cytotoxicity that best correlated with progressive reduction in insertion
      affinity. Support for the adhesion versus inserted states was provided by
      proteolytic experiments with RBC-bound peptides that demonstrated K(4)K(20)-S4 to
      be protected from enzymatic cleavage, unlike its 13-mer derivative. Overall,
      using the two-stage model proved instrumental in investigating membrane-binding
      properties of antimicrobial peptides and capable of explaining the cytolytic
      properties of closely related analogues.

PMID- 14596601
TI  - Analysis of catalytic carboxylate mutants E552Q and E1197Q suggests asymmetric
      ATP hydrolysis by the two nucleotide-binding domains of P-glycoprotein.
AB  - In the nucleotide-binding domains (NBDs) of ABC transporters, such as mouse Mdr3
      P-glycoprotein (P-gp), an invariant carboxylate residue (E552 in NBD1; E1197 in
      NBD2) immediately follows the Walker B motif (hyd(4)DE/D). Removal of the
      negative charge in mutants E552Q and E1197Q abolishes drug-stimulated ATPase
      activity measured by P(i) release. Surprisingly, drug-stimulated trapping of 8
      azido-[alpha-(32)P]ATP is still observed in the mutants in both the presence and
      absence of the transition-state analogue vanadate (V(i)), and ADP can be
      recovered from the trapped enzymes. The E552Q and E1197Q mutants show
      characteristics similar to those of the wild-type (WT) enzyme with respect to 8
      azido-[alpha-(32)P]ATP binding and 8-azido-[alpha-(32)P]nucleotide trapping, with
      the latter being both Mg(2+) and temperature dependent. Importantly, drug
      stimulated nucleotide trapping in E552Q is stimulated by V(i) and resembles the
      WT enzyme, while it is almost completely V(i) insensitive in E1197Q. Similar
      nucleotide trapping properties are observed when aluminum fluoride or beryllium
      fluoride is used as an alternate transition-state analogue. Partial proteolytic
      cleavage of photolabeled enzymes indicates that, in the absence of V(i),
      nucleotide trapping occurs exclusively at the mutant NBD, whereas in the presence
      of V(i), nucleotide trapping occurs at both NBDs. Together, these results suggest
      that there is single-site turnover occurring in the E552Q and E1197Q mutants and
      that ADP release from the mutant site, or another catalytic step, is impaired in
      these mutants. Furthermore, our results support a model in which the two NBDs of
      P-gp are not functionally equivalent.

PMID- 14596603
TI  - A transient intermediate in the reaction catalyzed by (S)-mandelate dehydrogenase
      from Pseudomonas putida.
AB  - (S)-Mandelate dehydrogenase from Pseudomonas putida is a member of a FMN
      dependent enzyme family that oxidizes (S)-alpha-hydroxyacids to alpha-ketoacids.
      The reductive half-reaction consists of the steps involved in substrate oxidation
      and FMN reduction. In this study, we investigated the mechanism of this half
      reaction in detail. At low temperatures, a transient intermediate was formed in
      the course of the FMN reduction reaction. This intermediate is characteristic of
      a charge-transfer complex of oxidized FMN and an electron-rich donor and is
      formed prior to full reduction of the flavin. The intermediate was not due to
      binding of anionic substrates or inhibitors. It was only observed with efficient
      substrates that have high k(cat) values. At higher temperatures, it was formed
      within the dead time of the stopped-flow instrument. The rate of formation of the
      intermediate was 3-4-fold faster than its rate of disappearance; the former had a
      larger isotope effect. This suggests that the charge-transfer donor is an
      electron-rich carbanion/enolate intermediate that is generated by the base
      catalyzed abstraction of the substrate alpha-proton. This is consistent with the
      observation that the intermediate was not observed with the R277K and R277G
      mutants, which have been shown to destabilize the carbanion intermediate (Lehoux,
      I. E., and Mitra, B. (2000) Biochemistry 39, 10055-10065). Thus, the MDH reaction
      has two rate-limiting steps of similar activation energies: the formation and
      breakdown of a distinct intermediate, with the latter step being slightly more
      rate limiting. We also show that MDH is capable of catalyzing the reverse
      reaction, the reoxidation of reduced MDH by the product ketoacid, benzoylformate.
      The transient intermediate was observed during the reverse reaction as well,
      confirming that it is indeed a true intermediate in the MDH reaction pathway.

PMID- 14596602
TI  - Does the S2 rod of myosin II uncoil upon two-headed binding to actin? A leucine
      zippered HMM study.
AB  - Myosin II, like many molecular motors, is a two-headed dimer held together by a
      coiled-coil rod. The stability of the (S2) rod has implications for head-head
      interactions, force generation, and possibly regulation. Whether S2 uncoils has
      been controversial. To test the stability of S2, we constructed a series of
      "zippered" dimeric smooth muscle myosin II compounds, containing a high-melting
      temperature 32-amino acid GCN4 leucine zipper in the S2 rod beginning 0, 1, 2, or
      15 heptads from the head-rod junction. We then assessed the ability of these and
      wild-type myosin to bind strongly via two heads to an actin filament by measuring
      the fluorescence quenching of pyrene-labeled actin induced by myosin binding.
      Such two-headed binding is expected to exert a large strain that tends to uncoil
      S2, and hence provide a robust test of S2 stability. We find that wild-type and
      zippered heavy meromyosin (HMM) are able to bind by both heads to actin under
      both nucleotide-free and saturating ADP conditions. In addition, we compared the
      actin affinity and rates for the 0- and 15-zippered HMMs in the phosphorylated
      "on" state and found them to be very similar. These results strongly suggest that
      S2 uncoiling is not necessary for two-headed binding of myosin to actin,
      presumably due to a compliant point in the myosin head(s). We conclude that S2
      likely remains intact during the catalytic cycle.

PMID- 14596604
TI  - Pre-steady-state analysis of the nucleoside hydrolase of Trypanosoma vivax.
      Evidence for half-of-the-sites reactivity and rate-limiting product release.
AB  - The nucleoside hydrolase (NH) of the Trypanosoma vivax parasite catalyzes the
      hydrolysis of the N-glycosidic bond in ribonucleosides according to the following
      reaction: beta-purine (or pyrimidine) nucleoside + H(2)O --> purine (pyrimidine)
      base + ribose. The reaction follows a highly dissociative nucleophilic
      displacement reaction mechanism with a ribosyl oxocarbenium-like transition
      state. This paper describes the first pre-steady-state analysis of the conversion
      of a number of purine nucleosides. The NH exhibits burst kinetics and behaves
      with half-of-the-sites reactivity. The analysis suggests that the NH of T. vivax
      follows a complex multistep mechanism in which a common slow step different from
      the chemical hydrolysis is rate limiting. Stopped-flow fluorescence binding
      experiments with ribose indicate that a tightly bound enzyme-ribose complex
      accumulates during the enzymatic hydrolysis of the common purine nucleosides.
      This is caused by a slow isomerization between a tight and a loose enzyme-ribose
      complex forming the rate-limiting step on the reaction coordinate.

PMID- 14596605
TI  - Replication protein A interactions with DNA: differential binding of the core
      domains and analysis of the DNA interaction surface.
AB  - Human replication protein A (RPA) is a heterotrimeric (70, 32, and 14 kDa
      subunits), eukaryotic single-stranded DNA (ssDNA) binding protein required for
      DNA recombination, repair, and replication. The three subunits of human RPA are
      composed of six conserved DNA binding domains (DBDs). Deletion and mutational
      studies have identified a high-affinity DNA binding core in the central region of
      the 70 kDa subunit, composed of DBDs A and B. To define the roles of each DBD in
      DNA binding, monomeric and tandem DBD A and B domain chimeras were created and
      characterized. Individually, DBDs A and B have a very low intrinsic affinity for
      ssDNA. In contrast, tandem DBDs (AA, AB, BA, and BB) bind ssDNA with moderate to
      high affinity. The AA chimera had a much higher affinity for ssDNA than did the
      other tandem DBDs, demonstrating that DBD A has a higher intrinsic affinity for
      ssDNA than DBD B. The RPA-DNA interface is similar in both DBD A and DBD B.
      Mutational analysis was carried out to probe the relative contributions of the
      two domains to DNA binding. Mutation of polar residues in either core DBD
      resulted in a significant decrease in the affinity of the RPA complex for ssDNA.
      RPA complexes with pairs of mutated polar residues had lower affinities than
      those with single mutations. The decrease in affinity observed when polar
      mutations were combined suggests that multiple polar interactions contribute to
      the affinity of the RPA core for DNA. These results indicate that RPA-ssDNA
      interactions are the result of binding of multiple nonequivalent domains. Our
      data are consistent with a sequential binding model for RPA, in which DBD A is
      responsible for positioning and initial binding of the RPA complex while DBD A
      together with DBD B direct stable, high-affinity binding to ssDNA.

PMID- 14596606
TI  - Alpha-synuclein association with phosphatidylglycerol probed by lipid spin
      labels.
AB  - Alpha-synuclein is a small presynaptic protein, which is linked to the
      development of Parkinson's disease. Alpha-synuclein partitions between cytosolic
      and vesicle-bound states, where membrane binding is accompanied by the formation
      of an amphipathic helix in the N-terminal section of the otherwise unstructured
      protein. The impact on alpha-synuclein of binding to vesicle-like liposomes has
      been studied extensively, but far less is known about the impact of alpha
      synuclein on the membrane. The interactions of alpha-synuclein with
      phosphatidylglycerol membranes are studied here by using spin-labeled lipid
      species and electron spin resonance (ESR) spectroscopy to allow a detailed
      analysis of the effect on the membrane lipids. Membrane association of alpha
      synuclein perturbs the ESR spectra of spin-labeled lipids in bilayers of
      phosphatidylglycerol but not of phosphatidylcholine. The interaction is inhibited
      at high ionic strength. The segmental motion is hindered at all positions of spin
      labeling in the phosphatidylglycerol sn-2 chain, while still preserving the chain
      flexibility gradient characteristic of fluid phospholipid membranes. Direct
      motional restriction of the lipid chains, resulting from penetration of the
      protein into the hydrophobic interior of the membrane, is not observed.
      Saturation occurs at a protein/lipid ratio corresponding to approximately 36
      lipids/protein added. Alpha-synuclein exhibits a selectivity of interaction with
      different phospholipid spin labels when bound to phosphatidylglycerol membranes
      in the following order: stearic acid > cardiolipin > phosphatidylcholine >
      phosphatidylglycerol approximately phosphatidylethanolamine > phosphatidic acid
      approximately phosphatidylserine > N-acyl phosphatidylethanolamine > diglyceride.
      Accordingly, membrane-bound alpha-synuclein associates at the interfacial region
      of the bilayer where it may favor a local concentration of certain phospholipids.

PMID- 14596607
TI  - Histidine-834 of human erythrocyte band 3 has an essential role in the
      conformational changes that occur during the band 3-mediated anion exchange.
AB  - We have shown that diethyl pyrocarbonate (DEPC) inhibits band 3-mediated anion
      exchange and that the inhibition occurs only when histidine residue(s) is (are)
      modified with DEPC from the cytosolic surface of resealed ghosts [Izuhara et al.
      (1989) Biochemistry 28, 4725-4728]. In the present study, we have identified the
      DEPC-modified histidine residue as His834 using liquid chromatography with
      electrospray ionization mass spectrometry (LC/ESI-MS). This mild, rapid,
      sensitive, and quantitative method was successfully applied to analysis of the
      unstable DEPC-histidine adduct. The DEPC modification of His834 was pH dependent
      and 4,4'-dinitrostilbene-2,2'-disulfonic acid (DNDS) sensitive as previously
      shown. After DEPC modification, band 3-mediated anion exchange is inhibited.
      Consistent with previous results, we confirmed that His834 was located on the
      cytosolic side of the membrane and the DEPC modification of His834 had allosteric
      effects on the extracellular DNDS-binding site of band 3. Therefore, we conclude
      that His834 is located at the cytosolic surface of band 3 and is an essential
      residue for band 3-mediated anion exchange. We will discuss important roles of
      the region from TM12 to TM14 in the conformational changes that occur during the
      band 3-mediated anion exchange.

PMID- 14596608
TI  - Synthesis and characterization of delta-atracotoxin-Ar1a, the lethal neurotoxin
      from venom of the Sydney funnel-web spider (Atrax robustus).
AB  - Delta-atracotoxin-Ar1a (delta-ACTX-Ar1a) is the major polypeptide neurotoxin
      isolated from the venom of the male Sydney funnel-web spider, Atrax robustus.
      This neurotoxin targets both insect and mammalian voltage-gated sodium channels,
      where it competes with scorpion alpha-toxins for neurotoxin receptor site-3 to
      slow sodium-channel inactivation. Progress in characterizing the structure and
      mechanism of action of this toxin has been hampered by the limited supply of pure
      toxin from natural sources. In this paper, we describe the first successful
      chemical synthesis and oxidative refolding of the four-disulfide bond containing
      delta-ACTX-Ar1a. This synthesis involved solid-phase Boc chemistry using double
      coupling, followed by oxidative folding of purified peptide using a buffer of 2 M
      GdnHCl and glutathione/glutathiol in a 1:1 mixture of 2-propanol (pH 8.5).
      Successful oxidation and refolding was confirmed using both chemical and
      pharmacological characterization. Ion spray mass spectrometry was employed to
      confirm the molecular weight. (1)H NMR analysis showed identical chemical shifts
      for native and synthetic toxins, indicating that the synthetic toxin adopts the
      native fold. Pharmacological studies employing whole-cell patch clamp recordings
      from rat dorsal root ganglion neurons confirmed that synthetic delta-ACTX-Ar1a
      produced a slowing of the sodium current inactivation and hyperpolarizing shifts
      in the voltage-dependence of activation and inactivation similar to native toxin.
      Under current clamp conditions, we show for the first time that delta-ACTX-Ar1a
      produces spontaneous repetitive plateau potentials underlying the clinical
      symptoms seen during envenomation. This successful oxidative refolding of
      synthetic delta-ACTX-Ar1a paves the way for future structure-activity studies to
      determine the toxin pharmacophore.

PMID- 14596609
TI  - Interactions between charged amino acid residues within transmembrane helices in
      the sulfate transporter SHST1.
AB  - The aim of this study was to identify charged amino acid residues important for
      activity of the sulfate transporter SHST1. We mutated 10 charged amino acids in
      or near proposed transmembrane helices and expressed the resulting mutants in a
      sulfate transport-deficient yeast strain. Mutations affecting four residues
      resulted in a complete loss of sulfate transport; these residues were D107 and
      D122 in helix 1 and R354 and E366 in helix 8. All other mutants showed some
      reduction in transport activity. The E366Q mutant was unusual in that expression
      of the mutant protein was toxic to yeast cells. The R354Q mutant showed reduced
      trafficking to the plasma membrane, indicating that the protein was misfolded.
      However, transporter function (to a low level) and wild-type trafficking could be
      recovered by combining the R354Q mutation with either the E175Q or E270Q
      mutations. This suggested that R354 interacts with both E175 and E270. The triple
      mutant E175Q/E270Q/R354Q retained only marginal sulfate transport activity but
      was trafficked at wild-type levels, suggesting that a charge network between
      these three residues may be involved in the transport pathway, rather than in
      folding. D107 was also found to be essential for the ion transport pathway and
      may form a charge pair with R154, both of which are highly conserved. The
      information obtained on interactions between charged residues provides the first
      evidence for the possible spatial arrangement of transmembrane helices within any
      member of this transporter family. This information is used to develop a model
      for SHST1 tertiary structure.

PMID- 14596610
TI  - Mass spectrometric based mapping of the disulfide bonding patterns of integrin
      alpha chains.
AB  - Integrins are one of the major mediators of cellular adherence. Structurally the
      component alpha and beta chains are characterized by extensive intrachain
      disulfide bonding. The assignment of these bonds is currently based on homology
      with the chains of the integrin alphaIIbbeta3. However, recent crystallographic
      analysis of the soluble alphaVbeta3 construct indicates that the alphaV chain
      displays bonding patterns different from those predicted for alphaIIb. In an
      effort to define the disulfide bonding patterns in integrins, we have used mass
      spectrometric based approaches to map the human alpha3, alpha5, alphaV, and
      alphaIIb. The results indicate that there are differences in the disulfide
      patterns of the alpha chains. These do not correlate with the integrin capacity
      to bind ligands as all integrins used in the present study displayed functional
      activity. The differences were observed in the bonding patterns linking the heavy
      (H) and light (L) components of the of the alpha chains. It was also possible to
      assign the location in alpha5 of an additional disulfide bond involving a pair of
      cysteines not present in alphaV or alphaIIb. This second bond between the H and L
      chains of alpha5 has not been previously described. These results indicate that
      not all integrin species display the same disulfide bonding patterns. They also
      highlight the need for caution in the use of assignments based on sequence
      homology.

PMID- 14596611
TI  - Monomers and oligomers of the M2 muscarinic cholinergic receptor purified from
      Sf9 cells.
AB  - G protein-coupled receptors are known to form oligomers. To probe the nature of
      such aggregates, as well as the role and prevalence of monomers, epitope-tagged
      forms of the M(2) muscarinic receptor have been isolated as oligomers and
      monomers from Sf9 cells. Membranes from cells coexpressing the c-Myc- and FLAG
      tagged receptor were solubilized in digitonin-cholate, and the receptor was
      purified by successive passage through DEAE-Sepharose, the affinity resin 3-(2'
      aminobenzhydryloxy)tropane (ABT)-Sepharose, and hydroxyapatite.
      Coimmunoprecipitation of the two epitopes indicated the presence of oligomers at
      each stage of the purification up to but not including the fraction eluted
      specifically from ABT-Sepharose. The affinity-purified receptor therefore
      appeared to be monomeric. The failure to detect coimmunoprecipitation was not due
      to an ineffective antibody, nor did the conditions of purification appear to
      promote disaggregation. Receptor at all stages of purification bound N
      [(3)H]methylscopolamine and [(3)H]quinuclidinylbenzilate with high affinity, but
      the capacity of receptors that were not retained on ABT-Sepharose was only 4% of
      that expected from densitometry of western blots probed with an anti-M(2)
      antibody. Similarly low activity was found with oligomers isolated by successive
      passage of coexpressed receptor on anti-c-Myc and anti-FLAG immunoaffinity
      columns. M(2) muscarinic receptors therefore appear to coexist as active monomers
      and largely or wholly inactive oligomers in solubilized extracts of Sf9 cells. A
      different pattern emerged when coinfected cells were treated with
      quinuclidinylbenzilate prior to solubilization, in that ABT-purified receptors
      from those cells exhibited coimmunoprecipitation. Treatment with the antagonist
      therefore led to oligomers in which at least some of the constituent sites were
      active and were retained by ABT-Sepharose.

PMID- 14596612
TI  - Interaction of neuropeptide Y and Hsp90 through a novel peptide binding region.
AB  - Hsp90 is a molecular chaperone that binds and assists refolding of non-native
      and/or labile polypeptides and also bind various peptides. However, the rules of
      how Hsp90 recognizes substrates have not been well characterized. By surface
      plasmon resonance measurements, a physiologically active peptide, neuropeptide Y
      (NPY), with a strong binding property to Hsp90 was identified from screening of
      38 randomly selected peptide candidates. We showed that the carboxy-terminal
      fragment of NPY (NPY13-36), which forms an amphipathic alpha-helix structure,
      preserved the strong binding to Hsp90. Immunoprecipitation and immunoblotting
      using HeLa cell extracts revealed that newly synthesized NPY precursors bound to
      Hsp90, suggesting that the in vitro binding experiments identified an interactive
      peptide in vivo. Proteolytic cleavage of the NPY13-36/Hsp90 complex, as well as
      binding site analysis using deletion mutants of Hsp90, revealed the NPY binding
      locus on Hsp90alpha as the 192 amino acid region following the N-terminal domain.
      By electron microscopic analysis using an anti-Hsp90 antibody against the
      sequence proximal to the highly charged region, we showed that the Hsp90 dimer
      bound to NPY13-36 at both ends. Mutation of arginine residues in NPY13-36 to
      alanine abrogated binding to Hsp90. Our studies indicate that the hinge region
      after the N-terminal domain of Hsp90 and the positive charges on NPY are
      important for this interaction.

PMID- 14596613
TI  - Trimeric subunit stoichiometry of the glutamate transporters from Bacillus
      caldotenax and Bacillus stearothermophilus.
AB  - Catalysis of glutamate transport across cell membranes and coupling of the
      concentrative transport to sodium, proton, and potassium gradients are processes
      fundamental to organisms in all kingdoms of life. In bacteria, glutamate
      transporters participate in nutrient uptake, while in eukaryotic organisms, the
      transporters clear glutamate from the synaptic cleft. Even though glutamate
      transporters are crucial to the viability of many life forms, little is known
      about their structure and quaternary organization. In particular, the subunit
      stoichiometry of these polytopic integral membrane proteins has not been
      unequivocally defined. Determination of the native molecular mass of membrane
      proteins is complicated by their lability in detergent micelles and by their
      association with detergent and/or lipid molecules. Here we report the
      purification of glutamate transporters from Bacillus caldotenax and Bacillus
      stearothermophilus in a monodisperse, detergent-solubilized state.
      Characterization of both transporters either by chemical cross-linking and mass
      spectrometry or by size-exclusion chromatography and in-line laser light
      scattering, refractive index, and ultraviolet absorption measurements shows that
      the transporters have a trimeric quaternary structure. Limited proteolysis
      further defines regions of primary structure that are exposed to aqueous
      solution. Together, our results define the subunit stoichiometry of high-affinity
      glutamate transporters from B. caldotenax and B. stearothermophilus and localize
      exposed and accessible elements of primary structure. Because of the close amino
      acid sequence relationship between bacterial and eukaryotic transporters, our
      results are germane to prokaryotic and eukaryotic glutamate and neutral amino
      acid transporters.

PMID- 14596614
TI  - Transiently misacylated tRNA is a primer for editing of misactivated adenylates
      by class I aminoacyl-tRNA synthetases.
AB  - The genetic code depends on amino acid fine structure discrimination by aminoacyl
      tRNA synthetases. For isoleucyl- (IleRS) and valyl-tRNA synthetases (ValRS),
      reactions that hydrolyze misactivated noncognate amino acids help to achieve high
      accuracy in aminoacylation. Two editing pathways contribute to aminoacylation
      fidelity: pretransfer and post-transfer. In pretransfer editing, the misactivated
      amino acid is hydrolyzed as an aminoacyl adenylate, while in post-transfer
      editing a misacylated tRNA is deacylated. Both reactions are dependent on a tRNA
      cofactor and require translocation to a site located approximately 30 A from the
      site of amino acid activation. Using a series of 3'-end modified tRNAs that are
      deficient in either aminoacylation, deacylation, or both, total editing (the sum
      of pre- and post-transfer editing) was shown to require both aminoacylation and
      deacylation activities. These and additional results with IleRS are consistent
      with a post-transfer deacylation event initiating formation of an editing-active
      enzyme/tRNA complex. In this state, the primed complex processively edits
      misactivated valyl-adenylate via the pretransfer route. Thus, misacylated tRNA is
      an obligatory intermediate for editing by either pathway.

PMID- 14596615
TI  - Achieving specificity in selected and wild-type N peptide-RNA complexes: the
      importance of discrimination against noncognate RNA targets.
AB  - The boxB RNA pentaloops from the P22 and lambda phages each adopt a GNRA
      tetraloop fold upon binding their cognate arginine-rich N peptides. The third
      loop base in P22 boxB (3-out) and the fourth in lambda boxB (4-out) are excluded
      to accommodate this structure. Previously, we selected a pool of lambda N
      sequences with random amino acids at loop contacting positions 13-22 for binding
      to either of these two GNRA-folded pentaloops or a canonical GNRA tetraloop and
      isolated a class of peptides with a new conserved arginine (R15). Here, we
      characterize the binding of lambda N and these R15 peptides using fluorescent
      titrations with 2-aminopurine labeled versions of the three GNRA-folded loops and
      circular dichroism spectrometry. All peptides preferentially bind the lambda boxB
      RNA loop. lambda N and R15 peptide specificity against the P22 loop arises from
      the cost of rearranging its loop into the 4-out GNRA structure. Modeling
      indicates that the interaction of R8 with an additional loop phosphate in the 4
      out GNRA pentaloop selectively stabilizes this complex relative to the tetraloop.
      R15 peptides gain additional discrimination against the tetraloop because their
      arginine also preferentially interacts with the 4-out GNRA pentaloop phosphate
      backbone, whereas K14 and W18 of lambda N contribute equal affinity when binding
      the tetraloop. Nonspecific electrostatic interactions by basic residues near the
      C-termini of these peptides create significantly steeper salt dependencies in
      association constants for noncognate loops, aiding discrimination at high salt
      concentrations. Our results emphasize the importance of considering specificity
      against noncognate as well as nonspecific targets in the combinatorial and
      rational design of biopolymers capable of macromolecular recognition.

PMID- 14596616
TI  - Effect of the oxidized guanosine lesions spiroiminodihydantoin and
      guanidinohydantoin on proofreading by Escherichia coli DNA polymerase I (Klenow
      fragment) in different sequence contexts.
AB  - Oxidative damage to DNA by endogenous and exogenous reactive oxygen species has
      been directly linked to cancer, aging, and a variety of neurological disorders.
      The potential mutagenicity of the primary guanine oxidation product 8-oxo-7,8
      dihydroguanine (Og) has been studied intensively, and much information is
      available about its miscoding potential in vitro and in vivo. Recently, a variety
      of DNA lesions have been identified as oxidation products of both guanine and 8
      oxoguanine, among them spiroiminodihydantoin (Sp) and guanidinohydantoin (Gh). To
      address questions concerning the mutagenic potential of these secondary products
      of guanine oxidation, the effect of the lesions on proofreading by DNA polymerase
      was studied in vitro using the Klenow fragment of Escherichia coli polymerase I
      (Kf exo+). For the first time, k(cat)/K(m) values were obtained for proofreading
      of the X:N mismatches (X = Og, Gh, or Sp; N = A, G, or C). Proofreading studies
      of the terminal mismatches demonstrated the significance of the sequence context
      flanking the lesion on the 3' side. In addition, a sequence dependence was
      observed for Gh based on the identity of the base on the 5' side of the lesion
      providing evidence for a primer slippage mode if N was complementary to the 5'
      base. Internal mismatches were recognized by Kf exo+ resulting in the excision of
      the correct base pairs flanking mismatches from the 5' side. The absence of a
      sequence effect for the Gh- and Sp-containing duplexes can be attributed to the
      severe destabilization of the lesion-containing duplexes that promotes
      interaction with the exonuclease domain of the Klenow fragment.

PMID- 14596617
TI  - Membrane protein stability: high pressure effects on the structure and
      chromophore-binding properties of the light-harvesting complex LH2.
AB  - Using the bacteriochlorophyll a (Bchl) cofactors as intrinsic probes to monitor
      changes in membrane protein structure, we investigate the response to high
      pressure of the LH2 complexes from the photosynthetic bacteria Rhodobacter
      sphaeroides 2.4.1 and Rhodopseudomonas acidophila 10050. By FT-Raman
      spectroscopy, we demonstrate that high pressure does not induce significant
      distortion of the protein-bound 850 nm-absorbing bacteriochlorophyll molecules,
      or break of the hydrogen bond they are involved in. This indicates in particular
      that the oligomerization of the polypeptides is not perturbed up to 0.6 GPa. The
      pressure-induced changes in the Bchl absorption spectra are attributed to pigment
      pigment interactions. In contrast, the loss of 800 nm-absorbing
      bacteriochlorophyll reflects pressure-induced alterations to the tertiary
      structure of the protein in proximity to the membrane/cytosol interface. This
      suggests that the LH2 protein does have two independent structural domains. The
      first domain is pressure independent and comprises mostly the C-terminal domain.
      The second domain located on the N-terminal side exhibits sensitivity to pressure
      and pH reminiscent of soluble proteins. The LH2 thus constitutes a suitable model
      system for studying in detail the stability of membrane-embedded hydrophobic
      helices and helices located at or close to the solvent/membrane interface.

PMID- 14596618
TI  - Fucoxanthin-chlorophyll proteins in diatoms: 18 and 19 kDa subunits assemble into
      different oligomeric states.
AB  - Fucoxanthin-chlorophyll proteins were purified from the centric diatom Cyclotella
      meneghiniana. Two major fractions were observed that differed in their
      polypeptide composition and oligomeric state. Trimers consist of mainly 18 kDa
      polypeptides. Higher oligomers are tightly assembled from different trimers,
      which contain mostly 19 kDa subunits. In both oligomeric states, the excitation
      energy coupling between fucoxanthin and chlorophyll a was preserved, and
      chlorophyll c was shown to transfer energy efficiently to chlorophyll a. Circular
      dichroism spectra showed close interaction between fucoxanthin and chlorophyll a,
      and different chlorophyll a molecules were demonstrated to interact
      excitonically. The assembly of trimers of antenna proteins with a distinct
      subunit composition into higher oligomeric states was not reported so far and
      differs from the situation found in higher plants. The differences in the
      supramolecular structure of the fucoxanthin-chlorophyll proteins reflect the
      dissimilar arrangement of the thylakoid membranes in diatoms, which lack the
      grana-stroma distinction.

PMID- 14596619
TI  - Transmembrane domain analysis of polycystin-1, the product of the polycystic
      kidney disease-1 (PKD1) gene: evidence for 11 membrane-spanning domains.
AB  - Polycystin-1, the protein product of the polycystic kidney disease-1 (PKD1) gene,
      was originally predicted to be an integral membrane glycoprotein with 11
      transmembrane (TM) domains (TM 1-11). Subsequent comparative sequence analyses
      led to a revision of the original model, which retained the overall topology and
      11 TM segments (TM I-XI) but dropped 3 of the original domains and introduced 3
      new TM domains. The membrane-spanning potential and the orientation of each of
      the proposed TM domains following the extracellular REJ domain (TM I-XI and TM
      11) have now been tested. Using a series of N-terminal polycystin TM
      glycosylation reporter gene fusions expressed in vivo, we assayed N-linked
      glycosylation of the C-terminal glycosylation reporter as an indicator of TM
      domain presence and orientation. This approach has clearly demonstrated that 7 of
      the 12 TM domains tested function as membrane-spanning domains. In vitro analysis
      of the topogenic potential of the five remaining TM domains revealed that four of
      these also function as membrane-spanning domains, thus supporting an 11 TM
      structure for polycystin-1 comprised of TM domains I-XI. In addition, these
      studies suggest that the membrane insertion of TM domains I-IX occurs in a
      cotranslational and sequential manner, while multiple topogenic determinants
      appear to be required for the integration of the C-terminal-most TM segments of
      polycystin-1.

PMID- 14596620
TI  - All three LDL receptor homology regions of the LDL receptor-related protein bind
      multiple ligands.
AB  - The three complete human LDL receptor homology regions of the LDL receptor
      related protein (sLRP2, sLRP3, and sLRP4) have been expressed in Pichia pastoris
      SMD1168 with constitutive coexpression of the receptor-associated protein (RAP).
      Each sLRP was purified to homogeneity after deglycosylation using a combination
      of anion-exchange and size exclusion chromatography. Mass spectrometry and N
      terminal sequencing confirmed the identity of each fragment at purified yields of
      several milligrams per liter. Despite the large number of disulfide linkages and
      glycosylation sites in each LDL receptor homology region (sLRP), all were shown
      to be competent for binding to several LRP1 ligands. Each sLRP also bound human
      RAP, which is thought to be a generalized receptor antagonist, in solution
      binding experiments. As expected, sLRP2 bound the receptor-binding domain of
      alpha(2)-macroglobulin (residues 1304-1451). All three sLRPs bound human
      apolipoprotein-enriched beta very low density lipoprotein, the canonical ligand
      for this receptor. All three sLRPs also bound lactoferrin and thrombin-protease
      nexin 1 complexes. Only sLRP4 bound thrombin-antithrombin III complexes. The
      results show that binding-competent LDL receptor homology regions (sLRPs) can be
      produced in high yield in P. pastoris and readily purified. Each sLRP has binding
      sites for multiple ligands, but not all ligand binding could be competed by RAP.

PMID- 14596621
TI  - NMR structure and dynamics of the second transmembrane domain of the neuronal
      acetylcholine receptor beta 2 subunit.
AB  - Structure and backbone dynamics of a selectively [(15)N]Leu-labeled 28-residue
      segment of the extended second transmembrane domain (TM2e) of the human neuronal
      nicotinic acetylcholine receptor (nAChR) beta(2) subunit were studied by (1)H and
      (15)N solution-state NMR in dodecylphosphocholine micelles. The TM2e structure
      was determined on the basis of the nuclear Overhauser effects (NOEs) and the
      hydrogen bond restraints, which were inferred from the presence of H(alpha)(i)
      H(N)(i+3), H(alpha)(i)-H(beta)(i+3), and H(alpha)(i)-H(N)(i+4) NOE connectivity
      and from the slow amide hydrogen exchange with D(2)O. The TM2e structure of the
      nAChR beta(2) subunit contains a helical region between T4 and K22. Backbone
      dynamics were calculated using the model-free approach based on the (15)N
      relaxation rate constants, R(1) and R(2), and on the (15)N-[(1)H] NOE. The data
      acquired at 9.4 and 14.1 T and calculations using different dynamic models
      demonstrated no conformational exchange and internal motions on the nanosecond
      time scale. The global tumbling time of TM2e in micelles was 14.4 +/- 0.2 ns; the
      NOE values were greater than 0.63 at 9.4 T, and the order parameter, S(2), was
      0.83-0.96 for all (15)N-labeled leucine residues, suggesting a restricted
      internal motion. This is the first report of NMR structure and backbone dynamics
      of the second transmembrane domain of the human nAChR beta(2) subunit in a
      membrane-mimetic environment, providing the basis for subsequent studies of
      subunit interactions in the transmembrane domain complex of the neuronal nAChR.

PMID- 14596622
TI  - Monitoring the early steps of unfolding of dicalcium and mono-Ce3+-substituted
      forms of P43M calbindin D9k.
AB  - Early steps of unfolding of P43M Calbindin D(9k) have been evaluated by NMR
      spectroscopy on the native dicalcium and on the paramagnetic monocerium
      substituted derivative. Although at 2 M GdmHCl the protein core maintains its
      overall folding and structure, amide (15)N R(2) measurements and cross
      correlation rates between N-H dipole-dipole relaxation and (15)N CSA relaxation
      reveal a closer and stronger packing of the hydrophobic interactions in the
      protein as a response to the presence of denaturing agents in solution. A
      complete reorientation of the Met43 side chain toward the hydrophobic core is
      accomplished by the disappearance of the millisecond dynamics observed on the
      native form of Calbindin D(9k), while cross correlation rates provide evidence
      that the two-way hydrogen bond between Leu23 and Val61 is broken or substantially
      weakened. The substitution of the calcium ion in site II with the paramagnetic
      Ce(3+) ion allowed us to obtain a number of long-range nonconventional
      constraints, namely, pseudocontact shifts, which were used, together with the
      NOEs collected on the native state, to monitor subtle structural variations
      occurring in the non-native state of the protein. Although the average rmsd
      between the structures of native and non-native states is small (0.48 A),
      structural rearrangements could be reliably identified. Our results provide
      unprecedented information about the behavior of Calbindin D(9k) during the early
      steps of unfolding. Furthermore, they constitute strong evidence of the
      efficiency of paramagnetism-based constraints in monitoring subtle structural
      changes that are beyond the sensitivity of an approach based only on NOE.

PMID- 14596623
TI  - Can cofactor-binding sites in proteins be flexible? Desulfovibrio desulfuricans
      flavodoxin binds FMN dimer.
AB  - Flavodoxins catalyze redox reactions using the isoalloxazine moiety of the flavin
      mononucleotide (FMN) cofactor stacked between two aromatic residues located in
      two peptide loops. At high FMN concentrations that favor stacked FMN dimers in
      solution, isothermal titration calorimetric studies show that these dimers bind
      strongly to apo-flavodoxin from Desulfovibrio desulfuricans (30 degrees C, 20 mM
      Hepes, pH 7, K(D) = 5.8 microM). Upon increasing the temperature so the FMN
      dimers dissociate (as shown by (1)H NMR), only one-to-one (FMN-to-protein)
      binding is observed. Calorimetric titrations result in one-to-one binding also in
      the presence of phosphate or sulfate (30 degrees C, 13 mM anion, pH 7, K(D) = 0.4
      microM). FMN remains dimeric in the presence of phosphate and sulfate, suggesting
      that specific binding of a divalent anion to the phosphate-binding site triggers
      ordering of the peptide loops so only one isoalloxazine can fit. Although the
      physiological relevance of FMN and other nucleotides as dimers has not been
      explored, our study shows that high-affinity binding to proteins of such dimers
      can occur in vitro. This emphasizes that the cofactor-binding site in flavodoxin
      is more flexible than previously expected.

PMID- 14596624
TI  - Detailed dissection of a new mechanism for glycoside cleavage: alpha-1,4-glucan
      lyase.
AB  - The unusual enzyme, Gracilariopsis alpha-1,4-glucan lyase of the sequence-related
      glycoside hydrolase family 31, cleaves the glycosidic bond of alpha-1,4-glucans
      via a beta-elimination reaction involving a covalent glycosyl-enzyme intermediate
      (Lee, S. S., Yu, S., and Withers, S. G. (2002) J. Am. Chem. Soc. 124, 4948-4949).
      The classical bell-shaped pH dependence of k(cat)/K(m) indicates two ionizable
      groups in the active site with apparent pK(a) values of 3.05 and 6.66. Bronsted
      relationships of log k(cat) versus pK(a) and log(k(cat)/K(m)) versus pK(a) for a
      series of aryl glucosides both show a linear monotonic dependence on leaving
      group pK(a) with low beta(lg) values of 0.32 and 0.33, respectively. The
      combination of these low beta(lg) values with large secondary deuterium kinetic
      isotope effects (k(H)/k(D) = 1.16 - 1.19) on the first step indicate a
      glycosylation step with substantial glycosidic bond cleavage and proton donation
      to the leaving group oxygen at the transition state. Developed oxocarbenium ion
      character of the transition state is also suggested by the potent inhibition
      afforded by acarbose and 1-deoxynojirimycin (K(i) = 20 and 130 nM, respectively)
      and by the substantial rate reduction afforded by adjacent fluorine substitution.
      For only one substrate, 5-fluoro-alpha-D-glucopyranosyl fluoride, was the second
      elimination step shown to be rate-limiting. The large alpha-secondary deuterium
      kinetic isotope effect (k(H)/k(D) = 1.23) at C-1 and the small primary deuterium
      kinetic isotope effect (k(H)/k(D) = 1.92) at C-2 confirm an E2 mechanism with
      strong E1 character for this second step. This considerable structural and
      mechanistic similarity with retaining alpha-glucosidases is clear evidence for
      the evolution of an enzyme mechanism within the family.

PMID- 14596625
TI  - Glycosaminoglycans bind factor Xa in a Ca2+-dependent fashion and modulate its
      catalytic activity.
AB  - Recent studies have demonstrated the existence of a Ca(2+)-dependent heparin
      binding site on factor Xa. To characterize this heparin-binding site, the
      extrinsic fluorescence of fluorescein-labeled, active site-blocked factor Xa was
      monitored as it was titrated with glycosaminoglycans of various sulfate content
      and chain length. The binding of glycosaminoglycans to factor Xa appears to be
      charge-dependent because affinity is correlated with degree of glycosaminoglycan
      sulfation. All glycosaminoglycans bind factor Xa with higher affinity in the
      presence of Ca(2+) than in its absence. In contrast, when Gla-domainless factor
      Xa was substituted for factor Xa, glycosaminoglycans bound with similar
      affinities in the absence and presence of Ca(2+). These results support the
      hypothesis that the anionic Gla domain impairs glycosaminoglycan binding in the
      absence of Ca(2+). The changes in fluorescence intensity of factor Xa when
      titrated with glycosaminoglycans suggest that glycosaminoglycans induce
      conformational changes in the active site environment of factor Xa. To explore
      the consequences of these conformational changes, the effect of
      glycosaminoglycans on the catalytic activity of factor Xa was examined.
      Glycosaminoglycans influenced the ability of factor Xa to cleave chromogenic
      substrates and attenuated the capacity of factor Xa to activate factor VII. The
      potency of glycosaminoglycans in these assays reflected their affinity for factor
      Xa. These studies suggest that glycosaminoglycan binding perturbs exosites on the
      surface of factor Xa, potentially modifying interactions with cofactors or
      substrates.

PMID- 14596626
TI  - Evaluating minimal clinically important differences for the acne-specific quality
      of life questionnaire.
AB  - BACKGROUND: The Acne-Specific Quality of Life Questionnaire (Acne-QoL) is a
      responsive, reliable and valid instrument developed to measure the impact of
      facial acne across four dimensions of patient QOL. Score changes on this
      instrument have been used to report statistically significant treatment
      advantages for a low-dose oral contraceptive (Estrostep, containing
      norethisterone (norethindrone) acetate (NA) 1mg and ethinylestradiol (EE) [20,
      30, 35 mg] as compared with placebo in women with moderate acne vulgaris.
      However, the question remained if these statistically significant results were
      also clinically meaningful. OBJECTIVES: To evaluate the statistically significant
      Acne-QoL benefits observed with NA/EE in terms of their clinical significance,
      and to compare the three different approaches for defining a minimal clinically
      important difference (MCID) for the Acne-QoL instrument. METHODS: Since the
      optimum method for estimating MCIDs has yet to be established, three different
      published approaches for determining MCIDs were applied and compared using data
      from two randomised, double-blind, placebo- controlled studies of the efficacy of
      NA/EE in the treatment of facial acne. RESULTS: Although the approaches differed
      substantially, the resulting MCID estimates were comparable. Specifically, the
      MCID estimates ranged from 0.50-10.3 mean change per item, depending on the
      domain. The results showed that the statistically significant treatment
      advantages for NA/EE were also clinically significant. CONCLUSION: When applied
      to the change scores present, the results showed that the statistically
      significant treatment advantages for NA/EE were also clinically significant.

PMID- 14596627
TI  - Frequency of hospitalisations and inpatient care costs of manic episodes: in
      patients with bipolar I disorder in France.
AB  - BACKGROUND: Bipolar disorder is a chronic illness that may involve multiple
      relapses and result in substantial psychosocial impairment. However, very few
      recent studies have investigated the economic burden of the disease. OBJECTIVE:
      To assess the frequency of hospitalisation and the inpatient care costs
      associated with manic episodes in patients with bipolar I disorder in France.
      METHOD: A cost-of-illness study was conducted based on available data using a
      hospital payer perspective. The lifetime prevalence of manic episodes was
      estimated from published epidemiological data using a random-effects meta
      analysis. Data were obtained by a computerised literature search using the main
      scientific and medical databases. Additional epidemiological references were
      identified from published studies and textbooks. Data on frequency of
      hospitalisation and length of stay were collected from a large psychiatric
      university hospital. Data on unit costs for inpatient care were obtained from the
      accounting system of the largest hospital group in Paris, France for the year
      1999. RESULTS: Extrapolating from international data on the average prevalence of
      bipolar I disorder, the proportion of rapid cycling patients and the average
      cycle duration, we estimated the annual number of manic episodes in patients with
      bipolar I disorder to be around 265,000 in France. Based on hospital data in
      Paris, the proportion of manic episodes that require hospitalisation was
      estimated to be around 63%. The average length of stay was 32.4 days and the
      hospitalisation-related costs were estimated to be around 8.8 billion French
      francs (Euro 3 billion) [1999 values]. CONCLUSION: Our study highlights the lack
      of medical and economic data on the frequency and hospitalisation-related costs
      of manic episodes in patients with bipolar I disorder in France. As the lifetime
      prevalence of bipolar I disorder may be as high as 3% among adults, further
      studies are required in order to provide representative national data and to
      allow economic evaluations of costs related to bipolar I disorder in France.

PMID- 14596628
TI  - Heartburn in patients with gastro-oesophageal reflux disease in Germany and
      Sweden: a study on patients' burden of disease.
AB  - BACKGROUND: Gastro-oesophageal reflux disease (GORD) is widespread in the general
      population and presents in most cases with heartburn as the main symptom. The
      severity of symptoms is not necessarily related to erosive damage to the
      oesophagus due to acid reflux, but the frequency and severity of symptoms have an
      impact on the health-related QOL (HR-QOL) of the patient. OBJECTIVE: To
      characterise patients with GORD who consult a physician because of heartburn with
      respect to medical background and burden of disease in Germany and Sweden.
      METHODS: A total of 1011 patients who had been experiencing symptoms of GORD,
      including heartburn, for at least 1 year were recruited by physicians, who
      collected data on the patients' previous diagnosis and treatment. The patients
      themselves were interviewed by telephone about their heartburn. The EuroQOL 5
      dimensional HR-QOL questionnaire (EQ-5D) and the Gastrointestinal Symptom Rating
      Scale (GSRS) were used to measure patient-reported outcomes. RESULTS: About half
      of the patients had been experiencing symptoms of GORD for >5 years. The majority
      (54%) perceived the severity of their heartburn as moderate. Thirty-eight percent
      of the patients had been examined by endoscopy during the last 12 months and 79%
      of these had macroscopic oesophagitis. Medical treatment for heartburn had been
      prescribed to 88% of the patients. The mean annual number of days with heartburn
      was assessed as 170 days per patient, with the majority of patients (64%)
      experiencing heartburn every week. HR-QOL was reduced in these patients as
      expressed by EQ-5D scores compared to scores for a general population. Patients
      with GORD had problems related to gastrointestinal symptoms as rated by GSRS
      scores. More severe heartburn was associated with a greater number of symptom
      days and reduced HR-QOL scores, whereas a relationship between the findings at
      endoscopy and the severity of symptoms or HR-QOL could not be found. CONCLUSION:
      This study demonstrates that heartburn confers a significant burden on patients
      with GORD, related to the frequency and severity of symptoms and reflected in the
      reduction in HR-QOL as perceived by the patients.

PMID- 14596629
TI  - Methods to analyse cost data of patients who withdraw in a clinical trial
      setting.
AB  - BACKGROUND: Missing data resulting from premature study withdrawal are a common
      problem in the analysis of longitudinal data in clinical trials. To date, this
      subject has received little attention in the context of economic evaluations and
      with regard to the analysis of cost data. OBJECTIVES: To (i) demonstrate the
      impact of patients who drop out during the study on the outcomes of an economic
      evaluation, and (ii) to compare the mean and variation in costs after applying
      five different methods to deal with incomplete data: multiple imputation,
      complete cases analysis, linear extrapolation, predicted mean and hot decking.
      STUDY DESIGN: The study was performed using cost data collected in two randomised
      clinical trials comparing patients with chronic obstructive pulmonary disease
      receiving either tiotropium bromide or ipratropium bromide. The overall dropout
      rate was 17%, with the daily costs of the dropouts approximately 4 times higher
      than the costs of the completers. METHODS: Multiple imputation is a principled
      method that deals with missing observations by replacing each missing observation
      with a set of multiple plausible values. The variance between the resulting
      multiple datasets is combined with the variance between the datasets to take
      account of the extra uncertainty that results from missing data. The outcomes
      after multiple imputation were compared with the results of four naive methods to
      deal with missing observations: complete cases analysis, linear extrapolation,
      predicted mean and hot decking. All costs were expressed in 2001 euros. RESULTS:
      In the tiotropium bromide group, mean (standard error) costs varied from Euro 955
      (137) after complete cases analysis to Euro 1298 (198) after linear
      extrapolation. The corresponding estimates in the ipratropium bromide group were
      Euro 970 (125) and Euro 1561 (244), respectively. The difference in costs between
      treatment groups varied from -Euro 15 (95% CI: -379 to 349) after complete cases
      analysis to -Euro 402 (95% CI: -883 to 79) after predicted mean, in favour of the
      tiotropium bromide group. The difference in costs according to the other methods
      varied from -Euro 263 (95% CI: -878 to 353) after linear extrapolation to -Euro
      265 (95% CI: -709 to 180) after multiple imputation to -Euro 359 (95% CI: -771 to
      54) after hot decking. CONCLUSION: This study showed that the method of dealing
      with the data of the dropouts had a large impact on the outcomes of an economic
      evaluation. Information about the rate of patient withdrawal and the way data of
      dropouts are treated is of vital importance in assessing the results of economic
      evaluations and should always be reported. Multiple imputation is a principled
      method that can be used to deal with the data of these patients.

PMID- 14596630
TI  - Indirect costs in ambulatory patients with HIV/AIDS in Spain: a pilot study.
AB  - OBJECTIVE: To estimate indirect costs in Spanish ambulatory patients with
      HIV/AIDS and to identify changes in employment status and their current QOL.
      METHOD: Information was obtained through 32 interviews/enquiries carried out with
      ambulatory patients receiving medical attention at Gregorio Maranon and Puerta de
      Hierro hospitals in Madrid, Spain. The study variables included information on
      sociodemographics, economics, and clinical and QOL (EuroQol instrument; EQ-5D)
      parameters of these patients. RESULTS: Our main result showed the existence of
      high indirect costs (lost income and lost wages; 2002 values) at the individual
      level. We identified a strong effect in terms of income loss (the annual loss of
      income ranged between Euro 5271 and Euro 6150 per patient) and lost wages (the
      annual loss of wages ranged between Euro 7537 and Euro 8793 per patient). We also
      observed a strong impact on household income (the annual loss of household income
      ranged between Euro 6693 and Euro 7813). There was a great variability in these
      costs among the patients depending on their QOL, gender and education. We
      detected a statistically significant and positive correlation between QOL and
      having a job. CONCLUSIONS: We observed a high level of QOL among the patients,
      which reflects the potential benefits of pharmacological treatment. We found that
      the better the QOL, the higher the probability of being employed. However,
      indirect costs were high among patients despite their good QOL.

PMID- 14596631
TI  - Reductions in individual work productivity associated with type 2 diabetes
      mellitus.
AB  - BACKGROUND: Chronic diseases and their treatments may cause symptoms that impair
      performance but are too mild to affect outcome measures such as absences and
      workforce exit. OBJECTIVE: To assess the effect of type 2 diabetes mellitus on
      individuals' productivity when working, absences from work and the value of any
      lost work time. METHODS: Subjects were identified from claims data and enrolled
      over the phone. A telephone survey was used to elicit information about
      productivity at work, absences, diabetes history, comorbidities, job
      characteristics, employment history, demographics and healthcare utilisation. The
      sample consisted of 472 employed residents of New York state, USA, of whom, 445
      worked at one major US corporation. Of the 472 participants, 78 had type 2
      diabetes. All participants agreed to release their claims data for this study;
      participants with diabetes also consented to the release of clinical records. All
      data were linked at the individual level. Tobit regression was used to model work
      efficiency losses, the total productivity time lost and the value of that time.
      Absences were modelled using Poisson regression. Productivity was measured using
      absences from work and work efficiency. Work efficiency was assessed using the
      Osterhaus model. MAIN OUTCOME MEASURES AND RESULTS: Using the Osterhaus model of
      work productivity, type 2 diabetes was associated with a reduction in
      productivity at work. These productivity losses increased with the length of
      exposure to diabetes. Surprisingly, higher productivity losses among employees
      with diabetes did not translate into significantly higher productivity costs
      because the group with diabetes earned less. This likely reflects the prevalence
      of diabetes in populations. Among salaried people, very few reported working
      extra hours to make up for reduced productivity. Self-report biases may have been
      a factor in this finding. Type 2 diabetes was not associated with more frequent
      absences. Other factors that have strong effects on work efficiency are
      depression and colds, and job satisfaction. CONCLUSIONS: People with type 2
      diabetes appear to experience incremental decrements in work performance that may
      affect their current and future health and performance. Lower incomes of
      participants with diabetes suggest that both people with diabetes and their
      employers bear the cost of any work efficiency losses.

PMID- 14596632
TI  - The potential and limitations of personalized medicine in the doctor-patient
      relationship.

PMID- 14596635
TI  - Visualizing biological complexity.

PMID- 14596633
TI  - Pharmacogenetics and public policy: expert views in Europe and North America.
AB  - The new genetics is stimulating the development of genetic testing of patients to
      help choose the best drug, adjust doses and avoid side effects. Proponents say
      that this personalized medicine will revolutionize drug development and
      healthcare. In a series of group meetings, 48 leading experts from regulatory
      agencies, industry, academia and consumer interests gave their opinions on the
      public policy priorities. Most believed that pharmacogenetics would have a clear
      impact on care within 15 years and that a public policy response was needed. The
      establishment of a good clinical evidence base should be a priority, together
      with addressing the needs of drug response gene minorities. A total of 72% also
      believed that postmarketing surveillance systems should be collecting DNA from
      patients experiencing moderate or severe adverse events.

PMID- 14596636
TI  - Pharmacogenomics of diuretic drugs: data on rare monogenic disorders and on
      polymorphisms and requirements for further research.
AB  - This review summarizes the current status of our knowledge about the role of
      pharmacogenetic variation in response to diuretics and suggests future research
      topics for the field. Genes with a role in the pharmacokinetics of most diuretics
      are renal drug transporters, especially OAT1, OAT3 and OCT2 (genes SLC22A6,
      SLC22A8 and SLC22A2) whereas variants in carbonic anhydrase (CA), cytochrome P450
      enzymes and sulfotransferases are relevant only for specific substances. Genes on
      the pharmacodynamic side include the primary targets of thiazide, loop, K(+)
      sparing and aldosterone antagonistic diuretics: NCC, NKCC2, ENaC and the
      mineralocorticoid receptor (genes SLC12A3, SLC12A1, SCNN1A, B, G and NR3C2). Rare
      variants of these proteins cause Gitelman's syndrome, Bartter's syndrome,
      Liddle's syndrome or pregnancy-induced hypertension. Polymorphisms in these and
      in associated proteins such as GNB3, alpha-adducin and angiotensin-converting
      enzyme (ACE) seem to be clinically relevant. In conclusion, first knowledge has
      evolved that efficacy of diuretic drugs may be determined by genetic
      polymorphisms in genes determining pharmacokinetics and pharmacodynamics of this
      drug class. In the future, the selection of a diuretic drug or the dosing
      schedules may be individually chosen based on pharmacogenetic parameters,
      however, many questions remain to be answered before this fantasy becomes
      reality.

PMID- 14596637
TI  - Applications of genomics in the inner ear.
AB  - Understanding the development and function of the inner ear requires knowledge of
      the genes expressed and the pathways involved. Such knowledge is also essential
      for the development of therapeutic approaches for a wide range of inner ear
      diseases affecting millions of people. The completion of the Human Genome Project
      and emergence of genomics-based technologies have made it possible to analyze the
      expression patterns of the inner ear genes at the whole genome level, generating
      an unprecedented amount of information on gene expression patterns. This review
      will discuss the current status of work using genomics, in particular the
      functional genomics approach, to study different aspects of inner ear genes. It
      will also illustrate how the approach can help to identify and characterize
      deafness genes, as well as contributing to work related to hair cell
      regeneration.

PMID- 14596639
TI  - Pharmacogenetic candidate genes for melanoma.
AB  - The incidence of melanoma is rising at an alarming rate and has become an
      important public health concern. If detected early, melanoma carries an excellent
      prognosis after appropriate surgical resection. Unfortunately, advanced melanoma
      has a poor prognosis and is notoriously resistant to radiation and chemotherapy.
      The relative resistance of melanoma to a wide-range of chemotherapeutic agents
      and high toxicity of current therapies has prompted a search for effective
      alternative treatments that would improve prognosis and limit side effects.
      Advances in molecular genetics are revealing in increasing detail the mechanisms
      responsible for the development of melanoma. Hopefully, elucidation of these
      pathways will provide a means of screening high-risk individuals and allow new
      drug development for prevention and treatment by identification of specific
      pharmacological targets. This review will summarize the genetics of melanoma with
      the goal of providing insights into potential pharmacogenetic candidate genes.

PMID- 14596638
TI  - Pharmacogenomics in the treatment of epilepsy.
AB  - Genetic variability has recently been implicated in the development of familial
      epilepsy syndromes and in heterogeneous responses of epilepsy patients to drug
      treatment. Mutations in distinct proteins have been shown to underlie the
      development of epilepsy, increase propensity for drug resistance, and alter drug
      metabolism. Improved understanding of how individual genetic variability may
      alter the efficacy of pharmacological therapeutic interventions is an important
      and timely goal. The investigation of relationships between genotype and patient
      responses to drug treatment is termed pharmacogenomics.

PMID- 14596640
TI  - Pharmacogenetic aspects in treatment of colorectal cancer--an update.
AB  - Pharmacogenomic analyses will become crucial to predict patients' toxicity to
      treatment and will also help to predict the tumor response. Processes of drug
      metabolism, drug efflux, DNA-repair and characteristics of drug targets are
      critical checkpoints of drug efficacy. These crucial pathways for drug action
      have been part of pharmacogenomic studies evaluating the impact of genomic
      variants on transcription, translation, protein structure and substrate binding
      of the genes involved. Promising candidates have been identified with predictive
      value for response and toxicity to chemotherapy in colorectal cancers. These
      candidates need to be incorporated into large, prospective clinical trials to
      confirm their impact for response and survival to chemotherapy that has been
      reported in retrospective analyses. Confirmed predictive markers, together with
      additional yet to be identified pharmacogenomic key players, will provide the
      basis for tailoring chemotherapy in the future.

PMID- 14596641
TI  - Genome-wide evaluation of the public SNP databases.
AB  - The public SNP databases are an important resource for groups performing genetic
      association and linkage studies. Both academic and commercial groups are
      developing large numbers of genotyping assays for SNPs in candidate genes or
      spread across the genome. These databases now contain in excess of 6 million SNPs
      that have been generated using a large number of methods and cohorts. Today,
      however, only a small fraction of these SNPs are well characterized and
      validated. The latest release of dbSNP contains approximately 3.7 million non
      redundant entries, only 0.5 million of which are validated, and 0.2 million of
      which have frequency information. Users of these databases have several common
      questions. How many of the SNPs are real? What is the frequency spectrum of the
      SNPs in these databases? What is the distribution picture of these SNPs across
      different ethnic and geographical populations? What fraction of the total number
      of SNPs is already captured by these databases? In order to address these
      questions, we compared the public SNPs against a well-characterized collection of
      gene-centric SNPs that we have developed. From this comparison, we find that >
      50% of high frequency SNPs in the genome (> 20% minor allele frequency) have
      already been captured by these databases. The coverage drops dramatically below
      frequencies of 10%. At high frequencies, there is no sampling bias with respect
      to ethnicity or to regions of the genome. Finally, a relatively large fraction (>
      40%) of SNPs in these databases were not seen in our study, which means that they
      are either of very low frequency, mismapped, or not polymorphic at all.

PMID- 14596642
TI  - In vivo multi-tissue corticosteroid microarray time series available online at
      Public Expression Profile Resource (PEPR).
AB  - Gene microarrays are becoming a key tool for the analysis of changes in gene
      expression in a variety of conditions. Use of microarrays to analyze drug
      responses has mainly been restricted to comparing treated versus untreated
      samples at a few time points. Such data do not permit the use of another
      important tool, pharmacokinetic/pharmacodynamic (PK/PD) modeling. Such modeling
      requires the simultaneous analysis of pharmacokinetic data along with time series
      data on dynamic responses. This report describes data obtained from two extended
      microarray time series (rat liver and skeletal muscle) for the in vivo responses
      to a single bolus dose of methylprednisolone that are uniquely available online
      in a single gene query format. Use of these data does not require any a priori
      knowledge or software normally necessary for the analysis of microarray data.
      Since the pharmacokinetic data and receptor model have been published, the
      results are amenable to PK/PD and pharmacogenomic evaluation.

PMID- 14596643
TI  - Information on commercial aspects of pharmacogenomics.

PMID- 14596644
TI  - GAG BioScience GmbH.
AB  - Completion of the human genome project led to an explosion in available genomic
      information. Single nucleotide polymorphisms (SNPs) have emerged as a versatile
      and powerful tool for genotyping almost all variant species. The unique
      technological platform developed by GAG BioScience is exclusively based on SNP
      detection and allows genotyping of up to 60,000 samples per day. An analysis
      robot, a mass spectrometer and a database form a practically self-controlled
      analysis and documentation system that achieves high-throughput rates of samples
      with absolute precision. By using a Laboratory Information and Management System,
      up to 150 million genotypes can be simultaneously retrieved and stored. In
      cooperation with a partner, GAG BioScience develops new and powerful tools for
      further data analysis.

PMID- 14596645
TI  - Review of the current management of atrial fibrillation.
AB  - Atrial fibrillation (AF) is the most common sustained arrhythmia. Its prevalence
      is increasing and accordingly, so is its burden on healthcare systems throughout
      the world. The pathophysiology of AF is complex and poorly understood, which of
      itself presents a major challenge to the management of this important condition.
      AF is associated with increased morbidity and mortality, particularly in patients
      with underlying left ventricular dysfunction. Once AF occurs, it is often
      difficult to 'cure' and as such, the major focus of therapy is currently divided
      essentially between a rate control strategy and a need to revert to and maintain
      sinus rhythm. Both approaches seek to minimise the associated symptoms and
      complications. Over the past two decades, numerous pharmacological approaches to
      the management of AF have been employed, many of which have been shown to be
      relatively ineffective or confounded by major complications. Accordingly, recent
      research and interest has focused on non-pharmacological electrophysiological
      therapies to either cure AF or improve symptoms. This review summarises the
      current approaches to the management AF and provides some new insights into
      emerging therapies for this common clinical problem.

PMID- 14596646
TI  - Pharmacotherapy for dyslipidaemia--current therapies and future agents.
AB  - Current lipid-altering agents that lower low density lipoprotein cholesterol (LDL
      C) primarily through increased hepatic LDL receptor activity include statins,
      bile acid sequestrants/resins and cholesterol absorption inhibitors such as
      ezetimibe, plant stanols/sterols, polyphenols, as well as nutraceuticals such as
      oat bran, psyllium and soy proteins; those currently in development include newer
      statins, phytostanol analogues, squalene synthase inhibitors, bile acid transport
      inhibitors and SREBP cleavage-activating protein (SCAP) activating ligands. Other
      current agents that affect lipid metabolism include nicotinic acid (niacin),
      acipimox, high-dose fish oils, antioxidants and policosanol, whilst those in
      development include microsomal triglyceride transfer protein (MTP) inhibitors,
      acylcoenzyme A: cholesterol acyltransferase (ACAT) inhibitors, gemcabene,
      lifibrol, pantothenic acid analogues, nicotinic acid-receptor agonists, anti
      inflammatory agents (such as Lp-PLA(2) antagonists and AGI1067) and functional
      oils. Current agents that affect nuclear receptors include PPAR-alpha and -gamma
      agonists, while in development are newer PPAR-alpha, -gamma and -delta agonists,
      as well as dual PPAR-alpha/gamma and 'pan' PPAR-alpha/gamma/delta agonists. Liver
      X receptor (LXR), farnesoid X receptor (FXR) and sterol-regulatory element
      binding protein (SREBP) are also nuclear receptor targets of investigational
      agents. Agents in development also may affect high density lipoprotein
      cholesterol (HDL-C) blood levels or flux and include cholesteryl ester transfer
      protein (CETP) inhibitors (such as torcetrapib), CETP vaccines, various HDL
      'therapies' and upregulators of ATP-binding cassette transporter (ABC) A1,
      lecithin cholesterol acyltransferase (LCAT) and scavenger receptor class B Type 1
      (SRB1), as well as synthetic apolipoprotein (Apo)E-related peptides. Fixed-dose
      combination lipid-altering drugs are currently available such as extended-release
      niacin/lovastatin, whilst atorvastatin/amlodipine, ezetimibe/simvastatin,
      atorvastatin/CETP inhibitor, statin/PPAR agonist, extended-release
      niacin/simvastatin and pravastatin/aspirin are under development. Finally,
      current and future lipid-altering drugs may include anti-obesity agents which
      could favourably affect lipid levels.

PMID- 14596647
TI  - Recent advances in the pharmacotherapy for hyperbilirubinaemia in the neonate.
AB  - Jaundice is a common cause for diagnostic works-up and therapeutic intervention
      in neonates. This is motivated by the risk for severe neurological sequelae
      (kernicterus). The mainstays of treatment for the past decades have been exchange
      transfusion and phototherapy. Exchange transfusion is now becoming rare due to
      immune prophylaxis in Rhesus-negative women, and treatment of sensitised infants
      with intravenous immunoglobulin. Several different pharmacological approaches
      have been studied as far as the treatment of neonatal jaundice. Of these, the
      focus of attention in recent years has been on the haem oxygenase inhibitors
      (metal meso- and protoporphyrins). These are effective inhibitors of bilirubin
      production and have been shown to significantly reduce peak serum bilirubin
      levels in several clinical trials, both when used prophylactically and
      therapeutically. However, questions remain regarding long-term safety, as well as
      the advisability of whole-scale inhibition of bilirubin production. Nevertheless,
      in selected infants with a high risk of severe jaundice, the use of haem
      oxygenase inhibitors may be acceptable. Pharmacotherapy in jaundiced infants is
      fraught with risks, as many drugs may increase the entry of bilirubin into the
      brain and presumably, the risk for neurotoxicity. Both the displacement of
      bilirubin from its albumin binding and interference with the function of
      phosphoglycoprotein in the blood-brain barrier are documented mechanisms in this
      respect.

PMID- 14596648
TI  - The use of mycophenolate mofetil in liver transplant recipients.
AB  - Mycophenolate mofetil is an important drug in the modern immunosuppressive
      arsenal. Mycophenolate mofetil is the semisynthetic morpholinoethyl ester of
      mycophenolate acid. Mycophenolate acid prevents T and B cell proliferation by
      specifically inhibiting a purine pathway required for lymphocyte division. This
      paper extensively reviews the experience of mycophenolate mofetil use in liver
      transplant recipients. In randomised trials, mycophenolate mofetil decreased the
      rate of acute rejection after liver transplantation, without a significant
      increase of septic complications. However, so far, there are no data indicating
      that mycophenolate mofetil increases liver transplant patient or graft survivals.
      Mycophenolate mofetil is interesting because of its particular side effects
      profile, which is very different from the other immunosuppressants. The absence
      of mycophenolate mofetil nephrotoxicity is of specific interest in liver
      recipients with impairment of renal function. The monitoring of mycophenolate
      acid area under the concentration time curve might be interesting to limit side
      effects and provide better clinical efficacy but the exact role of mycophenolate
      acid monitoring in liver recipients has yet to be further evaluated in large
      series.

PMID- 14596649
TI  - Vesicoureteral reflux--current treatment options.
AB  - Vesicoureteral reflux has long been recognised as a major child and public health
      problem. Widespread recognition and screening of at-risk populations has the
      potential to significantly reduce long-term morbidity in both children and
      adults. Advances in pharmacotherapy, materials science and surgery, have caused
      many experts to reassess established dictums of treatment. Concern regarding the
      overuse of antibiotics and surgery has led to efforts to tailor therapy more
      narrowly for those who are at the highest risk from recurrent urinary tract
      infection and pyelonephritis. Children after a certain age, without underlying
      voiding dysfunction, might not require treatment at all. Newer surgical and
      anaesthetic techniques have the potential of transforming surgical correction
      from a painful experience to an ambulatory procedure, with a rapid return to
      daily activities. Both the promise and pitfalls of these newest advances will be
      discussed in this review.

PMID- 14596650
TI  - Current status in the pharmacological management of interstitial cystitis.
AB  - Interstitial cystitis is a clinical condition occurring predominantly in women
      characterised by irritative voiding symptoms in the form of urinary frequency,
      urgency and pain. Patient symptoms have the potential to significantly affect
      quality of life, posing a challenge to some to perform activities of daily
      living. Those who reach an eventual diagnosis of interstitial cystitis have
      typically done so through an emotionally charged and circuitous route, the
      product of numerous physician encounters and stigmatising experiences. As such,
      these patients require considerate care. Overall, current pharmacological agents
      for the treatment of those with interstitial cystitis, provide a measure of
      symptomatic benefit, however, a universally effective regimen remains to be
      reported. As a definitive disease aetiopathogenesis is not fully determined,
      trials of pharmacological therapy are ongoing.

PMID- 14596651
TI  - Growth hormone replacement for adult growth hormone deficiency.
AB  - Growth hormone deficiency (GHD) in childhood causes growth retardation, short
      stature and significant impairment of adult height. Growth hormone (GH) has been
      given successfully to these children for > 40 years but only since the
      introduction of recombinant DNA technology, has enough GH been available for
      paediatric needs and also for other indications. Adults with pituitary disease
      and hypopituitarism commonly develop GHD. Adult GHD is associated with an array
      of body composition alterations and metabolic abnormalities, as well as impaired
      physical performance and psychological well-being. None of these abnormalities
      are pathogenic for GHD but they constitute a characteristic clinical syndrome. GH
      substitution for adult GHD has been approved since 1996 in the US and most
      Western countries and since then, the clinical experience with this novel
      therapeutic modality is exponentially increased. GH replacement in this
      population has resulted in considerable clinical benefits. This article reviews
      the therapeutic principles, available GH formulations and current treatment
      guidelines for adult patients with GHD.

PMID- 14596652
TI  - Treatment of female infertility with recombinant human luteinising hormone: is
      there a benefit over other available drugs?
AB  - This manuscript reviews the role of recombinant human luteinising hormone (rhLH)
      as a therapeutic drug in ovarian stimulation for assisted reproductive technology
      (ART) and ovulation induction. For this purpose, the role of LH during the
      follicular phase and during the ovulatory surge, along with the role of human
      chorionic gonadotropin (hCG) as a surrogate LH, is reviewed and compared to the
      results available with the new rhLH formulation. The use of rhLH was found to be
      safe and highly effective given during the follicular phase and to mimic an
      endogenous LH surge. The availability of both LH and follicle stimulating hormone
      (FSH) as separate recombinant preparations enables physicians to adjust the doses
      of each gonadotropin to the individual patient according to the 'therapeutic
      window' concept for each drug to maximise the success of ovarian stimulation.

PMID- 14596653
TI  - Ovulation induction.
AB  - Anovulation, a common cause of female infertility, is a highly curable condition.
      Presented here is a simple treatment-orientated diagnostic scheme. Anovulatory
      women with low endogenous oestradiol and follicle stimulating hormone (FSH) are
      treated with either pulsatile gonadotrophin releasing hormone (GnRH) or
      gonadotropins, and women with eu-oestrogenic anovulation (mostly with polycystic
      ovarian syndrome; PCOS) have first-line treatment with clomiphene citrate (CC),
      possibly with metformin. If CC fails, FSH is administered using a chronic low
      dose protocol with small incremental dose rises. A comparison of urinary with
      recombinant and pure FSH with luteinising hormone (LH) containing gonadotropins
      is made. Recombinant products are purer and more convenient for use but are
      expensive. LH content has little impact except in hypogonadotropic hypogonadism
      or severe pituitary suppression with GnRH analogues. Aromatase inhibitors,
      recombinant LH and long-acting FSH may find a future place in the armamentarium.

PMID- 14596654
TI  - Pharmacotherapy of gestational trophoblastic disease.
AB  - Gestational trophoblastic neoplasms are the most responsive of all solid tumours
      to chemotherapy leading to an overall cure rate of > 90%. Non-metastatic disease
      (FIGO Stage I) and low-risk metastatic disease (FIGO Stages II and III; WHO score
      < 7) can be treated with single-agent methotrexate or actinomycin D protocols
      resulting in a survival rate approaching 100%. Metastatic high-risk disease (FIGO
      Stage IV or WHO score > 7) should be treated with initial intensive multimodality
      therapy with combination chemotherapy, consisting of etoposide, high-dose
      methotrexate, actinomycin D, cyclophosphamide and vincristine (EMA-CO) and
      adjuvant radiotherapy and surgery when indicated. Despite this aggressive
      approach, approximately 30% of patients with high-risk disease will fail initial
      therapy or relapse from remission. Salvage chemotherapy with drug regimens
      containing platinum agents and etoposide, usually in conjunction with bleomycin
      or ifosfamide, as well as surgical resection of sites of resistant disease, will
      ultimately result in a survival rate of 80 - 90% for metastatic high-risk
      disease.

PMID- 14596655
TI  - Cost-assessment of alternative management strategies for achalasia.
AB  - Achalasia is a primary oesophageal motor disorder characterised by the abnormal
      relaxation of the lower oesophageal sphincter (LES) and absent oesophageal
      peristalsis. It is a rare disease, with an estimated incidence of approximately
      1/100,000 and a prevalence close to 10/100,000 [1]. Its exact aetiology remains
      unknown. Autoimmune, infectious, degenerative and hereditary processes have all
      been proposed as factors that lead to a chronic inflammatory response in the
      myenteric plexus, thus resulting in selective loss of inhibitory neurons [2] and
      failure of the LES to relax and aperistalsis in the body of the oesophagus. The
      most common symptoms of achalasia are dysphagia for solids and liquids,
      regurgitation, chest pain, weight loss and heartburn in > 90 approximately 75, 40
      - 50, approximately 60, approximately 40%, respectively [3,4]. The diagnosis is
      based on symptoms, barium swallow and manometry. A barium oesophagram typically
      shows a dilated oesophagus that tapers into a 'bird-beak' at the gastro
      oesophageal junction with lack of normal peristalsis on fluoroscopic evaluation.
      The characteristic manometric features of achalasia are abnormal LES relaxation
      and aperistalsis; additionally, the LES pressure is frequently high, but can also
      be normal. Current practice of medicine is faced with rising healthcare costs and
      limited budgets [5]. We are therefore confronted with an increasing demand to
      justify the value of our therapeutic interventions, not only from the
      risk/benefit standpoint but also from the cost perspective [6,7].

PMID- 14596656
TI  - Pharmacotherapy of dementia with Lewy bodies.
AB  - The syndrome of dementia with Lewy bodies (DLB) is characterised by the clinical
      triad of fluctuating cognitive impairment, recurrent visual hallucinations and
      spontaneous motor features of Parkinsonism. In an attempt to define DLB as a
      distinct clinical syndrome separate from Alzheimer's disease (AD) and Parkinson's
      disease (PD) with dementia, a consensus workshop in 1995 established a new set of
      diagnostic criteria. Dementia that precedes or accompanies the onset of
      spontaneous (i.e., not neuroleptic-induced) Parkinsonism is termed DLB. In
      addition, fluctuations in alertness, cognition and function and visual
      hallucinations are emphasised and included as core features of DLB. The degree to
      which an individual patient exhibits cognitive impairment, behavioural problems
      and Parkinsonian features is variable. Therefore, treatment must be
      individualised. Although there are no officially approved drugs for DLB, limited
      experience from clinical trials, as well as past experience with the treatment of
      AD and PD patients, provide some basis for making drug choices. The cholinergic
      deficit seen in DLB makes cholinesterase inhibitor drugs the mainstay of
      treatment for cognitive impairment. This class of drugs has also shown
      therapeutic benefit in reducing hallucinations and other neuropsychiatric
      symptoms of the disease. Because of their relatively greater therapeutic window,
      cholinesterase inhibitors are also used as first-line therapy for the treatment
      of psychosis in DLB. Patients with DLB are extremely sensitive to the
      extrapyramidal side effects of neuroleptic medications. Thus, only atypical
      antipsychotic agents such as quetiapine, should be considered as alternative
      treatment for psychosis. Anxiety and depression are best treated with selective
      serotonin re-uptake inhibitors, whereas REM sleep behaviour disorder may be
      treated with low dose clonazepam. Parkinsonism responds to dopaminergic agents;
      however, precipitation or aggravation of hallucinosis may occur. Levodopa is
      preferred over dopamine agonists due to its lower propensity to cause
      hallucinations and somnolence. As the diagnostic criteria for DLB become more
      refined and validated by postmortem studies, it is hoped that rigorous, well
      designed trials will be performed, aimed at alleviating the primary target
      symptoms of dementia, psychosis and Parkinsonism.

PMID- 14596657
TI  - Infantile spasms.
AB  - Infantile spasms is a catastrophic form of epilepsy found only in infants and
      young toddlers, with the peak incidence between 4 - 7 months of age. Estimated
      prevalence is 1 in 2000 - 6000 live births. There are many causes of infantile
      spasms, including tuberous sclerosis, hypoxic-ischaemic injury, congenital
      infectious diseases, inborn errors of metabolism, malformations of cortical
      development, genetic syndromes such as Aicardi's syndrome and chromosomal
      abnormalities. A small percentage of patients have idiopathic infantile spasms,
      with normal growth and development prior to the onset of infantile spasms and no
      known aetiology. Because of the poor prognosis of infantile spasms, treatment is
      usually aggressive and immediate, with the hopes of altering the natural history
      of the disease. The majority of patients with infantile spasms have a poor
      prognosis with intractable epilepsy, severe developmental delays and/or
      significant cognitive impairments. Of all patients with infantile spasms, 70 -
      90% have mental retardation. Furthermore, 20 - 50% of patients with infantile
      spasms develop Lennox-Gastaut syndrome with multiple seizure types, cognitive
      impairments and a markedly abnormal electroencephalogram, arguably one of the
      most difficult epilepsy syndromes to treat. Infantile spasms are resistant to
      most of the standard antiepileptic drugs. Adrenocorticotropin hormone (ACTH) or
      oral steroids result in a significant reduction of seizures, as well as an
      improvement in the electroencephalogram. Some studies have indicated that infants
      treated with ACTH within the first month of onset have a more favourable
      prognosis. Vigabatrin has also been shown to be effective in the treatment,
      although it is not yet FDA-approved in the US. Valproate has also been used in
      the treatment of infantile spasms, with an efficacy of approximately 25 - 40%.
      However, in the very young infant, it does carry a high risk of fatal
      hepatotoxicity. Surgical resection may be the treatment of choice for those
      infants with focal cortical dysplasia and intractable infantile spasms. Emerging
      therapeutic possibilities include topiramate, felbamate, lamotrigine, zonisamide
      and perhaps levetiracetam. With the advancements in molecular biology, genetics
      and neuroimaging, there is the hope of novel therapies in the future.

PMID- 14596658
TI  - Review of tadalafil in the treatment of erectile dysfunction.
AB  - Approximately 150 million men worldwide experience erectile dysfunction (ED)
      whereby they are unable to achieve and maintain an erection adequate for
      satisfactory sexual performance. ED has a considerable impact on quality of life.
      Tadalafil (Cialis( trade mark ), Eli Lilly & Co./ICOS) is a novel effective and
      safe phosphodiesterase type 5 inhibitor, a secondary messenger for the smooth
      muscle relaxing effects of nitric oxide, which plays a central role in the
      vasodilation of erectile tissues. It has a longer half-life than sildenafil. As
      head-to-head comparative trials are lacking, it is not clear what tadalafil
      offers over sildenafil. In terms of marketing, much is made of the 'spontaneity'
      achievable because of the (relatively) longer half-life of tadalafil.

PMID- 14596659
TI  - Alfuzosin for the management of benign prostate hyperplasia.
AB  - Alfuzosin (UroXatral, Sanofi-Synthelabo) a quinazoline derivative, has well
      documented alpha(1)-adrenoreceptor antagonist activity. These receptors are
      present in the smooth muscle located at the bladder base, proximal urethra,
      prostate and prostatic capsule as well as in vascular and nervous systems.
      Consequently, alfuzosin has the ability to reduce the tone of these areas,
      effectively decreasing bladder outlet resistance. A sustained-release formulation
      of alfuzosin is currently available in Europe and is FDA-approved in the US. The
      confirmed efficacy, proven bioavailability and good cardiovascular safety profile
      support the use of this drug for the management of lower urinary tract symptoms
      secondary to benign prostate hyperplasia (BPH). These findings have been
      confirmed in a large cohort of patients treated in general practice.
      Additionally, treatment with alfuzosin has demonstrated a favourable impact on
      quality of life of patients with BPH.

PMID- 14596660
TI  - Treatment of premenstrual dysphoric disorder with luteal phase dosing of
      sertraline.
AB  - Sertraline (Zoloft, Pfizer Inc.) is a selective serotonin re-uptake inhibitor
      (SSRI) which has been approved by the US FDA for the treatment of premenstrual
      dysphoric disorder (PMDD). PMDD is a severe form of premenstrual syndrome (PMS)
      which affects at least 5 - 8% of women of reproductive age. It is characterised
      by cyclic appearance at the late luteal phase of the menstrual cycle, and
      disappearance following the beginning of menses, with no symptoms during at least
      1 week of the cycle - usually during the mid-follicular phase. Due to the cyclic
      luteal occurrence of PMDD, luteal phase dosing of SSRIs has been suggested and
      proven effective for sertraline as well as several other SSRIs. The clinical
      response of sertraline is reported to be within several days following initiation
      of treatment. Despite repeated cyclic discontinuation, no significant
      discontinuation adverse effects have been reported. In addition to its proven
      clinical efficacy, luteal-phase dosing may offer the advantages of minimising
      adverse effects of SSRIs while reducing the personal and economic burden of
      taking a prescription medication continuously for long periods and thus
      increasing compliance.

PMID- 14596661
TI  - Levetiracetam: treatment in epilepsy.
AB  - A large number of new antiepileptic drugs (AEDs) have become available over the
      last 10 years. Results from placebo-controlled clinical trials and community
      based practice have demonstrated that levetiracetam has a broad spectrum of
      activity in suppressing seizures as add-on treatment and monotherapy and that it
      is safe and well-tolerated. Levetiracetam also has a favourable pharmacokinetic
      profile characterised by rapid and nearly complete absorption, very low potential
      for drug interactions and a prolonged pharmacodynamic effect that permits twice
      daily dosing. Although, the mechanism of action of levetiracetam is not
      completely understood, preclinical studies suggest that it may have
      antiepileptogenic and neuroprotective effects, with the potential to slow or
      arrest disease progression.

PMID- 14596662
TI  - Alosetron and irritable bowel syndrome.
AB  - Alosetron (Lotronex, GlaxoSmithKline) is a potent and selective 5-HT(3)-receptor
      antagonist approved by the FDA for the treatment of women with diarrhoea
      predominant irritable bowel syndrome (IBS) in whom conventional therapy has
      failed. Studies involving healthy volunteers and IBS patients have demonstrated a
      beneficial effect of treatment with alosetron on global IBS symptoms, abdominal
      pain and discomfort, altered bowel function as well as improvement of quality of
      life (QOL). Data from animals studies suggest the involvement of 5-HT(3)
      receptors on intrinsic primary afferent neurons in the mediation of the effect of
      alosetron on gastrointestinal motility and secretion. While definitive proof of a
      visceroanalgesic action is not available, an additional central mechanism of
      action is suggested by findings obtained in animal models, as well as from human
      brain imaging studies. Alosetron shows a greater effectiveness in women, and the
      role of genetic factors underlying inter-individual differences in the response
      to alosetron is currently under investigation. The most frequent adverse event
      associated with the use of alosetron is constipation and in some rare cases, the
      development of colonic mucosal ischaemia. In the following review, the most
      recent reported effects of alosetron on gastrointestinal motility, visceral
      sensitivity and anxiety, both in terms of preclinical and clinical data will be
      discussed. The impact of alosetron on QOL in IBS patients and the safety of
      treatment with alosetron, will also be covered.

PMID- 14596663
TI  - Amphotericin B lipid complex for the treatment of invasive fungal infections.
AB  - Amphotericin B lipid complex (ABLC; Abelcet, Enzon Pharmaceuticals) has become
      the dominant marketed lipid amphotericin B compound to emerge since the approval
      of these agents from the mid-1990s onwards. This agent is a 1:1 combination of
      amphotericin B and a lipid moiety consisting of dimyristoyl phosphatidylcholine
      and dimyrisoyl phosphatidylcholine, which exists in a ribbon-like molecular
      structure. ABLC undergoes rapid reticuloendothelial uptake from the circulation
      and achieves significantly higher tissue concentrations in the liver, spleen and
      lung compared to comparably dosed conventional amphotericin B. ABLC is approved
      by the FDA for all mycoses in amphotericin B-intolerant or -refractory infection.
      Randomised, controlled trials of amphotericin B have shown comparable efficacy in
      candidiasis and an improved outcome in invasive aspergillosis versus historical
      controls. ABLC has demonstrated a reduced incidence of nephrotoxicity and
      infusion reactions versus amphotericin B. Comparative studies against other lipid
      formulations are quite limited and have shown variable differences in infusion
      toxicity, nephrotoxicity, hepatotoxicity and clinical efficacy. Postapproval
      experience has shown substantial efficacy for less common mycotic pathogens
      including zygomycosis. The precise position of ABLC versus both other lipid
      formulations and expanding formulary of new antifungal agents is in flux. Future
      studies which examine its clinical efficacy, role in combination therapy,
      toxicity and cost-effectiveness in these complex patients are needed.

PMID- 14596664
TI  - Are implantable cardioverter-defribrillators always superior to amiodarone?
AB  - The beneficial effects of amiodarone in preventing sudden cardiac death may
      predominantly be in patients without coronary artery disease. The AMIOdarone
      Versus Implantable CardioveRTer-defibrillator trial (AMIOVIRT) compared
      amiodarone and an implantable cardioverter-defribrillator (ICD) in non-ischaemic
      dilated cardiomyopathy with non-sustained ventricular arrhythmia. The trial was
      discontinued at the first interim analysis, as the prospective rule for inability
      to demonstrate statistical significance was reached. There were 7 deaths (5
      cardiac, 2 sudden) in the amiodarone group (n = 52) and 6 (4 cardiac, 1 sudden)
      in the ICD group (n = 51). The cost of total medical care was lower in the
      amiodarone group than the ICD group. A reasonable approach may be to use the
      cheaper amiodarone initially in patients with non-ischaemic cardiomyopathy with
      non-sustained ventricular arrhythmias and when near syncope occurs, to insert an
      ICD.

PMID- 14596665
TI  - Toll-like receptor signalling pathways as key targets for mediating the anti
      inflammatory and immunosuppressive effects of glucocorticoids.
AB  - Toll-like receptors (TLRs) play crucial roles in the induction of innate immune
      responses by recognising pathogen-associated molecular patterns. The engagement
      of TLRs by pathogens results in induction of co-stimulatory molecules that
      facilitate a specific immune response and also in the induction of pro
      inflammatory proteins that will promote the elimination of pathogens from the
      body. TLRs employ many of the same signalling components as the type I
      interleukin (IL)-1 receptor (IL-1R). This is hardly surprising since the
      intracellular regions of TLRs and the IL-1R share a conserved Toll/IL-1R homology
      domain (TIR) that allows the receptors to recruit the intracellular TIR
      containing adaptor protein Myd88. The latter then activates IL-1R-associated
      kinases that in turn recruit well-characterised downstream effectors culminating
      in activation of MAP kinases and transcription factors such as NFkappaB and AP-1.
      Since glucocorticoids are known to target the latter transcription factors and
      the MAP kinase cascades, this commentary highlights the likely crucial importance
      of Toll-like receptor signalling pathways as key targets for mediating the anti
      inflammatory and immunosuppressive effects of steroids.

PMID- 14596666
TI  - Transgenic mice over-expressing galanin exhibit pituitary adenomas and increased
      secretion of galanin, prolactin and growth hormone.
AB  - Galanin is a biologically active 29 amino acid peptide, widely distributed in the
      central and peripheral nervous system, and most abundantly in the hypothalamus
      where it may serve in the regulation of anterior pituitary hormones. We herein
      report that mice carrying the rat preprogalanin cDNA specifically targeted to the
      somatomammotroph cell lineage, under the control of the rat GH promoter, over
      express and over-secrete galanin. Galanin peptide is localised within the GH and
      prolactin secretory granules. GH and prolactin release is increased as well,
      predominantly in males, while older transgenic animals develop pituitary
      hyperplasia and adenoma. In both male and female transgenic mice there is a
      significant increase in serum galanin (P<0.00003 and P<0.001 respectively) and
      prolactin (P<0.002 and P<0.05 respectively) levels, while only in male transgenic
      mice is there a significant increase in the serum levels of GH. Furthermore, in
      male transgenic mice serum prolactin levels are significantly correlated with the
      serum galanin levels (P<0.03). We conclude that galanin plays a key role in the
      process of pituitary hyperplasia, acting as a growth factor to promote pituitary
      cell proliferation, and participates in pituitary adenoma formation not
      necessarily dependent on oestrogens. Targeted over-expression and over-secretion
      of galanin in the somatomammotroph cell lineage stimulates predominantly
      hyperprolactinaemia in an oestrogen-independent manner.

PMID- 14596667
TI  - N-methyl-D-aspartate receptor activity and estradiol: separate regulation of cell
      proliferation in the dentate gyrus of adult female meadow vole.
AB  - We have previously found that estradiol increases (within 4 h) but then decreases
      (within 48 h) cell proliferation in the dentate gyrus of adult female
      ovariectomized (OVX) rats and of intact meadow voles and that estradiol partially
      stimulates adrenal activity to suppress cell proliferation in rats. Estradiol
      enhances N-methyl-D-aspartate receptor (NMDAr) activity and NMDAr activation
      suppresses cell proliferation in the adult rodent dentate gyrus. Therefore, we
      tested whether estradiol alters cell proliferation in the dentate gyrus of adult
      OVX female meadow voles by stimulating NMDAr activity. In experiment 1, OVX
      females were injected with estradiol (10 micro g) or oil and then with NMDA (30
      mg/kg) or vehicle 3 h later and bromodeoxyuridine 4 h later (BrdU; 50 mg/kg).
      Voles were perfused 1 h after BrdU injection. Relative to oil vehicle, estradiol
      increased (P</=0.001) and NMDA decreased (P</=0.006) labeled cell number.
      Coadministration of estradiol/NMDA increased labeled cell numbers relative to
      NMDA alone (P</=0.03), suggesting that within 4 h estradiol does not influence
      the effect of NMDA receptors on cell proliferation. In experiment 2, OVX females
      were injected with either estradiol or oil and then with either MK-801 (1 mg/kg)
      or vehicle 47 h later and BrdU 48 h later. The animals were perfused 1 h after
      BrdU was injected. Relative to oil-treated voles, estradiol-treated voles had
      fewer (P<0.006) and MK-801-treated voles had more labeled cells (P</=0.0001) in
      the dentate gyrus. However, estradiol did not appear to stimulate NMDA receptors
      to suppress cell proliferation because estradiol (48 h)/MK-801-treated voles had
      fewer BrdU-labeled cells than oil (48 h)/MK-801-treated voles (P</=0.06). The
      results show that estradiol time-dependently influences cell proliferation but
      that estradiol does not stimulate NMDAr activity to influence cell proliferation
      in the dentate gyrus of adult voles.

PMID- 14596668
TI  - A role for acidophilic granulocytes in the testis of the gilthead seabream
      (Sparus aurata L., Teleostei).
AB  - In mammals, a complex interaction between the immune and the reproductive systems
      has been described, in which testicular immune cells produce cytokines and growth
      factors which modulate gonad functions, while specific gonad cells influence the
      immune response in this organ. In this study we describe the presence of
      acidophilic granulocytes in the testis of the hermaphrodite teleost fish gilthead
      seabream (Sparus aurata L.) by using a specific monoclonal antibody. During the
      post-spawning stage of the testis, this cell type appears in the germinal
      compartment, accumulates interleukin (IL)-1beta and does not seem to be involved
      in the phagocytosis of degenerating cells. Moreover, in vitro, 11
      ketotestosterone and 17beta-oestradiol, the principal fish sexual steroids,
      regulate the respiratory burst activity of acidophilic granulocytes obtained from
      the head-kidney (the bone marrow equivalent in fish) and the intracellular
      accumulation of IL-1beta by these cells. It is likely, therefore, that IL-1beta
      produced by testicular acidophilic granulocytes regulates important functions of
      the testis in fish.

PMID- 14596669
TI  - Isolation and characterization of Leydig cells from adult bonnet monkeys (Macaca
      radiata): evidence for low steroidogenic capacity in monkey Leydig cells in
      contrast to rat Leydig cells.
AB  - Most of the available information on Leydig cells has been obtained using a
      rodent model system. With an objective to extend the observations made with rat
      Leydig cells (RLCs) to primates, a method has been developed to isolate Leydig
      cells from monkey (Macaca radiata) testis. Enzymatic dissociation of monkey
      testis followed by Percoll-gradient fractionation of the interstitial cells
      resulted in the recovery of Leydig cells at densities corresponding to 1.064
      1.070 g/ml. Purified (90-94%) monkey Leydig cells (MLCs) stained positive for the
      Leydig cell marker 3beta-hydroxysteroid dehydrogenase. The cells responded to in
      vitro addition of human chorionic gonadotropin (hCG) and produced testosterone.
      Comparison of the in vitro testosterone-producing ability of MLCs with RLCs
      revealed that MLCs have much less steroidogenic capacity compared with the RLCs.
      Analysis revealed that limitation in substrate availability to mitochondrial
      P(450) side chain cleavage enzyme and low mitochondrial and smooth endoplasmic
      reticulum content in MLCs could be the possible reasons for the low steroidogenic
      capacity of the MLCs.

PMID- 14596670
TI  - Gonadal protection from radiation by GnRH antagonist or recombinant human FSH: a
      controlled trial in a male nonhuman primate (Macaca fascicularis).
AB  - Chemotherapy and radiation often damage spermatogenesis irreversibly in
      oncological patients and various approaches to gonadal protection have been
      tested with equivocal results. In rats, hormonal protection of spermatogenesis
      can be achieved by blocking gonadotropin secretion. However, whether the same
      mechanisms can effect gonadal protection in primates remains questionable. To
      clarify this Issue we conducted a placebo-controlled trial in a preclinical
      animal model using macaques (Macaca fascicularis). Twenty adult male monkeys
      (five in each group) were randomized to receive either recombinant human FSH,
      GnRH antagonist or saline injections (two groups) for 36 days. On day 29 all
      groups except one saline-treated control group were exposed to a single
      testicular irradiation of 4 Gy. Every 2 weeks before, during and after the
      treatment, ejaculates, body weight, testicular Volume and hormones were analyzed
      until day 539. In addition, repeated testicular biopsies were performed.
      Testicular Volume and inhibin B decreased significantly in all irradiated groups
      compared with baseline and with the non-irradiated control group, followed by a
      gradual recovery of these parameters, which was, especially at the earlier time
      points, significantly better in the FSH-treated group compared with both other
      irradiated groups. Irradiation caused a drastic decrease of sperm parameters in
      all groups, followed by a partial recovery of sperm parameters, which was
      significantly slower in the early phases of recovery in the GnRH antagonist group
      compared with the vehicle group. Testicular histology showed a significant
      depletion on study day 261 in all irradiated animals. In conclusion, in clear
      contrast to rodent studies, GnRH antagonist treatment did not provide gonadal
      protection in this primate model. FSH treatment resulted in slightly better
      recovery of spermatogenesis, which appears to be of no or only little clinical
      relevance.

PMID- 14596671
TI  - Relationship between FoxO1 protein levels and follicular development, atresia,
      and luteinization in the rat ovary.
AB  - FoxO1 is a transcription factor implicated in a growing number of physiological
      processes, including apoptosis, cell cycle progression, and insulin signaling.
      Recent findings indicate that FSH and growth factors influence ovarian functions
      in part through regulation of FoxO1. The present study utilized
      immunohistochemical analysis to determine the ovarian localization and regulation
      of FoxO1 protein levels in neonatal rats, immature rats during gonadotropin
      induced follicular development, ovulation, and luteinization, and in
      spontaneously developing ovarian cysts of aging rats. In postnatal rats, FoxO1
      immunoreactivity was very faint in ovaries of 5- and 10-day-old females. In
      contrast, strong immunoreactivity was observed in granulosa cells of larger
      developing follicles at 25 days of age. To stimulate follicle development,
      immature female rats received equine chorionic gonadotropin (eCG) followed 52 h
      later by an ovulatory dose of human chorionic gonadotropin (hCG). Prior to
      gonadotropin treatment, moderate FoxO1 immunoreactivity was observed in granulosa
      cells of small follicles. Subsequently, treatment with eCG markedly decreased
      FoxO1 protein levels in granulosa cells of healthy antral and preovulatory
      follicles. Interestingly, FoxO1 staining was observed in cumulus and antral, but
      not mural granulosa cells of preovulatory follicles. Induction of ovulation and
      luteinization with hCG further decreased ovarian FoxO1 levels, with no staining
      evident in corpora lutea. At all time points, the most intensive FoxO1 staining
      was observed in granulosa cells of atretic follicles, with predominantly nuclear
      localization. Similarly, while FoxO1 levels were low in granulosa cells of
      preovulatory follicles in proestrous rats, FoxO1 staining was intense in
      granulosa cells of spontaneously developing cystic follicles in aged, acyclic
      females. Together, these findings indicate that FoxO1 is expressed in a
      regulated, cell-specific manner during ovarian follicular development, atresia
      and luteinization, suggesting roles in these physiological processes.

PMID- 14596672
TI  - Thyroid hormone modulation of brain in vivo tyrosine hydroxylase activity and
      kinetics in the female catfish Heteropneustes fossilis.
AB  - In the female catfish Heteropneustes fossilis, administration of thyroxine
      (T(4))(,) 1 micro g/g body weight, i.p., in both gonadal resting and preparatory
      phases for 7, 14 and 21 days caused hyperthyroidism, as evidenced from a duration
      dependent significant increase in serum triiodothyronine (T(3)), and of tyrosine
      hydroxylase (TH) activity in telencephalon, hypothalamus-pituitary and medulla
      oblongata (Newman-Keuls' test; P<0.05). Hypothyroidism induced by adding 0.03%
      thiourea to aquarium water holding the catfish for 7, 14 and 21 days decreased
      serum T(3) levels in a duration-dependent manner (Newman-Keuls' test; P<0.05) and
      inhibited TH activity in the brain regions. T(4) replacement in 21day thiourea
      treated fish restored and even elevated significantly serum T(3) levels as well
      as brain TH activity in a duration-dependent manner. In general, the changes in
      enzyme activity were higher in the forebrain regions than medulla oblongata and
      in the resting phase than preparatory phase. Kinetic studies by Lineweaver-Burk
      plots showed that the stimulatory effect following T(4) administration and T(4)
      replacement on TH activity was due to increased affinity of the enzyme for its
      cofactor (6,7-dimethyl-2-amino-4-hydroxy-5,6,7,8-tetrahydropteridine), as evident
      from a significant decrease in apparent Michaelis-Menten constant (K(m)) and an
      increase in apparent velocity maximum (V(max)). The TH inhibition due to the
      thiourea treatment can be related to decreased affinity of the enzyme for its
      cofactor, as evident from a significant increase in apparent K(m) value and a
      significant decrease in V(max). These data clearly show that circulating levels
      of T(4)/T(3) modulate brain TH activity by altering the kinetic properties of the
      enzyme, which, in turn, influence catecholaminergic activity and dependent
      functions.

PMID- 14596673
TI  - Triiodothyronine affects the alternative splicing of thyroid hormone receptor
      alpha mRNA.
AB  - The c-erbAalpha gene encodes two thyroid hormone receptors, TRalpha1 and
      TRalpha2, that arise from alternative splicing of the TRalpha pre-mRNA. TRalpha2
      is not able to bind triiodothyronine (T(3)) and acts as a weak antagonist of TRs.
      It has been suggested that the balance of TRalpha1 to TRalpha2 is important in
      maintaining homeostasis. Here, we study the effect of thyroid hormone on the
      splicing of TRalpha under various conditions in HepG2 cells. First, T(3) was
      added to HepG2 cells that endogenously express TRalpha. This resulted in a
      decrease in the TRalpha1:TRalpha2 mRNA ratio after the addition of 10(-)(8 )M or
      10(-)(7 )M T(3). Then, HepG2 cells were incubated with sera from hypothyroid or
      hyperthyroid patients. Sera from hyperthyroid patients (n=6) decreased the
      TRalpha1:TRalpha2 ratio compared with HepG2 cells incubated with sera from
      euthyroid patients (n=8). Sera from hypothyroid patients (n=6) had no effect on
      the TRalpha1:TRalpha2 ratio but supplementation with T(3) caused a decrease in
      the ratio. Finally, we tested sera from patients with nonthyroidal illness (NTI;
      n=17) which showed no effect on TRalpha splicing when compared with controls.
      Free thyroxine levels in sera from hypo-, eu-, and hyperthyroid patients, but not
      that of NTI patients, were negatively correlated (P<0.01) to the
      TRalpha1:TRalpha2 ratio. We next studied the expression of the splicing factors
      hnRNP A1 and ASF/SF2 (SF2) in relation to the splicing of the TRalpha gene. In
      HepG2 cells incubated with NTI sera a negative relationship was found between the
      ratio of hnRNP A1:SF2 and the TRalpha1:TRalpha2 ratio. A high hnRNP A1:SF2 ratio
      is associated with the use of the distal 5'-splice site. The splicing direction
      should then change towards TRalpha2, which is indeed the case. Rev-ErbA, which is
      partly complementary to TRalpha2 and could therefore interfere in the splicing
      process, did not relate to the TRalpha1:TRalpha2 ratio. In conclusion, high T(3)
      levels induce a low TRalpha1:TRalpha2 ratio which could protect the cell from
      excessive T(3)-induced gene expression. In vivo, this might be a mechanism to
      keep tIssues relatively euthyroid during high serum T(3) levels.

PMID- 14596674
TI  - Expression of VGF mRNA in developing neuroendocrine and endocrine tissues.
AB  - Analysis of knockout mice suggests that the neurotropin-inducible secreted
      polypeptide VGF (non-acronymic) plays an important role in the regulation of
      energy balance. VGF is synthesized by neurons in the central and peripheral
      nervous systems (CNS, PNS), as well as in the adult pituitary, adrenal medulla,
      endocrine cells of the stomach and pancreatic beta cells. Thus VGF, like
      cholecystokinin, leptin, ghrelin and other peptide hormones that have been shown
      to regulate feeding and energy expenditure, is synthesized in both the gut and
      the brain. Although detailed developmental studies of VGF localization in the CNS
      and PNS have been completed, little is known about the ontogeny of VGF expression
      in endocrine and neuroendocrine tIssues. Here, we report that VGF mRNA is
      detectable as early as embryonic day 15.5 in the developing rat gastrointestinal
      and esophageal lumen, pancreas, adrenal, and pituitary, and we further
      demonstrate that VGF mRNA is synthesized in the gravid rat uterus, together
      supporting possible functional roles for this polypeptide outside the nervous
      system and in the enteric plexus.

PMID- 14596675
TI  - Endocrine responses to the oral ingestion of a physiological dose of essential
      amino acids in humans.
AB  - The response of insulin, human growth hormone (hGH), cortisol, leptin and
      ghrelin, in addition to various metabolic parameters, was measured at 10 minute
      intervals following the oral ingestion of a standardised physiological dose of
      essential amino acids (AA). Twenty-eight healthy male, fasted volunteers (aged 18
      40 yrs, BMI 18.0-24.5 kg/m(2)) took part in the study; 13 volunteers in the AA
      group, nine subjects in an iso-caloric control group, and a further six subjects
      served as fasting controls. Twenty minutes after ingestion, insulin reached peak
      concentrations that were up to 500% higher than basal values (P<0.0001). The AA
      group and iso-caloric control group showed a similar insulin response. AA
      ingestion led to an increase in hGH secretion with maximum concentrations being
      2100+/-1013% higher than the basal values (P<0.0001). In contrast, no changes in
      hGH concentrations were observed in the iso-caloric controls; in the fasting
      controls only a slight increase in hGH was found towards the end of the fasting
      period. While cortisol decreased significantly (P<0.01) during the study in the
      AA group, neither control group showed a significant change in this parameter.
      Changes in leptin levels remained insignificant in all three groups, whereas
      ghrelin showed a different profile in each of the three groups, i.e. a continuous
      rise towards the end of the study period (P<0.001) in the AA group, a less
      significant effect for the fasting group, and no effect at all in the iso-caloric
      control group. There was no significant correlation between the concentrations or
      the area under curve of the hormones measured in any of the groups. The endocrine
      data provided in this study indicate that a single bolus of essential AA in
      fasted individuals is associated with both anabolic and catabolic hormonal
      responses.

PMID- 14596676
TI  - The postnatal growth of the beta-cell mass in pigs.
AB  - Studies of the postnatal growth of the beta-cell mass in rats have revealed some
      unexpected and apparently paradoxical results, the most prominent being a beta
      cell mass plateau in the early phase of life. We have studied the postnatal
      growth of the beta-cell mass in the domestic pig to investigate its development
      in a larger mammal. The pancreases from a total of 86 male pigs from 5 to 100
      days of age were studied. The beta-cell mass increased linearly from day 5 to day
      40, reached a plateau from day 40 to day 60, and then increased further into
      adulthood. The relative beta-cell mass (beta-cell mass per body mass) was
      increased in the early postnatal period but reached a constant level from day 60,
      after which there was a linear relationship between the beta-cell mass and the
      body mass. There were high rates of both beta-cell apoptosis and mitosis at 50
      and 60 days of age, while the Volume-weighted mean islet Volume increased from
      birth and reached a plateau at approximately 60 days of age. A beta-cell mass
      plateau early in life accompanied by a wave of beta-cell apoptosis coinciding
      with the relative beta-cell mass decreasing to reach a constant level, and a
      linear relationship between the beta-cell mass and the body mass in later life is
      exactly what has previously been reported in rats. The coincidence of these
      events in both rats and pigs, although occurring at different ages in the two
      species, suggests a causal relationship as previously suggested in a proposed
      explanatory model for postnatal beta-cell growth.

PMID- 14596678
TI  - IGF-I but not insulin inhibits apoptosis at a low concentration in vascular
      smooth muscle cells.
AB  - Apoptosis of vascular smooth muscle cells (VSMCs) is of importance in the
      development of diabetic angiopathy. Our aim was to evaluate the effect of insulin
      and IGF-I on apoptosis in VSMCs. Rat aortic VSMCs were used and apoptosis was
      induced by serum starvation. As apoptotic markers we measured caspase-3 activity,
      histone-associated DNA fragments by ELISA and nuclear morphology by DAPI (4',6
      diamidino-2-phenylindole) staining. Phosphorylation of IGF-I receptors was
      evaluated by Western blot. Serum starvation had increased caspase-3 activity even
      after 3 h. The highest activity was found after 3-12 h. IGF-I 10(-9 )M inhibited
      serum starvation-induced caspase-3 activity with a maximal effect after 12 h.
      When studied after starvation for 12 h, significant inhibitory effects on caspase
      3 were found at IGF-I concentrations of 10(-8)-10(-7) M (P<0.01) and at an
      insulin concentration of 10(-6 )M (P<0.01). DNA fragmentation was detected by
      ELISA after 24 h and chromatin condensation and nuclear fragmentation by DAPI
      staining after 24 and 48 h respectively. IGF-I dose-dependently reduced apoptosis
      evaluated by ELISA, reaching a maximal effect at 10(-9) M. Insulin reduced
      apoptosis but the effect was weaker and a higher concentration was needed. IGF-I
      (10(-8 )M) and insulin at a very high concentration (10(-6) M) phosphorylated IGF
      I receptors. Taken together, IGF-I and insulin have antiapoptotic effects on
      VSMCs but the effect of insulin is only found at high unphysiological
      concentration.

PMID- 14596679
TI  - Prolonged low-dose dexamethasone treatment, in early gestation, does not alter
      blood pressure or renal function in adult sheep.
AB  - Low-dose dexamethasone treatment is used in pregnancies where the fetus is
      suspected to be at risk of congenital adrenal hyperplasia (CAH). In order to see
      if such treatment had long-term effects, pregnant ewes were treated with
      dexamethasone (20 micro g/kg maternal body weight) or saline from 25 to 45 days
      of gestation and blood pressure and renal function studied in offspring at 2
      Years of age. There were 11 animals from dexamethasone treatment (six females and
      five males) and nine lambs from saline treatment (five females and four males).
      We aimed to study blood pressure and heart rate in the adult animals of both
      genders, and renal function only in the adult female animals. In both females and
      males, blood pressure and heart rate were similar between the two groups of
      animals. The excretion rates of sodium and potassium were similar between the two
      groups of animals. In addition, glomerular filtration rate was not different
      between the two groups of animals (112+/-11 ml/kg per h (S.E.M.) in saline
      treated females vs 112+/-10 ml/kg per h in dexamethasone-treated females). There
      were no differences in body weight or weights of the kidney and heart between the
      treatments in both females and males. In conclusion, these results are reassuring
      for patients similarly exposed to prenatal dexamethasone treatment for CAH, as in
      our animal model no evidence of altered renal function or predisposition to adult
      hypertension was found.

PMID- 14596677
TI  - Insulin down-regulates insulin receptor substrate-2 expression through the
      phosphatidylinositol 3-kinase/Akt pathway.
AB  - Insulin receptor substrate (IRS)-1 and IRS-2 are the major substrates that
      mediate insulin action. Insulin itself regulates the expression of the IRS
      protein in the liver, but the underlying mechanisms of IRS-1 and IRS-2 regulation
      are not fully understood. Here we report that insulin suppressed the expression
      of both IRS-1 and IRS-2 proteins in Fao hepatoma cells. The decrease in IRS-1
      protein occurred via proteasomal degradation without any change in IRS-1 mRNA,
      whereas the insulin-induced suppression of IRS-2 protein was associated with a
      parallel decrease in IRS-2 mRNA without changing IRS-2 mRNA half-life. The
      insulin-induced suppression of IRS-2 mRNA and protein was blocked by the
      phosphatidylinositol (PI) 3-kinase inhibitor, LY294002, but not by the MAP kinase
      ERK kinase (MEK) inhibitor, PD098059. Inhibition of Akt by overexpression of
      dominant-negative Akt also caused complete attenuation of the insulin-induced
      decrease in IRS-2 protein and partial attenuation of its mRNA down-regulation.
      Some nuclear proteins bound to the insulin response element (IRE) sequence on the
      IRS-2 gene in an insulin-dependent manner in vitro, and the binding was also
      blocked by the PI 3-kinase inhibitor. Reporter gene assay showed that insulin
      suppressed the activity of both human and rat IRS-2 gene promoters through the
      IRE in a PI 3-kinase-dependent manner. Our results indicate that insulin
      regulates IRS-1 and IRS-2 through different mechanisms and that insulin represses
      IRS-2 gene expression via a PI 3-kinase/Akt pathway.

PMID- 14596680
TI  - Cloning of Octopus cephalotocin receptor, a member of the oxytocin/vasopressin
      superfamily.
AB  - We reported that the common octopus, Octopus vulgaris, in common with
      vertebrates, possesses two members of the oxytocin/vasopressin superfamily:
      octopressin (OP) and cephalotocin (CT). This was the first observation of its
      kind in invertebrates. As OP and CT have different biological activities, the
      presence of specific receptors has been proposed. We cloned the cDNA of an orphan
      receptor from Octopus brain and found it to encode a polypeptide of 397 amino
      acids that displays sequences characteristic of G-protein coupled receptors. The
      orphan receptor showed high homology to receptors of the oxytocin/vasopressin
      superfamily and seemed to conserve the agonist-binding pocket common to the
      oxytocin and vasopressin receptors. Xenopus oocytes that express the orphan
      receptor responded to the application of CT by an induction of membrane Cl(-)
      currents coupled to the inositol phosphate/Ca(2+) pathway. OP and the other
      members of the oxytocin/vasopressin superfamily did not activate this receptor.
      HPLC fractionation of the Octopus brain extract combined with an oocyte assay
      yielded a single substance that was identical to CT. On the basis of these
      results, we conclude that the cloned receptor is the CT receptor (CTR).
      Expression of CTR mRNA in Octopus was detected in the central and the peripheral
      nervous systems, the pancreas, the oviduct and the ovary. This receptor may
      mediate physiological functions of CT in Octopus such as neurotransmission,
      reproduction and metabolism.

PMID- 14596681
TI  - Steroidogenic factor-1 enhances basal and forskolin-stimulated transcription of
      the human glycoprotein hormone alpha-subunit gene in GH3 cells.
AB  - Steroidogenic factor-1 (SF-1) is a key regulator of endocrine development, and
      mediates expression of gonadotrophin-specific genes in the pituitary. Basal and
      hormone stimulated transcription of the human glycoprotein hormone alpha-subunit
      gene (alphaGSU) in gonadotrophs involves SF-1 and its cognate binding site, the
      gonadotroph-specific element (GSE). In this study, we demonstrate that SF-1
      significantly enhances basal and forskolin-stimulated transcription of the human
      alphaGSU promoter in GH(3) cells. Mutation of the GSE abolished the SF-1-mediated
      transactivation of basal alphaGSU promoter activity, and significantly attenuated
      the forskolin effect by 50%. Mutation of the Ser203 residue in SF-1 to Ala
      blocked basal transactivation of alphaGSU promoter activity, and halved the
      forskolin effect. These data collectively reveal a direct role for SF-1 and the
      GSE in mediating basal and forskolin-stimulated transcription of the human
      alphaGSU promoter in GH(3) cells. The phosphorylation site at Ser203 appears to
      be required for these effects.

PMID- 14596682
TI  - Is quality of life measurement likely to be a proxy for health needs assessment
      in patients with coronary artery disease?
AB  - BACKGROUND: The identification of patients' health needs is pivotal in optimising
      the quality of health care, increasing patient satisfaction and directing
      resource allocation. Health needs are complex and not so easily evaluated as
      health-related quality of life (HRQL), which is becoming increasingly accepted as
      a means of providing a more global, patient-orientated assessment of the outcome
      of health care interventions than the simple medical model. The potential of HRQL
      as a surrogate measure of healthcare needs has not been evaluated. OBJECTIVES AND
      METHOD: A generic (Short Form-12; SF-12) and a disease-specific questionnaire
      (Seattle Angina Questionnaire; SAQ) were tested for their potential to predict
      health needs in patients with acute coronary disease. A wide range of healthcare
      needs were determined using a questionnaire specifically developed for this
      purpose. RESULTS: With the exception of information needs, healthcare needs were
      highly correlated with health-related quality of life. Patients with limited
      enjoyment of personal interests, weak financial situation, greater dependency on
      others to access health services, and dissatisfaction with accommodation reported
      poorer HRQL (SF-12: p < 0.001; SAQ: p < 0.01). Difficulties with mobility, aids
      to daily living and activities requiring assistance from someone else were
      strongly associated with both generic and disease-specific questionnaires (SF-12:
      r = 0.46-0.55, p < 0.01; SAQ: r = 0.53-0.65, p < 0.001). Variables relating to
      quality of care and health services were more highly correlated with SAQ
      components (r = 0.33-0.59) than with SF-12 (r = 0.07-0.33). Overall, the disease
      specific Seattle Angina Questionnaire was superior to the generic Short Form-12
      in detecting healthcare needs in patients with coronary disease. Receiver
      operator curves supported the sensitivity of HRQL tools in detecting health
      needs. CONCLUSION: Healthcare needs are complex and developing suitable
      questionnaires to measure these is difficult and time-consuming. Without a
      satisfactory means of measuring these needs, the extent to which disease impacts
      on health will continue to be underestimated. Further investigation on larger
      populations is warranted but HRQL tools appear to be a reasonable proxy for
      healthcare needs, as they identify the majority of needs in patients with
      coronary disease, an observation not previously reported in this patient group.

PMID- 14596683
TI  - Enoximone echocardiography: a novel test to evaluate left ventricular contractile
      reserve in patients with heart failure on chronic beta-blocker therapy.
AB  - BACKGROUND: It has been suggested that an extensive contractile reserve
      identified recognised by means of dobutamine stress echocardiography may predict
      a better prognosis in patients with severe left ventricular dysfunction at rest.
      However, the clinical use of dobutamine stress echocardiography may be limited in
      patients with chronic heart failure by the substantial proportion of such
      patients treated with beta-blockers, since the inotropic response to adrenergic
      stimulation is known to be attenuated in patients receiving beta-adrenoceptor
      blockers. Enoximone is a positive inotropic agent that inhibits cyclic adenosine
      monophosphate-specific phosphosdiesterase. We therefore tested the hypothesis
      that enoximone may be an alternative to dobutamine in evaluating left ventricular
      contractile reserve in patients with systolic dysfunction on chronic beta-blocker
      therapy. METHODS: We studied 26 patients (21 males and five females) with a mean
      age of 58 PlusMinus; 10 years: 11 were not receiving beta-blockers (noBB group);
      15 were receiving carvedilol at a mean dose of 34 mg/day (BB group). Dobutamine
      was infused at doses of 5 and 10 micrograms/kg/min, and enoximone at a dose of
      1.5 mg/kg. RESULTS: The ejection fraction in the noBB group increased by 9% with
      dobutamine and 8.73% with enoximone (p = 0.86); in the BB group, it increased by
      6% with dobutamine and 8.94% with enoximone (p = 0.03). Regional peak systolic
      velocities were evaluated by means of tissue Doppler imaging in four basal and
      four medium level segments. In the noBB group, they increased more with
      dobutamine than with enoximone in three of the eight segments; no significant
      differences were found in the BB group. Dobutamine induced non-sustained
      ventricular tachycardia in three patients and supraventricular tachycardia in
      one, whereas enoximone did not induce any repetitive arrhythmias. CONCLUSIONS:
      Enoximone might be preferable to low-dose dobutamine for evaluating left
      ventricular contractile reserve in chronically beta-blocked heart failure
      patients as it is slightly more potent and has a better safety profile.

PMID- 14596684
TI  - Inter-rater reliability of nursing home quality indicators in the U.S.
AB  - BACKGROUND: In the US, Quality Indicators (QI's) profiling and comparing the
      performance of hospitals, health plans, nursing homes and physicians are
      routinely published for consumer review. We report the results of the largest
      study of inter-rater reliability done on nursing home assessments which generate
      the data used to derive publicly reported nursing home quality indicators.
      METHODS: We sampled nursing homes in 6 states, selecting up to 30 residents per
      facility who were observed and assessed by research nurses on 100 clinical
      assessment elements contained in the Minimum Data Set (MDS) and compared these
      with the most recent assessment in the record done by facility nurses. Kappa
      statistics were generated for all data items and derived for 22 QI's over the
      entire sample and for each facility. Finally, facilities with many QI's with poor
      Kappa levels were compared to those with many QI's with excellent Kappa levels on
      selected characteristics. RESULTS: A total of 462 facilities in 6 states were
      approached and 219 agreed to participate, yielding a response rate of 47.4%. A
      total of 5758 residents were included in the inter-rater reliability analyses,
      around 27.5 per facility. Patients resembled the traditional nursing home
      resident, only 43.9% were continent of urine and only 25.2% were rated as likely
      to be discharged within the next 30 days. Results of resident level comparative
      analyses reveal high inter-rater reliability levels (most items >.75). Using the
      research nurses as the "gold standard", we compared composite quality indicators
      based on their ratings with those based on facility nurses. All but two QI's have
      adequate Kappa levels and 4 QI's have average Kappa values in excess of.80. We
      found that 16% of participating facilities performed poorly (Kappa <.4) on more
      than 6 of the 22 QI's while 18% of facilities performed well (Kappa >.75) on 12
      or more QI's. No facility characteristics were related to reliability of the data
      on which Qis are based. CONCLUSION: While a few QI's being used for public
      reporting have limited reliability as measured in US nursing homes today, the
      vast majority of QI's are measured reliably across the majority of nursing
      facilities. Although information about the average facility is reliable, how the
      public can identify those facilities whose data can be trusted and whose cannot
      remains a challenge.

PMID- 14596685
TI  - Sugar recognition by human galactokinase.
AB  - BACKGROUND: Galactokinase catalyses the first committed step of galactose
      catabolism in which the sugar is phosphorylated at the expense of MgATP. Recent
      structural studies suggest that the enzyme makes several contacts with galactose-
      five side chain and two main chain hydrogen bonds. Furthermore, it has been
      suggested that inhibition of galactokinase may help sufferers of the genetic
      disease classical galactosemia which is caused by defects in another enzyme of
      the pathway galactose-1-phosphate uridyl transferase. Galactokinases from
      different sources have a range of substrate specificities and a diversity of
      kinetic mechanisms. Therefore only studies on the human enzyme are likely to be
      of value in the design of therapeutically useful inhibitors. RESULTS: Using
      recombinant human galactokinase expressed in and purified from E. coli we have
      investigated the sugar specificity of the enzyme and the kinetic consequences of
      mutating residues in the sugar-binding site in order to improve our understanding
      of substrate recognition by this enzyme. D-galactose and 2-deoxy-D-galactose are
      substrates for the enzyme, but N-acetyl-D-galactosamine, L-arabinose, D-fucose
      and D-glucose are all not phosphorylated. Mutation of glutamate-43 (which forms a
      hydrogen bond to the hydroxyl group attached to carbon 6 of galactose) to alanine
      results in only minor changes in the kinetic parameters of the enzyme. Mutation
      of this residue to glycine causes a ten-fold drop in the turnover number. In
      contrast, mutation of histidine 44 to either alanine or isoleucine results in
      insoluble protein following expression in E. coli. Alteration of the residue that
      makes hydrogen bonds to the hydroxyl attached to carbons 3 and 4 (aspartate 46)
      results in an enzyme that although soluble is essentially inactive. CONCLUSIONS:
      The enzyme is tolerant to small changes at position 2 of the sugar ring, but not
      at positions 4 and 6. The results from site directed mutagenesis could not have
      been predicted from the crystal structure alone and needed to be determined
      experimentally.

PMID- 14596687
TI  - Elderly patients with advanced non-small-cell lung cancer.

PMID- 14596686
TI  - Mitochondrial activities in human cultured skin fibroblasts contaminated by
      Mycoplasma hyorhinis.
AB  - BACKGROUND: Mycoplasma contaminations are a recurrent problem in the use of
      cultured cells, including human cells, especially as it has been shown to impede
      cell cycle, triggering cell death under various conditions. More specific
      consequences on cell metabolism are poorly known. RESULTS: Here we report the
      lack of significant consequence of a heavy contamination by the frequently
      encountered mycoplasma strain, M. hyorhinis, on the determination of respiratory
      chain activities, but the potential interference when assaying citrate synthase.
      Contamination by M. hyorhinis was detected by fluorescent imaging and further
      quantified by the determination of the mycoplasma-specific phosphate
      acetyltransferase activity. Noticeably, this latter activity was not found
      equally distributed in various mycoplasma types, being exceptionally high in M.
      hyorhinis. CONCLUSION: While we observed a trend for respiration reduction in
      heavily contaminated cells, no significant and specific targeting of any
      respiratory chain components could be identified. This suggested a potential
      interference with cell metabolism rather than direct interaction with respiratory
      chain components.

PMID- 14596689
TI  - Epidermal growth factor receptor inhibitors, gefitinib and erlotinib (Tarceva ,
      OSI-774), in the treatment of bronchioloalveolar carcinoma.

PMID- 14596690
TI  - Benefit of active treatment in non-small-cell lung cancer in elderly patients and
      patients with poor performance status.

PMID- 14596691
TI  - Anemia in lung cancer: clinical impact and management.
AB  - Anemia has a high prevalence in patients with lung cancer. Its frequency and
      severity depend on tumor stage, duration of disease, and previous and current
      treatment. Anemia affects the health-related quality of life and impacts
      prognosis and outcome of therapy. Despite this clinical relevance, anemia is
      often underrecognized and undertreated. Treatment options include the
      administration of hematopoietic growth factors and red blood cell transfusions.
      Blood transfusions result in rapid but often transient improvement of anemia.
      Administration of epoetin or darbepoetin alfa increases hemoglobin levels,
      decreases blood transfusions, and improves quality of life in patients with lung
      cancer. Trials determining the exact association of anemia with response to
      chemotherapy/radiation therapy and survival are ongoing. Oncologists must be
      aware of the clinical relevance of anemia and offer adequate treatment options to
      their patients.

PMID- 14596692
TI  - Chemotherapy for malignant pleural mesothelioma.
AB  - Malignant pleural mesothelioma is an aggressive malignancy with no known single
      curative modality. Most patients are candidates for chemotherapy at some point in
      their treatment, but no standard regimen has been established. Several phase II
      single-agent and combination chemotherapy studies have been performed over the
      past 2 decades. Although the true impact of chemotherapy in mesothelioma remains
      to be determined, agents with consistent antitumor activity include doxorubicin,
      platinum agents, and antimetabolites. Combination chemotherapy is associated with
      higher response rates, but not necessarily longer median survivals. Large
      randomized trials, which are currently ongoing or have been performed in the past
      few years, will yield important answers in regard to the role of chemotherapy and
      the efficacy of various single and combination chemotherapy agents. Furthermore,
      the biologic and genetic studies of mesothelioma have identified several receptor
      tyrosine kinases that are aberrantly expressed in these tumors. Orally available
      small molecule inhibitors of several receptor tyrosine kinases have been
      developed and are now being evaluated in clinical trials.

PMID- 14596694
TI  - Molecular fingerprinting in human lung cancer.
AB  - The behavior and outcome of lung cancers are highly variable, and not only is the
      molecular basis of this variability unknown, but neither standard histopathology
      nor currently available molecular markers can predict these characteristics.
      Accordingly, the identification of novel biomarkers to differentiate tumor from
      normal cells and predict tumor behavior such as pathologic stage, response to
      chemotherapy, and site of relapse, is of great importance in clinical practice.
      None of the hundreds of single markers evaluated to date have demonstrated
      significant clinical utility, but by surveying thousands of genes at once with
      use of microarrays or proteomic technologies, it is now possible to read the
      molecular signature of an individual patient's tumor. When the signature is
      mathematically analyzed, new classes of cancer can be observed and insight can be
      gained into prediction, prognosis, and mechanism. Although some success has been
      achieved with genomic approaches, proteomics-based approaches allow examination
      of expressed proteins of a tissue or cell type, complement the genome
      initiatives, and are increasingly being used to address biomedical questions.
      This review aims to summarize the state of the art of gene and protein expression
      profiling for non-small-cell lung cancer

PMID- 14596693
TI  - A phase I study of pegylated liposomal doxorubicin hydrochloride (Caelyx) in
      combination with cyclophosphamide and vincristine as second-line treatment of
      patients with small-cell lung cancer.
AB  - The purpose of this study was to determine the recommended phase II dose of
      liposomal doxorubicin (Caelyx ; Doxil in the United States) in combination with
      cyclophosphamide and vincristine for previously treated patients with good
      performance status with relapsed or refractory small-cell lung cancer. Twenty-one
      eligible patients were enrolled between November 1999 and September 2001 and
      received liposomal doxorubicin 25-40 mg/m2, cyclophosphamide 750-1000 mg/m2, and
      vincristine 1.2 mg/m2 intravenously (I.V.) every 21 days. At doses of liposomal
      doxorubicin 40 mg/m2, cyclophosphamide 750 mg/m2, and vincristine 1.2 mg/m2 I.V.,
      1 of 6 patients had dose-limiting neutropenia and fever in cycle 2 and 2 of 6
      developed grade 3 hand-foot syndrome during cycle 3. Therefore, the recommended
      phase II doses are liposomal doxorubicin 35 mg/m2, cyclophosphamide 750 mg/m2,
      and vincristine 1.2 mg/m2 I.V. every 21 days. Antitumor activity was seen at all
      dose levels. This combination is well tolerated and has evidence of antitumor
      activity. A phase II evaluation is ongoing.

PMID- 14596695
TI  - Imaging lung tumors with peptide-based radioligands.
AB  - The somatostatin analogue octreotide was the first radiopeptide to be used for
      the scintigraphic diagnosis of tumors. Somatostatin receptor scintigraphy (SRS)
      has proven its value, especially in the detection of gut neuroendocrine tumors.
      In some tumor types, it is considered the diagnostic gold standard. In carcinoid
      tumors of the lung, SRS is of major importance in diagnostic workup. Furthermore,
      the combination of computed tomography scanning and SRS is a reliable and cost
      effective approach for the evaluation of single pulmonary nodules. Despite these
      favorable properties, SRS fails in the detection of metastases of lung cancer.
      The problem of false-positive results in SRS resulting from inflammatory disease
      might be overcome by the use of new radiopeptides such as cholecystokinin-B
      receptor-binding gastrin analogues. This article focuses on the current status of
      peptide-receptor scintigraphy in the diagnosis of lung tumors and on future
      developments in this field.

PMID- 14596696
TI  - Early-stage non-small-cell lung cancer: adjuvant versus neoadjuvant chemotherapy.

PMID- 14596697
TI  - 39th Annual Meeting of the American Society of Clinical Oncology: Chicago,
      Illinois, May 30 to June 3, 2003.

PMID- 14596698
TI  - Cisplatin-based adjuvant chemotherapy in resected non-small-cell lung cancer.

PMID- 14596699
TI  - The role of Pemetrexed (Alimta , LY231514) in lung cancer therapy.
AB  - Pemetrexed (Alimta , LY231514) is a new multitargeted antifolate that inhibits
      several enzymes involved in the folate pathway. Pemetrexed is a potent inhibitor
      of thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide
      formyltransferase. Pemetrexed has demonstrated clinical activity in non-small
      cell lung cancer (NSCLC) as well as in a broad array of other solid tumors
      including mesothelioma and breast, colorectal, bladder, cervical, gastric, and
      pancreatic cancer. In NSCLC, single-agent activity has been documented in the
      first- and second-line settings. Promising activity has also been demonstrated
      when pemetrexed is combined with cisplatin, vinorelbine, oxaliplatin,
      carboplatin, and gemcitabine. Low-level dietary supplement of folic acid and
      vitamin B12 has significantly improved the safety profile of pemetrexed without
      compromising its antitumor effect. In this review, the pharmacology and clinical
      activity of pemetrexed in NSCLC cancer is discussed.

PMID- 14596700
TI  - Quality of life and the treatment of advanced lung cancer.
AB  - Lung cancer is the leading cause of cancer deaths worldwide, with the majority of
      patients presenting with advanced disease. Despite the introduction of newer
      therapeutic agents and modest survival improvement, the overall prognosis for
      these patients is poor. The goals of therapy should therefore include improvement
      in quality of life (QOL), palliation of symptoms, and prolongation of survival.
      Quality of life has now become recognized as an important outcome measure for
      cancer therapy. Quality-of-life endpoints are being increasingly incorporated
      into clinical trials of newer agents to further define meaningful response. The
      assessment of QOL involves comprehensive measurement tools that address the
      physical, social, functional, and emotional well-being of the patient. Such
      measurements should be easy to use, meaningful, and relevant to the patients and
      clinician. Although these measures assess the longitudinal impact of treatment on
      QOL, pretreatment QOL scores may also be an important prognostic factor for
      survival in patients with lung carcinoma. This article reviews QOL measures and
      the data for QOL benefits from therapy in patients with advanced small-cell and
      non-small-cell lung cancer.

PMID- 14596701
TI  - Combination treatment with weekly docetaxel and gemcitabine for advanced non
      small-cell lung cancer in elderly patients and patients with poor performance
      status: results of a Minnie Pearl Cancer Research Network phase II trial.
AB  - The purpose of this study was to evaluate the feasibility, toxicity, and efficacy
      of the combination of weekly docetaxel and gemcitabine in patients with advanced
      non-small-cell lung cancer (NSCLC) who are either elderly or have poor
      performance status (PS). Patients with stage IIIB or IV NSCLC who had received no
      previous chemotherapy and were = 70 years of age were eligible for this clinical
      trial. Patients < 70 years of age were also eligible if they had poor PS or were
      considered poor candidates for standard platinum-based combination chemotherapy
      regimens. All patients received chemotherapy with gemcitabine 800 mg/m2 and
      docetaxel 30 mg/m2, both drugs administered by 30-minute intravenous infusions on
      days 1, 8, and 15. Treatment courses were repeated every 28 days. Patients were
      reevaluated after completion of 2 treatment courses; responding patients
      continued treatment until disease progression or for a maximum of 6 courses.
      Between August 1999 and June 2000, 64 patients (73% with stage IV disease) were
      treated at 17 participating sites in the Minnie Pearl Cancer Research Network.
      Eighteen of 64 patients enrolled (28%) had objective response to treatment; an
      additional 25 patients (39%) had stable disease. Median survival was 7 months,
      with 1- and 2-year survival rates of 30% and 17%, respectively. Treatment was
      well tolerated by most patients. Grade 3/4 leukopenia occurred in 7 patients
      (11%), but no patient required hospitalization for neutropenia/fever. One patient
      developed fatal bilateral pneumonitis, which was possibly treatment-related. The
      combination of weekly docetaxel/gemcitabine is active and relatively well
      tolerated in most patients with advanced age or poor PS with advanced NSCLC. A
      randomized comparison of this regimen versus single-agent weekly docetaxel is in
      progress.

PMID- 14596702
TI  - Special patients, special treatments.

PMID- 14596703
TI  - Phase I study of weekly alternating therapy with irinotecan/cisplatin and
      etoposide/cisplatin for patients with small-cell lung cancer.
AB  - The combination of IP (irinotecan/cisplatin) has been shown to confer a survival
      benefit compared with EP (etoposide/cisplatin) in patients with extensive-stage
      small-cell lung cancer (SCLC). Based on this and potential synergy from
      sequential inhibition of topoisomerases I and II, we conducted a phase I study to
      assess the feasibility of weekly therapy alternating IP and EP. The doses of EP
      were fixed (etoposide 60 mg/m2 on days 1-3 and cisplatin 20 mg/m2 on day 1). The
      dose of irinotecan was escalated in serial cohorts at 3 dose levels: 80, 90, and
      100 mg/m2 on day 1. Granulocyte colony-stimulating factor was given on days 2-5
      and days 4-7 after IP and EP, respectively. Patients with limited-stage SCLC
      received chemoradiation during weeks 4-6 with etoposide 120 mg/m2 on days 1-3,
      cisplatin 60 mg/m2 on day 1, and thoracic radiation 1.5 Gy twice daily in 30
      fractions. Patients received 12 weeks of therapy. To evaluate dose escalation in
      subsequent cohorts, dose-limiting toxicity (DLT) was initially assessed during
      weeks 1-3 of treatment. Characteristics of the 18 patients accrued are as
      follows: performance status 0/1, n = 9; female sex, n = 9; extended-stage SCLC, n
      = 16; and median age, 53 years. Four patients treated at irinotecan dose level 1
      (80 mg/m2), 6 patients at dose level 2 (90 mg/m2), and 6 patients at dose level 3
      (100 mg/m2) did not experience DLT in weeks 1-4 and completed therapy without
      major incident. The only 2 patients to experience DLT during weeks 1-4 were
      treated at dose level 2. Both were hospitalized during week 4 and subsequently
      died. However, patients had already been accrued at dose level 3 and tolerated
      therapy well. Therefore, the trial design was modified to assess DLT during weeks
      1-4, and additional patients were cautiously added to the dose level 2 and 3
      cohorts. Analysis of summary toxicity data resulted in a recommendation that dose
      level 3 be used in phase II based on the probability of DLT of 16% (95% CI, 3%
      29%). Responses in 16 evaluable patients include complete response in 1 patient,
      partial response in 14 patients, and minor response in 1 patient. With the
      exception of the 2 deaths, the therapy was well tolerated and active. Phase II
      evaluation of the regimen in patients with extensive-stage SCLC is ongoing.

PMID- 14596704
TI  - The potential contributions of chronic inflammation to lung carcinogenesis.
AB  - A number of lines of evidence suggests that chronic inflammation contributes to
      the process of carcinogenesis. In this article, this theme is explored with
      particular emphasis on the involvement of inflammation in the development of lung
      cancer. A number of molecular pathways activated in chronic inflammation may
      contribute to lung carcinogenesis. The challenge is to conceptualize a cohesive
      picture of this complex biology that allows for effective pharmaceutical
      intervention. Initial therapeutic efforts involve strategies to block single
      pathways, such as with cyclooxygenase (COX) activity. However, the more that is
      learned about the consequences of COX activity, the more evident are the
      relationships of this enzyme to other classes of regulatory molecules such as the
      potent nuclear factor-kB. In light of this emerging picture, more global
      intervention strategies, such as with drug combinations, may be essential for
      success. Further basic study is essential to sort out possible molecular
      relationships and to permit elucidation of the most critical regulatory circuits.
      Given the complexity of these molecular interactions, well-designed clinical
      trials that specifically evaluate the precise effects of particular
      antiinflammatory drugs on lung carcinogenesis will also be critical to sort out
      the complexity and to validate successful approaches to arresting lung
      carcinogenesis.

PMID- 14596705
TI  - Children's concepts of illness: an intervention to improve knowledge.
AB  - OBJECTIVES: This study aimed to explore children's understanding of illness and
      attempted to improve their knowledge through the presentation of a factual story
      and group discussions. DESIGN: Children's responses to questions pertaining to
      three ailment types (contagious illness, non-contagious illness and injury), for
      three process variables (cause, time from cause to effect, and recovery factors),
      were recorded before and after a training intervention. METHOD: Children aged 4
      (N=30) and 7 years old (N=30) were initially individually interviewed about
      common ailments (contagious: chickenpox and cold; non-contagious: asthma and
      cancer; injury: scraped knee and broken arm). A week later half of the children
      in each age group (N=30) were included in a small group (N=5) intervention where
      factual information about three of the ailments was provided and children
      participated in guided group discussions. The remaining control children received
      no intervention. All children were subsequently individually interviewed a week
      later using the initial interview schedule. RESULTS: The 7-year-olds exhibited
      more sophisticated knowledge of illness at pre-test than the 4-year-olds.
      Comparison of pre- to post-intervention changes showed that children who
      participated in the intervention condition improved overall in their
      understanding of the ailments significantly more than controls. However, detailed
      analyses revealed a large degree of variation across the sample in terms of post
      test change for individual items. CONCLUSION: Children's understanding of illness
      is complex and undergoes developmental changes between the ages of 4 and 7.
      Educational interventions that provide age-appropriate factual information and
      peer group discussions regarding illness processes might be effective in
      improving knowledge of illness among young children.

PMID- 14596706
TI  - Influence of attention focus and trait anxiety on tolerance of acute pain.
AB  - OBJECTIVES: In light of inconsistencies in the reported effects of attention and
      anxiety on pain tolerance, this study examined the separate and combined effects
      of attention focus and trait anxiety on tolerance of acute experimental pain.
      DESIGN: Participants with 'high' and 'low' trait anxiety were assigned to three
      attention-focus conditions: pain-focused attention, 'undirected' (no experimenter
      induced attempts to influence attention focus) and distraction. METHODS: Several
      indices of autonomic arousal (systolic and diastolic blood pressure, heart rate
      and EMG) were measured before and during, and several self-report inventories
      were completed before and after, each of two administrations of the cold pressor
      test. RESULTS: In general, pain tolerance was greater when participants were
      distracted and in low- rather than high-anxiety participants. However, attention
      and anxiety interacted such that low-anxiety participants were most pain
      tolerant, and high-anxiety participants were least pain tolerant, in the
      undirected condition. CONCLUSION: The results are consistent with the notion that
      anxiety fosters attentiveness to possible environmental threats, and might have
      implications for the clinical management of acute pain.

PMID- 14596707
TI  - Combining motivational and volitional interventions to promote exercise
      participation: protection motivation theory and implementation intentions.
AB  - OBJECTIVE: This study compared a motivational intervention based on protection
      motivation theory (PMT, Rogers, 1975, 1983) with the same motivational
      intervention augmented by a volitional intervention based on implementation
      intentions (Gollwitzer, 1993). DESIGN: The study had a longitudinal design,
      involving three waves of data collection over a 2-week period, incorporating an
      experimental manipulation of PMT variables at Time 1 and a volitional,
      implementation intention intervention at Time 2. METHOD: Participants (N=248)
      were randomly allocated to a control group or one of two intervention groups.
      Cognitions and exercise behaviour were measured at three time-points over a 2
      week period. RESULTS: The motivational intervention significantly increased
      threat and coping appraisal and intentions to engage in exercise but did not
      bring about a significant increase in subsequent exercise behaviour. In contrast,
      the combined protection motivation theory/implementation intention intervention
      had a dramatic effect on subsequent exercise behaviour. This volitional
      intervention did not influence behavioural intention or any other motivational
      variables. CONCLUSIONS: It is concluded that supplementing PMT with
      implementation intentions strengthens the ability of the model to explain
      behaviour. This has implications for health education programmes, which should
      aim to increase both participants' motivation and their volition.

PMID- 14596708
TI  - A comparison of predictors of the adolescent intention to smoke with adolescent
      current smoking using discriminant function analysis.
AB  - OBJECTIVES: This paper explores one possible operationalization of smoking
      intention to assist development of adolescent smoking intervention programmes.
      Such programmes usually focus on predictors of current smoking, ignoring
      predictors of intentions to smoke, or how intentions relate to actual future
      smoking. DESIGN AND METHODS: Respondents took part in two stages of a repeated
      measures national survey on Australian adolescent smoking behaviour (12-month
      interval between administrations). A total of N=1419 adolescents provided matched
      data, measuring personal smoking habits, intentions of smoking behaviour, stress
      (seven subscales), self-esteem and response to the General Health Questionnaire
      (GHQ-12). RESULTS: A comparison of discriminant function predictors showed
      similarity between the current smoking and intention to smoke, with only one
      predictor differing between the functions. Non-smokers were more behaviourally
      consistent with their stated non-smoking intention over 12 months (i.e. remain
      non-smokers) than smokers (i.e. intention seemed unrelated to actual behaviour).
      CONCLUSIONS: While the predictors give no general indication of whether the
      processes behind the intention to smoke differ from current smoking, the
      intention to smoke may be a better focus for intervention with smokers given the
      apparent inconsistency with stated intention. Intervention for non-smokers may be
      usefully focused on maintaining non-smoking rather than preventing smoking.

PMID- 14596709
TI  - The influence of perceived control over causes and responses to health threats: a
      vignette study.
AB  - OBJECTIVES: To test the hypothesis that a disease caused by controllable,
      compared with uncontrollable, factors is more likely to result in negative
      emotions and less likelihood of disclosure to significant others. DESIGN AND
      METHODS: A between-participants design in which students (N=108) imagined they
      had just been diagnosed with either HIV or hypertension and where the cause for
      each was described as either controllable or uncontrollable. Anticipated
      emotional and behavioural responses by self and others were assessed by
      questionnaire. RESULTS: When the vignette represented a more controllable cause,
      participants thought they would have more negative feelings and that they would
      be less likely to disclose information about the disease to their family or an
      acquaintance than when the vignette represented a less controllable cause. The
      type of disease, but not the cause, influenced anticipated responses by others.
      CONCLUSIONS: Although greater perceived control over future outcomes is often
      psychologically adaptive, these findings suggest that the perception that the
      onset of a disease was controllable may be maladaptive, resulting in more
      negative feelings and a greater reluctance to disclose the diagnosis to others.
      In the light of the increasing use of medical technologies aimed at primary
      prevention of disease, together with a cultural shift toward individual
      responsibility for health, there is a need for greater understanding of how the
      perceived controllability of the cause of a disease affects subsequent
      adjustment.

PMID- 14596710
TI  - Living with vitiligo: dealing with difference.
AB  - OBJECTIVES: Individuals with a disfigurement are at risk of experiencing
      psychological distress, but the level of this distress is only marginally
      associated with clinical severity. This study examines the experience of living
      with the skin condition vitiligo with a view towards understanding its impact and
      the ways in which participants deal with this chronic and disfiguring disease.
      DESIGN: The qualitative method Interpretative Phenomenological Analysis was used.
      METHODS: In a semi-structured interview, seven white female vitiligo sufferers
      were asked to describe their experiences from the time the vitiligo first became
      apparent to the time of the interview. They were encouraged to elaborate on their
      own reactions and how they dealt with the reactions of others. RESULTS:
      Initially, participants felt overwhelmed by their illness but over time they
      developed several strategies in order to 'contain' their difference in appearance
      within manageable limits. The behavioural strategies of avoidance and concealment
      had several disadvantages, whereas cognitive strategies were less problematic but
      difficult to sustain consistently. Social support served to facilitate the
      development of coping methods associated with acceptance of difference. However,
      maintaining this acceptance was a struggle and the process fragile. CONCLUSIONS:
      Living with vitiligo was a continuous struggle. The results are consistent with
      Leventhal's (1970) notion that coping is a problem-solving process and with Moos
      and Schaefer's (1984) contention that dealing with a chronic disease involves the
      development of a variety of strategies in order to regain equilibrium. Further
      research is needed to examine whether the experiences described here are common
      to other disfiguring conditions.

PMID- 14596711
TI  - Do health promotion messages target cognitive and behavioural correlates of
      condom use? A content analysis of safer sex promotion leaflets in two countries.
AB  - OBJECTIVE: To categorize and quantify the content of publicly available safer sex
      promotion leaflets in the UK and Germany and to assess the extent to which this
      content corresponds to the cognitive and behavioural correlates of condom use
      identified by theory-based research. METHODS: A content analysis using a 45
      category coding manual was undertaken. The manual included 20 'correlate
      representative' categories identifying text promoting the strongest cognitive and
      behavioural correlates of condom use. RESULTS: Overall inter-coder reliability
      was high. Few content differences were observed between the German and UK
      samples. Leaflets from both countries highlighted information on how people
      become infected with HIV and advice to contact health care professionals. Few
      mentioned delaying or abstaining from sexual intercourse. Only 25% of leaflets
      included text that referred to more than 10 of the 20 correlate-representative
      categories. Moreover, using one standard deviation above the mean as an
      indication of frequent inclusion, two-thirds of leafets failed to target
      frequently more than two of the 20 correlate-representative categories.
      CONCLUSIONS: Some safer sex promotion leaflets frequently promote the strongest
      cognitive and behavioural correlates of condom use. In general, however, the
      recommendations of researchers investigating psychological correlates of condom
      use have not shaped the content of safer sex promotion leaflets.

PMID- 14596712
TI  - The effect of pre-operative psychological interventions on post-operative
      outcomes in Chinese women having an elective hysterectomy.
AB  - OBJECTIVE: To test the effect of cognitive interventions with information given
      pre-operatively on post-operative outcomes in Chinese women undergoing elective
      hysterectomies. DESIGN: An experimental design. The experimental group (n=48)
      received cognitive distraction and cognitive reappraisal with information, the
      control group (n=48) received information only. OUTCOME MEASURES: Post-operative
      anxiety (Chinese State-Trait Anxiety Inventory and mean arterial blood pressure),
      post-operative requests for analgesia (drug record), post-operative pain (visual
      analogue scale) and satisfaction (Chinese Patient Satisfaction Questionnaire).
      RESULTS: Cognitive distraction and reappraisal with information produced lower
      post-operative anxiety and pain scores and higher levels of satisfaction than
      information only. Post-operative analgesic requests did not differ between
      groups. CONCLUSIONS: Cognitive distraction and reappraisal with information, when
      used with women undergoing a hysterectomy may have significant clinical benefits.

PMID- 14596713
TI  - Ironic processes in the eating behaviour of restrained eaters.
AB  - Theory. The present study examines the processes underlying the disinhibition of
      the eating behaviour of restrained eaters following negative emotions. Based on
      Herman and Polivy's (1984) Boundary Model and Wegner's Ironic Process Theory
      (1994), the limited capacity hypothesis is formulated, suggesting that overeating
      in restrained eaters results from cognitive capacity limitations. Predictions
      were that (1) impairment of cognitive capacity during eating will lead to
      overeating in restrained but not in unrestrained eaters and that (2) this
      difference should only emerge with food perceived to be high in calories.METHOD:
      The hypotheses were tested in an experiment with a 2 (restrained/unrestrained) x
      2 (distraction yes/no) x 2 (perceived calories high/low) design, in which
      subjects consumed ice-cream in a taste test situation. Ice-cream consumption was
      the dependent variable.RESULTS: A second-order interaction was found: as
      predicted, in the high calorie condition restrained eaters ate the same amount as
      unrestrained eaters when not distracted, but considerably more when distracted.
      There was also an unexpected main effect of distraction, which indicated that
      restrained as well as unrestrained eaters ate more if distracted than if not
      distracted.DISCUSSION: The restraintxdistractionxperceived calories interaction
      can be explained by both the Ironic Process Theory and the Boundary Model; and
      the limited capacity hypothesis appears to be confirmed. The overall main effect
      of distraction remains puzzling. Two speculative views for the latter effect are
      offered.

PMID- 14596714
TI  - The prevalence and persistence of depression and anxiety following myocardial
      infarction.
AB  - OBJECTIVES: This study was designed to assess the prevalence and persistence of
      symptoms of depression and anxiety during the first 12 months following acute
      myocardial infarction (MI). DESIGN AND METHODS: In a prospective study, 288 MI
      patients were assessed for symptoms of depression and anxiety using the Beck
      Depression Inventory (BDI) and the State-Trait Anxiety Inventory (STAI) in
      hospital, 2-15 days following MI, and 4 and 12 months subsequently. RESULTS:
      During hospitalization, 89 (30.9%) and 75 (26.1%) patients registered elevated
      BDI scores (>/=10) and state anxiety scores (>/=40), respectively. The 4 and 12
      month prevalence rates were 37.7% and 37.2% for depressive symptoms, and 41.8%
      and 40.0% for anxious symptoms, respectively. Depression and anxiety were highly
      co-morbid, with 51% of patients experiencing significant levels of depressive and
      anxious symptoms at baseline. More than half the patients with complete BDI and
      state anxiety data experienced either elevated symptoms of anxiety or depression
      throughout the first year following MI. CONCLUSIONS: Symptoms of depression and
      anxiety are prevalent, persistent problems during the first year following MI.
      This study highlights the importance of routine psychological assessment for MI
      patients both in hospital and after discharge.

PMID- 14596715
TI  - Environmental illness prevalence: A population-based study in Nova Scotia.
AB  - OBJECTIVES: Clinic studies demonstrate that people diagnosed with environmental
      illness experience high levels of disability and health care utilization. Even
      though the controversial status of this disorder attracts attention, actual
      prevalence estimates and estimated impact on health care systems are unclear. To
      address this, we sought both a prevalence estimate and a measure of the degree of
      health care utilization for those reporting this diagnosis. DESIGN AND METHODS:
      Point prevalence, as assessed by self-report of professional diagnosis, was
      established with data from the Nova Scotia Health Survey 1995, a stratified,
      random sample population survey of 3227 Nova Scotian adults. We compared medical
      care utilization for the year following the survey, drawn from the provincial
      medical insurance register, between the 24 cases with no other reported medical
      conditions and 48 age-, sex-, and education level-matched healthy controls.
      RESULTS: The adjusted point prevalence of environmental illness was 2.6%.
      Physician reimbursement costs across the following year were 5.5 times more
      likely to be above the survey average ($259 CAD) when compared to the healthy
      control group. CONCLUSIONS: The prevalence of environmental illness diagnoses
      represents a significant disability and treatment burden, justifying research
      into case definition and the phenomenology of environmental illness by health
      psychologists.

PMID- 14596716
TI  - An exposure-based examination of the effects of written emotional disclosure.
AB  - OBJECTIVES: We undertook this study to clarify the operative mechanisms that
      account for the relationship between emotional disclosure and health. We
      hypothesized that emotional disclosure via writing was a form of exposure-based
      therapy and that exposure was the active therapeutic component. Design and
      method. A group of 129 male and female undergraduates were randomly assigned to
      three writing groups: (1) a trauma disclosure writing group; (2) a positive
      emotion writing group to control for affect arousal; and (3) a neutral writing
      group to control for any affect arousal - either positive or negative. Process
      measures were taken before and after each 3-day, 20-minute writing session. All
      participants completed questionnaires that assessed psychological and physical
      functioning at both the baseline and the end of the semester (approximately 9
      weeks later). RESULTS: Groups reported differential affective arousal as well as
      disclosure themes in accord with our predictions. We did not replicate the
      findings of Pennebaker and his colleagues (e.g. Pennebaker & Beall, 1986). In our
      study, physical health outcome measures did not differ between groups by the end
      of the semester, nor did psychological measures change from baseline to follow
      up. CONCLUSIONS: We found only limited support for the hypothesis that exposure
      best explains the effects of written self-disclosure. Implications for future
      research in this area are discussed.

PMID- 14596717
TI  - The affective beneficence of vigorous exercise revisited.
AB  - OBJECTIVES: High exercise intensity may be associated with reduced adherence to
      exercise programmes, possibly because it is perceived as aversive. However,
      several authors have suggested that an intensity as high as 60% or 70% of maximal
      aerobic capacity (VO(2max)) is necessary for exercise to elicit positive
      affective changes. To elucidate this discrepancy, the affective responses to
      increasing levels of exercise intensity were examined. DESIGN: In total, 30
      volunteers rated their affect every minute as they ran on a treadmill while the
      speed and grade were progressively increased. METHOD: The methodology was unique
      in three respects: (1) affect was assessed in terms of the dimensions of the
      circumplex model instead of distinct affective states, (2) affect was assessed
      repeatedly before, during, and after exercise, not only before and after, and (3)
      exercise intensity was standardized across participants in terms of metabolically
      comparable phases (beginning, ventilatory threshold, VO(2max)) instead of
      percentages of maximal capacity. RESULTS: Pre-to-post-exercise comparisons
      indicated affective benefits in the form of increased energetic arousal and
      decreased tense arousal. During exercise, however, affective valence deteriorated
      beyond the ventilatory threshold and until VO(2max), a trend that reversed itself
      instantaneously during cool-down. CONCLUSIONS: Exercise intensity that requires a
      transition to anaerobic metabolism can have a transient but substantial negative
      impact on affect and this may, in turn, reduce adherence to exercise programmes.

PMID- 14596718
TI  - Multidimensional fatigue, somatic symptoms and depression.
AB  - OBJECTIVES: Assess the moderating role of somatization on depression in the
      perception of fatigue for a healthy adult population. DESIGN: Correlational
      survey. METHODS: Several fatigue questionnaires, a mental health inventory,
      somatic complaints and demographic data were collected from a targeted, randomly
      selected adult sample (N = 278). RESULTS: Depression levels were positively and
      significantly related to all aspects of fatigue except fatigue that responds to
      rest and sleep (i.e. tiredness). When high levels of depression were coupled with
      somatization, fatigue complaints were more severe. CONCLUSIONS: Even within a non
      patient population, somatization and depression had interactive effects on
      fatigue. Somatization increased fatigue level for the relatively dysphoric
      individuals.

PMID- 14596719
TI  - Negative affect and binge eating in overweight women.
AB  - OBJECTIVES: Binge eating among overweight women is associated with adverse
      physical and psychological consequences, and is known to occur in response to
      negative affect. This study sought to examine the role played by individual
      differences in coping style in the relationship between negative affect and binge
      eating. METHOD: Overweight women (N = 105) completed a battery of questionnaires
      that assessed their binge eating severity, negative affect, and dispositional
      coping style. RESULTS: Women with higher levels of negative affect had more
      severe binge eating problems than those who generally experienced a low level of
      affective distress. Among those who were low in negative affect, however, those
      who tended to use the dysfunctional strategy of disengagement to cope with stress
      reported more severe binge eating than those who reported they were less likely
      to employ this coping style. CONCLUSIONS: The findings from this study emphasize
      the complexity and multicausality of affect-related binge eating in overweight
      women. Prospective studies are required to establish the role of negative affect
      and coping style in the onset and progression of recurrent binge eating among
      overweight individuals.

PMID- 14596720
TI  - Exploring discontinuity patterns in the transtheoretical model: An application of
      the theory of planned behaviour.
AB  - OBJECTIVES: The principal objective of the present paper was to investigate the
      utility of an extended theory of planned behaviour (TPB) for discriminating
      between stages of the transtheoretical model (TTM). DESIGN: Congruent with Sutton
      (2000) a cross-sectional design was employed. The study (N = 331) investigated
      the TPB and TTM in the domain of health-related food choice. METHOD: The study
      utilized a questionnaire methodology. The data were analysed using analyses of
      variance and polynomial contrast analyses. RESULTS: Results showed a significant
      linear trend for all TPB variables across TTM stages, although there were
      significant quadratic relationships between TTM stage and both subjective norm
      and behavioural intention. Hierarchical regression analyses indicated that TTM
      stage might best be regarded as a proxy measure of behaviour. CONCLUSIONS: The
      present study provides evidence to support the utility of the TPB but casts doubt
      on the TTM. Further research is required to evaluate the effectiveness of
      interventions targeted at individuals in certain stages with variables informed
      by the TPB, and to extend the present findings beyond the domain of health
      related food choice.

PMID- 14596721
TI  - Psychological well-being and quality of life in women with an iatrogenic
      hepatitis C virus infection.
AB  - OBJECTIVE: This study documents psychological well-being, mental health and
      quality of life in a group of women diagnosed with an iatrogenic hepatitis C
      (HCV) infection and examines the relationship between HCV RNA status and
      adjustment to their illness. DESIGN: A cross-sectional design was used. METHOD:
      Psychological well-being, mental health and quality of life were assessed in a
      consecutive clinical sample of 93 women who were anti-HCV positive (ELISA, third
      generation). Of these, 33 had a self-limiting HCV infection (HCV RNA negative),
      whereas 60 had chronic HCV infection (HCV RNA positive). RESULTS: Overall,
      psychological well-being and mental health were diminished in all women and were
      best predicted by their level of social functioning, which accounted for between
      42% and 57% of the variance. When comparing women with chronic HCV infection and
      those with a self-limiting HCV infection, no differences were detected in quality
      of life and no association was found between HCV RNA status and a clinical
      diagnosis of depression or anxiety. Furthermore, no significant differences were
      demonstrated in HCV RNA positive women when compared according to liver histology
      on all measures. CONCLUSION: In both HCV RNA positive and HCV RNA negative women,
      high levels of psychological distress and impaired quality of life were found.
      Impairments were not related to HCV RNA status or liver histology.

PMID- 14596722
TI  - Attitudes to doctors and medicine: The effect of setting and doctor-patient
      relationship.
AB  - OBJECTIVE: There have been few studies of attitudes to doctors and medicine,
      despite their potential importance in health psychology. The present study
      examines the effect on attitudes of setting (general practice vs. antenatal) and
      context (specific doctors vs. doctors in general). METHOD: Interview survey of
      167 antenatal attenders and 113 women general practice attenders, using an
      extended form of the Attitudes to Doctors and Medicine Scale of Marteau (1990).
      RESULTS: Although antenatal attenders expressed more positive attitudes to
      doctors and medicine than general practice attenders, differences were small, and
      only statistically significant for 4 of 19 scale items. Compared with ratings of
      doctors in general, however, patients gave much more positive ratings to both
      their family doctor and the antenatal clinic doctors, the latter being rated
      higher than the former. Antenatal doctors were most likely to be rated as good
      doctors, to have the patient's absolute confidence, and to know what was best for
      them (all p<.001). The scale factor structure originally reported by Marteau
      could not be confirmed. DISCUSSION: The results suggest that attitudes to doctors
      and medicine are strongly dependent on whether general stereotypes or particular
      experiences are assessed. They also suggest that the therapeutic context may be
      an important factor in the formation of attitudes.

PMID- 14596723
TI  - Effective approaches to persuading pregnant women to quit smoking: a meta
      analysis of intervention evaluation studies.
AB  - OBJECTIVES: The study aimed to: (1) assess the effectiveness of prenatal smoking
      cessation interventions, (2) clarify whether the psychological changes targeted
      by interventions are related to their effectiveness, (3) identify specific
      intervention components associated with greater effectiveness, and (4) establish
      whether aspects of evaluation methodology are associated with a greater
      effectiveness. DESIGN: Differences in proportions of women quitting and odds
      ratios were calculated for the intervention and control groups. Interventions
      were categorized in relation to the main intervention target (i.e. cognitive
      preparation versus increased threat perception), use of follow-up contact, use of
      individual cessation counselling and other characteristics. Methodological
      approaches to evaluation were also categorized. METHODS: A systematic literature
      review generated 36 controlled evaluations, including one unpublished study. A
      meta-analysis was used to relate study classifications to effectiveness. This
      involved univariate analyses and a multivariate model of the relationship between
      observed univariate effects. RESULTS: A weighted mean odds ratio of 1.93
      indicated a good overall effectiveness. Cognitive preparation interventions
      achieved higher quit rates (6.5%) compared to interventions focusing on threat
      perception (2.2%). However, this effect was not maintained in the multivariate
      analysis. CONCLUSION: Interventions should employ follow-up, but further research
      is required to assess the impact of one-to-one counselling. Clarification of the
      psychological change processes underlying the observed effectiveness of these
      interventions is required. Future research should seek to identify the active
      ingredients and cognitive mediators of successful interventions.

PMID- 14596724
TI  - Stress in chronic disease: do the perceptions of patients and their general
      practitioners match?
AB  - OBJECTIVE: To compare the stressors accompanying chronic disease as perceived by
      patients and their GPs and to explore how incongruence in patients' and GPs'
      ideas influences patients' health status and use of health care. METHOD: A total
      of 580 patients with a diagnosis of diabetes or osteoarthritis and their GPs were
      interviewed by questionnaire about the stressors accompanying a patient's
      illness. In addition, information was obtained from each patient on health status
      and use of health care. RESULTS: The results show that patient and GP diverge in
      the way they think about chronic illness. Incongruence was larger in the case of
      osteoarthritis. In both diabetes and osteoarthritis, incongruence between patient
      and GP was associated with a worse health status of the patient and an increase
      in health-care use, although the pattern of correlation differed by type of
      disease. CONCLUSIONS: A chronic disease requires an ongoing relationship between
      patient and GP over years. Therefore, it is especially important that providers
      recognize the problems with which chronic disease patients are faced. Too often,
      providers are one-sided focused on the medical aspects of disease, neglecting the
      personal impact that a chronic disease has on the patient's life. In this way,
      successful treatment is complicated.

PMID- 14596725
TI  - Social behaviour and illness information interact to influence the peer
      acceptance of children with chronic illness.
AB  - OBJECTIVES: Social behaviour was investigated as a contributor to the peer
      acceptance of children with chronic illness. We predicted that children with
      illness would receive less acceptance than children without illness, and that
      prosocial behaviour would improve acceptance, while aggressive behaviour would
      hamper it. Based upon attribution and cognitive bias theories, we also predicted
      that prosocial behaviour would be more beneficial and aggressive behaviour less
      damaging to the acceptance of children with illness compared to healthy children.
      DESIGN: A 3 (social behaviour: prosocial, aggressive, no information) x 2
      (physical status: chronically ill, healthy) within-subjects analogue design was
      used. METHODS: Preadolescents (N = 149) indicated social acceptance of
      hypothetical children portrayed in vignettes as either chronically ill or healthy
      with prosocial, aggressive, or no social behaviour. A 13-item social intentions
      scale gauged acceptance. RESULTS: The hypotheses were supported. Although
      children described as ill received lower acceptance ratings than healthy
      children, prosocial/ill children were more accepted than aggressive/ill children.
      Social behaviour interacted with physical status to affect acceptance.
      CONCLUSIONS: Social behaviour influences the peer acceptance of hypothetical
      children with chronic illness. Prosocial behaviour enhances acceptance of
      children described with illness, while aggressive behaviour hampers it.
      Additionally, prosocial behaviour is more beneficial, and aggressive behaviour is
      less damaging for children described as ill versus healthy. The potential
      processes by which peers judge acceptance of children with illness are discussed.

PMID- 14596726
TI  - Behavioural treatment for sleep problems in children with severe intellectual
      disabilities and daytime challenging behaviour: effect on mothers and fathers.
AB  - OBJECTIVES: The study aimed to assess the mental state of mothers and fathers
      following successful behavioural intervention for sleep problems in such
      children. DESIGN: A randomized controlled trial of behavioural interventions for
      sleep problems. METHODS: Parents of 15 children with severe intellectual
      disabilities, severe sleep problems, and challenging daytime behaviour received
      treatment for the child's sleep problem and were compared with 15 controls who
      received no treatment. Parental stress, sleepiness, locus of control, perceived
      control, and satisfaction with aspects of sleep were assessed. RESULTS:
      Successful treatment benefited the mothers, reducing stress, increasing perceived
      control and making them more satisfied with their sleep, their child's sleep, and
      their ability to cope with their child's sleep. Positive effects in the fathers
      were limited to increased satisfaction with their own sleep and their child's
      sleep; fathers tended to feel less control following treatment. Maternal
      sleepiness and perceived control, and aspects of parental satisfaction showed
      improvements in both the treatment and control groups. CONCLUSION: The effects of
      childhood sleep problems, and their resolution using behavioural interventions,
      may be different in mothers and fathers. This highlights the need to assess all
      family members in order to gain a greater understanding of how best to help
      families as a whole. The improvements in both control and treatment groups
      indicate that there may be non-specific effects of taking part in the study that
      played a therapeutic role.

PMID- 14596727
TI  - One-year follow-up effects of two obesity treatments on psychological well-being
      and weight.
AB  - OBJECTIVES: The effectiveness of a cognitive and a behavioural treatment for
      obese binge eaters and obese non-binge eaters was evaluated at 1-year follow-up.
      Furthermore, we examined the role of weight changes on psychological well-being
      at 1-year follow-up. DESIGN AND METHOD: Participants were reassessed 6 months and
      1 year after they had finished a group cognitive treatment or a group behavioural
      treatment. The outcome measures were; psychological well-being (concerns about
      shape, weight and eating, self-esteem and depression), binge eating, and weight.
      RESULTS AND CONCLUSIONS: Analyses on the completers' sample revealed that both
      treatments had a markedly positive and lasting impact on shape concern, weight
      concern and eating concern, binge eating, self-esteem, and depression at 1-year
      follow-up. Cognitive treatment was not superior to behavioural treatment on most
      outcome measures. This might be due to selective drop-out. Analyses including non
      responders showed that the cognitive treatment was superior on shape, weight and
      eating concern, and binge eating. The 1-year follow-up results for weight-loss
      were disappointing. Between pre-treatment and 1-year follow-up participants in
      the behaviour treatment lost 3.0 kg, while participants in the cognitive
      treatment lost 0.3 kg. However, participants who gained weight were as successful
      on changes in psychological well-being changes as participants who lost weight.

PMID- 14596728
TI  - Delinquency, health behaviour and health.
AB  - OBJECTIVES: This study investigated the association between delinquency and
      health in a sample of adolescents and young adults (aged 13-24) and examined
      whether the association could have been due to delinquency-related differences in
      demographic, socio-economic and life-style factors. METHOD: The study is based on
      cross-sectional data from a sample of 3677 adolescents and young adults
      interviewed as part of a survey of Dutch households. Health, health behaviour,
      and delinquency were assessed through self-report measures. RESULTS: Delinquency
      was significantly related to three of the four measures of health behaviour
      (smoking, alcohol consumption, and drug use), even after control for demographic
      and socio-economic factors. Delinquency was also significantly associated with
      all three measures of health assessed in this study (somatic symptoms, general
      health, and chronic conditions). However, only minimal support was found for the
      hypothesis that the association between delinquency and health was mediated by
      differences in health behaviour or demographic/socio-economic differences.
      CONCLUSIONS: Adolescent delinquents are less healthy than non-delinquents.
      Potential causes for this relationship are proposed. Possibly, personality
      factors, such as hostility, or psychosocial stress might explain why delinquency
      correlates with health.

PMID- 14596729
TI  - Do self-help interventions in health education lead to cognitive changes, and do
      cognitive changes lead to behavioural change?
AB  - OBJECTIVES: The present study examined the extent to which self-help
      interventions change specific cognitions and the extent to which changes in such
      cognitions are related to behavioural changes. DESIGN: A randomized field
      experiment with follow-ups after 2 weeks and 3 months. METHOD: Smokers (N = 1546)
      were randomly assigned to one of four conditions offering smoking cessation self
      help materials containing (1) outcome information, (2) self-efficacy enhancing
      information, (3) both sorts of information, or (4) no information. RESULTS:
      First, with regard to behavioural effects, only self-help interventions that
      included self-efficacy enhancing information were more effective than no
      information. Second, with regard to the cognitive changes, the data showed that
      outcome information led to increase in expected positive outcomes but also to
      increases in self-efficacy expectations. Further, self-efficacy-enhancing
      information led to increases in self-efficacy. Third, different cognitive changes
      between T1 and T2 were related to different types of quitting activity at T3 in
      different groups of smokers. CONCLUSIONS: Some types of information lead to
      specific cognitive changes, while other types have more generalized cognitive
      effects. Further, cognitive changes produced by a self-help intervention predict
      future quitting activity.

PMID- 14596730
TI  - Predicting exercise stage transitions over two consecutive 6-month periods: a
      test of the theory of planned behaviour in a population-based sample.
AB  - OBJECTIVES: To predict exercise stage transitions over two consecutive 6-month
      periods using the theory of planned behaviour (TPB). It was hypothesized that
      different social cognitive constructs would predict different stage transitions.
      DESIGN: Prospective and longitudinal in order to predict multiple stage
      transitions over time. Assessments were made at baseline, 6 months and 1 year.
      METHOD: Participants were a randomly selected population-based sample of 683
      adults who completed two telephone interviews (baseline and 6 months) that
      assessed exercise stage, intention, perceived behavioural control, attitude,
      subjective norm, and social support, and a mailed survey (1 year) that assessed
      exercise stage. RESULTS: Progression from pre-contemplation was predicted by
      intention, attitude and subjective norm; progression/regression from
      contemplation was predicted by intention, perceived behavioural control,
      attitude, and social support; progression/regression from preparation was
      predicted by intention and attitude; and regression from action/maintenance was
      predicted by intention, attitude and social support. CONCLUSIONS: Different
      social cognitive constructs predicted different stage transitions, which
      indicates that exercise behaviour change may be represented by a series of stage
      transitions. Moreover, the TPB may be a useful model for highlighting the key
      social cognitive constructs that are important for exercise stage transitions.

PMID- 14596731
TI  - Emotional expressivity and intrusive cognitions in women with family histories of
      breast cancer: application of a cognitive processing model.
AB  - OBJECTIVES: Women with family histories of breast cancer exhibit significant
      distress and intrusive cognitions about cancer. The role of intrusive cognitions
      in adjustment to chronic stressors is unclear. While they may be a source of
      distress in themselves, they may also be part of a cognitive processing strategy
      that aids in the adaptation process, particularly if they are accompanied by more
      deliberate processing such as emotional expression. Applying cognitive processing
      models of stress, the present study examined the role of dispositional emotional
      expressivity in intrusive cognitions about breast cancer and distress in women
      dealing with the stressful experience of having a family history of breast
      cancer. Two competing hypotheses were tested: (1) emotional expressivity is
      associated with reduced intrusive cognitions and thus lower distress; (2)
      emotional expressivity buffers the relations between intrusive cognitions and
      distress. DESIGN: Using a cross-sectional design, hypotheses were addressed with
      multiple regression analyses according to established methods. METHOD: Healthy
      women (N = 104) who had one or more first-degree relatives with breast cancer
      were recruited from cancer screening programs. They completed questionnaires
      regarding family history of cancer, emotional expressivity, distress, and
      intrusive cognitions. RESULTS: Emotional expressivity was not associated with
      reduced intrusive cognitions (Hypothesis 1) but moderated the relations between
      intrusive cognitions and distress (Hypothesis 2). CONCLUSIONS: The data further
      our understanding of cognitive processing theories of stress and underline the
      importance of including emotional expression in interventions, helping women to
      process the stressful experiences associated with having family histories of
      breast cancer.

PMID- 14596732
TI  - Perceived stress and coronary heart disease risk factors: the contribution of
      socio-economic position.
AB  - OBJECTIVES: The aim of this study was to explore the relationship between risk
      factors for coronary heart disease (CHD) and perceived stress, adjusted for socio
      economic position. DESIGN: Cross-sectional analysis of CHD risk factors,
      perceived stress and socio-economic position. METHOD: A cohort of employed
      Scottish men (N = 5848) and women (N = 984) completed a questionnaire and
      attended a physical examination. RESULTS: Higher socio-economic groups registered
      higher perceived stress scores. Perceived stress was associated with the
      following CHD risk factors in the expected direction: high plasma cholesterol,
      little recreational exercise, cigarette smoking, and high alcohol consumption.
      Contrary to expectations, stress was related negatively to high diastolic blood
      pressure, body mass index (BMI) and low forced expiratory volume. Correction for
      socio-economic position tended to abolish the associations between stress and
      physiological risk factors; the associations between stress and behavioural risk
      factors withstood such correction. The residual patterns of associations between
      perceived stress and CHD risk were broadly similar for men and women. A lower
      BMI, a greater number of cigarettes smoked, and greater alcohol consumption were
      associated with higher levels of perceived stress for both sexes. Lower levels of
      recreational exercise were associated with higher levels of stress for men only.
      CONCLUSIONS: Self-reported stress is related to health-related behaviours and to
      physiological CHD risk factors. The direction of the association with
      physiological risk was often contrary to expectation and appeared to be largely
      due to confounding by socio-economic position. In contrast, the association with
      health-related behaviours was in the expected direction and was largely
      independent of such confounding.

PMID- 14596733
TI  - The factor structure of the BDI in facial pain and other chronic pain patients: a
      comparison of two models using confirmatory factor analysis.
AB  - OBJECTIVES: 1) To compare two measurement models of the BDI in chronic pain
      sufferers to see which provides the better fit; 2) to assess whether model fit
      differs for a facial pain sample compared to a sample of pain sufferers attending
      a multidisciplinary pain clinic; and 3) to establish which affective and somatic
      sub-scales of the BDI could be used in chronic pain research. DESIGN: Two groups
      of chronic pain sufferers, a facial pain group, and a group attending a
      multidisciplinary pain clinic completed self-report questionnaires on pain
      (Multidimensional Pain Inventory), depression (BDI), and measures of anxiety and
      depression-related pain cognitions (the Spielberger State-Trait Anxiety Inventory
      and the Pain Cognitions Questionnaire). The measurement models of the BDI were
      tested using LISREL structural equation modelling and their construct validity
      examined using partial correlation analysis. METHOD: A total of 173 people
      attending a multidisciplinary pain clinic and 157 patients attending a facial
      pain clinic completed self-report measures of pain and mood prior to their
      respective clinical consultations. RESULTS: The model offered by Novy et al.
      (containing one affective factor 'Negative-attitude suicide' and two somatic
      factors 'Performance difficulty' and 'Physiological manifestations') fitted both
      pain groups better than the model offered by Williams and Richardson (containing
      one affective factor 'Self-reproach', one somatic factor 'Somatic disturbance'
      and one factor with a mixture of both affective and somatic items 'Sadness about
      health'). However, when the factors were allowed to correlate in the latter
      model, both models were broadly equivalent. CONCLUSIONS: The two measurement
      models adequately fitted data in both pain samples when the factors were allowed
      to intercorrelate in the Williams and Richardson model. Both the affective scales
      offered by both models could be used in future research, although the somatic
      factor offered by the Williams and Richardson model offered much higher levels of
      internal reliability than either of those offered in the Novy et al. model. The
      findings are discussed in relation to the issue of depression in chronic pain.

PMID- 14596734
TI  - Psychophysiological effects of relaxation training in children.
AB  - OBJECTIVES: This study compares the effects of progressive muscle relaxation and
      an imagery-based relaxation training on childrens' physiological and subjective
      responses in a randomized controlled trial. DESIGN: Sixty-four children aged 9 to
      13 years were randomly allocated to either one of three experimental conditions:
      progressive muscle relaxation, imagery-based relaxation or a control condition
      (neutral story). There were five training sessions in each condition. METHOD:
      Heart rate (HR), skin conductance level (SCL), and skin temperature (ST) were
      measured continuously during a 5-minute baseline period, an 8-minute relaxation
      training period, and a 5-minute follow-up in each session. In addition,
      subjective ratings of mood and physical well-being were collected intermittently.
      RESULTS AND CONCLUSIONS: A physiological pattern indicating relaxation was most
      clearly associated with the imagery-based relaxation approach (decreases in HR
      and SCL), although ST remained unchanged. In contrast, progressive muscle
      relaxation led to an increase in HR during the training. The neutral story
      condition showed a similar trend as the imagery-based relaxation approach
      (although not reaching statistical significance). Furthermore, children's ratings
      of positive mood and physical wellbeing increased during baseline and training
      periods, but there were no differences between training conditions. The results
      indicate psychophysiological effects of relaxation instructions which, however,
      are not specific for systematic relaxation training.

PMID- 14596735
TI  - Acne: a biopsychosocial and evolutionary perspective with a focus on shame.
AB  - PURPOSE: Hypotheses regarding the psychological factors implicated in the
      development and maintenance of acne first emerged in the middle of the eighteenth
      century. However, the psychodermatological literature from this date relating to
      acne has variously been described as confusing, overly prone to conjecture and,
      in particular, atheoretical. The current paper has two key objectives; first, to
      present a biopsychosocial model of acne development and maintenance and,
      secondly, to understand the psychosocial strain imposed by acne from an
      evolutionary perspective with a particular emphasis on body shame reactions.
      METHODS: The psychodermatological literature relating to acne is reviewed with
      the data analysed for potential biopsychosocial interactions and shame eliciting
      responses. RESULTS: The review indicates that acne can be reconceptualized as a
      biopsychosocial phenomena which, in turn, provides the field with innovative
      hypotheses for empirical inquiry and the potential for expanding and evaluating
      treatment options. The evolutionary analysis illustrates that acne provides the
      potential for distressing body shame reactions due to the skin disease's
      potential for damaging self-other evaluations of attractiveness. CONCLUSIONS:
      Acne has tended to be viewed as a minor dermatological complaint which imposes
      minimal psychological distress upon sufferers. The paper concludes that acne has
      the ability to elicit in some sufferers significant mental health concerns due to
      a heightened sense of shame relating to appearance.

PMID- 14596736
TI  - Self-efficacy and goal importance in the prediction of physical disability in
      people following hospitalization: a prospective study.
AB  - OBJECTIVES: This prospective study evaluates the role of self-efficacy and goal
      importance in predicting decreases in disability in activities of everyday
      living. METHOD: Disability, self-efficacy and goal importance were each assessed
      before and at 3 and 9 months after participants underwent joint replacement
      surgery. RESULTS: Disability had decreased at 3 and 9 months post-surgery
      assessments. Self-efficacy beliefs were higher at 3 and 9 months following
      surgery while goal importance was increased at 9 months but not at 3 months.
      Medical variables and prior disability predicted disability at 3 months. Social
      cognitive variables did not contribute to the prediction of 3 months disability.
      Pre-surgery goal importance and self-efficacy at 3 months were independent
      predictors of disability at 9 months after controlling for pre-surgery and 3
      months disability. Evidence also suggested that goal importance and self-efficacy
      interacted to predict levels of disability at 9 months following surgery.
      CONCLUSIONS: The findings demonstrate that recovery is governed not solely by
      medical phenomena but also by psychological variables and suggest that
      modification of these variables may have an impact on recovery outcomes.
      Moreover, attention should be paid to the timing of such intervention and to the
      length of follow-up.

PMID- 14596737
TI  - Psychological factors associated with short-term recovery from total knee
      replacement.
AB  - OBJECTIVE: To identify the psychological factors that predict short-term recovery
      following total knee replacement. METHOD: A group of 42 patients undergoing total
      knee replacement received a pre-operative psychological assessment. Four self
      report questionnaires were completed: the Pain Coping Strategies Questionnaire;
      the Short Form Social Support Questionnaire; the Recovery Locus of Control Scale;
      and the Brief Symptom Inventory. Post-operative outcome was assessed in terms of
      the number of days taken to achieve key physiotherapy milestones (straight leg
      raise; 90 degrees bend of the knee) and discharge. RESULTS: The three response
      variables were analysed separately using an ordinal regression. Internal locus of
      control was associated with a shorter time to achieve a straight leg raise.
      Larger values of catastrophizing were associated with longer times to achieve a
      90 degrees bend. There was a trend towards larger values of satisfaction with
      social support to be associated with an earlier achievement of the 90 degrees
      bend. No psychological variables were found to be associated with the length of
      hospital stay. CONCLUSIONS: As suggested by previous studies, coping style and
      locus of control appear to be important in the rehabilitation process. The
      current data suggest that psychological variables could be usefully included in a
      pre-operative assessment for total knee replacement.

PMID- 14596738
TI  - Ambivalence about health-related behaviours: an exploration in the domain of food
      choice.
AB  - OBJECTIVES: Interest in attitudes and ambivalence has highlighted problems with
      the adequacy of conceptualizing attitudes as unitary, unidimensional,
      evaluations. In this paper, we report an application of the Theory of Planned
      Behaviour (Ajzen, 1991) in the domain of dietary choice which investigates the
      hypothesis that ambivalence will attenuate observed attitude-intention
      relationships (since the evaluations influencing the expression of attitudes are
      more likely to differ from the evaluations influencing the expression of
      intentions for people who are more ambivalent. DESIGN: Participants completed a
      postal questionnaire which contained, inter alia, measures assessing the
      components of the Theory of Planned Behaviour and a measure of ambivalence.
      METHODS: Participants (N = 296) were recruited via advertisements placed in local
      newspapers, asking for volunteers to assist in a research project. Participants
      were randomly assigned to complete a questionnaire about either their chocolate
      consumption or their meat consumption. Participants were paid  4. RESULTS: The
      findings show considerable support for the hypothesis: there was a tendency for
      attitude-intention relationships to be attenuated among participants with higher
      levels of ambivalence, compared to participants with lower levels of ambivalence.
      CONCLUSIONS: The research supports the widespread view that ambivalence is an
      important issue, both for those involved in basic attitude research and for those
      who seek to use attitude theories in applied research. In particular, the
      findings indicate that ambivalence may often have implications for the predictive
      ability of attitude-intention-behaviour models, especially when applied to health
      related behaviours that are characterized by motivational conflicts.

PMID- 14596739
TI  - Factors associated with self-disclosure of HIV serostatus to significant others.
AB  - OBJECTIVES: To examine rates and patterns of self-disclosure of HIV serostatus
      amongst individuals attending an out-patient HIV clinic in East London. DESIGN: A
      cross-sectional survey design was used. METHODS: A volunteer sample of 95 out
      patient HIV clinic attendees completed a self-report questionnaire examining
      patterns of disclosure to self-identified significant others, reasons for
      disclosure and non-disclosure, satisfaction with social support (SSQ6), quality
      of life (MOS-30) and anxiety and depression (HADS). Self-disclosure was examined
      in relation to cultural background, gender, satisfaction with social support, and
      medical and psychological variables. RESULTS: Seventy-nine men and 16 women
      reported a mean disclosure rate of 68% to self-identified significant others.
      Five individuals had not disclosed their HIV status to anyone; 91% of individuals
      had informed their partner. Friends were more frequently informed (79%) than
      family (53%). Ethnicity (p <.001) and length of time since testing HIV
      seropositive (p <.05) emerged as significant predictors of disclosure. Global
      satisfaction with social support was negatively correlated with depression but
      was not associated with the total rate of HIV disclosure. Frequently reported
      reasons for non-disclosure included wanting to protect others from distress and
      fear of discrimination. CONCLUSIONS: Self-disclosure of HIV serostatus rates was
      highest for partners, followed by friends, and lowest for family members.
      Patterns of disclosure of HIV serostatus varied in relation to ethnicity. Fifteen
      years into the HIV epidemic, social stigma continues to contribute towards non
      disclosure of diagnosis.

PMID- 14596740
TI  - Spontaneous, elicited and cued causal attributions in the year following a first
      myocardial infarction.
AB  - OBJECTIVES: To assess myocardial infarction (MI) patients' causal beliefs, how
      they change over time and the effects of different assessment methods. METHOD:
      The study used a longitudinal design with a follow-up to 1 year. The participants
      were 100 MI patients who were recruited within 72 hours of admission. Each
      participant was interviewed and their causal attributions (spontaneous, elicited
      and cued) were assessed using four different methods. RESULTS: 'Stress',
      'smoking', 'it is in the family', 'eating fatty foods' and 'work' items were the
      most commonly mentioned causes for the MI at all times of measurement and across
      all measures. On each occasion 'stress' and 'smoking' were selected as the most
      important causes and patients made fewer attributions over time. Finally, the
      attributional assessment method used did not affect type of attributions but
      fewer attributions were reported using the spontaneous method. CONCLUSION:
      Patients do provide causal attributions following an MI. While many are similar
      to causal factors identified by medicine, patients appear to place more emphasis
      on 'stress'. As predicted by attribution theory, attributions changed over time.
      The method of obtaining the attributions does not appear to affect the
      attributions made but greatly affects their number. While all the methods used
      have their place, the cued method with a list of possible attributions offers a
      rich return for effort expended.

PMID- 14596741
TI  - Convergent evolution: the academic and policy roots of collaborative research.

PMID- 14596742
TI  - Health services research and development in practice: an Australian experience.
AB  - While there is a growing literature on how health services research can inform
      health policy decisions, the practical challenge is for health services
      researchers to develop an effective interface with health policy-making processes
      and to produce outputs that lead to outcomes. The experience of the Centre for
      Health Service Development at the University of Wollongong, Australia, is used to
      illustrate the issues so commonly described in the literature and to reflect on
      our experience of trying to remain viable while producing relevant and valid
      research. A case study in a specific policy area - namely, the development of
      case-mix classifications and information systems to inform policy and funding in
      the subacute and non-acute hospital and community care sectors - is used as a
      practical example of the research-policy interface.

PMID- 14596743
TI  - Linkage and exchange at the organizational level: a model of collaboration
      between research and policy.
AB  - This paper describes an organization-level initiative designed to promote linkage
      and exchange between a research unit and the mental health policy branch of
      Ontario's provincial government. Using a framework that conceptualizes four tiers
      -inter-organizational relationship, interactive research projects, dissemination
      and policy formation--in the application of linkage and exchange to the research
      and policy development processes, we present an example in order to explore the
      issues that arise in each tier. We conclude that while such initiatives enhance
      the relevance of research in the policy development process, they also present
      challenges that must be recognized and managed.

PMID- 14596744
TI  - Toward a communicative perspective of collaborating in research: the case of the
      researcher-decision-maker partnership.
AB  - In the shift to a post-industrial order, the production and use of knowledge is
      gaining greater importance in a world beyond science. Particularly in the health
      sciences, research foundations are emphasising the importance of translating
      research results into practice and are experimenting with various strategies to
      achieve this outcome, including requiring practitioners to become part of funded
      research teams. In this paper, we present a case of a partnership between
      researchers and decision-makers in Canada who collaborated on an investigation of
      implementing change in health care organisations. Grounded in this case and
      recent empirical work, we propose that such research collaborations can be best
      understood from a communicative perspective and as involving four key elements:
      relational stance that researchers and decision-makers assume toward each other;
      purpose at hand that situates occasions for developing and using knowledge;
      knowledge-sharing practices for translating knowledge; and forums in which
      researchers and practitioners access knowledge. Our analyses suggest that
      partnerships are most effective when researchers see the value of contextualising
      their work and decision-makers see how this work can help them accomplish their
      purpose at hand.

PMID- 14596745
TI  - Partnership experiences: involving decision-makers in the research process.
AB  - OBJECTIVES: To describe researchers' experiences with involving health system
      managers and public policy-makers (i.e. decision-makers) in the research process,
      and decision-makers' experiences with the research process, including their
      assessments of the benefits and costs of the involvement, and their
      recommendations for facilitating it. METHODS: We conducted semi-structured
      interviews with principal investigators and research staff for the seven research
      programmes funded by the Canadian Health Services Research Foundation in the 1999
      and 2000 competition years, and with the decision-makers they involved in the
      research programmes. RESULTS: We identify three models of decision-maker
      involvement--formal supporter, responsive audience, and integral partner--each of
      which yielded important contributions to the research process. Four factors--the
      stage of the research process, time commitment required, alignment between
      decision-maker expertise and programme needs, and an existing relationship
      between the researcher and decision-maker--influenced the role played by decision
      makers. CONCLUSIONS: While on balance a beneficial experience, the further
      promotion of decision-maker involvement in the research process should involve
      helping researchers and decision-makers identify strategic opportunities for
      decision-maker involvement and support the costs associated with the involvement.
      Consideration should also be given to undertaking and evaluating interactions
      between researchers and decision-makers outside of the research process.

PMID- 14596746
TI  - Implementation of an innovative grant programme to build partnerships between
      researchers, decision-makers and practitioners: the experience of the Quebec
      Social Research Council.
AB  - OBJECTIVES: This paper examines a grant programme developed by the Quebec Social
      Research Council in the 1990s to encourage the building of research partnerships
      between researchers, decision-makers and practitioners. In particular, it studies
      the perceptions of key participants concerning the reasons behind the programme's
      successful implementation and growth. METHODS: In addition to secondary data
      about institutional involvement in the programme, 10 researchers and
      administrators were consulted as key informants. The method of concept mapping
      was used in order to draw out a consensus on the different factors associated
      with the successful implementation of the programme. RESULTS: The participants
      identified 10 main factors that help explain the programme's successful
      implementation. These factors were then grouped into a model containing four
      dimensions: the leadership and coherence shown in the programme's implementation;
      the presence of a favourable political and social conjuncture; the programme's
      responsiveness to the needs of health and social services institutions; and the
      programme's responsiveness to the needs of the university milieu. CONCLUSIONS:
      Although this model remains specific to the prevailing situation in Quebec at the
      time of its application, it may help stimulate reflection and contribute to an
      understanding of how research policies can encourage partnerships between
      researchers, practitioners and decision-makers.

PMID- 14596747
TI  - Creating a new articulation between research and practice through policy? The
      views and experiences of researchers and practitioners.
AB  - OBJECTIVES: In 1990, the Quebec Social Research Council - a body financing social
      research in Quebec, Canada - launched a new policy encouraging the development of
      social research units within health care organizations. Through financial
      incentives, it encouraged the implementation of long-term collaborations between
      researchers and practitioners with the purpose of transforming both scientific
      knowledge production and professional practices. This paper examines the
      perceptions of researchers and practitioners regarding the attributes and the
      usefulness of this collaborative research policy. METHODS: A self-administered
      survey was sent to all the researchers (n = 146; response rate 78.1%) and
      practitioners (n = 204; response rate 44.1%) involved in the 21 collaborative
      research teams funded in 1998. T-tests were performed in order to assess the
      difference between the perceptions of researchers and practitioners in five key
      dimensions of collaborative research. RESULTS: The results showed that, contrary
      to expectations, researchers and practitioners shared fairly similar views
      regarding the various dimensions of collaborative research. They both agreed that
      their involvement within collaborative research teams had contributed to the
      development of new skills and practices but had not facilitated their
      participation in external activities nor their involvement in networks and
      organizations that influence environments in which public policies and practices
      are deployed. They also both encountered some difficulties in putting the
      dimensions that they highly valued into practice. CONCLUSIONS: Collaborative
      research within health care organizations succeeded in fostering the
      implementation of new modes of knowledge production and intervention.
      Nevertheless, special attention needs to be given to the development of
      strategies to reduce the discrepancies between values and practices.

PMID- 14596748
TI  - Novel mode of knowledge production? Producers and consumers in health services
      research.
AB  - OBJECTIVES: To investigate (1) what type of knowledge production characterizes
      health services research - academically based (mode 1) or socially distributed
      (mode 2); (2) how leaders in health services research link to users of the
      research; (3) how this research is influenced by its funding base; and (4) the
      development and dissemination strategies of investigators. METHODS: Four
      purposively selected case studies of contrasting health services research groups
      generated early propositions (70 interviews). These led to a postal survey of key
      stakeholder groups in one English National Health Service region (199 responses,
      53% response rate). RESULTS: Health services research in the UK is characterized
      by: a mix of mode 1 and mode 2 output indicators; strong external relationship
      building by group leaders; a powerful driver from external finance; and extensive
      dissemination and development activity. CONCLUSIONS: Health services researchers
      may have to operate in both modes. Mode 1 retains considerable defensive power,
      so there are limits to the extent to which mode 2 research may develop.

PMID- 14596749
TI  - Increasing research impact through partnerships: evidence from outside health
      care.
AB  - There is growing interest in using closer partnerships between researchers and
      research users to increase the appropriate application of research evidence in
      policy and practice. While this supplement reports and assesses a number of these
      initiatives in health care, this article reviews the evidence in support of
      partnerships from elsewhere. Drawing on a substantial cross-sector review of
      research impact initiatives, we extract lessons for health care from partnership
      evaluations in social care, education and criminal justice services. A reasonable
      and robust evidence base supports the use of partnerships as one means of
      increasing research uptake. Although requiring substantial investments of time,
      resources and commitment, and suffering from a number of possible pitfalls, we
      conclude that such partnerships offer great potential for increasing research
      use.

PMID- 14596750
TI  - Sharing and expanding academic and practitioner knowledge in health care.
AB  - The purpose of this paper is to expand understanding of academic-practitioner
      knowledge-sharing in the service of enhanced knowledge creation in health care.
      To this end, we describe the tacit and explicit knowledge of academics and
      practitioners and how this knowledge exists within their communities of practice.
      We also discuss benefits of, difficulties with, and some underlying dynamics of
      academic-practitioner knowledge-sharing. We then propose what might be done,
      based on appreciation of these dynamics, to foster joint knowledge-sharing and
      knowledge creation. We illustrate our arguments with examples from health care
      settings.

PMID- 14596751
TI  - Regulation of health care markets.

PMID- 14596752
TI  - 'The new localism': once more through the revolving door?

PMID- 14596753
TI  - Priority-setting and hospital strategic planning: a qualitative case study.
AB  - OBJECTIVES: To describe and evaluate the priority-setting element of a hospital's
      strategic planning process. METHODS: Qualitative case study and evaluation
      against the conditions of 'accountability for reasonableness' of a strategic
      planning process at a large urban university-affiliated hospital. RESULTS: The
      hospital's strategic planning process met the conditions of 'accountability for
      reasonableness' in large part. Specifically: the hospital based its decisions on
      reasons (both information and criteria) that the participants felt were relevant
      to the hospital; the number and type of participants were very extensive; the
      process, decisions and reasons were well communicated throughout the
      organization, using multiple communication vehicles; and the process included an
      ethical framework linked to an effort to evaluate and improve the process.
      However, there were opportunities to improve the process, particularly by giving
      participants more time to absorb the information relevant to priority-setting
      decisions, more time to take difficult decisions and some means to appeal or
      revise decisions. CONCLUSION: A case study linked to an evaluation using
      'accountability for reasonableness' can serve to improve priority-setting in the
      context of hospital strategic planning.

PMID- 14596754
TI  - Variation in unit costs of hospitals in the English National Health Service.
AB  - OBJECTIVES: In England, the Department of Health places high priority on reducing
      the variation in unit costs of National Health Service (NHS) hospitals.
      Efficiency targets are set for hospitals to create incentives for relatively high
      cost hospitals to reduce their costs and shift performance closer to that of
      their lower cost counterparts. We examine empirically the dispersion in unit
      costs to assess the extent of variation in the productivity of hospitals and
      trends over time. METHODS: We use econometric panel data techniques on data from
      235 NHS acute hospital trusts over a six-year period, 1994/95 to 1999/00,
      supplemented with information from semi-structured interviews with key
      individuals in hospitals and purchasing bodies. RESULTS: There appears to have
      been no reduction in variation during this period. Relative unit costs for
      individual trusts also appear stable, with little movement from relatively high
      cost to low cost. Judging from limited quantitative evidence outside health care,
      the variation in costs between NHS hospitals may be comparatively low.
      CONCLUSIONS: Given all the other aspects of hospital performance that government
      is seeking to change, reduction in the dispersion of unit costs per se should not
      be a major policy objective. It is far more important to examine variation in
      quality-adjusted unit costs.

PMID- 14596755
TI  - Including a 'no active intervention' arm in surgical trials is possible: evidence
      from the CLasP randomised trial.
AB  - OBJECTIVES: To examine the impact of including a 'no active intervention' arm
      (called 'conservative management') in a randomised controlled trial comparing
      treatments (including surgery) for men with lower urinary tract symptoms related
      to benign prostatic enlargement. METHODS: Outcomes 7.5 months after randomisation
      were acceptability of randomisation, overall acceptability of and satisfaction
      with conservative management, impact on quality of life, perceived need for
      further treatment and treatment failure (defined a priori). RESULTS: In total,
      177 (out of 755) patients refused randomisation, including 31% who did not want
      surgery and 22% who wanted surgery. Most men randomised to conservative
      management were willing to undertake it as part of a trial but at the end of the
      trial they were divided between those who wanted to continue with it and those
      who expected surgery. At follow-up, 39% of conservative management patients
      requested surgery, and interference of symptoms with life and an unsuccessful
      outcome were more commonly reported in this arm. There were no appreciable
      differences between treatment groups in terms of treatment failures. CONCLUSIONS:
      Including a 'no active intervention' arm did not appear to have a detrimental
      effect on patient recruitment or the completion of this trial in the short-term;
      overall, conservative management was successfully completed by the majority of
      patients during the trial period, suggesting that researchers need not avoid
      including a no-intervention arm in surgical trials as long as they take care with
      its presentation.

PMID- 14596756
TI  - Conspicuous consumption: characterizing high users of physician services in one
      Canadian province.
AB  - OBJECTIVES: To examine medical care use and costs, patterns of morbidity and co
      morbidity, and other patient characteristics of high users of physician services
      in British Columbia. METHODS: This population-based study uses physician claims,
      hospital discharge summaries and vital statistics data linked at the level of the
      individual to compare characteristics of high users, other users and non-users of
      physician services in the Province of British Columbia, Canada. The study
      included all enrolled adults in the universal health care plan during fiscal year
      1996/97. High users were defined as the most costly 5% of users of fee-reimbursed
      services. Key variables included age, sex, an ecological socio-economic status
      indicator and a comprehensive set of morbidity indicators, derived from the
      diagnoses recorded on the utilization records. RESULTS: The top 5% of users
      consumed a disproportionate 30% of spending on physician services. High users
      were overwhelmingly characterized by a significant burden of morbidity. Over 80%
      had at least six different types of morbidity during the study year compared with
      fewer than 20% of other users. High users were also much more likely to have
      major diagnoses that were both acute and chronic in nature. Co-morbidity
      involving psychosocial and chronic medical conditions was also very common.
      CONCLUSIONS: High users of physician services are overwhelmingly characterized by
      multiple and complex health problems. Policy tools based on a philosophy of
      deterrence such as cost-sharing are unlikely to have much impact on their costs
      and will likely do considerable harm.

PMID- 14596757
TI  - Beyond demographic change in human resources planning: an extended framework and
      application to nursing.
AB  - OBJECTIVES: To introduce health care production functions into human resources
      planning and to apply the approach to analysing the need for registered nurses in
      Ontario during a period of major reduction in inpatient capacity. METHODS:
      Measurement of changes in services delivered by acute care hospitals in Ontario
      between 1994/95 and 1998/99, and comparison with changes in the mix of human
      resources, non-human resources and patient needs. RESULTS: Inpatient episodes per
      nurse fell by almost 2%. At the same time the number of beds was cut by over 20%.
      As a result, the number of patients per bed increased by 12%. Allowing for
      severity, there was a 20% reduction in beds per episode and a 3.7% reduction in
      nurses per episode. CONCLUSIONS: The demands on nurses in acute care hospitals
      have increased as an increasing number of severity-adjusted episodes are served
      using fewer beds by a reduced number of nurses. Human resources planning
      traditionally only considers the effects of demographic change on the need for
      and supply of health care. Failure to recognize the variable and endogenous
      nature of other health care inputs leads to false impressions about the adequacy
      of existing supplies of human resources. Consideration of human resources in the
      context of the production function for health services provides a meaningful way
      of improving the effectiveness and efficiency of human resources planning.

PMID- 14596758
TI  - Efficiency and productivity change in the English National Health Service: can
      data envelopment analysis provide a robust and useful measure?
AB  - OBJECTIVE: Several tools are available to health care organisations in England to
      measure efficiency, but these are widely reported to be unpopular and unusable.
      Moreover, they do not have a sound conceptual basis. This paper describes the
      development and evaluation of a user-friendly tool that organisations can use to
      measure their efficiency, based on the technique of data envelopment analysis
      (DEA), which has a firm basis in economic theory. METHODS: Routine data from 57
      providers and 14 purchasing organisations in one region of the English National
      Health Service (NHS) for 1994-1996 were used to create information on efficiency
      based on DEA. This was presented to them using guides that explained the
      information and how it was to be used. They were surveyed to elicit their views
      on current measures of efficiency and on the potential use of the DEA-based
      information. RESULTS: The DEA measure demonstrated considerable scope for
      improvements in health service efficiency. There was a very small improvement
      over time with larger changes in some hospitals than others. Overall, 80% of
      those surveyed gave high scores for the potential usefulness of the DEA-based
      measures compared with 9-45% for existing methods. The quality of presentation of
      the information was also consistently high. CONCLUSIONS: There is dissatisfaction
      with efficiency information currently available to the NHS. DEA produces
      potentially useful information, which is easy to use and can be easily explained
      to and understood by potential users. The next step would be the implementation,
      on a developmental basis, of a routine DEA-based information system.

PMID- 14596759
TI  - The economics of direct-to-consumer advertising of prescription-only drugs:
      prescribed to improve consumer welfare?
AB  - According to economic theory, one might expect that the informational content of
      direct-to-consumer advertising of prescription-only drugs would improve
      consumers' welfare. However, contrasting the models of consumer and market
      behaviour underlying this theory with the realities of the prescription-only drug
      market reveals that this market is distinct in ways that render it unlikely that
      advertising will serve an unbiased and strictly informative function. A review of
      qualitative evidence regarding the informational content of drug advertising
      supports this conclusion. Direct-to-consumer prescription drug advertising
      concentrates on particular products, and features of those products, to the
      exclusion of others, and the information provided has frequently been found to be
      biased or misleading in regulatory and academic evaluations. Governments that
      have so far resisted direct-to-consumer advertising should invest in independent
      sources of evidence that could help consumers and professionals to better
      understand the risks and benefits of treating disease with alternative drug and
      non-drug therapies, rather than permitting direct-to-consumer prescription drug
      advertising.

PMID- 14596760
TI  - We still need to ask 'what is disease?'.

PMID- 14596761
TI  - Changing the lens: widening the approach to primary care research.
AB  - After years of being shielded from most of the managerial and organisational
      changes in health care, primary care is going through a period of change in many
      countries. Much of the research that has been done in primary care, in common
      with that in secondary care, puts at the centre of its methodology the concept of
      professionalism. However, there are other ways of theorising medical work, and
      using a wider range of theoretical 'lenses' when planning research into the
      impact of change will enhance and enrich that research. Viewing primary care
      physicians as 'workers', concerned, like other workers, with constructing
      understanding of what they do that helps them cope with pressures and
      uncertainties, shifts the focus of research questions away from issues of
      professional status towards the practical ways in which they deal with change in
      their local contexts. Research using this theoretical approach may be able to
      explain phenomena that other, more broad-brush approaches cannot.

PMID- 14596763
TI  - For-profit ownership of facilities would lead to a more efficient health care
      system.

PMID- 14596765
TI  - HIV-related lung cancer -- a growing concern?
AB  - There is an increasing awareness of the importance of non-AIDS-defining
      malignancies occurring in HIV-seropositive people since the introduction of
      highly active antiretroviral therapy (HAART). Amongst these tumours, lung cancer
      occurs at an increased frequency compared to age- and gender-matched populations
      and this increase is not accounted for by smoking alone. Moreover, the incidence
      of lung cancer in people with HIV is rising as overall survival improves due to
      HAART. The development of lung cancer is not associated with a low CD4 cell
      count, suggesting that immune function has a less central role in these tumours
      than in Kaposi's sarcoma and primary cerebral lymphomas. Most patients present
      with advanced stage lung cancer and the outcome is very poor. In contrast to the
      AIDS-defining malignancies, the prognosis in HIV-associated lung cancer does not
      appear to be improving in the era of HAART. Thus lung cancer and possibly other
      non-AIDS-defining malignancies may become an increasingly frequent problem whose
      prognosis has not improved in the era of HAART.

PMID- 14596766
TI  - Innate and adaptive immunological insights into HIV pathogenesis.
AB  - The human immunodeficiency virus is notorious for its ability to evade the immune
      system. As well as its ability to escape from cell-mediated and humoral immune
      responses, new insights are detailing its subversive, pernicious interactions
      with the innate immune system. The molecular mechanisms underlying these
      processes highlight potential therapeutic and vaccination strategies.

PMID- 14596767
TI  - Medical workforce speciality review for genitourinary medicine 2002/2003:
      England, Wales, Northern Ireland and Scotland.
AB  - This document is an updated version of that produced in October 2001 and
      addresses medical workforce needs for the speciality of genitourinary medicine
      (GUM) for the next 10 years. Data on current consultant numbers, working patterns
      and retirement are based on information from the Royal College of Physicians
      (RCP) Workforce Unit annual census undertaken on 30 September 2001. Information
      on specialist registrars (SpRs) is from the Joint Committee on Higher Medical
      Training and the GUM Specialist Registrars Group. Senior house officer data are
      from the RCP's General Professional Training department. Data on non-consultant
      career grade doctors is from the Association of Genitourinary Medicine Survey and
      the GUM Non-Consultants Career Grade Group. Data on incidence of sexually
      transmitted infections (STIs) are from KC60 returns on STIs collected from GUM
      clinics by the Communicable Diseases Surveillance Centre. There is considerable
      movement of doctors in GUM between countries in the UK both during progression
      from SpR to consultant and at the consultant level. Data are therefore presented
      as amalgamated UK data and also by country (Table 1). It is essential that
      workforce planning takes this lateral movement into consideration when
      undertaking calculations for future workforce requirements. The speciality
      continues to have inadequate consultant numbers and funding is also required to
      provide adequate number of non-consultant career grade sessions.

PMID- 14596768
TI  - Chlamydia trachomatis infection in a colposcopy unit: an audit of a fast track
      referral system for infected patients to a genitourinary medicine department and
      a survey of patients' demography, clinical findings and partner details.
AB  - We had previously shown that screening and treating patients for Chlamydia
      trachomatis prior to termination of pregnancy significantly reduces postoperative
      morbidity. Our success led us to consider screening women attending our
      colposcopy unit and this was introduced in 1998. However, it became apparent that
      a formal protocol was needed for managing women who had positive results to
      ensure that all patients and their partners were adequately treated. An
      interdepartmental protocol was devised for fast track referral of infected
      patients to the Genitourinary Medicine (GUM) clinic Health Advisor who arranged
      immediate treatment and partner notification. A re-audit, presented here, has
      shown that the introduction of the protocol has resulted in all infected patients
      receiving adequate treatment and partner notification with minimal use of doctor
      time or disruption of routine GUM services. We suggest that our system is
      effective and could be extended to other clinics where chlamydia screening is
      carried out.

PMID- 14596769
TI  - Do STD clinics correctly diagnose STDs? An assessment of STD management in Hefei,
      China.
AB  - The main purposes of the study were to assess the accuracy of laboratory testing
      and the diagnosis by physicians in sexually transmitted disease (STD) clinics in
      Hefei, China. Among 347 men complaining of urethral discharge or dysuria, 240
      tested positive at the National Centre for either Neisseria gonorrhoeae or
      Chlamydia trachomatis, 310 tested positive according to the clinic laboratories,
      and 347 were diagnosed by the physicians. For chlamydia, the sensitivity and
      positive predictive value (PPV) of the clinic laboratories were 55% and 26%, and
      for the diagnosis by the physicians were 61% and 24%. Laboratory testing and the
      diagnosis by the physicians had low power to detect mixed infection. The PPVs for
      the diagnosis by the physicians were 50% for syphilis and 43% for herpes simplex
      virus (HSV), indicating that both syphilis and HSV were over-diagnosed. Over half
      of those previously infected had not received education to prevent reinfection.
      Thus, the quality of clinic laboratory testing was not high and physicians often
      misdiagnosed STDs.

PMID- 14596770
TI  - The use of complementary and alternative medicine by persons with HIV infection
      in Europe.
AB  - Between June 1996-September 1997 and December 1998-December 1999, two surveys
      using an anonymous questionnaire were carried out in Europe among persons living
      with HIV infection. The questionnaire included questions on use of
      antiretrovirals, complementary or alternative medicines. Vitamins/minerals were
      taken by 528 (58%) of the 1996-97 participants, compared to 326 (63%) of the 1998
      99 participants (P =0.06). Homeopathy was taken by respectively 176 (21%) and 55
      (14%) (P =0.003) participants and herbal products respectively by 213 (25%) and
      77 (20%) (P =0.06). In multiple regression analysis a longer time since HIV
      diagnosis, having a higher education level and having a lower CD(+) lymphocyte
      count were associated with the use of homeopathy. A longer time since HIV
      diagnosis and a more advanced stage of the disease were associated with the use
      of herbal products. The study shows that despite the availability of highly
      active antiretroviral therapy many people with HIV infection still take
      complementary and alternative medicine.

PMID- 14596771
TI  - A computerized reminder system improves compliance with Papanicolaou smear
      recommendations in an HIV care clinic.
AB  - Current guidelines call for Papanicolaou (Pap) smear screening of HIV-infected
      women at least annually. After the initiation of a weekly computer based Pap
      smear reminder list in an HIV care clinic, the prevalence of scheduled women with
      up-to-date Pap smears was calculated for the one-year project period and was
      compared to the prevalence preceding the project. The prevalence of scheduled
      women with up-to-date Pap smears increased from 61.4% to 73.2% (P <0.001) during
      the project period. Including Pap smears that were performed elsewhere, the final
      up-to-date Pap smear rate was 82.7%. The improved rate of up-to-date Pap smears
      showed no sign of attenuation over time. A computerized report generated from
      data in the hospital information system increased rates of compliance with Pap
      smear screening recommendations. Creative utilization of hospital data
      environments may be an inexpensive route to improved compliance with practice
      guidelines.

PMID- 14596773
TI  - Social and behavioural determinants of consistent condom use among hotel and bar
      workers in Northern Tanzania.
AB  - Bar and hotel workers (n=519) in Moshi, Tanzania were interviewed to obtain
      information about potential predictors of condom use. Samples were collected for
      the diagnosis of sexually transmitted diseases (STDs), including HIV. Consistent
      condom use was defined as always using condoms with sexual partners in the past
      five years. Overall consistent condom use in this population was 14.1%. In
      multivariate analyses, consistent condom use was inversely associated with low
      condom self-efficacy (adjusted odds ratio [AOR], 0.20; 95% confidence interval
      (CI), 0.06-0.71), low condom knowledge (AOR, 0.11; CI, 0.01-0.80), and having
      more than three children (AOR, 0.23; 95% CI, 0.09-0.54). Other significant
      predictors included perceived condom acceptability and using condoms when last
      exchanged sex for money or gift. These results indicate that increased specific
      condom knowledge, improved self-efficacy, and reduced social stigma could be
      effective strategies in the promotion of condom use in this population.

PMID- 14596772
TI  - The Bali STD/AIDS study: human papillomavirus infection among female sex workers.
AB  - Female sex workers in low priced brothel areas in Denpasar, Bali, Indonesia
      participated in an intervention study designed to promote condom use and sexually
      transmitted disease (STD)/AIDS prevention. The intervention provided educational
      sessions for sex workers, STD treatment for sex workers, condom distribution, and
      media for clients. The brothel areas were divided into high and low areas for
      programme effort. The high effort areas received a more intensive behavioural
      intervention than the low effort areas. A clinic was available for STD treatment
      in both areas. Behavioural surveys and STD testing were used to evaluate the
      programmes. About 600 were evaluated for several STDs and completed personal
      interviews at enrolment and at six-month intervals during the 18-month study.
      About 50% of women were new to the study at each round. Human papillomavirus
      (HPV) testing of cervical swabbed specimens, using polymerase chain reaction
      methodology, was performed at the beginning of the study and 18 months later.
      Human papillomavirus infection was initially high in these women (38.3%) and
      declined to 29.7% after 18 months (P <0.01). The prevalence of HPV infection
      declined with age (P <0.01). HPV infection was associated with a number of STD
      symptoms that were reported in personal interviews. These associations were
      stronger in the first time period. Infection with Neisseria gonorrhoeae was
      associated with HPV infection at baseline (P =0.03). HPV infection declined in
      the study area with the more intensive educational programme (P <0.01). The
      prevalence of HPV infection declined over time and was associated with study area
      and age of woman.

PMID- 14596774
TI  - Estimating the prevalence of syringe-borne and sexually transmitted diseases
      among injection drug users in St Petersburg, Russia.
AB  - Injection drug users (IDUs) are the vanguard of the human immunodeficiency virus
      (HIV) epidemic in Russia. We sought a non-invasive method to estimate a point
      prevalence of HIV, hepatitis B virus (HBV), hepatitis C virus (HCV), syphilis and
      risk behaviours in IDUs attending the syringe exchange programme (SEP) in St
      Petersburg, Russia. One hundred and one IDUs returning syringes to the St
      Petersburg SEP were invited to complete a questionnaire requesting demographic,
      knowledge, and behavioural information, and to provide their syringes for
      antibody testing. The median age of IDUs was 23 years. Syringe prevalences were:
      10.9% for HIV, 78.2% for HCV, 15.8% for HBV, and 6.9% for syphilis. All
      respondents recognized drug-related risk factors for getting AIDS. Only two
      thirds of subjects recognized condoms to prevent sexually transmitted infections
      and half knew that oil-based lubricants are not appropriate for condoms. The IDU
      population studied was young and requires additional interventions to encourage
      safer sexual behaviours.

PMID- 14596775
TI  - AIDS, HIV and STD among Japanese and Japanese-Americans in San Francisco,
      California, USA.
AB  - In affluent countries, some people may go abroad specifically for HIV testing or
      care for greater anonymity, better treatment, and less discrimination. A
      secondary analysis of data from the San Francisco Department of Public Health was
      conducted to characterize trends in AIDS incidence, AIDS care, sexually
      transmitted disease (STD) incidence, and HIV counselling and testing among
      Japanese in San Francisco. A total of 96 AIDS cases were diagnosed among ethnic
      Japanese, of whom 32 were born in Japan. From 1985 to 2000, 144 gonorrhoea and
      chlamydia cases were identified among Japanese. Of 368 self-identified Japanese
      seeking HIV counselling from 1995 to 1997, three (0.9%) were HIV-positive. The
      HIV/AIDS and STD epidemics among Japanese in San Francisco temporally parallels,
      but lags behind in magnitude, the epidemics for San Francisco's population as a
      whole. Some persons from Japan actively seek HIV/STD services while abroad. Our
      study points to several areas needing further research and improvements.

PMID- 14596776
TI  - Have a nice day -- do a wart audit.
AB  - We performed an audit of the treatment of genital warts at our clinic by
      reviewing the case notes of 302 patients who presented with a first episode of
      genital warts. 186 were suitable for inclusion, of whom over 90% were clear of
      warts within three months. However, even after just one month of treatment, 84.9%
      of men and 60.2% of women were clear of warts. On the basis of this information,
      we can be more optimistic when advising patients about the likely duration of
      treatment.

PMID- 14596777
TI  - Wernicke's encephalopathy in AIDS: a preventable cause of fatal neurological
      deficit.
AB  - Wernicke's encephalopathy is commonly associated with chronic alcohol abuse, but
      may also occur in patients with poor nutritional status. We report a case of
      acute Wernicke's encephalopathy in a patient with AIDS without any predisposing
      risk factors for thiamine deficiency. In developing countries, without vitamin
      supplementation, this disorder may play a role in the morbidity and mortality
      associated with AIDS. We believe that thiamine supplementation should be
      considered in cachetic AIDS patients, especially where access to antiretroviral
      therapy is limited.

PMID- 14596778
TI  - Urinary tract infection in patients with acute non-gonococcal urethritis -- 1.

PMID- 14596780
TI  - Screening for non-gonococcal urethritis.

PMID- 14596781
TI  - Gel and polymer-solution mediated separation of biopolymers by capillary
      electrophoresis.
AB  - In the age of genomics and proteomics, high-resolution separation techniques are
      routinely utilized in an integrated and automated fashion to solve formidable
      separation problems and provide the means for large-scale analysis of biological
      samples with excellent resolution. By automating the current manual procedures,
      capillary gel (CGE) and polymer-solution mediated electrophoresis greatly enhance
      the productivity of biopolymer analysis while also reducing both analysis time
      and the human intervention necessary from sample loading to data processing. The
      advent of this novel and high-performance bioseparation technique has made it
      possible to sequence the human genome and revealed global changes in the genome
      and proteome level, bringing about a revolutionary transition in our views of
      living systems on the molecular basis. CGE and polymer-solution mediated
      electrophoresis and related microseparation methods (e.g., electrophoresis
      microchips) are quickly becoming important separation and characterization tools
      in analytical biochemistry and molecular biology. This review gives an overview
      of the key application areas of DNA, protein, and complex carbohydrate analysis,
      and summarizes the latest developments on CGE column technology, including
      capillary coatings and sieving polymer matrices. Micropreparative aspects and
      related microseparation techniques are also discussed.

PMID- 14596782
TI  - HPLC separation of tetracycline analogues: comparison study of laser-based
      polarimetric detection with UV detection.
AB  - A sensitive and specific high-performance liquid chromatography (HPLC) method
      based upon laser-based polarimetric detection is developed for the determination
      of six tetracycline analogues. By interfacing the laser-based polarimeter online
      with an HPLC system, the specific rotation of each analogue is obtained as
      compounds elute from the separation system. The six structurally similar
      tetracycline analogues exhibit significant differences in specific rotations. The
      experiments suggest that specific rotation can be useful in identifying closely
      related tetracycline analogues. Linear relationships are found to be in the range
      of 0.342-0.0043 mg for the tetracycline analogues. Five of the six analogues
      exhibit excellent linearity (R(2) value >/= 0.99). The polarimetric results are
      compared with UV detection. The HPLC-laser-based polarimetric detection
      instrument is able to quantitate the studied tetracycline analogues with high
      precision, accuracy, and sensitivity, which make it useful for the development of
      a standard method for the determination of tetracyclines in biological specimens.
      The performance of the HPLC-polarimetric system for the analysis of tetracyclines
      in a biological matrix is evaluated. The selectivity of polarimetric detection
      provides a distinct advantage in the analysis of tetracycline analogues in milk.
      The HPLC-polarimetric system provides a rapid and sensitive technique that
      involves minimal sample cleanup and pretreatment for the analysis of
      tetracyclines in milk.

PMID- 14596783
TI  - Mathematical models of solute retention in gas chromatography as sources of
      thermodynamic data. Part III. Alkylbenzenes as the test analytes.
AB  - Direct determination of thermodynamic data has always been a complicated and
      troublesome experimental task. Gas chromatography is among long-established
      working tools well suited to performing this particular task indirectly. Our own
      results were first presented in the papers by Ciazynska-Halarewicz and Kowalska
      (1,2), and this article is Part III in the series. Present experiments are
      carried out on low- and medium-polarity stationary phases at five different
      temperatures ranging from 323K to 423K. They enable determination of two
      thermodynamic properties of the alkylbenzenes, molar enthalpy of vaporization
      (DeltaH(vap)), and the chemical potential of partitioning of the methylene group
      between the two phases of the chromatographic system (Delta micro (p(-CH2-))).
      These properties are obtained from eight nonempirical models and, as is apparent
      from their derivation (3-7), the terms of the models have clearly defined
      physical meaning, which enables calculation of thermodynamic properties.

PMID- 14596784
TI  - A novel stationary phase: capillary-channeled polymer (C-CP) fibers for HPLC
      separations of proteins.
AB  - A novel stationary phase is demonstrated for the separation of proteins.
      Capillary-channeled polymer (C-CP) fibers provide a stationary phase that is
      characterized by a high surface activity (yielding strong wicking action) and
      drastically reduced back pressures. Columns prepared by pulling approximately
      1200 50- micro m diameter polypropylene C-CP fibers through stainless steel
      tubing with column dimensions of 4.6-mm i.d. and 306-mm length exhibit reversed
      phase characteristics in the separation of the proteins. A gradient method [95:5
      water-acetonitrile (ACN)/propanol (1:1) to 35:65 water-ACN/propanol] with
      trifluoroacetic acid added as an ion-pairing agent yields high-quality
      separations of superoxide dismutase, hemoglobin, hemocyanin, and myoglobin. It is
      believed that the C-CP fiber stationary phase holds a number of promising traits
      for applications in both analytical and prep-scale separations of diverse organic
      species, including a wide range of biomolecules.

PMID- 14596785
TI  - Evaluation and characterization of a commercial immunosorbent cartridge for the
      solid-phase extraction of phenylureas from aqueous matrices.
AB  - The behavior and main characteristics of a commercial immunosorbent (IS)
      cartridge for the solid-phase extraction of phenylureas are determined in this
      work. The measured capacity for the analyte-antigen (isoproturon) in a new
      cartridge is 215 ng and, after more than 100 adsorption-desorption cycles, the
      remaining capacity still is approximately 70 ng, demonstrating the good stability
      of the bonded antibody and the interesting possibility of extensive cartridge
      reuse. Only isoproturon and diuron are specifically retained in this sorbent. The
      weak nonspecific retention of other pesticides, including other phenylureas, can
      be avoided by increasing the sample volume during the loading step. Thus, a very
      selective and sensitive method for the determination of isoproturon and diuron in
      natural and potable waters is developed by loading a 50-mL sample adjusted to pH
      7.4 in the IS cartridge, eluting with methanol-water (60:40, v/v), and analyzing
      the eluate by high-performance liquid chromatography with UV detection. The clean
      chromatograms, low detection limits (approximately 0.1 micro g/L), and good
      precision (< 5%) obtained with this rapid and simple method demonstrate that
      immunoaffinity extraction can be an excellent alternative for sample preparation
      in the environmental monitoring of particular pesticides in water matrices.

PMID- 14596786
TI  - Multistep purification of an antifreeze protein from Ammopiptanthus mongolicus by
      chromatographic and electrophoretic methods.
AB  - Antifreeze proteins (AFPs) are known as thermal hysteresis proteins, which can
      depress the freezing points of the solution by noncolligative effects, but do not
      affect the melting points. Although some AFPs have been found in some plants, the
      identity of most proteins remains unclear, owing to insufficient quantity and
      quality to characterize them. In this report, we describe the purification of an
      AFP from the winter leaves of Ammopiptanthus mongolicus using a combination of
      column chromatography and gel electrophoresis. After homogenization in ascorbate
      acid-containing Tris buffers (pH 7.4) the soluble proteins are captured by
      (diethylamino)ethyl-cellulose 52 material. An elution with 0.1-0.3M KCl leads to
      a crude active fraction. The crude fraction is further purified on a Superdex 75
      prep-grade column and finally a Poros 20HP2 column. A complex, consisting of two
      proteins with relative molecular masses of 34,700 and 37,100, respectively, in
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis, is obtained
      by this protein purification protocol. The recovery of two proteins from the gel
      is carried out by electrophoresis. The purified protein, with a molecular mass of
      37,100, shows thermal hysteresis activity (THA) and can modify the normal growth
      of ice crystals. The THA of this purified antifreeze protein is 0.24 degrees C at
      the concentration of 5 mg/mL.

PMID- 14596787
TI  - A high-performance liquid chromatographic-tandem mass spectrometric method for
      the determination of cethromycin (ABT-773) in human plasma, bronchoalveolar
      lavage fluid, and alveolar cells.
AB  - A method is developed for the specific and sensitive determination of cethromycin
      concentrations in plasma, bronchoalveolar lavage (BAL), and alveolar cells (AC),
      using a high-performance liquid chromatographic-tandem mass spectrometry (MS)
      method. The mobile phase consists of 50% acetonitrile-0.05% acetic acid-5mM
      ammonium acetate; the column used is a C(8) reversed-phase stationary phase. The
      preparation of samples requires a solvent extraction step. The retention times
      for cethromycin and the internal standard are approximately 2.0 and 2.7 min,
      respectively, with a total run time of 3.5 min. Detection is carried out using
      electrospray MS in a multiple reaction monitor mode. The detection limits for
      cethromycin are 1 ng/mL for plasma and 0.2 ng/mL for BAL supernatants and AC
      suspensions. The assay has excellent performance characteristics and has been
      used to support a study of the intrapulmonary pharmacokinetics of cethromycin in
      human subjects.

PMID- 14596788
TI  - Location, location, location: new avenues to determine the function of the
      cardiac Na+-Ca2+ exchanger?

PMID- 14596789
TI  - Localization and function of the Na+/Ca2+-exchanger in normal and detubulated rat
      cardiomyocytes.
AB  - It is controversial whether the Na+/Ca2+-exchanger (NCX) can induce cardiomyocyte
      contraction through reverse-mode exchange and Ca2+-induced Ca2+ release (CICR).
      Information about the spatial distribution and functional activity within
      different sarcolemmal (SL) regions could shed light on this potential role. We
      raised a new antibody to the NCX and showed by confocal laser scanning microscopy
      (CLSM) that immunoreactivity is strongly expressed throughout the surface SL and
      intercalated disk regions with punctate labeling of the vertical transverse (T)
      tubules but not the longitudinal T-tubules. Immuno-electron microscopy confirmed
      CLSM observations. Gold particles associated with the exchanger were within
      nanometer range of particles signaling ryanodine receptors. A similar close
      association was found between the L-type Ca2+ channel (known to be concentrated
      in the dyad) and ryanodine receptors. In whole-cell patch-clamped cardiomyocytes,
      peak I(NCX) (measured at 90 mV) decreased by approximately 40% (497 +/- 32 vs.
      304 +/- 12 pA, P < 0.001) after detubulation, while membrane capacitance
      decreased by 27% (204 +/- 11 vs. 150 +/- 7 pF, P < 0.01) thus giving a small but
      significant 16% reduction in current density. Thus, the density and/or functional
      activity of the NCX is greater in the vertical T-tubules than in the longitudinal
      T-tubules, surface SL or disk regions, pointing to important functional
      differences between these plasma membrane domains. Our combined co
      immunolocalization and physiological data suggest that the NCX has multiple
      functions depending upon membrane location. We suggest the possibility that NCX
      modulates CICR, sarcoplasmic reticulum Ca2+ load, and that it also serves to
      regulate Ca2+ handling in neighboring cells.

PMID- 14596790
TI  - Heart mitochondria contain functional ATP-dependent K+ channels.
AB  - Recent observations challenged the functional importance or even the existence of
      mitochondrial ATP-dependent K+ (mitoK(ATP)) channels. In the present study, we
      determined the presence of K(ATP)-channel subunits in mouse heart mitochondria,
      and investigated whether known openers or blockers of the channel can alter
      mitochondrial membrane potential. Investigation of the channel composition was
      performed with antibodies against K(ATP)-channel subunits, namely the
      sulfonylurea receptor (SUR1 or SUR2) and the inwardly rectifying K+ channel
      (Kir6.1 or Kir6.2). Specific Kir6.1 and Kir6.2 proteins were found in the
      mitochondria by western blotting and immunogold electron microscopy. Neither SUR1
      nor SUR2 was present in the mitochondria. In contrast, a mitochondrially enriched
      low molecular weight SUR2-like band was found at approximately 25 kDa.
      Mitochondrial-transport tags were identified in the sequences of Kir6.1 and
      Kir6.2, but not in SUR1 or SUR2. The fluorescent BODIPY-glibenclamide labeling of
      mitochondria indicated direct sulfonylurea binding. Pharmacological
      characterization of mitoK(ATP) was performed in isolated respiring heart
      mitochondria. Fluorescent confocal imaging with the membrane potential-sensitive
      dye MitoFluorRed showed that glibenclamide application changed membrane
      potential, while the specific mitoK(ATP)-channel openers, diazoxide or BMS
      191095, reversed the effect. Mitochondrially formed peroxynitrite is a
      physiological opener of the channel. We conclude that a functional K(ATP) channel
      is present in heart mitochondria, which can be opened by diazoxide or BMS-191095.
      The channel can be composed of Kir6.1 and Kir6.2 subunits and does not contain
      either SUR1 or SUR2.

PMID- 14596791
TI  - A novel activation process of protein kinase C in the remote, non-ischemic area
      of an infarcted heart is mediated by angiotensin-AT1 receptors.
AB  - BACKGROUND: Translocation and activation of protein kinase C (PKC) has been shown
      to occur in the ischemic heart. It is, however, controversial if this activation
      process occurs also in the non-ischemic, remote area of an infarcted heart early
      after infarction. Furthermore, the mechanisms contributing to the translocation
      process induced by acute myocardial ischemia in both areas are not fully
      elucidated. METHODS: Regional myocardial infarction was induced by left anterior
      descending coronary artery (LAD-) ligation in situ for 2.5 min in rats or in
      pigs. To evaluate the influence of angiotensin and bradykinin signaling,
      ramiprilat, candesartan, or the bradykinin-receptor antagonist HOE 140 was given.
      In biopsies from the ischemic and the non-ischemic remote area, PKC activity and
      intracellular isozyme distribution were determined. RESULTS: Translocation and
      activation of PKC could be demonstrated for the first time in the myocardium
      remote from the infarcted area. This activation was conserved both in pigs and in
      rats. All major cardiac isozymes of PKC were involved. Whereas bradykinin
      receptor blockade had no effect, both angiotensin-converting enzyme inhibition
      (ACEI) and angiotensin receptor could effectively block this activation process
      of PKC. CONCLUSION: In the area remote from a myocardial infarction, the
      activation of PKC could be detected for the first time as early as 2.5 min after
      LAD ligation. This newly characterized activation in the non-infarcted area can
      be prevented by ACEI via an angiotensin-AT1-receptor-dependent mechanism. It is
      supposed that this newly characterized activation process of PKC plays an
      important role in the signal transduction in the remote myocardium in acute
      myocardial infarction as a trigger for the late development of hypertrophy and
      heart failure.

PMID- 14596792
TI  - FLIP protects cardiomyocytes from apoptosis induced by simulated
      ischemia/reoxygenation, as demonstrated by short hairpin-induced (shRNA)
      silencing of FLIP mRNA.
AB  - Cardiomyocytes exposed to ischemia followed by reperfusion undergo apoptosis,
      some of which is induced via the mitochondrial pathway, and some of which is
      induced via the death-receptor ligand pathway. FLICE-inhibitory protein (FLIP) is
      a cellular protein that, in overexpression experiments in other cell types, has
      been shown to be capable of either inducing or protecting from death-receptor
      mediated apoptosis, depending on the extent of overexpression. To examine the
      role of endogenous FLIP in neonatal cardiomyocytes we have used short hairpin
      induced (shRNA) silencing generated from a transfected plasmid. Silencing of FLIP
      increases the background level of apoptosis detected by TUNEL assay in primary
      cardiomyocytes and sensitizes the cells to apoptosis induced by simulated
      ischemia/reoxygenation (IR). This result indicates that previous observations of
      decreased FLIP levels and increased apoptosis in cardiac infarcts is more than
      just correlative, but reflects an innate protective role of FLIP in
      cardiomyocytes. We also found that mitochondrial activity, as determined by
      MitoTracker red staining, is reduced in the absence of FLIP, and further
      decreases after exposure to simulated IR. Conversely, overexpression of FLIP
      somewhat prevents the decrease in mitochondrial activity after simulated IR.
      Thus, FLIP may confer protection from simulated ischemia/reperfusion through more
      than one pathway.

PMID- 14596793
TI  - Phosphorylation of human cardiac troponin I G203S and K206Q linked to familial
      hypertrophic cardiomyopathy affects actomyosin interaction in different ways.
AB  - cAMP-dependent protein kinase (PKA)-dependent phosphorylation of the two serine
      residues in the amino terminal region unique to cardiac troponin I (cTnI) is
      known to cause two effects: (i) decrease of the maximum Ca2+-controlled thin
      filament-activated myosin S1-ATPase (actoS1-ATPase) activity and mean sliding
      velocity of reconstituted thin filaments; (ii) rightward shift of the Ca2+
      activation curves of actoS1-ATPase activity, filament sliding velocity, and force
      generation. We have studied the influence of phosphorylation of human wild-type
      cTnI and of two mutant cTnI (G203S and K206Q) causing familial hypertrophic
      cardiomyopathy (fHCM) on the secondary structure by circular dichroism
      spectroscopy and on the Ca2+ regulation of actin-myosin interaction using actoS1
      ATPase activity and in vitro motility assays. Both mutations slightly influence
      the backbone structure of cTnI but only the secondary structure of cTnI-G203S is
      also affected by bis-phosphorylation of cTnI. In functional studies, cTnI-G203S
      behaves similarly to wild-type cTnI, i.e. the mutation itself has no measurable
      effect and bis-phosphorylation alters the actoS1-ATPase activity and the in vitro
      thin filament motility in the same way as does bis-phosphorylation of wild-type
      cTnI. In contrast, the mutation K206Q leads to a considerable increase in the
      maximum actoS1-ATPase activity as well as filament motility compared to wild-type
      cTnI. Bis-phosphorylation of this mutant cTnI still suppresses the maximum actoS1
      ATPase activity and filament sliding velocity but does no longer affect the Ca2+
      sensitivity of these processes. Thus, these two fHCM-linked cTnI mutations,
      although reflecting similar pathological situations, exert different effects on
      the actomyosin system per se and in response to bis-phosphorylation of cTnI.

PMID- 14596794
TI  - Lysophosphatidylcholine regulates human microvascular endothelial cell expression
      of chemokines.
AB  - The role of lysophosphatidylcholine (LPC) in the induction of MCP-1, IL-8 and
      RANTES, which are chemotactic factors to monocytes, neutrophils and lymphocytes,
      respectively, by human vascular endothelial cells (EC), was examined. LPC induced
      the expression of MCP-1 and IL-8 in a concentration- and time-dependent manner in
      microvascular EC (MVEC) and in large vessel EC from aorta, pulmonary artery and
      umbilical vein. LPC also induced RANTES in MVEC but not in large vessel EC.
      Signaling pathways responsible for LPC induction of chemokines were examined in
      MVEC. LPC and TNFalpha, a cytokine secreted in sites of inflammation, additively
      stimulated RANTES expression. LPC did not augment TNFalpha induction of MCP-1 or
      IL-8. A platelet-activating factor receptor antagonist (BN52021) failed to block
      LPC induction of MVEC chemokines, but the G(i)-protein inhibitor pertussis toxin
      partially blocked LPC induction of RANTES and IL-8. LPC activated multiple
      kinases in MVEC; it increased the phosphorylation of ERK1/2, AKT and p38 MAP
      kinase in a time-dependent manner. An inhibitor of the MAPK/ERK pathway, PD98059,
      blocked the phosphorylation of ERK1/2 and RANTES induction by LPC, but augmented
      IL-8 induction. LY294002, a specific inhibitor of phosphoinositide 3 kinase (PI3
      kinase), blunted the phosphorylation of AKT and inhibited LPC induction of RANTES
      more strongly than IL-8. Inhibition of p38 MAP kinase pathway by SB202190 also
      blocked LPC-induced expression of IL-8 and RANTES. Our results suggest that LPC
      induction of chemokines in MVEC is distinct from that in large vessel EC, and
      required the activities of MAP kinases and PI3 kinase for the induction of RANTES
      and IL-8. We speculate that the presence of LPC, a bioactive lipid product of
      phospholipase A(2) (PLA(2)) and a constituent of oxidized low-density
      lipoprotein, can differentially influence the chemotaxis of particular leukocyte
      subpopulations during inflammation.

PMID- 14596795
TI  - De novo design of a molecular switch: phosphorylation-dependent association of
      designed peptides.
AB  - The de novo design of peptides that switch their oligomerization state in
      response to a chemical stimulus is of interest, both as a tool for understanding
      the basis of molecular switching as well as development of reagents for the study
      of signal transduction in cells. The target of the current study is the design of
      a series of peptides that undergo a transition from an unstructured monomer to a
      four-helical bundle upon phosphorylation by the enzyme cyclic AMP-dependent
      protein kinase (PKA). The designed peptides are based on the 20-residue Lac
      repressor tetramerization domain. Beginning with this structure, we introduced a
      phosphorylation site near the N terminus. Phosphorylation leads to a 2-4.6
      kcal/mol increase in the stability of the tetramer, depending on the design. The
      most successful switches were designed such that phosphorylation would increase
      the stability of the individual helices and also relieve an unfavorable
      electrostatic interaction in the tetramer.

PMID- 14596796
TI  - SegG endonuclease promotes marker exclusion and mediates co-conversion from a
      distant cleavage site.
AB  - Bacteriophages T2 and T4 are closely related T-even phages. However, T4 genetic
      markers predominate in the progeny of mixed infections, a phenomenon termed
      marker exclusion. One region previously mapped where the frequency of T2 markers
      in the progeny is extremely low is located around gene 32. Here, we describe
      SegG, a GIY-YIG family endonuclease adjacent to gene 32 of phage T4 that is
      absent from phage T2. In co-infections with T2 and T4, cleavage in T2 gene 32 by
      T4-encoded SegG initiates a gene conversion event that results in replacement of
      T2 gene 32 markers with the corresponding T4 sequence. Interestingly, segG
      inheritance is limited, apparently because of the physical separation of its
      cleavage and insertion sites, which are 332 base-pairs apart. This contrasts with
      efficient inheritance of the phage T4 td group I intron and its endonuclease, I
      TevI, for which the distance separating the I-TevI cleavage site and td insertion
      site is 23 base-pairs. Furthermore, we show that co-conversion tracts generated
      by repair of SegG and I-TevI double-strand breaks contribute to the localized
      exclusion of T2 markers. Our results demonstrate that the endonuclease activities
      of SegG and I-TevI promote the spread of these two endonucleases to progeny
      phage, consistent with their role as selfish genetic elements, and also provide a
      mechanism by which the genetic contribution of T2 markers to progeny phage is
      reduced.

PMID- 14596797
TI  - Drug recognition and stabilisation of the parallel-stranded DNA quadruplex
      d(TTAGGGT)4 containing the human telomeric repeat.
AB  - The NMR structure of the parallel-stranded DNA quadruplex d(TTAGGGT)(4),
      containing the human telomeric repeat, has been determined in solution in complex
      with a fluorinated pentacyclic quino[4,3,2-kl]acridinium cation (RHPS4). RHPS4
      has been identified as a potent inhibitor of telomerase at submicromolar levels
      (IC(50) value of 0.33(+/-0.13)microM), exhibiting a wide differential between
      telomerase inhibition and acute cellular toxicity. All of the data point to RHPS4
      exerting its chemotherapeutic potency through interaction with, and stabilisation
      of, four-stranded G-quadruplex structures. RHPS4 forms a dynamic interaction with
      d(TTAGGGT)(4), as evident from 1H and 19F linewidths, with fast exchange between
      binding sites induced at 318 K. Perturbations to DNA chemical shifts and 24
      intermolecular nuclear Overhauser effects (NOEs) identify the 5'-ApG and 5'-GpT
      steps as the principle intercalation sites; a structural model has been refined
      using NOE-restrained molecular dynamics. The central G-tetrad core remains
      intact, with drug molecules stacking at the ends of the G-quadruplex. The partial
      positive charge on position 13-N of the acridine ring appears to act as a
      "pseudo" potassium ion and is positioned above the centre of the G-tetrad in the
      region of high negative charge density. In both ApG and GpT intercalation sites,
      the drug is seen to converge to the same orientation in which the pi-system of
      the drug overlaps primarily with two bases of each G-tetrad. The drug is held in
      place by stacking interactions with the G-tetrads; however, there is some
      evidence for a more dynamic, weakly stabilised A-tetrad that stacks partially on
      top of the drug at the 5'-end of the sequence. Together, the interactions of
      RHPS4 increase the t(m) of the quadruplex by approximately 20 degrees C. There is
      no evidence for drug intercalation within the G-quadruplex; however, the
      structural model strongly supports end-stacking interactions with the terminal G
      tetrads.

PMID- 14596798
TI  - Defining the bacteriophage T4 DNA packaging machine: evidence for a C-terminal
      DNA cleavage domain in the large terminase/packaging protein gp17.
AB  - Double-stranded DNA packaging in bacteriophage T4 and other viruses occurs by
      translocation of DNA into an empty prohead by a packaging machine assembled at
      the portal vertex. Coordinated with this complex process is the cutting of
      concatemeric DNA to initiate and terminate DNA packaging and encapsidate one
      genome-length viral DNA. The catalytic site responsible for cutting, and the
      mechanisms by which cutting is precisely coordinated with DNA translocation
      remained as interesting open questions. Phage T4, unlike the phages with defined
      ends (e.g. lambda, T3, T7), packages DNA in a strictly headful manner, and
      exhibits no strict sequence specificity to initiate or terminate DNA packaging.
      Previous evidence suggests that the large terminase protein gp17, a key component
      of the T4 packaging machine, possesses a non-specific DNA cutting activity. A
      histidine-rich metal-binding motif, H382-X(2)-H385-X(16)-C402-X(8)-H411-X(2)-H414
      X(15)-H430-X(5)-H436, in the C-terminal half of gp17 is thought to be involved in
      the terminase cleavage. Here, exhaustive site-directed mutagenesis revealed that
      none of the cysteine and histidine residues other than the H436 residue is
      critical for function. On the other hand, a cluster of conserved residues within
      this region, D401, E404, G405, and D409, are found to be critical for function.
      Biochemical analyses showed that the D401 mutants exhibited a novel phenotype,
      showing a loss of in vivo DNA cutting activity but not the DNA packaging
      activity. The functional nature of the critical residues and their disposition in
      the conserved loop region between two predicted beta-strands suggest that these
      residues are part of a metal-coordinated catalytic site that cleaves the
      phosphodiester bond of DNA substrate. The data suggest that the T4 terminase
      consists of at least two functional domains, an N-terminal DNA-translocating
      ATPase domain and a C-terminal DNA-cutting domain. Although the DNA recognition
      mechanisms may be distinct, it appears that T4 and other phage terminases employ
      a common catalytic paradigm for phosphodiester bond cleavage that is used by
      numerous nucleases.

PMID- 14596799
TI  - "Antiparallel" DNA loop in gal repressosome visualized by atomic force
      microscopy.
AB  - DNA looping is often involved in positive and negative regulation of gene
      transcription in both prokaryotes and eukaryotes. The transcription of the gal
      operon of Escherichia coli from two overlapping promoters P1 and P2 is negatively
      regulated via Gal repressosome assembly. It involves binding of two dimeric Gal
      repressor proteins (GalR) to two operators, O(E) and O(I), flanking the two
      promoters, and formation of 113 bp DNA loop due to tetramerization of the two
      bound GalR dimers. The process requires negatively supercoiled DNA and the
      presence of the histone-like protein HU. Previous modeling of the repressosome
      based on evaluation of DNA elastic energy suggested a mutual antiparallel, rather
      than parallel, orientation of the two gal operators in an under-twisted DNA loop.
      To visualize the Gal loop by atomic force microscopy (AFM), plasmid DNA molecules
      were constructed with increased distance between the two operators. The AFM
      results demonstrated the formation of an antiparallel DNA loop in the Gal
      repressosome consistent with our earlier hypothesis. Importantly, the overall
      shape of the GalR mediated loop proved to be indistinguishable from that in the
      chimerical loop of the same size containing two lac operators (instead of two gal
      operators) and formed by LacI. In addition, a possibility of the gal operon
      repression mediated by GalR in the absence of HU was shown in the new DNA
      constructs. Implications of these findings for the DNA structural organization in
      bacterial nucleoid are discussed.

PMID- 14596800
TI  - Calcium supports loop closure but not catalysis in Rubisco.
AB  - Rubisco (ribulose-1,5-bisphosphate carboxylase/oxygenase) catalyses CO(2)
      assimilation in biology. A prerequisite for catalysis is an activation process,
      whereby an active site lysine is selectively carbamylated. The carbamyl group is
      then stablised by a metal ion, which in vivo is Mg(2+). Other divalent metal ions
      can replace Mg(2+) as activators in vitro, but the nature of the metal ion
      strongly influences the catalytic activity of the enzyme and has a differential
      effect on the ratio of the carboxylation reaction and the competing oxygenation
      reaction. Biochemical studies show that calcium promotes carbamylation but not
      catalysis. To investigate the role of the metal in catalysis, we have determined
      two structures of the enzyme complexed with Ca(2+) and the transition state
      analogue 2-carboxy-D-arbinitol-1,5-bisphosphate (2CABP). One of the complexes was
      prepared by soaking 2CABP into crystals of the enzyme-Ca(2+)-product complex,
      while the other was obtained by cocrystallising the enzyme with calcium and 2CABP
      under activating conditions. The two crystals belong to different space groups,
      and one was merohedrally twinned. Both complexes show very similar three
      dimensional features. The enzyme is carbamylated at Lys201, and requisite loops
      close over the bound ligands in the active site, shielding them from the solvent
      in a manner similar to the corresponding complex with Mg(2+). However, there are
      subtle differences that could explain the particular role of Ca(2+) in these
      processes. The larger radius of the calcium ion and its reduced Lewis-acid
      character causes a significant increase in the required proton hop distance
      between the C3 proton and the carbamate on Lys201 in the calcium complex. This
      alone could explain the inability of calcium to sustain catalysis in Rubisco.
      Similar effects are also expected on subsequent proton transfer steps in the
      catalytic cycle. Here we also discuss the effect of metal substitution on the
      dynamics of the ligands around the metal ion.

PMID- 14596801
TI  - Mechanical design of the first proximal Ig domain of human cardiac titin revealed
      by single molecule force spectroscopy.
AB  - The elastic I-band part of muscle protein titin contains two tandem
      immunoglobulin (Ig) domain regions of distinct mechanical properties. Until
      recently, the only known structure was that of the I27 module of the distal
      region, whose mechanical properties have been reported in detail. Recently, the
      structure of the first proximal domain, I1, has been resolved at 2.1A. In
      addition to the characteristic beta-sandwich structure of all titin Ig domains,
      the crystal structure of I1 showed an internal disulfide bridge that was proposed
      to modulate its mechanical extensibility in vivo. Here, we use single molecule
      force spectroscopy and protein engineering to examine the mechanical architecture
      of this domain. In contrast to the predictions made from the X-ray crystal
      structure, we find that the formation of a disulfide bridge in I1 is a relatively
      rare event in solution, even under oxidative conditions. Furthermore, our studies
      of the mechanical stability of I1 modules engineered with point mutations reveal
      significant differences between the mechanical unfolding of the I1 and I27
      modules. Our study illustrates the varying mechanical architectures of the titin
      Ig modules.

PMID- 14596802
TI  - The mapping and reconstitution of a conformational discontinuous B-cell epitope
      of HIV-1.
AB  - A method for the discovery of the structure of conformational discontinuous
      epitopes of monoclonal antibodies (mAbs) is described. The mAb is used to select
      specific phages from combinatorial phage-display peptide libraries that in turn
      are used as an epitope-defining database that is applied via a novel computer
      algorithm to analyze the crystalline structure of the original antigen. The
      algorithm is based on the following: (1) Most contacts between a mAb and an
      antigen are through side-chain atoms of the residues. (2) In the three
      dimensional structure of a protein, amino acid residues remote in linear sequence
      can juxtapose to one another through folding. (3) Tandem amino acid residues of
      the selected phage-displayed peptides can represent pairs of juxtaposed amino
      acid residues of the antigen. (4) Contact residues of the epitope are accessible
      to the antigen surface. (5) The most frequent tandem pairs of amino acid residues
      in the selected phage-displayed peptides can reflect pairs of juxtaposed amino
      acid residues of the epitope. Application of the algorithm enabled prediction of
      epitopes. On the basis of these predictions, segments of an antigen were used to
      reconstitute an antigenic epitope mimetic that was recognized by its original
      mAb.

PMID- 14596803
TI  - The remarkable flexibility of the human antibody repertoire; isolation of over
      one thousand different antibodies to a single protein, BLyS.
AB  - It is well established that the humoral immune response can generate antibodies
      to many different antigens. The antibody diversity required to achieve this is
      believed to be substantial. However, the extent to which the immune repertoire
      can generate structural diversity against a single target antigen has never been
      addressed. Here, we have used phage display to demonstrate the extraordinary
      capacity of the human antibody repertoire. Over 1000 antibodies, all different in
      amino acid sequence, were generated to a single protein, B-lymphocyte stimulator
      (BLyS protein). This is a highly diverse panel of antibodies as exemplified by
      the extensive heavy and light chain germline usage: 42/49 functional heavy chain
      germlines and 19/33 V(lambda) and 13/35 V(kappa) light chain germlines were all
      represented in the panel of antibodies. Moreover, a high level of sequence
      diversity was observed in the V(H) CDR3 domains of these antibodies, with 568
      different amino acid sequences identified. Thus we have demonstrated that
      specific recognition of a single antigen can be achieved from many different VDJ
      combinations, illustrating the remarkable problem-solving ability of the human
      immune repertoire. When studied in a biochemical assay, around 500 (40%) of these
      antibodies inhibited the binding of BLyS to its receptors on B-cell lines. The
      most potent antibodies inhibited BLyS binding with sub-nanomolar IC(50) values
      and with sub-nanomolar affinities. Such antibodies provide excellent choices as
      candidates for the treatment of BLyS-associated autoimmune diseases.

PMID- 14596804
TI  - Gelsolin domain 2 Ca2+ affinity determines susceptibility to furin proteolysis
      and familial amyloidosis of finnish type.
AB  - Mutation of aspartic acid 187 to asparagine (D187N) or tyrosine (D187Y) in domain
      2 of the actin-modulating protein gelsolin causes the neurodegenerative disease
      familial amyloidosis of Finnish type (FAF). These mutations render plasma
      gelsolin susceptible to aberrant proteolysis by furin in the trans-Golgi network,
      the initial proteolytic event in the formation of 71 and 53 residue fragments
      that assemble into amyloid fibrils. Ca(2+) binding stabilizes wild-type domain 2
      gelsolin against denaturation and proteolysis, but the FAF variants are unable to
      bind and be stabilized by Ca(2+). Though the chain of events initiating FAF has
      been elucidated recently, uncertainty remains about the mechanistic details that
      allow the FAF variants to be processed. To test the hypothesis that impaired
      Ca(2+) binding in the D187 variants, but not other factors specific to residue
      187, increases susceptibility to aberrant proteolysis and subsequent
      amyloidogenesis, we designed the gelsolin variant E209Q to remove a different
      Ca(2+) ligand from the same Ca(2+) site that is affected in the FAF variants.
      Here, we show that E209Q domain 2 does not bind Ca(2+) and is not stabilized
      against denaturation or furin proteolysis, analogous to the behavior exhibited by
      the FAF variants. Transfection of full-length E209Q into COS cells results in
      secretion of both the full-length and furin-processed fragments, as observed with
      D187N and D187Y. Mutation of the furin consensus sequence in D187N and E209Q
      gelsolin prevents cleavage during secretion, indicating that inhibition of
      proprotein convertases (furin) represents a viable therapeutic approach for the
      treatment of FAF. Mutations that diminish domain 2 Ca(2+) binding allow furin
      access to an otherwise protected cleavage site, initiating the proteolytic
      cascade that leads to gelsolin amyloidogenesis and FAF.

PMID- 14596805
TI  - Protein aggregation and amyloid fibril formation by an SH3 domain probed by
      limited proteolysis.
AB  - The SH3 domains are small protein modules of 60-85 amino acid residues that are
      found in many proteins involved in intracellular signal transduction. The SH3
      domain of the p85alpha subunit of bovine phosphatidylinositol 3'-kinase (PI3-SH3)
      under acidic solution adopts a compact denatured state from which amyloid fibrils
      are readily formed. This aggregation process has been found to be modulated
      substantially by solution conditions. Here, we have analyzed the conformational
      features of the native and acid denatured states of PI3-SH3 by limited
      proteolysis experiments using proteinase K and pepsin, respectively. Moreover, we
      have analyzed the propensity of PI3-SH3 to be hydrolyzed by pepsin at different
      stages in the process of aggregation and amyloid formation at pH 1.2 and 2.0 and
      compared the sites of proteolysis under these conditions with the conformational
      features of both native and aggregated PI3-SH3. The results demonstrate that the
      denatured state of PI3-SH3 formed at low pH is relatively resistant to
      proteolysis, indicating that it is partially folded. The long loop connecting
      beta-strands b and c in the native protein is the region in this structure most
      susceptible to proteolysis. Remarkably, aggregates of PI3-SH3 that are formed
      initially from this denatured state in acid solution display enhanced
      susceptibility to proteolysis of the long loop, suggesting that the protein
      becomes more unfolded in the early stages of aggregation. By contrast, the more
      defined amyloid fibrils that are formed over longer periods of time are
      completely resistant to proteolysis. We suggest that the protein aggregates
      formed initially are relatively dynamic species that are able readily to
      reorganize their interactions to enable formation of very well ordered fibrillar
      structures. In addition, the disordered and non-native character of the
      polypeptide chains in the early aggregates could be important in determining the
      high cytotoxicity that has been revealed in previous studies of these species.

PMID- 14596806
TI  - Structure determination and ligand interactions of the PDZ2b domain of PTP-Bas
      (hPTP1E): splicing-induced modulation of ligand specificity.
AB  - Two versions of the PDZ2 domain of the protein tyrosine phosphatase PTP-Bas/human
      PTP-BL are generated by alternative splicing. The domains differ by the insertion
      of five amino acid residues and their affinity to the tumour suppressor protein
      APC. Whereas PDZ2a is able to bind APC in the nanomolar range, PDZ2b shows no
      apparent interaction with APC. Here the solution structure of the splicing
      variant of PDZ2 with the insertion has been determined using 2D and 3D
      heteronuclear NMR experiments. The structural reason for the changed binding
      specificity is the reorientation of the loop with extra five amino acid residues,
      which folds back onto beta-strands two and three. In addition the side-chain of
      Lys32 closes the binding site of the APC binding protein and the two helices,
      especially alpha-helix 2, change their relative position to the protein core.
      Consecutively, the binding site is sterically no longer fully accessible. From
      the NMR-titration studies with a C-terminal APC-peptide the affinity of the
      peptide with the protein can be estimated as 540(+/-40)microM. The binding site
      encompasses part of the analogous binding site of PDZ2a as already described
      previously, yet specific interaction sites are abolished by the insertion of
      amino acids in PDZ2b. As shown by high-affinity chromatography, GST-PDZ2b and GST
      PDZ2a bind to phosphatidylinositol 4,5-bisphosphate (PIP(2)) micelles with a
      dissociation constant K(D) of 21 microM and 55 microM, respectively. In line with
      these data PDZ2b binds isolated, dissolved PIP(2) and PIP(3)
      (phosphatidylinositol 3,4,5-trisphosphate) molecules specifically with a lower
      K(D) of 230(+/-20)microM as detected by NMR spectroscopy. The binding site could
      be located by our studies and involves the residues Ile24, Val26, Val70, Asn71,
      Gly77, Ala78, Glu85, Arg88, Gly91 and Gln92. PIP(2) and PIP(3) binding takes
      place in the groove of the PDZ domain that is normally part of the APC binding
      site.

PMID- 14596807
TI  - Parameterization and classification of the protein universe via geometric
      techniques.
AB  - We present a scheme for the classification of 3487 non-redundant protein
      structures into 1207 non-hierarchical clusters by using recurring structural
      patterns of three to six amino acids as keys of classification. This results in
      several signature patterns, which seem to decide membership of a protein in a
      functional category. The patterns provide clues to the key residues involved in
      functional sites as well as in protein-protein interaction. The discovered
      patterns include a "glutamate double bridge" of superoxide dismutase, the
      functional interface of the serine protease and inhibitor, interface of
      homo/hetero dimers, and functional sites of several enzyme families. We use
      geometric invariants to decide superimposability of structural patterns. This
      allows the parameterization of patterns and discovery of recurring patterns via
      clustering. The geometric invariant-based approach eliminates the computationally
      explosive step of pair-wise comparison of structures. The results provide a vast
      resource for the biologists for experimental validation of the proposed
      functional sites, and for the design of synthetic enzymes, inhibitors and drugs.

PMID- 14596809
TI  - The orexin/hypocretin system: a critical regulator of neuroendocrine and
      autonomic function.
AB  - The hypocretins/orexins are hypothalamic peptides most recognized for their
      significant effects on feeding and arousal. Indeed, loss of the peptides results
      in a cataplexy quite similar to that observed canine models of human narcolepsy.
      However, neurons producing these peptides project to numerous brain sites known
      to be important in neuroendocrine regulation of pituitary function and autonomic
      centers as well. Results from numerous laboratories have suggested broad
      physiological roles for the hypocretins/orexins in neuroendocrine and autonomic
      regulation as a consequence of actions in the dorsal vagal complex,
      paraventricular nucleus, and pituitary. This review focuses upon evidence for
      potential physiologic roles for the peptides in these sites.

PMID- 14596810
TI  - Central mechanisms of stress integration: hierarchical circuitry controlling
      hypothalamo-pituitary-adrenocortical responsiveness.
AB  - Appropriate regulatory control of the hypothalamo-pituitary-adrenocortical stress
      axis is essential to health and survival. The following review documents the
      principle extrinsic and intrinsic mechanisms responsible for regulating stress
      responsive CRH neurons of the hypothalamic paraventricular nucleus, which summate
      excitatory and inhibitory inputs into a net secretory signal at the pituitary
      gland. Regions that directly innervate these neurons are primed to relay sensory
      information, including visceral afferents, nociceptors and circumventricular
      organs, thereby promoting 'reactive' corticosteroid responses to emergent
      homeostatic challenges. Indirect inputs from the limbic-associated structures are
      capable of activating these same cells in the absence of frank physiological
      challenges; such 'anticipatory' signals regulate glucocorticoid release under
      conditions in which physical challenges may be predicted, either by innate
      programs or conditioned stimuli. Importantly, 'anticipatory' circuits are
      integrated with neural pathways subserving 'reactive' responses at multiple
      levels. The resultant hierarchical organization of stress-responsive
      neurocircuitries is capable of comparing information from multiple limbic sources
      with internally generated and peripherally sensed information, thereby tuning the
      relative activity of the adrenal cortex. Imbalances among these limbic pathways
      and homeostatic sensors are likely to underlie hypothalamo-pituitary
      adrenocortical dysfunction associated with numerous disease processes.

PMID- 14596811
TI  - Structure of the GnRH receptor-stimulated signaling network: insights from
      genomics.
AB  - The GnRH receptor influences gene expression in the gonadotrope through
      activating signaling cascades that modulate transcription factor expression and
      activity. A longstanding question in neuroendocrinology is how instructions
      received at the membrane in the form of the pattern of receptor stimulation are
      processed into specific biosynthetic changes at each gonadotropin promoter.
      Signal transduction from the membrane to preformed transcription factors relies
      on recognition of altered conformations. Signal transduction through the layers
      of the gene network also requires the biosynthesis of new transcription factors.
      The signal processing of this system depends on its molecular connectivity map
      and its feedback and feed-forward loops. Review of signal transduction, gene
      control, and genomic studies provide evidence of key loops that cross between
      cellular and nuclear compartments. Genomic studies suggest that the signal
      transduction and gene network form a continuum. We propose that information
      transfer in the gonadotrope depends on robust signaling modules that serve to
      integrate events at different time scales across cytoplasmic and nuclear
      compartments.

PMID- 14596812
TI  - Nutritional status in the neuroendocrine control of growth hormone secretion: the
      model of anorexia nervosa.
AB  - Growth hormone (GH) plays a key role not only in the promotion of linear growth
      but also in the regulation of intermediary metabolism, body composition, and
      energy expenditure. On the whole, the hormone appears to direct fuel metabolism
      towards the preferential oxidation of lipids instead of glucose and proteins, and
      to convey the energy derived from metabolic processes towards the synthesis of
      proteins. On the other hand, body energy stores and circulating energetic
      substrates take an important part in the regulation of somatotropin release.
      Finally, central and peripheral peptides participating in the control of food
      intake and energy expenditure (neuropeptide Y, leptin, and ghrelin) are also
      involved in the regulation of GH secretion. Altogether, nutritional status has to
      be regarded as a major determinant in the regulation of the somatotropin
      somatomedin axis in animals and humans. In these latter, overweight is associated
      with marked impairment of spontaneous and stimulated GH release, while acute
      dietary restriction and chronic undernutrition induce an amplification of
      spontaneous secretion together with a clear-cut decrease in insulin-like growth
      factor I (IGF-I) plasma levels. Thus, over- and undernutrition represent two
      conditions connoted by GH hypersensitivity and GH resistance, respectively.
      Anorexia nervosa (AN) is a psychiatric disorder characterized by peculiar changes
      of the GH-IGF-I axis. In these patients, low circulating IGF-I levels are
      associated with enhanced GH production rate, highly disordered mode of
      somatotropin release, and variability of GH responsiveness to different
      pharmacological challenges. These abnormalities are likely due not only to the
      lack of negative IGF-I feedback, but also to a primary hypothalamic alteration
      with increased frequency of growth hormone releasing hormone discharges and
      decreased somatostatinergic tone. Given the reversal of the above alterations
      following weight recovery, these abnormalities can be seen as secondary, and
      possibly adaptive, to nutritional deprivation. The model of AN may provide
      important insights into the pathophysiology of GH secretion, in particular as
      regards the mechanisms whereby nutritional status effects its regulation.

PMID- 14596813
TI  - Analysis of the transforming growth factor-beta1 (TGF-beta1) codon 25 gene
      polymorphism by LightCycler-analysis in patients with chronic hepatitis C
      infection.
AB  - The polymorphism at position 25 of the gene encoding transforming growth factor
      beta1 (TGF-beta1), which changes the amino acid sequence of the signal peptide
      sequence (arginine to proline), is causing a variation in TGF-beta1 production.
      The homozygous genotype (Arg25Arg) is associated with higher TGF-beta1 production
      than the heterozygous (Arg25Pro) genotype. Therefore, the possible involvement of
      this genetic variation in the TGF-beta1 gene for induction and progression of
      various diseases is under close investigation. At present, several labor
      intensive established assays ranging from amplification refractory mutation
      system (ARMS)-PCR methodologies, sequence specific oligonucleotide probing
      (SSOP), restriction fragment length polymorphism (RFLP) analysis, 5' nuclease
      assays, and specialized fingerprinting protocols are applied to analyze the
      polymorphism in question. We developed a novel approach for analyzing this
      polymorphism in a LightCycler system and determined the allele frequency
      distributions between patients with different degrees of hepatic fibrosis induced
      by chronic hepatitis C virus infection. In patients with severe hepatic fibrosis
      (METAVIR-score 3-4), the Pro25 allele was twice as frequent compared to patients
      with mild fibrosis (METAVIR-score 0-2). However, we found no association of
      necroinflammatory activity and genotype distribution. This suggests that the
      stage of hepatic fibrosis, rather than the grade (inflammation), is influenced by
      the presence of proline at codon 25 in patients with chronic hepatitis C.

PMID- 14596814
TI  - Gene expression of transforming growth factor beta receptors I and II in non
      small-cell lung tumors.
AB  - Transforming growth factor (TGF)beta inhibits normal epithelial cell
      proliferation. A decreased expression of TGFbeta receptors (TbetaR) has been
      associated with loss of TGFbeta sensitivity and enhanced tumor progression in
      many types of cancer. Although lung cancer is one of the leading causes of cancer
      death, a comparative analysis of TbetaR mRNA and protein expression in non-small
      cell (NSC) lung tumors has not been performed. Lung tumor tissues and control non
      lesional lung tissues were obtained from 17 patients undergoing thoracotomy for
      primary NSC lung tumors in clinical stage II. Each tissue sample was studied for
      TbetaRI and TbetaRII mRNA and immunoreactive protein expression, using a semi
      quantitative reverse transcription-PCR method, and a quantitative
      immunohistochemistry method, respectively. TbetaRI protein expression was higher
      in tumors than in controls (p=0.0005) and a similar trend was present at the mRNA
      level. TbetaRII protein expression was not significantly different between tumors
      and controls, however an intense peri-nuclear staining for TbetaRII was observed
      in several tumor cells. TbetaRII mRNA levels were lower in tumors than in
      controls (p=0.005) and an inverse relation between TbetaRII mRNA and protein
      expression was detected in tumors (p=0.0013). Our findings suggest an altered
      function of the TbetaR system in NSC lung cancer.

PMID- 14596815
TI  - Quantitative multiplex real-time PCR for the sensitive detection of interferon
      beta gene induction and viral suppression of interferon beta expression.
AB  - Interferon-beta (IFN-beta) protein and activity can be detected by enzyme
      immunoassays and biological assays. However, precise quantification of low IFN
      beta mRNA concentrations, which is advantageous for investigating IFN-beta gene
      expression in small tissue samples or during the early stage of a virus
      infection, remains a challenge. Therefore, we established a quantitative real
      time PCR (qPCR) for IFN-beta and the housekeeping gene porphobilinogen deanimase
      (PBGD) in separated assays as well as in a multiplex procedure. Sensitivity for
      both the templates was less than 20 copies with an intra- and interassay
      variability of less than 5%. IFN-beta qPCR was utilized to optimize IFN-beta
      induction with dsRNA polyinosic-polycytidylic acid (poly I:C), delivered by a
      liposomal transfection agent for reproducible but low, non-cell-toxic IFN-beta
      concentrations. For studying coxsackievirus B3 (CVB3) interference with IFN-beta
      expression, CVB3 infected fibroblasts were induced with poly I:C. A significant
      reduction of IFN-beta mRNA but not PBGD mRNA was demonstrated 5 h after CVB3
      infection, indicating a specific inhibition of IFN-beta expression by CVB3 on the
      mRNA level, in addition to previously reported effects on the translation/post
      translation level. In conclusion, sensitive IFN-beta/PBGD multiplex qPCR proved
      to be a useful tool to study viral interaction with IFN-beta expression.

PMID- 14596816
TI  - Effect of IFNgamma on caspase-3, Bcl-2 and Bax expression, and apoptosis in
      rabbit placenta.
AB  - The purpose of this study was to determine whether apoptosis in placenta was
      affected by IFNgamma, which can induce abortion, and whether the effect of
      IFNgamma on apoptosis resulted from an intrinsic program of apoptosis, which was
      regulated by Bcl-2 and Bax. DNA fragmentation analysis indicated that cleavage of
      DNA into 180 bp and its polymers were recognized in placenta in control and
      IFNgamma treated groups. Quantitative analysis of low molecular weight fragments
      of DNA revealed a significant increase in cases of 100,000 IU IFNgamma treatment
      compared with those in normal pregnancy (P<0.05). An analysis in situ revealed
      that apoptosis occurred predominantly in syncytiotrophoblast. Expression of Bcl-2
      and Bax in placenta was evaluated by immunoblot analysis and immunohistochemistry
      study. Bcl-2 was expressed predominantly in syncytiotrophoblast, and was not
      expressed in cytotrophoblast of all cases. Whereas Bax was expressed in
      cytotrophoblast, syncytiotrophoblasts were found to be negative for Bax protein
      expression in all cases. Both Bcl-2 and Bax expression was decreased 0.44 fold
      and 0.46 fold by 50,000 IU IFNgamma and 0.41 fold and 0.03 fold by 100,000 IU
      IFNgamma. This resulted in change of a 0.07 fold increase in the Bax:Bcl-2 ratio
      in 50,000 IU IFNgamma treated groups and 0.41 fold increase in 100,000 IU
      IFNgamma treated groups as compared with those in control groups. The difference
      in Bax to Bcl-2 ratio between control and 100,000 IU IFNgamma treated groups was
      significant (P<0.05). The localization of caspase-3, the executioner of
      apoptosis, was detected in some cytotrophoblast and syncytiotrophoblast and
      increased 0.03 fold and 0.68 fold in 50,000 IU IFNgamma and 100,000 IU IFNgamma
      treated groups, respectively. There was significant difference between control
      and 100,000 IU IFNgamma treated groups (P<0.05). The results showed that high
      dose of IFNgamma administration increased the extent of apoptosis in placenta,
      the Bax to Bcl-2 ratio, and the activated caspase-3.

PMID- 14596817
TI  - Cytokine production profile in patients with Behcet's disease treated with
      infliximab.
AB  - Although the etiology of Behcet's disease (BD) still remains uncertain, various
      immune abnormalities have been implicated in BD. We studied cytokine production
      in patients with active and inactive BD, and evaluated the effect of treatment
      with infliximab (anti-TNF-alpha antibody) on disease activity and cytokine
      production by the ELISPOT assay. The numbers of cells spontaneously secreting IFN
      gamma, IL-12, and TNF-alpha were significantly increased in patients with active
      BD. Mitogen-stimulated IL-4 secretion was elevated in active patients, though the
      ratio of IFN-gamma:IL-4 secreting cells was significantly increased in active BD.
      Next, we monitored cytokine production and expression of IL-12 receptor beta1
      chain (IL-12Rbeta1) during short- and long-term infliximab treatment. A single
      infusion of infliximab significantly reduced the number of PBMC secreting TNF
      alpha within 24 h. A rise in TNF-alpha production was associated with clinical
      deterioration. Infliximab treatment induced a significant increase in the number
      of cells secreting IFN-gamma and expressing IL-12Rbeta1. A favorable clinical
      response to infliximab was associated with a persistent reduction in TNF-alpha
      secretion, but did not correlate with IFN-gamma production. Our findings indicate
      that TNF-alpha plays a pivotal role in BD, and that anti-TNF-alpha therapy both
      reduces TNF-alpha production and modulates the functional activity of type 1
      cells.

PMID- 14596818
TI  - Disturbance of pro-inflammatory cytokines in post-traumatic psychopathology.
AB  - BACKGROUND: Post-traumatic psychopathology (PTP) is important to the orthopaedic
      surgeon as it may complicate the recovery from musculoskeletal injury. PTP is
      associated with a disturbance of the hypothalamic-pituitary-adrenal axis, and may
      lead to impaired healing. We have investigated the relationship between PTP and
      pro-inflammatory markers of the metabolic response to trauma. MATERIALS AND
      METHODS: A prospective cohort study of 82 patients with musculoskeletal injuries,
      correlating development of psychopathology (measured by general health
      questionnaire) and pro-inflammatory markers (CRP, IL-6, sIL-6r, TNF-alpha) two
      and six months after their injury. RESULTS: Psychological disturbance was found
      in 39% of patients at two months and 18% at six months. This disturbance was
      associated with significantly increased levels of IL-6 at two months and of sIL
      6r and TNF-alpha at six months. CRP levels were not related to the development of
      PTP. CONCLUSIONS: The relationship between PTP and disturbances of pro
      inflammatory markers needs further exploration, but may explain in part the
      impaired functional recovery when musculoskeletal trauma is complicated by
      psychological disturbance.

PMID- 14596819
TI  - Increased expression of CD95-ligand and other apoptotic signaling factors by
      fumonisin B1, a hepatotoxic mycotoxin, in livers of mice lacking tumor necrosis
      factor alpha.
AB  - Fumonisin B1 (FB1), a mycotoxin, is a potent inhibitor of ceramide synthase, and
      produces organ-, species-, and even gender-specific toxic responses in animals.
      The hepatotoxic response of FB1 in mice involves accumulation of free sphingoid
      bases and induction of inflammatory cytokines including tumor necrosis factor
      alpha (TNFalpha). The FB1-induced hepatotoxic responses were reduced in mice
      lacking TNFalpha receptor (TNFR) 1 or TNFR2. However, the hepatotoxicity was
      exacerbated in mice lacking TNFalpha. We therefore investigated the modulation of
      various other apoptotic signaling factors in TNFalpha-knockout (TKO) mice
      compared to wild-type (WT) strain after repeated daily subcutaneous injections of
      2.25 mg/kg FB1 treatment for 5 days. Expression of various signaling genes in
      liver was evaluated by ribonuclease protection assay. Expression of CD95-ligand
      (FasL) was more than doubled in TKO animals after FB1 whereas it was unaltered in
      the WT group. FB1 did not alter CD95 expression in either strain; however,
      expressions of TRAIL, and downstream signaling factors FADD, TRADD, and caspase 8
      were higher in FB1-treated TKO mice than in the corresponding WT animals. The TKO
      strain had a higher constitutive expression of apoptotic factors except CD95L. In
      addition to the CD95 and TNFalpha systems, the expression of apoptotic molecules
      bcl-2, b-myc, c-myc, bax, max, mad and IL1alpha was induced by FB1 in TKO mice to
      a greater extent than in WT animals; many of these factors also had a higher
      constitutive expression in TKO animals than WT mice. Results indicated that FB1
      can induce CD95 modulated signaling when TNFalpha is absent. Differential
      constitutive expression of apoptotic genes in TKO mice may explain their
      increased sensitivity to FB1. These results are important in characterizing the
      modulating effect of TNFalpha on apoptotic signaling and in explaining the
      unexpected sensitivity of mice lacking this cytokine in response to hepatotoxic
      xenobiotics.

PMID- 14596820
TI  - A nonradioactive 96-well plate assay for screening of trans-sialidase activity.
AB  - Trans-sialidase (E.C. 3.2.1.18) catalyzes the transfer of preferably alpha2,3
      linked sialic acid to another glycan or glycoconjugate, forming a new alpha2,3
      linkage to galactose or N-acetylgalactosamine. Here, we describe a nonradioactive
      96-well plate fluorescence test for monitoring trans-sialidase activity with high
      sensitivity, specificity, and reproducibility using sialyllactose and 4
      methylumbelliferyl-beta-D-galactoside as donor and acceptor substrates,
      respectively. The assay conditions were optimized using the trans-sialidase from
      Trypanosoma congolense and its general applicability was confirmed with
      recombinant trans-sialidase from Trypanosoma cruzi. Using this procedure, a large
      number of samples can be tested quickly and reliably, for instance in monitoring
      trans-sialidase during enzyme purification and the production of monoclonal
      antibodies, for enzyme characterization, and for identifying potential substrates
      and inhibitors. The trans-sialidase assay reported here was capable of detecting
      trans-sialidase activity in the low-mU range and may be a valuable tool in the
      search for further trans-sialidases in various biological systems.

PMID- 14596821
TI  - A combined oligonucleotide and protein microarray for the codetection of nucleic
      acids and antibodies associated with human immunodeficiency virus, hepatitis B
      virus, and hepatitis C virus infections.
AB  - A multiplexed assay based on the codetection of nucleic acids and antibodies in
      human serum infected by human immunodeficiency virus (HIV), hepatitis B virus
      (HBV) or hepatitis C virus was proposed. The combined immuno- and oligosorbent
      array (CombOLISA) microarray is prepared in 96-well standard microplates by
      spotting (1). nucleic probes specific for a virus genome, (2). viral proteins for
      the capture of serum antibodies, and (3). nonspecific proteins for verifying
      specificity. Experimental assay conditions were optimized so that both DNA
      hybridization and immunological reactions can be achieved simultaneously in the
      same well and buffer and all at the same temperature. A generic detection system
      based on the precipitation of an insoluble colorimetric substrate in the presence
      of enzyme-labeled antibodies or streptavidin was proposed. The optical density of
      each spot was correlated to the corresponding analyte concentration. The
      influence of critical parameters on CombOLISA performance such as serum
      concentration was studied. Calibration curves and sensitivity thresholds were
      established for each parameter. Serial dilutions of serum were correlated to
      results obtained with validated immunoassay platforms such as a microplate enzyme
      linked immunosorbent assay or the VIDAS automat. Also, several HIV- and HBV
      infected serum samples were tested independently by CombOLISA and VIDAS.
      Coefficients of variation for genomic and proteomic parameters vs spot density
      were below 15%.

PMID- 14596822
TI  - Monitoring of the heat-shock response in Escherichia coli using an optical
      biosensor.
AB  - A surface plasmon resonance (SPR) method for monitoring the concentration of the
      chaperone DnaK and its relation to physiological stress response in a recombinant
      Escherichia coli strain subjected to heat shock is described. The DnaK protein,
      an abundantly occurring representative of the heat-shock proteins, was used as a
      marker of physiological stress. The SPR biosensor instrument was used for label
      free immunoaffinity detection directly in cell culture lysates using an anti-DnaK
      monoclonal IgG antibody immobilized on the sensor surface. The SPR method
      provides a fast response (<8 min) and a reproducible (RSD<2%), accurate
      (comparison to the direct enzyme-linked immunosorbent assay), and sensitive
      (LOD<1 nM) assay for determination of the DnaK level in cell culture lysates. The
      operational stability of the method was high compared to that of other SPR
      assays; the sensitivity decreased at only 2.7%/h. This allowed measurement of
      more than 220 samples per sensor surface. Storage stability was determined at 25
      degrees C (100% after 17 h) and 10 degrees C (101% after 1 month). The method was
      validated by standard additions of DnaK (30, 60, and 120 nM) with recovery
      indices in the range 95.7-103.7%.

PMID- 14596823
TI  - Glutathione S-transferase pull-down assays using dehydrated immobilized
      glutathione resin.
AB  - We have developed an affinity-precipitation technique to facilitate conducting
      glutathione S-transferase (GST) pull-down assays. The dehydrated immobilized
      glutathione resin format, when combined with microcentrifuge spin columns, is a
      powerful tool that enables the simultaneous performance of resin hydration, the
      binding of the GST fusion protein, and the pull-down step with the appropriate
      protein partner in a semihigh-throughput fashion (multiple samples processed at
      the same time). The entire assay process is shortened and recovery is enhanced
      when coupled with a spin-column format, providing a convenient way to study
      protein-protein interactions. We successfully tested the resin format/technique
      in three common pull-down applications utilizing radiolabeled, overexpressed, and
      activated endogenous interacting protein partners.

PMID- 14596825
TI  - Microscale synthesis of 2-tritiated isopropanol and 4R-tritiated reduced
      nicotinamide adenine dinucleotide phosphate.
AB  - An improved microscale synthesis of 2-tritiated isopropanol ([2-3H]iPrOH) and R
      tritiated reduced beta-nicotinamide adenine dinucleotide 2(')-phosphate (R-[4
      3H]NADPH) is presented. The current procedure offers high yield, high purity, and
      small-quantity synthesis and is shorter than previous procedures. [2-3H]iPrOH was
      prepared by reduction of acetone with [3H]NaBH(4) under reflux conditions. [2
      3H]iPrOH was used to reduce NADP(+) to R-[4-3H]NADPH with alcohol dehydrogenase
      from Thermoanaerobium brockii at 40 degrees C. This equilibrium reaction was
      drawn toward products by trapping the acetone with an excess of semicarbazide.
      This improvement enables a better control of the reaction time, as the enzymatic
      reduction became rate determining. Greater than 75% of the product was identified
      as reduced cofactor by reverse-phase (RP) HPLC. Longer reaction led to
      decomposition of the product and lower yield. Purification was carried out by
      semipreparative RP HPLC followed by lyophilization and yielded a compound of high
      purity that was preserved at -80 degrees C. Applications of the new procedure to
      a wide variety of specific radioactivities ranging from carrier-free to a few
      Ci/mmol are discussed. The intriguing formation of radioactive NADP(+) by-product
      (the major product in some reported procedures), was also studied and minimized
      in the procedure described below. Finally, the usage of the labeled cofactor is
      demonstrated with the enzymes dihydrofolate reductase and thymidylate synthase.

PMID- 14596824
TI  - High-throughput methods to detect dimerization of Bcl-2 family proteins.
AB  - Members of the Bcl-2 family are critical regulators of apoptosis. Antiapoptotic
      family proteins such as Bcl-2 and Bcl-x(L) function, at least in part, by binding
      proapoptotic members such as Bax and Bak and thereby preventing release of
      apoptotic proteins, including cytochrome c, from the mitochondria. "BH3-only"
      members of the family disrupt this interaction by binding, via their BH3 domain,
      to a hydrophobic pocket on the surface of the antiapoptotic members. Disruption
      of heterodimerizations by small-molecule inhibitors could be used to modulate
      cell death in both cancer (to increase apoptosis) and degenerative disorders (to
      decrease apoptosis), and assays are necessary to screen compound libraries.
      Fluorescence polarization and enzyme-linked immunosorbent assay-based methods to
      detect Bcl-2 protein interactions have been described. Here, two further methods
      that are rapid, "mix and read," homogeneous reactions, insensitive to compound
      autofluorescence, and amenable to high-throughput screening, are described: a
      scintillation proximity assay and a time-resolved fluorescence resonance energy
      transfer assay (HTRF). The assays are designed using tags such that different Bcl
      2 family members or BH3 domain peptides can be readily applied to either format,
      as exemplified by the use here of histidine-tagged Bcl-x(L) and biotinylated BH3
      peptides.

PMID- 14596826
TI  - Detection of submicrogram quantities of Escherichia coli lipopolysaccharides by
      agarose-gel electrophoresis.
AB  - A sensitive agarose-gel electrophoresis method has been developed for the
      visualization of lipopolysaccharide (LPS) samples from several Escherichia coli
      serotypes, such as 026:B6, 055:B5, 0128:B12, 0111:B4, 0127:B8, and K235. This
      method can detect as little as 0.5-6 microg of LPS depending on the serotype by
      treatment of the plates with toluidine blue, and it is able to measure sub
      microgram amounts of samples, approx. 0.05-0.5 microg, when the staining with
      toluidine blue followed by Stains-All procedure is adopted. Treatment of LPS with
      alkali under anhydrous conditions removes the ester-linked fatty acids and the
      phosphate groups of the Lipid A component, producing the detoxified LPS. The
      carbohydrate neutral moiety obtained from the hydrolysate does not migrate during
      electrophoresis. This was utilized to monitor quantitatively the removal process
      of the Lipid A component for the formation of the detoxified LPS.

PMID- 14596827
TI  - A general method for the chemical synthesis of gamma-32P-labeled or unlabeled
      nucleoside 5(')-triphosphates and thiamine triphosphate.
AB  - Several methods for the chemical synthesis of gamma-32P-labeled and unlabeled
      nucleoside 5(')-triphosphates and thiamine triphosphate (ThTP) have been
      described. They often proved unsatisfactory because of low yield, requirement for
      anhydrous solvents, procedures involving several steps or insufficient specific
      radioactivity of the labeled triphosphate. In the method described here, all
      these drawbacks are avoided. The synthesis of [gamma-32P]ThTP was carried out in
      one step, using 1,3-dicyclohexyl carbodiimide as condensing agent for thiamine
      diphosphate and phosphoric acid in a dimethyl sulfoxide/pyridine solvent mixture.
      Anhydrous solvents were not required and the yield reached 90%. After
      purification, [gamma-32P]ThTP had a specific radioactivity of 11Ci/mmol and was
      suitable for protein phosphorylation. The method can also be used for the
      synthesis of [gamma-32P]ATP of the desired specific radioactivity. It can easily
      be applied to the synthesis of unlabeled ThTP or ribo- and deoxyribonucleoside
      5(')-triphosphates. In the latter case, inexpensive 5(')-monophosphate precursors
      can be used as reactants in a 20-fold excess of phosphoric acid.
      Deoxyribonucleoside 5(')-triphosphates were obtained in 6h with a yield of at
      least 70%. After purification, the nucleotides were found to be suitable
      substrates for Taq polymerase during polymerase chain reaction cycling. Our
      method can easily be scaled up for industrial synthesis of a variety of labeled
      and unlabeled triphosphoric derivatives from their mono- or diphosphate
      precursors.

PMID- 14596828
TI  - Characterization and application of Raman labels for confocal Raman
      microspectroscopic detection of cellular proteins in single cells.
AB  - A method using confocal Raman microspectroscopy for the detection of cellular
      proteins in single intact cells was developed. Two approaches were used to
      improve the detection of these cellular components. First, compounds with high
      Raman scattering were investigated for potential use as Raman labels. Raman
      labels were conjugated to either biomolecules or biotin and used as markers in
      the detection of cellular enzymes and receptors. Second, silver colloids were
      used to increase the surface-enhanced Raman scatter (SERS) of these Raman labels.
      Cresyl violet and dimethylaminoazobenzene are Raman labels that provide very
      sensitive SERS detection by a confocal Raman microscope with a HeNe laser at
      wavelength of 632.8 nm. The detection of 12-lipoxygenase and cyclooxygenase-1 in
      single bovine coronary artery endothelial cells and the binding of angiotensin II
      to its receptors in zona glomerulosa cells was demonstrated.

PMID- 14596829
TI  - Measuring enzymatic activity of a recombinant amidase using Fourier transform
      infrared spectroscopy.
AB  - A method based on Fourier transform infrared spectroscopy (FT-IR) has been
      developed for assaying the Pseudomonas aeruginosa native amidase (E.C. 3.5.1.4),
      overproduced in an Escherichia coli strain. The kinetic of acetamide hydrolysis
      by the enzyme, in aqueous media, was monitored by measuring the intensity of the
      acetamide amide I band maximum at 1635 cm(-1) as a function of time. A value of
      0.5mM(-1) cm(-1) was obtained for the extinction coefficient (epsilon) of
      acetamide at this frequency. The rate of the hydrolysis was found to be linear
      with the concentration of the enzyme up to 90 microM. The Michaelis-Menten
      kinetics parameters V and K(m) were determined as 30.7 U/mg and 4mM,
      respectively. These results were similar to those obtained using high-performance
      liquid chromatography analysis of the same hydrolytic reaction catalyzed by
      amidase either in water or in buffer. This suggests that the precision of the FT
      IR method is suitable for the kinetic studies of amidase with the additional
      advantage of being able to perform a real-time measurement of the enzymatic
      activity.

PMID- 14596830
TI  - A new approach for the detection of multiple protein kinases using monoclonal
      antibodies directed to the highly conserved region of protein kinases.
AB  - To explore the protein kinase family enzymes expressed in cells, we attempted to
      generate antibodies that could detect a wide variety of protein kinases. For the
      production of such antibodies, synthetic peptides corresponding to amino acid
      sequences of a highly conserved subdomain (subdomain VIB) of the protein kinase
      family were used for immunization. Among the various peptide antigens, a peptide
      with 16 amino acids, CVVHRDLKPENLLLAS, effectively produced polyclonal antibodies
      with broad cross-reactivities to protein kinases. Two monoclonal antibodies,
      designated M8C and M1C, detected a variety of protein kinases such as calmodulin
      dependent protein kinase II, calmodulin-dependent protein kinase IV, cAMP
      dependent protein kinase, and mitogen-activated protein kinases, on Western
      blotting. The antibodies also immunoprecipitated various protein kinases in cell
      extracts. Furthermore, these antibodies could be used for detection of positive
      clones in the expression cloning of various protein kinases. Among 39 positive
      clones obtained from mouse brain cDNA library, 36 clones were identified as cDNA
      clones for various known and novel protein serine/threonine kinases, suggesting
      that the antibodies reacted highly specifically with various protein kinases.
      These results indicate that the present monoclonal antibodies directed to
      multiple protein kinases will be a powerful tool for the detection of a variety
      of known and novel protein kinases in cells.

PMID- 14596831
TI  - Cellodextrin preparation by mixed-acid hydrolysis and chromatographic separation.
AB  - A procedure for preparation of purified cellodextrins in gram quantities was
      developed for use in biochemical and microbiological studies. Cellodextrins were
      prepared by hydrolyzing microcrystalline cellulose (Avicel) over a period of 4 to
      5.5h in the presence of a mixture of 80% (v/v) concentrated hydrochloric acid (
      approximately 37 wt.%) and 20% (v/v) concentrated sulfuric acid ( approximately
      98 wt.%) at room temperature (22 degrees C). Acetone precipitation, washing ion
      exchange, and neutralization with barium hydroxide were used to generate a
      solution of mixed cellodextrins substantially free of acids and salts. Yields
      following hydrolysis and precipitation were approximately 0.05, approximately
      0.07, approximately 0.06, and approximately 0.02 g/g cellulose for cellotriose
      (G(3)), cellotetraose (G(4)), cellopentose (G(5)), and cellohexose (G(6)),
      respectively. Cellodextrins with degrees of polymerization from 3 to 11 were
      separated chromatographically using a 29 x 5-cm I.D. Bio-Rad AG50W-X4 column
      arranged in series with a 91 x 5-cm I.D. Bio-Gel P4 column. This two-column
      system was used to obtain cellodextrin preparations at 240 mg/day for G(3), 330
      mg/day for G(4), 260 mg/day for G(5), and 130 mg/day for G(6), with purity >99%
      for G(3), G(4), and G(5) and >95% for G(6). The overall procedure achieves yields
      comparable to the highest previously reported, employs a separation system that
      can readily be reused for multiple runs, and avoids use of fuming HCl.

PMID- 14596832
TI  - Enzymatic synthesis of radiolabeled phosphonoacetaldehyde.
AB  - Phosphonoacetaldehyde (Pald) is formed in a variety of biosynthetic pathways
      leading to natural phosphonates and is an intermediate in the degradation pathway
      of the natural product 2-aminoethylphosphonate. To facilitate the investigation
      of the enzymes catalyzing these pathways, a method for the synthesis of
      radiolabeled Pald was developed. The enzyme pyruvate phosphate dikinase was used
      to prepare phosphoenolpyruvate (PEP) from pyruvate, adenosine triphosphate (ATP),
      and orthophosphate. Then PEP was converted to phosphonopyruvate (Ppyr) with PEP
      mutase and then to Pald with Ppyr decarboxylase. By using [beta-32P]ATP or [2
      14C]pyruvate as precursor, [32P]Pald or [1-14C]Pald was obtained, respectively.
      The utilization of the synthetic, radiolabeled Pald as a probe of enzyme
      mechanism was demonstrated with the enzyme phosphonoacetaldehyde hydrolase
      (trivial name phosphonatase). The single turnover time course for the formation
      and consumption of radiolabeled covalent enzyme species evidenced a kinetically
      competent covalent intermediate.

PMID- 14596833
TI  - A reagent less fluorescent sol-gel biosensor for uric acid detection in
      biological fluids.
AB  - The simultaneous encapsulation of a coupled uricase-peroxidase system and amplex
      red in a sol-gel matrix allows one to obtain a reagent-less and ready-to-use
      fluorescent biosensor for the accurate detection of uric acid in highly diluted
      biological fluids. The detection limit of the prepared biosensor was found to be
      20 nM and was linear up to 1 microM. The high sensitivity found for the biosensor
      permitted a reliable determination of uric acid concentrations in the presence of
      interfering species (e.g., ascorbic acid) just by sample dilution (up to 50000
      for urine and 10000 for serum and blood). The sol-gel encapsulation preserved the
      hierarchy of the enzyme activity as demonstrated by the performance of the
      fluorescent biosensor.

PMID- 14596834
TI  - Detection and quantitation of fatty acid acyl conjugates of triamcinolone
      acetonide via gas chromatography-electron-capture negative-ion mass spectrometry.
AB  - The inherent electron-capture properties of triamcinolone acetonide (TAA) fatty
      acid conjugates were exploited for development of a GC-MS technique for
      quantitation of C21 long-chain fatty esters of TAA synthesized in BEAS-2B cells,
      an immortalized airway epithelium cell line. TAA esters extracted from BEAS-2B
      cells were purified and detected via selected ion monitoring of the molecular
      anions generated from the TAA esters under electron-capture negative-ion mass
      spectrometric conditions. Standard curves were linear over a range of 0.0 to >4.5
      ng/mg protein with r(2) values = 1. Levels of TAA conjugates extracted from BEAS
      2B treated with 10(-5)M TAA for 24h ranged from 0.024 to 0.301 ng/mg protein.
      Further evidence for confirmation of the identity of TAA fatty esters formed in
      BEAS-2B cells was obtained via selected reaction monitoring. The transition
      monitored was formation of the carboxy anion generated from each of the
      respective molecular anions of the TAA esters during collision-induced
      decomposition. These findings indicate that the GC-MS analysis is suitable for
      studies of the kinetics of the TAA fatty acid conjugates formation in vitro and
      may be directly applicable to determination of the kinetics of TAA fatty acid
      conjugation in vivo.

PMID- 14596835
TI  - An immunoassay for atrazine using tunable immunosorbent.
AB  - A novel, simple, economical, and environmentally friendly tunable immunosorbent
      based immunoassay for sensitive and selective determination of atrazine is
      reported. Tunable immunosorbents consisting of a fusion between an elastin-like
      polypeptide made up of 77 repeating units of the pentapeptide VPGVG and a single
      chain Fv of an anti-atrazine antibody were synthesized biologically and purified
      by temperature-triggered phase transition. A competitive immunoassay based on the
      competition of atrazine-horseradish peroxidase and atrazine was established with
      IC(50) and lower detection limit of 0.16 and 0.01 ppb, respectively. Excellent
      recoveries (mean values ranging between 92 and 104%) were demonstrated in
      simulated atrazine-contaminated water samples.

PMID- 14596836
TI  - A fluorimetric Morgan-Elson assay method for hyaluronidase activity.
AB  - Despite their physiological importance, hyaluronidases (HAases) have long been
      "neglected enzymes," due, presumably, in part to the lack of rapid, sensitive
      assays. Currently, the colorimetric Morgan-Elson assay method, which is based
      upon the generation of a new reducing N-acetyl-D-glucosamine terminus with each
      cleavage reaction, is most widely employed but is yet insensitive. We, therefore,
      reinvestigated the colorimetric method and established the fluorimetric Morgan
      Elson assay for HAase activity, with the optimized tetraborate reagent. The
      fluorimetric assay, requiring neither specialized reagents nor a long time to
      perform, provided high sensitivity, nearly comparable to that of enzyme-linked
      immunosorbent assay (ELISA)-like assays, with a detection limit of 5 x 10(
      3)NFU/ml of bovine testicular HAase after 1-h incubation. The increased
      sensitivity permitted rapid measurement of low HAase activity in biological
      samples such as human and rabbit serum HAases, the latter of which has not been
      detected either by an ELISA-like assay or by zymography. Human serum HAase was
      easily characterized it along with its optimum pH and kinetic parameters.

PMID- 14596837
TI  - Measurement of diacylglycerol acyltransferase activity in isolated hepatocytes.
AB  - An assay procedure for diacylglycerol acyltransferase that allows rapid
      measurement of the activity of this enzyme in isolated hepatocytes is described.
      The one-step procedure involves permeabilization of the plasma membrane with
      digitonin and simultaneous measurement of diacylglycerol acyltransferase
      activity. Digitonin at a concentration of 64 microg/mg of cellular protein was
      found to be optimal for exposing microsomal diacylglycerol acyltransferase to the
      components of the assay. The enzyme assay is linear with time up to 4 min and
      with protein concentrations in the range 0.25-2.4 mg of cellular protein/assay.
      It is shown that there is a good correlation of cellular enzyme activity as
      determined in digitonin-permeabilized hepatocytes with the rate of
      triacylglycerol synthesis in intact hepatocytes.

PMID- 14596838
TI  - Selective labeling and detection of specific mRNA in a total-RNA sample.
AB  - We report a unique approach to selectively label and detect specific RNA using
      its internal sequence, without separation, reverse transcription, and/or
      polymerase chain reaction. This approach is especially useful for individual mRNA
      labeling and detection. To expose mRNA internal sequence for selective labeling
      and detection, RNase H digestion is used to remove the 3(')-common sequences. We
      have designed a DNA-2(')-O-Me-RNA hybrid as the template for both RNase H
      digestion and Klenow extension and have found buffer conditions for both enzymes.
      Sharing the same template and buffer by these two enzymes largely simplifies
      experimental procedures. Using this approach, lacZ mRNA was selectively labeled
      and detected in the presence of thousands of mRNAs. We have successfully
      demonstrated for the first time the direct labeling and detection of an
      individual mRNA in a total-RNA sample. The detection sensitivity can reach up to
      attomole level (5 x 10(-18)mole). This method has great potential in RNA decay
      and metabolic regulation studies via individual mRNA labeling and in methodology
      of mRNA direct detection on microchip and direct gene expression profiling,
      without reverse transcription and polymerase chain reactions.

PMID- 14596839
TI  - Antibiotic interference in protein assays: comparative evaluation of six
      photometric methods.

PMID- 14596840
TI  - The influence of size on the thermal stability of oligonucleotides: the case of
      AT sequences.

PMID- 14596841
TI  - Use of citrate to minimize neutrophil matrix metalloproteinase-9 in human plasma.

PMID- 14596842
TI  - A real-time polymerase chain reaction-based evaluation of cDNA synthesis priming
      methods.

PMID- 14596843
TI  - Effect of blockade of corticotropin-releasing factor receptors in the median
      raphe nucleus on stress-induced c-fos mRNA in the rat brain.
AB  - Using a rat relapse model, we have shown that infusion of a corticotropin
      releasing factor (CRF) receptor antagonist into the median raphe nucleus (MRN)
      blocks footshock stress-induced reinstatement of alcohol seeking in rats. The
      goal of the present study was to begin identifying brain sites potentially
      involved in this effect. For this purpose, we measured levels of c-fos mRNA in
      discrete nuclei of the rat brain following exposure to intermittent footshock,
      which was preceded by intra-MRN infusions of a CRF receptor antagonist, d-Phe CRF
      (0 or 50 ng). Exposure to intermittent footshock increased the expression of c
      fos mRNA in a number of brain regions previously shown to be responsive to
      stressful stimuli. Pretreatment with d-Phe CRF in the MRN selectively attenuated
      the increases in c-fos mRNA induced by footshock in the central nucleus of the
      amygdala (CeA). These findings are consistent with previous data on the important
      role for the CeA in stress-induced reinstatement of drug seeking. These results
      also suggest that inhibition of CeA activity may contribute to the blockade of
      alcohol-seeking induced by footshock that we have observed following injections
      of d-Phe into the MRN.

PMID- 14596844
TI  - Excitatory amino acid receptor activation in the raphe pallidus area mediates
      prostaglandin-evoked thermogenesis.
AB  - To investigate the role of excitatory amino acid neurotransmission within the
      rostral raphe pallidus area (RPa) in thermogenic and cardiovascular responses,
      changes in sympathetic nerve activity to brown adipose tissue (BAT), BAT
      temperature, expired CO(2), arterial pressure, and heart rate were recorded after
      microinjection of excitatory amino acid (EAA) receptor agonists into the RPa in
      urethan-chloralose-anesthetized, ventilated rats. To determine whether EAA
      neurotransmission within the RPa is necessary for the responses evoked by
      disinhibition of the RPa or by prostaglandin E(2) acting within the medial
      preoptic area, BAT sympathetic nerve activity, BAT temperature, expired CO(2),
      arterial pressure, and heart rate were measured during these treatments both
      before and after blockade of EAA receptors within the RPa. Microinjection of EAA
      receptor agonists into the RPa resulted in significant increases in all measured
      variables; these increases were attenuated by prior microinjection of the
      respective EAA receptor antagonists into the RPa. Microinjection of prostaglandin
      E(2) into the medial preoptic area or microinjection of bicuculline into the RPa
      resulted in respective significant increases in BAT sympathetic nerve activity
      (+approximately 190% and +approximately 235% of resting levels), in BAT
      temperature (approximately 1.8 degrees C and approximately 2 degrees C), in
      expired CO(2) (approximately 1.1% and approximately 1.1%), and in heart rate
      (approximately 97 beats per minute (bpm) and approximately 100 bpm). Blockade of
      ionotropic EAA receptors within the RPa by microinjection of kynurenate
      completely reversed the prostaglandin E(2) or bicuculline-evoked increases in all
      of the measured variables. Blockade of either N-methyl-D-aspartate (NMDA)
      receptors or non-NMDA receptors alone resulted in marked attenuations of the
      prostaglandin E(2)-evoked effects on all of the measured variables. These data
      demonstrate that activation of an EAA input to the RPa is necessary for the BAT
      thermogenic and the cardiovascular effects resulting from the actions of
      prostaglandin E(2) within the medial preoptic area or from the disinhibition of
      local neurons in the RPa.

PMID- 14596845
TI  - A diet promoting sugar dependency causes behavioral cross-sensitization to a low
      dose of amphetamine.
AB  - Previous research in this laboratory has shown that a diet of intermittent
      excessive sugar consumption produces a state with neurochemical and behavioral
      similarities to drug dependency. The present study examined whether female rats
      on various regimens of sugar access would show behavioral cross-sensitization to
      a low dose of amphetamine. After a 30-min baseline measure of locomotor activity
      (day 0), animals were maintained on a cyclic diet of 12-h deprivation followed by
      12-h access to 10% sucrose solution and chow pellets (12 h access starting 4 h
      after onset of the dark period) for 21 days. Locomotor activity was measured
      again for 30 min at the beginning of days 1 and 21 of sugar access. Beginning on
      day 22, all rats were maintained on ad libitum chow. Nine days later locomotor
      activity was measured in response to a single low dose of amphetamine (0.5
      mg/kg). The animals that had experienced cyclic sucrose and chow were hyperactive
      in response to amphetamine compared with four control groups (ad libitum 10%
      sucrose and chow followed by amphetamine injection, cyclic chow followed by
      amphetamine injection, ad libitum chow with amphetamine, or cyclic 10% sucrose
      and chow with a saline injection). These results suggest that a diet comprised of
      alternating deprivation and access to a sugar solution and chow produces bingeing
      on sugar that leads to a long lasting state of increased sensitivity to
      amphetamine, possibly due to a lasting alteration in the dopamine system.

PMID- 14596846
TI  - Angiotensin II subtype 1A (AT1A) receptors in the rat sensory vagal complex:
      subcellular localization and association with endogenous angiotensin.
AB  - Angiotensin II (Ang II) type 1 (AT1) receptors are prevalent in the sensory vagal
      complex including the nucleus tractus solitarii (NTS) and area postrema, each of
      which has been implicated in the central cardiovascular effects produced by Ang
      II. In rodents, these actions prominently involve the AT1A receptor. Thus, we
      examined the electron microscopic dual immunolabeling of antisera recognizing the
      AT1A receptor and Ang II to determine interactive sites in the sensory vagal
      complex of rat brain. In both the area postrema and adjacent dorsomedial NTS,
      many somatodendritic profiles were dually labeled for the AT1A receptor and Ang
      II. In these profiles, AT1A receptor-immunoreactivity was often seen in the
      cytoplasm beneath labeled portions of the plasma membrane and in endosome-like
      granules as well as Golgi lamellae and outer nuclear membranes. In addition, AT1A
      receptor labeling was detected on the plasma membrane and in association with
      cytoplasmic membranes in many small axons and axon terminals. These terminals
      were morphologically heterogeneous containing multiple types of vesicles and
      forming either inhibitory- or excitatory-type synapses. In the area postrema,
      AT1A receptor labeling also was detected in many non-neuronal cells including
      glia, capillary endothelial cells and perivascular fibroblasts that were less
      prevalent in the NTS. We conclude that in the rat sensory vagal complex, AT1A
      receptors are strategically positioned for involvement in modulation of the
      postsynaptic excitability and intracrine hormone-like effects of Ang II. In
      addition, these receptors have distributions consistent with diverse roles in
      regulation of transmitter release, regional blood flow and/or vascular
      permeability.

PMID- 14596848
TI  - alpha-Amino-3-hydroxy-5-methyl-isoxazole-4-propionate receptors in spinal cord
      motor neurons are altered in transgenic mice overexpressing human Cu,Zn
      superoxide dismutase (Gly93-->Ala) mutation.
AB  - There are many evidences implicating glutamatergic toxicity as a contributory
      factor in the selective neuronal injury occurring in amyotrophic lateral
      sclerosis (ALS). This neurodegenerative disorder is characterized by the
      progressive loss of motor neurons, whose pathogenesis is thought to involve
      Ca(2+) influx mediated by alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate
      receptors (AMPARs). In the present study we report alterations in the AMPARs
      function in a transgenic mouse-model of the human SOD1(G93A) familial ALS.
      Compared with those expressed in motor neurons carrying the human wild type gene,
      AMPAR-gated channels expressed in motor neurons carrying the human mutant gene
      exhibited modified permeability, altered agonist cooperativity between the sites
      involved in the process of channel opening and were responsible for slower
      spontaneous synaptic events. These observations demonstrate that the SOD1(G93A)
      mutation induces changes in AMPAR functions which may underlie the increased
      vulnerability of motor neurons to glutamatergic excitotoxicity in ALS.

PMID- 14596847
TI  - Expression of Na+/H+ and HCO3- -dependent transporters in Na+/H+ exchanger
      isoform 1 null mutant mouse brain.
AB  - Acid-base transporters, such as the sodium-hydrogen exchangers (NHEs) and
      bicarbonate-dependent transporters, play an important role in the regulation of
      intracellular pH (pH(i)) in the CNS. Previous studies from our laboratory have
      shown that the absence of the major NHE isoform 1 (NHE1) reduced the steady-state
      pH(i) and recovery rate from an acid load in the hippocampal neurons not only in
      HEPES but also in HCO(3)(-) solutions (Yao et al., 1999). The purpose of the
      current study was to determine whether the NHE1 null mutation affects the
      expression of pH-regulatory transporters in the mouse CNS. Immunoblotting and
      semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) were
      performed to examine the protein and mRNA levels of NHE1-4, electrogenic sodium
      bicarbonate cotransporter 1 variants (NBCe1), and brain-specific anion exchanger
      3 (AE3) in four brain regions (cerebral cortex, hippocampus, cerebellum and
      brainstem-diencephalon). NHE1 null mutant mice were compared with their wild type
      controls at the average age of approximately 4 weeks. Our results revealed that
      the NHE1 null mutation caused a significant increase in NHE3 in the cerebellum
      (84% for protein, 105% for mRNA), an increase in NBCe1 expression in the
      brainstem-diencephalon (approximately 40-50% for protein, 9-15% for mRNA), as
      well as a decrease in AE3 in the hippocampus (approximately 60% for protein, 24%
      for mRNA). We conclude that the NHE1 null mutation does alter the expression of
      other membrane transporters at both protein and mRNA levels. The alteration is
      region-specific. An increase in acid extruders (e.g. NHE3) and a decrease in acid
      loaders (e.g. AE3) suggest that there are some compensatory mechanisms that occur
      in NHE1 null mutant mice.

PMID- 14596849
TI  - Tetanus neurotoxin-insensitive vesicle-associated membrane protein localizes to a
      presynaptic membrane compartment in selected terminal subsets of the rat brain.
AB  - Tetanus neurotoxin-insensitive vesicle-associated membrane protein (TI-VAMP) is a
      vesicular soluble N-ethyl maleimide-sensitive fusion protein attachment protein
      receptor (SNARE) that has been implicated in neurite outgrowth. It has previously
      been reported that TI-VAMP is localised in the somatodendritic compartment of
      neurons indicating a role in membrane fusion events within dendrites. Using a
      newly produced monoclonal antibody to TI-VAMP that improves signal/noise
      immunodetection, we report that TI-VAMP is also present in subsets of axon
      terminals of the adult rat brain. Four distinctive populations of labelled axon
      terminals were identified: 1) the hippocampal mossy fibres of the dentate gyrus
      and of CA3, 2) the striatal peridendritic terminal plexuses in the globus
      pallidus (GP), substantia nigra pars reticulata (SNr), 3) peridendritic plexuses
      in the central nucleus of the amygdala, and 4) the primary sensory afferents in
      the dorsal horn of the spinal cord. The presynaptic localisation of TI-VAMP in
      these locations was demonstrated by co-localisation with synaptophysin.
      Ultrastructural studies showed TI-VAMP labelling over synaptic vesicles in the
      mossy fibres, whereas it was localised in tubulo-vesicular structures and
      multivesicular bodies in the pyramidal cell dendrites. The presynaptic
      localisation of TI-VAMP occurred by P15, so relatively late during development.
      In contrast, dendritic labelling was most prominent during the early post-natal
      period. Co-localisation with markers of neurotransmitters showed that TI-VAMP
      positive terminals are GABAergic in the GP and SNr and glutamatergic in the mossy
      fibre system and in the dorsal root afferents. Most of these terminals are known
      to co-localise with neuropeptides. We found met-enkephalin-immunoreactivity in a
      sizeable fraction of the TI-VAMP positive terminals in the GP, amygdala, and
      dorsal horn, as well as in a few mossy fibre terminals. The function of TI-VAMP
      in subsets of mature axon terminals remains to be elucidated; it could
      participate in the exocytotic molecular machinery and/or be implicated in
      particular growth properties of the mature axon terminals. Thus, the presence of
      TI-VAMP in the mossy fibres may correspond to the high degree of plasticity that
      characterises this pathway throughout adult life.

PMID- 14596850
TI  - Heterogeneity of spike frequency adaptation among medium spiny neurones from the
      rat striatum.
AB  - The main neuronal population of the striatum is composed of the medium spiny
      neurones (MSNs). In fact several sub-populations of MSNs can be distinguished
      according to the striatal compartment (striosomes and matrix) to which they
      belong, their afferents and their sites of projection, their biochemical markers
      and their morphologies. However, these cells are generally described as an
      electrophysiological homogeneous population. Using brain slices from the rat and
      whole cell patch clamp recordings, we show that at P(15) 28% of the MSNs display
      a spike frequency adaptation. While the mean frequency adaptation ratio for non
      adapting cells was 1.07+/-0.01 it reached 2.66+/-0.09 in adapting MSNs and the
      incidence of this frequency adaptation phenotype appeared to be stable during
      post-natal development. Single-cell RT-PCR analysis of mRNAs for mu opioid
      receptors, enkephalin and substance P precursors suggested that adapting MSNs are
      present in both striatal compartments as well as in the direct and indirect
      pathways of the matrix. Adapting neurones were also distinguished from non
      adapting cells by a lower membrane time constant, a higher AP threshold, a
      reduced delay to the first spike and a higher initial firing rate. Micro-domains
      differing by their magnitude of adaptation could be distinguished within the
      spike frequency adaptation process.A subgroup of MSNs exists, showing a marked
      spike frequency adaptation together with other distinct properties, such as
      shorter delay to first spike and membrane time constant, and higher initial
      frequency and action potential threshold. In conclusion, when strong cortical
      inputs are delivered in coincidence, adapting MSNs could not only transmit faster
      the first AP but also exert a sort of cutoff of the transmission due to their
      spike frequency adaptation process.

PMID- 14596851
TI  - Morphology and ultrastructure of rat hippocampal formation after i.c.v.
      administration of N-acetyl-L-aspartyl-L-glutamate.
AB  - N-Acetyl-L-aspartyl-L-glutamate (NAAG) is one of the most abundant neuroactive
      compounds in the mammalian CNS. Our recent observations have suggested that NAAG
      administered into rat cerebral ventricles can cause neuronal death by apparently
      excitotoxic mechanisms that can be antagonized by the N-methyl-D-aspartate
      receptor blockers and by ligands of metabotropic glutamate receptor of Group II.
      Therefore, the principal aim of the present study has been to use quantitative
      morphology, electron microscopy and terminal deoxynucleotidyl transferase
      mediated biotin dUTP nick-end labeling to study a dose- and time-dependence as
      well as regional distribution of neurodegeneration in hippocampi of rats after
      the intraventricular infusion of 0.25 micromol NAAG/ventricle and of equimolar
      doses of L-glutamate (L-GLU) and N-acetyl-L-aspartate (NAA), breakdown products
      of NAAG. The degenerative changes were observed after the infusion of 0.25 and
      1.25 micromol of NAAG/ventricle, but not when a dose of 0.05 micromol of
      NAAG/ventricle was injected into each lateral cerebral ventricle. With a dose of
      0.25 micromol of NAAG/ventricle the number of degenerated neurons reached a
      maximum on the fourth day after the infusion. The neuronal damage following
      bilateral administration of 0.25 micromol of NAAG/lateral cerebral ventricle
      exhibited features of a delayed neuronal degeneration, expressed mainly in the
      layer of dentate granule neurons. The degeneration was characterized on the basis
      of ultrastructural appearance and DNA-fragmentation. The morphological changes
      caused by L-glutamate and NAA were much smaller than those observed after the
      administration of NAAG and displayed a different pattern of regional
      distribution. The present findings suggest that NAAG can cause a loss of
      hippocampal neurons in vivo, apparently resulting from the neurotoxicity of NAAG
      itself.

PMID- 14596852
TI  - Hippocampal apolipoprotein D level depends on Braak stage and APOE genotype.
AB  - Apolipoprotein (APO, gene; apo, protein) D, a member of the lipocalin family, has
      been implicated in several, pathological conditions but neither its physiologic
      function(s) nor ligand(s) has been clearly identified so far. Presuming a role in
      nerve de- and regeneration, several groups investigated apoD alterations in
      Alzheimer's disease (AD). Reported data, however, were not unanimous. We
      determined apoD protein levels in the hippocampus in a large, carefully matched
      autopsy case sample. ApoD levels were compared with the severity of
      neuropathological changes as determined by the Braak classification and with APOE
      genotype, a major risk factor for developing AD. ApoD was found to be related to
      the severity of AD-related neurofibrillary (NF) changes and not to old age alone.
      No correlation was found to amyloid deposits. Brain samples with widespread NF
      changes showed significantly higher apoD than cases with low Braak stages. This
      increase, however, was restricted to the APOE epsilon3/3 group, whereas the APOE
      epsilon4 group did not show significant variations in hippocampal apoD.

PMID- 14596853
TI  - Purinergic P2 receptors trigger adenosine release leading to adenosine A2A
      receptor activation and facilitation of long-term potentiation in rat hippocampal
      slices.
AB  - Electrophysiological recordings were used to investigate the effects of ATP
      analogues on theta-burst-induced long-term potentiation (LTP) in rat hippocampal
      slices. alpha,beta-Methylene ATP (alpha,beta-MeATP; 20 microM) decreased LTP from
      36+/-9% to 17+/-5%, an effect prevented by adenosine A(1) receptor blockade in
      accordance with the localised catabolism of ATP analogues into adenosine, leading
      to adenosine A(1) receptor activation. Thus, to probe the role of extracellular
      ATP, all experiments were performed with the A(1) receptor selective antagonist,
      1,3-dipropyl-8-cyclopentylxanthine (50 nM). In these conditions, alpha,beta-MeATP
      or 5'-adenylylimido-diphosphate (beta,gamma-ImATP; 20 microM) facilitated LTP by
      120%, an effect prevented by the P2 receptor antagonists, pyridoxalphosphate-6
      azophenyl-2'-4'-disulphonic acid (PPADS; 20 microM) or suramin (75 microM), as
      well as by the P2X(1/3)-selective antagonist 8-(benzamido)naphthalene-1,3,5
      trisulfonate (10 microM). The facilitations of LTP by either alpha,beta-MeATP or
      beta,gamma-ImATP (20 microM) were also prevented by both 4-(2-[7-amino-2-(2
      furyl(1,2,4)-triazolo(2,3a)-(1,3,5)triazin-5-yl-amino]ethyl)phenol (50 nM) or 7
      2(-phenylethyl)-5-amino-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c]
      pyrimidine (50 nM), antagonists of facilitatory adenosine A(2A) receptors, were
      occluded by the A(2A) receptor agonist, CGS 21680 (10 nM) and were prevented by
      the protein kinase C inhibitor, chelerythrine (6 microM) and unaffected by the
      protein kinase A inhibitor, H89 (1 microM). Furthermore, beta,gamma-ImATP (20
      microM) enhanced [(3)H]adenosine outflow from rat hippocampal slices by nearly
      150%, an effect prevented by PPADS (20 microM) or suramin (75 microM). The
      adenosine transport inhibitors, nitrobenzylthioinosine (5 microM) and
      dipyridamole (10 microM) also prevented beta,gamma-ImATP (20 microM)-induced
      [(3)H]adenosine outflow and facilitation of LTP. These results suggest that ATP
      analogues facilitate LTP through P2 receptor activation that mainly triggers
      adenosine release leading to the activation of adenosine A(2A) receptors.

PMID- 14596854
TI  - HuC/D confocal imaging points to olfactory migratory cells as the first cell
      population that expresses a post-mitotic neuronal phenotype in the chick embryo.
AB  - In the present study, the expression of the HuC/D RNA-binding proteins, a marker
      of neurons that have left the mitotic cycle, in cells migrating from the
      olfactory neuroepithelium toward the telencephalon in the chick embryo was
      investigated by means of immunofluorescence and confocal laser microscopy.
      Results showed that this migratory cell population is early and massively labeled
      by the a-HuC/D antibody starting from the first olfactory pit stage. At this
      developmental stage, olfactory migratory cells appeared to be the only neuronal
      population that expressed the HuC/D antigens in the whole embryo. In following
      developmental stages, the great majority of migratory cells, the number of which
      increased progressively, continued to be heavily immunopositive for the a-HuC/D
      antibody while immunopositivity to this antibody begins to be detected in other
      regions of the nervous system. HuC/D immunopositivity persisted until stage 30 HH
      (about 6.5 days), the later developmental stage investigated in this study, when
      colocalization with GnRH was detected. Negativity to the anti-proliferating cell
      nuclear antigen (anti-PCNA) immunostaining, a marker of S-phase, showed that
      migratory olfactory cells have left the mitotic cycle. Altogether, these results
      suggest that we have identified the first population of post-mitotic neurons in
      the developing nervous system of the chick embryo.

PMID- 14596855
TI  - Role of beta-catenin in the developing cortical and hippocampal neuroepithelium.
AB  - beta-Catenin plays a pivotal role in Wnt signaling during embryogenesis and is a
      component of adherens junctions. Since targeted disruption of the beta-catenin
      gene is lethal at gastrulation we have used a D6-Cre mouse line for conditional
      inactivation of beta-catenin in the mouse cerebral cortex and hippocampus after
      embryonic day (E) 10.5. In D6-Cre floxed beta-catenin mice, hippocampal CA1-CA2
      fields are disrupted in similar manner as in Wnt-3a and LEF-1 mutants. The cortex
      of D6-Cre floxed beta-catenin mutants is strongly affected which contrasts with
      the normal cortex observed in Wnt-3a and LEF-1 mutants. Severe abnormalities in
      the organization of the neuroepithelium are observed that include disrupted
      interkinetic nuclear migration, loss of adherens junctions, impaired radial
      migration of neurons toward superficial layers and decreased cell proliferation
      after E15.5. At newborn stage, a premature disassembly of the radial glial
      scaffold and increased numbers of astrocytes are found in the cortex.

PMID- 14596856
TI  - Aberrant protein expression in cerebral cortex of fetus with Down syndrome.
AB  - Down syndrome is the most common birth defect associated with mental retardation.
      Identifying proteins that are aberrantly expressed therefore helps to understand
      how chromosomal imbalance leads to subnormal intelligence in Down syndrome. In
      the present study, we generated a fetal brain map with the use of an analytical
      method based on two-dimensional electrophoresis coupled with mass spectrometry
      and searched the proteome for differential protein expression. Among 49 proteins
      analyzed in seven control and nine Down syndrome fetuses, we found 11 proteins
      that have been deregulated in cerebral cortex of fetal Down syndrome. While
      double-strand break repair protein rad 21 homologue, eukaryotic translation
      initiation factor 3 subunit 5, mixed lineage leukemia septin-like fusion protein
      B and heat shock protein 75 were increased; beta-amyloid precursor-like protein
      1, tropomyosin 4-anaplastic lymphoma kinase fusion oncoprotein type 2, Nck
      adaptor protein 2, Src homology domain growth factor receptor bound 2-like
      endophilin B2, beta tubulin, septin 7 and hematopoietic stem/progenitor cells 140
      were decreased. The current data suggest that misexpression of proteins that have
      functions ranging from signaling to cellular structural organization could
      contribute to or reflect brain dysgenesis in Down syndrome.

PMID- 14596857
TI  - Mapping oxytocin receptor gene expression in the mouse brain and mammary gland
      using an oxytocin receptor-LacZ reporter mouse.
AB  - The hypothalamic nonapeptide oxytocin (OT) has an established role as a
      circulating hormone but can also act as a neurotransmitter and as a
      neuromodulator by interacting with its central OT receptor (OTR). To understand
      the role of the OTR in the mouse brain we investigated the expression of the OTR
      gene at the cellular level. We targeted the lacZ reporter gene to the OTR gene
      locus downstream of the endogenous OTR regulatory elements. Using lactating mouse
      mammary gland as a control for OTR promoter directed specificity of lacZ gene
      expression, X-gal histochemistry on tissue sections confirmed that gene
      expression was restricted to the myoepithelial cells. We also identified for the
      first time in mice the expression of the OTR gene in neighbouring adipocytes.
      Further, investigation in the mouse brain identified numerous nuclei containing
      neurons expressing the OTR gene. Whilst some of these regions had been described
      for rat or sheep, the OTR-LacZ reporter mouse enabled the identification of novel
      sites of central OTR gene expression. These regions include the accessory
      olfactory bulb, the medial septal nucleus, the posterolateral cortical amygdala
      nucleus, the posterior aspect of the basomedial amygdala nucleus, the medial part
      of the supramammillary nucleus, the dorsotuberomammillary nucleus, the medial and
      lateral entorhinal cortices, as well as specific dorsal tegmental, vestibular,
      spinal trigeminal, and solitary tract subnuclei. By mapping the distribution of
      OTR gene expression, depicted through histochemical detection of beta
      galactosidase, we were able to identify single OTR gene expressing neurons and
      small neuron clusters that would have remained undetected by conventional
      approaches. These novel sites of OTR gene expression suggest additional functions
      of the oxytocinergic system in the mouse. These results lay the foundation for
      future investigation into the neural role of the OTR and provide a useful model
      for further study of oxytocin functions in the mouse.

PMID- 14596858
TI  - Dendrite-associated opioid-binding cell adhesion molecule localizes at
      neurosecretory granules in the hypothalamic magnocellular neurons.
AB  - Opioid-binding cell adhesion molecule (OBCAM) is a member of the immunoglobulin
      superfamily containing limbic system-associated membrane protein (IgLON) subgroup
      of glycosylphosphatidylinositol-anchored immunoglobulin cell adhesion molecules.
      We have previously found that OBCAM is localized preferentially to dendrites
      compared with somata and terminals of hypothalamic vasopressin-secreting
      magnocellular neurons. This localization indicates that OBCAM is one of the
      dendrite-associated cell adhesion molecules. In the present study, we further
      characterized the localization and the sorting mechanism, and activity-dependent
      changes of this molecule in vasopressin-secreting magnocellular dendrites.
      Confocal microscopic observation revealed the preferential localization of OBCAM
      at the neurosecretory granules in the vasopressin-positive dendrites. Electron
      microscopic observation using chromogen-intensified and gold-conjugated methods
      also demonstrated the OBCAM labeling at most of the neurosecretory granules
      within the dendrites, while the labeling within the somata was observed at only a
      few neurosecretory granules. I.c.v. colchicine administration resulted in the
      disappearance of OBCAM immunoreactivity from the dendrites and in its concomitant
      accumulation at the somata, suggesting that OBCAM is synthesized at the somata
      and transported to the dendrites by dendrite-associated neurosecretory granules.
      During the postnatal development, OBCAM immunoreactivity targeted to vasopressin
      positive dendrites became clear from at least 3 weeks after birth, although it
      appeared at only a few somata 2 weeks after birth. Phosphatidylinositol specific
      phospholipase C treatment of the membrane fraction of the supraoptic homogenate
      solubilized OBCAM. Kilon, another IgLON member, was also shown to localize at the
      neurosecretory granules of vasopressin-positive dendrites via the
      glycosylphosphatidylinositol anchor. High K(+)-stimulation appeared to cause the
      diffusion of OBCAM-labeled gold particles from neurosecretory granules together
      with the exocytosis. These findings indicate that OBCAM is synthesized within the
      somata, attached to vasopressin neurosecretory granules via the
      glycosylphosphatidylinositol anchor, and transported to the dendrites. Moreover,
      the subcellular localization of OBCAM is changed in an activity-dependent manner.

PMID- 14596859
TI  - Post-training administration of a synthetic peptide ligand of the neural cell
      adhesion molecule, C3d, attenuates long-term expression of contextual fear
      conditioning.
AB  - The neural cell adhesion molecule (NCAM) plays a key role in synaptic plasticity
      and memory formation. We have recently developed a synthetic peptide, termed C3d,
      which, through the binding to the first, N-terminal immunoglobulin-like (Ig)
      module in the extracellular portion of NCAM, has been shown to promote neurite
      outgrowth and synapse formation in vitro, and to interfere with passive avoidance
      memory in rats in vivo. In this study, we investigated whether the i.c.v.
      administration of C3d, either 5.5 h after or 2 days before training, could be
      effective to modulate the strength at which emotional memory for aversive
      situations is established into a long-term memory. The effects of the peptide
      were evaluated in adult male Wistar rats trained in the contextual fear
      conditioning task. The results indicated that C3d significantly reduced the
      subsequent long-term retention of the conditioned fear response when administered
      5.5 h post-training, as indicated by retention tests performed 2-3 and 7 days
      post-training. However, this treatment failed to influence conditioning for this
      task when injected 2 days pre-training. Additional experiments showed that C3d
      did not influence the emotional or locomotor behaviour of the animals, when
      tested in the open field task. Furthermore, hippocampal levels of microtubule
      associated protein 2 (MAP2), Synaptophysin and NCAM were found unchanged when
      evaluated by enzyme-linked immunosorbent assay in crude synaptosomal preparations
      2 days after peptide i.c.v. injection. Therefore, post-training injection of this
      synthetic peptide was efficient to attenuate the strength at which memory for
      contextual fear conditioning was enduringly stored, whilst it did not affect the
      acquisition of new memories. In addition to further support the view that NCAM is
      critically involved in memory consolidation, the current findings suggest that
      the NCAM IgI module is a potential target for the development of therapeutic
      drugs capable to reduce the cognitive impact induced by exposure to intensive
      stress experiences.

PMID- 14596861
TI  - Localization of the m5 muscarinic cholinergic receptor in rat circle of Willis
      and pial arteries.
AB  - The expression and microanatomical localization of the muscarinic cholinergic m5
      receptor subtype was investigated in rat circle of Willis and pial arteries by in
      situ hybridization, immunoblotting and immunohistochemistry. In situ
      hybridization histochemistry revealed a strong signal in the endothelium of
      circle of Willis and pial arteries and a moderate signal in the tunica media of
      the same arteries, within smooth muscle. Exposure of membranes of arteries to
      anti-m5 receptor protein antibodies caused the development of a band of
      approximately 81 kDa. Immunohistochemistry revealed the accumulation of m5
      receptor protein immunoreactivity primarily within endothelium of circle of
      Willis and cerebral arteries and to a lesser extent in the tunica media, within
      smooth muscle. Medium (external diameter 200-100 microm) and small-sized
      (external diameter smaller than 100 microm) pial arteries displayed a
      significantly higher immune staining than large-sized pial arteries or circle of
      Willis arteries. The above data that are consistent with recent functional
      studies reporting cholinergic dilation of cerebral blood vessels mediated via a
      m5 receptor, have shown that both endothelial and muscular components of cerebral
      arteries synthesize and express a muscarinic m5 receptor. In view of the peculiar
      localization in cerebral vessels, handling of the muscarinic m5 receptor may be
      considered as an approach in the treatment of cerebrovascular disease.

PMID- 14596860
TI  - Neurochemical and anatomical identification of fast- and slow-firing neurones in
      the rat dorsal raphe nucleus using juxtacellular labelling methods in vivo.
AB  - GABA neurones in the dorsal raphe nucleus (DRN) influence ascending 5
      hydroxytryptamine (5-HT) neurones but are not physiologically or anatomically
      characterised. Here, in vivo juxtacellular labelling methods in urethane
      anaesthetised rats were used to establish the neurochemical and morphological
      identity of a fast-firing population of DRN neurones, which recent data suggest
      may be GABAergic. Slow-firing, putative 5-HT DRN neurones were also identified
      for the first time using this approach. Fast-firing, DRN neurones were
      successfully labelled with neurobiotin (n=10) and the majority (n=8/10) were
      immunoreactive for the GABA synthetic enzyme glutamic acid decarboxylase. These
      neurones were located in the DRN (mainly lateral regions), and consistently fired
      spikes with short width (1.1+/-0.1 ms) and high frequency (12.1+/-2.0 Hz). In
      most cases spike trains were regular but displayed low frequency oscillations (1
      2 Hz). These neurones were morphologically heterogeneous but commonly had
      branching axons with varicosities and dendrites that extended across DRN
      subregions and the midline. Slow-firing DRN neurones were also successfully
      labelled with neurobiotin (n=24). These neurones comprised a population of
      neurones immunopositive for 5-HT and/or tryptophan hydroxylase (n=12) that fired
      broad spikes (2.2+/-0.2 ms) with high regularity and low frequency (1.7+/-0.2
      Hz). However, a slow-firing, less regular population of neurones immunonegative
      for 5-HT/tryptophan hydroxylase (n=12) was also apparent. In summary, this study
      chemically identifies fast- and slow-firing neurones in the DRN and establishes
      for the first time that fast-firing DRN neurones are GABAergic. The
      electrophysiological and morphological properties of these neurones suggest a
      novel function involving co-ordination between GABA and 5-HT neurones dispersed
      across DRN subregions.

PMID- 14596862
TI  - Ultrastructural and behavioural changes precede amyloid deposition in a
      transgenic model of Alzheimer's disease.
AB  - We describe the thorough characterisation of a new transgenic mouse line
      overexpressing the 695-amino acid isoform of human amyloid precursor protein
      harbouring the Swedish double familial Alzheimer's disease mutation. This line,
      referred to as TAS10, exhibits neuropathological features and cognitive deficits
      that are closely correlated to the accumulation of Abeta in their brain and that
      are reminiscent of those observed in AD. Data on the TAS10 line are presented at
      five time points: 2, 6, 12, 18 and 24 months in a longitudinal study. The TAS10
      line is characterised by the following changes: i) significant age-related
      increases in the levels of total and individual species (1-40, 1-42) of beta
      amyloid in the brains of transgenics compared with non-transgenic littermates;
      ii) transgenic mice showed pronounced spatial learning deficits in the Morris
      water maze at 6 months and working memory deficits by 12 months; iii) amyloid
      plaque and associated pathologies were observed by the 12-month time point and
      the burden increased substantially, particularly in the cortex, by 18 months; iv)
      electron microscopy of the hippocampus of transgenic mice showed evidence of
      abnormal ultrastructural features such as dystrophic neurites and lipid deposits
      that developed from 6 months and increased in number and severity with age.
      Morphometric studies demonstrate that the synapse to neuron ratio is higher in
      transgenics than in control mice at 12 months, but this ratio decreases as they
      age and synapse size increases. Thus, this mouse model exhibits a close
      correlation of amyloid burden with behavioural deficits and ultrastructural
      abnormalities and so represents an ideal system to study the mechanisms
      underlying the impact of amyloid pathology on CNS function.

PMID- 14596863
TI  - Potential role of glial cell line-derived neurotrophic factor receptors in Muller
      glial cells during light-induced retinal degeneration.
AB  - Glial cell line-derived neurotrophic factor (GDNF), neurturin (NTN) and their
      receptors (GFRalpha1, GFRalpha2 and Ret) play an important role in the survival
      of neurons in the central and peripheral nervous system. For example, GDNF as
      well as other trophic factors promotes photoreceptor survival during retinal
      degeneration. Recent studies have proposed that part of neurotophic rescue of
      photoreceptors may be indirect, mediated by interaction of the neurotrophic
      factors with other cell types, that in turn release secondary factors that act
      directly on photoreceptors. In the present study, we examined the GDNF receptor
      expression in control and light-damaged retina, and found that GFRalpha2 protein
      is upregulated in retina-specific Muller glial cells during photoreceptor
      degeneration. We also examined the effect of GDNF or NTN on cultured Muller
      cells. Exogenous GDNF increased brain-derived neurotrophic factor, basic
      fibroblast growth factor and GDNF, but not NTN mRNA production. On the other
      hand, NTN increased NTN, but not GDNF mRNA production in cultured Muller cells.
      These observations suggest that GDNF, NTN and their receptors are involved in the
      regulation of trophic factor production in retinal glial cells, and that
      functional glia-neuron network may utilize GDNF family for the protection of
      neural cells during retinal degeneration.

PMID- 14596865
TI  - Characterization of the neurochemical content of neuronal populations of the
      lamina terminalis activated by acute hydromineral challenge.
AB  - The lamina terminalis (LT) contains three main regions, namely the subfornical
      organ (SFO), the median preoptic nucleus (MnPO) and the vascular organ of the LT
      (OVLT). Although LT is recognized of paramount importance in the regulation of
      hydromineral homeostasis, identity of the neurocircuits interconnecting the SFO
      and OVLT to the MnPO is not known. Furthermore, the phenotype of neuronal
      populations activated during acute hydromineral challenge is not yet determined.
      By using the high cellular resolution of the in situ hybridization histochemistry
      (ISHH), we investigated whether a furosemide-induced fluid and electrolyte
      depletion might modify both putative GABAergic and glutamatergic systems within
      the LT. We show that acute furosemide treatment (4 h) significantly reduced the
      expression of GAD67 mRNA, the active holoenzyme predictive of GABA synthesis,
      within the SFO. A strong tendency toward a reduction of GAD67 signal was also
      observed in the OVLT and MnPO. The hydromineral challenge did not alter the
      expression of GAD65 and type 2 vesicular glutamate transporter (vGlut2) mRNA in
      all the structures of the LT. Furosemide treatment was associated with a
      reduction in the population of GAD67-containing neurons in the periphery of the
      SFO and dorsal part of the MnPO. Contrastingly, GAD65-containing cells were shown
      to be increased in the OVLT and no change was observed for the vGlut2-containing
      neurons in the whole LT. By combining ISHH with immunohistochemistry (Fos
      immunoreactivity), we report that furosemide-induced water and sodium depletion
      did essentially recruit a glutamatergic network throughout the LT, although
      GABAergic neurons were specifically activated in the ring of the SFO and in the
      OVLT. The MnPO, the region of the LT that is considered as being an integrative
      area for sensory inputs arising from the SFO and OVLT, showed exclusive
      activation of excitatory neuronal populations. Taken together these results
      suggest that acute water and Na(+) depletion diminish the efficacy of the
      GABAergic system and mainly activates excitatory neuronal pathways in the regions
      of the LT.

PMID- 14596864
TI  - Increased phosphorylation of the GluR1 subunit of spinal cord alpha-amino-3
      hydroxy-5-methyl-4-isoxazole propionate receptor in rats following intradermal
      injection of capsaicin.
AB  - Ionotropic glutamate receptors are ligand-gated ion channels that help mediate
      rapid excitatory neurotransmission in the CNS. alpha-Amino-3-hydroxy-5-methyl-4
      isoxazole propionate (AMPA) receptors are critical for synaptic plasticity in
      central nociceptive transmission. The current study was designed to investigate
      the role of the AMPA receptor subunit, GluR1, and its phosphorylated forms (at
      Ser-831 and Ser-845) in central sensitization in rat spinal cord. Western blots
      and immunohistochemistry were performed to examine the expression and
      localization of GluR1 and the phosphorylated forms of GluR1 (phospho-GluR1) at
      Ser-831 and Ser-845 with specific antibodies. Results showed that immunolabeling
      of GluR1 protein in rat spinal cord can be detected at 110 kD, and two phospho
      GluR1 proteins were found at 106 kD. A significant upregulation of phospho-GluR1
      both at Ser-831 and Ser-845 was found by 5 min after capsaicin treatment, and
      this increase lasted at least 60 min. Immunostaining showed that GluR1 and its
      phosphorylated forms were localized in the superficial laminae of dorsal horn and
      quantitative image analysis supported the immunoblotting results. Our findings
      are consistent with the suggestions that AMPA receptors show increased
      responsiveness because of their phosphorylation and that this may contribute to
      central sensitization following intradermal injection of capsaicin.

PMID- 14596866
TI  - Anatomical and physiological study of respiratory motor innervation in lampreys.
AB  - The innervation of gill muscles of lampreys was investigated in a semi-intact
      preparation in which the respiratory rhythm was maintained for more than 2 days.
      Lesion experiments showed that the muscles of gill 1 are innervated by nerves VII
      (facial) and IX (glossopharyngeal), and those of gill 2 by nerve IX and the first
      branchial branch of nerve X (vagal). The other gills are supplied by the other
      branchial branches of nerve X. Retrograde tracers, injected in peripheral
      respiratory nerves, showed that branchial muscles are innervated by VII, IX and X
      motoneurons. Within the X nucleus, the motoneuron pools were branchiotopically
      organized, but with considerable rostro-caudal overlap. Electrophysiological
      recordings were used to show that the onset of activation of the branchial
      muscles was increasingly delayed with the distance from the brainstem, but that
      motoneuronal activity recorded with surface electrodes began at approximately the
      same time in all pools. The conduction velocity of VII and caudal X motor axons
      was found to be the same. Differences in the length of motoneuron axons appear to
      account for the rostro-caudal delay in gill contraction. The data presented here
      provide a much needed anatomical and physiological basis for further studies on
      the neural network controlling respiration in lampreys.

PMID- 14596867
TI  - GABA transmission in the ventral pallidum is not involved in the control of
      latent inhibition in the rat.
AB  - Latent inhibition describes a process of learning to ignore stimuli of no
      consequence, and is disrupted in acute, positive-symptomatic schizophrenia.
      Understanding the neural basis of latent inhibition in animals may help to
      elucidate the neural dysfunction underlying positive schizophrenic symptoms in
      man. Evidence suggests a crucial role for dopamine transmission in the nucleus
      accumbens in the control of latent inhibition. The present studies investigated
      the role of the GABA-ergic efferent from the nucleus accumbens to the ventral
      pallidum in latent inhibition. The GABA(A) agonist muscimol (4.56 ng/microl), and
      antagonist picrotoxin (0.2 microg/microl), were infused into the ventral
      pallidum, and effects on latent inhibition were assessed using a conditioned
      suppression procedure. Neither drug produced specific effects on latent
      inhibition when given alone and, in the case of muscimol, failed to reverse the
      disruption of latent inhibition induced by systemic amphetamine. In addition to
      significant non-specific drug effects, a positive control experiment revealed
      that intra-pallidal picrotoxin significantly enhanced locomotion, suggesting that
      our manipulations of ventral pallidal GABA function were behaviourally effective.
      We conclude that modulating ventral pallidal GABA transmission does not affect
      latent inhibition. The implications of this finding for theories of the neural
      circuitry mediating latent inhibition and for understanding the functional role
      of ventral pallidal GABA transmission are discussed.

PMID- 14596869
TI  - Hepatocyte growth factor/scatter factor in development, inflammation and
      carcinogenesis: its expression and role in oral tissues.
AB  - Hepatocyte growth factor (HGF) was discovered as a potent mitogen for adult
      hepatocytes from the plasma of patients with fulminant hepatic failure. It is now
      known to be a broad-spectrum, multi-functional mitogen, motogen and morphogen.
      The activities of HGF are mediated through the signalling pathway of its
      receptor, c-Met. During tooth development, HGF is expressed in the dental papilla
      and c-Met is expressed in the inner enamel epithelium. The expression of HGF and
      c-Met indicates that HGF is involved in morphogenesis of the tooth by mediating
      epithelial-mesenchymal interactions. In the mature tooth, HGF expression by
      fibroblasts is enhanced in pulpitis and mediated through the induction of
      prostaglandin (PG) E(2); it is induced not only by inflammatory cytokines, but
      also by components of oral bacteria. Consequently, concentrations of HGF in
      gingival crevicular fluid (GCF) increase in periodontitis. The mitogenic and
      other biological activities, such as angiogenesis, of HGF contribute towards
      wound healing. Both HGF and c-Met are expressed in the developing tongue, and the
      signalling pathway of the latter is shown to be essential for myogenesis.
      Dysregulation of c-Met signalling is observed in carcinogenesis, but HGF also has
      cytotoxic activity to certain tumour cells. The reason for the discrepancy
      between these observations is not clear at present.

PMID- 14596868
TI  - Reduced activity of hippocampal group-I metabotropic glutamate receptors in
      learning-prone rats.
AB  - Following the hypothesis of the "signal-to-noise" ratio we examined whether
      changes in the activity of group-I metabotropic glutamate (mGlu) receptors in the
      hippocampus are associated with a condition that specifically enhances the
      learning capacity in rats. As a model, we used rats that had been nursed by
      mothers drinking a solution of corticosterone (13.5 mg of daily intake of
      corticosterone hemisuccinate) during the lactation period. These rats were prone
      to learn, as indicated by a better performance in a passive avoidance test.
      Stimulation of polyphosphoinositide (PI) hydrolysis by the mGlu receptor agonist,
      1S,3R-1-amino-cyclopentan-1,3-dicarboxylic acid (1S,3R-ACPD), was attenuated in
      hippocampal slices prepared from corticosterone-nursed male and female rats at 30
      or 60 days of postnatal life, an age at which an increased learning capacity
      could be demonstrated. This effect was specific because the PI response to
      carbamylcholine was unchanged. A reduced PI hydrolysis in corticosterone-nursed
      rats was also observed when group-I mGlu receptors (i.e. mGlu1 and -5 receptors)
      were selectively activated using 3,5-dihydroxyphenylglycine or 1S,3R-APCD
      combined with the selective group-II mGlu receptor antagonist, 2S-2-amino-2
      (1S,2S-2-carboxycyclopropan-1-yl)-3-(xanth-9-yl)propionate. Western blot analysis
      showed a selective reduction in the expression of mGlu1a receptor protein in the
      hippocampus of corticosterone-nursed rats, whereas expression of mGlu5 and
      mGlu2/3 receptors was unchanged. The reduction in mGlu-receptor mediated PI
      hydrolysis in the hippocampus may contribute to the greater learning capacity of
      corticosterone-nursed rats by reducing the background noise over which a specific
      signal must be superimposed during learning. This hypothesis was supported by the
      evidence that mGlu-receptor stimulated PI hydrolysis was amplified in hippocampal
      slices from rats subjected to a passive avoidance learning paradigm, and that
      this amplification was greater in slices from corticosterone-nursed rats of both
      sexes.

PMID- 14596870
TI  - Influence of antifungal polyenes on the adhesion of Candida albicans and Candida
      glabrata to human epithelial cells in vitro.
AB  - Candidal adherence to mucosal surfaces is considered as the first step in the
      pathogenesis of oral candidiasis. We examined the effect of antifungal polyenes,
      amphotericin B, nystatin and natamycin, at sublethal and minimum inhibitory
      concentrations (MICs) on the adherence of Candida albicans and Candida glabrata
      to HeLa cervical carcinoma and HSC-3 oral squamous cell carcinoma cells. A total
      of six oral Candida isolates were used throughout the study. Two Candida strains,
      C. albicans (44990) and C. glabrata (MYA-275) were obtained from ATCC. Four
      Candida strains, C. albicans 19 and 24 and C. glabrata 15 and 21, were isolated
      from patients with documented Candida-associated denture stomatitis. Cells were
      either incubated with Candida in the presence of the drug, or pre-incubated with
      yeasts and exposed subsequently to the drug. In the drug-free controls, the mean
      number of C. albicans yeasts associated with HeLa cells obtained from all
      experiments (130.1+/-10.1 yeasts/mm(2)) was significantly greater than that for
      HSC-3 cells (114.7+/-10.1 yeasts/mm(2); P<0.025). For C. glabrata, the mean
      adherence to HeLa and HSC-3 cells was 84.4+/-5.5 and 84.4+/-3.3 yeasts/mm(2),
      respectively, and these values were not statistically different (P>0.4). Candidal
      adherence was significantly reduced when the tested polyenes were present during
      the "adherence phase". The obtained values were significantly different from the
      controls, except for the effect of nystatin at the MIC on the adherence of C.
      glabrata strain MYA-275 to HeLa cells (P<0.375). Amphotericin B had the highest
      effect against both Candida species, reducing adherence by approximately 50 and
      approximately 60%, at the MIC and sublethal concentrations, respectively. The
      susceptibility of cell-associated Candida to polyenes was decreased markedly and
      the treatment did not result in significant detachment of adherent yeasts. The
      reduction in adherence was between 2 and 10%, when compared to the drug-free
      controls. These findings suggest that sub-therapeutic levels of polyenes that are
      likely to persist in the oral cavity following topical treatment may modulate
      candidal colonization when present during the "adherence phase".

PMID- 14596871
TI  - A 100 kDa vanadate and lanzoprazole-sensitive ATPase from Streptococcus mutans
      membrane.
AB  - The cariogenic potential of Streptococcus mutans is due to the production of
      organic acids derived from energy metabolism, which implies the need of
      mechanisms for the organism to tolerate this acidic environment. The F(1)F(o)
      ATPase is generally considered as the main enzyme responsible for cytoplasmic
      proton extrusion, but mutations that resulted in a 50% reduction in F(1)F(o)
      ATPase activity in S. mutans still allowed the micro-organism to grow and extrude
      acid, keeping the intracellular pH one pH unit above the extracellular ambient.
      This finding suggests the existence of other enzymatic (or cellular) mechanisms
      that keep the cytosolic pH neutral during micro-organism growth. This paper
      describes a membrane protein in S. mutans, with a molecular weight of 100 kDa,
      which exhibits ATPase activity inhibited by classic inhibitors of P-type ATPases
      (orthovanadate) and H(+),K(+)-ATPase (lanzoprazole), has an optimum pH comparable
      to other H(+)-ATPases and undergoes phosphorylation during the catalytic
      reaction, like that of H(+)-ATPases described in yeast and plant plasma membrane.
      Together, these results strongly suggest that the enzyme we describe here is a P
      type H(+)-ATPase or H(+),ion-ATPase that can act in association with F(1)F(o)
      ATPase during the growth of the S. mutans.

PMID- 14596872
TI  - Tumour necrosis factor-alpha and apoptosis in the rat temporomandibular joint.
AB  - The purpose of this investigation was to investigate the roles that tumour
      necrosis factor-alpha (TNF-alpha) and apoptosis play during acute inflammation of
      the temporomandibular joint (TMJ). Adult male Sprague-Dawley rats were injected
      with complete Freund's adjuvant (CFA) into the TMJ or kept as uninjected
      controls. The TMJ tissues were removed 2 days post-injection to mimic conditions
      of acute inflammation and analysed for changes in expression of TNF-alpha, the
      receptor TNF-R1, caspase-3 and -8, and apoptosis. Concentrations of TNF-alpha,
      TNF-R1, caspase-3 and -8, and apoptosis were significantly elevated in CFA
      injected animals compared to uninjected controls. Tissue incubation with TNF
      alpha caused a significant increase in caspase-3 and -8. Also, levels of
      apoptosis were significantly increased during inflammation, which could be
      inhibited by the addition of either anti-TNF-alpha neutralising antibody or
      caspase inhibitors. TNF-alpha may play a significant role in the onset of acute
      CFA-induced TMJ inflammation, and activation of apoptosis signalling pathways may
      be involved.

PMID- 14596873
TI  - Sensory experiences in relation to pulpal nerve activation of human teeth in
      different age groups.
AB  - There are no data on the correlation of intradental nerve activity and sensation
      from intact human teeth. We used microneurography to examine this relation and to
      determine whether it changes with age. Fifteen informed and healthy male
      volunteers were divided into three age groups: group A (18.6+/-1.82 years, mean+/
      standard deviation (S.D.)), group B (38.4+/-2.70 years) and group C (64.0+/-4.06
      years). Ratings of perceived pain intensity to thermal stimulation were obtained
      using a visual analogue scale (VAS). In addition, each subject chose one or two
      words from the short-form McGill Pain Questionnaire to describe perceived pain. A
      total of 90 single pulpal axons were studied with microneurography at the same
      time as the sensory experiences were recorded. Mean conduction velocities and
      variance estimates correlated closely with age. With advancing age, first, the
      percentage of teeth from which the subjects did not perceive any sensations to
      thermal stimulation increased, second, units responding to heat stimulus
      decreased, and third, latencies of sensation induced by thermal stimulation
      increased. In addition, a burst of afterdischarges following thermal stimulation
      and neural discharges evoked by thermal stimulation produced no sensation only in
      some of group B and C units. In contrast, no significant difference was found
      among three groups in VAS scores and words to describe the perceived pain to
      thermal stimulation. These results suggest that pulpal afferents were activated
      by the same mechanism(s); the hydrodynamic mechanism works immediately after
      thermal stimulation and is possibly followed by direct activation of some nerves,
      especially slow conducting fibres. In older tooth pulps, the decrease in the
      number of fast conducting afferents and mineral apposition of dentinal tubules
      impaired the nerve activation, especially by heat, as per the hydrodynamic
      mechanism. Spike discharges without sensation in older individuals were suggested
      to be due to insufficient spatial and temporal summation and may be involved with
      abnormal uncomfortable sensations.

PMID- 14596874
TI  - mRNA expression and phenotype of odontogenic tumours in the v-Ha-ras transgenic
      mouse.
AB  - Ameloblastomas are the most common odontogenic neoplasia in humans, and although
      typically considered locally invasive and benign, frequently recur subsequent to
      surgical resection. The Tg.AC transgenic mouse carrying the v-Ha-ras oncogene has
      been found to spontaneously develop ameloblastoma-like tumours (35% by 1 year of
      age) that are rare in the wild type FVB background strain. OBJECTIVE: The purpose
      of this study was to characterise the mRNA expression of genes in the mouse
      tumours that are either expressed in human ameloblastomas or essential for normal
      odontogenesis and to correlate the expression to the histological phenotype.
      STUDY METHODS: Histological, immunohistochemical and RT-PCR studies were used to
      evaluate clinically demonstrable odontogenic tumours occurring spontaneously in
      seven Tg.AC v-Ha-ras transgenic mice (homozygous, at 7 months of age or
      heterozygous at 11 months of age). RESULTS: Most genes profiled were expressed in
      all tumour samples, however three (amelogenin, matrix metalloproteinase-20 (MMP
      20) and Dlx7) displayed differential expression. In addition, only the most
      highly differentiated tumour stained positively for collagen. In most cases, the
      variable expression could be explained by reference to the histological
      phenotype, although differences in gene expression were apparent within the Type
      2 and the mixed phenotype tumours. CONCLUSIONS: These data confirm that many of
      the genes thought to be important in odontogenesis and odontogenic tumour
      formation in humans are also expressed in these murine ameloblastoma-like tumours
      however genes associated with terminal differentiation of ameloblasts demonstrate
      differential expression between the tumour phenotypes.

PMID- 14596875
TI  - Genetic diversity of Actinomyces naeslundii genospecies 2 in mother-child pairs.
AB  - Actinomyces naeslundii genospecies 2 (gsp-2) are members of the autochthonous
      oral flora. Chromosomal DNA fingerprinting (CDF) with SmaI revealed extensive
      genetic diversity among A. naeslundii gsp-2 strains within individual mothers and
      children. There was a low prevalence of genotype match among A. naeslundii gsp-2
      strains between all mother and child pairs.

PMID- 14596876
TI  - Upstream of Ikaros.
AB  - Haematopoiesis - the process by which pluripotent haematopoietic stem cells
      choose to become lymphocytes, myeloid cells, red blood cells or platelets - has
      long been a useful model to study cellular commitment and differentiation. Each
      cell type is defined by lineage-specific patterns of gene expression. The DNA
      binding protein Ikaros is an important regulator of haematopoiesis and recent
      work promises to shed light on how Ikaros itself is regulated.

PMID- 14596877
TI  - The good, the bad and the ugly--APCs of the eye.
AB  - Dendritic-cell (DC) populations throughout the body have a wide range of features
      in common, which are associated with their primary function in antigen
      presentation. The unique immune milieu of the anterior segment of the eye is
      characterized by a selective DC-dependent inability to develop delayed
      hypersensitivity responses following antigen invasion into the eye. Recent
      research papers provide evidence that different maturation stages of DC subsets
      are detectable at different corneal sites. Thus, the corneal DC, as well as the
      DC and the macrophages in the iris and ciliary body, have the potential of
      determining the outcome of immunity or tolerance within this organ.

PMID- 14596879
TI  - Vitamin C, respiratory infections and the immune system.

PMID- 14596878
TI  - Is innervation an early target in autoimmune diabetes?
AB  - In the non-obese diabetic (NOD) mouse, a spontaneous model of type 1 diabetes
      (T1D), recent evidence suggests that Schwann cells (Scs) and neurons surrounding
      insulin-producing beta cells of the islets of Langerhans are destroyed before
      beta cells. During normal perinatal development, macrophages (MPhi) are involved
      in phagocytosis of apoptotic neurons. Pertinently, MPhi are already present at
      birth in NOD pancreata. Their possible abnormal control of nerve phagocytosis,
      together with transient beta-cell hyperactivity and lymphocyte anomalies, might
      conjointly participate in T1D pathogenesis.

PMID- 14596880
TI  - Unravelling dopamine (and catecholamine) physiopharmacology in lymphocytes: open
      questions.

PMID- 14596882
TI  - Infection of autoreactive B lymphocytes with EBV, causing chronic autoimmune
      diseases.
AB  - I hypothesize that human chronic autoimmune diseases are based on infection of
      autoreactive B lymphocytes by Epstein-Barr virus (EBV), in the following proposed
      scenario. During primary infection, autoreactive B cells are infected by EBV,
      proliferate and become latently infected memory B cells, which are resistant to
      the apoptosis that occurs during normal B-cell homeostasis because they express
      virus-encoded anti-apoptotic molecules. Genetic susceptibility to the effects of
      B-cell infection by EBV leads to an increased number of latently infected
      autoreactive memory B cells, which lodge in organs where their target antigen is
      expressed, and act there as antigen-presenting cells. When CD4(+) T cells that
      recognize antigens within the target organ are activated in lymphoid organs by
      cross-reactivity with infectious agents, they migrate to the target organ but
      fail to undergo activation-induced apoptosis because they receive a co
      stimulatory survival signal from the infected B cells. The autoreactive T cells
      proliferate and produce cytokines, which recruit other inflammatory cells, with
      resultant target organ damage and chronic autoimmune disease.

PMID- 14596883
TI  - Hematopoietic stem cells: generation and manipulation.
AB  - Hematopoietic stem cells (HSCs) are at the forefront of both basic stem cell
      research and clinical applications. Regenerative medicine has recently become a
      viable form of therapy and can potentially cure several diseases. The generation
      of blood cells from embryonic stem cells and the manipulation of HSCs continue to
      provide insights into other stem cell systems. The importance of HSCs as a model
      of an ideal source for cell therapy is increasing.

PMID- 14596884
TI  - The genetics of human systemic lupus erythematosus.
AB  - Genetic dissection of human systemic lupus erythematosus (SLE) has been under
      intense studies during the past decade. Although the complexity inherent to
      polygenic, multifactorial diseases is challenging, several new insights have been
      obtained in the past several years using linkage and association studies of
      families containing SLE patients as well as case-control studies of populations.
      In addition, recent advances in our understanding of the human genome and
      emerging technology have been providing new tools in analyses of complex traits,
      such as SLE. An overview of our current understanding of the genetic basis of SLE
      and a brief review of findings of linkage and association studies are described
      here.

PMID- 14596885
TI  - NK cells and the tumour microenvironment: implications for NK-cell function and
      anti-tumour activity.
AB  - Although it is clear that natural killer (NK) cells have the ability to recognize
      and kill tumour cells in vitro, their potential as a highly effective treatment
      for tumours has not yet been realized in the clinical setting. Following
      activation, endogenous and adoptively transferred NK cells can be found in
      tumours. However, not all tumours are equally well-infiltrated, and many of the
      infiltrating cells do not make target-cell contact but rather reside in the
      tumour stroma. New insights into the migration of NK cells, their activation
      status and production of matrix-degrading proteases might help to overcome this
      localization defect, with implications for the treatment of human cancer.

PMID- 14596886
TI  - Tetraspanins: molecular organisers of the leukocyte surface.
AB  - Tetraspanins are a large superfamily of cell surface membrane proteins
      characterised by their four transmembrane domains. They are expressed in a wide
      variety of cell types and have functional roles in processes, such as cellular
      adhesion, motility, activation and tumour invasion. Leukocytes express </=20
      tetraspanin proteins on their surface. Tetraspanins have an exceptional ability
      to interact with a diverse array of important proteins, such as integrins,
      immunoreceptors and signalling molecules. They are thought to organise a novel
      type of cell surface membrane microdomain, which in leukocytes functions to
      regulate activation, motility and antigen presentation. The importance of
      tetraspanin microdomains in immunity is highlighted by the perturbations in the
      immune system observed in tetraspanin-deficient mice.

PMID- 14596887
TI  - The role of electrical signaling via gap junctions in the generation of fast
      network oscillations.
AB  - In recent years, several key studies have shed new light on the roles of
      electrical signaling via gap junctions between neurons in the adult brain. In
      particular, it is now clear that electrical signaling is important, if not
      essential, for the generation of a wide variety of different network interactions
      which may underlie rhythmic activity, of cognitive relevance, seen in EEG
      recordings. Two types of such rhythmic activity observed in the hippocampus both
      in vivo and in vitro are gamma frequency (30-80Hz) oscillations and ultrafast
      (>80Hz) "ripple" oscillations. Several lines of work, discussed here, show that
      gap junction-mediated signaling plays a central role in the generation of both
      these types of network activity. Recent work also now suggests that a number of
      different, anatomically discrete, gap junction-mediated networks may exist which
      could both function and be modulated independently.

PMID- 14596888
TI  - The role of metals in neurodegenerative processes: aluminum, manganese, and zinc.
AB  - Until the last decade, little attention was given by the neuroscience community
      to the neurometabolism of metals. However, the neurobiology of heavy metals is
      now receiving growing interest, since it has been linked to major
      neurodegenerative diseases. In the present review some metals that could possibly
      be involved in neurodegeneration are discussed. Two of them, manganese and zinc,
      are essential metals while aluminum is non-essential. Aluminum has long been
      known as a neurotoxic agent. It is an etiopathogenic factor in diseases related
      to long-term dialysis treatment, and it has been controversially invoked as an
      aggravating factor or cofactor in Alzheimer's disease as well as in other
      neurodegenerative diseases. Manganese exposure can play an important role in
      causing Parkinsonian disturbances, possibly enhancing physiological aging of the
      brain in conjunction with genetic predisposition. An increased environmental
      burden of manganese may have deleterious effects on more sensitive subgroups of
      the population, with sub-threshold neurodegeneration in the basal ganglia,
      generating a pre-Parkinsonian condition. In the case of zinc, there has as yet
      been no evidence that it is involved in the etiology of neurodegenerative
      diseases in humans. Zinc is redox-inactive and, as a result of efficient
      homeostatic control, does not accumulate in excess. However, adverse symptoms in
      humans are observed on inhalation of zinc fumes, or accidental ingestion of
      unusually large amounts of zinc. Also, high concentrations of zinc have been
      found to kill bacteria, viruses, and cultured cells. Some of the possible
      mechanisms for cell death are reviewed.

PMID- 14596889
TI  - Synergistic protection of PC12 cells from beta-amyloid toxicity by resveratrol
      and catechin.
AB  - beta-Amyloid peptide (beta-AP) elicits a toxic effect on neurons in vitro and in
      vivo. Many environmental factors including antioxidants, metal ions and
      proteoglycans modify beta-AP toxicity. We have investigated on PC12 cells, the
      protective effect from beta-AP (1-41) of two plant polyphenols, resveratrol and
      catechin. PC12 cells treated with 10(-6)M beta-AP (1-41) for 16h decrease the
      cell viability at 24% of the control with an IC(50) value of 1.1+/-0.14 x 10(
      8)M. Twenty-five micromolar resveratrol and 50 microM catechin protect PC12 cells
      from beta-AP (1-41) toxicity with the IC(50) value increased at 2.2+/-0.19 x 10(
      7)M and at 8.9+/-0.7 x 10(-8)M, respectively. While the protective effect is
      concentration dependent for catechin, resveratrol shows a concentration-dependent
      biphasic effect. Up to 50 microM concentration, resveratrol protects PC12 cells
      from beta-AP (1-41) toxicity. At concentration higher than 50 microM, an
      inhibitory activity on cell proliferation appears. This antiproliferative effect
      is shown also in the absence of beta-AP (1-41). Resveratrol and catechin have a
      synergistic protective action. In the presence of 50 microM catechin and 10
      microM resveratrol or 25 microM resveratrol and 10 microM catechin, the toxicity
      determined by 10(-7)M beta-AP (1-41) is almost completely abolished. Catechin is
      more effective than resveratrol in protecting PC12 cells from the toxicity of
      hydrogen peroxide. The protection from Oxygen Reactive Species (ROS) toxicity is
      concentration dependent for both resveratrol and catechin. In this case the
      protection is merely additive and the synergistic effect is not observed. These
      results demonstrate that resveratrol and catechin protect PC12 cells from beta-AP
      (1-41) toxicity and that their protective effect is synergistic. Such a
      protective effect probably is not due only to their antioxidant activity. The
      different chemical and biological activity shown by these compounds on several
      cell types and the complexity of the beta-AP (1-41) toxicity may explain the
      synergistic protective effect and suggest that the utilization of different
      compounds with synergistic activity may protect more effectively from complex
      mechanisms of toxicity.

PMID- 14596890
TI  - Hippocampal mGluR1 and consolidation of contextual fear conditioning.
AB  - The effects of post-training intra-hippocampal injections of group I mGluR
      agonists and antagonists, were examined in the contextual fear test, in rats. It
      was found that (S)-3,5-dihydroxyphenylglycine (DHPG) (a mGluR1-5 agonist)
      decreased, and (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA) (a mGluR1
      antagonist) increased fear conditioning (a freezing reaction), examined 24h after
      conditioning session. (RS)-2-Chloro-5-hydroxyphenylglycine (CHPG) (a mGluR5
      agonist), and 2-methyl-6-(phenylethynyl)pyridine hydrochloride (MPEP) (a mGluR5
      antagonist) did not cause any effect. In the immunocytochemical study, the post
      conditioning administration of AIDA decreased the c-Fos induction in the dentate
      gyrus and CA1 layer of the hippocampus proper, 2h after exposure of animals to
      the aversive context, and 24h after conditioning session. It is suggested that
      overactivation of glutamatergic transmission in the critical for memory trace
      formation structure and period of time, may result in an attenuation of memory
      consolidation. On the other hand, reduction of an exaggerated glutamatergic tone
      can facilitate learning and memory processes. The immunocytochemical study and
      factor analysis of experimental data revealed that hippocampal mGlu1 receptors
      significantly influence the memory consolidation in a way dependant on the level
      of glutamatergic activity. Furthermore, they indicate that changes of
      glutamatergic activity within brain limbic structures can affect the threshold
      for the induction of the long-term neuronal plasticity, involved in some forms of
      learning and memory.

PMID- 14596891
TI  - Cortical and striatal mu-opioid receptors are altered by gonadal hormone
      treatment but not by prenatal morphine exposure in adult male and female rats.
AB  - The cerebral cortex (CX), cingulate CX (cgCX), and striatum (STR) play an
      important role in locomotion, cognition, emotion, and reward-motivated behaviors,
      and are altered by prenatal morphine exposure. We have demonstrated that delta
      opioid receptors in the CX and STR of adult male and female rats are altered by
      prenatal morphine exposure and gonadal hormonal treatment. Because morphine binds
      with greater affinity to mu- than delta-opioid receptors, the present study
      examined the effect of prenatal morphine exposure on mu-opioid receptor density
      in the CX, cgCX, and STR of adult male and female rats using receptor
      autoradiography. In Experiment 1, three groups of adult male rats were analyzed:
      intact, gonadally intact; GNX, gonadectomized; and TP, GNX and testosterone
      propionate (TP)-treated. In Experiment 2, four groups of adult females were
      analyzed: OVX, ovariectomized; EB, OVX and estradiol benzoate (EB)-treated; P,
      OVX and progesterone (P)-treated; and EB+P, OVX and EB- and P-treated. In male
      rats, GNX and TP males had lower mu-opioid receptor densities in all three brain
      regions than gonadally intact males regardless of prenatal drug exposure. In
      female rats, OVX, EB+P-treated females had lower mu-opioid receptor density in
      the STR than OVX only females regardless of prenatal drug exposure. There were no
      drug or gonadal hormone effects in the CX or in the cgCX of female rats. Thus,
      the present study demonstrates that gonadal hormones, and not prenatal morphine
      exposure, alter the density of mu-opioid receptors in the CX, cgCX, and STR of
      adult male and female rats.

PMID- 14596892
TI  - BAX protein-immunoreactivity in midbrain neurons of Parkinson's disease patients.
AB  - Apoptosis has been implicated in the pathophysiology of Parkinson's disease (PD).
      Components of signaling pathways that initiate cell death are highly concentrated
      in vulnerable substantia nigra (SN) neurons and may therefore contribute to the
      relentless demise of dopamine cells. Here, we report the distribution and
      organizational pattern of the pro-apoptotic protein BAX in the parkinsonian
      brain. Coronal sections (60 microm) of SN material from control and PD patients
      showed identical expression of BAX-immunoreactivity (IR) in all cases examined.
      Neurons positive for BAX-IR exhibited a discrete cytoplasmic and dendritic
      labeling that was conspicuously interspersed with previously unrecognized axonal
      spheroid-like inclusions. Direct comparisons revealed a difference in the
      aggregation of BAX-rich inclusions, with the parkinsonian brain containing more
      SN inclusions than control cases. BAX expression by midbrain neurons was
      confirmed by immunoblot analysis on SN extracts showing a specific band of
      approximately 21kDa, which is consistent with the known molecular weight of
      native BAX. These results suggest that apoptosis or programmed cell death may
      play an indirect role in idiopathic PD.

PMID- 14596893
TI  - Involvement of NMDA receptors in Zif/268 expression in the trigeminal nucleus
      caudalis following formalin injection into the rat whisker pad.
AB  - We investigated the involvement of N-methyl-D-aspartate (NMDA) glutamate receptor
      in the expression of the proteins Zif/268 and c-Fos elicited by painful stimuli.
      To this purpose, the effect of the administration of MK-801, an NMDA receptor
      antagonist, on Zif/268 and c-Fos expression following a noxious stimulus,
      represented by formalin injection into the whisker pad of rats, was examined in
      neurons of the trigeminal nucleus caudalis. Furthermore, the co-localization of
      formalin injection-evoked Zif/268 and c-Fos expression and subunit 1 of the NMDA
      receptor (NR1) was studied in this nucleus. Zif/268 or c-Fos immunoreactivity
      elicited by formalin injection was significantly reduced by pretreatment with MK
      801 in the superficial layer of the trigeminal nucleus caudalis; more than 40% of
      the neurons expressing Zif/268 and c-Fos in this layer were also immunolabeled by
      NR1. On the other hand, there was little effect of MK-801 administration on
      Zif/268 and c-Fos immunoreactivity in the nucleus proprius and deep lamina V of
      the trigeminal nucleus caudalis, while most neurons expressing Zif/268 or c-Fos
      in these two regions were labeled by NR1. These results point out differences
      between the superficial and deeper layers of the trigeminal nucleus caudalis in
      the involvement of NMDA receptor in the mechanisms underlying the expression of
      protein products of immediate early genes induced by painful stimuli.

PMID- 14596894
TI  - Central adaptation to chronic administration of interleukin-1beta (IL-1beta) in
      rats.
AB  - Interleukin-1beta (IL-1beta), a cytokine, has been shown to induce a number of
      central and neuroendocrine effects. Prolonged treatment with IL-1beta is
      associated with adaptive responses in feeding, body temperature and hormone
      profiles. The purpose of the present study was to see if these effects are
      accompanied by changes in hypothalamic norepinephrine (NE) and to compare it with
      the acute effects of IL-1beta. Adult male Sprague-Dawley rats were treated (i.p.)
      with 5 microg of IL-1beta once (acute) or daily for 5 consequent days (chronic).
      The control animals received an injection of the vehicle for IL-1beta (0.1% PBS
      BSA). Body weight, food intake, and rectal temperature were monitored daily. At
      the end of treatment, the animals were sacrificed, and specific areas of the
      hypothalamus were microdissected and analyzed for NE concentrations.
      Corticosterone levels were measured in the serum. Both acute and chronic IL-1beta
      treatment produced significant changes in a number of parameters. However, there
      were marked differences between the two treatment regimens. While acute treatment
      with IL-1beta increased NE concentrations in both the paraventricular nucleus and
      the median eminence (ME), chronic treatment increased NE concentrations only in
      the ME. A corresponding increase in serum corticosterone levels was observed with
      acute IL treatment. Chronic treatment with IL-1beta decreased body weight, and
      produced an initial decrease in food intake which returned to control levels by
      the fourth day of treatment. Chronic IL treatment also produced an initial
      increase in body temperature that returned to control levels by day 4. These
      results indicate that the effects of IL-1beta on central and neuroendocrine
      functions are dependent on the duration of the treatment and that the adaptive
      responses observed in feeding and body temperature after chronic IL treatment are
      accompanied by similar responses in brain NE.

PMID- 14596895
TI  - Role of dopamine D2 receptors in the striatal immediate early gene response to
      amphetamine in reserpinized rats.
AB  - The indirect dopamine agonist amphetamine has been shown to induce a patchy
      pattern of immediate early gene (IEG) expression in the rostral striatum of both
      pharmacologically intact and reserpinized rats. The available data suggest that
      stimulation of D(2) dopamine receptors may play a role in the patterning of
      amphetamine-induced IEG expression, but direct evidence is lacking. In the
      current study of reserpinized animals, we found that pretreatment with the
      selective D(2) dopamine antagonist raclopride did not block the induction of the
      IEGs Fos and Arc by amphetamine, but greatly reduced the "patchiness" of the
      induced expression. Raclopride did not induce Fos or Arc expression by itself
      under the conditions studied here. These findings suggest that although
      stimulation of D(2) receptors is not necessary for amphetamine to induce IEG
      expression in reserpinized animals, these receptors do play a critical role in
      the spatial patterning of the resulting response.

PMID- 14596896
TI  - On the trail of an elusive flux sensor.
AB  - The hexokinase PII isozyme has been implicated as an essential component of
      multiple glucose sensing pathways in the yeast Saccharomyces cerevisiae. Several
      lines of evidence suggest that the flux through this enzymatic step, but not the
      levels of substrates, cofactors or products, is the critical process detected by
      downstream sensing machinery. In spite of intensive research efforts, how the
      activity of this enzyme is translated into a quantitative signal remains an
      unresolved question.

PMID- 14596897
TI  - Archean microfossils: a reappraisal of early life on Earth.
AB  - The oldest fossils found thus far on Earth are c. 3.49- and 3.46-billion-year-old
      filamentous and coccoidal microbial remains in rocks of the Pilbara craton,
      Western Australia, and c. 3.4-billion-year-old rocks from the Barberton region,
      South Africa. Their biogenicity was recently questioned and they were
      reinterpreted as contaminants, mineral artefacts or inorganic carbon aggregates.
      Morphological, geochemical and isotopic data imply, however, that life was
      relatively widespread and advanced in the Archean, between 3.5 and 2.5 billion
      years ago, with metabolic pathways analogous to those of recent prokaryotic
      organisms, including cyanobacteria, and probably even eukaryotes at the terminal
      Archean.

PMID- 14596898
TI  - Morphology of Legionella pneumophila according to their location within
      Hartmanella vermiformis.
AB  - The morphology of Legionella pneumophila grown within Hartmanella vermiformis was
      studied by electron microscopy. Different morphologies were observed, including a
      replicative form and a mature intracellular form, that had previously been
      reported in Hela cells. L. pneumophila was also detected within the cyst wall of
      the amoeba.

PMID- 14596899
TI  - Microbial diversity and prevalence of virulent pathogens in biofilms developed in
      a water reclamation system.
AB  - Bacterial biofilm is a common phenomenon in both natural and engineered systems
      which often becomes a source of contamination and microbially influenced
      corrosion. It is thought that formation of biofilm in the monoculture of several
      bacterial species is regulated by acylhomoserine lactone (AHL) quorum-sensing
      signals. In this study, we investigated the microbial diversity and existence of
      AHL-producing and AHL-degrading bacterial species in the biofilm samples from a
      water reclamation system located in a tropical environment. 16S ribosomal DNA
      sequencing analysis indicated the presence of at least 11 bacterial species,
      including the frequently encountered bacterial pathogens Pseudomonas aeruginosa
      and Klebsiella pneumoniae, and several rare pathogens. We showed that only two
      groups of isolates, belonging to P. aeruginosa and Enterobacter agglomerans,
      produced AHL signals. We also found that three bacterial isolates, i.e.,
      Agrobacterium tumefaciens XJ01, Bacillus cereus XJ08, and Ralstonia sp. XJ12,
      expressed AHL degradation enzymes. Furthermore, we showed that P. aeruginosa
      isolate HL43 was virulent against animal model Caenorhabditis elegans and
      released 2-6-fold more pyocyanin cytotoxin than P. aeruginosa strains PA01 and
      PA14, the two commonly used laboratory strains. These data indicate the
      complexity and importance of biofilm research in water reclamation.

PMID- 14596900
TI  - Rhodobacter massiliensis sp. nov., a new amoebae-resistant species isolated from
      the nose of a patient.
AB  - From the nose of a patient with aspiration pneumonia, we isolated a new bacterium
      by amoebal co-culture using Acanthamoeba polyphaga. Based on phenotypic, 16S rRNA
      and phylogenetic analysis, we show that this isolate represents a new species
      within the genus Rhodobacter and and we have named it Rhodobacter massiliensis.
      The type strain has been deposited in the Collection de l'Institut Pasteur,
      Paris, France (CIP 107725), and in the Culture Collection of the University of
      Goteborg, Sweden (CCUG 47968), as strain Framboise.

PMID- 14596901
TI  - Role of dentilisin in Treponema denticola epithelial cell layer penetration.
AB  - Treponema denticola is an oral anaerobic spirochete implicated in periodontal
      diseases. The chymotrypsin-like protease, dentilisin (PrtP), has been suggested
      to be an important virulence factor of T. denticola. In this study, we examined
      the role of dentilisin in T. denticola epithelial monolayer penetration by
      comparing the wild type and prtP mutant. Wild-type T. denticola can disrupt
      transepithelial resistance (TER) and substantially penetrate the HEp-2 cell
      layer. The prtP mutant altered the monolayer only slightly and penetrated the Hep
      2 layer in very low numbers. The membrane fraction of wild-type T. denticola is
      able to complement the prtP mutant in monolayer penetration, while the comparable
      fraction from the mutant has no such effect. Immunofluorescence studies suggested
      that wild-type T. denticola altered the TER by likely degrading the tight
      junctional proteins such as ZO-1. Cytotoxicity was not a major factor in the
      disruption of TER. The outer membrane vesicles (OMVs) of wild-type T. denticola
      also disrupted epithelial barrier function and penetrated the epithelial layers.
      Taken together, these results suggest that T. denticola penetrates the epithelial
      cell monolayers by altering cellular tight junctions.

PMID- 14596902
TI  - Anaerobic regulation of Actinobacillus actinomycetemcomitans leukotoxin
      transcription is ArcA/FnrA-independent and requires a novel promoter element.
AB  - The periodontal pathogen, Actinobacillus actinomycetemcomitans, produces a 116
      kDa leukotoxin that appears to help the bacterium evade the innate host immune
      response. The expression of leukotoxin is induced when cells are grown
      anaerobically, a condition found in the subgingival crevice. This regulation most
      likely occurs at the transcriptional stage since the levels of leukotoxin RNA are
      induced by hypoxic growth. In order to map the leukotoxin promoter element(s)
      responsible for oxygen regulation, deletion and linker-scanning mutations were
      cloned into a transcriptional reporter gene plasmid and then tested in A.
      actinomycetemcomitans grown aerobically or anaerobically. A 35-bp DNA element, at
      position -36 to -70, was found to be responsible for the repression of leukotoxin
      synthesis in aerobically grown A. actinomycetemcomitans. The sequence of this
      oxygen response element (ORE) does not match the consensus binding sites for
      known DNA binding proteins, not even Fnr or ArcA which play major roles in oxygen
      regulation in other bacteria. However, since sequence analysis alone cannot
      disprove a role for the Fnr or ArcAB pathways in leukotoxin regulation, the genes
      for the Fnr and ArcA homologues in A. actinomycetemcomitans were identified,
      mutated by targeted insertional mutagenesis and assessed for loss of oxygen
      regulation. Deletion of either fnr or arcA altered the expression of numerous A.
      actinomycetemcomitans proteins, but leukotoxin expression was still repressed by
      oxygen. These results, coupled with the promoter mutation analyses, lead to the
      conclusion that A. actinomycetemcomitans employs a novel pathway in the
      aerobic/anaerobic regulation of leukotoxin synthesis.

PMID- 14596903
TI  - Context-dependent effects of charged residues in transmembrane segments of MalF
      PhoA fusions.
AB  - Charged residues were introduced into the C-terminal transmembrane segment of a
      MalF-PhoA fusion to investigate the efficiency of the altered transmembrane
      segment to function as an export signal or a stop transfer signal. PhoA assays
      revealed that charges had negative effects when the transmembrane segment was
      part of a stop transfer signal but not when it was part of an export signal.
      Implications of this finding for the biogenesis of polytopic membrane proteins
      are discussed.

PMID- 14596904
TI  - In search of the prototype of nitric oxide synthase.
AB  - Recent identification of the prokaryotic genes related to the catalytic oxygenase
      domain of mammalian nitric oxide synthase (NOS) has led to speculations on the
      origins of the NO signaling network. NOS activity in eukaryotes relies on the
      concerted action of the oxygenase domain with an electron-donating reductase
      domain that is fused to it. A fused reductase domain is, however, absent in
      prokaryotes. Consequently, we searched bacterial genomes for homologs of the
      reductase domain and identified candidate genes. On the basis of genomic sequence
      and protein structural analysis, we here propose that sulfite reductase
      flavoprotein is a prototype of the mammalian NOS reductase domain and a
      complementing interaction partner of the bacterial NOS oxygenase protein.

PMID- 14596905
TI  - Why do mammalian mitochondria possess a mismatch repair activity?
AB  - All nucleated mammalian cells contain mitochondrial DNA, a small (approximately
      15-17 kb) circular genome found in the matrix. This molecule is present in
      multiple copies, with numbers routinely exceeding 1000 per cell. Many pathogenic
      mutations of this genome have been reported, with the vast majority being highly
      recessive. A mismatch repair activity has been recently described in mitochondria
      that shows no strand bias for correcting point mutations. What could be the
      physiological function of such an activity? Mammalian mtDNA is remarkable in
      being a patchwork of many short repeat sequences. With reference to several
      recent publications, we hypothesise that the function of this activity is to
      preserve the mitochondrial genome by repairing short loop out sequences that
      would otherwise be lost as mitochondrial DNA polymerase gamma replicates the
      mitochondrial genome.

PMID- 14596906
TI  - The formin-binding protein 17, FBP17, binds via a TNKS binding motif to
      tankyrase, a protein involved in telomere maintenance.
AB  - In acute myelogenous and lymphoid leukemias, rearrangements involving the MLL
      (mixed lineage leukemia) gene at chromosome 11q23 are frequent. The truncated MLL
      protein is fused in-frame to a series of partner proteins. We previously
      identified the formin-binding protein 17 (FBP17) as such an MLL fusion partner.
      In this study, we explored in vivo physiological interaction partners of FBP17
      using a two-hybrid assay and found tankyrase (TNKS), an ADP-ribose polymerase
      protein involved in telomere maintenance and mitogen-activated protein kinase
      signaling. We demonstrate that FBP17 binds via a special TNKS-binding motif to
      tankyrase. The physiological relevance is indicated by co-immunoprecipitation of
      endogenous proteins in 293T cells.

PMID- 14596907
TI  - A novel feature of microsatellites in plants: a distribution gradient along the
      direction of transcription.
AB  - A computer-based analysis was conducted to assess the characteristics of
      microsatellites in transcribed regions of rice and Arabidopsis. In addition, two
      mammals were simultaneously analyzed for a comparative analysis. Our analyses
      confirmed a novel plant-specific feature in which there is a gradient in
      microsatellite density along the direction of transcription. It was also
      confirmed that pyrimidine-rich microsatellites are found intensively near the
      transcription start sites, specifically in the two plants, but not in the
      mammals. Our results suggest that microsatellites located at high frequency in
      the 5'-flanking regions of plant genes can potentially act as factors in
      regulating gene expression.

PMID- 14596908
TI  - Differential sensitivity of plant and yeast MRP (ABCC)-mediated organic anion
      transport processes towards sulfonylureas.
AB  - The role of ATP-binding cassette (ABC) proteins such as multidrug resistance
      associated proteins (MRPs) is critical in drug resistance in cancer cells and in
      plant detoxification processes. Due to broad substrate spectra, specific
      modulators of these proteins are still lacking. Sulfonylureas such as
      glibenclamide are used to treat non-insulin-dependent diabetes since they bind to
      the sulfonylurea receptor. Glibenclamide also inhibits the cystic fibrosis
      transmembrane conductance regulator, p-glycoprotein in animals and guard cell ion
      channels in plants. To investigate whether this compound is a more general
      blocker of ABC transporters the sensitivity of ABC-type transport processes
      across the vacuolar membrane of plants and yeast towards glibenclamide was
      evaluated. Glibenclamide inhibits the ATP-dependent uptake of beta-estradiol 17
      (beta-D-glucuronide), lucifer yellow CH, and (2',7'-bis-(2-carboxyethyl)-5-(and-6
      )carboxyfluorescein. Transport of glutathione conjugates into plant but not into
      yeast vacuoles was drastically reduced by glibenclamide. Thus, irrespective of
      the homologies between plant, yeast and animal MRP transporters, specific
      features of plant vacuolar MRPs with regard to sensitivity towards sulfonylureas
      exist. Glibenclamide could be a useful tool to trap anionic fluorescent indicator
      dyes in the cytosol.

PMID- 14596909
TI  - MALS is a binding partner of IRSp53 at cell-cell contacts.
AB  - Insulin receptor substrate p53 (IRSp53) is a key player in cytoskeletal dynamics,
      interacting with the actin modulators WAVE2 and Mena. Here, we identified a PDZ
      protein, MALS, as an IRSp53-interacting protein using a yeast two-hybrid screen.
      A pull-down assay showed that IRSp53 and MALS interact through the PDZ domain of
      MALS and the C-terminal PDZ-binding sequence of IRSp53. Their interaction in MDCK
      cells was also demonstrated by co-immunoprecipitation. Immunocytochemistry showed
      the colocalization of IRSp53 and MALS at cell-cell contacts. Cytochalasin D
      induced the redistribution of both proteins to the cytosol. Thus, MALS is a
      partner of IRSp53 anchoring the actin-based membrane cytoskeleton at cell-cell
      contacts.

PMID- 14596910
TI  - Role of the kinase activation loop on protein kinase C theta activity and
      intracellular localisation.
AB  - Multiple protein kinase C (PKC) theta species, identified in an erythroleukaemia
      cell line, have been characterised in terms of their molecular properties and
      intracellular distribution. PKCthetas localised in the detergent-soluble cell
      fraction have an Mr of 76 kDa (theta-76) and contain Thr538 or pThr538 in the
      kinase activation loop. In contrast, PKCthetas localised in the Golgi complex
      have an Mr of 85 kDa (theta-85) and, although unphosphorylated at Thr538, are
      catalytically active. Strikingly, only theta-76 species which are
      unphosphorylated at Thr538 can undergo autocatalytic conversion to theta-85.
      Moreover, a Thr538-->Ala PKCtheta mutant is constitutively localised in the Golgi
      complex, confirming that changes in the phosphorylation state of this residue
      play a pivotal role in the overall control of catalytic properties and
      localisation of this kinase.

PMID- 14596911
TI  - The critical structural role of a highly conserved histidine residue in group II
      amino acid decarboxylases.
AB  - Glutamate decarboxylase is a pyridoxal 5'-phosphate (PLP)-dependent enzyme,
      belonging to the subset of PLP-dependent decarboxylases classified as group II.
      Site-directed mutagenesis of Escherichia coli glutamate decarboxylase, combined
      with analysis of the crystal structure, shows that a histidine residue buried in
      the protein core is critical for correct folding. This histidine is strictly
      conserved in the PF00282 PFAM family, which includes the group II decarboxylases.
      A similar role is proposed for residue Ser269, also highly conserved in this
      group of enzymes, as it provides one of the interactions stabilising His241.

PMID- 14596913
TI  - Plant PIP2-dependent phospholipase D activity is regulated by phosphorylation.
AB  - Phospholipase D (PLD) forms the major family of phospholipases that was first
      discovered and cloned in plants. In this report we have shown, for the first
      time, that C2 phosphatidylinositol-4,5-bisphosphate (PIP2)-dependent PLD(s) from
      5 day hypocotyls of Brassica oleracea associated with plasma membrane is
      covalently modified-phosphorylated. Pre-incubation of the plasma membrane
      fraction with acid phosphatase resulted in concentration-dependent inhibition of
      PIP2-dependent PLD activity. Using matrix-assisted laser desorption/ionization
      time of flight mass spectrometry of tryptic in-gel digests, the BoPLDgamma(1,2)
      isoform was identified. Comparing the spectra of the proteins obtained from the
      plasma membrane fractions treated and non-treated with acid phosphatase, three
      peptides differing in the mass of the phosphate group (80 Da) were revealed:
      TMQMMYQTIYK, EVADGTVSVYNSPR and KASKSRGLGK which possess five potential Ser/Thr
      phosphorylation sites. Our findings suggest that a
      phosphorylation/dephosphorylation mechanism may be involved in the regulation of
      plant PIP2-dependent PLDgamma activity.

PMID- 14596912
TI  - The protein kinase kin1, the fission yeast orthologue of mammalian MARK/PAR-1,
      localises to new cell ends after mitosis and is important for bipolar growth.
AB  - The kin1 protein kinase of the fission yeast Schizosaccharomyces pombe is a
      member of the PAR-1/MARK (partitioning-defective 1/microtubule-associated
      protein/microtubule affinity-regulating kinase) family important in eukaryotic
      cell polarity and cytoskeletal dynamics. We show here that kin1 plays a role in
      establishing the characteristic rod-shaped morphology of fission yeast. Cells in
      which kin1 was deleted are viable but are impaired in growth, and are rounded at
      one end or both ends. They are monopolar because after mitosis they fail to
      activate bipolar growth, and are delayed in cytokinesis, resulting in a high
      proportion of septated cells often with multiple septa. This phenotype can be
      partially rescued by heterologous expression of human MARKs, which restore
      bipolar growth in most cells, but do not correct the delay in cytokinesis. Using
      chromosomal epitope tagging, we show that kin1p localises to the cell ends,
      except during mitosis when it disappears from cell ends. After mitosis, kin1p
      first reappears at the new cell end. Overexpression of kin1 results in a loss of
      polarity, with partially or fully rounded cells. From these results we suggest
      that kin1 is required to direct the growth machinery to the cell ends.

PMID- 14596914
TI  - Physical and functional interaction of the Werner syndrome protein with poly-ADP
      ribosyl transferase.
AB  - Werner's syndrome is a rare disease of premature ageing. The WRN gene product
      defective in this disorder belongs to the RecQ helicase family and is thought to
      be involved in DNA metabolism. Another protein, which plays an important role in
      both DNA replication and repair, is the poly-ADP ribosyl transferase. Here we
      demonstrate an interaction of these two proteins resulting in ADP-ribosylation of
      the WRN protein. These results imply that WRN is involved in DNA replication and
      in DNA repair.

PMID- 14596915
TI  - Genomic organization and transcription of the human retinol dehydrogenase 10
      (RDH10) gene.
AB  - A cDNA clone up-regulated in hydraulic lung edema in rabbit showed high
      similarity with human RDH10 mRNA, which encodes a protein involved in retinoic
      acid metabolism. We defined the organization of the human gene, which includes a
      unique transcriptional start site, a coding region with six translated exons and
      a 3' untranslated region containing at least two used polyadenylation sites. The
      two poly(A) signals are responsible for the production of the 3 and 4 kb RDH10
      mRNA isoforms detected in several human tissues and cell lines.

PMID- 14596916
TI  - Methylation at CpG islands in intron 1 of EGR2 confers enhancer-like activity.
AB  - We previously demonstrated several lines of evidence indicating that early growth
      response 2 (EGR2) functions as a tumor suppressor, partly on the basis that its
      expression was often decreased in human tumors and cancer cell lines. Here we
      report a possible molecular mechanism to account for down-regulation of EGR2 in
      tumor cells. Although no genetic mutations in the gene or alterations in
      methylation status of its promoter were detected, we found a high degree of
      methylation at CpG islands in intron 1 of EGR2 in cell lines that were expressing
      this gene at a high level. Moreover, reporter gene experiments revealed that
      methylated intron 1 had somehow conferred enhancer-like activity. The data imply
      the existence of a previously unsuspected mechanism of gene expression
      regulation.

PMID- 14596917
TI  - The ubiquitin-protein ligase activity of Hdm2 is inhibited by nucleic acids.
AB  - The proto-oncoprotein Hdm2 is a member of the RING finger-type family of
      ubiquitin-protein ligases E3. The RING finger domain is assumed to mediate the
      specific interaction of an E3 with its cognate ubiquitin-conjugating enzyme E2,
      which catalyzes the covalent attachment of ubiquitin to substrate proteins. In
      addition, the RING finger domain of Hdm2 is involved in Hdm2 homooligomer
      formation and has the capacity to bind to RNA in a sequence-specific manner. Here
      we report that interaction with nucleic acids interferes with both Hdm2/Hdm2
      complex formation and auto-ubiquitination of Hdm2 in vitro. Furthermore, although
      binding of Hdm2 to the tumor suppressor p53 is not inhibited by nucleic acids,
      Hdm2-mediated ubiquitination of p53 is significantly decreased. Taken together,
      these results provide the first example of an E3 whose activity can be regulated
      by direct interaction with nucleic acids.

PMID- 14596918
TI  - Proteasome-dependent decrease in Akt by growth factors in vascular smooth muscle
      cells.
AB  - Akt is activated by growth factors to regulate various aspects of vascular smooth
      muscle cell function. Platelet-derived growth factor (PDGF) and insulin-like
      growth factor-1 activated Akt in vascular smooth muscle cells with a rapid
      reduction of total Akt protein that lasted for several hours. The downregulation
      of Akt required phosphatidylinositol 3-kinase activity, but not intrinsic Akt
      activity. The downregulation of Akt was abrogated by MG-132, a proteasome
      inhibitor, but not by inhibitors of calpain or cathepsins. Akt was found in
      ubiquitin immune complex after PDGF treatment. Proteasome-dependent degradation
      of Akt may provide a counter-regulatory mechanism against overactivation of Akt.

PMID- 14596919
TI  - Dab2 links CIN85 with clathrin-mediated receptor internalization.
AB  - CIN85 is a multidomain scaffold protein involved in downregulation of receptor
      tyrosine kinases. Here we show that disabled-2 (Dab2), an endocytic adaptor
      molecule implicated in clathrin-coat assembly, associates with CIN85 in mammalian
      cells. All three SH3 domains of CIN85 were able to bind to the PKPAPR peptide in
      the carboxyl-terminal part of Dab2, possibly enabling CIN85 to simultaneously
      interact with multiple Dab2 molecules. CIN85 association with Dab2 is essential
      for its recruitment to clathrin coat and appears to be modulated by growth factor
      stimulation. Dab2 and clathrin dissociated from CIN85 following growth factor
      treatment, enabling other molecules, such as Cbl, to bind to CIN85. Taken
      together, our data indicate a dynamic interplay between CIN85 and its effectors
      during endocytosis of receptor tyrosine kinases.

PMID- 14596920
TI  - Sodium butyrate inhibits angiogenesis of human intestinal microvascular
      endothelial cells through COX-2 inhibition.
AB  - We examined the effect of sodium butyrate on in vitro angiogenesis and
      cyclooxygenase (COX) expression using primary cultures of human intestinal
      microvascular endothelial cells (HIMEC). Butyrate inhibited VEGF-induced cellular
      proliferation, transmigration and tube formation of HIMEC. Butyrate also
      inhibited COX-2 expression as well as prostaglandin (PG)E2 and PGI2 production,
      and administration of PGI2 analog partially reversed the effect of butyrate on
      HIMEC angiogenesis. These results indicate that sodium butyrate inhibits HIMEC
      angiogenesis through down-regulation of COX-2 expression and PG production, and
      suggest that anti-angiogenic mechanisms may also be involved in the inhibitory
      effect of sodium butyrate on tumor growth.

PMID- 14596921
TI  - Depicting a protein's two faces: GPCR classification by phylogenetic tree-based
      HMMs.
AB  - Related proteins with similar biological functions generally share common
      features, allowing us to extract the common sequence features. These common
      features enable us to build statistical models that can be used to classify
      proteins, to predict new members, and to study the sequence-function relationship
      of this protein function group. Although evolution underlies the basis of
      multiple sequence analysis methods, most methods ignore phylogenetic
      relationships and the evolutionary process in building these statistical models.
      Previously we have shown that a phylogenetic tree-based profile hidden Markov
      model (T-HMM) is superior in generating a profile for a group of similar
      proteins. In this study we used the method to generate common features of G
      protein-coupled receptors (GPCRs). The profile generated by T-HMM gives high
      accuracy in GPCR function classification, both by ligand and by coupled G
      protein.

PMID- 14596922
TI  - Individual substitution analogs of Mel(12-26), melittin's C-terminal 15-residue
      peptide: their antimicrobial and hemolytic actions.
AB  - Residues 1-9 of M(12-26) (GLPALISWIKRKRQQ-NH2), the C-terminal 15-residue segment
      of melittin, were substituted individually to change the hydropathicities in
      these positions. Antimicrobial and hemolytic activities of these peptides were
      determined. The results showed increased antimicrobial activities with increased
      hydrophobicities at almost all the positions studied. The effects at positions 2,
      5, 8 and 9 were significant while the effects at the other positions were small.
      These two groups of residues were located on the opposite faces of the alpha
      helix. In other words, the hydrophobicities of the two faces were favorable, but
      one face (the more favorable face) contributed more to the antimicrobial
      activities than the other (the less favorable face). The hydrophobicity, not the
      amphipathicity, seems to be crucial for antimicrobial activity. In contrast, the
      hydrophobicity of one face was favorable but the other was unfavorable for the
      hemolytic activity, indicating that the amphipathicity may be important for
      hemolysis. Interestingly, the more favorable face for antimicrobial activity was
      located opposite to the favorable face for hemolytic activity, indicating the
      direction of the hydrophobic face for the antimicrobial activity and direction of
      the amphipathicity for the hemolytic activity were also important.

PMID- 14596923
TI  - Crystal structure of the dimeric unswapped form of bovine seminal ribonuclease.
AB  - Bovine seminal ribonuclease is a unique case of protein dimorphism, since it
      exists in two dimeric forms, with different biological and kinetic behavior,
      which interconvert into one another through three-dimensional swapping. Here we
      report the crystal structure, at 2.2 A resolution, of the unswapped form of
      bovine seminal ribonuclease. Besides completing the structural definition of
      bovine seminal ribonuclease conformational dimorphism, this study provides the
      structural basis to explain the dependence of the enzyme cooperative effects on
      its swapping state.

PMID- 14596924
TI  - The 'PINIT' motif, of a newly identified conserved domain of the PIAS protein
      family, is essential for nuclear retention of PIAS3L.
AB  - PIAS proteins, cytokine-dependent STAT-associated repressors, exhibit intrinsic
      E3-type SUMO ligase activities and form a family of transcriptional modulators.
      Three conserved domains have been identified so far in this protein family, the
      SAP box, the MIZ-Zn finger/RING module and the acidic C-terminal domain, which
      are essential for protein interactions, DNA binding or SUMO ligase activity. We
      have identified a novel conserved domain of 180 residues in PIAS proteins and
      shown that its 'PINIT' motif as well as other conserved motifs (in the SAP box
      and in the RING domain) are independently involved in nuclear retention of
      PIAS3L, the long form of PIAS3, that we have characterized in mouse embryonic
      stem cells.

PMID- 14596925
TI  - Regulation of the ABA-sensitive Arabidopsis potassium channel gene GORK in
      response to water stress.
AB  - The phytohormone abscisic acid (ABA) regulates many stress-related processes in
      plants. In this context ABA mediates the responsiveness of plants to
      environmental stresses such as drought, cold or salt. In response to water
      stress, ABA induces stomatal closure by activating Ca2+, K+ and anion channels in
      guard cells. To understand the signalling pathways that regulate these turgor
      control elements, we studied the transcriptional control of the K+ release
      channel gene GORK that is expressed in guard cells, roots and vascular tissue.
      GORK transcription was up-regulated upon onset of drought, salt stress and cold.
      The wilting hormone ABA that integrates responses to these stimuli induced GORK
      expression in seedlings in a time- and concentration-dependent manner and this
      induction was dependent on extracellular Ca2+. ABA-responsive expression of GORK
      was impaired in the ABA-insensitive mutants abi1-1 and abi2-1, indicating that
      these protein phosphatases are regulators of GORK expression. Application of ABA
      to suspension-cultured cells for 2 min followed by a 4 h chase was sufficient to
      manifest transcriptional activation of the K+ channel gene. As predicted for a
      process involved in drought adaptation, only 12-24 h after the release of the
      stress hormone, GORK mRNA slowly decreased. In contrast to other tissues, GORK
      expression as well as K+(out) channel activity in guard cells is ABA insensitive,
      allowing the plant to adjust stomatal movement and water status control
      separately.

PMID- 14596926
TI  - 12(S)-Hydroxyeicosatetraenoic acid induces cAMP production via increasing
      intracellular calcium concentration.
AB  - We have found that a 12-lipoxygenase metabolite of arachidonic acid, 12(S)
      hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (12-HETE), induces cAMP production in
      human normal fibroblast TIG-1 cells. This phenomenon was not observed in other
      cells tested including human embryonic kidney HEK293 cells. We have speculated
      that this specific response might be influenced by the kinds of isoform of
      adenylyl cyclase (AC) present in cells. We found that TIG-1 cells specifically
      expressed type VIII AC. As type VIII AC is known to be activated by an increase
      of calcium concentration, we determined the change of intracellular Ca2+
      concentration after the addition of 12-HETE. It was elevated not only in TIG-1
      cells, but also HEK293 cells, which did not respond to 12-HETE to produce cAMP.
      The addition of a calcium ionophore elevated the concentration of intracellular
      cAMP in TIG-1 cells, but it was without effect in HEK293 cells. To show that the
      expression of this particular isoform of AC is responsible for the positive
      response to 12-HETE, we transfected this AC isoform into HEK293 cells. The type
      VIII AC-transfected cells, in contrast to the mock-transfected ones, became very
      responsive to 12-HETE to produce cAMP. Taken all together the data would strongly
      suggest that 12-HETE specifically activates type VIII AC via increasing
      intracellular Ca2+ concentration.

PMID- 14596927
TI  - Activation of ryanodine receptor/Ca2+ release channels downregulates CD38 in the
      Namalwa B lymphoma.
AB  - CD38 is a multifunctional ectoenzyme that catalyses formation of cyclic ADP
      ribose (cADPr), a second messenger that opens ryanodine receptor (RyR) Ca2+
      channels. Despite its importance in signal transduction processes, little is
      known about the mechanisms regulating CD38 expression levels. In the current
      study, ryanodine stimulation of Ca2+ release in Namalwa cells decreased both CD38
      protein abundance and cyclase activity. Reductions in cyclase activity were
      prevented by RyR antagonists, by lysosomal blockers, though not by calpain or
      proteasomal inhibitors. These findings indicate a novel negative feedback
      mechanism between RyR channel activity and CD38 abundance acts in cADPr signal
      transduction.

PMID- 14596928
TI  - Oxidative DNA damage by hyperglycemia-related aldehydes and its marked
      enhancement by hydrogen peroxide.
AB  - Increased risks of cancers and oxidative DNA damage have been observed in
      diabetic patients. Many endogenous aldehydes such as 3-deoxyglucosone and
      glyceraldehyde (GA) increase under hyperglycemic conditions. We showed that these
      aldehydes induced Cu(II)-mediated DNA damage, including 8-oxo-7,8-dihydro-2'
      deoxyguanosine (8-oxodG) formation. GA had the strongest ability to damage DNA,
      and addition of low concentrations of H2O2 markedly enhanced the DNA damage. GA
      significantly increased 8-oxodG formation in human cultured cells (HL-60), and
      H2O2 enhanced it. We conclude that oxidative DNA damage by hyperglycemia-related
      aldehydes, especially GA, and marked enhancement of DNA damage by H2O2 may
      participate in diabetes-associated carcinogenesis.

PMID- 14596929
TI  - The Wilms' tumour suppressor protein, WT1, undergoes CRM1-independent
      nucleocytoplasmic shuttling.
AB  - The Wilms' tumour suppressor gene (WT1) encodes a zinc finger-containing nuclear
      protein essential for kidney and urogenital development. Initially considered a
      transcription factor, there is mounting evidence that WT1 has a role in post
      transcriptional processing. Using the interspecies heterokaryon assay, we have
      demonstrated that WT1 can undergo nucleocytoplasmic shuttling. We have also
      mapped the region responsible for nuclear export to residues 182-324. Our data
      add further complexity to the role of WT1 in transcriptional and post
      transcriptional regulation.

PMID- 14596930
TI  - Molecular and catalytic properties of a peroxiredoxin-glutaredoxin hybrid from
      Neisseria meningitidis.
AB  - A hybrid protein from Neisseria meningitidis, which contains both a peroxiredoxin
      and a glutaredoxin domain, has been isolated. The enzyme was active in the
      reduction of various peroxides and dehydroascorbate in the presence of reduced
      glutathione. These findings suggest that both the peroxiredoxin and glutaredoxin
      domains are biochemically active in the fusion. Moreover, when expressed
      separately, the glutaredoxin domain was catalytically active and the
      peroxiredoxin domain possessed a weak activity when supplemented with exogenous
      glutaredoxin.

PMID- 14596931
TI  - Pertussis toxin-sensitive Galphai protein and ERK-dependent pathways mediate
      ultrasound promotion of osteogenic transcription in human osteoblasts.
AB  - Bone cells respond to mechanical stimulation via mechanoreceptors and convert
      biophysical stimulation into biochemical signals that alter gene expression and
      cellular adaptation. Pulsed acoustic energy treatment raises membrane potential
      and induces osteogenic activity. How membrane-bound osteoblast mechanoreceptors
      convert physical ultrasound (US) stimuli into osteogenic responses is not fully
      understood. We demonstrated that low-intensity pulsed US treatment (200-micros
      pulse, 1 kHz, 30 mW/cm2) elevated Cbfa1/Runx2 mRNA expression and progressively
      promoted osteocalcin mRNA expression in human osteoblasts. Pretreatment with
      pertussis toxin (PTX), but not with cholera toxin, suppressed US-augmented
      osteogenic transcription. This indicated that Gi proteins, but not Gs proteins,
      were involved in US promotion of osteogenic transcription. Further studies
      demonstrated US treatment could rapidly increase PTX-sensitive Galphai protein
      levels and subsequently enhanced phosphorylation of extracellular signal
      regulated kinase (ERK). PTX pretreatment significantly reduced US promotion of
      ERK activation. Moreover, inhibition of ERK activity by PD98059 suppressed US
      augmentation of Cbfa1/Runx2 and osteocalcin mRNA expression. Membranous Galphai
      proteins and cytosolic ERK pathways acted as potent mechanosensitive signals in
      the response of osteoblasts to pulsed US stimulation.

PMID- 14596932
TI  - Structure-activity relationship for extracellular block of K+ channels by
      tetraalkylammonium ions.
AB  - External tetraalkylammonium ion binding to potassium channels is studied using
      microscopic molecular modelling methods and the experimental structure of the
      KcsA channel. Relative binding free energies of the KcsA complexes with Me4N+,
      Et4N+, and n-Pr4N+ are calculated with the molecular dynamics free energy
      perturbation approach together with automated ligand docking. The four-fold
      symmetry of the entrance cavity formed by the Tyr82 residues is found to provide
      stronger binding for the D2d than for the S4 conformation of the ligands. In
      agreement with experiment the Et4N+ blocker shows several kcal/mol better binding
      than the other tetraalkylammonium ions.

PMID- 14596933
TI  - Differential lipid affinity of xenobiotics and natural compounds.
AB  - Octanol-1/water partitioning currently provides the most widely used model system
      to simulate both phospholipid target lipids and triglyceride storage lipids. A
      differentiation between the two lipid classes is now achieved by making use of a
      water-induced lipid phase separation. Coefficients (K(TG/PC)) for partitioning
      between trioleoylglycerol (TG) and phosphatidylcholine (PC) were determined for
      20 xenobiotics and two biological lipids. K(TG/PC) values are related to KOW
      through the relationship, log K(TG/PC)=0.33 log KOW-1.078. The present results
      will allow better predictions on whether drugs and xenobiotics are
      bioaccumulated, degraded or reach toxicity-related sites. In addition,
      applications to natural lipophilic compounds and disease-related proteins are
      discussed.

PMID- 14596934
TI  - Allosteric enzymes as biosensors for molecular diagnosis.
AB  - Biosensors are hybrid analytical devices that amplify signals generated from the
      specific interaction between a receptor and the analyte, through a biochemical
      mechanism. Biosensors use tissues, whole cells, artificial membranes or cell
      components like proteins or nucleic acids as receptors, coupled to a
      physicochemical signal transducer. Allosteric enzymes exhibit a catalytic
      activity that is modulated by specific effectors, through binding to receptor
      sites that are distinct from the active site. Several enzymes, catalyzing easily
      measurable reactions, have been engineered to allosterically respond to specific
      ligands, being themselves the main constituent of new-generation biosensors. The
      molecular basis, robustness and application of allosteric enzymatic biosensing
      are revised here.

PMID- 14596935
TI  - Rescue of functional DeltaF508-CFTR channels by co-expression with truncated CFTR
      constructs in COS-1 cells.
AB  - The most frequent mutant variant of the cystic fibrosis transmembrane conductance
      regulator (CFTR), DeltaF508-CFTR, is misprocessed and subsequently degraded in
      the endoplasmic reticulum. Using the patch-clamp technique, we showed that co
      expressions of DeltaF508-CFTR with the N-terminal CFTR truncates containing bi
      arginine (RXR) retention/retrieval motifs result in a functional rescue of the
      DeltaF508-CFTR mutant channel in COS-1 cells. This DeltaF508-CFTR rescue process
      was strongly impaired when truncated CFTR constructs possessed either the
      DeltaF508 mutation or arginine-to-lysine mutations in RXRs. In conclusions, our
      data demonstrated that expression of truncated CFTR constructs could be a novel
      promising approach to improve maturation of DeltaF508-CFTR channels.

PMID- 14596936
TI  - PKCdelta inhibits PKCalpha-mediated activation of phospholipase D1 in a manner
      independent of its protein kinase activity.
AB  - The regulation of phospholipase D1 (PLD1) by protein kinase C (PKC) isoforms was
      analyzed in human melanoma cell lines. 12-O-Tetradecanoylphorbol-13-acetate (TPA)
      induced PLD1 activation was suppressed by the introduction of PKCdelta as well as
      its kinase-negative mutant in MeWo cells, which contain PKCalpha but lack
      PKCbeta. PLD activity was not affected by PKCdelta in G361 cells, which have
      PKCbeta but are deficient in PKCalpha. In MeWo cells introduced by PKCalpha and
      PLD1, the association of these proteins was observed, which was enhanced by the
      TPA treatment. In cells overexpressing PKCdelta in addition to PKCalpha and PLD1,
      TPA treatment increased the association of PKCdelta and PLD1, while it attenuated
      the association of PKCalpha and PLD1. These results indicate that PKCdelta
      inhibits TPA-induced PLD1 activation mediated by PKCalpha through the association
      with PLD1.

PMID- 14596937
TI  - Spectral tuning of obelin bioluminescence by mutations of Trp92.
AB  - The Ca(2+)-regulated photoprotein obelin was substituted at Trp92 by His, Lys,
      Glu, and Arg. All mutants fold into stable conformations and produce bimodal
      bioluminescence spectra with enhanced contribution from a violet emission. The
      W92R mutant has an almost monomodal bioluminescence (lambdamax=390 nm) and
      monomodal fluorescence (lambdamax=425 nm) of the product. Results are interpreted
      by an excited state proton transfer mechanism involving the substituent side
      group and His22 in the binding cavity.

PMID- 14596938
TI  - The immunosuppressant FTY720 is phosphorylated by sphingosine kinase type 2.
AB  - The potent immunosuppressive drug FTY720, a sphingosine analog, induces
      redistribution of lymphocytes from circulation to secondary lymphoid tissues.
      FTY720 is phosphorylated in vivo and functions as an agonist for four G-protein
      coupled sphingosine-1-phosphate receptors. The identity of the kinase that
      phosphorylates FTY720 is still not known. Here we report that although both
      sphingosine kinase type 1 (SphK1) and type 2 (SphK2) can phosphorylate FTY720
      with low efficiency, SphK2 is much more effective than SphK1. FTY720 inhibited
      phosphorylation of sphingosine catalyzed by SphK2 to a greater extent than it
      inhibits SphK1. Thus, SphK2 may be the relevant enzyme that is responsible for in
      vivo phosphorylation of FTY720.

PMID- 14596939
TI  - Photoconversion of matrix targeted GFP enables analysis of continuity and
      intermixing of the mitochondrial lumen.
AB  - We establish photoconversion of green fluorescent protein (GFP) as an optical
      'highlighter' to investigate the continuity of the mitochondrial matrix in living
      budding yeast (Saccharomyces cerevisiae). Photoconversion of GFP resulting in a
      marked shift of the absorption and emission spectra to longer wavelengths is
      elicited, under low oxygen conditions, by irradiation with blue light.
      Photoconversion induced a several 100-fold increase in red fluorescence of matrix
      targeted GFP without affecting cell viability. The color changing facilitates
      simple and effective regional optical marking in a conventional fluorescence
      microscope. We found the mitochondrial compartment of S. cerevisiae to generally
      consist of one luminally continuous large part and occasionally some additional
      smaller fragments. Separated fragments fuse within a few minutes to the large
      part, resulting in a rapid intermixing of the entire mitochondrial matrix
      compartment. In Deltafis1 and Deltadnm1 mutants restricted in outer membrane
      fission, the mitochondria are still luminally continuous, suggesting a tight
      coupling of inner and outer membrane fissions. Matrix constrictions frequently
      occurring in wild type cells as well as in Deltafis1 and Deltadnm1 mutants do not
      interfere with luminal continuity.

PMID- 14596940
TI  - Arginine kinase overexpression improves Trypanosoma cruzi survival capability.
AB  - Arginine kinase catalyzes the reversible transphosphorylation between adenosine
      diphosphate (ADP) and phosphoarginine, which is involved in temporal and spatial
      adenosine triphosphate (ATP) buffering. Here we demonstrate that the homologous
      overexpression of the Trypanosoma cruzi arginine kinase improves the ability of
      the transfectant cells to grow and resist nutritional and pH stress conditions.
      The stable transfected parasites showed an increased cell density since day 10 of
      culture, when the carbon sources became scarce, which resulted 2.5-fold higher
      than the control group on day 28. Additional stress conditions were also tested.
      We propose that arginine kinase is involved in the adaptation of the parasite to
      environmental changes.

PMID- 14596941
TI  - Kinetic analysis of human topoisomerase IIalpha and beta DNA binding by surface
      plasmon resonance.
AB  - Topoisomerase IIbeta binding to DNA has been analysed by surface plasmon
      resonance for the first time. Three DNA substrates with different secondary
      structures were studied, a 40 bp oligonucleotide, a four way junction and a 189
      bp bent DNA fragment. We also compared the DNA binding kinetics of both human
      topoisomerase isoforms under identical conditions. Both alpha and beta isoforms
      exhibited similar binding kinetics, with average equilibrium dissociation
      constants ranging between 1.4 and 2.9 nM. We therefore conclude that neither
      isoform has any preference for a specific DNA substrate under the conditions used
      in these experiments.

PMID- 14596942
TI  - Isolation of delta-missulenatoxin-Mb1a, the major vertebrate-active spider delta
      toxin from the venom of Missulena bradleyi (Actinopodidae).
AB  - The present study describes the isolation and pharmacological characterisation of
      the neurotoxin delta-missulenatoxin-Mb1a (delta-MSTX-Mb1a) from the venom of the
      male Australian eastern mouse spider, Missulena bradleyi. This toxin was isolated
      using reverse-phase high-performance liquid chromatography and was subsequently
      shown to cause an increase in resting tension, muscle fasciculation and a
      decrease in indirect twitch tension in a chick biventer cervicis nerve-muscle
      bioassay. Interestingly, these effects were neutralised by antivenom raised
      against the venom of the Sydney funnel-web spider Atrax robustus. Subsequent
      whole-cell patch-clamp electrophysiology on rat dorsal root ganglion neurones
      revealed that delta-MSTX-Mb1a caused a reduction in peak tetrodotoxin (TTX)
      sensitive sodium current, a slowing of sodium current inactivation and a
      hyperpolarising shift in the voltage at half-maximal activation. In addition,
      delta-MSTX-Mb1a failed to affect TTX-resistant sodium currents. Subsequent Edman
      degradation revealed a 42-residue peptide with unusual N- and C-terminal
      cysteines and a cysteine triplet (Cys(14-16)). This toxin was highly homologous
      to a family of delta-atracotoxins (delta-ACTX) from Australian funnel-web spiders
      including conservation of all eight cysteine residues. In addition to actions on
      sodium channel gating and kinetics to delta-ACTX, delta-MSTX-Mb1a caused
      significant insect toxicity at doses up to 2000 pmol/g. Delta-MSTX-Mb1a therefore
      provides evidence of a highly conserved spider delta-toxin from a
      phylogenetically distinct spider family that has not undergone significant
      modification.

PMID- 14596943
TI  - Alpha-conotoxins EpI and AuIB switch subtype selectivity and activity in native
      versus recombinant nicotinic acetylcholine receptors.
AB  - The Xenopus laevis oocyte expression system was used to determine the activities
      of alpha-conotoxins EpI and the ribbon isomer of AuIB, on defined nicotinic
      acetylcholine receptors (nAChRs). In contrast to previous findings on
      intracardiac ganglion neurones, alpha-EpI showed no significant activity on
      oocyte-expressed alpha3beta4 and alpha3beta2 nAChRs but blocked the alpha7 nAChR
      with an IC50 value of 30 nM. A similar IC50 value (103 nM) was obtained on the
      alpha7/5HT3 chimeric receptor stably expressed in mammalian cells. Ribbon AuIB
      maintained its selectivity on oocyte-expressed alpha3beta4 receptors but unlike
      in native cells, where it was 10-fold more potent than native alpha-AuIB, had 25
      fold lower activity. These results indicate that as yet unidentified factors
      influence alpha-conotoxin pharmacology at native versus oocyte-expressed nAChRs.

PMID- 14596944
TI  - Comparative genome analysis of Campylobacter jejuni using whole genome DNA
      microarrays.
AB  - Whole genome DNA microarrays were constructed and used to investigate genomic
      diversity in 18 Campylobacter jejuni strains from diverse sources. New algorithms
      were developed that dynamically determine the boundary between the conserved and
      variable genes. Seven hypervariable plasticity regions (PR) were identified in
      the genome (PR1 to PR7) containing 136 genes (50%) of the variable gene pool.
      When comparisons were made with the sequenced strain NCTC11168, the number of
      absent or divergent genes ranged from 2.6% (40 genes) to 10.2% (163) and in total
      16.3% (269) of the genes were variable. PR1 contains genes important in the
      utilisation of alternative electron acceptors for respiration and may confer a
      selective advantage to strains in restricted oxygen environments. PR2, 3 and 7
      contain many outer membrane and periplasmic proteins and hypothetical proteins of
      unknown function that might be linked to phenotypic variation and adaptation to
      different ecological niches. PR4, 5 and 6 contain genes involved in the
      production and modification of antigenic surface structures.

PMID- 14596945
TI  - Genetic factors in cardiovascular disease. 10 questions.
AB  - The common forms of cardiovascular disease (CVD) have a complex etiology,
      involving multiple genetic influences and important environmental interactions.
      Because of this complexity, it has proved difficult to apply the positional
      cloning approaches that have revolutionized understanding of Mendelian (single
      gene) disorders; and the understanding of the genetics of CVD and its underlying
      cause, atherosclerosis, remains poor. This review, organized into 10 broad
      questions, summarizes the understanding of the genetics of common, complex forms
      of CVD. Implications for DNA-based diagnosis, pharmacogenetics, and risk
      assessment are also discussed.

PMID- 14596946
TI  - Electrical remodeling in cardiac hypertrophy.
AB  - In recent years, electrical remodeling has emerged as an important
      pathophysiologic mechanism in many types of cardiac pathology. Because clinical
      heart disease often involves both hypertrophic and failure phenotypes,
      identification of disease-specific mechanisms is essential. This review focuses
      on mechanisms of electrical remodeling in cardiac hypertrophy, emphasizing
      transmembrane Ca2+ fluxes and Ca(2+)-responsive signaling pathways. Where
      information is available, the remodeling of hypertrophy is contrasted with what
      is known about heart failure.

PMID- 14596947
TI  - Involvement of progenitor cells in vascular repair.
AB  - Whereas the genesis of an arterial lesion is thought to be the result of
      migration and proliferation of vascular cells, recent insights into the biology
      of progenitor cells now question this concept. Specifically, endothelial and
      smooth muscle cells appear to be derived from multiple sources such as
      circulating stem and progenitor cells, as well as tissue-resident progenitor cell
      populations. These cells may engraft at sites of vascular injury and play an
      integral role in vascular repair. In this review, experimental data from in vitro
      studies, animal models, and scattered human observations are reviewed in the
      context of emerging hypotheses regarding the response to vascular injury.

PMID- 14596948
TI  - Novel approaches to identifying antiarrhythmic drugs.
AB  - Currently, device therapy with implantable cardioverter-defibrillators is the
      only proven effective therapy for sudden cardiac death. However, new insights
      into the mechanisms of ventricular fibrillation, particularly the role of dynamic
      factors that cause wave instability, are providing conceptual advances toward
      developing effective new pharmacotherapy.

PMID- 14596949
TI  - Role of stretch in activation of smooth muscle cell lineage.
AB  - Mechanical force is a critical modulator of smooth muscle (SM) function and gene
      expression. Very little is known, however, about its contribution to SM
      myogenesis. This review presents and discusses what has been learned about the
      role of mechanical force in inducing SM myogenesis and some of the signaling
      mechanisms involved in this process.

PMID- 14596950
TI  - Homeobox genes in pulmonary vascular development and disease.
AB  - Determining how the pulmonary vascular system is formed, maintained, or disrupted
      during development and disease represents a major challenge in contemporary lung
      biology. Whereas it is appreciated that cellular proliferation, differentiation,
      migration, and apoptosis need to be carefully controlled in order to attain
      pulmonary vascular homeostasis, knowledge of the underlying cellular and
      molecular mechanisms involved remains surprisingly limited. Because homeobox
      genes represent master regulators of organogenesis and tissue patterning, it is
      likely that these transcription factors play a critical role in the formation of
      blood vessels within the lung, as well as in pathologic states in which the
      highly ordered structure of the pulmonary vascular tree is compromised. The aim
      of this review is to discuss some of the known functions of homeobox genes in the
      vasculature, and to extrapolate these findings to their potential roles in
      developing and diseased pulmonary vessels.

PMID- 14596951
TI  - Research with, not on, adolescents: community-based participatory research.

PMID- 14596952
TI  - Adolescents' reasons for having sex: gender differences.

PMID- 14596953
TI  - Authority-related conformity as a protective factor against adolescent health
      risk behaviors.

PMID- 14596954
TI  - A cautionary note.

PMID- 14596955
TI  - The effectiveness of adolescent reproductive health interventions in developing
      countries: a review of the evidence.

PMID- 14596956
TI  - Reduced low birth weight for teenagers receiving prenatal care at a school-based
      health center: effect of access and comprehensive care.
AB  - PURPOSE: To examine and compare access to care, comprehensiveness of care, and
      birth outcomes for teenagers receiving prenatal care in comprehensive adolescent
      pregnancy programs (CAPPS) in two different settings: school-based vs. hospital
      based. METHODS: Retrospective sohort study using existing data sources: medical
      records and birth certificates. Using school rosters and hospital clinic
      databases, we identified pregnant adolescents < or =18 years old who delivered a
      baby between July 1, 1995 and August 30, 1997 and who received prenatal care in a
      school-based CAPP (SB-CAPP) or hospital-based CAPP (HB-CAPP). Process of care
      measures (prenatal care adequacy and comprehensive care) and outcomes (low birth
      weight) were examined by site of care. Logistic regression models were computed
      to predict the odds of low birth weight by site of prenatal care, adjusting for
      prenatal care adequacy, comprehensive care, and possible confounders including
      baseline maternal characteristics. RESULTS: Three-hundred-ninety eligible teens
      were identified. Mean age was 15.9 years, 93% were African-American, 84% in
      school, 13% had a prior birth, and 11% were cigarette smokers. Teens receiving
      care in the SB-CAPP were significantly younger and more likely to be in school
      than those in the HB-CAPP. Overall, the two groups had similar low rates of
      prenatal care adequacy, but compared with teens in the SB-CAPP, those in the HB
      CAPP were 1.5 times less likely to receive comprehensive care. Logistic
      regression analyses adjusting for baseline maternal differences showed that HB
      CAPP teens were more than three times as likely to deliver a low birth weight
      infant compared with SB-CAPP teens (AOR 3.75; 95% CI 1.05-13.36). The increased
      odds of low birth weight for HB-CAPP teens attenuated when prenatal care was
      adequate and comprehensive (AOR-HB-CAPP: 2.31, 95% CI 0.65-8.24). CONCLUSIONS:
      School-based prenatal care was associated with significantly lower odds of low
      birth weight compared with HB-CAPP care. Although selection bias may be a factor
      in this observational study, our findings suggest that these improved birth
      outcomes may be mediated through prenatal care adequacy and provision of
      comprehensive care.

PMID- 14596957
TI  - Short and long-term impact of adolescent pregnancy on postpartum contraceptive
      use: implications for prevention of repeat pregnancy.
AB  - PURPOSE: To describe patterns and changes in contraceptive use among pregnant
      adolescents in early and later postpartum compared with nonpregnant adolescents.
      METHODS: One-hundred-seventy-six pregnant and 187 nonpregnant adolescents,
      recruited through community clinics, were interviewed three times (baseline, 6
      month follow-up, 12-month follow-up) about their condom and hormonal
      contraceptive practices. Changes in contraception use and patterns of consistent
      hormonal and/or condom use were examined. Statistical analyses included General
      Estimating Equations (GEE) and multinomial regression. RESULTS: Pregnant
      adolescents increased hormonal contraceptive use from baseline to early
      postpartum, but decreased use from early postpartum to late postpartum.
      Nonpregnant adolescents did not change their hormonal contraceptive use over
      time. Neither group changed condom use over time. Pregnant adolescents were more
      likely to be consistent dual users and hormonal-only users during the 6-month
      follow-up compared with nonpregnant adolescents. These findings persisted at the
      12-month follow-up, although there was a decline in hormonal contraception use.
      CONCLUSIONS: Adolescents change their contraceptive use during the postpartum
      period. Given the slight decline in contraceptive use in late postpartum in this
      sample, more work is necessary to maintain motivation to continue these positive
      postpartum trends.

PMID- 14596958
TI  - Parental presence and adolescent reproductive health among the Nairobi urban
      poor.
AB  - PURPOSE: To investigate whether the presence of parents constitute a protective
      factor against adverse reproductive health outcomes for adolescents living in
      slums of Nairobi, Kenya. METHODS: The data come from a cross-sectional survey
      that canvassed a random sample of 4564 households representative of all Nairobi
      slums in February-June 2000. Structured questionnaires on household census,
      reproduction and adolescent health were verbally administered to household heads,
      women of reproductive ages, and adolescents, respectively. We restrict the
      analysis to a sub-sample of 788 never-married adolescent girls aged 12-19 years.
      We compare reproductive health outcomes of adolescents who live with neither
      parent, father only, mother only, and both parents. Data were analyzed using
      simple descriptive analysis and logistic regression models of three outcome
      variables: ever sexually active, ever experienced an unplanned pregnancy, and
      sexually active within the past 4 weeks. For each of the outcome variables, two
      models, one with and one without a proxy for adolescents' disorderly behavior are
      presented to establish whether parental presence affects adolescents'
      reproductive health. RESULTS: When the father is present in the household (i.e.,
      father only or both parents present), adolescent girls are 42% less likely to
      have ever had sex (p<.05), 45% less likely to have been sexually active in the
      most recent 4-week period (p<0.1), and 59% less likely to have ever experienced
      an unwanted pregnancy (p<.05) than when neither parent, or only the mother, is
      present in the household. CONCLUSIONS: In the slums of Nairobi, father's
      presence, unlike that of the mother, is associated with stronger resilience among
      adolescents. When programming for adolescents in these resource-constrained
      settings, it is important, therefore, to involve parents.

PMID- 14596959
TI  - At what price? The current state of subject payment in adolescent research.
AB  - PURPOSE: To examine how subject payment was associated with study features, such
      as investigator characteristics and project specifics, among randomly selected
      studies using adolescent subjects. METHODS: Using Psychinfo we gathered a list of
      original research studies published in 1999 that used adolescent subjects. We
      randomly selected corresponding authors and mailed confidential questionnaires on
      subject payment. We gathered complete data from 127 authors of adolescent
      research. While our main outcome was subject payment, we also examined the
      monetary value and form of the payment. Predictor variables included the
      principal investigator's demographics and professional information and the
      project's design and sample. Data were analyzed using Student's t-tests, Pearson
      correlations, and logistic regression. RESULTS: Of the studies using adolescent
      subjects, 55% (n=61) involved payment. Total payment varied (range $1 to $600,
      mean=$82.35) and the mean value per session was $26.61. Investigator
      characteristics associated with payment were a principal investigator's current
      discipline area and the decade, level and area of highest educational degree
      obtained. Funding and protocol complexity were related to payment, as was the
      sample's size, gender composition, ethnic makeup, SES distribution, and at-risk
      status. Logistic regression analyses found that researchers using payment were
      7.2 times more likely to have funding, 2.8 times more likely to work with at-risk
      youth, and for every unit increase in positive attitude toward compensation,
      there was a 1.1-fold increase in the likelihood of using payment. CONCLUSIONS: Of
      those who responded to our questionnaire, slightly more than one-half the 1999
      published studies done with adolescents used payment; however, the amount paid
      varied tremendously.

PMID- 14596960
TI  - Truth and consequences: ethics, confidentiality, and disclosure in adolescent
      longitudinal prevention research.
AB  - PURPOSE: To examine data from a natural experiment resulting from a change made
      in the confidentiality agreement midway through a randomized, longitudinal,
      controlled trial to prevent or delay adolescent alcohol use. The investigators
      explored the impact of the change on adolescents' rates of participation and
      affirmative responses to a question on suicidal thoughts. METHODS: Adolescents 12
      17 years old were administered a question on suicidal thoughts as part of a
      confidential exit interview after a general health examination with their primary
      care provider. After administration to 263 adolescents, the exit interview was
      made conditionally confidential with the remaining 181 adolescents. The revised
      consent form and protocol stipulated that researchers would reveal to appropriate
      professionals and parents any adolescent indicating suicidal thoughts. Prevalence
      estimates for the suicidal thoughts question and study participation rates were
      computed for conditions both before and after the change. RESULTS: Fewer
      adolescents responded affirmatively to the suicidal thoughts question when they
      were recruited using the revised (1%) than the original (8%) consent form and
      protocol (p=.001). The revised confidentiality agreement did not affect
      participation rates. CONCLUSIONS: Adolescents who assent to participate in
      research studies may be less likely to disclose personal information regarding
      suicidal thoughts if they know that their disclosure may result in a break in
      confidentiality. Specific guidelines are needed for conditional and unconditional
      confidentiality agreements to study mental health in adolescent longitudinal
      prevention research.

PMID- 14596961
TI  - Guidelines for adolescent health research. A position paper of the Society for
      Adolescent Medicine.

PMID- 14596962
TI  - Guidelines for adolescent health research. 1995.

PMID- 14596963
TI  - STAR gene restriction profile analysis in epidemiological typing of methicillin
      resistant Staphylococcus aureus: description of the new method and comparison
      with other polymerase chain reaction (PCR)-based methods.
AB  - A method based on restriction profile analysis of the STAR repetitive element PCR
      (STAR-RP PCR) product obtained by digestion with AluI and Tru9I was developed for
      typing methicillin resistant Staphylococcus aureus (MRSA). We evaluated a well
      defined collection of MRSA from Argentina, previously characterized by PFGE
      (pulsed field gel electrophoresis) of chromosomal SmaI digests and hybridization
      with DNA probes for probes ClaI-mecA and ClaI-Tn554. We comparatively evaluated
      STAR-RP analysis with other PCR based methods such as Inter IS256-PCR, Rep-MP3
      PCR and Coa-RP. The discriminatory power (D) of STAR-RP (0.86) was similar to
      that of PFGE (0.84) at the type level. Comparable results were obtained with
      Inter IS256 PCR (0.85) and Rep-MP3 PCR (0.80). A lower value (0.74) was obtained
      for Coa-RP. An excellent reproducibility (100%) of STAR-RP was observed. Good
      concordance between STAR-RP and other molecular typing methods was found for MRSA
      isolates (n = 39). STAR-RP typing showed 87% concordance with mecA::Tn554::PFGE,
      87% with Inter IS256 PCR and 71% with Rep-MP3 typing. STAR-RP is suggested as an
      adequate molecular typing assay for MRSA epidemiologic assessment.

PMID- 14596964
TI  - Evaluation of a rapid bacterial ATP assay for screening BAL samples from ICU
      patients submitted for quantitative bacterial cultures.
AB  - A novel application of a rapid diagnostic technique for the detection of
      significant bacterial pathogens (>/=10(4) cfu/mL) in bronchoalveolar lavage (BAL)
      samples from critically ill ventilated patients is described. This rapid
      diagnostic assay (UTIscreen, Coral Biotechnology, San Diego, CA) utilizes a
      luciferin-luciferase reaction to detect bacterial adenosine triphosphate (ATP)
      and is currently commercially available for screening bacteriuria in urine
      specimens. One hundred and twenty-eight BAL samples were examined microscopically
      with Gram's stain and tested in parallel using the bacterial ATP assay and
      standard quantitative culture. The sensitivity (Sn), specificity (Sp), positive
      predictive value (PPV), and negative predictive value (NPV) for the detection of
      bacteria >/=10(4) cfu/ml in BAL specimens for the bacterial ATP assay was 87%,
      59%, 39%, and 94%, and for the Gram's stain was 73%, 65%, 39%, and 89%,
      respectively. The diagnostic utility was improved by combining the results of
      Gram's stain/bacterial ATP assay results with Sn, Sp, PPV, and NPV of 97%, 38%,
      32%, and 97% respectively. A combined negative rapid test consisting of Gram's
      stain/bacterial ATP assay rules out significant bacteria in BAL samples with a
      high degree of certainty. Future studies are needed to clinically validate these
      observations.

PMID- 14596965
TI  - Usefulness of a combination of pulsed-field gel electrophoresis and enrichment
      culture in laboratory investigation of a foodborne outbreak due to Clostridium
      perfringens.
AB  - Clostridium perfringens is ubiquitous in nature and normally detectable in human
      stools. Therefore, it is difficult to perform specific microbiologic diagnosis in
      foodborne outbreaks, particularly when only a few cultures are detected from
      fecal specimens. Usually, it has been necessary to detect over 10(6) spores/g of
      fecal sample as a diagnostic criterion of diarrhea due to C. perfringens. A
      relatively large foodborne outbreak occurred in Osaka City, Japan in October
      2001. Although C. perfringens was suspected as the causal agent, four to seven
      days had passed after the onset of symptoms before fecal specimens were brought
      into our laboratory. The positive rate obtained by direct plating was quite low
      (13/83). We attempted to detect the organisms using enrichment culture after 75
      degrees C 20 min heat-treatment, and C. perfringens enterotoxin gene (cpe)
      positive strains were isolated from 53 of 81 samples. Pulsed-field gel
      electrophoresis (PFGE) and serotyping showed that 36 (67.9%) of these 53 strains
      had indistinguishable PFGE patterns and the same serotype, TW69. Our experience
      indicates that the enrichment culture could be useful for laboratory confirmation
      of a C. perfringens foodborne outbreak if it is used with adequate molecular
      epidemiologic methods.

PMID- 14596966
TI  - Antibody subclass profile against Leishmania braziliensis and Leishmania
      amazonensis in the diagnosis and follow-up of mucosal leishmaniasis.
AB  - Sensitivities and specificities of IgG subclasses-ELISA and IgG-indirect
      fluorescent antibody test (IFAT) against Leishmania braziliensis (Lb) and L.
      amazonensis (La) antigens were determined in 17 patients with mucosal (ML) and 19
      with muco-cutaneous (MCL) leishmaniasis. Using IFAT-IgG both antigens gave high
      sensitivities and were statistically similar, being 89.5% with La and 100% with
      Lb. Using ELISA, the highest sensitivity was achieved with total IgG for ML
      (94.7% with both antigens) and MCL (100% with both antigens). Cross-reactivity,
      observed with Chagas disease and malaria sera reduced the specificity of the IgG
      based assays, being 50 to 70% with IFAT and 40 to 70% with ELISA. An increase in
      specificity was obtained with IgG1-ELISA (90% with Lb and 100% with La). Serum
      levels of anti-Lb-IgG and IgG3 dropped 90 days after treatment. IgG subclasses
      antibody detection constitute an valuable alternative to increase the efficiency
      of sorological diagnostics of ML/MCL.

PMID- 14596967
TI  - Real-time automated polymerase chain reaction (PCR) to detect Candida albicans
      and Aspergillus fumigatus DNA in whole blood from high-risk patients.
AB  - We report the development and evaluation of a real-time PCR assay using the
      LightCycler instrument for the detection of C. albicans and A. fumigatus DNA in
      whole blood. Recently published consensus criteria for the diagnosis of invasive
      fungal infection (IFI) were used for all patient samples. Unique and published
      primer pairs were developed and assessed for sensitivity, specificity, and
      reproducibility to detect C. albicans and A. fumigatus DNA in samples spiked with
      purified DNA, and whole blood samples from 8 high-risk patients and 45 negative
      controls. The real-time assay demonstrated an analytical sensitivity of 10 fg of
      purified C. albicans and A. fumigatus DNA and was found to be specific for each
      species. The standardized approach was highly reproducible and detected C.
      albicans and A. fumigatus DNA in two patients with proven IFI and in one patient
      with a possible IFI. In addition, we report for the first time the use of
      recently published international consensus criteria for the diagnosis of IFI in
      the evaluation of a mildly invasive fungal diagnostic assay. Standardized
      clinical criteria and a more standardized approach to detect fungal DNA in less
      invasive patient samples, may permit a more reliable comparison of future
      studies. A rapid real-time detection of fungal DNA in whole blood, combined with
      standard clinical markers of response, may be more useful for monitoring patients
      at risk of developing IFI than other diagnostic methods currently available.

PMID- 14596968
TI  - Molecular analysis of isoniazid resistance in Mycobacterium tuberculosis isolates
      recovered from South Korea.
AB  - The katG, inhA and ahpC genes, in 71 isoniazid (INH)-resistant and 26 INH
      susceptible Mycobacterium tuberculosis isolates, from South Korea were examined
      by sequencing and MspI restriction enzyme analysis. Mutations in the katG 315
      alone, katG 315 plus inhA, katG 315 plus ahpC, katG 309 alone, katG 309 plus
      inhA, inhA alone, and ahpC alone, were detected in 54.9, 2.8, 1.4, 1.4, 1.4,
      19.7, and 5.6% of the 71 INH-resistant isolates, respectively. There was no
      statistically significant difference (p > 0.05) in the frequencies of these
      mutations for the INH-monoresistant compared with the multidrug-resistant
      isolates. Mutations in the katG codon 315 were associated with the high-level of
      INH resistance (MIC, >1 microg/ml), whereas the mutation in the inhA promoter
      region was associated with the low-level of INH resistance (MIC, >0.2 to 1
      microg/ml). The previously undescribed GGT-->GAT (Gly-->Asp) mutation in the katG
      codon 309 was found in two rifampin, including-multidrug-resistant isolates, but
      we cannot assess if this is predictive of INH resistance. The sensitivity and
      specificity of molecular analysis of the katG codon 315 and/or the inhA promoter
      region were 80.3 and 100%, respectively. Therefore, mutations in these regions
      are highly predictive of INH resistance in South Korea.

PMID- 14596969
TI  - Evaluation of sputum decontamination methods for Mycobacterium tuberculosis using
      viable colony counts and flow cytometry.
AB  - Continuous monitoring systems for the detection of Mycobacterium tuberculosis are
      reported to have higher contamination rates than traditional radiometric
      technologies. Multiple decontamination methods have recently been reported in an
      attempt to optimize contamination rates for these systems. In this study, several
      decontamination methods for sputum were evaluated using viable colony count and
      flow cytometry. The decontamination protocols evaluated include N-Acetyl-L
      Cysteine-Sodium Hydroxide (NALC-NaOH), modified Petroffs's method, and the Yamane
      procedure. Several parameters of the NALC-NaOH method were analyzed including
      final NaOH concentrations of 0.5-3%, NaOH exposure times of 0-30 min, and
      variations in resuspension media for the resultant pellet. All decontamination
      methods were performed on pooled and sterilized sputum seeded separately with
      either a mixture of common contaminating bacteria or M. tuberculosis H37Ra.
      Viability of organisms following decontamination was assessed by both colony
      counts and flow cytometric analysis. Flow cytometry viability assays utilized a
      combination of viability dyes and reference beads to determine viable organism
      concentrations. The results indicated that no decontamination method was clearly
      superior, however a concentration of 1-2% NaOH and an increase in the time of
      NaOH exposure to 30 min will effectively kill contaminating bacteria without
      significantly affecting the viability of M. tuberculosis H37Ra. While flow
      cytometry viability analysis did not directly correspond to viable colony counts,
      it was a useful tool for rapid viability analysis M. tuberculosis.

PMID- 14596970
TI  - Nosocomial superinfections due to linezolid-resistant Enterococcus faecalis:
      evidence for a gene dosage effect on linezolid MICs.
AB  - Resistance to linezolid among Enterococcus faecium and Enterococcus faecalis
      isolates has been reported in patients who receive a prolonged course of the
      drug. We report two cases of linezolid-resistant Enterococcus faecalis that
      occurred in patients who previously received linezolid for infections with
      vancomycin-resistant Enterococcus faecium. Both isolates had the G2576U mutation
      in the 23S rRNA previously reported in isolates of Enterococcus faecium. The
      number of gene copies mutated in the 23S rRNA correlated with the level of
      resistance.

PMID- 14596971
TI  - Contemporary evaluation of the in vitro activity and spectrum of cefdinir
      compared with other orally administered antimicrobials tested against common
      respiratory tract pathogens (2000-2002).
AB  - Cefdinir is an oral cephalosporin approved by the Food and Drug Administration in
      1997 for the treatment of acute exacerbation of chronic bronchitis, pharyngitis
      tonsillitis, community-acquired pneumonia, acute maxillary sinusitis, and
      uncomplicated skin and skin structure infections in adults and adolescents, and
      acute otitis media, pharyngitis-tonsillitis, and uncomplicated skin and skin
      structure infections in children. Although cefdinir showed similar activity to
      other cephalosporins in the early studies, very limited data has been generated
      over the last decade. In this report, we summarize the contemporary in vitro
      activity and spectrum of cefdinir in comparison to numerous other orally
      administrated antimicrobials available for treatment of community-acquired
      respiratory infections. A total of 8,326 non-duplicate recent clinical isolates,
      including Haemophilus influenzae (3,438), Moraxella catarrhalis (1,688), and
      Streptococcus pneumoniae (3,200), were collected from 35 medical centers in North
      America during 2000 through 2002, and susceptibility tested by reference broth
      microdilution methods. Pneumococcal susceptibility patterns for beta-lactams and
      macrolides were also analyzed according to the year of isolation and the age
      group of the patients. Cefdinir had the greatest activity against H. influenzae
      among the cephalosporins tested with susceptibility rates of 97.1 to 99.0%. All
      of the agents tested had complete or near complete activity against M.
      catarrhalis. Against S. pneumoniae, cefdinir and other cephalosporins showed
      similar susceptibility patterns, but improved rates were observed in 2002 (78.5
      79.4%) when compared to the previous monitored period (71.8-74.5%). This increase
      in susceptibility was mainly because of a declining the occurrence of high-level
      penicillin resistance (MIC >/=2 microg/ml) across all age groups. Macrolide
      resistance also decreased among S. pneumoniae in 2002 when compared to 2000
      through 2001; however, resistance to levofloxacin continued to increase from 0.9%
      in 2000 to 1.4% in 2002. These results indicate a significant change in emerging
      beta-lactam resistance patterns (including cefdinir) with a decrease possibly
      influenced by greater pneumococcal vaccine use in children and the elderly. These
      rates of increased susceptibility could sustain and enhance the clinical activity
      of orally administered beta-lactams such as cefdinir.

PMID- 14596972
TI  - Argentinean collaborative multicenter study on the in vitro comparative activity
      of piperacillin-tazobactam against selected bacterial isolates recovered from
      hospitalized patients.
AB  - The in vitro activity of piperacillin-tazobactam and several antibacterial drugs
      commonly used in Argentinean hospitals for the treatment of severe infections was
      determined against selected but consecutively isolated strains from clinical
      specimens recovered from hospitalized patients at 17 different hospitals from 9
      Argentinean cities from different geographic areas during the period November
      2001-March 2002. Out of 418 Enterobacteriaceae included in the Study 84% were
      susceptible to piperacillin-tazobactam. ESBLs putative producers were isolated at
      an extremely high rate since among those isolates obtained from patients with
      hospital acquired infections 56% of Klebsiella pneumoniae, 32% of Proteus
      mirabilis and 25% Escherichia coli were phenotypically considered as ESBLs
      producers Notably P.mirabilis is not considered by for screening for ESBL
      producers. ESBLs producers were 100% susceptible to imipenem and 70% were
      susceptible to piperacillin-tazobactam whereas more than 50% were resistant to
      levofloxacin. The isolates considered as amp C beta lactamase putative producers
      showed 99% susceptibility to carbapenems while 26.7% were resistant to
      piperacillin-tazobactam and 38.4% to levofloxacin. Noteworthy only 4% of the
      Enterobacteriaceae isolates were resistant to amikacin. Piperacillin-tazobactam
      was the most active agent against Pseudomonas aeruginosa isolates (MIC(90): 128
      microg/ml; 78% susceptibility) but showed poor activity against Acinetobacter spp
      (MIC(90):>256 microg/ml; 21.7% susceptibility). Only 41.7% Acinetobacter spp
      isolates were susceptible to ampicillin-sulbactam. Piperacillin-tazobactam
      inhibited 100% of Haemophilus influenzae isolates (MIC(90) < 0.25 microg/ml) but
      only 16.6% of them were ampicillin resistant. The activity of piperacillin
      tazobactam against oxacillin susceptible Staphylococcus aureus or coagulase
      negative staphylococci was excellent (MIC(90) 2 microg/ml; 100% susceptibility).
      Out of 150 enterococci 12 isolates (8%) were identified as E.faecium and only
      three isolates (2%), 2 E.faecium and 1 E.faecalis were vancomycin resistant. All
      the enterococci isolates were susceptible to linezolid. Piperacillin-tazobactam
      showed excellent activity (MIC(90) 2 microg/ml; 92% susceptibility). Regarding
      pneumococci all the isolates showed MICs of 16 microg/ml for piperacillin
      tazobactam. Among 34 viridans group streptococci only 67% were penicillin
      susceptible and 85.2% ceftriaxone susceptible whereas piperacillin-tazobactam was
      very active (MIC(90) 4 microg/ml).Piperacillin-tazobactam is therefore a very
      interesting antibacterial drug to be used, preferably in combination (IE:
      amikacin-vancomycin) for the empiric treatment of severe infections occurring in
      hospitalized patients in Argentina. Caution must be taken for infections due to
      ESBL producers considering that the inoculum effect MICs can affect MIC values.

PMID- 14596973
TI  - Daptomycin against multiple drug-resistant staphylococcus and enterococcus
      isolates in an in vitro pharmacodynamic model with simulated endocardial
      vegetations.
AB  - Daptomycin is a lipopeptide antibiotic that exhibits bactericidal activity
      against Gram-positive bacteria. In pursuit of potential clinical dosing regimens
      for endocarditis, we evaluated two, once-daily daptomycin regimens against
      multiple, drug-resistant Gram-positive pathogens. Daptomycin susceptibility was
      determined in the absence and presence of physiologic concentrations of albumin.
      An in vitro pharmacodynamic model with simulated endocardial vegetations
      incorporating protein was used to simulate regimens of daptomycin at 6 and 8
      mg/kg/day and vancomycin at 1 g every 12 h against methicillin-resistant S.
      aureus (MRSA-67 and 494) and S. epidermidis (MRSE-R227 and R617), glycopeptide
      intermediate S. aureus and S. epidermidis (GISA-992 and GISE-12333), and
      vancomycin-resistant E. faecium (VREF-SF12047 and 12366). Bacterial
      quantification occurred over 72 h. Daptomycin MIC results for study isolates in
      the absence or presence of albumin ranged from 0.125 to 4 and 1 to 8,
      respectively. Both daptomycin regimens achieved greater than 99.9% kill by 8 h
      and demonstrated greater bacterial reduction than vancomycin against all tested
      isolates at 24, 48, and 72 h (p < 0.05). Undetectable limits of bacterial
      quantification was achieved and maintained by 8 mg/kg/day against MRSA-494 and
      67, GISA-992, and VREF-590 for the study duration. Although slight regrowth was
      noted only for 6 mg/kg/day against MRSA-67, 99.9% kill was maintained throughout
      the study period without development of resistance. Pharmacodynamic profiles and
      drug exposure of daptomycin at 6 mg/kg/day corresponds to previously reported
      AUC/MIC requirements. These results suggest that 6 and 8 mg/kg/day of daptomycin
      represent potential regimens for further clinical evaluation in drug-resistant
      Gram-positive endocarditis.

PMID- 14596974
TI  - Contemporary in vitro synergy rates for aztreonam combined with newer
      fluoroquinolones and beta-lactams tested against gram-negative bacilli.
AB  - Aztreonam has been commonly used in various combinations to enhance antimicrobial
      spectrum of co-drugs and produce potential synergistic activity. Although well
      studied in vitro over 10 years ago, aztreonam combination testing has been poorly
      documented with newer or commonly used agents against contemporary isolates. All
      MIC tests (alone or in combination) used in this experiment were reference broth
      microdilution methods in checkerboard tray designs. Aztreonam was combined with
      ciprofloxacin, gatifloxacin, levofloxacin, cefepime, ceftazidime and imipenem at
      clinically relevant concentrations. Interaction categories were defined by
      established criteria. Forty strains each of Pseudomonas aeruginosa and
      Enterobacteriaceae (12 species; aztreonam MIC, 1-16 microg/ml) were tested for
      each antimicrobial combination (480 total determinations). No antagonism or
      indeterminate interactions were identified. The overall rates of synergy or
      partial synergy for aztreonam with fluoroquinolone combinations was 63.4% versus
      P. aeruginosa, greatest for aztreonam with gatifloxacin (67.5%). Interaction
      categories varied greatly among aztreonam with beta-lactam combinations.
      Aztreonam with ceftazidime or cefepime versus P. aeruginosa had 75.0 - 85.0%
      partial or complete synergy rates, but aztreonam with imipenem showed dominant
      indifference (65.0%). In contrast, aztreonam with imipenem was more likely to
      exhibit synergy (32.5%) when tested against Enterobacteriaceae. Aztreonam, often
      used as an aminoglycoside substitute in antimicrobial combinations, continues to
      demonstrate enhanced, but variable drug activity interactions for contemporary
      antimicrobial combinations when tested against recent (2002) clinical isolates.

PMID- 14596976
TI  - Historical origin of the Southern Thoracic Surgical Association.

PMID- 14596977
TI  - History of general thoracic surgery and the Southern Thoracic Surgical
      Association: the first 25 years.

PMID- 14596978
TI  - General thoracic surgery and the Southern Thoracic Surgical Association: the
      second 25 years.

PMID- 14596979
TI  - Adult cardiac surgery during the first 50 years of the Southern Thoracic Surgical
      Association.
AB  - This is a review of some of the outstanding adult cardiac surgical papers
      presented during the first 50 years of the Southern Thoracic Surgical Association
      to commemorate the 50th Anniversary meeting. Since the founding of the Southern
      Thoracic Surgical Association in 1954 there have been a total 512 adult cardiac
      surgery and great vessels papers presented, 138 from 1954 to 1970, 157 from 1971
      to 1986, and 217 from 1987 to 2002. Since 1964 most of these papers have been
      published in The Annals of Thoracic Surgery. Forty-three papers were reviewed,
      the first having been presented in 1956 and the last in 2002. Not all of the
      papers could be located but the vast majority were retrievable and reviewed. This
      paper presents a broad spectrum of adult cardiac surgery beginning with early
      pump technology, early myocardial revascularization including the Vineberg
      procedure followed by coronary bypass as we know it today, valvular surgery,
      including several papers on aortic valve homograft and autograft procedures,
      ventricular aneurysms, aortic aneurysms and aortic dissections. Evaluations of
      various valve prostheses, cardiac transplantation, mitral valve reconstruction,
      quality assurance in cardiac surgery, neurobehavioral outcome after cardiac
      surgery, endocarditis and off-pump coronary bypass surgery were reviewed. We hope
      that this article is representative of the broad spectrum of issues that have
      characterized the specialty of cardiothoracic surgery over the second half of the
      20th century and the beginning of the 21st century.

PMID- 14596980
TI  - The Southern Thoracic Surgical Association 50th anniversary celebration: the
      impact of STSA pediatric cardiothoracic surgery manuscripts on surgical practice.
AB  - BACKGROUND: Members of the Southern Thoracic Surgical Association (STSA) have
      presented important pediatric cardiothoracic surgery papers at the annual
      meetings over the last 50 years. In order to determine the influence of these
      presentations on the practice of surgery, a review was undertaken. Early papers
      were characterized by emerging advances in open-heart surgery, anatomic
      congenital heart studies, and electrophysiologic discoveries that extended life
      with pacemakers. Later years were characterized by innovative myocardial
      preservation methods, improved cardiopulmonary bypass techniques, expanded
      homograft availability, emphasis on accurate repairs, intraoperative
      transesophageal echocardiography, and cardiopulmonary transplantation. METHODS:
      All but one of the scientific programs of the annual meetings (that of 1964) were
      located. The programs were reviewed and 180 presentations were identified on
      topics in congenital heart disease, pediatric thoracic disease, and pediatric
      thoracic wall abnormalities. Of those 180 oral presentations, 155 manuscripts
      (86%) were eventually published or in press and available for critical review and
      analysis. Manuscripts were grouped by diagnosis or therapeutic intervention. We
      determined a "cumulative citation frequency" (CCF), which measures the number of
      times an article is cited in the bibliography of related papers in the universe
      of participating journals. The selected manuscripts were compared with the
      historic landmark contributions and the existing trends at the time, and the
      number of articles both by individual authors and from institutions were tallied.
      RESULTS: Grouping by authors and institutions showed that 100 of 155 pediatric
      cardiothoracic manuscripts (65%) originated from 13 institutions. The CCF for the
      20 leading articles ranged from 26 to 93. CONCLUSIONS: This historical STSA 50
      year record of pediatric cardiothoracic advances was accomplished in a milieu of
      collegial respect and camaraderie. Our annual meetings over the years have
      provided a venue for thoracic surgeons to share their ideas, innovations, and
      scientific inquiry. These contributions have significantly affected the practice
      of pediatric cardiothoracic surgery. The STSA has worked for 50 years and we
      trust that it will work for another 50 years and beyond.

PMID- 14596981
TI  - A salute to the contributions of the spouses of the Southern Thoracic Surgical
      Association on the occasion of its 50th anniversary.

PMID- 14596983
TI  - Enterococci in foods. Functional and safety aspects. Proceedings on an
      international symposium. Berlin, Germany. May 30-31, 2002.

PMID- 14596982
TI  - A brief history of the Southern Thoracic Surgical Association and a synopsis of
      the Presidential addresses.
AB  - This article contains a brief history of the Southern Thoracic Surgical
      Association since it was founded in 1953, and a synopsis of each Presidential
      Address that was available for review. Not all Addresses were available or could
      be obtained.

PMID- 14596984
TI  - Enterococci in foods--a conundrum for food safety.
AB  - Enterococci form part of the lactic acid bacteria (LAB) of importance in foods.
      They can spoil processed meats but they are on the other hand important for
      ripening and aroma development of certain traditional cheeses and sausages,
      especially those produced in the Mediterranean area. Enterococci are also used as
      human probiotics. However, they are important nosocomial pathogens that cause
      bacteraemia, endocarditis and other infections. Some strains are resistant to
      many antibiotics, but antibiotic resistance alone cannot explain the virulence of
      some of these bacteria. Virulence factors such as adhesins, invasins and
      haemolysin have been described. The role of enterococci in disease has raised
      questions on their safety for use in foods or as probiotics. Studies on the
      incidence of virulence traits among enterococcal strains isolated from food
      showed that some harbour virulence traits and generally, Enterococcus faecalis
      harbours more of them than Enterococcus faecium. Regulations in Europe stipulate
      that safety of probiotic or starter strains is the responsibility of the
      producer; therefore, each strain intended for such use should be carefully
      evaluated. For numerous questions, immediate answers are not fully available. It
      is therefore suggested that when considering an Enterococcus strain for use as a
      starter or probiotic culture, it is imperative that each particular strain should
      be carefully evaluated for the presence of all known virulence factors. Ideally,
      such strains should harbour no virulence determinants and should be sensitive to
      clinically relevant antibiotics. In general, E. faecium appears to pose a lower
      risk for use in foods, because these strains generally harbour fewer recognised
      virulence determinants than E. faecalis. Generally, the incidence of such
      virulence determinants among E. faecium strains is low, as compared to E.
      faecalis strains, probably as a result of the presence of pheromone-responsive
      plasmids.

PMID- 14596985
TI  - Taxonomy, ecology and antibiotic resistance of enterococci from food and the
      gastro-intestinal tract.
AB  - Apart from genotypic identification methods, there is a need for reliable
      conventional phenotypic identification schemes for simple and rapid determination
      of enterococcal species in food or in the gastro-intestinal tract (GIT). Only a
      limited number of enterococcal species is of importance for the ecology of the
      GIT or the food microflora, including E. faecalis, E. faecium, E. durans/hirae,
      E. gallinarum and E. casseliflavus. After genus identification the
      differentiation within these species can include, e.g. mannitol and arabinose
      fermentation and growth at 50 degrees C. Widely used commercial identification
      systems may fail to precisely identify rare species. Ecological aspects should
      also be taken into account. In the human GIT E. faecium is the most common
      species whereas in most animal species E. faecalis is at least present in the
      same amount. Especially in foods of animal origin (cheese, pork meat, beef,
      poultry meat) also E. faecalis is very frequent. This is of special interest as
      glycopeptide resistance is most often found in human clinical E. faecium strains
      as well as in E. faecium from the environment or animal samples and less frequent
      in E. faecalis strains. EU experts propose as safety criteria for probiotics in
      feed additives the exclusion of resistances or the lack of transferability. This
      proposal can also be applied to enterococci in foods. Specific resistances must
      be excluded, but transferability or acquisition of resistance (e.g. vancomycin)
      cannot be excluded per se. However, technologically used strains should differ
      from clinical strains concerning their resistance patterns and transfer rates.

PMID- 14596986
TI  - Comparison of enterococcal populations in animals, humans, and the environment--a
      European study.
AB  - The objectives of the present study were to generate knowledge of enterococcal
      populations in the food chain, by studying the population structure (in measures
      of abundance and diversity) among enterococci in different geographical regions
      and in different parts of the food chain, as well as the similarities between
      different enterococcal populations. Altogether, 2868 samples were collected from
      humans (healthy and hospitalised individuals and clinical isolates), animals
      (slaughterhouse carcasses and farm animals), and the environment (pig farms,
      sewage, and surface water) in four European countries-Sweden, Denmark, UK, and
      Spain. The samples were characterised with regard to presence and numbers of
      enterococci, and eight (for faecal samples) or 24 (for environmental samples)
      isolates per sample were phenotyped and preliminarily identified with the PhP-RF
      system. In total, more than 20,000 isolates were typed. A majority of the samples
      (77%) showed the presence of presumed enterococci. The diversities of enterococci
      in environmental samples were generally high, and also faecal samples normally
      showed presence of more than one enterococcal strain. The most common species
      found were Enterococcus faecium (33%), E. faecalis (29%), and E. hirae (24%), but
      different enterococcal populations differed in their species distribution.
      Clinical isolates, hospitalised patients, and hospital sewage in Sweden showed a
      clear dominance of E. faecalis (80%, 57%, and 54%, respectively) whereas healthy
      individuals and urban sewage contained less E. faecalis (39% and 40%,
      respectively). The species distribution among isolates from slaughterhouses
      varied between animal species and also between countries, but E. faecalis seemed
      to be mainly associated with broiler, and E. hirae with cattle and pigs. The
      results from the study have indicated a simplified method to study the diversity
      of bacterial populations. Instead of collecting many samples and analysing one or
      a few isolates per sample, it is possible to collect fewer samples and analyse
      several isolates per sample. Both approaches yielded similar information on the
      diversity of the populations. Another useful information was that since samples
      from hospital sewage, urban sewage, and manure contained enterococcal populations
      that reflected those in faecal samples of hospitalised patients, healthy humans,
      and animals, respectively, such samples may be used as pooled faecal samples and
      may replace cumbersome samplings from many individuals.

PMID- 14596987
TI  - Methods used for the isolation, enumeration, characterisation and identification
      of Enterococcus spp. 1. Media for isolation and enumeration.
AB  - Due to their significance in food, feed, environmental and clinical samples, the
      detection and enumeration of enterococci have become an important issue not only
      in daily routine but also in current research activities. Several media and
      protocols have been published for diverse purposes, but there is no single
      method, which universally meets all requirements. Depending on the nature of the
      accompanying microflora and its level, certain substrates and modifications
      thereof have to be used, taking into account various drawbacks and advantages. In
      addition to the historical applications (examination of water, different kinds of
      foods, intestinal and other clinical specimen), the detection of vancomycin
      resistant enterococci (VRE) has become an important task, since VRE have found to
      be frequently involved in nosocomial infections. Moreover, contradictory
      methodological recommendations can be found in the literature. This paper will
      give a systematic survey of the different media and methods proposed during the
      last two decades. Emphasis is placed on compositional details and on specific
      applications of the media described.

PMID- 14596988
TI  - Methods used for the isolation, enumeration, characterisation and identification
      of Enterococcus spp. 2. Pheno- and genotypic criteria.
AB  - This paper reviews the methodology applied for the identification and
      characterisation of enterococci and covers phenotypic, genotypic and phylogenetic
      techniques. Although conventional phenotypic typing schemes are useful for rapid
      and simple identification of enterococcal species for routine applications, other
      methods like standardised sodium dodecylsulfate polyacrylamide gel
      electrophoresis (SDS-PAGE), multilocus enzyme electrophoresis (MLEE),
      antimicrobial susceptibility testing, serotyping, pyrolysis mass spectrometry
      (pyMS) and vibrational spectroscopic methods allow a more in-depth
      characterisation of enterococci. Many of the recently described enterococcal
      species exhibit deviations from hitherto so-called classical enterococci with
      regard to their phenotypical properties. Therefore, genotypic methods have to be
      used to clarify their possible assignment to the genus Enterococcus. In this
      review, special emphasis is given on recently developed polymerase chain reaction
      (PCR)-based typing methods such as random amplified polymorphic DNA (RAPD),
      amplified fragment length polymorphism (AFLP), specific and random amplification
      (SARA) and modifications of PCR-ribotyping as well as pulsed-field gel
      electrophoresis (PFGE) and partial sequence analysis. The use of PCR and probes
      for genus and species identification of enterococci is also considered like the
      application of sequence data of conserved DNA regions (e.g., ribosomal
      ribonucleic acid (rRNA) genes) in the case of species identification.

PMID- 14596989
TI  - The PhenePlate system for studies of the diversity of enterococcal populations
      from the food chain and the environment.
AB  - The growing interest in ecological investigations, such as studies of the "flow"
      of bacteria through the food chain, has resulted in a great need for simple
      typing techniques for bacteria that can be used when a large number of isolates
      need to be analysed. The present study describes a simple method for biochemical
      fingerprinting of enterococci, the PhenePlate RF (PhP-RF) system. The system is
      based on a 96-well microplate containing eight sets of 11 dehydrated reagents,
      selected to have a high discriminatory power among enterococcal isolates. The PhP
      plates are inoculated easily by picking single colonies directly from the primary
      agar culture and suspending them in the first well of each row in the microplate.
      The kinetics of each reaction is evaluated by measuring the absorbance value of
      each well three times during 64 h, whereupon a biochemical fingerprint is
      calculated as the mean value for each reagent over the three readings. The PhP-RF
      method was shown to be highly reproducible, even when results were compared
      between different laboratories. The discriminatory power, measured as Simpson's
      diversity index (Di), was as high as 0.96 for all enterococci. The PhP-RF method
      could also be used as a preliminary species identification method, by comparing
      the biochemical fingerprints of unknown strains to those of a set of reference
      strains of known species. Most strains of Enterococcus faecalis, Enterococcus
      faecium and Enterococcus hirae were correctly identified using this method. We
      conclude that the PhenePlate RF system is useful for rapid typing of enterococcal
      populations, and it is especially useful as a first screening method for
      ecological studies, when many isolates per sample need to be analysed.

PMID- 14596990
TI  - Differentiation of Enterococcus faecium from Lactobacillus delbrueckii subsp.
      bulgaricus and Streptococcus thermophilus strains by PCR and dot-blot
      hybridisation.
AB  - Variations in length and sequence of the 16S/23S spacer region of Enterococcus
      faecium provided the basis for development of simple PCR and dot-blot
      hybridisation assays that enabled the differentiation of potentially probiotic
      Enterococcus faecium strains from Lactobacillus delbrueckii subsp. bulgaricus and
      Streptococcus thermophilus. Such assays may be useful for differentiation of
      yoghurt starter cultures and enterococcal strains when they are simultaneously
      present in probiotic food products.

PMID- 14596991
TI  - Glucose prevents citrate metabolism by enterococci.
AB  - Enterococcus faecalis FAIR E-239, growing on glucose plus citrate, metabolized
      citrate at pH 6.5 or 7.5, but only when glucose had been exhausted; it did not
      metabolize citrate at pH 5.5 or 8.5. When grown on citrate only, the strain
      metabolized citrate at all pH values, and two growth rates were apparent. Citrate
      was mainly metabolized during the second, much slower growth rate. Glucose also
      inhibited citrate metabolism by E. faecalis FAIR E-237 and FAIR E-259 and
      Enterococcus faecium FAIR E-338 and FAIR E-371. Glucose-grown resting cells were
      unable to metabolize citrate. Citrate-grown resting cells had a pH optimum of 4.7
      for citrate metabolism but also metabolized significant amounts of citrate at pH
      4.2 and 6.5. Resting stationary phase cells used citrate more rapidly than
      resting log phase cells. Citrate metabolism was faster at citrate levels <10 mM
      than above 10 mM. These results suggest that some form of catabolite repression
      is occurring.

PMID- 14596993
TI  - Functionality of enterococci in dairy products.
AB  - Enterococci have important implications in the dairy industry. They occur as
      nonstarter lactic acid bacteria (NSLAB) in a variety of cheeses, especially
      artisan cheeses produced in southern Europe from raw or pasteurised milk, and in
      natural milk or whey starter cultures. They play an acknowledged role in the
      development of sensory characteristics during ripening of many cheeses and have
      been also used as components of cheese starter cultures. The positive influence
      of enterococci on cheese seems due to specific biochemical traits such as
      lipolytic activity, citrate utilisation, and production of aromatic volatile
      compounds. Some enterococci of dairy origin have also been reported to produce
      bacteriocins (enterocins) inhibitory against food spoilage or pathogenic
      bacteria, such as Listeria monocytogenes, Staphylococcus aureus, Vibrio cholerae,
      Clostridium spp., and Bacillus spp. The technological application of enterocins,
      shown to be produced during cheese manufacture, led to propose enterococci as
      adjunct starter or protective cultures in cheeses. There is evidence that
      enterococci, either added as adjunct starters or present as nonstarter NSLAB,
      could find potential application in the processing of some fermented dairy
      products. Literature suggest that the complex biochemical and ecological
      phenomena explaining the technological functionality of the enterococci in dairy
      products, are still to be fully understood. Clearly, the clinical research on
      enterococci underlines also that the safety of dairy products containing
      enterococci is an issue that the industry must carefully address before
      proceeding to their application.

PMID- 14596992
TI  - Physiological and molecular aspects of bile salt response in Enterococcus
      faecalis.
AB  - Analysis of the susceptibility and the acquisition of tolerance in Enterococus
      faecalis towards bile salts showed a nearly instantaneous killing effect and
      yielded evidence for homologous tolerance as well as for cross-protections. Two
      dimensional (2-D) electrophoresis revealed 45 proteins which are amplified in
      response to the bile salt treatment. These include a set of seven proteins, the
      synthesis of which is increased not only with the bile salts but also with
      multiple sublethal stresses of various nature. Characterisation of the latter
      (called general stress proteins) showed that at least five of them are related to
      resistance to bile salts, heat, ethanol, oxidative and alkaline pH stresses and
      are probably involved in cross-protection development. On the other hand, random
      mutagenesis of E. faecalis allowed the isolation of 10 bile salt-sensitive
      mutants. Their characterisation revealed that the mutation loci corresponded to
      genes related to DNA repair, oxidative response, transcriptional regulation, dGTP
      hydrolysis, membrane composition or cell wall synthesis. Further characterisation
      of one mutant revealed that the insertion within the E. faecalis sagA gene led to
      morphology changes, to perturbations of cell division and to a decrease of the
      resistance towards several independent physicochemical stresses.

PMID- 14596994
TI  - Functionality of enterococci in meat products.
AB  - The presence of enterococci in meat fermentation is a constant as reported in the
      literature. Despite the concern about pathogenicity of enterococci, recent
      studies point out that food and meat enterococci, especially Enterococcus faecium
      have a much lower pathogenicity potential than clinical strains. Enterococci
      possess a competitive advantage over other microbiota in meat fermentations, and
      many enterococci isolated from sausages have the ability to produce enterocins
      harbouring antimicrobial activity against pathogens and spoilage microorganisms
      of meat concern. The application of enterocins producing enterococci or their
      purified metabolites, as extra hurdles for preservation in sausage fermentation
      and in sliced-vacuum packed cooked meat products can be beneficial, preventing
      the outgrowth of Listeria monocytogenes and slime-producing lactic acid bacteria.
      Enterocins and bacteriocinogenic enterococci hold considerable promise as
      alternatives to traditional chemical preservatives and they could be exploited
      for the control of emergent pathogens in meat products. Their inhibitory effect
      can be increased when used in conjunction with particular physical and chemical
      processes, but current regulation is hampering the application of purified
      bacteriocins.

PMID- 14596995
TI  - Enterococcus faecium RZS C5, an interesting bacteriocin producer to be used as a
      co-culture in food fermentation.
AB  - Enterocins, bacteriocins produced by enterococci, are gaining interest because of
      their industrial potential. Due to its bacteriocin production, Enterococcus
      faecium RZS C5, a natural cheese isolate, has a strong activity towards Listeria
      monocytogenes. For this reason, the strain may be applicable as a bacteriocin
      producing co-culture in food fermentation in order to reduce the risk on Listeria
      outgrowth. The strain displays remarkable bacteriocin production kinetics.
      Whereas most lactic acid bacteria produce bacteriocin in a growth-associated way
      until the beginning of the stationary phase, bacteriocin production by E. faecium
      RZS C5 in MRS broth at controlled pH values below 7.5 is characterised by a boost
      of bacteriocin activity levels in the very early growth phase. In addition,
      bacteriocin production kinetics are closely linked to the environmental and
      cultural conditions. However, no straightforward statement about the effect of
      environmental stress on bacteriocin production can be made since the effect is
      dependent on the type of stress applied. Kinetic experiments in milk and on pilot
      scale, applying Cheddar cheese-making conditions, have indicated that the strain
      may be effective as a bacteriocin-producing co-culture. Further research is
      needed to evaluate the use of E. faecium RZS C5 as a co-culture for the
      production of fermented sausage.

PMID- 14596997
TI  - EU assessment of enterococci as feed additives.
AB  - Particular micro-organisms such as enterococcal strains are used as probiotics in
      feed. Observations indicate a positive effect of such strains on the gut flora,
      especially for young animals or during feed transition phases. This favourable
      effect is perceived by the farmers as a means of maintenance of the health status
      of the animals (e.g. less diarrhoea) and results in significant improvement of
      animal performance. Micro-organisms have been used since the end of the 1980s in
      animal feeds and were strictly regulated in 1993, when they were introduced under
      the scope of Council Directive 70/524/EEC of 23 November 1970 on additives in
      animal nutrition on feed additives. After a transition period, which ended in the
      year 2000, every microbial strain must now be assessed by the EU bodies and
      authorised by a Commission Regulation, before it can be placed on the market for
      use in feedingstuffs. Council Directive 70/524/EEC on feed additives is based on
      three main principles: (1) pre-market authorisation, (2) positive list principle,
      and (3) thorough risk assessment of the effect of a particular strain on human
      and animal health as well as on the environment. Therefore, before introducing a
      new enterococcal strain preparation or promote a new use of an approved product,
      a dossier has to be submitted to the authorities, following the guidelines, as
      published in Commission Directive 94/40/EEC [Commission Directive 94/40/EC of 22
      July 1994 amending Council Directive 87/153/EEC fixing guidelines for the
      assessment of additives in animal nutrition]. These guidelines contain detailed
      evaluation methods. The safety requirements refer to (1) the target animal
      categories, (2) the consumer and the environment (presence of toxins and
      virulence factors as well as antibiotic resistance and transferability are
      assessed), and (3) the workers, based on requirements of Council Directive
      89/391/EEC.

PMID- 14596996
TI  - Homemade traditional cheeses for the isolation of probiotic Enterococcus faecium
      strains.
AB  - One hundred twenty-two strains of Enterococcus faecium isolated from Tafi Cheese,
      a homemade traditional cheese of the highlands in the province of Tucuman,
      Argentina, were evaluated for their potential application as starter cultures in
      the manufacture of this traditional cheese. Eleven of the 122 strains showing
      limited delays in growth in oxgall were selected for the study of bile salts
      hydrolase activity (BSH), cholesterol reduction, antimicrobial activity, and
      virulence determinants. Nine strains were able to remove cholesterol in in vitro
      assays, a property that was closely related to the bile salt hydrolase activity.
      Only two strains produced active bacteriocins against Listeria strains although
      genetic evidence for the bacteriocin structural gene was found in six other
      enterococci strains. No virulence factors were detected in any of the 11 selected
      strains of enterococci.

PMID- 14596998
TI  - Safety aspects of enterococci from the medical point of view.
AB  - Enterococci occur in a remarkable array of environments. They can be found in
      soil, food, and water, and make up a significant portion of the normal gut flora
      of humans (10(5)-10(7)/g of stool) and animals. As other bacteria of the gut
      flora, enterococci can also cause infectious diseases. Most clinical isolates are
      Enterocococus faecalis, which account for 80-90% of clinical strains.
      Enterocococus faecium accounts for 5-10% of such isolates. Typical enterococcal
      infections occur in hospitalised patients with underlying conditions representing
      a wide spectrum of severity of illness and immune modulation. Enterococci today
      rank second to third in frequency among bacteria isolated from hospitalised
      patients. They are isolated from urinary tract infections, intra-abdominal and
      pelvic infections, bacteremias, wound and tissue infections, and endocarditis-
      often as part of a polymicrobial flora. Surprisingly, little is known about the
      factors that contribute to the ability of enterococci to cause infections. Many
      strains of E. faecalis produce a cytolysin (haemolysin) exhibiting tissue
      damaging capacity. Further extracellular products often observed in clinical
      isolates are a proteinase (gelatinase), hyaluronidase, and extracellular
      superoxide. Furthermore, many of the clinical isolates possess the aggregation
      substance on the surface and an extracellular surface protein, both contributing
      to the adherence to eucaryotic cells. Some strains of E. faecalis, and many E.
      faecium strains are resistant to multiple antimicrobials. The ultimate role of
      all these factors in enterococcal pathogenicity remains to be determined. It was
      previously thought that enterococcal infections were endogenously acquired from
      the patient's own gut flora. A rather new concept that has emerged is that
      enterococcal disease is a two-stage process. There is an initial colonisation of
      the gastrointestinal tract by enterococcal strains possessing virulence traits
      and/or antibiotic resistance. Subsequently, this population spreads, often
      facilitated by antibiotic elimination of competitors. For a selected number of
      patients, there is subsequent tissue invasion from the gastrointestinal tract
      reservoir. From this concept, it can be deduced that enterococcal strains without
      virulence traits and antibiotic resistances exogenously transferred into the
      human gut via food products or probiotics will not represent any risk for
      immunocompetent individuals. In very severely immunocompromised patients,
      however, a risk for enterococcal disease by such strains cannot completely be
      excluded.

PMID- 14596999
TI  - Opsonophagocytic assay as a potentially useful tool for assessing safety of
      enterococcal preparations.
AB  - Enterococci are commonly used in foods and food additives. A number of putative
      virulence factors are usually evaluated to assure that the strains used are not
      harmful. We propose an additional test to assess the safety of these bacteria by
      testing the susceptibility to opsonophagocytic killing. One probiotic
      Enterococcus faecalis strain was compared to a collection of 27 clinical isolates
      and our results indicate that 89% of the clinical strains were less susceptible
      to killing mediated by normal rabbit sera. Opsonophagocytic killing is the best
      in vitro surrogate for a protective immune response against bacteria, and the
      susceptibility of bacteria against normal rabbit sera indicates that these
      strains may not be able to survive in the bloodstream of the host. Further
      studies comparing a larger collection of pathogenic strains with commensal
      isolates are necessary to confirm these findings.

PMID- 14597000
TI  - Occurrence and spread of antibiotic resistances in Enterococcus faecium.
AB  - Enterococci are the second to third most important bacterial genus in hospital
      infections. Especially Enterococcus (E.) faecium possesses a broad spectrum of
      natural and acquired antibiotic resistances which are presented in detail in this
      paper. From medical point of view, the transferable resistances to glycopeptides
      (e.g., vancomycin, VAN, or teicoplanin, TPL) and streptogramins (e.g.,
      quinupristin/dalfopristin, Q/D) in enterococci are of special interest. The VanA
      type of enterococcal glycopeptide resistance is the most important one (VAN-r,
      TPL-r); its main reservoir is E. faecium. Glycopeptide-resistant E. faecium
      (GREF) can be found in hospitals and outside of them, namely in European
      commercial animal husbandry in which the glycopeptide avoparcin (AVO) was used as
      growth promoter in the past. There are identical types of the vanA gene clusters
      in enterococci from different ecological origins (faecal samples of animals,
      animal feed, patients in hospitals, persons in the community, waste water
      samples). Obviously, across the food chain (by GREF-contaminated meat products),
      these multiple-resistant bacteria or their vanA gene clusters can reach humans.
      In hospital infections, widespread epidemic-virulent E. faecium isolates of the
      same clone with or without glycopeptide resistance can occur; these strains often
      harbour different plasmids and the esp gene. This indicates that hospital-adapted
      epidemic-virulent E. faecium strains have picked up the vanA gene cluster after
      they were already widely spread. The streptogramin virginiamycin was also used as
      feed additive in commercial animal husbandry in Europe for more than 20 years,
      and it created reservoirs for streptogramin-resistant E. faecium (SREF). In
      1998/1999, SREF could be isolated in Germany from waste water of sewage treatment
      plants, from faecal samples and meat products of animals that were fed
      virginiamycin (cross resistance to Q/D), from stools of humans in the community,
      and from clinical samples. These isolations of SREF occurred in a time before the
      streptogramin combination Q/D was introduced for therapeutic purposes in German
      hospitals in May 2000, while other streptogramins were not used in German
      clinics. This seems to indicate that the origin of these SREF or their
      streptogramin resistance gene(s) originated from other sources outside the
      hospitals, probably from commercial animal husbandry. In order to prevent the
      dissemination of multiple antibiotic-resistant enterococci or their transferable
      resistance genes, a prudent use of antibiotics is necessary in human and
      veterinary medicine, and in animal husbandry.

PMID- 14597001
TI  - Comparison of the incidence of virulence determinants and antibiotic resistance
      between Enterococcus faecium strains of dairy, animal and clinical origin.
AB  - Enterococci are part of the dominant microbiota of several dairy products. They
      are also present in the gut of humans and animals. Their presence in traditional
      raw milk cheeses is probably due to faecal contamination of milk during milking.
      Due to their importance as a cause of nosocomial infections, enterococci are
      acquiring increased significance. Such infections are becoming more and more
      difficult to treat as resistance to antibiotics increases. The aim of this
      investigation was to compare the potential virulence of Enterococcus faecium
      isolated from different ecological habitats and to establish if strains isolated
      from dairy products should really be considered as potential pathogens. In the
      present work, the antibiotic resistance pattern of 40 E. faecium strains isolated
      from dairy products, 26 E. faecium isolated from ewes' faeces and 28 clinical
      isolates of the same species was studied, and checks were made to see if known
      virulence determinants were present. Resistance to 12 different antibiotics
      commonly used in the treatment of human infections was tested using the broth
      microdilution method as described by the NCCLS. In addition, polymerase chain
      reaction (PCR) tests were carried out to see if genes for vancomycin resistance
      were present. The presence of the aggregation substance (AS) gene, the surface
      protein gene esp, the accessory colonisation factor ace, the Enterococcus
      faecalis endocarditis antigen efaA and the gelatinase gelE gene, which are
      involved in the virulence of enterococci, were also tested by PCR. The results of
      this study clearly indicate that E. faecium strains isolated from both cheese and
      sheep faeces are less pathogenic than those isolated from clinical samples. A
      similar pattern of resistance to antibiotics was observed in both dairy and
      animal strains. It was also found that there was difference in the kind of
      virulence determinants present in dairy and clinical isolates, while no virulence
      traits were found in sheep faeces strains. The results of this study suggest that
      E. faecium from traditional Sardinian raw milk cheeses should not be considered
      to be the main source of untreatable nosocomial enterococcal infections in humans
      in the island of Sardinia.

PMID- 14597002
TI  - Species identification and detection of vancomycin resistance genes in
      enterococci of animal origin by multiplex PCR.
AB  - A multiplex PCR assay for the differentiation of species and detection of
      vancomycin (van) resistance genes in enterococci was established. Three hundred
      sixty-seven enterococcal strains isolated from food were selected from a sample
      collection and were examined with regards to the existence of four vancomycin
      resistance genes (vanA, vanB, vanC1 and vanC2) and to species differentiation (E.
      faecalis, E. faecium, E. casseliflavus and E. gallinarum) by multiplex PCR. Apart
      from unambiguous results for the majority of strains, the E. faecium specific
      primers used here, showed weak points in the specificity and sensitivity,
      respectively. Despite these rare instances, we succeeded in optimising the
      multiplex PCR assay by variation of annealing temperature and primer combination.
      The assay presented here, with its optimised parameters, is therefore suitable
      for routine use and because of time and material saving, it is an alternative and
      rapid method in comparison to conventional tests.

PMID- 14597003
TI  - Species distribution and antibiotic resistance patterns of enterococci isolated
      from food of animal origin in Germany.
AB  - Presently, enterococci take the third place of bacterial pathogens associated
      with nosocomial infections, after staphylococci and Escherichia coli. Especially,
      the resistances of enterococci to several available antibiotics are threatening.
      We attempted to determine which species of enterococci could be found in food of
      animal origin and their significance according to their antibiotic resistances
      for human beings. From November 2000 to May 2002 we investigated 155 samples of
      food of animal origin bought in retail outlets in Germany: 27 samples of
      sausages, 19 of ham, 83 of minced meat, 26 of cheese. From these food samples we
      isolated 416 enterococcal strains. The most frequent species was Enterococcus
      faecalis (299 strains); furthermore, we found Enterococcus faecium (54 strains),
      Enterococcus durans together with Enterococcus hirae (24 strains), Enterococcus
      casseliflavus (22 strains), Enterococcus avium (9 strains) and Enterococcus
      gallinarum (8 strains). We focused on the resistance patterns of 118 selected E.
      faecium and E. faecalis strains to 13 antimicrobial active agents (ampicillin,
      amoxicillin/clavulanic acid, avilamycin, chloramphenicol, enrofloxacin,
      erythromycin, flavomycin, gentamicin, penicillin, quinupristin/dalfopristin,
      teicoplanin, tetracycline and vancomycin). From the clinical point of view, the
      situation of antibiotic resistance to the examined antimicrobial agents seemed to
      be favourable. The investigated strains were sensitive to ampicillin and
      amoxicillin/clavulanic acid. These antibiotics are, in combination with an
      aminoglycoside, for example gentamicin, agents of choice for the treatment of
      enterococcal infections in human medicine. Only one E. faecium strain was
      resistant to penicillin, while all strains were sensitive to the glycopeptide
      antibiotics, vancomycin and teicoplanin. Resistances found against the
      antibiotics, tetracycline, quinupristin/dalfopristin and erythromycin, are causes
      for concern.

PMID- 14597004
TI  - Gene transfer of vancomycin and tetracycline resistances among Enterococcus
      faecalis during cheese and sausage fermentations.
AB  - This study assessed the frequency of transfer of two mobile genetic elements
      coding for virulence determinants and antibiotic resistance factors, into food
      associated enterococci during fermentation processes. First, the transfer of the
      pheromone-inducible pCF10 plasmid, carrying tetracycline resistance and
      aggregation substance (AS) as virulence factor, between clinical and food strains
      of Enterococcus faecalis, was investigated in models of cheese and fermented
      sausage. The experiments demonstrated that even in the absence of selective
      tetracycline pressure, plasmid pCF10 was transferred from E. faecalis OG1rf cells
      to food strain E. faecalis BF3098c and that the plasmid subsequently persisted in
      these environments. Very high frequency of transfer was observed in sausage (10(
      3)/recipient) if compared to cheese (10(-6)) and plate mating (10(-4)).
      Transconjugants were subsequently verified by PCR. The second transmissible
      element was the plasmid harbouring the vancomycin resistance (VanA phenotype)
      from E. faecalis A256. The transfer of this antibiotic resistance to a food
      strain of E. faecalis was studied in vitro and in food models. Although the
      transfer of vancomycin resistance was achieved in all the environments, the
      highest conjugation frequencies were observed during the ripening of fermented
      sausages, reaching 10(-3) transconjugants/recipient cell. PCR confirmed the
      transfer of the VanA genotype into a food associated Enterococcus strain. This
      study showed that even in the absence of selective pressure, mobile genetic
      elements carrying antibiotic resistance and virulence determinants can be
      transferred at high frequency to food associated enterococci during cheese and
      sausage fermentation.

PMID- 14597005
TI  - Molecular structure and evolution of the conjugative multiresistance plasmid
      pRE25 of Enterococcus faecalis isolated from a raw-fermented sausage.
AB  - Plasmid pRE25 from Enterococcus faecalis transfers resistances against kanamycin,
      neomycin, streptomycin, clindamycin, lincomycin, azithromycin, clarithromycin,
      erythromycin, roxithromycin, tylosin, chloramphenicol, and nourseothricin sulfate
      by conjugation in vitro to E. faecalis JH2-2, Lactococcus lactis Bu2, and
      Listeria innocua L19. Its nucleotide sequence of 50237 base pairs represents the
      largest, fully sequenced conjugative multiresistance plasmid of enterococci
      (Plasmid 46 (2001) 170). The gene for chloramphenicol resistance (cat) was
      identified as an acetyltransferase identical to the one of plasmid pIP501 of
      Streptococcus agalactiae. Erythromycin resistance is due to a 23S ribosomal RNA
      methyl transferase, again as found in pIP501 (ermB). The aminoglycoside
      resistance genes are packed in tandem as in transposon Tn5405 of Staphylococcus
      aureus: an aminoglycoside 6-adenyltransferase, a streptothricin acetyl
      transferase, and an aminoglycoside phosphotransferase.). Identical resistance
      genes are known from pathogens like Streptococcus pyogenes, S. agalactiae, S.
      aureus, Campylobacter coli, Clostridium perfringens, and Clostridium difficile.
      pRE25 is composed of a 30.5-kbp segment almost identical to pIP501. Of the 15
      genes involved in conjugative transfer, 10 codes for putative transmembrane
      proteins (e.g. trsB, traC, trsF, trsJ, and trsL). The enterococcal part is joined
      into the pIP501 part by insertion elements IS1216V of E. faecium Tn1545 (three
      copies), and homologs of IS1062 (E. faecalis) and IS1485 (E. faecium). pRE25
      demonstrates that enterococci from fermented food do participate in the molecular
      communication between Gram-positive and Gram-negative bacteria of the human and
      animal microflora.

PMID- 14597006
TI  - Fusion protein system designed to provide color to aid in the expression and
      purification of proteins in Escherichia coli.
AB  - We have designed and constructed a new fusion expression vector (pKW32), which
      contains the His-tagged Vitreoscilla hemoglobin (VHb) coding gene upstream of the
      multiple cloning site. The pKW32 vector was designed to express target proteins
      as VHb fusions, which can be purified in one step by affinity chromatography. Due
      to the color of the heme in VHb, the VHb-fused target proteins have a red color
      that provides a visual aid for estimating their expression level and solubility.
      The red color can also be used as a visual marker throughout purification, while
      the concentration of the fusion protein can be determined by measuring the amount
      of VHb using carbon monoxide difference spectra. In addition, because of
      inherently high solubility of VHb, the fusion can increase the solubility of
      sparingly soluble target proteins. Target proteins can be easily separated from
      His-tagged VHb due to the presence of a thrombin-cleavage site between them. A
      mutant VHb, the soluble domain of Vitreoscilla cytochrome bo subunit II, and HIV
      integrase expressed and purified using the pKW32 system have native function. In
      addition, the integrase, which is known to be difficult to purify because of low
      solubility, was purified simply and without solubilizing agents using our system.

PMID- 14597007
TI  - Structural and functional analysis of pt38, a 2.9kb plasmid of Streptococcus
      thermophilus yogurt strain.
AB  - The cryptic plasmid pt38 (2911 bp) of Streptococcus thermophilus ST2783, a strain
      isolated from Bulgarian yogurt, was subcloned and sequenced. Five ORFs (ORF1 to
      ORF5) were identified, although putative transcription initiation and termination
      signals, and Shine-Dalgarno sequence could only be localized for three of them
      (ORF1, ORF2, and ORF5). ORF2 would specify a 142-amino acid protein sharing a
      high degree of homology with plasmid-born low-molecular-weight heat stress
      proteins described in a variety of S. thermophilus strains. On the other hand,
      ORF1 would encode a 311-residue protein, which was found to be almost identical
      to the putative Rep proteins of previously sequenced S. thermophilus rolling
      circle-replicating plasmids. Intracellular single-stranded pt38 DNA was detected,
      showing that, in fact, the plasmid replicates via a rolling circle mechanism. A
      putative double-strand origin with significant homology to that of pC194, and a
      ssoA-type single-strand origin were also identified on the nucleotide sequence of
      pt38. A DNA region that can be transcribed into a small RNA (ctRNA) complementary
      to the leader segment of the rep (ORF1) mRNA is proposed to be involved in the
      control of plasmid replication. In vitro synthesis of this ctRNA was observed,
      and this constitutes the first report on the existence of such antisense RNAs,
      likely acting as regulatory elements, in S. thermophilus plasmids.

PMID- 14597008
TI  - Sequence and genetic organization of the 19.3-kb erythromycin- and dalfopristin
      resistance plasmid pLME300 from Lactobacillus fermentum ROT1.
AB  - Lactobacillus fermentum ROT1 was isolated from a raw milk dairy product. It is
      resistant to novobiocin, tetracycline, erythromycin and dalfopristin. A
      chromosomal tetracycline-resistance determinant was identified as tetM. A 19,398
      bp plasmid (pLME300), present in several erythromycin-resistant strains of Lb.
      fermentum, was isolated from strain ROT1 and completely sequenced. Based on
      putative open reading frames, pLME300 contains at least four different functional
      regions. In region I, ORF1 shows high homologies to replication proteins of
      different theta-replicating plasmids. In addition, a tandem repeat of a 22-bp
      sequence appears 4.5 times. In region II, ORF3 may code for a methylase, and ORF4
      has homologies to Mrr restriction system proteins of Deinococcus radiodurans and
      Escherichia coli suggesting a restriction-modification system. Region III
      harbours antibiotic-resistance genes, coding for a macrolide-lincosamide
      streptogramin B (MLS) methylase Erm(LF) and the streptogramin A acetyltransferase
      Vat(E), which is identical to Vat(E) from Enterococcus faecium. Furthermore,
      region III shows a 91% nucleotide sequence identity to an erm-vat linkage of E.
      faecium. Region IV carries ORFs that appear to be involved in plasmid
      mobilization as characterized by a putative origin of transfer and a mobilization
      protein. pLME300 is the largest completely sequenced multi-resistance plasmid
      isolated from any Lactobacillus strain so far.

PMID- 14597009
TI  - Type I restriction enzyme with RecA protein promotes illegitimate recombination.
AB  - Illegitimate (non-homologous) recombination requires little or no sequence
      homology between recombining DNAs and has been regarded as being a process
      distinct from homologous recombination, which requires a long stretch of homology
      between recombining DNAs. However, we have found a type of illegitimate
      recombination that requires an interaction between long homologous DNA sequences.
      It was detected when a plasmid that carried 2-kb-long inverted repeats was
      subjected to type I (EcoKI) restriction in vivo within a special mutant strain of
      Escherichia coli. In the present work, we analyzed genetic requirements for this
      type of illegitimate recombination in well-defined genetic backgrounds. Our
      analysis demonstrated dependence on RecA function and on the presence of two
      EcoKI sites on the substrate DNA. These results are in harmony with a model in
      which EcoKI restriction enzyme attacks an intermediate of homologous
      recombination to divert it to illegitimate recombination.

PMID- 14597010
TI  - Peripheral sequences of the Serratia entomophila pADAP virulence-associated
      region.
AB  - Some strains of the Enterobacteriaceae Serratia entomophila and Serratia
      proteamaculans cause amber disease in the grass grub, Costelytra zealandica
      (Coleoptera: Scarabaeidae), an important pasture pest in New Zealand. The genes
      responsible for this disease reside on a large, 155-kb plasmid designated amber
      disease-associated plasmid (pADAP). Herein, we report the DNA sequencing of
      approximately 50 kb upstream and 10 kb downstream of the virulence-encoding
      region. Based on similarity with proteins in the current databases, and potential
      ribosome-binding sites, 63 potential ORFs were determined. Eleven of these ORFs
      belong to a type IV pilus cluster (pilL-V) and a further eight have similarities
      to the translated products of the plasmid transfer traH-N genes of the plasmid
      R64. In addition, a degenerate 785-nt direct repeat flanks a 44.7-kb region with
      the potential to encode three Bacillus subtilis Yee-type proteins, a fimbrial
      gene cluster, the sep virulence-associated genes and several remnant IS elements.

PMID- 14597011
TI  - Production of functional recombinant tyrosine hydroxylase by the BPV-1 expression
      plasmids in the cell cultures.
AB  - Bovine papilloma virus type-1 (BPV-1)-based expression plasmids TkBPVTH and
      CGalBPVTH encoding the rat tyrosine hydroxylase (TH) enzyme have been designed
      for the development of gene therapy for experimental Parkinson's disease. The aim
      of the present work was to examine the transfection of BPVTH plasmids to express
      a dopaminergic transgene in the monkey CV1-P fibroblast, rat C6 glioma and human
      NHA astrocyte cell cultures. The biological function of the transgene was
      estimated by analyzing the production of recombinant TH mRNA and protein, and the
      synthesis of L-dopa and dopamine. The highest transfection efficiency was
      obtained using TkBPVTH plasmids (5 microg). Furthermore, the expression of
      TkBPVTH plasmids was associated with significant synthesis of TH enzyme and L
      dopa in the C6 and NHA cell cultures.

PMID- 14597012
TI  - pHP489, a Helicobacter pylori small cryptic plasmid, harbors a novel gene coding
      for a replication initiation protein.
AB  - We have analyzed a Helicobacter pylori plasmid, pHP489. The 1222-bp nucleotide
      sequence had one open reading frame, a DnaA-binding site, one direct repeat, and
      three inverted repeats. The (G+C) content of pHP489 was 33.3%. Although the
      nucleic acid sequence and deduced amino acid sequence were homologous to those of
      other bacterial plasmid Rep proteins, the degree of similarity was very low. A
      deletion analysis showed that the Rep protein was not required for the
      replication of pHP489 in its H. pylori host, but the host replication machinery
      was needed.

PMID- 14597013
TI  - Direct repeat sequences are essential for function of the cis-acting locus of
      transfer (clt) of Streptomyces phaeochromogenes plasmid pJV1.
AB  - The functionality of direct and inverted repeat sequences inside the cis acting
      locus of transfer (clt) of the Streptomyces plasmid pJV1 was determined by
      testing the effect of different deletions on plasmid transfer. The results show
      that the single most important element for pJV1 clt function is a series of
      evenly spaced 9 bp long direct repeats which match the consensus
      CCGCACA(C/G)(C/G), since their deletion caused a dramatic reduction in plasmid
      transfer. The presence of these repeats in the absence of any other clt sequences
      allowed plasmid transfer to occur at a frequency that was at least two orders of
      magnitude higher than that obtained in the complete absence of clt. A database
      search revealed regions with a similar organization, and in the same position, in
      Streptomyces plasmids pSN22 and pSLS, which have transfer proteins homologous to
      those of pJV1.

PMID- 14597014
TI  - The editor's workshop. Ben Franklin's hometown rings the Liberty Bell for Naspag.

PMID- 14597015
TI  - Common pediatric and adolescent skin conditions.
AB  - Skin lesions are encountered in all areas of medicine, and it is therefore
      important for physicians to understand the fundamentals of explaining and
      diagnosing common skin conditions. This article begins with a discussion of
      description and documentation of skin lesions based on color, size, morphology,
      and distribution. Pigmentation disorders such as vitiligo are depicted. Cutaneous
      growths that are found in the pediatric and adolescent population include
      acrochordons, dermatofibromas, keloids, milia, neurofibromas, and pyogenic
      granulomas. Treatment of these growths usually involves observation or curettage
      with electrodessication.Psoriasis, atopic dermatitis, poison ivy, and eczema are
      comprised of scaling patches and plaques; poison ivy and atopic dermatitis may
      also present with bullous and vesicular changes. Therapy typically consists of
      topical emollients and corticosteroids; phototherapy is reserved for refractory
      cases. Acne vulgaris is the most common skin disease of the pediatric and
      adolescent population. This condition can be psychologically debilitating and,
      therefore, proper treatment is of paramount importance. Therapeutic options
      include topical as well as oral antibiotics and retinoids. Extreme caution must
      be used when prescribing retinoids to post-pubescent females, as these agents are
      teratogenic. Vascular anomalies are most commonly exemplified as port wine stains
      and hemangiomas. Port wine stains may be treated with pulsed dye laser or may be
      observed if they are not of concern to the patient or physician. Hemangiomas
      typically spontaneously regress by age ten; however, there has been recent
      concern that certain cases may need to be treated. Dermal rashes may be localized
      or generalized. Treatment of generalized drug eruptions involves elimination of
      the inciting agent, topical antipruritics, and systemic corticosteroids for
      severe reactions. Infectious etiologic agents of skin disease include bacteria,
      fungi, and viruses. Many sexually transmitted diseases are bacterial or viral in
      origin and present as a rash or ulcer. Impetigo is a bacterial infection which
      may present as a bullous eruption or as an erosion with a honey colored crust.
      Other bacterial infections include erythema chronicum migrans, folliculitis, and
      cellulitis. Fungal infections include the various forms of tinea and are usually
      treated with topical antifungals; if the infection is located in a hair-bearing
      area, systemic antifungals are necessary. Viral infections include warts,
      varicella, molluscum contagiosum, and herpes. Treatment varies from observation
      or antivirals for varicella to cryosurgery and topical imiquimod for warts.
      Finally, scabies and lice are infectious agents that can be treated with
      permethrin and pyrethrin solutions.

PMID- 14597016
TI  - Vaginal calculus as a late complication of bladder exstrophy.
AB  - STUDY OBJECTIVE: To document an unusual finding of a vaginal calculus in a
      patient with bladder exstrophy. DESIGN: Case report. SETTING: Tertiary Centre,
      Royal Children's Hospital, Melbourne, Australia. PARTICIPANTS: Fourteen year old
      female. INTERVENTIONS: Cystotomy, introitoplasty. MAIN OUTCOME: Removal of
      vaginal calculus. MEASURES: None. RESULTS: Documentation and removal of a vaginal
      calculus. CONCLUSIONS: Vaginal calculi should be included in the differential
      diagnosis of urolithiasis in patients with bladder exstrophy.

PMID- 14597017
TI  - The long term outcome of feminizing genital surgery for congenital adrenal
      hyperplasia: anatomical, functional and cosmetic outcomes, psychosexual
      development, and satisfaction in adult female patients.
AB  - BACKGROUND: There are only a few reports analyzing the long term outcome of
      feminizing surgery in females with congenital adrenal hyperplasia (CAH). Such
      analysis is crucial to evaluate the treatment and to make necessary adjustments.
      STUDY OBJECTIVES: To evaluate the adult outcome after feminizing surgery in adult
      females with salt wasting CAH. DESIGN: Retrospective observational followup
      investigation. SETTING: Outpatient clinic of a University Medical Center, in
      2002. PARTICIPANTS: Eight patients (born 1973-1983) who underwent feminizing
      surgery in infancy by the same procedure and the same pediatric surgeon in our
      center, and 19 healthy female controls (for visual analog scales). METHODS: (a)
      Study of patients' records (n=8); (b) Systematic evaluation of the current
      situation (n=6): uroflowmetry, a written questionnaire to screen for
      psychopathology (Youth Adult Self Report, YASR), structured gynecologic
      examination and a structured psychosexual interview, including scoring on visual
      analog scales. RESULTS: (a) The first surgery (age 0.1-3.7 yr) consisted of
      clitoris reduction and vaginoplasty (single-stage) in 7 patients and clitoris
      reduction only in one patient. The latter patient had vaginoplasty in puberty. In
      puberty, 6 of the 7 patients with an initial single-stage procedure required re
      vaginoplasty. All 6 patients who participated in this systematic evaluation had
      undergone (re-) vaginoplasty in puberty; (b) 2 of the 6 patients experienced some
      urinary incontinence, and in one of them, the uroflowmetry result was abnormal.
      The YASR showed no psychopathology, except for 1 patient with a slightly elevated
      externalizing score. Gynecologic examination (n=5) revealed vaginal strictures in
      3 patients (1 severe, 2 mild). The 2 patients without vaginal strictures had
      coitus regularly. In the interview, 2 patients called themselves bisexual, the
      other 4 heterosexual. None of the patients had homosexual contacts. Sexual
      developmental milestones (romantic interest, falling in love, kissing and
      petting, coitus) had been reached by all, except for 1 patient who did not have
      coitus yet. In the patient group, satisfaction with height, body hair, and
      external genitalia and sexual fantasies and interest, measured with visual analog
      scales, was not different compared to the control group, except for satisfaction
      with total body appearance, which was significantly lower in the patients.
      CONCLUSION: Despite the poor outcome of the initial single-stage surgery in
      infancy and the inevitable re-operation in puberty, the adult outcome in our
      study population seems more positive than the findings in the few previous
      reports, especially with respect to sexual development and activity.

PMID- 14597018
TI  - Adolescents' compliance with return visits for depot medroxyprogesterone
      initiation.
AB  - STUDY OBJECTIVES: To determine if and when female adolescents choosing depot
      medroxyprogesterone would return for a second visit for initiation of the method.
      DESIGN/SETTING: Retrospective chart review at an adolescent clinic in an urban
      health department in St. Louis, MO. PARTICIPANTS: Female adolescents aged 12-19
      years old, at the initial or annual family planning visit, who chose depot
      medroxyprogesterone (DMPA) as their contraceptive choice but were unable to get
      the initial injection on the day of the visit. MAIN OUTCOME MEASURE: Time to
      return visit. RESULTS: A total of 144 subjects were included in the analysis. 92%
      or 133 subjects returned for a second visit. The average time to return visit was
      over 3 months, or 104 days (range 1-650 days). Teens who returned in less than 1
      month were more likely to receive a hormonal contraceptive method. Only 68% of
      all returning teens received DMPA while 7% became pregnant prior to their return.
      CONCLUSION: Protocols requiring a second visit for initiation of DMPA serve as a
      barrier to contraceptive care.

PMID- 14597019
TI  - Myometrial hyperplasia in pediatric, adolescent, and young adult uteri.
AB  - OBJECTIVES: To evaluate if myometrial hyperplasia is a congenital variation in
      myometrial differentiation, or an acquired structural disorder of the myometrium,
      this study evaluated whether myometrial hyperplasia was present in uteri of
      children, adolescents, and young adults. METHODS: We studied 19 pediatric/young
      adult uteri in cases with no clinical history of uterine disease. Random
      photomicrographs at 100x, taken at 1, 5, and 10 mm beneath the endometrium, were
      assessed for increased cellularity and nucleus/cell ratio, as compared to normal
      myometrium in the outer third of the same uterus. RESULTS: Myometrial hyperplasia
      was generally absent in prepubertal uteri, first appeared in adolescent uteri
      just beneath the endometrium, and was found at 5 mm depth only after age 18. It
      decreased with depth beneath the endometrium (P<0.05). CONCLUSIONS: Myometrial
      hyperplasia is not a congenital anatomic variation in myometrial differentiation,
      but rather an age-related acquired structural variation. Its relationship to
      common adolescent symptoms of dysmenorrhea and anovulatory bleeding remains
      unknown and unexplored.

PMID- 14597020
TI  - Presenting and long-term clinical implications and fecundity in females with
      obstructing vaginal malformations.
AB  - OBJECTIVE: To evaluate presenting and long-term clinical consequences in females
      with obstructing vaginal anomalies. DESIGN: A retrospective study. SETTING: A
      university hospital in southern Finland. PARTICIPANTS: Twenty-six females with
      obstructing vaginal malformations. The conditions were classified into transverse
      vaginal obstruction (transverse septum or imperforate hymen) and longitudinal
      vaginal obstruction (longitudinal vaginal septum). INTERVENTIOS: 13 out of 16
      women with transverse vaginal obstruction underwent incision of the imperforate
      hymen and three underwent excision of a complete transverse vaginal septum. Ten
      patients with obstructing hemivagina had incision of the longitudinal vaginal
      septum. MAIN OUTCOME MEASURES: Presenting symptoms and delay in diagnosis,
      outcome of primary surgical treatment, possible late complaints associated with
      obstruction, fecundity, perinatal outcome, and presence of other anomalies were
      studied. The mean followup period in the transverse and longitudinal obstruction
      group respectively was 13 years (range 1-29) and 16 years (range 1-44). RESULTS:
      Transverse vaginal obstructions were diagnosed within less than a month from the
      primary symptoms, while the diagnosis of longitudinal obstruction was delayed for
      an average of 27 months. Two out of three females with transverse vaginal septum
      underwent re-operation for vaginal constriction and three out of 10 with
      longitudinal vaginal septum had re-excision of the septum. All females with
      longitudinal obstruction had uterine and renal malformations as opposed to those
      with transverse vaginal obstruction. In the transverse vaginal obstruction group,
      two out of the six females who had their renal status assessed had double
      ureters. Dysfunctional uterine bleeding (19% in the transverse and 40% in the
      longitudinal obstruction group), dyspareunia (30% and 0%) and dysmenorrhea (19%
      and 20%) were the most common complaints during the followup. No endometriosis
      was found in the group that underwent a subsequent laparotomy or laparoscopy
      (18/26). Female infertility was not found in those 14 females who were attempting
      to conceive. Twenty-five (89%) out of 28 pregnancies ended in delivery, the live
      birth rate being 82% in the longitudinal and 94% in the transverse obstruction
      group. CONCLUSION: Accurate diagnosis together with adequate treatment may reduce
      the need for re-operations in cases with obstructing vaginal malformations. No
      specific gynecologic long-term clinical symptoms were identified in obstructing
      vaginal anomalies.

PMID- 14597021
TI  - The impact of using emergency contraception on reproductive health outcomes: a
      retrospective review in an urban adolescent clinic.
AB  - The effort to make emergency contraception (EC) more easily available has been
      challenged by concerns that prescribing EC may tempt adolescents to have
      unprotected intercourse, resulting in higher rates of pregnancy and sexually
      transmitted infections (STIs). This study examined differences in reproductive
      health history and outcomes among girls who were prescribed EC compared with
      those seeking other reproductive health care. In a retrospective chart review,
      the subjects (182 total: 92 EC, 90 control) were girls aged 13 to 21 years, 63%
      black and 31% white, in an urban, hospital-based adolescent outpatient clinic.
      Pregnancies, STIs, and visits for first pelvic examination and Pap smear were
      compared for the 12 months before the identifying visit (IDV) and for up to 2
      years after the IDV (mean: 10.9 months+/-8.2 months). Twenty-six subjects became
      pregnant with no significant difference between groups. Control subjects were
      found to have a higher incidence of chlamydia. Before the IDV, EC users were more
      likely than controls to have never had a pelvic examination (23% vs. 6%, P<0.002)
      or a Pap smear (24% vs. 6%, P<0.002). However, 80% of EC subjects who had never
      had a pelvic examination received one as a result of the initial visit and follow
      up related to receiving EC. Using EC is not associated with increased risk for
      future STIs and pregnancy among adolescent girls. Requesting EC may initiate
      routine gynecologic care.

PMID- 14597023
TI  - Management quandary. Vulvar trauma in a young girl.

PMID- 14597022
TI  - Association between vegetarian diet and menstrual problems in young women: a case
      presentation and brief review.
AB  - In the last twenty years, several studies have suggested the existence of an
      association between vegan diets and adolescent menstrual disorders. We share our
      experience with this problem and a review of the literature on the subject. We
      conclude that despite the existence of some evidence to the possible association
      between vegetarian diet and menstrual disorders, it is still not clear if this
      association is due solely to the vegetarian diet or due to the overall inadequate
      nutrition with decreased proportions of fat and protein in the diet. We believe
      that more prospective, well controlled studies are needed to truly explain this
      association.

PMID- 14597024
TI  - Approaching the adolescent patient from a psychodevelopmental framework.

PMID- 14597025
TI  - The depressed teen and contraception.

PMID- 14597028
TI  - Acute endophthalmitis following intravitreal triamcinolone acetonide injection.
AB  - PURPOSE: To report the clinical features, causative organisms, management, and
      visual acuity outcomes of eight eyes of eight patients who developed acute
      postoperative endophthalmitis following intravitreal injection of triamcinolone
      acetonide (IVTA). DESIGN: Retrospective, multicenter, interventional, case
      series. METHODS: A retrospective, interventional, case series of all patients
      with acute postoperative endophthalmitis following IVTA at seven academic
      clinical centers between March 2001 and July 2002. RESULTS: A total of 922 IVTAs
      were performed. Eight eyes of eight patients with acute postoperative
      endophthalmitis were identified in the 6 weeks following IVTA for an incidence of
      0.87% (95% confidence interval of 0.38% to 1.70%). The median time to
      presentation was 7.5 days (range, 1-15 days) after IVTA. The most common clinical
      findings were iritis (n = 8), vitritis (n = 8), hypopyon (n = 8), pain (n = 7),
      red eye (n = 6), and decreased vision (n = 5). The median presenting visual
      acuity was 20/1127 (range, 20/60 to light perception). Initial treatment
      consisted of vitreous tap and injection of antibiotics (n = 6) or pars plana
      vitrectomy and injection of intravitreal antibiotics (n = 2). Intraocular
      cultures yielded identification in seven patients. One demonstrated intracellular
      gram-positive cocci in chains with numerous polymorphonuclear cells on gram
      stain. The median postinfection vision was 20/400 (range, 20/40 to no light
      perception). Three patients ended up with no light perception visual acuity,
      including enucleation (n = 1) and phthisis (n = 1). CONCLUSIONS: Acute
      postoperative endophthalmitis following IVTA occurs rapidly and can result in
      severe loss of vision.

PMID- 14597029
TI  - Parents' expectations regarding their children's eye care: interview results.
AB  - PURPOSE: To determine a relevant set of concerns that parents express as
      expectations regarding their children's eye care. DESIGN: Qualitative, cross
      sectional, pilot study. METHODS: A total of 48 interviews were conducted with
      parents of pediatric ophthalmology patients at Duke University Eye Center and the
      McGovern Davidson Children's Health Center at Duke University to elicit parents'
      expectations regarding their children's eye care. Interviews were audiotaped,
      transcribed, and coded for parent expectations. RESULTS: Content analysis of
      transcripts from the 48 interviews yielded 35 different expectation areas for eye
      care, which were further classified into six groups: (1) Communication, (2)
      Interpersonal Manner, (3) Doctor's Skill, (4) Examination and Testing, (5)
      Logistics, and (6) Other. The six expectation areas most frequently identified by
      parents as the single "most important" expectation were the following: (1)
      Clinical Competence, (2) Interaction with Child, (3) Education/Training, (4)
      Explanation in Clear Language, (5) Information about Diagnosis, and (6) Personal
      Connection. CONCLUSIONS: Parents of pediatric ophthalmology patients expressed
      expectation areas in the Communication group more frequently than any other
      group. However, when asked to identify their single most important expectation
      area, more than half of parents identified Clinical Competence.

PMID- 14597030
TI  - Corneal thickness as a risk factor for visual field loss in patients with
      preperimetric glaucomatous optic neuropathy.
AB  - PURPOSE: To determine whether central corneal thickness (CCT) is a risk factor
      for visual field loss development among patients diagnosed with preperimetric
      glaucomatous optic neuropathy (GON). DESIGN: Observational cohort study. METHODS:
      The study included 98 eyes of 98 patients with GON, with a mean follow-up time of
      4.3 +/- 2.7 years. Diagnosis of GON was based on masked assessment of optic disk
      stereophotographs. All patients had normal standard automated perimetry visual
      fields at baseline. Criteria for visual field abnormality were derived from a
      prior study. Several clinical factors (CCT, intraocular pressure, vertical cup-to
      disk ratio, refraction, age, gender, family history of glaucoma, high blood
      pressure, cardiovascular disease, and migraine) were investigated to ascertain
      whether there is an association with development of repeatable visual field loss.
      Cox proportional hazards models were used to obtain hazard ratios (HR) and
      identify factors that predicted which individuals developed glaucomatous visual
      field loss during the follow-up period. RESULTS: Thirty-four patients (35%)
      developed repeatable visual field abnormality during follow-up. In multivariate
      analysis, risk factors that predicted the development of visual field loss were a
      thinner CCT (adjusted HR = 1.62/40 microm thinner; P =.023; 95% confidence
      interval [CI]: 1.07-2.45), higher baseline intraocular pressure (adjusted HR =
      1.07/mm Hg; P =.022; 95% CI: 1.01-1.14), and larger baseline vertical cup-to-disk
      ratio (adjusted HR = 1.63/0.1 larger; P =.009; 95% CI: 1.13-2.35). The mean +/-
      standard deviation CCT of GON patients who developed visual field loss was 543 +/
      36 microm compared with 565 +/- 35 microm of those who did not develop visual
      field abnormalities (P =.005, Student t test). CONCLUSIONS: Central corneal
      thickness is a risk factor for development of visual field loss among patients
      diagnosed with preperimetric GON. It is important to consider CCT when
      establishing target intraocular pressure of patients with GON.

PMID- 14597031
TI  - Radial optic neurotomy as treatment for central retinal vein occlusion.
AB  - PURPOSE: To review our initial experience with radial optic neurotomy as
      treatment for retinal vein occlusion. DESIGN: Interventional case series.
      METHODS:  PATIENT POPULATION: five patients (four with central retinal vein
      occlusion and one with hemiretinal vein occlusion). INTERVENTION: Pars plana
      vitrectomy with radial optic neurotomy was performed in each case. MAIN OUTCOME
      MEASURES: Best-corrected visual acuity, presence of macular edema, perfusion
      status, and time to venous phase of the angiogram were reviewed retrospectively.
      RESULTS: Mean preoperative visual acuity was 4/200. Preoperatively, the vein
      occlusion was perfused in one (20%), nonperfused in one (20%), and indeterminate
      in three (60%). Mean follow-up time was 4.5 months. Mean postoperative visual
      acuity was 20/400 at last follow-up. Four patients (80%) had improvement in
      visual acuity and one (20%) worsened. Two patients (40%) improved to 20/80
      postoperatively. In four cases (80%), disk congestion improved and intraretinal
      hemorrhage reabsorbed more quickly than would be expected without treatment. Time
      to the venous phase of fluorescein angiography improved slightly in three cases
      (60%) postoperatively. Perfusion status as determined by fluorescein angiography
      was not significantly altered postoperatively. One patient (20%) had resolution
      of macular edema postoperatively as shown by volumetric optical coherence
      tomography. One patient developed choroidovitreal neovascularization and one
      developed iris neovascularization postoperatively, both of which responded to
      panretinal photocoagulation. CONCLUSIONS: Radial optic neurotomy may improve
      visual acuity in eyes with central retinal vein occlusion, although
      choroidovitreal neovascularization from the neurotomy site can occur. Further
      study is needed to determine its role in the management of central vein
      occlusion.

PMID- 14597032
TI  - Factors that predict the benefit of lowering intraocular pressure in normal
      tension glaucoma.
AB  - PURPOSE: To study whether the benefit of lowering of intraocular pressure (IOP)
      varies according to certain traits. DESIGN: Randomized clinical trial, secondary
      analysis. METHODS: Visual field data were analyzed from 144 subjects (144 eyes)
      randomized not to receive IOP-lowering treatment or to have the IOP lowered by
      30%. Survival analyses were applied to compare times to progression between
      groups. Changes in mean deviation global index over time were compared with
      multilevel random effects models. RESULTS: By univariate analysis, the most
      readily demonstrated treatment benefit occurred in patients without baseline disk
      hemorrhage, of female gender, with family history of glaucoma, without family
      history of stroke, without personal history of cardiovascular disease, and with
      mild disk excavation; IOP lowering benefited females with migraine (P <.05) but
      perhaps without eliminating all migraine-associated risk. CONCLUSIONS: It is
      suggested that different factors may contribute to the glaucomatous optic
      neuropathy in different cases of normal tension glaucoma, interacting with IOP to
      different degrees and, thereby, affecting the magnitude of benefit of IOP
      lowering. Further study is required to establish interactions that would have
      implications for understanding the disease mechanisms in glaucomatous cupping,
      for guiding development of new treatment modalities, and for making clinical
      decisions regarding prognosis and management of individual patients.

PMID- 14597033
TI  - Macular translocation surgery with 360-degree peripheral retinectomy following
      ocular photodynamic therapy of choroidal neovascularization.
AB  - PURPOSE: To determine the visual outcomes of eyes that underwent macular
      translocation surgery with 360 degrees peripheral retinectomy and silicone oil
      tamponade (MTS360) following ocular photodynamic therapy (OPT) with verteporfin
      for subfoveal choroidal neovascularization (CNV) associated with age-related
      macular degeneration (ARMD). DESIGN: Observational case series. METHODS: A
      retrospective review of patients who underwent MTS360 with silicone oil tamponade
      from August 5, 1998 through December 1, 2002. Patients who had at least one
      episode of OPT with verteporfin before surgery were identified. The number of OPT
      session, best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual
      acuity, complications (including postoperative CNV, retinal detachment [RD]), the
      presence or absence of cystoid macular edema (CME) by optical coherence
      tomography (OCT) were recorded. RESULTS: Eight eyes of eight patients were
      identified that fulfilled the inclusion criteria. All eyes had at least one
      episode of OPT (mean, 1.5 treatments). All of these patients at the time of
      MTS360 demonstrated continued visual loss following the most recent OPT session.
      The mean preoperative visual acuity was 56 letters. Four of the eight eyes
      demonstrated CME by OCT on preoperative examination. There were no significant
      postoperative complications other than one eye that had a successful repair of an
      RD. At 3 months, the mean visual acuity was 54 letters. At last follow-up (mean,
      10 months), the mean visual acuity was 61 letters (P =.5). The final mean visual
      acuity change for the patients who had only one prior OPT (five eyes) was +10
      letters. The mean final visual acuity change for the patients who had multiple
      OPT sessions (three eyes) was -1 letter. Three of the four eyes that had
      preoperative CME continued to demonstrate CME at last follow-up. Two eyes that
      had concurrent cataract extraction surgery with MTS360 did not develop CME. No
      eyes developed a recurrent CNV during the postoperative period. CONCLUSIONS:
      MTS360 with silicone oil tamponade for CNV associated with ARMD appears to be a
      viable option for patients who are continuing to lose vision in their better
      seeing eye following OPT with verteporfin. MTS360 appears to be effective in
      stabilizing vision, especially in patients who had previously undergone only one
      OPT session. Further studies are indicated to evaluate the efficacy of MTS360 in
      this current era of OPT.

PMID- 14597034
TI  - Treatment of choroidal neovascularization in central serous chorioretinopathy by
      photodynamic therapy with verteporfin.
AB  - PURPOSE: To evaluate the safety and efficacy of photodynamic therapy (PDT) with
      verteporfin in the treatment of patients with choroidal neovascularization (CNV)
      secondary to central serous chorioretinopathy (CSC). DESIGN: Open-label, two
      center, noncomparative, prospective interventional case series. METHODS:
      Consecutive patients with subfoveal or juxtafoveal CNV secondary to CSC were
      recruited and treated with a standard regimen of PDT with verteporfin. At regular
      3-month follow-up examinations, re-treatment was considered if fluorescein
      angiography showed evidence of leakage. Outcome measures included the proportion
      of patients who had improvement (gained 2 more lines), stable, or loss (dropped
      in 2 or more lines) in vision at the final follow-up and the changes in best
      corrected visual acuity (BCVA) from baseline. RESULTS: Ten eyes of 10 patients
      were recruited into the study. The mean age of the patients was 57.3 years with a
      mean follow-up duration of 12.6 months. At the last follow-up, six (60%) eyes
      gained 2 or more lines of BCVA with four (40%) patients having final BCVA of
      within 1 line. No patient lost 2 or more lines of BCVA. The mean logarithm of the
      minimal angle of resolution BCVA improvement after PDT was 2.4 lines (Wilcoxon
      signed-rank test, P =.013). No patient suffered serious ocular or systemic
      complications from PDT. CONCLUSIONS: Photodynamic therapy with verteporfin
      therapy is a safe and well-tolerated treatment in patients with CNV associated
      with CSC. A randomized, controlled trial with a longer follow-up period is
      warranted to further study the efficacy of PDT in the management of CNV secondary
      to CSC.

PMID- 14597035
TI  - Positron emission tomography scanning in essential blepharospasm.
AB  - PURPOSE: To localize in the brain using positron emission tomography neuroimaging
      with (18)fluorodeoxyglucose [PET ((18)FDG)] differences in glucose metabolism
      between patients with essential blepharospasm (EB) and controls. DESIGN:
      Prospective case-control study. METHODS: Positron emission tomography
      neuroimaging with (18)fluorodeoxyglucose was performed in 11 patients with EB and
      11 controls matched for age and gender. Global analysis of images was used to
      localize differences in glucose metabolism between groups. RESULTS: Multiple
      cortical and subcortical abnormalities were observed in EB patients in comparison
      with controls. Cortical areas with the largest and most significant clusters of
      increased glucose uptake were the inferior frontal gyri, right posterior
      cingulate gyrus, left middle occipital gyrus, fusiform gyrus of the right
      temporal lobe, and left anterior cingulate gyrus. Cortical areas with the largest
      and most significant clusters of decreased glucose uptake were the inferior
      frontal gyri, ventral to the area of increased glucose metabolism. Subcortical
      abnormalities, consisting of increased glucose uptake, involved the right caudate
      and consisting of decreased glucose uptake, involved the left inferior cerebellar
      hemisphere and thalamus. CONCLUSIONS: Global analysis of positron emission
      tomography neuroimaging with (18)fluorodeoxyglucose neuroimaging in EB patients
      in comparison with controls demonstrates a pattern of abnormalities involving
      several cortical and subcortical areas that control blinking, including the
      inferior frontal lobe, caudate, thalamus, and cerebellum.

PMID- 14597036
TI  - The T-lymphocyte chemoattractant Mig is highly expressed in vernal
      keratoconjunctivitis.
AB  - PURPOSE: To examine the expression of the three interferon-gamma-inducible CXCR3
      binding chemokines, CXCL10/IP-10 (interferon-gamma-inducible protein of 10 KDa),
      CXCL9/Mig (monokine induced by interferon-gamma), and CXCL11/I-TAC (interferon
      inducible T-cell alpha chemoattractant) in the conjunctiva of patients with
      vernal keratoconjunctivitis (VKC). These chemokines exhibit potent T-lymphocyte
      chemoattractant activity. DESIGN: Immunohistochemical study. METHODS:
      Conjunctival biopsy specimens from 16 patients with active VKC and nine control
      subjects were studied by immunohistochemical techniques using monoclonal
      antibodies directed against IP-10, Mig, and I-TAC. The phenotype of inflammatory
      cells expressing chemokines was examined by double immunohistochemistry. RESULTS:
      In the normal conjunctiva, very weak Mig immunoreactivity was observed on basal
      epithelial cells and on vascular endothelial cells in the upper substantia
      propria. There was no immunoreactivity for the other chemokines. In all VKC
      specimens, strong immunoreactivity for Mig was expressed by epithelial cells,
      vascular endothelial cells, and inflammatory mononuclear cells. Inflammatory
      mononuclear cells expressing IP-10 and I-TAC were noted in 10 and nine specimens,
      respectively. The numbers of Mig(+) inflammatory cells were significantly higher
      than the numbers of IP-10(+) and I-TAC(+) inflammatory cells (P <.001).
      Inflammatory cells expressing Mig were CD4(+) T-helper/inducer cells (71.6 +/-
      3.2%), CD8(+) T-cytotoxic/suppressor cells (19.5 +/- 1.5%), and CD68(+)
      monocytes/macrophages (5.3 +/- 5%). All inflammatory cells expressing IP-10 and I
      TAC were CD68(+) monocytes/macrophages. CONCLUSIONS: The CXC chemokine Mig is
      selectively and highly expressed in VKC suggesting a pathogenic role of the
      chemokine receptor CXCR3 and the ligand Mig in the recruitment of activated T
      lymphocytes.

PMID- 14597037
TI  - A novel PHOX2A/ARIX mutation in an Iranian family with congenital fibrosis of
      extraocular muscles type 2 (CFEOM2).
AB  - PURPOSE: To describe the clinical features of two affected members of an Iranian
      family with autosomal recessive congenital fibrosis of the extraocular muscles
      (CFEOM2) and to report their novel mutation in the PHOX2A/ARIX gene. DESIGN:
      Experimental study. METHODS:  SETTING: Institutional practice. patient
      population:Six members of an Iranian family with CFEOM underwent complete ocular
      examinations including assessment of ocular motility, visual acuity, slit-lamp
      biomicroscopy, tonometry, and ophthalmoscopy. EXPERIMENTAL PROCEDURE: Mutation
      analysis of the PHOX2A gene was performed using polymerase chain reaction
      amplification of the coding exons and direct sequencing of polymerase chain
      reaction products. MAIN OUTCOME MEASURE: Presence or absence of mutation in
      PHOX2A gene in two siblings with exotropia and recessive CFEOM. Exotropia and
      ptosis were corrected surgically in one of the two siblings. RESULTS: The two
      affected siblings had bilateral ptosis and exotropia and severe limitation of all
      extraocular movements. One patient underwent strabismus surgery and ptosis
      repair. PHOX2A mutation analysis revealed a novel nonsense mutation in exon 2
      (439C-->T). Both parents and the unaffected siblings were heterozygous,and the
      two affected siblings were homozygous for this mutation. CONCLUSIONS: The 439C-
      >T mutation in this family changes a glutamine to a stop codon (Q90X) at the
      beginning of the PHOX2A homeodomain region. This is the fourth CFEOM2 mutation in
      PHOX2A and the first nonsense mutation to be identified. It confirms PHOX2A as
      the autosomal recessive CFEOM2 disease gene and provides evidence that the
      phenotypic differences between PHOX2A mutations in man and mouse do not result
      from hypomorphic PHOX2A alleles in humans.

PMID- 14597038
TI  - Long-term results of frontalis suspension using autogenous fascia lata for
      congenital ptosis in children under 3 years of age.
AB  - PURPOSE: To evaluate the outcome of frontalis suspension surgery for congenital
      ptosis using autogenous fascia lata for children under 3 years of age. DESIGN:
      Retrospective nonrandomized interventional case series. METHODS: This study
      included nine children (14 eyelids) with severe congenital ptosis aged less than
      3 years. All patients underwent frontalis suspension surgery using autogenous
      fascia lata. Postoperative lid level results, ptosis recurrence, and cosmetic
      appearance of leg scars were evaluated after the operation. RESULTS: The mean age
      of the patients was 15.3 months (range, 6 months to 2.5 years) with a mean follow
      up period of 41.6 months (range, 18 to 96 months). All children achieved
      satisfactory cosmetic and functional results, with no postoperative complications
      such as wound infection, corneal exposure, eyelid contour abnormalities, or
      ptosis overcorrection. No recurrence of ptosis was encountered. Harvesting was
      not difficult, and a sufficient amount of material was achieved. There was one
      patient (11.1%) with a hypertrophied leg scar. CONCLUSIONS: Frontalis suspension
      using autogenous fascia is proposed as a possible procedure for correcting
      congenital ptosis in children younger than 3 years of age. It appears to be an
      effective and feasible treatment for children with poor levator muscle function
      in this age group.

PMID- 14597039
TI  - A new mutation (Leu569Arg) within exon 13 of the TGFBI (BIGH3) gene causes
      lattice corneal dystrophy type I.
AB  - PURPOSE: To describe an American family with lattice corneal dystrophy type I,
      which associates with a novel mutation, Leu569Arg, of the TGFBI (BIGH3) gene.
      DESIGN: Experimental study. METHODS: Genomic DNA was extracted from buccal
      epithelial cells of four affected members of an American family with lattice
      corneal dystrophy type I. All 17 exons of the TGFBI gene were evaluated by PCR
      amplification and direct sequencing. Clinical and histologic data were also
      collected. RESULTS: Three generations of this family have been positively
      diagnosed with lattice corneal dystrophy, indicating autosomal dominant
      inheritance. We identified a heterozygous point mutation that associates with the
      disease phenotype. The single base-pair substitution (T1753G) results in an amino
      acid substitution (Leu569Arg) in exon 13 of the TGFBI gene. CONCLUSIONS:
      Substitution of arginine for leucine at position 569 of the TGFBI gene results in
      a form of lattice corneal dystrophy that is phenotypically similar to other
      genetically distinct forms of type I disease. This is the first report of disease
      correlated with changes in exon 13 of the TGFBI gene.

PMID- 14597040
TI  - Anatomical and visual outcome of macular hole surgery with infracyanine green
      assisted peeling of the internal limiting membrane, endodrainage, and silicone
      oil tamponade.
AB  - PURPOSE: To evaluate the anatomical and visual outcome in macular hole patients
      who underwent surgery with infracyanine green-assisted internal limiting membrane
      peeling. DESIGN: A prospective case series with 51 consecutive eyes of 49
      patients with idiopathic, iatrogenic, or traumatic Stage 2, 3, or 4 macular
      holes. METHODS: After removing the vitreous, in all eyes infracyanine green
      assisted removal of the internal limiting membrane was performed. Patients older
      than 65 years of age underwent a simultaneous phacoemulsification. At the end of
      surgery, a silicone oil tamponade was used in all cases, and all patients were
      asked to position face down for 24 hours. Optical coherence tomography was
      performed preoperatively and postoperatively to determine the macular hole
      stage/size and the anatomical closure rate, respectively. RESULTS: The mean
      follow-up time was 9.8 months (range, 6-26 months). The overall median duration
      between the first symptoms and the surgery was 5 months. The overall anatomical
      success rate after one surgery was 92% (47 eyes), while that of chronic and
      nonchronic ones was 72.3% and 97.5%, respectively. The median preoperative visual
      acuity was 20/160 (range, 20/30 to counting fingers) and increased to 20/50
      (range, 20/20 to 20/400) postoperatively. The mean increase in visual acuity was
      3.7 lines (range, -4 to 10 lines). Of all 51 operated-on eyes, 26 (51%) eyes had
      a final visual acuity of 20/50 or better. CONCLUSIONS: These findings indicate
      that infracyanine green-assisted removal of the retinal internal limiting
      membrane appears to induce a high incidence of anatomical closure, with good
      visual outcome.

PMID- 14597041
TI  - Relationship of optic disk topography and visual function in patients with large
      cup-to-disk ratios.
AB  - PURPOSE: To determine if topographic differences exist between large cup-to-disk
      ratio (C/D) eyes with standard achromatic automated perimetry (SAP) abnormalities
      and those with only short-wavelength automated perimetry (SWAP) abnormalities.
      DESIGN: Cross-sectional study. METHODS: The setting was a referral university
      based clinical practice. We selected one eye of 72 patients with a vertical C/D
      of at least 0.8 by ophthalmoscopy. Patients performed SWAP, SAP, and confocal
      scanning laser ophthalmoscopy. We compared optic disk topography in eyes with and
      without visual field abnormalities and controlled for the influence of disk area.
      RESULTS: Disk area was a confounder of many topographic measures. After
      controlling for disk area, eyes with abnormal SAP had differences in rim volume,
      cup shape, rim area, retinal nerve fiber layer thickness, and retinal nerve fiber
      layer cross-sectional area when compared with eyes with normal SAP (P <.05). Rim
      volume and rim area were different in the SWAP comparison (P <.05). CONCLUSIONS:
      Investigators should control for disk area when evaluating topographic measures
      by confocal scanning laser ophthalmoscopy. In eyes with a large C/D, optic disk
      topography is more glaucomatous in eyes with SAP abnormalities than in those with
      only SWAP abnormalities. Eyes with large C/D and only SWAP abnormalities may have
      fewer glaucomatous optic disk changes than such eyes with SAP abnormalities. This
      indicates that SWAP is likely to correspond to abnormalities in optic disk
      topography at an earlier stage of glaucomatous optic neuropathy than SAP.
      Therefore, clinicians should consider SWAP testing in glaucoma suspects to detect
      glaucomatous visual field loss at an earlier stage of structural loss.

PMID- 14597042
TI  - Management of macular holes that develop after retinal detachment repair.
AB  - PURPOSE: To study the characteristics and management of macular holes that
      develop after prior rhegmatogenous retinal detachment (RD) repair. DESIGN:
      Retrospective, interventional, consecutive case series. METHODS: The setting was
      a clinical practice. The case records of all of our patients (n = 12) who
      developed a new full-thickness macular hole after prior RD repair over an 8-year
      period were examined. Patients who developed a macular hole after prior RD repair
      were offered either surgical repair of the macular hole or continued observation.
      For eyes that underwent macular hole repair, main outcome measures included
      macular attachment status and postoperative visual acuity. RESULTS: Twelve full
      thickness macular holes were detected in a series of 2,380 eyes (0.5%
      prevalence), which had undergone surgery for prior primary RD. Ten macular holes
      developed after scleral buckling surgery, two after pneumatic retinopexy, and
      none were seen after primary vitrectomy. The fovea had been detached in 11 of the
      12 eyes at the time of RD. The median time to macular hole diagnosis after RD
      repair was 3.4 months (range, 0.3-161 months). Eight of the eight eyes (100%)
      undergoing surgical repair achieved macular reattachment with a median of 3.5
      lines of visual improvement at a median of 14.8 months of follow-up. Seven of
      these eight eyes had an improvement in visual acuity of at least 3 Snellen lines,
      and four of the eight had at least 20/40 visual acuity postoperatively. Four eyes
      with macular holes were observed. CONCLUSIONS: Macular holes developed in less
      than 1% of eyes that had previously undergone repair of rhegmatogenous RD. In our
      series, these atypical holes were seen predominantly after macula-off
      detachments, most commonly occurring after scleral buckling procedures. They were
      effectively repaired using conventional pars plana vitrectomy with long-acting
      gas tamponade and a variety of adjuvant therapies. A good visual outcome is
      possible with this approach.

PMID- 14597043
TI  - Anterior chamber depth in plateau iris syndrome and pupillary block as measured
      by ultrasound biomicroscopy.
AB  - PURPOSE: To quantitatively analyze the anterior chamber depth (ACD) in patients
      with pupillary block and plateau iris syndrome. DESIGN: Retrospective,
      consecutive, observational case series. METHODS: We measured the ACD in 318 eyes
      of 318 patients who had been diagnosed by ultrasound biomicroscopy as having
      either pupillary block or plateau iris syndrome. Pupillary block patients were
      all preiridotomy and plateau iris patients were all postiridotomy. Anterior
      chamber depth was measured axially from the internal corneal surface to the lens
      surface using the ultrasound instrument's internal measuring capability. RESULTS:
      The mean ACD in patients with plateau iris syndrome (n = 181) was significantly
      smaller than the hypothesized normal ACD (2.04 +/- 0.30 mm vs 3.0 mm, P =.0001).
      The mean ACD in patients with pupillary block (n = 137) was also significantly
      smaller than the hypothesized normal ACD (2.17 +/- 0.30 mm vs 3.0 mm, P =.0001).
      The mean ACD in patients with plateau iris syndrome was significantly smaller
      than the ACD in patients with pupillary block (2.04 +/- 0.30 mm vs 2.17 +/- 0.30
      mm, P =.001). CONCLUSIONS: Review of the literature suggests that patients with
      plateau iris have a normal or deeper axial ACD compared with pupillary block.
      This study found that the ACD associated with plateau iris syndrome is shallower
      than normal and also shallower than in pupillary block.

PMID- 14597044
TI  - Evaluation of optineurin sequence variations in 1,048 patients with open-angle
      glaucoma.
AB  - PURPOSE: To investigate the association of sequence variations in the optineurin
      (OPTN) gene in patients with open-angle glaucoma. DESIGN: Prospective case
      control study. METHODS: The OPTN gene was screened for sequence variations using
      a combination of single-strand conformational polymorphism analysis and automated
      DNA sequencing. A total of 1,299 subjects (1048 glaucoma patients and 251
      controls) were screened for variations in the four portions of the gene that had
      been previously associated with glaucoma. A subset of these subjects (376
      patients and 176 controls) was screened for variations in the entire coding
      sequence. Twenty-four percent of the patients and 35% of the controls were
      Japanese, whereas the remainder were predominantly Caucasian. Allele frequencies
      were compared with the Fisher exact test. RESULTS: The OPTN sequence variations
      were not significantly associated with any form of high-tension open-angle
      glaucoma. One proband with familial normal-tension glaucoma was found to harbor
      the previously reported Glu50Lys variation. Another previously reported change,
      Met98Lys, was associated with normal-tension glaucoma in Japanese but not in
      Caucasian patients. CONCLUSIONS: This study provides some additional evidence for
      the association of the Glu50Lys OPTN sequence variation with familial normal
      tension glaucoma. However, because familial normal-tension glaucoma is so rare,
      this change seems to be responsible for less than 0.1% of all open-angle
      glaucoma. The Arg545Gln variation is likely to be a nondisease-causing
      polymorphism. The Met98Lys change may be associated with a fraction of normal
      tension glaucoma in patients of Japanese ethnicity.

PMID- 14597047
TI  - Intravitreal triamcinolone and endophthalmitis.

PMID- 14597045
TI  - Haptoglobin phenotype in age-related macular degeneration patients.
AB  - PURPOSE: To investigate a possible role of the haptoglobin phenotype in the
      development of exudative age-related macular degeneration (AMD) in human
      subjects. DESIGN: Prospective, observational, comparative population study.
      METHODS: The study was carried out in an institutional setting. All patients
      referred because of exudative AMD in one eye during an 18-month period were
      included in the study group. A group of patients treated for other ocular
      diseases and not having AMD in either eye served as control. Haptoglobin
      phenotype was determined from a blood sample drawn from each patient in both the
      study and control groups. The main outcome measure was the distribution of the
      haptoglobin phenotype in the study and control group. RESULTS: One hundred eighty
      five participants were included in the study. Ninety-eight had exudative AMD, and
      87 were AMD-free. The difference between the study and control groups in
      distribution of the haptoglobin phenotype was found to be statistically
      insignificant. CONCLUSIONS: Our results suggest that the haptoglobin phenotype
      has no effect on the prevalence of exudative AMD.

PMID- 14597048
TI  - Factors that predict the benefit of lowering intraocular pressure in normal
      tension glaucoma.

PMID- 14597049
TI  - Professionalism: questions, old and new.

PMID- 14597050
TI  - A modified laser test for the identification of retinoschisis.
AB  - PURPOSE: To describe a modified laser technique for identification of bullous
      retinoschisis. DESIGN: Retrospective interventional case series collected over 10
      years. METHODS: Forty-one eyes with presumed bullous retinoschisis and breaks in
      the inner layers underwent a low-energy argon green laser application at the same
      energy as a control spot in adjacent retina. A gray response in the outer layers
      equal to the control spot was diagnostic of retinoschisis. RESULTS: The laser
      test was positive for retinoschisis in 40 of 41 eyes. In none of the 40 eyes did
      the elevation progress. CONCLUSIONS: A low-energy argon green laser application
      through a break in the inner layers of presumed retinoschisis eliminates the
      attenuation of the beam and can confirm retinoschisis.

PMID- 14597051
TI  - Symptomatic cicatrizial occlusion of canaliculi after insertion of Herrick
      lacrimal plugs.
AB  - PURPOSE: To report severe symptomatic complications following bilateral insertion
      of Herrick lacrimal plugs. DESIGN: Interventional case report. METHODS: Bilateral
      clinical, surgical, and histologic findings in a patient with surgical revision
      of canaliculi after plug insertion. RESULTS: A 55-year-old patient presented with
      recurrent inflammation, discharge, and epiphora 24 months after insertion of
      lacrimal plugs; surgical intervention and partial resection of the cicatrized
      canaliculi was necessary. Light microscopic histology revealed canaliculi
      destruction, reactive tissue embedding of the plugs, and dissociated plug
      material. CONCLUSIONS: The application of Herrick lacrimal plugs may not be
      reversible and may require invasive surgical intervention.

PMID- 14597052
TI  - Occlusive vasculitis in a patient with concomitant West Nile virus infection.
AB  - PURPOSE: To describe a patient with occlusive, retinal vasculitis and
      concomitant, confirmed, acute West Nile virus (WNV) infection. DESIGN:
      Observational case report. METHODS: Main outcome measures included comprehensive
      ophthalmic examination with fluorescein angiography, color photography, and
      serologic testing for WNV and St. Louis encephalitis (SLE) virus including plaque
      reduction neutralization testing (PRNT). RESULTS: A 46-year-old woman developed a
      sudden decrease in vision in her left eye 2 weeks after confirmed WNV infection
      and demonstrated multiple, small, patchy areas of retinal edema with scattered
      microaneurysms. Fluorescein angiography showed multiple branch artery occlusions
      with extensive nonperfusion. Serologic titers for WNV were positive for acute
      infection. Plaque reduction neutralization testing confirmed WNV infection and
      excluded St. Louis encephalitis virus infection. Other etiologies of occlusive
      vasculitis were not present. CONCLUSIONS: Occlusive, retinal vasculitis may occur
      in the setting of acute WNV infection.

PMID- 14597053
TI  - Diabetic retinopathy with repeated amaurosis fugax caused by orthostatic
      hypotension.
AB  - PURPOSE: To evaluate the blood flow velocity in the ophthalmic artery using color
      Doppler imaging in two patients who had diabetic retinopathy with amaurosis fugax
      caused by orthostatic hypotension. DESIGN: Interventional case reports. METHODS:
      A 40-year-old woman (Case 1) and a 65-year-old man (Case 2) had diabetic
      retinopathy and amaurosis fugax caused by orthostatic hypotension. We evaluated
      the blood flow velocity in the ophthalmic artery using color Doppler imaging in
      the two patients. SETTING: Department of Ophthalmology, Diabetes Center Tokyo
      Women's Medical University, Tokyo, Japan. RESULTS: For Case 1, the maximum
      systolic blood flow velocity in the ophthalmic artery (V max) was 10 cm/sec in
      the supine position. In a seated position, visual acuity was decreased from 20/20
      to light perception as V max fell to 1 cm/sec. For Case 2, the V max was 14
      cm/sec in the supine position, but it was too low to measure in a seated
      position. CONCLUSIONS: The decrease of V max by orthostatic hypotension may cause
      amaurosis fugax in patients with diabetic retinopathy.

PMID- 14597054
TI  - 10-year follow-up study of secondary transscleral ciliary sulcus fixated
      posterior chamber intraocular lenses.
AB  - PURPOSE: To study the outcome of transscleral ciliary sulcus fixated posterior
      chamber intraocular lenses (transscleral fixation of PC IOLs) at 10 years after
      surgery. DESIGN: Longitudinal observational study. METHODS: A total of 16
      patients (16 eyes) who had undergone transscleral fixation of PC IOL were
      studied. We evaluate the clinical outcome in each patient at 10 years after the
      operation. SETTING: The Department of Ophthalmology, University of Tokyo Graduate
      School of Medicine, Tokyo, Japan. RESULTS: Visual loss and other complications
      occurred within 2 years of the operation but not later. Postoperative
      complications were cystoid macular edema in three eyes (18.8%) and age-related
      macular degeneration in one eye (6.3%). CONCLUSIONS: It is important to carefully
      observe and adequately treat patients for 2 years postoperatively.

PMID- 14597055
TI  - Uveitis in patients with sarcoidosis is not associated with mutations in NOD2
      (CARD15).
AB  - PURPOSE: Mutations in NOD2 are responsible for Blau syndrome, a systemic disease
      triad involving the uvea, joints, and skin. NOD2 mutations are also associated
      with Crohn disease. Both Blau syndrome and Crohn disease involve granulomatous
      inflammation and uveitis, as does sarcoidosis. We sought to determine if NOD2
      mutations were present in patients with sarcoidosis, especially those with
      uveitis. METHODS: NOD2 gene exons were sequenced from DNA obtained from
      sarcoidosis patients. The diagnoses of sarcoidosis and uveitis were verified from
      clinical records. RESULTS: NOD2 polymorphisms were found in 26 patients with
      sarcoidosis (13 with uveitis). There was no significant difference in allele
      frequencies between patients with and without uveitis. CONCLUSIONS: Despite the
      strikingly similar pathologies of Blau syndrome and sarcoidosis, no mutations
      were found to be associated with sarcoidosis in a group of patients, regardless
      of the presence of uveitis.

PMID- 14597057
TI  - Laminated posterior vitreous cortex associated with idiopathic macular hole.
AB  - PURPOSE: To report an unusual preretinal opacity associated with an idiopathic
      macular hole (MH) that was identified by optical coherence tomography. DESIGN:
      Observational case report. METHODS: A 59-year-old woman with a preretinal linear
      opacity running across an MH was examined by optical coherence tomography.
      RESULTS: Optical coherence tomography showed a full-thickness MH with a
      superiorly hinged flap. The preretinal opacity was identified as a part of a
      laminated vitreous cortex that was perpendicularly attached to the apex of the
      flap. A horizontal scan showed a partly double-layered posterior vitreous cortex.
      Two months later, the linear opacity disappeared coincident with a complete
      posterior vitreous detachment. The MH was closed by vitrectomy with peeling of
      the internal limiting membrane. CONCLUSIONS: Optical coherence tomography
      identified an unusual ophthalmoscopic presentation of a preretinal opacity as a
      part of laminated vitreous cortex associated with a "can-opener" MH.

PMID- 14597056
TI  - Technique to alter field of view during vitrectomy with phacoemulsification and
      aspiration in gas-filled eye.
AB  - PURPOSE: To describe a method to alter the angular field of view of the fundus in
      gas-filled eyes during pars plana vitrectomy and phacoemulsification with
      aspiration and intraocular lens implantation. v Description of a new surgical
      method. METHODS: The amount of viscoelastic material injected into the capsule is
      regulated, altering posterior capsule curvature. RESULTS: The visual field can be
      varied from 5 to 108 degrees. Surgery on more than 300 eyes with rhegmatogenous
      retinal detachment and cataract using this technique has been successful with no
      complications. CONCLUSIONS: This method effectively controls the field of view in
      gas-filled eyes.

PMID- 14597058
TI  - Langerhans cell histiocytosis with periorbital cellulitis.
AB  - PURPOSE: To report a case of Langerhans cell histiocytosis presenting as
      periorbital cellulitis. DESIGN: Interventional case report. METHODS: A 3-year-old
      girl presented with periorbital swelling of the right upper lid laterally of two
      days' duration. A history of recent eye trauma was reported. RESULTS: Computed
      tomography showed a soft tissue mass that eroded the frontozygomatic suture. The
      lesion was debulked through a lateral orbitotomy. Electron microscopy disclosed
      Birbeck granules. Immunohistochemistry stained positively for CD68 and CD1a
      antigenic determinants. CONCLUSIONS: Although rare, Langerhans cell histiocytosis
      can cause acute periorbital cellulitis in children. Trauma can induce an
      inflammatory response, allowing for earlier diagnosis of the orbital lesion.

PMID- 14597059
TI  - Intrusion of an encircling buckle after retinal detachment surgery.
AB  - PURPOSE: To report a patient with intrusion of the encircling buckle late
      postoperatively after surgical treatment of a rhegmatogenous retinal detachment.
      DESIGN: Interventional case report. METHODS: We performed an encircling buckle
      procedure on a 77-year- old woman with a rhegmatogenous retinal detachment. Four
      years after the operation, the encircling buckle intruded into the vitreous
      cavity. RESULTS: After 3 months of diagnosis of the intrusion, the retina was
      detached totally. CONCLUSIONS: Intrusion of the encircling buckle without any
      additional segmental buckling element is a very rare late complication of retinal
      detachment surgery.

PMID- 14597060
TI  - An unusual complication from esthetic injection of liquid silicone into the
      forehead.
AB  - PURPOSE: To report a case of migration of liquid silicone into the upper eyelid.
      DESIGN: Interventional case report. METHODS: A 32-year-old woman had an injection
      of liquid silicone into the subcutaneous tissue of the forehead. She developed a
      cystic mass in the upper eyelid 2 days postinjection. An excisional biopsy was
      performed. RESULTS: The mass lay in the Muller's muscle, and its base adhered to
      the tarsus. The mass ruptured during dissection, revealing a yellowish turbid
      fluid. Histopathologic findings showed lipogranulomatous reaction. CONCLUSIONS:
      Liquid silicone injection to the forehead may promote formation of a cystic mass
      in the upper eyelid.

PMID- 14597061
TI  - Buphthalmos in the setting of persistent hyperplastic primary vitreous cataract.
AB  - PURPOSE: To report a case of unilateral persistent hyperplastic primary vitreous
      cataract presenting with ipsilateral buphthalmos. DESIGN: Retrospective case
      report. METHODS: The patient chart was reviewed, and a relevant literature search
      was performed. RESULTS: A four-month-old child presented with persistent
      hyperplastic primary vitreous cataract in the right eye and ipsilateral
      buphthalmos with no discernable angle abnormalities. He underwent lensectomy,
      anterior vitrectomy, and limited transscleral diode cyclodestruction in the right
      eye. CONCLUSIONS: This appears to be the first report of buphthalmos presenting
      with unilateral persistent hyperplastic primary vitreous. Despite two
      comorbidities, the patient has thus far responded well to initial treatment and
      visual rehabilitation.

PMID- 14597062
TI  - Limitation of opposing ductions following augmented horizontal rectus muscle
      transposition.
AB  - PURPOSE: To report the effect on ductions in opposing gaze following augmented
      horizontal rectus muscle transposition to treat cyclovertical muscle palsies.
      METHODS: Record review of 5 patients who underwent augmented horizontal rectus
      muscle transposition for treatment of vertical gaze misalignment secondary to
      cyclovertical muscle palsy. RESULTS: Ductions in the direction of the palsied
      muscle improved in all patients. Four patients (80%) developed significant
      limitation of vertical gaze in the direction opposite that of the palsied muscle.
      CONCLUSIONS: Augmented transposition surgery for vertical muscle palsy can
      produce considerable limitation of ductions in the direction opposite to that of
      the paralyzed muscle.

PMID- 14597063
TI  - Clinical agreement among glaucoma experts in the detection of glaucomatous
      changes of the optic disk using simultaneous stereoscopic photographs.
AB  - PURPOSE: To evaluate the clinical agreement in the detection of optic disk
      changes in patients with glaucoma using simultaneous stereophotographs. DESIGN:
      Masked-observer variability study. METHODS: Ten glaucoma specialists examined
      pairs of simultaneous stereophotographs of glaucomatous and control optic disks
      to determine whether there were changes compatible with progression of
      glaucomatous damage. RESULTS: Intraobserver agreement had a kappa value ranging
      from 0.55 to 0.78. Interobserver agreement among the glaucoma specialists had a
      kappa value ranging from 0.34 to 0.68. CONCLUSIONS: Clinical examination of
      stereophotographs to detect optic disk changes in glaucoma patients has
      limitations associated with suboptimal reproducibility.

PMID- 14597064
TI  - Rapid onset childhood cataracts leading to the diagnosis of autoimmune
      polyendocrinopathy-candidiasis-ectodermal dystrophy.
AB  - PURPOSE: To report a case of bilateral cataracts in a child that led to diagnosis
      of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. DESIGN:
      Observational case report. METHODS: A 12-year-old boy was being investigated for
      weakness, lethargy, short stature, and blurred vision. He developed bilateral,
      dense cataracts over a 2-week period. He was found to be hypocalcemic and
      diagnosed with hypoparathyroidism and autoimmune polyendocrinopathy-candidiasis
      ectodermal dystrophy. RESULTS: Because of hypoparathyroidism, adrenocortical
      failure, and insulin-dependent diabetes, it was 9 months before the patient's
      metabolic imbalance was brought under sufficient control to allow cataract
      surgery. CONCLUSIONS: Autoimmune polyendocrinopathy-candidiasis-ectodermal
      dystrophy should be considered with diagnoses of hypocalcemic cataract.

PMID- 14597065
TI  - Exudative retinal detachment due to small noncalcified retinal astrocytic
      hamartoma.
AB  - PURPOSE: To report a case of exudative retinal detachment due to small
      noncalcified retinal astrocytic hamartoma and review pertinent literature.
      DESIGN: Case report and review of literature. METHODS: Clinical examination,
      fluorescein angiography, optical coherence tomography, and laser treatment were
      performed. RESULTS: Exudative macular detachment caused by a small noncalcified
      retinal astrocytic hamartoma confirmed by optical coherence tomography regressed
      completely after laser therapy. Visual acuity improved only slightly because
      lamellar macular thinning developed after subretinal fluid and macular exudates
      resolved. CONCLUSIONS: Small noncalcified, parafoveal retinal astrocytic
      hamartomas may cause macular retinal detachment. Optical coherence tomography may
      aid in the diagnosis of the tumor. Argon laser photocoagulation may induce tumor
      regression and resolution of exudative detachment. Final visual acuity may be
      limited in some cases.

PMID- 14597066
TI  - TIMP-3 mRNA is not overexpressed in Sorsby fundus dystrophy.
AB  - PURPOSE: To assess the expression of MMP (matrix metalloproteinase)-2 and -9 and
      TIMP (tissue inhibitors of metalloproteinases)-1, -2, and -3 in Sorsby fundus
      dystrophy. DESIGN: Cliniciopathological report. METHODS: A donor eye with a
      confirmed S181C mutation in the TIMP-3 gene and an age-matched normal donor eye
      were studied using in situ hybridization technique with MMP -2 and -9 and TIMP 
      1, -2, and -3 probes. RESULTS: There is a reduction of mRNA expression of MMP-2
      and TIMP-3 in the Sorsby retinal pigment epithelium cells. CONCLUSIONS: Increased
      expression of TIMP-3 mRNA does not cause accumulation of TIMP-3 in the Bruch
      membrane of Sorsby fundus dystrophy nor is it likely to cause age-related macular
      degeneration.

PMID- 14597067
TI  - Questionnaire survey on periodic ocular examination in Japanese diabetic
      patients.
AB  - PURPOSE: To identify the reasons why diabetic patients do not undergo periodic
      examination. DESIGN: Cohort study. METHODS: A questionnaire survey of 1,333
      Japanese type 2 diabetic patients was conducted at Tokyo Women's Medical
      University. Performance of ocular examinations was investigated over 5 years and
      the reasons for not undergoing examination were analyzed. RESULTS: Periodic
      ocular examination was performed in 69.5% of patients, but not in 30.5%. The
      questionnaire survey showed that physicians usually explained the risk of ocular
      complications and recommended periodic examination. More than 98% of the patients
      were aware of diabetic eye disease. Multivariate logistic regression analysis
      showed the main reason for skipping examination as a reason was that patients
      believed they had no diabetic retinopathy. CONCLUSIONS: Patients should be
      informed about the necessity of receiving periodic ocular examination even if
      they do not yet have retinopathy.

PMID- 14597068
TI  - Bilateral corneal neovascularization and opacification associated with
      unmonitored contact lens wear.
AB  - PURPOSE: To report a case of severe bilateral deep stromal neovascularization and
      opacification associated with unmonitored contact lens wear. DESIGN:
      Observational case report. METHODS: A 46-year-old woman who had been using
      hydrogel contact lenses bought on the Internet without a prescription for 5 years
      was found to have dense, bilateral corneal opacities with deep stromal
      neovascularization. RESULTS: The patient's contact lenses were found to be tight
      fitting. Medical history and serological studies were negative for infectious or
      rheumatologic causes of interstitial keratitis. CONCLUSIONS: The deep stromal
      neovascularization and the associated corneal opacification are most likely
      related to the unmonitored contact lens use and the lack of routine eye
      examinations. We believe it is critical that all contact lens wearers receive
      professional eye care on a regular basis regardless of where they obtain their
      contact lens supplies.

PMID- 14597069
TI  - Unilateral uveitis induced by a nonionic iodinated contrast agent.
AB  - PURPOSE: To report recurrent unilateral uveitis after computed tomography (CT)
      enhanced by the contrast agent iopamidol. DESIGN: Observational case report.
      METHODS: A 44-year-old man with a history of mixed-cellularity Hodgkin lymphoma,
      Stage I B (axillar, infraclavicular, subpectoral lymphomas) was under remission
      after chemotherapy and radiotherapy. The contrast-enhanced CT scans performed
      every 3 months were within hours followed by a marked unilateral anterior
      uveitis, vitritis, and retinal bleedings. Symptoms resolved with topical
      corticosteroid treatment within a week. RESULTS: We observed recurrent unilateral
      uveitis after intravenously application of 150 ml of iopamidol for contrast
      enhanced CT scans in a patient with lymphoma in remission. CONCLUSIONS: Iopamidol
      may induce uveitis under certain circumstances. We suggest a coincidence of
      immunologic mechanisms with predisposing discrete vascular radiation damage.

PMID- 14597070
TI  - Intraoperative light toxicity: a possible explanation for the association between
      cataract surgery and age-related macular degeneration.

PMID- 14597071
TI  - Indocyanine green-assisted peeling of the internal limiting membrane in macular
      hole surgery affects visual outcome: a clinicopathological correlation.

PMID- 14597073
TI  - Adult-onset foveomacular vitelliform dystrophy: a study by optical coherence
      tomography.

PMID- 14597075
TI  - Corneal thickness measurements and visual function abnormalities in ocular
      hypertensive patients.

PMID- 14597077
TI  - Migration and apparent disappearance of silicone tube after treatment of
      nasolacrimal duct obstruction.

PMID- 14597093
TI  - Expression of soma-restricted proteolipid/DM20 proteins in lymphoid cells.
AB  - A new family of the myelin proteolipid protein (PLP/DM20) gene products,
      srPLP/DM20, has been identified recently in thymus and brain. In the central
      nervous system, srPLP/DM20 products are not localized in the myelin membrane,
      unlike their classic PLP/DM20 counterparts. In the immune system, the classic
      PLP/DM20 products appear to be expressed predominantly in thymic cortical
      epithelium. In this study, we examined the cellular expression of sr-PLP/DM20
      proteolipids in lymphoid tissues and cells by immunohistochemistry, FACS analysis
      and RT-PCR. We found that in contrast to the classic PLP/DM20 products, sr
      proteins are mainly expressed in developing thymocytes in thymus and in T- and B
      lymphocytes in spleen. These results are of importance in our further
      understanding, not only the different role of these new PLP gene products in
      central and peripheral tolerance, but also the function of such products in
      lymphocyte biology.

PMID- 14597092
TI  - Retinal pigment epithelial cells activate uveitogenic T cells when they express
      high levels of MHC class II molecules, but inhibit T cell activation when they
      express restricted levels.
AB  - The retinal pigment epithelium (RPE) plays an important role in maintaining the
      privileged status of the eye. In this study, we examined the outcome of the in
      vitro interaction between uveitogenic T cells and non-activated or activated RPE
      cells. An interphotoreceptor retinoid-binding protein (IRBP)-reactive T cell line
      was established and RPE cell monolayers prepared. The expression of MHC class II
      molecules on RPE cells activated by graded doses of IFN-gamma was determined by
      flow cytometry. Proliferation and cytokine production of IRBP-reactive T cells
      were measured after exposure to IFN-gamma-activated RPE cells. We found that RPE
      cells expressed various levels of MHC class II molecules depending on the
      concentration of IFN-gamma used. IRBP-specific T cells could be stimulated or
      inhibited by exposure to RPE cells. The dual effect of RPE cells might be
      regulated via different levels of MHC class II molecules on the RPE cells. It
      suggests that controlling the immune activities of uveitogeneic T cells by
      varying the levels of MHC class II expression on the RPE might be one of the
      regulatory mechanisms by which the RPE maintains immune privilege in the eye.

PMID- 14597094
TI  - Withdrawal from morphine in mice suppresses splenic macrophage function, cytokine
      production, and costimulatory molecules.
AB  - We have previously shown that abstinence from morphine by either abrupt (AW) or
      precipitated (PW) withdrawal induces greater than 80% suppression in the capacity
      to mount an in vitro plaque-forming cell (PFC) response to sheep red blood cells
      at 24-h post withdrawal. Present studies on the mechanisms of immunosuppression
      showed that addition of normal unfractionated spleen cells, macrophage-enriched
      adherent cells, or CD11b(+) purified macrophages, to spleen cells taken from
      withdrawn mice, restored immune responses. Spleen cells from mice undergoing
      withdrawal also had decreased splenic mRNA and/or protein levels of IL-1beta, IL
      1Ra, TNF-alpha, IL-12, and IFN-gamma. Addition of IL-1beta or IFN-gamma to AW
      cultures was able to reverse their immunosuppression. These results strongly
      suggest that morphine withdrawal results in a deficit of macrophage function.

PMID- 14597095
TI  - Action of treosulfan in myelin-oligodendrocyte-glycoprotein-induced experimental
      autoimmune encephalomyelitis and human lymphocytes.
AB  - Treosulfan (dihydroxybusulfane, DHB, L-threitol-1,4-bis [methane sulfonate]) is a
      cytostatic alkylating agent with a favorable profile of side effects. Myelin
      oligodendrocyte-glycoprotein (MOG)-induced experimental autoimmune
      encephalomyelitis (EAE) induced in DA (RT1(av1)) rats resembles multiple
      sclerosis (MS) in many aspects since central nervous system (CNS) pathology shows
      inflammation, demyelination and axonal loss. Moreover, DA rats develop a chronic
      disease course. We here explored the efficacy of treosulfan in the treatment of
      MOG-induced EAE in DA rats. A single dose of treosulfan (1 g/kg body weight i.p.)
      at the day of immunization significantly reduced disease severity compared with
      PBS-treated controls. In addition, after disease had evolved, a single dose of
      treosulfan (1 g/kg body weight) given i.p. on day 14 post-immunization (p.i.)
      improved long-term disease outcome. Treatment with treosulfan resulted in reduced
      mRNA expression of IL-12 and interferon (IFN)-gamma in draining lymph nodes and
      reduced numbers of IFN-gamma-secreting MOG-specific T cells. No myelosuppression
      was observed. Treosulfan was applied to different subsets of cultured human blood
      mononuclear cells in order to asses the effects on human immune cells in vitro:
      Treosulfan reduced proliferative capacity and increased apoptosis in T cells and
      antigen-presenting cells. In light of the beneficial effects in EAE in vivo and
      the in vitro immunosuppressive and pro-apoptotic capacities in cultured human
      mononuclear immune effector cells, these data may support a potential role of
      treosulfan, an agent with high immunosuppressive capacity and low toxicity, in
      the treatment of MS.

PMID- 14597096
TI  - Generation of antibodies against prion protein in wild-type mice via helix 1
      peptide immunization.
AB  - We present here the development of antibodies against prion protein in BALB/C
      mice using as antigen human helix 1 of PrP. This sequence is suggested to be
      involved in protein pathological conformational changes, and is distinguished
      from that of mice by one amino acid. The immune tolerance to an 'almost-self'
      epitope and the poor immunogenicity of short peptides was overcome by using
      Multiple Antigen Peptide displaying eight copies of helix 1. The generated
      antibodies recognize the whole prion protein with a high binding constant and the
      established protocol may lead to an active immunization towards therapeutics of
      prion disease.

PMID- 14597097
TI  - The endogenous, immunologically active peptide apelin inhibits lymphocytic
      cholinergic activity during immunological responses.
AB  - We investigated the effects of apelin, an immunologically active peptide ligand
      for orphan receptor APJ, on acetylcholine (ACh) synthesis in MOLT-3 human
      leukemic T cells. We initially confirmed expression of APJ mRNA in several human
      T- and B-cell lines by reverse transcription-polymerase chain reaction (RT-PCR).
      We also found that in phytohemagglutinin (PHA)-stimulated MOLT-3 cells, an active
      apelin fragment, apelin-13, down-regulates expression of choline
      acetyltransferase (ChAT) mRNA and significantly reduces ChAT activity and
      cellular ACh content and release. It thus appears that apelin inhibits
      lymphocytic cholinergic activity via APJ during immunological responses.

PMID- 14597098
TI  - Acute and chronic stress exert opposing effects on antibody responses associated
      with changes in stress hormone regulation of T-lymphocyte reactivity.
AB  - Here we show that stress exerts a differential effect on T-cell-dependent
      antibody production. IgG production is augmented after acute stress and impaired
      in a chronic situation. We found catecholamines and corticosterone levels were
      increased in acute situations although they were not modified after prolonged
      stress conditions. However, lymphocyte sensitivity to corticosterone and
      catecholamines was altered under stress conditions. These results point out the
      role of the adrenal's hormones as mediators of the differential effects of stress
      on the immune response providing the basis for a functional significance of
      stress hormone receptors on lymphocytes.

PMID- 14597099
TI  - A dual role for interleukin-1 in LTP in mouse hippocampal slices.
AB  - Interleukin-1 (IL-1) exerts numerous effects in the central nervous system and
      has been implicated in synaptic plasticity. The objective of this study was to
      investigate the role of endogenous as well as exogenous IL-1 on long-term
      potentiation (LTP). Hippocampal slices incubated at 34-36 degrees C show enhanced
      levels of IL-1alpha and IL-1beta compared to slices incubated at 21-24 degrees C.
      IL-1 inhibits LTP induced by theta-burst stimulation (TBS) at either temperature.
      IL-1 receptor antagonist (IL-1ra) had no effect on LTP at 21-24 degrees C, but
      displayed a concentration-dependent inhibition of LTP at 34-36 degrees C. Under
      control conditions, the magnitude of LTP was not temperature dependent. These
      data suggest that IL-1 is required for LTP under physiological conditions but at
      higher doses, as encountered in pathological conditions, IL-1 inhibits LTP.

PMID- 14597100
TI  - Microglia are activated to become competent antigen presenting and effector cells
      in the inflammatory environment of the Theiler's virus model of multiple
      sclerosis.
AB  - Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD)
      is a well-characterized murine model of the chronic-progressive form of human
      multiple sclerosis (MS) characterized by the activation of myelin-specific
      autoreactive CD4 Th1 cells via epitope spreading. To gain an understanding of the
      potential role of central nervous system (CNS)-resident cells in the presentation
      of endogenous myelin epitopes, we determined the individual antigen presentation
      and effector potential of resident microglia vs. infiltrating macrophages in the
      CNS of mice with ongoing TMEV-IDD by performing functional analysis of these
      populations separated to high purity by flow cytometric sorting based on their
      level of CD45 expression. Unlike microglia from nai;ve mice, peptide-pulsed
      CD45(lo) microglia isolated at the onset of clinical disease were as efficient as
      CNS-infiltrating CD45(hi) macrophages in activating proliferation and IFN-gamma
      production by myelin-peptide specific Th1 cells. In contrast, during the chronic
      stages of TMEV-IDD, CNS-infiltrating macrophages were more highly activated than
      the resident microglia as reflected both by higher expression of cell surface
      molecules associated with APC function and enhanced functional ability of spinal
      cord-infiltrating macrophages to stimulate T cell proliferation in vitro.
      Interestingly, both microglia and infiltrating macrophages expressed similar
      profiles of effector molecules such as IL-1, IL-6, IL-12 p40, TNF-alpha, and
      iNOS. Collectively, this is the first report comparing the antigen-presenting
      phenotype and function of microglia and infiltrating macrophages in a virus
      induced model of CNS demyelination demonstrating that the resident microglia are
      capable APCs and may play an important role in antigen presentation at the onset
      of clinical disease and contribute to effector myelin destruction.

PMID- 14597101
TI  - Interleukin-1 beta and lipopolysaccharide decrease soluble guanylyl cyclase in
      brain cells: NO-independent destabilization of protein and NO-dependent decrease
      of mRNA.
AB  - We previously showed that soluble guanylyl cyclase (sGC) is down-regulated in
      astroglial cells after exposure to LPS. Here, we show that this effect is not
      mediated by released IL-1beta but that this cytokine is also able to decrease NO
      dependent cGMP accumulation in a time- and concentration-dependent manner. The
      effect of IL-1beta is receptor-mediated, mimicked by tumor necrosis factor-alpha
      and involves a decrease in sGC activity and protein. IL-1beta and LPS decrease
      the half-life of the sGC beta1 subunit by a NO-independent but transcription- and
      translation-dependent mechanism. Additionally, both agents induce a NO-dependent
      decrease of sGC subunit mRNA. Decreased sGC subunit protein and mRNA levels are
      also observed in adult rat brain after focal injection of IL-1beta or LPS.

PMID- 14597103
TI  - Lack of correlation between the reduction of serum immunoglobulin concentration
      and the CTG repeat expansion in patients with type 1 dystrophia [correction of
      Dystrofia] myotonica.
AB  - The length of the CTG repeat in the 3' untranslated region of the DMPK gene is
      considered to be associated with clinical severity in type 1 Dystrofia Myotonica
      (DM1) and has also been suggested to correlate with the degree of deficiency of
      IgG noted in these patients. Total serum level of IgG and IgG subclasses was
      therefore measured in 61 Swedish patients with DM1, the largest number of
      patients investigated to date in this respect. Almost half (44%) of the DM1
      patients showed a serum concentration of IgG below the normal range. Deficiency
      of IgG1, IgG2 or IgG3 was noted in 26%, 7% and 20% of the patients, respectively.
      As transcription of genes 3' of the DMPK gene on chromosome 19 is reduced in DM1
      patients, a decreased expression of the alpha chain of the receptor involved in
      IgG catabolism, FcRn, may theoretically be responsible for the low serum IgG in
      DM1 patients. No correlation was however found between the number of CTG repeats,
      levels of FcRn transcripts in either muscle tissue or lymphocytes and serum IgG
      levels.

PMID- 14597102
TI  - Langerhans cells beta 2-adrenoceptors: role in migration, cytokine production, Th
      priming and contact hypersensitivity.
AB  - We showed that norepinephrine (NE) hampers IL-12 and stimulates IL-10 production
      via adrenoceptors (ARs) in bone marrow-derived dendritic cells (BMDC) influencing
      their Th priming ability. Others have shown that Langerhans cells (LC) express
      mRNA for beta1-, beta2- and alpha1(A)-(ARs) and that catecholamines may inhibit
      the antigen-presenting capability via beta2-ARs. Here, we show that also BMDC
      express mRNA for beta1-, beta2-, alpha2(A)- and alpha2(C)-ARs. Inhibition of IL
      12 is mediated by both beta2- and alpha2(A)-ARs, while stimulation of IL-10 by
      beta2-ARs only. In addition, LC migration, the contact hypersensitivity response
      (CHS) and production of IFN-gamma and IL-2 in draining lymph node cells is
      increased in mice treated topically with the beta2-AR antagonist ICI 118,551
      during FITC sensitization. Activation of beta2-ARs in BMDC before adoptive
      transfer could reduce both migration and CHS response to FITC. Finally,
      preincubation of BMDC with LPS in presence of the specific beta2-AR agonist
      salbutamol impaired their chemotactic response to CCL19 and CCL21 and this effect
      was neutralized by anti-IL-10 mAb. We suggest that the physiological activation
      of beta2-ARs in DC (LC) results in stimulation of IL-10 which in turn restrains
      DC (LC) migration influencing antigen presentation and the consequent CHS
      response.

PMID- 14597105
TI  - The 'immunological-synapse' at its APC side in relapsing and secondary
      progressive multiple sclerosis: modulation by interferon-beta.
AB  - Reciprocal interactions between T cells and antigen-presenting cells (APCs)
      within the 'Immunological-Synapse' (IS) govern immune cell autoreactivity in
      multiple sclerosis (MS). The present study examined the expression of a range of
      co-stimulatory molecules: CD40, CD54, CD80, CD86 and HLA-DR, on the cell-surface
      of CD14(+) peripheral blood monocytes (PBM) from relapsing-remitting (RR) and
      secondary-progressive (SP)-MS patients, prior to and during 1 year of Interferon
      (IFN)-beta-1a (Rebif(R)) therapy. Prior to treatment, patients from both MS
      subtypes expressed elevated CD80 and reduced CD40 levels in comparison to
      controls. CD86 expression was significantly reduced in SP compared to RR patients
      and controls. IFN-beta therapy led to a significant reduction in the expression
      of CD54 and CD80 in both groups of patients as well as to elevation of CD40 and
      CD86 expression in SP patients. These results confirm IFN-mediated modulation of
      the APC surface within the immunological-synapse and implicate CD80 and CD86 as
      targets for interventional therapies in MS as well as other Th1-mediated
      autoimmune diseases.

PMID- 14597104
TI  - Cross-reactivity between related sequences found in Acinetobacter sp.,
      Pseudomonas aeruginosa, myelin basic protein and myelin oligodendrocyte
      glycoprotein in multiple sclerosis.
AB  - To investigate the possible role of molecular mimicry to bacterial components in
      multiple sclerosis (MS) pathogenesis we examined antibody responses to mimicry
      peptide sequences of Acinetobacter, Pseudomonas aeruginosa and myelin components.
      Antibodies to mimicry peptides from Acinetobacter (p<0.001), P. aeruginosa
      (p<0.001), myelin basic protein (MBP) (p<0.001) and myelin oligodendrocyte
      glycoprotein (MOG) (p<0.001) were significantly elevated in MS patients compared
      to controls. Antisera against MBP (residues 110-124) reacted with both
      Acinetobacter and Pseudomonas peptides from 4- and gamma-carboxymuconolactone
      decarboxylase, respectively. MOG (residues 43-57) antisera reacted with
      Acinetobacter peptide from 3-oxo-adipate-CoA-transferase subunit A. The role of
      these bacteria in MS is unclear but demonstrates that molecular mimicry is not
      restricted to viruses suggesting bacterial infections could play a role in MS
      pathogenesis. Further work is required to evaluate the relevance of these cross
      reactive antibodies to the neuropathology of MS.

PMID- 14597106
TI  - Effect of glatiramer acetate (Copaxone) on CD4+CD25high T regulatory cells and
      their IL-10 production in multiple sclerosis.
AB  - CD4(+)CD25(high) T regulatory (Tr) cells, representing high IL-2 receptor alpha
      chain expressing cells, have been shown to inhibit proliferation and cytokine
      secretion by CD4(+) T cells that are assumed to represent important effector
      cells in auto-aggressive immunity. Tr cells may therefore be considered of
      importance in the pathogenesis of multiple sclerosis (MS). Glatiramer acetate
      (GA; Copaxone) is approved as a disease-modulating agent that ameliorates the
      course of MS. The goal of this study was to examine in vitro effects of GA on Tr
      cells from MS patients subgrouped according to treatment without or with disease
      modulating drugs, and healthy controls (HC). Three-colour flow cytometry was used
      to investigate in vitro influence of GA, and of the encephalitogenic myelin basic
      protein (MBP) peptide 83-89 as control, on the blood Tr cell proportion and on
      their functionally important cell surface molecules CD45RO, CD69, CD95 and HLA
      DR, and on intracellular CTLA-4 and IL-10. Irrespective of exposure to GA or
      MBP((83-99)), levels of blood Tr cells expressing HLA-DR remained low in
      untreated MS patients and HC compared to the three treated MS patient groups. In
      vitro exposure to GA resulted in elevated levels of IL-10 producing Tr cells in
      all MS patient groups irrespective of receiving treatment as well as in HC.
      Exposure to GA or MBP((83-99)) had no effects on levels of Tr cells expressing
      other above-mentioned molecules. We conclude that GA induces elevated IL-10
      production by Tr cells that is uniform and independent of ongoing MS treatment
      with IFN-beta or GA or IFN-beta+GA.

PMID- 14597107
TI  - Neuro-inflammatory risk factors for treatment failure in "early second stage"
      sleeping sickness patients treated with pentamidine.
AB  - In a clinical trial on efficacy of Pentamidine in second stage Trypanosoma brucei
      gambiense patients with </=20 cells/microl in cerebrospinal fluid (CSF), 43% of
      treatment failures were observed. We hypothesised that unsuccessful treatment was
      caused by uncured brain infection. The relationship between treatment outcome and
      CSF cell count, protein concentration, presence of trypanosomes, the intrathecal
      immune response, and CSF total IgM and trypanosome specific antibodies detected
      by LATEX/IgM and LATEX/T.b. gambiense card agglutination tests was examined. Cell
      counts of 11-20 cells/microl, intrathecal IgM synthesis, CSF end-titres in
      LATEX/IgM >/=4 and LATEX/T.b. gambiense positive CSF, were associated with
      treatment failure. Detection of intrathecal IgM synthesis is valuable for
      assessment of brain involvement and treatment decision.

PMID- 14597108
TI  - Intrathecal synthesis of monocyte chemoattractant protein-1 (MCP-1) in
      amyotrophic lateral sclerosis: further evidence for microglial activation in
      neurodegeneration.
AB  - Autopsy studies and animal experiments suggest that microglial inflammation
      contributes to the pathogenesis of amyotrophic lateral sclerosis (ALS). Monocyte
      chemoattractant protein (MCP-1) might play an important role in microglial
      recruitment. We studied MCP-1 levels in sera and cerebrospinal fluid of 29 ALS
      patients and compared the results with 11 control patients with tension headache.
      The MCP-1 level was determined using enzyme-linked immunosorbent assays (ELISA).
      A significant increase in cerebrospinal fluid MCP-1 level but not serum level was
      seen in the patients with ALS compared to the control subjects. These results
      suggest that cerebrospinal fluid MCP-1 activity may be a sensitive marker for
      neuroinflammation in ALS useful for monitoring treatment trials in ALS.

PMID- 14597109
TI  - Association of the Fc gamma receptor IIA-R/R131 genotype with myasthenia gravis
      in Dutch patients.
AB  - Myasthenia gravis (MG) susceptibility is partially determined by allelic
      heterogeneity of immune-modulatory genes. IgG receptors (FcgammaR) link the
      humoral and cellular branches of the immune system, and regulate immune responses
      and inflammation. Three FcgammaR subclasses (FcgammaRIIa, FcgammaRIIIa, and
      FcgammaRIIIb) exhibit functional polymorphisms, which affect efficiency of
      FcgammaR-mediated functions. FcgammaRIIa genotypes, but not FcgammaRIIIa and
      FcgammaRIIIb genotypes, were differentially distributed among 107 MG patients as
      compared to 239 healthy controls (Pz.Lt;0.01), with a relative increase of the
      FcgammaRIIa-R/R131 genotype (Odds ratio 2.4, 95% confidence interval 1.4-3.9).
      These data suggest that the FcgammaRIIa-R/R131 genotype is a marker for
      susceptibility to MG.

PMID- 14597110
TI  - Elucidation of the collision induced dissociation pathways of water and alcohol
      coordinated complexes containing the uranyl cation.
AB  - Multiple-stage tandem mass spectrometry was used to characterize the dissociation
      pathways for complexes composed of (1) the uranyl ion, (2) nitrate or hydroxide,
      and (3) water or alcohol. The complex ions were derived from electrospray
      ionization (ESI) of solutions of uranyl nitrate in H2O or mixtures of H2O and
      alcohol. In general, collisional induced dissociation (CID) of the uranyl
      complexes resulted in elimination of coordinating water and alcohol ligands. For
      undercoordinated complexes containing nitrate and one or two coordinating alcohol
      molecules, the elimination of nitric acid was observed, leaving an ion pair
      composed of the uranyl cation and an alkoxide. For complexes with coordinating
      water molecules, MS(n) led to the generation of either [UO2(2+)OH-] or
      [UO2(2+)NO3(-)]. Subsequent CID of [UO2(2+)OH-] produced UO2(+). The base peak in
      the spectrum generated by the dissociation of [UO2(2+)NO3(-)], however, was an
      H2O adduct to UO2(+). The abundance of the species was greater than expected
      based on previous experimental measurements of the (slow) hydration rate for
      UO2(+) when stored in the ion trap. To account for the production of the hydrated
      product, a reductive elimination reaction involving reactive collisions with
      water in the ion trap is proposed.

PMID- 14597111
TI  - Evaluation of alkali and alkaline earth metal cation selectivities of lariat
      ether amides by electrospray ionization mass spectrometry.
AB  - Lariat ethers with pendant amide groups have shown promise as new ion sensors
      because of their selectivity towards particular metal ions. In this study we
      report alkali and alkaline earth metal binding selectivities of dibenzo-16-crown
      5 and fifteen dibenzo-16-crown-5 lariat ether amides (LEAs) as determined by
      electrospray ionization mass spectrometry (ESI-MS). Additionally, the influence
      of the acid/base nature of the solution on metal cation selectivity is
      investigated. The validity of using ESI-MS for determination of selectivities is
      established by analogous experiments using hosts with known binding constants for
      the same metal cations and solvent systems. Collisionally activated dissociation
      (CAD) is used to evaluate the influence of the alkali metal cation binding on the
      fragmentation of the LEAs.

PMID- 14597112
TI  - Suppression of the lower charge state ions in the external accumulation RF
      multipole with a reduced trapping DC potential.
AB  - Radio frequency (RF) multipoles are increasingly used in mass spectrometry as two
      dimensional ion traps for ion accumulation and preselection. It was reported
      recently that ions having lower charge states, in particular singly charged ions,
      can be efficiently removed from such an ion trap when reduced DC trapping
      voltages are applied. This procedure can be useful for removing singly charged
      species contributing chemical noise to mass spectra of complex biomolecular
      samples, e.g., solvent contaminants in LC-MS or relatively low MW ampholytes in
      CIEF-MS experiments. We consider a physical mechanism and derive relationships
      that provide a quantitative description for the low charge state ejection
      phenomenon. Experimental conditions for the efficient discrimination against
      lower charge states are evaluated. Initial experimental observations reported are
      in agreement with the theoretical treatment.

PMID- 14597113
TI  - Particle discriminator interface for nanoflow ESI-MS.
AB  - An atmosphere to vacuum interface was designed to exploit the different mobility
      and momentum characteristics of ions, and charged and neutral particles in
      electrospray ionization-mass spectrometry. The purpose of this device is to
      transmit with high efficiency the ions created at atmospheric pressure into the
      mass analyzer and to deflect the large charged and neutral particles prior to
      entrance into the vacuum system, thereby maintaining system cleanliness and
      stability. This interface is particularly suitable for low flow rate electrospray
      ionization-mass spectrometry where the close proximity of the electrospray
      emitters to the vacuum entrance, and near total consumption of the entire spray,
      leads to the production of large quantities of non-desolvated droplets and large
      charged and neutral particles. The improvement involves the application of
      potential gradients to a particle discriminator space located between the gas
      restricting ion entrance orifice of the mass spectrometer and the exit of a
      heated laminar flow chamber to divert large particles from the gas conductance
      limiting orifice. A counter-current flow of drying gas is used to deflect neutral
      particles and solvent vapor. Two stages of desolvation are achieved with the
      combined effects of the curtain gas and heated laminar flow chamber. This
      enhances the efficiency of desolvation and ion production, and stabilizes the
      resulting ion current under a wide variety of solvent compositions. In addition,
      this system eliminates the problems associated with the boiling of solution in
      nanospray tips when operated in close proximity to a heated mass spectrometer
      inlet. The particle discriminator interface gives approximately a 2-fold
      improvement in ion count rates, and a 3-fold improvement in stability (as
      measured by the signal relative standard deviation).

PMID- 14597114
TI  - Identification of diethylene glycol monobutyl ether as a source of contamination
      in an ion trap mass spectrometer.
AB  - Tandem liquid chromatography-mass spectrometry coupled to online radioactive
      material detection (LC/RAM/MS/MS) is a technique that is used routinely for in
      vivo and in vitro drug metabolism studies and allows for a simultaneous
      correlation between radiochemical peaks and mass spectral data. The compound
      diethylene glycol monobutyl ether (DGBE), a component of a commercially available
      scintillation cocktail for RAM analysis, was identified as a source of
      overwhelming chemical noise in a mass spectrometer which was used in an
      LC/RAM/MS/MS configuration. In this report, we describe the identification of
      DGBE as the source of the chemical noise and the methods that were used to
      minimize the exposure of the mass spectrometer to volatile components of the
      scintillation cocktail.

PMID- 14597115
TI  - Detection and characterization by mass spectrometry of radical adducts produced
      by linoleic acid oxidation.
AB  - The formation of linoleic acid radical species under the oxidative conditions of
      the Fenton reaction (using hydrogen peroxide and Fe (II)) was monitored by FAB-MS
      and ES-MS using the spin trap 5,5-dimethyl-1-pyrrolidine-N-oxide, DMPO. Both the
      FAB and ES mass spectra were very similar and showed the presence of ions
      corresponding to carbon- and oxygen centered spin adducts (DMPO/L*, DMPO/LO*, and
      DMPO/LOO*). Cyclic structures, formed between the DMPO oxygen and the neighboring
      carbon of the fatty acid, were also observed. Electrospray tandem mass
      spectrometry of these ions was performed to confirm the proposed structure of
      these adducts. All MS/MS spectra showed an ion at m/z 114, correspondent to the
      [DMPO + H]+, and a fragment ion due to loss of DMPO (loss of 113 Da), confirming
      that they are DMPO adducts. ES-MS/MS spectra of alkoxyl radical adducts
      (DMPO/LO*) showed an additional ion at m/z 130 [DMPO - O + H]+, while ES MS/MS of
      peroxyl radical adducts (DMPO/LOO*) showed a fragment ion at m/z 146 [DMPO - OO +
      H]+, confirming both structures. Other fragment ions were observed, such as alkyl
      acylium radical ions, formed by cleavage of the alkyl chain after loss of water
      and the DMPO molecule. The identification of fragment ions observed in the MS/MS
      spectra of the different DMPO adducts suggests the occurrence of structural
      isomers containing the DMPO moiety both at C9 and C13. The use of ES tandem mass
      spectrometry, associated with spin trapping experiments, has been shown to be a
      valuable tool for the structural characterization of carbon and oxygen-centered
      spin adducts of lipid radicals.

PMID- 14597116
TI  - Electrospray tandem mass spectrometric investigations of morphinans.
AB  - In this study positive ESI tandem mass spectra of the [M + H]+ ions of morphinan
      alkaloids obtained using an ion trap MS were compared with those from a triple
      quadrupole MS. This allows to assess the differences of the tandem-in-time versus
      the tandem-in-space principle, often hampering the development of ESI MS/MS
      libraries. Fragmentation pathways and possible fragment ion structures were
      discussed. In order to obtain elemental composition, accurate mass measurements
      were performed. According to the MS/MS fragmentation pathway, the investigated
      compounds can be grouped into 4 subsets: (1) morphine and codeine, (2)
      morphinone, codeinone, and neopinone, (3) thebaine and oripavine, (4)
      salutaridine and salutaridinol. Salutaridinol-7-O-acetate shows a different
      fragmentation behavior because of the favored loss of acetic acid. Although most
      fragment ions occur in both ion trap and triple quad tandem mass spectra, some
      are exclusively seen in either type. For triple quad, quadrupole time-of-flight
      and FT-ICR MS/MS, the base peak of morphine results from an ion at m/z 165 that
      contains neither nitrogen nor oxygen. This ion is not found in ion trap MS/MS,
      but in subsequential MS3 and MS4.

PMID- 14597117
TI  - Tandem mass spectrometric strategies for determination of sulfation positions and
      uronic acid epimerization in chondroitin sulfate oligosaccharides.
AB  - Chondroitin sulfate (CS) is a glycosaminoglycan consisting of repeating (HexA
      GalNAc sulfate) disaccharides, the functions of which depend on patterns of
      sulfation and uronic acid epimerization. The correlation of biological activities
      with structure requires a strategy to determine the sequences of CS
      oligosaccharides without the need for total isolation. Tandem mass spectrometry
      has enabled the development of proteomics, based on CID fragmentation of ions
      produced from complex mixtures of proteolytic peptides, and has the potential for
      rapid sequencing of CS and other glycosaminoglycan classes. The most challenging
      aspects of CS sequencing are to distinguish GalNAc residues sulfated at the 4-
      versus the 6-position and uronic acid epimers. This work describes the utility of
      (1) reducing terminal derivatives and (2) control of precursor ion charge state
      for tandem mass spectrometric strategies for determining GalNAc sulfation
      positional isomers of CS. The capability of tandem MS to differentiate uronic
      acid epimers is also shown, providing evidence that complete or nearly complete
      information on CS covalent structure may be obtained using tandem MS.

PMID- 14597118
TI  - Determination of the activation energy for unimolecular dissociation of a non
      covalent gas-phase peptide: substrate complex by infrared multiphoton
      dissociation fourier transform ion cyclotron resonance mass spectrometry.
AB  - The activation energy for the unimolecular dissociation of a non-covalent
      supramolecular complex between an Artificial Cationic Receptor A ([Gua-Val-Val
      Val-Amide]+, in which Gua is guanidiniocarbonyl pyrrole) and an Anionic
      Tetrapeptide B ([N-Acetyl-Val-Val-Ile-Ala]-) has been determined by measurement
      of the dissociation rate constant as a function of infrared CO2 laser power
      density. Singly-charged quasimolecular [A + B + H]+ ions are isolated, stored in
      a Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer, and
      irradiated by IR photons. The rate constant for dissociation of the non-covalent
      complex is determined at five different laser power densities. A plot of the
      natural logarithm of the first-order rate constant versus the natural logarithm
      of the laser power density yields a straight line, the slope of which provides an
      approximate measure of the activation energy (Ea(laser)) for dissociation.
      Ea(laser) is calculated by a relationship derived earlier by Dunbar and with a
      newly proposed equation by Paech et al. The results of the two approaches deliver
      significantly different activation energy values for the unimolecular
      dissociation of the non-covalent complex. We obtain EaI(laser) = 0.67 eV (Dunbar
      approximation) and EaII(laser) = 1.12 eV (Paech et al. approximation).
      Differences between the two approaches are discussed with respect to non-covalent
      complexes.

PMID- 14597119
TI  - Matrix effect in bio-analysis of illicit drugs with LC-MS/MS: influence of
      ionization type, sample preparation, and biofluid.
AB  - The purpose of the present work was to evaluate the synergistic effect of
      ionization type, sample preparation technique, and bio-fluid on the presence of
      matrix effect in quantitative liquid chromatography (LC)-MS/MS analysis of
      illicit drugs by post-column infusion experiments with morphine (10-microg/mL
      solution). Three bio-fluids (urine, oral fluid, and plasma) were pretreated with
      four sample preparation procedures [direct injection, dilution, protein
      precipitation, solid-phase extraction (SPE)] and analyzed by both LC-electrospray
      ionization (ESI)-MS/MS and LC-atmospheric pressure chemical ionization (APCI)
      MS/MS. Our results indicated that both ionization types showed matrix effect, but
      ESI was more susceptible than APCI. Sample preparation could reduce (clean up) or
      magnify (pre-concentrate) matrix effect. Residual matrix components were specific
      to each bio-fluid and interfered at different time points in the chromatogram. We
      evaluated matrix effect in an early stage of method development and combined
      optimal ionization type and sample preparation technique for each bio-fluid.
      Simple dilution of urine was sufficient to allow for the analysis of the analytes
      of interest by LC-APCI-MS/MS. Acetonitrile protein precipitation provided both
      sample clean up and concentration for oral fluid analysis, while SPE was
      necessary for extensive clean up of plasma prior to LC-APCI-MS/MS.

PMID- 14597120
TI  - Weighted two-band target entropy minimization for the reconstruction of pure
      component mass spectra: simulation studies and the application to real systems.
AB  - A method is proposed, on the basis of a recently developed algorithm--Band Target
      Entropy Minimization (BTEM)--to reconstruct mass spectra of pure components from
      mixture spectra. This method is particular useful in dealing with spectral data
      with discrete features (like mass spectra). Compared to the original BTEM, which
      has been applied to differentiable spectroscopies such as Fourier-transfer
      infrared spectroscopy (FTIR), ultraviolet (UV), Raman, and nuclear magnetic
      resonance (NMR), the latest modifications were obtained through: (1)
      Reformulating the objective function using the peak heights instead of their
      derivatives; (2) weighting the abstract vector VT to reduce the effect of noise;
      (3) using a two-peak targeting strategy (tBTEM) to deal with strongly overlapping
      peaks; and (4) using exhaustive search to locate all the component spectra. A set
      of 50 multi-component mass spectra was generated from ten reference experimental
      pure component spectra. Many of the compounds chosen have common MS fragments and
      therefore, many of the pure component spectra have considerable intensity in same
      data channels. In addition, a set of MS spectra from a real system with four
      components was used to examine the newly developed algorithm. Successful
      reconstruction of the ten component spectra of the simulated system and the four
      component spectra of the real system was rapidly achieved using the new tBTEM
      algorithm. The advantages of the new algorithm and its implication for rapid
      system identification of unknown mixtures are readily apparent.

PMID- 14597122
TI  - Factors influencing the analytical performance of an atmospheric sampling glow
      discharge ionization source as revealed via ionization dynamics modeling.
AB  - A kinetic model is developed for the dynamic events occurring within an
      atmospheric sampling glow discharge that affect its performance as an ion source
      for analytical mass spectrometry. The differential equations incorporate
      secondary electron generation and thermalization, reagent and analyte ion
      formation via electron capture and ion-molecule reactions, ion loss via
      recombination processes, diffusion, and ion-molecule reactions with matrix
      components, and the sampling and pumping parameters of the source. Because the
      ion source has a flow-through configuration, the number densities of selected
      species can be estimated by applying the steady-state assumption. However,
      understanding of its operation is aided by knowledge of the dynamic behavior, so
      numerical methods are applied to examine the time dependence of those species as
      well. As in other plasma ionization sources, the ionization efficiency is
      essentially determined by the ratio of the relevant ion formation and
      recombination rates. Although thermal electron and positive reagent ion number
      densities are comparable, the electron capture/ion-molecule reaction rate
      coefficient ratio is normally quite large and the ion-electron recombination rate
      coefficient is about an order of magnitude greater than that for ion-ion
      recombination. Consequently, the efficiency for negative analyte ion formation
      via electron capture is generally superior to that for positive analyte ion
      generation via ion-molecule reaction. However, the efficiency for positive
      analyte ion formation should be equal to or better than that for negative analyte
      ions when both ionization processes occur via ion-molecule reaction processes
      (with comparable rate coefficients), since the negative reagent ion density is
      considerably less than that for positive reagent ions. Furthermore, the
      particularly high number densities of thermal electrons and reagent ions leads to
      a large dynamic range of linear response for the source. Simulation results also
      suggest that analyte ion number densities might be enhanced by modification of
      the standard physical and operating parameters of the source.

PMID- 14597121
TI  - Use of double-depleted 13C and 15N culture media for analysis of whole cell
      bacteria by MALDI time-of-flight and Fourier transform mass spectrometry.
AB  - In the present paper, results demonstrating the significant advantages of matrix
      assisted laser desorption/ionization (MALDI) analysis of whole cell samples of
      bacteria grown on double isotopically-depleted (13C and 15N) media are presented.
      It is shown that several advantages accrue for MALDI with a 9.4 T Fourier
      transform mass spectrometer (FTMS). Of particular note, for analysis of whole
      cells, sample preparation is simple and chemical interference is reduced.
      Moreover, ion coalescence problems are minimized, and data-base identification of
      proteins facilitated. Furthermore, high resolution mass spectra obtained from
      such whole cells show significant improvement in apparent mass resolving power
      and mass measurement accuracy, whether time-of-flight or FTMS MALDI is used. As a
      consequence, it becomes possible to detect subtle details in the chemistry of the
      organism, such as the presence of both post-translationally modified and
      unmodified versions of the same proteins. This approach is also adaptable to
      direct assay of over-expressed proteins from Escherichia coli cultures and should
      facilitate studies aimed at the detection of medically important cellular
      biomarker proteins.

PMID- 14597125
TI  - Potentiation of trichothecene-induced leukocyte cytotoxicity and apoptosis by TNF
      alpha and Fas activation.
AB  - Trichothecene mycotoxins cause immunosuppression by inducing apoptosis in
      lymphoid tissue. Trichothecene-induced leukocyte apoptosis can be augmented by
      bacterial lipopolysaccharide (LPS) but the mechanisms involved in this
      potentiating effect are not completely understood. The objective of this study
      was to test the hypothesis that the trichothecene deoxynivalenol (DON, vomitoxin)
      can interact with LPS directly and other mediators or agonists associated with
      immune/inflammatory responses to induce apoptosis in primary murine leukocyte
      cultures. Primary leukocyte suspensions were prepared from murine thymus (TH),
      spleen (SP), bone marrow (BM) and Peyer's patches (PP) and then cultured with DON
      in the absence or presence of LPS, prostaglandin E2 (PGE2), anti-immunoglobulin
      (as antigen mimic), dexamethasone, Fas ligand, or TNF-alpha. Cytotoxicity and
      apoptosis were evaluated by MTT assay and morphologic assays, respectively. DON
      was found to inhibit LPS-induced proliferation and dexamethasone-induced
      apoptosis in SP cultures. In contrast, potentiation of DON-induced apoptosis and
      cytotoxicity was observed in BM cultures treated with anti-Fas and in TH cultures
      treated with TNF-alpha. When potentiation of DON-induced apoptosis by TNF-alpha
      was assessed using pharmacological inhibitors, generation of ROS, intracellular
      Ca2+, p38/SAPK, and caspase-3 activation were found to play roles. Taken
      together, these data demonstrate that LPS and its downstream mediators can
      interact with trichothecenes to modulate proliferative, cytotoxic and apoptotic
      outcomes in leukocytes in a tissue-specific manner.

PMID- 14597126
TI  - The toxicity of opiates and their metabolites in HepG2 cells.
AB  - The toxicity of codeine (C), codeinone (CO), morphine (M), oxycodone (OC),
      pholcodine (P) and pholcodine-N-oxide (P-NOX) was assessed in HepG2 cells by
      determining cell viability via the measurement of lactate dehydrogenase (LDH)
      leakage through the membrane, depletion of reduced glutathione (GSH) and
      measurement of total protein content. Incubation of C, M, OC, P or P-NOX with
      HepG2 cells resulted in no significant loss of cell viability, depletion of GSH
      or decreased total protein content. In contrast, with CO there was a marked
      depletion of GSH with significant differences from control cells (P<0.05) being
      detected after as little as 5 min. This effect preceded the loss of cell
      viability and the decrease in total protein content. To identify the cause of GSH
      depletion during incubations with CO, the incubation solutions were analysed by
      liquid chromatography/tandem mass spectrometry (LC/MS/MS). Analysis showed that a
      codeinone-glutathione conjugate (CO-SG) had been formed. This adduct was
      synthesised and characterised by LC/MS/MS and by nuclear magnetic resonance
      spectroscopy (NMR). CO-SG was quantified in the incubation solutions using the
      synthesised standard substance. Results obtained in this study support the
      hypothesis that the toxicity of CO may be partly due to GSH depletion. The
      absence of LDH leakage and GSH depletion in the incubations containing C or OC
      suggests, that the presence of both a double bond at Delta 7 and an adjoining
      keto-group in the 6-position are necessary to elicit the toxicity of M analogues
      with regard to GSH depletion.

PMID- 14597127
TI  - Fumonisin B1-induced apoptosis is associated with delayed inhibition of protein
      kinase C, nuclear factor-kappaB and tumor necrosis factor alpha in LLC-PK1 cells.
AB  - Fumonisin B1 (FB1), the most potent of the fumonisin mycotoxins, is a carcinogen
      and causes a wide range of species-specific toxicoses. FB1 modulates the activity
      of protein kinase C (PKC), a family of phospholipid-dependent serine/threonine
      kinases that play important role in modulating a variety of biologic responses
      ranging from regulation of cell growth to cell death. Although it has been
      demonstrated that FB1 induces apoptosis in many cell lines, the precise mechanism
      of apoptosis is not fully understood. In this study, we investigated the membrane
      localization of various PKC isoforms, PKC enzyme activity, and its downstream
      targets, namely nuclear factor-kappa B (NF-kappaB), tumor necrosis factor alpha
      (TNFalpha), and caspase 3, in porcine renal epithelial (LLC-PK1) cells. FB1
      repressed cytosol to membrane translocation of PKC-alpha, -delta, -epsilon, and 
      zeta isoforms over 24-72 h. The FB1-induced membrane PKC repression was
      corroborated by a concentration-dependent decrease in total PKC activity.
      Exposure of cells to phorbol 12-myristate 13-acetate (PMA) for this duration also
      resulted in repressed PKC membrane localization and activity comparable to FB1.
      Exposure of cells to FB1 (10 microM) was associated with inhibition of cytosol to
      nuclear translocation of NF-kappaB and NF-kappaB-DNA binding at 72 h. The
      expression of TNFalpha was significantly inhibited at 24 and 48 h in response to
      1 and 10 microM FB1. Increased caspase 3 activity was observed in LLC-PK1 cells
      exposed to > or =1 microM FB1 at 48 h. PMA also increased the caspase 3 activity
      at 24 and 48 h. Results suggest that FB1-induced apoptosis involves the
      activation of caspase 3, which is associated with the repression of PKC and
      possibly its down-stream effectors, NF-kappaB and TNFalpha.

PMID- 14597128
TI  - Ozone exposure alters 5-hydroxy-indole-acetic acid contents in dialysates from
      dorsal raphe and medial preoptic area in freely moving rats. Relationships with
      simultaneous sleep disturbances.
AB  - Ozone (O3) has been reported to affect sleep patterns and also striatal and
      mesencephalic contents of 5-hydroxy-indole-acetic acid (5-HIAA) in rats. The aim
      of this work was to elucidate the effects of O3 exposure in rats upon
      extracellular 5-HIAA levels in the dorsal raphe (DR) and the hypothalamic medial
      preoptic area (MPO), two structures involved in sleep-wake homeostasis. Exposure
      to O3 followed a bell-shaped diurnal pattern, similar to that observed in cities
      with high air pollution levels. The highest O3 concentration employed was 0.5
      ppm. Simultaneous polygraphic records were performed to evaluate the concomitant
      effects of this exposure model on sleep patterns. Results showed that
      extracellular 5-HIAA levels increased by 28% in the DR (P=0.0213) while
      paradoxical sleep (PS) decreased by 56% (P=0.0000) during the light O3 exposure
      phase. A decrease of 32% in 5-HIAA levels in the MPO (P=0.0450), and of 22% in
      slow wave sleep (SWS) (P=0.0002) and an increase of 21% in wakefulness (P=0.0430)
      during the dark post-exposure (Dpost) phase were also observed. We propose that
      the decrease in PS is the behavioral expression of disruptions of serotonergic DR
      modulation and, that post-exposure effects observed in the MPO can be explained
      on the basis of the hypothalamic role in the sleep-wake cycle.

PMID- 14597129
TI  - Critical role of histidine residues in cyclohexanone monooxygenase expression,
      cofactor binding and catalysis.
AB  - Cyclohexanone monooxygenase (CMO) is a member of the flavin monooxygenase
      superfamily of enzymes that catalyze both nucleophilic and electrophilic
      reactions involving a common C4a hydroperoxide intermediate. To begin to probe
      structure-function relationships for these enzymes, we investigated the roles of
      histidine residues in CMO derived from Acinetobacter NCIB 9871, with particular
      emphasis on the wholly conserved residue, His163 (H163). CMO activity was readily
      inactivated by diethyl pyrocarbonate (DEPC), a selective chemical modifier of
      histidine residues. Each of the seven histidines in CMO was then individually
      mutated to glutamine and the mutants expressed and purified from Escherichia
      coli. Only the H59Q mutant failed to express at significant levels. The H96Q
      enzyme was found to have a greatly reduced flavin adenine dinucleotide (FAD)
      content, indicative of compromised cofactor retention. The only significant
      effect on kcat occurred with the H163Q mutant, which exhibited an approximately
      10-fold lower turnover of the prototypical substrate, cyclohexanone. This was
      accompanied by a doubling in the Km [NADPH] compared to the wild-type enzyme,
      suggesting that the functional decrement in H163Q is probably not solely a
      reflection of impaired NADPH binding. These data establish a critical role for
      H163 in CMO catalysis and prompt the hypothesis that this conserved residue plays
      a similarly important functional role across the flavin monooxygenase family of
      enzymes.

PMID- 14597131
TI  - Comparative action of 1,4-phenylenebis(methylene)selenocyanate and its
      metabolites against 7,12-dimethylbenz[a]anthracene-DNA adduct formation in the
      rat and cell proliferation in rat mammary tumor cells.
AB  - 1,4-phenylenebis(methylene)selenocyanate (p-XSC) inhibits 7,12
      dimethylbenz[a]anthracene (DMBA)-induced mammary carcinogenesis and DMBA-DNA
      binding in the rat mammary gland. Tetraselenocyclophane (TSC) was identified in
      rat feces as a metabolite of p-XSC. This led us to postulate the metabolic
      pathway: p-XSC-->glutathione conjugate (p-XSeSG)-->aromatic selenol (p-XSeH)-
      >TSC. Whether p-XSC or one of its metabolites is responsible for cancer
      prevention is the focus of this study. We utilized the DMBA-DNA binding assay
      with p-XSC as a positive control to evaluate the chemopreventive potential of p
      XSC metabolites at dietary selenium levels of 10 ppm. Rats were fed AIN-76A diet
      supplemented with various selenium compounds for 1 week prior to the oral
      administration of a single dose of [3H]DMBA (5 mg per rat, specific activity 51.3
      mCi/mmol). The rats were sacrificed 24 h later and DNA was isolated from the
      mammary fat pads. Relative levels of total binding were: [pmol/mg DNA, mean +/-
      S.D., n=6]; DMBA [7.2 +/- 1.6]; DMBA+p-XSC [3.5 +/- 2.7]; DMBA+p-XSeSG [2.2 +/-
      1.1]; DMBA+TSC [5.6 +/- 2.9]. All selenium compounds, except TSC, significantly
      inhibited DMBA-DNA adduct formation; however, the difference between p-XSC and p
      XSeSG was not statistically significant. The inhibition of total binding was
      attributed to a reduction in the formation of the three major adducts derived
      from bay-region diol epoxides of DMBA. On the basis of their chromatographic
      characteristics, these were identified as anti-diol-epoxide:deoxyguanosine, syn
      diol-epoxide:deoxyadenosine, and anti-diol-epoxide:deoxyadenosine. Our results
      suggest that p-XSeSG, but not TSC, is the likely inhibitor of mammary cancer.
      Selenium levels measured by atomic absorption spectroscopy in the target organ
      (mammary fat pads) and in plasma following the dietary administration of selenium
      compounds were in the order of p-XSeSG congruent with p-XSC>TSC. These results
      appear to be consistent with their order of inhibitory effects on total DMBA-DNA
      binding. Further in vitro studies of the effect of selenium compounds on cell
      proliferation suggest that, depending on the dose and time point selected, p-XSC
      is comparable to or better than p-XSeSG; but both are more effective than TSC.
      Collectively, our in vivo and in vitro results indicate that p-XSC and its
      conjugate are better candidates than TSC for future studies on mammary cancer
      chemoprevention.

PMID- 14597130
TI  - Radiosensitizing properties of novel hydroxydicarboxylatoplatinum(II) complexes
      with high or low reactivity with thiols: two modes of action.
AB  - We examined radiosensitizing properties of two novel platinum complexes
      (ethylenediamine(L-malato)platinum(II)), Pt1 and bis(1-ethylimidazole(L
      malato)platinum(II)), Pt4. Initial double strand break (DSB) level and DSB
      rejoining were measured, using pulse field gel electrophoresis (PFGE) in human G1
      phase lymphocytes subjected to Pt complex treatment alone and in combination with
      10Gy of X-rays. Effects of Pt complex pre-treatment followed by X-irradiation
      were examined on survival (clonogenic ability) and growth (48 h growth tests) in
      Chinese hamster ovary (CHO-K1), xrs6 and L5178Y (LY) cells (LY-R and LY-S
      sublines). Cell cycle distributions of CHO cells after drug treatment were
      determined with the use of flow cytometry. Pt1 slowed down rejoining of X-ray
      induced DSB. It exerted a more than additive lethal effect on CHO-K1 cells but
      not on L5178Y cells subjected to combined Pt complex treatment and X-irradiation.
      In xrs6 cells the effect of combined Pt1+X treatment was additive. We conclude
      that, as earlier proposed for other Pt complexes, the radiosensitizing effect of
      Pt1 is connected with converting repairable DNA damage into irrepairable one
      (mode (i) of action). The requirements for this mode of sensitization are
      functional DNA repair systems (nucleotide excision repair (NER) and non
      homologous end-joining (NHEJ)). Pt4 does not slow down DSB rejoining. It shows a
      considerable ability to arrest cells in G2 phase. We assume that Pt4 pre
      treatment arrests cells in G2 phase and thus sensitizes to X-rays these cells
      that have a radiosensitive G2 phase (mode (ii) of action).

PMID- 14597132
TI  - Effect of halothane on lung carcinoma cells A 549.
AB  - The halogenated hydrocarbons, such as halothane, are widely used as anesthetics
      in clinical practice; however their application is often accompanied with
      metabolic, cardiovascular and respiratory complications. One of the possible
      factors for this negative outcome might be the severe toxicity of these agents.
      In this paper, we investigate in vitro effects of halothane on human lung
      carcinoma A 549 cells, namely on their cytotoxicity, adhesive properties and
      metabolic activity. The cytotoxicity response of lung carcinoma A 549 cells to
      halothane was determined by lactate dehydrogenase (LDH) assay (for cytotoxicity),
      by detachment assay after adhesion to type IV collagen (for cell adhesive
      properties) and by surface tension measurements of culture medium (for cell
      metabolic activity). Regarding the cytotoxicity, the determined maximal non-toxic
      concentration of halothane on A 549 cells, given here as volume percentages
      (vol.%) was 0.7 vol.% expressed as aqueous concentration in the culture medium.
      Direct measurement of the actual halothane concentration in the culture medium
      showed that 0.7 vol.% corresponds to 1.05 mM and 5.25 aqueous-phase minimum
      alveolar concentration (MAC). Concentrations equal or higher than 1.4 vol.% (2.1
      mM; 10.5 MAC) of halothane provoked complete detachment (cell death), or
      reduction of initial adhesion to collagen IV in half of the cell population.
      Surfactant production of A 549 cells, registered up to 48 h after halothane
      treatment, was inhibited by halothane concentrations as low as 0.6 vol.% (0.9 mM;
      4.5 MAC). Our results demonstrate that sub toxic halothane concentrations of 0.6
      vol.% inhibits surfactant production; concentrations in the range 0.8-1.4 vol.%
      induce membrane damages and concentrations equal and higher than 1.4 vol.%--cell
      death of approximately 50% of the cells.

PMID- 14597133
TI  - Protective effect of low molecular weight heparin on oxidative injury and
      cellular abnormalities in adriamycin-induced cardiac and hepatic toxicity.
AB  - The aim of the present work is to evaluate the effect of a heparin derivative,
      low molecular weight heparin (LMWH) on the biochemical changes, tissue
      peroxidative damage and abnormal antioxidant levels in adriamycin (ADR) induced
      cardiac and hepatic toxicity. Male Wistar rats (140 +/- 10 g) were divided into
      four groups: untreated control (group I), ADR group (a single dose intravenous
      injection of 7.5 mg/kg ADR--group II), LMWH control (300 microg/day per rat s.c.
      for 1 week--group III) and ADR plus LMWH group (7.5 mg/kg ADR on day 1 of study
      period followed by LMWH treatment, 300 microg/day per rat commencing on day 8 and
      continued for a week. At the end of the 2-week experimental period, all animals
      were terminated. Cellular damage was assessed in terms of serum and tissue
      lactate dehydrogenase (LDH), aminotransferases and alkaline phosphatase (ALP)
      activities. Creatine phosphokinase (CPK) was assessed in the serum and heart
      tissue. The role of LMWH in altering the oxidative stress in ADR-induced toxicity
      was evaluated on the basis of its influence on cardiac and hepatic lipid
      peroxidation and antioxidant status (enzymatic and non-enzymatic)--superoxide
      dismutase (SOD), catalase and glutathione peroxidase (GPx), reduced glutathione
      (GSH), alpha-tocopherol (Vitamin E) and ascorbate (Vitamin C). LMWH
      administration to ADR-induced rats prevented the rise in serum and tissue levels
      of LDH, aminotransferases and ALP, while these parameters were significantly
      elevated in the ADR group in comparison with the control group. Cardiotoxicity
      indicated by rise in serum CPK in the ADR group was attenuated by LMWH treatment
      in group IV. LMWH decreased the cardiac and hepatic lipid peroxidation induced by
      ADR. Histologic examination revealed that the ADR-induced deleterious changes in
      the heart and liver tissues were offset by LMWH treatment. Restoration of
      cellular normalcy accredits LMWH with cytoprotective role in adriamycin-induced
      cardiac and hepatic toxicity.

PMID- 14597135
TI  - Understanding endocytic pathways and intracellular trafficking: a prerequisite
      for effective design of advanced drug delivery systems.

PMID- 14597136
TI  - Actin microfilaments et al.--the many components, effectors and regulators of
      epithelial cell endocytosis.
AB  - The aim of this review is to introduce the advances made over the past several
      years regarding the participation of actin and actin-associated proteins in
      clathrin-mediated endocytosis in simple cell models, and then to consider the
      evidence for the involvement of these effectors in apical clathrin-mediated
      endocytosis in epithelial cells. Basic mechanisms of clathrin-mediated
      endocytosis are initially addressed, followed by a detailed description of the
      actin cytoskeleton: its organization, function and, most importantly, the
      essential role played by proteins and signaling pathways responsible for the
      regulation of actin filament dynamics. Our focus then shifts to the GTPase,
      dynamin and its pivotal role as a bridge between various components of the
      clathrin endocytic machinery and the actin cytoskeleton. Mechanisms and effectors
      of dynamin-dependent endocytosis are then described, with a particular emphasis
      on novel proteins, which link dynamin to actin filaments. We consider additional
      effectors proposed to interact with actin to facilitate clathrin-mediated
      endocytosis in a dynamin-independent manner. The multiple roles which actin
      filaments are thought to play in endocytosis are addressed followed by a more
      detailed characterization of actin filament participation specifically in apical
      endocytosis. We conclude by discussing how these concepts may be integrated to
      improve drug internalization at the apical plasma membrane of epithelial cells.

PMID- 14597137
TI  - Roles of the cytoskeleton and motor proteins in endocytic sorting.
AB  - After internalization, endocytic material is actively transported through the
      cytoplasm, predominantly by microtubule motor proteins. Microtubule-based
      endocytic transport facilitates sorting of endocytic contents, vesicle fusion and
      fission, delivery to lysosomes, cytosolic dispersal, as well as nuclear uptake
      and cytosolic egress of pathogens. Endosomes, like most organelles, move
      bidirectionally through the cytosol and regulate their cellular location by
      controlling the activity of motor proteins, and potentially by controlling
      microtubule and actin polymerization. Control of motor protein activity is
      manifest by increased microtubule "run lengths", and the binding of motor
      proteins to organelles can be regulated by motor protein receptors. A mechanistic
      understanding of how organelles control motor protein activity to allow for
      endocytic sorting presents an exciting avenue for future research.

PMID- 14597138
TI  - Sorting motifs in receptor trafficking.
AB  - A variety of receptors have been analyzed in sufficient detail to identify
      sorting motifs. Initial studies focused on the identification of sequences in the
      cytoplasmic tails of the LDL and transferrin receptors that mediated their
      internalization. These motifs have since been found in the cytoplasmic domains of
      a wide variety of receptors and provide for numerous sorting functions. This
      review will outline the early studies on LDL and transferrin receptors and will
      then focus on two classes of signaling receptors, receptor tyrosine kinases (EGF
      and the insulin receptors) and heterotrimeric G-protein coupled receptors (beta2
      adrenergic receptors). The identification of sorting motifs and proteins that
      bind these motifs will be discussed. Importantly, the studies identify a variety
      of potential targets for modulating the sorting and hence activity of these
      medically important receptors.

PMID- 14597139
TI  - Rab proteins and endocytic trafficking: potential targets for therapeutic
      intervention.
AB  - Rab GTPases serve as master regulators of vesicular membrane transport on both
      the exo- and endocytic pathways. In their active forms, rab proteins serve in
      cargo selection and as scaffolds for the sequential assembly of effectors
      requisite for vesicle budding, cytoskeletal transport, and target membrane
      fusion. Rab protein function is in turn tightly regulated at the level of protein
      expression, localization, membrane association, and activation. Alterations in
      the rab GTPases and associated regulatory proteins or effectors have increasingly
      been implicated in causing human disease. Some diseases such as those resulting
      in bleeding and pigmentation disorders (Griscelli syndrome), mental retardation,
      neuropathy (Charcot-Marie-Tooth), kidney disease (tuberous sclerosis), and
      blindness (choroideremia) arise from direct loss of function mutations of rab
      GTPases or associated regulatory molecules. In contrast, in a number of cancers
      (prostate, liver, breast) as well as vascular, lung, and thyroid diseases, the
      overexpression of select rab GTPases have been tightly correlated with disease
      pathogenesis. Unique therapeutic opportunities lie ahead in developing strategies
      that target rab proteins and modulate the endocytic pathway.

PMID- 14597140
TI  - Mechanisms of TfR-mediated transcytosis and sorting in epithelial cells and
      applications toward drug delivery.
AB  - Transferrin receptor has been an important protein for many of the advances made
      in understanding the intricacies of the intramolecular sorting pathways of
      endocytosed molecules. The unique internalization and recycling functions of
      transferrin receptor have also made it an attractive choice for drug targeting
      and delivery of large protein-based therapeutics and toxins. Recent advances in
      elucidating the role of the intracellular controllers of transferrin recycling
      and sorting, such as Rab proteins and their effectors, have led to enhancement of
      transferrin receptor as a drug delivery vehicle. This review focuses on the use
      of transferrin receptor as an agent for facilitating drug delivery and targeting,
      and the role that mechanisms of transferrin receptor sorting and transcytosis
      play in these events.

PMID- 14597141
TI  - Current perspectives on the cellular uptake and trafficking of riboflavin.
AB  - The role of riboflavin in cell maintenance and growth, and the mechanism by which
      it is absorbed into various human tissues and cell lines has been extensively
      studied over the past decade. Evidence suggests two absorption mechanisms, a
      saturable-active component that dominates at near physiological vitamin
      concentrations and a passive component that is revealed at oversupplemented
      riboflavin conditions. Various transport modulator studies consistently suggest a
      highly riboflavin specific, temperature-dependent active transport mechanism that
      is regulated by the Ca2+/calmodulin pathway. The PKA and PKG pathways have also
      been implicated in absorption regulation. The long-standing model that riboflavin
      absorption involves a carrier-mediated transporter has recently been challenged
      through studies suggesting a receptor-mediated endocytic component. The presence
      of a soluble, human riboflavin binding protein in the transport stratagem has
      been shown to play an important role in fetal development. The relationship of
      this binding protein with the riboflavin specific membrane bound protein, though
      currently not well defined, may involve a protein-protein interaction that plays
      a primary role in this proposed receptor-mediated component.

PMID- 14597142
TI  - Endocytosis of adenovirus and adenovirus capsid proteins.
AB  - Key proteins of the icosahedral-shaped adenovirus (Ad) capsid mediate infection,
      and interact with cellular proteins to coordinate stepwise events of cell entry
      that produce successful gene transfer. Infection is mediated predominantly by the
      penton and fiber capsid proteins. The fiber initiates cell binding while the
      penton binds integrin coreceptors, triggering integrin-mediated endocytosis.
      Penton integrin signaling precedes viral escape from the endosomal vesicle. After
      cell binding, the virus undergoes stepwise disassembly of the capsid, shedding
      proteins during cell entry. Intracellular trafficking of the remaining capsid
      shell is mediated by the interaction of naked particles with the cytoskeleton.
      The capsid translocates toward the nucleus, with the majority of capsid proteins
      accumulating at the nuclear periphery, while viral DNA and associated protein VII
      are extruded through the nuclear pore. This discussion will encompass the current
      knowledge on Ad cell entry and trafficking, with an emphasis on the contribution
      of Ad capsid proteins to these processes. A greater understanding of the highly
      effective Ad cell entry pathway may lend itself to the development of safer drug
      and gene delivery alternatives utilizing similar pathways.

PMID- 14597143
TI  - Herpes simplex virion entry into and intracellular transport within mammalian
      cells.
AB  - Alphaherpesviruses, membrane-enveloped DNA viruses that are responsible for a
      host of human ailments, bind to, enter and are directly targeted to specific
      intracellular domains within their mammalian host cells. This review emphasizes
      recent work on the best studied of the alphaherpesviruses, Herpes simplex virus
      type 1 (HSV1). One area of focus is on recent work that has identified viral
      glycoproteins that are important in binding and internalization of the virus to
      the host cell. Complementary work on the receptors for those viral glycoproteins
      that reside on the host cell surface is also presented, with some discussion of
      how receptor variety might lead to the tissue tropism demonstrated by alphaherpes
      viruses. An additional area of focus in this review is how HSV uses the host cell
      transport systems to achieve intracellular targeting of the incoming virion
      toward the cell nucleus, and, after production of newly synthesized and assembled
      viral progeny, targeting them toward the plasma membrane for release.

PMID- 14597144
TI  - Aberrant sphingomyelin/ceramide metabolic-induced neuronal endosomal/lysosomal
      dysfunction: potential pathological consequences in age-related
      neurodegeneration.
AB  - Alterations in the trafficking and function of the endocytic pathway have been
      extensively documented to be one of the earliest pathological changes in sporadic
      Alzheimer's disease (AD). Although the pathophysiological consequences of these
      endosomal/lysosomal changes are currently unknown, several recent studies have
      suggested that such changes in endocytic function are able to cause a
      redistribution of several lysosomal hydrolases into early endosomes, leading to
      the overproduction of neurotoxic amyloid peptide. Recently, we and others have
      demonstrated that abnormal endocytic pathology within post-mitotic neurons can,
      in part, be attributed to alterations in sphingomyelin/ceramide metabolism,
      resulting in the intracellular accumulation of ceramide. Once inside the cell,
      the ability of ceramide to physically alter membrane structure, formation, and
      fusion, rather than serving solely as a lipid secondary messenger, may severely
      compromise normal endocytic trafficking. In this review, we will discuss the
      potential pathological effects of abnormal sphingomyelin/ceramide metabolism on
      intracellular vesicular transport in relation to both amyloid accumulation in AD
      and various neurodegenerative diseases associated with lysosomal abnormalities.

PMID- 14597145
TI  - Effect of nolomirole on monocrotaline-induced heart failure.
AB  - Neurohormonal activation has been shown to be a major factor in congestive heart
      failure progression and mortality. The beneficial effects obtained in clinical
      trials with angiotensin converting enzyme (ACE) inhibitors, beta-blockers and
      aldosterone antagonists have confirmed this hypothesis. 5,6-Diisobutirroyloxy-2
      methyl-aminotetraline hydrochloride (nolomirole) is a selective agonist of
      prejunctional D(2)-dopaminergic and alpha(2)-adrenergic receptors. The
      stimulation of these receptors inhibits catecholamine release from sympathetic
      nerve endings. To confirm that this mechanism can be useful in congestive heart
      failure, we studied the effects of nolomirole on monocrotaline-induced congestive
      heart failure. The ACE inhibitor trandolapril was used as reference compound.
      Rats were given single intraperitoneal injection of either saline (control group;
      n=20) or monocrotaline (50 mg kg(-1)). Three days later, the monocrotaline
      treated animals were randomly allocated (n=50 per group) to oral treatment with
      distilled water (vehicle group), nolomirole (0.25 mg kg(-1)) twice a day, or
      trandolapril (0.3 mg kg(-1)) once a day up to sacrifice. On the fourth week after
      monocrotaline injection, animals with signs of congestive heart failure were
      sacrificed for evaluation of heart hypertrophy and neuroendocrine alterations.
      Atrial natriuretic peptide (ANP) and alderosterone were determined by
      radioimmunoassay in plasma. Tissue norepinephrine concentration was quantified by
      high-pressure liquid chromatography. Nolomirole and trandolapril significantly
      reduced (a) hypertrophy of right atria and ventricles, (b) plasma levels of ANP
      and presence of pleural/peritoneal effusions and (c) norepinephrine depletion of
      right ventricle. These findings confirmed that nolomirole, like trandolapril, is
      able to attenuate the heart failure signs in the monocrotaline-induced congestive
      heart failure model.

PMID- 14597146
TI  - Peroxynitrite in reperfusion arrhythmias and its whole blood chemiluminescence
      results.
AB  - The aims of the present study were to investigate the effects of exogenous
      peroxynitrite (ONOO(-)) on reperfusion arrhythmias in anaesthetized rats, and to
      detect endogenous and exogenous ONOO(-)-induced chemiluminescence (CL) signals in
      rat whole blood, which was collected during baseline and in the first minute of
      reperfusion. ONOO(-) infusion in ischemia/reperfusion (I/R) applied groups caused
      significant decreases in mean arterial pressure (MAP) and heart rate (HR).
      Ventricular fibrillation (VF) incidences in the vehicle, ONOO(-), and dec-ONOO(-)
      infused groups were 63, 100, and 20%, respectively. In control group CL signal
      was 136+/-34mV during the resting period and was increased to 336+/-57mV with
      reperfusion. Also, the effects of SOD+CAT, L-NAME and urate were investigated.
      Ventricular tachycardia (VT) incidence was decreased significantly in SOD+CAT and
      urate; VF incidence was decreased significantly in SOD+CAT applied groups. CL
      signals were inhibited with SOD+CAT, L-NAME, and urate. Exogenous ONOO(-)
      infusion during I/R was also investigated. CL signal in exogenously ONOO(-)
      infused group is increased 423% during reperfusion. Only urate infused group VF
      incidence was decreased significantly. CL signals of ONOO(-) infused groups were
      inhibited by SOD+CAT, L-NAME, and urate. Based on the results of the current
      study, ONOO(-) seems to be one of the key mediators of reperfusion arrhythmias in
      anaesthetized rats.

PMID- 14597147
TI  - Anterior hypothalamic beta-adrenergic activity in the maintenance of hypertension
      in aortic coarctated rats.
AB  - The aim of this work was to demonstrate an alteration of the anterior
      hypothalamic catecholaminergic system in aortic coarctated (ACo) rats by the
      perfusion of beta-adrenergic antagonist and the microinfusion of beta-adrenergic
      agonist. Wistar urethane-chloralose anesthetized rats were used. The carotid
      artery was cannulated for blood pressure recording and changes in blood pressure
      were measured. A concentric microdialysis probe was inserted in the anterior
      hypothalamus. Metoprolol (a beta(1)-adrenoceptor antagonist) perfusion (6 microg
      ml(-1)) reduced the mean arterial pressure (MAP) in the ACo rats but not in sham
      operated (SO) animals. The anterior hypothalamic infusion of non-specific beta
      adrenergic agonist isoproterenol induced a dose-dependent decrease of blood
      pressure in both experimental groups, but the depressor response was
      significantly lower in ACo rats. The pretreatment with atenolol, a selective
      beta(1)-adrenoceptor antagonist, increased the depressor effect of isoproterenol
      in ACo rats, but not in SO rats. On the other hand, the hypotensive action of
      isoproterenol was significantly diminished after the administration of non
      specific beta-adrenoceptor antagonist propranolol in SO and ACo rats. The
      anterior hypothalamic infusion of clenbuterol, a selective beta(2)-adrenergic
      agonist, induced a dose-dependent decrease of blood pressure in both experimental
      groups. The depressor response to clenbuterol (1 nmol) was significantly lower in
      ACo rats than in SO rats. In summary, this study provides the evidence that there
      is a beta(1)-adrenergic compromise in anaesthetized ACo rats and this compromise
      may be involved in the maintenance of hypertension. On the other hand, this study
      also suggests the existence of pressor beta(1)-adrenoceptors in the anterior
      hypothalamic area of ACo rats but not in SO rats. We also found a diminished
      depressor beta(2)-adrenergic activity in ACo rats.

PMID- 14597148
TI  - Involvement of nitric oxide and prostaglandin pathways in the cardioprotective
      actions of bradykinin in rats with experimental myocardial infarction.
AB  - Bradykinin is a potent endothelium-dependent vasodilator in the coronary vascular
      bed. Endothelial mediators released by bradykinin include nitric oxide,
      prostacyclin and as yet unidentified endothelium-derived hyperpolarising factors.
      We wished to determine the involvement of nitric oxide and prostaglandin pathways
      in the cardioprotective actions mediated by bradykinin via the combined
      inhibition of ACE and aminopeptidase P (APP) in an in vivo rat model of acute
      ischemia (30 min) and reperfusion (4h). Myocardial infarct size was measured by
      using the staining agent 2,3,5-triphenyl tetrazolium chloride (TTC). Lipid
      peroxide levels in serum and in heart tissue were estimated
      spectrophotometrically. A lead II electrocardiogram was monitored at various
      intervals throughout the experiment. Infarct size reduction obtained with the
      combined inhibition of enalapril and apstatin, lisinopril and apstatin was
      blocked partially but significantly with the prior administration of L-NAME
      (Nomega-nitro-L-arginine methyl ester) or aspirin, suggesting the involvement of
      both nitric oxide and prostaglandin pathways in the cardioprotective actions
      mediated by bradykinin.

PMID- 14597149
TI  - Contractile effect of acetylcholine on isolated ampullar segment of Fallopian
      tubes.
AB  - The Fallopian tubes are scarcely innervated with cholinergic nerve fibers.
      Acetylcholine released from these nerves contracts smooth muscles of the tubes.
      The aim of our study was to investigate the effect of acetylcholine on the
      Fallopian tubes using selective antagonists in different hormonal settings. We
      have investigated effects of acetylcholine on isolated ampulla of Fallopian tubes
      taken from 83 patients during abdominal hysterectomy with adnexectomy. Twenty
      eight patients were in follicular, 36 were in luteal phase of menstrual cycle,
      and 19 patients were in menopause. Selective and non-selective muscarinic and
      nicotinic receptor blockers were used for investigation of the effects.
      Acetylcholine (from 1.8 to 658.6 microM/l) produced concentration-dependent tonic
      contraction of ampulla taken from the patients in follicular phase, luteal phase
      and menopause. The nicotinic receptor blocker mecamylamine (6.5 microM/l) and
      local anesthetic lidocaine (230.8 microM/l) did not affect the effect of
      acetylcholine. While M(1)- and M(2)-selective muscarinic receptor blockers
      pirenzepine (1.6 microM/l) and methoctramine (0.9 microM/l) did not show specific
      effect, atropine (0.01 microM/l) and selective M(3)-receptor blocker p-fluoro
      hexahydro-sila-difenidol (pFHHSiD, 0.2 microM/l) effectively blocked contractions
      caused by acetylcholine (maximal pA(2) values 9.74 and 7.54, respectively). The
      affinity of pFHHSiD for muscarinic receptors was highest in the follicular phase.
      The results of our study suggest existence of functional M(3) muscarinic
      receptors in ampulla of Fallopian tubes, located on the smooth muscle cells.

PMID- 14597150
TI  - Modulation of the activity of pro-inflammatory enzymes, COX-2 and iNOS, by
      chrysin derivatives.
AB  - Chrysin, a natural flavone compound found in plants, has anti-inflammatory
      activity that has been previously explained in part by the suppression of
      promoter activities of pro-inflammatory enzymes, cyclooxygenase-2 (COX-2) and
      inducible nitric oxide synthase (iNOS). Here we present evidence that several
      chrysin derivatives modulate the activities, as well as the expression, of COX-2
      and iNOS enzymes. Nitrate production triggered by lipopolysaccharide (LPS) was
      suppressed by treatment of cultured Raw264.7 cells (mice macrophage/monocyte)
      with chrysin, 5-hydroxy-7-methoxyflavone (Ch-2), and 5,7-diacetylflavone (Ch-4).
      Interestingly, COX-2 enzyme was strongly inhibited by Ch-4 (IC(50)=2.7 microM)
      but not by other derivatives. Furthermore, the inhibition of COX enzyme by Ch-4
      was selective for COX-2 over COX-1. Three-dimensional modeling showed that Ch-4
      fits well into the binding pocket of COX-2. The modeling suggested that a
      hydrogen bond exists between the oxygen of the ketone group at the 7-position of
      Ch-4 and the hydroxyl group of Tyr355. Docking Ch-4 into the V523I mutant of COX
      2 indicated that Ile523 of COX-1 might contribute to the selectivity of COX-2
      over COX-1. Ch-4 showed no effect on iNOS activity. Chrysin and Ch-2 weakly
      inhibited iNOS enzyme activity in the hemoglobin assay, but the underlying
      mechanisms of inhibition of iNOS by chrysin are not understood.

PMID- 14597151
TI  - Aminophylline therapy during endotoxemia in anesthetized spontaneously breathing
      rats.
AB  - Phosphodiesterase inhibitors, such as pentoxifylline and aminophylline, may
      reduce inflammatory cytokine-induced endothelial permeability. We tested the
      hypothesis that aminophylline treatment may ameliorate the pulmonary and
      extrapulmonary effects of endotoxemia in a rat model. In anesthetized rats, a
      tracheotomy was performed along with catheterization of a femoral vein and
      artery. Anesthesia, fluid balance, and normothermia were maintained throughout
      the 6-h experiment. A stable hemodynamic and gas-exchange baseline was
      established at which time the rats were randomly divided into three groups. Group
      I received aminophylline (1mg/kg) over 30 min followed by 0.5mg/kg/h. Group II
      received a single dose of endotoxin (4 mg/kg) while Group III received both
      aminophylline and endotoxin as described for Groups I and II, respectively. Gas
      exchange profiles, mean arterial blood pressure, and heart rate were determined
      every 2h. At hour 6, the rats were euthanized and lung, kidney, and heart tissue
      were removed for determination of water content. As our control group, we
      utilized data from our previously published study involving an identical surgical
      procedure with normal saline. Endotoxemia produced characteristic respiratory and
      hemodynamic signs of sepsis including hypotension, hyperventilation, tachycardia,
      and renal and pulmonary edema. Aminophylline treatment failed to prevent these
      endotoxemia-induced respiratory and hemodynamic manifestations of sepsis, but
      significantly improved the acid-base imbalance that developed during surgical
      procedures in saline-treated control rats. Further studies are warranted to
      determine potentially beneficial doses of aminophylline and resulting
      theophylline serum concentrations under such septic conditions.

PMID- 14597152
TI  - Paroxetine alters KCl- or ATP-induced contractile responses of isolated vas
      deferens in rats chronically treated with ethanol.
AB  - Chronic ethanol administration affects many organ systems, including sexual
      organs. One of these organs is the vas deferens whose contractility can also be
      altered by selective serotonin re-uptake inhibitors (SSRIs). The aim of the
      present study, is to evaluate whether paroxetine (PX), a SSRI, can modify the
      contractile responses of isolated vas deferens obtained from rats chronically
      treated with ethanol to the contractile agents, potassium chloride (KCl) and
      adenosine triphosphate (ATP). For 21 days, alcohol was applied with a modified
      liquid diet to sexually mature male Sprague-Dawley rats (200-240 g). The vas
      deferens of the rats were excised at the end of day 21 and suspended in the organ
      baths by classical pharmacological methods. The responses to contractile agents
      tested were decreased by chronic ethanol treatment in all groups compared to
      their untreated matches. PX (10(-7) and 10(-6)M) potentiated the contractions to
      KCl (20-180 mM) and ATP (10(-6) to 10(-3)M) in epididymal portion but its higher
      concentrations (10(-5) and 10(-4)M) inhibited the responses, both in the control
      and chronically ethanol treated rat groups. Prazosin (PR), an alpha adrenergic
      receptor blocker, could not inhibit PX-induced potentiation in lower
      concentrations of KCl but could inhibit the potentiation occurred at higher
      concentrations of KCl in epididymal portion both in the control and chronically
      ethanol treated rat groups. PR also inhibited PX-induced potentiation on the
      responses to ATP in epididymal portion both in the control and chronically
      ethanol treated rat groups. In conclusion, all the results obtained in this
      study, suggest that chronic ethanol treatment decreased the contractility of vas
      deferens but did not alter the action pattern of PX on responses to KCl and ATP
      in rat vas deferens. On the other hand, the potentiation of responses to
      contractile agents induced by PX can be partially considered as the result of
      inhibition of noradrenaline re-uptake.

PMID- 14597153
TI  - In vitro antioxidant properties of morphine.
AB  - Morphine is implicated in diverse functions, from development to immune
      modulation in the central and peripheral nervous systems. It has also been used
      extensively in the clinical management of pain due to its potent analgesic
      effect. This study was designed to evaluate the in vitro antioxidant capacity of
      morphine using different antioxidant tests, including total antioxidant activity,
      reducing power, free radical scavenging, superoxide anion radical scavenging,
      hydrogen peroxide scavenging and metal chelating activities. Morphine exhibited
      strong total antioxidant activity. The concentrations of 25, 50 and 75 microgml(
      1) of morphine showed 79.1, 84.3 and 92.3% inhibition on peroxidation of linoleic
      acid emulsion, respectively. On the other hand, at 75 microgml(-1) concentration
      of standard antioxidant, such as butylated hydroxyanisole (BHA), butylated
      hydroxytoluene (BHT) and alpha-tocopherol, exhibited 88.7, 94.5 and 70.4%
      inhibition on peroxidation of linoleic acid emulsion, respectively. In addition,
      morphine had effective reducing power, free radical scavenging, superoxide anion
      radical scavenging, hydrogen peroxide scavenging and metal chelating activities
      at the same concentrations (25, 50 and 75 microgml(-1)). These various
      antioxidant activities were compared to standard antioxidants such as BHA, BHT
      and alpha-tocopherol.

PMID- 14597154
TI  - The effect of alprostadil on ischemia-reperfusion injury of peripheral nerve in
      rats.
AB  - OBJECTIVE: To determine the effect of alprostadil on the ischemia-reperfusion
      (I/R) injury of the sciatic nerve in rats. MATERIALS AND METHODS: Pre-reperfusion
      administration of alprostadil (0.05 microg kg(-1)) was assessed in the I/R injury
      model of the rat sciatic nerve. In this model, blood samples were investigated
      for the I/R injury markers namely malondialdehyde (MDA), an indicator of lipid
      peroxidation, and nitrite/nitrate levels, products of nitric oxide (NO)
      metabolism. RESULTS: A significant decrease in MDA, and increase in NO levels
      were observed in the groups which received alprostadil before reperfusion, when
      compared to their corresponding untreated controls (I/R only) at all time
      intervals (P=0.0001). There was a statistically significant difference in both
      MDA, and NO levels between certain time intervals. There was no statistical
      linear correlation between MDA and NO levels. CONCLUSION: Alprostadil may be
      suggested as a protective anti-inflammatory and a vasodilator pharmacological
      agent for I/R injury in peripheral nerves. Also, measurements of NO and MDA may
      be complementary to the generally accepted evaluation parameters of I/R injury
      including electromyography and nerve histopathology.

PMID- 14597155
TI  - Cytotoxic effects of the mycotoxin beauvericin to human cell lines of myeloid
      origin.
AB  - Beauvericin, a cyclic hexadepsipeptide of potential importance to the health of
      humans and domestic animals, has been reported to exert cytotoxic effects on
      several mammalian cell types and to induce apoptosis. We investigated the
      cytotoxicity of this compound to two human cell lines of myeloid origin: the
      monocytic lymphoma cells U-937 and the promyelocytic leukemia cells HL-60. In
      some experiments HL-60 cells partially differentiated towards the eosinophilic
      phenotype were also used. Cultures of U-937 cells and HL-60 cells in stationary
      phase were exposed to beauvericin at concentrations ranging from 100 nM to 300
      microM for periods of time of 4 and 24h, respectively. The effects of beauvericin
      on cell viability were assessed by the Trypan blue exclusion method. In another
      set of experiments, performed with U-937 cells, the mycotoxin was included in the
      culture medium at passaging, in order to assess its possible effects on cell
      growth. Viability of both U-937 cells and HL-60 cells was not affected by
      beauvericin at concentrations up to 3 microM, after 4h exposure, whereas a steady
      decline was seen at higher concentrations. Similarly, after an exposure time of
      24h, a decline in viability was observed in cultures exposed to beauvericin at a
      concentration of 10 microM or higher. Thus, 50% cytotoxic concentrations at 24h
      of congruent with 30 microM and congruent with 15 microM were estimated for U-937
      cells and HL-60 cells, respectively.Similar experiments were performed with
      cultures of HL-60 cells partially differentiated towards the eosinophilic
      phenotype, revealing that, in 4h exposure experiments (but not in 24h
      experiments), the viability of these cultures underwent a significantly less
      pronounced decline, in comparison to undifferentiated HL-60 cultures.
      Interestingly, when U-937 cells were allowed to proliferate in the presence of
      the mycotoxin, included in the culture medium at passaging, a substantial
      cytotoxicity was observed at lower concentrations, compared with prevalently
      resting, stationary phase cultures. Accordingly, a definite inhibition of the
      proliferative capability of the cells was detected. The information provided by
      this work may be useful in selecting appropriate myeloid cell models for the
      development of biossays aimed at detecting beauvericin (and, possibly, other
      mycotoxins) in foods and other commodities.

PMID- 14597156
TI  - Folic acid and vitamin E supplementation effects on homocysteinemia, endothelial
      function and plasma antioxidant capacity in young myocardial-infarction patients.
AB  - We examined the effects of folate (either alone or co-supplemented with Vitamin
      E) on endothelial function in hyperhomocysteinimic patients and correlated
      results with serum antioxidant capacity. A randomized trial was carried out in 30
      young patients with recent acute myocardial infarction (AMI) and high plasma
      homocysteine concentrations. Intervention consisted of high doses of folate,
      either alone (group A) or in combination with Vitamin E (group B), for three
      months. Main outcome measures were endothelial function, serum antioxidant
      capacity, and homocysteinemia. Folic acid treatment reduced plasma homocysteine
      concentrations in both groups by 41% and, as compared with baseline values, was
      associated with a significant (P<0.001) improvement of endothelial function (from
      0.322 (0.03) to 0.450 (0.02)mm in group A and from 0.338 (0.03) to 0.584 (0.04)mm
      in group B). However, there was no difference in endothelial function improvement
      between folic acid and folic acid plus Vitamin E group. Plasma antioxidant
      capacity significantly (P<0.001) increased in both groups. In conclusion,
      beneficial effects of folic acid on vasomotion appear to be independent of
      antioxidant action but, rather, seem to be strongly associated with reduction of
      homocysteinemia. Confirming previous reports, the effects of Vitamin E are still
      equivocal.

PMID- 14597157
TI  - Drug therapeutic failures in emergency department patients. A university hospital
      experience.
AB  - Drug therapeutic failure (DTF) could be considered as an adverse drug reaction in
      which the expected drug effects do not occur following a prescribed
      pharmacological treatment, including any clinical event that could be related to
      a low prescribed dose or lack of compliance. DTFs are responsible for increasing
      disease length, hospitalisation time and social costs, with the worsening of
      patient quality of life. The aims of the present study are: (1) to estimate the
      frequency of DTFs among cases of adverse drug events referred to the emergency
      department; (2) to identify drug classes implicated in DTFs; (3) to analyse the
      putative causes underlying DTFs. Data presented in this paper were obtained from
      the Pronto Soccorso and Adverse Drug Events (PSADE) study carried out to analyse
      drug-related emergency department admissions in several Italian hospitals.
      Patients, admitted to the emergency department throughout two periods of 10 days
      each, were interviewed to gain information on their medical status and drug
      intake during the last two weeks. The present study analysed the patient
      questionnaires collected in the emergency department of Pisa University Hospital.
      Among 123 recorded cases of adverse drug event, 41 cases (19:22 male:female
      ratio; age range: 17-98 years, median age: 75 years) were identified as suspect
      DTF, resulting in a frequency of 33.33%. A statistical analysis was performed to
      evaluate the influence of two variables, class of patient age and number of drugs
      assumed, on DTFs. In accordance with the present findings, showing that the
      number of drugs assumed by a patient may increase the risk of DTF more than
      advanced age (odds ratio: 1.371, P<0.02; 1.295, P<0.03, respectively), the
      prescription of pharmacological combinations might be proposed as a main risk
      factor for DTF occurrence. In conclusion, our results suggest that DTFs represent
      an important cause of emergency department admission, particularly in elderly
      subjects treated with pharmacological associations.

PMID- 14597158
TI  - Bioequivalence assessment of ambroxol tablet after a single oral dose
      administration to healthy male volunteers.
AB  - A bioequivalence study of the ambroxol hydrochloride tablets was conducted.
      Twenty-four healthy male Korean volunteers received each medicine at the ambroxol
      hydrochloride dose of 30 mg in a 2 x 2 cross-over study. There was a 1-week
      washout period between the doses. Plasma concentrations of ambroxol were
      monitored by a high-performance liquid chromatography (HPLC) for over a period of
      24h after the administration. AUC(t) (the area under the plasma concentration
      time curve from time 0 to last sampling time, 24h) was calculated by the linear
      log trapezoidal rule method. C(max) (maximum plasma drug concentration) and
      T(max) (time to reach C(max)) were compiled from the plasma concentration-time
      data. Analysis of variance was carried out using logarithmically transformed
      AUC(t) and C(max), and untransformed T(max). The geometric mean of AUC(t) was
      495.8 ng ml(-1)h(-1) (test medication) and 468.3 ng ml(-1)h(-1) (reference
      medication). C(max) of 61.5 and 57.3 ng ml(-1) were achieved for the test and the
      reference medication, respectively. The point estimates and 90% confidence
      intervals for AUC(t) (parametric) and C(max) (parametric) were, in point estimate
      (90% confidence interval), 1.058 (0.989-1.134) and 1.073 (1.007-1.142),
      respectively, satisfying the bioequivalence criteria of the European Committee
      for Proprietary Medicinal Products and the US Food and Drug Administration
      Guidelines. The corresponding value of T(max) was 0.229 (0.015-0.444). These
      results indicate that the two medications of ambroxol hydrochloride are
      bioequivalent and, thus, may be prescribed interchangeably.

PMID- 14597159
TI  - Structure and organization of the genomic clone of a major peanut allergen gene,
      Ara h 1.
AB  - Peanut is one of the most allergenic foods. It contains multiple seed storage
      proteins identified as allergens, which are responsible for triggering IgE
      mediated allergic reactions. Ara h 1 is a major peanut allergen recognized by
      over 90% of peanut sensitive population. The objectives of this study were to
      isolate, sequence, and determine the structure and organization of at least one
      genomic clone encoding Ara h 1. Two 100 bp oligonucleotides were synthesized and
      used as probes to screen a peanut genomic library constructed in a Lambda FIX II
      vector. After three rounds of screening, four putative positive clones were
      selected and their DNA digested with SacI. A unique 12-13 kb insert fragment was
      released, confirmed positive by Southern hybridization, subcloned into a
      pBluescript vector, and sequenced. Sequence analysis revealed a full-length Ara h
      1 gene of 4447 bp with four exons of 721, 176, 81 and 903 bp and three introns of
      71, 249 and 74 bp. The deduced amino acid encodes a protein of 626 residues that
      is identical to the Ara h 1 cDNA clone P41b. Several well characterized elements
      for promoter strength were found in the promoter region of Ara h 1 and include
      two TATA-boxes (TATATAAATA and TTATATATAT) at positions -89 and -348,
      respectively; a CAAT-box (CAAT) at position -133, a GC-box (CGGGACCGGGCCGG
      GCCTTCGGGCCGGGCCGGGT) at position -475, two G-boxes (TAACACGTACAC and
      ATGGACGTGAAA) at positions -264 and -1808, respectively; two RY elements (CATGCAC
      and CATGCAT) at positions -235 and -278, respectively; and other cis-element
      sequences. In the 3' UTR, a poly-A signal (AATAAA) was found at +2350, two
      additional stop codons (TAA) at +2303 and +2306, and TTTG/CTA/G motifs. Three
      introns and a potentially strong promoter could explain the high expression of
      the Ara h 1 gene. Amino acid sequence comparisons revealed high sequence
      similarity with other plant vicilins, member of the cupin superfamily.

PMID- 14597160
TI  - Translocations into human chromosome 14 JH region: factors influencing downstream
      abortive immunoglobulin class switching.
AB  - Bcl-2 translocations in follicular lymphomas (FL) are often associated with
      downstream immunoglobulin class switch recombination (CSR) on the translocated
      allele. We studied cell lines with different translocations into the IgH locus to
      gauge any common features associated with downstream CSR events. CSR associated
      with chromosomal rearrangements was observed in cells (RL) with translocations
      similar to those frequently observed in FL (bcl-2-JH), and such CSR was also seen
      with a myc (near exon 1)-JH5 intron translocation (MC116), but not for far 5'-myc
      JH5 intron (P3HR-1) or myc-Smu translocations (Ramos). Both MC116 and P3HR-1 myc
      translocations showed evidence for an origin from somatic hypermutation.
      Therefore, the association of JH translocations with CSR on the translocated
      allele is unlikely to be linked with specific translocation mechanisms, and the
      P3HR-1 configuration indicated that the downstream class switching is not a
      necessary consequence of (or precondition for) such a translocation event. MC116
      and RL, but not P3HR-1 cells, showed constitutive transcription through the
      translocated IgH alleles, suggesting that transcription through this region or
      the processing of such transcripts may promote CSR. However, while CSR events
      clearly occurred in the precursors of MC116 and RL, neither cell line could
      undergo complete class switching.

PMID- 14597161
TI  - Differential binding to human FcgammaRIIa and FcgammaRIIb receptors by human IgG
      wildtype and mutant antibodies.
AB  - We are investigating the interactions of recombinant human IgG antibodies with Fc
      receptors to enable selection of a constant region giving minimal depletion of
      antigen-bearing cells. Eight variant constant regions were made by substituting
      motifs between human IgG subclasses in the lower hinge region and/or a specially
      close loop of the CH2 domain. Mutations in the lower hinge region were shown to
      eliminate FcgammaRI binding and monocyte activation [Eur. J. Immunol. 29 (1999)
      2613]. Here, we detail interactions with FcgammaRIIa of the 131R and 131H
      allotypes and FcgammaRIIb. Lower hinge mutations caused large reductions in
      binding whereas modification of residues 327, 330 and 331 had less dramatic
      effects. However, like the wildtype IgG subclass binding hierarchies, the effect
      of the mutations varied between different receptors. We identified IgG1 variants
      which react with the activating receptor, FcgammaRIIa, at least 10-fold less
      efficiently than wildtype IgG1 but whose binding to the inhibitory receptor,
      FcgammaRIIb, is only four-fold reduced. Manipulation of interactions with
      FcgammaRIIb separately from those with activating receptors provides potential
      for designing antibodies with novel and effective combinations of attributes. In
      addition, insight is gained into the evolution of functional differences in human
      IgG subclasses.

PMID- 14597162
TI  - Immune deposition of C1q and anti-C1q antibodies in the kidney is dependent on
      the presence of glomerular IgG.
AB  - Anti-C1q autoantibodies are found frequently in patients with Systemic Lupus
      Erythematosus (SLE) and several studies indicate that these autoantibodies are
      associated with renal involvement. We have shown earlier that administration of
      anti-C1q antibodies to normal BALB/c mice results in the deposition of these
      antibodies and C1q in the kidney. In the present study we have investigated which
      factors are essential for this C1q-anti-C1q deposition. Injection of anti-C1q
      antibodies in C57BL/6 mice results in deposition of both C1q and anti-C1q in
      glomeruli, while administration of equal concentrations of anti-C1q to
      immunoglobulin deficient Rag2-/- mice did not result in deposition of anti-C1q
      antibodies. Analysis of renal sections of naive Rag2-/- mice revealed absence of
      mouse IgG and C1q in the glomeruli, while circulating C1q was within normal
      levels. Reconstitution of Rag2-/- mice with IgG, either by injection with
      purified mouse IgG or by splenocyte transfer, resulted in restored localization
      of mouse IgG together with C1q in the kidney. Subsequent injection of anti-C1q
      antibodies in these IgG reconstituted mice resulted in clear deposition of C1q
      together with anti-C1q in the kidneys comparable to that found in C57BL/6 mice
      receiving anti-C1q. We propose that the continuous presence of serum derived non
      immune IgG in the glomerulus serves as a target for low affinity interactions
      with C1q, which then can serve as antigen for anti-C1q antibodies. Therefore we
      hypothesize that high and fluctuating levels of IgG as observed in patients with
      SLE may contribute to flares of renal inflammation in those patients with anti
      C1q autoantibodies.

PMID- 14597163
TI  - Priming by recombinant chicken interleukin-2 induces selective expression of IL-8
      and IL-18 mRNA in chicken heterophils during receptor-mediated phagocytosis of
      opsonized and nonopsonized Salmonella enterica serovar enteritidis.
AB  - Heterophils, the principal avian polymorphonuclear leukocytes (PMNs) equivalent
      to the mammalian neutrophil, function as professional phagocytes against
      bacterial infections, mediate acute inflammation, and respond to cytokine
      stimulation to aid in regulation of innate host defenses. Interleukin-2 (IL-2)
      has been found to exercise an array of biological effects on other cell types
      besides T lymphocytes, including NK cells, B cells, monocytes, and neutrophils.
      In the present experiments, using real-time quantitative RT-PCR, we evaluated the
      role of rChIL-2 as a priming mediator controlling heterophil responses at the
      level of gene transcription by examining the expression of mRNA for pro
      inflammatory (IL-1beta, IL-6, IL-8) and Th1 (IL-18 and IFN-gamma) cytokine genes
      following stimulation with phagocytosis agonists; i.e., opsonized and
      nonopsonized Salmonella enteritidis. Peripheral blood heterophils were isolated
      and incubated with rChIL-2 from transfected COS cells. rChIL-2 selectively primed
      the heterophils for an increase in transcription of the pro-inflammatory cytokine
      IL-8 and of the Th1 cytokine IL-18 induced by all three phagocytic agonists.
      Although rChIL-2 priming modulated the expression of specific cytokine mRNA in
      heterophils stimulated by different phagocytic agonists, the rChIL-2 by itself
      did not directly induce gene expression of either the pro-inflammatory or Th1
      cytokines. We propose that rChIL-2 could be priming heterophils solely to
      function as more efficient innate effector cells to limit bacterial growth
      through the selective increase of IL-8 and IL-18 gene expression.

PMID- 14597164
TI  - Cloning and sequence analysis of cDNA for the proteasome activator PA28-beta
      subunit of flounder (Paralichthys olivaceus).
AB  - Proteasome is a large multisubunit complex involved in intracellular proteolysis
      in antigen processing for loading MHC class I molecules. Two activators PA28
      alpha and PA28-beta, which are induced by interferon-gamma (IFN-gamma), activate
      this latent enzyme complex. Genes encoding these activators, PSME1 and PSME2,
      respectively, have been characterized from various mammalian but only from
      zebrafish among piscine. We have cloned a PSME2 gene homologue from a leukocyte
      cDNA library of flounder, a marine fish. The flounder PSME2 gene (fPSME2)
      encompasses 1063 nucleotides and encodes a polypeptide of 242 amino acids (aa),
      with a deduced molecular weight of 27.2 kDa. The deduced protein has 82% sequence
      similarity to that of zebrafish and 73-74% sequence similarity to that of various
      mammalians and shows higher level sequence homology in the C-terminal region.
      There was a PA28-beta protein subunit-specific insert located at the
      corresponding to the KEKE motif of PA28-alpha protein. A phylogenetic tree
      derived using deduced amino acid sequences showed a diversion of piscine PSME2
      from mammalian counterpart after diversion of PSME1 and PSME2 from a common
      ancestral gene. Northern blot analysis revealed a higher level expression of
      fPSME2 gene in kidney, spleen and muscle tissues of bacterial lipopolysaccharide
      (LPS) stimulated flounder than those from non-induced flounder.

PMID- 14597165
TI  - Characterization and molecular modeling of a highly stable anti-Hepatitis B
      surface antigen scFv.
AB  - We raised a mouse monoclonal antibody (5S) against the 'a' epitope of the
      Hepatitis B surface antigen (HBsAg) by selecting for binding of the hybridoma
      supernatant in conditions that usually destabilize protein-protein interactions.
      This antibody, which was protective in an in vitro assay, had a high affinity
      with a relative dissociation constant in the nanomolar range. It also displayed
      stable binding to antigen in conditions that usually destabilize antigen-antibody
      interactions, like 30% DMSO, 8 M urea, 4 M NaCl, 1 M guanidium HCl and extremes
      of pH. The variable regions of the antibody were cloned and expressed as an
      single chain variable fragment (scFv) (A5). A5 had a relative affinity comparable
      to the mouse monoclonal and showed antigen binding in presence of 20% DMSO, 8 M
      urea and 3 M NaCl. It bound the antigen in the pH range of 6-8, though its
      tolerance for guanidium HCl was reduced. Sequence analysis demonstrated a
      significant increase in the frequency of somatic replacement mutations in CDRs
      over framework regions in the light but not in the heavy chain. A comparison of
      the molecular models of the variable regions of the 5S antibody and its germ-line
      precursor revealed that critical mutations in the heavy and light chains
      interface resulted in better inter-chain packing and in the movement of CDR H3
      and CDR L1 from their germline positions, which may be important for better
      antigen binding. In addition to providing a reagent for neutralizing for the
      virus, such an antibody provides a model for the evolution of stable high
      affinity interaction during antibody maturation.

PMID- 14597166
TI  - NF-kappaB and c-Jun-dependent regulation of macrophage inflammatory protein-2
      gene expression in response to lipopolysaccharide in RAW 264.7 cells.
AB  - Macrophage inflammatory protein-2 (MIP-2) is a mouse C-X-C chemokine that plays
      an important role in the recruitment of neutrophils. Transcription of the MIP-2
      gene is rapidly induced by lipopolysaccharide (LPS) stimulation in cells of
      macrophage lineage. We show here that the MIP-2 promoter is transcriptionally
      activated in a macrophage cell line RAW 264.7 by LPS through a sequence located
      between -450 and -54 and this region contains two copies of activator protein-1
      (AP-1) and one copy of nuclear factor-kappaB (NF-kappaB) binding site. A MIP-2
      promoter-reporter was activated by ectopical expression of NF-kappaB p65 or c-Jun
      transcription factors. Inhibition of NF-kappaB nuclear localization by co
      expression of a mutant IkappaBalpha protein (IkappaBalpha super repressor,
      IkappaBalphaSR) blocked LPS-induced transcription from a MIP-2 promoter-reporter
      construct, showing that NF-kappaB activation is required for MIP-2 gene
      expression in the LPS-signaling pathway. By deletion analysis of the MIP-2
      promoter region, we show that NF-kappaB and c-Jun binding sites are essential for
      LPS-induced MIP-2 gene expression. Using transient transfection, NF-kappaB and c
      Jun transcription factors were found to synergistically activate the MIP-2
      promoter. In summary, our data suggest that both NF-kappaB and c-Jun contribute
      to LPS-induced mouse MIP-2 gene expression in RAW 264.7 cells.

PMID- 14597167
TI  - Transcriptional control during mammalian anterior pituitary development.
AB  - The mammalian anterior pituitary gland is a compound endocrine organ that
      regulates reproductive development and fitness, growth, metabolic homeostasis,
      the response to stress, and lactation, by actions on target organs such as the
      gonads, the liver, the thyroid, the adrenals, and the mammary gland. The protein
      and peptide hormones that control these physiological parameters are secreted by
      specialized pituitary cell types that derive from a common origin in the early
      ectoderm. Collectively, the broad physiological importance of the pituitary
      gland, its intriguing organogenesis, and the clinical and agricultural
      significance of its actions, have established pituitary development as an
      excellent model system for the study of the gene-regulatory cascades that guide
      vertebrate cell determination and differentiation. We review the transcriptional
      pathways that regulate the commitment of the individual pituitary cell lineages
      and that subsequently modulate trophic hormone gene activity in the
      differentiated cells of the mature gland.

PMID- 14597168
TI  - Molecular comparison of rat cyclic nucleotide phosphodiesterase 8 family: unique
      expression of PDE8B in rat brain.
AB  - Cyclic nucleotide phosphodiestease (PDE) type 8 is categorized into a family of 3
      isobutyl-1-methylxanthine-insensitive PDE hydrolyzing cAMP with high affinity. We
      have isolated cDNAs encoding rat PDE8A and PDE8B from brain and testis,
      respectively. The sequence analysis demonstrated that rat PDE8A was a protein of
      823 amino acid residues. Rat PDE8B protein was predicted as an N-terminal
      truncated form of 760 amino acid residues. Both of rat PDE8 proteins include REC,
      PAS and catalytic PDE domains. Tissue-specific expression patterns of rat PDE8A
      and PDE8B transcripts were demonstrated by Northern blot analysis. Rat PDE8A
      transcripts were rich in the liver and testis, and those of rat PDE8B were
      particularly abundant in the brain and were not expressed in the thyroid gland,
      while human thyroid gland contains PDE8B transcripts at a high level. Rat PDE8B
      transcripts were found in all brain regions other than cerebellum and shown to
      exist in the neuronal cells in in situ hybridization. Mouse PDE8B1 sequence was
      also identified by a database search and sequence alignment, revealing a protein
      of 885 amino acid residues, which is 99% and 96% identical to rat and human
      PDE8B1, respectively. As well as rat PDE8B, expression of mouse PDE8B transcripts
      was not confined to the thyroid gland. Species-dependent tissue expression
      pattern was quite unique features of PDE8B.

PMID- 14597170
TI  - Characterization and transcriptional profiles of three Spodoptera frugiperda
      genes encoding cysteine-rich peptides. A new class of defensin-like genes from
      lepidopteran insects?
AB  - The present work describes sequence and transcription of three Spodoptera
      frugiperda genes encoding 6-cysteine-rich peptides. Sequence alignments indicate
      that the predicted peptides belong to the insect defensin family, although
      phylogenetic analyses suggest they form a cluster distinct from that of other
      neopteran insect defensins. The three genes were identified in a non-immune
      challenged Sf9 cells cDNA (DNA complementary to RNA) library (Landais et al.,
      Bioinformatics, in press) and were named spodoptericin, Sf-gallerimycin and Sf
      cobatoxin. Spodoptericin is a novel defensin-like gene that appears to be weakly
      up-regulated following injection of bacteria and fungi. Interestingly, no
      sequence motif clearly homologous to cis regulatory element involved in the
      regulation of antimicrobial genes was found. An homologue of the spodoptericin
      gene was identified in the SilkBase Bombyx mori cDNA library. Sf-gallerimycin is
      related to the Galleria mellonella gallerimycin gene and is induced after immune
      challenge by injection of bacteria in the larval fat body as well as in
      hemocytes. In silico analysis of the sequence upstream from the cDNA reveals the
      presence of at least one motif homologous to a nuclear factor kappaB (NF-kappaB)
      binding site. Finally, Sf-cobatoxin is related to the G. mellonella cobatoxin
      like gene. Despite high levels of constitutive expression compared to the two
      previous genes, transcription of Sf-cobatoxin is increased after immune, in
      particular, bacterial challenge. We therefore confirm that these three genes
      encode potential candidate molecules involved in S. frugiperda innate humoral
      response.

PMID- 14597169
TI  - SNCF, a SoxNeuro interacting protein, defines a novel protein family in
      Drosophila melanogaster.
AB  - The involvement of the Sox family of transcription factors in the development of
      the central nervous system (CNS) appears to be conserved in invertebrates and
      vertebrates. In Drosophila, SoxNeuro (SoxN) was recently shown to be involved in
      the formation of neuroblasts [Development 129 (2002) 4193; Development 129 (2002)
      4219]. Through a yeast two-hybrid assay searching for proteins interacting with
      SoxN, we have isolated a novel protein in Drosophila, SoxNeuro Co-Factor (SNCF).
      The expression of the SNCF gene was detected during early embryogenesis at the
      blastoderm stages, and stopped just at the beginning of gastrulation. In
      transfected cells, the protein localised to nuclei, and strongly accumulated in
      nucleoli. SNCF was able to enhance SoxN mediated transcriptional activity in
      transfected cells, suggesting that SNCF might act as a SoxN co-activator.
      Finally, data are presented showing the existence in Drosophila of several
      proteins with a domain of homology to SNCF, which are all expressed early in
      embryogenesis at the blastoderm stage.

PMID- 14597171
TI  - An intronic endogenous retrovirus-like sequence attenuates human haptoglobin
      related gene expression in an orientation-dependent manner.
AB  - The human haptoglobin-related gene (HPR) gene codes for a haptoglobin-related
      protein (Hpr), a component of trypanosome lytic factor which circulates in plasma
      in small quantities. Except for the presence of a retrovirus-like element, RTVL
      Ia, in intron 1, HPR is 92% identical in sequence to the closely linked human
      haptoglobin gene (HP) gene coding for haptoglobin. We have explored
      experimentally in tissue culture and in vivo in mice and in humans the influence
      of the retroviral-like sequence type Ia (RTVL-Ia) element on HPR expression.
      Transient expression in HepG2 cells of plasmids carrying the HPR promoter joined
      by a shortened version of intron 1 to the chloramphenicol acetyltransferase (CAT)
      vector showed that fragments containing the 5' long terminal repeat (LTR) had no
      significant effect. In contrast, a gag-pol related part and a pol-env-3'LTR
      related part of RTVL-Ia decreased expression to 20% and 40% of that in their
      absence but only when they were in naturally occurring orientation. The latter
      fragment that contains sequences reminiscent of elements essential for retrovirus
      viability, such as a splicing acceptor site, TATA box and polyA addition signal
      sequence, was further tested in site-specific transgenic mice. Similar to in
      vitro experiment, insertion of this fragment into an HPR transgene in mice
      reduced HPR expression to 50% compared to a transgene without the insert, but
      none of the viral sequence motifs appear to explain this effect. Instead, we
      found within the fragment two cryptic splicing donor sites whose products were
      present in transgenic mouse and in human liver RNA. Our data suggest that a
      combination of multiple small effects of RTVL-Ia including aberrant splicing
      accounts for the low (6%) expression of the present-day HPR relative to HP.

PMID- 14597172
TI  - The Bacillus subtilis Gne (GneA, GalE) protein can catalyse UDP-glucose as well
      as UDP-N-acetylglucosamine 4-epimerisation.
AB  - Mutations in the Bacillus subtilis gene that affect the activity of the uridine
      diphosphate (UDP)-N-acetylglucosamine (GlcNAc) 4-epimerase (EC 5.1.3.7) were
      shown to map to galE, the structural gene of the UDP-glucose (Glc) 4-epimerase
      (EC 5.1.3.2). This genetic evidence that the same enzyme can catalyse the
      epimerisation of hexoses as well as of their N-acetylated forms is confirmed by
      in vitro assays with purified enzyme. It appears that in B. subtilis, Gne (GneA,
      GalE) is involved in two distinct and essential functions, i.e., cell
      detoxification under certain growth conditions and the biosynthesis of anionic
      cell wall polymers. We discuss the evidence that such enzymes capable of
      utilizing both UDP-hexoses and UDP-N-acetylhexosamines are present in other
      organisms.

PMID- 14597173
TI  - Genetic characterization of the styrene lower catabolic pathway of Pseudomonas
      sp. strain Y2.
AB  - Pseudomonas sp. strain Y2 is a styrene-degrading bacterium, which initiates the
      catabolism of this compound via its transformation into phenylacetate by the
      sequential oxidation of the vinyl side chain. The styrene upper catabolic gene
      cluster (sty genes) had been localized in a 9.2-kb chromosomal region. This
      report describes the isolation, sequencing and analysis of an adjacent 20.5-kb
      chromosomal region that contains the genes of the styrene lower degradative
      pathway (paa genes), which are involved in the transformation of phenylacetate
      into aliphatic compounds that can enter the Krebs cycle. Hence, Pseudomonas sp.
      strain Y2 becomes the first microorganism whose entire styrene catabolic cluster
      has been completely characterized. Analysis of the paa gene cluster has revealed
      the presence of 17 open reading frames as well as gene duplications and gene
      reorganizations that are absent in other phenylacetate catabolic clusters
      described so far. The functionality of these genes has been proved by means of
      both complementation experiments on Pseudomonas putida mutants and in vitro
      enzymatic assays. Moreover, a DNA cassette encoding the whole styrene lower
      pathway has been constructed and has been used to expand the ability of
      Pseudomonas strains to degrade phenylacetic acid. For the first time, two
      functional phenylacetate-CoA ligases have been identified in an aerobic
      phenylacetic acid degradation pathway. Although the upper and lower styrene
      catabolic clusters are adjacent in the Pseudomonas sp. strain Y2 chromosome,
      their particular base composition and codon usage suggest a distinct evolutionary
      history.

PMID- 14597174
TI  - Characterization of the rat cytoplasmic C1-tetrahydrofolate synthase gene and
      analysis of its expression in liver regeneration and fetal development.
AB  - The eukaryotic trifunctional enzyme, C(1)-tetrahydrofolate (THF) synthase,
      interconverts folic acid derivatives between various oxidation states and is
      critical for normal cellular function, growth, and differentiation. Using a rat
      C(1)-THF synthase cDNA and synthetic oligonucleotides, the rat C(1)-THF synthase
      gene was isolated and characterized. The gene consists of 28 exons and spans 67.5
      kbp. Primer extension, RNase protection, and rapid amplification of cDNA ends
      (RACE) experiments indicate the presence of multiple transcription start points
      (tsp) within a 250-bp window located between 50 and 300 bp upstream from the
      start codon. The 5' flanking region is devoid of a TATA consensus sequence motif,
      but putative regulatory elements, including NF-kappabeta, HNF-4alpha1, RARalpha1,
      C/EBP, and PPAR are present in the promoter region. The 5' flanking region also
      contains two sets of tetranucleotide repeats and two short interspersed nuclear
      elements (SINES). The initial 2500 bp of 5' flanking sequences of the rat and
      mouse cytoplasmic C(1)-THF synthase genes share 70% identity. However, comparison
      with the human gene from the Human Genome Data Bank revealed no significant
      homology in the 5' flanking region. The gene structure characterization led to
      the identification of a pseudogene that is 94% identical to the C(1)-THF synthase
      gene and probably diverged 10-12 million years ago. In addition, the gene
      expression patterns of C(1)-THF synthase were investigated during liver
      regeneration and liver and kidney organogenesis, two highly regulated events. In
      both processes, C(1)-THF synthase expression correlated with increased nucleotide
      metabolism. This pattern suggests that the gene is regulated in response to
      changes in the demand for folate-dependent one-carbon units.

PMID- 14597175
TI  - The pyruvate dehydrogenase complex of Mycoplasma hyopneumoniae contains a novel
      lipoyl domain arrangement.
AB  - The genes encoding the pyruvate dehydrogenase (PDH) complex (pdhA, pdhB, pdhC and
      pdhD) from Mycoplasma hyopneumoniae have been cloned and sequenced. The genes are
      arranged into two operons, designated pdhAB and pdhCD, which are not found
      together in the chromosome. The pdhA, pdhB, pdhC and pdhD genes encode proteins
      of predicted molecular masses of 44.2 kDa (pyruvate dehydrogenase major subunit;
      E1alpha), 36.6 kDa (pyruvate dehydrogenase minor subunit; E1beta), 33.1 kDa
      (dihydrolipoyl acetyltransferase; E2) and 66.3 kDa (dihydrolipoyl dehydrogenase;
      E3), respectively. Sequence analysis of the pdhCD operon revealed the presence of
      a lipoyl-binding domain in pdhD but not in pdhC. The lipoyl domain is believed to
      act as a "swinging arm" that spans the gaps between the catalytic domains of each
      of the subunits. Portions of the N-terminal regions of pdhA and pdhD were
      expressed as 6xHis-tag fusion proteins in Escherichia coli and purified by nickel
      affinity chromatography. The purified proteins were used to raise antibodies in
      rabbits, and Western blot analysis was performed with the polyclonal rabbit
      antiserum. Both the pdhA and pdhD genes were expressed among various strains of
      M. hyopneumoniae as well as the porcine mycoplasmas, Mycoplasma hyorhinis and
      Mycoplasma flocculare. Southern hybridisation analysis using probes from pdhA and
      pdhD detected one copy of each gene in the chromosome of M. hyopneumoniae. Since
      previous studies have shown pyruvate dehydrogenase activity in M. hyopneumoniae
      [J. Gen. Microbiol. 134 (1988) 791], it appears likely that a functional lipoyl
      binding domain in the N terminus of PdhC is not an absolute prerequisite for
      pyruvate dehydrogenase enzyme activity. We hypothesise that the lipoyl-binding
      domain of PdhD is performing the enzymatic function normally attributed to the
      PdhC lipoyl-binding domain in other organisms. Searches of pyruvate dehydrogenase
      gene sequences derived from other Mycoplasma species showed that a putative
      lipoyl domain was absent in the pdhC gene from Mycoplasma pulmonis. However, like
      other bacterial species, pdhC gene sequences from Mycoplasma capricolum,
      Mycoplasma genitalium and Mycoplasma pneumoniae contain a putative lipoyl domain.

PMID- 14597176
TI  - Thioredoxin-mediated redox control of the transcription factor Sp1 and regulation
      of the thioredoxin gene promoter.
AB  - In recent years, redox control has emerged as a fundamental mechanism of gene
      regulation through transcriptional control. Thioredoxin (Trx) is a dithiol
      reducing enzyme known to be involved in the redox regulation of a number of
      transcription factors, and in this study, we have investigated the redox
      dependent regulation of the DNA binding activity of Sp1 by thioredoxin.
      Electrophoretic mobility shift assays were used to show that both recombinant Sp1
      produced in Escherichia coli and endogenous Sp1 expressed by MDA-MB-231 breast
      cancer cells is subject to redox regulation. We found that thioredoxin alone or
      in conjunction with the full thioredoxin system (comprising thioredoxin,
      thioredoxin reductase [TR], and alpha-nicotinamide adenine dinucleotide phosphate
      [NADPH]) can increase Sp1 DNA binding activity in vitro to an oligonucleotide
      containing the Sp1 consensus sequence. Furthermore, we have provided evidence
      that recombinant Sp1 can bind to Sp1 consensus sequences within a 330-base pair
      (bp) thioredoxin promoter fragment and that this interaction can also be enhanced
      by the presence of thioredoxin. Luciferase reporter assays using this same
      minimal thioredoxin promoter region demonstrated that both Sp1 and Sp3 can bind
      to the promoter and act to enhance transcription. When the three identified Sp1
      consensus sequences within the reporter construct were deleted, there was a loss
      of basal promoter activity, showing that these closely positioned sites are
      important for regulation of thioredoxin gene expression.

PMID- 14597178
TI  - Detecting excess radical replacements in phylogenetic trees.
AB  - There are a few instances in which positive Darwinian selection has been
      convincingly demonstrated at the molecular level. In this study, we present a
      novel test for detecting excess of radical amino-acid replacements. Such excess
      is usually indicative of positive Darwinian selection, but may also be due to
      relaxed functional constraints or model misspecification. In our test, each amino
      acid replacement is characterized in terms of a physicochemical distance, i.e.,
      the degree of dissimilarity between the exchanged amino-acid residues. By using
      phylogenetic trees based on protein sequences, our test identifies statistically
      significant deviations of the mean physicochemical distance from the random
      expectation, either along a taxonomic lineage or across a subtree. The mean
      inferred distance is calculated as the average physicochemical distance over all
      possible ancestral sequence reconstructions weighted by their likelihood. Our
      method substantially improves over previous approaches by taking into account the
      stochastic process, tree phylogeny, among-site rate variation, and alternative
      ancestral reconstructions. We provide a fast linear time algorithm for applying
      this test to all branches and all subtrees of a given phylogenetic tree. We
      validate this approach by applying it to two well-studied datasets: the MHC class
      I glycoproteins serving as a positive control, and the house-keeping gene
      carbonic anhydrase I serving as a negative control.

PMID- 14597177
TI  - Proliferation-linked expression of the novel murine gene m4mbt encoding a nuclear
      zinc finger protein with four mbt domains.
AB  - Here we describe the cloning and characterization of a novel murine gene named
      m4mbt that encodes a homolog of the lethal (3) malignant brain tumor (l(3)mbt)
      and Scm proteins. It is localized on mouse chromosome 15E2 and is organized into
      17 exons. As demonstrated by Northern blot analysis, m4mbt mRNA is expressed in
      virtually all tested tissues and cell lines with the exception of stomach and
      muscle. The m4mbt transcript was most abundant in the testes. m4mbt expression
      was shown to initiate early during mouse embryonal development (before day 7) and
      continue until adulthood. The expression of m4mbt mRNA also appears to correlate
      with cellular proliferation, since we observed down-regulation of m4mbt
      expression during terminal monocytic differentiation and in contact-inhibited
      fibroblasts. Computer analysis of the amino acid (aa) sequence revealed that the
      M4mbt protein comprises an amino-terminally located atypical C2C2 zinc finger and
      four centrally located mbt repeats. Mbt repeats are also found in proteins of the
      Polycomb group (PcG) that associate with heterochromatin and function as long
      term repressors of transcription. Using Western blot analysis and confocal
      fluorescent microscopy, we demonstrated that the M4mbt protein is localized in
      the nucleus. Since M4mbt has structural domains similar to chromatin-associated
      proteins, its expression is associated with proliferation, and it has a nuclear
      localization, it may have a regulatory role related to proliferation and/or
      differentiation.

PMID- 14597179
TI  - A cluster of novel serotonin receptor 3-like genes on human chromosome 3.
AB  - The ligand-gated ion channel family includes receptors for serotonin (5
      hydroxytryptamine, 5-HT), acetylcholine, GABA, and glutamate. Drugs targeting
      subtypes of these receptors have proven useful for the treatment of various
      neuropsychiatric and neurological disorders. To identify new ligand-gated ion
      channels as potential therapeutic targets, drafts of human genome sequence were
      interrogated. Portions of four novel genes homologous to 5-HT(3A) and 5-HT(3B)
      receptors were identified within human sequence databases. We named the genes 5
      HT(3C1)-5-HT(3C4). Radiation hybrid (RH) mapping localized these genes to
      chromosome 3q27-28. All four genes shared similar intron-exon organizations and
      predicted protein secondary structure with 5-HT(3A) and 5-HT(3B). Orthologous
      genes were detected by Southern blotting in several species including dog, cow,
      and chicken, but not in rodents, suggesting that these novel genes are not
      present in rodents or are very poorly conserved. Two of the novel genes are
      predicted to be pseudogenes, but two other genes are transcribed and spliced to
      form appropriate open reading frames. The 5-HT(3C1) transcript is expressed
      almost exclusively in small intestine and colon, suggesting a possible role in
      the serotonin-responsiveness of the gut.

PMID- 14597180
TI  - B1 and related SINEs in mammalian genomes.
AB  - Although B1 and Alu were the first discovered Short Interspersed Elements
      (SINEs), the studies of these genomic repeats were mostly limited to mice and
      humans and little data on their presence in other animals were available. Here we
      report the presence of these SINEs in a wide range of rodents (in all 15 tested
      families) as well as primates and tree-shrews and their absence in other mammals.
      Distribution pattern of these SINEs in mammals supports close relationship
      between rodents and primates as well as tree-shrews. Sequence analysis of these
      elements, apparently descending from cellular 7SL RNA indicates their
      rearrangements such as dimerization (Alu), quasi-dimerization (B1), acquiring a
      tRNA-related unit (B1-dID), extended deletions, etc., preceding their active
      expansion in the genomes. The revealed common pattern of microenvironment of some
      rearrangement hot spots in SINEs (internal duplications and deletions) suggests
      involvement of short direct repeats in the mechanism of such rearrangements. This
      hypothesis allows us to explain short rearrangements in these and other short
      retroposons.

PMID- 14597181
TI  - Molecular cloning, mapping, and functional analysis of the bovine sulfate
      transporter SLC26a2 gene.
AB  - Sulfate is one of the most important macronutrients in cells and the major sulfur
      source in many organisms as well as one of the most abundant anions in the serum.
      As sulfate is a hydrophilic anion, movement across the lipid bilayer is mediated
      by transporters that regulate efflux and influx. Here, we report the molecular
      cloning, mapping, and functional analysis of the bovine solute carrier/sulfate
      transporter SLC26a2 gene, the first member of this family to be cloned in cattle.
      A recombinant phage library was screened, and single phages harbouring the
      SLC26a2 gene was isolated and sequenced. A fragment of 6295 base pairs (bp) of
      the bovine SLC26a2 gene harbouring exon 2 and exon 3 was used for further
      analysis. Similar to the human, ovine, mouse, and rat SLC26a2 gene, the bovine
      ortholog consists of two coding exons. The open reading frame harbours 2202
      nucleotides (nt), coding for a protein of 734 amino acids with a calculated
      molecular weight of 81.5 kilodaltons (kDa) and a statistical isoelectric point
      (pI) of 8.77. The bovine SLC26a2 gene was mapped to chromosome 7q23-q24 (BTA 7q23
      q24) by fluorescence in situ hybridisation (FISH) analysis. Two point mutations
      were identified comparing the DNAs of 300 Holstein Frisian cattle, one of them
      resulting in an isoleucine to serine amino acid exchange at position 520. The
      Ile520Ser exchange influences the sulfate uptake as measured in primary
      fibroblasts isolated from testis and in immortalized fibroblastoid bovine cell
      lines.

PMID- 14597182
TI  - Identification of single nucleotide polymorphisms in the human gamma-glutamyl
      hydrolase gene and characterization of promoter polymorphisms.
AB  - gamma-Glutamyl hydrolase (GGH) plays a central role in folate metabolism and
      antifolate action. Increased GGH activity has been found in rat hepatoma cells
      resistant to the cancer drug methotrexate (MTX). The aim of this study was to
      identify polymorphisms in the GGH gene that modulate GGH activity and that may
      affect methotrexate resistance. Exons of the human gamma-glutamyl hydrolase
      (hGGH) gene were amplified by polymerase chain reaction (PCR) from breast cancer
      tissue and leukemia cell lines. Single-stranded conformational polymorphism
      (SSCP) analysis was performed, and PCR products containing different patterns
      were cloned and sequenced. Six single nucleotide polymorphisms (SNPs) were
      identified, at bases -401C>T, -354G>T, -124T>G, +16T>C, +452C>T, and +1102A>G,
      relative to the A of the translation start codon being considered as +1. The SNP
      at +16, which changes codon -19 (relative to the start of the mature hGGH
      protein) in the endoplasmic reticulum targeting sequence of hGGH protein from
      cysteine to arginine, has previously been identified in this laboratory. The SNP
      at +452 changes the conserved hGGH protein codon 127 from threonine to
      isoleucine. The functions of SNPs in the promoter of the hGGH gene were studied
      by site-directed mutagenesis of a 516-bp region of the hGGH gene promoter in a
      luciferase reporter vector and transfection into HepG2 and MCF-7 cells. All of
      the promoter polymorphisms enhanced the production of luciferase compared to the
      wild-type hGGH gene promoter in HepG2 cells, and -401C>T and -124T>G enhanced
      luciferase expression in MCF-7 cells, suggesting that polymorphisms in the hGGH
      gene promoter may increase expression of hGGH protein.

PMID- 14597183
TI  - Characterization of the mouse lysosomal sialidase promoter.
AB  - Lysosomal sialidase is required for the catabolism of sialoglycoconjugates such
      as gangliosides and deficiency in this enzyme results in the autosomal recessive
      disease sialidosis. Furthermore, we have shown that overexpression of human
      sialidase is sufficient to clear accumulated ganglioside in Tay-Sachs neuroglia
      [Hum. Mol. Genet. 8 (1999) 1111]. In this paper, we have characterized the 5'
      regulatory region of the mouse lysosomal sialidase gene in order to understand
      the molecular mechanisms regulating its expression. We used bioinformatic
      approaches to identify a transcriptional initiation site at -45 bp relative to
      the ATG and significant sequence homology with the rat and human promoters.
      Expression by the promoter was found to be cell-type restricted and required at
      least 750 bp upstream of the ATG for high-level expression. DNAse I footprinting
      analysis and reporter gene assays indicated that the promoter is responsive to Sp
      1. We discovered a CCAAT box and four E-boxes within the mouse upstream region
      and demonstrated that CCAAT displacement protein as well as the muscle regulatory
      factors MyoD and Myf-5 influence sialidase expression. Taken together, these
      results identify cis- and trans-acting factors involved in the regulation of
      sialidase and point to mechanisms of gene upregulation.

PMID- 14597184
TI  - Detection of DNA fragmentation and apoptotic proteins, and quantification of
      uncoupling protein expression by real-time RT-PCR in adipose tissue.
AB  - Better understanding of the mechanisms involved in adipose tissue growth and
      metabolism is critical for the development of more effective treatments for
      obesity. However, because of its high lipid and low protein content, adipose
      tissue can present unique problems in some experimental procedures. We describe
      three protocols that provide new or improved methods for analysis of DNA, RNA,
      and protein from different adipose tissues. The first protocol provides a simple
      and rapid method for separation of fragmented DNA and visualization of apoptotic
      DNA laddering without the need for radioisotopes. This technique allows for an
      estimate of the amount of DNA fragmentation, and hence, apoptosis. The second
      protocol details subcellular fractionation of adipose tissue for the extraction
      of protein in the mitochondrial and cytosol fractions and the measurement of
      apoptotic protein (Bcl-2 and Bax) levels in each fraction. The last protocol
      involves extraction of total RNA from adipose tissue and the measurement of
      uncoupling protein mRNA using real-time RT-PCR, a method that has not previously
      been used to measure expression of uncoupling proteins in adipose tissue.

PMID- 14597185
TI  - A high performance micro-dual-wavelength-spectrophotometer (MDWS).
AB  - The dual wavelength spectrophotometer (DWS) has proven to be the most sensitive
      device to monitor minute optical absorbance changes, which are inaccessible to
      conventional single or double beam spectrophotometers. The typical set ups, e.g.
      extensively used for Ca2+ or phytochrome measurements, are huge, expensive and
      cumbrous. Therefore, a novel high performance micro-dual-wavelength
      spectrophotometer (MDWS) was developed. It is miniaturized and no moving parts
      such as vibrational mirrors or rotating filter wheels involved. Its
      specifications are superior compared to the conventional set up being capable of
      detecting minute optical changes (reflection, absorbance, transmittance) at
      particular wavelengths.

PMID- 14597186
TI  - A new precursor for the immobilization of enzymes inside sol-gel-derived hybrid
      silica nanocomposites containing polysaccharides.
AB  - Tetrakis(2-hydroxyethyl) orthosilicate (THEOS) introduced by Hoffmann et al. (J.
      Phys. Chem. B., 106 (2002) 1528) was first used to prepare hybrid nanocomposites
      containing various polysaccharides and immobilize enzymes in these materials. Two
      different types of O-glycoside hydrolyses (EC3.2.1), 1-->3-beta-D-glucanase LIV
      from marine mollusk Spisula sacchalinensis and alpha-D-galactosidase from marine
      bacterium Pseudoalteromonas sp. KMM 701, were taken for the immobilization. To
      reveal whether the polysaccharide inside the hybrid material influences the
      enzyme entrapment and functioning, negatively charged xanthan, cationic
      derivative of hydroxyethylcellulose and uncharged locust bean gum were examined.
      The mechanical properties of these nanocomposites were characterized by a dynamic
      rheology and their structure by a scanning electron microscopy. It was found that
      1-->3-beta-D-glucanase was usually immobilized without the loss of its activity,
      while the alpha-D-galactosidase activity in the immobilized state depended on the
      polysaccharide type of material. An important point is that the amount of
      immobilized enzymes was small, comparable to their content in the living cells.
      It was shown by the scanning electron microscopy that the hybrid nanocomposites
      are sufficiently porous that allows the enzymatic substrates and products to
      diffuse from an external aqueous solution to the enzymes, whereas protein
      molecules were immobilized firmly and not easily washed out of the silica matrix.
      A sharp increase of the enzyme lifetime (more than a hundred times) was observed
      after the immobilization. As established, the efficient entrapment of enzymes is
      caused by few advantages of new precursor over the currently used TEOS and TMOS:
      (i) organic solvents and catalysts are not needed owing to the complete
      solubility of THEOS in water and the catalytic effect of polysaccharides on the
      sol-gel processes; (ii) the entrapment of enzymes can be performed at any pH
      which is suitable for their structural integrity and functionality; (iii) a gel
      can be prepared at reduced concentrations of THEOS (1-2%) in the initial solution
      that excludes a notable heat release in the course of its hydrolysis.

PMID- 14597188
TI  - Quantitative determination of carbon monoxide in cell culture supernatants by
      spectrophotometric analysis.
AB  - A simple, sensitive, nonradioactive method for measuring carbon monoxide (CO) in
      cell culture supernatant is described. Dissolved CO reacts with hemoglobin (Hb)
      to carboxyhemoglobin (HbCO) in a modified Conway cell. HbCO is quantified by
      spectrophotometric analysis, and total concentration of CO given in microg CO/l
      cell culture supernatant is mathematically calculated. Furthermore, we compared
      our newly developed method with a recently published method. Confluent human
      umbilical vein epithelial cells (HUVEC) were incubated with 10(-6) M
      hydrocortisone known to induce heme oxygenase-2 protein and transcript expression
      for 4 h and CO production was measured. Levels following hydrocortisone treatment
      were significantly enhanced compared to controls when using our newly developed
      technique (p<0.05), whereas only a nonsignificant trend could be observed using
      the recently published method. We conclude that this nonradioactive technique to
      quantify CO is more sensitive than previous ones, thereby allowing to measure
      even physiologic quantities of CO in aqueous solutions.

PMID- 14597187
TI  - Rapid analysis of protein-nucleic acid complexes using MALDI TOF mass
      spectrometry and ion pair reverse phase liquid chromatography.
AB  - The RuvABC resolvasome of Escherichia coli typifies nucleoprotein complexes
      involved in genetic transactions. This molecular assembly catalyses the
      resolution of Holliday junctions that arise during genetic recombination and DNA
      repair. This process involves two key steps: branch migration, catalysed by the
      RuvB protein that is targeted to the Holliday junction by the structure specific
      RuvA protein, and resolution, which is catalysed by the RuvC endonuclease. We
      have used matrix-assisted laser desorption/ionisation time of flight mass
      spectrometry (MALDI-TOF MS) to rapidly identify the binding of RuvA to an
      immobilised synthetic Holliday junction; unambiguous identification was verified
      using tryptic digest of the bound protein. In conjunction with a novel
      fluorescent-based technique incorporating ion pair reverse phase liquid
      chromatography, a "footprint" of the RuvA:Holliday complex was obtained. These
      two complementary techniques offer a generic approach to the analysis of
      nucleoprotein complexes.

PMID- 14597189
TI  - Exploring the mechanism of competence development in Escherichia coli using
      quantum dots as fluorescent probes.
AB  - The mechanism of divalent Ca2+ cation induction of Escherichia coli competence is
      still not fully understood, though it is a common method for introducing
      recombinant DNA into bacterial cells in gene engineering. Quantum dots (QDs), as
      a new fluorescent probe of being applied in biology research, have aroused great
      interest. In this paper, we explored the mechanism of E. coli competence
      development using QDs for the first time. Results showed that water-soluble QDs
      of diameter 3-4 nm could go into competent cells, but could not enter
      noncompetent cells. This result was further confirmed using atomic force
      microscopy and DNA transforming experiments, suggesting that nonphysiological,
      high concentrations of Ca2+ enhanced the penetrability of cell membranes so that
      QDs, which cannot enter cells normally due to their greater diameter (3-4 nm),
      can do so easily into competent cells. Therefore, we believe that, at least for
      E. coli, the mechanism of Ca2+-induced competence development is mediated
      physicochemically rather than physiologically.

PMID- 14597191
TI  - A sensitive radiometric assay to measure D-xylulose kinase activity.
AB  - A radiometric test system for D-xylulose kinase (XK) was developed for the
      measurement of enzyme activity in crude cell extracts and to minimize the volume
      of reaction mixtures besides increasing the sensitivity. [U-14C]xylulose 5
      phosphate was produced from commercially available [U-14C]xylose in a coupled
      assay system containing D-xylose isomerase, which yields [U-14C]xylulose, the
      substrate of ATP-dependent D-xylulose kinase. Separation of products and
      substrates was achieved by thin layer chromatography, identification of
      radioactive spots by radioscanning followed by quantitative scintillation
      counting. The protocol was validated through determination of kinetic constants
      of a purified His-tagged enzyme from Escherichia coli and comparison with the
      spectrophotometric method. The radiometric assay was applied to determine
      xylulose kinase activity in crude cell extracts from a variety of eukaryotic and
      prokaryotic organisms.

PMID- 14597190
TI  - Reduced nonspecific adsorption on covalently immobilized protein surfaces using
      poly(ethylene oxide) containing blocking agents.
AB  - In a number of applications, e.g. DNA/protein micro-array technology, enzyme
      linked immunosorbent assay (ELISA) technology or surface plasmon resonance (SPR)
      technology, the covalent coupling of proteins to surfaces is required. Following
      the covalent coupling of proteins, the remaining reactive groups should be
      blocked in order to avoid covalent binding of the analyte to the reactive
      surface. To this end, preferably blocking agents containing groups that avoid
      nonspecific adsorption should be used. These blocking agents are typically
      ethanolamine and cysteine for protein coupling via amino groups and thiol groups,
      respectively. This report presents novel blocking agents containing poly(ethylene
      oxide) (PEO) groups. These blocking agents show enhanced qualities to avoid
      nonspecific adsorption and can therefore have advantages in versatile protein
      surface technologies.

PMID- 14597192
TI  - A novel immunohistochemical method for evaluation of antibody specificity and
      detection of labile targets in biological tissue.
AB  - Immunohistochemistry is a key tool for analyzing target molecule localization
      within tissues. However, accurate results require an antibody that can
      distinguish between similar compounds. We present a simple immunohistochemical
      method that can also be used to rapidly evaluate antibodies' specificities. We
      demonstrate this technique with serotonin, an extremely labile compound.
      Serotonin (5-hydroxytryptamine, 5HT) is an important neurotransmitter regulating
      normal cognition and several mental disorders, as well as tumor growth,
      cardiopathology, and embryogenesis. Immunohistochemical detection of serotonin is
      commonly used as a neuronal cell marker and to provide crucial information on
      serotonin's role as an embryonic morphogen. It is necessary to be able to
      distinguish serotonin from closely related molecules with significantly different
      biological activity. Using our method, we identify antibodies that are specific
      for serotonin and show that some commercial 5HT antibodies often used to identify
      serotonergic cells in published papers are not 5HT-specific. These data
      demonstrate the necessity of specifically testing antibodies (especially in areas
      of high clinical relevance such as 5HT). We also illustrate detection of
      serotonergic cells in embryonic tissue using our technique. This method offers a
      number of general advantages for testing specificity of antibodies to any
      biological molecule, and helps avoid false positives and negatives during
      immunohistochemistry.

PMID- 14597193
TI  - MAP kinases in chondrocyte differentiation.
AB  - The majority of the vertebrate skeleton develops through the process of
      endochondral ossification and involves successive steps of chondrogenesis,
      chondrocyte proliferation, and hypertrophic chondrocyte differentiation.
      Interruption of this program through gene mutations and hormonal or environmental
      factors contributes to numerous diseases, including growth disorders and
      chondrodysplasias. While a large number of growth factors and hormones have been
      implicated in the regulation of chondrocyte biology, relatively little is known
      about the intracellular signaling pathways involved. Recent data provide novel
      insights into the mechanisms governing acquisition of new phenotypes within the
      chondrogenic program and suggest multiple pivotal roles for members of the
      mitogen-activated protein kinase family and their downstream targets in cartilage
      development. These data are summarized and discussed here.

PMID- 14597194
TI  - Both neural crest and placode contribute to the ciliary ganglion and oculomotor
      nerve.
AB  - The chick ciliary ganglion is a neural crest-derived parasympathetic ganglion
      that innervates the eye. Here, we examine its axial level of origin and
      developmental relationship to other ganglia and nerves of the head. Using small,
      focal injections of DiI, we show that neural crest cells arising from both the
      caudal half of the midbrain and the rostral hindbrain contribute to the ciliary
      as well as the trigeminal ganglion. Precursors to both ganglia have overlapping
      migration patterns, moving first ventrolaterally and then rostrally toward the
      optic vesicle. At the level of the midbrain/forebrain junction, precursors to the
      ciliary ganglion separate from the main migratory stream, turn ventromedially,
      and condense in the vicinity of the rostral aorta and Rathke's pouch. Ciliary
      neuroblasts first exit the cell cycle at early E2, prior to and during ganglionic
      condensation, and neurogenesis continues through E5.5. By E3, markers of neuronal
      differentiation begin to appear in this population. By labeling the ectoderm with
      DiI, we discovered a new placode, caudal to the eye and possibly contiguous to
      the trigeminal placode, that contributes a few early differentiating neurons to
      the ciliary ganglion, oculomotor nerve, and connecting branches to the ophthalmic
      nerve. These results suggest for the first time a dual neural crest and placodal
      contribution to the ciliary ganglion and associated nerves.

PMID- 14597195
TI  - Efficient gene delivery and gene expression in zebrafish using the Sleeping
      Beauty transposon.
AB  - We used the Tc1/mariner family transposable element Sleeping Beauty (SB) for
      transgenesis and long-term expression studies in the zebrafish (Danio rerio), a
      popular organism for clinical disease, vertebrate patterning, and cell biology
      applications. SB transposase enhanced the transgenesis and expression rate
      sixfold (from 5 to 31%) and more than doubled the total number of tagged
      chromosomes over standard, plasmid injection-based transgenesis methods.
      Molecular analysis of these loci demonstrated a precise integration of these
      elements into recipient chromosomes with genetic footprints diagnostic of
      transposition. GFP expression from transposase-mediated integrants was Mendelian
      through the eighth generation. A blue-shifted GFP variant (BFP) and a red
      fluorescent protein (DsRed) were also useful transgenesis markers, indicating
      that multiple reporters are practical for use with SB in zebrafish. We showed
      that SB is suitable for tissue-specific transgene applications using an
      abbreviated gamma-crystallin GFP cassette. Finally, we describe a general utility
      transposon vector for chromosomal engineering and molecular genetics experiments
      in zebrafish. Together, these data indicate that SB is an efficient tool for
      transgenesis and expression in zebrafish, and that the transposon will be useful
      for gene expression in cell biology applications as well as an insertional
      mutagen for gene discovery during development.

PMID- 14597196
TI  - Overexpression of Sonic Hedgehog suppresses embryonic hair follicle
      morphogenesis.
AB  - The Sonic Hedgehog (Shh) signalling pathway plays a central role in the
      development of the skin and hair follicle and is a major determinant of skin
      tumorigenesis, most notably of basal cell carcinoma (BCC). Various mouse models
      involving either ablation or overexpression of key members of the Shh signalling
      pathway display a range of skin tumours. To further examine the role of Shh in
      skin development, we have overexpressed Shh in a subset of interfollicular basal
      cells from 12.5 dpc under the control of the human keratin 1 (HK1) promoter. The
      HK1-Shh transgenic mice display a range of skin anomalies, including highly
      pigmented inguinal lesions and regions of alopecia. The most striking hair
      follicle phenotype is a suppression in embryonic follicle development between
      14.0 and 19.0 dpc, resulting in a complete absence of guard, awl, and auchene
      hair fibres. These data indicate that alternative signals are responsible for the
      development of different hair follicles and point to a major role of Shh
      signalling in the morphogenesis of guard, awl, and auchene hair fibres. Through a
      comparison with other mouse models, the characteristics of the HK1-Shh transgenic
      mice suggest that the precise timing and site of Shh expression are key in
      dictating the resultant skin and tumour phenotype.

PMID- 14597198
TI  - The MAPK cascade in equally cleaving spiralian embryos.
AB  - Spiralian development is shared by several protostome phyla and characterized by
      regularities in early cleavage, fate map, and larva. Experimental evidence from
      multiple spiralian species implicates cells in the D quadrant lineage as the
      organizer of future axial development of the embryo. However, the mechanisms by
      which the D quadrant is specified differ between species with equal and unequal
      spiral cleavage. Equally cleaving mollusc embryos establish the D quadrant via
      cell-cell interactions between the micromeres and macromeres at the 24- to 36
      cell stage. In unequally cleaving embryos, the D quadrant is established at the 4
      cell stage via asymmetries in the first 2 cell divisions. We have begun to
      explore the molecular mechanisms of D quadrant patterning in spiralians.
      Previously, we showed that, in the unequally cleaving embryo of the mollusc
      Ilyanassa obsoleta, the MAPK pathway is activated and functionally required in 3D
      and also in the micromeres known to require a signal from 3D. Here, we examine
      the role of MAPK signaling in 4 spiralians with equal cleavage. In 3 equally
      cleaving molluscs, the chiton Chaetopleura, the limpet Tectura, and the snail
      Lymnaea, the MAPK pathway is activated in the 3D cell but not in the overlying
      micromeres. In the equally cleaving embryo of the polychaete annelid Hydroides,
      MAPK activation was not detected in the 3D macromere but was observed in one of
      its daughter cells, 4d. In addition, inhibiting Tectura MAPK activation disrupts
      differentiation of 3D and cells induced by it, supporting a functional role for
      MAPK in axis specification in equally cleaving spiralians. Thus, MAPK signaling
      may have a conserved role in the D quadrant organizer cell 3D in molluscs.
      However, there have been at least 2 evolutionary changes in the activation of the
      MAPK pathway during spiralian evolution. MAPK function in the Ilyanassa
      micromeres is a recent cooption and, since the divergence of annelids and
      molluscs, there has been a shift in onset of MAPK activation between 3D and 4d.
      We propose that this latter shift correlates with a change in the timing of
      specification of the secondary embryonic axis.

PMID- 14597200
TI  - Stem cell and niche development in the postnatal rat testis.
AB  - Adult tissue stem cells self-renew and differentiate in a way that exactly meets
      the biological demand of the dependent tissue. We evaluated spermatogonial stem
      cell (SSC) activity in the developing rat testis and the quality and
      accessibility of the stem cell niche in wild type, and two busulfan-treated
      models of rat pup recipient testes using an SSC transplantation technique as a
      functional assay. While our results revealed a 69-fold increase in stem cell
      activity during rat testis development from neonate to adult, only moderate
      changes in SSC concentration were observed, and stem cells from neonate, pup, and
      adult donor testes produce spermatogenic colonies of similar size. Analysis of
      the stem cell niche in recipient rat testes demonstrated that pup testes support
      high levels of donor stem cell engraftment when endogenous germ cells are removed
      or compromised by busulfan treatment. Fertility was established when rat pup
      donor testis cells were transplanted into fetal- or pup-busulfan-treated
      recipient rat pup testes, and the donor genotype was transmitted to subsequent
      generations. These results provide insight into stem cell/niche interactions in
      the rat testis and demonstrate that techniques originally developed in mice can
      be extended to other species for regenerative medicine and germline modification.

PMID- 14597199
TI  - cki-1 links cell division and cell fate acquisition in the C. elegans somatic
      gonad.
AB  - The formation of a complex multicellular organism requires the precise
      specification of many diverse cell types at the correct time and position
      throughout development. This may be achieved by coordinating cell fate
      specification processes with progression through the cell cycle. Here, we show
      that the extra distal tip cells (DTCs) associated with the loss of cki-1, a
      Caenorhabditis elegans homologue of the cyclin-dependent kinase inhibitor p27, do
      not arise from duplications of pre-existing DTCs, but that they are formed from
      another cell type within the somatic gonad. Results from our laser microsurgery
      experiments suggest that the extra DTCs are caused by aberrant somatic gonadal
      precursor cell divisions in the absence of cki-1, resulting in abnormal daughter
      cell fates. cki-1(RNAi) animals also possess extra anchor cells and ectopic gonad
      arms with variable sheath cell numbers and positioning. In addition, cki-1(RNAi)
      animals display an endomitotic oocyte (Emo) phenotype. Our results uncover a
      novel role of this CKI in cell fate acquisition, either by directly influencing
      specification, or through a more conventional role in appropriately linking cell
      cycle phase with this process.

PMID- 14597197
TI  - Brain-derived neurotrophic factor signal enhances and maintains the expression of
      AMPA receptor-associated PDZ proteins in developing cortical neurons.
AB  - Postsynaptic molecules with PDZ domains (PDZ proteins) interact with various
      glutamate receptors and regulate their subcellular trafficking and stability. In
      rat neocortical development, the protein expression of AMPA-type glutamate
      receptor GluR1 lagged behind its mRNA expression and rather paralleled an
      increase in PDZ protein levels. One of the neurotrophins, brain-derived
      neurotrophic factor (BDNF), appeared to contribute to this process, regulating
      the PDZ protein expression. In neocortical cultures, BDNF treatment upregulated
      SAP97, GRIP1, and Pick1 PDZ proteins. Conversely, BDNF gene targeting
      downregulated these same PDZ molecules. The BDNF-triggered increases in PDZ
      proteins resulted in the elevation of their total association with the AMPA
      receptors GluR1 and GluR2/3, which led to the increase in AMPA receptor proteins.
      When Sindbis viruses carrying GluR1 or GluR2 C-terminal decoys disrupted their
      interactions, GluR2 C-terminal decoys inhibited both BDNF-triggered GluR1 and
      GluR2/3 increases, whereas GluR1 C-terminal decoys blocked only the BDNF
      triggered GluR1 increase. In agreement, coexpression of SAP97 and GluR1 in
      nonneuronal HEK293 cells increased both proteins compared with their single
      transfection, implying mutual stabilization. This work reveals a novel function
      of BDNF in postsynaptic development by regulating the PDZ protein expression.

PMID- 14597201
TI  - The catalytic domain of xPAK1 is sufficient to induce myosin II dependent in vivo
      cell fragmentation independently of other apoptotic events.
AB  - During apoptosis, cells are fragmented into sealed packages for safe disposal by
      phagocytosis, a process requiring major reorganisation of the cytoskeleton. The
      small p21 GTPase-activated kinases (PAKs) have been implicated in regulating
      cytoskeletal dynamics and a subset are activated by caspase 3/7 cleavage.
      However, the functional importance of this activation in apoptosis remains
      unknown. Using early Xenopus embryos, we have dissected xPAK1 activation from
      other causative events in apoptosis. An apoptotic-like cell fragmentation was
      observed 30 min after expression of the xPAK1 catalytic domain and occurred in
      the absence of other markers of apoptosis. In vitro, activated xPAK1
      phosphorylated the regulatory light chain (xMLC) of myosin II at threonine 18 and
      serine 19, events known to activate the actin-dependent ATPase of cytoskeletal
      myosin. In vivo, activated xPAK1 induced hyperphosphorylation of xMLC. BDM, a
      myosin inhibitor, and ML-7, a MLCK inhibitor, both abrogated cell fragmentation
      induced by activated xPAK1, and ML-7 also inhibited xPAK1 activity. Endogenous
      xPAK1 was cleaved during normal apoptosis and this was associated with xPAK1
      activation and increased serine 19 phosphorylation of xMLC. The data show that
      PAK activation is sufficient for apoptotic body formation in vivo and strongly
      suggest that activation of myosin II is essential for this process.

PMID- 14597202
TI  - The odd-skipped family of zinc finger genes promotes Drosophila leg segmentation.
AB  - Notch signaling controls formation of joints at leg segment borders and growth of
      the developing Drosophila leg. Here, we identify the odd-skipped gene family as a
      key group of genes that function downstream of the Notch receptor to promote
      morphological changes associated with joint formation during leg development.
      odd, sob, drm, and bowl are expressed in a segmental pattern in the developing
      leg, and their expression is regulated by Notch signaling. Ectopic expression of
      odd, sob, or drm can induce invaginations in the leg disc epithelium and
      morphological changes in the adult leg that are characteristic of endogenous
      invaginating joint cells. These effects are not due to an alteration in the
      expression of other genes of the developing joint. While odd or drm mutant clones
      do not affect leg segmentation, and thus appear to act redundantly, bowl mutant
      clones do perturb leg development. Specifically, bowl mutant clones result in a
      failure of joint formation from the distal tibia to tarsal segment 5, while more
      proximal clones cause melanotic protrusions from the leg cuticle. Together, these
      results indicate that the odd-skipped family of genes mediates Notch function
      during leg development by promoting a specific aspect of joint formation, an
      epithelial invagination. As the odd-skipped family genes are involved in
      regulating cellular morphogenesis during both embryonic segmentation and hindgut
      development, we suggest that they may be required in multiple developmental
      contexts to induce epithelial cellular changes.

PMID- 14597203
TI  - Characterization of Brachyury genes in the dogfish S. canicula and the lamprey L.
      fluviatilis. Insights into gastrulation in a chondrichthyan.
AB  - In order to gain insights into the evolution of gastrulation mechanisms among
      vertebrates, we have characterized a Brachyury-related gene in a lamprey,
      Lampetra fluviatilis, and in a chondrichthyan, Scyliorhinus canicula. These two
      genes, respectively termed LfT and ScT, share with their osteichthyan
      counterparts prominent expression sites in the developing notochord, the tailbud,
      but also a transient expression in the prechordal plate, which is likely to be
      ancestral among vertebrates. In addition, the lamprey LfT gene is transcribed in
      the endoderm of the pharyngeal arches and the epiphysis, two expression sites
      that have not been reported thus far in gnathostomes, and, as in the chick, in
      the differentiating nephrotomes. Since Brachyury expression in nascent mesoderm
      and endoderm is highly conserved among vertebrates as well as cephalochordates,
      we have used this marker to identify these cell populations during gastrulation
      in the dogfish. The results suggest that these cells are initially present over
      the whole margin of the blastoderm and are displaced during gastrulation to its
      posterior part, which may correspond to the site of mesoderm and endoderm
      internalization. These data provide the first molecular characterization of
      gastrulation in a chondrichthyan. They indicate that gastrulation in the dogfish
      and in some amniotes shares striking similarities despite the phylogenetic
      distance between these species. This supports the hypothesis that the extensively
      divergent morphologies of gastrulae among vertebrates largely result from
      adaptations to the presence of yolk.

PMID- 14597204
TI  - The novel ankyrin-repeat containing kinase ARCK-1 acts as a suppressor of the
      Spalten signaling pathway during Dictyostelium development.
AB  - Spalten (Spn), a member of the PP2C family of Ser/Thr protein phosphatases, is
      required for Dictyostelium cell-type differentiation and morphogenesis. We have
      identified a new protein kinase, ARCK-1, through a second site suppressor screen
      for mutants that allow spn null cells to proceed further through development.
      ARCK-1 has a C-terminal kinase domain most closely related to Ser/Thr protein
      kinases and an N-terminal putative regulatory domain with ankyrin repeats, a 14-3
      3 binding domain, and a C1 domain, which is required for binding to RasBGTP in a
      two-hybrid assay. Disruption of the gene encoding ARCK-1 results in weak, late
      developmental defects. However, overexpression of ARCK-1 phenocopies the spn null
      phenotype, consistent with Spn and ARCK-1 being on the same developmental
      pathway. Our previous analyses of Spn and the present analysis of ARCK-1 suggest
      a model in which Spn and ARCK-1 differentially control the phosphorylation state
      of a protein that regulates cell-type differentiation. Dephosphorylation of the
      substrate by Spn is required for cell-type differentiation. Control of ARCK-1 and
      Spn activities by upstream signals is proposed to be part of the developmental
      regulatory program mediating cell-fate decisions in Dictyostelium.

PMID- 14597205
TI  - A transcriptional chain linking eye specification to terminal determination of
      cone cells in the Drosophila eye.
AB  - Lozenge (Lz) is a multifunctional transcription factor that is activated in a
      pool of pluripotent cells at the beginning of a wave of morphogenesis during
      Drosophila eye development. Lozenge belongs to the Runx class of transcription
      factors that includes the mammalian proteins AML1, Runx 2, and Runx 3. These
      proteins allow a tissue-specific precursor population of cells to attain multiple
      terminally differentiated fates. We investigated the transcriptional control of
      lz to determine the mechanism by which precursor populations achieve their
      identity. We have identified a 251-bp region in the second intron of the lz gene
      that functions as a minimal eye-specific enhancer. We provide evidence that Sine
      oculis and Glass are the two major activators of Lz expression during eye
      development. This work establishes a bridge between early eye specification genes
      and late cell-specific transcription factors required for terminal determination
      of cone cells in the eye.

PMID- 14597206
TI  - mua-6, a gene required for tissue integrity in Caenorhabditis elegans, encodes a
      cytoplasmic intermediate filament.
AB  - Locomotion in Caenorhabditis elegans requires force transmission through a
      network of proteins linking the skeletal muscle, via an intervening basal lamina
      and epidermis (hypodermis), to the cuticle. Mutations in mua-6 result in
      hypodermal rupture, muscle detachment from the bodywall, and progressive
      paralysis. It is shown that mua-6 encodes the cytoplasmic intermediate filament
      (cIF) A2 protein and that a MUA-6/IFA-2::GFP fusion protein that rescues the
      presumptive mua-6 null allele localizes to hypodermal hemidesmosomes. This result
      is consistent with what is known about the function of cIFs in vertebrates.
      Although MUA-6/IFA-2 is expressed embryonically, and plays an essential
      postembryonic role in tissue integrity, it is not required for embryonic
      development of muscle-cuticle linkages nor for the localization of other cIFs or
      hemidesmosome-associated proteins in the embryo. Finally, the molecular lesion in
      the mua-6(rh85) allele suggests that the head domain of the MUA-6/IFA-2 is
      dispensable for its function.

PMID- 14597207
TI  - Long-range, nonautonomous effects of activated Notch1 on tissue homeostasis in
      the nail.
AB  - Using an antibody directed against gamma-secretase-generated antigen unique to
      activated Notch1, we mapped Notch1 activation strictly to suprabasal cells in
      epidermis, nail matrix, and other skin appendages during normal development. The
      consequences of Notch1 activation in keratinizing nail cells were investigated in
      a transgenic mouse model. Ectopic activation of Notch1 in postmitotic cells
      within the nail keratogenous zone resulted in longer nails. BrdU labeling
      revealed an increased number of mitotic cells in transgenic nails. The matrix and
      keratogenous zone expanded distally due to the increase in cell numbers. The
      mitosis-promoting effects by a gene product expressed exclusively in postmitotic
      cells indicates a long-range effect of transgenic Notch1 on regulation of nail
      homeostasis. We demonstrate that activation of Notch1 in the keratogenous zone
      resulted in ectopic activation of Wnt signaling, the first such evidence in
      vertebrates. However, we detected little or no beta-catenin activation in
      proliferating matrix cells, indicating that Wnt is at most an indirect mediator
      of Notch-induced proliferation. These data support the existence of a novel, cell
      nonautonomous role for Notch in maintaining homeostasis of stratified squamous
      epithelia by indirectly promoting mitosis in basally located cells.

PMID- 14597208
TI  - Na+, K+, ATPase activity in the human and bovine preimplantation embryo.
AB  - Blastocyst formation is associated with a marked increase in ATP production, much
      of which is thought to be associated with the active transport of ions across the
      trophectoderm mediated by the sodium pump (Na+, K+, ATPase) resulting in the
      vectorial transport of water into the blastocoel. In this study, the biochemical
      activity of the sodium pump was measured directly in single human and bovine
      embryo extracts by monitoring the conversion of ATP to ADP in the presence and
      absence of ouabain. ATP and ADP were assayed by HPLC. In both species, there was
      a transient, significant increase in sodium pump activity while the blastocyst
      was actively expanding. The oxygen consumption of single human blastocysts was
      measured in order to estimate the proportion of total ATP used by the Na+, K+,
      ATPase. The results suggest that approximately 60 and 36% of the ATP produced is
      used by the sodium pump during blastocoel expansion in the human and bovine
      blastocyst, respectively.

PMID- 14597209
TI  - Update on primary immunodeficiency: defects of lymphocytes.
AB  - The recent identification of the genes involved in many primary immunodeficiency
      disorders has led to a significant increase in our understanding of the
      pathogenesis of these defects. Many of these disorders share a clinical phenotype
      with common features such as recurrent infections, chronic inflammation, and
      autoimmunity. Although some of these immune defects have mild presentations and
      better outcomes, others result in severe infections and significant morbidity and
      mortality. For these, early diagnosis and treatment are critical. This review
      provides an overview of the genetic defects and clinical features of primary
      immune deficiencies due to defects in lymphocytes.

PMID- 14597210
TI  - Non-Hodgkin's B cell lymphoma in persons with acquired immunodeficiency syndrome
      is associated with increased serum levels of IL10, or the IL10 promoter -592 C/C
      genotype.
AB  - Interleukin-10 (IL10) may contribute to the development of non-Hodgkin's B cell
      lymphoma, especially in the context of acquired immunodeficiency syndrome (AIDS),
      where lymphoma incidence is greatly increased. Utilizing specimens from the
      Multicenter AIDS Cohort Study (MACS) obtained prior to diagnosis of AIDS
      associated lymphoma, detectable serum human IL10 was seen much more frequently in
      lymphoma cases (n = 61, 26%) compared to CD4-matched AIDS controls (5%, P =
      0.004), or to HIV-infected (2%, P = 0.002) or HIV uninfected subjects (0%, P =
      0.0003). In longitudinal studies, detectable IL10 occurred at times closest to
      but preceding lymphoma diagnosis (P = 0.01). In an independent genetic analysis
      of single-nucleotide polymorphisms within the promoter region of the IL10 gene in
      1157 MACS subjects, a high IL10-expressing genotype (-592 C/C) was
      overrepresented among lymphoma subjects (P = 0.009), even when controlling for
      race (P = 0.006). These results suggest that elevated serum IL10 or the IL10
      promoter -592 C/C genotype are associated with development of AIDS lymphoma.

PMID- 14597211
TI  - Intraindividual reproducibility of nasal allergic responses to diesel exhaust
      particles indicates a susceptible phenotype.
AB  - Previous research indicates that diesel exhaust particles (DEP) can augment
      allergen- driven allergic responses. In vivo nasal challenge offers a practical
      method to characterize variation in response to pulmonary toxicants and
      immunogens. We investigated the reproducibility of responses to determine whether
      susceptibility to DEP's adjuvant effects is intrinsic or extrinsic. Eighteen
      nonsmoking rhinitic volunteers with positive skin tests to ragweed were randomly
      assigned to allergen/placebo or allergen + DEP nasal challenge; after 30 days,
      the other "arm" was completed. We replicated the procedure 30 days later. Nasal
      washes were performed after challenge, and allergen-specific IgE and cytokines
      were measured by ELISA. Repeated challenge with allergen+DEP, but not
      allergen/placebo, produced reproducible responses for IgE, IL-4, and INF-gamma.
      DEPs ability to enhance allergic responses was highly reproducible within
      individuals and was independent from response to allergen, suggesting that
      susceptibility to DEPs adjuvant effects is an intrinsic trait that can be
      quantified using combined allergen + DEP challenges.

PMID- 14597212
TI  - B lymphocytes from individuals with common variable immunodeficiency respond to B
      lymphocyte stimulator (BLyS protein) in vitro.
AB  - B lymphocyte stimulator (BLyS protein) is a member of the human TNF family of
      ligands. BLyS induces B-lymphocyte proliferation and Ig secretion in vitro and in
      vivo. These qualities suggest that it may be useful as a therapeutic in the
      treatment of immunodeficiencies characterized by low or absent serum
      immunoglobulin, such as common variable immunodeficiency (CVID). CVID is
      characterized by the inability to generate adequate serum Ig despite normal or
      slightly depressed peripheral B, T, and myeloid cell populations. We tested the
      ability of BLyS to stimulate B lymphocytes obtained from CVID patients. Among
      five patients studied, 60% (three of five) produced normal quantities of IgM when
      cultured in the presence of BLyS. B-cell proliferation among patients was
      comparable, with 60% (three of five) responding to BLyS stimulation. These
      results suggest that BLyS induces proliferative and Ig-secretory responses in B
      lymphocytes isolated from some CVID patients and lend support to its potential
      use in therapy of this disorder.

PMID- 14597213
TI  - Fas Ligand-dependent and -independent mechanisms of toxicity induced by T cell
      lymphomas in lymphoid organs and in the liver.
AB  - In the current study, we investigated the effect of growth of FasL(+) tumors in
      vivo on the functions of peripheral lymphoid organs and the liver. Injection of
      FasL(+) LSA tumor cells into syngeneic C57BL/6 wild-type mice but not C57BL/6
      lpr/lpr (Fas-deficient) mice caused apoptosis in splenocytes. Spleen cells
      expressing CD3, CD4, CD8, CD19, Mac-3, and CD44 were all susceptible to tumor
      induced apoptosis. Also, activated T cells were more sensitive to apoptosis
      induced by LSA tumor cell lysate when compared to naive T cells. In contrast,
      anti-Fas Abs (Jo2) induced apoptosis in only activated but not naive T cells.
      When the LSA tumor-bearing mice were injected with a superantigen (SEA), these
      mice showed a significant decrease in the expansion of SEA-reactive Vbeta3(+) and
      Vbeta11(+) T cells. When injected into syngeneic mice, the FasL(+) LSA tumor
      cells caused hepatotoxicity, as indicated by an increase in serum aspartate
      aminotransferase (AST) levels. Interestingly, Fas-deficient C57BL/6 lpr/lpr mice
      also showed significant AST levels in the serum following LSA tumor growth.
      Moreover, hepatocytes isolated from C57BL/6 wild-type and C57BL/6 lpr/lpr mice
      were equally susceptible to apoptosis induced by LSA tumor cell lysate in vitro.
      Using cDNA array, LSA tumor cells were found to express several cytokine genes
      including IL-2, IL-7, IL-11, IL-13, IL-16, lymphotoxin beta, and tumor necrosis
      factor beta. Together, these data suggested that, in mice bearing FasL(+) LSA
      tumor, the immunotoxicity is FasL-based, whereas the hepatotoxicity, at least in
      part, may be FasL-independent.

PMID- 14597214
TI  - Identification of the B-cell epitopes of the early endosome antigen 1 (EEA1).
AB  - Early endosome antigen 1 (EEA1) is a target autoantigen in patients diagnosed
      with neurological and other autoimmune conditions. Eighteen of 65 sera (28%) that
      displayed a vesicular cytoplasmic staining pattern also immunoprecipitated the
      recombinant EEA1. These 18 sera were selected for further clinical, serological
      and epitope mapping studies. Thirty-six percent of the 18 patients had
      neurological diseases. Seventeen sera (94%) reacted with the partial length EEA1
      constructs that included the C-terminal zinc finger (+FYVE) and the methyl
      accepting domain (LeuMA: amino acids 82-1411) in an addressable laser bead assay
      suggesting that the assay may be used for rapid laboratory detection of anti-EEA1
      antibodies. Three of seven sera selected for epitope mapping studies bound to
      EEA1 peptides represented by amino acids 1096-1125, and two reacted with peptides
      represented by amino acids 1296-1320. One serum reacted only with the C-terminal
      peptide 1096-1125. The remaining serum reacted with other EEA1 epitopes. This
      data was supported by the observations that all the sera immunoprecipitated the C
      terminal +FYVE (EEA1 1064-1411) construct, a peptide that also contained the
      linear epitopes 1096-1140. The limited epitope mapping studies suggest that the
      sera from patients with non-neurological diseases recognized epitopes in the
      central and C-terminal EEA1 domains, whereas the patients with neurological
      disease recognized a more restricted set of epitopes in the C-terminal.

PMID- 14597215
TI  - IgM and IgG autoantibodies from microscopic polyangiitis patients but not those
      with other small- and medium-sized vessel vasculitides recognize multiple
      endothelial cell antigens.
AB  - Using a quantitative immunoblotting technique on extracts of macrovascular and
      microvascular endothelial cells (EC), we analyzed serum IgM and IgG reactivities
      of patients with active disease fulfilling the ACR and Chapel Hill criteria for
      the diagnosis of polyarteritis nodosa (PAN) (n = 8), PAN related to hepatitis B
      virus (HBV) infection (HBV-PAN) (n = 5), Wegener's granulomatosis (n = 6),
      microscopic polyangiitis (MPA) (n = 18), Churg-Strauss syndrome (n = 8), and
      patients with chronic HBV infection without PAN (n = 5) and age- and gender
      matched healthy individuals (n = 45). MPA patients' IgM bound to 200-, 105-, 80-,
      65-, 45-, 35-, and 33-kDa major bands, whereas IgM from controls and other
      patients bound predominantly to the 65-kDa band in EC extracts. MPA patients' IgG
      reacted mainly with 105-, 70-, 55-, and 38-kDa protein bands, whereas IgG from
      controls and other patients did not. Our results provide evidence that IgM and to
      a lesser degree IgG from MPA patients specifically recognize multiple EC
      antigens.

PMID- 14597216
TI  - No detrimental effect from chronic exposure to buprenorphine on corticosteroid
      binding globulin and corticosensitive immune parameters.
AB  - Opioid drugs reportedly regulate the immune system via their effects on the
      hypothalamic- pituitary-adrenal (HPA) axis. The present study was carried out to
      assess the effects of chronic exposure to buprenorphine on HPA axis activation,
      corticosteroid-binding globulin (CBG), the main glucocorticoid (GC) carrier, and
      the immune system. Results show that buprenorphine, delivered by osmotic pump
      subcutaneously in C57BL/6 male mice during a 10-day period, caused a marked
      decrease in total corticosterone (CORT) levels at day 1 of exposure. CORT levels
      then increased with maximal values observed at day 5 of exposure. After day 5,
      total CORT levels gradually decreased and returned to control values. No
      significant changes were observed in CBG protein levels and mRNA expression in
      the liver. Since CBG levels remained unchanged, the percentage of free CORT
      values in buprenorphine mice did not differ from control values. Thus, the
      variations observed in the amount of free CORT were related only to changes
      measured in total CORT. These endocrine changes did not have a significant impact
      on the immune parameters measured. Total CD(4)+ and CD(8)+ splenic and thymic
      populations were not modulated by buprenorphine. However, splenocytes from mice
      exposed to buprenorphine after 5 days exhibited greater proliferation upon anti
      TCR monoclonal antibody stimulation than saline-exposed mice. These results
      indicate that buprenorphine can be safely used because it did not have
      significant effects on GC availability for immune corticosensitive cells.

PMID- 14597217
TI  - Identification of natural antibodies to interleukin-18 in the sera of normal
      humans and three nonhuman primate species.
AB  - Natural antibodies to cytokines can be found in the sera of normal healthy
      individuals in the absence of specific immunostimulation. However, the function,
      impact, and purpose of natural antibody development have yet to be fully
      elucidated. Interleukin (IL)-18 is a cytokine that exerts proinflammatory
      activities and induces natural killer (NK) cell activity. Recombinant human IL-18
      (rHuIL-18) is currently in development as a cancer immunotherapy. In this study,
      the presence of natural antibodies to IL-18 in the sera of normal humans and
      three nonhuman primate species was evaluated by electrochemiluminescence
      immunoassay (ECLIA). Of the human sera tested, 6 of 47 samples were positive for
      natural antibodies to IL-18. Of the nonhuman primate sera tested, 22 of 80
      cynomolgus monkey samples, 4 of 31 rhesus monkey samples, and 2 of 20 chimpanzee
      samples were positive for natural antibodies to IL-18. Natural anti-IL-18
      antibodies were neutralizing in 5 of 22 cynomolgus and 2 of 4 rhesus sera. None
      of the chimpanzee or human sera were able to neutralize IL-18 induction of
      interferon (IFN)-gamma in vitro. In vivo activity of rHuIL-18 was compared in IL
      18 natural antibody-positive and -negative cynomolgus monkeys. The presence of
      natural antibodies to IL-18 did not alter rHuIL-18 systemic exposure levels,
      induction of neopterin, or induction of treatment-induced antibodies following
      intravenous administration of rHuIL-18. In conclusion, our data indicate that, as
      has been found with other cytokines, natural anti-IL-18 antibodies are relatively
      common. Moreover, natural anti-IL-18 antibodies do not appear to influence rHuIL
      18 activity in vivo and are not predictive of a heightened immune response,
      suggesting that natural anti-IL-18 antibodies do not impact IL-18 therapy.
      Finally, our data suggest that the ability to detect natural anti-cytokine
      antibodies may be a useful measure of the adequacy of an assay for deployment in
      clinical trials.

PMID- 14597218
TI  - Effects of housing on the thymic deficiency in dwarf mice and its reversal by
      growth hormone administration.
AB  - Initial studies on T cell development in the Snell Dwarf (dw/dw) strain of mice,
      which are deficient in the production of anterior pituitary hormones, have been
      interpreted to indicate a clear dependence of T cell development on endocrine
      system-derived factors. However, normal thymopoiesis in this strain has also been
      reported. The aim of the present study was to reconcile these contradictory data
      in order to define the role of anterior pituitary hormones in the thymus. The
      results indicated that if female dw/dw mice are housed together with their normal
      sized littermates, thymic cellularity and the frequency of CD4(+)CD8(+)
      thymocytes are markedly reduced. However, administration of growth hormone could
      reverse these decreases seen in the double-positive T progenitor cells. Taken
      together, the data indicate that stress is the unifying parameter that can
      explain the disparate dw/dw mouse literature and suggest that endocrine effects
      on the T cell development can best be understood by interpreting the literature
      in this context.

PMID- 14597219
TI  - Cow's milk stimulated lymphocyte proliferation and TNFalpha secretion in
      hypersensitivity to cow's milk protein.
AB  - Although there is no reliable single laboratory test available for the diagnosis
      of cow's milk allergy, if an allergic mechanism is suspected, a number of
      laboratory studies may be useful in delineating specific proteins responsible for
      these disorders. In the current study we analyzed in vitro lymphocyte
      proliferation assays, specific secretion of TNFalpha in supernatant cultures and
      specific IgE, IgG, and IgA in a group of patients with hypersensitivity to cow's
      milk antigens. The stimulation index against a cow's milk antigen mixture, alpha
      lactalbumin, beta-lactoglobulin, and casein was significant higher in the group
      of patients maintained on cow's milk-free diet for less than 4 months compared
      with the values observed in the control group and in the group of patients
      without a close contact to cow's milk proteins. A significant increase in TNF
      alpha secretion was observed in supernatants from patients with close contact to
      cow's milk (CM). Specific IgE was detected in 59.3% of the patients, with higher
      specific IgE levels in patients who were not positive for the proliferation
      assay, suggesting a clear difference in the two mechanisms proposed as effectors
      in this disease. No differences in specific IgG and IgA levels were observed
      between the patient group and the control group, with a great dispersion among
      individuals in all groups tested. We conclude that a combination of the assays
      tested in this study, such as proliferative assay of peripheral blood mononuclear
      cells to CM, the quantitation of TNFalpha in culture supernatants, and serum
      specific IgE determination, are useful laboratory tests to identify cow's milk
      allergy among patients with immediate and non immediate adverse reactions,
      reducing the need for food allergen challenges in young children.

PMID- 14597220
TI  - Kinetic analysis of the development of pancreatic lesions in mice infected with a
      murine retrovirus.
AB  - Sjogren's syndrome (SjS)-like sialoadenitis and exocrine pancreatitis were
      induced in mice infected with LP-BM5 murine leukemia virus, which induces a
      severe immunodeficiency termed murine AIDS (MAIDS). All mice with MAIDS showed
      advancing cellular infiltration around the pancreatic ducts as well as systemic
      exocrinopathy. The primary target tissue of the pancreas was acinar cells, and
      the pancreatic islets were well preserved until a late phase of the disease.
      Immunofluorescence and flow cytometry demonstrated that CD4(+) T cells, Mac-1(+)
      cells, and B220(+) cells were major inflammatory components, and IFN-gamma and IL
      10 were mainly detected on CD4(+) T and Mac-1(+) cells in the pancreas. Both Th1
      and Th2 cells were found. TUNEL(+) apoptotic cells were mostly detected among
      pancreas-infiltrating cells. Fas ligand and TNF-alpha were also detected among
      pancreas-infiltrating cells, whereas Fas was rarely expressed in the pancreatic
      acinar cells. Thus, MAIDS mice could be valuable for analyzing the pathogenesis
      of autoimmune-related pancreatitis associated with SjS.

PMID- 14597221
TI  - Soluble L-selectin, a marker of immune activation, in neonatal infection.
AB  - L-Selectin is an adhesion molecule shed from the surface of lymphocytes and
      granulocytes upon activation. Soluble L-selectin in the plasma can thus reflect
      immune activation and is elevated in several pathological states. Our objective
      was to evaluate plasma levels of L-selectin as an immune activation marker in
      neonates and to determine whether it can serve as a marker of infection, either
      neonatal or congenital, or if it is affected by the mode of delivery and
      obstetrical or perinatal complications. A solid-phase ELISA was used on 89 sera
      from neonates less than 2 days of age, according to the manufacturer's
      instructions. Levels of soluble L-selectin in the neonate were lower than those
      of older infants and children and comparable to the levels seen in adults. There
      was no difference between levels of soluble L-selectin of premature (median, 1172
      ng/ml) and full-term babies (median, 1151 ng/ml) or between babies born via
      vaginal (median, 1233 ng/ml) or cesarean delivery (median, 1146 ng/ml).
      Conditions such as preeclampsia or administration of steroids to the mother did
      not affect the levels of L-selectin in the neonate. In contrast, the presence of
      maternal clinical chorioamnionitis resulted in an increase in levels of L
      selectin in the neonate (median, 1377 vs 1072 ng/ml, p = 0.02), as did neonatal
      sepsis (median, 1331 vs 1149 ng/ml, p = 0.026). Soluble L-selectin, and thus
      immune activation level, is highest in neonates with neonatal infection and needs
      to be further evaluated as a surrogate marker for diagnosing sepsis in the
      neonate.

PMID- 14597222
TI  - Lack of graft-versus-host-like pathology in mercury-induced autoimmunity of Brown
      Norway rats.
AB  - The repeated administration of mercury to Brown Norway (BN) rats induces the
      production of autoantibodies to laminin 1 and other autoantigens, accompanied by
      renal deposition of immunoglobulins and a membranous glomerulonephropathy. A
      graft-versus-host-like (GVHL) syndrome, characterized by widespread necrotizing
      leukocytoclastic vasculitis of the bowel, skin, and other tissues, has also been
      observed after mercury treatment of BN rats. These findings have suggested that
      the autoimmunity caused by the administration of mercury to BN rats may result as
      a xenobiotic-induced GVHL effect under the control of OX22+ T lymphocytes.
      However, previous studies of mercury-induced autoimmunity have never reported any
      evidence of GVHL lesions. Therefore, we have carefully examined various tissues
      from a large group of BN rats injected with HgCl(2) to identify possible areas of
      inflammatory reactions that may have been unnoticed in previous investigations.
      In addition, we have determined by flow cytometry whether exposure to mercury
      results in percentage and numerical alterations of OX22+ or other lymphocyte
      subpopulations in lymphoid organs of HgCl(2)-treated BN rats. The present article
      confirms that mercury induces autoimmune responses to laminin 1 but does not
      corroborate the hypothesis of a GVHL syndrome regulated by OX22+ lymphocytes.
      First, changes in OX22+ cells during treatment with HgCl(2) were infrequent and
      had no significant correlation with the kinetics of autoimmune responses to
      laminin 1. Second, we detected no GVHL lesions in skin and intestine of mercury
      treated BN rats.

PMID- 14597223
TI  - Chemokine receptor CCR5 is not required for development of experimental
      autoimmune gastritis.
AB  - Experimental autoimmune gastritis (EAG) is a model of human autoimmune gastritis,
      the underlying cause of pernicious anaemia. It is characterised by gastric
      mononuclear cell infiltrates, destruction of parietal and zymogenic cells, and
      autoantibodies to parietal cell-associated H(+)/K(+) ATPase. Here, we have
      investigated the role of CCR5 in the development of EAG. We found that the
      development of EAG was not prevented in CCR5-deficient mice. Using reverse
      transcriptase analysis of stomachs from normal and gastritic mice we found no
      difference in expression of CCR5 and its chemokine ligands MIP-1alpha, MIP-1beta,
      and RANTES. We also found that the CCR5 antagonist met-RANTES failed to prevent
      the development of EAG induced by neonatal thymectomy. These observations suggest
      that the CC chemokine receptor CCR5 is not essential for development of EAG.

PMID- 14597224
TI  - Systemic FIV vector administration: transduction of CNS immune cells and Purkinje
      neurons.
AB  - The systemic effects of gene therapy have been previously described in a variety
      of peripheral organs following intravenous administration or intraperitoneal
      inoculation of viral vectors, as well as in the brain following intracranial
      administration. However, limited information is available on the ability of viral
      vectors to cross the blood-brain barrier and infect cells located within the
      central nervous system (CNS). We employed a VSV-G pseudotyped FIV(lacZ) vector
      capable of transducing dividing, growth-arrested, as well as post-mitotic cells
      with the reporter gene lacZ. Adult mice were injected intraperitoneally with
      FIV(lacZ), and the expression of beta-galactosidase was studied 5 weeks following
      treatment in the brain, liver, spleen and kidney by X-gal histochemistry and
      immunocytochemistry. Interestingly, relatively low doses of FIV(lacZ)
      administered intraperitoneally lead to beta-galactosidase detection in the brain
      and cerebellum. The identity of these cells was confirmed by double
      immunofluorescence, and included CD31-, CD3- and CD11b-positive cells.
      Fluorescent microspheres co-injected with FIV(lacZ) virus were identified within
      mononuclear cells in the brain parenchyma, suggesting infiltration of peripheral
      immune cells in the CNS. Cerebellar Purkinje neurons were also transduced in all
      adult-injected mice. Our observations indicate that relatively low doses of
      FIV(lacZ) administered intraperitoneally resulted in the transduction of immune
      cells in the brain, as well as a specific subset of cerebellar neurons.

PMID- 14597225
TI  - Upregulation of gp130 and differential activation of STAT and p42/44 MAPK in the
      rat hippocampus following kainic acid-induced seizures.
AB  - We investigated the activation and cellular distribution of two signaling
      pathways, the signal transducers and activators of transcription (STATs) and
      mitogen-activated protein kinases (MAPKs) following kainic acid (KA)-induced
      seizures, in relation to the expression of gp130, a common cytokine signal
      transducer for the interleukin (IL)-6 family of cytokines. Rapid and short
      lasting upregulation of gp130 was observed in the granule cells. This became
      evident in astrocytes by 3 h, increased progressively to peak at 3 days, and was
      sustained for 10 days. STATs, including STAT1 and STAT3, and p42/44 MAPK were
      activated in distinct cellular and spatial distributions within the hippocampus
      following seizures. A rapid and sustained seizure-induced activation of STAT3 and
      STAT1, revealed by nuclear STAT3 and STAT1 immunoreactivities, was observed
      exclusively in reactive astrocytes in the hippocampus, nearly coinciding with the
      time course of gp130 expression; however, STAT3 activation was greater. In
      contrast, seizure induced the rapid and transient activation of p42/44 MAPK in a
      subpopulation of hippocampal neurons and in astrocytes, although with weaker
      staining intensity. Two signaling pathways involving gp130, STATs and MAPK, were
      differentially activated in reactive astrocytes after KA injection, indicating
      that STATs and MAPK may differentially mediate the astroglial reaction in the rat
      hippocampus after KA-induced seizures.

PMID- 14597226
TI  - Laminar distribution of NMDA receptor subunit (NR1, NR2A, NR2B) expression during
      the critical period in cat visual cortex.
AB  - Changes in NMDA subunit composition may be part of the molecular basis for
      critical period plasticity. The present study used immunohistochemistry to
      determine developmental changes in the laminar distribution of the three major
      cortical NMDA subunits (NR2A, NR2B, NR1) during the critical period in cat visual
      cortex. For all three subunits, at 1 week staining was concentrated in two bands:
      an upper band consisting of layer I, the compact zone and the upper half of the
      cortical plate; a lower band consisting of layers V and VI. In the lower part of
      the cortical plate (immature layer IV) staining was very low. For NR2A and NR2B,
      immunoreactivity in layer IV remained low until 10 weeks of age. At 20 weeks and
      adult, layer IV filled in and NR2A and NR2B label was rather uniform across all
      layers. NR1 showed a developmental pattern of expression different from NR2A and
      NR2B after 1 week. At 5 and 10 weeks, label was prominent in layer IV and
      superficial layers, but low in layers V and VI. The main change after 10 weeks
      was a progressive decrease in staining, such that in older animals label was
      markedly densest in superficial layers. Thus, during the rise of the critical
      period, NR1 is the dominant subtype in layer IV and could play a role in
      anatomical ocular dominance column formation and plasticity. At the same time,
      NR2A and NR2B subunits are concentrated outside layer IV, and could be related to
      physiological plasticity in extragranular layers, which precedes and outlasts
      plasticity in layer IV. For all three NMDA receptor subunits, the laminar
      distribution was similar in normal and dark reared visual cortex at 20 weeks,
      indicating that the developmental changes in laminar pattern of expression are
      independent of visual input.

PMID- 14597227
TI  - Analysis of cellular, transgenic and human models of Huntington's disease reveals
      tyrosine hydroxylase alterations and substantia nigra neuropathology.
AB  - Huntington's disease (HD) is a progressive, autosomal dominant neurodegenerative
      disorder that is pathologically characterized by a striatal-specific
      degeneration. Aberrant dopamine neurotransmission has been proposed as a
      mechanism underlying the movement disorder of HD. We report that the enzymatic
      activity of tyrosine hydroxylase (TH), the rate-limiting enzyme for dopamine
      biosynthesis, is decreased in a transgenic mouse model of HD. In addition, mutant
      huntingtin was found to disrupt transcription of TH and dopamine beta-hydroxylase
      (DbetaH) promoter reporter constructs. In situ hybridization revealed extensive
      loss of TH mRNA and decreased dopaminergic cell size in human HD substantia
      nigra. TH-immunoreactive protein was reduced in human grade 4 HD substantia nigra
      by 32% compared to age-matched controls. These findings implicate abnormalities
      in dopamine neurotransmission in HD and may provide new insights into targets for
      pharmacotherapy.

PMID- 14597228
TI  - The Ewing's sarcoma protein interacts with the Tudor domain of the survival motor
      neuron protein.
AB  - The survival motor neuron (SMN) gene is the spinal muscular atrophy (SMA)
      determining gene. Here we report that the SMN protein product interacts in vitro
      and in vivo with the arginine/glycine (RG)-rich RNA binding protein and
      transcription factor, Ewing's sarcoma (EWS). Recently, the SMN encoded Tudor
      domain (exon 3) and the YG-motifs (exon 6) have been shown to be involved in
      binding to RG-rich proteins. Here, we demonstrate that the Tudor domain encoded
      by SMN exon 3 is independently sufficient to mediate the interaction with EWS.
      Synthetic mutations within the Tudor domain, as well as a SMA patient-derived
      mutation within exon 3, reduced the levels of the SMN/EWS interaction. Carboxyl
      terminal SMN mutations that prevent formation of SMN oligomers also indirectly
      reduced EWS binding. A role for arginine methylation has been observed in some RG
      containing SMN-interacting proteins. Here we demonstrate that SMN interacts with
      non-methylated EWS and an EWS-derived RG-containing peptide. In contrast to
      previously reported results, symmetrical dimethylation of the EWS-derived RG
      peptide results in a quantitative increase in the dissociation rate between SMN
      and the symmetrical dimethylated EWS RG-peptide. Consistent with the interaction
      data, endogenous and transiently expressed SMN co-localizes with endogenous EWS
      in a number of cultured cell lines, as well as rat primary neuron cultures. Anti
      sense RNA experiments, however, demonstrate that EWS does not mediate the nuclear
      distribution of SMN or other Cajal body components.

PMID- 14597229
TI  - PDNF, a human parasite-derived mimic of neurotrophic factors, prevents caspase
      activation, free radical formation, and death of dopaminergic cells exposed to
      the Parkinsonism-inducing neurotoxin MPP+.
AB  - The neuraminidase/trans-sialidase of Trypanosoma cruzi, the agent of Chagas'
      disease, promotes differentiation and survival of growth factor-deprived neuronal
      and glial cells. To gain further insights into the possible neuroprotection of
      this parasite-derived counterpart of neurotrophic factors (PDNF), we sought to
      determine whether it mimics growth factors in a cellular model of
      neurodegenerative diseases. Ascertaining cell viability by morphology, vital dye
      exclusion, mitochondrial reducing function, and absence of DNA fragmentation, we
      show here that PDNF rescues from death two dopaminergic neuronal cell lines and
      one differentiated immortalized mesencephalic neurons exposed to the neurotoxin 1
      methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) and its toxic metabolite, 1
      methyl-4-phenylpyridinium (MPP+), both widely used in models of Parkinson's
      disease. We further show that PDNF promoted survival at concentrations comparable
      to bona fide growth factors in a MAPK/Erk activation-dependent manner. PDNF also
      strongly suppresses the overproduction of MPTP-induced reactive oxygen species
      (ROS), and the activation of both initiator caspase-9 and effector caspase-3.
      This down-regulation of ROS and caspases explains, at least in part, the PDNF
      induced salvaging of the dopaminergic cells from the Parkinsonism-promoting
      toxin, confirming the novel and striking functional mimicry by the trypanosome
      neuraminidase of host growth factors in a cellular model of neurodegeneration.

PMID- 14597230
TI  - Accumulation of the amyloid precursor-like protein APLP2 and reduction of APLP1
      in retinoic acid-differentiated human neuroblastoma cells upon curcumin-induced
      neurite retraction.
AB  - Amyloid precursor protein (APP) belongs to a conserved gene family, also
      including the amyloid precursor-like proteins, APLP1 and APLP2. The function of
      these three proteins is not yet fully understood. One of the proposed roles of
      APP is to promote neurite outgrowth. The aim of this study was to investigate the
      regulation of the expression levels of APP family members during neurite
      outgrowth. We observed that retinoic acid (RA)-induced neuronal differentiation
      of human SH-SY5Y cells resulted in increased expression of APP, APLP1 and APLP2.
      We also examined the effect of the NFkappaB, AP-1 and c-Jun N-terminal kinase
      inhibitor curcumin (diferuloylmethane) on the RA-induced expression levels of
      these proteins. We found that treatment with curcumin counteracted the RA-induced
      mRNA expression of all APP family members. In addition, we observed that curcumin
      treatment resulted in neurite retraction without any effect on cell viability.
      Surprisingly, curcumin had differential effects on the APLP protein levels in RA
      differentiated cells. RA-induced APLP1 protein expression was blocked by
      curcumin, while the APLP2 protein levels were further increased. APP protein
      levels were not affected by curcumin treatment. We propose that the sustained
      levels of APP and the elevated levels of APLP2, in spite of the reduced mRNA
      expression, are due to altered proteolytic processing of these proteins.
      Furthermore, our results suggest that APLP1 does not undergo the same type of
      regulated processing as APP and APLP2.

PMID- 14597231
TI  - The effects of deafferentation and exogenous NGF on neurotrophins and
      neurotrophin receptor mRNA expression in the adult superior cervical ganglion.
AB  - Levels of nerve growth factor (NGF) and neurotrophin-3 (NT-3) protein and
      neurotrophin receptor mRNA in adult sympathetic neurons were investigated
      following surgical removal of preganglionic input and/or in vivo administration
      of NGF. Expression of trkC and p75, but not trkA, was significantly decreased
      following a 3-week deafferentation of the superior cervical ganglion (SCG).
      Protein levels of NGF and NT-3 in the SCG were unchanged by deafferentation. A 2
      week intracerebroventricular infusion of NGF without deafferentation resulted in
      enhanced mRNA levels of trkA, trkC, and p75 as well as significantly increased
      NGF and NT-3 protein in the SCG. When NGF infusion followed deafferentation, both
      trkA and p75 showed significant increases while trkC levels were similar to
      control values. NGF protein was not increased in the SCG when deafferentation
      preceded exogenous NGF, yet NT-3 was elevated and levels were similar to cases
      receiving NGF infusion only. These results support a role for preganglionic input
      in trkC and p75 expression in adult sympathetic neurons. The increased levels of
      NT-3 protein and trkC gene expression observed following NGF infusion suggest
      that NGF influences NT-3 regulation in adult sympathetic neurons. In addition,
      the present findings provide evidence that, when preganglionic input is removed
      prior to the NGF infusion, NT-3 effectively competes with NGF for trkA binding.
      Taken together, we propose that NT-3 may play a role in the robust sprouting of
      sympathetic cerebrovascular axons previously observed following NGF
      administration, particularly when deafferentation precedes the NGF infusion
      period.

PMID- 14597232
TI  - Stearic acid facilitates hippocampal neurotransmission by enhancing nicotinic ACh
      receptor responses via a PKC pathway.
AB  - Of a variety of saturated free fatty acids examined here, those with less than 20
      hydrocarbon potentiated responses through Torpedo ACh receptors expressed in
      Xenopus oocytes, and the maximal effect was obtained with stearic acid (C18:0) at
      10 microM (168+/-25% of basal levels 10 min after 10-min treatment). Stearic aid
      (10 microM) also potentiated alpha7 nicotinic ACh receptor responses, being
      evident 110 min after 10-min treatment (219+/-18% of basal levels), and the
      potentiation was inhibited by GF109203X, a selective inhibitor of protein kinase
      C (PKC). In the PKC assay using a reversed-phase HPLC, stearic acid (10 microM)
      enhanced PKC-epsilon activity approximately twice as much as the activity in the
      absence of stearic acid. Stearic acid (10 microM) induced a long-lasting
      facilitation of neurotransmission in the dentate gyrus of rat hippocampal slices,
      and the facilitation was inhibited by GF109203X or alpha-bungarotoxin, an
      inhibitor of alpha7 receptors. The results presented here suggest that stearic
      acid facilitates hippocampal neurotransmission by enhancing alpha7 receptor
      responses via a PKC pathway.

PMID- 14597234
TI  - Anti-mu opioid antiserum against the third external loop of the cloned mu-opioid
      receptor acts as a mu receptor neutral antagonist.
AB  - The region from the third external loop to the C terminus of MOR-1 appeared to be
      critical to the selective binding of MOR-1 ligands as DAMGO and morphine to MOR
      1. To study the pharmacological properties of the third extracellular loop an
      antibody was raised in rabbits against the sequence 304-316 which is unique to
      MOR-1 and includes the third external loop; the anti-MOR-1 antibody was affinity
      purified against the immunogen sequence and characterized by [3H]DAMGO and
      Western blotting; [3H]DPDPE binding assay remained unchanged in the presence of
      the antibody. Anti-MOR-1 IgG was characterized as a neutral antagonist in Chinese
      hamster ovary (CHO) cells hyperexpressing constitutively active MOR-1s; in fact,
      anti-MOR-1 IgG completely reversed the inhibition induced by the MOR-1 agonist
      endomorphin1, endomorphin2, DAMGO and morphine on forskolin stimulated cyclic AMP
      (cAMP) accumulation and attenuated both the action of the selective MOR-1 agonist
      DAMGO to increase [35S]GTPgammaS binding and the action of the MOR-1 inverse
      agonist beta-chlornaltrexamine (CNA) to decrease [35S]GTPgammaS binding.
      Radioligand binding assay using membrane suspensions from CHO cells
      hyperexpressing MOR-1 revealed a significant decreased binding affinity and
      capacity of all the tested MOR-1 selective ligands after preincubation with anti
      MOR-1 IgG. Therefore, the third extracellular loop of MOR-1 appeared to be a key
      element for the binding of MOR-1 ligands.

PMID- 14597233
TI  - In vivo heat-shock response in the brain: signalling pathway and transcription
      factor activation.
AB  - We analysed the expression of the hsp70 gene, the phosphorylation status of
      different members of the mitogen-activated protein kinase (MAPK) family, the
      behaviour of the Akt-GSK3 pathway, as well as the DNA-binding activity of several
      transcription factors, potential targets of these kinases, in the brain of rats
      exposed to a fever-like increase in body temperature. Two different brain
      regions, the cerebellum and the hippocampus, were studied. Hyperthermia caused
      HSF activation and the induction of hsp70 mRNA and protein to a greater extent in
      the cerebellum than in the hippocampus. In the cerebellum, ERK1/2 and p38 MAPK
      phosphorylation were increased by hyperthermia and returned to basal levels
      during the recovery from heat stress, whereas JNK3 phosphorylation decreased and
      recovered to above control levels within 60 min of recovery. JNK1 phosphorylation
      was never modified. In the hippocampus, ERK phosphorylation did not increase but
      rather decreased, whereas the behaviour of p38 MAPK and JNK was similar to that
      observed in the cerebellum. Akt phosphorylation increased after hyperthermia and
      was accompanied by an increased phosphorylation of two substrates, GSK3 and
      FKHRL1, in both brain areas, with a major effect in the cerebellum. DNA-binding
      activities of AP-1, NF-kappaB, and MEF2 were activated by heat shock in the
      cerebellum, whereas only MEF2 was activated in the hippocampus. Our data indicate
      that a physiologically relevant increase in body temperature induces brain injury
      and survival response to it as demonstrated by induction of hsp70 gene expression
      and activation of specific signalling pathways. Reprogramming of gene expression,
      by the specific transcription factors activated, probably plays a central role in
      cell adaptation and survival to heat stress. The hippocampus shows less
      responsiveness to hyperthermia than the cerebellum.

PMID- 14597237
TI  - The role of the matrix metalloproteinases in human endometrial and ovarian
      cycles.
AB  - The matrix metalloproteinases (MMPs) are part of an expanded family of proteins
      called the astacin family of zinc metalloproteinases. The MMPs, probably balanced
      by their tissue inhibitors of metalloproteinases (TIMPs), are essential effectors
      of developmental processes participating in cell migration, cell proliferation,
      apoptosis and tissue morphogenesis. The MMPs regulate the function of
      biologically active molecules as well as fulfilling an important role in
      endothelial cell invasion, angiogenesis and in tumor progression. The dynamic
      normal physiology of the human reproductive system involves almost all of the
      above-mentioned aspects of MMPs activity. This review presents and discusses new
      insights into the role of MMPs, and their TIMPs, in human endometrial cycle and
      ovarian function.

PMID- 14597235
TI  - Depolarization-induced signaling to Ras, Rap1 and MAPKs in cortical neurons.
AB  - In neurons, membrane depolarization triggers pleiotropic signaling which includes
      the activation of the small GTPases, Ras and Rap1, and the mitogen-activated
      protein kinases (MAPKs) Erk1/2. We have studied the intracellular signaling
      mechanisms which regulate these events in mouse-cultured cortical neurons. We
      show that depolarization induces activation of both Ras and Rap1, although with
      different kinetics: Ras activation is strong and fast while Rap1 activation is
      slower and weaker. Blockade of calmodulin affects the GTP-loading of Ras and Rap1
      and prevents the MAPK response. Moreover, protein kinase A (PKA) activity is
      required for depolarization-induced Rap1 activation and full Erk stimulation, but
      is not involved in that of Ras. This PKA-dependent Rap1 activation does not
      require Src family kinases, but, in contrast to Ras, is sensitive to genistein,
      indicating the involvement of a tyrosine kinase-dependent mechanism. Our data
      provide new insights into the regulation of Ras and Rap1 activation in neurons.

PMID- 14597238
TI  - Vaginal breech delivery: is it still an option?
AB  - OBJECTIVE: To provide local data on term breech delivery for future guidance.
      STUDY DESIGN: Retrospective, 'intended-mode-of-delivery' analysis of 711
      antenatally uncomplicated singleton breech deliveries at >or=37 weeks: 445 (63%)
      planned for vaginal delivery (VD) (no fetal growth restriction, fetal weight 2000
      4000 g, adequate pelvic size, maternal consent) and 266 for cesarean section
      (CS). OUTCOME MEASURES: Apgar score, cord blood acid-base status, childhood
      deaths and disability. RESULTS: Perinatal mortality was nil in both groups. Low 1
      min Apgar scores and low arterial cord blood pH were significantly more frequent
      in planned VD, but not low Apgar scores at 5 or 10 min or low venous pH.
      Metabolic acidosis, neonatal intensive care, neonatal seizures, birth trauma,
      childhood death (CS=1), and neurodevelopmental handicaps (CS=2, VD=1) were
      equally common. CONCLUSION: Our results do not disqualify selective vaginal
      breech delivery at term and beyond as an option.

PMID- 14597239
TI  - Uterine artery Doppler blood flow in cases of hydatidiform mole and its
      correlation with beta-hCG.
AB  - OBJECTIVES: To study the correlation between Doppler blood flow and beta-human
      chorionic gonadotropin (hCG), to assess the course of the disease and the follow
      up evaluation. SETTING: This study was conducted in Assiut University Hospital,
      Department of Obstetrics and Gynecology. DESIGN: Longitudinal study. SUBJECTS AND
      METHODS: Fifteen cases of vesicular mole were recruited and followed up. The
      patients were evaluated the day before evacuation of the uterus. This included
      clinical assessment, Doppler uterine artery blood flow velocity waveforms using
      the Doppler indices and assessment of the serum level of beta-hCG. These cases
      were followed up every 2 weeks in the first 2 months, and every month thereafter
      until the 6 month. RESULTS: Twelve patients showed continuous decrease in beta
      hCG level from 1192+/-697 to 6+/-11 IU/ml by the end of the second month.
      Systolic-diastolic (S/D) increased from (2.57+/-1.13) to (15.9+/-2.07)
      (P<0.0001), RI increased from 0.55+/-0.15 to 1.0+/-0.26(P<0.0001) and PI
      increased from 1.02+/-0.47 to 6.12+/-2.34 (P<0.0001). One patient showed a
      fluctuating level of beta-hCG around the same level, and two showed a slowed
      decrease. Doppler indices showed similar results. There is a strong correlation
      between beta-hCG and all Doppler indices throughout the course of follow up: beta
      hCG and S/D r<0.01, beta-hCG and RI r<0.01 and beta-hCG and PI r<0.01.
      CONCLUSION: Doppler ultrasound can be used as an adjuvant tool in the follow up
      of cases of vesicular mole and can predict the progress in the course of the
      disease.

PMID- 14597240
TI  - A population-based case-control teratological study of vaginal econazole
      treatment during pregnancy.
AB  - OBJECTIVE: To study human risk and benefit of vaginal econazole treatment during
      pregnancy. MATERIALS AND METHODS: Pair analysis of cases with congenital
      abnormalities and matched controls in the population-based dataset of the
      Hungarian Case-Control Surveillance of Congenital Abnormalities (HCCSCA), 1980
      1996. RESULTS: Of 38151 pregnant women who had newborn infants without any
      congenital abnormalities (control group), 122 (0.3%), of 22843 case pregnant
      women who had newborns or fetuses with congenital abnormalities, 68 (0.3%) used
      vaginal suppository of econazole (crude prevalence odds ratio (POR): 0.9, with
      95% confidence interval (CI): 0.7-1.3). The matched case-control pair analysis
      did not indicate any teratogenic potential of econazole use during the second and
      third months of gestation, i.e. in the critical period for most major congenital
      abnormalities. CONCLUSION: Treatment with econazole during pregnancy does not
      indicate any teratogenic risk to the fetus.

PMID- 14597241
TI  - Cerebrospinal fluid nitric oxide level changes in preeclampsia.
AB  - OBJECTIVE: The purpose of this study was to determine the level of nitric oxide
      (NO) metabolites, nitrite and nitrate in human cerebrospinal fluid (CSF) and
      serum and to assess whether there is any relationship among CSF, serum nitrate
      nitrite levels and preeclampsia. STUDY DESIGN: Twenty-one preeclamptic and 27
      healthy pregnant women as control group who underwent cesarean section (C/S) were
      included in the study. Before administering local anesthetic for spinal
      anesthesia, 2 ml CSF and 4 ml venous blood sample were taken. CSF and serum total
      nitrite, direct nitrite and nitrate levels were determined
      spectrophotometrically. RESULTS: CSF total nitrite, direct nitrite and nitrate
      levels were significantly different between the two groups (21.00+/-1.68, 8.28+/
      0.89 and 12.71+/-1.08 micromol/l, respectively versus 15.53+/-1.49, 5.57+/-0.39
      and 9.96+/-1.45 micromol/l, respectively, P<0.05). Significantly higher serum
      nitrate level was found (31.84+/-2.31 micromol/l) in the control group compared
      to the preeclamptic group serum nitrate level (25.06+/-2.02 micromol/l).
      Statistical comparisons were performed by the Mann-Whitney U-test. CONCLUSION:
      CSF-NO is significantly higher but serum NO is lower in preeclamptic group
      compared with control group may suggest independent regulation of NO in the two
      compartments. The determination of CSF-NO metabolites could be useful to clarify
      whether increased NO production is predominantly associated with poor perfusion
      of the brain in preeclampsia.

PMID- 14597242
TI  - Thrombotic thrombocytopenic purpura: medical and biological monitoring of six
      pregnancies.
AB  - BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is a rare cause of severe
      thrombocytopenia in pregnancy. METHODS: Six pregnancies in five patients with TTP
      were followed prospectively over 5 years. Ultralarge von Willebrand factor
      (ULvWF) multimers and cleaving protease (cp) levels were measured. RESULTS: TTP
      relapsed, complicating four of the six pregnancies. Of three patients who
      relapsed, two had complete or partial vWF-cleaving protease (vWF-cp) deficiency,
      and one had a normal vWF-cleaving protease level. In all three we found abnormal
      UL multimers. The two women who did not relapse had normal vWF-cleaving protease
      level and an absence or loss of UL multimers. CONCLUSIONS: Pregnant patients with
      a history of TTP must be followed in a tertiary obstetric unit with
      plasmapheresis available. Influence of vWF-cleaving protease and vWF multimeric
      abnormalities on TTP relapsing during pregnancy has to be evaluated in a further
      multicentre study.

PMID- 14597243
TI  - Expression of angiopoietic factors in normal and type-I diabetes human placenta:
      a pilot study.
AB  - OBJECTIVES: Morphological changes of blood vessel wall have been described in
      placenta from pregnancies complicated by diabetes mellitus type-I. STUDY DESIGN:
      We measured mRNA expression of vascular endothelial growth factor (VEGF),
      angiopoietin 1 and 2 (Ang-1 and Ang-2), their receptors VEGFR-1, VEGFR-2, Tie-2,
      fibroblast growth factor 2 (FGF-2), and its receptor FGF-2R in placental tissue
      of diabetes type-I patients, in normal term placenta, and endometrium of non
      pregnant women by real time reverse transcriptase PCR. RESULTS: The expression of
      Ang-2 and VEGFR-1 mRNAs was significantly higher in placenta (P<or=0.01). The
      expression of VEGF and VEGFR-2 mRNAs was significantly lower in normal term or
      diabetes type-I placenta compared to human endometrium (P<or=0.01). We did not
      detect a significant difference in the expression of Ang-1, Ang-2, Tie-2, VEGF,
      VEGFR-1, VEGFR-2, FGF-2, and FGF-2R in normal and diabetes type-I placenta.
      CONCLUSION: These data show differential expression of Ang-2, VEGFR-1, VEGF, and
      VEGFR-2 in placenta and endometrium. The expression of Ang-1, Ang-2, Tie-2, VEGF,
      VEGFR-1, VEGFR-2, FGF-2, and FGF-2R was not different in normal and type-I
      diabetes placenta.

PMID- 14597244
TI  - Factor V Leiden, prothrombin 20210G --> A, methylenetetrahydrofolate reductase
      677C --> T and plasminogen activator inhibitor 4G/5G polymorphism in women with
      pregnancy-related venous thromboembolism.
AB  - OBJECTIVE: To establish the prevalence of inherited and acquired risk factors for
      development of venous thromboembolism (VTE) in pregnancy and the puerperium.
      STUDY DESIGN: In a retrospective study, 30 women with a history of objectively
      confirmed venous thromboembolism during pregnancy or the puerperium were studied.
      Fifty-six women with normal pregnancies were included as controls. Antithrombin,
      protein C, protein S, lupus anticoagulants, homocysteine, factor V Leiden
      mutation, prothrombin 20210G-->A polymorphism, methylenetetrahydrofolate
      reductase (MTHFR) 677C-->T polymorphism and the -675 (4G/5G) polymorphism in
      plasminogen activator inhibitor 1 gene were analysed. RESULTS: At least one
      thrombophilic defect was observed in 16 (53.3%) cases and in 12 (21.4%) controls
      (P=0.003); factor V Leiden in 8 (26.7%) cases and 3 (5.7%) controls (P=0.009);
      prothrombin 20210G-->A polymorphism in 8 (26.7%) cases and 4 (7.5%) controls
      (P=0.021) and antithrombin deficiency in 4 (13.3%) cases and in 1 (1.8%) control
      (P=0.029). Other inherited and acquired risk factors were similarly distributed
      among cases and controls. CONCLUSION: Women with pregnancy-related venous
      thromboembolism have an increased prevalence of inheritable thrombophilic defects
      predisposing them to an increased risk of thrombosis.

PMID- 14597245
TI  - Flemish obstetricians' personal preference regarding mode of delivery and
      attitude towards caesarean section on demand.
AB  - OBJECTIVES: To assess Flemish obstetricians' preferences about mode of delivery
      for themselves or their partners and to determine the frequency of caesarean
      section on demand in Flanders. STUDY DESIGN: A structured anonymous postal
      questionnaire was sent to all 672 registered gynaecologist-obstetricians in
      Flanders. RESULTS: The response rate was 44%. In the case of an uncomplicated
      singleton first pregnancy with a cephalic presentation 2% preferred elective
      caesarean section. There was no difference between male and female obstetricians.
      Seventy percent said that they would never perform caesarean section on demand.
      At least 2.6% of all caesarean sections in Flanders seems to be performed on
      patient's demand. CONCLUSION: The attitude of Flemish gynaecologist-obstetricians
      is clearly in favour of vaginal delivery both for themselves, their partners and
      their patients.

PMID- 14597246
TI  - Preconception nutritional intake and lifestyle factors: first results of an
      explorative study.
AB  - OBJECTIVE: To describe nutritional intake and lifestyle factors in women planning
      pregnancy. STUDY DESIGN: A semi-quantitative, 1-month food frequency
      questionnaire and a questionnaire on health practices and personal views were
      filled out at home and verified by telephone interview. RESULTS: One hundred and
      one women agreed to participate and data of 69 women were eligible for
      evaluation. Women planning pregnancy (n=46) consumed significantly more saturated
      fats and proteins, less carbohydrates and higher median intakes of Vitamin A,
      thiamin, riboflavin, calcium, selenium, magnesium and iron than controls (n=23;
      P<0.05). However, the percentage of women planning pregnancy with intakes below
      recommended dietary allowances was 74% for iron, 59% for selenium, 48% for
      Vitamin A and 91% for copper. Ninety-six percent and 20% of them reported alcohol
      use and smoking, respectively. CONCLUSIONS: Nutritional intake of women in the
      preconception period appears to be inadequate. Efforts to increase awareness of a
      healthy diet and lifestyle before and throughout pregnancy should be continued.

PMID- 14597247
TI  - Analysis of 508 infertile male patients in south-western Finland in 1980-2000:
      hormonal status and factors predisposing to immunological infertility.
AB  - OBJECTIVE: To analyse the factors predisposing to male immunological infertility
      from the hospital records of 508 patients that had been treated for infertility
      in the Turku University Central Hospital from 1980 to 2000. In addition, the
      hormonal status was investigated at the beginning of treatment. RESULTS: Patients
      with a history of mumps, or either a fresh varicocele or a history of varicocele
      had statistically significant lower levels of MAR antisperm antibodies (ASAs)
      than patients with no such conditions. Repair of varicocele (either surgical or
      embolisation), showed a statistically significant enhancement of the total sperm
      cell counts in ejaculates, but it appeared not to have any influence on other
      parameters of the semen analysis (mobility and morphology). Of all male
      infertility patients, 66.3% had normal hormonal status at the beginning of
      treatment, 12.6% of patients had hypotestosteronemia and 22.1% had subclinical
      hypogonadism. Patients with subclinical hypogonadism had lower total sperm cell
      count in ejaculates than patients with normal hormonal status although they had
      statistically significant more offspring. In addition, it appeared that mumps
      orchitis as well as smoking and alcohol abuse are risk factors for subclinical
      hypogonadism. CONCLUSION: No clear predisposing factor for male immunological
      infertility could be found. However, patients with subclinical hypogonadism
      differed from other male infertility patients and thus may form a special group
      among the male infertility patients.

PMID- 14597248
TI  - Respective consequences of abdominal, vaginal, and laparoscopic hysterectomies on
      women's sexuality.
AB  - OBJECTIVE: To determine the relative effects of abdominal, vaginal or
      laparoscopic approaches for hysterectomy on female sexuality. STUDY DESIGN: One
      hundred and seventy women who underwent abdominal (n=68), vaginal (n=67), and
      laparoscopic (n=35) hysterectomy for benign disease were studied. Pre- and
      postoperative sexuality was assessed by questionnaire. RESULTS: Overall,
      sexuality after hysterectomy remained unchanged in 60.4% of cases, and improved
      or deteriorated in 21.3 and 18.3%, respectively. Postoperative delay in resuming
      sexual activity was shorter after vaginal (45.2+/-6.7 days) hysterectomy than
      after abdominal hysterectomy (62.4+/-9.3 days). Deterioration of sexual function
      occurred more frequently after abdominal hysterectomy (24%) than after vaginal
      (13.5%) or laparoscopic (8.5%) hysterectomy. CONCLUSION: These results indicate
      that the impact of vaginal and laparoscopic hysterectomy on women's sexuality may
      be milder than that of abdominal hysterectomy.

PMID- 14597249
TI  - Planning of empirical antibiotic therapy for women with pelvic inflammatory
      diseases: a geographical area-specific study.
AB  - OBJECTIVE: Elaboration of an empiric antibiotic regimen for women with pelvic
      inflammatory disease (PID) for a geographical area in eastern Hungary. STUDY
      DESIGN: Pathogens were identified by culturing or polymerase chain reaction (PCR)
      from 2215 patients with suspected PID between 1 January 1999 and 31 December
      2001. Empiric guidelines for PID treatment were based on susceptibility testing
      of the recovered bacteria, patient acceptance and cost-effectiveness of drugs and
      recommendations of earlier studies. RESULTS: Chlamydia trachomatis was detected
      in 11%, Neisseria gonorrhoeae in 2%, Streptococcus spp. in 17%, Enterococcus spp.
      9%, genital mycoplasmas in 25%, all obligate anaerobic pathogens in 30% of the
      patients. All antibiotics chosen for our regimen were effective in vitro against
      one or more recovered pathogens at least in 80%; this regimen produced 98%
      clinical cure rate in mild cases of PID. CONCLUSION: Early detection and prompt
      empirical antimicrobial therapy adapted to the local microflora and its
      resistance pattern can lead to good clinical results.

PMID- 14597250
TI  - Influence of surgery and postoperative therapy and tumor characteristics on
      patient prognosis in advanced ovarian carcinomas.
AB  - OBJECTIVES: The prognosis in advanced ovarian cancer depends on clinical,
      morphological, biological and therapeutic variables. However, little is known
      about their real influences and interrelationships. STUDY DESIGN: One hundred and
      nineteen long-term, follow-up patients with advanced ovarian carcinoma were
      analyzed. Overall survival was related to the extent of debulking surgery,
      response to chemotherapy and several clinicomorphological, histopathological, and
      immunohistochemical variables. RESULTS: Among all variables, both radical surgery
      and response to chemotherapy exerted the greatest influence on patient prognosis
      as shown in both univariate and multifactorial analyses. Most established
      prognostic factors were of minor importance. Success of chemotherapy correlated
      with lower residual tumor volume, CA125 expression, FIGO-stage, and serous tumor
      type. CONCLUSION: Prognosis and chemotherapeutic success in advanced ovarian
      cancer seem to be interrelated and may be influenced by the intensity of surgical
      interventions. This demands for greatest cytoreduction during initial surgery and
      correction for residual tumor volume and success of therapy in studies of
      prognostic factors.

PMID- 14597251
TI  - Uterine cavity matrix metalloproteinases and cytokines in patients with
      leiomyoma, adenomyosis or endometrial polyp.
AB  - OBJECTIVE: To determine whether leiomyoma, adenomyosis and endometrial polyps are
      associated with changes in uterine cavity matrix metalloproteinases (MMP-2 and
      MMP-9) and cytokines. STUDY DESIGN: Uterine cavity irrigation was performed in
      women with leiomyoma, adenomyosis and endometrial polyps, and in women with a
      normal uterus. MMP-2 and MMP-9 were assayed in the uterine washings by gelatin
      zymography. For individual subjects, the total MMP level was obtained by adding
      the semi-quantitative scores of band densities related to gelatinases in the
      zymograms. Interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha),
      interferon-gamma (IFN-gamma) and transforming growth factor-beta1 (TGF-beta1)
      were measured using enzyme-linked immunosorbant assay (ELISA) kits. RESULTS: The
      uterine cavity of patients with leiomyoma, adenomyosis and endometrial polyps had
      significantly higher MMP scores than controls. Although the mean IL-1beta levels
      were elevated in uteri harboring a pathology compared with the normal uteri, the
      cytokine was significantly elevated only in the adenomyotic group. Significantly
      elevated levels of IFN-gamma were found in uteri with leiomyoma and endometrial
      polyps. Uterine washings from leiomyoma and adenomyosis contained significantly
      elevated mean levels of TGF-beta1 compared with controls, while TNF-alpha was
      significantly higher only in leiomyoma. When uterine cytokine levels were
      compared in relation to individual MMP levels a significant relationship was
      found between TGF-beta1 and elevated levels of MMP-9 and total MMPs in leiomyoma.
      A significant relationship was also found between IL-1beta and elevated levels of
      MMP-2, MMP-9 and total MMPs in the endometrial polyp group. CONCLUSION: The
      uterine cavity in leiomyoma, adenomyosis and endometrial polyps contains elevated
      levels of MMPs and cytokines compared with the normal uterus. In some pathologies
      elevated cytokines are associated with elevated MMPs.

PMID- 14597252
TI  - Small bowel volvulus in pregnancy.

PMID- 14597253
TI  - Spontaneous rupture of the uterus caused by placenta percreta at 28 weeks of twin
      pregnancy.
AB  - A woman at 28 weeks' gestation in a twin pregnancy developed spontaneous rupture
      of the uterus caused by placenta percreta. Due to severe intraabdominal
      haemorrhage a laparotomy was performed and the bodies and parts of the dead
      foetuses were removed with sutured closer of the ruptured uterus. The
      predisposing factors, the diagnostic approaches and the possible surgical
      managements of the disease are summarised.

PMID- 14597254
TI  - Spontaneous normalization of ovarian function and pregnancy in a patient with
      resistant ovary syndrome.
AB  - We report a case of normalization of ovarian function followed by pregnancy in a
      young woman with hypergonadotropic ovarian failure. The change from the
      hypergonadotropic to the normogonadotropic state was followed by serial hormone
      determination and ultrasonography. It occurred within a few days and was
      accompanied by an increase in estradiol as well as circulating Inhibin A
      concentrations.

PMID- 14597255
TI  - Multiple myeloma diagnosed during early pregnancy: a case report.
AB  - Only five pregnant women with multiple myeloma have been reported in literature.
      We present the case of one woman with multiple myeloma diagnosed in early
      pregnancy, who decided to postpone therapy until after delivery. A cesarean
      section was performed at the 34th week due to the progression of the disease and
      a normal healthy baby was delivered.

PMID- 14597256
TI  - Recurrent leiomyomatosis peritonealis disseminata after hysterectomy and
      bilateral salpingo-oophorectomy during combined hormone replacement therapy.
AB  - Leiomyomatosis peritonealis disseminata is a rare disease characterised by the
      occurrence of multiple smooth muscle cells building up tumour nodules within the
      peritoneal cavity. Approximately 50 cases of this disease have been reported in
      the world literature. To our knowledge, this is the first case reporting the
      recurrence of leiomyomatosis peritonealis disseminata during combined hormone
      replacement therapy after hysterectomy and bilateral salpingo-oophorectomy and
      six laparotomies because of recurrence of the disease.

PMID- 14597257
TI  - Specialist life--Renate Huch.

PMID- 14597259
TI  - The cell outgrowth secretory endosome (COSE): a specialized compartment involved
      in neuronal morphogenesis.
AB  - The role of intracellular membrane trafficking in cellular morphogenesis is still
      unclear. We propose here a prominent function of a recently identified
      compartment that we propose to call the cell outgrowth secretory endosome (COSE),
      the exocytosis of which is controlled by the v-SNARE TIVAMP and by cell-cell
      adhesion.

PMID- 14597260
TI  - The dependence receptors DCC and UNC5H as a link between neuronal guidance and
      survival.
AB  - Netrins are secreted proteins that play a crucial role in neuronal migration and
      in axon guidance during the development of the nervous system. Netrin-1 has been
      shown to interact with the transmembrane receptors DCC and UNC5H and these
      receptors appeared of key importance in mediating the chemotropic activity of
      netrin-1. Before the discovery of DCC as a netrin-1 receptor, the gene encoding
      DCC was proposed as a putative tumor suppressor gene because one DCC allele was
      deleted in roughly 70% of colorectal cancers and its expression was often reduced
      or absent in colorectal cancer tissues. A putative explanation for such dual
      roles has recently emerged with the observation that DCC belongs to the growing
      family of dependence receptors. Such receptors share the property of inducing
      apoptosis in the absence of ligand, hence creating a cellular state of dependence
      on the ligand. The other netrin-1 receptors UNC5H were also subsequently proposed
      to be dependence receptors, suggesting that netrin-1 may not only be a
      chemotropic factor for neurons but also a survival factor. We describe here
      netrin-1 and its receptors, together with the molecular signaling pathways
      initiated upon netrin-1 binding or upon netrin-1 withdrawal leading respectively
      to axonal/neuronal guidance or cell death induction. We then conclude to the
      possible roles of DCC and UNC5H pro-apoptotic activities in both nervous system
      development and tumorigenesis.

PMID- 14597261
TI  - Dynamic compartmentalization of the voltage-gated sodium channels in axons.
AB  - One of the major physiological roles of the neuronal voltage-gated sodium channel
      is to generate action potentials at the axon hillock/initial segment and to
      ensure propagation along myelinated or unmyelinated fibers to nerve terminal.
      These processes require a precise distribution of sodium channels accumulated at
      high density in discrete subdomains of the nerve membrane. In neurons,
      information relevant to ion channel trafficking and compartmentalization into sub
      domains of the plasma membrane is far from being elucidated. Besides, whereas
      information on dendritic targeting is beginning to emerge, less is known about
      the mechanisms leading to the polarized distribution of proteins in axon. To
      obtain a better understanding of how neurons selectively target sodium channels
      to discrete subdomains of the nerve, we addressed the question as to whether any
      of the large intracellular regions of Nav1.2 contain axonal sorting and/or
      clustering signals. We first obtained evidence showing that addition of the
      cytoplasmic carboxy-terminal region of Nav1.2 restricted the distribution of a
      dendritic-axonal reporter protein to axons of hippocampal neurons. The analysis
      of mutants revealed that a di-leucine-based motif mediates chimera
      compartmentalization in axons and its elimination in soma and dendrites by
      endocytosis. The analysis of the others generated chimeras showed that the
      determinant conferring sodium channel clustering at the axonal initial segment is
      contained within the cytoplasmic loop connecting domains II-III of Nav1.2.
      Expression of a soluble Nav1.2 II-III linker protein led to the disorganization
      of endogenous sodium channels. The motif was sufficient to redirect a
      somatodendritic potassium channel to the axonal initial segment, a process
      involving association with ankyrin G. Thus, it is conceivable that concerted
      action of the two determinants is required for sodium channel
      compartmentalization in axons.

PMID- 14597262
TI  - Transmembrane scaffolding proteins in the formation and stability of nodes of
      Ranvier.
AB  - The function of myelinated fibers depends on the clustering of sodium channels at
      nodes of Ranvier, the integrity of the myelin sheath, and the existence of tight
      axoglial junctions at paranodes, on either sides of the nodes. While the
      ultrastructure of these regions has been known for several decades, recent
      progress has been accomplished in the identification of proteins essential for
      their organization, which depends on the interplay between axons and myelinating
      glial cells. Evolutionary conserved intercellular multimolecular complexes
      comprising proteins of the Neurexin IV/Caspr/paranodin (NCP) family and of the
      immunoglobulin-like cell adhesion molecules superfamily, are essential components
      for the axoglial contacts at the level of paranodes and juxtaparanodes. These
      complexes are able to interact with cytoplasmic proteins of the band 4.1 family,
      providing possible links to the axonal cytoskeleton. While the identification of
      these proteins represents a significant progress for understanding axoglial
      contacts, they also raise exciting questions concerning the molecular
      organization of these contacts and the mechanisms of their local enrichment.

PMID- 14597263
TI  - Neurotransmitter release: the dark side of the vacuolar-H+ATPase.
AB  - Vacuolar-H+ATPase (V-ATPase) is a complex enzyme with numerous subunits organized
      in two domains. The membrane domain V0 contains a proteolipid hexameric ring that
      translocates protons when ATP is hydrolysed by the catalytic cytoplasmic sector
      (V1). In nerve terminals, V-ATPase generates an electrochemical proton gradient
      that is acid and positive inside synaptic vesicles. It is used by specific
      neurotransmitter-proton antiporters to accumulate neurotransmitters inside their
      storage organelles. During synaptic activity, neurotransmitters are released from
      synaptic vesicles docked at specialized portions of the presynaptic plasma
      membrane, the active zones. A fusion pore opens that allows the neurotransmitter
      to be released from the synaptic vesicle lumen into the synaptic cleft. We
      briefly review experimental data suggesting that the membrane domain of V-ATPase
      could be such a fusion pore. We also discuss the functional implications for
      quantal neurotransmitter release of the sequential use of the same V-ATPase
      membrane domain in two different events, neurotransmitter accumulation in
      synaptic vesicles first, and then release from these organelles during synaptic
      activity.

PMID- 14597264
TI  - Calmodulin-dependent regulation of a lipid binding domain in the v-SNARE
      synaptobrevin and its role in vesicular fusion.
AB  - Trans SNARE complex assembly is an essential step in Ca2+-dependent membrane
      fusion, although the SNARE proteins do not bind Ca2+ ions. Studies to evaluate
      how the Ca2+sensor protein calmodulin might regulate this process led to the
      identification of a consensus calmodulin binding motif in the v-SNARE VAMP2. This
      sequence (residues 77-90) is situated precisely C-terminal to the tetanus toxin
      (TeNT) and botulinum B toxin cleavage site (76Q-F77) close to the transmembrane
      anchor. The same domain also binds acidic phospholipids and Ca2+/calmodulin or
      lipid binding are mutually exclusive. Directed mutagenesis of basic or
      hydrophobic residues within this motif reduced interactions with both
      Ca2+/calmodulin and phospholipids to a similar extent. The effects of these
      mutations on Ca2+-dependent exocytosis was explored using an hGH release assay in
      permeabilized pheochromocytoma PC12 cells. Treatment of cells with tetanus toxin
      (TeNT), which cleaves endogenous VAMP, abolished secretion. Secretion could be re
      established by transfecting TeNT-resistant VAMP with mutations (Q76V,F77W) in the
      cleavage site. However rescue of exocytosis was abolished when additional
      mutations (K83A,K87V or W89A,W90A) were introduced that inhibited calmodulin and
      phospholipid binding to VAMP. Thus calmodulin and/or phospholipid binding to the
      membrane proximal region of VAMP is required for Ca2+-dependent exocytosis. We
      speculate that interactions between cis phospholipids at the vesicle surface and
      the membrane proximal region of VAMP inhibits SNARE complex assembly.
      Displacement of these interactions by Ca2+/calmodulin may promote SNARE complex
      assembly and lead to trans interactions between the membrane proximal region of
      VAMP and phospholipids in the plasma membrane.

PMID- 14597265
TI  - Synaptic structure and diffusion dynamics of synaptic receptors.
AB  - Neurotransmitter receptors are concentrated at synaptic sites through
      interactions with specific scaffolding proteins and cytoskeletal elements, but
      can also be found in intracellular compartments or dispersed in the membrane. The
      notion has emerged in recent years that this distribution results from a dynamic
      equilibrium between the different pools of receptors. This equilibrium is
      regulated by neuronal activity and interactions with scaffolding proteins. A
      change in its set point can result in rapid variations in the number of
      functional receptors at synapses such as seen during plasticity. Trafficking of
      receptors in and out of synapses has up to now mainly been viewed within the
      framework of endo/exocytotic processes. After a brief presentation of the
      structure of excitatory and inhibitory synapses, we review data indicating that
      the lateral diffusion of receptors in the plane of the membrane is also a key
      step to regulate receptor stabilization and accumulation at synapses.

PMID- 14597266
TI  - "In vivo" intraneuronal trafficking of G protein coupled receptors in the
      striatum: regulation by dopaminergic and cholinergic environment.
AB  - We have studied "in vivo" neurochemically identified striatal neurons to analyze
      the localisation and the trafficking of dopamine and acetylcholine G protein
      coupled receptors (GPCR) (D1R, D2R, m2R and m4R) under the influence of
      neurotransmitter environment. We have identified receptors in tissue sections
      through immunohistochemical detection at the light and electron microscopic
      level. We have identified receptors in normal animals and after acute and chronic
      stimulations. We have quantified receptors through image analysis at the electron
      microscopic level in relation to various subcellular compartments. Our results
      demonstrate that, in normal conditions, GPCRs are mostly associated with plasma
      membrane of the striatal neurons, mostly at extra-synaptic sites. In certain
      instances (m4R; D2R), receptors have prominent localisation inside the rough
      endoplasmic reticulum. Our results also show that two distinct receptors for a
      same neurotransmitter may have distinct subcellular localisation in a same
      neuronal population (m2R versus m4R) and that the same neurotransmitter receptor
      (m4R) can have distinct localisation in distinct neuronal populations (cytoplasm
      versus cell surface). After acute stimulation, cell surface receptors undergo
      dramatic subcellular changes that involve plasma membrane depletion,
      internalisation in endosomes and in multivesicular bodies. Such changes are
      reversible after the end of the stimulation and are blocked by antagonist action.
      Chronic stimulation also provokes changes in subcellular localisation with
      specific pattern: plasma membrane depletion, and exaggerated storage of receptors
      in rough endoplasmic reticulum and eventually Golgi complex (D1R; m2R and m4R).
      Decreasing chronic receptor stimulation reverses such changes. These results
      demonstrate that, "in vivo", in the striatum, GPCRs undergo complex intraneuronal
      trafficking under the influence of neurochemical environment in conditions that
      dramatically modulate the number of cell surface receptors available for
      interaction with neurotransmitters or drugs. This confirms that "in vivo", the
      trafficking and the subcellular compartmentalization of GPCRs may contribute to
      regulate neuronal sensitivity and neuronal interactions in physiological,
      experimental and pathological conditions, including in therapeutic conditions.

PMID- 14597267
TI  - Evolution and cell biology of dopamine receptors in vertebrates.
AB  - Dopamine, one of main modulatory neurotransmitters of the nervous system acts on
      target cells through two classes of G protein-coupled receptors, D1 and D2. The
      two dopamine receptor classes display different structures, interact with
      different regulatory partners (including heterotrimeric G proteins) and,
      accordingly, have independent evolutionary origins. In vertebrates, each of these
      receptor classes comprises several subtypes, generated by two steps of gene
      duplications, early in vertebrate evolution. In the D1 receptor class, the D1A,
      D1B, D1C and D1D subtypes, and in the D2 class, the D2, D3 and D4 receptor
      subtypes have been conserved in most vertebrate groups. This conservation has
      been driven by the acquisition, by each receptor subtype, of a small number of
      specific properties, which were selected for adaptive purpose in vertebrates.
      Among these properties, affinity for dopamine, the natural ligand, intrinsic
      receptor activity, and agonist-induced desensitization clearly distinguish the
      receptor subtypes. In addition, each dopamine receptor subtype is addressed to a
      specific location within neuronal networks, although detailed information is
      lacking for several receptor subtypes. Receptors localization at diverse
      subcellular places in neurons may also differ from one subtype to another,
      resulting in different ways of regulating cell signalisation. One challenge for
      future research on dopamine and its receptors would be to identify the nature of
      the protein partners and the molecular mechanisms involved in localizing
      receptors to the neuronal plasma membrane. In this respect, the evolutionary
      approach we have undertaken suggests that, due to gene duplications, a reasonable
      degree of freedom exists in the tight organisation of dopamine receptors in
      neurons. This "evolvability" of dopamine systems has been instrumental to adapt
      the vertebrate species to nearly all the possible environments.

PMID- 14597268
TI  - Processing relative clauses in Chinese.
AB  - This paper reports results from a self-paced reading study in Chinese that
      demonstrates that object-extracted relative clause structures are less complex
      than corresponding subject-extracted structures. These results contrast with
      results from processing other Subject-Verb-Object languages like English, in
      which object-extracted structures are more complex than subject-extracted
      structures. A key word-order difference between Chinese and other Subject-Verb
      Object languages is that Chinese relative clauses precede their head nouns.
      Because of this word order difference, the results follow from a resource-based
      theory of sentence complexity, according to which there is a storage cost
      associated with predicting syntactic heads in order to form a grammatical
      sentence. The results are also consistent with a theory according to which people
      have less difficulty processing embedded clauses whose word order matches the
      word order in main clauses. Some corpus analyses of Chinese texts provide results
      that constrain the classes of possible frequency-based theories. Critically,
      these results demonstrate that there is nothing intrinsically easy about
      extracting from subject position: depending on the word order in the main clause
      and in a relative clause, extraction from object position can be easier to
      process in some circumstances.

PMID- 14597269
TI  - Can thematic roles leave traces of their places?
AB  - An important question in the study of language production is the nature of the
      semantic information that speakers use to create syntactic structures. A common
      answer to this question assumes that thematic roles help to mediate the mapping
      from messages to syntax. However, research using structural priming has suggested
      that the construction of syntactic frames may be insensitive to variations in
      thematic roles within messages (Cognition 35 (1990) 1; Psychological Review 99
      (1992) 150). Because these studies involved structural alternations whose syntax
      covaries with the order of thematic roles, it is difficult to assess any
      independent contribution that role information may make to the positioning of
      phrases. In this study, we primed the order of the roles without changing the
      syntactic structure of the sentences produced, and found that the order of the
      roles was influenced by the priming manipulation. This implies that thematic
      roles or the features that differentiate them are active within the mapping
      between messages and sentence structures.

PMID- 14597270
TI  - The role of prosodic boundaries in the resolution of lexical embedding in speech
      comprehension.
AB  - Participants' eye movements were monitored as they heard sentences and saw four
      pictured objects on a computer screen. Participants were instructed to click on
      the object mentioned in the sentence. There were more transitory fixations to
      pictures representing monosyllabic words (e.g. ham) when the first syllable of
      the target word (e.g. hamster) had been replaced by a recording of the
      monosyllabic word than when it came from a different recording of the target
      word. This demonstrates that a phonemically identical sequence can contain cues
      that modulate its lexical interpretation. This effect was governed by the
      duration of the sequence, rather than by its origin (i.e. which type of word it
      came from). The longer the sequence, the more monosyllabic-word interpretations
      it generated. We argue that cues to lexical-embedding disambiguation, such as
      segmental lengthening, result from the realization of a prosodic boundary that
      often but not always follows monosyllabic words, and that lexical candidates
      whose word boundaries are aligned with prosodic boundaries are favored in the
      word-recognition process.

PMID- 14597271
TI  - Frequent frames as a cue for grammatical categories in child directed speech.
AB  - This paper introduces the notion of frequent frames, distributional patterns
      based on co-occurrence patterns of words in sentences, then investigates the
      usefulness of this information in grammatical categorization. A frame is defined
      as two jointly occurring words with one word intervening. Qualitative and
      quantitative results from distributional analyses of six different corpora of
      child directed speech are presented in two experiments. In the analyses, words
      that were surrounded by the same frequent frame were categorized together. The
      results show that frequent frames yield very accurate categories. Furthermore,
      evidence from behavioral studies suggests that infants and adults are sensitive
      to frame-like units, and that adults use them to categorize words. This evidence,
      along with the success of frames in categorizing words, provides support for
      frames as a basis for the acquisition of grammatical categories.

PMID- 14597272
TI  - Not so fast! (and not so frugal!): rethinking the recognition heuristic.
AB  - The 'fast and frugal' approach to reasoning (Gigerenzer, G., & Todd, P. M.
      (1999). Simple heuristics that make us smart. New York: Oxford University Press)
      claims that individuals use non-compensatory strategies in judgment--the idea
      that only one cue is taken into account in reasoning. The simplest and most
      important of these heuristics postulates that judgment sometimes relies solely on
      recognition. However, the studies that have investigated usage of the recognition
      heuristic have confounded recognition with other cues that could also lead to
      similar judgments. This paper tests whether mere recognition is actually driving
      the findings in support of the recognition heuristic. Two studies provide
      evidence that judgments do not conform to the recognition heuristic when these
      confounds are accounted for. Implications for the study of simple heuristics are
      discussed.

PMID- 14597273
TI  - Using PCR for unraveling the cryptic epizootiology of livestock trypanosomosis in
      the Pantanal, Brazil.
AB  - Trypanosoma vivax and Trypanosoma evansi are livestock parasites of economic
      importance in Africa, Asia and South America. In the Pantanal, Brazil, they cause
      economic losses in both cattle and equines. Little is known of their maintenance
      and spread in nature, particularly in terms of reservoirs and means of mechanical
      transmission. Here we report for the first time the use of PCR for the detection
      of T. vivax and T. evansi in bovines, buffaloes and sheep. Whereas
      parasitological diagnosis detected only two T. vivax infections, one in buffalo
      and another in a cow, PCR detected infections in 34.8% buffaloes, 44.7% bovines
      and 37.3% sheep. Trypanozoon primers detected 41.8% infections in buffaloes and
      8.1% in cattle. PCR revealed 6.9% mixed infections in buffaloes and 5.3% in
      cattle. The potential role of cattle and buffaloes as hosts and reservoirs of T.
      vivax is discussed, as well as the implications of possible extravascular foci in
      the maintenance of livestock trypanosomosis.

PMID- 14597274
TI  - Survey of ovine and caprine toxoplasmosis by IFAT and PCR assays in Sardinia,
      Italy.
AB  - During the period 1999-2002, we have analyzed 9639 serum samples and 815 aborted
      samples (670 fetuses and 145 placenta) from 964 ovine and caprine farms
      distributed over all Sardinia island. After abortion notification, sera collected
      at random from adult animals were examined to detect simultaneously IgG and IgM
      antibodies specific to Toxoplasma gondii by indirect immunofluorescence assay,
      whereas fetuses and placenta were analyzed by a single tube nested PCR assay.
      Specific IgG antibodies were detected in 2048 (28.4%) sheep and 302 (12.3%)
      goats, specific IgM antibodies were found in 652 (9%) sheep and 139 (5.6%) goats.
      From a total of 2471 ovine and 362 caprine fetal samples including muscle, liver,
      abomasum, spleen, brain and placenta, 271 (11.1%) ovine and 23 (6.4%) caprine
      samples were T. gondii PCR-positive. Although T. gondii DNA was amplified from
      different types of tissues, placenta was the tissue with the highest detection
      rate. On the one hand, these results indicate that the seroprevalence of T.
      gondii infection in sheep and goats is relatively high, on the other PCR results
      demonstrate that T. gondii has a significant role in ovine and caprine abortion.
      Adequate management might be useful and essential to control the toxoplasmosis in
      the sheep and goats herds of Sardinia.

PMID- 14597275
TI  - Prevalence of Echinococcus multilocularis in the red fox (Vulpes vulpes) in
      southern Belgium.
AB  - Between June 1998 and February 2002, 709 red foxes killed in Wallonia (south of
      Belgium) were available for parasitological examination of the gut. The
      identification of Echinococcus multilocularis was based on morphological data. E.
      multilocularis adults were observed in 20.2% of the animals. The analysis of data
      revealed marked differences between the geological areas of Wallonia; the highest
      prevalence (33%) was found in the Ardenne and the lowest (0%) on the Plateau de
      Herve. Host gender and the collection season had no effect on the prevalence.
      However, the latter was significantly higher in juveniles (<8 months of age). The
      geographical distribution of E. multilocularis in Belgium is much wider than
      originally thought.

PMID- 14597276
TI  - The musk rat (Ondatra zibethicus) as intermediate host of cestodes in the
      Netherlands.
AB  - An investigation on the presence of larval cestodes in musk rats (Ondatra
      zibethicus) was carried out in two regions of the Netherlands (east Groningen and
      south Limburg) where in a earlier study foxes with Echinococcus multilocularis
      were found. A total of 1726 musk rats were dissected (1200 in Groningen, 526 in
      Limburg). Larval stages of Taenia taeniaeformis were most frequently found (total
      44.8%: Groningen 42%, Limburg 51.3%), followed by T. martis (total 6.1%:
      Groningen 0.7%, Limburg 18.6%). Infections with T. crassiceps (total 0.3%:
      Groningen 0%, Limburg 1.0%), T. polyacantha (total 0.2%; Groningen 0.3%, Limburg
      0%) and E. multilocularis (0.1%: Groningen 0.1%, Limburg 0%) were rare.
      Infections with T. taeniaeformis were more frequent in adults (71.8%) than in
      juveniles (34.2%). The same was found for T. martis: adults 15.3%, juveniles
      2.5%. This difference was also reflected in the relation between weight of the
      animals and presence of infection. Heavier animals (>1000 g) were more often
      infected with T. taeniaeformis (74.1%) than animals less than 1000 g (34.8%). In
      musk rats weighing less than 500 g (n=155) only 5.2% were infected, but above
      1200 g, 82.6%. The highest number of T. taeniaeformis was 28, of T. martis 13, of
      T. crassiceps >1000 and of T. polyacantha 24. The E. multilocularis was in a very
      young stage, a few white spots in the liver. Although E. multilocularis
      infections were exceptional, it is expected that with a rise in the number of
      infected foxes in the Netherlands the number of infected musk rats will increase.

PMID- 14597277
TI  - Field evaluation of a coproantigen enzyme-linked immunosorbent assay for
      diagnosis of canine echinococcosis in a rural Andean village in Peru.
AB  - One hundred and six dogs (61 males and 45 females) were examined for Echinococcus
      granulosus infection in a farming cooperative in the central highlands of Peru
      during November 1998. Canine echinococcosis was diagnosed using direct
      microscopic examinations of purged feces following arecoline purging and a
      coproantigen-detection enzyme-linked immunosorbent assay (ELISA) for E.
      granulosus. Mean age was 2 years with a range of 3 months to 9 years. The overall
      prevalence of canine echinococcosis using the ELISA test was 79% (84/106).
      Seventy-four dogs were successfully purged with arecoline. The frequency of
      canine echinococcosis was 82 (61/74) and 34% (25/74) by the coproantigen ELISA
      test and arecoline purging, respectively. The sensitivity and specificity of the
      coproantigen ELISA test was 88 and 95%, respectively. We found this assay to be
      especially advantageous in remote geographical areas. In future control programs
      against echinococcosis in Peru and other areas where E. granulosus is endemic the
      coproantigen ELISA should be used for the surveillance of the dog population.

PMID- 14597278
TI  - Ovicidal and larvicidal activity in vitro of Spigelia anthelmia Linn. extracts on
      Haemonchus contortus.
AB  - The rapid development of anthelmintic resistance, associated with the high cost
      of the available anthelmintic drugs, had limited the success of gastrointestinal
      nematodiasis control in sheep and goats and thus awakened interest in the study
      of medicinal plants as alternative sources of anthelmintics. Spigelia anthelmia
      extracts obtained with hexane, chloroform, ethyl acetate or methanol, were tested
      on Haemonchus contortus eggs and larvae via egg hatch and larval development
      tests. The extracts were evaluated at five concentrations: 3.1, 6.2, 12.5, 25.0
      and 50.0 mg ml(-1). At 50.0 mg ml(-1), the ethyl acetate extract inhibited 100%
      of the egg hatching and 81.2% of the larval development. In a similar way the
      methanolic extract inhibited 97.4% of the egg hatching and 84.4% of larval
      development. These results suggest that utilization of S. anthelmia extracts may
      be useful in the control of sheep and goats gastrointestinal nematodes.

PMID- 14597279
TI  - The anthelmintic efficacy of five plant products against gastrointestinal
      trichostrongylids in artificially infected lambs.
AB  - Forty-eight helminth-free lambs were divided into eight groups (A-H) of six
      animals. Groups A-G were infected artificially with 10,000 third stage larvae of
      Haemonchus contortus and 20,000 third stage larvae of Trichostrongylus
      colubriformis, whereas group H remained uninfected. Thirty days post-infection
      the lambs were treated orally with a single dosage of one of the following
      products: group A with 3 mg/kg body weight (BW) of an aqueous ethanol extract
      (70%, v/v) of the seeds of Azadirachta indica A. Juss syn. Melia azedarach L.
      (Meliaceae); group B with 1 g/kg BW of a raw powder of the leaves of Ananas
      comosus (L.) Merr. (Bromeliaceae); group C with 0.3 mg/kg BW of an aqueous
      ethanol extract of a 1:1 mixture (g/g) of Vernonia anthelmintica (L.) Willd.
      (Asteraceae) seeds and Embelia ribes Burm (Myrsinaceae) fruits; group D with 183
      mg/kg BW of an aqueous ethanol extract of the whole plants of Fumaria parviflora
      Lam. (Fumariaceae); group E with 28 mg/kg BW of an aqueous ethanol extract of the
      seeds of Caesalpinia crista L. (Caesalpiniaceae); group F with 25 mg/kg BW of
      pyrantel tartrate and group G with 50% ethanol. Group H remained untreated. Only
      the ethanol extract of F. parviflora caused a strong reduction of the faecal egg
      counts (100%) and a 78.2 and 88.8% reduction of adult H. contortus and T.
      colubriformis on day 13 post-treatment. The extract was as effective as the
      reference compound pyrantel tartrate. Therefore, the ethanol extract itself or
      single constituents of F. parviflora could be a promising alternative source of
      anthelmintic for the treatment of gastrointestinal trichostrongylids in small
      ruminants.

PMID- 14597280
TI  - A survey of anthelmintic resistant nematode parasites in Scottish sheep flocks.
AB  - The state of anthelmintic resistance in Scottish sheep flocks was evaluated
      during April-August 2000 using in vitro bioassays, egg hatch assays for detecting
      thiabendazole (TBZ) resistance and larval development assays for levamisole,
      ivermectin and TBZ resistance. Anaerobic sampling kits and detailed
      questionnaires outlining farm demographics and current management practices were
      mailed to 227 Moredun Foundation member farms, replies were received from 98
      farms. Kits received from 90 farms contained sufficient material to conduct one
      or more of the assays. A majority of the farms examined (64%) exhibited TBZ
      resistance but there were both farm locality and regional variations in the
      percentage of resistant farms. Teladorsagia was the predominant genera detected
      from farms. No resistance to levamisole or ivermectin was detected in any of the
      samples. There was no strong evidence from this survey that any of the management
      practices examined greatly affected TBZ resistance.

PMID- 14597281
TI  - Immunological role of the endosymbionts of Dirofilaria immitis: the Wolbachia
      surface protein activates canine neutrophils with production of IL-8.
AB  - Filarial nematodes, including Dirofilaria immitis and D. repens, harbour
      intracellular bacteria belonging to the genus Wolbachia. These bacteria have been
      implicated in the pathogenesis of filarial diseases, possibly through their
      endotoxins. Recent studies have shown that a major surface protein of Wolbachia
      (WSP) induces a specific IgG response in hosts infected by D. immitis. WSP from
      the Wolbachia of D. immitis was produced in recombinant form. The purified
      protein was used in stimulation assays on canine neutrophils. The assays
      performed using a modified Boyden chamber showed that WSP stimulates neutrophil
      chemokinesis. In addition, RT-PCR revealed increased production of chemokine IL-8
      by cells incubated with this protein. Neutrophils have been shown to play a major
      role in the pathogenesis of river blindness, and to accumulate in the nodules of
      onchocerciasis patients. In dogs infected by D. immitis, neutrophils accumulate
      in kidneys and in the wall of pulmonary arteries. As shown by our studies,
      Wolbachia could contribute to these inflammatory phenomena through its surface
      protein WSP, independently from its endotoxin component.

PMID- 14597282
TI  - Polyunsaturated fatty acids and parasitism: effect of a diet supplemented with
      fish oil on the course of rat trichinellosis.
AB  - Dietary fish oil has a beneficial effect on heart and some bacterial diseases and
      apart from other effects, some studies have revealed their ability to modulate
      the course of inflammatory and autoimmune diseases. The study here reported was
      designed to evaluate the possible influence of a fish oil supplement on the
      course of a Trichinella infection. Nutritional, parasitological and immunological
      parameters were analyzed. Two groups of 20 Wistar rats, one fed a standard diet
      and the other one a standard diet supplemented with fish oil, were infected with
      1000 L1 larvae. Other two uninfected groups served as control. Results were as
      follows: fish oil diet intake and infection have, respectively, a positive and a
      negative effect on growth and food utilization. The negative effect is detected
      later in animals fed the fish oil diet. A reduction of 30.9 and 36.6% in the
      number of adult worms and L1 larvae, respectively, was observed in the fish oil
      group as compared to the standard diet group. Production of IFNgamma (Th1
      response) and IL4 (Th2) response was measured in stimulated splenic cells. The
      fish oil diet increased both IFNgamma and IL4 levels. At 6 days after infection
      both IFNgamma and IL4 responses were detected, but at 36 days after infection
      only IL4 was detected in the standard group. The level of somatic and cuticular
      antibodies was not affected by the diet.

PMID- 14597283
TI  - Seasonal translation of infective larvae of gastrointestinal nematodes of cattle
      and the effect of Duddingtonia flagrans: a 3-year pilot study.
AB  - A study was conducted over 3 years (1998-2000) to investigate larval availability
      of gastrointestinal nematodes from faeces of cattle reared under different
      parasite control schemes. These cattle were part of a parallel, but separate
      grazing trial, and were used as donor animals for the faecal material used in
      this experiment. At monthly intervals, faeces were collected and pooled from
      three groups of first-season grazing cattle. These groups were either untreated,
      ivermectin bolus treated or fed the nematophagous fungus Duddingtonia flagrans.
      The untreated and fungus treated animals were infected with gastrointestinal
      nematodes and the number of eggs per gram (epg) pooled faeces ranged between 50
      and 700 in the untreated group and between 25 and 525 epg in the fungus treated
      group. Each year between June and September, artificial 1 kg dung pats were
      prepared and deposited on pasture and protected from birds. The same treatments,
      deposition times and locations were repeated throughout the study. Larval
      recovery from herbage of an entire circular area surrounding the dung pats was
      made in a sequential fashion. This was achieved by clipping samples in replicate
      1/4 sectors around the dung pats 4, 6, 8 and 10 weeks after deposition. In
      addition, coinciding with the usual time of livestock turn-out in early May of
      the following year, grass samples were taken from a circular area centred where
      the dung pats had been located to estimate the number of overwintered larvae,
      which had not been harvested during the intensive grass sampling the previous
      year. It was found that recovery and number of infective larvae varied
      considerably within and between seasons. Although the faecal egg counts in 1999
      never exceeded 300 epg of the faecal pats derived from the untreated animals, the
      abnormally dry conditions of this year generated the highest level of
      overwintered larvae found on herbage in early May 2000, for the 3 years of the
      study. Overall, biological control with D. flagrans significantly reduced larval
      availability on herbage, both during and between the grazing seasons, when
      compared with the untreated control. However, the fungus did not significantly
      reduce overwintered larvae derived from early season depositions (June and July),
      particularly when dung pats disappeared within 2 weeks after deposition. Very low
      number of larvae (<3 per kg dry herbage) were sporadically recovered from grass
      samples surrounding the ivermectin bolus faecal pats.

PMID- 14597284
TI  - Concomitant exposure of rainbow trout fry to Gyrodactylus derjavini and
      Flavobacterium psychrophilum: effects on infection and mortality of host.
AB  - Although rainbow trout fry mortality syndrome caused by the bacterium
      Flavobacterium psychrophilum is widespread in fish farms it is difficult to
      reproduce infection of rainbow trout in the laboratory using immersion exposure
      with bacterial suspensions. It has therefore been speculated that ectoparasites
      could act as enhancers of bacterial infections under natural conditions. In the
      present study rainbow trout fry were exposed to infections with F. psychrophilum
      (immersion for 30 min or 10 h) alone, exposed to the ectoparasitic monogenean
      Gyrodactylus derjavini alone or exposed to both pathogens in combination.
      Infection levels and host mortality were subsequently monitored to elucidate if
      the ectoparasitic monogeneans could enhance infection of fish with the bacterium.
      Immersion of fish in bacterial suspensions alone did not result in infection.
      Only one fish became infected with the bacterium and this fish belonged to the
      combination exposure group. The parasite populations increased differently in the
      various groups and it was found that host mortality was correlated to
      gyrodactylid infection levels (r=0.94) but not to bacterial exposure. The results
      emphasise the pathogenicity of the parasite G. derjavini, the relative resistance
      of intact fish to direct exposure to F. psychrophilum but provide only a weak
      indication of a possible enhancement of bacterial invasion due to ectoparasitic
      infections. It cannot be excluded that higher parasite burdens and/or prolonged
      immersion (more than 10 h) in bacterial suspensions may result in bacterial
      invasion.

PMID- 14597285
TI  - Molecular characterization of a Babesia gibsoni isolate from a Spanish dog.
AB  - Babesia gibsoni is a morphologically small Babesia species that infects dogs.
      Molecular techniques have shown that some small Babesia sp. recently described in
      canids are not related to the original B. gibsoni and they should be assigned to
      separate taxons. Although the 18s rRNA gene of true B. gibsoni isolates has been
      studied in the USA, Asia and Australia, no molecular data on the presence and
      genetic characteristics of B. gibsoni in Europe are available. Blood collected
      from a Babesia-symptomatic dog from Spain was used for DNA diagnosis by
      seminested PCR. DNA amplification was positive and the complete 18s rRNA gene of
      the dog isolate was sequenced, showing 98% homology with B. gibsoni (isolate Asia
      1). Evidence from phylogenetic analysis indicated that: The Spanish isolate
      unambiguously belongs to the B. gibsoni group. The B. gibsoni complex might be
      diphyletic. In the absence of genetic data from African isolates of B. gibsoni,
      Asia seems to be the most likely geographical location of origin.

PMID- 14597286
TI  - Efficacy trial of an irradiated cattle lungworm vaccine in red deer (Cervus
      elaphus).
AB  - Lungworm (Dictyocaulus sp.) is the parasite of most concern to the New Zealand
      deer industry. Although lungworm can be controlled by anthelmintics there is an
      increasing concern over excessive drenching programmes and reliance on chemicals
      for parasite control. A live irradiated larval vaccine developed for cattle has
      been available in Europe for the past 40 years but has never been evaluated in
      red deer in New Zealand. Four groups of red deer and two of cattle were hand
      reared from birth in parasite-free conditions. The cattle acted as a control
      group to ensure that the vaccine was still efficacious on arrival in New Zealand.
      Two groups of deer were vaccinated, and all four groups were challenged with
      either D. viviparus or deer origin Dictyocaulus, tentatively identified as D.
      eckerti. The vaccine provided excellent protection to cattle under New Zealand
      conditions, there was no larval output in the vaccinated cattle and no adults
      were found in their lungs at necropsy. In red deer, patency was delayed in the
      vaccinated groups regardless of challenge species and larval output was lower but
      was not prevented. Adult lungworms were found in the lungs of all deer at
      necropsy but fewer were recorded in the vaccinated deer. Although Huskvac
      provided a degree of protection for red deer it was not effective enough to
      recommend its use.

PMID- 14597287
TI  - Molecular assay for the identification of Setaria tundra.
AB  - We report the molecular characterization of the amplification products obtained
      by specific PCR experiments aimed to identify the 5S ribosomal spacer of Setaria
      tundra specimens isolated from roe deer (Capreolus capreolus) in north Italy,
      which represent the first record of the parasite in this country. Three different
      fragments of approximately 400, 800, and 1200 bp (base pairs) are produced.
      Sequence analyses showed that all three fragments share a very high level of
      similarity to 5S spacer sequences of some Setaria species and other filariae
      present in genebank. Based on these sequences, we were able to design species
      specific PCR primers for the precise identification of S. tundra.

PMID- 14597288
TI  - Efficacy of different dosages of ivermectin injectable against the Hypoderma spp.
      in yaks.
AB  - A chemotherapy trial was conducted to determine the lowest dosage of injectable
      preparation of ivermectin against Hypoderma spp. infestation in yaks in Tibetan
      areas in Tianzhu county, Gansu province, in northwest of China. One hundred and
      sixty yaks were randomly divided into four groups of 40 yaks for the trial. The
      first three groups were treated by subcutaneous injection in the neck with 0.1%
      ivermectin (respectively, 1, 5, 10 microg/kg body weight). The fourth group was
      not treated and considered as control group. All the experiments were performed
      in November 2000 and the animals were examined for the presence of warbles in the
      next March and May. The results indicated that there was no warbles found on the
      back of treated animal while third stage larvae were palpated on back of some of
      the yaks in control group. It is concluded that dosage of 1 microg/kg ivermectin
      injectable was sufficient to kill or stop development of larvae of Hypoderma spp.
      in naturally infected yaks if administrated in November.

PMID- 14597289
TI  - Pharmacokinetics of ivermectin in the yak (Bos grunniens).
AB  - The yak (Bos grunniens) belongs to the cattle family Bovidae and lives in the
      mountains of China and adjacent areas. Due to the physiological adaptations of
      yak to its environment and the lack of data, the ivermectin pharmacokinetic was
      studied following a single subcutaneous dose at the recommended dose for cattle
      (0.2 mg kg(-1)). The observed peak plasma concentration (Cmax) was 48.93 ng ml(
      1) and the time to reach Cmax (Tmax) was 0.73 day. These results show a faster
      rate of absorption than in cattle. The values for the absorption half-life
      (t(1/2a)), the distribution half-life (t(1/2alpha)) and the terminal half-life
      (t(1/2beta)) were 0.31, 0.74 and 4.82 days, respectively. The calculated area
      under the concentration-time curve (AUC) was 146.2 ng day ml(-1) and the mean
      residence time (MRT) was 3.57 days. The availability of ivermectin appears low in
      yaks in comparison to cattle but equivalent to that reported in horses and is
      likely to be due to physiological characteristics of this species.

PMID- 14597290
TI  - Remarks on this special issue.

PMID- 14597291
TI  - Cerebral localization, then and now.
AB  - We review some of the progress made in understanding the nature of functional
      specialization in the human brain, beginning with the anatomical claim that all
      mental faculties have their own distinct material substrate in different regions
      of the brain and the psychological claim that each mental faculty is
      characterized by the content domain with which it deals. This conceptual
      framework led behavioral neurologists to show how discrete brain lesions provoked
      different types of language, praxic, gnostic, spatial, and memory disorders. The
      simplest way of interpreting these anatomoclinical associations was to conjecture
      that the normal function (now impaired by brain damage) was localized within that
      lesioned region. It was also realized that cognitive impairments could arise from
      lesions that spared the functional centers themselves but disconnected them from
      other centers. Nonetheless, many neuroscientists remained skeptical of the entire
      paradigm. Accordingly, in the late 19th century functional localization began to
      be studied in the intact human brain by such techniques as measuring the
      temperature of different brain regions when different cognitive tasks were
      performed. During the 20th century these crude techniques gave way to positron
      emission tomography, functional magnetic resonance imaging, and
      magnetoencephalography. The relatively precise spatial and temporal resolution of
      modern methods now raises a crucial question: Do the functional localizations
      obtained by the anatomoclinical method converge with those implied by the
      functional neuroimaging of cognition in healthy volunteers? We then conclude with
      some recent suggestions that functional specialization is not such a fixed
      property of brain regions as previously supposed.

PMID- 14597292
TI  - The brain basis of syntactic processes: functional imaging and lesion studies.
AB  - Language comprehension can be subdivided into three processing steps: initial
      structure building, semantic integration, and late syntactic integration. The two
      syntactic processing phases are correlated with two distinct components in the
      event-related brain potential, namely an early left anterior negativity (ELAN)
      and a late centroparietal positivity (P600). Moreover, ERP findings from healthy
      adults suggest that early structure-building processes as reflected by the ELAN
      are independent of semantic processes. fMRI results have revealed that semantic
      and syntactic processes are supported by separable temporofrontal networks, with
      the syntactic processes involving the left superior temporal gyrus (STG), the
      left frontal operculum, and the basal ganglia (BG) in particular. MEG data from
      healthy adults have indicated that the left anterior temporal region and the left
      inferior frontal region subserve the early structure building processes. ERP data
      from patients with lesions in the left anterior temporal region and from patients
      with lesions in the left inferior frontal gyrus support this view, as these
      patients do not demonstrate an ELAN, although they do demonstrate a P600. Further
      results from patients with BG dysfunction suggest that parts of this subcortical
      structure are involved in late syntactic integrational processes. The data from
      the different experiments lead to the notion of separable brain systems
      responsible for early and late syntactic processes, with the former being
      subserved by the inferior frontal gyrus and the anterior STG and the latter being
      supported by the BG and more posterior portions of the STG.

PMID- 14597293
TI  - How the brain solves the binding problem for language: a neurocomputational model
      of syntactic processing.
AB  - Syntax is one of the components in the architecture of language processing that
      allows the listener/reader to bind single-word information into a unified
      interpretation of multiword utterances. This paper discusses ERP effects that
      have been observed in relation to syntactic processing. The fact that these
      effects differ from the semantic N400 indicates that the brain honors the
      distinction between semantic and syntactic binding operations. Two models of
      syntactic processing attempt to account for syntax-related ERP effects. One type
      of model is serial, with a first phase that is purely syntactic in nature (syntax
      first model). The other type of model is parallel and assumes that information
      immediately guides the interpretation process once it becomes available. This is
      referred to as the immediacy model. ERP evidence is presented in support of the
      latter model. Next, an explicit computational model is proposed to explain the
      ERP data. This Unification Model assumes that syntactic frames are stored in
      memory and retrieved on the basis of the spoken or written word form input. The
      syntactic frames associated with the individual lexical items are unified by a
      dynamic binding process into a structural representation that spans the whole
      utterance. On the basis of a meta-analysis of imaging studies on syntax, it is
      argued that the left posterior inferior frontal cortex is involved in binding
      syntactic frames together, whereas the left superior temporal cortex is involved
      in retrieval of the syntactic frames stored in memory. Lesion data that support
      the involvement of this left frontotemporal network in syntactic processing are
      discussed.

PMID- 14597294
TI  - Normal and pathological reading: converging data from lesion and imaging studies.
AB  - In this paper we discuss cognitive and anatomical models of reading that have
      emerged from behavioral and lesion studies of dyslexia and functional
      neuroimaging studies of normal subjects. We then suggest that discrepancies in
      their findings can partly be overcome by functional neuroimaging studies of
      patients with acquired dyslexia. We present two such studies. One patient had a
      large left temporoparietal lesion which limited his reading to words with high
      semantic associations. When he read these words aloud, activation was observed in
      all areas of the normal reading system with the exception of the damaged left
      superior temporal lobe. The second patient had anterior temporal lobe atrophy
      with semantic dementia and a deficit in reading words that rely on lexical or
      semantic mediation. When asked to read aloud words on which she was likely to
      succeed, she activated all the normal areas, with increased activation in a left
      sensorimotor area associated with phonological processing and decreased
      activation in several areas associated with semantic processing. By relating
      these findings to those from lesion studies and imaging studies of normals, we
      propose that the translation of orthography to phonology is mediated semantically
      by the anterior part of the left midfusiform gyrus. In contrast, when semantic
      processing is compromised, the translation of orthography to phonology will be
      more reliant on the posterior part of the left midfusiform and the left frontal
      areas associated with phonology. Future studies are required to examine the
      connectivity between these areas during normal and abnormal reading.

PMID- 14597295
TI  - Disturbance and recovery of language function: correlates in PET activation
      studies.
AB  - Disturbance of neurologic function in disorders of the central nervous system is
      expressed as an altered activation pattern in functional networks employed by
      specific tasks and can be studied by functional imaging modalities, e.g.,
      positron emission tomography. Language, a complex brain function, is based on the
      interplay of a distributed network in which partial functions are executed in
      various centers, the primary language areas. These areas are hierarchically
      organized and activated according to the complexity of the specific language
      task. The specialization of different centers and the lateralization of
      integrative functions into the dominant (usually left) hemisphere are achieved by
      collateral and transcallosal inhibition of secondary language areas which
      normally are not employed for performance of a specific language task.

PMID- 14597296
TI  - Within-task switching in the verbal domain.
AB  - Task-switching, a term that covers a wide range of different cognitive processes,
      is a topic of considerable current interest. We draw particular attention to
      verbal within-task switching in neurological patients and healthy volunteers. The
      paradigm employs two types of fluency tasks: (i) semantic category verbal fluency
      in which subjects covertly produce words from a predefined superordinate semantic
      category and (ii) automatic speech tasks in which subjects produce words from
      overlearned sequences. In the single-category conditions, words are produced from
      one category at a time; in the switching conditions, words are produced
      alternately from three categories. For example, the semantic categories could be
      fruits, cars, and furniture and the automatic categories could be days of the
      week, letters of the alphabet, and months of the year. In a previous fMRI study
      of healthy volunteers, the main group effect of switching (semantic category and
      automatic speech) relative to single-category fluency (semantic category and
      automatic speech) showed significant activations (p < 0.05 corrected) only in
      bilateral superior posterior parietal cortex, Brain 125, 1024-1038). There was no
      significant prefrontal activation as a main effect of switching. In this paper we
      present further results from that experiment which show a surprising lack of
      consistent frontal lobe switch activations in single-subject analyses. These
      findings are discussed in relation to other neuroimaging studies of task
      switching and the role of convergent neuropsychological data from patients with
      neurodegenerative disease.

PMID- 14597297
TI  - Neural mechanisms associated with attention to temporal synchrony versus spatial
      orientation: an fMRI study.
AB  - Previous neuropsychological and functional imaging studies have suggested that
      the right hemisphere is crucially involved in spatial cognition. By contrast,
      much less is known about the putative left hemisphere specialization for aspects
      of temporal cognition. Accordingly, we studied with functional magnetic resonance
      imaging the neural mechanisms underlying attention to stimulus onset synchrony or
      orientational congruence with identical pairs of geometric figures. In each
      trial, two rhombuses were presented, each 4 degrees peripheral to a central
      fixation cross, in the left and right visual hemifields. In half of the trials,
      subjects were asked to judge and indicate via button presses whether the
      rhombuses appeared simultaneously. In the other half of the trials, subjects
      indicated whether the orientation of the rhombuses was the same (Factor 1, task,
      temporal synchrony, orientation). In half of the trials, subjects responded with
      their right hand and in the other half with their left hand (Factor 2, hand,
      right, left). Data were analyzed using SPM99 and a random-effects model.
      Attention to orientation differentially activated right temporo-occipital cortex.
      Attention to stimulus onset synchrony activated left anterior superior temporal
      gyrus, left inferior parietal cortex, left medial frontal gyrus, and right
      operculum. Activation of right temporo-occipital cortex for attention to stimulus
      orientation is in good agreement with previous functional neuroimaging studies of
      stimulus orientation. More importantly, activation of a predominantly left
      hemispheric network with attention to stimulus onset synchrony extends the
      results of previous functional imaging, psychophysical, and neuropsychological
      studies of temporal processing.

PMID- 14597298
TI  - Unilateral hemispheric lesions disrupt parallel processing within the
      contralateral intact hemisphere: an auditory fMRI study.
AB  - Evidence from activation studies suggests that sound recognition and localization
      are processed in two distinct cortical networks that are each present in both
      hemispheres. Sound recognition and/or localization may, however, be disrupted by
      purely unilateral damage, suggesting that processing within one hemisphere may
      not be sufficient or may be disturbed by the contralateral lesion. Sound
      recognition and localization were investigated psychophysically and using fMRI in
      patients with unilateral right hemisphere lesions. Two patients had a combined
      deficit in sound recognition and sound localization, two a selective deficit in
      sound localization, one a selective deficit in sound recognition, and two normal
      performance in both tasks. The overall level of activation in the intact left
      hemisphere of the patients was smaller than in normal control subjects,
      irrespective of whether the patient's performance in the psychophysical tasks was
      impaired. Despite this overall decrease in activation strength, patients with
      normal performance still exhibited activation patterns similar to those of the
      control subjects in the recognition and localization tasks, indicating that the
      specialized brain networks subserving sound recognition and sound localization in
      normal subjects were also activated in the patients with normal performance,
      albeit to an altogether lesser degree. In patients with deficient performance, on
      the other hand, the activation patterns during the sound recognition and
      localization tasks were severely reduced, comprising fewer and partly atypical
      activation foci compared to the normal subjects. This indicates that impaired
      psychophysical performance correlates with a breakdown of parallel processing
      within specialized networks in the contralesional hemisphere.

PMID- 14597299
TI  - Right parietal lesions, unilateral spatial neglect, and the egocentric frame of
      reference.
AB  - Recently, the hypothesis has been proposed that the crucial mechanism leading to
      neglect is the disturbed transformation of sensory input into a supramodal
      egocentric frame of reference (ER), which causes in turn a deviation of this
      reference frame toward the side ipsilateral to the brain lesion. This egocentric
      coordinate system is normally centered on the midsagittal plane, but a unilateral
      brain lesion may cause a deviation of the egocentric reference due to an
      imbalance between the differentially lateralized neural processes which build
      this representation. Although neglect signs are often defined in an egocentric
      frame, and an ER shift may be observed in some right-brain-damaged patients
      (RBD), I present here several data that rule out any causal link between the
      deviation of the egocentric reference and the presence and/or severity of left
      neglect signs in RBD patients.

PMID- 14597300
TI  - Left inferior parietal cortex integrates time and space during collision
      judgments.
AB  - Left inferior parietal lobe lesions can cause perturbation of the space-time
      plans underlying skilled actions. But does the perceptual integration of
      spatiotemporal information use the same neural substrate or is the role of the
      left inferior parietal cortex restricted to visuomotor transformations? We use
      fMRI and a collision judgment paradigm to examine whether the left inferior
      parietal cortex integrates temporal and spatial variables in situations in which
      no complex action and no visuomotor transformation is required. We used a
      perceptual task in which healthy subjects indicated by simple button presses
      whether two moving objects (of the same or different size) would or would not
      collide with each other. This task of interest was contrasted with a control task
      that employed the same stimuli and identical motor responses but in which the
      size of the two moving objects had to be compared. To assess putative
      differential eye-movement effects both tasks were performed with and without
      central fixation. Analysis of the fMRI data (employing a random-effects model and
      SPM99) showed that collision judgments (relative to size judgments) provoked a
      significant increase in neural activity in the left inferior parietal cortex
      (supramarginal gyrus) only. These results show that left inferior parietal cortex
      is involved in the integration of perceptual spatiotemporal information and thus
      provide a neural correlate for the use of space-time plans (whose perturbation
      can lead to apraxia as originally hypothesized by Liepmann). Furthermore, the
      data suggest that the left supramarginal gyrus combines temporal and spatial
      variables more widely than previously supposed.

PMID- 14597301
TI  - The left parietal and premotor cortices: motor attention and selection.
AB  - It is well established that the premotor cortex has a central role in the
      selection of movements. The role of parts of the parietal cortex in movement
      control has proved more difficult to describe but appears to be related to the
      preparation and the redirection of movements and movement intentions. We have
      referred to some of these processes as motor attention. It has been known since
      the time of William James that covert motor attention can be directed to an
      upcoming movement just as visuospatial attention can be directed to a location in
      space. While some parietal regions, particularly in the right hemisphere, are
      concerned with covert orienting and the redirecting of covert orienting it may be
      useful to consider other parietal regions, in the anterior inferior parietal
      lobule and in the posterior superior parietal lobule, particularly in the left
      hemisphere, as contributing to motor attention. Such parts of the parietal lobe
      are activated in neuroimaging experiments when subjects covertly prepare
      movements or switch intended movements. Lesions or transcranial magnetic
      stimulation (TMS) affect the redirecting of motor attention. The difficulties
      apraxic patients experience when sequencing movements may partly be due to an
      inability to redirect motor attention from one movement to another. The role of
      the premotor cortex in selecting movements is also lateralized to the left
      hemisphere. Damage to left hemisphere movement selection mechanisms may also
      contribute to apraxia. If, however, it remains intact after a stroke then the
      premotor cortex may contribute to the recovery of arm movements. A group of
      patients with unilateral left hemisphere lesions and impaired movements in the
      contralateral right hand was studied. Functional magnetic resonance imaging
      showed that in some cases the premotor cortex in the intact hemisphere was more
      active when the stroke-affected hand was used. TMS in the same area in the same
      patients had the most disruptive effect on movements. In summary, patterns of
      motor impairment and recovery seen after strokes can partly be explained with
      reference to the roles of the parietal and premotor cortices in motor attention
      and selection.

PMID- 14597302
TI  - Pantomime of object use: a challenge to cerebral localization of cognitive
      function.
AB  - The paper illustrates difficulties and insecurities of localizing cognitive
      functions with the example of pantomime of object use. Numerous studies have
      established a particular sensitivity of this task to left brain damage (LBD), but
      there is no agreement as to how components of its cognitive architecture are
      related to the laterality and intrahemispheric location of responsible lesions.
      Apraxia and asymbolia have been suspected to be crucial for explaining the
      vulnerability of pantomime to LBD, but analysis of correlations between
      impairments of pantomime, imitation of gestures, drawing from memory, and
      language in patients with LBD and aphasia suggests that neither of these putative
      deficits can adequately account for the data. It rather appears that pantomime
      taps a central aspect of left hemisphere function which affects performance on a
      great number of otherwise widely different tasks and which is not bound to any
      particular location within the hemisphere. I discuss ways to resolve apparent
      conflicts between this interpretation and the findings of double dissociations
      between pantomime and imitation in clinical case studies and of circumscribed
      left parietal activation during pantomime in functional neuroimaging.

PMID- 14597303
TI  - Illusory movements of the paralyzed limb restore motor cortex activity.
AB  - In humans, limb amputation or brachial plexus avulsion (BPA) often results in
      phantom pain sensation. Actively observing movements made by a substitute of the
      injured limb can reduce phantom pain, Proc. R. Soc. London B Biol. Sci. 263, 377
      386). The neural basis of phantom limb sensation and its amelioration remains
      unclear. Here, we studied the effects of visuomotor training on motor cortex (M1)
      activity in three patients with BPA. Functional magnetic resonance imaging scans
      were obtained before and after an 8-week training program during which patients
      learned to match voluntary "movements" of the phantom limb with prerecorded
      movements of a virtual hand. Before training, phantom limb movements activated
      the contralateral premotor cortex. After training, two subjects showed increased
      activity in the contralateral primary motor area. This change was paralleled by a
      significant reduction in phantom pain. The third subject showed no increase in
      motor cortex activity and no improvement in phantom pain. We suggest that
      successful visuomotor training restores a coherent body image in the M1 region
      and, as a result, directly affects the experience of phantom pain sensation.
      Artificial visual feedback on the movements of the phantom limb may thus "fool"
      the brain and reestablish the original hand/arm cortical representation.

PMID- 14597304
TI  - Preserved verbal memory function in left medial temporal pathology involves
      reorganisation of function to right medial temporal lobe.
AB  - The left hippocampus and related structures mediate verbal memory function. The
      mechanism underlying preserved verbal memory function in patients with left
      hippocampal damage is unknown. Temporal lobe epilepsy, a common disease, is
      frequently the consequence of a characteristic hippocampal pathology termed
      hippocampal sclerosis, which may also affect the amygdala. In this setting,
      mapping the sites of memory function is a vital component of planning for
      surgical treatment for epilepsy. Using event-related functional magnetic
      resonance imaging, we studied 24 right-handed nonamnesic patients with left
      hippocampal sclerosis and 12 normal controls, performing a verbal encoding task.
      The patients were subdivided into two groups according to presence or absence of
      additional left amygdala pathology. Analysis of the data employed a two-level
      random-effects design, examining the main effects of subsequent memory in each
      group, as well as the differences between the groups. Additional effects of
      emotionality of the remembered words were also examined. Verbal memory encoding
      involved activation of left hippocampus in normals, but was associated with
      reorganisation to right hippocampus and parahippocampal gyrus in the patients.
      The additional presence of left amygdala sclerosis resulted in reorganisation for
      encoding of emotional verbal material to right amygdala. Retained verbal memory
      function in the presence of left medial temporal lobe pathology is mediated by
      recruitment of a parallel system in the right hemisphere consistent with adaptive
      functional reorganisation. The findings indicate a high degree of plasticity in
      medial temporal lobe structures.

PMID- 14597305
TI  - Functional-anatomical concepts of human premotor cortex: evidence from fMRI and
      PET studies.

PMID- 14597306
TI  - Psychogenic amnesia.
AB  - Time- and content-based memory systems are briefly described so that their
      importance for a refined analysis of memory disturbances becomes evident. These
      memory systems are then related to their brain instantiation, emphasizing that
      there are limbic circuits for encoding different forms of memories, largely
      cortical networks for memory storage, and a combined temporofrontal network
      acting to trigger information retrieval. The terms functional amnesias and
      psychogenic amnesias are discussed and their symptomatology is compared to that
      of organic amnesias. The term "mnestic block syndrome" is introduced and defined
      as a syndrome of its own. Experimental data, obtained especially with functional
      imaging methods, are presented to elucidate changes in neural activation during
      functional amnesic states. It is concluded that functional amnesic states,
      confined to a patient's biography, can be triggered by environmentally induced
      stress and trauma, leading to lasting inability to retrieve autobiographical
      events. Such an impairment may be identified at the brain level using functional
      imaging techniques.

PMID- 14597307
TI  - Dissecting out conscious and unconscious memory (sub)processes within the human
      medial temporal lobe.
AB  - The human medial temporal lobe (MTL) system mediates memories that can be
      consciously recollected. However, the specific natures of the individual
      contributions of its various subregions to conscious memory processes remain
      equivocal. Here we show a functional dissociation between the hippocampus proper
      and the parahippocampal region in conscious and unconscious memory as revealed by
      invasive recordings of limbic event-related brain potentials recorded during
      explicit and implicit word recognition: Only hippocampal and not parahippocampal
      neural activity exhibits a sensitivity to the implicit versus explicit nature of
      the recognition memory task. Moreover, only within the hippocampus proper do the
      neural responses to repeated words differ not only from those to new words but
      also from each other as a function of recognition success. By contrast
      parahippocampal (rhinal) responses are sensitive to repetition independent of
      conscious recognition. These findings thus demonstrate that it is the hippocampus
      proper among the MTL structures that is specifically engaged during conscious
      memory processes.

PMID- 14597308
TI  - Functional imaging and neuropsychology findings: how can they be linked?
AB  - It is argued that in poorly understood domains functional imaging and
      neuropsychology findings on cognitive processes can be related only through
      functional models of normal cognition. The psychological concept of "resource"
      can, however, be simply extrapolated to functional imaging. It is then argued
      that double dissociations can have analogous inferential power for extrapolation
      to models of normal cognition in functional imaging as in neuropsychology. The
      argument is illustrated by the example of the control processes involved in
      functional episodic memory imaging of experiments.

PMID- 14597309
TI  - Selecting candidate genes from DNA array screens: application to neuroscience.

PMID- 14597310
TI  - Normalization of cDNA microarray data.
AB  - Normalization means to adjust microarray data for effects which arise from
      variation in the technology rather than from biological differences between the
      RNA samples or between the printed probes. This paper describes normalization
      methods based on the fact that dye balance typically varies with spot intensity
      and with spatial position on the array. Print-tip loess normalization provides a
      well-tested general purpose normalization method which has given good results on
      a wide range of arrays. The method may be refined by using quality weights for
      individual spots. The method is best combined with diagnostic plots of the data
      which display the spatial and intensity trends. When diagnostic plots show that
      biases still remain in the data after normalization, further normalization steps
      such as plate-order normalization or scale-normalization between the arrays may
      be undertaken. Composite normalization may be used when control spots are
      available which are known to be not differentially expressed. Variations on loess
      normalization include global loess normalization and two-dimensional
      normalization. Detailed commands are given to implement the normalization
      techniques using freely available software.

PMID- 14597311
TI  - Application of the S-score algorithm for analysis of oligonucleotide microarrays.
AB  - In the past several years, oligonucleotide microarrays have emerged as a widely
      used tool for the simultaneous, non-biased measurement of expression levels for
      thousands of genes. Several challenges exist in successfully utilizing this
      biotechnology; principal among these is analysis of microarray data. An
      experiment to measure differential gene expression can consist of a dozen
      microarrays, each consisting of over a hundred thousand data points. Previously,
      we have described the use of a novel algorithm for analyzing oligonucleotide
      microarrays and assessing changes in gene expression. This algorithm describes
      changes in expression in terms of the statistical significance (S-score) of
      change, which combines signals detected by multiple probe pairs according to an
      error model characteristic of oligonucleotide arrays. Software is available that
      simplifies the use of the application of this algorithm so that it may be applied
      to improving the analysis of oligonucleotide microarray data. The application of
      this method to problems of the central nervous system is discussed.

PMID- 14597312
TI  - Using ANOVA for gene selection from microarray studies of the nervous system.
AB  - Methods are presented for detecting differential expression using statistical
      hypothesis testing methods including analysis of variance (ANOVA). Practicalities
      of experimental design, power, and sample size are discussed. Methods for
      multiple testing correction and their application are described. Instructions for
      running typical analyses are given in the R programming environment. R code and
      the sample data set used to generate the examples are available at
      http://microarray.cpmc.columbia.edu/pavlidis/pub/aovmethods/.

PMID- 14597313
TI  - Selection and validation of microarray candidate genes from subregions and
      subnuclei of the brain.
AB  - DNA array technology now allows an enormous amount of expression data to be
      obtained. For large-scale gene profiling enterprises, this is of course welcome.
      However, the scientist interested in follow-up studies of a handful of
      differentially expressed genes may find it hard to sift through the vast datasets
      to pinpoint genes with the most desirable and reliable behaviors. Here, we
      present the methodology we have employed to discover genes differentially
      expressed in the adult mouse brain. We first used Affymetrix microarrays to
      compare gene expression from five different brain regions: the amygdala,
      cerebellum, hippocampus, olfactory bulb, and periaqueductal gray. Second, we
      identified genes differentially expressed within three distinct amygdala
      subnuclei. In this case, the tissue was microdissected by laser-capture to
      minimize contamination from adjacent subnuclei, and extracted RNA was subjected
      to three rounds of linear amplification prior to hybridization to the
      microarrays. To select candidate genes, we developed a custom algorithm to
      identify those genes with the most robust changes in expression across different
      replicate samples. Confirmation of expression patterns with in situ hybridization
      uncovered further criteria to consider in the selection process.

PMID- 14597314
TI  - Methods for the identification of differentially expressed genes in human post
      mortem brain.
AB  - Microarrays can be used to monitor the expression of thousands of genes
      simultaneously. This technique requires high-quality RNA which can be extracted
      from a variety of tissues and cells including post-mortem human brain. Given the
      vast amount of information obtained from microarray studies, it is critical to
      establish valid analysis techniques to identify differentially expressed genes.
      This technical report describes the basic methodology and analyses used to
      identify such genes in human post-mortem brain tissue.

PMID- 14597315
TI  - Focused microarray analysis.
AB  - We describe detailed protocols and results with an integrated platform for
      studying relative transcript expression, including microarray design and
      fabrication, analysis and calibration algorithms, and high throughput
      quantitative real-time PCR. This approach optimizes sensitivity and accuracy
      while controlling the cost of experiments. A high quality cDNA array was
      fabricated using a restricted number of carefully selected transcripts with each
      clone printed in triplicate. This focused array facilitated both repeated
      measurement and replicate experiments. Following normalization and differential
      expression analysis, we found that experiments with this array identified
      differentially expressed transcripts with a high degree of accuracy and with high
      sensitivity to low levels of differential expression. Using a calibration
      algorithm improved the accuracy of the array in quantifying the relative level of
      transcript expression. All differentially expressed transcripts identified by the
      array were independently tested using high throughput quantitative real-time PCR
      assays. This approach reliably identified transcripts having as low as 1.3-fold
      differences in transcript expression between RNA samples from treatment- and
      control groups and was applicable to highly heterogenous tissue sources such as
      hypothalamus and cerebral cortex.

PMID- 14597316
TI  - Voxelation and gene expression tomography for the acquisition of 3-D gene
      expression maps in the brain.
AB  - Voxelation and gene expression tomography or GET are novel methods for the high
      throughput acquisition of gene expression patterns in the mammalian brain.
      Voxelation employs analysis of spatially registered voxels (cubes), while GET
      employs analysis of sets of parallel slices rotated about multiple independent
      axes of rotation. Both methods employ reconstruction of the data to result in
      multiple volumetric maps of gene expression analogous to those obtained from
      biomedical imaging techniques. Here, we describe the methodologies underlying
      voxelation and GET and briefly outline the insights that can be obtained from
      these approaches.

PMID- 14597317
TI  - Adapter-tagged competitive PCR (ATAC-PCR)--a high-throughput quantitative PCR
      method for microarray validation.
AB  - Adapter-tagged competitive PCR (ATAC-PCR) is an advanced version of competitive
      quantitative PCR that is characterized by the addition of unique adapters to cDNA
      derived from each sample RNA. Using multiple adapters, we can accurately measure
      the relative expression ratios of many samples, with a calibration curve obtained
      from internal standards included in the same reaction. ATAC-PCR can identify
      differences in gene expression as small as twofold, even from very small amounts
      of sample RNA. This technique is suitable for confirming results obtained with
      cDNA microarrays or differential display, and it can process more than a thousand
      of genes per day when used in conjunction with a capillary DNA sequencer.

PMID- 14597319
TI  - Validating FDG-PET as a biomarker for frontotemporal dementia.
AB  - Positron emission tomography with (18)F-fluorodeoxyglucose (FDG-PET) has been
      used to study neurodegenerative disease for the past two decades. This imaging
      method has conclusively demonstrated that dementing diseases are multifocal,
      rather than global, brain disorders and has shown that clinically similar
      dementias may have significantly different patterns of regional glucose
      metabolism. These observations have helped to focus pathological investigations
      and provided new insights into disease pathophysiology, yet the diagnostic
      potential of FDG-PET has not been fully exploited. Now that FDG-PET is becoming
      widely available to clinicians, it is timely to consider how to evaluate its
      utility in diagnosing dementing diseases. FDG-PET may be especially valuable in
      the clinical recognition of frontotemporal dementia (FTD). FTD causes a
      distinctive pattern of cerebral glucose hypometabolism, but can be difficult to
      distinguish clinically from more common disorders such as Alzheimer's disease and
      psychiatric disturbances. Currently available studies primarily evaluate
      metabolic changes in groups of patients and are inadequate to rely upon when
      evaluating individuals. Additional carefully designed clinical trials are needed
      to validate FDG-PET as a diagnostic biomarker.

PMID- 14597320
TI  - Seizure prediction using scalp electroencephalogram.
AB  - Using a measure of nonlinear dynamical changes we term marginal predictability,
      we report evidence of robust changes in this parameter on scalp EEG in a cohort
      of patients with medically refractory mesiobasal temporal lobe epilepsy (MBTLE).
      In the baseline (interictal) state there are distinct differences in this
      nonlinear measure between epileptic and neurologically normal subjects. At
      baseline, in patients with MBTLE there are differences in these measures between
      electrodes adjacent to the ictal onset zone and more remotely placed electrodes.
      The character of these differences evolves over a period of approximately 30 min
      before a seizure. We discuss and integrate our findings with two emerging
      concepts in epileptology, first, the concept of a preictal or transition phase
      rather than an abrupt movement from interictal to ictal activity, and second, the
      notion of an epileptic neural network with changes in areas of brain remote from
      what has traditionally been considered the ictal onset zone influencing
      "ictogenesis."

PMID- 14597321
TI  - Therapeutic gene transfer with herpes-based vectors: studies in Parkinson's
      disease and motor nerve regeneration.
AB  - We have examined the possibility of using herpes simplex virus (HSV)-based
      vectors to prevent neuronal cell death and enhance functional recovery after
      injury. In the 6-hydroxydopamine (6-OHDA) model of Parkinson's disease (PD) and
      after proximal spinal root injury, direct stereotactic injection of HSV-based
      vectors constructed to express the glial cell derived neurotrophic factor (GDNF)
      or the anti-apoptotic peptide Bcl-2 prevented neuronal death and enhanced
      recovery. Gene transfer may be useful in the treatment of neurologic disorders in
      which neuronal cell death occurs in a restricted anatomic distribution.

PMID- 14597322
TI  - Development of HSV-mediated gene transfer for the treatment of chronic pain.
AB  - Chronic pain is often difficult to treat effectively. We have exploited the high
      affinity of herpes simplex virus (HSV) for peripheral sensory neurons to create
      HSV-based vectors for the treatment of chronic pain. We have demonstrated that an
      HSV-based vector expressing proenkephalin reduces pain-related responses in
      rodent models of inflammatory pain, neuropathic pain, and pain resulting from
      cancer in bone. A human trial has been proposed.

PMID- 14597323
TI  - mGluRs: a target for pharmacotherapy in Parkinson disease.
AB  - Metabotropic glutamate receptors (mGluRs) are G-protein-coupled excitatory amino
      acid (glutamate) receptors and are abundantly expressed in basal ganglia nuclei.
      We used behavioral, regional glucose uptake metabolic mapping, and FOS protein
      expression to examine the effects of stimulating striatal and subthalamic mGluRs
      in rats. Stimulation of striatal Group I mGluRs produced behavioral effects
      mediated by polysynaptic activation of subthalamic neurons. Stimulation of
      subthalamic Group II mGluRs produced similar effects. Excessive activity of
      subthalamic neurons is a key feature of parkinsonism. mGluR Group I or Group II
      antagonists may prove to be useful for symptomatic treatment of parkinsonism.
      Stimulation of Group III mGluRs produced behavioral effects in only 6
      hydroxydopamine-lesioned animals. Regional glucose uptake metabolic mapping and
      FOS expression studies suggested that striatal dopamine denervation produced
      increased sensitivity of Group III mGluRs. Agents active at Group III mGluRs may
      also be useful for treatment of parkinsonism.

PMID- 14597325
TI  - Lessons in mentoring.
AB  - Mentoring is an essential catalyst for a successful medical career in science or
      clinical practice. In recent years, tools have been developed to measure the
      impact of mentoring on career achievements, and numerous models have been
      developed to improve mentor training. Sid Gilman, M.D., F.R.C.P., Chair of
      Neurology for 26 years at the University of Michigan, is well-recognized as a
      role model for mentors in neurology across the country. We report the result of a
      survey of his former trainees on the valuable aspects of his mentoring style. A
      review of the current mentoring literature, including suggested training programs
      for mentors, is also provided.

PMID- 14597324
TI  - Injury and plasticity in the developing brain.

PMID- 14597326
TI  - Where's the logic in neurologic education?
AB  - Current practices in neurologic education, and medical education in general, are
      based largely on intuition and tradition rather than empiric evidence.
      Educational practices can and should be rigorously evaluated. The topics to be
      investigated fall into one or more of three broad categories: What should we
      teach? How should we teach it? How do we know what they have learned? This paper
      presents examples of research in each of these categories.

PMID- 14597327
TI  - Counting motor units in chronic motor neuropathies.
AB  - The degree of motor unit loss can not be accurately quantified in chronic motor
      neuropathies with routine electrodiagnostic testing or with pathologic
      examination. We used motor unit number estimation (MUNE), which is a unique
      electrophysiologic method that can estimate the number of surviving motor units
      innervating a muscle, to study axonal loss in spinal muscular atrophy (SMA) and
      Charcot-Marie-Tooth (CMT) neuropathies. MUNE is based on the ratio of the maximal
      compound muscle action potential (CMAP) to the average surface-recorded motor
      unit potential (S-MUP). The hypothenar muscle group was studied in infant and
      older subjects with SMA, and the hypothenar and biceps-brachialis muscle groups
      were studied in adult CMT1A and CMT2 subjects. The multiple point stimulation
      MUNE technique was used in SMA subjects and the spike triggered averaging MUNE
      technique was used in CMT subjects. In SMA, motor unit loss was profound in types
      1 and 2 subjects and more moderate in type 3 subjects. In CMT, motor unit loss
      was prominent in distal muscles in both CMT1A and 2 subjects, and present in
      proximal muscles in CMT2 subjects. MUNE is efficient in assessing the degree of
      motor unit loss in chronic motor neuropathies. SMA is considered to be a proximal
      muscle disorder, but loss was marked in distal muscles in all SMA types. In
      CMT1A, the demyelinating form, motor unit loss was marked in distal muscles,
      consistent with the idea that axonal loss and not slow conduction velocity is the
      important pathologic condition. The pattern of proximal motor unit loss differed
      between CMT1A and 2, suggesting differences in underlying axonal pathology.

PMID- 14597328
TI  - Mutations linked to generalized epilepsy in humans reduce GABA(A) receptor
      current.
AB  - The first mutations of the GABA(A) receptor channel linked to familial epilepsy
      in humans were reported in the gamma2L subunit. When expressed in Xenopus
      oocytes, the gamma2 subunit R43Q mutation abolished current enhancement by the
      benzodiazepine, diazepam, and the gamma2 subunit K289M mutation decreased current
      amplitudes. In this study, single channel recording and concentration jump
      techniques were used to evaluate the effects of these mutations on GABA(A)
      receptor currents from receptors expressed in human embryonic kidney cells. When
      co-expressed with alpha1 and beta3 subunits, the mutated gamma2 subunits did not
      alter current activation rates or rates or extent of desensitization during
      prolonged (400 ms) GABA application (1 mM). Deactivation following brief (5 ms)
      or prolonged (400 ms) GABA application was accelerated for the K289M, but not the
      R43Q mutation. Single channel analysis showed shorter mean open duration,
      suggesting that the faster deactivation was likely caused by altered gating
      efficacy. Interestingly, the R43Q mutation did not alter diazepam potentiation.
      However, significantly smaller current amplitudes were observed that were not
      explained by decreased single channel conductance or open time, suggesting this
      mutation resulted in reduced surface expression of functional receptors. These
      two gamma mutations likely produce disinhibition and familial epilepsy by
      distinct mechanisms, suggesting that maintenance of normal neuronal inhibition
      depends on both the peak amplitude of IPSCs and their time course.

PMID- 14597330
TI  - Insights into the pathophysiology of neuropathic pain through functional brain
      imaging.
AB  - We present here an example case of neuropathic pain with heat allodynia as a
      major symptom to illustrate how the functional imaging of pain may provide new
      insights into the pathophysiology of painful sensory disorders. Tissue injury of
      almost any kind, but especially peripheral or central neural tissue injury, can
      lead to long-lasting spinal and supraspinal re-organization that includes the
      forebrain. These forebrain changes may be adaptive and facilitate functional
      recovery, or they may be maladaptive, preventing or prolonging the painful
      condition, and interfering with treatment. In an experimental model of heat
      allodynia, we used functional brain imaging to show that: (1) the forebrain
      activity during heat allodynia is different from that during normal heat pain,
      and (2) during heat allodynia, specific cortical areas, specifically the
      dorsolateral prefrontal cortex, can attenuate specific components of the pain
      experience, such as affect, by reducing the functional connectivity of
      subcortical pathways. The forebrain of patients with chronic neuropathic pain may
      undergo pathologically induced changes that can impair the clinical response to
      all forms of treatment. Functional imaging, including PET, fMRI, and
      neurophysiological techniques, should help identify brain mechanisms that are
      critical targets for more effective and more specific treatments for chronic,
      neuropathic pain.

PMID- 14597331
TI  - Substrate patterning: an emerging technology for the study of neuronal behavior.
AB  - Extracellular matrix (ECM) proteins and cell-cell adhesion molecules (CAM) play
      important roles in neuronal development and differentiation. In the investigation
      of these roles, patterned substrates have proven to be a notably useful tool.
      Photolithographic and microprinting techniques can be used to make patterns of
      ECMs, CAMs, amino acids, and organofunctional groups for culturing neurons and
      other cell types. Experiments performed using these substrates have provided
      unique insights into the roles of cell-substratum adhesion, cell shape, and ECM
      composition on important cell functions, including survival, migration, neurite
      outgrowth, and development of polarity. Patterns may also be designed to localize
      cell bodies and confine their processes to predetermined areas of a substrate.
      Finally, the behavior of neurons on patterned substrates may prove helpful in the
      design of scaffoldings and nerve guides tailored for regeneration and repair of
      the nervous system.

PMID- 14597329
TI  - Assessment of neuroimaging techniques as biomarkers of the progression of
      Parkinson's disease.
AB  - A major goal of research in Parkinson's disease (PD) has been the development of
      treatments to slow the progressive degeneration of the nigrostriatal dopaminergic
      system and to reduce the functional decline of patients. Because of the
      uncertainty in the ability of the clinical evaluation to reflect the status of
      the nigrostriatal dopaminergic system once dopaminergic therapy has commenced,
      investigators in PD have sought to develop alternative measures of disease. One
      approach, which has been extensively explored, is neuroimaging with radiotracers
      that interact with processes central to dopaminergic neurotransmission in the
      nigrostriatal dopaminergic axons-conversion of levodopa to dopamine through
      aromatic amino acid decarboxylase (AADC), [(18)F]fluorodopa PET, storage of
      dopamine in synaptic vesicles via the vesicular monoamine transporter 2 (VMAT2),
      (+)-[(11)C]dihydrotetrabenazine PET, and reuptake of dopamine into axons via the
      dopamine transporter (DAT), [(123)I]beta-CIT SPECT, and a number of other PET and
      SPECT ligands. During the 54(th) Annual Meeting of the American Academy of
      Neurology, a group of investigators active in the fields of biomakers,
      neuroimaging, and neuroprotection met to review the three techniques mentioned
      above. Prior to the meeting, the participants developed consensus on a set of 10
      criteria for a neuroimaging technique to be considered adequate as a biomarker
      for progression of PD and levels at which the available data for each technique
      indicate that the criterion was met. The criteria and each of the three imaging
      techniques mentioned above were reviewed, and the results of that meeting are
      presented.

PMID- 14597333
TI  - Advances in the hereditary spastic paraplegias.
AB  - This review summarizes advances in understanding the genetics of the hereditary
      spastic paraplegias (HSPs), a diverse group of inherited disorders in which the
      primary symptom is insidiously progressive difficulty walking due to lower
      extremity spastic weakness. Twenty HSP loci and nine HSP genes have been
      discovered. This progress has yielded new insights into the diverse molecular
      pathogenesis that underlies these clinically similar disorders.

PMID- 14597332
TI  - Metabotropic glutamate receptor regulation of neuronal cell death.
AB  - The metabotropic glutamate receptors (mGluRs) are a family of glutamate-sensitive
      receptors that regulate neuronal function separately from the ionotropic
      glutamate receptors. By coupling to guanosine nucleotide-binding proteins (G
      proteins), mGluRs are able to regulate neuronal injury and survival, likely
      through a series of downstream protein kinase and cysteine protease signaling
      pathways that affect mitochondrial regulated programmed cell death (PCD). The
      physiological relevance of this system is supported by evidence that mGluRs are
      associated with cell survival in several central nervous system neurodegenerative
      diseases. Evidence is presented that mGluRs are also able to prevent PCD in the
      peripheral nervous system, and that this may provide a novel mechanism for
      treatment of diabetic neuropathy. In dorsal root ganglion (DRG) neurons, a high
      glucose load increases generation of reactive oxygen species (ROS), destabilizes
      the inner mitochondrial membrane potential (Deltapsi(M)), induces cytochrome c
      release from the mitochondrial intermembrane space, and induces downstream
      activation of caspases. In high-glucose conditions, the group II metabotropic
      glutamate agonist N-acetylaspartylglutamate (NAAG) blocks caspase activation and
      is completely reversed by the mGluR3 antagonist (S)-alpha-ethylglutamic acid
      (EGLU). Furthermore, the direct mGluR3 agonist (2R,4R)-4-aminopyrrolidine-2, 4
      dicarboxylate (APDC) prevents induction of ROS. Together these findings are
      consistent with an emerging concept that mGluRs may protect against cellular
      injury by regulating oxidative stress in the neuron. More complete understanding
      of the complex PCD regulatory pathways mediated by mGluRs will provide new
      therapeutic approaches for the treatment of a wide variety of neurodegenerative
      diseases.

PMID- 14597334
TI  - Parameters of cerebral perfusion in phase-inversion harmonic imaging (PIHI)
      ultrasound examinations.
AB  - The aim was to evaluate phase-inversion harmonic imaging (PIHI) with respect to
      brain perfusion imaging using a novel "bilateral approach" (depth of examination:
      150 mm) and established unilateral approach (100 mm). After bolus injection of
      two contrast agents (CA, Optison and SonoVue), perfusion-related parameters (time
      to-peak intensity, Itpk, peak intensity, Ipk, and peak width, Wpk) were extracted
      by fitting a model function to time-intensity curves for different regions-of
      interest (ROI) in 14 volunteers. In 207 (92%) of 224 ipsilateral ROIs and in 165
      (98%) of 168 contralateral ROIs (372 or 95% of 392 altogether), parameters could
      be derived. Itpk and Wpk of gray matter ROIs did not vary in or between both CA
      groups (18.1-21.9 s and 7.9-14.2 s). ROIs within arteries showed significantly
      shorter Itpk (16.1-16.7 s) and longer Wpk (12.8-28.3 s). Level of significance
      was 0.05 (two-sided). Newer CAs are usable for nonlinear imaging over a wider
      range of acoustic intensities, so that sensitivity of PIHI is sufficient to image
      the brain bilaterally. This approach proves to be reliable in patients with
      adequate bone windows. For acute stroke patients, this implies that both
      hemispheres can be compared in one instead of two examinations, reducing time of
      examination by 50%. Furthermore, evaluation of regions close to the probe becomes
      possible. Thus, the "bilateral approach" should be considered as a new standard
      approach of acute ultrasonic perfusion imaging.

PMID- 14597335
TI  - In vivo breast tumor detection using transient elastography.
AB  - This paper presents first in vivo experiments for breast tumor detection using
      transient elastography. This technique has been developed for detection and
      quantitative mapping of hard lesions in soft tissues. It consists in following
      the propagation inside soft tissues of very low-frequency shear waves
      (approximately 60 Hz) generated by a vibrating system located at the body
      surface. Because transient shear waves propagate through the medium in less than
      0.1 s, the shear propagation imaging is performed with an ultrafast echographic
      scanner able to reach frame rates up to 6000 Hz. The local shear wave speed is
      directly linked to the local shear Young's modulus of the medium. The shear
      elasticity map of the medium can then be computed using an inversion algorithm.
      In vivo experiments were conducted on 15 women who had palpable breast lesions.
      For clinical adaptability reasons, shear waves were generated by the surface of
      the ultrasound (US) imaging transducer itself, which was linked to a mechanical
      vibrator. Our preliminary in vivo results demonstrate the clinical applicability
      of the transient elastography technique for breast lesion detection.

PMID- 14597336
TI  - Noradrenergic constriction of cerebral arteries as detected by transcranial
      Doppler (TCD) in the rabbit.
AB  - Interpretation of transcranial Doppler (TCD) recordings requires assumptions
      about flow or diameter of the insonated vessel. This study aimed at assessing if
      activation of the sympathetic system could affect blood velocity (bv) in basal
      cerebral arteries. In anaesthetized rabbits, stimulation of cervical sympathetic
      nerve (cervSN) was used selectively to activate the sympathetic pathway to the
      head while monitoring bv in all major cerebral arteries. cervSN stimulation at 10
      Hz produced: 1. in internal carotid artery (ICA) and ICA-supplied arteries (ICA
      s), a consistent bv increase ranging between 20 and 70%, 2. in the basilar
      artery, a transient decrease by 15-30%. These effects were mimicked, in both
      territories, by injection of phenylephrine into the ICA. Because cerebral blood
      flow is known to be reduced by cervSN stimulation, the increase in bv in ICA and
      ICA-s must be ascribed to constriction of the insonated vessels. These effects
      should be considered when monitoring bv during sympathetic activation tests or
      exercise.

PMID- 14597337
TI  - Localized harmonic motion imaging: theory, simulations and experiments.
AB  - Several techniques have been developed in an effort to estimate mechanical
      properties of tissues. These techniques typically estimate static or harmonic
      motion resulting from an externally or internally applied mechanical stimulus. In
      this paper, we discuss the advantages of utilizing a new technique that performs
      radiofrequency (RF) signal tracking to estimate the localized oscillatory motion
      resulting from the harmonic radiation force produced by two focused ultrasound
      (US) transducer elements with overlapping beams oscillating at distinct
      frequencies. Finite-element and Monte-Carlo simulations were performed to
      characterize the range of oscillatory displacements produced by a harmonic
      radiation force. In the experimental verification, three transducers were used:
      two single-element focused transducers and one lead zirconate-titanate (PZT)
      composite 16-element probe. Four agar gels were utilized to determine the effect
      of stiffness on the motion amplitude. Estimates of the displacement relative to
      the initial position (i.e., at the onset of the application of the radiation
      force) were obtained during the application of the radiation force that
      oscillated at frequencies ranging between 200 Hz and 800 Hz. In the simulations,
      the estimated oscillatory displacement spanned from -800 to 600 microm and the
      frequencies of excitation could easily be estimated from the temporal variation
      of the displacement. In addition, a frequency upshift (on the order of tens of
      Hz) was estimated with stiffness increase. Furthermore, an exponential decrease
      of the displacement amplitude with stiffness was observed at all frequencies
      investigated. An M-mode version to depict both the spatial and temporal
      variations of the locally induced displacement was used. In experiments with gels
      of different stiffness, the resulting amplitude of the harmonic displacement
      estimated oscillated at the same frequencies and ranged from -300 to 250 microm.
      An exponential decrease of the displacement amplitude with the gel stiffness was
      also observed. In tissue experiments, the results showed that the method is
      feasible in tissues and that focused US surgery (FUS) ablation can be detected.
      These preliminary results demonstrate the feasibility of imaging localized
      harmonic motion as induced by an oscillatory US radiation force. Due to the
      highly localized and harmonic nature of the estimated response, this technique
      may be proven to be highly suitable for simple and accurate estimation of the
      elastic modulus variation in tissues due to disease.

PMID- 14597338
TI  - Effects of aldehyde dehydrogenase genotypes on carotid atherosclerosis.
AB  - Atherosclerotic diseases are thought to be less frequent in Asians compared with
      Caucasians. Unlike Caucasians, nearly half of Asians have a functional deficiency
      in the low Km aldehyde dehydrogenase (ALDH2), a key enzyme in alcohol metabolism,
      which potentially modifies the prevalence of atherosclerosis. This study examined
      the associations between ALDH2 genotypes ("typical homo," "hetero" or "atypical
      homo") and carotid atherosclerosis in 304 Japanese patients. As a measure of
      carotid atherosclerosis, plaque score (PS) was evaluated by B-mode
      ultrasonography. Age- and sex-adjusted PS was lower in "atypical homo" genotype
      patients (2.7 +/- 1.2 [mean +/- standard error], n=21) (p<0.05) and tended to be
      lower in "hetero" patients (4.5 +/- 0.5, n=116) (p=0.07) compared with "typical
      homo" patients (5.7 +/- 0.4, n=167). When we controlled for traditional
      cardiovascular risk factors and alcohol intake, the "atypical homo" genotype was
      found to be associated with lower PS (beta=-0.13, p<0.05). Based on these
      findings, the ALDH2 genotypes seem to be associated with the severity of carotid
      atherosclerosis, potentially modifying the prevalence of atherosclerosis in
      Asians.

PMID- 14597339
TI  - A multivessel model describing replenishment kinetics of ultrasound contrast
      agent for quantification of tissue perfusion.
AB  - To improve the quantification of tissue perfusion using intermittent sonography,
      a new model describing replenishment kinetics of microbubbles is proposed. The
      new approach takes into account the variability of blood flow velocities found in
      vivo, especially in tumors, and consistently describes the refilling process of
      microbubbles. Based upon this model, blood volume, blood velocity, blood flow and
      perfusion in 17 experimental tumors were calculated, and compared with the
      results obtained with the established, phenomenologically derived exponential
      kinetic model. In contrast to the existing model, our approach describes tissue
      vascularization more physiologically and allows deduction of a consistent new
      hyperbolic model for quantification of intermittent sonography. Blood volume and
      mean blood velocity did significantly correlate between both the new and the
      established model (k=0.99; k=0.94, both p<0.001). However, mean tumor blood
      velocity was lower (-19%, p<0.01) with the established model compared to the
      newly developed model. In addition, the range and distribution of blood flow
      velocities found in vivo can be estimated with the new model. Furthermore, it
      uses simpler mathematical fitting routines and allows easier data acquisition,
      which may allow a more practicable clinical application of intermittent
      sonography. In conclusion, a more valid, detailed and accurate calculation of
      perfusion parameters, especially of tumors, can be derived in vivo with the new
      multivessel model of intermittent sonography.

PMID- 14597340
TI  - Doppler pressure field deduced from the Doppler velocity field in an observation
      plane in a fluid.
AB  - A new method is developed for a nondisturbing and quantitative measurement of the
      pressure at an arbitrary point in a flowing fluid in three-dimensional (3-D)
      space. In this method, after measuring the velocity field in the observation
      plane (scanning plane) using the pulsed Doppler technique, the velocity component
      orthogonal to the Doppler velocity is deduced, taking the law of conservation of
      mass (the equation of continuity) into consideration. Then, the pressure,
      "Doppler pressure," is calculated from the acceleration. It is expected that,
      when this method is applied to cardiology in clinical medicine, it will be very
      useful as a clinical diagnostic tool for the practical analysis and estimation of
      hemodynamics in the blood flow in the heart chambers, because the pressure field
      can be displayed as a 2-D contour.

PMID- 14597341
TI  - A robust and automatic method for evaluating accuracy in 3-D ultrasound-based
      navigation.
AB  - We present a robust and automatic method for evaluating the 3-D navigation
      accuracy in ultrasound (US) based image-guided systems. The method is based on a
      precisely built and accurately measured phantom with several wire crosses and an
      automatic 3-D template matching by correlation algorithm. We investigated the
      accuracy and robustness of the algorithm and also addressed optimization of
      algorithm parameters. Finally, we applied the method to an extensive data set
      from an in-house US-based navigation system. To evaluate the algorithm, eight
      skilled observers identified the same wire crosses manually and the average over
      all observers constitutes our reference data set. We found no significant
      differences between the automatic and the manual procedures; the average distance
      between the point sets for one particular volume (27 point pairs) was 0.27 +/-
      0.17 mm. Furthermore, the spread of the automatically determined points compared
      with the reference set was lower than the spread for any individual operator.
      This indicates that the automatic algorithm is more accurate than manual
      determination of the wire-cross locations, in addition to being faster and
      nonsubjective. In the application example, we used a set of 35 3-D US scans of
      the phantom under various acquisition configurations. The US frequency was 6.7
      MHz and the average target depth was 6 cm. The accuracy, represented by the mean
      distance between automatically-determined wire-cross locations and physically
      measured locations, was found to be 1.34 +/- 0.62 mm.

PMID- 14597342
TI  - Ultrasound-enhanced transgene expression in vascular cells is not dependent upon
      cavitation-induced free radicals.
AB  - Although acoustic cavitation is clearly important in ultrasound (US)-enhanced
      gene delivery (UEGD), the relative importance of mechanical and sonochemical
      (free radical) bioeffects remains unclear, as does the mechanism of gene delivery
      at the cellular level. Porcine vascular smooth muscle cells (VSMC) were
      transfected with luciferase or green fluorescent protein (GFP) plasmid +/- pulsed
      956 kHz US (2.0 mechanical index (MI), 128 W cm(-2) spatial peak pulse average
      intensity, ISPPA) for 60 s, in the presence or absence of 20 mM cysteamine or N
      acetyl-L-cysteine. Both compounds effectively scavenged free radical production
      following US, leaving unaffected the 50- to 100-fold enhancements in luciferase
      expression seen in US-treated VSMC. US exposure enhanced plasmid uptake (25 +/-
      4.6 vs. 3 +/- 1.9 cells/field, n=4, p<0.05), most likely directly into the
      cytoplasm, and increased both the total number (>sevenfold) and average
      fluorescence intensity (>sixfold) of GFP-transfected cells. UEGD is not dependent
      upon cavitation-induced free radical generation and has potential for use with a
      wide range of therapeutic transgenes.

PMID- 14597344
TI  - Functional and histological changes in rat femoral arteries by HIFU exposure.
AB  - This study was an investigation of arterial contractility in response to high
      intensity focused ultrasound (HIFU) and of histologic changes to the artery with
      various intensities of HIFU. We constructed a prototype HIFU transducer in
      combination with an imaging probe that provides color Doppler imaging and Doppler
      velocimetry. HIFU was applied through the skin to deep femoral arteries in left
      thighs of Sprague-Dawley rats; color images of the blood flow were used to aim
      the HIFU beam. Peak intensities used were 530, 1080, 2750 and 4300 W/cm2. The
      duration of each HIFU exposure was 5 s. HIFU was applied to five focal spots of
      each leg. These focal spots were aligned with a spacing of 1.0 mm so as to form a
      line across the artery. Blood flow occlusion was accomplished by HIFU at an
      intensity of 4300 W/cm2, but the flow continued with the lower intensities. Peak
      systolic velocities (PSVs) of blood flow as measured by Doppler velocimetry
      increased in the arteries to which HIFU had been applied at 1080 and 2750 W/cm2.
      The increase corresponded with HIFU intensity. Exposure to HIFU at 530 W/cm2 did
      not change the blood flow velocity. Histologic studies have demonstrated that
      exposure to HIFU at 2750 and 4300 W/cm2 leads to vacuolar degeneration and
      destruction of elastic fibers of the tunica media of the artery. Exposure at 1080
      W/cm2 led to increased PSV, but did not induce histologic changes in the vessel
      wall. In conclusion, the response of the artery to HIFU varied with intensity.
      Vascular contraction without tissue degeneration occurred at low intensity; with
      increasing intensity, the tissue degeneration detectable in histology reduced the
      vascular diameter and, finally, at high intensity, the blood flow was occluded.
      Although these phenomena appeared to be mainly due to thermal effects, mechanical
      effects might have some role, particularly on vascular contraction.

PMID- 14597343
TI  - Contrast agent bubble and erythrocyte behavior in a 1.5-MHz standing ultrasound
      wave.
AB  - Human erythrocytes and Optison contrast agent have been exposed to ultrasound,
      both alone and in combination, in a single-half-wavelength chamber driven at its
      resonance frequency (fo) of 1.5 MHz. Cell movements were recorded by video
      microscopy at speeds up to 500 frames/s. The hypothesis that cells near a
      standing wave pressure node might be stressed by the microbubble products of
      sonicated contrast agent was examined. In the absence of contrast agent, cells
      moved rapidly to form an aggregate in the standing wave pressure node plane.
      First subharmonic and second harmonic emissions were detected from cell-contrast
      agent suspensions immediately on exposure to a threshold peak pressure amplitude
      of 0.98 MPa. Emissions at 3fo/2 occurred at 1.47 MPa, whereas white noise and
      lower-order subharmonic emissions coincided with the appearance of visible
      bubbles at a threshold of approximately 1.96 MPa. Cells exposed together with
      contrast agent at a pressure of 0.98 MPa precessed very rapidly about the
      pressure node plane. This behavior was discussed in the context of a recent
      analysis predicting that, in contrast to the situation for lower-pressure
      amplitudes, subresonant size bubbles translate about pressure node plane if the
      driving pressure amplitude is sufficiently high. Many precessing erythrocytes
      were clearly spiculated and this morphology persisted after the cells had left
      the area of precession. Hemoglobin release was significant under conditions
      inducing precession with first subharmonic and first harmonic emissions. Protein
      release increased discontinuously near the pressure thresholds, where more
      complex categories of frequency emission were detected. The potential of this
      system, which induces erythrocyte morphology changes and some protein release at
      the first emission threshold, to provide some control on the membrane
      permeabilizing stress experienced by cells in a cavitation field is discussed.

PMID- 14597345
TI  - The relevance of cell size on ultrasound-induced hemolysis in mouse and human
      blood in vitro.
AB  - This paper describes a further test of the hypothesis that cell size is an
      important physical parameter in ultrasound (US)-induced hemolysis, that is, the
      larger the cell the greater the potential for sonolysis by a cavitational
      mechanism. Mouse (M) and human (Hu) erythrocytes in vitro were used; their mean
      corpuscular volumes were 49.0 and 89.5 fL, respectively. At a US exposure in
      vitro in the presence of Albunex that yielded an average of 36.8% hemolysis for M
      blood, the Hu blood yielded an average of 54.0% hemolysis. The data supported the
      hypothesis. This paper also briefly discusses the difficulty of extrapolating
      sonolytic in vitro results to those derived in vivo.

PMID- 14597346
TI  - Changes in biologic characteristics of breast cancer treated with high-intensity
      focused ultrasound.
AB  - Proliferation, invasion, immortalization and metastasis are the main malignant
      characteristics of cancer. Previous studies have shown that high-intensity
      focused ultrasound (US), or HIFU, can induce irreversible damage both to breast
      cancer cells and to tumor blood vessels. However, light microscopy alone may not
      always show this clearly. In this study, molecular biologic techniques were used
      to examine any changes in molecular markers associated with malignant behavior
      after exposure to HIFU. A total of 48 women with breast cancer were randomized to
      a control group (mastectomy) and a HIFU group (HIFU followed by mastectomy).
      Immunohistochemical staining, messenger RNA (mRNA) in situ hybridization and
      telomere-repeat amplification protocol-enzyme-linked immunosorbent assay (TRAP
      ELISA) techniques were used to detect tumor expression of proliferating cell
      nuclear antigen (PCNA), cell adhesion molecule CD44v6, matrix metalloproteinase-9
      (MMP-9), erbB2 mRNA, and to measure telomerase activity in both groups. The
      results demonstrated that there were significant alterations in expression of
      PCNA, CD44v6, MMP-9, erbB2 mRNA, and a dramatic decrease in telomerase activity
      in the HIFU group. It is concluded that malignant tumor characteristics are
      arrested by HIFU, and that biologic factors are potential markers for assessing
      HIFU efficacy.

PMID- 14597347
TI  - Transfer function analysis of ultrasonic time-intensity measurements.
AB  - Time-intensity measurements of ultrasonic-contrast microbubbles based on the
      dilution theory have been used to assist blood flow estimation. The compartment
      model has been employed to describe the dilution process. Under the linear and
      time-invariant assumption, the time-intensity curve measured at the output of a
      compartment (i.e., blood mixing chamber) is the convolution of the input time
      intensity curve with the compartment's transfer function. Thus, transfer function
      analysis is possible using deconvolution when the temporal variations in both the
      input and the output intensities are available. Note that the linear and time
      invariant assumption requires a constant flow rate because, with flow pulsation,
      the flow rate changes with time and the mixing process becomes time varying.
      Thus, the purpose of this paper was to study the effects of flow pulsation on
      time-intensity measurements. In addition, a deconvolution technique based on a
      recursive least squares approach is used for transfer function analysis. Both
      simulations and experiments were performed; the results from which indicate that
      the pulsation generally does not affect the validity of time-intensity-based flow
      estimation. The proposed deconvolution technique is also effective for both
      constant and pulsatile flows; thus, permitting transfer function analysis in
      various flow conditions. One potential application of this transfer function
      analysis is to remove the effects of a noninstantaneous input function. The
      results from this paper lead to future work in brain-perfusion estimation based
      on extracranial time-intensity measurements.

PMID- 14597348
TI  - Therapeutic ultrasound improves strength of achilles tendon repair in rats.
AB  - The purpose of this study was to evaluate the effects of therapeutic ultrasound
      on structural properties and functional performance of Achilles tendon healing.
      Thirty Sprague-Dawley rats with surgical hemitransected Achilles tendon were
      studied. Ten were treated daily with 1 MHz continuous ultrasound at 1.0 W/cm2 for
      4 min, 11 at 2.0 W/cm2 for 4 min and nine served as control without treatment.
      Achilles functional index (AFI) was recorded preoperatively and on postoperative
      days 3, 10 and 30. On day 30, the rats were sacrificed and Achilles tendons were
      tested for load-relaxation, stiffness and ultimate tensile strength (UTS).
      Results showed that UTS of both low-dose (p=0.023) and high-dose (p=0.002) groups
      was significantly greater than in controls. No significant differences in AFI
      (p=0.179), load-relaxation (p=0.205) and stiffness (p=0.842) were found among
      groups. These findings suggested that both low- and high-dose therapeutic
      ultrasound accelerate the healing process of ruptured tendon.

PMID- 14597349
TI  - Measurement of ultrasonic power using an acoustically absorbing well.
AB  - This paper describes a quick and cost-effective method for constructing a
      radiation force balance for measuring ultrasonic output power. It utilises a
      target manufactured from a high-quality acoustical absorber material. The target
      geometry is in the form of a cup or well that is water-filled and placed directly
      on the pan of a top-loading chemical balance, thus overcoming the need for the
      traditional gantry arrangement found in the majority of commercially available
      balances. The face of the transducer is placed directly in the water contained
      within the well. This simplification reduces time spent in setting up a balance
      for measurement, and targets can be manufactured to any required geometry and
      used on any suitable top-loading balance to measure output power. Within this
      study, the performance of the absorbing well method was evaluated over the
      frequency range of 1 MHz to 5 MHz, for acoustic power levels up to 1 W. Power
      measurements on three transducers were compared with measurements made on the
      National Physical Laboratory (NPL) primary standard radiation force balance and
      good agreement is demonstrated between the two systems. At a power of 50 mW,
      using a chemical balance of resolution 0.1 mg, typical type A (random)
      uncertainties were +/- 2.0% when expressed at the 95% confidence level.

PMID- 14597351
TI  - Incorporating an improved dose-calculation algorithm in conformal radiotherapy of
      lung cancer: re-evaluation of dose in normal lung tissue.
AB  - BACKGROUND AND PURPOSE: The low density of lung tissue causes a reduced
      attenuation of photons and an increased range of secondary electrons, which is
      inaccurately predicted by the algorithms incorporated in some commonly available
      treatment planning systems (TPSs). This study evaluates the differences in dose
      in normal lung tissue computed using a simple and a more correct algorithm. We
      also studied the consequences of these differences on the dose-effect relations
      for radiation-induced lung injury. MATERIALS AND METHODS: The treatment plans of
      68 lung cancer patients initially produced in a TPS using a calculation model
      that incorporates the equivalent-path length (EPL) inhomogeneity-correction
      algorithm, were recalculated in a TPS with the convolution-superposition (CS)
      algorithm. The higher accuracy of the CS algorithm is well-established. Dose
      distributions in lung were compared using isodoses, dose-volume histograms
      (DVHs), the mean lung dose (MLD) and the percentage of lung receiving >20 Gy
      (V20). Published dose-effect relations for local perfusion changes and radiation
      pneumonitis were re-evaluated. RESULTS: Evaluation of isodoses showed a
      consistent overestimation of the dose at the lung/tumor boundary by the EPL
      algorithm of about 10%. This overprediction of dose was also reflected in a
      consistent shift of the EPL DVHs for the lungs towards higher doses. The MLD, as
      determined by the EPL and CS algorithm, differed on average by 17+/-4.5% (+/
      1SD). For V20, the average difference was 12+/-5.7% (+/-1SD). For both
      parameters, a strong correlation was found between the EPL and CS algorithms
      yielding a straightforward conversion procedure. Re-evaluation of the dose-effect
      relations showed that lung complications occur at a 12-14% lower dose. The values
      of the TD(50) parameter for local perfusion reduction and radiation pneumonitis
      changed from 60.5 and 34.1 Gy to 51.1 and 29.2 Gy, respectively. CONCLUSIONS: A
      simple tissue inhomogeneity-correction algorithm like the EPL overestimates the
      dose to normal lung tissue. Dosimetric parameters for lung injury (e.g. MLD, V20)
      computed using both algorithms are strongly correlated making an easy conversion
      feasible. Dose-effect relations should be refitted when more accurate dose data
      is available.

PMID- 14597352
TI  - Loco-regional differences in pulmonary function and density after partial rat
      lung irradiation.
AB  - PURPOSE: The purpose of this study was to explore regional differences in
      radiosensitivity of rat lung using lung function and computed tomography (CT)
      density as endpoints. METHODS: At first, CT scans were used to determine rat lung
      volumes. The data obtained enabled the design of accurate collimators to
      irradiate 50% of the total lung volume for the apex, base, left, right,
      mediastinal and lateral part of the lung. Male Wistar rats were irradiated with a
      single dose of 18 Gy of orthovoltage X-rays. Further rat thorax CT scans were
      made before and 4, 16, 26, and 52 weeks after irradiation to measure in vivo lung
      density changes indicative of lung damage. To evaluate overall lung function,
      breathing frequencies were measured biweekly starting 1 week before irradiation.
      RESULTS: Qualitative analysis of the CT scans showed clear density changes for
      all irradiated lung volumes, with the most prominent changes present in the
      mediastinal and left group at 26 weeks after radiation. Quantitative analysis
      using average density changes of whole lungs did not adequately describe the
      differences in radiation response between the treated groups. However, analysis
      of the density changes of the irradiated and non-irradiated regions of interest
      (ROI) more closely matched with the qualitative observations. Breathing
      frequencies (BF) were only increased after 50% left lung irradiation, indicating
      that the hypersensitivity of the mediastinal part as assessed by CT analysis,
      does not result in functional changes. CONCLUSIONS: For both BF and CT (best
      described by ROI analysis), differences in regional lung radiosensitivity were
      observed. The presentation of lung damage either as function loss or density
      changes do not necessarily coincide, meaning that for each endpoint the regional
      sensitivity may be different.

PMID- 14597353
TI  - Simple radiographic parameter predicts fracturing in metastatic femoral bone
      lesions: results from a randomised trial.
AB  - BACKGROUND AND PURPOSE: In the randomised Dutch Bone Metastasis Study on the
      palliative effect of a single fraction (SF) of 8 Gy versus six fractions of 4 Gy
      on painful bone metastases, 14 fractures occurred in 102 patients with femoral
      metastases. Purpose of the present study was to identify lesional risk factors
      for fracturing and to evaluate the influence of the treatment schedule. MATERIAL
      AND METHODS: Pretreatment radiographs of femoral metastases were collected. Three
      observers separately measured the lesions and scored radiographic
      characteristics. RESULTS: Ten fractures occurred after median 7 weeks in 44 SF
      patients (23%) and four after median 20 weeks in 58 multiple fraction patients
      (7%) (UV, P=0.02). In 110 femoral metastases, an axial cortical involvement >30
      mm significantly predicted fracturing (MV, P=0.02). Twelve out of 14 fractured
      lesions and 40 out of 96 non-fractured metastases had an axial cortical
      involvement >30 mm (negative predictive value, 97%). When correcting for the
      axial cortical involvement, the treatment schedule was not predictive anymore
      (MV, P=0.07). CONCLUSIONS: Fracturing of the femur mostly depended on the amount
      of axial cortical involvement of the metastasis. We recommend to treat femoral
      metastases with an axial cortical involvement < or =30 mm with an SF of 8 Gy for
      relief of pain. If the axial cortical involvement is >30 mm, prophylactic surgery
      should be performed to minimize the risk of pathological fracturing or, if the
      patient's condition is limited, irradiation to a higher total dose.

PMID- 14597354
TI  - The potential palliative role and possible immune modulatory effects of low-dose
      total body irradiation in relapsed or chemo-resistant non-Hodgkin's lymphoma.
AB  - In a group of 35 patients with relapsed and/or chemo-resistant non-Hodgkin's
      lymphoma (NHL), low-dose total body irradiation (LTBI) (+involved-field
      radiotherapy to bulky sites) achieved a complete remission rate of 29%, 2-years
      progression-free survival of 32% and a median progression-free survival of 12
      months. The 2-year survival was 42% and the median survival was 17 months. Immuno
      staining and flow cytometry of peripheral blood in 14 patients showed that LTBI
      leads to a significant increase in the percentage of CD4+ cells with a consequent
      significant increase in the CD4+/CD8+ ratio. High lymphocytic percent and a high
      percentage of CD4+ cells before LTBI were significantly correlated with longer
      response duration and overall survival. These data may suggest that the
      palliative potential of LTBI should be investigated as an alternative to
      chemotherapy in NHL patients. The pre-treatment percentage of lymphocytes and
      CD4+ cells may be used as predictors for response to LTBI.

PMID- 14597355
TI  - Radiotherapy for head and neck cancer in elderly patients.
AB  - BACKGROUND AND PURPOSE: Elderly patients with head and neck cancer may not be
      treated aggressively with radiotherapy, due to concerns regarding tolerance of
      treatment and toxicity. A retrospective study was undertaken of patients aged 80
      years and over, treated by definitive radiotherapy for head and neck cancer.
      MATERIAL AND METHODS: 98 patients aged 80-92 received radiotherapy for carcinoma
      of the head and neck between 1991 and 1995. All patients received beam directed
      radiotherapy with radical intent using an immobilisation shell. RESULTS: Cancer
      specific survival was 59% and overall local control was 70% at 5 years. Both were
      significantly affected by T stage and site of disease. Cancer specific survival
      was comparable to that of patients aged below 80 years. Seven patients died
      within 6 months of the treatment. Three patients developed severe late toxicity.
      Metastatic disease occurred in eight patients. CONCLUSIONS: Radiotherapy is a
      beneficial and well tolerated treatment in elderly patients with carcinoma of the
      head and neck.

PMID- 14597356
TI  - A systematic study of techniques for elective cervical nodal irradiation with
      anterior or opposed anterior and posterior beams.
AB  - PURPOSE: To assess target coverage and dose homogeneity using conventional
      radiotherapy (RT) and intensity-modulated RT (IMRT) with anterior and posterior
      beams for elective irradiation of the cervical lymph nodes in patients with head
      and neck cancer. MATERIALS AND METHODS: A planning study was performed in six
      patients who had undergone radical RT for head and neck cancer. RT plans to
      irradiate the cervical lymph nodes using a single anterior field, or opposed
      anterior and posterior fields, with 6 or 10 MV photons were compared. Plans using
      IMRT for missing-tissue compensation were also studied. An algorithm was
      developed to guide clinicians to the most appropriate treatment technique
      depending on the nodal groups to be irradiated. RESULTS: With 6 MV single field
      (SF) irradiation significant under-dose (minimum dose <70% of prescription dose)
      was seen in nodal groups II and V, due to their posterior position. With SF 10 MV
      the mean dose to level II was higher (p<0.001) and dose homogeneity to levels Ib
      and II was improved. Using opposed fields (OF), minimum doses to the nodes in
      levels II and V were improved. OF using 10 MV showed significant advantage over 6
      MV with reduction of maximum doses to levels II, III and V. SF 10 MV IMRT
      improved maximum doses to levels Ib and II compared to SF 6 MV IMRT. OF IMRT gave
      the best dose distributions with optimal mean dose and dose homogeneity. Beam
      energy made no difference with OF IMRT. CONCLUSIONS: The optimal technique for
      elective cervical node irradiation depends on the lymph node levels within the
      PTV. If irradiation of the level II or V nodes is required, then the OF IMRT
      technique with either 6 or 10 MV gives the best dose distributions. In the
      absence of IMRT, then OF conventional techniques are best. If the aim is to
      irradiate levels III and IV or level IV only, then 6 MV SF non-IMRT is the
      simplest technique.

PMID- 14597357
TI  - A prospective study of pre-treatment cell kinetics and clinical outcome in
      nasopharyngeal carcinoma.
AB  - BACKGROUND AND PURPOSE: To study pre-treatment cell kinetics and their clinical
      correlations in nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: Ninety
      newly diagnosed NPC patients were studied using in vivo Bromodeoxyuridine (BrdU)
      labeling and flow cytometric analysis. Immunohistochemical staining for BrdU and
      Ki 67 was also performed. RESULTS: The median S-phase duration (Ts) was 6.2 h
      (range 3.5-18.7 h), median flow cytometric labeling index (FCM-LI) was 7.4% (1.3
      37.6%), and median potential doubling time (Tpot) was 3.6 days (0.5-19.9 days).
      The median histologic labeling index (H-LI) was 12.4% (1.2-43.3%), and median
      histologic Tpot (H-Tpot) was 2.1 days (0.5-33.3 days). FCM-LI and H-LI were both
      positively correlated with Ki67 whereas Tpot and H-Tpot were both negatively
      correlated with Ki67 and N-stage. In univariate analysis, Tpot and H-Tpot showed
      a trend for progression free survival. Tpot was significantly associated with
      local relapse free survival, but lost its significance in multivariate analysis.
      N-stage was the only significant prognostic factor for all radiotherapy outcomes
      in both univariate and multivariate analyses. CONCLUSIONS: Tpot was the only pre
      treatment cell kinetic parameter for which some evidence was found for an
      association with survival in NPC patients. Future studies should aim to combine
      cell kinetic parameters together with other biological markers and clinical
      parameters to provide more useful prognostic information to guide individual
      patient's therapy.

PMID- 14597358
TI  - Contemporary management of prostate cancer: a practice survey of Ontario
      genitourinary radiation oncologists.
AB  - OBJECTIVE: To survey radiation oncology practice in the utilization of hormonal
      and radiation therapy in the primary, adjuvant and salvage treatment of localized
      prostate cancer. MATERIALS AND METHODS: Genitourinary radiation oncologists
      practicing in Ontario were invited to participate in a practice survey examining
      staging, hormonal and radiation management, and radiation technique for a variety
      of common clinical scenarios. Background demographic information was collected on
      all respondents. The survey consisted of three cases relating to the
      hormonal/radiation management of low-, intermediate-, and high-risk prostate
      cancer as well as two adjuvant and one salvage post-prostatectomy scenarios. The
      survey response rate was 70% (26/37). RESULTS: Clinicians were more likely to
      utilize laboratory and imaging studies for staging as the risk categorization
      increased. Low-risk disease was managed with radiation alone in 26/26 (70 Gy in
      65%, 74-79.8 Gy in 35%). Intermediate-risk disease was managed with radiation (70
      Gy in 46%, 74-79.8 Gy in 54%) with neoadjuvant hormones in 58%. All respondents
      managed high-risk disease with adjuvant hormones in addition to radiation therapy
      (70-71 Gy in 85%, and 76 Gy in 15%). In the pT3a, margin negative (PSA
      undetectable) scenario, most individuals would not recommend adjuvant radiation
      (73%). If margins were positive, 30% would still not recommend adjuvant
      radiation. In the salvage scenario (slowly rising PSA 4 years post-prostatectomy
      for pT2a close margin disease), all respondents would manage with radiation
      therapy. Hormones were not routinely recommended in the initial management of the
      adjuvant and salvage scenarios. Radiation doses utilized for both adjuvant and
      salvage treatment ranged from 60-70 Gy (median 66 Gy). CONCLUSIONS: General
      agreement exists for the management of low- and high-risk disease and in the post
      prostatectomy salvage setting. Use of dose-escalation and neoadjuvant hormones in
      the intermediate-risk setting and use of post-prostatectomy adjuvant radiation in
      the pT3a scenarios varied among radiation oncologists. Current clinical practice
      in localized prostate cancer reflects the evolving information in the published
      medical literature.

PMID- 14597359
TI  - External beam radiation therapy to prevent anastomotic intimal hyperplasia in
      prosthetic arteriovenous fistulas: results of a randomized trial.
AB  - External beam irradiation has a documented effect on intimal hyperplasia
      reduction. However, it did not result in less reinterventions or stenoses after
      radiation treatment of the venous anastomosis in polytetrafluoroethylene dialysis
      access.

PMID- 14597360
TI  - Development and clinical application of a fast superposition algorithm in
      radiation therapy.
AB  - BACKGROUND AND PURPOSE: Dose calculation algorithms play a central role for the
      optimization and verification of treatment plans in radiation therapy. Complex
      treatment techniques like intensity modulated radiotherapy (IMRT) require
      accurate and fast dose algorithms especially for clinical cases which involve
      severe tissue inhomogeneities. For these cases the standard dose engine in
      current treatment planning systems--the convolution of photon pencil beams-
      usually fails to predict the dose with the required accuracy. The role of more
      accurate but time consuming dose calculations like superposition algorithms or
      Monte Carlo simulations in clinical practice is under investigation at several
      therapy centers. PATIENTS AND METHODS: The paper presents the design,
      implementation and the first application of a superposition algorithm in a
      clinical setting at the German Cancer Research Center (DKFZ). It first describes
      in detail how the superposition algorithm is adapted to the dose delivery system
      at DKFZ in terms of standard dosimetric data. Then details of the implementation
      of the algorithm are given with a focus on various methods for the reduction of
      dose computation times. Next, the algorithm is evaluated in various experiments
      with dosimetric phantoms. These studies are employed for the development of time
      efficient sampling strategies of the elemental dose kernels. Finally, the
      algorithm is applied to dose calculations of clinical cases with tumors adjacent
      to lung tissue. RESULTS: Severe differences in dose coverage of the tumors and
      dose burden of the surrounding tissues in comparison to standard pencil beam
      calculations are observed. A standard 4-7 beam plan in a convenient dose grid
      (approximately 3 mm in each direction) is calculated in about 30 min on a Pentium
      4 (1.9 GHz) applying the superposition algorithm described here.

PMID- 14597361
TI  - The IAEA/WHO TLD postal dose quality audits for radiotherapy: a perspective of
      dosimetry practices at hospitals in developing countries.
AB  - BACKGROUND AND PURPOSE: The IAEA/WHO TLD postal programme for external audits of
      the calibration of high-energy photon beams used in radiotherapy has been in
      operation since 1969. This work presents a survey of the 1317 TLD audits carried
      out during 1998-2001. The TLD results are discussed from the perspective of the
      dosimetry practices in hospitals in developing countries, based on the
      information provided by the participants in their TLD data sheets. MATERIALS AND
      METHODS: A detailed analysis of the TLD data sheets is systematically performed
      at the IAEA. It helps to trace the source of any discrepancy between the TLD
      measured dose and the user stated dose, and also provides information on
      equipment, dosimetry procedures and the use of codes of practice in the countries
      participating in the IAEA/WHO TLD audits. RESULT: The TLD results are within the
      5% acceptance limit for 84% of the participants. The results for accelerator
      beams are typically better than for Co-60 units. Approximately 75% of
      participants reported dosimetry data, including details on their procedure for
      dose determination from ionisation chamber measurements. For the remaining 25% of
      hospitals, who did not submit these data, the results are poorer than the global
      TLD results. Most hospitals have Farmer type ionisation chambers calibrated in
      terms of air kerma by a standards laboratory. Less than 10% of the hospitals use
      new codes of practice based on standards of absorbed dose to water. CONCLUSION:
      Despite the differences in dosimetry equipment, traceability to different
      standards laboratories and uncertainties arising from the use of various
      dosimetry codes of practice, the determination of absorbed dose to water for
      photon beams typically agrees within 2% among hospitals. Correct implementation
      of any of the dosimetry protocols should ensure that significant errors in
      dosimetry are avoided.

PMID- 14597362
TI  - Dose-volume histogram evaluation of prone and supine patient position in external
      beam radiotherapy for cervical and endometrial cancer.
AB  - BACKGROUND AND PURPOSE: To evaluate the influence of patient positioning on dose
      volume histograms of organs at risk in external beam radiotherapy for cervical
      and endometrial cancer. MATERIALS AND METHODS: In 20 patients scheduled for
      definitive (7) or postoperative (13) external beam radiotherapy of the pelvis
      treatment planning CT scans were performed in supine and prone (belly board)
      positions. After volume definition of target and organs at risk treatment plans
      were calculated applying the four-field box technique. The dose-volume histograms
      of organs at risk were compared. RESULTS: Radiotherapy in prone position causes a
      reduction of the bladder portion (mean 15%, p<0.001) and an increase of the
      rectum portion (mean 11%, p<0.001) within the 90% isodose. A reduction of the
      bowel portion could only be observed in postoperatively treated patients (mean
      13%, p<0.001). In definitive radiotherapy the target volume increases in supine
      position (mean 7%, p=0.02) due to an anterior tumour/uterus movement, so that
      bowel portions within the 90% isodose are similar. The bladder filling correlates
      with a reduction of bladder and bowel (postoperatively treated patients) dose.
      CONCLUSIONS: External beam radiotherapy of the pelvis should be performed in
      prone position in postoperative patients because of best bowel protection.
      Considering the additional HDR brachytherapy rectum protection takes the highest
      priority in definitive treatment-the requirements are best met in supine
      position. An adequate bladder filling is important to reduce the irradiated
      bladder and bowel volumes.

PMID- 14597363
TI  - Phantom study of radiation doses outside the target volume brachytherapy versus
      external radiotherapy of early breast cancer.
AB  - BACKGROUND AND PURPOSE: Brachytherapy is sometimes suggested as an adjuvant
      treatment after surgery of some tumours. When introducing this, it would be
      useful to have an estimate of the dose distribution to different body sites, both
      near and distant to target, comparing conventional external irradiation to
      brachytherapy. The aim of the present study was to determine radiation doses with
      both methods at different body sites, near and distant to target, in an
      experimental situation on an operated left sided breast cancer on a female
      Alderson phantom. METHODS: Five external beam treatments with isocentric
      tangential fields were given by a linear accelerator. A specified dose of 1.0 Gy
      was given to the whole left sided breast volume. Five interstitial brachytherapy
      treatments were given to the upper, lateral quadrant of the left breast by a two
      plane, 10 needles implant. A dose of 1.0 Gy specified according to the Paris
      system was administered by a pulsed dose rate afterloading machine. Absorbed dose
      in different fixed dose points were measured by thermoluminescence dosimeters.
      RESULTS: Both methods yielded an absorbed dose of the same size to the bone
      marrow and internal organs distant to target, 1.0-1.4% of the prescribed dose.
      There was a trend of lower doses to the lower half of the trunk and higher doses
      to the upper half of the trunk, respectively, by brachytherapy. A 90% reduction
      of absorbed dose with brachytherapy compared to external irradiation was found in
      the near-target region within 5 cm from target boundary where parts of the left
      lung and the heart are situated. If an adjuvant dose of 50 Gy is given with the
      external radiotherapy and brachytherapy, the absorbed dose in a part of the
      myocardium could be reduced from 31.8 to 2.1 Gy. CONCLUSIONS: Near target,
      brachytherapy yielded a considerably lower absorbed dose which is of special
      importance when considering radiation effects on the myocard and lungs. We could
      not demonstrate any difference of importance, in absorbed dose to dose points
      distant to target.

PMID- 14597364
TI  - Lip cancer treatment with high dose rate brachytherapy.
AB  - We present 39 patients with lip carcinoma treated with HDR, (needles) with 5-5.5
      Gy per 8-10 fractions b.i.d. (total dose 40.5-45 Gy). Three-year cause-specific
      survival and local control are 91 and 88% (95% T1-2, 74% T4, p<0.05). Acute and
      chronic reactions are like LDR cases. We think that HDR results are equivalent to
      LDR.

PMID- 14597365
TI  - Outpatient treatment suite: a safe and cost-effective venue to perform
      myringotomy and tubes placement in children.
AB  - CONTEXT: Otitis media (OM) is the most common reason that a child undergoes a
      general anesthetic, with the total costs of treating this disease exceeding five
      billion dollars annually. Concerns regarding the development of antibiotic
      resistant organisms in response to medical treatment for OM have fueled the
      demand for surgical intervention. However, reimbursements are decreasing. Non
      traditional settings for children requiring bilateral myringotomy and tube (BMT)
      placement for ear disease have the potential to offer the same degree of patient
      safety and improved efficiency but at lower cost. OBJECTIVE: To develop a non
      traditional setting for BMT surgery that is safe, cost effective, and well
      received by patients, families and staff. DESIGN: Prospective design of an
      outpatient treatment suite (OTS) for BMT placement; prospective evaluation of
      safety and family satisfaction; analysis of costs. SETTING: A 778 bed US urban
      area level one trauma center and teaching hospital, with a 2160 ft(2) electro
      convulsive therapy suite that was underutilized and non-revenue generating on
      Tuesdays and Thursdays. PARTICIPANTS: A design task force of health care
      providers, administrators and operations personnel; 794 healthy children between
      the ages of 6 months to 16 years requiring BMT surgery; 100 families of patients.
      MAIN OUTCOME MEASURES: Financial comparison was made between the traditional
      operating room (OR) setting, the outpatient surgery center (SC) and the OTS
      comparing overhead and indirect costs to run each site. A prospective survey was
      conducted of 100 consecutive patients undergoing surgery between November 2000
      and June 2001. The survey was conducted at the 2 weeks postoperative check and
      was composed of 18 questions divided into five sections, with a 5-point rating
      scheme, with one being very poor, and five being very good. RESULTS: Designing a
      new treatment venue was successful because of teamwork and a willingness to think
      creatively. The OTS was found to be far more cost-effective than both the main OR
      and SC for BMTs. The contribution to margin for the SC was US$ 280 per case and
      for the main OR was US$ 2130 per case. By operating on 794 patients in OTS, the
      hospital was able to generate additional contribution to margin of US$ 197,100
      when compared to the cost of performing these cases in the SC and US$ 1,499,500
      when compared to performing all cases in the main OR. No adverse consequences
      were noted. Patient/Family satisfaction was also rated very high, with an overall
      rating of 4.85 and markedly reduced time in hospital. CONCLUSION: Operating rooms
      (ORs) today are busier than in years past, but revenues barely meet or in some
      cases fall below expenses due to insurers' decreased reimbursement. This
      innovative approach to BMT placement has been shown to be safe and results in
      excellent family satisfaction, with a substantial contribution to margin. As over
      one million BMT cases are performed annually in the US, adoption of this approach
      nationally has the potential to markedly reduce the treatment costs of this
      common disease.

PMID- 14597366
TI  - Anthropometric growth study of normal human auricle.
AB  - OBJECTIVE: The aim of this study was to reveal the anthropometric growth of
      auricula from birth to the age of 18 years and to bring out the dynamics of ear
      growth. MATERIAL AND METHODS: A total of 1552 children in 50 groups were
      evaluated. Six surface measurements were performed directly on the right auricle
      of the subjects: the length from the superaurale to subaurale, the width from the
      tragus to helix, the width from the tragus to antihelix, the conchal depth, the
      height from the helix to mastoid at superauraler level, and the height from the
      helix to mastoid at tragal level. The frequency of prominent ear deformity and
      the degree of attachment of the lobule were also noted. RESULTS: Vertical
      auricular growth was complete in girls at the age of 11 and in boys at the age of
      12, whereas the auricular width from the tragus to helix, the height from the
      helix to mastoid at superauraler level and the height from the helix to mastoid
      at tragal level were found almost complete at the age of 6. The auricular width
      from the tragus to antihelix attained its full size at 6 months for girls and 12
      months for boys. The conchal depth was found almost complete at the age of 5 in
      both sexes. The incidence of prominent ear deformity and attached lobule was 9.8
      and 26.5%, respectively. CONCLUSIONS: Different ear growth pattern and maturation
      size from previously published reports are obtained in different populations.
      There is still need for future studies comparing populations with different
      social and ethnic background to interpret common knowledge about the size of the
      ear. This study gives dimensional information and the growth pattern of the
      auricle, and therefore may reveal important implications for the adequate timing
      of the surgical treatment of auricular deformity.

PMID- 14597367
TI  - Otitis media with effusion and histopathologic properties of adenoid tissue.
AB  - OBJECTIVE: Adenoidectomy is being generally used for the treatment of otitis
      media with effusion (OME). The purpose of current study was to determine
      objectively the significance of the histopathology of adenoid tissue on the
      development of otitis media with effusion. METHODS: The records of all the
      patients operated on with the diagnosis of adenoid enlargement with or without
      OME were reviewed and pathologic specimen were re-evaluated regarding
      histopathological properties by one pathologist unfamiliar with the diagnosis.
      Sixty-one patients with adenoid hyperplasia were enrolled in the study group, 38
      males and 23 females. Age ranged between 3 and 13 years (mean age was 7.03+/-3.26
      years). All the patients of study group were those operated on due to the adenoid
      hyperplasia and uni- or bilateral OME. Control group was composed of 39 male and
      26 female patients (age range was between 3 and 13 years, and mean age was 7.06+/
      3.04 years) with solely adenoid hyperplasia. RESULTS: The squamous metaplasia was
      present in 47 (77%) and 14 (22%) patients of study and control groups,
      respectively. The fibrosis of connective tissue interspersed follicles of adenoid
      was present in 29 (48%) and 6 (9%) patients of study and control groups,
      respectively. The statistical analysis revealed a significant prevalence of
      squamous metaplasia (P<0.001) and fibrosis of connective tissue interspersed
      follicles of adenoid (P<0.001) for a surgical indication of adenoid hyperplasia
      with OME than for without OME. The prevalence of other parameters was not
      significantly different between two groups. CONCLUSIONS: Adenoid tissue not only
      exerts an obstructive influence on the eustachian tube lumen when enlarged, but
      also impedes (hinders) mucociliary drainage of the middle ear by the way of non
      ciliated metaplastic epithelium and fibrosis of connective tissue.

PMID- 14597368
TI  - Expression of mast cell tryptase in pediatric otitis media with effusion.
AB  - OBJECTIVE: To evaluate the possible relationship between allergy and otitis media
      with effusion (OME), we investigated the presence and level of tryptase, which
      reflect mast cell activity. MATERIALS AND METHODS: Twenty-five children with
      intractable OME were studied. Thirteen patients were confirmed allergy positive
      by multiallergosorbent test. Twelve patients were allergy negative. Evidence for
      mast cell tryptase presence and degree of activation in the middle ear effusion
      (MEE) were measured by using Western blotting and radioimmunoassay (RIA).
      RESULTS: The typical single band of 32 kDa tryptase was found in the MEE. And it
      was more strongly expressed in the MEE with allergy positive than negative. RIA
      demonstrated that mean tryptase level was significantly higher in the MEE with
      allergy positive than negative. CONCLUSION: These results suggest that allergy
      may be one of the contributing factors in the persistence of intractable OME.

PMID- 14597369
TI  - Aplasia of zygomatic arch and dislocation of temporomandibular joint capsule in
      Treacher-Collins syndrome: three-dimensional reconstruction of computed
      tomographic scans.
AB  - Seven patients with Treacher-Collins syndrome were studied. All of patients were
      children or teenagers. Helical CT scanner (Toshiba) was used to reconstruct
      zygomatic arch and temporomandibular joint capsule on lateral aspect of temporal
      bone in five patients of microtia and atresia of both ears and two patients of
      narrow ear canals of both ears without microtia.Three-dimensional reconstructions
      of computed tomography on lateral aspect of temporal bone demonstrated various
      congenital abnormality including aplasia of zygomatic arch in seven patients and
      dislocation of temporomandibular joint capsule in seven patients.

PMID- 14597370
TI  - A clinical test of dynamic visual acuity for children.
AB  - OBJECTIVE: Children with sensorineural hearing impairment (SNHI) and concomitant
      vestibular hypofunction demonstrate deficits in gaze stability that may affect
      reading. The objective of this study was to develop a reliable, valid clinical
      test of dynamic visual acuity (DVA) for children. METHODS: Seventy-six typically
      developing children, 26 adults and 11 children with sensorineural hearing
      impairment participated. Visual acuity was tested under three conditions: (1)
      head stable (static acuity), (2) head tipped forward 30 degrees and passively
      rotated 30 degrees in the yaw plane at 2 Hz (horizontal dynamic acuity) and (3)
      head passively moved in the pitch plane 30 degrees at 2 Hz (vertical dynamic
      acuity, vDVA). The difference, in number of chart lines, between static dynamic
      acuity was calculated (dynamic acuity score). Based on normative data collected,
      results were scored as: (1) pass < or =2S.D. from the normative mean and (2) fail
      > or =2S.D. from normative mean. Children were grouped by age to enable
      examination of the effect of age on scores. RESULTS: We found excellent test
      retest and inter-tester reliability (ICC(2,2)=0.94 and ICC(3,2)=0.84) for the
      horizontal dynamic acuity (hDVA) test. Sensitivity, specificity, positive and
      negative predictive values were 100% to identify children with bilateral
      vestibular hypofunction (BVH). Although a statistical difference was found, the
      difference was not clinically significant (all achieved DVA scores <2 lines). The
      vertical dynamic acuity test was not tolerated by most children, precluding its
      usefulness. CONCLUSIONS: The clinical test of horizontal dynamic acuity is a
      reliable test for children as young as 3 years. It is simple and inexpensive, and
      will enable identification of those for whom more extensive testing is warranted.

PMID- 14597371
TI  - The prevalence of nasal septal deviation in children from Kahramanmaras, Turkey.
AB  - OBJECTIVE: The aim of this study was to determine the prevalence of nasal septal
      deformities among Turkish school children, in the city of Kahramanmaras in
      Turkey. METHODS: Study included 1234 Caucasian children attending pre-school,
      primary and secondary schools. All of the children underwent nasal examinations.
      Pathological septal deformities were grouped into seven types by using Mladina's
      classification. The differences among the types of nasal septal deformity (NSD)
      and between sexes were tested by chi(2)-test for independent samples. RESULTS:
      The overall prevalence of NSD has been found to be 34.9%. For the age groups, the
      prevalence of NSD was 16.5% in pre-school children, 38.7% in primary school
      children and 39.9% in secondary school children. Type 1 NSD was the most commonly
      seen deformity among all age groups. Anterior deformities (types 1 and 2) were
      the most commonly encountered types in pre-school children, but the occurrences
      of the posterior deformities (types 3-5) was relatively increased as the age
      increased. Neither the distribution of NSD types nor the overall prevalence
      showed any statistically significant difference between both sexes. CONCLUSION:
      We found that the prevalence of NSD and the occurrence of the posterior
      deformities was relatively increased as the age increased. Our study may reflect
      the prevalence of septal deviation in Turkish children in Kahramanmaras, an
      eastern Mediterranean city of Turkey. However, further studies throughout the
      country are needed.

PMID- 14597372
TI  - The epidemiology of acute bullous myringitis and its relationship to recurrent
      acute otitis media in children less than 2 years of age.
AB  - OBJECTIVE: To evaluate the epidemiological characteristics of acute bullous
      myringitis (BM), i.e. inflammation of the tympanic membrane with blister(s) in
      children <2 years and study the relationship between bullous myringitis and
      recurrent acute otitis media. METHODS: 2028 children aged 7-24 months in a
      prospective longitudinal cohort study in the Finnish Otitis Media vaccine trial.
      The main outcome measures were the incidence of bullous myringitis and the
      incidence of acute otitis media (AOM) before and after the event of bullous
      myringitis. RESULTS: 82 children had a total of 86 events of acute bullous
      myringitis. The incidence of bullous myringitis was 5.7 per 100 person years (95%
      CI, 4.6-7.1 per 100 person years). The number of events with bullous myringitis
      was 4.6% of the number of all AOM events diagnosed during the follow-up.
      Recurrent AOM (> or =6 AOM events) occurred in 33% of children with bullous
      myringitis in comparison with 23% of control children with at least one event of
      AOM (RR 1.7; 95% CI, 1.01-2.7). The incidence of AOM in children with bullous
      myringitis was 1.8 per person year (95% CI, 1.4-2.2 per person year) before the
      event of bullous myringitis and 2.9 per person year (95% CI, 2.3-3.5 per person
      year) after the event of bullous myringitis. The higher incidence rate of AOM
      lasted for 2 months after the office visit of bullous myringitis. CONCLUSIONS:
      Acute bullous myringitis is not a rare disease; it was diagnosed in 5.7% of
      children <2 years in a 1-year follow-up. It was present in almost 1 of every 20
      AOM events. Acute bullous myringitis increases the subsequent risk of recurrent
      AOM.

PMID- 14597373
TI  - Performance of hearing impaired children on Raven's Coloured Progressive Matrices
      Test.
AB  - OBJECTIVE: Hearing impairment (HI) is presumed to influence the visual skills of
      affected children, possibly biasing their performance on tests requiring visual
      analyzing skills. We investigated whether such a bias would occur on Raven's
      Coloured Progressive Matrices (CPM); a set of three subtests (labeled A, AB and
      B) for measurement of non-verbal intelligence. METHOD: A sample of 62 children
      presenting with various degrees of HI were administered the test. Raw scores were
      controlled for age, and correlated to degree of HI. RESULTS: The correlation
      between degree of HI and overall test score missed significance (r=0.23, P=0.07),
      but scores from subtest B showed a significant positive correlation with HI
      (r=0.37, P=0.003). CONCLUSIONS: We conclude that severe or profound HI may lead
      to increased competence for task solution on subtest B. However, despite the
      biasing effect on this subtest, the CPM overall test score is only slightly
      affected.

PMID- 14597374
TI  - Endoscopic surgery in treatment of juvenile nasopharyngeal angiofibroma.
AB  - OBJECTIVES: Juvenile nasopharyngeal angiofibroma (JNA) is a highly vascular and
      locally invasive tumor with a high incidence of persistence and recurrence. The
      classical treatment of this tumor is surgery and/or radiotherapy. Use of
      endoscopic techniques seems to be on the rise in treatment of these lesions. We
      tried to explore the roles and limits of endoscopic surgery alone or with
      classical surgical techniques in treatment of these tumors. METHODS:
      Retrospective case review was conducted at a tertiary referral center. Twelve
      patients were treated for nasopharyngeal angiofibroma using endoscopic approach
      between 1998-2002. The staging, average blood loss during surgery, residual,
      and/or recurrent tumor were evaluated. RESULTS: Eight of these patients (8/12)
      were up to stage IIC according to Radkowski staging. This group of patients has
      an average blood loss of 1000 ml and were followed for at least 6 months. We did
      not encounter any residual or recurrent tumor in this group. Four patients (4/12)
      had minimal intracranial extension, were staged IIIA, and had an average blood
      loss of 1500 ml during surgery. Two of these patients had minimal residual tumor
      around the cavernous sinus, but showed no progression of disease over a follow-up
      of 2 years with MRI. Two patients had no residual or recurrent tumor over a
      follow-up of 6 months. CONCLUSION: This data suggests that endoscopic surgery can
      be used in the treatment of JNA even with minimal intracranial extension with
      minimal morbidity and low recurrence rate.

PMID- 14597375
TI  - Fourth branchial complex anomalies: a case series.
AB  - OBJECTIVE: Anomalies of the fourth branchial arch complex are exceedingly rare,
      with approximately forty cases reported in the literature since 1972. The authors
      report experience with six fourth arch anomalies. METHODS: Retrospective chart
      review of six consecutive patients presenting to the pediatric otolaryngology
      service at a tertiary care center with anomalies referable to the fourth
      branchial arch. RESULTS: All six patients presented within the first or second
      decade of life. All six had left-sided disease. Four patients presented with
      recurrent neck infection, one with asymptomatic cervical masses, and one with a
      neck mass and respiratory compromise. One patient had prior surgery presented
      with a recurrence. Diagnosis of fourth arch anomalies was suggested or confirmed
      by computed tomography and flexible laryngoscopy. Treatment was surgical in five
      patients; one patient is awaiting surgery. Surgical procedures included resection
      of the mass and endoscopic cauterization of the inner opening of the cyst.
      CONCLUSIONS: The presentation of a cervical mass, especially with recurrent
      infections and especially on the left side, in a child in the first or second
      decade of life heightens suspicion for an anomaly of the fourth branchial arch.
      Diagnosis can be difficult, but is aided by the use of flexible laryngoscopy,
      Computed tomography (CT) scanning and ultrasonography. Surgical resection of the
      cyst and cauterization of its pyriform sinus opening should be undertaken to
      minimize recurrence.

PMID- 14597376
TI  - The effect of a pneumococcal conjugate vaccine on the risk of otitis media with
      effusion at 7 and 24 months of age.
AB  - OBJECTIVE: To explore the effect of a pneumococcal conjugate vaccine on the risk
      of otitis media with effusion and to search for subgroups in which the vaccine
      had a higher or lower effect. METHODS: Analyses were performed on data from the
      Finnish Otitis Media Vaccine Trial, a randomised controlled double-blind trial to
      evaluate the efficacy of pneumococcal conjugate vaccination against acute otitis
      media. Data on the vaccination effect against otitis media with effusion were
      obtained by means of symptom interview and pneumatic otoscopy during pre
      scheduled follow-up visits at the age of 7 and 24 months. Two endpoint
      definitions were considered: otitis media/tube (otitis media or tympanostomy tube
      in situ (OM/T)) as the primary endpoint and otitis media with effusion as the
      secondary endpoint. No evidence was found of an age-dependent association with
      vaccination effect. Therefore, the final marginal logistic regression analyses
      were performed on the combined data from the two follow-up visits. RESULTS: The
      risk of otitis media tended to be lower in the pneumococcal vaccine group. The
      odds ratio for otitis media/tube was 0.94 (95% confidence interval 0.77-1.14) and
      the odds ratio for otitis media with effusion was 0.90 (95% confidence interval
      0.69-1.19). Presence of older siblings increased the risk of otitis media/tube
      and otitis media with effusion at 7 months of age. In addition, it appeared that
      children without older siblings and attending day-care at 24 months of age tended
      to benefit more from the pneumococcal conjugate vaccine. In this subgroup, the
      odds ratio for otitis media/tube was 0.81 (95% confidence interval 0.55-1.20) and
      for otitis media with effusion the odds ratio was 0.43 (95% confidence interval
      0.22-0.86). CONCLUSION: The effect of pneumococcal conjugate vaccination on the
      risk of otitis media with effusion was concordant with the efficacy seen against
      acute otitis media, although not distinguishable from no effect in the overall
      analysis. In children without older siblings, vaccination appeared to reduce the
      point prevalence of otitis media with effusion; this effect was not apparent in
      children with older siblings.

PMID- 14597377
TI  - Congenital mid-line cervical cleft: case report and review of literature.
AB  - Congenital Mid-line Cervical Cleft (CMCC) is a rare but interesting congenital
      anomaly of the neck that is frequently misdiagnosed. Much controversy exist
      regarding its aetiology. Embryologically, the occurrence of CMCC is thought to be
      due to many hypotheses that include impaired mid-line fusion of the first or
      second branchial arches, exteriorisation of a thyroglossal duct remnant, and or
      increased pressure in the cervical area from the pericardial roof in the
      developing embryo. Histologically, the cleft usually consists of a stratified
      keratinized squamous epithelium with hyperkeratosis, dermal fibrosis and little
      or no skin appendages. Associated clinical features could include thyroglossal
      duct cysts, cleft lip/mandible/sternum, cervical contractures, mandibular spurs,
      microgenia and or bronchogenic cysts. In this article we present a patient with
      CMCC. An extensive review of the literature is also included.

PMID- 14597378
TI  - Reticulohistiocytoma of the external auditory canal.
AB  - We report the first documented case of reticulohistiocytoma of the external
      auditory canal in a 15-year-old male. Reticulohistiocytoma is a rare diagnosis in
      children. Reticulohistiocytoma, a benign lesion, belongs to a family of
      histiocytosis disorders which range from benign to malignant. Although
      histiocytic disorders are uncommon, they should be included in differential
      diagnosis of pediatric aural polyps.

PMID- 14597379
TI  - Sphenoid sinus involvement in neuroblastoma: a case report and review of the
      literature.
AB  - Neuroblastoma is the most common extracranial solid tumors of childhood. The most
      frequent anatomic site of the primary tumor is abdomen. Metastatic spread of
      neuroblastoma to lymph node, bone, bone marrow and liver are common at
      presentation. However, primary or metastatic involvement of sphenoid sinus is
      extremely rare. Here, we report a case with stage IV neuroblastoma presents with
      the involvement of the sphenoid sinus. To our knowledge this is the fourth case
      of neuroblastoma involved sphenoid sinus in English literature.

PMID- 14597380
TI  - A unique case of an epidermoid cyst of the pterygopalatine fossa and its
      management.
AB  - Epidermoid cysts are rare benign tumors that are derived from the development of
      abnormally situated ectodermal tissue. Although they may originate from any part
      of the body head and neck region is occasionally affected. Epidermoid cyst
      originating from pterygopalatine fossa has not been reported previously in the
      literature. We report the first case of epidermoid cyst of pterygomaxillary fossa
      in this study.

PMID- 14597381
TI  - Severe sensory hearing loss in del(6q)-syndrome.
AB  - 6q-syndrome is a rare disorder characterised by a combination of anatomic
      anomalies, and mental and motor retardation due to a monosomy or trisomy 6q. So
      far only 12 suspected cases of monosomies 6q have been reported. Hearing loss
      does not seem to be characteristic for this syndrome. We present the case of a
      girl with partial monosomy 6q. A bilateral severe sensory hearing loss was
      confirmed by subjective and objective audiometry at the age of 12 years. The girl
      was successfully equipped with hearing aids. Other features of the syndrome, i.e.
      mental retardation, microcephaly, asymmetric face, broad nasal bridge,
      hypertelorism, epicanthus, strabism, high arched palate, ventricular septum
      defect and seizures were seen. Additionally, a tetraplegy and diaphragmal hernia
      had been diagnosed. The girl was equipped with a gastrostomy tube because of
      nutritional disorders. In the literature, the possibility of hearing disorders in
      monosomy 6q is rarely mentioned, although limited verbal speech skills have been
      reported. A syndromic character of hearing disorders in 6q-syndrome cannot be
      excluded. We advise detailed and early audiological testing of children with
      monosomy 6q.

PMID- 14597384
TI  - Transcriptional regulation by the MAP kinase signaling cascades.
AB  - A major function of the mitogen-activated protein kinase (MAPK) pathways is to
      control eukaryotic gene expression programmes in response to extracellular
      signals. MAPKs directly control gene expression by phosphorylating transcription
      factors. However, it is becoming clear that transcriptional regulation in
      response to MAPK signaling is more complex. MAPKs can also target coactivators
      and corepressors and affect nucleosomal structure by inducing histone
      modifications. Furthermore, multiple inputs into individual promoters can be
      elicited by MAPKs by targeting different components of the same coregulatory
      complex or by triggering different events on the same transcription factor.
      "Postgenomic approaches" are beginning to impact on our understanding of these
      gene regulatory networks. In this review, we summarise the current knowledge of
      MAPK-mediated gene regulation, and focus on how complexities in signaling
      outcomes are achieved and how this relates to physiological processes.

PMID- 14597385
TI  - Conservation of Sox4 gene structure and expression during chicken embryogenesis.
AB  - While mutations in Sox4, a member of the SRY-like HMG box gene family, have been
      associated with a variety of human disorders and embryonic defects in the mouse,
      the structure and developmental expression of Sox4 in the avian embryo has not
      been described. We have isolated and characterized the chicken Sox4 gene. The
      chicken Sox4 gene shows a high degree of sequence homology with the mouse and
      human Sox4 genes, particularly in the HMG-like DNA binding domain and at the
      carboxy terminus. Furthermore, our in situ hybridization studies document an
      expression pattern during embryonic development that is very similar to that
      described for the mouse, particularly with regards to expression in the
      developing heart. However, abundant expression was also detected in tissues of
      neural crest origin including pharyngeal arch and craniofacial mesoderm,
      supporting a potential primary role in neural crest cardiac pathology previously
      detected in Sox4 mutant mice. Furthermore, a reciprocal pattern of Sox4 and Sox11
      expression in the developing neural tube was detected in the chicken compared to
      that seen in the mouse. These studies suggest that Sox4 plays an important and
      conserved role in the embryonic development of these structures in the chicken as
      well as in the mouse and lay the foundation for future studies of the role of
      Sox4 during critical events of organogenesis.

PMID- 14597386
TI  - Identification of a novel member of the CLIC family, CLIC6, mapping to 21q22.12.
AB  - Five members of the newly identified chloride intracellular channel (CLIC) gene
      family of intracellular chloride channels (CLIC1-CLIC5) have previously been
      described in humans. Here we report the molecular cloning and initial
      characterisation of two splice forms of a novel member of this family, CLIC6,
      mapping to human chromosome 21. Two essential features distinguish CLIC6 from
      other members of the family. The CLIC6 protein is significantly longer and the
      CLIC6 gene contains a GC rich segment, which encodes a 10 amino acid motif
      repeated 14 times in the amino-terminus. Surprisingly, the repeat is conserved in
      the lagomorphs, but not in the rodents lineage. The putative bovine orthologue of
      CLIC5, p64, also exhibits a repeated motif, which is different from that of
      CLIC6. Attempts to functionally characterise CLIC6 by voltage clamp failed to
      show any chloride channel activity. Hence, the exact function of this protein
      remains unknown.

PMID- 14597387
TI  - Silencing the Drosophila ribosomal protein L14 gene using targeted RNA
      interference causes distinct somatic anomalies.
AB  - The Drosophila Minutes are haploinsufficient mutations that are defective in
      ribosomal protein (rp) production, resulting in short, thin bristles, delayed
      development and recessive lethality. In a Minute fly, the amount of rp gene
      messenger RNA (mRNA) is reduced to >or=50% of the normal amount of gene product,
      and becomes rate limiting for ribosome biogenesis, cell proliferation and growth.
      Haploinsufficiency increases the vulnerability to complete loss of gene function
      (homozygous null state) if hit by a second mutation. Because of the homozygous
      lethality, it has only been possible to study the effects of Minute mutations in
      heterozygous animals. To be able to study the consequences of a loss-of-function
      of an rp gene (0%>mRNA<50%) in developing and differentiated cells we used
      heritable RNA interference (RNAi) in combination with the yeast GAL4/UAS binary
      system to spatiotemporally knock down the ribosomal protein L14 (RpL14) gene. We
      show, at the RNA and phenotypic levels, that RNAi efficiently reduces RpL14 gene
      expression throughout development, causing lethality and distinct and dramatic
      somatic anomalies in both developing and differentiated cells.

PMID- 14597388
TI  - p63/73 homologues in surf clam: novel signaling motifs and implications for
      control of expression.
AB  - To understand the role of p53 gene family members during invertebrate embryonic
      development, we used polymerase chain reaction (PCR) to identify p63/73
      homologues in the marine mollusc Spisula solidissima. Here, we report the
      sequences of two distinct p63/73-like homologues, both cloned from Spisula
      embryos. The first, Ssp63/73alpha is 2699 nucleotide (nt); the second,
      Spp63/73beta is 3920 nt. The nucleotide sequences of the two variants are nearly
      identical up to their stop codons but diverge in their 3'-untranslated regions
      (UTRs). The deduced amino acid sequence of both Ssp63/73 variants is 597 amino
      acids, coding for a protein with predicted molecular weight of approximately 68
      kDa. We conclude that the two unique transcripts, containing 3' UTRs of variable
      lengths, represent tandem alternate polyadenylation sites for the Ssp63/73 gene.
      While alternative splicing has been well documented in the p63/73 gene family,
      this is the first report of alternate polyadenylation site choice as a control
      point for p63/73 gene expression in any species. In order to identify specific
      post-transcriptional as well as post-translational signals potentially involved
      in regulation of p63/73-like expression, we compared Ssp63/p73 nucleotide and
      Ssp63/73 deduced amino acid sequences to corresponding regions of other mammalian
      and nonmammalian p63 and p73 homologues. Within the Spisula 3' UTRs we identified
      multiple AU-rich elements (AREs) which may control translation activation. Within
      the deduced amino acid sequence, we identified potential sites for sumoylation, a
      post-translational process that has been identified in mammalian p63 and p73
      proteins. Identification of these novel signaling sites provides information
      about potential mechanisms controlling expression of multiple p63/73 isoforms
      during development.

PMID- 14597389
TI  - Characterization of cis-elements mediating the stimulation of glucose-6-phosphate
      transporter promoter activity by glucocorticoids.
AB  - The endoplasmatic glucose-6-phosphate transporter is involved in the control of
      hepatic glucose production and blood glucose homeostasis. In this study, the
      expression of a luciferase reporter gene under the control of the glucose-6
      phosphate transporter gene promoter was examined in transiently transfected
      hepatoma cells. The promoter activity was stimulated approximately 2.5-fold by
      dexamethasone. Mutational analyses demonstrated that the regions nucleotide (nt) 
      215/-209 and nt -197/-183 relative to the translation start site were critical
      for this regulation. In gel electrophoretic mobility shift assays the
      transcription factor Fox O1, also called forkhead in rhabdomyosarcoma (FKHR),
      overexpressed in 293 cells, bound to a probe with the sequence nt -215/-209. The
      overexpression of Fox O1 stimulated the induction of glucose-6-phosphate
      transporter promoter activity by dexamethasone via nt -215/-209 in hepatoma
      cells. Recombinant glucocorticoid receptor DNA binding domain protein bound to a
      probe with the sequence of nt -197/-183 in gel electrophoretic mobility shift
      assays and an oligonucleotide with this sequence transferred glucocorticoid
      responsiveness to a heterologous promoter. The data indicate that the glucose-6
      phosphate transporter promoter contains a glucocorticoid response unit consisting
      of binding sites for Fox O1 and the glucocorticoid receptor.

PMID- 14597390
TI  - De novo gene expression and antisense inhibition in cultured cells of BmTRN-1,
      cloned from the midgut of the silkworm, Bombyx mori, which is homologous with
      mammalian TIA-1/R.
AB  - A cDNA encoding a 388 amino acid TIA-1-type RNA-binding protein (BmTRN-1) was
      isolated from midgut cDNAs of the silkworm, Bombyx mori, via homologous cloning,
      in order to characterize its function. The deduced amino acid sequence, most
      likely encoded by a single copy gene, has significant homology with human TIA-1
      and TIAR known as apoptotic regulators and recently reported to function as
      important factors for either splicing or translation. RT-PCR analysis showed that
      the BmTRN-1 gene was vigorously transcribed in the midgut at the gut purge stage,
      indicating a possible relation to the tissue-decomposing process in larval-pupal
      metamorphosis. We also show that inhibition of the expression of BmTRN-1 by a
      transfected oligonucleotide encoding the antisense sequence caused a remarkable
      rise in protein expression from artificially constructed cDNAs encoded by plasmid
      vectors in Bombyx cells, depending on the constructed ORF sequences of the
      introduced cDNAs. Furthermore, it was shown that the transcripts from the cDNAs
      introduced into the cells increased under the antisense-inhibition of BmTRN-1
      when the protein levels of these cDNAs also rose, demonstrating that BmTRN-1
      could act as a regulator especially of the mechanism eliminating transcripts with
      possible targets for BmTRN-1 recognition in the authentic post-transcription
      process.

PMID- 14597391
TI  - Mutational analysis of the Acropora millepora PaxD paired domain highlights the
      importance of the linker region for DNA binding.
AB  - Pax transcription factors are found in animals, from simple sponges to insects
      and vertebrates. The defining feature of Pax proteins is the DNA-binding paired
      domain (PD), which consists of two helix-turn-helix subdomains, joined with a
      linker region. Despite high specificity in vivo, the paired domains of different
      Pax proteins bind similar consensus DNA sequences in vitro. Using bandshift
      techniques, we show here that the paired domain of the Acropora millepora PaxD
      protein, which unambiguously belongs to the Pax3/7 group, does not bind to three
      defined paired domain-binding sites. Domain swapping experiments and site
      directed mutagenesis identified two amino acid residues in the linker region of
      the paired domain as critical to DNA binding; G70 and S71 are highly conserved in
      Pax proteins, but differ in PaxD (L70 and N71). The PaxD data thus highlight the
      importance of the linker region, and particularly G70 and S71, in DNA binding by
      Pax proteins.

PMID- 14597392
TI  - Hierarchical structure of donor splice site sequence multitude.
AB  - An analysis of donor splice site sequence (dsss) multitude was carried out. A
      special method was developed to study the multitude properties. The multitude of
      dsss was arranged as a hierarchical tree where the "root" consists of a small
      group of "ancestors", VAGgtVAG (gt stands in the beginning of intron, V=C,A,G).
      Every ancestor has its own clan of "descendants" which represent point mutants of
      it. The latter are split into "progenies". The first progeny looks like point
      mutants of the ancestors, the second as one-point mutants of sequences of the
      first progeny, and so forth. This picture looks like a hierarchical phylogenetic
      tree. The most striking property of the multitude is the successive monotonic
      decrease in occurrences of the sequences from one progeny to another. It is shown
      that such results may be modeled by a virtual mutational process.

PMID- 14597393
TI  - Early divergence of the FtsZ1 and FtsZ2 plastid division gene families in
      photosynthetic eukaryotes.
AB  - Homologues of the bacterial cell division protein FtsZ are found in higher plants
      where they function as key components of the chloroplast division complex. In
      contrast to most bacteria that encode a single FtsZ protein, plants encode
      multiple proteins that group into two families, FtsZ1 and FtsZ2. Using new
      sequence data from a broad range photosynthetic organisms, we performed a series
      of analyses to better understand the evolutionary history of the plant FtsZ
      families. Multiple phylogenetic analyses strongly support the grouping of the
      plant FtsZ genes and proteins into distinct FtsZ1 and FtsZ2 clades. Protein
      features representing potentially significant functional differences between
      FtsZ1 and FtsZ2 are identified. Genomic structure comparisons show that exon
      length and intron position are conserved within each clade, but differ between
      the clades except at one position. Our data indicate that the divergence of the
      FtsZ1 and FtsZ2 families occurred long before the evolution of land plants,
      preceding the emergence of the green algae. The results are consistent with
      proposals that the two FtsZ families evolved distinct functions during evolution
      of the chloroplast division apparatus, and indicate that genetic and functional
      differentiation occurred much earlier than previously hypothesized.

PMID- 14597394
TI  - The strength of translational selection for codon usage varies in the three
      replicons of Sinorhizobium meliloti.
AB  - The genome of the nitrogen-fixing bacterium Sinorhizobium meliloti is composed of
      three replicons of 3.65 (chromosome), 1.35 (pSymA) and 1.68 Mb (pSymB),
      respectively. While the chromosome encodes for most of the housekeeping
      functions, the three elements may contribute to symbiosis, though pSymA is
      absolutely necessary for nodulation and nitrogen fixation, since it harbours all
      the characterized nodulation and symbiotic fixation genes. On the other hand, the
      majority of the sequences located in this megaplasmid are probably not expressed
      during the free-living stage of the organism. Since most of the sequences located
      in pSymA are transcribed only at the stage of bacteroids when most probably the
      fate of the bacterium is to die, the mutations occurring at this stage will not
      be fixed in the population. Therefore, if natural selection contributes to the
      codon usage pattern in this species, its effect will be much weaker for the genes
      placed in pSymA. A codon usage analysis of the genes comprising the three
      replicons is consistent with the conclusion that selection for translational
      speed shapes the codon usage of the two replicons which are important for
      competitive cell growth while the codon usage of the third replicon reflects
      primarily the mutational bias.

PMID- 14597395
TI  - MITF-M plays an essential role in transcriptional activation and signal
      transduction in Xiphophorus melanoma.
AB  - The teleost Xiphophorus provides a genetically well-described model system to
      study the molecular processes underlying melanoma formation. As transcriptional
      deregulation is a widespread phenomenon in many tumors, we have studied the
      regulation of melanoma-specific gene expression in this fish. A central regulator
      of melanocyte specific gene expression, which is also a marker for melanomas, is
      the transcription factor microphthalmia-associated transcription factor (MITF).
      One of its targets, the tyrosinase gene, codes for a key enzyme in the melanin
      synthesis pathway. We could show that the promoter of the medaka tyrosinase gene
      is highly active in the Xiphophorus melanoma cell line PSM (platyfish-swordtail
      melanoma) but not in non-melanoma cells. Functional dissection of the promoter
      revealed that three E-boxes are essential for its pigment cell-specific activity.
      These binding sites for basic helix-loop-helix transcription factors are
      recognized by a nuclear protein from the melanoma cell line PSM, most likely
      MITF, as its exogenous delivery could activate the promoter in non-melanoma
      cells. The use of specific signalling inhibitors demonstrated that the activity
      of the tyrosinase promoter is negatively regulated by the melanoma-inducing
      receptor tyrosine kinase Xmrk in PSM cells. This repression is mediated by
      MAPkinase and dependent on E-box integrity, again implicating the involvement of
      MITF. The cumulative evidence indicates that in Xiphophorus, Xmrk suppresses
      differentiation signals relayed by MITF as part of the transformation process
      finally resulting in melanoma formation.

PMID- 14597396
TI  - Involvement of sigma(H) and related sigma factors in glucose-dependent initiation
      of morphological and physiological development of Streptomyces griseus.
AB  - We cloned and characterized sigH encoding a stress-response sigma factor,
      sigma(H), of Streptomyces griseus. Nucleotide sequencing of the sigH gene cluster
      revealed an identical gene organization as in the orthologous region of
      Streptomyces coelicolor A3(2). Transcriptional analysis by S1 nuclease mapping
      showed the presence of three tandem promoters (P1-P3) that direct transcription
      of sigH. The activity of P1 was markedly reduced in a sigH-depleted mutant,
      suggesting its dependence on sigma(H). P1 was induced by addition of 0.7 M NaCl,
      and P2 was induced by heat shock at 45 degrees C or addition of 4% ethanol. The
      sigH mutant of S. griseus showed conditional defect in aerial mycelium formation
      and streptomycin production depending on high concentration of glucose (>2%).
      Meanwhile, the wild-type strain of S. griseus introduced with rshA encoding a
      probable anti-sigma factor for sigma(H) on a high-copy-number plasmid was unable
      to perform development on media containing 1% glucose while it showed wild-type
      phenotype on media containing 1% maltose. RshA inhibited the sigma(H)-dependent
      in vitro run-off transcription at P1, which confirmed its role as a negative
      regulator for sigma(H). Analysis of RshA-sigma interaction by an Escherichia coli
      two-hybrid system showed specific interaction of RshA with sigma(H) and two
      related sigma factors, sigma(L) and sigma(F). We speculate that the high copy
      number of rshA represses morphological and physiological development of S.
      griseus through simultaneous inactivation of sigma(H) and related stress-response
      sigma factors, which play an essential role in the onset of cellular
      differentiation and antibiotic production on glucose media.

PMID- 14597397
TI  - Human wild-type SEDL protein functionally complements yeast Trs20p but some
      naturally occurring SEDL mutants do not.
AB  - X-linked spondyloepiphyseal dysplasia tarda (SEDT, or SEDL) is a primary skeletal
      dysplasia affecting mostly spinal vertebral bodies and epiphyses. Previously, we
      have identified the SEDL gene and determined the spectrum of 21 different SEDL
      causing mutations. The SEDL gene is a highly conserved gene with an as yet
      unknown function. The yeast SEDL protein ortholog, Trs20p, has been isolated as a
      member of a large multi-protein complex ( approximately 10 proteins) called
      transport protein particle (TRAPP), which is involved in endoplasmic reticulum
      (ER)-to-Golgi transport. While the SEDL gene mutations cause a tissue-specific
      (epiphyses) and relatively mild phenotype, the Trs20p function is essential for
      the yeast cell. We now provide evidence that recombinant human SEDL protein is
      able to functionally complement the Saccharomyces cerevisiae TRS20 (TRAPP subunit
      20 gene) knockout mutant. This finding strongly supports the speculated conserved
      nature of the SEDL/Trs20p function. To shed further light on the SEDL/Trs20p
      protein function, five different naturally occurring SEDL gene mutations have
      been tested in complementation studies. While two truncation mutations (157delAT
      and C271T) and one missense mutation (G139T) were unable to rescue the trs20Delta
      lethal phenotype, two other missense mutations (C218T and T389A) did complement
      trs20Delta. Interestingly, there is no obvious correlation between the nature and
      position of the SEDL mutation and the clinical severity of the disorder among the
      human SEDL patients. Although the identification of complementing SEDL gene
      mutations may suggest the existence of subtle phenotypic differences among SEDL
      patients, it might also point towards the identification of SEDL protein
      residues/domains specific for normal, vertebrate bone growth.

PMID- 14597398
TI  - Identification of a core promoter and a novel isoform of the human TSC1 gene
      transcript and structural comparison with mouse homolog.
AB  - Tuberous sclerosis complex (TSC) is an autosomal dominant disorder with loci on
      chromosome 9q34.12 (TSC1) and chromosome 16p13.3 (TSC2). Genes for both loci have
      been isolated and characterized. The promoters of both genes have not been
      characterized so far and little is known about the regulation of these genes.
      This study reports the characterization of the human TSC1 promoter region for the
      first time. We have identified a novel alternative isoform in the 5' untranslated
      region (UTR) of the TSC1 gene transcript involving exon 1. Alternative isoforms
      in the 5'UTR of the mouse Tsc1 gene transcript involving exon 1 and exon 2 have
      also been identified. We have identified three upstream open reading frames
      (uORFs) in the 5'UTR of the TSC1/Tsc1 gene. A comparative study of the 5'UTR of
      TSC1/Tsc1 gene has revealed that there is a high degree of similarity not only in
      the sequence but also in the splicing pattern of both human and mouse TSC1 genes.
      We have used PCR methodology to isolate approximately 1.6 kb genomic DNA 5' to
      the TSC1 cDNA. This sequence has directed a high level of expression of
      luciferase activity in both HeLa and HepG2 cells. Successive 5' and 3' deletion
      analysis has suggested that a approximately 587 bp region, from position +77 to 
      510 from the transcription start site (TSS), contains the promoter activity.
      Interestingly, this region contains no consensus TATA box or CAAT box. However, a
      521-bp fragment surrounding the TSS exhibits the characteristics of a CpG island
      which overlaps with the promoter region. The identification of the TSC1 promoter
      region will help in designing a suitable strategy to identify mutations in this
      region in patients who do not show any mutations in the coding regions. It will
      also help to study the regulation of the TSC1 gene and its role in tumorigenesis.

PMID- 14597399
TI  - Functional characterization of the interacting domains of the positive
      coactivator PC4 with the transcription factor AP-2alpha.
AB  - The transcriptional positive cofactor 4 (PC4) physically interacts with the
      transcription factor, activator protein-2 (AP-2) alpha, and overexpression of PC4
      results in a relief of the AP-2 transcriptional self-interference, which is
      induced by high levels of AP-2alpha expression. PC4 was initially described as a
      DNA-binding protein that enhances the activator-dependent transcription of class
      II genes in vitro, but it was later shown that PC4 could also act as a potent
      repressor of transcription on specific DNA structures such as single-stranded
      (ss) DNA, DNA ends and heteroduplex DNA. To further explore the functional
      domains of PC4 and its ssDNA-binding effect in the interaction with AP-2alpha and
      on AP-2 transcriptional activity, we investigated the C-terminal domain of PC4
      (PC4-CTD) and several PC4 mutants in which the ssDNA binding function was
      interrupted. We found that the C-terminal domain of PC4 physically interacts with
      AP-2alpha and retains the function of full-length protein in relieving
      transcription self-interference of AP-2. A point-mutated form of PC4 within the C
      terminal domain beta-ridge, PC4 W89A, or a triple mutant in the beta2-beta3 loop
      of PC4, F77A/K78G/K80G, inactivate the ability of PC4 to bind AP-2alpha and to
      relieve the transcription self-interference of AP-2alpha. In addition, point
      mutated forms of AP-2alpha within the activation domain (AD) that inactivate AP-2
      transcription activity also lose their self-interference function. Our data
      suggest that the C-terminal domain of the transcription cofactor PC4 is critical
      for AP-2alpha transcriptional interference that is mediated by the activation
      domain of AP-2alpha.

PMID- 14597400
TI  - Barnacle: an assembly algorithm for clone-based sequences of whole genomes.
AB  - We propose an assembly algorithm Barnacle for sequences generated by the clone
      based approach. We illustrate our approach by assembling the human genome. Our
      novel method abandons the original physical-mapping-first framework. As we show,
      Barnacle more effectively resolves conflicts due to repeated sequences which is
      the main difficulty of the sequence assembly problem. In addition, we are able to
      detect inconsistencies in the underlying data. We present and compare our results
      on the December 2001 freeze of the public working draft of the human genome with
      NCBI's assembly (Build 28). The assembly of December 2001 freeze of the public
      working draft generated by Barnacle and the source code of Barnacle are available
      at (http://www.cs.rutgers.edu/~vchoi).

PMID- 14597401
TI  - A cDNA encoding a cold-induced glycine-rich RNA binding protein from Prunus avium
      expressed in embryonic axes.
AB  - A cDNA clone encoding a presumed full-length glycine-rich ribonucleic acid (RNA)
      binding protein was isolated from a lambda-ZAP Express cDNA library generated
      from primarily nondormant Prunus avium (wild cherry) embryonic axes. The cDNA,
      designated Pa-RRM-GRP1 (Prunus avium RNA recognition motif glycine-rich protein
      1), contains a single N-terminal RNA recognition motif (RRM) and single C
      terminal glycine-rich domain. The glycine-rich domain is unusually long at 91
      amino acids, 58 of which are glycines. The 534-base pair (bp) open reading frame
      (ORF) of this clone encodes a 178-amino-acid polypeptide with a predicted
      molecular weight of 17.33 kDa and pI of 7.84. Comparative sequence alignment of
      Pa-RRM-GRP1 reveals extensive homology to known and presumed glycine-rich RNA
      binding proteins from angiosperms and gymnosperms. Genomic Southern blot analysis
      suggests that this gene exists as a single copy in P. avium. Expression of this
      gene in P. avium embryonic axes during low-temperature dormancy-breaking
      treatments was studied and found to be induced by cold (3 degrees C) using real
      time PCR of total cDNA supported by Northern blot analysis of total RNA.
      Expression dropped during prolonged storage at 3 degrees C and was reduced to
      control levels by interruption of cold treatment by warming to 20 degrees C.

PMID- 14597402
TI  - The effective number of codons for individual amino acids: some codons are more
      optimal than others.
AB  - The aim of this study was to evaluate the codon bias using the effective number
      of codons for individual amino acids (N(c)(AA)) and to assess the codon bias in
      relation to the definition of optimal codons, using Escherichia coli as a model
      organism. We show that a general correlation exists between the effective number
      of codons (Ncirc(c)) or codon adaptation index (CAI) and N(c)(AA), but that this
      correlation is not equally strong for all amino acids within a degeneracy group.
      For example, leucine codons contribute more to Ncirc(c) and the codon adaptation
      index than serine codons. A possible explanation is that some optimal codons are
      more optimal than others, in terms of the selectional advantage they offer. This
      hypothesis is confirmed by further analysis on the correlations that exist
      between values for relative synonymous codon usage (RSCU), N(c)(AA), and the
      codon adaptation index.

PMID- 14597403
TI  - Transforming growth factor-beta1 inhibits tumor growth in a mouse melanoma model
      by down-regulating the plasminogen activation system.
AB  - The degradation of basement membranes by tumor cells involves secretion and
      activation of proteinases, such as matrix metalloproteinases (MMPs) and the
      plasminogen activation system (uPA, tPA, PAI-1), and results from an imbalance
      between their inhibitors and activators, controlled by various growth factors or
      cytokines. Among them, the TGF-beta family is one of the most intriguing because
      it has been reported either to decrease or promote cancer progression. In the
      present paper, we studied the effect of TGF-beta1 in a mouse melanoma model. In
      vivo, TGF-beta1 inhibited tumor growth after subcutaneous injection of B16F1
      cells in syngenic mice. In vitro, TGF-beta1 did not alter B16F1 cell
      proliferation, but strongly decreased their migration through Matrigel-coated
      membranes. The protease production was analyzed by zymography, Western blot, or
      RT-PCR. MMP-2 and TIMP-2 expression were not altered by TGF-beta1. In contrast,
      TGF-beta1 triggered a large decrease of uPA and tPA, as well as a decrease of uPA
      and uPAR mRNAs. By Western blot and RT-PCR analyses, TGF-beta1 was shown to
      induce a strong increase of PAI-1 synthesis. Collectively, these results suggest
      that TGF-beta1 may inhibit melanoma tumor growth by specifically decreasing
      plasmin activity of tumor cells and play a protective role during the earliest
      stages of tumor progression.

PMID- 14597404
TI  - B cell receptor directs the activation of NFAT and NF-kappaB via distinct
      molecular mechanisms.
AB  - BCR engagement initiates intracellular calcium ([Ca2+]i) mobilization which is
      critical for the activation of multiple transcription factors including NF-kappaB
      and NFAT. Previously, we showed that Bruton's tyrosine kinase (BTK)-deficient
      (btk-/-) B cells, which display a modestly reduced calcium response to BCR
      crosslinking, do not activate NF-kappaB. Here we show that BTK is also essential
      for the activation of NFAT following BCR engagement. Pharmacological mobilization
      of [Ca2+]i in BTK-deficient DT40 B cells (DT40.BTK) does not rescue BCR directed
      activation of NF-kappaB and only partially that of NFAT, suggesting existence of
      additional BTK-signaling pathways in this process. Therefore, we investigated a
      requirement for BTK in the production of diacylglycerol (DAG). We found that
      DT40.BTK B cells do not produce DAG in response to BCR engagement.
      Pharmacological inhibition of PKC isozymes and Ras revealed that the BCR-induced
      activation of NF-kappaB requires conventional PKCbeta, whereas that of NFAT may
      involve non-conventional PKCdelta and Ras pathways. Consistent with an essential
      role for BTK in the regulation of NFAT, B cells from btk-/- mice display
      defective expression of CD5, a gene under the control of NFAT. Together, these
      results suggest that BCR employs distinct BTK-dependent molecular mechanisms to
      regulate the activation of NF-kappaB versus NFAT.

PMID- 14597405
TI  - A method to determine the relative cAMP permeability of connexin channels.
AB  - Here we present a method by which gap junction-mediated intercellular diffusion
      of adenosine 3',5'-cyclic monophosphate (cAMP) molecules can be monitored in
      "real-time" and the cAMP permeability of different gap junction channels can be
      compared. Intercellular cAMP diffusion was investigated throughout this study in
      human HeLa cells coexpressing murine connexin45 and cyclic nucleotide-gated (CNG)
      ion channels. The CNG channels were used as cAMP sensors, since CNG channel
      activation led to an increase of the cytosolic Ca2+ concentration, which was
      monitored by Ca2+ imaging. A cAMP gradient was generated between two contacting
      cells by restricting the photolysis of caged cAMP to only one cell. The
      intercellular diffusion of cAMP was measured by the increase in Ca2+
      concentration in the neighboring cell. We developed a standardization procedure
      for the Ca2+ signal which allowed estimation of the amount of cAMP that diffused
      from cell to cell. The number of gap junction channels between each cell pair
      investigated was determined by double whole-cell patch-clamp measurements. On the
      basis of these data we calculated how many gap junction channels contributed to
      the diffusion of a certain amount of cAMP. The new method can be used to compare
      the selective permeabilities of different gap junction channels for cAMP and for
      cGMP which also activates the CNG channel.

PMID- 14597406
TI  - Inhibition of chemokine receptor function by membrane cholesterol oxidation.
AB  - Membrane cholesterol is required to maintain chemokine receptor conformation and
      function for CXCR4 and CCR5. We previously demonstrated that chemokines
      preferentially bind to receptors within lipid rafts, which are cholesterol- and
      sphingolipid-rich membrane microdomains. To further elucidate the role of
      cholesterol in chemokine receptor function, we examined the effects of membrane
      cholesterol oxidation by cholesterol oxidase (CO), which enzymatically converts
      cholesterol to 4-cholesten-3-one. Here, we demonstrate that CO treatment (0.25
      2.0 U/ml) of human T cells inhibits CXCL12 (SDF-1alpha) and CCL4 (MIP-1beta)
      binding to cell surface CXCR4 and CCR5, respectively, resulting in the inhibition
      of chemokine-mediated intracellular calcium mobilization and chemotaxis. The
      effects were significantly enhanced by cotreatment with low-dose sphingomyelinase
      (SMase) (0.125 mU/ml), which produced little inhibitory effect by itself. CO and
      SMase treatment also inhibited HIV-1 infection through CXCR4, but not virus
      replication. Similar to the removal of membrane cholesterol, CO/SMase treatment
      induced conformation changes in the chemokine receptors as detected by
      differential loss in binding of epitope-specific monoclonal antibodies. We
      conclude that the native form of cholesterol with the hydroxyl group at C3 is
      critical to CXCR4 and CCR5 conformation and function.

PMID- 14597407
TI  - Reduction of Htt inclusion formation in strains of Saccharomyces cerevisiae
      deficient in certain DNA repair functions: a statistical analysis of phenotype.
AB  - Saccharomyces cerevisiae has been used as a model system to examine the
      aggregation of the huntingtin protein (Htt), a well-established marker in the
      pathology of the triplet expansion disorder Huntington's disease (HD). Several
      genetic backgrounds, such as Deltahsp104, have proven to be refractory to
      inclusion formation through a process yet to be fully elucidated. These results
      have prompted a wide-ranging search for other mutant strains that exhibit a lower
      level of Htt aggregation. A novel assay system in which Htt is expressed as a
      fusion protein containing eGFP enables an analysis of aggregation and the factors
      that suppress it. We have examined several strains that are devoid of certain
      mismatch repair genes and find that some of these support a reduced level of
      inclusion body formation. We apply a detailed and stringent statistical analysis
      to the results obtained for all yeast strains that exhibit a definable phenotype.
      Such analyses should be useful and applicable to other in vivo analyses of
      related phenomena.

PMID- 14597408
TI  - Early stage-specific inhibitions of cardiomyocyte differentiation and expression
      of Csx/Nkx-2.5 and GATA-4 by phosphatidylinositol 3-kinase inhibitor LY294002.
AB  - Inhibition of phosphatidylinositol 3-kinase (PI3-kinase) has been reported to
      block cardiomyocyte differentiation. However, at which stage PI3-kinase plays
      this important role and what its molecular targets are remain unknown. To answer
      these questions, we induced cardiomyocyte differentiation of P19CL6 mouse
      embryonal carcinoma cells and investigated the activation of PI3-kinase by
      analyzing phospho-Akt. We also treated P19CL6 cells with the PI3-kinase-specific
      inhibitor LY294002 either continuously or at various time points and monitored
      the expression of cardiac contractile proteins and transcription factors. Most
      cells differentiated into sarcomeric myosin heavy chain (MHC)-positive
      cardiomyocytes on day 16 after induction. An increase in phospho-Akt was observed
      after induction and was maintained throughout the differentiation. LY294002
      treatment restricted to the phase from days 0 to 4 was sufficient to inhibit
      cardiomyocyte differentiation in a dose-dependent manner. In contrast, LY294002
      treatment either from days 4 to 8 or from days 8 to 12 did not cause significant
      changes in sarcomeric MHC expression. LY294002 treatment from days 0 to 4 also
      suppressed Csx/Nkx-2.5 and GATA-4 expression. These results demonstrate that PI3
      kinase becomes activated and plays a pivotal role at a very early stage of
      cardiomyocyte differentiation, possibly by modulating the expression of the
      cardiac transcription factors.

PMID- 14597409
TI  - Inactivation of Src family kinases inhibits angiogenesis in vivo: implications
      for a mechanism involving organization of the actin cytoskeleton.
AB  - Inhibition of angiogenesis could be a treatment strategy for diseases such as
      cancer, rheumatoid arthritis, and diabetic retinopathy. PP2 is a pharmacological
      inhibitor of Src family kinases and was found to inhibit FGF-2 induced
      angiogenesis in vivo. Experiments in vitro showed that PP2 inhibited invasive
      growth and sprouting of both endothelial and vascular smooth muscle cells into a
      fibrin matrix. PP2 inhibited the formation of lamellopodia and expression of
      kinase inactive c-Src reduced phosphorylation of cortactin and paxillin,
      suggesting a model in which Src kinases are involved in organization of the actin
      cytoskeleton. Consequently, endothelial cells expressing kinase inactive c-Src
      failed to spread and form cord-like structures on a collagen matrix. These data
      suggest that pharmacological inactivation of Src family kinases inhibits FGF-2
      stimulated angiogenesis by interference with organization of the actin
      cytoskeleton in both endothelial and vascular smooth muscle cells, which affects
      cell migration.

PMID- 14597410
TI  - Growth and differentiation potential of main- and side-population cells derived
      from murine skeletal muscle.
AB  - Skeletal muscle-derived CD34+/45- (Sk-34) cells were identified as a new
      candidate for stem cells. However, the relationship between Sk-34 cells and side
      population (SP) cells is unknown. Here, we demonstrate that Sk-34 cells prepared
      from murine skeletal muscles consist wholly of main-population (MP) cells. The Sk
      34 cells included only a few SP cells (1:1000, SP:MP). Colony-forming units of Sk
      34 cells of both SP and MP possessed the same potential to differentiate into
      adipocytes, endothelial, and myogenic cells and showed the same colony-forming
      activity (1.6%). In addition, the colony-forming units of the CD34-/45- (double
      negative: DN) population were found to begin CD34 expression and to possess the
      potential to differentiate into myogenic and endothelial cells. We also found
      that expression of CD34 antigen precedes MyoD expression during the myogenic
      process of DN cells. Furthermore, both Sk-34 and DN cell populations were mostly
      negative for CD73 (93-95%), whereas the CD45+ cell population was >25% positive
      for CD73, and this trend was also seen in bone marrow-derived CD45+ cells. These
      results indicate that the MP cell population is about 99.9% responsible for the
      reported in vitro myogenic-endothelial responses of skeletal muscle-derived
      cells.

PMID- 14597411
TI  - Overexpression of the immediate early gene fra-1 inhibits proliferation, induces
      apoptosis, and reduces tumourigenicity of c6 glioma cells.
AB  - Hexamethylene bisacetamide (HMBA)-induced growth inhibition and differentiation
      of the rat C6 glioma cell line were found to be accompanied by down-regulation of
      the constitutively expressed fra-1 gene. In order to check if the fra-1 gene down
      regulation was essential for HMBA's growth inhibitory effect, C6 cells were
      stably transfected with vector expressing fra-1 cDNA under CMV promoter in either
      sense or antisense orientation. Contrary to the expectations, fra-1
      overexpression was found to inhibit proliferation and induce morphological
      differentiation of C6 cells. Furthermore, all three differentiation inducers
      studied viz. dibutyryl cyclic AMP (dbcAMP), staurosporine, and HMBA have greater
      growth inhibitory effect on fra-1 overexpressing clones as compared to the
      parental C6 cells. dbcAMP and staurosporine not only inhibit proliferation but
      bring about complete apoptosis of fra-1 overexpressing clones. Spontaneous
      apoptosis is seen in fra-1 overexpressing clones especially in confluent
      cultures. fra-1 overexpression also results in substantial reduction in anchorage
      independent growth and tumourigenicity of C6 cells. Overexpression of fra-1
      leading to proliferation inhibition of C6 glioma cells is consistent with the
      concept that fra-1 functions as a negative regulator of AP-1 activity.

PMID- 14597412
TI  - Alternative patterns of transcription and translation of the ribosomal protein
      L32 mRNA in somatic and spermatogenic cells in mice.
AB  - The patterns of transcription and translation of the ribosomal protein L32
      (Rpl32) mRNA differ greatly in adult testis and somatic tissues. Northern blots
      reveal that the levels of Rpl32 mRNA are four- to five-fold higher in prepubertal
      and adult testes, and purified pachytene spermatocytes and round spermatids than
      in a variety of nongrowing adult somatic tissues. 5' RACE demonstrates that
      transcription in 8-day prepubertal testis, which lacks meiotic and haploid cells,
      strongly prefers the same start site in the 5' terminal oligopyrimidine tract (5'
      TOP) that is used is somatic cells. The 5' TOP is a cis element that inhibits
      translation of many mRNAs in nongrowing somatic cells. Although the sizes of
      deadenylated Rpl32 mRNAs are indistinguishable in somatic and spermatogenic
      cells, transcription initiates at 11 sites over a 31-nt segment in adult testis
      and approximately 62% of Rpl32 mRNAs lack a 5' TOP. In agreement with previous
      studies, low levels of cycloheximide increase the proportions and sizes of
      polysomes in absorbance profiles, and increase the proportions and sizes of
      polysomes translating four 5' TOP mRNA species including the Rpl32 mRNA in 8-day
      seminiferous tubules. In contrast, cycloheximide has little or no effect on the
      absorbance profiles and distribution of Rpl32 mRNA and 5' TOP mRNAs in adult
      seminiferous tubules. The failure of cycloheximide to increase the size of
      polysomes in adult seminiferous tubules implies a block in the pathway by which
      ribosomes are recruited onto translationally active mRNAs.

PMID- 14597414
TI  - Failure of lamin A/C to functionally assemble in R482L mutated familial partial
      lipodystrophy fibroblasts: altered intermolecular interaction with emerin and
      implications for gene transcription.
AB  - Familial partial lipodystrophy is an autosomal dominant disease caused by
      mutations of the LMNA gene encoding alternatively spliced lamins A and C.
      Abnormal distribution of body fat and insulin resistance characterize the
      clinical phenotype. In this study, we analyzed primary fibroblast cultures from a
      patient carrying an R482L lamin A/C mutation by a morphological and biochemical
      approach. Abnormalities were observed consisting of nuclear lamin A/C aggregates
      mostly localized close to the nuclear lamina. These aggregates were not bound to
      either DNA-containing structures or RNA splicing intranuclear compartments. In
      addition, emerin did not colocalize with nuclear lamin A/C aggregates.
      Interestingly, emerin failed to interact with lamin A in R482L mutated
      fibroblasts in vivo, while the interaction with lamin C was preserved in vitro,
      as determined by coimmunoprecipitation experiments. The presence of lamin A/C
      nuclear aggregates was restricted to actively transcribing cells, and it was
      increased in insulin-treated fibroblasts. In fibroblasts carrying lamin A/C
      nuclear aggregates, a reduced incorporation of bromouridine was observed,
      demonstrating that mutated lamin A/C in FPLD cells interferes with RNA
      transcription.

PMID- 14597413
TI  - Unique tissue-specific level of DNA nucleotide excision repair in primary human
      mammary epithelial cultures.
AB  - DNA repair is essential for the maintenance of genomic integrity and stability.
      Nucleotide excision repair (NER) is a major pathway responsible for remediation
      of damage caused by UV light, bulky adducts, and cross-linking agents. We now
      show that NER capacity is differentially expressed in human tissues. We
      established primary cultures of peripheral blood lymphocytes (PBLs: N = 33) and
      foreskin fibroblasts (FF: N = 6), as well as adult breast tissue (N = 22) using a
      unique culture system, and measured their NER capacity using the unscheduled DNA
      synthesis (UDS) functional assay. Relative to FF, primary cultures of breast
      cells exhibited only 24.6 +/- 2.1% of NER capacity and PBLs only 8.9 +/- 1.2%.
      Cells from the breast therefore have a unique and distinctive DNA repair
      capacity. The NER capacities of all three cell types had similar coefficients of
      variation in the range of 10%-15%, which should be taken into account when
      running controls for this contextual assay. Unlike previous studies and
      speculation in the field, we found that NER was not affected by cell morphology,
      donor age, or proliferation as measured by the S phase index. While the NER
      capacity of the transformed lymphoblastoid cell line TK6 was within the range of
      our PBL samples, the breast tumor-derived MDA MB-231 cell line was four-fold
      higher than normal breast tissue. These studies show that analysis of baseline
      DNA repair in normal human cell types is critical as a basis for evaluation of
      the effects of "mutator" genes as etiological factors in the development of
      cancer.

PMID- 14597415
TI  - The cyclin D3-CDK4-p27kip1 holoenzyme in thyroid epithelial cells: activation by
      TSH, inhibition by TGFbeta, and phosphorylations of its subunits demonstrated by
      two-dimensional gel electrophoresis.
AB  - The cAMP-dependent mitogenic stimulation elicited by thyroid-stimulating hormone
      (TSH) in primary cultures of canine thyroid epithelial cells is unique as it
      upregulates the cyclin-dependent kinase (CDK) inhibitor p27kip1 but not D-type
      cyclins. TSH and cAMP promote the assembly of required cyclin D3-CDK4 complexes
      and their nuclear import. Here, the nuclear translocation of these complexes
      strictly correlated in individual cells with the enhanced presence of nuclear
      p27. p27, like cyclin D3, supported the TSH-stimulated pRb-kinase activity of the
      CDK4 complex and, as demonstrated using the high-resolution power of the two
      dimensional (2D) gel electrophoresis, the phosphorylation of CDK4, presumably by
      the nuclear CDK-activating kinase. In the presence of TSH, transforming growth
      factor beta (TGFbeta) did not affect the assembly of cyclin D3-CDK4, but it
      strongly inhibited the pRb-kinase activity associated with both cyclin D3 and
      p27, not only by preventing the nuclear import of cyclin D3-CDK4 and its binding
      to p27, but also by inhibiting CDK4 phosphorylation within residual p27-bound
      cyclin D3-CDK4 complexes. No alterations of the relative abundance of multiple
      (un)phosphorylated forms of cyclin D3 and p27 demonstrated by 2D-gel
      electrophoresis were associated with these processes. This study suggests a
      crucial positive role of p27 in the TSH-stimulated nuclear import,
      phosphorylation, and catalytic activity of cyclin D3-bound CDK4. Moreover, it
      demonstrates a technique to directly assess the in vivo phosphorylation of
      endogenous CDK4, which might appear as a last regulated step targeted by the
      antagonistic cell cycle effects of TSH and TGFbeta.

PMID- 14597417
TI  - Membrane type-1 matrix metalloproteinase (MT1-MMP) processing of pro-alphav
      integrin regulates cross-talk between alphavbeta3 and alpha2beta1 integrins in
      breast carcinoma cells.
AB  - We have recently demonstrated that in breast carcinoma MCF7 cells MT1-MMP
      processes the alphav, alpha3, and alpha5 integrin precursors generating the
      respective mature S-S-linked heavy and light alpha-chains. The precursor of
      alpha2 integrin subunit was found resistant to MT1-MMP proteolysis. The
      processing of the alphav subunit by MT1-MMP facilitated alphavbeta3-dependent
      adhesion, activation of FAK signaling pathway, and migration of MCF7 cells on
      vitronectin. To elucidate further the effects of MT1-MMP on cellular integrins,
      we examined the functional activity of alpha5beta1 and alpha2beta1 integrins in
      MCF7 cells expressing MT1-MMP. Either expression of MT1-MMP alone or its
      coexpression with alphavbeta3 failed to affect the functionality of alpha5beta1
      integrin, and adhesion of cells to fibronectin. MT1-MMP, however, profoundly
      affected the cross-talk involving alphavbeta3 and alpha2beta1 integrins. In MT1
      MMP-deficient cells, integrin alphavbeta3 suppressed the functional activity of
      the collagen-binding alpha2beta1 integrin receptor and diminished cell adhesion
      to type I collagen. Coexpression of MT1-MMP with integrin alphavbeta3 restored
      the functionality of alpha2beta1 integrin and, consequently, the ability of MCF7
      cells to adhere efficiently to collagen. We conclude that the MT1-MMP-controlled
      cross-talk between alphavbeta3 and alpha2beta1 integrins supports binding of
      aggressive, MT1-MMP-, and alphavbeta3 integrin-expressing malignant cells on type
      I collagen, the most common substratum of the extracellular matrix.

PMID- 14597418
TI  - Cell-cycle-dependent three-dimensional redistribution of nuclear proteins, P 120,
      pKi-67, and SC 35 splicing factor, in the presence of the topoisomerase I
      inhibitor camptothecin.
AB  - Topoisomerase I (Topo I) is mostly known for its role in DNA relaxation, which is
      required for duplication and transcription. Topo I acts as a protein kinase
      mainly directed to the mRNA splicing factor SC35. Camptothecin is one of the
      specific Topo I inhibitors and is effective on the two functions of the enzyme.
      In this study we demonstrated that treatment of KB cells with camptothecin for
      only 30 min induced the 3D reorganization and redistribution of three proteins
      involved in the nucleus machinery, P 120, pKi-67, and SC 35, and this occurred in
      a cell cycle-dependent manner. Our data were obtained from confocal microscopic
      studies after immunolabeling, 3D reconstruction, and measurement of the nuclear
      components volumes. In the presence of camptothecin, P 120, which occupied the
      nucleolar volume, lost its reticulation and pKi-67 was redistributed within the
      nucleoplasm and even into the cytoplasm. Finally, for SC 35 the fusion of its
      dots into bigger volumes was observed specifically during the G1 phase.
      Variations of volumes were also observed for the nucleolus and for the nucleus.
      These results pointed out that, depending on the cell cycle phase, Topo I
      functions were selective toward the three different proteins.

PMID- 14597419
TI  - Regulation of endothelial cell differentiation and transformation by H-Ras.
AB  - Angiogenesis is regulated by growth factors which activate tyrosine kinase
      receptors leading to the activation of a number of intracellular signaling
      pathways. The specific function of H-Ras during FGF-2 stimulated endothelial cell
      differentiation, defined as invasive growth and formation of branching networks
      in fibrin gels, was investigated by using conditionally immortalized endothelial
      cell lines induced to express H-Ras mutants. Expression of inhibitory N17Ras did
      not impair differentiation in response to FGF-2 and TNF-alpha. The
      farnesyltransferase inhibitor FTI-277 inhibited farnesylation of Ras but did not
      inhibit differentiation of human microvascular endothelial cells or mouse brain
      endothelial cells. In contrast, activated V12Ras inhibited endothelial cell
      differentiation and cells displayed a transformed phenotype with an increased
      rate of proliferation and loss of contact inhibited growth. Furthermore, V12Ras
      expressing endothelial cells grew as solid tumors when injected subcutaneously
      into mice. Our data suggest that, in endothelial cells, H-Ras activity is not
      required for differentiation. However, this activity must be tightly regulated as
      aberrant activity can disturb the ability of endothelial cells to undergo
      differentiation.

PMID- 14597416
TI  - Regulation of membrane trafficking and subcellular organization of endocytic
      compartments revealed with FM1-43 in resting and activated human T cells.
AB  - FM1-43, a fluorescent styryl dye that penetrates into and stains membranes, was
      used to investigate kinetics of constitutive endocytosis and to visualize the
      fate of endocytic organelles in resting and activated human T lymphocytes. The
      rate of dye accumulation was strongly temperature dependent and approximately 10
      fold higher in activated than in resting T cells. Elevation of cytosolic free
      Ca2+ concentration with thapsigargin or ionomycin further accelerated the rate of
      FM1-43 accumulation associated with cytosolic actin polymerization. Direct
      modulation of actin polymerization affected membrane trafficking. Actin
      condensation beneath the plasma membrane with calyculin A abolished FM1-43
      internalization, whereas actin depolymerization with cytochalasin D had no
      effect. Photoconversion of DAB by FM1-43 revealed altered endocytic compartment
      targeting associated with T cell activation. Internalized cargo was carried to
      lysosome-like compartments in resting T cells and to multivesicular bodies (MVB)
      in activated T cells. Externalization of exosomes from MVB occurred commonly in
      activated but not in resting T cells. T cell exosomes contained raft-associated
      CD3 proteins, GM1 glycosphingolipids, and phosphatidylserine at the outer
      membrane leaflet. The present study demonstrates the utility of FM1-43 as a
      marker of membrane trafficking in T cells and reveals possible mechanisms of its
      modulation during T cell activation.

PMID- 14597420
TI  - Activation of p38 and Smads mediates BMP-2 effects on human trabecular bone
      derived osteoblasts.
AB  - The bone morphogenetic proteins (BMPs) are potent osteoinductive factors that
      accelerate osteoblast maturation, accompanied by increased cell-substrate
      adhesion. BMP-2 treatment of osteoblastic cells increases phosphorylation of the
      cytoplasmic BMP-2 signaling molecules, Smad1 and Smad5. We have previously
      reported that BMP-2 treatment increase cytoskeletal organization of human
      trabecular bone-derived osteoblast-like cells (osteoblasts), which is also
      accompanied by an activation of the focal adhesion kinase p125(FAK). We report
      here that activation of p125(FAK) occurs with the same kinetics as the
      phosphorylation of Smad1, suggesting that BMP-2 initiates cross-talk between Smad
      signaling and the adhesion-mediated signaling pathway. As an adjunct to these
      effects, we examined activation of mitogen-activated protein (MAP) kinase family
      members in response to focal adhesion contact formation. Although phosphorylated
      forms of all three kinases were apparent, only SAPK2alpha/p38 (p38) was activated
      in response to BMP-2 treatment. Inhibition of p38 kinase activity suppressed BMP
      2 induced Smad1 phosphorylation, as well as its translocation to the nucleus,
      suggesting the integration of p38 activation with Smad1 signaling. Finally,
      inhibition of p38 in osteoblasts also led to the complete abrogation of BMP-2
      induced osteocalcin gene expression and matrix mineralization. These findings
      suggest that BMP-2 must activate p38 in order to mediate osteogenic
      differentiation and maturation.

PMID- 14597421
TI  - Novel binding sites of 15-deoxy-Delta12,14-prostaglandin J2 in plasma membranes
      from primary rat cortical neurons.
AB  - 15-Deoxy-Delta12,14-prostaglandin J2 (15d-Delta12,14-PGJ2) is an endogenous
      ligand for a nuclear peroxysome proliferator activated receptor-gamma (PPAR). We
      found novel binding sites of 15d-Delta12,14-PGJ2 in the neuronal plasma membranes
      of the cerebral cortex. The binding sites of [3H]15d-Delta12,14-PGJ2 were
      displaced by 15d-Delta12,14-PGJ2 with a half-maximal concentration of 1.6 microM.
      PGD2 and its metabolites also inhibited the binding of [3H]15d-Delta12,14-PGJ2.
      Affinities for the novel binding sites were 15d-Delta12,14-PGJ2 > Delta12-PGJ2 >
      PGJ2 > PGD2. Other eicosanoids and PPAR agonists did not alter the binding of
      [3H]15d-Delta12,14-PGJ2. In primary cultures of rat cortical neurons, we examined
      the pathophysiologic roles of the novel binding sites. 15d-Delta12,14-PGJ2
      triggered neuronal cell death in a concentration-dependent manner, with a half
      maximal concentration of 1.1 microM. The neurotoxic potency of PGD2 and its
      metabolites was also 15d-Delta12,14-PGJ2 > Delta12-PGJ2 > PGJ2 > PGD2. The
      morphologic and ultrastructural characteristics of 15d-Delta12,14-PGJ2-induced
      neuronal cell death were apoptotic, as evidenced by condensed chromatin and
      fragmented DNA. On the other hand, we detected little neurotoxicity of other
      eicosanoids and PPAR agonists. In conclusion, we demonstrated that novel binding
      sites of 15d-Delta12,14-PGJ2 exist in the plasma membrane. The present study
      suggests that the novel binding sites might be involved in 15d-Delta12,14-PGJ2
      induced neuronal apoptosis.

PMID- 14597422
TI  - Surface expression of heterogeneous nuclear RNA binding protein M4 on Kupffer
      cell relates to its function as a carcinoembryonic antigen receptor.
AB  - Elevated concentrations of carcinoembryonic antigen (CEA) in the blood are
      associated with the development of hepatic metastases from colorectal cancers.
      Clearance of circulating CEA occurs through endocytosis by liver macrophages,
      Kupffer cells. Previously we identified heterogeneous nuclear ribonucleoproteins
      M4 (hnRNP M4) as a receptor (CEAR) for CEA. HnRNP M4 has two isoform proteins
      (p80, p76), the full-length hnRNP M4 (CEARL) and a truncated form (CEARS) with a
      deletion of 39 amino acids between RNA binding domains 1 and 2, generated by
      alternative splicing. The present study was undertaken to clarify any isoform
      specific differences in terms of their function as CEA receptor and localization.
      We develop anti-CEAR isoform-specific antibodies and show that both CEAR splicing
      isoforms are expressed on the surface of Kupffer cells and can function as CEA
      receptor. Alternatively, in P388D1 macrophages CEARS protein has nuclear and
      CEARL has cytoplasmic localization. In MIP101 colon cancer and HeLa cells the
      CEARS protein is localized to the nucleus and CEARL to the cytoplasm. These
      findings imply that different functions are assigned to CEAR isoforms depending
      on the cell type. The search of 39 amino acids deleted region against the Prosite
      data base revealed the presence of N-myristylation signal PGGPGMITIP that may be
      involved in protein targeting to the plasma membrane. Overall, this report
      demonstrates that the cellular distribution, level of expression, and relative
      amount of CEARL and CEARS isoforms determine specificity for CEA binding and the
      expression of alternative spliced forms of CEAR is regulated in a tissue-specific
      manner.

PMID- 14597423
TI  - The Us3 protein kinase of herpes simplex virus 1 blocks apoptosis and induces
      phosporylation of the Bcl-2 family member Bad.
AB  - Viruses have evolved different strategies to interfere with apoptotic pathways in
      order to halt cellular responses to infection. The herpes simplex virus 1 (HSV-1)
      Us3 open-reading frame encodes a serine/threonine protein kinase that
      participates in the inhibition of apoptosis induced by virus infection and other
      stress agents. Previous studies have shown that Us3 counteracts the virus-induced
      activation of caspase-3 by acting at a premitochondrial stage. Using stable
      transfectants that express Us3 under the control of constitutive or inducible
      promoters we demonstrate that apoptosis induced by treatment with anti-Fas
      antibody and sorbitol is blocked when Us3 is expressed at levels comparable to
      those achieved during virus infection. Expression of Us3 correlated with
      phosphorylation of Bad, a BH3-only proapoptotic Bcl-2 family member that is also
      a target for growth factor-induced cellular kinases. Bad was phosphorylated by
      Us3 in in vitro kination assays. These results point to a strategy for viral
      inhibition of apoptosis based on functional inactivation of a critical component
      of the cellular death machinery.

PMID- 14597425
TI  - A method for describing the canopy architecture of coppice poplar with allometric
      relationships.
AB  - A multi-scale biometric methodology for describing the architecture of fast
      growing short-rotation woody crops is used to describe 2-year-old poplar clones
      during the second rotation. To allow for expressions of genetic variability
      observed within this species (i.e., growth potential, leaf morphology, coppice
      and canopy structure), the method has been applied to two clones: Ghoy (Gho)
      (Populus deltoides Bartr. ex Marsh. x Populus nigra L.) and Trichobel (Tri)
      (Populus trichocarpa Torr. & A. Gray x Populus trichocarpa). The method operates
      at the stool level and describes the plant as a collection of components (shoots
      and branches) described as a collection of metameric elements, themselves defined
      as a collection of elementary units (internode, petiole, leaf blade). Branching
      and connection between the plant units (i.e., plant topology) and their spatial
      location, orientation, size and shape (i.e., plant geometry) describe the plant
      architecture. The methodology has been used to describe the plant architecture of
      15 selected stools per clone over a 5-month period. On individual stools, shoots
      have been selected from three classes (small, medium and large) spanning the
      diameter distribution range. Using a multi-scale approach, empirical allometric
      relationships were used to parameterize elementary units of the plant,
      topological relationships and geometry (e.g., distribution of shoot diameters on
      stool, shoot attributes from shoot diameter). The empirical functions form the
      basis of the 3-D Coppice Poplar Canopy Architecture model (3-D CPCA), which
      recreates the architecture and canopy structure of fast-growing coppice crops at
      the plot scale. Model outputs are assessed through visual and quantitative
      comparisons between actual photographs of the coppice canopy and simulated
      images. Overall, results indicate a good predictive ability of the 3-D CPCA
      model.

PMID- 14597424
TI  - Oxidative stress-induced apoptosis is mediated by ERK1/2 phosphorylation.
AB  - Oxidative stress is known to induce apoptosis in a wide variety of cell types,
      apparently by modulating intracellular signaling pathways. High concentrations of
      H2O2 have been found to induce apoptosis in L929 mouse fibroblast cells. To
      elucidate the mechanisms of H2O2-mediated apoptosis, ERK1/2, p38-MAPK, and JNK1/2
      phosphorylation was examined, and ERK1/2 and JNK1/2 were found to be activated by
      H2O2. Inhibition of ERK1/2 activation by treatment of L929 cells with PD98059 or
      dominant-negative ERK2 transfection blocked H2O2-induced apoptosis, while
      inhibition of JNK1/2 by dominant-negative JNK1 or JNK2 or MKK4 or MKK7
      transfection did not affect H2O2-mediated apoptosis. H2O2-mediated ERK1/2
      activation was not only Ras-Raf dependent, but also both tyrosine kinase
      (PDGFbeta receptor and Src) and PKCdelta dependent. H2O2-mediated PKCdelta
      dependent and tyrosine kinase-dependent ERK1/2 activations were independent from
      each other. Based on the above results, we suggest for the first time that
      oxidative damage-induced apoptosis is mediated by ERK1/2 phosphorylation which is
      not only Ras-Raf dependent, but also both tyrosine kinase and PKCdelta dependent.

PMID- 14597426
TI  - Predicting leaf area index from scaling principles: corroboration and
      consequences.
AB  - Leaf area index (LAI) is a key biophysical variable in most process-based forest
      ecosystem models. However, most such models require LAI as an input, typically
      obtained from empirical observations. We tested whether scaling principles based
      on trade-offs between single leaf and canopy properties could be effectively used
      to model LAI, thereby obviating the need for empirical observations. To do so, we
      used the process-oriented model, PnET, configured to estimate LAI from these same
      scaling principles. We derived biologically based LAI predictions (LAIPnET) for
      the Harvard Forest (Massachusetts, USA) eddy covariance tower site, a
      predominately mixed deciduous hardwood forest, using PnET, and compared these
      with a locally observed phenology record and with LAI estimates from both local
      (ground-based) photosynthetically active radiation transmittance (LAITRANS) and
      normalized difference vegetation index satellite data (LAINDVI). We generated the
      LAIPnET trajectory by running the PnET model with meteorological observations
      from the flux tower as model drivers. We derived LAITRANS from measurements of
      above- and below-canopy photosynthetically active radiation at the flux tower,
      and LAINDVI from observations from the Advanced Very High Resolution Radiometer
      (AVHRR) satellite-borne sensor of surface greenness for the 1 km2 cell containing
      the flux tower. Over a 5-year period, LAIPnET and LAITRANS values were comparable
      intra- and interannually, with maximum values differing by less than 0.1 to 0.2
      LAI units (m2 m(-2)). Values of LAINDVI were similar to LAIPnET and LAITRANS in
      midsummer, but higher LAI values were predicted in the early and late portions of
      the growing season. In addition, we used the three alternative LAI trajectories
      in a modified version of the PnET model and compared the resulting outputs of
      gross primary production (GPP) with GPP estimates from the flux tower for 5
      continuous years. The LAIPnET and LAITRANS inputs resulted in a difference of
      less than 3% in mean annual GPP from 1995 to 1999, and these were within 7 and
      9%, respectively, of the annual eddy flux-based estimates over the same time
      period. The results indicate that biologically based LAI scaling approaches can
      closely track temporal changes in a deciduous forest and have potential for
      spatial and temporal scaling of LAI.

PMID- 14597428
TI  - Response of Douglas-fir seedlings to a brief pulse of 15N-labeled nutrients.
AB  - The temporal distribution of soil nutrients is heterogeneous, and thus the
      uptake, storage and later remobilization of brief nutrient pulses may be critical
      for growth in nutrient-limited habitats. We investigated the response of 2-year
      old Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco) seedlings receiving a low
      nutrient supply to a 15-day nutrient pulse (containing 250 ppm nitrogen (N) as 10
      atom % 15NH4 15NO3). The nutrient pulse was imposed in late July, toward the end
      of the seedlings' third growing season, and subsequent changes in dry mass and N
      content over the following 3 months were determined from destructive harvests. We
      tested three hypotheses: (1) N from the nutrient pulse is rapidly assimilated and
      accumulated primarily in needles and roots; (2) this accumulated N is later
      remobilized to support new growth; and (3) the nutrient pulse leads to a larger
      second flush of shoot growth. Seedlings increased their N content by 175 mg (67%)
      in response to the nutrient pulse. Nitrogen was taken up preferentially into
      younger tissues, especially the secondary flush and current-year roots.
      Immediately after the nutrient pulse, tissue N concentrations were high and
      supported subsequent increases in dry mass. Over 3 months, seedlings receiving
      the nutrient pulse added twice as much dry mass as control seedlings, and even
      after 3 months of growth, N concentrations remained greater than in controls.
      Current-year and older needles were the only components whose dry mass did not
      increase over this period. The nutrient pulse increased the size of the second
      flush, but it was still a minor component of increments in dry mass
      (approximately 10% of the total dry mass increment) and N content (23%). The
      relatively modest increases in N content during autumn could be accounted for by
      soil uptake and there was no evidence that N was remobilized to support growth of
      new tissues. Short-term (15 days) elevated N uptake led to sustained growth in
      the long term (> 3 months), and thus growth rate was to a large extent decoupled
      from current nutrient supply.

PMID- 14597427
TI  - Aux/IAA gene family is conserved in the gymnosperm, loblolly pine (Pinus taeda).
AB  - We isolated five members of the Aux/IAA gene family in loblolly pine (Pinus taeda
      L.). Degenerate primers complementary to conserved regions of angiosperm Aux/IAA
      genes were used to amplify fragments that were, in turn, used as probes to screen
      a cDNA library constructed from auxin-treated hypocotyls. The five unique clones,
      named PTIAA1-5, contain the four highly conserved domains that are characteristic
      of the Aux/IAA proteins. All clones contain the bipartite nuclear localization
      signal (NLS) between Domains I and II that is predicted in most angiosperm
      Aux/IAA genes, but only one, PTIAA2, contains the conserved NLS in Domain IV. The
      five invariant residues in Domain II that have been found to constitute part of a
      protein destabilization element in Arabidopsis thaliana (L.) Heynh. are conserved
      in all the PTIAAs. A postulated phosphorylation site located between Domains I
      and II and proximal to the conserved bipartite NLS was conserved in 20 out of 36
      genes in this analysis, including the pine genes. Transcripts of all five PTIAAs
      accumulated specifically in the hypocotyls in response to exogenous auxin
      treatment and were induced by all auxins tested. Transcript abundance above basal
      levels in response to 1-naphthaleneacetic acid treatment was first detected after
      10 min (PTIAA3) to 3 h (PTIAA2) in the different genes and remained above basal
      levels throughout 7 days. Induction of PTIAA2 was inhibited by the protein
      synthesis inhibitor cycloheximide, indicating that PTIAA2 is a secondary response
      gene. Phylogenetic analysis showed that all five pine genes clustered within a
      single class (Class I) of the dendrogram. Clone PTIAA2 has a sequence that is
      relatively distinct from the other four and is the most closely related to the
      angiosperm genes of Class I. Class I contains both primary and secondary auxin
      response genes, suggesting that it is the original lineage and that other gene
      classes have evolved subsequent to the angiosperm/gymnosperm divergence.

PMID- 14597429
TI  - Early developmental responses of mountain birch (Betula pubescens subsp.
      czerepanovii) seedlings to different concentrations of phosphorus.
AB  - Phenolic compounds, identified by high performance liquid chromatography (HPLC),
      and growth were investigated in the first true leaves, cotyledons, stems and
      roots of 2.5-week-old seedlings of mountain birch (Betula pubescens subsp.
      czerepanovii (Orlova) Hametahti) grown with 1.5, 15 and 50 ppm phosphorus (P).
      Phenolic compounds in seeds and unfertilized 6-day-old seedlings were also
      studied. Seeds contained few phenolics, but had an abundance of condensed
      tannins. There were fewer HPLC phenolic compounds in 6-day-old seedlings than in
      2.5-week-old seedlings. In 2.5-week-old seedlings, growth of the first true
      leaves, but not of other plant parts, was affected by P regime. In the first true
      leaves and stems, the concentration of condensed tannins was significantly
      affected by P, being higher at 1.5 ppm than at higher concentrations. The
      concentration of total HPLC phenolics was significantly affected by P only in
      stems.

PMID- 14597430
TI  - Factors influencing Agrobacterium-mediated embryogenic callus transformation of
      Valencia sweet orange (Citrus sinensis) containing the pTA29-barnase gene.
AB  - Valencia sweet orange (Citrus sinensis (L.) Osbeck) calluses were used as
      explants to develop a new transformation system for citrus mediated by
      Agrobacterium tumefaciens. Factors affecting Agrobacterium-mediated
      transformation efficiency included mode of pre-cultivation, temperature of
      cocultivation and presence of acetosyringone (AS). The highest transformation
      efficiency was obtained with a 4-day pre-cultivation period in liquid medium.
      Transformation efficiency was higher when cocultivation was performed for 3 days
      at 19 degrees C than at 23 or 28 degrees C. Almost no resistant callus was
      obtained if the cocultivation medium lacked AS. The transformation procedure
      yielded transgenic Valencia plants containing the pTA29-barnase gene, as verified
      by PCR amplification and confirmed by Southern blotting. Because male sterility
      is a common factor leading to seedlessness in citrus cultivars with
      parthenocarpic characteristics, production of seedless citrus genotypes by
      Agrobacterium-mediated genetic transformation is a promising alternative to
      conventional breeding methods.

PMID- 14597431
TI  - Thinning effects on carbon allocation to fine roots in a Quercus ilex forest.
AB  - The dynamics of the fine root system are relevant to calculations of the carbon
      balance of the ecosystem, and there is also a need to quantify changes in this
      component caused by disturbances. Mediterranean forest systems have historically
      been coppiced to obtain charcoal. As a result of the resprouting capacity of holm
      oaks (Quercus ilex L.), these forests present more than 50% of their biomass
      below ground (stump + roots > 1 cm in diameter), but the effects of thinning on
      the fine root system are unknown. Fine root biomass, production, mortality and
      longevity were studied in a control and a thinned Mediterranean holm oak forest
      by minirhizotron methodology. Observations of fine roots started 2 years after
      thinning and continued for almost 3 years. Extraction of 80% of the former basal
      area of the forest greatly affected carbon allocation patterns. Biomass increased
      by more than 100%, production increased by 76%, mortality increased by 32% and
      longevity decreased by around 2 weeks. The greatest differences between
      treatments were associated with differences in growth during autumn months in the
      top 40 cm of soil, particularly between 10 and 20 cm depth.

PMID- 14597432
TI  - Laparoscopic adrenalectomy: there can be no doubt.

PMID- 14597433
TI  - Freezing breast cancers to enhance complete resection.

PMID- 14597434
TI  - A change in paradigm of breast cancer treatment--not technique--for nodal
      staging.

PMID- 14597435
TI  - Radiofrequency ablation of hepatic malignancies: inexpensive and minimally
      invasive but should it replace resection?

PMID- 14597436
TI  - The staging of gastric cancer: nothing novel but perhaps better.

PMID- 14597437
TI  - The significance of hepatic pedicle lymph nodes metastases in surgical management
      of colorectal liver metastases and of other liver malignancies.
AB  - BACKGROUND: Surgical resection of colorectal liver metastases (CLM) is the only
      hope for cure, with a 5-year survival rate ranging from 20% to 54%. However, the
      resectability rate of CLM is reported to be <20%. This limitation is mainly due
      to insufficient remnant liver and to extrahepatic disease. Among extrahepatic
      locations, lymph node metastases are often considered indications of a very poor
      prognosis and a contra-indication to resection. METHODS: and RESULTS: Our studies
      showed that the prevalence of hepatic pedicle lymph node metastases ranges from
      10% to 20%. When located near the hilum and along the hepatic pedicle (area 1)
      they should not be considered an absolute contra-indication to resection of CLM,
      and an extended lymphadenectomy should be performed. However, when they reach the
      celiac trunk (area 2), there is no survival benefit after resection of CLM. For
      other cases of liver malignancies, lymph node dissection seems justified only in
      cases of fibrolamellar hepatocellular carcinoma and in case of hilar
      cholangiocarcinoma. However, few data are available, and they are controversial.
      CONCLUSIONS: There is a need for more evaluation of lymph node involvement, at
      least in patients with high risk of such an extension, i.e., patients with more
      than three metastases, located in segment 4 or 5. There is also a need for
      prospective trials in order to evaluate the survival benefit of liver resection
      in such circumstances and the impact of extensive lymphadenectomy.

PMID- 14597438
TI  - One hundred laparoscopic adrenalectomies: a single surgeon's experience.
AB  - BACKGROUND: Since the first laparoscopic adrenalectomy was performed in 1992, it
      has quickly gained acceptance as the standard of care for the treatment of benign
      adrenal neoplasms. We report a single surgeon's experience with 100 consecutive
      laparoscopic adrenalectomies. METHODS: The records of all patients having
      adrenalectomy at the Johns Hopkins Hospital from 1993 until 2000 were reviewed.
      We examined the length of stay, time to diet resumption, perioperative morbidity,
      operative cost, and total cost of 100 consecutive laparoscopic adrenalectomies.
      These data are compared with those of 20 patients within our institution having
      open adrenalectomy and with 428 patients statewide having all forms of
      adrenalectomy during the same time period. RESULTS: A total of 93 patients had
      unilateral laparoscopic adrenalectomy and 7 had bilateral procedures. The mean
      age was 49 years (11 to 70). Indications were aldosteronoma (n = 40),
      pheochromocytoma (n = 22), glucocorticoid-producing adenoma (n = 14),
      nonfunctioning adenoma (n = 12) Cushing's disease (n = 5), and others (n = 7).
      The median length of stay for this series was 1.0 day. Average length of stay and
      time to resumption of diet were 1.8 and 1.0 days, respectively. Patients having
      open procedures during this same time period had an average length of stay of 6.5
      days. CONCLUSIONS: Laparoscopic adrenalectomy provides clear advantages over open
      adrenalectomy. Patients having laparoscopic adrenalectomy have decreased length
      of stay, shorter time to resumption of diet, and lower total hospital charges
      when compared with those having open adrenalectomy.

PMID- 14597439
TI  - Pilot trial of cryoprobe-assisted breast-conserving surgery for small ultrasound
      visible cancers.
AB  - BACKGROUND: Stereotactic and ultrasonography-guided large core needle biopsy has
      replaced wire localization biopsy as the diagnostic method of choice. Lumpectomy
      alternatives are being sought to eliminate the need for preoperative wire
      localization, to facilitate easier and more accurate resection, and to decrease
      positive margin rates. Cryoprobe-assisted lumpectomy (CAL) was investigated as an
      alternative. METHODS: Patients with ultrasonographically visible breast cancers
      that otherwise would have required wire localization participated. Before
      lumpectomy, a cryoprobe (Visica; Sanarus, Pleasanton, CA) was inserted through a
      3-mm skin incision and directed by ultrasonography through the center of the
      tumor. An ice ball was created that enveloped the tumor plus an adjacent 5-10 mm
      of sonographically normal breast tissue. RESULTS: Twenty-four CAL procedures were
      performed and all lesions were successfully localized. Mean (+/-SD) tumor size
      was 1.2 +/-.4 cm (range,.7-2.0 cm). Mean dimensions of the ice ball before
      excision were 3.9 +/-.3 cm by 2.5 +/-.5 cm, and the ice margin around the tumor
      was 8 +/- 2 mm. The size of the ice ball was controlled to the millimeter, and
      the ice ball itself provided a precise template around which to dissect. The
      margin re-excision rate was 5.6% among patients with an ice margin greater than 6
      mm. CONCLUSIONS: CAL is a superior alternative to wire localization.
      Ultrasonographic visualization of the ice ball allows the size of the margin and
      tissue resected to be individually tailored and accurate within millimeters. The
      created template allows a precise lumpectomy, adding a dimension of control not
      previously realized with any other technology.

PMID- 14597440
TI  - Impact of clinicopathological factors on sensitivity of axillary ultrasonography
      in the detection of axillary nodal metastases in patients with breast cancer.
AB  - BACKGROUND: Ultrasonography and fine-needle aspiration (FNA) are used to evaluate
      the breast and regional nodes in breast cancer patients. We sought to identify
      factors influencing the sensitivity of ultrasonography for detection of nodal
      metastasis. METHODS: Patients with a clinically negative axilla who underwent
      axillary ultrasonography and sentinel lymph node biopsy were included. RESULTS:
      Of 208 patients, axillary ultrasonography was negative in 180 (86%) and
      suspicious or indeterminate in 28 (14%). FNA was performed in 22 patients whose
      findings were indeterminate or suspicious, and 3 were positive for malignancy.
      Final pathological examinations revealed positive nodes in 53 patients: 39 (22%)
      of 180 with negative ultrasonographic findings and 14 (50%) of 28 with
      indeterminate or suspicious ultrasonographic findings (P =.001). Excisional
      biopsy was more common for patients with indeterminate or suspicious findings on
      preoperative ultrasonography (P =.038). There were no significant differences in
      tumor size, histological features, size of nodal metastasis, or number of
      positive nodes between patients whose ultrasonography findings were negative and
      those whose findings were indeterminate or suspicious. CONCLUSIONS:
      Ultrasonographically suggested nodal metastasis is associated with the finding of
      nodal disease on final pathological examination. No significant clinicopathologic
      criteria were found to impact sensitivity of ultrasonography; however, excisional
      biopsy for diagnosis may be a confounding variable in subsequent axillary
      ultrasonography.

PMID- 14597441
TI  - Breast cancer in women with recent exposure to fertility medications is
      associated with poor prognostic features.
AB  - BACKGROUND: Fertility drug therapy (FDT) induces supraphysiologic endogenous
      estrogen production and might transiently increase breast cancer risk. Tumors
      developing following FDT exposure have not been extensively studied. METHODS:
      Thirty-eight breast cancer patients with 40 primary tumors and with history of
      FDT exposure were identified and compared with two other breast cancer groups:
      women with pregnancy-associated breast cancer (PABC, 22 patients with 23 tumors)
      and premenopausal women born during same calendar years and not exposed to
      hormonal manipulations or recent pregnancy (controls, 192 patients with 201
      tumors). Patients were diagnosed and treated mostly during the last decade.
      RESULTS: Compared with controls, tumors of patients with FDT exposure presented
      at advanced stages (P <.005), were more likely to be estrogen or progesterone
      receptor negative (P <.03) and of poor histology grade (P <.0002). Aggressive
      features predominated among women diagnosed within 2 years of an FDT cycle (P
      <.05). FDT and PABC groups shared similarities. With a median follow-up of 43
      months, relapse-free and cancer-free survival rates were significantly reduced in
      the FDT and PABC groups (P <.01 and P <.01, respectively). Multivariate analysis
      revealed only treatment-defined tumor stage (operable, locally advanced, or
      metastatic) as predictive of survival (P <.0001). CONCLUSION: Breast tumors in
      women with recent FDT exposure present with poor prognostic features and share
      similarities with PABC. Survival is stage dependent.

PMID- 14597442
TI  - Radioactive seed localization breast biopsy and lumpectomy: can specimen
      radiographs be eliminated?
AB  - BACKGROUND: Wire localization (WL) is the current standard for surgical diagnosis
      of nonpalpable breast lesions. Many disadvantages inherent to WL are solved with
      radioactive seed localization (RSL). This trial investigated the ability of RSL
      to reduce the need for specimen radiographs and operating room delays associated
      with WL. METHODS: A total of 134 women were entered onto an institutional review
      board-approved study. RSL was performed by placing a titanium seed containing.29
      to 20 mCi of iodine-125 to within 1 cm of the suggestive breast lesion. The
      surgeon used a handheld gamma detector to locate and excise the iodine-125 seed
      and the lesion. RESULTS: Specimen radiographs were eliminated in 98 (79%) of 124
      patients. Surgical seed retrieval was 100% in 124 patients. No seed migration
      occurred after correct radiographical placement. A total of 26 (21%) of 124
      patients required a specimen radiograph; 22 (85%) of these 26 were performed for
      microcalcifications. CONCLUSIONS: After surgical removal, RSL can eliminate
      specimen radiographs when the radiologist accurately places the seed and the
      pathologist grossly identifies the lesion. If small microcalcifications are noted
      before surgery, then specimen radiographs may be necessary. RSL reduced
      requirements for specimen radiographs, decreased OR time, improved incision
      placement, and improved resections to clear margins.

PMID- 14597443
TI  - Magnetic resonance imaging detects unsuspected disease in patients with invasive
      lobular cancer.
AB  - BACKGROUND: Predicting the extent of disease in the breasts of patients with
      invasive lobular cancer (ILC) can be difficult because of the limits of physical
      examination and standard imaging. We determined the utility of magnetic resonance
      imaging (MRI) in finding otherwise unsuspected cancer in the ipsilateral or
      contralateral breast of patients with ILC. METHODS: Through database review of
      all breast MRIs performed between January 1, 1999, and December 30, 2002, we
      identified patients with newly diagnosed ILC who underwent an MRI for extent-of
      disease evaluation or contralateral screening. MRI findings separate from the
      primary tumor were biopsied and correlated with pathology by using MRI-guided
      biopsy. RESULTS: Sixty-two patients were identified. In all, 59 ipsilateral and
      57 contralateral studies were performed. Suspicious lesions separate from the
      primary tumor were found by MRI in 38 (61%) of 62 patients. Eight patients were
      excluded from further analysis (seven elected mastectomy without biopsy; one had
      an unguided excision). Nineteen of 51 patients with an ipsilateral finding
      underwent MRI-guided biopsy, which revealed cancer in 11, or 22% of those imaged.
      Twenty of 53 patients with a contralateral finding underwent MRI-guided biopsy,
      which revealed cancer in 5, or 9% of those imaged. CONCLUSIONS: MRI of the breast
      identifies unsuspected multicentric or contralateral cancer in patients with ILC.
      These findings support the use of MRI in selected patients with ILC, particularly
      in the ipsilateral breast.

PMID- 14597444
TI  - Outcomes after localized axillary node recurrence in breast cancer.
AB  - BACKGROUND: Localized axillary recurrence (LAR) is an uncommon event. It is
      estimated to occur in 0.5% to 3% of patients when adequate axillary surgery has
      been performed. Although relatively sparse data exist on the outcome of patients
      with LAR, in the era of sentinel node biopsy (SNB) these data may have increased
      relevance. This study assesses the survival outcomes in these patients. METHODS:
      A retrospective chart review was completed. Patient age, tumor size, pathology,
      receptor status, and treatment of the primary breast carcinoma were reviewed.
      Axillary recurrence, treatment, and overall survival data were collected.
      RESULTS: Fifteen patients were identified with LAR that developed at a median of
      77 months after their initial dissection. At the time of treatment for their LAR,
      all patients had completion axillary clearance and six also had a concurrent
      completion mastectomy. Further adjuvant treatment was individualized. Five
      patients (33%) have died, including all patients (3) who developed a LAR within 2
      years of their initial breast cancer presentation. Ten-year overall survival is
      56%. CONCLUSION: Our experience suggests early (<24 months) LAR is indicative of
      a poor prognosis. With multimodal treatment, ten-year overall survival is 56%.

PMID- 14597445
TI  - Combined resection and radiofrequency ablation for advanced hepatic malignancies:
      results in 172 patients.
AB  - BACKGROUND: Resection combined with radiofrequency ablation (RFA) is a novel
      approach in patients who are otherwise unresectable. The objective of this study
      was to investigate the safety and efficacy of hepatic resection combined with
      RFA. METHODS: Patients with multifocal hepatic malignancies were treated with
      surgical resection combined with RFA. All patients were followed prospectively to
      assess complications, treatment response, and recurrence. RESULTS: Seven hundred
      thirty seven tumors in 172 patients were treated (124 with colorectal metastases;
      48 with noncolorectal metastases). RFA was used to treat 350 tumors. Combined
      modality treatment was well tolerated with low operative times and minimal blood
      loss. The postoperative complication rate was 19.8% with a mortality rate of
      2.3%. At a median follow-up of 21.3 months, tumors had recurred in 98 patients
      (56.9%). Failure at the RFA site was uncommon (2.3%). A combined total number of
      tumors treated with resection and RFA >10 was associated with a faster time to
      recurrence (P =.02). The median actuarial survival time was 45.5 months. Patients
      with noncolorectal metastases and those with less operative blood loss had an
      improved survival (P =.03 and P =.04, respectively), whereas radiofrequency
      ablating a lesion >3 cm adversely impacted survival (HR = 1.85, P =.04).
      CONCLUSIONS: Resection combined with RFA provides a surgical option to a group of
      patients with liver metastases who traditionally are unresectable, and may
      increase long-term survival.

PMID- 14597447
TI  - Ratio between metastatic and examined lymph nodes is an independent prognostic
      factor after D2 resection for gastric cancer: analysis of a large European
      monoinstitutional experience.
AB  - BACKGROUND: In view of the lack of consensus on the level and number of lymph
      nodes to be examined for accurate staging of patients with gastric cancer, our
      aim was to evaluate the prognostic significance of lymph node status in a large
      European monoinstitutional experience. METHODS: A review was made of our
      prospective database from 1980 to 2000, when 314 of 445 patients operated for
      gastric adenocarcinoma underwent radical resection (R0) with D2 lymphadenectomy.
      Survival was determined by the Kaplan-Meier method and differences were assessed
      by the log-rank test. Multivariate analysis was performed using the Cox
      proportional hazards model in forward stepwise regression. RESULTS: In 277
      evaluable patients, 5-year survival was 57% (median follow-up, 48 months; range,
      2-251). A total of 7668 lymph nodes were examined (median, 27; range, 11-62). The
      5-year survivals according to the metastatic/examined lymph nodes ratio (N ratio)
      were 14%, 50%, 61%, and 82% in the group of patients with N ratio >25%, 11%-25%,
      1%-10%, and 0%, respectively (P <.0001). At multivariate analysis, the N ratio
      was the best single independent prognostic factor (P =.000). CONCLUSIONS: After
      R0 resection for gastric cancer, the N ratio is a potent prognostic factor. It
      should therefore be considered in the clinical decision making process.

PMID- 14597446
TI  - Hepatic resection and prognosis for patients with hepatocellular carcinoma larger
      than 10 cm: two decades of experience at Chang Gung memorial hospital.
AB  - BACKGROUND: Although screening programs in high-risk populations have facilitated
      the detection of small hepatocellular carcinoma (HCC), some HCC patients continue
      to present with advanced, large tumors. However, reports of hepatic resection for
      HCC larger than 10 cm (L-HCC) are limited. This study aims to determine the
      clinicopathologic factors that influence the prognosis of hepatic resection for L
      HCC. METHODS: The clinical features of 211 L-HCC patients undergoing hepatic
      resection were reviewed. Clinical features and factors influencing the outcome of
      985 patients with HCC smaller than 10 cm (S-HCC) were used for comparison.
      RESULTS: Of 1196 surgically resected HCCs, 211 (17.6%) were L-HCC. Multivariate
      logistic regression analysis showed that the presence of dull abdominal pain, a
      low indocyanine green retention rate value, a high percentage of alfa fetoprotein
      (AFP) >400 ng/mL, major hepatectomy, absence of tumor capsule formation,
      satellite lesions, and vascular invasion were the seven main independent factors
      differentiating L-HCC from S-HCC patients. Significantly worse overall survival
      was noted in L-HCC patients, especially those with tumor rupture, satellite
      lesions, AFP >400 ng/mL, and blood loss of >1 L during surgery. CONCLUSIONS:
      Hepatic resection, when feasible, is safe and is the preferred treatment for L
      HCC patients. However, overall and disease-free survival for L-HCC are worse than
      for S-HCC. Disease-free survival for L-HCC patients undergoing hepatic resection
      is significantly influenced by a high value of alkaline phosphatase and by AFP.
      Overall survival for L-HCC patients undergoing hepatic resection is significantly
      influenced by a high value of AFP, blood loss, tumor rupture, and satellite
      lesions.

PMID- 14597448
TI  - Loss of heterozygosity and DNA aneuploidy in colorectal adenocarcinoma.
AB  - BACKGROUND: This study evaluated the relationship between DNA aneuploidy and loss
      of heterozygosity (LOH) at different genetic loci in colorectal adenocarcinoma.
      METHODS: A total of 112 patients with surgically removed colorectal
      adenocarcinoma in Taipei Veterans General Hospital from January 1999 to July 2001
      were included in this study. The pattern of DNA ploidy was determined with DNA
      flow cytometry, and the LOH of various genetic loci was determined with
      fluorescence polymerase chain reaction and denaturing gradient gel
      electrophoresis. The relationship between DNA ploidy, LOH of various genetic
      loci, and clinicopathologic variables was analyzed with the chi(2) test with
      Yates' correction as well as by multivariate binary logistic regression analysis.
      RESULTS: Seventy-one (63.4%) of the 112 carcinomas had DNA aneuploidy. The DNA
      aneuploidy was not associated with any clinicopathologic variable. Ninety-one
      tumors (81.3%) exhibited LOH in at least one genetic locus. In the univariate
      analysis, the DNA aneuploidy was associated with LOH of Tp53-penta, D8S254,
      D5S346, and high-frequency LOH (P =.001, P =.016, P =.041, and P <.001,
      respectively). In the multivariate analysis, the most significant factor
      influencing DNA aneuploidy was D8S254, followed by Tp53-penta, high-frequency
      LOH, and D5S346. CONCLUSIONS: DNA aneuploidy is strongly associated with LOH at
      specific genetic loci.

PMID- 14597449
TI  - Identifying a region of interest in site- and stage-specific colon cancer on
      chromosome 13.
AB  - BACKGROUND: The role of genes on chromosome 13q has not been confirmed in
      colorectal tumors, in part because most series that have been studied are
      heterogeneous in terms of tumor site, stage, and replication error (RER) status.
      Using a highly homogenous series of colon tumors, our aim was to identify areas
      of interest on 13q that are important in carcinogenesis. METHODS: Twenty-three
      RER-negative tumor specimens from patients with right-sided Dukes' stage C colon
      tumors were selected for analysis with 10 microsatellite markers spanning 13q.
      The polymerase chain reaction-amplified products were analyzed by using a
      standard fluorescent loss of heterozygosity/allele imbalance assay. RESULTS:
      Markers showing the highest frequency of allelic imbalance were as follows:
      D13S175 (31%), D13S289 (27%), D13S263 (25%), and D13S265 (27%). The overall
      resolution of the map was approximately 11.4 to 11.7 cM. CONCLUSIONS: This study
      of right-sided, RER-negative, Dukes' stage C colon tumors showed the highest area
      of allelic imbalance corresponding to 13q11.2-11. This region includes LATS2
      (large tumor suppressor 2 gene) and FGF9 (fibroblast growth factor 9), which may
      be involved in carcinogenesis.

PMID- 14597450
TI  - Pitfalls of positive findings in staging esophageal cancer with F-18
      fluorodeoxyglucose positron emission tomography.
AB  - BACKGROUND: 18-F-fluorodeoxyglucose positron emission tomography (FDG-PET) is
      valuable in staging of esophageal cancer. However, FDG-PET may falsely upstage
      patients leading to incorrect exclusion from surgical treatment. This study was
      performed to determine the false-positive rate and possible causes. METHODS: The
      rate of false-positive lesions on FDG-PET was documented in 86 out of a group of
      98 patients. Lesions were defined as false positive when pathological examination
      was negative or as absence of tumor activity within 6 months of follow-up. To
      evaluate the influence of a learning curve on the false-positive rate, the PET
      scans were revised recently. RESULTS: False-positive lesions were found in 13
      patients (13 of 86; 15%). FDG-PET incorrectly revealed only locoregional node
      metastases in 5 patients in whom surgery with curative intent was performed. Ten
      lesions in the other 8 patients were classified as distant organ or as
      nonregional node metastases (M1a/1b). Finally, 5 patients upstaged to M1a/1b
      underwent a curative resection. The number of false-positive lesions decreased
      from 16 to 5 (6%) after revision. CONCLUSIONS: Proper interpretation of FDG-PET
      in staging esophageal cancer is impeded by false-positive results. Even after
      completion of the learning curve, positive FDG-PET findings still have to be
      confirmed by additional investigations.

PMID- 14597452
TI  - Workload projections for surgical oncology: will we need more surgeons?
AB  - BACKGROUND: Over the next two decades, the US population will experience dramatic
      growth in the number and relative proportion of older individuals. The aim of
      this study was to quantify the effect of these changes on the demand for
      oncological procedures. METHODS: The 2000 Nationwide Inpatient Sample and the
      1996 National Survey of Ambulatory Surgery were used to compute age-specific
      incidence rates for oncological procedures of the breast, colon, rectum, stomach,
      pancreas, and esophagus. Procedure rates were combined with census projections
      for 2010 and 2020 to estimate the future utilization of each procedure. RESULTS:
      By 2020, the number of patients undergoing oncological procedures is projected to
      increase by 24% to 51%. The bulk of growth in procedures is derived from
      outpatient procedures, but significant growth will also be seen in inpatient
      procedures. CONCLUSIONS: The aging of the population will generate an enormous
      growth in demand for oncological procedures. If a shortage of surgeons performing
      these procedures does occur, the result will inevitably be decreased access to
      care. To prevent this from happening, the ability of surgeons to cope with an
      increased burden of work needs to be critically evaluated and improved.

PMID- 14597451
TI  - Transanal endoscopic microsurgery: a viable operative alternative in selected
      patients with rectal lesions.
AB  - BACKGROUND: Local excision of rectal lesions is being increasingly undertaken,
      especially in those unfit for major surgery. The traditional transanal approach
      is often cumbersome and limited to low and mid rectal lesions. Transanal
      endoscopic microsurgery (TEMS) is being used to excise both benign and malignant
      rectal lesions, including those in the upper rectum. METHODS: Prospective
      analysis of all patients undergoing a TEMS excision between January 1997 and
      December 2000 in a specialized colorectal unit. RESULTS: Forty patients underwent
      a TEMS resection, with a mean age of 72 years (SD, 10 years). The mean distance
      of the lesions from the anal verge was 9.8 cm (SD, 3.1 cm). In 24 patients, the
      lesion was located >or=10 cm from the anal verge, making them unsuitable for
      traditional transanal resection. The mean operative time was 91 minutes (SD, 34
      minutes), and the mean postoperative stay was 3 days (SD, 1.5 days). No mortality
      was associated with the procedure, and there was minimal morbidity in 15%. There
      has been no recurrence in the 18 patients who had a malignant lesion excised.
      CONCLUSIONS: The TEMS operating system provides the surgeon with a suitable
      alternative for the resection of benign and malignant rectal neoplasms in
      selected patients. It has the advantage of providing visual clarity of the
      operative field, allowing more precise dissection and a minimally invasive
      approach to mid and upper rectal lesions. There has been no mortality and minimal
      morbidity. We advocate its inclusion as part of a colorectal surgeon's operative
      armamentarium for these selected cases.

PMID- 14597453
TI  - Dermatofibrosarcoma protuberans: reappraisal of wide local excision and impact of
      inadequate initial treatment.
AB  - BACKGROUND: The extent of local invasion in dermatofibrosarcoma protuberans
      (DFSP) is often clinically difficult to appreciate, and this leads to inadequate
      resections. We examined the effect of inadequate initial treatment and the
      efficacy of wide resection. METHODS: We performed a retrospective analysis of the
      records of 35 patients with DFSP treated at our institution (1985 and 2001). Data
      were analyzed with Wilcoxon's ranked sum test and Fisher's exact test. RESULTS:
      Of the 24 patients eligible for analysis, 11 had definitive wide resection after
      diagnostic excisions elsewhere (primary group), and 13 had recurrent tumors after
      previous surgical treatment elsewhere (recurrent group). Twenty-three patients
      were treated with wide resection only, and adjuvant radiation was administered to
      one patient who had a fibrosarcoma. At a median follow-up of 54 months, patients
      definitively treated at our institution had a 100% local recurrence-free
      survival. In comparison to the primary group, recurrent DFSPs were significantly
      larger and deeper and occurred in the head and neck region. Five cases had bone
      involvement, and of these, 80% occurred in the recurrent group. CONCLUSIONS:
      Inadequate initial treatment results in larger, deeper recurrent lesions, but
      these can be managed by appropriate wide excision. Wide resection of DFSP
      (whether recurrent or primary) with negative histological margins predicts a
      superior local recurrence-free survival.

PMID- 14597454
TI  - Prognostic value of plasma and serum VEGF levels in patients with resectable
      hepatocellular carcinoma.

PMID- 14597455
TI  - Outcomes and prognostic factors in 267 patients with severe acute respiratory
      syndrome in Hong Kong.
AB  - BACKGROUND: Severe acute respiratory syndrome (SARS) has become a global public
      health emergency. OBJECTIVE: To evaluate the characteristics and outcomes of
      patients with SARS in Hong Kong and to identify predictors of mortality. DESIGN:
      Retrospective cohort study. SETTING: Quarantine hospital for patients with SARS
      in Hong Kong. PATIENTS: 267 consecutive patients hospitalized from 26 February to
      31 March 2003 for probable or confirmed SARS. MEASUREMENTS: Clinical, laboratory,
      and radiographic measures; 3-month mortality rate. RESULTS: According to our case
      definition, there were 227 cases of confirmed SARS and 40 cases of probable SARS.
      Common presenting symptoms were fever (99% of patients), chills (74%), malaise
      (63%), and myalgia (50%). Laboratory findings included lymphopenia (73%),
      thrombocytopenia (50%), hyponatremia (60%), and elevated levels of lactate
      dehydrogenase (47%) and C-reactive protein (75%). During hospitalization,
      incidence of diarrhea (53%), anemia (53%), and acute renal failure (6%)
      increased. Sixty-nine patients (26%) required intensive care because of
      respiratory failure. The 3-month mortality rate was 12% (95% CI, 8% to 16%).
      Factors contributing to mortality were respiratory failure, acute renal failure,
      and nosocomial sepsis. On multivariate Cox regression, age older than 60 years
      (relative risk, 5.10 [CI, 2.30 to 11.31]; P < 0.001) and lactate dehydrogenase
      level greater than 3.8 micro kat/L at presentation (relative risk, 2.20 [CI, 1.03
      to 4.71]; P = 0.04) were independent predictors of mortality. CONCLUSION: Because
      of the longer follow-up period in our cohort, the mortality rate in these
      patients is higher than rates reported in previous studies. Advanced age and high
      lactate dehydrogenase level at presentation predict mortality. *For members of
      the Princess Margaret Hospital SARS Study Group, see the Appendix.

PMID- 14597456
TI  - Effectiveness of leech therapy in osteoarthritis of the knee: a randomized,
      controlled trial.
AB  - BACKGROUND: Leech therapy was commonly used in traditional medicine for treating
      localized pain. Clinically significant pain relief after leech therapy for
      osteoarthritis of the knee has been demonstrated by preliminary data. OBJECTIVE:
      To evaluate the effectiveness of leech therapy for symptomatic relief of
      osteoarthritis of the knee. DESIGN: Randomized, controlled trial. SETTING:
      Outpatient department for integrative medicine of an academic teaching hospital.
      PATIENTS: 51 patients with osteoarthritis of the knee (leech therapy: 24
      patients, mean age [+/-SD], 62.5 +/- 10.2 years; topical diclofenac therapy: 27
      patients, mean age [+/-SD], 65.5 +/- 6.7 years). INTERVENTION: A single treatment
      with 4 to 6 locally applied leeches (leech therapy group) or a 28-day topical
      diclofenac regimen (control group). MEASUREMENTS: Mean of the pain, function, and
      stiffness subscores of the Western Ontario and McMaster Universities
      Osteoarthritis Index and physical sum score of the Medical Outcomes Study 36-Item
      Short-Form Health Survey with group comparisons at days 3, 7, 28, and 91.
      RESULTS: The primary end point, pain at day 7, was reduced from a mean (+/-SD) of
      53.5 +/- 13.7 to 19.3 +/- 12.2 after leech therapy compared with 51.5 +/- 16.8 to
      42.4 +/- 19.7 with topical diclofenac (estimated group difference, -23.9 [95% CI,
      -32.8 to -15.1]; P < 0.001). Although the difference between group pain scores
      was no longer significant after day 7, differences for function, stiffness, and
      total symptoms remained significant in favor of leech therapy until the end of
      study and for quality of life until day 28. Results were not affected by outcome
      expectation. CONCLUSIONS: Leech therapy helps relieve symptoms in patients with
      osteoarthritis of the knee. The potential of leech therapy for treating
      osteoarthritis and the pharmacologic properties of leech saliva remain to be
      clarified.

PMID- 14597457
TI  - Systolic blood pressure, diastolic blood pressure, and pulse pressure: an
      evaluation of their joint effect on mortality.
AB  - BACKGROUND: The relative importance of blood pressure components (systolic blood
      pressure, diastolic blood pressure, and pulse pressure) on cardiovascular risk is
      currently being debated. Many studies, however, are limited by inadequate
      statistical methods to separate these effects. OBJECTIVE: To evaluate the joint
      effect of blood pressure components on all-cause and cardiovascular mortality by
      using nonparametric and change point models. DESIGN: Prospective cohort study.
      SETTING: 15-year mortality follow-up of participants in the Second National
      Health and Nutrition Examination Survey. PARTICIPANTS: 7830 white and African
      American men and women 30 to 74 years of age, apparently free of cardiovascular
      disease at baseline. MEASUREMENTS: Baseline blood pressure, corrected for
      measurement error. RESULTS: Of the 1588 patients who died, 582 died of
      cardiovascular disease. Systolic blood pressure was linearly related to all-cause
      and cardiovascular mortality in younger and elderly participants. The association
      of diastolic blood pressure with all-cause and cardiovascular mortality was
      hockey stick-shaped (flat then increasing) in younger participants and J-shaped
      in elderly participants. Increased pulse pressure was associated with increased
      risk, decreased risk, or no change in risk depending on age and systolic and
      diastolic blood pressure. CONCLUSIONS: On the basis of these and previous data,
      the evidence for a monotonic association of systolic blood pressure with all
      cause and cardiovascular mortality is compelling, but a J-shaped association for
      diastolic blood pressure may develop at older age. The complexity of the
      association of pulse pressure with mortality discourages its use for prognostic
      or therapeutic decisions.

PMID- 14597458
TI  - The quality of medical care provided to vulnerable community-dwelling older
      patients.
AB  - BACKGROUND: Many people 65 years of age and older are at risk for functional
      decline and death. However, the resource-intensive medical care provided to this
      group has received little evaluation. Previous studies have focused on general
      medical conditions aimed at prolonging life, not on geriatric issues important
      for quality of life. OBJECTIVE: To measure the quality of medical care provided
      to vulnerable elders by evaluating the process of care using Assessing Care of
      Vulnerable Elders quality indicators (QIs). DESIGN: Observational cohort study.
      SETTING: Managed care organizations in the northeastern and southwestern United
      States. PATIENTS: Vulnerable older patients identified by a brief interview from
      a random sample of community-dwelling adults 65 years of age or older who were
      enrolled in 2 managed care organizations and received care between July 1998 and
      July 1999. MEASUREMENTS: Percentage of 207 QIs passed, overall and for 22 target
      conditions; by domain of care (prevention, diagnosis, treatment, and follow-up);
      and by general medical condition (for example, diabetes and heart failure) or
      geriatric condition (for example, falls and incontinence). RESULTS: Patients were
      eligible for 10 711 QIs, of which 55% were passed. There was no overall
      difference between managed care organizations. Wide variation in adherence was
      found among conditions, ranging from 9% for end-of-life care to 82% for stroke
      care. More treatment QIs were completed (81%) compared with other domains (follow
      up, 63%; diagnosis, 46%; and prevention, 43%). Adherence to QIs was lower for
      geriatric conditions than for general medical conditions (31% vs. 52%; P <
      0.001). CONCLUSIONS: Care for vulnerable elders falls short of acceptable levels
      for a wide variety of conditions. Care for geriatric conditions is much less
      optimal than care for general medical conditions.

PMID- 14597459
TI  - Update in critical care.

PMID- 14597460
TI  - Transcatheter closure versus medical therapy of patent foramen ovale and presumed
      paradoxical thromboemboli: a systematic review.
AB  - BACKGROUND: The optimal strategy to prevent recurrent presumed paradoxical emboli
      in patients with patent foramen ovale is unknown. PURPOSE: To synthesize the
      current knowledge about and qualitatively assess the relative benefits of
      transcatheter closure versus medical therapy for patent foramen ovale. DATA
      SOURCES: English-language and foreign-language journals listed in the MEDLINE
      database from January 1985 to July 2003 were systematically searched. Secondary
      sources were also used. STUDY SELECTION: Secondary prevention studies of
      transcatheter closure or medical therapy for patent foramen ovale were required
      to include at least 10 patients followed for more than 1 year and to report
      recurrent neurologic events. DATA EXTRACTION: Data from published studies were
      manually extracted and summarized. DATA SYNTHESIS: Ten studies of transcatheter
      closure (1355 patients) and 6 studies of medical therapy (895 patients) for
      patent foramen ovale were included. Overall, the 1-year rate of recurrent
      neurologic thromboembolism with transcatheter intervention was 0% to 4.9%, and
      the incidence of major and minor complications was 1.5% and 7.9%, respectively.
      Medical management was associated with a 1-year recurrence rate of 3.8% to 12.0%.
      However, limitations resulting from uncontrolled data, nonstandardized
      definitions, vigilance of follow-up, and baseline imbalances preclude definitive
      conclusions about the superiority of a particular approach. General differences
      in study samples included older age, greater proportion of men, and higher
      prevalence of diabetes and smoking among medically treated patients. Patients
      undergoing treatment with a transcatheter device were more likely to have had
      multiple thromboembolic events at baseline. CONCLUSION: Transcatheter closure of
      patent foramen ovale may prevent a substantial proportion of cryptogenic strokes.
      Randomized clinical trials are needed.

PMID- 14597461
TI  - Pathogenesis of hypertension.

PMID- 14597462
TI  - ALLHAT, or the soft science of the secondary end point.
AB  - The recent Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack
      Trial (ALLHAT) showed that the primary end point, coronary heart disease, was
      identical in the chlorthalidone, lisinopril, and amlodipine groups. Yet the major
      conclusion of this trial was that thiazide diuretics are superior in preventing 1
      or more major forms of cardiovascular disease and should be preferred for first
      line antihypertensive therapy. This conclusion was based solely on an analysis of
      secondary end points and cost. As evidenced by the dictum to "use thiazides for
      most patients with uncomplicated hypertension" in the Seventh Report of the Joint
      National Committee on the Prevention, Detection, Evaluation, and Treatment of
      High Blood Pressure, this interpretation of ALLHAT broadly adumbrated these
      guidelines. Although diuretics will rightfully remain a cornerstone in
      antihypertensive therapy, we should remember (as we were told by the ALLHAT
      investigators) that secondary end points are "soft data" that should not form a
      basis for main conclusions or lead to a labeling of a drug class as preferred.

PMID- 14597463
TI  - Multidisciplinary integrative approach to treating knee pain in patients with
      osteoarthritis.

PMID- 14597464
TI  - Establishing benchmarks for quality care for an aging population: caring for
      vulnerable older adults.

PMID- 14597465
TI  - Patent cardiac foramen ovale: stroke risk and closure.

PMID- 14597466
TI  - Tattoo.

PMID- 14597467
TI  - Delayed-onset heparin-induced thrombocytopenia.

PMID- 14597468
TI  - Delayed-onset heparin-induced thrombocytopenia.

PMID- 14597469
TI  - Hope for the best, and prepare for the worst.

PMID- 14597470
TI  - Laboratory monitoring of high-dose factor VIIa therapy.

PMID- 14597471
TI  - Atorvastatin-induced polyneuropathy.

PMID- 14597472
TI  - Summaries for patients. Characteristics and outcomes of patients with severe
      acute respiratory syndrome (SARS) in Hong Kong.

PMID- 14597473
TI  - Summaries for patients. Leeches to treat knee osteoarthritis.

PMID- 14597474
TI  - Summaries for patients. Effects of blood pressure measurements on mortality.

PMID- 14597475
TI  - Summaries for patients. Quality of medical care for patients older than age 65
      years.

PMID- 14597476
TI  - Fungal endocarditis due to Scopulariopsis.

PMID- 14597477
TI  - Providing free care to the uninsured: how much should physicians give?

PMID- 14597478
TI  - Distinct responses of membranoproliferative glomerulonephritis-related
      proteinuria to spironolactone with and without angiotensin II blockade.

PMID- 14597479
TI  - Paradoxical lowering of high-density lipoprotein cholesterol level in 2 patients
      receiving fenofibrate and a thiazolidinedione.

PMID- 14597480
TI  - Effect of phosphodiesterase-5 inhibitor, sildenafil (Viagra), in animal models of
      airways disease.
AB  - Phosphodiesterase (PDE)-5 degrades guanosine 3',5'cyclic monophosphate (cGMP) and
      its inhibitor sildenafil citrate (Viagra) treats erectile dysfunction by smooth
      muscle relaxation through elevated cGMP. Sildenafil was examined in two guinea
      pig models of airways disease: guinea pigs exposed to LPS or sensitized guinea
      pigs with atopy exposed to ovalbumen. Ovalbumen exposure caused early- and late
      phase bronchoconstrictor responses, measured in conscious animals by whole-body
      plethysmography. Twenty-four hours after ovalbumen exposure there was airway
      hyperreactivity (AHR) to inhaled histamine and significantly elevated
      macrophages, eosinophils, and nitric oxide (NO) metabolites in bronchoalveolar
      lavage fluid. Sildenafil treatment (1 mg/kg, intraperitoneally) failed to affect
      the early and late responses but significantly reduced AHR, leukocyte influx, and
      elevated NO. LPS exposure (30 microg/ml) caused AHR to histamine at 1 hour and
      macrophage, eosinophil, and neutrophil influx at 24 hours with raised NO.
      Sildenafil pretreatment inhibited LPS-induced AHR, leukocyte influx, and NO
      generation. The effectiveness of sildenafil was not dependent on endogenous NO
      because inhibition of NO synthase with Nomega-nitro-L-arginine methyl ester did
      not prevent its action. Inhibition of PDE5 by sildenafil was confirmed by
      elevated S-nitroso-N-acetylpenicillamine-induced cGMP generation in isolated
      lungs. These antiinflammatory actions of sildenafil in guinea pig models suggest
      that PDE5 inhibitors may have potential in treating airways disease.

PMID- 14597481
TI  - Free secretory component from cystic fibrosis sputa displays the cystic fibrosis
      glycosylation phenotype.
AB  - Secretory IgA contributes to humoral defense mechanisms against pathogens
      targeting mucosal surfaces, and secretory component (SC) fulfills multiple roles
      in this defense. The aims of this study were to quantify total SC and to analyze
      the form of free SC in sputa from normal subjects, subjects with asthma, and
      subjects with cystic fibrosis (CF). Significantly higher levels of SC were
      detected in CF compared with both other groups. Gel filtration chromatography
      revealed that SC in CF was relatively degraded. Free SC normally binds
      interleukin (IL)-8 and inhibits its function. However, in CF sputa, IL-8 binding
      to intact SC was reduced. Analysis of the total carbohydrate content of free SC
      signified overglycosylation in CF compared with normal subjects and subjects with
      asthma. Monosaccharide composition analysis of free SC from CF subjects revealed
      overfucosylation and undersialylation, in agreement with the reported CF
      glycosylation phenotype. SC binding to IL-8 did not interfere with the binding of
      IL-8 to heparin, indicating distinct binding sites on IL-8 for negative
      regulation of function by SC and heparin. We suggest that defective structure and
      function of SC contribute to the characteristic sustained inflammatory response
      in the CF airways.

PMID- 14597482
TI  - Controlled trial of continuous positive airway pressure in obstructive sleep
      apnea and heart failure.
AB  - Obstructive sleep apnea (OSA) is highly prevalent among patients with congestive
      heart failure (CHF) and may contribute to progression of cardiac dysfunction via
      hypoxia, elevated sympathetic nervous system activity, and systemic hypertension.
      Our aim was to assess the long-term effect of OSA treatment with nocturnal
      continuous positive airway pressure (CPAP) on systolic heart function,
      sympathetic activity, blood pressure, and quality of life in patients with CHF.
      Fifty-five patients with CHF and OSA were randomized to 3 months of CPAP or
      control groups. End points were changes in left ventricular ejection fraction,
      overnight urinary norepinephrine excretion, blood pressure, and quality of life.
      Nineteen patients in the CPAP group and 21 control subjects completed the study.
      Compared with the control group, CPAP treatment was associated with significant
      improvements in left ventricular ejection fraction (delta 1.5 +/- 1.4% vs. 5.0 +/
      1.0%, respectively, p = 0.04), reductions in overnight urinary norepinephrine
      excretion (delta 1.6 +/- 3.7 vs. -9.9 +/- 3.6 nmol/mmol creatinine, p = 0.036),
      and improvements in quality of life. There were no significant changes in
      systemic blood pressure. In conclusion, treatment of OSA among patients with CHF
      leads to improvement in cardiac function, sympathetic activity, and quality of
      life.

PMID- 14597483
TI  - Interrupter resistance and wheezing phenotypes at 4 years of age.
AB  - It is difficult to distinguish young children with respiratory symptoms who will
      develop asthma from those with transient symptoms only. Measurement of
      interrupter resistance may help to identify children at high risk of asthma. The
      aim of this study is to compare interrupter resistance in 4-year-old children
      with different wheezing phenotypes. All children participated in the Prevention
      and Incidence of Asthma and Mite Allergy cohort, a prospective birth cohort of
      more than 4,000 children. At 4 years of age, data on interrupter resistance plus
      wheezing phenotype were available for 838 children. Mean interrupter resistance
      values (95% confidence interval) were 0.95 (0.93, 0.97), 0.95 (0.92, 0.98), 0.96
      (0.87, 1.05), and 1.08 (1.02, 1.14) kPa.L(-1).second for never (n = 482), early
      transient (n = 236), late-onset (n = 22), and persistent (n = 98) wheezing
      phenotypes, respectively. Additional analyses were performed for children with
      atopic and nonatopic mothers separately. Both in children with atopic and
      nonatopic mothers, children with persistent wheeze had significantly higher
      interrupter resistance values than children with never and early wheeze. In
      conclusion, mean interrupter resistance values were higher in children with
      persistent wheeze as compared with children with never and early transient
      wheezing phenotypes.

PMID- 14597484
TI  - Transforming growth factor-beta1 promoter polymorphism C-509T is associated with
      asthma.
AB  - Transforming growth factor-beta1 (TGF-beta1) is increased in the lungs of
      individuals with asthma and may modulate airway inflammation and remodeling. Some
      genetic studies have found that a C-to-T single-nucleotide polymorphism (C-509T)
      in the TGF-beta1 gene promoter may be associated with altered gene expression and
      asthma phenotype. To build on these data, we performed a case-control association
      study at this locus involving 527 subjects with asthma and 170 control subjects
      without asthma. All individuals were white. Genotyping at 49 unlinked
      polymorphisms indicated that a subset of case subjects and all control subjects
      were well matched and without evidence of population stratification. Logistic
      regression was used to model the effects of age, sex, and genotype on case
      control status. The diagnosis of asthma was positively associated with the T
      allele and TT genotype under a codominant model (odds ratio, 2.98; 95% confidence
      interval, 1.45 to 6.25; p = 0.003). Total serum IgE, eosinophil count, and FEV1%
      predicted levels were not associated with this polymorphism. Furthermore, we show
      that the C-509T polymorphism alters TGF-beta1 promoter-reporter activity and
      promoter interactions with the transcription factor Yin Yang 1. We conclude that
      the T allele of C-509T is associated with the diagnosis of asthma and may enhance
      TGF-beta1 gene transcription.

PMID- 14597485
TI  - Continuous exposure to house dust mite elicits chronic airway inflammation and
      structural remodeling.
AB  - It is now fully appreciated that asthma is a disease of a chronic nature
      resulting from intermittent or continued aeroallergen exposure leading to airway
      inflammation. To investigate responses to continuous antigen exposure, mice were
      exposed to either house dust mite extract (HDM) or ovalbumin intranasally for
      five consecutive days, followed by 2 days of rest, for up to seven consecutive
      weeks. Continuous exposure to HDM, unlike ovalbumin, elicited severe and
      persistent eosinophilic airway inflammation. Flow cytometric analysis
      demonstrated an accumulation of CD4+ lymphocytes in the lung with elevated
      expression of inducible costimulator a marker of T cell activation, and of
      T1/ST2, a marker of helper T Type 2 effector cells. We also detected increased
      and sustained production of helper T cell Type 2-associated cytokines by
      splenocytes of HDM-exposed mice on in vitro HDM recall. Histologic analysis of
      the lung showed evidence of airway remodeling in mice exposed to HDM, with goblet
      cell hyperplasia, collagen deposition, and peribronchial accumulation of
      contractile tissue. In addition, HDM-exposed mice demonstrated severe airway
      hyperreactivity to methacholine. Finally, these responses were studied for up to
      9 weeks after cessation of HDM exposure. We observed that whereas airway
      inflammation resolved fully, the remodeling changes did not resolve and airway
      hyperreactivity resolved only partly.

PMID- 14597487
TI  - Training of medical professionals and the delivery of health care as related to
      cultural identity groups.

PMID- 14597486
TI  - Strain-specific immune response to Haemophilus influenzae in chronic obstructive
      pulmonary disease.
AB  - Previous studies of immune response to Haemophilus influenzae after exacerbations
      of chronic obstructive pulmonary disease (COPD) have yielded contradictory
      results. Using homologous (infecting) strains and immunoassays to surface-exposed
      epitopes, we tested the hypothesis that adults with COPD make new antibodies to
      strain-specific, surface-exposed epitopes on H. influenzae after exacerbations.
      We collected clinical information, sputum, and serum monthly and during
      exacerbations from 81 patients with COPD over 56 months. Serum antibodies to H.
      influenzae after exacerbations associated with H. influenzae in sputum were
      detected with whole bacterial cell ELISA and bactericidal assays. An immune
      response to homologous H. influenzae occurred after 22 of 36 (61.1%)
      exacerbations with newly acquired strains compared with 7 of 33 (21.2%)
      exacerbations with preexisting strains (odds ratio [OR] = 4.4; 95%, 1.8 to 10.8;
      p = 0.001). An absence of an immune response was strongly associated with
      complement sensitivity (OR = 0.03; 95% confidence interval, 0.003 to 0.22; p =
      0.001). New bactericidal antibodies developed after exacerbations were highly
      strain specific, showing bactericidal activity for only 11 of 90 (12.2%)
      heterologous strains. Development of an immune response to H. influenzae supports
      its role in causing exacerbations. The strain specificity of the immune response
      likely represents a mechanism of recurrent exacerbations.

PMID- 14597488
TI  - Executive summary: disparities in emergency health care.

PMID- 14597489
TI  - Disparities in health care: an overview.
AB  - The most important predictor of quality of health care across all racial and
      ethnic groups is access, especially insurance status and the ability to pay for
      health care. If we consider populations with equal access to health care, two
      groups emerge with differing qualities of health care: non-minority and minority
      populations. When studies control for the stage of disease at presentation,
      comorbidities, severity of illness, and other variables, substantial differences
      in health care based on race and ethnicity can still be found. Raising the
      consciousness of this issue is an important step toward recognizing and
      eliminating health care disparities.

PMID- 14597490
TI  - Researching disparities: strategies for primary data collection.
AB  - Comparatively little disparities research to date has focused on emergency
      medicine. However, the body of disparities research developed in other areas of
      health care has identified a number of issues that are directly applicable. To
      promote research on disparities in emergency medicine, this article addresses
      several of these issues related to collecting and classifying data on
      race/ethnicity and socioeconomic status and selected methodologic issues that are
      particularly important for evaluating disparities.

PMID- 14597491
TI  - Researching racial and ethnic disparities in emergency medicine.
AB  - The recent Institute of Medicine report "Unequal Treatment: Confronting Racial
      and Ethnic Disparities in Health Care" chronicles a growing body of literature
      describing racial and ethnic disparities in health care delivery. It suggests a
      research agenda designed to better understand and eventually eliminate these
      disparities. Prompted by this report, Academic Emergency Medicine convened a
      Consensus Conference on Disparities in Emergency Health Care on May 28, 2003, in
      Boston. One of the goals of that meeting was to develop a research agenda for
      emergency medicine researchers working on disparities in health care. This report
      describes the results of the consensus conference and suggests such a research
      agenda.

PMID- 14597492
TI  - Health care disparities in emergency medicine.
AB  - The Institute of Medicine's landmark report, "Unequal Treatment: Confronting
      Racial and Ethnic Disparities in Health Care," documents the pervasiveness of
      racial and ethnic disparities in the U.S. health care delivery system, and
      provides several recommendations to address them. It is clear from research data,
      such as those demonstrating racial and ethnic disparities in emergency department
      (ED) pain management, that emergency medicine (EM) is not immune to this problem.
      The IOM authors describe two strategies that can reduce disparities in EM. First,
      workforce diversity is likely to result in a community of emergency physicians
      who are better prepared to understand, learn from, and collaborate with persons
      from other racial, ethnic, and cultural backgrounds, whether these be patients,
      fellow clinicians, or the larger medical and scientific community. Given the
      ethical and practical advantages of a more diverse EM workforce, continued and
      expanded initiatives to increase diversity within EM should be undertaken.
      Second, the specialty's educational programs should produce emergency physicians
      with the skills and knowledge needed to serve an increasingly diverse population.
      This cultural competence should include an awareness of existing racial and
      ethnic health disparities, recognition of the risks of stereotyping and biased
      treatment, and knowledge of the incidence and prevalence of health conditions
      among diverse populations. Culturally competent emergency care providers also
      possess the skills to identify and manage racial and ethnic differences in health
      values, beliefs, and behaviors with the ultimate goal of delivering quality
      health services to all patients cared for in EDs.

PMID- 14597493
TI  - Racial and ethnic disparities in the clinical practice of emergency medicine.
AB  - There is convincing evidence that racial and ethnic disparities exist in the
      provision of health care, including the provision of emergency care; and that
      stereotyping, biases, and uncertainty on the part of health care providers all
      contribute to unequal treatment. Situations, such as the emergency department
      (ED), that are characterized by time pressure, incomplete information, and high
      demands on attention and cognitive resources increase the likelihood that
      stereotypes and bias will affect diagnostic and treatment decisions. It is likely
      that there are many as-yet-undocumented disparities in clinical emergency
      practice. Racial and ethnic disparities may arise in decisions made by out-of
      hospital personnel regarding ambulance destination, triage assessments made by
      nursing personnel, diagnostic testing ordered by physicians or physician
      extenders, and in disposition decisions. The potential for disparate treatment
      includes the timing and intensity of ED therapy as well as patterns of referral,
      prescription choices, and priority for hospital admission and bed assignment. At
      a national roundtable discussion, strategies suggested to address these
      disparities included: increased use of evidence-based clinical guidelines; use of
      continuous quality improvement methods to document individual and institutional
      disparities in performance; zero tolerance for stereotypical remarks in the
      workplace; cultural competence training for emergency providers; increased
      workforce diversity; and increased epidemiologic, clinical, and services
      research. Careful scrutiny of the clinical practice of emergency medicine and
      diligent implementation of strategies to prevent disparities will be required to
      eliminate the individual behaviors and systemic processes that result in the
      delivery of disparate care in EDs.

PMID- 14597494
TI  - Emergency medicine education and health care disparities.
AB  - Education is the means by which learning occurs and, thereby, behavior is
      changed. One means of improving health care disparities is changing the behavior
      and understanding of key personnel in academic health centers. These individuals
      influence policy and procedure, design and evaluate health systems, and define
      curricular standards for graduate and undergraduate medical education. Emergency
      medicine provides many opportunities to educate at all levels, including faculty,
      residents, and students. In addition to our responsibilities in educating
      emergency medicine residents, the emergency department also provides an ideal
      learning environment for medical students and other health care providers. The
      broad issue of disparities in emergency health care may be approached from a
      variety of directions. The Consensus Group on Education chose to focus on
      cultural competency education at several levels as a means of tangibly changing
      its status for both the immediate and long terms.

PMID- 14597495
TI  - Disparities in emergency department health care: systems and administration.
AB  - Disparities are likely to present both in the emergency department and within the
      larger health care system; however, disparities must be recognized to be
      addressed. This article summarizes the proceedings from the AEM Consensus
      Conference 2003: Disparities in Emergency Health Care. The goals of the
      conference were to examine the presence, causes, and outcomes related to
      disparities of health care as they occur in emergency departments, and determine
      the degree to which external forces have an impact on our patients. Participants
      were asked to describe the means of defining, assessing, measuring, and
      investigating disparities that may occur in emergency care. The committee members
      who wrote this report were asked to examine the influence of health care systems
      and administration on disparities in health care, using the following series of
      questions to frame the discussion. 1) Are all disparities bad? 2) Are only the
      vulnerable served inadequately by our current health care system? 3) Are what
      appear to be inequities really systems incompetence? 4) We assume there should be
      no inequality in health care: does society also assume this? 5) What would be the
      systems costs of equality in health care?

PMID- 14597496
TI  - The impact of race on the acute management of chest pain.
AB  - OBJECTIVES: African Americans with acute coronary syndromes receive cardiac
      catheterization less frequently than whites. The objective was to determine if
      such disparities extend to acute evaluation and non interventional treatment.
      METHODS: Data on adults with chest pain (N = 7,935) presenting to eight emergency
      departments (EDs) were evaluated from the Internet Tracking Registry of Acute
      Coronary Syndromes. Groups were selected from final ED diagnosis: 1) acute
      myocardial infarction (AMI), n = 400; 2) unstable angina/non-ST-elevation
      myocardial infarction (UA/NSTEMI), n = 1,153; and 3) nonacute coronary syndrome
      chest pain (non-ACS CP), n = 6,382. American College of Cardiology/American Heart
      Association guidelines for AMI and UA/NSTEMI were used to evaluate racial
      disparities with logistic regression models. Odds ratios (ORs) were adjusted for
      age, gender, guideline publication, and insurance status. Non-ACS CP patients
      were assessed by comparing electrocardiographic (ECG)/laboratory evaluation,
      medical treatment, admission rates, and invasive and noninvasive testing for
      coronary artery disease (CAD). RESULTS: African Americans with UA/NSTEMI received
      glycoprotein IIb/IIIa receptor inhibitors less often than whites (OR, 0.41; 95%
      CI = 0.19 to 0.91). African Americans with non-ACS CP underwent ECG/laboratory
      evaluation, medical treatment, and invasive and noninvasive testing for CAD less
      often than whites (p < 0.05). Other nonwhites with non-ACS CP were admitted and
      received invasive testing for CAD less often than whites (p < 0.01). African
      Americans and other nonwhites with AMI underwent catheterization less frequently
      than whites (OR, 0.45; 95% CI = 0.29 to 0.71 and OR, 0.40; 95% CI = 0.17 to 0.92,
      respectively). A similar disparity in catheterization was noted in UA/NSTEMI
      therapy (OR, 0.53; 95% CI = 0.40 to 0.68 and OR, 0.68; 95% CI = 0.47 to 0.99).
      CONCLUSIONS: Racial disparities in acute chest pain management extend beyond
      cardiac catheterization. Poor compliance with recommended treatments for ACS may
      be an explanation.

PMID- 14597497
TI  - Ethnic and racial disparities in emergency department care for mild traumatic
      brain injury.
AB  - OBJECTIVES: To identify racial, ethnic, and gender disparities in the emergency
      department (ED) care for mild traumatic brain injury (mTBI). METHODS: A secondary
      analysis of ED visits in the National Hospital Ambulatory Medical Care Survey for
      the years 1998 through 2000 was performed. Cases of mTBI were identified using
      ICD-9 codes 800.0, 800.5, 850.9, 801.5, 803.0, 803.5, 804.0, 804.5, 850.0, 850.1,
      850.5, 850.9, 854.0, and 959.01. ED care variables related to imaging,
      procedures, treatments, and disposition were analyzed along racial, ethnic, and
      gender categories. The relationship between race, ethnicity, and selected ED care
      variables was analyzed using multivariate logistic regression with control for
      associated injuries, geographic region, and insurance type. RESULTS: The
      incidence of mTBI was highest among men (590/100,000), Native Americans/Alaska
      Natives (1026.2/100,000), and non-Hispanics (391.1/100,000). After controlling
      for important confounders, Hispanics were more likely than non-Hispanics to
      receive a nasogastric tube (OR, 6.36; 95% CI = 1.2 to 33.6); nonwhites were more
      likely to receive ED care by a resident (OR, 3.09; 95% CI = 1.9 to 5.0) and less
      likely to be sent back to the referring physician after ED discharge (OR, 0.47;
      95% CI = 0.3 to 0.9). Men and women received equivalent ED care. CONCLUSIONS:
      There are significant racial and ethnic but not gender disparities in ED care for
      mTBI. The causes of these disparities and the relationship between these
      disparities and post-mTBI outcome need to be examined.

PMID- 14597498
TI  - Racial and ethnic disparities in pediatric appendicitis rupture rate.
AB  - OBJECTIVES: To determine if there are racial/ethnic differences in the rates of
      appendiceal rupture among the children of two large states. Because rupture is
      primarily due to delayed diagnosis, differences would suggest disparities in
      timely access to quality emergency care. METHODS: This was an observational,
      cross-sectional analysis of full-year samples of acute appendicitis cases from
      California and New York children 4 to 18 years old. Racial/ethnic groups were
      compared for risk of appendiceal rupture adjusted for biological factors both
      before and after adjustment for the following socioeconomic, hospital, and
      admission characteristics: income, insurance, hospital type, and admission
      source. Results were interpreted in light of census data on the proportion of
      immigrants in each racial/ethnic group. RESULTS: Compared with white children
      with acute appendicitis, Hispanic and Asian children have higher odds of rupture
      in California, whereas Asian and black/African American children have higher odds
      in New York. These differences roughly parallel the within-state proportion of
      immigrant children in these groups. Adjustments for family, socioeconomic, and
      hospital characteristics attenuate but do not eliminate disparities. CONCLUSIONS:
      The authors found evidence of significant racial/ethnic disparities in rate of
      appendiceal rupture, an important and preventable outcome, in two large but
      dissimilar states. Immigrant groups may be most at risk for delayed emergency
      care. Future research should focus on immigration and acculturation as risk
      factors for appendicitis rupture in children.

PMID- 14597499
TI  - Is outpatient care associated with lower use of inpatient and emergency care? An
      analysis of persons with HIV disease.
AB  - OBJECTIVES: The authors use data from the AIDS Costs and Service Utilization
      Survey (ACSUS) to investigate the extent to which use of ambulatory medical care
      is associated with inpatient and emergency department use among HIV-infected
      persons. METHODS: Parameter estimates were derived from simultaneous,
      multiequation models. RESULTS: Higher use of ambulatory medical services is not
      significantly associated with lower probability of inpatient admissions or
      emergency department (ED) visits. For the subgroup of patients who received an
      AIDS diagnosis during the study period, however, the number of ambulatory visits
      had significant negative effects on hospitalizations and ED use. CONCLUSIONS:
      Outpatient care may offset inpatient and ED services at particular points in the
      disease course.

PMID- 14597500
TI  - The effect of race/ethnicity and desirable social characteristics on physicians'
      decisions to prescribe opioid analgesics.
AB  - OBJECTIVE: Racial/ethnic disparities in physician treatment have been documented
      in multiple areas, including emergency department (ED) analgesia. The purpose of
      this study was to determine if physicians were predisposed to different treatment
      decisions based on patient race/ethnicity and if physicians' treatment
      predispositions changed when socially desirable information about the patient
      (occupation, socioeconomic status, and relationship with a primary care
      physician) was made explicit. METHODS: The authors developed three clinical
      vignettes designed to engage physicians' decision-making processes. The patient's
      race/ethnicity was included. Each vignette randomly included or omitted explicit
      socially desirable information. The authors mailed 5,750 practicing emergency
      physicians three clinical vignettes and a one-page questionnaire about
      demographic and practice characteristics. Chi-square tests of significance for
      bivariate analyses and multiple logistic regression were used for multivariate
      analyses. RESULTS: A total of 2,872 (53%) of the 5,398 potential physician
      subjects participated. Patient race/ethnicity had no effect on physician
      prescription of opioids at discharge for African Americans, Hispanics, and
      whites: absolute differences in rates of prescribing opioids at discharge were
      less than 2% for all three conditions presented. Making socially desirable
      information explicit increased the prescribing rates by 4% (95% CI = 0.1% to 8%)
      for the migraine vignette and 6% (95% CI = 3% to 8%) for the back pain vignette.
      CONCLUSIONS: Patient race/ethnicity did not influence physicians' predispositions
      to treatment plans in clinical vignettes. Even knowing that the patient had a
      high-prestige occupation and a primary care provider only minimally increased
      prescribing of opioid analgesics for conditions with few objective findings.

PMID- 14597501
TI  - Motor vehicle crash fatalities among Hispanics in rural North Carolina.
AB  - OBJECTIVES: Deaths from motor vehicle crashes (MVCs) have decreased significantly
      over the past three decades. Unfortunately, few data have been collected
      regarding death rates for MVCs in minority populations. The purpose of this study
      was to compare the death rate of whites versus Hispanics for MVCs in a rural
      environment. METHODS: This study examined one rural county in North Carolina from
      January 1, 1999, to December 31, 1999. A retrospective cohort study was performed
      using the North Carolina State Highway Patrol computerized database of MVCs. Data
      regarding the total number of MVCs, fatalities, alcohol-related deaths, seatbelt
      usage, and cause of the collision were analyzed for both whites and Hispanics.
      Census information regarding population in this region also was obtained from the
      U.S. Bureau of Census. Data were analyzed using a chi-square test, with an alpha
      value of 0.05 used to establish statistical significance. RESULTS: During the
      study period, whites were involved in 2,689 MVCs, compared with 158 MVCs for
      Hispanics. Whites were involved in ten fatal MVCs, compared with seven fatal MVCs
      involving Hispanics. The percent of fatal MVCs for whites was 0.3%, or 10 deaths
      per 2,689 MVCs. In contrast, the percent of fatal MVCs for Hispanics was 4.4%, or
      7 deaths per 158 MVCs; odds ratio (OR) = 12.4, 95% CI = 4.7 to 33.1. The 2000
      Census Report for Pitt County noted a white population of 81,613 and a Hispanic
      population of 4,216. Based on these population data, the death rate for MVCs per
      100,000 population was 12.3 for whites versus 166.0 for Hispanics, OR = 13.6, 95%
      CI = 5.2 to 35.6. Although the cause for this disparity was not determined,
      previous studies suggest that alcohol and decreased seatbelt usage are
      contributing factors. CONCLUSIONS: In this study, the death rates among Hispanics
      for rural MVCs were significantly higher than for whites. The causes of this
      disparity are not clear but are important to define. Only by understanding this
      disparity can we begin to develop appropriate interventions that may prevent
      these deaths.

PMID- 14597502
TI  - Evaluation of race and ethnicity on alcohol and drug testing of adolescents
      admitted with trauma.
AB  - OBJECTIVES: To describe the incidence of alcohol and drug testing in adolescents
      admitted for traumatic injury and to analyze these results with reference to
      race, ethnicity, and gender differences. METHODS: Data were collected on
      adolescents (aged 12 through 17 years) from the National Trauma Data Bank.
      Testing statuses for alcohol and drugs were the two primary outcome variables.
      The results of these tests were the secondary outcome variables. Additional
      casemix variables included: race, ethnicity, gender, age, Glasgow Coma Scale
      score, Injury Severity Score, day and time of arrival, and payment source.
      Hierarchical, multivariable logistic regression models were used to assess the
      relationship of race, ethnicity, and gender with the primary and secondary
      outcome variables. RESULTS: Differences noted in the likelihood of alcohol and
      drug testing among the different racial, ethnic, and gender groups demonstrated
      an increased likelihood of Hispanic males and African American females to receive
      alcohol testing (odds ratio [OR]: 1.48; 95% CI = 1.06 to 2.06; and OR: 1.30; 95%
      CI = 1.01 to 1.67, respectively). Results of testing revealed that females of all
      races were less likely than males to test positive for alcohol and drugs. Drug
      and alcohol testing was more common during evenings, nights, and weekends, as
      well as in the presence of neurologic injury. CONCLUSIONS: Whereas small
      disparities in alcohol and drug testing were noted in some minority race-based
      groupings, systematic racial bias is not evident in adolescent trauma patients.

PMID- 14597503
TI  - The influence of insurance, race, and gender on emergency department disposition.
AB  - OBJECTIVES: To examine the influence of insurance, race, and gender on the
      likelihood of hospitalization among trauma patients. METHODS: Statewide hospital
      discharge and emergency department (ED) visit data collected between 1996 and
      2000 were merged to examine factors that influence hospitalization among patients
      who sustained an injury. Multivariate logistic regression was used to model the
      likelihood of hospitalization as a function of patient, injury, and hospital
      characteristics. RESULTS: Of 1,512,611 patients who presented to an ED in South
      Carolina for treatment of a traumatic injury during the five-year study period,
      8% were hospitalized and 92% were treated and released. One fourth (26%) of the
      study population was uninsured. Insurance, race, and gender were significant
      predictors of hospitalization despite controlling for injury severity,
      comorbidities, age, trauma center level, place of residence, and year of injury.
      Regardless of injury severity, uninsured patients were significantly less likely
      to be hospitalized compared with privately insured patients (odds ratio [OR]
      0.63, 99% CI = 0.62 to 0.65). Among those mildly to moderately injured, patients
      covered by Medicare or other government insurance policies were significantly
      more likely to be admitted compared with those with private coverage (OR 1.46,
      99% CI = 1.41 to 1.52; OR 1.56, 99% CI = 1.36 to 1.78). Finally, among those
      mildly injured, African American females were significantly less likely to be
      admitted compared with white females (OR 0.63, 99% CI = 0.61 to 0.65).
      CONCLUSIONS: These results suggest that the disposition of trauma patients from
      the ED may be influenced by insurance and demographic characteristics in addition
      to the patient's clinical condition.

PMID- 14597504
TI  - Are there disparities in emergency care for uninsured, medicaid, and privately
      insured patients?
AB  - OBJECTIVES: To determine if there are any differences in proportion of high
      acuity care and low-acuity care provided to uninsured, Medicaid-insured, and
      privately insured emergency department (ED) patients. METHODS: This was a
      retrospective, observational study using physician level of service provided as a
      marker for acuity. The study used computerized billing data (2000-2001) from an
      urban, teaching, Level I trauma center with 75,000 visits per year. All uninsured
      and Medicaid patients (age groups: pediatric, <18 years; adult, 18-64 years) were
      compared by physician level of service billed to Blue Cross-Blue Shield (BCBS)
      patients and analyzed using chi-square. Low-acuity care was defined by CPT codes
      99281 and 99282. High-acuity care was defined by CPT codes 99285 and 99291.
      RESULTS: There were 152,379 total ED visits, with 13.2% BCBS (5,273 pediatric,
      14,951 adult), 29.6% Medicaid (20,578 pediatric, 24,511 adult), and 8.1%
      uninsured (1,879 pediatric, 10,405 adult) patients. The percent of pediatric
      BCBS, Medicaid, and uninsured patients receiving low-acuity care was 30%, 35.7%,
      and 35.8% (p < 0.001), respectively; and for high-acuity care, it was 7.8%, 6.1%,
      and 6.8% (p < 0.001), respectively. The proportion of adults within these
      groupings was 13.7%, 13.2%, and 17.9% (p < 0.001) for low-acuity care, and 28.5%,
      22.9%, and 16.7% (p < 0.001) for high-acuity care, respectively. CONCLUSIONS:
      Whereas there were some statistically discerned differences between insurance
      groupings for proportionate receipt of low-acuity care and high-acuity care among
      both the pediatric and adult populations, the magnitude of most differences noted
      was not large, and may not reflect important differences in health care need or
      ED use based on insurance.

PMID- 14597505
TI  - Socioeconomic disparities are negatively associated with pediatric emergency
      department aftercare compliance.
AB  - OBJECTIVES: This study sought to identify demographic, socioeconomic, and
      clinical predictors of aftercare noncompliance by pediatric emergency department
      (ED) patients. METHODS: The authors conducted a prospective, observational study
      of pediatric patients presenting to a university teaching hospital ED from July
      1, 2002, through August 31, 2002. Demographic and clinical information was
      obtained from guardians during the ED visit. Guardians were contacted after
      discharge to determine compliance with ED aftercare instructions. Subjects were
      excluded if they were admitted or if guardians were unavailable or unwilling to
      consent. Data were analyzed using multivariable logistic regression to identify
      predictors of noncompliance from a list of predetermined variables. RESULTS: Of
      the 409 patients enrolled in the study, 111 were prescribed medications and 364
      were given specific follow-up instructions. Subtypes of the variable "insurance
      status" were significantly associated with medication noncompliance in
      multivariable regression analysis. "Insurance status" and "low-acuity discharge
      diagnoses" were significantly associated with follow-up noncompliance.
      CONCLUSIONS: Disparity in health insurance has been shown to be a predictor of
      poor aftercare compliance for pediatric ED patients within the patient
      population.

PMID- 14597506
TI  - Association between insurance status and admission rate for patients evaluated in
      the emergency department.
AB  - OBJECTIVES: To determine if differences exist in hospital and intensive care unit
      (ICU)/operating room admission rates based on health insurance status. METHODS:
      This was a retrospective, cross-sectional study of data from hospital clinical
      and financial records for all 2001 emergency department (ED) visits (80,209) to
      an academic urban hospital. Hospital admission and intensive care unit
      (ICU)/operating room admissions were analyzed, controlling for triage acuity,
      primary complaint, diagnosis, diagnosis-related group (DRG) severity, and
      demographics. Multivariate logistic regression models identified factors
      associated with hospital admission for under insured (self-pay and Medicaid)
      compared with other insured (private health maintenance organization, preferred
      provider organization, worker's compensation, and Medicare) patients. RESULTS:
      Compared with the other insured group, under insured patients were less likely,
      overall, to be admitted to the hospital (odds ratio [OR], 0.82; 95% CI = 0.76 to
      0.90), controlling for all other factors studied. Subgroup analysis of common
      complaints showed under insured patients with a chief complaint of abdominal pain
      (OR, 0.67; 95% CI = 0.55 to 0.80) or headache (OR, 0.61; 95% CI = 0.39 to 0.95)
      had the lowest adjusted ORs for admission to the hospital, compared with other
      insured patients. Under insured patients with DRG of "menstrual and other female
      reproductive system disorders" (OR, 0.17; 95% CI = 0.06 to 0.51) or "esophagitis,
      gastroenteritis, and miscellaneous digestive disorders" (OR, 0.55; 95% CI = 0.28
      to 0.96) also were less likely to be admitted compared with the other insured
      group. No significant differences in ICU/operating room admission rates were
      found between insurance groups. CONCLUSIONS: Whereas there was no difference in
      admission rates to the ICU/operating room by insurance status, this single-center
      study does suggest an association between insurance status and admission to a
      general hospital service, which may or may not be causally related. Factors other
      than provider bias may be responsible for this observed difference.

PMID- 14597507
TI  - Racial and ethnic disparities in health: an emergency medicine perspective.
AB  - Significant disparities exist in health care based on race. Even when controlling
      for socioeconomic factors, minorities still have lower rates of utilization for
      certain procedures, higher mortality rates, and differences in usual source of
      care. There are a multitude of causes for these disparities, including
      differences based on access to care, the patient-doctor relationship, and
      insurance status. This article addresses possible factors that account for
      persistent disparities in health based on race and suggests approaches to
      remedying these disparities. Although many studies have been done on this topic,
      further research is needed to examine factors specifically in the emergency
      department setting.

PMID- 14597508
TI  - Ethics seminars: vulnerable populations in emergency medicine research.
AB  - Regulatory bodies and institutional review boards are increasingly considering
      human subjects who are vulnerable to research not because of their intrinsic
      characteristics, but because of the particular situations or circumstances that
      they bring with them as potential research participants. Several subsets of
      emergency department patients may be considered vulnerable in the research
      setting. This may include patients who are vulnerable because of a medical
      condition, a baseline limitation of intellectual function, a social setting,
      psychosocial stressors, or other factors. These issues should be carefully
      considered when including such patients in research protocols. Special efforts
      should be made to ensure voluntary participation and understanding of the
      purposes and risks of participation.

PMID- 14597509
TI  - The Society for Academic Emergency Medicine position on pediatric care in the
      emergency department.

PMID- 14597511
TI  - Safe and effective.

PMID- 14597513
TI  - The relationship between stereopsis and visual acuity after occlusion therapy for
      amblyopia.
AB  - PURPOSE: To investigate the relationship between visual acuity (VA) and
      stereoacuity after occlusion therapy in patients with various types of amblyopia.
      DESIGN: Retrospective noncomparative case series. PARTICIPANTS: Sixty-one
      children with amblyopia caused by anisometropia with no strabismus (26 children),
      small angle (</=8 prism diopters) or intermittent strabismus (20), or both (15).
      METHODS: All were treated with occlusion therapy. Visual acuity and near
      stereopsis using the Titmus test (Stereo Optical Inc., Chicago, IL) were measured
      at each clinic visit. MAIN OUTCOME MEASURE: The change in near stereopsis
      relative to distance VA after occlusion therapy. RESULTS: Mean age at initiation
      of therapy was 5.1 years (range = 3.5-8) and mean follow-up 52.3 weeks (range =
      13-192). Mean duration of occlusion was 36 weeks (range = 12-102). After
      occlusion treatment, mean VA of all children improved from 0.43 to 0.78
      (P<0.0001), whereas mean stereoacuity improved from 1167.4 seconds of arc to 101
      (P<0.0001). By the last visit, 85.2% (52 of 61) of patients demonstrated at least
      2 lines of improvement in VA. There was a significant linear relationship between
      VA and stereoacuity (P<0.001). The 26 anisometropic patients without strabismus
      enjoyed improvement in VA and stereopsis (P<0.0001) similar to that of the 35
      with small-angle or intermittent strabismus (P<0.0001). CONCLUSIONS: When
      employing occlusion therapy for amblyopia (due to anisometropia, small-angle or
      intermittent strabismus, or a combination), as VA improves, stereopsis generally
      also improves.

PMID- 14597514
TI  - Common forms of childhood exotropia.
AB  - OBJECTIVE: To determine the most common forms of childhood exotropia. DESIGN:
      Retrospective, consecutive, observational case series. PARTICIPANTS: All
      exotropic children (with >/=10 prism diopters) younger than 19 years from a
      predominantly rural Appalachian region evaluated from August 1, 1995 through July
      31, 2001. METHODS: Demographic and clinical data were collected on all patients.
      MAIN OUTCOME MEASURES: The relative proportion of the various forms of childhood
      exotropia. RESULTS: Two hundred thirty-five consecutive children without prior
      surgical treatment were evaluated for exotropia. Of the 235 study children, the
      specific forms of exotropia diagnosed and numbers were as follows: intermittent
      exotropia, 112 (47.7%); exotropia associated with congenital or acquired
      abnormalities of the central nervous system (CNS), 50 (21.3%); convergence
      insufficiency, 27 (11.5%); sensory exotropia, 24 (10.2%); paralytic exotropia, 5
      (2.1%); congenital exotropia, 4 (1.7%); neonatal exotropia that resolved after 4
      months of age, 3 (1.3%), whereas the remaining 10 (4.3%) had an undetermined form
      of exodeviation. CONCLUSIONS: Intermittent exotropia was the most common form of
      divergent strabismus in this population. Exotropia associated with an abnormal
      CNS, convergence insufficiency, and sensory exotropia were also relatively
      common, whereas the congenital, paralytic, and late-resolving neonatal forms were
      uncommon.

PMID- 14597512
TI  - A randomized trial of prescribed patching regimens for treatment of severe
      amblyopia in children.
AB  - OBJECTIVE: To compare full-time patching (all hours or all but 1 hour per day) to
      6 hours of patching per day, as prescribed treatments for severe amblyopia in
      children younger than 7 years. DESIGN: Prospective, randomized multicenter
      clinical trial (32 sites). PARTICIPANTS: One hundred seventy-five children
      younger than 7 years with amblyopia in the range of 20/100 to 20/400.
      INTERVENTION: Randomization either to full-time patching or to 6 hours of
      patching per day, each combined with at least 1 hour of near-visual activities
      during patching. MAIN OUTCOME MEASURE: Visual acuity in the amblyopic eye after 4
      months. RESULTS: Visual acuity in the amblyopic eye improved a similar amount in
      both groups. The improvement in the amblyopic eye acuity from baseline to 4
      months averaged 4.8 lines in the 6-hour group and 4.7 lines in the full-time
      group (P = 0.45). CONCLUSION: Six hours of prescribed daily patching produces an
      improvement in visual acuity that is of similar magnitude to the improvement
      produced by prescribed full-time patching in treating severe amblyopia in
      children 3 to less than 7 years of age.

PMID- 14597515
TI  - Horizontal rectus tenotomy in patients with congenital nystagmus: results in 10
      adults.
AB  - OBJECTIVE: We wished to determine the effectiveness of horizontal rectus tenotomy
      in changing the nystagmus of patients with congenital nystagmus and, secondarily,
      how their visual function changed. DESIGN: This was a prospective,
      noncomparative, interventional case series. PARTICIPANTS: Ten adult patients with
      varied associated sensory defects and oculographic subtypes of congenital
      nystagmus (including asymmetric periodic or aperiodic alternating nystagmus) and
      no nystagmus treatment options. METHODS: By using standard surgical techniques,
      simple tenotomy of all four horizontal recti with reattachment at the original
      insertion was accomplished. Search-coil eye movement recordings and clinical
      examinations were performed before and 1, 6, 24, and 52 weeks after surgery. MAIN
      OUTCOME MEASURES: The primary outcome measure was the expanded nystagmus acuity
      function, obtained in "masked" fashion directly from ocular motility recordings.
      Secondary outcomes included breadth of null zones, preoperative and postoperative
      masked measures of visual acuity (Early Treatment Diabetic Retinopathy Study
      [ETDRS] chart), and the National Eye Institute Visual Function Questionnaire (NEI
      VFQ-25). RESULTS: At 1 year after tenotomy and under binocular conditions, 9 of
      10 patients had persistent, significant postoperative increases in the expanded
      nystagmus acuity function of their fixing (preferred) eye; 1 remained high, and 1
      was not tested under the same conditions. Average foveation times increased in
      all 9 fixing (preferred) eyes. Binocular visual acuity measured with the ETDRS
      chart increased in 5 patients and was unaffected in five, whereas the NEI-VFQ-25
      showed an improvement in vision-specific mental health in 9 patients. There were
      no adverse events. Tenotomy also radically changed the periodicity of one
      patient's asymmetric periodic or aperiodic alternating nystagmus. CONCLUSIONS: In
      9 of 10 adult patients with clinical and oculographic variations in their
      congenital nystagmus, tenotomy resulted in significant improvements in a
      nystagmus measure and subjective visual functions.

PMID- 14597516
TI  - A phase III, multicenter, randomized, placebo-controlled clinical trial of
      topical aminocaproic acid (Caprogel) in the management of traumatic hyphema.
AB  - OBJECTIVE: To determine the safety and efficacy of topical aminocaproic acid
      (Caprogel) in the management of traumatic hyphema. DESIGN: Multicenter,
      randomized, double-masked, placebo-controlled clinical trial. PARTICIPANTS: A
      total of 51 patients participated in this trial (power = 36%, 2-tailed test).
      INTERVENTION: Patients presenting with traumatic hyphema were randomly assigned
      to 5-day treatment with topical aminocaproic acid or a placebo gel. Patients were
      monitored daily with ocular examination and vital sign testing for the 5 days of
      treatment and at 24 and 48 hours after treatment. General physical examination
      and laboratory testing were performed at baseline and day 5. MAIN OUTCOME
      MEASURES: The main efficacy variable was the rate of rebleeding. Secondary
      efficacy variables included time to hyphema clearance, intraocular pressure, time
      to secondary hemorrhage, and visual acuity. Safety variables included adverse
      events, vital signs, and laboratory measurements. RESULTS: Rebleeding occurred in
      30% of the placebo group (8 of 27; 95% confidence interval [CI] = 14-50%), versus
      8% of the treatment group (2 of 24; 95% CI = 1-27%), for an estimated continuity
      corrected difference in percentage of patients with bleeding of 17% (95% CI = -3
      38%). Secondary efficacy variables were similar in the groups, except that there
      was a trend towards more visual improvement in the topical aminocaproic acid
      group (54%) than in the placebo group (30%) at the last measurement (P = 0.08).
      Adverse events were similar. CONCLUSIONS: This study provides evidence that
      topical aminocaproic acid is safe and demonstrates trends towards reducing the
      rebleeding rate in the management of traumatic hyphema. However, because the
      study was terminated before complete enrollment, more definitive recommendations
      will require a larger trial.

PMID- 14597517
TI  - Telemedicine approach to screening for severe retinopathy of prematurity: a pilot
      study.
AB  - PURPOSE: To evaluate the use of remote reading of digital retinal photographs in
      the diagnosis of severe (referral-warranted) retinopathy of prematurity (ROP)
      during longitudinal screening for ROP. STUDY DESIGN: Prospective, longitudinal
      cohort study. SUBJECTS: Forty-four consecutive premature infants at risk for ROP.
      METHODS: All infants were examined longitudinally, over a series of examinations,
      by indirect ophthalmoscopy (gold standard) and digital photography using the
      RetCam-120 Digital Retinal Camera (Massie Research Laboratories Inc., Dublin, CA)
      equipped with an ROP lens. Images were stored and read remotely by a masked
      reader. Referral-warranted ROP was defined as ROP in zone 1, the presence of plus
      disease or the presence of any stage 3 ROP. We determined whether and when
      referral-warranted ROP was diagnosed for each eye, of each infant, on each
      examination, during the course of each of the infant's screening. RESULTS: Severe
      (referral-warranted) ROP was diagnosed in 23 eyes by indirect ophthalmoscopy
      during their series of examinations. Digital photography had a sensitivity of
      100% and a specificity of 96% in detecting referral-warranted ROP. The positive
      predictive value of digital photography was 92%, and the negative predictive
      value was 100%. In 87% of eyes, referral-warranted ROP was diagnosed by digital
      photography before or at the same time as indirect ophthalmoscopy. CONCLUSIONS:
      Longitudinal remote reading of digital photographs using the RetCam-120 system
      has excellent specificity and sensitivity in detecting referral-warranted ROP.
      This pilot study has shown that remote reading of digital photographs has promise
      for telemedicine strategies in ROP screening.

PMID- 14597518
TI  - Retinal vascular abnormalities in persons with type 1 diabetes: the Wisconsin
      Epidemiologic Study of Diabetic Retinopathy: XVIII.
AB  - PURPOSE: To describe the distribution of retinal vascular characteristics and
      their correlates in people with type 1 diabetes. DESIGN: Population-based study
      with baseline cross-sectional findings. PARTICIPANTS: Nine hundred ninety-six
      persons who were diagnosed with diabetes before 30 years of age and who were
      taking insulin in an 11-county area in south-central Wisconsin participated in
      the baseline examination from 1980 to 1982. In addition, 225 persons without
      diabetes participated. METHODS: Retinal photographs of 7 standard fields were
      taken; lightbox grading was performed to determine arteriovenous (A/V) nicking
      and focal retinal arteriolar narrowing. Computer-assisted grading was performed
      from a digitized image of field 1 to determine central retinal arteriolar
      equivalent (CRAE), central retinal venular equivalent (CRVE), and the arteriole
      to-venule ratio (AVR). MAIN OUTCOME MEASURES: Frequency and distribution of A/V
      nicking, CRAE, CRVE, AVR, and focal retinal arteriolar narrowing. RESULTS: In
      multivariate analyses, retinopathy severity, mean arterial blood pressure,
      presence of gross proteinuria, glycosylated hemoglobin, and history of
      cardiovascular disease were associated with CRAE. Retinopathy severity, age, mean
      arterial blood pressure, duration of diabetes, glycosylated hemoglobin level, and
      body mass index were associated with CRVE. With the exception of glycosylated
      hemoglobin, similar factors were associated with AVR. Age (odds ratio [OR] per 10
      years, 2.43 and 2.02) and retinopathy severity (OR per level, 1.14 and 1.21) were
      associated with focal retinal arteriolar narrowing and A/V nicking, respectively.
      In persons >/=18 years of age, smoking was associated with CRAE, CRVE, and A/V
      nicking (OR, 2.67), but not with AVR or focal arteriolar narrowing. CONCLUSIONS:
      This study documented the frequency and distribution of retinal vascular
      characteristics and their relationships to various factors in persons with type 1
      diabetes.

PMID- 14597519
TI  - Histopathology and regression of retinal hard exudates in diabetic retinopathy
      after reduction of elevated serum lipid levels.
AB  - PURPOSE: To describe a regression of retinal hard exudates in 2 patients with
      diabetic maculopathy, and to report immunohistologic findings reflecting lipid
      deposition in the retina. DESIGN: Two interventional case reports. METHODS: Two
      patients with exudative diabetic maculopathy were treated to normalize serum
      lipids. Histologic examination and immunohistochemistry of each patient's eyes
      were performed to assess the localization of apolipoprotein B and cholesteryl
      ester, both of which are principal components of low-density lipoprotein.
      RESULTS: Both patients showed a dramatic regression of retinal hard exudates
      after correction of dyslipidemia. Histopathology revealed diffuse lipids and
      cholesteryl ester in the retina. Apolipoprotein B and macrophages were
      colocalized in the perivascular space. CONCLUSIONS: The regression of hard
      exudates was most likely due to the aggressive lipid lowering in both patients.
      The novel histopathologic findings of hard exudate and diabetic maculopathy are
      similar to the pathologic changes observed in larger atherosclerotic lesions,
      except that they occur in the intraretinal perivascular space.

PMID- 14597520
TI  - Polymerase chain reaction detection of Neisseria meningitidis in the intraocular
      fluid of a patient with endogenous endophthalmitis but without associated
      meningitis.
AB  - PURPOSE: To report a patient with Neisseria meningitidis endophthalmitis without
      associated meningitis with full visual recovery, with early detection of the
      microorganism using polymerase chain reaction (PCR) analysis. DESIGN:
      Retrospective, observational case report. PARTICIPANTS: One patient with
      endogenous endophthalmitis. METHODS: Polymerase chain reaction analysis and
      culture of the intraocular fluid sample. Polymerase chain reaction analysis was
      performed with a universal (16S rRNA) primer set to detect bacterial DNA, and
      subsequently a specific probe was used to detect Neisseria species DNA. RESULTS:
      The 16S rRNA primers detected bacterial DNA, the specific probe detected
      Neisseria species DNA, and culture was positive for Neisseria meningitidis
      serotype C. CONCLUSIONS: A universal bacterial PCR can be very helpful for the
      diagnosis of endogenous bacterial endophthalmitis at an early stage of the
      disease.

PMID- 14597521
TI  - Medical malpractice predictors and risk factors for ophthalmologists performing
      LASIK and photorefractive keratectomy surgery.
AB  - PURPOSE: To identify physician predictors in LASIK and photorefractive
      keratectomy (PRK) surgery that correlate with a higher risk for malpractice
      liability claims and lawsuits. DESIGN: Retrospective, longitudinal, cohort study.
      PARTICIPANTS AND METHODS: A comparison of physician demographic and practice
      pattern data of 100 consecutive Ophthalmic Mutual Insurance Company (OMIC) LASIK
      and PRK claims and lawsuits with demographic and practice pattern data for all
      active refractive surgeons insured by OMIC between 1996 to 2002 was made.
      Background information and data were obtained from OMIC underwriting
      applications, a physician practice pattern survey, and claims file records. Using
      an outcome of whether or not a physician had a history of a claim or lawsuit,
      logistic regression analyses were used separately for each predictor as well as
      controlling for refractive surgery volume. MAIN OUTCOME MEASURE: Malpractice
      claim or lawsuit for performance of PRK or LASIK surgery. RESULTS: Logistic
      regression analysis demonstrated that the most important predictor of filing a
      claim was surgical volume, with those performing more surgery having a greater
      risk of incurring a claim (odds ratio [OR] = 31.4 for >1000 surgeries/year versus
      0-20 surgeries/year, 95% confidence interval [CI] = 7.9-125, P = 0.0001). Having
      one or more prior claim was the only other predictor examined that remained
      statistically significant after controlling for patient volume (OR = 6.4, 95% CI
      = 2.5-16.4, P = 0.0001). Physician gender, advertising use, preoperative time
      spent with patient, and comanagement seemed to be strong predictors in
      multivariate analyses when surgical volume was greater than 100 cases per year.
      CONCLUSION: The chances for incurring a malpractice claim or lawsuit for PRK or
      LASIK correlate significantly with higher surgical volume and a history of a
      claim or lawsuit. Additional risk factors that increase in importance with higher
      surgical volume include physician gender, advertising use, preoperative time
      spent with the patient, and comanagement with optometrists. These findings may be
      used in the future to help improve the quality of care for patients undergoing
      refractive surgery and to provide data for underwriting criteria and risk
      management protocols to manage proactively and perhaps reduce the risk for claims
      and lawsuits against refractive surgeons.

PMID- 14597522
TI  - Ten-year follow-up of epikeratophakia for the correction of high myopia.
AB  - OBJECTIVE: To determine the long-term functional results of epikeratophakia for
      myopic patients. DESIGN: Retrospective, noncomparative, interventional case
      series. PARTICIPANTS: Twenty-two patients (32 eyes; average age, 43+/-6 years)
      who underwent epikeratophakia surgery for high myopia. Mean preoperative myopia
      was -18.74+/-9.16 diopters (D; range, -7 D to -49 D). Follow-up was 12+/-2 years.
      MAIN OUTCOME MEASURES: Uncorrected visual acuity (UCVA), best-corrected visual
      acuity (BCVA), change in mean keratometry, visual acuity under glare conditions,
      BCVA versus potential acuity meter reading, and patient satisfaction with the
      visual outcome. RESULTS: Mean preoperative UCVA increased from 20/800+/-20/400
      (range, counting fingers-20/400) to 20/80+/-20/200 (range, 20/250-20/32) in 24
      eyes. Mean preoperative BCVA of 20/32+/-20/64 increased only in five eyes,
      whereas six eyes had no change and 18 eyes had a more than one line loss of
      Snellen BCVA. Mean preoperative keratometry reading decreased from 43.67+/-0.90 D
      (range, 41.0-46.25 D) to 37.40+/-2.92 D (range, 29.43-47.68 D). In the presence
      of glare, mean BCVA decreased to 20/100+/-20/100 (range, counting fingers-20/32).
      Potential acuity meter (PAM) readings were significantly (P<0.05) higher than
      BCVA. Mean PAM reading was 20/25+/-20/100 (range, 20/100-20/16). Seven patients
      (11 eyes) were extremely satisfied with the operative result more than 10 years
      after the operation, whereas four patients (four eyes) were not satisfied at all.
      CONCLUSIONS: Epikeratophakia for the correction of myopia improved UCVA
      significantly, but BCVA decreased. The removal of the lenticules in patients who
      were not satisfied with their visual acuity was uncomplicated, and acceptable
      vision could be achieved with either contact lenses or intraocular lens
      implantation.

PMID- 14597523
TI  - Outcome after treatment of ametropia with implantable contact lenses.
AB  - OBJECTIVE: To evaluate long-term results after insertion of implantable contact
      lenses (ICLs) in phakic eyes. DESIGN: Prospective, noncomparative, interventional
      case series. PARTICIPANTS: Seventy-five phakic eyes (65 myopic, 10 hyperopic
      eyes) of 45 patients aged 21.7 to 60.6 years were included. INTERVENTION: STAAR
      Collamer Implantable Contact Lenses (STAAR Surgical Inc., Nidau, Switzerland)
      were implanted for correction of high myopia and hyperopia. MAIN OUTCOME
      MEASURES: Uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA),
      and intraocular pressure (IOP) were determined. Presence of lens opacification
      and the distance between the ICL and the crystalline lens were assessed by slit
      lamp examination before surgery and at 1, 3, 6 months, and yearly after lens
      implantation. RESULTS: Preoperative mean spherical equivalent was -16.23+/-5.29
      diopters (D) for myopic eyes and +7.88 +/-1.46 D for hyperopic eyes. After ICL
      implantation, mean residual refractive error was -1.77+/-2.17 D in myopic
      patients and +0.44+/-0.69 D in hyperopic patients. Preoperative mean UCVA was
      Snellen 0.03+/-0.03 for myopic patients and Snellen 0.12+/-0.16 for hyperopic
      patients. Preoperative mean BCVA was Snellen 0.49+/-0.23 for myopic patients and
      Snellen 0.82+/-0.23 for hyperopic patients. After ICL implantation, mean UCVA up
      to the end of individual observation time was Snellen 0.36+/-0.36 for myopic
      patients and Snellen 0.58+/-0.28 for hyperopic patients. Mean BCVA was Snellen
      0.73+/-0.26 for myopic and Snellen 0.80+/-0.24 for hyperopic patients. Mean
      preoperative IOP was 14.2+/-2.7 mmHg, and mean postoperative IOP was 13.46+/-2.1
      mmHg over all follow-up investigations. The main complication was the development
      of subcapsular anterior opacifications of the crystalline lens in 25 eyes
      (33.3%), 2 of which showed direct contact to the ICL. Eleven eyes (14.7%) were
      stable in opacification and 14 eyes (18.7%) had progressive opacifications. The
      median time to opacification was 27.1 months. In 8 patients (10.7%), the
      subjective visual impairment mandated cataract surgery. CONCLUSIONS: The most
      significant long-term complication after ICL implantation is the formation of
      opacifications of the crystalline lens with the risk of the necessity of
      subsequent cataract surgery (10.7%). Old age, female gender, and contralateral
      opacification are independent significant risk factors for early formation of
      opacifications in this patient group.

PMID- 14597524
TI  - Impact of graft diameter on corneal power and the regularity of postkeratoplasty
      astigmatism before and after suture removal.
AB  - OBJECTIVE: To assess the impact of graft diameter on corneal curvature before and
      after removal of a double-running suture after nonmechanical penetrating
      keratoplasty (PK). DESIGN: Prospective, nonrandomized, comparative (self
      controlled) single-center clinical trial. PATIENTS: Four hundred eighty-nine eyes
      with "two sutures in" and 308 eyes with "all sutures out" (mean age, 52+/-19
      years) were included. The diagnoses were keratoconus (48%), Fuchs' and stromal
      dystrophies (31%), aphakic or pseudophakic bullous keratopathy (11%), and scars
      (10%). INTERVENTIONS: In all eyes, a central trephination was performed (donor
      trephination from the epithelial side) using the 193-nm Meditec excimer laser
      (Carl Zeiss Meditec, Jena, Germany) along metal masks with eight "orientation
      teeth/notches." Diameters were 8.0 mm, 7.5 mm, and 7.0 mm with a graft oversize
      of 0.1 mm. In 29% of eyes, additional cataract, intraocular lens surgery, or both
      were performed simultaneously. In all eyes, a double-running 10-0 nylon suture
      was applied. Zeiss keratometry and TMS-1 topography analysis were performed
      before removal of the first suture (14+/-4 months) and at least 6 weeks after
      removal of the second suture (20+/-4 months), but before any additional surgery,
      such as cataract extraction or refractive keratotomies. MAIN OUTCOME MEASURES:
      Topographic central corneal power (CP; keratometric diopters), keratometric
      astigmatism (KA), surface regularity index (SRI), and surface asymmetry index
      (SAI). The regularity of keratometry mires was recorded semiquantitatively from 0
      = regular to 3 = not measurable (as published earlier). RESULTS: With both
      sutures in, median CP in 7.0-mm (42.0 diopters [D]; P = 0.04) and in 7.5-mm
      grafts (42.3 D; P = 0.007) was significantly lower than in 8.0-mm grafts (43.0
      D). Keratometric astigmatism did not differ between groups (3.0 D vs. 3.0 D vs.
      2.7 D). The SRI (1.66 vs. 1.43 vs. 1.11) and SAI (1.55 vs. 1.24 vs. 0.85)
      decreased significantly with increasing diameter. The proportion of regular
      keratometry mires (13% vs. 17% vs. 29%) increased, and the proportion of not
      measurable keratometries (45% vs. 18% vs. 9%) decreased with increasing diameter.
      With all sutures out, CP in 7.0-mm grafts (40.4 D) was significantly smaller than
      in 7.5-mm (43.6 D; P = 0.04) and 8.0-mm grafts (43.3 D; P = 0.04). Again, KA did
      not differ between groups (3.0 D vs. 3.2 D vs. 3.0 D). The SRI (1.40 vs. 1.09 vs.
      0.84) and SAI (1.24 vs. 0.83 vs. 0.62) decreased significantly with increasing
      diameter. The proportion of regular keratometry mires (5% vs. 31% vs. 52%)
      increased, and the proportion of not measurable keratometries (42% vs. 11% vs.
      4%) decreased with increasing diameter. CONCLUSIONS: After PK, a smaller graft
      diameter results in a flatter curvature and a higher degree of topographic
      irregularity, but not in higher net astigmatism. After suture removal, graft
      topography tends to regularize, whereas the principal differences between
      diameters do persist.

PMID- 14597525
TI  - Human fibrin tissue adhesive for sutureless lamellar keratoplasty and scleral
      patch adhesion: a pilot study.
AB  - PURPOSE: To determine whether a fibrin adhesive can facilitate the performance of
      sutureless lamellar keratoplasty and attachment of amnion to bare sclera. DESIGN:
      Prospective, noncomparative case series. PARTICIPANTS: Six patients, 5 of whom
      underwent lamellar keratoplasty and 1 who received an amniotic patch of the
      sclera and cornea. Institutional review board approval was not required for these
      therapeutic treatments. METHODS: In 5 patients, the epithelium was removed from
      the corneal surface, a free cap, 200- micro m thick, was cut with a
      microkeratome, and a human fibrin tissue adhesive (Tisseel VH Fibrin Sealant;
      Baxter Healthcare Corporation, Glendale, CA) was applied to the cut surface of
      the corneal stroma. A 200- micro m thick, microkeratome-cut lamellar graft was
      placed in the stromal bed without sutures, and a bandage soft contact lens was
      applied. The lens was left in place for 1 week and then removed. In 1 patient,
      the adhesive was applied to bare sclera for attachment of amniotic membrane after
      removal of a conjunctival melanosis. All patients were followed up for 3 months
      after surgery. MAIN OUTCOME MEASURES: Tissue adhesion, corneal clarity, and
      visual acuity. RESULTS: All 5 lamellar grafts healed and remained clear, although
      final visual acuity varied with visual potential and astigmatism. The amniotic
      membrane graft also adhered well to the bare sclera. CONCLUSIONS: The fibrin
      adhesive provided satisfactory attachment without sutures for lamellar
      keratoplasty and amniotic patching. It should be effective for sealing of clear
      cornea incisions, LASIK flaps, and conjunctival and skin grafts. An adhesive that
      has been designed specifically for ophthalmic applications and is more convenient
      to use would be desirable.

PMID- 14597527
TI  - Visual field and optic disc progression in patients with different types of optic
      disc damage: a longitudinal prospective study.
AB  - OBJECTIVE: To evaluate the incidence of visual field and optic disc progression
      in glaucoma patients with distinct patterns of optic disc damage. DESIGN:
      Prospective, observational case series. PARTICIPANTS: One hundred five patients
      with open-angle glaucoma. METHODS: Baseline optic disc photographs of 105 study
      eyes of 105 patients were reviewed by 2 masked observers and classified according
      to patterns of disc damage into the following categories: focal, myopic, senile
      sclerotic, and generalized disc damage. Patients were followed up every 6 months
      with standard automated perimetry (SAP), high-pass resolution perimetry (HRP),
      and scanning laser tomography (SLT) with the Heidelberg Retina Tomograph. MAIN
      OUTCOME MEASURES: Visual field (SAP and HRP) and optic disc (SLT) progression
      were determined according to predefined criteria. RESULTS: Twenty-four eyes were
      classified into the focal, 8 into the myopic, 12 into the senile sclerotic, and
      28 into the generalized group. Eyes from 33 patients could not be classified by
      the observers into any of these groups and were excluded from further analysis.
      Although intraocular pressure during follow-up was similar among the four groups,
      some differences in frequency of progression were observed. Patients with senile
      sclerotic discs had the lowest rates of visual field progression (both with SAP
      and HRP) and optic disc progression, although the differences were significant
      only for optic disc progression (P = 0.05). CONCLUSIONS: Patients with senile
      sclerotic discs showed a tendency towards less visual field and optic disc
      progression when compared with patients with other types of disc damage.

PMID- 14597526
TI  - Fungal infection of sutureless self-sealing incision for cataract surgery.
AB  - PURPOSE: To report the clinical picture and outcome of fungal infection of self
      sealing wounds in cataract surgery. DESIGN: Retrospective noncomparative case
      series. PARTICIPANTS: Seven postoperative cataract patients. METHODS: Seven
      consecutive patients who underwent cataract surgery in different locations in
      India and developed microbiologically proven fungal infection of the surgical
      wound were included. All were managed at a tertiary eye care center in India
      between May 2001 and April 2002. MAIN OUTCOME MEASURES: The data reviewed
      included patient age, gender, onset of symptoms after surgery, examination
      findings at the time of onset of symptoms and referral, laboratory workup,
      treatment, and outcome. The cataract surgeons involved were contacted to
      determine their cataract practice and to determine any possible breach in the
      sterile technique. RESULTS: The median interval to onset of symptoms after
      cataract surgery was 5.0 days (mean, 5.8 days; range, 3-9 days). The initial
      diagnoses at the time of onset of symptoms were keratitis (n = 3), scleritis (n =
      1), and excessive anterior chamber reaction (n = 3). The last 4 patients were
      treated with topical and/or systemic corticosteroid therapy before referral. All
      cases subsequently developed deep keratitis. Specimens for microbiology workup
      were obtained by scrapings (n = 6), corneoscleral biopsy (n = 4), and anterior
      chamber paracentesis (n = 4). Organisms identified were Aspergillus flavus (n =
      2), Aspergillus terreus (n = 2), Aspergillus spp. (n = 2), and Candida albicans
      (n = 1). The infection resolved with medical therapy in 2 cases; the final visual
      acuity was 20/125 in one case and 20/20 in the other case. The infection
      progressed to endophthalmitis in 5 eyes, resulting in complete loss of vision.
      The source of infection could not be identified in any case. CONCLUSIONS:
      Infection of self-sealing tunnel incision for cataract surgery is a diagnostic
      and therapeutic challenge.

PMID- 14597529
TI  - Cystic bleb formation and related complications in limbus- versus fornix-based
      conjunctival flaps in pediatric and young adult trabeculectomy with mitomycin C.
AB  - OBJECTIVE: Comparison of fornix- and limbus-based conjunctival flaps with respect
      to cystic bleb-related complications of trabeculectomy with high-dose mitomycin C
      (MMC) in pediatric and young adult glaucoma. DESIGN: Retrospective nonrandomized
      comparative interventional case series. PARTICIPANTS: Thirty-seven patients.
      METHODS: Identification of patients aged <30 years from operating theater records
      from 1995 and 1996 of the Moorfields Pediatric Glaucoma Service who had
      trabeculectomy with an MMC concentration of >/=0.4 mg/ml. Over a 2-year period,
      37 consecutive operations matching these criteria were performed by a single
      surgeon: 20 with a limbus-based flap and 17 with a fornix-based flap. Except for
      the conjunctival incision and associated alteration in antimetabolite application
      and wound closure, the surgical technique was not significantly different between
      the groups. MAIN OUTCOME MEASURES: Bleb evolution and complications. RESULTS: The
      age at time of surgery, MMC concentration, history of one or more previous
      surgeries, and follow-up were similar in the 2 groups. The risk of cystic bleb
      formation was greater in the limbus-based flap group (90% in the limbus-based
      group vs. 29% in the fornix-based group; P<0.001). Late hypotony and bleb-related
      ocular infection were more common in the limbus-based flap group (P<0.05) and
      occurred earlier. There were four episodes of bleb-related infection (20%) in the
      limbus-based group (three of these [15%] were bleb-related endophthalmitis) and
      none in the fornix-based group. CONCLUSIONS: In pediatric and young adult
      trabeculectomy with high doses of MMC, limbus-based flaps may be more likely to
      develop serious bleb-related complications and may develop these earlier than
      fornix-based flaps. The higher rates of complications could be attributable to
      the differences in bleb morphology, with limbus-based flap cases more likely to
      develop cystic blebs.

PMID- 14597528
TI  - Retinal nerve fiber layer thickness measured with optical coherence tomography is
      related to visual function in glaucomatous eyes.
AB  - PURPOSE: To determine the relationship between areas of glaucomatous retinal
      nerve fiber layer thinning identified by optical coherence tomography and areas
      of decreased visual field sensitivity identified by standard automated perimetry
      in glaucomatous eyes. DESIGN: Retrospective observational case series.
      PARTICIPANTS: Forty-three patients with glaucomatous optic neuropathy identified
      by optic disc stereo photographs and standard automated perimetry mean deviations
      >-8 dB were included. METHODS: Participants were imaged with optical coherence
      tomography within 6 months of reliable standard automated perimetry testing. MAIN
      OUTCOME MEASURES: The location and number of optical coherence tomography clock
      hour retinal nerve fiber layer thickness measures outside normal limits were
      compared with the location and number of standard automated perimetry visual
      field zones outside normal limits. Further, the relationship between the
      deviation from normal optical coherence tomography-measured retinal nerve fiber
      layer thickness at each clock hour and the average pattern deviation in each
      visual field zone was examined by using linear regression (R(2)). RESULTS: The
      retinal nerve fiber layer areas most frequently outside normal limits were the
      inferior and inferior temporal regions. The least sensitive visual field zones
      were in the superior hemifield. Linear regression results (R(2)) showed that
      deviation from the normal retinal nerve fiber layer thickness at optical
      coherence tomography clock hour positions 6 o'clock, 7 o'clock, and 8 o'clock
      (inferior and inferior temporal) was best correlated with standard automated
      perimetry pattern deviation in visual field zones corresponding to the superior
      arcuate and nasal step regions (R(2) range, 0.34-0.57). These associations were
      much stronger than those between clock hour position 6 o'clock and the visual
      field zone corresponding to the inferior nasal step region (R(2) = 0.01).
      CONCLUSIONS: Localized retinal nerve fiber layer thinning, measured by optical
      coherence tomography, is topographically related to decreased localized standard
      automated perimetry sensitivity in glaucoma patients.

PMID- 14597530
TI  - Otago Glaucoma Surgery Outcome Study: factors controlling capsule fibrosis around
      Molteno implants with histopathological correlation.
AB  - OBJECTIVE: To describe the histopathology of Molteno implant capsules in cases of
      primary and secondary glaucoma and to correlate them with surgical technique and
      clinical outcomes in quiet eyes. DESIGN: Human tissue study with
      clinicopathological correlation. MATERIALS: Seventy-five autopsy eyes or surgical
      pathology specimens obtained between 4 days and 23 years after insertion of
      Molteno implants were studied. Basic histologic features common to all bleb
      capsules were described, and the thickness was measured in 28 specimens from
      quiet eyes. MAIN OUTCOME MEASURES: Histologic features of capsules, including
      wall thickness, distribution of inflammatory cells, and presence or absence of
      fibrodegeneration, were assessed by light microscopy. RESULTS: Without aqueous
      flow (first stage of 2-stage insertion), the episcleral plates of Molteno
      implants were encapsulated by a very thin (20-60 micro m) avascular collagenous
      layer. The second stage of 2-stage insertion, with delayed drainage of aqueous
      and early temporary postoperative intraocular pressure (IOP) increase to 25 to 35
      mmHg, produced thin (190-250 micro m) permeable capsules with fewer fibrovascular
      than fibrodegenerative components. Insertion of nonligatured implants with
      immediate aqueous flow produced thicker capsules (300-600 micro m) composed of an
      outer fibrovascular layer and an inner fibrodegenerative layer of approximately
      equal thickness. Three-stage insertion of modified Molteno implants with
      temporary externalization of aqueous flow onto the conjunctival surface and
      postoperative IOP not exceeding 12 mmHg produced the thickest (375-700 micro m)
      heavily fibrosed and impermeable capsules composed entirely of dense
      fibrovascular tissue without a fibrodegenerative layer. CONCLUSIONS: Capsules
      around functioning Molteno implants evolved through a series of histologic
      stages. Without aqueous flow, the episcleral plate of the implant stimulated
      encapsulation by a thin avascular collagenous layer. With aqueous flow, an
      immediate inflammatory reaction developed in the episcleral connective tissues
      that included collagenous and vascular components. After a variable delay, a
      fibrodegenerative process developed in the deeper layers of the capsule. The
      fibrodegenerative process may depend on sufficient increases of IOP for aqueous
      to displace interstitial tissue fluid from the deeper layers of the capsule. The
      final thickness and permeability of the capsule probably depend on the relative
      intensity and timing of these opposing processes, which were influenced by
      surgical technique and postoperative management.

PMID- 14597531
TI  - Transpupillary thermotherapy versus plaque radiotherapy for suspected choroidal
      melanomas.
AB  - PURPOSE: To examine the outcomes and complications of transpupillary
      thermotherapy for treatment of small choroidal melanomas. DESIGN: Retrospective
      case-matched comparative study and retrospective observational study.
      PARTICIPANTS: The case-matched study consisted of 36 patients treated with either
      transpupillary thermotherapy or plaque radiotherapy (18 patients per group). The
      observational study consisted of 21 patients treated with transpupillary
      thermotherapy alone (primary transpupillary thermotherapy) and 9 patients treated
      with transpupillary thermotherapy plus plaque radiotherapy (adjuvant
      transpupillary thermotherapy). MAIN OUTCOME MEASURES: Visual acuity, local tumor
      control, and metastasis. RESULTS: The case-matched groups did not differ
      significantly with respect to age, gender, initial visual acuity, tumor location,
      or length of follow-up (mean, 33 months for transpupillary thermotherapy vs. 40
      months for plaque radiotherapy). There was no significant difference in final
      visual acuity (P = 0.810) or postoperative visual acuity change (P = 0.919)
      between the 2 groups. In the observational study, the mean follow-up was 32
      months (range, 4-58 months). Indications for primary transpupillary thermotherapy
      included documented growth (10 patients) and the presence of >/=3 risk factors
      for growth (11 patients). Retinal complications occurred in 16 patients (76%).
      The mean posttreatment visual acuity change was minus 2 lines (range, minus 9 to
      plus 7 lines). Local failure occurred in 6 patients (29%). Local failure was
      associated with an increased number of transpupillary thermotherapy spots per
      session (P = 0.023) and decreased tumor pigmentation (P = 0.001). Indications for
      adjuvant transpupillary thermotherapy included tumor radioresistance (6 patients)
      and the presence of risk factors for local failure (3 patients). All 9 tumors
      that received adjuvant transpupillary thermotherapy regressed rapidly, with no
      local failures. The mean postoperative visual acuity change was -1.9 lines
      (range, -9 to +5 lines). No patient in either study developed metastasis.
      CONCLUSIONS: The recent interest in transpupillary thermotherapy as primary
      therapy for choroidal melanoma is based largely on the assumption that
      transpupillary thermotherapy may provide better visual outcomes than plaque
      radiotherapy. However, this study found no significant difference in visual
      outcomes between transpupillary thermotherapy and plaque radiotherapy. Further,
      the local failure rate with transpupillary thermotherapy was substantially higher
      than with plaque radiotherapy. The most promising role for transpupillary
      thermotherapy seems to be as an adjunct to plaque radiotherapy. The appropriate
      indications for transpupillary thermotherapy in the management of choroidal
      melanoma need to be re-evaluated.

PMID- 14597533
TI  - Choroidal vascular changes after transpupillary thermotherapy for choroidal
      melanoma.
AB  - OBJECTIVE: To evaluate choroidal vascular alterations after transpupillary
      thermotherapy used as the sole treatment for choroidal melanoma. DESIGN:
      Prospective noncomparative interventional case series. PARTICIPANTS: Forty-five
      eyes of 45 patients affected by malignant choroidal melanoma treated with
      transpupillary thermotherapy alone with more than 1 year of follow-up.
      INTERVENTION: Transpupillary thermotherapy was performed through a panfunduscopic
      contact lens using an 810-nm diode laser. MAIN OUTCOME MEASURES: Dynamic/static
      fluorescein and indocyanine green angiography were performed at scheduled
      intervals (24 hours, at 3-month intervals during the first year, and every 6
      months thereafter) after transpupillary thermotherapy. Visual acuity, clinical
      evaluation, fundus photographs, and ultrasonographic examination were also
      performed. RESULTS: The mean follow-up was 30.5 months (range, 12-54 months).
      Changes in the choroidal circulation were always confined within the treatment
      margins (except in one case) and characterized by occlusion of choriocapillaris
      (100%), patent medium and/or large choroidal vessels (76%), retinochoroidal
      anastomosis (11%), and progressive choroidal vascular remodeling (42%). Forty-one
      cases (91%) showed persistent clinical regression, and four cases (9%) recurred;
      recurrent cases showed retinochoroidal anastomosis. CONCLUSIONS: Transpupillary
      thermotherapy is suggested as a new single therapeutic modality in the treatment
      of selected choroidal melanomas, but more precise eligibility criteria and longer
      follow-up are mandatory. Patent choroidal circulation, choroidal vascular
      remodeling, and anastomosis after transpupillary thermotherapy might be helpful
      to detect recurrent tumors.

PMID- 14597534
TI  - Iodine brachytherapy as an alternative to enucleation for large uveal melanomas.
AB  - PURPOSE: To evaluate the safety and efficacy of iodine 125 plaque brachytherapy
      (IBT) for large uveal melanomas. DESIGN: Retrospective, nonrandomized comparative
      trial (historical control). PARTICIPANTS: One hundred twenty-one consecutive
      patients with a large uveal melanoma according to the Collaborative Ocular
      Melanoma Study (COMS) criteria who attended a national ocular oncology service.
      METHODS: Ninety-seven patients (80%) underwent primary IBT (mean dose to tumor
      apex, 87 Gy) with noncollimated 20- to 25-mm plaques. Assessment of metastatic
      disease at death and visual outcome followed COMS guidelines. Time to low vision
      (20/70 or worse) and blindness (loss of 20/400 vision) in the study eye were
      modeled by Cox proportional hazards regression, based on both single- and
      repeated-failure data sets. Person-years of retained vision were calculated. MAIN
      OUTCOME MEASURES: All-cause and melanoma-specific survival, local and distant
      recurrence, and preservation of vision and cosmesis. RESULTS: Median tumor height
      was 10.7 mm (range, 4.5-16.8 mm), and largest basal tumor diameter was 16.1 mm
      (range, 7.3-25.0 mm). The Kaplan-Meier estimate for all-cause and melanoma
      specific survival was 62% (95% confidence interval [CI], 49%-72%) and 65% (95%
      CI, 52%-75%) at 5 years. The corresponding estimate for local tumor recurrence
      was 6% (95% CI, 2%-14%) and for major cosmetic abnormality was 38% (95% CI, 26%
      52%). The median visual acuity in the study eye was 20/100 at baseline and
      20/1600 at 2 years after treatment. The Kaplan-Meier estimate for avoiding low
      vision and blindness was 11% (95% CI, 4%-24%) and 26% (95% CI, 16%-37%) at 2
      years, respectively. Tumor height and location entirely posterior to the ora
      serrata were the most robust predictors of visual loss. In this series, 49 person
      years without low vision (median, 0.6 years; range, 0.04-8.2 years) and 111
      person-years without blindness (median, 1.0 years; range, 0.03-8.6 years) in the
      treated eye were conserved. CONCLUSIONS: Iodine 125 plaque brachytherapy seems to
      be a safe and effective alternative to enucleation with regard to survival and
      local tumor control. It provides a fair chance of preserving the eye with
      acceptable cosmesis and a reasonable chance of conserving useful vision for 1 to
      2 years.

PMID- 14597535
TI  - Transscleral resection versus iodine brachytherapy for choroidal malignant
      melanomas 6 millimeters or more in thickness: a matched case-control study.
AB  - OBJECTIVE: To assess differences in treatment outcome after transscleral
      resection (TSR) and iodine brachytherapy (IBT) of choroidal melanomas too thick
      for ruthenium brachytherapy. DESIGN: Matched case-control study. SETTING: Two
      national ocular oncology services. PARTICIPANTS: Forty-nine pairs of patients
      with choroidal melanoma 6 mm thick or more (range = 6-14), treated within 3 years
      of each other by either TSR or IBT, and retrospectively matched by age, visual
      acuity at diagnosis, largest basal tumor diameter, and posterior extension of the
      tumor. INTERVENTION: Iodine brachytherapy in Finland or TSR in United Kingdom.
      Prospectively collected time-to-event data were compared with parametric Weibull
      regression, adjusting for matching. MAIN OUTCOME MEASURES: Tumor control,
      complications, and visual acuity. RESULTS: Risk of local recurrence after IBT was
      smaller than that after TSR (hazard ratio [HR] = 0.02, 95% confidence interval
      [CI] = 0.01-0.11, P<0.001, Weibull regression adjusted for matching), but the 8
      year all-cause and melanoma-specific (HR = 0.81, 95% CI = 0.30-2.22, P = 0.69)
      survivals did not differ. The risks of cataract (HR = 2.05, 95% CI = 1.08-3.89, P
      = 0.029), maculopathy (HR = 2.28, 95% CI = 0.96-5.43, P = 0.062), and vitreous
      hemorrhage (HR = 2.30, 95% CI = 0.95-5.57, P = 0.064) were higher after IBT.
      Rubeosis, neovascular glaucoma, and optic neuropathy developed only after IBT.
      Risk of retinal detachment, exudative after IBT and rhegmatogenous after TSR (HR
      = 0.84, 95% CI = 0.40-1.75, P = 0.63), and risk of losing 20/60 vision (HR =
      1.37, 95% CI 0.76-2.45, P = 0.29) were comparable between the groups, but risk of
      losing 20/200 vision was higher after IBT (HR = 2.38, 95% CI = 1.48-3.83,
      P<0.001). No overall difference in quality of life was found. CONCLUSIONS: This
      study suggests that TSR preserves 20/200 vision better than IBT and avoids some
      of its major complications, but increases the risk of local recurrence. About 350
      patients would need to be randomized to prove that TRS preserves 20/60 vision
      better than IBT.

PMID- 14597536
TI  - Metastatic melanoma in the eye and orbit.
AB  - OBJECTIVE: Presentation of a large series of patients with metastatic melanoma
      involving the eye and orbit. DESIGN: Retrospective clinical study. PARTICIPANTS:
      Thirteen cases of metastatic melanoma involving intraocular tissues, 6 cases of
      metastatic melanoma in the orbit, and 1 case of metastatic melanoma involving
      both the eye and the orbit, treated in Lausanne between 1986 and 2002, were
      identified from the computer files of the ocular oncology and orbitopalpebral
      surgery units of Jules Gonin Hospital. METHODS: The analysis is based on the
      demographic data concerning these patients, clinical data concerning the tumor,
      the treatment applied, the outcome, and the follow-up. MAIN OUTCOME MEASURES:
      Clinical presentation of intraocular and orbital metastasis, interval between
      primary tumor and ocular metastasis, survival of the patients, evaluation of
      various therapeutic protocols. RESULTS: Intraocular metastases (14 cases, 15
      eyes) were situated in the choroid in 11 cases (isolated lesion, 6 cases;
      multiple lesions, 3 cases; diffuse involvement, 2 cases), in the iris and ciliary
      body in 2 cases, and in the retina and vitreous in 2 other cases. The primary
      tumor was a cutaneous melanoma in 8 cases, a melanoma of the contralateral eye in
      3 cases, a mucosal melanoma in 1 case, and was unknown in 2 cases. The mean
      interval between the diagnosis of ocular metastases and the patient's death was
      8.8 months (range, 1-48 months). The primary tumor in the 7 cases of orbital
      metastases was a cutaneous melanoma in 5 cases, a uveal melanoma in the
      contralateral eye in 1 case, and was unknown in 1 case. The mean interval between
      the diagnosis of orbital metastases and death was 19.7 months (range, 5-48
      months). The patients were treated by various protocols. The best results, in
      terms of both local tumor control and preservation of visual function, were
      obtained with circumscribed proton beam radiotherapy or external beam
      irradiation, depending on the site and extent of the tumor. CONCLUSIONS:
      Metastatic melanomas to the eye and orbit are rare and generally occur in
      patients with disseminated metastases during the terminal stages of the disease,
      with a short life expectancy. Treatment is palliative and, among the various
      possible treatment options, circumscribed proton beam radiotherapy or global
      photon beam radiotherapy, at relatively high irradiation doses, seems to achieve
      the most favorable results.

PMID- 14597538
TI  - Mitomycin C and pterygium excision.

PMID- 14597539
TI  - Headache syndrome.

PMID- 14597540
TI  - Tracker-assisted LASIK.

PMID- 14597542
TI  - Viscocanalostomy versus trabeculectomy.

PMID- 14597543
TI  - Management of acute elevation of IOP.

PMID- 14597544
TI  - Inverted pneumatic retinopexy.

PMID- 14597545
TI  - Inverted pneumatic retinopexy.

PMID- 14597547
TI  - Subconjunctival botulinum toxin injection.

PMID- 14597548
TI  - RPE translocation in ARMD.

PMID- 14597549
TI  - Unilateral temporal artery biopsy.

PMID- 14597551
TI  - Subconjunctival botulinum toxin injection.

PMID- 14597552
TI  - A continuous delivery system of IL-1 receptor antagonist reduces angiogenesis and
      inhibits tumor development.
AB  - The involvement of interleukin-1 (IL-1) in inflammation, tumor growth, and
      metastasis makes it an attractive target for therapeutic intervention. Here, we
      show that a continuous delivery of a low, but steady-state level of the naturally
      occurring IL-1 receptor antagonist (IL-1Ra) reduced inflammatory responses and
      inhibited tumor development in mice, phenomena that are induced by IL-1, mainly
      secretable IL-1beta. The IL-1Ra was delivered from microencapsulated genetically
      engineered cells, which overexpress and secrete this mediator. For a tumor model,
      we used fibrosarcoma cell line, which secretes high levels of IL-1beta; when
      injected s.c. into mice, the cells developed into large tumors characterized by
      very active angiogenic patterns. The proangiogenic features of IL-1beta were
      manifested at low levels of the cytokine, and release of 25 ng per day of the IL
      1Ra was needed to oppose its effects and inhibit tumor development. The
      continuous delivery of the IL-1Ra contributed to improved biocompatibility of the
      microencapsulated cell systems; the fibrotic sac surrounding the systems was much
      thinner with significantly less blood capillaries and inflammatory cells. Not
      only do our findings point to the antiangiogenic properties of IL-1Ra in
      inflammation and tumor growth, but they also provide a more efficient and
      convenient way for treating diseases involving IL-1.

PMID- 14597553
TI  - The metastasis suppressor gene C33/CD82/KAI1 induces apoptosis through reactive
      oxygen intermediates.
AB  - Here we describe the isolation of C33/CD82/KAI1 in a screen for apoptosis
      inducing genes. C33 is a gene that is downregulated in many metastatic tumor
      cells and the expression of which can attenuate the process of metastases
      formation in a variety of tumors. In accordance, we observed cell death induction
      by C33 in many different cell types. C33 seems to promote cell death by the
      generation of reactive oxygen intermediates (ROIs). These ROIs, however, are not
      derived from the mitochondrial respiratory chain as in most other scenarios
      leading to apoptosis. We observed that C33 renders cells sensitive to ROIs by
      causing the specific release of the intracellular antioxidant glutathione (GSH)
      from cells. Moreover, C33 activates the GTPase Cdc42, which mediates GSH release
      and apoptosis induction and allows to detect the formation of ROIs.

PMID- 14597554
TI  - Folate deficiency and ionizing radiation cause DNA breaks in primary human
      lymphocytes: a comparison.
AB  - DNA double-strand breaks, the most serious DNA lesion caused by ionizing
      radiation, are also caused by several vitamin or mineral deficiencies, such as
      for folate. Primary human lymphocytes were either irradiated or cultured at
      different levels of folate deficiency to assess cell proliferation, apoptosis,
      cell cycle, DNA breaks, and changes in gene expression. Both radiation and folate
      deficiency decreased cell proliferation and induced DNA breaks, apoptosis, and
      cell cycle arrest. Levels of folate deficiency commonly found resulted in effects
      similar to those caused by 1 Gy of radiation, a relatively high dose. Though both
      radiation and folate deficiency caused DNA breaks, they affected the expression
      of different genes. Radiation activated excision and DNA double-strand break
      repair genes and repressed mitochondrially encoded genes. Folate deficiency
      activated base and nucleotide excision repair genes and repressed folate-related
      genes. No DNA double-strand break repair gene was activated by folate deficiency.
      These findings suggest that a diet poor in folate may pose a risk of DNA damage
      comparable to that of a relatively high dose of radiation. Our results also
      suggest that research on biological effects of low-dose radiation should take
      into account the nutritional status of the subjects, because folate deficiency
      could confound the effects of low-dose radiation.

PMID- 14597555
TI  - COX-2-dependent stabilization of survivin in non-small cell lung cancer.
AB  - Elevated tumor cyclooxygenase 2 (COX-2) expression is associated with increased
      angiogenesis, tumor invasion and promotion of tumor cell resistance to apoptosis.
      The mechanism(s) by which COX-2 exerts its cytoprotective effects are not
      completely understood but may be due to an imbalance of pro- and anti-apoptotic
      gene expression. To analyze COX-2-dependent gene expression and apoptosis, we
      created cell lines constitutively expressing COX-2 cDNA in sense and antisense
      orientations. Whereas COX-2 sense cells have significantly heightened resistance
      to radiation and drug-induced apoptosis, COX-2 antisense cells are highly
      sensitive to apoptosis induction. We found that the expression of the anti
      apoptotic protein survivin correlated positively with COX-2 expression. A COX-2
      dependent modulation of survivin ubiquitination led to its stabilization in COX-2
      overexpressing cells, and this effect was replicated by exogenous PGE2 treatment
      of parental tumor cells. In contrast to previous studies in other cell types, in
      nonsmall cell lung cancer cells survivin was expressed in a cell cycle
      independent manner. When established in SCID mice in vivo, COX-2 antisense
      derived tumors had significantly decreased survivin levels while COX-2 sense
      derived tumors demonstrated elevated levels compared with controls. In accord
      with these findings, survivin and COX-2 were frequently upregulated and co
      expressed in human lung cancers in situ.

PMID- 14597556
TI  - The LPS receptor (CD14) links innate immunity with Alzheimer's disease.
AB  - To rapidly respond to invading microorganisms, humans call on their innate immune
      system. This occurs by microbe-detecting receptors, such as CD14, that activate
      immune cells to eliminate the pathogens. Here, we link the lipopolysaccharide
      receptor CD14 with Alzheimer's disease, a severe neurodegenerative disease
      resulting in dementia. We demonstrate that this key innate immunity receptor
      interacts with fibrils of Alzheimer amyloid peptide. Neutralization with
      antibodies against CD14 and genetic deficiency for this receptor significantly
      reduced amyloid peptide induced microglial activation and microglial toxicity.
      The observation of strongly enhanced microglial expression of the LPS receptor in
      brains of animal models of Alzheimer's disease indicates a clinical relevance of
      these findings. These data suggest that CD14 may significantly contribute to the
      overall neuroinflammatory response to amyloid peptide, highlighting the
      possibility that the enormous progress currently being made in the field of
      innate immunity could be extended to research on Alzheimer's disease.

PMID- 14597557
TI  - Polymers bearing sLex-mimetics are superior inhibitors of E-selectin-dependent
      leukocyte rolling in vivo.
AB  - Selectins mediate leukocyte rolling and may represent good anti-inflammatory drug
      targets. Detailed knowledge regarding the structure of selectin ligands has
      permitted development of selectin antagonists with varying specificities and
      activity. Efficacy of monovalent selectin antagonists may be increased by
      presenting them on a polymer backbone. We have synthesized a range of multivalent
      selectin antagonists and characterized their activity by using intravital
      microscopy of the mouse cremaster muscle. The monovalent inhibitor CGP77175A
      inhibited E-selectin-dependent leukocyte rolling at a dose of 3 mg/kg.
      Multivalent presentation of CGP77175A on a modified polylysine backbone (degree
      of polymerization = 1200; 50% of the polylysines carry the inhibitor) greatly
      enhanced in vivo activity giving an inhibitor that produced an equivalent effect
      at 0.1 mg/kg. The polylysine conjugate was also longer acting than the monovalent
      antagonist. In spite of greatly enhanced activity against E-selectin compared
      with monovalent inhibitor, the multivalent inhibitor had no measurable effect on
      P- or L-selectin-dependent leukocyte rolling.

PMID- 14597558
TI  - Melatonin-induced neuroprotection after closed head injury is associated with
      increased brain antioxidants and attenuated late-phase activation of NF-kappaB
      and AP-1.
AB  - Traumatic brain injury (TBI) is followed by massive production of reactive oxygen
      species (ROS), which mediate secondary cellular damage. Low molecular weight
      antioxidants (LMWA) constitute one of the defense mechanisms of the brain, and
      their levels correlate with post-TBI outcome. Melatonin, the main pineal hormone,
      possesses antioxidant properties. We investigated the effects of melatonin on
      neurobehavioral recovery, brain LMWA, and activation of the redox-sensitive
      transcription factors nuclear factor-kappaB (NF-kappaB) and AP-1 in mice
      subjected to closed head injury (CHI). Given 1 h after CHI, melatonin facilitated
      recovery during at least 1 wk (P<0.05) and decreased lesion size by approximately
      twofold (P<0.01). The dose response displayed a bell-shape, i.e., neuroprotection
      was achieved with 5 but not 1 or 10 mg/kg. At the neuroprotective dose, melatonin
      treatment was associated with sustained (4 days) elevation of brain LMWA,
      including ascorbic acid (P<0.05). In contrast, LMWA were unaffected by the
      administration of the neuroprotective endocannabinoid 2-arachidonoyl glycerol.
      Furthermore, melatonin did not alter early phase (24 h) CHI-induced activation of
      NF-kappaB and AP-1; however, it blocked the robust late-phase (8 days) activation
      of NF-kappaB and decreased that of AP-1 to below basal levels. Our results
      demonstrate that melatonin induces neuroprotection, presumably via potentiation
      of brain antioxidants and attenuation of NF-kappaB and AP-1 activation.

PMID- 14597559
TI  - Gene transcripts selectively down-regulated in the shell of the nucleus accumbens
      long after heroin self-administration are up-regulated in the core independent of
      response contingency.
AB  - Long-term drug-induced alterations in neurotransmission within the nucleus
      accumbens (NAc) shell and core may underlie relapse to drug-seeking behavior and
      drug-taking upon re-exposure to drugs and drug-associated stimuli (cues) during
      abstinence. Using an open screening strategy, we recently identified 25 gene
      transcripts, encoding for proteins involved in neuronal functioning and structure
      that are down-regulated in rat NAc shell after contingent (active), but not after
      non-contingent (passive), heroin administration. Studying the expression of the
      same transcripts in the NAc core by means of quantitative PCR, we now demonstrate
      that most of these transcripts are up-regulated in that NAc subregion long (3
      weeks) after heroin self-administration in rats. A similar up-regulation in gene
      expression was also apparent in the NAc core of animals with a history of non
      contingent heroin administration (yoked controls). These data indicate that
      heroin self-administration differentially regulates genes in the NAc core as
      compared with the shell. Moreover, whereas cognitive processes involved in active
      drug self-administration (e.g., instrumental learning) seems to direct gene
      expression in the NAc shell, neuroplasticity in the NAc core may be due to the
      pharmacological effects of heroin (including Pavlovian conditioning), as
      expressed in rats upon contingent as well as non-contingent administration of
      heroin.

PMID- 14597560
TI  - Free fatty acids trigger apoptosis and inhibit cell cycle progression in human
      vascular endothelial cells.
AB  - Plasma free fatty acid (FFA) concentrations are increased in states of insulin
      resistance and impair endothelial function. Because the underlying mechanisms are
      largely unknown, we examined selected, purified FFAs' (100-300 micromol/l, 24-48
      h) action on apoptosis, cell cycle distribution, and associated gene/protein
      expression in human umbilical vein endothelial cells (HUVECs). Stearic acid, but
      not oleic acid, time and concentration dependently increased endothelial
      apoptosis by fivefold (n=6, P<0.01), whereas polyunsaturated FFAs (PUFAs;
      linoleic, gamma-linolenic, and arachidonic acid) exerted proapoptotic activity
      only at 300 micromol/l (P<0.05). Proapoptotic FFA action increased with FFAs'
      number of double bonds and with protein expression of the apoptosis promotor bak.
      The G0/G1 cell cycle arrest (n=6, P<0.05) induced by stearic acid (+14%) and
      PUFAs (+30%) is reflected by up-regulation of p21(WAF-1/Cip1). In addition, all
      FFAs concentration dependently reduced (P<0.05) gene/protein expression of
      clusterin (-54%), NF-kappaB's inhibitor, IkappaBalpha (-50%), endothelin-1 (
      44%), and endothelial NO synthase (-44%). Plasma samples obtained from
      individuals with elevated plasma FFAs (372+/-22 micromol/l) increased endothelial
      apoptosis by 4.2-fold (P<0.001, n=10) compared with intra-individually matched
      low plasma FFA (56+/-21 micromol/l) conditions, underlining the results obtained
      by defined FFA stimulation. In conclusion, FFA structure differently affects
      endothelial cell proliferation and apoptosis, both representing key factors in
      the development of micro- and macrovascular dysfunction.

PMID- 14597561
TI  - Effects of Ca2+ sensing receptor activation in the growth plate.
AB  - The Ca2+-sensing receptor (CaR) is a G protein-coupled receptor expressed in many
      mammalian tissues, including the long bone's growth plate. CaR knockout mice
      exhibit growth retardation, suggesting that CaR may promote skeletal growth.
      However, the complex phenotype of these knockout mice, which includes
      hyperparathyroidism, hypercalcemia, and hypophosphatemia, may confound the
      effects of CaR activation. To determine whether CaR regulates growth plate
      chondrogenesis and longitudinal bone growth, we chose an organ culture model.
      Fetal rat metatarsal bones (dpc 20) were cultured in serum-free medium for 7 days
      in the presence or absence of NPS-R-568, a CaR agonist. The addition of 10 nM NPS
      R-568 increased the cumulative longitudinal growth of the metatarsal explants. To
      explore the underlying mechanisms, we then assessed the effects of NPS-R-568 on
      growth plate chondrocyte hypertrophy/differentiation and chondrocyte
      proliferation. After 7 days in culture, NPS-R-568 increased the height of the
      growth plate hypertrophic zone and the expression of collagen X, a marker of
      growth plate chondrocyte differentiation (assessed by immunohistochemistry). NPS
      R-568 also induced a significant increase of the height of the growth plate
      proliferative zone and of the total thymidine incorporation in the metatarsal
      bone. In conclusion, our findings suggest that the activation of CaR in the
      growth plate accelerates longitudinal bone growth by stimulating growth plate
      chondrogenesis.

PMID- 14597562
TI  - Ectopic expression of IGF-I and Shh by skeletal muscle inhibits disuse-mediated
      skeletal muscle atrophy and bone osteopenia in vivo.
AB  - The loss of normal weight-bearing activity, which occurs during bed rest, limb
      immobilization, and spaceflight, stimulates a catabolic response within the
      musculoskeletal system, which results in a loss of skeletal muscle mass and bone
      mineral. The mechanism by which loading of muscle and bone is sensed and
      translated into signals controlling tissue formation remains a major question in
      the field of musculoskeletal research. In this investigation, we have examined
      the ability of two potentially anti-atrophic proteins, IGF-I and Shh, to inhibit
      disuse atrophy within muscle and bone, when electroporated into skeletal muscle.
      We have found that electroporation and ectopic expression of IGF-I and/or Shh
      within the gastrocnemius/soleus muscle significantly stimulated muscle fiber
      hypertrophy and increases in muscle size. In addition, we report that
      electroporation and ectopic expression of IGF-I and/or Shh within the
      gastrocnemius/soleus muscle attenuated the lost of muscle fiber area, muscle
      mass, and muscle mass density that normally occurs during disuse muscle atrophy.
      Finally, we found that ectopic expression of IGF-I and Shh within the
      gastrocnemius/soleus muscle inhibits parameters of osteopenia within the tibia
      and fibula associated with hindlimb unloading. These results support the theory
      that skeletal muscle can regulate bone maintenance and could offer potentially
      novel and efficient therapeutic options for attenuating muscle and bone atrophy
      during aging, illness and spaceflight.

PMID- 14597563
TI  - Ischemia-induced phosphorylation of phospholemman directly activates rat cardiac
      Na/K-ATPase.
AB  - Regulation of the Na/K ATPase by protein kinases is model-specific. We have
      observed a profound activation of the sarcolemmal Na/K ATPase during cardiac
      ischemia, which is masked by an inhibitor of the enzyme in the cytosol. The aim
      of these studies was to characterize the pathways involved in this activation in
      the Langendorff-perfused rat heart. Na/K ATPase activity was determined by
      measuring ouabain-sensitive phosphate generation by cardiac homogenates at 37
      degrees C. In isolated sarcolemma, ischemia (30 min) caused a substantial
      activation of the Na/K ATPase compared with aerobic controls, which was abolished
      by perfusing the heart with staurosporine or H89. However, the alpha1 subunit of
      the Na/K ATPase was not phosphorylated during ischemia. The sarcolemmal protein
      phospholemman (PLM) was found associated with the Na/K ATPase alpha1 and beta1
      but not alpha2 subunits, and PLM increased its association with the catalytic
      subunit of PKA following ischemia. In vitro 14-3-3 binding assays indicated that
      PLM was phosphorylated following ischemia. These results indicate that the
      ischemia-induced activation of the Na/K ATPase is indirect, through
      phosphorylation of PLM, which is an integral part of the Na/K ATPase enzyme
      complex in the heart. The role of PLM is analogous to phospholamban in regulating
      the sarcoplasmic reticulum calcium ATPase.

PMID- 14597564
TI  - The neuropeptide Y Y1 receptor mediates NPY-induced inhibition of the gonadotrope
      axis under poor metabolic conditions.
AB  - Hypothalamic neuropeptide Y (NPY) plays a central role in the control of food
      intake, energy balance, and modulation of neuroendocrine functions. In
      particular, an increase in NPY expression participates in the inhibition of the
      reproductive activity under poor nutritional conditions. The present study was
      designed to evaluate further the involvement of the Y1 subtype of NPY receptors
      in these effects. Food intake, body weight gain, and the onset of puberty were
      studied in groups of wild-type and Y1 deficient mice that were either fed ad
      libitum or subjected to a 30% restriction in food intake. This moderate feeding
      restriction induced a similar deficit in body weight gain in wild-type and in Y1
      knockout mice. However, although wild-type mice experienced the expected delay of
      puberty, all mice in the food restriction group and lacking Y1 could go through
      puberty over the time of the experiment despite decreases in circulating leptin
      levels and increases in hypothalamic NPY expression. This observation
      demonstrates that the absence of Y1 impairs the perception of decreasing energy
      stores by the gonadotrope axis, demonstrating a physiological role for Y1 in the
      sensing of endogenous metabolic parameters by the hypothalamus.

PMID- 14597565
TI  - Regulation of TNF-alpha- and IFN-gamma-induced CXCL10 expression: participation
      of the airway smooth muscle in the pulmonary inflammatory response in chronic
      obstructive pulmonary disease.
AB  - The chemokine CXCL10 is produced by many inflammatory cells found in the diseased
      lung and has been implicated in the pathogenesis of chronic obstructive pulmonary
      disease (COPD). The present study demonstrates elevated CXCL10 protein in the
      lungs of COPD patients, which appears histologically in airway smooth muscle
      (hASM). In primary cultured hASM cells taken from normal donors, CXCL10 protein
      expression was induced by IFN-gamma and TNF-alpha, cytokines reported as elevated
      in COPD, and a synergistic response was obtained when they were combined. TNF
      alpha stimulation of hASM enhanced accumulation of CXCL10 mRNA, indicating
      regulation at the transcriptional level, while IFN-gamma stimulation resulted in
      a smaller accumulation of CXCL10 mRNA. When these cytokines were applied
      simultaneously, an additive effect was obtained. TNF-alpha-induced CXCL10
      expression in hASM was dependent on NFkappaB activation, and a salicylanilide
      NFkappaB inhibitor blocked the CXCL10 expression. In contrast, IFN-gamma
      stimulation resulted in transient NFkappaB activation, and the inhibitor had
      little effect on CXCL10 expression. When these cytokines were added
      simultaneously, NFkappaB was activated earlier and lasted longer, and the effect
      was blocked by the inhibitor. These data demonstrate a potential active role for
      hASM in pulmonary inflammatory diseases such as COPD by producing CXCL10.

PMID- 14597566
TI  - Helicobacter pylori stimulates host vascular endothelial growth factor-A (vegf-A)
      gene expression via MEK/ERK-dependent activation of Sp1 and Sp3.
AB  - VEGF-A is a key regulator of inflammatory and tumor-associated angiogenesis. H.
      pylori plays a critical role in the pathogenesis of benign and malignant gastric
      diseases. It has been suggested that H. pylori infection is associated with
      activation of host angiogenesis, however, underlying mechanisms as well as
      angiogenic growth factors activated by the bacterium have not yet been
      identified. Therefore, we investigated the influence of the bacterium on VEGF-A
      as a candidate host target gene in vivo and in vitro. We show that H. pylori
      potently up-regulates production and release of VEGF-A protein as well as vegf-A
      mRNA levels, and we provide strong evidence that enhanced recruitment of Sp1 and
      Sp3 transcription factors to two proximal GC-rich vegf-A promoter elements
      mediates H. pylori-triggered vegf-A gene expression. In addition, H. pylori
      infection increased the transactivating capacity of both Sp1 and Sp3, which
      suggests additional mechanism(s) of vegf-A gene regulation by the bacterium.
      Signaling studies identified the MEK>ERK1/-2 kinase cascade as principal host
      signaling pathway mediating H. pylori-stimulated vegf-A transcription. By
      identifying H. pylori as potent activator of vegf-A gene expression and
      characterization of underlying molecular mechanisms, our results provide novel
      insights into pathways linking the bacterium to host angiogenesis and may help to
      develop strategies to influence vegf-A gene expression in the setting of H.
      pylori infection.

PMID- 14597567
TI  - Innervated human corneal equivalents as in vitro models for nerve-target cell
      interactions.
AB  - A sensory nerve supply is crucial for optimal tissue function. However, the
      mechanisms for successful innervation and the signaling pathways between nerves
      and their target tissue are not fully understood. Engineered tissue substitutes
      can provide controllable environments in which to study tissue innervation. We
      have therefore engineered human corneal substitutes that promote nerve in-growth
      in a pattern similar to in vivo re-innervation. We demonstrate that these nerves
      (a) are morphologically equivalent to natural corneal nerves; (b) make
      appropriate contact with target cells; (c) can generate action potentials; (d)
      respond to chemical and physical stimuli; and (e) play an important role in the
      overall functioning of the bioengineered tissue. This model can be used for
      studying the more general topics of nerve ingrowth or regeneration and the
      interaction between nerves and their target cells and, more specifically, the
      role of nerves in corneal function. This model could also be used as an in vitro
      alternative to animals for safety and efficacy testing of chemicals and drugs.

PMID- 14597568
TI  - Characterization of cationic amino acid transporters and expression of
      endothelial nitric oxide synthase in human placental microvascular endothelial
      cells.
AB  - We investigated the expression and activity of arginine transporters and
      endothelial nitric oxide synthase (eNOS) in human placental microvascular
      endothelial cells (HPMEC). Using RT-PCR amplification products for eNOS, CAT1,
      CAT2A, CAT2B, CAT4, 4F2hc (CD98), rBAT and the light chains y+LAT1, y+LAT2, and
      b0+T1 were detected in HPMEC, but not B0+. Immunohistochemistry and Western
      blotting confirmed the presence of 4F2hc and CAT1 protein in HPMEC. 4F2hc-light
      chain dimers were indicated by a shift in molecular mass detected under
      nonreducing conditions. L-Arginine transport into HPMEC was independent of Na+ or
      Cl- and was inhibited by the neutral amino acid glutamine, but not by cystine.
      The Ki for glutamine inhibition was greater in the absence of Na+. Kinetic
      analysis supported a two-transporter model attributed to system y+L and system
      y+. Expression of eNOS in HPMEC was detectable by immunohistochemistry and ELISA
      but not by Western blotting. Activity of eNOS in HPMEC, measured over 48 h,
      either as the basal production of nitric oxide (NO) or as the accumulation of
      intracellular cGMP was not detectable. We conclude that HPMEC transport cationic
      amino acids by systems y+ and y+L and that basal eNOS expression and activity in
      these cells is low.

PMID- 14597569
TI  - The control of growth.
AB  - The growth of a cell or tissue involves complex interactions between genes,
      metabolism, nutrition and hormones. Until recently, separate lines of
      investigation have concentrated in isolated sections of each of the many
      independent levels of growth control; the interactions within and between the
      diverse pathways that affect growth and size at the cellular, tissue and
      organismal level were little understood. However, new insights into the control
      of growth are now emerging in the context of signalling, ageing, evolution,
      cancer and nutrition. In particular, it is becoming clear that the insulin
      signaling network is a key player that integrates not only metabolism and the
      response to nutrition, but also the regulation of cell death, ageing and
      longevity, as well as the regulation of growth and body size.

PMID- 14597570
TI  - Mechanisms of germ cell specification across the metazoans: epigenesis and
      preformation.
AB  - Germ cells play a unique role in gamete production, heredity and evolution.
      Therefore, to understand the mechanisms that specify germ cells is a central
      challenge in developmental and evolutionary biology. Data from model organisms
      show that germ cells can be specified either by maternally inherited determinants
      (preformation) or by inductive signals (epigenesis). Here we review existing data
      on 28 metazoan phyla, which indicate that although preformation is seen in most
      model organisms, it is actually the less prevalent mode of germ cell
      specification, and that epigenetic germ cell specification may be ancestral to
      the Metazoa.

PMID- 14597571
TI  - Distinct sites in E-cadherin regulate different steps in Drosophila tracheal tube
      fusion.
AB  - We have investigated how E-cadherin controls the elaboration of adherens junction
      associated cytoskeletal structures crucial for assembling tubular networks.
      During Drosophila development, tracheal branches are joined at branch tips
      through lumens that traverse doughnut-shaped fusion cells. Fusion cells form E
      cadherin contacts associated with a track that contains F-actin, microtubules,
      and Shot, a plakin that binds F-actin and microtubules. Live imaging reveals that
      fusion occurs as the fusion cell apical surfaces meet after invaginating along
      the track. Initial track assembly requires E-cadherin binding to beta-catenin.
      Surprisingly, E-cadherin also controls track maturation via a juxtamembrane site
      in the cytoplasmic domain. Fusion cells expressing an E-cadherin mutant in this
      site form incomplete tracks that contain F-actin and Shot, but lack microtubules.
      These results indicate that E-cadherin controls track initiation and maturation
      using distinct, evolutionarily conserved signals to F-actin and microtubules, and
      employs Shot to promote adherens junction-associated cytoskeletal assembly.

PMID- 14597572
TI  - Replicated anterior zeugopod (raz): a polydactylous mouse mutant with lowered Shh
      signaling in the limb bud.
AB  - A unique limb phenotype is described in a radiation-induced mutant mouse
      resulting from an inversion of a proximal segment of chromosome 5. The limb
      phenotype in the homozygous mutant presents with two anterior skeletal elements
      in the zeugopod but no posterior bone, hence the name replicated anterior
      zeugopod, raz. The zeugopod phenotype is accompanied by symmetrical central
      polydactyly of hand and foot. The chromosomal inversion includes the Shh gene and
      the regulatory locus, located approximately 1 Mb away, within the Lmbr1 gene. In
      homozygous mutants, the expression of Shh mRNA and Shh protein is severely
      downregulated to about 20% of wild-type limb buds, but Shh expression appears
      normal throughout the remainder of the embryo. Correspondingly, Gli3 expression
      is upregulated and posteriorly expanded in the raz/raz limb bud. We propose that
      the double anterior zeugopod and symmetrical central polydactyly are due to an
      increased and uniform concentration of the Gli3 repressor form because of lowered
      Shh signaling.

PMID- 14597573
TI  - Regulation of storage protein gene expression in Arabidopsis.
AB  - The expression of seed storage proteins is under tight developmental regulation
      and represents a powerful model system to study the regulation of gene expression
      during plant development. In this study, we show that three homologous B3 type
      transcription factors regulate the model storage protein gene, At2S3, via two
      distinct mechanisms: FUSCA3 (FUS3) and LEAFY COTYLEDON2 (LEC2) activate the At2S3
      promoter in yeast suggesting that they regulate At2S3 by directly binding its
      promoter; ABSCISIC ACID INSENSITIVE3 (ABI3), however, appears to act more
      indirectly on At2S3, possibly as a cofactor in an activation complex. In
      accordance with this, FUS3 and LEC2 were found to act in a partially redundant
      manner and differently from ABI3 in planta: At2S3 expression is reduced to
      variable and sometimes only moderate extent in fus3 and lec2 single mutants but
      is completely abolished in the lec2 fus3 double mutant. In addition, we found
      that FUS3 and LEC2 expression patterns, together with an unsuspected regulation
      of FUS3 by LEC2, enable us to explain the intriguing expression pattern of At2S3
      in lec2 or fus3 single mutants. Based on these results, we present a model of
      At2S3 regulation and discuss its implications for other aspects of seed
      maturation.

PMID- 14597574
TI  - Cct1, a phosphatidylcholine biosynthesis enzyme, is required for Drosophila
      oogenesis and ovarian morphogenesis.
AB  - Patterning of the Drosophila egg requires cooperation between the germline cells
      and surrounding somatic follicle cells. In order to identify genes involved in
      follicle cell patterning, we analyzed enhancer trap lines expressed in specific
      subsets of follicle cells. Through this analysis, we have identified tandem
      Drosophila genes homologous to CTP: phosphocholine cytidylyltransferase (CCT),
      the second of three enzymes in the CDP-choline pathway, which is used to
      synthesize phosphatidylcholine. Drosophila Cct1 is expressed at high levels in
      three specific subsets of follicle cells, and this expression is regulated, at
      least in part, by the TGF-beta and Egfr signaling pathways. Mutations in Cct1
      result in a number of defects, including a loss of germline stem cell
      maintenance, mispositioning of the oocyte, and a shortened operculum, suggesting
      that Cct1 plays multiple roles during oogenesis. In addition, Cct1 mutants
      display a novel branched ovariole phenotype, demonstrating a requirement for this
      gene during ovarian morphogenesis. These data provide the first evidence for a
      specific role for CCT, and thus for phosphatidylcholine, in patterning during
      development.

PMID- 14597575
TI  - Functional Notch signaling is required for BMP4-induced inhibition of myogenic
      differentiation.
AB  - The bone morphogenetic protein (BMP) and Notch signaling pathways are crucial for
      cellular differentiation. In many cases, the two pathways act similarly; for
      example, to inhibit myogenic differentiation. It is not known whether this
      inhibition is caused by distinct mechanisms or by an interplay between Notch and
      BMP signaling. Here we demonstrate that functional Notch signaling is required
      for BMP4-mediated block of differentiation of muscle stem cells, i.e. satellite
      cells and the myogenic cell line C2C12. Addition of BMP4 during induction of
      differentiation dramatically reduced the number of differentiated satellite and
      C2C12 cells. Differentiation was substantially restored in BMP4-treated cultures
      by blocking Notch signaling using either the gamma-secretase inhibitor L-685,458
      or by introduction of a dominant-negative version of the Notch signal mediator
      CSL. BMP4 addition to C2C12 cells increased transcription of two immediate Notch
      responsive genes, Hes1 and Hey1, an effect that was abrogated by L-685,458. A 3
      kb Hey1-promoter reporter construct was synergistically activated by the Notch 1
      intracellular domain (Notch 1 ICD) and BMP4. The BMP4 mediator SMAD1 mimicked BMP
      activation of the Hey1 promoter. A synthetic Notch-responsive promoter containing
      no SMAD1 binding sites responded to SMAD1, indicating that DNA-binding activity
      of SMAD1 is not required for activation. Accordingly, Notch 1 ICD and SMAD1
      interacted in binding experiments in vitro. Thus, the data presented here provide
      evidence for a direct interaction between the Notch and BMP signaling pathways,
      and indicate that Notch has a crucial role in the execution of certain aspects of
      BMP-mediated differentiation control.

PMID- 14597576
TI  - A positive role for Patched in Hedgehog signaling revealed by the intracellular
      trafficking of Sex-lethal, the Drosophila sex determination master switch.
AB  - The sex determination master switch, Sex-lethal (Sxl), controls sexual
      development as a splicing and translational regulator. Hedgehog (Hh) is a
      secreted protein that specifies cell fate during development. We show that Sxl is
      in a complex that contains all of the known Hh cytoplasmic components, including
      Cubitus interruptus (Ci) the only known target of Hh signaling. Hh promotes the
      entry of Sxl into the nucleus in the wing disc. In the anterior compartment, the
      Hh receptor Patched (Ptc) is required for this effect, revealing Ptc as a
      positive effector of Hh. Some of the downstream components of the Hh signaling
      pathway also alter the rate of Sxl nuclear entry. Mutations in Suppressor of
      Fused or Fused with altered ability to anchor Ci are also impaired in anchoring
      Sxl in the cytoplasm. The levels, and consequently, the ability of Sxl to
      translationally repress downstream targets in the sex determination pathway, can
      also be adversely affected by mutations in Hh signaling genes. Conversely,
      overexpression of Sxl in the domain that Hh patterns negatively affects wing
      patterning. These data suggest that the Hh pathway impacts on the sex
      determination process and vice versa and that the pathway may serve more
      functions than the regulation of Ci.

PMID- 14597577
TI  - Msx2 and Twist cooperatively control the development of the neural crest-derived
      skeletogenic mesenchyme of the murine skull vault.
AB  - The flat bones of the vertebrate skull vault develop from two migratory
      mesenchymal cell populations, the cranial neural crest and paraxial mesoderm. At
      the onset of skull vault development, these mesenchymal cells emigrate from their
      sites of origin to positions between the ectoderm and the developing cerebral
      hemispheres. There they combine, proliferate and differentiate along an
      osteogenic pathway. Anomalies in skull vault development are relatively common in
      humans. One such anomaly is familial calvarial foramina, persistent unossified
      areas within the skull vault. Mutations in MSX2 and TWIST are known to cause
      calvarial foramina in humans. Little is known of the cellular and developmental
      processes underlying this defect. Neither is it known whether MSX2 and TWIST
      function in the same or distinct pathways. We trace the origin of the calvarial
      foramen defect in Msx2 mutant mice to a group of skeletogenic mesenchyme cells
      that compose the frontal bone rudiment. We show that this cell population is
      reduced not because of apoptosis or deficient migration of neural crest-derived
      precursor cells, but because of defects in its differentiation and proliferation.
      We demonstrate, in addition, that heterozygous loss of Twist function causes a
      foramen in the skull vault similar to that caused by loss of Msx2 function. Both
      the quantity and proliferation of the frontal bone skeletogenic mesenchyme are
      reduced in Msx2-Twist double mutants compared with individual mutants. Thus Msx2
      and Twist cooperate in the control of the differentiation and proliferation of
      skeletogenic mesenchyme. Molecular epistasis analysis suggests that Msx2 and
      Twist do not act in tandem to control osteoblast differentiation, but function at
      the same epistatic level.

PMID- 14597578
TI  - Squamous cell carcinoma and mammary abscess formation through squamous metaplasia
      in Smad4/Dpc4 conditional knockout mice.
AB  - Smad4 is a central mediator for TGFbeta signals, which play important functions
      in many biological processes. To study the role of Smad4 in mammary gland
      development and neoplasia, we disrupted this gene in mammary epithelium using a
      Cre-loxP approach. Smad4 is expressed in the mammary gland throughout
      development; however, its inactivation did not cause abnormal development of the
      gland during the first three pregnancies. Instead, lack of Smad4 gradually
      induced cell proliferation, alveolar hyperplasia and transdifferentiation of
      mammary epithelial cells into squamous epithelial cells. Consequently, all mutant
      mice developed squamous cell carcinoma and/or mammary abscesses between 5 and 16
      months of age. We demonstrated that absence of Smad4 resulted in beta-catenin
      accumulation at onset and throughout the process of transdifferentiation,
      implicating beta-catenin, a key component of the Wnt signaling pathway, in the
      development of squamous metaplasia in Smad4-null mammary glands. We further
      demonstrated that TGFbeta1 treatment degraded beta-catenin and induced epithelial
      mesenchymal transformation in cultured mammary epithelial cells. However, such
      actions were blocked in the absence of Smad4. These findings indicate that
      TGFbeta/Smad4 signals play a role in cell fate maintenance during mammary gland
      development and neoplasia.

PMID- 14597579
TI  - Physiology and pathophysiology of vascular signaling controlled by guanosine
      3',5'-cyclic monophosphate-dependent protein kinase [corrected].

PMID- 14597580
TI  - Endothelin receptor blockers in cardiovascular disease.
AB  - The endothelin (ET) system is comprised of 4 active ETs, with ET-1 being the
      predominant isoform in the cardiovascular system. Because of the potent
      vasoconstricting and mitogenic effects of ET-1 and its involvement in various
      cardiovascular diseases, blockade of the ET receptor has received considerable
      attention. ET receptor antagonism has been demonstrated to be beneficial in
      patients with pulmonary hypertension. The nonselective ET receptor antagonist
      bosentan improves exercise capacity and increases time to clinical worsening in
      patients with pulmonary arterial hypertension. The selective ET A receptor
      antagonist sitaxsentan also improves hemodynamics and exercise capacity in
      patients with pulmonary arterial hypertension. Results with ET receptor
      antagonists in congestive heart failure have been disappointing. Although some
      studies have suggested benefit, larger studies have been neutral. The use of ET
      receptor antagonists for other conditions has not been fully explored. Future
      studies with the use of ET receptor antagonists as part of a multidrug regimen
      are also needed.

PMID- 14597581
TI  - Cardiac biomarkers for risk stratification of patients with acute pulmonary
      embolism.

PMID- 14597582
TI  - Images in cardiovascular medicine. Multiple ruptured plaques: serial
      intravascular ultrasound examinations.

PMID- 14597583
TI  - The plunger, fine tuned.

PMID- 14597584
TI  - Anticoagulants (thrombin inhibitors) and aspirin synergize with P2Y12 receptor
      antagonism in thrombosis.
AB  - BACKGROUND: This study was designed to determine whether (1) P2Y12 antagonism
      synergizes with other antithrombotics and (2) anticoagulants (thrombin
      inhibitors) affect the antithrombotic activity elicited by P2Y12 antagonism.
      METHODS AND RESULTS: Thrombosis was achieved by perfusion of human and murine
      blood through type III collagen-coated capillaries at arterial shear rate.
      CT50547, a direct-acting P2Y12 antagonist, inhibited thrombosis in PPACK- but not
      heparin-anticoagulated human blood. In contrast, CT50547 inhibited thrombosis in
      aspirin-treated individuals independently of the anticoagulant. Thrombin and TXA2
      also synergized with P2Y12 in the absence of anticoagulation, because combined
      treatment of aspirin or C921-78 (a factor Xa inhibitor) with CT50547 or 2-MeSAMP
      (a P2Y12 antagonist) inhibited the thrombotic process, whereas all treatments
      failed to inhibit thrombosis when used individually. Synergism was also observed
      ex vivo when P2Y12-deficient (P2Y12-/-) mice were administered aspirin or
      coagulation inhibitors (C921-78 and bivalirudin). Finally, using intravital
      microscopy, we found that both C921-78 and bivalirudin abrogated the thrombotic
      process in P2Y12+/- mice, whereas each showed only partial efficacy in P2Y12+/+
      animals. CONCLUSIONS: Our study indicates that (1) thrombin inhibitors and
      aspirin have a demonstrable synergy of antithrombotic activity with P2Y12
      antagonism and (2) the in vitro analysis of the antithrombotic activity of P2Y12
      antagonists is affected by the anticoagulant used for blood collection. This
      suggests that the antithrombotic potential of P2Y12 antagonists in vitro may be
      overestimated in anticoagulated samples of blood and best achieved in vivo by the
      inclusion of aspirin and/or a thrombin inhibitor.

PMID- 14597585
TI  - Control of skin sympathetic nerve activity during intermittent static handgrip
      exercise.
AB  - BACKGROUND: Exercise activates the sympathetic nervous system as a function of
      the type and intensity of exercise and of the target organ studied. Although
      central command and activity of metabolically sensitive afferents from exercising
      muscle are the principal determinants of sympathetic outflow directed to skeletal
      muscle, the mechanisms that govern sympathetic outflow directed to skin are less
      clear. METHODS AND RESULTS: We measured skin sympathetic nerve activity (SSNA)
      during intermittent static handgrip (SHG; at 45% of maximal voluntary
      contraction; four 5-second contractions per minute for 3 minutes), during
      unrestricted forearm perfusion (control), during stimulation of forearm
      mechanoreceptors with venous congestion, and during ischemia produced by forearm
      circulatory arrest. Under all 3 conditions, SSNA increased within 1 to 2 seconds
      of the onset of handgrip. During ischemia but not during venous congestion, SSNA
      increased more compared with control (P<0.05) and remained elevated when forearm
      ischemia was maintained after handgrip exercise (posthandgrip circulatory
      arrest). In addition, simulated handgrip and intermittent forearm compression
      produced by a pneumatic cuff also evoked brief increases of SSNA. CONCLUSIONS: In
      addition to central neural factors, afferent input from exercising muscle plays
      an important role in modulating sympathetic outflow directed to skin.

PMID- 14597586
TI  - Isolation and transplantation of autologous circulating endothelial cells into
      denuded vessels and prosthetic grafts: implications for cell-based vascular
      therapy.
AB  - BACKGROUND: Blood-borne endothelial cells originating from adult bone marrow were
      reported previously. These cells have the properties of an endothelial progenitor
      cell (EPC) and can be mobilized by cytokines and recruited to sites of
      neovascularization, where they differentiate into mature endothelial cells.
      Current protocols for isolation of EPCs from peripheral blood rely on enrichment
      and selection of CD34+ mononuclear cells. METHODS AND RESULTS: In this report, we
      describe a streamlined method for the isolation and expansion of EPCs from
      peripheral blood and evaluate their therapeutic potential for autologous cell
      based therapy of injured blood vessels and prosthetic grafts. A subset of
      unfractionated mononuclear cells exhibited the potential to differentiate in
      vitro into endothelial cells under selective growth conditions. The cells were
      efficiently transduced ex vivo by a retroviral vector expressing the LacZ
      reporter gene and could be expanded to yield sufficient numbers for therapeutic
      applications. Transplantation of these cells into balloon-injured carotid
      arteries and into bioprosthetic grafts in rabbits led to rapid endothelialization
      of the denuded vessels and graft segments, resulting in significant reduction in
      neointima deposition. CONCLUSIONS: We conclude that transplantation of EPCs may
      play a crucial role in reestablishing endothelial integrity in injured vessels,
      thereby inhibiting neointimal hyperplasia. These findings may have implications
      for novel and practical cell-based therapies for vascular disease.

PMID- 14597587
TI  - Myocardial contractile reserve by dobutamine stress echocardiography predicts
      improvement in ejection fraction with beta-blockade in patients with heart
      failure: the Beta-Blocker Evaluation of Survival Trial (BEST).
AB  - BACKGROUND: beta-Blockers improve survival and reduce hospitalization in chronic
      heart failure (CHF) by biologically improving left ventricular ejection fraction
      (LVEF). However, a good predictor of improvement with this therapy has not been
      identified. This substudy of BEST examined whether myocardial contractile
      reserve, as determined by dobutamine stress echocardiography, predicts
      improvement in LVEF. METHODS AND RESULTS: Seventy-nine patients with class III/IV
      CHF underwent dobutamine stress echocardiography before treatment with bucindolol
      (n=41) or placebo (n=38). Regional wall motion score index (WMSI) was calculated
      as the sum of the scores in each segment divided by the total number of segments
      visualized. WMSI was compared with change in LVEF after 3 months of therapy as
      determined by gated radionuclide scan. Change in WMSI correlated inversely with
      change in LVEF after 3 months of bucindolol (r=-0.72, P<0.0001) and was the most
      significant multivariate predictor of change in LVEF (P=0.0002). Patients with
      contractile reserve had demographics similar to those of patients without
      contractile reserve, including RVEF, LVEF, systolic blood pressure, and CHF
      duration. However, patients without contractile reserve had higher baseline
      plasma norepinephrine levels (687+/-333 versus 420+/-246 pg/mL, P<0.05) and
      greater decrease in plasma norepinephrine in response to bucindolol (-249+/-171
      versus -35+/-277 pg/mL, P<0.05). CONCLUSIONS: This study suggests a direct
      relationship between contractile reserve and improvement in LVEF with beta
      blocker therapy in patients with advanced CHF. Patients without contractile
      reserve have higher resting adrenergic drive, as reflected by plasma
      norepinephrine, and may experience greater sympatholytic effects from bucindolol.

PMID- 14597588
TI  - Effect of posture on blood and intraocular pressures in multiple system atrophy,
      pure autonomic failure, and baroreflex failure.
AB  - BACKGROUND: Intraocular pressure (IOP) may be partially under systemic vascular
      control. This study examined whether a correlation exists between blood and
      intraocular pressures in patients with autonomic dysfunction. METHODS AND
      RESULTS: Eleven patients with 3 types of confirmed autonomic dysfunction
      (multiple system atrophy, pure autonomic failure, and baroreflex failure) were
      compared with age- and gender-matched controls and had IOP, systolic blood
      pressure, diastolic blood pressure, heart rates, and calculated mean arterial
      pressures (MAP) and mean ocular perfusion pressures (MOPP) measured in the
      supine, sitting, and standing positions. Data were analyzed with a general linear
      model repeated-measures ANOVA. All pressures for patients showed a dramatic
      decline (P<0.001) from supine to standing (MAP -31+/-14 mm Hg; IOP -6+/-3 mm Hg;
      MOPP -25+/-14 mm Hg) compared with controls (MAP +4+/-7 mm Hg; IOP -1+/-2 mm Hg;
      MOPP +6+/-7 mm Hg). There was no significant change in heart rate from supine to
      standing for patients compared with controls (P=0.648). Within both the multiple
      system atrophy (n=5) and pure autonomic failure (n=4) groups, all initial
      pressures were similar to control pressures in the supine position, whereas
      patients with baroreflex failure (n=2) had higher mean pressures than respective
      controls in the supine position. CONCLUSIONS: In autonomic dysfunction, a large
      decrease in MAP correlated with a large decrease in IOP. These data suggest that
      the autonomic nervous system, perhaps through an influence on systemic blood
      pressure, has a significant role in IOP regulation.

PMID- 14597589
TI  - Women's early warning symptoms of acute myocardial infarction.
AB  - BACKGROUND: Data remain sparse on women's prodromal symptoms before acute
      myocardial infarction (AMI). This study describes prodromal and AMI symptoms in
      women. METHODS AND RESULTS: Participants were 515 women diagnosed with AMI from 5
      sites. Using the McSweeney Acute and Prodromal Myocardial Infarction Symptom
      Survey, we surveyed them 4 to 6 months after discharge, asking about symptoms,
      comorbidities, and demographic characteristics. Women were predominantly white
      (93%), high school educated (54.8%), and older (mean age, 66+/-12), with 95%
      (n=489) reporting prodromal symptoms. The most frequent prodromal symptoms
      experienced more than 1 month before AMI were unusual fatigue (70.7%), sleep
      disturbance (47.8%), and shortness of breath (42.1%). Only 29.7% reported chest
      discomfort, a hallmark symptom in men. The most frequent acute symptoms were
      shortness of breath (57.9%), weakness (54.8%), and fatigue (42.9%). Acute chest
      pain was absent in 43%. Women had more acute (mean, 7.3+/-4.8; range, 0 to 29)
      than prodromal (mean, 5.71+/-4.36; range, 0 to 25) symptoms. The average
      prodromal score, symptom weighted by frequency and intensity, was 58.5+/-52.7,
      whereas the average acute score, symptom weighted by intensity, was 16.5+/-12.1.
      These 2 scores were correlated (r=0.61, P<0.001). Women with more prodromal
      symptoms experienced more acute symptoms. After controlling for risk factors,
      prodromal scores accounted for 33.2% of acute symptomatology. CONCLUSIONS: Most
      women have prodromal symptoms before AMI. It remains unknown whether prodromal
      symptoms are predictive of future events.

PMID- 14597590
TI  - Sex differences in health status after coronary artery bypass surgery.
AB  - BACKGROUND: Although previous studies have shown functional improvements in
      patients who undergo coronary artery bypass graft (CABG) surgery, data are
      conflicting on whether the gains achieved by women are similar to or less than
      those achieved by men. METHODS AND RESULTS: We compared physical and
      psychological functional gains and readmission rates between 777 men and 295
      women who underwent first CABG consecutively between February 1999 and February
      2001. Physical function and mental health were measured by means of the Short
      Form 36-Item Health Survey (SF-36). At 6 months, both men and women showed, on
      average, a significant improvement in physical function and mental health, but
      men improved significantly more than women. After adjustment for baseline
      characteristics, the mean score improvement in women was half that of men for
      physical function (7.3 versus 14.0, P=0.0002) and 25% less than that of men for
      mental health (-3.0 versus 8.9, P=0.026). The absolute rates of adverse outcomes,
      such as hospital readmission, worsening functional status, and worsening mental
      health, were significantly higher in women (32.6%, 25.7%, and 17.5%,
      respectively) than in men (21.2%, 11.1%, and 12.6%, respectively) and remained
      significantly different in multivariable analysis. CONCLUSIONS: CABG surgery is
      associated with lower functional gains and higher readmission rates in women
      compared with men 6 months after operation.

PMID- 14597591
TI  - Hospitalization costs of primary stenting versus thrombolysis in acute myocardial
      infarction: cost analysis of the Canadian STAT Study.
AB  - BACKGROUND: We previously showed that primary stenting was more effective than
      accelerated tPA in reducing the 6-month composite of death, reinfarction, stroke,
      or repeat revascularization for ischemia. This study looks at the hospitalization
      costs of primary stenting compared with accelerated tPA. METHODS AND RESULTS:
      Initial and 6-month hospitalization costs were computed for all patients randomly
      assigned to primary stenting (n=62) or accelerated tPA (n=61) in the Stenting
      versus Thrombolysis in Acute myocardial infarction Trial (STAT). Costs and
      resource usage were collected in detail for each patient. Physician fees were
      obtained directly from billings to the Ontario Health Insurance Plan. The length
      of initial hospitalization was 6.7+/-11.3 days in the stent group and 8.7+/-6.7
      days in the tPA group (P<0.001). Total hospitalization days at 6 months were
      8.3+/-13 days in the stent group and 12.1+/-14.0 days in the tPA group (P=0.001).
      Hospitalization costs were less in the stent group for the initial
      hospitalization, 6354 dollars +/-6382 versus 7893 dollars +/-4429 (P=0.001), and
      at 6 months, 7100 dollars +/-7111 versus 9559 dollars +/-6933 (P=0.001).
      CONCLUSIONS: In centers in which facilities and experienced interventionists are
      available, primary stenting is less costly and more effective than thrombolysis.

PMID- 14597592
TI  - Stratification of pediatric heart failure on the basis of neurohormonal and
      cardiac autonomic nervous activities in patients with congenital heart disease.
AB  - BACKGROUND: Stratification of pediatric patients with congenital heart disease
      (CHD) has been based on their hemodynamics and/or functional capacity. Our
      purpose was to compare cardiac autonomic nervous activity (CANA) and
      neurohormonal activities (NHA) with postoperative status in stable CHD patients
      with biventricular physiology. METHODS AND RESULTS: We divided 379 subjects (297
      CHD patients, 28 dilated cardiomyopathy patient, and 54 control subjects) into 4
      subgroups according to New York Heart Association (NYHA) class (1.3+/-0.7) and
      measured various CANA and NHA indices. Stepwise decreases in baroreflex
      sensitivity (BRS), heart rate variability (HRV), adrenergic imaging, and vital
      capacity (VC) were observed in proportion to functional capacity in normal to
      NYHA II patients (P<0.001). However, there were no differences in these indices
      between NYHA II and III+IV groups, whereas a stepwise proportional increase in
      NHA indices was observed in these groups (P<0.001). Natriuretic peptides
      differentiated all NYHA classes. BRS, HRV, and VC were greater in the adult
      patients than in the child patients (P<0.05 to 0.01), although the functional
      class in adult patients was lower. Cardiac surgeries resulted in low BRS and VC,
      and the VC reduction independently determined a small HRV. Even if functional
      class and ejection fraction were comparable, CANA and brain natriuretic peptide
      were lower in CHD patients than in dilated cardiomyopathy patients (P<0.05 to
      0.001). CONCLUSIONS: CANA and NHA indices are useful to stratify mild and severe
      heart failure in stable postoperative CHD patients, respectively. However,
      careful attention should be paid to age- and surgery-related influences on these
      indices.

PMID- 14597593
TI  - Inhibition of delta-protein kinase C protects against reperfusion injury of the
      ischemic heart in vivo.
AB  - BACKGROUND: Current treatment for acute myocardial infarction (AMI) focuses on
      reestablishing blood flow (reperfusion). Paradoxically, reperfusion itself may
      cause additional injury to the heart. We previously found that delta-protein
      kinase C (deltaPKC) inhibition during simulated ischemia/reperfusion in isolated
      rat hearts is cardioprotective. We focus here on the role for deltaPKC during
      reperfusion only, using an in vivo porcine model of AMI. METHODS AND RESULTS: An
      intracoronary application of a selective deltaPKC inhibitor to the heart at the
      time of reperfusion reduced infarct size, improved cardiac function, inhibited
      troponin T release, and reduced apoptosis. Using 31P NMR in isolated perfused
      mouse hearts, we found a faster recovery of ATP levels in hearts treated with the
      deltaPKC inhibitor during reperfusion only. CONCLUSIONS: Reperfusion injury after
      cardiac ischemia is mediated, at least in part, by deltaPKC activation. This
      study suggests that including a deltaPKC inhibitor at reperfusion may improve the
      outcome for patients with AMI.

PMID- 14597594
TI  - Differential effects of selective cyclooxygenase-2 inhibitors on endothelial
      function in salt-induced hypertension.
AB  - BACKGROUND: In view of the ongoing controversy about potential differences in
      cardiovascular safety of selective cyclooxygenase (COX)-2 inhibitors (coxibs), we
      compared the effects of 2 different coxibs and a traditional NSAID on endothelial
      dysfunction, a well-established surrogate of cardiovascular disease, in salt
      induced hypertension. METHODS AND RESULTS: Salt-sensitive (DS) and salt-resistant
      (DR) Dahl rats were fed a high-sodium diet (4% NaCl) for 56 days. From days 35 to
      56, diclofenac (6 mg x kg(-1) x d(-1); DS-diclofenac), rofecoxib (2 mg x kg(-1) x
      d(-1); DS-rofecoxib), celecoxib (25 mg x kg(-1) x d(-1); DS-celecoxib) or placebo
      (DS-placebo) was added to the chow. Blood pressure increased with sodium diet in
      the DS groups, which was more pronounced after diclofenac and rofecoxib treatment
      (P<0.005 versus DS-placebo) but was slightly decreased by celecoxib (P<0.001
      versus DS-placebo). Sodium diet markedly reduced NO-mediated endothelium
      dependent relaxations to acetylcholine (10-10-10-5 mol/L) in aortic rings of
      untreated hypertensive rats (P<0.005 versus DR-placebo). Relaxation to
      acetylcholine improved after celecoxib (P<0.005 versus DS-placebo and DS
      rofecoxib) but remained unchanged after rofecoxib and diclofenac treatment.
      Vasoconstriction after nitric oxide synthase inhibition, indicating basal NO
      release, with N(omega)-nitro-L-arginine methyl ester (10-4 mol/L) was blunted in
      DS rats (P<0.05 versus DR-placebo), normalized by celecoxib, but not affected by
      rofecoxib or diclofenac. Indicators of oxidative stress, 8-isoprostane levels,
      were elevated in untreated DS rats on 4% NaCl (6.55+/-0.58 versus 3.65+/-1.05
      ng/mL, P<0.05) and normalized by celecoxib only (4.29+/-0.58 ng/mL). CONCLUSIONS:
      These data show that celecoxib but not rofecoxib or diclofenac improves
      endothelial dysfunction and reduces oxidative stress, thus pointing to
      differential effects of coxibs in salt-induced hypertension.

PMID- 14597595
TI  - ATP and UTP responses of cultured rat aortic smooth muscle cells revisited:
      dominance of P2Y2 receptors.
AB  - 1. It has previously been shown that ATP and UTP stimulate P2Y receptors in
      vascular smooth muscle cells (VSMCs), but the nature of these receptors, in
      particular the contribution of P2Y2 and P2Y4 subtypes, has not been firmly
      established. Here we undertake a further pharmacological analysis of [3H]inositol
      polyphosphate responses to nucleotides in cultured rat VSMCs. 2. ATP generated a
      response that was partial compared to UTP, as reported earlier. 3. In the
      presence of a creatine phosphokinase (CPK) system for regenerating nucleoside
      triphosphates, the response to ATP was increased, the response to UTP was
      unchanged, and the difference between UTP and ATP concentration-response curves
      disappeared. Chromatographic analysis showed that ATP was degraded slightly
      faster than UTP. 4. The response to UDP was always smaller than that to UTP, but
      with a shallow slope and a high potency component. In the presence of hexokinase
      (which prevents the accumulation of ATP/UTP from ADP/UDP), the maximum response
      to UDP was reduced and the high-potency component of the curve was retained. By
      contrast, the response to ADP was weaker throughout in the presence of
      hexokinase. 5. ATP gamma S was an effective agonist with a similar EC50 to UTP,
      but with a lower maximum. ITP was a weak agonist compared with UTP. 6. Suramin
      was an effective antagonist of the response to UTP (pA2=4.48), but not when ATP
      was the agonist. However, suramin was an effective antagonist (pA2=4.45) when
      stimulation with ATP was in the presence of the CPK regenerating system. 7. Taken
      together with the results of others, these findings indicate that the response of
      cultured rat VSMCs to UTP and to ATP is predominantly at the P2Y2 receptor, and
      that there is also a response to UDP at the P2Y6 receptor.

PMID- 14597596
TI  - Rabbit aortic endothelial dysfunction by low-density lipoprotein is attenuated by
      L-arginine, L-ascorbate and pyridoxine.
AB  - 1. We investigated the relative effectiveness of L-arginine, L-ascorbate and
      pyridoxine in preventing the impairment of endothelium-mediated vasorelaxation
      induced by native low-density lipoprotein (nLDL) from healthy subjects, oxidised
      LDL (oxLDL, formed by oxidation of nLDL) or nLDL from type II diabetic patients
      (dLDL). 2. Rabbit aortic rings were exposed to nLDL, dLDL or oxLDL (50-200 mg
      protein l-1), or corresponding vehicle, following which they were constricted
      with noradrenaline 10(-6) M; concentration-relaxation curves were determined to
      acetylcholine (ACh), A23187, or sodium nitroprusside (NP), in the absence or
      presence of L-arginine (10(-5)-10(-3) M), L-ascorbate (10(-5)-10(-3) M) and
      pyridoxine (0.5-2.0 mM). 3. nLDL, dLDL and oxLDL all inhibited relaxant responses
      to ACh and A23187, but not to NP, in a concentration-dependent manner
      (oxLDL>dLDL>nLDL). 4. In the presence of all LDL preparations, L-arginine, L
      ascorbate or pyridoxine each improved ACh and A23187 responses, although none
      completely normalised endothelium-dependent relaxations. The maximal effect of L
      arginine occurred at 10(-4) M. The combination of L-arginine 10(-4) M, L
      ascorbate 10(-5) M and pyridoxine 2.0 mM was equally effective as L-arginine 10(
      4) M alone. 5. Our results confirm that nLDL, dLDL and oxLDL exert inhibitory
      effects on endothelium dependent, but not endothelium independent, relaxation of
      rabbit aorta. ACh and A23187 responses in the presence of any LDL species can be
      ameliorated by supplementation with L-arginine, L-ascorbate or pyridoxine, either
      singly or in combination, with no agent or combination proving superior to L
      arginine alone. Nevertheless, ACh and A23187 responses are not completely
      normalised with such supplements, suggesting that there also exists a component
      of LDL-induced inhibition of endothelium-mediated vasorelaxation that is
      independent of the nitric oxide system.

PMID- 14597597
TI  - Hyper-reactivity of cerebral arteries from ovariectomized rats: therapeutic
      benefit of tamoxifen.
AB  - 1. An increased incidence of systemic hypertension has been documented in
      postmenopausal women and identified as an independent risk factor in the
      development of cerebrovascular stroke. The present study examined whether
      cerebrovascular reactivity was increased in the hypertensive ovariectomized rat,
      and explored the potential therapeutic benefit of the partial estrogen receptor
      agonist tamoxifen. 2. Female Sprague-Dawley rats were subjected to bilateral
      ovariectomy (OVX, n=16) or a sham operation (n=8). At 6-week postsurgery, rats
      were anesthetized to assess ventricular contractility and blood pressure. In a
      second series of experiments, OVX rats (n=8) were given tamoxifen starting 3
      weeks postsurgery, and continued for 3 weeks. At the end of each protocol, the
      middle cerebral artery was harvested and rings were mounted in wire-myographs to
      measure isometric tension. 3. Systolic arterial pressure (SAP) was significantly
      increased (P<0.05) in the OVX rat (174+/-8 mmHg), as compared to sham (135+/-6
      mmHg). The resting tension of isolated cerebral arteries from OVX rats (186+/-15
      mg) was significantly elevated (P<0.05), as compared to sham (129+/-9 mg).
      Phenylephrine treatment did not elicit a constriction of cerebral arteries
      isolated from sham rats, whereas a potent response (P<0.05) was observed in OVX
      rats. Nitric oxide (NO) synthase inhibition with L-NNA led to a limited
      contraction in sham rats (8+/-3% of Emax), whereas a significant (P<0.05)
      increase was observed in OVX rats (34+/-12% of Emax). Lastly, vascular
      sensitivity (pD2) to sodium nitroprusside was significantly increased (P<0.05) in
      OVX rats, as compared to sham. 4. Tamoxifen therapy normalized the resting
      tension of isolated cerebral arteries from OVX rats, abrogated phenylephrine
      mediated contraction, and modestly reduced SAP. By contrast, tamoxifen treatment
      of OVX rats did not attenuate L-NNA-mediated contractile response of cerebral
      arteries. 5. These data demonstrate that the cerebral artery isolated from the
      OVX rat was associated with an exaggerated vasoconstrictor response to
      phenylephrine, and altered NO-dependent vascular reactivity. The administration
      of tamoxifen to OVX rats normalized cerebral artery reactivity to phenylephrine.
      These findings provide the impetus to examine the potential therapeutic benefit
      of the partial estrogen receptor agonist tamoxifen to reduce the incidence of
      cerebrovascular stroke in postmenopausal women.

PMID- 14597599
TI  - Alkylglycerol opening of the blood-brain barrier to small and large fluorescence
      markers in normal and C6 glioma-bearing rats and isolated rat brain capillaries.
AB  - 1. The blood-brain barrier (BBB) represents the major impediment to successful
      delivery of therapeutic agents to target tissue within the central nervous
      system. Intracarotid alkylglycerols have been shown to increase the transfer of
      chemotherapeutics across the BBB. 2. We investigated the spatial distribution of
      intracarotid fluorescein sodium and intravenous lissamine-rhodamine B200 (RB 200)
      albumin in the brain of normal and C6 glioma-bearing rats after intracarotid co
      administration of 1-O-pentylglycerol (200 mm). To elucidate the mechanisms
      involved in the alkylglycerol-mediated BBB opening, intraluminal accumulation of
      fluorescein isothiocyanate (FITC)-dextran 40,000 was studied in freshly isolated
      rat brain capillaries using confocal microscopy during incubation with different
      alkylglycerols. Furthermore, 1-O-pentylglycerol-induced increase in delivery of
      methotrexate (MTX) to the brain was evaluated in nude mice. 3. Microscopic
      evaluation showed a marked 1-O-pentylglycerol-induced extravasation of
      fluorescein and RB 200-albumin in the ipsilateral normal brain. In glioma-bearing
      rats, increased tissue fluorescence was found in both tumor tissue and brain
      surrounding tumor. Confocal microscopy revealed a time- and concentration
      dependent accumulation of FITC-dextran 40,000 within the lumina of isolated rat
      brain capillaries during incubation with 1-O-pentylglycerol and 2-O
      hexyldiglycerol, indicating enhanced paracellular transfer via tight junctions.
      Intracarotid co-administration of MTX and 1-O-pentylglycerol (200 mm) in nude
      mice resulted in a significant increase in MTX concentrations in the ipsilateral
      brain as compared to controls without 1-O-pentylglycerol (P<0.005). 4. In
      conclusion, 1-O-pentylglycerol increases delivery of small and large compounds to
      normal brain and brain tumors and this effect is mediated at least in part by
      enhanced permeability of tight junctions.

PMID- 14597598
TI  - Catalase has negligible inhibitory effects on endothelium-dependent relaxations
      in mouse isolated aorta and small mesenteric artery.
AB  - 1. The current study examined the hypothesis that endothelial production of
      hydrogen peroxide (H2O2) mediates relaxations to acetylcholine (ACh) in aorta and
      small mesenteric arteries (SMA) from mice. 2. Relaxations to ACh (0.01-10 microM)
      and H2O2 (0.1-1000 microM) were produced in aorta and SMA isolated from wild-type
      C57BL/6 mice and type II diabetic mice (db/db). In SMA, relaxations to ACh were
      produced in the presence of N omega-nitro-L-arginine methyl ester (100 microM)
      and indomethacin (Indo, 10 microM). 3. 1-H[1,2,4]oxadiazolo[4,3-]quinoxalin-1-one
      (10 microM) significantly reduced ACh-induced relaxations in SMA, abolished
      responses in aorta, but had no effect on relaxations induced by H2O2. Catalase
      (2500 U ml-1) abolished responses to H2O2, but did not alter relaxations to ACh
      in the SMA and only caused a small rightward shift in responses to ACh in the
      aorta. 4. ACh-, but not H2O2-, mediated relaxations were significantly reduced by
      tetraethylammonium (10 mM), the combination of apamin (1 microM) and
      charybdotoxin (100 nM), and 25 mm potassium chloride (KCl). Higher KCl (60 mM)
      abolished relaxations to both ACh and H2O2. Polyethylene glycolated superoxide
      dismutase (100 U ml-1), the catalase inhibitor 3-amino-1,2,4-triazole (3-AT, 50
      mM) and treatment with the copper chelator diethyldithiolcarbamate (3 mM) did not
      affect relaxations to ACh. 5. H2O2-induced relaxations were endothelium
      independent and were not affected by ethylene diamine tetraacetic acid (EDTA
      0.067 mM), 4-aminopyridine (1 mM), ouabain (100 microM) and barium (30 microM), 3
      AT or Indo. 6. Although the data from this study show that H2O2 dilates vessels,
      they do not support the notion that H2O2 mediates endothelium-dependent
      relaxations to ACh in either aorta or SMA from mice.

PMID- 14597600
TI  - IL-13 enhances agonist-evoked calcium signals and contractile responses in airway
      smooth muscle.
AB  - Growing evidence suggests that interleukin (IL)-13, a Th2-type cytokine, plays a
      critical role in the development of bronchial hyper-responsiveness (BHR), an
      essential feature of asthma, although the underlying mechanisms remain unknown.
      In the present study, we investigated whether IL-13 directly affects airway
      smooth muscle (ASM) function. In murine tracheal rings, IL-13 (100 ng ml-1, 24 h)
      significantly increased both the carbachol- and KCl-induced maximal force
      generation without affecting ASM sensitivity. In cultured human ASM cells, IL-13
      (50 ng ml-1, 24 h) also augmented cytosolic calcium levels to bradykinin,
      histamine and carbachol by 60, 35 and 26%, respectively. The present study
      demonstrates that IL-13 may promote BHR by directly modulating ASM contractility,
      an effect that may be due to enhanced G protein-coupled receptor (GPCR)
      associated calcium signaling.

PMID- 14597601
TI  - Verotoxin activates mitogen-activated protein kinase in human peripheral blood
      monocytes: role in apoptosis and proinflammatory cytokine release.
AB  - . In this study, we examined the role of mitogen-activated protein (MAP) kinases
      in the effects of verotoxins (VTs), from Escherichia coli O157:H7, upon both
      apoptosis and the release of tumour necrosis factor alpha (TNF-alpha) and
      granulocyte-macrophage colony-stimulated factor (GM-CSF) from human monocytes. 2.
      Both VT1 and VT2 stimulated a weak, transient increase in c-Jun-N-terminal kinase
      (JNK) activity and a strong activation of both p38 mitogen-activated protein
      kinase (MAP kinase) and extracellular-regulated kinase (ERK) activity in human
      monocytes, which was sustained in the case of p38 MAP kinase. 3. Stimulation of
      human monocytes with VT2 (100 ng ml-1) did not result in an increase in
      apoptosis; however, the toxin stimulated the release of both TNF-alpha and GM
      CSF. 4. Pretreatment of human monocytes with the p38 MAP kinase inhibitor
      SB203580, at concentrations from 100 nM to 10 microM, significantly decreased the
      VT1- and VT2-induced TNF-alpha and GM-CSF release from monocytes. In contrast,
      inhibition of MEK1 with PD98059 only significantly decreased GM-CSF release. 5.
      Pretreatment of monocytes with SP600125 inhibited both GM-CSF and TNF-alpha
      production; however, significant effects upon p38 MAP kinase and ERK activation
      were observed. 6. Taken together, these results suggest a role for p38 MAP kinase
      and ERK in cytokine generation in response to the verotoxins. A role for JNK
      remains undetermined.

PMID- 14597602
TI  - Characterisation of marrubenol, a diterpene extracted from Marrubium vulgare, as
      an L-type calcium channel blocker.
AB  - 1. The objective of the present study was to investigate the mechanism of the
      relaxant activity of marrubenol, a diterpenoid extracted from Marrubium vulgare.
      In rat aorta, marrubenol was a more potent inhibitor of the contraction evoked by
      100 mM KCl (IC50: 11.8+/-0.3 microM, maximum relaxation: 93+/-0.6%) than of the
      contraction evoked by noradrenaline (maximum relaxation: 30+/-1.5%). 2. In fura-2
      loaded aorta, marrubenol simultaneously inhibited the Ca2+ signal and the
      contraction evoked by 100 mM KCl, and decreased the quenching rate of fura-2
      fluorescence by Mn2+. 3. Patch-clamp data obtained in aortic smooth muscle cells
      (A7r5) indicated that marrubenol inhibited Ba2+ inward current in a voltage
      dependent manner (KD: 8+/-2 and 40+/-6 microM at holding potentials of -50 and 
      100 mV, respectively). 4. These results showed that marrubenol inhibits smooth
      muscle contraction by blocking L-type calcium channels.

PMID- 14597603
TI  - Expression and effects of cardiotrophin-1 (CT-1) in human airway smooth muscle
      cells.
AB  - 1. Cellular hypertrophy and/or a reduced rate of apoptosis could increase airway
      smooth muscle mass. As cardiotrophin-1 (CT-1) induces hypertrophy and inhibits
      apoptosis in cardiomyocytes, we tested for the expression and effects of CT-1 in
      human bronchial smooth muscle cells (HBSMC). 2. CT-1 was detected in abundance in
      normal adult human lung and was expressed in both fetal and adult HBSMC. 3.
      Following serum deprivation, CT-1 was released by reintroduction of serum and by
      TGF-beta 2/IL-4 in fetal but not adult cells. TGF-beta 2/IL-4 triggered the
      release of CT-1 in serum-fed adult cells. Hypoxia and strain had no effect on the
      release of CT-1. 4. CT-1 reduced the apoptosis induced both by serum deprivation
      and by Fas antibody/TNF-alpha treatment in adult cells, with greater efficacy
      than other members of the IL-6 superfamily. The MAPK/ERK kinase inhibitor PD98059
      (1-10 microM) reduced the effect of CT-1. Fetal cells were more resistant to
      apoptosis. 5. CT-1 (10 ng ml-1) induced a significant increase in cell size as
      judged by protein/DNA ratios and flow cytometry. No effects on smooth muscle
      alpha-actin or vimentin proteins were noted, although CT-1 qualitatively alters
      the cytostructural distribution of SM22, an actin filament-associated protein,
      and increased SM22 protein abundance. No effect on proliferation or migration was
      evident. 6. These data suggest CT-1 expression primarily in fetal and synthetic
      HBSMC phenotypes. By reducing the rates of apoptosis and inducing hypertrophy, CT
      1 may contribute to increased smooth muscle mass in airway disease.

PMID- 14597604
TI  - Adenosine 3', 5' cyclic monophosphate attenuates the production of fibronectin in
      the glomeruli of anti-glomerular basement membrane antibody-associated nephritic
      rats.
AB  - 1. Excessive production of extracellular matrix is thought to be involved in the
      progression of glomerulonephritis and glomerulosclerosis. In chronic
      glomerulonephritis, fibronectin has been shown to accumulate in the glomeruli,
      accompanied by cell proliferation. 2. Glomerulonephritis was induced in rats by
      the injection of anti-glomerular basement membrane antibody. The rats showed
      proteinuria and histological alterations in the glomeruli. An increase in
      fibronectin levels in the culture medium of isolated nephritic glomeruli was
      confirmed, and was associated with the development of nephritis.
      Immunohistochemical staining demonstrated a marked accumulation of fibronectin in
      the glomeruli of nephritic rats. 3. Attenuated generation of cyclic AMP was also
      observed in the nephritic glomeruli treated with forskolin, prostaglandin E1 or
      adenosine. 4. Forskolin, prostaglandin E2 and 8-bromo-cyclic AMP markedly reduced
      the production of fibronectin by the nephritic glomeruli compared with controls
      in a dose-dependent manner. 8-Bromo-cyclic AMP suppressed the production of
      fibronectin by cultured mesangial cells. 5. These findings suggest that the
      attenuated generation of cyclic AMP in response to ligands is connected to the
      augmented accumulation of fibronectin in nephritic glomeruli, and may facilitate
      the development of methods for treating glomerulonephritis and
      glomerulosclerosis.

PMID- 14597605
TI  - Activation of group III metabotropic glutamate receptors in selected regions of
      the basal ganglia alleviates akinesia in the reserpine-treated rat.
AB  - 1. This study examined whether group III metabotropic glutamate (mGlu) receptor
      agonists injected into the globus pallidus (GP), substantia nigra pars reticulata
      (SNr) or intracerebroventricularly (i.c.v.) could reverse reserpine-induced
      akinesia in the rat. 2. Male Sprague-Dawley rats, cannulated above the GP, SNr or
      third ventricle, were rendered akinetic with reserpine (5 mg kg(-1) s.c.). 18 h
      later, behavioural effects of the group III mGlu receptor agonists L-serine-O
      phosphate (L-SOP) or L-(+)-2-amino-4-phosphonobutyric acid (L-AP4) were examined.
      3. In reserpine-treated rats, unilateral injection of L-SOP (2000 and 2500 nmol
      in 2.5 microl) into the GP produced a significant increase in net contraversive
      rotations compared to vehicle, reaching a maximum of 83+/-21 rotations 120 min(
      1) (n=8). Pretreatment with the group III mGlu receptor antagonist methyl-serine
      O-phosphate (M-SOP; 250 nmol in 2.5 microl) inhibited the response to L-SOP (2000
      nmol) by 77%. Unilateral injection of L-SOP (250-1000 nmol in 2.5 microl) into
      the SNr of reserpine-treated rats produced a dose-dependent increase in net
      contraversive rotations, reaching a maximum of 47+/-6 rotations 30 min(-1) (n=6).
      M-SOP (50 nmol in 2.5 microl) inhibited the response to L-SOP (500 nmol) by 78%.
      4. Following i.c.v. injection, L-SOP (2000-2500 nmol in 2.5 microl) or L-AP4 (0.5
      100 nmol in 2 microl) produced a dose-dependent reversal of akinesia, attaining a
      maximum of 45+/-17 (n=8) and 72+/-3 (n=9) arbitrary locomotor units 30 min(-1),
      respectively. 6. These studies indicate that injection of group III mGlu receptor
      agonists into the GP, SNr or cerebral ventricles reverses reserpine-induced
      akinesia, the mechanism for which remains to be established.

PMID- 14597607
TI  - ADAMTS13 and thrombotic thrombocytopenic purpura-hemolytic uremic syndrome.

PMID- 14597606
TI  - Pharmacological characterisation of a rat model of incisional pain.
AB  - 1. Both clinical and preclinical models of postsurgical pain are being used more
      frequently in the early evaluation of new chemical entities. In order to assess
      the validity and reliability of a rat model of postincisional pain, the effects
      of different classes of clinically effective analgesic drugs were evaluated
      against multiple behavioural end points. 2. Following surgical incision, under
      general anaesthesia, of the plantar surface of the rat hind paw, we determined
      the time course of mechanical hyperalgesia, tactile allodynia and hind limb
      weight bearing using the Randall-Selitto (paw pressure) assay, electronic von
      Frey and dual channel weight averager, respectively. Behavioural evaluations
      began 24 h following surgery, and were continued for 9-14 days. 3. Mechanical
      hyperalgesia, tactile allodynia and a decrease in weight bearing were present on
      the affected limb within 1 day of surgery with maximum sensitivity 1-3 days
      postsurgery. Accordingly, we examined the effect of nonsteroidal antiinflammatory
      drugs (NSAIDs), morphine and gabapentin, on established hyperalgesia and
      allodynia, 1 day following plantar incision.4. In accordance with previous
      reports, both systemic morphine and gabapentin administration reversed mechanical
      hyperalgesia and tactile allodynia in the incised rat hind paw. Both drugs were
      more potent against mechanical hyperalgesia than tactile allodynia. 5. All of the
      NSAIDs tested, including cyclooxygenase 2 selective inhibitors, reversed
      mechanical hyperalgesia and tactile allodynia in the incised rat hind paw. The
      rank order of potency for both hyperalgesia and allodynia was indomethacin >
      celecoxib > etoricoxib > naproxen. 6. We have investigated the potency and
      efficacy of different classes of analgesic drugs in a rat model of postincisional
      pain. The rank order of potency for these drugs reflects their utility in
      treating postoperative pain in the clinic. As these compounds showed reliable
      efficacy across two different behavioural end points, the Randall-Selitto (paw
      pressure) assay and electronic von Frey, these methods may prove useful in the
      study of postsurgical pain and the assessment of novel treatments.

PMID- 14597608
TI  - Central nervous system (CNS) disease in Abelson virus-induced leukemia.

PMID- 14597609
TI  - Mutation analysis of the transcription factor PU.1 in younger adults (16 to 60
      years) with acute myeloid leukemia: a study of the AML Study Group Ulm (AMLSG
      ULM).

PMID- 14597610
TI  - Treating patients of myelodysplastic syndrome with antithymocytic globulin-
      should we be more selective?

PMID- 14597611
TI  - Continuous flow leukapheresis induces expression of stress genes in lymphocytes:
      impact on microarray analyses.

PMID- 14597612
TI  - p42, a novel cyclin-dependent kinase-activating kinase in mammalian cells.
AB  - The cyclin-dependent kinase (CDK)-activating kinase (CAK) phosphorylates a
      conserved threonine residue on CDKs and activates them. Two known classes of CAKs
      are represented by monomeric Cak1p in budding yeast Saccharomyces cerevisiae and
      by heterotrimeric CDK7-cyclin H-Mat1 in human and other metazoa. We report here
      the identification of p42, a novel CAK activity in human cells. p42 has sequence
      homology to both Cak1p and CDK7 groups of CAKs. p42 is essential for the
      phosphorylation of Thr-160 and activation of CDK2. A dominant-negative p42
      mutant, T161A, and posttranscriptional gene silencing of p42 with RNA(i)-impaired
      Thr-160 phosphorylation and activity of CDK2. Purified p42 phosphorylated
      glutathione S-transferase-CDK2 at Thr-160 within the T-loop and activated its
      histone H1 kinase activity. Finally, p42 is indispensable for cell growth. Cells
      lacking p42 were incapable of growing and forming colonies whereas cells with a
      reduced level of p42 grew at significantly slower rates than control cells. Our
      findings suggest that p42 represents a novel CAK activity in mammalian cells.

PMID- 14597613
TI  - Interactions of a family 18 chitinase with the designed inhibitor HM508 and its
      degradation product, chitobiono-delta-lactone.
AB  - We describe enzymological and structural analyses of the interaction between the
      family 18 chitinase ChiB from Serratia marcescens and the designed inhibitor N,N'
      diacetylchitobionoxime-N-phenylcarbamate (HM508). HM508 acts as a competitive
      inhibitor of this enzyme with a K(i) in the 50 microM range. Active site mutants
      of ChiB show K(i) values ranging from 1 to 200 microM, providing insight into
      some of the interactions that determine inhibitor affinity. Interestingly, the
      wild type enzyme slowly degrades HM508, but the inhibitor is essentially stable
      in the presence of the moderately active D142N mutant of ChiB. The crystal
      structure of the D142N-HM508 complex revealed that the two sugar moieties bind to
      the -2 and -1 subsites, whereas the phenyl group interacts with aromatic side
      chains that line the +1 and +2 subsites. Enzymatic degradation of HM508, as well
      as a Trp --> Ala mutation in the +2 subsite of ChiB, led to reduced affinity for
      the inhibitor, showing that interactions between the phenyl group and the enzyme
      contribute to binding. Interestingly, a complex of enzymatically degraded HM508
      with the wild type enzyme showed a chitobiono-delta-lactone bound in the -2 and 
      1 subsites, despite the fact that the equilibrium between the lactone and the
      hydroxy acid forms in solution lies far toward the latter. This shows that the
      active site preferentially binds the (4)E conformation of the -1 sugar, which
      resembles the proposed transition state of the reaction.

PMID- 14597614
TI  - Secretogranin III binds to cholesterol in the secretory granule membrane as an
      adapter for chromogranin A.
AB  - Granin-family proteins, including chromogranin A (CgA) and secretogranin III
      (SgIII), are transported to secretory granules (SGs) in neuroendocrine cells. We
      previously showed that SgIII binds strongly to CgA in an intragranular milieu and
      targets CgA to SGs in pituitary and pancreatic endocrine cells. In this study, we
      demonstrated that with a sucrose density gradient of rat insulinoma-derived INS-1
      cell homogenates, SgIII was localized to the SG fraction and was fractionated to
      the SG membrane (SGM) despite lacking the transmembrane region. With depletion of
      cholesterol from the SGM using methyl-beta-cyclodextrin, SgIII was impaired to
      bind to the SGM. Both SgIII and CgA were solubilized from the SGM by Triton X-100
      in contrast to the Triton X-100 insolubility of carboxypeptidase E. SgIII and
      carboxypeptidase E strongly bound to the SGM-type liposome in intragranular
      conditions, but CgA did not. Instead, CgA bound to the SGM-type liposome only in
      the presence of SgIII. Immunocytochemical and pulse-chase experiments revealed
      that SgIII deleting the N-terminal lipid-binding region missorted to the
      constitutive pathway in mouse corticotroph-derived AtT-20 cells. Thus, we suggest
      that SgIII directly binds to cholesterol components of the SGM and targets CgA to
      SGs in pituitary and pancreatic endocrine cells.

PMID- 14597615
TI  - The yeast mitochondrial proteome, a study of fermentative and respiratory growth.
AB  - Saccharomyces cerevisiae is able to switch from fermentation to respiration
      (diauxic shift) with major changes in metabolic activity. This phenomenon has
      been previously studied on the transcriptional level. Here we present a parallel
      analysis of the yeast mitochondrial proteome and the corresponding
      transcriptional activity in cells grown on glucose (fermentation) and glycerol
      (respiration). A two-dimensional reference gel for this organelle proteome was
      established (available at www.biochem.oulu.fi/proteomics/), which contains about
      800 intense spots. From 459 spots 253 individual proteins were identified, among
      them low abundant and hydrophobic proteins, and 37 proteins previously deemed
      hypothetical, with partially unknown cellular localization. After the diauxic
      shift, mitochondrial levels of only 18 proteins were changed (17 increased, with
      1 decreased), among them proteins involved in the tricarboxylic acid cycle
      (Sdh1p, Sdh2p, and Sdh4p) and the respiratory chain (Cox4p, Cyb2p, and Qcr7p),
      proteins contributing to other respiratory pathways (Ach1p, Adh2p, Ald4p, Cat2p,
      Icl2p, and Pdh1p), and two proteins with unknown function (Om45p and Ybr230p).
      Apart from an overall increase in mitochondrial protein mass, the mitochondrial
      proteome remains remarkably constant, even in a major metabolic adaptation. This
      seemingly disagrees with results of the DNA microarray analyses, where a rather
      heterogenous up- or down-regulation of genes encoding mitochondrial proteins
      implies large changes in the proteome. We propose that the discrepancy between
      proteome and transcriptional regulation, apart from different translation
      efficiency, indicates a changed turnover rate of proteins in different
      physiological conditions.

PMID- 14597616
TI  - Bordetella dermonecrotic toxin undergoes proteolytic processing to be
      translocated from a dynamin-related endosome into the cytoplasm in an
      acidification-independent manner.
AB  - Bordetella pertussis dermonecrotic toxin (DNT), which activates intracellular Rho
      GTPases, is a single chain polypeptide composed of an N-terminal receptor-binding
      domain and a C-terminal enzymatic domain. We found that DNT was cleaved by furin,
      a mammalian endoprotease, on the C-terminal side of Arg(44), which generates an N
      terminal fragment almost corresponding to the receptor-binding domain and a C
      terminal remainder (deltaB) containing the enzymatic domain. These two fragments
      remained associated even after the cleavage and made a nicked form. DNT mutants
      insensitive to furin had no cellular effect, whereas the nicked toxin was much
      more potent than the intact form, indicating that the nicking by furin was a
      prerequisite for action. DeltaB, but not the nicked toxin, associated with
      artificial liposomes and activated Rho in cells resistant to DNT because of a
      lack of surface receptor. These results imply that deltaB, dissociated from the
      binding domain, fully possesses the ability to enter the cytoplasm across the
      lipid bilayer membrane. The translocation ability of deltaB was found to be
      attributable to the N-terminal region encompassing amino acids 45-166, including
      a putative transmembrane domain. Pharmacological analyses with various reagents
      disturbing vesicular trafficking revealed that the translocation requires neither
      the acidification of the endosomes nor retrograde vesicular transport to deeper
      organelles, although DNT appeared to be internalized via a dynamin-dependent
      endocytosis. We conclude that DNT binds to its receptor and is internalized into
      endosomes where the proteolytic processing occurs. DeltaB, liberated from the
      binding domain after the processing, begins to translocate the enzymatic domain
      into the cytoplasm.

PMID- 14597617
TI  - Decreased p21 levels are required for efficient restart of DNA synthesis after S
      phase block.
AB  - The cyclin-dependent kinase inhibitor p21, a major transcriptional target of the
      tumor suppressor p53, plays a critical role in cell cycle arrest in G1 and G2
      after DNA damage. It was previously shown that in some human cell lines when S
      phase is arrested, p53 is transcriptionally impaired such that some p53 targets
      including p21 are only weakly induced. We show here that during S phase arrest
      proteasome-mediated turnover of p21 is significantly increased in a manner that
      is independent of p53. It is well established that p21 can interact both with
      cyclin-dependent kinase complexes and with proliferating cell nuclear antigen
      (PCNA). Interestingly, the scant amount of p21 detected during S phase block
      cannot fully saturate cyclin A-cyclin-dependent kinase 2 complexes and does not
      interact detectably with PCNA. Importantly, DNA elongation assays in isolated
      nuclei show that the C terminus of p21 containing the PCNA-binding domain
      effectively blocks this process. This implies that p21 down-regulation could be
      an essential requirement for efficient restart of DNA synthesis. In line with
      this, only cells expressing low levels of p21 immediately progress through the
      cell cycle upon release from S phase arrest, whereas the remaining few high p21
      producing cells move much more slowly through S. Thus, p21 down-regulation is
      multiply determined and is required for the reversibility of the arrest in S
      phase.

PMID- 14597618
TI  - The insulin-like growth factor 1 receptor induces physiological heart growth via
      the phosphoinositide 3-kinase(p110alpha) pathway.
AB  - Insulin-like growth factor 1 (IGF1) was considered a potential candidate for the
      treatment of heart failure. However, some animal studies and clinical trials have
      questioned whether elevating IGF1 chronically is beneficial. Secondary effects of
      increased serum IGF1 levels on other tissues may explain these unfavorable
      results. The aim of the current study was to examine the role of IGF1 in cardiac
      myocytes in the absence of secondary effects, and to elucidate downstream
      signaling pathways and transcriptional regulatory effects of the IGF1 receptor
      (IGF1R). Transgenic mice overexpressing IGF1R in the heart displayed cardiac
      hypertrophy, which was the result of an increase in myocyte size, and there was
      no evidence of histopathology. IGF1R transgenics also displayed enhanced systolic
      function at 3 months of age, and this was maintained at 12-16 months of age. The
      phosphoinositide 3-kinase (PI3K)-Akt-p70S6K1 pathway was significantly activated
      in hearts from IGF1R transgenics. Cardiac hypertrophy induced by overexpression
      of IGF1R was completely blocked by a dominant negative PI3K(p110alpha) mutant,
      suggesting IGF1R promotes compensated cardiac hypertrophy in a PI3K(p110alpha)
      dependent manner. This study suggests that targeting the cardiac IGF1R
      PI3K(p110alpha) pathway could be a potential therapeutic strategy for the
      treatment of heart failure.

PMID- 14597619
TI  - Promoter binding, initiation, and elongation by bacteriophage T7 RNA polymerase.
      A single-molecule view of the transcription cycle.
AB  - A single-molecule transcription assay has been developed that allows, for the
      first time, the direct observation of promoter binding, initiation, and
      elongation by a single RNA polymerase (RNAP) molecule in real-time. To promote
      DNA binding and transcription initiation, a DNA molecule tethered between two
      optically trapped beads was held near a third immobile surface bead sparsely
      coated with RNAP. By driving the optical trap holding the upstream bead with a
      triangular oscillation while measuring the position of both trapped beads, we
      observed the onset of promoter binding, promoter escape (productive initiation),
      and processive elongation by individual RNAP molecules. After DNA template
      release, transcription re-initiation on the same DNA template is possible; thus,
      multiple enzymatic turnovers by an individual RNAP molecule can be observed.
      Using bacteriophage T7 RNAP, a commonly used RNAP paradigm, we observed the
      association and dissociation (k(off)= 2.9 s(-1)) of T7 RNAP and promoter DNA, the
      transition to the elongation mode (k(for) = 0.36 s(-1)), and the processive
      synthesis (k(pol) = 43 nt s(-1)) and release of a gene-length RNA transcript (
      approximately 1200 nt). The transition from initiation to elongation is much
      longer than the mean lifetime of the binary T7 RNAP-promoter DNA complex (k(off)
      > k(for)), identifying a rate-limiting step between promoter DNA binding and
      promoter escape.

PMID- 14597620
TI  - Hypoxia potentiates nitric oxide-mediated apoptosis in endothelial cells via
      peroxynitrite-induced activation of mitochondria-dependent and -independent
      pathways.
AB  - Nitric oxide (NO*) at low concentrations is cytoprotective for endothelial cells;
      however, elevated concentrations of NO* (> or =1 micromol/liter), as may be
      achieved during inflammatory states, can induce apoptosis and cell death. Hypoxia
      is associated with tissue inflammation and ischemia and, therefore, may modulate
      the effects of NO* on endothelial function. To examine the influence of hypoxia
      on NO*-mediated apoptosis, we exposed bovine aortic endothelial cells (BAEC) to
      (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl) amino]diazen-1-ium-1,2-diolate
      (diethylenetriamine NONOate, DETA-NO) (1 mmol/liter) under normoxic or hypoxic
      conditions (pO2 = 35 mm of Hg) and measured the indices of apoptotic cell death.
      BAEC treated with DETA-NO under normoxic conditions demonstrated increased levels
      of histone-associated DNA fragments, which was confirmed by terminal dUTP nick
      end labeling assay, and hypoxic conditions augmented this response. To determine
      whether mitochondrial dysfunction was one mechanism by which NO* initiated
      apoptosis under hypoxic conditions, we evaluated mitochondrial membrane potential
      in (Psim). Exposure to DETA-NO resulted in a decrease in Psim and concomitant
      release of cytochrome c and caspase-9 activation, which were enhanced by hypoxia.
      By utilizing Rho0 BAEC (Rho0-EC), which lack functional mitochondria, we
      demonstrated that dissipation of Psim was associated with increased reactive
      oxygen species generation and peroxynitrite formation. Moreover, in Rho0-EC we
      identified activation of caspase-8 as part of the mitochondrial-independent
      pathway of apoptosis. To establish that peroxynitrite mediated mitochondrial
      damage and apoptosis, we treated BAEC and Rho0-EC with the peroxynitrite
      scavenger uric acid and found that the indices of apoptosis were decreased
      significantly. These findings confirm that high flux of NO* under hypoxic
      conditions promotes cell death via mitochondrial damage and mitochondrial
      independent mechanisms by peroxynitrite.

PMID- 14597621
TI  - The majority of the Saccharomyces cerevisiae septin complexes do not exchange
      guanine nucleotides.
AB  - We show here that affinity-purified Saccharomyces cerevisiae septin complexes
      contain stoichiometric amounts of guanine nucleotides, specifically GTP and GDP.
      Using a (15)N-dilution assay read-out by liquid chromatography-tandem mass
      spectrometry, we determined that the majority of the bound guanine nucleotides do
      not turn over in vivo during one cell cycle period. In vitro, the isolated S.
      cerevisiae septin complexes have similar GTP binding and hydrolytic properties to
      the Drosophila septin complexes (Field, C. M., al-Awar, O., Rosenblatt, J., Wong,
      M. L., Alberts, B., and Mitchison, T. J. (1996) J. Cell Biol. 133, 605-616). In
      particular, the GTP turnover of septins is very slow when compared with the GTP
      turnover for Ras-like GTPases. We conclude that bound GTP and GDP play a
      structural, rather then regulatory, role for the majority of septins in
      proliferating cells as GTP does for alpha-tubulin.

PMID- 14597622
TI  - Promyelocytic leukemia protein 4 induces apoptosis by inhibition of survivin
      expression.
AB  - The promyelocytic leukemia protein (PML) plays an essential role in multiple
      pathways of apoptosis. Our previous study showed that PML enhances tumor necrosis
      factor-induced apoptosis by inhibiting the NFkappaB survival pathway. To continue
      exploring the mechanism of PML-induced apoptosis, we performed a DNA microarray
      screening of PML target genes using a PML-inducible stable cell line. We found
      that Survivin was one of the downstream target genes of PML. Cotransfection
      experiments demonstrated that PML4 repressed transactivation of the Survivin
      promoter in an isoform-specific manner. Western blot analysis demonstrated that
      induced PML expression down-regulated Survivin. Inversely, PML knockdown by siRNA
      up-regulated Survivin expression. A substantial increase in Survivin expression
      was found in PML-deficient cells. Re-expression of PML in PML-/- mouse embryo
      fibroblasts down-regulated the expression of Survivin. Furthermore, cells
      arrested at the G2/M cell cycle phase expressed a high level of Survivin and a
      significantly lower level of PML. Overexpression of PML in A549 cells reduced
      Survivin expression leading to massive apoptotic cell death associated with
      activation of procaspase 9, caspase 3, and caspase 7. Together, our results
      demonstrate a novel mechanism of PML-induced apoptosis by down-regulation of
      Survivin.

PMID- 14597623
TI  - Transcription factor B contacts promoter DNA near the transcription start site of
      the archaeal transcription initiation complex.
AB  - Transcription initiation in all three domains of life requires the assembly of
      large multiprotein complexes at DNA promoters before RNA polymerase (RNAP)
      catalyzed transcript synthesis. Core RNAP subunits show homology among the three
      domains of life, and recent structural information supports this homology.
      General transcription factors are required for productive transcription
      initiation complex formation. The archaeal general transcription factors TATA
      element-binding protein (TBP), which mediates promoter recognition, and
      transcription factor B (TFB), which mediates recruitment of RNAP, show extensive
      homology to eukaryal TBP and TFIIB. Crystallographic information is becoming
      available for fragments of transcription initiation complexes (e.g. RNAP, TBP-TFB
      DNA, TBP-TFIIB-DNA), but understanding the molecular topography of complete
      initiation complexes still requires biochemical and biophysical characterization
      of protein-protein and protein-DNA interactions. In published work, systematic
      site-specific protein-DNA photocrosslinking has been used to define positions of
      RNAP subunits and general transcription factors in bacterial and eukaryal
      initiation complexes. In this work, we have used systematic site-specific protein
      DNA photocrosslinking to define positions of RNAP subunits and general
      transcription factors in an archaeal initiation complex. Employing a set of 41
      derivatized DNA fragments, each having a phenyl azide photoactivable crosslinking
      agent incorporated at a single, defined site within positions -40 to +1 of the
      gdh promoter of the hyperthermophilic marine archaea, Pyrococcus furiosus (Pf),
      we have determined the locations of PfRNAP subunits PfTBP and PfTFB relative to
      promoter DNA. The resulting topographical information supports the striking
      homology with the eukaryal initiation complex and permits one major new
      conclusion, which is that PfTFB interacts with promoter DNA not only in the TATA
      element region but also in the transcription-bubble region, near the
      transcription start site. Comparison with crystallographic information implicates
      the PfTFB N-terminal domain in the interaction with the transcription-bubble
      region. The results are discussed in relation to the known effects of
      substitutions in the TFB and TFIIB N-terminal domains on transcription initiation
      and transcription start-site selection.

PMID- 14597624
TI  - Gram-positive DsbE proteins function differently from Gram-negative DsbE
      homologs. A structure to function analysis of DsbE from Mycobacterium
      tuberculosis.
AB  - Mycobacterium tuberculosis, a Gram-positive bacterium, encodes a secreted Dsb
      like protein annotated as Mtb DsbE (Rv2878c, also known as MPT53). Because Dsb
      proteins in Escherichia coli and other bacteria seem to catalyze proper folding
      during protein secretion and because folding of secreted proteins is thought to
      be coupled to disulfide oxidoreduction, the function of Mtb DsbE may be to ensure
      that secreted proteins are in their correctly folded states. We have determined
      the crystal structure of Mtb DsbE to 1.1 A resolution, which reveals a
      thioredoxin-like domain with a typical CXXC active site. These cysteines are in
      their reduced state. Biochemical characterization of Mtb DsbE reveals that this
      disulfide oxidoreductase is an oxidant, unlike Gram-negative bacteria DsbE
      proteins, which have been shown to be weak reductants. In addition, the pK(a)
      value of the active site, solvent-exposed cysteine is approximately 2 pH units
      lower than that of Gram-negative DsbE homologs. Finally, the reduced form of Mtb
      DsbE is more stable than the oxidized form, and Mtb DsbE is able to oxidatively
      fold hirudin. Structural and biochemical analysis implies that Mtb DsbE functions
      differently from Gram-negative DsbE homologs, and we discuss its possible
      functional role in the bacterium.

PMID- 14597625
TI  - Chinese hamster ovary K2 cell lipid droplets appear to be metabolic organelles
      involved in membrane traffic.
AB  - The principal lipids in animal cell lipid droplets are cholesterol, cholesterol
      ester, and triglyceride, but the protein composition of this compartment is
      largely unknown. Here we report on the proteomic analysis of lipid droplets.
      Using a combination of mass spectrometry and immunoblotting, we identify nearly
      40 specifically associated proteins in droplets isolated from Chinese hamster
      ovary K2 cells grown in normal medium. The proteins fall in to five groups:
      structural molecules of the droplet-like adipose differentiation-related protein;
      multiple enzymes involved in the synthesis, storage, utilization, and degradation
      of cholesterol esters and triglycerides; multiple, different Rab GTPases known to
      be involved in regulating membrane traffic; signaling molecules such as
      p50RhoGAP; and a group of proteins that do not fit any classification but include
      proteins often found in caveolae/rafts such as caveolin-1 and 2 and flotillin-1.
      The proteome of droplets isolated from cells grown in the presence of oleate is
      largely the same except for an increase in the amount of adipose differentiation
      related protein, caveolin-1, and a protein thought to be involved in phospholipid
      recycling called CGI-58. Based on the protein profile, the lipid droplet appears
      to be a complex, metabolically active organelle that is directly involved in
      membrane traffic and possibly phospholipid recycling. We propose the name
      adiposome for this organelle.

PMID- 14597626
TI  - A WW domain-binding motif within the activation domain of the hematopoietic
      transcription factor NF-E2 is essential for establishment of a tissue-specific
      histone modification pattern.
AB  - Histone H3 methylated at lysine 4 (H3-meK4) co-localizes with hyperacetylated
      histones H3 and H4 in transcriptionally active chromatin, but mechanisms that
      establish H3-meK4 are poorly understood. Previously, we showed that the
      hematopoietic-specific activator NF-E2, which is required for beta-globin
      transcription in erythroleukemia cells, induces histone H3 hyperacetylation and
      H3-meK4 at the adult beta-globin genes (betamajor and betaminor). Chromatin
      immunoprecipitation analysis indicated that NF-E2 occupies hypersensitive site
      two (HS2) of the beta-globin locus control region. The mechanism of NF-E2
      mediated chromatin modification was investigated by complementation analysis in
      NF-E2-null CB3 erythroleukemia cells. The activation domain of the hematopoietic
      specific subunit of NF-E2 (p45/NF-E2) contains two WW domain-binding motifs (PXY
      1 and PXY-2). PXY-1 is required for activation of beta-globin transcription.
      Here, we determined which step in NF-E2-dependent transactivation is PXY-1
      dependent. A p45/NF-E2 mutant lacking 42 amino acids of the activation domain,
      including both PXY motifs, and a mutant lacking only PXY-1 were impaired in
      inducing histone H3 hyperacetylation, H3-meK4, and RNA polymerase II recruitment.
      The PXY motifs were not required for transactivation in the context of a GAL4 DNA
      binding domain fusion to p45/NF-E2 in transient transfection assays. As the PXY-1
      mutant occupied HS2 normally, the chromatin modification defect occurred post-DNA
      binding. PXY-1 was not required for recruitment of the histone acetyltransferases
      cAMP-responsive element-binding protein-binding protein (CBP) and p300 to HS2.
      These results indicate that PXY-1 confers chromatin-specific transcriptional
      activation via interaction with a co-regulator distinct from CBP/p300 or by
      regulating CBP/p300 function.

PMID- 14597627
TI  - Intracellular membrane localization of pseudomonas ExoS and Yersinia YopE in
      mammalian cells.
AB  - ExoS (453 amino acids) is a bi-functional type-III cytotoxin of Pseudomonas
      aeruginosa. Residues 96-233 comprise the Rho GTPase-activating protein (Rho GAP)
      domain, while residues 234-453 comprise the 14-3-3-dependent ADP
      ribosyltransferase domain. Residues 51-72 represent a membrane localization
      domain (MLD), which targets ExoS to perinuclear vesicles within mammalian cells.
      YopE (219 amino acids) is a type-III cytotoxin of Yersinia that is also a Rho
      GAP. Residues 96-219 comprise the YopE Rho GAP domain. While the Rho GAP domains
      of ExoS and YopE share structural homology, unlike ExoS, the intracellular
      localization of YopE within mammalian cells has not been resolved and is the
      subject of this investigation. Deletion mapping showed that the N terminus of
      YopE was required for intracellular membrane localization of YopE in CHO cells. A
      fusion protein containing the N-terminal 84 amino acids of YopE localized to a
      punctate-perinuclear region in mammalian cells and co-localized with a fusion
      protein containing the MLD of ExoS. Residues 54-75 of YopE (termed YopE-MLD) were
      necessary and sufficient for intracellular localization in mammalian cells. The
      YopE-MLD localized ExoS to intracellular membranes and targeted ExoS to ADP
      ribosylate small molecular weight membrane proteins as observed for native type
      III delivered ExoS. These data indicate that the YopE MLD functionally
      complements the ExoS MLD for intracellular targeting in mammalian cells.

PMID- 14597628
TI  - Identification of intracellular residues in the dopamine transporter critical for
      regulation of transporter conformation and cocaine binding.
AB  - Recently we showed evidence that mutation of Tyr-335 to Ala (Y335A) in the human
      dopamine transporter (hDAT) alters the conformational equilibrium of the
      transport cycle. Here, by substituting, one at a time, 16 different bulky or
      charged intracellular residues, we identify three residues, Lys-264, Asp-345, and
      Asp-436, the mutation of which to alanine produces a phenotype similar to that of
      Y335A. Like Y335A, the mutants (K264A, D345A, and D436A) were characterized by
      low uptake capacity that was potentiated by Zn(2+). Moreover, the mutants
      displayed lower affinity for cocaine and other inhibitors, suggesting a role for
      these residues in maintaining the structural integrity of the inhibitor binding
      crevice. The conformational state of K264A, Y335A, and D345A was investigated by
      assessing the accessibility to MTSET ([2-(trimethylammonium)ethyl]
      methanethiosulfonate) of a cysteine engineered into position 159 (I159C) in
      transmembrane segment 3 of the MTSET-insensitive "E2C" background (C90A/C306A).
      Unlike its effect at the corresponding position in the homologous norepinephrine
      transporter (NET I155C), MTSET did not inhibit uptake mediated by E2C I159C.
      Furthermore, no inhibition was observed upon treatment with MTSET in the presence
      of dopamine, cocaine, or Zn(2+). Without Zn(2+), E2C I159C/K264A, E2C
      I159C/Y335A, and E2C I159C/D345A were also not inactivated by MTSET. In the
      presence of Zn(2+) (10 microm), however, MTSET (0.5 mm) caused up to
      approximately 60% inactivation. As in NET I155C, this inactivation was protected
      by dopamine and enhanced by cocaine. These data are consistent with a Zn(2+)
      dependent partial reversal of a constitutively altered conformational equilibrium
      in the mutant transporters. They also suggest that the conformational equilibrium
      produced by the mutations resembles that of the NET more than that of the DAT.
      Moreover, the data provide evidence that the cocaine-bound state of both DAT
      mutants and of the NET is structurally distinct from the cocaine-bound state of
      the DAT.

PMID- 14597629
TI  - Genetic down-regulation of phosphoinositide 3-kinase by bikunin correlates with
      suppression of invasion and metastasis in human ovarian cancer HRA cells.
AB  - Using a cDNA microarray analysis, we previously found that exposure of a highly
      invasive ovarian cancer cell line HRA with bikunin, a Kunitz-type protease
      inhibitor, or bikunin gene overexpression markedly reduced phosphoinositide
      kinase (PI3K) p85 gene expression, demonstrating that PI3K may be a candidate
      bikunin target gene. To clarify how reduced levels of PI3K may confer repressed
      invasiveness, we transfected HRA cells with PI3K p85 antisense
      oligodeoxynucleotide (AS-ODN) and compared the properties of the transfected
      cells with those of parental cells and sense (S)-ODN cells. We have also
      demonstrated previously that transforming growth factor-beta1 (TGF-beta1)
      stimulates urokinase-type plasminogen activator (uPA)-dependent invasion and
      metastasis of HRA cells. Here, we show that 1) TGF-beta1 induced a rapid increase
      of the PI3K activity that was accompanied by increased expression (5-fold) of the
      uPA mRNA; 2) pharmacological inhibition of PI3K or AS-PI3K ODN transfection
      inhibited TGF-beta1-stimulated Akt phosphorylation; 3) both PI3K pharmacological
      inhibitors and forced expression of AS-PI3K ODN reduced TGF-beta1-stimulated uPA
      mRNA and protein expression by approximately 70% compared with controls; 4)
      concentrations of PI3K inhibitors, sufficient to inhibit uPA up-regulation,
      inhibited TGF-beta1-dependent HRA cell invasion; 5) the AS-PI3K ODN cells had a
      decreased ability to invade the extracellular matrix layer as compared with
      controls; and 6) when the AS-PI3K ODN cells were injected intraperitoneally into
      nude mice, the mice developed smaller intraperitoneal tumors and showed longer
      survival. We conclude that PI3K plays an essential role in promoting uPA-mediated
      invasive phenotype in HRA cells. Our data identify a novel role for PI3K as a
      bikunin target gene on uPA up-regulation and invasion.

PMID- 14597630
TI  - Prolonged kappa opioid receptor phosphorylation mediated by G-protein receptor
      kinase underlies sustained analgesic tolerance.
AB  - Kappa opioid receptor (KOR) desensitization was previously shown to follow
      agonist-dependent phosphorylation of serine 369 by G-protein receptor kinase
      (GRK) and beta-arrestin binding in transfected cells. To study the in vivo
      effects induced by phosphorylation of KOR(S369), C57Bl/6 mice were administered
      single or repeated doses of the KOR agonist, U50,488, and isolated brain
      glycoprotein was probed with an antibody, KOR-P, that specifically recognized
      phosphoserine 369 KOR. Western blot analysis using KOR-P antibody showed that
      labeling intensity increased after either single or repeated treatment of mice
      with U50,488 by 59 +/- 22% and 101 +/- 29%, respectively. In contrast, there was
      no change in labeling intensity by nonphosphoselective KOR antibodies following
      acute or chronic in vivo treatment with kappa agonist. Moreover, mice lacking
      GRK3 showed no increase in KOR-P labeling and developed significantly less
      analgesic tolerance following treatment with kappa agonist. The result suggests
      that tolerance to kappa agonists includes phosphorylation of serine 369 within
      KOR by GRK3. Recovery of analgesic potency and reduction of elevated KOR-P
      labeling in wild-type mice both required 2 weeks to return to base line.
      Consistent with these results, in vitro phosphorylation by GRK3 of KOR isolated
      from tolerant mice resulted in 46 +/- 7% less (32)P incorporation than in KOR
      isolated from untreated mice. In addition, in vitro (32)P incorporation returned
      to base line levels only in KOR isolated from tolerant mice allowed to recover
      for 2 weeks. The coincident reversal of analgesic tolerance and slow return to a
      basal phosphorylation state matched the regeneration rate of functional kappa
      receptors following irreversible antagonism and suggested that receptor
      replacement rather than dephosphorylation was required to restore sensitivity.

PMID- 14597632
TI  - Observation of a short, strong hydrogen bond in the active site of hydroxynitrile
      lyase from Hevea brasiliensis explains a large pKa shift of the catalytic base
      induced by the reaction intermediate.
AB  - The hydroxynitrile lyase from Hevea brasiliensis (HbHNL) uses a catalytic triad
      consisting of Ser(80)-His(235)-Asp(207) to enhance the basicity of Ser(80)-O
      gamma for abstracting a proton from the OH group of the substrate cyanohydrin.
      Following the observation of a relatively short distance between a carboxyl
      oxygen of Asp(207) and the N delta(1)(His(235)) in a 1.1 A crystal structure of
      HbHNL, we here show by (1)H and (15)N-NMR spectroscopy that a short, strong
      hydrogen bond (SSHB) is formed between the two residues upon binding of the
      competitive inhibitor thiocyanate to HbHNL: the proton resonance of H-N delta
      1(His(235)) moves from 15.41 ppm in the free enzyme to 19.35 ppm in the complex,
      the largest downfield shift observed so far upon inhibitor binding.
      Simultaneously, the D/H fractionation factor decreases from 0.98 to 0.35. In the
      observable pH range, i.e. between pH 4 and 10, no significant changes in chemical
      shifts (and therefore hydrogen bond strength) were observed for free HbHNL. For
      the complex with thiocyanate, the 19.35 ppm signal returned to 15.41 ppm at
      approximately pH 8, which indicates a pK(a) near this value for the H-N
      epsilon(2)(His(235)). These NMR results were analyzed on the basis of finite
      difference Poisson-Boltzmann calculations, which yielded the relative free
      energies of four protonation states of the His(235)-Asp(207) pair in solution as
      well as in the protein environment with and without bound inhibitor. The
      calculations explain all the NMR features, i.e. they suggest why a short, strong
      hydrogen bond is formed upon inhibitor binding and why this short, strong
      hydrogen bond reverts back to a normal one at approximately pH 8. Importantly,
      the computations also yield a shift of the free energy of the anionic state
      relative to the zwitterionic reference state by about 10.6 kcal/mol, equivalent
      to a shift in the apparent pK(a) of His(235) from 2.5 to 10. This huge inhibitor
      induced increase in basicity is a prerequisite for His(235) to act as general
      base in the HbHNL-catalyzed cyanohydrin reaction.

PMID- 14597633
TI  - Three-dimensional structure of the barley beta-D-glucan glucohydrolase in complex
      with a transition state mimic.
AB  - Glucophenylimidazole (PheGlcIm), a tetrahydroimidazopyridine-type inhibitor and
      4H3 conformer mimic of a glucoside, binds very tightly to a barley beta-d-glucan
      glucohydrolase, with a Ki constant of 2 x 10(-9) m and a DeltaG of 51 kJ mol(-1).
      PheGlcIm binds to the barley beta-d-glucan glucohydrolase approximately 2 x 10(5)
      times tighter than laminarin, which is the best non-synthetic ground-state
      substrate found so far for this enzyme, 10(6) times tighter than 4-nitrophenyl
      beta-d-glucopyranoside, and 2 x 10(7) tighter than glucose. The three-dimensional
      structure of the beta-d-glucan glucohydrolase with bound PheGlcIm indicates that
      the complex resembles a hypothetical transition state during the hydrolytic
      cycle, that the enzyme derives substrate binding energy from the "aglycone"
      portion of the ligand, and that it also reveals an anti-protonation trajectory
      for hydrolysis. Continuous electron densities at the 1.6 sigma level form between
      the three active site residues Asp95, His207, and Asp285, and the C6OH, C7OH,
      C8OH, and C9OH groups of PheGlcIm. These electron densities correspond to the
      most favorable interactions in the three-dimensional structure of the beta-d
      glucan glucohydrolase-PheGlcIm complex and indicate atomic distances equal to or
      less than 2.55 A. The crystallographic data were corroborated with ab initio
      molecular orbital calculations. The data indicate that the 4E conformation of the
      glucose part of PheGlcIm is critical for tight binding and provide the first
      evidence for probable substrate distortion during catalysis by this enzyme.

PMID- 14597631
TI  - The coactivator of transcription CREB-binding protein interacts preferentially
      with the glycosylated form of Stat5.
AB  - The signal transducer and activator of transcription (Stat) gene family comprises
      seven members with similarities in their domain structure and a common mode of
      activation. Members of this gene family mediate interferon induction of gene
      transcription and the response to a large number of growth factors and hormones.
      Extracellular ligand binding to transmembrane receptors causes the intracellular
      activation of associated tyrosine kinases, phosphorylation of Stat molecules,
      dimerization, and translocation to the nucleus. Prolactin-induced phosphorylation
      of Stat5 is a key event in the development and differentiation of mammary
      epithelial cells. In addition to the crucial phosphorylation at tyrosine 694, we
      have identified an O-linked N-acetylglucosamine (O-GlcNAc) as another secondary
      modification essential for the transcriptional induction by Stat5. This
      modification was only found on nuclear Stat5 after cytokine activation. Similar
      observations were made with Stat1, Stat3, and Stat6. Glycosylation of Stat5,
      however, does not seem to be a prerequisite for nuclear translocation. Mass
      spectrometric analysis revealed a glycosylated peptide in the N-terminal region
      of Stat5. Replacement of threonine 92 by an alanine residue (Stat5a-T92A)
      strongly reduced the prolactin induction of Stat5a glycosylation and abolished
      transactivation of a target gene promoter. Only the glycosylated form of Stat5
      was able to bind the coactivator of transcription CBP, an essential interaction
      for Stat5-mediated gene transcription.

PMID- 14597634
TI  - Cytosolic peroxiredoxin attenuates the activation of Jnk and p38 but potentiates
      that of Erk in Hela cells stimulated with tumor necrosis factor-alpha.
AB  - Tumor necrosis factor-alpha (TNF-alpha) induces the activation of all three types
      of mitogen-activated protein kinase (MAPK): c-Jun NH(2)-terminal kinase (JNK),
      p38, and extracellular signal-regulated kinase (ERK). This cytokine also induces
      the production of several types of reactive oxygen species, including H(2)O(2).
      With the use both of HeLa cells expressing wild-type or dominant negative forms
      of the cytosolic peroxidase peroxiredoxin II and of mouse embryonic fibroblasts
      deficient in this protein, we evaluated the roles of H(2)O(2) in the activation
      of MAPKs by TNF-alpha. In vitro kinase assays as well as immunoblot analysis with
      antibodies specific for activated MAPKs indicated that H(2)O(2) produced in
      response to TNF-alpha potentiates the activation of JNK and p38 induced by this
      cytokine but inhibits that of ERK. Our results also suggest that cytosolic
      peroxiredoxins are important regulators of TNF signaling pathways.

PMID- 14597635
TI  - Mechanisms of guanine nucleotide exchange and Rac-mediated signaling revealed by
      a dominant negative trio mutant.
AB  - Rho family GTPases play important roles in a variety of cellular processes,
      including actin cytoskeleton reorganization, transcription activation, and DNA
      synthesis. Dominant negative mutants of Rho GTPases, such as T17NRac1, that block
      the endogenous Rho protein activation by sequestering upstream guanine nucleotide
      exchange factors (GEFs) have been widely used to implicate specific members of
      the Rho family in various signaling pathways. We show here that such an approach
      could produce potentially misleading results since many Rho GEFs can interact
      with multiple Rho proteins promiscuously, and overexpression of one dominant
      negative Rho protein mutant may affect the activity of other members of the Rho
      family. Based on the available structural information, we have identified the
      highly conserved amino acid pairing of Asn(1406)Trio-Asp(65)Rac1 of the GEF-Rho
      GTPase interaction as the critical catalytic machinery required for the Rac1
      GDP/GTP exchange reaction. The N1406A/D1407A mutant of Trio acted dominant
      negatively in vitro by retaining Rac1 binding activity but losing GEF catalytic
      activity and competitively inhibited Rac1 activation by wild type Trio. It
      readily blocked the platelet-derived growth factor (PDGF)-induced lamellipodia
      formation and inhibited the wild type Trio-induced serum response factor
      activation. Moreover the mutant was able to selectively inhibit Dbl-induced Rac1
      activation without affecting RhoA activity in cells. In contrast to the non
      discriminative inhibitory effect displayed by T17NRac1, the Trio mutant was
      ineffective in inhibiting PDGF-stimulated DNA synthesis and Dbl-induced
      transformation, revealing the Rac-independent functions of PDGF and Dbl. These
      studies identify a conserved pair of amino acid residues of the Trio-Rac
      interaction that is likely to be essential to the GEF catalysis of Rho family
      GTPases and demonstrate that a dominant negative mutant derived from a Rho GTPase
      regulator constitutes a new generation of specific inhibitors of Rho GTPase
      signaling pathways.

PMID- 14597636
TI  - Bruton's tyrosine kinase phosphorylates cAMP-responsive element-binding protein
      at serine 133 during neuronal differentiation in immortalized hippocampal
      progenitor cells.
AB  - Bruton's tyrosine kinase (BTK) is a member of the Tec family of kinases, which is
      a subgroup of the nonreceptor cytoplasmic protein tyrosine kinases. BTK has been
      shown to be important in the proliferation, differentiation, and signal
      transduction of B cells. Mutations in BTK result in B cell immune deficiency
      disorders, such as X-linked agammaglobulinemia in humans and X-linked
      immunodeficiency in mice. Although BTK plays multiple roles in the life of a B
      cell, its functional role in neuronal cells has not been elucidated. In the
      present study, we demonstrate that BTK activates transcription factor, cAMP
      response element (CRE)-binding protein (CREB), and subsequent CRE-mediated gene
      transcription during basic fibroblast growth factor (bFGF)-induced neuronal
      differentiation in immortalized hippocampal progenitor cells (H19-7). The kinase
      activity of BTK is also induced by bFGF, and BTK directly phosphorylates CREB at
      Ser-133 residue, indicating that BTK has a dual protein kinase activity. In
      addition, blockading BTK activation significantly inhibits CREB phosphorylation
      as well as the neurite outgrowth induced by bFGF in H19-7 cells. These results
      suggest that the activation of BTK and the subsequent phosphorylation of CREB at
      Ser-133 are important in the neuronal differentiation of hippocampal progenitor
      cells.

PMID- 14597637
TI  - The AzgA purine transporter of Aspergillus nidulans. Characterization of a
      protein belonging to a new phylogenetic cluster.
AB  - The azgA gene of Aspergillus nidulans encodes a hypoxanthine-adenine-guanine
      transporter. It has been cloned by a novel transposon methodology. The null
      phenotype of azgA was defined by a number of mutations, including a large
      deletion. In mycelia, the azgA gene is, like other genes of purine catabolism,
      induced by uric acid and repressed by ammonium. Its transcription depends on the
      pathway-specific UaY zinc binuclear cluster protein and the broad domain AreA
      GATA factor. AzgA is not closely related to any other characterized membrane
      protein, but many close homologues of unknown function are present in fungi,
      plants, and prokaryotes but not metazoa. Two of three data bases and the
      phylogeny presented in this article places proteins of this family in a cluster
      clearly separated (but perhaps phylogenetically related) from the NAT family that
      includes other eukaryotic and prokaryotic nucleobase transporters. Thus AzgA is
      the first characterized member of this family or subfamily of membrane proteins.

PMID- 14597638
TI  - Nuclear role of I kappa B Kinase-gamma/NF-kappa B essential modulator (IKK
      gamma/NEMO) in NF-kappa B-dependent gene expression.
AB  - The I kappa B kinase (IKK) complex, which is composed of the two kinases IKK
      alpha and IKK beta and the regulatory subunit IKK gamma/nuclear factor-kappa B
      (NF-kappa B) essential modulator (NEMO), is important in the cytokine-induced
      activation of the NF-kappa B pathway. In addition to modulation of IKK activity,
      the NF-kappa B pathway is also regulated by other processes, including the
      nucleocytoplasmic shuttling of various components of this pathway and the post
      translational modification of factors bound to NF-kappa B-dependent promoters. In
      this study, we explored the role of the nucleocytoplasmic shuttling of components
      of the IKK complex in the regulation of the NF-kappa B pathway. IKK gamma/NEMO
      was demonstrated to shuttle between the cytoplasm and the nucleus and to interact
      with the nuclear coactivator cAMP-responsive element-binding protein-binding
      protein (CBP). Using both in vitro and in vivo analysis, we demonstrated that IKK
      gamma/NEMO competed with p65 and IKK alpha for binding to the N terminus of CBP,
      inhibiting CBP-dependent transcriptional activation. These results indicate that,
      in addition to the key role of IKK gamma/NEMO in regulating cytokine-induced IKK
      activity, its ability to shuttle between the cytoplasm and the nucleus and to
      bind to CBP can lead to transcriptional repression of the NF-kappa B pathway.

PMID- 14597639
TI  - The soluble sema domain of the RON receptor inhibits macrophage-stimulating
      protein-induced receptor activation.
AB  - RON is a receptor tyrosine kinase of the MET family that is involved in cell
      proliferation, cell survival, and cell motility in both normal and disease
      states. Macrophage-stimulating protein (MSP) is the RON ligand whose binding to
      RON causes receptor activation. RON is a trans-membrane heterodimer comprised of
      one alpha- and one beta-chain originating from a single-chain precursor and held
      together by several disulfide bonds. The intracellular part of RON contains the
      kinase domain and regulatory elements. The extracellular region is characterized
      by the presence of a sema domain (a stretch of approximately 500 amino acids with
      several highly conserved cysteine residues), a PSI (plexin, semaphorins,
      integrins) domain, and four immunoglobulin-like folds. Here we show that a
      soluble, secreted molecule representing the sema domain of RON (referred to as
      ron-sema) has a dominant negative effect on the ligand-induced receptor
      activation and is capable of inhibiting RON-dependent signaling pathways and
      cellular responses. Results suggest that the sema domain of RON participates in
      ligand binding by the full-length receptor. The ability of ron-sema to suppress
      growth of MSP-responsive cells in culture, including cancer cells, points to a
      potential therapeutic use of this molecule, and forced expression of it could
      potentially be used as a gene therapy tool for treating MSP-dependent types of
      cancer.

PMID- 14597640
TI  - Association between blood pressure and C-reactive protein levels in acute
      ischemic stroke.
AB  - Among patients with acute stroke, high blood pressure (BP) and higher levels of
      circulating C-reactive protein (CRP) at the entry are often associated with poor
      outcome, although the reason is unclear. If the link between BP and stroke
      outcome is indeed mediated by inflammatory response, one would expect to see
      positive associations between BP and CRP. In a prospective observational stroke
      data bank involving 535 first-ever ischemic stroke patients, we studied the
      association between BP and baseline concentrations of CRP within 24 hours after
      stroke onset. The association between BP components and the odds of having an
      elevated CRP level (> or =1.5 mg/dL) was assessed by logistic regression
      analysis. An increase in systolic BP (SBP), diastolic BP (DBP), mean arterial
      pressure (MAP), or pulse pressure (PP) was significantly associated with an
      increase in the odds of having an elevated CRP level, independent of other
      associated study factors. For each 10 mm Hg increase in SBP, DBP, MAP, or PP, the
      odds of having a high CRP level increased by 72% (P<0.0001), 10% (P<0.0001), 21%
      (P<0.0001), and 10% (P<0.0001), respectively. When the same model was rerun,
      adjusting for all considered BP components, only SBP significantly increased the
      odds of an elevated CRP level by 77% (P<0.0001). Increased SBP was significantly
      associated with elevated levels of circulating CRP in ischemic stroke patients.
      These findings support a possible role of acute hypertension after stroke as an
      inflammatory stimulus contributing to ischemic brain inflammation.

PMID- 14597641
TI  - Blood pressure lowering in essential hypertension with an oral renin inhibitor,
      aliskiren.
AB  - Inhibition of the first and rate-limiting step of the renin-angiotensin system
      has long been an elusive therapeutic goal. Aliskiren, the first known
      representative of a new class of completely nonpeptide, orally active, renin
      inhibitors, has been shown to inhibit the production of angiotensin I and II in
      healthy volunteers and to reduce blood pressure (BP) in sodium-depleted
      marmosets. The aim of this randomized, double-blind, active comparator trial
      study was to assess the BP-lowering efficacy and safety of aliskiren. Two hundred
      twenty-six patients, 21 to 70 years of age, with mild to moderate hypertension,
      were randomly assigned to receive 37.5 mg, 75 mg, 150 mg, or 300 mg aliskiren or
      100 mg losartan daily for 4 weeks. Dose-dependent reductions in daytime
      ambulatory systolic pressure (mean change, mm Hg [SD of change]; -0.4 [11.7], 
      5.3 [11.3], -8.0 [11.0], and -11.0 [11.0], P=0.0002) and in plasma renin activity
      (median change % [interquartile range]; -55 [-64, -11], -60 [-82, -46], -77 [-86,
      -72], and -83 [-92, -71], P=0.0008) were observed with 37.5, 75, 150, and 300 mg
      aliskiren. The change in daytime systolic pressure with 100 mg losartan (-10.9
      [13.8]) was not significantly different from the changes seen with 75, 150, and
      300 mg aliskiren. Aliskiren was well tolerated at all doses studied. This study
      demonstrates that aliskiren, through inhibition of renin, is an effective and
      safe orally active BP-lowering agent. Whether renin inhibition results in
      protection from heart attack, stroke, and nephropathy, similar to angiotensin
      converting enzyme inhibition and angiotensin receptor blockade, needs to be
      researched.

PMID- 14597642
TI  - Plasma homocysteine, hypertension incidence, and blood pressure tracking: the
      Framingham Heart Study.
AB  - Plasma homocysteine is cross-sectionally associated with blood pressure in large,
      community-based studies. It is unknown whether elevated plasma homocysteine
      predicts hypertension incidence. We investigated the relations of baseline plasma
      total homocysteine levels to hypertension incidence and blood pressure tracking
      in 2104 Framingham Heart Study participants (mean age, 57 years; 58% women), who
      were free of hypertension, myocardial infarction, heart failure, atrial
      fibrillation, or renal failure at baseline. Baseline mean+/-SD plasma
      homocysteine was 10.1+/-3.7 micromol/L. On follow-up 4 years from baseline, 360
      persons (17.1%) had developed hypertension, and 878 persons (41.7%) had
      progressed to a higher blood pressure stage. In unadjusted analyses, a 1-SD
      higher log homocysteine value was associated with increased odds of developing
      hypertension (odds ratio [OR], 1.18; 95% confidence interval [CI], 1.05 to 1.32)
      and increased odds of blood pressure progression (OR, 1.17; 95% CI, 1.07 to
      1.27). The relations of plasma homocysteine to the incidence of hypertension or
      blood pressure progression were statistically nonsignificant in age- and sex
      adjusted logistic regression models (OR, 0.98; 95% CI, 0.87 to 1.11 and OR, 1.05;
      95% CI, 0.96 to 1.16, respectively) and in multivariable models adjusted for age,
      sex, body mass index, diabetes, interim weight change, smoking, serum creatinine,
      baseline blood pressure, and blood pressure category (OR, 0.92; 95% CI, 0.81 to
      1.06 and OR, 1.07; 95% CI, 0.97 to 1.18, respectively). In conclusion, we found
      no major relation of baseline plasma homocysteine levels to hypertension
      incidence or longitudinal blood pressure progression in a large, community-based
      cohort of nonhypertensive individuals after adjustment for age, sex, and other
      important covariates.

PMID- 14597643
TI  - Regulation of catecholamines by sustained and intermittent hypoxia in
      neuroendocrine cells and sympathetic neurons.
AB  - Chronic intermittent hypoxia, a characteristic feature of sleep-disordered
      breathing, induces hypertension through augmented sympathetic nerve activity and
      requires the presence of functional carotid body arterial chemoreceptors. In
      contrast, chronic sustained hypoxia does not alter blood pressure. We therefore
      analyzed the biosynthetic pathways of catecholamines in peripheral nervous system
      structures involved in the pathogenesis of intermittent hypoxia-induced
      hypertension, namely, carotid bodies, superior cervical ganglia, and adrenal
      glands. Rats were exposed to either intermittent hypoxia (90 seconds of room air
      alternating with 90 seconds of 10% O2) or to sustained hypoxia (10% O2) for 1 to
      30 days. Dopamine, norepinephrine, epinephrine, dihydroxyphenylacetic acid, and 5
      hydroxytyptamine contents were measured by high-performance liquid
      chromatography. Expression of tyrosine hydroxylase and its phosphorylated forms,
      dopamine beta-hydroxylase, phenylethanolamine N-methyltransferase, and GTP
      cyclohydrolase-1 were determined by Western blot analyses. Both sustained and
      intermittent hypoxia significantly increased dopamine and norepinephrine content
      in carotid bodies but not in sympathetic ganglia or adrenal glands. In carotid
      bodies, both types of hypoxia augmented total levels of tyrosine hydroxylase
      protein and its phosphorylation on serines 19, 31, 40, as well as levels of GTP
      cyclohydrolase-1. However, the effects of intermittent hypoxia on
      catecholaminergic pathways were significantly smaller and delayed than those
      induced by sustained hypoxia. Thus, attenuated induction of catecholaminergic
      phenotype by intermittent hypoxia in carotid body may play a role in development
      of hypertension associated with sleep-disordered breathing. The effects of both
      types of hypoxia on expression of catecholaminergic enzymes in superior cervical
      neurons and adrenal glands were transient and small.

PMID- 14597644
TI  - Effect of blood pressure on early decline in kidney function among hypertensive
      men.
AB  - Few cohort studies have examined the longitudinal association between change in
      blood pressure and decline in kidney function among treated hypertensive patients
      without chronic kidney disease. We conducted a nonconcurrent cohort study to
      examine the effects of blood pressure on estimated glomerular filtration rate and
      early kidney function decline (rise in serum creatinine > or =0.6 mg/dL during
      follow-up) among 504 African-American and 218 white hypertensive patients. Our
      results showed that each standard deviation higher treated systolic (18 mm Hg)
      and diastolic (10 mm Hg) blood pressure was associated with an average annual
      decline (95% confidence interval [CI]) in estimated glomerular filtration rate of
      -0.92 ([-1.49 to -0.36] P=0.001) and -0.83 ([-1.38 to -0.28] P=0.003) mL x min(
      1) x 1.73 m(-2), respectively, after adjustment for race, age, education, income,
      use of antihypertensive drugs, body mass index, and history of diabetes and
      dyslipidemia. Likewise, each standard deviation higher systolic and diastolic
      blood pressure was associated with relative risks (95% CIs) of 1.81 ([1.29 to
      2.55] P<0.001) and 1.55 ([1.08 to 2.22] P=0.046), respectively, for early kidney
      function decline. Compared with patients with a blood pressure level <140/90 mm
      Hg, those with a blood pressure level > or =160/95 mm Hg had a -2.67 ([-4.01 to 
      1.32] P<0.001) mL x min(-1) x 1.73 m(-2) greater annual decline in estimated
      glomerular filtration rate and a 5.21-fold ([2.06 to 13.21] P<0.001) greater risk
      of early kidney function decline. Our study found that higher levels of treated
      blood pressure were positively and significantly related to early decline in
      kidney function among hypertensive men. These results indicate that better blood
      pressure control might prevent the onset of chronic kidney disease among
      hypertensives.

PMID- 14597645
TI  - Role of superoxide in modulating the renal effects of angiotensin II.
AB  - Angiotensin II is known to stimulate NADPH oxidase-dependent superoxide (O2-)
      generation, which may contribute to the acute renal vasoconstrictor and
      antinatriuretic actions of this peptide. To evaluate this hypothesis, the effects
      of a superoxide dismutase mimetic (tempol) or a NADPH inhibitor (apocynin) on the
      angiotensin renal actions were studied. Renal cortical nitric oxide (NO) was
      measured electrochemically in vivo. Tempol increased sodium excretion and NO
      levels. Apocynin raised renal blood flow, glomerular filtration rate, sodium
      excretion, and NO levels. These results indicate the presence of an endogenous
      NADPH oxidase-dependent O2- generation that may modulate renal function by
      scavenging NO. Angiotensin II infusion reduced renal blood flow, glomerular
      filtration, sodium excretion, and NO levels in a dose-dependent manner. The
      angiotensin receptor antagonist valsartan, tempol, or apocynin blunted the
      angiotensin effects on renal excretion and NO, suggesting that angiotensin
      receptors stimulation induces the NADPH oxidase-dependent O2- generation that
      might reduce NO bioavailability. This idea is supported by the finding that
      angiotensin increased O2- generation in renal homogenates, and this effect was
      prevented by valsartan, apocynin, or tempol. These results indicate that some of
      the acute renal effects of angiotensin II may be enhanced by an increased NADPH
      oxidase-derived O2- production that reduces renal NO bioavailability.

PMID- 14597647
TI  - Neither perceived job stress nor individual cardiovascular reactivity predict
      high blood pressure.
AB  - We have reported that high job strain was associated with a significantly higher
      diastolic blood pressure (DBP) of 4.5 mm Hg during the working hours,
      irrespective of BP reactivity to a stress test. We report the final results of
      the first 5-year follow-up study, which aimed to assess the respective influences
      of perception of professional strain and cardiovascular reactivity to a mental
      stress test on BP. A cohort of 292 healthy subjects (mean+/-SEM age, 38+/-1
      years) was followed up for progression to hypertension outcome, which was defined
      as an increase in systolic blood pressure (SBP) or DBP >7 mm Hg or a DBP >95 mm
      Hg during follow-up. None of the subjects was lost to follow-up, and 209 subjects
      completed the study. The high-strain (HS) group, representing 20.9% of the
      subjects, was compared with the remaining subjects (non-high-strain [NHS]).
      Similarly, the subjects with the highest BP stress reactivity (HR; 20.9% of
      subjects) were compared with the remaining subjects (NHR). Progression to
      hypertension was reached by 93 subjects (31.8%). Kaplan-Meier survival estimates
      revealed that neither HS nor HR increased the incidence of progression to
      hypertension. End-of-follow-up 24-hour ambulatory BPs that were similar in HS and
      NHS (120+/-2 vs 120+/-1 mm Hg, respectively) and in HR and NHR (122+/-2 vs 120+/
      1 mm Hg, respectively) confirmed our findings. Age, alcohol, salt diet, body mass
      index, and occupation did not interfere with our results. In conclusion,
      cardiovascular HR and HS do not appear to be major risk markers for future high
      BP in healthy, young adults.

PMID- 14597646
TI  - Effect of intravenous angiotensin II infusion on responses to hypothalamic PVN
      injection of bicuculline.
AB  - The hypothalamic paraventricular nucleus (PVN) plays an important role in the
      sympathoexcitatory response to elevated plasma angiotensin II (Ang II). However,
      the mechanism by which Ang II influences sympathetic activity is not fully
      understood. In this study, we tested the hypothesis that GABA(gamma-aminobutyric
      acid)-ergic function in the PVN is reduced by peripheral infusion of Ang II. To
      accomplish this, rats received either intravenous Ang II (12 ng/kg per minute) or
      vehicle (D5W) for 7 days, and renal sympathetic nerve activity (SNA), mean
      arterial pressure (MAP), and heart rate (HR) responses were recorded after
      unilateral PVN microinjection of the GABA-A receptor antagonist bicuculline
      methiodide (BMI, 0.1 nmol). Results indicate that in contrast to a significant
      increase in renal SNA, MAP, and HR observed in vehicle-infused rats (P<0.05), BMI
      injection into the PVN of Ang II-infused animals was without effect on all
      recorded variables. In a separate groups of animals, ganglionic blockade produced
      a significantly greater fall in MAP (P<0.01) in Ang II-infused rats than in
      vehicle-infused control rats, indicating that the contribution of SNA to the
      maintenance of blood pressure was elevated in the Ang II-infused group. Overall,
      these data indicate that cardiovascular and sympathoexcitatory responses to acute
      GABA-A receptor antagonism in the PVN are significantly blunted in rats after 7
      days of intravenous infusion of Ang II. We conclude that an Ang II-induced
      reduction in GABAergic inhibition within the PVN may contribute to elevated SNA
      observed in this study.

PMID- 14597651
TI  - Systems biology is taking off.

PMID- 14597652
TI  - A biophysical approach to transcription factor binding site discovery.
AB  - Identification of transcription factor binding sites within regulatory segments
      of genomic DNA is an important step toward understanding of the regulatory
      circuits that control expression of genes. Here, we describe a novel
      bioinformatics method that bases classification of potential binding sites
      explicitly on the estimate of sequence-specific binding energy of a given
      transcription factor. The method also estimates the chemical potential of the
      factor that defines the threshold of binding. In contrast with the widely used
      information-theoretic weight matrix method, the new approach correctly describes
      saturation in the transcription factor/DNA binding probability. This results in a
      significant improvement in the number of expected false positives, particularly
      in the ubiquitous case of low-specificity factors. In the strong binding limit,
      the algorithm is related to the "support vector machine" approach to pattern
      recognition. The new method is used to identify likely genomic binding sites for
      the E. coli transcription factors collected in the DPInteract database. In
      addition, for CRP (a global regulatory factor), the likely regulatory modality
      (i.e., repressor or activator) of predicted binding sites is determined.

PMID- 14597653
TI  - Limitations of quantitative gene regulation models: a case study.
AB  - Understanding the relationship between network structure and behavior is
      fundamental to the field of computational and systems biology. A particularly
      important distinction is the extent to which qualitative aspects of network
      performance are encoded in network topology as opposed to being determined
      through quantitative details, such as those of kinetics. Here, we develop a
      general and rigorous mathematical framework for the analysis of genetic networks
      and apply it to a family of synthetic gene networks. A key feature of our
      methodology involves determining network behavior that is insensitive to kinetic
      parameters such as rate constants and nonlinear functional dependencies of rates
      on molecular concentrations. Results indicate that behavior observed in some
      networks cannot be reconciled with standard gene expression and regulation
      models. We explore relaxing model assumptions to explain the observed behavior,
      allowing for both dynamic and stochastic phenomena, and propose an alternative
      model. Our alternative model includes the suggestion of a new mechanism by which
      the counterintuitive behavior could be achieved; central to the model is the
      assumption that the Clp protein degradation system, which is responsible for the
      regulatory proteins used in this study, becomes saturated.

PMID- 14597654
TI  - Importance of input perturbations and stochastic gene expression in the reverse
      engineering of genetic regulatory networks: insights from an identifiability
      analysis of an in silico network.
AB  - Gene expression profiles are an increasingly common data source that can yield
      insights into the functions of cells at a system-wide level. The present work
      considers the limitations in information content of gene expression data for
      reverse engineering regulatory networks. An in silico genetic regulatory network
      was constructed for this purpose. Using the in silico network, a formal
      identifiability analysis was performed that considered the accuracy with which
      the parameters in the network could be estimated using gene expression data and
      prior structural knowledge (which transcription factors regulate which genes) as
      a function of the input perturbation and stochastic gene expression. The analysis
      yielded experimentally relevant results. It was observed that, in addition to
      prior structural knowledge, prior knowledge of kinetic parameters, particularly
      mRNA degradation rate constants, was necessary for the network to be
      identifiable. Also, with the exception of cases where the noise due to stochastic
      gene expression was high, complex perturbations were more favorable for
      identifying the network than simple ones. Although the results may be specific to
      the network considered, the present study provides a framework for posing similar
      questions in other systems.

PMID- 14597655
TI  - Regulatory network of Escherichia coli: consistency between literature knowledge
      and microarray profiles.
AB  - The transcriptional network of Escherichia coli may well be the most complete
      experimentally characterized network of a single cell. A rule-based approach was
      built to assess the degree of consistency between whole-genome microarray
      experiments in different experimental conditions and the accumulated knowledge in
      the literature compiled in RegulonDB, a data base of transcriptional regulation
      and operon organization in E. coli. We observed a high and statistical
      significant level of consistency, ranging from 70%-87%. When effector metabolites
      of regulatory proteins are not considered in the prediction of the active or
      inactive state of the regulators, consistency falls by up to 40%. Similarly,
      consistency decreases when rules for multiple regulatory interactions are altered
      or when "on" and "off" entries were assigned randomly. We modified the initial
      state of regulators and evaluated the propagation of errors in the network that
      do not correlate linearly with the connectivity of regulators. We interpret this
      deviation mainly as a result of the existence of redundant regulatory
      interactions. Consistency evaluation opens a new space of dialogue between theory
      and experiment, as the consequences of different assumptions can be evaluated and
      compared.

PMID- 14597656
TI  - Fast evaluation of fluctuations in biochemical networks with the linear noise
      approximation.
AB  - Biochemical networks in single cells can display large fluctuations in molecule
      numbers, making mesoscopic approaches necessary for correct system descriptions.
      We present a general method that allows rapid characterization of the stochastic
      properties of intracellular networks. The starting point is a macroscopic
      description that identifies the system's elementary reactions in terms of rate
      laws and stoichiometries. From this formulation follows directly the stationary
      solution of the linear noise approximation (LNA) of the Master equation for all
      the components in the network. The method complements bifurcation studies of the
      system's parameter dependence by providing estimates of sizes, correlations, and
      time scales of stochastic fluctuations. We describe how the LNA can give precise
      system descriptions also near macroscopic instabilities by suitable variable
      changes and elimination of fast variables.

PMID- 14597657
TI  - Toward rigorous comprehension of biological complexity: modeling, execution, and
      visualization of thymic T-cell maturation.
AB  - One of the problems biologists face is a data set too large to comprehend in
      full. Experimenters generate data at an ever-growing pace, each from their own
      niche of interest. Current theories are each able, at best, to capture and model
      only a small part of the data. We aim to develop a general approach to modeling
      that will help broaden biological understanding. T-cell maturation in the thymus
      is a telling example of the accumulation of experimental data into a large
      disconnected data set. The thymus is responsible for the maturation of stem cells
      into mature T cells, and its complexity divides research into different fields,
      for example, cell migration, cell differentiation, histology, electron
      microscopy, biochemistry, molecular biology, and more. Each field forms its own
      viewpoint and its own set of data. In this study we present the results of a
      comprehensive integration of large parts of this data set. The integration is
      performed in a two-tiered visual manner. First, we use the visual language of
      Statecharts, which makes specification precise, legible, and executable on
      computers. We then set up a moving graphical interface that dynamically animates
      the cells, their receptors, the different gradients, and the interactions that
      constitute thymic maturation. This interface also provides a means for
      interacting with the simulation.

PMID- 14597658
TI  - Cytoscape: a software environment for integrated models of biomolecular
      interaction networks.
AB  - Cytoscape is an open source software project for integrating biomolecular
      interaction networks with high-throughput expression data and other molecular
      states into a unified conceptual framework. Although applicable to any system of
      molecular components and interactions, Cytoscape is most powerful when used in
      conjunction with large databases of protein-protein, protein-DNA, and genetic
      interactions that are increasingly available for humans and model organisms.
      Cytoscape's software Core provides basic functionality to layout and query the
      network; to visually integrate the network with expression profiles, phenotypes,
      and other molecular states; and to link the network to databases of functional
      annotations. The Core is extensible through a straightforward plug-in
      architecture, allowing rapid development of additional computational analyses and
      features. Several case studies of Cytoscape plug-ins are surveyed, including a
      search for interaction pathways correlating with changes in gene expression, a
      study of protein complexes involved in cellular recovery to DNA damage, inference
      of a combined physical/functional interaction network for Halobacterium, and an
      interface to detailed stochastic/kinetic gene regulatory models.

PMID- 14597659
TI  - Sexual dimorphism of hepatic gene expression: novel biological role of KRAB zinc
      finger repressors revealed.

PMID- 14597660
TI  - Oxygen sensing in the hypoxic response pathway: regulation of the hypoxia
      inducible transcription factor.

PMID- 14597661
TI  - mBtd is required to maintain signaling during murine limb development.
AB  - buttonhead (btd) encodes an SP1-like transcription factor required for the
      generation and specification of Drosophila head segments. We identified a murine
      btd homolog, termed mouse Btd (mBtd), which can support btd-dependent head
      development in transgenic fly embryos. Functional studies show that mBtd
      deficient mice develop to term and die at birth. They exhibit brain
      malformations, posterior axial skeleton truncations, and shortened limbs. We
      present evidence that mBtd is required during early limb development to maintain,
      but not to initiate Wnt/beta-catenin-dependent FGF, Shh, and BMP-mediated
      signaling. The data indicate that mBtd represents a novel key player mediating
      proximodistal outgrowth of the limb.

PMID- 14597662
TI  - The COP1-SPA1 interaction defines a critical step in phytochrome A-mediated
      regulation of HY5 activity.
AB  - Arabidopsis COP1 is a constitutive repressor of photomorphogenesis that interacts
      with photomorphogenesis-promoting factors such as HY5 to promote their proteasome
      mediated degradation. SPA1 is a repressor of phytochrome A-mediated responses to
      far-red light. Here we report that COP1 acts as part of a large protein complex
      and interacts with SPA1 in a light-dependent manner. We further demonstrate the
      E3 ubiquitin ligase activity of COP1 on HY5 in vitro and the alteration of that
      activity by SPA1. Thus, the COP1-SPA1 interaction defines a critical step in
      coordinating COP1-mediated ubiquitination and subsequent degradation of HY5 with
      PHYA signaling.

PMID- 14597663
TI  - An mRNA structure in bacteria that controls gene expression by binding lysine.
AB  - Riboswitches are metabolite-responsive genetic control elements that reside in
      the untranslated regions (UTRs) of certain messenger RNAs. Herein, we report that
      the 5'-UTR of the lysC gene of Bacillus subtilis carries a conserved RNA element
      that serves as a lysine-responsive riboswitch. The ligand-binding domain of the
      riboswitch binds to L-lysine with an apparent dissociation constant (KD) of
      approximately 1 micro M, and exhibits a high level of molecular discrimination
      against closely related analogs, including D-lysine and ornithine. Furthermore,
      we provide evidence that this widespread class of riboswitches serves as a target
      for the antimetabolite S-(2-aminoethyl)-L-cysteine (AEC). These findings add
      support to the hypotheses that direct sensing of metabolites by messenger RNAs is
      a fundamental form of genetic control and that riboswitches represent a new class
      of antimicrobial drug targets.

PMID- 14597664
TI  - Negative regulation of calcineurin signaling by Hrr25p, a yeast homolog of casein
      kinase I.
AB  - Calcineurin is a Ca2+/calmodulin-regulated protein phosphatase required for
      Saccharomyces cerevisiae to respond to a variety of environmental stresses.
      Calcineurin promotes cell survival during stress by dephosphorylating and
      activating the Zn-finger transcription factor Crz1p/Tcn1p. Using a high
      throughput assay, we screened 119 yeast kinases for their ability to
      phosphorylate Crz1p in vitro and identified the casein kinase I homolog Hrr25p.
      Here we show that Hrr25p negatively regulates Crz1p activity and nuclear
      localization in vivo. Hrr25p binds to and phosphorylates Crz1p in vitro and in
      vivo. Overexpression of Hrr25p decreases Crz1p-dependent transcription and
      antagonizes its Ca2+-induced nuclear accumulation. In the absence of Hrr25p,
      activation of Crz1p by Ca2+/calcineurin is potentiated. These findings represent
      the first identification of a negative regulator for Crz1p, and establish a novel
      physiological role for Hrr25p in antagonizing calcineurin signaling.

PMID- 14597665
TI  - Smoothened transduces Hedgehog signal by physically interacting with
      Costal2/Fused complex through its C-terminal tail.
AB  - The Hedgehog (Hh) family of secreted proteins controls many aspects of growth and
      patterning in animal development. The seven-transmembrane protein Smoothened
      (Smo) transduces the Hh signal in both vertebrates and invertebrates; however,
      the mechanism of its action remains unknown. We found that Smo lacking its C
      terminal tail (C-tail) is inactive, whereas membrane-tethered Smo C-tail has
      constitutive albeit low levels of Hh signaling activity. Smo physically interacts
      with Costal2 (Cos2) and Fused (Fu) through its C-tail. Deletion of the Cos2/Fu
      binding domain from Smo abolishes its signaling activity. Moreover,
      overexpressing Cos2 mutants that fail to bind Fu and Ci but retain Smo-binding
      activity blocks Hh signaling. Taken together, our results suggest that Smo
      transduces the Hh signal by physically interacting with the Cos2/Fu protein
      complex.

PMID- 14597667
TI  - Resveratrol: from grapevines to mammalian biology.

PMID- 14597666
TI  - RhoB controls Akt trafficking and stage-specific survival of endothelial cells
      during vascular development.
AB  - Blood vessel formation is a complex morphological process that is only beginning
      to be understood at the molecular level. In this study, we demonstrate a novel
      and critical role for the small GTPase, RhoB, in vascular development. RhoB null
      mice have retarded vascular development in the retina characterized by altered
      sprout morphology. Moreover, pharmaceutical means to deplete RhoB in neonatal
      rats is associated with apoptosis in the sprouting endothelial cells of newly
      forming vessels. Similarly, acute depletion of RhoB by antisense or dominant
      negative strategies in primary endothelial cell culture models led to apoptosis
      and failures in tube formation. We identified a novel link between RhoB and the
      Akt survival signaling pathway to explain these changes. Confocal microscopy
      revealed that RhoB is highly localized to the nuclear margin with a small
      percentage found inside the nucleus. Similarly, total Akt is throughout the cell
      but has increased accumulation at the nuclear margin, and active phosphorylated
      Akt is found primarily inside the nucleoplasm, where it partially colocalizes
      with the RhoB therein. We show that this colocalization is functionally relevant,
      because when RhoB was depleted, Akt was excluded from the nucleus and total
      cellular Akt protein was decreased in a proteosome-dependent manner. Because the
      function of RhoB in vivo appears to only be rate limiting for endothelial cell
      sprouting, we propose that RhoB has a novel stage-specific function to regulate
      endothelial cell survival during vascular development. RhoB may offer a
      therapeutic target in diseases such as cancer, diabetic retinopathy, and macular
      degeneration, where the disruption of sprouting angiogenesis would be desirable.

PMID- 14597668
TI  - Cyclooxygenase-2 and 5-lipoxygenase converging functions on cell proliferation
      and tumor angiogenesis: implications for cancer therapy.
AB  - Cyclooxygenase (COX) and lipoxygenase (LO) metabolic pathways are emerging as key
      regulators of cell proliferation and neo-angiogenesis. COX and LO inhibitors are
      being investigated as potential anticancer drugs and results from clinical trials
      seem to be encouraging. In this article we will review evidence of COX-2 and 5-LO
      involvement in cancer pathobiology, propose a model of integrated control of cell
      proliferation by these enzymes, and discuss the pharmacologic implications of
      this model.

PMID- 14597669
TI  - Adaptive differences in the structure and macromolecular compositions of the air
      and water corneas of the "four-eyed" fish (Anableps anableps).
AB  - The water meniscus bisects the eyes of the "four-eyed" fish Anableps anableps,
      resulting in simultaneous vision in air and water. We compare the structure and
      macromolecular compositions of the Anableps dorsal (air) and ventral (water)
      corneas with the fully aquatic zebrafish cornea. The Anableps dorsal corneal
      epithelium is thicker (>20 cell layers), flatter (approximately 1.94 mm radius of
      curvature), and contains approximately 15-fold more glycogen (0.16 microg/microg
      water-soluble protein) than the ventral corneal epithelium (5-7 cell layers;
      approximately 1.63 mm radius of curvature; 0.01 microg glycogen/microg water
      soluble protein), which resembles the zebrafish corneal epithelium. Gelsolin is
      the major water-soluble protein in the zebrafish (approximately 50%) and Anableps
      dorsal (approximately 38%) and ventral (approximately 21%) corneal epithelia,
      suggesting that gelsolin was recruited for high corneal expression before these
      two species diverged at least 100 million years ago and that abundant corneal
      gelsolin is not limited to aquatic vision. Anableps gelsolin, deduced from its
      cDNA, is 57% identical to zebrafish gelsolin. Paucity of Anableps corneal F-actin
      (consistent with high gelsolin) was confirmed by the absence of rhodamine
      phalloidin staining. We suggest amphibious refraction and protection from UV
      irradiation and desiccation in air as selective constraints for the
      specializations of the Anableps dorsal cornea.

PMID- 14597670
TI  - Intrinsic versus microenvironmental regulation of lymphatic endothelial cell
      phenotype and function.
AB  - Vascular endothelial cells are characterized by a high degree of functional and
      phenotypic plasticity, which is controlled both by their pericellular
      microenvironment and their intracellular gene expression programs. To gain
      further insight into the mechanisms regulating the endothelial cell phenotype, we
      have compared the responses of lymphatic endothelial cells (LECs) and blood
      vascular endothelial cells (BECs) to vascular endothelial growth factors (VEGFs).
      VEGFR-3-specific signals are sufficient for LEC but not BEC proliferation, as
      shown by the ability of the specific ligand VEGF-C156S to stimulate cell cycle
      entry only in LECs. On the other hand, we found that VEGFR-3 stimulation did not
      induce LEC cell shape changes typical of VEGFR-2-stimulated LECs, indicating
      receptor-specific differences in the cytoskeletal responses. Genes induced via
      VEGFR-2 also differed between BECs and LECs: angiopoietin-2 (Ang-2) was induced
      via VEGFR-2 in BECs and LECs, but the smooth muscle cell (SMC) chemoattractant
      BMP-2 was induced only in BECs. Both BECs and LECs were able to promote SMC
      chemotaxis, but contact with SMCs led to down-regulation of VEGFR-3 expression in
      BECs in a 3-dimensional coculture system. This was consistent with the finding
      that VEGFR-3 is down-regulated in vivo at sites of endothelial cell
      pericyte/smooth muscle cell contacts. Collectively, these data show intrinsic
      cell-specific differences of BEC and LEC responses to VEGFs and identify a
      pericellular regulatory mechanism for VEGFR-3 down-regulation in endothelial
      cells.

PMID- 14597671
TI  - Disease-specific accumulation of mutant ubiquitin as a marker for proteasomal
      dysfunction in the brain.
AB  - Molecular misreading of the ubiquitin-B (UBB) gene results in a dinucleotide
      deletion in UBB mRNA. The resulting mutant protein, UBB+1, accumulates in the
      neuropathological hallmarks of Alzheimer disease. In vitro, UBB+1 inhibits
      proteasomal proteolysis, although it is also an ubiquitin fusion degradation
      substrate for the proteasome. Using the ligase chain reaction to detect
      dinucleotide deletions, we report here that UBB+1 transcripts are present in each
      neurodegenerative disease studied (tauo- and synucleinopathies) and even in
      control brain samples. In contrast to UBB+1 transcripts, UBB+1 protein
      accumulation in the ubiquitin-containing neuropathological hallmarks is
      restricted to the tauopathies such as Pick disease, frontotemporal dementia,
      progressive supranuclear palsy, and argyrophilic grain disease. Remarkably, UBB+1
      protein is not detected in the major forms of synucleinopathies (Lewy body
      disease and multiple system atrophy). The neurologically intact brain can cope
      with UBB+1 as lentivirally delivered UBB+1 protein is rapidly degraded in rat
      hippocampus, whereas the K29,48R mutant of UBB+1, which is not ubiquitinated, is
      abundantly expressed. The finding that UBB+1 protein only accumulates in
      tauopathies thus implies that the ubiquitin-proteasome system is impaired
      specifically in this group of neurodegenerative diseases and not in
      synucleinopathies and that the presence of UBB+1 protein reports proteasomal
      dysfunction in the brain.

PMID- 14597672
TI  - HIV-1 Nef triggers Vav-mediated signaling pathway leading to functional and
      morphological differentiation of dendritic cells.
AB  - The accessory HIV-1 Nef protein plays a key role in AIDS pathogenesis. We
      recently demonstrated that exogenous Nef triggers phenotypic and functional
      differentiation of immature dendritic cells (DCs). Here we investigated whether
      the Nef-induced DC differentiation occurs with morphological remodeling and have
      focused on the interference of Nef in the signaling pathways that regulates DC
      maturation. We found that exogenous Nef enters immature DCs, promoting their
      functional and morphological differentiation. Specifically, Nef promotes
      interleukin (IL) -12 release, which closely fits with nuclear factor (NF) -kappaB
      activation. Nef induces rearrangement of actin microfilaments, leading to uropod
      and ruffle formation. Moreover, Nef increases the capacity of DCs to form
      clusters with allogeneic CD4+ T cells, improving immunological synapse formation.
      Searching for molecules involved in Nef-triggered signaling pathways driving the
      DC maturation, we found that Nef targets Vav and promotes its tyrosine
      phosphorylation, associated with its nucleus-to-cytoplasm redistribution. This
      has a direct effect on Vav guanine nucleotide exchange factor activity for the
      small GTPase Rac1. We hypothesize that targeting Vav, Nef modulates both early
      signaling events (such as cytoskeletal rearrangement) and delayed responses (such
      as transcriptional regulation), promoting DC differentiation. Our results
      highlight how Nef may enhance T lymphocyte activation, thus fostering virus
      dissemination, manipulating the DC arm of the immune response.

PMID- 14597673
TI  - Epimorphin acts to induce hair follicle anagen in C57BL/6 mice.
AB  - Epimorphin is a mesenchymal morphogen that has been shown to mediate epithelial
      mesenchymal signaling interactions in various organs. We now show that epimorphin
      functions in hair follicle morphogenesis; using a novel ex vivo organ culture
      assay, we define a mechanism for epimorphin signaling that may provide insight
      into general developmental processes. We found that epimorphin was produced by
      follicular mesenchymal cells and bound selectively to follicular epithelial
      cells, and that treatment with recombinant epimorphin could stimulate procession
      of hair follicles from telogen (resting stage) to anagen (growing stage). Based
      on analyses of epimorphin proteolytic digests that suggested a smaller peptide
      might be able to substitute for the full-length epimorphin molecule, we
      determined that pep7, a 10-amino acid peptide, was capable of inducing telogen-to
      anagen transition both in the culture assay and in the mouse. That pep7 showed
      maximal activity only when modified with specific sulfhydryl-reactive reagents
      suggested that a particular structural conformation of the peptide was essential
      for activity; molecular dynamics studies were pursued to investigate the active
      peptide structure. These findings define a previously unknown morphogenic process
      in the hair follicle that may have applications to many other organs.

PMID- 14597674
TI  - Human homologue of Drosophila CNK interacts with Ras effector proteins Raf and
      Rlf.
AB  - Connector enhancer of KSR (CNK) is a multidomain protein that participates in Ras
      signaling in Drosophila eye development. In this report we identify the human
      homologue of CNK, termed CNK2A, and a truncated alternatively spliced variant,
      CNK2B. We characterize CNK2 phosphorylation, membrane localization, and
      interaction with Ras effector molecules. Our results show that MAPK signaling
      appears to play a role in the phosphorylation of CNK2 in vivo. CNK2 is found in
      both membrane and cytoplasmic fractions of the cell. In MDCK cells, full-length
      CNK2 is localized to the lateral plasma membrane. Consistent with previous
      reports, we show CNK2 interacts with Raf. CNK2 interaction was mapped to the
      regulatory and kinase domains of Raf, as well as to the carboxyl-terminal half of
      CNK2. CNK2 also interacts with the Ral signaling components, Ral GTPase, and the
      RalGDS family member Rlf. CNK2 interaction was mapped to the GEF domain of Rlf.
      The ability of CNK2 to interact with both Ras effector proteins Raf and Rlf
      suggests that CNK2 may integrate signals between MAPK and Ral pathways through a
      complex interplay of components.

PMID- 14597675
TI  - Differential regulation of in vivo angiogenesis by angiotensin II receptors.
AB  - Angiotensin II (ANG II), a key regulator of blood pressure and body fluid
      homeostasis, exerts mitogenic effects on endothelial cells. We therefore
      hypothesized that ANG II could be a mediator between homeostatic changes within
      the vascular perfusion bed and growth factor-driven angiogenesis. In the present
      study, we applied the alginate implant angiogenesis model in mice with normal ANG
      II levels, elevated ANG II levels by transgenic overexpression of angiotensinogen
      (AOGEN), or in AT2 receptor-deficient mice. We demonstrate that a decrease in the
      amount of circulating ANG II by the angiotensin-converting enzyme (ACE) inhibitor
      enalapril or the AT1 receptor antagonist losartan induced a stimulation of in
      vivo angiogenesis implying an inhibitory function of ANG II through the AT1
      receptor. However, the strong increase of angiogenesis in AOGEN-transgenic mice
      compared with mice with normal ANG II levels suggests additional stimulatory
      activity. We showed that the ANG II-induced stimulation of angiogenesis is linked
      to the AT2 receptor as an impaired induction of angiogenesis was obtained in AT2
      receptor knockout mice. These findings provide the first evidence that the AT2
      receptor mediates a stimulation of in vivo angiogenesis and indicate that ANG II
      is a humoral regulator of peripheral angiogenesis involving two receptor subtypes
      with opposing actions.

PMID- 14597676
TI  - Cellular growth inhibition by IGFBP-3 and TGF-beta1 requires LRP-1.
AB  - The type V TGF-beta receptor (TbetaR-V)/IGFBP-3 receptor mediates the IGF
      independent growth inhibition induced by IGFBP-3. It also mediates the growth
      inhibitory response to TGF-beta1 in concert with other TGF-beta receptor types,
      and its loss may contribute to the malignant phenotype of human carcinoma cells.
      Here we demonstrate that TbetaR-V is identical to LRP-1/alpha2M receptor as shown
      by MALDI-TOF analysis of tryptic peptides of TbetaR-V purified from bovine liver.
      In addition, 125I-IGFBP-3 affinity-labeled TbetaR-V in Mv1Lu cells is
      immunoprecipitated by antibodies to LRP-1 and TbetaR-V. RAP, an LRP-1 antagonist,
      inhibits binding of 125I-TGF-beta1 and 125I-IGFBP-3 to TbetaR-V and diminishes
      IGFBP-3-induced growth inhibition in Mv1Lu cells. Absent or low levels of LRP-1,
      as with TbetaR-V, have been linked to the malignant phenotype of carcinoma cells.
      Mutagenized Mv1Lu cells selected for reduced expression of LRP-1 have an
      attenuated growth inhibitory response to TGF-beta1 and IGFBP-3. LRP-1-deficient
      mouse embryonic fibroblasts lack a growth inhibitory response to TGF-beta1 and
      IGFBP-3. On the other hand, stable transfection of H1299 human lung carcinoma
      cells with LRP-1 cDNA restores the growth inhibitory response. These results
      suggest that the LRP-1/TbetaR-V/IGFBP-3 receptor is required for the growth
      inhibitory response to IGFBP-3 and TGF-beta1.

PMID- 14597677
TI  - Imatinib induces mitochondria-dependent apoptosis of the Bcr-Abl-positive K562
      cell line and its differentiation toward the erythroid lineage.

PMID- 14597678
TI  - Somatoform disorders in DSM-V.

PMID- 14597679
TI  - Guidelines for conducting a psychiatric evaluation of the unrelated kidney donor.
AB  - Living unrelated kidney donors have been increasingly sought out as potential
      resources for patients with end-stage renal disease. Several psychiatric issues
      must be factored into the presurgical evaluation of prospective donors. This
      paper describes a proposed guideline intended to assist clinicians in the
      psychiatric evaluation of prospective kidney donors. Topics covered in the
      interview include the prospective donor's stability and ability to make an
      informed decision, the donor's understanding of the recipient's illness and of
      the transplant surgery, and extenuating factors that may influence the decision
      to donate. While efficient and thorough, the guideline is intended to be flexible
      enough to address the variety of issues that can affect the prospective donor's
      decision to pursue surgery.

PMID- 14597680
TI  - Relationship of self-perceptions of memory and worry to objective measures of
      memory and cognition in the general population.
AB  - This investigation compared how perceived memory ability or level of worry about
      memory related to performance on objective tests of memory and cognition. Data
      from 1,488 participants from the Baltimore cohort of the Epidemiologic Catchment
      Area study were analyzed. Significant associations were found between self
      ratings of memory and each of four objective measures of cognitive functioning.
      Memory worry was associated with worse delayed recall but not with worse word
      recognition, lower current Mini-Mental State Examination (MMSE) score, or greater
      change in MMSE score over time. Individuals experiencing changes in cognitive
      function appear to have some awareness of their condition, and a simple probe of
      a person's perception of memory in the context of a general medical evaluation
      may help identify those who need further assessment.

PMID- 14597682
TI  - Somatic, posttraumatic stress, and depressive symptoms among injured patients
      treated in trauma surgery.
AB  - Few investigations have examined the course of somatic complaints among acutely
      injured trauma survivors. Posttraumatic stress disorder (PTSD), depressive, and
      somatic symptoms were assessed in trauma surgery inpatients (N=73) interviewed
      while hospitalized and again 12 months after their injury. Somatic symptoms
      occurred frequently and were significantly greater in patients with higher levels
      of PTSD and depressive symptoms, even after the analyses were adjusted for injury
      severity and medical comorbidity. These findings, when considered in conjunction
      with data documenting the heterogeneity of treatment providers visited after
      traumatic injury, suggest that the development of early screening and
      intervention procedures should incorporate assessments of physical symptoms.

PMID- 14597681
TI  - Somatic symptoms in primary care: etiology and outcome.
AB  - Although somatic complaints are the predominant reason for seeking general
      medical care, their etiology and prognosis remain poorly understood. In a random
      sample of the records of all patients visiting an urban primary care clinic
      during four 1-month periods, 289 patients had one or more somatic symptoms, a
      total of 433 symptoms. Using explicit criteria, physician raters classified
      nearly half (48%) of the symptoms as either psychiatric or idiopathic in
      etiology. Reviewing follow-up notes for 12 months after the index visit, raters
      found that at least one-fourth of the symptoms persisted. Independent predictors
      of symptom persistence were prior visits for the same symptom, symptom type
      (i.e., headache or back pain), male gender, and greater medical comorbidity
      (i.e., seven or more medical diagnoses). Developing better management strategies
      for prevalent, medically unexplained, persistent somatic symptoms is a health
      care priority.

PMID- 14597683
TI  - Meaning of illness and psychological adjustment to HIV/AIDS.
AB  - The authors explored the relationship between meaning of illness and
      psychological adjustment in persons with symptomatic HIV disease and AIDS. A
      group of 203 participants completed self-report questionnaires measuring meaning
      of illness, problem-focused coping, social support, psychological well-being, and
      depressed mood. Positive meaning was associated with a higher level of
      psychological well-being and a lower level of depressed mood. Further, meaning
      contributed significantly to predicting both psychological well-being and
      depressed mood over and above the contributions of problem-focused coping and
      social support. These findings have implications for HIV coping and adjustment
      models and for HIV-related psychotherapy.

PMID- 14597684
TI  - A new approach to the assessment of the treatment effects of somatoform
      disorders.
AB  - A new 53-item instrument for the evaluation of treatment effects in somatoform
      disorders, the Screening for Somatoform Symptoms-7 (SOMS-7), is presented. It
      covers all somatic symptoms mentioned as occurring in somatization disorder,
      according to DSM-IV and ICD-10. A group of 325 patients was assessed at the
      beginning and end of treatment to compute scores of reliability and validity. The
      new scale showed high internal consistency (alpha=0.92) and revealed two
      composite indices: somatization symptom count and somatization severity index.
      These indices discriminated patients fulfilling complete criteria for somatoform
      disorders, patients with somatization syndrome, and patients with other mental
      and psychosomatic disorders. The instrument confirmed symptom reductions between
      admission and discharge, while in another group composed of wait-listed patients,
      no significant decrease in symptoms was observed. In sum, the SOMS-7 seems to be
      a comprehensive, reliable, and valid instrument for the evaluation of treatment
      effects in patients with somatoform disorders.

PMID- 14597685
TI  - A systematic review of studies of the cost-effectiveness of mental health
      consultation-liaison interventions in general hospitals.
AB  - A systematic review of cost-effectiveness analyses of mental health consultation
      liaison interventions in general hospitals was conducted. Few studies have
      evaluated the cost-effectiveness of consultation-liaison interventions, and only
      two articles met the criteria for inclusion in the review. The comparable
      variable was length of the hospital stay. It could not be concluded that
      psychiatric consultation had an effect on the duration of hospital stays. In one
      of the studies, the group that received psychiatric consultation showed
      improvement in depressive symptoms. Additional studies would have been relevant
      to this review if they had replicated clinical practice by using a naturalistic
      research design.

PMID- 14597687
TI  - Medical complications of catatonia: a case of catatonia-induced deep venous
      thrombosis.

PMID- 14597686
TI  - Ephedrine-type alkaloid-containing dietary supplements and substance dependence.

PMID- 14597688
TI  - Pharmacokinetic drug interactions of morphine, codeine, and their derivatives:
      theory and clinical reality, Part II.
AB  - Pharmacokinetic drug-drug interactions with codeine, dihydrocodeine, hydrocodone,
      oxycodone, and buprenorphine are reviewed in this column. These compounds have a
      very similar chemical structure to morphine. Unlike morphine, which is
      metabolized chiefly through conjugation reactions with uridine diphosphate
      glucuronosyl transferase (UGT) enzymes, these five drugs are metabolized both
      through oxidative reactions by the cytochrome P450 (CYP450) enzyme and
      conjugation by UGT enzymes. There is controversy as to whether codeine,
      dihydrocodeine, and hydrocodone are actually prodrugs requiring activation by the
      CYP450 2D6 enzyme or UGT enzymes. Oxycodone and buprenorphine, however, are
      clearly not prodrugs and are metabolized by the CYP450 2D6 and 3A4 enzymes,
      respectively. Knowledge of this metabolism assists in the understanding for the
      potential of drug-drug interactions with these drugs. This understanding is
      important so that clinicians can choose the proper dosages for analgesia and
      anticipate potential drug-drug interactions.

PMID- 14597689
TI  - Tuberous sclerosis with psychosis.

PMID- 14597690
TI  - QTc prolongation: possible association with risperidone and/or haloperidol.

PMID- 14597691
TI  - Trauma in a nurse after patient suicide.

PMID- 14597692
TI  - Benzodiazepine exposure and history of trauma.

PMID- 14597693
TI  - Safety of the treatment of interferon-alpha-induced depression.

PMID- 14597695
TI  - SecA-dependent quality control of intracellular protein localization.
AB  - Complex secretion machineries mediate protein translocation across cellular
      membranes. These machines typically recognize their substrates via signal
      sequences, which are required for proper targeting to the translocon. We report
      that during posttranslational secretion the widely conserved targeting factor
      SecA performs a quality-control function that is based on a general chaperone
      activity. This quality-control mechanism involves assisted folding of signal
      sequenceless proteins, thereby excluding them from the secretion process. These
      results suggest that SecA channels proteins into one of two key pathways,
      posttranslational secretion or folding in the cytoplasm. Implications of this
      finding for intracellular protein localization are discussed.

PMID- 14597696
TI  - Multipoint linkage-disequilibrium mapping narrows location interval and
      identifies mutation heterogeneity.
AB  - Single-nucleotide polymorphism (SNP) genotypes were recently examined in an 890
      kb region flanking the human gene CYP2D6. Single-marker and haplotype-based
      analyses identified, with genomewide significance (P < 10-7), a 403-kb interval
      displaying strong linkage disequilibrium (LD) with predicted poor-metabolizer
      phenotype. However, the width of this interval makes the location of causal
      variants difficult: for example, the interval contains seven known or predicted
      genes in addition to CYP2D6. We have developed the Bayesian fine-mapping software
      coldmap, which, applied to these genotype data, yields a 95% location interval
      covering only 185 kb and establishes genomewide significance for a causal locus
      within the region. Strikingly, our interval correctly excludes four SNPs, which
      individually display association with genomewide significance, including the SNP
      showing strongest LD (P < 10-34). In addition, coldmap distinguishes homozygous
      cases for the major CYP2D6 mutation from those bearing minor mutations. We
      further investigate a selection of SNP subsets and find that previously reported
      methods lead to a 38% savings in SNPs at the cost of an increase of <20% in the
      width of the location interval.

PMID- 14597697
TI  - Spx-dependent global transcriptional control is induced by thiol-specific
      oxidative stress in Bacillus subtilis.
AB  - The Spx protein of Bacillus subtilis represses activator-stimulated transcription
      by interacting with the C-terminal domain of RNA polymerase (RNAP) alpha subunit.
      Its concentration increases in cells lacking the ATP-dependent protease, ClpXP,
      resulting in severe effects on growth and developmental processes. Microarray
      analysis was undertaken to identify genes that are induced or repressed when Spx
      interacts with RNAP. The induced genes included those encoding products known to
      function in maintaining thiol homeostasis. Two genes, thioredoxin (trxA) and
      thioredoxin reductase (trxB), are transcriptionally induced under conditions of
      thiol-specific oxidative (disulfide) stress by a mechanism involving Spx-RNAP
      interaction. Disulfide stress also results in an increase in Spx-dependent
      transcriptional repression. The increase in Spx activity in cells encountering
      disulfide stress is due in part to a posttranscriptional mechanism of spx control
      resulting in an increase in Spx concentration. An spx null mutant and a strain
      bearing an allele of rpoA that prevents Spx-RNAP interaction show
      hypersensitivity to disulfide stress. From these results, it is proposed that Spx
      is an activator that mobilizes the operations necessary to reverse the effects of
      oxidative damage, but it also serves as a negative regulator that causes the
      postponement of developmental programs and energy-consuming growth-related
      functions while the cell copes with the period of stress.

PMID- 14597698
TI  - Conscious and subliminal conflicts in normal subjects and patients with
      schizophrenia: the role of the anterior cingulate.
AB  - The human anterior cingulate cortex (ACC), which is active during conflict
      monitoring tasks, is thought to participate with prefrontal cortices in a
      distributed network for conscious self-regulation. This hypothesis predicts that
      conflict-related ACC activation should occur only when the conflicting stimuli
      are consciously perceived. To dissociate conflict from consciousness, we measured
      the behavioral and brain imaging correlates of a motor conflict induced by task
      irrelevant subliminal or conscious primes. The same task was studied in normal
      subjects and in patients with schizophrenia in whom the ACC and prefrontal cortex
      are thought to be dysfunctional. Conscious, but not subliminal, conflict affected
      anterior cingulate activity in normal subjects. Furthermore, patients with
      schizophrenia, who exhibited a hypoactivation of the ACC and other frontal,
      temporal, hippocampal, and striatal sites, showed impaired conscious priming but
      normal subliminal priming. Those findings suggest that subliminal conflicts are
      resolved without ACC contribution and that the ACC participates in a distributed
      conscious control network that is altered in schizophrenia.

PMID- 14597699
TI  - NADPH oxidase and extracellular regulated kinases 1/2 are targets of prion
      protein signaling in neuronal and nonneuronal cells.
AB  - Putative functions of the cellular prion protein, PrPC, include resistance to
      oxidative stress, copper uptake, cell adhesion, and cell signaling. Here, we
      report NADPH oxidase-dependent reactive oxygen species (ROS) production and
      extracellular regulated kinases 1/2 (ERK1/2) phosphorylation on PrPC stimulation
      in the 1C11 neuroectodermal precursor, in its neuronal differentiated progenies,
      and in GT1-7 neurohypothalamic and BW5147 lymphoid cells. In neuroprogenitor,
      hypothalamic, and lymphoid cells, ERK1/2 activation is fully controlled by the
      NADPH oxidase-dependent ROS production. In 1C11-derived bioaminergic cells, ROS
      signaling and ERK1/2 phosphorylation are both controlled by Fyn kinase
      activation, introducing some specificity in PrPC transduction associated with
      this neuronal context. These data argue for an ubiquitous function of PrPC in
      cell-redox homeostasis through ROS production.

PMID- 14597700
TI  - Aquaporin-4 square array assembly: opposing actions of M1 and M23 isoforms.
AB  - Osmotic homeostasis in the brain involves movement of water through aquaporin-4
      (AQP4) membrane channels. Perivascular astrocyte end-feet contain distinctive
      orthogonal lattices (square arrays) assembled from 4- to 6-nm intramembrane
      particles (IMPs) corresponding to individual AQP4 tetramers. Two isoforms of AQP4
      result from translation initiation at methionine residues M1 and M23, but no
      functional differences are known. In this study, Chinese hamster ovary cells were
      transfected with M1, M23, or M1+M23 isoforms, and AQP4 expression was confirmed
      by immunoblotting, immunocytochemistry, and immunogold labeling. Square array
      organization was examined by freeze-fracture electron microscopy. In astrocyte
      end-feet, >90% of 4- to 6-nm IMPs were found in square arrays, with 65% in arrays
      of 13-30 IMPs. In cells transfected with M23, 95% of 4- to 6-nm IMPs were in
      large assemblies (rafts), 85% of which contained >100 IMPs. However, in M1 cells,
      >95% of 4- to 6-nm IMPs were present as singlets, with <5% in incipient arrays of
      2-12 IMPs. In M1+M23 cells, 4- to 6-nm IMPs were in arrays of intermediate sizes,
      resembling square arrays in astrocytes. Structural cross-bridges of 1 x 2 nm
      linked >90% of IMPs in M23 arrays ( approximately 1,000 cross-bridges per
      microm2) but were rarely seen in M1 cells. These studies show that M23 and M1
      isoforms have opposing effects on intramembrane organization of AQP4: M23 forms
      large square arrays with abundant cross-bridges; M1 restricts square array
      assembly.

PMID- 14597702
TI  - Subadult experience influences adult mate choice in an arthropod: exposed female
      wolf spiders prefer males of a familiar phenotype.
AB  - Current sexual selection theory proposes several potential mechanisms driving the
      evolution of female mating preferences, few of which involve social interactions.
      Although vertebrate examples of socially influenced mating preferences do exist,
      the invertebrate examples are virtually nonexistent. Here I demonstrate that the
      mating preferences of female wolf spiders can be acquired through exposure as
      subadults to unrelated, sexually active adult males. I first conducted exposure
      trials during which subadult females of the wolf spider Schizocosa uetzi were
      allowed to interact with mature males of an experimentally manipulated phenotype
      (either black or brown forelegs). After maturation, these previously exposed
      females were paired with a male of either a familiar or unfamiliar manipulated
      phenotype for mate-choice trials. Subadult females that were exposed to directed
      courtship by mature males of a particular morphological phenotype were
      subsequently more likely to mate with a male of a familiar phenotype as adults.
      Furthermore, females that were exposed as subadults were more likely, as adults,
      to cannibalize a courting male with an unfamiliar phenotype. Unexposed females
      did not distinguish between phenotypes in either mate choice or cannibalism
      frequency. These results suggest a previously uncharacterized mechanism
      influencing the origin of female mating preferences and ultimately the evolution
      of male traits: subadult experience. This study also stresses the potential
      importance of learning and memory on adult mate choice in an arthropod.

PMID- 14597701
TI  - An endogenous suppressor of hairy-wing insulator separates regulatory domains in
      Drosophila.
AB  - Insulators define independent domains of gene function throughout the genome. The
      Drosophila gypsy insulator was isolated from the gypsy retrotransposon as a
      region that contains a cluster of binding sites for the Suppressor of Hairy-wing
      [Su(Hw)] protein. To study the effects of the gypsy insulator on gene expression
      within a single genomic domain, targeted gene replacement was used to exchange
      the endogenous yellow gene, located at cytological location 1A, with a set of
      gypsy-modified yellow genes. Replaced yellow genes carried a gypsy insulator
      positioned between the yellow promoter and either the upstream or the downstream
      tissue-specific enhancers. Whereas the gypsy insulator blocked the function of
      the upstream enhancers at the endogenous location, the downstream enhancers were
      not blocked. Investigation of the 1A region revealed two clustered Su(Hw)-binding
      sites downstream of the yellow gene, named 1A-2, that bind Su(Hw) in vivo and
      possess enhancer blocking function. We propose that interaction between 1A-2 and
      the gypsy insulator permits activation of yellow expression by enhancers in the
      neighboring achaete-scute complex, causing an apparent absence of the block of
      the downstream yellow enhancers. Based on these data, we suggest that 1A-2 is an
      endogenous Su(Hw) insulator that separates regulatory domains within the
      Drosophila genome.

PMID- 14597704
TI  - Delayed K+ clearance associated with aquaporin-4 mislocalization: phenotypic
      defects in brains of alpha-syntrophin-null mice.
AB  - Recovery from neuronal activation requires rapid clearance of potassium ions (K+)
      and restoration of osmotic equilibrium. The predominant water channel protein in
      brain, aquaporin-4 (AQP4), is concentrated in the astrocyte end-feet membranes
      adjacent to blood vessels in neocortex and cerebellum by association with alpha
      syntrophin protein. Although AQP4 has been implicated in the pathogenesis of
      brain edema, its functions in normal brain physiology are uncertain. In this
      study, we used immunogold electron microscopy to compare hippocampus of WT and
      alpha-syntrophin-null mice (alpha-Syn-/-). We found that <10% of AQP4 immunogold
      labeling is retained in the perivascular astrocyte end-feet membranes of the
      alpha-Syn-/- mice, whereas labeling of the inwardly rectifying K+ channel,
      Kir4.1, is largely unchanged. Activity-dependent changes in K+ clearance were
      studied in hippocampal slices to test whether AQP4 and K+ channels work in
      concert to achieve isosmotic clearance of K+ after neuronal activation.
      Microelectrode recordings of extracellular K+ ([K+]o) from the target zones of
      Schaffer collaterals and perforant path were obtained after 5-, 10-, and 20-Hz
      orthodromic stimulations. K+ clearance was prolonged up to 2-fold in alpha-Syn-/-
      mice compared with WT mice. Furthermore, the intensity of hyperthermia-induced
      epileptic seizures was increased in approximately half of the alpha-Syn-/-mice.
      These studies lead us to propose that water flux through perivascular AQP4 is
      needed to sustain efficient removal of K+ after neuronal activation.

PMID- 14597705
TI  - Cytochrome P450 flexibility.

PMID- 14597703
TI  - Reciprocal modulation of phospholipase Cbeta isoforms: adaptation to chronic
      morphine.
AB  - Phosphoinositide turnover and calcium mobilization are fundamental determinants
      of acute and chronic opioid effects. Phosphoinositide-specific phospholipase C
      (PLC) are key signaling enzymes that play a pivotal role in mediating opioid
      modulation of inositol trisphosphate production and cytosolic calcium
      distribution, substrates for many acute and chronic opioid effects. Notably,
      phosphorylation of the beta isoforms of PLC, by kinases that are up-regulated
      after chronic morphine, is a potent modality for their regulation. Direct
      assessment of PLCbeta1 and PLCbeta3 phosphorylation in the guinea pig
      longitudinal muscle myenteric plexus tissue revealed substantial alterations
      after the induction of opioid tolerance. Notably, the direction of this
      modulation is isoform-specific. Phosphorylation of PLCbeta1 is significantly
      reduced, whereas that of PLCbeta3 is substantially augmented, changes not
      accompanied by altered content of PLCbeta1 or PLCbeta3 protein. In contrast to
      chronic morphine, acute morphine treatment of opioid naive longitudinal muscle
      myenteric plexus tissue attenuates PLCbeta3 phosphorylation, an effect also
      manifested by endogenous opioids that is reflected by the ability of acute
      naloxone to substantially augment PLCbeta3 phosphorylation. This indicates that
      PLCbeta phosphorylation is dynamically regulated. PLCbeta1 and PLCbeta3
      activities are negatively modulated by phosphorylation. Thus, their concomitant
      reciprocal phosphorylation would alter the relative contribution of these
      isoforms to PLC/Ca2+ signaling, a significant shift in light of their
      differential regulatory characteristics. Reciprocal modulation of the
      phosphorylation (activity) of two isoforms within the same subclass of signaling
      enzyme, proteins that have a high degree of structural similarity and subserve
      the same biological function, represents an adaptation modality to chronic
      morphine that has heretofore not been recognized.

PMID- 14597706
TI  - DNA replication of mitotic chromatin in Xenopus egg extracts.
AB  - Prereplication complexes are assembled at eukaryotic origins of DNA replication
      in the G1 phase of the cell cycle, and they are activated in S phase by cyclin
      dependent kinase (Cdk)2/cyclin E and Cdk2/cyclin A. Previous experiments using
      Xenopus nuclear assembly egg extracts suggested that Cdk1/cyclin A, which is
      normally active in early mitosis, can replace the function of Cdk2 in driving DNA
      replication, whereas Cdk1/cyclin B, which functions later in mitosis, cannot.
      Here, we use a completely soluble replication system derived from Xenopus egg
      extracts to show that Cdk1/cyclin B also can support DNA replication. The ability
      of mitotic Cdks to drive DNA replication raises the question of whether DNA
      replication is possible in mitosis. To address this question, chromatin
      containing prereplication complexes was driven into mitosis with Cdk1/cyclin B.
      Strikingly, upon addition of a replication extract, the chromatin underwent a
      complete round of DNA replication. Replicating mitotic chromosomes became visibly
      decondensed, and, after DNA replication was complete, they recondensed. Our
      results indicate that there is extensive overlap in the substrate specificity of
      the major metazoan Cdk/cyclin complexes and that mitosis is not fundamentally
      incompatible with DNA replication. The results suggest that origins that fail to
      initiate DNA replication in S phase might still be able to do so in mitosis.

PMID- 14597707
TI  - Histone modifications: Now summoning sumoylation.

PMID- 14597708
TI  - Biography of John Bongaarts.

PMID- 14597709
TI  - Biographies of newly elected Academy members.

PMID- 14597710
TI  - Exploring the origins of binding specificity through the computational redesign
      of calmodulin.
AB  - Calmodulin (CaM) is a second messenger protein that has evolved to bind tightly
      to a variety of targets and, as such, exhibits low binding specificity. We
      redesigned CaM by using a computational protein design algorithm to improve its
      binding specificity for one of its targets, smooth muscle myosin light chain
      kinase (smMLCK). Residues in or near the CaM/smMLCK binding interface were
      optimized; CaM interactions with alternative targets were not directly considered
      in the optimization. The predicted CaM sequences were constructed and tested for
      binding to a set of eight targets including smMLCK. The best CaM variant,
      obtained from a calculation that emphasized intermolecular interactions, showed
      up to a 155-fold increase in binding specificity. The increase in binding
      specificity was not due to improved binding to smMLCK, but due to decreased
      binding to the alternative targets. This finding is consistent with the fact that
      the sequence of wild-type CaM is nearly optimal for interactions with numerous
      targets.

PMID- 14597711
TI  - Neural correlates of training-related memory improvement in adulthood and aging.
AB  - Cognitive studies show that both younger and older adults can increase their
      memory performance after training in using a visuospatial mnemonic, although age
      related memory deficits tend to be magnified rather than reduced after training.
      Little is known about the changes in functional brain activity that accompany
      training-induced memory enhancement, and whether age-related activity changes are
      associated with the size of training-related gains. Here, we demonstrate that
      younger adults show increased activity during memory encoding in occipito
      parietal and frontal brain regions after learning the mnemonic. Older adults did
      not show increased frontal activity, and only those elderly persons who benefited
      from the mnemonic showed increased occipito-parietal activity. These findings
      suggest that age-related differences in cognitive reserve capacity may reflect
      both a frontal processing deficiency and a posterior production deficiency.

PMID- 14597712
TI  - Discovery of a bacterium, with distinctive dioxygenase, that is responsible for
      in situ biodegradation in contaminated sediment.
AB  - Microorganisms maintain the biosphere by catalyzing biogeochemical processes,
      including biodegradation of organic chemical pollutants. Yet seldom have the
      responsible agents and their respective genes been identified. Here we used field
      based stable isotopic probing (SIP) to discover a group of bacteria responsible
      for in situ metabolism of an environmental pollutant, naphthalene. We released
      13C-labeled naphthalene in a contaminated study site to trace the flow of
      pollutant carbon into the naturally occurring microbial community. Using GC/MS,
      molecular biology, and classical microbiological techniques we documented 13CO2
      evolution (2.3% of the dose in 8 h), created a library of 16S rRNA gene clones
      from 13C labeled sediment DNA, identified a taxonomic cluster (92 of 95 clones)
      from the microbial community involved in metabolism of the added naphthalene, and
      isolated a previously undescribed bacterium (strain CJ2) from site sediment whose
      16S rRNA gene matched that of the dominant member (48%) of the clone library.
      Strain CJ2 is a beta proteobacterium closely related to Polaromonas vacuolata.
      Moreover, strain CJ2 hosts the sequence of a naphthalene dioxygenase gene,
      prevalent in site sediment, detected before only in environmental DNA. This
      investigative strategy may have general application for elucidating the bases of
      many biogeochemical processes, hence for advancing knowledge and management of
      ecological and industrial systems that rely on microorganisms.

PMID- 14597713
TI  - Refractory nature of normal human diploid fibroblasts with respect to oncogene
      mediated transformation.
AB  - Human cells are known to be more refractory than rodent cells against oncogenic
      transformation in vitro. To date, the molecular mechanisms underlying such
      resistance remain largely unknown. The combination of simian virus 40 early
      region and H-Ras V12 has been effective for transformation of rat embryo
      fibroblasts, but not for human cells. However, the additional ectopic expression
      of the telomerase catalytic subunit (hTERT) was reported to be capable of causing
      transformation of normal human cells. In this study, however, we demonstrate that
      the combined expression of the above-mentioned three genetic elements is not
      always sufficient to transform normal human diploid fibroblasts (HDF). Although
      the expression and function of these introduced genetic elements were essentially
      the same, among four HDF, TIG-1 and TIG-3 were resistant to transformation. The
      other two (BJ and IMR-90) showed transformed phenotypes, but they were much
      restricted compared with rat embryo fibroblasts in expressing simian virus 40
      early region and H-Ras V12. In correlation with these phenotypes, TIG-1 and TIG-3
      remained diploid after the introduction of these genetic elements, whereas BJ and
      IMR-90 became highly aneuploid. These results strongly suggest that the lack of
      telomerase is not the sole reason for the refractory nature of HDF against
      transformation and that normal human cells have still undefined intrinsic
      mechanisms rendering them resistant to oncogenic transformation.

PMID- 14597714
TI  - Adaptive evolution in the Arabidopsis MADS-box gene family inferred from its
      complete resolved phylogeny.
AB  - Gene duplication is a substrate of evolution. However, the relative importance of
      positive selection versus relaxation of constraints in the functional divergence
      of gene copies is still under debate. Plant MADS-box genes encode transcriptional
      regulators key in various aspects of development and have undergone extensive
      duplications to form a large family. We recovered 104 MADS sequences from the
      Arabidopsis genome. Bayesian phylogenetic trees recover type II lineage as a
      monophyletic group and resolve a branching sequence of monophyletic groups within
      this lineage. The type I lineage is comprised of several divergent groups.
      However, contrasting gene structure and patterns of chromosomal distribution
      between type I and II sequences suggest that they had different evolutionary
      histories and support the placement of the root of the gene family between these
      two groups. Site-specific and site-branch analyses of positive Darwinian
      selection (PDS) suggest that different selection regimes could have affected the
      evolution of these lineages. We found evidence for PDS along the branch leading
      to flowering time genes that have a direct impact on plant fitness. Sites with
      high probabilities of having been under PDS were found in the MADS and K domains,
      suggesting that these played important roles in the acquisition of novel
      functions during MADS-box diversification. Detected sites are targets for further
      experimental analyses. We argue that adaptive changes in MADS-domain protein
      sequences have been important for their functional divergence, suggesting that
      changes within coding regions of transcriptional regulators have influenced
      phenotypic evolution of plants.

PMID- 14597715
TI  - The inhibitory potential of Fc receptor homolog 4 on memory B cells.
AB  - Fc receptor homolog 4 (FcRH4) is a B cell-specific member of the recently
      identified family of FcRHs whose intracellular domain contains three potential
      immunoreceptor tyrosine-based inhibitory motifs (ITIMs). The signaling potential
      of this receptor, shown here to be preferentially expressed by memory B cells,
      was compared with the inhibitory receptor FcgammaRIIb in B cells expressing
      either WT FcgammaRIIb or chimeric proteins in which the intracellular domain of
      FcRH4 was fused to the transmembrane and extracellular domains of FcgammaRIIb.
      Coligation of the FcgammaRIIb/FcRH4 chimeric protein with the B cell receptor
      (BCR) led to tyrosine phosphorylation of the two membrane-distal tyrosines and
      profound inhibition of BCR-mediated calcium mobilization, whole cell tyrosine
      phosphorylation, and mitogen-activated protein (MAP)-kinase activation.
      Mutational analysis of the FcRH4 cytoplasmic region indicated that the two
      membrane-distal ITIMs are essential for this inhibitory potential.
      Phosphopeptides corresponding to these ITIMs could bind the Src homology 2 (SH2)
      domain-containing tyrosine phosphatases SHP-1 and SHP-2, which associated with
      the WT FcRH4 and with mutants having inhibitory capability. These findings
      indicate the potential for FcRH4 to abort B cell receptor signaling by recruiting
      SHP-1 and SHP-2 to its two membrane distal ITIMs.

PMID- 14597716
TI  - A proatherogenic role for cGMP-dependent protein kinase in vascular smooth muscle
      cells.
AB  - Nitric oxide (NO) exerts both antiatherogenic and proatherogenic effects, but the
      cellular and molecular mechanisms that contribute to modulation of
      atherosclerosis by NO are not understood completely. The cGMP-dependent protein
      kinase I (cGKI) is a potential mediator of NO signaling in vascular smooth muscle
      cells (SMCs). Postnatal ablation of cGKI selectively in the SMCs of mice reduced
      atherosclerotic lesion area, demonstrating that smooth muscle cGKI promotes
      atherogenesis. Cell-fate mapping indicated that cGKI is involved in the
      development of SMC-derived plaque cells. Activation of endogenous cGKI in primary
      aortic SMCs resulted in cells with increased levels of proliferation; increased
      levels of vascular cell adhesion molecule-1, peroxisome proliferator-activated
      receptor gamma, and phosphatidylinositol 3-kinase/Akt signaling; and decreased
      plasminogen activator inhibitor 1 mRNA, which all are potentially proatherogenic
      properties. Taken together, these results highlight the pathophysiologic
      significance of vascular SMCs in atherogenesis and identify a key role for cGKI
      in the development of atherogenic SMCs in vitro and in vivo. We suggest that
      activation of smooth muscle cGKI contributes to the proatherogenic effect of NO
      and that inhibition of cGKI might be a therapeutic option for treating
      atherosclerosis in humans.

PMID- 14597717
TI  - Critical roles for IFN-beta in lymphoid development, myelopoiesis, and tumor
      development: links to tumor necrosis factor alpha.
AB  - We have generated mice null for IFN-beta and report the diverse consequences of
      IFN-beta for both the innate and adaptive arms of immunity. Despite no
      abnormalities in the proportional balance of CD4 and CD8 T cell populations in
      the peripheral blood, thymus, and spleen of IFN-beta-/- mice, activated lymph
      node and splenic T lymphocytes exhibit enhanced T cell proliferation and
      decreased tumor necrosis factor alpha production, relative to IFN-beta+/+ mice.
      Notably, constitutive and induced expression of tumor necrosis factor alpha is
      reduced in the spleen and bone marrow (BM) macrophages, respectively, of IFN-beta
      /- mice. We also observe an altered splenic architecture in IFN-beta-/- mice and
      a reduction in resident macrophages. We identify a potential defect in B cell
      maturation in IFN-beta-/- mice, associated with a decrease in B220+ve/high/CD43
      ve BM-derived cells and a reduction in BP-1, IgM, and CD23 expression.
      Circulating IgM-, Mac-1-, and Gr-1-positive cells are also substantially
      decreased in IFN-beta-/- mice. The decrease in the numbers of circulating
      macrophages and granulocytes likely reflects defective maturation of primitive BM
      hematopoiesis in mice, shown by the reduction of colony-forming units,
      granulocyte-macrophage. We proceeded to evaluate the in vivo growth of malignant
      cells in the IFN-beta-/- background and give evidence that Lewis lung carcinoma
      specific tumor growth is more aggressive in IFN-beta-/- mice. Taken altogether,
      our data suggest that, in addition to the direct growth-inhibitory effects on
      tumor cells, IFN-beta is required during different stages of maturation in the
      development of the immune system.

PMID- 14597718
TI  - Endosomal compartmentalization in three dimensions: implications for membrane
      fusion.
AB  - Endosomes are major sorting stations in the endocytic route that send proteins
      and lipids to multiple destinations in the cell, including the cell surface,
      Golgi complex, and lysosomes. They have an intricate architecture of internal
      membrane structures enclosed by an outer membrane. Recycling proteins remain on
      the outer membrane, whereas proteins that are destined for degradation in the
      lysosome are sorted to the interior. Recently, a retrograde pathway was
      discovered whereby molecules, like MHC class II of the immune system, return from
      the internal structures to the outer membrane, allowing their further transport
      to the cell surface for T cell activation. Whether this return involves back
      fusion of free vesicles with the outer membrane, or occurs via the continuity of
      the two membrane domains, is an unanswered question. By electron tomography of
      cryo-immobilized cells we now demonstrate that, in multivesicular endosomes of B
      lymphocytes and dendritic cells, the inner membranes are free vesicles. Hence,
      protein transport from inner to outer membranes cannot occur laterally in the
      plane of the membrane, but requires fusion between the two membrane domains. This
      implies the existence of an intracellular machinery that mediates fusion between
      the exoplasmic leaflets of the membranes involved, which is opposite to regular
      intracellular fusion between cytoplasmic leaflets. In addition, our 3D
      reconstructions reveal the presence of clathrin-coated areas at the cytoplasmic
      face of the outer membrane, known to participate in protein sorting to the
      endosomal interior. Interestingly, profiles reminiscent of inward budding
      vesicles were often in close proximity to the coats.

PMID- 14597719
TI  - Nanoshell-mediated near-infrared thermal therapy of tumors under magnetic
      resonance guidance.
AB  - Metal nanoshells are a class of nanoparticles with tunable optical resonances. In
      this article, an application of this technology to thermal ablative therapy for
      cancer is described. By tuning the nanoshells to strongly absorb light in the
      near infrared, where optical transmission through tissue is optimal, a
      distribution of nanoshells at depth in tissue can be used to deliver a
      therapeutic dose of heat by using moderately low exposures of extracorporeally
      applied near-infrared (NIR) light. Human breast carcinoma cells incubated with
      nanoshells in vitro were found to have undergone photothermally induced morbidity
      on exposure to NIR light (820 nm, 35 W/cm2), as determined by using a fluorescent
      viability stain. Cells without nanoshells displayed no loss in viability after
      the same periods and conditions of NIR illumination. Likewise, in vivo studies
      under magnetic resonance guidance revealed that exposure to low doses of NIR
      light (820 nm, 4 W/cm2) in solid tumors treated with metal nanoshells reached
      average maximum temperatures capable of inducing irreversible tissue damage
      (DeltaT = 37.4 +/- 6.6 degrees C) within 4-6 min. Controls treated without
      nanoshells demonstrated significantly lower average temperatures on exposure to
      NIR light (DeltaT < 10 degrees C). These findings demonstrated good correlation
      with histological findings. Tissues heated above the thermal damage threshold
      displayed coagulation, cell shrinkage, and loss of nuclear staining, which are
      indicators of irreversible thermal damage. Control tissues appeared undamaged.

PMID- 14597720
TI  - Disruption of the nonneuronal tph1 gene demonstrates the importance of peripheral
      serotonin in cardiac function.
AB  - Serotonin (5-HT) controls a wide range of biological functions. In the brain, its
      implication as a neurotransmitter and in the control of behavioral traits has
      been largely documented. At the periphery, its modulatory role in physiological
      processes, such as the cardiovascular function, is still poorly understood. The
      rate-limiting enzyme of 5-HT synthesis, tryptophan hydroxylase (TPH), is encoded
      by two genes, the well characterized tph1 gene and a recently identified tph2
      gene. In this article, based on the study of a mutant mouse in which the tph1
      gene has been inactivated by replacement with the beta-galactosidase gene, we
      establish that the neuronal tph2 is expressed in neurons of the raphe nuclei and
      of the myenteric plexus, whereas the nonneuronal tph1, as detected by beta
      galactosidase expression, is in the pineal gland and the enterochromaffin cells.
      Anatomic examination of the mutant mice revealed larger heart sizes than in wild
      type mice. Histological investigation indicates that the primary structure of the
      heart muscle is not affected. Hemodynamic analyses demonstrate abnormal cardiac
      activity, which ultimately leads to heart failure of the mutant animals. This
      report links loss of tph1 gene expression, and thus of peripheral 5-HT, to a
      cardiac dysfunction phenotype. The tph1-/- mutant may be valuable for
      investigating cardiovascular dysfunction observed in heart failure in humans.

PMID- 14597721
TI  - Functional constraints and frequency of deleterious mutations in noncoding DNA of
      rodents.
AB  - Selection against deleterious mutations imposes a mutation load on populations
      because individuals die or fail to reproduce. In vertebrates, estimates of
      genomic rates of deleterious mutations in protein-coding genes imply the
      existence of a substantial mutation load, but many functionally important regions
      of the genome are thought to reside in noncoding DNA, and the contribution of
      noncoding DNA to the mutation load has been unresolved. Here, we infer the
      frequency of deleterious mutations in noncoding DNA of rodents by comparing rates
      of substitution at noncoding nucleotides with rates of substitution at the
      fastest evolving intronic sites of adjacent genes sampled from the whole genome
      sequences of mouse and rat. We show that the major elements of selectively
      constrained noncoding DNA are within 2,500 bp upstream and downstream of coding
      sequences and in first introns. Our estimate of the genomic deleterious point
      mutation rate for noncoding DNA (0.22 per diploid per generation) is similar to
      that for coding DNA. Mammalian populations therefore experience a substantial
      genetic load associated with selection against deleterious mutations in noncoding
      DNA. Deleterious mutations in noncoding DNA have predominantly quantitative
      effects and could be an important source of the burden of complex genetic disease
      variation in human populations.

PMID- 14597722
TI  - Pannexins, a family of gap junction proteins expressed in brain.
AB  - Database search has led to the identification of a family of proteins, the
      pannexins, which share some structural features with the gap junction forming
      proteins of invertebrates and vertebrates. The function of these proteins has
      remained unclear so far. To test the possibility that pannexins underlie
      electrical communication in the brain, we have investigated their tissue
      distribution and functional properties. Here, we show that two of these genes,
      pannexin 1 (Px1) and Px2, are abundantly expressed in the CNS. In many neuronal
      cell populations, including hippocampus, olfactory bulb, cortex and cerebellum,
      there is coexpression of both pannexins, whereas in other brain regions, e.g.,
      white matter, only Px1-positive cells were found. On expression in Xenopus
      oocytes, Px1, but not Px2 forms functional hemichannels. Coinjection of both
      pannexin RNAs results in hemichannels with functional properties that are
      different from those formed by Px1 only. In paired oocytes, Px1, alone and in
      combination with Px2, induces the formation of intercellular channels. The
      functional characteristics of homomeric Px1 versus heteromeric Px1/Px2 channels
      and the different expression patterns of Px1 and Px2 in the brain indicate that
      pannexins form cell type-specific gap junctions with distinct properties that may
      subserve different functions.

PMID- 14597724
TI  - Motility of Escherichia coli cells in clusters formed by chemotactic aggregation.
AB  - Cells of Escherichia coli under conditions of certain cellular stresses excrete
      attractants. Cells of chemotactic strains respond to these excreted signaling
      molecules by moving up their local concentration gradients and forming different
      types of stable multicellular structures. Multicellular clusters are the simplest
      among these structures. Fluorescence microscopy was used to characterize the
      macroscopic properties of the clusters and to track individual E. coli cells in
      the clusters in real time. A quantitative analysis reveals that the equilibrium
      cluster size is only weakly dependent on the total number of cells in the
      cluster. The tumble frequency of an individual cell strongly depends on the
      position of the cell within the cluster and its direction of movement. In the
      central region of the cluster, tumbles are strongly suppressed whereas near the
      edge of the cluster, the tumble frequency is restored for exiting cells, thereby
      preventing them from leaving the cluster, resulting in the maintenance of sharp
      cluster boundaries. A simulation based on a model of the sensory memory of E.
      coli reproduces the experimental data and indicates that the tumble rate and
      consequently the morphology of the cluster are determined by the sensory memory
      of cells.

PMID- 14597723
TI  - Murine cytomegalovirus m157 mutation and variation leads to immune evasion of
      natural killer cells.
AB  - Effective natural killer (NK) cell recognition of murine cytomegalovirus (MCMV)
      infected cells depends on binding of the Ly49H NK cell activation receptor to the
      m157 viral glycoprotein. Here we addressed the immunological consequences of
      variation in m157 sequence and function. We found that most strains of MCMV
      possess forms of m157 that evade Ly49H-dependent NK cell activation. Importantly,
      repeated passage of MCMV through resistant Ly49H+ mice resulted in the rapid
      emergence of m157 mutants that elude Ly49H-dependent NK cell responses. These
      data provide the first molecular evidence that NK cells can exert sufficient
      immunological pressure on a DNA virus, such that it undergoes rapid and specific
      mutation in an NK cell ligand enabling it to evade efficient NK cell
      surveillance.

PMID- 14597725
TI  - Multiple oscillators regulate circadian gene expression in Neurospora.
AB  - High-density microarrays were used to profile circadian gene expression in
      Neurospora crassa cultures grown in constant darkness. We identified 145 clock
      controlled genes (ccgs). The ccgs peaked in mRNA accumulation at all phases of
      the day, with the majority peaking in the late night to early morning. The
      predicted or known functions of the ccgs demonstrate that the clock contributes
      to a wide range of cellular processes, including cell signaling, development,
      metabolism, and stress responses. Although the period of rhythm of most of the
      ccgs was found to depend on the well characterized frequency (FRQ)-based
      oscillator, three ccgs appeared to have a rhythm that was significantly short in
      the long period (29-h) frq7 mutant strain. These ccgs accumulate mRNA
      rhythmically with a circadian period in a frq-null strain, confirming the
      existence of a second oscillator in N. crassa.

PMID- 14597726
TI  - Expression of MRP8 and MRP14 by macrophages is a marker for severe forms of
      glomerulonephritis.
AB  - Expression of two S100 proteins, myeloid related protein (MRP)8 and MRP14, as
      well as their complex formation indicate proinflammatory properties of
      macrophages. We analyzed if the different forms of glomerulonephritis (GN) are
      associated with the appearance of certain phenotypes of infiltrating macrophages
      characterized by expression of MRP8 and MRP14 as well as their complex formation.
      Immunohistochemical analysis of 89 renal biopsies with different forms of
      nephritis revealed that expression and complex formation of MRP8 and MRP14 by
      infiltrating macrophages in the glomeruli correlated with the severity of the
      inflammatory process. As such, MRP8/MRP14-expressing monocytes prevailed in
      highly proliferating forms of GN, i.e., systemic lupus erythematosus GN and
      extracapillary GN. In contrast, a high percentage of macrophages in the renal
      interstitium expressed MRP8 and MRP14 without concomitant formation of their
      complex, and they indicated a chronic type of inflammatory reaction in GN.
      Immunosuppressive drugs had no direct effects on the expression of MRP8 and MRP14
      in macrophages in vitro. The correlation of MRP8 and MRP14 expression with
      disease activity indicates that these calcium-binding proteins are of
      pathophysiological relevance in GN. In addition, our findings reflect differences
      in the inflammatory mechanisms underlying the various forms of GN, as they
      revealed that distinct macrophage subpopulations prevail in the different forms
      of GN.

PMID- 14597727
TI  - Shielding the double-edged sword: negative regulation of the innate immune
      system.
AB  - The innate immune system is evolutionarily conserved among all multicellular
      organisms and is the first line of defense against microorganisms. It enables the
      host not only to combat pathogenic organisms but also to cohabit with
      nonpathogenic microorganisms by balancing the host-microorganism interaction. The
      innate immune response is activated rapidly (within hours) compared with adaptive
      immunity. Activation of the innate immune system allows the activation of the
      adaptive immune response by production of proinflammatory cytokines and by
      providing stimulatory signals via major histocompatibility complex molecules and
      costimulatory molecules such as CD40, CD80, or CD86; together, these lead to the
      full activation of both immune systems to fight against pathogenic
      microorganisms. Activation of the innate immune system, however, can be a double
      edged sword for the host. Proinflammatory cytokines mediate a positive feedback
      loop on the innate immune system, and overproduction of cytokines, if unchecked,
      is hazardous to the host and may cause severe outcomes such as hyperthermia,
      organ failure, and even death in extreme cases. Moreover, if the overproduction
      of proinflammatory cytokines persists, it may cause chronic inflammatory
      diseases. During evolution, the innate immune system has acquired complicated
      regulatory systems to control itself so that this "sword" will not kill the host.
      Various mechanisms including inhibition of Toll-like receptor signaling by
      interleukin-1 receptor-associated kinase-M have evolved for this purpose and are
      important not only to fight against pathogenic microorganisms efficiently but
      also are critical for the peaceful coexistence with commensal bacterial flora.

PMID- 14597728
TI  - Mycobacterial heat shock protein 65 enhances antigen cross-presentation in
      dendritic cells independent of Toll-like receptor 4 signaling.
AB  - Heat shock proteins (HSP) have been shown to enhance antigen processing and
      presentation through their association with antigenic peptides and delivery of
      these moieties into major histocompatibility complex class I pathways. In this
      study, mycobacterial Hsp65 is demonstrated to have the ability to help cross
      present an exogenous protein by dendritic cells (DC) to CD8 T cells without the
      need for complex formation between Hsp65 and the protein. This ability of Hsp65
      to enhance cross-presentation is independent of its weak stimulatory effect on
      DC, the latter seen only after prolonged incubation. When the effect of
      lipopolysaccharide contamination is abrogated, Hsp65 is unable to activate Toll
      like receptor (TLR)4 in the presence of CD14 and MD2. This accounts for the
      inability of Hsp65 to drive maturation of DC and shows that Hsp65 is not a potent
      stimulator of DC. Thus, Hsp65 enhances the cross-presentation of a soluble, free
      antigen by DC, independent of TLR4 signaling and up-regulation of costimulatory
      molecules.

PMID- 14597729
TI  - Trefoil peptide TFF2 treatment reduces VCAM-1 expression and leukocyte
      recruitment in experimental intestinal inflammation.
AB  - There is evidence for a beneficial effect of trefoil peptides in animal models of
      gastric damage and intestinal inflammation, but the optimal treatment strategy
      and the mechanistic basis have not been explored thoroughly. It has been
      suggested that these proteins may modulate the inflammatory response. The aims of
      this study were to compare the protective and curative value of systemic and
      topical trefoil factor family (TFF)2 administration in dextran sulfate sodium
      induced experimental colitis and to investigate the relationship between the
      therapeutic effects of TFF2 and modulation of leukocyte recruitment and
      expression of cell adhesion molecules. Clinical and morphologic severity of
      colitis was evaluated at the end of the study (Day 10). Leukocyte-endothelial
      cell interactions were determined in colonic venules by fluorescence intravital
      microscopy. The expression of cell adhesion molecules vascular cell adhesion
      molecule 1 (VCAM-1) and mucosal addressin cell adhesion molecule 1 (MAdCAM-1) was
      measured by the dual radiolabeled monoclonal antibody technique. Pretreatment
      with TFF2 by subcutaneous or intracolonic (ic) route ameliorated the clinical
      course of colitis, and the luminal route had a significantly superior effect.
      This beneficial effect was correlated with significant reductions in endothelial
      VCAM-1 but not MAdCAM-1 expression and leukocyte adhesion to intestinal venules,
      which returned to levels similar to those of controls. In established colitis, ic
      TFF2 treatment did not modify the severity of colonic lesions. In conclusion,
      TFF2 is useful in the treatment of colitis, and topical administration is
      superior to the systemic route. Reduction in adhesion molecule expression and
      leukocyte recruitment into the inflamed intestine contributes to the beneficial
      effect of this treatment.

PMID- 14597730
TI  - Comparative evaluation of CC chemokine-induced migration of murine CD8alpha+ and
      CD8alpha- dendritic cells and their in vivo trafficking.
AB  - Murine CD11c(+)CD8alpha(-) and CD11c(+)CD8alpha(+) dendritic cells (DCs)
      differentially regulate T cell responses. Although specific chemokines that
      recruit immature (i) or mature (m) CD8alpha(-) DCs have been identified, little
      is known about the influence of chemokines on CD8alpha(+) DCs. iDCs and mDCs
      isolated from spleens of fms-like tyrosine kinase 3 ligand-treated B10 mice were
      compared directly for migratory responses to a panel of CC chemokines or
      following local or systemic administration. In vitro assays were performed using
      Transwell(R) chambers. iDCs did not respond to any CC chemokines tested. Both
      subsets of mDCs migrated to CCL19 and CCL21, with consistently lower percentages
      of CD8alpha(+) DCs migrating. Chemokine receptor mRNA and protein expression were
      analyzed, but no correlation between expression and function was demonstrated. In
      vivo trafficking of fluorochrome-labeled DCs (B10; H2(b)) was assessed by
      immunohistochemistry and by rare-event flow cytometric analysis of allogeneic
      recipient (BALB/c; H2(d)) draining lymph node (DLN) and spleen cells. Twenty-four
      hours after intravenous injection, chloromethylfluorescein diacetate-positive
      CD8alpha(+) and CD8alpha(-) mDCs were detected by immunohistochemistry in spleens
      in similar numbers (that decreased over time). Following subcutaneous injection,
      both DC subsets were detected in DLN at 24 h, but only CD8alpha(-) DCs were
      evident by flow analysis at 48 h. Although CD8alpha(+) DCs migrate from
      peripheral tissues to T cell areas of (allogeneic) secondary lymphoid organs,
      they appear to mobilize as mDCs and less efficiently than CD8alpha(-) mDCs.

PMID- 14597731
TI  - Sulfated sugars for rolling lymphocytes.

PMID- 14597732
TI  - Lymphocyte-HEV interactions in lymph nodes of a sulfotransferase-deficient mouse.
AB  - The interaction of L-selectin expressed on lymphocytes with sulfated sialomucin
      ligands such as CD34 and GlyCAM-1 on high endothelial venules (HEV) of lymph
      nodes results in lymphocyte rolling and is essential for lymphocyte recruitment.
      HEC-GlcNAc6ST-deficient mice lack an HEV-restricted sulfotransferase with
      selectivity for the C-6 position of N-acetylglucosamine (GlcNAc). HEC-GlcNAc6ST-/
      animals exhibit faster lymphocyte rolling and reduced lymphocyte sticking in
      HEV, accounting for the diminished lymphocyte homing. Isolated CD34 and GlyCAM-1
      from HEC-GlcNAc6ST-/- animals incorporate approximately 70% less sulfate than
      ligands from wild-type animals. Furthermore, these ligands exhibit a comparable
      reduction of the epitope recognized by MECA79, a function-blocking antibody that
      reacts with L-selectin ligands in a GlcNAc-6-sulfate-dependent manner. Whereas
      MECA79 dramatically inhibits lymphocyte rolling and homing to lymph nodes in wild
      type mice, it has no effect on HEC-GlcNAc6ST-/- mice. In contrast, in vitro
      rolling on purified GlyCAM-1 from HEC-GlcNAc6ST-/- mice, although greatly
      diminished compared with that on the wild-type ligand, is inhibited by MECA79.
      Our results demonstrate that HEC-GlcNAc6ST contributes predominantly, but not
      exclusively, to the sulfation of HEV ligands for L-selectin and that alternative,
      non-MECA79-reactive ligands are present in the absence of HEC-GlcNAc6ST.

PMID- 14597733
TI  - A novel endothelial L-selectin ligand activity in lymph node medulla that is
      regulated by alpha(1,3)-fucosyltransferase-IV.
AB  - Lymphocytes home to peripheral lymph nodes (PLNs) via high endothelial venules
      (HEVs) in the subcortex and incrementally larger collecting venules in the
      medulla. HEVs express ligands for L-selectin, which mediates lymphocyte rolling.
      L-selectin counterreceptors in HEVs are recognized by mAb MECA-79, a surrogate
      marker for molecularly heterogeneous glycans termed peripheral node addressin. By
      contrast, we find that medullary venules express L-selectin ligands not
      recognized by MECA-79. Both L-selectin ligands must be fucosylated by alpha(1,3)
      fucosyltransferase (FucT)-IV or FucT-VII as rolling is absent in FucT-IV+VII(-/-)
      mice. Intravital microscopy experiments revealed that MECA-79-reactive ligands
      depend primarily on FucT-VII, whereas MECA-79-independent medullary L-selectin
      ligands are regulated by FucT-IV. Expression levels of both enzymes paralleled
      these anatomical distinctions. The relative mRNA level of FucT-IV was higher in
      medullary venules than in HEVs, whereas FucT-VII was most prominent in HEVs and
      weak in medullary venules. Thus, two distinct L-selectin ligands are segmentally
      confined to contiguous microvascular domains in PLNs. Although MECA-79-reactive
      species predominate in HEVs, medullary venules express another ligand that is
      spatially, antigenically, and biosynthetically unique. Physiologic relevance for
      this novel activity in medullary microvessels is suggested by the finding that L
      selectin-dependent T cell homing to PLNs was partly insensitive to MECA-79
      inhibition.

PMID- 14597734
TI  - Down-regulation of CD46 by piliated Neisseria gonorrhoeae.
AB  - Human membrane cofactor protein (CD46) protects host cells against complement
      attack and may function as a receptor for pathogenic Neisseriae. We assessed CD46
      expression in the human cervical cell line ME-180 after exposure to Neisseria
      gonorrhoeae. Piliated but not nonpiliated gonococci adhered to cells and produced
      up to an 80% reduction in CD46 surface expression by 6 h that persisted for at
      least 24 h. This response required a minimum multiplicity of infection of 10 and
      was not prevented by antibodies to CD46. CD46 down-regulation was not
      attributable to intracellular retention or a global or specific shutdown of mRNA
      or protein synthesis. Substantial quantities of CD46 were found in the
      supernatants, indicating a specific shedding of this protein. Adherent gonococci
      lacking the pilus retraction protein PilT did not down-regulate CD46 but de
      repression of pilT expression restored CD46 down-regulation. After experimental
      infection of human volunteers with a gonococcal variant incapable of inducing
      CD46 down-regulation, variants of this strain were reisolated that exhibited CD46
      down-regulation. Pilus-mediated interactions of gonococci with human epithelial
      cells results in a pathogen-induced manipulation of the host cell environment in
      which a membrane protein is removed from epithelial cells by liberation into the
      surrounding milieu.

PMID- 14597735
TI  - L-selectin shedding does not regulate constitutive T cell trafficking but
      controls the migration pathways of antigen-activated T lymphocytes.
AB  - L-selectin mediates rolling of lymphocytes in high endothelial venules (HEVs) of
      peripheral lymph nodes (PLNs). Cross-linking of L-selectin causes proteolytic
      shedding of its ectodomain, the physiological significance of which is unknown.
      To determine whether L-selectin shedding regulates lymphocyte migration, a mutant
      form that resists shedding (LdDeltaP-selectin) was engineered. Transgenic mice
      expressing either LDeltaP or wild-type (WT) L-selectin on T cells were crossed
      with L-selectin knockout (KO) mice. The cellularity and subset composition of
      secondary lymphoid organs did not differ between LDeltaP and WT mice, however,
      they were different from C57BL/6. Plasma levels of soluble L-selectin in LDeltaP
      mice were reduced to <5% of WT and C57BL/6 mice. The rolling properties of T
      lymphocytes from LDeltaP and WT mice on immobilized L-selectin ligands were
      similar. Furthermore, similar numbers of LDeltaP and WT T lymphocytes were
      recruited from the bloodstream into PLNs in mice, although LDeltaP T cells
      transmigrated HEVs more slowly. WT, but not LDeltaP-selectin, underwent rapid,
      metalloproteinase-dependent shedding after TCR engagement, and LDeltaP T cells
      retained the capacity to enter PLNs from the bloodstream. These results suggest
      that the ability to shed L-selectin is not required for T cell recirculation and
      homing to PLNs. However, L-selectin shedding from antigen-activated T cells
      prevents reentry into PLNs.

PMID- 14597736
TI  - Mycobacterium marinum escapes from phagosomes and is propelled by actin-based
      motility.
AB  - Mycobacteria are responsible for a number of human and animal diseases and are
      classical intracellular pathogens, living inside macrophages rather than as free
      living organisms during infection. Numerous intracellular pathogens, including
      Listeria monocytogenes, Shigella flexneri, and Rickettsia rickettsii, exploit the
      host cytoskeleton by using actin-based motility for cell to cell spread during
      infection. Here we show that Mycobacterium marinum, a natural pathogen of fish
      and frogs and an occasional pathogen of humans, is capable of actively inducing
      actin polymerization within macrophages. M. marinum that polymerized actin were
      free in the cytoplasm and propelled by actin-based motility into adjacent cells.
      Immunofluorescence demonstrated the presence of host cytoskeletal proteins,
      including the Arp2/3 complex and vasodilator-stimulated phosphoprotein,
      throughout the actin tails. In contrast, Wiskott-Aldrich syndrome protein
      localized exclusively at the actin-polymerizing pole of M. marinum. These
      findings show that M. marinum can escape into the cytoplasm of infected
      macrophages, where it can recruit host cell cytoskeletal factors to induce actin
      polymerization leading to direct cell to cell spread.

PMID- 14597737
TI  - CCR5 expression influences the progression of human breast cancer in a p53
      dependent manner.
AB  - Chemokines are implicated in tumor pathogenesis, although it is unclear whether
      they affect human cancer progression positively or negatively. We found that
      activation of the chemokine receptor CCR5 regulates p53 transcriptional activity
      in breast cancer cells through pertussis toxin-, JAK2-, and p38 mitogen-activated
      protein kinase-dependent mechanisms. CCR5 blockade significantly enhanced
      proliferation of xenografts from tumor cells bearing wild-type p53, but did not
      affect proliferation of tumor xenografts bearing a p53 mutation. In parallel,
      data obtained in a primary breast cancer clinical series showed that disease-free
      survival was shorter in individuals bearing the CCR5Delta32 allele than in CCR5
      wild-type patients, but only for those whose tumors expressed wild-type p53.
      These findings suggest that CCR5 activity influences human breast cancer
      progression in a p53-dependent manner.

PMID- 14597738
TI  - Regulation of the chemokine receptor CXCR4 by hypoxia.
AB  - Cell adaptation to hypoxia (Hyp) requires activation of transcriptional programs
      that coordinate expression of genes involved in oxygen delivery (via
      angiogenesis) and metabolic adaptation (via glycolysis). Here, we describe that
      oxygen availability is a determinant parameter in the setting of chemotactic
      responsiveness to stromal-derived factor 1 (CXCL12). Low oxygen concentration
      induces high expression of the CXCL12 receptor, CXC receptor 4 (CXCR4), in
      different cell types (monocytes, monocyte-derived macrophages, tumor-associated
      macrophages, endothelial cells, and cancer cells), which is paralleled by
      increased chemotactic responsiveness to its specific ligand. CXCR4 induction by
      Hyp is dependent on both activation of the Hyp-inducible factor 1 alpha and
      transcript stabilization. In a relay multistep navigation process, the Hyp-Hyp
      inducible factor 1 alpha-CXCR4 pathway may regulate trafficking in and out of
      hypoxic tissue microenvironments.

PMID- 14597739
TI  - Age-dependent requirement for gammadelta T cells in the primary but not secondary
      protective immune response against an intestinal parasite.
AB  - Between weaning (3 wk of age) and adulthood (7 wk of age), mice develop increased
      resistance to infection with Eimeria vermiformis, an abundant intestinal parasite
      that causes coccidiosis. This development of resistance was perturbed in T cell
      receptor (TCR)delta(-/-) mice, which at 4 wk of age remained largely susceptible
      to infection and prone to infection-associated dehydration. These phenotypes were
      rescued by the repopulation of gammadelta cells after adoptive transfer of
      lymphoid progenitors into newborn recipients. Because alphabeta T cells are
      necessary and sufficient for the protection of adult mice against E. vermiformis,
      the requirement for gammadelta cells in young mice shows a qualitative difference
      between the cellular immune responses operating at different ages. An important
      contribution toward primary immune protection in young hosts may have provided a
      strong selective pressure for the evolutionary conservation of gammadelta cells.
      This notwithstanding, the development of effective, pathogen-specific immunity in
      young mice requires alphabeta T cells, just as it does in adult mice.

PMID- 14597740
TI  - The cellular location of self-antigen determines the positive and negative
      selection of autoreactive B cells.
AB  - Systemic autoimmune disease is frequently characterized by the production of
      autoantibodies against widely expressed intracellular self-antigens, whereas B
      cell tolerance to ubiquitous and highly expressed extracellular antigens is
      strictly enforced. To test for differences in the B cell response to
      intracellular and extracellular self-antigens, we sequestered a tolerogenic cell
      surface antigen intracellularly by addition of a two amino acid endoplasmic
      reticulum (ER) retention signal. In contrast to cell surface antigen, which
      causes the deletion of autoreactive B cells, the intracellularly sequestered self
      antigen failed to induce B cell tolerance and was instead autoimmunogenic. The
      intracellular antigen positively selected antigen-binding B cells to
      differentiate into B1 cells and induced large numbers of IgM autoantibody
      secreting plasma cells in a T-independent manner. By analyzing the impact of
      differences in subcellular distribution independently from other variables, such
      as B cell receptor affinity, antigen type, or tissue distribution, we have
      established that intracellular localization of autoantigen predisposes for
      autoantibody production. These findings help explain why intracellular antigens
      are targeted in systemic autoimmune diseases.

PMID- 14597741
TI  - High-dose methotrexate-based chemotherapy followed by consolidating radiotherapy
      in non-AIDS-related primary central nervous system lymphoma: European
      Organization for Research and Treatment of Cancer Lymphoma Group Phase II Trial
      20962.
AB  - PURPOSE: To confirm the feasibility and estimate the efficacy of methotrexate
      (MTX), teniposide, carmustine, and methylprednisolone (MBVP) chemotherapy
      combined with radiotherapy (RT) for patients with non-AIDS-related primary CNS
      lymphoma (PCNSL) treated in a multicenter setting. PATIENTS AND METHODS:
      Treatment consisted of two cycles of MBVP (MTX 3 g/m2 days 1 and 15, teniposide
      100 mg/m2 days 2 and 3, carmustine 100 mg/m2 day 4, methylprednisolone 60 mg/m2
      days 1 to 5, and two intrathecal injections of MTX 15 mg, cytarabine 40 mg, and
      hydrocortisone 25 mg) followed by 40 Gy of RT. Primary end points were response
      and safety of this regimen. RESULTS: Twelve centers included 52 patients who were
      all analyzed on an intent-to-treat basis. Median follow-up of all patients was 27
      months. One patient progressed and died before treatment, and five patients died
      during treatment. Four patients received RT after one cycle of chemotherapy, and
      42 patients completed the entire treatment. Hematologic grade 3 and 4 toxicity
      was seen in 78% of patients for leukocytes and 24% of patients for platelets. The
      overall response rate of all 52 patients was 81%. Two patients who did not
      fulfill the criteria of objective response survived more than 1 year; one of them
      is still alive without disease. Eighteen patients died; 11 deaths were a result
      of tumor, five were probably treatment-related, one was caused by late
      leukoencephalopathy, and one was a result of intercurrent disease. Median
      estimated overall survival was 46 months. CONCLUSION: MBVP followed by RT for
      PCNSL has a high response rate. However, the 10% toxic death rate during
      treatment in a multicenter setting underlines the need for highly specialized
      care.

PMID- 14597742
TI  - An attenuated adenovirus, ONYX-015, as mouthwash therapy for premalignant oral
      dysplasia.
AB  - PURPOSE: Dysplastic lesions of the oral epithelium are known precursors of oral
      cancer. A significant proportion of oral dysplastic lesions have functional
      defects in p53 response pathways. The ONYX-015 adenovirus is selectively
      cytotoxic to cells carrying defects in p53-dependent signaling pathways. The
      current study sought to establish the feasibility and activity of ONYX-015
      administered topically as a mouthwash to patients with clinically apparent and
      histologically dysplastic lesions of the oral mucosa. PATIENTS AND METHODS: A
      total of 22 patients (19 assessable patients) were enrolled onto the study. ONYX
      015 was administered on three different schedules to consecutive cohorts.
      Biopsies of the involved mucosa were performed to evaluate histologic response
      and changes in expression of putative markers of malignant potential, including
      p53, cyclin D1, and Ki-67. Serology was performed to measure antiadenoviral
      titers. RESULTS: Histologic resolution of dysplasia was seen in seven (37%) of 19
      patients, and the grade of dysplasia improved in one additional patient. The
      majority of responses were transient. No toxicity greater than grade 2 (febrile
      episode in one patient) was observed. Only one of seven patients demonstrated an
      increase in circulating antiadenoviral antibody titer while on therapy. Although
      responding and resistant lesions had similar mean p53 staining at baseline,
      histologic response correlated with a decrease in p53 positivity over time.
      Significant changes in cyclin D1 or Ki-67 were not observed. Viral replication
      was confirmed in two of three lesions examined. CONCLUSION: This novel approach
      to cancer prevention is tolerable, feasible, and has demonstrable activity.

PMID- 14597743
TI  - Radiotherapy patterns of care study in lung carcinoma.
AB  - PURPOSE: For the first time, a lung Patterns of Care Study was conducted to
      determine the national patterns of radiation (RT) practice in patients treated
      for nonmetastatic lung cancer in 1998 to 1999. MATERIALS AND METHODS: A national
      survey of randomly selected RT institutions in the United States was conducted
      using two-stage cluster sampling, stratified by practice type. Patients with
      nonmetastatic lung cancer (Karnofsky performance score [KPS] > or = 60), who
      received RT as definitive or adjuvant therapy, were randomly selected. To
      determine national estimates, sample size was weighted by the relative number of
      institutions per strata and the number of patient records reviewed per the number
      of patients eligible. Accordingly, 42,335 patient records from 58 institutions
      were reviewed by trained research associates. The unweighted sample size (or
      number of patients) was 541. RESULTS: The histologies were small-cell lung cancer
      (SCLC) in 14.5% of patients versus non-small-cell lung cancer (NSCLC) in 85.5% of
      patients. The median age was 67 years (range, 29 to 92 years); 61% of patients
      were male, and 38% were current smokers. Bone scans and brain imaging were not
      obtained in 34% and 52% of clinical stage (CS) III NSCLC patients, respectively.
      Regarding treatment strategies, for SCLC and CS III NSCLC, chemotherapy plus RT
      was used significantly more than RT alone (P <.05); in CS I NSCLC, RT alone was
      the primary treatment (P <.05). Overall, 58% of patients received systemic
      therapy. On multivariate analysis, factors correlating with increased use of
      chemotherapy included younger age, histology (SCLC > NSCLC), increasing CS,
      increasing KPS, and lack of comorbidities. Only 3% of all patients were treated
      on prospective clinical trials. CONCLUSION: This study establishes the general
      patterns of care for lung carcinoma in RT facilities within the United States. As
      supported by clinical trials, patients with limited-stage SCLC and CS III NSCLC
      received chemotherapy plus RT more than they received RT alone. Further
      improvements in staging, smoking cessation, and increased accrual to clinical
      trials must be encouraged.

PMID- 14597744
TI  - Primary central nervous system lymphoma: results of a pilot and phase II study of
      systemic and intraventricular chemotherapy with deferred radiotherapy.
AB  - PURPOSE: To evaluate response rate, response duration, overall survival (OS), and
      toxicity in primary CNS lymphoma (PCNSL) after systemic and intraventricular
      chemotherapy with deferred radiotherapy. PATIENTS AND METHODS: From September
      1995 to July 2001, 65 consecutive patients with PCNSL (median age, 62 years) were
      enrolled onto a pilot and phase II study evaluating chemotherapy without
      radiotherapy. A high-dose methotrexate (MTX; cycles 1, 2, 4, and 5) and
      cytarabine (ARA-C; cycles 3 and 6)-based systemic therapy (including
      dexamethasone, vinca-alkaloids, ifosfamide, and cyclophosphamide) was combined
      with intraventricular MTX, prednisolone, and ARA-C. RESULTS: Sixty-one of 65
      patients were assessable for response. Of these, 37 patients (61%) achieved
      complete response, six (10%) achieved partial response, and 12 (19%) progressed
      under therapy. Six (9%) of 65 patients died because of treatment-related
      complications. Follow-up is 0 to 87 months (median, 26 months). The Kaplan-Meier
      estimates for median time to treatment failure (TTF) and median OS were 21 months
      and 50 months, respectively. For patients older than 60 years, median survival
      was 34 months, and the median TTF was 15 months. In patients younger than 61
      years, median survival and median TTF have not been reached yet; the 5-year
      survival fraction is 75%. Systemic toxicity was mainly hematologic. Ommaya
      reservoir infection occurred in 12 patients (19%), and permanent cognitive
      dysfunction possibly as a result of treatment occurred in only two patients (3%).
      CONCLUSION: Primary chemotherapy based on high-dose MTX and ARA-C is highly
      efficient in PCNSL. Response rate and response duration in this series are
      comparable to the response rates and durations reported after combined
      radiotherapy and chemotherapy. Neurotoxicity was infrequent.

PMID- 14597745
TI  - Primary central nervous system lymphoma: a curable brain tumor.

PMID- 14597746
TI  - Topical ONYX-015 in the treatment of premalignant oral dysplasia: another role
      for the cold virus?

PMID- 14597747
TI  - Patterns of care studies: creating "an environment of watchful concern".

PMID- 14597749
TI  - The WTO's balancing act.
AB  - The 146 member nations of the World Trade Organization recently came to an
      agreement that will allow poor nations to avoid patent restrictions and import
      generic versions of urgently needed medicines, but this accord has been met with
      criticism from international aid organizations. What effects will this agreement
      have on reducing the burden of disease in the developing world, and also on the
      pharmaceutical industry?

PMID- 14597750
TI  - Genetic counselors: translating genomic science into clinical practice.
AB  - In a time of emerging genetic tests and technologies, genetic counselors are
      faced with the challenge of translating complex genomic data into information
      that will aid their client's ability to learn about, understand, make, and cope
      with decisions relating to genetic diagnoses. The first of two companion articles
      in this issue examines the role of the genetic counselor, particularly in
      counseling individuals at risk for or diagnosed with breast cancer, in an era of
      high-tech health care and gene patents.

PMID- 14597751
TI  - Genetic counseling throughout the life cycle.
AB  - As the definition of genetic counseling continues to evolve, so does the
      application of genetic counseling services in all areas of medicine and
      throughout the human life cycle. While governmental policy, economics, ethics,
      and religion continue to influence society's views regarding the necessity of
      testing germ cells for mutations to prevent the birth of an affected child or
      predicting whether healthy adults will develop future life-threatening illness,
      patient autonomy in the choice of whether to know, or not know, one's genetic
      make-up remains a core principle of genetic counseling.

PMID- 14597752
TI  - Bacterial communication and group behavior.
AB  - The existence of species-specific and interspecies bacterial cell-cell
      communication and group organization was only recently accepted. Researchers are
      now realizing that the ability of these microbial teams to communicate and form
      structures, known as biofilms, at key times during the establishment of infection
      significantly increases their ability to evade both host defenses and
      antibiotics. This Perspective series discusses the known signaling mechanisms,
      the roles they play in both chronic Gram-positive and Gram-negative infections,
      and promising therapeutic avenues of investigation.

PMID- 14597753
TI  - Interspecies communication in bacteria.
AB  - Until recently, bacteria were considered to live rather asocial, reclusive lives.
      New research shows that, in fact, bacteria have elaborate chemical signaling
      systems that enable them to communicate within and between species. One signal,
      termed AI-2, appears to be universal and facilitates interspecies communication.
      Many processes, including virulence factor production, biofilm formation, and
      motility, are controlled by AI-2. Strategies that interfere with communication in
      bacteria are being explored in the biotechnology industry with the aim of
      developing novel antimicrobials. AI-2 is a particularly attractive candidate for
      such studies because of its widespread use in the microbial kingdom.

PMID- 14597754
TI  - Pharmacological inhibition of quorum sensing for the treatment of chronic
      bacterial infections.
AB  - Traditional treatment of infectious diseases is based on compounds that aim to
      kill or inhibit bacterial growth. A major concern with this approach is the
      frequently observed development of resistance to antimicrobial compounds. The
      discovery of bacterial-communication systems (quorum-sensing systems), which
      orchestrate important temporal events during the infection process, has afforded
      a novel opportunity to ameliorate bacterial infection by means other than growth
      inhibition. Compounds able to override bacterial signaling are present in nature.
      Herein we discuss the known signaling mechanisms and potential antipathogenic
      drugs that specifically target quorum-sensing systems in a manner unlikely to
      pose a selective pressure for the development of resistant mutants.

PMID- 14597755
TI  - Decreased elastin in vessel walls puts the pressure on.
AB  - Mice haploinsufficient for elastin develop structural changes in vessel walls
      similar to those seen in patients with mutations in the elastin gene. A new study
      demonstrates that due to mechanical changes in the vessel wall, these animals
      exhibit increased mean arterial pressures. The results evoke the possibility that
      alterations in elastin may contribute to the development of essential
      hypertension in patients.

PMID- 14597756
TI  - The origin of FOXP3-expressing CD4+ regulatory T cells: thymus or periphery.
AB  - Naturally arising CD4+ regulatory T cells, which engage in the maintenance of
      immunologic self-tolerance, specifically express FOXP3, which encodes a
      transcription-repressor protein. Genetic defects in FOXP3 cause IPEX, an X-linked
      autoimmune/inflammatory syndrome. With FOXP3 as a specific marker for regulatory
      CD4+ T cells in humans, it is now possible to determine their origin and
      developmental pathway.

PMID- 14597757
TI  - Tales from the crypt.
AB  - Intestinal colonic crypts are derived from a stem cell population located at the
      base of each crypt. A new analysis of mitochondrial function and of the rates of
      mitochondrial DNA (mtDNA) mutation in individual crypts shows that mtDNA
      mutations arise in stem cells - and at a surprisingly high frequency. Because
      crypts turn over extremely rapidly (about once per week), somatic mtDNA mutations
      can "take over the system" and even become homoplasmic, in a manner similar to
      what has been shown to occur in tumors.

PMID- 14597758
TI  - The TRAIL to arthritis.
AB  - Antigen-specific lymphocytes are involved in synovial proliferation within
      inflamed joints. Activated lymphocytes and synoviocytes from patients with
      rheumatoid arthritis express receptors that can bind TNF-related apoptosis
      inducing ligand (TRAIL). A new study demonstrates that DCs pulsed with collagen
      and transduced with an adenovirus-based vector able to express TRAIL limit the
      incidence of arthritis in a model of collagen-induced arthritis and joint
      inflammation. These results suggest that gene-modified cell therapy represents a
      therapeutic option for systemic rheumatic diseases.

PMID- 14597759
TI  - Angiotensin II-accelerated atherosclerosis and aneurysm formation is attenuated
      in osteopontin-deficient mice.
AB  - Osteopontin (OPN) is expressed in atherosclerotic lesions, particularly in
      diabetic patients. To determine the role of OPN in atherogenesis, ApoE-/-OPN+/+,
      ApoE-/-OPN+/-, and ApoE-/-OPN-/- mice were infused with Ang II, inducing vascular
      OPN expression and accelerating atherosclerosis. Compared with ApoE-/-OPN+/+
      mice, ApoE-/-OPN+/- and ApoE-/-OPN-/- mice developed less Ang II-accelerated
      atherosclerosis. ApoE-/- mice transplanted with bone marrow derived from ApoE-/
      OPN-/- mice had less Ang II-induced atherosclerosis compared with animals
      receiving ApoE-/-OPN+/+ cells. Aortae from Ang II-infused ApoE-/-OPN-/- mice
      expressed less CD68, C-C-chemokine receptor 2, and VCAM-1. In response to
      intraperitoneal thioglycollate, recruitment of leukocytes in OPN-/- mice was
      impaired, and OPN-/- leukocytes exhibited decreased basal and MCP-1-directed
      migration. Furthermore, macrophage viability in atherosclerotic lesions from Ang
      II-infused ApoE-/-OPN-/- mice was decreased. Finally, Ang II-induced abdominal
      aortic aneurysm formation in ApoE-/-OPN-/- mice was reduced and associated with
      decreased MMP-2 and MMP-9 activity. These data suggest an important role for
      leukocyte-derived OPN in mediating Ang II-accelerated atherosclerosis and
      aneurysm formation.

PMID- 14597761
TI  - Mitochondrial DNA mutations in human colonic crypt stem cells.
AB  - The mitochondrial genome encodes 13 essential subunits of the respiratory chain
      and has remarkable genetics based on uniparental inheritance. Within human
      populations, the mitochondrial genome has a high rate of sequence divergence with
      multiple polymorphic variants and thus has played a major role in examining the
      evolutionary history of our species. In recent years it has also become apparent
      that pathogenic mitochondrial DNA (mtDNA) mutations play an important role in
      neurological and other diseases. Patients harbor many different mtDNA mutations,
      some of which are mtDNA mutations, some of which are inherited, but others that
      seem to be sporadic. It has also been suggested that mtDNA mutations play a role
      in aging and cancer, but the evidence for a causative role in these conditions is
      less clear. The accumulated data would suggest, however, that mtDNA mutations
      occur on a frequent basis. In this article we describe a new phenomenon: the
      accumulation of mtDNA mutations in human colonic crypt stem cells that result in
      a significant biochemical defect in their progeny. These studies have important
      consequences not only for understanding of the finding of mtDNA mutations in
      aging tissues and tumors, but also for determining the frequency of mtDNA
      mutations within a cell.

PMID- 14597760
TI  - CII-DC-AdTRAIL cell gene therapy inhibits infiltration of CII-reactive T cells
      and CII-induced arthritis.
AB  - Previously, we described an APC-adenovirus (APC-Ad) FasL cell gene therapy method
      which could be used to deplete autoreactive T cells in vivo. FasL was toxic,
      however, and controlled regulation of FasL was not achieved. Here we describe an
      improved approach to delivering TNF-related apoptosis-inducing ligand (TRAIL) in
      vivo in which collagen II-induced (CII-induced) arthritis-susceptible (CIA
      susceptible) DBA/1j mice were treated with CII-pulsed DCs that had been
      transfected with a novel Ad system. The Ad was engineered to exhibit inducible
      TRAIL under the control of the doxycycline-inducible (DOX-inducible) tetracycline
      response element (TRE). Four groups of mice were treated with CII-DC-AdTRAIL+DOX,
      CII-DC-AdTRAIL (no DOX), CII-DC-AdGFP+DOX, or DC-AdTRAIL+DOX (no CII), beginning
      2 weeks after priming with CII in CFA. The incidence of arthritis and
      infiltration of T cells in the joint was significantly decreased in CII-DC
      AdTRAIL+DOX-treated mice. The in vitro splenic T cell proliferative response and
      induction of IFN-gamma to bovine CII stimulation were also significantly reduced
      in mice treated with CII-DC-AdTRAIL+DOX. AdTRAIL+DOX was not toxic to DCs or mice
      but could induce activated T cells to undergo apoptosis in the spleen. Our
      results suggest that CII-DC-AdTRAIL+DOX cell gene therapy is a safe and effective
      method for inhibiting the development of CIA.

PMID- 14597762
TI  - Activation of diverse repertoires of autoreactive T cells enhances the loss of
      anti-dsDNA B cell tolerance.
AB  - CD4+ helper T cells play a critical role in the production of the antinuclear
      autoantibodies that characterize systemic lupus erythematosus in mice and humans.
      A key issue is whether this help is derived from a diverse repertoire of
      autoreactive CD4+ T cells or from a select number of T cells of limited
      specificity. We used the chronic graft-versus-host disease model to define the
      diversity of the CD4+ T cell repertoire required to induce the autoantibody
      response. By transferring clonally restricted versus clonally diverse populations
      of MHC class II-reactive CD4+ T cells, we show that the loss of B cell tolerance
      to nuclear antigens has two distinct components with different CD4+ cell
      requirements. Activation of limited repertoires of CD4+ T cells was sufficient
      for the expansion of anergized anti-double-stranded DNA B cells and production of
      IgM autoantibodies. Unexpectedly, we found that CD4+ T cell diversity was
      necessary for CD4+ T cell trafficking into the follicle and for the generation of
      isotype-switched IgG autoantibodies. Importantly, combining two limited
      repertoires of T cells provides sufficient CD4+ T cell diversity to drive
      antinuclear Ab production. These data demonstrate that a diverse CD4+ T cell
      repertoire is required to generate a sustained effector B cell response capable
      of mediating systemic autoimmunity.

PMID- 14597763
TI  - Alteration of the 4-sphingenine scaffolds of ceramides in keratinocyte-specific
      Arnt-deficient mice affects skin barrier function.
AB  - Aryl hydrocarbon receptor nuclear translocator (ARNT), a transcription factor of
      the Per/AHR/ARNT/Sim family, regulates gene expression in response to
      environmental stimuli including xenobiotics and hypoxia. To examine its role in
      the epidermis, the Cre-loxP system was used to disrupt the Arnt gene in a
      keratinocyte-specific manner. Gene-targeted, newborn mice with almost normal
      appearance died neonatally of severe dehydration caused by water loss. Histology
      showed small changes in the architecture of cornified layers, with apparently
      preserved intercorneocyte lamellar structures responsible for the skin barrier
      function. In contrast, HPLC/ion-trap mass spectrometry revealed significant
      alterations in the compositions of ceramides, the major components of the
      lamellae. The murine epidermal ceramides normally contain 4-sphingenine and 4
      hydroxysphinganine. In Arnt-null epidermis, 4-sphingenine was largely replaced by
      sphinganine and the amounts of ceramides with 4-hydroxysphinganine were greatly
      decreased, suggesting deficiency of dihydroceramide desaturases that catalyze the
      formation of both 4-sphingenyl and 4-hydroxysphinganyl moieties. A desaturase
      isoenzyme, DES-1, prefers desaturation, but DES-2 catalyzes both reactions to a
      similar extent. Transcript levels of Des-2, but not Des-1, were considerably
      decreased in cultured keratinocytes from Arnt-null epidermis. These results
      indicate that proper ceramide compositions through 4-desaturation regulated by
      ARNT are crucial for maintaining the epidermal barrier function.

PMID- 14597764
TI  - NADPH oxidase signal transduces angiotensin II in hepatic stellate cells and is
      critical in hepatic fibrosis.
AB  - Angiotensin II (Ang II) is a pro-oxidant and fibrogenic cytokine. We investigated
      the role of NADPH oxidase in Ang II-induced effects in hepatic stellate cells
      (HSCs), a fibrogenic cell type. Human HSCs express mRNAs of key components of
      nonphagocytic NADPH oxidase. Ang II phosphorylated p47phox, a regulatory subunit
      of NADPH oxidase, and induced reactive oxygen species formation via NADPH oxidase
      activity. Ang II phosphorylated AKT and MAPKs and increased AP-1 DNA binding in a
      redox-sensitive manner. Ang II stimulated DNA synthesis, cell migration,
      procollagen alpha1(I) mRNA expression, and secretion of TGF-beta1 and
      inflammatory cytokines. These effects were attenuated by N-acetylcysteine and
      diphenylene iodonium, an NADPH oxidase inhibitor. Moreover, Ang II induced
      upregulation of genes potentially involved in hepatic wound-healing response in a
      redox-sensitive manner, as assessed by microarray analysis. HSCs isolated from
      p47phox-/- mice displayed a blunted response to Ang II compared with WT cells. We
      also assessed the role of NADPH oxidase in experimental liver fibrosis. After
      bile duct ligation, p47phox-/- mice showed attenuated liver injury and fibrosis
      compared with WT counterparts. Moreover, expression of smooth muscle alpha-actin
      and expression of TGF-beta1 were reduced in p47phox-/- mice. Thus, NADPH oxidase
      mediates the actions of Ang II on HSCs and plays a critical role in liver
      fibrogenesis.

PMID- 14597766
TI  - Stem cell factor restores hepatocyte proliferation in IL-6 knockout mice
      following 70% hepatectomy.
AB  - Stem cell factor (SCF) is a molecule with known proliferative effects on
      hematopoietic cells. More recent studies suggest that this molecule may also have
      effects on cellular differentiation and proliferation in other types of cells.
      The current investigations demonstrate that there is a large reservoir of SCF in
      the liver, that hepatic SCF levels change dramatically following partial
      hepatectomy in mice, and that SCF blockade, either by administration of anti-SCF
      antibodies or by using genetically altered, SCF-deficient mice, inhibits
      hepatocyte proliferation after partial hepatectomy; if SCF is replaced in the
      genetically SCF-deficient mice after partial hepatectomy, hepatocyte
      proliferation is restored to that seen in WT animals. Furthermore, SCF
      administration to IL-6 knockout mice also restores hepatocyte proliferation to
      normal. In vitro studies using primary mouse hepatocytes demonstrate that SCF
      causes hepatocyte proliferation and is induced by IL-6 and that treatment with
      anti-SCF antibodies inhibits IL-6-induced hepatocyte proliferation. Further in
      vivo studies in IL-6 knockout mice demonstrate that SCF administration to these
      animals increases p-stat3 levels, suggesting that the SCF-induced increase in
      hepatocyte proliferation in this system is stat3-mediated.

PMID- 14597765
TI  - Inhibition of endogenous thioredoxin in the heart increases oxidative stress and
      cardiac hypertrophy.
AB  - Thioredoxin 1 (Trx1) has redox-sensitive cysteine residues and acts as an
      antioxidant in cells. However, the extent of Trx1 contribution to overall
      antioxidant mechanisms is unknown in any organs. We generated transgenic mice
      with cardiac-specific overexpression of a dominant negative (DN) mutant
      (C32S/C35S) of Trx1 (Tg-DN-Trx1 mice), in which the activity of endogenous Trx
      was diminished. Markers of oxidative stress were significantly increased in
      hearts from Tg-DN-Trx1 mice compared with those from nontransgenic (NTg) mice. Tg
      DN-Trx1 mice exhibited cardiac hypertrophy with maintained cardiac function at
      baseline. Intraperitoneal injection of N-2-mercaptopropionyl glycine, an
      antioxidant, normalized cardiac hypertrophy in Tg-DN-Trx1 mice. Thoracic aortic
      banding caused greater increases in myocardial oxidative stress and enhanced
      hypertrophy in Tg-DN-Trx1 compared with NTg mice. In contrast, transgenic mice
      with cardiac-specific overexpression of wild-type Trx1 did not show cardiac
      hypertrophy at baseline but exhibited reduced levels of hypertrophy and oxidative
      stress in response to pressure overload. These results demonstrate that
      endogenous Trx1 is an essential component of the cellular antioxidant mechanisms
      and plays a critical role in regulating oxidative stress in the heart in vivo.
      Furthermore, inhibition of endogenous Trx1 in the heart primarily stimulates
      hypertrophy, both under basal conditions and in response to pressure overload
      through redox-sensitive mechanisms.

PMID- 14597767
TI  - Developmental adaptation of the mouse cardiovascular system to elastin
      haploinsufficiency.
AB  - Supravalvular aortic stenosis is an autosomal-dominant disease of elastin (Eln)
      insufficiency caused by loss-of-function mutations or gene deletion. Recently, we
      have modeled this disease in mice (Eln+/-) and found that Eln haploinsufficiency
      results in unexpected changes in cardiovascular hemodynamics and arterial wall
      structure. Eln+/- animals were found to be stably hypertensive from birth, with a
      mean arterial pressure 25-30 mmHg higher than their wild-type counterparts. The
      animals have only moderate cardiac hypertrophy and live a normal life span with
      no overt signs of degenerative vascular disease. Examination of arterial
      mechanical properties showed that the inner diameters of Eln+/- arteries were
      generally smaller than wild-type arteries at any given intravascular pressure.
      Because the Eln+/- mouse is hypertensive, however, the effective arterial working
      diameter is comparable to that of the normotensive wild-type animal.
      Physiological studies indicate a role for the renin-angiotensin system in
      maintaining the hypertensive state. The association of hypertension with elastin
      haploinsufficiency in humans and mice strongly suggests that elastin and other
      proteins of the elastic fiber should be considered as causal genes for essential
      hypertension.

PMID- 14597769
TI  - Induction of FoxP3 and acquisition of T regulatory activity by stimulated human
      CD4+CD25- T cells.
AB  - CD4+CD25+ regulatory T (TR) cells have been described in both humans and mice. In
      mice, TR are thymically derived, and lack of TR leads to organ-specific
      autoimmunity. Recently, the forkhead/winged helix transcription factor, FoxP3,
      has been shown to be important for the function of TR cells in mice. In this
      study, human TR cells were examined and, in results similar to those of studies
      done in mice, expression of FoxP3 was found exclusively in CD4+CD25+ T cells and
      correlated with the suppressive activity of these cells. In contrast to the mouse
      studies, activation of human CD4+CD25- T cells led to expression of FoxP3.
      Expression of FoxP3 in activated human CD4+CD25+ cells also correlated with
      suppression of proliferation by these cells in freshly isolated CD4+CD25- T cells
      from the same donor. This suppression was cell-contact dependent and cytokine
      independent. Thus, in humans, during activation of CD4+CD25- T cells in an immune
      response, two populations of cells may arise, effector CD4+CD25+ and regulatory
      CD4+CD25+ T cells, with expression of FoxP3 correlated with regulatory activity.
      These data also raise the possibility that a failure to generate peripheral TR
      cells properly may contribute to autoimmune disease and suggest a possible
      therapeutic role for FoxP3 in the treatment of such diseases.

PMID- 14597768
TI  - Mammary-specific deletion of parathyroid hormone-related protein preserves bone
      mass during lactation.
AB  - Large amounts of calcium are transferred to offspring by milk. This demand
      results in negative calcium balance in lactating mothers and is associated with
      rapid bone loss. The mechanisms of bone loss during lactation are only partly
      understood. Several studies have suggested that parathyroid hormone-related
      protein (PTHrP) might be secreted into the circulation by the lactating mammary
      gland and regulate bone turnover during lactation. Because mammary development
      fails in the absence of PTHrP, conventional PTHrP knockout mice cannot be used to
      address this possibility. To examine this hypothesis, we therefore used mice
      carrying a beta-lactoglobulin promoter-driven Cre transgene, one null PTHrP
      allele, and one floxed PTHrP allele. Expression of Cre specifically in mammary
      epithelial cells during late pregnancy and lactation resulted in efficient
      deletion of the PTHrP gene; mammary gland PTHrP mRNA and milk PTHrP protein were
      almost completely absent. Removal of PTHrP from the lactating mammary glands
      resulted in reductions in levels of circulating PTHrP and 1,25-dihydroxy vitamin
      D and urinary cAMP. In addition, bone turnover was reduced and bone loss during
      lactation was attenuated. We conclude that during lactation mammary epithelial
      cells are a source of circulating PTHrP that promotes bone loss by increasing
      rates of bone resorption.

PMID- 14597770
TI  - Expression of the alpha1beta1 integrin, VLA-1, marks a distinct subset of human
      CD4+ memory T cells.
AB  - The alpha1beta1 integrin, very late antigen-1 (VLA-1), is a collagen receptor
      expressed in many CD4+ T cells localizing to inflamed tissues. Here we show that
      the expression of VLA-1 is a stable marker of a distinct subset of CD4+ memory T
      cells. Thus, in human peripheral blood lymphocytes (PBLs), approximately 1-4% of
      the CD4+ T cells express VLA-1, and following T cell receptor activation ex vivo,
      the percentage of VLA-1+ cells increases within the CD45RO+ population.
      Importantly, the activated VLA-1+ and VLA-1- cells can be isolated and maintained
      in culture as phenotypically stable subsets. Functionally, CD4+ memory T cells,
      operationally defined as the cells that divide rapidly following stimulation with
      a recall antigen, are highly enriched for VLA-1+ cells. Moreover, depletion of
      the small fraction of VLA-1+ cells present in CD4+ PBLs prior to stimulation
      significantly abrogated the proliferative response to recall antigens. Notably,
      the VLA-1+ cells in fresh CD4+ PBLs are composed of resting CD45RO+/RA-, CCR7-,
      CD62L+, CD25-, and VLA-4hi cells. Interestingly, this VLA-1+ subset is enriched
      for Th1-type cells, and Th1-polarizing conditions during T cell activation favor
      the emergence of VLA-1+ cells. Thus, VLA-1 expression is a stable marker of a
      unique subset of human memory CD4+ T cells that predominantly differentiates into
      Th1 cells.

PMID- 14597771
TI  - Proteolytic release of the carboxy-terminal fragment of proHB-EGF causes nuclear
      export of PLZF.
AB  - Cleavage of membrane-anchored heparin-binding EGF-like growth factor (proHB-EGF)
      via metalloprotease activation yields amino- and carboxy-terminal regions (HB-EGF
      and HB-EGF-C, respectively), with HB-EGF widely recognized as a key element of
      epidermal growth factor receptor transactivation in G protein-coupled receptor
      signaling. Here, we show a biological role of HB-EGF-C in cells. Subsequent to
      proteolytic cleavage of proHB-EGF, HB-EGF-C translocated from the plasma membrane
      into the nucleus. This translocation triggered nuclear export of the
      transcriptional repressor, promyelocytic leukemia zinc finger (PLZF), which we
      identify as an HB-EGF-C binding protein. Suppression of cyclin A and delayed
      entry of S-phase in cells expressing PLZF were reversed by the production of HB
      EGF-C. These results indicate that released HB-EGF-C functions as an
      intracellular signal and coordinates cell cycle progression with HB-EGF.

PMID- 14597772
TI  - Avidity enhancement of L-selectin bonds by flow: shear-promoted rotation of
      leukocytes turn labile bonds into functional tethers.
AB  - L-selectin is a key lectin essential for leukocyte capture and rolling on vessel
      walls. Functional adhesion of L-selectin requires a minimal threshold of
      hydrodynamic shear. Using high temporal resolution videomicroscopy, we now report
      that L-selectin engages its ligands through exceptionally labile adhesive bonds
      (tethers) even below this shear threshold. These tethers share a lifetime of 4 ms
      on distinct physiological ligands, two orders of magnitude shorter than the
      lifetime of the P-selectin-PSGL-1 bond. Below threshold shear, tether duration is
      not shortened by elevated shear stresses. However, above the shear threshold,
      selectin tethers undergo 14-fold stabilization by shear-driven leukocyte
      transport. Notably, the cytoplasmic tail of L-selectin contributes to this
      stabilization only above the shear threshold. These properties are not shared by
      P-selectin- or VLA-4-mediated tethers. L-selectin tethers appear adapted to
      undergo rapid avidity enhancement by cellular transport, a specialized mechanism
      not used by any other known adhesion receptor.

PMID- 14597774
TI  - SUMO-2/3 regulates topoisomerase II in mitosis.
AB  - We have analyzed the abundance of SUMO-conjugated species during the cell cycle
      in Xenopus egg extracts. The predominant SUMO conjugation products associated
      with mitotic chromosomes arose from SUMO conjugation of topoisomerase II.
      Topoisomerase II was modified exclusively by SUMO-2/3 during mitosis under normal
      circumstances, although we observed conjugation of topoisomerase II to SUMO-1 in
      extracts with exogenous SUMO-1 protein. Inhibition of SUMO modification by a
      dominant-negative mutant of the SUMO-conjugating enzyme Ubc9 (dnUbc9) did not
      detectably alter topoisomerase II activity, but it did increase the amount of
      unmodified topoisomerase II retained on mitotic chromosomes after high salt
      washing. dnUbc9 did not disrupt the assembly of condensed mitotic chromosomes or
      block progression of extracts through mitosis, but it did block the dissociation
      of sister chromatids at the metaphase-anaphase transition. Together, our results
      suggest that SUMO conjugation is important for chromosome segregation in metazoan
      systems, and that mobilization of topoisomerase II from mitotic chromatin may be
      a key target of this modification.

PMID- 14597773
TI  - Evidence for a two membrane-spanning autonomous mitochondrial DNA replisome.
AB  - The unit of inheritance for mitochondrial DNA (mtDNA) is a complex nucleoprotein
      structure termed the nucleoid. The organization of the nucleoid as well as its
      role in mtDNA replication remain largely unknown. Here, we show in Saccharomyces
      cerevisiae that at least two populations of nucleoids exist within the same
      mitochondrion and can be distinguished by their association with a discrete
      proteinaceous structure that spans the outer and inner mitochondrial membranes.
      Surprisingly, this two membrane-spanning structure (TMS) persists and self
      replicates in the absence of mtDNA. We tested whether TMS functions to direct the
      replication of mtDNA. By monitoring BrdU incorporation, we observed that actively
      replicating nucleoids are associated exclusively with TMS. Consistent with TMS's
      role in mtDNA replication, we found that Mip1, the mtDNA polymerase, is also a
      stable component of TMS. Taken together, our observations reveal the existence of
      an autonomous two membrane-spanning mitochondrial replisome as well as provide a
      mechanism for how mtDNA replication and inheritance may be physically linked.

PMID- 14597775
TI  - A function for the mitochondrial chaperonin Hsp60 in the structure and
      transmission of mitochondrial DNA nucleoids in Saccharomyces cerevisiae.
AB  - The yeast mitochondrial chaperonin Hsp60 has previously been implicated in
      mitochondrial DNA (mtDNA) transactions: it is found in mtDNA nucleoids associated
      with single-stranded DNA; it binds preferentially to the template strand of
      active mtDNA ori sequences in vitro; and wild-type (rho+) mtDNA is unstable in
      hsp60 temperature-sensitive (ts) mutants grown at the permissive temperature.
      Here we show that the mtDNA instability is caused by a defect in mtDNA
      transmission to daughter cells. Using high resolution, fluorescence deconvolution
      microscopy, we observe a striking alteration in the morphology of mtDNA nucleoids
      in rho+ cells of an hsp60-ts mutant that suggests a defect in nucleoid division.
      We show that rho- petite mtDNA consisting of active ori repeats is uniquely
      unstable in the hsp60-ts mutant. This instability of ori rho- mtDNA requires
      transcription from the canonical promoter within the ori element. Our data
      suggest that the nucleoid dynamics underlying mtDNA transmission are regulated by
      the interaction between Hsp60 and mtDNA ori sequences.

PMID- 14597776
TI  - Mice with defects in HB-EGF ectodomain shedding show severe developmental
      abnormalities.
AB  - Heparin-binding EGF-like growth factor (HB-EGF) is first synthesized as a
      membrane-anchored form (proHB-EGF), and its soluble form (sHB-EGF) is released by
      ectodomain shedding from proHB-EGF. To examine the significance of proHB-EGF
      processing in vivo, we generated mutant mice by targeted gene replacement,
      expressing either an uncleavable form (HBuc) or a transmembrane domain-truncated
      form (HBdeltatm) of the molecule. HB(uc/uc) mice developed severe heart failure
      and enlarged heart valves, phenotypes similar to those in proHB-EGF null mice. On
      the other hand, mice carrying HBdeltatm exhibited severe hyperplasia in both skin
      and heart. These results indicate that ectodomain shedding of proHB-EGF is
      essential for HB-EGF function in vivo, and that this process requires strict
      control.

PMID- 14597777
TI  - Kinematics of the uterus: cine mode MR imaging.
AB  - Cine mode magnetic resonance (MR) imaging has allowed evaluation of kinematics of
      the pelvis. Visualization of dynamic changes under strain facilitates evaluation
      of prolapses and adhesions between organs. The uterus, an organ of smooth muscle,
      has an inherent contractility that characterizes it as different from other
      visceral organs. This sustained contraction has occasionally been shown on static
      images as a finding masquerading as a leiomyoma or as adenomyosis. Cine mode MR
      imaging clearly shows the configuration of the myometrium during these dynamic
      changes, as well as its signal intensity during contractions. Uterine
      peristalsis, the subtle and rhythmic contractions of the inner myometrium, is
      also clearly identifiable on cine mode images as a wavy movement of the
      endometrium and/or inner myometrium. The direction and frequency of uterine
      peristalsis are different in each of the menstrual cycle phases and are thought
      to have important roles in uterine function, such as in fertility and menstrual
      blood discharge. Elucidation of these kinematics of the uterus will help in the
      evaluation of static MR images and study of the physiology of the uterus. Cine MR
      imaging is a novel technique for diagnosis and evaluation of the pelvic organs,
      especially the uterus.

PMID- 14597778
TI  - Folic acid and birth defects.

PMID- 14597779
TI  - Factors influencing the selection of surgical specialty among Pakistani medical
      graduates.
AB  - CONTEXT: The delineation between selection of surgery and non-surgery residency
      programmes could provide a pragmatic view of the influences on medical graduates'
      careers. This would also help coordinators and educators of residency programmes
      in surgery to further understand the dynamics of specialty selection. AIMS: To
      identify the different factors that influence the graduates to select surgical
      specialties in Pakistan. SETTINGS AND DESIGNS: A cross-sectional survey was
      conducted in 4 teaching hospitals of Karachi between July 1999 and January 2001.
      SUBJECTS AND METHODS: A total of 455 residents in 1-5 years of residency
      programmes were contacted. Three hundred and forty-one residents consented to the
      interview. Residents who were registered both with the College of Physicians and
      Surgeons of Pakistan (CPSP) and the Post Graduate Medical Education (PGME) office
      of the selected hospitals were included in this study. STATISTICAL METHOD USED:
      Logistic regression analysis. RESULTS: Final multivariate analysis identified 4
      factors that remained significantly associated with the selection of surgical
      specialty: deriving gratification from direct patient care (adjusted odds ratio
      [aOR] = 5.79; 95% confidence interval [CI]: 1.24, 26.99), procedure-based medical
      practice (aOR = 2.85; 95% CI: 1.23, 6.61), nature of clinical problems (aOR =
      3.39; 95% CI: 1.47, 7.84), and lack of consideration of stress during
      professional work (aOR = 2.27, 95%CI: 1.25, 4.13). CONCLUSIONS: Direct patient
      care is perceived to be an integral part of surgery residency and immediate
      patient outcome is a positive influence in selecting surgical specialty. The
      inclination towards surgery appeared to be determined by the type of procedures
      and technical skills involved in its practice. The nature of clinical problems is
      an important determinant of the choice of specialty. Stress was not perceived to
      be an important influencing factor for those who decided to select surgical
      specialties.

PMID- 14597780
TI  - Topiramate in the treatment of myoclonic-astatic epilepsy in children: a
      retrospective hospital audit.
AB  - BACKGROUND: Myoclonic-Astatic Epilepsy (MAE) usually starts before five years of
      age and is associated with very frequent seizures and is highly resistant to
      treatment. AIM: To investigate the outcome of adjunctive topiramate (TPM) therapy
      in children with a diagnosis of MAE syndrome. SUBJECTS AND METHODS: In an
      outpatient setting, case notes of 27 children who received TPM were retrieved and
      analysed. RESULTS: Records of 6 children with MAE, who were experiencing 2-8
      atonic seizures daily before starting TPM were studied. Improvement was noted
      after addition of TPM (mean dose at steady-state 7.4+/-2.5mg/kg/day) to the
      regimen of 1-3 anti-epileptic drugs they were receiving concurrently. All but one
      child improved following the titration period: one had 50-80% improvement in the
      frequency of atonic seizures and three had over 80% improvement. However, one
      child who showed over 80% improvement and was free of atonic seizures, later
      developed increased frequency of other seizure types. In one child there was no
      significant improvement. Improvement has been sustained for over 6 months in
      three patients and over 4 months in one; three have continued TPM. TPM was
      stopped in three patients (reduction in seizure control/no improvement).
      CONCLUSIONS: This study supports the efficacy of TPM in controlling atonic
      seizures in MAE and indicates that it should be considered as an add-on drug in
      the management of this 'difficult-to-treat' epileptic syndrome.

PMID- 14597781
TI  - Estimation of subjective stress in acute myocardial infarction.
AB  - BACKGROUND AND AIMS: Mental stress is considered to be a precipitating factor in
      acute coronary events. We aimed to assess the association of subjective or
      'perceived' mental stress with the occurrence of acute coronary events. SETTINGS
      AND DESIGN: Prospective case-control survey was carried out in a referral
      teaching hospital. SUBJECTS & METHODS: Consecutive patients with acute myocardial
      infarction and ST elevation on electrocardiogram who were admitted to the
      Coronary Care Unit of a referral teaching hospital were enrolled in the study as
      cases. Controls were unmatched and were enrolled from amongst patients with
      coronary artery disease who did not have recent acute coronary events. Subjective
      Stress Functional Classification (SS-FC) for the preceding 2-4 weeks was assessed
      and assigned four grades from I to IV as follows: I - baseline, II - more than
      usual but not affecting daily routine, III - significantly high stress affecting
      daily routine and IV - worst stress in life. STATISTICAL ANALYSIS: Proportions of
      different characteristics were compared using chi-square test with Yates
      continuity correction. Student's unpaired t test was applied for mean age. 'p'
      value of < 0.05 was considered statistically significant. RESULTS: SS-FC could be
      reliably (99%) and easily assessed. Eighty (53%) of the total 150 patients with
      acute MI reported 'high' levels of stress (stress class III and IV). This is in
      contrast to only 30 (20%) of 150 healthy controls reporting high stress for the
      same period (p value < 0.001). CONCLUSION: Patients with acute myocardial
      infarction report a higher subjective mental stress during 2 to 4 weeks preceding
      the acute coronary event.

PMID- 14597782
TI  - Effect of epidural morphine on minimum alveolar concentration of isoflurane in
      humans.
AB  - BACKGROUND AND AIMS: The anaesthetic potency of volatile anaesthetic agents is
      measured by the minimum alveolar concentration (MAC) required to suppress
      response in 50% of subjects. We studied the effect of epidural morphine on MAC of
      isoflurane in humans. SETTINGS AND DESIGN: A prospective single-blind study
      designed to study the effect of epidural morphine on MAC of isoflurane. SUBJECTS
      AND METHODS: Forty-eight patients were randomly divided into two groups - Group I
      patients received 3 mg morphine in 10 ml saline, and Group II patients received
      10 ml saline epidurally. Anaesthesia was induced with isoflurane in oxygen and
      nitrous oxide. Later nitrous oxide was discontinued and MAC of isoflurane
      determined using modified Dixon's method of sequential sampling. RESULTS:
      Epidural morphine resulted in a significant reduction in MAC of isoflurane, 0.98
      vs. 1.14 in control group (p<0.05). CONCLUSIONS: Epidural administration of 3 mg
      morphine in 10 ml saline decreased the MAC of isoflurane.

PMID- 14597783
TI  - Duodenal tuberculosis: radiological features on barium studies and their clinical
      correlation in 28 cases.
AB  - BACKGROUND: A retrospective analysis of 28 cases of duodenal tuberculosis (TB)
      was done to evaluate radiological findings and their value in the diagnosis of
      the disease. SUBJECTS AND METHODS: Upper gastrointestinal and small bowel series
      of 28 patients with duodenal tuberculosis were analysed for radiological
      findings. The diagnosis of duodenal TB was confirmed by surgery and biopsy in 18,
      on the basis of radiological findings and response to treatment in 9, and on the
      basis of findings on upper gastrointestinal scopy and biopsy in 1 patient.
      RESULTS: The study included 28 patients (14 males, 14 females). The mean age was
      32.1 (range 5-65). Twenty-three (82.2%) patients presented with obstructive
      symptoms while five manifested with dyspeptic symptoms. Of the latter, 4 had
      ulcerations in the third and fourth parts of the duodenum. In the remaining
      patient, the mucosa of the duodenum could not be clearly visualised. Two patients
      had extrinsic impression at the D2-D3 and D3-D4 segments. In 23 patients with
      obstructive symptoms, 18 demonstrated luminal narrowing of varying degrees and 5
      had a sharp band-like cut-off at the third part of the duodenum. Of the 18
      patients with luminal narrowing, 13 had extrinsic compression, 12 had proximal
      dilatation and 14 had ulcerations mainly in the second and third parts of the
      duodenum. Biliary involvement was seen in 3 patients without any signs or
      symptoms directly referable to the biliary involvement. CONCLUSION: Though
      duodenal TB lacks specific radiological features, barium studies help to localise
      and define the area of narrowing and ulcerations and help to confirm the presence
      of lymph nodes causing compression of the duodenum.

PMID- 14597784
TI  - Prognostic implications of white cell differential count and white cell
      morphology in Malaria.
AB  - BACKGROUND: Malaria is of immense importance amongst the tropical diseases in
      India. There is a need to develop newer diagnostic aids and research is necessary
      to identify new prognostic markers for prediction of the course and
      complications. AIMS: To evaluate the white cell differential count and morphology
      in Plasmodium vivax and Plasmodium falciparum malaria and study their prognostic
      utility. SUBJECTS AND METHODS: Two hundred and sixty-four adult patients in the
      age range of 20 to 65 years presenting to the hospital over a period of 4 months
      with clinical features of malaria and a positive peripheral smear examination
      were studied. RESULTS: No statistically significant difference was noted in the
      white blood cell (WBC) count and neutrophil count in P.vivax versus P. falciparum
      malaria. Band cells were more frequently noted in P. falciparum malaria than in
      P.vivax malaria (p < 0.0001). Toxic granulation of the neutrophils was noted in
      9.5% of the patients and exclusively in P. falciparum malaria. Presence of toxic
      granulation of the polymorphs in subjects with P. falciparum malaria was
      significantly associated with anaemia (p=0.019), jaundice, cerebral involvement,
      adult respiratory distress syndromes, renal dysfunction and death (p < 0.0001 for
      all these parameters). CONCLUSION: Band cells were seen in P. vivax and P.
      falciparum malaria, although in higher numbers in P. falciparum malaria. Toxic
      granulation of the neutrophils was noted only in the presence of P. falciparum
      malaria in this study and correlated with severity.

PMID- 14597785
TI  - Cancer risk and diet in India.
AB  - India is a developing country with one of the most diverse populations and diets
      in the world. Cancer rates in India are lower than those seen in Western
      countries, but are rising with increasing migration of rural population to the
      cities, increase in life expectancy and changes in lifestyles. In India, rates
      for oral and oesophageal cancers are some of the highest in the world. In
      contrast, the rates for colorectal, prostate, and lung cancers are one of the
      lowest. Studies of Indian immigrants in Western societies indicate that rates of
      cancer and other chronic diseases, such as coronary heart disease and diabetes,
      increase dramatically after a generation in the adopted country. Change of diet
      is among the factors that may be responsible for the changing disease rates. Diet
      in India encompasses diversity unknown to most other countries, with many dietary
      patterns emanating from cultural and religious teachings that have existed for
      thousands of years. Very little is known, however, about the role of the Indian
      diet in causation of cancer or its role, if any, in prevention of cancer,
      although more attention is being focused on certain aspects of the Indian diet,
      such as vegetarianism, spices, and food additives. Of particular interest for
      cancer prevention is the role of turmeric (curcumin), an ingredient in common
      Indian curry spice. Researchers also have investigated cumin, chilies, kalakhar,
      Amrita Bindu, and various plant seeds for their apparent cancer preventive
      properties. Few prospective studies, however, have been conducted to investigate
      the role of Indian diet and its various components in prevention of cancer. From
      a public health perspective, there is an increasing need to develop cancer
      prevention programs responsive to the unique diets and cultural practices of the
      people of India.

PMID- 14597786
TI  - Antioxidant micronutrients in the prevention of age-related diseases.
AB  - The role and functions of antioxidant micronutrients such as ascorbate (vitamin
      C), a-tocopherol (vitamin E) and carotenoids that are provided through the diet
      in aging and in the prevention of age-related diseases are discussed in the
      present work. In general, a healthy lifestyle involving regular exercise and
      avoidance of tobacco or alcohol abuse are the key to the prevention of several
      age-related diseases including cardiovascular diseases, dementia and cancer. A
      balanced and regular nutrition with at least five portions of fruit and
      vegetables per day is a critical constituent of such a healthy lifestyle.

PMID- 14597787
TI  - Can we prevent Parkinson's and Alzheimer's disease?
AB  - Parkinson's disease (PD) and Alzheimer's (AD) are major progressive neurological
      disorders, the risk of which increases with advancing age (65 years and over). In
      familial cases, however, early onset of disease (about 35 years) is observed. In
      spite of extensive basic and clinical research on PD and AD, no preventive or
      long-term effective treatment strategies are available. Several studies have
      indicated that oxidative stress is a major risk factor for the initiation and
      progression of sporadic PD and AD. Even a-synuclein and b-amyloid fragments that
      are associated with the PD and AD, respectively, mediate part of their action via
      oxidative stress. Therefore, reducing oxidative stress appears to be a rational
      choice for the prevention and reduction in the rate of progression of these
      neurological disorders. This review provides a brief description of the
      epidemiology and pathogenesis of PD and AD, and the scientific rationale for the
      use of multiple antioxidants in the prevention of these neurological diseases.

PMID- 14597788
TI  - Primary giant cell malignant fibrous histiocytoma of the kidney with staghorn
      calculi.
AB  - Malignant fibrous histiocytomas (MFH) as primary renal tumours are rare, with
      less than 50 cases described in the literature. We report a case of primary renal
      MFH of giant cell type in a 56-year-old man, who presented with bilateral dull
      flank pain, intermittent gross haematuria and body weight loss (6 kg in 3
      months). Intravenous urography, computerized tomography (CT) and magnetic
      resonance image (MRI) showed right ureteral stones with mild hydronephrosis, and
      a solid mass at the lower pole of the left kidney associated with staghorn
      calculi, as well as tumour thrombi in the left renal vein and inferior vena cava.
      Left radical nephrectomy and evacuation of tumour thrombi from the left renal
      vein and inferior vena cava were performed. Histopathologic examination revealed
      malignant fibrous histiocytoma (MFH) of giant cell type. To the best of our
      knowledge, this is the first report of primary renal MFH associated with staghorn
      calculi.

PMID- 14597789
TI  - Distal tibial transphyseal osteotomy for ankle varus deformity in an operated
      case of clubfoot.
AB  - Ankle varus deformity arises due to a number of congenital and acquired causes
      leading to significant functional debility in the patients, especially children.
      We report a less commonly used technique, the transphyseal osteotomy of distal
      tibia, for the correction of varus deformity of the ankle joint in a thirteen
      year-old boy. Full correction of the deformity could be achieved using this
      technique. The patient is fully functional with normal gait. No recurrence was
      detected at follow-up visit 26 months later.

PMID- 14597790
TI  - Diffuse large B cell lymphoma in a patient with hypocomplementemic urticarial
      vasculitis.
AB  - Hypocomplementemic urticarial vasculitis (HUV) is known to be associated with
      malignancies. Urticarial vasculitis has been linked to lymphomas, but to our
      knowledge, the association of HUV and non-Hodgkin lymphoma has not been described
      so far. A patient with HUV who developed 10 years later a diffuse large B cell
      lymphoma is reported here.

PMID- 14597791
TI  - Atrial flutter following a wasp sting.
AB  - Wasp stings have been associated with a wide variety of local and systemic
      reactions including, rarely, tachyarrhythmias. We discuss a case of atrial
      flutter occurring in a 64-year-old man following a single sting in the absence of
      anaphylaxis. The pathogenesis is discussed and the literature reviewed.

PMID- 14597792
TI  - Clinical photography: a guide for the clinician.
AB  - Clinicians might not always have available the services of a professional medical
      photographer, but if a standardised approach is followed those who take their own
      clinical photographs can achieve acceptable results. This article offers guidance
      to the clinician on consistent lighting, exposure, patient positioning, linear
      scale, perspective, depth of field, and background. Advice is given on equipment
      and materials, including digital and conventional cameras, flash (strobe), films,
      and processing choices. Consistency of approach is emphasised - it is not
      acceptable to use photographic tricks to enhance the appearance of clinical
      outcomes. Rather, care should be taken to ensure that the only changes among
      clinical photographs taken over time are in the patient. Photographs should be
      stored and presented appropriately for their use and images for publication
      should be prepared according to the instructions to authors. Digital images for
      publication should be sized appropriately for the final reproduction size.

PMID- 14597793
TI  - The nine flavours of open access scholarly publishing.

PMID- 14597794
TI  - Choroidal metastasis from an occult primary.

PMID- 14597795
TI  - Asterixis.

PMID- 14597796
TI  - Optic disc drusen.

PMID- 14597797
TI  - Angiomyolipoma of kidney as a part of tuberous sclerosis complex.

PMID- 14597798
TI  - Bronchopulmonary sequestration.

PMID- 14597799
TI  - The heart of structural development: the functional basis of the location and
      morphology of the human vascular pump.

PMID- 14597800
TI  - Gabapentin and propofol for treatment of status epilepticus in acute intermittent
      porphyria.

PMID- 14597801
TI  - Transient segmental spinal myoclonus due to spinal anaesthesia with bupivacaine.

PMID- 14597802
TI  - Fatal potassium dichromate ingestion.

PMID- 14597803
TI  - Informed consent in clinical practice.

PMID- 14597804
TI  - The life and times of George Washington Crile.

PMID- 14597805
TI  - Drug-eluting intra-coronary stents: have we got the magic bullet?

PMID- 14597809
TI  - Permission to care.

PMID- 14597808
TI  - Understanding Wolff-Parkinson-White and preexcitation syndromes.

PMID- 14597811
TI  - Handling an unwelcome comeback: Postpolio syndrome.

PMID- 14597810
TI  - Ziprasidone: Test your drug IQ.

PMID- 14597812
TI  - Help! My patient's illiterate.

PMID- 14597813
TI  - Getting the lowdown on lung cancer.

PMID- 14597815
TI  - How to make nursing research work for you.

PMID- 14597814
TI  - Staying current on defibrillator safety.

PMID- 14597816
TI  - Act FAST with intraosseous infusion.

PMID- 14597817
TI  - Waiting for a miracle.

PMID- 14597818
TI  - Inflammatory bowel disease (IBD).

PMID- 14597819
TI  - Staying a step ahead of migraines.

PMID- 14597820
TI  - Multidrug-resistant microorganisms: still making waves.

PMID- 14597821
TI  - Hip fracture.

PMID- 14597822
TI  - An ode to mentors.

PMID- 14597823
TI  - Should nurses promote cobedding of multiples? Pro.

PMID- 14597824
TI  - Should nurses promote cobedding of multiples? Con.

PMID- 14597825
TI  - Promoting father-friendly healthcare.
AB  - Fathers are taking a more active role in their children's lives and healthcare;
      consequently, healthcare providers need to be more aware of and attentive to
      fathers in clinical encounters. The literature on healthcare provider inclusion
      of fathers is sparse. The focus has been mainly on exhortations to include
      fathers, or has documented treatment of fathers as invisible in healthcare
      settings. While not overtly hostile to fathers, healthcare providers occasionally
      marginalize or ignore them. The purpose of this article is to help healthcare
      providers: (1) become aware of and assess their interactions with fathers and (2)
      be more intentional in their interactions with them. To that end, this article
      includes a self-assessment of one's practice, including the following components:
      introductions, body language, eye contact, obtaining/giving information, and
      beliefs about the role of fathers. Intentional interactions for developing more
      father-friendly healthcare are discussed including both small and large changes,
      guided by the PLISSIT model. Finally, best practices, challenges, issues, and
      resources related to father inclusion in healthcare are described. The major
      issue for providers is to no longer question whether to include fathers, but how.

PMID- 14597826
TI  - Mothers' perceptions of self-care in school-age children with diabetes.
AB  - PURPOSE: To describe mothers' perceptions of the diabetes-related self-care
      abilities and practices of their school-age children with Type 1 diabetes. STUDY
      DESIGN AND METHOD: Qualitative study using the naturalistic inquiry method.
      Mothers of school-age children with diabetes were interviewed by means of a semi
      structured interview guide. The children were between the ages of 11 and 12 and
      had been diagnosed with diabetes for a minimum of 2 years. Twelve mothers were
      interviewed, generating 20 hours of qualitative data. RESULTS: Mothers reported
      that their children with diabetes had learned skills in a predictable sequence,
      were usually motivated by events in the here and now, and did not consistently
      perform all diabetes-related skills of which they were capable. Most of the
      children were becoming embarrassed about having diabetes. There were considerable
      gender differences in the children's self-care development. CLINICAL
      IMPLICATIONS: Nurses can use this study to help with anticipatory guidance for
      parents. It may be helpful for parents to know the sequence in which many
      children learn diabetes-related skills, and to learn that even though a child is
      capable of task performance, he or she may not necessarily be ready for the
      independent practice or daily execution of the skill. Encouraging parents to stay
      involved with their children's self-care practices past the early adolescent
      years may be effective in improving self-care practices, and helping children to
      identify reasons to meet the self-care demands associated with diabetes can be
      beneficial.

PMID- 14597827
TI  - Social and professional support for pregnant and parenting women.
AB  - PURPOSE: A literature review to contrast the role of social and professional
      support in improving maternal and infant outcomes in pregnant and parenting
      women. In addition, recommendations are made for future research and policy and
      program development concerning support needed by pregnant and parenting women.
      DATA SOURCES: Data were limited to published studies. Searches of computerized
      databases, hand searches of journals, and backward searches from reference lists
      of studies were conducted. Nursing, medicine, psychology, public health,
      sociology, and social work literatures were searched (CINAHL, Medline, PsychLit,
      Social Sciences Abstracts, Social Sciences Citation, and Social Work Abstracts).
      STUDY SELECTION: The studies focused on outcomes of social support and
      professional support to pregnant and parenting women. The samples of the studies
      included pregnant women and parenting women up to 2 years postpartum. Studies
      reviewed were conducted in the United States or Canada and included maternal
      and/or infant outcomes. All ages and races of pregnant and parenting women were
      considered. DATA EXTRACTION: Data were extracted from each study concerning the
      theoretical framework, variables, sample, design, measuring instruments,
      interventions, and outcomes. DATA SYNTHESIS: Social support outcomes were
      summarized in paragraphs while a table was used to summarize professional support
      intervention outcomes. CONCLUSIONS: Outcomes associated with specific support
      interventions should be clearly identified, informed by theory, and include
      assisting the pregnant and parenting woman to improve her social support.

PMID- 14597828
TI  - Pregnant adolescents' perspectives of pregnancy.
AB  - PURPOSE: To gain a clearer understanding of teens' perspectives on pregnancy and
      parenting. DESIGN Descriptive qualitative study using grounded theory. METHODS:
      The sample was comprised of 20 pregnant 15- to 19-year-old teens in the second or
      third trimester of pregnancy who planned to keep their child. A taped interview
      of each participant was performed either in the school the teen was attending or
      in the privacy of her home. Data were analyzed using the constant comparative
      method. Interviews were compared with each other to confirm/disconfirm emerging
      themes. RESULTS: The comparison of the data from the 20 interviews resulted in
      themes clearly describing the teens' perceptions of the changes related to
      pregnancy, how they managed these changes, and their views on mothering. Three
      major themes emerged: "The pregnant me--unexpected changes," "Transformed
      relationships," and "Envisioning mothering." CLINICAL IMPLICATIONS: Nurses caring
      for pregnant adolescents who have made the decision to keep their babies should
      carefully assess each individual's strengths, weaknesses, hopes, and goals prior
      to developing a plan of care. Identifying the teens' living situations and
      support from family, father of the baby, and/or friends and recognizing and
      building upon the strengths the teens bring to the pregnancy may influence the
      pregnancy's outcome. Encouraging attendance and participation in programs
      specifically designed for pregnant adolescents and adolescent parents may be a
      helpful strategy for these teens.

PMID- 14597829
TI  - The power of words: examining the linguistic landscape of pediatric nursing.
AB  - The purposes of this article are to increase pediatric nurses' awareness of
      language use and to suggest strategies that foster therapeutic communication for
      the benefit of children and parents. The use of jargon, labels, metaphors, and
      parental expressions of stress are examined from the context of therapeutic
      communication in nursing practice. Evidence of language use is substantiated by
      theory, submissions to a Web site that features narratives from youngsters coping
      with disease and disability, and interactions with children in hospitals.
      Practice recommendations are made for the integration of language that protects
      children's self-esteem.

PMID- 14597830
TI  - How a cost-containment initiative produced recruitment and retention.
AB  - The Maryland Perinatal Education Consortium (MPEC), a 12-hospital education
      initiative, provides basic didactic education for perinatal nurses. The MPEC core
      curriculum integrates patient-specific cultural and age-related considerations
      for both the novice and experienced perinatal nurse. While the primary goal for
      developing the consortium was to maximize use of the nurse educator's time by
      pooling educational resources between participating hospitals, member hospitals
      have discovered that it also resulted in advantageous positioning for recruitment
      and retention of nursing staff. MPEC's pooled turnover rate of 14% is below the
      national average of 16%, resulting in important cost savings and additional staff
      for participating hospitals. This article describes the development of the MPEC
      and uses the Nursing Executive Center's model of turnover costs to describe the
      cost savings and retention impact for various-sized hospitals achieved through
      MPEC's multihospital collaboration in staff development.

PMID- 14597831
TI  - Spam, filters, and children using the Internet.

PMID- 14597832
TI  - Men in OB Nursing.

PMID- 14597833
TI  - Jewish perspectives.

PMID- 14597834
TI  - Cobedding twins.

PMID- 14597835
TI  - Yet more hypertension guidelines: what do they add?

PMID- 14597836
TI  - 2003 World Health Organization (WHO)/International Society of Hypertension (ISH)
      statement on management of hypertension.
AB  - OBJECTIVE: Hypertension is estimated to cause 4.5% of current global disease
      burden and is as prevalent in many developing countries, as in the developed
      world. Blood pressure-induced cardiovascular risk rises continuously across the
      whole blood pressure range. Countries vary widely in capacity for management of
      hypertension, but worldwide the majority of diagnosed hypertensives are
      inadequately controlled. This statement addresses the ascertainment of overall
      cardiovascular risk to establish thresholds for initiation and goals of
      treatment, appropriate treatment strategies for non-drug and drug therapies, and
      cost-effectiveness of treatment. CONCLUSIONS: Since publication of the WHO/ISH
      Guidelines for the Management of Hypertension in 1999, more evidence has become
      available to support a systolic blood pressure threshold of 140 mmHg for even
      'low-risk' patients. In high-risk patients there is evidence for lower
      thresholds. Lifestyle modification is recommended for all individuals. There is
      evidence that specific agents have benefits for patients with particular
      compelling indications, and that monotherapy is inadequate for the majority of
      patients. For patients without a compelling indication for a particular drug
      class, on the basis of comparative trial data, availability, and cost, a low dose
      of diuretic should be considered for initiation of therapy. In most places a
      thiazide diuretic is the cheapest option and thus most cost effective, but for
      compelling indications where other classes provide additional benefits, even if
      more expensive, they may be more cost effective. In high-risk patients who attain
      large benefits from treatment, expensive drugs may be cost effective, but in low
      risk patients treatment may not be cost-effective unless the drugs are cheap.

PMID- 14597837
TI  - Recommendations for prevention, diagnosis and management of hypertension and
      cardiovascular risk factors in sub-Saharan Africa.

PMID- 14597838
TI  - Childhood blood pressure: a window to adult hypertension.

PMID- 14597839
TI  - Pulse pressure and arterial stiffness in type 1 diabetic patients.

PMID- 14597840
TI  - Congenics in the pathway from quantitative trait loci detection to gene
      identification: is that the way to go?

PMID- 14597841
TI  - Polymorphisms in human endothelin-converting enzyme (ECE-1) promoter can modulate
      ECE-1 gene expression.

PMID- 14597842
TI  - Should baroreflex sensitivity be corrected for heart rate?

PMID- 14597843
TI  - Do studies on a sinoaortic denervation model give a clue to the mechanisms of
      cardiovascular and renal damage in hypertension?

PMID- 14597844
TI  - High blood pressure and brain oedema in acute stroke: the relevance of ambulatory
      blood pressure monitoring during the first 24 h after stroke onset.

PMID- 14597845
TI  - Does a routinely measured blood pressure in young adolescence accurately predict
      hypertension and total cardiovascular risk in young adulthood?
AB  - BACKGROUND: It is insufficiently known if routine blood pressure (BP) measurement
      by school doctors has added predictive value for later hypertension and
      cardiovascular risk. OBJECTIVE: To assess whether screening of BP in adolescence
      has additional predictive value to already routinely collected indicators of
      later hypertension and cardiovascular risk. METHODS: In the Dutch city of
      Utrecht, routine BPs and anthropometry were collected from school health records
      of 750 adolescents. In The Hague, standardized repeated BP measurements and
      anthropometry were available for 262 adolescents. Of both cohorts, 998 now young
      adults were recently re-examined. Predictors of adult hypertension, systolic
      blood pressure (SBP) > or = 140 mmHg and/or diastolic blood pressure (DBP) > or =
      90 mmHg) and 10-year cardiovascular risk were analysed by logistic regression and
      area under receiver operator characteristics curve (AUC). RESULTS: A total of 167
      young adults had hypertension. Single adolescent SBP and DBP predicted
      hypertension: odds ratio (OR) 1.04 per mmHg [95% confidence interval (CI): 1.03
      1.06], OR 1.02 (1.00-1.04), respectively, but with little discriminative power.
      Gender, adolescent body mass index (BMI) and age combined predicted hypertension:
      AUC 0.71 (0.67-0.75), which slightly improved by adding SBP: AUC 0.74 (0.70
      0.77); difference in AUC 0.03 (0.002-0.06). SBP exclusively predicted
      hypertension within men: OR 1.03 (1.01-1.04), AUC: 0.59 (0.53-0.65), and within
      women: OR 1.08 (1.05-1.11), AUC 0.74 (0.67-0.82). However, an adolescent BP of >
      or = 120 mmHg did not efficiently detect hypertensive men, while it detected
      57.9% of hypertensive women. Only young adult men had meaningful 10-year
      cardiovascular risks, which only SBP predicted: OR risk score > 95th percentile
      1.04 (1.02-1.07), AUC 0.67 (0.60-0.75). CONCLUSION: A single routine BP
      measurement in adolescent girls efficiently predicts young adult hypertension. In
      adolescent boys, BP predicts young adult 10-year cardiovascular risk.

PMID- 14597846
TI  - Pulse pressure is associated with age and cardiovascular disease in type 1
      diabetes: the Eurodiab Prospective Complications Study.
AB  - OBJECTIVE: Type 1 diabetic individuals are thought to have increased arterial
      stiffness, and are at high risk for cardiovascular disease. However, it is not
      known whether increased arterial stiffness in type 1 diabetes causes
      cardiovascular disease. To explore this issue, the present study investigated the
      association, in type 1 diabetes, of age and pulse pressure, an estimate of
      arterial stiffness, and the influence of the presence of microvascular
      complications on this association. In addition, we determined the association of
      mean arterial pressure and pulse pressure with incident cardiovascular disease.
      METHODS: We studied a cohort of 3250 type 1 diabetic individuals of the EURODIAB
      Prospective Complications Study. Mean age and median follow-up were 33 and 7.4
      years. One hundred and sixty-three individuals developed a first manifestation of
      cardiovascular disease during follow-up. Linear regression analysis was used to
      determine the association of age with pulse pressure. Relative risks of
      cardiovascular disease were estimated by Cox regression analyses adjusted for
      age, sex and mean arterial pressure or pulse pressure.RESULTS In cross-sectional
      analyses, age was associated with pulse pressure (P < 0.001) and this association
      was stronger in the presence of micro- or macroalbuminuria or retinopathy than in
      their absence (interaction for albuminuria, P < 0.001; interaction for
      retinopathy, P < 0.001). In prospective analyses, both mean arterial pressure and
      pulse pressure were associated with cardiovascular disease [adjusted relative
      risks and (95% confidence interval) per 10 mmHg increase were 1.08 (0.94-1.24)
      and 1.09 (0.98-1.21)]. CONCLUSIONS: This study shows an association of age with
      pulse pressure in young type 1 diabetic individuals, which is stronger in the
      presence of microvascular complications. In addition, both mean arterial pressure
      and pulse pressure are associated with incident cardiovascular disease. These
      findings support the concept of early vascular ageing in type 1 diabetes,
      especially in the presence of microvascular complications.

PMID- 14597847
TI  - A comparison of awake-sleep blood pressure variation between normotensive
      Japanese-American and Caucasian women in Hawaii.
AB  - OBJECTIVE: To compare awake-sleep ambulatory blood pressure variation between
      Japanese-American and Caucasian women in Hawaii, specifically determining whether
      Japanese-Americans have reduced dipping of blood pressure during sleep, as is
      found in comparisons of Japanese and US samples. METHODS: Normotensive school
      teachers from East Hawaii who were either of Japanese-American (n = 70) or
      Caucasian (n = 48) ethnicity were recruited. They wore an ambulatory blood
      pressure monitor (Spacelabs 90207) that took measurements every 15 min during
      waking hours and every 30 min during sleep for a 24-h period on a normal workday.
      All subjects provided demographic information and underwent a series of
      anthropometric measurements the day before monitoring. Japanese-American subjects
      also answered questionnaires relating to cultural identity and migration history.
      RESULTS: The Japanese-American women had significantly higher mean diastolic (P <
      0.01) blood pressure during sleep. These ethnic differences in sleep blood
      pressure persisted when analyses controlled for age, body mass index, and the
      waist-hip circumference ratio. There were also significant differences in the
      proportion by which blood pressure dipped from waking to sleeping, with the
      Japanese-American women dipping significantly less than the Caucasian women (P <
      0.05 systolic, P < 0.001 diastolic). CONCLUSIONS: Normotensive Japanese-American
      women have higher sleep pressure, and a smaller awake-sleep dip, in pressure than
      Caucasian women. The relative elevation of blood pressure in Japanese-American
      women during sleep, but not at other times of the day, is similar to the pattern
      seen among Japanese women in Japan.

PMID- 14597848
TI  - Validation and use of the Finometer for blood pressure measurement in normal,
      hypertensive and pre-eclamptic pregnancy.
AB  - OBJECTIVE: Although a large variety of automated blood pressure devices are
      available, only some have been validated for use in clinical practice. The
      British Hypertension Society (BHS) recommends separate validation of automated
      devices in special subgroups, e.g. the elderly and pregnant women. The aim of
      this study was to compare the Finometer (FM) and the earlier validated SpaceLabs
      90207 (SL) with standard auscultatory blood pressure measurements in normal, pre
      eclamptic and hypertensive pregnancy, following the guidelines of the BHS and the
      Association for the Advancement of Medical Instrumentation (AAMI). METHODS: The
      total study group consisted of 123 pregnant women, of whom were 54 normotensive,
      31 pre-eclamptic and 38 hypertensive. Automated readings with the FM and SL were
      compared with auscultatory blood pressure measurements. Bland-Altman plots, BHS
      grades, mean pressure differences and 95% limits of agreement were used for
      analysis. RESULTS: Bland-Altman plots showed a wide scatter of the pressure
      differences between auscultatory and automated measurements. FM achieved BHS
      grades C/D, C/B, D/D and D/D in the total, normotensive, pre-eclamptic and
      hypertensive group, respectively. The AAMI criteria were only met for diastolic
      blood pressure in the normotensive group. For SL almost identical BHS grades and
      95% limits of agreement as compared to our earlier study were found. CONCLUSIONS:
      The accuracy and precision of the Finometer are not sufficient for determination
      of absolute blood pressure levels in individual pregnant women. Our present
      findings on the SpaceLabs 90207 reconfirm our earlier results.

PMID- 14597849
TI  - The G-217A variant of the angiotensinogen gene affects basal transcription and is
      associated with hypertension in a Taiwanese population.
AB  - OBJECTIVE: Polymorphisms of the angiotensinogen (AGT) gene, especially in the
      promoter region, are in linkage concordance and are associated with hypertension.
      In this study, we examined the role of AGT promoter polymorphisms, including G
      217A, A-6G and M235T variants, and their promoter function in essential
      hypertension in Taiwanese populations. DESIGN: An association study was conducted
      to assess the genotype distribution between hypertensive patients and
      normotensive subjects. We also used a transient transfection assay to examine
      basal transcriptional activity of G-217A and A-6G variants in a mammalian cell
      system. METHODS: Hypertensive subjects (390) and normotensive controls (388) of
      Taiwanese ethnicity were genotyped for the AGT G-217A, A-6G and M235T variants.
      Promoter activity was studied by cloning the promoter region (-614 to +41 bp) of
      AGT into the pSEAP2-Basic reporter vector and performing a transient transfection
      assay in HuH7 and HepG2 cells. RESULTS: The G-217A variant of the AGT gene was
      significantly associated with hypertension (P = 0.0047), but the A-6G and M235T
      polymorphisms were not (P = 0.17 and P = 0.33, respectively). Furthermore, the
      recessive model of homozygous genotype (-217AA) conferred a high risk for
      hypertension (odds ratio 3.64) in this population. The -217A variant expressed
      higher transcriptional activity than -217G in vitro. CONCLUSIONS: Our study
      showed a significant association between the -217A variant of the AGT gene and
      hypertension. This variant plays a functional role in basal transcription of AGT,
      and may confer a risk for hypertension in Taiwanese populations.

PMID- 14597850
TI  - Influence of vitamin D receptor gene polymorphisms and 25-hydroxyvitamin D on
      blood pressure in apparently healthy subjects.
AB  - BACKGROUND: There are no studies that relate BsmI polymorphism of the vitamin D
      receptor (VDR) gene and with vitamin D to blood pressure (BP). OBJECTIVE: To
      analyze if this polymorphism and 25-hydroxyvitamin D levels (25OHD3) influence BP
      in a population of healthy subjects. DESIGN: Transversal study on healthy
      population. Stepwise multiple regression analysis was performed to assess the
      association of BP with several clinical and biochemical data. SETTING: Industrial
      employees, blood donors, and army cadets from Lleida, Spain were recruited in
      October 2001. INDIVIDUALS: A total of 590 apparently healthy subjects (260 males
      and 330 females). MEASUREMENTS: Systolic blood pressure (SBP) and diastolic blood
      pressure (DBP) were determined as the mean of three measurements. We also
      included age, gender, body mass index (BMI), serum levels of creatinine, calcium,
      phosphorus, intact parathyroid hormone (by two-site chemiluminometric assay), 25
      hydroxyvitamin D (by radioimmunoassay) and BsmI genotype. RESULTS: Since gender
      was strongly associated with both SBP and DBP, a separate analysis was performed
      for men and women. In males, SBP was associated with BMI, 25OHD3 (beta: 0.37, P <
      0.000) and genotype (beta: -4.1, P < 0.001); and DBP with 25OHD3 (beta: 0.19, P <
      0.008) and age. SBP was higher in men with bb genotype than in the other
      genotypes (P < 0.006). Moreover, there was a statistically significant positive
      correlation between 25OHD3 and both SBP (r: 0.53, P < 0.002) and DBP (r: 0.48, P
      < 0.005) in men with genotype BB. In women, neither 25OHD3 nor genotype were
      associated with BP levels. CONCLUSIONS: BsmI polymorphism of the VDR gene
      influences BP in healthy men. A positive relationship between serum 25
      hydroxyvitamin D levels and BP is present only in men with the BB genotype.

PMID- 14597851
TI  - Substitution mapping of a blood pressure quantitative trait locus to a 2.73 Mb
      region on rat chromosome 1.
AB  - OBJECTIVE: To improve the localization of a blood pressure quantitative trait
      locus (BP QTL) on rat chromosome (RNO) 1. METHODS: Congenic substrains were
      derived from the progenitor congenic strains S.LEW(D1Mco4X1) and S.LEW(D1Mco4X5)
      which previously localized a BP QTL (region 2) to a 17cM interval on RNO1. The
      newly developed congenic substrains, along with control Dahl salt-sensitive (S)
      rats were fed a 2% NaCl diet for 24 days before their BP was compared by both
      tail-cuff and radiotelemetry methods. RESULTS: By comparing BP of these congenic
      substrains to that of S rats, we have refined the location of the BP QTL2 region
      to a 2.73 Mb genomic interval that contains 19 annotated genes in the latest rat
      genome assembly (version 2.1). Slc9a3, the gene encoding the Na(+)/H(+) exchanger
      3, originally a candidate gene in the BP QTL2 region, is excluded based on its
      map location. CONCLUSION: Substitution mapping was used to reduce a BP QTL on
      RNO1 from 17 centimorgans (cM) to approximately 1.4 cM (= 2.73 Mb). This region
      now contains 19 annotated rat candidate genes.

PMID- 14597852
TI  - The A1166C polymorphism of the AT1 receptor gene is associated with collagen type
      I synthesis and myocardial stiffness in hypertensives.
AB  - OBJECTIVES: We have investigated whether the A1166C polymorphism of the
      angiotensin II type 1 (AT1) receptor gene modulates the effects of angiotensin II
      on collagen type I turnover and myocardial stiffness in hypertension. METHODS: We
      studied 255 hypertensive patients before and after 1 year of treatment with
      either losartan (n = 185) or atenolol (n = 70). Serum concentrations of the
      carboxy-terminal propeptide of procollagen type I (PIP) and the carboxy-terminal
      telopeptide of collagen type I (CITP), markers of extracellular collagen type I
      synthesis and degradation, respectively, were measured by specific
      radioimmunoassays. Left ventricular chamber stiffness (KLV), was determined from
      the deceleration time of the early mitral filling wave, as measured by Doppler
      echocardiography. Hypertensives were genotyped by polymerase chain reaction and
      divided in two subgroups: AA (n = 126) and AC/CC (n = 129). RESULTS: Baseline PIP
      and KLV were increased (P < 0.01) in AA hypertensives compared with AC/CC
      hypertensives. No changes in baseline CITP were observed between the two
      subgroups of hypertensives. Confounding factors were similar between the two
      subgroups of hypertensives. Administration of losartan was associated with
      reduction (P < 0.01) in PIP and KLV in AA hypertensives but not in AC/CC
      hypertensives. Treatment with atenolol did not change PIP and KLV in either
      subgroup of hypertensives. No changes in CITP were observed with the two
      treatments. CONCLUSION: These findings suggest that the A1166C polymorphism of
      the AT1 receptor gene is associated with collagen type I synthesis and myocardial
      stiffness in patients with hypertensive heart disease.

PMID- 14597853
TI  - Effects of angiotensin II on nitric oxide generation in growing and resting rat
      aortic endothelial cells.
AB  - OBJECTIVES: To assess the effects of angiotensin II (ang II) and its receptors on
      nitric oxide (NO) production and endothelial NO synthase (eNOS) activity and
      expression with respect to rat aortic endothelial cell (RAEC) growth. To also
      assess whether an intact endothelium is required for ang II activity. METHODS:
      RAEC were treated with different doses of ang II, Ca(2+) ionophore A23187,
      valsartan (an AT(1) receptor inhibitor) or PD-123319 (an AT(2) receptor
      inhibitor) alone or in combination for 24 h before measuring nitrite levels by
      Griess reaction as an index of NO production and eNOS activity by L-[3H]-arginine
      to L-[3H]-citrulline conversion assay. eNOS mRNA and protein expressions were
      determined by Northern and Western analyses, respectively. The requirement of
      endothelium for ang II-mediated relaxant/contractile effects was investigated by
      isometric tension studies. RESULTS: NO production and eNOS activity/expression
      were almost two-fold greater in proliferating RAEC. Ang II or Ca(2+) ionophore
      A23187 enhanced NO production in proliferating and confluent RAEC without
      altering the fold-difference in basal NO release. Both valsartan and PD-123319
      significantly diminished NO production in RAEC treated with ang II but not Ca(2+)
      ionophore A23187 while NG-nitro-L-arginine (L-NNA, 10 micromol/l) equally
      decreased NO generation in response to both stimulators. L-NNA, valsartan and PD
      123319 also abolished endothelium-dependent vasorelaxant responses to ACh and
      Ca(2+) ionophore A23187 in the presence of ang II. Sodium nitroprusside (SNP), a
      NO donor, increased endothelium-independent vasorelaxant responses that were
      augmented by valsartan but not L-NNA or PD-123319 in the presence of ang II.
      CONCLUSIONS: Ang II induces vascular NO production through endothelial AT(1) and
      AT(2)-receptors. This may be beneficial in counterbalancing its vasoconstrictor
      effect on vascular smooth muscle cells.

PMID- 14597854
TI  - Infectious and inflammatory stimuli decrease endothelial nitric oxide synthase
      activity in vitro.
AB  - BACKGROUND: Perturbation of iron metabolism, especially the increase of serum
      ferritin levels, is often associated with both inflammation and hypertension.
      Changes in iron availability can affect an important regulator of vascular tone,
      the endothelial nitric oxide synthase (eNOS), activated by a heme-dependent
      dimerization. OBJECTIVE: To study the regulation of the anti-hypertensive eNOS in
      human endothelial cells, in correlation with iron metabolism alterations and
      stimuli triggering them in vivo, such as inflammation or infection. DESIGN: Cells
      were treated with stimuli mimicking infection or inflammation [lipopolysaccharide
      (LPS) and/or tumor necrosis factor alpha (TNFalpha)]. and iron shortage
      (succinylacetone and desferrioxamine). The effect on eNOS expression and
      activation was evaluated, as well as ferritin content. METHODS: eNOS protein
      expression was evaluated by separating the monomeric from the active dimeric form
      by low-temperature sodium dodecyl sulphate poly-acrylamide gel electrophoresis
      (SDS-PAGE), and mRNA was analyzed by semi-quantitative reverse transcriptase (RT)
      polymerase chain reaction (PCR). As for LPS and TNFalpha, eNOS monomer decreased
      already after a 72-h treatment and further at 144 h, whereas the down-regulation
      of the dimer was slower, peaking at 144 h. Succinylacetone and desferrioxamine
      were effective only at 144 h. The mRNA levels were increasingly reduced after
      incubation, more markedly by LPS and TNFalpha together, whereas succinylacetone
      and desferrioxamine had no effect on transcription. We found that endothelial
      cells are not the source of increased ferritin production. CONCLUSIONS: The
      results of this study suggest a down-regulating effect of infectious and
      inflammatory stimuli on eNOS expression, both at the mRNA level and protein
      expression or stability and dimerization, enhanced by heme and iron shortage, and
      indicate eNOS as a possible link between infection and hypertension.

PMID- 14597855
TI  - Regulation of the major isoform of human endothelin-converting enzyme-1 by a
      strong housekeeping promoter modulated by polymorphic microsatellites.
AB  - BACKGROUND: Human endothelin-converting enzyme (ECE)-1, the key enzyme in
      endothelin biosynthesis, shows broad cell and tissue expression within the
      cardiovascular system. Expression of ECE-1c, which represents the major ECE-1
      isoform, is directed by an alternative promoter, but the mechanisms of ECE-1c
      promoter regulation are largely unknown. As ECE-1c transcription is initiated
      from several start sites, we hypothesized that the ECE-1c promoter functions as a
      housekeeping promoter. OBJECTIVE: To investigate the putative housekeeping
      function of the ECE-1c promoter in vascular endothelial cells, which represent a
      main site of its expression. RESULTS: Using promoter reporter assays, gel shift
      and supershift assays, we have demonstrated, in human endothelial EA.hy926 cells,
      functionality of cis-acting elements for binding of the CAAT-box binding protein
      NF-YB, GATA-2) E2F-2, and a GC-box binding factor, which are spatially associated
      with transcriptional start sites of ECE-1c. In the more upstream promoter region
      we have identified three highly polymorphic dinucleotide repeats, 5'-(CA)n, (CG)n
      and 3'-(CA)n, which strongly affected promoter function in endothelial EA.hy926
      cells (2.7-fold activation comparing the most active to the least active allele)
      and, in a similar manner, in human neuronal KELLY cells. Finally, by in-vitro
      methylation, we were able to achieve strong suppression of the ECE-1c promoter
      activity in endothelial cells. CONCLUSION: Our results provide a molecular
      explanation for constitutive expression of ECE-1c mRNA. Modulation by genetic and
      epigenetic mechanisms as revealed in our study may account for interindividual
      variation of the constitutive endothelin system activity in humans and thus
      influence individual predisposition to cardiovascular disease.

PMID- 14597856
TI  - Left ventricular ejection time: a potential determinant of pulse wave velocity in
      young, healthy males.
AB  - OBJECTIVE: Pulse wave velocity (PWV) is a classic marker of vascular stiffness.
      Recent studies showed that heart rate is an important determinant of PWV. The
      purpose of this study was to evaluate the role of myocardial function in
      determining PWV under resting conditions and under adrenergic stimulation. DESIGN
      AND METHODS: Hemodynamic parameters were investigated under resting conditions in
      102 young, healthy males and under stimulation of either beta- or alpha(2)
      adrenoceptors in six young, healthy males. PWV was determined from pressure
      tracing over the carotid and femoral artery. Central hemodynamics were assessed
      by impedance cardiography and systolic time intervals. Simple (r) and multiple
      (beta) regression analyses were used to assess the relationships between PWV and
      hemodynamic parameters. RESULTS: Under resting conditions, PWV was correlated to
      age (beta = 0.259, P = 0.0052), diastolic blood pressure (beta = 0.279, P =
      0.0072) and left ventricular ejection time (beta = -0.314, P = 0.0277). Under
      alpha(2)-adrenergic stimulation PWV was only correlated to diastolic blood
      pressure (DBP) (beta = 0.806, P = 0.0020). Under beta-adrenergic stimulation PWV
      was only correlated to left ventricular ejection time index (r = -0.52, P =
      0.0325). CONCLUSIONS: Left ventricular ejection time may be an important
      determinant of pulse wave velocity under resting and adrenergic conditions in
      young, healthy males. Further studies are needed to evaluate this relationship in
      other populations including females and patients with cardiovascular disease.

PMID- 14597857
TI  - A method for heart rate-corrected estimation of baroreflex sensitivity.
AB  - OBJECTIVE: The relationship between the prevailing heart rate (HR) and the
      baroreflex sensitivity (BRS) is described in the present study together with a
      method for individual HR-corrected estimations of BRS. DESIGN: HR and BRS,
      determined with the sequence method, were measured in ten young healthy subjects
      during rest, stress, standing and bicycle exercise, i.e. at a wide range of HRs.
      RESULTS: BRS decreased exponentially with increasing HR. The relationship between
      the natural logarithm of BRS and HR was linear in each individual and could be
      described by the equation of a straight line. The equation describing the
      individual BRS-HR relationship could be derived either from BRS and HR measured
      during steady-state conditions or from the slope and average HR of the individual
      sequences occurring throughout the experimental protocol. The latter method was
      preferable since it did not require recordings during steady-state conditions. In
      order to eliminate the influence of differences in HR on BRS when comparing BRS
      between subjects, the equation describing the individual BRS-HR relationship was
      used to calculate BRS at a HR of 60 bpm, BRS(60), which ranged from 9.5 to 30.1
      ms/mmHg for the 10 subjects. CONCLUSIONS: Considering the dramatic effect of a
      small difference in HR on BRS, especially at lower HRs, BRS should be estimated
      at a wide range of HRs in order to determine the HR-corrected BRS from the
      individual HR-BRS relationship. Otherwise, comparisons of BRS between different
      individuals, study groups or following drug treatment or other interventions
      would be highly dependent on differences in HR and thereby easily misinterpreted.

PMID- 14597858
TI  - Inflammation is involved in the organ damage induced by sinoaortic denervation in
      rats.
AB  - OBJECTIVE: The present study was designed to test the hypothesis that
      inflammation is involved in the end-organ damage (EOD) induced by sinoaortic
      denervation (SAD) in rats. METHOD: SAD was performed in male Sprague-Dawley rats
      at the age of 10 weeks. Under anaesthesia, aortic nerves were cut and the sinus
      region of the carotid artery was stripped and painted with 10% phenol.
      Pathological evaluation of EOD and the determination of plasma or tissue levels
      of the factors related to inflammation, including thromboxane B2 (TXB2)
      interleukin-1 (IL-1), tumour necrosis factor alpha (TNF-alpha) and reactive
      oxygen species (ROS) were performed at 16 weeks after SAD. Pathological
      evaluation of EOD included heart weight ratio, myocardial and blood vessel
      hydroxyproline and collagen volume fraction, glomerular injury score and number
      of infiltrating inflammatory cells. Indomethacin (20 mg/kg per day, orally) or
      vitamin E (100 mg/kg per day, orally) was administered for 12 weeks, beginning
      from 4 weeks after SAD, to observe their effects on SAD-induced EOD. RESULTS:
      There were significant fibrosis and inflammatory infiltration in the myocardium
      and blood vessels, represented by higher hydroxyproline and collagen volume
      fraction, and a large amount of inflammatory cells in the tissues of SAD rats.
      Heart weight and kidney glomerular injury score were significantly higher in SAD
      than in sham-operated rats. Plasma TXB2, TNF-alpha, IL-1 and tissue ROS increased
      significantly after SAD. Indomethacin and vitamin E significantly decreased the
      contents of some factors related to inflammation in SAD rats. Both drugs also
      alleviated myocardial and vessel fibrosis, inflammatory infiltration and kidney
      damage. CONCLUSION: Inflammation is involved in the organ damage induced by SAD
      in rats.

PMID- 14597859
TI  - High rate of detection of primary aldosteronism, including surgically treatable
      forms, after 'non-selective' screening of hypertensive patients.
AB  - BACKGROUND: Wide testing of the aldosterone : renin ratio among hypertensive
      individuals has revealed primary aldosteronism to be common, with most patients
      normokalaemic. Some investigators, however, have reported aldosterone-producing
      adenoma to be rare among patients so detected. OBJECTIVE: To test the hypothesis
      that differences among reported studies in the rate of detection of aldosterone
      producing adenoma (as opposed to bilateral adrenal hyperplasia) reflect
      differences in the procedures used for diagnosis of primary aldosteronism, and
      the methods used to identify aldosterone-producing adenomas. METHODS: In the
      newly established Princess Alexandra Hospital Hypertension Unit (PAHHU), we used
      procedures developed by Greenslopes Hospital Hypertension Unit (which reports
      that more than 30% of patients with primary aldosteronism have aldosterone
      producing adenomas) to diagnose primary aldosteronism and determine the subtype.
      All patients with an increased aldosterone : renin ratio (measured after
      correction for hypokalaemia and while the patient was not receiving interfering
      medications) underwent fludrocortisone suppression testing to confirm or exclude
      primary aldosteronism; if they were positive, they underwent genetic testing to
      exclude glucocorticoid-remediable aldosteronism before adrenal venous sampling
      was used to differentiate lateralizing from bilateral primary aldosteronism.
      RESULTS: This approach allowed PAHHU to diagnose, within 2 years, 54 patients
      [only seven (13%) hypokalaemic] with primary aldosteronism. All tested negative
      for glucocorticoid-remediable aldosteronism. Aldosterone production was
      lateralized to one adrenal in 15 patients (31%; only six hypokalaemic) and was
      bilateral in 34 (69%; all normokalaemic) of 49 patients who underwent adrenal
      venous sampling. Among patients with lateralizing adrenal hyperplasia, computed
      tomography revealed an ipsilateral mass in only six and a contralateral lesion in
      one. Fourteen patients underwent unilateral adrenalectomy, which cured the
      hypertension in seven and improved it in the remainder. In patients with
      bilateral primary aldosteronism, hypertension responded to spironolactone (12.5
      50 mg/day) or amiloride (2.5-10 mg/day). CONCLUSION: When performed with careful
      regard to confounding factors, measurement of the aldosterone : renin ratio in
      all hypertensive individuals, followed by fludrocortisone suppression testing to
      confirm or exclude primary aldosteronism and adrenal venous sampling to determine
      the subtype, can result in the detection of significant numbers of patients with
      specifically treatable or potentially curable hypertension.

PMID- 14597860
TI  - Orlistat in hypertensive overweight/obese patients: results of a randomized
      clinical trial.
AB  - OBJECTIVE: To assess the effect of orlistat plus diet compared with diet alone in
      promoting weight loss and blood pressure reduction in hypertensive,
      overweight/obese patients. DESIGN: A pragmatic randomized, controlled trial.
      SETTING: Hypertension clinic of a university hospital. PATIENTS: Hypertensive
      patients aged 18-75 years with a body mass index greater than 25 kg/m(2).
      INTERVENTIONS: Orlistat 360 mg/day combined with a hypocaloric diet (treatment
      group), or a calorie-restricted diet alone (control group). MAIN OUTCOME
      MEASURES: Primary outcomes were reductions in weight and blood pressure.
      Secondary outcomes were decreases in lipid and glucose concentrations. A subgroup
      analysis of the main outcomes among diabetic and non-diabetic patients was also
      performed. RESULTS: A total of 204 patients were included in the intention-to
      treat analysis. After 12 weeks the orlistat group lost, on average, 3.7 kg and
      the control group lost 2.0 kg in weight (P < 0.001). Systolic (SBP) and diastolic
      (DBP) blood pressures decreased by 15.3 and 11.4 mmHg, respectively, in the group
      given orlistat plus a hypocaloric diet and by 11.6 and 5.2 mmHg, respectively, in
      the control group given the calorie-restricted diet alone (P = 0.25 and P =
      0.0004, respectively). Fasting glucose (0.82 and 0.17 mmol/l, P = 0.01) and total
      cholesterol (0.85 and 0.56 mmol/l, P = 0.05) were reduced to a greater extent
      with orlistat than with diet alone. The mean reduction in triglycerides with
      orlistat plus the hypocaloric diet was 0.75 mmol/l and that in the control group
      was 0.30 mmol/l (P = 0.28); the increases in high-density lipoprotein cholesterol
      were 0.05 and 0.00 mmol/l, respectively, in the two groups (P = 0.17). Treatment
      improved blood pressure and glucose control in the individuals with diabetes, but
      not in those without diabetes. CONCLUSION: In both groups there was a reduction
      in weight, blood pressure and metabolic parameters. The orlistat group performed
      better in reducing weight, DBP, glucose and cholesterol. Results show that even a
      small reduction in weight helps to control blood pressure and glucose. The cost
      benefit of the use of orlistat should be evaluated for hypertensive obese
      patients.

PMID- 14597861
TI  - Association between 24-h blood pressure monitoring variables and brain oedema in
      patients with hyperacute stroke.
AB  - OBJECTIVE: To assess the effects of blood pressure (BP) values on oedema
      formation following hyperacute stroke. DESIGN: Prospective observational study.
      SETTING AND PATIENTS: Acute stroke-unit in University hospital. A total of 240
      consecutive first-ever ischaemic or haemorrhagic stroke patients were recruited
      within 3 h of ictus. METHODS Casual and 24-h BP values were measured. Known
      stroke risk factors and clinical findings on admission were documented. Patients
      were imaged with computed tomography (CT) scan within 24 h from stroke onset and
      5 days later in order to determine the presence of brain oedema. Patients who
      received antihypertensive medication during the BP monitoring were excluded.
      RESULTS: The main outcome measure was brain oedema formation, which was present
      in 78 (32.5%) patients. The 24-h systolic (SBP), diastolic (DBP) and mean BP
      values, 24-h pulse pressure and heart rate values were significantly higher in
      patients with brain oedema than in the reference group (stroke patients without
      brain swelling). On multiple variable analysis, containing clinical, demographic
      and BP monitoring variables, 24-h SBP remained significantly (P = 0.019)
      associated with brain oedema. The odds ratio for oedema formation associated with
      each 10-mmHg increase in 24 h SBP was 1.25 (95% confidence intervals: 1.04-1.51).
      During the first 27 h after onset SBP course showed a spontaneous decline in the
      reference group, which was not documented in patients with brain oedema.
      CONCLUSION: Elevated 24-h SBP values in the acute stroke period are associated
      with subsequent brain oedema formation.

PMID- 14597862
TI  - Chronic pretreatment with candesartan improves recovery from focal cerebral
      ischaemia in rats.
AB  - OBJECTIVE: In the present study, we investigated whether systemic pretreatment
      with the AT1 receptor antagonist, candesartan, reduces neuronal injury after
      cerebral ischaemia in rats. DESIGN AND METHODS: Focal cerebral ischaemia in male,
      normotensive Wistar rats was induced by 90 min middle cerebral artery occlusion
      (MCAO) followed by reperfusion. Experiment 1: Candesartan was injected
      intravenously (i.v.) at doses of 0.1 or 0.3 mg/kg, 4 h prior to ischaemic injury.
      Experiment 2: Rats were treated with candesartan [0.1 mg/kg, subcutaneously
      (s.c.) twice daily], on 5 consecutive days prior to ischaemia. The last injection
      was administered 12 h before MCAO. Mean arterial pressure (MAP) was measured
      before, during and after ischaemic injury. Twenty-four hours after ischaemia,
      neurological outcome, infarct volume and brain oedema were evaluated. RESULTS:
      Acute i.v. pretreatment with candesartan, 0.1 and 0.3 mg/kg, dose-dependently
      decreased MAP before, during and after ischaemic injury but did not improve
      recovery from brain ischaemia. Systemic long-term s.c. pretreatment with 0.1
      mg/kg candesartan, reduced MAP during and after ischaemia to the same extent as
      did the i.v. dose of 0.1 mg administered 4 h before MCAO, but significantly
      improved neurological outcome and reduced infarction size and oedema of the
      ipsilateral hemisphere when compared with the vehicle-treated group. CONCLUSION:
      Long-term blockade of AT1 receptors improves neurological outcome of focal
      cerebral ischaemia and protects brain tissue against ischaemic injury.

PMID- 14597863
TI  - Coronary flow reserve in hypertensive patients with appropriate or inappropriate
      left ventricular mass.
AB  - OBJECTIVE: To assess the association between coronary flow reserve (CFR) and
      levels of left ventricular mass (LVM) exceeding the compensatory needs in
      arterial hypertension. DESIGN, SETTINGS AND PATIENTS: The association between the
      excess of LV mass and CFR was assessed in a population of 40 consecutive
      hypertensive outpatients free of coronary heart disease, 22 with appropriate and
      17 with inappropriately high LVM (i.e. LVM exceeding 128% of the value predicted
      by sex, stroke work and height in m(2.7)). The CFR (the ratio between
      dipyridamole and basal diastolic peak velocity) of the distal left anterior
      descending artery was measured by transthoracic Doppler echocardiography.
      RESULTS: Patients with inappropriate LVM had similar age, body mass index (BMI),
      baseline blood pressure (BP) and coronary velocities, but lower LV systolic
      function, post-dipyridamole diastolic peak velocities (P < 0.05) and lower CFR (P
      < 0.002) than patients with appropriate LVM. CFR was negatively related to the
      extent of the excess of LVM (beta = -0.44, P < 0.005), independently of potential
      combined effect of age, BMI and post-dipyridamole diastolic BP. Impairment of CFR
      (i.e. < 2) was better discriminated by identification of clear-cut inappropriate
      LVM (P < 0.004) than by the presence of LV hypertrophy (i.e. LV mass index > or =
      51 g/m(2.7); P = 0.057). CONCLUSIONS: In hypertensive patients free of coronary
      artery disease, the degree of reduction in CFR is associated with the excess of
      LVM beyond the values compensatory for individual haemodynamic load. This
      relation is also independent of the presence of LV hypertrophy.

PMID- 14597864
TI  - Diagnostic value of exercise electrocardiography and dipyridamole stress
      echocardiography in hypertensive and normotensive chest pain patients with right
      bundle branch block.
AB  - OBJECTIVES: Studies on the diagnostic value of exercise electrocardiography in
      right bundle branch block produced controversial results, and data on the
      accuracy of stress echo are still lacking. The aim of the study was to compare
      the diagnostic value of exercise electrocardiography and dipyridamole stress echo
      in chest pain patients with right bundle branch block, and to verify whether
      stress testing accuracy is affected by history of hypertension. METHODS: The
      study group was made up of 71 patients (56 men, aged 63 +/- 8 years) with chest
      pain of unknown origin and complete right bundle branch block. Of them, 35 were
      hypertensives and 36 normotensives. Patients performed, on different days and in
      random order, exercise electrocardiography and dipyridamole stress echo and
      underwent coronary angiography. RESULTS: Significant (> or = 70% diameter
      stenosis) coronary artery disease was found in 34 patients (17 hypertensives and
      17 normotensives). Positive exercise electrocardiography (ST-segment shift > 1 mm
      at 80 ms after the J point in leads V5 and V6 or leads II and Vf) and
      dipyridamole stress echo (new wall motion abnormalities) were observed in 38 and
      30 patients, respectively. The result of tests was concordant in 69% of
      hypertensives and 92% of normotensives. The two tests shared the same sensitivity
      in hypertensives (82%) and normotensives (71%). Of 37 patients without coronary
      artery disease, 12 had a false-positive result during exercise
      electrocardiography and four during stress echo. The specificity was lower for
      exercise electrocardiography than for stress echo in hypertensives (50 versus
      89%, P = 0.0006), while no difference was evidenced in normotensives (84 versus
      89%, P = 0.4). In hypertensives, the accuracy, positive, and negative predictive
      values were 66, 61, and 75% for exercise electrocardiography, and 86, 87, and 84%
      for stress echo. Corresponding figures in normotensives were 78, 80, and 76% for
      exercise electrocardiography, and 81, 86, and 77% for stress echo. CONCLUSIONS:
      In chest-pain patients with right bundle branch block, dipyridamole stress echo
      was effective to diagnose coronary artery disease in both normotensives and
      hypertensives. Moreover, it exhibited superior diagnostic information than
      exercise electrocardiography in hypertensives, due to significantly higher
      specificity. However, the two tests had similar diagnostic value in
      normotensives.

PMID- 14597865
TI  - Combined antihypertensive therapy improves moderate heart failure.

PMID- 14597866
TI  - Use of arterial transfer function for the derivation of aortic waveform
      characteristics.

PMID- 14597868
TI  - Applicability and benefit of arterial transfer functions.

PMID- 14597870
TI  - Doxycycline and other tetracyclines in the treatment of bone metastasis.
AB  - The tetracycline family includes tetracycline, doxycycline and minocycline, all
      of which have been used as antibiotics effectively for decades. New uses emerged
      for these compounds after their effect on mitochondrial function was discovered.
      Cytostatic and cytotoxic activity of these compounds was shown against cell lines
      of various tumor origins. In addition, tetracyclines and chemically modified
      tetracyclines inhibit the activity of several matrix metalloproteinases (MMPs).
      Given the importance of these enzymes in tumor cell invasion and metastatic
      ability, the potential use of tetracyclines in cancer therapy needed to be
      investigated. Col-3, a chemically modified tetracycline, is now the subject of
      clinical trials in cancer patients. However, the potential of tetracyclines in
      cancer therapy takes on an added dimension in the bone. MMPs have been shown to
      be important mediators of metastasis formation in the bone, contributing largely
      to the morbidity of breast cancer and prostate cancer patients. The natural
      osteotropism of tetracyclines would allow them to be highly effective in the
      inhibition of MMPs produced by osteoclasts or tumor cells in the bone. This
      hypothesis has now been confirmed by experimental evidence showing that
      doxycycline reduces tumor burden in a mouse model of breast cancer-derived
      osteolytic bone metastasis. This effect is likely due to a combination of
      multiple roles of doxycycline, including MMP inhibition and a negative effect on
      osteoclast differentiation and survival. These encouraging results have now paved
      the way for an ongoing trial of doxycycline in early combination therapy for
      breast cancer and prostate cancer patients.

PMID- 14597871
TI  - Capecitabine monotherapy and in combination with immunotherapy in the treatment
      of metastatic renal cell carcinoma.
AB  - This prospective trial aimed to evaluate the therapeutic effects and systemic
      toxicities of capecitabine monotherapy and capecitabine treatment combined with
      biological response modifiers in patients with metastatic renal cell carcinoma.
      Fifty-four patients suffering from metastatic renal cell carcinoma progressing
      under first-, second- or third-line treatment entered the trial. Capecitabine was
      given orally at a dose of 2500 mg/m2 daily divided into two doses for 14 days,
      followed by a 7-day rest in the monotherapy as well as in the combination
      treatment. This schedule was repeated in 3-week cycles. The combination therapy
      consisted of capecitabine and an immunotherapy treatment, which consisted either
      of interferon (IFN)-gamma1b (100 mg/day) administered consecutively 5 times
      weekly during weeks 1 and 2, and recombinant interleukin (IL)-2 (4.5 MU/day)
      administered on 4 consecutive days during weeks 3 and 4, every 6 weeks, or IFN
      alpha (6 MioIE/day) administered 3 times a week. Fifty-two patients are now
      evaluable for response and 54 patients for toxicity. We observed a partial
      response to treatment in five patients (9.6%), minor response in five patients
      (9.6%), stable disease in 32 patients (61.6%) and only 10 patients (19.2%) showed
      continued disease progression despite treatment. Outpatient capecitabine was well
      tolerated. We did not observe any WHO grade IV toxicities. We conclude that
      capecitabine monotherapy and capecitabine treatment in combination with
      biological response modifiers appear to be effective regimens with favorable
      toxicity profiles in patients with advanced renal cell carcinoma. Capecitabine
      monotherapy seems to be superior than the combination treatment because of its
      easier application form.

PMID- 14597872
TI  - Comparative neurotoxicity of weekly non-break paclitaxel infusions over 1 versus
      3 h.
AB  - We evaluated the effects of weekly short infusions of paclitaxel (PAC) on the
      development of a peripheral neuropathy (PNP) as primary endpoint. Patients with
      advanced cancer were randomized to a weekly regimen of PAC (100 mg/m2) infused
      over 1 versus 3 h. PNP was evaluated by a clinical score including sensory
      symptoms, strength, tendon reflexes and vibratory sense (range 0-12; PNP >3
      points). Kaplan-Meier-type curves were calculated. In total, 22 study centers
      enrolled 121 patients, 92 assessable for analysis. The probability to exceed a
      PNP score of 3 increased from 0.20 versus 0.30 after six to 0.68 versus 0.47
      after 12 administrations (1 versus 3 h: p = 0.66). After 12 weeks of therapy only
      a quarter of assessable patients were free of PNP. Cox analysis yielded a
      relative risk of 1.10 for 1-h infusions (p = 0.80). We observed a rapid
      increasing risk of PNP manifestation in the course of weekly PAC administrations
      without significant differences between 1- and 3-h infusions. This is in contrast
      to pharmacokinetic observations indicating that a shortening of infusion time
      might enhance neurotoxicity by increasing the AUC of Cremophor. A majority of
      patients experiencing neurotoxic effects require the investigation of potential
      nerve protectors in future clinical trials accompanying PAC therapy.

PMID- 14597873
TI  - Liposomal daunorubicin (DaunoXome) in multiple myeloma: a modified VAD regimen
      using short-term infusion.
AB  - Liposomal daunorubicin replacing conventional anthracyclines may reduce toxicity
      and enhance efficacy of chemotherapy. In this phase I study, we evaluated
      liposomal daunorubicin (DaunoXome) in combination with vincristine and
      dexamethasone for toxicity, pharmacokinetics and potential efficacy in patients
      with multiple myeloma. The main objective was to determine the maximum tolerated
      dose (MTD) and dose-limiting toxicity (DLT) of liposomal daunorubicin combined
      with vincristine and dexamethasone (VLDD). Additionally, pharmacokinetics were
      determined at higher dose levels. Seventeen multiple myeloma patients were
      enrolled in this trial; 76% of the patients had relapsed or refractory multiple
      myeloma. Successive cohorts received liposomal daunorubicin at doses of 40, 60,
      80 and 100 mg/m2 on day 1 in combination with vincristine 1.4 mg/m2 (day 1) and
      oral dexamethasone (40 mg, days 1-4). DLT occurred at 100 mg/m2. Liposomal
      daunorubicin at 80 mg/m2 was well tolerated in this protocol and should be used
      for further phase II studies with the VLDD regimen. In this phase I trial, 64% of
      the patients achieved a partial remission or a minor response.

PMID- 14597874
TI  - Induction chemotherapy with docetaxel, cisplatin, fluorouracil and l-leucovorin
      for locally advanced head and neck cancers: a modified regimen for Japanese
      patients.
AB  - Combination chemotherapy with docetaxel (T), cisplatin (P), fluorouracil (5-FU)
      and leucovorin has been reported to have major activity against squamous cell
      carcinoma of the head and neck (SCCHN) administered as a 4-day (TPFL4) or 5-day
      (TPFL5) regimen. The purpose of this study was to evaluate the efficacy and
      toxicity of a modified TPFL regimen (m-TPFL) for locally advanced SCCHN,
      consisting of a modified dosage with docetaxel, cisplatin, 5-FU and l-leucovorin
      (l-LV) designed for Japanese patients. Organ preservation of the primary tumor
      site was also assessed. Thirty-four Japanese patients with locally advanced SCCHN
      were eligible. Docetaxel was administered as a 1-h i.v. infusion at 48 mg/m2 on
      day 1; cisplatin, 24 mg/m2/day; 5-FU, 560 mg/m2/day and l-LV, 125 mg/body/day
      were delivered on days 1-4 by continuous i.v. infusion. This regimen was
      administered every 28 days. Patients who achieved a complete response (CR) after
      induction chemotherapy underwent radiation therapy alone. Ninety-one cycles were
      administered. The main hematological toxicity was neutropenia, classified as
      grade III or IV in 18.7% of cycles. The most common non-hematologic toxicities
      included anorexia, stomatitis and alopecia. The clinical overall response rate to
      m-TPFL was 88.2%, with 58.8% CRs and 29.4% partial responses. After definitive
      locoregional therapy, 25 of 34 patients were disease-free with preserved primary
      tumor site anatomy. Overall and progression-free survival rates at the 2-year
      follow-up are 92.8 and 75.3%, respectively. Our m-TPFL regimen designed for
      Japanese patients yielded excellent response rates with an acceptable toxicity
      profile in good-performance-status patients.

PMID- 14597875
TI  - Semi-extended, six weekly rituximab infusions in pre-treated advanced low-grade B
      cell non-Hodgkin's lymphoma: a phase II study.
AB  - Either four or eight weekly rituximab infusions in relapsed or refractory low
      grade or follicular B cell non-Hodgkin's lymphoma (NHL) are well tolerated and
      efficacious. This phase II trial investigated the safety and efficacy of six
      weekly rituximab doses in chemotherapeutically pre-treated relapsed or refractory
      low-grade NHL patients. Sixty-eight patients (median age 64 years) received six
      i.v. rituximab infusions 375 mg/m2 weekly. All patients had received one or more
      prior therapies (median 2; range 1-18). Forty-two patients had progressive
      disease and were evaluated for toxicity and efficacy; 12 of these required re
      treatment with six weekly rituximab infusions. Twenty-six patients received
      rituximab as remission consolidation therapy and were assessed for toxicity only.
      No patients discontinued because of adverse events. Most adverse events were
      National Cancer Institute grade 1 (2-9%) or 2 (3-5%) and usually occurred during
      the first infusion. No hematological abnormalities were observed. Overall
      response rate was 59% (median time to response 2 weeks) and 10 of 12 re-treated
      patients responded. Median time to progression for all patients was 14 months and
      for responders 21 months. More than half the 42 patients evaluated for efficacy
      and more than 70% of the 25 responding patients still survived longer than 3
      years after treatment. The safety profile and efficacy achieved in this study
      compare favorably with those seen with four or eight weekly doses in pre-treated
      low-grade NHL.

PMID- 14597876
TI  - Population pharmacokinetics of oxaliplatin in patients with metastatic cancer.
AB  - Our aim was to develop a population pharmacokinetic model of ultrafilterable
      oxaliplatin in metastatic cancer patients. Oxaliplatin was administered by 2- or
      4-h infusions, 50, 65, 75, 85, 100 or 130 mg/m2 to 56 patients. Blood samples
      were collected over 28 h. Plasma concentrations of ultrafilterable oxaliplatin
      were determined by flameless atomic absorption spectrophotometry. Population
      pharmacokinetic analysis was performed using a non-linear mixed-effects modeling
      method. Ultrafilterable oxaliplatin concentration-time profiles showed a
      secondary peak or a shoulder aspect post-infusion, attributed to the existence of
      an enterohepatic recirculation (EHR). They were best described by a two
      compartment model incorporating an EHR component. Plasma clearance (CL) was
      related positively to body weight (BW) and negatively to serum creatinine (SCr),
      and was greater in male patients than in female patients. This covariate modeling
      resulted in a decrease in the interindividual variability for CL from 104 to 62%.
      The central distribution volume (V1) and inter-compartmental clearance (Q) were
      related to BW. Typical population estimates of CL, central distribution volume
      (V1), input rate constant into gallbladder (k1B) and lag time for drug
      reabsorption (TLAG) were 14.1 or 8.5 l/h (male or female patients), 24.9 l, 1.8 h
      1 and 2.0 h, respectively. The final pharmacokinetic model was validated using
      200 bootstrap samples of the original data. We conclude that a two-compartment
      with EHR model adequately described ultrafilterable oxaliplatin pharmacokinetics,
      explaining a secondary transient increase in concentration. This study identified
      combined-covariate-effects ultrafilterable oxaliplatin clearance, supporting dose
      adjustment of oxaliplatin based on BW, gender and corrected for SCr level, if
      drug exposure is thought to be related to therapeutic or toxic issues.

PMID- 14597877
TI  - Combined effect of topical arsenic trioxide and radiation therapy on skin
      infiltrating lesions of breast cancer-a pilot study.
AB  - It has been reported that arsenic trioxide (As2O3) is an apoptosis inducer and
      radiation sensitizer for various cancer cell lines. In this study of breast
      cancer patients, we examined the combined effect of topical As2O3 and radiation
      therapy on fungating and/or skin-infiltrating lesions of breast cancer. The
      dermatological, gastrointestinal, hematological, renal and hepatic toxicities of
      the treatment were also monitored. As2O3 gel (0.05%) was applied to tumor lesions
      1 h prior to delivery of each fraction, with the gel removed about 5 min before
      the irradiation. Superficial radiation was delivered using an electron beam from
      a linear accelerator. Every week, the tumor lesions were photographed to evaluate
      effectiveness, and blood was sampled to monitor changes in hemogram and
      biochemical profile. Seven breast cancer patients with cutaneous metastasis were
      enrolled in this study. In terms of tumor, the rates for complete, partial
      response and stable disease were 42.9 (three of seven), 42.9 (three of seven) and
      14.3% (one of seven), respectively. The skin pain, assessed by a visual analog
      scale, and secretion from all of the seven superficial and fungating wounds
      decreased markedly after treatment. Significant bone marrow suppression or
      granulocytosis was not noted. Further, changes in renal and hepatic function were
      also not significant. It seems reasonable to conclude that As2O3 may be an
      effective and safe radiosensitizer for palliative radiotherapy for skin
      infiltrating lesions of breast cancer.

PMID- 14597878
TI  - Thrombotic microangiopathy and digital necrosis: two unrecognized toxicities of
      gemcitabine.
AB  - We report one new case of hemolytic-uremic syndrome (HUS) and one case of digital
      necrosis after treatment with gemcitabine (Gemzar). Case 1, a 34-year-old man,
      was given first-line metastatic treatment with gemcitabine for a adenocarcinoma
      of the pancreas. After a cumulative dose of 10 000 mg/m2 gemcitabine, the onset
      of subacute renal failure associated with hemolytic anemia of mechanical origin
      was observed. A diagnosis of probable gemcitabine-induced thrombotic
      microangiopathy was arrived at. Symptoms resolved after stopping the
      chemotherapy, in spite of the progression of the disease. Case 2, a 61-year-old
      man, was administered a combination of gemcitabine and a platinum salt as first
      line metastatic treatment for carcinoma of the bladder urothelium. Following a
      cumulative dose of 10 000 mg/m2 of gemcitabine, the patient suffered from
      bilateral peripheral vascular disease of somewhat acute onset with hemorrhagic
      lesions of the finger pads that became necrotic. The work-up was negative and a
      causal relationship was attributed to gemcitabine. The patient made good progress
      when given an i.v. infusion of Ilomedine (iloprost trometamol) and chemotherapy
      was withdrawn. We conclude that gemcitabine must be added to the list of drugs
      that cause HUS and necrotizing vasculitis.

PMID- 14597880
TI  - beta-Lapachone-induced apoptosis is associated with activation of caspase-3 and
      inactivation of NF-kappaB in human colon cancer HCT-116 cells.
AB  - beta-Lapachone is a naturally occurring quinone obtained from the bark of the
      lapacho tree (Tabebuia avellanedae) with cancer chemopreventive properties. The
      objective of the present study was to investigate the effect of beta-lapachone on
      the cell growth and apoptosis in human colon carcinoma tumor cell line HCT-116.
      Exposure of HCT-116 cells to beta-lapachone resulted in growth inhibition and
      induction of apoptosis in a dose-dependent manner as measured by hemocytometer
      counts, fluorescence microscopy and flow cytometric analysis. This increase in
      apoptosis was associated with a decrease in Bcl-2 protein expression, an increase
      in caspase-3 activity, a decrease in intact poly(ADP-ribose) polymerase protein
      levels and degradation of beta-catenin. After beta-lapachone treatment, the
      nuclear protein levels of NF-kappaB and the activity of NF-kappaB-DNA binding
      were markedly decreased. beta-Lapachone treatment also resulted in inhibition of
      the transcriptional activity of NF-kappaB-luciferase reporter plasmid suggesting
      that beta-lapachone-induced apoptosis may be partly regulated through the
      inactivation of NF-kappaB.

PMID- 14597879
TI  - Drug- and cell-mediated antitumor cytotoxicities modulate cross-presentation of
      tumor antigens by myeloid dendritic cells.
AB  - The way a tumor cell dies is believed to influence both its engulfment by
      dendritic cells (DC) and access of the relevant antigen(s) to the cross
      presentation pathway. Here we have studied the effect of lymphokine activated
      killer (LAK) cells, gamma-radiation and the antimetabolite drug 5-fluorouracil (5
      FU) on tumor uptake by HLA-matched DC, and DC presentation of tumor antigens to
      autologous T lymphocytes. LAK cells and radiation were the best inducers of
      apoptotic death (Annexin-V+/propidium iodide-) on the gastric cell line KATO III
      and a primary gastric carcinoma, respectively. The highest rate of tumor uptake
      by monocyte-derived, granulocyte macrophage colony stimulating factor/interleukin
      (IL)-4-driven DC was associated with 5-FU, followed by radiation. These
      treatments also induced high levels of heat shock protein (hsp70). In contrast,
      only DC that had been taken up 5-FU- or LAK-treated tumors up-modulated IL-12 and
      presented tumor-associated antigens with increased efficiency, as shown by class
      I MHC-restricted interferon-gamma release and cytotoxic responses by autologous
      lymphocytes. Together, these data indicate that apoptotic death induced by anti
      cancer therapies can induce distinct patterns of class I MHC cross-presentation
      of gastric carcinoma-associated antigens to cytotoxic T lymphocyte precursors.

PMID- 14597881
TI  - Medical treatment of peripheral arterial disease.
AB  - PURPOSE OF REVIEW: The evolution of interventional treatments of peripheral
      arterial disease is progressing at a dizzying pace. However, optimized medical
      therapy of these patients may be neglected. Recent advances in our understanding
      of atherosclerosis and the epidemiology of vascular disease reemphasize the
      importance of a consistent and complete medical regimen. They have also opened
      new avenues for potential therapy. RECENT FINDINGS: A diagnosis of peripheral
      arterial disease confers an increased risk of morbidity and mortality that can be
      at least partially mitigated with a properly designed medical regimen. New
      evidence supports the importance of risk factor modification including
      controlling hypertension, lowering lipid levels, and the routine use of
      antiplatelet agents. For claudication symptoms, several newer drugs and the use
      of immune-modifying therapy are showing some improvement in symptoms. The use of
      gene therapy and other means to achieve improved collateral formation in ischemic
      tissues are showing some promise in the early stages of study. SUMMARY:
      Peripheral arterial disease is a marker of cardiovascular morbidity and mortality
      risk. An individualized plan should be devised to include smoking cessation,
      exercise, lowering serum lipids, lowering high blood pressure, and daily
      antiplatelet therapy. Supervised exercise programs and cilostazol remain the
      first-line medical therapies for claudication symptoms, and anticoagulants are
      added to patients who have bypasses at high risk for thrombosis. The utilities of
      immune-modifying, antibiotic, and angiogenic therapies remain to be proven.

PMID- 14597882
TI  - Penetrating atherosclerotic ulcer of the aorta: treatment by endovascular stent
      graft placement.
AB  - PURPOSE OF THE REVIEW: To summarize the current clinical experience with
      endovascular stent-graft repair in patients presenting with penetrating
      atherosclerotic ulcer of the descending thoracic aorta. RECENT FINDINGS:
      Penetrating atherosclerotic ulcer is increasingly acknowledged as a pathologic
      variant of classic false lumen aortic dissection with a high incidence of
      bleeding complications and rupture in up to 40% of patients. So far, no generally
      accepted therapeutic regimen has been established, as the natural history of
      penetrating atherosclerotic ulcer is not yet fully understood. Recently, however,
      penetrating atherosclerotic ulcer is increasingly considered to be treated more
      aggressively (preferentially surgically). Given the high morbidity and mortality
      of aortic surgery, endovascular stent-graft repair may be an attractive, less
      invasive alternative in selected patients with penetrating atherosclerotic ulcer.
      Sealing of a penetrating ulcer by the stent-graft reduces wall stress and thus
      provides stabilization of the diseased aortic segment. SUMMARY: To date, there is
      limited experience with endovascular repair in penetrating atherosclerotic ulcer,
      suggesting that endovascular stent-graft repair is safe and effective. Long-term
      results are, however, required to fully establish the efficacy of endovascular
      repair in penetrating atherosclerotic ulcer.

PMID- 14597883
TI  - Evaluation and medical treatment of peripheral arterial disease.
AB  - PURPOSE OF REVIEW: This review reports various advances in the evaluation and
      medical management of patients with peripheral arterial disease (PAD) in the last
      1 to 2 years. RECENT FINDINGS: Several community surveys have clearly highlighted
      the fact that despite being a very highly prevalent disease, physicians
      underdiagnose and undertreat PAD. This led to the Executive Committee of the
      Prevention of Atherothrombotic Disease Network to issue a "call to action,"
      citing critical issues in PAD detection and management. SUMMARY: PAD affects more
      than 27 million people in North America and Europe, and the prevalence of this
      disease continues to increase as the population ages. This disease has
      significant adverse effects on the quality of life and survival, with mortality
      as high as 30% in 5 years and 50% in 10 years. Although surgical, endovascular,
      and medical therapies for atherosclerosis in general, and PAD specifically,
      continue to be developed, there appears to be considerable room for improvement
      in physician adoption of proven effective therapies, such as cholesterol-lowering
      therapies and blood pressure management. Additionally, new therapies, such as
      gene transfer and cell therapy, are under development for this population.

PMID- 14597884
TI  - Endoscopic vein harvesting in cardiac surgery.
AB  - PURPOSE OF REVIEW: Endoscopic vein harvesting (EVH) is a relatively new
      technique, developed to help minimize morbidities associated with traditional
      harvesting techniques. Wound dehiscence, recurrent cellulitis, hematomas,
      neuropathies, and impaired mobility are often experienced by patients who have
      undergone open harvest techniques. RECENT FINDINGS: Use of this developing
      technique has been hindered due to the skill required to perform this task and
      time constraints that are often encountered in the operating room. SUMMARY:
      However, an adequate vein segment can be obtained in a timely fashion, and
      harvest site infections are reduced when this method is employed. Results thus
      far have revealed a decreased infection rate, fewer observed morbidities, and
      overall patient satisfaction.

PMID- 14597885
TI  - Treatment of combined coronary and carotid artery disease.
AB  - PURPOSE OF REVIEW: The purpose of this review is to evaluate the current
      indications and results of treatment of combined coronary and carotid disease.
      Synchronous carotid stenosis in patients with coronary artery disease poses a
      management challenge in patients with advanced atherosclerosis. RECENT FINDINGS:
      Recent case series continue to demonstrate concomitant coronary and carotid
      disease with significant carotid stenosis greater than 70% in approximately 8% of
      patients evaluated for coronary artery bypass grafting. Surgical management
      options include staged operations addressing the carotid stenosis first, reverse
      staged operations addressing the coronary disease first, and combined synchronous
      operations addressing both territories during the same anesthetic. Recent reports
      demonstrate safety and acceptable risks with each operative approach. Lower
      trends in stroke rates were noted following staged procedures when compared with
      combined procedures. However, several metaanalyses showed no significant
      difference in rates of combined morbidity and mortality for all three strategies.
      Total morbidity and mortality risks for combined disease tended to be higher than
      for isolated coronary artery bypass grafting or carotid endarterectomy procedures
      performed for disease in a single vascular territory. SUMMARY: Despite a large
      volume of data present in the literature, the treatment indications and surgical
      options remain controversial. We currently advocate treatment of symptomatic
      territory first in favor of staged procedures and reserve combined procedures for
      patients with critical stenosis or symptoms in both territories.

PMID- 14597886
TI  - Revascularization and ventricular restoration in patients with ischemic heart
      failure: the STICH trial.
AB  - PURPOSE OF REVIEW: As techniques for the management of patients with ischemic
      heart failure have evolved, controversy has arisen with respect to the roles of
      revascularization and ventricular restoration procedures. This review addresses
      current thinking on the management of these patients and describes a prospective
      randomized trial that will have an impact on future treatment selection. RECENT
      FINDINGS: Although the basis for improved survival with coronary artery bypass
      grafting lies in the viability of ischemic myocardium, nuclear medicine studies
      and stress echocardiography have failed to adequately select for tissues that are
      capable of recovery. Recent studies have suggested an additional benefit to
      combining ventricular restoration with bypass surgery. However, the role for
      these techniques has not been definitively established. SUMMARY: The currently
      enrolling Surgical Treatment for Ischemic Heart Failure (STICH) trial promises to
      address these issues and thereby improve the management of patients with this
      disease.

PMID- 14597887
TI  - Prediction of sites of coronary atherosclerosis progression: In vivo profiling of
      endothelial shear stress, lumen, and outer vessel wall characteristics to predict
      vascular behavior.
AB  - PURPOSE OF REVIEW: Native atherosclerosis and in-stent restenosis are focal and
      evolve independently. The endothelium regulates arterial behavior by responding
      to its local environment of hemodynamic stresses, in particular, shear stress.
      Identification of endothelial shear stress and arterial wall characteristics may
      allow for the prediction of the progression of atherosclerosis. Accurate
      identification of arterial segments at high risk for progression may permit
      preemptive intervention strategies to avoid adverse coronary events. RECENT
      FINDINGS: In vitro studies indicate that low endothelial shear stress upregulates
      the genetic and molecular responses leading to the initiation and progression of
      atherosclerosis, and promotes inflammation and formation of other features
      characteristic of vulnerable plaque. Physiologic endothelial shear stress is
      vasculoprotective and fosters quiescence of the endothelium and vascular wall.
      High endothelial shear stress promotes platelet aggregation. Recent studies have
      now provided evidence that endothelial shear stress and vascular wall morphology
      along the course of human coronary arteries can be characterized in vivo, and, in
      serial studies, may actually predict the focal areas in which atherosclerosis
      progression occurs. SUMMARY: Rapidly evolving methodologies are able to
      characterize the arterial wall and the local hemodynamic environmental factors
      likely responsible for progression of coronary disease in humans. These new
      diagnostic modalities allow for identification of plaque progression. Future
      studies need to identify the factors responsible for vulnerable plaque formation.
      The current availability of drug-eluting stents with a low risk of restenosis
      allows for consideration of preemptive intervention strategies for these high
      risk vascular sites such that future adverse coronary events can be averted.

PMID- 14597888
TI  - Clinical use of high sensitivity C-reactive protein for the prediction of adverse
      cardiovascular events.
AB  - PURPOSE OF REVIEW: Inflammation plays a central role in the initiation,
      progression, and destabilization of vascular atheroma. In an attempt to improve
      global cardiovascular risk assessment, considerable research has focused on
      markers of inflammation; in particular, high-sensitivity C-reactive protein, a
      pentraxin innate immune recognition molecule and classic acute-phase reactant.
      RECENT FINDINGS: Multiple prospective studies now demonstrate that high
      sensitivity C-reactive protein is a potent predictor of future cardiovascular
      events at all levels of low-density lipoprotein cholesterol, all levels of the
      Framingham Risk Score, and all levels of severity of the metabolic syndrome.
      Moreover, high-sensitivity C-reactive protein appears to be implicated in acute
      coronary syndromes and provides prognostic information on vascular risk among
      patients with renal dysfunction. In clinical settings, high-sensitivity C
      reactive protein levels more than 3 mg/L are associated with the highest vascular
      risk. SUMMARY: High-sensitivity C-reactive protein evaluation has recently been
      endorsed by the Centers for Disease Control and Prevention and by the American
      Heart Association to be used in conjunction with lipid evaluation as part of
      global risk prediction. Emerging evidence further suggests that high-sensitivity
      C-reactive protein can be used to target pharmacologic and lifestyle
      interventions designed to prevent first as well as recurrent cardiovascular
      events.

PMID- 14597889
TI  - Peroxisome proliferator activated receptor gamma and its activation in the
      treatment of insulin resistance and atherosclerosis: issues and opportunities.
AB  - Atherosclerosis remains a major complication of type 2 diabetes mellitus.
      Increasing data suggest insulin resistance, and its associated metabolic
      abnormalities, may underlie many of the cardiovascular complications seen among
      patients with insulin resistance and/or diabetes mellitus. This insight has also
      suggested that therapeutic approaches targeting insulin resistance may not only
      improve metabolism but also limit complications like atherosclerosis and the
      inflammation that contributes to it. Thiazolidinediones, agonists of the nuclear
      receptor peroxisome proliferator activated receptor gamma, are one such insulin
      sensitizing therapeutic intervention in current use among patients with type 2
      diabetes mellitus. The existing data regarding thiazolidinedione effects on the
      cardiovascular system are reviewed and considered, along with the future
      prospects for this emerging drug class.

PMID- 14597890
TI  - Stress echocardiography versus myocardial SPECT for risk stratification of
      patients with coronary artery disease.
AB  - PURPOSE OF REVIEW: Diagnostic testing using noninvasive imaging has become an
      integral part of risk stratification in patients with coronary artery disease. It
      is important to understand the integral strengths and weaknesses between the
      different modalities of stress testing and to apply accurately the type of test
      the clinical scenario demands. RECENT FINDINGS: There have been tremendous
      advances made in the field of cardiac imaging. Both myocardial perfusion imaging
      and stress echocardiographic techniques continue to evolve and play an important
      role in the assessment of patients with coronary artery disease. SUMMARY: In this
      review the authors discuss the relative merits of both stress echocardiography
      and myocardial single photon emission computed tomographic imaging for diagnosis
      and risk stratification of patients with coronary artery disease.

PMID- 14597891
TI  - New frontiers in risk stratification using stress myocardial perfusion single
      photon emission computed tomography.
AB  - PURPOSE OF REVIEW: The purpose of this review is to review the recent published
      literature since 2002 for studies using stress myocardial perfusion single photon
      emission computed tomography for determination of the prognostic value of
      testing. RECENT FINDINGS: A series of manuscripts dealing with myocardial
      perfusion single photon emission computed tomography have been published over the
      past 2 years that have altered a number of the most basic concepts defining risk
      stratification. These studies may have redefined the manner in which noninvasive
      stress imaging results will be interpreted and applied. SUMMARY: Recent studies
      have expanded the understanding of how stress myocardial perfusion single photon
      emission computed tomography is helpful in the identification of risk, enhanced
      the means of identifying risk, and improved its use as a means to identify
      optimal posttest treatment.

PMID- 14597892
TI  - Role of non-high-density lipoprotein cholesterol in prevention of cardiovascular
      disease: updated evidence from clinical trials.
AB  - PURPOSE OF REVIEW: Although current clinical practice and treatment guidelines
      focus on low-density lipoprotein cholesterol as the basis for diagnosing and
      treating atherogenic dyslipidemias, many persons who develop cardiovascular
      disease do not have substantially elevated low-density lipoprotein cholesterol
      levels but may have low levels of high-density lipoprotein cholesterol and
      elevated triglycerides. Assessment of non-high-density lipoprotein cholesterol
      level provides a measure of cholesterol contained in all atherogenic particles,
      including low-density lipoprotein, lipoprotein(a), and triglyceride-rich
      particles such as very low density lipoprotein, very low density lipoprotein
      remnants, and intermediate-density lipoprotein. In the third Adult Treatment
      Panel guidelines of the US National Cholesterol Education Program, non-high
      density lipoprotein cholesterol was introduced as a secondary target of therapy
      in persons with high triglyceride levels. RECENT FINDINGS: A growing number of
      epidemiological studies and clinical trials have examined the relation between
      non-high-density lipoprotein cholesterol level and cardiovascular disease events.
      Non-high-density lipoprotein cholesterol has been shown to be a better predictor
      for cardiovascular events than low-density lipoprotein cholesterol, and trials of
      statin therapy have demonstrated reductions in non-high-density lipoprotein
      cholesterol as well as low-density lipoprotein cholesterol. SUMMARY: Clinical
      trial evidence indicates the importance of incorporating all atherogenic
      lipoprotein particles in risk stratification. Non-high-density lipoprotein
      cholesterol is the most readily available surrogate marker for assessment of
      these particles and may also be a potential target of lipid-altering therapy.
      Statin therapy, which has already been demonstrated to decrease cardiovascular
      morbidity and mortality, provides significant reductions in non-high-density
      lipoprotein cholesterol.

PMID- 14597893
TI  - [Angiogenesis and tumor pathology: an interim evaluation].

PMID- 14597894
TI  - [Prognostic significance of VEGF receptors, VEGFR-1 (Flt-1) and VEGFR-2 (KDR/Flk
      1) in breast carcinoma].
AB  - OBJECTIVES: The aim of this study was to investigate the prognostic value of
      vascular endothelial growth factor (VEGF) receptors, VEGFR-1 (Flt-1) and VEGFR-2
      (KDR/Flk-1) in breast carcinoma. METHODS: VEGF receptor expression was
      investigated using immunohistochemical assays with monoclonal antibodies on
      frozen sections in a series of 918 patients and was correlated with prognostic
      parameters and with long-term follow-up (median, 11.3 years). VEGFR-1 and VEGFR-2
      immunostained surface was evaluated in percentage of the total tumor specimen
      surface by light microscopy (x100). RESULTS: VEGFR-1 and VEGFR-2 were strongly
      expressed in endothelial cells within blood microvessels, and weakly in tumor
      cells. Univariate (Kaplan Meier) analysis showed that VEGFR-1 positive tumor
      surface (cut off=5%) was not correlated with survival, but was significantly
      correlated with high metastasis risk (p=0.03) and relapse (p=0.01) in all
      patients, and in those with node negative tumors (p=0.001 and p=0.01
      respectively). In multivariate analysis (Cox model), VEGFR-1 expression was
      identified as an independent prognostic indicator. Univariate analysis showed
      that VEGFR-2 positive tumor surface (cut off=10%) was not correlated with
      survival or with metastasis risk and relapse. CONCLUSION: Our results show that
      VEGFR-1 immunohistochemical expression permits the identification of patients
      with poor outcome, particularly those with node negative tumors, with high risk
      of metastasis and relapse. VEGFR-1 immunodetection may further be considered as a
      potential tool for evaluating tumor agressiveness and therapeutic strategies in
      breast cancer.

PMID- 14597895
TI  - [Bladder tumors and molecular markers. Current status and perspectives].
AB  - With 15,000 new cases each year, bladder tumors are the second leading urological
      cancer in France, after prostate carcinoma. In spite of advances in surgical
      techniques and therapeutic protocols based on trans-urethral resection associated
      with additive treatment (immunotherapy or endovesical chemotherapy), the natural
      course of superficial bladder tumors remains marked by two risks: recurrence and
      progression. In spite of the impressive efforts developed by molecular biologists
      searching for new specific markers, none of the markers can currently replace
      histological features such as stage and grade. Although detection of
      microsatellite instability is a promising approach, numerous difficulties limit
      the use of these markers and prevent their application in routine practice. Let
      us hope that the new techniques for tissue analysis such as DNA or tissue-arrays
      developed for simultaneous analysis of hundreds or even thousands of tumors will
      allow identification and validation of biological and even therapeutic markers.
      Among the various biological markers, only the proliferative index given by the
      expression of Ki67, the expression of p53 and EGFR have been examined in
      comparative studies. Ki67 seems to be the best marker for progression, its
      expression and the interpretation of results being more reproducible than for
      p53.

PMID- 14597896
TI  - [Liposarcoma of the pleura: an exceptional tumor. A study of two cases].
AB  - Primitive intrathoracic liposarcomas are rare tumors mostly located in the
      mediastinum or in lung parenchyma. Primitive liposarcomas of the pleura are
      exceptional and show a dramatic clinical course. These tumors are treated by
      surgery sometimes associated with radiotherapy. We report 2 cases of primitive
      liposarcoma of the pleura occurring in 2 women of 19 and 62 years of age.
      Histological examination showed in both cases a low-grade myxoid liposarcoma. In
      one case, ultrastructural study confirmed the diagnosis.

PMID- 14597897
TI  - [Inflammatory leiomyosarcoma: a case report].
AB  - We report an additional case of inflammatory leiomyosarcoma, arising in the
      shoulder of a 31-year-old male. The rare inflammatory variant of leiomyosarcoma
      tends to affect young adults. Histologically it is characterized by a prominent
      lymphohistiocytic infiltrate often masking fascicles of spindle cells, as well as
      the presence of clusters of xanthoma cells and psammoma bodies. Smooth muscle
      differentiation is supported by desmin and smooth muscle actin expression. The
      differential diagnosis includes so-called inflammatory 'malignant fibrous
      histiocytoma'and inflammatory myofibroblastic tumor. The outcome of this variant
      seems to be favorable.

PMID- 14597898
TI  - [Mural nodules of anaplastic carcinoma in bilateral ovarian borderline mucinous
      cystadenoma: a case report].
AB  - The occurrence of mural nodules in serous or mucinous ovarian tumors is not
      frequent but is currently well established. Mural nodules can developed in
      benign, borderline or malignant tumors. They can be reactive, benign or
      malignant. In these situations, the nodule may be carcinomatous, sarcomatous or
      mixed. Thus, the prognosis of the ovarian tumor can be dramatically modified by
      the presence of this nodule. About twenty cases of mural nodules of anaplastic
      carcinoma have been described. We report an additional case of two mural nodules
      of anaplastic carcinoma associated with bilateral ovarian borderline mucinous
      tumor. This tumor was synchronous with a renal cell carcinoma. We give details
      about the classification, the differential diagnoses and prognosis of these
      nodules.

PMID- 14597899
TI  - [Misleading Kaposi's sarcoma: usefulness of anti HHV-8 immunostaining].
AB  - We report two cases of early Kaposi's sarcoma illustrating the risk of
      misdiagnosis. Both lesions showed histological features and clinical aspects that
      mimicked lymphangioendothelioma. The diagnosis of lymphangioma-like Kaposi's
      sarcoma was not made until a few years later, after the lesions had become more
      extensive and bilateral. Because of this evolution which is uncommon for a
      lymphangioendothelioma, immunohistochemical staining with anti-HHV8 antibody was
      done, and was positive in successive biopsies of our two patients. These results
      reveal that these vascular lesions had been Kaposi's sarcomas of the lymphangioma
      like type since the beginning. In conclusion, it seems essential to search for
      HHV8 within endothelial cells of any vascular lesion mimicking
      lymphangioendothelioma or any other vascular proliferation difficult to classify.
      These results lead us to question whether lymphangioendothelioma is a real
      entity.

PMID- 14597900
TI  - [Pituitary germinoma and lymphocytic hypophysitis: a pitfall. Report of two
      cases].
AB  - We report two cases of pituitary germinomas in two young men aged 13 and 21,
      revealed by insipidus diabetes associated with visual field defects or
      hypopituitarism. Neuroimaging of the first case was initially normal, then showed
      an infiltration of the stalk; the lesion of the second case appeared as a nodular
      thickening of the stalk and subsequently a pituitary infiltration. Histologically
      they mimicked lymphocytic infundibulo-neuro-hypophysitis (LINH) or lymphocytic
      hypophysitis (LH), the large tumoral clear cells being out-numbered by the heavy
      inflammatory stroma or mistaken for macrophages. Only the immuno-staining by
      placental alkaline phosphatase led to the diagnosis. In these tumours,
      immunostaining positive for CD-117 and negative for CD30, confirmed the diagnosis
      and should allow the distinction of pituitary germinoma from other germ cell
      tumours as recently described in the testis, and may have a therapeutic interest.

PMID- 14597901
TI  - [Two cases of neurocysticercosis mimicking brain tumor].
AB  - Neurocysticercosis is an infectious disorder of the central nervous system caused
      by Taenia solium larvae. We report two misleading cases, mimicking high grade
      glioma on radiology. Two patients, aged 14 and 29 respectively, developed
      seizure, associated with left facial paralysis in the second. For each case,
      radiological data revealed a solitary lesion highly suggestive of high grade
      glioma. Microscopically, within an important inflammatory process, a
      characteristic cystic formation allowed a definite diagnosis of cysticercosis.
      Then, for both patients, a history of migration from endemic area was
      demonstrated later. These cases highlight the necessary pathological examination
      when neurocysticercosis mimics a brain tumor.

PMID- 14597902
TI  - [Necrotizing lymphadenitis and hematoxylin bodies: key of the etiologic
      diagnosis].

PMID- 14597903
TI  - [Melanotic meningeal supratentorial tumour].

PMID- 14597905
TI  - [Hepatic nodules in...a hare!].

PMID- 14597904
TI  - [An increasing cholestasis].

PMID- 14597906
TI  - [Macroscopic examination of esophagectomy specimens].
AB  - Macroscopic examination of surgical specimens is an important issue for the
      treatment of patients with cancer of the esophagus. Their prognosis is based
      mainly on the degree of tumor infiltration into the esophageal wall and the
      presence of lymph node metastasis. This article describes a protocol for the
      examination of these specimens in surgical pathology departments.

PMID- 14597907
TI  - [Retrorectal solitary fibrous tumor: an uncommon localisation and a difficult
      diagnosis].

PMID- 14597908
TI  - Perinatal biochemistry and physiology of long-chain polyunsaturated fatty acids.
AB  - Docosahexaenoic acid (DHA) and arachidonic acid (ARA) are important structural
      components of the central nervous system. These fatty acids are transferred
      across the placenta, are present in human milk, and are accumulated in the brain
      and retina during fetal and infant development. The high concentrations of DHA in
      the retina and of DHA and ARA in brain gray matter suggests that these fatty
      acids have important roles in retinal and neural function. Animal studies have
      shown that depletion of DHA from the retina and brain results in reduced visual
      function and learning deficits. The latter effects may be explained by changes in
      the membrane bilayer that alter membrane-associated receptors and signal
      transduction systems, ion channel activity, or direct effects on gene expression.
      DHA can be formed in the liver from alpha linolenic acid, but it is unclear if
      the rate of DHA synthesis in humans is sufficient to support optimal brain and
      retinal development. Although there is no evidence that the ability to form ARA
      from linoleic acid is limiting, supplementation with DHA reduces tissue ARA,
      possibly creating a conditional need for ARA in infants with a dietary intake of
      DHA. The amount of DHA in human milk varies widely and is positively correlated
      with visual and language development in breast-fed infants. Advances in
      understanding essential fatty acid requirements will benefit from intervention
      studies that use functionally relevant tests to probe the deficiency or adequacy
      of physiologically important pools of DHA and ARA in developing infants.

PMID- 14597909
TI  - Plausible mechanisms for effects of long-chain polyunsaturated fatty acids on
      growth.
AB  - A few studies conducted over the past decade suggest that formulas supplemented
      with long-chain polyunsaturated n-3 fatty acids may adversely affect growth of
      preterm infants. Others suggest that a high intake of alpha-linolenic acid (ALA;
      18:3 n-3), the precursor of the long-chain polyunsaturated n-3 fatty acids, also
      may limit growth. The majority of studies, however, have not shown an effect of
      either long-chain polyunsaturated n-3 fatty acids or their precursor on growth.
      Nonetheless, the importance of growth during infancy and the possibility that
      these fatty acids may inhibit growth under some circumstances makes the issue
      worthy of further consideration. At the very least, plausible mechanisms for such
      an effect of n-3 PUFA on growth should be considered. These include (1) altered
      nutrient intake, absorption, and/or utilization; (2) low plasma and tissue
      contents of arachidonic acid (ARA;20:4 n-6); (3) an imbalance between n-6 and n-3
      LCPUFA eicosanoid precursors and, hence, the eicosanoids produced from each; (4)
      altered membrane characteristics; and (5) effects on gene expression. Each of
      these is discussed. It is concluded that any or all are feasible but that none
      can be specifically implicated. Moreover, since few studies were designed
      specifically to assess growth, the reported effects of n-3 PUFA on growth could
      represent chance findings secondary to the suboptimal design. Furthermore,
      although additional data are needed for a definitive conclusion, the observed
      effects on growth, regardless of mechanism, does not appear to be biologically
      significant.

PMID- 14597910
TI  - Term infant studies of DHA and ARA supplementation on neurodevelopment: results
      of randomized controlled trials.
AB  - Healthy term infants who are not breast-fed may need long-chain polyunsaturated
      fatty acids (LCPUFA) in their feeding, based on the changes in plasma and tissue
      fatty composition. However, consistent functional effects across different
      studies conducted over the past two decades has been more difficult to document.
      The interpretation of these data has scientific and public interest with the
      introduction of LCPUFA supplemented formula. There are 14 controlled trials in
      term infants that have included formula feeding with or without LCPUFA and
      functional assessment of visual and other measures of neural development; in
      addition, 7 have evaluated specific measures related to cognitive development. We
      chose to examine the effect of DHA dose provided daily on the development of
      visual acuity to explain the differences in visual acuity responses across
      randomized studies. A "meta-regression" was performed with the use of a DHA
      effective dose as the independent variable and visual acuity at 4 months as the
      dependent variable. Since the two main dietary determinants of DHA status are the
      LNA provided and the preformed DHA consumed, we defined DHA equivalent dose
      across studies by assuming a 1%, 5%, and 10% conversion of LNA to DHA. Results
      indicate a strong and significant effect of DHA equivalent dose on magnitude of
      the visual acuity response at all conversions tested; greatest significance was
      found when using a 10% bioequivalency (r(2)=0.68, and P=.001). We conclude that
      there is a significant relation between the total DHA equivalents provided and
      effectiveness as defined by visual acuity measurements at 4 months of age.

PMID- 14597911
TI  - In vivo approaches to quantifying and imaging brain arachidonic and
      docosahexaenoic acid metabolism.
AB  - A novel in vivo fatty acid method has been developed to quantify and image brain
      metabolism of nutritionally essential polyunsaturated fatty acids (PUFAs). In
      unanesthetized rodents, a radiolabeled PUFA is injected intravenously, and its
      rate of incorporation into brain phospholipids is determined by chemical analysis
      or quantitative autoradiography. Results indicate that about 5% of brain
      arachidonic acid (20:4 n-6) and of docosahexaenoic acid (22:6 n-3) acid are lost
      daily by metabolism and are replaced from dietary sources through the plasma.
      Calculated turnover rates of PUFAs in brain phospholipids, due to
      deesterification by phospholipase A(2) (PLA(2)) followed by reesterification, are
      very rapid, consistent with active roles of PUFAs in signal transduction and
      other processes. Turnover rates of arachidonate and docosahexaenoate are
      independent of each other and probably are regulated by independent sets of
      enzymes. Brain incorporation of radiolabeled arachidonate can be imaged in
      response to drugs that bind to receptors coupled to PLA(2) through G proteins,
      thus measuring PLA(2)-initiated signal transduction. The in vivo fatty method is
      being extended for human studies using positron emission tomography.

PMID- 14597912
TI  - Structural and functional maturation of the developing primate brain.
AB  - Descriptive studies have established that the developmental events responsible
      for the assembly of neural systems and circuitry are conserved across mammalian
      species. However, primates are unique regarding the time during which
      histogenesis occurs and the extended postnatal period during which myelination of
      pathways and circuitry formation occur and are then subsequently modified,
      particularly in the cerebral cortex. As in lower mammals, the framework for
      subcortical-cortical connectivity in primates is established before midgestation
      and already begins to remodel before birth. Association systems, responsible for
      modulating intracortical circuits that integrate information across functional
      domains, also form before birth, but their growth and reorganization extend into
      puberty. There are substantial differences across species in the patterns of
      development of specific neurochemical systems. The complexity is even greater
      when considering that the development of any particular cellular component may
      differ among cortical areas in the same primate species. Developmental and
      behavioral neurobiologists, psychologists, and pediatricians are challenged with
      understanding how functional maturation relates to the evolving anatomical
      organization of the human brain during childhood, and moreover, how genetic and
      environmental perturbations affect the adaptive changes exhibited by neural
      circuits in response to developmental disruption.

PMID- 14597913
TI  - Assessing brain development using neurophysiologic and behavioral measures.
AB  - One critical aspect of pediatric research is the assessment of outcome measures
      after treatment or intervention. Behavioral measures of physical growth, school
      achievement, and general intelligence have proven to be important scales for
      assessing gross developmental outcome and differences between pediatric treatment
      groups. However, more subtle and sophisticated measures may be required to assess
      finer grained differences in brain development at the structural and functional
      levels. Advances in noninvasive brain imaging techniques over the past decade
      have improved our ability to link specific cognitive functions to changes in
      brain structure and function in healthy infants and children. This paper
      highlights some of the ways that electrophysiologic and functional magnetic
      resonance imaging methods have been combined with behavioral measures of
      cognitive and emotional function to advance our understanding of brain-behavior
      relations. Such combined neurophysiologic and behavioral methods may help to
      identify the role specific interventions have on long-term developmental outcomes
      in childhood.

PMID- 14597914
TI  - The building blocks of cognition.
AB  - This article provides an overview of some innovative ways of examining infant
      cognition, highlighting several procedures that are likely to prove useful for
      assessing the effects of interventions in the first year of life. The procedures
      singled out assess three aspects of cognition in infancy: visual recognition
      memory, attention, and speed of processing. Assessments of each, while primarily
      experimental in nature, show strong developmental change over the first year, as
      well as modest stability, discriminant validity, and predictive validity. The
      emerging evidence suggests that these three aspects of infant cognition are among
      the most basic building blocks of mature cognition.

PMID- 14597915
TI  - Baby steps to learning language.
AB  - Young infants show remarkable speech perception sensitivities, and during the
      first year of life narrow these initial capabilities to reflect enhanced
      sensitivity to the sounds and structures used in their native language. This
      article reviews critical research illustrating how infants tune their perceptual
      sensitivities during the first year of life and how the language-specific changes
      in perception help "bootstrap" them into language. Specific discussion centers on
      recent research from our lab showing a link between the advances in speech
      perception and subsequent word learning in both normally developing and clinical
      populations, including research on the impact of early nutrition. The article
      ends with suggestions for new ways in which the milestones in speech and language
      processing seen in infancy can serve to help assess the role of early nutrition
      on subsequent development.

PMID- 14597916
TI  - Sleep-wake states and their regulatory mechanisms throughout early human
      development.
AB  - The emergence of sleep states is one of the most significant aspects of
      development. Descriptions of both neonatal and late fetal behavior and studies on
      the organization of sleep have shown that fetus and newborns exhibit
      spontaneously discrete and cyclic patterns of active sleep (AS) and quiet sleep
      (QS). Human fetuses and neonates sleep most of their life, and AS is the
      prevailing state even during the first postnatal months. Several hypotheses to
      explain central nervous system development consider that AS is the expression of
      a basic activation program for the central nervous system that increases the
      functional competence of neurons, circuits, and complex patterns before the
      organism is called on to use them. Current results indicate the maturation of QS
      not only coincides with the formation of thalamocortical and intracortical
      patterns of innervation and periods of heightened synaptogenesis, since this
      sleep state is also associated with important processes in synaptic remodeling.
      In fact, several studies suggest that the information acquired during wakefulness
      is further processed during AS and QS. This article reviews the processes
      involved in the timing of both AS/QS and sleep/wake alternating patterns
      throughout early human development. A growing body of evidence indicates that the
      duration of unmodulated parental care and noncircadian environmental conditions
      may be detrimental for the establishment of these basic rhythmicities. As a
      consequence, alterations in parental/environmental entraining factors may well
      contribute to disturb sleep and feeding commonly experienced by preterm infants.
      Further knowledge on the early establishment of sleep-wake states regulatory
      mechanisms is needed to improve modalities for appropriate stimulation in the
      developing human being.

PMID- 14597918
TI  - Visual development: Neural basis and new assessment methods.

PMID- 14597917
TI  - DHA-rich phospholipids optimize G-Protein-coupled signaling.
AB  - OBJECTIVE: To assess the effects of n-3 polyunsaturated phospholipid acyl chains
      on the initial steps in G-protein-coupled signaling. STUDY DESIGN: Isolated
      components of the visual signal transduction system, rhodopsin, G protein (G(t)),
      and phosphodiesterase (PDE), were reconstituted in membranes containing various
      levels of n-3 polyunsaturated phospholipid acyl chains. In addition, rod outer
      segment disk membranes containing these components were purified from rats raised
      on n-3-deficient and n-3-adequate diets. The conformation change of rhodopsin,
      coupling of rhodopsin to G(t), and PDE activity were each measured separately.
      RESULTS: The ability of rhodopsin to form the active metarhodopsin II
      conformation and bind G(t) were both compromised in membranes with reduced levels
      of n-3 polyunsaturated acyl chains. The activity of PDE, directly related to the
      integrated cellular response, was reduced in all membranes lacking or deficient
      in n-3 polyunsaturated acyl chains. PDE activity in membranes containing 22:5n-6
      PC was 50% lower than in membranes containing either 22:6n-3 PC or 22:5n-3 PC.
      CONCLUSIONS: The earliest events in G-protein-coupled signaling; receptor
      conformation change, receptor-G-protein binding, and PDE activity are reduced in
      membranes lacking n-3 polyunsaturated acyl chains. Efficient and rapid
      propagation of G-protein-coupled signaling requires polyunsaturated n-3
      phospholipid acyl chains.

PMID- 14597919
TI  - Mechanisms of Action of LCPUFA Effects on Infant Growth and Neurodevelopment.
      Arlington, Virginia, USA. May 14-15, 2002. Symposium proceedings.

PMID- 14597920
TI  - Noninvasive assessment of reperfusion therapy: slow progress towards a worthwhile
      goal.

PMID- 14597921
TI  - Pacing in elderly patients.

PMID- 14597922
TI  - New insight into clinical risk scores for patients with acute coronary syndromes.

PMID- 14597923
TI  - "Mirror-lake" serial relationship of electrocardiographic and biochemical indices
      for the detection of reperfusion and the prediction of salvage in patients with
      acute myocardial infarction.
AB  - BACKGROUND: Serial observations of biochemical markers in the blood and
      bioelectric markers on the electrocardiogram (ECG) have been used to evaluate the
      effectiveness of reperfusion therapy in acute myocardial infarction (AMI). This
      study presents a combined method for clinical use, based on the "mirror-lake"
      tendency of the serial changes in these markers. METHODS: Consecutive
      thrombolytic-treated patients with AMI (n = 43) had ST-segment monitoring
      (Mortara Eli 100) and frequent serum sampling of myoglobin (MG) concentration.
      Their acutely predicted and finally estimated AMI sizes and myocardial salvage
      extents were calculated from the 12-lead standard ECG. Patients having 2 positive
      reperfusion indices (ST resolution at least 50%, and an increase in MG at least
      2.4 fold) at 2 hours after initiation of thrombolytic therapy were considered the
      "complete reperfusion" group, and patients with discordant or 2 negative
      reperfusion indices after 2 hours of thrombolytic therapy were considered the
      "limited reperfusion" group. RESULTS: Patients with complete reperfusion (n = 22)
      versus patients with limited reperfusion (n = 21) had +12% versus -1% myocardial
      salvage (P <.0001). The serial changes in the ST segment mirrored the serial
      changes in the MG concentration, and the rates of increase in MG correlated with
      the rates of resolution of the ST-segment elevation. CONCLUSION: Myocardial
      salvage (measured by ECG indices) is greatest when an early increase in serum MG
      is "mirrored" by early resolution of ST-segment elevation.

PMID- 14597924
TI  - Optimizing glycoprotein IIb/IIIa receptor antagonist use for the non-ST-segment
      elevation acute coronary syndromes: risk stratification and therapeutic
      intervention.
AB  - Despite extensive data supporting their use for non-ST-segment elevation acute
      coronary syndromes, glycoprotein (GP) IIb/IIIa antagonists are underutilized.
      This is likely the consequence of confusion as to which patients should receive
      these agents, as well as to the most appropriate timing and venue for their
      initiation. We will review the advances in the understanding of GP IIb/IIIa
      antagonist therapy, emphasizing methods of identifying those most likely to
      benefit from the use of GP IIb/IIIa receptor blockade. In addition, we will
      consider appropriate methods/venues for use of GP IIb/IIIa receptor antagonism,
      including its role in an "early invasive" catheterization strategy.

PMID- 14597925
TI  - Intracoronary brachytherapy for the prevention of restenosis after percutaneous
      coronary revascularization.
AB  - PURPOSE: The purpose of this article is to review the current literature
      pertaining to intracoronary brachytherapy for the prevention of restenosis after
      percutaneous coronary revascularization (PCR). METHODS: English-language articles
      were identified through a MEDLINE search (January 1984 to January 2003) using the
      keywords brachytherapy, radioactive stents, and coronary arteries. In addition,
      pertinent reference citations from relevant articles were reviewed. RESULTS:
      Restenosis after PCR is a complex process, thought to be due to a combination of
      vessel wall remodeling and neointimal proliferation. To date, catheter-based
      delivery of intracoronary brachytherapy has been found to prevent vessel wall
      remodeling and causes a reduction in the proliferation of the neointima.
      Neointimal proliferation, as measured by mean neointimal area, was reduced in all
      animal studies (range 26%-91%). In contrast, animal studies examining radioactive
      stents demonstrated an increase in neointimal proliferation, suggesting that they
      may not be helpful at preventing post-PCR restenosis. All human studies using
      catheter-based intracoronary brachytherapy for in-stent restenosis have employed
      either beta (beta) or gamma (gamma) radiation sources with variable doses of
      radiation (range 7-56 Grays [Gy]). Restenosis occurred in 12% to 40% of patients
      in nonrandomized studies, and clinical events occurred in 13% to 50% of patients.
      To date, there have been 7 published randomized trials in humans comparing
      catheter-based intracoronary brachytherapy to placebo, with a total of 1047
      patients. The dose of radiation in the trials ranged from 14 Gy to 30 Gy. During
      follow-up, 8% to 33% of patients who received brachytherapy had restenosis versus
      39% to 64% of patients receiving placebo. Clinical events occurred in 19% to 50%
      among patients who received brachytherapy versus 29% to 79% among patients
      receiving placebo. The majority of human studies examining radioactive stents do
      not demonstrate a reduction in restenosis in patients post-PCR. There are no
      randomized trials examining radioactive stents in humans. CONCLUSION:
      Nonrandomized studies of radioactive stents suggest they are not effective at
      preventing in-stent restenosis. In contrast, data from animal and human studies
      suggest that catheter-based intracoronary brachytherapy can prevent in-stent
      restenosis and reduce clinical events post-PCR.

PMID- 14597926
TI  - Percutaneous coronary intervention: historical perspectives, current status, and
      future directions.
AB  - In the twenty-six years since Gruntzig introduced a simple balloon angioplasty
      technique, percutaneous coronary intervention has undergone extraordinary growth
      and has now surpassed bypass surgery in frequency of performance. Several
      critical breakthrough technologies account for this remarkable progress:
      intracoronary stents have increased success rates and reduced restenosis,
      adjunctive antiplatelet therapy has reduced periprocedural complications, and
      restenosis after stent placement has been effectively treated with local
      radiation. Most recently, drug-eluting stents coated with cell-cycle inhibitors
      have shown great promise for further reducing restenosis, possibly to negligible
      levels.

PMID- 14597927
TI  - A modified Anderson-Wilkins electrocardiographic acuteness score for anterior or
      inferior myocardial infarction.
AB  - BACKGROUND: Optimal treatment of acute myocardial infarction (AMI) depends on the
      duration of the ischemia. The Anderson Wilkins (AW) electrocardiographic
      acuteness score has been shown to complement the historical timing in estimating
      the time interval from acute thrombotic coronary occlusion in patients presenting
      with chest pain and evolving myocardial infarction. The purposes of this study
      were to (1) compare the distributions of the previously developed AW acuteness
      score in a training population with either anterior or inferior AMI and (2)
      propose modifications to the formula to achieve distributions similar to the
      observed distributions of historical times from onset of pain. METHODS: Two
      hundred three and 177 patients were included as training and testing population,
      respectively. All patients had an anterior or an inferior AMI and were without
      confounding factors on the electrocardiogram. RESULTS: The training population
      had similar distributions of historical times from onset of pain, but differences
      in distributions of AW acuteness scores, between patients with anterior and
      inferior AMI (P <.0001). Eighty percent of the inferior AMI group had the highest
      possible AW acuteness score. Modification of a Q-wave criterion from > or =30 to
      > or =20 ms resulted in similar distributions in patients with anterior and
      inferior AMI both in the training and an independent testing population.
      CONCLUSIONS: These results suggest that a modified AW acuteness score using a
      lower Q-wave duration criterion provides similar AMI timing information in
      patients with anterior and inferior locations. Clinical use of the AW acuteness
      score will only be practical if the calculation is automated.

PMID- 14597929
TI  - Association of the PURSUIT risk score with predischarge ejection fraction,
      angiographic severity of coronary artery disease, and mortality in a nonselected,
      community-based population with non-ST-elevation acute myocardial infarction.
AB  - BACKGROUND: The Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor
      Suppression Using Integrilin Therapy (PURSUIT) risk score was derived from the
      PURSUIT trial population for 30-day mortality prediction. METHODS: The PURSUIT
      risk score was calculated for 337 consecutive Olmsted County residents with non
      ST-elevation acute myocardial infarction admitted to the coronary care unit of
      our institution from 1988 through 1998. Predischarge ejection fraction (EF)
      measurement was available for 246 patients (73%). After excluding patients with
      prior coronary artery bypass graft surgery (n = 42), 219 patients (65%) had
      coronary angiography within 30 days of admission. Mortality at 30 days was 8.9%.
      Among 30-day survivors, mortality at 1 year was 7.9%. RESULTS: Mean age was 70 +/
      13 years, and 37% of patients were women. Mean predischarge EF was 52% +/- 16%.
      Patients with higher PURSUIT risk score had lower EF (P <.001). Three-vessel (>
      or =70% stenosis in all 3 coronary arteries) or left main (> or =50% stenosis)
      coronary artery disease was present in 60 of 219 patients (27%) who had coronary
      angiography. Higher PURSUIT risk score was associated with greater likelihood of
      3-vessel or left main disease (P <.001). The PURSUIT risk score had very good
      predictive accuracy for both early (30-day, C-statistic = 0.78) and late (30-day
      to 1-year, C-statistic = 0.77) mortality. CONCLUSIONS: The PURSUIT risk score
      correlates with EF, angiographic severity of coronary artery disease, and short-
      and long-term mortality of nonselected patients with non-ST-elevation acute
      myocardial infarction.

PMID- 14597928
TI  - Influence of thrombolytic therapy, with or without intra-aortic balloon
      counterpulsation, on 12-month survival in the SHOCK trial.
AB  - BACKGROUND: The enhancement of diastolic coronary blood flow by the combination
      of thrombolytic therapy (TT) and intra-aortic balloon counterpulsation (IABP) in
      experimental studies provides a rationale for their combined use in acute
      myocardial infarction (MI) complicated by cardiogenic shock. We examined the
      relation between TT (with and without IABP) and 12-month survival in the SHould
      We Emergently Revascularize Occluded Coronaries for Cardiogenic ShocK (SHOCK)
      Trial. METHODS AND RESULTS: Among 302 patients with myocardial infarction and
      cardiogenic shock who were randomized in the SHOCK Trial, 16 had absolute
      contraindications to TT. Among 150 patients randomly assigned to initial medical
      stabilization (IMS), 63% received TT, as recommended per protocol, compared with
      49% of 152 patients randomly assigned to emergency revascularization, in whom TT
      was not recommended if immediate angiography was available. IABP deployment,
      which was protocol-recommended, was used in 86% of patients. The rate of severe
      bleeding was similar in patients receiving TT and in those not receiving TT (31%
      vs 26%, P =.37). Among patients randomly assigned to IMS, TT was associated with
      improved 12-month survival (unadjusted mortality hazard ratio, 0.59; P =.01;
      mortality hazard ratio adjusted for age and prior MI, 0.62; P =.02). TT was not
      associated with improved 12-month survival among patients randomly assigned to
      emergency revascularization (unadjusted mortality hazard ratio, 0.93; P =.76;
      mortality hazard ratio adjusted for age and prior MI, 1.06, P =.81). The test for
      interaction of TT and randomization group P value was.16, and there was
      insufficient statistical power to demonstrate a differential effect of TT on 12
      month survival by treatment group assignment. CONCLUSIONS: Among patients
      randomly assigned to IMS in the SHOCK Trial, TT was associated with improved 12
      month survival and did not significantly increase the risk of severe bleeding.

PMID- 14597930
TI  - Diagnostic coronary angiography induces a systemic inflammatory response in
      patients with stable angina.
AB  - BACKGROUND: Systemic markers of inflammation increase after percutaneous coronary
      intervention (PCI). The rise in inflammatory markers after PCI is frequently
      attributed to the inflammatory stimulus associated with coronary artery injury
      during balloon inflation and coronary stent implantation. The aim of this study
      was the determine whether diagnostic coronary angiography performed in patients
      with stable angina triggers a systemic inflammatory response. METHODS: We
      prospectively studied patients with chronic stable angina undergoing either
      coronary angiography (n = 13) or coronary angiography followed by PCI (n = 13).
      Peripheral blood samples were obtained before and 24 hours, 48 hours, and 4 weeks
      after the procedure and analyzed for C-reactive protein (CRP), interleukin-6 (IL
      6), and tumor necrosis factor-alpha (TNF-alpha). Patients with periprocedural
      myocardial necrosis were excluded. RESULTS: There was a significant increase in
      CRP levels at 24 and 48 hours in both the coronary angiography (P <.05) and PCI
      (P <.01) groups. IL-6 levels peaked at 24 hours in both the coronary angiography
      (median, 2.5-9.5 pg/mL; P =.01) and PCI (median, 3.0-8.2 pg/mL; P <.005) groups.
      At 4 weeks, both CRP and IL-6 returned to baseline levels. TNF-alpha levels were
      unchanged with either coronary angiography or PCI. The magnitude of the rise of
      CRP and IL-6 levels was not significantly different between the groups. There was
      a fair correlation between baseline and peak postprocedural levels of CRP (r =
      0.67, P =.008) and IL-6 (r = 0.48, P =.016). CONCLUSION: Uncomplicated diagnostic
      coronary angiography triggers a systemic inflammatory response in patients with
      stable angina. The contribution of coronary angiography should be considered in
      interpreting the significance of the systemic inflammatory response observed
      after PCI.

PMID- 14597931
TI  - Sex differences in survival after acute myocardial infarction in patients with
      diabetes mellitus (Worcester Heart Attack Study).
AB  - BACKGROUND: Women with diabetes mellitus are at particularly high risk for
      coronary heart disease-related morbidity and mortality compared with men with
      diabetes mellitus. However, recent data comparing hospital and long-term outcomes
      in women with diabetes mellitus and men hospitalized with acute myocardial
      infarction (AMI) are scarce. The objectives of our multi-hospital observational
      study were to examine sex differences and temporal trends (1975-99) in hospital
      and long-term case-fatality rates (CFRs) in patients with diabetes mellitus and
      AMI from a population-based perspective. METHODS: A community-wide study of
      residents of the Worcester, Mass, metropolitan area who were hospitalized with
      confirmed AMI was conducted. Data were collected in 12 1-year periods between
      1975 and 1999. The study sample consisted of 1354 men and 1280 women with
      diabetes mellitus. RESULTS: Overall hospital CFRs were significantly greater for
      women with diabetes mellitus (21.3%) than for men with diabetes mellitus (14.9%).
      Between 1975 and 1999, hospital CFRs declined from 39.2% to 17.5% for women and
      from 18.9% to 9.5% in men. In examining long-term survival patterns for as long
      as 10 years after hospital discharge, there were no significant sex differences
      in long-term survival rates after adjustment for a limited number of known
      potentially confounding factors. CONCLUSIONS: Hospital death rates after AMI in
      men and women with diabetes mellitus have declined in the last 2 decades. The gap
      in hospital CFRs between men and women with diabetes mellitus has decreased
      considerably with time, although women have a higher risk of dying after AMI than
      men. Patients with diabetes mellitus continue to represent a high-risk group who
      will benefit from enhanced surveillance efforts and increased use of effective
      cardiac treatments.

PMID- 14597932
TI  - Acute coronary syndromes in patients with prior cerebrovascular events: lessons
      from the Euro-Heart Survey of Acute Coronary Syndromes.
AB  - BACKGROUND: The aim of this study was to determine the frequency of prior
      cerebrovascular events (CE) among patients with an acute coronary syndrome (ACS)
      and to compare the clinical characteristics, clinical course, treatment, and
      outcomes of patients with ACS with and without a prior CE. METHODS AND RESULTS:
      We prospectively enrolled 10,484 patients with ACS in 103 hospitals in 25
      countries across Europe and the Mediterranean basin. A prior CE was reported in
      254 of 4338 patients (5.9%) with ST elevation, 420 of 5215 patients (8.1%)
      without ST elevation, and 92 of 663 patients (13.9%) with an undetermined
      electrocardiographic pattern. In general, patients with a prior CE were older,
      more likely to be females and nonsmokers, more commonly had prior myocardial
      infarction, heart failure, bypass surgery, and were more likely to have diabetes,
      hypertension, and renal failure. While in the hospital, they had more heart
      failure, and they were more likely to receive warfarin, digoxin, diuretics and
      calcium-channel blockers, and less likely to receive antiplatelet agents, beta
      blockers, and statins. The inhospital mortality rates were 9.1% (with a prior CE)
      versus 6.4% (without a prior CE) for patients with ACS with ST elevation; 5.0%
      versus 2.0% for patients with ACS with non-ST elevation; and 14.1% versus 10.7%
      for patients with ACS with undetermined electrocardiographic results. The
      adjusted risk (95% CI) of inhospital death for patients with a prior CE was 1.12
      (0.70, 1.81), 1.79 (1.06, 3.00), and 0.92 (0.44, 1.94) for ST-elevation ACS, non
      ST-elevation ACS, and ACS with undetermined electrocardiogram, respectively. The
      P value for interaction between prior CE and the type of ACS on outcome was.10.
      CONCLUSIONS: Patients with a prior CE constitute 7.5% of patients with ACS and
      have high-risk features. A prior CE is associated with increased inhospital
      mortality, particularly in patients with with non-ST-elevation ACS.

PMID- 14597933
TI  - Is there evidence of implicit exclusion criteria for elderly subjects in
      randomized trials? Evidence from the GUSTO-1 study.
AB  - BACKGROUND: Some experts have raised concerns about the ability to generalize
      randomized trials, emphasizing that patients who participate in these studies are
      often not representative of those seen in clinical practice, particularly in the
      case of elderly patients. To determine the effect of implicit exclusion criteria
      on a trial study sample, we compared data from the Global Utilization of
      Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) trial with data
      from a retrospective registry from selected hospitals, the National Registry of
      Myocardial Infarction (NRMI), and a nationally representative study of myocardial
      infarction care, the Cooperative Cardiovascular Project (CCP). METHODS: We
      compared GUSTO subjects aged 65 years and older who were enrolled in the United
      States with similarily aged patients in the 2 observational studies who met the
      trial's eligibility criteria. We examined baseline characteristics, clinical
      presentation, treatments, procedures, clinical events, and in-hospital mortality
      rates. RESULTS: We found modest, although significant, differences between
      patients in NRMI, CCP, and GUSTO in demographic and clinical characteristics,
      treatment, and outcome. For example, GUSTO patients were significantly younger
      (73.1 +/- 5.7 vs 74.7 +/- 6.8 for NRMI and 75.8 +/- 7.2 for CCP), less likely to
      have Killip class III/IV at presentation (3.1% vs 6.2% for NRMI and 32.7% for
      CCP), and more likely to receive aspirin (95.5% vs 86.3% for NRMI and 86.5% for
      CCP) and beta-blockers (71.9% vs 43.5% for NRMI and 52.7% for CCP). Overall, NRMI
      and CCP patients had a lower risk of 30-day mortality after adjustment for
      demographic, clinical, and hospital characteristics than patients in GUSTO (odds
      ratio, 0.79; 95% CI, 0.73-0.86 for NRMI; odds ratio, 0.65; 95% CI, 0.59-0.71 for
      CCP). CONCLUSIONS: Older patients enrolled in a randomized trial without an age
      restriction had many similarities compared with patients seen in clinical
      practice. The higher mortality rate of the GUSTO patients does not support the
      hypothesis that the trial enrolled a healthier cohort than is seen in practice.

PMID- 14597934
TI  - Are beta-blockers as efficacious in patients with diabetes mellitus as in
      patients without diabetes mellitus who have chronic heart failure? A meta
      analysis of large-scale clinical trials.
AB  - BACKGROUND: Diabetes mellitus is a frequent comorbid condition in patients with
      chronic heart failure (CHF) and confers a worse prognosis. Furthermore, although
      patients with CHF derive considerable benefit from beta-blockers, these agents
      are thought by many physicians to be contraindicated in patients with diabetes
      mellitus. Most published studies on beta-blockers in CHF have been unable to
      reach definitive conclusions about the mortality benefits of these agents in
      patients with diabetes mellitus. We therefore performed a meta-analysis of beta
      blocker trials that reported mortality outcomes in patients with diabetes
      mellitus who had CHF to pool all available trial evidence on the benefits (or
      otherwise) of these agents in this setting. METHODS: All-cause mortality data on
      patients with diabetes mellitus were obtained from all completed beta-blocker CHF
      randomized placebo-controlled trials involving >100 patients exposed to beta
      blockers, in which outcomes in patients with diabetes mellitus were described.
      When events were not directly reported, risk ratios (RRs) were derived from
      analysis of figures and other manuscript data. Results were pooled with the
      Mantel-Haenszel method. RESULTS: A total of 24.6% of patients were reported to
      have diabetes mellitus in the 6 studies analyzed (Australia and New Zealand [ANZ]
      Carvedilol, Beta-blocker Evaluation of Survival Trial [BEST], Carvedilol US
      Trials, Cardiac Insufficiency Bisoprolol Study [CIBIS-II], Carvedilol Prospective
      Randomized Cumulative Survival Trial [COPERNICUS], and Metoprolol Controlled
      release Randomized Intervention Trial in Heart Failure [MERIT-HF]). Patients with
      diabetes mellitus had increased mortality rates overall compared with subjects
      without diabetes mellitus (RR, 1.25; 95% CI, 1.15-1.36; P <.001). Compared with
      placebo, beta-blocker therapy for CHF was beneficial in patients with diabetes
      mellitus (RR, 0.84; 95% CI, 0.73-0.96; P =.011) and in subjects without diabetes
      mellitus (RR, 0.72; 95% CI, 0.65-0.79; P <.001). The absolute risk reduction in
      mortality with beta-blocker therapy was greater in patients with heart failure
      but without diabetes mellitus than in patients with diabetes mellitus (P =.023).
      CONCLUSIONS: Patients with diabetes mellitus and CHF appear to derive prognostic
      benefit from beta-blocker therapy, although the magnitude of that benefit is
      somewhat less than that observed in subjects without diabetes mellitus.

PMID- 14597935
TI  - 4G/5G polymorphism of the plasminogen activator inhibitor-1 gene and risk of
      restenosis after coronary artery stenting.
AB  - BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1) has been proposed as a
      candidate risk factor for restenosis after coronary artery stenting.
      Transcription, level, and activity of PAI-1 are influenced by the 4G/5G
      polymorphism in the promoter region of PAI-1 gene. The polymorphism may therefore
      affect wound-healing processes in injured blood vessels and influence restenosis.
      METHODS: In 1850 consecutive patients, angiographic measures of restenosis and
      the clinical outcome at 30 days and 1 year after stent implantation were
      evaluated. Angiographic restenosis was defined as > or =50% diameter stenosis
      determined at follow-up angiography, performed 6 months after stenting. The 4G/5G
      genotypes were determined with TaqMan technique. RESULTS: Among the patients, the
      frequency of the 4G allele was 0.55. Follow-up angiography was done in 84% of the
      patients. We observed restenosis in 32.5% of 4G/4G carriers, 32.2% of 4G/5G
      carriers, and 35.7% of 5G/5G carriers (P =.52). The occurrence of a major adverse
      event (death, myocardial infarction, or target vessel revascularization due to
      restenosis-induced ischemia) was 5.6% in 4G/4G carriers, 5.3% in 4G/5G carriers,
      and 4.6% in 5G/5G carriers at 30 days (P =.80), and 24.7% in 4G/4G carriers,
      23.0% in 4G/5G carriers, and 26.2% in 5G/5G carriers at 1 year (P =.45).
      CONCLUSION: The 4G/5G polymorphism of the PAI-1 gene is not associated with an
      increased risk of thrombotic and restenotic events after coronary artery
      stenting.

PMID- 14597936
TI  - Effect on high-density lipoprotein cholesterol of maximum dose simvastatin and
      atorvastatin in patients with hypercholesterolemia: results of the Comparative
      HDL Efficacy and Safety Study (CHESS).
AB  - BACKGROUND: Previous studies have shown that effects on high-density lipoprotein
      cholesterol (HDL-C) may differ among statins. METHODS: A multicenter, randomized,
      double-blind, parallel-dose study was conducted in 917 hypercholesterolemic
      patients to compare the efficacy of 80 mg/d simvastatin versus 80 mg/d
      atorvastatin on HDL-C and apolipoprotein (apo) A-I for 24 weeks. Efficacy was
      assessed as the means of weeks 6 and 12 and weeks 18 and 24. Prespecified
      subgroups analyzed were patients with low HDL-C levels and with the metabolic
      syndrome. RESULTS: Simvastatin increased HDL-C and apo A-I values significantly
      more than did atorvastatin for the mean of weeks 6 and 12 (8.9% vs 3.6% and 4.9%
      vs -0.9%, respectively) and the mean of weeks 18 and 24 (8.3% vs 4.2% and 3.7% vs
      -1.4%). These differences were observed across both baseline HDL-C subgroups (<40
      mg/dL, > or =40 mg/dL) and in patients with the metabolic syndrome. Low-density
      lipoprotein cholesterol and triglyceride reductions were greater with
      atorvastatin. Consecutive elevations >3x the upper limit of normal in alanine
      aminotransferase (ALT) and/or aspartate aminotransferase (AST) occurred in
      significantly fewer patients treated with simvastatin than with atorvastatin
      (2/453 [0.4%] vs 13/464 [2.8%]), with most elevations observed in women taking
      atorvastatin (11/209 [5.3%] vs 1/199 [0.5%] for simvastatin). CONCLUSIONS:
      Simvastatin (80 mg) increased HDL-C and apo A-I significantly more than did
      atorvastatin (80 mg) in patients with hypercholesterolemia. This advantage was
      observed regardless of HDL-C level at baseline or the presence of the metabolic
      syndrome. Significantly fewer consecutive elevations >3x the upper limit of
      normal in ALT and/or AST occurred in patients receiving simvastatin.

PMID- 14597937
TI  - Lipid changes on hormone therapy and coronary heart disease events in the Heart
      and Estrogen/progestin Replacement Study (HERS).
AB  - BACKGROUND: Despite the effect of lowering low-density lipoprotein cholesterol
      (LDL-C) levels and raising high-density lipoprotein cholesterol (HDL-C) levels,
      combination hormone therapy did not reduce the incidence of coronary heart
      disease (CHD) events in the Heart and Estrogen/progestin Replacement Study
      (HERS). To explore possible mechanisms, we examined the association between lipid
      changes and CHD outcomes among women assigned to hormone therapy. METHODS: HERS
      participants were postmenopausal women with previously diagnosed CHD who were
      randomly assigned to receive conjugated estrogens and medroxyprogesterone or
      identical placebo and then followed-up for an average of 4.1 years. Among women
      assigned to hormone therapy, associations between baseline-to-year-1 lipid level
      changes and CHD events were compared with the associations observed for baseline
      lipids using multivariate proportional hazards models. RESULTS: Among women
      assigned to hormone therapy, CHD events were independently predicted by baseline
      LDL-C levels (relative hazard [RH] 0.94 per 15.6 mg/dL decrease, 95% CI 0.88
      1.01) and HDL-C levels (RH 0.89 per 5.4 mg/dL increase, 95% CI 0.81-0.99), but
      not by triglyceride levels (RH 1.01 per 13.2 mg/dL increase, 95% CI 0.97-1.06).
      CHD events were marginally associated with first-year reductions in LDL-C levels
      (RH 0.95 per 15.6 mg/dL decrease, 95% CI 0.86-1.04), and were not associated with
      increases in HDL-C levels ( RH 1.03 per 5.4 mg/dL increase, 95% CI 0.91-1.16) or
      triglyceride levels (RH 1.01 per 13.2 mg/dL increase, 95% CI 0.98-1.05).
      CONCLUSION: Changes in lipid levels with hormone therapy are not predictive of
      CHD outcomes in women with heart disease in the HERS trial.

PMID- 14597938
TI  - Statin use is associated with enhanced collateralization of severely diseased
      coronary arteries.
AB  - BACKGROUND: The presence of coronary collateral vessels has been associated with
      improved clinical outcome in patients with coronary artery disease. Animal
      experiments have shown that hydroxymethyl glutaryl coenzyme A reductase
      inhibitors (statins) can promote angiogenesis in ischemic tissues in a
      cholesterol-independent manner. We hypothesized that statin therapy is associated
      with increased coronary collateral formation in patients with severe coronary
      artery disease. METHODS AND RESULTS: Patients undergoing clinically indicated
      coronary angiography at the Tufts-New England Medical Center from September 2000
      to April 2001 who had at least 1 major coronary artery occlusion, or a stenosis
      of > or =95% with Thrombolysis In Myocardial Infarction (TIMI) trial grade < or
      =1 anterograde flow on their angiograms, were included. Fifty-one patients were
      taking statins before admission, and 43 patients were not. Their angiograms were
      reviewed and coronary collaterals were graded from 0 to 3 according to the Cohen
      Rentrop method. The statin-treated group had a significantly higher mean
      collateral score compared with the patients not taking statins (2.05 vs 1.52, P
      =.005). Multivariate analysis supported the significance of the effect of statin
      therapy on the collateral score. There was no relation between collateral score
      and low-density lipoprotein levels (r = -0.06, P =.64). The statin-treated group
      also had a significantly higher left ventricular ejection fraction compared to
      the patients not taking statins (51% vs 44%, P <.05). CONCLUSIONS: Statin therapy
      is associated with enhanced coronary collateral formation in patients with
      severely diseased coronary arteries.

PMID- 14597939
TI  - Impact of lesion complexity on the capacity of a trial to detect differences in
      stent performance: results from the ISAR-STEREO trial.
AB  - BACKGROUND: A number of stent-versus-stent trials have not been able to disclose
      differences in stent performance. It has been hypothesized that the selection of
      patient subsets with simple lesion morphologies may have masked differences among
      the stent designs under testing. The randomized Intracoronary Stenting and
      Angiographic Results Strut Thickness Effect on Restenosis Outcome (ISAR-STEREO)
      trial has shown that a reduced stent strut thickness is associated with a reduced
      risk for restenosis. The rationale of this study was to investigate the role of
      lesion complexity on the capacity of a stent-versus-stent trial to distinguish
      between superior and inferior stents. METHODS: In the ISAR-STEREO trial, 651
      patients were randomly assigned to receive either a thin-strut (n = 326) or a
      thick-strut stent (n = 325) with a comparable stent design. Restenosis, defined
      as a > or =50% diameter stenosis at follow-up angiography, was analyzed according
      to the lesion complexity, which was assessed with the use of the American College
      of Cardiology/American Heart Association classification system. RESULTS: The
      restenosis rate did not differ between stent designs in patients with noncomplex
      lesions (type A or B(1); restenosis rate: 16.7% vs 16.7%, P = 1.0 for thin-strut
      vs thick-strut stents). In patients with complex lesions (type B2 or C), there
      was a significant reduction in restenosis in the thin-strut stent group
      (restenosis rate: 14.5% vs 29.0%; P <.01 for thin-strut vs thick-strut stents).
      CONCLUSIONS: The results of this study suggest that the potential to detect
      differences in the risk for restenosis in stent-versus-stent trials is strongly
      dependent on the inclusion of patients with complex lesions. These findings may
      be relevant when planning new stent-versus-stent trials.

PMID- 14597940
TI  - Death in patients with permanent pacemakers for sick sinus syndrome.
AB  - BACKGROUND: Although more than one million patients in the United States have
      permanent pacemakers, little is known about their cause of death. We evaluated
      the cause of death in 404 patients who died in the Mode Selection Trial (MOST).
      METHODS: In MOST, patients received a dual-chamber pacemaker randomly programmed
      to either dual-chamber or ventricular pacing. The circumstances surrounding each
      death were reviewed by a clinical events committee, which used prospectively
      defined criteria to adjudicate the cause of death. RESULTS: A total of 2010
      patients with a median age of 74 years were included. After a median follow-up of
      33 months, 404 (20%) patients died, including 198 (49%) of noncardiac causes and
      143 (35.4%) of cardiac causes. In 63 patients, the cause of death was unknown.
      Independent predictors of death through the use of a multivariable analysis were
      (1) demographic factors including age, male sex, and weight; (2) clinical factors
      including prior myocardial infarction, cardiomyopathy, New York Heart Association
      class III/IV, and the Charlson Comorbidity Index; and (3) scores from two
      measures of functional status, the Karnofsky Score and the Mini-Mental State
      Examination. Independent predictors of cardiovascular death were similar.
      CONCLUSIONS: Patients treated with permanent pacemakers for sinus node
      dysfunction are elderly and have a substantial mortality rate, with more than
      half the classifiable deaths being noncardiac. Baseline demographic variables and
      scores from quality-of-life measures can identify patients with the highest risk
      of death.

PMID- 14597941
TI  - Evaluation of the dofetilide risk-management program.
AB  - BACKGROUND: Dose-dependent torsades de pointes has been shown to occur with
      dofetilide (Tikosyn) and sotalol HCl (Betapace AF); thus, detailed dosing and
      monitoring recommendations to minimize this risk are included in the product
      labeling for both drugs. Only dofetilide, however, has a mandated risk-management
      program that restricts distribution of the drug and requires prescriber education
      on the drug. We investigated whether this program improved adherence to dosing
      and monitoring recommendations for dofetilide as compared with sotalol. METHODS:
      Charts for 47 patients taking dofetilide and 117 patients taking sotalol were
      reviewed. RESULTS: The recommended starting dose was prescribed more frequently
      in the dofetilide group than in the sotalol group (79% vs 35%, P <.001). A higher
      number of patients in the dofetilide group compared with the sotalol group
      received the recommended baseline tests for potassium (100% vs 82%, P <.001),
      magnesium (89% vs 38%, P <.001), serum creatinine (100% vs 82%, P <.001), and
      electrocardiography (94% vs 67%, P <.001). A significantly greater proportion of
      patients in the dofetilide group received recommended electrocardiograms obtained
      after the first dose (94% for dofetilide vs 43% for sotalol, P <.001) and
      subsequent doses (80% for dofetilide vs 3.5% for sotalol, P <.001). CONCLUSION:
      Better adherence to several dosing and monitoring recommendations in the
      dofetilide group may be caused by the presence of the risk-management program.
      However, low usage of dofetilide during the study period may signify an
      unintended, negative consequence of the risk-management program.

PMID- 14597942
TI  - Circadian variation of arrhythmia onset patterns in patients with persistent
      atrial fibrillation.
AB  - BACKGROUND: The circadian onset patterns and cycle lengths of atrial
      tachyarrhythmias (AT) were determined in a group of patients with persistent
      atrial fibrillation. METHODS: Fifteen patients, mean age 63 +/- 14 years and 80%
      male, were implanted with the Jewel AF atrial defibrillator (Medtronic,
      Minneapolis, Minn) for persistent atrial fibrillation only. Onset times of AT and
      median onset atrial cycle lengths were determined from device memory. RESULTS:
      Over a follow-up period of 23.3 +/- 7 months, 227 episodes of persistent AT were
      treated by patient-activated atrial defibrillation. The peak onset of persistent
      AT was nocturnal, with 74% of episodes initiating between 8 pm and 8 am. Eighty
      seven percent of the patients experienced an additional 403 paroxysmal AT
      episodes. These episodes showed a "double-peaked" pattern with the least number
      of episodes occurring between midnight and 8 am. The mean onset atrial cycle
      length of persistent AT was significantly shorter than the paroxysmal AT episodes
      (200 +/- 37 ms vs 240 +/- 39 ms, P <.005). The atrial cycle lengths at arrhythmia
      onset of both paroxysmal and persistent AT episodes also demonstrated circadian
      variation. CONCLUSION: There is a circadian distribution of onsets for persistent
      AT with predominance at night. Patients with persistent AF have >1 type of atrial
      arrhythmia with differences in the onset patterns and atrial cycle lengths,
      suggesting different triggers and onset mechanisms.

PMID- 14597943
TI  - Pacemaker therapy in very elderly patients: long-term survival and prognostic
      parameters.
AB  - BACKGROUND: Permanent pacing is the therapy of choice for treating severe and/or
      symptomatic bradyarrhythmia. However, augmented life expectancy and increasing
      health care expenditures have led to questions concerning the routine use of
      electrotherapy in very elderly patients. This study is aimed at assessing data on
      the actual number, characteristics, and survival of patients requiring pacing
      therapy at age > or =80 years. METHODS: Between 1971 and 2000, 1588 patients aged
      > or =80 years completed a standardized 6- to 12-month follow-up after pacemaker
      (PM) implantation, resulting in a total of 5244 patient years. Kaplan-Meier
      analyses were computed to visualize survival differences in various subgroups and
      implantation periods. RESULTS: Today, patients aged > or =80 years account for
      32% of all PM implantations. An increasing 5-year survival after PM implantation
      to the current rate of 66% was found, compared to 37% and 47% in the previous
      decades. Based on a mean survival time of 8 years, clinical symptoms can be
      effectively treated with costs of < or =500 dollars per patient per year.
      Prognostic parameters were the decade of implantation (relative risk [RR] 0.80,
      CI 0.67-0.96, P < or =.02), a history of presyncope (RR 0.73, CI 0.57-0.95, P <
      or =.02), and male sex (RR 1.20, CI 1.04-1.40, P < or =.02). However, none of
      these parameters can be recommended for estimating outcome or for guiding device
      selection. CONCLUSIONS: Patients aged > or =80 years account for an increasing
      portion of PM implantations. Considering the remaining life expectancy of 8 years
      in these patients, PM therapy is a clinically and economically effective
      therapeutic option to control bradyarrhythmia-related symptoms.

PMID- 14597944
TI  - False-positive exercise echocardiograms: impact of sex and blood pressure
      response.
AB  - BACKGROUND: Factors related to false-positive results of exercise
      echocardiography (ExE) to diagnose coronary disease have not been extensively
      studied. In addition, previous studies were performed before routine use of
      digital and tissue harmonic imaging. We evaluated the clinical and
      echocardiographic predictors of false-positive results during ExE. METHODS: Four
      hundred sixty-four patients who had both coronary angiography and ExE were
      enrolled retrospectively. Significant coronary disease was defined by stenoses >
      or =50% lumen diameter. RESULTS: Fifty-eight (13%) had false-positive results.
      Thirty-one (53%) of these patients were women, which was significantly higher
      than the percentage of women (25%) in the true-positive group (P <.001). Average
      peak systolic blood pressure (BP) in the false-positive group was significantly
      higher than in the true-positive group. Test specificity was decreased at higher
      levels of BP without change of sensitivity. Men demonstrated a decrease in
      specificity at peak systolic BP > or =200 mm Hg, whereas women showed a sharp
      decrease in specificity at BP > or =180 mm Hg. Wall motion score index (WMSI)
      after peak exercise and the proportion of high- and intermediate-risk patients
      according to Duke score were significantly lower in the false-positive than in
      the true-positive group. CONCLUSIONS: The factors predictive of false-positive
      results during ExE to diagnose coronary disease were female sex, higher BP at
      peak exercise, lower risk by Duke score and lower number of abnormal segments and
      wall motion score index after peak exercise. Women appear to be susceptible to
      wall motion abnormalities caused by elevated exercise BP. These variables should
      be considered in the interpretation of ExE.

PMID- 14597945
TI  - Self- and balloon-expandable stent implantation for severe native coarctation of
      aorta in adults.
AB  - BACKGROUND: Balloon angioplasty for native coarctation of the aorta (CoA) in
      adults, though promising, is sometimes limited by significant residual gradient
      (>20 mm Hg). Few studies available have reported on use of balloon-expandable
      stents in such a situation. We evaluated the use of self- and balloon-expandable
      stents in patients with suboptimal response to balloon angioplasty (BA). METHODS:
      Twenty-one hypertensive patients (age, 18 to 61 years; mean, 28.6 +/- 11.2 years)
      with native CoA and in whom results of BA were suboptimal (ie, residual peak
      systolic gradient [PSG] >20 mm Hg) underwent stent implantation. Balloon
      expandable Palmaz stents were implanted in 5 patients (group A) and self
      expandable nitinol aortic stents in the remaining 16 patients (group B). RESULTS:
      In group A, PSG decreased from 62.8 +/- 10.6 (53 to 80) mm Hg to 28.1 +/- 6.3 (22
      to 39) mm Hg after BA. Systolic gradient further decreased to 8.3 +/- 3.9 (2 to
      16) mm Hg (P <.001) after implantation of the balloon-expandable Palmaz stent. In
      group B, PSG decreased from 70.2 +/- 24.6 (40 to 110) mm Hg to 28.4 +/- 9.8 (22
      to 42) mm Hg after BA and further reduced to 9.0 +/- 5.5 (4 to 16) mm Hg (P
      <.001). One of these patients had a nitinol self-expandable stent implanted after
      a Palmaz stent embolized immediately after deployment. Nitinol stents were easier
      to deploy and conformed better to aortic anatomy compared with balloon-expandable
      stents. In group A, the diameter of the coarcted segment increased from 3.8 +/-
      0.8 mm to 13.3 +/- 0.8 mm (P <.001) after stent implantation and in group B it
      increased from 4.5 +/- 1.1 mm to 14.1 +/- 2.1 mm (P <.001). There was no
      significant difference between the two groups in the PSG and diameter of the
      coarcted segment before and after stent implantation. With the exception of one
      case, in which a Palmaz stent embolized, there was no other complication in our
      series. On follow-up of 12 to 71 months (mean, 40.7 +/- 5.8 months) all the
      implanted stents remained in their original position and none showed evidence of
      fracture. Improvement in hypertension was seen in 20 of 21(95.2%) of the
      patients. On recatheterization and angiography 1.2 +/- 0.6 years after
      implantation in 19 patients, one patient showed an increase in PSG to 27 mm Hg
      across the nitinol stent and underwent successful redilation. No increase in
      gradient was seen in other patients. Beneficial late remodeling was seen in 10 of
      14(71.4%) of patients restudied after implantation of self-expandable stent. None
      of the patients showed aneurysm formation. CONCLUSIONS: Stent implantation is
      safe and effective in improving suboptimal results after BA for CoA. Self
      expandable stents were easier to implant, adapted better to the wall of the
      aorta, and in most patients had similar efficacy in reducing coarctation as
      balloon-expandable stents.

PMID- 14597946
TI  - Comparison of the effect of valsartan and lisinopril on autonomic nervous system
      activity in chronic heart failure.
AB  - BACKGROUND: In chronic heart failure (CHF), the derangement of autonomic nervous
      system activity has a deep impact on the progression of the disease. It has been
      demonstrated that modulation of the renin-angiotensin aldosterone system (RAAS)
      increases autonomic control of heart rate and reduces adrenergic activity. We
      sought to evaluate, in CHF, the different effects of an ACE inhibitor
      (lisinopril) and of an AT1 receptor antagonist (valsartan) on heart rate
      variability, baroreflex sensitivity and norepinephrine plasma levels. METHODS:
      Ninety patients (61 +/- 10 years, 2.3 +/- 0.5, New York Heart Association class)
      with CHF and left ventricular ejection fraction <40% were randomly assigned in a
      double-blind fashion to receive lisinopril (uptitrated to 20 mg/d) or valsartan
      (uptitrated to 160 mg/d) therapy for 16 weeks. Heart rate variability (evaluated
      by measuring standard deviation of normal R-R intervals on 24-hour ECG
      recordings), spontaneous baroreflex sensitivity and aldosterone and
      norepinephrine plasma levels were assessed before and after drug therapy.
      RESULTS: There were no significant differences between valsartan and lisinopril
      in their effects on left ventricular function, arterial pressure, aldosterone
      plasma levels and autonomic control of heart rate. Both lisinopril and valsartan
      significantly reduced plasma norepinephrine levels, but the reduction induced by
      valsartan was significantly greater than that observed for lisinopril (27% vs 6%,
      P <.05). CONCLUSIONS: This study shows a comparable effect of ACE inhibition
      (lisinopril) and of AT1 receptor antagonism (valsartan) on cardiac vagal control
      of heart rate, whereas valsartan has shown a more effective modulation of
      sympathetic activity measured by plasma norepinephrine levels.

PMID- 14597947
TI  - Short- and long-term beneficial effects of trimetazidine in patients with
      diabetes and ischemic cardiomyopathy.
AB  - BACKGROUND: Trimetazidine (TMZ) has been shown to partially inhibit free fatty
      acid oxidation by shifting substrate utilization from fatty acid to glucose. The
      aim of this study was to assess the effects of TMZ in patients with diabetes and
      ischemic cardiomyopathy. METHODS: Sixteen patients with diabetes and ischemic
      hypokinetic cardiomyopathy (all males) on conventional therapy were randomized to
      receive either placebo or TMZ (20 mg 3 times per day), each arm lasting 15 days,
      and then again to receive either placebo or TMZ for 2 additional 6-month periods,
      according to a double-blind, crossover design. At the end of each period, all
      patients underwent exercise testing, 2-dimensional echocardiography, and
      hyperinsulinemic/euglycemic clamp. Among the others, New York Heart Association
      class, ejection fraction, exercise time, fasting blood glucose, end-clamp M value
      (index of total body glucose disposal) and endothelin-1 levels were evaluated.
      RESULTS: Both in the short and long term (completed by 13 patients), on TMZ
      compared to placebo, ejection fraction (47 +/- 7 vs 41 +/- 9 and 45 +/- 8 vs 36
      +/- 8%, P <.001 for both) and M value (4.0 +/- 1.8 vs 3.3 +/- 1.6, P =.003, and
      3.5 +/- 1.5 vs 2.7 +/- 1.6 mg/kg body weight/min, P <.01) increased, while
      fasting blood glucose (121 +/- 30 vs 136 +/- 40, P =.02 and 125 +/- 36 vs 140 +/-
      43, P =.19) and endothelin-1 (8.8 +/- 3.8 vs 10.9 +/- 3.8, P <.001 and 6.2 +/-
      2.4 vs 9.2 +/- 4.3 pg/mL, P =.03) decreased. In the short term, 10 patients
      decreased 1 class on the NYHA scale during treatment with TMZ (P =.019 vs
      placebo). Eight patients decreased 1 NYHA class while on long-term TMZ treatment,
      while on placebo 1 patient increased 1 NYHA class and none improved (P =.018 vs
      placebo). CONCLUSIONS: In a short series of patients with diabetes and ischemic
      cardiomyopathy, TMZ improved left ventricular function, symptoms, glucose
      metabolism, and endothelial function. Shifting energy substrate preference away
      from fatty acid metabolism and toward glucose metabolism by TMZ appears an
      effective adjunctive treatment in patients with diabetes with postischemic
      cardiomyopathy.

PMID- 14597948
TI  - Effects of 2 different antiplatelet regimens with abciximab or tirofiban on
      platelet function in patients undergoing coronary stenting.
AB  - BACKGROUND: We sought to compare the antiplatelet effects of the glycoprotein IIb
      IIIa receptor blockers abciximab or tirofiban, combined with an adjuvant therapy
      with clopidogrel and aspirin. STUDY DESIGN AND METHODS: Twenty patients
      undergoing coronary stenting were randomly assigned to receive either abciximab
      or tirofiban combined with aspirin and clopidogrel. Serial blood samples were
      taken to assess platelet aggregation, P-selectin expression, thrombin generation,
      and platelet-induced endothelial cell expression of MCP-1, uPAR, and ICAM-1.
      Results and conclusions The therapy with aspirin plus clopidogrel attenuated
      agonist-induced platelet aggregation and P-selectin surface exposure (P <.05 vs
      aspirin monotherapy). Both tirofiban and abciximab further reduced agonist
      induced platelet aggregation (P <.05), and decreased thrombin generation but had
      no effect on platelet alpha-granule release. None of the antithrombotic
      strategies significantly affected platelet-induced endothelial cell activation.
      Since platelet adhesion/degranulation initiates an inflammatory/mitogenic
      response in the vascular wall, future therapeutic strategies will have to be
      aimed at the inhibition of platelet release reactions.

PMID- 14597949
TI  - [Prediction of postoperative complications in elective surgery].
AB  - Experience in prediction of surgical outcomes is summarized. Preliminary results
      of elective treatment of various surgical diseases are reviewed. Over the last 14
      years some theoretical problems of prediction (surgical risk) were solved by the
      authors and decision making in critical situations is illustrated. Surgical
      outcomes in 500 patients operated on from 1972 to 2002 (30 years) were analyzed
      depending on a number of factors--age, severity of combined diseases and surgery
      traumaticity. It is noted that qualitative assessment of surgical risk is not
      enough for decision on the method of surgical treatment. It is necessary to
      create adequate and simple classification of criteria of postoperative prognosis
      in elective surgery able to realize quantitative assessment of surgical risk.

PMID- 14597950
TI  - [Surgical treatment of thymomas in patients with generalized myasthenia gravis].
AB  - Experience in surgical treatment of 2977 patients with generalized myasthenia is
      presented, 386 (13%) of them have undergone surgeries for thymus tumors. Organo
      specific tumors (thymoma) were diagnosed in 370 (95.9%) of them. Computed and
      magnetic-resonance tomography has the highest sensitivity and specificity in
      diagnosis of thymus tumors. Thymomthymectomy was performed in 317 patients
      including extended one in 117 (36.9%). Postoperative lethality in thymic tumor in
      the last years was 0.5%, general lethality over all period--5.1%. According to
      used classification (WHO, 1999) types of thymoma were the following: type A-
      2.1%, type B--86.3%, type AB--9.6%. Prognosis of surgical treatment depends of
      tumor type (it is worse in type B than in types A and AB), duration of the
      disease and severity of myasthenia.

PMID- 14597951
TI  - [Assessment of efficacy of endarterectomy of coronary arteries].
AB  - Results of coronary artery bypass grafting (CABG) with coronary endarterectomy
      (CE) are analyzed. The study group consisted of 97 patients who has undergone ACB
      with CE, control group--102 patients after ACB without CE. There were no
      differences in clinical state of the patients early (30 days) and late (1-2
      years) after surgery. Computed tomography was used for detection of coronary
      bypass patency. In long-term period of follow-up (60 patients) autoarterial
      shunts were occluded in 3% cases in the study group and in 5% cases in the
      control one. Autovenous shunts were occluded in 36 and 27% cases respectively.
      These results demonstrate necessity of CE in CABG.

PMID- 14597952
TI  - [Instrumental diagnosis of reflux esophagitis].
AB  - One hundred and forty patients with clinical symptoms of gastroesophageal reflux
      disease were examined. Instrumental examination included
      esophagogastroduodenoscopy (140 patients) with target biopsy (44 patients), x-ray
      study of the esophagus and stomach (95), intragastric pH-metry (74),
      esophagomanometry (67). It is demonstrated that all the patients with clinical
      picture of gastroesophageal reflux disease suffer from reflux-esophagitis (RE) of
      various severity. Definite morphological equivalents correspond to each of
      endoscopic forms of RE. Complex instrumental diagnosis of RE must include
      intragastric pH-metry and esophagomanometry in line with
      esophagogastroduodenoscopy and morphological study. It is necessary to perform x
      ray study in peptic strictures of the esophagus and in combination of RE with
      large axial hiatal hernias. Cardial or cardial-fundal hiatal hernia, increase of
      intragastric pressure and hyperacidity promote development of the most severe
      (destructive) forms of RE.

PMID- 14597953
TI  - [Endoscopic radio wave hemostasis in combined treatment of gastroduodenal ulcers
      complicated by bleeding].
AB  - Radiowave hemostasis was used for endoscopic stopping of bleeding from gastric
      and duodenal ulcers in 96 patients. Primary single radiowave hemostasis permitted
      to achieve stable effect in 80 (83.3%) patients. After repeated radiowave
      hemostasis bleeding was completely stopped in 14 (14.6%) patients, 2 (2.1%)
      patients of this group underwent urgent surgery. On day 10 after radiowave
      hemostasis 95% of mucosal defects epithialized.

PMID- 14597954
TI  - [Endoscopic treatment of bleeding due to Mallory-Weiss syndrome].
AB  - Experience in diagnosis and treatment of 276 patients with Mallory--Weiss
      syndrome (MWS) is presented. Definition of the syndrome and brief historical
      review (from first description of disruption of esophageal-gastric connection to
      first report of successful hemostasis through endoscope) are given. Particular
      attention is devoted to etiology and pathogenesis of this syndrome. Clinical
      material and picture of disease, results of endoscopic diagnosis are analyzed,
      efficacy of endoscopic hemostasis and prophylaxis of hemorrhage is demonstrated.
      Indications to various methods of endoscopic hemostasis are regarded, results of
      treatment and lethal outcomes are analyzed. It is demonstrated that endoscopic
      procedures are the method of choice in the treatment of this disease reducing
      emergency surgery rate to 0.4%.

PMID- 14597955
TI  - [Treatment of calculous cholecystitis and its complications].
AB  - Results of treatment of 10,724 patients with different forms of acute and chronic
      cholecystitis are analyzed. Surgical treatment was performed in 7819 (72.9%)
      patients. Variants of treatment of acute and chronic cholecystitis are presented.
      Typical cholecystectomy is the basic surgery in patients with acute calculous
      cholecystitis (63% procedures). Laparoscopic cholecystectomy (LCE) was performed
      in 37% patients. Two-stage surgeries with previous microcholecystostomy (MCS) and
      endoscopic papilloshincterotomy (EPST) are indicated in late hospitalization of
      patients with intoxication and severe concomitant diseases. They permit to
      prepare patients for cholecystectomy and to decrease scope of surgery. In
      cholelithiasis and jaundice EPST and MCS are indicated for almost all patients as
      a preliminary procedure before surgery on the biliary tract and cholecystectomy.
      This two-stage variant permitted to reduce postoperative lethality from 9.7 to
      1.6%. In chronic cholecystitis LCE is the main type of surgery with minimal
      postoperative lethality. For patients with recurrent calculous cholecystitis,
      frequent exacerbations, severe concomitant diseases EPST in choledocholithiasis
      and sanation of gall bladder through fistula are indicated.

PMID- 14597957
TI  - [Early diagnosis of intra-abdominal complications after surgery on the stomach
      and the duodenum].
AB  - Ultrasonic examination early after surgery permits to visualize "zone of
      surgery", to evaluate stomach, duodenum or their stump, to diagnose motor
      evacuatory and purulent-septic complications, to determine policy of their
      treatment. Dynamic ultrasonic examinations permit to realize daily monitoring of
      "surgical zone" and timely correction of therapy, to reduce number of x-ray and
      endoscopic examinations after surgery that leads to improving of treatment
      results.

PMID- 14597956
TI  - [Results of suturing of esophageal and gastric varicose veins in patients with
      extrahepatic portal hypertension].
AB  - Experience in gastrectomy with suturing of varicose veins (VV) of the esophagus
      and stomach (M.D. Patsiora's surgery) in 349 patients with extrahepatic portal
      hypertension (EPH) is reviewed. Short and long-term results of this surgery
      through abdominal and transthoracal approach are analyzed. Postoperative
      lethality in patients with EPH after elective surgery was 5.0%, urgent surgery-
      16%. Recurrence of esophagogastric bleeding in postoperative period was seen in
      23 (6.6%) patients. 286 patients were followed up from 1 to 10 years. Recurrence
      of esophageal-gastric bleeding was seen in 104 (36.4%) patients and led to death
      in 19 (18.3%) of them. It is concluded that suturing of esophageal and gastric VV
      in patients with EPH is a method of choice both in prolonged bleeding and as
      preventive elective surgery when creation of vascular anastomosis is impossible.

PMID- 14597958
TI  - [Transanal endoscopic surgical method of removing rectal tumors].
AB  - Experience in endosurgical removal of rectal tumors in 96 patients is presented.
      Performed from 1999, open non-gas method and closed method of transanal
      endomicrosurgery (TEM) have reduced rate of adenoma recurrences to 8.8%.
      Development of the open method increased it accessibility for hospitals using
      endoscopic techniques.

PMID- 14597959
TI  - [Diseases of fatty appendices of the colon].
AB  - Seventy-one patients with volvulus of fatty appendix of the colon (sigmoid colon-
      52 patients, caecum--12, ascending colon--5, vermicular appendix--2 patients)
      were treated. Volvulus of epiploic appendix was seen in 67.6% operated patients,
      inflammatory changes--in 28.1% (primary inflammation was diagnosed in 4.2%
      patients). Symptoms of fat metabolism disorders were detected in 44 patients.
      There are no specific symptoms. Diagnostic laparoscopy permitted to improve
      diagnosis of epiploic appendices diseases. Target surgical approach permitted to
      reduce rate of postoperative complications and to improve results of treatment.

PMID- 14597960
TI  - [Target thin-needle puncture biopsy in diagnosis of thyroid cancer].
AB  - One hundred medical histories of patients with thyroid cancer (TC) were analyzed.
      Patients were divided into two groups depending on the variant of thin-needle
      biopsy technique (TNB). In group 1TNB was performed with "blind" method (with
      palpation control)--43 cases, in group 2 target TNB (ultrasound-guided) was
      carried out--57 cases. Patients of each group were divided depending on
      cytological presurgical diagnosis. Statistical analysis was carried out with two
      sided Fisher's criterion. It is demonstrated that detection of TC in group 2
      (84.2%) was higher than in group 1 (62.8%) where "blind" method of puncture was
      used (p = 0.020). It is recommended to perform target TNB in all cases of nodular
      goiter that improves quality of TC diagnosis.

PMID- 14597961
TI  - [Regional circulation in gunshot wounds of the ankle joint and foot].
AB  - Problems of treatment of battle injuries of the ankle joint and foot are
      discussed. These injuries are characterized with severe disturbances of regional
      circulation and microcirculation causing hypoxia and metabolic disorders both in
      soft tissues and in bones. Digital substraction angiography (DSA) was used in 7
      wounded (7.53%) of all patients with battle injuries of the foot and ankle joint.
      Combined treatment including surgery, drugs, physical and exercise therapy,
      hyperbaric oxygenation was used in all the patients. Prolonged intraarterial
      infusion of drugs was carried out in 4 of 7 patients. It is concluded that early
      evaluation of regional circulation permits to clarify expediency of applied
      combined treatment. Injury of three arteries is the indication for amputation,
      but even one functioning artery enables use of combined therapy with
      intraarterial infusion for extremity salvage.

PMID- 14597962
TI  - Making sense of microarray data to classify cancer.

PMID- 14597963
TI  - Influence of CYP2C9 genotypes on the formation of a hepatotoxic metabolite of
      valproic acid in human liver microsomes.
AB  - The present study investigated the effect of cytochrome P450 2C9 (CYP2C9) genetic
      polymorphism on the biotransformation of valproic acid (VPA) to its hepatotoxic
      metabolite, 4-ene-VPA, and compared that to the formation of the inactive 4-OH
      VPA and 5-OH-VPA. cDNA-expressed CYP2C9(*)2 and CYP2C9(*)3 variants were less
      efficient than the CYP2C9(*)1 wild type in catalyzing the formation of these
      metabolites, as assessed by the ratio of Vmax and apparent Km (in vitro intrinsic
      clearance). The reduced efficiency by CYP2C9(*)2 was due to a reduced Vmax,
      whereas, in the case of CYP2C9(*)3, it was the result of increased apparent Km.
      The formation rates of 4-ene-VPA, 4-OH-VPA, and 5-OH-VPA in human liver
      microsomes were reduced by 29, 28, and 31%, respectively, in samples with one
      mutated CYP2C9 allele, and by 61, 73, and 58%, respectively, in samples with two
      mutated CYP2C9 alleles. Overall, the homozygote and heterozygote CYP2C9(*)2 and
      CYP2C9(*)3 genotypes may compromise hepatic VPA biotransformation.

PMID- 14597964
TI  - The uncertain nature of dopamine.

PMID- 14597965
TI  - Thrombin generation: old wine into new wineskins.

PMID- 14597966
TI  - Insertion/deletion polymorphism of the angiotensin-converting enzyme gene: really
      a risk factor for venous thromboembolism?

PMID- 14597967
TI  - Factor VIII and race: a new dimension in hypercoagulability.

PMID- 14597968
TI  - Extending knowledge on inherited platelet disorders associated with
      thrombocytopenia.

PMID- 14597969
TI  - Up and down with PARs in vivo.

PMID- 14597970
TI  - Animal models of vulnerable plaque. Clinical context and current status.
AB  - There is increasing recognition of the importance of vulnerable plaque and acute
      plaque rupture leading to thrombosis, in the pathogenesis of acute coronary
      syndromes. This is fueling a number of developments, including novel imaging
      modalities and potential plaque stabilization therapies. However, to date, no
      animal model of vulnerable plaque or plaque rupture has been established. Recent
      developments, particularly using Apo E knockout mice, appear set to provide key
      breakthroughs. The present status of our understanding of plaque vulnerability is
      therefore discussed, with a discussion of these current advances in animal
      models.

PMID- 14597971
TI  - Thrombin generation in severe haemophilia A and B: the endogenous thrombin
      potential in platelet-rich plasma.
AB  - Thrombin generation was investigated in platelet-rich plasma (PRP) from 11
      healthy controls, 17 patients with severe haemophilia A and 7 patients with
      severe haemophilia B. Mean endogenous thrombin potential (ETP) in arbitrary
      fluorescence units (FU) was 226.9 +/- 44.6, 186.4 +/- 22.5, 154.2 +/- 41.3 in
      controls, haemophilia A and B, respectively, all at a platelet count of 200 x
      10(9)/l (p = 0.004 for controls vs. haemophilia A, p = 0.003 for controls vs.
      haemophilia B, no significant difference between haemophilia A and B). The
      contribution of FVIII to thrombin generation in haemophilia A was 1.31 +/- 0.16
      FU/% of FVIII:C activity, while for FIX in haemophilia B this was 0.80 +/- 0.21
      FU/% of FIX activity. There was an almost linear relationship between increasing
      platelet count and thrombin generation up to a mean platelet count of 100 x
      10(9)/l. Further increase in platelet count has only a marginal influence on
      thrombin generation. Platelets increase ETP in haemophilia A by 0.184 +/- 0.022
      FU/10(9) platelets/l and in haemophilia B by 0.319 +/- 0.085 FU/10(9)
      platelets/l, and this was significantly different between the two groups (p =
      0.0002). This influence of plate-lets diminishes with increasing concentration of
      either FVIII or FIX. In conclusion, there is a difference in thrombin generation
      between haemophilia A and B, and this may be attributed to the role of platelets
      in the assembly of the tenase complex on their surface.

PMID- 14597973
TI  - Intracoronary beta2 receptor activation induces dynamic local t-PA release in the
      pig.
AB  - To investigate beta2 -adrenergic agonist-mediated effects on coronary fluxes of
      local fibrinolytic factors, healthy anaesthetised and instrumented pigs (n=10)
      were studied during infusion of isoprenaline (IPR) into the left main coronary
      artery. Coronary net fluxes of total t-PA antigen, active t-PA and total PAI-1
      antigen were determined at baseline and at 3, 5, 7 and 10 minutes of IPR
      infusion. During IPR, net release of total t-PA increased in a biphasic pattern
      with transiently high levels at 3 (+440 %) and 7 minutes (+620%) and returned
      towards baseline at 10 minutes. Net coronary release of active t-PA increased
      with maximum levels at 3 minutes (+50%). Baseline coronary net flux of total PAI 
      1 showed a decrease which was most pronounced at 10 minutes. To conclude, a fast
      beta2 agonist-mediated local release of t-PA into the coronary vasculature was
      demonstrated. For total t-PA, this response was characterised by a biphasic
      release profile.

PMID- 14597972
TI  - High molecular weight kininogen and factor XII binding to endothelial cells and
      astrocytes.
AB  - We have quantitated the binding of high molecular weight kininogen (HK) to human
      microvascular endothelial cells of lung and dermal origin as well as to
      astrocytes and compared the results with those reported for human umbilical vein
      endothelial cells (HUVEC). We also reassessed parameters of binding to HUVEC
      employing cells in suspension as well as cells attached to the culture plate and
      report similar numbers of sites varying from 6.96x10(5) to 7.71x10(5) per cell.
      The present study shows that HK binds with high specificity and affinity to
      microvascular endothelial cells (Kd = 1.86 to 4.5 nM) compared to HUVEC (Kd =
      10.35 nM) but with lower affinity to astrocytes (Kd = 23.73 nM). Human
      cytokeratin 1, urokinase plasminogen activator receptor and gC1qR were found to
      be HK binding proteins present at the surface of microvascular endothelial cells
      and astrocytes analogous to that seen in HUVEC, as assessed by inhibition of
      binding with antibody to each protein. Lung microvascular endothelial cells had
      approximately half the number of HK binding sites as HUVEC while dermal micro
      vascular endothelial cells and astrocytes had only 8-10% of the sites/cell. The
      affinity of binding to the microvascular endothelial cells was greater than
      HUVEC, the affinity of binding to astrocytes was considerably less, nevertheless
      binding to each cell type involves gC1qR, cytokeratin 1 and u-PAR to varying
      degrees. We also demonstrate, for the first time, that factor XII binds to all of
      these cell types in a saturable and Zn(+2) dependent manner. Given that factor
      XII accelerates the interactions among cell surfaces and proteins of the contact
      activation cascade to generate bradykinin, binding of factor XII (and the
      prekallikrein-HK complex) may serve as a mechanism by which these proteins are
      concentrated locally to facilitate their interactions.

PMID- 14597974
TI  - Pharmacokinetics and anticoagulant properties of the factor VIIa-tissue factor
      inhibitor recombinant Nematode Anticoagulant Protein c2 following subcutaneous
      administration in man. Dependence on the stoichiometric binding to circulating
      factor X.
AB  - Recombinant Nematode Anticoagulant Protein c2 (rNAPc2) is a potent (K(i) =10 pM),
      inhibitor of the factor VIIa/tissue factor (fVIIa/TF) complex that requires the
      prerequisite binding to zymogen or activated factor X (fX). In two double blind,
      place-bo-controlled, sequential dose-escalation phase I studies, rNAPc2 was found
      to be safe and well tolerated following single and repeat subcutaneous
      administrations in healthy human male volunteers at doses ranging from 0.3 to 5
      micro g/kg. There was a dose-dependent elevation of the prothrombin time reaching
      almost 4-fold above the baseline value in the highest dose group that directly
      correlated with rNAPc2 plasma concentration. In contrast, there was little or no
      effect on the activated partial thromboplastin time, thrombin time or template
      bleeding time. The pharmacokinetic behavior of rNAPc2 revealed a dose-independent
      and prolonged elimination half-life (t(1/2)beta) with a mean of >50 hours. A high
      affinity interaction between rNAPc2 and plasma fX was shown to be essential for
      the prolonged t(1/2)beta in man using crossed immunoelectrophoresis and was
      confirmed by exploiting the considerably weaker interaction between rNAPc2 and
      bovine fX which resulted in an attenuated t(1/2)beta of approximately 1.5 hours
      in calves. The accumulated data suggests that rNAPc2 is safe and well tolerated
      following repeat subcutaneous administrations at doses up to 5 micro g/kg in
      healthy volunteers. In addition, the in vivo fate of rNAPc2 in man appears to be
      governed by its high affinity interaction with circulating fX. This data supports
      the continued development of this novel anticoagulant for the prevention and
      treatment of acute thrombotic disorders.

PMID- 14597975
TI  - Restricted BV gene usage by factor VIII-reactive CD4+ T cells in inhibitor
      positive patients with severe hemophilia A.
AB  - In the present study, we have analyzed the T cell receptor (TCR) repertoires of
      CD4+ T cells isolated from peripheral blood of 10 inhibitor-positive patients
      with severe hemophilia A. The distribution of complementarity determining region
      (CDR3) lengths of the beta chain of the TCRs was analyzed by spectratyping prior
      to and following in vitro stimulation of the cells with human factor VIII
      (FVIII). The repertoires of CD4+ T cells of patients were perturbed when compared
      to those of healthy blood donors. The perturbations of T cell repertoires were
      heterogeneous among patients with respect to the number and the nature of V-beta
      (BV) families that exhibited expansion following incubation with FVIII. Some
      patients showed alterations in one or two BV families, others exhibited more
      perturbed repertoires affecting 5 to 8 of the 14 BV families tested. Alterations
      of BV2, BV5 and/or BV9 were consistently found after incubation of CD4+ T cells
      in the presence of FVIII in 80% of the patients. These findings indicate that the
      presence of FVIII inhibitors in patients with severe hemophilia A is associated
      with measurable perturbations of the CD4+ T cell repertoire that results from
      oligoclonal expansion of FVIII-specific cells and may be relevant for the design
      of strategies aimed at modulating the anti-FVIII immune responses by T cell
      targeted therapy

PMID- 14597976
TI  - Thrombophilia does not increase risk for neonatal complications in preterm
      infants.
AB  - The association between thrombophilia and neonatal complications was evaluated in
      a single-center prospective study. Prevalence of genetic prothrombotic markers
      (FVL, MTHFR, FIIG20210A) and levels of plasma homocysteine were assayed in 166
      premature (mean gestational age: 30.9+/-2.3 weeks) and low birth weight (mean
      weight: 1327+/-319 grams) infants. The incidence of any neonatal complications
      was compared in infants with and without thrombophilia. A total of 38 infants
      were defined as "thrombophilic" due to heterozygous FVL (n=4) and/or FIIG20210A
      (n=8, including one case of combination with FVL) or homozygous 677T MTHFR (n=22)
      or homocysteine plasma levels above 15 micro mole/liter. Neonatal complications
      included: small for gestational age (28.8%), respiratory distress syndrome
      (51.8%), broncho-pulmonary dysplasia (10.2%), patent ductus arteriosus (12.7%),
      intraventricular hemorrhage (17%), periventricular leucomalacia (8.4%),
      retinopathy of prematurity (15.1%) and necrotizing enterocolitis in 1.2% of
      infants. No thrombosis was documented. The prevalence of perinatal complications
      and the severity of diseases were similar among infants with or without
      thrombophilia (p = 0.564). Our data suggest that preterm infants with
      thrombophilia are not at increased risk for developing neonatal complications.

PMID- 14597978
TI  - Risk factors for venous thrombosis in the black population.
AB  - Risk factors for venous thrombo-embolism (VTE) in the black population are poorly
      characterized. Of 142 black cases tested a genetic cause was identified in only
      9.1%: 4.2% had protein C deficiency, 2.8% protein S deficiency, 0.7% antithrombin
      deficiency and 1.4% were heterozygous for FV Leiden. We hypothesised that
      elevated factor VIII levels constitute a candidate risk factor for venous
      thrombosis in the black population. Factor VIII (FVIII:C) levels were determined
      in 100 black patients with VTE and 100 black controls in a case-control study. Of
      the patients 34% had a FVIII:C above 228 IU/dL (the 90th centile value in normal
      blacks) compared to 10% controls. Relative to those with FVIII:C below this
      value, odds ratio (OR) for risk of VTE was 4.64 (95% CI 2.02-10.85). When FVIII:C
      below 150 IU/dL was used as a comparator, OR was 11.1 (95% CI 4.29-29.43). There
      was evidence for a dose-response relationship. We propose that raised FVIII:C is
      a major risk factor for VTE in black subjects with prevalence and odds ratio
      exceeding those reported for white subjects.

PMID- 14597977
TI  - The ACE D/D genotype is protective against the development of idiopathic deep
      vein thrombosis and pulmonary embolism.
AB  - The deletion/deletion (D/D) genotype of the angiotensin converting enzyme (ACE)
      has been purported to be a risk for post-operative thrombosis.This D/D genotype
      has not been evaluated as a risk factor for idiopathic venous thromboembolism
      (VTE). The primary objective of the present study was to determine whether the
      D/D genotype of ACE is independently associated with the occurrence of idiopathic
      venous thromboembolic disease. We prospectively enrolled consecutive patients
      with at least one objectively confirmed idiopathic VTE. Friends of cases were
      recruited as controls and matched to cases by sex, ethnicity, and age. Patients
      were tested for the ACE I/D polymorphism in addition to factor V Leiden,
      prothrombin G20210A, and factor VIII levels. Three hundred cases and 300 controls
      were enrolled; 97% were Caucasian. There were 148 females and 152 males in each
      group with a mean age of 56.21 years (SD = 15.33). The ACE D/D genotype was
      present in 25.3% of cases and 32.4% of controls for an adjusted odds ratio of
      0.66 (95% CI = 0.433 to 0.997). We can conclude that the ACE D/D genotype is
      protective against idiopathic venous thromboembolism.

PMID- 14597979
TI  - The antiaggregating activity of clopidogrel is not affected by N-acetyl L
      cysteine.
AB  - N-acetyl L-cysteine (NAC) is widely used to treat obstructive bronchopulmonary
      diseases. It has thiol reactive properties, accounting for its mucolytic
      activity. Clopidogrel is a potent antithrombotic compound, metabolised by the
      liver which generates an active metabolite containing a thiol reactive group,
      responsible for an irreversible interaction with the platelet P2Y(12) ADP
      receptor. The aim of this study was to determine if NAC interferes with the
      antiaggregating activity of clopidogrel. For this purpose, NAC (100 micro M) was
      incubated with platelets from rats treated or not with clopidogrel (5 mg/kg, PO, 
      2 h). Clopidogrel treatment strongly inhibited aggregation but this effect was
      not modified by NAC. In another experiment, a low concentration of the active
      metabolite of clopidogrel (0.3 micro g/ml) was incubated with platelets from men
      or rats, in the absence or presence of NAC (100 micro M). When stimulated by ADP
      (2.5 micro M), platelet aggregation was inhibited by the active metabolite when
      incubated alone. In the presence of NAC, the inhibition by the active metabolite
      was not modified, therefore clearly indicating that NAC cannot reduce the thiol
      reactive part of the active metabolite of clopidogrel and does not interfere with
      its anti-aggregating activity. Moreover, in rats treated for 5 days with NAC (150
      mg/kg), the activity of clopidogrel (5 or 10 mg/kg) against ADP-induced platelet
      aggregation was neither inhibited nor increased. This demonstrates that the
      generation of the active metabolite of clopidogrel is not affected by NAC. In
      conclusion, we have found that NAC does not restore the "normal" properties of
      P2Y(12) on platelets from clopidogrel-treated animals, it does not interfere with
      the antiaggregating activity of the active metabolite of clopidogrel, and does
      not interfere with the generation of the active metabolite.

PMID- 14597980
TI  - Studies of alpha-granule proteins in cultured human megakaryocytes.
AB  - alpha-Granule protein storage is important for producing platelets with normal
      haemostatic function. The low to undetectable levels of several megakaryocyte
      synthesized alpha-granule proteins in normal plasma suggest megakaryocytes are
      important to sequester these proteins in vivo. alpha-Granule protein storage in
      vitro has been studied using other cell types, with differences observed in how
      some proteins are processed compared to platelets. Human megakaryocytes, cultured
      from cord blood CD34(+) cells and grown in serum-free media containing
      thrombopoietin, were investigated to determine if they could be used as a model
      for studying normal alpha-granule protein processing and storage. ELISA indicated
      that cultured megakaryocytes contained the alpha-granule proteins multimerin, von
      Willebrand factor, thrombospondin-1, beta-thromboglobulin and platelet factor 4,
      but no detectable fibrinogen and factor V. A significant proportion of the alpha
      granule protein in megakaryocyte cultures was contained within the cells
      (averages: 41-71 %), consistent with storage. Detailed analyses of multimerin and
      von Willebrand factor confirmed that alpha-granule proteins were processed to
      mature forms and were predominantly located in the alpha-granules of cultured
      megakaryocytes.Thrombopoietin-stimulated cultured megakaryocytes provide a useful
      model for studying alpha-granule protein processing and storage.

PMID- 14597981
TI  - A mutation in the integrin alphaIIb subunit that selectively inhibits alphaIIb
      beta3 receptor function.
AB  - The alpha(IIb) and alpha(v) integrins have been shown to play a significant role
      in a variety of disease processes. alpha(IIb)beta(3) is a platelet-specific
      fibrinogen receptor that is critical for thrombosis and hemostasis. Determination
      of the basis of ligand recognition by alpha(IIb)beta(3) is essential for
      modulation of platelet function. To identify alpha(IIb) residues involved in
      alpha(IIb)beta(3) ligand binding function, cells expressing a constitutively
      active variant of alpha(IIb)beta(3) were randomly mutagenized and selected for
      loss of alpha(IIb)beta(3) ligand binding function. One mutant isolated in this
      manner contained a single amino acid substitution at position 96 in alpha(IIb)
      (Ser9-->Leu). Cells expressing this alpha(IIb) mutant did not bind the ligand
      mimetic antibody PAC1 or adhere to fibrinogen. In addition, the mutant receptor
      did not bind to an RGD affinity matrix. Substitution of conserved serine residues
      at position 1 in beta strand A of all seven repeats of alpha(IIb) similarly
      inhibited ligand binding to alpha(IIb)beta(3). alpha(IIb)S96 maps to the central
      cavity of the beta-propeller fold of the alpha(IIb) subunit immediately adjacent
      to a structurally important sequence at the center of the alphaand beta subunit
      interface. In contrast, substitution of the analogous residues in alpha(v) or
      alpha(4) did not disrupt the ligand binding function of alpha(v)beta(3) or
      alpha(4)beta(1). These data support a potential unique structural or mechanistic
      role for this residue in alpha(IIb)beta(3) receptor function.

PMID- 14597982
TI  - AMP-activated protein kinase (AMPK) regulates the insulin-induced activation of
      the nitric oxide synthase in human platelets.
AB  - Little is known about the signaling cascades that eventually regulate the
      activity of the endothelial nitric oxide synthase (eNOS) in platelets. Here, we
      investigated the effects of insulin on the phosphorylation and activation of eNOS
      in washed human platelets and in endothelial cells. Insulin activated the protein
      kinase Akt in cultured endothelial cells and increased the phosphorylation of
      eNOS on Ser(1177) but failed to increase endothelial cyclic GMP levels or to
      elicit the relaxation of endothelium-intact porcine coronary arteries. In
      platelets, insulin also elicited the activation of Akt as well as the
      phosphorylation of eNOS and initiated NO production which was associated with
      increased cyclic GMP levels and the inhibition of thrombin-induced aggregation.
      The insulin-induced inhibition of aggregation was accompanied by a decreased
      Ca(2+) response to thrombin and was also prevented by N(omega) nitro-L-arginine.
      In platelets, but not in endothelial cells, insulin induced the activation of the
      AMP-activated protein kinase (AMPK), a metabolic stress-sensing kinase which was
      sensitive to the phosphatidylinositol 3-kinase (PI3-K) inhibitor wortmannin and
      the AMPK inhibitor iodotubercidin. Moreover, the insulin-mediated inhibition of
      thrombin-induced aggregation was prevented by iodotubercidin. Insulin-independent
      activation of the AMPK using 5-aminoimidazole-4-carboxamide ribonucleoside,
      increased platelet eNOS phosphorylation, increased cyclic GMP levels and
      attenuated platelet aggregation. These results highlight the differences in the
      signal transduction cascade activated by insulin in endothelial cells and
      platelets, and demonstrate that insulin stimulates the formation of NO in human
      platelets, in the absence of an increase in Ca(2+), by acti-vating PI3-K and AMPK
      which phosphorylates eNOS on Ser(1177).

PMID- 14597983
TI  - Mechanisms of the priming effect of low doses of lipopoly-saccharides on
      leukocyte-dependent platelet aggregation in whole blood.
AB  - Several studies focused on the ability of bacterial lipopolysac-charides (LPS) in
      triggering platelet and/or leukocyte activation. The aim of this study was to
      investigate the molecular mechanisms involved in the aggregation of platelets and
      in their interaction with leukocytes in whole blood after stimulation with low
      doses of LPS. LPS did not directly induce platelet aggregation in whole blood,
      but they primed the aggregation of platelets induced by epinephrine, adenosine
      diphosphate and arachidonic acid. As shown by cytofluorimetry, platelets neither
      bind FITC-LPS, nor express the LPS-receptors CD14 and toll-like receptor 4
      (TLR4). On the contrary, LPS primed monocytes and to a lesser extent
      polymorphonuclear neutrophils to adhere to platelets. Both platelet-leukocyte
      interaction and platelet aggregation in whole blood were inhibited by blockade of
      CD14 and TLR4. Moreover, the interaction between platelets and leukocytes was
      inhibited by P-selectin, and by blockade of PAF and reactive oxygen species,
      suggesting a role of P-selectin and of leukocyte-derived mediators. In
      conclusion, these results elucidate the mechanisms leading to platelet activation
      and interaction with leukocytes triggered by LPS. They suggest that the
      activation of platelets by LPS is mainly dependent on leukocytes and especially
      monocytes as a result of CD14 and TLR4 engagement. Moreover, we found that
      leukocyte-platelet interaction was triggered by the synthesis of PAF and the
      generation of oxygen radicals that induced upregulation of surface expression of
      P-selectin.

PMID- 14597984
TI  - Anti-oxidant ebselen delays microvascular thrombus formation in the rat cremaster
      muscle by inhibiting platelet P-selectin expression.
AB  - Ebselen, a seleno-organic compound showing glutathione per-oxidase-like activity,
      has potent anti-inflammatory and anti-oxidant effects. Since selenium deficiency
      is thought to be associated with an increased incidence of vascular thrombosis,
      we studied the effect of ebselen on blood cell aggregate formation and vessel
      occlusion in vivo. In individual microvessels of rat cremaster muscle
      preparations, photochemically induced thrombus formation was analyzed in detail
      using intravital fluorescence microscopy. In ebselen-pretreated animals (30 mg/kg
      ip), venular thrombus formation was significantly delayed (50% vessel occlusion:
      535+/-34 s; initial stasis: 872+/-82 s; complete occlusion: 908+/-87 s) as
      compared to vehicle-treated controls (416+/-42; 612+/-49; 647+/-51). Moreover,
      ebselen significantly prolonged the kinetics of arteriolar thrombus formation and
      even completely prevented blood cell aggregate and thrombus formation in 88.9% of
      all arterioles studied (p<0.05 vs controls: 37.5%). Anti-thrombotic properties of
      ebselen could also be observed in a model of ferric chloride-induced
      microvascular thrombosis, with a low dose (5 mg/kg ip) being as effective as a
      high dose pretreatment (30 mg/kg ip). As assessed by flow cytometry of platelet P
      selectin immunfluorescence, whole blood isolated from ebselen-treated animals
      revealed a significantly lower fraction of P-selectin expressing platelets when
      compared with that of DMSO-treated controls. In addition, oxidant stress-induced
      upregulation of P-selectin on isolated platelets was found dose-dependently
      inhibited by increasing concentrations of ebselen (10-100 micro M). Moreover,
      ebselen dose-dependently inhibited H(2)O(2)-induced platelet-leukocyte aggregate
      formation in whole blood in vitro, suggesting that the anti-thrombotic effect of
      ebselen is achieved by attenuation of P-selectin dependent platelet-leukocyte
      aggregation. Thus, ebselen represents preventive and therapeutic value for
      disorders with increased risk for oxidant stress-associated thrombotic events.

PMID- 14597985
TI  - Paris-Trousseau syndrome : clinical, hematological, molecular data of ten new
      cases.
AB  - Paris-Trousseau syndrome (PTS) is an inherited disorder characterized by mild
      hemorragic tendency associated with 11q chromosome deletion. Here we report ten
      new patients (5 boys, 5 girls) with complete clinical history, biological data,
      ultra-structural and molecular investigations. Thrombocytopenia is chronic in all
      the patients except two boys in whom it disappeared during the two first years of
      life. On Romanovsky stained peripheral blood smears, abnormal platelets with
      giant granules were detected in all the children and confirmed by electron
      microscopy (EM). On bone marrow smears, dysmegakaryopoiesis with many
      micromegakaryocytes was constantly observed. Abnormal alpha-granules were
      virtually absent from bone marrow and cultured megakaryocytes, while EM detected
      numerous images of granule fusion within blood platelets. Molecular analyses
      evidenced that the fli-1 gene is deleted in all the patients except one
      confirming the crucial role of the transcription factor FLI-1 in
      megakaryopoiesis. In summary, this study documents ten new cases of PTS with
      characteristic alpha-granule abnormalities, and shows the putative pathogenic
      role of fli-1 gene in the pathophysiology of this syndrome.

PMID- 14597986
TI  - Regulation of protease-activated receptor 1 (PAR1) on platelets and
      responsiveness to thrombin receptor activating peptide (TRAP) during systemic
      inflammation in humans.
AB  - Thrombin is a coagulation protease that activates platelets, endothelial cells,
      leukocytes and mesenchymal cells. Thrombin signaling is mediated at least in part
      by protease-activated receptors (PARs). As little is known about the in vivo
      regulation of PAR1, this study aimed to characterize the effects of systemic
      thrombin formation during human endotoxemia on the regulation of PAR1 and the
      associated responsiveness of human platelets to thrombin receptor activating
      peptide (TRAP). Endotoxin (2 ng/kg) was infused into 40 healthy men to study the
      regulation of PAR1 in systemic human inflammation. The SPAN12 antibody was used
      to determine the in vivo regulation of PAR1. To measure whether modulation of the
      PAR1 receptor may be associated with altered platelet reactivity, whole blood was
      stimulated with TRAP ex vivo. Thrombin generation was determined by prothrombin
      (F(1+2)) fragment. F(1+2) levels increased almost 9-fold from 0.5+/-0.1 nmol/L to
      4.5+/-1.9 nmol/L at 4 h (p<0.001). PAR1 decreased by approximately 8% (p<0.001)
      within 2 h after endotoxin infusion and stayed at those levels until 6 h.
      Concomitantly, TRAP induced P-selectin expression maximally decreased by 18%
      (p<0.001) at 6 h. In conclusion, PAR1 expression is down-regulated on platelets
      during systemic thrombin formation induced by inflammation in humans which
      results in decreased responsiveness to subsequent stimulation of the PAR1
      receptor.

PMID- 14597987
TI  - Antiinflammatory activity of astragaloside IV is mediated by inhibition of NF
      kappaB activation and adhesion molecule expression.
AB  - The regulated expression of adhesion molecules on the surface of endothelial
      cells is a key process in the pathogenesis of inflammation. The saponin
      astragaloside IV (AS-IV), a 3-O-beta-D-xylopyranosyl-6-O-beta-D
      glucopyranosylcycloastragenol purified from the Chinese medical herb Astragalus
      membranaceus (Fisch) Bge. has been shown to have anti-inflammatory effects in
      vivo. In this study we have investigated the effect of AS-IV on cytokine-and LPS
      stimulated expression of adhesion molecules in and leukocyte adhesion to
      endothelial cells. We have demonstrated that AS-IV significantly reduced the
      adhesion promoting activity of LPS-stimulated HUVECs for polymorph-nuclear
      leukocytes (PMNs) and the monocytic cell line THP-1. Furthermore, by using
      specific cell ELISAs we could show that AS-IV decreased the LPS-induced
      expression of E-selectin and VCAM-1 on the surface of HUVECs in a dose and time
      dependent manner, whereas the expression of ICAM-1 was not affected by AS-IV. AS
      IV also inhibits TNFalpha-induced VCAM-1 expression. The saponin octyl-D
      glucopyranoside had no effect on the LPS-induced expression of E-selectin and
      VCAM-1 excluding an unspecific detergent-like effect of AS-IV. Moreover, AS-IV
      significantly inhibited LPS- and TNFalpha-induced specific mRNA levels for E
      selectin and VCAM-1. Finally, we could show that AS-IV completely abolished LPS-
      and TNFalpha-induced nuclear translocation of NF-kappaB and NF-kappaB DNA binding
      activity in endothelial cells. We conclude that the ability of AS-IV to inhibit
      the NF-kappaB pathway might be one under-lying mechanism contributing to its anti
      inflammatory potential in vivo.

PMID- 14597988
TI  - Soluble CD146, a novel endothelial marker, is increased in physiopathological
      settings linked to endothelial junctional alteration.
AB  - CD146, a novel cell adhesion molecule localized at the endothelial junction, is
      involved in the control of cell-cell cohesion. It is found as a soluble form in
      conditioned medium of cultured endothelial cells. We developed an ELISA and
      report for the first time the presence of a soluble form of CD146 (sCD146) in the
      plasma of healthy subjects. Mean sCD146 values (260 +/- 60 ng/ml) were higher in
      subjects over 50 years and in men. We therefore investigated sCD146 values in
      patients with chronic renal failure (CRF), a clinical setting associated with
      junctional alterations. A significant increase in sCD146 was found in patients
      with CRF matched with controls (457 +/- 181 ng/ml versus 288 +/- 82 ng/ml
      respectively, p<0.0001). This increase was corroborated by increased endothelial
      expression of CD146 on kidney biopsies from patients with CRF. In contrast, in
      patients with CRF no modulation was observed for the soluble and cell-associated
      form of CD31, another junctional molecule. Together these data indicate that
      sCD146 circulates in the plasma of healthy subjects. Modifications of its basal
      levels could reflect alterations of junctional functions such as vascular
      permeability.

PMID- 14597989
TI  - Aminopeptidase inhibitor bestatin stimulates microvascular endothelial cell
      invasion in a fibrin matrix.
AB  - The aminopeptidase inhibitor bestatin has been shown to have anti-angiogenic
      effects in a number of model systems. These effects are thought to result from
      inhibition of CD13 activity. Because tumor angiogenesis can evolve in a fibrin
      rich stroma matrix we have studied for the first time the effects of bestatin on
      microvascular endothelial capillary-like tube formation in a fibrin matrix.
      Bestatin enhanced the formation of capillary-like tubes dose-dependently. Its
      effects were apparent at 8 micro M; the increase was 3.7-fold at 125 micro M;
      while high concentrations (>250 micro M), that were shown to have anti-angiogenic
      effects in other systems, caused extensive matrix degradation. Specific CD13
      blocking antibodies WM15 and MY-7, and the aminopeptidase inhibitors amastatin
      and actinonin also enhanced capillary-like tube formation (maximally 1.5-fold),
      but these effects did not reach statistical significance. The effect of bestatin
      was not due to a change in uPAR availability because the relative involvement of
      the u-PA/u-PAR activity was not altered by bestatin. In view of the present
      findings we hypothesize that aminopeptidases other than CD13 predominantly
      contribute to the observed pro-angiogenic effect of bestatin in a fibrin matrix.
      The identification of this novel effect of bestatin is important in the light of
      the proposed use of bestatin as anti-angiogenic and/or anti-tumor agent.

PMID- 14597990
TI  - PML/RARalpha plays a role for basal activity and retinoid-induced repression of
      the tissue factor promoter in acute promyelocytic leukemia cells.
AB  - Constitutive expression of tissue factor (TF) by acute promyelocytic leukemia
      (APL) cells may contribute to thrombotic complications. In this study we examined
      the transcriptional mechanisms of all-trans retinoic acid (ATRA)-induced down
      regulation of TF in the APL cell line NB4, by analysis of stable clones
      expressing the luciferase gene under the control of 5' flanking regions of the TF
      gene. We show that the TF promoter is constitutively active in NB4 cells, and
      that ATRA induces rapid suppression of the promoter. Basal activity and ATRA
      induced suppression of TF promoter is determined by the proximal -383 to +121 bp
      of the promoter. Electrophoretic mobility shift assays demonstrate the binding of
      Fos/Jun complexes to two TF promoter AP-1 sites in this region. Both complexes
      were suppressed by ATRA treatment. The ectopic expression of the APL-specific
      PML/RARalpha oncoprotein in U-937 cells results in induction of TF mRNA and
      promoter activity. Interestingly, this PML/RARalpha-mediated increase in TF
      promoter activity is sensitive to ATRA treatment. These data indicate that TF
      expression in APL cells is exacerbated by the presence of the PML/RARalpha fusion
      protein, and implicates the loss of Fos/Jun binding to the TF promoter in ATRA
      induced suppression of TF.

PMID- 14597991
TI  - Assessment of platelet activation in several different anticoagulants by the
      Advia 120 Hematology System, fluorescence flow cytometry, and electron
      microscopy.
AB  - In vivo platelet activation results are often confounded by activation induced in
      vitro during the preparative procedures. We measured ex vivo (basal) and in vitro
      (thrombin-induced) platelet activation in sodium citrate,
      ethylenediaminetetraacetic acid (EDTA), and Citrate Theophylline Dipyridamole
      Adenosine (CTAD) whole blood specimens. Determinations were made by measurements
      of platelet density (mean platelet component: MPC concentration) on the Advia 120
      Hematology System. The MPC has been previously shown to correlate with a
      fluorescence flow cytometric method, also determined in this study, using the
      surface expression of CD62P. Moreover, platelet shape and structure changes in
      EDTA and CTAD anticoagulated whole blood specimens were characterized by
      transmission electron microscopy (TEM). Observations made using the Advia 120
      Hematology System platelet density parameter, MPC, in the absence of thrombin
      were 25.7 +/- 0.9 g/dl, 27.9 +/- 0.9 g/dl and 24.8 +/- 1.2 g/dl in sodium
      citrate, EDTA and CTAD whole blood specimens, respectively. Addition of thrombin
      induced a significant change in platelet MPC for sodium citrate (21.9 +/- 1.9
      g/dl; p<0.0001) and EDTA (23.2 +/- 0.9 g/dl; p<0.0001) whole blood specimens. In
      contrast, thrombin had no effect on MPC measured in whole blood taken into CTAD
      tubes. In vitro fluorescence flow cytometric platelet activation experiments
      measuring the percentage of platelets expressing anti-CD62P showed increase in
      sodium citrate specimens from 9.2 +/- 7.0 to 55.5 +/- 23.1 % (p<0.0001) and in
      EDTA specimens from 1.9 +/- 1.7 to 64.6 +/- 12.4 % (p<0.0001) after addition of
      thrombin. However, in blood taken into CTAD tubes, there was no significant
      change. Studies on platelets isolated from whole blood in CTAD showed activation
      by thrombin indicating that platelets in CTAD, while protected in its presence
      remained functional upon its removal. When observed by TEM over time, platelets
      in EDTA appear more activated and contain fewer granules than platelets in CTAD.
      We conclude that CTAD demonstrates in vitro platelet activation inhibition and
      may be useful in stabilizing ex vivo platelet activation. The novel platelet
      activation parameter, MPC, measured by an automated routine hematology system,
      using customized proprietary software, may be used in conjunction with CTAD, a
      stabilizing anticoagulant, to measure the ex vivo platelet activation state in
      whole blood specimens. TEM studies verify shape modifications and simultaneous
      retention of intracellular granules at early post-venipuncture time periods in
      CTAD specimens.

PMID- 14597992
TI  - Ultrasound screening for distal vein thrombosis is not beneficial after major
      orthopedic surgery. A randomized controlled trial.
AB  - Ultrasound screening for deep vein thrombosis (DVT) after orthopedic surgery
      revealed thrombosis in up to 30% of patients, but the clinical impact of
      screening for distal thrombosis has not been established. Three hundred and forty
      six patients after hip or knee replacement and postoperative standard prophylaxis
      of 10 days low molecular weight heparin (LMWH) were randomized to receive either
      prolonged prophylaxis with LMWH or postoperative ultrasound screening for
      proximal and distal thrombosis. All thrombosis found in screening was treated.
      Patients with a negative screening test did not receive any heparin after day 10.
      The cumulative rate of proximal thrombosis and symptomatic pulmonary embolism
      until day 35 postoperatively was determined. In 174 screening patients,
      ultrasound found 55 cases of distal (31.6%) and 9 cases of proximal (5.1%) in
      hospital thrombosis. In 108 screening patients without thrombosis at discharge 7
      new distal (6.5%) and 6 new proximal (5.6%) thrombotic events occurred by day 35.
      In 163 patients with prolonged prophylaxis, 33 cases of distal (20.2%) and 7
      cases of proximal (4,3%) thrombotic events occurred by day 35. The cumulative
      rate of proximal events was 8,7% in the screening group and 4.3% in the
      prophylaxis group (p=0.12). In conclusion, ultrasound screening for thrombosis
      does not reduce the rate of proximal thrombosis and symptomatic pulmonary
      embolism 35 days after hip or knee replacement surgery.

PMID- 14597993
TI  - ADAMTS 13 genotype and vWF protease activity in an Italian family with TTP.

PMID- 14597994
TI  - Stroke due to left carotid thrombosis in moderate ovarian hyperstimulation
      syndrome.

PMID- 14597995
TI  - Genome-wide linkage analysis of von Willebrand factor plasma levels implicates
      the ABO locus as a principal determinant: should we overlook ADAMTS13?

PMID- 14597997
TI  - Deep vein thrombosis after orthopedic surgery in a patient with type 1 von
      Willebrand disease and mutations in the MTHFR and beta-fibrinogen genes.

PMID- 14597998
TI  - Recurrent thromboembolism in fertile women with venous thrombosis: incidence and
      risk factors.

PMID- 14597999
TI  - Role of nonclassical class I genes of the chicken major histocompatibility
      complex Rfp-Y locus in transplantation immunity.
AB  - The chicken major histocompatibility complex ( MHC) genes are organized into two
      genetically independent clusters which both possess class I and class IIbeta
      genes: the classical B complex and the Restriction fragment pattern- Y ( Rfp-Y)
      complex. In this study, we have examined the role of Rfp-Y genes in
      transplantation immunity. For this we used three sublines, B19H1, B19H2 and
      B19H3, derived from a line fixed for B19. Southern blots, PCR-SSCP assays using
      primers specific for Rfp-Y genes, and Rfp-Y class I allele-specific sequencing
      show that the polymorphisms observed in B19H1, B19H2 and B19H3 are due to the
      presence of three different Rfp-Y haplotypes. The Rfp-Y class I ( YF) alleles in
      these three haplotypes are highly polymorphic, and RT-PCR shows that at least two
      YF loci are expressed in each subline. The three sublines show Rfp-Y-directed
      alloreactivity in that Rfp-Y-incompatible skin grafts are rejected within 15
      days, a rate intermediate between that seen in B-incompatible rejection (7 days)
      and that observed for grafts within the sublines (20 days). We conclude that Rfp
      Y has an intermediate role in allograft rejection, likely to be attributable to
      polymorphism at the class I loci within this region.

PMID- 14598000
TI  - The influence of cell volume changes on tumour cell proliferation.
AB  - Ion channels and cell volume control participate in a wide variety of cellular
      functions, including cell proliferation. According to the "pump-leak model" or
      the "double Donnan system", the cell volume is constant in physiological medium
      so long as the cell metabolism and the Na-K pump are not inhibited and the
      passive Na+ permeability is not dramatically increased. At short term, this model
      has been supported by a large number of experiments made on different cell types.
      However, at long term, it may be insufficient to describe the volume control
      because it does not take into account the fact that cells possess a large number
      of membrane transporters and interconnected volume regulatory mechanisms. In this
      review, we present recent results indicating that, in physiological conditions,
      ion channels may have important roles in cell volume control. Furthermore, we
      emphasize that cell proliferation and volume are phenomenologically correlated.
      On the basis of the macromolecular crowding theory, the possibility that the cell
      osmolyte and water content mediates this correlation is discussed.

PMID- 14598001
TI  - Ion permeation of pores in model membranes: selectivity, fluctuations and the
      role of surface charge.
AB  - Fluctuation of surface charge on pore walls provides a realistic, additional
      mechanism for generating fluctuation of ionic current and ionic selectivity in
      narrow pores.

PMID- 14598002
TI  - Effect of imipramine on linear and nonlinear measures of heart rate variability
      in children.
AB  - We investigated the effects of treatment with the tricyclic antidepressant (TCA)
      imipramine in eight children in supine and standing postures. We used 256 seconds
      of real-time data for the analyses. Spectral analysis showed a significant
      decrease of high-frequency (HF) power (0.15-0.5 Hz), especially in the standing
      posture. Low frequency (LF) HF ratios were significantly higher in the standing
      posture after treatment, suggesting increased sympathovagal interaction. We also
      obtained the nonlinear measures of fractal dimension (FD), and approximate
      entropy (APEN). Although the FD of heart rate was significantly lower in the
      standing posture, APEN was significantly decreased after treatment in either
      posture and was the most sensitive measure in this study. These findings suggest
      a decreased cardiac vagal function with a relative increase in sympathetic
      responsiveness, which may in part be related to the cardiotoxicity of these
      drugs. These findings are discussed in relation to the cardiovascular side
      effects of TCAs.

PMID- 14598003
TI  - Kinematics of wrist joint flexion in overarm throws made by skilled subjects.
AB  - Previous studies of multijoint arm movements have shown that the CNS holds arm
      kinematics constant in different situations by predictively compensating for the
      effects of interaction torques. We determined whether this was also the case for
      wrist joint flexion in natural overarm throws performed by skilled subjects in
      3D, a situation where large passive torques can occur at the wrist. Specifically,
      we investigated whether wrist flexion amplitudes are held constant in throws of
      different speeds. Joint rotations were recorded at 1,000 Hz with the search-coil
      technique. Contrary to a previous study on constrained 2D throwing, indirect
      evidence was found that in fast throws passive torques associated with forearm
      deceleration were exploited to increase wrist flexion velocity. This increase in
      wrist flexion velocity was associated with constant wrist flexion amplitudes at
      ball release (mean 27 degrees) for throws of different speeds. Furthermore, final
      wrist flexion positions after ball release were similar for a particular subject
      irrespective of the speed of the throw. This was associated in faster throws with
      increased magnitudes of wrist flexor and wrist extensor EMG activity which damped
      passive torques associated with forearm angular deceleration. It is concluded
      that wrist flexion in overarm throws of different speeds is produced by central
      signals which precisely control net joint torque by both exploiting and damping
      passive torques during different parts of the throw to keep wrist joint angular
      position parameters constant. As such the results show that control strategies
      for natural 3D throwing are different from those for constrained 2D throwing.

PMID- 14598004
TI  - Derivatization of neutral steroids to enhance their detection characteristics in
      liquid chromatography-mass spectrometry.
AB  - This review article underlines the detection-oriented derivatization of neutral
      steroids in liquid chromatography-mass spectrometry (LC-MS). Steroids have strong
      biological activity at very low concentrations in target tissues and, therefore,
      the analysis of steroids in body fluids or tissues is necessary to elucidate the
      nature of the many endocrine disease processes and thus be useful for diagnosis
      and treatment. LC-MS has recently been used for steroid analysis because of its
      specificity and versatility, but the ionization efficiencies of most steroids are
      relatively low for the different ionization methods. Derivatization enhances the
      ionization efficiencies of steroids, leading to high sensitivity and specific
      detection. For electrospray ionization MS the introduction of permanently charged
      moieties or easily ionizable moieties effectively increases the sensitivity of
      detection of steroids. The introduction of moieties with proton affinity or
      electron affinity enhances the analyte signals in positive and negative
      atmospheric pressure chemical ionization MS, respectively.

PMID- 14598006
TI  - Determination of cannabinoids in hemp food products by use of headspace solid
      phase microextraction and gas chromatography-mass spectrometry.
AB  - A fully automated procedure using alkaline hydrolysis and headspace solid-phase
      microextraction (HS-SPME), followed by on-fiber derivatization and gas
      chromatographic-mass spectrometric (GC-MS) detection has been developed for
      determination of cannabinoids in hemp food samples. After addition of a
      deuterated internal standard, the sample was hydrolyzed with sodium hydroxide and
      submitted to direct HS-SPME. After absorption of analytes for on-fiber
      derivatization, the fiber was placed directly into the headspace of a second vial
      containing N-methyl- N-trimethylsilyltrifluoroacetamide (MSTFA), before GC-MS
      analysis. Linearity was good for Delta(9)-tetrahydrocannabinol (THC),
      cannabidiol, and cannabinol; regression coefficients were greater than 0.99.
      Depending on the characteristics of the matrix the detection limits obtained
      ranged between 0.01 and 0.17 mg kg(-1) and the precision between 0.4 and 11.8%.
      In comparison with conventional liquid-liquid extraction this automated HS-SPME
      GC-MS procedure is substantially faster. It is easy to perform, solvent-free, and
      sample quantities are minimal, yet it maintains the same sensitivity and
      reproducibility. The applicability was demonstrated by analysis of 30 hemp food
      samples. Cannabinoids were detected in all of the samples and it was possible to
      differentiate between drug-type and fiber-type Cannabis sativa L. In comparison
      with other studies relatively low THC concentrations between 0.01 and 15.53 mg
      kg(-1) were determined.

PMID- 14598007
TI  - COMAR2--the internet database for certified reference materials.

PMID- 14598008
TI  - Iron analysis in atmospheric water samples by atomic absorption spectroscopy
      (AAS) in water-methanol.
AB  - To distinguish between Fe(II) and Fe(III) species in atmospheric water samples,
      we have adapted an analytical procedure based on the formation of a specific
      complex between Fe(II) and ferrozine (FZ) on a chromatographic column. After
      elution of Fe(III), the Fe(II) complex is recovered with water-methanol (4:1).
      The possibility of trace iron measurements in this complex medium by graphite
      furnace atomic-absorption spectrometry has been investigated. A simplex
      optimization routine was required to complete the development of the analytical
      method.

PMID- 14598009
TI  - Chemical modifiers in arsenic determination in biological materials by tungsten
      coil electrothermal atomic absorption spectrometry.
AB  - Palladium, iridium, and rhodium are evaluated as possible chemical modifiers in
      the determination of As in digest solutions of biological materials (human hair
      and clam) by tungsten coil electrothermal atomic absorption spectrophotometry
      (TCA-AAS). The modifier in solution was applied onto the coil and thermally pre
      reduced; the pre-reduction conditions, the amount of modifier, and the thermal
      program were optimized. Palladium was not satisfactory, whereas Ir and Rh were
      effective modifiers and rendered better relative sensitivity for As by a factor
      of 1.4 and 1.9, respectively compared to the case without modifier. Upon
      optimization of thermal conditions for As in pre-reduced Ir (2.0 microg) and Rh
      (2.0 microg) modifiers and in the digest solutions of the study matrices, Rh (2.0
      microg) was more effective modifier and was selected as such. The mean within-day
      repeatability was 2.8% in consecutive measurements (25-100 microg L(-1)) (3
      cycles, each of n=6) and confirmed good short-term stability of the absorbance
      measurements. The mean reproducibility was 4.4% (n=20 in a 3-day period) and the
      detection limit (3 sigmablank/slope) was 29 pg (n=15). The useful coil lifetime
      in Rh modifier was extended to 300-400 firings. Validation was by determination
      of As in the certified reference material (CRM) of "Oyster tissue" solution with
      a percentage relative error (Erel%) of 2% and percentage relative standard
      deviation (RSD%) of 3% (n=4), and by analytical recovery of As spiked in CRM of
      human hair [94 +/- 8% (n=4)]. The methodology is simple, fast (sample readout
      frequency 21 h(-1)), reliable, of low cost, and was applied to the determination
      of As in hair samples of exposed and unexposed workers.

PMID- 14598010
TI  - Analytical control of photocatalytic treatments: degradation of a sulfonated azo
      dye.
AB  - The degradation of Methyl Orange (C(14)H(14)N(3)SO(3)Na), chosen as a model
      sulfonated azo dye, was investigated in aqueous solutions containing suspended
      polycrystalline TiO(2) particles under irradiation with simulated sunlight. The
      dye disappearance and the formation of the mineralization end products were
      monitored; the formation of the main transient intermediates was also examined in
      detail. Particular attention was devoted to the identification and to the
      evolution of fragments retaining the chromophoric group. The comparison of data
      coming from various analytical techniques led to a possible reaction mechanism
      for the degradation process, giving insight into an aspect of the treatment which
      has not been considered in previous studies.

PMID- 14598011
TI  - Recent trends in mass spectrometer development.
AB  - Trends in mass analyzer development are reviewed here with an emphasis on tandem
      mass spectrometers. The move toward "hybridization" of conventional mass
      analyzers to allow additional instrument functionality in tandem mass
      spectrometry is discussed.

PMID- 14598012
TI  - Development of a simplified method for the simultaneous determination of retinol,
      alpha-tocopherol, and beta-carotene in serum by liquid chromatography-tandem mass
      spectrometry with atmospheric pressure chemical ionization.
AB  - A new and simple method for the determination of fat-soluble vitamins (retinol,
      alpha-tocopherol, and beta-carotene) in human serum was developed and validated
      by using liquid chromatography-tandem mass spectrometry with atmospheric pressure
      chemical ionization (LC-APCI-MS-MS). Different solvent mixtures were tested to
      obtain deproteinization and extraction of the analytes from the matrix. As a
      result, a volume of 240 microL of a 1:1 (v/v) ethanol/ethyl acetate mixture added
      to 60 microL of serum was found to be suitable for both protein precipitation and
      antioxidants solubilization, giving the best recovery for all three analytes.
      Deproteinized samples (20 microL) were injected after dilution, without the need
      for concentration or evaporation to dryness and reconstruction of the sample.
      Vitamins were separated on a C-8 column using a 95:5 (v/v)
      methanol/dichloromethane mixture and ionized in the positive-ion mode; detection
      was performed in the selected-reaction monitoring mode. Linearity of the LC-APCI
      MS-MS method was established over 5 orders of magnitude for retinol and alpha
      tocopherol, whereas in the case of beta-carotene it was limited to 4 orders.
      Lower limits of quantitation were 1.7, 2.3, and 4.1 nM for retinol, alpha
      tocopherol, and beta-carotene, respectively. Serum concentrations of retinol,
      alpha-tocopherol, and alpha+beta-carotene determined in a group of healthy
      volunteers were 2.48, 38.07, and 0.50 microM, respectively, in samples collected
      in winter ( n=122) and 2.69, 45.88, and 0.90 microM during summer ( n=66).

PMID- 14598013
TI  - A rapid HPLC method for the determination of carboxylic acids in human urine
      using a monolithic column.
AB  - A rapid HPLC method for the determination of carboxylic acids in urine samples
      using a Chromolith Performance RP/18e 100/4.6 with Chromolith Guard Cartridge
      RP/18e 10/4.6 (Merck KgaA, Darmstadt, Germany) was developed. The method
      facilitates the simultaneous determination of aromatic hydrocarbon metabolites
      mandelic acid (MA) and phenylglyoxylic acid (PGA) from styrene and ethylbenzene,
      hippuric acid (HA) from toluene and 2-, 3-, 4-methylhippuric acids (MHA) from
      xylene. 3-hydroxybenzoic acid (3-HBA) was used as internal standard. A
      chromatographic run is completed within less than 5 min for styrene, ethylbenzene
      and toluene metabolites, and within 10 min for xylene metabolites. The detection
      limits are 9 mg L(-1) urine for MA, 1.25 mg L(-1) urine for PGA, 4.9 mg L(-1)
      urine for HA, 22 mg L(-1) urine for 2-MHA, and 18.5 mg L(-1) urine for 3-MHA. No
      significant differences of the MA, PGA and HA concentrations in human urine
      samples obtained by HPLC chromatography on LiChrosorb RP 18 and on Chromolith
      RP/18e columns were found. The results were evaluated by using ANOVA.

PMID- 14598014
TI  - Epidemiological estimates of risk in the process of becoming dependent upon
      cocaine: cocaine hydrochloride powder versus crack cocaine.
AB  - RATIONALE: To estimate the risk of experiencing clinical features of cocaine
      dependence within 1-2 years of starting cocaine use, and to examine whether crack
      smoking might increase this risk. METHODS: A national sample of recent-onset
      cocaine users was identified within public data files of the National Household
      Surveys on Drug Abuse (NHSDA) for the years 1995 through 1998. The sample
      included 572 recent-onset users of cocaine HCl powder but not crack, and 190
      recent-onset users of crack, some of whom had also started use of cocaine powder
      no more than 23 months prior to assessment. A separate group of 93 recent-onset
      crack users was identified; this comparison group had started using cocaine HCl
      powder 2+ years before assessment. Cocaine dependence was assessed via seven
      standardized questions about clinical features experienced within 12 months of
      assessment, such as feeling unable to cut down. Multivariate response regressions
      were used to evaluate crack-associated excess risk and clinical profiles of
      cocaine dependence. RESULTS: Among persons who had recently started to use
      cocaine HCl powder but not crack cocaine, about 5-12% experienced clinical
      features of cocaine dependence. Most clinical features occurred 2-3 times more
      often among crack smoking users as compared to those using powder only, even with
      statistical adjustment for frequency of cocaine use ( P<0.01). This crack
      associated excess risk is more prominent for several clinical features of cocaine
      dependence, including tolerance associated with cocaine use and narrowed
      behavioral repertoire attributed to cocaine use. CONCLUSIONS: This new
      epidemiological evidence suggests that crack-smoking may increase risk of cocaine
      dependence once cocaine use starts, but we cannot rule out the possibility that
      crack users start out with a greater susceptibility to become cocaine dependent.

PMID- 14598015
TI  - Imagination and attention: protecting participants in psychopharmacological
      research.

PMID- 14598017
TI  - Increases in food intake or food-seeking behavior induced by GABAergic, opioid,
      or dopaminergic stimulation of the nucleus accumbens: is it hunger?
AB  - RATIONALE: Previous work has shown that stimulation of GABAergic, opioid, or
      dopaminergic systems within the nucleus accumbens modulates food intake and food
      seeking behavior. However, it is not known whether such stimulation mimics a
      motivational state of food deprivation that commonly enables animals to learn a
      new operant response to obtain food. OBJECTIVES: In order to address this
      question, acquisition of lever pressing for food in hungry animals was compared
      with acquisition in non-food-deprived rats subjected to various nucleus accumbens
      drug treatments. METHODS: All animals were given the opportunity to learn an
      instrumental response (a lever press) to obtain a food pellet. Prior to training,
      ad lib-fed rats were infused with the gamma-aminobutyric acid (GABA)A agonist
      muscimol (100 ng/0.5 microl per side) or the mu-opioid receptor agonist D-Ala2, N
      me-Phe4, Gly-ol5-enkephalin (DAMGO, 0.25 microg/0.5 microl per side), or saline
      into the nucleus accumbens shell (AcbSh). The indirect dopamine agonist
      amphetamine (10 microg/0.5 microl per side) was infused into the AcbSh or nucleus
      accumbens core (AcbC) of ad lib-fed rats. An additional group was food deprived
      and infused with saline in the AcbSh. Chow and sugar pellet intake responses
      after drug treatments were also evaluated in free-feeding tests. RESULTS:
      Muscimol, DAMGO, or amphetamine did not facilitate acquisition of lever pressing
      for food, despite clearly increasing food intake in free-feeding tests. In
      contrast, food-deprived animals rapidly learned the task. CONCLUSIONS: These
      findings suggest that pharmacological stimulation of any of these neurochemical
      systems in isolation is insufficient to enable acquisition of a food-reinforced
      operant task. Thus, these selective processes, while likely involved in control
      of food intake and food-seeking behavior, appear unable to recapitulate the
      conditions necessary to mimic the state of negative energy balance.

PMID- 14598016
TI  - Serotonergic/glutamatergic interactions: the effects of mGlu2/3 receptor ligands
      in rats trained with LSD and PCP as discriminative stimuli.
AB  - RATIONALE: On the basis of electrophysiological evidence, it has been proposed
      that both antagonism of NMDA receptors by drugs such as PCP and stimulation of 5-
      HT(2A) receptors by drugs such as LSD result in the release of glutamate.
      Furthermore, it has been observed that antagonists and agonists at mGlu(2/3)
      receptors increase and decrease, respectively, the release of glutamate. Taken
      together, these observations predict behaviorally significant interactions
      between ligands at mGlu(2/3) receptors and hallucinogens such as LSD and PCP.
      OBJECTIVE: The present study sought to test in rats the glutamate hypothesis of
      hallucinogenesis using drug-induced stimulus control as the dependent variable
      and selected glutamatergic and serotonergic receptor ligands as independent
      variables. METHODS: Male F-344 rats were trained in a two-lever, fixed ratio 10,
      food-reinforced task with either phencyclidine (PCP; 3.0 mg/kg; i.p.; 30 min
      pretreatment) or lysergic acid diethylamide (LSD; 0.1 mg/kg; IP; 15 min
      pretreatment) as discriminative stimuli. The interactions of PCP and the
      mGlu(2/3) selective ligands, LY341495 and LY379268, with stimulus control by LSD
      were determined. The effects of these drugs were compared with those of
      serotonergic antagonists known to antagonize the stimulus effects of LSD,
      specifically, pirenperone and M100907. RESULTS: Stimulus control by LSD was
      potentiated by both PCP and the mGlu(2/3) antagonist, LY341495. In tests of
      antagonism, stimulus control by LSD was significantly but incompletely diminished
      by the mGlu(2/3) agonist, LY379268; this result was in contrast with the complete
      antagonism of LSD by both pirenperone and M100907. In PCP-trained rats, LY341495
      was without effect on stimulus control by an intermediate dose of PCP. In
      contrast, the training dose of PCP was significantly but incompletely antagonized
      by LY379268. CONCLUSIONS: These data, obtained using a stimulus control model of
      the hallucinogenic effects of PCP and LSD, provide support for the hypothesis
      that glutamate release is a factor in hallucinogenesis by both 5-HT(2) agonists
      and non-competitive NMDA antagonists.

PMID- 14598018
TI  - Low platelet MAO activity associated with high dysfunctional impulsivity and
      antisocial behavior: evidence from drunk drivers.
AB  - RATIONALE: Low platelet monoamine oxidase (MAO) activity is associated with
      problem drinking and other deviant behaviors. Since the majority of alcohol
      abusers are smokers, and tobacco smoke has a direct inhibitory effect on the
      enzyme, these associations may not be meaningful. OBJECTIVE: The authors compared
      platelet MAO activity and impulsivity in police-referred subjects caught driving
      while intoxicated and in control subjects, controlling for smoking. METHODS:
      Platelet MAO activity was measured radioenzymatically and impulsivity scores
      obtained from questionnaires. Smoking status was self-reported. RESULTS: Subjects
      caught driving while intoxicated had significantly higher dysfunctional
      impulsivity and lower platelet MAO activity than control subjects. This
      difference in platelet MAO activity between the two groups was significant in non
      smokers and ex-smokers. CONCLUSIONS: These findings demonstrate that platelet MAO
      activity is lower in subjects with socially deviant behavior, and the association
      of low platelet MAO and problem drinking is not an artifact of smoking.

PMID- 14598019
TI  - Impact of genetic polymorphisms in transmembrane carrier-systems on drug and
      xenobiotic distribution.
AB  - Active transport across biological membranes has become a noticeable factor in
      the absorption, distribution, and excretion of an increasing number of drugs.
      Different transmembrane transport systems including organic anion transporters
      (OATP, solute carrier family SLC21A), organic cation transporters (OCT, SLC22A),
      dipeptide transporters (PEPT, SLC15A), nucleoside transporters (CNT, SLC28A),
      monocarboxylate carriers (MCT, SLC2A), and members of the large ATP-binding
      cassette family (ABC, SLC3A) are involved in drug disposition. Genetic
      polymorphisms in transport proteins frequently occur and contribute to
      interindividual differences in the efficacy and safety of pharmatherapy.
      Currently, the most advanced research has been done on P-glycoprotein (ABCB1,
      SLC3A1.201.1). Knowledge of this transporter indicates that haplotype analysis
      rather than association with single nucleotide polymorphisms (SNPs) provides the
      most appropriate interpretation of pharmacogenetic data from drug transporters.
      This review gives an overview and update on the pharmacological impact of genetic
      variants in transmembrane transporters.

PMID- 14598020
TI  - Pharmacological profile of the cyclic nociceptin/orphanin FQ analogues
      c[Cys10,14]N/OFQ(1-14)NH2 and c[Nphe1,Cys10,14]N/OFQ(1-14)NH2.
AB  - In this study we describe the activity of two cyclic nociceptin/orphanin FQ
      (N/OFQ) peptides; c[Cys(10,14)]N/OFQ(1-14)NH(2) (c[Cys(10,14)]) and its [Nphe(1)]
      derivative c[Nphe(1),Cys(10,14)]N/OFQ(1-14)NH(2) (c[Nphe(1),Cys(10,14)]) in
      native rat and mouse and recombinant human N/OFQ receptors (NOP). Cyclisation may
      protect the peptide from metabolic degradation. In competition binding studies of
      rat, mouse and human NOP the following rank order pK(i) was obtained: N/OFQ(1
      13)NH(2)(reference agonist)>N/OFQ=c[Cys(10,14)]>>c[Nphe(1)Cys(10,14)]. In
      GTPgamma(35)S studies of Chinese hamster ovary cells expressing human NOP
      (CHO(hNOP)) c[Cys(10,14)] (pEC(50) 8.29) and N/OFQ(1-13)NH(2) (pEC(50) 8.57) were
      full agonists whilst c[Nphe(1)Cys(10,14)] alone was inactive. Following 30 min
      pre-incubation c[Nphe(1)Cys(10,14)] competitively antagonised the effects of
      N/OFQ(1-13)NH(2) with a pA(2) and slope factor of 6.92 and 1.01 respectively. In
      cAMP assays c[Cys(10,14)] (pEC(50) 9.29, E(max) 102% inhibition of the forskolin
      stimulated response), N/OFQ(1-13)NH(2) (pEC(50) 10.16, E(max) 103% inhibition)
      and c[Nphe(1)Cys(10,14)] (~80% inhibition at 10 microM) displayed agonist
      activity. In the mouse vas deferens c[Cys(10,14)] (pEC(50) 6.82, E(max) 89%
      inhibition of electrically evoked contractions) and N/OFQ(1-13)NH(2) (pEC(50)
      7.47, E(max) 93% inhibition) were full agonists whilst c[Nphe(1)Cys(10,14)] alone
      was inactive. c[Nphe(1)Cys(10,14)] (10 microM) competitively antagonised the
      effects of N/OFQ(1-13)NH(2) with a pK(B) of 5.66. In a crude attempt to assess
      metabolic stability, c[Cys(10,14)] was incubated with rat brain membranes and
      then the supernatant assayed for remaining peptide. Following 60 min incubation
      64% of the 1 nM added peptide was metabolised (compared with 54% for N/OFQ
      NH(2)). In summary, we report that c[Cys(10,14)] is a full agonist with a small
      reduction in potency but no improvement in stability whilst c[Nphe(1)Cys(10,14)]
      displays tissue (antagonist in the vas deferens) and assay (antagonist in the
      GTPgamma(35)S assay and agonist in cAMP assay) dependent activity.

PMID- 14598021
TI  - The hepatocellular bile acid transporter Ntcp facilitates uptake of the lethal
      mushroom toxin alpha-amanitin.
AB  - Hepatotoxicity caused by the mushroom poison alpha-amanitin is an unusual but
      serious cause of death and liver transplantation. Understanding the mechanisms of
      alpha-amanitin uptake may lead to rational therapeutic approaches. Because older
      data suggested that a sodium-dependent bile acid transporter is responsible for
      alpha-amanitin uptake, we tested the hypothesis that Na(+)-taurocholate
      cotransporter polypeptide (Ntcp) facilitates hepatocellular alpha-amanitin
      uptake. Human hepatoblastoma cells (HepG2), cells that have lost native Ntcp
      expression, were stably transfected with the rat Ntcp gene. Taurocholate uptake
      by the transfected cells exhibited a physiologically normal K(m) and V(max). A
      toxicologically relevant functional assay for alpha-amanitin uptake was developed
      by measuring its ability to block cytokine-induced synthesis of interleukin-1
      receptor antagonist (IL-1Ra) mRNA. Treatment with interleukin-1beta (10 ng/ml)
      and interleukin-6 (100 ng/ml) increased IL-1Ra mRNA abundance 8.6-fold and 15.6
      fold in HepG2 cells and Ntcp-transfected cells, respectively. Pretreatment of
      transfected cells with 1 micro M alpha-amanitin for 6-10 h almost completely
      blocked induction of IL-1Ra mRNA (1.9-fold induction) whereas pretreatment of non
      transfected cells did not block induction of IL-1Ra mRNA (21.6-fold induction,
      P<0.02 compared with stimulated transfected cells without alpha-amanitin). These
      findings demonstrate that Ntcp may be an important mediator of alpha-amanitin
      uptake by the liver.

PMID- 14598022
TI  - Alteration of pituitary hormone-immunoreactive cell populations in rat offspring
      after maternal dietary exposure to endocrine-active chemicals.
AB  - We previously performed dose-response studies of genistein, diisononyl phthalate,
      4-nonylphenol, methoxychlor (MXC), and bisphenol A to examine the impact of
      maternal dietary exposure from gestational day 15 to postnatal day 10 on the
      development of rat reproductive system in later life. Among the chemicals MXC
      alone showed typical estrogenic effects only at the maternally toxic 1200 ppm.
      The present study was performed to examine the sensitivity of immunohistochemical
      analysis of pituitary cells of offspring similarly exposed to each chemical for
      detection of endocrine-disrupting effects. For this purpose, ratios of pituitary
      cells expressing luteinizing hormone (LH), follicle stimulating hormone (FSH) and
      prolactin (PRL), were measured at 3 and 11 weeks of age. Ethinylestradiol (EE) at
      0.5 ppm was used as a reference chemical. At week 3, decrease in the relative
      proportions of LH, FSH, and PRL cells in males and LH cells in females was
      evident with MXC at 1200 ppm. At week 11, increase was found for PRL cells from
      240 ppm MXC, and FSH cells at 1200 ppm in females. On the other hand, EE
      increased the PRL cell percentage in females at week 3 but no effects were
      apparent at week 11. The other chemicals were without influence at either time
      point. The results suggest that the assessment of the pituitary cell populations
      might be a more sensitive approach to detect perinatal endocrine-disrupting
      effects than other methods. The difference in the pituitary effect between MXC
      and EE is discussed.

PMID- 14598023
TI  - Neurobehavioural test results and exposure to inorganic mercury: in search of
      dose-response relations.
AB  - The aim of the analysis was, in general, to find a way to summarise results of
      studies in search of exposure-response relationships and, in particular, to ask
      whether an exposure-response relationship can be ascertained for neurobehavioural
      studies on occupational mercury exposure. Eighteen studies dealing with human
      mercury exposure and examining 1,106 exposed and 1,105 control subjects were
      included in the analysis. Effect sizes were calculated for each of the single
      neuropsychological test results on cognitive and motor performance and were
      considered in relation to mean current concentrations of exposure. The total of
      effect sizes demonstrated a correlation to exposure in the range of r=0.50.
      Additional analyses showed that the influence of mercury on psychological
      functions was different and that results on motor performance compared with
      memory and attention revealed the greatest impairment in mercury-exposed workers.
      Implications for the reversibility of impairments could be discussed because
      three of the studies examined subjects whose exposure had ceased. Besides the
      usefulness of the approach, it became obvious that the available 18 studies are a
      small sample, even when non-dimensional effect-sizes are used; hence, not all
      psychological domains covered by tests could be analysed.

PMID- 14598024
TI  - Radiocalcium absorption is reduced in postmenopausal women with vertebral and
      most types of peripheral fractures.
AB  - Intestinal calcium absorption accounts for 60% of the variance in calcium balance
      and is therefore a potentially very important determinant of bone status. Whether
      measured by the balance technique or with radiocalcium, it is known to be
      significantly reduced in postmenopausal women with vertebral and hip fractures.
      By contrast, there is very little information about calcium absorption in other
      types of postmenopausal fracture. We now report a series of 549 untreated,
      Caucasian postmenopausal women in whom we recorded prevalent fractures, measured
      radiocalcium absorption, and obtained radiographs of the lateral thoracic and
      lumbar spine. Of these women, 172 had no prevalent fractures, showed normal spine
      radiographs, and served as controls; 72 had one or more peripheral fractures but
      normal spine radiographs; 147 had one or more wedged or crushed vertebrae but no
      peripheral fractures; and 158 had a history of peripheral fracture and one or
      more fractured vertebrae. Age-adjusted radiocalcium absorption was significantly
      lower in the two groups with spinal fractures than in the controls ( P<0.001) but
      not in the group with peripheral fractures only. It was also lower in the cases
      with more than two spinal fractures than in those with two or less (P<0.001). In
      respect of peripheral fractures, the greatest age-adjusted absorption deficit was
      found in fractures of the humerus (35%) followed by hip (32%), spine (21%), wrist
      (19%), and rib 17% (all significant but not significantly different from each
      other). Lesser deficits in tibia, ankle and foot fractures were not significant
      but type 2 errors could not be excluded. We conclude that impaired calcium
      absorption is particularly associated with those fractures for which osteoporosis
      is a significant risk factor.

PMID- 14598025
TI  - Two new regions of interest to evaluate separately cortical and trabecular BMD in
      the proximal femur using DXA.
AB  - To differentiate changes in trabecular and cortical bone density at a skeletal
      site bearing body weight, the main goal of this retrospective study was to
      develop and characterize two new regions of interest (ROIs) for DXA at the hip,
      one mainly focusing on trabecular bone and another mainly focusing on cortical
      bone. Specific aims were to maximize the precision of the ROIs and to
      characterize their usefulness for monitoring age-related bone loss and
      discriminating controls from fracture cases in a cross-sectional study population
      and to compare them with earlier ROIs designed by our group. The study used
      populations from two different previous studies conducted in our laboratory, with
      one comprising cohorts of healthy premenopausal women, healthy postmenopausal
      women, and postmenopausal osteoporotic women with at least one spinal fracture
      (Spine Fx Study) and the other one comprising two cohorts of age-matched
      postmenopausal women, in whom cases had sustained a hip fracture (Hip Fx study).
      The new ROI for trabecular bone (CIRCROI) tries to improve on the earlier custom
      designed Central ROI, which was also targeted at trabecular bone. CIRCROI
      consists of an approximate largest circle that can fit inside the femoral
      proximal metaphysis without touching the superior and inferior endocortical
      walls. The new ROI for cortical bone (CORTROI) at a site bearing body weight is
      defined as a horizontal rectangular box crossing the femoral shaft below the
      lesser trochanter. CORTROI BMD cohort means were significantly higher than all
      other ROIs, and CIRCROI BMD cohort means were lower than standard ROIs with the
      exception of Ward's ROI. CIRCROI BMD was highly correlated with total femur BMD (
      r=0.94) and Central BMD ( r=0.93), whereas CORTROI BMD correlations were lower
      (highest with total femur BMD ( r=0.86)). Fracture discrimination odds ratios
      (ORs) of all ROIs were significant for the Hip Fx Study, with CIRCROI BMD having
      the highest, and CORTROI BMD the lowest, OR (4.83 and 2.49 per SD, respectively,
      compared with 3.69 for Ward's ROI as the highest OR of standard ROIs). For the
      Spine Fx Study, only spinal and trochanteric BMD had significant OR. The new
      trabecular ROI had good short-term precision, comparable to the standard ROIs at
      the hip, but improving on that of Ward's triangle, the only standard ROI only
      including the anterior and posterior cortical walls and therefore more
      predominantly consisting of trabecular bone than other standard ROIs. The
      precision of the new cortical ROI was lower than standard DXA ROIs, except for
      Ward's triangle, but provides unique information on purely cortical bone at a
      skeletal site bearing body weight.

PMID- 14598026
TI  - Excess mortality after hospitalisation for vertebral fracture.
AB  - An excess mortality is well described after vertebral fracture. Deaths are in
      part related to co-morbidity, but could also be due to the fracture event itself,
      either directly or indirectly. The aim of this study was to examine the quantum
      and pattern of mortality following vertebral fracture. We identified 16,051 men
      and women aged 50 years or more with a vertebral fracture that required
      hospitalization in 28.8 million person years from the patient register of Sweden.
      Mortality after vertebral fracture was examined using Poisson models applied to
      fracture patients and compared to that of the general population. At all ages,
      the risk of death was markedly increased immediately after the event. After a
      short period of declining risk, the risk increased with age at a rate that was
      higher than that of the general population and comparable to that 1 year after
      hip fracture. The latter function was assumed to be due to deaths related to co
      morbidity and the residuum assumed to be due to the vertebral fracture. Causally
      related deaths comprised 28% of all deaths associated with vertebral fracture
      (depending on age). We conclude that a minority of deaths following
      hospitalization for vertebral fracture are attributable to the fracture itself
      under the assumptions we used.

PMID- 14598027
TI  - Establishment of BMD reference plots and determination of peak BMD at multiple
      skeletal regions in mainland Chinese women and the diagnosis of osteoporosis.
AB  - Osteoporosis is a major public health problem, particularly in women. Bone
      mineral density (BMD) reference plot is a basic, and the peak BMD (PBMD) an
      important, parameter in the diagnosis of osteoporosis. In order to establish
      reference plots of BMD at multiple skeletal sites in Chinese women and improve
      the diagnostic accuracy for osteoporosis, we measured BMDs at several skeletal
      regions in 3,378 Chinese women, aged 5-96 years, using a dual-energy X-ray
      absorptiometry fan-beam bone densitometer. After determining that the cubic
      regression model best fit all skeletal regions, we utilized the curve-fitting to
      establish BMD reference plots and utilized the curve-fitting equation to
      calculate the highest BMDs at all skeletal regions using three different methods
      of calculation--actual PBMD (method A), PBMD of each 5-year age group (method B),
      and a cross-section of age (method C). When the three methods were compared, we
      found significant differences among them at the majority of skeletal regions
      studied. When we utilized these three methods to determine the prevalence of
      osteoporosis in 2,120 women aged 40 years and older, except for the Ward's
      triangle, we observed significant differences among them at all skeletal regions.
      In the present study, we established new BMD reference plots at multiple skeletal
      regions for women of mainland China. Our findings also indicate that curve
      fitting equations can be employed to calculate actual PBMDs specific to
      individual regions, and that the use of different methods to calculate PBMD may
      have a significant impact on both PBMD and the diagnosis of osteoporosis.
      Therefore, we suggest that a standardized method be established to calculate site
      specific PBMDs based on the peak values of best-fit reference curves in
      appropriate age groups.

PMID- 14598028
TI  - Follow-up after intensive care: a single center study.
AB  - OBJECTIVES: To study health problems, quality of life, functional status, and
      memory after intensive care. SETTING: Adult patients ( n=346) discharged from a
      university hospital ICU. DESIGN AND METHODS: Prospective cohort study. Follow-up
      patients were found using the ICU database and the Peoples Registry. Quality of
      life (QOL) was measured with the Short Form 36 (SF-36) 6 months after ICU
      discharge. Semi-structured interviews, questionnaires, Glasgow Outcome Score
      (recovery), and Karnofsky Index (functional status) were used at consultations 7
      8 months after ICU discharge. RESULTS: The SF-36 response rate was 64.5%, with
      scores significantly lower than population scores. Consultation patients ( n=136)
      did not differ from the rest ( n=210) regarding age, SAPS II scores, length of
      stay (LOS), and reasons for ICU admission. At follow-up 67.6% of consultation
      patients continued most activities, 75% looked after themselves, and 64.7% were
      non-workers, compared to 40.4% before the ICU admission. During and after the ICU
      stay, 40% lost more than 10 kg body weight. Fifty-eight (43%) could not remember
      anything from their ICU stay. At follow-up only 22 (16%) could remember having
      received information during their ICU stay. Three patients needed referral to
      other specialties. CONCLUSIONS: We should focus more on optimizing symptom
      management and giving repeated information after ICU discharge. Nutritional
      status and weight loss is another area of concern. More research is needed to
      find out how the broad range of psychosocial and physical problems following an
      ICU stay relates to the stay.

PMID- 14598029
TI  - Comparison of three severity scores for critically ill cancer patients.
AB  - OBJECTIVE: To compare three scoring systems, the Acute Physiology and Chronic
      Health Evaluation (APACHE) II, the Simplified Acute Physiology Score (SAPS) II
      and a modified Mortality Probability Model II (ICU cancer mortality model, ICMM)
      for their prognostic value for mortality during hospital stay in a group of
      cancer patients admitted to a medical ICU. DESIGN: Prospective cohort study.
      SETTING: Medical ICU of a tertiary care hospital. PATIENTS: Two hundred forty-two
      consecutive cancer patients admitted to the ICU. MEASUREMENTS AND RESULTS:
      Variables included in APACHE II, SAPS II and the ICMM scores as well as
      demographic data were assessed during the first 24 h of stay in the ICU. Hospital
      mortality was measured; it was 44%. Calibration for all three scoring systems was
      acceptable, SAPS II yielded a significantly superior discrimination between
      survivors and non-survivors. The areas under the receiver operating
      characteristic curves were 0.776 for APACHE II, 0.825 for SAPS II and 0.698 for
      the ICMM. CONCLUSION: The SAPS II was superior to APACHE II and ICMM. The newly
      developed ICMM does not improve mortality prediction in critically ill cancer
      patients.

PMID- 14598031
TI  - A new approach to extending the wheat marker pool by anchored PCR amplification
      of compound SSRs.
AB  - A study was undertaken to determine the utility in bread wheat of anchored PCR
      for the development of single locus SSR markers targeted at compound repeat
      motifs. In anchored PCR, microsatellite amplification is achieved using a single
      primer complementary to the flanking sequence, and one which anchors to the
      repeat junction of the compound SSR. The recovery rate of useable markers was
      found to be similar (43%) to that reported for conventionally generated SSRs.
      Thus, anchored PCR can be used to reduce the costs of marker development, since
      it requires that only half the number of primers be synthesised. Where
      fluorescence-based platforms are used, marker deployment costs are lower, since
      only the anchoring primers need to be labelled. In addition, anchored PCR
      improves the recovery of useful markers, as it allows assays to be generated from
      microsatellite clones with repeat sequences located close to their ends, a
      situation where conventional PCR amplification fails as two flanking primers
      cannot be designed. Strategies to permit the large-scale development of compound
      SSR markers amplified by anchored PCR are discussed.

PMID- 14598030
TI  - Effect of thalidomide and rosiglitazone on the prevention of diabetic retinopathy
      in streptozotocin-induced diabetic rats.
AB  - AIMS/HYPOTHESIS: Our aim was to compare the therapeutic effect of thalidomide and
      rosiglitazone on the prevention of diabetic retinopathy in streptozotocin-induced
      diabetic rats. METHODS: Male Holtzman rats of 6 to 8 weeks of age and weighing
      170+/-30 g were randomly divided into four groups: control ( n=13), untreated
      diabetic ( n=17) and diabetic rats treated with thalidomide (200 mg kg(-1) day(
      1)) ( n=8) or rosiglitazone (1 mg kg(-1) day(-1)) ( n=22) for 3 months. Diabetes
      was induced by streptozotocin with the rats having a body weight of 70 mg/kg.
      After treatment, vascular endothelial growth factor (VEGF) concentrations in
      ocular fluid were compared between the different groups, and retinal capillary
      basement membrane thickness was measured by electron microscopy. RESULTS: Higher
      VEGF concentrations in ocular fluid and thicker basement membranes were observed
      in untreated diabetic rats compared to the control rats. Similar VEGF
      concentrations and basement membrane thickness were observed for the thalidomide
      treated group compared with the control group, whereas no difference in these
      parameters was observed between the rosiglitazone-treated rats and the control or
      untreated diabetic rats. CONCLUSIONS/INTERPRETATION: Our findings confirm the
      association between VEGF concentrations and diabetic retinopathy as suggested by
      other investigators. Thalidomide, but not rosiglitazone, was associated with the
      inhibition of basement membrane thickening and the blockade of the increase of
      VEGF in ocular fluid, thus representing a potential therapeutic drug for the
      prevention of diabetic retinopathy.

PMID- 14598032
TI  - [Current aspects of attachment theory and development psychology as well as
      neurobiological aspects in psychiatric and psychosomatic disorders].
AB  - This review covers basic principles of attachment research and its relationship
      to and implications for psychiatric and psychosomatic disorders. A great number
      of studies deal with the importance of attachment theory in the development of
      these disorders associated with distinct attachment styles. The most well-known
      concept is the attachment theory created by John Bowlby (1907-1990), which has
      strengthened our knowledge on early mother-infant relationships and influenced
      guidelines for child care. Within this concept, family structure is of great
      importance for the psychological development of the child and later the adult.
      Attachment research indicates that disturbances of patients with psychosomatic,
      e.g., somatoform disorders, in establishing relations must be seen in a
      developmental genetic context. A model of vulnerability is introduced which
      describes the development of psychopathology concerning the formation of
      representations taking advantage of attachment theory. Additionally, recent
      progress in cognitive neurosciences addresses attachment theory. During the last
      decade, neurobiological studies in rodents, primates, and humans indicate that
      early influences of psychosocial factors could have permanent consequences for
      brain structure and function. Besides the psychoanalytical and behavioral view
      concerning psychiatric and especially psychosomatic disorders, the integration of
      neurobiological findings will be a major challenge for the generation of further
      concepts.

PMID- 14598033
TI  - [Personality disorders and psychopathology following trauma. Reflection on
      diagnostic classification].
AB  - Pervasive personality disorders have been shown to be long-term sequelae of
      cumulative childhood physical and sexual traumatization. This finding is not
      reflected in DSM-IV and ICD-10 classifications where post-traumatic stress
      disorder is confined to intrusions, avoidance, numbing, and hyperarousal.
      However, there is growing evidence that trauma etiology should be taken into
      account in planning treatment for personality disorders. It is not yet clear
      whether childhood traumatization is more strongly associated with borderline
      personality disorder than with other personality disorders. The finding of a
      substantial overlap between borderline personality disorder and dissociative
      identity disorder gives rise to discussions concerning the relationship of these
      two pathologies.

PMID- 14598034
TI  - [The German version of the Structured Inventory of Malingered Symptomatology:
      SIMS].
AB  - The current article addresses the psychometric qualities of the German version of
      the Structured Inventory of Malingered Symptomatology (SIMS), a self-report
      measure of malingering. The SIMS was administered to a heterogeneous sample of
      forensic patients (n=62) and undergraduate students (n=204). Within the student
      sample, some undergraduates were instructed to feign certain pathological
      conditions, while others were asked to respond honestly to the SIMS items. The
      findings indicate that the German version of the SIMS demonstrates adequate test
      retest stability and internal consistency. In the patient sample, the SIMS was
      found to correlate strongly with manipulative and antisocial personality
      features. More specifically, SIMS scores were higher in sexually delinquent
      patients with antisocial personality disorders. Our findings support the SIMS as
      a valuable screening tool for malingering of psychiatric symptoms.

PMID- 14598035
TI  - [Reliability and validity of the Wender-Utah-Rating-Scale short form.
      Retrospective assessment of symptoms for attention deficit/hyperactivity
      disorder].
AB  - The diagnosis of adult attention deficit/hyperactivity disorder (ADHD) requires
      the retrospective assessment of ADHD symptoms in childhood. The Wender Utah
      Rating Scale (WURS) is helpful in detecting ADHD-associated symptomatology in
      childhood. A German short version (WURS-k) of this instrument has been made
      available recently. In the present study, we investigated the validity of the
      WURS-k. In a population of 63 adult ADHD patients (according to ICD-10 and DSM-IV
      criteria) and 1,303 male controls, ROC analysis indicated a sensitivity of 85%
      and specificity of 76% at a cutoff of 30 points. In ADHD patients, seven
      individual factors explained 70.3% of the variance. The highest diagnostic
      precision was demonstrated using the WURS-k total score. The seven extracted
      factors of the WURS-k did not differ in diagnostic value. Significant
      correlations were found between impulsivity according to Eysenck's Impulsivity
      Questionnaire (EIQ) and excitability, aggression, emotional lability, and
      satisfaction on the Freiburg Personality Inventory (FPI-R) in ADHD patients.
      Concerning a 30-50% persistence of ADHD symptomatology in adults, these
      correlations underline the diagnostic validity of the WURS-k. The scale
      manifested excellent internal consistency (alpha=0.91) and a split-half
      correlation of r(12)=0.85.

PMID- 14598036
TI  - [Adaptive indication in outpatient psychodynamic short-term psychotherapy.
      Results of a prospective naturalistic research study].
AB  - Health care insurers in Germany fund long-term psychotherapy of up to 240
      sessions as well as brief psychotherapeutic interventions of up to 25 sessions.
      In a former study, it was observed that a substantial proportion of interventions
      initially designed as brief psychotherapy were changed into long-term therapy.
      The present study investigated the criteria of such decisions to change treatment
      plans and is part of a more comprehensive auditing study in outpatient
      psychotherapy. Twenty-six psychotherapists in private practice participated in
      the study. During a 12-month recruitment period, 70 patients started with brief
      psychodynamic psychotherapy. Thirty-six therapies were evaluated according to the
      study protocol. The results provide evidence that motivation for psychotherapy,
      satisfaction with the results of therapy, persistence of psychological symptoms
      at the end of short-term intervention, and aspects of the patient's personality
      are factors predictive of treatment selection. Patients who changed from short
      term to long-term therapy were more motivated towards their therapy (prognostic
      indication), displayed more severe symptoms, were less satisfied with the results
      of short-term psychotherapy (adaptive indication), and scored higher on the
      "structure of personality organization" parameter according to the OPD diagnostic
      system.

PMID- 14598037
TI  - [Categorical and dimensional assessment of "psychopathy" in German offenders.
      Prevalence, gender differences and age factors].
AB  - The personality construct "psychopathy" is of utmost importance in legal
      prognosis. In the last 20 years, a multitude of empirical research proved the
      predictive validity of this concept concerning the degree of dangerousness
      represented by an offender. In the present study, a representative, nonselected
      sample of 416 offenders was examined using the Screening Version of the
      Psychopathy Checklist (PCL:SV). The data were analysed both categorically and
      dimensionally according to the three-factor model proposed by Cooke and Michie.
      In comparison to North American Studies the prevalence of high scorers was
      significantly lower, implicating intercultural differences. Analyses of the
      effects of gender yielded higher scores on each of the three factors in male
      offenders. Concerning different age cohorts, it turned out that the arrogant and
      deceitful interpersonal style and deficient affective experience remained stable,
      whereas the impulsive and irresponsible behavioral style decreased with
      increasing age. Therefore, our results point out intercultural differences
      already shown in the prevalence of "psychopathy" and confirm the effects of
      gender and age concerning this construct.

PMID- 14598038
TI  - [A case of delirium after olanzapine intoxication].
AB  - We describe a case of delirium due to olanzapine overdose. After ingestion of 280
      mg of olanzapine, a 19-year-old schizophrenic patient developed a delirium (ICD
      10: F 05.0) with consciousness disturbance, disorientation in time, space, and
      situation, acoustic and visual hallucinations, and agitation. The symptoms lasted
      for approximately 36 h. Blood pressure, temperature, and heart frequency showed
      no disturbance. There were no abnormalities in ECG, EEG, or routine blood tests.
      Approximately 36 h after the intoxication, the patient recovered fully. Until
      now, there have been no reports of delirium from this cause.

PMID- 14598039
TI  - [Organic schizophreniform disorder with pre-existing autoimmune thyroiditis].
AB  - We report the case of a 63-year-old patient with sudden onset of an acute
      syndrome of auditory hallucinations and delusions. Considering the anamnesis,
      course of the illness, and organopathologic results, we assumed an organic
      schizophreniform disorder within the scope of pre-existing autoimmune
      thyroiditis. Under treatment with high-potency neuroleptics, we observed partial
      regression and, after strumectomy, complete regression of the psychotic symptoms.
      Apparently, the acute organic schizophreniform disorder was caused by a changed
      metabolic situation with a transition to hyperthyroidism coinciding with
      beginning a small dose of antithyroid drugs.

PMID- 14598040
TI  - [Hyponatraemic delirium as an early symptom of small-cell bronchial carcinoma].
AB  - In the psychiatric clinic, delirious states are rare as the first symptoms of
      paraneoplastic syndrome, and the aetiology can only be clarified by consequent
      differential diagnostic efforts. We report the case of a 49-year-old man who was
      admitted to our psychiatric unit with delirium. Laboratory investigations showed
      hyponatraemia, serum hypo-osmolality, and urine hyperosmolality characterising
      the syndrome of inappropriate antidiuresis (SIADH). As a paraneoplastic syndrome,
      SIADH is most frequently associated with small-cell lung cancer (SCLC). Whereas
      chest X-ray was negative, chest CT scan and bronchoscopy including histology
      revealed a SCLC at an early stage of limited disease. Early oncological therapy
      made it possible for our patient to return to work with a satisfactory quality of
      life. Twenty-one months after first admission, he died as a result of recurrent
      SCLC metastases.

PMID- 14598041
TI  - [Morita therapy--a Japanese method for treating neurotic anxiety syndrome].
AB  - In Japan, the traditional Morita therapy is indicated for "shinkaishitsu"
      personalities, i.e., patients with neurotic anxiety disorder, especially with
      phobic and hypochondriac symptoms. The substantial theoretical basis and
      therapeutic principles were taken from Zen Buddhism, such as the development of
      the ego in the "space" between subject and object, the unity of body and soul,
      the distinction of inner and outer nature, and the principles of emptiness and
      nothingness. The treatment consists of an initial 7-day period of strict and
      isolated rest in bed followed by step-by-step occupational therapy and final
      reintegration into job and family. The founder of this therapy, Morita, sees the
      healing of the patients not in the removal of their fears but in the inner
      acceptance (arugamama) of the fears they have experienced--corresponding to an
      essential principle in Zen Buddhism. Nowadays, the method is used in a modified
      form adjusted to the change in mentality of Japanese patients.

PMID- 14598042
TI  - [The present status of Japanese psychopathology. A summary of the World Congress
      of Psychiatry in Yokohama].
AB  - The last World Congress of Psychiatry took place in Yokohama, Japan. It gave the
      opportunity for presenting specifically Japanese approaches to psychopathology to
      the international psychiatric community. This paper reports on prominent trends
      in Japanese psychopathological research, which has close ties to German
      psychopathology

PMID- 14598043
TI  - [Alfred Doblin (1878-1957). Notes on the cover picture].
AB  - Alfred Doblin studied medicine after completing his Abitur (A-levels). In 1905 he
      earned his doctorate under Alfred Hoche, director of the psychiatric clinic, by
      presenting a study on "Memory disorders in Korsakoff's psychosis." He
      subsequently worked as an assistant doctor in various psychiatric clinics until
      he switched to internal medicine in 1908. He opened a practice as panel doctor in
      1911, which he operated until 1930. Although Doblin had already published a few
      stories, he first became generally known in 1929 with the appearance of his novel
      entitled "Berlin Alexanderplatz: the story of Franz Biberkopf." After the burning
      of the Reichstag in February 1933, as a Jewish socialist Doblin was forced to
      emigrate. He was unable to work as a physician during his exile, but remained
      active in his literary pursuits. Doblin died on 26 June 1957 in the state
      hospital in Emmendingen.

PMID- 14598044
TI  - Clinical and serological associations of autoantibodies to GW bodies and a novel
      cytoplasmic autoantigen GW182.
AB  - A novel autoantigen named GW182 was recently identified when the serum from a
      patient with a sensory ataxic polyneuropathy was used to immunoscreen a HeLa cDNA
      library. Unique features of the GW182 protein include 39 repeats of glycine (G)
      and tryptophan (W) residues, binding to a subset of messenger RNA and
      localization to unique structures within the cytoplasm that were designated GW
      bodies (GWBs). The goal of the present study was to identify the clinical
      features of patients with anti-GW182 antibodies and to characterize the B cell
      anti-GW182 response by defining the epitopes bound by human autoantibodies. The
      most common clinical diagnosis of patients with anti-GW182 antibodies was
      Sjogren's syndrome followed by mixed motor/sensory neuropathy, and systemic lupus
      erythematosus. Of interest, 5 (28%), 9 (50%), and 3 (17%) of the 18 sera that
      react with GWBs had autoantibodies to the GW182 and the 52 kDa and 60 kDa SS-A/Ro
      autoantigens, respectively. Epitopes bound by the human autoantibodies were
      mapped to the GW-rich middle part of the protein, the non-GW rich region, and the
      C-terminus of GW182 protein. None of the GW182 epitopes had significant sequence
      similarities to other known proteins. GW182 represents a new category of
      ribonucleoprotein autoantigens.

PMID- 14598046
TI  - Mechanisms of action of intravenous immunoglobulin in autoimmune and inflammatory
      diseases.
AB  - Intravenous immunoglobulins (IVIg) exert a broad range of immunoregulatory
      functions that provide a basis for the beneficial effects of IVIg in autoimmune
      and systemic inflammatory disorders. This review focuses on the effects f IVIg on
      humoral and cellular immunity that may be of relevance for the treatment of
      inflammatory neurological diseases.

PMID- 14598045
TI  - Using pharmacogenetics and pharmacogenomics in the treatment of psychiatric
      disorders: some ethical and economic considerations.
AB  - Current pharmacotherapies for psychiatric disorders are generally incompletely
      effective. Many patients do not respond well or suffer adverse reactions to these
      drugs, which can result in poor patient compliance and poor treatment outcome.
      Adverse drug reactions and non-response are likely to be influenced by genetic
      polymorphisms. Pharmacogenetics holds some promise for improving the treatment of
      mood disorders by utilising information about genetic polymorphisms to match
      patients to the drug therapy that is the most effective with the fewest side
      effects. Pharmacogenomics promises to facilitate the development of new drugs for
      treatment. However, these technologies raise many ethical, economic and
      regulatory issues that need to be addressed before they can be integrated into
      psychiatry, and medicine more generally. We discuss ethical and policy issues
      arising from pharmacogenetic testing and pharmacogenomics research, such as
      informed consent, privacy and confidentiality, research on vulnerable persons and
      discrimination; and economic viability of pharmacogenetics and pharmacogenomics.
      We conclude with recommendations for the regulation and distribution of
      pharmacogenetic testing services and pharmacogenomic drugs.

PMID- 14598047
TI  - Intravenous immunoglobulins in neurological disorders: safety issues.
AB  - IVIg products may be applied for the provision of antibodies in patients with
      primary or secondary antibody deficiency syndromes or with the aim of immune
      modulation in patients with autoimmune diseases. The average dose for the
      provision of antibodies is 400 mg/kg per month while much higher doses are needed
      1 to 2 g/kg in a single or in repeated occasions in the treatment of autoimmune
      diseases e. g. neurological diseases. Indications for treatment have been
      specified at two consensus meetings (1990 and 1999) and by different groups of
      experts but off-label use highly exceeds the recommended indications. For this
      reason risk benefit assessment is of great importance. Adverse events can be
      categorized as (1) early inflammatory, (2) infectious, (3) rare complications of
      (mainly) high dose treatment. Early inflammatory reactions are known since the
      initiation of immunoglobulin treatment, the rate varies greatly 10%-85% and
      reactions can usually be dealt with by lowering the infusion rate. Viral
      infections e. g. transmission of viral hepatitis by IVIg have been a problem in
      certain products until the mid-1990s and industry responded in a fast and
      efficient manner. Viral safety has been achieved and all IVIg products licensed
      are considered to be safe in this respect. Rare complications mainly of high dose
      treatment: renal complications were described already in the mid-1980s they were
      mainly but not only linked to products containing sucrose, maltose and glucose
      with or without glycine. These complications are rare (88 patients reported in 30
      years) and older patients and patients with conditions predisposing to renal
      disease were at increased risk. Thromboembolic events were another rare but
      severe complication of high dose treatment also associated with rapid infusion,
      deep venous thrombosis, pulmonary embolism, myocardial infarction and stroke have
      been reported. Possible mechanisms have been discussed.

PMID- 14598048
TI  - Treatment of multiple sclerosis with intravenous immunoglobulin: review of
      clinical trials.
AB  - Intravenous immunoglobulin (IVIG) is an established therapy for a number of
      neuroimmune disorders, including Guillain-Barre syndrome and chronic inflammatory
      demyelinating polyneuropathy. IVIG exerts a number of effects that may be
      beneficial in multiple sclerosis (MS): reduction of inflammation, inhibition of
      macrophages, and promotion of remyelination. Four double-blind trials have been
      performed of IVIG in relapsing-remitting MS. A meta-analysis of the four trials
      has shown that IVIG reduces the relapse rate, new MRI lesions, and disease
      progression. IVIG does not seem to be of any benefit in chronic visual or motor
      symptoms in MS. In secondary progressive MS, IVIG has not shown effect on disease
      progression, relapses or new MRI lesions. In conclusion, IVIG is an alternative
      second-line treatment to approved therapies in relapsing-remitting MS, but the
      ideal dosage of IVIG still needs to be determined.

PMID- 14598049
TI  - Antibodies and myelination: facts and misacts.
AB  - Polyreactive (auto)antibodies are frequently found in healthy subjects and are
      bona fide considered to be nonpathogenic. However, autoreactive B cells and
      circulating (auto)antibodies have been associated with several neurological
      syndromes, including demyelinating disorders. Whether these antibodies can have a
      real impact on disease development is still a matter of debate. Here, we briefly
      summarize some of the most recently published data on both the deleterious and
      the protective effects of antibodies in autoimmune demyelinating disorders of the
      central nervous system.

PMID- 14598050
TI  - Immunoglobulin treatment of multiple sclerosis: future prospects.
AB  - In one of the most frequent MS demyelination patterns, IgG and complement are
      demonstrable on myelin surface. It is, probably, an antibody-mediated pattern of
      myelin damage, usually associated with acute MS, but, at times, observed even in
      chronic cases. This pattern of myelin damage is extremely similar to that
      observed in acute demyelinating inflammatory polineuropathies, such as Guillain
      Barre syndrome, and in acute disseminated encephalomyelitis (ADEM), a rare
      demyelinating disease usually occurring after a viral infection or vaccination.
      These pathologies response well to IgG treatment. Although hyperacute severe
      cases of MS seem to respond well to IgG treatment, this does not seem the case
      for other cases of relapses in relapsing-remitting MS. Several trials failed to
      provide clear evidence of clinical and MRI efficacy of high-dose IgG parenteral
      treatment in relapsing-remitting multiple sclerosis (MS). The study of Confavreux
      and the PRIMS study showed that the relapse rate decreases significantly during
      pregnancy in MS patients, while increases after delivery. IgG is not a cytostatic
      drug and therefore it has been tested to see whether it reduces relapse
      occurrence after delivery. In pregnant MS patients treated with high dose, Haas'
      study and our experience noted a slight increase relapse rate during the six
      month after delivery but lower than that showed in Confavreux and PRIMS studies
      in untreated pregnant MS women.

PMID- 14598051
TI  - Rasmussen's syndrome.
AB  - Rasmussen's encephalitis (RE) is characterized by focal seizures, often
      associated with epilepsia partialis continua, progressive neurological
      deterioration, hemispheric atrophy, and inflammatory histopathology. Surgical
      exclusion of the affected hemisphere is the only treatment that halts progression
      of the disease. The possible role played by serum antibodies against the
      glutamate receptor GluR3 in the animal model and in a number of affected patients
      supports a disimmune component in the pathogenesis of the disease and provides a
      rational basis for considering the use of immunomodulatory treatments in selected
      cases. The use of intravenous immunoglobulins has produced encouraging results in
      adult-onset RE but further studies are needed to assess the effect, dosage, and
      schedules in childhood-onset RE.

PMID- 14598052
TI  - Infantile encephalopathies.
AB  - Many cases of drug-resistant infantile epilepsy (West syndrome, Lennox-Gastaut
      syndrome, Landau-Kleffner syndrome, severe myoclonic epilepsy, and Rasmussen's
      encephalitis) were found to respond in some measure to treatments with
      intravenous immunoglobulins (IVIG), but relapses were common. However, as the
      side effects of IVIG infusion are insignificant, it is better not to deny
      treatment of epileptic encephalopathies to patients who have been treated
      unsuccessfully even with new anti-epileptic drugs.

PMID- 14598053
TI  - Immunoglobulins in chronic inflammatory demyelinating polyneuropathy.
AB  - This article reviews the efficacy and tolerability of intravenous immunoglobulins
      (IVIg) in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP),
      including those forms associated with monoclonal gammopathy (paraproteinemic
      demyelinating neuropathy, PDN). Class I trials demonstrated that IVIg are
      effective in CIDP. About two-thirds of patients respond to initial treatment;
      however, most of them require repeated drug doses to maintain improvement. For
      PDN there are some evidences that IVIg are efficacious; however, it seems that
      less than 50% of the patients respond to this treatment and the persistence of
      the response over time has not been thoroughly investigated. The safety profile
      of immunoglobulins is generally good; however, the possibility of the occurrence
      of serious adverse effects should always be considered before starting treatment.

PMID- 14598054
TI  - Treatment of multifocal motor neuropathy.
AB  - Multifocal motor neuropathy (MMN) is a purely motor multineuropathy characterized
      by multifocal conduction blocks on motor nerves. The pathogenesis of MMN is not
      known but its frequent association with anti-ganglioside antibodies and the
      improvement after immune therapies support an immune pathogenesis. Patients with
      MMN do not respond to steroids or plasma exchange, which may occasionally even
      worsen the symptoms, while the efficacy of other immune suppressive therapies is
      controversial. More than 80% of MMN patients rapidly and consistently improve
      with highdose intravenous immunoglobulin (IVIg), the efficacy of which has been
      confirmed in four controlled studies. In most patients, however, the effects of
      this therapy only last a few weeks and improvement has to be maintained with
      periodic infusions for long periods of time, if not indefinitely.

PMID- 14598055
TI  - High-dose intravenous immunoglobulin in inflammatory myopathies: experience based
      on controlled clinical trials.
AB  - Controlled clinical trials with high-dose intravenous immunoglobulin (IVIg) have
      been conducted in patients with DM and IBM, but not PM. A double-blind placebo
      controlled study in DM patients, resistant or partially responsive to
      conventional therapies, showed that IVIg is very effective in improving both the
      muscle strength and the skin rash. The clinical benefit, which was impressive in
      patients with early disease, was associated with improvement in the muscle
      cytoarchitecture. Quantitative histological studies in repeated muscle biopsies
      showed a statistically significant increased in the size of muscle fibers and the
      number of capillaries with normalization of the capillary diameter. Resolution of
      the aberrant immunopathological parameters including interception of complement
      activation products and downregulation of T cells, ICAM-I, VCAM, TGF-beta and MHC
      I molecules was also noted. In IBM, IVIg showed marginal, and non statistically
      significant, improvements in muscle strength. Up to 20% of patients however,
      demonstrated clinical improvement with increased activities of daily living while
      certain muscle groups, such as the muscles of swallowing, showed significant
      improvements compared to placebo implying mild regional benefits. In PM, small
      uncontrolled series have shown improvements in muscle strength in up to 70% of
      the IVIg-treated patients. Because PM, as a stand-alone clinical entity, is a
      very rare disease, completion of controlled trials will be very difficult.

PMID- 14598056
TI  - Myasthenia gravis and myasthenic syndrome.
AB  - Myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS) are
      autoimmune ion channel disorders mediated by antibodies to postsynaptic
      acetylcholine receptors and presynaptic voltage-operated calcium channels,
      respectively. MG and LEMS are currently treated with corticosteroids and
      immunosuppressive drugs with a positive clinical outcome. Since both diseases are
      mediated by circulating autoantibodies, they are good candidates for
      immunomodulation by intravenous immunoglobulins (IVIG). Standardized controlled
      studies are lacking in this field, but there is general agreement that IVIG are
      effective. They can be used as an acute treatment to control temporarily the most
      severe forms of these diseases, as well as a chronic immunomodulating therapy in
      addition to standard pharmacological treatment. Several aspects of IVIG
      administration, cost benefit-analysis, and comparison to plasmapheresis are still
      needed.

PMID- 14598057
TI  - Creutzfeldt-Jakob disease associated with high titer of antithyroid
      autoantibodies: case report and literature review.
AB  - Hashimoto's encephalopathy and Creutzfeldt-Jakob disease (CJD) often have similar
      clinical features and may be confused, especially at onset. A 61-year-old woman
      developed rapidly progressive ataxia, myoclonus and dementia, with abnormalities
      seen on electroencephalography (EEG). Serum analysis disclosed high titers of
      antithyroid autoantibodies. Both clinical course and autopsy led to a definitive
      diagnosis of CJD. This case and a literature review of previous cases confirm
      that CJD may be confused with Hashimoto's encephalopathy. EEG, clinical and
      laboratory findings (including the positivity of 14.3.3 protein in the
      cerebrospinal fluid) are not conclusive for a differential diagnosis, especially
      at early stages. Only the results of genetic exams can allow a definitive
      diagnosis in a small percentage of cases while patients are still alive. In
      patients with unclear symptomatology and rapid onset of myoclonus, dementia and
      ataxia, the presence of antithyroid antibodies should be examined. If their
      levels are abnormal, corticosteroid therapy remains mandatory.

PMID- 14598058
TI  - A possible case of unruptured middle cerebral artery aneurysm presenting as
      epileptic seizures.
AB  - We report the case of a 73-year-old man with an unruptured aneurysm of the left
      middle cerebral artery. The initial sign was complex partial seizures. A standard
      scalp electroencephalogram was normal while neuropsychological tests revealed a
      slight deficit of episodic memory. Brain MRI showed an aneurysm at the left
      middle cerebral artery bifurcation. Cerebral angiography confirmed the presence
      of a saccular aneurysm at the left middle cerebral artery bifurcation, with a
      maximum diameter of 12 mm. This case had two main characteristic features:
      seizures had a quite late onset and were the only symptom the patient
      experienced.

PMID- 14598059
TI  - Sildenafil and transient global amnesia.

PMID- 14598060
TI  - 123I-Ioflupane/SPECT binding to striatal dopamine transporter (DAT) uptake in
      patients with Parkinson's disease, multiple system atrophy, and progressive
      supranuclear palsy.
AB  - We used SPECT and the tracer (123)I-Ioflupane to measure dopamine transporter
      (DAT) binding in the caudate nucleus and the putamen of 70 patients with
      Parkinson's disease (PD), 10 with multiple system atrophy (MSA-P type), and 10
      with progressive supranuclear palsy (PSP). Data were compared with 12 age-matched
      control subjects. We found significant reductions in mean striatal values in all
      three forms of parkinsonism. However, decrements were significantly greater in
      PSP (0.51+/-0.39, p<0.01) compared with MSA-P (0.70+/-0.33) and PD (0.95+/-0.38).
      No differences were found between MSA and PD. Putamen/caudate ratios were greater
      in PSP (0.83+/-0.12, p<0.01) than in PD (0.51+/-0.11), suggesting a more-uniform
      involvement of dopamine nerve terminals in both caudate nucleus and putamen. Our
      results confirm that DAT binding can provide an accurate and highly sensitive
      measure of dopamine degeneration. PSP patients may show a different pattern of
      neuronal loss compared with MSA and PD.

PMID- 14598061
TI  - Brain flow changes before and after deep brain stimulation of the subthalamic
      nucleus in Parkinson's disease.
AB  - Deep brain stimulation (DBS) of the subthalamic nucleus (STN) markedly improves
      motor symptoms and reduces medication needs in Parkinson's disease (PD) patients.
      However, its effect on brain function has remained unclear. We used SPECT and the
      tracer ECD to measure regional cerebral blood flow before and 6 months after DBS
      of the STN in 22 PD patients and 13 healthy controls. PD patients were divided
      into good and poor responders to DBS, if changes in "off" UPDRS motor scores
      after surgery were >60% or <40%, respectively. Statistical analysis was performed
      using the SPM99 software. At baseline, all PD patients showed significant
      perfusion reductions in cortical areas (premotor frontal, parietal, and
      occipital). After DBS, changes were normalized only in the good responders, while
      cortical defects in the poor responders were unchanged. No flow decrements were
      detected in basal ganglia and thalamus in both groups, suggesting that DBS does
      not have a "lesion-like" effect. We conclude that good surgery outcome is
      associated with normalization of cortical flow abnormalities in PD.

PMID- 14598062
TI  - Cognitive [correction of cognitve] estimation: comparison of two tests in
      nondemented parkinsonian patients.
AB  - The Time and Weight Estimation test (STEP) and the Cognitive Estimation Task
      (CET) are two recently devised tests for the assessment of cognitive estimation.
      In the present study, we compared their performance in 30 non-demented idiopathic
      parkinsonian (PD) patients, also evaluated with the Frontal Assessment Battery
      (FAB) as an index of executive impairment, with the aim of verifying the putative
      frontal circuitry of cognitive estimation processes. Six patients (20%) showed a
      pathological performance on either or both tests. After division of the PD sample
      into tertiles based on the FAB score, no significant difference was detected by
      either estimation test. Furthermore, the two questionnaires were unrelated to
      each other. Thus, deficits of cognitive estimation ability appear to be mild in
      PD without dementia and do not correlate with executive impairment. Unexpectedly,
      the CET and the STEP seem to have no unique underlying construct.

PMID- 14598063
TI  - Proteome analysis of mesencephalic tissues: evidence for Parkinson's disease.
AB  - Proteome analysis is a powerful methodology to investigate protein expression in
      tissues involved in diseases not linked to particular genetic defects. To date,
      this technique has a limited number of applications in the field of
      neurodegenerative disorders. We decided therefore to investigate by this approach
      autoptic mesencephalic tissues of patients with idiopathic Parkinson's disease as
      well as control specimens from healthy subjects.

PMID- 14598064
TI  - Effects of dopaminergic stimulation on peripheral markers of apoptosis: relevance
      to Parkinson's disease.
AB  - We investigated the effects of dopaminergic stimulation on anti-apoptotic protein
      Bcl-2, pro-apoptotic enzyme caspase- 3, and anti-oxidant/anti-apoptotic enzyme
      Cu/Zn superoxide dismutase (SOD) in human lymphocytes exposed to dopamine (DA).
      The same determinations were also carried out in parkinsonian patients treated
      with L-dopa. Caspase-3 activity and Cu/Zn SOD levels tended to increase when
      lymphocytes were exposed to low or intermediate doses of DA, while a decrease was
      observed, particularly in caspase-3 activity, with the higher DA dose. Bcl-2
      levels were unaffected. In patients, we observed a negative correlation between
      Cu/Zn SOD levels and daily intake of L-dopa, which also tended to be negatively
      correlated with caspase-3 activity, but not with Bcl- 2. Our results show that
      dopaminergic stimulation is associated with complex changes in regulatory
      proteins of apoptosis.

PMID- 14598065
TI  - DJ-1( PARK7), a novel gene for autosomal recessive, early onset parkinsonism.
AB  - Four chromosomal loci ( PARK2, PARK6, PARK7, and PARK9) associated with autosomal
      recessive, early onset parkinsonism are known. We mapped the PARK7 locus to
      chromosome 1p36 in a large family from a genetically isolated population in the
      Netherlands, and confirmed this linkage in an Italian family. By positional
      cloning within the refined PARK7 critical region we recently identified mutations
      in the DJ-1 gene in the two PARK7-linked families. The function of DJ-1 remains
      largely unknown, but evidence from genetic studies on the yeast DJ-1 homologue,
      and biochemical studies in murine and human cell lines, suggests a role for DJ-1
      as an antioxidant and/or a molecular chaperone. Elucidating the role of DJ-1 will
      lead to a better understanding of the pathogenesis of DJ-1-related and common
      forms of Parkinson's disease.

PMID- 14598066
TI  - The diagnostic importance of the isolated supranuclear downward gaze
      ophthalmoplegia in progressive supranuclear palsy.

PMID- 14598067
TI  - Dopaminergic degeneration and perfusional impairment in Lewy body dementia and
      Alzheimer's disease.
AB  - The clinical differentiation of Lewy body dementia (LBD) from Alzheimer's disease
      (AD) may be difficult. The aim of the present study was to assess the dopamine
      transporter function and the perfusional pattern in LBD and AD in vivo. Twenty
      patients with probable LBD and 24 with probable AD underwent on 2 separate days a
      brain perfusional SPECT with 99mTc-ECD and a SPECT with (123)I-FP-CIT, a ligand
      of dopamine transporter. In LBD a significantly ( p<0.0005) lower ratio of
      specific (bilateral caudate nucleus, putamen) to non-specific (occipital cortex)
      (123)I-FP-CIT binding than in AD was reported. Perfusional data (SPM analysis)
      showed a significant ( p<0.001) decrease of temporo-parietal blood flow in AD
      versus LBD, whereas in LBD a significant ( p<0.001) occipital hypoperfusion with
      respect to AD was reported. Our findings confirm that dopaminergic nigrostriatal
      function is impaired in LBD. The selective occipital hypoperfusion in LBD needs
      to be further investigated.

PMID- 14598068
TI  - Presence of beta-arrestin in cellular inclusions in metamphetamine-treated PC12
      cells.
AB  - Cellular inclusions containing ubiquitin and alpha-synuclein were observed in
      PC12 cells treated with metamphetamine (MA). To study the possible involvement of
      beta-arrestin in inclusion formation, we treated PC12 cells with MA for different
      times and analyzed the ubiquitin proteosome pathway (UPP). We found that beta
      arrestin is ubiquitinated in the MA-treated PC12 cell line. The involvement of
      beta-arrestin in UPP was further supported by electron microscopy and by confocal
      microscopy, which documented the presence of beta-arrestin in these Lewy body
      like inclusions. Our experiments reveal an interesting and previously
      unappreciated connection between beta-arrestin and ubiquitination and suggest
      that beta-arrestin could be involved in the development of the inclusion bodies.

PMID- 14598069
TI  - Dementia, ataxia, extrapyramidal features, and epilepsy: phenotype spectrum in
      two Italian families with spinocerebellar ataxia type 17.
AB  - We observed two families with a dominantly inherited complex neurological
      syndrome with onset in adulthood. Family F included 9 affected in four
      generations. One patient showed prominent anticipation of onset age. Onset was
      with cerebellar signs followed by dementia, psychiatric symptoms, seizures, and
      extrapyramidal features. Family M included 14 affected individuals in five
      generations. Presenting symptoms were either psychiatric and cognitive impairment
      or a cerebellar syndrome. Extrapyramidal features, dysphagia, incontinence,
      seizures, and myoclonus may occur. In both families magnetic resonance imaging
      showed marked atrophy of the brain and cerebellum. Molecular analyses
      demonstrated an expanded CAG/CAA repeat in the in the TATA box-binding protein
      (TBP) gene (SCA17).

PMID- 14598070
TI  - Frequency of familial aggregation in primary adult-onset cranial cervical
      dystonia.
AB  - Family history of definite/probable dystonia was studied in 36 probands with
      primary adult-onset cranial/cervical dystonia. Of the 157 relatives who were
      examined, 8 from 7 families and 11 from 10 families were diagnosed as having
      definite or probable dystonia, respectively. The frequency of familial occurrence
      of definite dystonia was 19.4%, 33% when considering both definite and probable
      dystonia. There was a tendency for relatives affected by either definite or
      probable dystonia to have the same type of dystonia as the index patient. Similar
      segregation ratios were found for parents, siblings, and children with either
      definite or probable dystonia. These observations raise the possibility that
      probable dystonia represents formes frustes/mild phenotypes of dystonia rather
      than another movement disorder.

PMID- 14598071
TI  - Bedtime cabergoline in Parkinson's disease patients with excessive daytime
      sleepiness induced by dopamine agonists.
AB  - Excessive daytime somnolence is a common adverse effect of dopamine-agonist
      treatment of Parkinson's disease (PD). Many factors, such as age and sleep
      disturbances, could be involved in the pathogenesis of this phenomenon. However,
      pharmacokinetic factors have never been considered. In this open, prospective,
      pilot study, nine consecutive non-demented PD patients in early disease stages on
      monotherapy treatment with dopamine agonists and with no significant sleep
      problems, were enrolled. They were selected based on the presence of excessive
      daytime sleepiness induced by the dopaminergic treatment. A fast switch-over from
      the dopamine agonist currently used to a single equivalent dose of cabergoline, a
      long-acting dopamine agonist, administered at bedtime was performed. All patients
      were evaluated by means of UPDRS and Epworth Sleepiness Scale (ESS). A
      significant 70% reduction of daytime sleepiness was observed during the 3-month
      study compared with baseline. Data from this study suggest that both
      pharmacodynamic and pharmacokinetic mechanisms are involved in the
      pathophysiology of dopamine agonist-induced sleepiness.

PMID- 14598072
TI  - Decreased plasma and cerebrospinal fluid content of neuroactive steroids in
      Parkinson's disease.
AB  - The levels of the neuroactive steroids allopregnanolone (THP) and 5alpha
      dihydroprogesterone (DHP) were quantified in the plasma of 11 (group 1) and in
      the liquor of 12 (group 2) Parkinson's disease (PD) patients using a gas
      chromatographic/mass-spectrometric method. When compared with controls, both
      groups showed a significant decrease in DHP and THP concentrations. These
      decreases could be a useful marker of PD. Moreover, in view of the importance of
      GABA-ergic transmission to substantia nigra (SN) neurons and GABA-ergic
      modulation exerted by the two neuroactive steroids, our data indicate a global
      dysregulation of the SN GABA-ergic system in PD patients. Moreover, a lack of
      neuroprotective factors (i. e., GDNF, BDNF), promoted by DHP, may contribute to
      dopaminergic cell death.

PMID- 14598073
TI  - Continuous apomorphine infusion and neuropsychiatric disorders: a controlled
      study in patients with advanced Parkinson's disease.
AB  - The aim of this study was to assess whether patients with Parkinson's disease
      (PD) develop cognitive and psychiatric complications more frequently during
      prolonged therapy with continuous apomorphine infusion compared with standard
      oral treatment. Thirty consecutive PD patients with severe motor fluctuations
      were included in the study. Twelve patients accepted the treatment with
      subcutaneous continuous apomorphine infusion, while the remaining 18 preferred to
      continue with oral dopaminergic therapy. The two groups were evaluated with
      neuropsychological, psychiatric, and motor tests at baseline and after 1 year.
      The off daily duration and the levodopa dosage were significantly reduced in
      infused patients. The neuropsychiatric assessment did not change in both groups
      compared with baseline, except for a significant improvement of mood in the
      apomorphine group.

PMID- 14598074
TI  - Natural history and clinical features of progressive supranuclear palsy: a
      clinical study.
AB  - Progressive supranuclear palsy (PSP or Steele-Richardson-Olszewski syndrome) is
      one of the most-common types of atypical parkinsonism. To characterize the
      natural history and the clinical features of PSP, we reviewed the records of 25
      patients followed in our clinic since 1991, with a clinical diagnosis of PSP
      according to NINDS and Golbe criteria. Progressive onset of early bilateral
      bradykinesia and postural instability with falls during the 5th decade strongly
      support the diagnosis of PSP in our patients. Pseudobulbar symptoms are very
      common at onset and during the course of the illness.

PMID- 14598075
TI  - Excessive daytime somnolence in Parkinson's disease. Follow-up after 1 year of
      treatment.
AB  - Excessive daytime somnolence (EDS) and quality of sleep were studied in 25
      parkinsonian patients at baseline, when they had not yet received any
      antiparkinsonian medication, and after 1 year of treatment with dopaminergic
      drugs. EDS was measured by the Epworth Sleepiness Scale (ESS) and sleep quality
      by the Pittsburgh Sleep Quality Index (PSQI). At baseline, the ESS score was not
      different from that of age-matched healthy controls. The mean ESS score increased
      significantly after 1 year of follow-up, being more than 10 in 12 patients. The
      mean PSQI also increased significantly after 1 year of treatment, but there were
      no differences in the number of "bad sleepers" at baseline and at follow-up. In
      conclusion, EDS seems to emerge during the course of the illness, at least in a
      proportion of PD patients, and could represent another clinical correlate of the
      interaction between the ongoing neurodegenerative process and the side effects of
      drugs.

PMID- 14598076
TI  - Neuroprotective effects mediated by dopamine receptor agonists against malonate
      induced lesion in the rat striatum.
AB  - In rats, intrastriatal injection of malonate, a reversible inhibitor of the
      mitochondrial enzyme succinate dehydrogenase, induces a lesion similar to that
      observed following focal ischemia or in Huntington's disease. In this study we
      used the malonate model to explore the neuroprotective potential of dopamine
      agonists. Rats were injected intraperitoneally with increasing concentrations of
      D1, D2, or mixed D1/D2 dopamine agonists prior to intrastriatal injection of
      malonate. Administration of increasing doses of the D2-specific agonist
      quinpirole resulted in increased protection against malonate toxicity.
      Conversely, the D1-specific agonist SKF-38393, as well as the mixed D1/D2 agonist
      apomorphine, conferred higher neuroprotection at lower than at higher drug
      concentrations. Our data suggest that malonate- induced striatal toxicity can be
      attenuated by systemic administration of dopamine agonists, with D1 and D2
      agonists showing different profiles of efficacy.

PMID- 14598078
TI  - Deficit of short-term memory in newly diagnosed untreated parkinsonian patients:
      reversal after L-dopa therapy.
AB  - We assessed the effect of pathology and L-dopa therapy on attention, working
      memory, and executive functions, in newly diagnosed Parkinson's disease patients.
      Twenty-one consecutive outpatients who met the criteria for de novo Parkinson's
      disease, and were naive for L-dopa therapy, were observed for the first time. All
      patients underwent clinical and neuropsychological evaluations (cognitive
      decline, memory, executive control). Each patient was reevaluated on standard L
      dopa therapy. Serial Position Curves showed an increased primacy effect (5.18+/
      2.07) and a decreased recency effect (13.35+/-5.51). These findings normalized
      after L-dopa therapy (3.50+/-1.72 and 16.20+/-3.09 respectively). The effect of L
      dopa on working memory is discussed.

PMID- 14598077
TI  - Amphetamines induce ubiquitin-positive inclusions within striatal cells.
AB  - The present study explores whether effects induced by amphetamine derivatives on
      striatal GABA cells might be connected with effects on dopamine (DA) metabolism.
      Methamphetamine (METH) and 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy")
      were administered to C57Black mice following a dosage regimen in which various
      doses of both drugs were injected i.p. at 2-h intervals. Neuronal inclusions
      produced under these experimental conditions were examined under electron
      microscopy. Drugs reducing DA availability prevented inclusion formation;
      conversely we observed that increasing DA synthesis or impairing physiological DA
      degradation enhanced the number of inclusions. The present study indicates that
      the presence of extracellular striatal DA is essential for the production of
      subcellular alterations induced by amphetamine derivatives. This is in line with
      a recent hypothesis connecting striatal DA release with degeneration of striatal
      GABA neurons.

PMID- 14598079
TI  - Progressive supranuclear palsy: analysis of six cases.
AB  - We analyzed six cases of progressive supranuclear palsy (PSP) from 1 January 1998
      to 31 June 2002. All patients underwent a complete range of laboratory tests,
      head computed tomographic (CT) scan or magnetic resonance imaging (MRI); three
      were evaluated by formal neuropsychological examination. All were taking L-dopa
      or dopamine agonists. At the onset of PSP the initial diagnosis was almost always
      Parkinson's disease. The head CT scan or MRI findings were non-specific, while
      neuropsychological testing disclosed cognitive impairment, with predominant
      subcortical-frontal involvement. We emphasize the still obvious current
      difficulty in diagnosing PSP at an early stage in clinical practice. Therefore it
      is essential to formulate better clinical diagnostic criteria, to permit correct
      management of the disease.

PMID- 14598080
TI  - Neuroacanthocytosis: clinical, radiological, and neurophysiological findings in
      an Italian family.
AB  - We have studied three members of a family (mother and two siblings) where the
      mother and father were first cousins and who presented a history of progressive
      mental deterioration, hyperkinetic extrapyramidal disorders, and epileptic
      seizures. They underwent the following examinations: cupremia, cupruria, and
      level of ceruloplasmin, genetic analysis for SCA1, 2, 3, 6, dentato-rubric
      pallido-luysian atrophy, and Huntington's disease, electromyography (EMG),
      electroencephalography (EEG), brain magnetic resonance imaging (MRI), and
      investigation of acanthocytes with scanning electron microscopy. Genetic analysis
      was negative in all patients and acanthocytes were positive. EMG showed an axonal
      neuropathy in one sibling, EEG showed epileptiform activity in the two siblings,
      and MRI showed cortical atrophy in all subjects. This family shows the great
      variability of neuroacanthocytosis and a dominant autosomal transmission, as
      described only once previously in the literature.

PMID- 14598081
TI  - Psychometric properties of the Unified Parkinson's Disease Rating Scale and of
      the Short Parkinson's Evaluation Scale.
AB  - The internal consistency (Cronbach's alpha and item-total correlation) and
      construct validity (factor analysis, intercorrelations, and relationship with
      Hoehn and Yahr staging and Schwab and England's ADL scale) of the sections "motor
      examination" and "activities of daily living" of the Unified Parkinson's Disease
      Rating Scale (UPDRS) and of the Short Parkinson's Evaluation Scale (SPES) were
      analyzed in 59 subjects with Parkinson's disease (PD) with various degrees of
      disability. Our results indicate that the SPES is easier and quicker than UPDRS
      and that it maintains many psychometric properties similar to those of the UPDRS,
      but with the reduction of a number of items and ordinal levels of each item
      studied here (producing more homogenous sections than the original versions). The
      tremor items would be better represented as a separate section in both scales.

PMID- 14598082
TI  - Levodopa pharmacokinetics and dyskinesias: are there sex-related differences?
AB  - We examined the potential sex-related differences in levodopa pharmacokinetics
      and their relation with the presence of dyskinesias in a group of 115 patients
      (67 men, 49 women) with Parkinson's disease. The patients were given a standard
      oral dose of levodopa plus benserazide (100/25 mg). The area under the levodopa
      plasma concentration time curve, corrected for the levodopa test dose (in mg/kg
      body weight), (AUC(w)) was significantly higher in women than in men, with a
      reduced oral clearance. No difference in the proportion of men and women
      experiencing dyskinesias was observed.

PMID- 14598083
TI  - Six years' experience in deep brain stimulation in Parkinson's disease:
      advantages and limitations of use of neurophysiological intraoperative
      microreading.

PMID- 14598084
TI  - Sleep attacks in Parkinson's disease: a clinical and polysomnographic study.
AB  - The objective of the study was to evaluate daytime sleepiness, (the features of
      episodes of sudden sleep onset), i. e., so-called sleep attacks (SAs), in three
      male Parkinson's disease (PD) patients (mean age 66 years) on chronic therapy
      with ropirinole or pramipexole. A structured clinical interview, the Epworth
      Sleepiness Scale, and continuous 24-h ambulatory polysomnography were used to
      assess the features of SAs occurring in the patients in their normal home
      environments. The polysomnographic patterns characterizing SAs (sleep occurring
      against a background of wakefulness, and not preceded by a feeling of sleepiness
      or by other heralding symptoms) were analyzed. The results showed that SAs can be
      clearly documented through polysomnographic monitoring and really, but rarely,
      occur in PD. SAs seem to represent the extreme of the continuum of daytime
      sleepiness observed in PD patients.

PMID- 14598085
TI  - The use of entacapone in patients with advanced Parkinson's disease: 2 years'
      experience.
AB  - Since January 2000 we have administered entacapone (200 mg) to 75 patients with
      severe Parkinson's disease in combination with their routine levodopa dose. At
      baseline the mean UPDRS (item III) score was 38+/-6. After 3 months of entacapone
      therapy the patients presented a significant improvement of motor fluctuations;
      the mean UPDRS score (item III) was 20+/-4. This improvement was also
      statistically significant after 2 years of entacapone therapy.

PMID- 14598086
TI  - Cerebrospinal fluid biochemical markers in early detection and in differential
      diagnosis of dementia disorders in routine clinical practice.
AB  - Measurement of total tau and amyloid beta1-42 (Ab42) in cerebrospinal fluid (CSF)
      improves diagnostic accuracy of Alzheimer's disease (AD). We examined a
      consecutive patient sample referred to our center for diagnostic assessment of
      cognitive decline. CSF tau and Abeta42 were assayed each week as routine
      neurochemical analyses. There were 119 patients investigated. These included 61
      with probable AD (35 mild AD, 26 severe AD), 24 with mild cognitive impairment
      (MCI), 14 with vascular dementia, 11 with Lewy body dementia, and 9 with fronto
      temporal dementia. Mild AD showed significantly lower CSF Abeta42 levels and
      significantly higher CSF tau levels than the other diagnostic groups; 79% of MCI
      patients had pathological values for both biomarkers. We confirm that these
      biomarkers have a role in the clinical work-up of patients with cognitive
      deficits.

PMID- 14598087
TI  - A paradoxical acute effect of levodopa in de novo parkinsonian patients:
      worsening of some bradykinetic components.
AB  - Reports of alterations of reaction times (RTs) in Parkinson's disease are often
      discordant, particularly when the aim of the research is investigation of the
      relationship between levodopa (LD) administration and RTs. Slowing of simple RT
      in a group of de novo parkinsonian patients 30-90 min after administration of LD
      (Madopar 250) was recently reported. This temporary phenomenon was attributed to
      a sedative effect of LD. Our present study aimed to repeat these investigations
      using Multiple Delayed Reaction Verbochronometry (MDRV). We conclude that such a
      slowing is not a temporary phenomenon but may represent the increased time
      necessary for the subject to adequately perform the reaction tasks.

PMID- 14598088
TI  - Caregiving and Parkinson's disease.
AB  - Relatively little has been published in the international literature concerning
      the caregiving-related problems associated with Parkinson's disease. We therefore
      undertook two exploratory studies that have allowed us to identify the needs and
      specific problems perceived by such caregivers in both qualitative and
      quantitative terms.

PMID- 14598089
TI  - Hedonistic homeostatic dysregulation in Parkinson's disease: a short screening
      questionnaire.

PMID- 14598090
TI  - Nocturnal anomalous movement reduction and sleep microstructure analysis in
      parkinsonian patients during 1-night transdermal apomorphine treatment.
AB  - This study analyzed the macrostructure and microstructure of sleep in 12
      parkinsonian patients under basal conditions (T0) and during 1-night treatment
      (T1) with a new formulation of apomorphine. This new formulation consisted in a
      microemulsion of apomorphine administered by the transdermal route, able to
      provide a constant release of the drug over several hours (APO-TD). Sleep
      analysis at T1 compared with T0 revealed a 16% increment of total sleep time, a
      12% increment of sleep efficiency, a 16% increment of stage 3 and 4 non-REM
      sleep, a 15% reduction of periodic limb movements index, a 22% reduction of
      arousal index, and a 23% reduction of cycling alternating patterns/non-REM. We
      conclude that APO-TD may be able to reduce nocturnal anomalous movements,
      akinesia, and rigidity in Parkinson's disease, and may reduce the disturbed sleep
      typical of Parkinson's disease.

PMID- 14598091
TI  - Health-related quality of life and sleep disorders in Parkinson's disease.
AB  - Parkinson's disease (PD) is a chronic, progressive, disabling movement disorder
      with a clear impact on Health-Related Quality of Life (HRQoL). We investigated
      the correlations between HRQoL and sleep disorders measured with the Parkinson's
      disease Sleep Scale (PDSS) and the motor and non-motor aspects of the disease. A
      correlation was found between HRQoL and the scores from PDSS, motor and
      depression scales. We conclude that more attention should be paid to the non
      motor aspects of PD to attempt to improve HRQoL.

PMID- 14598092
TI  - Progressive dysarthria: definition and clinical follow-up.
AB  - Progressive dysarthria is a common sign of several degenerative disorders of the
      central nervous system; it may also be a distinct nosographic entity. We
      identified nine patients in which progressive dysarthria remained the sole
      neurological sign for at least 2 years after onset. At least a year after
      hospital admission, the following diagnoses were made: two cases of corticobasal
      degeneration, one of frontotemporal dementia, one of primary progressive aphasia,
      one of motor neuron disease (MND)-dementia, one of ALS, and one of ALS-aphasia.
      In the remaining two patients progressive dysarthria remained the only
      neurological sign at latest examination. We conclude that in most cases
      progressive dysarthria is the presenting sign of an established neurodegenerative
      disease (generally degenerative dementia or motor neuron disease), although the
      possibility that progressive dysarthria is a distinct entity cannot be excluded.
      To clarify this issue, studies (probably multicenter) on more patients with
      longer clinical follow-up and pathological confirmation are required.

PMID- 14598093
TI  - Distal-proximal differences in limb apraxia in corticobasal degeneration but not
      progressive supranuclear palsy.
AB  - Limb apraxia is an important diagnostic sign of cortico-basal degeneration (CBD),
      although it is also found in progressive supranuclear palsy (PSP). We
      investigated whether the severity of apraxia differed between proximal and distal
      arm movements in the two diseases, as suggested by their differing patterns of
      motor impairment. We studied 24 CBD patients, 25 PSP patients, and 19 healthy
      controls using a battery of cognitive tests and an ideomotor apraxia test that
      examined imitation of hand and of whole arm gestures separately. CBD and PSP
      patients did not differ in general characteristics or disability and were
      similarly impaired in cognitive performance. Within-group differences between
      distal and proximal gesture scores were significant only for CBD patients (
      p=0.007), in whom distal movements were more compromised. This finding suggests
      the presence of limb kinetic apraxia in CBD, perhaps in association with
      ideomotor apraxia.

PMID- 14598094
TI  - Italian Huntington disease patients--data and tissue bank.
AB  - We have collected clinical and genetic data on Huntington disease (HD) patients
      and their families over the last 5 years at the Unit of Neurogenetics, IRCCS
      Neuromed of Pozzilli (IS), Italy. Data on 854 mutation carriers are included in
      the data bank, together with a large number of DNA samples, blood, and other
      tissues. In particular, lymphoblastoid cell lines from 100 patients, including
      subjects carrying very rare genetic conditions (CAG mutation homozygosity,
      juvenile and infantile onset, pre-mutations) have been established. For all these
      initiatives ethical approval from the bioethics committee was obtained. We wish
      to extend this initiative to all families, investigators, and institutions within
      and, possibly outside, the Italian border in an attempt to enlarge the bank and
      to institute a HD Research Roster.

PMID- 14598096
TI  - Acute akinesia or akinetic crisis in Parkinson's disease.
AB  - In 22 patients with idiopathic Parkinson's disease we observed a sudden worsening
      of motor symptoms and severe akinesia during hospitalization because of
      infectious diseases, bone fractures, surgery for gastrointestinal tract diseases,
      and iatrogenic causes. Of these patients, 12 recovered completely, 6 had a
      partial recovery, and 4 died. Treatments included subcutaneous
      apomorphine/lisuride infusion and dantreolene (with a creatine phosphokinase
      level higher than 200 IU). In all patients a definite refractoriness to therapy
      was shown with a transient lack of response to apomorphine.

PMID- 14598095
TI  - Optimizing levodopa pharmacokinetics in Parkinson's disease: the role of COMT
      inhibitor.

PMID- 14598097
TI  - Current status of left ventricular assist devices: the role in bridge to heart
      transplantation and future perspectives.
AB  - Increasing numbers of patients with end-stage heart failure are awaiting heart
      transplantation worldwide. Left ventricular assist systems have been applied to
      these patients with increasing frequency and support duration. This situation
      calls for more reliably applied long-term support devices and is also stimulating
      the investigation of destination therapy or bridge to recovery use of the device.
      This is particularly relevant in countries where organ shortages are crucial.
      However, reports in this area are still limited, and there exist several problems
      to be solved before wider application of these strategies is possible in clinical
      practice. We review currently available devices with special reference to their
      respective roles and limitations quoting our own experiences over the past
      several years, and discuss future perspectives of ventricular assist devices.

PMID- 14598098
TI  - Design of a miniature implantable left ventricular assist device using CAD/CAM
      technology.
AB  - In this study, we developed a new miniature motor-driven pulsatile left
      ventricular assist device (LVAD) for implantation into a Japanese patient of
      average build by means of computer-aided design and manufacturing (CAD/CAM)
      technology. A specially designed miniature ball-screw and a high-performance
      brushless DC motor were used in an artificial heart actuator to allow
      miniaturization. A blood pump chamber (stroke volume 55 ml) and an inflow and
      outflow port were designed by computational fluid dynamics (CFD) analysis. The
      geometry of the blood pump was evaluated using the value of index of pump
      geometry (IPG) = (Reynolds shear stress) x (occupied volume) as a quantitative
      index for optimization. The calculated value of IPG varied from 20.6 Nm to 49.1
      Nm, depending on small variations in pump geometry. We determined the optimum
      pump geometry based on the results of quantitative evaluation using IPG and
      qualitative evaluation using the flow velocity distribution with blood flow
      tracking. The geometry of the blood pump that gave lower shear stress had more
      optimum spiral flow around the diaphragm-housing (D-H) junction. The volume and
      weight of the new LVAD, made of epoxy resin, is 309 ml and 378 g, but further
      miniaturization will be possible by improving the geometry of both the blood pump
      and the back casing. Our results show that our new design method for an
      implantable LVAD using CAD/CAM promises to improve blood compatibility with
      greater miniaturization.

PMID- 14598099
TI  - A novel diaphragm-to-housing junction adhesive method: alumina ball milling.
AB  - An alumina ball milling method was applied to enhance the adhesiveness and
      smoothness of the diaphragm-to-housing (D-H) junction. The impact produced by the
      three rotating alumina balls along the meshed junction made the surface of the
      junction uniform and smooth. The quality of the D-H junction was evaluated by
      various methods, such as inspection using an optical microscope and a scanning
      electron microscope, smoothness examination by an atomic force microscope, and
      measurement of the tensile strength. All the evaluations revealed marked
      improvements, and the platelet adhesion test revealed that the alumina ball
      milling method plays an important role in the blood compatibility enhancement of
      the D-H junction.

PMID- 14598100
TI  - Vascular prosthetic implantation is associated with prolonged inflammation
      following aortic aneurysm surgery.
AB  - The purpose of this study was to semiquantify the magnitude of surgical stress in
      patients undergoing aortic surgery by measuring inflammatory responses
      perioperatively, focusing on cytokine secretion. Serum concentrations of
      interleukin (IL) 1alpha, IL-6, IL-8, and tumor necrotizing factor (TNF) Alpha
      were measured in patients undergoing abdominal or thoracic aortic aneurysmectomy
      preoperatively and periodically thereafter for 2 weeks. Urinary trypsin inhibitor
      (UTI/Cr) and C-reactive protein (CRP) concentration and the systemic inflammatory
      response syndrome (SIRS) score also were determined. Indices of inflammation and
      cytokine concentrations peaked at 1-3 days after surgery and decreased
      thereafter; however, IL-8 increased again after day 7. Concentrations of IL-8,
      UTI/Cr, and CRP and the SIRS score were still higher 14 days after surgery than
      preoperatively. The maximum concentrations of IL-6 and IL-8 were higher after
      thoracic than abdominal aortic repair; however, the maximum values of cytokines
      were not correlated with operative factors in all patients. A patient suffering
      from graft infection showed an increase in cytokine concentrations on day 7. The
      inflammatory response does not return to preoperative values within 2 weeks of
      surgery in patients undergoing thoracic or abdominal aortic aneurysm repair. The
      prolonged secretion of IL-8 suggests a host reaction to the synthetic prosthesis.
      A large increase in inflammatory cytokines on day 7 may indicate infection of the
      vascular graft.

PMID- 14598101
TI  - Pannus formation in aortic valve prostheses in the late postoperative period.
AB  - We present three patients who underwent repeat aortic valve replacement for
      prosthetic valve dysfunction caused by tissue ingrowth in the late postoperative
      period. These patients (three women aged 48-51 years, mean 49.3 +/- 1.53 years)
      underwent operations for restriction of prosthetic valve leaflet movement by
      pannus in the left ventricular outflow tract. The interval from the previous
      operation ranged from 8.0 to 9.6 years (mean 9.6 +/- 2.0 years). The symptoms of
      the patients were New York Heart Association functional class I, II, and IV in
      one patient each. Diagnosis was made by cinefluoroscopy in two patients and
      aortography in one patient. The operative procedures consisted of aortic valve
      replacement ( n = 1) and aortic valve replacement with mitral valve replacement (
      n = 2). Pannus was found at the left ventricular aspect of the prosthetic valve
      in all patients. In two patients, the pannus directly restricted movement of the
      leaflet and also severely narrowed the inflow orifice of the prosthetic valve. In
      the other patient, the pannus had grown at a distance of 7 mm from the valve and
      narrowed the left ventricular outflow tract circularly. The postoperative course
      was uneventful and all three patients were discharged in a good condition. One
      patient died of pneumonia 8 months after surgery and the other two patients have
      remained well and have been followed up for one and a half years. In conclusion,
      there may be a discrepancy between the clinical symptoms and the grade of
      subvalvular stenosis caused by pannus. Therefore, it is essential for
      satisfactory operative results that early diagnosis be made by various means.

PMID- 14598102
TI  - The isolated normothermic hemoperfused porcine forelimb as a test system for
      transdermal absorption studies.
AB  - For transdermal absorption studies, a porcine skin model that maintains the
      characteristics of the skin as close to physiological conditions as possible
      should be established because of the close similarity of porcine and human skin.
      Perfusion flow, glucose concentration, and oxygen supply were varied and organ
      resistance and lactate concentration were measured as parameters for organ
      performance. Transdermal absorption studies were performed using nitroglycerin or
      estradiol as test solutes. By the use of a standardized perfusion apparatus,
      limbs were perfused with a normothermic blood/electrolyte mix over a 6-h period.
      Organ resistance and lactate concentration were lower in limbs perfused with high
      flow as compared to perfusion with low flow. However, high perfusion flow caused
      an initial increase of hemolysis in the venous perfusate resulting in a higher
      concentration of free hemoglobin compared to low perfusion flow conditions.
      Glucose level in the perfusate was maintained within the porcine physiological
      range. By applying optimized conditions, the transdermal absorption of
      nitroglycerin or estradiol released from transdermal therapeutic systems was
      investigated. A time-dependent accumulation of the substances in the perfusion
      medium was observed, indicating the continuous uptake via the skin. After 6 h
      (nitroglycerin) or 5 h (estradiol) of perfusion, test substances accumulated to
      concentrations comparable to those described in humans. In conclusion the
      perfused porcine limb may serve as a reliable test system for transdermal
      absorption studies. The model is suited to the replacement of animal testing and
      has a higher predictive potential because of the similarities of porcine and
      human skin.

PMID- 14598103
TI  - Measurements of the mechanical properties of contracted collagen gels populated
      with rat fibroblasts or cardiomyocytes.
AB  - In this paper the mechanical properties of contracted collagen gels populated
      with rat fibroblasts or cardiomyocytes were investigated by means of uniaxial
      tensile testing. Rat type I collagen-Dulbecco's modified Eagle's medium (DMEM)
      gels (each 2 ml in volume, 0.5 mg/ml collagen concentration) populated with
      different numbers of rat fibroblasts or cardiomyocytes were made in 31 x 17-mm
      wells cut in silicone rubber located in a 100-mm diameter plastic dish.
      Identically treated gels were incubated for 4 days floating in DMEM and then were
      subjected to uniaxial tensile testing. Rapid contraction occurred within the
      first 3 days for both the fibroblast and cardiomyocyte gels, but the
      cardiomyocyte gels consistently contracted to smaller sizes than the fibroblast
      gels for each number of cells used. The tension-strain curve of the contracted
      collagen gels demonstrated exponential behavior in the low stress region,
      followed by a linear section, and finally a maximum tension point, giving the
      ultimate strength of the gel tested. The cardiomyocyte gels had higher tension
      strain curves than the fibroblast gels for each number of cells used. The tension
      relaxation and cyclic creep phenomena were observed in both kinds of gels, and
      these phenomena coincide with prior observations in collagen gels contracted by
      human fibroblasts. This experiment shows that type I collagen gels can be
      significantly contracted by rat fibroblasts or cardiomyocytes so as to achieve a
      certain mechanical strength. The contracted collagen structures made in these
      experiments have potential for developing tissue-engineered structures for
      cardiac muscle studies.

PMID- 14598104
TI  - Nondestructive evaluation of blood flow in a dialyzer using X-ray computed
      tomography.
AB  - It is very important to observe the concentrations and flow patterns of blood
      through a dialyzer to evaluate its function and to obtain the most appropriate
      design. We established a visualization method for the blood flow pattern in a
      dialyzer using X-ray computed tomography, and investigated the so-called internal
      filtration phenomenon. The results obtained were as follows: (1). The influence
      of 5% BaSO(4), which was added to the blood as a contrast medium, on the
      filtration rate of the dialyzer was minimal. (2). The relationship between the
      concentration of BaSO(4) and the Hounsfield unit value was expressed by linear
      regression. (3). Hounsfield unit values increased massively just after blood
      entered the dialyzer and peak values increased with dialysate perfusion under the
      following conditions: the dialyzer (BS-1.6UL, polysulfone hollow fibers) was
      used, and bovine blood with 5% BaSO(4) added was used at a blood flow rate of 200
      ml/min. The dialysate flow rate was 500 ml/min and the slice thickness of X-ray
      computed tomography was 1-10 mm. (4). It was observed that blood flowed slightly
      faster in the center than the peripheral portion of the dialyzer, when the flow
      pattern was followed after pulse injection of blood containing 20% BaSO(4) into
      the dialyzer. It was concluded that this method could possibly be utilized not
      only qualitatively but also quantitatively for observation of the real state of
      blood flow and in designing dialyzers.

PMID- 14598105
TI  - Selection of hemoperfusion therapy for patients with septic shock on the basis of
      the primary disease.
AB  - The objective of this study was to analyze retrospectively the efficacy of
      polymyxin-B immobilized fiber (PMX-F) alone and in combination with continuous
      venovenous hemofiltration (CHF) on the prognosis of critically ill patients with
      sepsis using a retrospective chart review in a university hospital in Japan. A
      cohort of 246 patients meeting the criteria of sepsis, septic shock, or both,
      according to the American College of Chest Physicians/Society of Critical Care
      Medicine (ACCP/ACCM) Consensus Conference, were examined in this study. From
      these patients, 48 were selected who were found to have definitive causative
      bacteria and whose primary diseases were clearly identified. According to the
      charts, two major primary diseases were identified: one related to cardiovascular
      disease and the other to gastrointestinal disease. Other diseases were excluded
      from this study because of the small numbers of patients in categories such as
      malignant, hematological, genitourinary, and other diseases. Furthermore,
      patients who had levels of serum creatinine above 2.0 mg/dl were excluded. The
      prevalence of diabetes mellitus (up to 63%) was very high in both groups. There
      were no significant differences between the two groups in age or the Apache II
      scores at the start of hemoperfusion treatment; however, the gender ratio varied:
      72% of the cardiovascular group were male, compared to 46% of the
      gastrointestinal group. The causative bacteria were markedly different between
      the two groups. For half of the gastrointestinal group the causative bacterium
      was Escherichia coli, while for half of the cardiovascular group the causative
      bacterium was Pseudomonas aeruginosa. The survival rate differed significantly
      between the two groups. The patients in the cardiovascular group survived longer
      than those in the gastrointestinal group. Moreover, for the patients with
      cardiovascular disease, there was no significant difference in the survival rate
      between treatment with PMX-F alone and with PMX-F and CHF in combination. In
      contrast, for the patients with gastrointestinal disease, there was a significant
      difference between treatment with PMX-F alone and with PMX-F and CHF in
      combination. When a patient with sepsis or septic shock is treated with
      hemoperfusion, the decision as to whether PMX-F should be given alone or in
      combination with CHF might be determined on the basis of the primary disease of
      the patient.

PMID- 14598106
TI  - Development of a new extracorporeal whole-liver perfusion system.
AB  - We have developed a new extracorporeal whole-liver accommodation device in which
      a whole swine liver is placed in a physiological state by modeling the
      intraabdominal arrangement in the pig body, with the liver supported by a special
      inferior vena cava tube. Furthermore, we employed a diaphragm-type artificial
      heart in our system to produce pulsatile blood flow through the hepatic artery,
      which is considered to be indispensable to dilate peripheral vessels and supply
      oxygenated whole blood to the peripheral liver tissue. Beneficial effects were
      demonstrated in visual findings and bile juice secretion. The color of the liver
      surface in our system remained bright red, indicating that the liver vessels were
      well drained and free from congestion, and bile juice secretion was maintained at
      more than 10 ml/h throughout the perfusion period. Our system exhibited excellent
      ammonia removal and urea nitrogen synthesis, and serum aspartate aminotransferase
      levels showed no increase, indicating the absence of hepatocyte destruction.
      Histological findings showed that the liver could expand appropriately and was
      free from compression caused by its own weight. In conclusion, our original liver
      accommodation device enabled appropriate expansion of the whole liver and
      supplied adequate oxygenated blood to peripheral areas by means of a pulsatile
      pump.

PMID- 14598107
TI  - A case in which biventricular assist device support was required after aortic
      valve replacement with a bioprosthetic valve.
AB  - We report the case of a 45-year-old man with severe aortic regurgitation. The
      patient underwent aortic valve replacement with a bioprosthetic valve, but was
      unable to be weaned from cardiopulmonary bypass (CPB). Intraoperative coronary
      angiography revealed stenosis of the right coronary orifice, so an intra-aortic
      balloon pump was inserted and coronary artery bypass grafting to the right
      coronary artery was conducted; however, weaning from CPB again failed. Left
      ventricular assist using a Gyro centrifugal pump was performed between the left
      atrium and left femoral artery, along with right ventricular assist using a
      Nikkiso centrifugal pump between the right atrium and pulmonary artery. Flow
      rates averaged from 2.0 to 2.8 l/min for the left-side ventricular assist device
      (VAD) and 2.1-3.8 l/min for the right-side VAD. The bypass rate reached
      approximately 70% at maximum. No thromboembolic events were documented during VAD
      support. The patient underwent explantation of VADs on postoperative day 4. No
      thrombus was identified on the bioprosthetic aortic valve by transesophageal
      echocardiography. The left-side pump displayed no thrombus, while the right-side
      pump had a small thrombus at the shaft. The patient was discharged from the
      hospital and was alive as of 2 year postoperatively. To the best of our
      knowledge, no clinical study has yet compared the antithrombotic properties of
      two centrifugal pumps in one patient where mechanical support was performed for
      the same duration and flow rate.

PMID- 14598108
TI  - Hydrodynamically stable adhesion of endothelial cells onto a polypropylene hollow
      fiber membrane by modification with adhesive protein.
AB  - The effect on the adhesion of endothelial cells of immobilization of adhesion
      proteins onto a microporous polypropylene hollow fiber membrane for a
      conventional artificial lung was investigated with the aim of constructing a
      hybrid artificial lung bearing endothelial cells on the modified membrane. The
      membrane was modified by adsorption or covalent bonding of adhesion proteins of
      fibronectin, gelatin, or Pronectin. The density of adherent cells on the membrane
      modified by adsorption of or covalent bonding with fibronectin reached 1 x 10(5)
      cells/cm(2) after 1 day of incubation, which corresponds to the confluent cell
      density in a conventional culture dish, while the cell densities on the membranes
      modifieds with gelatin and Pronectin were 1-5 x 10(4) cells/cm(2) and 0.5-1 x
      10(4) cells/cm(2), respectively. The loading of hydrodynamic shear force (0.23
      N/m(2)) for 30 min to the membranes bearing endothelial cells had little effect
      on the density of adhered cells. The membrane covalently bonded with fibronectin
      could well maintain a high cell density even after the loading of a higher shear
      force of 1.15 N/m(2) for 180 min, however, at this level of shear force 49% of
      adhered cells on the fibronectin-adsorbed membrane were lost after 30 min. A
      partial cardiopulmonary bypass in rats employing the hybrid artificial lung model
      composed of a polypropylene hollow fiber membrane covalently bonded with
      fibronectin and endothelial cell adhesion showed the inhibition of tumor necrosis
      factor-Alpha release and an increase in IL-10 concentration in the circulating
      blood compared with that employing an artificial lung without cells. Long-term
      partial cardiopulmonary bypass employing the hybrid artificial lung model should
      be studied further.

PMID- 14598109
TI  - Flow study on a newly developed impeller for a left ventricular assist device.
AB  - Nowadays, left ventricular assist devices are usually designed as high-speed,
      electric, rotary blood pumps. The pump drains blood from the left ventricular
      apex via an inlet cannula and ejects into the aortic root via an outlet conduit.
      To develop a high-performance pump, the present study utilizes partial
      differential equations to generate a surface representation of the impeller of
      the blood pump. Flow analysis around the impeller is performed by using the
      finite volume method to solve the fully incompressible three-dimensional Navier
      Stokes equations along with the k-epsilon turbulence model. The numerical results
      highlight flow features in the end-wall region of the pump, namely the clearance
      leakage cross-flow, and the vortex associated with this leakage. These secondary
      flows induce major energy losses in the pumping device. On the test study, a test
      loop was proposed to measure the performance characteristics. It was shown that
      the design would provide a flow rate of 4.4 l/min with a pressure head of 122
      mmHg. The DC motor power under these conditions was about 6 W and the rotational
      speed was 4500 rpm. Both the flow rate and head can satisfy the demand for the
      left artificial heart to work normally.

PMID- 14598110
TI  - Changes in surface roughness of erythrocytes due to shear stress: atomic force
      microscopic visualization of the surface microstructure.
AB  - Blood cells are subject to various kinds of stresses in flow fields. Hemolysis is
      the phenomenon in which a higher stress than normal damages the erythrocyte
      membrane and results in the leakage of its contents. Even if the stress is not
      strong enough to cause cell lysis, however, the cell membrane may sustain some
      damage. Therefore, to further improve the blood compatibility of artificial
      organs, the mechanisms of sublethal damage must be investigated. As a first step,
      we have analyzed the fine surface structure of sheared erythrocytes from a
      microscopic viewpoint by using an atomic force microscope (AFM) featuring nano
      meter-scale visualization. Sheep erythrocytes were sheared by a conventional
      cylindrical viscometer under sublethal shearing conditions. The duration of shear
      was set at 10 s, and the shearing rate was set at 0 (as control), 10000, and
      50000/s. After being stressed, the cell surfaces were visualized by an AFM and
      the surface roughness was measured. As a result, the roughness value was found to
      increase with the shearing rate: 4.5 +/- 1.5 nm (0/s, control), 6.9 +/- 2.1 nm
      (10000/s, P < 0.01), and 10.1 +/- 2.4 nm (50000/s, P < 0.01).

PMID- 14598111
TI  - Effect of pacing mode on sleep disturbance.
AB  - The relationship between pacing mode and sleep is not yet known, and therefore
      polysomnography was used to evaluate the effect. A total of 16 patients (8 men
      and 8 women; mean age, 72 +/- 9 years) with DDD pacemakers made up the study
      population. Of these 16 patients, 8 patients had complete AV block and 8 patients
      had sick sinus syndrome. The recording was done twice in VVI and DDD modes.
      Between VVI mode and DDD mode, sleep latency time (VVI mode: 38 +/- 25, DDD mode
      23 +/- 27 min), frequency of temporary waking (8.3 +/- 6.7, 3.7 +/- 2.9 times),
      the number of episodes of apnea (59 +/- 84, 36 +/- 55 times, the apnea-hypopnea
      index (AHI) (15 +/- 18, 10 +/- 13), and efficacy of sleep (72% +/- 10%, 81% +/-
      11%) were significantly different. Also, the apnea index improved significantly
      in DDD mode. There was no significant difference in total sleep time and in total
      duration of temporary waking between the two groups. From the study results, a
      reduction in sleep disturbance was achieved when DDD pacing mode was chosen,
      rather than VVI mode. Furthermore, efficacy of sleep also improved significantly
      compared with VVI mode. Interestingly, sleep apnea syndrome in four patients with
      AHI > or = 15 notably ameliorated when DDD mode was chosen; however, the
      mechanism involved in amelioration is still ambiguous and needs further
      assessment.

PMID- 14598112
TI  - Three-dimensional flow analysis of a mechanical bileaflet mitral prosthesis.
AB  - The Jyros (JR) and the Advancing The Standard (ATS) valves were compared with the
      St. Jude Medical (SJM) valve in the mitral position to study the effects of
      design differences, installed valve orientation to the flow, and closing sounds
      using particle tracking velocimetry and particle image velocimetry methods
      utilizing a high-speed video flow visualization technique to map the velocity
      field. Sound measurements were made to confirm the claims of the manufacturers.
      Based on the experimental data, the following general conclusions can be made: On
      the vertical measuring plane which passes through the centers of the aortic and
      the mitral valves, the SJM valve shows a distinct circulatory flow pattern when
      the valve is installed in the antianatomical orientation; the SJM valve maintains
      the flow through the central orifice quite well; the newer curved leaflet JR
      valve and the ATS valve, which does not fully open during the peak flow phase,
      generates a higher but divergent flow close to the valve location when the valve
      was installed anatomically. The antianatomically installed JR valve showed
      diverse and less distinctive flow patterns and slower velocity on the central
      measuring plane than the SJM valve did, with noticeably lower valve closing
      noise. On the velocity field directly below the mitral valve that is normal to
      the previous measuring plane, the three valves show symmetrical twin circulations
      due to the divergent nature of the flow generated by the two inclined half discs;
      the SJM valve with centrally downward circulation is contrasted by the two other
      valves with peripherally downward circulation. These differences may have an
      important role in generation of the valve closing sound.

PMID- 14598113
TI  - Development of a fluorinated polyimide hollow fiber for medical devices.
AB  - We fabricated an asymmetric polyimide hollow fiber for medical devices. A dry/wet
      phase inversion process was applied to a spinning process to prepare the hollow
      fiber. The outer diameter was 330 microm with a wall thickness of 70 microm.
      Transfer rates of O2 and CO2 in the asymmetric polyimide fiber were 6.9 x 10(-3)
      and 5.5 x 10(-3) cm3 (STP)/(cm2 s cmHg), respectively, which are approximately 10
      times higher than those measured in the Menox and Si-polypropylene fibers of the
      presently available membrane oxygenators. The blood compatibility of the
      polyimide hollow fiber was evaluated in vivo, indicating that polyimide had
      excellent blood compatibility when compared with silicone-coated fiber.
      Additionally, we fabricated a novel porous membrane with three-dimensional fine
      structure from cylindrical microscale pores and examined possibility of a porous
      membrane for use in hemodialysis.

PMID- 14598114
TI  - Effect of pore diameter of a porous membrane on progenitor cell content during
      membrane-separated coculture of hematopoietic cells and a stromal cell line.
AB  - The effect of pore diameter of a porous membrane on the progenitor cell content
      during a membrane-separated coculture of murine bone marrow hematopoietic cells
      and a murine stromal cell line, in which stromal cells adhered onto the lower
      surface of the membrane and hematopoietic cells were incubated on the upper
      surface of the membrane, was investigated in order to design a membrane
      bioreactor for ex vivo expansion of hematopoietic primitive cells employing
      exogeneic stromal cells. The hematopoietic progenitor cell [colony forming unit
      (CFU) Mix] content at 1 week in the membrane-separated coculture increased as the
      pore diameter of the membrane decreased from 12.0 to 0.4 microm. However, a
      further decrease in pore diameter from 0.4 to 0.1 microm did not affect the CFU
      Mix content. Observation of stromal cells that adhered on the lower surface of
      the porous membranes (0.4 and 3.0 microm pore diameters) under a confocal
      scanning microscope after staining with rhodamine phalloidin suggested that
      stromal cells can migrate to the membrane's upper surface through pores with a
      diameter greater than 3.0 microm. Consequently, membrane having small (< or = 0.4
      microm) pores that stromal cells could not pass through prevented direct contact
      between stromal and hematopoietic cells, which resulted in a higher content of
      hematopoietic progenitor cells (CFU-Mix) during the membrane-separated coculture.

PMID- 14598115
TI  - Characterization of a cultured dermal substitute composed of a spongy matrix of
      hyaluronic acid and collagen combined with fibroblasts.
AB  - The authors have developed an allogeneic cultured dermal substitute (CDS) through
      cultivation of fibroblasts on a two-layered spongy matrix of hyaluronic acid (HA)
      and atelocollagen (Col). The Col spongy layer is essential for attachment and
      proliferation of fibroblasts on the two-layered spongy matrix. The HA spongy
      layer is necessary for maintaining the moisture environment on the wound surface.
      The optimal weight ratio of HA/Col is determined by considering the following
      characteristics: mechanical properties for handling, cell viability after
      thawing, potency of vascular endothelial growth factor (VEGF) release after
      thawing, efficacy of wound healing, and manufacturing cost. This study is
      designed to investigate the physical properties for handling, the growth behavior
      of fibroblasts on the spongy matrix, and the quantitative analysis of VEGF
      released from fibroblasts in the fresh or cryopreserved CDS. The results of this
      study suggest that a CDS composed of Col spongy matrix alone has the highest
      potency in regard to the release of VEGF. However, taking into account the
      manufacturing cost, coupled with the potency of VEGF release, a two-layered
      sponge of HA and Col with a weight ratio of 5/2 is very promising for commercial
      application.

PMID- 14598116
TI  - Fundamental study of an electric power transmission system for implanted medical
      devices using magnetic and ultrasonic energy.
AB  - In this paper, the authors propose a novel electric power supply system for
      implanted medical devices. The system is noninvasive and uses two kinds of
      energy, magnetic and ultrasonic. The system can provide high power levels
      harmlessly. The energies are obtained by two types of vibrator, i.e., piezo and
      magnetostriction devices. A prototype was built and it was verified
      experimentally that the system is basically able to provide power. At high
      frequencies, such as 100 kHz, the output power was higher than the conventional
      system using a transformer. The normalized output power per unit volume also
      exceeded the transformer system.

PMID- 14598117
TI  - Recent advances in therapeutic apheresis.
AB  - Recent advances in therapeutic apheresis include technical improvements, new
      indications, and pathophysiological insights. A new device that adsorbs
      endotoxins onto immobilized human albumin from human whole blood was recently
      developed. In a prospective randomized controlled trial (endotoxin adsorber study
      EASY), apheresis-treated patients had more improved APACHE II scores than
      controls. In a prospective randomized trial, the Prosorba column containing
      immobilized staphylococcal protein A was tested against sham apheresis in
      patients with end-stage rheumatoid arthritis. A significant improvement occurred
      in 42% of the treated patients vs. 16% of the controls. Sudden hearing loss was
      treated in a prospective randomized trial by a single heparin-induced
      extracorporeal LDL precipitation (HELP) treatment in comparison with conservative
      therapy. In patients with elevated fibrinogen and/or low-density lipoprotein
      (LDL) cholesterol levels, HELP was significantly superior to 10 days of
      intravenous conventional treatment. Promising results were achieved in
      prospective randomized trials applying immunoadsorption in end-stage dilated
      cardiomyopathy and rheopheresis in age-related macular degeneration. In a
      noncontrolled trial, C4d-positive acute humoral rejection after kidney
      transplantation could be effectively treated by immunoadsorption. Finally, HELP
      apheresis was simplified by using new hardware (HELP-Futura). Direct adsorption
      of lipids (DALI)-LDL-apheresis was improved by testing DALI 1250 adsorbers with
      improved capacity. High-blood-flow DALI was shown to be safe and effective, with
      the advantage of reduced treatment time. Last but not least, a modification of
      dextran-sulfate cellulose LDL apheresis was developed for direct LDL
      hemoperfusion.

PMID- 14598118
TI  - Large-animal models of fulminant hepatic failure.
AB  - For the development of an artificial liver support system, a clinically relevant
      large-animal model of fulminant hepatic failure (FHF) is indispensable. Although
      several large-animal models have been reported so far, they have not been
      entirely satisfactory. Recently, we have developed a new porcine model of FHF by
      means of intraportal administration of 0.1 mg/kg of alpha-amanitin and 1
      microg/kg of lipopolysaccharide (LPS). This model has the following superior
      features: 100% mortality within 5 days along with a marked elevation of aspartate
      transaminase (AST) levels to around 10,000 IU/l, and severe metabolic disorders
      such as serum lactate accumulation, hypoglycemia, coagulopathy, plasma amino acid
      imbalance, and hyperammonemia; an onset of hepatic encephalopathy and a
      significant increase in intracranial pressure immediately before death; a
      reversal of FHF by orthotopic liver transplantation, proving that the toxicity is
      liver-specific and that the graft liver is unaffected; and the capability of the
      damaged liver to recover and achieve both morphological and functional
      regeneration in 1 week if supported by an efficient auxiliary graft. Because this
      porcine model satisfies many of the required criteria of an optimal FHF model, it
      is expected to provide a useful tool for the study of FHF and the development of
      new therapies.

PMID- 14598119
TI  - Preliminary study of a new type of energy transmission system for artificial
      hearts.
AB  - A transcutaneous energy transmission (TET) system is the most common way to power
      artificial hearts and ventricular assist devices. However, an external battery
      used with a TET system poses several problems, such as its heavy mass, small
      charge capacity, and long recharging time. The battery is indispensable when
      patients want to be ambulatory. This article proposes a new type of TET system
      that does not require an external battery because electrical energy is supplied
      remotely by using electromagnetic waves. For this system to operate, multiple
      transmitting antennas have to be mounted in a room or facility that has been
      shielded from electromagnetic waves, and a receiving antenna is attached to the
      patient. Electromagnetic waves transmit electrical power from the transmitting
      antennas to the receiving antenna. The received electrical power is sent to an
      implanted device through the TET system. The total power efficiency was plotted
      against the transmitter-receiver distance by measuring the power that was input
      to the transmitting antennas, and the final direct current (DC) power that was
      received by the receiving antenna. A 430-MHz frequency was applied in the
      experiments. The obtained efficiency was around 10% within a transmitter-receiver
      distance of 1 m when Yagi-Uda antennas were used for the transmitting antennas
      and two other types of antenna were used for the receiving antennas: a folded
      dipole with a reflector and a single loop with a reflector. The results suggested
      that the proposed system is worth considering. The proposed system would go a
      long way toward enhancing the patient's quality of life compared with the
      currently used conventional TET system.

PMID- 14598120
TI  - Vacuum-assisted venous drainage in single-access minimally invasive cardiac
      surgery.
AB  - This retrospective study evaluated the influence of vacuum-assisted venous
      drainage in single-access minimally invasive cardiac surgery. A total of 104
      patients who underwent cardiac surgery via minimal access incision were included
      in this study. Cardiopulmonary bypass was initiated with gravity alone, and
      vacuum-assisted venous drainage was applied only when the bypass flow was 2.2
      l/min/m2 or less. We compared intraoperative variables of the patients to whom
      vacuum-assisted venous drainage (vacuum group) was applied with those who
      underwent gravity venous drainage alone (gravity group). In the 13 patients who
      most recently underwent isolated valve operations without maze procedures, free
      hemoglobin was measured to evaluate hemolysis. Vacuum-assisted venous drainage
      was required in 77 (72.6%) patients. Except for a smaller body surface area in
      the gravity group (P = 0.0118), patient characteristics did not differ
      significantly between the two groups. Free hemoglobin 60 mins after the beginning
      of cardiopulmonary bypass was higher in the vacuum group than in the gravity
      group (21.5 +/- 7.3 vs 11.1 +/- 7.1 mg/dl, P = 0.0284). Operative mortality and
      morbidity did not differ significantly between the groups. We found vacuum
      assisted venous drainage to be a safe, simple, and effective technique in cases
      of minimally invasive cardiac surgery. However, there is a potential risk of
      hemolysis and air embolism, as shown in our findings and previous reports.

PMID- 14598121
TI  - In vivo evaluation of the pulsatile ECLS system.
AB  - Extracorporeal life support (ECLS) systems have been increasingly applied to
      groups of patients with cardiorespiratory failure, including pediatric and adult
      patients with respiratory failure. Current pulsatile ECLS systems use a single
      pulsatile blood pump that generates a high inlet pressure in the membrane
      oxygenator. To minimize this high inlet pressure, we have developed a new and
      improved ECLS system, twin pulse life support (T-PLS). To analyze the advantages
      of T-PLS, we have compared T-PLS with a single pulsatile ECLS system. An acute
      heart failure model was constructed by using a pulmonary artery banding
      technique. Fourteen pigs (22-31 kg) were used, with cardiac outputs of 2.0 l/min
      and a V/Q ratio set at 1. Cannulae of 28 Fr and 18 Fr were used in the right
      atrium and aorta, respectively. A polypropylene hollow-fiber membrane oxygenator
      and four polymer valves 30 mm in diameter were used in the T-PLS system. In the
      single pulsatile ECLS system, Medtronic Hall monostrut valves were used. To
      evaluate blood cell trauma in both pulsatile ECLS systems, plasma free hemoglobin
      (fHb) was measured while the systems were in use. The results show that fHb
      levels in T-PLS are lower than fHb levels in the single pulsatile ECLS system.
      There is a possibility that T-PLS could be used as an ECLS system for emergency
      situations.

PMID- 14598122
TI  - Long-term results of mitral valve replacement: biological xenograft versus
      mechanical valves.
AB  - We studied 279 patients who underwent mitral valve replacement at the Department
      of Thoracic and Cardiovascular Surgery, Hyogo College of Medicine, between
      November 1973 and December 1998. The patients were divided into two groups based
      on the type of replacement valve (154 patients in the biological xenograft group
      and 125 patients in the mechanical valve group), and the long-term results were
      compared. Clinically satisfactory results were obtained in both the biological
      xenograft group and the mechanical valve group according to the surgical results,
      long-term survival, and incidence of prosthetic valve endocarditis. At 15 years,
      fewer patients in the mechanical valve group than in the biological xenograft
      group were free of bleeding events (92.5 +/- 3.7% vs 100% P < 0.05). At 15 years,
      the biological xenograft group was lower than the mechanical valve group with
      respect to freedom from thromboembolism (72.2 +/- 4.6% vs 93.5 +/- 3.6% P <
      0.01), freedom from valve failure (22.0 +/- 5.2% vs 87.0 +/- 4.1% P < 0.005) and
      freedom from cardiac events (16.5 +/- 3.9% vs 47.2 +/- 14.5% P < 0.01). Though it
      has previously been suggested that biological xenografts used in mitral valve
      replacement do not need anticoagulation, the current study suggests the need for
      anticoagulation with the use of biological xenografts. Mechanical valves require
      close monitoring of anticoagulation, but their use has decreased the incidence of
      valve failure and thromboembolism, as compared with the use of biological
      xenografts. Therefore, mechanical valves are currently the preferred choice for
      mitral valve replacement. We believe that biological xenografts are indicated
      only for the older patient (> or =65 years).

PMID- 14598123
TI  - Closing behavior of the mechanical heart valve in a total artificial heart.
AB  - Recently, cavitation on the surface of mechanical heart valves has been studied
      as a cause of fractures occurring in implanted mechanical heart valves. The cause
      of cavitation in mechanical heart valve was investigated in both 25-mm Bjork
      Shiley and 25-mm Medtronic Hall valves. The closing events of these valves in the
      mitral position were simulated in an electrohydraulic total artificial heart with
      a stroke volume of 85 ml. The tests were conducted under physiologic pressures at
      heart rates of 60, 70, 80, and 90 beats/min with cardiac outputs of 4.5, 5.5,
      6.4, and 7.5 l/min, respectively. The disk closing behavior was measured by a
      laser displacement sensor. The closing behaviors were investigated under various
      atrial and aortic pressures. In both valves, the duration of closing decreased
      with an increase in the cardiac output. The greater the amount of atrial
      pressure, the shorter the closing duration of both valves. The maximum closing
      velocity of the Medtronic Hall monostrut valve ranged from 0.8 to 0.9 m/s, and
      that of the Bjork-Shiley monostrut valve ranged from 0.73 to 0.78 m/s. In both
      valves, the maximum closing velocities were less than the reported cavitation
      thresholds. This suggests that there should be no possibility of occurrence of
      cavitation in an electrohydraulic total artificial heart with mechanical heart
      valve.

PMID- 14598124
TI  - Impact of convective transport on dialyzer clearance.
AB  - The results of predictions of three mathematical models used to describe the
      impact of convective flow on dialyzer clearance are presented. These models are
      based on the ordinary differential equations, which describe changes of solute
      concentration and solute and fluid flows along the module length. One of the
      models takes into consideration the existence of the boundary layers on both
      sides of the membrane wall, by including in the equations two parameters kB and
      kD, which describe mass transport coefficients in blood and dialysate,
      respectively. In the second model, the boundary layers are included in one lumped
      membrane permeability parameter. The diffusive membrane permeability was
      calculated from pure diffusive clearance, which was taken from experimental
      results. In the third model, a linear dependence of transmittance coefficient and
      ultrafiltration flow was proposed. The theoretical results were compared with
      data obtained in experiments carried out in vitro with four types of high-flux
      hollow-fiber dialyzers. The comparisons demonstrate that the first two models are
      of similar accuracy and the third model is not suitable for small solutes.

PMID- 14598125
TI  - Experimental proof of contamination of blood components by (1-->3)-beta-D-glucan
      caused by filtration with cellulose filters in the manufacturing process.
AB  - The level of (1-->3)-beta-D-glucan in blood is a diagnostic index of fungal
      infection because it is released from the fungal cell wall. However, high levels
      of plasma (1-->3)-beta-D-glucan in patients administered blood components may
      give false positive results. High levels of (1-->3)-beta-D-glucan have been
      detected in blood components. We suspected that (1-->3)-beta-D-glucan from
      cellulose filters had been eluted into blood components by filtration in the
      manufacturing process. To investigate the contamination of blood components by (1
      ->3)-beta-D-glucan from cellulose filters, in vitro experiments were performed by
      using six cellulose filters and a nylon filter. Human serum albumin (HSA)
      solution (100 ml) was flowed through each filter after rinsing with 100 ml of
      distilled water, and (1-->3)-beta-D-glucan in each fraction was determined by
      Fungitec G test MK. The concentration of (1-->3)-beta-D-glucan eluted from
      cellulose filters in 100-ml distilled water fractions ranged from 6 to 207 pg/ml,
      and that of HSA fractions ranged from 33 to 20,784 pg/ml. These data showed that
      remarkably higher (1-->3)-beta-D-glucan levels were detected in HSA fractions
      flowed through cellulose filters in spite of advance rinsing with 100 ml of
      distilled water. In the case of a nylon filter, (1-->3)-beta-D-glucan was not
      eluted in either fraction. These results indicate that (1-->3)-beta-D-glucan
      contamination in blood components is caused by filtration with cellulose filters
      in the manufacturing process.

PMID- 14598126
TI  - Strict glycemic control in diabetic dogs with closed-loop intraperitoneal insulin
      infusion algorithm designed for an artificial endocrine pancreas.
AB  - The ultimate goal of the development of an artificial endocrine pancreas is to
      achieve long-term strict glycemic regulation. To establish the physiological
      insulin delivery route of the artificial endocrine pancreas, intraperitoneal
      insulin infusion may be important. For this purpose, we tried to develop a closed
      loop intraperitoneal insulin infusion algorithm by analyzing the pharmacokinetics
      of intraperitoneal regular insulin absorption using a mathematical model. The
      parameters for this algorithm were calculated to simulate the plasma insulin
      profile after intraperitoneal insulin injection as closely as possible. To
      evaluate the appropriateness of this algorithm, we tried glycemic control after
      an oral glucose load of 2 g/kg or a meal load of 80 kcal/kg in diabetic dogs by
      applying the algorithm. With the use of the subcutaneous insulin lispro infusion
      algorithm, which we have previously reported, alloxan-induced diabetic dogs
      exhibited postprandial hyperglycemia and delayed hyperinsulinemia, followed by
      hypoglycemia after an oral glucose load of 2 g/kg. However, by using the
      intraperitoneal insulin infusion algorithm, excellent glycemic control
      (postprandial blood glucose levels of 9.1 +/- 0.8 mmol/l at 70 min and 3.8 +/-
      0.3 mmol/l at 240 min, respectively) could be achieved without any associated
      delayed hyperinsulinemia or hypoglycemia. Glycemic excursion after a meal load of
      80 kcal/kg was also controlled from 3.9 to 10.1 mmol/l. Our results confirm that
      the intraperitoneal insulin infusion algorithm in vivo is feasible and that this
      algorithm can be superior to the subcutaneous insulin lispro infusion algorithm
      in the regulation of blood glucose.

PMID- 14598127
TI  - Spongy matrix of hyaluronic acid and collagen as a cultured dermal substitute:
      evaluation in an animal test.
AB  - The authors have developed a two-layered spongy matrix composed of hyaluronic
      acid (HA) and atelo-collagen (Col) as a cultured dermal substitute (CDS). This
      spongy matrix was applied to a full-thickness skin defect on the dorsum of
      Sprague-Dawley rats, and the wound conditions were observed over a period of 2
      weeks. A piece of two-layered spongy matrix was applied to the wound, over which
      a commercially available polyurethane film dressing was applied. Both the
      macroscopic and the histological evaluations indicate that the two-layered spongy
      matrix is able to prepare a highly vascularized granulation tissue at an early
      stage. These findings suggest that this type of spongy matrix would be useful as
      a CDS.

PMID- 14598128
TI  - Metal allergy to stainless steel wire after coronary artery bypass grafting.
AB  - To our knowledge, this is the first reported case of a manganese metal allergy to
      stainless steel wire. A 51-year-old man suffered from a refractory pruritic
      erythematous wheal after the insertion of a stainless steel wire. The patch test
      showed strong reactions to manganese, one of the constituents of stainless steel
      wire. After the removal of all stainless steel wires, the symptoms were much
      improved, except for mild pruritus on his face.

PMID- 14598129
TI  - Oral microbial biofilms and plaque-related diseases: microbial communities and
      their role in the shift from oral health to disease.
AB  - Many oral pathologies, such as dental caries, periodontal disease and peri
      implantitis are plaque-related. Dental plaque is a microbial biofilm formed by
      organisms tightly bound to a solid substrate and each other by means of an
      exopolymer matrix. Bacteria exhibit different properties when contained within a
      biofilm. Knowing the mechanisms controlling the formation and development of
      biofilms can help to understand the emergence and progression of such pathologies
      and to plan effective treatment. Most periodontal pathogens are common
      saprophytes of the oral cavity, expressing their virulence only in a susceptible
      host or when some changes come about in the oral environment. Physical, metabolic
      and physiological interactions may cause positive or negative effects among the
      various microbiota present. Such mechanisms of antagonism/synergy select the
      bacterial population and alterations of its composition affect the balance with
      the host and may lead to pathology. The effectiveness of antimicrobial agents, as
      measured through in vitro tests, is dramatically reduced in vivo due to the
      properties of the microbial community: mature, intact biofilms are less sensitive
      to such agents, as the exopolymer matrix, bacterial enzymes and slow growth rate
      hinder the action of chemotherapeutic agents. The present literature review aims
      to examine the most representative studies, focusing on the characteristics of
      bacterial communities and the crucial shift from oral health to plaque-related
      diseases.

PMID- 14598130
TI  - Calcitonin gene-related peptide immunoreactive neurons with dichotomizing axons
      projecting to the lumbar muscle and knee in rats.
AB  - Dorsal root ganglion (DRG) neurons with dichotomizing axons have been reported in
      several species and are thought to be related to referred pain. However, these
      neurons, which have dichotomizing axons to the lumbar muscles and to the knee,
      have not been investigated. Clinically, pain from the lumbar muscles is sometimes
      referred to the lower extremities. Two kinds of neurotracers [1,1'-dioctadecyl
      3,3,3',3'-tetramethyl-indocarbocyanine perchlorate (DiI) and fluoro-gold (FG)]
      were used in the present double-labelling study. DiI crystals were placed in the
      left lower back muscle, and FG was applied to the medial side of the knee.
      Bilateral DRGs from L1 through L6 were immunoreacted with calcitonin gene-related
      peptide (CGRP) antibodies and observed under a fluorescence microscope. DRG
      neurons double-labelled with DiI and FG were recognized only in the ipsilateral
      DRGs from levels L1 to L6. Approximately 1% of DRG neurons innervating the low
      back muscles had other axons to the medial side of the knee. In double-labelled
      neurons, the ratio of CGRP-immunoreactive DRG neurons was 60%. This finding
      provides a possible neuroanatomical explanation for referred knee pain from the
      lower back since CGRP is a marker of sensory neurons typically involved with pain
      perception. However, these neurons are rare, and mechanisms of referred pain may
      be explained by the convergence-projection hypothesis.

PMID- 14598131
TI  - Development, persistence and regeneration of foraging ectomycorrhizal mycelial
      systems in soil microcosms.
AB  - Development of extraradical mycelia of two strains each of Paxillus involutus and
      Suillus bovinus in ectomycorrhizal association with Pinus sylvestris seedlings
      was studied in two dimensions in non-sterile soil microcosms. There were
      significant inter- and intra-specific differences in extraradical mycelial growth
      and morphology. The mycelial systems of both strains of P. involutus were diffuse
      and extended more rapidly than those of S. bovinus. Depending on the strain, P.
      involutus mycelia were either highly plane filled, with high mass fractal
      dimension (a measure of space filling) or sparse, low mass fractal dimension
      systems. Older mycelial systems persisted as linear cords interlinking
      ectomycorrhizal tips. S. bovinus produced either a mycelium with a mixture of
      mycelial cords and diffuse fans that rapidly filled explorable area, or a
      predominately corded mycelium of minimal area cover. In the soil microcosms, mass
      fractal dimension and mycelial cover tended to increase with time, mycelia
      encountering litter having significantly greater values. Results are discussed in
      terms of the ecology of these fungi, their foraging activities and functional
      importance in forest ecosystems.

PMID- 14598132
TI  - Biliary cystic disease: the risk of cancer.
AB  - Congenital choledochal cysts carry a risk of cancer, probably as a result of a
      sequence of pancreatobiliary reflux, inflammation, dysplasia with or without
      intestinal metaplasia, and invasive carcinoma. A combination of biliary stasis
      due to poor drainage of a stagnant pool of bile and increased mutagenicity of the
      bile acids may be ultimately responsible. There is very frequently an anomalous
      pancreato-biliary ductal junction, and the reflux of pancreatic juice into the
      bile duct is thought to play a central role in the process of carcinogenesis. The
      risk of cancer is low in childhood (under 1% in the first decade), but shows a
      clear increase with age (over 10% in the third decade). The implication for
      management is that total excision of the extrahepatic biliary tree at risk
      remains the gold standard for management of these cysts, and simple bypass in
      infancy or childhood leaves the risk of cancer, though possibly diminished, still
      significant.

PMID- 14598133
TI  - Classification of congenital biliary cystic disease: special reference to type Ic
      and IVA cysts with primary ductal stricture.
AB  - Congenital biliary cysts occur not only in the choledochus but also everywhere in
      the biliary tree, and are frequently accompanied by pancreatobiliary malunion.
      Alonso-Lej and colleagues first classified choledochal cysts into three types, in
      1959. Due to the recognition of intrahepatic involvement, we refined their
      classification into six types, in 1977, and this has become the reference.
      However, this classification does not include the concept of pancreatobiliary
      malunion and has caused some confusion, especially in regard to types Ic and IVA.
      Type Ic, showing fusiform dilatation, has a pancreatobiliary malunion and often
      extends continuously to the intrahepatic duct. Type IVA, with intrahepatic
      involvement, shows primary ductal stricture, especially around the hepatic hilum
      and umbilicus. The incidence of the stricture is considerably greater than was
      previously assumed, and upstream intrahepatic ducts often join the dilated duct,
      with distinct caliber change. Intrahepatic dilatation may develop primarily, due
      to the stricture, combined with weakness of the duct wall. This stricture can be
      corrected by portal dissection in the liver to obtain a large anastomosis. In
      patients with intrahepatic involvement, we should carefully find the stricture by
      suitable cholangiograms, or by intraoperative cholangioscopy. Detecting the
      ductal stricture is obviously important, rather than classifying the cyst as type
      Ic or IVA.

PMID- 14598134
TI  - Pancreaticobiliary maljunction: retrospective and nationwide survey in Japan.
AB  - Pancreaticobiliary maljunction (PBM) is a congenital anomaly defined as a union
      of the pancreatic and biliary duct that is located outside the duodenal wall. The
      Japanese Study Group on Pancreaticobiliary Maljunction and the Committee for
      Registration enrolled and analyzed 1627 patients with PBM who had been diagnosed
      and treated from January 1, 1990 to December 31, 1999 at 141 hospitals throughout
      the country. There were 1239 patients with dilatation of the bile duct (group A)
      and 388 patients without dilatation (group B). The average age was 24 years in
      group A and 47 years in group B; the age was significantly higher in group B. The
      type of confluence between the terminal choledochus and the pancreatic duct has
      been classified into three types (type a, right-angle type; type b, acute-angle
      type; and type c, complex type). In group A, type a accounted for 57.9% and was
      significantly more frequent compared with the other types (type b, 32.4%; type c,
      5.6%). In group B, type b accounted for 60.8%, being significantly more frequent
      compared with the other types (type a, 29.4%; type c, 7.2%). Subjective symptoms,
      preoperative complications (e.g., liver dysfunction and acute pancreatitis),
      pancreatic stone, and pancreatic duct morphological abnormality were
      significantly more frequent in group A. However, the amylase levels in the bile
      and gallbladder were significantly higher in group B, and the presence of
      gallstone and morphological abnormality of the gallbladder was significantly more
      frequent in group B. The occurrence rate of cancer in the biliary tract was 10.6%
      in group A and 37.9% in group B, being significantly higher in group B. In group
      A, cancer of the extrahepatic bile duct was seen in 33.6% and cancer of the
      gallbladder was seen in 64.9%, but gallbladder cancer was present significantly
      more frequently in the patients with diffuse or cylindrical dilatation, and bile
      duct cancer was present significantly more frequently in the patients with cystic
      dilatation. In group B, 93.2% of the patients had gallbladder cancer, and bile
      duct cancer was found in as few as 6.8%. Against this background Japanese
      surgeons regard cholecystectomy, resection of the extrahepatic bile duct, and
      hepaticojejunostomy as standard operations for PBM with dilatation of the bile
      duct. However, opinion on whether or not the bile duct should be removed in the
      treatment of PBM without dilatation of the bile duct has been divided among
      Japanese surgeons. A randomized controlled trial is necessary.

PMID- 14598135
TI  - Surgical treatment of choledochal cysts.
AB  - Biliary cystic disease is uncommon in Asia and very rare in Europe and the
      Americas. Patients with biliary cysts may present as infants, children, or
      adults. When patients present as adults, they are more likely to have stones in
      the gallbladder, common duct, or intrahepatic ducts and to present with biliary
      colic, acute cholecystitis, cholangitis, or gallstone pancreatitis. With
      increasing age at presentation, the risks of intrahepatic strictures and stones,
      segmented hepatic atrophy/hypertrophy, secondary biliary cirrhosis, portal
      hypertension, and biliary malignancy all increase significantly. Factors to be
      considered when performing surgery on patients with biliary cystic disease
      include: (1) age, (2) presenting symptoms, (3) cyst type, (4) associated biliary
      stones, (5) prior biliary surgery, (6) intrahepatic strictures, (7) hepatic
      atrophy/hypertrophy, (8) biliary cirrhosis, (9) portal hypertension, and (10)
      associated biliary malignancy. In general, regardless of age, presenting
      symptoms, biliary stones, prior surgery or other secondary problems, surgery
      should include cholecystectomy and excision of extrahepatic cyst(s). With respect
      to the distal bile duct, the surgical principle should be excision of a portion
      of the intrapancreatic bile duct with care to not injure the pancreatic duct or a
      long common channel. Resection of the pancreatic head should be reserved for
      patients with an established malignancy. With respect to the intrahepatic ducts,
      surgery should be individualized depending on whether (1) both lobes are
      involved, (2) strictures and stones are present, (3) cirrhosis has developed, or
      (4) an associated malignancy is localized or metastatic. When the liver is not
      cirrhotic, hepatic parenchyma should be preserved even when strictures and stones
      are present. If cirrhosis is advanced, hepatic transplantation may be indicated,
      but this sequence of events is unusual. If a malignancy has developed, oncologic
      principles should be followed. Whenever possible, resection of a localized tumor
      including adjacent hepatic parenchyma and regional lymph nodes should be
      performed.

PMID- 14598136
TI  - MR-guided percutaneous cryotherapy of malignant liver tumor under horizontal
      magnetic open system: initial experience.
AB  - BACKGROUND/PURPOSE: We describe the feasibility and accuracy of magnetic
      resonance (MR)-guided cryotherapy for malignant liver tumor, using a horizontal
      magnetic open system. METHODS: Using an MR-compatible cryotherapy system and
      horizontal-magnetic open-configuration MR scanner, we performed percutaneous
      cryotherapy for four malignant liver tumors. RESULTS: All procedures were carried
      out safely and accurately without any serious complication. Residual tumor was
      observed in one patient with metastatic liver tumor located directly under the
      diaphragm. CONCLUSIONS: MR-guided cryotherapy appears to be ideal and desirable
      as a minimally invasive therapy for liver tumor.

PMID- 14598137
TI  - Ductal drainage with head coring in chronic pancreatitis with small-duct disease.
AB  - PURPOSE: To assess prospectively the feasibility of drainage procedures in
      patients with chronic pancreatitis and small ducts. METHODS: Forty-five patients
      with chronic pancreatitis and main pancreatic ductal diameters less than 5 mm
      (group 1) underwent lateral pancreaticojejunostomy with varying degrees of head
      coring. Their outcomes were recorded and compared with 212 patients who had large
      ducts (diameter >7 mm; group 2). Patients in the two groups were comparable in
      age, etiology, presence of jaundice, diabetes, steatorrhea, head mass,
      pseudocysts, and biliary obstruction. RESULTS: Mortality and complication rates
      were similar in the two groups. Drainage procedures relieved pain in 94% (43/45
      cases) in small-duct disease, and 91% (193/212) of cases with large-duct disease
      over a median follow-up greater than 30 months. Functional results were also
      comparable. CONCLUSION: In the light of these results, drainage procedures merit
      wider application for small-duct disease.

PMID- 14598138
TI  - Pancreatic pseudocysts: 10 years of experience.
AB  - BACKGROUND: Pancreatic pseudocysts (PP) are considered to be one of the major
      complications of acute, chronic, and posttraumatic pancreatitis. Their treatment
      has always been a surgical challenge. Surgical treatment was for many years the
      only choice in the management of PP. However, technological development has
      provided new alternatives in their management. PURPOSE: The purpose of this
      retrospective study is to present our experience in the treatment of PP and to
      define the criteria for the selection of the treatment method. METHODS: During
      the past decade, 14 patients were treated for PP in our clinic. We classified our
      patients in three groups based on the treatment: A, conservative treatment; B,
      surgical treatment with internal drainage; and C, percutaneous external drainage
      (PED) under CT guidance. RESULTS: Conservative treatment had excellent outcome
      when it was applied in patients with small cysts. Internal drainage was always
      successful, but patients needed more hospitalization and showed increased
      morbidity compared to PED. PED was successful in two of three patients.
      CONCLUSIONS: Conservative treatment is a good choice for small asymptomatic
      cysts, particularly for patients who are poor candidates for operation. Internal
      drainage is a good method of treatment and should be used as the first choice by
      experienced surgeons. Finally, PED is a good first choice for patients with a
      unilocular cyst and contraindications for surgery.

PMID- 14598139
TI  - Intrahepatic segmental bile duct patterns in hepatolithiasis: a comparative
      cholangiographic study between Taiwan and Japan.
AB  - BACKGROUND/PURPOSE: We analyzed confluence patterns of intrahepatic segmental
      bile ducts, seeking to relate hepato-lithiasis to anatomic variation. The
      comparative study was completed patients with hepatolithiasis in Taiwan and
      Japan. METHODS: Direct cholangiography was performed in 103 hepatolithiasis
      patients in Taiwan and 77 in Japan. Segmental ducts patterns were classified as
      type I, normal configuration; type II, "triad" confluence; type III, posterior
      segmental duct joining left hepatic duct; or type IV, distal confluence of the
      right posterior segmental duct. RESULTS: Taiwanese patients had only calcium
      bilirubinate or black stones, and were mostly female. As overall analysis, types
      I, II, III, and IV were found in 61, 26, 13, and 3 patients, respectively. In
      Japanese, types I, II, III, and IV were found in 52, 10, 13, and 2, respectively.
      There was no difference between the two institutes. Since no patients in Taiwan
      had cholesterol calculi, Japanese patients were reanalyzed including only 58
      patients with calcium bilirubinate or black stones. Differences in those
      populations remained insignificant. CONCLUSION: Anatomic variations in segmental
      ducts apparently do not contribute to pathogenesis of hepatolithiasis.

PMID- 14598140
TI  - Laparoscopic resection for nonfunctioning small glucagon-producing tumor: report
      of a case and review of the literature.
AB  - Glucagonoma is a relatively rare type of pancreatic endocrine tumor, and is often
      well-developed and malignant at detection. We report a case of nonfunctioning
      small glucagon-producing tumor that was successfully resected by laparoscopic
      surgery. A 63-year-old woman was admitted to our hospital for further examination
      of a pancreatic tumor that had been detected incidentally. Hematological data and
      hormone concentrations were within normal ranges. Abdominal ultrasonography and
      computed tomography showed a small mass in the body of the pancreas. Laparoscopic
      distal pancreatectomy was done. Macroscopically, the resected tumor was a
      yellowish-white, solid mass measuring 8 x 8 x 7 mm. The tumor cells showed
      positive immunohistochemical staining for chromogranin A and glucagon. The
      postoperative course was uneventful. To the best of our knowledge, this is the
      first report of laparoscopic surgery for a nonfunctioning small glucagon
      producing tumor. Because of recent improvements in laparoscopic surgery
      technique, use of this approach for resection of pancreatic benign small
      endocrine tumors will likely increase in the future.

PMID- 14598141
TI  - Urgent Whipple resection for solid pseudopapillary tumor of the pancreas.
AB  - We report a 14-year-old boy who was urgently transferred to our institution after
      a blunt abdominal trauma. CT scan and repeated ultrasound examinations revealed a
      subhepatic mass, which slowly increased in size. Imaging features were not
      specific enough to permit a precise diagnosis. Because of the positive peritoneal
      signs and increased signs of circulatory instability, the decision was made to
      perform an urgent explorative laparotomy. The exploration revealed that the large
      haematoma-like bleeding mass was a tumor arising from the head of the pancreas,
      which ruptured on the surface. We performed a curative R0 Whipple resection.
      Histology of the resected specimen revealed a solid pseudopapillary tumor of the
      pancreas, an extremely rare tumor predominantly occurring in young and middle
      aged women. It has a favorable prognosis if resected radically. The boy is well
      30 months after the operation. To our knowledge, there are only two other
      descriptions of pancreatic solid pseudopapillary tumor in boys treated urgently
      by Whipple resection because of acute presentation after blunt abdominal trauma.

PMID- 14598142
TI  - Biliary papillomatosis: report of seven cases and review of English literature.
AB  - Biliary papillomatosis is rare. Before 1993, there were only 21 cases reported in
      the English literature. This article reports our experience in managing this
      disease and reviews experiences from recent English literature. A retrospective
      review of patients with biliary papillomatosis was conducted in our institution.
      A search of the English literature between 1993 and 2002 was performed in the
      MEDLINE database using "biliary papillomatosis" as the keyword. Seven patients
      with biliary papillomatosis were treated in our hospital. Another 50 cases were
      reported in the recent literature. This amounted to a total of 78 cases so far
      reported. The male to female ratio was approximately 2 : 1. The mean age at
      presentation was 63 years. Most patients presented typically with cholangitis.
      Malignant change was present in 33 patients (42%). Concomitant intrahepatic and
      extrahepatic disease was noticed in 33 patients (42%). The overall resection rate
      was 55%. The mean survival was 28 months following resection, irrespective of
      histological type. Patients without tumor resection had a poorer survival of less
      than 11 months. Biliary papillomatosis presents typically with biliary
      obstruction and it occurs most often in elderly males. Resection is recommended
      because of the considerable malignancy rate, diffuse pattern of disease, and
      better survival following curative surgery. Malignant histology is not always
      associated with a poorer prognosis provided that radical resection can be
      achieved.

PMID- 14598143
TI  - Sphincter of Oddi dysfunction and the anomalous pancreaticobiliary junction.

PMID- 14598144
TI  - Extended hepatic resection and outcomes in intrahepatic cholangiocarcinoma.
AB  - BACKGROUND/PURPOSE: The aim of this report was to assess the outcome of
      aggressive surgical treatment for intrahepatic cholangiocarcinoma. METHODS: From
      1984 to 2001, we encountered 64 patients with intrahepatic cholangiocarcinoma. Of
      the 64 patients, 50 patients who underwent surgical resection with
      macroscopically curative objectives (78%) were reviewed for surgical procedures
      and outcomes. RESULTS: Hemi- or more extensive hepatectomy was required for
      surgical resection in 40 patients (80%). Overall hospital morbidity and mortality
      rates were 50% and 8%, respectively. Curative resection with pathological free
      margins was achieved in 34 patients (68%). The 1-, 3-, and 5-year patient
      survival and tumor-free survival rates were 61.6%, 37.6%, and 22.5%; and 55%,
      11%, and 11%, respectively. Among the macroscopic types, all 9 patients with
      intraductal growth type are alive 11-75 months after surgery. Survival rates
      among patients who had undergone curative resection were significantly better
      than those in patients who had undergone noncurative resection, even when
      patients with the intraductal growth type were excluded. Nodal status did not
      affect patient survival. CONCLUSIONS: Although the overall survival rate after
      surgical resection remains unsatisfactory, long-term survival is possible through
      extended surgical resection with pathological free margins. Patients with the
      intraductal growth type of intrahepatic cholangiocarcinoma might have the best
      chance of being cured by surgical treatment.

PMID- 14598145
TI  - Anatomic and molecular pathology of intrahepatic cholangiocarcinoma.
AB  - Intrahepatic cholangiocarcinoma (ICC) is the second most common malignant tumor
      of the liver, and ICC is reportedly increasing recently. ICC is usually
      adenocarcinoma with variable desmoplastic reaction, although there are several
      special or unusual histological features. ICC may arise at the large intrahepatic
      bile duct near the hepatic hilus and also from the bile ductules at the border of
      the hepatic parenchyma. On the anatomical level, the pathology of ICC differs
      depending on the region from which the ICC arises. At the large intrahepatic bile
      duct, ICC presents papillary growth and periductal infiltration. Some cases show
      extensive papillary growth and intraluminal spread with marked gastroenteric
      metaplasia. Mucus core protein 1 is expressed in aggressive ICC. ICC arising from
      ductules shares phenotypes of hepatocellular carcinoma. ICC in chronic biliary
      diseases, particularly arising in hepatolithiasis, presents precancerous lesions
      that include biliary epithelial dysplasia, as well as in-situ carcinoma. Chronic
      advanced hepatitis C is one of the background diseases of ICC. Chronic
      inflammation, with the upregulation of cyclooxygenase-2 and growth factors, and
      the formation of reactive oxygen species are one of the causative factors in the
      DNA damage of biliary epithelial cells. K- ras mutation and aberrant expression
      of p53 are found in one-third of ICCs. The latter may be due to mdm-2
      upregulation. Hepatocyte growth factor/met and interleukin 6 (IL6)/IL6 receptor
      are involved in cell proliferation/mitoinhibition and apoptosis in ICC. Fibrous
      stroma formation and invasion involve the proliferation of Alpha-smooth muscle
      antigen-positive stromal cells, and cell-to-cell and cell-to-matrix interactions
      involving E-cadherin/catenin and CD44 and matrix proteinases may be involved in
      the invasion of ICC. Evasion of immune surveillance involving the Fas/FasL system
      is important in the malignant progression of ICC. Further molecular and genetic
      studies are mandatory to evaluate the pathogenesis and progression of ICC.

PMID- 14598146
TI  - Intrahepatic cholangiocarcinoma: indication for transplantation.
AB  - BACKGROUND/PURPOSE: Cholangiocarcinoma (CCC) is a rare malignant tumor of the
      biliary system with a poor prognosis that frequently presents in advanced
      unresectable stages. A discussion of the role of liver transplantation (LTx) for
      intrahepatic (IH)-CCC will be presented, based on a review of the international
      literature. METHODS: A search of the international literature related to the
      topic was performed in the established online databases and databanks. Only those
      reports with patient series larger than ten were included. RESULTS: The largest
      series of patients with IH-CCC ( n = 186) was reported in the Data Analysis
      Booklet of the European Liver Transplant Registry (ELTR), revealing 1-, 3-, 5-, 8
      , and 10-year survival rates of 58%, 38%, 29%, 23%, and 21%. Other single-center
      series had comparable or even worse outcomes. More recent experience identified a
      certain highly selected group of patients who could benefit from LTx in an
      otherwise unresectable state of disease. Several single-center studies found
      tumor stage or size, lymph node involvement, and positive surgical
      margins/contiguous organ infiltration to be predictors of outcome. The recently
      published Mayo Clinic protocol uses preoperative chemoirradiation and staging at
      laparotomy before proceeding to liver transplantation, resulting in an early
      experience with 100% 1-year survival. CONCLUSIONS: Generally speaking, IH-CCC is
      not a favorable indication for liver transplantation. However, there is a highly
      selected group of patients with early tumor stages potentially benefitting from
      LTx. Combination with neoadjuvant chemoirradiation may further improve results
      after LTx. Living-donation LTx may open new therapeutic possibilities to treat
      patients at an early stage of disease.

PMID- 14598147
TI  - Intrahepatic cholangiocarcinoma: macroscopic type and stage classification.
AB  - The Liver Cancer Study Group of Japan established a classification of macroscopic
      type and the TNM staging of intrahepatic cholangiocarcinoma (ICC). With the
      observation of more than 240 resected cases of ICC, three fundamental types were
      established. They were: (1) mass-forming (MF) type, (2) periductal-infiltrating
      (PI) type, and (3) intraductal growth (IG) type. The MF type forms a definite
      mass, located in the liver parenchyma. The PI type is defined as ICC which
      extends mainly longitudinally along the bile duct, often resulting in dilatation
      of the peripheral bile duct. The IG type proliferates toward the lumen of the
      bile duct papillarily or like a tumor thrombus. The TNM classification of ICC was
      then designed, using 136 cases of the MF type resected curatively between 1990
      and 1996 at member institutes. Univariate and multivariate analyses showed: (1)
      tumor 2 cm or less, (2) single nodule, and (3) no vascular and serous membrane
      invasion as prognostic factors. T factors were defined as follows: T1 is an ICC
      that meets all requirements of factors (1), (2), and (3); T2 meets two of the
      three requirements, T3 meets one of the three requirements and T4 meets none of
      the three requirements. Our data did not support the idea that the hepatoduodenal
      lymph node is regional. The N factors were defined as N0 no lymph node
      metastasis; and N1, positive at any nodes. Thus, the stages of ICC were defined
      as stage I, T1N0M0; stage II, T2N0M0; stage III, T3N0M0; stage IVA, T4N0M0 or any
      TN1M0; and stage IVB, any T any NM1.

PMID- 14598148
TI  - Anterior approach for right hepatectomy for hilar cholangiocarcinoma.
AB  - BACKGROUND/PURPOSE: Right hepatectomy is indicated for hilar cholangiocarcinoma,
      but mobilization of the right lobe could be difficult when perihepatic adhesion
      develops in response to repeated cholangitis and forceful mobilization may
      disseminate bacteria if the obstructed biliary tract contains pus. We encountered
      a patient who died from postoperative sepsis and multiorgan failure. METHODS: To
      circumvent such a difficulty, we employed the anterior approach right hepatectomy
      in a second patient with hilar cholangiocarcinoma. In this patient, liver
      transection and division of the hepatic vein were performed before mobilization
      of the right lobe. RESULTS: The second patient recovered uneventfully.
      CONCLUSION: The anterior approach (utilizing the "no-touch" technique) may be a
      preferred procedure for right hepatectomy for hilar cholangiocarcinoma.

PMID- 14598149
TI  - Hand-assisted laparoscopic left lateral segmentectomy of the liver for
      hepatocellular carcinoma with cirrhosis.
AB  - BACKGROUND/PURPOSE: Despite recent progress in trials with laparoscopic
      hepatectomy, it is still necessary to develop safe and stable techniques. We have
      performed laparoscopic hepatic resection for 30 patients with liver tumors to
      date. We have recently been applying a hand-assisted laparoscopic surgical
      technique for greater safety. METHODS: In the present study, we report techniques
      using a hand-assisted laparoscopic anatomical left-lateral segmentectomy for
      hepatocellular carcinoma with liver cirrhosis. RESULTS: Direct feeling with the
      surgeon's hand makes possible a procedure that is almost identical to open
      surgery in which there is better visualization of the surgical field and
      transected margin, and immediate hemostasis is also achieved by manually
      depressing the bleeding point. CONCLUSIONS: With this method, laparoscopic
      anatomical hepatectomy can be performed more safely for patients with cirrhosis
      than by the fully laparoscopic method, although a larger incision is necessary.

PMID- 14598150
TI  - Management of gallstone ileus.
AB  - BACKGROUND/PURPOSE: Gallstone ileus is an uncommon complication of cholelithiasis
      in the elderly with a high morbidity and mortality rate. This study aims to
      clarify the current surgical management. METHODS: In a retrospective survey over
      the past 11 years there were 9 patients with gallstone ileus, all elderly (mean
      age, 77 years), among 2242 cholecystectomies (0.4%) and 243 operated small
      intestinal obstructions (3.7%). Urgent laparotomy confirmed gallstone obstruction
      and a cholecystoduodenal (89%) or cholecystocolonic (11%) fistula. The operation
      included enterolithotomy alone (3 high-risk cases) or plus fistula repair and
      cholecystectomy (6 cases). There were 3 postoperative complications including
      wound dehiscence, wound infection, and obstructive jaundice (morbidity, 37.5%)
      and 1 death due to myocardial infarction (mortality, 11%). On follow-up (mean, 5
      years), 6 patients with cholecystectomy (in 1 case it was performed 2 months
      after the initial operation) and 1 patient with enterolithotomy alone are well;
      there was 1 death from an unrelated cause after 1 year. CONCLUSION: It seems that
      a one-stage procedure (enterolithotomy plus fistula repair and cholecystectomy),
      when feasible, should be the first choice. Enterolithotomy alone should be
      reserved for only unstable and difficult cases.

PMID- 14598151
TI  - Day-case laparoscopic cholecystectomy: a prospective evaluation of a 6-year
      experience.
AB  - BACKGROUND/PURPOSE: Day-case laparoscopic cholecystectomy (LC) offers convenience
      to patients and cost saving to the healthcare institutes. This article reviews
      our prospectively recorded experience with day-case LC to determine its
      applicability and safety, as well as patient satisfaction. METHODS: Of 744
      consecutive patients who underwent LC over a 6-year period, 140 (19%) were
      scheduled for day-case surgery. Selection criteria included American Society of
      Anesthesiologists (ASA) score of 1 or 2, absence of morbid obesity, low risk for
      common bile duct stones, domicile within 50 km of the hospital, age greater than
      18 and less than 75, and the ability to admit the patient on the day of surgery
      for operation during the morning. Patient satisfaction with day-case surgery was
      assessed by questionnaire at 4-6 weeks after operation. RESULTS: Some 117 of the
      140 patients (84%) were discharged home on the same day of the operation. Two
      patients were re-admitted with abdominal pain, 1 of whom underwent a negative re
      laparoscopy. There were no major complications. The reasons for overnight
      hospital stay were anesthetic in 12 (52%), surgical in 7 (30%), and social or
      logistic in 4 (18%) patients. There were no conversions. The proportion of
      patients scheduled for day-case remained static (median, 18.5%; range, 16%-22%).
      Some 99 of 105 patients (94%) who completed the questionnaire were satisfied with
      day-case surgery. CONCLUSIONS: In carefully selected patients, day-case LC is
      achievable and safe, and provides good patient satisfaction.

PMID- 14598152
TI  - Catalase, superoxide dismutase, and glutathione peroxidase activities in various
      rat tissues after carbon tetrachloride intoxication.
AB  - BACKGROUND: The aim of this study was to determine the possible relationship
      between the activity of three different antioxidant enzymes--peroxidase
      superoxide dismutase, catalase, and glutathione peroxidase--and carbon
      tetrachloride-induced injury. METHODS: Male Wistar rats weighing 200-250 g were
      used in the experiments. Rats of the experimental groups were given carbon
      tetrachloride 0.5 ml/kg i.p. in olive oil (5 mmol/kg body mass) for 1 or 3 days.
      Control group rats were injected with olive oil only for the same period. Brain,
      liver, kidney, and heart supernatants were used for measurement of superoxide
      dismutase (SOD), catalase, and glutathione peroxidase (GPX) activities. RESULTS:
      No statistically significant changes in SOD and GPX activities were observed in
      the liver after CCl4 administration, but catalase activity was significantly
      increased after 24 h and remained at that level during the course of the study.
      In the brain, SOD and catalase activities decreased after 24 h of experiment, but
      GPX activity statistically significantly increased at all time points studied.
      Increased activities of SOD, catalase, and GPX were found in heart after CCl4
      intoxication. The CCl4 injection in our experiment caused a reduction of SOD and
      catalase activities and increased GPX activity in the kidney. CONCLUSIONS: The
      results suggest that change in antioxidant enzyme activities may be relevant to
      the ability of the liver and other investigated organs to cope with oxidative
      stress during CCl4 poisoning.

PMID- 14598154
TI  - Complete remission of disease for 5 years following initial and repeat resection
      of the liver for the removal of 22 metastases of colorectal origin.
AB  - Although liver resection is accepted as the only available treatment that
      regularly produces long-term survival with possible cure in patients with
      colorectal carcinoma metastatic to the liver, controversy appears to exist
      regarding the surgical indication for patients with more than four nodules.
      Similarly, it may be arguable to perform a repeated hepatic resection for a
      patient who developed multiple recurrent liver metastases with a short disease
      free period after the initial liver resection. During the last 7 years, we have
      adopted constantly the aggressive surgical approach to patients with colorectal
      carcinoma metastatic to the liver if the number of tumor nodules identified
      preoperatively were less than ten and irrespective of the length of disease-free
      period after the previous resection. Here we report on a patient who underwent
      hepatic resection twice at an interval of 3 months and in whom a total of 22
      metastatic nodules (6 in the initial hepatic resection and 22 in the repeated
      resection) were removed. The patient is now alive and remains disease-free, 5
      years after the first liver resection.

PMID- 14598153
TI  - Hilar cholangiocarcinoma associated with sarcoid reaction in the regional lymph
      nodes.
AB  - A 74-year-old woman was admitted to our hospital with a 2-week history of
      jaundice. Percutaneous transhepatic cholangioscopy revealed a nodular tumor
      originating in the upper part of the common hepatic duct, which was invading the
      confluence of the right and left hepatic ducts. Microscopic examination of biopsy
      specimens revealed adenocarcinoma. Abdominal ultrasonography and computed
      tomography demonstrated multiple enlarged lymph nodes around the extrahepatic
      bile duct and the common hepatic artery. Laparotomy revealed lymph node
      enlargement in the hepatoduodenal ligament, behind the pancreatic head, and along
      the common hepatic and left gastric arteries. Extended left hepatic lobectomy,
      caudate lobectomy, and resection of extrahepatic bile duct with extended lymph
      node dissection were performed. The histology of permanent specimen revealed no
      tumor metastasis but a sarcoid reaction in the lymph nodes. The patient is in
      good health 21 months after the operation, without any evidence of recurrence.
      This is the first successfully resected case of hilar cholangiocarcinoma
      associated with sarcoid reaction in the regional lymph nodes.

PMID- 14598155
TI  - Surgical approach to tumor recurrence and metastatic lesions of the liver in a
      patient with malignant endocrine tumors of the pancreas: case report.
AB  - We describe herein a 72-year-old woman with tumor recurrence in the residual
      pancreas and metastasis to the liver following a pylorus-preserving
      pancreatoduodenectomy for multiple endocrine tumors in the head of the pancreas.
      Abdominal ultrasonography performed 7 years after the initial surgery detected
      new lesions in the residual pancreas and liver. After recurrence of endocrine
      tumors of the pancreas and metastasis to the liver were diagnosed, the lesions
      were successfully resected by total pancreatectomy with distal gastrectomy and
      both lateral segmentectomy and partial resection of segment 8. Genetic analysis
      using a blood specimen showed that this patient carried the multiple endocrine
      neoplasia type 1 (MEN1) gene mutation. One year after the second resection, the
      patient remains in good health using insulin and has not shown any sign of
      recurrence. This case report describes successful surgical resection for
      recurrence and metastasis of malignant endocrine tumors in a patient with the
      MEN1 gene mutation.

PMID- 14598156
TI  - Biliary and pancreatic drainage after ERCP for choledocholithiasis.

PMID- 14598157
TI  - Insufflation profile and body position influence portal venous blood flow during
      pneumoperitoneum.
AB  - BACKGROUND: We investigated changes in portal venous blood flow (PVBF) during
      carbon dioxide (CO2) pneumoperitoneum to evaluate the effects of different
      insufflation profiles and body positions. METHODS: An established rat model was
      extended by implanting a portal vein flow probe that would enable us to measure
      PVBF for 60 min [t0-t60] in animals subjected to a CO2 pneumoperitoneum with an
      intraabdominal pressure (IAP) of 9 mmHg. Forty-eight male Sprague-Dawley rats
      were randomized into the following four experimental and two control groups:
      decompression group D1 ( n = 8), desufflation for 1 min every 14 min;
      decompression group D2 ( n = 8), desufflation for 5 min, after 27 min; position
      group P1 ( n = 8), 35 degrees head-up position; position group P2 ( n = 8), 35
      degrees head-down position; negative control group C1 ( n = 8), no insufflation;
      positive control group C2 ( n = 8), constant IAP of 9 mmHg for 60 min. RESULTS:
      Pneumoperitoneum and body positions, respectively, reduced PVBF [t1-t60]
      significantly ( p < 0.001) by 32.0% C2, 32.8% D1, 31.1% D2, 40.8% P1, and 48.5%
      P2, as compared to PVBF at t0 in each group. There was a significant difference
      in PVBF reduction between P1 and P2 and also between C2 and both P1 and P2 ( p <
      0.04). CONCLUSIONS: CO2 pneumoperitoneum reduces PVBF significantly (>30%).
      Extreme body positions (35 degrees tilt) significantly intensify PVBF reduction.
      PVBF reduction is significantly more dramatic in subjects placed in a 35 degrees
      head-down position. Short desufflation periods did not improve mean PVBF, but it
      may have beneficial immunological and oncological effects that warrant further
      investigation.

PMID- 14598158
TI  - Laparoscopic distal pancreatectomy for Frantz's tumor in a child.
AB  - Solid pseudopapillary tumor of the pancreas is a rare pathologic entity. Although
      the role of laparoscopy in surgery of the pancreas is still controversial,
      laparoscopic distal pancreatectomy has been reported with good results in adults.
      We report a laparoscopic spleen-preserving distal pancreatectomy in a 9-year-old
      boy who presented with a low-grade malignant tumor. Needle biopsy was impossible.
      A laparoscopic spleen-preserving distal pancreatectomy was performed. We used
      four trocars, and the operative time was 240 min. Conversion to open surgery was
      not necessary. The boy's postoperative recovery was uneventful, and he was
      discharged on the 6th day. CT-scan control at 6 months was normal. This case
      shows that even in advanced surgical cases, such as spleen-preserving distal
      pancreatectomy, laparoscopic procedures can be done safely, within a reasonable
      operative time, in children.

PMID- 14598159
TI  - Hand-assisted laparoscopic resection of serous cystadenoma of the pancreas.
AB  - It is difficult to exclude the possibility of malignancy of pancreatic cystic
      tumors because a biopsy of the pancreas is hard to obtain. The indication of open
      surgery for those cystic tumors without evidence of malignancy is controversial.
      Therefore, laparoscopic or laparoscopically assisted procedure would be an
      adequate choice of treatment for cystic tumors of the pancreas. Hand-assisted
      laparoscopic distal pancreatectomy with preservation of the spleen and the
      splenic artery and vein was performed for two cases of pancreatic cystic tumors.
      Three ports and one hand port were used. After careful dissection and accurate
      hemostasis between the pancreas and splenic vessels, laparoscopic distal
      pancreatectomy was carried out using an endoscopic linear stapler. There were no
      perioperative complications. The pathological diagnoses were oligocystic serous
      cystadenoma and solitary cystic serous cystadenoma, respectively. Hand-assisted,
      spleen-preserving laparoscopic distal pancreatectomy with preservation of the
      splenic artery and vein is a feasible procedure for the treatment of benign or
      borderline-malignant cystic lesions of the distal pancreas.

PMID- 14598160
TI  - Optimization of the microbial synthesis of dihydroxyacetone from glycerol with
      Gluconobacter oxydans.
AB  - An optimized repeated-fed-batch fermentation process for the synthesis of
      dihydroxyacetone (DHA) from glycerol utilizing Gluconobacter oxydans is
      presented. Cleaning, sterilization, and inoculation procedures could be reduced
      significantly compared to the conventional fed-batch process. A stringent
      requirement was that the product concentration was kept below a critical
      threshold level at all times in order to avoid irreversible product inhibition of
      the cells. On the basis of experimentally validated model calculations, a
      threshold value of about 60 kg x m(-3) DHA was obtained. The innovative
      bioreactor system consisted of a stirred tank reactor combined with a packed
      trickle-bed column. In the packed column, active cells could be retained by in
      situ immobilization on a hydrophilized Ralu-ring carrier material. Within 17
      days, the productivity of the process could be increased by 75% to about 2.8 kg x
      m(-3) h(-1). However, it was observed that the maximum achievable productivity
      had not been reached yet.

PMID- 14598161
TI  - Transmitter contents of cells and fibers in the cephalic sensory organs of the
      gastropod mollusc Phestilla sibogae.
AB  - While the central ganglia of gastropod molluscs have been studied extensively,
      relatively little is known about the organization and functions of the peripheral
      nervous system in these animals. In the present study, we used
      immunohistochemical procedures to examine the innervation of the rhinophores,
      oral tentacles and region around the mouth of the aeolid nudibranch, Phestilla
      sibogae. Serotonin-like immunoreactivity was found in an extensive network of
      efferent projections apparently originating from central neurons, but was not
      detected within any peripheral cell bodies. In contrast, large numbers of
      peripheral, and presumably sensory, somata exhibited reactivity to an antibody
      raised against tyrosine hydroxylase (the enzyme catalyzing the initial step in
      the conversion of tyrosine into the catecholamines). Additional tyrosine
      hydroxylase-like immunoreactivity was detected in afferent fibers of the
      peripheral cells and in several cells within the rhinophoral ganglia. The
      presence of serotonin, dopamine and norepinephrine in the rhinophores, tentacles
      and central ganglia was confirmed using high-performance liquid chromatography.
      Finally, FMRFamide-like immunoreactivity was detected in cells and tangles of
      fibers found within the rhinophore, possibly revealing glomerulus-like structures
      along olfactory pathways. FMRFamide-like immunoreactivity was also found in
      somata of the rhinophoral ganglia, in a small number of cells located in the body
      wall lateral to the tentacles and in what appeared to be varicose terminals of
      efferent projections to the periphery. Together, these results indicate several
      new features of the gastropod peripheral nervous system and suggest future
      experiments that will elucidate the function of the novel cells and innervation
      patterns described here.

PMID- 14598162
TI  - Dufour gland of the digger wasp Liris niger: structure and developmental and
      biochemical aspects.
AB  - The tubiform Dufour gland in the digger wasp species Liris niger is about 1.0 mm
      long ( 0.15 mm). An alternating arrangement of longitudinal and circumferential
      bundles of striated muscle fibers surrounds the gland. The Dufour gland, together
      with the venom gland, enters the sting base and terminates in the sting. The
      glandular epithelium is monolayered. Glands about 3 day after imaginal ecdysis
      have an empty lumen but a thick lining epithelium. The gland cells are
      characterized by a well-developed vesicular smooth endoplasmic reticulum, sparse
      rough ER and numerous free ribosomes. They also exhibit several electron-lucent
      vesicles and autophagic vacuoles. Secretion of electron-dense material via the
      gland cuticle into the gland lumen is apparent. Glands more than 20 days after
      imaginal ecdysis display a large lumen and a thin epithelium. The cells show
      signs of degeneration with numerous cytolytic inclusions. Dufour gland liquid
      contains numerous polypeptides of molecular weights ranging from 14 to about 200
      kDa. In addition the secretion consists predominantly of straight-chain
      hydrocarbons, accompanied by small amounts of esters. The major hydrocarbons are
      pentadecane and ( Z)-8-heptadecene. Dufour gland secretion may have several
      functions: (1). the polypeptides might be involved in the gluing process of the
      eggs, while (2). the hydrocarbon oils may function as lubricants for the lancets
      and (3). might soften the secretion, thus allowing easier application of the
      glue. The lipophilic volatile material (4). might also be involved in pheromonal
      signaling.

PMID- 14598163
TI  - Identification of two AGTR2 mutations in male patients with non-syndromic mental
      retardation.
AB  - Mutations in the coding region of the angiotensin II type 2 receptor gene (AGTR2)
      were recently identified to cause X-linked recessive mental retardation. We
      report a mutation screening of the AGTR2 gene in 57 Finnish male patients with
      non-syndromic mental retardation. We identified two mutations, a 62G-->T
      transversion, which leads to a substitution of glycine for valine (G21V) and a
      157A-->T transversion, which causes a substitution of isoleucine for
      phenylalanine (I53F). The patients with AGTR2 sequence variants had
      severe/profound mental retardation, epileptic seizures, restlessness,
      hyperactivity, and disturbed development of speech.

PMID- 14598164
TI  - A deletion mutation in the betaA1/A3 crystallin gene ( CRYBA1/A3) is associated
      with autosomal dominant congenital nuclear cataract in a Chinese family.
AB  - Congenital cataracts are an important cause of blindness worldwide. In a family
      of Chinese descent, a dominant congenital nuclear cataract locus was mapped to
      chromosome 17q11.1-12. The maximum LOD score, 2.49, at recombination fraction 0,
      was obtained for marker D17S1294. The results of both linkage and haplotype
      analyses defined a disease-gene to an 11.78-cM region harboring the gene coding
      for betaA1/A3 crystallin ( CRYBA1/A3). Mutation analysis of the CRYBA1/A3 gene
      identified a 3-bp deletion in exon 4, which cosegregated with the disease risk in
      this family and was not observed in 100 normal chromosomes. This mutation
      resulted in the deletion of a highly conserved glycine at codon 91 (DeltaG91) and
      could be associated with an incorrect folding of betaA1/A3 crystallin. It
      highlights the physiological importance of crystallin and supports the role of
      CRYBA1/A3 in human cataracts formation.

PMID- 14598165
TI  - Evolution and microsynteny of the apyrase gene family in three legume genomes.
AB  - Apyrases have been suggested to play important roles in plant nutrition,
      photomorphogenesis, and nodulation. To help trace the evolution of these genes in
      the legumes--and possibly, the acquisition of new functions for nodulation-
      apyrase-containing BACs were sequenced from three legume genomes. Genomic
      sequences from Medicago truncatula, Glycine max and Lotus japonicus were compared
      to one another and to corresponding regions in Arabidopsis thaliana. A
      phylogenetic analysis of apyrase homologs from these regions and sequences from
      other legume species, as well as other plant families, identified a potentially
      legume-specific clade that contains a well-characterized soybean ( G. soja)
      apyrase, Gs52, as well as homologs from Dolichos, Lotus, Medicago and Pisum.
      Sister clades contain homologs from members of Brassicaceae, Solanaceae, Poaceae
      and Fabaceae. Comparisons of rates of change at synonymous and nonsynonymous
      sites in the Gs52 and sister clades show rapid evolution in the potentially
      legume-specific Gs52 clade. The genomic organization of the apyrase-containing
      BACs shows evidence of gene duplication, genomic rearrangement, and gene
      conversion among Gs52 homologs. Taken together, these results suggest a scenario
      of local apyrase gene duplication in an ancestor of the legumes, followed by
      functional diversification and increased rates of change in the new genes, and
      further duplications in the Galegae (which include the genera Medicago and
      Pisum). The study also provides a detailed comparison of genomic regions between
      two model genomes which are now being sequenced ( M. truncatulaand L. japonicus),
      and a genome from an economically important legume species ( G. max).

PMID- 14598166
TI  - Identification of tissue-embedded ascarid larvae by ribosomal DNA sequencing.
AB  - Polymerase chain reaction (PCR) was applied to identify tissue-embedded ascarid
      nematode larvae. Two sequences of the internal transcribed spacer (ITS) regions
      of ribosomal DNA (rDNA), ITS1 and ITS2, of the ascarid parasites were amplified
      and compared with those of ascarid-nematodes registered in a DNA database
      (GenBank). The ITS sequences of the PCR products obtained from the ascarid
      parasite specimen in our laboratory were compatible with those of registered
      adult Ascaris and Toxocara parasites. PCR amplification of the ITS regions was
      sensitive enough to detect a single larva of Ascaris suum mixed with porcine
      liver tissue. Using this method, ascarid larvae embedded in the liver of a
      naturally infected turkey were identified as Toxocara canis. These results
      suggest that even a single larva embedded in tissues from patients with larva
      migrans could be identified by sequencing the ITS regions.

PMID- 14598167
TI  - Phylogenetic analysis of Theileria species transmitted by Haemaphysalis
      qinghaiensis.
AB  - The phylogenetic relationships between six isolates of Theileria spp. infective
      to small ruminants, and two isolates of Theileria spp. infective to yak, all
      transmitted by Haemaphysalis qinghaiensis, together with the Theileria
      orientalis/sergenti/buffeli group and T. sinensis, were analyzed using the 18S
      ssrRNA gene sequence. The target DNA segment was amplified by polymerase chain
      reaction (PCR). The PCR product was used either for direct sequencing or was
      ligated to the PCR II vector for sequencing. The length of the 18S ssrRNA gene of
      all Theileria spp. involved in this study was around 1,740 bp. Two phylogenetic
      trees were inferred based on the 18S ssrRNA gene sequence of the Chinese isolates
      only, and Chinese isolates and other species of Theileria available in GenBank.
      In the first tree, the Theileria sp. infective to yaks was found to be T.
      sinensis. The Theileria sp. infective to small ruminants was found to be composed
      of two separate species of Theileria. Theileria sp. from Qinghai, Madang,
      Ningxian and Lintan, which was identical to the unidentified Theileria sp.
      described previously, is designated Theileria sp (China 1). The Theileria sp.
      from Longde, Zhangjiachuan and Lintan, which has not been described previously,
      is designated Theileria sp. (China 2) in order to avoid confusion. In the second
      tree, Theileria sp. (China 1) was closely related to benign Theileria, such as T.
      buffeli and T. sergenti, while Theileria sp. (China 2) was separated from other
      Theileria spp. The results indicate that H. qinghaiensis transmit at least three
      species of Theileria, two which are infective to sheep and goats, but not yak and
      one which is infective to yaks and cattle, but not to sheep and goats.

PMID- 14598168
TI  - Immunoblot analysis of Trichomonas vaginalis antigens recognized by rabbit
      hyperimmune serum raised against exoantignes.
AB  - The SDS-PAGE and immunoblot were used to identify Trichomonas vaginalis antigenic
      epitopes present in purified somatic and exo-antigens. The presence of common
      immunogenic proteins corresponding to molecular weights of 76, 60 and 23 kDa was
      revealed. Distinctive immunogenic bands of 92, 72, 55 and 40 kDa for the exo
      antigens, and of 110, 80, 78 and 50 kDa for the somatic antigens, appeared when
      the antigens were probed by the homologous immune rabbit serum.

PMID- 14598169
TI  - Polymerase chain reaction-based genotype classification among human Blastocystis
      hominis populations isolated from different countries.
AB  - Since the genotype of human Blastocystis hominis isolates is highly polymorphic,
      PCR-based genotype classification using known sequenced-tagged site (STS) primers
      would allow the identification or classification of different genotypes. Five
      populations of human B. hominis isolates obtained from Japan, Pakistan,
      Bangladesh, Germany, and Thailand were subjected to genotype analysis by using
      seven kinds of STS primers. Ninety-nine out of 102 isolates were identified as
      one of the known genotypes, while one isolate from Thailand showed two distinct
      genotypes and two isolates from Japan were negative with all the STS primers. The
      most dominant genotype among four populations, except for all four isolates from
      Thailand, was subtype 3 and it varied from 41.7% to 92.3%. The second most common
      genotype among four populations was either subtype 1 (7.7-25.0%) or subtype 4
      (10.0-22.9%). Subtype 2, subtype 5, and/or subtype 7 were only rarely detected
      among the isolates from Japan and Germany, while subtype 6 was not detected. The
      phylogenetic position of the two isolates which were negative with all STS
      primers, was inferred from the small subunit rRNA (SSU rRNA) genes with the known
      sequence data of 20 Blastocystis isolates. Since the two isolates were positioned
      in an additional clade in the phylogenetic tree, this suggested they were a new
      genotype. These results demonstrated that PCR-based genotype classification is a
      powerful tool with which to analyse genotypes of Blastocystis isolates obtained
      from clinical samples. In addition, two groups of the isolates from 15
      symptomatic and 11 asymptomatic patients in Bangladesh were compared with the PCR
      based subtype classification. Since both groups were only classified into two
      distinct genotypes of subtype 1 or subtype 3 and no statistically significant
      difference was observed between the two groups, in this study it could not be
      shown that the specific genotype correlated with the pathogenic potential of B.
      hominis.

PMID- 14598170
TI  - Functional characterization of an alternative [lactate dehydrogenase-like] malate
      dehydrogenase in Plasmodium falciparum.
AB  - The catalysis of malate dehydrogenase (MDH) in Plasmodium falciparum (pfMDH)
      which involves NAD/NADH coupling is crucial for the parasite's pathogenicity.
      Primers were designed based on the P. falciparum genome resource, and these
      facilitated the cloning of a gene coding for pfMDH from a local clinical isolate.
      The DNA sequence of the cloned gene revealed an open-reading frame that encodes a
      protein of 313 amino acids. After induction in Escherichia coli BL21, enzyme
      assays of the expressed pfMDH purified by affinity chromatography exhibited
      significant enzyme activity of about 50 U/mg, where one unit (U) of enzyme
      activity is defined as the amount of enzyme oxidising 1 microol NADH/min. Based
      on its phylogenetic status amongst MDHs and lactate dehydrogenases (LDHs), the
      cloned gene was clearly defined as belonging to the NADH-dependent [LDH-like]
      MDHs. It is noteworthy that pfMDH harbours unique structural characteristics
      potentially useful for screening drugs specific for disabling parasitic enzymes.

PMID- 14598171
TI  - Infection of snails with bird schistosomes and the threat of swimmer's itch in
      selected Polish lakes.
AB  - Studies of selected species of Lymnaeidae and Planorbidae showed that infection
      with bird schistosomes occurred in 14 of the 26 Polish lakes studied. In
      Planorbarius corneus larvae of Bilharziella polonica were found, and in Lymnaea
      stagnalis and Radix auricularia larvae of Trichobilharzia ocellata. In spite of
      their comparatively low prevalence, cercariae, potentially pathogenic to humans,
      may have caused dermatitis in patients registered in one of the regions under
      study. The low prevalence of infection among the host snails may have been
      compensated for by the enormous number of cercariae released by them, which,
      moreover, showed a long-lasting viability, particularly at low ambient
      temperature.

PMID- 14598172
TI  - The mitochondrial transporter family (SLC25): physiological and pathological
      implications.
AB  - The mitochondrial carriers (MCs) shuttle a variety of metabolites across the
      inner mitochondrial membrane (i.m.m.). In man they are encoded by the SLC25
      genes. Some MCs have isoforms encoded by different SLC25 genes, whereas the
      phosphate carrier has two variants arising from an alternative splicing of
      SLC25A3. Six MCs have been sequenced after purification, and many more have been
      identified from their transport and kinetic properties following heterologous
      over-expression and reconstitution into liposomes. All MCs of known function
      belong to the same protein family, since their polypeptide chains consist of
      three tandemly related sequences of about 100 amino acids, and the repeats of the
      different carriers are homologous. They probably function as homodimers, each
      monomer being folded in the membrane into six transmembrane segments. The
      functional information obtained in studies with mitochondria and/or the
      reconstituted system has helped to gain an insight into the physiological role of
      the MCs in cell metabolism, as have tissue distribution, the use of knock-out
      mice (and/or yeast) and over-expression in human cell lines (or yeast) of
      individual carriers and isoforms. At the same time, the cloning and functional
      identification of many SLC25 genes has made it possible (i) to identify the genes
      (and their defects) responsible for some diseases, e.g. Stanley syndrome and
      Amish microcephaly, and (ii) where the genes were already known, to characterize
      the function of the gene products and hence understand the molecular basis and
      the symptoms of the diseases, e.g. hyperornithinaemia, hyperammonaemia and
      homocitrullinuria (HHH) syndrome and type II citrullinemia. It is likely that
      further extension and functional characterization of the SLC25 gene family will
      elucidate other diseases caused by MC deficiency.

PMID- 14598173
TI  - Open-surgery management of morbid obesity: old experience-new techniques.
AB  - Bariatric surgery is well established to treat morbidly obese patients (BMI >40
      kg/m(2)) with various techniques. Gastric-restriction procedures [adjustable
      gastric band, vertical banded gastroplasty (VBG)] reduce caloric intake and are
      well accepted (weight loss up to BMI 28-33 kg/m(2) after 5 years), but they are
      less effective in super-obese patients and in sweet-eaters. For that group
      combined techniques, such as duodenal switch, gastric bypass or bilio-pancreatic
      diversion, could produce a better weight loss (between 60 and 160 kg or BMI of 25
      30 kg/m(2)) with acceptable long-term side effect; however, due to malabsorption,
      a lack of minerals and vitamins, even protein, could occur and have dangerous
      side effects. Both basic techniques have their place in the treatment of morbid
      obesity. The surgical approach-open or mini-invasive-is only of minor importance.
      Technical complications should be avoided, especially band dislocation (2-12%) or
      suture leak. Long-term follow-up is very important because obesity is a chronic
      disease with a high risk of recurrence, even after bariatric surgery.

PMID- 14598174
TI  - Toluene exposure below 50 ppm and cognitive function: a follow-up study with four
      repeated measurements in rotogravure printing plants.
AB  - OBJECTIVE: There are findings of cross-sectional studies on slight cognitive
      effects due to toluene exposure below 50 ppm. The critical points of the earlier
      studies will be scrutinised by a follow-up study with four examinations in 5
      years. METHODS: Employees from 14 magazine rotary printing plants were classified
      into groups of "high" (printing area) vs "low" (end-processing) and "short" vs
      "long" exposure. The sample size of 333 in examination 1 decreased to 216 in
      examination 4. A repeated-measurement design could be applied for 192 persons.
      Current exposure was measured by personal air sampling (n=2,521). Data for past
      exposure (lifetime weighted average exposure, LWAE) were based on job exposure
      matrices. High-exposure and low-exposure groups were characterised by 26 ppm vs 3
      ppm (current exposure) and 45 ppm vs 9 ppm (LWAE). For long-exposure and short
      exposure groups 21 vs 6 years were ascertained. Attention (symbol digit
      substitution, switching attention, simple reaction), memory (digit span forward
      and backwards, immediate and delayed reproduction of pictures), and psychomotor
      functions (steadiness, line tracing, aiming, tapping, peg board) were measured as
      dependent variables. RESULTS: Separate stepwise regressions for examinations 1 to
      4, which included the co-variables age, level of education, carbohydrate
      deficient transferrin as an alcohol marker, and trait anxiety as personality
      characteristic, did not exhibit remarkable exposure impacts on the performance
      variables. Repeated-measures analyses of covariance, which included all
      examination periods, also did not exhibit significant impacts of LWAE or current
      exposure on the functions measured. Age and education were the dominant factors
      for the variability of the data. Additionally, carbohydrate-deficient transferrin
      and trait anxiety showed sporadic impacts on the test results. CONCLUSION:
      Evidence for psychological performance effects due to long-term toluene exposure
      below 50 ppm could not be proved.

PMID- 14598176
TI  - Development of a new method and device for securing haemostasis during transoral
      surgery: in vitro and cadaver experiments.
AB  - The objective of this study is to present cadaver and model experiments of an
      instrument and technique that may overcome the problems of achieving hemostasis
      after tonsillectomy and surgery of the tongue base. The safety and the reduced
      need for microclips in surgeries in these areas can be accomplished by
      introducing the "ligature" device, which makes it possible to pass a suture under
      a blood vessel or other diffuse areas of bleeding with a single movement. This
      technique may also be applied to operations on the supraglottic larynx,
      oropharynx and hypopharynx. Utilization in the larynx may be more limited. This
      new instrument and technique for the ligature device has the potential to be
      applied successfully in other fields of surgery. The main advantages of this
      technique are its simplicity and safety.

PMID- 14598175
TI  - Expression of stabilin-2, a novel fasciclin-like hyaluronan receptor protein, in
      murine sinusoidal endothelia, avascular tissues, and at solid/liquid interfaces.
AB  - Stabilin-2, the hepatic hyaluronan receptor, has recently been cloned by us.
      Together with stabilin-1, stabilin-2 constitutes a novel family of fasciclin-like
      hyaluronan receptor homologues. Here, we analyzed expression of stabilin-2 (mStab
      2) in a broad array of C57BL/6 mouse organs and tissues. While northern blot
      analysis showed positive expression of mStab-2 mRNA confined to liver and spleen,
      immunohistochemistry demonstrated mStab-2 protein expression in the endothelial
      sinuses of liver, lymph nodes, spleen, and bone marrow, and in specialized
      structures of eye, heart, brain, and kidney. Expression of mStab-2 was detected
      in corneal and lens epithelium, in mesenchymal cells of the heart valves, in the
      ependymal cells lining the ventricles in the brain, and in the prismatic
      epithelial cells covering the renal papillae. In pathological conditions, such as
      tumor growth or wound healing processes, mStab-2 was not expressed in the newly
      formed vasculature or other tissue components. Based on these results, we suggest
      that mStab-2 might be involved in the clearance of hyaluronan from the lymph or
      the blood circulation via the network of endothelial sinuses. At the other mStab
      2-positive tissues sites that are either avascular and/or demarcate a
      solid/liquid interface, mStab-2 may serve to maintain tissue integrity by
      supporting extracellular matrix turnover or it may contribute to maintaining
      fluidity of bodily liquids by resorption of hyaluronan.

PMID- 14598177
TI  - Apoptosis and p63 expression in the pathogenesis of bullous lesions of endemic
      pemphigus foliaceus.

PMID- 14598178
TI  - The effect of temperature on digestive and assimilation efficiency, gut passage
      time and appetite in an ambush foraging lizard, Cordylus melanotus melanotus.
AB  - In ectotherms, an increase in body temperature increases metabolic rate and may
      increase rates of digestive processes. We measured the thermal dependence of the
      apparent digestive and apparent assimilation efficiencies (ADE and AAE), gut
      passage time (GP) and appetite in Cordylus melanotus melanotus, a medium sized
      Crag Lizard, which is endemic to South Africa. Trials were conducted at 20, 22,
      25, 30, 32 and 35 degrees C under controlled conditions. Trials lasted 14 days,
      during which, lizards were fed ca. 1 g mealworms per day. Glass beads were used
      as markers to determine GP at the beginning and end of trials. Faeces and urates
      were collected daily and oven dried at 50 degrees C. The energy content of
      egested matter was then measured using bomb calorimetry. ADE and AAE were not
      affected by temperature for either males or females. The mean+/-SE ADE and AAE
      were 94.4+/-0.3% and 87.2+/-0.6%, respectively. GP was not significantly
      different between males and females at any temperature, but decreased
      significantly with increasing temperature. Appetite was significantly different
      between the different temperatures measured. The decrease of gut passage time
      with increasing temperature was expected, since the digestive and assimilation
      efficiencies are similar over the range of temperatures tested. Lizards are thus
      assimilating a similar proportion of ingested energy, but at faster rates at
      higher temperatures. The results indicate that the digestive physiology of this
      species results in maximum energy gain per meal in environments where food is
      scarce.

PMID- 14598179
TI  - Expression of matrix metalloproteinases in vasculitic neuropathy.
AB  - The aim of this study was to investigate the expression pattern and cellular
      source of matrix metalloproteinases (MMP) in vasculitic neuropathy. Matrix
      metalloproteinases are endopeptidases degrading components of extracellular
      matrix proteins, and they have been implicated in the pathogenesis of
      inflammatory demyelination. They are induced by cytokines, secreted by
      inflammatory cells, and enhance T cell migration. Vasculitic neuropathy occurs as
      a component of systemic vasculitis or as an isolated angiitis of the peripheral
      nervous system, and T cell-mediated inflammation is detected in its pathogenesis.
      Nerve biopsy sections of eight patients with nonsystemic vasculitic neuropathy
      (NSVN) and four with systemic vasculitic neuropathy were examined for the
      presence of CD4+, CD8+, and CD68+ cells and immunohistochemically for MMP-2 and
      MMP-9 expression. Nerve biopsies of eight patients with noninflammatory
      neuropathy were used as a control group. Semiquantitative polymerase chain
      reaction analysis was performed to detect MMP-2 and MMP-9 mRNA. The predominant
      cells were CD8+ and CD68+ T cells. Expression of MMP-9, but not MMP-2, was
      increased in perivascular inflammatory infiltrate in nerve tissues of vasculitic
      neuropathy patients. This MMP-9 expression correlated positively with
      immunostaining of CD8+ T cells. No difference was detected between immunostaining
      patterns of nonsystemic and systemic vasculitic neuropathies with the antibodies
      used, except in MMP-9 immunostaining, which was found to be enhanced in NSVN
      group. Polymerase chain reaction analysis revealed elevated mRNA levels of MMP-9
      and MMP-2 compared with controls, but this did not reach statistical
      significance. Our results imply a pathogenic role for MMP-9 secreted from CD8+
      cells in vasculitic neuropathy.

PMID- 14598180
TI  - Tuberculous sacroiliitis: a case report.
AB  - Tuberculosis can affect sacroiliac joints, but only a few such cases have been
      reported. The onset is usually insidious, and early diagnosis requires a high
      index of clinical suspicion. We report herein a culture-proven case of
      tuberculous sacroiliitis which initially mimicked neoplastic infiltration on CT
      scan.

PMID- 14598182
TI  - Immune hemolysis-serological and clinical aspects.
AB  - The differential diagnosis of anemia must consider immune hemolytic anemias as a
      frequent cause. Whereas detection of anti-red blood cell (RBC) alloantibodies
      frequently induced by immunogenic stimuli (transfusion, pregnancy) is performed
      by routine serology, diagnosing autoimmune hemolytic anemias or drug-induced
      hemolytic anemias remains a challenge, usually requiring close collaboration of a
      number of disciplines. Positive direct antiglobulin test (Coombs' test)
      represents a central criterion in diagnosing immune hemolytic anemias, leading to
      further detailed analyses. The most-severe type of immune-mediated hemolysis is
      acute intravascular hemolysis after ABO incompatible RBC transfusion. This review
      highlights underlying biochemical aspects, immunohematological diagnostics, and
      the clinical relevance of RBC allo- and autoantibodies, including paroxysmal
      nocturnal hemoglobinemia and drug-induced hemolysis. Finally, current and partly
      experimental therapeutic strategies of immune hemolytic anemias are summarized.

PMID- 14598183
TI  - Idiopathic pulmonary fibrosis/cryptogenic fibrosing alveolitis.
AB  - Idiopathic pulmonary fibrosis (IPF), synonymous with cryptogenic fibrosing
      alveolitis (CFA), is a progressive and usually fatal disease of unknown cause
      characterized by sequential acute lung injury with subsequent scarring and end
      stage lung disease. Historically, IPF/CFA encompassed a heterogeneous group of
      different histological and clinical entities arising in an idiopathic setting.
      Recently, the American Thoracic Society (ATS) and European Respiratory Society
      (ERS) core committee has redefined diagnostic criteria for both IPF/CFAand
      idiopathic interstitial pneumonias confining the term IPF/CFA to patients with a
      histological pattern of usual interstitial pneumonia on lung biopsy. This review
      attempts to refine the clinico-radiological-pathological features that together
      define IPF/CFA as it is understood today, and to summarize the rationale of new
      therapeutic approaches based on the current understanding of the pathogenetic
      mechanisms.

PMID- 14598184
TI  - Immunopathogenesis of toxoplasmosis.
AB  - Toxoplasmosis is a ubiquitous infection affecting 500 million persons around the
      world, with a range of incidence 12%-90%, increasing with age, education,
      crowding and sanitary habits. Cats are the definitive host. Infection is
      primarily congenital but acquired ocular infection has been documented. The
      review focuses on the immunopathogenesis of toxoplasmosis with emphasis on the
      eye problem due to its morbidity. The response to infection correlates with both
      parasitic and retinal antigens. The clinical picture and histopathology is a
      reflection of the immune response which constitutes early humeral response which
      presents both systemically and locally primary infection and is elevated with
      reactivation. This is followed by the cellular response, varying from low grade
      monocular infilterate a total tissue destruction with response of live parasites
      especially in immuno-compromised patients. Penetration of the parasite and its
      enclosure within the parasitophorous vacuole and its eneyst all make its
      eradicatier impossible. This reflects the variability of antiparasitic therapy
      that include folate antagonists, macrolides, hydroxy naphthoquindones and
      fluoroquinolones. Use of corticosteroid should be limited to severe reactions and
      should be associated with specific therapy.

PMID- 14598185
TI  - Defective expression of FasL and Bax in human lung cancer.
AB  - The present studies investigated whether FasL and Bax genes are expressed in
      pleuro-pulmonary biopsies from patients with lung cancer. FasL, Bax, and TNFalpha
      mRNAs were detected in 19 biopsies of primary or metastasic lung cancer by
      fluorescent in situ hybridization assays. Fluorescent probes were produced by
      polymerase chain reaction using a human spleen lambda gt11 library and specific
      primers for FasL, Bax, and TNFalpha. Proteins were detected by
      immunohistochemistry using monoclonal anti- FasL, anti-Bax, and anti-TNFalpha
      antibodies. Chromatin fragmentation was detected by TUNEL. Seven negative samples
      from subjects without lung pathology were obtained during legal autopsies and 12
      positive control biopsies from patients with lung infections were also included.
      Sixty-eight percent of lung cancer biopsies exhibited FasL; Bax was expressed in
      68% and TNFalpha in 63%. FasL protein was detected in 21%, Bax protein in 26%,
      and TNFalpha was present in 31% of cancer biopsies. A low degree of apoptosis in
      lung cancer was demonstrated by TUNEL assays. A defect in FasL, Bax, and TNFalpha
      gene expression was found in lung cancer biopsies. Some tumors normally expressed
      the mRNA of FasL, Bax, or TNFalpha, but their proteins were absent, or were non
      functional, since TUNEL assays were negative. Such a failure would contribute to
      cancer cell survival and dissemination.

PMID- 14598186
TI  - Prognostic significance of HLA-DR antigen in serous ovarian tumors.
AB  - The antigens encoded by the major histocompability complex (HLA-DR) are cell
      glycoproteins that play a fundamental role in the regulation of the immune
      response. The prognosis of ovarian cancer is dependent on the histological type
      and on the clinical stage at diagnosis. Our study reports the value of HLA-DR
      antigen as a prognostic marker of ovarian serous adenocarcinoma. We studied 31
      cases of serous ovarian cystadenoma, 12 cases of serous ovarian borderline
      cystadenoma, and 39 cases of well-differentiated cystadenocarcinoma for HLA-DR
      monoclonal antigen. We also studied the T helper marker (CD4) in the tumor stroma
      of the relevant cases, given that it is now known that the dependence of immune
      responsiveness on the class II antigens reflects the central role of these
      molecules in presenting antigen to T helper cells. HLA-DR was expressed in 20 of
      31 cystadenomas (64.5%), 4 of 12 borderline tumors (33.3%), and in 10 of 39
      invasive carcinomas (25.6%). CD4 was expressed in 9 of 31 cystadenomas (29%), 5
      of 12 borderline tumors (42%), and in 26 of 39 invasive carcinomas (67%). There
      was a statistically significant difference for the two examined antigens in
      cystadenomas ( p<0.001) and invasive carcinomas ( p<0.001), whereas there was no
      statistical difference in borderline tumors ( p<0.5). The results showed
      decreased expression of HLA-DR and increased expression of CD4 as the lesion
      progressed to malignancy. The aberrant expression of HLA-DR by epithelial cells
      of cystadenomas, of borderline tumors, and of invasive adenocarcinomas agrees
      with the hypothesis of the adenoma/adenocarcinoma sequence. The immune attraction
      mechanism by low HLADR signaling seems to be of minor importance in the malignant
      and metastatic potential of serous ovarian tumors.

PMID- 14598187
TI  - Serum CA 19-9 levels as a diagnostic marker in cystic fibrosis patients with
      borderline sweat tests.
AB  - Patients with normal or borderline sweat tests present a diagnostic challenge. In
      spite of the availability of genetic analysis and measurement of nasal potential
      difference, there is still uncertainty in diagnosing cystic fibrosis in some
      patients. CA 19-9 is a tumor-associated antigen whose levels were previously
      found to be elevated in some cystic fibrosis patients. We investigated whether
      serum CA 19-9 levels can contribute to establishing the diagnosis of cystic
      fibrosis in patients with a borderline sweat test, and evaluated the influence of
      different clinical variables on CA 19-9 levels. Serum CA 19-9 levels were
      measured in 82 cystic fibrosis patients grouped according to their genotype and
      in 38 healthy individuals. Group A included 50 patients who carried two mutations
      previously found to be associated with a pathological sweat test and pancreatic
      insufficiency (DeltaF508, W1282X, G542X, N1303K, and S549R). Group B included 13
      compound heterozygote cystic fibrosis patients who carried one mutation known to
      cause mild disease with a borderline or normal sweat test and pancreatic
      sufficiency (3849+10kb C-->T, 5T). Group C included 38 normal controls. Nineteen
      cystic fibrosis patients carried at least one unidentified mutation. An
      association between CA 19-9 levels and age, pulmonary function, pancreatic
      status, sweat chloride, previous pancreatitis, serum lipase, meconium ileus,
      distal intestinal obstruction, liver disease, and diabetes was investigated. The
      distribution of CA 19-9 levels was significantly different between the three
      groups ( p<0.01); high CA 19-9 levels were found in 60% (30/50) of group
      Apatients and in 46.6% (6/13) of group B patients, but in only 5.2% (2/38) of the
      controls. CA 19-9 levels were inversely related to forced expiratory volume in 1
      s, while no association was found with the other clinical parameters examined.
      Our findings suggest that the serum CA 19-9 in cystic fibrosis patients
      originates in the respiratory system, and has a useful ancillary role,
      particularly when diagnostic uncertainty exists. Hence, the diagnosis of cystic
      fibrosis should be considered in patients with borderline sweat tests and high CA
      19-9 levels, but normal levels do not exclude cystic fibrosis.

PMID- 14598188
TI  - Endotoxinemia in the portal and the systemic circulation in obstructive jaundice.
AB  - Endotoxinemia in patients with obstructive jaundice is linked to acute renal
      failure and sepsis and remains a major cause of complications during
      postoperative treatment. The current study examines the mechanisms of
      endotoxinemia in the portal and the systemic circulation in obstructive jaundice.
      As an experimental model of the disease we used rabbits subjected to sham
      operation. Serum total bilirubin aminotransferases and endotoxin concentrations
      were determined at 2, 5, 8, and 13 days after operation. Endotoxin concentrations
      were estimated by the limulus lysate endotoxin test. A high frequency of portal
      or systemic endotoxinemia is observed in obstructive jaundice, but no difference
      between endotoxinemia levels in the portal and systemic circulation was observed.

PMID- 14598189
TI  - Heredity and pituitary response to exercise-related stress in trained men.
AB  - To evaluate the role of heredity in the pituitary responses to exercise-related
      stress, serum ACTH, beta-endorphin, cortisol, GH, and PRL responses to a thirty
      minute treadmill exercise at individual anaerobic threshold were evaluated in
      nine pairs of male monozygotic twin athletes. Hormone evaluations were performed
      before (-30, -15, 0 pre) and after exercise (0 post, + 15, + 30, + 45, + 60, and
      + 90 min). The intraclass correlation coefficient (expression of within-pair
      resemblance) was computed for each hormone before and after exercise as area
      under curves (AUC), absolute values, and percentage of variation, respectively.
      The exercise-related stress condition induced a significant increase for all
      evaluated hormones before (anticipatory response) and/or after exercise. As new
      data, we observed: 1) A significant within-pair resemblance for exercise-related
      GH and PRL increase (AUCs and/or absolute values), and for the percentage of
      variation of cortisol, and 2) the lack of significant resemblance for the
      observed increase of ACTH, cortisol and absolute beta-endorphin serum
      concentration. This first co-twin control study supports the hypothesis that, in
      trained men, there are probably different relative roles for the influence of
      genetic factors on the pituitary hormones involved in physiological adaptation to
      exercise-related stress. Furthermore, our findings justify further investigations
      into this topic.

PMID- 14598190
TI  - Gender influence on the oxygen consumption of the respiratory muscles in young
      and older healthy individuals.
AB  - To understand the influence of gender on oxygen consumption of respiratory
      muscles (VO(2)resp), 32 healthy subjects participated in the study (16 males, 16
      females). They were divided into four groups: young males, young females, older
      males and older females. We used a closed circuit device which allowed a
      continuous increase in external dead space at a constant rate of 300 ml per 90 s
      and was equipped with a 9-L Gould spirometer filled with 100 % O(2). As log
      VO(2)tot (total body O(2) consumption) was linearly related to VE, we calculated
      the slope value (log VO(2)tot/VE) and the Y-intercept (VE = 0) of the semilog
      regression, representing the increase of VO(2)resp and log VO(2)met (metabolic
      O(2) consumption). The main results showed that the mean of the individual slope
      Delta(logVO(2)tot/VE) was steeper in the females than in the males in young and
      also in older subjects. In addition, VO(2)met in young and older females was
      lower compared with that in age-matched males. Therefore, we conclude that the
      oxygen cost of breathing was higher in females versus males subjects.

PMID- 14598191
TI  - The prevalence of doping in Flanders in comparison to the prevalence of doping in
      international sports.
AB  - For many years, doping has been considered a major problem in sports. Recent
      doping cases have shocked the general public and press reports have further
      generated the idea that a great number of athletes are doped. In this study
      statistical data provided by the International Olympic Committee (1996 - 2000) to
      IOC accredited laboratories and results from the Flemish anti-doping program
      (1993 - 2000) are discussed. During these periods, the average percentage
      positive samples in the IOC accredited laboratories and in Flanders were 1.8 %
      and 4.1 %, respectively. The percentage of positive samples was significantly
      higher for in-competition than for out-of-competition samples. During the period
      1993 - 2000, doping was detected in all sports in Flanders, for which a
      representative number of samples (n > 50) was tested except mini-soccer, where no
      positive doping samples were found. The use of doping among male athletes is
      significantly higher than for female athletes. Bodybuilding and power lifting had
      the highest incidence of positive cases in Flanders. The distribution of detected
      drugs among the different groups of prohibited substances shows a significant
      increase in the number of samples containing cannabis over the last years. The
      occurrence of cannabis in all sports and the high frequency of detection in
      Flanders, indicate that cannabis is predominantly misused as a "social" drug
      rather than for doping purposes. In Flanders, multiple prohibited substances were
      detected in 41 % of all positive cases. At least 27.6 % out of those were due to
      co-administration of drugs.

PMID- 14598193
TI  - Time limit and VO2 slow component at intensities corresponding to VO2max in
      swimmers.
AB  - The purpose of this study was to measure, in swimming pool conditions and with
      high level swimmers, the time to exhaustion at the minimum velocity that elicits
      maximal oxygen consumption (TLim at vVO(2)max), and the corresponding VO(2) slow
      component (O(2)SC). The vVO(2)max was determined through an intermittent
      incremental test (n = 15). Forty-eight hours later, TLim was assessed using an
      all-out swim at vVO(2)max until exhaustion. VO(2) was measured through direct
      oximetry and the swimming velocity was controlled using a visual light-pacer.
      Blood lactate concentrations and heart rate values were also measured. Mean
      VO(2)max for the incremental test was 5.09 +/- 0.53 l/min and the corresponding
      vVO(2)max was 1.46 +/- 0.06 m/s. Mean TLim value was 260.20 +/- 60.73 s and it
      was inversely correlated with the velocity of anaerobic threshold (r = -0.54, p <
      0.05). This fact, associated with the inverse relationship between TLim and
      vVO(2)max (r = -0.47, but only for p < 0.10), suggested that swimmers' lower
      level aerobic metabolic rate might be associated with a larger capacity to
      sustain that exercise intensity. O(2)SC reached 274.11 +/- 152.83 l/min and was
      correlated with TLim (r = 0.54), increased ventilation in TLim test (r = 0.52)
      and energy cost of the respiratory muscles (r = 0.51), for p < 0.05. These data
      suggest that O(2)SC was also observed in the swimming pool, in high level
      swimmers performing at vVO(2)max, and that higher TLim seems to correspond to
      higher expected O(2)SC amplitude. These findings seem to bring new data with
      application in middle distance swimming.

PMID- 14598192
TI  - Physical and physiological factors associated with success in professional alpine
      skiing.
AB  - Scientific data on the physiological profile of world class skiers are sparse.
      During the last decade the Austria Ski Team was the most successful in the world.
      It was the objective of this study to describe the physical and physiological
      characteristics of World Cup (WC) skiers. Twenty female and 28 male members of
      the Austrian WC Ski Team were examined pre- and post-seasonally from 1997 to
      2000. Physical parameters such as age, height, body mass, body mass index,
      percent body fat and thigh circumference were recorded from each athlete. The
      physiological variables investigated consisted in the aerobic power and in the
      muscle strength of the lower limbs. Racing performance was defined by the WC
      ranking position. The athlete's aerobic performance capacity was assessed by
      maximal exercise testing on a bicycle ergometer, and the isokinetic muscle
      strength of the knee extensor and flexor muscles by the use of a computer
      interfaced dynamometer. From 1997 to 2000 about half (48 %; n = 106) of all
      alpine WC racing events (n = 221) were won by the athletes investigated. The
      typical world class skier is in the mid-twenties (25.2 y [female]; 27.6 y
      [male]). The mean values for height were 1.66 m (female) vs. 1.81 m (male), for
      body mass 65.1 kg (female) vs. 87 kg (male) and for the percentage of body fat
      24.5 % (female) vs. 15.8 % (male). The maximum power output was 4.3 +/- 0.4
      (female ) and 4.7 +/- 0.4 W/kg (male), the corresponding values for VO(2)max were
      55 +/- 3.5 (female) and 60 +/- 4.7 ml/kg/min (male). The maximal values for peak
      torque and work for knee extension amounted to 206 +/- 21 (female) and 334 +/- 43
      Nm (male), and 2690 +/- 364 (female) and 4414 +/- 629 J (male), respectively. In
      both sexes there were neither significant laterality nor dysbalance. The
      hamstring/quadriceps ratios were between 0.57 - 0.60. Among all physical and
      physiological variables, only the aerobic power in males was found to be strongly
      correlated (r = 0.947; p = 0.001 for W (max); r = 0.964; p < 0.001 for VO(2)max)
      to racing performance. The study proves the practical experience that success in
      professional alpine skiing is not related to single physiological variables. Two
      main factors, however, are crucial, i. e. high levels of aerobic power and muscle
      strength.

PMID- 14598194
TI  - Maximal lactate steady state does not correspond to a complete physiological
      steady state.
AB  - The purpose of this study was to verify whether the maximal lactate steady state
      (MLSS) corresponds to a physiological steady state. Eight male trained subjects
      performed a 30-min test on a cycle ergometer at a constant power corresponding to
      their own MLSS which had been previously determined. No significant variation was
      observed between the 10th and the 30th min for arterial lactate concentration,
      redox state, arterial oxygen pressure, arterial oxygen saturation, bicarbonates
      concentration, base excess, hematocrit, hemoglobin concentration, plasma volume,
      oxygen uptake, carbon dioxide output, gas exchange ratio, minute ventilation,
      ventilatory equivalents for oxygen and carbon dioxide, and arterial systolic
      blood pressure values. However, arterial carbon dioxide pressure and pH values
      were significantly different between the 10th and the 30th min (p < 0.01).
      Respiratory rate values and heart rate significantly increased (p < 0.01). These
      results indicate that MLSS does not correspond to a complete physiological steady
      state.

PMID- 14598195
TI  - Effects of body mass index on the accuracy of an electronic pedometer.
AB  - Electronic pedometers are accurate for assessing steps taken while walking in
      normal weight adults but the accuracy of these devices has not been tested in
      overweight and obese men and women. The primary purpose of this study was to
      assess the accuracy of an electronic pedometer for measuring steps taken at
      various walking speeds in groups of adults with variations in body mass index
      (BMI). The secondary purpose was to determine if the manufacturer recommended
      position is the best placement position for overweight and obese adults.
      Participants were categorized into one of three BMI categories identified by the
      World Health Organization: normal (N = 25; < 25 kg x m(-2)), overweight (N = 24;
      25 - 29.9 kg x m(-2)), or obese (N = 17; > or = 30 kg x m(-2)). Participants
      walked on a treadmill for 3 min at 54, 67, 80, 94, and 107 m x min(-1) for a
      total of 15 min. During the treadmill walking, three electronic pedometers
      tallied steps taken. The pedometers were placed at the waist level, one on the
      anterior mid-line of the thigh (front; manufacturer recommended placement), one
      on the mid-axillary line (side), and one on the posterior mid-line of the thigh
      (back). Concurrently, a researcher counted steps using a hand-tally counter.
      Category of BMI did not affect the accuracy of the pedometer at any walking speed
      (54 m x min(-1), p = 0.991; 67 m x min(-1), p = 0.556; 80 m x min(-1), p = 0.591;
      94 m x min(-1), p = 0.426; 107 m x min(-1), p = 0.869). At 54 m x min(-1), the
      front, side, and back pedometers significantly underestimated hand-tally counted
      steps by 20 % (p < 0.001), 33 % (p < 0.001), and 26 % (p < 0.001), respectively.
      At 67 m x min(-1) the front, side, and back pedometers significantly
      underestimated hand-tally counted steps by 7 % (p = 0.027), 13 % (p < 0.001), 11
      % (p = 0.002), respectively. The steps recorded by the electronic pedometers
      placed at the front, side and back of the waist were not significantly different
      than steps counted by the hand-tally counter at speeds of 80 m x min(-1) and
      higher for all subjects combined. An electronic pedometer accurately quantified
      steps walked at speeds of 80 m x min(-1) or faster in persons with a normal BMI
      and those classified as overweight or obese. The placement of the pedometer on
      the front, side or back of the waistband did not affect accuracy of the pedometer
      for counting steps.

PMID- 14598196
TI  - Hip pain related to femoral neck stress fracture in a 12-year-old boy performing
      intensive soccer playing activities--a case report.
AB  - We describe the rare case of a 12-year-old boy complaining of repetitive severe
      pain in the left thigh, during physical activity related to a femoral neck stress
      fracture. Even though stress fractures are common in the adult athletic
      population, they occur rarely in children, with the epiphyseal growth plates
      still open. Diagnosis is delayed as only unspecific changes are found when
      conventional radiography is performed. For adequate treatment, early diagnosis by
      MRT or bone scintigraphy is essential. Conservative treatment will be effective
      through prevention of overuse.

PMID- 14598197
TI  - Kinematics of spinal motion during prolonged rowing.
AB  - Low back pain is a common problem in rowers of all levels. Few studies have
      looked at the relationship between rowing technique, the forces generated during
      the rowing stroke and the kinematics of spinal motion. Of particular concern with
      respect to spinal injury and damage are the effects of fatigue during long rowing
      sessions. A technique has been developed using an electromagnetic motion system
      and strain gauge instrumented load cell to measure spinal and pelvic motion and
      force generated at the handle during rowing on an exercise rowing ergometer.
      Using this technique 13 elite national and international oarsmen (mean age 22.43
      +/- 1.5 y) from local top squad rowing teams were investigated. The test protocol
      consisted of a one hour rowing piece. During this session rowing stroke profiles
      were quantified in terms of lumbopelvic kinematics and stroke force profiles.
      These profiles were sampled at the start of the session and at quarterly
      intervals during the hour piece. From this data we were able to quantify the
      motion of the lumbar spine and pelvis during rowing and relate this to the stroke
      force profile. The stroke profiles over the one hour piece were then compared to
      examine the effects of prolonged rowing. This revealed marked increases in the
      amount of spinal motion during the hour piece. The relevance of this with regard
      to low back pain requires further investigation.

PMID- 14598198
TI  - Maximal fat oxidation during exercise in trained men.
AB  - Fat oxidation increases from low to moderate exercise intensities and decreases
      from moderate to high exercise intensities. Recently, a protocol has been
      developed to determine the exercise intensity, which elicits maximal fat
      oxidation rates (Fat(max)). The main aim of the present study was to establish
      the reliability of the estimation of Fat(max) using this protocol (n = 10). An
      additional aim was to determine Fat(max) in a large group of endurance-trained
      individuals (n = 55). For the assessment of reliability, subjects performed three
      graded exercise tests to exhaustion on a cycle ergometer. Tests were performed
      after an overnight fast and diet and exercise regime on the day before all tests
      were similar. Fifty-five male subjects performed the graded exercise test on one
      occasion. The typical error (root mean square error and CV) for Fat(max) and
      Fat(min) was 0.23 and 0.33 l O(2) x min(-1) and 9.6 and 9.4 % respectively.
      Maximal fat oxidation rates of 0.52 +/- 0.15 g x min(-1) were reached at 62.5 +/-
      9.8 % VO(2)max, while Fat(min) was located at 86.1 +/- 6.8 % VO(2)max. When the
      subjects were divided in two groups according to their VO(2)max, the large spread
      in Fat(max) and maximal fat oxidation rates remained present. The CV of the
      estimation of Fat(max) and Fa(min) is 9.0 - 9.5 %. In the present study the
      average intensity of maximal fat oxidation was located at 63 % VO(2)max. Even
      within a homogeneous group of subjects, there was a relatively large inter
      individual variation in Fat(max) and the rate of maximal fat oxidation.

PMID- 14598199
TI  - Influence of physical activity on depression and anxiety of former elite
      athletes.
AB  - The purpose of this study was to investigate the influence of physical activity
      and other factors on the mood of former elite male athletes and controls of
      middle and old age. The subjects were 664 former athletes and 500 controls who
      answered questionnaires in 1985 and 1995. The dependent variables depressive and
      anxiety symptoms were assessed by the shortened anxiety and depression scales of
      the BSI-53. Logistic regression was used for longitudinal as well as cross
      sectional analyses to estimate odds ratios for symptoms of depression and anxiety
      in relation to leisure physical activity adjusted for age in 1995, sports group,
      personality characteristics, alcohol use, smoking, marital status, life events
      and socio-economic status. In the longitudinal analysis, low levels of physical
      activity as well as neuroticism, dissatisfaction, marital status, life events and
      social class in 1985 increased the risk of depression in 1995. Also physical
      activity has a protective effect against depressiveness; an increase of one MET
      unit (hour/day) statistically significantly decreased the risk of depressiveness
      by 8 %. In the longitudinal analysis, physical activity had no significant
      association with anxiety. Cross-sectional analysis for depressive symptoms in
      1995, but not for anxiety found associations with sports group and physical
      activity as well as alcohol use and marital status. Very high physical activity
      has a significant protective effect against depression.

PMID- 14598200
TI  - Nandrolone Progress Report to the UK Sports Council from the Expert Committee on
      Nandrolone February 2003.

PMID- 14598201
TI  - Immunomodulatory activity and chemical characterisation of sangre de drago
      (dragon's blood) from Croton lechleri.
AB  - The immunomodulatory activity of the latex from Croton lechleri (sangre de drago)
      was determined by in vitro assays. Classical (CP) and alternative (AP) complement
      pathways activities were determined in human serum. Intracellular generation of
      reactive oxygen species (ROS) by human polymorphonuclear leukocytes (PMNs) and
      monocytes, and phagocytosis of opsonised fluorescent microspheres were measured
      by flow cytometry. Free radical scavenging activity was evaluated using 1,1
      diphenyl-2-picrylhydrazyl (DPPH). Activity on proliferation of murine lymphocytes
      was also investigated. In addition, anti-inflammatory activity was assayed in
      vivo by carrageenan-induced rat paw oedema test. Some of the activities were
      compared with those of the isolated alkaloid taspine. Sangre de drago from Croton
      lechleri showed immunomodulatory activity. It exhibited a potent inhibitory
      activity on CP and AP of complement system and inhibited the proliferation of
      activated T-cells. The latex showed free radical scavenging capacity. Depending
      on the concentration, it showed antioxidant or prooxidant properties, and
      stimulated or inhibited the phagocytosis. Moreover, the latex has strong anti
      inflammatory activity when administered i. p. Taspine cannot be considered the
      main responsible for these activities, and other constituents, probably
      proanthocyanidins, should be also involved.

PMID- 14598202
TI  - Antinociceptive profile of (-)-spectaline: a piperidine alkaloid from Cassia
      leptophylla.
AB  - The antinociceptive activity of (-)-spectaline (1), a piperidine alkaloid
      isolated from Cassia leptophylla Vog. (Leguminosae), was investigated. We have
      also studied the acute oral toxicity of 1 in mice and it did not show any signals
      of toxicity in doses lower than 400 micromol/kg. The antinociceptive effect of 1
      was evaluated on chemical (acetic acid, formalin and capsaicin) and thermal (hot
      plate and tail flick) pain models in mice, using classical standard drugs.
      Dipyrone ID (50) = 14.68 micromol/kg (4.8 mg/kg), indomethacin ID (50) = 0.78
      micromol/kg (0.28 mg/kg) and (-)-spectaline ID (50) = 48.49 micromol/kg (15.75
      mg/kg), all produced a significant inhibition of acetic acid-induced abdominal
      writhing in mice. (-)-Spectaline was inactive in the hyperalgesic model of
      formalin and did not show any central analgesic activity (hot plate and tail
      flick models). In the capsaicin-induced neurogenic pain model, (-)-spectaline
      presented an important inhibitory effect with an ID (50) = 20.81 microg/paw and
      dipyrone ID (50) = 19.89 microg/paw. The ensemble of results permitted us to
      identify 1 as an antinociceptive compound. The mechanism underlying this
      antinociceptive effect of 1 remains unknown, but the results suggest that such an
      effect could be related to pathways associated to vanilloid receptor systems.

PMID- 14598203
TI  - 8-O-cinnamoylneoline, a new alkaloid from the flower buds of Aconitum carmichaeli
      and its toxic and analgesic activities.
AB  - From flower buds of Aconitum carmichaeli Debx., a new alkaloid, 8- O
      cinnamoylneoline, was isolated. The structure of the new alkaloid was determined
      by spectral analysis, and the alkaloid was examined for its toxic and analgesic
      activities. Its LD50 value was 11.89 mg/kg (s.c.) in mice: the toxicity was 1/30
      times that of mesaconitine and 20 times that of benzoylmesaconine. Its ED50 value
      was 0.86 mg/kg (s.c.) in mice using the tail pressure method: its analgesic
      effect was 1/40 times that of mesaconitine and 45 times that of
      benzoylmesaconine. Its safety margin (= LD50/ED50) was higher than that of
      benzoylmesaconine but lower than that of mesaconitine.

PMID- 14598204
TI  - Cytotoxic biotransformed products from triptonide by Aspergillus niger.
AB  - The diterpenoid triepoxides are the major active constituents of Tripterygium
      wilfordii with potent antitumor and immune activities. But the strong toxicity of
      these compounds has restricted their application to a great extent. In order to
      find more effective compounds with less toxicity, structural modifications of
      triptonide (1) by Aspergillus niger (AS 3.739) were investigated and four
      biotransformed products were obtained. Based on their chemical and spectral data,
      their structures were elucidated as 5alpha-hydroxytriptonide (2), triptolide (3),
      17-hydroxytriptonide (4), and 16-hydroxytriptonide (5), among which 2, 4 and 5
      are new compounds. All the three new transformed products showed cytotoxic
      activities against the majority of the human tumor cell lines tested, however,
      they are found to possess less cytotoxic activity when compared with 1. Both
      compounds 4 and 5 showed similar cytotoxic activity and their IC (50) values were
      5-15 fold less than 1, while 2 is about 100 times less active than 1.

PMID- 14598205
TI  - Mollisin, an antifungal protein from the chestnut Castanea mollissima.
AB  - The isolation of a protein designated mollisin, with an N-terminal sequence
      manifesting some similarity to thaumatin-like proteins (TLPs), and possessing a
      molecular mass of 28 kDa which is higher than those of TLPs, is reported herein
      from the seeds of the chestnut Castanea mollisima. The protein was unadsorbed on
      DEAE-cellulose, and adsorbed on Affi-gel blue gel and Mono S. Mollisin exhibited
      a molecular mass of 28 kDa in sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis as well as in gel filtration on Superdex 75 by fast protein
      liquid chromatography. The protein inhibited mycelial growth in Fusarium
      oxysporum, Mycosphaerella arachidicola and Physalospora piricola, with an IC (50)
      of 0.83 microM, 6.48 microM and 9.21 microM, respectively. Mollisin displayed a
      higher antifungal potency than French bean and kiwi fruit TLPs toward F.
      oxysporum and M. arachidicola. The antifungal activity of mollisin was unaffected
      by incubation at 40 degrees C for 10 minutes, underwent a decline after
      incubation at 60 degrees C, and was completely abolished after treatment at 80
      degrees C. Mollisin exhibited a more potent inhibitory activity on HIV-1 reverse
      transcriptase than kiwi fruit TLP.

PMID- 14598206
TI  - Wiedemanniosides A-E: new phenylethanoid glycosides from the roots of Verbascum
      wiedemannianum.
AB  - From the aerial parts of Verbascum wiedemannianum Fisch. & Mey. four new
      phenylethanoid glycosides (wiedemanniosides B - E) were isolated along with four
      known compounds; 6- O-acetylmartynoside (= wiedemanniosides A), verbascoside,
      martynoside, echinacoside and leucosceptoside B. The structures of the new
      compounds were elucidated by employing spectroscopic techniques (NMR, HR-ESIMS,
      IR, and UV).

PMID- 14598207
TI  - New and known iridoid- and phenylethanoid glycosides from Harpagophytum
      procumbens and their in vitro inhibition of human leukocyte elastase.
AB  - Ten compounds, harpagoside (1), 8- p-coumaroylharpagide (2), 8-feruloylharpagide
      (3), 8-cinnamoylmyoporoside (4), pagoside (5), acteoside (6), isoacteoside (7),
      6'- O-acetylacteoside (8), cinnamic acid (9) and caffeic acid (10) were isolated
      from the storage roots of Harpagophytum procumbens, Pedaliaceae. Compounds 1, 2,
      6, 7 and 9 are known for H. procumbens; 3 and 10 were isolated the first time
      from H. procumbens; compounds 4, 5 and 8 are new natural products. Their
      structures were elucidated using spectroscopic data (NMR, with NOE, COSY and HMBC
      experiments, UV, [alpha]). The inhibitory activity of aqueous extracts of the
      roots of H. procumbens and H. zeyheri as well as the main compounds isolated from
      H. procumbens was tested on human neutrophile elastase. Although inhibition was
      comparatively weak a dose-dependence was observed. An IC (50) of 542 microg/mL
      was determined for the aqueous extract of H. procumbens, but 1012 microg/mL for
      that of H. zeyheri. 6'- O-Acetylacteoside (8), that is not present in H. zeyheri,
      inhibited the enzyme with an IC (50) of 47 microg/mL (70 microM), compound 7 with
      179 microg/mL (286 microM), 2 with 179 microg/mL (331 microM), 5 with 154
      microg/mL (260 microM) and 10, which was also used as reference compound, with an
      IC (50) of 86 microg/mL (475 microM). The IC (50) values of acteoside,
      harpagoside, cinnamic acid and stachyose were higher than 300 microg/mL and thus
      not further determined.

PMID- 14598208
TI  - Constituents from the stems of Goniothalamus griffithii.
AB  - A new cyclopeptide, grifficyclocin A (1), and a new aporphine alkaloid, griffinin
      (2) were isolated together with two known styryllactones from the stems of
      Goniothalamus griffithii. Their structures were identified spectroscopically and
      chemically. Among them, the griffinin (2) was isolated as the enol form in two
      tautomers, and the two known styryllactones, goniothalamin (3) and 8- O
      acetylgoniotriol (4), showed selective in vitro antitumor activities.

PMID- 14598209
TI  - A new antioxidant isobenzofuranone derivative from the algicolous marine fungus
      Epicoccum sp.
AB  - The fungus Epicoccum sp., was isolated from the marine brown alga Fucus
      vesiculosus. After cultivation the fungus was investigated for its secondary
      metabolite content, and found to contain the new natural product 4,5,6-trihydroxy
      7-methylphthalide (1, epicoccone), together with 5-(acetoxymethyl)-furan-2
      carboxylic acid (2), furan-2-carboxylic acid (3), 5-(hydroxymethyl)-furan-2
      carboxylic acid (4), (-)-(3 R,4 S)-4-hydroxymellein (5), and (-)-(3 R)-5
      hydroxymellein (6). The structures of all compounds were determined by
      interpretation of their spectroscopic data (1D and 2D NMR, MS, UV, optical
      rotation and IR). Each isolate was tested for its antioxidative properties.
      Compound 1 was found to be potently active, showing 95 % DPPH radical scavenging
      effects at 25 microg/mL. Compound 1 also inhibited the peroxidation of linolenic
      acid in the TBARS assay (62 % inhibition at 37 microg/mL).

PMID- 14598210
TI  - New Pyrrolizidine Alkaloids and Glycosides from Anchusa strigosa.
AB  - Six new pyrrolizidine alkaloids, a new carboxylic acid, a new phenolic and a new
      oleanane glycoside, together with the known compounds 7,7'-bis-(4-hydroxy-3,5
      dimethoxyphenyl)-8,8'-dihydroxymethyltetrahydrofuran 4'-O-beta-D-glucopyranoside,
      rosmarinic acid, caffeic acid, tormentic acid 28-O-beta- D-glucopyranoside,
      euscaphic acid 28-O-beta-D-glucopyranoside, euscaphic acid, and allantoin were
      isolated from Anchusa strigosa roots. Their structures were established by high
      resolution NMR, MS, elemental analysis, and chemical reactions.

PMID- 14598211
TI  - Cytotoxic alkaloids from Boehmeria siamensis.
AB  - Two new phenanthroquinolizidine alkaloids, boehmeriasins A and B, were isolated
      from the aqueous ethanolic extract of Boehmeria siamensis Craib (Urticaceae) by
      bioassay-guided fractionation. Their structures were elucidated on the basis of
      spectral evidence. Boehmeriasin A possesses cytotoxic activity against 12 cell
      lines from 6 panels of cancer including lung cancer, colon cancer, breast cancer,
      prostate cancer, kidney cancer and leukemia with GI (50) between 0.2 and 100
      ng/mL, whereas boehmeriasin B showed lower activity.

PMID- 14598212
TI  - Terpenoids of Salvia hydrangea: two new, rearranged 20-norabietanes and the
      effect of oleanolic acid on erythrocyte membranes.
AB  - Four abietane-type terpenoids, including two known royleanones and two new,
      rearranged 20-norabietanes, were isolated from the roots of the Iranian medicinal
      plant Salvia hydrangea DC. ex Bentham (Lamiaceae), which is used as an
      anthelmintic and antileishmanial remedy. Their structures were established using
      COSY, NOESY, HSQC, and HMBC spectral data. The possible identity of one of the 20
      norabietanes with demethylmulticauline, previously reported from a different
      Salvia species, is discussed. A moderate in vitro antiplasmodial effect of the
      extract of S. hydrangea flowers was found to be associated with the presence of
      large amounts of pentacyclic triterpenes, mainly oleanolic acid. The observed
      antiplasmodial activity of oleanolic acid is apparently due to its incorporation
      into the erythrocyte membrane, which adversely affects the growth of Plasmodium
      falciparum parasites. Thus, oleanolic acid caused transformation of erythrocytes
      into stomatocytes in the concentration range where the in vitro antiplasmodial
      activity was observed.

PMID- 14598213
TI  - Ternatin, an anti-inflammatory flavonoid, inhibits thioglycolate-elicited rat
      peritoneal neutrophil accumulation and LPS-activated nitric oxide production in
      murine macrophages.
AB  - Ternatin, an anti-inflammatory flavonoid from Egletes viscosa Less., was examined
      for its possible influence on thioglycolate-elicited neutrophil influx into the
      rat peritoneal cavity in vivo and nitric oxide production in lipopolysaccharide
      (LPS)-activated mouse peritoneal macrophages ex vivo. The neutrophil influx
      induced by thioglycolate was found to be significantly lower in ternatin (25 and
      50 mg/kg, s. c.) pre-treated rats with a similar magnitude of inhibition produced
      by dexamethasone (1 mg/kg, s. c.), a known anti-inflammatory agent. Also,
      peritoneal macrophages from ternatin (25 mg/kg)-treated mice that were exposed to
      LPS demonstrated significantly less production of nitric oxide (NO). These
      results suggest that ternatin exerts its anti-inflammatory action, at least in
      part, through inhibition of neutrophil migration and modulation of macrophage
      function.

PMID- 14598214
TI  - A flavone from Manilkara indica as a specific inhibitor against aldose reductase
      in vitro.
AB  - Isoaffinetin (5,7,3',4',5'-pentahydroxyflavone-6-C-glucoside) was isolated from
      Manilkara indica as a potent inhibitor of lens aldose reductase by bioassay
      directed fractionation. This C-glucosyl flavone showed specific inhibition
      against aldose reductases (rat lens, porcine lens and recombinant human) with no
      inhibition against aldehyde reductase and NADH oxidase. Kinetic analysis showed
      that isoaffinetin exhibited uncompetitive inhibition against both dl
      glyceraldehyde and NADPH. A structure-activity relationship study revealed that
      the increasing number of hydroxy groups in the B-ring contributes to the increase
      in aldose reductase inhibition by C-glucosyl flavones.

PMID- 14598215
TI  - Antiandrogenic activity of the phytoestrogens naringenin, 6-(1,1
      dimethylallyl)naringenin and 8-prenylnaringenin.
AB  - Naturally occurring naringenin derivatives, known for their estrogenic activity,
      were tested in two independent (anti-)androgen screening assays. Using a yeast
      based androgen receptor assay relatively strong antiandrogen activities were
      demonstrated for 6-(1,1-dimethylallyl)naringenin and 8-prenylnaringenin, while
      the parent compound naringenin did not show recognizable antiandrogen activity.
      In an androgen receptor activity assay based on the analysis of prostate specific
      antigen (PSA) concentrations in the supernatants of treated PC3(AR)2 cells the
      antiandrogenic activity of 6-(1,1-dimethylallyl)naringenin was detected at
      concentrations of 10 (-5) M. 8-Prenylnaringenin or naringenin have no detectable
      antiandrogenic effect. In summary, for the first time we provide evidence of the
      antiandrogenic activity of 6-DMA-N in two independent model systems. In
      conclusion, we demonstrated the ability of prenylated naringenins not only to act
      via the estrogen receptor but also through the androgen receptor.

PMID- 14598216
TI  - A new anti-HIV flavonoid glucuronide from Chrysanthemum morifolium.
AB  - A new flavonoid glucuronide, apigenin 7-O-beta-D-(4'-caffeoyl)glucuronide (1),
      and the known compound, apigenin 7-O-beta-D-glucurnoide, were isolated from the
      flowers of Chrysanthemum morifolium, along with five known flavonoids. The
      structure of 1 was elucidated by the aid of spectroscopic analyses. Among
      isolated compounds, apigenin 7-O-beta-D-(4"-caffeoyl)glucuronide showed strong
      HIV-1 integrase inhibitory activity (IC (50) = 7.2 +/- 3.4 microg/ml) and anti
      HIV activity in a cell culture assay (EC (50) = 41.86 +/- 1.43 microg/ml) using
      HIV-I (IIIB) infected MT-4 cells.

PMID- 14598217
TI  - Preventive agents against sepsis and new phenylpropanoid glucosides from the
      fruits of Illicium verum.
AB  - The bioassay-guided fractionation of preventive agents against lethality due to
      septic shock from the fruits of Illicium verum led to the isolation of two known
      racemic mixtures of phenylpropanoids, [1-(4'-methoxyphenyl)-(1 R,2 S and 1 S,2 R)
      propanediol (1) and 1-(4'-methoxyphenyl)-(1 R,2 R and 1 S,2 S)-propanediol (2)],
      along with two known phenylpropanoid glucosides, [1-(4'-methoxyphenyl)-(1 S,2 R)
      propan-1-ol 2-O-beta-D-glucopyranoside (3) and 1-(4'-methoxyphenyl)-(1 R,2 S)
      propan-1-ol 2-O-beta-D-glucopyranoside ( 5)], and two new phenylpropanoid
      glucosides, [1-(4'-methoxyphenyl)-(1 S,2 S)-propan-1-ol 2- O-beta- D
      glucopyranoside (4) and 1-(4'-methoxyphenyl)-(1 R,2 R)-propan-1-ol 2-O-beta-D
      glucopyranoside (6)]. Their chemical structures were elucidated on the basis of
      spectroscopic studies. Among them, 1 exhibited the highest survival rate in a
      dose-dependent manner (100 % with a dose of 10 mg/kg against 40 % for the control
      experiment) and showed a reduction of the plasma alanine aminotransferase (ALT)
      value on the in vivo assay model of septic shock induced by tumor necrosis factor
      (TNF)-alpha.

PMID- 14598219
TI  - Cytotoxic and DNA damaging activity of some aporphine alkaloids from Stephania
      dinklagei.
AB  - Six aporphine alkaloids, liriodenine, corydine, isocorydine, atherospermidine,
      stephalagine and dehydrostephalagine, were isolated by bioassay-guided
      fractionation of the EtOH extract of the stems of Stephania dinklagei.
      Liriodenine showed strong cytotoxic activity while corydine and atherospermidine
      showed DNA damaging activity. Dehydrostephalagine and atherospermidine were
      isolated from this plant for the first time.

PMID- 14598218
TI  - A novel cytotoxic guttiferone analogue from Garcinia macrophylla from the
      Suriname rainforest.
AB  - Bioassay-guided fractionation of the EtOAc extract of the twigs of Garcinia
      macrophylla from Suriname produced the known benzophenone, guttiferone A (1), and
      a new guttiferone analogue, guttiferone G (2). Friedelin was also isolated. The
      structures of compounds 1 and 2 were elucidated using 1D and 2D NMR spectroscopy.
      Compounds 1 and 2 were weakly cytotoxic in the A2780 human ovarian cell line,
      with IC (50) values of 6.8 and 8.0 microg/mL, respectively.

PMID- 14598220
TI  - Galanthindole: a new indole alkaloid from Galanthus plicatus ssp. byzantinus.
AB  - A new indole alkaloid, galanthindole, was isolated from Galanthus plicatus ssp.
      byzantinus (Amaryllidaceae), a plant native to northwestern Turkey. Incorporating
      a non-fused indole ring, galanthindole may represent the prototype of a new
      subgroup of the Amaryllidaceae alkaloids. Two other bases, (+)-11
      hydroxyvittatine and hordenine, are also reported from the same plant.

PMID- 14598221
TI  - Chemical composition and antifungal activity of the essential oil of Origanum
      virens on Candida species.
AB  - The composition and the antifungal activity of the essential oil of Origanum
      virens on Candida species were studied. The essential oil was obtained from the
      aerial parts of the plant by hydrodistillation and analyzed by GC and GC-MS. The
      oil was characterized by its high content of carvacrol (68.1 %) and its
      biogenetic precursors, gamma-terpinene (9.9 %) and p-cymene (4.5 %). The minimal
      inhibitory concentration (MIC) and the minimal lethal concentration (MLC) were
      used to evaluate the antifungal activity against Candida strains (7 clinical
      isolates and 3 ATCC type strains). The inhibition of germ tube formation and flow
      cytometry, using the fluorescent probe propidium iodide (PI), were used to
      evaluate their mechanisms of action. MIC and MLC values were similar for most
      tested strains, ranging from 0.16 to 0.32 microL/mL. Concentrations lower than
      MIC values strongly prevent germ tube formation. The fungicidal effect is
      primarily due to an extensive lesion of the membrane.

PMID- 14598222
TI  - Myorelaxant effects of the essential oil of Croton nepetaefolius on the
      contractile activity of the guinea-pig tracheal smooth muscle.
AB  - The effects of the essential oil of Croton nepetaefolius (EOCN) on isolated
      guinea-pig trachea were investigated. EOCN decreased the preparation's basal tone
      (EC (50) = 4.3 microg/mL) with a maximal effect similar to that of aminophylline.
      EOCN fully relaxed preparations pre-contracted with 60 mM K+ (IC (50) = 113.0
      microg/mL). EOCN did not alter the E (m) of smooth muscle cells in 5 and 80 mM
      K+. EOCN, at 300 and 600 microg/mL, reduced the contraction induced by ovalbumin
      (10 microg/mL) from 227.2 to 82.5 and 35.5 % of the 60 mM K+-induced contraction,
      respectively. EOCN blocked the submaximal contractions induced by histamine,
      carbachol and 60 mM K+ with a similar potency (IC (50) values = 123.9, 102.5 and
      128.8 microg/mL, respectively). In conclusion, EOCN exerts respiratory smooth
      muscle antispasmodic activity by a mechanism that is probably myogenic and not
      specific for neurotransmitters and autacoids.

PMID- 14598223
TI  - Iridoid glucosides from the flowers of Barleria lupulina.
AB  - A new iridoid diglucoside, lupulinoside, and eight known iridoid glucosides,
      acetylbarlerin, ipolamiidoside ( 3), 6-O-acetylshanzhiside methyl ester,
      barlerin, shanzhiside methyl ester, mussaenosidic acid, 8-O-acetylshanzhiside,
      and shanzhiside have been isolated from the flowers of Barleria lupulina. The
      structure of the new compound was established as 8-O-acetyl-2'- O-(beta
      glucopyranosyl)mussaenoside by spectroscopic, especially 2D NMR, techniques. When
      tested for anti-herpes simplex type 1 activity, only compound 3 exhibited
      antiviral properties. None of the compounds showed cytotoxic effects to the vero
      cells and none of them inhibited cyclooxygenase-2 enzyme.

PMID- 14598224
TI  - New guaianolides from leaves and stems of Chrysanthemum boreale.
AB  - The 8-acetoxy-2-methoxy-10-hydroxy-3,11(13)-guaiaden-12,6-olide 1 and 8,10
      diacetoxy-2-methoxy-3,11(13)-guaiadiene-12,6-olide 2 were isolated from
      Chrysanthemum boreale Makino. Compound 1 inhibited the etoposide-induced
      apoptosis in U 937 cells with an IC50 value 8.6 microg/mL.

PMID- 14598225
TI  - Molecular detection of cashew husk (Anacardium occidentale) adulteration in
      market samples of dry tea (Camellia sinensis).
AB  - Species-specific PCR primers were developed from intergenic spacer regions of 5S
      ribosomal RNA genes and used successfully in the detection of adulteration of
      cashew husk (Anacardium occidentale L.) in tea [Camellia sinensis (L.) O. Kuntze]
      samples. This is the first report of detecting adulteration in tea using
      molecular tools. Application of this approach in detecting adulteration of other
      biological materials in tea, medicinal herbs and the composition of admixtures of
      ayurvedic herbs has been discussed.

PMID- 14598228
TI  - Mutation analysis of the leucine-rich, glioma inactivated 1 gene (LGI1) in
      Japanese febrile seizure patients.
AB  - Mutations in the leucine-rich, glioma inactivated 1 gene (LGI1) were recently
      identified in some families with autosomal dominant lateral temporal epilepsy
      (ADLTE). To investigate whether the LGI1 gene is a susceptibility gene for
      febrile seizures (FS), we performed a systematic search for mutations in 94
      unrelated Japanese patients with FS. We detected two intronic polymorphisms (IVS2
      + 19 A/G and IVS6 - 18 T/C). No non-synonymous mutation was detected. We
      genotyped these polymorphisms and performed a case-control study and transmission
      disequilibrium testing (TDT) of 62 FS families (n = 230) and 105 control
      subjects. None of the polymorphisms was significantly associated with FS. Our
      results indicate that genomic variations in the LGI1 gene are not likely to be
      substantially involved in the etiology of FS in the Japanese population.

PMID- 14598227
TI  - Functional magnetic resonance imaging in pediatrics.
AB  - Functional magnetic resonance imaging (fMRI) allows non-invasive assessment of
      human brain function in vivo by detecting blood flow differences. In this review,
      we want to illustrate the background and different aspects of performing
      functional magnetic resonance imaging (fMRI) in the pediatric age group. An
      overview over current and future applications of fMRI will be given, and typical
      problems, pitfalls, and benefits of doing fMRI in the pediatric age group are
      discussed. We conclude that fMRI can successfully be applied in children and
      holds great promise for both research and clinical purposes.

PMID- 14598229
TI  - Quantitative proton magnetic resonance spectroscopy of children with
      adrenoleukodystrophy before and after hematopoietic stem cell transplantation.
AB  - About 35-40 % of boys with X-linked adrenoleukodystrophy (ALD) develop a rapidly
      progressive cerebral form which leads to severe neurologic disability and death
      within 3-5 years after onset of clinical symptoms. Because previous proton
      magnetic resonance spectroscopy (MRS) studies of ALD identified metabolite
      patterns characteristic of demyelination, gliosis, and neuroaxonal loss, this
      work tested the hypothesis that MRS--apart from indicating disease progression-
      provides criteria for the outcome after hematopoietic stem cell transplantation
      (HSCT) which has been promising at an early stage of the active disease. Follow
      up quantitative proton MRS was performed in frontal and occipital white matter of
      ALD patients (n = 12) before and up to 5 years after HSCT. The observed
      metabolite alterations were retrospectively correlated with the clinical outcome
      representing either a stable condition (n = 5), a further deterioration (n = 5),
      or death (n = 2). While disease progression of patients before HSCT was mainly
      characterized by a further increase of elevated choline-containing compounds
      (Cho) as an indicator of active demyelination, a positive outcome after HSCT was
      correlated with high N-acetylaspartate (tNAA) levels in affected white matter
      before HSCT yielding positive and negative predictive values for tNAA of 80 %.
      Although to be confirmed in a larger cohort of patients, the present findings
      suggest the preservation of neuroaxonal integrity as a prerequisite for an
      arrested course. Conversely, the combination of increased Cho with markedly
      reduced tNAA before HSCT apparently reflects a degree of tissue degeneration
      which precludes a successful therapeutic intervention.

PMID- 14598230
TI  - Correlation of corpus callosal morphometry with cognitive and motor function in
      periventricular leukomalacia.
AB  - PURPOSE: We aim to correlate size and shape of corpus callosum with severity of
      motor and cognitive impairments in children with periventricular leukomalacia
      (PVL). METHODS: Children with PVL were stratified based on the severity of their
      motor and cognitive impairments. An age-matched control group was established.
      The corpus callosum was identified on mid-sagittal T (1)-weighted spin-echo
      (TR/TE: 550/15) MR images. The shape characteristics of the corpus callosum were
      measured with respect to a template via a shape transformation. The degree of
      callosal-shape transformation was quantified by a deformation function, which in
      turn was compared, using point-wise T-tests, for controls versus patients,
      diplegic versus quadriplegic patients, and patients with mild versus severe
      cognitive impairment. RESULTS: 29 children with spastic cerebral palsy and PVL
      and 32 age-matched controls were identified. In the PVL group, the entire corpus
      callosum was significantly smaller than in the control group (p value = 0.001).
      Significant differences existed in the shape of the corpus callosum between
      patients with diplegic versus quadriplegic and between patients with severe
      versus mild cognitive impairment. CONCLUSION: Global and regional corpus callosal
      morphology can be quantified using deformation functions.

PMID- 14598231
TI  - Glutaryl-CoA dehydrogenase deficiency: region-specific analysis of organic acids
      and acylcarnitines in post mortem brain predicts vulnerability of the putamen.
AB  - The neurometabolic disorder glutaryl-CoA dehydrogenase (GCDH) deficiency is
      biochemically characterised by an accumulation of the marker metabolites 3
      hydroxyglutaric acid, glutaric acid, and glutarylcarnitine. If untreated, the
      disease is complicated by acute encephalopathic crises, resulting in
      neurodegeneration of vulnerable brain regions, in particular the putamen. 3
      hydroxyglutaric acid is considered the major neurotoxin in this disease. There
      are only preliminary data concerning glutaric acid concentrations in the brains
      of affected children and the distribution of 3-hydroxyglutaric acid and
      glutarylcarnitine has not been described. In the present study, we investigated
      post mortem the distribution of 3-hydroxyglutaric and glutaric acids as well as
      glutarylcarnitine in 14 different brain regions, internal organs, and body fluids
      (urine, plasma, cerebrospinal fluid) in a 14-year-old boy. 3-Hydroxyglutaric acid
      showed the highest concentration (62 nmol/g protein) in the putamen among all
      brain areas investigated. The glutarylcarnitine concentration was also highest in
      the putamen (7.1 nmol/g protein). We suggest that the regional-specific
      differences in the relative concentrations of 3-hydroxyglutaric acid contribute
      to the pattern of neuronal damage in this disease. These results provide an
      explanatory basis for the high vulnerability of the putamen in this disease,
      adding to the strong corticostriatal glutamatergic input into the putamen and the
      high excitotoxic susceptibility of neostriatal medium spiny neurons.

PMID- 14598232
TI  - Infantile cobalamin deficiency with cerebral lactate accumulation and sustained
      choline depletion.
AB  - A remarkable, intermittent sudden-onset vigilance and movement disorder in an
      exclusively breast-fed infant is reported, which was caused by cobalamin
      depletion due to maternal vitamin B12 malabsorption. The lack of cobalamin caused
      a severe encephalopathy in the infant, whose brain displayed a striking loss of
      volume and a delay of myelination. Proton magnetic resonance spectroscopy
      revealed an accumulation of lactate in the gray and white matter of the brain and
      a sustained depletion of choline-containing compounds in the white matter,
      reflecting a reversible disturbance of oxidative energy metabolism in brain cells
      and a long-lasting hypomyelination disorder. The clinical picture in conjunction
      with MRI and spectroscopic data of this case study yields more insight into the
      functions of cobalamin in the cerebral metabolism.

PMID- 14598233
TI  - Infantile spasms with basal ganglia MRI hypersignal may reveal mitochondrial
      disorder due to T8993G MT DNA mutation.
AB  - PURPOSE: To report three cases of infantile spasms (IS) with an abnormal magnetic
      resonance imaging signal in the basal ganglia (Leigh-like syndrome), due to
      T8993G mt DNA mutation. PATIENTS AND RESULTS: The first sign was, at the end of
      the first year of life, IS in one case and the combination of IS with behavior
      changes in the two other cases. Video EEG polygraphy demonstrated both spasms and
      hypsarrhythmia, but no other kind of seizures. Vigabatrin or steroids controlled
      the spasms with a follow-up of several years. All 3 patients had
      hyperlactatorrhachia (3.47 to 7 mmol/l). Axial hypotonia and dystonia appeared by
      the end of the first year of life. As in cases with the NARP mutation and onset
      later in life, neuropathy and retinopathy could also be demonstrated. DISCUSSION:
      Although it is well established that symptomatic IS with hypsarrhythmia mainly
      result from cortical lesions, this epileptic encephalopathy may also be generated
      by lesions in the basal ganglia without evidence of cortical damage. This finding
      suggests that West syndrome is likely to be caused by age-related dysfunction at
      any level of a cortico-putaminal loop of hyperexcitability.

PMID- 14598234
TI  - Identification of a novel LAMP2 mutation responsible for X-chromosomal dominant
      Danon disease.
AB  - Danon disease (DD) is a rare lysosomal glycogen storage disease with normal acid
      maltase activity, which is characterised clinically by cardiomyopathy and
      myopathy, and a variable degree of mental retardation. The causative gene, LAMP2,
      has been mapped to chromosome Xq24-q25. LAMP2 encodes a lysosome-associated
      membrane glycoprotein. We identified a novel LAMP2 mutation of the exon 8 splice
      acceptor site (IVS7-1G --> A) in an affected male and female, which predicts
      abnormal splicing. Both affected individuals presented solely with hypertrophic
      cardiomyopathy. Muscle weakness and mental impairment were absent. Diagnosis of
      Danon disease was established by muscle biopsy, when the male index patient
      developed transient severe muscle weakness following heart transplantation.
      Typical biopsy findings were also found in a heart muscle specimen. Demonstration
      of the LAMP2 mutation in affected male and female siblings is compatible with X
      linked dominant inheritance. Danon disease should be actively looked for in
      cardiomyopathy patients.

PMID- 14598235
TI  - Acute ophthalmoparesis in a child with anti-GQ1 b IgG antibody.

PMID- 14598236
TI  - Antibody positive myasthenia gravis following treatment with carbamazepine--a
      chance association?

PMID- 14598237
TI  - Isolated recurrent palatal palsy in a child.

PMID- 14598239
TI  - HIPAA challenges to clinical research.

PMID- 14598240
TI  - AGA urges creation of digestive diseases research commission.

PMID- 14598241
TI  - Multicenter study to explore drug-induced liver injury.

PMID- 14598242
TI  - This month at the NIH: NIH FY2004 loan repayment program for clinical and
      pediatric researchers.

PMID- 14598244
TI  - The flexible Ph.D.

PMID- 14598243
TI  - Rontgen of roentgenology.

PMID- 14598245
TI  - Image of the month: primary amyloidosis of the duodenum.

PMID- 14598246
TI  - Defects in cholangiocyte fibrocystin expression and ciliary structure in the PCK
      rat.
AB  - BACKGROUND & AIMS: Recent studies have showed that proteins associated with
      polycystic kidney disease (PKD) are expressed in cilia, linking this organelle
      and cyst formation in the kidney, but involvement of cilia in PKD-related biliary
      cystogenesis has not been shown. We investigated: (1) the expression of
      fibrocystin (a product of PKHD1, the autosomal-recessive PKD [ARPKD] gene) in
      cholangiocyte cilia; (2) biliary cyst formation in an orthologous rat model, PCK;
      and (3) the effect of Pkhd1 mutation on ciliary structure. METHODS: Biliary
      cystogenesis was assessed by microcomputed tomography. Fibrocystin expression in
      cholangiocytes of isolated intrahepatic bile ducts (IBDUs) and liver cysts was
      analyzed by confocal and immunoelectron microscopy, and ciliary structure and
      length by scanning and transmission electron microscopy. Small interfering RNAs
      (siRNA) were used to examine the effect of fibrocystin loss on ciliary structure.
      RESULTS: The biliary tree in the PCK rat was distorted markedly, showing multiple
      bile duct dilatation and focal budding. In normal IBDUs, each cholangiocyte had a
      single cilium that expressed fibrocystin. In contrast, cilia in the PCK rat were
      abnormal with bulbous extensions and diminished length, and were devoid of
      fibrocystin. In cholangiocytes of normal IBDUs, specific siRNA reduced Pkhd1
      messenger RNA by 80%, the length of cilia by 41%, and fibrocystin ciliary
      expression to an undetectable level. CONCLUSIONS: Our results indicate that
      fibrocystin is expressed in cholangiocyte cilia and that disruption of Pkhd1 by a
      germ line mutation in the PCK rat or by siRNA in IBDUs results in abnormalities
      in ciliary morphology and possibly biliary cystogenesis.

PMID- 14598247
TI  - Progression of flat low-grade dysplasia to advanced neoplasia in patients with
      ulcerative colitis.
AB  - BACKGROUND & AIMS: Long-standing ulcerative colitis has long been recognized as a
      risk factor for colorectal cancer, but there is still no universal consensus on
      the optimal management of ulcerative colitis patients with low-grade dysplasia in
      flat mucosa. Some authorities favor prompt colectomy, whereas others recommend
      continued surveillance. The purpose of our study was to determine the frequency
      with which flat low-grade dysplasia in ulcerative colitis progresses to advanced
      neoplasia (high-grade dysplasia or colorectal cancer) and whether specific
      variables could predict such progression. METHODS: We reviewed the medical
      histories, colonoscopic findings, and surgical and pathology reports of 46
      patients with ulcerative colitis diagnosed with flat low-grade dysplasia on a
      surveillance colonoscopy. The rates of neoplastic progression, as well as the
      frequency of advanced neoplasia, were tabulated. We correlated progression with
      several clinical and colonoscopic variables: the number of biopsy samples
      positive for flat low-grade dysplasia, the duration and anatomic extent of
      disease, patient age, and medication use. RESULTS: Among these 46 patients, there
      were 7 cases of colorectal cancer, 5 of which were stage II or higher. Unexpected
      advanced neoplasia occurred in 4 of 17 (23.5%) patients who underwent colectomy
      for flat low-grade dysplasia. On an actuarial basis, the rate of neoplastic
      progression was 53% at 5 years. No clinical features predicted progression to
      advanced neoplasia. Cancers, including 2 at advanced stages, developed despite
      frequent follow-up surveillance examinations. CONCLUSIONS: A finding of flat low
      grade dysplasia during ulcerative colitis surveillance is a strong predictor of
      progression to advanced neoplasia. Early colectomy should be recommended for such
      patients.

PMID- 14598248
TI  - Randomized controlled trial of biofeedback for fecal incontinence.
AB  - BACKGROUND & AIMS: Behavioral treatment (biofeedback) has been reported to
      improve fecal incontinence but has not been compared with standard care. METHODS:
      A total of 171 patients with fecal incontinence were randomized to 1 of 4 groups:
      (1) standard care (advice); (2) advice plus instruction on sphincter exercises;
      (3) hospital-based computer-assisted sphincter pressure biofeedback; and (4)
      hospital biofeedback plus the use of a home electromyelogram biofeedback device.
      Outcome measures included diary, symptom questionnaire, continence score,
      patient's rating of change, quality of life (short-form 36 and disease specific),
      psychologic status (Hospital Anxiety and Depression scale), and anal manometry.
      RESULTS: Biofeedback yielded no greater benefit than standard care with advice
      (53% improved in group 3 vs. 54% in group 1). There was no difference between the
      groups on any of the following measures: episodes of incontinence decreased from
      a median of 2 to 0 per week (P < 0.001). Continence score (worst = 20) decreased
      from a median of 11 to 8 (P < 0.001). Disease-specific quality of life, short
      form 36 (vitality, social functioning, and mental health), and Hospital Anxiety
      and Depression scale all significantly improved. Patients improved resting,
      squeeze, and sustained squeeze pressures (all P < 0.002). These improvements were
      largely maintained 1 year after finishing treatment. CONCLUSIONS: Conservative
      therapy for fecal incontinence improves continence, quality of life, psychologic
      well-being, and anal sphincter function. Benefit is maintained in the medium
      term. Neither pelvic floor exercises nor biofeedback was superior to standard
      care supplemented by advice and education.

PMID- 14598249
TI  - The genomic damage estimated by arbitrarily primed PCR DNA fingerprinting is
      useful for the prognosis of gastric cancer.
AB  - BACKGROUND & AIMS: Genomic instability and the accompanying alteration of cancer
      genes play a major role in tumorigenesis. We evaluated the prognostic
      significance in gastric cancer of the degree of accumulation of relative genomic
      damage, assessed by arbitrarily primed polymerase chain reaction DNA
      fingerprinting. METHODS: Genomic damage was assessed by comparative analysis of
      paired normal and tumor tissue DNA fingerprints. The total number of alterations,
      scored as decreases and increases of band intensity with 2 arbitrary primers,
      were used as an estimation of the genomic damage fraction in 74 primary gastric
      cancers. Increases in DNA copy number were also analyzed by array comparative
      genomic hybridization in a subset of 30 cases. RESULTS: The number of altered
      bands varied among the tumors from none or a few to more than one third of the
      approximately 40 fingerprint bands. The relative values of genomic damage were
      consistent with the quantitative chromosomal alterations observed by array
      comparative genomic hybridization. When the tumors were stratified into 2 groups
      above or below the cutoff of 0.22 for average genomic damage fraction-genomic
      damage fraction was a valuable prognostic indicator regardless of microsatellite
      instability status. Multivariate Cox analysis showed that the genomic damage
      fraction was a prognostic indicator, as well as a stage indicator (P = 0.0189).
      Survival was significantly diminished in tumors with a genomic damage fraction
      >0.22 (P = 0.0009). Moreover, in the 46 curative cases, genomic damage fraction
      was the only independent factor for predicting survival (P = 0.0061).
      CONCLUSIONS: Our results indicate that the degree of genomic damage estimated by
      arbitrarily primed polymerase chain reaction fingerprinting is a useful
      prognostic indicator for gastric cancer.

PMID- 14598250
TI  - Reduced migration of fibroblasts in inflammatory bowel disease: role of
      inflammatory mediators and focal adhesion kinase.
AB  - BACKGROUND & AIMS: Crohn's disease (CD) and ulcerative colitis (UC) are
      associated with chronic tissue damage and continuous tissue repair. A central,
      but not well-characterized, event during this process is the migration of
      activated fibroblasts to the wound. METHODS: Human colonic lamina propria
      fibroblasts (CLPF) were isolated from patients with CD and UC and from healthy
      controls and were characterized by immunocytochemistry. Migration assays of CLPF
      were performed in the modified 48-well Boyden chamber. Focal adhesion kinase
      (FAK) and FAK autophosphorylation in migrating CLPF were determined by Western
      blotting. FAK mRNA expression was investigated by Northern blotting. RESULTS: The
      migration of CD-CLPF and UC-CLPF was significantly reduced when compared with
      control-CLPF. This was correlated with a decrease in FAK phosphorylation,
      whereas, in migrating control-CLPF, an increase was found. Similarly, the
      presence of the inflammatory mediators interferon (IFN)-gamma (50 ng/mL) or tumor
      necrosis factor (TNF) (30 ng/mL) in conditioned medium significantly reduced the
      migration of control-CLPF to 41% +/- 4% or 30% +/- 7%, respectively.
      Preincubation of control-CLPF with TNF (20 ng/mL) and IFN-gamma (10 ng/mL) for 3
      days reduced their migratory response to 10% of control (P < 0.001), which also
      was correlated with a decrease in FAK phosphorylation. Culture of IFN-gamma/TNF
      treated CLPF for a further 7 days without cytokines did not restore the migratory
      potential and FAK phosphorylation, indicating a persistent functional change.
      CONCLUSIONS: CD- and UC-CLPF have a reduced migratory potential compared with
      normal CLPF. That may be caused by contact with IFN-gamma and TNF. This loss of
      migratory potential was correlated with diminished FAK phosphorylation.

PMID- 14598251
TI  - Successful photodynamic therapy for nonresectable cholangiocarcinoma: a
      randomized prospective study.
AB  - BACKGROUND & AIMS: In nonrandomized trials, photodynamic therapy (PDT) had a
      promising effect on nonresectable cholangiocarcinoma (NCC). This prospective,
      open-label, randomized, multicenter study with a group sequential design compared
      PDT in addition to stenting (group A) with stenting alone (group B) in patients
      with NCC. METHODS: In patients with histologically confirmed cholangiocarcinoma,
      endoscopic or percutaneous double stenting was performed. Patients fulfilling
      inclusion criteria were randomized to group A (stenting and subsequent PDT) and
      group B (stenting alone). For PDT, Photofrin 2 mg/kg body wt was injected
      intravenously 2 days before intraluminal photoactivation (wavelength, 630 nm;
      light dose, 180 J/cm(2)). Further treatments were performed in cases of residual
      tumor in the bile duct. The primary outcome parameter was survival time.
      Secondary outcome parameters were cholestasis and quality of life. RESULTS: PDT
      resulted in prolongation of survival (group A: n = 20, median 493 days; group B:
      n = 19, median 98 days; P < 0.0001). It also improved biliary drainage and
      quality of life. CONCLUSIONS: PDT, given in addition to best supportive care,
      improves survival in patients with NCC. The study was terminated prematurely
      because PDT proved to be so superior to simple stenting treatment that further
      randomization was deemed unethical.

PMID- 14598252
TI  - Incidence, clinical spectrum, and outcomes of primary sclerosing cholangitis in a
      United States community.
AB  - BACKGROUND & AIMS: The epidemiology of primary sclerosing cholangitis (PSC) in
      the United States is unknown. We report the incidence, clinical spectrum, and
      outcomes of PSC in Olmsted County, Minnesota. METHODS: Using the Rochester
      Epidemiology Project, a medical records linkage system in Olmsted County,
      Minnesota, we identified county residents with PSC, and the diagnosis was
      confirmed according to clinical, biochemical, radiographic, and histologic
      criteria. RESULTS: Twenty-two patients met diagnostic criteria for PSC in 1976
      2000. The age-adjusted (to 2000 U.S. whites) incidence of PSC in men was 1.25 per
      100,000 person-years (95% CI, 0.70 to 2.06) compared with 0.54 per 100,000 person
      years (95% CI, 0.22 to 1.12) in women. The prevalence of PSC in 2000 was 20.9 per
      100,000 men (95% CI, 9.5 to 32.4) and only 6.3 per 100,000 women (95% CI, 0.1 to
      12.5). Seventy-three percent of cases had inflammatory bowel disease, the
      majority with ulcerative colitis. Survival among PSC patients was significantly
      less than expected for the Minnesota white population of similar age and gender
      (P < 0.001). CONCLUSIONS: These data represent the first population-based
      estimates of the incidence and prevalence of PSC in the United States. The
      incidence and prevalence of PSC were approximately one third of those previously
      described for primary biliary cirrhosis in the same population. Our data suggest
      that the prevalence of PSC in the United States, with its attendant medical
      burdens, is significantly greater than previously estimated.

PMID- 14598253
TI  - Sequence variation upstream of precore translation initiation codon reduces
      hepatitis B virus e antigen production.
AB  - BACKGROUND & AIMS: Most South African hepatitis B virus strains harbor point
      mutations immediately upstream of the precore AUG codon. The aim of this study
      was to determine their effect on hepatitis B e antigen expression. METHODS: The
      hepatitis B virus DNA sequence around the precore region was determined from sera
      of 45 black South Africans. The South African mutations were introduced into
      hepatitis B virus dimers of the same genotype, and hepatitis B e antigen was
      quantified from culture medium of transfected HepG2 or Huh7 cells. RESULTS: The
      South African sequence changes were easily detectable in the acute, hepatitis B e
      antigen-positive phase of infection, suggesting that they were stable traits and
      were not selected by immune pressure. Triple mutations at the -5, -3, and -2
      positions of the AUG codon severely impaired hepatitis B e antigen expression (P
      < 0.001). The frequent double mutation at the -5 and -2 positions moderately
      reduced hepatitis B e antigen levels (P < 0.001) to an extent comparable to that
      of the common core promoter mutations (1762(T)1764(A)). The presence of both
      South African and core promoter mutations diminished hepatitis B e antigen
      expression in an additive manner. It is interesting to note that the triple South
      African mutations enabled core protein translation from precore messenger RNA,
      which could rescue the replication defect of a hepatitis B virus genome with an
      ablated core gene. CONCLUSIONS: We have identified a novel class of hepatitis B e
      antigen variants with reduced hepatitis B e antigen translation by a ribosomal
      leaky scanning mechanism. Reduction in hepatitis B e antigen expression may
      contribute to accelerated seroconversion from hepatitis B e antigen to its
      antibody in black South Africans infected with hepatitis B virus very early in
      life.

PMID- 14598254
TI  - Distinct costimulation dependent and independent autoreactive T-cell clones in
      primary biliary cirrhosis.
AB  - BACKGROUND & AIMS: Previous work has suggested that CD4+ CD28- or costimulation
      independent T cells are increased in autoimmune diseases. In this study, we
      compared frequency and qualitative characteristics of autoreactive costimulation
      independent or CD4+ CD28- T cells in primary biliary cirrhosis (PBC) by taking
      advantage of the well-defined immunodominant autoepitope of the E2 component of
      pyruvate dehydrogenase (PDC-E2). METHODS: We determined the frequency of
      costimulation-independent autoreactive T cells that respond to PDC-E2 163-176 and
      the frequency of CD4+ CD28- T cells. Finally, we determined the role of biliary
      epithelial cells (BEC) as both an antigen-presenting cell or, alternatively, as a
      target cell for T-cell-mediated cytotoxicity. RESULTS: The precursor frequency of
      costimulation-independent CD4+ T cells that respond to PDC-E2 163-176 and the
      frequency of CD4+ CD28- T cells were dramatically elevated in PBC. Furthermore, 2
      types of T-cell clones that respond to PDC-E2 163-176 emerged from this study.
      One type was costimulation dependent and the other costimulation independent.
      Both types of clones lyse BEC in a similar effector target (E/T) ratio
      distribution. However, BEC did not help the proliferation of any T-cell clones.
      Furthermore, costimulation-independent T-cell clones do not become anergic by
      BEC. CONCLUSIONS: In PBC, costimulation-independent autoreactive T cells, which
      do not become anergic, increase and maintain the autoimmune response. In
      controls, although autoantigens are expressed on BEC and autoantigen-reactive T
      cells exist around BEC, autoantigen-reactive T cells are costimulation dependent
      and will become anergic and maintain peripheral tolerance.

PMID- 14598256
TI  - Purinergic mechanisms contribute to mechanosensory transduction in the rat
      colorectum.
AB  - BACKGROUND & AIMS: Adenosine 5'-triphosphate plays a role in peripheral sensory
      mechanisms and, in particular, mechanosensory transduction in the urinary system.
      P2X(3) receptors are selectively expressed on small-diameter sensory neurons in
      the dorsal root ganglia; sensory neurons from dorsal root ganglia L1 and S1
      supply the colorectum. This study investigated whether purinergic signaling
      contributes to mechanosensory transduction in the rat colorectum. METHODS: A
      novel in vitro rat colorectal preparation was used to elucidate whether adenosine
      5'-triphosphate is released from the mucosa in response to distention and to
      evaluate whether it contributes to sensory nerve discharge during distention.
      RESULTS: P2X(3) receptor immunostaining was present on subpopulations of neurons
      in L1 and S1 dorsal root ganglia, which supply the rat colorectum. Distention of
      the colorectum led to pressure-dependent increases in adenosine 5'-triphosphate
      release from colorectal epithelial cells and also evoked pelvic nerve excitation,
      which was mimicked by application of adenosine 5'-triphosphate and alpha,beta
      methylene adenosine 5'-triphosphate. The sensory nerve discharges evoked by
      distention were potentiated by alpha,beta-methylene adenosine 5'-triphosphate and
      ARL-67156, an adenosine triphosphatase inhibitor, and were attenuated by the
      selective P2X(1), P2X(3), and P2X(2/3) antagonist 2',3'-O-trinitrophenyl
      adenosine 5'-triphosphate and by the nonselective P2 antagonists pyridoxyl 5
      phosphate 6-azophenyl-2',4'-disulfonic acid and suramin. Adenosine, after
      ectoenzymatic breakdown of adenosine 5'-triphosphate, seems to be involved in the
      longer-lasting distention-evoked sensory discharge. Single-fiber analysis showed
      that high-threshold fibers were particularly affected by alpha,beta-methylene
      adenosine 5'-triphosphate, suggesting a correlation between purinergic activation
      and nociceptive stimuli. CONCLUSIONS: Adenosine 5'-triphosphate contributes to
      mechanosensory transduction in the rat colorectum, and this is probably
      associated with pain.

PMID- 14598255
TI  - Bacterial colonization leads to the colonic secretion of RELMbeta/FIZZ2, a novel
      goblet cell-specific protein.
AB  - BACKGROUND & AIMS: Goblet cells are highly polarized exocrine cells found
      throughout the small and large intestine that have a characteristic morphology
      due to the accumulation of apical secretory granules. These granules contain
      proteins that play important physiologic roles in cellular protection, barrier
      function, and proliferation. A limited number of intestinal goblet cell-specific
      proteins have been identified. In this study, we investigate the expression and
      regulation of RELMbeta, a novel colon-specific gene. METHODS: The regulation of
      RELMbeta messenger RNA expression was determined in LS174T, Caco-2, and HT-29
      cell lines in response to stimulation with interleukin 13 and lipopolysaccharide.
      Quantitative reverse-transcription polymerase chain reaction, immunoblots, and
      immunohistochemistry were used to examine the expression of RELMbeta in BALB/c
      and C.B17.SCID mice housed in conventional, germ-free, and gnotobiotic
      environments. RESULTS: Messenger RNA for RELMbeta is restricted to the
      undifferentiated, proliferating colonic epithelium. Immunohistochemistry shows
      that this protein is expressed in goblet cells located primarily in the distal
      half of the colon and cecum with lower levels detectable in the proximal colon.
      High levels of RELMbeta can be detected in the stool of mice and humans, where it
      exists as a homodimer under nonreducing conditions. Interestingly, the secretion
      of RELMbeta is dramatically reduced in germ-free mice. Furthermore, introduction
      of germ-free mice into a conventional environment results in enhanced expression
      and robust secretion of RELMbeta within 48 hours. CONCLUSIONS: These studies
      define a new goblet cell-specific protein and provide the first evidence that
      colon-specific gene expression can be regulated by colonization with normal
      enteric bacteria.

PMID- 14598257
TI  - Gastric inflammation triggers hypersensitivity to acid in awake rats.
AB  - BACKGROUND & AIMS: Changes in visceral sensation contribute to the development of
      dyspepsia. Nonhuman models have previously focused on responses to mechanical
      stimulation. We studied the response to acid stimulation in the normal and
      inflamed stomach in rats. METHODS: A balloon and gastrostomy catheter were
      implanted into the stomach. Electromyographic responses to gastric balloon
      distention or acid administration through the gastrostomy were recorded from the
      acromiotrapezius muscle. To characterize chemonociceptive pathways, 0.75 mL HCl
      (0.05-0.3 N) or saline were given intragastrically in controls and animals after
      vagotomy, splanchnic nerve resection, or chemical denervation with capsaicin. The
      effect of inflammation was examined after induction of mild diffuse gastritis
      using iodoacetamide or creating gastric ulcers by injecting 60% acetic acid for
      45 seconds into a clamped area of the stomach. RESULTS: Visceromotor
      electromyographic responses increased within 2 minutes after HCl administration
      (0.15 and 0.3 mol/L) but not saline or lower acid concentrations. Vagotomy and
      pretreatment with capsaicin but not splanchnic nerve resection abolished this
      response. Prior acid administration did not acutely sensitize animals to
      subsequent gastric distention. Gastritis and gastric ulcers enhanced the
      visceromotor responses to intragastric acid. CONCLUSIONS: In awake rats,
      visceromotor responses to intragastric acid are quantifiable, reliable, and
      reproducible. Aversive responses to acute noxious chemical stimuli primarily
      require vagal but not spinal sensory pathways. Injury-induced sensitization to
      intragastric acid administration is consistent with a potential role of chemical
      stimulation in triggering dyspeptic symptoms.

PMID- 14598258
TI  - Intratracheal IL-13 induces eosinophilic esophagitis by an IL-5, eotaxin-1, and
      STAT6-dependent mechanism.
AB  - BACKGROUND & AIMS: Eosinophil infiltration into the esophagus occurs in a wide
      range of diseases; however, the underlying pathophysiologic mechanisms involved
      are largely unknown. We have previously reported that simultaneous delivery of
      allergen to the lung and gastrointestinal tract induces experimental eosinophilic
      esophagitis (EE). We aimed to determine whether delivery of a Th2 cytokine
      (interleukin [IL]-13) to the lung was sufficient for induction of EE. METHODS: IL
      13 was delivered intratracheally to wild-type, signal transducer and activator of
      transcription (STAT) 6, eotaxin-1, or IL-5-deficient mice. Eosinophil levels and
      5'-bromodeoxyuridine (BrdU) incorporation were examined by immunohistochemical
      staining. RESULTS: Intratracheal delivery of IL-13 induced dose-dependent
      eosinophil accumulation in the esophagus (but not the stomach). In addition,
      intratracheal IL-13 induced esophageal epithelial hyperplasia. The ability of IL
      13 to induce EE was abolished in STAT6-deficient mice. IL-13-induced EE was
      nearly completely ablated in IL-5-deficient mice (37.3 +/- 11.6 vs. 3.3 +/- 3.2
      eosinophils/mm(2) in wild-type and IL-5-deficient mice, respectively).
      Additionally, IL-13-induced EE was significantly diminished in eotaxin-1
      deficient mice (48.7 +/- 10.3 vs. 14.1 +/- 12.5 eosinophils/mm(2) in wild-type
      and eotaxin-1-deficient mice, respectively). CONCLUSIONS: IL-13 delivery to the
      lung induces EE by an IL-5, eotaxin-1, and STAT6-dependent mechanism. These
      results further establish an intimate connection between respiratory and
      esophageal inflammation.

PMID- 14598259
TI  - Genetic background modifies intestinal pseudo-obstruction and the expression of a
      reporter gene in Hox11L1-/- mice.
AB  - BACKGROUND & AIMS: The transcription factor Hox11L1 is expressed by enteric
      neurons. Two groups mutated murine Hox11L1, and reported lethal intestinal pseudo
      obstruction and colonic hyperganglionosis in many, but not all, homozygous null
      mutants. We investigated the regulation of Hox11L1 and factors that influence the
      penetrance of pseudo-obstruction in Hox11L1-null mice. METHODS: Expression of
      beta-galactosidase (lacZ), under control of putative Hox11L1 regulatory
      sequences, was assessed in transgenic mice wild-type, heterozygous, and null for
      native Hox11L1. Transgene expression and signs of pseudo-obstruction were
      compared in null mice with different genetic backgrounds. RESULTS: In enteric
      neurons and other parts of the nervous system, the transgene was expressed in a
      pattern consistent with native Hox11L1. Enteric beta-galactosidase activity
      initiated in the proximal small intestine and spread cranially and caudally in a
      subset of postmitotic enteric neurons. Hox11L1-lacZ transgene expression
      persisted in Hox11L1-null animals, suggesting that Hox11L1 is not required cell
      autonomously for neuronal survival. Genetic background dramatically affected the
      phenotypes of Hox11L1-null animals, with complete penetrance of severe proximal
      colonic distention on a predominantly C57BL/6J (B6) background and very low
      penetrance of dysmotility on a 129SvJ (129) background. Coincidently, Hox11L1
      lacZ expression by most enteric neurons, but not CNS neurons, was lost on a 129
      background. CONCLUSIONS: Cis-acting, 5' regulatory elements are sufficient to
      regulate site-specific expression of Hox11L1 in vivo. Expression of the transgene
      by enteric neurons and penetrance of pseudo-obstruction in Hox11L1-null animals
      are influenced by one or more modifier genes, counterparts of which may play a
      similar role in human disease.

PMID- 14598260
TI  - Analysis of pulmonary heme oxygenase-1 and nitric oxide synthase alterations in
      experimental hepatopulmonary syndrome.
AB  - BACKGROUND & AIMS: Cirrhosis and portal hypertension due to chronic common bile
      duct ligation reproduce the features of human hepatopulmonary syndrome, whereas
      portal hypertension alone due to partial portal vein ligation does not. Nitric
      oxide contributes to experimental hepatopulmonary syndrome, but the nitric oxide
      synthase forms involved remain controversial. Recently, increased pulmonary heme
      oxygenase-1 expression and carbon monoxide production have also been found after
      common bile duct ligation. Our aim was to explore the role of the heme oxygenase
      1/carbon monoxide pathway in the pathogenesis of experimental hepatopulmonary
      syndrome. METHODS: Pulmonary heme oxygenase-1 expression and distribution were
      assessed in sham; 3-week partial portal vein ligation; and 1-, 2-, 3-, 4-, and 5
      week common bile duct ligation animals by Northern, Western and
      immunohistochemical analysis relative to endothelial and inducible nitric oxide
      synthase levels and to hepatopulmonary syndrome development. In vivo heme
      oxygenase enzyme inhibition with tin protoporphyrin IX in common bile duct
      ligation animals was used to define effects on intrapulmonary vasodilatation and
      arterial blood gases. RESULTS: Heme oxygenase-1 expression in pulmonary
      intravascular monocytes/macrophages and arterial carboxyhemoglobin levels
      increased progressively from 3 to 5 weeks after common bile duct ligation
      relative to controls (5-week protein levels were 15.94 +/- 1.75-fold those of
      sham animals; P < 0.001). Inducible nitric oxide synthase increased transiently
      in pulmonary intravascular monocytes/macrophages in 3-week common bile duct
      ligation animals, whereas pulmonary microvascular endothelial nitric oxide
      synthase increases began at 2 weeks and correlated with the onset of
      hepatopulmonary syndrome. Tin protoporphyrin treatment normalized
      carboxyhemoglobin and improved arterial blood gases and intrapulmonary
      vasodilatation, reflecting partial reversal of hepatopulmonary syndrome.
      CONCLUSIONS: The heme oxygenase-1/carbon monoxide system is an important
      contributor to the progression of experimental hepatopulmonary syndrome in
      addition to alterations in the endothelial nitric oxide synthase/nitric oxide
      pathway.

PMID- 14598261
TI  - Mesenteric vasoconstriction triggers nitric oxide overproduction in the superior
      mesenteric artery of portal hypertensive rats.
AB  - BACKGROUND & AIMS: Vasoconstriction of the superior mesenteric artery (SMA) is
      the earliest hemodynamic event occurring after partial portal vein ligation
      (PVL). We tested the hypothesis that this early vasoconstriction of the SMA may
      initiate eNOS up-regulation in PVL. METHODS: Portal hypertension with or without
      mesenteric vasoconstriction was induced by differentially calibrated stenosis of
      the portal vein (PVL-20G and PVL-18G, respectively). In a separate group of rats,
      mesenteric vasoconstriction was achieved by renal artery ligation. Sham-operated
      rats were used as controls. Effects of vasoconstriction of the SMA in PVL and RAL
      rats were evaluated by measuring perfusion pressure changes in isolated SMA beds
      in response to methoxamine, nitric oxide synthase activity, and eNOS protein
      expression. Mean arterial pressure, portal pressure, and SMA blood flow were
      measured by catheterization and Doppler flowmetry. SMA vascular resistance was
      calculated from arterial pressure, portal pressure, and SMA flow. RESULTS: There
      was a significant increase in SMA vascular resistance in PVL-20G (2.33 +/- 0.13
      vs. 1.22 +/- 0.03 mm Hg/% flow; P < 0.05) and RAL (2.32 +/- 0.18 vs. 1.18 +/-
      0.02 mm Hg/% flow; P < 0.05) but not in PVL-18G, showing mesenteric
      vasoconstriction in both PVL-20G and RAL groups. The mesenteric vasculature of
      PVL-20G and RAL animals showed hyporeactivity to methoxamine (P < 0.01). Whereas
      both PVL groups were portal hypertensive (P < 0.01), RAL rats were not. The SMA
      hyporeactivity of PVL-20G and RAL rats was corrected by N(G)()-monomethyl-L
      arginine, and nitric oxide synthase enzyme activity was significantly higher in
      PVL-20G and RAL rats (P < 0.05). CONCLUSIONS: Mesenteric arterial
      vasoconstriction plays a triggering role in up-regulation of eNOS catalytic
      activity in the SMA of portal hypertensive rats.

PMID- 14598262
TI  - Gastric fundic gland polyps.

PMID- 14598263
TI  - Familial liver adenomatosis associated with hepatocyte nuclear factor 1alpha
      inactivation.
AB  - BACKGROUND & AIMS: Germline mutations in hepatocyte nuclear factor 1alpha
      (TCF1/HNF-1alpha) are associated with maturity-onset diabetes of the young type 3
      (MODY3), and somatic biallelic inactivations of the gene are found in
      hepatocellular adenomas and liver adenomatosis. This study investigated
      cosegregation of HNF-1alpha germline mutations with diabetes and liver
      adenomatosis in 2 families. METHODS: Two unrelated patients with liver
      adenomatosis and harboring HNF-1alpha germline and somatic mutations were
      studied. Subsequently, we screened 9 relatives in the 2 independent families for
      diabetes, hepatocellular adenomas, and HNF-1alpha germline mutations. RESULTS: In
      family A, a father and his son presented with an intraperitoneal hemorrhagic
      rupture of a liver adenomatosis without diabetes. A heterozygous R229X germline
      mutation was identified in HNF-1alpha in the father and his son and also in his
      second 27-year-old son without hepatocellular adenomas. In family B, a diagnosis
      of liver adenomatosis was made fortuitously in a 14-year-old girl. A heterozygous
      G55fsX57 germline mutation in HNF-1alpha was identified in this patient, her
      diabetic father, and her 2 sisters. Systematic exploration showed liver
      adenomatosis in the 2 sisters. Somatic inactivation of the second HNF-1alpha
      allele was found in liver tumors in both families. CONCLUSIONS: This study
      describes familial liver adenomatosis and shows the association with germline HNF
      1alpha mutations in adults and children. It also highlights the importance of
      screening for hepatocellular adenomas, diabetes, and HNF-1alpha germline
      mutations in relatives of patients with liver adenomatosis. Finally, prevalence
      of liver adenomatosis remains to be evaluated in MODY3 subjects.

PMID- 14598265
TI  - Recent insights on the mechanisms of liver preconditioning.
AB  - Ischemia/reperfusion is the main cause of hepatic damage consequent to temporary
      clamping of the hepatoduodenal ligament during liver surgery as well as graft
      failure after liver transplantation. In recent years, a number of animal studies
      have shown that pre-exposure of the liver to transient ischemia, hyperthermia, or
      mild oxidative stress increases the tolerance to reperfusion injury, a phenomenon
      known as hepatic preconditioning. The development of hepatic preconditioning can
      be differentiated into 2 phases. An immediate phase (early preconditioning)
      occurs within minutes and involves the direct modulation of energy supplies, pH
      regulation, Na(+) and Ca(2+) homeostasis, and caspase activation. The subsequent
      phase (late preconditioning) begins 12-24 hours after the stimulus and requires
      the synthesis of multiple stress-response proteins, including heat shock proteins
      HSP70, HSP27, and HSP32/heme oxygenase 1. Hepatic preconditioning is not limited
      to parenchymal cells but ameliorates sinusoidal perfusion, prevents postischemic
      neutrophil infiltration, and decreases the production of proinflammatory
      cytokines by Kupffer cells. This latter effect is important in improving systemic
      disorders associated with hepatic ischemia/reperfusion. The signals triggering
      hepatic preconditioning have been partially characterized, showing that
      adenosine, nitric oxide, and reactive oxygen species can activate multiple
      protein kinase cascades involving, among others, protein kinase C and p38 mitogen
      activated protein kinase. These observations, along with preliminary studies in
      humans, give a rationale to perform clinical trials aimed at verifying the
      possible application of hepatic preconditioning in preventing
      ischemia/reperfusion injury during liver surgery.

PMID- 14598264
TI  - Pediatric-onset primary biliary cirrhosis.
AB  - Unlike other autoimmune liver diseases, primary biliary cirrhosis (PBC) has not
      been reported in childhood. We report 2 cases of PBC diagnosed at 16 and 15 years
      of age, respectively. The first girl was noted to have increased liver enzyme
      levels at 16 years of age. Antimitochondrial antibody (AMA) was strongly
      positive, and serum quantitative immunoglobulin M level was 8.26 g/L (normal, 0.6
      3 g/L). A liver biopsy specimen showed stage II PBC. Despite treatment with
      ursodeoxycholic acid, she developed progressive cholestasis, intractable
      pruritus, and a significant sensory neuropathy and weight loss eventually
      requiring liver transplantation. Her mother had PBC/autoimmune overlap syndrome
      and underwent successful liver transplantation at 34 years of age. The second
      girl had persistently elevated liver enzyme levels following cholecystectomy at
      15 years of age for symptomatic cholelithiasis. Endoscopic retrograde
      cholangiopancreatography showed no abnormalities. AMA was positive at 1:160, and
      serum quantitative immunoglobulin was 6.96 g/L. A liver biopsy specimen showed
      stage II PBC, and her liver enzyme levels almost normalized after starting
      treatment with ursodeoxycholic acid. In conclusion, we present 2 liver biopsy
      confirmed cases of pediatric-onset AMA-positive PBC. With increased awareness of
      early-onset PBC, further pediatric cases may be discovered.

PMID- 14598266
TI  - Ghrelin for the gastroenterologist: history and potential.
AB  - Ghrelin, a novel 28-amino acid orexigenic peptide discovered in 1999, has given
      us further insights into the control of energy homeostasis and growth hormone
      secretion. As a natural endogenous ligand of the growth hormone secretagogue
      receptor, it potently stimulates growth hormone release but is also implicated in
      many other homeostatic mechanisms. Released from the stomach, it stimulates
      lactotroph and corticotroph secretion, increases appetite and adiposity, has
      beneficial hemodynamic effects, has prokinetic and gastric acid secretory
      functions in the stomach, and may even be implicated in sleep. As advances in the
      understanding of appetite and obesity are made, it is timely to review the
      possibly central role of ghrelin in these physiological and pathophysiological
      states. This review will discuss the recent literature concerning this exciting
      novel neuropeptide and discuss the possible therapeutic possibilities it may open
      up to us.

PMID- 14598267
TI  - American Gastroenterological Association medical position statement: perianal
      Crohn's disease.

PMID- 14598268
TI  - AGA technical review on perianal Crohn's disease.

PMID- 14598269
TI  - The many faces of low-grade dysplasia.

PMID- 14598270
TI  - Biofeedback for fecal incontinence.

PMID- 14598272
TI  - Aspirin and the prevention of colorectal neoplasia.

PMID- 14598271
TI  - A spotlight on cholangiocarcinoma.

PMID- 14598273
TI  - The genetics of Shwachman-Diamond syndrome.

PMID- 14598274
TI  - Confined treatment.

PMID- 14598275
TI  - Influence of immunogenicity on the long-term efficacy of infliximab in Crohn's
      disease.

PMID- 14598276
TI  - Increasing the RISC for HCV.

PMID- 14598291
TI  - Myelin-associated inhibitors of axon regeneration.
AB  - Trauma in the adult mammalian central nervous system (CNS) has devastating
      clinical consequences due to the failure of injured axons to spontaneously
      regenerate. Over 20 years ago, pioneering work demonstrated that the non
      permissive nature of CNS myelin for axon outgrowth contributes to this
      regenerative failure. Over the past few years, tremendous progress has been made
      in our understanding of the inhibitory components of CNS myelin, the axonal
      receptors that respond to these cues, and the intracellular signaling cascades
      mediating axon outgrowth inhibition. Several approaches designed to antagonize
      molecular mediators of axon inhibition have been tested in an effort to promote
      regenerative growth after CNS injury. These studies have validated the role of
      many candidate proteins in axon outgrowth inhibition; however, other approaches
      such as the generation of knockout mice for myelin-associated inhibitors have
      created new questions in the field.

PMID- 14598292
TI  - Specific inhibitor of FGF receptor signaling: FGF-2-mediated effects on
      proliferation, differentiation, and MAPK activation are inhibited by PD173074 in
      oligodendrocyte-lineage cells.
AB  - Multiple studies have shown that migration, proliferation, and differentiation of
      oligodendrocyte (OL) lineage cells are influenced by fibroblast growth factor-2
      (FGF-2) signaling through its receptors (FGFR) FGFR-1, FGFR-2, and FGFR-3. We
      report the effectiveness and specificity of a unique inhibitor, PD173074, for
      inhibiting FGF receptor signaling in OL-lineage cells. Three FGF-mediated
      responses of OL progenitors and two of differentiated OLs were examined by
      immunofluorescence microscopy and immunoblotting. PD173074 effectively
      antagonized the effect of FGF-2 on proliferation and differentiation of OL
      progenitors in culture. One dose of PD173074 at nanomolar concentrations was
      sufficient to inhibit ongoing FGF-2 mediated proliferation for prolonged periods,
      in a non-toxic, dose-dependent manner. In contrast, platelet-derived growth
      factor (PDGF)-induced proliferation was unaffected by PD173074. Similarly,
      mitogen-activated protein kinase (MAPK) activation, a downstream event after
      activation of either FGFR or PDGFR, was also blocked by PD173074 in OL
      progenitors stimulated with FGF-2 but not PDGF. A general tyrosine kinase
      inhibitor (PD166285), however, antagonized both FGF-2- and PDGF-mediated
      responses. PD173074 also completely antagonized two phenotypic alterations of
      differentiated OLs, specifically downregulation of myelin proteins, and their re
      entry into the cell cycle. We conclude that PD173704 is an effective and specific
      inhibitor for multiple FGF-2-mediated responses of both OL progenitors and
      differentiated OLs. This inhibitor provides a direct approach for identifying the
      importance of FGF signaling, comparable in effect to a knockout of all FGF
      receptors and all FGF ligands, while leaving other pathways unaffected. Thus,
      PD173704 is an excellent tool for investigating the role of FGF signaling in vivo
      in the context of combinatorial interactions of other signals.

PMID- 14598293
TI  - Phosphoinositide 3-kinase promotes adult subventricular neuroblast migration
      after stroke.
AB  - Rodent adult subventricular zone (SVZ)-derived progenitor cells abandon the
      rostral migratory stream (RMS)/olfactory complex postmiddle cerebral artery
      occlusion (MCAo) and migrate into compromised tissue, possibly playing a role in
      brain recovery. Using SVZ tissue explants from the adult rat, we investigated the
      role of the phosphoinositide 3-kinase (PI3K) signal transduction pathway in the
      migration of SVZ cells. Stroke significantly (P <.01) increased migratory speed
      (198 +/- 39 microm/day) of neuroblasts out of the SVZ explants compared with the
      speed (99 +/- 20 microm/day) in the normal SVZ (nSVZ) explants within the first 3
      days of incubation. Three-dimensional laser scanning confocal microscopy revealed
      formation of neuroblast encompassing chain-like astrocyte structures extruding
      from both normal and stroke explants. Western blots showed that stroke SVZ (sSVZ)
      explants increased Akt phosphorylation. Treatment of sSVZ explants with the
      selective PI3K inhibitor LY294002 significantly (P <.01) attenuated neuroblast
      migration and Akt phosphorylation, whereas treatment with LY294002 did not affect
      the number of bromodeoxyuridine (BrdU)- and caspase-3-immunoreactive cells,
      indicating that stroke-enhanced neuroblast migration is independent of cell
      proliferation and survival. PI3K catalyzes phosphatidylinositol-3,4,5
      triphosphate (PIP(3)) which facilitates Akt phosphorylation. Thus, our data
      demonstrate that the PI3K/Akt signal transduction pathway mediates neuroblast
      migration after stroke.

PMID- 14598294
TI  - Treatment of chronically injured spinal cord with neurotrophic factors stimulates
      betaII-tubulin and GAP-43 expression in rubrospinal tract neurons.
AB  - Exogenous neurotrophic factors provided at a spinal cord injury site promote
      regeneration of chronically injured rubrospinal tract (RST) neurons into a
      peripheral nerve graft. The present study tested whether the response to
      neurotrophins is associated with changes in the expression of two regeneration
      associated genes, betaII-tubulin and growth-associated protein (GAP)-43. Adult
      female rats were subjected to a right full hemisection lesion via aspiration of
      the C3 spinal cord. A second aspiration lesion was made 4 weeks later and gel
      foam saturated in brain-derived neurotrophic factor (BDNF), glial cell-line
      derived neurotrophic factor (GDNF), or phosphate-buffered saline (PBS) was
      applied to the lesion site for 60 min. Using in situ hybridization, RST neurons
      were examined for changes in mRNA levels of betaII-tubulin and GAP-43 at 1, 3,
      and 7 days after treatment. Based on analysis of gene expression in single cells,
      there was no effect of BDNF treatment on either betaII-tubulin or GAP-43 mRNA
      expression at any time point. betaII-Tubulin mRNA levels were enhanced
      significantly at 1 and 3 days in animals treated with GDNF relative to levels in
      animals treated with PBS. Treatment with GDNF did not affect GAP-43 mRNA levels
      at 1 and 3 days, but at 7 days there was a significant increase in mRNA
      expression. Interestingly, 7 days after GDNF treatment, the mean cell size of
      chronically injured RST neurons was increased significantly. Although GDNF and
      BDNF both promote axonal regeneration by chronically injured neurons, only GDNF
      treatment is associated with upregulation of betaII-tubulin or GAP-43 mRNA. It is
      not clear from the present study how exogenous BDNF stimulates regrowth of
      injured axons.

PMID- 14598295
TI  - Systemic insulin-like growth factor-I administration prevents cognitive
      impairment in diabetic rats, and brain IGF regulates learning/memory in normal
      adult rats.
AB  - Diabetic patients have impaired learning/memory, brain atrophy, and two-fold
      increased risk of dementia. The cause of cognitive disturbances that progress to
      dementia is unknown. Because neurotrophic insulin-like growth factor (IGF) levels
      are reduced in diabetic patients and rodents, and IGF can cross the blood-central
      nervous system barrier (B-CNS-B), the hypothesis was tested that IGF administered
      systemically can prevent cognitive disturbances, independently of hyperglycemia
      and a generalized catabolic state. Latency to escape to a hidden platform in the
      Morris Water Maze is used widely to test spatial memory, a hippocampus-dependent
      task. Adult rats were rendered diabetic with streptozotocin and implanted 4 weeks
      later with subcutaneous pumps that released either vehicle (D + Veh) or 20
      microg/day IGF-I (D + IGF). Latency to escape to the hidden platform was
      prolonged in (D + Veh) versus non-diabetic rats (P < 0.003) 10.5 weeks after the
      onset of diabetes. Such prolongation was prevented in (D + IGF) versus (D + Veh)
      rats (P < 0.03). The data show that IGF-I can act across the B-CNS-B to prevent
      loss of cognition-related performance in the water maze independently of ongoing
      hyperglycemia and reduction in brain (P < 0.001) and whole body weight (P <
      0.001) in diabetic rats. The hypothesis that brain IGF contributes to
      learning/memory was tested. An anti-IGF antibody, or preimmune serum, was infused
      into the lateral ventricles in non-diabetic rats. Learning in a passive avoidance
      task was impaired significantly in the IGF antibody versus preimmune serum
      treated groups on test Days 1, 2, and 3 (P = 0.04, 0.02 and 0.004, respectively).
      The data together are consistent with a model in which brain IGF is essential for
      learning/memory, and a loss of IGF activity due to diabetes may contribute to
      cognitive disturbances.

PMID- 14598296
TI  - Effects of immunosuppression on regrowth of adult rat retinal ganglion cell axons
      into peripheral nerve allografts.
AB  - Analysis of the effectiveness of allografts and immunosuppression in the repair
      of nerve defects in the adult peripheral nervous system (PNS) has a long
      experimental and clinical history. There is little information, however, on the
      use of allografts in peripheral nerve (PN) transplantation into the injured
      central nervous system (CNS). We assessed the ability of PN allografts (from Dark
      Agouti rats) to support regeneration of adult rat retinal ganglion cell (RGC)
      axons in immunosuppressed host Lewis rats. PN allografts were sutured onto
      intraorbitally transected optic nerves. Three weeks after grafting, regenerating
      RGC axon numbers were determined using retrograde fluorescent labelling, and
      total axons within PN grafts were assessed using pan-neurofilament
      immunohistochemistry. In the absence of immunosuppression, PN allografts
      contained few axons and there were very few labelled RGC. These degenerate grafts
      contained many T cells and macrophages. Systemic (intraperitoneal) application of
      the immunosuppressants cyclosporin-A or FK506 reduced cellular infiltration into
      allografts and resulted in extensive axonal regrowth from surviving RGCs. The
      average number of RGCs regenerating axons into immunosuppressed allografts was
      not significantly different from that seen in PN autografts in rats sham-injected
      with saline. Many pan-neurofilament-positive axons, a proportion of which were
      myelinated, were seen in immunosuppressed allografts, particularly in proximal
      regions of the grafts toward the optic nerve-PN interface. This study
      demonstrates that PN allografts can support axonal regrowth in immunosuppressed
      adult hosts, and points to possible clinical use in CNS repair.

PMID- 14598297
TI  - Isolation of neural stem cells from the forebrain of deceased early postnatal and
      adult rats with protracted post-mortem intervals.
AB  - Neural stem cells were isolated from deceased early postnatal and adult rats with
      varying post-mortem intervals. Animals were killed by deep anesthesia and stored
      in a refrigerator at 4 degrees C for 1-6 days before use. Neurospheres were
      obtained from the forebrain tissue, including the lateral ventricle in the early
      postnatal rats, and from the striatal wall of lateral ventricle, including the
      subventricular zone (SVZ) in adult rats. The number of neurospheres obtained in
      the primary culture from early postnatal animals was much larger than that from
      the adult rats. There was no significant difference in the population of
      neurospheres between the living and the deceased animals at least within 2 days
      after death. A few neurospheres were still obtainable at 6 days after death in
      early postnatal animals, but almost no neurospheres were obtained at 5 days after
      death in the adult rats. The differentiation capacity of neural stem cells in
      neurospheres was similar between the deceased and the living animals. The rich
      vascular bed in the SVZ of the lateral ventricle suggests that the vascular
      architecture might be in part responsible for the survival of the neural stem
      cells in the deceased animals. Neurosphere cells derived from deceased adult rats
      survived and differentiated mainly into glial cells in the host spinal cord
      tissue after transplantation into the injured spinal cord. Therefore, the neural
      stem cells from deceased animals express the same phenotypes as those from living
      animals in terms of neurosphere formation, proliferation, and differentiation at
      least 2 days after death. The neural stem cells from cadavers have great
      significance in terms of their clinical use as homografts for CNS regeneration.

PMID- 14598299
TI  - Changes in spinal GDNF, BDNF, and NT-3 expression after transient spinal cord
      ischemia in the rat.
AB  - Previous studies have demonstrated that the expression of several growth factors
      including glial cell-derived neurotrophic factor (GDNF), brain-derived growth
      factor (BDNF), and neurotrophin-3 (NT-3) play an important role in defining
      neuronal survival after brain ischemia. In the present study, using a well
      defined model of transient spinal ischemia in rat, we characterized the changes
      in spinal GDNF, BDNF, and NT-3 expression as defined by enzyme-linked
      immunosorbent assay (ELISA) and immunofluorescence coupled with deconvolution
      microscopy. In control animals, baseline levels of GDNF, BDNF, and NT-3 (74 +/-
      22, 3,600 +/- 270, 593 +/- 176 pg/g tissue, respectively) were measured. In the
      ischemic group, 6 min of spinal ischemia resulted in a biphasic response with
      increases in tissue GDNF and BDNF concentrations at the 2-hr and 72-hr points
      after ischemia. No significant differences in NT-3 concentration were detected.
      Deconvolution analysis revealed that the initial increase in tissue GDNF
      concentration corresponded to a neuronal upregulation whereas the late peak seen
      at 72 hr corresponded with increased astrocyte-derived GDNF synthesis. Increased
      expression of BDNF was seen in neurons, astrocytes, and oligodendrocytes. These
      data suggest that the early increase in neuronal GDNF/BDNF expression likely
      modulates neuronal resistance/recovery during the initial period of postischemic
      reflow. Increased astrocyte-derived BDNF/GDNF expression corresponds with
      transient activation of astrocytes and may play an active role in neuronal
      plasticity after non-injurious intervals of spinal ischemia.

PMID- 14598298
TI  - Plasmalemmal sealing of transected mammalian neurites is a gradual process
      mediated by Ca(2+)-regulated proteins.
AB  - Cultured mammalian PC12 or B104 cells do not instantaneously restore a
      plasmalemmal barrier (seal) after neurite transection, as measured using
      fluorescent dye probes of various sizes and saline solutions with different
      [Ca(2+)](o). Rather, transected cells gradually (from 15 to 60 min postseverance)
      exclude probes (dye molecules) of progressively smaller size. Furthermore, an
      inhibitor (calpeptin) of a Ca(2+)-activated cysteine protease (calpain) and
      antibodies or toxins to a Ca(2+)-regulated protein (synaptotagmin) and other
      membrane fusion proteins (syntaxin and synaptobrevin) inhibit plasmalemmal
      sealing. These data obtained using molecular probes on mammalian cell lines are
      consistent with previous data on invertebrate giant axons indicating that Ca(2+)
      plays many roles in the formation, accumulation, and fusion/interaction of
      vesicles gradually forming a seal at a site of plasmalemmal damage.

PMID- 14598300
TI  - Identifying loci for behavioral traits using genome-tagged mice.
AB  - Identification of behavioral loci through complex trait mapping remains a widely
      employed approach but suffers from poor gene localization and low replicability.
      Genome-tagged mice (GTMs) are overlapping sets of congenic strains spanning the
      whole genome and offer the possibilities of superior mapping power and
      reproducibility. In this study, three GTM strains each consisting of an average
      approximately 27 cM DBA/2J genomic intervals introgressed onto a C57BL/6J
      background were employed for localization of behavioral traits. These GTMs were
      chosen because the corresponding chromosomal regions had been previously
      identified as containing loci for learning and memory. Analysis of the GTMs
      allowed confirmation of the learning and memory loci, and one on chromosome 3 was
      in addition fine mapped to an 8.8-cM region of overlap between two of the GTMs.
      Moreover, loci for prepulse inhibition of the startle response, acoustic startle
      response, and spontaneous locomotor activity were also mapped. These results
      suggest that the GTMs should be a valuable resource for mapping and confirmation
      of loci contributing to complex behavioral traits in the mouse.

PMID- 14598301
TI  - Consolidation of memory for odour-reward association requires transient
      polysialylation of the neural cell adhesion molecule in the rat hippocampal
      dentate gyrus.
AB  - Cell adhesion molecule function is involved in hippocampal synaptic plasticity
      and is associated with memory consolidation. At the infragranular zone of the
      dentate gyrus, neurons expressing the polysialylated form of the neural cell
      adhesion molecule (NCAM PSA) transiently increase their frequency at the 12-hr
      posttraining time in behaviours elicited by stressful stimuli, such as those
      associated with conditioned avoidance, water maze, and fear conditioning
      paradigms. To determine whether learning-induced modulation of NCAM
      polysialylation is limited to stressful paradigms, we employed a reward-based
      odour discrimination task. Animals show a rapid acquisition and recall of this
      task in terms of latency to identify the food-associated odour and the number of
      choice errors. Immunohistochemical procedures were employed to determine the
      change in NCAM PSA expression following task acquisition. NCAM PSA
      immunoreactivity in the hippocampal formation was most intense on the granule
      like neurons in the infragranular zone of the dentate gyrus, and their frequency
      transiently increased in the 12-hr posttraining period. The nature of the
      transient increase in NCAM PSA-immunoreactive neurons was indistinguishable from
      that observed following avoidance conditioning or spatial learning, in that it
      occurred at the same time. The transient increase in NCAM PSA expression is
      suggested to facilitate dendritic elaboration in response to the acquisition of
      novel behavioural repertoires.

PMID- 14598302
TI  - Ethanol-induced oxidative stress precedes mitochondrially mediated apoptotic
      death of cultured fetal cortical neurons.
AB  - In utero ethanol exposure elicits apoptotic cell death in the fetal brain, and
      this may be mediated by oxidative stress. Our studies utilize cultured fetal rat
      cortical neurons and illustrate that ethanol elicits a rapid onset of oxidative
      stress, which culminates in mitochondrially mediated apoptotic cell death. Cells
      exposed to ethanol (2.5 mg/ml) remained attached to their polylysine matrix
      during a 24-hr exposure, but they exhibited distinct signs of oxidative stress,
      decreased viability, and apoptosis. Confocal microscopy of live cortical neurons
      pretreated with dichlorodihydrofluorescein diacetate demonstrated an increase in
      reactive oxygen species (ROS) within 5 min of ethanol exposure. The levels of ROS
      further increased by 58% within 1 hr (P <.05) and by 82% within 2 hr (P <.05),
      accompanied by increases of mitochondrial 4-hydroxynonenal (HNE). These early
      events were followed by decreased trypan blue exclusion of 10% to 32% (P <.05) at
      the 6- to 24-hr time points, respectively. This culminates in apoptotic death,
      with increases of Annexin V binding of 43%, 89%, 123%, and 238%, at 2, 6, 12, and
      24 hr of ethanol treatment, respectively, as well as DNA fragmentation increases
      of 50% and 65% by 12 and 24 hr, respectively. Release of cytochrome c by
      mitochondria increased by 53% at 6 hr of exposure (P <.05), concomitant with
      activation of caspase 3 (52% at 12 hr, P <.05). Pretreatment with N
      acetylcysteine increased cellular glutathione and prevented apoptosis. These
      studies provide a time line illustrating that oxidative stress and formation of a
      proapoptotic lipid peroxidation product, HNE, precede a cascade of
      mitochondrially mediated events in cultured fetal cortical neurons, culminating
      in apoptotic death. The prevention of apoptosis by augmentation of glutathione
      stores also strongly supports a role for oxidative stress in ethanol-mediated
      apoptotic death of fetal cortical neurons.

PMID- 14598303
TI  - An inhibitor of mitochondrial complex I, rotenone, inactivates proteasome by
      oxidative modification and induces aggregation of oxidized proteins in SH-SY5Y
      cells.
AB  - In Parkinson's disease, characteristic pathological features are the cell death
      of nigrostriatal dopamine neurons and the formation of Lewy bodies composed of
      oxidized proteins. Mitochondrial dysfunction and aggregation of abnormal proteins
      have been proposed to cause the pathological changes. However, the relation
      between these two factors remains to be clarified. In this study, the effects of
      mitochondrial dysfunction on the oxidative modification and accumulation of
      proteins were analyzed using an inhibitor of mitochondrial complex I, rotenone,
      and antibodies against acrolein- and dityrosine-modified proteins. Under
      conditions inducing mainly apoptosis in neuroblastoma SH-SY5Y cells, rotenone
      markedly increased oxidized proteins, especially those modified with acrolein,
      even though the increase in intracellular reactive oxygen and nitrogen species
      was only transient and was not so marked. In addition, the activity of the
      proteasome system degrading oxidized proteins was reduced profoundly after
      treatment with rotenone. The 20S beta subunit of proteasome was modified with
      acrolein, to which other acrolein-modified proteins were found to bind, as shown
      by coprecipitation with the antibody against 20S beta subunit. These results
      suggest that mitochondrial dysfunction, especially decreased activity of complex
      I, may reduce proteasome activity through oxidative modification of proteasome
      itself and aggregation with other oxidized proteins. This mechanism might account
      for the accumulation of modified protein and, at least partially, for cell death
      of the dopamine neurons in Parkinson's disease.

PMID- 14598305
TI  - Opposing effects of low and high-dose clozapine on survival of transgenic
      amyotrophic lateral sclerosis mice.
AB  - Clozapine is a potent atypical neuroleptic or antipsychotic agent used to relieve
      symptoms of early-diagnosed schizophrenia. Aside from well-described dopamine and
      serotonin receptor blockade effects, clozapine may also be neuroprotective
      through its modulation of the p75 neurotrophin receptor (p75(NTR)) and superoxide
      dismutase 1 (SOD1) expression. The death-signalling activities of both p75(NTR)
      and mutant SOD1 are implicated in motor neuron degeneration in humans and
      transgenic mice with amyotrophic lateral sclerosis (ALS). We therefore
      investigated the effects of clozapine in cell culture and mouse models of ALS.
      Clozapine dose-dependently inhibited full-length and cleaved p75(NTR) but not
      SOD1 protein expression in the motor neuron-like (NSC-34) cell line. Furthermore,
      low concentrations of clozapine protected NSC-34 cells from paraquat-mediated
      superoxide toxicity, nerve growth factor (NGF)-induced death signalling, and
      serum deprivation, whereas high concentrations potentiated death. Systemic thrice
      weekly administration of low and high-dose clozapine to mutant superoxide
      dismutase 1 (SOD1(G93A)) mice produced differential effects on disease onset and
      survival. Low-dose treatment was associated with delayed locomotor impairment and
      death, compared to high-dose clozapine, which accelerated paralysis and mortality
      (P < 0.05). Increased death was not attributable to toxicity, as clozapine
      induced agranulocytosis was not detected from blood analysis. High-dose
      clozapine, however, produced extrapyramidal symptoms in mice manifest by hindlimb
      rigidity, despite reducing spinal cord p75(NTR) levels overall. These results
      suggest that although clozapine may exert p75(NTR)-mediated neuroprotective
      activity in vitro, its profound antagonistic effects on dopaminergic and
      serotonergic systems in vivo at high doses may exacerbate the phenotype of
      transgenic ALS mice.

PMID- 14598304
TI  - Nonopioid receptor-mediated effects of U-50,488H on [Ca(2+)]i and extracellular
      dopamine in PC12 cells.
AB  - The present studies were carried out to determine the effects of a kappa-opioid
      receptor agonist on cytosolic Ca(2+) concentration, [Ca(2+)](i), and
      extracellular dopamine in undifferentiated PC12 cells. The kappa-opioid receptor
      agonist U-50,488H caused concentration-dependent increases in [Ca(2+)](i) and
      extracellular dopamine. Neither effect was blocked by the selective kappa-opioid
      receptor antagonist nor-binaltorphimine. Increases in extracellular dopamine
      content and [Ca(2+)](i) caused by U-50,488H were correlated positively in the
      presence of extracellular Ca(2+); however, reduction of extracellular Ca(2+)
      abolished the increase in [Ca(2+)](i), but not that in dopamine. The latter
      observation suggests that stimulation of exocytotic release is not the primary
      mechanism involved in the increase in extracellular dopamine caused by U-50,488H.
      Effects on dopamine synthesis or catabolism also seem unlikely because the
      enhancement of extracellular dopamine occurred rapidly, and the amount of a major
      metabolite of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), was not affected.
      In any event, neither the increase in [Ca(2+)](i) nor the increase in
      extracellular dopamine caused by U-50,488H is mediated by the kappa-opioid
      receptor.

PMID- 14598307
TI  - Plastic changes of calcitonin gene-related peptide in morphine tolerance:
      behavioral and immunohistochemical study in rats.
AB  - The present study was undertaken to investigate the plasticity of calcitonin gene
      related peptide (CGRP) in antinociception after morphine tolerance in rats. The
      hindpaw withdrawal latencies (HWLs) to both thermal and mechanical stimulation
      increased significantly after intracerebroventricular injection of 2.5 nmol of
      CGRP in opioid-naive rats, indicating that CGRP produces an antinociceptive
      effect in the brain. Furthermore, there was an antinociceptive effect after
      intracerebroventricular injection of 2.5 nmol of CGRP in morphine-tolerant rats.
      Interestingly, the antinociceptive effect induced by intracerebroventricular
      injection of CGRP was lower in morphine-tolerant rats than that in opioid-naive
      rats at the same dose. At the same time, there was downregulation of CGRP-like
      immunoreactivity in both lateral septal nucleus and central nucleus of amygdala
      tested by immunohistochemical methods, whereas no significant changes were
      observed in arcuate nucleus of hypothalamus and periaqueductal gray after
      morphine treatment in rats. The present study demonstrates plastic changes in
      both CGRP-induced antinociception and CGRP-like immunoreactivity in rat brain
      after morphine tolerance, suggesting that CGRP may play an important role in
      morphine tolerance.

PMID- 14598306
TI  - Decrease of morphine-induced reward effects and withdrawal symptoms in mice
      overexpressing gamma-aminobutyric acid transporter I.
AB  - Morphine addiction has been shown to result from neural adaptations produced by
      repeated drug exposure, but the mechanism is still unclear. In the present study,
      we found that gamma-aminobutyric acid (GABA) uptake was increased in mouse brain
      120 min after, but not 20 min after, morphine (10 mg/kg, s.c.) injection. We
      generated GABA transporter I (GAT1)-overexpressing mice to investigate whether
      the GABAergic system and GABA transporter are involved in morphine-induced reward
      effects and withdrawal symptoms. Our results revealed that the rewarding effects
      induced by morphine were significantly decreased in GAT1-overexpressing mice as
      measured by the conditioned place preference (CPP) paradigm. Moreover, both
      somatic and vegetative signs of naloxone-induced morphine withdrawal symptoms
      were substantially reduced in GAT1-overexpressing mice. In addition, the
      decreased morphine rewarding in transgenic mice could be recovered when mice were
      coinjected with NO-711 (a GAT1 selective inhibitor) in the CPP paradigm. These
      findings suggest that the GABAergic system plays an important role in morphine
      addiction and point to the possibility of developing drugs that target GAT1 and
      extend the clinical application of opiates.

PMID- 14598308
TI  - Centrally administered norepinephrine modifies the behavior induced by
      corticotropin-releasing factor in neonatal chicks.
AB  - We previously reported that glucagon-like peptide-1 decreased corticotropin
      releasing factor (CRF)-induced behaviors in neonatal chicks, and such an effect
      is hypothesized to act through norepinephrine (NE). Experiments were designed to
      explore the effect of the NE on CRF-induced behaviors. In experiment 1, the
      chicks were intracerebroventricularly (i.c.v.) administered saline, 0.1 microg of
      CRF, 50.0 microg of NE, or 0.1 microg of CRF with 50.0 microg of NE. Behavior was
      monitored for the 10 min immediately after i.c.v. injection, and plasma
      corticosterone was analyzed at the end of behavior tests. Compared with the
      control, chicks were excited by CRF as evidenced by increased spontaneous
      activity and distress vocalizations (DVs). NE decreased the spontaneous activity
      of chicks, and the differences diverged with time. DVs completely disappeared in
      the presence of NE, and sleep-like (sitting with eyes closed) behavior was
      observed in the same birds. NE-treated birds spent most of the time in a sleep
      like posture irrespective of CRF treatment. CRF-treated chicks had increased
      plasma corticosterone, whereas NE injection caused a decrease in corticosterone.
      In experiment 2, the effect of NE was further studied using i.c.v. administration
      with either 0.1 microg of CRF alone or 0.1 microg of CRF plus 12.5, 25.0, or 50.0
      microg of NE. NE dose dependently modified the CRF-induced locomotor activity in
      the open field, and DVs disappeared when chicks were given any dose of NE with
      CRF. With these findings taken together, it is suggested that central NE
      interacts the CRF-induced behaviors in neonatal chicks.

PMID- 14598310
TI  - ADAMs family members as amyloid precursor protein alpha-secretases.
AB  - In the non-amyloidogenic pathway, the Alzheimer's amyloid precursor protein (APP)
      is cleaved within the amyloid-beta domain by alpha-secretase precluding
      deposition of intact amyloid-beta peptide. The large ectodomain released from the
      cell surface by the action of alpha-secretase has several neuroprotective
      properties. Studies with protease inhibitors have shown that alpha-secretase is a
      zinc metalloproteinase, and several members of the adamalysin family of proteins,
      tumour necrosis factor-alpha convertase (TACE, ADAM17), ADAM10, and ADAM9, all
      fulfil some of the criteria required of alpha-secretase. We review the evidence
      for each of these ADAMs acting as the alpha-secretase. What seems to be emerging
      from numerous studies, including those with mice in which each of the ADAMs has
      been knocked out, is that there is a team of zinc metalloproteinases able to
      cleave APP at the alpha-secretase site. We also discuss how upregulation of alpha
      secretase activity by muscarinic agonists, cholesterol-lowering drugs, steroid
      hormones, non-steroidal anti-inflammatory drugs, and metal ions may explain some
      of the therapeutic actions of these agents in Alzheimer's disease.

PMID- 14598311
TI  - Identity and function of gamma-secretase.
AB  - gamma-Secretase catalyzes intramembrane proteolysis of various type I membrane
      proteins, including the amyloid-beta precursor protein and the Notch receptor.
      Despite its importance in the pathogenesis of Alzheimer's disease and to normal
      development, this protease has eluded identification until only very recently.
      Four membrane proteins are now known to be members of the protease complex:
      presenilin, nicastrin, aph-1, and pen-2. Recent findings suggest that these four
      proteins are sufficient to reconstitute the active gamma-secretase complex and
      that together they mediate the cell surface signaling of a variety of receptors
      via intramembrane proteolysis.

PMID- 14598312
TI  - Distinct presenilin-dependent and presenilin-independent gamma-secretases are
      responsible for total cellular Abeta production.
AB  - gamma-Secretase is the second of two proteolytic enzymes involved in the
      liberation of the beta-amyloid peptide (Abeta) from the amyloid precursor protein
      (APP). gamma-Secretase cleavage occurs at several intracellular sites, including
      the Golgi network and the endoplasmic reticulum/intermediate compartment (ER/IC)
      to produce multiple forms of the Abeta peptide that can be either secreted from
      the cell or remain intracellular. To date, most evidence has suggested that
      members of the presenilin protein family are required for gamma-secretase
      activity. Although it seems that presenilins are indeed necessary for the
      production of most secreted and intracellular Abeta particularly that generated
      in downstream organelles, it was shown recently that a presenilin-independent
      gamma-secretase is active in the ER/IC and is responsible for the production of a
      portion of intracellular Abeta42. We discuss the implications of this finding for
      the understanding of presenilin biology and speculate on the putative identity of
      the presenilin-independent cleavage activity.

PMID- 14598313
TI  - JLK isocoumarin inhibitors: selective gamma-secretase inhibitors that do not
      interfere with notch pathway in vitro or in vivo.
AB  - gamma-Secretase activity is involved in the generation of Abeta and therefore
      likely contributes to the pathology of Alzheimer's disease. Blocking this
      activity was seen as a major therapeutic target to slow down or arrest Abeta
      related AD progression. This strategy seemed more doubtful when it was
      established that gamma-secretase also targets other substrates including Notch, a
      particularly important transmembrane protein involved in vital functions, at both
      embryonic and adulthood stages. We have described previously new non-peptidic
      inhibitors able to selectively inhibit Abeta cellular production in vitro without
      altering Notch pathway. We show here that in vivo, these inhibitors do not alter
      the Notch pathway responsible for somitogenesis in the zebrafish embryo. In
      addition, we document further the selectivity of JLK inhibitors by showing that,
      unlike other described gamma-secretase inhibitors, these agents do not affect E
      cadherin processing. Finally, we establish that JLKs do not inhibit beta-site APP
      cleaving enzymes (BACE) 1 and BACE2, alpha-secretase, the proteasome, and
      GSK3beta kinase. Altogether, JLK inhibitors are the sole agents to date that are
      able to prevent Abeta production without triggering unwanted cleavages of other
      proteins.

PMID- 14598314
TI  - Proteasome-mediated degradation of the C-terminus of the Alzheimer's disease beta
      amyloid protein precursor: effect of C-terminal truncation on production of beta
      amyloid protein.
AB  - The beta-amyloid protein (Abeta) is derived by proteolytic processing of the
      amyloid protein precursor (APP). Cleavage of APP by beta-secretase generates a C
      terminal fragment (APP-CTFbeta), which is subsequently cleaved by gamma-secretase
      to produce Abeta. Our previous studies have shown that the proteasome can cleave
      the C-terminal cytoplasmic domain of APP. To identify proteasome cleavage sites
      in APP, two peptides homologous to the C-terminus of APP were incubated with
      recombinant 20S proteasome. Cleavage of the peptides was monitored by reversed
      phase high-performance liquid chromatography and mass spectrometry. Proteasome
      cleaved the APP C-terminal peptides at several sites, including a region around
      the sequence YENPTY that interacts with several APP-binding proteins. To examine
      the effect of this cleavage on Abeta production, APP-CTFbeta and mutant forms of
      APP-CTFbeta terminating on either side of the YENPTY sequence were expressed in
      CHO cells. Truncation of APP-CTFbeta on the N-terminal side of the YENPTY
      sequence at residue 677 significantly decreased the amount of Abeta produced,
      whereas truncation on the C-terminal side of residue 690 had little effect. The
      results suggest that proteasomal cleavage of the cytosolic domain of APP at the
      YENPTY sequence decreases gamma-secretase processing, and consequently inhibits
      Abeta production. Therefore, the proteasome-dependent trafficking pathway of APP
      may be a valid therapeutic target for altering Abeta production in the
      Alzheimer's disease brain.

PMID- 14598315
TI  - Proteolytic processing of the Alzheimer's disease amyloid precursor protein in
      brain and platelets.
AB  - Proteolytic processing of the amyloid precursor protein by beta -and gamma
      secretases results in the production of Alzheimer's disease (AD) Abeta amyloid
      peptides. Modulation of secretase activity is being investigated as a potential
      therapeutic approach. Recent studies with human brain have revealed that the beta
      secretase protein, BACE, is increased in cortex of AD patients. Analysis of
      betaCTF (or C99), the amyloid precursor protein (APP) product of BACE cleavage
      that is the direct precursor to Abeta, shows it is also elevated in AD,
      underlying the importance of beta-secretase cleavage in AD pathogenesis. The C
      terminal product of gamma-secretase cleavage of APP, epsilonCTF (or AICD), is
      enriched in human brain cortical nuclear fractions, a subcellular distribution
      appropriate for a putative involvement of APP cytosolic domain in signal
      transduction. Analysis of AD cortex samples, particularly that of a carrier of a
      familial APP mutation, suggests that processing of APP transmembrane domain
      generates an alternative CTF product. All these particularities observed in the
      AD brain demonstrate that APP processing is altered in AD. The transgenic mouse
      model Tg2576 seems to be a promising laboratory tool to test potential modulators
      of Abeta formation. Indeed, C-terminal products of alpha-, beta-, and gamma
      secretase cleavage are readily detectable in the brain of these transgenic mice.
      Finally, the finding of the same secretase products in platelets and neurons make
      platelets a potentially useful and easily accessible clinical tool to monitor
      effects of novel therapies based on inhibition of beta- or gamma-secretase.

PMID- 14598316
TI  - Cysteine proteases are the major beta-secretase in the regulated secretory
      pathway that provides most of the beta-amyloid in Alzheimer's disease: role of
      BACE 1 in the constitutive secretory pathway.
AB  - This article focuses on beta-amyloid (Abeta) peptide production and secretion in
      the regulated secretory pathway and how this process relates to accumulation of
      toxic Abeta in Alzheimer's disease. New findings are presented demonstrating that
      most of the Abeta is produced and secreted, in an activity-dependent manner,
      through the regulated secretory pathway in neurons. Only a minor portion of
      cellular Abeta is secreted via the basal, constitutive secretory pathway.
      Therefore, regulated secretory vesicles contain the primary beta-secretases that
      are responsible for producing the majority of secreted Abeta. Investigation of
      beta-secretase activity in regulated secretory vesicles of neuronal chromaffin
      cells demonstrated that cysteine proteases account for the majority of the beta
      secretase activity. BACE 1 is present in regulated secretory vesicles but
      provides only a small percentage of the beta-secretase activity. Moreover, the
      cysteine protease activities prefer to cleave the wild-type beta-secretase site,
      which is relevant to the majority of AD cases. In contrast, BACE 1 prefers to
      cleave the Swedish mutant beta-secretase site that is expressed in a minor
      percentage of the AD population. These new findings lead to a unifying hypothesis
      in which cysteine proteases are the major beta-secretases for the production of
      Abeta in the major regulated secretory pathway and BACE 1 is the beta-secretase
      responsible for Abeta production in the minor constitutive secretory pathway.
      These results indicate that inhibition of multiple proteases may be needed to
      decrease Abeta production as a therapeutic strategy for Alzheimer's disease.

PMID- 14598317
TI  - Role of proteolysis in polyglutamine disorders.
AB  - To date, nine polyglutamine disorders have been characterised, including
      Huntington's disease (HD), spinobulbar muscular atrophy (SBMA), dentatorubral
      pallidoluysian atrophy (DRPLA), and spinocerebellar ataxias 1, 2, 3, 6, 7 and 17
      (SCAs). Although knockout and transgenic mouse experiments suggest that a toxic
      gain of function is central to neuronal death in these diseases (with the
      probable exception of SCA6), the exact mechanisms of neurotoxicity remain
      contentious. A further conundrum is the characteristic distribution of neuronal
      damage in each disease, despite ubiquitous expression of the abnormal proteins.
      One mechanism that could possibly underlie the specific distribution of neuronal
      toxicity is proteolytic cleavage of the full-length expanded polyglutamine tract
      containing proteins. There is evidence found in vitro or in vivo (or both) of
      proteolytic cleavage in HD, SBMA, DRPLA, and SCAs 2, 3, and 7. In HD, cleavage
      has been demonstrated to be regionally specific, occurring as a result of caspase
      activation. These diseases are also characterised by development of intraneuronal
      aggregates of the abnormal protein that co-localise with components of the
      ubiquitin-proteasome pathway. It remains unclear whether these aggregates are
      pathogenic or merely disease markers; however, at least in the case of ataxin-3,
      cleavage promotes aggregation. Inhibition of specific proteases constitutes a
      potential therapeutic approach in these diseases.

PMID- 14598318
TI  - Extracellular matrix and matrix metalloproteinases in sciatic nerve.
AB  - Although matrix metalloproteinases (MMPs) are increasingly being implicated in
      several pathologies of the nervous system, it is not yet clear what role they
      play in normal neurobiological processes. We review the expression of
      extracellular matrix (ECM) components as well as MMPs and tissue inhibitors of
      metalloproteinases (TIMPs) in the peripheral nervous system. We explore the
      expression of certain MMPs and the four TIMPs at the mRNA level in the postnatal
      mouse sciatic nerve. In addition, we have used substrate gel and in situ
      zymography to determine levels of MMP-2 and -9 and TIMP activity in rat sciatic
      nerve after crush and during regeneration. A rapid and transient increase in MMP
      9 localised at and immediately distal to the site of injury was observed, whereas
      an increase in MMP-2 activity was delayed, prolonged, and extended proximal and
      distal to the injury site. This activity coincides with periods of axonal
      elongation, suggesting that it could act to facilitate axonal extension along the
      nerve matrix. We also detected multiple species of gelatinolytic inhibitory
      activity, including TIMP-1 and -3 in control and injured nerve. These activities
      probably act to prevent uncontrolled gelatinolytic activity, maintaining nerve
      integrity at the level essential for axonal regrowth.

PMID- 14598319
TI  - Mice lacking tissue plasminogen activator and urokinase plasminogen activator
      genes show attenuated matrix metalloproteases activity after sciatic nerve crush.
AB  - Plasminogen activators (PAs), tissue PA (tPA) and urokinase PA (uPA), have been
      shown to be induced in sensory neurons after sciatic nerve crush. These findings
      suggested that PAs facilitate peripheral nerve regeneration by digesting adhesive
      cell contacts and by activation of other proteases, thereby initiating a
      proteolytic cascade. Both tPA and uPA activate some matrix metalloproteases
      (MMPs), indirectly via plasminogen activation or directly, such as the uPA
      activation of MMP-2. In this study, we demonstrated, by using tPA and uPA
      knockout mice, that a lack of a plasminogen activator affected MMP-9 and MMP-2
      activity after crushing of the sciatic nerve. These findings show that the PAs
      are important for MMP-9 and MMP-2 activity at the crush site.

PMID- 14598321
TI  - Targeted mutagenesis of processing enzymes and regulators: implications for
      development and physiology.

PMID- 14598320
TI  - Caspase regulation of genotoxin-induced neural precursor cell death.
AB  - Neural precursor cells (NPCs) critically regulate brain morphogenesis and recent
      studies have revealed an unexpectedly high frequency of NPC chromosomal
      abnormalities and apoptosis in the developing brain. We have shown previously
      that the apoptotic response of NPCs to genotoxic agents is dependent on p53 and
      caspase-9, but not Bax or caspase-3 expression. In this study, we found that NPCs
      deficient in Apaf-1, or both the pro-apoptotic multidomain Bcl-2 family members
      Bax and Bak, were resistant to cytosine arabinoside and gamma-irradiation-induced
      apoptosis. Inhibitors of gene transcription, protein translation, and caspase
      activity also blocked genotoxin-induced NPC apoptosis. Although caspase-3 and
      caspase-6 were both cleaved in response to DNA damage, neither of these effector
      caspases was critical for apoptosis. Genotoxin-induced NPC death was accompanied
      by the generation of reactive oxygen species and could be inhibited by several
      known antioxidants. Conversely, DNA damage-induced reactive oxygen species
      generation was inhibited significantly by gene disruption of p53, Apaf-1, or
      caspase-9, and combined deficiency of Bax and Bak, but not by caspase-3 or
      caspase-6 deficiency. These studies suggest that caspase-9 activation is both
      necessary and sufficient for genotoxin-induced neural precursor cell reactive
      oxygen species generation and death.

PMID- 14598322
TI  - Novel roles of neuropeptide processing enzymes: EC3.4.24.15 in the neurome.
AB  - Neuropeptide processing metalloenzymes, such as angiotensin converting enzyme,
      neprilysin, endothelin converting enzyme, neurolysin, and EC3.4.24.15 (EP24.15),
      are central to the formation and degradation of bioactive peptides. We present
      EP24.15 as a paradigm for novel functions ascribed to these enzymes in the
      neurome. Although the neurome typically encompasses proteomes of the brain and
      central nervous system, exciting new roles of these neuropeptidases have been
      demonstrated in other organ systems. We discuss the involvement of EP24.15 with
      clinical sequelae involving the use of gonadotropin-releasing hormone (GnRH;
      LHRH) analogs that act as enzyme inhibitors, in vascular physiology (blood
      pressure regulation), and in the hematologic system (immune surveillance).
      Hemodynamic forces, such as cyclic strain and shear stress, on vascular cells,
      induce an increase in EP24.15 transcription, suggesting that neuropeptidase
      mediated hydrolysis of pressor/depressor peptides is likely regulated by changes
      in hemodynamic force and blood pressure. Lastly, EP24.15 regulates surface
      expression of major histocompatibility complex Class I proteins in vivo,
      suggesting that EP24.15 may play an important role in maintenance of immune
      privilege in sites of increased endogenous expression. In these extraneural
      systems, regulation of both neuropeptide and other peptide substrates by
      neuropeptidases indicates that the influence of these enzymes may be more global
      than was anticipated previously, and suggests that their attributed role as
      neuropeptidases underestimates their physiologic actions in the neural system.

PMID- 14598323
TI  - EP24.15 is associated with lipid rafts.
AB  - Metalloendopeptidase EC 3.4.24.15 (EP24.15, thimet oligopeptidase) is a
      neuropeptide-metabolizing peptidase expressed throughout the body, but primarily
      in the brain, gonads, and pituitary. For EP24.15 to have its greatest effect upon
      peptides in the periphery, it must be targeted and released into the
      extracellular space. Western blot analysis of fractions taken from discontinuous
      sucrose density gradients carried out on crude plasma membrane fractions from AtT
      20 cells reveals colocalization of EP24.15 and flotillin-1, a known lipid raft
      marker. Further analysis revealed that an intracellular membrane marker and non
      lipid raft, plasma membrane marker, failed to colocalize, supporting
      EP24.15/lipid raft association. Furthermore, EP24.15 immunoreactivity in lipid
      raft fractions generated from cells treated with methyl beta-cyclodextrin
      (MbetaCD) was greatly reduced. Finally, treatment with MbetaCD resulted in the
      accumulation of EP24.15 in the media of drug-treated cells over vehicle-treated
      cells, suggesting that a large percentage of EP24.15 associating with lipid rafts
      resides on the extracellular surface of the plasma membrane. With this exofacial
      localization, EP24.15 could have ample access to neuropeptides not only in the
      immediate microenvironment, but the ability to degrade or modify peptides bound
      for receptor interaction.

PMID- 14598324
TI  - Regulators of the neuropeptide-degrading enzyme, EC 3.4.24.15 (thimet
      oligopeptidase), in cerebrospinal fluid.
AB  - Endopeptidase EC 3.4.24.15 (EP 24.15; thimet oligopeptidase) is a soluble
      metalloendopeptidase implicated in the metabolism of a number of neuropeptides,
      including neurotensin, gonadotropin-releasing hormone, and opioid peptides. We
      have shown previously that thiol reducing agents, such as dithiothreitol,
      activate EP 24.15 by mediating the conversion of inactive multimeric forms to
      active monomers and that this conversion involves the disruption of
      intermolecular disulfide bonds involving cysteine residues 246, 248, and 253. We
      have identified two components of cerebrospinal fluid that activate recombinant
      EP 24.15, but have no effect on a thiol-independent cysteine mutant form of the
      enzyme. The low molecular weight (<10 kDa) component co-elutes with glutathione
      by reversed-phase HPLC, whereas the high molecular weight component (>50 kDa) is
      sensitive to digestion with trypsin, suggesting it is proteinaceous in nature.
      These results suggest that EP 24.15 activity in the brain may be modulated by
      factors released into cerebrospinal fluid.

PMID- 14598325
TI  - Resolution of enantiomers of ketoprofen by HPLC: a review.
AB  - Today, a heightened awareness of the applicability of enantiomers in medicine and
      clinical practice has been gene-rated due to the continuous evolvement of the
      field of chirality. In this context, this article provides a review of separation
      of ketoprofen, an important drug, in a popular class of non-steroidal anti
      inflammatory drugs (i.e. profens). This review highlights various methodologies,
      logistical considerations for separation and provides an exhaustive list of
      applications mainly focusing on the pharmacokinetic aspects. Clearly, the
      application of enantioselective methods for drug racemates paves the way to
      understand the in vivo behavior of individual enantiomer and hence an opportunity
      for an alternate and/or better option for treating the disease.

PMID- 14598326
TI  - Determination of the flavone tricin in human plasma by high-performance liquid
      chromatography.
AB  - Tricin is a flavone constituent of brown rice and rice bran, which interferes
      potently with the survival of human-derived breast and colon cancer cells in
      vitro. A specific and simple high-performance liquid chromatographic (HPLC)
      method was developed for the determination of tricin in human plasma with UV
      visible detection. HPLC separation on Hypersil-BDS C(18) (4.6 x 250 mm) was
      carried out with an isocratic mobile phase of 52% methanol in 0.1 m ammonium
      acetate, pH 5.10, containing 0.27 mm disodium ethylenediamine tetraacetic acid
      and detection at 355 nm. The retention times of tricin and quercetin (internal
      standard) were 14.2 and 7.8 min, respectively. The assay was linear in the range
      1-100 microg/mL (r(2 ) > or = 0.995). Tricin in plasma was efficiently extracted
      with 0.1 m acetic acid in acetone, and the recoveries were in the range 92.6
      102.8% (n = 6) with relative standard deviation below 10% for three
      concentrations of tricin, 5, 10 and 100 microg/mL. The lower limit of
      quantitation (relative standard deviation <20%) was 1 microg/mL.

PMID- 14598327
TI  - An HPLC-MS method for simultaneous estimation of alpha,beta-arteether and its
      metabolite dihydroartemisinin, in rat plasma for application to pharmacokinetic
      study.
AB  - This manuscript reports, the development and validation of a sensitive and
      selective assay method for simultaneous determination of alpha,beta-arteether and
      its metabolite dihydroartemisinin (DHA) in rat plasma by liquid chromatography
      mass spectrometry. Chromatographic separations were achieved by gradient elution
      of the analytes with an initial composition of methanol-potassium acetate buffer
      (pH 4; 73:27, v/v) to 100% methanol in 3 min and maintained for 5 min on a Spheri
      10, RP(18) (100 x 4.6 mm i.d.) column following an RP(18) (30 x 4.6 mm i.d.)
      guard column. The total effluent from the column was split so that one-tenth was
      injected into the electrospray LC/MS interface. ESI-MS analysis was performed
      using a Micromass Quattro II Triple Quadrupole Mass Spectrometer equipped with an
      electrospray source. The MS analysis was carried out at cone voltage of 22 V with
      a scan range of 200-500 Da. The analytes were quantified from the [M+ K](+) ion
      chromatograms of alpha,beta-arteether at m/z 352, DHA at m/z 323, artemisinin at
      m/z 321 and propyl ether analogue of arteether at m/z 365. Liquid-liquid
      extractions with a combination of n-hexane and hexane-ethyl acetate (8:2) were
      used to isolate alpha,beta-arteether and DHA from rat plasma. The method was
      validated and gave good accuracy and precision for the studied domain. Linearity
      in serum was observed over the range 4.375-70 ng/mL for alpha-arteether and 10
      160 ng/mL for beta-arteether and DHA. Percentage bias (accuracy) and within- and
      between-assay precision were well within the acceptable range. This method was
      applied to study the pharmacokinetics following oral administration of alpha,beta
      arteether (30 mg/kg) in rats.

PMID- 14598328
TI  - HPLC investigation of free and bound propofol in human plasma and cerebrospinal
      fluid.
AB  - The paper compares the total propofol concentration in the cerebrospinal fluid
      (CSF) with the free drug concentration in plasma measured in 35 humans scheduled
      for elective neurosurgical procedures during propofol anaesthesia. The
      concentrations of total and free propofol in the blood and CSF samples were
      measured by means of HPLC using liquid-liquid extraction and ultrafiltration in
      the sample preparation procedure. The arterial blood and CSF samples (collected
      from intraventricular drainage) were taken at the same time. According to the
      obtained results, the usually expected equality between free drug concentration
      in plasma and its total concentration in CSF is not valid for propofol: the
      unbound propofol concentration in plasma is not equal to its total concentration
      in CSF (p < 0.05). This difference suggests a substantial contribution of active
      transport in propofol transfer from blood into CSF. Moreover, the paper shows the
      presence of bound propofol in CSF, which is a novel finding.

PMID- 14598329
TI  - Enantioselective determination of arotinolol in human plasma by HPLC using
      teicoplanin chiral stationary phase.
AB  - A sensitive enantioselective high-performance liquid chromatography (HPLC) method
      was developed and validated to determine S-(+)- and R-(-)-arotinolol in human
      plasma. Baseline resolution was achieved by using teicoplanin macrocyclic
      antibiotic chiral stationary phase (CSP) known as Chirobiotic T with a polar
      organic mobile phase consisting of methanol:glacial acetic acid:triethylamine,
      100:0.1:0.1, (v/v/v) at a fl ow rate of 0.8 mL/min and UV detection set at 317
      nm. Human plasma was spiked with stock solution of arotinolol enantiomers and
      labetalol as the internal standard. The assay involved the use of liquid-liquid
      extraction procedure with ethyl ether under alkaline condition for human plasma
      sample prior to HPLC analysis. Recoveries for S-(+)- and R-(-)-arotinolol
      enantiomers were in the range 93-103% at 200-1400 ng/mL level. Intra-day and
      inter-day precision calculated as %RSD was in the ranges 1.3-3.4 and 1.9-4.5% for
      both enantiomers, respectively. Intra-day and inter-day accuracies calculated as
      percentage error were in the ranges 1.2-3.5 and 1.5-6.2% for both enantiomers,
      respectively. Linear calibration curves in the concentration range 100-1500 ng/mL
      for each enantiomer showed a correlation coefficient (r) of 0.9998. The limit of
      quantitation (LOQ) and limit of detection (LOD) for each enantiomer in human
      plasma were 100 and 50 ng/mL (S/N = 3), respectively.

PMID- 14598330
TI  - Simple high-performance liquid chromatographic assay for melphalan in perfusate,
      rat liver and tumour tissue.
AB  - A simple, sensitive and selective reversed-phase liquid chromatographic assay has
      been developed and validated for the anti-cancer agent melphalan in perfusate,
      liver and tumour tissue originating from isolated rat liver perfusion studies.
      Melphalan was extracted from the matrix using ice-cold methanol. The drug and the
      internal standard, propylparaben, were detected using ultraviolet absorbance at
      262 nm. The assay has been validated in the 0.05-25 microg/mL range for
      perfusate; the lower limit of quantification (LLQ) is 0.05 microg/mL in perfusate
      and 0.25 ng/mg in liver and tumour tissues. Accuracies ranged from 89 to 110% and
      the inter-assay precisions were all below 15% (20% at the LLQ). Melphalan in a
      biological matrix has to be processed between 0 and 4 degrees C and is stable
      under all relevant processing and storage conditions tested. The assay has been
      exhaustively used in isolated liver perfusion studies with the drug demonstrating
      its applicability.

PMID- 14598331
TI  - Direct injection HPLC method for the determination of selected phenothiazines in
      plasma using a Hisep column.
AB  - A direct plasma injection HPLC method has been developed for the determination of
      selected phenothiazines (promethazine, promazine, chlorpromazine) using a Hisep
      column. The method is easy to perform and requires 20 microL of a filtered plasma
      sample. The chromatographic run time is less than 11 min using a mobile phase of
      15:85 v/v acetonitrile-0.18 m ammonium acetate pH 5.0 and UV detection at 254 nm.
      The method is linear in the concentration range 0.1-25 microg mL(-1) (r > 0.99, n
      = 6) for each analyte with RSD less than 6%. Interday and intraday variability
      were found to be < or =14%. The limits of detection and quantitation were 0.1
      (S/N > 3) and 0.25 microg mL(-1) (S/N > 10), respectively, for each of the three
      phenothiazines. We can also apply this method to separate three other
      phenothiazines (ethopromazine, trifluoroperazine, prochlorperazine), although it
      lacks the selectivity to determine the concentration of all six drugs
      concurrently. The separation is feasible using these drugs in certain
      combinations.

PMID- 14598332
TI  - Determination of methamphetamine and amphetamine in abusers' plasma and hair
      samples with HPLC-FL.
AB  - This paper describes highly sensitive HPLC methods for the determination of
      amphetamine (AP) and methamphetamine (MP) in abusers' plasma and hair samples. AP
      and MP were derivatized with the fluorescent reagent, DIB-Cl, to yield a highly
      fluorescent DIB-derivatives of AP and MP, which were then analyzed by HPLC with
      fluorescence detection at excitation and emission wavelengths of 325 and 430 nm,
      respectively. The separation was achieved on an ODS column with isocratic mobile
      phases composed of acetoniltrile and citrate buffer (55:45, v/v) for plasma
      samples and of acetonitrile-methanol-citrate buffer (45:20:37.5, v/v/v) for hair
      samples. The limits of detection were less than 0.87 ng/mL and 0.12 ng/mg in
      plasma and hair samples, respectively, for both AP and MP. The methods were then
      applied to the determination of MP and its metabolite AP in plasma obtained from
      two cases of illegally ingested MP and in one of the cases' hair received later.
      Case I was treated with dialysis; samples before and after dialysis were analyzed
      by the described method. After dialysis for 5 h, the total plasma levels of AP
      and MP decreased from 720 to 190 ng/mL. For case II, MP and AP levels were
      monitored for 3 days after digestion. Total plasma levels decreased from 57 ng/mL
      in the day of digestion to 11 ng/mL after 3 days. In hair samples, AP and MP
      could also be detected in very low concentrations.

PMID- 14598333
TI  - Identification and determination of ecdysone and phenylpropanoid glucoside and
      flavonoids in Lamium maculatum by capillary zone electrophoresis.
AB  - The simultaneous determination of 20-hydroxy ecdysone (1), 3,7-dimethoxy
      quercetin (2), acteoside (3) and rutin (4) in the mixture of leaf and stem, and
      the flower of Lamium maculatum has been investigated by capillary zone
      electrophoresis for the first time. With an electrolyte containing 30 mmol/L
      borate, at pH 9.47 and 20 kV applied voltage, the four active compounds were
      completely separated within 5 min with satisfactory results. The effects of
      concentration of borate and electrolyte pH on electrophoretic behavior and
      separation were studied. Regression equations revealed linear relationships
      (correlation coefficients 0.9998-0.9999) between the peak area of each analyte
      and the concentration. The levels of analytes in the different parts of Lamium
      maculatum were easily determined with recoveries ranging from 98.3 to 105.0%.

PMID- 14598334
TI  - Determination of the compositions of polysaccharides from Chinese herbs by
      capillary zone electrophoresis with amperometric detection.
AB  - In this paper, capillary zone electrophoresis with amperometric detection (CZE
      AD) was applied to determine the compositions of hetero-polysaccharides from
      Chinese herbs, Angelica sinensis and flax by analyzing their hydrolyzed
      monosaccharides: fucose, galactose, glucose, arabinose, rhamnose and xylose.
      Under the selected optimum conditions, the six monosaccharides could be perfectly
      separated within 25 min and showed significant current responses at copper
      electrodes. The linear ranges of the six monosaccharides were all from 5.0 x 10(
      6) to 2.0 x 10(-4) mol L(-1) and their detection limits were lower or near 1.0 x
      10(-6) mol L(-1) (S/N = 3). Experiments showed that the Angelica sinensis
      polysaccharide was composed of fucose, galactose, glucose, arabinose, rhamnose
      and xylose (mole ratio 1.0:13.6:15.0:8.7:21.3:3.7), and the flax polysaccharide
      was composed of galactose, glucose and arabinose (mole ratio 1.0:4.98:1.1). The
      purity of these polysaccharides leached by the introduced leaching method was
      98.3 and 97.6%, respectively. Analyzing polysaccharides by this method has some
      merits of speed, simple instrumentation and operation, high sensitivity and high
      reproducibility.

PMID- 14598335
TI  - Preliminary data on changes in neural tube defect prevalence rates after folic
      acid fortification in South America.
AB  - Several South American countries are fortifying wheat flour with folic acid.
      However, only Chile started in 2000 to add 2.2 mg/kg, providing 360 microg daily
      per capita, an acceptable dosage for preventing the occurrence of some neural
      tube defect (NTD) cases. ECLAMC (Spanish acronym for the Latin American
      Collaborative Study of Congenital Malformations) routinely monitoring birth
      defects in South America since 1976, surveyed the impact of this fortification.
      Data from 361,374 births occurred in 43 South American hospitals, distributed in
      five different countries, active throughout the 1999-2001 triennium, were
      selected from the ECLAMC network. Birth prevalence rates for three different
      congenital anomalies with similar expected prevalence rates, were surveyed by the
      Cumulative Sum Method (CUSUM) method. They were NTD, oral clefts (OC), and Down
      syndrome (DS). Expected values were derived from observations made in 1999, and
      CUSUM was applied to the consecutive series of 24 months covering years 2000 and
      2001. Only one of three congenital anomaly types, NTDs, in only one of five
      sampled out countries, Chile, showed a significant decrease, of 31%, during the
      2000-2001 biennium, corresponding to the birth of the periconceptionally
      fortified infants. The level of significance (P < 0.001) was reached in the 20th
      month after fortification started, corresponding to August 2001. This is the
      first observation of a significant decrease in the occurrence of NTD after folic
      acid food fortification in a population little influenced by confounders common
      in the developed world as pre-existing secular decreasing trends, and partially
      unregistered induced abortions.

PMID- 14598336
TI  - MECP2 gene mutations in non-syndromic X-linked mental retardation: phenotype
      genotype correlation.
AB  - Non-syndromic X-linked mental retardation (MRX) is a frequent cause of inherited
      mental retardation. It is a heterogeneous condition in which the first 12 genes
      discovered to date explain no more than 15% of the MRX situations ascertained by
      recurrence in multiplex families. In Rett syndrome (RTT), an X-linked dominant
      condition mostly sporadic and usually lethal in males, most affected females have
      been shown to be mutated in the Methyl-CpG binding protein 2 gene (MECP2) that
      maps at Xq28. Some mentally retarded males related to RTT females carry the same
      mutation. Several MRX families mapping to Xq28 were subsequently tested for MECP2
      and a causative mutation was discovered in three families, suggesting that it
      could be one of the main genes involved in MRX. We report here the corresponding
      phenotypes in these three families of increasing severity. In family 1, an in
      frame deletion DeltaP387-M466 was found in the 3' region. The patients had severe
      to mild non-progressive MR, with better motor skills than verbal abilities. In
      family 2, an Arg to Trp substitution (R167W) was found between the transcription
      repression domain (TRD) and the methyl binding domain (MBD). The patients had
      brisk reflexes and essential tremor with mild and non-progressive MR, poor motor
      co-ordination and written language difficulties. In the third family (MRX16), a
      Glu to Gly substitution (E137G) was found in the MBD. The patients had
      manifestations similar to those of family 2, but MR was mild to moderate, speech
      articulation was poor and some had verbal stereotypies. Regression of language
      skills was suspected in three patients. Phenotype-genotype correlation could thus
      be suspected and is discussed in these three families.

PMID- 14598337
TI  - A genome-wide scan for loci predisposing to non-syndromic cleft lip with or
      without cleft palate in two large Syrian families.
AB  - Non-syndromic cleft lip with/without cleft palate (CL/P) is a common, usually non
      fatal birth defect of complex etiology. Several segregation analyses have
      demonstrated that genetic factors are important in the pathogenesis of CL/P, most
      likely through the interaction of several genes of modest effects. The aim of
      this study was to perform a genome-wide linkage analysis to identify/search for
      candidate gene loci for CL/P. We conducted a genome-wide search in two large,
      relatively isolated Syrian families, each one with a large number of cases with
      CL/P (18 in family 1 and 4 in family 2). A locus with a multipoint LOD score of
      2.80 and a 2-point non-parametric MLS LOD of 3.0 was detected on 17p13.1. Other
      chromosomal regions with multipoint LOD scores > or = 1.2 (P < or = 0.01)
      included 3p21.2, 4q32.1, and 7q34. These data indicate the possible presence of
      several susceptibility loci for CL/P and identify a strong candidate locus for
      this common birth defect on chromosome 17p13.

PMID- 14598338
TI  - Chromosome instability induced in vitro with mitomycin C in five Seckel syndrome
      patients.
AB  - Seckel syndrome (SS) is an autosomal recessive entity characterized by
      proportionate pre- and post-natal growth retardation, microcephaly, typical
      facial appearance with beak-like protrusion, and severe mental retardation. A
      heterogeneous basis for SS was proposed since around 25% of SS patients have
      hematological anomalies, suggesting a subgroup of SS with chromosome instability
      and hematological disorders. Chromosome instability induced by mitomycin C (MMC)
      has been observed in previous reports. The purpose of this study is to report
      cytogenetic features in five patients with SS. The patients had low birth weight
      (mean 1,870 g), short stature (SD = 6.36), microcephaly (OFC, SD = 8.1), typical
      facial appearance, and multiple articular dislocations. None of them had anemia
      at the time of examination. In all cases their parents were healthy and non
      consanguineous. Lymphocytes of SS patients and a control group (n = 9) matched by
      age and sex were cultured with and without MMC, and harvested at 72 and 96 hr.
      Chromosomal aberrations (chromatid and chromosomal gaps and breaks, deletions,
      fragments, and exchanges) were scored in 100 metaphases per culture. A
      statistical increase of chromosomal aberrations was observed in 96 hr MMC
      cultures in all patients (40.2% vs. 2.8%). Sister chromatid exchanges were also
      performed with no differences between groups. Clinical and cytogenetic findings
      support the idea that SS may correspond to a chromosome instability syndrome.

PMID- 14598339
TI  - Deletion of the distal long arm of chromosome 10; is there a characteristic
      phenotype? A report of 15 de novo and familial cases.
AB  - It has been suggested previously that patients with terminal deletions of
      chromosome 10q have a recognizable phenotype including a characteristic facial
      appearance combined with other abnormalities including mental retardation,
      cardiac and anogenital anomalies. We report the largest published series of new
      cases of terminal 10q deletion, including eight familial and four de novo cases
      and three cases with interstitial deletions involving chromosome bands 10q25.2
      26.3. The deleted regions were defined by FISH using YAC probes, as well as
      standard karyotyping. The most consistent clinical features in our cases are
      cranial anomalies including facial asymmetry, prominent nose and nasal bridge,
      prominent ears, thin upper lip, along with growth retardation, developmental
      delay, and digital abnormalities. Visceral abnormalities were only identified in
      a small number of the patients, with renal involvement in three cases and
      structural cardiac malformations in two others. Learning difficulties of varying
      severity were found in 11 cases and behavioral problems described in four.
      Candidate genes for behavioral and learning difficulties within the deleted
      region include Calcyon. Other genes in the region that might have a role in
      causing the phenotype include the genes coding for fibroblast growth factor
      receptor type 2 (FGFR2) and C-terminal binding protein 2 (CTBP2).

PMID- 14598340
TI  - Early renal insufficiency in a neonate with de novo partial trisomy of chromosome
      10q.
AB  - Partial trisomy of the long arm of chromosome 10 is a well-defined but rare
      syndrome. Clinical features of this chromosomopathy are a distinctive dysmorphic
      appearance, developmental delay, growth retardation, and in some cases,
      abnormalities of the extremities and renal, cardiac and ocular anomalies. This
      report describes a neonate with symmetric growth retardation and multiple
      dysmorphic features, in whom chromosomal analysis revealed a partial trisomy of
      chromosome 10q with a monosomy of the 13q34 region. The phenotype shares many
      common features with previously published cases. In addition to the typical
      features, our case also shows renal hypoplasia with early renal insufficiency and
      some genital anomalies.

PMID- 14598341
TI  - Novel mutation in the 5' splice site of exon 4 of the TCOF1 gene in the patient
      with Treacher Collins syndrome.
AB  - Treacher Collins syndrome (TCS) is caused by mutations in the TCOF1 gene. This
      gene encodes a serine/alanine-rich protein called treacle. The structure of the
      entire TCOF1 gene was investigated in a patient with TCS. We detected a novel
      deletion (376delAAGGTGAGTGGGACTGCC) spanning 3 bp of exon 4 and 15 bp of the
      adjacent intronic sequence. This mutation causes premature termination of
      translation, resulting in a truncated protein devoid of nucleolar localization
      signal, and potential phosphorylation sites. Real-time PCR analysis showed
      different melting temperatures of the amplified fragment containing normal allele
      and that harboring the 18 bp deletion, thus providing a rapid screening assay for
      this and other deletions of the TCOF1 gene.

PMID- 14598342
TI  - Novel homoplasmic mutation in the mitochondrial tRNATyr gene associated with
      atypical mitochondrial cytopathy presenting with focal segmental
      glomerulosclerosis.
AB  - We report a 9-year-old girl with a mitochondrial cytopathy preceded by steroid
      resistant focal segmental glomerulosclerosis (FSGS). The proband presented at the
      age of 2 years with steroid-resistant nephrotic syndrome caused by FSGS. Her
      renal function progressively deteriorated and a dilated cardiomyopathy developed
      at the age of 7 years. A skeletal muscle biopsy showed a combined respiratory
      chain (RC) defect and a partial deficiency of coenzyme Q(10). A novel mutation in
      the evolutionary highly conserved region of the mitochondrial tRNA(Tyr) gene was
      found in homoplasmic state in skeletal muscle, blood, and renal tissue. The
      mutation was also found in homoplasmic state in her mildly symptomatic mother. No
      other maternal family members were available for testing. The present case of
      mitochondrial cytopathy initially presenting with steroid-resistant nephrotic
      syndrome, unusual biochemical and renal findings associated with a novel tRNA
      point mutation suggests that steroid-resistant FSGS can predate other features of
      mitochondrial disease for a prolonged period of time and that the progressive
      glomerulopathy associated with combined mitochondrial RC defects is genetically
      heterogeneous.

PMID- 14598343
TI  - Oral-facial-digital syndrome VII is oral-facial-digital syndrome I: a
      clarification.
AB  - We report on further clinical findings in the one single family in the literature
      classified as oral-facial-digital (OFD) type VII in order to demonstrate that the
      diagnosis in this kindred should, in fact, be OFD type I. The mother and the
      daughter described in the original report have since developed polycystic kidney
      disease. In addition, the daughter recently had a daughter of her own with
      central nervous system, oral and digital anomalies. Linkage studies have shown
      that all the affected women share the same haplotype across the previously
      identified region Xp22.2p22.3 to which OFD I maps. Although the pedigree was too
      small for a significant lod score, the combination of clinical and molecular
      information clearly shows that the disease in this family is OFD I. We report
      this family in order to clarify and simplify the classification of the oral
      facial-digital syndrome spectrum and to recommend the removal of OFD VII from the
      classification system of the oral-facial-digital syndromes.

PMID- 14598344
TI  - Crisponi syndrome: report of a further patient.
AB  - Crisponi syndrome was described in the original paper in 17 patients form 12
      families [Crisponi, 1996: Am J Med Genet 62:365-371]. It is characterised by
      episodes of muscle contraction in response to external stimuli and intermittent
      hypethermia with neonatal onset. The disease is often lethal in the first
      infancy. We describe a patient with the same unusual phenotype.

PMID- 14598345
TI  - Werner mesomelic dysplasia with Hirschsprung disease.
AB  - Mesomelic dysplasia type Werner is defined by absence of tibiae and preaxial
      polysyndactyly of hands and feet. Occasional findings are triphalangeal thumbs,
      absence of patella(e), and dislocated fibula(e). The molecular basis is unknown
      and autosomal dominant inheritance with variable expressivity is currently
      postulated. Hirschsprung disease was reported previously in one case. We report
      here on a new case of mesomelic dysplasia Werner type associated with
      Hirschsprung disease and bilateral cryptorchidism. We discuss the overlap with
      the triphalangeal thumb polysyndactyly syndrome located in chromosome 7q36.

PMID- 14598347
TI  - Thrombocytopenia and absent radii, TAR syndrome: report of cerebellar dysgenesis
      and newly identified cardiac and renal anomalies.

PMID- 14598346
TI  - A revised allele frequency estimate and haplotype analysis of the DBH deficiency
      mutation IVS1+2T --> C in African- and European-Americans.

PMID- 14598348
TI  - Mutation screen of the gene encoding GABRB3 in Chinese patients with childhood
      absence epilepsy.

PMID- 14598349
TI  - Ring chromosome 10 (p15q26) in a patient with unipolar affective disorder,
      multiple minor anomalies, and mental retardation.

PMID- 14598350
TI  - Clinical homogeneity and genetic heterogeneity in Weill-Marchesani syndrome.
AB  - Weill-Marchesani syndrome (WMS) is a rare condition characterized by short
      stature, brachydactyly, joint stiffness, and characteristic eye abnormalities
      including microspherophakia, ectopia of lens, severe myopia, and glaucoma. Both
      autosomal recessive (AR) and autosomal dominant (AD) modes of inheritance have
      been described for WMS. A locus for AR WMS has recently been mapped to chromosome
      19p13.3-p13.2 while mutation within the fibrillin-1 gene (15q21.1) was found in
      one AD WMS family. In order to answer the question of whether or not genetic
      heterogeneity could be related to a clinical heterogeneity, we reviewed 128 WMS
      patients from the literature (including 57 AR, 50 AD, and 21 sporadic cases),
      with a particular attention to clinical features. Statistical analyses using
      Fischer exact test were used to compare the proportions of 12 clinical parameters
      between AR and AD patients. There was no significant difference between both
      groups for myopia, glaucoma, cataract, short stature, brachydactyly, thick skin,
      muscular build, and mental retardation. Significant results were found for
      microspherophakia (94% in AR, 74% in AD, Fischer 0.007), ectopia lentis (64% in
      AR, 84% in AD, Fischer 0.016), joint limitations (49% in AR, 77% in AD, Fischer
      0.010), and cardiac anomalies (39% in AR, 13% in AD, Fischer 0.004).
      Nevertheless, we failed to distinguish AR from AD inheritance in individual
      cases. These results support the clinical homogeneity but the genetic
      heterogeneity of WMS.

PMID- 14598352
TI  - Surgical quality assurance in breast, gastric and rectal cancer.

PMID- 14598353
TI  - The potential of non-steroidal anti-inflammatory drugs (NSAIDs) for colorectal
      cancer prevention.

PMID- 14598354
TI  - Impact of lymph node retrieval and pathological ultra-staging on the prognosis of
      stage II colon cancer.
AB  - BACKGROUND AND OBJECTIVES: A minimum number of lymph nodes must be assessed for
      accurate diagnosis of stage II colon cancer. We assessed number of lymph nodes
      retrieved, pathological ultra-staging, and outcome in stage II colon cancer.
      MATERIALS AND METHODS: Consecutively treated patients with stage II colon cancer
      were identified. Baseline and outcome data were collected. Retrospective ultra
      staging using lymphovascular invasion (LVI) and nodal micrometastases was
      performed. Patients were divided into two groups: group I had <or=6 nodes and
      group II had >6 nodes retrieved. Survival was analyzed. RESULTS: One hundred and
      fifteen patients were included in the study. The 5 year overall survival was
      worse in group I versus II (P = 0.03). LVI and micrometastases were identified
      but neither predicted survival. Disease failure in group I was due to distant
      metastases rather than local recurrence. CONCLUSIONS: Inadequate retrieval and
      assessment of lymph nodes is associated with worse outcome in stage II colon
      cancer patients. Recurrence patterns support the hypothesis that disease
      recurrence occurred due to inaccurate staging. In this small study, LVI or nodal
      micrometastases did not predict survival. Maximal attention should be paid to the
      total number of lymph nodes retrieved before embarking on potentially more
      resource intensive staging methods.

PMID- 14598355
TI  - Prospective evaluation of prognostic factors in patients with colorectal cancer
      undergoing curative resection.
AB  - BACKGROUND AND OBJECTIVES: Streak type, defined by the presence of white streaks
      at the advancing margin of tumor invasion; focal dedifferentiation, seen as
      undifferentiated cancer cells with an infiltrative pattern at the invasive front;
      and perineural invasion have been demonstrated to be prognostic factors in
      patients with colorectal cancer. We performed a prospective study to examine the
      usefulness of these features as prognostic factors. METHODS: We reviewed a total
      of 391 patients who underwent curative surgery for colorectal cancer between May
      1997 and June 1999. Of these, 50 patients with multiple cancers were excluded,
      and a total of 341 patients were finally entered into the study. RESULTS: Of the
      prognostic factors investigated, depth of invasion, lymph node status, lymphatic
      invasion, venous invasion, growth type, streak type, focal dedifferentiation, and
      perineural invasion were significant prognostic factors in univariate analysis.
      In multivariate analysis, lymph node status, depth of invasion, and perineural
      invasion were significant prognostic factors. The survival of patients with
      perineural invasion was significantly poorer than that of patients without
      perineural invasion in both stage II and III cancer. CONCLUSIONS: Perineural
      invasion status can be used to facilitate the selection of colorectal cancer
      patients for adjuvant chemotherapy and should be described in routine pathology
      reports.

PMID- 14598356
TI  - Mortality for gastric cancer in elderly patients.
AB  - BACKGROUND: The aim of this study was to clarify the surgical outcome in elderly
      patients with gastric cancer. METHODS: The clinicopathological features of
      elderly patients (80 (3.7%), over 80 years, elderly group) were reviewed
      retrospectively and compared with those of younger patients (2095 (96.3%), 23-79
      years, control group). RESULTS: The elderly group had a significantly higher
      prevalence of concomitant disease (P < 0.0001), while the prevalence of T1
      primary tumor, N0 lymph node metastasis, and stage I was lower (P = 0.0125, P =
      0.0004, P < 0.0001). The rates of resected cases and curative operation (R0) were
      significantly lower in the elderly group (P < 0.0001, P = 0.0021). The mortality
      from other diseases was 16.3% in elderly patients and 4.4% in control patients (P
      < 0.0001). The 5-year survival of stage I and stage IV were not significantly
      different between the two groups (P = 0.1266 and P = 0.2490). The overall
      survival and disease-specific survival for all patients in the elderly group were
      significantly lower than those in the control group (P < 0.0001, P = 0.0102).
      However, disease-specific survival for resected cases was not significantly
      different between the two groups (P = 0.0725). CONCLUSIONS: In elderly patients,
      the reason for the poor prognosis is the high rate of advanced stage and the high
      rate of death from other diseases.

PMID- 14598357
TI  - Effects of major liver resection, with or without recombinant
      bactericidal/permeability-increasing protein (rBPI21), on the angiogenic profile
      of patients with metastatic colorectal carcinoma.
AB  - BACKGROUND: Surgery induces a process of wound healing, which has immunological
      and angiogenic aspects. Bactericidal/permeability-increasing protein (BPI) is
      found in azurophilic granules of human neutrophils, which is bactericidal and
      neutralizes lipo-polysaccharide (LPS). This may reduce postoperative infectious
      complications. In addition, BPI has been shown to be an inhibitor of
      angiogenesis. METHODS: A total of 18 patients with metastasized colorectal
      carcinoma to the liver were double blind randomized. The levels of the pro
      angiogenic factors interleukin-6 (IL-6) and vascular endothelial growth factor
      (VEGF) and the angiogenesis inhibitor endostatin were investigated after liver
      surgery with perioperative administration of either rBPI(21) or placebo. RESULTS:
      The highest IL-6 levels were found during the first 24 hr and reached peak levels
      already at 2 hr postoperatively in both groups. In both groups VEGF levels
      decreased sharply in the postoperative hours, returning to baseline levels in the
      days afterwards. In both groups, an immediate decrease in endostatin levels was
      observed which remained significantly low. RBPI(21) transiently influenced IL-6
      and VEGF. CONCLUSIONS: RBPI(21) only marginally affected IL-6 and VEGF levels.
      Surgery per se induced an immediate immune response (IL-6) and an immediate
      angiogenic response, reflected in an initial VEGF decrease and a longer lasting
      decrease of endostatin. These findings demonstrate the dynamics of tissue
      responses in the first phase of wound healing.

PMID- 14598358
TI  - Inactivation of p16INK4a by CpG hypermethylation is not a frequent event in
      colorectal cancer.
AB  - BACKGROUND AND OBJECTIVES: Gene promoter hypermethylation is common in colorectal
      cancer and is associated with transcriptional silencing. However, the
      clinicopathological significance of p16(INK4a) gene silencing with
      hypermethylation is unknown. Therefore, the aim of this study was to analyze loss
      of p16 expression and its relationship to hypermethylation in sporadic colorectal
      cancer. METHODS: Tissue from 426 colorectal cancers underwent histological
      analysis. Immunohistochemistry was performed for p16 expression. Fresh tumor DNA
      was analyzed for microsatellite instability (MSI) and the presence of K-ras
      mutations. In addition, DNA was bisulphite-modified and analyzed for p16(INK4a)
      promoter methylation by methylation-specific PCR. RESULTS: There were 25% of
      tumors with p16(INK4a) promoter hypermethylation. These tumors were associated
      with older patients, right-sidedness, MSI and were poorly differentiated,
      mucinous, and had intraepithelial and peritumoral lymphocytes and a Crohn's-type
      lymphocytic reaction (P < 0.05). However, only right-sidedness was significant on
      multivariate analysis (P < 0.001). Only 8.1% of tumors did not express p16, and
      this was associated with hypermethylation (P < 0.05). CONCLUSION: p16(INK4a)
      promoter methylation, although common in colorectal cancer, does not result in a
      clinicopathologically distinct subgroup of tumors and infrequently results in
      transcriptional silencing. This suggests that p16(INK4a) gene inactivation does
      not have an important role in the pathogenesis of sporadic colorectal cancer.

PMID- 14598359
TI  - Cytokine and cytokine receptor serum levels in adult bone sarcoma patients:
      correlations with local tumor extent and prognosis.
AB  - BACKGROUND AND OBJECTIVES: We analyzed the correlations between pretreatment
      serum levels of 11 cytokines and soluble cytokine receptors (interleukin 6 (IL
      6); interleukin 8 (IL-8); interleukin 10 (IL-10); vascular endothelial growth
      factor (VEGF); basic fibroblast growth factor (bFGF); macrophage colony
      stimulating factor (M-CSF); granulocyte colony-stimulating factor (G-CSF);
      interleukin 1 receptor antagonist (IL-1ra); sIL-2Ralpha; tumor necrosis factor
      receptor I (TNF RI), and TNF RII) with clinico-pathological features and survival
      of patients with bone sarcomas. METHODS: Altogether, 72 patients with bone
      sarcomas without distant metastases before treatment (26 osteosarcomas-36%, 23
      chondrosarcomas-32%, 13 Ewing's sarcomas/PNET-18%, 10 giant-cell tumors-14%), 22
      patients with benign non-inflammatory bone tumors and 50 age-matched healthy
      controls were included into this prospective study. RESULTS: Median serum levels
      of 9/11 cytokines, with the exception of sIL-2Ralpha and G-CSF, were
      significantly higher in sarcoma patients than in controls. Median serum levels of
      IL-6, IL-8, IL-1ra, TNF RI, and M-CSF were significantly higher in patients with
      bone sarcoma as compared to patients with benign bone tumors. In 45.9% of sarcoma
      patients, six or more cytokines and cytokine receptors, including those that are
      involved in bone destruction (e.g., IL-6 and IL-8) and bone formation (e.g., IL
      1ra and TNFRI and TNFRII), were elevated in parallel. Serum levels of IL-6, IL-8,
      TNF RI, TNF RII, and VEGF correlated significantly with tumor size (<10 cm vs.
      >or=10 cm in diameter) and serum levels of IL-6, IL-8, TNF RI, and IL-1ra
      correlated significantly with local tumor extent (E2/4 vs. E5/6 according to the
      classification proposed by Spanier et al. 46). Moreover, serum levels of IL-1ra
      and IL-6 were significantly higher in patients with small tumors (<5 cm in
      diameter) infiltrating structures adjacent to the periosteum (E5/6) than in large
      tumors (>10 cm in diameter) but confined to the bone and periosteum (E < 4). The
      lowest median serum levels of 8/11 cytokines/cytokine receptors were found in
      patients with giant-cell tumors. In an univariate analysis, increased serum
      levels of IL-1ra, IL-6, IL-8, IL-10, sIL-2Ralpha, M-CSF, TNF RI, and TNF RII, the
      number of cytokines elevated, higher tumor grade, larger tumor size, greater
      local extent (E) and patients' age >35 years correlated with poor overall
      survival (OS) (P < 0.05). Similarly, high serum levels of IL-1ra, IL-6, TNF RI
      and TNF RII, tumor grade, tumor size, and tumor local extent (E) (P < 0.05)
      affected disease free survival (DFS) in univariate analysis. Multivariate
      analysis using Cox's proportional hazards model showed that high serum levels of
      IL-1ra (P = 0.039) and TNF RI (P = 0.048), the number of serum cytokines above
      normal cut-off values (0-1 vs. 2-5 vs. >or=6; P = 0.029), greater tumor local
      extent E (E2/4 vs. E5/6; P = 0.02) correlated significantly with shorter OS. Only
      E was found as an independent prognostic factor for DFS (P = 0.04). CONCLUSIONS:
      These findings indicate that cytokines and soluble cytokine receptors, both
      physiologically involved in bone destruction and bone formation, have an
      essential role in the progression of malignant bone tumors.

PMID- 14598361
TI  - Expression of PTEN in renal cell carcinoma and its relation to tumor behavior and
      growth.
AB  - BACKGROUND AND OBJECTIVES: PTEN is a candidate tumor suppressor gene in a variety
      of malignant tumors, including renal cell carcinoma (RCC). PTEN regulates cell
      cycle progression and cell survival in vivo. However, the role of PTEN
      alterations and their association with tumor growth and behavior in patients with
      RCC has not been well established. The aim of our study was to evaluate PTEN
      expression in RCC and its correlation with clinicopathologic features, cell
      proliferation, and apoptosis. METHODS: Sixty-seven RCC specimens were examined
      immunohistochemically with anti-PTEN antibody. The apoptotic cells were
      visualized by terminal deoxynucleotidyl transferase (TdT) mediated dUTP nick-end
      labeling (TUNEL) and proliferative cells were visualized by staining with Ki-67
      antibody. RESULTS: Twenty-one (31.3%) of the 67 RCCs showed reduced PTEN
      expression. The apoptotic index (AI) varied from 0.2 to 25.5%, and the Ki-67
      index (KI) ranged from 1.6 to 69.8%. Reduced PTEN expression correlated with TNM
      stage (P < 0.05) and nuclear grade (P < 0.05). Tumors with reduced PTEN
      expression had a significantly higher KI than those with normal PTEN expression
      (P < 0.01). By univariate analysis, nuclear grade (P = 0.0005), TNM stage (P <
      0.0001), AI (P = 0.0220), KI (P = 0.0002), and reduced PTEN expression (P <
      0.0001) were associated with shortened survival. However, TNM stage was the only
      independent prognostic factors by multivariate analysis (P = 0.0007).
      CONCLUSIONS: Our results suggest that PTEN expression is frequently reduced in
      advanced RCC. The PTEN gene seems to be important for the growth suppression of
      RCC, by inhibiting cell proliferation.

PMID- 14598360
TI  - Application of 99mTc labeled chimeric Fab fragments of monoclonal antibody A7 for
      immunoscintigraphy of pancreatic carcinoma.
AB  - BACKGROUND: One of the reasons for the poor prognosis of pancreatic carcinoma is
      the difficulty of obtaining an early diagnosis of pancreatic carcinoma. One
      possibility is the application of radioimmunoscintigraphy using radiolabeled
      monoclonal antibodies (Mabs). METHODS: We labeled chimeric (human/mouse) Fab
      fragments of Mab A7 (chA7Fab) with (99m)Tc and examined the distribution of
      (99m)Tc-labeled chA7Fab in nude mice bearing human pancreatic carcinoma. RESULTS:
      The tumor accumulation of (99m)Tc-labeled chA7Fab was larger than that of (99m)Tc
      labeled A7 from 2 to 6 hr after injection. (99m)Tc-labeled chA7Fab disappeared
      from blood more rapidly than (99m)Tc-labeled A7. For all resected normal tissues
      except kidney, the accumulation of (99m)Tc-labeled chA7Fab was low and similar to
      that of (99m)Tc-labeled A7. CONCLUSIONS: Because the half-life of (99m)Tc is
      short (6 hr), chA7Fab, which accumulates rapidly in tumors, may be a better
      carrier of (99m)Tc than intact Mab A7.

PMID- 14598362
TI  - Emerging patterns of practice in the implementation and application of sentinel
      lymph node biopsy in breast cancer patients in Japan.

PMID- 14598363
TI  - Precision handling of the sentinel node.

PMID- 14598364
TI  - Flank incision for adenocarcinoma of the splenic flexure in the obese.

PMID- 14598365
TI  - Functions of the cytoskeleton in neural development. Introduction.

PMID- 14598366
TI  - Slow axonal transport and the genesis of neuronal morphology.
AB  - The classic view of slow axonal transport maintains that microtubules,
      neurofilaments, and actin filaments move down the axon relatively coherently at
      rates significantly slower than those characteristic of known motor proteins.
      Recent studies indicate that the movement of these cytoskeletal polymers is
      actually rapid, asynchronous, intermittent, and most probably fueled by familiar
      motors such as kinesins, myosins, and cytoplasmic dynein. This new view, which is
      supported by both live-cell imaging and mechanistic analyses, suggests that slow
      axonal transport is both rapid and plastic, and hence could underlie
      transformations in neuronal morphology.

PMID- 14598367
TI  - Actin and microtubules in neurite initiation: are MAPs the missing link?
AB  - During neurite initiation microtubules align to form a tight bundle and actin
      filaments reorganize to produce a growth cone. The mechanisms that underlie these
      highly coordinated cytoskeletal rearrangements are not yet fully understood.
      Recently, various levels of coordination between the actin- and microtubule-based
      cytoskeletons have been observed during cellular migration and morphogenesis,
      processes that share some similarities to neurite initiation. Direct, physical
      association between both cytoskeletons has been suggested, because microtubules
      often preferentially grow along actin bundles and transiently target actin-rich
      adhesion complexes. We propose that such physical association might be involved
      in force-based interactions and spatial organization of the two networks during
      neurite initiation as well. In addition, many signaling cascades that affect
      actin filaments are also involved in the regulation of microtubule dynamics, and
      vice versa. Although several candidates for mediating these effects have been
      identified in non-neuronal cells, the general mechanism is still poorly
      understood. In neurons certain plakins and neuron-specific microtubule associated
      proteins (MAPs), like MAP1B and MAP2, which can bind to both microtubules and F
      actin, are promising candidates to play key roles in the specific cytoskeletal
      rearrangements controlling the transition from an undifferentiated state to
      neurite-bearing morphology. Here we review the effects of MAPs on microtubules
      and actin, as well as the coordination of both cytoskeletons during neurite
      initiation.

PMID- 14598368
TI  - Role of CRMP-2 in neuronal polarity.
AB  - Of the several types of polarized cells, the neuron is one of the most dramatic
      examples. It extends two distinctive processes, axon and dendrite. Polarization
      in neurons enables the two processes to play their functionally different roles,
      sending and receiving electrical signals in a vectorial fashion. While a catalog
      of structural, molecular, and functional differences between axon and dendrite is
      accumulating, the mechanisms involved in establishment of neuronal polarity are
      not well understood. Neuronal polarity formation begins with the elongation of
      one process as an axon in a symmetric cell phase. In this review, we describe
      recent advances in the understanding of several cellular events in the early
      development of axon and dendrite. We also discuss the involvement of the Rho
      family small GTPases, their upstream and downstream molecules, and collapsin
      response mediator protein-2 (CRMP-2) in the regulation of neuronal polarity.

PMID- 14598369
TI  - Microtubule-associated protein 1B function during normal development,
      regeneration, and pathological conditions in the nervous system.
AB  - Microtubule-associated protein 1B is the first MAP to be expressed during the
      development of the nervous system. Several different approaches have revealed
      that MAP1B function is associated with microtubule and actin microfilament
      polymerization and dynamics. In recent years, the generation of molecular models
      to inactivate MAP1B function in invertebrates and mammals has sparked some
      controversy about the real role of MAP1B. Despite discrepancies between some
      studies, it is clear that MAP1B plays a principal role in the development of the
      nervous system. In this article, we summarize the evidence for MAP1B function in
      a wide variety of cellular processes implicated in the proper construction of the
      nervous system. We also discuss the role of MAP1B in pathological processes.

PMID- 14598370
TI  - Role of the microtubule destabilizing proteins SCG10 and stathmin in neuronal
      growth.
AB  - The related proteins SCG10 and stathmin are highly expressed in the developing
      nervous system. Recently it was discovered that they are potent microtubule
      destabilizing factors. While stathmin is expressed in a variety of cell types and
      shows a cytosolic distribution, SCG10 is neuron-specific and membrane-associated.
      It contains an N-terminal targeting sequence that mediates its transport to the
      growing tips of axons and dendrites. SCG10 accumulates in the central domain of
      the growth cone, a region that also contains highly dynamic microtubules. These
      dynamic microtubules are known to be important for growth cone advance and
      responses to guidance cues. Because overexpression of SCG10 strongly enhances
      neurite outgrowth, SCG10 appears to be an important factor for the dynamic
      assembly and disassembly of growth cone microtubules during axonal elongation.
      Phosphorylation negatively regulates the microtubule destabilizing activity of
      SCG10 and stathmin, suggesting that these proteins may link extracellular signals
      to the rearrangement of the neuronal cytoskeleton. A role for these proteins in
      axonal elongation is also supported by their growth-associated expression pattern
      in nervous system development as well as during neuronal regeneration.

PMID- 14598371
TI  - Microtubules and growth cone function.
AB  - It has been recognized for a long time that the neuronal cytoskeleton plays an
      important part in neurite growth and growth cone pathfinding, the mechanism by
      which growing axons find an appropriate route through the developing embryo to
      their target cells. In the growth cone, many intracellular signaling pathways
      that are activated by guidance cues converge on the growth cone cytoskeleton and
      regulate its dynamics. Most of the research effort in this area has focussed on
      the actin, microfilament cytoskeleton of the growth cone, principally because it
      underlies growth cone motility, the extension and retraction of filopodia and
      lamellipodia, and these structures are the first to encounter guidance cues
      during growth cone advance. However, more recently, it has become apparent that
      the microtubule cytoskeleton also has a role in growth cone pathfinding and is
      also regulated by guidance cues operating through intracellular signaling
      pathways via engagement with cell membrane receptors. Furthermore, recent work
      has revealed an interaction between these two components of the growth cone
      cytoskeleton that is probably essential for growth cone turning, a fundamental
      growth cone behavior during pathfinding. In this short review I discuss recent
      experiments that uncover the function of microtubules in growth cones, how their
      behavior is regulated, and how they interact with the actin filaments.

PMID- 14598372
TI  - How actin filaments and microtubules steer growth cones to their targets.
AB  - Guidance molecules steer growth cones to their targets by attracting or repelling
      them. Turning in a new direction requires remodeling of the growth cone and
      bending of the axon. This depends upon reorganization of actin filaments and
      microtubules, which are the primary cytoskeletal components of growth cones. This
      article discusses how these cytoskeletal components induce turning. The
      importance of each component as well as how interactions between them result in
      axon guidance is discussed. Current evidence shows that microtubules are
      influenced by both the organization and dynamics of actin filaments in the
      peripheral domain of growth cones. Cytoskeletal models for repulsive and
      attractive turning are presented. Molecular candidates that may link actin
      filaments with microtubules are suggested and potential signal transduction
      pathways that allow these cytoskeletal components to affect each other are
      discussed.

PMID- 14598373
TI  - Regulation of growth cone actin filaments by guidance cues.
AB  - The motile behaviors of growth cones at the ends of elongating axons determine
      pathways of axonal connections in developing nervous systems. Growth cones
      express receptors for molecular guidance cues in the local environment, and
      receptor-guidance cue binding initiates cytoplasmic signaling that regulates the
      cytoskeleton to control growth cone advance, turning, and branching behaviors.
      The dynamic actin filaments of growth cones are frequently targets of this
      regulatory signaling. Rho GTPases are key mediators of signaling by guidance
      cues, although much remains to be learned about how growth cone responses are
      orchestrated by Rho GTPase signaling to change the dynamics of polymerization,
      transport, and disassembly of actin filaments. Binding of neurotrophins to Trk
      and p75 receptors on growth cones triggers changes in actin filament dynamics to
      regulate several aspects of growth cone behaviors. Activation of Trk receptors
      mediates local accumulation of actin filaments, while neurotrophin binding to p75
      triggers local decrease in RhoA signaling that promotes lengthening of filopodia.
      Semaphorin IIIA and ephrin-A2 are guidance cues that trigger avoidance or
      repulsion of certain growth cones, and in vitro responses to these proteins
      include growth cone collapse. Dynamic changes in the activities of Rho GTPases
      appear to mediate responses to these cues, although it remains unclear what the
      changes are in actin filament distribution and dynamic reorganization that result
      in growth cone collapse. Growth cones in vivo simultaneously encounter positive
      and negative guidance cues, and thus, growth cone behaviors during axonal
      pathfinding reflect the complex integration of multiple signaling activities.

PMID- 14598374
TI  - Regulation of the neuronal actin cytoskeleton by ADF/cofilin.
AB  - Actin and microtubules are major cytoskeletal elements of most cells including
      neurons. In order for a cell to move and change shape, its cytoskeleton must
      undergo rearrangements that involve breaking down and reforming filaments. Many
      recent reviews have focused on the signaling pathways emanating from receptors
      that ultimately affect axon growth and growth cone steering. This particular
      review will address changes in the actin cytoskeleton modulated by the family of
      actin dynamizing proteins known as actin depolymerizing factor (ADF)/cofilin or
      AC proteins. Though much is known about inactivation of AC proteins through
      phosphorylation at ser3 by LIM or TES kinases, new mechanisms of regulation of AC
      have recently emerged. A novel phosphatase, slingshot (SSH), and the 14-3-3
      family of regulatory proteins have also been found to affect AC activity. The
      potential role of AC proteins in modulating the actin organizational changes that
      accompany neurite initiation, axonogenesis, growth cone guidance, and dendritic
      spine formation will be discussed.

PMID- 14598375
TI  - Myosin function in nervous and sensory systems.
AB  - Development of the nervous system requires remarkable changes in cell structure
      that are dependent upon the cytoskeleton. The importance of specific components
      of the neuronal cytoskeleton, such as microtubules and neurofilaments, to
      neuronal function and development has been well established. Recently, increasing
      focus has been put on understanding the functional role of the actin cytoskeleton
      in neurons. Important modulators of the actin cytoskeleton are the large family
      of myosins, many of which (classes I, II, III, V, VI, VII, IX, and XV; Fig. 1)
      are expressed in developing neurons or sensory cells. Myosins are force-producing
      proteins that have been implicated in a wide variety of cellular functions in the
      developing nervous system, including neuronal migration, process outgrowth, and
      growth cone motility, as well as other aspects of morphogenesis, axonal
      transport, and synaptic and sensory functions. We review the roles that neuronal
      myosins play in these functions with particular focus on the first three events
      listed above, as well as sensory function.

PMID- 14598376
TI  - Functions of intermediate filaments in neuronal development and disease.
AB  - Five major types of intermediate filament (IF) proteins are expressed in mature
      neurons: the three neurofilament proteins (NF-L, NF-M, and NF-H), alpha
      internexin, and peripherin. While the differential expression of IF genes during
      embryonic development suggests potential functions of these proteins in
      axogenesis, none of the IF gene knockout experiments in mice caused gross
      developmental defects of the nervous system. Yet, deficiencies in neuronal IF
      proteins are not completely innocuous. Substantial developmental loss of motor
      axons was detected in mice lacking NF-L and in double knockout NF-M;NF-H mice,
      supporting the view of a role for IFs in axon stabilization. Moreover, the
      absence of peripherin resulted in approximately 30% loss of small sensory axons.
      Mice lacking NF-L had a scarcity of IF structures and exhibited a severe axonal
      hypotrophy, causing up to 50% reduction in conduction velocity, a feature that
      would be very detrimental for large animal species. Unexpectedly, the NF-M rather
      than NF-H protein turned out to be required for proper radial growth of large
      myelinated axons. Studies with transgenic mice suggest that some types of IF
      accumulations, reminiscent of those found in amyotrophic lateral sclerosis (ALS),
      can have deleterious effects and even cause neurodegeneration. Additional
      evidence for the involvement of IFs in pathogenesis came from the recent
      discovery of neurofilament gene mutations linked to ALS and Charcot-Marie-Tooth
      disease (CMT2E). Conversely, we discuss how certain types of perikaryal
      neurofilament aggregates might confer protection in motor neuron disease.

PMID- 14598377
TI  - Cytoskeletal-associated proteins in the migration of cortical neurons.
AB  - Neuronal migration is a hallmark of cerebral cortical development as neurons born
      deep within the brain migrate to the surface in a highly choreographed process.
      The cytoskeleton extends throughout the cell, mediating the dramatic
      morphological changes that accompany migration. On a cellular level, proper
      migration is accompanied by polarization of the cytoskeleton and cellular
      contents and by dynamic reorganization that generates the force for cell
      locomotion. Genetic analyses of human brain malformations, as well as genetically
      engineered mouse mutants, have highlighted a number of cytoskeletal-associated
      proteins underlying these functions, which are necessary for proper cortical
      development. While these proteins are involved in diverse molecular mechanisms,
      disruption during development results in the ectopic placement of neurons in the
      cortex. We review key cytoskeletal events and the critical cytoskeletal
      associated proteins involved in cortical neuronal migration.

PMID- 14598379
TI  - Foreword to symposium "forty years of epithelial transport-specificity and
      commonality": a tribute to Professor Jose A Zadunaisky.

PMID- 14598380
TI  - The fall and rise of active chloride transport: implications for regulation of
      intraocular pressure.
AB  - Early study of transepithelial salt transfer focused on Cl(-) and not Na(+),
      partly because Cl(-) was readily measureable. The advent of flame photometry and
      tracer techniques brought Na(+) to the fore, especially since short-circuited
      frog skin (Rana temporaria) produces baseline net movement of Na(+) and not of
      Cl(-). Zadunaisky was among the first to describe what is currently termed
      secondary active Cl(-) transport, helping stimulate interest in Cl(-) handling by
      other tissues, notably the thick ascending limb of the loop of Henle important in
      renal counter-current multiplication. More recently, molecules responsible for
      electroneutral and electrogenic Cl(-) transfer have been cloned, and specific
      diseases resulting from their faulty expression have been identified. The
      clinical importance of transepithelial Cl(-) transfer is illustrated by studies
      of aqueous humor formation by the eye's bilayered ciliary epithelium. NaCl is
      taken up from the stroma by the pigmented ciliary epithelial (PE) layer, diffuses
      through gap junctions into the nonpigmented ciliary epithelial (NPE) layer, and
      is released into the aqueous humor largely through Na(+) pumps and Cl(-)
      channels. ATP released by NPE cells can be ecto-enzymatically metabolized to
      adenosine. Adenosine can mediate paracrine/autocrine stimulation of Cl(-)
      channels and aqueous humor secretion by occupying A(3) adenosine receptors (ARs).
      A(3)AR agonists indeed elevate, and A(3)AR antagonists lower, intraocular
      pressure (IOP) in wild-type mice. A(3)AR knockout mice have low IOP and their
      responses to A(3)AR agonists and antagonists are blunted; this suggests that
      reducing Cl(-)-channel activity with A(3)AR antagonists may provide a novel
      approach for treating glaucoma.

PMID- 14598381
TI  - Purinergic signaling in the rabbit ciliary body epithelium.
AB  - In the past forty years, a wealth of information has accumulated that points to
      the presence of adenosine and adenine nucleotides in the anterior segment of the
      eye and a number of hypotheses have been introduced to describe the possible role
      of these agents in the regulation of aqueous humor flow. However, in the absence
      of a generally accepted model for the cellular and molecular mechanisms of
      aqueous humor formation by the ciliary body epithelium, efforts to identify the
      signal transduction pathway(s) responsible for regulation of the ion and water
      transport have not been successful. This article briefly reviews the evidence for
      (i). the presence in aqueous humor of adenine nucleotides, cyclic adenosine
      monophosphate and adenosine, their metabolic product, (ii). the possible role of
      these agents in the regulation of aqueous humor dynamics, and (iii). the
      expression of ecto-nucleotidases, receptors, and second messengers that may
      mediate such regulation. Finally, a model for the regulation of aqueous humor
      formation by adenosine and ATP is proposed.

PMID- 14598382
TI  - Regulation of Na,K-ATPase function in the lens.
AB  - The two cell types in the lens, epithelium and fiber, have a very different
      specific activity of Na,K-ATPase; activity is much higher in the epithelium.
      However, judged by Western blot, fibers and epithelium express a similar amount
      of both Na,K-ATPase alpha and beta subunit proteins. Na,K-ATPase protein
      abundance does not tally with Na,K-ATPase activity. Studies were conducted to
      examine whether protein synthesis plays a role in maintenance of the high Na,K
      ATPase activity in lens epithelium. An increase of cytoplasmic sodium was found
      to increase Na,K-ATPase protein expression in the epithelium, but not in the
      fibers. The findings illustrate the ability of lens epithelium to synthesize new
      Na,K-ATPase protein as a way to boost Na,K-ATPase in response to cell damage or
      pathological events. Methionine incorporation studies suggested Na,K-ATPase
      synthesis may also play a role in day to day preservation of high Na,K-ATPase
      activity. Na,K-ATPase protein in lens epithelial cells appeared to be continually
      synthesized and degraded. Experiments with cycloheximide suggest that specific
      activity of Na,K-ATPase in the lens epithelium may depend on the ability of the
      cells to continuously synthesize fresh Na,K-ATPase proteins. However, other
      factors such as phosphorylation of Na,K-ATPase alpha subunit may also influence
      Na,K-ATPase activity. When intact lenses were exposed to the agonist thrombin,
      Na,K-ATPase activity was diminished, but the response was suppressed by
      inhibitors of the Src family of non-receptor tyrosine kinases. Thrombin elicited
      tyrosine phosphorylation of lens epithelium membrane proteins, including a 100
      kDa protein band thought to be the Na,K-ATPase alpha 1 subunit. It remains to be
      determined whether a tyrosine phosphorylation mechanism contributes to the low
      activity of Na,K-ATPase in lens fibers.

PMID- 14598383
TI  - On the mechanism of fluid transport across corneal endothelium and epithelia in
      general.
AB  - The mechanism by which fluid is transported across epithelial layers is still
      unclear. The prevalent idea is that fluid traverses these layers transcellularly,
      driven by local osmotic gradients secondary to electrolyte transport and
      utilizing the high osmotic permeability of aquaporins. However, recent findings
      that some aquaporin knockout mice epithelia transport fluid sow doubts on local
      osmosis. This review discusses recent evidence in corneal endothelium that points
      instead to electro-osmosis as the mechanism underlying fluid transport. In this
      concept, a local recirculating electrical current would result in electro-osmotic
      coupling at the level of the intercellular junctions, dragging fluid via the
      paracellular route. The text also mentions possible mechanisms for apical
      bicarbonate exit from endothelial cells, and discusses whether electro-osmosis
      could be a general mechanism.

PMID- 14598384
TI  - The ocular lens fiber membrane specific protein MIP/Aquaporin 0.

PMID- 14598385
TI  - Mechanisms and functional aspects of intestinal calcium absorption.
AB  - Calcium absorption, in terms of mechanisms and function, is well adapted to meet
      the calcium needs of mammals. When calcium levels in the food are low, the
      active, mediated transcellular calcium transport assumes primary importance. This
      process is vitamin D-dependent, largely localized in the duodenum, and involves
      three steps: entry across the brush border, mediated by a molecular structure,
      CaT1, with two components; a facilitated transport that saturates at low luminal
      calcium concentration; and a channel component through which most calcium enters
      the cell at the higher luminal concentrations. Intracellular diffusion is assured
      by a small, cytosolic calcium binding molecule, calbindinD(9k), which carries
      more than 90% of the calcium that traverses the duodenal cell, thus also serving
      as a buffer. Extrusion is by the CaATPase and is not a limiting step. Calcium
      entry is reduced by more than 90% in the absence of vitamin D, with biosynthesis
      of calbindinD(9k) totally vitamin D-dependent. Active transport is upregulated on
      low calcium intake and downregulated at high calcium intake, when paracellular
      calcium transport through the tight junctions of the intestine becomes the
      dominant process. The amount of calcium absorbed paracellularly is a function of
      the calcium gradient between lumen and plasma and of the time the chyme spends at
      a given intestinal site. The coexistence of mediated and nonmediated transport
      processes assures the organism of an adequate calcium supply, yet prevents
      excessive calcium absorption.

PMID- 14598386
TI  - Channels, pumps, and exchangers in the gill and kidney of freshwater fishes:
      their role in ionic and acid-base regulation.
AB  - In freshwater fishes, the gill and kidney are intricately involved in ionic and
      acid-base regulation owing to the presence of numerous ion channels, pumps, or
      exchangers. This review summarizes recent developments in branchial and renal ion
      transport physiology and presents several models that integrate epithelial ion
      and acid-base movements in freshwater fishes. At the gill, three cell types are
      potentially involved in ionic uptake: pavement cells, mitochondria-rich (MR)
      PNA(+) cells, and MR PNA(-) cells. The transfer of acidic or basic equivalents
      between the fish and its environment is accomplished largely by the gill and is
      appropriately regulated to correct acid-base imbalances. The kidney, while less
      important than the gill in overall acid or base excretion, has an essential role
      in regulating systemic acid-base balance by controlling HCO(3) (-) reabsorption
      from the filtrate.

PMID- 14598387
TI  - Cl- absorption in European eel intestine and its regulation.
AB  - The intestinal epithelium of the euryhaline teleost fish, Anguilla anguilla,
      absorbs Cl(-) transepithelially. This gives rise to a negative transepithelial
      potential at the basolateral side of the epithelium and to a measured short
      circuit current. Cl(-) absorption occurs via bumetanide-sensitive Na(+)-K(+)-2Cl(
      ) cotransport, localized on the luminal membrane. The cotransport operates in
      parallel with a luminal K(+) conductance that recycles the ion into the lumen.
      Cl(-) leaves the cell across the basolateral membrane by way of Cl(-) conductance
      and presumably via a KCl cotransport. The driving force for this process is
      provided by the electrochemical sodium gradient across the plasma membrane,
      generated and maintained by the basolateral Na(+)-K(+)-ATPase. The resulting NaCl
      absorption process is active and enables marine fish to take up water, thereby
      compensating for water that was lost passively from the body. Fresh water
      acclimatized eel also absorb Cl(-) actively, although in smaller quantities,
      utilizing the same ion transport mechanisms as marine eels. This mechanism is
      basically the same as the model proposed for the thick ascending limb (cTAL). Cl(
      ) absorption is regulated by a number of cellular factors, such as HCO(3) (-),
      pH, Ca(2+), cyclic nucleotides, and cytoskeletal elements. It is sensitive to
      osmotic stress, and therefore is a good physiological model to study ion
      transport mechanisms that are activated when osmotic stress induces cell volume
      regulation. The activation of these various ion transport pathways is dependent
      on cellular transduction mechanisms in which phosphorylation events (mainly by
      PKC and MLCK for the hypertonic response) and cytoskeletal elements, either
      microfilaments or microtubules, seem to play key roles.

PMID- 14598388
TI  - CFTR: what's it like inside the pore?
AB  - The Cystic Fibrosis Conductance Regulator (CFTR) functions as a cAMP-activated,
      anion-selective channel, but the structural basis for anion permeation is not
      well understood. Here we summarize recent studies aimed at understanding how
      anions move through the CFTR channel, and the nature of the environment anions
      experience inside the pore. From these studies it is apparent that anion
      permeability selectivity and anion binding selectivity of the pore are consistent
      with a model based on a "dielectric tunnel." The selectivity pattern for halides
      and pseudohalides can be predicted if it is assumed that permeant anions
      partition between bulk water and a polarizable space that is characterized by an
      effective dielectric constant of about 19. Covalent labeling of engineered
      cysteines and pH titration of engineered cysteines and histidines lead to the
      conclusion that the CFTR anion conduction path includes a positively charged
      outer vestibule. A residue in transmembrane segment 6 (TM6) (R334) appears to
      reside in the outer vestibule of the CFTR pore where it creates a positive
      electrostatic potential that enhances anion conduction.

PMID- 14598389
TI  - Voltage-Gated ion currents of schwann cells in cell culture models of human
      neurofibromatosis.
AB  - K(+) (K) channels play a role in the proliferation of many cell types in normal
      cells and certain disease states. Several laboratories have studied K currents in
      cultured Schwann cells from models of the human diseases, neurofibromatosis type
      1 (NF1) and neurofibromatosis type 2 (NF2). These diseases are characterized by
      the growth of Schwann cell tumors. In all cell culture NF models the K current
      properties differ in tumor-derived and normal Schwann cells. Depending on the
      model however, the type of K channel abnormality differs. K channels appear to
      play a role in the proliferation of Schwann cell cultures of these disease
      models, because a link has been established between K current blockade and the
      inhibition of Schwann cell proliferation in NF1 and NF2. Differences in the
      proliferation response of normal Schwann cells to K channel blockers suggest that
      in vitro regulation of proliferation in neoplastic and normal Schwann cells is
      complex.

PMID- 14598390
TI  - Confocal imaging of xenobiotic transport across the blood-brain barrier.
AB  - The brain capillary endothelium is a formidable barrier to entry of foreign
      chemicals into the central nervous system (CNS). For the most part it poorly
      distinguishes between therapeutics and neurotoxins and thus the blood-brain
      barrier both protects the brain from toxic chemicals and limits our ability to
      treat a variety of CNS disorders. Two elements underlie the barrier function of
      the brain capillary endothelium: 1). a physical barrier comprised of tight
      junctions, which form an effective seal to intercellular diffusion, and the cells
      themselves, which exhibit a low rate of endocytosis, and 2). a metabolic/active
      barrier, comprised of specific membrane transporters expressed by the endothelial
      cells. We have recently developed an experimental system based on confocal
      microscopy to study mechanisms of transport in freshly isolated brain
      capillaries. Here I review studies demonstrating a major role for the ATP-driven,
      xenobiotic export pump, p-glycoprotein, in barrier function and recent
      experiments showing that transient inhibition of pump function can have
      substantial benefit for chemotherapy in an animal model of brain cancer.

PMID- 14598391
TI  - The xenobiotic transporter, MRP2, in epithelia from insects, sharks, and the
      human breast: implications for health and disease.
AB  - A large number of mechanisms, including special excretory transporters, have
      evolved to help organisms excrete deleterious xenobiotics and endogenous
      molecules. We have examined the xenobiotic transport function of a putative
      multidrug resistance associated protein, MRP2, in three different epithelia: the
      insect renal (Malpighian) tubules, the secretory tubule of the shark rectal
      gland, and in ductules of the human breast. In the case of the insect and shark,
      transporter activity occurs in epithelia capable of great fluid transport. In the
      case of the insect Malpighian tubule, understanding the underlying mechanisms of
      this transporter may help with efforts to control populations of disease-carrying
      agriculturally important insects. In striking contrast, ductule architecture in
      nonlactating human breast ductules is that of an epithelium with a closed lumen.
      Immunocytochemical studies show that MRP2 is localized in the apical region of
      the ductule epithelial cells. In this unique case, MRP2 substrates transported
      into the lumen could possibly be concentrated. Transport substrates of MRP2
      include carcinogens as well as antioxidants and other salutary molecules. Thus,
      in the breast ductule, MRP2 may play a significant role in breast epithelial cell
      health and cancer carcinogenesis.

PMID- 14598394
TI  - Osteoconductive and hemostatic properties of apatite formed on/in agarose gel as
      a bone-grafting material.
AB  - The biologic behavior of hydroxyapatite formed on/in agarose (HA/agarose) gels
      with the use of a novel alternate soaking process was compared with commercially
      available Bone Ject (True-Bone ceramic-collagen combined bone-graft material,
      Koken, Japan) as a filler for the tooth-extraction sockets of six adult monkeys
      (Macasa fascicularis). After the monkeys' first premolars were extracted, the
      defects created were replaced with one of the following materials: (a).
      HA/agarose created by 12 soaking cycles, (b). HA/agarose created by 9 soaking
      cycles, (c). Bone Ject, and (d). no material implantation (control). The time of
      hemostasis in each extraction site was estimated, and the samples were then
      studied histologically. In the controls, the time of hemostasis was about 5 min.
      The Bone Ject particles were easily washed out by bleeding, and the time of
      hemostasis was about 15 min. The HA/agarose gel was densely packed into the bony
      defect. The hemorrhage from the defects stopped within a few seconds after graft
      placement. This hemostasis was most likely related to the compactibility and
      adhesiveness of the material. After 12 weeks of implantation, free Bone Ject
      particles surrounded by inflammatory cells were observed. The bony defect filled
      with the HA/agarose gels was completely absorbed and replaced by newly formed
      bone possessing bone marrow. There was no difference in the biologic behavior of
      HA/agarose gels created by 9 versus 12 soaking cycles. The present study suggests
      that HA/agarose gels may play an important role as an alternative biodegradable
      bone-graft material for autogenous bone in humans.

PMID- 14598393
TI  - Electrospun nanofibrous polyurethane membrane as wound dressing.
AB  - Produced via electrospinning, polyurethane membrane, which has a unique property,
      has been of interest in medical fields. Electrospinning is a process by which
      nanofibers can be produced by an electrostatically driven jet of polymer
      solution. Electrospun fibers are collected in the form of membranes. The porous
      structured electrospun membrane is particularly important for its favorable
      properties: it exudates fluid from the wound, does not build up under the
      covering, and does not cause wound desiccation. The electrospun nanofibrous
      membrane shows controlled evaporative water loss, excellent oxygen permeability,
      and promoted fluid drainage ability, but still it can inhibit exogenous
      microorganism invasion because its pores are ultra-fine. Histological examination
      indicates that the rate of epithelialization is increased and the dermis becomes
      well organized if wounds are covered with electrospun nanofibrous membrane. This
      electrospun membrane has potential applications for wound dressing based upon its
      unique properties.

PMID- 14598395
TI  - Premixed calcium-phosphate cement pastes.
AB  - A self-hardening calcium-phosphate cement (CPC) containing Ca(4)(PO(4))(2)O and
      CaHPO(4) has been shown in clinical studies to be efficacious for repairing bone
      defects. This and several other similar CPCs harden in 10 min with the use of a
      phosphate solution as the liquid and form hydroxyapatite (HA) as the product. The
      present study investigated the properties of water-free, glycerol-containing CPC
      pastes that are stable in the package and would harden only after being delivered
      to a defect site where glycerol-tissue fluids exchange occurs. Premixed CPC
      pastes were prepared by combining cement liquids containing glycerol and various
      amounts of hydroxypropyl methylcellulose/Na(2)HPO(4), with CPC powders that
      contained (1) Ca(4)(PO(4))(2)O and CaHPO(4), (2) alpha-Ca(3)(PO(4))(2) and
      CaCO(3), or (3) CaHPO(4) and Ca(OH)(2). The hardening times and 1-d and 7-d
      diametral tensile strengths were measured on samples that hardened in an in vitro
      model that allowed exchange of glycerol and physiologic-like solution (PLS)
      through fritted glass slides at 37 degrees C. All pastes had excellent washout
      resistance; they remained intact and hardened while immersed in PLS and formed HA
      as products. Newman-Keuls multiple comparison tests indicated that the
      Na(2)HPO(4) amount, not the hydroxypropyl methylcellulose (HMC) amount,
      significantly (p < 0.05) affected the strength and hardening time. Although the
      premixed CPCs generally have longer hardening times and lower strengths, these
      pastes have excellent washout resistance before hardening and can be prepared in
      advance under well-controlled conditions.

PMID- 14598396
TI  - Control of material stiffness during degradation for constructs made of
      absorbable polymer fibers.
AB  - Augmentation devices for cruciate ligament surgery should provide gradually
      decreasing mechanical properties with a half-time strength of at least 6 months
      to temporarily protect healing tendon grafts or sutured ligaments against high
      tensile loads during the postoperative healing period. The absorbable material of
      choice that shows such slow degradation kinetics is poly(L-lactide). However,
      previous studies have shown that poly(L-lactide) fulfills the requirement of a
      long half-time strength, while the corresponding stiffness decreases at a much
      slower rate. An augmentation stiffness that does not change much versus time
      cannot provide a gradual increase in graft load, which is important to stimulate
      the orientation of the collagenous tissue. Therefore a new augmentation device
      was designed, which should decrease both in strength and stiffness during
      degradation. The cord was braided out of two fibers made of poly(L-lactide) and
      poly(L-lactide-co-glycolide), which degrade at different rates. The cord
      prototype was degraded in vitro and the rupture force and stiffness was tested at
      eight different time points up to 60 weeks. The initial rupture force and
      stiffness was 522.7 +/- 2.8 N and 104.1 +/- 3.8 N/%, respectively. Both strength
      and stiffness decreased continuously with a half-time strength of 18 weeks and a
      half-time stiffness of 39 weeks. The gradually decreasing stiffness was achieved
      by the breakdown of the faster-degrading fiber component made of poly(L-lactide
      co-glycolide). Thus the new augmentation device can provide a continuous increase
      of forces in a tendon graft or in a healing ligament.

PMID- 14598397
TI  - Facial nerve regeneration through progesterone-loaded chitosan prosthesis. A
      preliminary report.
AB  - Biodegradable nerve guides have represented new treatment alternatives for nerve
      repairing. They are gradually biodegradable, exert biological effects directly to
      the injured nerve, and act as drug- or cell-delivery devices. Furthermore,
      progesterone (PROG) has been demonstrated to promote injured peripheral nerve
      regeneration. In this study, it was hypothesized that PROG delivered from
      chitosan prostheses provides better facial nerve regenerative response than
      chitosan prostheses with no PROG. As there are no reports on the use of the
      former as nerve-guide material in the regeneration of injured nerves, this is the
      main objective of the present work. Chitosan prostheses containing PROG were used
      to bridge 10-mm gaps in rabbit facial nerves. The regenerated nerves were
      evaluated 45 days after implantation in animals with the use of light microscopy
      and morphometric analysis. Gas chromatography was used in order to quantify PROG
      content in prosthesis prior to and after implantation in subcutaneous tissue at
      different periods of up to 60 days. In addition, the prosthesis walls were
      evaluated with histological techniques in order to assess their integrity and the
      surrounding tissue reaction. Chitosan prostheses allowed PROG release during the
      time needed for nerve regeneration. At 45 days myelinated nerve fibers were
      observed in both the proximal and distal stumps. This parameter and the N ratio
      were higher in the progesterone-treated group when compared to that of the
      vehicle control. Findings indicate that chitosan prostheses were useful in nerve
      regeneration, acting as a long-lasting PROG delivery device a faster nerve
      regeneration.

PMID- 14598398
TI  - Evaluation of the fatigue behavior of the resin-dentin bond with the use of
      different methods.
AB  - The clinical performance of directly bonded resin composites is fundamentally
      dependent on durable adhesion to prevent gap formation over time. The goal of
      this investigation was to evaluate the effectiveness of various dentin adhesives
      by means of quasistatic and dynamic dentin bond strengths, and also to determine
      marginal and internal gap formation after loading in an artificial oral
      environment. Three hundred thirty human third molars were used within four weeks
      of extraction. Adhesives used were A.R.T. Bond, OptiBond FL, Scotchbond Multi
      Purpose Plus, Single Bond, Prime & Bond NT, and One Up Bond F for bonding of one
      resin composite (Z 250). Buccal and lingual aspects of 90 teeth were ground flat
      to expose dentin, then resin composite cylinders were bonded. Initial bond
      strengths (n = 10) and adhesive fatigue limits (n = 20) were determined with the
      use of a shear test apparatus. One hundred eighty conical cavities were prepared
      into dentin discs and filled with the same materials. After 21 days of storage,
      initial push-out bond strengths (n = 10) and adhesive fatigue limits (n = 20)
      were measured. Sixty molars with MO cavities (n = 10) with margins below the
      cement-enamel junction were filled. Before and after thermomechanical loading
      (100000 x 50 N and 2500 x thermocycling between + 5 and + 55 degrees C), marginal
      gap formation and internal adaptation (only after loading) were analyzed under a
      SEM (x 200). The one-bottle systems showed higher shear bond strengths when
      evaluated statically and dynamically. However, cyclic fatigue push-out bond
      strengths resulted in higher values for older multistep systems. Marginal and
      internal gap analysis confirmed the results, in favor of older adhesive systems
      (p <.05; Mann-Whitney U test).

PMID- 14598399
TI  - In vitro cytotoxicity testing of AB-polymer networks based on oligo(epsilon
      caprolactone) segments after different sterilization techniques.
AB  - Recently developed versatile biodegradable polymeric biomaterial offer new
      therapeutic options in numerous medical fields. Biocompatibility is a crucial
      requirement for the biomedical application of biomaterials, including the
      sterilization of these materials with the use of accepted protocols. Ethylene
      oxide (EO) and low-temperature plasma (LTP) sterilization are frequently used low
      temperature sterilization technologies for heat-sensitive materials. The agarose
      diffusion assay is a recommended cell-screening test to assess the cytotoxicity
      of biomaterials in vitro. The sensitivity of the agarose assay can be increased
      by using a modified computer-based image-analysis system. The influence of EO and
      LTP sterilization on the cytotoxicity of a versatile polymer system of shape
      memory polymer networks based on oligo (epsilon-caprolactone) dimethacrylate and
      n-butyl acrylate was investigated. Statistically significant differences in the
      rate of cell lysis after EO and LTP sterilization of the polymer samples were
      detected by using this modified quantification system. The influence of the
      different sterilization techniques on the cytotoxicity of the polymeric material,
      as well as the clinical relevance of the described differences, are discussed.

PMID- 14598400
TI  - Preparation of interconnected highly porous polymeric structures by a replication
      and freeze-drying process.
AB  - Three-dimensional degradable porous polymeric structures with high porosities (93
      98%) and well-interconnected pore networks have been prepared by freeze-drying
      polymer solutions in the presence of a leachable template followed by leaching of
      the template. Templates of the pore network were prepared by fusing sugar or salt
      particles to form a well-connected structure. The interstices of the template
      were then filled with a polymer solution (5-15% w/v) in 1,4-dioxane, followed by
      freeze-drying of the solvent. Subsequent leaching of the sugar template ensures
      the connectivity of the pore network. The scaffold architecture consists of
      relatively large interconnected pores modeled after the template and smaller
      pores resulting from the freeze-drying process. The total porosity of the
      resultant porous structures is determined by the interstitial space of the
      leachable template and by the polymer concentration in the freeze-drying
      solution. The freezing temperature also has an effect on the final morphology of
      the porous structures. Compared with freeze-drying and combination of freeze
      drying /particulate leaching techniques, this method facilitates higher
      interconnectivity of the scaffolds. Porous structures have been prepared from
      several relevant polymers in the biomedical and tissue-engineering field:
      poly(D,L-lactide) (PDLLA), 1000PEOT70PBT30, a segmented poly(ether ester) based
      on polyethylene oxide and polybutylene terephthalate, and poly(epsilon
      caprolactone) (PCL). The mechanical properties of the porous structures prepared
      by this technique depend on the nature of the polymer, porosity, and the freezing
      temperature. With porosities in the range of 95-97%, the compression moduli of
      scaffolds prepared from the different polymers could be varied between 13.0 and
      301.5 kPa.

PMID- 14598401
TI  - Generation of narrowly distributed ultra-high-molecular-weight polyethylene
      particles by surface texturing techniques.
AB  - Ultra-high-molecular-weight polyethylene (UHMWPE) wear particles have been
      recognized as the cause of aseptic loosening in total joint replacement.
      Macrophage phagocytosis of wear particles induces human biological/physiological
      responses which eventually lead to bone resorption and osteolysis. However, the
      dependence of these reactions on the size and shape of the particles has not been
      elucidated and is not understood. This article describes a procedure to generate
      narrowly distributed UHMWPE particles of controlled size and shape through
      surface texturing by microfabrication. The textured surface is then used to rub
      against the polymer pins to produce wear particles in water. The surface texture
      produces elongated particles or equiaxed particles by design. The distribution of
      the particles, due to the surface-texture control, is quite narrow as compared
      with randomly produced surfaces. With this technique, we are able to generate
      UHMWPE wear particles of different size and shape within phagocytosable and
      nonphagocytosable populations for biological response studies.

PMID- 14598402
TI  - Ion release and chromosomal damage from total hip prostheses with metal-on-metal
      articulation.
AB  - A prospective multicentric study was carried out in patients having metal-on
      metal METASUL components (Sulzer Medica, Winterthur, Switzerland) in order to
      check the following null hypotheses: H1: The concentration of Co, Cr, Ni, and Mb
      in blood and urine is not modified by the implant of a hip prosthesis with
      METASUL components at 6 months. H2: The incidence of markers of chromosomal
      damage [sister chromatid exchanges (SCEs) and micronuclei (Mni)] in lymphocytes
      is not modified by the implant of METASUL components at 6 months. H3: The
      concentrations of Co, Cr, Ni, and Mb in blood and urine did not correlate with
      the incidence of the markers of chromosomal damage. The measurements showed a 2
      fold increase of Co in blood, a 10-fold increase of Co in urine, a 1.5-fold
      increase of Cr in the blood, and a 3-fold increase of Cr in the urine at a follow
      up of 6 months from the operation; there was also a significant increase in the
      Ni blood concentration at the 7 day checkup. The study cohort did not show any
      modification in the frequency of markers of chromosomal damage in the peripheral
      lymphocytes at any of the observation times. The amount of the SCEs and Mni
      recorded at all the observation times did not correlate with each other or with
      any of the ion levels measured in the blood and in the urine.

PMID- 14598403
TI  - Biological response to wear debris generated in carbon based composites as
      potential bearing surfaces for artificial hip joints.
AB  - UHMWPE wear particles have been implicated in osteolysis, implant loosening, and
      long-term failure of total hip arthroplasties in vivo. This study examined four
      carbon-based composite materials as alternatives for UHMWPE in joint bearings.
      These materials were HMU-CVD, SMS-CVD, P25-CVD, and CFR-PEEK. New bearing
      materials should satisfy certain criteria: they should have good wear properties
      that at least match UHMWPE, and produce wear particles with low levels of
      biological activity. Of the four materials tested in multidirectional pin-on
      plate tribological tests, SMS-CVD, P25-CVD, and CFR-PEEK showed lower volumetric
      wear factors than UHMWPE. P25-CVD had the lowest wear factor of 0.54 +/- 0.34 x
      10(-7) mm(3)/Nm. Analysis of P25-CVD wear particles by transmission electron
      microscopy showed that the debris was very small, with the vast majority of
      particles being under 100 nm in size, which was similar in size to metal wear
      particles. The P25-CVD particles were isolated and cultured with L929 fibroblasts
      and U937 monocytic cells to assess their effect on cell viability. P25-CVD
      particles were significantly less cytotoxic (p < 0.01, ANOVA) to both cell types
      than CoCr metal wear particles. This work suggests that carbon-carbon composite
      materials may have potential for use in total hip replacement bearings. Of the
      materials tested P25-CVD had the lowest wear factor, and produced very small wear
      debris that had minimal cytotoxic effect on L929 and U937 cells in vitro.
      Therefore carbon-carbon composites, such as P25-CVD, may be important in the
      development of next-generation implants with lower wear rates and reduced
      cytotoxic potential.

PMID- 14598404
TI  - Static-dynamic friction transition of FRP esthetic orthodontic wires on various
      brackets by suspension-type friction test.
AB  - A new testing apparatus for the measurement of frictional properties was designed
      and the frictional coefficients were obtained and compared with each other in
      various combinations of brackets and orthodontic wires, including esthetic fiber
      reinforced plastic (FRP) wire that was especially designed and manufactured.
      Three kinds of wires (stainless steel, nickel-titanium, and FRP) and four
      brackets (single-crystal alumina, polycrystalline alumina, polycarbonate, and
      stainless steel) were used. The testing was done under dry and wet conditions.
      The friction testing equipment was designed to attach the bracket to a C-shaped
      bar suspended with a variable mass, and sliding along a fixed wire. The
      transition between static and dynamic friction was measured as a breakaway force,
      with the use of a universal test machine. In addition to material properties,
      this testing fixture eliminates geometrical factors, such as the rotational
      moment at the edge of the bracket slot, deflection of the orthodontic wire, and
      tension of the ligature wire. Nearly ideal frictional properties between
      materials are obtained. The frictional properties of FRP wire were similar to
      those of metal wires on all brackets, except the polycrystalline alumina bracket.
      The frictional coefficient between the polycrystalline ceramic bracket and FRP
      wire was larger than that of other combinations. There was little difference in
      frictional coefficients between dry and wet conditions.

PMID- 14598405
TI  - Effects of machined/turned, TiO2-blasted and sandblasted/acid-etched titanium
      oral implant surfaces on nerve conduction: a study on isolated rat sciatic
      nerves.
AB  - The purpose of this study was to explore the clinical relevance of the effects of
      machined/turned, TiO(2)-blasted and sandblasted/acid-etched titanium oral implant
      surfaces on nerve conduction. Isolated rat sciatic nerves were placed between two
      suction electrodes in a pyrex bath containing a tyrode solution. Evoked compound
      action potentials (cAPs) of the nerves were recorded before and after contact
      with the implants. The mandibular incisors of randomly selected animals were
      extracted and changes in cAP amplitudes were used as controls. The differences in
      final cAP values of Astra Tech implants and rat natural teeth were insignificant
      (P < 0.05), whereas the differences between other groups were significant (P <
      0.05). Machined/turned-surface implants did not cause any change in cAPs. A
      slight decrease in cAPs was observed for TiO(2)-blasted and sandblasted/acid
      etched implants, and the natural teeth. The reductions of cAPs in latter groups
      were not 50% after an application time of 300 min. The cAP changes of nerves
      contacting TiO(2)-blasted and sandblasted/acid-etched oral implants fall within
      physiologic limits in vitro. Machined/turned, TiO(2)-blasted, and
      sandblasted/acid-etched titanium implant surfaces do not lead to irreversible
      neurotoxic effects.

PMID- 14598406
TI  - Laparoscopic live donor nephrectomy.

PMID- 14598407
TI  - Patient to surgeon infections--fact or fiction.

PMID- 14598408
TI  - Carcinoid tumour of the appendix.
AB  - BACKGROUND: Appendiceal carcinoid tumours are found in 0.3-0.9 per cent of
      patients undergoing appendicectomy. Controversy exists over the management
      following appendicectomy, especially with regard to the role of right
      hemicolectomy in patients with tumours smaller than 2 cm in diameter. METHODS AND
      RESULTS: The literature pertaining to the behaviour of appendiceal carcinoids was
      reviewed in order to formulate indications for right hemicolectomy. Metastatic
      disease from appendiceal carcinoids is a rare occurrence, but is more common when
      lesions are larger than 2 cm in diameter. The risk-benefit balance of right
      hemicolectomy needs to be better defined, and an improved understanding of tumour
      cell biology may aid prognostic accuracy and decision-making. CONCLUSION: There
      is limited evidence on which to base clear indications for right hemicolectomy in
      patients with a diagnosis of appendiceal carcinoid. Acceptable indications are
      carcinoids larger than 2 cm in size, any high-grade malignant carcinoid
      (including those with a high mitotic index), mesoappendiceal invasion, lesions at
      the base of the appendix with tumour-positive margins, and goblet cell
      adenocarcinoid tumours.

PMID- 14598409
TI  - Laparoscopic donor nephrectomy.
AB  - BACKGROUND: Living kidney donation represents an important source of organs for
      patients with end-stage renal failure. Over the past decade, laparoscopic donor
      nephrectomy has replaced the conventional open procedure in many transplant
      centres. Using evidence-based methods, this study examines the current status of
      laparoscopic donor nephrectomy. METHOD: A Medline literature search (PubMed
      database, 1999-2002) and manual cross-referencing were performed to identify all
      articles relating to laparoscopic donor nephrectomy. Safety and efficacy criteria
      were analysed systematically for each study. Studies included were categorized
      using an evidence-based level grading system. RESULTS: Of 687 publications, 20
      studies with level I-II evidence and 12 with level III evidence were analysed.
      Only one level I study could be identified. Level I and level II evidence
      suggests superiority of the laparoscopic approach in regard to postoperative
      analgesic consumption, hospital stay and return to work. Other safety and
      efficacy criteria, including donor and recipient outcomes, were similar between
      the two techniques. CONCLUSION: Laparoscopic donor nephrectomy has gained
      community acceptance by physicians and patients over the past decade. Despite a
      lack of strong evidence, such as large prospective randomized studies,
      laparoscopic donor nephrectomy is likely to become the 'gold standard' for donor
      nephrectomy in the near future.

PMID- 14598410
TI  - Meta-analysis to determine the incidence of obstetric anal sphincter damage.
AB  - BACKGROUND: The reported incidence of anal sphincter injury after first (11.5
      35.0 per cent) and subsequent (3.4-12.1 per cent) vaginal deliveries varies
      widely. In addition, the reported incidence of associated faecal incontinence
      ranges from zero to 68.2 per cent. The aim of this study was to perform a meta
      analysis of reported incidences of postpartum anal sphincter defect diagnosed by
      endoanal ultrasonography (EAUS) and associated incidences of faecal incontinence.
      METHODS: A Medline search yielded five studies with more than 100 subjects who
      underwent EAUS after childbirth for evaluation of anal sphincter disruption and
      who were questioned about symptoms of faecal incontinence, defined as any
      impairment in flatus and stool control but not including urgency of defaecation.
      A Bayesian meta-analysis was performed to produce one inference while accounting
      for potential heterogeneity among the five study populations. RESULTS: Meta
      analysis of 717 vaginal deliveries revealed a 26.9 per cent incidence of anal
      sphincter defect in primiparous women and an 8.5 per cent incidence of new
      sphincter defects in multiparous women. Overall, 29.7 per cent of anal sphincter
      defects were symptomatic. Some 3.4 per cent of women experienced postpartum
      faecal incontinence without an anal sphincter defect. In a Bayesian calculation,
      the probability of postpartum faecal incontinence due to a sphincter defect was
      76.8-82.8 per cent. CONCLUSION: : The incidence of occult anal sphincter
      disruption following vaginal delivery is much higher than commonly estimated.
      However, at least two-thirds of occult defects are asymptomatic postpartum. The
      probability of faecal incontinence associated with an anal sphincter defect was
      76.8-82.8 per cent.

PMID- 14598411
TI  - Randomized clinical trial of intermittent pneumatic compression and low molecular
      weight heparin in trauma.
AB  - BACKGROUND: After trauma, up to 60 per cent of immobilized patients have been
      reported to develop a silent deep vein thrombosis (DVT). No large, prospective
      randomized trials have tested the efficacy of intermittent pneumatic compression
      (IPC) devices in these patients. METHODS: A prospective randomized trial was
      performed of 442 patients who received thromboprophylaxis using either an IPC
      device or low molecular weight heparin (LMWH). Duplex imaging was performed on
      both legs on admission, and was repeated weekly thereafter until discharge, at 30
      days or when there was a thrombotic event, whichever occurred first. RESULTS:
      There were no significant differences in time spent in intensive care, or the
      proportion of patients with pelvic fractures, spinal cord or head injuries
      between the two groups. Six patients (2.7 per cent) developed a DVT in the IPC
      group and one (0.5 per cent) in the LMWH group (P = 0.122). Pulmonary embolism
      occurred in one patient in each group. There were 13 minor bleeding episodes
      (four in the IPC group and nine in the LMWH group) and eight major bleeding
      episodes (four in each group), none of which required operative intervention.
      CONCLUSION: The low rate of thromboembolic complications and the cost savings
      suggest that IPC might be used safely and effectively for thromboprophylaxis in
      trauma patients.

PMID- 14598412
TI  - Randomized clinical trial of laparoscopic cholecystectomy performed with mini
      instruments.
AB  - BACKGROUND: The outcomes after traditional laparoscopic cholecystectomy (LC; one
      10-mm port, one 12-mm port and two 5-mm ports) and minilaparoscopic
      cholecystectomy (MLC; three 3-mm ports and one 12-mm port) for gallstone disease
      were compared. METHODS: The study was a randomized, single-blind trial comparing
      LC with MLC. Only elective patients were eligible for inclusion. LC was a routine
      procedure at the institution in which the study was performed, whereas MLC was
      introduced after a short training period. The randomization period was from
      January to December 2001. RESULTS: Of 175 patients who had elective minimal
      access cholecystectomy during the randomization period, 135 entered the trial: 68
      underwent LC and 67 underwent MLC. The groups were matched for age, sex and
      preoperative characteristics. Median (range) operating times for LC and MLC were
      similar (45 (20-120) and 50 (20-170) min respectively). Intraoperative and
      postoperative complication rates, the time for the patient to resume walking,
      eating and passing stools, and median hospital stay were the same in the two
      groups. The level of postoperative pain was lower in the MLC group at 1 h (P =
      0.011), 3 h (P = 0.012), 6 h (P = 0.003), 12 h (P = 0.052) and 24 h (P = 0.034).
      Patients who had MLC received fewer injections of analgesic (P = 0.036) and more
      patients in this group expressed satisfaction with the cosmetic result (P =
      0.001). CONCLUSION: MLC took a similar time to perform and caused less
      postoperative pain than the standard laparoscopic procedure. Reducing the port
      size further enhanced the advantages of laparoscopic over open cholecystectomy.

PMID- 14598413
TI  - Removal of two sentinel nodes accurately stages the axilla in breast cancer.
AB  - BACKGROUND: Assessment of lymph node status in breast cancer is still necessary
      for staging. Sentinel lymph node biopsy (SNB) may provide accurate staging with
      less morbidity than axillary clearance. The aim of this study was to assess the
      effect of the number of sentinel nodes removed on the false-negative rate.
      METHODS: Data were collected prospectively from 395 women undergoing SNB for
      breast cancer, between June 1995 and December 2001. All nodes that were hot
      and/or blue were removed and analysed. RESULTS: During this interval 136 patients
      who had SNB were lymph node positive. The median number of sentinel nodes removed
      was two (range one to five). The overall false-negative rate of SNB in these
      women was 7.1 per cent. If only one sentinel node had been removed, the false
      negative rate would have been 16.5 per cent. The removal of more than two nodes
      had no effect on axillary staging in all but two women. CONCLUSION: In early
      breast cancer, when there were multiple sentinel nodes, removal of two sentinel
      nodes significantly reduced the false-negative rate compared with removal of one
      node. Removing more than two sentinel nodes did not significantly reduce the
      false-negative rate further.

PMID- 14598414
TI  - Prediction of tumour involvement in remaining axillary lymph nodes when the
      sentinel node in a woman with breast cancer contains metastases.
AB  - BACKGROUND: In a significant proportion of women with breast cancer, the sentinel
      node is the only involved node in the axilla. The purpose of this study was to
      identify factors associated with histologically positive non-sentinel lymph
      nodes. METHODS: Between 1997 and 2002, 800 women with early breast cancer
      underwent sentinel node biopsy. In 263 patients the node contained metastases,
      including 83 with micrometastases detected by immunohistochemistry (IHC), 40
      micrometastases detected on haematoxylin, eosin and safranine (HES) staining, and
      140 macrometastases. All clinical and histological criteria were recorded and
      analysed with reference to histology of the non-sentinel node. RESULTS: The risk
      of metastasis in the non-sentinel lymph node was related to the volume of the
      tumour in the sentinel node. Non-sentinel nodes were involved in five (6.0 per
      cent) of 83 women when the sentinel node contained only micrometastatic cells
      detected on IHC, and in three (7.5 per cent) of 40 women when micrometastases
      were detected by HES, compared with 55 (39.3 per cent) of 140 when the sentinel
      node contained macrometastases on HES staining. Univariate analysis revealed a
      significant association between non-sentinel node involvement and type of
      metastasis within the sentinel node, clinical primary tumour size, palpable
      axillary lymph nodes before operation, pathological primary tumour size and the
      presence of peritumoral lymphovascular invasion. On multivariate analysis, the
      type of metastasis within the sentinel node (P < 0.001), histological tumour size
      greater than 20 mm (P = 0.017) and the presence of palpable axillary nodes before
      operation (P = 0.014) remained significant. CONCLUSION: Clinical and pathological
      factors associated with sentinel node histology can reliably predict women for
      whom further axillary clearance is recommended, but it is not yet possible to
      determine a subgroup of patients in whom the sentinel node is the only involved
      node and for whom further axillary treatment may be unnecessary.

PMID- 14598415
TI  - Abdominal aortic aneurysms in the New Zealand Maori population.
AB  - BACKGROUND: Abdominal aortic aneurysm (AAA) is believed to be a rare disease in
      people of non-European descent. Maori, New Zealand's indigenous people, are
      thought to originate from South East Asia, so their incidence of AAA might also
      be expected to be low. The aim was to investigate the incidence and phenotypic
      factors associated with AAA in the New Zealand Maori population. METHODS: A
      retrospective study was performed using the audit database of the New Zealand
      Society of Vascular Surgeons. Age-standardized rates of admission and death were
      calculated for Maori and non-Maori. RESULTS: Maori comprised 3.9 per cent of the
      population who had an AAA repaired, similar to the percentage of the Maori
      population aged over 65 years. However, the death rate from AAA in Maori was 2.4
      times the rate in non-Maori. Maori were younger at diagnosis than non-Maori (65.2
      versus 71.8 years; P < 0.001), had more emergency procedures (46.6 versus 30.2
      per cent; P = 0.018) and a significantly higher proportion of Maori admissions
      were for a ruptured aneurysm. CONCLUSION: Maori had a higher mortality rate from
      AAA than non-Maori New Zealanders. Although admission rates between Maori and non
      Maori were similar, the earlier age of onset and the increased proportion of
      ruptured aneurysms may indicate that the disease is more severe in Maori.

PMID- 14598416
TI  - Value of endoscopic ultrasonography as a predictor of long-term survival in
      oesophageal carcinoma.
AB  - BACKGROUND: : Endoscopic ultrasonography (EUS) is considered to be the best
      locoregional staging technique for cancer of the oesophagus. This study evaluated
      the relationship between preoperative EUS findings, completeness of surgical
      resection and survival. METHODS: : Between January 1995 and July 2002, 150
      patients who underwent EUS for staging of tumours of the oesophagus were analysed
      prospectively. All underwent surgical resection with curative intent without
      neoadjuvant treatment. RESULTS: : Patient survival was significantly related to
      tumour (EUS T), node (EUS N) and Union Internacional Contra la Cancrum
      classification (EUS UICC) stage according to sonographic findings (P = 0.003, P =
      0.009 and P = 0.004 respectively), and the presence of stenosis determined by EUS
      (P = 0.004). EUS T stage was a prognostic factor for survival (relative risk 1.7
      (95 per cent confidence interval (c.i.) 1.1 to 3.0); P = 0.046). Complete
      surgical resection (R0) was also significantly related to EUS T, N and UICC
      classification (P < 0.001). EUS UICC stage was a factor predictive of R0
      resection (relative risk 2.6 (95 per cent c.i. 1.4 to 4.8); P = 0.003).
      CONCLUSION: : R0 resection and survival of patients with tumours of the
      oesophagus were strongly related to endosonographic findings. These results
      support the proposal that EUS should be performed in all patients with
      oesophageal cancer, not only for staging patients before therapy but also to
      determine prognosis.

PMID- 14598417
TI  - Effect of neoadjuvant chemoradiotherapy on angiogenesis in oesophageal cancer.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) levels are raised in the
      serum of patients with oesophageal carcinoma. The aim of this study was to
      evaluate the tumour microvasculature and the role of tumour-associated
      macrophages in VEGF production after neoadjuvant chemoradiotherapy and surgery
      for oesophageal cancer. METHODS: Sections from 92 consecutively resected
      oesophageal tumours were stained for VEGF, von Willebrand factor and CD68. Twenty
      seven patients received preoperative chemoradiation and 65 underwent surgical
      excision alone. The cellular source of VEGF was determined by parallel-section
      staining. Microvessel density and macrophage count were determined for each
      tumour by means of image analysis software. RESULTS: There were no significant
      differences between the two groups in age, sex or tumour type. Local downstaging
      of disease was evident in most specimens of tumours that had received
      preoperative chemoradiation. All tumours stained positive for VEGF, including
      those demonstrating a complete pathological response. Staining of parallel
      sections confirmed macrophages as the principal source of VEGF. Mean microvessel
      density was 6.4 per high-power field (h.p.f.) in tumours that received
      preoperative chemoradiation compared with 5.3 per h.p.f. in those treated by
      surgery alone (P = 0.130). A significant increase in tumour-associated macrophage
      infiltration was noted in tumours treated with neoadjuvant chemoradiation (22.1
      per h.p.f.) compared with those treated by surgery alone (14.3 per h.p.f.) (P =
      0.042). CONCLUSION: Preoperative chemoradiation had little effect on the local
      angiogenic profile of the tumour in patients with oesophageal cancer. Tumour
      infiltrating macrophages seem to be the source of persistent VEGF production
      after chemoradiotherapy and might explain the raised serum levels. Addition of an
      antiangiogenic agent to this regimen may be worthwhile in patients with
      oesophageal carcinoma.

PMID- 14598419
TI  - Plasminogen mediates liver regeneration and angiogenesis after experimental
      partial hepatectomy.
AB  - BACKGROUND: Plasmin system components are upregulated after partial hepatectomy,
      but their contribution to surgery-induced hepatic angiogenesis and regeneration
      is unclear. Liver regeneration and angiogenesis after partial hepatectomy were
      examined in mice lacking plasminogen or urokinase plasminogen activator (uPA).
      METHODS: Mice with a single-gene deletion of plasminogen or uPA were subjected to
      70 per cent partial hepatectomy. Liver regeneration was measured as relative
      liver weight and cell proliferation index. Angiogenesis was quantified by
      determining hepatic microvessel density after staining for sinusoidal endothelial
      cells. RESULTS: The liver remnant weight was significantly reduced in mice
      lacking plasminogen or uPA compared with that in wild-type mice on days 2 and 7
      after partial hepatectomy. This correlated with impaired cell proliferation. In
      wild-type mice, regeneration was accompanied by a significant increase in
      microvessel density after hepatectomy; this increase was impaired in plasminogen
      deficient mice. CONCLUSION: Plasminogen and uPA are essential for optimal liver
      regeneration. In addition, plasminogen appears to be a major determinant in
      regeneration-associated hepatic angiogenesis.

PMID- 14598418
TI  - Preoperative treatment of hepatocellular carcinoma with intra-arterial injection
      of 131I-labelled lipiodol.
AB  - BACKGROUND: Recurrence is common after surgery for hepatocellular carcinoma
      (HCC). METHODS: The efficacy of, and tolerance to, preoperative intra-arterial
      injection of (131)I-labelled lipiodol was examined in 34 patients with HCC,
      including 29 with cirrhosis. Twenty-five patients had a single hepatic tumour and
      the mean(s.d.) tumour size was 5.2(3.7) (range 2-15) cm. The patients received
      between one and three injections of (131)I-labelled lipiodol (60 mCi per
      injection) before surgery. Operations included 14 liver transplants, 13 minor
      hepatectomies, six major hepatectomies and one exploratory laparotomy. RESULTS:
      There was one complication after lipiodol injection due to acute ischaemia of the
      small bowel. Three of 34 patients died within 28 days, two after transplantation
      and one after resection. An objective tumour response (decrease in tumour size)
      was observed in 19 of 34 patients, and a complete histological response in eight
      of 34. There was an objective tumour response or major histological necrosis of
      lesions in 25 of 34 patients. The 5-year survival rate was 48.4(8.0) per cent,
      69.0 per cent after transplantation and 36.0 per cent in patients who underwent
      resection. CONCLUSION: This preoperative method appeared to be well tolerated,
      and provided promising results in terms of macroscopic and microscopic tumour
      responses.

PMID- 14598420
TI  - Isolated hepatic perfusion with high-dose melphalan for the treatment of
      colorectal metastasis confined to the liver.
AB  - BACKGROUND: Isolated hepatic perfusion (IHP) involves complete vascular isolation
      of the liver to allow treatment with doses that would be toxic if delivered
      systemically. A phase II study of IHP in patients with colorectal metastases
      confined to the liver was performed. METHODS: Seventy-three patients with
      irresectable colorectal metastases underwent IHP with high-dose melphalan (200
      mg) for 1 h. Toxicity was graded according to the National Cancer Institute
      Common Toxicity Criteria and tumour response was assessed according to World
      Health Organization criteria. RESULTS: Seventy-one patients were perfused
      according to the protocol. Four patients died within 30 days after IHP, resulting
      in an operative mortality rate of 5.6 per cent. Sixteen patients (22.5 per cent)
      experienced grade 3-4 hepatotoxicity 1 week after IHP, which was transient and
      resolved within 3 months in all patients. The tumour response rate (complete or
      partial remission) was 59 per cent. Median time to progression was 7.7 (range 2.3
      31.4) months. Overall median survival after IHP was 28.8 months with a 3-year
      survival rate of 37 per cent. CONCLUSION: IHP for irresectable colorectal
      metastases confined to the liver resulted in good response rates and long-term
      survival in a selected group of patients.

PMID- 14598421
TI  - Role of postoperative computed tomography in patients with severe liver injury.
AB  - BACKGROUND: The role of postoperative computed tomography (CT) in asymptomatic
      patients with severe liver injury has not been investigated. The aim of the
      present study was to investigate the nature and incidence of significant liver
      related abnormalities detected by postoperative CT in asymptomatic patients with
      severe liver injury. METHODS: This was a prospective study of survivors with
      severe liver injury (grades III-V) who were treated surgically. The patients
      underwent CT to evaluate the liver after operation, irrespective of symptoms.
      RESULTS: During the study interval there were 181 patients with severe liver
      injury, of whom 49 fulfilled the criteria for inclusion. The overall incidence of
      liver-related complications detected by CT was 49 per cent (necrotic areas in the
      liver in seven patients, seven bilomas, four abscesses, three perihepatic
      collections and three false aneurysms). In the subgroup of 17 asymptomatic
      patients CT revealed four abnormalities: two large bilomas, one false aneurysm
      and one fluid collection. Two of these patients required therapeutic intervention
      and the other two remained under observation. CONCLUSION: In view of the
      incidence of asymptomatic significant liver abnormalities following operative
      management of severe liver injury, it is recommended that these patients undergo
      routine postoperative CT.

PMID- 14598422
TI  - Duodenum- and spleen-preserving total pancreatectomy for end-stage chronic
      pancreatitis.
AB  - BACKGROUND: Total pancreatectomy may be warranted in patients with advanced
      chronic pancreatitis in whom partial resection has failed and in those with end
      stage pancreatic function. A new operation, duodenum- and spleen-preserving total
      pancreatectomy, is described. METHODS: Nineteen consecutive patients with chronic
      pancreatitis who had duodenum- and spleen-preserving total pancreatectomy were
      studied. RESULTS: There were 15 men and four women with a median age of 40 (range
      29-64) years. The aetiology was alcohol misuse in nine, hereditary pancreatitis
      in five and idiopathic in five patients. All patients had chronic intractable
      abdominal pain. Six had undergone pancreatic surgery previously and one had had
      multiple coeliac plexus blocks. There were ten postoperative complications in
      five patients, and one hospital death. The median hospital stay was 25 (range 10
      84) days. There was a reduction in pain (P < 0.001) and analgesic use (P < 0.001)
      after surgery, and weight gain was noted at 12 and 24 months (P < 0.001). Nine
      patients required readmission to hospital, four because of surgical
      complications: adhesional obstruction in one, biliary stricture in two and
      duodenal obstruction in one. In the other five patients (four of whom had long
      standing pre-existing diabetes mellitus) readmission was for better control of
      pain (three patients), diabetes mellitus (two), and diabetes-associated diarrhoea
      (two) or gastropathy (one). CONCLUSION: Duodenum- and spleen-preserving total
      pancreatectomy has a role in selected patients with medically intractable pain
      from chronic pancreatitis.

PMID- 14598423
TI  - Percutaneous transhepatic choledochoscopic removal of intrahepatic stones.
AB  - BACKGROUND: Treatment of hepatolithiasis is complex and difficult. With the
      advent of biliary endoscopy and radiological intervention, percutaneous
      choledochoscopic removal of intrahepatic stones has become a well established
      procedure. METHODS: Seventy-nine patients with intrahepatic stones that were
      removed by percutaneous transhepatic choledochoscopy (PTCS) between 1993 and 2001
      were studied retrospectively. The results of the procedure and the long-term
      outcome of these patients were analysed. RESULTS: The success rate of
      choledochoscopic removal of intrahepatic stones was 76.8 per cent. Complications
      occurred in 17 patients (21.5 per cent). Removal of stones predominantly on the
      right side was difficult using this method. Cholangitis occurred in about one
      third of patients within 3-5 years after PTCS. For patients with a stricture,
      cholangitis recurred gradually over the years of follow-up. CONCLUSION:
      Intrahepatic stricture was the major determinant for the recurrence of stones or
      symptoms. Hepatic resection should be offered to these patients if the disease is
      localized in one liver segment or lobe. In other cases, percutaneous
      choledochoscopy and stricture dilatation is a useful solution, and may reduce
      further damage to the liver.

PMID- 14598424
TI  - Use of a continent colonic conduit for treatment of refractory evacuatory
      disorder following construction of an electrically stimulated gracilis neoanal
      sphincter.
AB  - BACKGROUND: This study reports the outcome from the addition of a continent
      colonic conduit (CCC) to an electrically stimulated gracilis neoanal sphincter in
      patients with severe evacuatory disorder following formation of a neosphincter
      for end-stage faecal incontinence. METHODS: One hundred and twenty patients had
      an electrically stimulated gracilis neoanal sphincter constructed for end-stage
      faecal incontinence. Seven patients developed severe evacuatory disorders;
      construction of a CCC was required in six patients and an antegrade continence
      enema procedure in one. RESULTS: Median follow-up of the seven patients was 77
      (range 6-96) months. Six patients with evacuatory disorders had a successful
      outcome, defined as continence to solid and liquid stool as well as correction of
      the evacuatory disorder. A stoma was formed in one patient. Patients who had
      previously undergone anorectal reconstructive surgery were more likely to develop
      an evacuatory disorder following construction of an electrically stimulated
      gracilis neoanal sphincter than patients operated on for other reasons (chi2 =
      28.13, 1 d.f., P < 0.001). CONCLUSION: Construction of a CCC is a useful
      technique for the majority of patients with severe evacuatory disorders following
      the formation of an electrically stimulated gracilis neoanal sphincter, for whom
      the only alternative would be an end stoma. A CCC may be incorporated with
      construction of an electrically stimulated gracilis neoanal sphincter in patients
      at significant risk of postoperative severe evacuatory disorders.

PMID- 14598425
TI  - Prognostic value of preoperative magnetic resonance imaging of the pelvis in
      rectal cancer.
AB  - BACKGROUND: Despite radiotherapy and improved surgical techniques, local
      recurrence rates after treatment of rectal cancer still vary between 3 and 30 per
      cent. Tumour involvement of the circumferential resection margin (CRM) predicts a
      high risk of local recurrence. Magnetic resonance imaging (MRI) allows accurate
      description of the tumour and its spread within the mesorectum. The aim of this
      study was to assess the prognostic impact of an involved CRM identified at
      preoperative MRI in patients with rectal cancer. METHODS: Preoperative MRI was
      performed in 115 patients with rectal cancer between 1995 and 1999. The images
      were evaluated retrospectively. The shortest distance from the tumour to the CRM
      was measured, correlated with patient outcome and compared with histopathological
      findings. RESULTS: The risk of any recurrence in patients with or without a
      tumour-involved margin on MRI was nine of 29 and nine of 57 respectively (P =
      0.036). Overall survival at 5 years was 43 and 77 per cent (P = 0.012)
      respectively. Twenty-four of 30 patients who had an involved CRM on
      histopathology were correctly identified by MRI. CONCLUSION: Patients with a
      potentially involved CRM identified by MRI had a significantly higher risk of
      recurrence and cancer-related death. Preoperative MRI may be of prognostic value
      in rectal cancer and may be used to select patients for neoadjuvant
      radiochemotherapy and/or more radical surgery.

PMID- 14598426
TI  - Comparison of stenting with emergency surgery as palliative treatment for
      obstructing primary left-sided colorectal cancer.
AB  - BACKGROUND: Self-expanding metallic stents provide an alternative to surgery as
      definitive palliation in patients with obstructing colorectal cancer. This study
      aimed to compare the outcome of patients with obstruction due to primary left
      sided colorectal cancer treated by palliative stenting with outcome in patients
      who had undergone surgery. METHODS: Patients with incurable obstructing primary
      colorectal cancer distal to the splenic flexure treated with emergency surgery (n
      = 31) or placement of a metallic stent (n = 30) from November 1997 to June 2002
      were included. Data on the mortality, morbidity, necessity of intensive care and
      hospital stay for the two groups were compared. The subsequent outcomes,
      including the incidence of stoma creation and survival, were also analysed.
      RESULTS: The two groups were similar in terms of age, sex distribution and
      presence of co-morbidity. Insertion of metallic stents was successful in 29 of 30
      patients. Hospital death occurred in four and eight patients in the study and
      control groups respectively (P = 0.335). Fewer patients with placement of a stent
      required intensive care (1 versus 11; P = 0.001) and the median hospital stay was
      shorter in patients with stenting (4 versus 8 days; P = 0.008). A stoma was
      subsequently created in four patients with stenting, whereas 15 patients who had
      emergency operation required a stoma (P = 0.005). The difference in median
      survival between the two groups was not statistically significant (107 versus 119
      days; P = 0.088). CONCLUSION: Self-expanding metallic stents are effective in the
      palliation of obstructing colorectal cancer. Placement of stents is associated
      with a shorter hospital stay, less likelihood of intensive care and a lower
      incidence of stoma creation, when compared with emergency surgery. Thus insertion
      of a metallic stent should be considered in patients with incurable obstructing
      colorectal cancer.

PMID- 14598427
TI  - Ileal pouch-vaginal fistula treated by abdominoanal advancement of the ileal
      pouch.

PMID- 14598428
TI  - Prognostic factors in resection of pulmonary metastasis from colorectal cancer.
AB  - BACKGROUND: The aim of this retrospective study was to evaluate characteristics
      of primary colorectal cancer and pulmonary metastases in order to identify
      prognostic factors for overall survival and risk factors for further
      intrapulmonary recurrence after resection of pulmonary metastases from colorectal
      cancer. METHODS: Forty-nine patients who underwent resection of pulmonary
      metastases from colorectal cancer were reviewed. The factors assessed were age,
      sex, pathological findings of the original colorectal cancer (depth, lymphatic
      invasion, venous invasion, lymph node metastasis, differentiation, Dukes' stage)
      and pulmonary metastasis (maximum tumour size, number of tumours, completeness of
      resection), serum carcinoembryonic antigen level, previous hepatectomy for liver
      metastases, and surgical procedure for resection of pulmonary metastasis. Overall
      survival and intrapulmonary recurrence were also reviewed. RESULTS: Survival
      rates after resection of pulmonary metastases were 78 per cent at 3 years and 56
      per cent at 5 years. Solitary pulmonary metastases were significantly correlated
      with survival (P = 0.049). The pathological features of the primary colorectal
      cancer had no impact on survival. Histologically incomplete resection of
      pulmonary metastasis significantly correlated with pulmonary re-recurrence (P =
      0.034). CONCLUSION: Long-term survival can be expected after complete resection
      of pulmonary metastases arising from colorectal cancer, especially in patients
      with a solitary pulmonary metastasis.

PMID- 14598429
TI  - Population-based study of the surgical workload and economic impact of bowel
      obstruction caused by postoperative adhesions.
AB  - BACKGROUND: Intestinal obstruction is the most severe consequence of adhesion
      formation. This study examined the annual surgical workload and costs of
      intestinal obstruction caused by postoperative intra-abdominal adhesions.
      METHODS: The study was a retrospective case-note review of patients hospitalized
      for intestinal obstruction caused by postoperative adhesions in a well defined
      geographical area. The surgical workload and direct costs of inpatient care were
      analysed. RESULTS: There were 138 admissions for postoperative adhesion-related
      intestinal obstruction during the study with a total of 1118 inpatient days. The
      median hospital stay was 4 (range 1-58) days among patients who had non-operative
      treatment and 11 (range 2-34) days for those who had surgery. Surgery was
      necessary in 40 patients (29.0 per cent). The mean operating time (time from skin
      incision to last stitch) and the mean time spent in the operating theatre were 79
      and 141 min respectively. The cumulative operating time for the surgical group
      was 52 h 20 min and the cumulative theatre time was 93 h 44 min. The annual
      direct hospital cost for postoperative adhesional intestinal obstruction was
      pound 181 653 in the district studied and the estimated cost for the whole of
      Finland was pound 2 077 796. CONCLUSION: This population-based study indicates
      that the workload and costs associated with bowel obstruction caused by
      postoperative adhesions are substantial.

PMID- 14598430
TI  - Sequential physiology scoring facilitates objective assessment of resuscitation
      in patients with an intra-abdominal emergency.
AB  - BACKGROUND: Patients who present with an intra-abdominal emergency often require
      urgent surgery. Before surgery a period of resuscitation is undertaken pre
      emptively, or to correct any overt physiological derangement. The assessment of
      response to resuscitation and the decision when to operate is subjective. This
      study examined the role of sequential physiology scores in assessing the response
      to resuscitation objectively. METHODS: Sequential physiology scores were recorded
      in 92 patients with abdominal pathology that subsequently required urgent or
      emergency surgery. The physiology component of the Physiological and Operative
      Severity Score for enUmeration of Mortality and morbidity (POSSUM), Acute
      Physiology And Chronic Health Evaluation (APACHE) II and III, and Simplified
      Acute Physiology Score (SAPS) II were determined at presentation, during
      resuscitation and immediately before surgery. RESULTS: There were 76 survivors;16
      patients died. All scoring systems showed an improvement during resuscitation but
      subsequent deterioration before surgery. The POSSUM, and APACHE II and III
      physiology scores differentiated more effectively between survivors and patients
      who died than SAPS II. CONCLUSION: Sequential physiology scores may facilitate
      the assessment of patients' response to resuscitation. Patients who fail to
      respond to resuscitation when identified may benefit from more expedient surgery.

PMID- 14598431
TI  - Cold provocation testing and hand-arm vibration syndrome--an audit of the results
      of the Department of Trade and Industry for the evaluation of miners (Br J Surg
      2003; 90: 1076-1079).

PMID- 14598432
TI  - Cold provocation testing and hand-arm vibration syndrome--an audit of the results
      of the Department of Trade and Industry for the evaluation of miners (Br J Surg
      2003; 90: 1076-1079).

PMID- 14598433
TI  - Sentinel lymph node mapping in colorectal cancer (Br J Surg 2003; 90: 659-667).

PMID- 14598434
TI  - Accuracy of fine-needle aspiration cytology in patients with radiation-induced
      thyroid neoplasms (Br J Surg 2003; 90: 755-758).

PMID- 14598435
TI  - Temporary closure of open abdominal wounds by the modified sandwich-vacuum pack
      technique (Br J Surg 2003; 90: 718-722).

PMID- 14598437
TI  - Randomized clinical trial comparing consultant-led or open access investigation
      for large bowel symptoms (Br J Surg 2003; 90: 941-947).

PMID- 14598436
TI  - Role of neoadjuvant chemotherapy in the treatment of multiple colorectal
      metastases to the liver (Br J Surg 2003; 90: 963-969).

PMID- 14598439
TI  - Color realism and color science.
AB  - The target article is an attempt to make some progress on the problem of color
      realism. Are objects colored? And what is the nature of the color properties? We
      defend the view that physical objects (for instance, tomatoes, radishes, and
      rubies) are colored, and that colors are physical properties, specifically, types
      of reflectance. This is probably a minority opinion, at least among color
      scientists. Textbooks frequently claim that physical objects are not colored, and
      that the colors are "subjective" or "in the mind." The article has two other
      purposes: First, to introduce an interdisciplinary audience to some distinctively
      philosophical tools that are useful in tackling the problem of color realism and,
      second, to clarify the various positions and central arguments in the debate. The
      first part explains the problem of color realism and makes some useful
      distinctions. These distinctions are then used to expose various confusions that
      often prevent people from seeing that the issues are genuine and difficult, and
      that the problem of color realism ought to be of interest to anyone working in
      the field of color science. The second part explains the various leading answers
      to the problem of color realism, and (briefly) argues that all views other than
      our own have serious difficulties or are unmotivated. The third part explains and
      motivates our own view, that colors are types of reflectances and defends it
      against objections made in the recent literature that are often taken as fatal.

PMID- 14598440
TI  - Convergence of biological and psychological perspectives on cognitive
      coordination in schizophrenia.
AB  - The concept of locally specialized functions dominates research on higher brain
      function and its disorders. Locally specialized functions must be complemented by
      processes that coordinate those functions, however, and impairment of
      coordinating processes may be central to some psychotic conditions. Evidence for
      processes that coordinate activity is provided by neurobiological and
      psychological studies of contextual disambiguation and dynamic grouping.
      Mechanisms by which this important class of cognitive functions could be achieved
      include those long-range connections within and between cortical regions that
      activate synaptic channels via NMDA-receptors, and which control gain through
      their voltage-dependent mode of operation. An impairment of these mechanisms is
      central to PCP-psychosis, and the cognitive capabilities that they could provide
      are impaired in some forms of schizophrenia. We conclude that impaired cognitive
      coordination due to reduced ion flow through NMDA-channels is involved in
      schizophrenia, and we suggest that it may also be involved in other disorders.
      This perspective suggests several ways in which further research could enhance
      our understanding of cognitive coordination, its neural basis, and its relevance
      to psychopathology.

PMID- 14598441
TI  - Metal oxide nanoarchitectures for environmental sensing.
AB  - Metal oxide materials are widely used for gas sensing. Capable of operating at
      elevated temperatures and in harsh environments, they are mechanically robust and
      relatively inexpensive and offer exquisite sensing capabilities, the performance
      of which is dependent upon the nanoscale morphology. In this paper we first
      review different routes for the fabrication of metal oxide nanoarchitectures
      useful to sensing applications, including mesoporous thin films, nanowires, and
      nanotubes. Two sensor test cases are then presented. The first case examines the
      use of highly uniform nanoporous Al2O3 for humidity sensing; we find that such
      materials can be successfully used as a wide-range humidity sensor. The second
      test case examines the use of TiO2 nanotubes for hydrogen sensing. Going from a
      nitrogen atmosphere to one containing 1000 ppm of hydrogen, at 290 degrees C, 22
      nm-diameter titania nanotubes demonstrate a 10(4) change in measured resistance
      with no measurement hysteresis.

PMID- 14598442
TI  - Construction of phi29 DNA-packaging RNA monomers, dimers, and trimers with
      variable sizes and shapes as potential parts for nanodevices.
AB  - Recently, DNA and RNA have been under extensive scrutiny with regard to their
      feasibility as parts in nanotechnology. The DNA-packaging motor of bacterial
      virus phi29 contains six copies of pRNA molecules, which together form a
      hexameric ring as a crucial part of the motor. This ring is formed via hand-in
      hand interaction by Watson-Crick base pairing of four nucleotides from the left
      and right loops. Here we report that this pRNA tends to form a circular ring by
      hand-in-hand contact even when in dimer or trimer form, thus implying that the
      pRNA structure is flexible. Stable dimers and trimers have been formed from the
      monomer unit in a protein-free environment with nearly 100% efficiency. The
      dimers and trimers could be isolated by density gradient sedimentation or
      purified from native gel. Dimers and trimers were resistant to pH levels as low
      as 4 and as high as 10, to temperatures as low as -70 degrees C and as high as 80
      degrees C, and to high salt concentrations such as 2 M NaCl and 2 M MgCl2.
      Further study showed that pRNA dimers or trimers with variable lengths could be
      constructed. Seventy-five bases were found to be the central component in this
      formation. The elongation of RNA at the 3' end up to 120 bases did not hinder
      their formation. Other conditions, including the salt requirement for the
      formation of monomers, dimers, and trimers, have been investigated. RNA monomers,
      dimers, and trimers with variable lengths are potential parts for nanodevices.

PMID- 14598443
TI  - He and N encapsulations in small cages: model computations for possible
      nanotechnology systems.
AB  - Endohedral cage compounds have been considered as possible candidate species for
      molecular memories. In this report, computations are carried out on four
      hypothetical He-containing endohedral systems, He@C14H16 (isogarudane and
      garudane cages) and He@C36 (D6h and D2d cages), and two hypothetical N-containing
      endohedral systems, N@C36 (D6h and D2d cages). Geometry optimizations are
      followed by vibrational analysis in some cases. The geometry optimizations can
      indeed produce local energy minima for the endohedral systems. While in N@C36 D6h
      the nitrogen atom has a central location, in N@C36 D2d it exhibits a bonding
      pattern. Thermodynamic and kinetic stability aspects are also discussed.

PMID- 14598444
TI  - A liftoff technique for molecular nanopatterning.
AB  - For quantum-dot cellular automata molecular electronic devices, one of the
      fundamental tasks is to arrange the molecules on a surface in a controlled
      manner. In this report, we discuss a molecular lift off technique to form
      nanopatterns toward the development of molecular circuits. In our molecular lift
      off technique, we use electron beam lithography to form nano-trenches on a
      polymethylmethacrylate (PMMA) film on a SiO2 wafer. This wafer is soaked in a
      Creutz-Taube ion [(NH3)5Ru(pyrazine)Ru(NH3)5](o-toluenesulfonate)5 (CT5) aqueous
      solution. After residual PMMA removal, atomic force microscopy is used to
      investigate the resulting surface. Thirty-five nanometer CT5 lines are
      demonstrated on a SiO2 surface. Compared with other molecular nanopatterning
      techniques, ours is both economical and capable of high-resolution.

PMID- 14598445
TI  - Effect of elliptical deformation on molecular polarizabilities of model carbon
      nanotubes from atomic increments.
AB  - The interacting induced dipole polarization model implemented in our program
      POLAR is used for the calculation of the dipole-dipole polarizability alpha. The
      method is tested with single-wall carbon nanotube models as a function of
      nanotube radius and elliptical deformation. The results for polarizability follow
      the same trend as reference calculations performed with our version of the
      program PAPID. For the zigzag tubes, the polarizability is found to follow a
      remarkably simple law, that is, it varies as the inverse of the radius. A
      dramatic effect is also found with elliptical deformation. It is found that the
      polarizability and related properties can be modified continuously and reversibly
      by the external radial deformation. These results suggest an interesting
      technology in which mechanical deformation can control chemical properties of the
      carbon nanotubes. POLAR calculations differentiate more effectively than PAPID
      computations among single-wall nanotube models with increasing radial
      deformation. Different effective polarizabilities are calculated for the atoms at
      the highest and lowest curvature sites. POLAR calculations discriminate more
      efficiently than PAPID computations between the effective polarizabilities of the
      highest and lowest curvature sites. This remarkable and significant tunable
      polarizability can have important implications for metal coverage of metals on
      nanotubes and selective adsorption and desorption of foreign atoms and molecules
      on nanotubes and can lead to a wide variety of technological applications, such
      as catalysts, hydrogen storage, magnetic tubes, etc.

PMID- 14598446
TI  - Theoretical analysis of a carbon-carbon dimer placement tool for diamond
      mechanosynthesis.
AB  - Density functional theory is used with Gaussian 98 to analyze a new family of
      proposed mechanosynthetic tools that could be employed for the placement of two
      carbon atoms--a carbon-carbon (CC) dimer--on a growing diamond surface at a
      specific site. The analysis focuses on specific group IV-substituted biadamantane
      tool tip structures and evaluates their stability and the strength of the bond
      they make with the CC dimer. These tools should be stable in a vacuum and should
      be able to hold and position a CC dimer in a manner suitable for positionally
      controlled diamond mechanosynthesis at room temperature.

PMID- 14598447
TI  - Suspended multiwalled carbon nanotubes as self-aligned evaporation masks.
AB  - We describe the nanofabrication study of self-aligned electrodes on suspended
      multiwalled carbon nanotube structures. When metal is deposited on a suspended
      multiwalled carbon nanotube structure, the nanotube acts as an evaporation mask,
      resulting in the formation of discontinuous electrodes. The metal deposits on the
      nanotubes are removed with lift-off. Using Al sacrificial layers, it was possible
      to fabricate self-aligned contact electrodes and control electrodes nanometers
      from the suspended carbon nanotubes with a single lithography step. It was also
      shown that the fabrication technique may also be used to form nano-gapped contact
      electrodes. The technique should prove useful for the fabrication of nano
      electromechanical systems.

PMID- 14598448
TI  - Modeling a submicrometer electrostatic motor.
AB  - Numerical models are developed for a recently proposed submicrometer device that
      uses the electric field energy of a biased parallel-plate semiconducting
      capacitor to propel a piston through the open capacitor gap. Through variation of
      design parameters or applied external bias, actuator forces on the order of
      hundreds of piconewtons are developed for device size scales ranging from 10(-7)
      m to 10(-4) m per side. A rotary configuration of the device is also presented.

PMID- 14598449
TI  - Raman spectroscopy and structure of crystalline gallium phosphide nanowires.
AB  - Gallium phosphide nanowires with a most probable diameter of approximately 20.0
      nm and more than 10 microns in length have been synthesized by pulsed laser
      vaporization of a heated GaP/5% Au target. The morphology and microstructure of
      GaP nanowires have been investigated by scanning electron microscopy and
      transmission electron microscopy. Twins have been observed along the crystalline
      nanowires, which have a growth direction of [111]. Raman scattering shows a 4 cm
      1 downshift of the longitudinal optical phonon peak in the nanowire with respect
      to the bulk; the transverse optical phonon frequency and line width are, however,
      the same as in the bulk. The quantum confinement model first proposed by Richter
      et al. cannot explain the observed behavior of the Raman modes.

PMID- 14598450
TI  - Synthesis of gold-silica composite nanowires through solid-liquid-solid phase
      growth.
AB  - Nanoscale wires of silicon oxide, and silicon oxide with embedded gold-silicide
      nanospheres, are synthesized by heating of a gold-coated silicon wafer at
      temperatures of 1000 degrees C or above, with the resulting wires having
      diameters ranging from 30 to 150 nm and lengths of approximately 1 mm. This
      simple fabrication process should make possible economical bulk production of
      nanowires. Studies indicate that the growth of these gold-silica composite
      nanowires occurs directly on the silicon wafer by a solid-liquid-solid mechanism.

PMID- 14598452
TI  - HIPAAnoia plagues outsourced IT vendors. Telemedicine's battle is with forces
      behind a firewall.

PMID- 14598451
TI  - Scanning probe microscopy with landmark referenced control for direct biological
      investigations.
AB  - We report the successful use of continuous wavelet transforms applied to atomic
      force microscope data sets for landmark recognition of biological features. The
      data sets were images of mixed red and white blood cells. Contrast enhancement
      followed by continuous wavelet transform of the data was used to successfully
      distinguish erythrocytes from neutrophil and monocyte leukocytes within the mixed
      cell images. All of the above are spherical objects between 6 and 8 microns in
      diameter, which demonstrates the ability to sort similar biological objects into
      distinct classes. The implications for development of on-line scanning probe
      recognition microscopy are discussed.

PMID- 14598454
TI  - Pick your own pocket. Today's CIOs can often find their successors within their
      own IT ranks.

PMID- 14598453
TI  - Think small. Are PPM vendors meeting the needs of small practices?

PMID- 14598455
TI  - The nature of a successful CIO. Thriving leaders have certain characteristics,
      and so do their organizations.

PMID- 14598456
TI  - CIOs don't just happen. It takes a professional development plan and some serious
      grooming to prepare your successor.

PMID- 14598457
TI  - A boost to service and quality. California addresses the ills of healthcare with
      selective technology investments.

PMID- 14598458
TI  - The continuity of care record. Organizations unite to create a portable,
      electronic record for use at transfer points in patients' care.

PMID- 14598459
TI  - Co-piloting to success. Clinical and financial partnerships let a physicians
      group concentrate on its strengths.

PMID- 14598461
TI  - Drivers of a network upgrade. Good planning ensures a strong organizational
      backbone with a minimum of pain.

PMID- 14598460
TI  - Clinical-information connectivity nationwide. Healthcare can use the model of
      success frontiered by banks.

PMID- 14598462
TI  - Building on the infrastructure. Total systems replacement isn't the only way to
      support new technologies.

PMID- 14598463
TI  - The final security rule. Compliance begins with risk analysis.

PMID- 14598465
TI  - Mobile documentation. Wireless PDAs boost job satisfaction for utilization review
      nurses.

PMID- 14598464
TI  - Organizing oncology. New software targets cancer therapy.

PMID- 14598466
TI  - Real-time fraud detection. Systems with predictive analytics can catch fraud and
      abuse before they happen.

PMID- 14598467
TI  - Orthopedic advances require revised provider strategies.

PMID- 14598468
TI  - Tenet Healthcare faces tough turnaround.

PMID- 14598469
TI  - Report shows quality of health care varies dramatically by state.

PMID- 14598470
TI  - Providers, public wake up to the value of sleep centers.

PMID- 14598471
TI  - Sleep medicine an evolving discipline.

PMID- 14598472
TI  - [The use of monoclonal antibodies in studying the causative agents of viral
      hemorrhagic fevers].
AB  - The most promising trends of using monoclonal antibodies (Mabs) in virology
      research of the viral hemorrhagic-fevers' agents are related with studying viral
      antigen structure and with developing diagnostic preparations for indicating and
      identifying infectious agents of the mentioned pathologies. The methodological
      specificity of obtaining the Mabs to viral hemorrhagic-fevers' agents as well as
      data on its practical use are discussed.

PMID- 14598473
TI  - [ West Nile fever among residents of the Astrakhan region in 2002].
AB  - Thirty-three persons infected with West Nile fever were detected in 2002 in the
      Astrakhan Region; the diagnosis was confirmed serologically and the maximal
      number of the infected was registered in August, same year. The indices of the
      specific humoral immunity varied from 3.3% to 27.1%. A monitoring determined the
      highest infection risk among the residents of the Volga middle delta.

PMID- 14598474
TI  - [Genetic variations of hepatitis C virus circulating in the Ural region].
AB  - A study of distributions of different genetic variations (subtypes) of hepatitis
      C virus (HCV), circulating in the territories of Yekaterinburg and Chelyabinsk
      among infected population categories of different social statuses and age, is
      reported in the paper. The predominance of 1b subtype was shown in the HCV
      infected patients at the hemodialysis center (HDC) and at the pediatric
      oncohematology center (OHC), 83.3% and 84.6% respectively. The summarized results
      of examinations of patients conducted at HCV-infection departments (97 persons)
      did not reveal any essential differences between the data, obtained for Moscow
      and Saint-Petersburg, concerning the distributions of HCV subtypes. However,
      according to an analysis made in cities of the Urals region, the prevalence of 1b
      subtype in Chelyabinsk was 2-fold higher than that of 3a subtype, whereas in
      Yekaterinburg there was an equal ratio (1:1) between the above subtypes. Besides,
      unequal distributions of HCV subtypes were registered in different age groups. 3a
      subtype was found to be predominant in patients aged 15 to 27, and prevalence of
      1b subtype persisted in persons aged below 15 and above 27. The conclusion is
      that the redistributed occurrence rates of separate HCV subtypes, with their
      spectrum in mentioned territories being preserved, is associated with a growing
      number of young drug-addicts who are more often get infected with 3a subtype.

PMID- 14598475
TI  - [The use of bromelain in obtaining the subviral particles of influenza A and B
      viruses].
AB  - Subviral particles of modern strains of influenza A viruses, i.e. A/New
      Caledonia/20/99 (H1N1), A/Moscow/10/99 (H3N2), reassortant X-31 (subtype H3N2)
      and B/Sichuan/379/99, were obtained by using two preparations of bromeline
      ("Sigma Co., Catalogues' Nos. B2252 and B5144). A selective ability of bromeline
      B5144 was detected to the proteolytic splitting of hemagglutinin of influenza A
      and B viruses. An influence of enzyme B5144 produced on influenza B viruses
      brought about an appearance of subviral particles. As for influenza A(H1N1)
      virus, the above enzyme did not have any impact on it under the similar
      experimental conditions. An incomplete effect was noted for the influenza A(H3N2)
      virus with particles (with intact external coatings) being found in the reaction
      mixture. Enzyme B2252 was found to be effective in respect to all viruses
      selected for testing, however, the highest effect was noted for influenza A(H1N1)
      and B viruses.

PMID- 14598476
TI  - [Structure and antiviral activity of adamantane-containing polymer preparation].
AB  - New water-soluble antiviral chemical agents, containing 10 to 30% of adamantane
      derivatives (amino-, aminopropyl-adamantane-, aminomethyl- and rimantadine),
      which were conjugated with polycarboxylic matrixes of the divinyl ether and
      maleic anhydride copolymers (DIVEMA), were developed. The polymeric drugs
      exhibited a low cytotoxicity (4 to 10 times less than rimantadine) and a wide
      spectrum of antiviral activity against influenza viruses, including both the
      remantadine-resistant strains of A/PR/8/34 (H1N1) and the B/Saint-Petersburg
      strain/71/77 as well as against herpes viruses of type 1, parainfluenza viruses
      of types 1 and 3 and RS-virus. A reduction of the viral infection titer in their
      reproduction in sensitive cells' cultures was more than 2.0 Ig ID50. Complete
      inhibition of viral-specific syntheses, registered by immune-enzyme assay (IEA)
      and by hemagglutination test was observed at low infection doses ranging from 1
      to 100 ID50. The efficiency of the antiviral effect depends on a drug's molecular
      weight and a structure of chemical bonds between the adamantane nucleus and the
      polymeric matrix.

PMID- 14598477
TI  - [The impact of compound of double-stranded RNA and hyaluronic acid on the
      parameters of non-specific resistance in mice].
AB  - The effect of yeast double-stranded RNA (dsRNA) and of hyaluronic acid (HA)
      compositions produced on the interferon synthesis, peritoneal phagocytic activity
      of macrophages and on the hematological parameters were studied in an experiment
      with white noninbred mice. HA was shown to enhance the dsRNA-induced interferon
      synthesis, to inhibit the leukopenic reaction and to produce no effect on the
      phagocytosis-stimulating activity. The data obtained are indicative of that HA is
      a promising preparation regarding its use within the interferon-inducing
      compositions based on dsRNA.

PMID- 14598478
TI  - [The antiviral activity of peptide immunomodulator "Gepon" in experimental
      infections caused by herpes simplex viruses types 1 and 2].
AB  - Experimental data are reported on the antiviral activity of peptide immune
      modulator "Gepon" in infections caused by herpes simplex virus (HSV), types 1 and
      2, in vitro and in vivo. The drug proved to be non-toxic and did not possess any
      viricidal action. Its antiviral effect was registered in experiments with a
      multiple-infection cells' culture. The maximal effect was a 100-fold reduction of
      the viral titer when it was used in a concentration of 6.25 mcg/I as a preventive
      measure 24 hours before triggering the infection. The mentioned drug's effect was
      reliably higher than its use within a treatment scheme (1 hour after the
      infection onset). "Gepon" possessed the reliable protecting qualities (36% of
      protection with a mean increase of the infected mouse life by 1.9 days) in
      experiments with intraperitoneally infected mice (10 LD50/mouse of HSV, type 2),
      when the drug was administered in doses of 0.1 and 1 mcg/mouse.

PMID- 14598479
TI  - [An experimental infection caused by the EP-2 strain of cowpox virus in mice of
      different ages].
AB  - The specificity of lethal infection was studied in noninbred white mice (age--15
      to 20 and 25 to 30 days) infected intraperitoneally with the EP-2 strain of
      cowpox virus (CPV) in doses 10(5), 10(6) and 10(7) PFU. The virus caused the
      lethal infection in the 15-20-day mice; while the 25-30-day mice remained healthy
      and survived. Virologic, immunologic-and-histochemical and electron-microscopy
      examinations of the 15-20-day mice revealed a replication of the EP-2 strain in
      tissues bordering on the virus introduction area; there was no generalization of
      infection. The virus replicated first in the mesothelium cells, and after that,
      in fibroblasts as well as in the endothelial, fatty, adventicial, cross-striated
      and muscle cells and in myosatellites.

PMID- 14598481
TI  - [Indication, genotyping and phylogenetic analysis of bovine diarrhea virus
      obtained in the territory of the Russian Federation ].
AB  - Bovine diarrhea virus (BDV) is widespread throughout the European part of the
      Russian Federation. The BDV genome is detected in around 40% of animals (aged up
      to 18 months) with lesions in the gastrointestinal tract and respiratory system.
      It can be found in all intestinal sections, including its contents and feces, in
      lymphoid and respiratory organs as well as in nasal washings and discharges and
      in vaginal tunic discharges of cows. Primary structure analysis of 5'
      untransalted region of the genome of the detected isolates revealed that all of
      them belonged to genotype 1. Phylogenetic analysis confirmed that a part of
      isolates belonged to subgenotype 1a, while most isolates make up a separate
      group. No geographic differences were reported in the circulation of the BDV
      genetic variants within Russia's territory.

PMID- 14598480
TI  - [A quantitative evaluation of blood-lymphocyte subpopulation in herpetic ocular
      disease].
AB  - Data on changing contents of blood-lymphocytes' subpopulations in patients with
      ophthalmoherpes are reported. A higher number of blood cells expressing the
      surface activation antigens of HLA-DR+, CD71+ and CD95+, a lower number of T
      helpers and a reduced value of the immune-regulating index were found to be
      typical of such changes. A more significant increase in the quantity of CD95+
      lymphocytes, as observed in cases of severe ophthalmoherpes versus its moderate
      clinical course, could be a prognostication criterion. The essential shifts
      occurring in the T-cells' population denote the status of tension in the immune
      response provoked by an intensified reproduction of herpes simplex virus (HSV);
      at the same time, they are indicative of a certain deficit in the immune
      protection mechanisms.

PMID- 14598482
TI  - [Detection and differentiation of the bovine parainfluenza-3 virus strains
      studied by amplification and sequencing of the HN gene].
AB  - A possibility of using the amplification of gene HN fragment in combination with
      nucleotide cDNA sequencing for the purpose of identification and strain
      differentiation of bovine parainfluenza-3 virus was demonstrated. A comparative
      analysis of the primary structure in the studied HN gene fragment revealed 2
      genetic groups among the investigated virus' strains and isolates. Group 1 is
      made up of Northern American viral strains and of Russian isolates, whose primary
      structure has a high level of homology to the primary SF-4/32 strain structure;
      group 2 comprises the virus' Russian isolates with a high level of homology to
      the mentioned strains to Japanese strains' sequences. The biggest differences
      between the studied strains and the viral isolates amounted to around 8%, when
      the nucleotide sequences were compared, and to around 4%, when the corresponding
      amino-acid sequences were compared.

PMID- 14598483
TI  - [Experience in penetrating keratoplasty in children: graft survival, functional
      results and risk factors].
AB  - Penetrating keratoplasty in children is related with a labor-consuming process of
      follow-up and care as well as with a high risk of graft rejection and a moderate
      vision improvement. Nonetheless, keratoplasty has been and still remains a
      surgery of choice due to a lack of an alternative procedure; its technique and
      results have been gradually promoted in practice. The authors analyzed 112
      keratoplasties in childhood-age corneal opacifications of different types. The
      graft survival amounted to 71%, 61% and to around 55% after 1, 2 and 5
      postoperative years, respectively. Neovascularization, glaucoma, repeated
      keratoplasty, an original vitreous pathology, an expanded surgical scope
      (reconstructions) etc. were attributed to risk factors. The visual acuity
      improved by more than 0.02 in 54% of cases; it remained unchanged or worsened in
      22% of cases and it could not be assessed in 24% of cases. The best results were
      achieved in a group of patients with acquired corneal opacifications of the
      nontraumatic nature; the worst results were observed in congenital anomalies of
      the anterior eye segment. Finally, the success of penetrating keratoplasty in
      children was ensured through a careful selection of patients, an accurate
      surgical technique and through a fast treatment of postoperative complications.

PMID- 14598484
TI  - [Ultrasonography of intraocular pathology in a pediatric oncology clinic].
AB  - Forty-seven children with the intraocular acoustic effect of "plus-tissue", which
      was preconditioned by retinoblastoma, Coats' disease, retinopathy of the scarring
      stage in premature newborns and differentetiology fibroses of the vitreous body,
      underwent ultrasound examinations, including color Doppler mapping and pulse
      Doppler-graphy, for the purpose of promoting the differentiated diagnostics.
      Determinative ultrasonographic criteria were specified for each of the mentioned
      pathology states; a special significance of Doppler tools is pointed out in
      detecting a nature of the neovascular network, in identifying a.hyaloidea present
      in premature newborns and also present in retinal detachment with profound
      vitreous changes.

PMID- 14598485
TI  - [The modern methods of monitoring the optic nerve disk and specificity of
      glaucomatous optic neuropathy in normal-pressure glaucoma].
AB  - The purpose of the case study was to determine an optimal method for monitoring
      the condition of the optic nerve disk (OND) and for precising the OND
      peculiarities in patients with normal pressure glaucoma (NPG). A comparison of
      the OND calculated parameters obtained for 16 patients (31 eyes), both by the
      "Rodenstock" scanning laser ophthalmoscope (SLO) and by HRT-II, revealed that the
      OND parameters calculation preformed by HRT-II was more informative, diversified
      and automated, which essentially cuts the procedure time. We examined, by HRT-II,
      a group of 31 patients (61 eyes), comprising patients with high pressure glaucoma
      (HPG), with suspected NPG and with moderate-pressure glaucoma (MPG) and a group
      of controls with moderate arterial hypertension. A comparison of OND areas'
      distributions of three groups (NPG group, MPG group and HPG group) showed that
      the majority of disks had an area ranging from 2.0 to 2.6 mm2 in the NPG, the
      same index ranged from 1.8 to 2.2 mm2 in the MPG group, and in the HPG group the
      disks were evenly distributed by area virtually in all ranks. The OND area was on
      the average less (2.13 mm2) in an impaired autoregulation versus the group
      without any symptoms of peripheral vasospasm (2.49 mm2). According to our
      findings, a higher OND size contributes to aggravating glaucoma at a lower
      intraocular pressure (IOP). It is noteworthy, that more pronounced changes are
      observed on the side with a bigger OND area in absence of any other risk factors,
      e.g. neuro-ophthalmic pathology or stenosis of the main cerebral arteries.

PMID- 14598486
TI  - [A differentiated approach to the treatment of normal-pressure glaucoma].
AB  - Seventy patients with normal pressure glaucoma (NPG) were treated on the
      differential basis with respect to a pathogenetic disease type. The suggested
      complex therapy of the ischemic variation improves both the microcirculation in
      the optic nerve disk (OND) by administering different-effect drugs in long
      courses and the systemic hemodynamics (practitioners of needed skills are
      involved). The use of local antihypertensive drug to reduce the intraocular
      pressure to an individual tolerable value is important in the treatment of
      patients with tension-ischemic glaucoma. The process stabilized in 75.8 +/- 3.9%
      of patients in the main group and in 47 +/- 8.5% of patients in the control group
      (p < 0.05) after a follow-up of up to 2.5 years.

PMID- 14598487
TI  - [Clinical experience in using a metallic suture in eye microsurgery].
AB  - The use of a metallic suture in eye microsurgery is described in the paper. The
      metallic suture made from a 0.05-0.05 mm vanadic stainless steel wire
      (corresponding to 8:0) was applied in 1202 cataract extractions, penetrating
      injuries, antiglaucomatous surgeries and in removal of pterygium at the medical
      and-sanitary facility of steel works in the town of Bokaro (India). The
      observation period ranged, on the average, from 3 months to 3 years. There were
      no complications during the procedure of applying the suture. However, it caused
      a minor response in the ocular tissues during the early postoperative period.
      Small bullae were observed in the corneal surface near the suture in 7 cases
      (0.58%), which disappeared spontaneously in 3-4 days. Irritations inflicted by
      the suture ends were registered in 2.58% of cases (31 patients). The mean
      postoperative astigmatism was, 3 months after surgery, 1.65 diopters. The sutures
      were removed in 132 cases (10.98%), including in 16 patients with irritation, and
      in 116 patients for the purpose of correcting a high astigmatism. The share of
      patients with a visual acuity of 0.5 and higher was, in one week, 43.59% and went
      up, one month later, to 78.20%. The suture was well tolerated by patients, it was
      quickly covered by the corneal epithelium, there was no rejection and it can be
      easily manufactured. The suture is sterilized by routine techniques without need
      for any extra treatment before use; it is a reactive, biologically inactive,
      efficient, convenient and causes minimal operative and postoperative
      complications.

PMID- 14598488
TI  - [Photo-ablation of a corneal epithelium flap in complications after laser
      keratomileusis].
AB  - Three hundred and fifty-four LASIK surgeries made in myopia were analyzed. The
      share of epithelium-related complications made up 3.1%. Persistent irregular
      astigmatism and impaired visual acuity with correction shaped up in 5 cases. All
      patients underwent laser photoablation of the epithelium in the phototherapeutic
      keratectomy (PTK) regimen by using an original technique. The "Keracor 217 C"
      laser (2 mm spot, 120 mlJ./cm2 energy and 25 Hz frequency) was applied. The
      treatment resulted in a reliably improved visual acuity and normalized anterior
      corneal surface.

PMID- 14598489
TI  - [Optimization of energy parameters of ultrasound and laser cataract surgery with
      a preliminary transcorneal endocapsular YAG-laser impact exerted on the cataract
      lens nuclei].
AB  - The values of the main energy and time parameters of ultrasound and laser
      fragmentation of different-hardness cataract-lens nuclei were analyzed in
      patients of various age groups after a preliminary transcorneal endocapsular YAG
      laser treatment of the lens. The results show, in all cases, lower key energy and
      time characteristics, which primarily concerns a total energy index of the
      ultrasound and laser effect of no less than 20% versus the ordinarily used
      parameters.

PMID- 14598490
TI  - [New clinical forms and diagnosis of ophthalmic chlamydiosis].
AB  - The paper deals with new clinical forms of ophthalmoclamidiosis involving lesions
      to the choroids, retina, optic nerve and cornea. Uveitis and scleritis were found
      in 73.5% and 26.5%, respectively. Iridocyclitis and paneveitis prevailed in cases
      of uveitis. Forty-two patients, aged 3 to 53, were followed up. Bilateral ocular
      lesions were registered in 67% of them. The progression, clinical course and
      outcomes of the disease were investigated by using the up-to-date laboratory-and
      immunologic methods. Direct immunofluorescence and polymerase chain reaction,
      when used alongside with serological examinations, were found to be most
      informative. A combination of ophthalmoclamidiosis with urogenital pathologies
      was registered in 76% of patients.

PMID- 14598491
TI  - [Pulse therapy in the treatment of optic neuritis in multiple sclerosis].
AB  - Corticosteroids are the preparations in the treatment of optic neuritis at
      multiple sclerosis. The doses and methods of introduction of corticosteroids are
      chosen individually for the adults and children. A maximum effect is registered
      in a majority of cases of optic neuritis, when methylprednisolone is prescribed
      with the pulse-dose introduction, as compared to parabulbar injections or
      administration of corticosteroids per os. The recovery of vision at relapsing
      optic neuritis sets on faster and is of a more prolonged nature as compared to
      other variants of the introduction of corticosteroids. Therefore, the
      prescription of methylprednisolone as pulse-doses is more effective in both
      adults and children.

PMID- 14598492
TI  - [Changes in the total lacrimal output in patients with various-stage diabetic
      retinopathy in insulin-dependent diabetes mellitus of different severity].
AB  - A total of 99 patients (198 eyes) with insulin-dependent diabetes mellitus (IDDM)
      without diabetic retinopathy (DR) and DR of various stages were observed.
      Disorders in the total lacrimal output (TLO) were detected in a majority of the
      observed patients; it is noteworthy, that the indices of Schirmer's test (ST)
      ranged widely and were of a diversified nature--from hypersecretion to a virtual
      lack of lacrimal fluid. A correlation was established between a defect of
      lacrimal output and a nature of the clinical course of the principle disease-
      IDDM (duration, severity, presence of diabetic nephropathy and violations of
      lipid metabolism) and also a patient's age. A retrospective analysis showed that
      the changes in TLO precede the onset and aggravation of DR. Lacrimal
      hypersecretion is associated, as a rule, with a lack of DR or with a
      stabilization of initial changes in the retina. The deficit and/or asymmetry of
      TLO as well as reduced values of TLO, while studied dynamically and irrespective
      of the initial TS values, can serve as risk criteria in the DR aggravation;
      besides, they can be used in practice for prognosticating the DR clinical course
      in IDDM patients.

PMID- 14598493
TI  - [Experimental study of the effectiveness of a silicone protector designed for the
      vitreous body and retina in phacoemulsification].
AB  - A phacoemulsification technique is suggested that involves the use of a silicone
      protector. It was proven experimentally that a temporary implantation of a
      silicone plate, i.e. protector, into the retronuclear space, while performing the
      lens nuclear phacoemulsification, is an effective means of protecting the retina
      and vitreous body from a negative ultrasound impact.

PMID- 14598494
TI  - [A system of digital analysis for the diagnosis of vascular pathologies of the
      fundus oculi].
AB  - A diagnostic tools' set was worked out for the digital analysis of eye-fundus
      images; it comprises a retinophot and a digital camera adapted to it as well as a
      computer system and a special soft. A new mathematical model of a fragment of the
      ocular main microcirculation vessel and the below related global diagnostic
      parameters of the vascular system were elaborated: mean diameter, deviation from
      linearity, image acutance, fluctuations' amplitude for thickness and route, and
      sinuosity of thickness and route. The system of eye-fundus image processing
      provides for precising a nature of changes in vascular thickness along the route
      and for assessing the local diameter by using the vascular profile; it can also
      be used for determining the angle of vessels' branching. A set of expert
      diagnostic etalons was set up for vascular pathologies of the eye fundus and an
      appropriate database was created. The advantages of the designed system are: the
      possibility to use it comprehensively in clinical practice, less time needed to
      make and to analyze the eye-fundus images, a higher accuracy in determining the
      local vascular diameter, the possibility to perform simultaneously an analysis of
      diagnostic signs of retinal vessels on the basis of using a radically new
      approach towards assessing the vascular system ("tracing-type isolation of
      segments"), a higher diagnostic efficiency, the possibility to perform the
      differential diagnosis and the capability of preserving data without any
      limitations by volume and store duration time.

PMID- 14598495
TI  - [A functional model of a state district ophthalmologic clinic under the budget
      deficit conditions].

PMID- 14598496
TI  - [Ophthalmologic consequences of diabetes mellitus: social-hygienic and clinical
      aspects].

PMID- 14598497
TI  - [Surgical tactics in eye injuries and their sequelae according to specialized
      unit data].

PMID- 14598498
TI  - [Use of prenacide magnetophoresis in complex treatment of some ocular diseases].

PMID- 14598499
TI  - [Use of 2% anilocaine solution for injections in ophthalmology].

PMID- 14598500
TI  - [Orbital complications in purulent-inflammatory diseases of the paranasal
      sinuses. Clinical and anatomic parallels].

PMID- 14598501
TI  - [Visual impairment in empty sella syndrome].

PMID- 14598502
TI  - [Moscow School of Ophthalmology: Professor A. A. Kriukov].

PMID- 14598503
TI  - [Role of DNA diagnosis in modern oncology].
AB  - DNA-diagnosis became to be a mandatory element of the modern oncological care.
      The molecular-genetic approaches aimed at identifying the high-risk categories in
      oncology are mostly-renowned. They comprise the diagnosis of the so-called
      familial cancerous syndromes, the identification of unfavorable normal genome
      variations (gene polymorphisms) and the detection of a number of oncoviral
      infections. Laboratory procedures facilitating the individualization of treatment
      schemes and the monitoring of oncology patients have been widely introduced into
      clinical practice. The turn between the 20th and 21st centuries was marked by the
      emergence of principally new DNA-analysis methods designed for a comprehensive
      and integral genome evaluation. The application of such radically novel
      techniques in the molecular diagnostics essentially promoted the detection and
      treatment of neoplasms.

PMID- 14598504
TI  - [Scientific and practical aspects of prenatal diagnosis].
AB  - Prenatal diagnostics (PD) is a relatively new branch of medical genetics
      enjoining presently a rapid practical and scientific progress. The key practical
      issues related with detecting the pregnant women at high risk of fetal congenital
      and inherited pathologies have already been solved, and a variety of fetal
      examinations by non-invasive (ultrasound) and invasive (cytogenetics,
      biochemistry and molecular tests) methods have been elaborated. Their practical
      application are totally dependant on the managerial and financial input in the
      discussed field of medicine. Further advancement in PD are tensely associated
      with early pregnancy stages (trimester 1), with the molecular diagnostic tools in
      the diagnosis of chromosomal diseases and with a comprehensive use of Pregnancy
      Genetic Form worked out and used already at our institute. DP opens up the
      promising opportunities for analyzing the human genome activity at the initial
      development stages, which comprises the revision of previously-obtained data on
      the cytogenetics of human embryo evolution, human chromosomes' functioning and of
      temporary embryonic organs as observed during the mentioned stages; it also
      comprises an analysis and application of umbilical and embryonic cells (embryonic
      cell therapy) and elaboration of scientific fundamentals for embryonic gene
      therapy. PD should not be referred to only as a set of diagnostic methods for it
      is also a good starting-ground for research of human embryo-genesis.

PMID- 14598506
TI  - [Innovative technologies in the complex treatment of patients with rheumatoid
      arthritis].
AB  - The treatment of rheumatoid arthritis (RA) remains a difficult task since the
      current therapy does not always result in the disease remission. The search for
      and development of new methods and principles for the complex therapy of RA have
      been underway. 144 RA patients aged 22 to 65, disease duration--72.4 +/- 7.3
      months, have been investigated. A majority of them (62.3%) had stage 2 RA, and
      77.4% had RA stages 2-3. The patients who were taking methotrixate for 5 years
      were found to respond better and longer to the traditional-therapy drugs versus
      drugs of other basic groups. An intensification of treatment (by
      methilprednizolone combined with cyclophosphamide) in a group of stage 1 RA
      patients) improperly responding to the therapy (resulted in a disease remission
      for as long as 2.5 months. An intensification of therapy in stage 2 RA (by
      cyclophosphamide, vincristin and prednizolone) entailed a 13.2-month remission in
      23 patients. A big number of contraindications restrict the use of such intense
      therapy which should be replaced, in such cases, by anticytokine drugs. Remission
      and improvements were ensured after remicade in 4 and 2 of 7 RA patients
      respectively. DMARS provided a significantly lower RA intensity that lasted,
      however, only for 2 weeks, which necessitates further research related with
      higher drug's doses and with extending its effect. Stem-cells transplantations
      were used in RA, after which remission and improvements were observed in 80% of
      patients.

PMID- 14598505
TI  - [Current views on migraine and anti-migraine preparations].
AB  - On the basis of comprehensive experimental and clinical research the authors
      defined a variety of migraine-related mechanisms and schemes of migraine
      correction by drugs, which should be both of the vascular- and general-actions to
      ensure an effective medication.

PMID- 14598507
TI  - [The scientific and clinical value of molecular genetic changes in the
      intercellular gap junctions observed in colon cancer].
AB  - Colon cancer is one of the most widespread pathologies with high mortality due to
      recurrence and metastasis. The molecular methods of diagnosis, prognostication
      and biotherapy in colorectal cancer enjoyed a rapid progress during the recent
      decades. The hypothesis on the key role of impaired intercellular gap junctions
      in the onset and progression of malignant tumors is a promising trend in
      carcinogenesis research. We have recently discovered a variety of tumor-specific
      mutations of connexin 43 gene in advanced colorectal cancer (Oncogene. -2002.
      Vol.21, No.32-pp.4992-4996), which confirms the above hypothesis in malignant
      tumor progression. We believe that further studies of connexins' mutation changes
      in tumor growth is a promising trend in research of its etiology and pathogenesis
      and in designing new methods of diagnostics and treatment of colonic and other
      gastrointestinal cancers.

PMID- 14598508
TI  - [New achievements in the diagnosis and treatment of disseminated urogenital
      chlamydiosis].

PMID- 14598510
TI  - [Use of modern technologies in the diagnosis and combined treatment of brain stem
      tumors].
AB  - The latest technologies, introduced into neurosurgery during the last 2 decades
      of the 20th century, ensured progress in the diagnostics and treatment of
      brainstem tumors--pathologies that remain until now a most complicated problem in
      neurooncology. The modern diagnostic tools comprising profound dynamic
      neurological and neurophysiological examinations (AVP, EEG) visualization
      techniques (CT, MRT with contrasting, MRT, spectroscopy, PET) provide for
      detecting not only the initial signs of stem tumors and their sizes but also
      their topographic interaction with the stem structures; it, in its turn, opens up
      a possibility to choose between the combined surgical treatment and the
      radiotherapy or chemotherapy alone. The clinical course, diagnosis and combined
      treatment of 333 children and adults with tumors bordering on the brainstem are
      analyzed within the case study.

PMID- 14598511
TI  - [New blood substitutes of polyfunctional action].
AB  - The paper deals with two categories of new oxygen-carrying blood substitute
      solutions (OCBSS), based on a modified hemoglobin (MG) and perfluor-organic
      carbon emulsion (PCE), and with crystalloid and colloid blood substitutes of the
      antihypoxic action containing the Crebs' substrate (sodium fumarat). Described
      are the results of clinical use of Russian OCBSS based on MG (Gelenpol) and on
      PCE (Perftoran) in 151 patients with hemorrhagic shock and intraoperative blood
      loss. Both drugs are allowed for medical application in Russia. Gelenpol was
      administered at 1 to 6 units, perftoran--at 10-15 ml/kg. An improved oxygen
      status as well as normalization of hemodynamics, microcirculation, rheology, and
      of blood acid-base balance (ABB) were registered. Gelenpol had a hematosis
      stimulating action. The combined use of both drugs or one of them alone in
      surgery is under discussion. The OCBSS efficiency can be enhanced when they are
      used jointly with the first Russian infusion antihypoxants containing sodium
      furmarat, i.e. Mufasol and Polyoxyfumarin. Both of them were shown to normalize
      the oxidation in tissues, to recover the mitochondrial metabolism in the liver
      and myocardium and to improve the blood ABB when used in hypovolemic and hypoxic
      conditions of different etiologies, in substituting for intraoperative blood
      losses (gastrointestinal hemorrhages), in polytrauma and destructive
      cholecystitis as well as in preoperative preparations of patients with diffuse
      peritonitis. The OCBSS preparations and antihypoxants are undoubtedly drugs of
      choice in emergency infusion-transfusion therapy and in cases of multiple victims
      from accidents.

PMID- 14598509
TI  - [The modern organ- and function-sparing surgical treatment in oncology].
AB  - The results of organ-sparing treatment of patients with cancers of the breast,
      uterine cervix, endometrium and ovary are described in the paper. A prospective
      randomized clinical study launched in 1995 at Petrov's Research Institute of
      Oncology comprised cases of above 700 patients with breast cancer, around 300
      women with cancer in situ and with microinvasive cancer of the uterine cervix and
      83 patients with initial endometrial cancer. The results of the above treatment
      (segment resection + axillar dissection + radiotherapy) were shown to be similar
      to those obtained after Petey-Dyson mastectomy (5-year survival of 86.7% versus
      88.8%, p = 0.81). The risk of local recurrence was increasing in patients with
      the tumors' diameter of more than 1 cm who were not treated by radiotherapy. The
      total regression of tumors was registered in 70% of patients with initial
      endometrial cancer after hormone therapy by progestagens and antiestrogens; 20%
      of them maintained the reproductive function.

PMID- 14598512
TI  - [Modern technologies of diagnosis and combined surgical treatment in liver
      tumors].
AB  - Modern technologies used at St. Petersburg Central Research Institute of
      Roentgenology and Radiotherapy of Russia's Ministry of Health in the diagnosis
      and treatment of malignant and benign liver cancers are surveyed in the paper.
      Apart from routine examinations, like ultrasound scanning, computer tomography,
      MRT, angiography, the below new technologies were widely used: multi-stratum
      spiral computer tomography, special MRT techniques and positron-emission
      tomography. The new methods enabled us to diagnose the tumor and its extension,
      to choose an optimal intervention technique, to make an objective assessment of
      the results and to correct the treatment strategy. Preoperative embolization of
      the portal-vein branches in the damaged hepatic lobe and postoperative adjuvant
      local chemotherapy of the hepatic artery and portal vein belong to the new
      combined surgical treatment scheme. The method of combined arterial-portal
      chemoembolization, used in unresectable malignant hepatic pathologies, extends
      the survival of patients by 3-5 times. Ferromagnetic embolization presupposes the
      administration of ferromagnetic, through the arterial bed or direct puncture,
      into the tumor with a subsequent SHF-current treatment which brings about a
      selective tumor hyperthermia without heating the normal hepatic parenchyma.
      Arterial embolization combined with local injection sclerotherapy in hemangiomas
      of the liver provides for a complete regeneration of benign tumors and can be
      regarded as a low-trauma alternative to liver resection. The use of new methods
      of diagnosis and treatment expands the possibilities of surgical care for
      patients with hepatic neoplasms and essentially improves the treatment results.

PMID- 14598513
TI  - [Pharmacotherapy in heroin addiction: pharmacological approaches to remission
      stabilization and recurrence prevention].
AB  - After withdrawal arrest in many heroin addicts, they displayed the syndrome of
      anhedonia including affective disorders (depression, dysphoria, anxiety),
      dyssomnia and a pathologic craving for opiates. Anhedonia is often the cause for
      recurrence in heroine addiction, therefore, an appropriate treatment is an
      important aspect in recurrence prevention and remission stabilization. Since
      depression and drive for heroin are the key symptoms in anhedonia, we undertook
      the efficiency study of therapy (in anhedonia) by antidepressants belonging to
      the selective serotonin reuptake inhibitors (SSRI) and NMDA receptor antagonists,
      citalopram and memantine, respectively, which have a clinical antidepressant
      action and an experimental anti-addictive action. Both drugs were found to arrest
      effectively virtually all signs of anhedonia, however, their action on remission
      stabilization was rather moderate. It looked to be more promising to use, in
      remission stabilization, the uttermost antagonist of opiate receptors
      (naltrexone) blocking reliably all heroine effects. A double blind placebo
      controlled study, undertaken by us, convincingly showed a significantly smaller
      number of relapses with naltrexone in heroin addicts. At the same time, the drug
      had no valuable effect on the anhedonia symptoms, which worsened the compliance
      entailing a poorer therapy efficiency. Finally, a combination of naltrexone
      (blocking the heroin action and reducing the recurrence rate) with SSRI
      antidepressants (effectively arresting the anhedonia symptoms and improving the
      compliance with naltrexone medication and remission quality) is a most promising
      approach to remission stabilization and recurrence prevention.

PMID- 14598514
TI  - [Organization of tuberculosis-controlling work and its efficiency in the
      penitentiaries of the Ivanovo Region].
AB  - The incidence rate of tuberculosis is high in the penitentiaries of the Ivanovo
      Region and in 2000 it was 32 times greater than that in the Region (3122 versus
      96.7 per 100,000). Fluorography remains to be the main method of detection of
      pulmonary tuberculosis. It is performed on day 3 of admission of jail, then every
      6 months. Fluorography allows one to identify 85-90% of the patients with
      pulmonary tuberculosis. In the fluorgraphic interval, the sputum from patients
      with symptoms of suspected tuberculosis is tested by the Ziehl-Neelsen procedure,
      which makes it possible to detect more than 15% of the tuberculosis patients who
      isolate bacteria. The patients are treated with the routine regimens including 4
      first-line drugs. In 1997-2000, the rates of bacterial isolation session and
      decay cavity closure were in the range of 82.1-93 and 66.7-87.5%, respectively.
      Integration with civil tuberculosis service, the social security administration
      of the region, and the regional branch of the red-cross society has proved to be
      highly effective. The proportion of patients with tuberculosis who continued
      their treatment in tuberculosis facilities after release increased from 51.1% in
      2000 to 80% in 2001.

PMID- 14598515
TI  - [Incidence of tuberculosis among workers engaged in the penitentiary system in
      the Republic of Udmurtia].

PMID- 14598516
TI  - [Causes and factors of development of drug resistance in pulmonary tuberculosis].
AB  - To prevent secondary multidrug resistance and polyresistance of Mycobacterium
      tuberculosis (MBT), it is necessary to strictly observe the tested chemotherapy
      regimens during intensive care by using at least four essential antituberculous
      drugs (ATD) mainly in combination. The rehabilitative phase should be monitored
      at outpatient units of a day hospital. To prevent cross MBT infection with drug
      resistance to essential ATD and to efficiently use expensive reserve drugs, it is
      necessary to set up specialized inpatient units (wards) for treatment and rooms
      for outpatient receipt of patients who isolate drug-resistant MBT strains.

PMID- 14598517
TI  - [X-ray characteristics of disseminated pulmonary tuberculosis].
AB  - The X-ray pattern of disseminated pulmonary tuberculosis is considered in terms
      of examination findings in 98 patients. Under the present-day conditions, the X
      ray pattern of disseminated tuberculosis is more commonly characterized by a
      combination of focal shadows of varying diameters with a prevalence of foci of
      this or that size. Symmetrical areas of infiltration (14.3%) and relatively
      symmetrical systems of decay cavities (6%) were a major abnormal shadow. A total
      of 76% had a destructive process. There was a predominance of generalized
      processes with medium and large cavities.

PMID- 14598518
TI  - [Use of isofon in combined treatment of patients with acutely progressive forms
      of tuberculosis].
AB  - Isofon given in a dose of 800 mg daily for 1.5-2 months contributed to clinical
      and X-ray involution of a process in 16 of the 19 patients with acutely
      progressive destructive forms of tuberculosis. The drug proved to be effective in
      patients who isolated drug-resistant Mycobacteria tuberculosis, including those
      to a combination of isoniazide and rifampicin. When used in patients with
      significant immunodeficiency, isofon provided an immunomodulating effect. It
      caused relatively a great deal of adverse reactions as fever in 11 patients,
      weakness, dizziness in 5, and cardiac arrhythmia in 1. The findings show it
      necessary to perform further clinical trials of the drug.

PMID- 14598519
TI  - [Significance of tuberculosis of the large bronchi in the diagnosis and treatment
      of restrictive forms of pulmonary tuberculosis].
AB  - A total of 1223 new cases of restrictive forms of pulmonary tuberculosis were
      examined. Of them 652 and 598 patients were followed up in the period of the good
      (1980-1984) and poor (1997-2001) tuberculosis epidemiological situation,
      respectively. A comparative analysis has indicated that there has been recently a
      rise in the incidence of tuberculosis of main bronchi from 10.5 to 18.0%, which
      most commonly complicates intrathoracic lymph nodal or infiltrative pulmonary
      tuberculosis. A more severe clinical course and a more frequent bacterial
      isolation have been ascertained mainly in infiltrative, ulcerative, and fistular
      forms of bronchial tuberculosis irrespective of the form of pulmonary
      tuberculosis. The comprehensive examination of patients with restrictive
      pulmonary tuberculosis is certain to include bronchial fibroscopy that may
      determine the form and phase of bronchial tuberculosis, the rate of a process in
      the lung, make and differentiate its diagnosis, use systematic and topical
      therapy (with hydrocortisone aerosols, GINK, streptomycin), and cure bronchial
      tuberculosis within 2-3 months.

PMID- 14598520
TI  - [Clinical symptoms of pulmonary tuberculosis in patients aged over 60 years with
      different intensive chemotherapy tolerance].

PMID- 14598521
TI  - [Some clinical and immunological aspects of female pulmonary tuberculosis].
AB  - Expression of activation markers, such as CD25, HLA-DR), Fas-AG, CD16), on the
      lymphocytes was studied in female patients with tuberculosis (n = 40) and healthy
      donors. The level of antituberculous antibodies was measured in parallel in the
      sera of these patients. The above parameters were examined in relation to the
      nature of the microflora detected in these patients. Nonspecific co-infection in
      patients with active tuberculosis is an additional factor of activation of the
      immune system and simultaneously a factor that enhances the involvement of cells
      in apoptosis.

PMID- 14598522
TI  - [Pneumonia in patients from a tuberculosis dispensary].
AB  - In their everyday practice phthisiologists have to make a differential diagnosis
      and to treat patients with pneumonia who account for 2.7% of the patients treated
      at tuberculosis hospital. The main reason of diagnostic errors in patients with
      pneumonia in general hospitals is that the compulsory diagnostic minimum is not
      observed and the patients' sputum is not tested for acid-resistant Mycobacteria.
      The paper analyzes the results of treatment in 20 patients with pneumonia in the
      contagious isolation wards of the tuberculosis hospital, who were in-effectively
      treated in the outpatient setting. Multimodality treatment with broad-spectrum
      antibiotics, including rifampicin and streptomycin, aerosols, and physiotherapy
      may completely resolve infiltration and eliminate the clinical manifestations of
      the disease in 19 patients.

PMID- 14598523
TI  - [Accelerated determination of blood bacteriostatic activity in patients with
      tuberculosis by using the semiliquid culture medium].
AB  - Blood bacteriostatic activity (BBA) was studied in 87 patients with respiratory
      tuberculosis. Clinical Mycobacterium tuberculosis (MBT) strains and different
      culture media, such as solid (Lowenstein-Jensen and Middlebrook), liquid
      (modified Soton) and semiliquid (SM developed for accelerated determination of
      drug resistance in MBT) media were used. With isoniazid-resistance of MBT, the
      use of solid media yielded underestimated BBA. The SM medium based on the Soton
      medium added by 0.35% of culture agar and 25% equine serum was optimal, which
      provided evidence for BBA on day 7 (visual recording of MBT growth). Examination
      of BBA by means of SM revealed a clear inverse correlation between the degree of
      BBA and the bacteriological parameters of sputum study. The small numbers of
      sputum MBT cultures (a high correlation, r = -0.88; p = 0.01) and short bacterial
      isolation (average correlation, r = -0.65; p = 0.01) corresponded to the high
      values of BBA.

PMID- 14598524
TI  - [The specific features of a pathogen in acutely progressive pulmonary
      tuberculosis].
AB  - Examination of 318 patients with different forms of acutely progressive pulmonary
      tuberculosis (APPT) revealed massive bacterial isolation in 181 patients of them.
      In one fourth of the patients, Mycobacterium tuberculosis (MBT) colonies grew
      during a month; the mean growth duration was 38.3 +/- 12.7 days, which was
      indicative of the viability of Mycobacteria and of their high virulence if they
      were isolated in large amounts. A hundred and thirty-three patients were found to
      be drug-resistant, which is one of the characteristics of present-day APPT. Such
      patients more frequently developed multidrug resistance. Sixty-three patients
      were ascertained to have secondary drug resistance, of them 41 patients were
      found to have drug resistance that progressed during APPT therapy.

PMID- 14598525
TI  - [Pregnancy and tuberculosis--state-of-the-art].

PMID- 14598526
TI  - [Brief history of Robert Koch's research works on tuberculosis].

PMID- 14598527
TI  - [Ecosystem evolution: main stages and potential mechanisms].
AB  - Major differences between the Western and "Russian" (Zavarzin, 1995) paradigms in
      ecology and evolutionary biology are described. The "Russian" paradigm suggests
      that there exist two, rather than one, quite independent lineages--species
      evolution and ecosystem evolution. This is based on the idea that life may exist
      just as a nutrient cycle. The main terms and concepts of the "Russian" paradigm
      are defined more exactly. An attempt is made to develop this paradigm so that it
      would be possible to describe not only phenomenology, but also mechanisms of
      ecosystem evolution. To simplify evolutionary phenomena logically, it is
      suggested to use the concept of conditionally complete causal explanation
      (Lekevicius, 1984; 1985), i.e. deduce evolutionary mechanisms from major
      principles of functioning. This methodology is adapted to model the main stages
      of the evolution of nutrient cycles (3.8-2.0 bln. y.a.) and the appearance and
      evolution of biophagy (1.7-0 bln. y.a.). Based on a multitude of examples, it is
      shown that these are functional constraints that are the forces directing
      evolution; those constraints emerge during the interaction of organisms and while
      the latter interact with the abiotic environment. Since the structure of an
      ecosystem is non-rigid, each species is able to accumulate features useful to
      both an ecosystem and itself. Those are individuals that die and reproduce,
      whereas all structures, from macromolecules to ecosystems, evolve.

PMID- 14598528
TI  - [Annual cyclic changes and self-organization processes in the marine sea-bottom
      organisms].
AB  - The dynamics of marine microbenthos species structure shows clear annual cycle.
      From late winter till early autumn community changes towards increasing
      complexity and orderliness. The sharp increase in available energy (light and
      heat) in the beginning of the winter acts as trigger of these processes. The
      further development of the community is connected with system fluctuations
      arising as a result of interactions or organisms between each other and their
      environment (feeding, competition, predation). In the end of summer these
      processes are terminated by the state of high species diversity, maximum species
      coordination, expansion of inhabited zone within the sediments, and the distinct
      segregation of space and nutrient resources among species (i.e., achievement of
      ecological complementarity). Decrease in light and temperature causes the reverse
      process--weakening of organism coordination and significant simplification of the
      community structure. In general, these changes correspond to the theory of self
      organization in nonequilibrium systems (Prigogine, Stengers, 2001). The most
      important distinction of observed processes from the classical self-organization
      is their cyclic dynamics, i.e. the annual return of community to its most simple
      state at the end of winter.

PMID- 14598529
TI  - [Epigenetic inheritance and its possible role in the evolution of plant species].
AB  - As it is clear now, the level of gene expression in eukariotes is determined
      mainly by chromatin composition. Chromatin structure of a particular gene (it is
      a complex item, which includes nucleosome positioning, histone modifications and
      non-histone chromatin proteins) can be modified externally and is able to be
      inherited mitotically and meiotically. Changes in chromatine structure are the
      basis of so called epigenetic inheritance that occurs without modification of DNA
      sequence. One of the most striking examples of epigenetic inheritance in plants
      is epimutations--stable for many generation's alleles of some genes that do not
      differ in primary DNA structure. Molecular basis of epimutations seems to be DNA
      metylation. Epimutations may be widely distributed in nature and affect some
      basis morphological features that have a systematic significance. Possibility of
      inheritance of acquired epigenetic modifications lead us to reconsider an idea of
      multipLe independent origins of some plant forms (or ecotypes) under action of
      similar external conditions. Different populations of the same species may in
      this case be unrelated and has no common ancestor. Species should be considered
      as invariant of multiple ways of origin. Wide distribution of polyploids amongst
      higher plants suggests effective mechanism of repression of multicopy genes. Each
      allopolyploidisation event is followed by repression of random set of parent
      genes via changes in its chromatin structure. As a result, in the limits of the
      same hybrid formula may arise different stable combinations of epigenetically
      controlled features of parent species. These combinations may be classified as
      different species of other taxa.

PMID- 14598530
TI  - [Information value of various trinucleotides of some genetic systems].
AB  - New method to reveal the sites in genomes obtaining the high information capacity
      is developed. A distribution of those sites of the length 3 among 16 viral
      genomes and 11 bacteriophages genomes has been studied. It is shown that some
      triplets with high information capacity occur in a family of relatively close
      genomes with the increased frequency. The molecular evolution aspects of a
      persistence of highly scored sites with respect to their information capacity
      among various genomes are discussed.

PMID- 14598531
TI  - [Does Darwinism really contribute to ecology].
AB  - The author questions Ghilarov's (2003) claim that Darwinism has high explanatory
      power in ecology. He is agree with S.V. Meyen who believed that beside synthetic
      theory of evolution (the popular variant on Darwinism) other explanations of
      evolution are possible. It is emphasized that several processes (e.g.,
      diversification and unification of species at one trophic level, as well as
      individual and diffusive coadaptations of species of different levels) can
      contribute to community evolution. Communities cannot be considered as units of
      natural selection.

PMID- 14598532
TI  - [Darwinism as a constraint of ecological pluralism].
AB  - In his respond to critical remarks of Mirkin (2003), the author claims that
      pluralism in ecology is not only its strength but also a weakness. Contemporary
      ecology became less pluralistic and this can be considered as good sign of
      maturing science. Ecological pluralism can be exemplified by the coexistence in
      1920-30s of two different approaches to plant community: that of Frederic
      Clements in USA and that of Josias Braun-Blanquet in France. However the way to
      progress in this branch of ecology was paved rather by heretical ideas of Henry
      Gleason in USA and Ramensky in Russia (both authors independently developed non
      holistic view of community as an assemblage of individualistically distributed
      species) than by "peaceful" coexistence of well-established schools,
      representatives of which tried not to interfere into argumentation of each other.
      Notable success in ecology of last decades was connected with several new
      methodologies, e.g. macroecology that concerned large scale of space and time.
      However Darwinism in its attempt to explain the order of nature referring to its
      origin remains the most universal and fruitful methodology of ecology. The
      success of Darwinism in ecology is understandable because this generalizing
      theory is based on the same universal principles that underlie the survival of
      any population. Ecologists and evolutionary biologists trying to understand
      various natural patterns actually deal with the same fundamental laws, i.e.
      exponential population growth, limitation of this growth by resource shortage
      and/or press of predators, the existence of individual variability in survival,
      etc.

PMID- 14598533
TI  - [Quality of long-term oral anticoagulation: an observation study].
AB  - The aim of this observation study was to analyse the quality of the oral
      anticoagulation in a non-randomised field. Prospectively all patients with an
      oral anticoagulation were registered when entering the hospital. An assessment
      was made of the indication for the oral anticoagulation, the co-medication
      (especially the ones that influence the effect of the anticoagulation), the
      current International Normalized Ratio (INR), as well as any possible
      complications. All INR values were taken from the personal anticoagulation card
      of the patient. 140 patients were identified for the study. 16% of these patients
      had no obvious indication for an oral anticoagulation. Of the 1278 registered INR
      values, 582 (46%) were within the recommended range, according to the common
      guidelines. 359 (28%) INR values were too high and 337 (26%) were too low. 39
      (28%) anticoagulation cards had been kept with the prothrombin time instead of
      INR measurements. The results of this observation survey show that the quality of
      the oral anticoagulation in a non-randomised field is mostly insufficient.

PMID- 14598534
TI  - [Pharmacotherapy of generalized anxiety disorder: state of the art].
AB  - A large percentage of patients in primary care suffer from Generalized Anxiety
      Disorder (GAD). A task force of the Swiss GAD Society has reviewed the scientific
      literature and has developed treatment recommendations. Basic treatment,
      adjunctive treatment and therapy of specific problems like insomnia and
      comorbidities are differentiated. Newer antidepressants are recommended as basic
      treatment, especially venlafaxine and paroxetine, which are licensed for that
      indication.

PMID- 14598535
TI  - [Arteriosclerosis -- an autoimmune disease?].

PMID- 14598537
TI  - Massachusetts city attempts to import drugs form Canada.

PMID- 14598536
TI  - [Recurrent pulmonary infections and "failure to thrive" in a 23-year-old
      man..Large, hemodynamically relevant ASD II].

PMID- 14598539
TI  - Some HMOs see dividends in charging deductibles.

PMID- 14598538
TI  - Pain management. Health plans need to take control.

PMID- 14598540
TI  - Pay incentives to physicians for filing electronic claims.

PMID- 14598541
TI  - Shining light or shipwreck?

PMID- 14598542
TI  - Tough negotiations in store between plans and hospitals.

PMID- 14598543
TI  - Making water run downhill.

PMID- 14598544
TI  - Plans and purchasers team up to manage kidney disease.

PMID- 14598545
TI  - [Vladimir Sergeevich Rusinov (1903-1995)].

PMID- 14598546
TI  - [Intracerebral EEG functioning as a reflexion of the systemic brain organization
      in norm and pathology].
AB  - The authors summarized the EEG findings and defined the nature of intercentral
      EEG relationships in different functional states of healthy subjects and patients
      with organic cerebral pathology based on coherence analysis. The EEG features
      typical of healthy subjects were identified: an anterior-posterior gradient of
      the mean coherence and the character of cortical-subcortical relationships in the
      anterior cerebral structures. Right- and lefthanded subjects showed the frequency
      and regional differences in EEG coherence, which reflected, mainly, specific
      intracortical relationships. Development and regression of pathologic signs in
      right- and lefthanded patients with organic brain lesions are thought to be
      determined by these differences. As distinct from cortical pathology, lesions of
      regulatory structures (diencephalic, brainstem, and limbic) were shown to produce
      more diffuse changes in intercentral relationships with a tendency to
      reciprocity. Intercentral relations, including their interhemispheric
      differences, varied with changes in the functional state of healthy subjects
      (increase and decrease in the level of functioning). A certain time course of
      changes in intercentral relationships was also revealed in patients with organic
      brain lesions during recovery of their consciousness and mental activity. Changes
      in the dominance of activity of individual regulatory structures are considered
      to be one of the most important factors that determine the dynamic character of
      EEG coherence.

PMID- 14598547
TI  - [EEG coherence analysis in music listening].
AB  - Changes in EEG coherence were studied in subjects without special musical
      education when they were listening to low classic music (below 30 dB). The
      numbers of significant changes in coherence function in the left and right
      hemispheres were different. Predominant increase in coherence in the alpha 2,
      beta 1, and beta 2 frequency ranges was observed in the right temporal-central
      and parietal-occipital cortical areas. The left-hemispheric coherence was
      predominantly, decreased on the account of its decrease in the alpha range.

PMID- 14598548
TI  - [Post-radiation effect on the interhemispheric asymmetry in EEG and thermography
      characteristics].
AB  - Complex analysis of EEG and thermographic parameters carried out in 10 healthy
      subjects and 34 patients, Chernobyl clean-up participants revealed a correlation
      between EEG and brain temperature changes in the baseline state and during mental
      arithmetic. During cognitive activity the maximal increase in the average EEG
      coherence and temperature shifts in healthy subjects were observed in the left
      frontotemporal and right parietotemporal areas. In patients changes in both
      parameters under study were most pronounced, the interhemispheric relations were
      impaired. The visual analysis revealed "flat" and "hypersynchronous" EEG types in
      patients. The dominant pathologic activity in the betal range indicative of
      mediobasal and oral brainstem lesions was characteristic of the flat EEG. This
      type of activity was observed in 60% of patients. In these cases, a general
      decrease in EEG coherence and temperature was most pronounced in the left
      hemisphere. The hypersynchronou EEG type (40% patients) was characterized by
      paroxysmal activity in the theta and alpha ranges suggesting diencephalic brain
      lesions. In these cases, EEG coherence and temperature were more variable;
      changes in the right hemisphere were significant, be it increase or decrease. Our
      complex approach to investigation of brain activity in different aspects seems to
      be promising in estimation of the brain functional state both in healthy persons
      and patients in remote terms after exposure to radiation. The specific
      hemispheric temperature changes revealed in Chernobyl patients especially during
      cognitive activity can be the sequels of postradiation disorders of vascular
      neuro-circulation. The EEG findings suggest subcortical disorders at different
      levels (diencephalic or brainstem) and functional failure of the right or left
      hemispheres in remote terms after exposure to radiation.

PMID- 14598549
TI  - [Motor polarization dominance and "animal hypnosis"].
AB  - Two kinds of dominanta were simultaneously formed under conditions of chronic
      experiments in rabbits. The motor polarization dominanta was formed under
      exposure of the right sensorimotor cortex of an animal to direct anodic current,
      and the state of "animal hypnosis" (the second dominanta) was induced. Animal
      behavior and electrophysiological characteristics were recorded. It was shown
      that the "animal hypnosis" induced at the optimum of the right motor polarization
      dominanta inhibited the motor reaction of the "dominant" extremity to testing
      stimuli. After the "animal hypnosis session, exposure of the right sensorimotor
      cortex to anodic current produced the latent excitation focus, which did not
      reach the level of summation. Two days later, exposure to testing stimuli
      developed the latent foci at first in the right cortex and then in subcortical
      structures. In the course of recovery of the motor polarization dominanta and its
      further change for the state characteristic of the "animal hypnosis", the
      patterns of cortical EEG coherence in the delta range typical of each kind of
      dominanta alternated in parallel with the time course of state changes.

PMID- 14598550
TI  - [The structure of dependent relationship between neurons in the sensorimotor
      cortex of the left and right hemisphere in rabbits during immobilizing
      catatonia].
AB  - Relations between activities of neurons simultaneously recorded in the left and
      right sensorimotor brain cortices of rabbits were analyzed in a series of
      experiments before the induction of the immobilization state ("animal hypnosis"),
      in the state of immobilization, and after its termination. The total baseline
      percent of significant correlations between activities of neighboring (within 50
      microns) neurons in the left hemisphere was significantly lower than in the right
      hemisphere. This characteristic of the left hemisphere changed neither in the
      immobilization state nor after its termination. In the right-hemisphere cortex,
      the total percent of correlations between neighboring neurons significantly
      decreased during immobilization and returned to the baseline level after the
      termination of this state. In contrast, percent of correlations between the
      activities of remote (within 500 microns) neurons in the right-hemisphere did not
      change during immobilization, whereas in the left cortex it changed significantly
      and reached its baseline level after the normalization of rabbit's state. Further
      analysis showed that the revealed cortical interhemispheric asymmetry is
      underlain by asymmetric activities of individual neurons and small neuronal
      populations. Thus, for example, changes in the structure of interneuronal
      correlations in cortical microareas of the left and macroareas of the right
      hemispheres could be of different directions, whereas correlated activities in
      microareas of the right and macroareas of the left-hemispheres could change
      synergetically. In other words, asymmetry was revealed at different levels of
      neuronal integration (neuronal pairs, micro- or macrogroups of neurons). This
      finding testifies to a mosaic character of neuronal activity, which finally
      results in the general functional asymmetry during the "animal hypnosis". Certain
      changes in the structure of functional relations between neurons of the
      sensorimotor cortex that developed in the state of "animal hypnosis" persisted
      and even augmented after the termination of this state.

PMID- 14598551
TI  - [Lengthy unilateral EEG changes in alert rabbits after a spreading single
      depressed wave].
AB  - Effects of a single wave of the cortical spreading depression (SD) on the ECoG of
      a waking rabbit was studied with chronically implanted intracortical calomel and
      silverball epidural electrodes. DC potential shifts and integral electrical
      activity were recorded monopolary in reference to a nasal-bone electrode. ECoG
      spectral analysis (FFT) showed that an SD wave was accompanied by a suppression
      of the neocortical activity in a broad frequency range (0.25-80 Hz). However, the
      SD-related ECoG depression was a rather short phenomenon (5-7 min) as compared to
      a following rebound effect, i.e., persistent (1.5-2 h) unilateral exaltation of
      bioelectrical activity. The spectral power in the delta (6-14 fold) and beta
      bands (2-6-fold) increased, whereas the high-frequency activity (40-80 Hz)
      remained suppressed. Similar changes in the contralateral neocortex were poorly
      pronounced or absent; this resulted in a strong interhemispheric asymmetry. It is
      suggested that (1) exaltation of the delta activity after SD wave is related not
      only to a dendrite swelling and changes in the extracellular space structure but
      to increase in synaptic transmission efficiency, probably, by the type of anoxic
      potentiation, (2) activation of some subcortical structures by the mechanism of
      their release from the inhibitory neocortical control is an additional factor of
      the augmentation of the delta and spindle-like beta activity after an SD wave,
      and (3) the long-term attenuation of the high-frequency gamma activity is a
      result of its strong suppression during the SD and its reciprocal relations with
      the exalted delta activity.

PMID- 14598552
TI  - [Modulating influence of adenosine triphosphate on the oscillating properties of
      hippocampal neurons during early ontogenesis].
AB  - Extracellular ATP was used to test the involvement of purinergic P2 receptors in
      the modulation of GAB Aergic giant depolarizing potentials (GDPs) in rat neonatal
      hippocampus. Bath application of ATP reduced the GDP frequency in a concentration
      dependent manner. The inhibitory effect of ATP persisted in the presence of
      adenosine P1 receptor antagonist DPCPX indicating the action of ATP on GDPs. It
      was suggested that, during development, ATP can modulate network-driven activity
      in the neonatal hippocampus through the activation of purinergic P2 receptors.

PMID- 14598553
TI  - [Long-term memory, neurogenesis and novelty signal].
AB  - In accordance with the advanced hypothesis the long-term memory is a collection
      of "gnostic units" selectively tuned to experienced events. The long-term memory
      is continuously supplemented by new neurons differentiated from stem cells during
      neurogenesis (particularly, in adults). The transformation of neuronal
      progenitors into event-selective gnostic units is accomplished with participation
      of hippocampal "novelty neurons" emphasizing information inputs to be stored in
      the long-term memory. The formation of the gnostic units is preceded by
      informational processes occurring in the ventral ("what?") and dorsal ("where?")
      systems. The formation of a new gnostic unit selectively tuned to a particular
      event is a result of combination of feature-detector excitation and novelty
      signal generated by hippocampal novelty neurons.

PMID- 14598554
TI  - [The influence of neuromodulators on the synaptic plasticity in dopaminergic
      structures of the midbrain (hypothetical mechanism)].
AB  - A mechanism underlying the effects of neuromodulators on long-term changes in the
      efficacy of excitatory and inhibitory inputs to dopaminergic and inhibitory cells
      of the substantia nigra and ventral tegmental area is suggested. According to
      this mechanism, activation of Gi/0 protein-coupled dopamine D2 autoreceptors and
      opioid kappa (mu) receptors on dopaminergic (inhibitory) cells promotes the LTD
      of excitatory inputs to these cells and decrease in their activity. Activation of
      Gq/11 protein-coupled alpha1 adrenoreceptors, muscarinic M1, neurokinin NK3
      (alpha1, M3, NK1, serotonin 5-HT2) receptors on dopaminergic (inhibitory) cells
      as well as activation of Gs protein-coupled D1 receptors on inhibitory cells
      promotes the LTP of excitatory inputs to these cells and increase in their
      activity. Augmenting (lowering) GABA release can be provided by activation of
      presynaptic D1 and M3 receptors (mu, 5-HT1, and adenosine A1) receptors. Increase
      (decrease) in GABA concentration due to modulation of inhibitory cell activity
      and/or GABA release will promote the induction of LTD (LTP) of excitatory inputs
      to target dopamine cells. The model agree with known experimental data describing
      the involvement of neuromodulators in modification of dopamine cell activity and
      dopamine release. The suggested model can be useful in understanding the
      operation of neuronal networks, which include the basal ganglia.

PMID- 14598555
TI  - [The study of interhemispheric asymmetry in spatial-perceptive problem solving].
AB  - Features of brain interhemispheric asymmetry during solving the spatial
      figurative task (maze model) were studied in men and women with different
      intelligence quotients (IQ). It was shown that during task solving the rate of
      information processing was higher in the right brain hemisphere, and amplitude
      characteristics of the event-related potentials were higher in the left
      hemisphere. No gender and IQ differences in the character of interhemispheric
      interaction were found during the realization of the maze-model task. The results
      testify that the character of hemispheric interaction depends om the task rype
      rather than gender and intelligence level.

PMID- 14598556
TI  - [Analysis of elicited EEG synchronization and desynchronization in emotional
      activation: temporal and topographic characteristics].
AB  - Event-related synchronization (ERS) and desynchronization (ERD) in delta, theta1,
      theta2, alpha1, alpha2, beta1, beta2, beta3, and gamma were measured in 20
      healthy right-handed subjects in response to IAPS stimuli with low, moderate, and
      high arousal reactions. The 62-channel EEG was simultaneously recorded while
      subjects viewed sequentially presented pictures and subjectively rated them after
      each presentation. The results show that emotionally loaded stimuli induced
      higher ERS in the delta, theta1, theta2, beta1, beta3, and gamma bands along with
      combined ERD and ERS effects in alpha2 band. As to hemispheric asymmetries, the
      effects of emotional arousal were restricted not only to right parietal (theta1
      and theta2 ERS, alpha2 ERD) but also to left frontal (theta2 ERS) regions. In
      terms of affective chronometry, lower theta was the first to catch the affective
      salience of incoming stimuli (time window 0-600 ms after the stimulus input). For
      theta2, alpha2, and gamma bands this process was delayed to 600-1000 ms.

PMID- 14598557
TI  - [Spectral EEG characteristics in students with different anxiety profile during
      tests].
AB  - EEG spectral power was calculated in 39 students at the age of 19-21 years in two
      experimental conditions: during the common educational process and immediately
      before an examination (stress condition). During the education process, in
      subjects with high anxiety (tested by Spielberger) the relative spectral power of
      the delta activity was higher than in the other group in the occipital, parietal,
      central, and right frontal brain areas, whereas the power of the EEG alpha in
      these areas was lower. Before examination tests, in subjects with high activity
      the delta power bilaterally increased in the temporal areas, whereas in subjects
      with low anxiety there was a decrease in the alpha rhythm power, especially in
      the right frontal area. In stress condition, the relative power of the delta
      activity in both occipital and temporal, right parietal and central areas was
      higher in subjects with low anxiety, whereas their alpha power was lower in both
      frontal and in occipital, parietal, and temporal areas of the left hemisphere.

PMID- 14598558
TI  - [Alpha-bursts and K-complex: phasic activation pattern during spontaneous
      recovery of correct psychomotor performance at difference stages of drowsiness].
AB  - It is known that phasic activation processes reveal themselves by different
      electrophysiological patterns depending on the sleep depth. Alpha bursts are an
      electrophysiological manifestation of arousal at the initial stage of sleep,
      whereas at the II stage K-complex becomes the main arousal pattern. We have shown
      earlier that during light drowsiness spontaneous recovery of correct psychomotor
      test performance (after an error) by a sitting subject is accompanied by EEG
      alpha bursts. The aim of this work was to study the EEG phasic activation pattern
      at deeper drowsiness during test performance by a subject in a lying position.
      Subjects had to press sensitive button in a lying position with closed eyes with
      self-paced oral counting of pressings. The experiment lasted for 40 min; EEG,
      EOG, and button pressing were recorded. It was shown that recovery of correct
      performance after errors at deeper drowsiness was accompanied by two types of EEG
      phasic activation patterns (PAP-1 and PAP-2). The alpha frequency component was
      always present in both PAP-1 and PAP-2. PAP-1 were observed at early stages of
      drowsiness and consisted of high-amplitude alpha bursts and EEG activity of
      higher frequency. PAP-2 were recorded at deeper stages and consisted of K
      complexes with superposition of PAP-1. At first (medium level of drowsiness) the
      alpha bursts were superposed on the late slow K-complex components. With further
      deepening of drowsiness the early fast components of K-complex were also
      observed. The early appearance of K-complex during test performance at drowsiness
      seems to be associated with the urgent run of brain arousal systems, which at
      spontaneous falling asleep are in operation at the II sleep stage.

PMID- 14598559
TI  - [Effects of temperature on respiration defensive behavior and locomotion of fresh
      water snail Lymnaea stagnalis].
AB  - Temperature dependence of lung respiration, defensive behavior and locomotion of
      Lymnaea stagnalis snail was studied. At the temperature in the range of 4-6
      degrees C the rates of locomotion and respiration were reduced (as compared to
      control temperature of 14-16 degrees C), whereas defensive reactions were much
      more intense. Vice versa, the temperature rise to 24-26 degrees C activates
      respiration and locomotion but inhibits defensive behavior. It is suggested that
      the observed changes in Lymnaea behavior result from temperature-dependent
      reactions of neurons underlying these activities.

PMID- 14598560
TI  - [C-fos topography in neocortical neurons of mice during fear conditioning].
AB  - Patterns of expression of c-Fos transcription factor in the motor (M1 and M2) and
      cingulate cortex (dorsal part, Cg1, RSA, and ventral part, PrL, Cg2, RSG) were
      analyzed after fear conditioning in 129 sv mice. Mice were exposed to the context
      and tone followed by electric footshock (footshock group, FG) or to context only
      (context group, CG). Control mice were taken from a home cage (HG). In the
      rostral part of the motor cortex the number of c-Fos-labeled neurons was the same
      in all the groups. It was increased in the rostrocaudal direction in FG and CG
      but not in HG mice. A higher level of c-Fos expression in FG (as compared to CG)
      was observed in the medial parts of the M1, in the caudal and medial parts of the
      M2, and in the dorsal but not ventral regions of the cingulate cortex. Thus, the
      rostrocaudal gradient of c-Fos expression was originally demonstrated in motor
      cortex of mice during learning.

PMID- 14598561
TI  - [Application of the function of the number of states of dynamic system to
      investigation of electroencephalographic reaction to photostimulation].
AB  - A new way of EEG analysis is developed, which makes it possible to reveal a
      reaction of the brain cortex to external stimulation at a low response level. The
      method is based on the creation of an image of the EEG curve in the discrete
      phase space and comparison of a current condition with the conditions from a
      certain basic set. The strength of reaction to external stimulation is defined by
      the incidence of conditions novel with respect to the basic ones.

PMID- 14598562
TI  - AIDS vaccine development: the long and winding road.
AB  - Development of a vaccine that provides sterilizing immunity against HIV infection
      remains an elusive goal, due primarily to the difficulty in generating
      neutralizing antibodies to primary HIV isolates. In lieu of a present solution to
      this problem, recent approaches to develop vaccines against HIV/AIDS have focused
      not on preventing infection outright, but on eliciting potent antiviral CD8+ T
      cell responses to limit HIV replication in individuals who become infected after
      vaccination. Successful control of HIV replication in vivo, enabled by vaccine
      elicited immune responses should, in turn, attenuate an individual's rate of
      progression to AIDS while reducing their likelihood of subsequently transmitting
      HIV. Recent pre-clinical evaluation of CTL-based vaccines in non-human primate
      models of AIDS has shown several different vaccine modalities (e.g. heterologous
      'prime/boost' strategies such as DNA + recombinant viral vectors) to be capable
      of eliciting high-level cellular immune responses that are associated with
      limitation of virus replication and protection against disease following
      challenge with select pathogenic virus isolates. However, it is not currently
      known to what extent these protective effects, observed under optimal
      experimental conditions in select animal models, can be translated into relevant
      protection of humans against AIDS. In this article we discuss the promise,
      potential limitations, and scientific challenges that currently provide the
      context for efforts to develop and successfully employ a safe and effective AIDS
      vaccine.

PMID- 14598563
TI  - Worldwide transmission of drug-resistant HIV.
AB  - The availability of highly active antiretroviral therapy (HAART), that suppresses
      replication of the human immunodeficiency virus type 1 (HIV-1), has dramatically
      improved the prognosis of HIV-infected patients. In populations with access to
      HAART, the course of the infection has changed from an inevitably fatal disease,
      characterized by a high incidence of opportunistic infections, into a potentially
      treatable chronic condition. Unfortunately, HAART does not durably suppress HIV
      replication in 20-50% of treatment-naive patients and in up to 50-70% of
      treatment-experienced patients. In the majority of patients with viral rebound,
      drug-resistance-related mutations are detected. New infections through
      transmission of drug-resistant strains to individuals who have never been exposed
      to therapy are now being increasingly reported, despite all HIV prevention
      efforts. Moreover, recent reports correlate new infections by drug-resistant
      virus with suboptimal therapy response, which raises major public health
      concerns. Despite a large number of publications on the rate of primary
      resistance, it is very difficult to draw general conclusions. The large variation
      in methodology and interpretation illustrates the need for systematic approaches.
      Global surveillance is urgently warranted to monitor the circulating HIV-strains.
      In addition, follow-up research has to be performed to reveal the impact of drug
      resistance on future therapy options. This paper reviews current literature to
      elucidate the mechanisms, implications and magnitude of transmission of drug
      resistant HIV-1.

PMID- 14598564
TI  - Post-entry restriction of retroviral infections.
AB  - Pathogenic retroviruses have driven the evolution of several dominant-acting
      mechanisms able to block infection and protect the host. These are exemplified by
      the mouse gene Fv1, which encodes a Gag-like protein able to protect against
      murine leukemia virus (MLV) infection. The block is saturable, occurs after
      reverse transcription and is directed against the viral capsid gene. Several
      other mammalian species are also able to block MLV infection with the same capsid
      specificity. A human gene with this activity has been named Ref1. Recently,
      primates have been shown to restrict a variety of retroviruses only very
      distantly related to MLVs through a gene named Lv1. Restricted viruses include
      MLV as well as lentiviruses such as human immunodeficiency viruses 1 and 2,
      simian immunodeficiency virus and equine infectious anemia virus. In each case
      the block to one retrovirus can be saturated by co-infection with a second
      restricted virus. The possible mechanisms of action, and evolutionary
      consequences of restriction, are reviewed.

PMID- 14598565
TI  - Protease inhibition in African subtypes of HIV-1.
AB  - Of the 42 million people infected with HIV-1 worldwide, 30 million are in Africa.
      However, the HIV-1 subtypes prevalent in Africa are not the same that are
      prevalent in North America and Western Europe. In these developed regions,
      subtype B is responsible for the vast majority of HIV infections, whereas in sub
      Saharan Africa subtypes A and C, and to a lesser extent subtype G, account for
      most of the infections. These subtypes exhibit genomic differences as large as
      30% with respect to subtype B. These differences involve current drug targets,
      including the HIV-1 protease. Since protease inhibitors have been developed and
      tested against the HIV-1 B subtype, and proteases from other subtypes carry up to
      ten amino acid polymorphisms, it is important to assess the influence of these
      naturally occurring polymorphisms on the potency of existing inhibitors, as well
      as their synergistic interactions with mutations known to cause drug resistance.
      This review will examine the effects of naturally occurring polymorphisms on the
      efficacy of current protease inhibitors and the effects of well characterized
      drug-resistant mutations within the framework of non-B subtypes. At the
      biochemical level, non-B-subtype polymorphisms lower the binding affinities of
      existing clinical inhibitors, but not to the point of causing drug resistance.
      However, these polymorphisms amplify the effects of mutations causing drug
      resistance and may play a role in the long-term viability of these inhibitors.

PMID- 14598566
TI  - Disrupting T-cell homeostasis: how HIV-1 infection causes disease.
AB  - In the absence of antiretroviral treatment, HIV-1 establishes a chronic infection
      that is marked by the progressive depletion of CD4+ T-cells. Of all the viral
      infections that afflict humans, only HIV-1 is known to cause such profound and
      inevitable CD4+ T-cell loss. Yet the mechanisms by which this depletion arises
      remain a matter of controversy. This review will address what is exceptional
      about HIV-1 infection that sets it apart from other viral infections. Recent
      attempts to understand HIV-1 pathogenesis have set aside the view that CD4+ T
      cell depletion is effected solely by HIV-1-mediated killing in favor of a more
      complete explanation that also includes T-cell dynamics and, more specifically,
      chronic immune activation as a central factor in HIV-1 pathogenesis. This review
      will address the contributions of the virus itself, T-cell activation, T-cell
      reconstitution, and target cell availability, in the shaping of these dynamics
      during the disease. The acute and chronic phases of HIV-1 disease will be
      addressed separately, as they manifest distinctive viral and T-cell dynamics and
      are the setting for different pathogenic mechanisms. New observations suggest
      that considerable damage is caused to the immune system during the acute phase of
      the infection, resulting in a substantial early lymphopenia of the memory CD4+ T
      cell pool that may have a profound impact on the subsequent course of the
      infection. Other observations reveal a strategy in which HIV-1 induces immune
      activation to generate replaceable targets, activated CD4+ T-cells, which sustain
      its replication. Although the majority of these target cells are short-lived by
      physiological design, chronic activation can indirectly strain homeostasis of the
      naive and resting memory T-cell pools in a number of ways. In the context of
      virus-induced damage to the lymphoid tissues and cells that maintain these T-cell
      pools, and physiological limitations in peripheral CD4+ T-cell renewal, this
      homeostatic strain leads to the progressive depletion of the more vulnerable CD4+
      T-cell pools.

PMID- 14598567
TI  - Adenoviruses as vectors for HIV vaccines.
AB  - The tropism of adenoviruses (Ad) for mucosal epithelium makes them ideal vectors
      for the development of recombinant Ad-HIV vaccines. Currently, several Ad-HIV
      vaccine candidates are being tested in clinical and preclinical trials. Here, we
      review the progress on the safety, immunogenicity and efficacy of replication
      competent and replication-defective Ad-HIV and Ad-SIV vaccines in animal models,
      including non-human primates. Replication-defective Ad-SIV gag vaccines have
      elicited cellular responses that control intravenous infection with an HIV/SIV
      chimeric immunodeficiency virus (SHIV), while replication-competent Ad-SIV
      env/rev/gag/nef vaccines have stimulated cellular and humoral responses and
      protected rhesus monkeys from a mucosal challenge with pathogenic SIV. The
      composition and advantages of these and other Ad vaccines are described, with
      particular emphasis on strategies to increase the immunogenicity of the
      replication-defective vaccines and the safety and efficacy of the replication
      competent approach. The overall efficacy of Ad-based vaccines in non-human
      primates should encourage further evaluation of additional replication-competent
      and replication-defective Ad-HIV candidates in human trials.

PMID- 14598568
TI  - [Tenascin-C expression in human breast tumors].
AB  - INTRODUCTION: Increased amounts of extracellular matrix proteins have been
      described in breast tumours, which are normally present in embryonal connective
      tissue, in adults however, these occur only in pathological conditions: one of
      which is tenascin. Within the tenascin family the most examined and most
      controversial member is tenascin-C. It has been suggested that tenascin-C
      decreases cell adhesion, promotes invasion and metastases, and may play role in
      pathological angiogenesis. MATERIAL AND METHODS: Authors investigated 62 primary
      breast carcinomas and in further 20 cases both the primary and the recurrent or
      second primary tumours were examined. In the latter group the main question was
      whether tenascin-C was of prognostic significance. The newly formed vessels were
      visualised using CD31 antibody. RESULTS AND CONCLUSIONS: Tenascin-C positivity in
      the tumour cells was shown in the 10 of the 62 primary carcinomas and in 7 from
      the second group of cases (20 patients). Of all cases examined, in five specimens
      tenascin-C positivity was present in normal ductal epithelial cells. In variable
      amount, in the stroma of invasive tumours, tenascin-C was present in every case.
      The presence of tenascin-C within tumour cells, at the periphery and also in the
      stroma of tumours, within the proliferating ducts, around tumour cell nests and
      in situ carcinomas, furthermore, in the epithelial cells of normal ducts suggests
      that tenascin-C may promote detachment and migration of carcinoma cells. There
      was no correlation, however, between tenascin-C expression and the occurrence of
      recurrences in this small group. Correlation was found between increased stromal
      tenascin-C expression and angiogenesis. Authors conclude that tenascin-C might
      have a role in angiogenesis.

PMID- 14598569
TI  - [Is type-2 diabetes mellitus preventable?].
AB  - The public health burden of type 2 diabetes mellitus has been dramatically
      increased worldwide. Not only its prevalence rate at present but the increase of
      its incidence in the near future can create a global health problem. The rapid
      increase of the total number of newly diagnosed diabetic patients proved to be
      associated with the increasing prevalence rate of obesity. The metabolic syndrome
      and type 2 diabetes can contribute to accelerated atherosclerosis and, therefore,
      the target organ damages can carry a serious problem for the individuals and also
      for the whole society. It is obvious, that the primary prevention of type 2
      diabetes mellitus is of great importance. There is now substantial evidence that
      type 2 diabetes can be prevented or delayed by lifestyle interventions, i.e. diet
      and exercise should be the first choice in order to avoid weight gain when
      preventing diabetes. Pharmacological intervention should not be routinely used to
      prevent diabetes although results of large clinical trials with metformin and
      acarbose in subjects with impaired glucose tolerance are available. It is
      noteworthy that a decrease in the number of newly diagnosed diabetes was observed
      in prospective, double blind clinical studies evaluating the effect of new
      antihypertensive drugs (captopril, ramipril, lisinopril, nifedipine GITS,
      amlodipine, losartan) or lipid-lowering agents (pravastatin) on the
      cardiovascular morbidity and mortality in high risk patients. In these studies
      the relative risk reduction of newly diagnosed diabetes was evaluated in
      comparison to placebo or other drugs in a subgroup of non-diabetic patients at
      baseline. In addition, the incidence of newly diagnosed type 2 diabetes decreased
      parallel with weight loss in clinical trials with orlistat, an anti-obesity drug.
      Although new results were provided by evidence based clinical trials a lot of
      questions remained to be solved. Further research is necessary to understand
      better how to facilitate effective primary prevention of type 2 diabetes. Further
      data are needed to evaluate the clinical significance of currently used
      antidiabetic drugs and, in addition, the possible role of other drugs
      (antihypertensives, lipid lowering agents, anti-obesity drugs) should also be
      investigated in order to identify the optimal primary prevention policy of type 2
      diabetes.

PMID- 14598570
TI  - [Erosive polyarthritis in a patient with agammaglobulinaemia. Primary
      immunodeficiency diseases with rheumatic manifestations].
AB  - This article reviews the most common forms of primary immunodeficiencies with
      articular involvement: X-linked (Bruton's) agammaglobulinaemia, common variable
      immune deficiency and selective IgA deficiency. The most commonly observed types
      of arthritis in these disorders are benign, aseptic, characteristically non
      erosive polyarthritis and infective arthritis caused by Mycoplasmas or
      Ureaplasmas. The authors present the case of a patient with immunodeficiency
      whose polyarthritis was found to be unusually severe and destructive.

PMID- 14598571
TI  - [Correlation of lower extremity Doppler index with flow-mediated vasodilation and
      the extent of coronary disease].
AB  - AIMS: The aim of this study was to examine relationship between resting ankle
      brachial pressure index and flow mediated vasodilation, and that of the extent of
      coronary artery disease. PATIENTS AND METHODS: Authors examined 77 subjects. All
      had peripheral arterial disease (with ankle-brachial pressure index less than
      0.8), and angina pectoris (coronary artery disease verified by coronary
      angiography). Mean age was 64.6 years (range 41-82 years). Flow mediated
      (endothelial dependent) vasodilatation was measured for all participiant.
      RESULTS: Authors stated, that ankle-brachial pressure index significantly
      correlates with flow mediated vasodilatation and the same connection can be
      supposed between Doppler index and coronary artery disease's extension.

PMID- 14598572
TI  - [Screening for dementia syndromes: the Hungarian experience with the 7-Minute
      Test].
AB  - INTRODUCTION: The screening and recognition of dementing disorders are considered
      as important tasks of general practitioners. Despite of the recent progress made
      in the treatment of cognitive, behavioral symptoms and slowing down the rate of
      progression, difficulties are still existing in the early detection, and the most
      frequent dementia forms such as Alzheimer's disease (AD) and vascular dementia
      (VD) are underdiagnosed in Hungary. Any rapid, easy-to-use dementia screening
      method therefore could be of great value in the community. AIMS: The Hungarian
      standardisation of a new dementia screening tool, the 7 Minute Test (7MT) has
      been reported here. Accuracy, sensitivity and specificity were calculated. The
      authors provide new data regarding the discriminative power of this test in a
      variety of dementing and dementia related conditions. METHODS: The test results
      of 339 probands, referred to the local memory clinic, were evaluated in all
      subtests, where orientation in time, memory, verbal fluency, and
      visuoconstructive skills are assessed. The patients were clustered into seven
      groups according to their clinical diagnosis, such as: Control (CNT), Mild
      Cognitive Impairment (MCI), AD, VD, mixed AD-VD, depression (D) and Organic
      Amnestic Syndrome (OAS). RESULTS: In overall, the test successfully discriminated
      77% of the CNT and all disease cases (sensitivity 85%, specificity 55%). When the
      AD and CNT groups were compared separately, the highest values: 91% sensitivity,
      86% specificity have been found. A total score of 139 has been suggested as a
      cutoff value to separate CNT and dementia cases. These results suggest that the
      test is suitable to classify CNT and "real" dementia cases (AD, VD, mixed AD-VD),
      but not valid within the real dementia groups. Furthermore, it is not helpful for
      the identification of MCI, pseudodementia cases (D) and OAS as well. CONCLUSION:
      The 7MT could be a valuable dementia screening tool in the primary care, but it
      is not specific for any form of dementia.

PMID- 14598573
TI  - [Chronic venous insufficiency].

PMID- 14598574
TI  - [Medical terminology--our common cause].

PMID- 14598575
TI  - [Veterinary medicine and public health or better: veterinary public health].
AB  - The development of veterinary medicine and its impact on public health are
      outlined in this overview. In relation to this, we speak of Veterinary Public
      Health. In 1865, the liberal J.R. Thorbecke initiated the institution of the
      later independent 'State Supervisory Public Health Inspectorate' was set up in
      1920, as a consequence of the Meat Inspection Act of 1919, and became part of the
      State Supervisory Service. In 1925 the 'Veterinary Public Health Inspectorate',
      which was part of the Ministry of Public Health, and the 'Veterinary Service',
      which was part of the Ministry of Agriculture, formed together a so-called
      'Personal Union'. This Union came to an end in 1984. During the nearly 60 years
      of its existence, and especially after the Second World War, the Union has
      contributed enormously to public health by controlling zoonoses and decreasing
      chemical contaminants in foodstuffs. In these achievements it has worked in
      collaboration with veterinary surgeons, meat inspection services, and research
      institutes such as the National Institute of Public Health and Environment
      (RIVM), the Institute for Animal Science and Health (ID-Lelystad), and the
      Faculty of Veterinary Medicine.

PMID- 14598576
TI  - [Laboratory rabbit?].

PMID- 14598577
TI  - [Packaging instructions for diagnostic and infectious materials still valid until
      2005].

PMID- 14598578
TI  - [The financial health of veterinary clinics].

PMID- 14598579
TI  - [Short summary of the final report of the survey, "Name Recognition among
      Veterinarians." Veterinarians take action in cases of large animal abuse].

PMID- 14598580
TI  - [BSE-blood test in living animals].

PMID- 14598581
TI  - [Anecdote].

PMID- 14598583
TI  - [ACTH-ectopic syndrome].

PMID- 14598582
TI  - [The role of tumor necrosis factor in pathogenesis and treatment of sarcoidosis].

PMID- 14598584
TI  - [Etiology and pathogenesis of nonspecific aortic arteritis].

PMID- 14598586
TI  - [Abnormal cerebrovascular reactivity in patients with asymptomatic
      atherosclerosis of the carotid arteries].
AB  - The study included 53 patients (males at the age of 44-78 years) with ischemic
      heart disease and arterial hypertension with asymptomatic unilateral
      atherosclerotic affection of carotid arteries (CA). Ultrasonic investigation
      registered 30-80% stenosis of carotid arteries in the absence of neurological
      deficit. Cerebrovascular reactivity was assessed by means of the hypercapnic
      hypoxic test (HHT) including breathing via additional "dead space" for 3 min.
      Initial and peak linear velocity of the blood flow in the middle cerebral artery
      was measured with ultrasonic transcranial dopplerography. By HHT results, three
      types of cerebral vascular reactions in patients with combined atherosclerosis of
      coronary and carotid arteries were identified: subnormal dilatation on the side
      of stenosed internal carotid artery, increased dilatation and paradoxical
      vasoconstriction on the affected side. Cerebrovascular reactivity and the type of
      atherosclerotic plaques did not collerate.

PMID- 14598585
TI  - [Melatonin: ulcer disease and seasons of the year].
AB  - Melatonin produces a great variety of effects in human organism and plays an
      essential role in normal function of the body. This explains growing interest of
      medical researchers to this substance. The paper provides the results of 3-year
      studies of seasonal rhythm of melatonin production in patients with duodenal
      ulcer. Acute disorders of circadian and seasonal melatonin production in summer
      and autumn were discovered in patients with duodenal ulcer. These findings
      suggest involvement of abnormal melatonin production in pathological mechanisms
      of autumn exacerbations of duodenal ulcer.

PMID- 14598587
TI  - [Antibodies to beta2-glycoprotein I and antibodies to cardiolipin in
      antiphospholipid syndrome: analysis of sensitivity and specificity].
AB  - To study sensitivity and specificity of antibodies to beta 2-glycoprotein I (B2GP
      I) and antibodies to cardiolipin (CL) in diagnosis of antiphospholipid syndrome
      (APS), we examined 19 patients with primary antiphospholid syndrome (PAPS), 23
      patients with secondary APS (SAPS) and systemic lupus erythematosus (SLE) and 73
      patients with SLE. Antibodies to B2GP-I and CL of IgG isotype were measured at
      enzyme immunoassay. The levels of IgG aCL and IgG aB2GP-I in the serum of PAPS
      patients were 69.9 +/- 116.0 GPL, 74.1 +/- 117.4 SGU, respectively; of SAPS and
      SLE patients 60.5 +/- 68.9 GPL and 66.2 +/- 88.3 SGU, respectively. These values
      were significantly higher than in SLE patients (19.5 +/- 27.6 GPL, p = 0.0025 and
      p = 0.0012; 14.5 +/- 41.9 SGU, p = 0.0001, respectively) and donors (3.9 +/- 3.8
      GPL, p = 0.0001; 5.7 +/- 1.2 SGU, p = 0.001). By IgG aCL and IgG-aB2GP-I, PAPS
      and SAPS patients differed insignificantly (p > 0.05), but these values
      correlated positively (r = 0.85; p < 0.0005 for PAPS and r = 0.9, p < 0.005 for
      SAPS). Simultaneous detection of IgG aCL and IgG aB2GP-I occurred in 36.8% in
      PAPS, 52.4% in SAPS and 12.3% in SLE. 10.5% PAPS patients were positive by IgG
      aCL as well as 9.5% with SAPS and 13.4% with SLE. Isolated rise of IgG aB2GP-I
      concentration was observed in 21.1% patients with PAPS, in 9.5% patients with
      SAPS and 9.6% patients with SLE. Of 43 patients with a history of thrombosis,
      46.5% were positive by IgG aCL and IgG aB2GP-I, 7.0% positive only by IgG aCL and
      11.6% only by IgG aB2GP-I. Levels of IgG aCL and IgG aB2GP-I in patients with
      thrombosis (64.7 +/- 87.5 GPL and 66.0 +/- 94.8 SGU, respectively) were
      significantly higher than in patients without them (19.6 +/- 3.8 GPL, p = 0.009
      and 16.4 +/- 52.2 SGU, p = 0.0001). In venous thrombosis IgG aCL and IgG aB2GP-I
      were higher than in arterial thrombosis (p < 0.004). For diagnosis of APS
      sensitivity and specificity of IgG aB2GP-I and IgG aCL were 60.0 and 83.8%; 57.1
      and 73.5% (p > 0.05), respectively. As to thrombosis, the sensitivity and
      specificity were 58.1 and 84.6%; 54.5 and 72.7% (p > 0.005), respectively. Thus,
      IgG aB2GP-I is an essential additional marker of APS. In the presence of APS
      symptoms, but in negative results of APS test it is justified to confirm APS
      diagnosis by aB2GP-I test results. To make APS diagnosis more accurate, it is
      valid to make simultaneous measurements of aCL using standard B2GP-I dependent
      enzyme immunoassay and aB2GP-I.

PMID- 14598588
TI  - [Diagnostic implications of detecting antibodies to angiotensin-converting enzyme
      and its substrates].
AB  - The results of the analysis of diagnostic significance of examination of natural
      antibodies (Nab) to agiotensin-converting enzyme (ACE) and its substrates in the
      serum of hypertensive patients indicate that concentration of Nab to ACE differ
      from this mean concentration in donors. An elevated level of Nab to ACE may be
      considered as a compensatory reaction to increased content of the enzyme in
      vascular endothelium and blood flow. The same patients were examined for
      antibodies to peptide angiotensin II (AT-II). Enzyme immunoassay has shown that a
      significantly elevated level of antibodies to AT-II was only in 5 examinees. The
      same patients had also high Nab to ACE. The study of a group of ischemic heart
      disease patients with adverse effects attributed to bronchial affection treated
      with enalapril and diroton (ACE inhibitors) demonstrates that deterioration of
      cough and external respiration function is not related to exacerbation of
      existing chronic pulmonary inflammation. None of the patients had elevated body
      temperature or inflammatory changes in the blood, other signs of inflammation.
      Enzyme immunoassay also proved that the initial level of Nab equaled mean value
      for donors or was insignificantly lower. Blood serum patients with side effects
      contained a significantly (p < 0.02) elevated quantities of Nab to bradikinin vs
      initial values. Thus, the proposed method of solid phase enzyme immunoassay
      quantifies Nab to ACE and its substrates in the patients.

PMID- 14598589
TI  - [Central and peripheral hemodynamics in patients with essential hypertension on a
      fasting diet].
AB  - Effectiveness of an antihypertensive action of fasting therapy was studied in 147
      patients with arterial hypertension stage I-II. Estimation of systolic and
      diastolic functions of the left ventricle in patients with arterial hypertension
      was carried out using stress echocardiography with isometric loading. Dynamics of
      systolic and diastolic arterial pressure (AP) and changes in the hyperbaric index
      for diastolic AP were assessed at 24-h AP monitoring. The course of fasting
      therapy consisting of a 2-week fasting period and the recovery period of the same
      duration resulted in a statistically significant reduction of weight, a decrease
      of average daily systolic and diastolic AP, lowering of the hyperbaric index of
      diastolic AP and improvement of the diastolic reserve of the left ventricle. 24-h
      AP monitoring and stress echocardiography within 3 months showed a high clinical
      effectiveness of fasting therapy.

PMID- 14598590
TI  - [Atherogenic cholesterol-containing circulating immune complexes--one of the
      components of the serum in patients with systemic lupus erythematosus].
AB  - To estimate concentrations of cholesterol (CS) and immune complexes (IC) in
      patients with systemic lupus erythematosus (SLE), we examined 20 new SLE cases
      (all women, mean age 30.2 +/- 6.6 years, duration of the disease 2.6 +/- 1.5
      years) with no history of corticosteroids treatment. The control group of 20
      healthy patients was matched by age, body mass index and absence of risk factors.
      CS in IC precipitates was estimated by enzyme assays (kits by Boehrinnger
      Mannheim GmbH, Germany). The level of CS-containing IC (CS-IC) was significantly
      higher in SLE patients (11.9 +/- 2.7 mcg/ml) versus controls (6.0 +/- 2.2 mcg/ml,
      p < 0.05). The lipid spectrum was similar in the patients and controls. A
      significant positive correlation was registered between LDP CS and CS-IC levels
      (r = 0.774; p = 0.041). Association with other indices of blood lipid spectrum
      (total CS, triglycerides, HDP CS) was not observed. Thus, elevated level of CS-IC
      and association with LDP CS may be involved in atherogenesis of SLE patients.

PMID- 14598591
TI  - [Clotting factor VIII in Sneddon syndrome].
AB  - Hyperactivity of coagulation factor VIII (fVIII) marks hypercoagulation. FVIII
      enhances activity of factor IX and their combination activates factor X, which is
      of primary importance in prothrombin transformation into thrombin, on the
      phospholipid membrane. The activity of fVIII was studied in 28 patients (26
      women, 2 men, mean age 49.6 +/- 7.8 years) with Sneddon's syndrome (SS). SS
      manifests clinically similarly to primary antiphospholipid syndrome (PAS). The
      leading of them are ischemic disorders of cerebral circulation (IDCC) and
      advanced livedo present in all the examinees. Hyperactivity of fVIII was
      registered in 21 (75%) of 28 patients. Most of thrombosis-related symptoms
      occurred more frequently in patients with high than normal activity of fVIII:
      ischemic strokes (91% vs 57%, p > 0.05), repeated strokes (71% vs 0%, p =
      0.0014), transient IDCC (76% vs 57%, p > 0.05), vascular dementia (43% vs 0%, p >
      0.05), ischemic heart disease (43% vs 0%, p > 0.05), thickening of heart valves
      according to echocardiography (91% vs 57%, p > 0.05), peripheral venous
      thromboses (24% vs 0%, p > 0.05). In high fVIII activity cardiolipin antibodies
      occurred more rarely (24% vs 43%, p > 0.05) but lupus anticoagulant was seen more
      often (47% vs 14%, p > 0.05). High fVIII activity was in 8 of 12 aPL-negative
      patients. It is demonstrated that elevated fVIII activity is an essential
      mechanism of thrombosis development in SS. The cause of this enhanced activity is
      suggested to be special aPL in interaction with which fVIII becomes insensitive
      to inactivation with protein C. The activity of protein C was normal in all the
      cases.

PMID- 14598592
TI  - [Protein content in blood plasma and its changes in patients of the neurological
      critical care unit].
AB  - Twelve blood plasma proteins were studied in 120 patients with isolated traumatic
      and nontraumatic cerebral hemorrhage. At all stages of the study a marked
      imbalance of blood proteins occurred which was independent of the etiological
      factor. Patients with craniocerebral trauma exhibited the phenomenon of the
      atypical response manifesting with low concentration of acute-phase proteins. The
      levels of the complement component C5 and transferrin in patients with cerebral
      vascular aneurysm rupture are shown diagnostically significant while follow-up of
      blood transtiretin can show the trend in the metabolic processes in patients with
      cerebral hemorrhage in critical condition.

PMID- 14598593
TI  - [Cytokine regulation of immune response in patients with chronic hepatitis C].
AB  - To evaluate content of interleukines (IL-1, IL-2, IL-4 and IL-6) and tumor
      necrosis factor (TNF) in patients with chronic hepatitis C (CHC), 72 CHC patients
      (37 males and 35 females, mean age 37.2 +/- 4.8 years) were examined. The control
      group consisted of 20 healthy donors (mean age 25.5 +/- 2.3 years). It was found
      that low levels of IL-1, IL-2, IL-6, TNF evidence for weak immune response which
      means long-term virus circulation and active replication. The highest
      concentrations of the above cytokines correspond to low replicative activity
      while high IL-4 levels point to active virus replication. IL-1, IL-2, IL-4, IL-6,
      TNF were high in patients with high cytolysis. Cytokine regulation of immune
      response can be used for assessment of the effectiveness of antiviral and
      immunocorrective therapy.

PMID- 14598594
TI  - [Use of proton pump inhibitors in the treatment of gastroesophageal reflux
      disease].
AB  - Gastroesophageal reflux disease (GERD) is a wide spread disease characterized by
      distinct clinical polymorphism manifesting with various symptoms and/or
      inflammatory changes of a distal portion of the esophagus. Current first-line
      therapy in GERD consists in administration of proton pump inhibitors (PPI) which
      promote faster relief of the symptoms and healing of erosive-ulcerous lesions of
      esophageal mucosa in GERD patients. Clinical efficacy of standard and novel PPI
      is compared. Wide use of PPI and their long-term courses require further study of
      PPI side effects which now lack attention from the clinical researchers.

PMID- 14598595
TI  - [Taste affection and its causes].
AB  - Basic anatomophysiological evidence underlying sense of taste, main causes of
      taste disorders, guides for practitioners how to detect these disorders and
      differentiate them with physicians of allied specialities, make prognosis and
      design policy of the disease treatment are reviewed.

PMID- 14598596
TI  - [Rational antibiotic therapy of pneumonia].
AB  - The aim of the study was to analyse antibacterial treatment in patients with
      extrahospital pneumonians in a standard pulmonological department. The analysis
      covered 80 patients with EHP treated in 2000. In the 100% cases the choice of the
      antibiotics was random and did not depend on pneumonia severity, age, sex,
      occupation of the patient, concomitant pathology, the disease duration, previous
      treatment. Gentamycin was prescribed most frequently. The course doses of the
      drugs were often violated. The mean hospital stay was 22.5 days, complete
      resolution was observed only in 8.75% patients.

PMID- 14598597
TI  - [Dilated and ischemic cardiomyopathy: differential diagnosis].
AB  - A uniform set of differential-diagnostic methods was used in 45 patients with
      dilated cardiomyopathy (DCMP) and 36 patients with ischemic cardiomyopathy
      (ICMP). The following parameters, significant for differentiation of the above
      diseases, have been defined: case history data, more deep decrease of global
      myocardial contractility and dilation of cardiac chambers, prevalence of
      increased linear sizes of the right ventricle, reduction of linear sizes of the
      aorta and left ventricular hypertrophy in DCMP; a different direction of left
      ventricular contractility index in dobutamine test.

PMID- 14598598
TI  - [Memorable dates in the history of clinical medicine in 2003].

PMID- 14598599
TI  - The roles of epithelial-mesenchymal interactions and the innate immune response
      on the tumorigenicity of human prostate carcinoma cell lines grown in immuno
      compromised mice.
AB  - BACKGROUND: Animal models are crucial to further our understanding of the
      mechanisms of (progressive) growth of prostatic cancer. MATERIALS AND METHODS: We
      have developed an intravital microscopic model based on the dorsal skinfold
      chamber technique in mice, allowing continuous measurements of growth and
      angiogenesis of small tumor spheroids. A histone H2B-GFP fusion protein has been
      introduced in our cell lines, allowing evaluation of mitotic and apoptotic
      indices. This system was used to evaluate the growth and angiogenesis of LnCAP,
      PC3 and DU145 tumor spheroids. RESULTS: LNCAP spheroids regressed rapidly, with
      complete tumor cell death within 7 days. PC3 spheroids regressed at a slower rate
      demonstrating a high apoptotic rate, though considerably lower than LNCAP. DU145
      spheroids regressed the slowest, demonstrating considerably lower apoptotic rates
      and measurable mitotic rates. CONCLUSION: The inability to effectively the innate
      immune system by encapsulation prevents the survival of small human micro-tumor
      xenografts. Thus, the complex interactions between tumor cells and TAMs, which
      are pivotal in tumor biology, are extensively perturbed by "foreign" human tumor
      cells.

PMID- 14598600
TI  - Predictive value of absent bone marrow iron stores in the clinical diagnosis of
      iron deficiency anemia.
AB  - The examination of Prussian-blue-stained bone marrow aspirates for the presence
      or absence of histiocytic iron granules has been considered the gold standard in
      evaluating iron-depeleted states. We performed this study to evaluate the
      predictive accuracy of absent stainable bone marrow iron for iron deficiency
      anemia (IDA). A retrospective study was performed on an unselected series of 53
      consecutive bone marrow biopsy specimens. Only those patients who had totally
      depleted iron stores and who had iron studies done within 6 months of bone marrow
      biopsy were included in the study. Based on these criteria, 12 patients were
      found eligible. After complete evaluation to determine the cause of the patient's
      illness, the final diagnosis was IDA in only 6 patients (50%). There was no
      significant difference between the two groups as regards hemoglobin level,
      reticulocyte count, serum iron levels, total iron binding capacity, red blood
      cell mean corpuscular volume, ferritin and the transferrin saturation levels. The
      finding of absent bone marrow iron stores is not necessarily predictive of iron
      deficiency anemia. The finding of absent stores of iron in the bone marrow needs
      to be taken in conjunction with other laboratory findings and the clinical
      scenario while making a diagnosis of IDA, since certain other hematological
      diseases may co-exist.

PMID- 14598601
TI  - Structural analysis of physiological degeneration and lysis in the larval tail of
      anuran tadpoles during metamorphosis compared with human histopathology,
      especially myopathology.
AB  - The metamorphotic degeneration of the larval tail of anuran tadpoles was
      investigated for tissue-typical aspects and for correspondences or similarities
      with histopathological findings in human diseases. For this purpose, in ten
      species the premetamorphotic morphology and metamorphotic degeneration of cells
      and tissues in the larval tail was examined light- and electron-microscopically.
      Metamorphotic degeneration and lysis occurs in a tissue-specific manner. Thereby,
      filaments in notochord- and epidermis-cells as well as in the cross-striated
      musculature can aggregate to a variety of different "compact bodies". These
      bodies decompose or are taken up by phagocytizing cells. Collagen fibrils and
      filaments are completely dissolved. Lysed larval tail tissues are resorbed.
      During evolution, tissue typical degeneration patterns have developed in anuran
      tadpoles and, despite systematic differences, these are also recognizable in
      histopathological findings of human diseases, notably myopathies. Structure
      analyses of tissue degradation in metamorphosing anuran tadpoles may well be
      applicable as suitable experimental models for investigating the causes and
      courses of human diseases.

PMID- 14598602
TI  - Interaction of Ginkgo biloba extract (GBE) with hypotensive agent, nicardipine,
      in rats.
AB  - The effect of Ginkgo biloba extract (GBE, 0.5%) orally administered for 2 weeks
      on the antihypertensive action of oral nicardipine was examined in Wistar rats.
      GBE significantly increased hepatic P-450 content and reduced the hypotensive
      effect of nicardipine. GBE administration resulted in a significant decrease in
      maximal nicardipine plasma concentration (Cmax) and the 23-hour area under the
      curve (AUC0-23). Thus, it is suggested that GBE attenuated the therapeutic
      potency of nicardipine, probably secondary to increased hepatic drug metabolism.

PMID- 14598603
TI  - Axial loading MRI of the lumbar spine.
AB  - BACKGROUND: The aim of our study was to evaluate the incoming interrelations
      between chronic low back pain and biomechanical changes of the lumbar spine,
      using an MRI-compatible axial-loading device mimicking the standing position.
      MATERIALS AND METHODS: Fifty consecutive patients (28 males and 22 females), with
      both chronic low pack pain and recurrent painful blockages, were selected and
      studied using a 1.5 T Gyroscan Intera Philips MRI unit (Philips, Best, Holland)
      and a dedicated axial loading apparatus (MIKAI manufacturing, Genoa, Italy).
      RESULTS: After loading, no significant modifications occurred in ten patients
      (20%), a spinal stenosis was seen in 18 patients (45%), an increase in the discal
      protrusions or hernias was detected in 8 patients (20%) and a significant
      accentuation of the spondylolisthesis was observed in 6 patients (15%).
      CONCLUSION: Axial loading MRI provides valuable information for specific non
      invasive or operative management of low back pain.

PMID- 14598604
TI  - Mycoplasma pneumoniae infection and its genotypical characterization in children
      of Hokkaido, Japan.
AB  - To investigate the etiology of Mycoplasma pneumoniae infections we conducted a
      prospective study covering the total pediatric population in Hokkaido, Japan.
      Paired sera for serologic assays were available for more than half of the cases
      (n = 921; 398 as pneumonia and 523 as bronchitis). The nasopharyngeal swabs were
      also collected for isolation and PCR study. The types of P1 gene from clinical
      isolates of M. pneumoniae obtained from two different areas of Hokkaido, Sapporo
      and Kushiro, were determined by PCR-RFLP assay. M. pneumoniae was identified in
      174 (43.7%) out of 398 patients with pneumonia and was identified in 78 (14.9%)
      out of 523 (86.2%) patients with bronchitis. P1 genes of 14 clinical isolates of
      M. pneumoniae were classified into 13 group II and 1 group I. Two clinical
      isolates were unclassified by PCR-RFLP assay. Mycoplasma infections were seen
      even in patients less than 5 years of age. Generation of antigenic variation by
      DNA recombination may occur in clinical isolates.

PMID- 14598605
TI  - Parathyroid hormone-related peptide and cardiovascular system.
AB  - The parathyroid hormone-related peptide (PTHrP) was initially identified in the
      early eighties, as the humoral mediator causing hypercalcaemia associated with
      malignancy. However, recently PTHrP was also shown to mediate a wide range of
      local paracrine/autocrine and intracrine functions in various tissues under
      physiological and pathological conditions. Indeed, PTHrP is a polyhormone, which
      can act through different receptors, including the type 1 parathyroid hormone
      (PTH) receptor 1 (PTH-1R). In the cardiovascular system, PTHrP appears to have
      potent effects on vascular smooth muscle cells and cardiomyocytes, where it
      participates in different pathological conditions, such as ischemia and heart
      failure. Therefore, it is conceivable that further studies on the regulation of
      PTHrP expression, characterization of its autocrine/paracrine/intracrine
      functions and definition of its intracellular signal transduction pathways in
      cardiomyocytes and cardiac vascular smooth muscle cells can elucidate the
      potential role of PTHrP in cardiovascular pathophysiology.

PMID- 14598606
TI  - Measurement of micronuclei by cytokinesis-block method in human, cattle, goat,
      pig, rabbit, chicken and fish peripheral blood lymphocytes irradiated in vitro
      with gamma radiation.
AB  - The frequencies of gamma-ray-induced micronuclei (MN) in cytokinesis-blocked (CB)
      lymphocytes at several doses were measured in three donors of seven species
      (human, cattle, goat, pig, rabbit, chicken, fish). Measurements performed after
      irradiation showed a dose-related increases in MN frequency in each of the donors
      of human, cattle, goat, pig and rabbit. The relative sensitivity of cattle, goat,
      pig and rabbit in peripheral blood lymphocytes (PBLs) compared with human PBLs
      was estimated by best fitting linear-quadratic model based on the radiation
      induced MN data over the range from 0 cGy to 400 cGy. In the case of MN frequency
      with 0.2, the relative sensitivities of cattle, goat, pig and rabbit PBLs were
      0.86, 0.98, 0.41 and 0.39, respectively. These data indicate that the induction
      of MN in CB cells following irradiation is similar in human, cattle and goat
      PBLs, while PBLs from pig and rabbit were much less sensitive to the MN induction
      effects of gamma-radiation than those from human. The micronucleus counts failed
      to show any evidence of radiation damage in the cells from chicken and fish.
      Measurements performed after irradiation showed a dose-related decrease in the
      formation of binucleated cells. We concluded that the use of CB cell from fish
      and chicken for detecting the results of radiation exposure was highly
      questionable. Our in vitro radiobiological study confirmed that the cytogenetic
      response obtained in blood from selected breeds of mammalian species can be
      utilized for application in environmental studies.

PMID- 14598607
TI  - Genotoxicity of nimesulide in murine bone marrow cells.
AB  - The genotoxic potentiality of nimesulide was evaluated in vivo in murine bone
      marrow cells. The human equivalent prophylactic dose of nimesulide (5 mg/kg body
      wt/day) was given to animals orally, once daily for seven consecutive days.
      Metaphase chromosome analyses revealed the significant increase in the incidence
      of chromosomal aberrations with preference to structural over the numerical ones.
      It therefore suggested the clastogenic effect of the nimesulide. The molecular
      mechanism of mutagenesis is yet to be determined.

PMID- 14598609
TI  - The auricular VX2 carcinoma--an animal model for sentinel node concept.
AB  - BACKGROUND: Considering the increasing clinical significance of the sentinel node
      (SN) concept, the applicability of the auricular VX2 carcinoma as an animal model
      for simulation of the SN concept was evaluated. MATERIALS AND METHODS: By means
      of blue dye and immunofluorescence-marked colloids, the lymphatic drainage of the
      auricle was described in 8 New Zealand white (NZW) rabbits. In 28 NZW rabbits,
      the extent of metastatic spread of auricular VX2 carcinomas after 8, 18, 21, 28
      and 32 days of tumor growth was examined. RESULTS: Lymphogenic metastatic spread
      was limited to the parotideal lymph node functioning as SN for 21 days. The
      disintegration of the physiologic integrity of the SN leads to metastatic spread
      in the area of the secondary lymph node station after 28 days of tumor growth
      with successive hematogenic spreading. CONCLUSION: The auricular VX2 carcinoma in
      NZW rabbits is an appropriate animal model for simulation of the lymphogenic
      metastatic spread and the SN concept in HNSCC.

PMID- 14598608
TI  - Effects of (-)-menthol on the distribution and metabolism of 2-aminofluorene in
      various tissues of Sprague-Dawley rats.
AB  - The purpose of the present study was to examine whether or not (-)-Menthol
      affects the distribution and metabolism of 2-aminofluorene (AF) in Sprague-Dawley
      rats. The AF, acetylated AF and AF metabolites were determined by using high
      performance liquid chromatography. AF was administered orally alone, with (-)
      Menthol at the same time, and after 24-hour (-)-Menthol pretreatment and then
      urine, stool, blood and tissues from liver, kidneys, stomach, colon and bladder
      were collected and assayed for AF and its metabolites. Compared to the control
      group, (-)-Menthol caused an increase of the metabolites excreted in the urine
      and stool. The major metabolite excreted both in the urine and in the stool was 9
      OH-AAF. The liver was the major metabolism center and the major residual
      metabolite of AF in the liver was 9-OH-AAF. When AF was given for 24 hours with (
      )-Menthol to SD rats, the rate of carcinogen acetylation is decreased in bladder,
      blood, colon, kidney and liver tissues.

PMID- 14598610
TI  - Effect of U-74389G (21-lazaroid) on intestinal recovery after acute mesenteric
      ischemia and reperfusion in rats.
AB  - Although it has been demonstrated that lazaroids can protect various organs from
      ischemia reperfusion injury, results obtained in the small intestine have been
      conflicting. On the other hand, it is not known whether inhibition of lipid
      peroxidation prevents intestinal ishemia-reperfusion injury. We investigated
      whether the administration of the aminolazaroid U-74389G had a beneficial effect
      on the repair process of the intestinal mucosa after transient mesenteric
      ischemia in a randomized-blind trial. Six groups of rats were subjected to a
      model of 60 min of intestinal ischemia that was produced by occluding the
      superior mesenteric artery. At the end of ischemia, U-74389G was administered
      intravenously and the clamp was removed to allow reperfusion. At 60 min after
      reperfusion animals were sacrificed and a 10-cm section of terminal ileum was
      resected. Its efficacy was evaluated by histopathological assessment, measurement
      of polymorphonuclear leukocytes and the extent of lipid peroxidation by measuring
      the small intestine tissue malondialdehyde. After 1 h of reperfusion, mucosal
      damage in both U-74389G-treated rats and control group rats was similar. However,
      the number of polymorphonuclear leukocytes in the intestinal mucosa was lower in
      the U-74389G group. Of particular interest was that U-74389G resulted in a
      statistically significant reduction in the concentration of small intestine
      tissue malondialdehyde, compared to the controls. When administered in an
      imitated clinical setting, U-74389G did not prevent intestinal ischemia
      reperfusion injury, however it protected the rat small intestine from oxidative
      damage by inhibiting lipid peroxidation.

PMID- 14598611
TI  - Immunohistochemical study of apoptosis-related Bcl-2 protein and its correlation
      with proliferation indices (Ki67, PCNA), tumor suppressor genes (p53, pRb), the
      oncogene c-erbB-2, sex steroid hormone receptors and other clinicopathological
      features, in normal, hyperplastic and neoplastic endometrium.
AB  - The bcl-2 gene codes for a protein which functions to inhibit apoptotic cell
      death, that involves an intrinsic normal cell death program. Bcl-2 overexpression
      was originally described in a follicular lymphoma, but more recently bcl-2
      expression has been observed in a variety of other human neoplasms. Variation in
      the frequency of apoptosis in hormone-sensitive tissues, such as the endometrium,
      is known to occur as a result of hormonal changes in both physiological and
      pathological circumstances. In this study we examined bcl-2 protein expression in
      a total of 170 samples of endometrial tissues (18 proliferative endometrium, 14
      secretory endometrium, 35 adenomatous hyperplasia and 103 carcinomas). The
      results were compared with p53, pRb and c-erbB-2 proteins expression, estrogen
      and progesterone receptors status, with the proliferative activity and with
      clinicopathological features. The expression of bcl-2 protein was lower in the
      group of carcinomas, when compared with the cases of adenomatous hyperplasia (p <
      0.0001), normal proliferative (p < 0.0001) and secretory endometrium (p = 0.07).
      In normal proliferative endometrium bcl-2 expression was correlated with PCNA (p
      = 0.026) and in secretory endometrium it was correlated with ER status (p =
      0.042). In hyperplasias, bcl-2 was correlated with PCNA (p = 0.019) and the PR (p
      = 0.007) expression. In carcinomas, decreased bcl-2 expression was associated
      with increased tumor grade (p = 0.04). A positive relationship between bcl-2
      expression and pRb, as well as PCNA score (p = 0.014 and p = 0.001,
      respectively), was also found. These results indicate that bcl-2 expression may
      play a role in the inhibition of apoptosis in endometrial carcinoma and its
      expression seems to be associated with tumor differentiation and cell
      proliferation.

PMID- 14598612
TI  - Glutathione-S-transferase pi expression and activity is increased in colonic
      neoplasia.
AB  - Glutathione-S-transferase (GST) isoenzymes are involved in the conjugation of
      glutathione to electrophilic carcinogens. Recent studies have shown increased
      levels and activities of GST in different tumors suggesting their role in
      carcinogen detoxification. This study compared GST activity levels and GST-pi
      protein expression in paired samples of colorectal cancer, adenoma and adjacent
      normal mucosa from a total of thirteen patients. GST was isolated from human
      colorectal specimens and assayed spectrophotometrically; Western immunoblot
      analysis was used to quantify GST-pi levels. GST activity was greater in both
      colorectal cancer and adenomas than in adjacent normal colonic tissue, although
      statistical significance was achieved only when comparing colorectal cancer to
      normal tissue. Based on these observations, we conclude that increased GST
      activity may be a useful marker of colonic neoplasia.

PMID- 14598613
TI  - Prognostic significance of hemoglobin concentration in nasopharyngeal carcinoma:
      does treatment-induced anemia have negative effect?
AB  - PURPOSE: To assess the value of hemoglobin concentration (HC) in predicting
      treatment outcomes in nasopharyngeal carcinoma (NPC) patients treated with
      chemotherapy (CT) and radiotherapy (RT). PATIENTS AND METHODS: Ninety-eight NPC
      patients treated with three courses of platinum-based neoadjuvant CT (NCT) and
      conventional RT were grouped as having normal HC (> or = 12.0 g/dl in females and
      > or = 13 g/dl in males), having mild anemia (MA) (13.0 g/dl > Hb > or = 11 g/dl
      in males, 12.0 g/dl > Hb > or = 11 g/dl in females) and having severe anemia (SA)
      (Hb < 11 g/dl). Massive decrease in HC (MDHC) was defined as > or = 1.5 g/dl
      decline with NCT. Along with other known risk factors (sex, age, histopathology,
      T stage, N stage, bilateral neck involvement, cranial nerve involvement and total
      RT time), the prognostic value of SA and MDHC were evaluated by Cox-regression.
      RESULTS: SA increased from 7 to 33% with NCT (p < 0.0001). Patients with SA had
      lower 5-year locoregional control (LRC) (49 vs. 73%, p = 0.03), disease-free
      survival (DFS) (42 vs. 68%, p = 0.01) and overall survival (OS) (43 vs. 69%, p =
      0.01) rates than patients with normal HC or MA. The presence of MDHC worsened 5
      year LRC (p = 0.002), DFS (p = 0.001) and OS (p = 0.02) rates. In multivariate
      analyses, MDHC and SA had pronounced effect on LRC and survival, respectively.
      CONCLUSION: MDHC and SA adversely affect treatment outcome in NPC patients
      treated with CT and RT. This may favour concomitant scheduling of RT and CT over
      neoadjuvant setting. Correction of HC before RT can improve the efficacy of RT
      and should be further evaluated.

PMID- 14598614
TI  - Skeletal growth factor involvement in the regulation of fracture healing process.
AB  - Skeletal growth factors are peptides that serve as signalling agents for living
      cells, thereby participating in the autocrine, paracrine, intracrine and
      endocrine bioregulation of tissues and organs in human physiology. Growth factors
      elicit their cellular actions after binding to specific receptors, which are
      large transmembrane proteins located on target cells. These receptors relay
      signals via specific intracellular signal transduction pathways capable of
      regulating gene transcription, thereby modifying cell proliferation, cell
      function, cell differentiation and apoptosis. Notably, growth factors and their
      specific receptors are expressed in and around a bone fracture repair site,
      suggesting strongly that they play a significant role in the physio/pathology of
      fracture healing. Conceivably, fine adjustments of specific growth factor
      activity during the different stages of the fracture healing process can serve as
      potential therapeutic targets, enhancing bone repair capacity and reducing
      irregularities of the healing process.

PMID- 14598615
TI  - Fatal outcome in a patient with metastatic prostate cancer and acquired severe
      hypogammaglobulinemia with complete absence of mature peripheral blood B-cells.
AB  - Common variable immunodeficiency (CVID) is the second most common
      immunodeficiency and may be classified according to the presence or absence of
      mature B-cells, the latter subgroup being exceedingly rare. We describe a 66-year
      old patient who over six months developed profound hypogammaglobulinemia
      associated with a complete absence of circulating B-lymphocytes and had a fatal
      outcome. Immunophenotypic analysis of a bone marrow aspirate demonstrated a
      strongly reduced number of B-cell precursors (CD34+/CD19+) but normal numbers of
      CD34+/CD45+ hematopoietic progenitor cells. This case is remarkable with respect
      to its documented rapid evolution. Possible triggers are discussed, a combination
      of drug toxicities being the most likely.

PMID- 14598616
TI  - Structural requirements of hydroxylated coumarins for in vitro anti-Helicobacter
      pylori activity.
AB  - We have previously found that a 7-hydroxycoumarin derivative has potent anti
      Helicobacter pylori (H. pylori) activity, comparable with metronidazole. In this
      report, we describe the structural requirement for the anti-H. pylori activity of
      several hydroxylated coumarins (1-23). It was found that 7-hydroxy-4
      methylcoumarin (6), 6,7-dihydroxy-4-methylcoumarin (8), 6-hydroxy-7-methoxy-4
      methylcoumarin (10) and 5,7-dihydroxycyclopentanocoumarin (21) showed comparable
      anti-H. pylori activity with metronidazole. The presence of 7- and/or 6-hydroxyl
      groups seems to be essential to display higher anti-H. pylori activity. Their
      activities depended on the number and position of the hydroxyl group on the
      benzenoid ring of the coumarin system. Methylation of the hydroxy group generally
      diminished the activity. In hydroxylated coumarins, the methyl group at C-4
      position enhanced the activity. The inhibitory activity of coumarins (1-23)
      against jack bean urease was examined, but no coumarins showed any inhibition at
      160 micrograms/mL.

PMID- 14598617
TI  - Colloids versus crystalloids as priming solutions for cardiopulmonary bypass: a
      meta-analysis of prospective, randomised clinical trials.
AB  - Using Cochrane methodology a review was performed of prospective randomized
      clinical trials comparing colloidal pump priming solutions for cardiopulmonary
      bypass. Dextrans were not considered. Database searches from 1966 through
      December 2002 delivered 265 articles. Seventeen studies finally met the
      eligibility criteria involving 997 patients. Summary odds ratio estimates from
      the 5 studies reporting mortality were 1.46 (n = 326; 95%-Confidence-Interval:
      .55 to 3.85; p = .49) for crystalloids against colloids and .74 (n = 150; 95%
      Confidence-Interval: .17 to 3.36; p = .49) for albumin versus synthetic colloids.
      Most commonly used outcome measures further included postoperative blood loss,
      platelet-count, fluid-balance and, colloid osmotic pressures from which
      Standardized Mean Differences (SMD) and their 95%-Confidence-Interval (95%CI)
      were extracted. Colloids produced significantly higher oncotic pressures and less
      positive fluid-balances. Although across 9 studies postoperative bleeding between
      colloids and crystalloids did not differ (n = 663; SMD: -.03, 95%CI: -.18 to .12;
      p = .69), platelet counts significantly favoured crystalloids (n = 465; SMD: 
      .42; 95%CI: -.68 to -.16; p = .00). However, compared to albumin platelet counts
      were significantly disfavoured only by starches (n = 321; SMD: -.55; 95%CI: -.77
      to -.32; p = .00). To conclude, using mere crystalloids produced more pronounced
      positive fluid balances and their avoidance as a single pump-prime component can
      be suggested. Since albumin is not necessarily associated with better outcomes
      and is more expensive, it is hard to continue its use. However, there is still
      insufficient evidence available to allow definitive conclusions.

PMID- 14598618
TI  - Comparison of remifentanil versus ketamine for paediatric day case adenoidectomy.
AB  - Few studies exist of using remifentanil and intravenous ketamine for anaesthetic
      induction in paediatric day case anaesthesia. Therefore, we studied 75
      unpremedicated ASA I-II children (age 1-7 years) who were randomly assigned in a
      double-blind fashion to receive either remifentanil (1 microgram/kg), ketamine
      (0.7 mg/kg) or placebo before the anaesthetic induction. Anaesthesia was induced
      with propofol and maintained with O2-N2O-sevoflurane. Induction characteristics,
      recovery times and the need for postoperative analgesia were evaluated. The
      required induction dose of propofol was lower in the groups receiving
      remifentanil and ketamine compared with the group receiving placebo. After
      tracheal intubation heart rate and blood pressure were better attenuated with
      remifentanil than with ketamine or placebo. In the recovery room children in the
      placebo group required more doses of oxycodone than the other two groups but this
      did not reach statistical significance. There were no differences between the
      groups in achieving predetermined recovery end-points, attaining full points on
      the Steward score or in the well being at home. In conclusion, remifentanil
      provides haemodynamically more stable induction of anaesthesia compared with
      ketamine or placebo. Ketamine with its' longer duration of action does not
      prolong recovery but does not have a clear opioid-sparing effect either in the
      immediate postoperative period.

PMID- 14598619
TI  - The effect of mandibular nerve block on opioid consumption, nausea and vomiting
      in bilateral mandibular osteotomies.
AB  - The purpose of this study was to compare the efficacy of a mandibular nerve block
      to placebo, in patients undergoing mandibular osteotomy surgery, regarding opioid
      consumption and adverse opioid induced side effects. Forty healthy individuals
      with a mean age of 19.7 years participated in the study. All subjects received
      lidocain 2% + adrenaline 1/80,000 versus placebo for mandibular nerve block in a
      randomized double-blind manner. Opioid consumption and opioid related side effect
      such as postoperative nausea and vomiting (PONV), and respiratory depression were
      assessed. RESULTS: The placebo group received significantly more sufentanil
      during the surgical procedure than the lidocaingroup. There were no significant
      differences in adverse opioid induced side effects. In the postoperative phase
      there was no difference in additional pain intervention between the two groups.
      CONCLUSION: The mandibular block during mandibular osteotomy reduces intra
      operative opioid consumption but does not alternate the opioid related side
      effects in the postoperative phase.

PMID- 14598620
TI  - Transdermal clonidine: does it affect pain after abdominal hysterectomy?
AB  - Clonidine has analgesic properties. We evaluated the analgesic effect of
      clonidine perioperatively. Forty patients undergoing abdominal hysterectomy
      received randomly the evening before surgery transdermal clonidine covered with
      overlay (CLO group) or the overlay alone (CTL group). Ten min before induction
      they received i.v. clonidine 1 microgram.kg-1 (CLO) or normal saline (CTL).
      Induction was accomplished with fentanyl 5 micrograms.kg-1, thiopentone 5 mg.kg
      1, cis-atracurium 0.15 mg.kg-1 and maintenance with sevoflurane 2% in 70% N2O.
      Hemodynamic parameters were recorded intraoperatively. Pain was assessed by VAS
      at rest and movement 2, 4, 6, 8, 24, 48, 72 h and 30 days, postoperatively.
      During the first 8 h postoperatively all patients received controlled analgesia
      with fentanyl followed by morphine i.m. 0.15 mg.kg-1 and paracetamol. From 24-72
      h postoperatively, patients received 75 mg propoxyphene and 600 mg paracetamol
      i.m., on demand. Arterial blood pressure was lower in the CLO group 0, 3, 10 min
      after intubation. There was no difference in pain or fentanyl consumption 8 h
      postoperatively. The CLO group required less analgesics 24 h postoperatively (p =
      0.023). The two groups did not differ in pain or analgesic requirements 72 h and
      30 days postoperatively. Clonidine had a weak opioid sparing effect 24 h post
      operatively, but did not affect pain in long term.

PMID- 14598621
TI  - Barotrauma-induced tension pneumoperitoneum.
AB  - We report the case of a massive tension-pneumoperitoneum developing immediately
      after starting mechanical ventilation (barotrauma). Careful analysis of CT-data
      provided meaningful informations in assessing the non surgical pulmonary source
      of pneumo peritoneum.

PMID- 14598622
TI  - Acute epiglottitis in children: a review following an atypical case.

PMID- 14598623
TI  - The cognitive functions of language.
AB  - This paper explores a variety of different versions of the thesis that natural
      language is involved in human thinking. It distinguishes amongst strong and weak
      forms of this thesis, dismissing some as implausibly strong and others as
      uninterestingly weak. Strong forms dismissed include the view that language is
      conceptually necessary for thought (endorsed by many philosophers) and the view
      that language is de facto the medium of all human conceptual thinking (endorsed
      by many philosophers and social scientists). Weak forms include the view that
      language is necessary for the acquisition of many human concepts and the view
      that language can serve to scaffold human thought processes. The paper also
      discusses the thesis that language may be the medium of conscious propositional
      thinking, but argues that this cannot be its most fundamental cognitive role. The
      idea is then proposed that natural language is the medium for nondomain-specific
      thinking, serving to integrate the outputs of a variety of domain-specific
      conceptual faculties (or central-cognitive "quasimodules"). Recent experimental
      evidence in support of this idea is reviewed and the implications of the idea are
      discussed, especially for our conception of the architecture of human cognition.
      Finally, some further kinds of evidence which might serve to corroborate or
      refute the hypothesis are mentioned. The overall goal of the paper is to review a
      wide variety of accounts of the cognitive function of natural language,
      integrating a number of different kinds of evidence and theoretical consideration
      in order to propose and elaborate the most plausible candidate.

PMID- 14598624
TI  - Are developmental disorders like cases of adult brain damage? Implications from
      connectionist modelling.
AB  - It is often assumed that similar domain-specific behavioural impairments found in
      cases of adult brain damage and developmental disorders correspond to similar
      underlying causes, and can serve as convergent evidence for the modular structure
      of the normal adult cognitive system. We argue that this correspondence is
      contingent on an unsupported assumption that atypical development can produce
      selective deficits while the rest of the system develops normally (Residual
      Normality), and that this assumption tends to bias data collection in the field.
      Based on a review of connectionist models of acquired and developmental disorders
      in the domains of reading and past tense, as well as on new simulations, we
      explore the computational viability of Residual Normality and the potential role
      of development in producing behavioural deficits. Simulations demonstrate that
      damage to a developmental model can produce very different effects depending on
      whether it occurs prior to or following the training process. Because
      developmental disorders typically involve damage prior to learning, we conclude
      that the developmental process is a key component of the explanation of endstate
      impairments in such disorders. Further simulations demonstrate that in simple
      connectionist learning systems, the assumption of Residual Normality is
      undermined by processes of compensation or alteration elsewhere in the system. We
      outline the precise computational conditions required for Residual Normality to
      hold in development, and suggest that in many cases it is an unlikely hypothesis.
      We conclude that in developmental disorders, inferences from behavioural deficits
      to underlying structure crucially depend on developmental conditions, and that
      the process of ontogenetic development cannot be ignored in constructing models
      of developmental disorders.

PMID- 14598625
TI  - Cross-industry benchmarking: is it applicable to the operating room?
AB  - The use of benchmarking has been growing in nonmedical industries. This concept
      is being increasingly applied to medicine as the industry strives to improve
      quality and improve financial performance. Benchmarks can be either internal (set
      by the institution) or external (use other's performance as a goal). In some
      industries, benchmarking has crossed industry lines to identify breakthroughs in
      thinking. In this article, we examine whether the airline industry can be used as
      a source of external process benchmarking for the operating room.

PMID- 14598626
TI  - Early Start: an obstetric clinic-based, perinatal substance abuse intervention
      program.
AB  - Maternal substance abuse is a serious problem with significant adverse effects to
      mothers, fetuses, and children. The Early Start Program provides pregnant women
      in a managed care organization with screening and early identification of
      substance abuse problems, early intervention, ongoing counseling, and case
      management by a licensed clinical social worker located in the prenatal clinic,
      where she is an integral part of the prenatal team. We describe the development
      of the Early Start Program, its administrative history, and how it has interfaced
      with clinicians and administrators. We also highlight two important program
      characteristics: the partnership with a perinatal health services research unit
      and the degree to which the program could be "exported" to other managed care
      settings.

PMID- 14598628
TI  - A time for change: for the road to excellence for health care professionals.
AB  - This article addresses the changes affecting all of health care. Change should
      first be driven by data--data are what will be used to make clinical and business
      decisions that will result in better quality care. Employees should be held
      accountable for results, and celebrations should be provided for these changes.
      Customers have needs and goals that must be met, and if we do not meet the needs,
      our competition will. Management must understand the principles of quality and
      must encourage growth in employees. To bring change to your health care
      organization, you must embrace and encourage change.

PMID- 14598627
TI  - Managing Alzheimer's disease in primary care in Crete, Greece: room for
      improvement.
AB  - As Greece moves during the last two decades toward a national health care system,
      which gives emphasis to the development of a primary care system, many worry how
      to ensure that the quality of care is assessed. This is more apparent in the
      rural populations, in which health care is served to a large extent by physicians
      without formal training in general practice. This article explores the level of
      knowledge of primary care physicians in relation to Alzheimer's disease in
      geographically defined areas of Crete, Greece, in comparison with that of general
      practitioners in Ostergotland, Sweden, and in Iceland. It emphasizes the need for
      better education and training for primary care physicians in Crete in both the
      early diagnosis and management of Alzheimer's disease.

PMID- 14598629
TI  - Interview with Michael S. Jacobs, JD.

PMID- 14598630
TI  - Leprosy in China.
AB  - Leprosy has definitely been present in China for at least 2,000 years. Through
      painstaking efforts over the past half century, China has put leprosy under
      control and reached the WHO's target at elimination of leprosy at the national
      and subnational level. But difficulties as well as problems like disabilities,
      discrimination, drug-resistance and dismissing of research still remain in the
      control of leprosy. Highly attention should be continuously paid on to attain the
      prevalence rate of less than 0.1/10,000 and the incidence rate below 0.5/100,000
      in all counties (cities) throughout the country by the year 2010.

PMID- 14598631
TI  - [The history of Yunosawa village and the policy of leprosy of Japan III].
AB  - There was a village which was called Yunosawa, lots of leprosy patients lived,
      existed from 1887 to 1941, Kusatu town, Gunnma Prefecture, Japan. It was the only
      place continued securing self-government to the last as area was free from the
      isolation policy of State in prewar days there. The aim of this study will make
      clear the dynamism of "The protection from the tension of the society of leprosy
      patient currently persecuted" to "The defense of the society from the leprosy
      patient who is a source of infection". In this study, explained the history of
      the Yunosawa village and the shift of the policy of leprosy by State had relation
      to the village. In addition, showed worth of free medical-treatment area here.

PMID- 14598632
TI  - [Consequences of leprosy in the skin].
AB  - This summarizes a variety of impairments found in healed leprosy patients.
      Visible impairments and some secondary complications are presented from the
      viewpoint of dermatology. Neural damage may bring neuralgia, paraesthesia and
      progressive neuropathy after healing of leprosy itself.

PMID- 14598633
TI  - [What was found in deformities of leprosy patients from the view-point of
      orthopedics?].
AB  - No more deformities which are the cause of social stigma by early detection and
      chemotherapy! Let patients learn how to avoid getting deformed to keep normal ADL
      & QOL. Fight against the nerve damage and stop the progressive deformities by
      organizing the team approach. Instead of intense efforts of taking care by well
      organized team work, deformities are resulted inevitably in some cases. Let their
      deformities be out of the way of their keeping normal community lives without any
      prejudice, respecting their human rights and dignity.

PMID- 14598634
TI  - [The sequelae of Hansen's disease. (Pathologic viewpoint of etiologies,
      morphologies and countermeasures)].
AB  - The proportion of glomerulonephritis, often a sequence of arteriolitis, among the
      sequelae of Hansen's disease after the introduction of chemotherapy increased
      markedly in Japan and nullified that of once prevalent tuberculosis after 1960s.
      However, most significant aftermath of the disease for numbers of years in the
      past have been peripheral nerve injuries worldwide for which effective
      countermeasures are yet to be developed. In this brief autopsy cases study from
      1960s to 1990s, we confirmed the presence of cases in which arteriolitis and
      resulted infarction of peripheral nerves and not M. leprae itself were shown to
      be the major cause of axonal damages. There were also cases in which the
      accumulation of the bacilli without vascular changes did not damage the axons.
      The cases as these could not be solitary but should be rather common in this time
      of chemotherapy. If so, the methods to reconstruct nerves and blood vessels by
      promoting those regeneration should be developed to cope with the situation for
      surgeon, assisted by pathologists.

PMID- 14598635
TI  - [A case of Hansen's disease seen in an Indonesian resident, and tracing of the
      patient after coming back to Indonesia].
AB  - A 26-year-old Indonesian male living in Japan consulted our hospital with
      complaint of fever, general malaise and infiltrative erythematous plaques
      associated with lymph node swelling. Physical examination revealed a sensation
      disorder in the distal portion of the extremities and hypertrophy of peripheral
      nerves. Histopathology of the skin lesion showed the multifocal granulomatous
      inflammation containing many acid-fast bacilli associated with infiltration of
      foam cells and neutrophils. Under the diagnosis of leprosy (LL type) accompanied
      by erythema nodosum leprosum, the combined chemotherapy (clofazimine, rifampicin,
      and diphenyl sulfone) was started. For the leprosy reaction, short-term
      administration of the systemic steroid was added. The general condition was
      carried out soon, and the sensation disorder has also been gradually improved.
      The patient came back to Indonesia after 6 months treatment because of the time
      limit of visa. We traced the patient's condition through personal networks, and
      knew that the patient could not have continual treatment for the disease, and
      that he is suffering from disability of hands and feet. In this case, several
      medical facilities were consulted before the final diagnosis of leprosy. The
      Japanese medical doctors should also remember this disease when they examine
      persons with infiltrative skin eruptions and sensation disorders.

PMID- 14598636
TI  - [A case of paucibacillary leprosy].
AB  - We report a case of leprosy. A 31-old-phillippine female present with 5 month
      history of an erythematous plaqe on her right neck. Examination showed 4
      erythematous plaques with her. A histological examination of the skin lesion of
      hir thigh revealed granulomas around nerve and skin appendages which consist of
      lymphocytes, epidermoid cells and giant cells. Although no acid fast bacilli were
      not demonstrated by skin biopsy with Ziehl-Neelsen staining, the Mycobacterium
      leprae-specific DNA was detected by polymerase chain reaction method. A diagnosis
      of paucibacillary leprosy had made. We started treatment with ofloxacin but she
      return to philippine soon.

PMID- 14598637
TI  - [A case of lepromatous type Hansen's disease].
AB  - A 68 year-old male presented with painful swelling in the extremities and
      disseminated small brownish nodules over his entire body. A histological
      examination of the skin nodules showed multiple granuloma and a thickened
      peripheral nerve bundle surrounded with foamy macrophages and a few lymphocytes.
      Fite stain revealed numerous acid fast bacilli within the cytoplasm of the foamy
      cells. A diagnosis of lepromatous leprosy was thus made and multi-drug therapy
      following the Japanese guideline with DDS, rifampicin and clofazimine was
      started. The clinical features improved, and the morphological index decreased
      after undergoing chemotherapy. Although a severe type 1 reaction developed after
      four months of treatment, he was treated with oral prednisolone at a dose of 40
      mg/day.

PMID- 14598638
TI  - [Two cases of Hansen's disease].
AB  - We report two cases of Hansen's disease. Case 1 was 71-year old Japanese man who
      developed left ulnar nerve palsy since 7 years ago, multiple erythema on his body
      since 2-3 years ago, and erythematous nodules on his face since 3 months ago. He
      had no history of living outside Ibaraki prefecture. The clinical feature, the
      skin biopsy, laboratory data showed that he had borderline lepromatous leprosy.
      He was treated with multi-drug therapy which was effective and was stopped 3
      years after the bacterial index showed negative. Ten months later, erythema on
      his body and face appeared and the therapy was restarted. Case 2 was 68-year old
      Japanese man who developed 5 cm of nummular erythema with slight numbness on his
      right forearm since 3 months ago. He had lived in Brazil since he was 24 to 64
      years old. The skin biopsy showed epithelioid cell granuloma in the dermis
      involving vessels and nerves. Polymerase chain reaction test showed the M.leprae
      DNA, and he was diagnosed as indeterminate leprosy. He was treated with dapson
      and rifampicin and 2 months later, erythema and numbness disappeared.

PMID- 14598639
TI  - [A case of Hansen's disease].
AB  - With the abolition of Leprosy Prevention Act of 1996, that opportunities
      examining the Hansen's disease patient with a general medical institution
      increase is expected. Because we experienced Hansen's disease of a staying in
      Japan foreigner then in such time, we present it. A case is a man of 50 years
      old, who is a Filipino of 3 years living in Japan. It recognized infiltrating
      deep erythema in a face and trunk. Furthermore, in dysesthesia, nerve
      hyperplasia, and Bl is positive in skin smear. Histopathology is a typical
      finding. Than the above, we diagnosed it as Hansen's disease of BL-LL type.

PMID- 14598640
TI  - [A case of multibacillary leprosy].
AB  - We report a 74-year-old Japanese man who occurred leprosy at the age of 68. He
      moved to Bolivia at the age of 33 as an immigrant. He complained erythematous
      plaques on his trunk and extremeties and dysuria. Skin biopsy specimen revealed
      granulomatous lesions and acid fast staining showed numerous number of positively
      stained bacilli. He was diagnosed as multibacillary leprosy and MDT containing
      DDS, RFP, and CLF was started. During the treatment, he developed borderline
      reaction twice presenting severe pain and marked swelling on his hand and foot.
      The reaction was successfully treated with daily dose of 50 mg prednisolone
      combined with anti-leprosy drugs. SPFX, MINO, and CAM were not able to be used
      due to the side effects. One year has been passed after the stop of treatment
      without relapse.

PMID- 14598641
TI  - [Case report revisited: review of the 6 cases].
AB  - Out of the cases we experienced in our 11-year service in sanatorium, 6 cases
      were selected to review the medical care and social environment that each patient
      was involved. Two cases were the residents in a sanatorium and 4 cases were in
      the community, including 2 cases having foreign nationality. The review of these
      cases drew the following conclusions. 1. We must be aware of our responsibility
      for early diagnosis and treatment of leprosy to prevent tragic disability. 2. The
      fixed duration of MDT/MB may not be enough for LL cases having high bacterial
      load before treatment. Enough duration of chemotherapy and follow-up is desired
      to prevent avoidable disability. 3. Basically, the treatment of leprosy should be
      carried on in outpatient clinic. The duration of hospitalization, if necessary,
      should be shortest to enhance patient's motive for treatment. 4. Intermittent
      administration of RFP must be done under direct observation. 5. For foreign
      patients not accustomed to the life in Japan or elderly patient living by
      oneself, various supports from community are greatly helpful to achieve the long
      course of leprosy treatment. Through these supports, we can expect community
      enlightening that may promote rehabilitation of the people once suffered from
      leprosy.

PMID- 14598642
TI  - [A case suspected multibacillary leprosy].
AB  - The presence of acid-fast bacilli in the lesion and its positive culture usually
      provide the diagnosis in cutaneous mycobacteriosis. But in diagnosis of leprosy,
      characteristic clinico-histopathological findings are so important as the
      demonstration of the organism, because of the failure to grow Mycobacterium
      leprae in vitro. It is classified in various forms along a spectrum of infectious
      and immunological symptoms supported by the pathogen-host relationship. The
      patient was a Japanese woman 69 years of age. She had been diagnosed as
      multibacillary leprosy with the positive results of slit-smear tests and the
      confirmation of the genomic sequence by PCR. Multidrug therapy had been started,
      but it was discontinued afterwards because an exact diagnosis of leprosy could
      not be determined by clinical, histological, and immunological assessment. As its
      diminishing prevalence in Japan, where ordinary physicians cannot have
      opportunities to see leprosy patients and they are unfamiliar with protean
      manifestations of the disease, it can be very difficult to make accurate
      diagnosis in those cases with atypical findings.

PMID- 14598643
TI  - [Surgery for acoustic tumor].

PMID- 14598644
TI  - [Clinical manifestations of infantile moyamoya disease].
AB  - PURPOSE: The present study aimed to clarify clinical manifestations of infantile
      moyamoya disease by comparing them with those of schoolchild moyamoya disease.
      SUBJECTS AND METHODS: This study included a total of 55 patients who were
      diagnosed as moyamoya disease on cerebral angiography. Their medical records were
      precisely evaluated. CT or MRI was performed to examine the location of cerebral
      infarction in all subjects. Cerebral blood flow was measured in 33 patients
      before surgery, using the 133-xenon inhalation method and single photon emission
      computed tomography (SPECT). Postoperative full-scale IQ (FSIQ) was also
      examined. RESULTS: Of 55 patients, onset age was < 6 yr in 32 (infantile group)
      and > or = 6 yr in 23 (schoolchild group). Completed stroke was significantly
      more frequent in the infantile group than in schoolchild group (p = 0.0014).
      Incidence of cerebral infarct was also higher in the infantile group than in the
      schoolchild group (p = 0.0023). PCA stenosis/occlusion was observed in 14 of 32
      infantile patients, but only in 4 of 23 schoolchild patients (p = 0.0474). Mean
      cerebral blood flow value was significantly lower than control value in the
      infantile group, but not in the schoolchild group. The effect of bypass surgery
      on cerebral ischemic attack was satisfactory in both groups. However, the
      postoperative FSIQ value was significantly lower in the infantile group than in
      the schoolchild group (p = 0.0452). CONCLUSIONS: The present study showed that
      infantile moyamoya disease involves a higher risk for cerebral infarct and
      completed stroke due to its more advanced stage, and that earlier diagnosis and
      treatment should be performed to improve the mental prognosis of patients.

PMID- 14598645
TI  - [Ion-beam irradiated ePTFE for an artificial dura mater].
AB  - Expanded polytetrafluoroethylene (ePTFE) is a stable polymer and widely used as a
      prosthesis because of its chemical inertness. However, ePTFE as an artificial
      dura mater is often associated with postoperative leakage of the cerebrospinal
      fluid (CSF) due to its very low adhesiveness to fibrin glue and surrounding
      tissue. The surfaces of ePTFE were modified by ion-beam irradiation in order to
      improve tissue adhesiveness. The morphological changes of ePTFE that was
      irradiated with 150 keV-He+, Net, Ar+ and Kr+ ions applied at a rate of 1 x
      10(14), 5 x 10(14) and 1 x 10(15) ions/cm2 were examined with scanning electron
      microscopy. Next, surrounding tissue reactions to the implanted ePTFE into the
      rabbit calvarial defects were analyzed at intervals from 1 week up to 1 month.
      The micromesh structures of the ePTFE were destroyed by ion-beam irradiation, and
      the depth and width of the gaps increased with heavy particle ion and irradiated
      fluence. In an implantation study using experimental rabbits, a dura defect was
      patched with four types of ion-beam irradiated ePTFE with different in
      irradiation fluence. A CSF leakage was observed in the rabbit covered with non
      irradiated ePTFE, but, CSF leakage did not occur in any of the rabbits covered
      with ion-beam irradiated ePTFE that adhered in a water-tight manner to
      surrounding tissues. Histological study indicated that fibroblast-like cells had
      infiltrated and anchored the gaps in the ion-beam irradiated ePTFE. Ar+ or Kr+
      with 1 x 10(15) ions/cm2 irradiated ePTFE had the highest adhesiveness and
      produced the best healing of dura defects.

PMID- 14598646
TI  - [Spontaneous extra-cranial vertebral artery dissection accompanied with multiple
      cerebral infarctions due to re-canalization].
AB  - In this paper we report a case of vertebral artery occlusion caused by
      spontaneous extra-cranial vertebral artery dissection accompanied with cerebellar
      and thalamic infarctions due to recanalization. Furthermore, after a nine-week
      time lapse we performed PTA/stenting. A 62-year-old man with vertigo, dysarthria
      and nuchal pain without injury was admitted to our hospital. Emergent cerebral
      angiography revealed an occlusion of the right vertebral artery and the right
      PICA. The patient's symptoms gradually improved owing to local-fibrinolysis with
      urokinase for the right PICA via the left vertebral artery. Follow-up angiography
      (2 weeks later) showed re-canalization and dissection of the right vertebral
      artery. Treatment for spontaneous extra-cranial vertebral artery dissection is
      chosen, depending on whether there is co-lateral circulation or not. We obtained
      a good result using PTA/Stenting in this case of spontaneous extra-cranial
      vertebral artery dissection within nine weeks after onset.

PMID- 14598647
TI  - [A case of ruptured aneurysm of the middle cerebral artery associated with dural
      arteriovenous fistula in the anterior cranial fossa].
AB  - A 66-year-old man suffered from subarachnoid hemorrhage due to the rupture of a
      right middle cerebral artery aneurysm that was detected by 3D-CTA. He underwent
      an emergent clipping operation. Incidentally, postoperative DSA demonstrated
      dural arteriovenous fistula in the left anterior cranial fossa, which was fed by
      the left anterior ethmoidal artery and drained into the superior sagittal sinus
      via the cortical vein of the left frontal lobe. We performed electrocoagulation
      and division of the fistula at the second surgery. Subsequently, he underwent a
      ventriculo-peritoneal shunt and was discharged without any neurological deficits.
      We reviewed reported cases of rare association of ruptured cerebral aneurysm and
      dural arteriovenous fistula in the left anterior cranial fossa.

PMID- 14598648
TI  - [Surgical reconstruction of the common carotid artery by an ePTFE graft for
      invasive thyroid cancer: a case report].
AB  - Surgical reconstruction of the carotid artery using a synthetic graft is rarely
      performed. A 71-year-old woman developed hoarseness and was diagnosed as having
      thyroid cancer. Computed tomography (CT) and angiography revealed an irregular
      thyroid tumor invading the left common carotid artery, and encasement of the
      artery by the tumor. Left common carotid angiography showed an irregularity of
      the common carotid artery wall and a dense tumor stain fed by the superior
      thyroid artery. Dissection of the thyroid cancer from the common carotid artery
      was judged to be impossible during surgery, so resection of the whole tumor
      together with the common carotid artery was carried out. The left common carotid
      artery was reconstructed using an expanded polytetrafluoroethylene (ePTFE) graft.
      No cerebral ischemia was evident after surgery. Postoperative CT and magnetic
      resonance angiography demonstrated patency of the carotid artery, and no tumor
      recurrence was confirmed at a 27-month follow up. The ePTFE graft appears to be a
      suitable synthetic graft for reconstruction of the carotid artery.

PMID- 14598649
TI  - [A case of embolic infarction originating from extracranial vertebral artery
      stenosis by cervical spondylosis at C5/6: its pathogenesis and surgical
      treatment].
AB  - We report a case of right brainstem and cerebellar infarction induced by head
      rotation. The infarction was due to an artery to artery embolism originating from
      extracranial vertebral artery stenosis resulting from C5-6 cervical spondylosis.
      A-64-year-old man with cervical spondylosis experienced swallowing difficulty and
      vertigo while eating dinner. Neurological examination at admission indicated
      lateral medullary syndrome (Wallenberg syndrome). MRI (FLAIR) revealed multiple
      high-intensity signal areas in the right lateral medulla and the cerebellar
      hemisphere in the territory of the posterior inferior cerebellar artery (PICA).
      Right vertebral angiogram demonstrated marked stenosis in the neutral position
      and occlusive changes with head rotation to the right (30 degrees) at C5-6.
      Rotation induced substantially delayed filling of the right vertebral artery. To
      remedy this, we resected the osteophyte, fused the uncovertebral joint and
      connective tissue adhering tightly to the right vertebral artery at C5-6 level,
      and unroofed the transverse foramens at C5 and C6. Post-operative angiogram
      confirmed the disappearance of marked stenosis and improved antegrade filling of
      the right vertebral artery. In the present report, the pathogenesis and surgical
      treatment of this particular case are discussed.

PMID- 14598650
TI  - [Cavernous arteriovenous fistula presenting myelopathy: a case report].
AB  - Intracranial dural arteriovenous fistula (DAVF) rarely presents with myelopathy.
      We discuss the diagnosis and treatment of this entity. A 76-year-old woman
      presented with tetraparesis and sphincter dysfunction. Magnetic resonance imaging
      demonstrated a high signal intensity from the medulla oblongata to the upper
      cervical cord on T2-weighted images. Angiograms showed a cavernous DAVF and
      venous drainage to perimedullary spinal veins via the petrosal vein. It was
      concluded that, myelopathy had resulted from congestion of the spinal veins.
      Transarterial embolization of the left cavernous sinus was performed through the
      left sphenopalatine artery with 25% NBCA after another feeding artery had been
      occluded using fiber coils. The patient's tetraparesis and sphincter dysfunction
      gradually improved after embolization, while the high signal intensity on T2
      weighted images disappeared within two months after treatment. We should take
      intracranial DAVF into consideration in patients with myelopathy of unknown
      origin.

PMID- 14598651
TI  - ["How I do it" no. 6, a case with a giant petroclival meningioma presented with
      progressive ataxia: how should this case be managed?].

PMID- 14598652
TI  - [Brain functional imaging by NIRS topography: basic knowledge of clinical nerve
      physiology for neurosurgeons].

PMID- 14598653
TI  - [Crosstalk between the immune and skeletal system].

PMID- 14598654
TI  - [Effects of therapies on childhood systemic lupus erythematosus].
AB  - We analyzed the effects of three therapies on 30 patients with childhood systemic
      lupus erythematosus, and classified the patients into three groups. The therapies
      were as follows; Group A (8 cases), methylpredni-solone (mPSL) pulses plus oral
      prednisolone (PSL) alone, Group B (10 cases), mPSL pulses plus oral PSL and
      mizoribine (MZB) or azathioprine (AZP), Group C (12 cases), mPSL pulses and
      intravenous cyclophosphamide (IVCY) pulse therapy plus oral PSL and MZB or AZP.
      Three years after treatment, we compared the laboratory data (C3, C4, CH50 and
      anti-DNA antibody), the SLEDAI scores and numbers of relapses in these three
      groups. We demonstrated that group C had the best data, and this data indicated
      that the median C3, C4 and CH50 increased and that the median anti-DNA antibody
      and the mean of the numbers of relapses decreased. In conclusion, the combination
      of immunosuppressants and IVCY appeared to offer great benefits in childhood
      systemic lupus erythematosus.

PMID- 14598655
TI  - [Alignment of lower extremity in rheumatoid arthritis patients with a history of
      both total hip replacement and total knee replacement].
AB  - OBJECTIVE: The following is a retrospective study on lower extremity alignment of
      rheumatoid arthritis (RA) patients with a history of both Total Hip Replacement
      (THR) and Total Knee Replacement (TKR). METHODS: From 1992 to 2000, our
      department had 26 rheumatoid arthritis patients who underwent both THR and TKR.
      We classified these patients into three groups based on radiographic alignment of
      the lower extremities in the standing position: Knock-knee (valgus deformity of
      the knees), Bowleg (varus deformity of the knees) and Windswept Deformity (one
      knee in severe varus alignment with the other in severe valgus alignment).
      Furthermore, we identified dominant weight bearing points of the hip as
      classified by the following new criteria: Central Shift, Lateral Shift, and
      Upward Shift. Mal-alignment was then evaluated based on these two classification
      systems. RESULTS: Of the 26 patients, 22 patients met our criteria and 4 did not.
      In mal-alignment, we had 11 cases in the knock-knee group, 5 cases in the bowleg
      group, and 6 cases in the Windswept deformity. Using the new criteria, central
      shift had 6 cases; lateral shift had 6 cases; and upward shift had 10 cases. The
      groups of Lateral shift and Central shift demonstrated deformities of the lower
      extremities were influenced by moving weight bearing points, pelvis obliquity,
      and adduction contractures of the hip joint. In upward shift, weight bearing
      lines did not change. Consequently, destruction of the joint in this group
      progressed symmetrically. Windswept deformity was asymmetric and had severe
      destruction on the other side of the knee and forefoot. DISCUSSION: Moving of
      weight bearing point, pelvis obliquity, and adduction contractures of the hip
      joint affected the severity of mal-alignment of the lower extremities.

PMID- 14598656
TI  - [Beneficial effect of high-dose etidronate on periarticular calcinosis associated
      with arterial and periarticular basic calcium phosphate (BCP) crystal deposition
      disease].
AB  - Basic calcium phosphate (BCP) deposition disease is a crystal-induced
      inflammation syndrome. We report a beneficial effect of high-dose etidronate, one
      of the bisphosphonates, on periarticular calcinosis in a case of arterial and
      periarticular BCP crystal deposition disease. A 55-year-old woman was referred to
      St. Marianna University Hospital because of a 30-year history of recurrent acute
      periarthritis. The X-ray photographs revealed periarticular calcinosis of the
      hand and foot, wrist, and knee joints without bony erosions and the calcification
      of carotid and popliteal arteries. The biopsied specimen from periarticular
      tissue showed Alizalin-red and von Kossa staining-positive crystals. With the
      diagnosis of BCP crystal-induced periarthritis, she has been treated with
      colchicine and probenecid. This regimen was partially effective in terms of a
      decrease in the frequency of periarthritic attack. Despite the treatment,
      periarticular calcinosis increased in size and number. She was treated with 800
      mg of etidronate 3 months after the etidronate therapy; periarticular calcinosis
      was diminished although arterial calcification was unchanged. This case suggests
      that high-dose etidronate might be useful for heterotopic calcification
      associated with rheumatic diseases.

PMID- 14598657
TI  - [Adult onset Still's disease (AOSD) treated with a combination of prednisolone,
      cyclosporin A, and methotrexate].
AB  - A 58-year-old Japanese woman developed spiking fever, polyarthralgia and
      hepatosplenomegaly, with highly elevated levels of c-creactive protein (CRP) and
      ferrtin, and elevated erythrocyte sedimentation rate (ESR). The AOSD was
      diagnosed according to the Yamaguchi-criteria of 1992. She was first treated with
      a combination of prednisolone (20 mg/day) and oral methotrexate (MTX) (7.5
      mg/week). This combination, however, was not effective with tapering the dose of
      prednisolone. When a high dose of cyclosporin A (CyA) (5.5 mg/kg/day) was then
      added to MTX (5 mg/week), the patient's fever and polyarthralgia decreased, and
      her elevated serological parameters such as CRP and ESR also gradually declined.
      Finally, the dose of prednisolone was tapered to 10 mg/day. Only a few cases of
      AOSD treated with CyA plus MTX have been reported. Thus, further careful
      observation will be needed to establish the usefulness of this drug combination
      as a therapy for AOSD.

PMID- 14598658
TI  - [A case of non-specific interstitial pneumonia in patient with microscopic
      polyangiitis].
AB  - Non-specific interstitial pneumonia developed as an initial manifestation in a
      patient with microscopic polyangiitis. A 62-year-old man was admitted to our
      hospital in March 2001, because of fever and intermittent myalgia of lower
      extremities. Chest X-ray had revealed reticular shadows in the bilateral middle
      and lower lung fields since 1996. Just before admission, the patient had been
      diagnosed as having nonspecific interstitial pneumonia (NSIP) from the specimen
      obtained by video-assisted thoracoscopic surgery (VATS) in another hospital.
      Physical examination on admission revealed bilateral episcleritis. Laboratory
      data showed elevated levels of CRP and KL-6, polyclonal gammaglobulinemia,
      positive rheumatoid factor and myeloperoxidase-antineutrophil cytoplasmic
      antibody (MPO-ANCA). Sensory and motor nerve conducting velocities were delayed
      in left peroneal nerve, but not other nerves, suggesting mononeuropathy. Biopsied
      specimens of the left quadriceps revealed vasculitis of arteioles. In spite of
      positive proteinuria and hematuria, no pathological lesion was found in the
      kidney. From all of these findings, the patient was diagnosed as having
      microscopic polyangiitis (MPA) without renal involvement. Methylprednisolone
      pulse therapy followed by intravenous cyclophosphamide pulse therapy improved his
      clinical conditions such as pyrexia, cough, myalgia, episcleritis and respiratory
      symptoms with decreased titer of serum MPO-ANCA. Thereafter, the dose of
      prednisolone was successfully tapered to 10 mg/day without clinical relapse. In
      the present patient who developed demonstrated non-specific interstitial
      pneumonia as an initial manifestation of MPA, VATS provided useful diagnostic and
      prognostic information, leading to an appropriate therapeutic choice.

PMID- 14598659
TI  - [Cyclophosphamide pulse therapy for pediatric systemic sclerosis].
AB  - We encountered three patients with pediatric systemic sclerosis. Patient 1 had
      systemic scleroderma, pigmentation and interstitial pneumonia at the age of 10
      years. Nine months after disease onset, she was treated with intravenous
      cyclophosphamide pulse therapy as induction therapy. After the initial treatment,
      the following clinical manifestations were dramatically improved: interstitial
      pneumonia, scleroderma and total skin score. Patient 2 was a 7-year-old girl, who
      complained of systemic scleroderma and pigmentation, and was found to have
      pulmonary hypertension. Six months after disease onset, she was administrated
      intravenous cyclophosphamide pulse therapy. Her scleroderma and total skin score
      were improved and the pulmonary hypertension did not deteriorate. Patient 3 was a
      15-year-old girl. Her initial treatment was vitamin E alone. She was admitted to
      our hospital two and half years after disease onset. Although she was given
      immunosuppressive therapy including cyclophosphamide, the severe condition of
      persisted, and she died after five months. It became possible for patient 1 and 2
      to achieve and maintain a marked improvement of the clinical manifestations as a
      result of cyclophosphamide pulse therapy early in the course of the disease. We
      further observed that their total skin score was decreasing while the clinical
      manifestations improved.

PMID- 14598660
TI  - [Systemic lupus erythematosus with steroid induced non-alcoholic steatohepatitis:
      a case report].
AB  - A 56-year old Japanese female was admitted to our hospital because of the
      increased levels of serum AST, ALT, and gamma-GTP. She was diagnosed with
      systemic lupus erythematosus in September, 1996 and had been on a regular
      glucocorticoid therapy since then. Abdominal ultrasonography showed the mild
      fatty liver, and hepatic histopathology revealed a typical and remarkable
      steatohepatitis, a remarkable neutrophil infiltration, and Mallory bodies.
      Because she had no history of alcohol-drinking, diagnosis of non-alcoholic
      steatohepatitis (NASH) was made. Treatment was started with a low-calorie diet,
      bed-rest, and an oral administration of alpha-tocopherol and bezafibrate with
      favorable effects on her serum levels of AST, ALT, gamma-GTP, and LDH. When a
      patient on a glucocorticoid therapy shows signs of fatty liver, diabetes
      mellitus, hyperlipidemia, an insulin resistance, NASH should be considered as one
      of the differential diagnosis. This is particularly important since proper
      therapy with a low-calorie diet and drugs with anti-oxidant activities improve
      this potentially progressive disease before resulting in liver cirrhosis and
      hepatic carcinoma.

PMID- 14598661
TI  - [A case of psoriatic arthropathy complicated with HTLV-I carrier and secondary
      amyloidosis].
AB  - We report a case of psoriatic arthropathy complicated with HTLV-I carrier and
      secondary amyloidosis. She was a 45-year-old woman and was diagnosed as psoriatic
      arthropathy and HTLV-I carrier in December 1999. She was treated with combination
      therapy corticosteroid, salazosulfapyridine, methotrexate, cyclophosphamide, and
      gold sodium. However, her arthralgia and fever was not completely improved. In
      April in 2001, she was admitted to our hospital because of nausea, vomiting, and
      diarrhea. Her colon fiberscopic examination showed rubber, erosion, and multiple
      ulcers of the rectum through descending colon mucosa. Her biopsied specimens of
      the colon mucosa showed Congo Red dye stained amyloid deposits. Because the loss
      of stain for Congo Red dye after exposure to potassium permanganate, the deposits
      were amyloid A protein. This case is considered as a rare case of psoriatic
      arthropathy and HTLV-I carrier complicated with secondary amyloidosis in a
      relatively short period (approximately two years) after onset of psoriatic
      arthropathy.

PMID- 14598662
TI  - [A case of Poncet's disease (tuberculous rheumatism) in a patient with chronic
      renal failure undergoing hemodialysis therapy].
AB  - A 78-year-old man who was undergoing hemodialysis therapy was admitted to our
      hospital because of sore throat, remittent cervical lymphadenopathy, and
      polyarthritis over the preceding 4 weeks. On admission, he had bilateral cervical
      lymphadenopathy. He complained of arthralgia associated with tenderness, warmth
      and swelling of both elbows, left side wrist and left shoulder joint. The C
      reactive protein level on admission was 15.3 mg/dl. Rheumatoid factor,
      antinuclear antibodies, tuberculin skin test and blood culture were negative.
      Joint fluid was not aspirated. Radiographs of the joints did not reveal any
      abnormalities. Acid-fast bacilli were demonstrated in the smear of the cervical
      lymph node with a fluorochrome rhodamine-auramine stain. Mycobacterium
      tuberculosis DNA was identified by polymerase chain reaction. We found the
      presence of caseating granuloma on the biopsy specimens and M.tuberculosis was
      detected from culture. At that point, we diagnosed this patient as having
      tuberculous lymphadenitis. His general symptoms resolved rapidly after starting
      with a three-drug regimen consisting of isoniazid, rifampin and pyrazinamide. His
      polyarthritis also improved dramatically. Finally we considered that his
      polyarthritis was tuberculous rheumatism, also called Poncet's disease. Poncet's
      disease is characterized by sterile polyarthritis during active tuberculosis
      infection. It is considered a reactive arthritis, which is a different entity
      from tuberculous arthritis. Although this is a rare disease, we should be aware
      of it in hemodialysis patient clinics, because the incidence of tuberculosis
      infection has been reported to be increasing in patients with end-stage renal
      failure.

PMID- 14598663
TI  - [Case of vascular Behcet's disease initially presented with Burger's disease-like
      vasculitides].
AB  - The patient was a 24-year-old man. Burger's disease was diagnosed initially based
      on the finding of bilateral radial artery obstruction, and the patient underwent
      vascular reconstructive surgery. After the operation, however, formation of false
      aneurysms was observed frequently in the left brachial artery at the elbow, which
      necessitated performance of vascular reconstructive surgery up to five times in
      total, including of the right common femoral artery, which had been punctured
      several times for investigational procedures. During the clinical course, fever,
      oral aphthoid ulcers, genital ulcers, and nodular erythema appeared, and
      incomplete Behcet's disease was diagnosed. Histopathological examination
      suggested that the vascular lesion was consistent with necrotizing angiitis. The
      systemic inflammatory findings and angiitis improved following steroid
      administration. Vascular Behcet's disease is known as a special type of Behcet's
      disease, but usually develops in the patients with a long history of the disease.
      Our patient was believed to be very instructive because, when Behcet's disease
      occurs with angiitis and the epidemiological characteristics agree with those of
      Burger's disease like in our patient, differentiation may be difficult.

PMID- 14598664
TI  - [Case of systemic sclerosis presenting with alveolar hemorrhage and positive anti
      neutrophil cytoplasmic myeloperoxidase antibody(MPO-ANCA) without pathological
      renal involvement].
AB  - We report a 54-year-old woman with systemic sclerosis who presented alveolar
      hemorrhage. She noticed shortness of breath in May 1997. She was diagnosed having
      interstitial pneumonitis and systemic sclerosis with sclerodactylia of bilateral
      fingers in December. She developed bloody sputum and dyspnea suddenly on March
      12, 1999. Bloody lavage fluid with hemosiderin-laden macropharge was observed by
      bronchial fiber scopic examination. The elevated level of MPO-ANCA was detected
      without anti-DNA antibody. Administration of intravenous methylprednisolone(1g
      per day, 3 days) followed by 40 mg per day of prednisolone achieved complete
      response, and MPO-ANCA level was decreased. Mild proteinuria and microhematuria
      was detected on admission, but renal biopsy revealed no findings of crescent
      formation or angiitis. With coadministration of oral cyclophosphamide she doesn't
      have any renal involvement or recurrence of alveolar hemorrhage during these four
      years. MPO-ANCA level remains negative. Alveolar hemorrhage, which is uncommon
      pulmonary event in systemic sclerosis, is often coexist with renal angiitis in
      the context of "pulmo-renal syndrome". MPO-ANCA is said to be related to pulmo
      renal syndrome and is sometimes induced by D-penicillamine. This patient is
      really important in considering the pathogenesis of alveolar hemorrhage because
      she had no renal vasculitic lesions or D-penicillamine intake.

PMID- 14598665
TI  - [Hemophagocytic syndrome associated with hypercytokinemia in a patients with
      rheumatoid arthritis].
AB  - A 65-year old female, who had been suffered from rheumatoid arthritis, was
      admitted to our hospital because of fever, oral ulcers, perianal skin ulcers,
      petechiae in the both legs, hepatosplenomegaly and cervical lymphadenopathy. Her
      laboratory data showed severe anemia, leukocytopenia, and thrombocytopenia as
      well as low PT activity, prolonged APTT, decreased fibrinegen and elevated FDP.
      In addition to raised values of liver enzymes and triglyceride, marked elevation
      of several cytokines were found. IgM and IgG class antibodies to cytomegalovirus
      were demonstrated positive and their titers were 2.60 and 938.0, respectively.
      The study for the aspiration of bone marrow revealed hemophagocytosis of
      erythrocytes, leukocytes and thrombocytes. Based upon these findings, she was
      diagnosed as having hemophagocytic syndrome associated with cytomegalovirus
      infection. Steroid treatment inducing mini-pulse therapy was introduced to her
      and bought full recovery from the illness. The association of hemophagocytic
      syndrome to rheumatoid arthritis was reviewed in the literature and five cases
      were documented to have good prognosis with steroid treatment.

PMID- 14598666
TI  - [Successfully treated case with microscopic polyangiitis complicated severe
      varicella zoster virus infection including encephalitis and disseminated
      varicella zoster].
AB  - We report a case with microscopic polyangiitis (MPA) complicated by varicella
      zoster encephalitis. A 60-year-old woman caught a common cold and had acute
      otitis media in April 1998. Proteinuria and hematuria with hyaline cast were
      noted at the routine medical check in May, and she was referred to our hospital
      because of high fever and chest pain. MPA was diagnosed with acute progressive
      renal failure, pleuritis and elevated anti-neutrophil cytoplasmic myeloperoxidase
      antibody (MPO-ANCA). Corticosteroid therapy was administered under hemodialysis
      but MPA was flared several times with various symptoms including interstitial
      pneumonitis, alveolar hemorrhage and erythema multiforme exudativum. During the
      course of the disease she developed disseminated varicella zoster and
      encephalitis. Positive polymerase chain reaction to varicella zoster in
      cerebrospinal fluid helped to differentiate her encephalitis from central nervous
      system symptoms due to microscopic angiitis and herpes simplex encephalitis.
      Combination of corticosteroid and acyclovir therapies for MPA and varicella
      zoster encephalitis under hemodialysis were successful. The diagnostic process
      and therapies to these complicated contexts were thought to be very important.

PMID- 14598667
TI  - [Combined use of intrathecal morphine and diclofenac suppository for
      postoperative analgesia after caesarean section].
AB  - BACKGROUND: Intrathecal morphine for postoperative analgesia after caesarean
      section has been used in Europe and North America, but its use is not common in
      Japan. METHODS: We randomized 40 parturients to two groups, given either
      intrathecal saline (control group) or intrathecal morphine 0.05 mg (morphine
      group) for caesarean section. To both groups, we gave a diclofenac suppository 50
      mg every 8 hours after surgery. RESULTS: The area under curve for the visual
      analogue scale for pain during 24 hours after operation was significantly lower
      (P < 0.01) in the morphine group than the control group. In addition, the
      parturients who required pentazocine as a rescue analgesia was significantly
      fewer in the morphine group (5 parturients) than the control group (11
      parturients). There was no significant difference between the two groups in the
      Apgar score of infants, pH in umbilical cord arterial and venous blood and the
      incidence of postoperative nausea and vomiting. The incidence of pruritus was
      significantly higher in the morphine group (11 parturients) than the control
      group (no parturient). CONCLUSIONS: Intrathecal morphine 0.05 mg and diclofenac
      suppository 50 mg given every 8 hours produced effective postoperative analgesia
      with minimum side effects after caesarean section.

PMID- 14598668
TI  - [The effect of repeated sevoflurane anesthesia on hepatic function and
      immunological system].
AB  - BACKGROUND: Sevoflurane is known as a useful and safe anesthetic because of its
      properties of fast uptake and elimination at the lungs and of no effects on
      hepatic function. In this study we examined the effect of repeated sevoflurane
      anesthesia on hepatic function and immunological system. METHODS: Eight patients
      (ASA, PS 2 or 3) received sevoflurane anesthesia three times in 6 months. Six
      patients had emergency operation for injuries. Aspirate transaminase (AST),
      alanine transaminase (ALT) and complements (CH50, C3, C4) were measured prior to
      anesthesia, and 1, 7 and 14 days after anesthesia. RESULTS: The values of AST and
      ALT were high prior to anesthesia at the first anesthesia. However, these were of
      no significant changes. CH50, C3, C4 increased significantly after the first
      anesthesia. However, there were no significant changes of these complements after
      the second and the third anesthesia. CONCLUSIONS: Our results suggest that
      sevoflurane is not likely to provide adverse effects on the liver and to suppress
      the production of complements accompanied by the surgical stress.

PMID- 14598669
TI  - [Usefulness of monitoring forehead deep-tissue temperature as an index of core
      temperature in adult patients undergoing laparotomies under general anesthesia-
      investigation in operating rooms with air-movement control system using vertical
      flow].
AB  - BACKGROUND: Acute changes in air temperature in the vicinity of the patents'
      forehead may impair clinical usefulness of the forehead deep-tissue thermometry.
      We thus investigated usefulness of monitoring the forehead deep-tissue
      temperature as an index of core temperature in 12 adult patients undergoing
      laparotomies in operating rooms with air-movement control system using vertical
      flow. METHODS: Nasopharyngeal, forehead deep-tissue, palm deep-tissue, and
      fingertip skin-surface temperatures were recorded during surgery every 5 minutes
      in operating rooms where room temperature was thermostatically controlled at
      approximately 25 degrees C. The patients were not actively warmed with forced-air
      warmers, but covered with cotton blankets where possible. The deep-tissue and
      fingertip skin-surface temperatures were compared with the nasopharyngeal
      temperature using regression and Bland and Altman's analyses. RESULTS: The four
      temperatures continued decreasing during surgery, and the nasopharyngeal
      temperature decreased to below 36 degrees C 2 hours after induction of
      anesthesia. Only the forehead deep-tissue temperature satisfactorily correlated
      with the nasopharyngeal temperature (r = 0.76, n = 300, P < 0.0001). The
      difference between nasopharyngeal and forehead temperatures was +0.26 degree C,
      and its standard deviation was 0.34 degree C. CONCLUSIONS: The forehead deep
      tissue temperature has sufficient accuracy and precision for clinical use in
      operating rooms with air-movement control system using vertical flow. However,
      the core temperature appears to be slightly underestimated with the forehead deep
      tissue thermometry.

PMID- 14598670
TI  - [A case of hyperemia during arteriovenous malformation surgery controlled with
      beta-blocker and jugular bulb oxygen saturation (SjO2) monitoring].
AB  - The authors report a case of hyperemic complications during arteriovenous
      malformation (AVM) surgery controlled with beta-blocker. A 25-year-old male was
      anesthetized with propofol-fentanyl under jugular venous bulb oxygen saturation
      (SjO2) monitoring. Just after the total removal of AVM, SjO2 and blood pressure
      increased suddenly and brain swelling occurred. On the diagnosis of hyperemia of
      the brain, hyperventilation and controlled hypotension with nicardipine,
      diltiazem and sodium nitroprusside were started, but they were not effective.
      Thereafter, we injected a beta-blocker (propranolol, 0.2 mg) intravenously,
      resulting in the decrease in blood pressure and the disappearance of the brain
      swelling. SjO2 monitoring supports the safe management of postresection
      hyperemia, and beta-blocker can be useful against hyperemic complications during
      and after AVM surgery.

PMID- 14598671
TI  - [Respiratory management in a patient with severe tracheal stenosis caused by
      compression from the ascending aortic arch aneurysm].
AB  - In cases of tracheal compression by a mediastinal mass or aortic aneurysm, muscle
      relaxant might induce fetal ventilatory failure. It is known to be valuable to
      keep spontaneous breathing in these cases. A 42-years-old woman complicated with
      Marfan syndrome had acute respiratory failure due to acute progression of
      tracheal stenosis caused by compression from the ascending and aortic
      pseudoaneurysm. After the induction of general anesthesia for video-assisted
      thoracic surgery (VATS) for high-pneumothorax, she was placed in lateral
      position. Suddenly it became difficult to ventilate her and her oxygenation
      saturation declined with bradycardia. We returned her to supine position and then
      could manage to ventilate her easier. But we could not maintain stable
      ventilation until her spontaneous breathing appeared. VATS was cancelled and she
      was brought in to the ICU after extubation. In the ICU she developed respiratory
      distress again soon and was reintubated under consciousness guided by
      bronchofiber scope. We managed successfully to keep spontaneous breathing intact
      under proper sedation by three sedative drugs; propofol, midazolam and morphine
      for 5 days until the next operation. We realized the importance of maintaining
      spontaneous breathing under proper sedation in a case of severe tracheal
      stenosis.

PMID- 14598672
TI  - [A case of silent rupture of a cerebral arteriovenous malformation during
      laparotomy].
AB  - A 52-year-old female, scheduled for rectal cancer resection, had no history of
      central nervous system abnormality. Anesthesia was maintained with general
      anesthesia combined with epidural anesthesia. Her only hemodynamic change was a
      rise in arterial pressure to 140 mmHg just after the start of the operation.
      However, postoperatively she failed to be aroused and she exhibited a positive
      Babinski's sign, anisocoria, an absent light reflex and paresis of the left lower
      extremity. Cerebral vascular accident was suspected and a CT scan revealed a
      cerebral hematoma which was immediately removed surgically. Upon exploration,
      abnormal vessels were recognized and we diagnosed an acute rupture of
      arteriovenous malformation. She fully recovered consciousness immediately after
      the operation. Her postoperative course was uneventful, except for a residual
      paresis of the left lower extremity.

PMID- 14598673
TI  - [A case of urgent aortic valve replacement for infective endocarditis in
      pregnancy].
AB  - A 31-year-old woman underwent urgent aortic valve replacement due to infective
      endocarditis at 16 weeks' gestation. Because of rapid and severe congestive heart
      failure, maternal rescue was regarded as the priority in the anesthetic
      management. Previous literature shows that high-flow high-pressure normothermic
      perfusion during cardiopulmonary bypass provides the best way of reducing fetal
      risk. Though it was not performed, the fetus was alive for 24 hours after the
      operation. Perioperative administration of dopamine and furosemide could have
      diminished uterine blood flow. If these drugs could have been avoided, the fetus
      may have stayed alive. However, considering the risk of teratogenesis due to drug
      administration and cardiopulmonary bypass, propriety of pregnancy prolongation is
      controversial.

PMID- 14598674
TI  - [Cardiac arrest during emergency cesarean section due to peripartum
      cardiomyopathy--a case report].
AB  - A 23-year-old woman at 35 weeks of gestation was scheduled for emergency cesarean
      section because of preeclampsia. Anesthesia was induced with thiopental 250 mg,
      and her trachea was intubated following administration of vecuronium 7 mg.
      Anesthesia was maintained with oxygen and sevoflurane (0.5%). Immediately after
      the start of the surgical procedure, she developed severe bradycardia and
      hypotension followed by cardiac arrest. She was resuscitated, and her heart beat
      resumed 30 min after the start of the resuscitation. Her babies were delivered
      without sequela during resuscitation. She was transferred to the intensive care
      unit of our university hospital. She was diagnosed as having peripartum
      cardiomyopathy from her history and echocardiography. She was discharged from the
      hospital with only slight disturbance of consciousness two months after surgery.

PMID- 14598675
TI  - [A case of intractable bone fracture pain due to metastasis of carcinoma treated
      with continuous epidural infusion using ropivacaine].
AB  - A 62-yr-old man presented with intractable pain due to sciatic and iliac bone
      fractures with metastasis of carcinoma. We treated this symptom using epidural
      infusion of ropivacaine over 8 weeks. He developed no complications related to
      epidural infusion of ropivacaine. Continuous epidural infusion of ropivacaine is
      useful for the management of pain from invasive carcinoma.

PMID- 14598676
TI  - [A patient with HTLV I-associated myelopathy (HAM) complaining of burning pain on
      the bilateral feet: a case report].
AB  - A 67-year-old man complained of a burning pain and weakness of bilateral feet
      after contusion of the left lumbar region. Skin as well as bone dystrophy and
      disturbance of bladder function were not seen, but low skin temperature was
      observed in the left lower leg. Glove anesthesia was seen on bilateral feet.
      Patellar tendon reflex was accentuated but Achilles tendon reflex was diminished,
      and bilateral Babinski sign was positive. Compression of the spinal cord or
      spinal root nerve was not noticed by MRI, myelography and myelo-CT (from cervical
      to lumbar level). We suspected the complex regional pain syndrome type I, and
      performed sympathetic blockade, but burning pain was not relieved. We looked for
      spinal tumor, myelitis, collagen disease, vitamin deficiency and malignancy but
      could not find out any disorder. However, the patient had neuropathic sign in
      electromyogram, and high anti-HTLV-I antibody titers in blood serum (8192x) and
      cerebrospinal fluid (256x). We diagnosed this case as HTLV I-associated
      myelopathy (HAM). He developed, so called, HTLV I-associated pneumonia at 74
      years of age. We suggest that HAM may rarely accompany a burning pain and
      neuropathy (not myelopathy) as main symptoms. The present case suggests that a
      patient with HAM may develop HTLV I-associated pneumonia during its process;
      indicating a new concept of this very rare disease.

PMID- 14598677
TI  - [A case of delayed diagnosis of pulmonary thromboembolism in a patient with
      mitral stenosis undergoing cesarean section].
AB  - Cesarean section was performed under general anesthesia in a 38-year-old patient
      with congestive heart failure due to severe mitral stenosis. During surgery,
      pulmonary hypertension, right ventricular distension and the dissociation of
      PETCO2 and PaCO2 were observed. However, pulmonary thromboembolism (PTE) was
      proved after the operation when she developed severe hypotension in the intensive
      care unit. Although she recovered once from circulatory unstability with the use
      of percutaneous cardiopulmonary support (PCPS) and she could be weaned from PCPS
      at the 4th postoperative day, she died from tracheal bleeding and recurrent
      cardiopulmonary collapse 22nd day after the surgery. It should be noted that the
      increasing dissociation of PETCO2 and PaCO2 may be an early sign of PTE even in a
      patient with severe mitral stenosis and pulmonary hypertension.

PMID- 14598678
TI  - [A case of undiagnosed "takotsubo" cardiomyopathy during anesthesia].
AB  - "Takotsubo" cardiomyopathy is characterized by transient left ventricular
      dysfunction. We have reported a case of "Takotsubo" cardiomyopathy unrecognized
      during anesthesia because of no ischemic changes in monitored electrocardiogram
      (ECG). The patient was an 80-year-old woman undergoing open reduction surgery for
      fractures of the left tibia and ulna. Anesthesia was maintained with O2, N2O,
      sevoflurane and fentanyl. Sinus tachycardia was noted throughout anesthesia which
      was unresponsive to fluid loading and blood transfusion. ECG of limb leads showed
      no ST-T changes or abnormal Q waves and the blood pressure was stable during
      anesthesia. Postoperative echocardiography showed extensively decreased left
      ventricular wall motion with akinesis of the anterior wall and anterior septum
      from the mid-papillary level to apex. ECG showed negative T waves in V2-V6
      without abnormal Q waves or ST changes. The increase in CPK-MB was very little.
      The abnormal left ventricular wall motion was completely recovered on the third
      postoperative day. Her perioperative cardiac event was diagnosed as "Takotsubo"
      cardiomyopathy by reversible ampulla-shaped ventricular dysfunction. She had no
      symptoms throughout the perioperative period and recovered without any sequela.

PMID- 14598679
TI  - [Anesthesia for laparoscopic cryptorchidpexy in a patient with congenital
      myopathy].
AB  - A relatively high incidence of malignant hyperthermia (MH) and an unpredicted
      (usually increased) sensitivity to muscle relaxants are reported in patients with
      congenital myopathies (CM). We present a case of anesthetic management of a
      patient with a clinical diagnosis of CM. An 18-month-old, 11.3-kg, male patient,
      who had received a diagnosis of CM, was scheduled for the laparoscopic
      cryptorchidpexy. Anesthesia was induced with propofol and fentanyl, and the
      trachea was intubated without muscle relaxants. An epidural catheter was inserted
      via the sacral hiatus, the tip of which was located at the second lumbar level
      for a purpose of obtaining not only pain relief but also muscle relaxation.
      Anesthesia was maintained with propofol, nitrous oxide and fentanyl, combined
      with epidural anesthesia. The anesthetic course was uneventful with enough pain
      relief and good muscle relaxation.

PMID- 14598680
TI  - [A case of acute pneumococcal meningitis treated with spinal drainage and
      vancomycin administration].
AB  - A 25-year-old woman complaining of general fatigue, headache, high fever, and
      nuchal rigidity, was admitted. She was diagnosed as pneumococcal
      meningoencephalitis after the cell culture of cerebrospinal fluid (CSF). Despite
      the administration of vancomycin (VCM), she fell into a coma without amelioration
      of the symptom. VCM was replaced by pipellaciline because antibacterial
      sensitivity showed the pneumococci were sensitive to the penicillins. She
      remained unconscious showing progressive hydrocephalus after the open drainage
      operation. The lumbar drainage at the L 4-5 level and the intrathecal
      administration of VCM were performed to improve the mal-circulation of CSF. After
      the procedure, the cell count of CSF showed a significant decrease and her
      consciousness level was recovered gradually. The patients with pneumococcal
      meningitis may occasionally require the lumbar drainage with the intrathecal
      administration of appropriate antibiotics, in case they fail to show response to
      the conventional therapy.

PMID- 14598681
TI  - [ECG changes during emergence from anesthesia in a patient with LEOPARD
      syndrome].
AB  - LEOPARD syndrome is a rare congenital disease characterized by seven features.
      Besides the original clinical manifestations, hypertrophic cardiomyopathy was
      reported as an additional laboratory finding recently. We gave general anesthesia
      to a child of this syndrome, and encountered ECG changes during emergence from
      anesthesia. The diagnosis was made in her infancy, and had been receiving beta
      blocker treatment ever since. The preoperative examination showed remarkable
      right axis deviation in ECG, and asymmetric ventricular septal hypertrophy in
      echocardiography. After the operation, several kinds of arrhythmia (i.e.
      atrioventricular junctional rhythm, atrioventricular dissociation, etc), were
      observed and they continued for a few minutes. Careful planning for the
      perioperative management of this syndrome is mandatory. The cardiomyopathy must
      be examined beforehand. We made an effort to prevent the extreme changes of pre-
      and after-load during the general anesthesia.

PMID- 14598682
TI  - [Anesthetic management of a patient with suspected pseudothrombocytopenia].
AB  - A 74-year-old male was operated for sigmoid colon cancer. Because of an
      agglutination of the patient's platelet, it was difficult to measure his platelet
      count under ethylene diamine tetra acetate (EDTA), heparin or citrate as
      anticoagulants with an automated cell counter. Even though there was a strong
      possibility of pseudothrombocytopenia, anesthetic management for the patient was
      safely conducted. His condition was stable throughout the perioperative course
      and no bleeding tendency was observed. Nitrous oxide, oxygen, sevoflurane,
      propofol and pancuronium were useful in this case.

PMID- 14598683
TI  - [A case of emergency surgery in a patient with bronchial asthma under continuous
      spinal anesthesia].
AB  - A 78-year-old male, observed for bronchial asthma, underwent two emergency
      operations within eight days. The first operation was performed under general
      anesthesia with tracheal intubation. Anesthesia was maintained by sevoflurane
      oxygen and continuous infusion of propofol in combination with epidural injection
      of lidocaine. During the operation, respiratory sound was almost clear. But
      wheezing occurred as he awoke after discontinuation of the anesthetics. He needed
      ventilatory support for three days for status asthmatics. The second operation
      was performed under continuous spinal anesthesia using hypobaric tetracaine and
      hyperbaric bupivacaine. No ventilatory support was necessary after the operation
      and he was discharged uneventfully.

PMID- 14598684
TI  - [A case of cor triatriatum diagnosed by echocardiography on pre-anesthetic
      examination].
AB  - A 69-year-old man was planned for elective surgery of the lumbar vertebral disk
      herniation. We performed a pre-anesthetic examination. He had a mild cardiomegaly
      (CTR = 55%) on chest X-ray examination, and ST-T change on electrocardiogram. His
      electrocardiogram showed negative T wave in III and aVF, ST elevation in I, aVL,
      V1-3, and flat T wave in V5-6. But he was without any symptoms of chest
      occlusion. He had no other abnormal laboratory data and abnormality in physical
      examination. We did echocardiography on him and cor triatriatum was diagnosed.
      The flow from the accessory chamber was 0.44 m.s-1. There were no abnormalities
      in the reflux of the pulmonary vein. We managed him under general anesthesia for
      operation, and took care to prevent right heart failure. There were no
      complications in peri-operative period. It was very important to perform pre
      anesthetic examination by anesthetic specialist. Echocardiogram is useful for pre
      anesthetic examination, if cardiovascular disease is suspected by chest symptom,
      electrocardiogram or chest X-ray examination.

PMID- 14598685
TI  - [The relationship between the yearly number of operations and mortality due to
      intraoperative critical incidents in patients for cardiac surgery: an analysis of
      annual survey 2001 conducted by the Japanese Society of Anesthesiologists].
AB  - BACKGROUND: The number of surgical operations performed has been reported to have
      a relation with surgical morbidity and mortality. In Japan, however, the
      relationship between surgical load and outcome has not been elucidated. METHODS:
      We investigated this relationship in patients for cardiac surgery using data from
      the 2001 annual survey concerning anesthesia-related critical incidents,
      conducted by the Committee on Operating Room Safety, Japanese Society of
      Anesthesiologists. Between January 1, 2001 and December 31, 2001, 43,411 patients
      for cardiac surgery patients were registered from 486 training hospitals
      certified by the Japanese Society of Anesthesiologists. Intraoperative critical
      incidents occurred in 632 of the patients. Of these, 289 patients died within 7
      postoperative days. The overall mortality was 66.57 per 10,000 anesthetics.
      Hospitals were divided into 4 groups according to their annual numbers of cardiac
      operations: Group A, fewer than 50; Group B, 50-99; Group C, 100-199; Group D,
      more than 200. Mortality rate was expressed as a mean +/- SD (95% confidence
      interval). RESULTS: The mortality rates in Group A-D were 107.64 +/- 327.33
      (63.47-151.81), 114.42 +/- 168.76 (83.02-145.87), 63.53 +/- 84.35 (48.04-79.01),
      and 36.97 +/- 52.83 (22.32-51.61) per 10,000 anesthetics, respectively.
      CONCLUSIONS: The yearly number of operations has been shown to affect mortality
      rate due to intraoperative critical incidents among patients for cardiac surgery
      in Japan. Hospitals with a small number operations should pay significant
      attention to improving surgical outcome. These results also suggest that
      centralization or regionalization of cardiac surgery should be discussed from the
      socio-economical points as well as patient safety.

PMID- 14598686
TI  - [Urinary continence after radical retropubic prostatectomy: a modification in the
      technique of apical dissection].
AB  - Urinary incontinence impairs the quality of life for patients following radical
      prostatectomy. We retrospectively reviewed the records of 36 patients who
      underwent radical retropubic prostatectomy between 1987 and 2002, and achieved
      the time from operation until urinary continence. A modification in the technique
      of apical dissection was introduced in 1999 and applied in 12 cases of
      consecutive radical prostatectomy. The principles for this technique were based
      on sharp division of the dorsal vein complex, continuous suturing cut edges of
      lateral pelvic fascia, and anterior anastomotic sutures including lateral pelvic
      fascia as well as urethra and bladder neck. None of the patients undergoing the
      new technique used pads at 6 months. With introduction of this technique, the
      rate of continence at 12 months increased from 58.3 to 100.0%. Our results
      suggest that the surgical technique of apical dissection is an important factor
      associated with postprostatectomy in continence.

PMID- 14598687
TI  - [Two-week administration of low-dose Hachimi-jio-gan (Ba-Wei Di-Huang-Wan) for
      patients with benign prostatic hyperplasia].
AB  - We evaluated the efficacy and side effects of two-week administration of low-dose
      "Hachimi-jio-gan (Ba-Wei Di-Huang-Wan)" for 41 patients with benign prostatic
      hyperplasia and searched for any predictors of good response to this agent.
      Although two of the 41 patients could not finish administration due to epigastric
      discomfort, there were no other side effects. "Hachimi-jio-gan" significantly
      reduced scores of emptying, weak stream, total score and quality of life score
      according to the International Prostate Symptom Score, although the degree of
      reduction was inferior to that induced by tamsulosin administration. "Hachimi-jio
      gan" significantly improved max flow rate, and the degree of this improvement was
      superior to that induced by tamsulosin administration. Approximately 40% of
      patients were good responders to "Hachimi-jio-gan" therapy. Severe sensation of
      incomplete emptying was a predictor of good response.

PMID- 14598688
TI  - [Treatment results of radical prostatectomy in clinical stage B and C prostate
      cancer: comparison of the neoadjuvant therapy group versus the surgery group;
      retrospective analysis of 80 cases].
AB  - Between 1994 and 2001, 80 patients underwent radical prostatectomy without
      adjuvant therapy for clinical stage B and C prostate cancer. The patients were
      not treated with adjuvant therapy before biochemical prostate specific antigen
      (PSA) failure. Of all 80 patients, 35 patients (43.8%) received neoadjuvant
      hormonal therapy prior to radical prostatectomy (the neoadjuvant therapy group),
      45 patients (56.2%) underwent prostatectomy alone (the surgery alone group).
      Retrospective analysis to evaluate the effects of neoadjuvant therapy was
      performed from clinicopathological findings and the biochemical PSA failure-free
      rate. Of all patients, 58 (72.5%) were in clinical stage B and 22 (27.5%) were in
      clinical stage C. Of 58 patients in clinical stage B, 19 (32.8%) underwent
      prostatectomy combined with neoadjuvant therapy. Of the 22 patients in clinical
      stage C, 17 (77.3%) underwent prostatectomy combined with neoadjuvant therapy.
      Pathologically, 37 (46.3%) were in stage B, 38 (47.5%) in stage C and 2 (2.5%) in
      stage D1. Three patients in the neoadjuvant therapy group had no malignant
      findings in specimens of prostatectomy. In comparison with the clinical stage,
      pathologically 8 (22.9%) showed overstaging, 4 (5.0%) understaging and 23 (28.8%)
      accurate staging in the neoadjuvant therapy group, respectively, 0 (0.0%), 20
      (44.4%), and 25 (55.6%) in the surgery alone group. In clinical stage B and C,
      there was no significant difference in the biochemical PSA failure-free rate
      between the neoadjuvant therapy group and the surgery alone group. On the other
      hand, in pathological stages B, the 5-year PSA failure-free rate was 63.2% in the
      neoadjuvant therapy group, but 100% in the surgery alone group. Although
      neoadjuvant therapy may have some effect on downstaging, our retrospective
      analysis suggests that it has no significant effect on PSA failure-free rate.

PMID- 14598689
TI  - [Change of serum adrenal androgens in prostatic cancer patients after bilateral
      orchidectomy or LHRH agonist treatment].
AB  - Bilateral orchidectomy (ORX) or administration of luteinizing hormone releasing
      hormone agonist (LHRH) for prostatic cancer patients causes suppression of
      testicular androgens. However, the suppression of adrenal androgens by these
      treatments is controversial. We measured serum concentrations of testosterone
      (T), 4-androstene-3, 17-dione (A-dione), dehydroepiandrosterone (DHEA), LH,
      follicle-stimulating hormone (FSH), adrenocorticotropic hormone (ACTH) and
      cortisol before and after 3-12 months of the first hormonal treatment in 17
      prostatic cancer patients who had received ORX (8 cases) or LHRH (9 cases). ORX
      and LHRH decreased serum T to the castration level significantly (ORX: p < 0.001,
      LHRH: p < 0.0001). ORX increased serum LH and FSH significantly (LH: p < 0.001,
      FSH: p < 0.001), whereas LHRH decreased LH and FSH significantly (LH: p < 0.05,
      FSH: p < 0.05). Neither treatment caused any significant change in ACTH or
      cortisol. ORX and LHRH decreased the serum A-dione significantly (ORX: p < 0.01,
      LHRH: p < 0.001). LHRH decreased the serum DHEA significantly (p < 0.01), whereas
      ORX did not decrease serum DHEA. These data suggest that "medical" and "surgical"
      castration, especially LHRH agonist, may decrease not only testicular androgens
      but also adrenal androgens.

PMID- 14598690
TI  - [A case of renal capsular liposarcoma].
AB  - A 70-year-old man was admitted to our hospital with microscopic hematuria.
      Abdominal echography, computed tomography and magnetic resonance imaging revealed
      renal capsular tumor, and radical nephrectomy was performed. The tumor was
      diagnosed histopathologically as liposarcoma (well differentiated type). This
      tumor did not invade the renal parenchyma but extended from the upper pole to the
      lower pole on the surface of the renal capsule. He has been alive without disease
      for 14 months after surgery.

PMID- 14598691
TI  - [A case of idiopathic adrenal hemorrhage].
AB  - A 67-year-old woman underwent abdominal ultrasonography as part of a general
      health examination and was incidentally found to have a mass 5 cm in diameter in
      the left adrenal gland. She had no experience of abdominal trauma. Computerized
      tomography (CT) revealed a 5.5 x 5.0 cm mass in the left adrenal gland, which was
      heterogeneously enhanced by the contrast medium. Hormanal data for adrenal
      function were all within the normal range. For the suspected non-functioning
      adrenal tumor, the patient underwent adrenalectomy. Histopathological examination
      demonstrated only hematoma without tumor cells.

PMID- 14598692
TI  - [A case of Lambert-Eaton myasthnic syndrome associated with small cell lung
      carcinoma representing as urinary retention].
AB  - A 65-year-old male was admitted with the chief complaint of voiding difficulty on
      28 October, 2001. He was in the state of urinary retention. Urological
      investigation including cystosocopy, urethrocystography, and urodynamic study
      revealed an areflex-type bladder, according to the new International Continence
      Society (ICS) classification with no prostatic urethral obstruction. He was
      diagnosed with neurogenic bladder although the cause of detrusor areflex was
      unknown. Because all medication was ineffective, transurethral resection of
      prostate was performed on 11 January, 2002, but urinary retention could not be
      relieved. After operation, he complained of muscle weakness of upper extremities
      and poor control of bowels. He was diagnosed with Lambert-Eaton myasthenic
      syndrome associated with small cell lung carcinoma. His myasthenic symptoms,
      including autonomic symptoms were relieved after chemotherapy and radiation for
      small cell lung carcinoma.

PMID- 14598693
TI  - [Tuberculous epididymitis caused by intravesical BCG therapy: a case report].
AB  - We describe a case of tuberculous epididymitis that occurred 35 months after
      completion of a course of intravesical Bacillus Calmette-Guerin (BCG). A 67-year
      old man had received trasuretheral resection for bladder cancer in February 1997.
      Two weeks after the operation, a course of 8 weekly intravesical instillations of
      BCG (Tokyo 172 strain) was carried out between March and April, 1997. Under the
      diagnosis of benign prostatic hypertrophy, transuretheral resection of the
      prostate was performed in March 1998. Multiple tuberculous nodules were
      histopathologically detected in resected prostatic tissues. The patient
      complained of a small nodule in the right epididymal tail in August 2001. The
      nodule developed during 6 weeks, with spontaneous perforation of the scrotal skin
      and discharge of pus. The pus contained acid-fast bacilli, which were shown to be
      tubercle bacilli by polymerase chain reaction (PCR) with pan-mycobacterium
      primer. MPB64-T2, T6 and pncA-7, 11C were positive, while PT-1, 2 and pncA-7, 10
      were negative by PCR. These results revealed that Mycobacterium bovis (BCG
      Organism) was the cause of the epididymitis. Drug therapy for 3 months with
      rifampicin, isoniazid and ethambutol was initiated in September 2001, and right
      orchiectomy was performed in October. Histopathological examination showed
      tuberculous epididymitis. In this case, persistent BCG organisms may have reached
      the epididymis from the prostate, and may have been activated by
      immunosuppression associated with aging. In addition, PCR with species-specific
      primers was useful in differentiating Mycobacterium bovis from Mycobacterium
      tuberculosis.

PMID- 14598694
TI  - [A case of CA19-9 producing transitional cell carcinoma of the ureter].
AB  - We report a case of CA19-9 producing urothelial carcinoma of the right ureter. A
      61-year-old male patient who had an extremely high value of serum CA19-9 (1,185
      U/ml) with right hydronephrosis was referred to us. Magnetic resonance urography
      and retrograde ureterography revealed a long irregular filling defect in the
      right distal ureter. Under the diagnosis of right ureteral tumor, we performed
      right total nephroureterectomy and pelvic lymphadenectomy. The tumor was
      histologically diagnosed as grade 1 transitional cell carcinoma and pelvic
      lymphnodes were positive (pT1N2M0). The tumor cells showed positive
      immunostaining for CA19-9. The serum CA19-9 level was normalized after the
      operation and successive adjuvant chemotherapy (M-VAC 2 course). No recurrence
      was found for 15 months after operation. In this case, the serum CA19-9 level was
      useful as a tumor marker.

PMID- 14598695
TI  - [Intractable duodenocutaneous fistula after nephrectomy for stone pyonephrosis:
      report of a case].
AB  - A 56-year-old woman was admitted to our hospital for treatment of right stone
      pyonephrosis with a perirenal abscess. After right nephrectomy for the
      pyonephrosis, the patient suffered from post-operative bleeding, which was
      stopped by closing off the drain tube with a clamp. However, a right
      retroperitoneal abscess with gas formation developed nine days after the
      operation, necessitating an operative procedure for drainage. Pus culture
      revealed Staphylococcus epidermidis and Candida albicans. Discharge from the
      drain tube became dark green days after the drainage procedure. Upper
      gastrointestinal series revealed a duodenal fistula, which could not be closed
      using a retroperitoneal approach, so the operative wound was left open. Because
      of the volume of discharge (800-1,400 ml/day), somatostatin analogue, 100
      micrograms, was injected subcutaneously twice a day. Discharge decreased by one
      half within 2 weeks of the administration of somatostatin analogue. However, the
      duodenocutaneous fistula had not resolved over a period of 8 months. Since the
      patient developed acute cholecystitis, both cholecystectomy and closure of the
      duodenocutaneous fistula were performed transperitoneally. The duodenocutaneous
      fistula, which was closed with Endo GIA (35 mm), had protruded from a descending
      portion of the duodenum like the diverticulum. The postoperative course was
      uneventful. We speculated that the fistula occurred as a result of the
      inflammation with the abscess formation.

PMID- 14598696
TI  - Leiomyosarcoma of the spermatic cord: a case report.
AB  - A 61-year-old man presented to our hospital with a 1.5-year history of a
      gradually enlarging mass in the left scrotum. The mass was apart from the testis
      and fixed to the spermatic cord. The firm consistency and heterogeneous
      expression on ultrasonography suggested a malignant tumor. Orchiectomy with high
      ligation of the spermatic cord was performed and a histological examination
      revealed leiomyosarcoma of the spermatic cord. Distant metastases were not
      observed. Because the incidence of local recurrence has been reported to be high,
      we performed irradiation to control the disease. At 32 months post-surgery he was
      alive with no evidence of disease.

PMID- 14598697
TI  - [Cases of bacillus Calmette-Guerin-induced granulomatous prostatitis and
      prostatic stromal invasion of the bladder carcinoma in situ, showing similar
      clinical findings].
AB  - Intravesical instillation of bacillus Calmette-Guerin (BCG) is the first-line
      therapeutic option for flat carcinoma in situ (CIS) of the bladder. Intravesical
      BCG instillation has been demonstrated to cause granulomatous prostatitis.
      Bladder CIS often also is known to show prostatic stromal invasion. We report a
      case of BCG-induced granulomatous prostatitis and a case of prostatic stromal
      invasion of bladder CIS accompanied by locally advanced prostate cancer, which
      showed similar clinical findings after the intravesical BCG therapy. In these 2
      patients, urinary symptoms such as dysuria were prolonged regardless of anti
      tuberculous medication, hard nodules were palpable at the prostate, and
      hypoechoic lesions were visualized by transrectal ultrasound. Both patients were
      treated by transurethral resection of the prostate, and the diagnoses were made
      by histopathological examination. Urinary symptoms were resolved in both patients
      after surgery, but the prostatic stromal tumor showed recurrence of growth. We
      report the usefulness of transurethral resection of the prostate for medication
      resistant BCG-induced granulomatous prostatitis, and the importance of the
      correct diagnosis of prostatic stromal invasion of bladder CIS especially in the
      cases with concurrent prostate cancer.

PMID- 14598698
TI  - [A case of retroperitoneal mucinous cystadenocarcinoma].
AB  - A 61-year-old woman was admitted to our hospital for right abdominal mass.
      Various examinations revealed a retroperitoneal tumor. Open surgery was
      performed. Pathological findings revealed a mucinous cystadenocarcinoma. We
      review and discuss 24 cases of retroperitoneal mucinous cystadenocarcinoma
      reported in Japan.

PMID- 14598699
TI  - [Primary carcinoid of the testis: a case report].
AB  - A 66-year-old male was hospitalized with right femur fracture and injury of the
      popliteal artery sustained in a traffic accident. The patient underwent external
      fixation and repair of popliteal artery. At operation, the orthopedists noticed a
      mass in the scrotum and requested our consultation. A right orchiectomy was done
      under the diagnosis of a testicular tumor. The tumor measured 9 x 6 x 5 cm in
      size. Histological diagnosis was pure carcinoid of the testis. Computerized
      tomography and other studies showed no tumorous lesions elsewhere. Symptoms of a
      carcinoid syndrome were not noted. No evidence of metastasis has been seen for 12
      months after surgery.

PMID- 14598700
TI  - [A case of perineal abscess due to urethral fistula in a patient with spinal cord
      injury].
AB  - We report a case of perineal subcutaneous abscess due to urethral fistula in a
      patient with spinal cord injury. A 39-year-old male visited our hospital
      complaining of left scrotal swelling and fever. The left scrotum and perineal
      skin were swollen to the size of a goose egg, and pus was discharged from the
      perineal swollen bump. Magnetic resonance imaging (MRI) suggested an urethral
      fistula with a large subcutaneous abscess. The abscess was resected with
      debridement of necrotic tissue, and a cystostomy was placed. Endoscopy revealed a
      fistula in the bulbar urethra. The characteristics of this rare entity are
      discussed.

PMID- 14598702
TI  - [Effect of solvent exposure on autonomic nervous function in female workers at
      factories of Buddhist altar].

PMID- 14598701
TI  - [Overwork and its health effects--current status and future approach regarding
      Karoshi].
AB  - The word karoshi, i.e. death due to overwork, is not defined for medical
      diagnosis, but in Japan it means cases of compensation awarded by reason of fatal
      occupational diseases, particularly ischemic heart diseases and cerebrovascular
      diseases which are recognized as caused by a heavy workload. Current studies have
      shown that 1) almost definitely there is evidence of an association between
      overwork and cardiovascular diseases and the risk factors were found, 2) no
      reports have been published on evidence of a causal relationship between overwork
      and fatal effects even though the possibility remains, and 3) the adverse health
      effects can vary according to workers' characteristics such as gender, age,
      stress coping and perception. Recently there has been an increase in the
      proportion of compensated cases versus claims from 3.1% in the 1988 fiscal year
      to 20.7% in the 2001 fiscal year. This may be related to the deregulation of
      criteria for compensation, or nintei-kijun. The period of determination of
      overwork for victims has been extended to a maximum of six months in the newest
      criteria set in 2001, up from only one week in the criteria set in 1987.
      According to sociological analysis, long working hours in Japan are related not
      only to the structure of the working-time system but also the sociocultural
      background of labor. In 2002, the Japanese government provided the first
      countermeasures for the prevention of karoshi for all employees stating that they
      should not work more than 45 h overtime per month and that government
      intervention in the form of administrative guidance to employees and their
      employers should be conducted if overtime exceeds 100 h per month. It is a
      population strategy targeting all workers equally, not just a high-risk strategy
      targeting only those with some risk factors, and is expected to provide more
      fruitful results with flexibility, i.e. differentially reinforced management for
      older workers and those working under highly stressful conditions with
      harmonization of the production cycle in the workplace. Occupational health
      professionals such as occupational health physicians and nurses will play a key
      role in making break-throughs to solve various problems related to karoshi, which
      may then result in further investigations to provide scientific evidence for
      policy making.

PMID- 14598703
TI  - [Study on the mass-screening level of after-meal blood sugar level].
AB  - Although the blood sugar level (BS) is known to rise after a meal, it is not
      always easy to take blood from examinees in mass checkups, and persons with
      impaired glucose tolerance often have to be picked out with reference to the
      upper normal limit of fasting BS. In our survey of a large number of health check
      examinees (free of diseases under treatment), the mean (M) fasting BS + 2
      standard deviations (SD) was close to 110 mg/dl, which is generally accepted as
      the screening level of fasting BS. When the screening level ws set at M + 2SD for
      each time span after a meal, the ratio of the screened was also close to that on
      fasting. Accordingly, the nearest round number ending either with 0 or 5 for the
      first digit is suggested to be of practical use for the screening level of after
      meal BS. In addition, as the M + 2SD for 3 h or more after a meal was almost
      identical to that on fasting, the BS at the time may be regarded as that on
      fasting.

PMID- 14598704
TI  - [Study on the mass-screening of after-meal serum triglyceride concentration].
AB  - The serum triglyceride concentration (TG) tested in health checks after meals
      cannot properly sort out hypertriglyceridemia with reference to the upper normal
      limit of fasting TG (150 mg/dl) set by the Japan Arteriosclerosis Society,
      because TG goes up considerably after a meal. In our survey of a large number of
      health check examinees (free of abnormal biochemical data other than TG and
      diseases under medical treatment), the mean (M) of fasting TG + 2 standard
      deviations (SD) was close to 150 mg/dl. When the screening level was set at M +
      2SD for each time span after a meal, the ratio of the screened was distributed
      between 19.9 and 21.8%, which was close to 23.5%, the ratio of the screened on
      fasting. Accordingly, the nearest round number ending with zero for the first
      digit is suggested to be of practical use for the screening level of after-meal
      TG. The average TG in females was definitely lower than that of males, though
      proportionately increasing with age. The ratio of the screened among females aged
      between 20 and 49 was 5.3% on fasting and 3.2-5.8% for after-meal time spans, and
      that of the screened aged in their fifties was 11.3% and 8.2-12.9% respectively.

PMID- 14598705
TI  - [Cause of cataract].

PMID- 14598706
TI  - [The inhibitory effect of aldose reductase inhibitor for proliferation in the
      lens epithelial cells of rat sugar cataract].
AB  - PURPOSE: To evaluate the inhibitory effect of aldose reductase inhibitor (ARI)
      for the accumulation of sugar alcohol and the enhanced proliferation of lens
      epithelial cells of rats fed a galactose diet. METHODS: Sprague-Dawley rats were
      fed a diet containing 50% galactose with or without ARI (SNK-860). Histological
      changes in the lenses were observed by light microscopy, and the amount of
      galactitol accumulated in the lens epithelium was measured by liquid-gas
      chromatography. Immuno-histochemical staining of proliferating cell nuclear
      antigen (PCNA) in whole-mount preparations was performed to assay the
      proliferative ability of the lens epithelial cells. RESULTS: The amount of
      galactitol in the lens epithelium and the number of PCNA positive cells in rats
      administered ARI were less than in rats fed the galactose diet. Multi-layered
      epithelium was observed in advanced cataract of rats fed the galactose diet, but
      not in the rats given ARI. CONCLUSION: The administration of ARI can prevent
      cataractous changes and aberrant proliferation of lens epithelial cells.

PMID- 14598707
TI  - [Localization of glucose and sorbitol in incubated bovine lenses using chemical
      shift imaging].
AB  - PURPOSE: To use chemical shift imaging (CSI) to measure the metabolic changes in
      glucose metabolites in bovine lenses incubated in tissue culture medium 199(TCM
      199) with a high concentration of glucose and to evaluate the viability of this
      method. METHODS: We detected an accumulation of 13C-labeled glucose and sorbitol
      in the bovine lenses incubated in TCM 199 containing 50 mM glucose-1-13C for 1,
      2, 4, or 6 days using a 2 T CSI Omega system. 1H-13C gradient-selected
      heteronuclear multiple-quantum coherence (GH-HMQC) in nuclear magnetic resonance
      (NMR), an indirect method of detecting nuclei in low sensitivity by 1H NMR, was
      used to observe 13C-enriched metabolites in the bovine lens in vivo. RESULTS: We
      found an accumulation of 13C-labeled glucose and sorbitol using the 2 T CSI Omega
      system. The level of glucose increased rapidly in the posterior segment of the
      lens as well as the anterior segment at one day after the beginning of
      incubation. Then it diminished gradually, and could no longer be detected on the
      6th day after the start of incubation possibly because of the breakdown of the
      cell membrane. The levels of sorbitol increased in the anterior area and the
      equator of the lens one day after the beginning of incubation, and remained
      unchanged for 6 days. CONCLUSION: We encountered many problems especially with
      the imaging resolution (consequently the time for measurement was prolonged), but
      this approach may be useful for non-invasive monitoring of 13C-labeled compounds.
      We believe this method will be especially useful for detecting various
      metabolites in vivo.

PMID- 14598709
TI  - [Glutamate and gamma-aminobutylic acid release into the vitreous during cataract
      surgery].
AB  - OBJECTIVE: In cataract surgery, transient retinal ischemia and photostimulation
      induced retinal damage occurs, even though only for a short duration. We
      suspected the possibility of excessive release of glutamate under these
      conditions, and therefore analyzed the amino acid contents in the vitreous body.
      MATERIALS AND METHODS: The vitreous bodies of 32 eyes with disease of the macular
      area necessitating retinovitreous surgery were used as samples for amino acid
      analysis. Ischemic diseases such as diabetic retinopathy, venous occlusion, and
      retinal detachment were excluded. The vitreous amino acid contents were compared
      between 18 eyes that underwent combined cataract and vitreous surgery and 14 eyes
      that had vitreous surgery alone. RESULTS: An approximately 3-fold increase of
      glutamate, 6-fold increase of gamma-aminobutylic acid (GABA), and 2-fold increase
      of alanine were observed in combined cataract and vitreous surgery compared to
      vitreous surgery alone. CONCLUSION: Even in human eyes, acute pressure overload
      or photostimulation for a short duration cause excessive release of glutamate. A
      simultaneous increase of GABA suggests the possibility that when glutamate is
      over-released, the retina physiologically reduced the concentration of glutamate
      via GABA, in an attempt to suppress the neurotoxin action.

PMID- 14598708
TI  - [Clinical evaluation of measurement method for antigen specific IgE in tears of
      patients with allergic conjunctival disease].
AB  - PURPOSE: To investigate a method for determining antigen specific IgE antibodies
      in tears of patients with allergic keratoconjunctival disease. SUBJECTS AND
      METHODS: Antigen specific IgE antibodies to Japanese cedar pollen or Housedust
      Mites in tears of patients with allergic conjunctival diseases were examined.
      Both eyes in each patient were examined. The right eye was examined in normal
      healthy volunteers as a control. The number of eyes examined for IgE antibodies
      to Japanese ceder pollen was 32 eyes with seasonal allergic conjunctivitis(SAC),
      12 eyes with perennial allergic conjunctivitis(PAC), 12 eyes with atopic
      keratoconjunctivitis (AKC), 4 eyes with vernal keratoconjunctivitis (VKC), and 12
      eyes of the controls. The number of eyes examined for IgE antibodies to Housedust
      Mites was 32 eyes with SAC, 20 eyes with PAC, 30 eyes with AKC, 22 eyes with VKC,
      and 10 eyes with the control. Tears were sampled by the method of Schirmer Test
      1. Sampled tears were eluded with 200 microliters of phosphate buffered
      solution(pH 7.2, 0.05 M) and analyzed by the AlaSTAT-IMMULYZE method. Recovery
      rate of absorbance by filter paper for IgE antibodies in tears was determined by
      ratio to the standard sample of serum solution containing Housedust-Mite specific
      IgE antibodies with known concentration. RESULTS: Recovery rate of filter paper
      for IgE antibodies in tears was 83.6%. IgE antibodies in tears to Japanese cedar
      pollen were detected in 11 of 32 eyes of SAC. In other subjects, IgE antibodies
      were under the limit of the detection concentration except one eye of a patient
      with AKC. In the positive cases of Japanese cedar pollen specific IgE antibodies,
      there was no significant difference in the concentration between the right and
      the left eyes. IgE antibodies to Housedust-Mites were significantly higher not
      only in incidence but also in concentration in 18 of 22 eyes with VKC than in
      that in other in 8 of 20 eyes with PAC and 12 of 30 eyes with AKC. CONCLUSION:
      The method for determining antigen specific IgE antibodies in tears is clinically
      useful to diagnose and to investigate pathophysiology of allergic conjunctival
      diseases.

PMID- 14598710
TI  - [Vitrectomy for endophthalmitis after cataract surgery].
AB  - PURPOSE: To identify risk factors of poor visual outcome with vitrectomy for
      early-onset endophthalmitis after cataract surgery. PATIENTS AND METHODS:
      Clinical records of 29 consecutive eyes with endophthalmitis developing within 6
      weeks after cataract surgery and that underwent therapeutic vitrectomy between
      June 1996 and April 2001 were retrospectively reviewed. Twenty-two of the eyes
      received intravitreal injections of vancomycin and ceftazidime at the time of
      vitrectomy, and all patients received intravenous antibiotics. Eyes were divided
      into two groups; group A consisted of 22 eyes with a final visual acuity of 0.2
      or greater, and group B consisted of 7 eyes with a final visual acuity of less
      than 0.2. RESULTS: Fifteen eyes (52%) in group A achieved a visual acuity of 0.5
      or better and 8(28%) achieved a visual acuity of 1.0, while 4 eyes in group B
      developed phthisis bulbi. For eyes with a preoperative visual acuity of hand
      motions or worse, there was no correlation between final visual acuity and
      preoperative visual acuity. The overall culture-positive rate was 57%. In group
      A, methicillin-resistant Staphylococcus epidermidis was identified in 6 eyes,
      methicillin-resistant Staphylococcus aureus (MRSA) in 3 eyes and enterococcus in
      2 eyes. In group B, alpha-hemolytic streptococcus (AHS) was identified in 4 eyes,
      aspergillus in 1 eye, and MRSA in 1 eye. All isolates were sensitive to
      vancomycin with the exception of the aspergillus. AHS infection appeared to be
      associated with wound failure from the initial cataract surgery and a poor visual
      outcome. Among 3 of the eyes that developed phthisis bulbi, intravitreal
      injection of antibiotics was not performed. CONCLUSION: Early vitrectomy and
      intravitreal injection of vancomycin may improve visual outcomes, but infection
      with AHS may be associated with cataract surgery wound failure and poor visual
      outcomes.

PMID- 14598711
TI  - [Serial topographic changes at the optic disc in normal-tension glaucoma viewed
      with scanning laser tomography].
AB  - PURPOSE: To evaluate topographic changes in normal-tension glaucoma using serial
      optic disc images obtained by scanning laser tomography. SUBJECTS AND METHODS:
      Fifty-six eyes of 30 patients with normal-tension glaucoma were imaged using the
      Heidelberg Retina Tomography (HRT) four or more times during follow-up periods of
      more than 3 years. Disc progression was determined by regression analysis of
      global and segmental changes in optic disc parameters. Visual field progression
      was determined by Humphrey Field Analyzer (HFA) program 30-2 and was compared
      with disc progression. RESULTS: The global parameters of the optic disc showed
      progression in 21 of 56 eyes(37.5%). Progression was found in 30 eyes(53.6%) at
      the superotemporal segment, in 24 eyes(42.9%) at the temporal segment, in 27
      eyes(48.2%) at the inferotemporal segment, in 21 eyes(37.5%) at the superonasal
      segment, in 23 eyes(41.1%) at the nasal segment, and in 27 eyes(48.2%) at the
      inferonasal segment. The visual field showed progression in 19 eyes (33.9%). The
      progression in the optic disc parameters did not necessarily agree with that in
      the visual field. CONCLUSIONS: Glaucomatous disc changes over time can be
      determined with HRT using regression analysis.

PMID- 14598712
TI  - [Preferred retinal locus in patients with age-related macular degeneration].
AB  - PURPOSE: To evaluate the status and location of the preferred retinal locus(PRL)
      and visual function in age-related macular degeneration(AMD). SUBJECTS AND
      METHODS: Thirty-five patients were examined. They were diagnosed as having
      bilateral AMD in the disciform stage. Scanning laser ophthalmoscopic
      microperimetry was performed to detect the PRL. The retinal conditions of the PRL
      were classified using color fundus photographs and fluorescein angiography. The
      eccentricities of PRL from the fovea were measured. The relationships among
      visual acuity, retinal sensitivity, and the eccentricities of the PRL were
      evaluated. RESULTS: In 34 of 35 eyes, PRLs had shifted from an extrafoveal site
      and were located at the nearest foveal site on the healthy retina or on an
      atrophic lesion of the retinal pigment epithelium. When it was possible that
      other lesions were located where the PRL had shifted to, the PRL moved to the
      upper or temporal retina. The eccentricities of PRLs were 0.5-11 degrees. Visual
      acuities differed among the same retinal eccentricities. CONCLUSIONS: PRLs shift
      to the lesion nearest the fovea. These results suggest that visual acuity and
      retinal sensitivity are determined by the status of the PRL.

PMID- 14598713
TI  - [The effect of stellate ganglion block on prolonged post-operative ocular pain].
AB  - PURPOSE: There are cases when ocular pain persists long after ocular surgery and
      can not be reduced by anti-inflammatory drugs. Our purpose was to evaluate the
      effect of stellate ganglion block(SGB) on such prolonged post-operative ocular
      pain. METHOD: The subjects were 35 patients. Divided into two groups. One we
      called the nociceptive pain group, containing 29 cases in which the trigeminal
      nerve in the orbit or passing through it was intact. The other we called the
      neuropathic pain group, containing 6 cases in which pain accompanied paralysis of
      the trigeminal nerve. SGB was performed two times per week. SGB was deemed
      effective when pain was reduced markedly and the administration of anti
      inflammatory drugs became almost unnecessary. RESULTS: SGB was 96.6% effective in
      the nociceptive pain cases with the SGB performed an average of 5.9 times. On the
      other hand, in the neuropathic pain group, even though SGB was performed an
      average of 52.6 times it was only 66.7% effective. CONCLUSIONS: SGB may be useful
      for the treatment of prolonged post-operative ocular pain, but the elimination of
      neuropathic pain is more difficult than the elimination of nociceptive pain.

PMID- 14598714
TI  - [A case of optic nerve drusen associated with Gronblad-Strandberg syndrome].
AB  - PURPOSE: We report a rare case of optic nerve drusen associated with Gronblad
      Strandberg syndrome. CASE: The patient was a 29-year-old woman who had
      pseudoxanthoma elasticum on her neck. OBSERVATIONS: On eye examination, there
      were no abnormal findings in the anterior segment or ocular media.
      Ophthalmoscopic examination revealed milky white granular lesions on the optic
      nerve disc, and angioid streaks around the disc in both eyes. Orbital
      computerized tomography(CT), B-scan echography and photography with a fluorescein
      angiography filter identified the granular lesions as optic nerve drusen. With a
      scanning laser ophthalmoscope(SLO), poorly-visible drusen buried below the nerve
      head could be detected. The optic nerve drusen could be seen more clearly by
      infrared laser than by helium-neon laser. CONCLUSIONS: SLO using infrared laser
      is useful for evaluation of superficial and buried drusen.

PMID- 14598715
TI  - [A review 16. Laser therapy of eyes].

PMID- 14598716
TI  - [Usefulness of technetium-99m tetrofosmin single-photon emission computed
      tomography for short-term risk stratification in patients with acute chest pain
      in the emergency room].
AB  - OBJECTIVES: High-risk patients with acute coronary syndrome are difficult to
      distinguish from low-risk patients with chest pain in the emergency room.
      Technetium-99m (99mTc) tetrofosmin single-photon emission computed tomography
      (SPECT) was investigated to exclude high-risk patients with chest pain in the
      emergency room. METHODS: 99mTc-tetrofosmin SPECT was evaluated using a four-point
      scoring system in 228 patients (144 men, 84 women, mean age 68 +/- 12 years) with
      chest pain. Negative was defined as the myocardial segments with a defect score
      (DS) of < 2. The patients were divided into two groups; the negative group with
      DS < 2 (n = 78) and the positive group with DS > or = 2 (n = 150). Cardiac events
      (cardiac death, acute myocardial infarction and refractory angina) were evaluated
      within 30 days of onset. ST-segment elevation or depression > or = 0.1 mV was
      defined as positive in electrocardiography. The results of SPECT were compared
      with those of electrocardiography, transthoracic echocardiography and serum
      cardiac markers (troponin T and creatine kinase-MB) in 95 patients. RESULTS: The
      negative group had very few cardiac events (three patients with refractory
      angina) (3.8%). The negative predictive value of cardiac events evaluated by
      electrocardiography was calculated as 83.1%, whereas the negative predictive
      value by SPECT was 96.2% (p < 0.01). In addition, the negative predictive value
      of acute myocardial infarction by SPECT was 100%. The negative predictive values
      of cardiac events evaluated by SPECT, electrocardiography, transthoracic
      echocardiography and serum cardiac markers were 95.8%, 81.5% (vs 99mTc
      tetrofosmin; NS), 84.9% (NS) and 60.4% (p < 0.05), respectively. CONCLUSIONS:
      99mTc-tetrofosmin SPECT is a useful method to exclude high-risk patients among
      patients with chest pain in the emergency room.

PMID- 14598717
TI  - [Development of measure for disease-specific quality of life in patients with
      chronic heart failure].
AB  - OBJECTIVES: To develop a measure for disease-specific health-related quality of
      life in patients with heart failure and examine its reliability and validity.
      METHODS: One hundred and four patients with stable chronic heart failure (74
      males, 30 females, mean age 64.2 +/- 10.0 years) with left ventricular ejection
      fractions of less than 40% were enrolled in this study. Each patient responded to
      the Medical Outcomes Study Short Form 36 (SF-36) and a disease specific
      questionnaire comprising four categories (dyspnea, sleep, appetite and fatigue),
      each consisting of five to six questions. A stepwise exploratory factor analysis
      was applied to the disease-specific measure to consider categorical fitness. In
      25 of the 104 patients, the data in the questionnaire were compared with peak
      oxygen uptake, anaerobic threshold, slope of the regression line relating the
      ventilatory equivalent to carbon dioxide output (VE/VCO2 slope) and peak work
      rate. Correlations between the questionnaire and eight components of SF-36 were
      evaluated. RESULTS: The appetite category proved unreliable and was excluded from
      consideration, so 12 questions were adopted from the other three categories.
      Cronbach's a values ranged from 0.68 to 0.89 and the coefficients of test-retest
      were from 0.84 to 0.94, so both internal consistency and reproducibility of these
      questions were considered excellent. The scores of three categories well
      reflected the severity of heart failure based in New York Heart Association
      functional class. The anaerobic threshold (r = 0.53), peak oxygen uptake (r =
      0.66), VE/VCO2 slope (r = -0.48) and peak work rate (r = 0.41) correlated with
      the total score of the 12 questions. The total scores were closely correlated
      with the eight components of SF-36. CONCLUSIONS: This study suggests that the
      disease-specific questionnaire is applicable to evaluation of the health-related
      quality of life in patients with heart failure.

PMID- 14598718
TI  - Prognostic significance of post-exercise blood pressure response in patients with
      dilated cardiomyopathy.
AB  - BACKGROUND AND OBJECTIVES: The occurrence of an abnormal cardiovascular response
      during exercise in patients with chronic heart failure is well known. Post
      exercise blood pressure response is also useful in assessing the severity of
      heart failure and impaired exercise capacity. This study evaluated the prognostic
      significance of post-exercise blood pressure response in patients with dilated
      cardiomyopathy. METHODS: Thirty patients with dilated cardiomyopathy (left
      ventricular ejection fraction: 32 +/- 9%) were studied and the relationship
      between post-exercise blood pressure response and cardiac events (sudden death,
      heart failure death and readmission for heart failure) were evaluated. The post
      exercise blood pressure response was defined as PBP3 (systolic blood pressure at
      3 min after exercise divided by peak systolic blood pressure during exercise).
      RESULTS: Seven cardiac events (one sudden death, two deaths for heart failure and
      four readmissions from heart failure) were observed during the follow-up period
      (3.3 +/- 1.8 years). The PBP3 in patients with these cardiac events was higher
      than that in patients without cardiac events (0.95 +/- 0.09 vs 0.84 +/- 0.10, p <
      0.05). The area under the curve for the receiver-operating characteristic curve
      with PBP3 used to predict the cardiovascular events was 0.79 (95% confidence
      interval: 0.62-0.97, p = 0.02). CONCLUSIONS: Post-exercise blood pressure
      response is a simple and useful predictor of adverse cardiac events in patients
      with dilated cardiomyopathy.

PMID- 14598719
TI  - [Validation of a new hand-carried ultrasound device equipped with directional
      color power Doppler and continuous wave Doppler].
AB  - OBJECTIVES: This study evaluated the accuracy of the directional color power
      Doppler (DCPD) and continuous wave Doppler (CWD) methods incorporated in the new
      hand-carried SonoSite 180PLUS ultrasound device. METHODS: The hand-held
      ultrasound system with 2.5 MHz transducer and SONOS 5500 was used as a standard
      ultrasound system with a 2 to 4 MHz wideband transducer. The experimental study
      used a Doppler wire phantom to evaluate the influence of target wire speed and
      angle of transducer on DCPD imaging. The clinical study included 48 consecutive
      patients. DCPD assessment of valvular regurgitation measured the distances of
      DCPD signals of mitral, aortic and tricuspid valve regurgitation using the apical
      four-chamber view for comparison with standard echocardiography. CWD assessment
      measured the peak velocities of the aortic flow and tricuspid valve regurgitant
      flow for comparison with standard echocardiography. RESULTS: In the experimental
      study, DCPD signals were not influenced by target wire speed changes and
      transducer incident angles. In the clinical study, agreements for mitral, aortic
      and tricuspid regurgitation between the two methods were 89.6%, 81.8% and 78.7%,
      respectively. The distances of DCPD valve regurgitant signals by the hand-carried
      ultrasound device showed good correlation (mitral regurgitation: y = 0.84x +
      0.55; r = 0.93, aortic regurgitation: y = 0.95x + 0.27; r = 0.94, tricuspid
      regurgitation: y = 0.86x + 0.61; r = 0.90) with those by standard
      echocardiography. Evaluation of CWD velocity measurements showed good agreement
      for the lower flow velocities (< 2.0 m/sec). However, underestimation occurred
      for the high flow velocities (> 2.0 m/sec) compared with those by standard
      echocardiography (aortic flow: y = 0.80x + 0.11; r = 0.95, tricuspid
      regurgitation: y = 1.00x - 0.23; r = 0.90). CONCLUSIONS: The new hand-carried
      ultrasound device (SonoSite 180PLUS equipped with DCPD and CWD) is clinically
      useful for evaluating valvular regurgitations and flow velocities. Further
      studies are needed to determine the mechanism of the underestimation of high flow
      velocities by CWD.

PMID- 14598720
TI  - [Ampulla cardiomyopathy with delayed recovery of microvascular stunning: a case
      report].
AB  - A 71-year old woman with schizophrenia was admitted to our hospital on November
      26, 2002 under a diagnosis of acute myocardial infarction because of ST segment
      elevation in leads V2-V5 and positive serum cardiac troponin T level. Emergent
      coronary angiography showed no significant stenosis, but left ventriculography
      demonstrated apical ballooning and basal hyperkinesis. The final diagnosis was
      ampulla cardiomyopathy. Myocardial contrast echocardiography during the acute
      phase revealed an echocontrast defect consistent with the area of apical
      ballooning. The condition improved gradually as determined by disappearance of
      the abnormal wall motion. The coronary flow reserve in the left anterior
      descending artery measured by transthoracic Doppler echocardiography was
      decreased at 1.5 in the acute phase and gradually recovered over a period of 3
      months (23 days, 1.9; 96 days, 2.9). Microvascular stunning defined as decreased
      coronary flow reserve was observed and recovery was delayed in this case compared
      with cases of myocardial stunning. These findings are of interest in evaluating
      the pathophysiology of ampulla cardiomyopathy.

PMID- 14598721
TI  - [A 57-year-old woman with a new diastolic murmur after aortic valve replacement.
      Prosthetic aortic valve detachment].

PMID- 14598722
TI  - Maxwell's legacy.

PMID- 14598724
TI  - Microwave techniques in agriculture.
AB  - Microwave techniques, methods and instrumentation can be utilized in agriculture
      to improve the efficiency of crop production, handling and processing, and
      improve the quality of products. Pertinent microwave theory relative to such
      applications is discussed, and a review of microwave research on agricultural
      problems is presented. A wide range of applications is treated briefly, including
      examples of successful applications of microwaves in agriculture, and some future
      prospects are discussed.

PMID- 14598726
TI  - A review of microwave-assisted polymer chemistry (MAPC).
AB  - As a relatively new source of processing energy, microwave energy offers many
      compelling advantages in materials processing over conventional heat sources.
      These advantages include greater flexibility, greater speed and energy savings,
      improved product quality and properties, and synthesis of new materials that
      cannot be produced by other heating methods. Studies of microwave processing of
      polymeric materials in the early 1960s led to a successful industrial application
      in the rubber industry. Since the mid-1980's, there has been a great deal of
      interest in microwave processing of polymeric materials worldwide. The discipline
      can be categorized in two major fields: microwave-assisted polymer physics (MAPP)
      and microwave assisted polymer chemistry (MAPC). This paper offers an overview of
      the state-of-the-art research on the field of MAPC, including polymer processing
      (curing of thermosets, processing of thermoplastics, and joining), polymer
      synthesis, plasma modification of polymer surfaces, plasma polymerization,
      polymer degradation, and production of nanomaterials. Most of these studies have
      focused on laboratory-scale, exploratory efforts. Challenges and possible future
      directions for the commercialization of microwave processing technologies are
      discussed.

PMID- 14598728
TI  - [Priority fundamental research of the integrated nervous system activity].

PMID- 14598729
TI  - [Priority clinical research in neurology].

PMID- 14598730
TI  - [Outlining of the fundamentals for optimizing the antimicrobial therapy of
      suppurative-inflammatory diseases].
AB  - The inflammatory cascade was proven to be triggered rather by small structures of
      the bacterial origin, i.e. chemical components of bacterial cells, than by
      bacteria themselves. Sepsis can be viewed today as a body response to an extreme
      microbe load caused not so much by the circulation of live microorganisms in the
      blood but rather by an excessive penetration of structural components and
      molecules of the microbe origin into the blood. Studies of microorganisms' signal
      molecules are still at the laboratory research stage, however, it can be forecast
      today that the above studies are clinically prospective. It is actually in case
      of infections provoked by opportunistically pathogenic microorganisms that the
      key task consists not in the elimination of bacteria but in the normalization of
      the host-microbe relations; the possibility to decipher the conduct of microbes
      through understanding the molecules' signals will provide a clue to comprehending
      and regulating such most important etiological-and-pathogenetic mechanisms as
      adhesions, pathological colonization, metabolic activity, bacterial super-growth
      etc. The confirmed ability of volatile fatty acids (end-products of anaerobic
      bacteria) to suppress the inflammatory reaction of macrophages urges further
      search for microbe metabolites with the anti-inflammatory activity. The gas
      chromatography and mass-spectrometry investigations, implemented in the mode of
      mass-fragment scanning, provide for determining (in the blood and other human
      fluids) dozens of molecules of the microbe origin, which are not synthesized by
      human cells but which are typical of certain types of microorganisms. It is
      suggested to carry on with a number of prospective trends based on using the
      express-tests or so-called non-cultivative diagnostics; such trends are also
      related with defining the metabolic activity of microorganisms according to a
      level of their end-product in the blood serum of patients, and with monitoring
      the level of the microbe load according to chemical components and signal
      bacteria in biological fluids etc. Finally, all of them are targeted at
      optimizing the antibiotic therapy.

PMID- 14598731
TI  - [Comparative morpho-functional assessment of the impact produced by prolonged
      infusions of prostaglandins E and F on the course of genetically preconditioned
      arterial hypertension].
AB  - The administration of prolonged intravenous infusions of prostaglandins is
      defined; the method provided for specifying a long-term impact produced by
      prostaglandins on a nature of the course of genetically preconditioned arterial
      hypertension (AHT) in rats. Infusions of PGE-2 bring about a prolonged and stable
      reduction of mean arterial presser (AP) by 10% versus its original value; they
      intensify 2-fold the depressor baroreflectory regulation and stimulate the
      urinary excretion of endogenous renal PGF-2 alpha; besides, they contribute to a
      better blood supply to organs, i.e. an increased perfusion of the cortical and
      medullary layers of the kidneys and of the brain substances; and dilatation of
      the intramural branches of the coronary arteries, due to which the AP becomes
      milder. Infusions of PGF-2 alpha contribute to a prolonged and stable elevation
      of mean AP by 12% versus the original value; they inhibit the depressor
      baroreflectory regulation and intensify the pressor baroreflectory regulation;
      they, additionally, induce the urinary excretion of endogenous renal PGF-2 alpha
      and correct the lesions in the blood supply to organs, i.e. pathological
      microcirculation, anemia and spasm of the renal parenchyma, ischemic foci in the
      myocardium, spastic contraction of small cerebral arteries, edema and destructive
      changes (of the local necrosis variation) in the cerebral substance microvessels
      concomitant with a commencing diapedetic hemorrhages. Finally, all above listed
      lesions are signs of the malignant AP course.

PMID- 14598732
TI  - [Biomechanical studies in present-day ophthalmology].
AB  - The human eye is a unique physiological system, in which the major part of
      structural elements obeys the general laws and regularities of biomechanics. The
      article offers an analytical review of research and development projects in the
      field of eye biomechanics accomplished in Russia and other countries over the
      last five years. The below eight directions of biomechanical studies have been
      found rapidly progressing in ophthalmology: biomechanics of the cornea;
      biomechanics of the corneoscleral capsule; biomechanics of the crystalline lens;
      biomechanics of accommodation; biomechanics of glaucoma; biomechanical modeling
      of retinal, choroidal and vitreous body detachment; biomechanics of eye injury
      and oculomotor biomechanics. The importance of biomechanical methods for the
      study of pathogenesis of various eye disease and for their targeted treatment was
      demonstrated. New ophthalmological tasks were set which may benefit a lot from
      the biomechanical ideas and methods applied to them.

PMID- 14598733
TI  - [The role of the components of the renin-angiotensin system in the ocular tissues
      in norm and pathology].
AB  - Different components of the renin-angiotensin system (RAS), whose content and
      activity are predetermined by local factors, are generated in the ocular tissue
      structures. The local eye RAS plays an important role in pathogenesis of
      different eye diseases and in the local manifestations of general pathological
      processes. Therefore, a study of the eye RAS components in norm and in disease
      contributes to understanding the pathogenesis of eye diseases and opens up new
      possibilities for an adequate treatment. The RAS components in the lacrimal fluid
      can be an important characteristics of such diseases like keratitis, diabetic
      retinopathy etc.

PMID- 14598734
TI  - [Xenon effects on cells and receptors].
AB  - Xenon (Xe) is being more widely used in medicine owing to its unique physical-and
      chemical properties of a noble gas. However, the knowledge about the
      physiological and patho-physiological changes occurring in the organism and in
      its separate structures during the interaction with Xe is still scanty. The aim
      of this survey was to briefly describe the presently known Xe biological-and
      medical properties and certain mechanisms of Xe impact produced on cells and
      receptors as well as on the release of mediators and hormones. Besides, the Xe
      hemodynamic effects are also defined. The conclusion is that the Xe effect can be
      of a complex nature and can depend on the conditions of the body vital activity
      (optimal condition, activation, lesion), which predetermine, in their turn, the
      performance of the structural-and-functional units of various cellular systems.

PMID- 14598735
TI  - [Polymerase chain reaction in the diagnosis of viral infections in the newborn].
AB  - Two hundred and ten newborns from among a high risk group were examined for
      intrauterine infections by polymerase chain reaction (PCR) with the aim of
      assessing the clinical information density of the method in the diagnostic
      sphere. The patients were examined for the presence of DNA/RNA viruses and
      bacteria. Genetic samples of various causative agents were detected in 49% of the
      newborns. No correlation was established between the clinical pattern and the
      presence of DNA of certain microorganisms. The most severe condition of newborns
      was noted in cases when a DNA causative agent was found in several different
      biological samples. The highest mortality (in per cent) was registered in the
      group of newborns with detected DNA of Herpesviridae viruses. The PCR clinical
      value was affirmed for establishing a disease etiology in newborns.

PMID- 14598736
TI  - [Laser fluorescence in assessing the hygienic status of oral cavity].
AB  - The issue related with an objective evaluation of a hygienic status of the oral
      cavity and a method to solve it by modern laser technologies are addressed in the
      paper. The efficiency of bacteriological and of laser-fluorescence express
      diagnostics is comparatively analyzed. A hygienic index and its clinical value
      are substantiated.

PMID- 14598737
TI  - [Cytokines and other signal molecules in the pathogenesis of acute pancreatitis].

PMID- 14598739
TI  - [Practice of the application of the Federal Law "On the Population's Sanitary and
      Epidemiological Wellbeing" and of improving the sanitary legislation].

PMID- 14598738
TI  - [Normal microflora of the genital tract in healthy women of the reproductive
      age].

PMID- 14598740
TI  - [The sanitary status of natural waters on the territory of Moscow (according to
      the results of the examination of chemical and radionuclide composition)].
AB  - The paper presents the results of examination of the chemical and radionuclide
      composition of natural waters and snow cover in Moscow. Areas with abnormal
      contents of tritium are found in the underground and surface waters and snow
      cover. The high concentrations of strontium, boron, fluorine, and barium are
      ascertained to be associated with natural factors. Areas of technogenically
      polluted underground waters are identified. Recommendations are given for further
      studies. Particular emphasis is laid on that the artesian wells that are a
      reservoir source of water supply under emergency are to be revised.

PMID- 14598741
TI  - [Railway use of asbestos-containing rubble: environmental hygienic aspects].
AB  - The paper presents the results of a study of the gravimetric and counting
      concentrations of respirable asbestos fibers while working with sand-and-crushed
      stone mixtures, obtained from the concentration of chrysotile asbestos, at
      distances of 25, 50, and 100 m from the working place, as well as in a car saloon
      when the electric train passes along the area of these operations following an
      hour, a day, and a year after the completion of work, in warm and colds seasons
      of a year. It is concluded that the use of asbestos-containing sand-and-crushed
      stone mixtures on the railway leads to a higher anthropogenic asbestos load on
      the population living in the railway right-of-way, on railway workers and
      passengers. In this connection, it is necessary to evaluate risk factors of
      asbestos-induced diseases among the above contingents. The authors consider that
      due to the fact that asbestos-containing sand-and-crushed stone mixtures are well
      wetted with water, followed by the formation of a firm surface crust that
      prevents dust formation, as well as the short duration and rare frequency of
      operations relating their change, it is necessary to irrigate the repair areas
      with water or surfactant liquids after work termination.

PMID- 14598742
TI  - [Risk of the incidence of urinary tract diseases in industrial centers of the
      Maritime Territory].
AB  - The study was undertaken to establish whether there is a relationship of the
      incidence of urinary diseases (UD) in the population of industrial towns in the
      Primorye Territory to the water basin. This evaluation was based on the
      principles of calculation and on the analysis of epidemiological and ecological
      risks. The environment in the Primorye Territory was found to be dangerous to
      human health and to affect the spread of UD; with varying social and natural
      conditions, specific features and amounts of discharged pollutants, the
      ecological risk exceeds the epidemiological one; there is a high association of
      the incidence of UD in the port towns and industrial centers where the
      enterprises of coal mining, chemical, and non-ferrous metallurgic industries are
      located.

PMID- 14598743
TI  - [Content of trace elements in the bottoms of open water reservoirs in the Western
      part of the Orenburg Region].
AB  - The mean concentrations of trace elements were determined in the bottoms of open
      water reservoirs in the western part of the Orenburg Region. The content of
      chromium was found to exceed the maximum permissible concentration by about 5
      times, that of zinc and nickel complies with the clarke; that of copper was
      nearly 2 times less than the clarke, that of cobalt and vanadium is nearly 1.5
      times less. The concentrations of trace elements in the bottoms were compared
      with those in soil, portable water, and snow cover in order to elucidate possible
      sources of origin.

PMID- 14598744
TI  - [Accumulation of toxic types of microscopic fungi in urban soils].
AB  - It has found that the structure of a complex of chernozem micromycetes was
      altered; the greatest impairments of the microflora were near busy urban
      highways. There was a significant rise and abundance of toxic, opportunistic,
      allergenic micromycetes. It is necessary to monitor the content of opportunistic
      types of fungi and the accumulation of mycotoxins in agricultural products in
      urban areas due to a greater threat to the urban population.

PMID- 14598745
TI  - [Threats to human health in the use of pesticides (a review)].
AB  - The paper presents current trends in the use of pesticides and detection of their
      residues in the environmental objects. Pesticides are shown to be a serious
      health risk factor for different groups of the population when they are
      irrationally used and inadequately stored. A package of measures to prevent
      intoxication and to reduce a risk for pesticide entry into the body is provided.

PMID- 14598746
TI  - [Sanitary monitoring of the procedure of cleaning hopper cars after carriage of
      mineral fertilizers: ecological and hygienic aspects].
AB  - The paper presents the results of field tests of a hopper wagon after carriage of
      mineral fertilizers, which are further to be used for grain carriage. The tests
      were carried out step by steps: washings from the inner surface of the hopper
      wagon after carriage of mineral fertilizers in order to identify chemical
      substances and 12 hours after its abrasive sandblasting; washings from the inner
      surface, air sampling for filters and into absorbable solutions after completion
      of wagon blowing 2 hours after dust removal and 30 days after application of an
      Epovin enamel. It has been concluded that most ions as components of mineral
      fertilizers were found in the amounts greater than the maximum acceptable
      concentrations on the walls and inside the hopper wagon after mechanical cleaning
      of its inner surface of the wagon that carries minerals, as well as its
      subsequent abrasive sandblasting and blowing.

PMID- 14598747
TI  - [Comparative assessment of the clastogenic potential of various industrial
      enterprises].
AB  - The paper comparatively assesses the level and qualitative spectrum of
      chromosomal aberrations (CA) in 192 workers engaged in 3 industries (cake and by
      product, aluminum, and mining concentration processes). The maximum and minimum
      rates (6.43(+)-0.32% and 3.81(+)-0.46%) of CA have been observed in those engaged
      in cake and by-product and mining concentration processes, respectively. The
      combined influence of chemical and radiation factors are a cause of the higher
      rate of CA. Gender- and age-specific features do not effect on the level of
      structural CA. Smoking is a factor of their slight modification as there are no
      significant differences in the frequencies of aberrations between smokers and non
      smokers in any professional group. There is an indirect relationship between the
      frequency of CA and the length of service, which may be different under the
      conditions of various industries.

PMID- 14598748
TI  - [Immunological criteria of development of silicotuberculosis].

PMID- 14598749
TI  - [Present-day sociomedical problems of orphans].
AB  - The specific features of physical and mental development, health status, and
      lifestyle were found in orphans of sensitive age under the present socioeconomic
      conditions. The specific features of the adaptive capacities were first studied
      in these children. Abnormalities in the physical development and health status of
      orphans were shown to form under their institutional conditions of life,
      nutrition, and education, and upbringing. Guidelines for medical workers of
      orphan's institutions and for workers of sanitary-and-epidemiological service are
      substantiated.

PMID- 14598750
TI  - [Immunity status of children under the conditions of heavy metal-polluted city].
AB  - This study assessed immunological changes in apparently healthy children under a
      slight (less than the sanitary standards) urban pollution with heavy metals (Co,
      Pb, Cr, Cd, Mn, Ni, Zn, and Cu). Their pollution of the urban environment was
      determined with the contamination of snow cover and ambient air in Kazan. With
      low levels of ambient air pollution with heavy metals, monitoring the level of
      environmental pollution is an adequate method for evaluating the urban area,
      which allows the latter to be ranged by the degree of pollution. Apparently
      healthy children who live under relatively good environmental conditions are at
      risk for allergic and autoimmune diseases or secondary immunological somatic
      pathology.

PMID- 14598751
TI  - [Organization of an educational process and routine for senior lyceum students].
AB  - The paper presents the data of a comparative analysis of the specific features of
      an educational process and the routine for senior pupils of biochemical lyceums
      and those of secondary educational schools. The organization of an educational
      process in the senior forms of biochemical lyceums is not optimal and, which is
      more, health-promoting. Good training for entering a higher educational
      establishment is a high "physiological price": not getting enough sleep,
      insufficient being in fresh air, no spare time, and mental and emotional stress.
      This contingent is certain to require more control of their health status, the
      conditions and organization of schooling, and active measures aimed at their
      improvement and optimization.

PMID- 14598752
TI  - [Comparative analysis of morbidity among gymnasium and general educational school
      students].
AB  - Gymnasiums and general educational schools have most widely spread in Kazan now.
      By the end of schooling, the difference in the prevalence of all diseases in the
      gymnasium and school is 244.22 and 908.11, respectively, i.e. this figure is 3.7
      times higher in the general educational school than that in the gymnasium. In the
      school-leaving forms of a general educational school, the prevalence of different
      abnormalities is twice higher than in those of gymnasium. Thus, there has been a
      2.2-fold decrease in the proportion of apparently healthy children in the past 5
      years. In the school-leaving pupils of a general educational school, the
      prevalence of abnormalities is twice higher than that in gymnasium pupils of the
      same age and a 13-fold rise in the prevalence of mental disease exacts a very
      careful attention.

PMID- 14598753
TI  - [Impact of the type of feeding on children's physical development].
AB  - Physical development was comparatively assessed in 1238 children of the first
      year of life who were differently fed. The children living in both the town of
      Kirov and rural areas of the Kirov Region who were on artificial feeding showed
      higher weight and height values, but they developed less harmonically than those
      of the same age who were fed with breast milk.

PMID- 14598754
TI  - [Influence of school environmental factors and learning on pupils' health].
AB  - This study is a part of a comprehensive research conducted at 10 schools of
      different education types (general educational school, specialized gymnasiums,
      language schools, colleges, lyceums) that are situated in Sofia. A relationship
      between the factors that characterize school and the training environment, and
      the health status of pupils was established by using currently available
      statistical methods. The findings show that the discrepancy between the school
      and training environment and the sanitary requirements and standards affect both
      the general and school age-specific morbidity rates in pupils. Knowing the
      factors, which characterize school in accordance with the claimed educational
      goals, and schooling factors enables one to arrange all schools.

PMID- 14598755
TI  - [Adolescents' health in Nagorno-Karabakh].
AB  - Some health indices were studied in teenagers in Nagorny Karabakh. The paper
      presents data on their physical development, hemodynamics, sexual maturity, and
      total morbidity. There are some regional features in the study indices, which
      consist in low harmonicity of physical development and hemodynamics, as well as
      in high morbidity rates with a predominance of cardiovascular and collagen
      diseases. The found abnormalities may be directly related to the poor environment
      for teenagers in Nagorny Karabakh after the 1991-1994 war in the region and show
      it necessary to improve their living conditions, medical control, and
      therapeutical-and-prophylactic measures.

PMID- 14598756
TI  - [Monitoring body's functional capacities in school children].

PMID- 14598757
TI  - [Regulation of the metabolism of ethyl alcohol in the body with oligomeric
      proanthocyanides as a preventive measure against its toxic effect].
AB  - The study evaluated the effects of a complex of oligomer proanthocyanidines
      derived from the crowns of the grapes Vitis vinifera on the oxidation of ethanol
      and on the activity of alcohol dehydrogenase and aldehyde dehydrogenase in the
      plasma of male volunteers given ethanol once, as well as in the rat liver during
      long-term alcohol use. Oligomer proanthocyanides were shown to be actively
      involved in the human and animal metabolism of ethyl alcohol in vivo. Under their
      action, the reductase activity was preserved, which prevented acetaldehyde from
      accumulating in the body since it reduces to less toxic ethanol. Oligomer
      proanthocyanidines from the crowns of the grape may be used to prevent a
      significant toxic effect of excess doses of ethyl alcohol on the body.

PMID- 14598758
TI  - [Benzimidazole derivative inhibition of the mutagenic activity of 2
      aminoanthracene].
AB  - The antimutagenic activity of a new benzimidazole derivative that has
      antioxidative properties was found in the Salmonella/microsome test. This
      compound reduced the level histidine revertants induced by the promutagen and
      carcinogen 2-aminoanthracene. Inhibition of the mutagenicity of 2-aminoanthracene
      appears to be associated with the inactivation of its genotoxic metabolites. The
      capacity of the benzimidazole derivative for antimutagenic effects is possibly
      due to a dihydroxyphenyl radical that is present in its structure.

PMID- 14598759
TI  - [Formation of sanitary and epidemiological services under market economy in
      Moscow].

PMID- 14598760
TI  - [X-ray diagnosis in the railway therapeutical and prophylactic institutions:
      state of the art and trends].

PMID- 14598761
TI  - [Main problems and tasks of integration of the activity of a district state
      sanitary-and-epidemiological surveillance facility].

PMID- 14598762
TI  - [Determination of environmental pollution by the results of study of snow cover].

PMID- 14598763
TI  - [Optimization of microbiological air monitoring in hospital premises].

PMID- 14598764
TI  - [Asymmetrical dimethylhydrazine in the environment: problems of monitoring and
      ways of their solution].

PMID- 14598765
TI  - Progress in data collection improves alignment but adds new challenges.
AB  - A relatively small percentage of hospitals have fully integrated systems. The
      term "completeness of record" takes on entirely new meaning. Vendors play
      critical role in the new world of electronic data capture.

PMID- 14598766
TI  - East-west synthesis drives change model.
AB  - Each team is given six weeks to complete a change project. For effective change
      to occur, the entire staff must undergo the process. The pharmacy, information
      line, and diagnostic center are initial target areas.

PMID- 14598767
TI  - Stroke centers can cut LOS, boost outcomes.
AB  - The center is not so much a place as an organized response system. Team meets in
      hospital on regular basis to discuss patient progress. Pathway for acute stroke
      care is an essential ingredient in the formula for success.

PMID- 14598768
TI  - CAM a special challenge for cardiac care.
AB  - Some patients are driven to complementary and alternative medicine because
      traditional medicine offers no cure. Patients and some physicians may be unaware
      of potential contraindications. Bleeding is one of the primary concerns in
      patients using both modalities.

PMID- 14598769
TI  - Collaborative patient safety program launched.
AB  - Root-cause analysis of adverse events and near misses are emphasized. Participant
      make-up offers opportunity to hear differing viewpoints. VA Center for Patient
      Safety considered a leader in safety movement.

PMID- 14598770
TI  - [Imitative models of the organization of treatment and evacuation measures
      conducted in the infantry regiment during combat].
AB  - During the combat the chief of medical service has to solve both the direct
      mission, i.e. to choose the most effective variant of organization of treatment
      and-evacuation measures (TEM) and the indirect one, i.e. to define the needs of
      medical service in forces and resources according to the given model. To fulfill
      these missions the most effective method is the multi-criteria approach for
      practical realization of which the "successive steps" method was chosen. The main
      indicator of TEM effectiveness is the time from the wounding to the point of
      readiness for evacuation from the regimental aid station. The GPSS language of
      different dialects as the modelling environment is preferred on the basis of
      which two computerized imitative models were created: the model of TEM
      effectiveness in the company-battalion link and the model of regimental aid
      station work.

PMID- 14598771
TI  - [The name of the medical services department of organization and tactics of the
      Military Medical Academy].

PMID- 14598772
TI  - [The work of the field multipurpose hospital intended for rendering medical care
      to surgical casualties in the Northern Caucasus].

PMID- 14598773
TI  - [Optimization of sepsis therapy (literature review)].

PMID- 14598774
TI  - [Evaluation of immunologic disorders in patients suffering from diffuse
      peritonitis].

PMID- 14598775
TI  - [Use of phenomenon of adsorption decrease in solid cohesion for remote
      lithotripsy (experimental study)].
AB  - The possibility of using the phenomenon of adsorption decrease in solid cohesion
      well known in the colloid chemistry as Rebinder effect for nephrolith remote
      destruction was studied. Sorption properties of urine components in healthy
      persons and those suffering from urolithiasis were compared. The number of
      synthetic surfactants were studied according to the values of bordering
      moistening angle and efficiency of remote destruction of firm nephrolithes in
      vitro. The bordering moistening angle measurements have shown that the urine of
      healthy persons demonstrates higher surface activity compared with the urine of
      those suffering from urolithiasis. The correlation between the value of bordering
      moistening angle for the liquid into which the urolithiasis was immersed and the
      destruction efficiency in vitro in that media was established. The efficiency of
      nephrolith destruction was found to increase in the water solution of
      chlorhexidine bigluconate.

PMID- 14598776
TI  - [Cardiopathy in infectious diseases: clinical and pathogenetic aspects of
      diagnosis].
AB  - The disease of cardiovascular system is one of the causes of invalidity and
      unfavorable outcomes. Together with such common diseases as rheumatism,
      hypertension, atherosclerosis that cause the development of cardiovascular
      insufficiency there are many other diseases including the infectious one that
      have rather unfavorable influence on the myocardium and vascular system. The
      disorders in cardiovascular functions at acute infectious diseases are noted
      frequently (80%) and closely connected with total pathogenesis of the disease.
      They influence the clinical course and outcomes of infectious process. Follow-up
      of the infectious patients and conduction of rational and especially intensive
      therapy require the wide functional control of cardiovascular state at different
      stages of the disease. The work shows our great experience in development of the
      problem of clinical-and-electrocardiographic investigations in infectious
      patients. The critical analysis of the problem condition today according to the
      literature data is presented. The material is based on the investigation of about
      25 thousand patients treated in the clinic of infectious diseases of the Military
      Medical Academy for the last 30 years.

PMID- 14598777
TI  - [Armored medical vehicles of the medical service troop link of the Russian
      Federation Armed Forces].

PMID- 14598778
TI  - [Legal basis of medical examinations of servicemen and personnel discharged from
      the Russian Federation Armed Forces].

PMID- 14598779
TI  - [Guarding the health of servicemen].

PMID- 14598780
TI  - [From the history of the Siberian Military District State Sanitary Epidemiologic
      Inspection Center].

PMID- 14598781
TI  - [The Leningrad military health center].

PMID- 14598782
TI  - [Tverskoy military hospital--70 years].

PMID- 14598783
TI  - [Formation and development of the neurological service in the Burdenko Main
      Military Clinical Hospital].

PMID- 14598784
TI  - HIV epidemics, HIV therapeutics: recent trends.

PMID- 14598785
TI  - Revised guidelines will ease selection of HIV/AIDS treatments.

PMID- 14598786
TI  - Scientists document increasing reports of HIV superinfection.

PMID- 14598787
TI  - Study raises possibility of safer breast-feeding for infants of mothers with HIV
      infection.

PMID- 14598788
TI  - HIV and outcomes measurement: quantitating performance.

PMID- 14598789
TI  - Boosted PIs: competition hots up.

PMID- 14598790
TI  - Drug interactions associated with HAART: focus on treatments for addiction and
      recreational drugs.
AB  - The advent of HAART has improved survival in patients infected with HIV; however,
      treatment is complicated by potential drug interactions. The risk of drug
      interactions is compounded by the use of additional therapies for comorbid
      conditions, such as substance abuse, and by the use of recreational drugs. HIV
      health care providers should be aware of the potential interaction of
      recreational drugs and addiction treatments with HAART because of the potential
      for significant adverse effects for their HIV-infected patients. This article
      provides a review of the literature on drug interactions among addiction
      therapies, recreational drugs, and HAART.

PMID- 14598791
TI  - Editorial comment: does this drug make the patient better or worse? Interactions
      between pharmacists and members of the health care team.

PMID- 14598792
TI  - BMP4 promotes chondrocyte proliferation and hypertrophy in the endochondral
      cranial base.
AB  - Defects in the growth and development of the endochondral bones that comprise the
      cranial base contribute to several craniofacial dysmorphic syndromes. Since Bone
      Morphogenetic Protein (BMP) signaling regulates chondrocyte differentiation and
      endochondral ossification in developing long bones, we have tested the hypothesis
      that BMP signaling also participates in regulating development of the cranial
      base. During in vivo developmental progression of the cranial base in mice, a
      burst of skeletal growth and chondrocyte maturation was identified in the
      perinatal period. Using a novel serum-free organ culture system, cranial base
      structures were cultured as explants in the presence of BMP4 or noggin, and
      analyzed for morphological and molecular changes. Growth of perinatal cranial
      base explants was inhibited by treatment with noggin, a BMP inhibitor. Exogenous
      BMP4 promoted cartilage growth, matrix deposition and chondrocyte proliferation
      in a dose dependent manner. Correspondingly, expression level of the cartilage
      markers Sox9 and collagen type II were also increased. Alkaline phosphatase and
      collagen type X expression were up-regulated and expressed in ectopic
      hypertrophic chondrocytes after treatment of the cultures with 100 ng/ml BMP4 for
      seven days. This increase in chondrocyte hypertrophy was accompanied by increased
      indian hedgehog (Ihh) and parathyroid hormone/parathyroid hormone related peptide
      (PTH/PTHrP) receptor (PPR) expression, but not increased PTHrP expression. We
      conclude that endogenous BMPs are required to maintain cartilage growth, and
      exogenous BMP4 can enhance cartilage maturation and induce ectopic chondrocyte
      hypertrophy in the cranial base. Therefore, appropriate levels of BMP signaling
      are important for normal cranial base development.

PMID- 14598793
TI  - Comparison of natural resistance in seven genetic groups of meat-type chicken.
AB  - 1. Several studies have shown that genetic variation exists in response to
      various Salmonella strains in mammals and poultry. In the current study
      immunocompetence traits related to natural resistance to Salmonella were measured
      in 7 genetic groups of meat-type chickens (in total 296 chickens involved). 2.
      Variables were measured of both innate (phagocytic activity) and adaptive immune
      responses that are important after a natural or experimental Salmonella
      enteritidis infection. Two traditional Old Dutch Breeds (groups 1 and 2), four
      commercial broiler groups (groups 3 to 6), and one experimental broiler group
      (group 7) were used. In two periods, birds of each group were killed for
      examination at ages between 14 and 35 d post hatch. 3. Significant differences
      between groups were found for most immune variables measured, with significant
      correlations between several of them. All groups produced an adequate immune
      response, of either the innate or the adaptive type. 4. In the current study,
      group 2 showed the highest overall natural resistance, though none of the groups
      was uniformly superior with respect to all traits measured. 5. In conclusion, for
      reliable measurements of general immunocompetence or resistance to Salmonella,
      for example, it is important to measure several aspects of the immune system.

PMID- 14598794
TI  - Pathogenesis of primary biliary cirrhosis.
AB  - Primary biliary cirrhosis is an enigmatic autoimmune disease that predominantly
      affects women. The serologic signatures of PBC are high titer antimitochondrial
      antibodies that are directed at the inner lipoyl domains of the 2-oxo
      dehydrogenase enzymes, particularly PDC-E2. Of note, is that the antibody
      response and the CD4 and CD8 response, are all directed at a similar epitope, the
      inner lipoyl domain. This unique immunologic response suggests that modification
      of the inner lipoyl domain is associated with the immunogenetic basis of disease.

PMID- 14598795
TI  - [Respiratory function monitoring: curves of pressure, volume and flow].
AB  - Respiratory function curves are a graphic representation of changes in volume,
      pressure or flow during the respiratory cycle. These changes can represent
      changes with respect to time (curves of volume-time, pressure-time and flow-time)
      or changes in one variable with respect to another (curves of flow-volume and of
      volume-pressure). Respiratory function curves enable analysis of the
      physiopathology in a patient, detection of changes in clinical status,
      optimization of ventilatory strategy, and evaluation of treatment response. They
      can also be used to facilitate patient comfort, prevent complications and
      iatrogeny, evaluate the course of weaning from mechanical ventilation, and help
      to establish a prognosis. In clinical practice these curves can show the presence
      of air leaks, indicate possible high resistance in the airway, suggest the
      possibility of trapped air, detect the presence of anomalous expiratory volume,
      identify the presence of secretions in the airway or water in the circuit,
      indicate the optimal PEEP, and reveal changes in pulmonary compliance.

PMID- 14598800
TI  - [Early and prodromic symptoms of schizophrenia].

PMID- 14598801
TI  - Best evidence in anesthetic practice: prevention: fondaparinux is better than
      enoxaparin for prevention of major venous thromboembolism after orthopedic
      surgery.

PMID- 14598802
TI  - [Respiratory function monitoring in a child on mechanical respiratory
      ventilation. 2: compliance, resistance, dynamic hyperinflation, pulmonary dead
      space, work of breathing].
AB  - Several parameters can be used to study respiratory mechanics in children on
      mechanical ventilation. Compliance is a measure of the distensibility of the
      respiratory system. In mechanical ventilation two measures of compliance can be
      used. Static compliance (pulmonary distensibility) can be measured in volume
      modes by the application of an inspiratory pause with the respiratory system at
      rest (sedated patients without inspiratory effort). Dynamic compliance does not
      require an inspiratory pause and the respiratory system need not be at rest.
      Compliance can be calculated numerically or expressed graphically in the volume
      pressure curve. Many respirators can calculate inspiratory and expiratory airway
      resistance (including endotracheal tube resistance). Several measures can be used
      to detect dynamic hyperinflation (intrinsic PEEP, auto-PEEP, trapped air volume)
      after application of an expiratory pause. The latest respirators can perform
      these measurements almost automatically. Work of breathing and respiratory effort
      can also be analyzed by measuring several parameters (pressure-time product,
      imposed work of breathing, P 0.1, maximum inspiratory pressure). However, these
      measures have not yet been standardized in children.

PMID- 14598803
TI  - The hunchback of the opera.

PMID- 14598804
TI  - [Conference highlights].

PMID- 14598805
TI  - Two-tailed Fisher's exact test (Cochran-Mantel-Haenzel).

PMID- 14598806
TI  - From surgical imaging...standard and fluoroscopic radiographs demonstrate the
      instability of thoracic compression fractures and the confluence of findings in
      fractures resulting from osteoporosis and those resulting from Kummell's disease.

PMID- 14598808
TI  - Current awareness on yeast.

PMID- 14598807
TI  - From the dermatology clinic...postherpetic neuralgia, in which the source of
      radiculopathy is revealed by examination of the skin.

PMID- 14598809
TI  - Bibliography. Current world literature. Neuro-ophthalmology.

PMID- 14598810
TI  - Bibliography. Current world literature. Ocular manifestations of systemic
      disease.

PMID- 14598811
TI  - From the neurointerventional lab...intraoperative cervical vertebral artery
      injury treated by tamponade and endovascular coiling.

PMID- 14598812
TI  - From the electrodiagnosis lab...H-reflexes in hand muscles after cervical spinal
      cord disease.

PMID- 14598814
TI  - Weighed in the balance? The corporation of apothecaries in Bordeaux, 1690-1790.
AB  - Based on a collective biography of apothecaries, surgeons, and physicians in
      Bordeaux between 1690 and 1790, this article offers a counterbalance to the
      prevailing view of apothecaries. It suggests that, although numbers may have been
      falling and corporations failing elsewhere in France, the favourable situation of
      Bordeaux aided the survival of the corporation of apothecaries in that city. It
      suggests that apothecaries were important in providing a wide range of goods and
      services to patients, and traces their involvement in retail, wholesale, and
      international trade. Control of numbers is shown to be linked to a desire to
      exploit their monopoly of the market, which led to increases in wealth for
      individual practitioners. A change in traditional inheritance strategies is
      linked to a new emphasis on merit, and to knowledge obtained through training
      outside the confines of the apprenticeship system. The 'secrets of the craft' are
      seen to be undermined by the public nature of the emerging science of chemistry.
      The corporation of apothecaries in Bordeaux was transformed through its
      absorption of three new types of practitioner-entrepreneurs, pharmacists, and
      scientists-yet it survived due to the substantial and continuing presence of
      traditional, locally born, and locally trained apothecaries.

PMID- 14598813
TI  - Midwifery and society in restoration York.
AB  - This article is a micro-historical study of the social networks of an elite mid
      wife in seventeenth-century England, and discusses the implications of these
      networks for our understanding of early modem midwifery. Bridget Hodgson was the
      daughter-in-law to the former Lord Mayor of York, and closely connected to some
      of the city's most influential families. Analysis of the connections found in her
      will and the depositions from a defamation trial in which she was involved
      illustrates Hodgson's place among York's elite, but also indicates that her work
      as a midwife took her outside of these circles. This article also compares
      Hodgson's experience with that of her maidservant and deputy, discussing the
      different meanings that midwifery could have for its practitioners, depending on
      their social background. Testimony from the defamation case indicates the ways in
      which her work as a midwife shaped her relationship to parish authorities and to
      the female community. Midwives were expected to report illegitimate births to
      parish officials, an obligation which overlapped with female efforts to control
      the sexuality of neighbourhood women through gossip. This article highlights the
      complexity of the midwife's place in early modern society, and contributes to our
      understanding of this important class of women.

PMID- 14598815
TI  - Mothers' health and babies' weights: the biology of poverty at the Melbourne
      Lying-in Hospital, 1857-83.
AB  - Birth weight remains a major focus of medical research into the relationship
      between pre-natal growth and life course health, and historians have used mean
      birth weight to assess women's standard of living. However, there are intrinsic
      difficulties in inferring maternal health and nutritional status from birth
      weight, and some of the known data sets produce puzzling results. One rich data
      set comes from the Melbourne Lying-in Hospital, 1857-83, and the article
      discusses the complex institutional, social, and economic causes that may
      underlie its apparently counter-intuitive anthropometric results. This data set
      reveals the biological effects differential social conditions can inflict, even
      within an otherwise affluent society.

PMID- 14598817
TI  - "Where doctors differ": the debate on circumcision as a protection against
      syphilis, 1855-1914.
AB  - During the late nineteenth and early twentieth centuries there were two views on
      the relationship between syphilis and male circumcision: one was that
      circumcision provided protection against syphilis, another that circumcision was
      itself a significant source of syphilitic infection. This article reviews this
      debate, relates the first view to an influential article by Jonathan Hutchinson
      in 1855 and considers the subsequent use made of his statistics. It is suggested
      that the original statistics were of dubious value and that the promise of
      protection against syphilis was an additional argument for doctors who were keen
      to introduce universal circumcision of male infants for other reasons, the most
      significant of which was related to the conviction that it would discourage
      masturbation. The article further considers the controversy over whether Jews
      were healthier than other peoples, and the interaction among medical, moral, and
      customary/religious reasons for circumcising boys, and concludes that, while the
      operation never played any role in the control of syphilis, circumcision was
      indeed a significant cause of illness and death among male infants before the
      standardization of aseptic operating techniques.

PMID- 14598816
TI  - Unusual appendicitis.

PMID- 14598818
TI  - Mondays without dread: the Trade Union response to byssinosis in the Lancashire
      cotton industry in the twentieth century.
AB  - Trade unions have often been criticized for their failure to address occupational
      health issues. This article explores their response to byssinosis-a chronic
      respiratory disease caused by exposure to cotton dust that was rife in the
      Lancashire cotton industry in the early nineteenth and twentieth centuries. Using
      the archives of the cardroom and spinning unions, it is demonstrated that trade
      union efforts to combat byssinosis began before the First World War and were
      sustained for over 70 years. During that period, byssinosis became a recognized
      medical condition and a compensatable disease, due in no small measure to the
      trade unions campaigning tirelessly for better dust control, compensation for all
      affected workers, and more medical research.

PMID- 14598819
TI  - Scientific triumphalism and learning from facts: bacteriology and the "Spanish
      flu" challenge of 1918.
AB  - The devastating influenza pandemic known as 'Spanish flu', which killed at least
      20 million people all over the world in 1918, was responsible for the first
      bitter blow inflicted on triumphant bacteriology, fortified by the series of
      resounding successes achieved in identifying the pathogenic agents of terrible
      diseases such as anthrax, cholera, tuberculosis, plague, and syphilis. Over
      confidence and the idea, born of the Pasteur revolution, that every infectious
      disease was caused by a bacterium, had led the scientific community to accept the
      theory put forward by the German bacteriologist, Richard Pfeiffer, who, in 1892,
      believed he had identified the pathogenic influenza agent in a bacterium,
      Haemophilus influenzae. But, while the most appalling epidemic ever to sweep
      through the world since the 'Black Death' of the 1300s was still raging, the
      scientific community had to admit that influenza originated not from a microbe,
      but from a virus. This article aims to reconstruct the enlightening and little
      known cultured/scientific events and issues of the dramatic crisis that
      bacteriology experienced in the autumn of 1918, with the consequent simultaneous
      collapse of both the 'Pfeiffer doctrine' on the microbial origin of influenza and
      the illusion of a world free of infectious diseases. This was an illusion
      destined to surface again at the end of the century and collapse with the advent
      of AIDS.

PMID- 14598820
TI  - Biomedical research and public health in Brazil: the case of Chagas' disease
      (1909-50).
AB  - This article analyses two periods in the history of scientific and social
      legitimization of American trypanosomiasis or Chagas' disease, discovered in
      Brazil in 1909 by Carlos Chagas, physician and researcher at the Instituto
      Oswaldo Cruz. Initially we focus on research during Chagas' lifetime, a phase
      during which the basic statements of the disease were formulated; then, the
      action in the 1940s and 1950s by the researchers of the Centro de Estudos e
      Profilaxia de Molestia de Chagas, located in Bambui, Minas Gerais, is examined.
      The validation of knowledge that made the disease a scientifically and socially
      recognized object occurred through a long process that went beyond not only the
      event of identification of the new disease but the period in which Chagas and his
      collaborators broadened their research. Our hypothesis is that the work done at
      Bambui was responsible for reaching a basic agreement on the pathological
      specificity and social importance of the disease, and was the basis for its
      recognition as an important medical problem for Brazilian public health and for
      its becoming the object of government disease control policy.

PMID- 14598821
TI  - [Tahya Efendi fountain-the resurrection].
AB  - Eighteenth century, Ottoman fountain "Yahya Efendi Cesmesi 1735" was ruined and
      its stones removed in 1982. Due to administrative and burocratic impediments in
      Turkish official courses; it took sixteen years to rebuilt and/or reconstruct the
      fountain in Cerrahpasa Medical School court-yard in 1998. Reconstruction was held
      by Cerrahpasa Department of Obstetrics and Gynecology and supported by University
      of Istanbul. The aim of this article is to show the difficulties faced during its
      reconstruction.

PMID- 14598822
TI  - [The physician of II Bayezid's period: Giyas ibn Muhammed].
AB  - In the middle of the XV. century, the Ottoman Empire was an powerful government
      all the Turc and Islam geography. Many wises and students who belong to the
      Turc's world came here. Isfahanli Giyas b. Muhammed is one of these scientists.
      He finished education in his country and then he came. Amasya and he took lessons
      from Sabuncuoglu about medical information and he returned back to his country.
      He wrote a medical book which named Mir'atu's-Sihha and he dedicated to Ottoman's
      sultan II. Bayezid. In this book's within, there was a poem who exalted the II.
      Bayezid.

PMID- 14598823
TI  - From advanced imaging...where the source of severe acute headache is found in the
      sacrum.

PMID- 14598824
TI  - [Professional life and works of Prof. Dr. Gunsel Kaptagel-Ilal].

PMID- 14598825
TI  - [New publications].
AB  - An account of new publications concerning the history of medicine and history of
      science published in Turkey between 1995-1999.

PMID- 14598827
TI  - [Melatonin: warnings on uncontrolled use].

PMID- 14598826
TI  - [The process of humanization].
AB  - As Stefan Zweig expressed the situation of mankind succinctly: There are key
      moments in history (Sternstunden der Menschheit). Because of their paramount
      importance their events are minimal. Moreover, among them there are those which
      are greater in calibre than the ones quoted in Stefan Zweig's Sternstunden der
      Menschheit. These are the turning points of history. At first glance we can
      enumerate four major events: first and foremost, the enormous shift of certain
      communities from food-gathering to agriculture around 8000 BC mainly in Southwest
      Asia (Mesopotamia). Second, the introduction of the writing system at circa 3500
      BC by the Sumerians again in Southwest Asia. Last but not least that tremendous
      innovation, maybe the greatest in history, once more in western Asia, the
      emergence of monotheistic religions based on revelation, and the origination of
      philosophy-science within the realm of the Antique Aegean civilization. Man's
      basic reality is biotic. He shares this very particularity with all other living
      beings of this world. Livingness, so far as we know, is a peculiarity of our
      planet, the Earth. The unfolding of livingness and ultimately the emergence of
      man as a living being is apparently covered by evolution. Hominization is the
      biotic, whereas humanization represents the cultural (or spiritual) aspect of
      becoming the human being. Hominization and humanization complement one another to
      bring about the human wholeness. Hominization, or put it in another way, the
      evolutionary aspect is, indeed, not the beginning of the story. There still
      remains a lower layer, in the ontological sense of the team, to be tackled; and
      that is the physical one. Just as with every living thing, man's most fundamental
      building blocks are of a physico-chemical-i.e. subatomic, atomic and molecular
      nature.

PMID- 14598828
TI  - STROKE: From Bench to Bedside, ASPET-Ray Fuller symposium, San Diego Marriott
      Hotel, San Diego, CA, USA, April 10-11, 2003.

PMID- 14598829
TI  - CNS drugs at the Experimental Biology, 2003 Meeting, San Diego, CA, April 11-15,
      2003.

PMID- 14598830
TI  - Psychiatric Drug Discovery and Development, Princeton, NJ, USA, June 23-24, 2003.

PMID- 14598831
TI  - [Must the data on the deceased be preserved?].

PMID- 14598832
TI  - Optimising HIV Treatment--Building on Experience. Proceedings of a symposium. 15
      March 2002, Seville, Spain.

PMID- 14598833
TI  - [The Hekimbasi and Hekimbasilik in the Ottoman Empire].
AB  - The hekimbasilik is an important society in the Empire of Ottoman. The Hekimbasi
      protected the health of the monarch and his family and applied health system,
      borders of the empire during 350 years. In the past, 42 Hekimbasi worked in this
      society. They received education and their medical information in classic ottoman
      Medrese. In addition to this, they worked as Muslim judge and Medrese hodja.

PMID- 14598834
TI  - [The calligrapher and the doctor].
AB  - Famous Turkish calligrapher Musa Azmi Hamid Aytac (Am'idi) partially known life
      story and his family has been summarised by his relatives. The only three tougra
      like unpublished original calligrafics which has designed by Hamid to his
      relatives "l) Dr. Fethi Aksu, 2) Feridun Aksu, 3) Fikret Aksu" has been presented
      in this brief biography.

PMID- 14598835
TI  - [Dr. Besim Omer Akalin and population policy in Turkey].
AB  - Dr. B. Omer Akalin who was the founder of modern obstetric and who made efforts
      on social fields also produced works related with problem of population.
      Successive wars, infections diseases and child mortality that cause our
      population decrease. Dr. B. Omer Akalin dealt with necessary precautions for
      combating against causes that decreases population and for a healty society.

PMID- 14598836
TI  - Proceedings of the 13th Novo Nordisk Symposium on Growth Hormone and
      Endocrinology and of the SGA/IUGR Satellite Symposium. Budapest, Hungary, April
      11-13, 2002.

PMID- 14598837
TI  - Bariatric surgery.

PMID- 14598838
TI  - [Evaluation of the last 50 years of the progress in immunology in our country].
AB  - Different methods of vaccination have been observed in the ancient civilizations,
      to protect themselves from diseases. Pontus King, Mitridates Eupaton (132-63
      B.C.), established the basic principles of Immunology unconsciously. Since he was
      scared of being poisoned all the time, he looked for an antidote. He gave the
      poison in little amounts to the prisoners and found a way to be immune against
      poisons with immunization. He turned out to be the first immunologist. The
      essential idea of immunology was established by the idea of immunity developed by
      Jenner and Pasteur, against cholera and smallpox. In our country, immunology has
      evolved from bacteriology and virology, as well. Actually, in the ancient times,
      Turks used variolation in their daily lives (from human to human). In the last 50
      years, immunology progressed both in our country and in the world rapidly and
      played an important role in the etiopathogenesis of the diseases of different
      systems. Also, through a philosophical point of view, it brought the necessity of
      a holystic evaluation for the description of human health.

PMID- 14598839
TI  - [Some documents on the education in the Ottoman Medical School].
AB  - After the foundation of the Ottoman Medical School in 1838 in Galatasaray in
      Istanbul, we have examined in the Ottoman archives some documents about the
      physician and professors who are in charge of the Ottoman Medical School. We have
      learned with these documents that the chief physician Abdulhak Molla was honored
      with a mension and an ordonnance was given by the sultan for the publication of
      his book, and in the chemical laboratory of the medical school all of the
      examinations are done without payment. In 1867 when it was an epidemic of cholera
      in Istanbul, Mr. Georges Ralli was charged in the Hospital of Humbarahane. The
      directory of the Medical School ordered cupboards for the School. When the
      typhoid fever epidemic appeared in 1865 in Istanbul a physician was attended in
      the Medical School. An order was given by the sultan for the pick up of the
      medical opium in the mounth Uludag for the pharmacy of the medical school and for
      the exercise of the lessons of obstetrics in the Medical School, a lady was
      invited from Austria. Many professors in the Medical School received different
      compensations.

PMID- 14598840
TI  - Reproductive endocrinology and infertility.

PMID- 14598841
TI  - Current awareness in prenatal diagnosis.

PMID- 14598842
TI  - Molecular genetic analysis of chromosome 9 candidate tumor-suppressor loci in
      bladder cancer cell lines.

PMID- 14598843
TI  - Prognostic value of proliferative activity and nuclear morphometry for
      progression in TaT1 urothelial cell carcinomas of the urinary bladder.

PMID- 14598844
TI  - Expression of cathepsin D in urothelial carcinoma of the urinary bladder: an
      immunohistochemical study including correlations with extracellular matrix
      components, CD44, p53, Rb, c-erbB-2 and the proliferation indices.

PMID- 14598845
TI  - High frequency ultrasound (HFU) helps differentiating cervical lymph nodes from
      parathyroid adenomas.

PMID- 14598846
TI  - Electric belt.

PMID- 14598847
TI  - Womens heart health series: a mini-symposium - in reply.

PMID- 14598848
TI  - Comments on: case presentation of gastrinoma combined with gastric carcinoid with
      the longest survival record -Zollinger - Ellison syndrome: pathophysiology,
      diagnosis and therapy.

PMID- 14598849
TI  - Developing rural information and assistance programs.
AB  - Older people living in rural areas face unique challenges, not only in accessing
      benefits and services, but also in gathering information about programs that can
      help them. In this brief, we tackle the issue of information and assistance (I&A)
      in rural areas by profiling an area agency on aging that has successfully
      established an I&A program designed to meet the needs of rural elders. We offer
      tips from the agency's experience and insight from experts in the field.

PMID- 14598850
TI  - Advancing an ethical framework for long-term care.
AB  - This article represents an effort to formulate an ethical framework for long-term
      care with the explicit purpose of providing a catalyst to promote further
      discourse and expand consideration of what an ethic of long-term care might
      entail. Grounding the discussion, an introduction to traditional ethical
      philosophy is presented, focusing mainly on the fundamentals of deontological and
      teleological ethical theories. Attention then shifts to a review of the more
      frequently cited principles found in the long-term care ethics literature,
      followed by a critique of the current reliance upon principlism to resolve
      ethical dilemmas in long-term care. In response to this criticism, an agent
      driven ethical framework stressing dignity and respect for personhood, drawn from
      the philosophy of Immanuel Kant, is advanced.

PMID- 14598851
TI  - Eggs, embryos, and professional ethics.

PMID- 14598852
TI  - Human cloning: assessing the ethical and legal questions.

PMID- 14598853
TI  - Whose genes are they anyway?

PMID- 14598854
TI  - Vascular factors and risk of dementia: design of the Three-City Study and
      baseline characteristics of the study population.

PMID- 14598855
TI  - The ethics of conducting social-science research on the Internet.

PMID- 14598856
TI  - Scholarly watchdogs for an ethical netherworld: researchers form group to track
      and study sale of body parts for organ transplants.

PMID- 14598857
TI  - Purification and characterization of apyrase from the tick, Ornithodoros
      savignyi.

PMID- 14598858
TI  - Linking research and innovative clinical practice: the story of diabetes
      mellitus.
AB  - Research into diabetes mellitus and the clinical practice of diabetology are a
      fascinating illustration how the accumulation of knowledge leads to changing
      scientific theories and paradigms. The pivotal point in the history of diabetes,
      the discovery of insulin and its introduction to treatment, was one of the most
      spectacular events in medicine. Later, diabetes care provided, among other
      developments, models for multidisciplinary approach to treatment and the
      blueprint for community-based epidemiological studies. The history of diabetology
      also illustrates the role of chemistry, and later laboratory medicine, in the
      management of disease. This article is an introduction to the special issue of
      Clinical Chemistry and Laboratory Medicine, focused on diabetes mellitus and its
      complications.

PMID- 14598859
TI  - Insulin resistant states and insulin signaling.
AB  - The incidence of type 2 diabetes mellitus (T2D) and obesity is increasing rapidly
      worldwide, reaching epidemic proportions. Insulin resistance is a key feature in
      both conditions and plays an important pathophysiological role. Over the last two
      decades a central role in the origin of insulin resistance has emerged for
      defects in the intracellular insulin signaling cascade leading to glucose uptake.
      Herein, we will 1) review insulin signaling pathways leading to glucose uptake,
      2) review mouse models of insulin resistance that demonstrate the
      pathophysiologic importance of specific defects of these pathways and 3) discuss
      the molecular basis for insulin resistance in some human disease states known to
      be associated with insulin resistance. Finally, we will briefly mention some
      novel treatment targets for T2D stemming from this knowledge.

PMID- 14598860
TI  - Diabesity: an inflammatory metabolic condition.
AB  - Diabesity, that is to say, obesity-dependent diabetes, has emerged as a major
      public health problem. Though diabesity is basically explained by insulin
      resistance and pancreatic beta cell dysfunction, new paradigms have evolved to
      explain these alterations in the context of the modern epidemics of obesity and
      diabetes. Among these, the association of inflammation with obesity is an
      important component of the common soil from which diabetes and cardiovascular
      diseases (CVD) derive. This Review presents our epidemiological findings, based
      primarily on the ARIC Study, in the context of the other epidemiological studies
      supporting the inflammatory nature of diabetes, CVD and the metabolic syndrome.
      We also review the characteristics of the innate immune system, including the
      molecular interface of innate immunity with metabolism, components of which are
      responsible for the presence of a state of mild, chronic and systemic
      inflammation related to diabesity. Finally, we present obesity as an inflammatory
      condition, obesitis, and propose a conceptual framework that integrates the
      epidemiological findings with new provocative basic science results.

PMID- 14598861
TI  - Plasma adiponectin and hyperglycaemia in diabetic patients.
AB  - The insulin-sensitising adipose hormone adiponectin is reduced in type 2 diabetic
      patients. We assessed the relationships between plasma adiponectin and chronic
      hyperglycaemia. Adiponectin levels and glycated haemoglobin (HbA1c) were measured
      at enrolment and after 90 days in 16 patients with type 2 diabetes aged (mean +/-
      SEM) 63.0 +/- 0.6 years, with body mass index (BMI) 30.2 +/- 0.5 kg/m2 and HbA1c
      concentration 7.4 +/- 0.1%, who did not modify their hypoglycaemic treatment
      during the observation period. Furthermore, plasma adiponectin was measured in 29
      adult patients with type 1 diabetes and compared with 29 control subjects matched
      for sex, age, BMI, waist circumference and bioimpedance-estimated fat mass. In
      type 2 diabetic patients at enrolment, adiponectin concentration correlated with
      BMI (r = -0.46; p < 0.05), but not with HbA1c. During the prospective
      observation, variations of adiponectin showed a significant correlation with
      variations of BMI (r = -0.47; p < 0.01), but not with variations of HbA1c
      concentration. These results were confirmed by multivariate analysis after
      adjustment for sex and age. Adiponectin levels in type 1 diabetic patients (380.8
      +/- 13.7 ng/ml in women, 192.5 +/- 13.9 ng/ml in men) were significantly (p <
      0.05) higher than in control subjects (277.6 +/- 11.0 ng/ml in women, 102.7 +/-
      5.1 ng/ml in men); plasma adiponectin correlated significantly with BMI and waist
      circumference, but not with HbA1c. In conclusion, the reduction of plasma
      adiponectin levels in type 2 diabetic patients does not appear to be determined
      by chronic hyperglycaemia. Adiponectin levels are increased in type 1 diabetes,
      but this phenomenon is not attributable to differences in nutritional status or
      body composition.

PMID- 14598862
TI  - Platelet function and acetyl-coenzyme A metabolism in type 1 diabetes mellitus.
AB  - Blood platelets take up glucose through insulin-independent GLUT-3 transporter.
      It is, however, unclear how diabetes affects further steps of glucose and glucose
      derived acetyl-coenzyme A (CoA) metabolism in platelets. There is no evidence to
      explain whether these changes are linked to the disease-induced disturbances in
      platelet function. We found that activities of some key enzymes of glucose and
      acetyl-CoA metabolism in platelets were elevated in diabetes. Activities of
      hexokinase, pyruvate dehydrogenase and ATP-citrate lyase in diabetic platelets
      were found to be increased by 53, 56 and 88%, respectively. Accordingly, diabetes
      brought about 86% increase of platelet acetyl-CoA and activation of malonyl
      dialdehyde synthesis as well as spontaneous and thrombin-induced platelet
      aggregation by about 56, 50 and 15%, respectively. Significant correlations have
      been observed between some parameters of acetyl-CoA metabolism, platelet function
      and serum fructosamine in diabetic patients but not in healthy individuals. Our
      findings indicate that increased platelet activity in diabetic subjects may, at
      least in part, result from chronic hyperglycaemia-induced changes in acetyl-CoA
      metabolism, yielding an increase in its concentration in platelets.

PMID- 14598863
TI  - Oxidative stress in diabetes.
AB  - Increasing evidence in both experimental and clinical studies suggests that there
      is a close link between hyperglycemia, oxidative stress and diabetic
      complications. High blood glucose level determines overproduction of reactive
      oxygen species (ROS) by the mitochondria electron transport chain. High
      reactivity of ROS determines chemical changes in virtually all cellular
      components, leading to DNA and protein modification and lipid peroxidation.
      Measurement of biomarkers such 8-hydroxy-2'deoxyguanosine (8-OHdG), isoprostanes,
      malondialdehyde (MDA) and nitrotyrosine is a useful tool to assess the oxidative
      stress of the organism. Knowledge of the mechanisms of ROS damage of is the first
      step for development of new therapeutic molecules and for rationalizing the use
      of existing drugs.

PMID- 14598864
TI  - Carbonyl stress and diabetic complications.
AB  - Advanced glycation irreversibly and progressively modifies proteins over time and
      yields the advanced glycation end-products (AGE). AGEs are thought to contribute
      to the development of atherosclerosis and of diabetic and uremic complications.
      Their inhibition has thus become a therapeutic goal. In this article, we discuss
      the role of various reactive carbonyl compound (RCOs) in the genesis of AGEs,
      postulate the existence of "carbonyl stress" in complicated diabetes and,
      finally, discuss therapeutic perspectives.

PMID- 14598865
TI  - Chemical modification of proteins by lipids in diabetes.
AB  - Advanced glycation and lipoxidation end-products (AGE/ALE) increase in tissue
      proteins with age and at an accelerated rate in diabetes. This Review focuses on
      the nature and source of AGEs/ALEs and the factors affecting their formation in
      tissue and plasma proteins. Lipids are identified as an important source of
      chemical modification of proteins in diabetes, and the role of diabetes,
      dyslipidemia and renal disease in formation of AGEs/ALEs is reviewed. The article
      concludes with a discussion of ELISA assays for AGEs/ALEs and the merits of
      measuring AGEs/ALEs in the clinical laboratory.

PMID- 14598866
TI  - Glyoxal and methylglyoxal levels in diabetic patients: quantitative determination
      by a new GC/MS method.
AB  - Determination of glyoxal and methylglyoxal levels in plasma is of great interest,
      since it allows us to evaluate oxidation processes occurring in glycated
      proteins. A method based on a simple derivatization procedure followed by gas
      chromatography/mass spectrometry (GC/MS) analysis has been developed. Ten
      diabetic patients were evaluated before and after improvement of glycemic
      control. Fasting plasma glucose, hemoglobin A1c (HbA1c), advanced glycation end
      products (AGE), pentosidine, glyoxal and methylglyoxal levels were measured. The
      percentage decreases of the levels of fasting plasma glucose, HbA1c and AGE were
      larger than those of pentosidine, glyoxal and methylglyoxal. These results may be
      explained by considering the different position of these compounds in the
      Maillard reaction pathways: these two sets of metabolic parameters give different
      pictures of patients' metabolic control. The measurement of glyoxal and
      methylglyoxal may be particularly important in the evaluation of the possible
      effect of oxidative stress. Other metabolic pathways can contribute to glyoxal
      production, and the observed minor decrease in these compounds can be, in
      principle, ascribed to such effect. However, a similar behavior of pentosidine
      indicates that these alternative pathways can be only partially responsible for
      glyoxal and methylglyoxal production.

PMID- 14598867
TI  - Dyslipidemia in patients with type 2 diabetes. relationships between lipids,
      kidney disease and cardiovascular disease.
AB  - Type 2 diabetes mellitus is a leading cause of morbidity and mortality.
      Cardiovascular disease (CVD) is the most prevalent complication and primarily
      accounts for the excess morbidity and mortality in diabetic patients, but
      microvascular complications, such as kidney disease and retinopathy, are frequent
      and contribute to the total disease burden. Lipid abnormalities in patients with
      type 2 diabetes are a major problem and associated with the increased risk of
      CVD. The most common pattern of dyslipidemia in these patients consists of
      elevated levels of triglycerides and low levels of high-density lipoprotein
      cholesterol. Low-density lipoprotein levels in these patients are often similar
      to that of the nondiabetic population, although there may be important
      qualitative differences in the pattern that contribute to the increased risk of
      CVD. Abnormal levels of urinary albumin occur in 30-40% of patients with type 2
      diabetes and the presence of kidney disease enhances the mortality from CVD.
      Microalbuminuria, an early marker of diabetic nephropathy, is an independent risk
      factor for CVD. The increased levels of urinary albumin secretion may represent a
      more generalized vascular damage than renal microvascular injury alone. This
      Review focuses on the significance of diabetic dyslipidemia and microalbuminuria
      to CVD risk as well as to kidney complications. We also discuss the role of
      aggressive therapy to ameliorate vascular injury in the diabetic patient and
      reduce or prevent the cardiovascular and renal consequences of the disease.

PMID- 14598868
TI  - Haemoglobin A1c--a marker for complications of type 2 diabetes: the experience
      from the UK Prospective Diabetes Study (UKPDS).
AB  - Haemoglobin A1c (HbA1c) is the pre-eminent factor for quantifying the risk of
      complications in patients with diabetes and for monitoring glycaemia.
      Intervention to lower blood glucose in the two landmark clinical trials, the UK
      Prospective Diabetes Study (UKPDS) and the Diabetes Control and Complications
      Trial (DCCT), led to a reduction in the microvascular complications of diabetes.
      Glycaemic status could be compared in the UKPDS and DCCT as the Bio-Rad Diamat
      HPLC analyser, as used in the DCCT, was introduced in 1989 for measurement of
      HbA1c in the UKPDS, after liaison with the DCCT. Results from other methods used
      for measurement of glycated haemoglobin during the UKPDS were aligned to this
      method. The Bio-Rad Diamat analyser in the central laboratory for the UKPDS,
      reference range 4.5-6.2% HbA1c, was certified as comparable to the DCCT by the
      National Glycohemoglobin Standardization Program in 1998. A median difference in
      HbA1c of 0.9% was maintained over 10 years between the intensively and
      conventionally treated groups in the UKPDS (7.0% vs. 7.9% HbA1c) despite HbA1c
      increasing over time. Clinical care was transferred to general practitioners
      after the end of the main glucose control study for post-study monitoring. Over
      the first 3 years of post-study monitoring, HbA1c rose slightly in the previously
      intensively treated group with no appreciable increase in the conventional group,
      due to intensification of therapy. At near-normal HbA1c, < 6%, the updated mean
      value chosen to reflect glycaemic exposure throughout the UKPDS, the incidence of
      myocardial infarction was 2-3 times that of microvascular disease, with similar
      incidences for both complications at >10% updated mean HbA1c. Relationships
      between the risk of complications of type 2 diabetes and updated mean HbA1c had
      no observable thresholds. The UKPDS risk engine derived from the UKPDS database
      calculates coronary heart disease risk using HbA1c as a continuous variable and
      could now replace the Framingham equations for patients with type 2 diabetes.

PMID- 14598870
TI  - Haemoglobin A1c: analysis and standardisation.
AB  - The measurement of glycated haemoglobin has become centrally important in the
      monitoring of glycaemic control in the patient with diabetes. A number of
      analytical techniques have been described to measure this important haemoglobin
      fraction, and the fraction measured depends on the technique used; this has
      resulted in laboratories reporting different fractions i.e., HbA1, HbA1c and
      total glycated haemoglobin. This paper outlines methods currently used in
      clinical laboratories for the measurement of this glycated fraction. It describes
      the principles behind these methods and goes on to describe the new IFCC
      reference method, which will be used in the future to standardise methods used in
      the clinical laboratory. Analytical goals and factors that interfere with methods
      are also discussed.

PMID- 14598869
TI  - Glycated hemoglobin standardization--National Glycohemoglobin Standardization
      Program (NGSP) perspective.
AB  - The Diabetes Control and Complications Trial (DCCT) and the United Kingdom
      Prospective Diabetes Study (UKPDS) demonstrated conclusively that risks for
      complications in patients with diabetes are directly related to glycemic control,
      as measured by glycated hemoglobin (GHb). Many diabetes organizations worldwide
      now recommend GHb targets in terms of DCCT/ UKPDS hemoglobin A1c (HbA1c).
      However, in 1993 there was a lack of comparability of GHb test results among
      methods and laboratories that represented a major obstacle to meaningful
      implementation of specific guidelines for diabetes care. The National
      Glycohemoglobin Standardization Program (NGSP) was implemented to enable
      laboratories to report DCCT/UKPDS-traceable GHb/HbA1c results. The number of
      methods and laboratories certified by the NGSP as traceable to the DCCT has
      steadily increased. Proficiency testing results show marked improvement in the
      comparability of GHb results. By the end of 2002, 98% of surveyed laboratories (n
      = approx. 2000) reported GHb results as HbA1c or equivalent compared to 50% in
      1993. Ninety-seven percent of laboratories used an NGSP-certified method. For
      most certified methods in 2002, between-laboratory CVs were < 5%. For all
      certified methods in 2002, the mean HbA1c value (%) was within 0.8% HbA1c from
      the NGSP target at all HbA1c concentrations. The vast majority of laboratories in
      the US are now reporting results that are traceable to DCCT/UKPDS outcomes.

PMID- 14598872
TI  - Evaluation of portable blood glucose meters. Problems and recommendations.
AB  - Various guidelines are in use for validating blood glucose meters. There are
      currently no analytical guidelines for validating procedures available for non
      invasive or minimally invasive blood glucose meters. As a result manufacturers of
      these meters need to comply with different regulations in different countries
      with concomitant high costs. Some of the differences between different guidelines
      will be discussed in this article and recommendations for improvement will be
      presented.

PMID- 14598871
TI  - Point-of-care testing in diabetes mellitus.
AB  - Diabetes mellitus is an excellent case study of the evolution, and successful
      application, of point-of-care testing. It offers a valuable history of the way in
      which technology has evolved, and continues to evolve, to meet the needs of
      patients whilst also providing for a more optimal delivery of care. Diabetes
      mellitus is also a good exemplar of where test and treatment regimes must operate
      in complete harmony in order to achieve the greatest benefit. Thus whilst the
      measurement of blood glucose is central to the screening, diagnosis and
      management of diabetes, it is in the latter use, largely related to supporting
      compliance with therapy, that point-of-care testing is of greatest relevance. In
      addition, there are other tests, more associated with the management of diabetes
      and early detection of the complications associated with diabetes, that are
      appropriate to the point-of-care testing modality. This Review will focus on the
      developments in technology and the harnessing of this innovation to support the
      delivery of clinical, organisational and economic benefits in the care of
      patients with diabetes mellitus.

PMID- 14598873
TI  - Measurements of glucose on the skin surface, in stratum corneum and in
      transcutaneous extracts: implications for physiological sampling.
AB  - Obtaining representative physiological samples for glucose analysis remains a
      challenge especially when developing less invasive glucose monitoring systems for
      diabetic patients. In the present study the glucose content of the stratum
      corneum was compared with the amount of glucose obtained by short aqueous
      extractions from a site on the dorsal wrist, using high pressure liquid
      chromatography with pulsed amperometric detection. Ten successive aqueous 1
      minute extractions of the site yielded a total of 60 ng cm(-2). The total glucose
      content of the stratum corneum of the site, determined from 30 successive tape
      strippings of the site, was 360 ng cm(-2). After tape-stripping, the
      transcutaneous aqueous extraction rate was 86 +/- 13 ng cm(-2) min(-1), compared
      with rates of 80-600 ng cm(-2) min(-1) obtained with suction effusion or
      microdialysis after tape-stripping. Glucose on the surface of the skin and within
      the stratum corneum should be considered as sources of extraneous glucose
      contamination during testing of less invasive glucose monitoring devices.

PMID- 14598874
TI  - Biological variability of albumin excretion rate and albumin-to-creatinine ratio
      in hypertensive type 2 diabetic patients.
AB  - The importance of measuring microalbuminuria is well established. However, only
      scanty data are available concerning the biological variability of albumin
      excretion in type 2 diabetic subjects. We report our experience from a large
      clinical trial of a new antihypertensive drug (Lercanidipine) designed to reduce
      albumin excretion and blood pressure in type 2 diabetic patients with
      hypertension and microalbuminuria. Eighty seven patients with persistent
      microalbuminuria were studied within 1 year of the clinical trial. The
      measurements were performed on blood and timed urine samples frozen at -80
      degrees C and shipped to a central laboratory unit. Preliminary experiments were
      performed to assess albumin stability in urine under various conditions (4
      degrees C, -20 degrees C and -80 degrees C), particularly with regard to the
      albumin/creatinine ratio. Urine samples can be stored up to 3 weeks at 4 degrees
      C or up to 2 months at -80 degrees C. The biological variability of the albumin
      excretion rate was 25.7%, while that of the albumin/creatinine ratio was 13.4%.
      These data are useful in defining the analytical goals of imprecision for
      microalbuminuria (CV = 13% for albumin, and CV = 6% for albumin/creatinine
      ratio). No correlation between albumin/creatinine ratio and HbA1c was found in
      the cohort of 61 microalbuminuric patients who completed the trial. The results
      of this study confirm that the albumin/ creatinine ratio is much more suitable
      for monitoring albumin excretion in longitudinal studies than the albumin
      excretion rate.

PMID- 14598875
TI  - Clinical and laboratory evaluation of specific chemiluminescence assays for
      intact and total proinsulin.
AB  - Measurement of proinsulin is an important tool in the assessment of pancreatic
      beta cell function in patients with type 2 diabetes. The goal of this study was
      to perform a technical and clinical evaluation of two specific chemiluminescence
      assays (CLIA) for the determination of intact and total proinsulin in comparison
      to a radioimmunoassay (RIA) method for the measurement of total proinsulin. A
      total of 191 serum samples from patients with type 2 diabetes were used to
      perform a regression analysis. The total proinsulin CLIA showed higher proinsulin
      levels than the two other proinsulin assays (mean +/- SD: 55.9 +/- 58.1 pmol/l, p
      < 0.001 in both cases). The intact proinsulin CLIA (22.5 +/- 20.9 pmol/l) gave
      lower values than the RIA for total proinsulin (31.9 +/- 25.4 pmol/l, p < 0.001
      vs. CLIA, r = 0.948). The RIA has a 95% cross-reactivity to des31,32-proinsulin,
      which is secreted during the process of beta cell deterioration. The intact
      proinsulin CLIA has virtually no cross-reactivity with des31,32-proinsulin (1.4%)
      and is therefore more specific for intact proinsulin than the RIA. This test does
      not measure further degradation products, in contrast to the total proinsulin
      CLIA. The CLIA is, therefore, more specific for total proinsulin measurement than
      the RIA. Both CLIAs could be performed much faster (4 hours) than the RIA method
      (75 hours/ 4 days). In conclusion, the CLIA methods show improved qualitative
      outcomes, higher specificity and several technical advantages over the RIA
      method.

PMID- 14598876
TI  - Clinical impact of the new criteria for the diagnosis of diabetes mellitus.
AB  - In 1997 the American Diabetes Association lowered the threshold for diagnosis of
      diabetes from a fasting plasma glucose concentration of 7.8 mmol/l to 7.0 mmol/l
      and advised that the oral glucose tolerance test no longer be used in routine
      clinical practice. In 1999 the World Health Organization endorsed the reduction
      in fasting plasma glucose threshold but recommended retaining the oral glucose
      tolerance test for anyone with impaired fasting glucose (6.1 mmol/l-6.9 mmol/l).
      This Review discusses the impact of these changes on the prevalence of diabetes
      and examines the implications for individuals and specific high-risk groups. The
      phenotype of those diagnosed with diabetes and the predictive value for the
      development of complications according to the different criteria are compared. It
      is clear that these changes in diagnostic criteria have major importance both for
      individuals and for resource planning at a national level.

PMID- 14598877
TI  - The effect of the new ADA and WHO guidelines on the number of diagnosed cases of
      diabetes mellitus.
AB  - In the new lowered diagnostic discriminator for diabetes mellitus (DM) from the
      American Diabetes Association (ADA), fasting peripheral venous plasma glucose (f
      vPG) of 7.0 mmol/l is identical to the 99.9 centile of f-vPG (7.05 mmol/l, 95%CI:
      6.91-7.20 mmol/l) in a low-risk reference population. We investigated its
      diagnostic concordance with other diagnostic discriminators. As no index test is
      available for DM we used the ADA discriminator as gold standard. We isolated a
      low-risk reference population (n = 424) from a randomised general population (n =
      726) by ruling out of all cases with clinical and biochemical risk indicators for
      DM. We based our analysis on measurements traceable to primary standard
      concentration, a bias of < 1.5% and CV% < 2.5. The distribution of the fasting
      capillary whole blood glucose (f-CBG; mmol/l) in the reference population was in
      Gaussian with the 99.9 centile of 6.62 mmol/l (95% CI 6.47-6.77 mmol/l) and the
      97.5 centile of 5.92 mmol/l (5.82-6.02 mmol/l). The 6.1 mmol/l f-CBG WHO limit
      corresponds approximately to the 97.6 centile, and this limit is thus not
      traceable to the ADA discriminator, which corresponds to f-CBG of 6.4 mmol/l.
      This is the case in groups only, as recalculation will introduce unpredictable
      errors. Thus, in our general population a varying number of subjects will be at
      risk of DM as a mere consequence of different limits. The f-CBG limit of 6.1
      mmol/l will thus lead to 2.4% false-positive diagnoses or, in EU, to around 44 x
      10(6) adults being diagnosed. The number of cases at risk of DM vary from 5.4 x
      10(6) to 44 x 10(6) in EU. We conclude that application of different diagnostic
      limits results in highly variable number of diagnosed DM cases, and therefore one
      diagnostic discriminator is needed to provide reproducible diagnoses.

PMID- 14598878
TI  - Detecting type 2 diabetes by a single post-challenge blood sample.
AB  - In the recent American Diabetes Association (ADA)/WHO recommendations, the oral
      glucose tolerance test (OGTT) was replaced by the measurement of a single fasting
      glucose concentration with a decision limit for the detection of type 2 diabetes
      mellitus (DM) reduced. This proposal, however, misses all cases of isolated post
      prandial hyperglycaemia. Therefore, a study was undertaken to develop a post
      challenge, one-sample mode of diagnosis. OGTT was performed in 240 high-risk
      subjects who were suspected to suffer from type 2 DM. Glucose concentrations were
      determined at 30 min intervals in the capillary blood, venous blood and plasma,
      and insulin was determined in venous plasma only. The test results were
      classified in non-disease and disease group according to the decision limits
      recommended by ADA/WHO. Furthermore, the early insulin response and an insulin
      sensitivity index were used to determine new cut-off values. These were
      identified as the concentrations demonstrating the highest diagnostic efficiency
      and were lower than the WHO limits. The 2 h post-load plasma concentration led to
      higher efficiency at a cut-off value of 9.0 mmol/l glucose (162 mg/dl) compared
      to concentrations of samples taken in the fasting state, at an earlier time of
      the OGTT, or in venous and capillary blood. Under this condition, 72 diabetic
      patients (35%) were detected in the study group (n = 207), whereas only 36 (17%)
      were found with one sample in the fasting state and 53 (26%) with two samples
      using the ADA/WHO criteria. Therefore, a single venous plasma sample taken after
      2 h post-glucose challenge appeared to be most efficient for the early detection
      of DM.

PMID- 14598879
TI  - Laboratory tests in diagnosis and management of diabetes mellitus. Practical
      considerations.
AB  - The clinical laboratory plays an essential role in both the diagnosis and
      therapeutic monitoring of diabetes mellitus. Here, a short review of the main
      laboratory parameters used in the monitoring of diabetes--glucose (including
      point-of-care testing), HbA1c and microalbuminuria--is presented. The impact of
      pre-analytical and analytical performance criteria on the clinical decision
      making process is discussed.

PMID- 14598880
TI  - Obesity, glucose intolerance and diabetes and their links to cardiovascular
      disease. Implications for laboratory medicine.
AB  - This article provides an overview of the role of metabolite toxicity, low-grade
      inflammation and disturbed cellular signaling in obesity, glucose intolerance and
      diabetes. It also highlights links between this continuum of deteriorating
      glucose tolerance and atherosclerosis. Obesity, diabetes mellitus, and
      cardiovascular disease are all related to diet and to the level of physical
      activity. They have reached epidemic proportions worldwide. Glucose intolerance
      and diabetes increase the risk of atherosclerotic events. Moreover, obesity, and
      glucose intolerance or diabetes, are components of the metabolic syndrome, which
      also imparts an increased cardiovascular risk. There is increasing recognition
      that common mechanisms contribute to diabetes and cardiovascular disease.
      Following increased calorie intake and/or decreased physical activity, fuel
      metabolism generates excess of 'toxic' metabolites, particularly glucose and
      fatty acids. Homeostasis is affected by the endocrine output from the adipose
      tissue. Reactive oxygen species are generated, creating oxidative stress, which
      exerts major effects on signaling pathways, further affecting cellular metabolism
      and triggering low-grade inflammatory reaction. This perspective on the diabetic
      syndrome has been reflected in the approach to its treatment, which integrates
      maintenance of glycemic control with primary and secondary cardiovascular
      prevention. Laboratory medicine should support diabetes care with an integrated
      package of tests which, in addition to glycemic control, enable assessment and
      monitoring of the risk of microvascular complications as well as cardiovascular
      disease.

PMID- 14598881
TI  - Role of insulin-like growth factor binding proteins (IGFBPs) in breast cancer
      proliferation and metastasis.
AB  - Cancers of the breast, prostate, and lung commonly metastasize to the bone
      resulting in osteolysis, pathologic fracture, pain and significant clinical
      morbidity. To date, the reason for such selectivity in the site of metastasis
      remains largely unknown. The bone is a rich source of many chemokines and growth
      factors, including: insulin-like growth factor (IGF) I and II, transforming
      growth factor-beta (TGF-beta), interleukins, and tumour necrosis factor-alpha
      (TNF-alpha). We propose that exposure of breast cancer cells to the bone
      microenvironment results in alterations in gene expression that favour the growth
      and proliferation of tumour cells in the bone. To investigate this hypothesis,
      MDA-MB-231 breast carcinoma cells were exposed to bone-derived conditioned media
      (BDCM) generated by culturing fetal rat calvaria for 24 h under serum free
      conditions. Using cDNA microarray technology, we have identified the insulin-like
      growth factor family of binding proteins (IGFBPs) as genes whose expression
      profiles are consistently and significantly altered with exposure to this
      simulated bone environment in vitro, when compared to untreated controls. Our
      data suggests that the upregulation of IGFBP-3 seen with exposure to the bone
      microenvironment is directly linked to an increase in TGF-beta mediated cell
      proliferation. Furthermore, this process appears to be functioning through an IGF
      independent mechanism.

PMID- 14598882
TI  - Immunization with a vaccine that combines the expression of MUC1 and B7 co
      stimulatory molecules prolongs the survival of mice and delays the appearance of
      mouse mammary tumors.
AB  - Human epithelial mucin (MUC1) is expressed by many carcinomas, including breast
      cancer cells. This breast cancer-associated antigen has been widely used for
      immunotherapy, despite the fact that cellular immune responses to MUC1 are
      impaired in breast cancer patients and MUC1 transgenic animals. Previously, we
      found that immunogenicity to MUC1 was also impaired in BALB/c mice injected with
      a mammary tumor cell line (410.4) expressing human MUC1. We suggested that one
      reason for its weak immunogenicity was the lack of expression of B7 molecules by
      410.4 cells. Recognition of antigenic epitopes in conjunction with MHCI/II by the
      T-cell receptor without co-stimulation by B7/CD28 association resulted in T-cell
      anergy. Therefore, we attempted to enhance protective anti-MUC1-specific immunity
      in mice using B7 co-stimulatory molecules as a component of the MUC1 vaccine. We
      also compared cell-based with DNA-based vaccination strategies. One group of mice
      was vaccinated with an irradiated, 410.4 syngeneic mammary tumor cell line co
      expressing human MUC1 and CD80 or CD86 co-stimulatory molecules, and a second
      group of mice was vaccinated with plasmids encoding MUC1 and CD80 or CD86. These
      mice along with appropriate controls were challenged with mammary tumor cell line
      4T1, which expresses MUC1. There were significant inhibition on rates of tumor
      growth and survival in mice vaccinated with irradiated 410.4/MUC1 cells co
      expressing either CD80 or CD86 molecules, compared to non-vaccinated animals. In
      addition, there were also significant delays in the appearance of measurable
      tumors and their growth in mice vaccinated by gene-gun immunization with plasmids
      encoding MUC1 and CD80 or CD86.

PMID- 14598883
TI  - Growth factor-dependent activation of the MAPK pathway in human pancreatic
      cancer: MEK/ERK and p38 MAP kinase interaction in uPA synthesis.
AB  - Increased expression of the hepatocyte growth factor (HGF) receptor (c-met) and
      urokinase type plasminogen (uPA) correlated with the development and metastasis
      of cancers. To investigate the role of HGF/c-met signaling on metastasis in
      cancer cells stimulated with HGF, we examined the effects of a specific MEK1
      inhibitor (PD98059) and a p38 MAP kinase inhibitor (SB203580) on HGF-induced uPA
      expression in pancreatic cancer cell lines, L3.6PL and IMIM-PC2. Pretreatment of
      PD98059 decreased HGF-mediated phosphorylation of extracellular receptor kinase
      (ERK), uPA secretion and expression of matrix metalloproteinases (MMP-2 and MMP
      9) in a dose-dependent manner. In contrast, SB203580 pretreatment increased HGF
      stimulated ERK phosphorylation, uPA secretion and expression of MMPs. SB203580
      also reversed the inhibition of HGF-mediated ERK activation and uPA secretion in
      the PD98059-pretreated cells. These results suggest that ERK activation by HGF
      might play important roles in the metastasis of pancreatic cancer and the p38
      MAPK pathway also involved in the HGF-mediated uPA secretion and metastasis by
      regulation of ERK pathway.

PMID- 14598884
TI  - Prediction of nodal spread of breast cancer by using artificial neural network
      based analyses of S100A4, nm23 and steroid receptor expression.
AB  - The expression of tumour promoter gene S100A4, metastasis suppressor gene nm23,
      oestrogen and progesterone receptors, and tumour grade and size have been
      investigated for their potential to predict breast cancer progression. The
      molecular and cellular data have been analysed using artificial neural networks
      to determine the potential of these markers to predict the presence of metastatic
      tumour in the regional lymph nodes. This study shows that tumour grade and size
      are poor predictors. The relative expression of S100A4 and nm23 genes is the
      single most effective predictor of nodal status. Inclusion of oestrogen- and
      progesterone-receptor status with tumour grade and size markers improves
      prediction; however, there may be some overlap between steroid receptors and
      molecular markers. This study also underscores the power of artificial neural
      network techniques to predict the potential of primary breast cancers to spread
      to axillary lymph nodes. This could aid the clinician in determining whether
      invasive procedures of axially node dissection can be obviated and whether
      conservative forms of treatment might be appropriate in the management of the
      patient.

PMID- 14598885
TI  - Selection of more aggressive variants of the gI101A human breast cancer cell
      line: a model for analyzing the metastatic phenotype of breast cancer.
AB  - In vivo models utilizing orthotopic injection of tumor cells into nude mice have
      proven valuable for the study of metastasis. However, breast cancers are among
      the more difficult of human tumors to grow in immunodeficient mice, with a
      relatively low tumor take. Fewer still develop spontaneous metastases. The
      injection of GI101A breast cancer cells into the mammary fatpad (mfp) produced
      lung metastases in 25% of tumor-bearing mice. Selecting cells from the lung
      metastases and recycling in vivo resulted in the isolation of a series of variant
      cell lines. These cell lines were tested for tumorigenicity and metastasis in
      nude mice following mfp injection compared with the original cell line, and in
      vitro expression of factors associated with the metastatic phenotype measured.
      The in vivo selected cell lines were more aggressive, with higher tumor take,
      faster local growth rate and increased incidence (> or = 85%) and extent of lung
      metastasis. However, the metastasis-selected variants showed no increases in
      expression of the growth factor receptors EGFR or HER-2, and the pro-angiogenic
      factors VEGF-A and IL-8. Immunohistochemistry of mfp tumors revealed no
      differences in microvessel density (counting CD-31 positive structures) and cell
      proliferation (PCNA-positive cells) comparing the GI101A line with selected
      variants. No TUNEL-positive cells were detected in the tumors of the metastasis
      derived variant, with a small number of cells undergoing apoptosis detected in
      sections of GI101A tumors. In vitro, the metastasis-derived variants were found
      to have a more robust expression of phosphorylated PKB/Akt, with or without EGF
      or serum stimulation, suggesting an association between Akt activation and
      metastatic ability. This new series of isogenic cell lines may be valuable for
      identifying molecular mechanisms involved in the metastatic progression of breast
      cancer.

PMID- 14598886
TI  - Cytoplasmic and/or nuclear staining of beta-catenin is associated with lung
      metastasis.
AB  - Beta-catenin is involved in cell motility in the extracellular matrix, and is
      expressed in normal and neoplastic mesenchymal cells. In order to clarify whether
      beta-catenin expression in the cytoplasm and/or nucleus is associated with a
      propensity for pulmonary metastasis in osteosarcoma, the LM8 murine osteosarcoma
      cell line with a high metastatic potential to the lung was compared with original
      Dunn cells in terms of the beta-catenin expression level. Both osteosarcoma cell
      lines lost membrane localization of beta-catenin. However, beta-catenin gene had
      no mutation in exon 3 by direct sequence analysis. A large number of LM8 cells
      showed diffuse cytoplasmic and/or nuclear staining of beta-catenin (30.8 per high
      power field (HPF)), while a much smaller number of Dunn cells showed expression
      of beta-catenin (7.7 per HPF). Cells with positive staining of beta-catenin were
      frequently seen at the invasive front and in intravenous tumor deposits within
      the metastatic lesions to the lung. Thus, LM8 cells express a larger amount of
      the beta-catenin protein than Dunn cells, as judged by immunoblot analysis. In
      five resected cases of pulmonary metastasis, translocation of beta-catenin to the
      cytoplasm and/or nucleus of osteosarcoma cells was detected, although seven
      primary osteosarcomas cells that did not metastasize for more than five years did
      not show beta-catenin expression. These data indicate that the cytoplasmic and/or
      nuclear staining of beta-catenin is a biological marker of metastatic potential
      of osteosarcoma to the lung.

PMID- 14598888
TI  - The metalloproteinase inhibitor TIMP-2 is down-regulated by androgens in LNCaP
      prostate carcinoma cells.
AB  - Tissue inhibitors of metalloproteinases (TIMPs) have been shown to perform
      several biological functions in tumor promotion, principally by their action of
      inhibiting matrix metalloproteinases (MMPs) at different steps of the metastatic
      process. In particular, TIMP-2 is involved in a functional complex with the
      membrane-type 1 (MT1) MMP to convert the secreted MMP-2 progelatinase into the
      fully active proteolytic enzyme. We used the human, androgen-sensitive prostate
      carcinoma cell line LNCaP in coculture with the human osteosarcoma cell line OHS
      to experimentally address the possibility of androgen-dependent regulatory
      effects on the functional MT1-MMP/TIMP-2/MMP-2 complex upon interaction between
      prostate carcinoma and osteoblastic cells in metastasis of prostate cancer to
      bone. In the LNCaP cells a gradual, time-dependent decline in TIMP-2 mRNA
      expression was observed in the presence of the synthetic androgen analogue R1881
      (100 nM), reaching approximately 25% of the control level after 48 h of
      incubation. Consistent with this, the accumulation of secreted TIMP-2 in media
      from R1881-treated cells was significantly inhibited already after 3 h. Neither
      MMP-2 gelatinolytic activity nor expression of MT1-MMP was detected in LNCaP
      cells. In contrast, the OHS cells showed membrane-associated MT1-MMP expression
      as well as MMP-2 secretion. However, R1881 treatment of the LNCaP/OHS coculture
      model did not seem to change the overall proteolytic activity of the MT1 
      MMP/TIMP-2/MMP-2 complex. Hormonal control of TIMP-2 expression in prostate
      carcinoma cells has not been previously reported, but whether such regulation has
      any functional role in the development of osteoblastic metastases in prostate
      cancer is still unclear.

PMID- 14598887
TI  - The role of Bcl-2 family members in the progression of cutaneous melanoma.
AB  - The overwhelming problem of cutaneous melanoma is chemoresistance. Subversion of
      the biochemical changes that lead to chemoresistance intersects the apoptosis
      pathways. The mitochondrion has been a focal point of this intersection for the
      development of therapeutic strategies aimed at reducing the progression of
      melanoma. The Bcl-2 family of apoptotic regulators is arguably the most pivotal
      component to this mitochondrial response. The shear number of studies conducted
      on the relationship between melanoma and Bcl-2 members prompted us to evaluate
      the literature available and discern some rational utility of the data. We have
      found that there are striking inconsistencies for the expression of Bcl-2 family
      proteins with melanoma progression, particularly for Bcl-2. Roughly one-third of
      the data suggests an increase in Bcl-2 expression with advancing melanoma, while
      another third suggests a decrease. Furthermore, the remaining third found on the
      whole, a detectable level of Bcl-2 in all tissues of melanocytic origin. These
      discrepancies are difficult to rectify in light of the apparent success of recent
      clinical trials utilizing Bcl-2 antisense strategies. The general consensus in
      the literature is that pro-apoptotic Bax is decreased with melanoma progression
      while anti-apoptotic Bcl-xL and Mcl-1 appear to increase with progression. We
      suggest that the biochemical techniques being used for analysis present too great
      of a heterogeneity, which could be mitigated with more standard procedures and
      reagents. Finally the utility of 'multi-specific' antisense tactics could be a
      more effective way of targeting advanced melanoma disease.

PMID- 14598889
TI  - Detection of disseminated tumor cells in nude mice with human gastric cancer.
AB  - Disseminated tumor cells (DTC) are a potential contributor to relapse of cancer.
      In the present study we developed a model for induction of disseminated tumor
      cells in nude mice, which can aid in the search for therapeutic approaches as
      well as improve our understanding of metastasizing gastric cancer. To detect DTC
      in blood and bone marrow we established a modified animal model of orthotopic
      transplantation. Two groups of nude mice were used for xenotransplantation of
      gastric cancer specimens. In group I tumor specimens originating from a gastric
      adenocarcinoma cell line were transplanted onto the stomach; in group II they
      were transplanted subcutaneously into both axillaries. Tumor growth, metastases
      and presence of DTC were compared in both groups. For detection of DTC a nested
      reverse transcriptase polymerase chain reaction (RT-PCR) for human cytokeratin
      (CK)-20 was performed on blood and bone marrow of all mice. Tumor growth occurred
      in both groups (9/10 animals in group I, 10/10 in group II) within 14 weeks. Only
      animals in group I developed local invasive tumor growth, stenosis of the stomach
      and distant metastases. Tumors in animals of group II grew with local
      displacement only and developed no metastases. There were no signals of CK-20
      detected in the blood in both groups. In group I, 5 of 9 animals had positive
      signals of human CK-20 in their bone marrow as a sign of DTC. In group II no DTC
      were detected in bone marrow. We conclude that orthotopic transplantation is a
      prerequisite for the development of DTC and metastasizing tumor growth in this
      modified gastric cancer model.

PMID- 14598890
TI  - Suppression by nimesulide of bombesin-enhanced peritoneal metastasis of
      intestinal adenocarcinomas induced by azoxymethane in Wistar rats.
AB  - The effects of the cyclooxygenase (COX)-2 inhibitor nimesulide on bombesin
      enhanced peritoneal metastasis of azoxymethane (AOM)-induced intestinal
      adenocarcinomas were investigated in male Wistar rats. From the beginning of the
      study, the rats were given 10 weekly s.c. injections of AOM (7.4 mg/kg body
      weight) and s.c. injections of bombesin (40 microg/kg body weight) every other
      day. From week 16, the rats were given chow pellets containing 200 ppm or 400 ppm
      nimesulide ad libitum until termination of the study at week 45. Nimesulide at
      the higher dose significantly decreased the incidence of bombesin-enhanced
      metastasis to the peritoneum at week 45, although its administration had little
      or no effect on the location, histologic type, depth of involvement or
      infiltrating growth patterns of the tumors. Nimesulide also significantly
      decreased the incidence of bombesin-enhanced lymphatic vessel invasion by
      adenocarcinomas. Finally, it also inhibited bombesin-induced matrix
      metalloproteinase (MMP)-9 and pro-MMP-9 inductions. Our findings indicate that
      nimesulide may inhibit cancer metastasis through inhibition of pro-MMP-9 and MMP
      9 inductions.

PMID- 14598891
TI  - Selective inhibition of cancer cell invasion by a geranylgeranyltransferase-I
      inhibitor.
AB  - A number of small GTPases are involved in cancer cell proliferation, migration
      and invasion. They need to be prenylated for full biological functions. We have
      recently reported that 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase
      inhibitors, which block the biosynthesis of farnesylpyrophosphate and
      geranylgeranylpyrophosphate, inhibit in vitro invasion of human pancreatic cancer
      cells. In the present study, we examined the effects of two selective inhibitors
      of prenylation, a farnesyltransferase inhibitor (FTI-277) and a
      geranylgeranyltransferase type I inhibitor (GGTI-298), on in vitro invasion of
      cancer cells in a modified Boyden chamber assay. The invasion of COLO 320DM human
      colon cancer cells was inhibited potently by HMG-CoA reductase inhibitor
      lovastatin and GGTI-298 but weakly by FTI-277. The treatment of cancer cells with
      GGTI-298 markedly caused RhoA to decrease in the membrane fraction and accumulate
      in the cytosolic fraction, whereas it had almost no effect on the translocation
      of Ras. FTI-277 markedly inhibited membrane localization of Ras, but its
      inhibitory effect on cancer cell invasion occurred only at doses that affected
      membrane localization of RhoA. FTI-277 and GGTI-298 decreased the growth
      potential of COLO 320DM cells, but the inhibitory effect of GGTI-298 was rather
      selective toward invasion in association with changes in cell morphology and RhoA
      localization. These results suggest that geranylgeranylation of RhoA by
      geranylgeranyltransferase type I is critical for cancer cell invasion, and
      inhibition of geranylgeranyltransferase type I activity should offer a novel
      approach to the treatment of invasion and metastasis of cancer cells resistant to
      farnesyltransferase inhibitors.

PMID- 14598894
TI  - Comparison between visual and computer-assisted analysis.

PMID- 14598899
TI  - Accurate plaque volume measurements in 3D reconstructed IVUS pullback sequences.

PMID- 14598895
TI  - Assessment of vasoreactivity using videodensitometry coronary angiography.
AB  - BACKGROUND: Previous studies demonstrated that the dysfunction of vasomotor tone
      (VT) is closely linked to the development of atherosclerosis and it is considered
      important in the very early stages of atherogenesis. Currently, the evaluation of
      VT relies on lumen changes in response to vasoactive stimuli using quantitative
      coronary angiography (QCA) based on geometric edge detection (ED). However, using
      ED for measuring lumen diameters is inherently associated with large
      uncertainties. Videodensitometry (VD) methods have important advantages over ED
      for QCA. The objective of this study was to investigate the reliability of VD and
      ED techniques in determining the effect of nitroglycerin (NTG) on cross-sectional
      area (CSA) and volume changes in a swine animal model for evaluating coronary
      vasoreactivity. METHODS AND RESULTS: Coronary angiography was performed on four
      anesthetized swine. CSA and volume were measured in the left anterior descending
      (LAD) coronary artery using VD before and after intracoronary injection of 0.3 mg
      of NTG. CSA was also calculated using standard QCA based on ED. The average CSA
      changes in the proximal, middle and distal branches measured using VD were 23.83%
      (+/-10.76%), 30.78% (+/-18.39%), and 27.34% (+/-36.53%), respectively. Similarly,
      the average CSA changes in the proximal, middle, and distal branches measured
      using ED were 15.02% (+/-36.38%), 22.02% (+/-26.12), and 38.00% (+/-48.31%),
      respectively. The average lumen volume change measured using VD was 29.79% (+/
      14.79%). In order to evaluate the relative reliability of the techniques. the
      significance of deviation (SOD) was calculated, which is the ratio of the change
      after NTG and the measurement error. The average SOD for CSA for all the branches
      based on VD and ED were 1.86 and 0.69, respectively. The SOD for volume
      measurement was 2.78. CONCLUSIONS: Lumen changes measured by VD showed
      substantial improvement in reliability when compared to the ED. Moreover, VD can
      be used to measure substantially smaller changes in lumen dimension in response
      to vasoactive stimuli than the standard QCA based on ED. Finally, VD allows the
      measurement of arterial volume, which is not possible with ED.

PMID- 14598897
TI  - The influence of premature ventricular contractions on left ventricular function
      in asymptomatic children without structural heart disease: an echocardiographic
      evaluation.
AB  - BACKGROUND: Isolated monomorphic premature ventricular contractions (PVCs) are
      not uncommon in the pediatric population. The degree of cardiac dysfunction
      caused by PVCs in children without structural heart disease is unknown. PURPOSE:
      To investigate the influence of PVCs on echocardiographic left ventricular (LV)
      systolic function in children without structural heart disease. METHODS: Forty
      asymptomatic children with isolated monomorphic PVCs without structural heart
      disease were selected. The median age was 6 years, range of 3-12 years. The
      following subgroups were compared: frequent vs. infrequent PVCs (> or < or =
      10/min); short vs. long coupling interval (RR'/RR ratio < or = or > 0.6); and
      short vs. long QT interval (QT < or = or > 400 ms). Using echocardiography the
      left ventricular ejection fraction (LVEF in percentage) and cardiac index (CI in
      L/min/m2) were measured for both normal sinus beats (SB-LVEF and CI), PVCs (PVC
      LVEF and CI) and the average LVEF and CI were calculated. All values were
      expressed as means +/- SD. RESULTS: In all children LV dimensions and the SB-LVEF
      and CI were within normal limits. The PVC-LVEF (48 +/- 5) and PVC-CI (1.57 +/-
      0.19) were significantly decreased and the average CI was 2.41 +/- 0.29. In 27
      pts with > 10 PVCs/min the average LVEF and CI decreased to 53 +/- 5 and 2.08 +/-
      0.24 respectively. In 16 pts with PVCs and a short coupling interval (RR'/RR < or
      = 0.6) the PVC-LVEF and PVC-CI was 43 +/- 0.03 and 1.50 +/- 0.14, which was
      significantly lower than in 24 pts with a long coupling interval (58 +/- 4, 1.88
      +/- 0.11). In 11 pts with a prolonged QT interval (> 400 ms) the PVC-LVEF and PVC
      CI was significantly lower than in the 29 children with a shorter QT interval, 41
      +/- 5 vs. 55 +/- 4 and 1.46 +/- 0.13 vs. 1.86 +/- 0.15 respectively (all p <
      0.01). CONCLUSION: In asymptomatic children with isolated monomorphic PVCs the
      average ejection fraction and cardiac output is markedly reduced if PVCs are
      frequent (> 10/min), have a short coupling interval or a prolonged QT interval.

PMID- 14598896
TI  - Registration of 3D CT angiography and cardiac MR images in coronary artery
      disease patients.
AB  - A method for the registration of 3D cardiac CT angiography (CTA) and magnetic
      resonance (MR) data sets based on their myocardial epicardial surfaces is
      introduced. The approach relies on temporally registered data sets obtained based
      on the electrocardiogram recorded during the CTA acquisition and the timing
      characteristics of the MR acquisition. The myocardial epicardial surfaces were
      identified in the reformatted CTA and MR data sets using a 3D semi-automated
      segmentation algorithm. This algorithm was implemented, evaluated on clinical
      data, and compared to a set of manual outlines during the course of this study.
      The registration of the CTA and MR data sets was based on the iterative closest
      point algorithm, which minimizes the distance between the surfaces defined by the
      epicardial outlines in each data set. The proposed technique was applied to data
      obtained from 11 patients with coronary artery disease. The CTA data was
      reformatted based on the registration results and the location of the MR imaging
      planes. The resulting CTA-MR image pairs were evaluated qualitatively by two
      experts, who graded the majority of the cases as either excellent or acceptable
      (11 of 11 cases for one reader, and 9 of 11 for the other). The results were
      evaluated quantitatively based on the distance between the registered epicardial
      surfaces. The quantitative measures indicated that the registered surfaces were
      within two pixels of one another (on average). The registration results were used
      to generate combined 3D renderings of information extracted from both data sets
      for visualization purposes.

PMID- 14598900
TI  - Myocardial ischemia assessed by Tc99m MIBI SPECT and left ventricle regional
      systolic and diastolic function evaluated by tissue Doppler echocardiography.
AB  - BACKGROUND: Tc99m MIBI single-photon emission computed tomography (SPECT) study
      facilitates the evaluation of the regional myocardial perfusion and tissue
      Doppler echocardiography imaging facilitates the quantitative assessment of the
      regional systolic and diastolic function of the myocardium. The aim of the study
      was an assessment of the correlation between regional rest myocardial perfusion
      defects and regional rest systolic and diastolic myocardial velocities in
      patients with ischemic heart disease (IHD). MATERIAL AND METHODS: In 40 IHD
      patients (33 men, 7 women) aged 43-74 years (mean 56 years) rest SPECT imaging
      with Tc99m MIBI and rest tissue Doppler examinations were performed. The control
      group consisted of 35 healthy sex and age matched pesons. The left ventricle was
      divided into 13 segments. The number of non-perfused segments in three myocardial
      perfusion regions (left anterior descending artery, circumflex artery, right
      coronary artery) was assessed in IHD patients. During tissue Doppler examination
      the maximal systolic and maximal early diastolic velocity of the myocardium in
      each segment were established in both examined groups. RESULTS: The systolic and
      diastolic myocardial velocities were significantly lower in IHD group as compared
      to control group. In the IHD group statistically significant decrease of systolic
      and diastolic velocities in relation to the number of non-perfused segments was
      found. In comparing the linear regression slopes for systolic and for diastolic
      myocardial velocities in terms of intensification of perfusion defects, a more
      pronounced decrease in diastolic velocity was encountered. CONCLUSIONS: Both
      systolic and diastolic myocardial velocities are decreased in the myocardial
      regions with perfusion defects, but the reduction of the diastolic velocity is
      higher than the reduction of the systolic velocities. Thus our results indicate a
      good correlation between the intensity of perfusion abnormalities and myocardial
      velocities. The levels of diastolic dysfunction is more pronounced than the level
      of systolic dysfunction in the ischemic myocardium.

PMID- 14598901
TI  - Tissue Doppler imaging for detection of myocardial ischemia: are we there yet?

PMID- 14598898
TI  - Three methods for accurate quantification of plaque volume in coronary arteries.
AB  - The coronary atherosclerotic process evolves to an occlusive disease that causes
      chronic angina and acute coronary syndromes, such as myocardial infarction and
      sudden death. An important milestone in the understanding of the atherosclerotic
      process is the development of tools for quantitative assessment of disease
      progression or regression. A new methodology to analyze the coronary vessel lumen
      and plaque morphology in 3-D is based on the fusion of intravascular ultrasound
      (IVUS) and biplane X-ray angiography, which results in a geometrically correct
      representation of coronary vessels. A comparison of three volume quantification
      methods: polytope, Watanabe, and Simpson's rule is reported for quantifying the
      amount of plaque accumulation. The three methods allow local estimation of plaque
      volume. To determine volumetric indices, the space between the luminal and
      adventitial surfaces is first subdivided and then each of the volume elements is
      considered individually to achieve volume quantification. Polyhedral volume
      elements are employed and the volume of every element is estimated by each of the
      three approaches. The volume quantification methods were validated in 314
      computer-generated shapes. All three methods are highly accurate, providing a
      mean error of 0.138 +/- 0.049%, 0.139 +/- 0.049%, and 0.832 +/- 0.203% for the
      polytope, Watanabe, and Simpson-rule methods, respectively. Nevertheless, the
      polytope and Watanabe methods are statistically significantly more accurate than
      the Simpson-rule approach (p < 0.001). The volumetric quantification methods were
      also tested using seven in vivo coronary arterial datasets from seven patients
      undergoing coronary angioplasty. While the polytope and Watanabe approaches are
      statistically significantly more accurate compared to the Simpson's rule method,
      accuracy of either of the tested method is sufficient for all practical purposes.
      Yet, the methods are not interchangeable and a single technique should be used in
      comparative volumetric studies.

PMID- 14598902
TI  - An approach to the three-dimensional display of left ventricular function and
      viability using MRI.
AB  - Cardiac MRI was performed in human volunteers to determine the magnitude of the
      misregistration (MSR) of cardiac landmarks due to variability in the diaphragm
      position for repeated breath-holds. Seven normal volunteers underwent MR imaging
      of the left ventricle (LV) to evaluate the magnitude of the endocardial centroid
      MSR. The MSR for a mid-ventricle short-axis image was 3.01 +/- 1.68 mm through
      plane and 4.16 +/- 1.62 mm in-plane. A second order polynomial fit through the LV
      centroid coordinates minimized the in-plane component of the MSR error. Short
      axis cine images, corrected for MSR, provided high-resolution 2D data from which
      an accurate anatomical model of the LV was generated. Anatomical landmarks were
      used to register parametric maps of myocardial perfusion and viability to the
      three-dimensional (3D) model, with the corresponding parameters displayed as
      color-encoded values on the endo- and epicardial surfaces of the LV. Registration
      of regional wall motion, perfusion and viability to the 3D model was performed
      for three patients with a history of cardiovascular disease. The proposed 3D
      reconstruction technique allows visualization in 3D of the LV anatomy, in
      combination with parametric mapping of its functional status.

PMID- 14598908
TI  - The influence of various carbohydrates on the feeding pattern of rats fed zinc
      deficient diets.
AB  - When dextrin, maltose, sucrose, glucose, and fructose were used as a source of
      carbohydrate in a diet, the food intake of rats fed either a Zn-adequate or Zn
      deficient diet was evaluated daily over 28 d. The average food intake of all
      groups of rats fed the Zn-deficient diet was significantly lower than that of the
      corresponding groups of Zn-adequate control rats. The food intake of the dextrin
      group was the highest under both Zn-deficient and Zn-adequate diets, and that of
      the fructose group was the lowest. All rats of the dextrin, maltose, sucrose,
      glucose, and fructose groups with the Zn-deficient status showed a characteristic
      cyclic variation in food intake and fitted well to a Cosinor curve. The values of
      the mesor, amplitude, and period of the food intake cycles showed significant
      differences among the groups. The higher intake of the glucose diet than the
      fructose diet of rats fed a Zn-deficient diet may be related to the different
      metabolisms of the carbohydrates used, from the comparison of the quantities
      consumed in the corresponding carbohydrates of Zn-adequate diets.

PMID- 14598903
TI  - Improved functional cardiac MR imaging using the intravascular contrast agent
      CLARISCAN.
AB  - PURPOSE: Using segmented k-space turbo gradient echo MR techniques (TGE) contrast
      between blood and myocardium is often reduced in long axis views due to reduced
      in plane spin-refreshment, particularly in patients with low ejection fraction.
      The application of an intravascular contrast agent (CA) may improve endocardial
      border delineation. MATERIALS AND METHODS: In 15 patients cardiac cine loops in
      two long axis and two short axis views were acquired during breath hold using a
      TGE sequence without and with increasing doses of CA (0.75, 2.0, 5.0 mg Fe/kg).
      Two independent observers evaluated left ventricular function (LVEF, modified
      Simpson's rule) and assigned a visual score (range: 0 = 'not visualized' to 6 =
      'excellent visualization') for endocardial border delineation. Signal- and
      contrast-to-noise ratios (SNR; CNR) were determined. RESULTS: Endocardial border
      delineation score for TGE was 1.7 +/- 0.6 and 3.9 +/- 0.6**, 4.4 +/- 0.5**, 4.6
      +/- 0.4** for 0.75, 2.0, 5.0 mg Fe/kg of CA, respectively (**p < 0.01 vs. TGE).
      SNR of blood increased significantly with any dose of CA with a mild drop of
      myocardial SNR resulting in a significant increase of CNR blood/myocardium. The
      maximum effect with 2.0 mg Fe/kg was a >2-fold CNR increase. Inter- and
      intraobserver variability assessed according to the method of Bland-Altmann was
      reduced at 2.0 mg Fe/kg for determination of LVEF and reached statistical
      significance for LVEF <50%. CONCLUSION: Intravascular CA increased CNR between
      blood and myocardium by a factor >2 and significantly improved the determination
      of cardiac volumes. The benefit in accuracy was most for patients with left
      ventricular ejection fraction <50%.

PMID- 14598909
TI  - Development of iron deficiency decreases zinc requirement of rats.
AB  - Effects of the development of Fe deficiency on changes in Fe and Zn metabolism
      and its possible interactions with dietary Zn were determined. Adequate (25
      microg/g) and marginally deficient (5 microg/g) Zn diets containing a sufficient
      (40 microg/g) dietary Fe levels were fed for 2 wk. Thereafter, both dietary Zn
      groups were fed an Fe-deficient (2.2 microg/g) diet for 4 wk. It was found that
      the effects of an Fe-deficient diet began to occur 7 and 14 d after feeding the
      Fe-deficient diet. At this time, tissue Fe concentrations were depleted and rats
      were unable to maintain hemoglobin levels. The Fe-deficient diet also induced an
      immediate fall in plasma Fe concentration, transferrin saturation, and apparent
      Fe absorption, while the concentrations of liver cytochrome c increased as Fe
      deficiency developed. Decreases in liver and spleen Fe levels, as well as the
      activities of blood and bone marrow aminolevulinic acid dehydratase (ALA-D, EC
      4.2.1.24) were observed 3, 7, and 14 d after feeding the Fe-deficient diet, and
      thereafter they were increased. On the other hand, the activity of plasma
      alkaline phosphatase (ALK-P, EC 3.1.3.1) decreased continuously as Fe deficiency
      progressed. With severe development of Fe deficiency, rats fed the Zn-adequate
      diet had increased levels of Zn concentration in the plasma, liver, spleen,
      kidney, and femur, whereas apparent Zn absorption was decreased. The decrease in
      apparent Zn absorption and the increase in tissue Zn concentration of rats might
      be related to the lowered Zn requirement, which is associated with the depressed
      Zn metabolism caused by feeding Fe-deficient diets.

PMID- 14598893
TI  - End-diastolic and end-systolic volume from the left ventricular angiogram: how
      accurate is visual frame selection? Comparison between visual and semi-automated
      comnputer-assisted analysis.
AB  - BACKGROUND: End-diastolic (ED), end-systolic (ES) left ventricular (LV) volumes
      and LV ejection fraction (LVEF) are important parameters for clinical decision
      making in heart disease. In clinical practice the frames from cine-angiography
      with the largest and smallest opacified LV areas are visually selected and the
      endocardial borders traced as LVED and LVES contours, respectively. We compared
      the accuracy of this visual method using two frames with a semi-automated
      computer assisted frame-by-frame analysis of the complete opacified cardiac
      cycles. METHODS AND RESULTS: In 17 patients a biplane LV cine-angiogram was
      obtained at 25 frames/s. Complete frame-by-frame analysis was performed using
      semi-automatic border detection software. Experienced independent observers
      visually selected and manually traced LVED and LVES in the so-called visually
      assessed two-frame method in a consensus meeting. LV volumes were calculated by
      the area-length method. Mean LVEDV, LVESV and LVEF were 133 +/- 57, 56 +/- 40 ml
      and 61 +/- 16%, respectively, for the visually assessed two-frame method, and 117
      +/- 49, 53 +/- 33 ml and 60 +/- 13%, respectively, for the semi-automated
      computer assisted frame-by-frame method. LVEDV was significantly higher in the
      visually assessed two-frame method (p < 0.01). Linear regression analysis showed
      an excellent correlation between semi-automated computer-assisted frame-by-frame
      and the visually assessed two-frame LVEDV (y = 1.2x - 2.9; r2 = 0.98), LVESV (y =
      1.2x - 8.2; r2 = 0.97) and good linear correlation for LVEF (p = 1.2x - 3.6; r2 =
      0.82). Bland-Altman analysis showed respectively a bias of 16.4, 2.4 ml and 5.0%
      with overall wide limits of agreement (-6.6 and 39.4 ml; -16.6 and 21.4 ml; -9.0%
      and 19.1%). CONCLUSION: Correlation is excellent when visually assessed LVED and
      LVES are compared with a semi-automated computer assisted frame-by-frame
      analysis. However, the visually assessed two-frame method tends to overestimate
      the volumes obtained by semi-automated computer-assisted frame-by-frame analysis,
      especially for LVEDV, indicating that visual selection will yield a higher LVEF,
      which may influence clinical decision making.

PMID- 14598905
TI  - ECG-gated multislice spiral computed tomography to clarify lesion severity in a
      case of left main stenosis. Multislice spiral computed tomography to clarify
      lesion severity.
AB  - This case report describes the use of retrospectively ECG-gated multislice spiral
      computed tomography (MSCT) for evaluation of lesion severity in a patient with
      relevant left main stenosis by visual analysis of the coronary angiogram. For
      further diagnostic evaluation the patient underwent intravascular ultrasound
      (IVUS) imaging, which showed a maximal 30% area stenosis, and MSCT, which
      demonstrated a maximal 48% area stenosis. MSCT was useful in this case to defer
      cardiac surgery and might be used as a noninvasive alternative to IVUS imaging in
      case of doubtful lesion severity.

PMID- 14598907
TI  - Gallic acid, an antioxidant, exhibits antiapoptotic potential in normal human
      lymphocytes: A Bcl-2 independent mechanism.
AB  - Oxidative stress, produced as a consequence of normal metabolism or induced by
      extraneous stimuli, has been proved to be a mediator of cell death. The inherent
      antioxidant defense system and exogenous antioxidants can help the body to combat
      this oxidative stress-induced cell death. In this study, we explored the
      antiapoptotic potential of gallic acid, a dietary phenolic having antioxidative
      and anticarcinogenic properties, in normal human peripheral blood lymphocytes
      (PBLs). Incubation of PBLs with 100 microM H2O2 for 1.5-2.0 h induced
      phosphatidyl serine externalisation, lipid peroxidation and high molecular weight
      DNA fragmentation. Pretreatment of lymphocytes with gallic acid for 18 h could
      effectively inhibit lipid peroxidation and apoptosis induced by oxidative stress.
      Treatment of PBLs with gallic acid failed to induce any change in the expression
      of Bcl-2, an antiapoptotic protein. It seems that the protection provided by
      gallic acid was due to its direct action in the scavenging of free radicals as it
      was found to be a stronger antiradical than trolox, a water- soluble analogue of
      vitamin E.

PMID- 14598892
TI  - Use of RNA interference to inhibit integrin (alpha6beta4)-mediated invasion and
      migration of breast carcinoma cells.
AB  - The application of small interfering RNA (siRNA) oligonucleotides to silence gene
      expression has profound implications for the intervention of human diseases
      including cancer. Using this technique, we explored the possibility that the
      alpha6beta4 integrin, a laminin adhesion receptor with a recognized role in the
      invasive phenotype of many carcinomas, represents a potential therapeutic target
      to inhibit the migration and invasion of carcinoma cells. We found that siRNA
      oligonucleotides targeted to either subunit of the alpha6beta4 integrin reduced
      cell surface expression of this integrin and resulted in decreased invasion of
      MDA-MB-231 breast carcinoma cells. Interestingly, reduced alpha6beta4 expression
      also promoted decreased migration on non-laminin substrata indicating that this
      integrin can function in a ligand-independent manner. In addition, the absence of
      beta4 expression in these cells augmented the formation of alpha6beta1
      heterodimers and increased adhesion to laminin-1. Taken together, these results
      substantiate the importance of the alpha6beta4 integrin in invasion and migration
      that has been demonstrated previously by expression of the beta4 subunit in beta4
      deficient cell lines and by function blocking antibodies. Furthermore, these data
      suggest that the utilization of siRNA oligonucleotides to reduce the expression
      of the alpha6beta4 integrin may be a useful approach to prevent carcinoma cell
      progression.

PMID- 14598906
TI  - Antioxidant activities of natural vitamin E formulations.
AB  - The antioxidant activities of natural d-alpha-tocopherol, mixed tocopherols and
      tocotrienols, and formulations comprising all forms of vitamin E, providing 400
      IU, were determined employing an improved oxygen radical absorbance capacity
      (ORAC) assay using fluorescein (FL) as the fluorescent probe, randomly methylated
      beta-cyclodextrin (RMCD), 2,2'-azobis(2-amidino-propane)dihydrochloride (AAPH) as
      the peroxyl radical generator, and Trolox as the standard in 75 mM phosphate
      buffer. The antioxidant activities, expressed in micromol Trolox equivalent per
      gram, of d-alpha-tocopherol (87%), mixed tocopherols (70%), and tocotrienols
      (30%) were found to be 1,293, 1,948, and 1,229, respectively. Some of the vitamin
      E formulations showed antioxidant activities superior to d-alpha-tocopherol.

PMID- 14598911
TI  - Postprandial changes in portal venous free amino acids and insulin/glucagon
      ratios as the result of protein over-intake are not directly linked to serine
      dehydratase induction in rat liver irrespective of age.
AB  - The activity of hepatic serine dehydratase (SDH) increases in tandem with its
      gene expression when the intake of protein greatly exceeds protein requirements.
      The actual conditions of plasma free amino acids and pancreatic hormones in
      weanling and mature rats when fed SDH-inducible and non-inducible diets were
      examined in relation to incentive factors to secure high SDH activity from a
      physiological standpoint. Both weanling and mature groups differing in protein
      requirements were allowed free access to respective diets diverse in protein
      content (i.e. 25% or 50% casein diet for the former and 6% or 25% casein diet for
      the latter) during the dark cycle (lights-out) over a period of 1 wk. Despite the
      difference in protein intake among these groups, there were no conspicuous
      changes in the plasma concentration of the urea or total or essential amino
      acids. Therefore, it appears that the individual amino acids did not up regulate
      the gene and function expressions of SDH merely by their superabundance and
      subsequent disposal. Portal venous insulin concentration was far higher in mature
      groups than in weanling groups, although there was little difference between the
      two groups of the same age in terms of insulin or glucagon concentration and
      their ratio in abdominal vena cava blood. Accordingly, it follows that the SDH
      gene undergoes transcriptional regulation through a combined signaling pathway
      triggered by perceiving surplus protein nutrition as a whole rather than directly
      through already-known plasma constituents such as free amino acids or pancreatic
      hormones in the circulatory system.

PMID- 14598904
TI  - Cardiac magnetic resonance simultaneously evaluates Leriche syndrome and prior
      inferior myocardial infarction.
AB  - A woman with ECG findings suspicious of ischemic heart disease was referred for
      coronary angiography, but this was impossible via the left or right iliac
      arteries because of total occlusion. Cardiovascular magnetic resonance (CMR) was
      performed to assess the anatomy of the abdominal aorta, cardiac function, and
      myocardial viability in a single study. Contrast-enhanced magnetic resonance
      angiography (CE-MRA) revealed Leriche syndrome resulting from occlusion of the
      infrarenal aorta and common iliac arteries. Delayed contrast enhancement
      indicated full thickness nonviable myocardial infarction. Coronary angiography
      via the right radial artery revealed proximal occlusion of the right coronary
      artery. This is the first case that illustrates the value of CMR as a time-saving
      non-invasive imaging technique with the ability to do in a single study what
      might otherwise take two studies.

PMID- 14598912
TI  - Menatetrenone ameliorates reduction in bone mineral density and bone strength in
      sciatic neurectomized rats.
AB  - Vitamin K2 (menaquinone) acts on the bone metabolism. Menatetrenon (MK-4) is a
      vitamin K2 homologue that has been used as a therapeutic agent for osteoporosis
      in Japan. Rat models of immobilization induced by sciatic neurectomy are
      characterized by transiently increased bone resorption and sustained reduction in
      bone formation. Using such a rat model, we investigated the efficacy of MK-4 on
      bone loss. Male Sprague-Dawley rats were subjected to unilateral sciatic
      neurectomy and administered MK-4 for 28 d beginning day 21 after operation. The
      effect of MK-4 on the immobilized bone was assessed by measuring the bone mineral
      density of the femur, breaking force of the femoral diaphysis, and bone
      histomorphometry in tibial diaphysis. The BMD on both the femoral distal
      metaphysis and diaphysis was reduced by sciatic neurectomy. The administration of
      MK-4 ameliorated this reduction in a dose-dependent manner. The administration of
      30 mg/kg MK-4 ameliorated the reduction in bone strength. An improvement in bone
      formation was observed following the administration of MK-4. These results
      suggest that MK-4 has a therapeutic potential for immobilization-induced
      osteopenia.

PMID- 14598910
TI  - Adaptation of skeletal muscle characteristics to a high-fat diet in rats with
      different intra-abdominal-obesity susceptibilities.
AB  - The purpose of the present study was to investigate the relationship between
      intra-abdominal-obesity susceptibility and the adaptation of skeletal muscle
      metabolic and histochemical characteristics when fed a high-fat diet (HFD) for a
      short period of time. Twenty-four male Wistar rats were fed a HFD (39.7% calories
      of fat) for 5 wk. After the 5-wk dietary period, the rats were sacrificed and
      divided into intra-abdominal-obesity-prone (OP) or obesity-resistant (OR) groups
      according to the total intra-abdominal fat pads (epididymal, mesenteric, and
      perirenal) weights. A superficial portion of the Muscle (M.) gastrocnemius tissue
      obtained from 2 groups before and after feeding the HFD were analyzed to
      determine their hexokinase (HK), (beta-hydroxyacyl CoA dehydrogenase (beta-HAD),
      and citrate synthase (CS) activities. Muscle fiber composition and capillary
      density were examined in the deep portion of the M. gastrocnemius, soleus, and
      extensor digitorum longus (EDL) gained after the HFD. While the OP group had more
      intra-abdominal fat pads and a heavier final body weight than the OR group, there
      was no significant difference in the energy intake between the two. Due to the
      HFD, the OP group showed significant increases in beta-HAD and CS activities,
      while the OR group did not. Change of beta-HAD activity by HFD in the OP group
      was significantly greater than that in the OR group. The ratio of fat oxidation,
      expressed as beta-HAD/CS, significantly increased in the OP group, but not in the
      OR group. No differences were found in either the muscle fiber composition or
      capillarization. These results suggest that intra-abdominal-obesity-susceptive
      rats may have a higher adaptation degree in muscle oxidative enzyme activities as
      characteristic in the early stage of intra-abdominal adipose accumulation.

PMID- 14598915
TI  - Antioxidant effects of phytosterol and its components.
AB  - Phytosterol contained in vegetable oils is known to exert a hypocholesterolemic
      function. In the present study, the antioxidant effects of phytosterol and its
      components, beta-sitosterol, stigmasterol, and campesterol, against lipid
      peroxidation were examined by making a comparison with 2,2,5,7,8-pentamethyl-6
      chromanol (PMC). It was found that these compounds exerted antioxidant effects on
      the oxidation of methyl linoleate in solution and its effect decreased in the
      order of: PMC >> phytosterol approximately campesterol approximately beta
      sitosterol > stigmasterol. Phytosterol also suppressed the oxidation and
      consumption of alpha-tocopherol in beta-linoleoyl-gamma-palmitoyl
      phosphatidylcholine (PLPC) liposomal membranes, the effects being more
      significant than dimyristoyl PC of the same concentration. Stigmasterol
      accelerated the oxidation of both methyl linoleate in solution and PLPC liposomal
      membranes in aqueous dispersions, which was ascribed to the oxidation of allylic
      hydrogens at the 21- and 24-positions. Taken together, the present study shows
      that phytosterol chemically acts as an antioxidant, a modest radical scavenger,
      and physically as a stabilizer in the membranes.

PMID- 14598917
TI  - Correlation between serum retinol and alpha-tocopherol levels in centenarians.
AB  - Recent evidence indicates that longevity may be achieved when efficient defence
      mechanisms against oxidative stress, infections, neoplasia, and cardiovascular
      events are preserved. Centenarians represent an example of "successful aging,"
      and the aim of this study was to evaluate serum levels of vitamins A and E, which
      represent two important nonenzymatic antioxidant defence systems, and their
      correlation in 16 healthy centenarians and two groups of control subjects.
      Centenarians showed normal values of retinol (450.9 +/- 240.3 ng/mL) and alpha
      tocopherol (9220.2 +/- 3410.9 ng/mL). Moreover, a significant direct correlation
      between the two vitamins was observed in centenarians (Rho = 0.715, p = 0.0056),
      such as in younger control subjects (Rho = 0.618, p = 0.0168), but not in older
      control subjects. We assume that the preservation of normal values and the
      correlation between vitamin A and E concentrations protects centenarians against
      oxidative stress and contributes to their extreme longevity.

PMID- 14598913
TI  - Activity diary method for predicting energy expenditure as evaluated by a whole
      body indirect human calorimeter.
AB  - In comparison with the energy expenditure determined by a whole-body indirect
      human calorimeter, which provides 24-h energy expenditure (TEE) with high
      precision and accuracy, the accuracy of predicting energy expenditure (EE) using
      an activity diary (AD) method was evaluated. Observed and predicted basal
      metabolic rate (BMR) as well as literature values for typical physical activities
      were used for TEE prediction. The effect of the number of recorded items in the
      activity diary on the accuracy of TEE was also examined. Additionally, predicted
      EE was divided into sleeping, exercise, and sedentary EE to evaluate the
      estimation errors in the AD method. Subjects were 20- to 69-y-old Japanese women
      (n = 20) and men (n= 21). Predicted TEE based on the AD was derived by applying
      the observed or predicted BMR to literature values for physical activities; i.e.,
      relative metabolic rate (R.M.R.), physical activity ratio (PAR), and metabolic
      equivalent (MET). The BMR value observed for each subject was obtained by
      indirect calorimetry using a Douglas bag. The BMR for the subject was also
      estimated from the predictive equations in the 6th revision of the Recommended
      Dietary Allowances for the Japanese (1999). The correlations between observed and
      predicted TEE appeared stronger when using observed BMR than those using
      predicted BMR. Although the difference of mean values between the predicted and
      observed TEE was small, the limits of agreement between the predicted and
      observed TEE were around +/- 400 kcal. Predicted EE, excluding the time periods
      for exercise and rest laying down when determining BMR, showed similar results to
      those of TEE. Furthermore, the number of recorded items in the AD was not
      significantly correlated to the accuracy of the predicted TEE (r = -0.03). These
      findings indicate that the predicted TEE of the AD using observed or predicted
      BMR and literature values is favorably comparable to observed TEE using a whole
      body human calorimeter on a group basis; however, its use as a proxy measure of
      TEE or EE on an individual basis may be limited.

PMID- 14598914
TI  - Dietary sesame lignans decrease lipid peroxidation in rats fed docosahexaenoic
      acid.
AB  - We have previously reported that dietary sesamin and sesaminol, major lignans of
      sesame seed, elevate the alpha-tocopherol concentration and decrease the
      thiobarbituric acid reactive substance (TBARS) concentration in the plasma and
      liver of rats. In this study, the effects of dietary sesamin and sesaminol on the
      lipid peroxidation in the plasma and tissues of rats fed docosahexaenoic acid
      (DHA, 22:6 n-3) were examined. Male Wistar rats (4-wk-old) were divided into the
      following six experimental groups: control group, fed a basal diet: sesamin
      group, fed a diet with sesamin (2 g/kg); sesaminol group, fed a diet with
      sesaminol (2 g/kg); DHA group, fed a diet containing DHA (5 g/kg); DHA + sesamin
      group, fed a diet containing DHA with sesamin; and DHA + sesaminol group, fed a
      diet containing DHA with sesaminol. Each diet contained either 0.01 or 0.05 g D
      alpha-tocopherol/kg, and the rats were fed the respective experimental diet for 5
      wk. The dietary DHA elevated the TBARS concentration and also increased the red
      blood-cell hemolysis induced by the dialuric acid. The dietary sesamin and
      sesaminol lowered the TBARS concentrations and decreased the red blood hemolysis.
      The dietary sesamin and sesaminol elevated the alpha-tocopherol concentrations in
      the plasma, liver, and brain of the rats fed a diet with or without DHA. These
      results suggest that dietary sesame lignans decrease lipid peroxidation as a
      result of elevating the alpha-tocopherol concentration in rats fed DHA.

PMID- 14598918
TI  - The assay of ascorbic acid in serum is not affected by physiological
      concentrations of transferrin and hemoglobin.
AB  - Transferrin and hemoglobin have been reported to oxidize L-ascorbic acid (AA) in
      vitro. The aim of this study was to determine whether or not physiological
      concentrations of serum transferrin (reference range 22-45 micromol/L) and
      hemoglobin (reference range 0-3.0 micromol/L) interfer with the measurement of AA
      in the serum. Transferrin (33 to 41 micromol/L) and hemoglobin (1.9 micromol/L)
      added to freshly pooled serum significantly decreased measured AA in the serum (p
      < 0.05). However, we found that the magnitude of the decrease in AA due to
      transferrin at concentrations within the reference range or up to 80 micromol/L
      was inconsequential, and had no clinical importance in diagnosing a low AA
      concentration. Hemoglobin at concentrations within the reference range had little
      affect on the serum AA measurement. However, when serum specimens were stored at
      4 degrees C for more than 1.5 h, the magnitude of the decrease in AA due to
      hemoglobin at physiological concentrations may cause a misleading clinical
      diagnostic evaluation of low AA concentration.

PMID- 14598916
TI  - Resistant starches of beans reduce the serum cholesterol concentration in rats.
AB  - We examined the effects of the resistant starches of adzuki (Vigna angularis),
      kintoki (Phaseolus vulgaris, variety), and tebou (P. vulgaris, variety) beans on
      the lipid metabolism in rats. Rats were fed a cholesterol-free diet with 25 g of
      cornstarch (CS)/100 g diet, 25 g of adzuki starch (AS)/100 g diet, 25 g of
      kintoki starch (KS)/100 g diet, or 25 g of tebou starch (TS)/100 g diet for 4 wk.
      The cecal contents in the TS group were significantly higher than those in the CS
      and KS groups. There were no significant differences in body weight or food
      intake among the groups. The relative liver weight in the CS group was
      significantly greater than that of the AS, KS, and TS groups. The serum total
      cholesterol, VLDL+IDL+LDL-cholesterol, and triglyceride concentrations in the AS,
      KS, and TS groups were significantly lower than those in the CS group throughout
      the feeding period. Though the total hepatic cholesterol concentration in the TS
      group was significantly higher than that in the KS group, there were no
      significant differences between the CS and other starch groups. The cecal pH
      value in the CS group was significantly higher than that of the bean starch
      groups. The cecal butyric acid concentrations in the AS, KS, and TS groups were
      significantly higher than that in the CS group, and the cecal total short-chain
      fatty acid (SCFA) concentrations in the AS and TS groups were significantly
      higher than those of the CS group. The fecal cholesterol excretion of the AS, KS,
      and TS groups were significantly higher than that in the CS group. The fecal
      coprostanol excretion in the AS group was significantly higher than that in the
      CS group. There was a negative correlation between the serum VLDL+IDL+LDL
      cholesterol concentration and fecal neutral steroid excretion (r = -0.664, p <
      0.001) in the present experiment. Furthermore, the cecal total SCFA concentration
      was negatively correlated with the serum VLDL+IDL+LDL-cholesterol concentration
      (r = -0.665, p < 0.001) and positively correlated with fecal neutral steroid
      excretion (r = 0.481, p < 0.05). The cecal butyric acid level was also negatively
      correlated with the serum VLDL+IDL+LDL-cholesterol concentration (r = -0.609, p <
      0.01) and positively correlated with fecal neutral steroid excretion (r = 0.658,
      p < 0.001). The results suggest that AS, KS, and TS elevate cecal SCFA
      concentration, in particular butyric acid concentration, and fecal neutral sterol
      excretion, and lower the serum total cholesterol level.

PMID- 14598919
TI  - Efficacy of dietary aloe vera supplementation on hepatic cholesterol and
      oxidative status in aged rats.
AB  - In the current study, we show the anti-oxidative and hypocholesterol effects of
      aloe vera in the liver. Male specific pathogen-free (SPF) Fischer 344 rats were
      randomly assigned to one of four groups: Group A (control) was fed test chow
      without aloe supplementation; Group B was fed a diet containing a 1% (per weight
      basis) freeze-dried aloe filet; Group C was fed a diet containing a 1% (per
      weight basis) charcoal-processed, freeze-dried aloe filet; and Group D was fed a
      diet containing a charcoal-processed freeze-dried, whole leaf aloe (0.02% per
      weight basis) in the drinking water. Our results show that a life-long intake of
      aloe had superior anti-oxidative action against lipid peroxidation in vivo, as
      indicated by reduced levels of hepatic phosphatidylcholine hydroperoxide.
      Additional anti-oxidative action was evidenced by enhanced superoxide dismutase
      (SOD) and catalase activity in groups B and C. Furthermore, our study revealed
      that hepatic cholesterol significantly increased in the control group during
      aging in contrast to the aloe-supplemented groups, which showed approximately 30%
      lower cholesterol levels, thereby an effective hypocholesteremic efficacy. In
      this report, we suggest that life-long dietary aloe supplementation suppresses
      free radical-induced oxidative damage and age-related increases in hepatic
      cholesterol.

PMID- 14598920
TI  - Bacteriocidal activity of garlic powder against Bacillus anthracis.
AB  - The antibacterial activity of garlic powder was examined against Bacillus
      anthracis using agar plate cultivation and test tube methods. On the agar plate
      test, 1-5% garlic powder inhibited the growth of B. anthracis and Escherichia
      coli O157 used as references. A 1% water solution of garlic powder in the test
      tube method killed B. anthracis at 10(7) cfu/mL within 3 h of treatment at room
      temperature. A number of intestinal bacteria in a BALB/c mouse decreased after
      the oral administration of 1 mL of 1%, garlic powder solution once a day for 3 d.
      These results suggest that the oral administration of garlic powder is effective
      against pathogenic bacteria invasion into the intestine as an infection.

PMID- 14598921
TI  - Nonresponse research--an underdeveloped field in epidemiology.

PMID- 14598922
TI  - Apportioning causes, targeting populations and predicting risks: population
      attributable fractions.

PMID- 14598923
TI  - Calculation of fractions of lung cancer incidence attributable to occupational
      exposure to asbestos and combustion products in Stockholm, Sweden.
AB  - In a population-based case-referent study of lung cancer we wanted to estimate
      the over-all influence on the lung cancer incidence from several occupational
      exposures. Standard methods to do this are based on addition of separately
      estimated attributable fractions (AFs) by rather complex formulas. Although a
      simple and valid method for direct estimation of summary effects was published in
      1990, it is not well known and has rarely been used. We here describe the method
      and apply it to the data from the case-referent study. The AF for withdrawal of
      occupational exposure to both asbestos and combustion products were nearly
      identical regardless of if it was calculated by an algorithm for summation of AF
      for the exposure factors separately (6.90%), by a bootstrap method (6.89%, 95%
      confidence interval, CI: 3.69, 10.04), or by the simple 'dichotomization'-method
      (6.88%, 95%CI: 3.81, 9.84). The method is very easy to apply to population-based
      case-referent studies analyzed by logistic regression.

PMID- 14598924
TI  - The effect of conducting a lottery on questionnaire response rates: a randomised
      controlled trial.
AB  - AIM: To study the effect of a lottery incentive on questionnaire response rate.
      MATERIAL AND METHODS: In Copenhagen County, Denmark, a random sample of 2543 men
      and women between the ages of 19 and 60 were randomised into a control group and
      an intervention group. Both groups were contacted by mail and asked to complete a
      questionnaire on sociodemografic characteristics, self-rated health and self
      reported physical activity level. The intervention group was offered
      participation in a small lottery for returning the questionnaire. No incentive
      was offered to the control group. MAIN RESULTS: The final response rate for the
      control group was 60.4 and 63.4% for the intervention group. Although the
      response rate was significantly higher in the intervention group after 2 and 3
      weeks, the difference in the final response rate between groups was not
      statistically significant (p = 0.12). There was no statistically significant
      difference between groups in sociodemografic characteristics, self-rated health
      or self-reported physical activity level. CONCLUSION: A lottery incentive had no
      significant effect on the overall response rate, but may have contributed to a
      quicker response. Furthermore a lottery incentive did not seem to alter the
      selection of respondents.

PMID- 14598925
TI  - Seasonal variation in consumption and plasma concentrations of fatty acids in
      Japanese female dietitians.
AB  - OBJECTIVE: To study seasonal variation in intake and plasma concentrations of
      fatty acids (FAs) in Japanese female dietitians. SUBJECTS AND METHODS: We
      assessed consumption of FAs based on four season 7 consecutive day weighed diet
      records from 71 Japanese female dietitians in 1996-1997. Using overnight fasting
      venous blood, plasma concentrations of FAs were analyzed by gas chromatography.
      Seasonal variation in consumption and plasma concentrations was examined by ANOVA
      for repeated values, followed by Tukey's multiple t-test. We calculated
      Spearman's partial rank correlation coefficients (CCs) between intake and plasma
      concentrations of FAs. Furthermore, we computed inter-seasonal Spearman's partial
      rank CCs for consumption and plasma concentrations of FAs. RESULTS: Statistically
      significant seasonal differences were observed in consumption for most FAs,
      except for myristic acid, monounsaturated FAs, oleic acid, n-6 polyunsaturated
      FAs (PUFAs), linoleic acid, gamma-linolenic acid, alpha-linolenic acid,
      PUFAs/saturated FAs, and n-6 PUFAs/n-3 PUFAs, and for most plasma concentrations,
      except for stearic acid, gamma-linolenic acid, n-3 PUFAs, alpha-linolenic acid,
      eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and n-3 highly
      unsaturated FAs (HUFAs). However, statistically significant Spearman's partial
      rank CCs between intake and plasma concentrations were observed for EPA, DHA, n-3
      HUFAs, n-6 PUFAs/n-3 PUFAs and n-6 PUFAs/n-3 HUFAs for almost all seasons.
      CONCLUSIONS: Seasonal variation exists in consumption and plasma concentrations
      of FAs, so that this should be taken into account in epidemiological analyses,
      including case-control and cohort studies.

PMID- 14598926
TI  - Body composition, ethnicity and alcohol consumption as determinants for the
      development of blood pressure in a birth cohort of young middle-aged men.
AB  - AIM: To investigate the development of blood pressure (BP) determinants over a
      period of 6 years in a birth cohort of middle-aged Swedish men. METHODS: Men born
      1953 and 1954 living in Helsingborg, Southern Sweden, were surveyed at 37, 40 and
      43 years of age. Baseline participation rate was 68% (n = 991). S-Cholesterol,
      HDL-Cholesterol, systolic and diastolic blood pressure (SBP and DBP) and
      anthropomorphic measurements were collected and a questionnaire covering
      ethnicity, smoking, leisure time physical activity (LTPA) and alcohol consumption
      was completed. RESULTS: At these surveys, SBP means were: 131, 132, 135 mm Hg and
      DBP were 83, 83 and 85 mm Hg respectively. Body mass index (BMI), waist hip ratio
      (WHR), S-Cholesterol and alcohol consumption consistently showed cross-sectional
      positive associations with SBP and DBP. One mmol/L higher S-Cholesterol at
      baseline predicted an increase in SBP by 1.16 mm Hg (confidence interval, CI:
      0.25; 2.07) over 6 years. At age 40, there was a 4.4 mm Hg (p < 0.020) difference
      in SBP and a 2.64 mm Hg (p < 0.056) difference in DBP means between the low and
      high alcohol consumption. Corresponding differences at age 43 were SBP 5.28 mm Hg
      (p < 0.023) and DBP 5.4 mm Hg (p < 0.000). Men born in Sweden had a higher
      baseline SBP (delta = 4 mm Hg, CI: 2.11; 6.35) and showed a higher 6 year
      increase in SBP (2.80 mm Hg CI: 0.07; 5.53) than men born abroad. CONCLUSIONS:
      Body composition, ethnicity and alcohol consumption are strong determinants for
      the development of BP. These findings have to be considered in strategies for
      primary prevention of hypertension in younger middle-aged men.

PMID- 14598927
TI  - Recurrent pain in children, socio-economic factors and accumulation in families.
AB  - The aim of this study was to estimate the prevalence of parent-reported pain
      among children in the Nordic countries in 1996, and to describe the association
      between recurrent pain in children and parental socio-economic factors. We also
      wanted to estimate the association between parental pain and childhood pain and
      co-occurrence of different pain patterns in the same child. Data were obtained
      from a cross-sectional survey on children's health and well-being in the Nordic
      countries in 1996. About 10,000 children aged 2-17 years of age were selected
      from population registries. Mean response rate was 68%. We selected the cases >
      or = 7 years where the respondent was the child's biological mother or father,
      yielding a total of 6230 subjects. The adjusted analyses were performed using
      logistic regression in SPSS. The total prevalence of headache, abdominal pain and
      back pain among children 7-17 years of age was 14.9, 8.3 and 4.7%, respectively.
      The most common pain combination was headache and abdominal pain. Pain was most
      frequent among girls. The prevalence was slightly higher in low educated or low
      income families compared to those of high status. Children living in low
      educated, low-income, worker families had approximately a 1.4-fold odds of having
      pain. There was a strong association between the different pain conditions, and
      between pain and other forms of distress in the same child. A site-specific
      association between parental and child pain was also shown, but we assume that
      this might have been mediated through subjective (information) bias.

PMID- 14598928
TI  - Epidemiology of school accidents during a six school-year period in one region in
      Poland.
AB  - BACKGROUND: The aim of the study was to analyse the incidence of school accidents
      in relation to school size, urban/rural environment and conditions of physical
      education classes. METHODS: 202 primary schools with nearly 50,000 students aged
      7-15 years were studied during a 6-year period in the Wloclawek region in Poland.
      RESULTS: There were in total 3274 school accidents per 293,000 student-years.
      Accidents during breaks (36.6%) and physical education (33.2%) were most common.
      Most frequently accidents took place at schoolyard (29.7%), gymnasium (20.2%),
      and in the corridor and stairs (25.2%). After adjustment for students' age and
      sex, student-staff ratio and duration of school hours, urban environment
      increased the probability of accident (OR: 1.25; 95% CI: 1.14-1.38). Middle-size
      schools (8-23 classes) had similar accident rate as small schools (OR: 0.93; 95%
      CI: 0.83-1.04), while schools with 24-32 classes (OR: 1.26; 95% CI: 1.10-1.43)
      and with > or = 33 classes (OR: 1.36; 95% CI: 1.17-1.58) had increased accident
      rate. Presence of a gymnasium was also associated with increased probability of
      accident (OR: 1.49; 95% CI: 1.38-1.61). CONCLUSIONS: Urban environment, larger
      school-size and equipment with full-size gymnasium are important and independent
      risk factors for school accidents. These findings provide some new insights into
      the epidemiology of school-related accidents and may be useful information for
      the planning of strategies to reduce accident incidence in schools.

PMID- 14598930
TI  - Systemic lupus erythematosus in Portugal: diagnosis and disease awareness from
      1970 to 2001.
AB  - A survey of systemic lupus erythematosus patients was carried out in Portugal.
      The length of time from disease appearance to diagnosis remained unchanged over
      the 1970-2001 study period, while awareness of the disease increased considerably
      in the population in the mid-1990s, apparently as a result of an awareness
      campaign conducted by the national lupus support group. The data are compared to
      results from similar studies worldwide.

PMID- 14598929
TI  - Carpal tunnel syndrome. A new feature in the natural history of TOS?
AB  - OBJECTIVE: To ascertain whether carpal tunnel syndrome (CTS) in patients affected
      with toxic oil syndrome (TOS) is associated with conditions and diseases
      considered risk factors for CTS in the general population and/or with certain
      clinical manifestations of TOS. METHODS: We conducted a case-control study to
      compare 89 TOS patients residing in Madrid diagnosed with CTS from 1981 through
      July 2001 (cases) against 638 TOS patients not affected with CTS (controls). Risk
      factors for CTS and clinical manifestations of TOS were analyzed. RESULTS:
      Multivariate logistic regression analysis yielded the following odds ratios (95%
      confidence interval): 3.32 (1.47-7.50) for TOS-related neuropathy; 2.85 (1.14
      7.13) for TOS-related thromboembolic events; 2.63 (1.36-5.06) for female gender;
      0.43 (0.24-0.80) for TOS-related scleroderma; 0.26 (0.12 0.59) for smoking; and,
      in women, 2.53 (1.06-5.70) for fibrositis and 1.84 (1.04-3.20) for miscarriages.
      CONCLUSION: Our study findings support the hypothesis that CTS in TOS patients is
      more linked to certain clinical manifestations of TOS, mainly neuropathy, than to
      conditions and diseases considered risk factors for CTS in the general
      population.

PMID- 14598931
TI  - Incidence of Listeria monocytogenes in food and environmental samples in Italy
      between 1990 and 1999: serotype distribution in food, environmental and clinical
      samples.
AB  - We report the findings of the study of 4185 food samples and 958 environmental
      samples collected in Italy in the period 1990-1999 and tested for the presence of
      Listeria monocytogenes. The strains isolated were biochemically and serologically
      characterised. We found a fairly high percentage of L. monocytogenes
      contamination in food (12.8%), whereas the level of contamination was lower in
      the environment (environment and work surfaces in food processing plants) (6.1%).
      Serotyping showed a prevalence of a few serotypes (i.e., 1/2a, 1/2b, 1/2c and
      4b), which were the same as those found in clinical samples collected during
      outbreaks and from sporadic cases of listeriosis reported in Italy in the period
      considered. The geographical distribution of the strains of L. monocytogenes
      isolated from food samples is very similar to that of the clinical strains.

PMID- 14598932
TI  - Epidemiologic evaluation of the immunity against hepatitis B in Alexandria,
      Egypt.
AB  - BACKGROUND: Hepatitis B (HB) vaccine represents one of the major achievements in
      the 20th century. The most important epidemiologic factor affecting the chronic
      carrier rate is age of infection. The earlier in life an infection occurs, the
      higher the probability that this infection will result in chronic carriage.
      METHODS: A seroepidemiologic study was conducted to examine the impact of HB
      vaccination on the carrier state among a vaccinated group of children (1000)
      compared to a non-vaccinated group (500) aged 6 years in Alexandria, Egypt.
      RESULTS: The rate of HbsAg positivity among the vaccinated group was found to be
      0.8% compared to 2.2% among the non-vaccinated group. The study showed that the
      efficacy of HB vaccine in preventing the carriage of HbsAg, 5 years after full
      course vaccination, was estimated to be around 67%. However, long-term monitoring
      should continue to confirm the efficacy of the vaccine in preventing chronic
      carrier state. On the other hand, studying the exposure to some risk factors
      associated with hepatitis B virus (HBV) infection revealed more or less a similar
      pattern of exposure among both vaccinated and unvaccinated children. CONCLUSION:
      It can be concluded that the significantly lower rate of HbsAg positivity among
      the vaccinated compared to the rate among the non-vaccinated is attributed to the
      preventive effect of the vaccine.

PMID- 14598933
TI  - Is pertussis being considered as a cause of persistent cough among adults?
AB  - A study was conducted to determine the 1124 French Sentinel network general
      practitioners ability to consider pertussis as a cause of persistent cough among
      adults. Pertussis was rarely considered in the differential diagnosis of cough
      (6%). Factors associated with pertussis being considered included younger age,
      shorter cough duration, world health organization clinical definition for
      pertussis, and muscular chest pain.

PMID- 14598934
TI  - Device-related infections in critically ill patients. Part I: Prevention of
      catheter-related bloodstream infections.
AB  - Device utilization in critically ill patients is responsible for a high risk of
      complications such as catheter-related bloodstream infections (CRBSI), ventilator
      associated pneumonia (VAP) and urinary tract infections (UTI). In this article we
      will review the current status of data regarding CRBSI prevention. General
      recommendations include staff education and use of a surveillance program with a
      restrictive antibiotic policy. Adequate time must be allowed for hand washing and
      barrier precautions must always be used during device manipulation. The routine
      changing of central catheters is not necessary and increases costs; it is
      necessary to decrease the handling of administration sets, to use a more careful
      insertion technique and less frequent set replacement. Antiseptic-coated
      catheters appear to reduce catheter colonization but their ability to prevent
      catheter-related infections requires further demonstration. More clinical trials
      are needed to verify the efficacy of measures to prevent CRBSI.

PMID- 14598935
TI  - Natural antibiotic susceptibility of Ewingella americana strains.
AB  - The natural susceptibility of 20 Ewingella americana strains to 72 antibiotics
      was examined. MIC values were determined using a microdilution procedure in
      cation-adjusted Mueller-Hinton broth. Evaluation of natural antibiotic
      susceptibility was performed applying the German standard (where applicable).
      Beta-lactamases were examined with a conventional nitrocefin colony testing
      procedure, activity and induction assays, and SDS-PAGE. Ewingella strains were
      naturally resistant or of intermediate susceptibility to cefaclor, loracarbef,
      cefazoline, cefuroxime, cefoxitin, benzylpenicillin, oxacillin, fosfomycin,
      erythromycin, roxithromycin, clarithromycin, lincosamides, dalfopristin
      quinupristin, ketolides, linezolid, glycopeptides, fusidic acid and rifampicin.
      Uniform natural sensitivity was found with acylureidopenicillins except for
      azlocillin, ticarcillin, several cephalosporins, carbapenems, aztreonam,
      tetracyclines, aminoglycosides, quinolones, azithromycin, folate-pathway
      inhibitors and chloramphenicol. Strains of E. americana were naturally sensitive
      or of intermediate susceptibility to aminopenicillins (with and without beta
      lactamase inhibitors), azlocillin and nitrofurantoin. All ewingellae yielded beta
      lactamases; testing of representative strains revealed that these enzymes belong
      to Ambler class C. Inducibility of beta-lactamase was shown for E. americana ATCC
      33852T, CCUG 35675 and CCUG 42782. The present study describes a database
      concerning the natural susceptibility of E. americana strains to a range of
      antibiotics, which can be applied to validate forthcoming antibiotic
      susceptibility tests of these bacteria. It enlarges the number of
      Enterobacteriaceae expressing naturally-occurring AmpC beta-lactamases.

PMID- 14598936
TI  - Inhibition of nitrofurantoin reduction by menthol leads to enhanced antimicrobial
      activity.
AB  - Nitrofurantoin is a nitroaromatic compound used for the treatment of urinary
      tract infections. Nitrofurantoin activity is regulated by a nitroreduction
      process. It is first reduced by bacterial nitroreductases to active short-life
      intermediates, which are further converted to non-toxic molecules, which
      negatively affect its antibacterial activity. In this study we have shown that
      resistant strains of Klebsiella sp. inactivate the bactericidal activity of
      nitrofurantoin. Also we demonstrated a synergistic effect between menthol and
      nitrofurantoin bactericidal activities against nitrofurantoin susceptible
      Enterobacteriaceae.

PMID- 14598937
TI  - Effect of propolis on virulence factors of Candida albicans.
AB  - Propolis is a resinous substance collected by honeybees from plant sources. Its
      antimicrobial activity has been well documented but little is specifically known
      about its activity on virulence factors of Candida albicans. The aim of this work
      was therefore to evaluate in vitro the propolis effect on yeast-mycelial
      conversion (Y-M), extracellular phospholipase activity and fungal adhesion to
      epithelial cells. The two propolis samples used significantly inhibited the C.
      albicans strains tested, showing a rapid (between 30 seconds and 15 minutes),
      dose-dependent cytocidal activity and an inhibitory effect on Y-M conversion at a
      concentration of 0.22 mg/ml. Moreover, the hyphal length was reduced even at
      lower propolis concentration. Propolis also caused a dose- and time-dependent
      inhibition of phospholipase activity. No clear effect was shown on adherence to
      buccal epithelial cells and surface structure hydrophobicity, but damage to the
      plasma membrane structure was demonstrated with the Propidium Iodide test.

PMID- 14598938
TI  - Clinical characteristics and response to newer quinolones in Legionella
      pneumonia: a report of 28 cases.
AB  - Twenty-eight (11.6%) out of 241 Spanish patients enrolled in an international
      phase III clinical trial of mild to moderate community-acquired pneumonia (CAP)
      comparing gemifloxacin vs. trovafloxacin were diagnosed of Legionnaires' disease.
      A definite diagnosis was established by seroconversion in 13 patients of whom
      only 2 had a positive Legionella urinary antigen. The remaining 15 patients were
      possible Legionella infections based on a single elevated IgG titer (> or =
      1:512). All patients had a radiologically confirmed diagnosis of pneumonia, 5
      (19%) patients were older than 65, comorbidity was present in 9 (33%), and 10
      (36%) had to be hospitalized. Fifteen patients were treated with oral
      gemifloxacin (320 mg/day) and 13 with oral trovafloxacin (200 mg/day). Overall,
      clinical success occurred in 25 (89.3%) patients after 7 days of treatment and
      only 1 patient needed a 14-day treatment. There were only one adverse event
      withdrawal and one clinical failure, and no patients died. In light of the
      favorable clinical outcome, the use of newer fluoroquinolones seems adequate for
      the treatment of suspected or proven Legionella pneumonia.

PMID- 14598939
TI  - Comparison of five antimicrobial regimens for the treatment of brucellar
      spondylitis: a prospective, randomized study.
AB  - Brucellosis, a zoonosis with worldwide distribution, is a systemic infection and
      still an important public health problem in Turkey. The best antimicrobial
      combination and schedule for the treatment of brucellosis with spondylitis has
      not yet been clearly determined. In a prospective and randomized study, we
      compared the efficacy of five antimicrobial regimens for treatment of 102
      patients with lumbar brucellar spondylitis. Patients were randomly assigned to
      receive antimicrobial combination therapy. Twenty patients received streptomycin
      1 g/day intramuscularly for 15 days and tetracycline-HCl, 500 mg every 6 h orally
      for 45 days (ST), 21 patients received streptomycin 1 g/day i.m. for 15 days and
      doxycycline 100 mg every 12 h orally for 45 days (SD), 20 patients received
      doxycycline 100 mg every 12 h orally for 45 days and rifampicin 15 mg/kg per day
      in a single morning dose orally for 45 days (DR), 19 patients received ofloxacin,
      200 mg every 12 h orally for 45 days and rifampicin 15 mg/kg per day in a single
      morning dose orally for 45 days (OR), and 22 patients received streptomycin 1
      g/day i.m. for 15 days and doxycycline 100 mg every 12 h orally for 45 days plus
      rifampicin 15 mg/kg per day in a single morning dose orally for 45 days (SDR).
      Initial therapeutic failure occurred in 2 patients (10%) in the ST regimen group,
      4 patients (19%) in the SD group, 3 patients (15%) in the DR group and 5 patients
      (26%) in the OR regimen. In addition, 2 patients (10%) in the DR group and 5
      patients (26%) in the OR regimen relapsed during the follow-up period. There was
      no relapse in any patients in the ST, SD, and SDR groups. The response rates were
      90% in the ST and 81% in the SD groups. In contrast, there was a maximum good
      response (100%) and no relapse in the SDR group. In conclusion, a combination of
      doxycycline, streptomycin, and rifampicin can be recommended as therapy for
      brucellar spondylitis and to reduce relapse rates.

PMID- 14598941
TI  - Potentiation of antiproliferative drug activity by lonidamine in hepatocellular
      carcinoma cells.
AB  - The ability of lonidamine (LND), a derivative of indazole-carboxylic acid, to
      modulate the cytotoxic activity of anticancer drugs was investigated in two human
      hepatocarcinoma (HCC) cell lines. The cytotoxicity of drugs used singly, in
      association or in sequence was evaluated using the Sulforhodamine B (SRB) assay.
      LND did not appreciably potentiate the effect of antitumor drugs when given
      before or simultaneously, in either cell line. Conversely, a synergistic
      interaction was observed in both cell lines when LND was given after conventional
      drugs. LND produced a moderate decrease in S-phase cell fraction and did not
      induce apoptosis. Conversely, paclitaxel (TAX) induced an important block in G2
      and an increase in apoptosis. Following a 48-h TAX wash out, a progressive
      passage of cells from G2 to M phase was observed with a corresponding increase in
      apoptotic cells. Post-treatment with LND increased the cytotoxicity of some
      antitumor drugs, especially TAX, in hepatocarcinoma cells, possibly by
      preventing, as an energolytic drug, cell damage repair or by producing an
      additional effect on microtubule stabilization.

PMID- 14598940
TI  - Taxanes synergize with the bispecific antibody MDXH447 to enhance antibody
      dependent cell-mediated cytotoxicity.
AB  - The interaction between antibody based therapy and cytotoxic chemotherapy is
      complex. To explore these interactions we investigated, in vitro, the effects of
      IC20 growth inhibitory concentrations of taxanes on bispecific antibody-mediated
      tumor cell cytotoxicity. MDXH447 is a bispecific antibody with specificity for
      the high affinity IgG receptor (CD64) and the type I epidermal growth factor
      receptor type (EGF-R). A431 cells, an epidermoid carcinoma cell line that over
      expresses EGF-R, were exposed to a range of IC20 growth inhibitory concentrations
      of paclitaxel or docetaxel. Interferon gamma activated monocytes were armed with
      MDXH447 and a standard chromium release antibody-dependent cell-mediated
      cytotoxicity (ADCC) assay was performed. Using the Chou and Talalay median effect
      analysis, we found that MDXH447-mediated ADCC was enhanced when A431 target cells
      were pretreated with paclitaxel or docetaxel. Median effect analysis of these
      interactions supported a synergistic interaction (CI < 1). Pretreatment of A431
      cells with taxanes did not increase EGF-R expression compared to untreated
      controls. A431 epidermoid carcinoma cells pretreated with IC20 growth inhibitory
      concentrations of taxanes enhanced interferon gamma activated monocyte mediated
      ADCC killing through MDXH447.

PMID- 14598942
TI  - Doxorubicin, paclitaxel and gemcitabine: a Phase I study of a new sequential
      treatment in stage III B - IV breast cancer.
AB  - Based on the synergistic interactions of the sequence doxorubicin-paclitaxel
      gemcitabine obtained in our preclinical study, a Phase I trial was conducted to
      evaluate the feasibility of this new sequence in breast cancer. Patients with
      stage IIIB-IV breast cancer received doxorubicin on day 1, paclitaxel on day 2
      and gemcitabine on day 6 and 13 (steps IIa, III and V) in cohorts of 3 patients.
      From March 1999 to December 2000, 9 patients were treated. The most important
      toxicity was hematological. The maximum tolerated dose was reached at the second
      level because dose-limiting toxicity occurred in 3 patients. Non hematological
      toxicities were alopecia, diarrhea, asthenia, nausea, mucositis, paresthesia and
      myalgia. A Phase II trial is ongoing to further investigate the activity of this
      new sequential treatment with doxorubicin (50 mg/m2 day 1), paclitaxel (160 mg/m2
      day 2) and gemcitabine (800 mg/m2 day 6) in advanced breast cancer.

PMID- 14598944
TI  - Irinotecan as salvage chemotherapy for advanced small bowel adenocarcinoma: a
      series of three patients.
AB  - Small bowel adenocarcinoma (SBA) is a relatively rare disease. Because of its
      rarity the role of chemotherapy either as adjuvant or for advanced disease has
      not been clearly defined. Therefore any information, including case reports, is
      warranted. We report on three patients with adenocarcinoma of the jejunum and
      ileum. Two patients with positive lymph nodes received postoperative adjuvant
      chemotherapy with 5-fluorouracil-folinic acid (5FU-FA) for 12 months but they
      developed metastatic disease 3 and 8 months later, respectively. The third
      patient was initially treated with the same agents but for metastatic disease.
      All patients were subsequently treated for tumor recurrence with irinotecan 350
      mg/m2 i.v. every 3 weeks as salvage chemotherapy supported by Granulocyte Colony
      Stimulating Factor (GCSF) for 5 days. Two patients achieved a minor response and
      had a dramatic improvement of their symptoms. Their survival times after
      irinotecan administration were 14 and 6 months with an overall survival after
      primary diagnosis of 29 and 27 months, respectively. The third patient who had a
      tumor refractory to 5FU-FA progressed also on irinotecan and had an 8-month
      overall survival. Although conclusions cannot be drawn regarding the role of
      adjuvant chemotherapy in SBA, it seems reasonable to extrapolate from large bowel
      carcinoma experience. Irinotecan seems to have some degree of activity in the
      treatment of SBA but further studies are warranted.

PMID- 14598943
TI  - Postoperative chemotherapy with cisplatin and 5-fluorouracil in cancer of the
      oral cavity and the oropharynx--long-term results.
AB  - Adjuvant chemotherapy has not yet been proven to have a survival benefit for
      patients with head and neck cancer. Studies dealing with this topic have had
      several faults like mingling tumor localizations and treatment modalities. To re
      examine the role of postoperative chemotherapy in oral cavity cancer, a single
      center study was conducted with the attempt to have higher homogeneity. 122
      patients with primary squamous cell carcinoma of the lip, the oral cavity and the
      oropharynx have been treated with 100 mg/m2 cisplatin bolus infusion and 120-h
      continuous infusion of 1000 mg/m2 5-fluorouracil following radical surgery; 99
      patients completed all 3 cycles. The disease-free and overall survival are
      reported and compared to a control group of 161 patients with cancer of the lip,
      the oral cavity and oropharynx treated only with surgery, and a treatment
      dependent prognostic index. After a median follow-up of 79 months (range 5-18
      years), the current 5-year overall survival of the chemotherapy group was 67% and
      the 5-year disease-free survival was 57% while the respective data for the
      control group are 46% and 40%. This difference is statistically significant. The
      comparison with the prognostic index confirmed this result. The chemotherapy
      group suffered from fewer local and more neck relapses and had a much longer
      relapse latency (29 months versus 8 months). The toxicity of the chemotherapy
      regimen was tolerable. In a homogeneous population with resectable oral cavity
      and oropharyngeal cancer, postoperative adjuvant chemotherapy with cisplatin and
      5-fluorouracil resulted in a high overall survival rate which was significantly
      better than in a comparable population treated only with surgery and better than
      the survival expectation calculated with the help of a prognostic index. A
      prospective randomized study of postoperative chemotherapy versus control,
      exclusively in patients with oral cancer, is warranted.

PMID- 14598945
TI  - Toxic epidermal necrolysis associated with gemcitabine therapy in a patient with
      metastatic transitional cell carcinoma of the bladder.
AB  - The authors report on a case of treatment-related toxic epidermal necrolysis in
      an elderly man receiving chemotherapy (gemcitabine) for transitional cell
      carcinoma of bladder and discuss the implications of the case.

PMID- 14598946
TI  - Differences in co-resistance to ciprofloxacin and penicillin depending upon the
      phenotype of erythromycin resistance in Streptococcus pneumoniae.

PMID- 14598947
TI  - Determination of antifungal susceptibilities of Candida species blood culture
      isolates by using the macrodilution method and E-test.

PMID- 14598948
TI  - The effect of profiling dialysate sodium and ultrafiltration on patient comfort
      and cardiovascular stability during haemodialysis.
AB  - The aim of this study was to investigate what affect profiling dialysate sodium
      and ultrafiltration rate had on cardiovascular stability during haemodialysis,
      and if there was any effect on patients' fluid balance, thirst, serum sodium
      levels, blood pressure, or comfort and tolerance. The past decade has seen major
      advances in haemodialysis machine technology. Parallel developments have included
      profiling dialysate sodium levels and fluid removal during dialysis. However,
      some dialysis centres do not use profiling due to fears of long-term detrimental
      effects, especially with regard to hypertension and fluid control. Within my own
      workplace, approximately 30% of haemodialysis treatments utilise either sodium or
      ultrafiltration profiling, or a combination of both. Anecdotally, we have seen an
      increase in cardiovascular stability and haemodialysis tolerance. The aim of this
      study was to identify the effects of profiling haemodialysis, to ensure that the
      treatment we offer patients is safe and effective.

PMID- 14598950
TI  - Vascular access quality monitoring.
AB  - Access dysfunction presents a risk for haemodialysis patients and is costly for
      health care providers. Regular vascular access quality (VAQ) monitoring enables
      the detection of adverse access conditions early allowing timely interventions,
      which will presumably be less invasive, more successful and cheaper. This paper
      reviews all currently used assessment parameters: dynamic and static pressures,
      recirculation and blood flow through the access--and analyses pros and cons of
      each of them. Based on this overview it is concluded that access flow monitoring
      should be the method of choice, possibly combined with monitoring of another
      parameter to further enlarge diagnostic possibilities of the monitoring. The VAQ
      monitoring system developed and used currently in the author's dialysis centre is
      briefly described as an example. The issue of access flow related to
      haemodynamics is briefly mentioned. With the introduction of any VAQ monitoring
      system, one has to acknowledge a change in structure of interventions and that
      the demand for surgical procedures decreases with a concurrent increase in
      percutaneous interventions.

PMID- 14598949
TI  - Should dialysis machines be disinfected between patients' shifts?
AB  - The disinfection of dialysis machines is performed after each session in some
      units but only at the end of the day in other ones. In a multicentre study, in 15
      units (five with and ten without disinfection after each session), the incidence
      of sero-conversion for HCV was reduced to zero, after reinforcement of general
      hygiene precautions only, without changing the above-mentioned machine
      disinfection policies. Recently reported episodes of blood contamination of
      dialysis machines beyond pressure transducers demonstrate that pressure isolator
      inspection and care should be added to the general hygiene precautions. In a
      second investigation, no difference was found in dialysate bacterial and
      endotoxin characteristics between dialysis machines, disinfected after each
      dialysis (n = 2) and those disinfected at the end of the day only (n = 2). In
      conclusion, the systematic disinfection of all dialysis machines after each
      session does not appear to help prevent HCV infection nor to have a detectable
      impact on optimal dialysate bacterial and endotoxin characteristics.

PMID- 14598951
TI  - Psychological care of the haemodialysis patient.
AB  - The psychological care of patients at the haemodialysis unit is becoming an
      increasingly important aspect of the overall treatment of patients with end-stage
      renal failure. As more is understood and reported regarding the impact of
      psychological factors on physical processes it becomes crucial that good quality
      psychological care is delivered to patients by nurses working at the
      haemodialysis unit. This study aimed to look at haemodialysis patients'
      perceptions of their treatment to discover if a dialysis centre in Southern
      England might benefit from a more formal system of psychological care. The data
      revealed four main themes that were of particular importance to the participants
      of this study: The New Self, Coping, Medical Concerns and Psychological Care.
      Within these areas of importance, the need for good quality information, the need
      for a suitable dialysis environment and the importance of social and family
      support were evident. Although the psychological care system that was in place at
      the unit appeared to be working well a more formal system of care might improve
      the patient experience.

PMID- 14598952
TI  - Campus and education: an experience with PD patients.
AB  - Every day patients on peritoneal dialysis (PD) must focus on their dialysis
      schedules and on nutritional and therapeutic prescriptions. Unfortunately, over
      time all these actions may not follow the initial protocol. In order to evaluate
      patient's knowledge and approach to dialysis, an alternative educational tool to
      hospital or home was investigated. The campus was utilised as a place for re
      training and detecting and correcting discrepancies in knowledge and the
      management of techniques. A continuous educational programme involves some re
      training of PD patients and this approach helps us to identify whether the
      treatment management at home is in accordance with the information given at the
      start of the dialysis, but there was a need to improve on this and to improve
      patient understanding and compliance. The campus was chosen as an alternative
      educational process with the aim of involving the patients themselves and their
      families to achieve additional benefits and long-term success of the therapy.
      This initiative, outside the hospital and in collaboration with professional
      figures not affiliated with the dialysis unit, hoped to offer patients new
      knowledge about: dialysis technique and procedures, prevention of infectious
      complications, nutrition and physical activity.

PMID- 14598953
TI  - Human rights: implications for patients and staff.
AB  - Originating from wider declarations of fundamental human rights, individual human
      rights in the field of health care, also called patients' rights, have been
      elaborated, developed and implemented by most international organisations,
      including the European Union and the World Health Organisation. The Council of
      Europe is however, particularly prominent in its work in the field of human
      rights, having drawn up a number of vital international treaties, among them and
      most importantly the Convention on Human Rights and Biomedicine, which
      strengthens internationally the legal position of the patient and the research
      subject in setting a minimum level of protection in respect of individual human
      rights and health and is binding upon the member states that have ratified it.
      Nonetheless, it needs to be examined to see if the European Union would be a
      better alternative to regulate these patients' rights.

PMID- 14598954
TI  - Encouraging self-administration of erythropoietin.
AB  - European Best Practice Guidelines of 1999 for managing anaemia in patients with
      kidney failure state that patients using the subcutaneous route should be
      encouraged to self-administer epoetin whenever possible. This article argues for
      and substantiates the need to develop an education programme, which should
      consist of group and one-to-one teaching sessions with discussion, role-play,
      visual aids and demonstration. Information booklets will be provided covering
      blood pressure monitoring, ordering and storage of medication and safe disposal
      of syringes. Methods to evaluate the education programme include direct
      observation, laboratory reports, patient care plans and feedback. The theoretical
      benefits of such a programme should include; improved cardiovascular function
      with a more compliant patient enjoying an improved quality of life. The
      organisation should benefit through lower costs and a structured method of audit.

PMID- 14598955
TI  - The mysterious standard deviation.

PMID- 14598956
TI  - Puncture of the arteriovenous fistula: bevel upward or bevel downward?

PMID- 14598957
TI  - Job promotion: our own responsiblity.

PMID- 14598958
TI  - Case finding in children in contact with adults in the house with TB.

PMID- 14598959
TI  - The transmission of tuberculosis in confined spaces: an analytical review of
      alternative epidemiological models.
AB  - Tuberculosis (TB) is a disease that is closely associated with poverty, with
      transmission occurring in situations where infected persons are in close contact
      with others in confined spaces. While it is well recognised that overcrowding
      increases the risk of transmission, this increased risk has not been quantified
      and the relationship between overcrowding and duration of exposure is not well
      understood. This paper analyses three epidemiological models that have been used
      to predict the transmission of airborne disease in confined spaces: the Mass
      Action model, Riley, Murphy and Riley's model and Gammaitoni and Nucci's model. A
      study is presented to demonstrate the range of applicability of each model and
      show how they can be applied to the transmission of both TB and diseases with
      short incubation periods such as measles. Gammiatoni and Nucci's generalised
      formulation is shown to be the most suitable for modelling airborne transmission
      in ventilated spaces, and it is subsequently used in a parametric study to
      evaluate the effect of physical and environmental factors on the rate of disease
      transmission. The paper also presents reported quanta production data for several
      TB outbreaks and demonstrates that the greatest risk of TB infection is during
      clinical procedures that produce large quantities of aerosol, such as
      bronchoscopy or intubation.

PMID- 14598960
TI  - The potential of human neutrophil peptides in tuberculosis therapy.
AB  - The problems of drug resistance and bacterial persistence in tuberculosis have
      prompted scientists to search for clues from the latest advances in microbiology
      and immunology. Recent research on human neutrophil peptides (HNPs) has
      highlighted their bactericidal action against Mycobacterium tuberculosis and
      suggested that neutrophils may play a more important defensive role in
      tuberculosis than previously thought. Human neutrophil peptides belong to a
      family of antimicrobial and cytotoxic peptides known as 'defensins'. Neutrophils
      use both oxidative and non-oxidative microbicidal mechanisms to provide the host
      with innate immunity against microbial infections. Defensins are most abundant
      among an array of oxygen-independent antimicrobial proteins and peptides in
      neutrophil granules. Defensins are effective against a wide spectrum of microbes
      including bacteria, viruses, fungi, spirochetes and mycobacteria. In addition to
      direct antimicrobial activity, HNPs can potentially influence the inflammatory or
      immune responses by modulating cytokine production or acting like opsonins or
      chemotactic factors. HNPs are active against M. tuberculosis grown in vitro or
      within macrophages. HNPs released by neutrophils recruited in the early lesion
      could attract monocytes to the site and macrophages may in vivo uptake the
      extracellular HNPs and kill the intracellular pathogens. As such, HNPs are
      potential therapeutic agents against tuberculosis. HNPs are also cytotoxic
      against a wide range of normal mammalian cells; however, there is evidence that
      defensins may not cause significant cytotoxicity at the therapeutic level.
      Finally, the clinical application of HNPs must be evaluated in the context of
      possible drug resistance, as some resistance-associated genes have been
      identified.

PMID- 14598961
TI  - Passive versus active tuberculosis case finding and isoniazid preventive therapy
      among household contacts in a rural district of Malawi.
AB  - SETTING: Thyolo district, rural Malawi. OBJECTIVES: To compare passive with
      active case finding among household contacts of smear-positive pulmonary
      tuberculosis (TB) patients for 1) TB case detection and 2) the proportion of
      child contacts aged under 6 years who are placed on isoniazid (INH) preventive
      therapy. DESIGN: Cross-sectional study. METHODS: Passive and active case finding
      was conducted among household contacts, and the uptake of INH preventive therapy
      in children was assessed. RESULTS: There were 189 index TB cases and 985
      household contacts. Human immunodeficiency virus (HIV) prevalence among index
      cases was 69%. Prevalence of TB by passive case finding among 524 household
      contacts was 0.19% (191/100000), which was significantly lower than with active
      finding among 461 contacts (1.74%, 1735/100000, P = 0.01). Of 126 children in the
      passive cohort, 22 (17%) received INH, while in the active cohort 25 (22%) of 113
      children received the drug. Transport costs associated with chest X-ray (CXR)
      screening were the major reason for low INH uptake. CONCLUSIONS: Where the
      majority of TB patients are HIV-positive, active case finding among household
      contacts yields nine times more TB cases and is an opportunity for reducing TB
      morbidity and mortality. The need for a CXR is an obstacle to the uptake of INH
      prophylaxis.

PMID- 14598962
TI  - Management and outcome of tuberculosis patients who fail treatment under routine
      programme conditions in Malawi.
AB  - SETTING: All 43 non-private hospitals (three central, 22 district and 18 mission)
      in Malawi that registered and treated TB cases between 1 July 1999 and 30 June
      2000. OBJECTIVES: To determine 1) the number of new smear-positive PTB patients
      who failed treatment, 2) the management of patients who failed, 3) their
      treatment outcome and 4) culture and drug sensitivity results. DESIGN:
      Retrospective data collection using TB registers and laboratory culture and drug
      sensitivity registers. RESULTS: Ninety patients failed treatment, 60 (67%) at 5
      months and 30 (33%) at the end of treatment. Sixty-four (71%) failure patients
      were registered and commenced on anti-tuberculosis treatment. Of these, 95% were
      registered in the same hospital as before, 89% were given a different TB
      registration number, 67% were correctly registered as 'failures' and 61% were
      treated within one month of failing the previous regimen. Forty-eight (75%) re
      treated patients were cured. Only 31 (34%) of the 90 patients had sputum sent for
      culture and drug sensitivity testing. In 11 patients with cultures of M.
      tuberculosis, eight were fully sensitive and three had mono-resistance to
      isoniazid. CONCLUSION: While the outcome of failure patients who start
      retreatment is good, there are several programmatic deficiencies that need to be
      corrected.

PMID- 14598963
TI  - Encouraging outcomes in the first year of a TB control demonstration program:
      Orel Oblast, Russia.
AB  - SETTING: Orel, Russia. OBJECTIVE: To evaluate outcomes of tuberculosis (TB)
      patients treated in the first year of a TB control demonstration project using a
      revised strategy of directly observed treatment, short-course (DOTS). Standard
      methods recommended by World Health Organization (WHO) were adapted to include
      mycobacterial cultures. DESIGN: Retrospective cohort analysis of TB patients
      diagnosed between October 1999 and September 2000. RESULTS: Among 749 TB
      patients, 65% had bacteriologic confirmation of pulmonary TB, 31% were diagnosed
      clinically, and 4% had extra-pulmonary TB. Most (92%) had no previous TB
      treatment, but 8% were identified as retreatment cases. Of all patients, 41% had
      new sputum smear-positive TB. No patients were HIV-infected. Multidrug-resistant
      (MDR) TB levels were 3% among new and 17% among retreatment patients. Among new
      smear-positive patients, treatment success was 79% (72% cure, 7% completion);
      remaining outcomes were 8% failure, 3% default, 8% death, and 1% transfer.
      Success rates for new culture-positive and clinically diagnosed patients were 81%
      and 91%, respectively. CONCLUSION: Despite historical differences, successful
      implementation of the revised TB strategy in Russia is possible. Treatment
      success rates were high, suggesting WHO targets of 85% cure for smear-positive
      patients is attainable. Obstacles include drug resistance and elevated death
      rates among smear-positive patients.

PMID- 14598965
TI  - Microscopic examination and treatment outcomes of new pulmonary tuberculosis
      cases in Istanbul dispensaries between 1998 and 2000.
AB  - SETTING: Twenty-four public tuberculosis dispensaries in Istanbul. OBJECTIVE: To
      investigate microscopic examination of new pulmonary tuberculosis (TB) cases and
      treatment outcomes of smear-positive cases. DESIGN: A retrospective analysis of
      12572 new pulmonary tuberculosis cases between 1998 and 2000. METHODS:
      Microscopic examination of sputum smears of all patients and treatment outcomes
      of smear-positive cases were evaluated. RESULTS: Of 12572 new TB cases registered
      between 1998 and 2000, 78.1% (n = 9822) were pulmonary and 21.9% (n = 2750) were
      extra-pulmonary TB cases. Of 9822 new pulmonary TB cases, 5438 (55.4%) were
      sputum smear-positive and 2154 (21.9%) had no sputum examination. In smear
      positive pulmonary cases, treatment outcomes were classified as follows: 2521
      (46.4%) cured, 1926 (35.4%) treatment completed, 128 (2.4%) treatment failure,
      514 (9.4%) default, 260 (4.8%) transfer out and 72 (1.3%) died. Treatment success
      was 81.8% (n = 4447). Between 1998 and 2000, the smear-positive case rate
      improved from 47.5% to 61.5% and the cure rate improved from 41.8% to 51.1%.
      CONCLUSION: The microscopic diagnosis and cure rates are low in Istanbul
      dispensaries. The laboratories should be re-organised and directly observed
      treatment should be performed.

PMID- 14598964
TI  - Tuberculosis: do we know enough? A study of patients and their families in an out
      patient hospital setting in Karachi, Pakistan.
AB  - SETTING: In Pakistan approximately 5.7 million people suffer from tuberculosis,
      with 260 000 new cases occurring every year. This study was conducted in an
      outpatient hospital setting in Karachi. OBJECTIVE: To explore the level of
      awareness about tuberculosis amongst patients and their families, and recommend
      strategies for increasing understanding of the disease. DESIGN: Descriptive cross
      sectional survey based on a structured questionnaire using convenience sampling.
      RESULTS: Of the 203 patients interviewed, 131 were males. Nearly 82% knew that
      tuberculosis is contagious and 78% were aware that lungs are commonly affected.
      Almost half knew that it spreads by droplets and causes cough and that treatment
      is long and costly. With regard to commonly affected age and sex, however,
      respectively only 43% and 23% had the correct knowledge. Less than one third
      could identify appropriate risk factors and ways to cure and limit spread. Almost
      half considered tuberculosis to be a social stigma. Media emerged as the main
      source of information. Respondents with more than 12 years of formal education
      were more likely to have better knowledge. CONCLUSIONS: Further population-based
      studies are recommended. Misconceptions about tuberculosis need to be removed
      through focused health education messages. The importance of complete and
      appropriate treatment needs to be emphasised.

PMID- 14598966
TI  - Trends and patterns of tuberculosis: interpretations and prospects of
      tuberculosis control in Vojvodina, Yugoslavia, 1987-2000.
AB  - AIM: To assess the trends and pattern of tuberculosis in Vojvodina, Yugoslavia.
      METHODS: Using a retrospective design, data on 393 diagnosed TB cases were
      investigated for the years 1987, 1993 and 2000. RESULTS: TB case notification has
      been increasing in Vojvodina. The number of reported TB cases was 146 in 1987,
      101 in 1993 and 146 in 2000; cases were predominantly in the age group 20-39
      years (44.5%) in 1987, compared to the 40-59 year age group in 1993 and 2000
      (38.6% and 45.9%, respectively). The majority of patients belonged to lower socio
      economic groups. Manifestations of TB such as cough, weight loss and exhaustion
      were common. With the increasing trend of alcoholism from 1987 to 2000, delays in
      reporting were noticed. TB-related mortality was 1.4% in 1987 and 4.1% in 2000.
      Resistance to TB drugs among previously treated cases was 2.7% in 1987, 0.9% in
      1993 and 2.7% in 2000. With respect to the increasing resistance, the levels of
      detection and surveillance were poor. The implementation of the DOTS strategy
      remained fairly low. CONCLUSION: TB is a chronic problem in Vojvodina. Prompt
      community-oriented actions need to be taken to improve case detection and cure
      rates through DOTS.

PMID- 14598967
TI  - Characteristics associated with reported sputum culture conversion in the era of
      re-emergent Mycobacterium tuberculosis in the State of North Carolina, 1993-1998.
AB  - OBJECTIVE: To determine predictors of sputum culture conversion among patients
      undergoing treatment for pulmonary tuberculosis. DESIGN: Cohort study based on
      data collected through the expanded tuberculosis control program in the State of
      North Carolina, USA. Survival analysis using Kaplan-Meier product-limit estimator
      and Cox proportional hazards models was employed to compute estimates for time to
      sputum conversion and rate ratios, respectively. RESULTS: Sputum conversion was
      reported in 1144 of 1735 cases (66%). Documented conversion rose significantly
      from 52.9% at baseline to a peak of 95.1% by the end of the study, representing a
      5.1% annual increase in the proportion of patients with reported conversion (P =
      0.007). Patients co-infected with the human immunodeficiency virus (HIV) had a
      46% lower rate of sputum conversion than non-HIV-infected TB patients (adjusted
      hazard ratio [HR] 0.54, 95%CI 0.44-0.67). Other significant predictors of
      reported conversion rates included directly observed therapy (DOT) (P = 0.02),
      the number of drugs used in the therapy regimen (P = 0.001), and non-injectable
      drug use (P = 0.012). CONCLUSION: The rate of reported sputum culture conversion
      in TB patients was low, consistent with an earlier population-based report. The
      symbiotic relationship between HIV and mycobacterial infection might be a factor
      that compromised response to therapy in coinfected individuals.

PMID- 14598968
TI  - Blinded rechecking of sputum smears for acid-fast bacilli to ensure the quality
      and usefulness of restaining smears to assess false-positive errors.
AB  - SETTING: Microscopy Centres, Velliyur Tuberculosis Unit, Tiruvallur District,
      Tamil Nadu, India. PROCEDURES: Twelve microscopy centre laboratory technicians
      examined 41978 direct sputum smears for acid-fast bacilli. Senior Tuberculosis
      Laboratory Supervisors (STLS) checked all positive smears (4696) and 10% of
      negative smears (4776) in an unblinded fashion as per Revised National
      Tuberculosis Control Programme (RNTCP) guidelines. Ten per cent of the positive
      and negative slides and another 10% of unchecked negative slides were selected
      systematically for blinded rereading at the Tuberculosis Research Centre (TRC);
      422 slides were reread without and with restaining. RESULTS: Unblinded checking
      by STLS of the smears read by the laboratory technicians yielded 95 to 100%
      agreement. Blinded rereading at the TRC revealed that false-negative errors were
      greater among the laboratory technicians (2-7%) than the STLS (0-3%). Restaining
      and blinded rereading of slides reduced false-positive errors from 27% to 7%.
      CONCLUSIONS: Blinded rereading at the reference centre facilitates assessment of
      laboratory technicians and STLS. Restaining before rereading the smears was found
      to be useful for precise estimation of false-positive errors.

PMID- 14598969
TI  - Association of initial tuberculin sensitivity, age and sex with the incidence of
      tuberculosis in south India: a 15-year follow-up.
AB  - OBJECTIVE: To determine the association of initial tuberculin sensitivity, age
      and sex with the development of tuberculosis. METHODS: A 15-year follow-up of
      280000 subjects in south India, where new cases of tuberculosis were detected
      mainly by periodic population surveys. Life-table technique was employed to
      estimate tuberculosis incidence and disease risk in survivors. The independent
      effect of tuberculin sensitivity, sex and age at intake was determined using
      Cox's proportional hazard model. RESULTS: Taking subjects with reaction size 0-7
      mm to 3 IU PPD-S as reference group, the adjusted relative risk (RR) for
      developing culture-positive tuberculosis was 1.1, 1.9, 2.9, 3.6 and 3.3 for those
      with indurations of 8-11, 12-15, 16-19, 20-24 and > or = 25 mm (P < 0.01).
      Considering subjects aged 0-4 years as reference group, the adjusted RR for the
      other groups increased from 1.7 to 10.8 (P < 0.01). Males had a substantially
      higher incidence (adjusted RR 3.0, P < 0.001). The risk of culture-positive
      tuberculosis over 15 years in survivors was 3.3% (5.0% in males and 1.6% in
      females), and increased substantially with tuberculin sensitivity at intake. In
      those with > or = 12 mm at intake, the approximate lifetime risk was 6.1% (8.6%
      in males and 3.1% in females). CONCLUSION: The incidence of tuberculosis
      increased steadily with tuberculin sensitivity to PPD-S and age at intake. Males
      had a significantly higher risk than females in every PPD-S group and the overall
      risk was three-fold higher.

PMID- 14598970
TI  - Qualitative tuberculin response in the diagnosis of tuberculosis in apparently
      healthy schoolchildren.
AB  - SETTING: School-based cross-sectional study. OBJECTIVE: To assess the value of
      qualitative tuberculin responses (turgid and non-turgid type) in diagnosis of
      tuberculosis disease in apparently healthy schoolchildren. DESIGN: Qualitative
      tuberculin responses were assessed in 548 apparently healthy schoolchildren.
      Tuberculin-positive (> or = 10 mm) children were investigated for evidence of
      tuberculosis. The relationship between the types of qualitative tuberculin
      response and occurrence of tuberculosis was studied. RESULTS: Eighty-eight
      (16.1%) children were found to be tuberculin-positive. Of these, 68 had non
      turgid reaction whereas 20 had turgid reaction. Most of the children with a
      reaction of 5-9 mm had a non-turgid type of tuberculin reaction. Only four
      children with non-turgid reaction had tuberculosis, while 18 children with turgid
      reaction had tuberculosis disease (P < 0.0001). A larger tuberculin reaction was
      found to be associated with a higher occurrence of tuberculosis (P = 0.016 by
      linear regression method). CONCLUSION: The observations indicate a possible
      relation between turgid reaction and tuberculosis disease.

PMID- 14598971
TI  - Prevalence of Beijing genotype in Latvian multidrug-resistant Mycobacterium
      tuberculosis isolates.
AB  - SETTING: Predominant genotypes of Mycobacterium tuberculosis include the Beijing
      family, which has caused large tuberculosis outbreaks and has been associated
      with increased virulence and multidrug resistance (MDR). OBJECTIVE: To search for
      the Beijing genotype among Latvian MDR patients to characterise their DNA
      isolates at the molecular level. DESIGN: MDR isolates were spoligotyped and
      tested for gene mutations by automatic nucleotide sequencing. RESULTS: Of 109
      isolates examined, 95 were located in six clusters of 2 to 63 isolates each. The
      63 isolates in the largest cluster had an identical pattern corresponding to the
      Beijing genotype. The remaining isolates were of a non-Beijing genotype and
      formed another large group whose similarity ranged from 72% to 100%. Mutations in
      the rpoB and katG genes were compared in the Beijing and non-Beijing strains. In
      both groups, the rpoB gene mutations predominated in codons S531L (52.2%) and
      D516V (14.7%). Double mutations in the rpoB gene were observed in 8.2% of the
      isolates, most of them located among Beijing-type isolates. The katG gene
      mutation S315T (98.4%) was prevalent among all isolates. CONCLUSION: Molecular
      analysis of MDR isolates of M. tuberculosis demonstrates that the Beijing
      genotype, most likely due to recent transmission, is prevalent in Latvia among
      MDR patients and that this genotype can be associated with double mutations.

PMID- 14598972
TI  - Characterization of clinical isolates of Mycobacterium tuberculosis resistant to
      drugs and detection of RpoB mutation in multidrug-resistant tuberculosis in the
      Philippines.
AB  - SETTING: Retrospective study of Mycobacterium tuberculosis isolates at the
      STD/AIDS Cooperative Central Laboratory, Philippines. OBJECTIVE: To describe
      patterns of M. tuberculosis resistance against first-line anti-tuberculosis
      drugs, and to analyze the rpoB gene codon mutation of rifampicin (RMP) resistant
      isolates and correlate genotypic and phenotypic patterns. DESIGN: One hundred and
      sixty-four M. tuberculosis complex isolates were retrieved for phenotypic
      analysis; 89 were resistant to any anti-tuberculosis drug and 50 were RMP
      resistant, whereas 48 were multidrug-resistant (MDR). Of these 48, only 33 were
      available for genotypic analysis of the rpoB gene. RESULTS: Most drug-resistant
      isolates were phenotypically resistant to isoniazid (INH) (93%), and the
      probability of an RMP-resistant isolate becoming MDR was 96%. In 33 MDR isolates,
      13 types of mutations in nine independent codons were identified; the most
      frequently mutated codons were S531L (61%) and G510H (15%), which were present in
      76% (25/33) of the isolates. S531L was noted in 85.7% of the RMP + INH + SM
      resistant isolates, while only 80% of the isolates with INH + RMP, EMB + SM
      resistance showed this mutation. CONCLUSION: The high probability of RMP isolates
      being MDR suggests that genetic analysis of RMP resistance is useful in detecting
      MDR-TB. Worldwide accumulation of findings on circulating MDR-TB strains provides
      indispensable information about the re-emergence of TB.

PMID- 14598973
TI  - Impaired interleukin-1beta converting enzyme (ICE) activity in patients with
      pulmonary tuberculosis.
AB  - We measured the activity of IL-1beta converting enzyme (ICE) of monocytes from
      pulmonary tuberculosis (PTB) patients. Peripheral blood mononuclear cells (PBMCs)
      and serum were collected from PTB patients (n = 16) and healthy subjects (n = 6).
      Serum IL-18 levels were significantly higher in PTB patients (515.9 +/- 326.5
      pg/ml) than in controls (108.7 +/- 65.2 pg/ml) (P < 0.01), but gradually
      decreased with tuberculosis therapy. ICE activity was significantly lower in TB
      patients (65.3 +/- 34.4 vs. 142.2 +/- 75.6 U/mg) (P < 0.05). Serum IL-18 levels
      inversely correlated with ICE activity (P < 0.05). Altered ICE activity may
      explain why there is reduced IFN-gamma production from PBMCs; however, serum IL
      18 is probably not regulated by ICE in monocytes in TB patients.

PMID- 14598974
TI  - What the Wizard of Oz couldn't give.

PMID- 14598975
TI  - The best NICU in America 2003.

PMID- 14598976
TI  - Finding one's own best NICU in America.

PMID- 14598977
TI  - Early recognition of infant malignancy: the five most common infant cancers.

PMID- 14598979
TI  - An evidence-based guideline for introducing oral feeding to healthy preterm
      infants.
AB  - The ability of a preterm infant to make the transition from gavage to oral nipple
      feeding depends on the infant's neurodevelopment in relation to behavioral
      organization, to a rhythmic suck-swallow-breathe pattern, and to
      cardiorespiratory regulation. Research-based knowledge about infant
      neurodevelopment in these three areas has led to the creation of a semidemand
      feeding method to aid in this transition. The method combines the use of
      nonnutritive sucking to promote awake behavior for feeding, use of behavioral
      assessment to identify readiness for feeding, and systematic observation of and
      response to infant behavior cues to regulate frequency, length, and volume of
      oral feedings. Semidemand feeding may be individualized for healthy preterm
      infants. This article discusses both the relevant knowledge about
      neurodevelopment and the semidemand feeding method itself.

PMID- 14598978
TI  - Calcium and bone health in infants.
AB  - Osteopenia, rickets, and fractures from nutrient deficiencies can occur during
      infancy, particularly in preterm infants. Bone mass accretion during the first
      year of life is equal to or greater than that achieved at any other stage of
      life, including adolescence. Optimizing calcium and bone status during infancy
      can have immediate benefits in maintaining calcium homeostasis and preventing
      disturbances in bone mineralization and can provide long-term benefits by helping
      infants to later reach their maximum genetic potential for peak bone mass, a
      prerequisite for the prevention of osteoporosis and its complications. Dietary
      calcium requirements during infancy generally reflect the need to achieve normal
      growth and bone mineralization because 99 percent of total body calcium is
      present in the skeleton. Knowledge of physiologic factors that determine infant
      calcium requirements and the bioavailability of calcium from various dietary
      sources is important to ensuring bone health during infancy. Also key are the
      practical issues related to optimizing calcium nutriture in infants born at term
      and prematurely.

PMID- 14598981
TI  - Types of research designs.
AB  - An experimental design is necessary for making cause-and-effect judgments about
      study variables. Although most researchers would agree that the experimental
      design is desirable, such a design is not possible or appropriate for every study
      -and even without an experimental design for support of the hypothesis, enough
      evidence might exist for a researcher to feel somewhat comfortable that variable
      X causes Y. At the very least, it can be demonstrated that X is always related to
      Y in some number of settings, with multiple samples of subjects and with controls
      for as many variables as possible. Before deciding to change a practice based on
      research findings, however, the clinician must also determine if X is not related
      to Y in some cases. Without experimental findings, the amount and quality of
      evidence available must be considered. This column has described three major
      types of research: experimental, quasi-experimental, and nonexperimental. Each
      type of research can produce valuable scientific evidence if the study is
      designed and implemented carefully. The type of research design and its
      appropriateness for the specific research question is only one consideration in
      critiquing research findings and making decisions about the application of those
      findings in practice settings. Future columns will address other considerations.

PMID- 14598980
TI  - Correlates of depressive symptoms in mothers of preterm infants.
AB  - PURPOSE: To identify factors related to depressive symptoms in mothers of preterm
      infants and to changes in depressive symptoms between hospitalization and when
      the infant was six months corrected age and to determine whether these factors
      differentiate mothers at high risk for depression from mothers at low risk for
      depression. DESIGN: Correlational. SAMPLE: During hospitalization, 39 mothers of
      preterm infants and, at six months corrected infant age, 34 mothers of preterm
      infants. MAIN OUTCOME VARIABLE: Depressive symptoms as measured on the Center for
      Epidemiological Studies Depression scale. RESULTS: At enrollment, 19 mothers
      (48.7 percent) had elevated depressive symptom scores. When the infants were six
      months corrected age, mean scores had decreased by 36 percent, and only 20
      percent of the mothers had elevated scores. During hospitalization, the
      correlates of depressive symptoms were similar to the factors that differentiated
      between mothers at high risk and those at low risk for depression. However, the
      correlates of depressive symptoms during hospitalization were different from
      correlates of changes in depressive symptoms between hospitalization and six
      months corrected infant age. Identifying correlates of maternal depressive
      symptoms may lead to earlier identification and treatment of women at risk for
      depression, thereby decreasing the negative effects on infant development.

PMID- 14598982
TI  - Nurse managers: the ties that bind.
AB  - The staff nurses' immediate manager directly influences an NICU's ability to
      attract and retain professional nurses. This makes it especially important that
      nurse executives and administrators identify opportunities to better meet the
      needs of their nurse managers and measure the impacts of their decisions. Data
      about front-line manager turnover need to be measured, reported, and examined. No
      longer can organizations afford to view managers as another expense; they are an
      asset on the balance sheet. Strategic planning for the recruitment and retention
      of nurse managers will be vital both to an organization's healthy bottom line and
      to the quality of its patient care.

PMID- 14598983
TI  - Toy or tool of the trade? Part I.

PMID- 14598984
TI  - Matthew.

PMID- 14598985
TI  - Porites ulcerative white spot disease: description, prevalence, and host range of
      a new coral disease affecting Indo-Pacific reefs.
AB  - The results of an investigation of a new coral disease affecting Indo-Pacific
      reefs are presented. Porites ulcerative white spot disease (PUWS) is
      characterized by discrete, bleached, round foci, 3 to 5 mm in diameter, that may
      either regress or progress to full tissue-thickness ulcerations that coalesce,
      occasionally resulting in colony mortality. Monitoring of 25 diseased and 5
      healthy reference colonies for 17 mo revealed that advanced stages of the disease
      were characterized by lesion coalescence, partial colony death (i.e. portions of
      the colony still alive; n = 17) and total colony death (n = 2). Field
      transmission experiments revealed that 95% of healthy colonies developed lesions
      within 5 wk after continual exposure to diseased branches, while 60% of the
      reference colonies remained healthy. The host range of PUWS includes branching
      and massive Porites spp., and prevalence per species was positively correlated
      with species density. On 10 reefs surveyed in the Central Philippines, 22 +/- 7%
      (mean +/- SE) of poritid colonies were infected, and the disease was present on
      80% of the surveyed reefs. Poritids are dominant Indo-Pacific reef builders; a
      disease targeting this genus could cause major shifts in community structure over
      time. This report contributes to the limited knowledge of PUWS impacts in this
      region.

PMID- 14598986
TI  - Bacterial influences on Atlantic halibut Hippoglossus hippoglossus yolk-sac
      larval survival and start-feed response.
AB  - A bacteria-free halibut larval rearing system was used to test 20 bacterial
      isolates, from British halibut hatcheries, for their toxicity towards halibut
      yolk-sac larvae under microbially controlled conditions. The isolates tested
      spanned a range of genera and species (Pseudoalteromonas, Halomonas marina,
      Vibrio salmonicida-like, Photobacterium phosphoreum and V. splendidus species). A
      pathogen of turbot, Scophthalmus maximus, V. anguillarum 91079, and 2 isolates
      from adult halibut were also included. Isolates were inoculated, at a
      concentration of 5 x 10(2) cfu ml(-1), into flasks containing 25 recently hatched
      axenic halibut larvae, using a minimum of 3 flasks for each treatment. Control
      survivals to 38 d post-hatch for the 3 experiments averaged 84, 51.5 and 49%,
      respectively. With the exception of V. anguillarum 91079, which was highly
      pathogenic towards halibut yolk-sac larvae, there was no statistically
      significant difference in survival between the controls and the different
      treatments. This suggests that most of the bacteria routinely isolated from
      halibut hatcheries are not harmful to yolk-sac larvae, even though most flasks
      contained in excess of 5 x 10(6) cfu m(-1) of the inoculated organism when the
      experiments were terminated. Three organisms previously shown to inhibit growth
      of bacteria in vitro were tested for their ability to protect halibut yolk-sac
      larvae against invasion by V. anguillarum. In 4 separate challenge experiments
      none of the test isolates, a Pseudoalteromonas strain and 2 Carnobacterium-like
      organisms, showed any protective effect. To investigate how particular bacteria
      influence their start-feed response, larvae were fed axenic and gnotobiotic
      Artemia colonized with a range of different Vibrio spp., and examined after 8 d.
      There were no statistically significant between-treatment differences in the
      proportion of Artemia-containing larvae, indicating that bacterial contamination
      of the live food does not appear to influence initiation of the feeding response.

PMID- 14598987
TI  - Starvation of Flavobacterium psychrophilum in broth, stream water and distilled
      water.
AB  - Physical changes in Flavobacterium psychrophilum, the causative agent of rainbow
      trout fry syndrome (RTFS), were examined over a 19 wk period of starvation.
      Bacteria were maintained in either Cytophaga broth, filtered stream water, or
      filtered distilled water, or were maintained in broth after disinfection as a
      negative control for dead bacteria. Culturability and viability of the bacterium
      were assessed using colony-forming units (CFUs) and a commercially available
      live/dead kit. Antigenic profiles and general morphology of the bacterium were
      also examined using Western blot analysis and electron microscopy, respectively.
      The bacterium appeared to stop multiplying and became smaller and rounded when
      maintained in stream water. Its culturability declined until it was no longer
      possible to obtain colonies on agar plates at the end of the trial at 19 wk, and
      results from the live/dead kit did not correspond with the viability obtained as
      CFUs in culture. However, it was still possible to obtain growth of the bacterium
      after 36 wk with a resuscitation step in Cytophaga broth. Bacteria maintained in
      distilled water or treated with a disinfectant appeared non-viable using the
      live/dead kit and were unable to grow on agar 1 h after setting up the
      experiment; no morphological changes were observed in the bacteria maintained
      under these conditions. Bacteria maintained in broth were present as long, slim
      rods, some of which developed into 'ring' formations. Small differences were
      observed in the antigen profiles of the bacteria maintained under the different
      treatments, possibly due to a reduction in the size and metabolism of the
      bacteria. There was also a marked decline in the sensitivity of the PCR with
      bacteria maintained under the different treatments 14 wk from the onset of the
      study.

PMID- 14598988
TI  - Pharmacokinetics of florfenicol in cod Gadus morhua and in vitro antibacterial
      activity against Vibrio anguillarum.
AB  - The pharmacokinetic profile of the antibacterial agent florfenicol was studied in
      plasma after intravenous (i.v.) injection and in plasma, muscle and liver
      following oral (p.o.) administration to cod Gadus morhua, held in seawater at 8
      degrees C and weighing 100 to 200 g. Following i.v. injection, the plasma drug
      concentration-time profile showed 2 distinct phases. The plasma distribution half
      life (t1/2alpha) was estimated to be 1.6 h, the elimination half-life (t1/2beta)
      to be 43 h, the total body clearance (ClT) to be 0.015 1 kg(-1) h(-1) and mean
      residence time (MRT) to be 74 h. The volume of distribution at steady state,
      Vd(ss), was calculated to be 1.1 l kg(-1). Following p.o. administration, the
      bioavailability was estimated to be 91%, the peak plasma concentrations (Cmax) to
      be 10.8 microg ml(-1) and the time to peak plasma concentrations (Tmax) to be 7
      h. Corresponding Cmax and Tmax values were 13.0 microg g(-1) and 9 h,
      respectively, in muscle and 12.1 microg g(-1) and 9 h, respectively, in liver.
      The in vitro minimum inhibitory concentration (MIC) values of florfenicol against
      3 Vibrio anguillarum strains isolated from diseased cod (A-21, HI-610, HI-618)
      were 0.5 microg ml(-1) for all 3 strains.

PMID- 14598989
TI  - Exposure to Thiodan results in lipofuscin accumulation in hepatocytes of the
      freshwater catfish Tandanus tandanus.
AB  - We investigated the effect of time after pulse exposure to 1.0 microg l(-1)
      endosulfan (applied as Thiodan) on endosulfan residues in the liver and
      ultrastructural changes in the hepatocytes of the freshwater catfish Tandanus
      tandanus. Time after exposure did not affect the mean residue level in the liver.
      After exposure to endosulfan, residues in the liver were 227.47 microg kg(-1)
      after 1 d and 282.83 microg kg(-1) after 28 d; residues in the bile were 313.97
      microg kg(-1) after 1 d and 334.53 microg kg(-1) after 28 d. At the end of 28 d
      exposure, lipofuscin was present in up to 69% of hepatocytes of fish containing
      residues of endosulfan, but absent from control fish. There was a statistically
      significant increase in the percentage of pyknotic nuclei and altered rough
      endoplasmic reticulum 28 d after exposure. The mean percentage of cells with
      altered endoplasmic reticulum ranged from 12.93% (Day 1) to 7.50% (Day 28) for
      control fish, while for exposed fish it increased from 14.30% (Day 1) to 35.00%
      (Day 28). The mean percentage of cells with pyknotic nuclei increased from 1.1 to
      2.1% in control fish and from 3.8 to 9.6% in exposed fish. Other ultrastructural
      changes included increased ultrastructural heterogeneity, progressive vacuolation
      and fractionation of rough endoplasmic reticulum, accumulation of lysosomes and
      residual bodies, intranuclear inclusions and pseudoinclusions, membrane whorls
      and myelinated bodies. Protracted senescence was one of the main features of
      endosulfan toxicity to T. tandanus hepatocytes.

PMID- 14598990
TI  - Mapping multiple genetic loci associated with Ceratomyxa shasta resistance in
      Oncorhynchus mykiss.
AB  - Ceratomyxa shasta is enzootic to some rivers of the Pacific Northwest and
      California, and has caused extensive mortalities of salmonids, the only known
      host of the actinosporean stage of the pathogen. Mortalities from C. shasta are
      induced by severe inflammation and necrosis of the intestinal tract, and no
      therapeutants have been discovered for the treatment of ceratomyxosis.
      Inheritance studies by previous investigators suggested that C. shasta resistance
      is genetically controlled, but none have revealed the number and locations of
      gene regions associated with resistance. Here, we characterized differences in
      resistance among clonal lines, and used line crosses between clonal lines with
      resistance differences for a genetic analysis of C. shasta resistance in
      Oncorhynchus mykiss, following a short term in situ exposure to the pathogen. We
      found that Oregon State University (OSU) x Arlee (ARL) clonal hybrids were highly
      susceptible, while OSU x Clearwater (CW) hybrids were highly resistant to C.
      shasta. Doubled haploids, produced by androgenesis from an F1 hybrid between the
      OSU and CW lines, were evaluated for the co-segregation of molecular markers and
      resistance phenotype. Amplified fragment length polymorphic (AFLP) markers, used
      to construct a genetic linkage map in this cross, were tested for associations
      with resistance expressed as absolute survival (binary trait) and days to death
      (survival analysis). Segregation of the resistance phenotype suggested that the
      resistance was inherited as a single Mendelian locus, but the binary trait failed
      to map to a single genomic location. Markers identified in single-marker analyses
      were used in multiple-regression model selection, within both the linear
      regression and Cox proportional-hazards survival analysis frameworks, to
      determine the number and potential location of loci simultaneously contributing
      to variation in the survival phenotypes of doubled-haploid progeny. We found
      multiple genomic loci associated with C. shasta resistance through these models,
      confirming studies by previous investigators that suggested C. shasta resistance
      is polygenic.

PMID- 14598991
TI  - Intracellular infection with Spironucleus barkhanus (Diplomonadida: Hexamitidae)
      in farmed Arctic char Salvelinus alpinus.
AB  - A case of intracellular systemic infection with the diplomonad flagellate
      Spironucleus barkhanus in farmed Arctic char Salvelinus alpinus is described. The
      parasites were widely disseminated throughout the vasculature and in most organs.
      Aggregates of the parasites were seen within well-defined structures regarded as
      host cells in capillaries and sinusoids of the liver, spleen and head kidney.
      Intracellular infection with Spironucleus spp. has never previously been
      reported. The prevalence of infection and mortality in the affected farm was low.
      In contrast to systemic spironucleosis in farmed Atlantic salmon, and despite
      huge numbers of flagellates in the vasculature, the tissues of the organs were
      remarkably unaffected. The relatively few gross and histopathological lesions may
      indicate that Arctic char are more tolerant to this parasite than Atlantic
      salmon.

PMID- 14598992
TI  - Apoptosis in the pathogenesis of infectious diseases of the eastern oyster
      Crassostrea virginica.
AB  - Apoptosis, or programmed cell death, has been reported as being pivotal in
      infectious diseases of different organisms. The effects of apoptosis on the
      progression and transmission of the protistan parasites Perkinsus marinus and
      Haplosporidium nelsoni in the eastern oyster Crassostrea virginica were studied.
      Oysters were diagnosed for their respective infections by standard methods, and
      apoptosis was detected using in situ hybridization to detect DNA fragments by end
      labeling on paraffin sections. A digoxigenin nucleotide probe was used to label
      the 200 bp fragment produced by apoptosis and detected immunohistochemically
      using an antidigoxigenin peroxidase conjugate. The probe/DNA fragment complex was
      stained with a peroxidase substrate and tissues were counterstained with methyl
      green. Uninfected oysters had large numbers of apoptotic hemocytes present in the
      connective tissue underlying the stomach, gill, and mantle epithelia, whereas
      oysters infected with P. marinus had a reduced number of apoptotic hemocytes. The
      parasite may prevent hemocyte apoptosis in order to yield a greater number of
      hemocytes in which to house itself. Large numbers of P. marinus cells in some
      infected oysters were eliminated via apoptosis in the stomach epithelia,
      disabling the spread of infectious particles through seawater. The oysters
      infected with H. nelsoni also had reduced numbers of apoptotic hemocytes, while
      part of the vesicular connective tissue cells were apoptotic. H. nelsoni
      plasmodia were eliminated via apoptosis in some oysters. Apoptosis may enhance
      progression and prevent transmission of infectious oyster diseases.

PMID- 14598993
TI  - Epidemiology of tattoo skin disease in bottlenose dolphins Tursiops truncatus
      from the Sado estuary, Portugal.
AB  - We report on the epidemiology of tattoo disease in a community of bottlenose
      dolphins Tursiops truncatus from the Sado estuary, Portugal. The presence of
      tattoos (T++) and tattoo-like (T+) lesions was examined in 586 photographic
      records of 35 dolphins taken from 1994 to 1997. Images were rated into 3
      categories: good (GI), average (AI) and poor (PI). Dolphins positive for T++
      lesions were observed in 19 GI. Dolphins with T+ lesions were seen in 39 GI, 23
      AI and 6 PI. For statistical analysis the dolphins were divided into 2 age
      classes (immature and adult) and the data grouped into 2 periods (1994-1995 and
      1996-1997). Minimum prevalence of T++ lesions in 32 dolphins was 21.9% in 1994
      1995 and 15.6% in 1996-1997. Variation in prevalence of tattoo disease between
      the 2 age classes was examined for each period, excluding animals with T+ lesions
      or considering them either positive or negative for tattoos. Prevalence of the
      disease was significantly higher in immature dolphins than in adults during both
      periods, except in the first one when T+ lesions were considered as true tattoos.
      Temporal variation in prevalence of tattoo disease was examined in 23 adults.
      Prevalence was significantly higher in 1994-1995 (39.1%) than in 1996-1997
      (17.4%). Differences in the number and quality of pictures did not cause
      significant biases that could have favoured the detection of lesions between age
      classes or periods. Minimal persistence of the disease ranged between 3 and 45.5
      mo. The lesions converted into light grey marks when healing, but may recur. The
      presence of very large lesions in 2 adult dolphins affected for years may be
      related to the contamination of the estuary. The high prevalence of the disease,
      its long persistence, as well as higher frequency in immature individuals,
      suggest that it is endemic in bottlenose dolphins from the Sado estuary. The
      contribution of tattoo disease to the decline of this community should be
      investigated. Three of the 5 dolphins that died during this study had T++ and T+
      lesions.

PMID- 14598994
TI  - Antibodies against Discocotyle sagittata (Monogenea) in farmed trout.
AB  - The relationship between Discocotyle sagittata intensities and host length,
      weight and specific anti-parasite antibody titres was studied in 3 year-classes
      of farmed rainbow trout Oncorhynchus mykiss and brown trout Salmo trutta at the
      end of the annual transmission cycle. Antibody titres were significantly higher
      in infected farmed fish than in naive controls, indicating that infection elicits
      immunoglobulin production. No correlation was found between host size and
      parasite burdens, nor between infection intensities and antibody titres.

PMID- 14598995
TI  - Selection by consequences: one unifying principle for a transdisciplinary science
      of prevention.
AB  - The principle of selection by consequences is critical to the analysis of a broad
      range of phenomena in the biological and behavioral sciences from the evolution
      of species to the selection of cultural practices. This paper reviews the role of
      that principle in diverse areas of the biobehavioral sciences and discusses how
      it can provide one dimension along which the diverse disciplines relevant to the
      prevention of problems of human behavior can be integrated. Such integration
      should improve the ability of prevention science to reduce the incidence and
      prevalence of human behavior problems.

PMID- 14598996
TI  - Culturally grounded substance use prevention: an evaluation of the keepin' it
      R.E.A.L. curriculum.
AB  - This paper reports on the evaluation of a culturally grounded prevention
      intervention targeting substance use among urban middle-school students. The
      curriculum consists of 10 lessons promoting antidrug norms and teaching
      resistance and other social skills, reinforced by booster activities and a media
      campaign. Three versions were delivered: Mexican American, combined African
      American and European American, and Multicultural. Thirty-five middle schools
      were randomly assigned to 1 of the 3 versions or the control. Students completed
      baseline and follow-up questionnaires over a 2-year period (total 6,035
      respondents). Analyses utilizing a generalized estimating equations approach
      assessed the overall effectiveness of cultural grounding and the cultural
      matching hypothesis. Support was found for the intervention's overall
      effectiveness, with statistically significant effects on gateway drug use as well
      as norms, attitudes, and resistance strategies but with little support for the
      cultural matching hypothesis. Specific contrasts found the Mexican American and
      Multicultural versions impacted the most outcomes.

PMID- 14598997
TI  - Factorial invariance in preventive intervention: modeling the development of
      intelligence in low birth weight, preterm infants.
AB  - The paper addresses the issue of measurement invariance in the analysis of
      preventive intervention data. Procedures for testing the invariance of covariance
      matrices, measurement models, and structural growth models are illustrated using
      data from an early intervention program for low birth weight, preterm infants.
      Intelligence Quotient (IQ) measured at 5 time points was modeled using piecewise
      growth curve analysis. Change over time in children's cognitive development was
      modeled separately for the pre- and postintervention periods. The first period
      was during the intervention, which lasted from birth through age 3 years. The
      second was during the postintervention period, which included follow-up
      assessments at ages 5 and 8 years. The analytical approach is illustrated with
      findings indicating that the development of IQ was different for higher low birth
      weight (HLBW: 2001-2500 g) and lower low birth weight (LLBW: <2001 g) infants.
      Examination of the effects of covariates on the IQ trajectories associated with
      the two birth weight groups indicated differential effects on IQ depending on the
      period of development and birth weight. Neonatal health and maternal age were
      predictors of IQ change in the LLBW group whereas maternal education was related
      to change in the HLBW group. During the posttreatment period, only Hispanic
      ethnicity and treatment group status were related to change. Hispanic
      participants exhibited an accelerated trajectory between program end and age 8
      years. Intervention recipients exhibited a flatter trajectory during the same
      time period whereas participants in the control group exhibited an accelerated
      development, essentially catching up with their counterparts in the treatment
      group. Results clearly illustrate the utility of invariance testing in modeling
      developmental trajectories in response to preventive intervention.

PMID- 14598998
TI  - Identification of strategies for promoting condom use: a prospective analysis of
      high-risk African American female teens.
AB  - Condom promotion strategies for adolescents typically include provision of
      STD/HIV-associated knowledge, fostering favorable attitudes toward condom use,
      promoting positive peer norms regarding condom use, improving condom-related
      communication skills and self-efficacy, and overcoming barriers to condom use.
      The purpose of this study was to identify which of these constructs were
      prospectively associated with condom use among a high-risk sample of African
      American adolescent females reporting sexual activity with a steady male partner.
      Adolescents, 14-18 years old, were recruited from schools and health clinics.
      Adolescents completed an in-depth survey and interview at baseline and again 6
      months later. Analyses were limited to adolescents with steady partners who
      reported sexual activity between the baseline and 6-month follow-up assessment
      periods (N = 179). At baseline, five-scale measures and a single-item measure
      were used to assess predictive constructs. At follow-up, adolescents were asked
      about their frequency of condom use over various periods of recall. Multivariate
      models were created to control for the confounding influence of pregnancy status.
      The findings were remarkably distinct. The evidence strongly supported the
      predictive role of perceived barriers toward condom use and peer norms. The
      measure of sexual communication achieved significance for two of the six assessed
      outcomes. Alternatively, measures of attitudes toward condom use, condom
      negotiation self-efficacy, and knowledge about STD/HIV-prevention were
      consistently nonsignificant. The findings suggest that to improve effectiveness
      of individual-level STD/HIV prevention programs, designed for this population,
      program emphasis should be on reducing barriers to condom use, teaching partner
      communication skills, and fostering positive peer norms relevant to condom use.

PMID- 14598999
TI  - Dissemination of an evidence-based prevention innovation for aggressive children
      living in culturally diverse, urban neighborhoods: the Early Risers effectiveness
      study.
AB  - This study evaluated the effectiveness of the Early Risers "Skills for Success"
      Program when implemented by neighborhood family resource centers available to
      urban children and their families. Kindergarten and first-grade children (n =
      327) enrolled in 10 schools were screened for aggressive behavior, and randomized
      to two model variations of the Early Risers Program or a no-intervention control
      condition. The full-strength model (CORE + FLEX) included child and parent/family
      components whereas the partial model (CORE-only) offered only the child
      component. The intervention was delivered over two continuous years. CORE + FLEX
      children showed higher levels of program attendance than their CORE-only
      counterparts but no differences on outcomes measures were observed between
      models. When both program models were collapsed and compared to controls, program
      children showed significant gains on measures of school adjustment and social
      competence, the most aggressive program children showed reductions in disruptive
      behavior, and program parents reported reduced levels of stress.

PMID- 14599000
TI  - Mailed feedback reduces consumption among moderate drinkers who are employed.
AB  - To test the efficacy of mailed feedback for drinking reduction among employees of
      a manufacturing firm, 48 drinkers were recruited and alternately assigned to
      receive mailed feedback on their drinking either immediately or after an 8-week
      waiting period. Using a delayed treatment design, participants were assessed by
      mail at baseline, 8, and 16 weeks. After viewing their feedback, participants
      indicated a higher level of importance of making a change, but not confidence in
      their ability. There were also significant decreases in consumption after
      receiving the feedback, and these changes were mediated by participants'
      increased perceptions regarding the "riskiness" of alcohol consumption. An
      additional 26 nondrinkers at baseline volunteered to participate and also were
      mailed feedback. Among this group, receipt of feedback indicating a very low
      level of risk did not lead to increased drinking. This cost-effective
      intervention appears to reduce consumption among light-to-moderate drinkers, and
      may warrant a larger place in the framework of workplace alcohol reduction
      programs.

PMID- 14599001
TI  - Statistical analysis of functional magnetic resonance imaging data: current state
      and recent developments.

PMID- 14599002
TI  - Wavelets and statistical analysis of functional magnetic resonance images of the
      human brain.
AB  - Wavelets provide an orthonormal basis for multiresolution analysis and
      decorrelation or 'whitening' of nonstationary time series and spatial processes.
      Wavelets are particularly well suited to analysis of biological signals and
      images, such as human brain imaging data, which often have fractal or scale
      invariant properties. We briefly define some key properties of the discrete
      wavelet transform (DWT) and review its applications to statistical analysis of
      functional magnetic resonance imaging (fMRI) data. We focus on time series
      resampling by 'wavestrapping' of wavelet coefficients, methods for efficient
      linear model estimation in the wavelet domain, and wavelet-based methods for
      multiple hypothesis testing, all of which are somewhat simplified by the
      decorrelating property of the DWT.

PMID- 14599003
TI  - Detecting activation in fMRI data.
AB  - We present a simple approach to the analysis of fMRI data collected from several
      runs, sessions and subjects. We take advantage of the spatial nature of the data
      to reduce the noise in certain key parameters, achieving an increase in degrees
      of freedom for a mixed effects analysis. Our main interest is the analysis of the
      resulting images of test statistics using the geometry of random fields. We show
      how the Euler characteristic of the excursion set plays a key role in setting the
      threshold of the image to detect regions of the brain activated by a stimulus.

PMID- 14599004
TI  - Controlling the familywise error rate in functional neuroimaging: a comparative
      review.
AB  - Functional neuroimaging data embodies a massive multiple testing problem, where
      100,000 correlated test statistics must be assessed. The familywise error rate,
      the chance of any false positives is the standard measure of Type I errors in
      multiple testing. In this paper we review and evaluate three approaches to
      thresholding images of test statistics: Bonferroni, random field and the
      permutation test. Owing to recent developments, improved Bonferroni procedures,
      such as Hochberg's methods, are now applicable to dependent data. Continuous
      random field methods use the smoothness of the image to adapt to the severity of
      the multiple testing problem. Also, increased computing power has made both
      permutation and bootstrap methods applicable to functional neuroimaging. We
      evaluate these approaches on t images using simulations and a collection of real
      datasets. We find that Bonferroni-related tests offer little improvement over
      Bonferroni, while the permutation method offers substantial improvement over the
      random field method for low smoothness and low degrees of freedom. We also show
      the limitations of trying to find an equivalent number of independent tests for
      an image of correlated test statistics.

PMID- 14599005
TI  - What can modern statistics offer imaging neuroscience?
AB  - This paper presents a mixed-effects model, region-of-interest analysis of a
      longitudinal functional magnetic resonance imaging (fMRI) study of drug effects
      on human memory function. A key region of interest is the human hippocampus,
      affected by brain disorders such as Alzheimer's disease and schizophrenia. A
      brief section on human hippocampal cell microscopy complements the discussion of
      the macroscopic fMRI study. Statistical issues confronted in these two
      applications are then placed in a broader context for further discussion of the
      future roles of biostatisticians and our methods in the fertile intersection of
      applied mathematical abstraction and imaging neuroscience. Neuroscientific and
      fMRI background is provided for readers new to either area.

PMID- 14599006
TI  - Nucleation-elongation: a mechanism for cooperative supramolecular polymerization.
AB  - The kinetic and thermodynamic characteristics of polymerizations following a
      cooperative, nucleation-elongation mechanism are discussed in comparison to those
      of non-cooperative, isodesmic polymerizations. Nucleation-elongation
      polymerization is a relatively unexplored avenue of synthetic polymer chemistry
      and offers some unique and interesting thermodynamic and kinetic attributes not
      found in the more classical mechanisms of polymer chemistry.

PMID- 14599007
TI  - A rapid stereocontrolled synthesis of the 3a-hydroxy-pyrrolo[2,3-b]indole
      skeleton, a building block for 10b-hydroxy-pyrazino[1',2':1,5]pyrrolo[2,3
      b]indole-1,4-diones.
AB  - A two-step selenocyclisation-oxidative deselenaton sequence was used to establish
      the 3a-hydroxy-pyrrolo[2,3-b]indole core; these tricycles were used as effective
      precursors to 10b-hydroxy-pyrazino[1',2':1,5]pyrrolo[2,3-b]indole-1,4-diones.

PMID- 14599008
TI  - A general synthetic route to 1-azabicyclo[m.n.0]alkenes via cyclisation based on
      alpha-sulfinyl carbanions.
AB  - The intramolecular nucleophilic addition of alpha-sulfinyl carbanions derived
      from the corresponding sufinyl lactams afforded 1-azabicyclo[m.n.0]alkenes in
      good yields.

PMID- 14599009
TI  - The mechanism of 7,8-diaminopelargonate synthase; the role of S
      adenosylmethionine as the amino donor.
AB  - The product of the first transamination step in the reaction catalysed by
      diaminopelargonate (DAPA) synthase has been shown to be 4-(S-adenosyl)-2
      oxobutanoate, which has been trapped as the corresponding alcohol.

PMID- 14599010
TI  - The first fluorogenic assay for detecting a Baeyer-Villigerase activity in
      microbial cells.
AB  - The first fluorogenic assay allowing for detection of microbial enzymes able to
      perform Baeyer-Villiger oxidation is described. This is based on the use of 4
      oxopentyl umbelliferyl ether 1 as a fluorogenic substrate. When Baeyer
      Villigerases active against this test ketone are present in the selected whole
      cells, 1 is transformed into 3-hydroxypropyl umbelliferyl ether 3, which, in a
      subsequent step, releases the fluorescent product umbelliferone. Different
      microorganisms, known to be endowed with Baeyer-Villigerase activity, were
      assayed.

PMID- 14599011
TI  - Cholic acid as template for multivalent peptide assembly.
AB  - Cholic acid, an amphiphilic steroid containing several selectively addressable
      functionalities, was exploited as a rigid template for multivalent peptide
      assembly. Thus, cholic acid-based templates suitable for chemoselective peptide
      ligation were synthesized, in which maleimide or bromoacetyl moieties were
      selectively introduced at the 3alpha, 7alpha, 12alpha-positions of cholic acid
      with varied length of linkers. Three peptides were chosen and tested for the
      chemoselective ligation. These include the HIV-1 peptide inhibitor DP178, the
      universal T-helper epitope derived from tetanus toxoid (830-844), and the minimum
      epitope sequence of the HIV-neutralizing antibody 2F5. It was found that the
      maleimide-functionalized templates are highly efficient for the ligation of all
      the peptides, while bromoacetyl templates led to low yield of ligation. Circular
      dichroism (CD) spectroscopic studies of the multivalent peptides (10a and 11a)
      containing three strands of peptide DP178 indicate that the template-assembled
      peptides form three alpha-helix bundles with significantly enhanced alpha-helix
      contents than the single peptide. The results suggest that cholic acid is a
      valuable template for constructing alpha-helix bundles that may be useful as
      mimics of conformational epitopes for vaccine development.

PMID- 14599012
TI  - 2'-Spiro ribo- and arabinonucleosides: synthesis, molecular modelling and
      incorporation into oligodeoxynucleotides.
AB  - We have synthesized four conformationally restricted bicyclic 2'-spiro
      nucleosides via 2'-C-allyl nucleosides as key intermediates. The ribo-configured
      2'-spironucleosides 9b and 14b were obtained by a convergent strategy starting
      from 2-ketofuranose 1 whereas the arabino-configured 2'-spironucleosides 21 and
      27 were obtained by a linear strategy with a 2'-ketouridine derivative as
      starting material. The furanose ring of 9b/14b adopts N-type conformations
      whereas the furanose ring of 21/27 exists as an N<==>S equilibrium. These
      compounds showed no anti-HIV-1 activity or cytotoxicity. Incorporation of the
      four 2'-spironucleosides (as monomers X4 and X5) into oligodeoxynucleotides was
      accomplished using the phosphoramidite approach on an automated DNA synthesizer.
      Irrespective of monomeric configuration, hybridization studies revealed that
      these 2'-spironucleotide monomers (X4 and X5) induce decreased duplex
      thermostabilities compared with the corresponding DNA:DNA and DNA:RNA duplexes.
      Molecular modelling indicated that steric constraints are a possible reason for
      the lowered binding affinities of the modified oligodeoxynucleotides towards
      complementary single-stranded DNA and single-stranded RNA complements.

PMID- 14599013
TI  - 4-Fluorinated L-lysine analogs as selective i-NOS inhibitors: methodology for
      introducing fluorine into the lysine side chain.
AB  - In the literature, the introduction of fluorine into bioactive molecules has been
      known to enhance the biological activity relative to the parent molecule.
      Described in this article is the synthesis of 4R-fluoro-L-NIL (12) and 4,4
      difluoro-L-NIL (23) as part of our iNOS program. Both 12 and 23 were found to be
      selective iNOS inhibitors as shown in Table 2 below. Secondarily, methodology to
      synthesize orthogonally protected 4-fluoro-L-lysine and 4,4-difluoro-L-lysine has
      been developed.

PMID- 14599015
TI  - Synthesis and evaluation of new potential HIV-1 non-nucleoside reverse
      transcriptase inhibitors. New analogues of MKC-442 containing Michael acceptors
      in the C-6 position.
AB  - Analogues of MKC-442 capable of undergoing Michael addition reactions were
      synthesised in order to investigate the activity against the HIV-1 mutant
      (Y181C). An improved activity was postulated on the basis of a possible covalent
      binding to the mercapto group of Cys181. Lithiation of the C-6 position of 1
      ethoxymethyl-5-ethyl-1H-pyrimidine-2,4-dione (5) was followed by reaction with
      alpha,beta-unsaturated aldehydes and oxidation of the alcohols formed to give the
      alkenoyl analogues 1a-3a. Analogues 1b-3b containing an allyloxymethyl group in
      the N-1 position instead of the ethoxymethyl group could not be synthesised due
      to isomerisation of the allylic group during the metallation reaction. The NMR
      data for compounds 1a-3a showed a hindered rotation, which was more pronounced
      for the 6-cyclohexenylcarbonyl derivative 3a than for the propenyl derivatives 1a
      and 2a. Moderate activity against wild type HIV-1 was observed for the alcohol 8
      and the ketones 2a-3a. However, no activity was observed against the Y181C
      mutant.

PMID- 14599014
TI  - MM-PBSA free energy analysis of endo-1,4-xylanase II (XynII)-substrate complexes:
      binding of the reactive sugar in a skew boat and chair conformation.
AB  - The binding of xylotetraose in different conformations to the active site of endo
      1,4-beta-xylanase II (XynII) from Trichoderma reesei was studied using molecular
      dynamics (MD) simulations and free energy analyses employing the MM-PBSA
      (Molecular Mechanics-Poisson-Boltzmann Surface Area) method. MD simulations of 1
      ns were done for the substrate xylotetraose having the reactive sugar, which is
      bound in the -1 subsite of XynII in the 4C1 (chair) and 2So (skew boat) ground
      state conformations, and for the transition state of the XynII catalysed
      hydrolysis of the beta-glycosidic linkage. According to the simulations and free
      energy analysis, XynII binds the substrate with the -1 sugar in the 2So
      conformation 59.8 kJ mol(-1) tighter than the substrate with the sugar in the 4C1
      conformation. The reactive 2So conformation resembles closely the reaction
      transition state and has the breaking glycosidic bond in a pseudo-axial
      orientation ready for facile bond cleavage. The transition state was calculated
      to be bound 77.1 kJ mol(-1) tighter than the 4C1 ground state conformation. The
      molecular mechanical interaction energy between the enzyme and the reactive
      pyranoside unit at the -1 subsite was 75.7 kJ mol(-1) more favorable for the
      binding of the 2So conformation than the 2C1 conformation, explaining the clearly
      tighter binding of the reactive structure The results of this study indicate that
      in the Michaelis complex XynII, a member of the family 11 xylanase, the substrate
      is bound in a skew boat conformation and in the catalytic reaction, the -1 sugar
      proceeds from the 4C1 conformation through 2So to the transition state with the 
      1 sugar in the 2,5B conformation.

PMID- 14599016
TI  - Synthesis of D- and L-myo-inositol 1,2,4,6-tetrakisphosphate, regioisomers of myo
      inositol 1,3,4,5 tetrakisphosphate: activity against Ins(1,4,5)P3 binding
      proteins.
AB  - We report here the synthesis of D- and L-myo-inositol 1,2,4,6-tetrakisphosphate
      3a and 3b and the racemic modification 3ab. Racemic myo-inositol 1,2,4,6
      tetrakisphosphate 3ab was synthesised from DL-1,2,4,6-tetra-O-allyl-myo-inositol
      9ab. Benzylation and de-allylation provided the tetraol 11ab, which was
      phosphitylated in the presence of bis(benzyloxy)diisopropylaminophosphine and 1H
      tetrazole, then oxidised to give the fully protected 1,2,4,6-tetrakisphosphate
      13ab. Hydrogenolysis of 13ab and purification of product by ion exchange
      chromatography gave racemic myo-inositol 1,2,4,6-tetrakisphosphate 3ab, which
      showed no demonstrable agonism or antagonism for Ca2+ release at 200 microM in
      permeabilised hepatocytes. The chiral derivatives, D-3a and L-myo-inositol
      1,2,4,6-tetrakisphosphate 3b were synthesised from 5-O-benzyl-1,4,6-tri-O-p
      methoxybenzyl-myo-inositol 19ab, which was resolved using R-(-)-O-acetylmandelic
      acid providing two diastereoisomers 21 and 22 which were separated and deacylated
      to give the corresponding enantiomers. Further transformations gave the
      corresponding chiral 1,2,4,6-tetraols which were phosphitylated, oxidised,
      deprotected and purified as for the racemic mixture. The enantiomeric
      tetrakisphosphates 3a and 3b were evaluated for inhibition of the metabolic
      enzymes inositol 1,4,5-trisphosphate 5-phosphatase and 3-kinase in comparison
      with the enantiomers of another synthetic regioisomer D- and L-myo-inositol
      1,2,4,5-tetrakisphosphate. Both D- and L-myo-inositol 1,2,4,6-tetrakisphosphate
      inhibit 5-phosphatase with an IC50 value of 3.8 microM and 14 microM,
      repectively. However, both enantiomers were poorly recognised by the 3-kinase
      enzyme, with IC50 values greater than 100 microM. The enantiomers of the 1,2,4,5
      tetrakisphosphate showed the same relative pattern of activity towards the two
      enzymes but were more potent against 5-phosphatase (0.47 microM and 3 microM
      respectively).

PMID- 14599017
TI  - Synthesis of 9-methyl-1H-[1,4]thiazino[3,2-g]quinoline-2,5,10(3H)-trione, the
      B,C,D ring core of the shermilamine alkaloids.
AB  - Synthesis of 9-methyl-1H-[1,4]thiazino[3,2-g]quinoline-2,5,10(3H)-trione (4),
      from N-(4-bromo-2,5-dimethoxyphenyl)acetamide (23) is described. Oxidative
      cyclisation of 2,2'-disulfanediylbis[N-(2,5-dimethoxyphenyl)acetamide] (19) to
      5,8-dimethoxy-2H-1,4-benzothiazin-3(4H)-one (7b) is also reported.

PMID- 14599018
TI  - Enzymatic synthesis of phosphocarnitine, phosphogabob and fosfomycin.
AB  - Phosphocarnitine was conveniently obtained from easily available diethyl 3-chloro
      2-oxopropanephosphonates, followed by subsequent reduction, Mucor miehei lipase
      (IM) mediated resolution, amination and dealkylation. Candida antarctica lipase B
      (CALB) served as an effective biocatalyst in the resolution of several 1- or 2
      hydroxyalkanephosphonates. The chlorine atom in different positions on the
      molecules greatly affected their enantioselectivity. CALB also showed
      satisfactory enantioselectivity toward those molecules bearing an azido moiety.
      Both enantiomers of phosphogabob and fosfomycin were also prepared via CALB
      mediated resolution as the key step.

PMID- 14599019
TI  - A tricycloheptane product in cationic rearrangements.
AB  - The bicycloheptene 6 rearranged in acid to give the tricycloheptane 9, as shown
      by an X-ray crystal structure determination of the p-nitrobenzoate 10 derived
      from it. Earlier results in the literature had already indicated that this isomer
      was the thermodynamic sink. This apparently crowded structure, with its three
      contiguous quaternary centres, is, nevertheless, lower in energy than other
      accessible but less crowded structures, because of electronic stabilisation of
      the more substituted cyclopropane ring conjugated to the ester group.

PMID- 14599020
TI  - Enantiospecific synthesis of the phospholipase A2 inhibitors (-)-cinatrin C1 and
      (+)-cinatrin C3.
AB  - The enantiospecific synthesis of (-)cinatrin C1 (3) and (+)-cinatrin C3 (5) from
      the D-arabinose derivative 9 is described. The stereochemistry at C2 was
      introduced via a chelation-controlled addition of a carbanion to alpha-hydroxy
      ketone 8. The best selectivity was achieved by use of the Grignard reagent
      derived from trimethylsilylacetylene. Transformation of the terminal alkyne into
      methyl ester 17 followed by acetal hydrolysis and selective lactol oxidation gave
      cinatrin C1 dimethyl ester (7). Base hydrolysis and acid induced relactonization
      then gave a 1:1 mixture of cinatrins C1 (3) and C3 (5).

PMID- 14599022
TI  - Synthesis of planar chiral ferrocenyl 1,3-diamines and 1,3-amino ethers.
AB  - The efficient syntheses of novel planar chiral 1,3-diamines and 1,3-amino ethers
      with an oxy or amino function directly bound to the cyclopentadienyl ring of
      ferrocene has been developed. The key reaction is the Cu2O promoted substitution
      of (pR)-N,N-diisopropyl-2-iodoferrocenecarboxamide with either phthalimide or
      AcOH to introduce nitrogen or oxygen functionality onto the cyclopentadienyl
      ring. The enantiomerically pure iodoferrocene derivative is available from the
      known enantioselective ortho-lithiation of N,N-diisopropylferrocenecarboxamide
      with n-BuLi-sparteine. In the course of these studies the synthesis of a novel C2
      symmetric C-2 dimer of N,N-dimethyl-1-ferrocenylethylamine was characterised by
      single crystal X-ray diffraction.

PMID- 14599021
TI  - Solution and solid state 13C NMR and X-ray studies of genistein complexes with
      amines. Potential biological function of the C-7, C-5, and C4'-OH groups.
AB  - Parent genistein and its new amine complexes with morpholine and piperazine were
      studied comparatively in the solid and liquid states by X-ray crystallography and
      13C and 15N NMR spectroscopy. Biochanine A and its complexes were used as
      reference. Secondary deuterium isotope effects on 13C chemical shifts in solution
      were studied in parent isoflavones and their morpholine and piperazine complexes
      to aid in evaluation of the electronic distribution in both systems. In addition,
      to quantify the extent of proton transfer as well as to establish strong hydrogen
      bonding of the 7-OH group in a morpholine complex, proton transfer from the 7-OH
      group to the piperazine nitrogen atom was also confirmed by 13C NMR in the solid
      state and by X-ray studies. The effect of 7-OH deprotonation yields a high
      frequency shift of 7-8 ppm on the C-7 carbon atom of the piperazine complex
      whereas it is as large as 12 ppm in the morpholine complex in the solid. The
      former trend is confirmed from solution state concentration studies which also
      show that the isoflavones have a strong tendency to form complexes with bases.
      Depending on the pKa difference between the isoflavones and the base this leads
      either to proton transfer and ion-pair formation or, in the case of a larger pKa
      difference, to a hydrogen bonded ion pair. The concentration studies show
      formation of a 1:1 genistein-piperazine complex in DMSO. Addition of water leads
      to formation of solvent separated ions. The C-5 OH group is involved in strong
      intramolecular hydrogen bonding leading to a pseudo aromatic ring extending the
      aromatic part of the drug pharmacophore. The analysis also suggests the way that
      both the C-7 and C-4' hydroxyl group of genistein may participate in stabilising
      the ternary inhibitor complexes of tyrosine-specific kinases or DNA topoisomerase
      II.

PMID- 14599023
TI  - Stereochemistry of intramolecular Diels-Alder furan (IMDAF) reactions of furyl
      substituted chiral ethanolamides.
AB  - This paper describes the stereoselective outcome of the intramolecular Diels
      Alder furan (IMDAF) reaction of substituted (2S,3S)-ethanolamides 9-13, which
      were synthesised from a furyl substituted cyanohydrin. The latter was obtained
      from 2-furaldehyde with high enantioselectivity by an oxynitrilase catalysed
      addition of hydrogen cyanide. The stereochemistry of the IMDAF products was shown
      to be dependent on the size of the ethanolamide substituents R. Small
      substituents (H, Me, CN) gave exclusively exo-cycloaddition, whereas more bulky
      ones (Ph, Et) gave both evo- and endo-addition, the larger phenyl substituent
      giving a high endo-exo-ratio.

PMID- 14599024
TI  - Construction of medium-ring oxacycloalkenones. Extension towards benzo-fused
      cyclic ethers.
AB  - Application of the intramolecular Kulinkovich cyclopropanation of oxa-omega
      alkenoic esters followed by Saegusa oxidation and dehydrohalogenation led to
      simple or benzo-fused oxacycloalkenones, basic structural elements in a wide
      range of naturally occurring compounds.

PMID- 14599025
TI  - The surprising nucleophilic addition of aminochlorocarbenes to diethyl
      acetylenedicarboxylate and to oxalyl chloride: quinolines and
      benzo[1,4]diazepines from N-alkylformanilides and oxalyl chloride in the presence
      of Hunig's base.
AB  - Vilsmeier reagents derived from N-methylformanilides undergo ready deprotonation
      with Hunig's base. In xylene, the derived nucleophilic arylaminochlorocarbenes
      bearing 4-methyl- and 4-methoxy-substituents react with acetylenedicarboxylates
      to give 2-(2-chloro-1,2-bis(ethoxycarbonyl)vinyl)-3,4-bis(ethoxycarbonyl)-1
      methyl-1,2-dihydroquinolines while most derivatives react with oxalyl chloride to
      give substituted 1-methyl-4 phenylbenzo[f][1,4]diazepine-2,3-dicarboxylic
      anhydrides.

PMID- 14599026
TI  - Alkane hydroperoxidation with peroxides catalysed by copper complexes.
AB  - Various copper(I) and copper(II) derivatives, both "simple" ones (copper acetate,
      perchlorate and a complex with CH3CN) and compounds containing N,O-chelating
      ligands, catalyse very efficient (turnover numbers attain 2200) oxidation of
      saturated hydrocarbons with peroxyacetic acid (PAA) or tert-butyl hydroperoxide
      (TBHP) in acetonitrile solution at 60 degrees C. Alkyl hydroperoxide, alcohol and
      ketone are formed, the main product being an alkyl hydroperoxide in the oxidation
      with PAA and an alcohol for the case of TBHP. It has been proposed that the
      oxidation with PAA is induced via the attack of species r* [HO* or CH3C(=O)O*] on
      the alkane, RH. A competitive attack of r* on the solvent, CH3CN, also occurs. It
      has been assumed that in the case of the reaction catalysed by complex
      Cu(CH3CN)4BF4, copper is present mainly in the form of Cu+ cation, and the rate
      limiting step of the oxidation process is the formation of r* via reaction (1):
      CH3C(=O)OOH + Cu+ --> CH3C(=O)O* + HO- + Cu2+ or/and CH3C(=O)OOH + Cu+ -->
      CH3C(=O)O- + HO* + Cu2+ with initial rate W1 = k1[PAA][Cu(CH3CN)4BF4] and k1 =
      1.7 mol(-1) dm3 s(-1) at 60 degrees C. The activity of the Cu-catalyst is
      dramatically changed on a small modification of N,O-chelating ligands in the
      catalyst.

PMID- 14599027
TI  - Evidence for the S(N)2' mechanism in hydrolysis of C60F48: origin of the
      stability of trannulenes.
AB  - The products of hydrolysis of C60F48 (which contains six isolated double bonds)
      by either aq. acetone or aq. THF show that no more than twelve fluorines are
      replaced through nucleophilic substitution, as predicted by the recently
      identified S(N)2' mechanism. Subsequent HF elimination gives fragments containing
      a maximum of six epoxide oxygens. Calculated heats of formation of models for the
      possible initial hydroxy derivatives indicate that there is little energetic
      discrimination between them, so that a complex mixture is likely to be formed.
      Overall the data show that hydrolytic degradation of fluorofullerenes is less
      severe than believed previously, requires a specific motif, and explains the low
      susceptibility of C60F18 towards hydrolysis and the high stability of
      trannulenes.

PMID- 14599029
TI  - Orthopedic trauma surgeon: distinction or extinction?

PMID- 14599028
TI  - The formation of beta-beta structures in lignin biosynthesis--are there two
      different pathways?
AB  - Based on results from 2D NMR studies, both pinoresinol and secoisolariciresinol
      structures were found to be present in native lignin from spruce wood as well as
      in spruce kraft lignin and residual kraft pulp lignin. These two structures
      constitute the major types of beta-beta inter-unit linkages present in spruce
      lignin, but their formation in the lignin polymer may follow different pathways
      leading to their different bonding patterns with the rest of the lignin polymer.
      The mechanisms involved are discussed.

PMID- 14599030
TI  - Design concepts and early utilization of a new femoral interlocking nail.
AB  - Interlocking nails provide excellent stability and control of femoral fractures
      from the hip to the supracondylar regions, yielding excellent clinical results.
      Advances in femoral nail design have provided for increased variability in their
      applications, allowing surgeons to stabilize a wide variety of fractures through
      either antegrade or retrograde nail insertion methods. In the past, nails were
      manufactured to be implanted with a specified insertion technique, requiring the
      surgeon to become facile with multiple nail systems to care for the entire
      spectrum of femoral injuries. A new femoral intramedullary nail system is being
      introduced with the capability of stabilizing both right- and left-sided femoral
      fractures in all 3 modes of interlocking--that is, first-generation antegrade
      nailing, second-generation reconstruction nailing, and retrograde nailing. The
      design and rationale of this system are discussed, and clinical examples of use
      of this new device are provided.

PMID- 14599031
TI  - The inferior arc injury: an addition to the family of complex carpal fracture
      dislocation patterns.
AB  - Traditionally, complex wrist injuries were identified and characterized on the
      basis of observation of bony injury and presumption of soft tissue embarrassment,
      followed by employment of a classification scheme or cumbersome nomenclature. The
      extent of tissue compromise was often underestimated, leading to undertreatment
      and inferior results. This paper encourages physicians to think more
      mechanistically about the pattern of injury by relying on the concept of
      "transverse" force transmission to identify the global extent of wrist trauma. By
      employing a basic understanding of the components of the wrist "system" and
      superimposing the flow of energy through it, one can better grasp these complex
      topics. The standard "greater arc" and "lesser arc" injuries are explained in
      this context. Another recognizable injury pattern in the transverse instability
      spectrum, that of the "inferior arc," is introduced, along with clues for its
      identification. The large fragment and small fragment fracture variants of the
      inferior arc injury are emphasized, and their significance is described. Basic
      evaluation and treatment recommendations for inferior arc injuries are offered.

PMID- 14599032
TI  - Total elbow replacement for distal humerus fractures and traumatic deformity:
      results and complications of semiconstrained implants and design rationale for
      the Discovery Elbow System.
AB  - Recent advances in elbow replacement design have further extended its usefulness
      as an expedient reconstructive method for restoring elbow function following
      trauma. This is particularly true in elderly patients, for whom treatment is
      complicated by the frequent presence of osteoporosis, severe comminution with
      small condylar fracture fragments, and diminished bone-healing capacity. This
      article addresses the role of elbow replacement for fracture, traumatic
      deformity, post-traumatic arthritis, and instability. Indications, techniques,
      and results are presented. Complications of semiconstrained implants are
      presented, and the design rationale for, and examples of, the latest-generation
      Discovery Elbow System (Biomet Orthopedics, Warsaw, Indiana) are discussed.

PMID- 14599033
TI  - Treatment of subtrochanteric femur fractures using a submuscular fixed low-angle
      plate.
AB  - The purpose of this study was to evaluate the results of using fixed low-angle
      plates, inserted submuscularly, for the treatment of subtrochanteric femur
      fractures with regard to femoral neck-shaft angle and union. Twenty patients were
      identified through our orthopedic trauma registry who had subtrochanteric femur
      fractures in which the lesser trochanter was detached or without an intact
      piriformis fossa and who had undergone a repair of their fracture with a
      submuscular fixed low-angle plate device. We studied a radiographic measurement
      of the neck-shaft angle, incidence of varus malunion (5 degrees or more),
      operative time and blood loss, time to radiographic union, and time to clinical
      union. Our results demonstrated that the time to radiographic union averaged 91
      days and time to clinical union averaged 107 days. The average operative time was
      108 minutes (range, 43-170 minutes), and estimated blood loss was 418 mL (range,
      150-800 mL). The average femoral neck-shaft angle on the plated femur was 133
      degrees (range, 125 degrees-145 degrees), as compared with an average of 134
      degrees (range, 124 degrees-145 degrees) on the uninjured femur. There were no
      plate or screw failures or nonunions. Submuscular application of fixed low-angle
      plate devices resulted in anatomic alignment of the femoral neck-shaft angle
      while maintaining low rates of implant failure and high rates of union.

PMID- 14599034
TI  - Periprosthetic femur fractures--a growing epidemic.
AB  - The number of periprosthetic femoral fractures is increasing, and this trend will
      continue. The factors contributing to this epidemic include length of time since
      implantation of the prosthesis; loose stems; aging of the population, leading to
      osteoporosis and a tendency to fall; and the large number of hip arthroplasties
      performed each year. These complex fractures necessitate innovative treatments
      and consideration of the biomechanical impact of the treatments on the entire
      femur. We present a small series of cases in which periprosthetic fractures were
      treated with a variety of techniques, including revision and the use of a cable
      plate, allograft, and an adjustable-angle supracondylar cable plate.

PMID- 14599035
TI  - Monitoring breastfeeding rates in Italy.
AB  - AIM: to determine the rates of initiation and duration of breastfeeding in Italy
      in 1995 and 1999, and to examine the adherence to the ten steps to successful
      breastfeeding recommended by WHO. METHODS: Two cohorts of mothers who delivered
      healthy infants in November 1995 (n = 2400) or November 1999 (n = 3500) were
      interviewed by telephone within 4 wk of delivery when their infants were 3 months
      of age. Type of breastfeeding was classified according to the WHO definitions.
      Adherence to the WHO ten steps was evaluated. RESULTS: Initiation and duration of
      breastfeeding increased during the 1995-1999 period (p < 0.0001). The rate of
      breastfeeding at discharge and when the infants where 3 months of age was 83% and
      42% in 1995, and 89% and 66% in 1999. The rate of exclusive/predominant
      breastfeeding at discharge was higher in 1999 than 1995 (78% vs 72%). CONCLUSION:
      An increase in initiation and duration of breastfeeding through the first 3
      months of age occurred in Italy during the 1995-1999 period, but both
      breastfeeding duration and observance of the WHO's ten steps are not completely
      satisfactory yet.

PMID- 14599036
TI  - Initiation of breastfeeding.
AB  - Breastfeeding is a biological process that is highly influenced by various
      physiological and environmental factors such as the plans for infant feeding of
      pregnant women, their education and work situation, family support and nutrition.
      CONCLUSION: The way in which breastfeeding is initiated in the early postnatal
      period is of importance both for how long the process is likely to continue and
      for the growth of the infant.

PMID- 14599037
TI  - Short duration of breastfeeding and early introduction of cow's milk as a result
      of mothers' low level of education.
AB  - Inappropriate infant feeding including a lack of breastfeeding and the early
      introduction of cow's milk are the most common forms of infant feeding
      malpractice. To evaluate the hypothesis that infant feeding malpractices are
      associated with mothers' low level of education, questionnaires were administered
      to 400 mothers of infants below 12 mo of age divided into 3 groups according to
      their various educational levels. Items included the type of milk given at birth
      and at 1, 3 and 6 mo of age. To investigate the efficacy of paediatricians in
      orienting infant feeding, the same questionnaire was given to 30 paediatricians
      in primary paediatric healthcare, in hospitals or in private practices.
      Initiation of breastfeeding was similar in the three groups. An analysis of the
      data showed that an increasing number of infants born to mothers of low and
      intermediate educational level did not receive exclusive breastfeeding compared
      with those with a higher level of education, a difference that was significant as
      early as 1 mo of age. In infants aged 3 mo, the prevalence of exclusive
      breastfeeding was 37%, 40% and 65% in the three groups, respectively, in relation
      to progressively increasing levels of education. In infants of 6 mo, the
      respective prevalence rates were 13%, 15% and 48%. Early introduction of cow's
      milk showed a similar correlation with educational level. A greater number of
      infants born to mothers with a low level of education received cow's milk at 3 mo
      of age compared with those born to mothers with an intermediate education (12% vs
      5%). A similar difference was observed between the latter group and infants born
      to mothers with a high educational level (0%). This pattern was supported by data
      for infants at 6 mo of age with prevalence rates for cow's milk feeding of 39%,
      20% and 0% in the three groups in association with progressively increasing level
      of educational (p < 0.05). The analysis of the paediatricians' response to the
      questionnaire showed that while physicians know and correctly prescribe age
      related infant nutrition regimens, they are unaware that a substantial number of
      mothers do not comply with what they prescribe. Overall, these data support the
      relationship between a low educational level and infant feeding malpractice and
      suggest that a more effective role should be played by paediatricians in
      supporting an adequate duration of breastfeeding and the use of formula rather
      than cow's milk protein.

PMID- 14599038
TI  - Influence of different types of post-discharge feeding on somatic growth,
      cognitive development and their correlation in very low birthweight preterm
      infants.
AB  - The influence of appropriate post-discharge nutrition on somatic growth and
      cognitive development of very low-birthweight infants in the first year of life
      is currently a major topic in infant nutrition. Appropriate intakes of proteins,
      iodine and the addition of LC-PUFAs (arachidonic acid (AA), docosahexaenoic acid
      (DHA)) in the "right" quantities improve cognitive development and are conducive
      to a good correlation between somatic growth and neurodevelopment. CONCLUSION:
      When mother' milk is not available post-discharge, in addition to more proteins
      and minerals, formula for low-birthweight infants should contain AA and DHA,
      since the endogenous production of these important compounds from the precursors
      can be reduced in the first months of life, chiefly in the very low-birthweight
      infants.

PMID- 14599039
TI  - Hydrolysed proteins in preterm formula: influence on plasma aminoacids, blood
      fatty acids and insulinaemia.
AB  - The data from the present investigation differ from those of the previous study.
      The new version of hydrolysed protein formula did not induce changes in
      insulinaemia or in the insulinaemia/glycaemia ratio in pre- and postprandial
      samples when compared with the intact protein formula. The investigation also
      confirmed that branch chain aminoacids regulate insulin secretion and that the
      length of chain is insulinotropic for fatty acids, while the degree of
      unsaturation is not able to reduce insulin secretion in the newborn baby. This
      could be caused by stimulation of insulin output activated by the C20:5 n 3; the
      effects of fatty acids are probably related more to the variable composition of
      cell membrane than to the fatty acids circulating levels.

PMID- 14599040
TI  - Post-discharge nutrition of the very low-birthweight infant: interim results of
      the multicentric GAMMA study.
AB  - This report presents the interim results up to 12 mo corrected age (c.a.) of a
      multicentric, prospective, controlled study on very low-birthweight infants,
      randomized at 40 wk post-conception in two different groups of formula feeding:
      80 Kcal/dL (group A) vs 70 Kcal/dL (group B) up to 55 wk of postconceptional age.
      Subsequently, all the babies were fed with a follow-on formula, with the
      introduction of solid foods at 6 mo c.a. Weight, length, head circumference and
      neurological conditions with psychomotor development (evaluated by the Griffiths'
      Developmental Scale) were measured at regular intervals and all of these
      parameters were satisfactory in both groups. For growth, in group A there was a
      greater increase in weight in boys at 55 wk and at 6 mo c.a., and small for
      gestational age (SGA) babies had a greater increase in length at 1 y of age,
      while head circumference caught up on growth from week 40 to week 55. Measured by
      the Griffiths' Developmental Scale, the SGA group fed 80 Kcal/dL had a better
      score at 6 mo; similarly boys fed 80 Kcal/dL had a better score at 6 and at 9 mo.
      CONCLUSION: Nutrition of very low birthweight infants post-discharge could have
      an influence on physical growth and on neurodevelopmental outcome. This interim
      report needs to be confirmed at the end of the study.

PMID- 14599041
TI  - Allergic manifestations in very low-birthweight infants: a 6-year follow-up.
AB  - The incidence of allergic manifestations was evaluated from birth until 6 y of
      age in 83 very low-birthweight infants (VLBWIs). In the same period 98 full-term
      babies were followed from birth to 24 mo of life. All the subjects were examined
      by paediatricians to establish the presence of atopic dermatitis (AD),
      gastrointestinal disturbances (GD) and asthma (AS). The incidence of total
      allergic manifestations (31.3%) in VLBWIs was significantly lower than that (52%)
      in 24-mo-old infants, born at full term. The incidence of allergies in VLBWIs did
      not differ at all at the subsequent checks, up to 6 y of age. AD (33.7%) was the
      most common symptom, statistically higher in full-term infants than in VLBWIs
      (7.2%). GD had a similar distribution (8.2% in full-term infants vs 7.2% in
      VLBWIs). AS (16.8%) was significantly higher in VLBWIs than in those born full
      term (10.2%). In the various VLBWI subgroups analysed, AD was more prevalent in
      babies weighing >1000 g and in babies >30 wk of age; the incidence of GD was
      higher in infants weighing <1000 g and in SGA infants, and AS was more prevalent
      in infants weighing <1000 g, in infants <30 wk of age and in babies appropriate
      for gestational age. A family history of allergy was related to a major incidence
      of allergies.

PMID- 14599042
TI  - Intestinal microflora in early infancy: composition and development.
AB  - The neonatal intestinal microbiota is a complex ecosystem composed of numerous
      genera, species and strains of bacteria. This enormous cell mass performs a
      variety of unique activities that affect both the colonic and systemic
      physiology. Its primary activities include nutritive, metabolic, immunological
      and protective functions. Most studies of infants have been based on faecal
      samples using the classical plating techniques with culturing on specific media.
      The limitations of these methods must be taken into account when evaluating the
      varying results of the different studies. The establishment of the gut microbial
      population is not strictly a succession in the ecological sense; it is rather a
      complex process influenced by microbial and host interactions and by external and
      internal factors. The climax intestinal flora is attained in successive stages.
      The foetal intestine is sterile and bathed in swallowed amniotic fluid. Following
      delivery, multiple different antigens challenge the intestine of the newborn. The
      maternal intestinal flora is a source of bacteria for the neonatal gut. The
      bacterial flora is usually heterogeneous during the first few days of life,
      independently of feeding habits. After the first week of life, a stable bacterial
      flora is usually established. In full-term infants a diet of breast milk induces
      the development of a flora rich in Bifidobacterium spp. Other obligate anaerobes,
      such as Clostridium spp. and Bacteroides spp., are more rarely isolated and also
      enterobacteria and enterococci are relatively few. During the corresponding
      period, formula-fed babies are often colonized by other anaerobes in addition to
      bifidobacteria and by facultatively anaerobic bacteria; the development of a
      "bifidus flora" is unusual. In other studies the presence of a consistent number
      of bifidobacteria in infants delivered in large urban hospitals has not been
      demonstrated, whether the babies were bottle fed or exclusively breastfed. The
      predominant faecal bacteria were coliforms and bacteroides. According to these
      studies, environmental factors may be more important than breastfeeding in gut
      colonization after delivery. Environmental factors are indeed extremely important
      for the intestinal colonization of infants born by caesarean section. In these
      infants, the establishment of a stable flora characterized by a low incidence of
      Bacteroides spp. and by the isolation of few other bacteria is consistently
      delayed. In extremely low-birthweight infants, hospitalization in neonatal
      intensive care units, characterized by prolonged antibiotic therapy, parenteral
      nutrition, delayed oral feedings and intubation seems to affect the composition
      of the intestinal microbiota. The gut is colonized by a small number of bacterial
      species; Lactobacillus and Bifidobacteria spp. are seldom, if ever, identified.
      According to the few studies so far performed, the predominant species are
      Enterococcus faecalis, E. coli, Enterobacter cloacae, Klebsiella pneumoniae,
      Staphylococcus epidermidis and Staphylococcus haemolyticus. Hygienic conditions
      and antimicrobial procedures strongly influence the intestinal colonization
      pattern.

PMID- 14599043
TI  - Advances in the modulation of the microbial ecology of the gut in early infancy.
AB  - It is now generally accepted that the microbiota of the human gut may influence
      health and well-being. Lactic acid bacteria are the most important microorganisms
      associated with these beneficial effects and the elevated bifidobacterial count
      may be one of the greatest advantages that breastfed infants have over infants
      fed with milk formulas. Several studies relative to the selective growth
      stimulation of bifidobacteria, both in vitro and in vivo, are reported in this
      review. Over the years, diverse human milk components have been identified as the
      specific factors able to modulate the growth of bifidobacteria. Even if there is
      a certain agreement that the bifidogenic activity of human milk may be based not
      on single growth substances, but on a complex set of interacting factors, the
      present state of knowledge indicates that the use of non-digestible but
      fermentable carbohydrates may be an easy and reliable method to influence the
      growth of lactic acid bacteria. In this context, some of the characteristics of
      the major physiological effects of inulin-type fructans, of galacto
      oligosaccharides, but also of lactoferrin, a milk whey protein fraction with
      purported bifidogenic activity, are briefly examined.

PMID- 14599044
TI  - Prebiotic concept for infant nutrition.
AB  - In the neonatal period, the intestine is colonised in a stepwise process that
      depends on mode of delivery, environmental factors, bacterial interactions, and
      the host itself resulting in a colonisation with a complex heterogeneous
      bacterial flora. Oligosaccharides have been identified as an important prebiotic
      factor of human milk As long as analogues of human milk oligosaccharides are not
      available now and in the near future it is aimed to resemble the prebiotic effect
      of human milk by oligosaccharides from available sources. In the present study in
      preterm infants, a mixture of 90% galacto-oligosaccharides and 10% fructo
      oligosaccharides has been tested. The mixture of GOS/FOS was composed to mimic
      the molecule size distribution of human milk oligosaccharides. Microbiological
      analysis of the faces was performed before and 7, 14, and 28 days after start of
      supplementation and stool characteristics have been recorded. Maltodextrin was
      used as placebo and infants fed human milk have been used as reference. After a
      28 days feeding period, the number of bifidobacteria of the group fed the
      oligosaccharide supplemented formula was in the upper range of the reference
      group whereas the numbers of the group fed the formula supplemented with the
      placebo were in the lower range of the reference group (placebo: 7.9 +/- 0.83 and
      GOS/FOS mixture: 10,0 +/- 2.05 log 10 CFU/g wet stool; reference (M +/- SD): 7.14
      10.7 log 10 CFU/g wet stool). Stool characteristics in the group fed the
      supplemented formula were close to those found in the human milk fed infants. In
      summary, supplementation of a preterm formula with a mixture of galacto- and
      fructo-oligosaccharides has a stimulating effect on the growth of bifidobacteria
      in the intestine and results in more frequent produced and softer stools. Thus,
      prebiotic mixtures such like the studied oligosaccharide mixture might help in
      improving intestinal tolerance to enteral feeding in preterm infants.

PMID- 14599045
TI  - Prebiotics in infant milk formulas: new perspectives.
AB  - In recent years it has become accepted that healthy human intestinal microflora
      may play an important part in priming the infants' systemic and mucosal immunity.
      Dietary modulation of the gut microbiota is a topical area of nutritional
      sciences and the main focus of many current functional foods such as non
      digestible oligosaccharides (NDOs). Fructo-oligosaccharides (FOS) and trans-beta
      galacto-oligosaccharides (TOS) have been claimed to benefit the health of the
      colon by selectively stimulating the growth of bifidobacteria and lactobacilli
      (prebiotic effect). It could be of clinical interest to manipulate colonic flora
      because it is supposed that specific bacteria in the gut microbial microflora
      could promote potentially antiallergenic processes and play a key part in atopic
      disease prevention. Supporting this view is the finding that analysis of the
      composition of the intestinal bacterial populations showed different microbial
      patterns between healthy and allergic individuals. Assuming that non-digestible
      TOS and FOS can affect the intestinal ecosystem beneficially, the opportunity for
      gut flora manipulation arises in bottle-fed infants. New preterm and term infant
      milk formulas, supplemented with a mixture of TOS and FOS as prebiotic
      ingredients induced a significantly higher colonization of bifidobacteria and
      lactobacilli. In the future, selective manipulation of the intestinal microbiota
      might be an approach to novel prophylactic and therapeutic intervention
      strategies of atopy, by redirecting allergic Th-2 responses in favour of Th-1
      responses.

PMID- 14599046
TI  - Effects of a new mixture of prebiotics on faecal flora and stools in term
      infants.
AB  - A double-blind, randomized, controlled study was performed in 90 full term
      infants to evaluate dose-related bifidogenic effects of a new synergistic mixture
      of galacto-oligosaccharides (GOS) and fructo-oligosacharides (FOS). The GOS/FOS
      mixture showed a dose-dependent stimulatory effect on the intestinal growth of
      bifidobacteria. Also stool consistency and faecal pH were positively affected.

PMID- 14599048
TI  - Iron balance and iron nutrition in infancy.
AB  - At birth, the total body iron content is approximately 75 mg/kg, twice that of an
      adult man in relation to weight. During the first 6 mo of life, total iron body
      content increases slightly and exclusive breastfeeding is sufficient to maintain
      an optimal iron balance. Thereafter, iron body content substantially increases
      and the infant becomes critically dependent on dietary iron, provided by
      complementary foods. Numerous factors may contribute to nutritional iron
      deficiency in infancy, the most important being low body iron content at birth,
      blood loss, high postnatal growth rate, and a low amount and/or bioavailability
      of dietary iron. We have documented that the prevalence of iron deficiency
      declined in Italy as iron nutrition improved and that early feeding on fresh
      cow's milk is the single most important determinant of iron deficiency in
      infancy. Healthy full-term infants should maintain optimal iron balance by
      consuming a good diet, which can be summarized as follows: breastfeeding should
      be continued exclusively for at least 5 mo and then together with complementary
      foods containing highly bioavailable iron; infants who are not breastfed or are
      partially breastfed should receive an iron-fortified formula, containing between
      4.0 and 8.0 mg/L iron, from birth to 12 mo of age; fresh cow's milk should be
      avoided before 12 mo of age.

PMID- 14599047
TI  - Pro- and pre-biotics administration in preterm infants: colonization and
      influence on faecal flora.
AB  - Prolonged administration of probiotic in preterm babies induce a rise of specific
      IgA and IgM antibodies against probiotic. This fact explains why presence of
      living germs in stools almost disappeared in spite of continuous administration.
      However some positive influences were observed: decreased ratio of
      aerobic/anaerobic. Increased ratio of gram +/gram - germs. Prebiotic
      administration induces after 28 days a significant increase of faecal
      bifidobacteria and frequency and consistency of stools were more similar to those
      observed in subjects fed with human milk.

PMID- 14599049
TI  - "Minor" feeding problems during the first months of life: effect of a partially
      hydrolysed milk formula containing fructo- and galacto-oligosaccharides.
AB  - BACKGROUND: Colic, regurgitation and constipation are common feeding problems in
      formula-fed infants that might benefit from dietary treatment. A formula
      containing fructo- and galacto-oligosaccharides, partially hydrolysed proteins,
      low levels of lactose and palmitic acid in the beta position and higher density
      has been tested to reduce the occurrence of these symptoms. The aim of this
      prospective study was to describe the effects of such a formula in infants with
      minor gastrointestinal disorders. METHODS: An observational prospective trial
      involving practising Italian paediatricians was performed. Formula fed-infants up
      to 90 d of age with minor gastrointestinal problems such as infantile colics
      and/or regurgitation and/or constipation were enrolled in the study from January
      2001 to May 2001. The study was completed within 14 d of treatment. On days 1, 7
      and 14 the infants were visited by the paediatricians. Parents were given a
      structured diary to record daily episodes of colic, regurgitation and type and
      number of stools. RESULTS: Of the 932 infants enrolled, 604 completed the study.
      Of the 214 infants with colic, 169 (79%) demonstrated a reduction in frequency of
      colic from 4.1 +/- 2.0 per day at the beginning of the study to 2.0 +/- 1.8 at
      the end of the study (I.C. 95%: 1.72-2.39; p < 0.005). A reduction in the number
      of episodes of colic of 1.8 per day at the beginning of the study (I.C. 95%: 1.49
      2.11; p < 0.05) was recorded between day 1 and day 7, and of 0.26 (I.C. 95%: 0.15
      0.37; p < 0.05) between day 7 and day 14. Of the 201 infants with regurgitation
      problems, 141 (70%) demonstrated a reduction of frequency of the symptoms from
      4.2 +/- 2.0 per day at the beginningof the study to 2.1 +/- 2.2 at the end of the
      study (I.C. 95%: 1.75-2.35; p < 0.005). A reduction of 1.87 in the number of
      regurgitation episodes was reported between day 1 and day 7 (I.C. 95%: 1.57-2.16;
      p < 0.05) and of 0.18 (I.C. 95%: 0.06-0.31; p < 0.05) between day 7 and day 14.
      Of the 232 infants with constipation, 147 (63%) demonstrated an increase in the
      daily number of stools of 0.42 (I.C. 95%: 0.5-0.3; p < 0.005). An increase in
      stool frequency of 0.41 (I.C. 95%: 0.51-0.23; p < 0.05) was reported between day
      1 and day 7, and of 0.04 (I.C. 95%: 0.22-0.14; p = ns) between day 7 and day 14.
      Parents' evaluation of the formula was 7.9 +/- 1.8 (score 0-10); 550 parents
      (91%) gave a positive judgement (score > 6). The evaluation by the paediatricians
      of the improvement in symptoms after the treatment was 8.2 +/- 1.5; 574 (95%) a
      positive effect (score > 6). CONCLUSION: This study shows that the majority of
      infants followed by paediatricians for minor gastrointestinal symptoms improve
      within 2 wk of feeding with this new formula. Further double-blind, controlled
      studies are needed to confirm whether the amelioration of symptoms observed in
      this trial is in fact due to the new formula.

PMID- 14599050
TI  - Oligosaccharides might stimulate calcium absorption in formula-fed preterm
      infants.
AB  - Among other components of human milk, oligosaccharides might contribute to the
      high efficiency of calcium absorption of breastfed infants. In adults, it can be
      shown that dietary oligosaccharides can improve calcium absorption. The present
      analysis was performed to evaluate a possible influence of dietary
      oligosaccharides on parameters of calcium metabolism in preterm infants. The
      concentrations of calcium and phosphorus in plasma and in spot urine samples as
      well as the plasma activity of the alkaline phosphatase were measured in preterm
      infants fed either a standard formula (n = 15) or a formula supplemented with
      dietary oligosaccharides (n = 15) at the end of a 4-wk feeding period.
      CONCLUSIONS: There was no influence of the different diets on the plasma
      concentration of calcium and phosphorus or on the plasma activity of alkaline
      phosphatase. In urine, there was a tendency towards higher calcium concentrations
      in the group fed the supplemented formula compared concentrations in the group
      fed the standard formula. The concentrations of phosphate were not significantly
      different and, as a consequence, there was a tendency towards a higher Ca/P molar
      ratio in the group fed the supplemented formula. The data indicate that the
      calcium absorption might be influenced by the dietary oligosaccharides. Thus, the
      possible effect of dietary oligosaccharides on calcium homeostasis should be
      included in the discussion concerning the consequences of the use of dietary
      oligosaccharides in preterm infant nutrition.

PMID- 14599051
TI  - Soy-based formulas and phyto-oestrogens: a safety profile.
AB  - Phyto-oestrogens are non-steroidal plant-derived compounds that possess
      oestrogenic activity and act as selective oestrogen receptor modulators (SERMs).
      Among the dietary oestrogens, the isoflavone class enjoy a wide-spread
      distribution in most of the members of the Leguminosae family, including such
      prominent high-content representatives as soybean. Phyto-oestrogen research has
      grown rapidly in recent years owing to epidemiological studies suggesting that
      diets rich in soy may be associated with potential health benefits. There is a
      paucity of data on endocrine effects of soy phytochemicals during infancy, the
      most sensitive period of life for the induction of toxicity. The safety of
      isoflavones in infant formulas has been questioned recently owing to reports of
      possible hormonal effects. Infants fed soy formula receive high levels of phyto
      oestrogens in the form of isoflavones (genistein, daidzein and their glycosides).
      To date, no adverse effects of short- or long-term use of soy proteins have been
      observed in humans and exposure to soy-based infant formulas does not appear to
      lead to different reproductive outcomes than exposure to cow milk formulas. Soy
      formula seems to be a safe feeding option for most infants. Nevertheless, much
      closer studies in experimental animals and human populations exposed to phyto
      oestrogen-containing products, and particularly soy-based infant formulas, are
      necessary.

PMID- 14599052
TI  - Hepatitis and cholestasis in infancy: clinical and nutritional aspects.
AB  - A major complication of cholestasis is fat malabsorption related to decreased
      intestinal bile acids, which leads to malnutrition and fat-soluble vitamin
      deficiency. The impaired excretion of bile acids leads to a low intraluminal
      micellar concentration that causes long-chain triglyceride lipolysis and
      absorption to be ineffective. Medium-chain triglycerides (MCTs) are more readily
      absorbed when there are low concentrations of bile acids and therefore are a good
      source of fat calories; MCTs can be administered as MCT-containing formulas. In
      those children who are unable to take sufficient calories by mouth, it is
      important to start nocturnal enteral feeding to improve nutritional status. In
      infants with cholestasis, the absorption of fat-soluble vitamins (A, D, E and K)
      that require bile acids is also impaired, and supplementation is mandatory.
      Vitamin K deficiency may be responsible for hypoprothrombinaemia, which may lead
      to bleeding diathesis, Vitamin K (phytomenadione) should therefore be promptly
      administered intravenously, at a dose of 1 mg. Chronic vitamin E (alpha
      tocopherol) deficiency is associated with a progressive neuromuscular syndrome
      that can cause cerebellar ataxia, areflexia and peripheral neuropathy.
      Supplements are given orally in doses of 3-5 times the normal requirement if
      cholestasis is incomplete. In complete cholestasis, supplements must be given
      intramuscularly at monthly intervals. In infants who fail to thrive, dietary
      supplements of carbohydrate polymers and MCTs are required.

PMID- 14599053
TI  - Vertical transmission of HIV-1 infection and dilemma of infant feeding.
AB  - The problem of giving proper recommendations on early feeding of infants of HIV-1
      positive mothers in countries with deficient hygienic conditions is discussed.
      Even in exclusive breastfeeding, which is associated with a lower risk of HIV
      transmission than when supplements are given, the risk that the infant will
      acquire HIV-1 has to be balanced against the risk of formula feeding.
      Furthermore, it also has to be stressed that exclusive breastfeeding is a rarity
      in many poor countries. CONCLUSION: The dilemma of recommending appropriate early
      feeding to HIV-1-positive mothers will persist until further studies of the type
      performed by the Coutsoudis group in South Africa have been performed.

PMID- 14599054
TI  - Does circadian variation in risk factors for sudden infant death syndrome (SIDS)
      suggest there are two (or more) SIDS subtypes?
AB  - Sudden infant death syndrome (SIDS) is known to occur more frequently at night.
      In two studies it has now been shown that a prone sleep position is more strongly
      associated with SIDS occurring during the day, whereas night-time deaths are more
      strongly associated with maternal smoking and illness. CONCLUSION: This
      variation, although unexplained, does suggest at least two SIDS subtypes: one
      related to sleep position and possibly a thermal mechanism, and one related to an
      uncontrolled inflammatory response to infection predominantly occurring at night.
      In addition, there are probably other mechanisms that do not show a circadian
      variation.

PMID- 14599055
TI  - The size of the thymus: an important immunological diagnostic tool?
AB  - The report on the influence of seasonal factors on thymic size in early life
      describes a pattern of ultrasonographically measured thymic growth in Gambian
      infants including the finding of a smaller thymus in the hungry season. These
      factors raise a number of important questions: Is the size of the thymus relevant
      to its function and could measurement of the thymus be a useful immunological
      diagnostic tool in the investigation of thymic function in humans with a
      depressed immune system? CONCLUSION: Studies using the size of the thymus as an
      immunological diagnostic tool should be encouraged.

PMID- 14599056
TI  - Do we need another NSAID instead of indomethacin for treatment of ductus
      arteriosus in preterm infants?
AB  - Up until now indomethacin is the most extensively evaluated non-steroidal anti
      inflammatory drug (NSAID) in neonatal medicine. If used with due consideration to
      the physiologic role of prostaglandins, a 90 success rate can be reached and
      serious adverse drug effects prevented. CONCLUSION: The results reported by
      Bellander et al. support the idea that we do not need to study other substances
      of the same therapeutic class, with the same target--cyclooxygenase--in the
      prostaglandin cascade and with a similar pharmacological profile. Instead,
      indomethacin treatment regimes should be further improved with respect to their
      efficacy and safety.

PMID- 14599057
TI  - Identifying children at risk for language impairment: screening of communication
      at 18 months.
AB  - The difficulties of early identification of children at risk for language
      impairment are discussed against a background of other more or less important
      phenomena. CONCLUSION: Bruce et al.'s professional screening at 18 mo provides
      relevant information to detect children at risk for language impairment.

PMID- 14599058
TI  - Children and statins.
AB  - Use of statins is increasing among children with familial hypercholesterolaemia
      who previously have had to take unpalatable resins. In a selected group with no
      controls, children taking statins had similar scores for quality of life and
      anxiety as normative scores. The question that remains is how to improve dietary
      and disease information. CONCLUSION: Children with familial hypercholesterolaemia
      who are taking statins have no reduction in quality of life or increase in
      anxiety.

PMID- 14599059
TI  - Overnight central and peripheral temperature changes in normal infants.
AB  - AIM: To explore the relationship between central and peripheral temperature in
      normal infants after being put down to sleep. METHODS: Overnight shin and rectal
      temperatures of 21 normal infants were continuously recorded at home for three
      nights at 2 wk, 6 wk, 3 mo and 5 mo of age. Parents documented the start and end
      of feed/nappy changes during the night. RESULTS: An initial fall in rectal
      temperature was recorded on 149 out of 161 nights. This was linearly correlated
      with a rise in shin temperature for 106/149 (71%) nights (median R2 = 0.95, lower
      quartile 0.92, upper quartile 0.97). It was not possible to rule out a change in
      thermal insulation over the shins as a confounding variable in this strong
      association. However, a similar inverse relationship was seen between shin and
      rectal temperature during 111 of 121 (92%) feed/nappy changes. CONCLUSION: The
      fall in rectal temperature after being put down to sleep may be due to
      redistribution of heat rather than decreased production or heat loss. If causal,
      the development in early infancy of an inverse relationship between shin and
      rectal temperature may be important for cardiovascular homeostasis. Further sleep
      laboratory work is required to distinguish peripheral temperature changes on
      falling asleep from those associated with changes in thermal insulation.

PMID- 14599060
TI  - Circadian variations in sudden infant death syndrome: associations with maternal
      smoking, sleeping position and infections. The Nordic Epidemiological SIDS Study.
AB  - AIM: To study circadian variation in the sudden infant death syndrome (SIDS) and
      possible associations with risk factors for SIDS. METHODS: A questionnaire-based
      case-control study matched for place of birth, age and gender was conducted in
      Denmark, Norway and Sweden: The Nordic Epidemiological SIDS Study. The study
      comprised 244 SIDS victims and 869 control infants between September 1992 and
      August 1995. The main outcome was hour found dead. RESULTS: A significant
      circadian pattern was observed among the 242 SIDS victims with a known hour found
      dead, with a peak at 08.00-08.59 in the morning (n = 33). Of the SIDS victims,
      12% were found dead at 00.00-05.59, 58% at 06.00-11.59, 21% at 12.00-17.59 and
      9.0% at 18.00-23.59. When comparing night/morning SIDS and day/evening SIDS
      (found dead 00.00-11.59 and 12.00-23.59, respectively), the proportion of
      night/morning SIDS was high among infants of smoking mothers (81% vs 53%, p <
      0.001), infants with a reported cold (82% vs 64%, p = 0.007) and infants sleeping
      side/supine (81% vs 60%, p < 0.001). No associations were observed between hour
      found dead and other sociodemographic risk factors for SIDS. Risk (odds ratio and
      95% confidence interval) of night/morning SIDS and day/evening SIDS was 7.0 (4.5
      10.9) and 1.5 (0.8-2.5), respectively, for maternal smoking, 2.2 (1.5-3.1) and
      0.6 (0.3-1.3), respectively, if the infant had a reported cold, 3.7 (2.1-6.6) and
      3.1 (1.1-8.4), respectively, if the infant was put to sleep in the side position
      (supine reference), and 11.0 (5.9-20.2) and 21.6 (7.6-60.8), respectively, if the
      infant was put to sleep in the prone position. CONCLUSION: The observed higher
      proportion of night/morning cases in SIDS if the mother smoked, if the infant was
      reported to have a cold and if the infant was sleeping side/supine may contribute
      to the understanding of some epidemiological characteristics of SIDS.

PMID- 14599061
TI  - Birth season and environmental influences on patterns of thymic growth in rural
      Gambian infants.
AB  - AIM: In rural Gambia, birth season predicts infection-related adult mortality.
      Seasonal factors in early life may programme the immune system, possibly via an
      effect on thymic development. This study tested whether thymus size in rural
      Gambian infants is affected by birth season, defined as January-June (harvest,
      few infections) versus July-December (hungry, high infectious load). METHODS:
      Thymic volume (thymic index) was assessed sonographically at 1, 8, 24 and 52 wk
      in 138 singleton infants born over 14 consecutive months. Growth and morbidity
      were regularly assessed. RESULTS: Mean thymic index increased from 19.9 at 1 wk
      to 30.9 at 8 wk and 35.7 at 24 wk, then fell to 32.0 at 52 wk. Thymic index was
      associated with each preceding thymic index up to 24 wk. This tracking persisted
      after correcting for infant weight and month of measurement (p < 0.01). Thymic
      index at 1 wk was marginally but non-significantly lower in hungry season births
      (p = 0.06). Thymic index was lower in hungry season measurements; this effect
      persisted after adjusting for current weight and infection markers, and was
      strongest at 8 wk (p = 0.001). CONCLUSION: These results describe a pattern of
      thymic growth followed by diminution in size. An infant's thymic index tracks
      despite changes in body weight and season. Thymic index was lower in the hungry
      season. This appears not to be explained by infection or nutritional status. A
      possible influence of trophic factors in breast milk merits investigation.

PMID- 14599062
TI  - Oesophageal pH monitoring in children: how is it perceived by the parents and
      does the technique change feeding and daily activity?
AB  - AIM: To determine whether oesophageal pH monitoring in infants induces changes in
      daily activity and feeding, and with the help of a questionnaire to evaluate how
      parents perceive pH monitoring. METHODS: The parents of 100 children,
      consecutively referred for oesophageal pH monitoring, were asked by one of the
      authors (A.A.) to respond to a standardized questionnaire immediately after the
      end of the procedure. Twenty questions were asked, concerning five topics:
      feeding (4 questions), activity (6 questions), perception of the parents (6
      questions), accuracy of the provided information (3 questions), and previous
      experience with oesophageal pH-metry (1 question). For statistical analysis,
      every variable was qualified as "no change" and "change" for feeding and
      activity, as "positive" or "negative" regarding the perception of the test, and
      as "sufficient" or "insufficient" regarding the information provided. The answers
      to the questions were also analysed according to the result of the oesophageal pH
      monitoring (normal vs abnormal), and according to whether or not there was
      previous experience of oesophageal pH-metry in a first degree relative. RESULTS:
      Changes in feeding occurred in 28% of cases and changes in activity in 30%, but
      did not differ according to the oesophageal pH-metry result. Equally, the
      perception of the parents regarding the test (37% negative), the acceptability of
      a second pH-metry test (refusal in 52%) and previous experience with oesophageal
      pH-metry (positive in 25%) were not influenced by the result of the pH
      monitoring. Parents of infants with abnormal oesophageal pH monitoring were more
      frequently dissatisfied with the information about the nature of the test
      provided before the test and also the results than parents of infants with normal
      results (52% vs 19%, respectively; p < 0.05). CONCLUSION: According to the
      perception of the parents, pH monitoring induces changes in feeding and activity
      in 28% and 30%%, respectively; 63% of the parents considered pH monitoring to be
      well tolerated. Parents of infants with abnormal pH monitoring results need more
      attention.

PMID- 14599063
TI  - Urinary 8-hydroxydeoxyguanosine excretion in children before and after therapy
      for eradication of Helicobacter pylori infection.
AB  - AIM: A number of reports have implicated oxygen free radicals in the pathogenesis
      of Helicobacter pylori (H. pylori)-associated disease. 8-hydroxydeoxyguanosine (8
      OHdG) has recently been accepted as a sensitive marker for reflecting the
      oxidative DNA damage. However, there have been no previous studies comparing the
      changes in urinary 8-OHdG excretions before and after therapy for eradication of
      H. pylori infection, or to examine 8-OHdG excretions in children with H. pylori
      infection. The aim of this study was therefore to examine the DNA damage in
      gastric mucosal cells in children with H. pylori infection. METHODS: Urinary 8
      OHdG excretions were measured before and after therapy for eradication of H.
      pylori infection in 15 children diagnosed with the H. pylori infection and 13
      parents who were also suffering from the same infection. RESULTS: In both the
      children and their parents, no significant differences were found in urinary 8
      OHdG excretions either before or after the eradication therapy. Furthermore,
      there was no significant difference in urinary 8-OHdG excretions between 8
      children with peptic ulcers and 7 children without ulcers, either before or after
      the therapy. CONCLUSION: These results suggest that measurement of urinary 8-OHdG
      levels is not useful for evaluation of the DNA damage in H. pylori-infected
      gastric mucosa in children.

PMID- 14599064
TI  - Pubertal growth and development in cystic fibrosis: a retrospective review.
AB  - AIM: Normal growth patterns are seen throughout the first decade in children with
      cystic fibrosis (CF). Growth in the second decade is, however, less satisfactory
      and may reflect pubertal delay. This study was performed to assess the extent of
      pubertal delay, to examine factors that influence the timing and magnitude of the
      pubertal growth spurt, and to establish whether the final height for most CF
      patients differed significantly from the normal population. METHODS: Thirty
      subjects (16 male) attending a single centre were studied. Peak height velocity
      (PHV), final height and ages when achieved were compared with population norms.
      Outcome data were correlated with disease severity using Shwachman and Chrispin
      Norman scores and forced expiratory volume in 1 s. RESULTS: PHV was significantly
      later in both genders in this CF population compared with Tanner and Whitehouse
      standards: boys 14.6 y (95% confidence interval (95% CI) 12.4-16.8, p < 0.01) and
      girls 12.6 y (95% CI 10.5-14.7, p < 0.01). Mean PHV was also lower in both
      genders (boys 7.7 cm y(-1) and girls 6.4 cm y(-1), both p<0.001). However, final
      heights did not differ significantly from Freeman standards (height standard
      deviation scores: males--1.2, females--0.1); 52% of final heights equalled or
      exceeded the mid-parental centile. CONCLUSION: CF patients showed suboptimal PHVs
      with a later pubertal growth spurt influenced by disease severity, but eventually
      achieved a normal final height.

PMID- 14599065
TI  - Improved final height in Turner's syndrome following growth-promoting treatment
      at a single centre.
AB  - AIMS: To examine the final height (FH) outcome of girls with Turner's syndrome
      (TS) treated at a single Scottish centre (Glasgow group), to compare it with an
      earlier national analysis (Scottish group) and to suggest reasons for any change.
      METHODS: Retrospective growth and treatment data for 29 Glasgow patients were
      compared with those of 26 Scottish patients. RESULTS: Age at GH start (mean +/-
      SD) was 10.1 +/- 2.6 vs 12.1 +/- 1.7 y (p < 0.01) in the Glasgow versus Scottish
      groups, with overall duration of treatment 6.2 +/- 2.4 vs 3.7 +/- 1.1 y (p <
      0.001) and years of GH treatment before pubertal induction 2.7 +/- 2.8 vs 0.3 +/-
      0.8 y (p < 0.001), respectively. Pubertal induction was at a similar age: 12.7 +/
      1.8 vs 12.8 +/- 1.8 y (ns). FH was 151.1 +/- 4.6 cm in the Glasgow group
      compared with 142.6 +/- 5.6 cm in the Scottish group (p < 0.001), with FH -
      projected adult height (PAH) 5.7 +/- 4.6 cm vs 0.6 +/- 3.6 cm (p < 0.001),
      respectively. Univariate analysis of the Glasgow group's FH - PAH with a number
      of growth and treatment variables identified no statistically significant
      relationships. CONCLUSION: This group's improved FH and FH - PAH, relative to an
      earlier sample, are attributed to the introduction of GH treatment from a younger
      age and for longer, overall and before pubertal induction. In addition, the
      authors believe that compliance with treatment has been enhanced by this single
      centre's dedicated Turner clinic and the efforts of its established "growth
      team". These data demonstrate that a favourable FH can be achieved using a safe
      and financially viable dose of GH, while inducing puberty at a "normal" age.

PMID- 14599066
TI  - Longitudinal growth and height velocity of Japanese children with Down's
      syndrome.
AB  - AIM: To determine the natural growth pattern of Japanese children with Down's
      syndrome. METHODS: Longitudinal height data of 85 patients (43 males, 42 females)
      from birth to final height were analyzed. Based on these data, semi-longitudinal
      standard growth curves and height velocity curves for Down's syndrome were drawn.
      RESULTS: The means +/- SD of final height of males and females with Down's
      syndrome were 153.2 +/- 5.6 and 141.9 +/- 4.2 cm, respectively. They were -3.0 SD
      and -2.8 SD for Japanese standards. Mean peak height velocities were 8.9 and 7.5
      cm y(-1), and the ages at peak height velocity were 11.6 and 10.2 y for males and
      females, respectively. CONCLUSION: The mean height of patients with Down's
      syndrome was around -2 SD for normal children before puberty. Their pubertal
      growth spurt starts about 1 y earlier and their peak height velocity was about
      1.3-1.4 cm shorter than for normal children.

PMID- 14599067
TI  - Influence of dietary intervention on growth in children with
      hypercholesterolaemia.
AB  - AIM: To determine whether a moderately reduced fat diet affects longitudinal
      growth in children with hypercholesterolaemia with a mean duration of 7.42 +/-
      1.93 y. METHODS: Subjects with hypercholesterolaemia, total cholesterol above
      5.18 mmol/L and LDL-cholesterol above 3.49 mmol/L (n = 144; 69 males and 75
      females) from 2 to 13 y of age were studied. Patients were seen in our outpatient
      department for regular health check-ups. Weight and height were measured every
      year. At the same time, cholesterol, triglycerides, LDL-C, HDL-C, A-apoprotein
      and B-apoprotein levels were analysed. Furthermore, degrees of compliance at 1
      mo, 6 mo and each year after starting the dietary treatment were determined.
      RESULTS: No significant change in height or weight was found after fat
      restriction. In contrast, significant reductions in total cholesterol, LDL
      cholesterol and B-apoprotein levels of 19%, 24% and 14%, respectively, were
      detected. Finally, no significant differences were seen in HDL-cholesterol, A
      apoprotein or triglycerides. CONCLUSIONS: These data support the hypothesis that
      growth is not influenced by moderate fat restriction in healthy children who
      otherwise have normal nutrition.

PMID- 14599068
TI  - Chediak-Higashi syndrome: four cases from Northern Finland.
AB  - Chediak-Higashi syndrome (CHS) is a rare multiorgan disease entity with autosomal
      recessive inheritance characterized by oculocutaneous albinism, bleeding
      tendency, recurrent bacterial infections and various neurological symptoms.
      Intracellular vesicle formation is deficient, resulting in giant granules in many
      cells, e.g. giant melanosomes in the melanocytes. Diagnosis has been based on
      morphological examination of peripheral blood and bone marrow, with giant
      granules seen in cells of the myeloid lineage and in lymphocytes. The ultimate
      diagnostic test is to look for a mutated LYST gene. Most patients develop an
      accelerated phase of the disease with deposition of lymphohistiocytes in the
      liver, spleen, lymph nodes and bone marrow, resulting in hepatosplenomegaly, bone
      marrow infiltration and haemophagocytosis. Peripheral blood neutropenia becomes
      more profound as anaemia and thrombocytopenia develop. Most patients succumb
      before the age of 10 years. Four patients with CHS are described, one of whom is
      a long-term survivor after successful allogeneic bone marrow transplantation, two
      succumbed during the accelerated phase and one is living with a chronic form of
      the disease. CONCLUSION: Allogeneic bone marrow transplantation from an HLA
      matched sibling is the therapy of choice and should be performed early. If there
      is no matched family donor, an unrelated donor or a placental blood graft is a
      good alternative. The clinical picture of CHS is heterogeneous and therapeutic
      decisions need to be made on an individual basis.

PMID- 14599070
TI  - Supraventricular tachycardia: an incidental diagnosis in infants and difficult to
      prove in children.
AB  - AIMS: To determine (a) the age distribution at first clinical supraventricular
      tachycardia (SVT) presentation; (b) the time interval between first clinical
      suspicion and electrocardiographic proof of SVT; c) the most indicative symptoms
      and signs of SVT; and (d) the SVT mechanism and its age distribution according to
      surface ECG. METHODS: The records of 55 children (32 males and 23 females) with
      electrocardiographically proven SVT but without congenital heart disease were
      reviewed. RESULTS: At diagnosis, 27 patients (49%) were younger than 1 y
      (infants), and 28 (51%) were older than 1 y (children). Only a quarter of infants
      presented with symptoms. The majority (20/27), however, were detected during
      routine investigation without having any complaints. Children presented with
      symptoms (mostly palpitations) in almost 90% of cases. Despite these symptoms,
      the median time interval between first clinical presentation suggestive of SVT
      and electrocardiographic proof of SVT was 138 d. Using surface ECG, we were
      unable to show any age-dependency of the SVT mechanism in our study group.
      CONCLUSION: In infants SVT is a chance finding; SVT can only be proven
      electrocardiographically with a median delay of 138 d, despite the presence of
      symptoms; SVT using a (concealed) accessory pathway is the most common mechanism.

PMID- 14599069
TI  - Glomerular filtration rate: measure creatinine and height rather than cystatin C!
AB  - AIM: Inulin clearance (Cin) is the gold standard for assessing glomerular
      filtration rate (GFR). Other methods are based on the plasma creatinine
      concentration (Pcreat), creatinine clearance (Ccreat), the Haycock-Schwartz
      formula and the plasma concentration of cystatin C (PcysC), a 13 kDa basic
      protein produced at a constant rate by all nucleated cells. The present
      prospective study was thus designed to evaluate the reliability of PcysC as a
      marker of GFR in comparison with that of Pcreat, Ccreat and the Haycock-Schwartz
      formula, using Cin as the gold standard. METHODS: Ninety-nine children (51 m/48
      f), with a median age of 8.3 y (1.0-17.9) were studied. Using a cut-off for Cin
      of 100 ml/min per 1.73 m2, 54 children (54.5%) had impaired GFR. Those with
      normal GFR were comparable for age, height, weight and body mass index. RESULTS:
      Logistic regression, ROC analysis and linear regression all showed that Ccreat
      was the best parameter to discriminate between impaired and normal GFR, followed
      by the Haycock-Schwartz formula, PcysC, and finally Pcreat, each one being
      significantly more predictive than the next. CONCLUSION: GFR is better assessed
      by the Haycock-Schwartz formula than by PcysC or Pcreat alone. It is therefore
      concluded that when urine collection is not possible, simply measuring the
      child's Pcreat and height is the best, easiest and cheapest way to assess GFR.

PMID- 14599071
TI  - Diaphragm dimensions of the healthy term infant.
AB  - AIM: Human neonatal diaphragm development has not been extensively studied.
      Previous work in children and adults suggests that diaphragm thickness (t(di)) is
      in scale with body size such that maximal transdiaphragmatic pressure (P(dimax))
      remains relatively constant. Such assessments have not been made in healthy term
      infants. This study was designed to evaluate the relationships among t(di), body
      dimensions and P(dimax) in healthy term infants. METHODS: It was hypothesized
      that in healthy term infants 1) t(di) is positively correlated with body size and
      2) calculated P(dimax) is independent of body weight and length. Fifteen
      clinically stable term infants (8 males and 7 females) were recruited
      [birthweight (BW), 3.3 +/- 0.7 kg, (mean +/- SD); head circumference (HC), 33.7
      +/- 2 cm; body length (BL) 50 +/- 3 cm; gestational age (GA) 39 +/- 1 wk; and
      postnatal age 1.7 +/- 0.8 day]. Ultrasound was used to visualize the diaphragm at
      the level of the zone of apposition and measure t(di). Standard techniques were
      used to measure the anthropometric dimensions of the rib cage. P(dimax) was
      calculated using the piston-in-cylinder model of diaphragm function. RESULTS:
      Significant correlations were found among t(di) and BW (R = 0.58), BL (R = 0.58)
      and HC (R = 0.65) but not between GA (R = 0.20). Larger infants tended to have
      thicker diaphragms and larger cross-sectional areas of the lower rib cage
      (A(ZAP)). For the group, calculated P(dimax) was independent of either body
      weight or length and was greater than that calculated for adults. CONCLUSION: It
      is concluded that diaphragm mass in healthy term infants is proportional to body
      size, whereas calcuated P(dimax) is independent of body size. Since calculated
      P(dimax) is greater than that predicted for adults, there may be perinatal
      diaphragm strengthening. This may assist the infant in generating sufficient
      pressure to overcome the enormous elastic and resistive loads imposed during
      perinatal pulmonary transition.

PMID- 14599072
TI  - Haemodynamic features during high-frequency oscillatory ventilation in preterms.
AB  - AIM: To compare the haemodynamic status during high-frequency oscillatory
      ventilation and conventional mechanical ventilation in very preterm infants with
      respiratory distress syndrome. METHODS: Thirty-two neonates of less than 30 wk
      gestation randomly assigned to high-frequency oscillatory ventilation (n = 15) or
      conventional mechanical ventilation (n = 17) had three echocardiographies and one
      cerebral Doppler-echography under the same ventilation during the first 48 h of
      life. RESULTS: Mean airway pressure was 2 cm H2O higher in infants ventilated
      with high-frequency oscillatory ventilation at the different echocardiographies.
      Comparable right ventricular indexes were observed in the two groups. Reduction
      of the ductus arteriosus diameter and ductal closure were significant only in
      neonates ventilated conventionally. Left ventricular performance and left
      ventricular contractility did not differ between the groups. The high-frequency
      group had lower end diastolic velocity and a higher resistance index in the
      anterior cerebral artery. CONCLUSION: Compared with conventional mechanical
      ventilation, high-frequency oscillatory ventilation was achieved without altering
      cardiac function. However, the inability of the left ventricle to improve its
      performance in the presence of a significant ductal shunt suggests a narrow range
      of optimal pressures under this ventilatory mode.

PMID- 14599073
TI  - Tolerance to early human milk feeding is not compromised by indomethacin in
      preterm infants with persistent ductus arteriosus.
AB  - AIM: Early human milk feeding is beneficial for gut and brain development.
      Persistent ductus arteriosus (PDA) and indomethacin may compromise enteral
      function in preterm infants. For many years enteral milk feedings have continued
      in preterm infants receiving indomethacin for PDA. The aim of this study was to
      investigate whether this strategy is efficient in terms of risks and tolerance to
      early enteral feeding. METHODS: This retrospective study included 64 inborn
      infants of <29 wk gestational age (GA), 32 infants who received indomethacin for
      symptomatic PDA (case infants) and 32 matched controls. Case infants had a mean
      (SD) GA of 26.3 wk (1.3) and body weight 839 g (203) versus controls GA 26.4 wk
      (1.2) and body weight 896 g (213) (p = 0.82 and 0.27, respectively). Case infants
      had higher respiratory morbidity; 90.6% versus 50% of controls needed mechanical
      ventilation (p = 0.000). RESULTS: Case infants received human milk from a median
      (range) age of 4.0 h (1.5-27.5), and controls from 5.3 h (2.0-38.0) (p = 0.092).
      The first dose of indomethacin was given at a mean age of 1.7 d (1.0). There were
      no differences between the two groups in feeding volumes or gastric residuals on
      days 1 to 7. Mean (SD) feeding volume on day 7 was 64 ml/kg (31) in case infants
      and 76 ml/kg (30) in controls (p = 0.23). Four infants developed necrotizing
      enterocolitis: two case infants and two controls (p = 1.00). CONCLUSION: Early
      enteral feeding with human milk, starting within the first hours of life, seems
      to be as well tolerated in preterm infants treated with indomethacin for PDA as
      in their matched controls.

PMID- 14599074
TI  - Postnatal adaptation of cerebral blood flow using near infrared spectroscopy in
      extremely preterm infants undergoing high-frequency oscillatory ventilation.
AB  - AIM: To determine cerebral blood flow using near infrared spectroscopy in
      extremely preterm infants undergoing high-frequency oscillatory ventilation
      during the first three days of life. Low cerebral blood flow has been associated
      with both intra-ventricular haemorrhage and periventricular leucomalacia. It is
      well established that cerebral blood flow increases over the first three days of
      life in extremely preterm infants who are conventionally ventilated with
      intermittent positive pressure ventilation. However, there is no information
      about cerebral blood flow in preterm babies undergoing high-frequency oscillatory
      ventilation. In addition, there are concerns that high-frequency oscillatory
      ventilation may be associated with an increased incidence of intra-ventricular
      haemorrhage in premature infants. METHODS: Thirteen appropriately grown, preterm
      infants of less than 28 wk gestation who were admitted to the neonatal unit at
      University College Hospital, London were studied using near infrared
      spectroscopy. Left ventricular output and right ventricular output were assessed
      echocardiographically. RESULTS: Extremely preterm infants undergoing high
      frequency oscillatory ventilation have remarkably low cerebral blood flow in the
      first 12 h of life, median 6.7 (range 4.4-11) mls. 100 g(-1) min(-1) followed by
      an increase over the subsequent three days. Left ventricular output also
      increased over the first three days of life, whereas right ventricular output
      showed no clear relationship with time. Despite low cerebral blood flow only one
      infant had evidence of major cerebral injury. CONCLUSION: Cerebral blood flow is
      extremely low in this group of preterm babies. Despite this extremely low
      cerebral blood flow, the clinical outcome is good. There was an increase in
      cerebral blood flow and a corresponding increase in left ventricular output over
      the first few days of life.

PMID- 14599075
TI  - Neonatal hypotonia: don't forget the Prader-Willi syndrome.
AB  - During the neonatal period the diagnosis of the Prader-Willi syndrome (PWS) is
      difficult because the syndrome is expressed mainly by severe hypotonia at this
      age and the typical clinical features of later life are not yet present. AIM: To
      identify all the PWS clinical markers in severe hypotonic newborns, which could
      facilitate an early diagnosis of the syndrome. METHODS: Twenty-one PWS newborns
      (14 males and 7 females) with severe hypotonia at birth were evaluated.
      Paediatricians skilled in syndromology carried out a careful clinical
      examination. Fluorescent in situ hybridization (FISH) analysis and/or a
      methylation test was used to confirm the PWS clinical diagnosis. RESULTS: The
      clinical diagnosis of PWS was reached at a mean age of 7.4 mo with genetic
      confirmation at 11 mo of life. In 12 newborns at least 3 craniofacial features
      were present (57%), suggesting the diagnosis of PWS. Two craniofacial dysmorphic
      characteristics were described in 6 newborns and only 1 in 3 cases.
      Cryptorchidism was monolateral in 6 and bilateral in 7 patients; in one newborn
      both testes were in scrotum. A micropenis was described in one patient and
      hypoplasia of the labia minora was reported in two females. CONCLUSIONS:
      Diagnosis by means of dysmorphologic evaluation is difficult in the neonatal
      period. The presence of severe hypotonia should always induce neonatologists to
      perform specific genetic tests in order to obtain an early diagnosis of PWS.

PMID- 14599076
TI  - Identifying children at risk for language impairment: screening of communication
      at 18 months.
AB  - AIM: To investigate the possibility of identifying children at risk for language
      impairment based on a new screening instrument to assess communication and
      language skills at 18 mo of age. METHODS: At 18 mo, 58 children were assessed
      with a screening instrument for communication and language consisting of a
      professional assessment and a parents' questionnaire. Students of speech and
      language pathology, well trained in child language assessment, carried out the
      professional assessment, which was based on observations of play behaviour,
      interaction and expressive and receptive language skills. Of the 58 children, 43
      attended a follow-up assessment of language skills at 54 mo of age. RESULTS: Nine
      children were considered to be at risk for language impairment at 18 mo and 10
      children were evaluated as being at risk at 54 mo. A significant positive
      correlation was found between the professional evaluations at 18 mo and the
      language tests at 54 mo. Verbal comprehension and pretend play correlated
      significantly with the results on the language tests. CONCLUSION: A professional
      screening of communication and language at 18 mo of age is worthwhile for
      predicting problems in language development. The results further show that
      language comprehension and pretend play rather than expressive skills should be
      emphasized.

PMID- 14599077
TI  - Quality of life, anxiety and concerns among statin-treated children with familial
      hypercholesterolaemia and their parents.
AB  - AIM: To assess the quality of life, anxiety and concerns among statin-treated
      children with familial hypercholesterolaemia (FH) and their parents. METHODS: 69
      FH children on statin therapy and 87 parents (51 families) participated in this
      study. Quality of life of the children, and anxiety levels of both the children
      and their parents, were investigated using self-report questionnaires. In
      addition, a questionnaire was designed to evaluate FH-specific concerns of these
      children and their parents on six different topics: 1, knowledge about FH; 2,
      experience of the disease; 3, family communication; 4, screening; 5, diet; and 6,
      experience of medication therapy. RESULTS: FH children and their parents reported
      no problems with regard to quality of life and anxiety. In contrast, the FH
      survey showed specific FH-related concerns. One-third of the children thought
      that FH can be cured, and 44% of the children suffered from the fact they have
      FH, but taking medication makes them feel safer (62%). The majority of the
      children kept a low cholesterol diet and more than 50% took care not to eat too
      much fat. Almost 38% of the parents experienced FH as a burden to their family
      and 79% suffered because their child had FH. CONCLUSION: These findings show that
      statin-treated children with FH and their parents did not report affected
      psychosocial functioning, but did show specific FH-related concerns.

PMID- 14599079
TI  - Pinpoint skin lesions in a familial hypercholesterolaemia homozygote.
AB  - The case is reported of a 2-y-old girl referred to the outpatient lipid clinic
      because of a tiny cutaneous xanthoma on the dorsum of the left foot and a family
      history of hyperlipidaemia and coronary heart disease (CHD). Fasting serum total
      cholesterol levels were remarkably high (27.1 mmol l(-1), 1050 mg dl(-1)) and DNA
      analysis confirmed homozygous familial hypercholesterolaemia (class II mutation).
      Serum lipids were not affected by dietary intervention and cholestyramine
      treatment, so low-density lipoprotein apheresis was scheduled to commence at the
      age of 4 y. CONCLUSION: An early lipid profile determination should be performed
      in children with a family history of premature CHD, since the physical
      examination may be unremarkable even in cases of severe hyperlipidaemia during
      the first years of life.

PMID- 14599078
TI  - Pregnancy and childbirth-related factors associated with recurrent antibiotic use
      in infants.
AB  - AIM: To determine the reasons for the possible overuse of antibiotics by
      investigating whether family-related medical, behavioural, emotional, and social
      risk factors during the mother's pregnancy and childbirth are associated with
      subsequent recurrent antibiotic therapy of infants. METHODS: Subject selection
      was based on stratified randomized cluster sampling. A total of 1443 women (91%)
      and their spouses expecting their first child gave informed consent to
      participate and 1287 infants were born. The parents of 817/1025 infants (80%)
      reported the number of courses of antibiotic therapy the child had received at
      the ages of 9 and 18 mo. The outcome measure was the number of courses of
      antibiotic therapy (none/1-5/=6) given during the first 18 mo of life. The
      explanatory variables included family-related factors during the pregnancy and
      immediately after childbirth. RESULTS: In the final multivariate stepwise
      analysis, parents' long-term illnesses were associated with recurrent antibiotic
      medication. CONCLUSIONS: Parents with long-term illnesses need special guidance
      and support from the beginning of the mother's pregnancy in order to minimize the
      subsequent risk for recurrent antibiotic therapy of their infants. Preventive
      healthcare workers should be aware of the effects of these factors on parental
      guidance.

PMID- 14599080
TI  - Growth failure and diabetes in cystic fibrosis: have you considered Turner
      syndrome?

PMID- 14599081
TI  - Severe venous thrombosis in an infant heterozygous for the G20210A mutation in
      the prothrombin gene.

PMID- 14599082
TI  - Cancer therapies crisis in the USA.

PMID- 14599083
TI  - Irinotecan (Campto) in the treatment of pancreatic cancer.
AB  - Irinotecan (Campto) is a topoisomerase I inhibitor currently approved for the
      treatment of metastatic colon cancer. Single-agent irinotecan has also
      demonstrated modest activity in a number of other advanced solid tumors,
      including lung, gastric and pancreatic cancer. Preclinical data suggest a
      potentially additive and/or synergistic interaction between irinotecan and
      gemcitabine (Gemzar). This combination has demonstrated improved response rates
      in patients with pancreatic cancer. Unfortunately, a recently reported Phase III
      trial of gemcitabine with or without irinotecan revealed no survival benefit for
      the combination. Future combinations of irinotecan continue to be explored in an
      effort to further improve the treatment of this relatively chemorefractory
      disease. Thus far, no single agent or combination has been shown to be superior
      to gemcitabine alone as palliative therapy for advanced/metastatic pancreatic
      cancer. A promising combination of irinotecan with oxaliplatin (Eloxatin) and
      fluorouracil will be assessed in a Phase III study.

PMID- 14599084
TI  - Molecular neuro-oncology and development of targeted therapeutic strategies for
      brain tumors. Part 1: Growth factor and Ras signaling pathways.
AB  - Brain tumors are a diverse group of malignancies that remain refractory to
      conventional treatment approaches, including radiotherapy and cytotoxic
      chemotherapy. Molecular neuro-oncology has now begun to clarify the transformed
      phenotype of brain tumors and identify oncogenic pathways that may be amenable to
      targeted therapy. Growth factor signaling pathways are often upregulated in brain
      tumors and may contribute to oncogenesis through autocrine and paracrine
      mechanisms. Excessive growth factor receptor stimulation can also lead to
      overactivity of the Ras signaling pathway, which is frequently aberrant in brain
      tumors. Receptor tyrosine kinase inhibitors, antireceptor monoclonal antibodies
      and antisense oligonucleotides are targeted approaches under investigation as
      methods to regulate aberrant growth factor signaling pathways in brain tumors.
      Several receptor tyrosine kinase inhibitors, including imatinib mesylate
      (Gleevec), gefitinib (Iressa) and erlotinib (Tarceva), have entered clinical
      trials for high-grade glioma patients. Farnesyl transferase inhibitors, such as
      tipifarnib (Zarnestra), which impair processing of proRas and inhibit the Ras
      signaling pathway, have also entered clinical trials for patients with malignant
      gliomas. Further development of targeted therapies and evaluation of these new
      agents in clinical trials will be needed to improve survival and quality of life
      of patients with brain tumors.

PMID- 14599085
TI  - Medulloblastomas: do molecular and biologic markers indicate different prognoses
      and treatments?
AB  - The origin and histological classification of embryonal tumors, which make up the
      largest group of malignant pediatric brain malignancies, are two controversial
      issues. However, in recent years, progress has been made in our understanding of
      the molecular genetic abnormalities that govern their onset and/or progression.
      Several of these abnormalities appear to involve alterations in the signaling
      system controlling normal cerebellar development. An improved understanding of
      both the biology and clinical relevance of these molecular defects is probably
      the only means by which neuro-oncologists will improve the management of these
      tumors, thus reducing disease- and treatment-related morbidity and mortality.

PMID- 14599086
TI  - Role of resection for newly diagnosed malignant gliomas.
AB  - The surgical neuro-oncology literature testifies to the longstanding argument
      about the benefits (or lack thereof) of aggressive debulking of high-grade
      gliomas. Publications from the last decade addressing this question will be
      reviewed. The absence of randomized clinical trials and paucity of prospectively
      collected information continue to leave this issue unresolved, although most
      evidence continues to support a modest benefit of debulking over biopsy.

PMID- 14599087
TI  - Update on the treatment of neuroendocrine tumors.
AB  - Neuroendocrine tumors represent a group of neoplasias characterized by
      significant histopathological and biological heterogeneity. The basic study of
      the biological features of neuroendocrine tumors should allow the oncologist to
      identify those tumor subsets more sensitive to a particular medical treatment.
      For example, in metastatic or advanced disease, locoregional treatments, as well
      as radionuclide therapies, should be suggested only in selected cases. Although
      it has no significant effect on tumor growth, biotherapy with somatostatin
      analogs and/or interferon-alpha is recommended for either well-differentiated or
      functioning tumors. On the other hand, chemotherapy is effective in the treatment
      of those tumors characterized by a poor differentiation grade and a high
      proliferation rate. Novel therapies, new pharmacological formulations and more
      selective somatostatin analogs are now under clinical investigation for the
      treatment of neuroendocrine tumors.

PMID- 14599088
TI  - Recommendations for the management of malignant gliomas in the elderly.
AB  - According to epidemiological estimations, the elderly are going to constitute an
      increasing proportion of patients with gliomas in the near future. Predominantly
      glioblastoma histology with invariably fatal outcome, disabling comorbidities and
      presumed low tolerability of radiochemotherapeutic treatments are the main
      reasons why elderly patients have been under-represented in the majority of neuro
      oncological clinical trials conducted so far. Some small retrospective studies
      have reported that patients with good performance status receiving surgery plus
      radiotherapy, and sometimes chemotherapy, may achieve a survival comparable with
      that of younger patients, however, in the absence of randomized studies, the
      balance of benefits and adverse effects of aggressive treatments remains
      controversial. Multidisciplinary evaluation of prognostic factors, such as
      performance status, cognitive functions, tumor operability and burden of
      comorbidities, appears to be mandatory in order to choose which patients must not
      be deprived of an integrated treatment with surgery, full-dose radiotherapy and
      chemotherapy, and which patients may reasonably be given a shorter radiotherapy
      plan, or even no treatment at all due to the rapidly fatal course of their
      disease. Peculiar features of malignant gliomas in the elderly and some practical
      recommendations of management will be presented and discussed in this review.

PMID- 14599089
TI  - Update on the therapeutic approaches to brain tumors.
AB  - Neuro-oncology is a rapidly growing field of study. The understanding of brain
      tumors has expanded in pace with advances in the field of molecular biology and
      genetics. Diagnoses are more accurate, biopsy and surgical intervention safer,
      radiotherapy more focused and chemotherapy safer and better tolerated. Novel
      strategies based on the understanding of brain tumor biology are emerging as
      targeted approaches to therapy. Despite all this, only a minority of patients
      with certain subsets of brain tumors have experienced prolonged survival. This
      review focuses on the standard and emerging therapies for the two most common
      categories of brain tumors: gliomas and meningiomas. Primary CNS lymphoma, while
      a relatively rare tumor, is also included as a topic of discussion as the
      achievements in its treatment represent the principal strides in the evolution of
      neuro-oncology.

PMID- 14599090
TI  - Sentinel lymph node biopsy for melanoma of the head and neck.
AB  - Since its first description nearly two centuries ago, melanoma has been a
      difficult disease to diagnose and treat. With the incidence and mortality rates
      slowly increasing, understanding this disease is more important than ever.
      Herein, the current diagnostic and treatment recommendations for melanoma of the
      head and neck are reviewed, with special emphasis on the use of sentinel lymph
      node biopsy (SLNB). For the past decade, SLNB has been a well-accepted procedure
      in the treatment of truncal and extremity melanoma, providing useful information
      for both treatment and prognosis. Still, despite its clear role in the rest of
      the body, the role of SLNB has not yet been fully defined in the management of
      melanoma of the head and neck. The complexity of lymphatic drainage patterns and
      the frequent need to remove sentinel lymph nodes from the parotid gland, thus
      placing the facial nerve at risk, have made head and neck surgical oncologists
      slow to adopt this method. However, current data from several trials indicate
      that in the head and neck, sentinel lymph nodes can be identified reliably
      approximately 98% of the time using intraoperative lymphatic mapping. In
      addition, the false-negative and complication rates are appropriately low. SLNB
      allows for accurate staging of patients, informed discussions of prognosis and
      the use of adjuvant therapies, including radiation and interferon-alpha2b. For
      these reasons, the authors believe that SLNB will become the standard-of-care for
      head and neck melanoma as well as for other body sites.

PMID- 14599091
TI  - Active specific immunotherapy for colorectal cancer.
AB  - With advances in molecular biology and the identification of tumor-associated
      antigens, a number of new strategies have been developed in an attempt to
      overcome the limits of chemotherapy and to aid in the fight to cure patients of
      metastatic and micrometastatic colorectal carcinomas. Biological therapy has now
      moved into the era of immunotherapy. Nonspecific immunotherapy has been surpassed
      by modalities that produce a specific and potent immune response against
      identifiable tumor-associated antigens, so called active specific immunotherapy.
      Approaches that come under this heading include tumor cell vaccines, anti
      idiotypic antibody therapy and dendritic cell vaccines. Cells can be further
      boosted by the use of immunostimulatory cytokines. This review aims to evaluate
      current strategies of immunotherapy for colorectal cancer with particular
      emphasis on the clinical aspects.

PMID- 14599092
TI  - Epidemiology and clinical burden of acute myeloid leukemia.
AB  - Acute myeloid leukemia is the most common type of leukemia in adults, yet it
      continues to have the lowest survival rate of all leukemias. Prognosis for the
      elderly in particular continues to be dismal. This review examines the currently
      available literature on the epidemiology, etiology, diagnosis and management of
      acute myeloid leukemia. New therapies and therapeutic strategies must be found to
      improve survival, especially as the worldwide population ages. Gemtuzumab
      ozogamicin (Mylotarg) for the treatment of patients with CD33-positive acute
      myeloid leukemia, selective FLT3 inhibitors currently in advanced development
      (e.g., SU11248, PKC412, CT53518 and CEP-710) and other targeted compounds (e.g.,
      farnesyl transferase inhibitors, BCL-2 inhibitors and interleukin-2) may present
      initial opportunities to achieve improved outcomes.

PMID- 14599093
TI  - Progress in the medical treatment of advanced colorectal cancer.
AB  - Despite recent progress made in screening, prevention and adjuvant treatment of
      colorectal cancer, a large proportion of patients with this disease develop local
      recurrences or distant metastases. The management of these patients requires a
      multidisciplinary approach. Surgery must be performed whenever possible for
      metastases confined to the liver or lung. However, in most cases, chemotherapy
      and supportive care are the only feasible treatments. This review describes the
      research carried out in this field through randomized trials and meta-analyses
      aimed at optimizing the efficacy of front-line chemotherapy.

PMID- 14599094
TI  - Pyrimidine nucleoside analogs in cancer treatment.
AB  - Pyrimidine nucleoside analogs are essential components of hematological
      malignancy therapy and are also used in the treatment of solid tumors. These
      agents act as antimetabolites, compete with physiologic pyrimidine nucleosides
      and, consequently, interact with a large number of intracellular targets to
      induce cytotoxicity. Pyrimidine nucleoside analogs share some common
      characteristics, such as requiring both transport by specific membrane
      transporters and intracellular metabolism. However, these compounds differ in
      regards to their preferential interaction with certain targets, which may explain
      why some compounds are more effective against rapidly proliferating tumors and
      others against neoplasias with a more protracted evolution. Recent progress in
      the identification and characterization of nucleoside transporters and the
      enzymes of nucleoside metabolism, as well as an understanding of the molecular
      mechanisms of anticancer nucleoside activity, provides opportunities for the
      development of new pyrimidine nucleoside analogs. Strategies to optimize
      intracellular analog accumulation and to enhance cancer cell selectivity are
      proving beneficial in clinical trials.

PMID- 14599096
TI  - Calculations of spherical aberration-corrected imaging behaviour.
AB  - Different optimal operating conditions for a C3-corrected transmission electron
      microscope were compared for both conventional field emission sources and for the
      next generation of monochromated instruments. In particular, the contrast
      transfer functions and corresponding wave aberration functions for two previously
      proposed optimal conditions in which C3 is adjusted to compensate, respectively,
      C5 or Cc are critically compared. The results indicate that in the presence of a
      small positive C5 the former provides flat transfer to the information limit
      whereas the latter shows oscillatory transfer at high spatial frequencies, which
      is more pronounced for the monochromated instrument. The effects of this
      behaviour were further investigated through multislice simulations of Si [110]
      and diamond [110] under the C5-limited condition. These confirm that for the
      former structure with an interatomic separation of 0.14 nm this aberration has
      little influence, but that for the latter with a sub-0.1 nm interatomic
      separation its presence leads to a restricted defocus range over which the
      structure is faithfully resolved.

PMID- 14599095
TI  - Advanced pancreatic cancer: is there a role for combination therapy?
AB  - Once thought to be a relatively untreatable disease, pancreatic cancer has
      recently become a focus of intense clinical research. The systemic administration
      of gemcitabine (Gemzar) is currently considered the standard first-line treatment
      for patients with advanced disease. While treatment with gemcitabine has been
      shown to result in both clinical benefit and prolongation of survival, objective
      tumor responses are relatively uncommon and median survival times remain short.
      Several recent efforts have therefore focused on evaluating chemotherapy regimens
      in which gemcitabine is combined with other cytotoxic drugs. While randomized
      trials have now confirmed that such combinations are associated with higher
      response rates, they have not yet clearly demonstrated that combination therapy
      results in a survival advantage. Increasingly, attention has turned to a number
      of novel chemotherapeutic and biologic agents that appear promising and are
      likely to play an important future role in the treatment of patients with this
      disease.

PMID- 14599097
TI  - Electrostatic mirror objective with eliminated spherical and axial chromatic
      aberrations.
AB  - Computational formulae for the coefficients of the third-order spherical
      aberration and the second-order axial chromatic aberration are presented for an
      axially symmetric electrostatic electron mirror. A technique for eliminating the
      high-order derivatives of the potential axial distribution in mirror systems from
      the integrands is described. Conditions for elimination of spherical and axial
      chromatic aberrations, either separately or simultaneously, are found for a three
      electrode axially symmetric mirror composed of coaxial cylinders of the same
      diameter. A principal scheme of the transmission electron microscope, where an
      electrostatic electron mirror serves as its objective, is presented.

PMID- 14599099
TI  - Quantitative analysis of surface atom positions in a thick crystal as determined
      by a reconstructed exit wave.
AB  - Atomic structures of an Au (110) 2 x 1 reconstructed surface were analysed
      quantitatively using an exit wave reconstructed by the three-dimensional Fourier
      filtering method in high-resolution transmission electron microscopy. To
      reconstruct the exit wave in a relatively thick crystal, a practical criterion
      was proposed in the present analysis. In the 'pseudo-exit wave' obtained by the
      proposed criterion, relaxation of surface atoms was clearly visible in the top
      three layers. The atoms' displacement was measured to be about 5-20 pm. For
      quantitative analysis of the atom column positions, image contrast calculations
      were performed using a structural model of the Au (110) reconstructed surface.
      Calculations confirmed that the reconstructed pseudo-exit wave could represent
      the atom column positions directly with an accuracy of several pm, even for a
      relaxed surface, provided the sample thickness was <7 nm.

PMID- 14599098
TI  - Profile structure of magnetic flux lines in type-II superconductor from a
      rectangular electron hologram.
AB  - Profile magnetic configuration of a quantized flux line and flux-line lattice
      penetrating a type-II superconductor thin foil, niobium, was observed by electron
      holography and Lorentz microscopy using a 300 kV field-emission electron
      microscope. Each single flux line was distributed periodically as lattice
      structure in the mixed state just below its critical temperature of 8.5 K, while
      at low temperature of 5 K the flux lines were weakly bound as bundles. In order
      to observe the flux-line distribution over a wide area, discrete Fourier
      transform reconstruction in the holography was extended for a rectangular area
      without loss of information and data precision.

PMID- 14599100
TI  - Cathodoluminescence study of AlGaAs/GaAs multilayers grown on ridge-type
      triangles on GaAs (111)A substrates.
AB  - We have studied the cathodoluminescence of AlxGa1-xAs/GaAs multilayers grown on
      ridge-type triangles by molecular beam epitaxy. The compositional variation of
      Al, as well as the distribution of impurity and/or defect, was revealed by
      variations in the cathodoluminescence spectra and images. The Al composition in
      an AlxGa1-xAs layer was highest in the (111)A facet and decreased in the order
      (100), (411)A, (111)-delta and (110) facets. On the other hand, the carbon
      concentration was highest in the (411)A facet and decreased in the order (111)A,
      (111)-delta, (100) and (110) facets. It should be noted that the (111)-delta
      facet has a significant effect on the redistribution of Al. Although our ridge
      type triangles are rather large for the quantum structures, these data have
      elucidated the self-organization mechanism of the AlxGa1-xAs/GaAs system and have
      yielded information on the design of quantum structures. We conclude that
      cathodoluminescence observation is a powerful tool for studying the compositional
      variation or band structure of three-dimensional microscale or nanoscale
      construction.

PMID- 14599101
TI  - Electron microscopic observation of 137Cs-irradiated rat testis: production of
      basal laminae for germ cells, despite their absence.
AB  - Whole body gamma-ray irradiation of rats with caesium-137 (137Cs) at embryonic
      day 20 induced marked reduction of the weight of the testis. Body weight and
      other tissues, however, seemed to remain normal. By light microscopy, complete
      loss of germ cells was observed in the testis. Other components, such as Sertoli
      cells and interstitial cells, seemed to be normal. The testes from day 8
      postpartum rats contained very few spermatogonia compared with newborn rats,
      indicating loss of germ cells between days 0 and 8. In the adult, 137Cs
      irradiated testes showed two conspicuous features other than the loss of germ
      cells: empty vacuolar spaces between Sertoli cells and multilayered seminiferous
      tubule basal laminae (lamina densa). The junctional structures (ectoplasmic
      specializations) between Sertoli cells, however, seemed normal. The thickness of
      each layer of multilayered basal laminae was the same as that of normal rats and
      electron-lucent layers similar to lamina lucida were interposed between them. Of
      the empty vacuolar spaces between Sertoli cells, basal laminae bridge the gap.
      The basal laminae contained laminin, type IV collagen and heparan sulphate
      proteoglycan evenly distributed among layers, suggesting a normal composition.
      Rough estimation of the amount of basal laminae deposited in 137Cs-irradiated
      rats indicates that it is within a range similar to that in normal testis. These
      features imply that Sertoli cells are, in part, determined perinatally to produce
      basal laminae for germ-line cells.

PMID- 14599102
TI  - Culture prior to transplantation preserves the ultrastructural integrity of
      monkey pancreatic islets.
AB  - Transplantation of pancreatic islets represents a promising way of curing type I
      diabetes (insulin-dependent diabetes mellitus). Culture enables the survival of
      endocrine tissue awaiting islet transplantation and reduces islet immunogenicity
      prior to xenografting. In this study, attempts were made to preserve the monkey
      islets in culture for 7 days and to study the ultrastructure by electron
      microscopy. The islets were isolated from monkey pancreas by the collagenase
      digestion method and were separated from acinar cells by dextran density gradient
      centrifugation. These islets were preserved in a humidified atmosphere of 5%
      carbon dioxide and 95% air for 7 days. The culture medium used was CMRL-1066.
      After 7 days of culture the islets were processed for light and electron
      microscopic studies, which revealed that the cultured islets were intact and
      maintained their structural integrity. Semi-thin sections of the cultured islets
      showed morphology with occasional structural alterations at the periphery.
      Dithizone staining of the cultured islets showed crimson red colour, proving that
      the islets were pure and without any exocrine contamination. Electron microscopy
      showed that the cultured islets had well-preserved alpha-, beta- and delta-cells.
      Different cell types of the monkey pancreatic islets were identified by the
      presence of their characteristic secretory granules. The ultrastructural
      characteristics present in hormone-synthesizing cells, i.e. rough-endoplasmic
      reticulum, Golgi apparatus, mitochondria and secretory granules, were observed as
      in native islets.

PMID- 14599103
TI  - Histological study of experimental murine AA amyloidosis.
AB  - The localization of amyloid fibril components and the cells related to the
      formation and resorption of the fibrils are still controversial. We conducted a
      time-kinetic study to analyse the process of amyloid fibril deposition in the
      spleen of an AA amyloidosis animal model immunohistochemically. Murine AA
      amyloidosis was induced by an emulsion injection composed of Freund's complete
      adjuvant and Mycobacterium butyricum. The serum amyloid A level was the highest
      at 3 days after the induction and gradually decreased. The amyloid deposition was
      first detected in extracellular spaces in the marginal zone of the spleen at 7
      days after induction. F4/80 positive red pulp macrophages increased in number
      after the induction and accumulated near the amyloid deposition areas. Amyloid P
      component (APC) and chondroitin sulphate proteoglycan (CSPG), which are composed
      of amyloid fibril, were detected in the cytoplasm of F4/80 positive red pulp
      macrophages and ER-TR9 positive marginal zone macrophages, respectively, then
      localized in the amyloid deposition areas. APC was also localized in CSPG
      positive and F4/80 negative cells, which might be fibroblasts at 3 days. These
      results suggest a close association of APC positive/ER-TR9 positive macrophages
      and APC positive/CSPG positive fibroblasts in the formation of amyloid fibrils
      and F4/80 positive macrophages with the resorption of fibrils.

PMID- 14599104
TI  - On-substrate lysis treatment combined with scanning probe microscopy revealed
      chromosome structures in eukaryotes and prokaryotes.
AB  - The proper function of the genome largely depends on the higher-order
      architecture of the chromosome. To understand the detailed chromosome structure
      in a native state, we developed an on-substrate procedure of subcellular
      fractionation suitable for the observation by atomic force microscopy (AFM). HeLa
      cells on a coverslip were successively treated with a detergent and a high-salt
      solution to remove the cytoplasmic and nucleoplasmic materials. A closer
      observation of the nucleus by AFM revealed that the interphase chromosome is
      composed of a granular unit of approximately 80 nm in diameter. Subsequent mild
      treatment with deoxyribonuclease I (10 U ml(-1)) exposed these units more
      clearly, which enabled us to uncover the 80-nm granules forming a fibre of
      approximately 80 nm width. In the cytoplasmic regions, cytoskeletal fibres with
      varying widths (10-70 nm) were observed. These observations suggest that the 80
      nm granular fibre is a fundamental structural unit of the interphase chromosome.
      This on-substrate procedure was also applied to Escherichia coli. Cells attached
      on a coverslip were successively treated with lysozyme and detergent to partially
      release the nucleoid onto the substrate. The AFM observation revealed that the
      approximately 80 nm fundamental structural unit forms a granular fibre similar to
      that of HeLa cells. These results suggest that the fundamental mechanism of
      chromosome packing is common in both prokaryotes and eukaryotes.

PMID- 14599105
TI  - Complementary techniques for unbiased stereology of brain ultrastructure.
AB  - Estimating synaptic density is central to any examination of synaptic change.
      Barring techniques involving exhaustive sectioning, the traditional method for
      this estimation is the double dissector technique, which derives a ratio of
      synapses per neuron. This ratio, however, may not always equate to an absolute
      number of synapses. In contrast, the unbiased brick, while free of these
      problems, is limited by changes in reference space and cannot provide information
      on synaptic connectivity. Thus, the ideal analysis is to derive both synaptic
      measures. When these measures agree, one can discount changes in extraneous
      factors influencing synaptic counts.

PMID- 14599106
TI  - Comparison of hexamethyldisilazane and critical point drying treatments for SEM
      analysis of anaerobic biofilms and granular sludge.
AB  - We present a fast procedure for scanning electron microscopy (SEM) analysis in
      which hexamethyldisilazane (HMDS) solvent, instead of the critical point drying,
      is used to remove liquids from a microbiological specimen. The results indicate
      that the HMDS solvent is suitable for drying samples of anaerobic cells for
      examination by SEM and does not cause cell structure disruption.

PMID- 14599107
TI  - Comparison of the thickness of basement membranes in various tissues of the rat.
AB  - The thicknesses of the lamina lucida and the lamina densa of basement membranes
      in various kinds of tissues, including the epidermis and mucosal epithelium, and
      basement membranes adjacent to a Schwann cell, perineurial sheath cell,
      endothelial cell, pericyte, muscle cell and fat cell, were compared on high
      powered transmission electron micrographs. Each tissue and cell possessed a
      basement membrane with thicknesses of the lamina lucida and lamina densa that
      were specific to the particular tissue or cell. This indicates that the lamina
      lucida and lamina densa of the basement membrane of a tissue/cell have a
      particular constitution. New theories on the molecular constitution between the
      cell surface and basement membrane may need to be developed.

PMID- 14599108
TI  - Estrogen and non-feminizing estrogen for Alzheimer's disease.
AB  - The preventive effect of estrogen on Alzheimer's disease (AD) has become clearer
      with many epidemiological reports. However, the therapeutic effects of estrogen
      have been controversial until now. In our trials, estrogen treatment showed a
      beneficial therapeutic effect for women with mild to moderate AD. Improvement of
      cognitive function was recognized during the third week from the beginning of
      administration and maintained as long as estrogen treatment continued. The longer
      the duration of HRT, the more HRT is useful for the prevention and therapy of AD.
      However, in most cases, administration of estrogen is discontinued because of the
      adverse effects on the uterus and breast. J 861 is a derivative of estradiol
      17alpha, which has little effect on the sexual organs. The effects of estradiol
      17beta (E2) and J 861 on neuronal function and vascular factors were
      investigated. J 861 was suggested to prevent both the intracellular calcium
      increase and peroxidation induced by amyloid beta (Abeta), more effectively than
      E2. The effect of J 861 may be related with both the direct non-genomic and the
      ER-mediated systems. J 861 showed neurotrophic effects like E2. J 861 inhibited
      the adhesion of monocytes to vascular endothelium, more effectively than E2.
      Also, J 861 suppressed the expression of adhesive factors, such as E-selectin and
      intercellular cell adhesion molecule-1 (ICAM-1), more effectively than E2.

PMID- 14599109
TI  - Recent advances in the management of primary hyperparathyroidism.

PMID- 14599110
TI  - Persistence of mild hyperthyrotropinemia after discontinuation of three-year
      course of low-dose L-thyroxine therapy in infants with borderline hypothyroidism.
AB  - Treatment plan for neonates with borderline hypothyroidism (persistent
      hyperthyrotropinemia with normothyroxinemia) has not been established. In this
      study, changes in thyroid function after discontinuation of low-dose L-thyroxine
      (L-T4) supplement in infants with the condition were evaluated. Fourteen infants
      with hyperthyrotropinemia at neonatal screening had repeated hyperthyrotropinemia
      (> 8 mU/L) with normothyroxinemia. TSH response was exaggerated at TRH testing.
      The subjects were treated with low-dose L-T4 (3 to 9 microg/kg/day) for 2.2 to 6
      years, and euthyroid status was maintained. After discontinuation of therapy,
      mild hyperthyrotropinemia persisted up to 24 months, while serum FT4 remained
      within the lower half of the normal range. TSH response to TRH stimulation, which
      tended to be exaggerated 1 month after discontinuation, became lower 6 to 12
      months later. RAIU and thyroid scintigraphy were normal in all subjects. No
      patient developed hypothyroxinemia, although mild elevation of TSH lasted rather
      long after discontinuation of low-dose L-T4 therapy. Administration of L-T4 was
      not resumed provided the subjects were followed at regular interval. Further long
      term investigation is needed to define whether re-administration is necessary or
      not.

PMID- 14599111
TI  - Two cases of monostotic Paget's disease: effects of bisphosphonate.
AB  - We report two cases of monostotic Paget's disease which were effectively treated
      with bisphosphonate. Case 1 was a 60-year-old female. Medical examination
      revealed high alkaline phosphatase (ALP) levels making her visit our clinic.
      Hematological examination showed high levels of ALP isozyme 3 and bone metabolism
      markers, and bone scintigraphy demonstrated strong accumulation of 99mTc on the
      skull. With the diagnosis of monostotic Paget's disease of the skull, treatment
      with bisphosphonate (etidronate) was started. The response to etidronate was good
      and after 12 weeks of treatment, the ALP levels decreased to about 26% of the
      levels before treatment, without the appearance of any symptoms or lesion
      development. One year and three months later, ALP increased again, and etidronate
      administration was resumed. However, four years after the diagnosis of the
      disease, etidronate became ineffective and oral administration of alendronate, a
      stronger bisphosphonate, was started at 5 mg/day. The patient responded favorably
      to the bisphosphonate and is still under observation. Case 2 was a 71-year-old
      female. High ALP levels were found during the follow-up of type 2 diabetes, and
      the case was diagnosed as monostotic Paget's disease of the pelvis based on bone
      metabolism markers and bone scintigraphy. Etidronate treatment at 200 mg/day
      resulted in the improvement of bone metabolism markers and bone scintigraphy
      findings. When she died of colon cancer twelve months later, with no marked
      progress of the Paget's disease of bone observed clinically.

PMID- 14599112
TI  - The D allele of the angiotensin-converting enzyme insertion/ deletion (I/D)
      polymorphism is a risk factor for type 2 diabetes in a population-based Japanese
      sample.
AB  - The association of the ACE gene I/D polymorphism with type 2 diabetes (DM) was
      examined in a population-based Japanese sample. A total of 902 individuals (490
      females and 412 males, age 58.8 +/- 12.2 yr) from a cohort population (n = 3,706)
      of the Funagata diabetes study were divided into three groups according to
      genotype: D/D (n = 104), I/D (n = 436) and I/I (n = 362). Chi-square test and
      ANOVA were used for association studies and to assess the differences in the
      traits' values, respectively. More individuals with the genotypes D/D and I/D
      were diabetic (8.7% and 4.1%, respectively) than those with the genotype I/I
      (2.8%, p = 0.008 and p = 0.032, respectively). The genotype D/D was a risk factor
      for DM (relative risk (RR) 3.13, 95% CI 1.31-7.51), and also for DM and IGT (RR
      1.78, 95% CI 14-2.76). Multiple logistic regression analysis also showed that the
      genotypes with the D allele were risk factors for DM and IGT even when adjusting
      for age, sex, hypertension and serum total cholesterol levels (odds ratio 1.49,
      95% CI 1.01-2.21). The D allele of the ACE gene I/D polymorphism is a risk factor
      for DM.

PMID- 14599113
TI  - Prevalence of subclinical Cushing's syndrome in 70 patients with adrenal
      incidentaloma: clinical, biochemical and surgical outcomes.
AB  - Subclinical Cushing's syndrome (SCS) is being detected with increased frequency
      in patients with adrenal incidentaloma. In the current study, we evaluated the
      prevalence of SCS in 70 patients with adrenal incidentaloma and compared the main
      findings on them with other patients with nonfunctional adrenal incidentaloma
      (NFA). Overnight 3 mg dexamethasone (DXM) suppression test to exclude cortisol
      hypersecretion, and high dose DXM suppression test to find out patients with SCS,
      were applied to all subjects. Afterwards, biochemical and clinical findings of
      patients with SCS were compared with the other patients with NFA. Four of the 70
      patients with adrenal incidentaloma were found to have SCS, with a prevalence of
      5.7%. Basal ACTH and DHEA-S levels were significantly lower (p < 0.05 and p <
      0.01, respectively), and midnight cortisol and 24-hour urinary free cortisol
      levels were significantly higher in patients with SCS (p < 0.001 and p < 0.05,
      respectively). Biochemical and metabolic bone parameters were similar in patients
      with SCS and in patients with NFA. Hypertension, diabetes mellitus, and obesity
      were more common in patients with SCS. One of the patients with SCS developed
      adrenocortical insufficiency following unilateral adrenalectomy which lasted for
      about 6 months. Suppressed ACTH and DHEA-S levels, and high midnight cortisol
      levels may be some clues for SCS in patients with adrenal incidentaloma. Since
      patients with SCS frequently have risk factors for atherosclerosis such as
      hypertension, diabetes, and obesity, and the surgical management of SCS with
      adrenalectomy may offer an advantage. Patients undergoing adrenalectomy should be
      followed for the development of adrenal insufficiency.

PMID- 14599114
TI  - Thyroid hemiagenesis with multinodular goiter: a case report and review of the
      literature.
AB  - Thyroid hemiagenesis is a very rare abnormality, in which one thyroid lobe fails
      to develop. Most of the patients diagnosed have an associated thyroidal disease.
      The true prevalence of thyroid hemiagenesis is not known, but it is estimated to
      be 0.02% in normal children. We report a forty-five year-old female patient with
      a multinodular goiter in left lobe, associated with hemiagenesis of right lobe
      and isthmus.

PMID- 14599115
TI  - A case of Sheehan's syndrome with panhypopituitarism due to the impairment of
      both the hypothalamus and the pituitary.
AB  - Sheehan's syndrome is thought to be caused by pituitary necrosis associated with
      massive hemorrhage at delivery. We report here on a patient with Sheehan's
      syndrome, showing a rare type of panhypopituitarism suggesting dysfunction of
      both the hypothalamus and the pituitary. Although the basal level of plasma ACTH
      was normal, that of plasma cortisol was low. ACTH showed a delayed high response
      to CRH and a low response to insulin-induced hypoglycemia, while plasma cortisol
      showed a low response to CRH and no response to insulin-induced hypoglycemia. In
      the standard ACTH test, a normal rise of plasma cortisol was found. These results
      indicate that the primary site responsible for hypothalamic-pituitary
      adrenocortical hypofunction may be the hypothalamus. In addition, the dysfunction
      of the pituitary itself is suggested by the hyposecretion of other pituitary
      hormones with impaired responses in their provocative tests and partially empty
      sella.

PMID- 14599116
TI  - Free-to-total leptin ratio in maternal plasma is constant throughout human
      pregnancy.
AB  - To clarify the mechanism of leptin resistance during pregnancy, we measured
      plasma leptin concentrations, free to total leptin ratio (percent free leptin)
      and soluble leptin receptor concentrations in pregnant women, and compared the
      results with those in non-pregnant women. We collected plasma samples from 23 non
      pregnant and 31 pregnant women in the third trimester. Plasma samples from 5
      pregnant women were collected longitudinally in each trimester. Plasma leptin
      concentrations in pregnant women in the second trimester (17.4 +/- 3.2 ng/ml)
      were higher than those in the first trimester of pregnancy (11.0 +/- 2.8 ng/ml, n
      = 5), as previously reported. However, percent free leptin did not change
      significantly throughout pregnancy. Percent free leptin correlated with total
      leptin concentrations (ng/ml) in non-pregnant women (r = 0.727, P < 0.0001), but
      not in women in the third trimester of pregnancy (r = 0.006). Constant percent
      free leptin during pregnancy despite increased leptin concentrations indicates
      increased leptin binding capacity in pregnant women, that might partly contribute
      to the establishment of leptin resistance. On the other hand, soluble leptin
      receptor concentrations showed significant negative correlation with BMI and
      plasma leptin concentrations in pregnant women (r = -0.470, P < 0.01 and r = 
      0.493, P < 0.01, respectively) but not in non-pregnant women. These data suggest
      the possibility that soluble leptin receptor is a minor component of leptin
      binding capacity in the plasma of pregnant women.

PMID- 14599117
TI  - Prevalence and clinico-epidemiology of familial Graves' disease in Japan based on
      nationwide epidemiologic survey in 2001.
AB  - A nationwide epidemiologic survey of familial Graves' disease (GD) was conducted
      in 2001. "Familial GD" was defined as a patient who had at least one Graves'
      patient within the proband's first-degree relatives. The primary survey was
      performed for estimating the prevalence of patients among a random selection of
      2367 departments/hospitals of internal medicine, endocrinology, thyroidology and
      pediatrics. Of those receiving the primary questionnaire, 1361 (57.5%) responded,
      and 902 familial GD patients who visited them in 2000 were reported. The total
      number of patients was estimated to be 2850 (95% confidence intervals: 2100
      3600). Based on the nationwide survey concerning the prevalence of
      hyperthyroidism in 1999, 2.1-3.1% of hyperthyroidism appeared to be familial GD
      and the relative risk of familial GD was roughly estimated to be 19-42.
      Subsequently, a second survey was carried out for obtaining the
      clinicoepidemiologic features of those patients. Of 902 patients, 487 (54%) were
      reported. No significant differences between familial and non-familial GD were
      found in age and sex distributions, clinical features or laboratory findings.
      Familial GD possessed the highest association with Hashimoto's thyroiditis,
      approximately 8% within the first-degree relatives, suggesting a shared genetic
      predisposition. These findings confirm the familial clustering of GD in the
      Japanese population, indicating the importance of environmental factors, genetic
      factors or both in the development of the disease.

PMID- 14599118
TI  - Oral DDAVP is a good alternative therapy for patients with central diabetes
      insipidus: experience of five-year treatment.
AB  - We studied the efficacy and safety of oral 1-deamino-8-D-arginine-vasopressin
      (DDAVP) tablets in 9 patients, aged 17-36 years, with central diabetes insipidus
      (DI). The tablet contained 100 microg of desmopressin acetate. Maximum plasma
      concentration was obtained at 90 min after a single oral administration of 100
      microg DDAVP with a mean plasma level of 14.7 +/- 5.4 (range: 5.3-50.9) pg/ml.
      The onset of action was observed 2 h after oral administration, while the maximum
      effect was obtained at 4 h. Mean urine volume in patients decreased significantly
      from 402 +/- 52 to 26 +/- 3 ml/hr and urine osmolality increased from 91 +/- 8 to
      732 +/- 21 mosm/kg at 4 h after the intake of oral DDAVP. Plasma osmolality level
      and serum sodium concentration remained unchanged throughout the study. Long-term
      treatment for 5 years with oral DDAVP resulted in control of diuresis in 8 of the
      9 patients. The average oral DDAVP dose required to obtain this control was 19 +/
      2 (range: 15-30) times more than that of prior intranasal treatment. No adverse
      effects were observed during this follow-up period. These results indicate that
      oral DDAVP is a safe therapeutic agent that may be a good alternative treatment
      of central DI, particularly in patients who have chronic rhinitis and visual
      disturbances.

PMID- 14599119
TI  - Expression of 11 beta-hydroxysteroid dehydrogenase type 1 in alveolar epithelial
      cells in rats.
AB  - 11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD1) behaves predominantly as
      an oxoreductase converting the receptor-inactive glucocorticoids to their active
      forms in vivo, while the type 2 isoform (11beta-HSD2) possesses only
      dehydrogenase activity and inactivates cortisol in human or corticosterone in
      rat. We determined enzyme activity of 11beta-HSD in rat lungs from fetus to
      adult, and examined whether 11beta-HSD1 exists in alveolar type II cells, the
      most important site for the synthesis of pulmonary surfactant in mature lungs, by
      immunohistochemistry and reverse transcription-polymerase chain reaction (RT
      PCR). Enzyme activity of 11beta-HSD1 and 2 in lung tissue homogenate were
      determined as NADP(+)- and NAD(+)-dependent conversion of corticosterone to 11
      dehydrocorticosterone, respectively. We found that 11beta-HSD1 activity was
      increased progressively from 21 days gestation to 7 weeks after birth. 11beta
      HSD2 activity was significantly lower than that of 11beta-HSD1 throughout
      gestation and after birth. Immunoreactivity for 11beta-HSD1 was detected in the
      cytoplasm of the cells in the alveolar region of adult rats. Some of these
      expressing 11beta-HSD1 were considered to be alveolar type II cells, because of
      their cuboid shape and localization at the corner of the alveoli. RT-PCR
      demonstrated 11beta-HSD1 mRNA in isolated alveolar type II cells. Our results
      suggest that alveolar type II cells enhance intracellular glucocorticoid
      availability via 11beta-HSD1. 11beta-HSD1 in alveolar type II cells is thought of
      as an autocrine amplifier of glucocorticoid action in the lung.

PMID- 14599120
TI  - Mild persistent hypercalcitoninemia after total thyroidectomy in patients with
      papillary thyroid carcinoma.
AB  - Total thyroidectomy was performed in 455 patients with differentiated thyroid
      carcinoma between 1978 and 1999. Serum calcitonin (CT) was determined
      preoperatively in all patients using polyclonal antibodies. Among the subjects,
      25 patients showed elevated serum calcitonin levels preoperatively. Pathological
      diagnoses of 18 patients were confirmed as medullary thyroid carcinoma (MTC)
      postoperatively. Eight patients were diagnosed as papillary thyroid carcinoma
      (PTC) in the final pathological diagnosis without evidence of minimal foci of MTC
      or C cell hyperplasia, and they showed elevated CT levels preoperatively.
      Hypercalcitoninemia in 8 patients with PTC continued through out the 24 follow-up
      months with normal CEA levels. Extrathyroidal CT-producing diseases were all
      neglected, and precise pathological examination showed negative evidence of
      minute MTC or C cell hyperplasia in these 8 patients. Serum CT levels were
      simultaneously determined by a different CT assay kit using the same blood
      samples in 7 of 8 patients. Serum CT levels were all within normal values in
      another CT kit applying a different polyclonal antibody, although elevated CT
      values continued in the routine CT kit. The recognition of polymeric or
      fragmented CT by polyclonal antibody was thought to be the causative factor for
      the hypercalcitoninemia after total thyroidectomy in the patients with PTC.
      Knowledge of the false positive CT determination makes it important to employ
      different CT assay kits, especially the new generation of two-site immunoassays
      using two monoclonal antibodies against distinct epitopes of human CT, although
      the new generation kits are not clinically available in Japan.

PMID- 14599121
TI  - Gene expression study of thyrotropin releasing hormone (TRH) receptor using RT
      PCR: relationship to clinical and immunohistochemical phenotypes in a series of
      human pituitary adenomas.
AB  - Thyrotropin releasing hormone receptor 1 (TRHR1) and 2 (TRHR2) mRNAs were
      examined using reverse transcription polymerase chain reaction (RT-PCR). These
      data were then correlated with endocrinological and histological characteristics
      in 65 human pituitary adenomas including one non tumorous pituitary gland, to
      clarify the role of TRHR1 and 2 gene expression in human pituitary adenomas,
      especially as it relates to the paradoxical stimulatory effects of TRH found in
      pituitary adenomas. TRHR mRNA was not identified in four ACTH cell adenomas,
      whereas TRHR mRNA expression was found in 12/23 acromegaly specimens, 7/8
      prolactinomas, 3/3 TSH cell adenomas, and 22/27 clinically nonfunctioning
      adenomas. Specimens obtained from patients expressing the TRHR gene were found to
      express TRHR1 and TRHR2 or TRHR1 alone, whereas no cases were identified in which
      TRHR2 alone was expressed. In examining the relationship between GH, PRL, TSH, or
      gonadotropin subunit response to TRH administration and TRHR gene expression,
      TRHR mRNA was found to be absent in 9 out of 10 GH cell adenomas without
      paradoxical GH response to TRH (non-responder), whereas TRHR genes were shown to
      be expressed in 10 out of 12 GH cell adenomas with paradoxical GH response to TRH
      (responders) (chi2 = 11.73, p = 0.0009). However, there was no significant
      correlation between TRHR gene expression and responsiveness to PRL or
      gonadotropins to TRH administration in PRL cell adenomas (chi2 = 0.16, p = 0.87)
      or gonadotroph cell adenomas (chi2 = 0.0006, p = 1), respectively. We concluded
      that the existence of the TRH receptor in adenoma cells plays an important role
      in the paradoxical GH response to TRH administration in GH cell adenomas. It
      should be noted that the PRL response to TRH in prolactinoma or an abnormal
      response of gonadotropin and/or its subunits to TRH in gonadotroph cell adenomas
      is considered to be due to a mechanism other than direct TRH action in adenoma
      cells. However, further studies are required to elucidate the role of TRHR2 in
      pituitary adenomas.

PMID- 14599122
TI  - Aplastic anemia during growth hormone (GH) treatment in a girl with idiopathic GH
      deficiency.
AB  - We report a 12-year-old girl with aplastic anemia accompanied by chromosome 8
      trisomy during growth hormone (GH) therapy. When she was six years old she was
      diagnosed as idiopathic isolated GH deficiency, and GH therapy (0.175 mg/kg/week)
      was initiated. At the age 12, she began to exhibit petechiae in both lower limbs.
      Platelet count was 11,000/microL; serum hemoglobin level 11.8 gr/mL; white blood
      cell count 3,400/microL, with 37% neutrophils, 58% lymphocytes, 4% monocytes and
      1% basophils. Bone marrow examination showed that total nucleated cell count and
      megakaryocyte were 17,000/microL and 0/microL, respectively, suggesting low
      formation. In addition, 13% of bone marrow cells contained the 3 signals of
      chromosome 8 marker (trisomy 8). She was diagnosed as aplastic anemia accompanied
      with chromosome 8 trisomy. GH therapy was stopped immediately, and simultaneous
      administration of methylprednisolone and anti-thymocyte globulin was initiated.
      Platelet count improved with treatment, and the 3-signal chromosome 8 abnormality
      disappeared from the bone marrow cells. The fact that a hematological adverse
      effect other than leukemia exists in conjunction with GH therapy warrants further
      investigation into possible hematological changes occurring during or after GH
      therapy.

PMID- 14599124
TI  - Double parathyroid carcinoma.
AB  - The incidence of parathyroid carcinoma is rare. We recently encountered a case of
      double carcinoma, located in the right and left upper parathyroid glands. A 67
      year old man came to the Teikyo University Hospital because of his bilateral
      parathyroid masses with hypercalcemia and high parathyroid hormone (PTH).
      Preoperative diagnoses were parathyroid adenoma in the left lobe and papillary
      thyroid carcinoma or parathyroid carcinoma in the right lobe. First, the left
      tumor was removed; however, iPTH was still high. The right mass was then resected
      and iPTH fell to normal range. Histological examination revealed both tumors were
      parathyroid carcinoma. To the best of our knowledge, this is the first report of
      double parathyroid carcinoma confirmed histologically.

PMID- 14599123
TI  - Two novel aquaporin-2 mutations in a sporadic Japanese patient with autosomal
      recessive nephrogenic diabetes insipidus.
AB  - We identified two novel mutations of the aquaporin-2 (AQP2) gene in a sporadic
      Japanese patient diagnosed with an autosomal recessive nephrogenic diabetes
      insipidus (NDI). The patient, a Japanese boy, was referred to our clinic at the
      age of 5 months because of unexplained recurrent fever. He was diagnosed with NDI
      by clinical, biochemical and endocrine findings. Molecular analysis demonstrated
      that he was a compound heterozygote for two mutations. One mutation consisted of
      a two base deletion in exon 1 (197, 198 delCA). This deletion caused a frameshift
      in the open reading frame, resulting in a premature stop codon 186 bases
      downstream in exon 1. The second mutation was a G to A transition of the terminal
      exon splice site (1502-1G-->A). To date, several mutations in the AQP2 gene have
      been described, however no splicing mutation in the AQP2 gene has been
      identified. The deletion mutation described in this case study was inherited
      patemally and the splicing site mutation was inherited maternally, indicating an
      autosomal recessive inheritance. In the present case study, we identified two new
      mutations in the AQP-2 gene. Previous studies have shown that there is no hot
      spot for mutations in the AQP-2 gene, and thus genetic analysis for individual
      patients is helpful for genetic counseling and early diagnosis.

PMID- 14599125
TI  - Leukocytosis-induced artifactual hypoglycemia.

PMID- 14599126
TI  - A case of megaloblastic anemia due to vitamin B12 deficiency precipitated in a
      totally gastrectomized type II diabetic patient following the introduction of
      metformin therapy.

PMID- 14599127
TI  - An Internet otolaryngology referral center: a preliminary report.
AB  - BACKGROUND: The aim of this study was to review our early experience with the
      UPenn Otolaryngology Referral Center Website, ENTConsult.org. METHODS:
      ENTConsult.org is an interactive website that allows a referring physician to
      select a University of Pennsylvania Health System otolaryngologist and share
      clinical information, including uploaded pictures, radiographs, and other images
      via the Internet. Traditional methods of long-distance consultation involve
      mailing clinical information, which often is slow and unwieldy, thus discouraging
      consultation. ENTConsult.org seeks to take advantage of Internet functionality to
      facilitate efficient and timely consultation regardless of any of the
      participants' locations. RESULTS: In this report we reviewed our initial
      experience with ENTConsult.org, including an overview of the website
      functionality and a detailed review of critical logistical considerations.
      CONCLUSION: The UPenn Otolaryngology Referral Center Website ENTConsult.org
      offers considerable promise as an avenue for long-distance referral and
      consultation.

PMID- 14599128
TI  - Comparative karyometric study of the glandular epithelium of normal nasal mucosa
      and rhinosinus polyposis.
AB  - BACKGROUND: Rhinosinus polyposis, characterized by a degeneration of the nasal
      mucosa of the middle meatus, is poorly understood but probably is correlated with
      several clinical and etiopathogenic entities. Although not definitely
      characterized, infectious, atopic, inflammatory, genetic, and other factors are
      involved. The occurrence of malignant degeneration also has been suggested.
      METHODS: To contribute to the elucidation of the etiopathogenicity of rhinosinus
      polyps, we performed a karyometric analysis of their glandular mucosa compared
      with the normal mucosa. RESULTS: A significant increase in nuclear volume was
      observed, which was not accompanied by changes in shape. CONCLUSION: The results
      suggest that nuclear alterations may contribute to the pathogenicity of this
      condition.

PMID- 14599129
TI  - Nasal cytology: description of a hyperchromatic supranuclear stria as a possible
      marker for the anatomical and functional integrity of the ciliated cell.
AB  - BACKGROUND: The aim of this study was to describe a particular intracellular
      hyperchromatic formation located over the nucleus of normal nasal ciliated cells.
      This finding, never described in literature, very rarely occurs in pathological
      conditions. METHODS: A nasal cytological test and mucociliary transport test were
      performed in a group of 24 subjects with rhinologic diseases and in a control
      group of 10 healthy subjects. RESULTS: The "hyperchromatic supranuclear stria"
      (SNS) was observed in a high percentage of normal cells (90.3%); SNS was present
      in very few pathological subjects (in only 6.26% of pathologic cells).
      CONCLUSION: We interpreted SNS as a specific marker for the anatomic and
      functional integrity of the ciliated cell. Therefore, the absence of SNS is
      considered an abnormal finding in the nasal mucosa and therefore could be useful
      as a "prognostic sign" of the disorders themselves and as an indication of the
      "therapeutic efficacy" of pharmacologic treatments, both topical and systemic.

PMID- 14599130
TI  - Nitric oxide and collagen expression in allergic upper-airway disease.
AB  - BACKGROUND: The presence of nitric oxide (NO) in high concentrations has been
      described in the nasal mucosa of patients with untreated allergic rhinitis. We
      sought to examine the role of exogenous, as well as endogenous, NO in the
      production of collagen type I and type III by human nasal fibroblasts. METHODS:
      Primary cultured fibroblasts derived from eosinophilic nasal polyps were exposed
      to NO donors (500 microM of S-nitroso-N-acetyl-D,L-penicillamine (SNAP) 1000
      micoM of 3,3-bis(aminoethyl)-1-hydroxy-2-oxo-1-triazene (DETA-NONOate)) and
      various other compounds over a 24-hour incubation period. Collagen production was
      evaluated qualitatively by immunocytochemistry and quantitatively by Western blot
      analysis. RESULTS: Maximally stimulated fibroblasts established a 2,2-fold
      increase in the production of type III collagen relative type 1, as compared with
      baseline. Oxyhemoglobin, an NO scavenger, abolished this effect. SNAP (500
      microM) caused a 15.68 +/- 0.68% increase in collagen type I synthesis as
      compared with unstimulated controls (p < 0.05). In contrast, incubation with SNAP
      caused an increase in collagen type III production by a factor of 34.68 +/- 0.32%
      (p < 0.05). CONCLUSION: NO stimulates collagen expression in human nasal polyp
      derived fibroblasts. This stimulation appeared to favor the up-regulation of
      collagen type III, leading to a shift in the ratio of collagen type I to type III
      production.

PMID- 14599131
TI  - Facial growth after middle turbinate resection: an experimental study in the
      rabbit.
AB  - BACKGROUND: The aim of this study was to determine the effects of total middle
      turbinate resection on midfacial growth through a morphometric analysis on an
      animal model. METHODS: Twenty-eight male New Zealand white rabbits were used. The
      animals were divided into three groups: group 1, elevation and relocation of the
      nasal bone was performed; group 2, concha resection was performed; group 3,
      control group with no surgical procedure. The surgery was done at 8-10 weeks of
      age and the skull of each subject was sampled as they reached maturity. The
      determined distances then were measured by using landmarks identified on skull.
      The supplied data were evaluated by using the Mann-Whitney U test. RESULTS:
      Deviation of the nasal axis to the opposite side of the resected concha and an
      increase in the width of nasal bone were observed only in group 2. In group 1, an
      increase of nasal bone length and zygomaticonasal distances was determined in
      both the operated and the unoperated sides of nasal bones. CONCLUSION: This
      animal experiment showed that operations on the nasal bone or concha resection
      affected the midfacial growth in rabbits. The effects of middle turbinate
      resection to midfacial development should be evaluated by additional studies. We
      recommend only limited, conservative surgical procedures on the middle turbinate,
      saving all the vital mucosa, periosteum, and bone.

PMID- 14599132
TI  - Virtual simulator as a training tool for endonasal surgery.
AB  - BACKGROUND: Virtual simulation could be an important tool for medical and
      surgical training as well as education. The efficacy of a simulator for
      endoscopic nasal procedures in a training program was evaluated. METHODS: The
      simulator is a medical and scientific tool for visualizing and interacting with
      three-dimensional volumetric data. Twenty endonasal operations with chronic
      rhinosinusitis were simulated by two 3rd-year residents and proctored by the
      senior surgeon 1 day before the actual surgery was performed with an endoscope
      and computer-aided surgery. A questionnaire was established. RESULTS: The
      surgical simulator may provide a better understanding of the morphology of the
      paranasal sinuses with a minor impact on performance of endoscopy by junior
      residents. Disadvantages identified were time consumption, absence of force
      feedback, and subtle handling of the joysticks. CONCLUSION: The virtual simulator
      allows the nonendoscopically nasal trained surgeon to understand and practice
      endonasal surgery using real-patient data but failed to make an impact on
      operating room performance. Furthermore, the simulator's effectiveness was
      limited by the absence of force feedback, subtle handling of the joysticks, and
      considerable time consumption.

PMID- 14599134
TI  - The bath-plug closure of anterior skull base cerebrospinal fluid leaks.
AB  - BACKGROUND: This study presents the technique and results of cerebrospinal fluid
      (CSF) leak closure by placement of a fat plug on the intracranial surface of the
      dura. A prospective cohort study of all consecutive patients undergoing
      endoscopic closure of an anterior skull base CSF leak using the bath-plug
      technique was performed at a tertiary care center. METHODS: Thirty-three patients
      presented with CSF leaks: 6 were traumatic, 7 were spontaneous, 9 were
      iatrogenic, and 10 were associated with a meningoencephalocele. The average age
      of the patients was 40 years and the male-to-female ratio was 1.2:1. All patients
      underwent the bath-plug technique for closure of CSF leaks. The surgical
      technique was presented. RESULTS: Thirty-one of the 33 patients had a successful
      primary closure of their CSF leak with 2 patients requiring a repeat procedure.
      After an average of 28 months follow-up, there were no recurrent leaks in any of
      the patients. This gives a primary closure success rate of 94% and a secondary
      closure rate of 100%. CONCLUSION: The bath-plug technique for closure of anterior
      skull base CSF leaks was a reliable technique for a large variety of causes.

PMID- 14599133
TI  - Outcome of computer-assisted sinus surgery: a 5-year study.
AB  - BACKGROUND: The aim of this work was to study the outcome and rate of
      complications in a cohort of patients who underwent computer-assisted surgery
      (CAS). A retrospective study was performed of all patients undergoing CAS at a
      tertiary care teaching hospital over a 5-year period. METHODS: All patients who
      underwent computer-assisted sinus surgery with at least 1 year of follow-up were
      included in the study. Charts were reviewed for indication of CAS, incidence of
      major complications, and need for revision surgery after CAS. RESULTS: A total of
      120 patients underwent CAS in the 5-year period. Ten patients were lost to follow
      up and were not included in the analysis. Indications for the use of CAS were
      revision surgery in 85 patients, sphenoid sinus disease in 12 patients, isolated
      frontal sinus disease in 4 patients, combined sphenoid and frontal disease in 2
      patients, and cerebrospinal fluid leak (CSF) leak in 7 patients. The mean
      postoperative follow-up was 2.6 years. There were no major complications. Fifteen
      (16.5%) patients required revision surgery: 10 patients required revision
      endoscopic sinus surgery (1-5 revisions using CAS), 3 patients required an
      external open procedure, and 3 patients required revision CSF leak closure (one
      patient required both revision sinus surgery and an external procedure). There
      were no cases of major intra- or postoperative bleeding, central nervous system
      damage, CSF leak, or orbital trauma in this study. CONCLUSION: CAS helps in
      avoiding trauma to the orbit and anterior skull base and has a low incidence of
      major complications. The need for revision surgery may occur in patients with
      frontal sinus disease, nasal polyposis, or recurrent CSF leak.

PMID- 14599135
TI  - The risk of olfactory disturbance from conchal plate injury during ethmoidectomy.
AB  - BACKGROUND: Even though the olfactory function usually is improved or unchanged
      after ethmoidectomy, some patients complain of olfactory disturbance, which may
      be caused by direct injury to the olfactory nerves. However, the detailed
      anatomic pathway of the olfactory nerves that leave the olfactory mucosa and
      after going through the cribriform plate insert into the olfactory bulb is
      uncertain. In the studies of lateral nasal wall, we referred to the thin bone
      that connects the middle, superior, and supreme turbinates to the skull base as
      the "conchal plate." We undertook this study to determine the anatomic relation
      between the conchal plate and the olfactory nerve. METHODS: Ten midsagittal
      sections from adult cadaver head specimens were used for gross anatomy and the
      midportion of the conchal plate was taken and fixed in 10% formalin. The
      microscopic structures of the conchal plate were observed after hematoxylin and
      eosin staining. RESULTS: The olfactory nerves originated from the olfactory
      mucosa lining the middle and superior turbinates and ran upward within the bone
      of the conchal plate. These results suggest that the olfactory nerve may be
      injured inadvertently in the conchal plate during ethmoidectomy and that this
      injury is likely to be one of the possible causes of olfactory disturbance.
      CONCLUSION: We propose a possibility that injury to the conchal plate can affect
      olfactory function. Therefore, care should be taken to avoid damage to the
      conchal plate during ethmoidectomy.

PMID- 14599136
TI  - Evaluation of telescopes and forceps for endoscopic transnasal surgery on the
      maxillary sinus.
AB  - BACKGROUND: Contemporary endonasal surgical treatment of chronic hyperplastic
      paranasal sinusitis strives for microsurgical excision of all spots of
      irreversibly diseased hyperplastic mucosa. However, anatomy of the maxillary
      sinus reveals distinct hidden areas and niches that pose problems to optical and
      instrumental control. METHODS: The specific range of view of common telescopes
      (30, 45, and 70 degrees) inside the maxillary sinus after generous middle meatal
      antrostomy is analyzed in three different-sized anatomic specimens. The
      examinations are paralleled by investigations on the range of action of 14
      surgical instruments. The results are visualized by means of a three-dimensional
      computed tomograph of all specimens. RESULTS: The different telescopes and
      surgical tools that are introduced via the middle meatal antrostomy reveal a
      specific overlap in the range of view and in the range of action, respectively.
      Anatomic areas that are difficult to reach e.g., are the medial and anterior
      parts of the sinus and the alveolar recess. An additional inferior antrostomy
      offers minor benefits with respect to control of the prelacrimal recess.
      CONCLUSIONS: Routine surgery on the maxillary sinus in case of chronic
      hyperplastic pansinusitis via middle meatal antrostomy does not cover all hidden
      niches of the sinus. The most important area that is out of sight and control is
      the prelacrimal recess.

PMID- 14599137
TI  - Whether the improvement seen following MIST was due to surgery or a post
      operative DepoMedrol injection.

PMID- 14599138
TI  - Fatigue--a common but often overlooked symptom of rhinosinusitis.

PMID- 14599139
TI  - A simple spectrophotometric method based on pH-indicators for monitoring partial
      and total alkalinity in anaerobic processes.
AB  - Partial alkalinity, as a measure of bicarbonate concentration, and total
      alkalinity, as a measure of the concentration of bicarbonate and volatile fatty
      acids, are useful parameters for monitoring anaerobic digestion processes. This
      paper reports a new method based on pH-indicators and spectrophotometric
      measurements for the monitoring of partial and total alkalinity. The method was
      used in an off-line procedure for monitoring of an anaerobic process and
      displayed less than 5% deviation from the traditional method of measuring partial
      and total alkalinity, as well as being rapid and reproducible. A flow injection
      analysis system based on the method was used on-line for monitoring overload in a
      UASB reactor, which demonstrated changes in alkalinity not easily registered
      using traditional methods.

PMID- 14599140
TI  - Gas emissions and engine behavior when gasoline-alcohol mixtures are used.
AB  - This paper deals with the use of gasoline-methanol and gasoline-ethanol mixtures
      in a small four-stroke engine of internal combustion that is used for the
      movement of a small alternative generator. It was observed that CO and HC
      emissions decrease compared to gasoline when the percentage of methanol, ethanol
      in the fuel was increased, under different load conditions (without load
      conditions and under full electrical load conditions). The use of gasoline
      methanol mixtures showed a higher decrease of emissions. When the mixtures of
      gasoline-70%methanol and gasoline-90%ethanol and 100%ethanol for which the engine
      malfunctioned, the rpm of the engine were not constant and the emissions were
      increased. It is also important that (with the existing regulation of the
      fuel/air ratio that refers to gasoline) the engine functioned for the case of
      gasoline-methanol mixtures up to a concentration of -70%methanol mixture, while
      for the case of gasoline-ethanol mixtures until the use of 100%ethanol.
      Furthermore, during the use of the mixtures of gasoline-methanol and gasoline
      ethanol there was a small increase of fuel consumption when the percentage of the
      methanol or ethanol in the fuel was increased.

PMID- 14599141
TI  - The methane production of poultry slaughtering residues and effects of pre
      treatments on the methane production of poultry feather.
AB  - The biological methane production rate and yield of different poultry
      slaughtering residues were studied. Poultry offal, blood, and bonemeal were rich
      in proteins and lipids and showed high methane yields, 0.7-0.9, 0.5, and 0.6-0.7
      m3 kg(-1) volatile solids(added), respectively (270-340, 100, and 150-170 m3 ton(
      1) wet weight). Blood and bonemeal produced methane rapidly, whereas the methane
      production of offal was more delayed probably due to long-chain fatty acid
      inhibition. The length of delay depended on the source and concentration of
      inoculum and incubation temperature, sewage sludge at 35 degrees C having the
      shortest delay of a few days, while granular sludge did not produce methane
      within 94 days of incubation. Feather showed a somewhat lower methane yield, 0.21
      m3 kg(-1) volatile solids(added) (50 m3 ton(-1) wet weight). Combined thermal
      (120 degrees C, 5 min) and enzymatic (commercial alkaline endopeptidase, 2-10 g
      l(-1)) pre-treatments increased its methane yield by 37 to 51%. Thermal (70-120
      degrees C, 5-60 min), chemical (NaOH 2-10 g l(-1), 2-24 h), and enzymatic pre
      treatments were less effective, with methane yield increasing by 5 to 32%. Based
      on the present results, anaerobic digestion of the studied poultry slaughtering
      residues appears a promising possibility because of the high methane yield and
      nitrogen content of these residues (8 to 14% N of total solids), whereas pre
      treatments were shown to improve the methane production of feather.

PMID- 14599142
TI  - Combined removal of SO2 and NO using sol-gel-derived copper oxide coated alumina
      sorbents/catalysts.
AB  - The present paper reports experimental results on the removal of sulfur dioxide
      and nitrogen oxide from simulated flue gas using a copper oxide coated on alumina
      sorbent/catalyst prepared by the sol-gel method. Selective catalytic reduction of
      nitric oxide by ammonia over sol-gel derived CuO/gamma-Al2O3 sorbents/catalysts
      with different degrees of sulfation was studied in a fixed-bed packed reactor.
      The optimum temperature for NO reduction was found at 350 degrees C for both
      fresh and sulfated catalysts. The properties for simultaneous removal of SO2 and
      NO by the sol-gel-derived CuO/gamma-Al2O3 sorbents were studied using simulated
      dry flue gas. The optimum operating temperature for the combined deSO2/deNO
      operations was identified at 350 degrees C. At the space velocity of 5200 h(-1)
      and 350 degrees C, a fixed-bed reactor packed with the 7.9 wt% CuO/gamma-Al2O3
      sorbent prepared by the sol-gel method offers SO2 sorption capacity of 2.3 mmol
      g(-1) and NO conversion of 92% with a dry simulated flue gas as the feed. Under
      these experimental conditions, the sol-gel derived sorbents/catalysts have
      comparable efficiency for removal of SO2 and NOx as their commercial
      counterparts. The significantly higher crush strength of the sol-gel derived
      sorbents/catalysts make them very promising for their use in the copper oxide
      process for combined removal of SO2 and NOx from flue gas in a single unit
      operation.

PMID- 14599144
TI  - Simultaneous control of metals and organics using a fluidized bed adsorber.
AB  - A previous study has examined the performance of a fluidized activated carbon
      adsorber for removal of organics and particulate emissions from an incinerator
      under various fluidized operating conditions. The results show that it is an
      effective control device to treat the organics and coarse particles. However
      toxic heavy metal compounds cannot be completely destroyed during the
      incineration process and will volatilize at high temperature and then condense to
      form metallic particulates during the cooling of the flue gas. Therefore,
      continuing the previous study, the removal of metals generated from incineration
      by a fluidized bed adsorber at relatively low temperature was performed in the
      current study. Activated carbons with different additives (limestone, aluminum
      oxide and silica sand) were added in the adsorber to remove single metal (Pb, Cr
      and Cd) or mixed metals in the flue gas. Furthermore, an impulse bag house
      integrated after the adsorber and serving as an air pollution control device to
      control the metals and organics simultaneously was also identified. The results
      indicate that different additives can increase the removal efficiency of metals
      from 4% to 24% when the feedstock contains single metal. The integration of the
      fluidized bed adsorber and a bag house was effective to remove the heavy metals,
      organics and particulates in the flue gas.

PMID- 14599143
TI  - Toxicity of heavy metals for microorganisms isolated from slow sand filter
      schmutzdecke.
AB  - This paper describes the susceptibility of three species of environmental
      bacteria isolated from the schmutzdecke of biologically active slow sand filters
      to cadmium, chromium and lead. The microorganisms, all identified as members of
      the genus Pseudomonas, were grown in tryptic soy broth with various
      concentrations of the selected heavy metals. The mean generation times (MGT) of
      the bacteria were compared to evaluate the toxic effects of the heavy metals. All
      three species tolerated high doses of heavy metals and the MGTs increased
      exponentially as the heavy metal concentrations increased; 12 mg l(-1) was the
      highest dose tested and the bacteria continued to grow albeit at very slow rates.
      In dilute media, the toxic effects of heavy metals were enhanced, illustrating
      the protection effect of organic matter and heavy metal complex formation. Growth
      studies of the isolated microorganisms on half-strength tryptic soy agar
      containing 6 mg l(-1) heavy metals also proved useful in determining toxicity.

PMID- 14599145
TI  - Microbial and copper adsorption by smectitic clay--an experimental study.
AB  - The objective of this study was to quantify copper-, bacteria- and bacteriophage
      binding capacities of natural clay with the aim of predicting the adsorption of
      heavy metals, human pathogenic bacteria and viruses by a clayey landfill liner. X
      ray diffraction analysis of six natural clays showed that the dominant phase in
      all deposits consists of smectites together with illite, kaolin and, sometimes,
      palygorskite and sepiolite. The specific surface areas of different clay
      substrates were very high ranging from 293 to 351 m2 g(-1), and indicating a high
      proportion of phyllosilicates, consisting especially of smectites. The physico
      chemical identification of separated smectites showed a high potential adsorbent
      character indicative of a large industrial use. The Kb12 smectite substrate
      chosen arbitrarily among six separated substrates, appeared as an excellent
      copper adsorbent. Copper was adsorbed to clay in a proportion ranging from 94.6
      to 96.0% with an average of 95.1% and its adsorption occurred rapidly in less
      than 30 min. Organic contents of the clay substrate, evaluated as 17% of dry
      mass, may contribute and enhance copper adsorption. Different elution protocols
      using distilled water, 2 and/or 5% nitric acid revealed that while nitric acid
      resulted in the removal of more than 59% of the metal at the lower concentration
      and its complete depletion with a further elution at the higher concentration,
      distilled water alone was unable to remove more than 1% of adsorbed copper. This
      finding suggested that copper ions form high-energy bonds with layer-silicate
      surfaces. Interestingly, the use of a regenerated substrate as copper adsorbent
      subsequent to abundant washings of the used substrate consecutively, with 0.1 N
      HNO3 and distilled water, reduced copper adsorption by approximately 14%,
      suggesting a slight disturbance of clay initial structure. Batch adsorption
      experiments with phage T7 and raw clay Kb12 showed that the tested clay substrate
      appeared as a relatively moderate phage adsorbent since the quantity of adsorbed
      phage averaged 98.2 +/- 0.88% (2 log10 retention) as measured by infectivity for
      Escherichia coli ATCC 11303. As shown by two types of separating procedures,
      natural sedimentation and a low speed centrifugation, bacteriophage particles
      were bound essentially to fine and not to relatively coarse particles of the clay
      suspension. The retention capacity of purified clay Kb12 appeared low, with
      average values lower than 60 and 50%, for Pseudomonas aeruginosa ATCC 15442 and
      Bacillus cereus ATCC 1135, respectively. A significant increase of retention, in
      the order of 30%, was found for both bacteria when the mixture clay-bacteria was
      incubated at laboratory temperature for 6 hours.

PMID- 14599146
TI  - Nitrate removal from drinking water through the use of encapsulated
      microorganisms in alginate beads.
AB  - Biological treatment for removal of nitrate from drinking water is of great
      significance, as traditional physical and chemical methods could not effectively
      remove soluble nitrate. In this report immobilized microorganisms with co
      immobilized calcium tartrate were used for reducing nitrate concentration (110 mg
      l(-1) NO3-N) in a model solution. The carbon source also functions as a
      stabilizing agent for the immobilization matrix. Experiments of denitrification
      showed a high nitrate removal rate while nitrite residual was at a concentration
      higher than expected. The nitrate concentration was reduced to nearly zero (0.2
      1.4 mg l(-1)) after 3 days of operation. The calcium tartrate (4%, w/w) co
      immobilized alginate beads had better nitrate removal performance than tartrate
      in solution. The nitrite-N residual concentration was approximately 1.1-2.9 mg l(
      1) at the end of the experiments, showing the desirability of further
      denitrification. The stability of alginate beads was also tested both to evaluate
      their behaviors and investigate the efficacy of bead recycling. It was found that
      the beads could be used for 8-13 days consecutively without any structural
      deterioration and leaking of microbes.

PMID- 14599147
TI  - Application of electrochemical process for landfill leachate treatment with
      emphasis on heavy metal and organic removal.
AB  - This study was conducted to investigate the mechanisms of electrochemical
      treatment of a landfill leachate with emphasis on lead and organic removal.
      Laboratory electrochemical experiments were conducted using both synthetic
      wastewater and landfill leachate samples. From the synthetic wastewater
      experiments, the lead removal efficiencies were found to be more than 99%. The
      lead removal was observed to be dependent on: the electrical current, ratio
      between reacting surface area and volume of reactor and operation time, and
      following a first-order reaction. Similar results on lead removal were obtained
      when the landfill leachate samples were treated in the electrochemical reactor;
      the percent removal of soluble biological oxygen demand and soluble chemical
      oxygen demand concentrations from the landfill leachate during the
      electrochemical treatment were 30-60%, while the color removal was 70%. The
      sludge generated from the electrochemical reactions using the synthetic lead
      wastewater, analyzed by X-ray diffractometry, was found to be composed mainly of
      maghemite, magnetite, and laurionite. Based on the X-ray fluorescence
      spectrometry analysis, the percent contents of iron and lead were 68.6% as
      maghemite and 10.1% as lead oxide, respectively. The sludge generated from the
      landfill leachate treatment containing lead, analyzed by X-ray diffractometry,
      was found to be composed mainly of maghemite. Based on the X-ray fluorescence
      spectrometry analysis, the percent contents of iron and lead in the sludge were
      69.49% as maghemite and 0.63% as lead oxide, respectively. The sludge volume
      index, capillary suction time and leachability values of the sludge were in
      suitable range for settling, dewatering and disposal.

PMID- 14599148
TI  - Use of a similarity index based on microbial fatty acid (MFA) analysis to monitor
      biological wastewater treatment systems.
AB  - Estimating the stability of microbial community structures may be useful in
      advanced biological wastewater treatment system design and operation. In this
      research, a monitoring method using fatty acid profiles was evaluated for
      detecting changes in microbial community structures. For the evaluation, the
      operating parameters such as pH, organic loading, and chlorine addition were
      varied in two identical laboratory scale conventional activated sludge systems. A
      similarity index based on microbial fatty acid analysis was used to express the
      stability of microbial community structures in the systems. Experiments using a
      model microbial community showed that microbial compositions changed daily even
      under constant operating conditions and that the rate of change increased under
      dynamic operating conditions. Substrate changes brought about a relatively large
      change in a microbial community structure, eventually resulting in a very
      different microbial community. After only 7 days following a substrate change in
      a lab-scale bioreactor, the biomass exhibited only 45% similarity to the original
      structure. The analysis of microbial fatty acids conveys additional information,
      in that it could be used for the calculation of biomass concentrations in a
      wastewater treatment system if microbial fatty acid analyses are executed on a
      routine basis as a monitoring tool for biological wastewater treatment systems.
      The total fatty acid concentrations were about 0.61% of the biomass concentration
      as mixed liquor volatile suspended solid concentrations in this research.

PMID- 14599149
TI  - Monitoring PAH-contaminated soil using laser-induced fluorescence (LIF).
AB  - The heterogeneity and opacity of soil matrices pose considerable challenges for
      the quantification of soil contaminants. In order to investigate the feasibility
      of applying the Laser-Induced Fluorescence technique to measure contamination
      levels of soils, statistical analyses of contaminant levels and intensity of
      fluorescence were investigated in relation to soil properties. A significant
      correlation (R2 > 0.97) between contaminant levels and intensity of fluorescence
      was shown under different matrix conditions, such as moisture content and
      particle size distribution. Higher fluorescence intensities were obtained from
      soils with higher sand and moisture content. The statistical results in relation
      to the interaction between fluorescence intensity and matrix properties rejected
      the hypothesis that all properties of the matrices and contaminants had an equal
      influence on fluorescence. This implied that the concentrations of contaminants
      had the greatest contribution to the fluorescence intensity, but other variables
      also showed a considerable influence.

PMID- 14599150
TI  - Thermal efficiency and environmental performances of a biogas-diesel stationary
      engine.
AB  - Municipal and agricultural waste, and sludge from wastewater treatment represent
      a large source of pollution. Gaseous fuels can be produced from waste
      decomposition and then used to run internal combustion engines for power and heat
      generation. The present paper focuses on thermal efficiency and environmental
      performances of dual-fuel engines fuelled with biogas. Experiments have been
      carried out on a Lister-Petter single cylinder diesel engine, modified for dual
      fuel operation. Natural gas was first used as the primary fuel. An empirical
      correlation was determined to predict the engine load for a given mass flow rate
      for the pilot fuel (diesel) and for the primary fuel (natural gas). That
      correlation has then been tested for three synthesized biogas compositions.
      Computations were performed and the error was estimated to be less than 10%.
      Additionally, NOx and CO2 contents were measured from exhaust gases. Based on
      exhausts gas temperature, the activation energy and the pre-exponential factor of
      an Arrhenius law were then proposed, resulting in a simpler mean to predict NOx.

PMID- 14599151
TI  - Ultraviolet disinfection of effluent from subsurface flow constructed wetlands.
AB  - Subsurface flow constructed wetlands are becoming increasingly common for on-site
      treatment of domestic wastewater. Before spray application, wetland effluent must
      be disinfected. Traditionally, tablet chlorination has been used, but an
      alternative is needed to increase dependability. Consequently, we investigated
      the use of ultraviolet light disinfection of effluent from constructed wetlands.
      Two low pressure (254 nm) and two medium pressure ultraviolet bulbs (190 to 400
      nm) were used for disinfection. Upon installation, all units disinfected effluent
      successfully. After 2 weeks in operation, three of the four units did not reduce
      fecal coliform populations below 200 in 100 ml of effluent due to decreased light
      intensity from films that developed on the bulbs. One unit consistently
      disinfected water to populations lower than 200 in 100 ml for 1 year without
      maintenance. Ultraviolet disinfection, as utilized, was not consistently suitable
      for disinfection of effluent from subsurface flow constructed wetlands because of
      coatings that developed on the bulbs and blocked the light.

PMID- 14599152
TI  - Hydrolysis and acidogenesis of particulate organic material in mesophilic and
      thermophilic anaerobic digestion.
AB  - The purpose of this study was to evaluate the effect of pH and inorganic nutrient
      supplementations for anaerobic hydrolysis and acidogenesis of particulate organic
      materials at both mesophilic (35 degrees C) and thermophilic (55 degrees C)
      temperatures. Hydrolysis and acidogenesis of a synthetic sludge was observed in
      batch operation for the evaluation of the pH effect. pH was uncontrolled in one
      reactor and controlled at 4.5, 5.5, and 6.5 in the other three reactors at both
      temperatures. The greatest degree of hydrolysis and acidogenesis occurred when
      the pH was controlled at 6.5. The pH of the uncontrolled reactor dropped to 3.4
      at both temperatures severely retarding hydrolysis and acidogenesis.
      Concentrations of acetic and n-butyric acids predominated with lower
      concentrations of propionic acid at both temperatures in all reactors. Lactic
      acid was produced as the earliest intermediate but as the reaction proceeded,
      short chain VFAs were produced as final end products with a decrease in lactic
      acid. The higher the pH, the earlier this trend was observed. For the controlled
      reactors at pH 6.5, the soluble COD production and the VSS reduction peaked in 4
      days at 55 degrees C whereas it took about 11 days at 35 degrees C to obtain the
      same result. During the linear SCOD production period at a pH of 6.5 the
      hydrolysis rate of the thermophilic reactor was greater than that for mesophilic.
      Thermophilic conditions appeared to be more sensitive to pH than mesophilic ones
      for both hydrolysis and acidogenesis. Additional experiments were conducted to
      establish the effect of inorganic nutrient (Ca, Fe, Co, and Ni) supplementation
      on hydrolysis and acidogenesis at both temperatures. It has, prior to this, been
      assumed that only methanogenesis benefited from trace metal supplementation.
      However, the results demonstrated the importance of inorganic nutrient
      supplementation to optimize hydrolysis and acidogenesis at both temperatures.

PMID- 14599153
TI  - Health technology assessment: a "must" for laboratory medicine?

PMID- 14599154
TI  - Health technology assessment in clinical biochemistry. Methylmalonic acid: a
      Danish showcase.
AB  - In 1992 plasma methylmalonic acid (MMA) was introduced in Denmark for diagnosing
      vitamin B-12 deficiency. Now, 10 years later, we report on a health technology
      assessment (HTA) suggesting that the clinical usefulness of MMA is uncertain. MMA
      is an obvious component for measurement in the diagnosis of vitamin B-12
      deficiency because MMA accumulates when there is a lack of vitamin B-12, and
      technologically the analysis is of high quality. The diagnostic sensitivity of
      MMA is high, whereas the diagnostic specificity is debatable, and our results
      suggest it to be relatively low. The organizational aspect implies that both MMA
      and P-cobalamins have been increasingly employed, though no consensus on the use
      of the analyses has emerged. The benefit to the patient is not obvious. An
      increased level of MMA does not predict further increases over time, and vitamin
      B-12 treatment shows limited clinical benefit in individuals with a moderately
      increased MMA. The economic consequences of introducing MMA were an increase in
      the costs of MMA and P-cobalamins of 12% per year during 1992-2000 and an
      increase in the turnover of vitamin B-12 preparations of 9% per year. In
      conclusion, MMA was introduced on sound grounds for both pathophysiological
      considerations and analytical quality. Our HTA shows that the resources employed
      to diagnose and to treat vitamin B-12 deficiency have increased considerably, but
      yet we have no evidence to suggest the clinical benefit.

PMID- 14599155
TI  - Health technology assessment and implications for clinical practice: the case of
      prostate cancer screening.
AB  - We describe an initiative to disseminate evidence from systematic reviews about
      the clinical effectiveness of prostate cancer screening to general practitioners
      and urologists in Norway. The Norwegian Centre for Health Technology Assessment
      invited The Norwegian Medical Association, The Norwegian Cancer Society, The
      Norwegian Board of Health, The Norwegian Urological Cancer Group and The
      Norwegian Patient Association to develop and disseminate clinical practice
      recommendations. The clinical effectiveness of prostate cancer screening has been
      assessed in nine independent systematic reviews, which are summarized in a joint
      INAHTA report. The conclusion was that there is no evidence from appropriately
      designed trials that early detection and treatment of prostate cancer can reduce
      mortality, morbidity or improve quality of life. The number of prostate-specific
      antigen (PSA) tests analysed in Norway increased by 47% [corrected] from 1996 to
      1999; at the county level the increase ranged from 12 to 48%. On this background
      we disseminated leaflets with information about PSA and prostate cancer to 4100
      general practitioners and specialists in urology. The main message was, i) PSA
      should not be taken in healthy men, ii) if the test is wanted, the physician is
      obliged to give information about the possible consequences. Despite efforts to
      anchor the information campaign within the mentioned organizations, this met with
      notable opposition from The Norwegian Urological Society. A survey among agencies
      within the INAHTA network showed that more than half of the countries within this
      collaboration have implemented guidelines or recommendations on prostate cancer
      screening. In conclusion, evidence obtained through an international
      collaboration such as the INAHTA collaboration may be used to develop and
      implement national guidelines or recommendations.

PMID- 14599157
TI  - Asymmetric dimethylarginine and total homocysteine in plasma after oral
      methionine loading.
AB  - BACKGROUND: Elevation of homocysteine (Hcy) and asymmetric dimethylarginine
      (ADMA) in plasma are believed to be involved in the pathogenesis of
      cardiovascular disease (CVD). In humans, oral methionine loading results in acute
      elevation of plasma Hcy. This is associated with impaired NO-dependent
      vasodilatation, a mechanism that may explain the relationship between elevated
      Hcy and risk of CVD. ADMA, an endogenous competitive inhibitor of NO-synthase,
      may be elevated in plasma of patients with CVD. It was proposed that ADMA is
      synthesized in a methionine-dependent reaction which also forms Hcy. In this
      study plasma total homocysteine (tHcy) and ADMA concentrations were measured
      before and after oral methionine loading of human subjects. METHODS: Plasma tHcy
      and ADMA levels were measured in 12 healthy males (age 32-58 years) before and
      after oral loading with L-methionine (100 mg/kg body weight in orange juice).
      RESULTS: At noon, 4 h after methionine loading, tHcy and ADMA levels (35.4 +/-
      10.9 and 0.80 +/- 0.13 micromol/L, mean +/- SD) were significantly higher than
      the corresponding values obtained at noon the day before (15.6 +/- 7.4 and 0.63
      +/- 0.10 micromol/L, both p<0.001). Noon values 4 h after methionine loading were
      also significantly higher than values obtained immediately before the methionine
      load (13.7 +/- 5.9 and 0.66 +/- 0.10 micromol/L, both p<0.001). Reinvestigation
      of 8 of 12 subjects showed that at 4 and 8 h after compared with levels
      immediately before methionine loading there was a significant increase in tHcy
      (28.4 +/- 10.2 and 33.45 +/- 11.1 vs. 10.8 +/- 3.3 micromol/L, both p<0.001).
      However, the corresponding ADMA levels did not increase (0.73 +/- 0.17 and 0.76
      +/- 0.22 vs. 0.70 +/- 0.10 micromol/L, both not significant). CONCLUSIONS: No
      clear evidence was found to support the supposition that methionine-induced
      hyperhomocysteinaemia may be accompanied by elevated levels of ADMA, an
      endogenous competitive NO-synthase inhibitor that may represent an alternative
      pathogenic mechanism for homocysteine-associated impairment of endothelial NO
      dependent functions.

PMID- 14599156
TI  - Reasons for Chlamydia trachomatis testing and the associated age-specific
      prevalences.
AB  - OBJECTIVE: to assess the age- and sex-specific prevalence of Chlamydia
      trachomatis infection according to the indications for testing. This was done as
      part of a health technology assessment to identify the populations that would
      benefit most from universal screening, and to identify ongoing potential
      superfluous testing that could liberate resources to be used for targeted
      screening programs. METHODS: In Aarhus County, Denmark, population of 630,000,
      data were collected on 11,423 persons who were being tested for C. trachomatis
      (10,351 females and 1072 males). Indicated on the request slip were: the sex, the
      age and the reasons for testing (infected partner; planned transcervical
      procedure; symptoms consistent with C. trachomatis infection; or routine
      testing). All samples were analyzed by the Ligase Chain Reaction. RESULTS: More
      than 90% of all the tests were conducted in women. The majority of tests were
      performed in the 21-25 years age group but the prevalence was highest in the 16
      20 years age group (7.2%; 95% CI: 5.4%-9.3%). A total of 25% of all tests were
      carried out in asymptomatic women above the age of 30 in whom the prevalence was
      only 1.3% (95% CI: 0.8%-1.9%). More than three times as many women (5.8%) than
      men (1.7%) were tested as sexual partners to C. trachomatis-infected index
      patients but the risk of infection was highest among men. In women who were
      tested prior to a transcervical procedure, the prevalence was highest (5.5%; 95%
      CI: 1.8%-12.4%) in the 16-20 years age group, whereas most samples were obtained
      in women aged 31-35 years in whom the prevalence was only 0.8% (0.2%-2.3%).
      CONCLUSIONS: The prevalence of C. trachomatis infection justifies the screening
      of asymptomatic individuals below 30 years of age. At present, however, 25% of
      all tests are requested in asymptomatic women above the age of 30. It might be
      advisable to use the resources for systematic universal screening of younger
      individuals rather than to continue the current opportunistic screening of older
      women.

PMID- 14599158
TI  - Routine determination of serum methylmalonic acid and plasma total homocysteine
      in Norway.
AB  - OBJECTIVE: To study the total number of combined analyses of methylmalonic acid
      (MMA) and total plasma homocysteine (tHcy) carried out during February 1998 at
      the Central Laboratory of Haukeland University Hospital. METHODS: Laboratory data
      and requester comments of 2917 subjects in whom MMA was requested during February
      1998, were retrieved from the laboratory information system (LIS). In 2520 cases,
      the results from the combined analyses of MMA and tHcy were available. Requester
      comments were registered in the LIS in 1084 cases. Results from additional
      laboratory analyses were accessible in about 10%, of cases. RESULTS: General
      practitioners requested MMA and tHcy on three main indications, i.e. low
      cobalamin, "control" and neurological symptoms. Metabolites were requested in
      twice as many women than men. Furthermore, MMA was requested in younger age
      groups of women compared with men. Plasma tHcy and MMA showed positive
      correlations with age and serum creatinine, and tHcy was generally 1-2 micromol/L
      higher in men than in premenopausal women. In cobalamin- (serum cobalamin > 300
      pmol/L) and/or folate- (serum folate > 10 nmol/L) replete subjects, the average
      difference in MMA or tHcy according to the highest and lowest creatinine
      quartiles was 0.08 and 5-6 micromol/L, respectively. Different combinations of
      MMA and tHcy were evaluated by using a 5 x 5 matrix of predefined concentration
      intervals. Based on this matrix, cobalamin and folate deficiency could be
      excluded or the likely diagnoses proposed in 76% of cases. Cobalamin deficiency
      or folate deficiency was likely in about 7% and 12% of the subjects investigated,
      respectively. CONCLUSIONS: A combined analysis of MMA and tHcy provides
      complementary diagnostic information. When interpreting MMA and tHcy values, age,
      gender and renal function in particular must be taken into account. Typical
      combinations of MMA and tHcy concentration intervals could be proposed, which
      could either exclude deficiency or indicate likely diagnoses and/or influence of
      confounders.

PMID- 14599159
TI  - Prerequisites for establishing general recommendations for diagnosis and
      treatment of vitamin B12 deficiency and cost-utility evaluation of these
      guidelines.
AB  - There is currently no consensus on how to define, diagnose and treat vitamin B12
      deficiency. This is partly due to insufficient and non-uniform study design. It
      is essential to come to a harmonization of rational study designs. In order to
      evaluate new tests for the diagnosis of vitamin B12 deficiency, it is important
      that independent and unequivocal criteria for a clear-cut definition of the
      disease are used. Furthermore, it is crucial to have a mutual understanding on
      the progression of the disease, how fast the different symptoms may develop and
      on the expected time frame of treatment and evaluation of response. The kind and
      intensity of treatment must also be agreed upon. The present article overviews
      the potential strategies of how to define and diagnose vitamin B12 deficiency and
      on follow-up of treatment response. Finally, based on these considerations, the
      prerequisites of a cost-utility analysis of guidelines for diagnosing vitamin B12
      deficiency are discussed.

PMID- 14599160
TI  - Ex vivo magnetic resonance imaging of the distal row of equine carpal bones:
      assessment of bone sclerosis and cartilage damage.
AB  - The distal row of carpal bones (C2, C3, and C4) from eight left intercarpal
      joints--four from Standardbred Trotters and four from Swedish Warmblood horses-
      were used to assess the potential of magnetic resonance (MR) imaging to detect
      cartilage and bone lesions. The joints used in the study were classified by
      macroscopic and radiographic examinations as having normal, mild, moderate, or
      severe articular cartilage lesions and bone sclerosis. Those classifications
      correlated well with the appearance of the MR images. Bone sclerosis in the MR
      images was observed as regions of decreased signal intensity. Upon quantitative
      analysis of the MR images there was a significant difference (p < 0.0001) in the
      MR signal intensity from areas where radiographic bone sclerosis was observed
      compared to areas of radiographic nonsclerotic bone. In addition, the MR images
      were used to pilot the location of histology slices through areas of interest
      that were then examined microscopically; hence, the lesions found from the MR
      imaging examination were verified microscopically. It was concluded that
      cartilage lesions and cartilage loss are related to the sclerotic state of the
      underlying bone. The MR protocols developed in this study were applied on five
      intact cadaveric carpal joints, and it was concluded that MR imaging could
      successfully be used in the intact joint to detect minor cartilage and bone
      lesions not visualized by either radiography or macroscopic examination. Hence,
      MR imaging can be used to delineate interactions between articular cartilage and
      subchondral bone over time and in vivo.

PMID- 14599161
TI  - Use of intraoperative mesenteric portovenography in congenital portosystemic
      shunt surgery.
AB  - A retrospective study of the use of intraoperative mesenteric portovenography
      (IOMP) in the surgical management of congenital portosystemic shunts in 100 dogs
      and cats was performed. Each portovenogram was scored using a subjective visual
      analogue scale (VAS) and was assessed for the presence of portal atresia or
      hypoplasia. VAS scores and portal hypoplasia assessments were obtained for
      portovenogram images obtained for each animal both before shunt manipulation
      (preligation) and following the temporary, complete ligation of the vessel
      (postligation). In each patient, surgical records were reviewed to ascertain the
      degree of shunt attenuation that was achieved at surgery. Hepatic portal
      vasculature was significantly different on postligation compared with preligation
      IOMP. Sixty-two percent of animals had apparent portal hypoplasia or atresia on
      their preligation IOMP. The majority of these (81%) had an improvement in portal
      vasculature on postligation IOMP. It was concluded that both preligation and
      postligation IOMP provided valuable information regarding the morphology of
      congenital portosystemic shunts. An accurate assessment of an animal's portal
      vasculature could only be made following the interpretation of a postligation
      portovenogram, and these findings significantly influenced the surgical
      management of the patient. Although individuals with high postligation VAS scores
      were more likely to achieve full shunt attenuation at surgery, there was no
      quantifiable relationship between IOMP findings and the degree of shunt
      attenuation achieved.

PMID- 14599162
TI  - Magnetic resonance imaging in the diagnosis of lymphoma involving the brachial
      plexus in a cat.
AB  - An 11-year-old, neutered, female Domestic Long Hair cat had a 3-week history of
      left forelimb lameness. Conscious proprioception and postural reflexes were
      absent on the left thoracic limb. The cat had slightly reduced placing and
      hopping responses on the left pelvic limb, absent cutaneous trunci muscle reflex
      on the left side, and left triceps muscle atrophy. Magnetic resonance imaging
      revealed a 2 x 2 x 2 cm mass in the region of the left brachial plexus. The cat
      was treated by left forelimb amputation and hemilaminectomy. Histopathology of
      the brachial plexus revealed lymphoma.

PMID- 14599164
TI  - Computed tomographic appearance of choanal atresia in an alpaca cria.
AB  - A 6-hour-old alpaca cria was admitted for evaluation of respiratory distress
      since birth. Contrast radiography confirmed the presence of bilateral choanal
      atresia, and computed tomography (CT) evaluation was planned to aid in the
      surgical treatment. Due to deterioration in the cria's condition, euthanasia was
      performed prior to the CT examination. Postmortem CT examination was performed to
      determine the appearance of choanal atresia. The embryology and CT appearance of
      choanal atresia is discussed.

PMID- 14599163
TI  - Radiographic anatomy of the canine coxofemoral joint using the dorsal acetabular
      rim (DAR) view.
AB  - A radiographic study of the anatomy of the canine acetabulum was performed. The
      relationship between the area of dorsal acetabular rim that is subject to early
      damage in dogs with coxofemoral joint laxity, and the "DAR point" identified on
      dorsal acetabular rim (DAR) radiographic views was examined. Radiographs and
      digital photographs were made of the pelvis harvested from each of six skeletally
      mature dogs. Through analysis of these images, it was determined that in the
      standing animal, the DAR point is located 4-6 mm (or approximately 37 degrees)
      caudal to the dorsal acetabular rim area that is prone to early damage in dogs
      with coxofemoral joint laxity. This study suggests that the DAR radiographic view
      may under-represent changes to the dorsal acetabular rim in dogs with coxofemoral
      laxity.

PMID- 14599166
TI  - High field strength (4.7T) magnetic resonance imaging of hydrocephalus in an
      African Grey parrot (Psittacus erithacus).
AB  - Hydrocephalus was diagnosed in a juvenile African Grey parrot by high-field
      strength (4.7-Tesla) magnetic resonance imaging (MRI). Excellent anatomic detail
      was achieved, and there was severe dilation of all ventricles. Relative
      obstruction was localized to the level of or beyond the outflow of the fourth
      ventricle. There have been several reports of hydrocephalus diagnosed postmortem
      in psittacines (i.e., hook-billed parrots), however, this is the first report of
      an antemortem diagnosis in a psittacine using high-field strength MRI.

PMID- 14599165
TI  - Imaging of a spinal nephroblastoma in a dog.
AB  - An 8-month-old German Shepherd dog was presented for investigation of pelvic limb
      gait abnormality. Neurolocalization indicated a T3-L3 spinal cord lesion. The
      myelographic appearance was of an intramedullary lesion at T9/10, but upon
      subsequent magnetic resonance imaging it was determined that the mass was
      extramedullary. A diagnosis of nephroblastoma was made on histological
      examination. The imaging features of this rare tumor and the differentiation of
      intradural-extramedullary and intramedullary masses are discussed.

PMID- 14599167
TI  - Radiographic gastrointestinal contrast study in the ostrich (Struthio camelus).
AB  - Ten gastrointestinal contrast studies were performed with barium on seven
      clinically healthy ostriches. Concentrations of 25-100% w/vol liquid barium
      sulfate at 7 and 10 ml/kg were administered by stomach tube after withholding
      food for 16 h. A 6-frame technique for left-to-right lateral views in standing
      and a 3-frame technique for the dorsoventral views in sternally recumbent adult
      ostriches were used for survey and contrast radiographs. Objectives were to
      describe the appearance of the normal gastrointestinal tract with contrast
      radiography and to provide a guideline for optimal dosage and concentration of
      barium sulfate as well as a reliable protocol for frequency of radiographs.
      Structures that were consistently identified included the esophagus,
      proventriculus, ventriculus, duodenum, jejunum, proximal, and distal rectum. Due
      to the superimposition of the remainder of the small intestine, individual
      components were difficult to differentiate. The caeca were inconsistently
      highlighted and only for a short time. The ventral pouch of the coprodeum never
      filled with contrast medium.

PMID- 14599168
TI  - Imaging diagnosis: the abdominal air-vasculogram in a dog with splenic torsion
      and clostridial infection.

PMID- 14599170
TI  - Ultrasonographic and pathologic features of intestinal smooth muscle hypertrophy
      in four cats.
AB  - The ultrasonographic findings for four cats with intestinal smooth muscle
      hypertrophy are described. In two cats, intestinal smooth muscle hypertrophy was
      associated with chronic enteritis. In the remaining two cats, intestinal smooth
      muscle hypertrophy affected the intestinal tract proximal to stenosis due to
      alimentary lymphoma and an intestinal foreign body, respectively. Moderate
      increased thickness of the affected intestinal wall, measuring 7-8 mm, was
      evident on abdominal ultrasonographic examination of all subjects. In addition,
      the ultrasonographic five-layered feature of the intestinal wall was maintained,
      and only the muscular layer appeared thickened. Abdominal ultrasound allowed a
      presumptive diagnosis of intestinal smooth muscle hypertrophy that was confirmed
      histologically in all cats.

PMID- 14599169
TI  - Ultrasonographic findings in dogs and cats with gastrointestinal perforation.
AB  - A retrospective study was performed to evaluate the sonographic features of
      gastrointestinal (GI) perforation in dogs and cats. Sonographic findings in 19
      animals (14 dogs and 5 cats) included regional bright mesenteric fat (19),
      peritoneal effusion (16), fluid-filled stomach or intestines (12), GI wall
      thickening (11), presence of free air (9), loss of GI wall layering (9), regional
      lymphadenopathy (8), reduced GI motility (7), pancreatic changes (4), corrugated
      intestines (4), presence of a mass (3), presence of a foreign body (3), and
      mineralization of the gastric wall (1). In 14 patients, "perforation" was listed
      as a differential diagnosis by the sonographer. Abdominal radiographs and
      radiographic reports were available for 14 patients. Radiographic findings were
      decreased serosal detail (12), free air (8), peritoneal contrast medium (1), and
      suspected foreign body (1). GI perforation was listed as radiographic diagnosis
      in eight patients, seven of which had evidence of pneumoperitoneum, and one had
      leakage of contrast material on an upper GI study. In 9/14 patients with
      radiography, "GI perforation" was listed as a sonographic diagnosis. In three
      patients in which free air was diagnosed sonographically, radiographs were either
      not available (2) or the presence of free air was not detected at presentation
      (1). Peritoneal fluid analysis was performed in nine patients, five of which were
      identified as septic inflammation, and the remaining four were classified as
      neutrophilic inflammation with no etiologic agent identified. The histologic or
      surgical diagnoses were as follows: three intestinal surgical dehiscence; one
      percutaneous endoscopic gastrostomy tube site leakage; one duodenal
      adenocarcinoma; one ileocolic lymphoma; one trichobezoar; one ascarid impaction;
      and one bobby pin foreign body. In the remaining 10 patients, a focal area of
      gastric/intestinal ulceration or transmural necrosis with perforation was
      identified without evidence of an underlying cause.

PMID- 14599171
TI  - Diagnostic value of ultrasonography in differentiating enteritis from intestinal
      neoplasia in dogs.
AB  - One hundred and fifty dogs with histopathologically confirmed intestinal disease
      were evaluated retrospectively. Sixty-one dogs had enteritis and 89 dogs had
      intestinal neoplasia. Ultrasonographic findings including the thickness and
      distribution of the intestinal lesion, the integrity of intestinal wall layering,
      regional lymph node thickness, the location of the intestinal segment involved,
      and regional motility were evaluated. Dogs with intestinal tumor had wall
      thickness (1.5 cm) significantly greater than dogs with NSE lesions (0.6 cm; p <
      0.001). Ninety-nine percent of dogs with intestinal tumor had loss of wall
      layering while 88% of dogs with NSE had normal or altered wall layering (p <
      0.001). Dogs with NSE were significantly more likely to have diffuse lesion (72%)
      than dogs with intestinal tumor (2%; p < 0.001). Lymph node median thickness in
      24/61 dogs with NSE was 1.00 cm. The median thickness of the lymph nodes in 56/89
      dogs with intestinal tumors was 1.9 cm. A multivariate analysis showed that loss
      of wall layering alone was an excellent predictive factor in differentiating
      intestinal tumor from NSE. In our population, dogs with loss of intestinal wall
      layering were 50.9 times more likely to have a tumor than enteritis.

PMID- 14599172
TI  - Ultrasound evaluation of small bowel thickness compared to weight in normal dogs.
AB  - The use of ultrasound to measure small bowel thickness is an important part of
      any ultrasound examination of the abdomen. Increased thickness of the intestinal
      wall is a hallmark for the detection of diseases ranging from inflammatory bowel
      disease to neoplasia. Our subjective impression has been that dogs with no
      clinical signs of gastrointestinal disease often have sonographic measurements
      greater than published norms. The purpose of this study was to prospectively
      reevaluate these norms. The clinical history on all dogs receiving an abdominal
      ultrasound examination was evaluated for signs of gastrointestinal disease. Those
      without clinical signs were entered into this study. The documentation of body
      weight, breed, jejunal thickness, and duodenal thickness was made in 231 dogs.
      Dogs were placed into five groups based on their weight. Sixty-nine breeds were
      represented with weight ranging from 2.1 to 64 kg. A statistically significant (P
      < or = 0.05) correlation between body weight and both jejunal and duodenal
      thickness was observed. We also found that the maximum thickness in both jejunum
      and duodenum in healthy dogs was larger than previously reported. These data
      indicate norms for the jejunum of < or = 4.1 mm for dogs up to 20 kg, < or = 4.4
      mm for dogs between 20 and 39.9 kg, and < or = 4.7 mm for dogs over 40 kg. The
      data indicate norms for the duodenum < or = 5.1 mm for dogs up to 20 kg, < or =
      5.3 kg for dogs between 20 and 29.9 kg, and < or = 6.0 mm for dogs over 30 kg.

PMID- 14599173
TI  - Cerebral ventricular size in developing normal kittens measured by
      ultrasonography.
AB  - To evaluate the age of fontanelle closure of normal kittens and the size of their
      lateral ventricles, 50 ultrasonographic examinations using the bregmatic
      fontanelle as an acoustic window were made. Seven kittens, laboratory animals,
      were included in the study. To verify the location of the lateral ventricle, two
      of the kittens were sacrificed as neonates. In one of them ink was injected prior
      to autopsy into one lateral ventricle under sonographic guidance. In a
      longitudinal study of five of the kittens, the skull depth and the depth of the
      central part of the lateral ventricle reproduced in a longitudinal view could be
      measured up to the age of about 5 months. During that period, the skull depth
      increased from a median value of 1.95 cm (1.92-1.98) in a seven-day-old cat to
      2.58 cm (2.52-2.59) in a 154-day-old cat, while the afore-mentioned ventricle
      values increased from 0.3 mm to 1.1 mm.

PMID- 14599174
TI  - Prenatal sonographic diagnosis of fetal death and hydranencephaly in two
      Chihuahua fetuses.
AB  - Hydranencephaly and fetal death was diagnosed in two of three fetuses during the
      abdominal sonographic examination of a 2.5-year-old, intact female Chihuahua that
      had clinical signs of dystocia 63 days after mating. A cesarean section was
      performed and one live normal puppy was present. Two dead puppies, each with a
      markedly enlarged and fluid filled skull were removed.

PMID- 14599175
TI  - Images in medicine. The haunted brain.

PMID- 14599176
TI  - The development of a facile tandem Wolff/Cope rearrangement for the synthesis of
      fused carbocyclic skeletons.
AB  - A set of mild processes for the conversion of vinyl cyclopropyl diazo ketones to
      highly functionalized cycloheptadienones and vinyl cyclopentenones by use of a
      target-inspired tandem Wolff/Cope rearrangement sequence is described. A
      divergent reaction course of the vinyl cyclopropyl diazo ketone substrates under
      sono- or photochemical activation provides good to excellent yields (55-98%) of
      the product cycloheptadienones and vinyl cyclopentenones.

PMID- 14599177
TI  - High-frequency dynamic nuclear polarization in MAS spectra of membrane and
      soluble proteins.
AB  - One of the principal promises of solid-state NMR (SSNMR) magic angle spinning
      (MAS) experiments has been the possibility of determining the structures of
      molecules in states that are not accessible via X-ray or solution NMR experiments
      e.g., membrane or amyloid proteins. However, the low sensitivity of SSNMR often
      restricts structural studies to small-model compounds and precludes many higher
      dimensional solid-state MAS experiments on such systems. To address the
      sensitivity problem, we have developed experiments that utilize dynamic nuclear
      polarization (DNP) to enhance sensitivity. In this communication, we report the
      successful application of MAS DNP to samples of cryoprotected soluble and
      membrane proteins. In particular, we have observed DNP signal enhancements of up
      to 50 in 15N MAS spectra of bacteriorhodopsin (bR) and alpha-lytic protease
      (alpha-LP). The spectra were recorded at approximately 90 K where MAS is
      experimentally straightforward, and the results suggest that the described
      protocol will be widely applicable.

PMID- 14599178
TI  - Luotonin A. A naturally occurring human DNA topoisomerase I poison.
AB  - Luotonin A is a pyrroloquinazolinoquinoline alkaloid isolated from the Chinese
      herbal medicinal plant Peganum nigellastrum. Although previously shown to exhibit
      cytotoxicity against the murine leukemia P-388 cell line, the mechanism of action
      of luotonin A is unknown. Presently, we demonstrate that luotonin A stabilizes
      the human DNA topoisomerase I-DNA covalent binary complex, affording the same
      pattern of cleavage as the structurally related topoisomerase I inhibitor
      camptothecin. Luotonin A also mediated topoisomerase I-dependent cytotoxicity
      toward Saccharyomyces cerevisiae lacking yeast topoisomerase I, but harboring a
      plasmid having the human topoisomerase I gene under the control of a galactose
      promoter. This finding identifies a putative biochemical locus for the cytotoxic
      action of luotonin A and has important implications for the mechanism of action
      of camptothecin and the design of camptothecin analogues.

PMID- 14599180
TI  - Asymmetric Simmons-Smith cyclopropanation of unfunctionalized olefins.
AB  - This paper describes a promising asymmetric cyclopropanation system for
      unfunctionalized olefins using readily available dipeptide N-Boc-l-Val-l-Pro-OMe
      as ligand.

PMID- 14599179
TI  - Bioactive recognition sites may not be energetically preferred in protein
      carbohydrate complexes in the gas phase.
AB  - Arrhenius parameters, obtained with the blackbody infrared radiative dissociation
      technique, are reported for the dissociation of a gaseous protonated complex of
      an antibody single chain fragment and its native trisaccharide antigen
      originating from nonspecific interactions during the nanoelectrospray process. It
      is shown that the nonspecific complex is kinetically more stable and, at the +10
      charge state, energetically more stable than the corresponding specific complex
      originating from interactions in solution. This is the first demonstration that a
      bioactive recognition site is not energetically preferred in a protein-ligand
      complex in the gas phase.

PMID- 14599181
TI  - Synthesis of the elusive (R3P)2MF2 (M = Pd, Pt) complexes.
AB  - The synthesis and characterization of previously unknown palladium(II) and
      platinum(II) difluoro phosphine complexes are described. These complexes can be
      obtained either via a halide metathesis reaction with AgF in dichloromethane or
      by reacting the corresponding dimethyl complexes with XeF2. While the Pt(II)
      complexes can be prepared with both aryl- and alkyl-phosphine ligands, the
      stability of the Pd(II) complexes is limited to those having cis-oriented
      trialkyl phosphine ligands.

PMID- 14599183
TI  - Selective complexation of Li+ in water at neutral pH using a self-assembled
      ionophore.
AB  - A trinuclear metallamacrocycle was obtained by assembly of a tridentate ligand
      and a ruthenium complex in water at neutral pH. The complex acts as a potent
      ionophore for lithium ions with a Li+/Na+ selectivity of 10 000:1.

PMID- 14599182
TI  - Clean inversion of configuration in the Pd-catalyzed cross-coupling of 2-bromo
      1,3-dienes.
AB  - The Pd-catalyzed cross-coupling reaction of 2-bromo-1,3-dienes derived from alkyl
      aldehydes, especially with Cl2Pd(DPEphos) as a catalyst, proceeds with clean
      stereoinversion of the Br-bearing C=C bond to produce in high yields and in high
      stereoselectivity (>/=97-98%) conjugated Z,E dienes of potentially high utility
      in the synthesis of complex natural products. The observed stereoinversion cannot
      be readily accommodated by the widely accepted pi-sigma-pi rearrangement
      mechanism for isomerization of ordinary allylpalladium derivatives.

PMID- 14599184
TI  - Catalytic hydrosilylation of alkenes by a ruthenium silylene complex. Evidence
      for a new hydrosilylation mechanism.
AB  - Novel ruthenium and osmium silylene species containing Si-H bonds have been
      synthesized and characterized by NMR spectroscopy. The ruthenium complex
      [Cp*(iPr3P)(H)2Ru=Si(H)Ph.Et2O][B(C6F5)4] catalyzes the hydrosilyation of alkenes
      with excellent substrate selectivity for primary silanes and exclusive anti
      Markovnikov regiochemistry. Evidence for a novel mechanism involving direct
      addition of an alkene to the silylene Si-H bond is presented.

PMID- 14599185
TI  - The first applications of carbene ligands in cross-couplings of alkyl
      electrophiles: sonogashira reactions of unactivated alkyl bromides and iodides.
AB  - A Pd/N-heterocyclic carbene-based catalyst achieves the Sonogashira coupling of
      an array of functionalized, beta-hydrogen-containing alkyl bromides and iodides
      under mild conditions. By furnishing the first example of a nonphosphine-based
      palladium catalyst for cross-coupling unactivated alkyl electrophiles, this study
      provides an impetus for future efforts at catalyst development that extend beyond
      phosphine ligands.

PMID- 14599186
TI  - Distinct thermodynamics for the formation and cleavage of N-H bonds in aniline
      and ammonia. Directly-observed reductive elimination of ammonia from an isolated
      amido hydride complex.
AB  - The reactions of aryl and alkylamines with the (PCP)Ir fragment (PCP = 1,3-di
      tert-butylphosphinobenzene) were studied to determine the reactivities and
      stabilities of amine and amido hydride complexes relative to C-H activation
      products. Reaction of aniline with the (PCP)Ir unit generated from (PCP)IrH2 and
      norbornene resulted in the N-H oxidative addition product (PhNH)(H)Ir(PCP) (1a).
      In contrast, reaction of this fragment with ammonia gave the ammonia complex
      (NH3)Ir(PCP) (2). The amido hydride complex that would be formed by oxidative
      addition of ammonia, (PCP)Ir(NH2)(H) (1b), was generated independently by
      deprotonation of the ammonia complex (NH3)Ir(H)(Cl)(PCP) (3) with KN(SiMe3)2 at
      low temperature. This amido hydride complex underwent reductive elimination at
      room temperature to form the ammonia complex 2. Addition of CO to anilide complex
      1a gave (PCP)Ir(PhNH)(H)(CO) (4a). Addition of CNtBu to terminal amido complex 1b
      formed (PCP)Ir(NH2)(H)(CNtBu) (4b), the first structurally characterized iridium
      amido hydride. Complexes 4a and 4b underwent reductive elimination of aniline and
      ammonia; parent amido complex 4b reacted faster than anilide 4a. These
      observations suggest distinct thermodynamics for the formation and cleavage of N
      H bonds in aniline and ammonia. Complexes 1a, 2, 4a, and 4b were characterized by
      single-crystal X-ray diffraction methods.

PMID- 14599187
TI  - Calix[2]bipyrrole[2]furan and calix[2]bipyrrole[2]thiophene: new pyrrolic
      receptors exhibiting a preference for carboxylate anions.
AB  - Heterocycles other than pyrrole, specifically bipyrrole, furan, and thiophene,
      have been used to construct two new, calixpyrrole-like anion receptors; binding
      studies, carried out by ITC in CH3CN, reveal a selectivity for "Y-shaped" anions,
      such as benzoate, over spherical ones, such as chloride.

PMID- 14599188
TI  - [60]Fullerene-containing polyurethane films with large ultrafast nonresonant
      third-order nonlinearity at telecommunication wavelengths.
AB  - A significantly enhanced, ultrafast third-order optical nonlinearity at the
      wavelengths of 1150-1600 nm was demonstrated with cross-linked C60-containing
      polyurethane films using the Z-scan technique. Good-quality polymer films with a
      high loading of C60 derivative were obtained by cross-linking of the hydroxyl
      containing C60 derivative and a triisocyanate. The positive Kerr coefficient with
      nonresonant nonlinear refractive index n2 falls in the range of (3.7 +/- 0.80) x
      10-4 to (2.0 +/- 0.6) x 10-3 cm2/GW, and the calculated chi(3) and gamma values
      are up to 9.7 x 10-11 and 9.6 x 10-32 esu at 1550 nm, which are several orders of
      enhancement in third-order optical nonlinearity over pristine C60 in solution and
      1-2 orders of enhancement over recently reported C60 derivatives and conjugated
      polymers.

PMID- 14599190
TI  - One-step water-assisted synthesis of high-quality carbon nanotubes directly from
      graphite.
AB  - At 1 atm pressure, high-quality multiwall carbon nanotubes were synthesized
      directly from graphite in the absence of catalyst by a one-step water-assisted
      method.

PMID- 14599189
TI  - Relationship between redox function and protein stability of cytochromes c.
AB  - Electrochemical, 1H NMR, and optical studies on mesophile Pseudomonas aeruginosa
      cytochrome c551, its single (F34Y) and quintuple (F7A/V13M/F34Y/E43Y/V78I)
      mutants, and thermophile Hydrogenobacter thermophilus cytochrome c552 at wide
      temperature range demonstrated that the stable protein exhibits the low redox
      potential predominantly due to the enthalpic contribution to the redox reaction.
      The overall stability of the oxidized form was shown to determine the stability
      of the Fe-methionine coordination bond, which then directly regulates the redox
      function.

PMID- 14599191
TI  - Control of a double helix DNA assembly by use of cross-linked oligonucleotides.
AB  - Disulfide cross-linked oligonucleotides for connecting two DNA double helixes
      have been designed, synthesized, and characterized. Employing these cross-linked
      oligonucleotides, two double helixes can be arranged side by side, and the
      orientations can be controlled both in parallel and antiparallel ways by addition
      of a specific complementary DNA strand.

PMID- 14599192
TI  - High electron mobility in ladder polymer field-effect transistors.
AB  - Field-effect mobility of electrons as high as 0.1 cm2/(V s) is observed in n
      channel thin film transistors fabricated from a solution spin-coated conjugated
      ladder polymer, poly(benzobisimidazobenzophenanthroline) (BBL), under ambient air
      conditions. This is the highest electron mobility observed to date in a
      conjugated polymer semiconductor. Comparative studies of n-channel thin film
      transistors made from a structurally similar nonladder conjugated polymer BBB
      gave an electron mobility of 10-6 cm2/(V s). These results demonstrate that
      electron transport can be as facile as hole transport in conjugated polymer
      semiconductors and that ladder architecture of a conjugated polymer can
      substantially enhance charge carrier mobility.

PMID- 14599194
TI  - The glass transition time scale and configurational entropy in polymers: an
      experimental molecular view.
AB  - We report direct experimental observation of local conformational dynamics in a
      polymer chain at the calorimetric glass transition temperature Tg. Variable
      temperature two-dimensional (2D) solid-state exchange NMR, at natural abundance,
      reveals segmental dynamics in pure polyisobutylene (PIB) occurring on a time
      scale of several seconds over the Tg range observed by DSC (203-208 K). To our
      knowledge, this is the first direct observation of molecular-level conformer
      interchange (trans-trans/trans-gauche/gauche-gauche) at the caloric glass
      transition temperature. Our results provide a chronologically accurate and
      pedagogically advantageous demonstration of molecular processes during a polymer
      phase transition, relative to traditional bulk mechanical and calorimetric
      techniques. More importantly, we use a miscible blend to demonstrate a general
      strategy for quantitative evaluation of configurational entropy changes via
      combination of temperature-dependent 2D exchange NMR and Adams-Gibbs theory. Our
      results on the Tg time scale are directly relevant to fundamental understanding
      of the Tg length scale, i.e., the dimension of cooperatively rearranging regions.

PMID- 14599193
TI  - Mapping the sites for selective oxidation of guanines in DNA.
AB  - The effective energy of a positive charge when it is localized at a specific
      guanine nucleobase in DNA was calculated using density functional theory. The
      results demonstrate that the efficiency of a guanine to act as a hole-trap in DNA
      strongly depends on the nature of the flanking nucleobases. The presence of a
      pyrimidine base at the 3' position adjacent to a guanine significantly increases
      the localization energy of the positive charge. The calculated distributions of a
      positive charge in sequences of two or three adjacent guanines, flanked by other
      nucleobases, provide an explanation for experimental literature data on the site
      selective oxidation of DNA.

PMID- 14599195
TI  - Bis-silicon-bridged stilbene homologues synthesized by new intramolecular
      reductive double cyclization.
AB  - A homologous series of bis-silicon-bridged stilbenes has been synthesized on the
      basis of a new intramolecular reductive cyclization of bis(o-silyl)
      diphenylacetylene. Thus, the reaction of bis(o-silyl)-diphenylacetylenes with
      excess lithium naphthalenide undergoes the two-electron reduction at the
      acetylene moiety to produce a dianion intermediate, which further undergoes a
      double cyclization in a 5-exo mode to produce the bis-silicon-bridged stilbenes.
      This methodology can also be applied to the synthesis of tetrakis-silicon-bridged
      bis(styryl)benzenes. The silicon-bridged pi-conjugated systems thus prepared show
      intense fluorescence in the visible region. Comparison of a bis-silicon-bridged
      stilbene with its carbon analogue demonstrates the substantial effects of the
      silicon-bridges on the electronic structures and thus on the fluorescence
      properties.

PMID- 14599196
TI  - A Switch for the transfer of substrate between nonribosomal peptide and
      polyketide modules of the rifamycin synthetase assembly line.
AB  - A nonribosomal peptide synthetase (NRPS) loading module and a polyketide synthase
      (PKS) elongation module catalyze the preliminary steps in the biosynthesis of the
      rifamycin antibiotics. A benzoate molecule is covalently attached to the
      phosphopantetheine arm of the thiolation domain of the loading module when its
      reaction partner methylmalonyl-CoA is absent. Occupancy of the thiolation domain
      of the elongation module by a methylmalonyl moiety appears to trigger
      intermodular transfer of benzoate to the ketosynthase domain of the elongation
      module. This transthiolation event is fast relative to the initial loading of
      benzoate onto the loading module. It will be of interest to determine if these
      results are generally true for intermodular acyl transfer in other NRPS-PKS and
      PKS assembly lines.

PMID- 14599197
TI  - Discovery of the archaeal chemical link between glycogen (starch) synthase
      families using a new mass spectrometry assay.
AB  - Starch and its analogue glycogen are biosynthesized by enzymes that have been
      classified by sequence similarities into two families that have no significant
      sequence overlap: the animal/fungal glycogen synthases and the plant/bacterial
      glycogen (starch) synthases. Recent gene sequence analysis of putative archaea
      enzymes implicates them as a third family that links the structural and
      functional features of the other two classes. Herein, we present the first rapid
      electrospray ionization mass spectrometry-based assay to quantify any
      carbohydrate-polymerizing activity, the first cloning and recombinant expression
      as well as verification of the putative function of a glycogen synthase from the
      hyperthermophilic archaea Pyrococcus furiosus, and the characterization of a
      variety of glycogen synthases with the new assay. The new assay allowed the
      determination of Km and Vmax values for the rabbit, yeast, and P. furiosus
      glycogen synthases. Most surprisingly, unlike the synthases from rabbit or yeast
      and in contradiction to what would be expected from structural studies of other
      nucleotide-sugar binding proteins, the synthase from the archaea source accepts
      both uridine- and adenine-diphosphate activated glucose competitively and with
      comparable affinities to form a glucose polymer. This loose substrate specificity
      implicates this protein as the chemical link between the two branches of glycogen
      synthases that have evolved to accept primarily one or the other nucleotide as
      well as a good source enzyme for polymer bioengineering efforts.

PMID- 14599198
TI  - Density functional theory studies of electron interaction with DNA: can zero eV
      electrons induce strand breaks?
AB  - The discovery of DNA strand breaks induced by low energy secondary electrons
      sparks a necessity to elucidate the mechanism. Through theoretical studies based
      on a sugar-phosphate-sugar model that mimics a backbone section of the DNA
      strand, it is found that bond cleavages at 3' or 5'C-O sites after addition of an
      electron are possible with a ca. 10 kcal/mol activation barrier. Moreover, the
      potential energy surfaces show that dissociation at both sites is highly
      favorable thermodynamically. Although the phosphate group in DNA is not a favored
      site for electron attachment because of competitive electron transfer to the
      bases, any electrons which attach to phosphates on first encounter may induce
      strand breaks even when the electron energy is near zero eV. These findings have
      profound implication as low energy secondary electrons are abundantly generated
      in all types of ionization radiation.

PMID- 14599199
TI  - Robust mixed 10/12 helices promoted by "alternating chirality" in a new family of
      C-linked carbo-beta-peptides.
AB  - The C-linked carbo-beta-peptides, oligomers of a new class of C-linked carbo
      beta3-amino acids, have been shown to generate mixed 12/10 and 10/12 helices. The
      design involves use of "alternating chirality" of the epimeric (at the amine
      center) monomers to control the stability of these helices. The observation of
      stable 12/10 helix in a tripeptide and 10/12 helix in a tetrapeptide is
      unprecedented.

PMID- 14599200
TI  - The crystal structures of the chiral alkyllithium bases [n-BuLi.(-)-sparteine]2
      and [Et2O.(i-PrLi)2.(-)-sparteine].
AB  - The crystal structures of the two chiral alkyllithium bases [n-BuLi.(-)
      sparteine]2 (1) and [Et2O.(i-PrLi)2.(-)-sparteine] (2) have been determined. For
      compound 1, a symmetric dimer is observed in the solid state, with two (-)
      sparteine ligands coordinating to the lithium centers. Because of steric reasons,
      compound 2 crystallizes as an unsymmetric dimer with the four methyl groups
      pointing away from the sterically demanding (-)-sparteine ligand. Compound 2
      contains one four-coordinate lithium center [coordinated to (-)-sparteine] and
      one three-coordinate lithium center (coordinated to Et2O). As a result of this
      arrangement, significantly different Li-C distances are found in the central four
      membered ring of compound 2.

PMID- 14599201
TI  - The organization and assembly of a beta-sheet formed by a prion peptide in
      solution: an isotope-edited FTIR study.
AB  - Insight into the details of protein misfolding diseases requires a detailed
      understanding of the conformation and dynamics of multistrand beta-sheet
      aggregates. Here, we report an isotope-edited FTIR study of a model peptide
      directed at the elucidation of residue-level details of the structure and
      mechanism of a beta-sheet aggregate. A series of specifically isotope-labeled
      derivatives of a short peptide (H1) derived from residues 109 through 122 of the
      prion protein PrPC have been synthesized and characterized by FTIR. On the basis
      of the analysis of variable temperature FTIR spectra of these peptides in
      solution, the organization of strands within the beta-sheets has been determined;
      at equilibrium, the strands form a beta-sheet in which the hydrophobic core (112
      122) participates in the sheet structure, resulting in the alignment of residue
      117 in all of the strands. The peptides initially form a kinetically trapped
      intermediate beta-sheet, with a distribution of strand alignments, which can be
      rearranged into the stable equilibrium conformation by an annealing cycle. These
      observations are discussed in terms of the biological significance of residue 117
      of the prion protein and the mechanism of beta-aggregate nucleation in prion
      proteins.

PMID- 14599202
TI  - Magnetic properties of tetrakis[4-(alpha-diazobenzyl)pyridine]bis(thiocyanato
      N)cobalt(II) in frozen solution after irradiation. Formation of a single-molecule
      magnet in frozen solution.
AB  - Magnetic properties after irradiation of a 1:4 mixture of Co(SCN)2 and 4-(alpha
      diazobenzyl)pyridine in frozen solution were investigated by ac and dc
      magneto/susceptometry. Observations of the frequency dependence of chi'' signals
      and of a hysteresis loop at 2 K in ac and dc measurements, respectively, indicate
      that the generated cobalt-carbene complex functions as a single-molecule magnet.
      This is the first example of a monometallic single-molecule magnet of nanometer
      size.

PMID- 14599203
TI  - A novel mechanism of proton transfer in protonated peptides.
AB  - The study presents quantum-chemical calculations on proton transfer in protonated
      N-acetylglycyl-N1-methylglycinamide (AGA) as a short oligopeptide model. All
      calculations employ the B3LYP functional and the 6-31++G** basis set. Two
      different mechanisms of proton transfer are discussed. The rate-determining step
      of the first mechanism exhibits an energy barrier of about 17.7 kcal mol-1, and
      it is represented by an isomerization of the proton around the double bond of the
      carbonyl group. The second mechanism is based on the large conformational
      flexibility of AGA, where all carbonyl oxygens cooperate. The rate-determining
      step of this mechanism exhibits an energy barrier of only 8.3 kcal mol-1.

PMID- 14599204
TI  - Supramolecular hydrogels respond to ligand-receptor interaction.
AB  - N-(Fluorenyl-9-Methoxycarbonyl) dipeptides form supramolecular hydrogels via
      hydrogen bonding and hydrophobic interactions. These hydrogels respond to a
      ligand-receptor interaction as well as to thermal or pH perturbation and also
      exhibit chiral recognition.

PMID- 14599205
TI  - Substrate-induced pairing in 2,3,6,7,10,11-hexakis-undecalkoxy-triphenylene self
      assembled monolayers on Au111.
AB  - We present an STM study of self-assembled monolayers of 2,3,6,7,10,11-undecalkoxy
      substituted triphenylene (T11) at the n-tetradecane/Au(111) interface under
      ambient conditions. T11 molecules self-organize as paired rows with molecules
      lying flat on the surface in an antiparallel position. Three alkyl chains of each
      T11 molecule align along the 110 direction of the underlying Au(111) substrate.
      The association of T11 in molecular pairs appears to result from a substrate
      induced mechanism governed by the strong anisotropic interaction between T11
      alkyl chains and Au(111).

PMID- 14599206
TI  - Tunable photochromism of spirooxazines via metal coordination.
AB  - Through the incorporation of a phenanthroline ligand into the oxazine moiety of
      photochromic spirooxazines, a series of photochromic spirooxazine-phenanthroline
      metal complexes have been synthesized, resulting in tunable and significantly
      increased photoresponsivities. Such systems are of interest for the investigation
      of multifunctional photochromic materials. These novel metal complexes retain
      their photochromic activity in the complexed state, leading to ligand binding in
      both the spirooxazine and the photomerocyanine forms during the photoconversion.
      A significant stabilization of the photomerocyanine form results from metal
      complexation, as indicated by the shift in thermal equilibrium values (KT = 0.06)
      upon metal complexation (KT = 0.6-1.2). Photoconversion occurs with first-order
      kinetics, suggesting the absence of an intermediate state. A third
      photostationary state is observed in these systems induced by visible irradiation
      of the thermal equilibrium state, leading to a three-state system. This new class
      of compounds provides the opportunity to investigate the synergy between changes
      in electronic structure associated with photoisomerization, and metal-centered
      functionality.

PMID- 14599207
TI  - Electrocatalytic investigation of light-induced electron transfer between
      cytochrome c6 and photosystem I.
AB  - A light-activated electron-transfer chain was assembled using solubilized
      cyanobacterial photosystem I as photoactive enzyme, cytochrome c(6) (also from
      cyanobacteria) as electron donor, and methyl viologen as electron acceptor. The
      photocatalytic activity of the ensemble was measured by direct and reversible
      electrochemistry of cytochrome c(6) at a surface-modified gold electrode.
      Analysis of the electrochemical response with an appropriate model for the
      reaction mechanism allowed the relation of the overall catalytic reaction rate to
      the individual steps of the catalytic cycle. Second-order rate constants were
      determined for the first time under steady-state conditions. The results validate
      this approach as an efficient method for the study of electron transfer between
      photoactive enzymes and their redox partners.

PMID- 14599208
TI  - Competitive reactions in solutions of poly-L-histidine, calf thymus DNA, and
      synthetic polyanions: determining the binding constants of polyelectrolytes.
AB  - The physicochemical characteristics of a nonviral gene delivery system will
      govern its functional bioactivity; however, empiricism dominates the literature
      in this field, and a significant deficiency of quantitative investigation and
      evaluation of nonviral gene delivery vehicles remains. Herein, we derive a
      physical model and experimental method to quantitatively determine the binding
      constants between a model polycationic nonviral gene delivery vehicle poly-L
      histidine (PLH) and calf thymus DNA. The approach has utility to a variety of
      systems and is not limited to the described polymer model. The interaction of PLH
      with DNA was monitored by fluorescence quenching of an ethidium bromide probe in
      the pH range 4 to 8. The interaction increased with pH decrease with the most
      pronounced change between pH 6 and 7. The obtained pH-dependence of fraction of
      salt bonds formed between PLH and DNA was used to estimate pK(a) of PLH in the
      presence of DNA, which equaled 6.24. The interaction of PLH with DNA in the
      presence of added synthetic polyanions was studied by the same approach and found
      to be controlled by pH, nature of the charge groups of the polyanion, and its
      degree of polymerization. In the mixture with sodium poly(styrenesulfonate) the
      interaction was negligible in the whole studied pH range, whereas in the mixtures
      with sodium poly(acrylate) (PA) or sodium poly(methacrylate), DNA was able to
      compete effectively for the binding with PLH. For PA samples with degree of
      polymerization higher than degree of polymerization of PLH, DP(PA) > DP(PLH), the
      fraction of polycation bound to DNA was constant regardless of DP(PA.) In
      contrast, at DP(PA) < DP(PLH), a pronounced increase in the bound fraction was
      observed. It substantiates the notion that the binding energy of two polymers is
      mainly controlled by the DP of the shorter component of polyelectrolyte complex.
      The data on PLH distribution between DNA and added polyanion with different
      values of DP were treated according to the developed procedure to yield the
      effective binding constants of PLH with DNA and polyanion-competitor, calculated
      both per mole of interacting units K(1) and mole of interacting chains K(n). In
      all cases, K(1) had similar numerical values reflecting common type of
      interaction stabilizing the complexes, i.e., electrostatics. Slight variation of
      K(1) yielded in drastic changes in K(n) and alteration of dominance of PLH
      interaction with DNA or synthetic polyanion. The results of the study can have a
      high impact in deriving the correlation between the binding constant of a
      polycation to DNA and its ability to serve as gene delivery vehicle.

PMID- 14599209
TI  - Free radical reactions of methionine in peptides: mechanisms relevant to beta
      amyloid oxidation and Alzheimer's disease.
AB  - The pathogenesis of Alzheimer's disease is strongly associated with the formation
      and deposition of beta-amyloid peptide (beta AP) in the brain. This peptide
      contains a methionine (Met) residue in the C-terminal domain, which is important
      for its neurotoxicity and its propensity to reduce transition metals and to form
      reactive oxygen species. Theoretical studies have proposed the formation of beta
      AP Met radical cations as intermediates, but no experimental evidence with regard
      to formation and reactivity of these species in beta AP is available, largely due
      to the insolubility of the peptide. To define the potential reactions of Met
      radical cations in beta AP, we have performed time-resolved UV spectroscopic and
      conductivity studies with small model peptides, which show for the first time
      that (i) Met radical cations in peptides can be stabilized through bond formation
      with either the oxygen or the nitrogen atoms of adjacent peptide bonds; (ii) the
      formation of sulfur-oxygen bonds is kinetically preferred, but on longer time
      scales, sulfur-oxygen bonds convert into sulfur-nitrogen bonds in a pH-dependent
      manner; and (iii) ultimately, sulfur-nitrogen bonded radicals may transform
      intramolecularly into carbon-centered radicals located on the (alpha)C moiety of
      the peptide backbone.

PMID- 14599210
TI  - Resonance Raman spectroscopic studies of hydroperoxo-myoglobin at cryogenic
      temperatures.
AB  - In agreement with previous reports (Gasyna, Z. FEBS Lett. 1979, 106, 213-218 and
      Leibl, W.; Nitschke, W.; Huettermann, J. Biochim. Biophys. Acta 1986, 870, 20-30)
      radiolytically reduced samples of oxygenated myoglobin at cryogenic temperatures
      have been shown by optical absorption and EPR studies to produce directly the
      peroxo-bound myoglobin at 77 K. Annealing to temperatures near 185 K induces
      proton transfer, resulting in the formation of the hydroperoxo heme derivative.
      Resonance Raman studies of the annealed samples has permitted, for the first
      time, the direct observation of the key nu(Fe-O) stretching mode of the
      physiologically important Fe-OOH fragment of this ubiquitous intermediate. The
      assignment of this mode to a feature appearing at 617 cm(-1) is strongly
      supported by documentation of a 25 cm(-1) shift to lower energy upon substitution
      with (18)O(2) and by a 5 cm(-1) shift to lower energy for samples prepared in
      solutions of deuterated solvent.

PMID- 14599211
TI  - Hypochlorite-mediated fragmentation of hyaluronan, chondroitin sulfates, and
      related N-acetyl glycosamines: evidence for chloramide intermediates, free
      radical transfer reactions, and site-specific fragmentation.
AB  - Myeloperoxidase released from activated phagocytes reacts with H(2)O(2) in the
      presence of chloride ions to give hypochlorous acid. This oxidant has been
      implicated in the fragmentation of glycosaminoglycans, such as hyaluronan and
      chondroitin sulfates. In this study it is shown that reaction of HOCl with
      glycosaminoglycans and model compounds yields chloramides derived from the N
      acetyl function of the glycosamine rings. The results of EPR spin trapping and
      product studies are consistent with the formation of amidyl radicals from these
      chloramides via both metal ion-dependent and -independent processes. In the case
      of glycosaminoglycan-derived amidyl radicals, evidence has been obtained in
      studies with model glycosides that these radicals undergo rapid intramolecular
      abstraction reactions to give carbon-centered radicals at C-2 on the N-acetyl
      glycosamine rings (via a 1,2-hydrogen atom shift) and at C-4 on the neighboring
      uronic acid residues (via 1,5-hydrogen atom shifts). The C-4 carbon-centered
      radicals, and analogous species derived from model glycosides, undergo pH
      independent beta-scission reactions that result in glycosidic bond cleavage. With
      N-acetyl glucosamine C-1 alkyl glycosides, product formation via this mechanism
      is near quantitative with respect to chloramide loss. Analogous reactions with
      the glycosaminoglycans result in selective fragmentation at disaccharide
      intervals, as evidenced by the formation of "ladders" on gels; this selectivity
      is less marked under atmospheric oxygen concentrations than under anoxic
      conditions, due to competing peroxyl radical reactions. As the extracellular
      matrix plays a key role in mediating cell adhesion, growth, activation, and
      signaling, such HOCl-mediated glycosaminoglycan fragmentation may play a key role
      in disease progression and resolution, with the resulting fragments modulating
      the magnitude and quality of the immune response in inflammatory conditions.

PMID- 14599213
TI  - Impressive structural diversity and polymorphism in the modular compounds ABi3Q5
      (A = Rb, Cs; Q = S, Se, Te).
AB  - An outstanding example of structural diversity and complexity is found in the
      compounds with the general formula ABi(3)Q(5) (A = alkali metal; Q = chalcogen).
      gamma-RbBi(3)S(5) (I), alpha-RbBi(3)Se(5) (II), beta-RbBi(3)Se(5) (III), gamma
      RbBi(3)Se(5) (IV), CsBi(3)Se(5) (V), RbBi(3)Se(4)Te (VI), and RbBi(3)Se(3)Te(2)
      (VII) were synthesized from A(2)Q (A = Rb, Cs; Q = S, Se) and Bi(2)Q(3) (Q = S,
      Se or Te) at temperatures above 650 degrees C using appropriate reaction
      protocols. gamma-RbBi(3)S(5) and alpha-RbBi(3)Se(5) have three-dimensional tunnel
      structures while the rest of the compounds have lamellar structures. gamma
      RbBi(3)S(5), gamma-RbBi(3)Se(5), and its isostructural analogues RbBi(3)Se(4)Te
      and RbBi(3)Se(3)Te(2) crystallize in the orthorhombic space group Pnma with a =
      11.744(2) A, b = 4.0519(5) A, c = 21.081(3) A, R1 = 2.9%, wR2 = 6.3% for (I), a =
      21.956(7) A, b = 4.136(2) A, c = 12.357(4) A, R1 = 6.2%, wR2 = 13.5% for (IV),
      and a = 22.018(3) A, b = 4.2217(6) A, c = 12.614(2) A, R1 = 6.2%, wR2 = 10.3% for
      (VI). gamma-RbBi(3)S(5) has a three-dimensional tunnel structure that differs
      from the Se analogues. alpha-RbBi(3)Se(5) crystallizes in the monoclinic space
      group C2/m with a = 36.779(4) A, b = 4.1480(5) A, c = 25.363(3) A, beta =
      120.403(2) degrees, R1 = 4.9%, wR2 = 9.9%. beta-RbBi(3)Se(5) and isostructural
      CsBi(3)Se(5) adopt the space group P2(1)/m with a = 13.537(2) A, b = 4.1431(6) A,
      c = 21.545(3) A, beta = 91.297(3) degrees, R1 = 4.9%, wR2 = 11.0% for (III) and a
      = 13.603(3) A, b = 4.1502(8) A, c = 21.639(4) A, beta = 91.435(3) degrees, R1 =
      6.1%, wR2 = 13.4% for (V). alpha-RbBi(3)Se(5) is also three-dimensional, whereas
      beta-RbBi(3)Se(5) and CsBi(3)Se(5) have stepped layers with alkali metal ions
      found disordered in several trigonal prismatic sites between the layers. In gamma
      RbBi(3)Se(5) and RbBi(3)Se(4)Te, the layers consist of Bi(2)Te(3)-type fragments,
      which are connected in a stepwise manner. In the mixed Se/Te analogue, the Te
      occupies the chalcogen sites that are on the "surface" of the layers. All
      compounds are narrow band-gap semiconductors with optical band gaps ranging 0.4
      1.0 eV. The thermal stability of all phases was studied, and it was determined
      that gamma-RbBi(3)Se(5) is more stable than the and alpha- and beta-forms.
      Electronic band calculations at the density functional theory (DFT) level
      performed on alpha-, beta-, and gamma-RbBi(3)Se(5) support the presence of
      indirect band gaps and were used to assess their relative thermodynamic
      stability.

PMID- 14599212
TI  - Eutectic phase polymerization of activated ribonucleotide mixtures yields quasi
      equimolar incorporation of purine and pyrimidine nucleobases.
AB  - The RNA world hypothesis requires a plausible mechanism by which RNA itself (or
      precursor RNA-like polymers) can be synthesized nonenzymatically from the
      corresponding building blocks. Simulation experiments have exploited chemically
      reactive mononucleotides as monomers. Solutions of such monomers in the prebiotic
      environment were likely to be very dilute, but in experimental simulations of
      polymerization reactions dilute solutions of activated mononucleotides in the
      millimolar range hydrolyze extensively, and only trace amounts of dimers and
      trimers are formed. We report here that random medium-size RNA analogues with
      mixed sequences (5- to 17-mers with traces of longer products) can be synthesized
      in ice eutectic phases that are produced when dilute solutions of activated
      monomers and catalysts (Mg(II) and Pb(II)) are frozen and maintained at -18
      degrees C for periods up to 38 days. Under these conditions, the monomers are
      concentrated as eutectics in an ice matrix. Hydrolysis of the activated
      mononucleotides was suppressed at low-temperature ranges, and polymerization was
      enhanced with yields up to 90%. Analysis of the mixed oligomers established that
      incorporation of both purine and pyrimidine bases proceeded at comparable rates
      and yields. These results suggest that ice deposits on the early Earth could have
      facilitated the synthesis of short- and medium-size random sequence RNA analogues
      and thereby provided a microenvironment suitable for the formation of biopolymers
      or their precursors.

PMID- 14599214
TI  - Combinatorial decoding: an approach for universal DNA array fabrication.
AB  - A fiber optic microsphere-based oligonucleotide array is described that employs
      the sequence of the oligonucleotide probe attached to each microsphere as
      positional identifiers. Each microsphere serves as an immobilized array feature,
      functionalized with a unique single-stranded oligonucleotide sequence and
      randomly distributed into an array of microwells. To determine the sequences
      attached to individual microspheres, a series of fluorescently labeled
      combinatorial-pooled oligonucleotide target solutions was designed. Each
      combinatorial decoding solution is intended to identify the nucleotide at a
      particular position on every microsphere in the array. The combinatorial target
      solutions were synthesized by linking the four possible nucleotides at each
      position to four different fluorescent reporter dyes. As such, when the solutions
      were hybridized to the array, one of four possible fluorescent responses was
      generated for each position on a microsphere probe sequence. Adjusting the
      stringency of hybridization enabled single-base mismatch discrimination, and the
      signal with the highest intensity corresponded to the perfect nucleotide match.
      By consecutively exposing the array to a series of combinatorial decoding pool
      solutions, it was possible to simultaneously determine the sequence of every
      randomly positioned oligonucleotide-functionalized microsphere in the array. Once
      mapped, the microsphere array can be used for any typical genomic microarray
      experiment.

PMID- 14599215
TI  - Ground-state conformational equilibrium and photochemical behavior of syn and
      anti N,N'-dimethyl-N,N'-di-1-naphthylurea protophanes.
AB  - The structure, spectroscopy, and photochemistry of N,N'-dimethyl-N,N'-di-1
      naphthylurea have been investigated and compared to the properties of the
      corresponding secondary diarylurea N,N'-di-1-naphthylurea and the tertiary mono
      arylurea N,N,N'-trimethyl-N'-1-naphthylurea. The crystal structures and solution
      NMR spectra of the tertiary and secondary dinaphthylureas establish that they
      adopt folded (E,E) and extended (Z,Z) structures, respectively, both in the solid
      state and in solution. In solution, the tertiary E,E-dinaphthylurea exists as a
      mixture of syn and anti conformations separated by a barrier of ca. 14 kcal/mol,
      as determined by variable-temperature (1)H NMR spectroscopy. Computational
      exploration of the ground-state potential energy surface suggests that the lowest
      energy pathway for interconversion of the syn and anti conformers requires
      concurrent rotation about both the nitrogen-naphthalene and the nitrogen-carbonyl
      single bonds. The tertiary dinaphthylurea exhibits blue-shifted absorption and
      red-shifted emission attributed to excitonic interactions between the naphthalene
      rings. The secondary dinaphthylureas and mono naphthylurea have typical
      naphthalene-like monomer absorption and fluorescence spectra. Dual exponential
      fluorescence decay is assigned to the two conformers of the tertiary
      dinaphthylurea. Nonlinear fitting of the fluorescence decay times provides
      activation parameters for singlet decay of the two conformers. The decay process
      is attributed to nonsynchronous naphthalene-naphthalene bonding which, in the
      case of the syn conformer, results in the formation of a [2+2] intramolecular
      adduct. The preferred E,E conformation and moderate barrier to conformational
      isomerization make the tertiary dinaphthylurea an attractive building block for
      larger self-organizing pi-stacked aromatic arrays.

PMID- 14599216
TI  - The effect of the initial water of hydration on the energetics, structures, and
      H/D exchange mechanism of a family of pentapeptides: an experimental and
      theoretical study.
AB  - A series of gas-phase experiments and extensive theoretical modeling was done on
      the family of singly protonated peptides AARAA, Ac-AARAA, and AARAA-OMe.
      (AARAA)H(+) underwent extensive H/D exchange with D(2)O, whereas the other two
      peptides with blocked termini did not, implying that a salt bridge was involved
      in the H/D exchange process. Ion mobility measurements and complementary
      molecular modeling unambiguously identified the 300 K structures of all three
      protonated peptides as charge solvation structures, not salt bridges. High-level
      density functional theory calculations indicated the global minimum of
      (AARAA)H(+) was a charge solvation structure with the lowest-energy salt bridge
      structure 4.8 kcal/mol higher in energy. Uptake of the first five water molecules
      of hydration at 260 K showed near identical propensities for all three peptides
      consistent with a common structural motif. Quantitative measurements of Delta H
      degrees and Delta S degrees for the first two waters of hydration were very
      similar for all three peptides, again suggestive of a common structure. A
      detailed search of the potential energy surface for the singly hydrated
      (AARAA)H(+) using molecular mechanics and density functional theory approaches
      indicated a charge solvation structure was the global minimum, but now the lowest
      energy salt bridge structure was only 1.8 kcal/mol higher in energy. Importantly,
      a low-energy transition state connecting the charge solvation and the salt bridge
      structures was found where the D(2)O molecule facilitated H/D exchange via the
      relay mechanism. This "relay" transition state was 7 kcal/mol below the
      (AARAA)H(+) + D(2)O asymptotic energy, suggesting that facile H/D exchange could
      occur in this system. There was no equivalent low-lying relay mechanism
      transition state for the (Ac-AARAA)H(+) and (AARAA-OMe)H(+) peptides, consistent
      with the fact that H/D exchange was not observed. Hence, the combined
      experimental and theoretical methods confirmed that a salt bridge was involved in
      the H/D exchange by D(2)O of (AARAA)H(+), but it existed only as a kinetic
      intermediate, not as a global minimum structure. These findings suggest that
      caution must be observed in drawing structural conclusions from H/D exchange
      only. A prescription is given here for understanding both the structural and H/D
      exchange mechanistic aspects of bare and singly hydrated peptides.

PMID- 14599217
TI  - "Electromers" of the tetramethyleneethane radical cation and their nonexistence
      in the octamethyl derivative: interplay of experiment and theory.
AB  - Bicyclopropylidene 1a and its octamethyl derivative 1b are subjected to
      ionization by X-irradiation in solid argon. In accord with previous experiments,
      this treatment leads to the spontaneous opening of both cyclopropylidene rings,
      as does ionization of 1b by gamma-irradiation in CFCl(3) at 77 K. The resulting
      tetramethyleneethane (or bisallyl) radical cations 2a+* and 2b+* are
      distinguished by a broad band in the NIR. In the case of 2a+*, wavelength
      selective photolyses reveal the presence of two interconvertible species with
      very similar yet distinct spectra. Based on DFT and CASSCF/CASPT2 calculations,
      these spectra are assigned to two "electromeric" forms of 2a+* which differ in
      the nature of the singly occupied MO. The NIR bands correspond to charge
      resonance transitions between states with fully delocalized spin and charge.
      Calculations predict that similar electromers should also exist in 2b+* which
      shows a much weaker NIR band, but no corresponding experimental evidence could be
      found. On the other hand, the ESR spectrum of 2b+* indicates that, in contrast to
      2a+*, the spin is largely localized in one of the two allylic moieties in 2b+*.
      Although no theoretical method is presently available that would permit an
      accurate modeling of the opposing factors favoring localized or delocalized
      structures in molecules such as 2a+* or 2b+*, the observed trends can be
      satisfactorily rationalized on the basis of semiquantitative considerations. In
      particular, the important role of vibronic coupling in shaping the potential
      surfaces for such systems is emphasized.

PMID- 14599219
TI  - Novel "Potentially antiaromatic", acidichromic quinonediimines with tunable
      delocalization of their 6 pi-electron subunits.
AB  - We present a novel family of "potentially antiaromatic" alkyl-substituted p
      benzoquinonediimine pH-dependent chromophores. It appears from the structural
      data that these overall 12 pi-electron molecules should be better considered as
      constituted by two chemically connected but electronically not conjugated 6 pi
      electron subunits. Molecule 5 appears to be the first example of two separated,
      conjugated, and localized 6 pi-electron systems that can be tuned by reversible
      protonation to become delocalized. The mono- and diprotonated derivatives have
      been characterized by spectroscopic methods and X-ray diffraction. These systems
      develop supramolecular interactions in the solid state that clearly reflect the
      degree of protonation and depend on the nature of the counterion. These compounds
      constitute new chromophores for which the color can be tuned depending on the
      degree of protonation, going in solution from yellow for 5 to red for 5.HCl and
      blue for 5.2HCl. Theoretical calculations have provided a deeper insight into the
      electronic structure of these molecules and allowed an assignment of the
      experimental UV-vis spectra. The visible and near-UV spectrum of the neutral and
      protonated benzoquinonediimines can be classically assigned from the coupling of
      two 6 pi-electron polymethine units. TD-DFT calculations confirm the observed red
      shift of the two lowest pi --> pi* transitions of the benzoquinonediimines upon
      protonation and relate it to the moderate energy lowering of the HOMO --> LUMO
      transition induced by the delocalization of the polymethine pi system.

PMID- 14599218
TI  - Application of conformation design in acyclic stereoselection: total synthesis of
      borrelidin as the crystalline benzene solvate.
AB  - The total synthesis of (-)-borrelidin (treponemycin), a structurally distinct 18
      membered macrolide antibiotic, has been achieved. It was isolated as the
      crystalline benzene solvate, and its structure was confirmed by a single-crystal
      X-ray analysis. The deoxypropionate subunit consisting of four alternating C
      methyl groups with a C(4)-C(10) syn/syn/anti orientation was elaborated by a new
      method of iterative cuprate additions to acyclic alpha,beta-unsaturated esters
      relying on two consecutive 1,3-inductions and starting with d-glyceraldehyde as
      the chiral progenitor. The unique Z/E cyanodiene unit was obtained as a single
      isomer by application of the Still-Gennari olefination protocol. The gamma
      hydroxycyclopentane carboxylic acid subunit was prepared from L-malic acid
      utilizing a sequential introduction of C-vinyl and C-allyl groups, capitalizing
      on 1,2-induction in an acyclic alpha,beta-unsaturated ester and carbocyclization
      by a Grubbs ring closure metathesis reaction. The prevalence of 1,3-syn-disposed
      deoxypropionate triads in the cuprate additions is rationalized on the basis of
      minimized syn-pentane interactions in the transition states. A virtual diamond
      lattice was used as a visual tool to portray the low-energy conformations of the
      acyclic substrates, and corroborated by (1)H NMR homodecoupling studies.

PMID- 14599221
TI  - Crucial role of three-center hydrogen bonding in a challenging chiral molecular
      recognition.
AB  - The enantio-discrimination of beta-chiral primary ammonium ions is achieved by a
      rational approach that utilizes three-center (bifurcated) hydrogen bonding. The
      extraction experiments on various selected guests reveal that the bifurcated H
      bonding plays a crucial role for the chiral discrimination. The X-ray data
      obtained for an inclusion complex substantiate such interactions. Using the
      bifurcated H-bonding, the chiral molecular recognition with our C(3)-symmetric
      tripodal oxazoline receptors is extended generally toward ammonium ions of alpha
      , beta-, and alpha,beta-chiral amines. Simple molecular models, evoking the
      bifurcated H-bonding, explain the chiral discrimination modes.

PMID- 14599220
TI  - Myoglobin-CO substate structures and dynamics: multidimensional vibrational
      echoes and molecular dynamics simulations.
AB  - Spectrally resolved infrared stimulated vibrational echo data were obtained for
      sperm whale carbonmonoxymyoglobin (MbCO) at 300 K. The measured dephasing
      dynamics of the CO ligand are in agreement with dephasing dynamics calculated
      with molecular dynamics (MD) simulations for MbCO with the residue histidine-64
      (His64) having its imidazole epsilon nitrogen protonated (N(epsilon)-H). The two
      conformational substate structures B(epsilon) and R(epsilon) observed in the MD
      simulations are assigned to the spectroscopic A(1) and A(3) conformational
      substates of MbCO, respectively, based on the agreement between the
      experimentally measured and calculated dephasing dynamics for these substates. In
      the A(1) substate, the N(epsilon)-H proton and N(delta) of His64 are
      approximately equidistant from the CO ligand, while in the A(3) substate, the
      N(epsilon)-H of His64 is oriented toward the CO, and the N(delta) is on the
      surface of the protein. The MD simulations show that dynamics of His64 represent
      the major source of vibrational dephasing of the CO ligand in the A(3) state on
      both femtosecond and picosecond time scales. Dephasing in the A(1) state is
      controlled by His64 on femtosecond time scales, and by the rest of the protein
      and the water solvent on longer time scales.

PMID- 14599222
TI  - Intramolecular 1,3-dipolar ene reactions of nitrile oxides occur by stepwise 1,1
      cycloaddition/retro-ene mechanisms.
AB  - Density functional theory studies of intramolecular ene-like (or the so-called
      1,3-dipolar ene) reactions between nitrile oxides and alkenes (Ishikawa, T.;
      Urano, J.; Ikeda, S.; Kobayashi, Y.; Saito, S. Angew. Chem., Int. Ed. 2002, 41,
      1586) show that this reaction is a three-step process involving a stepwise
      carbenoid addition of nitrile oxide to form a bicyclic nitroso compound, followed
      by a retro-ene reaction of the nitrosocyclopropane intermediate. The competitive
      reactions, either the intramolecular (3+2) reactions between nitrile oxides and
      alkenes or the intermolecular dimerizations of nitrile oxides to form furoxans,
      can overwhelm the intramolecular 1,3-dipolar ene reactions when the tether
      joining the nitrile oxide and alkene is elongated or some substituents such as
      trimethylsilyl are absent.

PMID- 14599223
TI  - Comparative reactivity of sterically crowded nf3 (C5Me5)3Nd and (C5Me5)3U
      complexes with CO: formation of a nonclassical carbonium ion versus an f element
      metal carbonyl complex.
AB  - Sterically crowded isoelectronic nf(3) (C(5)Me(5))(3)M complexes of neodymium and
      uranium, compounds which have unconventionally long metal ligand distances, are
      found to react very differently with CO as a substrate. The 4f(3) complex
      (C(5)Me(5))(3)Nd reacts with CO to form a nonclassical carbonium ion complex,
      (C(5)Me(5))(2)Nd(O(2)C(7)Me(5)), which contains a three-coordinate planar carbon.
      (C(5)Me(5))(3)U reacts with CO to form an even more crowded CO adduct through a
      reaction type never observed before for (C(5)Me(5))(3)M compounds. The rare
      uranium carbonyl complex, (C(5)Me(5))(3)U(CO), has nu(CO) = 1922 cm(-1) and a U
      C(CO) distance of 2.485(9) A.

PMID- 14599225
TI  - Influence of a polar near-neighbor on incipient proton transfer in a strongly
      hydrogen bonded complex.
AB  - Rotational spectroscopy and ab initio calculations have been used to characterize
      the complexes H(3)N-HF and H(3)N-HF-HF in the gas phase. H(3)N-HF is a C(3v)
      symmetric, hydrogen bonded system with an NF distance of 2.640(21) A and an N...H
      hydrogen bond length of 1.693(42) A. The H(3)N-HF-HF complex, on the other hand,
      forms a six-membered HN-HF-HF ring, in which both the linear hydrogen bond in the
      H(3)N-HF moiety and the F-H-F angle of (HF)(2) are perturbed relative to those in
      the corresponding dimers. The N...F and F...F distances in the trimer are
      2.4509(74) A and 2.651(11) A, respectively. The N...H hydrogen bond length in
      H(3)N-HF-HF is 1.488(12) A, a value which is 0.205(54) A shorter than that in
      H(3)N-HF. Similarly, the F...F distance, 2.651(11) A, is 0.13(2) A shorter than
      that in (HF)(2). Counterpoise-corrected geometry optimizations are presented,
      which are in good agreement with the experimental structures for both the dimer
      and trimer, and further characterize small, but significant, changes in the NH(3)
      and HF subunits upon complexation. Analysis of internal rotation in the spectrum
      of H(3)N-HF-HF gives the potential barrier for internal rotation of the NH(3)
      unit, V(3), to be 118(2) cm(-1). Ab initio calculations reproduce this number to
      within 10% if the monomer units and the molecular frame are allowed to fully
      relax as the internal rotation takes place. The binding energies of H(3)N-HF and
      H(3)N-HF-HF, calculated at the MP2/aug-cc-pVTZ level and corrected for basis set
      superposition error are 12.3 and 22.0 kcal/mol, respectively. Additional energy
      calculations have been performed to explore the lowest frequency vibration of
      H(3)N-HF-HF, a ring-opening motion that increases the NFF angle. The addition of
      one HF molecule to H(3)N-HF represents the first step of microsolvation of a
      hydrogen bonded complex and the results of this study demonstrate that a single,
      polar near-neighbor has a significant influence on the extent of proton transfer
      across the hydrogen bond. As measured using the proton-transfer parameter
      rho(PT), previously defined by Kurnig and Scheiner [Int. J. Quantum Chem.,
      Quantum Biol. Symp. 1987, 14, 47], the degree of proton transfer in H(3)N-HF-HF
      is greater than that in either (CH(3))(3)N-HF or H(3)N-HCl but less than that in
      (CH(3))(3)N-HCl.

PMID- 14599224
TI  - Deuterium isotope effects on hydrophobic interactions: the importance of
      dispersion interactions in the hydrophobic phase.
AB  - Hydrogen/deuterium isotope effects on hydrophobic binding were examined by means
      of reversed-phase chromatographic separation of protiated and deuterated
      isotopologue pairs for a set of 10 nonpolar and low-polarity compounds with 10
      stationary phases having alkyl and aryl groups bonded to the silica surface. It
      was found that protiated compounds bind to nonpolar moieties attached to silica
      more strongly than deuterated ones, demonstrating that the CH/CD bonds of the
      solutes are weakened or have less restricted motions when bound in the stationary
      phase compared with the aqueous solvent (mobile phase). The interactions
      responsible for binding have been further characterized by studies of the effects
      of changes in mobile phase composition, temperature dependence of binding, and
      QSRR (quantitative structure-chromatographic retention relationship) analysis,
      demonstrating the importance of enthalpic effects in binding and differentiation
      between the isotopologues. To explain our results showing the active role of the
      hydrophobic (stationary) phase we propose a plausible model that includes
      specific contributions from aromatic edge-to-face attractive interactions and
      attractive interactions of aliphatic groups with the pi clouds of aromatic groups
      present as the solute or in the stationary phase.

PMID- 14599226
TI  - The electronic structure of the photoexcited triplet state of free-base
      (tetraphenyl)porphyrin by time-resolved electron-nuclear double resonance and
      density functional theory.
AB  - The photoexcited triplet states of free-base porphyrin (H(2)P) and free-base
      tetraphenylporphyrin (H(2)TPP) have been investigated by time-resolved electron
      paramagnetic resonance and electron-nuclear double resonance in a toluene glass
      at 80 K. Both the zero-field splitting parameters, D and E, and the proton A(zz)
      hyperfine coupling tensor components could be determined. D is about 13% larger
      in H(2)P than in H(2)TPP. In contrast, however, the A(zz) hyperfine coupling
      tensor components showed differences of less than 2%. To aid the understanding of
      these results, the electronic structures of H(2)P and H(2)TPP have been modeled
      using density functional theory. The geometrical structures of both molecules in
      their lowest triplet states were calculated using the Becke3 Lee-Yang-Parr
      composite exchange correlation functional and the 6-31G* basis set. Hyperfine
      couplings for these structures were calculated using the same functional but with
      the extended EPR-II basis set. These allow unambiguous assignment of the
      experimentally determined couplings. The theoretical values for H(2)P and H(2)TPP
      agree with the experimental values in that the presence of the phenyl groups has
      only a small effect on the unpaired electron spin-density distribution. The
      difference in sensitivity of the zero-field splitting parameters and the
      hyperfine couplings to mesophenyl substitution is discussed in terms of the wave
      functions of the four frontier orbitals of porphyrins introduced by Gouterman.

PMID- 14599227
TI  - Ile, Leu, and Val methyl assignments of the 723-residue malate synthase G using a
      new labeling strategy and novel NMR methods.
AB  - New NMR experiments are presented for the assignment of methyl (13)C and (1)H
      chemical shifts from Ile, Leu, and Val residues in high molecular weight
      proteins. The first class of pulse schemes transfers magnetization from the
      methyl group to the backbone amide spins for detection, while the second more
      sensitive class uses an "out-and-back" transfer scheme in which side-chain
      carbons or backbone carbonyls are correlated with methyl (13)C and (1)H spins.
      Both groups of experiments benefit from a new isotopic labeling scheme for
      protonation of Leu and Val methyl groups in large deuterated proteins. The
      approach makes use of alpha-ketoisovalerate that is (13)C-labeled and protonated
      in one of its methyl groups ((13)CH(3)), while the other methyl is (12)CD(3). The
      use of this biosynthetic precursor leads to production of Leu and Val residues
      that are (13)CH(3)-labeled at only a single methyl position. Although this
      labeling pattern effectively reduces by 2-fold the concentration of Leu and Val
      methyls in NMR samples, it ensures linearity of Val and Leu side-chain (13)C spin
      systems, leading to higher sensitivity and, for certain classes of experiments,
      substantial simplification of NMR spectra. Very near complete assignments of the
      276 Ile (delta 1 only), Leu, and Val methyl groups in the single-chain 723
      residue enzyme malate synthase G (MSG, molecular tumbling time 37 +/- 2 ns at 37
      degrees C) have been obtained using the proposed isotopic labeling strategy in
      combination with the new NMR experiments.

PMID- 14599228
TI  - Insights into the structure and reactivity of acylperoxo complexes in the Kochi
      Jacobsen-Katsuki catalytic system. A density functional study.
AB  - Structural properties of the acylperoxo complexes [(Salen)Mn(III)RCO(3)] (2) and
      [(Salen)Mn(IV)RCO(3)] (3), the critical intermediates in the Kochi-Jacobsen
      Katsuki reaction utilizing organic peracids or O(2)/aldehydes as oxygen source,
      have been studied with the density functional theory. Four distinct isomers,
      cis(O,N), cis(N,O), cis(N,N), and trans, of these complexes have been located.
      The isomer 2-cis(O,N) in its quintet ground state, and nearly degenerate isomers
      3-cis(O,N) and 3-cis(N,O) in their quartet ground states are found to be the
      lowest in energy among the other isomers. The O-O bond cleavage in the cis(O,N),
      cis(N,O), and trans isomers of 2 and 3 has been elucidated. In complex 3, the O-O
      bond is inert. On the contrary, in complex 2, the O-O bond cleaves via two
      distinct pathways. The first pathway occurs exclusively on the quintet potential
      energy surface (PES) and corresponds to heterolytic O-O bond scission coupled
      with insertion of an oxygen atom into an Mn-N(Salen) bond to form 2-N-oxo
      species; this pathway has the lowest barrier of 14.9 kcal/mol and is 15.6
      kcal/mol exothermic. The second pathway is tentatively a spin crossover pathway.
      In particular, for 2-cis(O,N) and 2-cis(N,O) the second pathway proceeds through
      a crucial minimum on the seam of crossing (MSX) between the quintet and triplet
      PESs followed by heterolytic O-O cleavage on the triplet PES, and produces
      unusual triplet 2-cis(O,N)- and 2-cis(N,O)-oxo ([(Salen)Mn(V)(O)RCO(2)]) species;
      this pathway requires 12.8 kcal/mol and is 1.4 kcal/mol endothermic. In contrast,
      for the 2-trans isomer, spin crossing is less crucial and the O-O cleavage
      proceeds homolytically to generate 2-trans-oxo [(Salen)Mn(IV)(O)] species with
      RCO(2) radical; this pathway, however, cannot compete with that in 2-cis because
      it needs 21.9 kcal/mol for activation and is 15.3 kcal/mol endothermic. In
      summary, the O-O cleavage occurs predominantly in the 2-cis complexes, and may
      proceed either through pure high spin or spin crossover heterolytic pathway to
      produce 2-cis-oxo and 2-N-oxo species.

PMID- 14599229
TI  - Functional dynamics of ion channels: modulation of proton movement by
      conformational switches.
AB  - Detailed comparative studies of proton relay in native and chemically modified
      gramicidin channels provide a unique opportunity to uncover the structural basis
      of biological proton transport. The function of ion channels hinges on their
      ability to provide surrogate solvation in narrow pore filters so as to overcome
      the dielectric barrier presented by biological membranes. In the potassium
      channel KcsA and in the cation channel gramicidin, permeant selectivity and
      mobility are determined by the proteinaceous matrix via hydrogen bonding, charge
      dipole, and dipole-dipole interactions. In particular, main-chain carbonyl groups
      in these pore interiors play an essential role in the solvation of alkali ions
      and of protons. In this study, molecular dynamics simulations reveal how the
      translocation of H(+) is controlled by nanosecond conformational transitions
      exchanging distorted states of the peptidic backbone in the single-file region of
      a dioxolane-linked analogue of the gramicidin dimer. These results underline the
      functional role of channel dynamics and provide a mechanism for the modulation of
      proton currents by fluctuating dipoles.

PMID- 14599230
TI  - Selective binding of monovalent cations to the stacking G-quartet structure
      formed by guanosine 5'-monophosphate: a solid-state NMR study.
AB  - We report a solid-state multinuclear ((23)Na, (15)N, (13)C, and (31)P) NMR study
      on the relative affinity of monovalent cations for a stacking G-quartet structure
      formed by guanosine 5'-monophosphate (5'-GMP) self-association at pH 8. Two major
      types of cations are bound to the 5'-GMP structure: one at the surface and the
      other within the channel cavity between two G-quartets. The channel cation is
      coordinated to eight carbonyl oxygen atoms from the guanine bases, whereas the
      surface cation is close to the phosphate group and likely to be only partially
      hydrated. On the basis of solid-state (23)Na NMR results from a series of ion
      titration experiments, we have obtained quantitative thermodynamic parameters
      concerning the relative cation binding affinity for each of the two major binding
      sites. For the channel cavity site, the values of the free energy difference
      (Delta G degrees at 25 degrees C) for ion competition between M(+) and Na(+) ions
      are K(+) (-1.9 kcal mol(-1)), NH(4)(+) (-1.8 kcal mol(-1)), Rb(+) (-0.3 kcal mol(
      1)), and Cs(+) (1.8 kcal mol(-1)). For the surface site, the values Delta G
      degrees are K(+) (2.5 kcal mol(-1)), NH(4)(+) (-1.3 kcal mol(-1)), Rb(+) (1.1
      kcal mol(-1)), and Cs(+) (0.9 kcal mol(-1)). Solid-state NMR data suggest that
      the affinity of monovalent cations for the 5'-GMP structure follows the order
      NH(4)(+) > Na(+) > Cs(+) > Rb(+) > K(+) at the surface site and K(+) > NH(4)(+) >
      Rb(+) > Na(+) > Cs(+) > Li(+) at the channel cavity site. We have found that the
      cation-induced stability of a 5'-GMP structure is determined only by the affinity
      of monovalent cations for the channel site and that the binding of monovalent
      cations to phosphate groups plays no role in 5'-GMP self-ordered structure. We
      have demonstrated that solid-state (23)Na and (15)N NMR can be used
      simultaneously to provide mutually complementary information about competitive
      binding between Na(+) and NH(4)(+) ions.

PMID- 14599233
TI  - Systems modelling of the relationship between training and performance.
AB  - Mathematical models may provide a method of describing and predicting the effect
      of training on performance. The current models attempt to describe the effects of
      single or multiple bouts of exercise on the performance of a specific task on a
      given day. These models suggest that any training session increases fitness and
      provokes a fatigue response. Various methods of quantifying the training stimulus
      (training impulse, absolute work, psychophysiological rating) and physical
      performance (criterion scale, arbitrary units) are employed in these models. The
      models are empirical descriptions and do not use current knowledge regarding the
      specificity of training adaptations. Tests of these models with published data
      indicate discrepancies between the predicted and measured time course of
      physiological adaptations, and between the predicted and measured performance
      responses to training. The relationship between these models and the underlying
      physiology requires clarification. New functional models that incorporate
      specificity of training and known physiology are required to enhance our ability
      to guide athletic training, rehabilitation and research.

PMID- 14599232
TI  - Effect of exercise intensity, duration and mode on post-exercise oxygen
      consumption.
AB  - In the recovery period after exercise there is an increase in oxygen uptake
      termed the 'excess post-exercise oxygen consumption' (EPOC), consisting of a
      rapid and a prolonged component. While some studies have shown that EPOC may last
      for several hours after exercise, others have concluded that EPOC is transient
      and minimal. The conflicting results may be resolved if differences in exercise
      intensity and duration are considered, since this may affect the metabolic
      processes underlying EPOC. Accordingly, the absence of a sustained EPOC after
      exercise seems to be a consistent finding in studies with low exercise intensity
      and/or duration. The magnitude of EPOC after aerobic exercise clearly depends on
      both the duration and intensity of exercise. A curvilinear relationship between
      the magnitude of EPOC and the intensity of the exercise bout has been found,
      whereas the relationship between exercise duration and EPOC magnitude appears to
      be more linear, especially at higher intensities. Differences in exercise mode
      may potentially contribute to the discrepant findings of EPOC magnitude and
      duration. Studies with sufficient exercise challenges are needed to determine
      whether various aerobic exercise modes affect EPOC differently. The relationships
      between the intensity and duration of resistance exercise and the magnitude and
      duration of EPOC have not been determined, but a more prolonged and substantial
      EPOC has been found after hard- versus moderate-resistance exercise. Thus, the
      intensity of resistance exercise seems to be of importance for EPOC. Lastly,
      training status and sex may also potentially influence EPOC magnitude, but this
      may be problematic to determine. Still, it appears that trained individuals have
      a more rapid return of post-exercise metabolism to resting levels after
      exercising at either the same relative or absolute work rate; however, studies
      after more strenuous exercise bouts are needed. It is not determined if there is
      a sex effect on EPOC. Finally, while some of the mechanisms underlying the more
      rapid EPOC are well known (replenishment of oxygen stores, adenosine
      triphosphate/creatine phosphate resynthesis, lactate removal, and increased body
      temperature, circulation and ventilation), less is known about the mechanisms
      underlying the prolonged EPOC component. A sustained increased circulation,
      ventilation and body temperature may contribute, but the cost of this is low. An
      increased rate of triglyceride/fatty acid cycling and a shift from carbohydrate
      to fat as substrate source are of importance for the prolonged EPOC component
      after exhaustive aerobic exercise. Little is known about the mechanisms
      underlying EPOC after resistance exercise.

PMID- 14599231
TI  - Exercise and the nitric oxide vasodilator system.
AB  - In the past two decades, normal endothelial function has been identified as
      integral to vascular health. The endothelium produces numerous vasodilator and
      vasoconstrictor compounds that regulate vascular tone; the vasodilator, nitric
      oxide (NO), has additional antiatherogenic properties, is probably the most
      important and best characterised mediator, and its intrinsic vasodilator function
      is commonly used as a surrogate index of endothelial function. Many conditions,
      including atherosclerosis, diabetes mellitus and even vascular risk factors, are
      associated with endothelial dysfunction, which, in turn, correlates with
      cardiovascular mortality. Furthermore, clinical benefit and improved endothelial
      function tend to be associated in response to interventions. Shear stress on
      endothelial cells is a potent stimulus for NO production. Although the role of
      endothelium-derived NO in acute exercise has not been fully resolved, exercise
      training involving repetitive bouts of exercise over weeks or months up-regulates
      endothelial NO bioactivity. Animal studies have found improved endothelium
      dependent vasodilation after as few as 7 days of exercise. Consequent changes in
      vasodilator function appear to persist for several weeks but may regress with
      long-term training, perhaps reflecting progression to structural adaptation which
      may, however, have been partly endothelium-dependent. The increase in blood flow,
      and change in haemodynamics that occur during acute exercise may, therefore,
      provide a stimulus for both acute and chronic changes in vascular function.
      Substantial differences within species and within the vasculature appear to
      exist. In humans, exercise training improves endothelium-dependent vasodilator
      function, not only as a localised phenomenon in the active muscle group, but also
      as a systemic response when a relatively large mass of muscle is activated
      regularly during an exercise training programme. Individuals with initially
      impaired endothelial function at baseline appear to be more responsive to
      exercise training than healthy individuals; that is, it is more difficult to
      improve already normal vascular function. While improvement is reflected in
      increased NO bioactivity, the detail of mechanisms, for example the relative
      importance of up-regulation of mediators and antioxidant effects, is unclear.
      Optimum training schedules, possible sequential changes and the duration of
      benefit under various conditions also remain largely unresolved. In summary,
      epidemiological evidence strongly suggests that regular exercise confers
      beneficial effects on cardiovascular health. Shear stress-mediated improvement in
      endothelial function provides one plausible explanation for the cardioprotective
      benefits of exercise training.

PMID- 14599234
TI  - Meniscal and chondral loss in the anterior cruciate ligament injured knee.
AB  - Rupture of the anterior cruciate ligament (ACL) of the knee is a commonly
      occurring injury in the athletic population. Associated meniscal and chondral
      injury is well recognised. This occurs both at the time of index injury and also
      secondarily over time in the ACL-deficient knee as a result of several related
      pathways culminating in osteoarthritis. ACL reconstruction is a well established
      surgical technique for treatment of symptomatic instability in ACL-deficient
      knees but the role of ACL reconstruction in the prevention of osteoarthritis
      remains unclear. This article reviews the contemporary literature on the
      pathophysiology of chondral and meniscal loss in ACL-injured knees and the role
      of current treatment techniques, including surgical reconstruction of
      ligamentous, meniscal and chondral pathology, in altering the natural history of
      the ACL-deficient knee.

PMID- 14599235
TI  - Cryopreserved human hepatocytes as alternative in vitro model for cytochrome p450
      induction studies.
AB  - Induction of cytochrome P450 (CYP) by drugs is one of major concerns for drug
      drug interactions. Thus, the assessment of CYP induction by novel compounds is a
      vital component in the drug discovery and development processes. Primary human
      hepatocytes are the preferred in vitro model for predicting CYP induction in
      vivo. However, their use is hampered by the erratic supply of human tissue and
      donor-to-donor variability. Although cryopreserved hepatocytes have been
      recommended for short-term applications in suspension, their use in studies on
      induction of enzyme activity has been limited because of poor attachment and
      response to enzyme inducers. In this study, we report culture conditions that
      allowed the attachment of cryopreserved human hepatocytes and responsiveness to
      CYP inducers. We evaluated the inducibility of CYP1A1/2 and CYP3A4 enzymes in
      cryopreserved hepatocytes from three human donors. Cryopreserved human
      hepatocytes were cultured in serum-free medium for 4 d. They exhibited normal
      morphology and measurable viability as evaluated by the reduction of tetrazolium
      salts (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)
      2H-tetrazolium, inner salt) by cellular dehydrogenases. Treatment with beta
      naphthoflavone (10 microM) for 3 d increased ethoxyresorufin-O-deethylase
      activity (CYP1A1/2) by 6- to 11-fold over untreated cultures and increased CYP1A2
      messenger ribonucleic acid (mRNA) expression by three- to eightfold. Similarly,
      treatment of cryopreserved human hepatocytes with rifampicin (25 microM) for 3 d
      increased testosterone 6 beta-hydroxylase activity (CYP3A4) by five- to eightfold
      over untreated cultures and increased CYP3A4 mRNA expression by four- to
      eightfold. The results suggest that cryopreserved human hepatocytes can be a
      suitable in vitro model for evaluating xenobiotics as inducers of CYP1A1/2 and
      CYP3A4 enzymes.

PMID- 14599236
TI  - Modeling hippocampal and neocortical contributions to recognition memory: a
      complementary-learning-systems approach.
AB  - The authors present a computational neural-network model of how the hippocampus
      and medial temporal lobe cortex (MTLC) contribute to recognition memory. The
      hippocampal component contributes by recalling studied details. The MTLC
      component cannot support recall, but one can extract a scalar familiarity signal
      from MTLC that tracks how well a test item matches studied items. The authors
      present simulations that establish key differences in the operating
      characteristics of the hippocampal-recall and MTLC-familiarity signals and
      identify several manipulations (e.g., target-lure similarity, interference) that
      differentially affect the 2 signals. They also use the model to address the
      stochastic relationship between recall and familiarity and the effects of partial
      versus complete hippocampal lesions on recognition.

PMID- 14599237
TI  - Modeling language acquisition in atypical phenotypes.
AB  - An increasing number of connectionist models have been proposed to explain
      behavioral deficits in developmental disorders. These simulations motivate
      serious consideration of the theoretical implications of the claim that a
      developmental disorder fits within the parameter space of a particular
      computational model of normal development. The authors examine these issues in
      depth with respect to a series of new simulations investigating past-tense
      formation in Williams syndrome. This syndrome and the past-tense domain are
      highly relevant because both have been used to make strong theoretical claims
      about the processes underlying normal language acquisition. The authors conclude
      that computational models have great potential to advance psychologists'
      understanding of developmental deficits because they focus on the developmental
      process itself as a pivotal causal factor in producing atypical phenotypic
      outcomes.

PMID- 14599238
TI  - Incremental planning in sequence production.
AB  - People produce long sequences such as speech and music with incremental planning:
      mental preparation of a subset of sequence events. The authors model in music
      performance the sequence events that can be retrieved and prepared during
      production. Events are encoded in terms of their serial order and timing relative
      to other events in a planning increment, a contextually determined distribution
      of event activations. Planning is facilitated by events' metrical similarity and
      serial/temporal proximity and by developmental changes in short-term memory. The
      model's predictions of larger planning increments as production rate decreases
      and as producers' age-experience increases are confirmed in serial-ordering
      errors produced by adults and children. Incremental planning is considered as a
      general retrieval constraint in serially ordered behaviors.

PMID- 14599239
TI  - Four routes of cognitive evolution.
AB  - Four routes of cognitive evolution are distinguished: phylogenetic construction,
      in which natural selection produces qualitative change to the way a cognitive
      mechanism operates (language); phylogenetic inflection, in which natural
      selection biases the input to a cognitive mechanism (imprinting and spatial
      memory); ontogenetic construction, in which developmental selection alters the
      way a cognitive mechanism operates (face recognition and theory of mind); and
      ontogenetic inflection, in which developmental selection changes the input to a
      cognitive mechanism (imitation). This framework integrates findings from
      evolutionary psychology (i.e., all research on the evolution of mentality and
      behavior). In contrast with human nativist evolutionary psychology, it recognizes
      the adaptive significance of developmental processes, conserves the distinction
      between cognitive and noncognitive mechanisms, and encompasses research on human
      and nonhuman animals.

PMID- 14599240
TI  - Neuropsychological dissociations between priming and recognition: a single-system
      connectionist account.
AB  - A key claim of current theoretical analyses of the memory impairments associated
      with amnesia is that certain distinct forms of learning and memory are spared. A
      compelling example is that amnesic patients and controls are indistinguishable in
      repetition priming but amnesic patients are impaired at recognizing the study
      items. The authors show that this pattern of results is predicted by a single
      system connectionist model of learning in which amnesia is simulated by a reduced
      learning rate. They also demonstrate that the model can reproduce the converse
      pattern in which priming but not recognition is impaired if the input is assumed
      to be additionally degraded in a priming test. The authors conclude that
      dissociations between priming and recognition do not require functionally or
      neurally distinct memory systems.

PMID- 14599241
TI  - Adapted to flee famine: adding an evolutionary perspective on anorexia nervosa.
AB  - Anorexia nervosa (AN) is commonly attributed to psychological conflicts, attempts
      to be fashionably slender, neuroendocrine dysfunction, or some combination of
      these factors. Considerable research reveals these theories to be incomplete.
      Psychological and societal factors account for the decision to diet but not for
      the phenomenology of the disorder; theories of biological defects fail to explain
      neuroendocrine findings that suggest coordinated physiological mechanisms. This
      article presents evidence that AN's distinctive symptoms of restricting food,
      denial of starvation, and hyperactivity are likely to be evolved adaptive
      mechanisms that facilitated ancestral nomadic foragers leaving depleted
      environments; genetically susceptible individuals who lose too much weight may
      trigger these archaic adaptations. This hypothesis accounts for the occurrence of
      AN-like syndromes in both humans and animals and is consistent with changes
      observed in the physiology, cognitions, and behavior of patients with AN.

PMID- 14599242
TI  - Recollection rejection: false-memory editing in children and adults.
AB  - Mechanisms for editing false events out of memory reports have fundamental
      implications for theories of false memory and for best practice in applied
      domains in which false reports must be minimized (e.g., forensic psychological
      interviews, sworn testimony). A mechanism posited in fuzzy-trace theory,
      recollection rejection, is considered. A process analysis of false-memory editing
      is presented, which assumes that false-but-gist-consistent events (e.g., the word
      SOFA, when the word COUCH was experienced) sometimes cue the retrieval of
      verbatim traces of the corresponding true events (COUCH), generating mismatches
      that counteract the high familiarity of false-but-gist-consistent events.
      Empirical support comes from 2 qualitative phenomena: recollective suppression of
      semantic false memory and inverted-U relations between retrieval time and
      semantic false memory. Further support comes from 2 quantitative methodologies:
      conjoint recognition and receiver operating characteristics. The analysis also
      predicts a novel false-memory phenomenon (erroneous recollection rejection), in
      which true events are inappropriately edited out of memory reports.

PMID- 14599243
TI  - The role of occlusion in the perception of depth, lightness, and opacity.
AB  - A theory is presented that explains how the visual system infers the lightness,
      opacity, and depth of surfaces from stereoscopic images. It is shown that the
      polarity and magnitude of image contrast play distinct roles in surface
      perception, which can be captured by 2 principles of perceptual inference. First,
      a contrast depth asymmetry principle articulates how the visual system computes
      the ordinal depth and lightness relationships from the polarity of local,
      binocularly matched image contrast. Second, a global transmittance anchoring
      principle expresses how variations in contrast magnitudes are used to infer the
      presence of transparent surfaces. It is argued that these principles provide a
      unified explanation of how the visual system computes the 3-D surface structure
      of opaque and transparent surfaces.

PMID- 14599244
TI  - I sell seashells by the seashore and my name is Jack: comment on Pelham,
      Mirenberg, and Jones (2002).
AB  - According to a new hypothesis based on implicit egotism, people gravitate toward
      cities, states, and careers with names similar to their own names. To support
      this hypothesis, B. W. Pelham, M. C. Mirenberg, and J. T. Jones (2002) reported a
      series of results regarding distributions of names in different cities, states,
      and jobs. In the present article, new analyses of the original data are reported,
      showing that the hypothesis is not supported for the large majority of names
      considered by the authors, and for some names even the opposite result is found.
      In addition, a meta-analysis reveals that either the data are unreliable, or the
      hypothesis cannot be supported in the whole population of names. Overall, the
      original data give no support of the idea that implicit egotism influences major
      life decisions.

PMID- 14599245
TI  - Assessing the validity of implicit egotism: a reply to Gallucci (2003).
AB  - B. W. Pelham, M. C. Mirenberg, and J. T. Jones (2002) argued that most people
      prefer stimuli that are associated with the self, a preference they called
      implicit egotism. In support of implicit egotism, Pelham et al presented evidence
      from 10 archival studies showing that people gravitate toward careers and places
      of residence that resemble their names or birthday numbers. M. Gallucci (2003)
      argued that alternate analyses of the same data provide strong evidence against
      implicit egotism. Whereas Gallucci was correct that Pelham et al's original
      analyses were flawed, their results remain significant even when more
      conservative tests are used. The authors also present new data in support of
      implicit egotism, including exhaustive studies of (a) common surnames and US city
      names and (b) common surnames and street names. The new studies also revealed
      that as sample sizes grow larger, studies are more likely to produce evidence of
      implicit egotism.

PMID- 14599246
TI  - Party over policy: The dominating impact of group influence on political beliefs.
AB  - Four studies demonstrated both the power of group influence in persuasion and
      people's blindness to it. Even under conditions of effortful processing,
      attitudes toward a social policy depended almost exclusively upon the stated
      position of one's political party. This effect overwhelmed the impact of both the
      policy's objective content and participants' ideological beliefs (Studies 1-3),
      and it was driven by a shift in the assumed factual qualities of the policy and
      in its perceived moral connotations (Study 4). Nevertheless, participants denied
      having been influenced by their political group, although they believed that
      other individuals, especially their ideological adversaries, would be so
      influenced. The underappreciated role of social identity in persuasion is
      discussed.

PMID- 14599247
TI  - Complementary justice: effects of "poor but happy" and "poor but honest"
      stereotype exemplars on system justification and implicit activation of the
      justice motive.
AB  - It was hypothesized that exposure to complementary representations of the poor as
      happier and more honest than the rich would lead to increased support for the
      status quo. In Study 1, exposure to "poor but happy" and "rich but miserable"
      stereotype exemplars led people to score higher on a general measure of system
      justification, compared with people who were exposed to noncomplementary
      exemplars. Study 2 replicated this effect with "poor but honest" and "rich but
      dishonest" complementary stereotypes. In Studies 3 and 4, exposure to
      noncomplementary stereotype exemplars implicitly activated justice concerns, as
      indicated by faster reaction times to justice-related than neutral words in a
      lexical decision task. Evidence also suggested that the Protestant work ethic may
      moderate the effects of stereotype exposure on explicit system justification (but
      not implicit activation).

PMID- 14599248
TI  - Defensive zeal and the uncertain self: what makes you so sure?
AB  - In Studies 1-3, undergraduates with high self-esteem (HSEs) reacted to personal
      uncertainty-threats with compensatory conviction about unrelated issues and
      aspects of the self. In Study 1 HSEs reacted to salience of personal dilemmas
      with increased implicit conviction about self-definition. In Study 2 they reacted
      to the same uncertainty-threat with increased explicit conviction about social
      issues. In Study 3, HSEs (particularly defensive HSEs, i.e., with low implicit
      self-esteem; C. H. Jordan, S. J. Spencer, & M. P. Zanna, 2003) reacted to
      uncertainty about a personal relationship with compensatory conviction about
      social issues. For HSEs in Study 4, expressing convictions about social issues
      decreased subjective salience of dilemma-related uncertainties that were not
      related to the social issues. Compensatory conviction is viewed as a mode of
      repression, akin to reaction formation, that helps keep unwanted thoughts out of
      awareness.

PMID- 14599249
TI  - Sexual harassment under social identity threat: the computer harassment paradigm.
AB  - Two laboratory experiments investigated the hypothesis that threat to male
      identity would increase the likelihood of gender harassment. In both experiments,
      using the computer harassment paradigm, male university students (N=80 in
      Experiment 1, N=90 in Experiment 2) were exposed to different types of identity
      threat (legitimacy threat and threat to group value in Experiment 1 and
      distinctiveness threat and prototypicality threat in Experiment 2) or to no
      threat and were then given the opportunity to send pornographic material to a
      virtual female interaction partner. Results show that (a) participants harassed
      the female interaction partner more when they were exposed to a legitimacy,
      distinctiveness, or prototypicality threat than to no threat; (b) this was mainly
      true for highly identified males; and (c) harassment enhanced postexperimental
      gender identification. Results are interpreted as supporting a social identity
      account of gender harassment.

PMID- 14599250
TI  - Carryover effects of feeling socially transparent or impenetrable on strategic
      self-presentation.
AB  - The authors proposed that social orientations, such as feeling transparent or
      impenetrable, that are created in one context can carry over and interact with
      elements in a different context to influence strategic self-presentation.
      Participants in 2 experiments wrote narratives that made them feel transparent or
      impenetrable. Later, they believed they would discuss problems from a social
      intelligence test with other group members and believed they could do well or
      poorly on the problems on the basis of practice test feedback. Self-presentations
      of social intelligence revealed the hypothesized interactions. When transparent,
      participants adjusted their self-presentations to how well or poorly they
      expected to perform, but when impenetrable, they presented themselves positively
      regardless of performance expectations. These results mimic effects obtained when
      performance is actually made publicly accessible or inaccessible, broaden the
      conceptualization of strategic self-presentation, and call into question long
      held assumptions surrounding public versus private manipulations.

PMID- 14599251
TI  - When accuracy hurts, and when it helps: a test of the empathic accuracy model in
      marital interactions.
AB  - This study tested predictions from W. Ickes and J. A. Simpson's (1997, 2001)
      empathic accuracy model. Married couples were videotaped as they tried to resolve
      a problem in their marriage. Both spouses then viewed a videotape of the
      interaction, recorded the thoughts and feelings they had at specific time points,
      and tried to infer their partner's thoughts and feelings. Consistent with the
      model, when the partner's thoughts and feelings were relationship-threatening (as
      rated by both the partners and by trained observers), greater empathic accuracy
      on the part of the perceiver was associated with pre-to-posttest declines in the
      perceiver's feelings of subjective closeness. The reverse was true when the
      partner's thoughts and feelings were nonthreatening. Exploratory analyses
      revealed that these effects were partially mediated through observer ratings of
      the degree to which partners tried to avoid the discussion issue.

PMID- 14599252
TI  - Contingencies of self-worth in college students: theory and measurement.
AB  - The Contingencies of Self-Worth Scale assesses 7 sources of self-esteem in
      college students: academics, appearance, approval from others, competition,
      family support, God's love, and virtue. In confirmatory factor analyses on data
      from 1,418 college students, a 7-factor model fit to the data acceptably well and
      significantly better than several plausible alternative models. The subscales all
      have high internal consistency, test-retest reliability, are distinct from other
      personality measures, and have a simplex structure arrayed on a continuum from
      external to internal sources of self-esteem. Contingencies of self-worth assessed
      prior to college predicted how students spent their time during their 1st year of
      college.

PMID- 14599253
TI  - A multidimensional structure for repetitive thought: what's on your mind, and
      how, and how much?
AB  - Although repetitive thought (RT) styles such as worry, rumination, and processing
      correlate positively, they have divergent effects on well-being, suggesting
      important dimensional variation. In Study 1, multidimensional scaling identified
      2 dimensions--positive versus negative content valence and searching versus
      solving purpose--among students (N=978) who completed standard RT measures. In
      Study 2, students (N=100) sorted 25 descriptions of RT. Multidimensional scaling
      identified 4 dimensions, including valence and purpose. Content valence
      associated with valenced affect; solving associated with less aroused affect and
      less polarized appraisals of thought topics. In Study 3, valence and purpose of
      RT descriptions by women in a breast cancer prevention trial (N=62) predicted
      concurrent affect and psychological and physical well-being.

PMID- 14599254
TI  - Exploring the influence of personality on depressive symptoms and self-esteem
      across a significant life transition.
AB  - This study investigates the influence of personality on adjustment to a
      particular life transition, community relocation. Participants were 285 women
      (average age=69.5) who were interviewed once before they moved, and then multiple
      times after the move. Within the context of this multiwave design, personality
      traits were used to predict changes in depressive symptoms (DS) and self-esteem
      (SE) across the move. Neuroticism and Openness to Experience predicted increases
      in DS over time, whereas Extraversion and Openness predicted increases in SE.
      Stressful reactions to the move and sense of mastery about the move partially
      mediated these effects. The study documents the dynamic influence of personality
      on positive and negative aspects of adjustment and investigates differing routes
      through which such effects occur.

PMID- 14599255
TI  - The relational-interdependent self-construal, self-concept consistency, and well
      being.
AB  - Examination of the assumptions underlying consistency perspectives in social and
      personality psychology reveals that they are based on an independent,
      individualistic view of the self. If the self is constructed as relational or
      interdependent with others, consistency may be less important in social behavior
      and well-being. Using a variety of measures of well-being, the studies showed
      that there is a weaker relation between consistency and well-being for
      individuals with a highly relational self-construal than for those with a low
      relational self-construal. Study 3 examined the association between the self
      construal, consistency, authenticity, and well-being. These findings reveal the
      importance of a cultural analysis of theories of the self, personality, and well
      being for further theory development.

PMID- 14599256
TI  - Reconstructive memory related to adolescent-parent conflict interactions: the
      influence of attachment-related representations on immediate perceptions and
      changes in perceptions over time.
AB  - This investigation examined the hypothesis that individuals change, over time,
      their perceptions of interactions with attachment figures in ways that are
      consistent with their attachment-related representations of those individuals. In
      an original and a replication study, adolescents participated in laboratory
      conflict discussions with each of their parents. Adolescents rated their
      perceptions of the interactions immediately after the conflict discussions, then
      again 6 weeks later. Results indicated that (a) adolescents' immediate
      perceptions of the interactions were influenced by their attachment-related
      representations of their parents, and (b) adolescents' perceptions, over a period
      of 6 weeks, shifted such that their later perceptions were more congruent with
      their attachment-related representations than were their immediate perceptions.
      Implications for the continuity of relational models and relationship patterns
      are discussed.

PMID- 14599257
TI  - How do respondents construe ambiguous response formats of affect items?
AB  - Ambiguous response formats predict correlations from -.467 to -1 between opposite
      items, depending on whether the respondent's interpretation of the format is
      unipolar or bipolar. The authors present a procedure to investigate the proper
      interpretation in each case. It consists of applying nonparametric and parametric
      item response theory models (the Mokken and the graded response models) to pairs
      of opposite items in order to find the locations of the response options along
      the latent scale and, therefore, identify the response format construction. The
      authors tested this procedure on 4 samples (Ns=142-1,150) and 2 item pairs
      ("relaxed"-"tense" and "optimistic"-"pessimistic"). The results revealed that
      respondents constructed the formats as bipolar and supported the bipolarity of
      the item pairs.

PMID- 14599258
TI  - Secure and defensive high self-esteem.
AB  - Long-standing theories have suggested high self-esteem (SE) can assume
      qualitatively different forms that are related to defensiveness. The authors
      explored whether some high-SE individuals are particularly defensive because they
      harbor negative self-feelings at less conscious levels, indicated by low implicit
      SE. In Study 1, participants high in explicit SE but low in implicit SE showed
      the highest levels of narcissism--an indicator of defensiveness. In Studies 2 and
      3, the correspondence between implicit and explicit SE predicted defensive
      behavior (in-group bias in Study 2 and dissonance reduction in Study 3), such
      that for high explicit-SE participants, those with relatively low implicit SE
      behaved more defensively. These results are consistent with the idea that high SE
      can be relatively secure or defensive.

PMID- 14599259
TI  - Zolpidem-related effects on performance and mood during simulated night-shift
      work.
AB  - The effects of zolpidem, a nonbenzodiazepine hypnotic, on psychomotor task
      performance, subjective effects, and food intake were examined during simulated
      shift work. Seven participants completed this 23-day, within-participant design,
      residential laboratory study. They received a single oral zolpidem dose (0, 5, or
      10 mg) 1 hr before bedtime for 3 consecutive days under 2 shift conditions: day
      shift and night shift. When participants received placebo, next-day performance
      and subjective effects were disrupted, and food intake was decreased during the
      night shift. Zolpidem improved subjective reports of sleep quality and, to a
      lesser extent, next-day performance. Next-day mood, however, was worsened by
      zolpidem. Food intake was unaffected by zolpidem. These data indicate that shift
      changes produce performance impairments, mood alterations, and decreases in food
      intake, and that zolpidem attenuates some shift-change-related disruptions.

PMID- 14599260
TI  - The subjective and reinforcing effects of visual and olfactory stimuli in alcohol
      drinking.
AB  - Nonpharmacological cues associated with drug intake may influence subjective and
      reinforcing effects of those drugs. Social drinkers (N = 80) participated in 2
      sessions in which they rated and then consumed ad lib their preferred beer (with
      participants blind to brand). Visual and olfactory stimuli were obscured during 1
      session (blocked) and not obscured during the other (unblocked). Dependent
      measures included ratings of "liking", "want another", and "desire to drink";
      subjective mood; and ad lib beer consumption (reinforcement). Most ratings and ad
      lib consumption were lower during the blocked versus the unblocked condition.
      There were no interactions of blockade condition with sex and no effect of
      blockade on mood. These findings show that nonpharmacological stimuli associated
      with alcohol consumption influence alcohol's subjective and reinforcing effects.

PMID- 14599261
TI  - Smoking withdrawal dynamics: III. Correlates of withdrawal heterogeneity.
AB  - Five parameters of postcessation smoking withdrawal variability derived from
      clinical data (T. M. Piasecki, D. E. Jorenby, S. S. Smith, M. C. Fiore, & T. B.
      Baker, 2003a, 2003b) were predicted from baseline measures and pharmacotherapy
      assignment. Smokers who were more dependent, older, and high in negative affect
      reported more severe withdrawal. Women, heavier smokers, and those with a history
      of depression reported more variable symptoms. Smokers treated with nicotine
      patch, bupropion, or both reported less severe withdrawal than did those given
      placebo, but medication did not affect the slope of symptoms over time, day-to
      day variability of symptoms, or the size of acute changes in symptoms associated
      with lapses to smoking. Prior research has shown that these symptom facets
      predict later relapse: thus, current pharmacotherapies may aid cessation by
      diminishing withdrawal severity, but they do not affect all clinically important
      aspects of withdrawal.

PMID- 14599263
TI  - The accessibility of motivational tendencies toward alcohol: approach, avoidance,
      and disinhibited drinking.
AB  - Problematic drinking has been proposed to result from an overactivation of
      approach motivation toward the beneficial effects of alcohol and an
      underactivation of avoidance motivation away from aversive consequences of heavy
      alcohol use. The authors of the present study used a sequential priming task (R.
      H. Fazio, J. R. Jackson, B. C. Dunton, & C. J. Williams, 1995) to examine the
      extent to which alcohol cues automatically activate approach and avoidance
      motivational tendencies in college drinkers. Hierarchical regression analyses
      indicate that number of binge episodes and alcohol problems are correlated with
      weak associations between alcohol cues and avoidance motivation but not with
      strong associations between alcohol cues and approach motivation. Implications
      for understanding the self-regulation of alcohol use in college drinkers are
      discussed.

PMID- 14599262
TI  - Discriminative stimulus effects of the cannabinoid antagonist, SR 141716A, in
      delta -sup-9-tetrahydrocannabinol-treated rhesus monkeys.
AB  - This study examined whether the cannabinoid antagonist, SR 141716A, could be
      established as a discriminative stimulus in rhesus monkeys treated with delta 
      sup-9-tetrahydrocannabinol (delta -sup-9-THC). Stimulus control was established
      with SR 141716A (1.0 mg/kg) in 3 delta -sup-9-THC-treated monkeys (1.12
      mg/kg/day) in 113-124 sessions. The SR 141716A discriminative stimulus was dose
      related, attenuated by an acute injection of delta -sup-9-THC, and not mimicked
      by cocaine or ketamine. SR 141716A-appropriate responding occasioned by temporary
      discontinuation of delta -sup-9-THC treatment was attenuated by delta -sup-9-THC
      and not ketamine. The SR 141716A discriminative stimulus in delta -sup-9-THC
      treated monkeys appears to be mediated by cannabinoid receptors and could be
      related to delta -sup-9-THC withdrawal.

PMID- 14599264
TI  - Single- versus dual-drug target: effects in a brief abstinence incentive
      procedure.
AB  - The number of drugs targeted may have an important influence on the ability of
      drug abusers to abstain during motivational incentive procedures. The authors
      investigated outcomes in methadone maintenance patients (n = 58), who had
      evidence of both opiate and cocaine use, when continuous abstinence from cocaine
      only (single target) or from both cocaine and heroin (dual target) was required
      to earn US dollars 200 in voucher incentives over a 4-day period. Study patients
      were equally likely to initiate and sustain abstinence from cocaine under the
      single- versus the dual-drug target. They were more likely to initiate opiate
      abstinence under the dual-target condition, demonstrating sensitivity to
      reinforcer effects. Results suggest that adding a second drug target does not
      impede short-term cocaine abstinence initiation.

PMID- 14599265
TI  - MDMA and performance under a progressive-ratio schedule of water delivery.
AB  - This study investigated the possible motivational effects of (+-)3,4
      methylenedioxymethamphetamine (MDMA, ecstasy) in water-deprived rats responding
      under a progressive-ratio 2 schedule of water delivery. Lower doses (1.0 and 1.8
      mg/kg i.p.) had inconsistent effects on breakpoints and response rates, whereas
      higher doses (3.2 and 5.6 mg/kg ip) significantly decreased both response
      measures relative to vehicle control levels. Increasing the level of water
      restriction significantly increased both response measures, and decreasing
      restriction significantly decreased both response measures. This study found no
      evidence that MDMA increased the reinforcing efficacy of water, although prior
      findings have suggested that the drug might have such an effect. MDMA-induced
      changes in motor activity may account for the present results.

PMID- 14599266
TI  - An historical note on Darwin and nonhuman drug self-administration.
AB  - This note brings to the attention of readers a quote from Charles Darwin on the
      scientific implications of nonhuman drug self-administration. The quote is from
      The Descent of Man; and Selection in Relation to Sex (2nd ed.; C. Darwin,
      1874/1998). Consistent with Darwin's prescience in many areas of science, he
      discerned potential scientific importance in voluntary nonhuman drug self
      administration almost a century before that potential was realized in any
      substantive or systematic manner.

PMID- 14599267
TI  - Long-term memory deficits in schizophrenia: primary or secondary dysfunction?
AB  - Long-term memory impairment is often found in schizophrenia. The question remains
      whether this is caused by other cognitive deficits. One hundred eighteen first
      episode patients were compared with 45 control participants on several memory
      tasks. The role of processing speed and central executive functions on memory
      performance was examined with regression analysis for all participants and for
      patients separately. Deficits were found in general verbal learning performance
      and retrieval in episodic memory and semantic memory. Processing speed reduced
      disease-related variance in all memory variables. Coordination, organization of
      information, and speed of processing were the best predictors for long-term
      memory deficits in patients. The amount of explained variance, however, is small,
      especially in general verbal learning performance.

PMID- 14599269
TI  - Differential effects of left versus right mesial temporal lobe epilepsy on
      Wechsler intelligence factors.
AB  - This study investigates the effects of left versus right mesial temporal lobe
      epilepsy (MTLE) on Wechsler intelligence factors. In the left MTLE group, the
      Verbal Comprehension (VC) factor score was significantly lower than the
      Perceptual Organization (PO) factor score, whereas in the right MTLE group, the
      PO factor score was significantly lower than the VC factor score. The VC factor
      score was significantly lower for the left than the right MTLE group, whereas the
      PO factor score was significantly lower for the right than the left MTLE group.
      Thus, left versus right MTLE was associated with relative deficits in verbal
      versus nonverbal intelligence, respectively. These findings indicate that
      lateralized cognitive deficits in unilateral MTLE patients are not limited to the
      learning-memory domain but include more global intelligence functions.

PMID- 14599268
TI  - Predicting intellectual outcome among children treated with 35-40 Gy craniospinal
      irradiation for medulloblastoma.
AB  - Fifty children diagnosed with medulloblastoma completed 188 psychological
      evaluations using the Wechsler Intelligence Scales for Children (D. Wechsler,
      1974, 1991) over a 7-year study period following 35-40 Gy postoperative
      craniospinal irradiation. Random coefficient models were used to predict the
      trend in the children's intellectual performance as a function of time since
      diagnosis, with both patient and treatment variables as parameters of this
      function. A quadratic model demonstrated a delay prior to decline in performance
      for older patients, whereas the younger patients showed an immediate loss of
      performance with a plateau at approximately 6 years postdiagnosis. A steeper
      decline was found for those with higher baseline performance. Clinicians may use
      the proposed predictive model to identify those patients who are at risk of
      significant intellectual decline.

PMID- 14599270
TI  - Perceptual interactions between bilaterally presented words: what you get is
      often not what you see.
AB  - Bilateral presentations of words, 1 in the left visual hemifield (LVF) and 1 in
      the right (RVF), are used widely in studies of hemispheric asymmetry. However,
      although words shown centrally (i.e., nonlaterally) produce perceptual
      interactions in which 1 word alters the perceived identity of the other,
      perceptual interactions between bilaterally presented words have never been
      reported. To investigate this issue, the authors used brief, bilateral displays
      of words (e.g., romp-ramp) presented simultaneously. An eye tracker and forced
      choice task ensured appropriate presentation and testing. Report accuracy was
      greatest for RVF words. However, this was accompanied by perceptual interactions
      that occurred almost exclusively in responses to LVF words, indicating that RVF
      words often altered the perceived identity of LVF words but not vice versa.

PMID- 14599271
TI  - Interhemispheric interaction in bilateral redundancy gain: effects of stimulus
      format.
AB  - Previous visual laterality experiments have shown that identification is better
      when 2 copies of the same stimulus are presented--1 to each hemisphere--than when
      only a single copy is presented to 1 hemisphere. New experiments were conducted
      to vary whether the 2 stimuli on a bilaterally redundant trial were physically
      identical or identical in format in addition to leading to identical responses.
      Substantial bihemispheric gain was obtained even when the 2 stimuli were
      perceptually distinctive (e.g., letter trigrams differing in case and font or the
      same numeric quantity represented by digits and dots). Thus, much of the
      bihemispheric advantage involves relatively abstract aspects of information
      processing. However, when the formats were sufficiently distinctive, there were
      small effects on bihemispheric performance, suggesting some role for less
      abstract processes that are sensitive to physical characteristics.

PMID- 14599272
TI  - The hyperpriming phenomenon in normal aging: a consequence of cognitive slowing?
AB  - Increased semantic priming effects (hyperpriming) are sometimes observed in
      Alzheimer's disease (AD) and in normal aging. Whereas the processes underlying
      this phenomenon are now well understood in AD, the interpretation is much more
      woolly in normal aging. To explore semantic priming, the authors used a lexical
      decision task in which the influence of attention and cognitive slowing was
      controlled. To explore the semantic organization, the words had coordinate (tiger
      lion) or attribute relations (zebra-stripes). Priming scores of 21 older and 20
      young participants were equivalent in the 2 conditions. These results reflect the
      integrity of semantic memory with normal aging and call into question some
      investigations showing hyperpriming for older participants; this may instead be
      an artifact of a general slowing effect.

PMID- 14599273
TI  - Line bisection in the split brain.
AB  - The authors examined line bisection in 4 patients with resection of the corpus
      callosum and in 22 control participants. The control participants showed a
      leftward bias, especially with the left hand, implying right-hemispheric
      dominance in spatial attention. Two patients with anterior callosotomy showed
      similar biases, suggesting that the anterior callosum plays only a small role. A
      patient with complete callosotomy showed a strong right bias, regardless of hand
      use. A patient with posterior callosotomy showed the opposite pattern: a strong
      left bias, regardless of hand use. These data suggest that the posterior corpus
      callosum normally plays a role in line bisection and that the resection of the
      posterior corpus callosum produces consistent bias. The direction of the bias
      depends on which hemisphere assumes control.

PMID- 14599274
TI  - Abnormal activation of temporoparietal language areas during phonetic analysis in
      children with dyslexia.
AB  - Event-related magnetic fields were recorded using magnetoencephalography in
      children with (n=12) and without (n=11) dyslexia while they discriminated between
      pairs of syllables from a voice onset time series (/ga/-/ka/). Nonimpaired
      readers exhibited left-hemisphere predominance of activity after the resolution
      of the N1m, whereas children with dyslexia experienced a sharp peak of relative
      activation in right temporoparietal areas between 300 and 700 ms post-stimulus
      onset. Increased relative activation in right temporoparietal areas was
      correlated with reduced performance on phonological processing measures. Results
      are consistent with the notion that deficits in appreciating the sound structure
      of both written and spoken language are associated with abnormal
      neurophysiological activity in temporoparietal language areas in children with
      dyslexia.

PMID- 14599275
TI  - Delayed-onset deficits in verbal encoding strategies among patients with mild
      traumatic brain injury.
AB  - Knowledge obtained from longitudinal animal models was used to predict the course
      of verbal memory deficits in 19 concussed patients and 19 control patients who
      were given versions of the Hopkins Verbal Learning Test--Revised at 2 hr, 48 hr,
      and 1 week postconcussion. The physiological literature suggests that concussed
      patients should exhibit a decline in performance from 2 hr to 48 hr
      postconcussion on a measure of complex memory strategies. Consistent with this
      hypothesis, mixed-factor analysis of covariance revealed that concussed patients
      used less semantic clustering strategies than control patients at 48 hr
      postconcussion, whereas minimal differences were found at 2 hr postinjury.
      Furthermore, a chi-square analysis showed that a significant number of concussed
      patients experienced a decline in the number of semantic clusters they used from
      2 hr to 48 hr. No differences were found between the groups at the 1-week testing
      session.

PMID- 14599276
TI  - Questioning the living/nonliving dichotomy: evidence from a patient with an
      unusual semantic dissociation.
AB  - In this article the authors describe a patient (J.P.) whose category-specific
      naming deficit eluded the classical dichotomies between living versus nonliving
      items or visual versus functional attributes. At age 22, he had herpes simplex
      encephalitis followed by a left temporal lobectomy. J.P. was tested on measures
      of visual perception, category naming, fluency, and name-picture matching. He
      showed a severe impairment naming and identifying fruits, vegetables, and musical
      instruments. His performance with animals and birds was spared inconsistently,
      meaning that even the preserved categories were, at some point, affected. J.P.'s
      unusual deficit supports the hypothesis that semantic knowledge is organized in
      the brain on the basis of object properties, which can cut across the living
      nonliving categorical distinction.

PMID- 14599277
TI  - Effect of the fragile X status categories and the fragile X mental retardation
      protein levels on executive functioning in males and females with fragile X.
AB  - The effects of a fragile X disorder on executive function impairment were
      assessed in 144 extended families, which included individuals with fragile X
      premutation and full mutation and their relatives without fragile X. A
      modification of the maximum-likelihood estimators for pedigree data, as well as
      ordinal logistic regression, were used in data analysis. The most outstanding
      deficit, occurring especially in males, involved impaired capacity to use an
      intention to regulate purposeful behavior. This deficit occurred independently of
      general cognitive impairment but was related to depletion of fragile X mental
      retardation 1 gene protein product. The other executive function deficits were
      accounted for by the general cognitive impairment. Possible mechanisms of the
      effect of fragile X premutation on impairments of executive functioning are
      considered.

PMID- 14599278
TI  - Neural basis for verb processing in Alzheimer's disease: an fMRI study.
AB  - Patients with probable Alzheimer's disease (AD) have difficulty understanding
      verbs. To investigate the neural basis for this deficit, the authors used
      functional magnetic resonance imaging to examine patterns of neural activation
      during verb processing in 11 AD patients compared with 16 healthy seniors.
      Subjects judged the pleasantness of verbs, including MOTION verbs and COGNITION
      verbs. Healthy seniors and AD patients both activated posterolateral temporal and
      inferior frontal regions during judgments of verbs. These activations were
      relatively reduced and somewhat changed in their anatomic distribution in AD
      patients compared with healthy seniors, particularly for the subcategory of
      MOTION verbs, but AD patients showed minimal activation in association with
      COGNITION verbs. These findings imply that poor performance with verbs in AD is
      due in part to altered activation of the large-scale neural network that supports
      verb processing.

PMID- 14599279
TI  - Developmental dynamics: toward a biologically plausible evolutionary psychology.
AB  - There has been a conceptual revolution in the biological sciences over the past
      several decades. Evidence from genetics, embryology, and developmental biology
      has converged to offer a more epigenetic, contingent, and dynamic view of how
      organisms develop. Despite these advances, arguments for the heuristic value of a
      gene-centered, predeterministic approach to the study of human behavior and
      development have become increasingly evident in the psychological sciences during
      this time. In this article, the authors review recent advances in genetics,
      embryology, and developmental biology that have transformed contemporary
      developmental and evolutionary theory and explore how these advances challenge
      gene-centered explanations of human behavior that ignore the complex, highly
      coordinated system of regulatory dynamics involved in development and evolution.

PMID- 14599280
TI  - Evolutionary psychology from a developmental systems perspective: comment on
      Lickliter and Honeycutt (2003).
AB  - Although agreeing with R. Lickliter and H. Honeycutt (2003) that evolutionary
      psychology lacks and should adopt a coherent developmental model to explain how
      evolved mechanisms become expressed in phenotypes, it is argued that adhering to
      the principles of developmental systems theory, despite enhancing evolutionary
      psychology, would not change appreciably its basic focus. The concepts of
      innateness and modularity, what is inherited and what evolves, as well as the
      possible role of developmental plasticity in the evolution of human cognition are
      discussed. It is proposed that evolutionary psychology can incorporate the
      developmental systems perspective into its theorizing, with the end result being
      a science that more closely reflects human nature.

PMID- 14599281
TI  - Fictions and facts about evolutionary approaches to human behavior: comment on
      Lickliter and Honeycutt (2003).
AB  - Six misconceptions about evolutionary approaches to human behavior are exposed.
      Evidence is adduced to support the assertions that evolutionary approaches do not
      (a) adopt a reductionistic "gene-centered" level of analysis, (b) assume that
      natural selection is the only process that creates and designs ontogenetic
      processes and phenotypic outcomes, (c) assume that genes are the only agents
      responsible for the transgenerational inheritance of phenotypic traits and
      characteristics, (d) assume that genes are self-contained and impervious to
      extragenetic influences, (e) posit a strong form of genetic determinism, or (f)
      pay lip service to the role of the environment. Building straw men and knocking
      them down is an inherently destructive enterprise; integrating different
      approaches is a more constructive way of contributing to the growth of knowledge.

PMID- 14599282
TI  - Evolutionary psychology and developmental dynamics: comment on Lickliter and
      Honeycutt (2003).
AB  - Evolutionary psychology provides a cogent metatheory for psychological science.
      It has furnished compelling theories of major domains of human functioning,
      including mating, parenting, kinship, morality, cooperation, conflict,
      aggression, and aesthetics. It has produced hundreds of empirical discoveries
      missed entirely by prior psychologists. Developmental dynamics, properly
      conceived, can add to the theoretical foundation of evolutionary psychology. But
      it has not provided alternative theories capable of explaining the many detailed
      empirical discoveries made by evolutionary' psychologists. Nor has it generated a
      comparable bounty of new empirical discoveries. By critical scientific standards-
      theoretical cogency, predictive accuracy, interdisciplinary consistency, and
      empirical harvest--modern evolutionary psychology fares well compared with
      alternatives.

PMID- 14599283
TI  - A prolegomenon for a viable evolutionary psychology--the myth and the reality:
      comment on Lickliter and Honeycutt (2003).
AB  - R. Lickliter and H. Honeycutt (2003) attempted to create a dynamic developmental
      systems theory of evolutionary psychology. In this commentary, the author argues
      that the quality of their reasoning, their conflation of evolution and evolution
      by natural selection, their failure to explain the relative importance of
      multilevel, epigenetic interactions, their lack of population thinking, and their
      failure to define adaptation undermines their endeavor.

PMID- 14599284
TI  - The second law of thermodynamics is the first law of psychology: evolutionary
      developmental psychology and the theory of tandem, coordinated inheritances:
      comment on Lickliter and Honeycutt (2003).
AB  - Organisms inherit a set of environmental regularities as well as genes, and these
      two inheritances repeatedly encounter each other across generations. This
      repetition drives natural selection to coordinate the interplay of stably
      replicated genes with stably persisting environmental regularities, so that this
      web of interactions produces the reliable development of a functionally organized
      design. Selection is the only known counterweight to the tendency of physical
      systems to lose rather than grow functional organization. This means that the
      individually unique and unpredictable factors in the web of developmental
      interactions are a disordering threat to normal development. Selection built anti
      entropic mechanisms into organisms to orchestrate transactions with environments
      so that they have some chance of being organization-building and reproduction
      enhancing rather than disordering.

PMID- 14599285
TI  - Developmental dynamics and contemporary evolutionary psychology: status quo or
      irreconcilable views? Reply to Bjorklund (2003), Krebs (2003), Buss and Reeve
      (2003), Crawford (2003), and Tooby et Al. (2003).
AB  - The authors address commentaries by D. F. Bjorklund (2003); D. M. Buss and H. K.
      Reeve (2003); C. B. Crawford (2003); D. L. Krebs (2003); and J. Tooby, L.
      Cosmides, and H. C. Barrett (2003) on their analysis of the underlying
      assumptions of contemporary evolutionary psychology (R. Lickliter & H. Honeycutt,
      2003). The authors argue that evolutionary psychology currently offers no
      coherent framework for how to integrate genetic, environmental, and experiential
      factors into a theory of behavioral or cognitive phenotypes. The authors propose
      that this absence is due to a lack of developmental analysis in the major works
      of evolutionary psychology, resulting in an almost exclusive focus on
      adaptationist accounts of evolution by natural selection rather than a more broad
      based focus on the process and products of evolution by epigenetic developmental
      dynamics.

PMID- 14599286
TI  - Effects of the presence of others on food intake: a normative interpretation.
AB  - The authors review the effect of the presence of others on food intake. In social
      facilitation studies, people tend to eat more in groups than when alone. In
      modeling studies, the presence of others may facilitate or inhibit intake,
      depending on how much these other people eat. Studies of impression management
      demonstrate that people tend to eat less in the presence of others than when
      alone. The authors attempt to reconcile these divergent literatures by reference
      to a model of inhibitory norms that govern eating. In the presence of palatable
      food, and in the absence of clear signals of satiety, people look outward to cues
      from the environment to determine when to stop eating. Socially derived
      inhibitory norms can account for either increased or decreased intake in the
      presence of others, depending on how much the others eat and the extent to which
      one is eager to impress them.

PMID- 14599287
TI  - The social risk hypothesis of depressed mood: evolutionary, psychosocial, and
      neurobiological perspectives.
AB  - The authors hypothesize that depressed states evolved to minimize risk in social
      interactions in which individuals perceive that the ratio of their social value
      to others, and their social burden on others, is at a critically low level. When
      this ratio reaches a point where social value and social burden are approaching
      equivalence, the individual is in danger of exclusion from social contexts that,
      over the course of evolution, have been critical to fitness. Many features of
      depressed states can be understood in relation to mechanisms that reduce social
      risk in such circumstances, including (a) hyper-sensitivity to signals of social
      threat from others, (b) sending signals to others that reduce social risks, and
      (c) inhibiting risk-seeking (e.g., confident, acquisitive) behaviors. These
      features are discussed in terms of psychosocial and neurobiological research on
      depressive phenomena.

PMID- 14599288
TI  - The affective underpinnings of job perceptions and attitudes: a meta-analytic
      review and integration.
AB  - Using psychometric meta-analysis, the authors present a quantitative and
      qualitative review (k = 205, total pairwise N = 62,527) of the literature
      relating trait and state positive affect (PA) and negative affect (NA) to job
      related attitudes, including job satisfaction, organizational commitment,
      turnover intentions, and dimensions of job burnout. Results indicated substantial
      correlations, ranging in absolute value from -.17 (PA and turnover intentions; NA
      and personal accomplishment) to.54 (NA and emotional exhaustion). Correlational
      results largely were consistent across hypothesized and exploratory moderator
      conditions. Meta-analytic multiple regression results generally supported the
      unique contribution of each affect to each attitude variable of interest.
      Implications and suggestions for future research on emotion-related aspects of
      job attitudes are discussed.

PMID- 14599289
TI  - Is caregiving hazardous to one's physical health? A meta-analysis.
AB  - Caring for a family member with dementia is generally regarded as a chronically
      stressful process, with potentially negative physical health consequences.
      However, no quantitative analysis has been conducted on this literature. The
      authors combined the results of 23 studies to compare the physical health of
      caregivers with demographically similar noncaregivers. When examined across 11
      health categories, caregivers exhibited a slightly greater risk for health
      problems than did noncaregivers. However, sex and the health category assessed
      moderated this relationship. Stronger relationships occurred with stress
      hormones, antibodies, and global reported health. The authors argue that a
      theoretical model is needed that relates caregiver stressors to illness and
      proffers moderating roles for vulnerabilities and resources and mediating roles
      for psychosocial distress and health behaviors.

PMID- 14599290
TI  - AlphaII-spectrin is an in vitro target for caspase-2, and its cleavage is
      regulated by calmodulin binding.
AB  - The spectrin-actin scaffold underlying the lipid bilayer is considered to
      participate in cell-shape stabilization and in the organization of specialized
      membrane subdomains. These structures are dynamic and likely to undergo frequent
      remodelling during changes in cell shape. Proteolysis of spectrin, which occurs
      during apoptosis, leads to destabilization of the scaffold. It is also one of the
      major processes involved in membrane remodelling. Spectrins, the main components
      of the membrane skeleton, are the targets for two important protease systems: m-
      and micro-calpains (Ca2+-activated proteases) and caspase-3 (activated during
      apoptosis). In this paper, we show that caspase-2 also targets spectrin in vitro,
      and we characterize Ca2+/calmodulin-dependent regulation of spectrin cleavage by
      caspases. Yeast two-hybrid screening reveals that the large isoform (1/L) of
      procaspase-2 specifically binds to alphaII-spectrin, while the short isoform does
      not. Like caspase-3, caspase-2 cleaves alphaII-spectrin in vitro at residue Asp
      1185. This study emphasizes a role of executioner caspase for caspase-2. We also
      demonstrated that the executioner caspase-7 but not caspase-6 cleaves spectrin at
      residue Asp-1185 in vitro. This spectrin cleavage by caspases 2, 3 and 7 is
      inhibited by the Ca2+-dependent binding of calmodulin to spectrin. In contrast,
      calmodulin binding enhances spectrin cleavage by calpain at residue Tyr-1176.
      These results indicate that alphaII-spectrin cleavage is highly influenced by
      Ca2+ homoeostasis and calmodulin, which therefore represent potential regulators
      of the stability and the plasticity of the spectrin-based skeleton.

PMID- 14599291
TI  - BmTx3, a scorpion toxin with two putative functional faces separately active on A
      type K+ and HERG currents.
AB  - A novel HERG channel blocker was isolated from the venom of the scorpion Buthus
      martensi Karsch, sequenced and characterized at the pharmacological level after
      chemical synthesis. According to the determined amino acid sequence, the cDNA and
      genomic genes were then cloned. The genomic gene consists of two exons
      interrupted by an intron of 65 bp at position -6 upstream from the mature toxin.
      The protein sequence of this toxin was completely identical with that of a known
      A-type K+ current blocker BmTx3, belonging to scorpion alpha-KTx subfamily 15.
      Thus BmTx3 is the first reported alpha-KTx peptide also showing HERG-blocking
      activity, like gamma-KTx peptides. Moreover, different from classical alpha-KTx
      peptides, such as charybdotoxin, BmTx3 cannot block Shaker -type K+ channels.
      Phylogenetic tree analysis reveals that this toxin takes an intermediate position
      between classical alpha-KTx and gamma-KTx toxins. From a structural point of
      view, we propose that two separate functional faces might exist on the BmTx3
      molecule, responsible for the two different K+-current-blocking functions. Face
      A, composed of Arg18 and Lys19 in the alpha-helix side, might correspond to HERG
      blocking activity, whereas Face B, containing a putative functional dyad (Lys27
      and Tyr36) in the beta-sheet side, might correspond to A-type blocking activity.
      A specific deletion mutant with the disrupted Face B, BmTx3-Y36P37del, loses the
      A-type current-blocking activity, but keeps a similar HERG-blocking activity, as
      seen with the wild-type toxin.

PMID- 14599293
TI  - Membrane and raft association of reggie-1/flotillin-2: role of myristoylation,
      palmitoylation and oligomerization and induction of filopodia by overexpression.
AB  - The reggie protein family consists of two proteins, reggie-1 and -2, also called
      flotillins, which are highly ubiquitous and evolutionarily conserved. Both
      reggies have been shown to be associated with membrane rafts and are involved in
      various cellular processes such as T-cell activation, phagocytosis and insulin
      signalling. However, the exact molecular function of these proteins remains to be
      determined. In addition, the mechanism of membrane association of reggie-1, which
      does not contain any transmembrane domain, is not known. In this study, we have
      produced a fusion protein of reggie-1 with enhanced green fluorescent protein and
      generated targeted substitutions for the inactivation of putative palmitoylation
      and myristoylation sites. We were able to show that reggie-1 is myristoylated and
      multiply palmitoylated and that lipid modifications are necessary for membrane
      association of reggie-1. Overexpression of reggie-1 resulted in the induction of
      numerous filopodia-like protrusions in various cell lines, suggesting a role for
      reggie-1 as a signalling protein in actin-dependent processes.

PMID- 14599292
TI  - Peroxide-mediated chromatin remodelling of a nuclear factor kappa B site in the
      mouse inducible nitric oxide synthase promoter.
AB  - Hepatocyte expression of iNOS (inducible nitric oxide synthase) and synthesis of
      nitric oxide convey protective antioxidant functions in models of sepsis, shock
      and reperfusion. However, the underlying redox-sensitive mechanisms that regulate
      hepatocyte expression of iNOS and its antioxidant functions are largely unknown.
      Activity of the transcription factor NF-kappaB (nuclear factor kappaB) is known
      to be redox-modulated. In this regard, the mouse hepatocyte iNOS promoter has NF
      kappaB-binding sites at nt -1044 to -1034 and at nt -114 to -104, which are
      considered to be critical for iNOS expression in response to pro-inflammatory
      cytokine stimulation. The relative contribution of these two NF-kappaB-binding
      sites in the mouse iNOS promoter to hepatocyte iNOS promoter activity in the
      context of oxidative stress has not been characterized previously. In addition,
      although the cis - and trans -regulatory factors controlling mouse hepatocyte
      iNOS expression have been well-characterized, the local changes in chromatin
      structure that accompany activation of iNOS gene transcription have not been
      considered. In the present study, we demonstrate that (1) in the absence of
      exogenous oxidative stress, the NF-kappaB site at nt -114 is inactive and (2)
      peroxide-mediated oxidative stress induces hyperacetylation and enhanced
      accessibility of the restriction enzyme to this NF-kappaB region. Our results
      suggest that chromatin structural changes activate this NF-kappaB site and
      increase interleukin-1beta-stimulated iNOS expression in the presence of
      oxidative stress.

PMID- 14599294
TI  - Cytosolic phospholipase A2-p11 interaction controls arachidonic acid release as a
      function of epithelial cell confluence.
AB  - Madin-Darby canine kidney type II cells were shown to release low amounts of AA
      (arachidonic acid) and prostaglandin E2 in response to various stimuli when
      analysed after cell confluence. In contrast, non-confluent Madin-Darby canine
      kidney type II cells released much higher amounts of AA and prostaglandin E2. In
      both stationary and non-confluent cells, AA was released by type IV cPLA2
      (cytosolic phospholipase A2), as shown by the use of specific inhibitors and by
      analysis of the profile of fatty acids released. This confluence-dependent cPLA2
      activation was not due to a difference in expression, or in phosphorylation of
      the enzyme, or in the amount of its substrate. To find out the mechanism by which
      cPLA2 activation may be regulated as a function of cell confluence,
      immunofluorescence and co-immunoprecipitation experiments were performed using
      cPLA2, p11, a natural inhibitor of the enzyme, and annexin II, the natural ligand
      of p11. These three proteins were expressed at a constant level, regardless of
      the cell confluence. In contrast, whereas annexin II and cPLA2 interacted at a
      constant rate, p11 and cPLA2 interacted more strongly in stationary cells, thus
      indicating that cPLA2 activation is regulated by its accessibility to p11,
      independent of their expression level. Our results indicate that, in epithelial
      cells, the cell confluence, i.e. the establishment of cell-cell contacts, rather
      than cell proliferation directly controls cPLA2 activation by changing the
      stoichiometry of p11/cPLA2 interaction.

PMID- 14599295
TI  - Polymorphism in the Plasmodium falciparum chloroquine-resistance transporter
      protein links verapamil enhancement of chloroquine sensitivity with the clinical
      efficacy of amodiaquine.
AB  - BACKGROUND: Chloroquine accumulates in the acidic digestive vacuole of the
      intraerythrocytic malaria parasite, and prevents the detoxication of haematin
      released during haemoglobin digestion. Changes in protein PfCRT in the digestive
      vacuole membrane of growing intra-erythrocytic stages of Plasmodium falciparum
      are crucial for resistance. Expressed in yeast, PfCRT resembles an anion channel.
      Depressed anion channel function could increase intralysosomal pH to reduce entry
      of basic drug, or enhanced function could reduce drug interaction with target
      haematin. The most important resistance-associated change is from positively
      charged lysine-76 to neutral threonine which could facilitate drug efflux through
      a putative channel. It has been proposed that the resistance-reversing effect of
      verapamil is due to hydrophobic binding to the mutated PfCRT protein, and
      replacement of the lost positive charge, which repels the access of 4
      aminoquinoline cations, thus partially restoring sensitivity.
      Desethylamodiaquine, the active metabolite of amodiaquine, which has significant
      activity in chloroquine-resistance, may also act similarly on its own. METHODS:
      Changes in physicochemical parameters in different CQ-resistant PfCRT sequences
      are analysed, and correlations with drug activity on lines transfected with
      different alleles of the pfcrt gene are examined. RESULTS AND CONCLUSIONS: The
      results support the idea that PfCRT is a channel which, in resistant parasites,
      can allow efflux of chloroquine from the digestive vacuole. Activity of the
      chloroquine/verapamil combination and of desethylamodiaquine both correlate with
      the mean hydrophobicity of PfCRT residues 72-76. This may partly explain clinical
      resistance to amodiaquine found in the first chloroquine-resistant malaria cases
      from South America and enables tentative prediction of amodiaquine's clinical
      activity against novel haplotypes of PfCRT.

PMID- 14599297
TI  - Gefitinib for non-small cell lung cancer: is the efficacy real?

PMID- 14599298
TI  - 14th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics
      Frankfurt, Germany.

PMID- 14599299
TI  - Erlotinib (OSI-774, Tarceva), a selective epidermal growth factor receptor
      tyrosine kinase inhibitor, in combination with chemotherapy for advanced non
      small-cell lung cancer.

PMID- 14599296
TI  - In vivo measurement of bending stiffness in fracture healing.
AB  - BACKGROUND: Measurement of the bending stiffness a healing fracture represents a
      valid variable in the assessment of fracture healing. However, currently
      available methods typically have high measurement errors, even for mild pin
      loosening. Furthermore, these methods cannot provide actual values of bending
      stiffness, which precludes comparisons among individual fractures. Thus, even
      today, little information is available with regards to the fracture healing
      pattern with respect to actual values of bending stiffness. Our goals were,
      therefore: to develop a measurement device that would allow accurate and
      sensitive measurement of bending stiffness, even in the presence of mild pin
      loosening; to describe the course of healing in individual fractures; and help to
      evaluate whether the individual pattern of bending stiffness can be predicted at
      an early stage of healing. METHODS: A new measurement device has been developed
      to precisely measure the bending stiffness of the healing fracture by simulating
      four-point-bending. The system was calibrated on aluminum models and intact
      tibiae. The influence of pin loosening on measurement error was evaluated. The
      system was tested at weekly intervals in an animal experiment to determine the
      actual bending stiffness of the fracture. Transverse fractures were created in
      the right tibia of twelve sheep, and then stabilized with an external fixator. At
      ten weeks, bending stiffness of the tibiae were determined in a four-point
      bending test device to validate the in-vivo-measurement data. RESULTS: In-vivo
      bending stiffness can be measured accurately and sensitive, even in the early
      phase of callus healing. Up to a bending stiffness of 10 Nm/degree, measurement
      error was below 3.4% for one pin loose, and below 29.3% for four pins loose,
      respectively. Measurement of stiffness data over time revealed a significant
      logarithmic increase between the third and seventh weeks, whereby the logarithmic
      rate of change among sheep was similar, but started from different levels.
      Comparative measurements showed that early individual changes between the third
      and fourth weeks can be used as a predictor of bending stiffness at seven weeks
      (r = 0.928) and at ten weeks (r = 0.710). CONCLUSION: Bending stiffness can be
      measured precisely, with less error in the case of pin loosening. Prediction of
      the future healing course of the individual fracture can be assessed by changes
      from the third to the fourth week, with differences in stiffness levels.
      Therefore, the initial status of the fracture seems to have a high impact on the
      individual healing course.

PMID- 14599300
TI  - Radiation dose intensification in limited-stage small-cell lung cancer.
AB  - Multiple studies have confirmed the value of radiation therapy in limited-stage
      small-cell lung cancer. The appropriate dose of radiation and the optimal
      fractionation scheme, however, remain controversial. This article will examine
      the history of radiation therapy in the management of small-cell lung cancer. It
      will review the rationale for the various approaches to radiation dose
      intensification, and review the results of important trials investigating the
      issue of radiation dose in the management of this disease. Survival outcomes and
      toxicity of various approaches to radiation dose intensification, including dose
      escalation and hyperfractionation, will be assessed. The implications of
      advancements in technology will be examined, and the optimal design of future
      trials will be discussed.

PMID- 14599301
TI  - Role of cyclooxygenase-2 inhibitors in combination with radiation therapy in lung
      cancer.
AB  - Cyclooxygenase-2 (COX-2) is an enzyme involved in prostaglandin production in
      pathologic states such as inflammatory disorders and cancer. The enzyme is often
      overexpressed in premalignant lesions and cancer of the lung. Overexpression of
      COX-2 in lung cancer is associated with more aggressive biological tumor behavior
      and adverse patient outcome. In preclinical studies, inhibition of this enzyme
      with selective COX-2 inhibitors enhances tumor response to radiation and
      chemotherapeutic agents. These findings have been rapidly advanced to clinical
      oncology. Clinical trials of the combination of selective COX-2 inhibitors with
      radiation therapy, chemotherapy, or both in patients with lung cancer have been
      initiated and some preliminary results are available. In this review, we describe
      the relationship between overexpression of COX-2 and lung cancer, the antitumor
      effect of selective COX-2 inhibitors, discuss the rationale for using selective
      COX-2 inhibitors combined with radiation therapy and chemotherapy, and summarize
      current clinical protocols and initial findings.

PMID- 14599302
TI  - Dermatologic side effects associated with gefitinib therapy: clinical experience
      and management.
AB  - Gefitinib (ZD1839, Iressa ), a selective inhibitor of the epidermal growth factor
      receptor-tyrosine kinase, is currently in clinical trials to treat a variety of
      solid tumors. Similar side effects were seen in numerous clinical trials of
      gefitinib, including recent phase II trials (Iressa Dose Evaluation in Advanced
      Lung Cancer [IDEAL]-1 and IDEAL-2) in patients with advanced, previously treated
      non-small-cell lung cancer (NSCLC). The most frequent drug-related adverse
      effects reported in these trials were diarrhea, dry skin, acneiform rash, and
      nausea and vomiting. Recently, IDEAL-2 investigators and oncology nurses
      participated in a panel discussion on the management of dermatologic adverse
      effects associated with gefitinib treatment. These dermatologic effects were
      related to the mechanism of action of gefitinib and were not caused by a drug
      related allergic reaction. In IDEAL-2, investigators managed the symptoms of dry
      skin and rash with a variety of treatments, including topical clindamycin,
      antibiotics, and corticosteroids. Most patients had a high level of tolerance for
      the dermatologic effects associated with gefitinib, which were milder than
      toxicities associated with chemotherapy. The severity of skin effects cycled over
      time during treatment but typically subsided after several weeks of gefitinib
      treatment. In general, dermatologic effects of gefitinib were easily managed,
      reversible, and well tolerated by these patients with advanced NSCLC.

PMID- 14599303
TI  - Gefitinib in the treatment of advanced, refractory non-small-cell lung cancer:
      results in 124 patients.
AB  - To evaluate the feasibility, toxicity, and efficacy of oral gefitinib (ZD1839,
      Iressa) in patients with refractory non-small-cell lung cancer (NSCLC) treated in
      a community-based setting. One hundred twenty-four patients with advanced,
      refractory NSCLC received treatment with gefitinib 250 mg orally each day. Ninety
      six percent of patients had received >or= 1 previous chemotherapy regimens and
      79% had received previous platinum and taxane therapy. Patients were evaluated
      for response after 6-12 weeks of daily gefitinib therapy; patients with objective
      response or stable disease continued gefitinib until disease progression
      occurred. Gefitinib was well-tolerated in these patients with advanced,
      refractory NSCLC. There were no grade 4 toxicities, and grade 3 skin toxicity and
      diarrhea were observed in only 4% and 2% of patients, respectively. Nine of 120
      evaluable patients (8%) had partial responses to treatment; however, 54 patients
      (45%) had no evidence of progression at first reevaluation, and a total of 35
      patients (29%) reported improvement in lung cancer-related symptoms while
      receiving gefitinib. Median survival for the entire group was 6.5 months, with a
      1-year survival rate of 35%. Gefitinib is active and very well-tolerated in
      patients with advanced, refractory NSCLC. Although the major response rate was
      low, nearly 50% of patients derived substantial palliative benefit from gefitinib
      therapy. The median survival of 6.5 months achieved in this large group of
      relatively unselected patients is unprecedented in the third-line treatment
      setting, and compares favorably to other available second-line treatment
      including docetaxel. A therapeutic trial of gefitinib should be considered in all
      patients with refractory NSCLC.

PMID- 14599304
TI  - Refinements in telemetry procedures. Seventh report of the
      BVAAWF/FRAME/RSPCA/UFAW Joint Working Group on Refinement, Part A.

PMID- 14599305
TI  - Male management: Coping with aggression problems in male laboratory mice.
AB  - In a laboratory environment, aggressive interactions between male mice may exceed
      normal levels leading to negative effects both on the well-being of the animals
      and on the validity of experimental results. In this paper we review results from
      the literature and our own research with regard to coping with excessive
      aggressive behaviour in male laboratory mice. Based on this review practical
      recommendations concerning the housing and care of male laboratory mice are
      formulated. In short, it is recommended to avoid individual housing, to transfer
      odour cues from the nesting area during cage cleaning and to apply nesting
      material as environmental enrichment. Furthermore, group size should be optimized
      to three animals per cage. Further research, in particular into the effects of
      frequency, duration, type and severity of disturbances during an experiment on
      the degree of aggression, is recommended.

PMID- 14599306
TI  - Are the effects of different enrichment designs on the physiology and behaviour
      of DBA/2 mice consistent?
AB  - Environmental enrichment is intended to improve the well-being of laboratory
      animals. Although many researchers have indicated that environmental enrichment
      may enhance animal well-being, there is some evidence that enrichment differs in
      its effects on physiology and behaviour between species and strains. The present
      study focuses on the effects of different enrichment designs on the physiology
      and behaviour of male and female DBA/2 mice. A total of 48 DBA/2J mice, 24 males
      and 24 females were used for this experiment. Upon arrival at about 3 weeks of
      age, the animals were randomly allotted to three experimental groups: NE, non
      enrichment; E1, enriched with nest box, wooden climbing bar and nest material
      according to Scharmann (1993); E2, enriched with horizontal and vertical
      dividers, modified from Haemisch and Gartner (1994). Same-sex groups of four mice
      were housed for 12 weeks in type III Makrolon cages with (E1 or E2) or without
      (NE) enrichment objects. Behavioural performance (Open Field, Food Drive and
      Elevated Plus Maze tests) and physiological traits (haematological variables,
      body weight and organ weights, corticosterone and thyroxine levels) were
      measured. This study observed that enrichment had significant effects on the mean
      values of body weight (females), Open Field and Food Drive tests. The most
      significant housing differences were found between the E2 and NE/E1 groups.
      Furthermore, sex differences in the NE, E1 and E2 groups were not consistent for
      several variables (growth rate, relative weights of spleen, kidney and heart,
      Food Drive and Elevated Plus Maze behavioural performance). There was often a
      higher coefficient of variation (CV) in the E1 and E2 groups as compared to the
      NE group, chiefly in physiological traits and in the Open Field and Food Drive
      tests. The results of this study indicate, that the effects of enrichment designs
      used in the present study are not consistent, but vary according to sex and the
      variable studied.

PMID- 14599307
TI  - Effect of enrichment on variation and results in the light/dark test.
AB  - Several confounding factors may influence the outcome of an experiment and the
      extent of inter-individual variation. The aim of this study was to investigate if
      cage enrichment induces an effect on experimental mean values and on inter
      individual variation in the light/dark paradigm using diazepam as the anxiolytic
      drug. The behaviour of 216 naive adult male mice of two different strains (BALB/c
      and C57BL/6) was studied. The animals were housed in groups of four in 'non
      enriched', 'enriched' (nesting material) or 'super-enriched' (nest-box, nesting
      material, wooden gnawing stick and PVC tube) cages. After 5 weeks the animals
      were assigned to one of three treatments: control (no injection), sham (saline
      injection i.p.) or diazepam (1 mg/kg bw i.p.) and tested in the light/dark test
      for 5 min. Variation data were analysed using three different methods (mean
      absolute deviation, coefficient of variation and power analysis). The C57BL/6
      mice scored higher than BALB/c mice in activity related measurements and showed a
      less 'emotional' behaviour profile in the pharmacological control situation of
      the light/dark test. In this study the anxiolytic effect of diazepam was clear in
      BALB/c mice but absent in C57BL/6 mice. Mice housed in enriched and super
      enriched cages gained more weight than mice in non-enriched cages, although food
      intake was not affected. Generally, the strain of mouse had the greatest impact
      on both mean values and variation. However, there was no consistent increase for
      one particular strain. The choice of statistical method for analysing variation
      may influence the interpretation of within-group variability, but none of the
      methods showed any significant differences between standard and enriched
      conditions on variability in any of the parameters measured.

PMID- 14599308
TI  - Detection of Reovirus type 3 by use of fluorogenic nuclease reverse transcriptase
      polymerase chain reaction.
AB  - Reovirus type 3 (Reo-3) can infect numerous rodent species and induces the
      clinical syndrome 'oily skin disease' in neonatal mice, and is a common
      contaminant of biological materials. The reverse transcriptase polymerase chain
      reaction (RT-PCR) assay has proven useful for the detection of Reo-3 in rodents
      and contaminated biological materials. Fluorogenic nuclease reverse transcriptase
      polymerase chain reaction assays (fnRT-PCR) combine RT-PCR with an internal
      fluorogenic hybridization probe, thereby potentially enhancing specificity and
      eliminating post-PCR processing. Therefore, an fnRT-PCR assay specific for Reo-3
      was developed by targeting primer and probe sequences to a unique region of the
      Reo-3 M3 gene. The fnRT-PCR detected both strains of Reo-3 (Dearing and Abney),
      but did not detect Reovirus types 1 or 2, other viruses in the family Reoviridae,
      or other RNA viruses that naturally infect rodents. The fnRT-PCR detected less
      than 1 fg of target template and detected viral RNA in tissues obtained from mice
      experimentally infected with Reo-3. The assay also displayed comparable
      sensitivity when compared to the mouse antibody production test commonly used to
      detect viral contamination of biological materials. In conclusion, this fnRT-PCR
      assay offers a potentially high-throughput diagnostic assay for detecting Reo-3
      RNA in infected mice and contaminated biological materials.

PMID- 14599309
TI  - A miniature self-inflating bag-mask ventilator for rats.
AB  - Respiratory depression and apnoea during anaesthesia may lead to hypoxia and
      myocardial ischaemia. A self-inflating miniature bag-mask device was assembled
      combining characteristics from the Ambu-bag and the Kuhn-system. This bag-mask
      device permitted ventilation during anaesthesia-induced apnoea in rats until a
      safe airway by tracheotomy was achieved.

PMID- 14599310
TI  - Short-term effects of N'N-bis(dichloroacetyl)-1,8-octamethylenediamine (WIN
      18446) on the testes, selected sperm parameters and fertility of male CBA mice.
AB  - N'N-bis(dichloroacetyl)-1,8-octamethylenediamine (WIN 18446), the most potent of
      the diamines and one of the least amoebicidal agents, was shown to exert a
      specific effect on the testes of CBA mice, while the Leydig cells were
      unaffected. Spermatogenesis was severely affected after a 42-day treatment period
      with 125 mg WIN 18446/kg body weight. Large multinucleated cells, vacuolization
      and the absence of sperm within the testes were evident in most seminiferous
      tubules. After 15 days of withdrawal of WIN 18446, there was a slight recovery of
      spermatogenesis and after withdrawal of 42 days a marked recovery of
      spermatogenesis. The normality or abnormality of this spermatogenic cycle could
      be evaluated using the semi-quantitative Stages program. There was a significant
      decrease in the diameters of seminiferous tubules of WIN 18446 treated mice,
      however an almost complete recovery was evident after 42 days of withdrawal of
      WIN 18446. A significant decrease in sperm concentration and sperm morphology was
      observed for the WIN 18446 treated mice. Various sperm motion parameters were
      assessed for the different treatment groups and compared to the control group.
      The female and male fertility indices were assessed and compared for the
      different treatment groups. Complete recovery of the above-mentioned parameters
      was evident after 42 days of withdrawal from WIN 18446, and this confirms its
      potential as a possible contraceptive for animal populations.

PMID- 14599311
TI  - Exploration and high adventure: the legacy of Grey Walter.
AB  - Although many people feel themselves to be familiar with Grey Walter's ideas, and
      with the design principles of his tortoises, most of the published sources are
      lacking in detail. This paper gathers together images and written material from a
      variety of published and unpublished sources to set both the man and his work in
      a richer context than has been possible for many decades. Grey Walter emerges as
      a fascinating and far-seeing figure whose work has not dated, perhaps because it
      was explicitly based on similar principles to those used today in biologically
      inspired robotics.

PMID- 14599312
TI  - Controlled analysis of neurocontrollers with informational lesioning.
AB  - How does one aim to understand neural information processing? One of the
      difficult first challenges is to identify the roles of the network's elements. To
      this end a functional contribution analysis (FCA) method has been developed and
      applied for studying the neurocontrollers of evolutionary autonomous agents
      (EAAs). The FCA processes data composed of multiple lesion experiments and the
      corresponding performance levels that the agent obtains under these lesions. It
      calculates the contribution values (CVs) of the network's elements such that the
      ability to predict the agent's performance under new, unseen lesions is
      maximized. Previous analysis has found a strong dependence of the CVs and the
      prediction error on the specific type of lesioning method used, i.e. on the way
      in which the activity of lesioned neurons is disrupted. We present a new,
      informational lesioning method (ILM), which views a lesion as a noisy channel and
      applies a controlled lesion to the network by varying the lesioning level from
      large to arbitrarily small magnitudes. Studying the ILM within the FCA framework,
      our main results are threefold: first, that lower lesioning levels permit more
      accurate FCA predictions; second, that the usage of minute ILM lesioning levels
      can uncover the long-term effects of elements on the network's functioning; and
      third, that as the lesioning level decreases, the CVs tend to approach limit
      values, reflecting the importance of these elements in the intact, normal
      functioning neurocontroller.

PMID- 14599313
TI  - From biological models to the evolution of robot control systems.
AB  - Attempts to formulate realistic models of the development of the human oculomotor
      control system have led to the conclusion that evolutionary factors play a
      crucial role. Moreover, even rather coarse simulations of the biological
      evolutionary processes result in adaptable control systems that are considerably
      more efficient than those designed by human researchers. In this paper I shall
      describe some of the aspects of these biological models that are likely to be
      useful for building robot control systems. In particular, I shall consider the
      evolution of appropriate innate starting points for learning/adaptation, patterns
      of learning rates that vary across different system components, learning rates
      that vary during the system's lifetime, and the relevance of individual
      differences across the evolved populations.

PMID- 14599314
TI  - Grounding vision through experimental manipulation.
AB  - Experimentation is crucial to human progress at all scales, from society as a
      whole to a young infant in its cradle. It allows us to elicit learning episodes
      suited to our own needs and limitations. This paper develops active strategies
      for a robot to acquire visual experience through simple experimental
      manipulation. The experiments are oriented towards determining what parts of the
      environment are physically coherent--that is, which parts will move together, and
      which are more or less independent. We argue that following causal chains of
      events out from the robot's body into the environment allows for a very natural
      developmental progression of visual competence, and relate this idea to results
      in neuroscience.

PMID- 14599315
TI  - Developmental robotics: manifesto and application.
AB  - We argue that all embodied organisms, whether robots or animals, face the same
      challenge: of adapting to bodies, brains and environments that undergo constant
      and inevitable change. After highlighting the evidence for the universal role of
      a class of molecular factors called neurotrophic factors in the response of
      animals to this challenge, we suggest that implementing models of neurotrophic
      interactions on robots may confer on them the adaptability and robustness
      exhibited by animals. We briefly review a mathematical model of neurotrophic
      interactions and then discuss its application in a robotic context. Finally, we
      examine the potential, or otherwise, of our approach to developmental robotics.

PMID- 14599316
TI  - Oscillators and crank turning: exploiting natural dynamics with a humanoid robot
      arm.
AB  - This paper presents an approach to robot-arm control that exploits the natural
      dynamics of the arm. This is in contrast to traditional approaches, which either
      ignore or cancel out arm dynamics. While the traditional approaches are more
      general, they often result in systems and robot designs that are not robust. The
      alternative approach gives systems that are computationally simple, robust to
      variation in system parameters, robust to changes in the dynamics themselves, and
      versatile. The approach is examined using the example of a compliant robot arm,
      controlled by independent neural oscillators, in a crank-turning task. A model is
      constructed, and the robot behaviour compared with the model. These data show
      that the arm-oscillator system is exploiting the natural dynamics by finding and
      exciting the resonant mode of the underlying mechanical system. Since this is a
      natural behaviour of the system, the robot behaviour is robust. The paper
      concludes by discussing the opportunities and limitations of this approach.

PMID- 14599317
TI  - Isotropic-sequence-order learning in a closed-loop behavioural system.
AB  - The simplest form of sensor-motor control is obtained with a reflex. In this case
      the reflex can be interpreted as part of a closed-loop control paradigm which
      measures a sensor input and generates a motor reaction as soon as the sensor
      signal deviates from its desired (resting) state. This is a typical case of
      feedback control. However, reflex reactions are tardy, because they occur always
      only after a (for example, unpleasant) reflex-eliciting sensor event. This
      defines an objective problem for an organism which can only be avoided if the
      corresponding motor reaction is generated earlier. The goal of this study is to
      design a closed-loop control situation where temporal-sequence learning
      supersedes a tardy reflex reaction with a proactive anticipatory action. We
      achieve this by employing a second, earlier-occurring and causally coupled sensor
      event. An appropriate motor reaction to this early event prevents triggering of
      the original, primary reflex. Such causally coupled sensor events are common for
      animals, for example when smell predicts taste or when heat radiation precedes
      pain. We show that trying to achieve anticipatory control is a fundamentally
      different goal from trying to model a classical conditioning paradigm, which is
      an open-loop condition. To this end, we use a novel learning rule for temporal
      sequence learning called isotropic-sequence-order (ISO) learning, which performs
      a confounded correlation between the primary sensor signal associated to the
      reflex and a predictive, earlier-occurring sensor input: this way the system
      learns the relation between the primary reflex and the earlier sensor input in
      order to create an earlier-occurring motor reaction. As a consequence of
      learning, the primary reflex will not be triggered any more, thereby permanently
      remaining in its desired resting state. In a robot application, we demonstrate
      that ISO learning can successfully solve the classical obstacle-avoidance task by
      learning to correlate a built-in reflex behaviour (retraction after touching)
      with earlier arising signals from range finders (before touching). Finally, we
      show that avoidance and attraction tasks can be combined in the same agent.

PMID- 14599319
TI  - A test bed for insect-inspired robotic control.
AB  - Flying insects are remarkable examples of sophisticated sensory-motor control
      systems. Insects have solved the fundamental challenge facing the field of mobile
      robots: robust sensory-motor mapping. Control models based on insects can
      contribute much to the design of robotic control systems. We present our work on
      a preliminary robotic control system inspired by current behavioural and
      physiological models of the fruit fly, Drosophila melanogaster. We designed a
      five-degrees-of-freedom robotic system that serves as a novel simulation/mobile
      robot hybrid. This design has allowed us to implement a fly-inspired control
      system that uses visual and mechanosensory feedback. Our results suggest that a
      simple control scheme can yield surprisingly robust fly-like robotic behaviour.

PMID- 14599318
TI  - New neural circuits for robot phonotaxis.
AB  - W. Grey Walter built robotic systems to improve understanding of biological
      systems. In that tradition, this paper reports ongoing work on a robot model of
      cricket sound localization. The main advances are the inclusion of a much larger
      range of neuroethological detail, and the investigation of multimodal influences
      on the behaviour. The former allows exploration of the functionality of
      identified neurons in the insect, including the possible roles of multiple
      sensory fibres, mutually inhibitory connections, and brain neurons with pattern
      filtering properties. The latter focuses on the inclusion of an optomotor
      stabilization response, and how this might improve tracking, particularly under
      conditions of random disturbance.

PMID- 14599320
TI  - Bio-inspired solutions for locomotion in the gastrointestinal tract: background
      and perspectives.
AB  - This paper illustrates a bio-inspired approach to effective, smooth and safe
      navigation in the human body and, in particular, in the gastrointestinal tract.
      This idea originates from the medical need to develop more powerful tools for
      microendoscopy, which is one of the most challenging frontiers of modern
      medicine. Understanding motion and perception systems of lower animal forms, such
      as parasites, worms, insects and snakes, can help to design and fabricate bio
      inspired robots able to navigate in tortuous, slippery and difficult-to-access
      cavities of the human body. A preliminary study of a biomimetic adhesion system
      for the human tissues is presented in this work and some technological
      implementations are illustrated and discussed. Finally, some issues concerning
      the goals of smart and reactive locomotion are considered and the most promising
      and relevant enabling technologies are discussed.

PMID- 14599321
TI  - Evolving spike-timing-dependent plasticity for single-trial learning in robots.
AB  - Single-trial learning is studied in an evolved robot model of synaptic spike
      timing-dependent plasticity (STDP). Robots must perform positive phototaxis but
      must learn to perform negative phototaxis in the presence of a short-lived
      aversive sound stimulus. STDP acts at the millisecond range and depends
      asymmetrically on the relative timing of pre- and post-synaptic spikes. Although
      it has been involved in learning models of input prediction, these models require
      the iterated presentation of the input pattern, and it is hard to see how this
      mechanism could sustain single-trial learning over a time-scale of tens of
      seconds. An incremental evolutionary approach is used to answer this question.
      The evolved robots succeed in learning the appropriate behaviour, but learning
      does not depend on achieving the right synaptic configuration but rather the
      right pattern of neural activity. Robot performance during positive phototaxis is
      quite robust to loss of spike-timing information, but in contrast, this loss is
      catastrophic for learning negative phototaxis where entrained firing is common.
      Tests show that the final weight configuration carries no information about
      whether a robot is performing one behaviour or the other. Fixing weights,
      however, has the effect of degrading performance, thus demonstrating that
      plasticity is used to sustain the neural activity corresponding both to the
      normal phototaxis condition and to the learned behaviour. The implications and
      limitations of this result are discussed.

PMID- 14599322
TI  - Evolving controllers for a homogeneous system of physical robots: structured
      cooperation with minimal sensors.
AB  - We report on recent work in which we employed artificial evolution to design
      neural network controllers for small, homogeneous teams of mobile autonomous
      robots. The robots were evolved to perform a formation-movement task from random
      starting positions, equipped only with infrared sensors. The dual constraints of
      homogeneity and minimal sensors make this a non-trivial task. We describe the
      behaviour of a successful system in which robots adopt and maintain functionally
      distinct roles in order to achieve the task. We believe this to be the first
      example of the use of artificial evolution to design coordinated, cooperative
      behaviour for real robots.

PMID- 14599323
TI  - Rana computatrix to human language: towards a computational neuroethology of
      language evolution.
AB  - Walter's Machina speculatrix inspired the name Rana computatrix for a family of
      models of visuomotor coordination in the frog, which contributed to the
      development of computational neuroethology. We offer here an 'evolutionary'
      perspective on models in the same tradition for rat, monkey and human. For rat,
      we show how the frog-like taxon affordance model provides a basis for the spatial
      navigation mechanisms that involve the hippocampus and other brain regions. For
      monkey, we recall two models of neural mechanisms for visuomotor coordination.
      The first, for saccades, shows how interactions between the parietal and frontal
      cortex augment superior colliculus seen as the homologue of frog tectum. The
      second, for grasping, continues the theme of parieto-frontal interactions,
      linking parietal affordances to motor schemas in premotor cortex. It further
      emphasizes the mirror system for grasping, in which neurons are active both when
      the monkey executes a specific grasp and when it observes a similar grasp
      executed by others. The model of human-brain mechanisms is based on the mirror
      system hypothesis of the evolution of the language-ready brain, which sees the
      human Broca's area as an evolved extension of the mirror system for grasping.

PMID- 14599324
TI  - Intelligence with representation.
AB  - Behaviour-based robotics has always been inspired by earlier cybernetics work
      such as that of W. Grey Walter. It emphasizes that intelligence can be achieved
      without the kinds of representations common in symbolic AI systems. The paper
      argues that such representations might indeed not be needed for many aspects of
      sensory-motor intelligence but become a crucial issue when bootstrapping to
      higher levels of cognition. It proposes a scenario in the form of evolutionary
      language games by which embodied agents develop situated grounded representations
      adapted to their needs and the conventions emerging in the population.

PMID- 14599325
TI  - The emergence of communication in evolutionary robots.
AB  - Evolutionary robotics is a biologically inspired approach to robotics that is
      advantageous to studying the evolution of communication. A new model for the
      emergence of communication is developed and tested through various simulation
      experiments. In the first simulation, the emergence of simple signalling
      behaviour is studied. This is used to investigate the inter-relationships between
      communication abilities, namely linguistic production and comprehension, and
      other behavioural skills. The model supports the hypothesis that the ability to
      form categories from direct interaction with an environment constitutes the
      grounds for subsequent evolution of communication and language. In the second
      simulation, evolutionary robots are used to study the emergence of simple
      syntactic categories, e.g. action names (verbs). Comparisons between the two
      simulations indicate that the signalling lexicon emerged in the first simulation
      follows the evolutionary pattern of nouns, as observed in related models on the
      evolution of syntactic categories. Results also support the language-origin
      hypothesis on the fact that nouns precede verbs in both phylogenesis and
      ontogenesis. Further extensions of this new evolutionary robotic model for
      testing hypotheses on language origins are also discussed.

PMID- 14599326
TI  - The reliability of diagnosis using store-and-forward teledermatology.
AB  - We compared diagnoses made by a teledermatologist from digital photographs and
      patient histories sent from general practitioners using a store-and-forward
      technique and those made by another dermatologist in a face-to-face consultation
      with the same patients. A total of 117 patients (mean age 47 years) were referred
      by 18 general practitioners for diagnosis of a skin condition. Between one and
      seven digital images were transmitted per case. In 31% of the cases, three images
      were transmitted. There was full concordance between store-and-forward and face
      to-face diagnoses in 57 of 106 cases (54%); in 10 cases (9%) there was overlap
      between the differential diagnoses provided by the teledermatologist and the face
      to-face consultant. Diagnostic categories with relatively high concordances were
      eczema and follicular eruptions. General practitioners need to be trained in the
      making of digital images and in giving a good patient history.

PMID- 14599327
TI  - Feasibility and outcome evaluation of a telemedicine application in speech
      language pathology.
AB  - This evaluative study assessed the feasibility and outcome of delivering speech
      language services from a distance to children and adolescents who stutter. All
      six patients who formed the first cohort seen in the telespeech programme were
      included in the study. The results demonstrated that interactive
      videoconferencing can provide a feasible and effective care delivery model.
      Patient attendance was maintained throughout the intervention. All participants
      showed improved fluency. Stuttering ranged from 13% to 36% before treatment and
      2% to 26% after treatment. All participants maintained at least part of their
      improved fluency during the six-month follow-up, when stuttering ranged from 4%
      to 32%. The study demonstrates that full assessment and treatment of stuttering
      in children and adolescents can be accomplished successfully via telemedicine.

PMID- 14599328
TI  - A study of a rural community's readiness for telehealth.
AB  - A qualitative approach was used to explore the readiness of a rural community for
      the implementation of telehealth services. There were four domains of interest:
      patient, practitioner, public and organization. Sixteen semistructured telephone
      interviews (three to five in each domain) were carried out with key informants
      and recorded on audio-tape. Two community awareness sessions were held, which
      were followed by five audio-taped focus groups (with five to eight people in
      each) in the practitioner, patient and public domains. In addition, two in-depth
      interviews were conducted with community physicians. Analysis of the data
      suggested that there were four types of community readiness: core, engagement,
      structural and non-readiness. The level of readiness varied across domains. There
      were six main themes: core readiness; structural readiness; projection of
      benefits; assessment of risk; awareness and education; and intra-group and inter
      group dynamics. The results of the study can be used to investigate the readiness
      of rural and remote communities for telehealth, which should improve the chance
      of successful implementation.

PMID- 14599329
TI  - A model of the willingness to use telemedicine for routine and specialized care.
AB  - We examined factors associated with the willingness to use telemedicine for
      routine and specialized care within a theoretical framework. The conceptual model
      proposed that willingness to use telemedicine is associated directly with
      attitudes to telemedicine, attitudes to the patient-physician relationship, and
      to satisfaction with current health-care. In addition, technology anxiety and
      past behaviour were both assumed to affect willingness to use telemedicine
      indirectly. Telephone interviews were conducted with a national sample of 1204
      Jewish, non-institutionalized adults in Israel. Structural equation modelling was
      used to examine the hypothesized relationships. Participants were more willing to
      use telemedicine for routine than for specialized care. Overall, willingness to
      use telemedicine was affected by attitudes to telemedicine, attitudes to the
      patient-physician relationship and by level of technology anxiety. Educational
      interventions aimed at encouraging the use of telemedicine should target
      potential users' attitudes, as well as feelings of uneasiness and anxiety
      regarding technology.

PMID- 14599330
TI  - Acceptance of telemedicine and new media: a survey of Austrian medical students.
AB  - Telemedicine and new media (e.g. the Internet, tele-teaching and tele-learning)
      are increasingly being used in medicine. We surveyed the awareness and acceptance
      of these developments on the part of medical students (n =750) at the University
      of Innsbruck. A 16-item questionnaire was handed out in randomly chosen medical
      classes and collected immediately after completion, which resulted in a response
      rate of 99.9%. Nearly all of the students used the Internet regularly (68%) or at
      least sometimes (30%). Telemedicine was already known to most of the students,
      mainly from articles in magazines and newspapers (41%), but the great majority of
      them (95%) reported that they did not know about the telemedicine lectures
      offered by the University of Innsbruck. Most students (75%) thought that they
      would benefit from tele-teaching or tele-learning. The survey suggested that
      medical schools should offer more special lectures, as well as undergraduate or
      postgraduate qualifications in telemedicine. The marketing of such opportunities
      needs to be improved.

PMID- 14599331
TI  - Feasibility of and satisfaction with the use of low-bandwidth videoconferencing
      for examination of undergraduate students.
AB  - We investigated the feasibility and students' acceptance of Internet-based
      videoconferencing as a communications method during examinations. Thirty-nine
      second-year dental students took an interactive examination in periodontology,
      comprising self-assessment, essay writing, discussion and feedback. The students
      were randomly divided into two groups, which were examined through the standard
      classroom procedure (n =15) or through Internet-based videoconferencing (n =24).
      Students evaluated the experience using a standardized questionnaire. The
      technology proved to be reliable. The interactive examination technique was well
      accepted, although there was significantly less satisfaction in the
      videoconference group (P <0.01). There were no significant differences in the
      performance of students between the two modalities. Interaction was stressed as
      one of the major strengths of the examination by students in the conventional
      group, but it appeared to be less appreciated by the videoconference group.
      Internet-based videoconferencing can successfully facilitate a highly structured
      assessment, although students seem to prefer classroom assessment.

PMID- 14599332
TI  - Experiences of rural women with breast cancer receiving social support via
      audioconferencing.
AB  - We examined the process of social support for breast cancer survivors in rural
      Newfoundland and Labrador. The subjects were 11 participants in a social support
      programme that made use of audioconferencing. The core social psychological
      process by which women received social support consisted of four distinct but
      overlapping stages: getting connected to the network; finding a voice; connecting
      with others; and becoming empowered. The findings suggested that support groups
      facilitated via audioconferencing can transcend geographical distance and permit
      women living in rural areas to share experiences with each other and to learn
      from and teach each other. The use of telephone and audioconferencing
      technologies should be encouraged for the provision of information and support to
      people in rural settings, where such services may be especially beneficial.

PMID- 14599333
TI  - A cost study of prenatal telemedicine.
AB  - We calculated the cost of using a telemedicine system for the cardiotocographic
      (CTG) recording of fetal heart rate. In a one-year study in the Campania region
      of Italy, 162 patients were monitored. The total cost of the telemedicine system
      was euro;344796. A control group was retrospectively drawn from all deliveries at
      the university hospital in Naples during the year 2000. Patients were
      retrospectively assigned to a category of high or low risk, and the hospital
      costs of the high-risk patients were compared. In the intervention group, 11 of
      the 87 high-risk patients (13%) were admitted to hospital prematurely, and stayed
      on average 12 days. In the control group, 203 of the 813 women in the high-risk
      group (25%) were admitted to hospital prematurely, and stayed on average 20 days.
      If the women in the control group had been monitored, there would have been a
      notional saving, through avoided bed days, amounting to 358280, which was similar
      to the cost of the telemedicine system. The study suggests that the use of
      telemedicine in CTG monitoring improves the quality of prenatal care.

PMID- 14599334
TI  - Preliminary clinical evaluation of a video transmission system for home visits.
AB  - A portable video transmission system based on a hand-held computer and cellular
      telephone was developed for use with patients undergoing rehabilitation at home.
      It was designed to be simple to operate, for use by nurses on home care visits.
      The whole system can be held in one hand, and video pictures can be recorded and
      transmitted with the touch of a few buttons. The quality of the transmitted
      pictures and the feasibility of the system were clinically evaluated by physical
      therapists and nurses. Three image transmission scenes were used to evaluate the
      system: turning over in bed; walking; and raising and lowering a shoulder. Nurses
      reported that the system was easy to carry and simple to use. Physiotherapists
      found the system to be useful in making a judgement about the patient's
      condition. The patients were all enthusiastic about the system. The increased
      interaction had the effect of improving the patients' desire to continue their in
      home rehabilitation.

PMID- 14599335
TI  - Tele-ophthalmology and conventional ophthalmology using a mobile medical unit in
      remote Greece.
AB  - We evaluated the quality of medical services delivered to remote glaucoma
      patients from a mobile unit. A four-wheel-drive vehicle containing the necessary
      equipment visited five different remote locations in Greece. During a three-year
      prospective study, 1205 patients were examined, of whom 230 had glaucoma. The
      majority of the subjects were examined by the unit's medical staff using the
      available instrumentation (e.g. slit-lamp and tonometer), while 56 glaucoma
      subjects were telemedically examined by consultants at the Patissia General
      Hospital, in Athens. Control data were obtained from a random sample of 260 urban
      glaucoma patients. A significantly greater proportion of the remote patients had
      an inadequate awareness of glaucoma (77%) compared with the urban patients (20%).
      Significantly more remote patients had poorer compliance (68%) in comparison with
      urban patients (23%). A significantly larger proportion of the remote patients
      had high intra-ocular pressure (21%) compared with the urban patients (5%).
      Technical difficulties occurred in the 13 of the 56 telemedical examinations.
      Mobile medical units can enhance access to medical services and contribute to the
      health-care of under-served populations.

PMID- 14599336
TI  - Comparative study of telecommunication methods for emergency telemedicine.

PMID- 14599337
TI  - A focus tool as an aid to video-otoscopy.

PMID- 14599338
TI  - A mixed learning technology strategy for providing continuing medical education
      to rural physicians.

PMID- 14599339
TI  - Telemedicine reduces referral of diabetic patients to ophthalmologists.

PMID- 14599340
TI  - Redox properties of myeloperoxidase.
AB  - The heme-containing enzyme myeloperoxidase (MPO) is secreted from
      polymorphonuclear leukocytes and monocytes. It is involved in host defence and
      inflammation by oxidation of numerous small molecules. This review summarises our
      current results on the determination of redox properties of all intermediates
      involved in the halogenation and peroxidase cycle of MPO. The standard reduction
      potentials of the redox couples compound I/native MPO, compound I/compound II of
      MPO, and compound II/native MPO have been determined to be 1.16 V, 1.35 V, and
      0.97 V, respectively, at pH 7 and 25 degrees C. Thus, for the first time, a full
      description of these important thermodynamic parameters of myeloperoxidase has
      been performed, allowing a better understanding of its extraordinary reactivity.

PMID- 14599341
TI  - The retina: oxidative stress and diabetes.
AB  - A prominent and early feature of the retinopathy of diabetes mellitus is a
      diffuse increase in vascular permeability. As the disease develops, the
      development of frank macular oedema may result in vision loss. That reactive
      oxygen species production is likely to be elevated in the retina, and that
      certain regions of the retina are enriched in substrates for lipid peroxidation,
      may create an environment susceptible to oxidative damage. This may be more so in
      the diabetic retina, where hyperglycaemia may lead to elevated oxidant production
      by a number of mechanisms, including the production of oxidants by vascular
      endothelium and leukocytes. There is substantial evidence from animal and
      clinical studies for both impaired antioxidant defences and increased oxidative
      damage in the retinae of diabetic subjects that have been, in the case of animal
      studies, reversible with antioxidant supplementation. Whether oxidative damage
      has a causative role in the pathology of diabetic retinopathy, and thus whether
      antioxidants can prevent or correct any retinal damage, has not been established,
      nor has the specific nature of any damaging species been characterised.

PMID- 14599342
TI  - Apomorphine attenuates 6-hydroxydopamine-induced apoptotic cell death in SH-SY5Y
      cells.
AB  - Enhanced oxidative stress is implicated in the pathogenesis of Parkinson's
      disease. The catecholaminergic neurotoxin 6-hydroxydopamine (6-OHDA) induces the
      production of reactive oxygen species (ROS), leading to neuronal cell death. On
      the other hand, apomorphine, a dopamine D1/D2 receptor agonist and known as a
      potent antioxidant, has been reported to have a neuroprotective effect. In the
      present study, we investigated the effect of apomorphine on 6-OHDA-induced
      apoptotic cell death using the human dopaminergic neuroblastoma cell line, SH
      SY5Y. The co-treatment of cells with apomorphine significantly attenuated 6-OHDA
      induced ROS generation, the phosphorylation of c-Jun N-terminal kinase (JNK), DNA
      fragmentation and subsequent apoptotic cell death. In addition, pretreatment with
      apomorphine for 24 h and the following concomitant treatment enhanced the
      protective effects against 6-OHDA-induced toxicity except for the attenuation of
      JNK phosphorylation. We also demonstrated that pretreatment alone with
      apomorphine for 24 h prior to the exposure confers resistance against 6-OHDA
      induced cell toxicity. These findings suggested that apomorphine acts principally
      as a radical scavenger to suppress the level of ROS and ROS-stimulated apoptotic
      signaling pathway, whereas the other mechanisms might be involved in the
      protective effects.

PMID- 14599343
TI  - Lack of protection of prior heat shock against UV-induced oxidative stress in
      human skin fibroblasts.
AB  - The effect of prior hyperthermia on UV-induced oxidative stress was studied in
      human skin fibroblasts. UV radiation alone induced an increased release of
      superoxide anions and increased lipid peroxidation in skin fibroblasts
      accompanied by a rise in catalase and superoxide dismutase activities.
      Hyperthermia was found to induce a significant rise in the cell content of heat
      shock proteins, HSP60 and HSP70, but this treatment prior to UV radiation did not
      influence any indicators of oxidative stress in the fibroblasts. In contrast, the
      combination of heat shock prior to UV-exposure reduced fibroblast cell viability
      compared with UV radiation-exposure alone.

PMID- 14599344
TI  - Antioxidant properties of the melatonin metabolite N1-acetyl-5-methoxykynuramine
      (AMK): scavenging of free radicals and prevention of protein destruction.
AB  - In numerous experimental systems, the neurohormone melatonin has been shown to
      protect against oxidative stress, an effect which appears to be the result of a
      combination of different actions. In this study, we have investigated the
      possible contribution to radical scavenging by substituted kynuramines formed
      from melatonin via pyrrole ring cleavage. N1-Acetyl-5-methoxykynuramine (AMK), a
      metabolite deriving from melatonin by mechanisms involving free radicals,
      exhibits potent antioxidant properties exceeding those of its direct precursor N1
      acetyl-N2-formyl-5-methoxykynuramine (AFMK) and its analog N1-acetylkynuramine
      (AK). Scavenging of hydroxyl radicals was demonstrated by competition with ABTS
      in a Fenton reaction system at pH 5 and by competition with DMSO in a hemin
      catalyzed H2O2 system at pH 8. Under catalysis by hemin, oxidation of AMK was
      accompanied by the emission of chemiluminescence. AMK was a potent reductant of
      ABTS cation radicals, but, in the absence of catalysts, a poor scavenger of
      superoxide anions. In accordance with the latter observation, AMK was fairly
      stable in a pH 8 H2O2 system devoid of hemin. Contrary to AFMK, AMK was easily
      oxidized in a reaction mixture generating carbonate radicals. In an oxidative
      protein destruction assay based on peroxyl radical formation, AMK proved to be
      highly protective. No prooxidant properties of AMK were detected in a sensitive
      biological test system based on light emission by the bioluminescent
      dinoflagellate Lingulodinium polyedrum. AMK may contribute to the antioxidant
      properties of the indolic precursor melatonin.

PMID- 14599346
TI  - Assessment of hydroxyl radical generation and radical scavenging activity of
      Chinese medicinal herbs using GC-MS.
AB  - Aqueous extracts of ten Chinese herbs were evaluated for their radical scavenging
      activity by a GC-MS method based on the Fenton reaction system. Hydroxylation of
      salicylate and phenylalanine is widely used as an index of hydroxyl radical
      formation in vivo and in vitro. A problem associated with quantifying product
      from such reactions is the generation of complex reaction products that increase
      background 'noise' and reduce sensitivity for the target product. The aim of this
      investigation was to develop a GC-MS methodology to assess in vitro hydroxyl
      radical production. In this method, hydroxyl radical was trapped by p
      hydroxyphenylacetic acid to form 3,4-dihydroxyphenylacetic acid (DOPAC) which was
      then selectively extracted from the reaction mixture using aluminium oxide and
      assayed by GC-MS. Selective adsorption and desorption of the catechol nucleus
      from aluminium oxide was shown to eliminate interference from non-catechol
      reaction products effectively. This system was applied to examine the hydroxyl
      radical scavenging activity of different herbal extracts. The results showed that
      the herb Dimocaepus Longan Lour exhibited the highest radical scavenging activity
      of all the herbs examined. With the use of a stable isotope-labelled internal
      standard, this system could be readily applied to in vitro methods which use 4
      hydroxybenzoic acid as a substrate for the hydroxyl radical.

PMID- 14599345
TI  - Protective effect of gossypitrin on carbon tetrachloride-induced in vivo
      hepatotoxicity.
AB  - Carbon tetrachloride (CCl4) is a known environmental biohazard, which induces
      lipid peroxidation (LPO) and oxidative damage in rat liver. In this study, the
      hepatoprotective effect of Gossypitrin, a flavonoid extracted from Hibiscus
      elatus S.W, was investigated against the CCl4-induced in vivo hepatotoxicity. The
      levels of malondialdehyde (MDA) were assayed as an index of LPO and the levels of
      catalase (CAT) activity as a biomarker of oxidative damage. Leakage of aspartate
      aminotransferase (ALT) and lactate dehydrogenase (LDH), liver weight/body weight
      ratio as well as morphological parameters were used as signs of hepatotoxicity.
      CCl4 (1 ml/kg), intraperitoneally injected into rats, caused increased MDA
      production and CAT activity, and also a significant ALT and LDH leakage as
      compared to levels of these constituents in the control group. Changes in
      morphology, including steatosis, cells forming balloon cells and necrosis were
      evaluated in the hepatotoxin-induced damage. Treatment of rats with Gossypitrin
      (3.98, 5.97 and 8.95 mg/kg) 2 h before and 2 h after CCl4 injection, protected
      hepatocytes against cell injury induced by CCl4 and its efficacy as an
      antioxidant was similar to vitamin E (used as a reference antioxidant). These
      results are consistent with the conclusion that the toxicity of CCl4 is due to
      LPO and the generation of reactive oxygen species (ROS), and that Gossypitrin's
      protective effects relate to its direct radical scavenging ability and other
      antioxidative processes induced by its structure.

PMID- 14599347
TI  - Population screening of single-nucleotide polymorphisms exemplified by analysis
      of 8000 alleles.
AB  - The authors describe a method in which the population frequency of single
      nucleotide polymorphisms (SNPs) can be efficiently detected and their allele
      frequencies accurately measured. Selected SNPs in TNFbeta, IL-4, and CTLA-4 were
      used to demonstrate the method. Blood from 4000 individuals was pooled, DNA was
      extracted, and target sequences were PCR amplified and analyzed by denaturant
      capillary electrophoresis. Alleles were separated into peaks based on melting
      properties of the double DNA helix. Frequencies of the different alleles were
      determined by calculating the area under the peaks. Allele frequencies and Hardy
      Weinberg equilibrium estimated from the pooled data were verified by analyzing
      7.5% of the samples randomly selected from the blood donor series. The method
      herein is equally suitable for single-samples and/or pooled-samples analysis of
      SNPs, in which sample treatment is kept to a minimum. The potential throughput of
      the method is beyond obtainable numbers of samples.

PMID- 14599348
TI  - A high-throughput, nonisotopic, competitive binding assay for kinases using
      nonselective inhibitor probes (ED-NSIP).
AB  - A novel competitive binding assay for protein kinase inhibitors has been
      developed for high-throughput screening (HTS). Unlike functional kinase assays,
      which are based on detection of substrate phosphorylation by the enzyme, this
      novel method directly measures the binding potency of compounds to the kinase ATP
      binding site through competition with a conjugated binding probe. The binding
      interaction is coupled to a signal amplification system based on complementation
      of beta-galactosidase enzyme fragments, a homogeneous, nonisotopic assay
      technology platform developed by DiscoveRx Corp. In the present study,
      staurosporine, a potent, nonselective kinase inhibitor, was chemically conjugated
      to a small fragment of beta-galactosidase (termed ED-SS). This was used as the
      binding probe to the kinase ATP binding pocket. The binding potencies of several
      inhibitors with diverse structures were assessed by displacement of ED-SS from
      the kinase. The assay format was specifically evaluated with GSK3alpha, an enzyme
      previously screened in a radioactive kinase assay (i.e., measurement of [(33)P]
      gamma-ATP incorporation into the kinase peptide substrate). Under optimized assay
      conditions, nonconjugated staurosporine inhibited ED-SS binding in a
      concentration-dependent manner with an apparent potency (IC(50)) of 11 nM, which
      was similar to the IC(50) value determined in a radioactive assay. Furthermore, 9
      kinase inhibitors with diverse structures, previously identified from chemical
      compound library screening, were screened using the competitive binding assay.
      The potencies in the binding assay were in very good agreement with those
      obtained previously in the isotopic functional activity assay. The binding assay
      was adapted for automated HTS using selected compound libraries in a 384-well
      microtiter plate format. The HTS assay was observed to be highly robust and
      reproducible (Z' factors > 0.7) with high interassay precision (R(2) > 0.96).
      Interference of compounds with the beta-galactosidase signal readout was
      negligible. In conclusion, the DiscoveRx competitive kinase binding assay, termed
      ED-NSIP trade mark, provides a novel method for screening kinase inhibitors. The
      format is homogeneous, robust, and amenable to automation. Because there is no
      requirement for substrate-specific antibodies, the assay is particularly
      applicable to Ser/Thr kinase assay, in which difficulties in identifying a
      suitable substrate and antibody preclude development of nonisotopic assays.
      Although the nonselective kinase inhibitor, staurosporine, was used here,
      chemically conjugating the ED fragment to other small molecule enzyme inhibitors
      is also feasible, suggesting that the format is generally applicable to other
      enzyme systems.

PMID- 14599349
TI  - A homogeneous enzyme fragment complementation cyclic AMP screen for GPCR
      agonists.
AB  - In the new high-throughput screening (HTS) campaign, receptor functional assays,
      3',5'-cyclic adenosine monophosphate (cAMP), intracellular [Ca(2)+](i),
      phosphatidylinositol turnover, and reporter-based assays are being used as
      primary screens as they are now developed as homogeneous and automation-friendly
      assays. FlashPlate assay and scintillation proximity assay using radiolabeled
      cAMP have been used for measuring cAMP. A nonradioactive homogeneous HTS assay
      using HitHunter trade mark enzyme fragment complementation (EFC) technology was
      evaluated for measuring cAMP in adherent and suspension cells overexpressing a
      Galpha(s)-coupled receptor. In the EFC-cAMP assay, the beta-galactosidase (beta
      gal) donor fragment-cAMP (ED-cAMP) conjugate complements with the beta-gal enzyme
      acceptor (EA) fragment to form an active beta-gal enzyme. Binding of ED-cAMP
      conjugate to the anti-cAMP antibody prevents its complementation with the EA
      fragment to form an active enzyme. Cyclic AMP in the samples compete with ED-cAMP
      to bind to the anti-cAMP antibody, thus increasing the free ED-cAMP that can
      complement with the EA fragment to form an active enzyme that is assayed with a
      luminescent substrate. Thus, this assay results in a positive signal unlike other
      technologies, wherein the signal is completed by cAMP in the sample. Glucagon
      like peptide (GLP)-1 binds to GLP-1 receptor (with a Kd of 0.2 nM) signals
      through Galpha(s) to activate adenylate cyclase, which results in an increase of
      intracellular cAMP (EC(50) of 0.3 nM). GLP-1 stimulation of cAMP levels measured
      by the EFC method was similar in both adherent and suspension cell formats
      (EC(50)~0.3 nM) at different cell numbers. The assay was further validated with
      forskolin, exendin, and several active GLP-1 peptide analogues. The stimulation
      of cAMP by GLP-1 and forskolin was effectively inhibited by the adenylate cyclase
      inhibitors MDL-12330A and SQ-22536, confirming that the increased cAMP is through
      the AC pathway. The assay tolerates dimethyl sulfoxide (DMSO) up to 10%, and
      tartrazine does not interfere with the assay with the adherent cells up to 1 mM
      and affects minimally up to 10 microM in suspension cells. The assay is very
      robust, with a Z' value of 0.7 to 0.8. The assay was validated with several
      plates of low molecular weight nonpeptide compounds and peptide agonists with
      different potencies. The suspension cell protocol is a robust homogeneous assay
      that involves fewer steps than the adherent cell protocol and is suitable for
      HTS. The cAMP assay using EFC technology is advantageous in that it has a greater
      dynamic range of detection; is nonradioactive, very sensitive, robust; has
      minimal interference from DMSO and colored compounds; and is amenable for
      automation. An added advantage of this assay is that the cAMP is measured as a
      positive signal, thereby reducing the incidence of false positives.

PMID- 14599350
TI  - High-throughput fluorescence polarization method for identification of FKBP12
      ligands.
AB  - FKBP12 is best known as the target of the widely used immunosuppressive drug
      FK506 but may also play a role in neuronal survival. Nonimmunosuppressive ligands
      of FKBP12 have been shown to have neuroprotective and neuroregenerative activity
      both in vitro and in vivo, stimulating interest in the development of high
      throughput screens to rapidly identify novel ligands. FKBP12 was expressed as a
      His(6)-fusion in bacteria and purified by metal ion affinity and gel filtration
      chromatography. A high-throughput fluorescence polarization assay was developed
      to identify novel ligands of FKBP12. Dissociation constant values of known FKBP12
      ligands measured by the new method agreed closely with K(i) values obtained by
      assaying inhibition of the rotamase activity of the enzyme. The fluorescence
      polarization assay is rapid, robust, and inexpensive and does not generate
      radioactive waste. It is very well suited for high-throughput screening efforts.

PMID- 14599352
TI  - Development of a high-throughput scintillation proximity assay for the
      identification of C-domain translational initiation factor 2 inhibitors.
AB  - Translational initiation factor 2 (IF2) is the largest of the 3 factors required
      for translation initiation in prokaryotes and has been shown to be essential in
      Escherichia coli. It stimulates the binding of fMet-tRNA(f)(Met) to the 30S
      ribosomal subunit in the presence of GTP. The selectivity is achieved through
      specific recognition of the tRNA(f)(Met) blocked alpha-amino group. IF2 is
      composed of 3 structural domains: N-domain, whose function is not known; G
      domain, which contains the GTP/GDP binding site and the GTPase catalytic center;
      and C-domain, which recognizes and binds fMet-tRNA(f)(Met). Its activity is
      strictly bacteria specific and highly conserved among prokaryotes. So far,
      antibiotics targeting IF2 function are not known, and this makes it an ideal
      target for new drugs with mechanisms of resistance not yet developed. A few
      assays have been developed in the past, which allow the detection of IF2 activity
      either directly or indirectly. In both instances, the assays are based on
      radioactive detection and do not allow for high throughput because of the need
      for separation or solvent extraction steps. The authors describe a novel
      biochemical assay for IF2 that exploits the molecular recognition of fMet
      tRNA(f)(Met) by the C-domain. The assay is based on the incubation of biotinyl
      IF2 with fMet-tRNA(f)(Met) and the subsequent capture of the radiolabeled complex
      by streptavidin-coated beads, exploiting the scintillation proximity assay (SPA)
      technology. The assay has been designed in an automatable, homogeneous,
      miniaturized fashion suitable for high-throughput screening and is rapid,
      sensitive, and robust to dimethyl sulfoxide (DMSO) up to 10% v/v. The assay, used
      to screen a limited chemical collection of about 5000 compounds and a subset of
      compounds originated by a 2-D substructural search, has shown to be able to
      detect potential IF2 inhibitors.

PMID- 14599351
TI  - Development of novel assays for proteolytic enzymes using rhodamine-based
      fluorogenic substrates.
AB  - Components within synthetic chemical and natural product extract libraries often
      interfere with fluorescence-based assays. Fluorescence interference can result
      when the intrinsic spectral properties of colored compounds overlap with the
      fluorescent probes. Typically, fluorescence-based protease assays use peptide
      amidomethylcoumarin derivatives as substrates. However, because many organic
      compounds absorb in the ultraviolet region, they can interfere with coumarin
      based fluorescence assays. Red-shifted fluorescent dyes such as peptidyl
      rhodamine derivatives are useful because there is generally less interference
      from organic compounds outside the ultraviolet wavelengths. In this report,
      rhodamine-based fluorogenic substrates, such as bis-(Leu)(2)-Rhod110 and bis-(Ala
      Pro)-Rhod110, were developed for leucine aminopeptidase and dipeptidyl
      aminopeptidase. Novel, tandem rhodamine substrates such as Ala-Pro-Rhod110-Leu
      were designed with 2 protease cleavage sites and used to assay 2 proteases in a
      multiplex format. General endpoint high-throughput screening (HTS) assays were
      also developed for leucine aminopeptidase, dipeptidyl aminopeptidase, and trypsin
      that incorporated both amidomethylcoumarin and rhodamine-based fluorogenic
      substrates into a single screening format. These dual-substrate assays allowed
      for the successful screening of the LOPAC trade mark collection and natural
      product extracts despite high levels of fluorescence interference.

PMID- 14599354
TI  - A standard operating procedure for assessing liquid handler performance in high
      throughput screening.
AB  - The thrust of early drug discovery in recent years has been toward the
      configuration of homogeneous miniaturized assays. This has allowed organizations
      to contain costs in the face of exponential increases in the number of screening
      assays that need to be run to remain competitive. Miniaturization brings with it
      an increasing dependence on instrumentation, which over the past several years
      has seen the development of nanodispensing capability and sophisticated detection
      strategies. To maintain confidence in the data generated from miniaturized
      assays, it is critical to ensure that both compounds and reagents have been
      delivered as expected to the target wells. The authors have developed a standard
      operating procedure for liquid-handling quality control that has enabled them to
      evaluate performance on 2 levels. The first level provides for routine daily
      testing on existing instrumentation, and the second allows for more rigorous
      testing of new dispensing technologies. The procedure has shown itself to be
      useful in identifying both method programming and instrumentation performance
      shortcomings and has provided a means to harmonizing instrumentation usage by
      assay development and screening groups. The goal is that this type of procedure
      be used for facilitating the exchange of liquid handler performance data across
      the industry.

PMID- 14599353
TI  - Colorimetric assays for biodegradation of polycyclic aromatic hydrocarbons by
      fungal laccases.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are highly toxic organic pollutants
      widely distributed in terrestrial and aquatic environments. In the present work,
      2 colorimetric assays for laccase-catalyzed degradation of PAHs were developed
      based on studies of the oxidation of 12 aromatic hydrocarbons by fungal laccases
      from Trametes versicolor and Myceliophthora thermophila. Using a sodium
      borohydride water-soluble solution, the authors could reduce the single product
      of laccase-catalyzed anthracene biooxidation into the orange-colored 9,10
      anthrahydroquinone, which is quantifiable spectrophotometrically. An assay using
      polymeric dye (Poly R-478) as a surrogate substrate for lignin degradation by
      laccase in the presence of mediator is also presented. The decolorization of Poly
      R-478 was correlated to the oxidation of PAHs mediated by laccases. This
      demonstrates that a ligninolytic indicator such as Poly R-478 can be used to
      screen for PAH-degrading laccases; it will also be useful in screening mutant
      libraries in directed evolution experiments. Poly R-478 is stable and readily
      soluble. It has a high extinction coefficient and low toxicity toward white rot
      fungi, yeast, and bacteria, which allow its application in a solid-phase assay
      format.

PMID- 14599357
TI  - Development of a 1-microl scale assay for mitogen-activated kinase kinase 7 using
      2-D fluorescence intensity distribution analysis anisotropy.
AB  - This paper describes the development of a robust, miniaturizable, and
      quantitative fluorescence-based assay for mitogen-activated protein kinase kinase
      7 (MKK7). As a first step, the basic steady-state kinetics of the MKK7-catalyzed
      phosphorylation of c-Jun N-terminal kinases (JNKs) 1, 2, and 3 were defined using
      standard radiometric methods. Subsequently, the authors found that in addition to
      the holo JNKs, a series of novel small peptides (based on the region around the
      JNK phosphorylation site) are also substrates, provided that these were
      prephosphorylated on the Y residue of the TPY motif. One of these peptide
      substrates was used in the development of a fluorescence polarization-based assay
      using an antibody as a sensor. The assay was successfully miniaturized for use
      with conventional fluorescence polarization (FP) reader technology in 8.5 microl
      and on the single microl scale using Evotec proprietary 2-dimensional
      fluorescence intensity distribution analysis (2D-FIDA) anisotropy and liquid
      handling technology. The steady-state kinetic parameters derived using the FP or
      2D-FIDA anisotropy format assays correlated well with those generated using a
      radiometric assay. Moreover, the quantitative sensitivity to known inhibitors was
      maintained independent of the format and assay volume. In addition, the authors
      found that the 2D-FIDA anisotropy assay exhibited superior performance statistics
      (typical Z' = approximately 0.5) relative to conventional FP (typical Z' = 0.3)
      and yielded the additional benefit of order-of-magnitude savings in terms of
      reagent costs. The 2D-FIDA anisotropy assay was used to carry out a successful
      high-throughput screening in 1-microl final volume against company file
      compounds.

PMID- 14599358
TI  - A strategy for high-throughput assay development using leads derived from nuclear
      magnetic resonance-based screening.
AB  - A strategy is described for the development of high-throughput screening assays
      against targets of unknown function that involves the use of nuclear magnetic
      resonance (NMR) spectroscopy. Using this approach, molecules that bind to the
      protein target are identified from an NMR-based screen of a library of
      substrates, cofactors, and other compounds that are known to bind to many
      proteins and enzymes. Once a ligand has been discovered, a fluorescent or
      radiolabeled analog of the ligand is synthesized that can be used in a high
      throughput screen. The approach is illustrated in the development of a high
      throughput screening assay against HI-0033, a conserved protein from Haemophilus
      influenzae whose function is currently unknown. Adenosine was found to bind to HI
      0033 by NMR, and fluorescent analogs were rapidly identified that bound to HI
      0033 in the submicromolar range. Using these fluorescent compounds, a
      fluorescence polarization assay was developed that is suitable for high
      throughput screening and obtaining detailed structure-activity relationships for
      lead optimization.

PMID- 14599359
TI  - Phage display of functional human TNF-alpha converting enzyme catalytic domain: a
      rapid method for the production of stabilized proteolytic proteins for assay
      development and high-throughput screening.
AB  - The catalytic domain of human tumor necrosis factor-alpha (TNF-alpha) converting
      enzyme (TACE) was expressed in a phage display system to determine whether stable
      and active enzyme could be made for high-throughput screening (HTS). This would
      address many issues around screening of proteases in this class. The phage
      displayed TACE catalytic domain (PDT) properly cleaved the fusion protein of
      glutathione S-transferase (GST)-pro-TNF-alpha to generate the mature TNF-alpha in
      vitro. To determine the utility of the PDT in HTS, the authors further
      demonstrated that PDT was able to generate a strong reproducible fluorescence
      signal by cleaving a fluorogenic TNF-alpha-specific peptide in vitro. More
      important, the catalytic activity of the PDT was inhibited by a broad-spectrum
      matrix metalloprotease (MMP) inhibitor but not by an MMP-I specific inhibitor,
      illustrating the potential utility of PDT for HTS. The PDT was also compared with
      baculovirus-expressed TACE (BET) in these assays to establish the relative
      efficacy of PDT. Both PDT and BET showed a similar specific cleavage profile
      against the defined substrates. Activity of the BET, however, was stable at 4
      degrees C for less than 24 h. In contrast, the PDT exhibited remarkable
      stability, losing very little activity even after 2 years at 4 degrees C. On the
      basis of these results, the authors concluded that the phage display system might
      be a useful tool for expressing proteins that have stability issues related to
      auto-proteolytic activity. Furthermore, the ease and low cost of large-scale
      production of phage should make it suitable for assay development and HTS.

PMID- 14599360
TI  - A versatile high-throughput screen for inhibitors of lipid kinase activity:
      development of an immobilized phospholipid plate assay for phosphoinositide 3
      kinase gamma.
AB  - The family of phosphoinositide 3-kinases (PI3K) regulates fundamental cellular
      responses such as proliferation, apoptosis, motility, and adhesion. In
      particular, the PI3K gamma isoform plays a critical role in the control of cell
      migration. Despite the attractiveness of PI3-kinases as drug targets, drug
      discovery efforts have been hampered by the lack of appropriate lipid kinase
      assay formats suitable for high-throughput screening. The authors report the
      development of a simple and robust 384-well plate assay that is based on(33) P
      phosphate transfer from radiolabeled [gamma(33) P]ATP to phosphatidylinositol
      immobilized on Maxisorp plates. The established assay format for PI3K gamma was
      easily adapted to the automated screening platform and was successfully employed
      for high-throughput screening. Enzymatic and inhibition characteristics of
      recombinant human PI3K gamma determined with the plate assay are in very good
      agreement with previously reported values determined in other assay formats.
      Maximal catalytic activity of PI3K gamma was observed at pH 7.0. The apparent
      K(m) value for ATP using a 1:1 mixture of phosphatidylinositol and
      phosphatidylserine was determined to be 7.3 microM (6.0-8.6 microM, 95%
      confidence interval [CI]). IC(50) values for known PI3-kinase inhibitors were
      determined to be 1.45 nM (1.17-1.80 nM, 95% CI) for wortmannin and estimated from
      partial inhibition data to be 1400, 2830, and 21,400 nM for quercetin, LY294002,
      and staurosporine, respectively. This novel assay approach allows for screening
      of inhibitors of lipid kinases in high-throughput mode and thereby may facilitate
      the identification of novel inhibitory structures for drug development.

PMID- 14599361
TI  - Cell-based high-throughput screening assay system for monitoring G protein
      coupled receptor activation using beta-galactosidase enzyme complementation
      technology.
AB  - A novel cell-based functional assay to directly monitor G protein-coupled
      receptor (GPCR) activation in a high-throughput format, based on a common GPCR
      regulation mechanism, the interaction between beta-arrestin and ligand-activated
      GPCR, is described. A protein-protein interaction technology, the InteraX trade
      mark system, uses a pair of inactive beta-galactosidase (beta-gal) deletion
      mutants as fusion partners to the protein targets of interest. To monitor GPCR
      activation, stable cell lines expressing both GPCR- and beta-arrestin-beta-gal
      fusion proteins are generated. Following ligand stimulation, beta-arrestin binds
      to the activated GPCR, and this interaction drives functional complementation of
      the beta-gal mutant fragments. GPCR activation is measured directly by
      quantitating restored beta-gal activity. The authors have validated this assay
      system with two functionally divergent GPCRs: the beta2-adrenergic amine receptor
      and the CXCR2 chemokine-binding receptor. Both receptors are activated or blocked
      with known agonists and antagonists in a dose-dependent manner. The beta2
      adrenergic receptor cell line was screened with the LOPAC trade mark compound
      library to identify both agonists and antagonists, validating this system for
      high-throughput screening performance in a 96-well microplate format. Hit
      specificity was confirmed by quantitating the level of cAMP. This assay system
      has also been performed in a high-density (384-well) microplate format. This
      system provides a specific, sensitive, and robust methodology for studying and
      screening GPCR-mediated signaling pathways.

PMID- 14599362
TI  - High-throughput screening for ion channel modulators.
AB  - Ion channels present a group of targets for major clinical indications, which
      have been difficult to address due to the lack of suitable rapid but biologically
      significant methodologies. To address the need for increased throughput in
      primary screening, the authors have set up a Beckman/Sagian core system to fully
      automate functional fluorescence-based assays that measure ion channel function.
      They apply voltage-sensitive fluorescent probes, and the activity of channels is
      monitored using Aurora's Voltage/Ion Probe Reader (VIPR). The system provides a
      platform for fully automated high-throughput screening as well as pharmacological
      characterization of ion channel modulators. The application of voltage-sensitive
      fluorescence dyes coupled with fluorescence resonance energy transfer is the
      basis of robust assays, which can be adapted to the study of a variety of ion
      channels to screen for both inhibitors and activators of voltage-gated and other
      ion channels.

PMID- 14599363
TI  - Use of a fluorescent imaging plate reader--based calcium assay to assess
      pharmacological differences between the human and rat vanilloid receptor.
AB  - The cloned vanilloid receptor 1 (VR1) is a ligand-gated calcium channel that is
      believed to be the capsaicin-activated vanilloid receptor found in native
      tissues, based on similarities regarding molecular mass, tissue distribution, and
      electrophysiological properties. Using a Fluorescent Imaging Plate Reader
      (FLIPR), along with Fluo-3 to signal intracellular calcium levels ([Ca(++)](i)),
      rat VR1 (rVR1) and a human orthologue (hVR1) were pharmacologically characterized
      with various VR1 ligands. HEK-293 cells, stably expressing rVR1 or hVR1,
      exhibited dose-dependent increases in [Ca(++)](i) when challenged with capsaicin
      (EC(50)s congruent with 10 nM). Responses to capsaicin were blocked by the VR1
      antagonist capsazepine and were dependent on VR1 expression. Potencies for 10
      structurally diverse VR1 agonists revealed rVR1 potencies highly correlated to
      that of hVR1 (R(2) = 0.973). However, a subset of agonists (tinyatoxin, gingerol,
      and zingerone) was approximately 10-fold more potent for rVR1 compared to hVR1.
      Schild analysis for blockade of capsaicin-induced responses by capsazepine was
      consistent with competitive antagonism, whereas ruthenium red displayed
      noncompetitive antagonism. Compared to rVR1, hVR1 was more sensitive to blockade
      by both antagonists. For both rVR1 and hVR1, time-response waveforms elicited by
      resiniferatoxin increased more gradually compared to other agonists. Tinyatoxin
      also displayed slow responses with hVR1 but showed rapid responses with rVR1.
      Thus, FLIPR technology can be used to readily reveal differences between rVR1 and
      hVR1 pharmacology with respect to potencies, efficacies, and kinetics for several
      VR1 ligands.

PMID- 14599367
TI  - Which cytology results predict cervical intraepithelial neoplasia?

PMID- 14599366
TI  - Reinventing practice: technology that works?

PMID- 14599368
TI  - Extended-release oxybuytynin and tolterodine treat overactive bladder.

PMID- 14599369
TI  - Carvedilol superior to metoprolol for preventing death from CHF.

PMID- 14599370
TI  - Does finasteride prevent prostate cancer?

PMID- 14599371
TI  - Impermeable bed covers ineffective for asthma.

PMID- 14599372
TI  - Local heat decreases renal colic pain.

PMID- 14599373
TI  - Heparin prevents recurrent VTE in cancer patients.

PMID- 14599374
TI  - Routine induction reduces cesarean rate.

PMID- 14599375
TI  - Nebulized epinephrine does not help bronchiolitis.
AB  - Nebulized epinephrine does not improve clinical status or reduce the length of
      the hospital stay in infants aged <1 year with acute bronchiolitis. It also does
      not reduce clinical scores during or shortly after medication administration. In
      this study, infants requiring oxygen and intravenous fluids-presumably the
      sickest infants in the study-required longer hospital stays if they received
      epinephrine. A wheezing infant may be presenting with a first episode of asthma,
      so a trial of bronchodilators would seem reasonable; however, it appears that the
      primary intervention for bronchiolitis is supportive treatment, with supplemental
      oxygen, intravenous fluids, and ventilatory support when needed.

PMID- 14599376
TI  - Red clover extracts not effective for hot flushes.
AB  - Both red clover extracts and placebo equally reduce the frequency of hot flushes.
      Providers should encourage patients to avoid spending money on supplements and
      instead add soy to their diet. In general, however, if patients are already
      convinced that something works, don't discourage them.

PMID- 14599377
TI  - Clear choices in managing epidermal tinea infections.

PMID- 14599378
TI  - New rash on the right hand and neck.

PMID- 14599379
TI  - Number needed to treat.

PMID- 14599380
TI  - Enhanced vs unenhanced cardia stress imaging.

PMID- 14599381
TI  - Can I find a doctor? Availability of primary care physicians in the San Francisco
      Bay Area.
AB  - OBJECTIVES: Primary care physicians function as "gatekeepers" in many managed
      care systems. With the rapid growth of managed care enrollment, it is crucial
      that patients have adequate access to primary care physicians. We investigated
      factors associated with new-patient appointment availability of primary care
      physicians in the San Francisco Bay Area. STUDY DESIGN: Observational cohort.
      POPULATION: Cross-sectional survey of primary care physician offices in 2 San
      Francisco Bay Area counties (n=438). OUTCOMES MEASURED: New-patient appointment
      availability. RESULTS: Seventy-five percent of primary care physicians
      participating in managed care had an appointment available for a new patient.
      Appointments were more likely to be available with primary care physicians who
      had been in practice for 10 years or less (odds ratio [OR]=4.2; 95% confidence
      interval [CI], 1.7-10.3), compared with more established physicians; and with
      primary care physicians who had graduated from a medical school outside of the
      United States (OR=3.5; 95% CI, 1.7-7.3), compared with US graduates. Appointments
      within 30 days were less available with female primary care physicians (OR=0.4;
      95% CI, 0.2-0.7) than for male primary care physicians. CONCLUSIONS: The limited
      availability of appointments for new patients may create barriers to primary care
      in the San Francisco Bay Area, a region with high managed-care penetration.

PMID- 14599382
TI  - Prevention and treatment of influenza.

PMID- 14599383
TI  - Clinical inquiries. Does stimulant therapy help adult ADHD?

PMID- 14599384
TI  - Clinical inquiries. Does a high-fiber diet prevent colon cancer in at-risk
      patients?

PMID- 14599385
TI  - Clinical inquiries. Is screening urinalysis in children worthwhile?

PMID- 14599386
TI  - Clinical inquiries. Should jaundiced infants be breastfed?

PMID- 14599387
TI  - Clinical inquiries. What is the best initial treatment of Parkinson's disease?

PMID- 14599389
TI  - [Poor trends in cardiac arrest mortality in Spain].

PMID- 14599390
TI  - [Effect of the availability of a medicalized mobile ICU (MMICU) on the hospital
      admissions after an out-of-hospital cardiorespiratory arrest (OH-CRA)].
AB  - Patients admitted in an ICU after OH-CRA before and after the implementation of a
      MMICU were evaluated. During a period of 11 years, divided into a pre-MMICU
      period (1988-1993) and a post-MMICU period (1994-1998), 39 patients were admitted
      in the pre period and 64 patients in the post period. The basal characteristics,
      the etiologies of OH-CRA and of death in ICU they were similar. The incidence of
      severe anoxic encephalopathy (SAE) it doubled in the post period. There were not
      significant differences both to the discharge from ICU and to the hospital
      discharge. We conclude that after implementing a MMICU more patients are admitted
      in ICU resuscitated after OH-CRA. The survival does not vary, but the incidence
      of SAE increases.

PMID- 14599391
TI  - [Usefulness of a new fast technique for detection of pneumococcal antigen in the
      diagnosis of community pneumonia].
AB  - With the objective of analyzing the usefulness of a new technique of fast
      detection of pneumococcal antigen in urine (Binax NOW Streptococcus pneumoniae
      urinary antigen test) 163 community pneumonia episodes were reviewed. The test
      was positive in 30 cases, and gave rise to therapeutic implications in 12
      patients. The global sensitivity was 57%, being superior in patients with HIV
      infection (70%), and the specificity was 91.6%. In 16 episodes it was the only
      diagnostic test of pneumococcal infection. The determination of pneumococcal
      antigen through this technique is a useful tool for the diagnosis of community
      pneumonia, mainly due its high specificity.

PMID- 14599392
TI  - [Microalbuminuria and clinical proteinuria as the main predictive factors of
      cardiovascular morbidity and mortality in patients with type 2 diabetes].
AB  - CONTEXT: [corrected] The principal objective was that of evaluating the
      independent contribution of microalbuminuria and clinical proteinuria to the
      cardiovascular morbidity and mortality in patients with type 2 diabetes. METHODS:
      A prospective cohort study with selection of patients with type 2 diabetes
      evaluated in hospital outpatient consultations. Through the Cox proportional
      risks model the predictive importance of the presence of microalbuminuria and
      clinical proteinuria on the appearance of fatal and non-fatal cardiovascular
      complications (angina, fatal and non-fatal myocardial infarction, sudden death,
      transitory ischemic attack, fatal and non-fatal stroke, or amputation of lower
      limbs) was analyzed. RESULTS: The monitoring of 463 patients was done during an
      average period of 4.64 years (SD: 1.56). There were 330 patients (71.3%) with
      normoalbuminuria, 106 (22.9%) with microalbuminuria and 27 (5.8%) with
      proteinuria. The global cardiovascular morbidity and mortality rate was 3.7%
      annual (2.46% annual for the patients with normoalbuminuria, 5.6% for the
      patients with microalbuminuria and 14.42% for the patients with proteinuria; p <
      0.0001). After multiple adjustment, both microalbuminuria (RR: 1.91; 95% CI: 1.05
      3.48; p = 0.032) and proteinuria (RR: 4.15; 95% CI: 1.77-9.75; p = 0.0011) were
      the main independent predictive factores of appearance of cardiovascular
      complications. Other predictive variables were age (RR: 1.06; 95% CI: 1.02-1.10;
      p = 0.0014), HDL cholesterol (RR = 0.96; 95% CI: 0.93-0.98; p = 0.001), LDL
      cholesterol (RR: 1.01; 95% CI: 1.002-1.02; p = 0.016) and initial presence of
      ischemic cardiopathy (RR: 1.97; 95% CI: 1.03-3.76; p = 0.041). CONCLUSIONS: The
      increase in the rate of excretion of urinary albumin is the main independent
      predictive factor of cardiovascular morbidity and mortality in patiens with type
      2 diabetes.

PMID- 14599393
TI  - [High resolution computerized tomography in pulmonary tuberculosis with negative
      sputum bacilloscopy].
AB  - CONTEXT: Pulmonary tuberculosis with negative sputum bacilloscopy involves
      diagnostic difficulties when there are not available liquid culture media due to
      the slow growth of Mycobacterium tuberculosis in the traditional culture media,
      and also due to the need for carrying out invasive examinations. OBJECTIVE:
      Evaluate the high resolution computerized tomography findings (HRCT) in patients
      with pulmonary tuberculosis and negative bacilloscopy of sputum. METHOD:
      Prospectively 28 patients (12 with active tuberculosis and 16 with inactive
      tuberculosis) were evaluated through HRCT, assessing the following findings:
      centrolobular nodules, multiple branched linear structures, macronodules,
      cavitation, consolidation, enlargement of interlobular septums, ground-glass
      change, bronchiectases, emphysema, broncovascular distortion, fibrotic changes,
      calcified mediastinal adenopathies, parenchymous calcification, pleural
      enlargement, and pleural effusion. RESULTS: The findings that were associated
      significantly to the active disease were: consolidation (67%), macronodules (67%)
      and centrolobular nodules (67%). The presence of centrolobular nodules and/or
      consolidation had a sensitivity of 83% and a specificity of 87%. The findings
      significantly associated to inactive disease were bronchiectases (87%) and
      broncovascular distortion (62%). CONCLUSION: Our results support the value of
      HRCT in patients with pulmonary tuberculosis and negative sputum bacilloscopy,
      since the finding of centrolobular nodules and/or consolidation has good
      sensitivity and specificity for the diagnosis of active pulmonary disease.

PMID- 14599394
TI  - [Ofujis papuloerythroderma. Presentation of 3 cases and review of its concept and
      etiology].
AB  - Ofuji's papuloerythroderma is not a specific clinical entity, but a concequence
      of numerous inflammatory dermatoses and neoplasms. Some authors advocate that it
      is possible to find this erupcion in elderly patients with different types of
      erythroderma of known or unknown origin. It is necessary to recognize this
      condition since these patients can develop a lymphoma in the future. In this
      article three atopic patients are described with clinical lesions of
      papuloerythroderma respecting the cutaneous folds, with eosinophilia, increase of
      the IgE levels and histological characteristics of atopic eczema. We think that
      atopic dermatitis should be considered in the etiologic study of patients with
      papuloerythroderma.

PMID- 14599395
TI  - [Troponinosis in the emergency services].

PMID- 14599396
TI  - [Early detection of colon cancer. Individual and collective strategies].

PMID- 14599397
TI  - [A triptan for every patient?].

PMID- 14599398
TI  - [Intravenous immunoglobulins in the systemic autoinmune diseases].

PMID- 14599399
TI  - [Prolonged fever and right costal pain in patient with a history of brucellosis].

PMID- 14599400
TI  - [Indurated red violet mass of fast growth in abdominal left flank].

PMID- 14599401
TI  - [Lung mass in a 80-year-old women with epistaxis and anemia].

PMID- 14599402
TI  - [Empirical treatment of eosinophilias. Prevent the complications of
      strongyloidiasis].

PMID- 14599403
TI  - [Pulmonary tromboembolism. Another risk of travelling].

PMID- 14599404
TI  - [Splenic abscess by Streptococcus bovis. First case in Spain and literature
      review].

PMID- 14599406
TI  - [Comparison of population coronary heart disease risk estimated by the Framingham
      original and REGICOR calibrated functions].
AB  - BACKGROUND AND OBJECTIVE: The therapeutic consequences of using the Framingham
      function calibrated by the REGICOR and Framingham investigators (Framingham
      REGICOR) in the Spanish population are unknown. The objective of this study was
      to determine the differences in the classification of the population coronary
      risk when using the classical Framingham function (Framingham-Wilson) and that
      calibrated, and its consequences on the theoretical indication of lipid-lowering
      treatment. PATIENTS AND METHOD: The classification into the < 2%, 2-4,9%, 5-9,9%,
      10-19,9%, 20-39,9%, and >= 40% risk categories observed by the two functions was
      compared in 3.270 individuals aged 35 to 74 years with no history of ischaemic
      heart disease or lipid-lowering drug treatment, recruited in two population
      samples representative of Girona between 1994 and 2001. The number of lipid
      lowering treatment candidates was estimated applying the most recent guidelines
      for clinical practice, according to the risk level obtained with both functions.
      RESULTS: The proportion of patients excluded owing to the fact that they already
      were on lipid-lowering treatment was 6.2%. The Framingham-REGICOR assigned 54.2%
      of women and 67.9% of men to a lower level of risk as compared to the Framingham
      Wilson function. In 0.2% of women and 21.2% of men the decrease was two
      categories of risk. The figures in diabetic participants were 75.7 and 18.5%,
      respectively. When the European recommendations published in 2003 were applied,
      lipid-lowering treatment would have been indicated in 14.5% and in 4.4% of non
      diabetic participants by the Framingham-Wilson and the Framingham-REGICOR,
      respectively. CONCLUSIONS: The calibrated Framingham-REGICOR function assigns a
      lower coronary risk category in more than 50% of women and almost 90% of men than
      the uncalibrated Framingham function. The calibrated function is more suitable
      for risk estimation in primary prevention than the original function in Spain.

PMID- 14599407
TI  - [Clinical use of statins and cholesterol goals in patients with several
      cardiovascular risk factors].
AB  - BACKGROUND AND OBJECTIVE: Our goal was to determine the number of patients who
      achieve low-density lipoprotein cholesterol (LDL-c) targets according to new
      guidelines. PATIENTS AND METHOD: Descriptive and transversal study of patients
      from a cardiovascular clinic. LDL-c was calculated and targets were established
      according the NCEP-ATP III. RESULTS: 1,811 patients (46% males, 54% females) were
      studied. 35% of these were high-risk patients (group 1: coronary risk > 20% at 10
      years), 19% were intermediate-risk patients (group 2: coronary risk 10-20% at 10
      years) and 46% were low-risk patients (group 3: coronary risk < 10% at 10 years).
      Overall, 58% of patients achieved target LDL-c levels, yet success rates were 26%
      among group 1 patients, 51% among group 2 patients, and 86% among group 3
      patients (p = 0.001, for differences between groups). Statin treatment was
      significantly related to achieving target LDL-c levels in group 1 patients (OR =
      1.7; 95% CI, 1.2-2.4; p = 0.007). In group 1.41% of patients had LDL-c levels >
      130 mg/dl without receiving lipid-lowering drugs. CONCLUSIONS: Although an
      overall 58% patients achieve target LDL-C levels, only one of four high-risk
      patients have LDL-c levels < 100 mg/dl, and statin treatment is a determining
      factor to achieve this goal. These findings indicate that a more aggressive
      treatment with statins is needed in secondary prevention.

PMID- 14599408
TI  - [A randomized clinical trial to compare the effectiveness of indinavir, ritonavir
      and saquinavir].
AB  - BACKGROUND AND OBJECTIVE: HIV protease inhibitors (PI) were licensed without a
      direct evidence of their relative efficacy. PATIENTS AND METHOD: 137 patients
      attending our clinics between November 1997 and March 1998, to whom treatment
      with a PI was recommended, were randomized to receive indinavir (IDV), saquinavir
      (SQV) or ritonavir (RTV). Main outcome variables were one-year mean changes in
      HIV-RNA plasma concentrations and CD4 cells counts and proportion of patients
      with HIV viral load below level of detection. RESULTS: Mean HIV viral load
      reductions were 0.95 for SQV, 0.72 for IDV and 0.65 for RTV (p = 0.44), equaling
      losses and changes to failures. In a standard intent-to-treat analysis, mean
      changes in viral load were 1.16, 1.01 and 1.50 (p = 0.21), respectively. The
      proportion of patients with undetectable viral load was 50%, with no differences
      between treatment arms. CONCLUSIONS: No differences were observed in the
      effectiveness of SQV, IDV and RTV.

PMID- 14599409
TI  - [Can genes predict the response to treatment with statins?].

PMID- 14599410
TI  - [Paraoxonase, something more than an enzyme?].
AB  - Coronary heart disease is one of the major causes of death in developed
      countries. The hypothesis that peroxidation of low density lipoproteins (LDL) may
      be the initial step of the atherosclerotic process has promoted numerous studies
      aimed at investigating the mechanisms by which the body protects itself from such
      oxidative phenomena. Among these mechanisms we find the paraoxanase (PON) enzyme,
      which is quite thriving the last decades. This enzyme is principally associated
      with high density lipoproteins (HDL) but it also seems to help LDL to recover
      their antioxidant status. This paper reviews different aspects concerning the
      mechanisms implicated in the induction and activity of this enzyme, as well as
      its production, attachment to HDL, and modifications of its activity due to
      external factors. The use of genetic techniques, the study of the polimorphisms
      of the PON enzyme and the possibility of increasing paraoxonase activity by means
      of pharmacotherapy and/or dietary therapy open new perspectives with regard to
      coronary heart disease treatment and prevention.

PMID- 14599411
TI  - [Prevention and control of imported tuberculosis].

PMID- 14599412
TI  - [Arrhythmogenic right ventricular dysplasia in an old woman: arrhythmic storm as
      initial presentation].

PMID- 14599413
TI  - [Arrhythmogenic right ventricular dysplasia in a young woman with recurrent
      syncope].

PMID- 14599414
TI  - [An unusual case of tricuspid endocarditis by Enterococcus faecalis in native
      valve].

PMID- 14599415
TI  - [Eating disorders in Spain: are we ready to take public health action?].

PMID- 14599416
TI  - [Economic evaluation papers in Gaceta Sanitaria: some reflections].

PMID- 14599417
TI  - [Analysis of the mechanisms of minor occupational injuries in the construction
      industry in Spain].
AB  - OBJECTIVES: The construction industry produces the highest number of occupational
      injuries in Spain (25.6%). Of these, 98.5% were minor injuries with 5 million
      workdays lost in 2000. This occurred even after the recent introduction of
      numerous health and occupational safety regulations. The objective of the present
      study was to identify the specific mechanisms of minor occupational injuries in
      the construction sector. METHODS: In 2000, there were 235,853 minor occupational
      injuries in the construction industry. From these, injuries in general
      construction and civil engineering were selected (n = 155,044). These injuries
      affected both the total number of workers in the sector as well as bricklayers
      and unskilled construction workers. Insurance and financial activities (n =
      2,019) were selected as a reference economic sector. Minor occupational injuries
      due to nontraumatic processes (heart attack, etc.) were taken as a control group
      (n = 167), assuming that the risk of nontraumatic processes was independent of
      economic activities. Odds ratios (OR) were adjusted by age, sex, years of work
      experience, type of employment and company size through nonconditional logistic
      regression models. RESULTS: The mechanisms with the highest risk of minor
      occupational lesions in construction workers as a group compared with employees
      in the financial sector were projection of fragments (OR = 33.0; 95% CI, 15.3
      70.8) and being struck by objects (OR = 18.2; CI 95%, 9.7-34.1). These were also
      the most specific mechanisms of injury in the subgroup of bricklayers and
      unskilled construction workers. CONCLUSIONS: Activities aimed at preventing minor
      occupational injuries in the construction sector should be orientated towards
      these mechanisms, especially projection of fragments despite the low frequency of
      this mechanism compared with that of other mechanisms. Case-control design is a
      useful alternative approach for research into occupational injuries.

PMID- 14599418
TI  - [Factors associated with hospitalization for ambulatory care sensitive conditions
      in municipalities].
AB  - OBJECTIVES: To describe variability in admission rates for ambulatory care
      sensitive conditions (ASSC) in municipalities in the catchment area of a tertiary
      hospital and to determine the influence of primary care characteristics,
      socioeconomic factors, health of the population, and geographical accessibility
      to the hospital on this variability. METHODS: An ecological study was carried out
      in 34 municipalities in the area served by the Hospital Virgen de las Nieves in
      Granada (Spain) including all admissions for ASSC from 1997 to 1999. The
      admission rates for men and women were calculated separately and were age
      standardized by the indirect method. The following factors were analyzed as
      independent variables: characteristics of primary care (type of healthcare model
      and type of center), socioeconomic factors (unemployment rate, income per capita,
      number of business establishments, size of municipality), health (mortality
      rate), and accessibility (time in minutes from the municipality to the hospital).
      A multiple lineal regression model was estimated. RESULTS: A total of 9.8% of all
      hospital admissions were due to ASSC. The mean annual admission rate was 10
      admissions per 1.000 inhabitants. This rate was higher for men and for persons
      aged more than 74 years. The standardized admission ratios were not statistically
      different from 1 in 56% of the municipalities and were higher than 1 in 26% and
      lower than 1 in 18%. Sixty-two percent of the variability in rates for men was
      associated with time taken to reach the hospital, size of municipality, the
      interaction between both variables, and mortality. Eighteen percent of the
      variability in rates for women was associated with time taken to reach the
      hospital and the unemployment rate. CONCLUSIONS: Variability in admission rates
      for ASSC was not associated with primary care characteristics in the geographical
      area analyzed. Accessibility (measured as time to the hospital) was the only
      variable associated with higher rates in both men and women. Admission rates for
      ASSC among women were higher when unemployment rates were higher, and rates among
      men were higher in larger municipalities and in those with higher mortality.

PMID- 14599419
TI  - [Identification of variables influencing waiting times for specialized care].
AB  - OBJECTIVE: To identify the variables influencing waiting time for specialized
      care (waiting lists) through multiple regression analysis and to analyze the
      health districts with long waiting times according to these variables. DESIGN:
      Descriptive, cross sectional and retrospective study of waiting times for access
      to specialized care between 1997 and 1998. SETTING: Area 20 of the Health
      Department of the Autonomous Community of Valencia (Spain) consisting of 12
      health districts with 204,424 inhabitants. INTERVENTIONS: The following variables
      were gathered: variables influencing demand: type of municipality, aging and
      indexes of dependent population, and percentage of pensioners; variables
      influencing supply: age, sex, training and professional stability of the doctor,
      and size of the patient list; variables influencing resource consumption:
      percentage of referrals to specialized care per thousand inhabitants, mean WT for
      access to specialized care (in natural days) by district and year, number of
      consultations, and workload. A multiple regression model was constructed through
      (backward) elimination, taking the mean WT as the dependent variable and the
      remaining variables as independent variables. The resulting equation enabled
      calculation of the expected WT per health district and the deviation of the real
      WT from the expected WT. A district was considered to have a high WT when its
      deviation was above the mean plus one standard deviation of the distribution.
      RESULTS: The mean WT for access to specialized care was 37 days in 1997 and 34
      days in 1998. A significant correlation (p < 0.005) was found between WT and the
      percentage of the population aged less than 14 years (r = 0.693), the percentage
      of the population aged between 14-65 years (r = 0.517), the number of
      consultations (r = 0.689), and coastal population (r = 0.470). Our final model
      included: percentage of the population aged less than 14 years, number of
      consultations, and coastal population (F = 41.803; p < 0.000; r = 0.945; r2 =
      0.893). Three districts (37.5%) with high WTs were identified. CONCLUSIONS: The
      number of consultations, the percentage of the pediatric population, and
      proximity to the coast were closely correlated with WT for specialized care, with
      a consequent influence on waiting lists.

PMID- 14599420
TI  - [Comparison of two models of prescription quality indicators in primary care].
AB  - OBJECTIVES: To assess the quality of prescriptions in primary care area through
      indicators established by a team of physicians and to analyze the relationship
      between these indicators and those used by the Spanish public health system
      (INSALUD) in the same area. METHODS: An observational, cross sectional study was
      performed in a primary care area in Asturias with 156,614 inhabitants and 9
      health centers. An overall quality score was obtained for each of the physicians
      in the primary care area by using quality indicators and standards agreed on by
      the prescribers themselves. The relationship between the score obtained and the
      indicators normally used in the area by INSALUD and pharmaceutical cost was also
      analyzed. RESULTS: Mean compliance with the optimal standard was 29%. The mean
      overall quality score was 3.24. None of the physicians achieved the maximum score
      of 11. No significant association was found between the score and the indicators
      for drugs of limited clinical value. Adherence to the pharmaceutical guide for
      the area was positively correlated with quality (r = 0.44, p < 0.001). A negative
      linear association (p < 0.001) was found between the overall quality score and
      incurred cost. The adjusted coefficient of determination was 0.29. CONCLUSIONS:
      Poor prescribing quality was widespread. Indicators for drugs of limited clinical
      value, frequently used as a measure of quality, showed no relationship with
      quality. Adherence to the area's pharmaceutical guide remains a valid indicator
      of prescribing quality. Overall, there was a correlation between higher quality
      and lower prescribing cost, although this correlation was not found for
      individual physicians.

PMID- 14599421
TI  - [National survey of preoperative management and patient selection in ambulatory
      surgery centers].
AB  - BACKGROUND: The objective of this study was to determine both the selection and
      preparation criteria in patients in various Spanish ambulatory surgery centers,
      as well as the impact of these criteria on their results. The results were
      compared according to the type of functional structure of the units (autonomous
      or integrated). MATERIAL AND METHODS: We performed a cross sectional, descriptive
      study through postal survey. The survey contained the following items: type of
      unit, surgical procedures, selection criteria, preoperative assessment and
      management, and qualitative and quantitative indexes of the activity performed in
      2000. A total of 123 units were included with a response rate of 39%. RESULTS:
      The selection criteria showed a high degree of consensus. The outpatient
      anesthesia clinic was used for preoperative assessment by 97.9% of the units.
      Most units routinely requested preoperative tests (hemostasis and hemogram by
      89%; biochemical parameters by 72.9%) and to a lesser extent chest X-ray (33.3%)
      and electrocardiogram (35.4%). The introduction of procedures for the management
      of coexisting diseases was scarce (25-64.6%). Units using the outpatient
      anesthesia clinic in all patients had a lower cancellation rate (1.5% vs 4.4%).
      Autonomous units were significantly more likely to accept patients with high
      surgical-anesthetic risk than integrated units. Autonomous units also showed a
      significantly lower number of admissions (1.2% vs 1.9%, p = 0.003), mean stay
      (240 min vs 367 min, p = 0.002), and recovery time (150 min vs 212 min, p =
      0.001) than integrated units. No statistically significant differences were found
      in the remaining parameters. CONCLUSIONS: Scientifically based protocols for
      patient selection, preoperative assessment and perioperative management of
      distinct processes and for the rational use of laboratory tests should be more
      widely used. The need for an outpatient anesthesia clinic for preoperative
      assessment was notable. The results of our survey indicate that better results in
      performance indexes are achieved in autonomous ambulatory surgery units than in
      integrated units. Given the possibility of defining and validating quality
      standards, further multicenter studies should be performed.

PMID- 14599422
TI  - [Economic evaluation of pharmacotherapies for smoking cessation].
AB  - INTRODUCTION: Public policies for smoking cessation are mainly based on advice
      from the primary care physician and group therapy. Several pharmacological
      treatments to reduce tobacco addiction are currently available. One of these
      treatments, bupropion, has remarkable efficacy (30% over 1 year) compared with
      nicotine replacement therapies (chewing gum 8%, patches 17% over 1 year). The
      objective of this study was to assess the efficiency of three smoking cessation
      strategies based on pharmacotherapies in Spain. MATERIAL AND METHODS: The current
      situation of methods for smoking cessation in Spain includes a mixture of primary
      care physician advice, group therapy and willpower, combined with the use of
      drugs in a small proportion of individuals. This situation was compared with
      three scenarios in which the use of the available pharmacotherapies was increased
      (by up to 10%) for 1 year. A cost-effectiveness evaluation was used to calculate
      the cost per death prevented and per year of life saved in each scenario. The
      analysis used a time horizon of 20 years and was based on an adaptation of the
      HECOS model, sponsored by WHO-Euro, which enables comparison of distinct
      pharmacotherapy interventions. Epidemiological data were based on the National
      Health Survey (1997) and the National Institute of Statistics (1999). RESULTS:
      The cost-effectiveness ratio of bupropion at 5 years was 70,939 euros per death
      prevented and was 37,305 euros per year of life saved. When the time horizon was
      increased to 20 years, these figures became net savings of 28,166 and 3,265
      euros, respectively. The cost-effectiveness ratios for both nicotine gums and
      patches were higher than that for bupropion: 171,834 euros per death prevented at
      5 years and 90,362 euros per year of life saved for patches and 513,004 euros per
      death prevented and 269,772 euros per year of life saved at 5 years. Furthermore,
      bupropion treatment for 1 year would prevent a greater number of deaths than the
      alternative strategies (approximately 3,000 deaths in a time horizon of 20 years)
      due to the decrease in the number of smokers. CONCLUSIONS: The cost of some
      tobacco cessation methods, such as primary care physician advice and group
      therapy, is low but their efficacy is also low. New drug treatments increase
      costs and also achieve higher efficacy rates. When assessing interventions and
      their costs economic evaluation shows that in the long run greater use of
      bupropion generates net savings in tobacco-related health costs.

PMID- 14599423
TI  - [Increase in differences in survival according to income per capita in Spain in
      the last quarter of the twentieth century].
AB  - OBJECTIVE: To estimate probability of survival in Spain from 1975 to 1995
      according to income per capita quintiles. METHODS: The 50 provinces in Spain were
      ordered by income per capita in 1975, 1981, 1985, 1990 and 1995. For each
      quintile and year we estimated the probability of surviving 75 years from birth
      and the probability of survival in several age intervals in men and women.
      Probability was estimated by percentages. Subsequently, we calculated differences
      in the probability of survival between the highest and the lowest income per
      capita quintiles. RESULTS: Differences in the probability of surviving from birth
      to the age of 75 years increased from 1.3 in 1975 to 3.1 in 1995 in women,
      whereas in men the increase was from 0.1 in 1975 to 3.7 in 1995. CONCLUSIONS: In
      Spain, as in other developed countries, socioeconomic differences in premature
      mortality increased in the latter decades of the twentieth century.

PMID- 14599425
TI  - [Factors conditioning primary care services utilization. Empirical evidence and
      methodological inconsistencies].
AB  - INTRODUCTION: In Spain, the degree and characteristics of primary care services
      utilization have been the subject of analysis since at least the 1980s. One of
      the main reasons for this interest is to assess the extent to which utilization
      matches primary care needs. In fact, the provision of an adequate health service
      for those who most need it is a generally accepted priority. FACTORS CONDITIONING
      USE: The evidence shows that individual characteristics, mainly health status,
      are the factors most closely related to primary care utilization. Other personal
      characteristics, such as gender and age, could act as modulators of health care
      need. Some family and/or cultural variables, as well as factors related to the
      health care professional and institutions, could explain some of the observed
      variability in primary care services utilization. Socioeconomic variables, such
      as income, reveal a paradox. From an aggregate perspective, income is the main
      determinant of utilization as well as of health care expenditure. When data are
      analyzed for individuals, however, income is not related to primary health
      utilization. METHODOLOGICAL INCONSISTENCIES: The situation is controversial, with
      methodological implications and, above all, consequences for the assessment of
      the efficiency in primary care utilization. Review of the literature reveals
      certain methodological inconsistencies that could at least partly explain the
      disparity of the empirical results. Among others, the following flaws can be
      highlighted: design problems, measurement errors, misspecification, and
      misleading statistical methods.Some solutions, among others, are quasi
      experiments, the use of large administrative databases and of primary data
      sources (design problems); differentiation between types of utilization and
      between units of analysis other than consultations, and correction of measurement
      errors in the explanatory variables (measurement errors); consideration of
      relevant explanatory variables (misspecification); and the use of multilevel
      models (statistical methods).

PMID- 14599424
TI  - [Prevalence of urinary incontinence in the population aged more than 64 years in
      Galicia, Spain].
AB  - OBJECTIVE: To determine the prevalence of urinary incontinence in the Galician
      population aged more than 64 years. METHODS: We performed a descriptive study,
      based on a personal interview with each individual from a sample of the target
      population. The sample was obtained through random sampling stratified into
      urban, semi-urban and rural of the Autonomous Community of Galicia. Subsequently,
      a random sample was extracted from the database of the individual health cards of
      selected localities. A total of 350 interviews in 12 sampling locations were
      performed. RESULTS: The prevalence of urinary incontinence in Galicia in 2002 was
      35.14% (95% CI: 31-38%, 15-28 for men and 38-51% for women). CONCLUSIONS: One out
      of three Galicians aged more than 64 years presents urinary incontinence. The
      prevalence is almost double in women.

PMID- 14599427
TI  - [Experimental, innovative and standard procedures. Ethics and science in the
      introduction of medical technology].
AB  - The dividing lines between experimental, innovative and standard medical
      procedures are frequently blurred in current clinical practice. This is even more
      true in the fields of surgery and implantable devices. These differ substantially
      from pharmacological interventions, which are better regulated.However, the
      character of the various medical interventions applied in human subjects should
      be ethically and scientifically delimited as clearly as possible. This task
      cannot be abandoned to personal discretion and criteria, which are currently
      used, especially in the field of surgical innovation. External and independent
      review of the risk-benefit ratio of proposed innovations should enable
      specification of the particular features of a technique in the patient-doctor
      relationship, as well as the ethical and scientific requirements for more
      appropriate evaluation.

PMID- 14599428
TI  - [Clinical management in an angiology and vascular surgery unit. Results of the
      application of a clinical practice protocols].
AB  - OBJECTIVES: The aim of this study was to analyze the impact of clinical
      management on quality indicators in a vascular surgery unit over a 10-year
      period. METHODS: We performed a retrospective analysis of quality indicators from
      1990 to 2001 and of the influence of a clinical practice protocol and standards
      of quality on these indicators. RESULTS: Comparison of both periods revealed
      improvement in all the quality indicators. The safety of surgical procedures was
      unaffected by the application of management protocols and clinical pathways.
      CONCLUSIONS: Clinical management based on the cost-quality binomial can ensure
      the efficiency of a hospital unit without adversely affecting quality of care.
      Quality standards based on hospital resource use, morbidity and mortality can be
      defined for groups of procedures.

PMID- 14599429
TI  - [Mortality due to alcohol consumption in Castilla-La Mancha [Spain], 1980-1998].

PMID- 14599430
TI  - [Pleasure and health].

PMID- 14599431
TI  - Analysis of neurological disease in four dimensions: insight from ALS-PDC
      epidemiology and animal models.
AB  - The causal factor(s) responsible for sporadic neurological diseases are unknown
      and the stages of disease progression remain undefined and poorly understood. We
      have developed an animal model of amyotrophic lateral sclerosis-parkinsonism
      dementia complex which mimics all the essential features of the disease with the
      initial neurological insult arising from neurotoxins contained in washed cycad
      seeds. Animals fed washed cycad develop deficits in motor, cognitive, and sensory
      behaviors that correlate with the loss of neurons in specific regions of the
      central nervous system. The ability to recreate the disease by exposure to cycad
      allows us to extend the model in multiple dimensions by analyzing behavioral,
      cellular, and biochemical changes over time. In addition, the ability to induce
      toxin-based neurodegeneration allows us to probe the interactions between genetic
      and epigenetic factors. Our results show that the impact of both genetic causal
      and susceptibility factors with the cycad neurotoxins are complex. The article
      describes the features of the model and suggests ways that our understanding of
      cycad-induced neurodegeneration can be used to decipher and identify the early
      events in various human neurological diseases.

PMID- 14599432
TI  - Liability to substance use disorders: 1. Common mechanisms and manifestations.
AB  - Variation in the risk for and severity of substance use disorders (SUD) in the
      population is caused by multiple organismic (genetic, biochemical, psychological)
      and environmental factors. Whereas drug- or drug-class-specific liability
      mechanisms exist, a substantial proportion of variance in the risk is shared
      between specific liabilities, reflecting mechanisms that determine common
      liability to SUD. Data from epidemiologic, clinical, psychological,
      physiological, biochemical, and family and genetic studies reviewed in this paper
      indicate the existence of mechanisms and characteristics shared in common by
      liabilities to SUD related to different drugs. These mechanisms can be
      conceptualized as common liability to SUD, a latent trait accounting for a
      substantial portion of variation in SUD risk and severity and determined by all
      factors influencing the probability of SUD development. An accompanying paper
      describes an approach to the quantitative estimation of this trait.

PMID- 14599433
TI  - Liability to substance use disorders: 2. A measurement approach.
AB  - Liabilities to complex disorders, discussed in the accompanying paper, present
      difficulties in measurement related to the arbitrariness of diagnostic threshold
      definitions and problems with discrimination between trait values, especially
      within the 'normal' individuals. The inability to quantitatively estimate the
      risk for a disorder, such as substance use disorders (SUD), is an obstacle for
      studying etiological (e.g. genetic) mechanisms and developing efficient
      prevention and treatment measures. Based on the concept of common liability to
      SUD, this paper delineates an application of the longitudinal family/high-risk
      design and item response theory to the development of a continuous index of
      liability. The method has been tested in both simulation study and empirical
      data. The approach described affords the opportunity to quantitatively estimate
      the risk for SUD at an early age and before any drug exposure. This method is
      also applicable to measuring liabilities to other complex disorders, especially
      those with relatively late onset.

PMID- 14599434
TI  - The interpretation of the measurement of nucleus accumbens dopamine by in vivo
      dialysis: the kick, the craving or the cognition?
AB  - Psychopharmacological studies have implicated the dopaminergic innervation of the
      nucleus accumbens (NAC) in reward and reinforcement, in the actions of addictive
      drugs, and in the control of the symptoms of schizophrenia. Recent developments
      in in vivo dialysis, and other in vivo neurochemical techniques have permitted a
      more direct analysis of the behavioural correlates of increased dopamine release
      in rats, and have largely confirmed these findings in relation to reward, and
      drugs of abuse potential. However, dopamine release has also been found to be
      increased by many other stimuli/situations including aversive stimuli, stimuli
      conditioned to aversive stimuli, complex novel stimuli, and in the process of
      conditioning itself. These results contrast with electrophysiological data
      obtained in the behaving monkey, where rewarding stimuli, or stimuli predictive
      of reward are associated with increased firing of presumptive dopamine neurones
      projecting to the NAC (and indeed to the striatum), but mild aversive stimuli are
      not, leading to the suggestion that this system subserves a more purely reward
      function, or indeed that it provides a reward error signal. Further exploration
      of these issues will depend upon a comparison of increased dopamine cell firing
      and increased dopamine release, and an analysis of the behavioural effects of
      blocking these increases in dopamine transmission. One suggestion, deriving from
      work on latent inhibition, is that the significance of dopamine release by
      salient stimuli is to allow learning about stimuli which would otherwise be
      excluded on the basis of familiarity. This suggests that in addition to a role in
      some types of learning about salient stimuli, dopamine release in NAC may have a
      role in controlling the attention paid to familiar stimuli. Since it is difficult
      to see a connection between simple learning about rewards, and the symptoms of
      schizophrenia, this provides a more convincing link between the dopamine theory
      of schizophrenia, and the attentional difficulties held by many theorists to
      underlie schizophrenic symptoms.

PMID- 14599435
TI  - Amygdalar control of the mesocorticolimbic dopamine system: parallel pathways to
      motivated behavior.
AB  - The present review focuses on recent findings from our laboratory showing that
      there are major differences in the influence exerted by the central (CeN) and
      basolateral (BLA) nuclei of the amygdala on dopamine (DA) efflux in the nucleus
      accumbens (NAc) of the rat. Based on these data, we propose that the CeN
      maintains control, via an indirect pathway, of the tonic activity of a population
      of ventral tegmental dopamine neurons that specifically regulate basal DA efflux
      in the NAc. Related experiments also support the hypothesis that control of
      mesocorticolimbic DA activity by the CeN can influence the incentive value of the
      sensory property of food and its modulation by the drive-state of the animal. In
      contrast, we suggest that activation of the BLA can evoke transient increases in
      DA efflux in the NAc and medial prefrontal cortex (mPFC) and may also stabilize
      the activity of dopaminergic neurons projecting to the mPFC. We hypothesize that
      the rapid transient regulation of DA efflux in the NAc by the BLA plays an
      essential role in the selection and co-ordination of specific sequences of
      behaviors appropriate to incentive stimuli present in the environment. In this
      manner, the amygdala may exert differential control on motivated behavior,
      thereby ensuring the selection of behavioral responses that are optimal for
      survival.

PMID- 14599436
TI  - The medial prefrontal cortex in the rat: evidence for a dorso-ventral distinction
      based upon functional and anatomical characteristics.
AB  - The prefrontal cortex in rats can be distinguished anatomically from other
      frontal cortical areas both in terms of cytoarchitectonic characteristics and
      neural connectivity, and it can be further subdivided into subterritories on the
      basis of such criteria. Functionally, the prefrontal cortex of rats has been
      implicated in working memory, attention, response initiation and management of
      autonomic control and emotion. In humans, dysfunction of prefrontal cortical
      areas with which the medial prefrontal cortex of the rat is most likely
      comparable is related to psychopathology including schizophrenia, sociopathy,
      obsessive-compulsive disorder, depression, and drug abuse. Recent literature
      points to the relevance of conducting a functional analysis of prefrontal
      subregions and supports the idea that the area of the medial prefrontal cortex in
      rats is characterized by its own functional heterogeneity, which may be related
      to neuroanatomical and neurochemical dissociations. The present review covers
      recent findings with the intent of correlating these distinct functional
      differences in the dorso-ventral axis of the rat medial prefrontal cortex with
      anatomical and neurochemical patterns.

PMID- 14599438
TI  - Drugs of abuse and abuse of drugs in sportsmen: the role of in vitro models to
      study effects and mechanisms.
AB  - A particular field of analytical chemistry applied to forensic toxicology is
      represented by the anti-doping analysis, where biological samples (urine and in
      some instances blood) collected, either "in competition" or "out of competition",
      from athletes ruled for national/international sport federations, are analyzed to
      detect the putative use of prohibited substances and methods. Together with the
      official anti-doping activity to test the athletes (i.e. who engages in
      competitive sport) for the non-physiological enhancement of sport performance, it
      is mandatory to activate a new strategy of doping control, that should
      necessarily comprise a deep and exhaustive toxicological evaluation of the entire
      spectrum of doping substances and methods. An outline of the present status and
      of the future trends of the antidoping research is here presented, showing that
      most of the new tasks could greatly benefit from an approach based on in vitro
      methods, ranging from specific toxicity studies to the possible detection of new
      forms of doping.

PMID- 14599439
TI  - Endocrine disruptors: effects on male fertility and screening tools for their
      assessment.
AB  - During the recent decades, a lot of research has been performed concerning the so
      called "endocrine disruptors", which are widespread in the environment. These
      compounds of anthropogenic or natural origin mimic the action of sex hormones and
      can interfere with the endocrine system. The largest body of evidence exists for
      those compounds that are estrogenic in nature, but the amount of experimental
      data on other types of interactions, especially anti-androgenic, steadily
      increases. Because of the growing public and scientific concern, epidemiological
      studies have been initiated to analyse the short and long-term effects of
      endocrine disruptors. In addition, a number of assays have been developed and are
      undergoing validation, aiming at high throughput screening of chemical agents
      with suspected endocrine disrupting properties. In the present review, we briefly
      describe the results of epidemiological studies dealing with observed time trends
      in male fertility disorders. In the second part of the article, an overview is
      given of the different classes of endocrine disruptors, followed by a description
      of the most important in vitro and in vivo bioassays, used to screen for the
      possible endocrine disruptive capacity of chemicals, together with future
      research needs for in vitro test development.

PMID- 14599440
TI  - Ecotoxicological evaluation of carbamazepine using six different model systems
      with eighteen endpoints.
AB  - The occurrence of pharmaceutically active compounds in the aquatic environment
      has been recognized as one of the emerging issues in environmental chemistry.
      However, the ecotoxicological effects of pharmaceuticals have still not been
      researched adequately. Carbamazepine, an anticonvulsant commonly present in
      surface and groundwater, was studied, using six ecotoxicological model systems
      with eighteen endpoints evaluated at different exposure time periods. The battery
      included the immobilization of Daphnia magna, bioluminescence inhibition in the
      bacterium Vibrio fischeri, growth inhibition of the alga Chlorella vulgaris, and
      micronuclei induction and root growth inhibition in the plant Allium cepa. Cell
      morphology, neutral red uptake, total protein content, MTS metabolization,
      lactate dehydrogenase leakage and activity and glucose-6-phosphate dehydrogenase
      activity were studied in the salmonid fish cell line RTG-2. The total protein
      content, LDH activity, neutral red uptake and MTT metabolization in Vero monkey
      kidney cells were also investigated. The most sensitive system to carbamazepine
      was the Vero cell line, followed by Chlorella vulgaris, Vibrio fischeri, Daphnia
      magna, Allium cepa, and RTG-2 cells. EC50 values from 19 microM in Vero cells at
      72 h to more than 1200 microM in other systems, were obtained. Comparing the
      concentrations in water and the toxicity quantified in our assay systems,
      carbamazepine is not expected to produce acute toxic effects in the aquatic biota
      under these circumstances, but chronic and synergistic effects with other
      chemicals cannot be excluded.

PMID- 14599441
TI  - Effects of the metals on dihydropteridine reductase activity.
AB  - Metals are the oldest toxins known to human. Particularly, occupational and
      environmental exposure to aluminium, lead, mercury, cadmium, and manganese cause
      serious health problems by interaction with biological systems. Cellular targets
      of these metals are mostly specific biochemical processes (enzymes) and/or
      membranes of cells and organelles. To prevent and/or reduce the untoward or
      irreversible toxic effects of the metals by using biomarkers are as important as
      to know and to understand of their toxicity mechanisms. Dihydropteridine
      reductase (DHPR), which possessed essential thiol groups at the activity site,
      plays a crucial role in the maintenance of tetrahydrobiopterin (BH4). BH4 is the
      cofactor in the synthesis and regulation of neurotransmitters. A limited number
      of the evidences have shown that DHPR may be a target for the metals. Therefore,
      the present study was designed to assess possible in vitro effects of the
      commonly exposed metals on the enzyme activity. It was found that aluminium,
      cadmium, mercury, di-phenyl mercury, lead, diethyl lead, in chloride forms, and
      manganese, in sulphate form, led to statistically significant decreases in DHPR
      activity, in a concentration-dependent manner, in vitro.

PMID- 14599442
TI  - Comparative effects of cadmium, copper, paraquat and benzo[a]pyrene on the actin
      cytoskeleton and production of reactive oxygen species (ROS) in mussel
      haemocytes.
AB  - The immune defence of mussels is comprised of cell-mediated and humoral
      mechanisms, in which haemocytes or blood cells play a key role. Environmental
      pollutants such as metallic and organic xenobiotics exert immunotoxical effects
      on aquatic organisms. Some of these xenobiotics are known to give rise to highly
      reactive oxygen species (ROS), thereby leading to oxidative damage to tissue
      macromolecules including DNA, proteins and lipids. Previously we have detected
      enhancement of ROS production together with severe alterations in the actin
      cytoskeleton after exposure of mussel haemocytes to the carcinogenic polycyclic
      aromatic hydrocarbon benzo[a]pyrene (b[a]p). In a similar way, cadmium is also
      known to cause disruption of the actin cytoskeleton in mussel haemocytes, however
      it is not known whether this effect occurs by direct action or through ROS
      production. The aim of the present study was to decipher whether cytoskeletal
      alterations caused by Cd in mussel haemocytes are linked to increased ROS
      production. ROS-producing model compounds copper (Cu), paraquat and b[a]p were
      used in parallel experiments for comparative purposes. In all contaminant
      exposure experiments actin cytoskeleton appeared damaged. On the other hand, ROS
      production was increased in paraquat and b[a]p exposure experiments but decreased
      in haemocytes exposed to Cu while no significant effects were detected in Cd
      exposure experiments. In conclusion, it appears that deleterious effects of Cu
      and Cd on the integrity of the actin cytoskeleton of haemocytes are not directly
      linked to ROS production, at least at the exposure conditions used in the present
      study.

PMID- 14599443
TI  - Effects of the new-identified amphibole fluoro-edenite in lung epithelial cells.
AB  - An epidemiological survey on mortality for malignant pleural neoplasm in Italy
      evidenced a number of patients in Biancavilla, a village located in a volcanic
      area of eastern Sicily, none of which had been significantly exposed to asbestos
      during their professional lives. Environmental studies suggested the involvement
      of the material derived from stone quarries in the disease onset. A detailed
      crystal-chemical analysis of amphiboles contained in this material allowed the
      discovery and the identification of a new fiber that was named fluoro-edenite. In
      order to define the mode of action of fluoro-edenite at a subcellular level, we
      have conducted a study by using A549 cells, a tumor-cell line from a human lung
      carcinoma with properties of alveolar epithelial cells. The results obtained
      showed a remarkable tropism of A549 cells toward fluoro-edenite fibers. In fact,
      these epithelial cells contacted the fibers via the extension of membrane ruffles
      and filopodia that allowed the capture and most probably the internalization of
      material into the cytoplasm. Moreover, fluoro-edenite interfered with epithelial
      cell physiology, by reducing the proliferation rate without perturbing the cell
      cycle and increasing the release of the proinflammatory cytokine IL-6, one of the
      main mediators of asbestos-induced pathophysiological response.

PMID- 14599445
TI  - Overexpression of HSP70 is induced by ionizing radiation in C3H 10T1/2 cells and
      protects from DNA damage.
AB  - Various kinds of stress such as heat, UV, gamma-rays and chemicals that cause DNA
      damage induce heat shock proteins (Hsps), and in particular Hsp70. The Hsps
      cytoprotective function is not fully understood, although these proteins act as
      molecular chaperones or modulators of intracellular levels of reactive oxygen
      species (ROS). Recently, Hsps have been proposed to play a significant role in
      DNA repair after UV or gamma-ray irradiation. Ionizing radiation targets DNA
      molecules either via direct interaction or via production of free radicals and
      ROS. When exposed to gamma-rays C3H 10T1/2 cells are radiosensitive, therefore we
      decided to use them to investigate Hsp induction after ionizing radiation and
      their protective role against DNA damage. Here we demonstrate the induction of
      Hsps by gamma-rays, and investigate the kinetics of expression after irradiation
      at different doses. We also show that Hsp70 overexpression acts as a
      radioprotective mechanism towards the first event of DNA damage and increases
      long term viability. A preliminary investigation on the cell cycle does not
      evidence a significant protective action of inducible Hsp70 on it.

PMID- 14599444
TI  - Different induction of metallothioneins and Hsp70 and presence of the membrane
      transporter ZnT-1 in HepG2 cells exposed to copper and zinc.
AB  - Eukaryotic cells respond to stressful environmental stimuli, such as toxic
      concentrations of heavy metals, by rapidly synthesising defence proteins: the
      metallothioneins (MT) and the heat shock protein 70 (Hsp70). In this study we
      have analysed how the human hepatoblastoma cell line HepG2 responds to exposure
      to excess copper (30 microg/ml) and zinc (50 microg/ml) for long exposure times
      (48 and 72 h). Accumulation of the two metals, as measured by ICP-AES, was time
      dependent reaching a plateau after 72 h. HepG2 cells responded by dramatically
      increasing levels of MT during stress, mostly during zinc exposure. A time lag in
      Hsp70 induction was observed as the levels of this protein increased only after
      removal of the stress from culture medium (recovery) for 24 h, thus suggesting
      that the two defence mechanisms are not coordinated in a metal-induced stress
      response. Moreover in HepG2 cells, immunochemical and fluorescence techniques
      showed the presence and the localisation of the zinc membrane exporter ZnT-1 as a
      further mechanism of defence/homeostasis against zinc toxicity.

PMID- 14599446
TI  - Biological effects of atmospheric particles on human bronchial epithelial cells.
      Comparison with diesel exhaust particles.
AB  - Epidemiological studies have associated the increase of respiratory disorders
      with high levels of ambient particulate matter (PM) levels although the
      underlying biological mechanisms are unclear. PM are a complex mixture of
      particles with different origins but in urban areas, they mainly contain soots
      from transport like Diesel exhaust particles (DEP). In order to determine whether
      PM biological effects can be explained by the presence of DEP, the effects of
      urban PM, DEP and carbon black particles (CB) were compared on a human bronchial
      epithelial cell line (16-HBE14o-). Two types of PM were used : reference material
      (RPM) and PM with an aerodynamic diameter < or =2.5 microm collected in Paris
      with a high volume sampler (VPM). From 10 to 30 microg/cm2, cell viability was
      never modified whatever the particles. However, DEP and to a lower extent PM
      inhibited cell proliferation, induced the release of a pro-inflammatory cytokine,
      GM-CSF, and generated a pro-oxidant state as shown by the increased intracellular
      peroxides production. By contrast, CB never induced such effects. Nevertheless CB
      are more endocytosed than DEP whereas PM are the less endocytosed particles. In
      conclusion, PM induced to a lower extent the same biological effects than DEP in
      16-HBE cells suggesting that particle characteristics should be thoroughly
      considered in order to clearly correlate adverse effects of PM to their
      composition and to clarify the role of DEP in PM effects.

PMID- 14599447
TI  - The toxicity of H2O2 on the ionic homeostasis of airway epithelial cells in
      vitro.
AB  - Oxygen species may be formed in the air spaces of the respiratory tract in
      response to environmental pollution such as particulate matter. The mechanisms
      and target molecules of these oxidants are still mainly unknown but may involve
      modifications of the ionic homeostasis in epithelial cells. Cytosolic
      concentrations of Ca2+ (Fura2) and Na+ (SBFI) and short-circuit current (Isc)
      were followed in primary cultures of human nasal epithelial cells and in the cell
      line 16HBE14o- after exposure to H2O2 or *OH (H2O2 + Fe2+). Cells were grown on
      glass coverslips for ionic imaging or on permeable snapwell inserts for Isc
      studies. Exposure of the apical as well as the basal side of the cultures to H2O2
      or *OH induced a concentration-dependent transient increase in Isc which is due
      to a transient secretion of Cl-. Cai also increased transiently with
      approximately the same kinetics. The response was dependent on the release of
      calcium from intracellular stores. Nai on the contrary increased steadily over
      more than an hour. When the apical membrane was permeabilized with gramicidin,
      *OH inhibited the Na+ current (a measure of Na(+)-K(+)-ATPase activity in the
      baso-lateral membrane). The arrest of the pump was significant after 30 min
      exposure to oxidant. On the other hand no increase in the apical or baso-lateral
      sodium conductances could be detected. The progressive arrest of the Na+/K(+)
      pump may contribute to the sustained elevation of Nai. This strong modification
      in the cellular ionic homeostasis may participate in the stress response of the
      respiratory epithelium through alterations in signal transduction pathways.

PMID- 14599448
TI  - Micronucleus induction in cells co-exposed in vitro to 50 Hz magnetic field and
      benzene, 1,4-benzenediol (hydroquinone) or 1,2,4-benzenetriol.
AB  - The generation, transmission (e.g. power lines, transformers, service wires, and
      electrical panels), and use (e.g. home appliances, such as electric blankets,
      shavers, and televisions) of electrical energy is associated with the production
      of weak electric and magnetic fields (EMF) which oscillate 50 (Europe) or 60
      (USA) times per second (power-line frequency), falling in the extremely-low
      frequency (ELF) region of the electromagnetic spectrum. Epidemiological reports
      suggest a possible association between exposure to ELF-EMF and an increased risk
      of cancer (e.g. childhood acute leukaemia). Benzene is an established human
      leukomogen. This xenobiotic, which is unlikely to be the ultimate carcinogen, is
      metabolized in the liver to its primary metabolite phenol, which is hydroxylated
      to hydroquinone (1,4-benzenediol) and 1,2,4-benzenetriol. In this in vitro
      approach, to test the genotoxic and / or co-genotoxic potency of ELF-EMF, the
      cytokinesis block micronucleus (MN) method with Jurkat cells has been used. A 50
      Hz magnetic field (MF) of 5 mT field strength was applied for different length of
      time (from 1 to 24 h), either alone or with benzene, 1,4-benzenediol, or 1,2,4
      benzenetriol. Our preliminary results show that, after 24 h exposure, the
      frequency of micronucleated cells in MF-exposed cultures is 1.9 fold higher than
      in sham-exposed (control) cultures. Benzene exposure does not show any
      cytogenetic activity, whereas 1,4-benzenediol or 1,2,4-benzenetriol alone
      significantly affect the number of MN in Jurkat cells, as compared to untreated
      cultures. Moreover, co-exposure to ELF-MF does not seem to affect the frequency
      of micronuclei induced by benzene, 1,4-benzenediol, or 1,2,4-benzenetriol.

PMID- 14599449
TI  - A review of in vitro methods to assess the biological activity of tobacco smoke
      with the aim of reducing the toxicity of smoke.
AB  - In the last few years tobacco companies have been developing several research
      strategies in order to reduce the risks associated with smoking. These strategies
      include, for example, the refining of alternative cigarette designs that reduce
      the amount of hazardous chemicals in the mainstream smoke by introducing modified
      filters, and/or reducing the amount of biologically significant ingredients in
      tobacco-burning cigarettes. In the last few decades numerous studies have been
      published to assess the biological activity of tobacco smoke using in vivo and in
      vitro test systems. In this scenario a general scientific consensus on how to
      measure and characterize the risk associated with cigarette smoke is still
      lacking. Short-term in vitro assays, which are widely accepted by regulatory
      agencies around the world, are useful tools to evaluate both the biological
      activity and the progress towards a reduction of tobacco smoke toxicity. These
      assays could be mainly applied to evaluate cytotoxicity and genotoxicity
      properties on whole cigarette smoke as well as condensates or fractions of whole
      smoke. Cytotoxicity induction can be measured as cellular viability and growth
      rates using different end-points. Otherwise, the target of genotoxicity studies
      is the DNA molecule. For genotoxicity evaluation, the end-points and cell systems
      should be chosen from those that are relevant and appropriate as clinical
      surrogate markers. In this respect, the occurrence of early biological effect
      markers, such as mutational or clastogenic events (point mutations, frameshifts,
      micronuclei, SCE, DNA adducts) in bacterial and mammalian cells should be studied
      in a tiered approach following the guidelines of regulatory agencies. The choice
      of criteria shall be matter of discussion.

PMID- 14599450
TI  - Use of the microorganism Bacillus stearothermophilus as a model to evaluate
      toxicity of the lipophilic environmental pollutant endosulfan.
AB  - Microorganisms are very powerful tools for the supply of information about the
      toxic effects of lipophilic compounds, since an impairment of cell growth usually
      occurs as a result of perturbations related, in most cases, with the partition of
      toxicants in membranes. The thermophilic eubacterium Bacillus stearothermophilus
      has been used as a model system to identify alpha- and beta-endosulfan
      interactions with the membrane possibly related with the insecticide toxicity.
      Two approaches have been pursued: (a) bacterial growth is followed and the
      effects of endosulfan isomers determined; (b) biophysical studies with the
      fluorescent fluidity probe 1,6-diphenyl-1,3,5-hexatriene (DPH) were performed to
      assess the effects of alpha- and beta-endosulfan on the organization of the
      membrane lipid bilayer. The effects on growth were quantitatively evaluated by
      determination of growth parameters, namely the lag phase, the specific growth
      rate and the cell density reached by cultures in the stationary phase. Growth
      inhibition by alpha and beta-endosulfan dependent on the concentration is
      diminished or removed by the addition of 2.5 mM Ca2+ to bacterial cultures.
      Fluorescence DPH polarization consistently showed opposite effects of Ca2+ and
      alpha- and beta-endosulfan on the physical state of bacterial polar lipid
      dispersions.

PMID- 14599452
TI  - Dynamic monitoring of glutathione redox status in UV-B irradiated reconstituted
      epidermis: effect of antioxidant activity on skin homeostasis.
AB  - An "oxidative stress" should be considered as the consequence of a disbalance
      within the cutaneous tissue, between pro-oxidant processes and effective
      antioxidant defence systems and finally the result of a detrimental disturbance
      of the "cellular redox homeostasis". Instead of monitoring some particular
      impairment or a specific biological target of oxidative stress, it is preferable
      to examine the global effect of a stress, which is revealed by a loss of cellular
      homeostasis. The measurement of glutathione (relative amount of reduced (GSH), an
      oxidized form (GSSG)), offers a suitable approximation of the cellular redox
      status,since glutathione plays a pivotal role in the biological antioxidant
      systems. It is involved in the "first line " defence systems but also in
      repairing and recycling systems. This work aimed to develop an in vitro model
      that enables the dynamic monitoring of the glutathione redox status after UV-B
      irradiation. The method was performed in a commercially available Reconstituted
      Human Epidermis (RHE) model characterized by an high histo-morphological
      correspondence with normal human skin and by a very good inter batch
      reproducibility. With this experimental design it was possible to assess both the
      "physiological " behaviour of the epidermis after irradiation and also the
      ability of a tested ingredient to preserve or to restore the redox cutaneous
      homeostasis. The epidermis were irradiated and allowed to different recovery time
      (1,5,8,24 h) After each recovery time the quantification of GSH and GSSG by HPLC
      has been performed on RHE homogenates prepared in carefully controlled
      conditions. A series of non treated epidermis has been used as reference control.
      The redox homeostasis loss (e.g. GSH depletion) has been observed immediately
      after irradiation and remained between 1 and 5 h, although partial recovery takes
      place. In the presence of antioxidant actives the GSH depletion was minimised,
      and a faster restoration of homeostasis has been observed. The GSH/GSSG ratio was
      differentially modified by the actives tested, providing important insights into
      their specific mechanism of action. The glutathione redox status appears a very
      sensitive sensor, and kinetic studies have correlated protection against
      oxidative stress with redox homeostasis preservation.

PMID- 14599451
TI  - Evaluation of oxidative damage and inhibition of DNA repair in an in vitro study
      of nickel exposure.
AB  - It has been suggested that Nickel is involved in oxidative damage and inhibition
      of DNA repair. We studied the effects of NiSO4 on oxidative stress and DNA repair
      in Jurkat cells to elucidate its mechanism of action. Cells were treated with
      H2O2 and ROS generation (by flow cytometry), and oxidative DNA damage (as tail
      moment by Fpg-enzyme comet test), were evaluated immediately and after 4 and 24 h
      of DNA damage recovery occurred in presence or absence of NiSO4 (0.017 and 0.17
      microM) to clarify possible interactions of Ni with DNA repair processes.
      Moreover, cells were exposed to the same doses of NiSO4 for 4 and 24 hours to
      evaluate its direct oxidative effect. The results of the comet test showed high
      tail moment immediately after oxidative burst with a decreasing after 4 h of DNA
      recovery, and a slight increase after 24 h of recovery. The decreases were more
      limited for cells treated with NiSO4 0.17 microM indicating an inhibition of
      oxidative DNA damage repair by this substance. An induction of ROS was observed
      after 4 h of incubation with higher dose of NiSO4. Cells treated with H2O2 showed
      the highest level of ROS after 4 h of recovery in presence of NiSO4 0.17 microM
      that remained at elevated levels also after 24 h of recovery suggesting a
      synergistic action of Ni with H2O2 in the reduction of cellular anti-oxidative
      defence activities.

PMID- 14599453
TI  - Preparation of equine isolated hepatocytes.
AB  - In this study a detailed description of the equine hepatocyte isolation procedure
      is presented. Livers were obtained from horses slaughtered at the local
      slaughterhouse. For blood removal and liver preservation the following steps are
      suggested: perfusion with the oxygenated HBSS (0-2 degrees C, with continuous
      flow of 500-800 ml/min for 3-6 min), protection from ischemia injury by flushing
      with ice-cold University of Wisconsin Solution (UW, flow rate of 500-800 ml/min),
      and finally immersion of the liver lobe in UW solution (2 degrees C) during its
      transport to the laboratory. For equine isolated hepatocyte preparation a "three
      step" perfusion procedure was elaborated: rewarming, chelating and collagenase
      perfusion. We found optimal cell yield and viability under the following
      conditions: rewarming with UW (38 degrees C) for 8-14 min, chelating with calcium
      free Hanks' Balanced Salt Solution (HBSS, 38 degrees C) supplemented with 1 mM
      ethylene glycol-bis[beta-aminoethyl esther]-N,N,N'N'-tetracetic acid at the flow
      rate of 450 ml/min for 6 min and enzymatic digestion with HBSS supplemented with
      0.1% collagenase at 38 degrees C and 450 ml/min flow rate for 8-27 min. These
      conditions consistently generated cell harvests of 21 x 10(6)+/-4.86 cells/g of
      perfused liver tissue with viability of 82.7%+/-10.2.

PMID- 14599454
TI  - Tamoxifen induces ultrastructural alterations in membranes of Bacillus
      Stearothermophilus.
AB  - Tamoxifen (TAM), a non-steroid antiestrogen, is the mostly used drug for
      chemotherapy and chemoprevention of breast cancer. However, the mechanisms by
      which TAM inhibits cell proliferation in breast cancer are not fully understood.
      TAM strongly incorporates in biomembranes and a variety of effects have been
      assigned to biophysical and biochemical interactions with membranes. Therefore, a
      better understanding of the physicochemical basis of interaction of TAM with
      biomembranes is essential to elucidate the molecular mechanisms of action. A
      strain of Bacillus stearothermophilus has been used as a model to clarify the
      interaction of TAM with the cell membrane. TAM effects on the ultrastructure of
      membranes of this bacterium were evaluated by electron microscopy. Important
      ultrastructural alterations were observed in B. stearothermophilus treated with
      TAM, namely change in the geometry of the membrane profile from asymmetric to
      symmetric, disaggregation of ribosomes, coagulation of the cytoplasmic matrix,
      occurrence of mesossomes, appearance of fractures in membranes and the alteration
      of the ultrastructure of cell wall. These ultrastructural alterations confirm
      that TAM is a membrane-active drug and that membrane damage may be involved in
      molecular mechanisms of cell death induced by this drug.

PMID- 14599455
TI  - Molecular mechanisms of the metabolite 4-hydroxytamoxifen of the anticancer drug
      tamoxifen: use of a model microorganism.
AB  - A strain of the thermophilic eubacterium Bacillus stearothermophilus was used as
      a model system to identify membrane mediated cytotoxic effects of 4
      hydroxytamoxifen, following previous studies with tamoxifen. With this
      experimental approach we attempted to further clarify tamoxifen and 4
      hydroxytamoxifen membrane interactions often evoked as responsible for their
      multiple cellular effects. Bacterial growth and the oxygen consumption rate
      provided quantitative data of the cytotoxic action of hydroxytamoxifen. The
      effects of hydroxytamoxifen on the physical properties of bacterial lipid
      membrane preparations were also evaluated by fluorescence polarization of 1,6
      diphenyl-1,3,5-hexatriene. Cultures of B. stearothermophilus grown in a complex
      medium containing hydroxytamoxifen in the concentration range of 1 to 7 microM
      exhibited progressively longer lag adapting periods, decreased specific growth
      rates and lower growth yields, as compared to control cultures. Hydroxytamoxifen
      also affected the electron redox flow of B. stearothermophilus protoplasts and
      induced significant perturbation of the structural order of bacterial lipid
      dispersions. We concluded that the bacterial model provides useful information
      about the nature and repercussion of membrane physical interactions of this
      lipophilic drug, on the basis of an easy and economic methodology.

PMID- 14599457
TI  - Semi-automatic quantitative RT-PCR to measure CYP induction by drugs in human
      hepatocytes.
AB  - An assay has been developed for the quantitative measurement of CYP mRNA content
      of the major human isoforms (1A1, 1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1, 3A4 and
      3A5) in human hepatocytes. The method is based on the conversion of mRNAs into
      their corresponding cDNAs, followed by PCR amplification using appropriate
      primers. Making use of appropriate internal and external standards it is possible
      to estimate changes in CYP mRNA content of hepatocytes. The technique has been
      standardised to run semi-automatically. This procedure can be used to assess the
      CYP induction potential of new pharmaceuticals at a pre-clinical stage of
      development. To this aim, human hepatocytes obtained from functional liver tissue
      are incubated with the drugs for 50 h. Total RNA is extracted from culture and
      the cDNA is prepared by reverse transcription using high fidelity reverse
      transcriptase. Using appropriate primers, selective amplification of each CYP
      cDNA is achieved and real-time quantified by SYBR-Green fluorescence measurement.
      The extent of CYP induction obtained with the tested compounds is compared with
      the induction obtained with CYP model inducers (methylcholantrene, phenobarbital
      and rifampicin). This technique can be of value, to considerably simplify the
      identification of drug candidates with potential CYP inducing ability in man.

PMID- 14599456
TI  - Tribromophenol induces the differentiation of SH-SY5Y human neuroblastoma cells
      in vitro.
AB  - Tribromophenol is a pesticide with fungicide activity, presently used as a
      replacement of pentachlorophenol as a wood preservative, and as a flame retardant
      in electronic and electrotechnical devices. Retinoic acid differentiated and non
      differentiated SH-SY5Y human neuroblastoma cell cultures were exposed to a range
      of concentrations of tribromophenol for 24, 48 and 72 h and the effects evaluated
      at morphological, basal cytotoxicity and biochemical levels. Neuroblastoma cell
      number, evaluated by quantification of total protein content, was increasingly
      inhibited in accordance with the concentration of tribromophenol and the exposure
      time period. According to the mean effective concentrations, differentiated
      cultures were nearly three times more sensitive than naive cells. Lysosomal
      function evaluated by the neutral red uptake was stimulated, particularly in non
      differentiated cells. MTS metabolization was stimulated by all the treatments,
      with more potency at 24 h for differentiated cells. Acetylcholinesterase activity
      increased with the time of exposure in non-differentiated cells, while in
      differentiated cells the activity was doubled at 24 h. Morphological alterations
      were evident from 12.5 microM, showing hydropic degeneration and reduction in
      cell number, and from that concentration, piknosis and apoptotic bodies were
      observed. In conclusion, the main effects detected for tribromophenol were the
      induction of neuroblastoma cell differentiation, as expressed by the inhibition
      of cell growth and the increase in acetylcholinesterase activity with a critical
      cell concentration of 0.1 microM. Apoptosis was observed at high concentrations.
      The induction of cell differentiation and the special sensitivity of
      differentiated cells can explain some mechanisms involved in the embryotoxic and
      foetotoxic potential of tribromophenol.

PMID- 14599458
TI  - In vitro studies on DNA-photosensitization by different drug stereoisomers.
AB  - The possible stereoselectivity in DNA-photosensitization by carprofen (a NSAID
      drug) and ofloxacin (a fluoroquinolone agent) was investigated. The different
      drug stereoisomers or racemic mixtures were UVA-irradiated and the relaxation of
      the supercoiled circular pBR322 quantified by electrophoresis. Formation of
      single strand breaks was compared for each group of compounds. Moreover a
      mechanistic study by means of repair enzymes: T4 endonuclease V (specific of
      cyclobutane pyrimidine dimers), E. coli endonuclease III (revealing oxidized
      pyrimidines) and E. coli Formamidopyrimidine-DNA glycosylase (revealing oxidized
      purines) provided further insights into a possible stereoselectivity of the
      different reaction pathways in drug photosensitized-DNA damage. Ofloxacin and
      levofloxacin (its S stereoisomer) were responsible of single strand breaks
      formation as well as oxidation of pyrimidine and purine bases. No pyrimidine
      dimers were observed. Racemic, R and S stereoisomers of carprofen were less
      efficient than ofloxacin in DNA single strand breaks formation and did not induce
      enzyme-sensitive sites. The photoproducts distribution of drug-photosensitized
      reactions of 2'-deoxyguanosine and thymidine were established by HPLC as
      fingerprints for assignment of the DNA-photosensitization mechanism. Both Type I
      and Type II mechanisms were assigned to nucleoside-photosensitization by
      ofloxacin and levofloxacin. In the case of carprofen, a weak nucleoside
      degradation was obtained. The data suggest that levofloxacin, the (S)
      stereoisomer, might be slightly more efficient than racemic ofloxacin. In the
      case of carprofen the (S) isomer appears to be somewhat less active than its (R)
      enantiomer. However, due to the small differences found, the possible
      stereoselectivity has to be confirmed by future studies.

PMID- 14599459
TI  - Study of the potential cytotoxicity of dental impression materials.
AB  - The aim of this study was to assess the cytotoxicity of tow types of impression
      dental materials: polyethers (Impregum Penta, Permadyne Penta Heavy and Light)
      and vinyl polysiloxanes (Elite Mono Tray, Medium, Low viscosity and Elite H-D
      Putty). Their cytotoxic effects were studied by indirect and direct tests. The
      indirect tests were performed by incubating impression materials in serum free
      cell culture medium to prepare the soluble extracts. Balb/c 3T3 cells were
      incubated with extract dilutions (25, 50, 75 and 100%) for 24 h. The extracts of
      polyether materials caused a decrease of cellular viability, evaluated by light
      microscopy, by cell counting and by MTT test. The extracts of vinyl polysiloxanes
      materials induced a slight effect on cellular number and viability. The direct
      tests were performed by placing the impression materials in the centre of Petri
      dishes while Balb/c 3T3 were settling. The cellular proliferation was drastically
      reduced by polyethers and it was unaffected by the presence of vinyl
      polysiloxanes. These results show that: (a) the polyether materials are more
      toxic than vinyl polysiloxanes in our experimental conditions, (b) the impression
      materials are cytotoxic to the same degree in all assay methods.

PMID- 14599461
TI  - Use of CFU-GM assay for prediction of human maximum tolerated dose of a new
      antitumoral drug: Yondelis (ET-743).
AB  - Acute cytotoxic exposure causes decreases in bone marrow progenitors that
      precedes the neutrophil nadir. Experiments in animal models reveal a relationship
      between the reduction in granulocyte-macrophage progenitors (CFU-GM) and the
      decrease in absolute neutrophil count [Toxicol. Pathol. 21 (1993) 241]. Recently,
      the prevalidation of a model for predicting acute neutropenia by the CFU-GM assay
      has been reported [Toxicol. In Vitro 15 (2001) 729]. The model was based on
      prediction of human MTD by adjusting the animal-derived MTD for the differential
      sensitivity between CFU-GM from animal species and humans. In this study, this
      model has been applied on a new antitumoral drug, Yondelis (Ecteinascidin; ET
      743). Preclinical studies showed that hematotoxicity was the main side effect in
      mice, being the MTD of 600 microg/m2 [Drugs Future 21 (1996) 1155]. The
      sensitivity of myeloid progenitors was higher in mice than in humans, with IC90
      values of 0.69+/-0.22 nM and 1.31+/-0.21 nM for murine and human CFU-GMs
      respectively. This study predicts a human MTD of 1145 microg/m2. The reported
      human MTD of ET-743 given as a 24-h continuous infusion every 3 weeks is 1800
      microg/m2 [J. Clin. Oncol. 19 (2001) 1256]. Since our predicted MTD is within
      fourfold of the actual MTD (the interspecies variation in tolerated dose due to
      differences in clearance rates, metabolism pathways and infusion rate) the result
      confirms the profit of the prediction model.

PMID- 14599460
TI  - Comparison of the changes in adenine nucleotides of rat liver mitochondria
      induced by tamoxifen and 4-hydroxytamoxifen.
AB  - The antiestrogen tamoxifen (TAM) inhibits the growth of different estrogen
      receptor (ER)-negative cells. Recently, multiple effects of TAM on mitochondrial
      bioenergetic functions have been pointed to explain its ER-independent cell death
      mechanisms. We have shown that TAM and its major active metabolite 4
      hydroxytamoxifen (OHTAM) induce depolarization of the mitochondrial membrane
      potential (DeltaPsi) and uncouple the mitochondrial respiration, depressing the
      oxidative phosphorylation efficiency. To clarify the biochemical mechanisms
      underlying the changes in the regulation of ATP synthesis and yield, in this work
      we evaluated the alterations of mitochondrial adenine nucleotides induced by both
      drugs and ascertained whether such changes could reflect a specific inhibition of
      either the adenine nucleotide translocase (ANT) or the phosphate carrier, as well
      as the activation of ATP hydrolysis due to DeltaPsi depolarization. We found that
      both antiestrogens caused a concentration-dependent decrease in mitochondrial ATP
      levels. Mitochondrial ADP and AMP were concomitantly increased with a subsequent
      decrease in the ATP/ADP or ATP/AMP ratios. The total concentration of adenine
      nucleotides also changed. Additionally, both drugs decreased the ANT content of
      mitochondria, inhibited the phosphate carrier and induced ATP hydrolysis.
      However, the effects of TAM were more drastic than those induced by OHTAM.
      Therefore, the depletion of ATP might result from an activation of ATP
      catabolism, as well as from a decrease in the mitochondrial content of ANT and
      partial inhibition of the phosphate carrier. Our data may explain the ER
      independent effects and cytotoxicity of both drugs and, in agreement with other
      previous studies, suggest that OHTAM is much less toxic to mitochondria than TAM.

PMID- 14599462
TI  - Diclofenac induces apoptosis in hepatocytes.
AB  - Hepatotoxicity is one of the side effects associated with the administration of
      diclofenac, a non-steroidal anti-inflammatory drug widely used clinically. The
      effect of diclofenac on the early events that trigger apoptosis cascade have been
      evaluated in rat hepatocytes. To do this, early and late apoptotic markers,
      associated with the pivotal steps of the execution phase, have been evaluated
      after incubation with the drug. The results show that the apoptotic effect of
      diclofenac occurs after exposure to sub-cytotoxic concentrations of the drug
      (maximal non toxic concentration, MNTC, after 24-h treatment was 450 microM),
      without overlapping with cell necrosis (LDH leakage evaluation). Flow cytometric
      analysis revealed a time- and dose-dependent increase of apoptotic nuclei with
      sub-diploid DNA content. Caspase 3 activation (3-5-fold control) was maximal
      after 12 h of exposure to 350 microM of the drug. The involvement of the
      mitochondrial permeability transition (MPT) in diclofenac-induced apoptosis was
      investigated. Cyclosporine A and decylubiquinone, MPT specific inhibitor,
      prevented the activation of caspase 3, thus showing that diclofenac opened the
      MPT pore. Treatment of hepatocytes with antioxidants (alpha-tocopherol, N,N
      dimethylthiourea, superoxide dismutase) were able to prevent caspase cascade
      activation by diclofenac, revealing that oxidative stress at the mitochondrial
      level is involved in MPT induction. Finally, the differential cytotoxic and
      apoptotic effect produced in hepatocytes and non-metabolizing hepatoma cells
      suggest that CYP-mediated metabolism of diclofenac apoptosis may be related to
      the apoptotic effect of the drug.

PMID- 14599463
TI  - Hepatic (dys-)function during inflammation.
AB  - It is an understatement to say that the liver is an important organ. Each of the
      liver cells goes through thousands of complex biochemical interactions that
      influence all of the other organs in the body. Since the liver is involved with
      almost all biochemical processes it is no wonder that there are many different
      diseases that will affect it. A process known to impair liver function, including
      hepatic drug metabolism, is an infection induced inflammatory response. Infection
      induced alterations in liver function involve various cell types and their
      continuous cross-talk, as well as several circulating or locally secreted
      inflammatory mediators. Three main hepatic cell types contribute to the liver
      response during inflammation: hepatocytes, Kupffer cells and sinusoidal
      endothelial cells. In addition, activated neutrophils, which are also recruited
      in the liver and produce potentially destructive enzymes and oxygen-derived
      radicals, may further enhance liver injury. This review will focus on the pathway
      by which Kupffer cells and hepatocytes are activated and how this affects liver
      function, in particular hepatic drug metabolism.

PMID- 14599464
TI  - Down regulation of humoral immunity in chickens due to carbendazim.
AB  - This study was planned to investigate the effect of very low dose of carbendazim
      on the humoral immune response in the chicken. Sixteen adult chickens, earlier
      vaccinated against New Castle Disease were divided in two experimental groups.
      Chickens of group I served as control, while group II birds were given a feed
      containing 200 ppm of carbendazim, which is considered no observable effect level
      (NOEL) dose, for a period of 6 months. The Humoral immune response was measured
      by the B-lymphocyte blastogenesis assay using lipopolysaccharide as mitogen and
      the quantitation of IgG, IgA, IgM levels by using respective antichicken
      conjugates, through an ELISA method. Total serum proteins, serum gamma-globulins
      and globulins were measured using commercially available kits. Carbendazim
      significantly (P< or =0.05) reduced both the B-lymphocyte proliferation and serum
      IgG, IgM and IgA levels, leading to decreased immunocompetence. At the end of
      experiment percent decrease in B-lymphocyte proliferation was 20.5% and that in
      serum IgG, IgM and IgA were 11.2, 22.9 and 28.8%, respectively. The percent
      decrease in total serum protein, serum gamma-globulins and serum globulins were
      14.6, 18.5 and 9.7%, respectively. Results clearly indicated down regulation of
      humoral immunity by carbendazim at NOEL dose.

PMID- 14599465
TI  - Isolated human hepatocytes in culture display markedly different gene expression
      patterns depending on attachment status.
AB  - In vitro human hepatocyte cultures are a key tool in the investigation of
      xenobiotic toxicity and metabolism. In most in vitro hepatocyte studies, the
      cells are allowed to adhere to an extracellular matrix, such as collagen.
      Unfortunately, the ability of freshly isolated hepatocytes to adhere to collagen
      varies from donor to donor. We used microarray analysis to determine what gene
      expression differences exist between hepatocytes in suspension and hepatocytes
      attached to collagen. Results from different donors showed a considerable
      difference in gene expression patterns between the two hepatocyte populations. In
      addition, we also compared the gene expression profiles of hepatocytes in culture
      with liver tissue. The results showed that both hepatocytes in suspension and
      hepatocytes attached to collagen display significant gene expression differences
      compared with liver tissue. Finally, we show that both populations of hepatocytes
      are responsive to dexamethasone and regulate some of the same genes. Overall, our
      results suggest that either significant gene expression changes occur in isolated
      hepatocytes or that suspended and attached cells represent different populations
      of hepatocytes found in intact livers.

PMID- 14599466
TI  - High throughput screening (HTS) for phototoxicity hazard using the in vitro 3T3
      neutral red uptake assay.
AB  - Testing for phototoxic hazard is usually carried out for product ingredients
      intended for use on skin, which may be exposed to sunlight. Unilever currently
      uses the validated in vitro 3T3 Neutral Red Uptake phototoxicity test (NRU PT).
      This protocol involves 2-3 experiments, each taking 3 days to perform. One person
      can test up to seven test materials plus positive control at any one time,
      requiring approximately 0.5 g test material. Higher throughput is required where
      libraries of potential actives are being generated and screening for potential
      phototoxicants is required. A proposed HTS protocol would use the NRU PT, but
      only one concentration (10 microg/ml) in a single experiment. The validity of the
      HTS protocol was investigated by a retrospective examination of data from 86
      materials previously tested. Phototoxic hazard predictions made using the
      conventional NRU PT were compared with those obtained if only data at 10
      microg/ml were considered. A majority of 73 materials (84.9%) gave agreement in
      predictions between the two protocols; for 13 materials (15.1%) the assessments
      did not agree. There were no false positives; however, there were some false
      negatives, i.e., predicted as phototoxic from the conventional assay, but non
      phototoxic at 10 microg/ml. As this protocol is intended for screening purposes
      only it is considered that this would be acceptable at this stage in material
      selection. One person could screen 128 test materials in 3 days, requiring <1 mg
      test material, giving a substantial increase in productivity. Any material
      selected for further development and inclusion in a formulation may require
      further confirmatory testing, e.g. using a human skin model assay for
      phototoxicity.

PMID- 14599467
TI  - A yeast-based method for the detection of cyto and genotoxicity.
AB  - A miniaturized short-term in vivo genotoxicity screening assay based on
      genetically modified yeast (Saccharomyces cerevisiae) cells was performed to
      explore the capacity of this eukaryotic organism to detect the presence of
      genotoxic compounds. An increased general sensitivity of yeast cells to toxic
      compounds was obtained by using a strain being deleted in the prominent
      pleiotropic drug resistance mediating efflux transporters PDR5, SNQ2 and YOR1. In
      order to detect genotoxic effects, a yeast optimized version of the green
      fluorescent protein (GFP) was fused to the RAD54 promoter that is activated upon
      DNA damage. Various model substances including the oxygenated fuel additive
      methyl tertiary-butyl ether (MTBE) and the direct acting genotoxins methyl-N
      nitro-N-nitrosoguanidine (MNNG) and 4-nitroquinoline-1-oxide (4-NQO) were tested.
      All model substances were in parallel examined for chronic cytotoxicity. The
      results point out the sufficiency of both the sensitivity of the yeast cells to
      detect chronic cytotoxicity and the intensity of the fluorescence signal for the
      assessment of genotoxic effects. Thus, the test enables simultaneous detection of
      cytotoxic and genotoxic effects. By partial automation and implementation of the
      test in the microtitre scale this bioassay allows parallel sensitive pre
      screening of numerous samples.

PMID- 14599468
TI  - In-house assessment of a modified in vitro cytotoxicity assay for higher
      throughput estimation of acute toxicity.
AB  - The main objective of this study was to assess an in-house 3T3 NRU cytotoxicity
      assay for compatibility with a prediction model for acute rodent oral toxicity
      endorsed by an NIEHS-ICCVAM workshop. The aim is to use the NRU assay as one test
      component of HTS strategies for both acute oral toxicity and acute skin
      irritation, enabling the rejection of the most toxic materials and prioritisation
      of other materials for further testing. Groups of model cytotoxins and irritants
      were tested using the NRU assay and their EC50 values obtained from dose-response
      curves. These values were compared with those estimated from a limited (three)
      dose protocol, deemed more suitable for HTS. A good correlation was observed
      between the EC50 values from both dose-response curves (R2=0.94). The
      relationships between EC50 values and acute rodent oral toxicity were compared by
      application of the prediction model to the model cytotoxins. The results from
      both full and limited dose-responses fitted within the acceptance limits of the
      prediction model, with regression lines similar to that of the model. Results
      indicated that the performance of the currently used 3T3 NRU cytotoxicity assay
      was similar to that of the assays used to generate the data employed in
      developing the prediction model. This prediction model can be applied with both
      the standard and HT assays to estimate acute rodent oral toxicity.

PMID- 14599469
TI  - Initial in vitro toxicity testing of functional foods rich in catechins and
      anthocyanins in human cells.
AB  - Functional foods need to be assessed for beneficial effects to support claims,
      but also for toxic effects. This report describes two examples of how complex
      food samples are initially characterized in human cells in vitro. Water extracts
      of green tea (GT) and black carrots (BC) were analyzed for key ingredients
      (catechins and anthocyanidins, respectively). Extracts, reconstituted mixtures of
      the major ingredients or individual compounds [(-)-epigallocatechin gallate or
      cyanidin, respectively] were evaluated in parallel using human colon cells (HT29
      clone 19A). End points of cytotoxicity included determination of membrane
      integrity, proliferation inhibition, and genetic damage. Cells were pretreated
      with plant compounds at sub-toxic concentrations, and their resistance to
      toxicity of H2O2 was evaluated as a parameter of protection. The extracts reduced
      cell viability (BC) and cell growth (BC, GT) and caused DNA damage (BC, GT). They
      were more toxic than their key ingredients. Neither GT-samples nor BC protected
      against H2O2-induced DNA damage, whereas cyanidin did. In vitro analysis of
      extracts from functional foods firstly aims at defining the sub-toxic
      concentrations at which protective activities are then further characterized. It
      also allows comparing responses of complex samples and individual compounds,
      which is important since effects from protective food ingredients can be masked
      by accompanying toxic components.

PMID- 14599470
TI  - Use of in vitro assays to assess the potential antigenotoxic and cytotoxic
      effects of saffron (Crocus sativus L.).
AB  - Saffron is harvested from the dried, dark red stigmas of Crocus sativus L.
      flowers. It is used as a spice for flavoring and coloring food and as a perfume.
      It is often used for treating several diseases. We assessed the antimutagenic,
      comutagenic and cytotoxic effects of saffron and its main ingredients using the
      Ames/Salmonella test system, two well known mutagens (BP, 2AA), the in vitro
      colony formation assay and four different cultured human normal (CCD-18Lu) and
      malignant (HeLa, A-204 and HepG2) cells. When only using the TA98 strain in the
      Ames/Salmonella test system, saffron showed non-mutagenic, as well as non
      antimutagenic activity against BP-induced mutagenicity, and demonstrated a dose
      dependent co-mutagenic effect on 2-AA-induced mutagenicity. The saffron component
      responsible for this unusual comutagenic effect was safranal. In the in vitro
      colony formation test system, saffron displayed a dose-dependent inhibitory
      effect only against human malignant cells. All isolated carotenoid ingredients of
      saffron demonstrated cytotoxic activity against in vitro tumor cells. Saffron
      crocin derivatives possessed a stronger inhibitory effect on tumor cell colony
      formation. Overall, these results suggest that saffron itself, as well as its
      carotenoid components might be used as potential cancer chemopreventive agents.

PMID- 14599471
TI  - In vitro assay for human toxicity of cereulide, the emetic mitochondrial toxin
      produced by food poisoning Bacillus cereus.
AB  - The in vitro boar spermatozoon test was compared with the LC ion trap MS analysis
      for measuring the cereulide content of a pasta dish, implemented in serious
      emetic food poisoning caused by Bacillus cereus. Both assays showed that the
      poisonous food contained approximately 1.6 microg of cereulide g(-1) implying the
      toxic dose in human as < or =8 microg kg(-1) body weight. The threshold
      concentration of cereulide provoking visible mitochondrial damage in boar sperm
      exposed in vitro was 2 ng of cereulide ml(-1) of extended boar sperm. The same
      threshold value was found for cereulide extracted from the food and from the
      cultured bacteria. This shows that other constituents of the food did not enhance
      or mask the effects of cereulide. Exposure of four human cell lines (HeLa, Caco
      2, Calu-3 and Paju) to cereulide showed that the threshold concentration for the
      loss of mitochondrial membrane potential in human cells was similar to that
      observed in boar sperm. Human cells and boar sperm were equally sensitive to
      cereulide. The results show that boar spermatozoan assay is useful for detecting
      cereulide concentrations toxic to humans. Spermatozoa in commercially available
      extended fresh boar and cryopreserved bull semen were compared, boar sperms were
      100 times more sensitive to cereulide than bull sperms.

PMID- 14599472
TI  - A new method for in vitro detection of microbially produced mitochondrial toxins.
AB  - Sperm motility inhibition assay, earlier shown valuable for the detection of food
      poisoning non-protein toxins of Bacillus species was developed into an assay
      useful for specific detection of mitochondria damaging toxins. This was done by
      assessing the dissipation of the mitochondrial inner membrane transmembrane
      potential, Deltapsim under conditions where the plasma membrane permeability
      barrier remained intact. The Deltapsim was estimated as the intensity of orange
      JC-1 fluorescence in the mitochondrial sheath of the exposed spermatozoa. The
      plasma membrane integrity of the same cells was assessed by observing the
      exclusion of propidium iodide from the cytoplasm. Three types of mitochondrial
      toxic responses to microbially made bioactive substances were recognised.
      Mitochondrial toxicity by gramicidin (A, B, C, D), nigericin, salinomycin,
      narasin, monensin, calcimycin and antimycin A was characterised by gradual fading
      of the JC-1 fluorescence in the mitochondria. Dissipation of the Deltapsim by
      cereulide, valinomycin and enniatin (A, A1, B, B1) was visible as spotwise
      quenching of the mitochondrial JC-1 fluorescence. In addition these substances
      caused hyperpolarisation of the plasma membrane. Oligomycin (A, B, C), ionomycin
      and staurosporine inhibited the spermatozoan motility, but Deltapsim was fully
      preserved. Surfactin and lichenysin A caused mitochondrial damage at
      concentrations where the plasma membrane was also damaged.

PMID- 14599474
TI  - Permeability characteristics of parental and clonal human intestinal Caco-2 cell
      lines differentiated in serum-supplemented and serum-free media.
AB  - The aim of this study was to define the permeability characteristics of the
      parental Caco-2/ATCC cell line and of three clonal lines (Caco-2/TC7, Caco-2/AQ,
      Caco-2/15) differentiated in serum-supplemented or in serum-free defined medium.
      The Caco-2 cells were grown in DMEM supplemented with either 10% foetal calf
      serum or insulin-transferrin-selenium and lipids (cholesterol, palmitic acid,
      oleic acid) for up to 24 days after seeding on polyethylene terephthalate filter
      inserts (1 microm pore diameter). The permeability of the cell monolayer was
      assessed by measuring trans-epithelial electrical resistance (TEER) and the
      apparent permeability (Papp) of the extracellular marker mannitol during
      differentiation from day 6 until day 24. In all lines TEER values increased
      during differentiation reaching a plateau value around day 15 after seeding,
      while the Papp for mannitol decreased sharply around day 8 and levelled off
      thereafter. Substantial differences were observed in the maximal TEER values
      achieved during differentiation in the four lines examined (Caco-2/TC7 <Caco
      2/ATCC<Caco-2/AQ<Caco-2/15), while the Papp for mannitol, upon differentiation,
      was not significantly different in all four lines. Media composition (serum
      supplemented vs. defined medium) did not generally affect the TEER (with the
      exception of the Caco-2/ATCC). Conversely, the presence of serum in the medium
      consistently lowered and stabilised Papp values as compared with defined medium.

PMID- 14599473
TI  - Protective effect of lipoic acid against hydrogen peroxide in yeast cells.
AB  - Lipoic acid (LA) is found in all kinds of cells, it is widely used in medicine
      and as a dietary supplement, and it is involved in different physiological
      functions. Even if there are many papers regarding therapeutic effects of LA,
      medical research does not always support its effectiveness and little is known
      about LA metabolism in eukaryotic cells. In this work the probable protective
      effect of LA was investigated employing five strains of yeast Saccharomyces
      cerevisiae through short term assays. In particular LA behaviour in oxidative
      stress conditions was studied. For this purpose hydrogen peroxide was used as
      oxidant. In D7 strain, LA showed antimutagenic effects against hydrogen peroxide
      and decreased significantly cytochrome P450. To better elucidate the effect of LA
      the following yeast strains carrying deletions in superoxide dismutase genes
      (SOD) were employed: EG-103 (wild type), EG-110 strain (without mytochondrial
      SOD), EG-118 (without cytoplasmatic SOD) and EG-133 (without both enzymes). LA
      increased the number of mitotic divisions in EG-103, EG-110 and EG-133 and in
      growing cells (EG-103, EG-110, EG-118) it increased survival percentage with
      respect to hydrogen peroxide. The positive action was evident in D7 and in EG
      strains and it showed that LA can be protective and antimutagenic against
      oxidants in yeast cells, via its antioxidant activity.

PMID- 14599475
TI  - Functionality of cultured human hepatocytes from elective samples, cadaveric
      grafts and hepatectomies.
AB  - The major possible sources of human liver for hepatocyte isolation are elective
      liver biopsies, cadaveric liver grafts and therapeutic liver resections. The
      suitability in terms of metabolic-competent hepatocyte cultures and risk/benefit
      of these resources has been comparatively studied. To this end, viability of
      isolated hepatocytes, yield of isolation procedure, hepatocyte survival during
      culture and CYP activities were the parameters analysed. The best results were
      found in hepatocytes prepared from elective biopsies, whereas a marked reduction
      in viability and functional competence was seen in hepatocytes from hepatectomy
      samples. Metabolic differences were observed in total CYP oxidative metabolism (7
      ethoxycoumarin O-deethylation, total testosterone hydroxylation), as well as in
      CYP3A4, CYP2C9 or CYP2C19 activities (testosterone oxidations at 6beta-, 16beta-
      and 17-positions, respectively). Vascular control during the hepatectomy
      procedure influenced hepatocyte functionality: higher CYP activities were found
      in hepatocytes isolated from samples obtained under non-ischemic conditions or
      continuous vascular clamping than in those obtained under intermittent vascular
      clamping. In addition to cellular functionality, other criteria such as sample
      availability or ethical aspects should be considered. Elective biopsies have low,
      but not absent, surgical risk. However, the better functionality and the higher
      accessibility of elective liver samples in comparison to the other groups suggest
      this source of liver tissue as the most appropriate for cell harvesting purposes.

PMID- 14599476
TI  - In vitro toxicity testing of supramolecular sensitizers for photodynamic therapy.
AB  - We report the phototoxicity of meso-tetrakis(4-sulphonatophenyl)porphine (TPPS4)
      and zinc metallocomplex (ZnTPPS4) sensitizers in the presence or absence of 2
      hydroxypropyl-beta-cyclodextrin (HP-beta-CD) on G361human melanoma cells.
      Morphological changes in cell cultures have been evaluated using inversion
      fluorescent microscope and image analysis. Viability of cells was determined by
      means of molecular probes for fluorescence microscopy (LIVE/DEAD kit- double
      staining with Calcein AM and Ethidium Homodimer). The quantitative changes of
      cell viability in relation to sensitizers concentrations and irradiation doses
      were proved by fluorometric measurement with fluoroscan Ascent. We found that the
      most effective sensitizer is ZnTPPS4 bound to HP-beta-CD, since the IC50 value
      was 12.5 g/ml at the dose of light radiation of 10 J/cm2.

PMID- 14599477
TI  - Ecopa: actual status and plans.
AB  - Ecopa, the European Consensus Platform on alternatives, is an international not
      for-profit organization, based in Belgium and complying with Belgium law. It is
      the only quadripartite organization at EU level, which is promoting the 3R
      Alternatives at the European level. Ecopa brings together National Consensus
      Platforms on alternative methods. Consensus means that all parties concerned are
      represented: animal welfare, industry, academia and governmental institutions.
      Ecopa actually counts 14 National Platforms of Member States (or future Member
      States), (8 full members, platforms of Austria, Belgium, Finland, Germany, The
      Netherlands, Spain, Switzerland and United Kingdom and six associate members
      being Czech Republic, Denmark, Italy, Norway, Poland and Sweden) and has three
      working groups. The fields of interest of these working groups change according
      to the needs and were until now concerned with (i) the 6th Framework Programme of
      the EC for Research, Technological Development and Demonstration Activities, (ii)
      the EC White Paper Strategy for a Future EU Chemicals Policy and (iii) the
      formation & educational programmes on alternative methods. Ecopa is thus uniquely
      placed and has huge expertise to offer to the debate around scientific and
      politically-linked topics. It has to be considered a key stakeholder by the
      European Commission and Parliament (http://ecopa.vub.ac.be) or
      http://ecopa.tsx.org).

PMID- 14599478
TI  - Optical response of the cultured bovine lens; testing opaque or partially
      transparent semi-solid/solid common consumer hygiene products.
AB  - This study determines the relative ocular lens irritancy of 16 common partially
      transparent or non-transparent consumer hygiene products. The irritancy was found
      by measuring the changes in the sharpness of focus [referred to as the back
      vertex distance (BVD) variability] of the cultured bovine lens using a scanning
      laser In Vitro Assay System. This method consists of a laser beam that scans
      across the lens, and a computer, which then analyses the average focal length
      (mm), the BVD variability (mm), and the intensity of the beam transmitted. Lenses
      were exposed to the 16 hygiene products and the lens' focusing ability was
      monitored over 192 h. The products are semi-solids or solids (e.g. gels, lotions,
      shampoos). They are categorized into six groups: shampoos, body washes, lotions,
      toothpastes, deodorant, and anti-perspirant. Damage (measured by > 1 mm BVD
      variability) occurred slower for the shampoos, especially in the case of baby
      shampoo. The results indicate that shampoos exhibit the lowest level of ocular
      lens toxicity (irritability) while the deodorant is the most damaging.

PMID- 14599479
TI  - The benefits of the 3T3 NRU test in the safety assessment of cosmetics: long-term
      experience from pre-marketing testing in the Czech Republic.
AB  - We have introduced the 3T3 NRU cytotoxicity test for methodological, economical
      and ethical reasons as a regular part of tier pre-marketing testing to assess
      local tolerance of raw materials for cosmetics, household chemicals and final
      cosmetic products. Using the 3T3 cell line according to the standard INVITTOX
      protocol No.64 (NRU Assay) the borderline concentration, relevant to the highest
      tolerated dose, is determined for each material. The toxic effect is reached at
      different concentration levels specific for individual cosmetics categories,
      depending on their chemical characteristics. Typical ranges of cytotoxicity for
      specific categories of cosmetics were established after testing of hundreds of
      materials. The range lies between 1 microg/ml (anti-dandruff shampoos), up to
      2000 microg/ml (toothpastes and mouthwashes). The 3T3 NRU cytotoxicity test is a
      sensitive tool able to identify more aggressive products, that are also more
      likely to evoke irritation in human skin. It was even possible to detect
      protective effects of one natural herbal ingredient. The comparative study of
      cytotoxicity test results and human patch test results from a group of essential
      oils is presented. Cytotoxicity tests represent a highly ethical approach for
      estimation of irritancy. On the basis of in vitro test results suggesting low
      risk we can proceed to confirmatory tests in human volunteers.

PMID- 14599480
TI  - Evidence for delayed cytotoxicity effects following exposure of rat hepatoma
      derived Fa32 cells: implications for predicting human acute toxicity.
AB  - The delayed cytotoxicity of the Multicentre Evaluation of In vitro Cytotoxicity
      (MEIC) reference chemicals was investigated in rat hepatoma-derived Fa32 cells.
      The cells were treated for 24 h with the test chemicals, and were than further
      cultured for 5 days in normal culture medium. The cytotoxicity was measured by
      the neutral red uptake inhibition, and the results were quantified by determining
      the NI50del. This is the concentration of test compound required to decrease the
      neutral red uptake with 50% compared with control cells. The results were
      compared with the acute NI50, the corresponding value measured immediately after
      24 h treatment of the cells. On a total of 44 chemicals, nine showed delayed
      cytotoxicity (NI50del lower than or equal to NI50), 11 a probably delayed, and 24
      no delayed cytotoxicity (NI50del more than 1.5 x NI50). When the NI50del was
      compared with human toxicity, a correlation coefficient r2=0.761 was obtained.
      For the same series of 44 chemicals this correlation was clearly higher than that
      for human hepatoma-derived Hep G2 cells (r2=0.695). The Hep G2 assay was the best
      acute in vitro assay for the prediction of human toxicity within the MEIC study.
      Consequently, the delayed cytotoxicity assay on cultured Fa32 cells has the best
      prediction value so far obtained for the human toxicity.

PMID- 14599481
TI  - Carcinogenic metal induced sites of reactive oxygen species formation in
      hepatocytes.
AB  - Severe chronic liver disease results from the hepatic accumulation of copper
      nickel, cobalt or iron in humans and on the other hand cadmium, dichromate and
      arsenic may induce lung or kidney cancer. Acute or chronic CdCl2, HgCl2 or
      dichromate administration induces hepatic and nephrotoxicity in rodents.
      Oxidative stress is often cited as a possible cause but has not yet been
      measured. For the first time we have measured the reactive oxygen species (ROS)
      formation induced when cells are incubated with metals and determined its source.
      Hepatocytes incubated with 2',7'-dichlorofluorescin diacetate resulted in its
      rapid uptake and deacetylation by intracellular esterases to form 2',7'
      dichlorofluorescin. A marked increase in ROS formation occurred with LD50
      concentrations of cadmium [Cd(II)], Hg(II) or arsenite [As(III)] which was
      released by proton ionophores that uncouple oxidative phosphorylation. Uncouplers
      or oxidative phosphorylation also inhibited ROS formation induced by these
      metals, which suggests that mitochondria are major contributors to endogenous ROS
      formation. Glycolytic substrates also inhibited Cd(II)/Hg(II)/As(III)-induced ROS
      formation and confirms that mitochondria are the site of ROS formation. By
      contrast ROS formation by LD50 concentrations of Cu(II), Ni(II), Co(II) or
      dichromate [Cr(VI)] were not affected by uncouplers or glycolytic substrates.
      However they were inhibited by lysosomotropic agents or endogenous inhibitors [in
      contrast to Hg(II), Cd(II) or As(III)]. Furthermore Cu(II), Ni(II), Co(II) or
      Cr(VI) accumulated in the lysosomes and the ROS formed caused a loss of lysosomal
      membrane integrity. The release of lysosomal proteases and phospholipases also
      contributed to hepatocyte cytotoxicity. ROS formation and cytotoxicity induced by
      added H2O2 or generated by the intracellular redox cycling of nitrofurantoin was
      also inhibited by lysosomotropic agents and ferric chelators suggesting that
      lysosomal Fe(II) contributes to H2O2-induced cytotoxicity. In conclusion,
      lysosomes are sites of cytotoxic ROS formation with redox transition metals
      (CuII, CrVI, NiII, CoII) whereas mitochondria are the ROS sites for non-redox or
      poor redox cycling transition metals (CdII, HgII, AsIII).

PMID- 14599482
TI  - Alterations in cholinergic and non-cholinergic neurotransmitter receptor
      densities in transgenic Tg2576 mouse brain with beta-amyloid plaque pathology.
AB  - Cholinergic deficits in Alzheimer's disease are accompanied by a number of
      alterations in other transmitter systems including glutamate, noradrenaline and
      serotonin, suggesting the involvement also of other neurotransmitter systems in
      the pathogenesis of the disease. To address the question whether beta-amyloid may
      contribute to these deficits, brain tissue from transgenic Tg2576 mice with
      Alzheimer plaque pathology at ages of 5 (still no significant plaque load) and 17
      months (moderate to high cortical beta-amyloid plaque load) were examined for a
      number of cholinergic and non-cholinergic markers. Transgenic mice with no
      significant plaque load demonstrated reduced hemicholinium-3 (HCh-3) binding to
      choline uptake sites in anterior brain regions as compared to non-transgenic
      littermates, while in aged transgenic mice with high number of plaque deposits
      decreased HCh-3 binding levels were accompanied by increased vesicular
      acetylcholine transporter binding in selected cortical brain regions. In aged
      transgenic mice GABA(A), NMDA, AMPA, kainate, and beta-adrenergic as well 5
      HT(1A)- and 5-HT(2A)-receptor binding levels were hardly affected, whereas
      alpha(1)- and alpha(2)-adrenoceptor binding was increased in selected cerebral
      cortical regions as compared to non-transgenic littermates. The development of
      changes in both cholinergic and non-cholinergic markers in transgenic Tg2576
      mouse brain already before the onset of progressive plaque deposition provides in
      vivo evidence of a modulatory role of soluble beta-amyloid on cortical
      neurotransmission and may be referred to the deficits in learning and memory
      observed in these mice also before significant plaque load.

PMID- 14599483
TI  - Bcl-2 family members make different contributions to cell death in hypoxia and/or
      hyperoxia in rat cerebral cortex.
AB  - Hypoxic brain injury during fetal or neonatal development leads to damaged
      immature neurons and can result in cognitive or behavioral dysfunction. Hyperoxia
      therapy (treatment with oxygen) is commonly applied to infants with signs of
      perinatal hypoxia-anoxia. Both hypoxia and hyperoxia have been shown to result in
      apoptosis in the brains of rats in several animal models. One determinant of
      cellular commitment to cell death is the differential expression of the Bcl-2
      family of proteins in response to trauma. Here, we characterize cell death and
      the expression of Bcl-2 homologous proteins in 7-day-old neonatal rat cerebral
      cortex after hypoxia (5% O(2) for 40 min) and/or hyperoxia (>95% O(2) for 2 h
      after hypoxia). The expression of Bcl-2 and Bcl-X(L), two anti-apoptotic
      proteins, decreased at 24 h after hypoxia. Bcl-X(L) increased after either
      hyperoxia or hypoxia+hyperoxia. We did not detect significant changes in the
      cytoplasmic levels of pro-apoptotic protein Bax after any of these three
      treatments. Using cell death ELISA and DNA FragEL assays, we observed increased
      cell death at 24h after hypoxia, hyperoxia or hypoxia+hyperoxia treatments. At 24
      h after either hypoxia, hyperoxia or hypoxia+hyperoxia, caspase 3 activity also
      increased significantly. Our results suggest that both hypoxia and hyperoxia
      alone can induce cell death. The Bcl-2 --> cytochrome c --> caspase 3 pathway
      played a role in hypoxia-induced cell death, while other pathways may be involved
      in hyperoxia-induced cell death.

PMID- 14599485
TI  - Effect of glial cell line-derived neurotrophic factor (GDNF) co-transplantation
      with fetal ventral mesencephalic cells (VMC) on functional restoration in 6
      hydroxydopamine (6-OHDA) lesioned rat model of Parkinson's disease:
      neurobehavioral, neurochemical and immunohistochemical studies.
AB  - Among trophic factors already known, glial cell line-derived neurotrophic factor
      (GDNF) and other members of its family have potent and specific action on
      dopaminergic neurons. In the present investigation an attempt has been made to
      validate the role of GDNF co-transplantation with fetal ventral mesencephalic
      cells (VMC) on functional viability and restoration using neurobehavioral,
      neurochemical and immunohistochemical parameters at 6 weeks post-transplantation
      in 6-hydroxydopamine (6-OHDA) lesioned rat model of Parkinson's disease (PD). A
      significant restoration (P<0.01) in D-amphetamine induced rotations, spontaneous
      and apomorphine induced locomotor activity in rats co-transplanted with VMC and
      GDNF was observed as compared to VMC alone transplanted rats. Level of dopamine
      (DA), 3,4-dihydroxy-phenyl acetic acid (DOPAC) and dopamine D2 (DA-D2) receptors
      in the caudate putamen (CPu) were significantly (P<0.001) restored in co
      transplanted group as compared to VMC transplanted or GDNF administered animals.
      The functional viability of transplanted VMC was confirmed by tyrosine
      hydroxylase (TH) expression and quantification of TH-positive cells by image
      analysis revealed a significant restoration in TH-IR fibers density as well as TH
      IR neurons counts in co-transplanted animals over VMC transplanted animals.
      Results suggest that co-transplantation of VMC and GDNF may be a better approach
      towards functional restoration in 6-OHDA lesioned rat model of Parkinson's
      disease.

PMID- 14599484
TI  - Caffeic acid phenethyl ester blocks apoptosis induced by low potassium in
      cerebellar granule cells.
AB  - Primary cultures of cerebellar granule neurons (CGNs) were prepared from 8-day
      old Wistar rats, and maintained in an appropriate medium containing a high (25
      mM) concentration of KCl. To induce apoptosis, culture medium was replaced with
      serum-free medium (containing 5mM KCl) 8 days after plating. Apoptosis was
      measured by the terminal deoxynucleotidyl transferase-mediated dUTP-fluorescein
      nick end-labeling (TUNEL) method, and by flow cytometry. Since there is evidence
      that an increased formation of reactive oxygen species (ROS) is involved in the
      apoptosis induced by low K(+) (5mM) concentrations, the potential anti-apoptotic
      effect of caffeic acid phenethyl ester (CAPE), a potent flavonoid antioxidant,
      was tested in this experimental model. It was found that CAPE (10 microg/ml)
      promoted cell survival and was capable of blocking the apoptotic process as
      assayed by both TUNEL and flow cytometric methods. The same concentration of CAPE
      prevented the formation of ROS induced by low K(+). Since there is evidence that
      low K(+)-induced apoptosis in CGNs is associated with a drop in intracellular
      Ca(2+) concentration ([Ca(2+)](i)), activation of the cell death effector
      proteases caspase-3 and caspase-9, and of the transcription factor nuclear factor
      kappa B (NF-kappaB), the interference of CAPE with these purported mediators of
      apoptosis was also evaluated. It was found that CAPE did not interfere with the
      marked decrease in [Ca(2+)](i) induced by low K(+), whereas it completely blocked
      caspase-3, caspase-9, and NF-kappaB activation. It is concluded that CAPE could
      exert its anti-apoptotic effect in CGNs by blocking ROS formation and by
      inhibiting caspase activity.

PMID- 14599486
TI  - Hyperthyroidism modifies ecto-nucleotidase activities in synaptosomes from
      hippocampus and cerebral cortex of rats in different phases of development.
AB  - Here we investigate the possible effects of the hyperthyroidism on the hydrolysis
      of the ATP to adenosine in the synaptosomes of hippocampus, cerebral cortex and
      blood serum of rats in different developmental phases. Manifestations of
      hyperthyroidism include anxiety, nervousness, tachycardia, physical hyperactivity
      and weight loss amongst others. The thyroid hormones modulate a number of
      physiological functions in central nervous system, including development,
      function, expression of adenosine A(1) receptors and transport of neuromodulator
      adenosine. Thus, hyperthyroidism was induced in male Wistar rats (5-, 60-, 150-
      and 330-day old) by daily injections of L-thyroxine (T4) for 14 days. Nucleotide
      hydrolysis was decreased by about 14-52% in both hippocampus and cerebral cortex
      in 5 to 60-day-old rats. These changes were also observed in rat blood serum. In
      addition, in 11-month-old rats, inhibition of ADP and AMP hydrolysis persisted in
      the hippocampus, whereas, in cerebral cortex, an increase in AMP hydrolysis was
      detected. Thus, hyperthyroidism affects the extracellular nucleotides balance and
      adenosine production, interfering in neurotransmitter release, development and
      others physiological processes in different systems.

PMID- 14599487
TI  - X-irradiation of adult spinal cord increases its capacity to support neurite
      regeneration in vitro.
AB  - Previous in vitro studies have shown that X-irradiation during early postnatal
      life can change the environment of CNS tissue in later adult life such that it
      becomes more supportive of neurite regeneration from adult dorsal root ganglion
      (DRG) neurons than non-irradiated tissue. The question arises whether or not x
      irradiation during adult life can alter the CNS environment such that it also
      becomes more supportive of neurite regeneration. This was investigated by
      exposing portions of the spinal cord of adult rats to 10, 20 or 40 Gray of X
      irradiation and later using this tissue to prepare cryosections suitable for use
      as a substrate in a cryoculture assay. Fixed cryocultures were immunolabelled
      using anti-glial fibrillary acidic protein (GFAP) to visualise the tissue
      sections and anti-growth associated protein (GAP-43) to visualise the
      regenerating neurites. Tissue sections from sham-irradiated animals and from
      those irradiated with 10 Gray did not support the regeneration of neurites.
      However, sections of spinal cords from rats treated with either 20 or 40 Gray of
      X-irradiation 4 or 32 days prior to sampling were found to support a certain
      degree of neurite regeneration. It is concluded that X-irradiation of adult CNS
      tissue can alter its environment such that it becomes more supportive of neurite
      regeneration and it is speculated that this change may be the result of
      alterations in the glial cell populations in the post-irradiated tissues.

PMID- 14599489
TI  - Juvenile hormone involvement in Drosophila melanogaster male reproduction as
      suggested by the Methoprene-tolerant(27) mutant phenotype.
AB  - Juvenile hormone (JH) involvement in male reproduction is poorly understood. In
      Drosophila melanogaster adults, JH deficiency has been shown to result in lowered
      protein synthesis in male accessory glands. To probe additional roles, we have
      examined males homozygous for a null allele of Methoprene-tolerant (Met). This
      gene is involved in the action of JH, possibly at the JH receptor level, and
      Met(27) null mutants reflect a diminution of JH action. Met(27) males were found
      to have reduced protein accumulation in male accessory glands and to court and
      mate wild-type females much less avidly than do either Met(+) or Met(27); Met(+)
      transgenic males. Exposure of Met(27) males to methoprene partially rescued the
      courtship deficiency. However, sperm transfer as reflected by fertility of
      Met(27) fathers was found to be similar to that of Met(+). Taken together with
      previous work examining the JH-deficient mutant apterous, these results
      corroborate JH involvement in protein synthesis in the male accessory glands and
      suggest a role for JH in promoting male mating behavior in these flies.

PMID- 14599491
TI  - Regulation of prothoracic gland ecdysteroidogenic activity leading to pupal
      metamorphosis.
AB  - The prothoracic glands of early last (fifth) instar larvae of the silkworm are
      inactive with regard to ecdysteroidogenesis and unresponsive to
      prothoracicotropic hormone (PTTH) [J. Insect Physiol. 31 (1985) 455]. In an
      attempt to elucidate the hormonal mechanisms that cause the inactivity, we
      compared the effects of PTTH, dibutyryl cyclic AMP (dbcAMP), a cAMP
      phosphodiesterase inhibitor (IBMX), juvenile hormone analogue (JHA) and 20
      hydroxyecdysone (20E) on secretory activity of the third, fourth and fifth instar
      glands. Among the factors examined, feedback inhibition by 20E was indicated to
      be the most likely factor. Inhibition was moderate in the third and early fourth
      instars while 20E strongly inhibited the glands of middle fourth instar larvae.
      The inhibitory effect of 20E was reduced by removal of the brain and corpora
      allata. Once the glands were suppressed by 20E to the degree of exhibiting
      neither secretory activity nor responsiveness to PTTH, dbcAMP or IBMX did not
      elicit ecdysone secretion at all. Thus the feedback inhibition may shut down
      ecdysteroidogenesis although it is obscure whether it affects the intracellular
      transductory cascade from the PTTH receptor through cAMP. Taken together, this
      evidence suggests that inactivity of the gland in the early fifth instar is
      brought about by feedback inhibition of the glands by 20E occurring in the late
      fourth instar, and that this inactivity is maintained by the juvenile hormone
      found in the early fifth instar.

PMID- 14599490
TI  - Distribution of cuticular protein mRNAs in silk moth integument and imaginal
      discs.
AB  - The distributions of mRNAs for two cuticular proteins of Hyalophora cecropia were
      examined with RT-PCR and in situ hybridization. For major regions of larval and
      pupal cuticle, there was a strong correspondence between the type of cuticle and
      the predominant cuticular protein message found. Epidermal cells underlying soft
      cuticle had mRNA for HCCP12, with a RR-1 consensus attributed to soft cuticle,
      while the epidermal cells associated with hard cuticle had predominantly mRNA for
      HCCP66, a protein with the RR-2 consensus attributed to hard cuticle. Both
      messages were found in all areas of the pupal fore- and hind-wings, with modest
      area-specific difference in concentration being much less than differences in the
      relative abundance of these cuticular proteins.mRNA for HCCP12 was present in
      imaginal discs of feeding larvae of H cecropia. Data from Bombyx mori available
      at SilkBase (http://www.ab.a.u-tokyo.ac.jp/silkbase/) revealed that imaginal
      discs from feeding larvae had abundant mRNA for RR-1 cuticular proteins,
      representing six distinct gene products. Only discs from spinning larvae had
      mRNAs that coded for RR-2 proteins arising from 10 distinct genes. Thus,
      lepidopteran wing imaginal discs can no longer be regarded as inactive in larval
      cuticle production.

PMID- 14599493
TI  - 20E-regulated USP expression and phosphorylation in Drosophila melanogaster.
AB  - The developmental profiles of ultraspiracle protein (USP) in the tissues of
      Drosophila melanogaster were investigated using a USP specific monoclonal
      antibody (mAb) as a probe. Western blot analysis revealed four USP mAb reactive
      bands (p46, p48, p54 and p56), each with tissue- and stage-specific expression
      patterns. The p54 and p56 were expressed in nearly all larval and prepupal
      tissues tested with fluctuations in abundance. However, the p46 and p48 were
      detected exclusively in the midgut of prepupae and shown to be the proteolytic
      products of p54 and p56. A lambda protein phosphatase assay demonstrated that the
      p56 is the phosphorylated form of p54. The expression and phosphorylation of the
      p54 USP is regulated by 20E. Protein kinase consensus recognition sequence
      analysis revealed 10 putative phosphorylation sites in Drosophila USP, with seven
      sites for protein kinase C (PKC) and three sites for casein kinase II (CKII). The
      fact that seven out of 10 putative phosphorylation sites reside in the ligand-
      and DNA-binding domains suggests that phosphorylation may play important role in
      regulating USP function. Identification of the in vivo USP phosphorylation sites
      and signal transduction pathways that regulate the specific USP phosphorylation
      is currently underway.

PMID- 14599492
TI  - Essential roles for the Dhr78 orphan nuclear receptor during molting of the
      Drosophila tracheal system.
AB  - The Drosophila Dhr78 orphan nuclear receptor has been proposed to play a role in
      molting of the tracheal cuticle and regulate gene expression during the third
      larval instar, possibly in response to a novel systemic hormonal signal. Here, we
      show that there are no essential maternal functions for Dhr78 during development,
      and that mutants missing both maternal and zygotic Dhr78 function die primarily
      during second and third instar larval development. We show that defects in the
      tracheal system can be observed as early as the first instar, manifested as
      regions of fluid in the dorsal tracheal trunks. In addition, Dhr78 mutant
      tracheae show a highly penetrant defect in gas filling at the first-to-second
      instar larval molt. Dhr78 expression in only the tracheal system is sufficient to
      rescue the lethality of Dhr78 mutants, and selective inactivation of Dhr78
      function in the tracheae by targeted RNAi is sufficient to result in tracheal
      defects. Finally, we see no evidence for widespread activation of the Dhr78
      ligand binding domain in third instar larvae using the GAL4-LBD system, arguing
      against a systemic hormone for the receptor at this stage in development. Taken
      together, our results indicate that Dhr78 exerts its essential functions during
      molting of the tracheal cuticle in Drosophila.

PMID- 14599494
TI  - Quantity does matter. Juvenile hormone and the onset of vitellogenesis in the
      German cockroach.
AB  - We aimed to elucidate why cockroaches do not produce vitellogenin in immature
      stages, by studying the appearance of vitellogenin mRNA in larvae of Blattella
      germanica. Treatment of female larvae in any of the last three instars with 1
      microg of juvenile hormone (JH) III induces vitellogenin gene transcription,
      which indicates that the fat body is competent to transcribe vitellogenin at
      least from the antepenultimate instar larvae. In untreated females, vitellogenin
      production starts on day 1 after the imaginal molt, when corpora allata begin to
      synthesize JH III at rates doubling the maximal of larval stages. This
      coincidence suggests that the female reaches the threshold of JH production
      necessary to induce vitellogenin synthesis on day 1 of adult life. These data
      lead to postulate that larvae do not synthesize vitellogenin simply because they
      do not produce enough JH, not because their fat body is incompetent.

PMID- 14599495
TI  - The cycling and distribution of PER-like antigen in relation to neurons
      recognized by the antisera to PTTH and EH in Thermobia domestica.
AB  - The cephalic nervous system of the firebrat contains antigens recognized by
      antisera to the clock protein period (PER), the prothoracicotropic hormone (PTTH)
      and the eclosion hormone (EH). The content of the 115 kDa PER-like antigen
      visualized on the western blots fluctuates in diurnal rhythm with a maximum in
      the night. The oscillations entrained in a 12:12 h light/dark (LD) cycle persist
      in the darkness and disappear in continuous light. They are detected by
      immunostaining in 14 pairs of the protocerebral neurons and are extreme in four
      suboesophageal neurons and two cells in each corpus cardiacum that contain PER
      only during the night phase. No circadian fluctuations occur in three lightly
      stained perikarya of the optic lobe. Five cell bodies located in each brain
      hemisphere between the deuto-and the tritocerebrum retain weak immunoreactivity
      under constant illumination. In all cells, the staining is confined to the
      cytoplasm and never occurs in the cell nuclei. The cells containing PER-like
      material do not react with the anti-PTTH and anti-EH antisera, which recognize
      antigens of about 50 and 20 kDa, respectively. The anti-PTTH antiserum stains in
      each brain hemisphere seven neurons in the protocerebrum, eight in the optic
      lobe, and 3-5 in the posterior region of the deutocerebrum. The antiserum to EH
      reacts in each hemisphere with just two cells located medially to the mushroom
      bodies. No cycling of the PTTH-like and EH-like antigens was detected.

PMID- 14599496
TI  - Juvenile hormone potentiates ecdysone receptor-dependent transcription in a
      mammalian cell culture system.
AB  - Insect development is guided by the combined actions of ecdysteroids and juvenile
      hormones (JHs). The transcriptional effects of ecdysteroids are mediated by a
      protein complex consisting of the ecdysone receptor (EcR) and its heterodimeric
      partner, Ultraspiracle (USP), but a corresponding JH receptor has not been
      defined conclusively. Given that the EcR ligand binding domain (LBD) is similar
      to that of the JH-responsive rat farnesoid-X-activated receptor (FXR), we sought
      to define experimental conditions under which EcR-dependent transcription could
      be promoted by JH. Chinese hamster ovary (CHO) cells were transfected with a
      plasmid carrying an ecdysteroid-inducible reporter gene, a second plasmid
      expressing one of the three amino-terminal variants of Drosophila EcR or an EcR
      chimera, and a third plasmid expressing either the mouse retinoid X receptor
      (RXR), or its insect orthologue, USP. Each of the EcR variants responded to the
      synthetic ecdysteroid, muristerone A (murA), but a maximal response to 20
      hydroxyecdysone (20E) was achieved only for specific EcR combinations with its
      heterodimeric partner. Notably, the Drosophila EcR isoforms were responsive to
      20E only when paired with USP, and only EcRB2 activity was further potentiated by
      JHIII in the presence of 20E. EcR chimeras that fuse the activator domains from
      VP16 or the glucocorticoid receptor to the Drosophila EcR DNA-binding and ligand
      binding domains were responsive to ecdysteroids. Again, the effects of JHIII and
      20E were associated with specific partners of the chimeric EcRs. In all
      experiments, the LBD of EcR proved to be the prerequisite component for
      potentiation by JHIII, and in this conformation may resemble the FXR LBD. Our
      results indicate that EcR responsiveness is influenced by the heterodimeric
      partner and that both the N-terminal domain of EcR and the particular ecdysteroid
      affect JHIII potentiation.

PMID- 14599497
TI  - Apolipophorin III: a lipid-triggered molecular switch.
AB  - Apolipophorin III (apoLp-III) is a low molecular weight exchangeable
      apolipoprotein that plays an important role in the enhanced neutral lipid
      transport during insect flight. The protein exists in lipid-free and lipid-bound
      states. The lipid-bound state is the active form of the protein and occurs when
      apoLp-III associates with lipid-enriched lipophorins. ApoLp-III is well
      characterized in two evolutionally divergent species: Locusta migratoria and
      Manduca sexta. The two apolipoproteins interact in a similar manner with model
      phospholipid vesicles, and transform them into discoidal particles. Their low
      intrinsic stability in the lipid-free state likely facilitates interaction with
      lipid surfaces. Low solution pH also favors lipid binding interaction through
      increased exposure of hydrophobic surfaces on apoLp-III. While secondary
      structure is maintained under acidic conditions, apoLp-III tertiary structure is
      altered, adopting molten globule-like characteristics. In studies of apoLp-III
      interaction with natural lipoproteins, we found that apoLp-III is readily
      displaced from the surface of L. migratoria low-density lipophorin by recombinant
      apoLp-III proteins from either L. migratoria or M. sexta. Thus, despite important
      differences between these two apoLp-IIIs (amino acid sequence, presence of
      carbohydrate), their functional similarity is striking. This similarity is also
      illustrated by the recently published NMR solution structure of M. sexta apoLp
      III wherein its molecular architecture closely parallels that of L. migratoria
      apoLp-III.

PMID- 14599498
TI  - Juvenile hormone (JH) esterase: why are you so JH specific?
AB  - Juvenile hormone esterases (JHEs) from six insects belonging to three orders
      (Lepidoptera, Coleoptera, and Diptera) were compared in terms of their deduced
      amino acid sequence and biochemical properties. The four lepidopteran JHEs showed
      from 52% to 59% identity to each other and about 30% identity to the coleopteran
      and dipteran JHEs. The JHE of Manduca sexta was remarkably resistant to the
      addition of organic co-solvents and detergent; in some cases, it demonstrated
      significant activation of activity. Trifluoromethylketone (TFK) inhibitors with
      chain lengths of 8, 10 or 12 carbons were highly effective against both
      lepidopteran and coleopteran JHEs. The coleopteran JHE remained sensitive to TFK
      inhibitors with a chain length of 6 carbons, whereas the lepidopteran JHEs were
      significantly less sensitive. When the chain was altered to a phenethyl moiety,
      the coleopteran JHE remained moderately sensitive, while the lepidopteran JHEs
      were much less sensitive. The lepidopteran and coleopteran JHEs did not show
      dramatic differences in specificity to alpha-naphthyl and rho-nitrophenyl
      substrates. However, as the chain length of the alpha-naphthyl substrates
      increased from propionate to caprylate, there was a trend towards reduced
      activity. The JHE of M. sexta was crystallized and the properties of the crystal
      suggest a high-resolution structure will follow.

PMID- 14599499
TI  - Embryonic expression of juvenile hormone binding protein and its relationship to
      the toxic effects of juvenile hormone in Manduca sexta.
AB  - The juvenile hormones (JHs) regulate a diverse array of insect developmental and
      reproductive processes. One molecular target of JH action is its transporter,
      hemolymph JH binding protein (hJHBP); in the larva of the tobacco hornworm,
      Manduca sexta, low doses of JH can immediately increase hJHBP gene expression.
      Less explored are the effects of JH on embryological development, where early
      hormonal treatment has been shown to affect embryonic development and pupation.
      This study examines the egg form of JHBP and its gene expression during
      embryogenesis of M. sexta, as well as the phenotypic effect JH treatment has on
      embryos and on JHBP gene expression. We here demonstrate that the preponderance
      of JHBP found in the egg is maternally derived and that the embryonic gene and
      protein appear identical to those found in the larva. Expression of the JHBP gene
      begins in both the embryo itself and extra-embryonic tissues 15 h after
      fertilization, long before emergence of a functional fat body and circulatory
      system. Topical application of low JH doses to early embryos resulted in larval
      abnormalities while high doses of the hormone induced embryonic mortality. These
      effects are not mediated through regulation of the JHBP gene, since embryonic
      expression appears invariant in response to JH challenge. The toxicity of JH is
      tightly correlated with the concentration of unbound hormone.

PMID- 14599500
TI  - The ecdysone regulatory cascade and ovarian development in lepidopteran insects:
      insights from the silkmoth paradigm.
AB  - The developing ovariole of the silkmoth Bombyx mori represents an excellent model
      for studies on the changes that occur in gene expression during the execution of
      long-term developmental programs. All stages of follicle development, which
      differ from each other by 2-2.5 h of developmental time, are organized in a
      single array and can be isolated simultaneously for physiological, biochemical
      and gene expression studies from a single animal. Recently, significant progress
      has been made toward the understanding of the hormonal regulation and autonomous
      implementation of the developmental program that governs follicular cell
      differentiation during oogenesis in Bombyx. In this review, the developmental
      career of the ovarian follicle during pharate adult development is discussed in
      view of the new physiological, biochemical and gene expression data that have
      recently accumulated. An overview is presented of the changes in expression of
      structural and regulatory genes and their hormonal regulation in the developing
      follicle during the transitions among the broad developmental periods of
      previtellogenesis, vitellogenesis and choriogenesis. Ovarian development in
      silkmoth pharate adults is induced by 20-hydroxy-ecdysone (20E) through the
      activation of a regulatory cascade similar to the one observed during Drosophila
      development. The transition from previtellogenesis to vitellogenesis corresponds
      to a late response to the hormone and is characterized by the induction of the
      expression of a unique isoform of the nuclear receptor BmHR3 and the follicular
      cell-specific yolk protein ESP. The transition from early to middle and late
      vitellogenesis and choriogenesis, on the other hand, is regulated by positively
      and negatively acting intra- and extra-ovarian factors. In vitro cultures of
      developing ovarioles reveal the requirement for the presence of an as yet
      unidentified growth factor(s) in the hemolymph, while the follicle developmental
      arrest that is observed after treatment with the ecdysone agonist tebufenozide
      indicates the requirement for a decline in the level of 20E. The initiation of
      choriogenesis is characterized by the transcriptional activation of the gene
      BmGATAbeta that encodes GATA transcription factors, and the chorion genes in the
      follicular cells. Furthermore, modulation of the activity of BmGATAbeta at the
      posttranscriptional level is crucial for the stage-specific activation of chorion
      genes during late choriogenesis. The developing ovariole of the silkmoth is,
      therefore, emerging as an important model for the study of insect oogenesis and
      the action of the steroid hormone 20E at the molecular level.

PMID- 14599501
TI  - Methyl palmitate: a novel product of the Medfly (Ceratitis capitata) corpus
      allatum.
AB  - The corpus allatum (CA) of adult female Ceratitis capitata produces methyl
      palmitate (MP) in vitro, in addition to JHB(3) and JH III. Biosynthesized MP
      migrates on TLC and co-elutes from RP-18 HPLC with synthetic MP. Its identity is
      verified herein by GCMS. MP production is up-regulated twofold by mevastatin, an
      inhibitor of mevalonic acid-dependent isoprene biosynthesis. Fosmidomycin, an
      inhibitor of mevalonic acid-independent isoprene synthesis in graminaceous
      plants, up-regulates MP synthesis by about fourfold. However, it does not depress
      JHB(3) biosynthesis concurrently. This suggests that the initial enzyme(s) in the
      conversion of 1-deoxy-xylulose 5-phosphate to isoprene is presumably present in
      C. capitata, but is inhibited by fosmidomycin, and this inhibition diverts
      precursors to MP synthesis. Phytol, an acyclic diterpene, might be suppressing
      isoprene biosynthesis by CA, thereby resulting in a fourfold increase in the MP
      biosynthesis. Linolenic acid is an end-product and its presence in incubation
      media up-regulates MP biosynthesis by twofold, presumably due to the feedback
      diversion to biosynthesis of C(16:0) and its methyl ester. Biosynthesis of MP is
      markedly depressed after mating, while otherwise maintained at significantly
      higher levels in virgin females. MP biosynthesis is significantly reduced in
      virgin females by direct axonal control but is less consistent after mating.

PMID- 14599502
TI  - Activity of the corpora allata of adult female Aedes aegypti: effects of mating
      and feeding.
AB  - The synthesis of juvenile hormone III (JH III) by the isolated corpora allata
      (CA) of Aedes aegypti adult female was studied using an in vitro radiochemical
      assay. We dissected the corpora allata-corpora cardiaca (CA-CC) complex attached
      to a piece of aorta. The complex was left connected to the intact head capsule to
      facilitate the visualization and transfer of the glands. A linear increase in the
      cumulative amount of biosynthesized JH III was found for at least the first 6 h
      of incubation; approximately 45% of the synthesized JH III was present in the
      medium. There was a dependence of JH III synthesis on exogenous methionine
      supply. Using reversed phase high performance liquid chromatography two major
      labeled products biosynthesized by the CA were separated. They co-migrated with
      JH III and methyl farnesoate (MF). The identity of the biosynthesized JH III was
      confirmed by gas chromatography-mass spectrometry. JH III synthesis was only 2.0
      fmol/pair gland/h immediately after adult emergence, but increased to 32.6 fmol/
      pair gland/h 18 h later in sugar-fed females. Two days after emergence, the CA
      biosynthetic activity slowly started to decrease, and reached values of around
      5.3 fmol/pair gland/h by one week after emergence. Synthesis of JH was similar
      from either sugar-fed females mated or unmated. A blood meal resulted in a
      decrease of JH III synthesis in CA from mated females by 12 h after feeding and
      from virgin females by 24 h after feeding. JH III biosynthesis remained low for
      at least 96 h in mated females, but was back to higher levels 72 h after feeding
      in virgin females. Rates of JH III biosynthesis closely reflected the hemolymph
      levels of JH III both after emergence and after a blood meal described by Shapiro
      et al. (1986). The activity of the CA in Aedes aegypti females seems to be
      regulated by developmental changes and nutritional signals, and to be independent
      of mating stimulus.

PMID- 14599503
TI  - PTTH-stimulated ecdysone secretion is dependent upon tyrosine phosphorylation in
      the prothoracic glands of Manduca sexta.
AB  - PTTH stimulates ecdysteroid secretion by the insect prothoracic glands. The
      peptide activates cAMP synthesis in a calcium-dependent manner, ultimately
      enhancing ecdysteroid synthesis. We have found that PTTH stimulates a rapid
      increase in tyrosine phosphorylation of at least four proteins in the prothoracic
      glands of larval Manduca sexta, as seen on Western blots of glandular lysates
      probed with antibody directed against phosphotyrosine. PTTH-stimulated tyrosine
      phosphorylation is blocked by an inhibitor of Src family tyrosine kinases, 4
      amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]-pyrimidine (PP1). The
      inhibitor also blocks PTTH-stimulated ecdysone secretion, as well as PTTH
      stimulated cAMP synthesis. Direct activation of the catalytic subunit of adenylyl
      cyclase by forskolin is not affected by PP1. In addition, ecdysteroid secretion
      stimulated by the cAMP analog dbcAMP is not blocked by PP1. These findings point
      to an important role for a Src-family tyrosine kinase at a very early step in the
      PTTH signaling pathway, prior to the activation of adenylyl cyclase.

PMID- 14599504
TI  - Insights into the molecular basis of the hormonal control of molting and
      metamorphosis from Manduca sexta and Drosophila melanogaster.
AB  - This short review summarizes our current knowledge about the role of
      transcription factors regulated by ecdysteroids and juvenile hormone (JH) in
      larval molting and metamorphosis in the tobacco hornworm, Manduca sexta, and
      Drosophila melanogaster. We show new evidence that EcR-A/USP-2 and E75A
      contribute to the down-regulation of MHR3 after the peak of ecdysteroid. Also,
      there is suggestive evidence that both MHR4 and betaFTZ-F1 may regulate the
      expression of dopa decarboxylase as the ecdysteroid titer declines. We summarize
      the regulation by JH of the Broad transcription factor that normally appears in
      the epidermis in the final larval instar and specifies pupal cuticle formation at
      the metamorphic molt. Premature expression of different Broad isoforms also is
      shown to cause precocious degeneration of the prothoracic glands as well as to
      prevent ecdysteroid release during its presence.

PMID- 14599505
TI  - Metal equilibration in laboratory-contaminated (spiked) sediments used for the
      development of whole-sediment toxicity tests.
AB  - The equilibration and bioavailability of metals in laboratory-contaminated
      sediments have been investigated in order to provide better guidance on
      acceptable procedures for spiking sediments with metals for use in the
      development of whole-sediment toxicity tests. The equilibration rates of Cd, Cu,
      Ni and Zn spiked into three estuarine surface sediments with varying properties
      were investigated. Changes to sediment pH, redox potential, porewater and acid
      soluble metals, acid-volatile sulfide and bacterial activity during
      equilibration, effects of temperature and disturbances following equilibration
      are reported. The addition of metals to sediments caused major decreases in pH
      and increases in redox potential as metals displaced iron(II) into the porewaters
      and added metals and iron (following oxidation) were hydrolyzed. The rates of
      equilibration of metals in porewaters varied considerably and were dependent on
      sediment and metal properties. For the oxic/sub-oxic sediments studied, metal
      spikes of Cd, Cu, Ni and Zn appeared near equilibrium after 25-45, 10-15, 30-70
      and 20-40 days, respectively. Acid-soluble metal concentrations decreased during
      the equilibration period indicating that the metals become more strongly
      associated with the sediments with time (less bioavailable). Bacterial activity
      was greatest in the sediment equilibrated at pH 7 and decreased following the
      addition of metals. During the equilibration period, bacterial activity increased
      in sediments equilibrated at pH 6, remained low in sediments at pH 8 and varied
      erratically in sediments at pH 7. Spiked sediments were shown to equilibrate more
      slowly at lower temperatures resulting in high porewater metal concentrations.
      Disturbances to equilibrated sediments because of sample manipulation caused
      significant iron(II) oxidation and losses of metals from porewaters. The
      importance of documenting spiking and equilibration procedures and carefully
      measuring and reporting sediment parameters is highlighted so that contaminant
      bioavailability and exposure pathways can be interpreted and organism sensitivity
      accurately determined. Recommendations are given for the preparation of metal
      spiked sediments for toxicity testing purposes.

PMID- 14599506
TI  - Effects of acute postnatal exposure to 3,3',4,4'-tetrachlorobiphenyl on sperm
      function and hormone levels in adult rats.
AB  - Polychlorinated biphenyls (PCBs) are considered potential endocrine disruptors
      due to their ability to act as estrogens, antiestrogens and goitrogens. The aim
      of this study is to ascertain whether acute postnatal treatment with 3,3',4,4'
      tetrachlorobiphenyl (CB 77) affects sperm function and hormone levels in adult
      rats. Male Sprague-Dawley rats received CB 77 by ip injection of 2 or 20 mg/kg at
      day 21 and sacrificed at day 112. At day 112, right and left testis weights were
      significantly increased, whereas sperm count, motility, total motile sperm count,
      curvilinear velocity, average path velocity, straight-line velocity, and beat
      cross frequency for motile sperm were significantly decreased in rats treated
      with 20 mg/kg CB 77. Sperm-oocyte penetration rate was significantly reduced in
      rats treated with either 2 or 20 mg/kg CB 77. There was high sperm acrosome
      reaction rate (ARR) in the 20 mg/kg CB 77-treated rats. There was a significant
      increase in thyroid-stimulating hormone level in the 20 mg/kg CB 77 group.
      However, no changes were seen in serum testosterone, thyroid hormones, or
      prolactin concentrations at day 112. In summary, this study showed that postnatal
      exposure to CB 77 might affect spermatogenesis, motility, ARR, and ability of
      fertilizing oocytes in mature rats. These results suggest that the sperm
      functions may be more susceptible or adapt less readily than the thyroid
      functions to endocrine disruption caused by dioxin-like PCB congeners.

PMID- 14599507
TI  - Dose-response relationship in lethal and behavioural effects of different
      insecticides on the parasitic wasp Aphidius ervi.
AB  - Neurotoxic insecticides are widely used for crop protection and behavioural
      perturbations can be expected in surviving beneficial insects, including
      parasitoids of pest insects. The present study aims to investigate the
      relationship between the dose of insecticide parasitoids have been exposed to,
      and the subsequent ability of these parasitoids to respond to host-related cues.
      A four-armed olfactometer, a design widely used to observe orientation responses
      in various insects and parasitoids in particular, was chosen to investigate the
      dose-response relationship. The species studied was Aphidius ervi, a relatively
      generalist parasitoid of aphids, and commercialised for biological control and
      integrated pest management. Active ingredients with similar and different modes
      of action on the nervous system were compared: a pyrethroid (lambda-cyhalothrin),
      an organophosphate (chlorpyrifos), a carbamate (pirimicarb) and a
      carbamyltriazole (triazamate). Adult females were exposed to dry residues on
      glass for 24 h. LD50 were calculated and predicted a high risk of mortality at
      the field application rate. The effect of five increasing residual doses of each
      active ingredient was tested on responses to plant-host odour in the
      olfactometer, from sublethal doses to LD50, and up to LD70 for some products. It
      appeared that none of the doses of lambda-cyhalothrin, chlorpyriphos and
      pirimicarb had any effect on A. ervi responses to the odour from the aphid
      infested plant (Myzus persicae on oilseed rape). But for triazamate, a
      significant dose-behavioural response was quantified and attraction to the odour
      was no longer significant in females surviving the LD50. The possible
      explanations for the presence or absence of effect, depending on the insecticide
      are discussed.

PMID- 14599508
TI  - Toxicity of prednisolone, dexamethasone and their photochemical derivatives on
      aquatic organisms.
AB  - Light exposure of aqueous suspensions of prednisolone and dexamethasone causes
      their partial phototransformation. The photoproducts, isolated by chromatographic
      techniques, have been identified by spectroscopic means. Prednisolone,
      dexamethasone and their photoproducts have been tested to evaluate their acute
      and chronic toxic effects on some freshwater chain organisms. The rotifer
      Brachionus calyciflorus and the crustaceans Thamnocephalus platyurus and Daphnia
      magna were chosen to perform acute toxicity tests, while the alga
      Pseudokircheneriella subcapitata (formerly known as Selenastrum capricornutum)
      and the crustacean Ceriodaphnia dubia to perform chronic tests. The photochemical
      derivatives are more toxic than the parent compounds. Generally low acute
      toxicity was found. Chronic exposure to this class of pharmaceuticals caused
      inhibition of growth population on the freshwater crustacean C. dubia while the
      alga P. subcapitata seems to be less affected by the presence of these drugs.

PMID- 14599509
TI  - A physiologically based assessment of human exposure to radon released from
      groundwater.
AB  - Most of the indoor radon comes directly from the soil beneath the foundation of a
      basement. Recently, radon from groundwater was found to make some contribution to
      the total inhalation risk associated with radon in indoor air. This study
      presents a realistic exposure assessment of a human to indoor radon released from
      groundwater. First, the prediction of indoor radon concentration released from
      groundwater was based on a three-compartment model that was developed to describe
      the transfer and distribution of the radon released from groundwater in a house
      through showers, washing clothes, and flushing toilets. Second, a physiologically
      based pharmacokinetic (PBPK) model for inhaled radon was developed and used to
      estimate tissue group concentrations in a human body. The PBPK model provides
      reasonable predictions of uptake, excretion, and distribution of retained radon
      among tissue groups in the body. Hence, the approach using the PBPK model
      combined with realistic indoor exposure scenarios predicts the radon
      concentrations in tissue groups in the body associated with the indoor radon
      pollution. The results obtained from the study will help increase the
      quantitative understanding of the risk assessment issues associated with the
      indoor radon released from the groundwater.

PMID- 14599510
TI  - Dissipation of alachlor in cotton plant, soil and water and its bioaccumulation
      in fish.
AB  - Dissipation of alachlor in soil and plant in field condition (cotton cropping
      system), and in soil, water and fish in simulated model ecosystem was
      investigated. The acetanilide herbicide, alachlor (50% w/w EC) was applied as pre
      emergence at 2.5 and 5.0 kg a.i.ha(-1) three days after sowing the cotton seeds
      in the field. Soil and plant samples were collected at intervals and analyzed for
      alachlor residues. To study the fate of alachlor in water and fish, a simulated
      model ecosystem was constructed and fish was introduced one day after herbicide
      application. The dissipation of alachlor in water and soil and bioaccumulation in
      fish was observed in model ecosystem. At harvest, cotton lint and seed samples
      were found to contain alachlor well below the detectable level. However, trace
      amounts of residues were found in cotton oil. After harvest of cotton, coriander
      (Coriandrum sativum) and edible amaranth (Amaranthus mangostanus L.) were raised
      for herbicide bioassay. The green leafy vegetable samples did not show any toxic
      symptoms of alachlor residues.

PMID- 14599512
TI  - Preliminary investigation on the environmental occurrence and effects of
      antibiotics used in aquaculture in Italy.
AB  - A preliminary investigation has been carried out on the occurrence and effects of
      antibiotics used in Italian aquaculture with the objective of identifying
      priorities for monitoring programmes. According to the information available on
      the most pertinent and diffuse fish diseases and their related therapies, the
      presence of flumequine and oxytetracycline in sediments sampled from two trout
      farms and three sea-bass farms and in their surrounding environments was selected
      for an analytical investigation. The concentrations of oxytetracycline and
      flumequine varied up to a maximum of 246.3 and 578.8 microg/kg d.w.,
      respectively. Flumequine was seen to have the highest toxicity in a
      bioluminescence assay with EC50 values varying within the range of 12-15 mg/l,
      while the EC50 values for oxytetracycline were within the range of 121-139 mg/l.
      The results of the present study indicate flumequine and oxytetracycline as
      priority chemicals to be monitored for possible environmental side effects of
      aquaculture in Italy. Apart from peak concentrations the chronic presence of
      flumequine and oxytetracycline in sediments both inside and outside farms should
      also be considered. In spite of the potential risks related to the use of
      antibiotics, the concentrations found in the sediments of the studied fish farms
      are significantly lower than those found in other areas.

PMID- 14599511
TI  - A field study of triclosan loss rates in river water (Cibolo Creek, TX).
AB  - Triclosan (TCS) is an anti-microbial agent used in down-the-drain consumer
      products. Following sewage treatment some of the triclosan will enter receiving
      waters. This study was designed to determine the die-away rate of triclosan
      released into a river as part of the sewage treatment plant effluent matrix. The
      study was conducted in Cibolo Creek, a moderate sized stream (discharge
      approximately 0.1 m(3)s(-1)) located in South Central Texas. Triclosan was
      analyzed from samples collected upstream of the sewage treatment plant, the
      sewage treatment plant effluent, and the river downstream from the effluent
      discharge. The first-order loss rate of parent triclosan from the water column
      was calculated from measured data (0.06 h(-1)) and this rate corresponded to a
      76% reduction in triclosan over an 8 km river reach below the discharge.
      Mathematical modeling indicated that sorption and settling accounted for
      approximately 19% of total triclosan loss over 8 km. When removing sorption and
      settling, the remaining amount of triclosan had an estimated first-order loss
      rate of 0.25 h(-1). This loss rate was presumably due to other processes such as
      biodegradation and photolysis. These data show that loss of parent triclosan from
      the water column is rapid. Additional data are needed to fully document loss
      mechanisms.

PMID- 14599514
TI  - Effects of two diluents in the Microtox toxicity bioassay with marine sediments.
AB  - This paper compares the use of two different diluents, EPA synthetic seawater
      (salinity 31 per thousand ) and NaCl standard diluent (salinity 35 per thousand
      ), in the Microtox toxicity bioassay performed on elutriate and solid phase
      derived from marine sediments. The study was performed comparing three series of
      data obtained by the use of the two diluents. In the first series the intensity
      of the natural light output of Vibrio fischeri was considered; in the second
      series pH value, sulphite and ammonia present in the control and in the diluent
      after the treatment with the sediment samples; in the last series, the measured
      toxicity in marine sediments was considered. The light output intensity measured
      with respect to time, gives information about the bacterial activity due to the
      different osmotic conditions. pH values joint with ammonia and sulphite content,
      give information about the effect of the bacterial metabolic activities and of
      the different interaction between each diluent with the sediment sample. At last,
      the comparison of the two diluents on real samples show how the different osmotic
      and hydrogenionic conditions determine different toxicity responses. The results
      show that the EPA diluent allows more suitable environment for the metabolic
      activities of bacteria depending on lower stressing conditions than those present
      when the standard diluent is used. Moreover, the use of EPA diluent reduces the
      risk of false positive response in the execution of the toxicity bioassay.

PMID- 14599513
TI  - Levels of organochlorine compounds in spotted dolphins from the Coiba
      archipelago, Panama.
AB  - Blubber and skin samples from 63 spotted dolphins (Stenella attenuata) (18 males,
      40 females and 5 of unknown sex) were collected by biopsy techniques in the
      waters of the Coiba archipelago. Blubber was analyzed for organochlorine
      compounds and skin for gender determination. Mean levels of HCB
      (hexachlorobenzene), tPCB (polychlorinated biphenyls) and tDDT
      (dichlorodiphenyltrichloroethane) were 0.064, 2.30 and 6.4 mgkg(-1),
      respectively. These levels are low and are not considered to represent a threat
      to the S. attenuata population. No significant differences either in
      concentrations of HCB, tPCB and tDDT or in PCB profiles were observed between
      males and females. The ratio tDDT/tPCB was 2.69, indicating predominantly
      agrarian versus industrial activities in the area. The ratio ppDDE/tDDT was 0.83,
      a high figure that suggests both a local reduction of DDT inputs and a high rate
      of DDT degradation. Significant quantitative and qualitative differences were
      observed between two schools, suggesting intra-population heterogeneity in
      organochlorine exposure possibly due to demographic segregation.

PMID- 14599515
TI  - Why are grape/fresh wine anthocyanins so simple and why is it that red wine color
      lasts so long?
AB  - Vitis vinifera red berries are characterized by anthocyanins whose chemical
      structures are among the simplest encountered in higher plants. On the contrary,
      many plants, including orchids, petunias, red cabbage, elderberries, potatoes for
      instance, have developed very complicated anthocyanins featuring side-chains at
      the available positions of the aglycone skeleton. Such pigments were shown to
      possess bio-physico-chemical properties not to be seen with the grape common
      anthocyanins. Among beverages (water, tea, beer, wine, coffee, juices, milk), red
      wine is the only one whose organoleptic properties improve with time and this is
      called ageing. The grape/fresh red wine pigments, after a few months, disappear
      from the wine giving birth to new pigments resulting from the wine spontaneous
      chemistry allowing it to remain red for many years. What are the wine pigments
      and why are they so stable is the purpose of this mini-review. The structural
      simplicity of grape anthocyanins and the long lasting colour of red wine is
      another French paradox; we call it French paradox II.

PMID- 14599516
TI  - Antifreeze proteins in higher plants.
AB  - Overwintering plants produce antifreeze proteins (AFPs) having the ability to
      adsorb onto the surface of ice crystals and modify their growth. Recently,
      several AFPs have been isolated and characterized and five full-length AFP cDNAs
      have been cloned and characterized in higher plants. The derived amino acid
      sequences have shown low homology for identical residues. Theoretical and
      experimental models for structure of Lolium perenne AFP have been proposed. In
      addition, it was found that the hormone ethylene is involved in regulating
      antifreeze activity in response to cold. In this review, it is seen that the
      physiological and biochemical roles of AFPs may be important to protect the plant
      tissues from mechanical stress caused by ice formation.

PMID- 14599517
TI  - Ellagitannin biosynthesis: laccase-catalyzed dimerization of tellimagrandin II to
      cornusiin E in Tellima grandiflora.
AB  - An enzyme has been purified from leaves of the weed Tellima grandiflora (fringe
      cups, Saxifragaceae) that catalyzed the O2-dependent oxidation of the monomeric
      ellagitannin, tellimagrandin II, to a dimeric derivative, cornusiin E. The
      apparently homogeneous enzyme preparation had a Mr of ca. 160,000 (with four
      subunits of Mr 40,000), a pH-optimum and an isoelectric point at pH 5.2, and was
      most stable at pH 4.3. Inhibition studies revealed that this new enzyme, for
      which the systematic name 'tellimagrandin II: O2 oxidoreductase' is proposed, is
      a member of the laccase (EC 1.10.3.2) family of phenol oxidases. The properties
      of this enzyme differed from that of a related laccase that catalyzed the
      transition of 1,2,3,4,6-pentagalloylglucopyranose to tellimagrandin II, the
      preceding step in the biosynthetic route to cornusin E.

PMID- 14599519
TI  - Expression of plastid-encoded photosynthetic genes during chloroplast or
      chromoplast differentiation in Cucurbitae pepo L. fruits.
AB  - The objective of the study was to determine the patterns of expression of two
      photosynthetic genes rbcL and psbA, during chloroplast and chromoplast
      differentiation in fruit tissues of three Cucurbitae pepo L. cultivars: Early
      Prolific, Foodhook Zucchini and Bicolor Gourds. In two Early Prolific isogenic
      lines, YYBB and YYB+B+, the steady-state amounts of rbcL and psbA transcripts
      increased with fruit development upto 14 days post-pollination. The YYB+B+ line
      in which chloroplast differentiates into chromoplast at about pollination, did
      not show significantly higher amounts of both transcripts compared to YYBB, in
      which chromoplast develops early prior to pollination. In the Bicolor Gourds, in
      which the chromoplast and chloroplast containing tissues lie in juxtaposition on
      the same fruit, showed little differences in rbcL and psbA transcripts between
      the two tissues, if any the chromoplast containing tissue contained more of both
      transcripts than the chloroplast containing tissue. In Fordhook Zucchini fruits,
      where the chloroplast containing tissue developed early prior to pollination and
      was maintained, the steady-state amounts of rbcL transcripts increased to a
      maximum at 3 days post-pollination and levelled at 14 and 21 days post
      pollination. In contrast, in Fordhook Zucchini fruits, the psbA transcript
      increased gradually up to 21 days post-pollination. In Fordhook Zucchini, the
      apparent ratios of psbA transcripts versus rbcL transcripts ranged from 2.5 to
      3.9, at day 3 to 21 post-pollination, while in Bicolor Gourds were 2.9 and 4.5 at
      days 14 and 21 post-pollination. The two photosynthetic genes, psbA and rbcL were
      developmentally regulated and differentially expressed. However, their expression
      in chloroplast containing fruit tissues was not higher than in the chromoplast
      containing fruit tissues.

PMID- 14599518
TI  - Molecular evaluation of a spearmint mutant altered in the expression of limonene
      hydroxylases that direct essential oil monoterpene biosynthesis.
AB  - Gamma irradiation of Scotch spearmint created a mutant line, 643-10-74, which has
      an altered essential oil reminiscent of peppermint because the monoterpene
      metabolites in the oil glands of the mutant are predominantly oxygenated at the
      C3 position of the p-menthane ring instead of the C6 position normally found in
      spearmint. The limonene hydroxylase genes responsible for directing the
      regiochemistry of oxygenation were cloned from Scotch spearmint and mutant 643
      and expressed in Escherichia coli. The limonene bydroxylase from the wild-type
      parent hydroxylated the C6 position while the enzyme from the mutant oxygenated
      the C3 position. Comparison of the amino acid sequences with other limonene
      hydroxylases showed that the mutant enzyme was more closely related to the
      peppermint limonene-3-hydroxylases than to the spearmint limonene-6-hydroxylases.
      Because of the sequence differences between the Scotch spearmint and mutant 643
      limonene hydroxylases, it is most likely that the mutation did not occur within
      the structural gene for limonene hydroxylase but rather at a regulatory site
      within the genome that controls the expression of one or the other regiospecific
      variants.

PMID- 14599520
TI  - Pyrrolizidine alkaloids in and on the leaf surface of Senecio jacobaea L.
AB  - This is the first study showing that alkaloids are present on the leaf surface of
      plants. A concentration of 30-230 pmol/cm2 pyrrolizidine alkaloids (PA's) was
      detected in 8 different samples taken from Senecio jacobaea. PA concentration on
      the leaves was marginally correlated with PA concentration of the total leaf
      tissues. The PA spectrum on the leaf differed from the PA spectrum of the total
      leaf.

PMID- 14599521
TI  - LC-NMR and LC-MS analysis of 2,3,10,11-oxygenated protoberberine metabolites in
      Corydalis cell cultures.
AB  - The metabolism of 2,3,10,11-oxygenated protoberberine alkaloids was studied in
      cell cultures of Corydalis species. Without prior isolation, the structures of
      the metabolites were determined by LC-MS and LC-NMR analyses.
      Tetrahydropseudocoptisine alpha-N-metho salt, pseudoprotopine, and pseudomuramine
      were identified for the first time, and preliminary evidence for metabolic
      pathways to the formation of these alkaloids were obtained.

PMID- 14599522
TI  - Enhancing phytoremediative ability of Pisum sativum by EDTA application.
AB  - The aim of our research was to demonstrate how the presence of EDTA affects
      resistance of pea plants to Pb and Pb-EDTA presence, and to show the effectivity
      of lead ions accumulation and translocation. It was determined that EDTA not only
      increased the amount of Pb taken up by plants but also Pb ion transport through
      the xylem and metal translocation from roots to stems and leaves. It can be seen
      in the presented research results that addition of the chelator with Pb limited
      metal phytotoxicity. We also demonstrated a significant effect of EDTA not only
      on Pb accumulation and metal transport to the aboveground parts but also on the
      profile and amount of thiol compounds: glutathione (GSH), homoglutathione (hGSH)
      or phytochelatins (PCs), synthesized by the plants. We observed a significant
      effect of the synthetic chelator on increasing the level of Pb accumulation in
      roots of plants treated with Pb including EDTA (0.5 and 1 mM). Pisum sativum
      plants treated only with 1 mM Pb(NO3)2 accumulated over 50 mg Pb x g(-1) dry wt
      during 4 days of cultivation. Whereas in roots of pea plants exposed to Pb+0.5 mM
      EDTA 35% more Pb was observed. When 1 mM EDTA was applied roots of pea
      accumulated over 67% more metal. The presence of EDTA also increased metal uptake
      and transport to the aboveground parts. In pea plants treated only with 1 mM lead
      nitrate less than 3 mg Pb x g(-1) dry wt was transported, whereas in P. sativum
      treated with Pb-EDTA doubled amount of Pb was observed in stems and leaves.

PMID- 14599523
TI  - Synthesis and anti-herpes simplex viral activity of monoglycosyl diglycerides.
AB  - Based on the discovery of antiviral beta-galactosyl diglycerides from
      Clinacanthus nutans leaves, 19 monoglycosyl diglycerides were synthesized and
      examined for inhibitory effect on herpes simplex virus types 1 and 2 (HSV-1, HSV
      2). A study of the structure-activity relationships of the synthetic monoglycosyl
      diglycerides indicated that the fatty acyl moieties were critical for inhibitory
      action with higher activity displayed as the acyl groups became more olefinic in
      character. The sugar moiety was also important for anti-HSV action; however, the
      type of sugar (glucose or galactose) did not affect activity. The stereochemistry
      at C-2 of the glycerol backbone displayed no significant effect on anti-HSV
      activity. Among the compounds synthesized, 1,2-O-dilinolenoyl-3-O-beta-D
      glucopyranosyl-sn-glycerol showed the highest inhibitory activity against HSV-1
      and HSV-2 with IC50 values of 12.5+/-0.5 and 18.5+/-1.5 microg/ml, respectively.

PMID- 14599524
TI  - Isoflavonoids from Dalbergia olivari.
AB  - Two isoflavonoids, named olibergin A (1) and B (2) were isolated from the stem
      bark of Dalbergia oliveri (Leguminosae). Along with three previously known
      compounds, they are inhibitors of Epstein-Barr virus early antigen activation
      induced by 12-O-tetradecanoylphorbol-13-acetate in Raji cells. Their structures
      were elucidated on the basis of spectroscopic analyses.

PMID- 14599525
TI  - Composition and anti-plasmodial activities of essential oils from some
      Cameroonian medicinal plants.
AB  - In a search for new plant-derived biologically active compounds against malaria
      parasites, five essential oils extracted from the Cameroonian plants Xylopia
      phloiodora, Pachypodanthium confine, Antidesma laciniatum, Xylopia aethiopica,
      and Hexalobus crispiflorus were evaluated in regard to their anti-plasmodial
      activity against the W2 strain of Plasmodium falciparum. The oils were obtained
      from the plants with 0.12, 0.13, 0.18, 0.6 and 0.1% yields (relatively to dried
      material weight) respectively. Analysis by gas chromatography and mass
      spectrometry identified mainly terpenoids, among which alpha-copaene, gamma
      cadinene, delta-cadinene, alpha-cadinol, spathulenol and caryophyllene oxide were
      most commonly found. The five oils were active against Plasmodium falciparum in
      culture. The most effective was the oil of Hexalobus crispiflorus, with an IC50
      of 2 microg/ml.

PMID- 14599527
TI  - 2-Hydroxyflavanones from Leptospermum polygalifolium subsp. polygalifolium
      Equilibrating sets of hemiacetal isomers.
AB  - 2,5-Dihydroxy-6-methyl-7-methoxyflavanone and its isomer 2,5-dihydroxy-8-methyl-7
      methoxyflavanone have been identified as the principal components in the ethanol
      extract of L. polygalifolium subsp. polygalifolium. The former compound has been
      separated from the latter for the first time by crystallisation. Other flavonoids
      identified include an equilibrating mixture of novel 2,3,5-trihydroxyflavanones;
      the first discovery of this type of compound from a natural source. This study
      has also confirmed the presence of the triketones, flavesone and leptospermone,
      along with the closely related isoleptospermone as anti-microbial components.

PMID- 14599526
TI  - Antioxidant flavonoids from the rhizomes of Helminthostachys zeylanica.
AB  - Eight flavonoids, ugonins E-L (1-8), were isolated from the rhizomes of
      Helminthostachys zeylanica, and their structures were established on the basis of
      spectral evidence. Compounds 3-8 were evaluated for their antioxidative activity
      in the 1, 1-diphenyl-2-picrylhydrazyl (DPPH) assay. Compounds 6, 7 and 8 were
      more active than Trolox, with IC20 values of 5.29 +/- 0.32, 7.23 +/- 0.22, and
      7.93 +/- 0.31, respectively.

PMID- 14599528
TI  - Acylated flavone glycosides from Veronica.
AB  - A survey of the flavonoid glycosides of selected taxa in the genus Veronica
      yielded two new acylated 5,6,7,3',4'-pentahydroxyflavone (6-hydroxyluteolin)
      glycosides and two unusual allose-containing acylated 5,7,8,4'
      tetrahydroxyflavone (isoscutellarein) glycosides. The new compounds were isolated
      from V. liwanensis and V. longifolia and identified using NMR spectroscopy as 6
      hydroxyluteolin 4'-methyl ether 7-O-alpha-rhamnopyranosyl(1"'-->2")[6"-O-acetyl
      beta-glucopyranoside] and 6-hydroxyluteolin 7-O-(6"-O-(E)-caffeoyl)-beta
      glucopyranoside, respectively. Isoscutellarein 7-O-(6"'-O-acetyl)-beta
      allopyranosyl(1"'-->2")-beta-glucopyranoside was obtained from both V.
      intercedens and V. orientalis and its 4'-methyl ether from V. orientalis only.
      Complete 1H and 13C NMR spectral assignments are presented for both
      isoscutellarein glycosides. Two iridoid glucosides new to the genus Veronica
      (melittoside and globularifolin) were also isolated from V. intercedens.

PMID- 14599529
TI  - Alpha-pyrones and a 2(5H)-furanone from Hyptis pectinata.
AB  - Three pyrones and a 2(5H)-furanone, designated pectinolides D-G, have been
      isolated from the dichloromethane extract of Hyptis pectinata. The metabolites
      were characterized on the basis of 1D and 2D NMR spectroscopic techniques. The
      pyrones were identified as 6S-[3S,6S-(diacetoxy)-5R-hydroxy-1Z-heptenyl]-5S
      hydroxy-5,6-dihydro-2H-pyran-2-one (1)- pectinolide D, 6S-[3S,5R,6S-(triacetoxy)
      1Z-heptenyl]-5S-acetoxy-5,6-dihydro-2H-pyran-2-one (2)- pectinolide E and 6S
      [3S,5R,6S-(triacetoxy)-1Z-heptenyl]-5S-acetoxy-4R-methoxy-3,4,5,6-tetrahydro-4H
      pyran-2-one (3)- pectinolide F. The furanone was identified as [2'Z,5(1')Z] 5
      (4'S,6'R,7'S-triacetoxy-2-octenylidene)-2(5H)-furanone (4)-pectinolide G.

PMID- 14599530
TI  - ent-Labdane diterpenes from the aquatic plant Potamogeton pectinatus.
AB  - Four new ent-labdane diterpenes were isolated from the freshwater aquatic plant
      Potamogeton pectinatus, together with two known furano-ent-labdanes. The new
      compounds were assigned the structures methyl-15,16-epoxy-12(R)-acetoxy- 8(17),
      13(16),14-ent-labdatrien-19-oate,15,16-epoxy-12(R)-acetoxy-8(17), 13(16),14-ent
      labdatrien-19-oic acid, 8(17),13-ent-labdadien-15 --> 16-lactone-19-oic acid and
      16-hydroxy-8(17),13-ent-labdadien-15,16-olid-19-oic acid by spectroscopic means.
      Some of these labdanes showed a strong algicidal activity against Raphidocelis
      subcapitata.

PMID- 14599532
TI  - Fast functional brain signal changes detected by diffusion weighted fMRI.
AB  - Functional magnetic resonance imaging (fMRI) has become the method of choice in
      the study of system neuroscience, as evidenced by an explosion of such literature
      in the past decade. Contrast mechanisms based on the blood oxygenation level,
      volume, and flow changes have been used to non-invasively detect brain activation
      secondary to the neuronal activity. However, because of the hemodynamic
      modulations inherent in these signals, their spatial and temporal characteristics
      are influenced by the complex geometry and varying delivery speed of the brain
      vasculature. Consequently, spatial dispersions and temporal delays are commonly
      seen in the brain activity using fMRI. It is thus of critical importance to
      investigate alternative contrast mechanisms that may offer shorter temporal
      delays and more direct spatial localization. In light of a recent phantom study
      which demonstrated the possibility to detect the destructive phase addition from
      the spatially incoherent, yet temporally synchronized, displacements caused by
      the Lorentz force experienced during electrical conduction within a strong
      magnetic field, we seek to apply similar imaging technique to investigate the
      functional signal changes that may provide alternative temporal and spatial
      characteristics. It is found that by using heavy diffusion weighting, which is
      one form of displacement encoding strategies, to remove the vascular signal and
      sensitize the minute and incoherent displacement, one can detect fast dynamic
      signal changes synchronized to the task. This finding may help take an initial
      step toward direct non-invasive MRI detection of the neuronal activity with
      improved temporal accuracy.

PMID- 14599533
TI  - A signal subspace approach for modeling the hemodynamic response function in
      fMRI.
AB  - Many fMRI analysis methods use a model for the hemodynamic response function
      (HRF). Common models of the HRF, such as the Gaussian or Gamma functions, have
      parameters that are usually selected a priori by the data analyst. A new method
      is presented that characterizes the HRF over a wide range of parameters via three
      basis signals derived using principal component analysis (PCA). Covering the HRF
      variability, these three basis signals together with the stimulation pattern
      define signal subspaces which are applicable to both linear and nonlinear
      modeling and identification of the HRF and for various activation detection
      strategies. Analysis of simulated fMRI data using the proposed signal subspace
      showed increased detection sensitivity compared to the case of using a previously
      proposed trigonometric subspace. The methodology was also applied to activation
      detection in both event-related and block design experimental fMRI data using
      both linear and nonlinear modeling of the HRF. The activated regions were
      consistent with previous studies, indicating the ability of the proposed approach
      in detecting brain activation without a priori assumptions about the shape
      parameters of the HRF. The utility of the proposed basis functions in identifying
      the HRF is demonstrated by estimating the HRF in different activated regions.

PMID- 14599534
TI  - Reduced capillary perfusion and permeability in human tumour xenografts treated
      with the VEGF signalling inhibitor ZD4190: an in vivo assessment using dynamic MR
      imaging and macromolecular contrast media.
AB  - We describe the use of perfusion-permeability magnetic resonance imaging (ppMRI)
      to study hemodynamic parameters in human prostate tumor xenografts, following
      treatment with the vascular endothelial growth factor-A (VEGF) receptor tyrosine
      kinase inhibitor, ZD4190. Using a macromolecular contrast agent (P792), a fast MR
      imaging protocol and a compartmental data analysis, we were able to demonstrate a
      significant simultaneous reduction in tumor vascular permeability, tumor vascular
      volume and tumor blood flow (43%, 30% and 42%, respectively) following ZD4190
      treatment (100 mg/kg orally, 24 h and 2 h prior to imaging). This study indicates
      that MR imaging can be used to measure multiple hemodynamic parameters in tumors,
      and that tumor vascular permeability, volume and flow, can change in response to
      acute treatment with a VEGF signaling inhibitor.

PMID- 14599535
TI  - Comparison of MRI with EMG to study muscle activity associated with dynamic
      plantar flexion.
AB  - This study compared magnetic resonance imaging (MRI) and surface electromyography
      (EMG) to evaluate the effect of knee angle upon plantar flexion activity in the
      triceps surae muscles [medial & lateral gastrocnemius (MG, LG) and the soleus
      (SOL)]. Two weight & height matched groups performed identical protocols, twelve
      (6M, 6F) in the MRI group, twelve (8M, 4F) in the EMG group. Subjects plantar
      flexed dynamically for 2 min at 25% of 1-repetition maximum voluntary contraction
      (1-RM). Exercise was performed with the knee extended (0 degrees flexion), flexed
      (90 degrees ), and partially flexed (45 degrees ). In the MRI group spin-echo
      images were acquired before and immediately following each exercise session. T(2)
      times, calculated at rest and after exercise by fitting the echoes to a
      monoexponential decay pattern with a least-squares algorithm, were compared with
      EMG data. In the EMG group a bipolar electrode was used to collect samples were
      from the MG, LG, SOL, and anterior tibialis (TA) during exercise at each knee
      angle, MRI also examined the peroneus (PER). At 0 degrees flexion MRI
      demonstrated a significant post-exercise T(2) increase in the MG (p < or =
      0.001), LG (p < or = 0.001), and PER (p < or = 0.01), with no T(2) change in the
      SOL or TA. At 90 degrees flexion there was a significant T(2) increase in the SOL
      (p < or = 0.001) with no significant T(2) change in the MG, LG, PER, or TA. At 45
      degrees T(2) increased significantly in the SOL (p < or = 0.001) and LG (p < or =
      0.05), but not the MG, PER, or TA. EMG produced similar results with the
      exception that there was significant activity in the TA during the relaxation
      cycle of the 90 degrees protocol. We conclude that: 1) Soleus activity is
      measurable by MRI; and 2) MRI and EMG produce similar results from different
      physiological sources, and are therefore complementary tools for evaluating
      muscle activity.

PMID- 14599537
TI  - Liver metastases from unknown primary site: demonstration on MR images.
AB  - To demonstrate the MR imaging features of liver metastases in patients with the
      clinical and histologic diagnosis of tumors of unknown primary tumors, a
      retrospective 7-year study was performed that included a total of 14 consecutive
      patients (7 men and 7 women; age range, 39-82 years; mean age, 60.6 years) with
      liver metastases from unknown primary site who had undergone MR imaging. The
      following lesion features were evaluated: a) number, b) diameter, c) signal
      intensity on T1 and T(2)-weighted images, and d) pattern of enhancement on
      immediate, 45 s and 90 s post gadolinium images. Lesions were classified as
      hypovascular, hypervascular and nearly isovascular relative to liver parenchyma
      as shown on immediate post gadolinium images. Patients were separated into four
      major groups, related to the histologic diagnosis of the lesions: (I) poorly
      differentiated neoplasms; (II) well-differentiated and moderately differentiated
      adenocarcinoma; (III) squamous cell carcinoma; (IV) combined poorly
      differentiated carcinoma and poorly differentiated adenocarcinoma. MRI findings
      were correlated with histologic information obtained by chart review and
      confirmed by retrospective histopathology review. All patients had the histologic
      diagnosis of adenocarcinoma: 8 patients belonged to group II (1 patient with the
      subtype well-differentiated and 7 patients with the subtype moderately
      differentiated) and 6 patients to group IV. Eleven patients (79%) presented with
      multiple lesions distributed throughout both hepatic lobes; 3 patients exhibited
      solitary lesions. All solitary metastases possessed a diameter equal or larger
      than 5 cm. Patients with multiple metastases demonstrated a wide range of
      diameter, ranging from less than 1.5 cm to more than 5 cm. Regarding lesion
      vascularity, 4 of 13 of the patients had hypovascular metastases and 9 of 13 of
      the patients had hypervascular lesions. One patient demonstrated both types of
      lesions. Five of six patients with the histopathologic diagnosis of poorly
      differentiated adenocarcinoma demonstrated hypervascular metastases. Solitary
      metastases were most often hypovascular (2 of 3); however no correlation with the
      histologic subtype was possible. Liver metastases from unknown primary site are
      often multiple and often hypervascular. Poorly differentiated tumors are the most
      common histologic type. Metastases are not uncommonly hypovascular, and these are
      often solitary.

PMID- 14599536
TI  - Generalized Kohonen's competitive learning algorithms for ophthalmological MR
      image segmentation.
AB  - Kohonen's self-organizing map is a two-layer feedforward competitive learning
      network. It has been used as a competitive learning clustering algorithm. In this
      paper, we generalize Kohonen's competitive learning (KCL) algorithm with fuzzy
      and fuzzy-soft types called fuzzy KCL (FKCL) and fuzzy-soft KCL (FSKCL). These
      generalized KCL algorithms fuse the competitive learning with soft competition
      and fuzzy c-means (FCM) membership functions. We then apply these generalized
      KCLs to MRI and MRA ophthalmological segmentations. These KCL-based MRI
      segmentation techniques are useful in reducing medical image noise effects using
      a learning mechanism. They may be particularly helpful in clinical diagnosis. Two
      real cases with MR image data recommended by an ophthalmologist are examined.
      First case is a patient with Retinoblastoma in her left eye, an inborn malignant
      neoplasm of the retina frequently metastasis beyond the lacrimal cribrosa. The
      second case is a patient with complete left side oculomotor palsy immediately
      after a motor vehicle accident. Her brain MRI with MRA, skull routine, orbital
      CT, and cerebral angiography did not reveal brainstem lesions, skull fractures,
      or vascular anomalies. These generalized KCL algorithms were used in segmenting
      the ophthalmological MRIs. KCL, FKCL and FSKCL comparisons are made. Overall, the
      FSKCL algorithm is recommended for use in MR image segmentation as an aid to
      small lesion diagnosis.

PMID- 14599538
TI  - Correlative high-resolution MR-anatomic study of sciatic, ulnar, and proper
      palmar digital nerve.
AB  - Aim of this study was o evaluate the effectiveness of high-resolution MR imaging
      in demonstrating the anatomic structure of peripheral nerves of different
      diameter and composition. The dissected sciatic, ulnar, and proper palmar digital
      nerve of fresh cadavers were imaged at pre-selected landmarks on a 3T MR scanner.
      The nerves were then embedded in formalin, sliced, stained, and microscopically
      analyzed. The size, shape, and signal intensity of the sheath and axonal
      structures in the nerves at the landmarks were identified in MR images by
      comparison with histologic sections. The fascicles were clearly distinguished and
      counted in all specimens with MR imaging and showed only small differences from
      the histologic evaluation. High resolution MR imaging has the potential to
      visualize the fascicular structure in nerves of all sizes, which may be helpful
      in the preoperative assessment.

PMID- 14599539
TI  - Magnetic resonance imaging of intraductal papilloma of the breast.
AB  - To describe the appearance of isolated intraductal papilloma on contrast-enhanced
      water-specific, high spatial-resolution and rapid dynamic breast MRI, a
      retrospective review of unilateral breast images of 15 pathologically proven
      papilloma was performed. MRI revealed three patterns: Four papillomas were small,
      smooth, enhancing masses at the posterior end of an enlarged duct, corresponding
      to the "small lumenal mass" appearance of papilloma known from galactography. MRI
      detected two of these "small lumenal mass" papillomas in patients with abnormal
      nipple discharge even when galactography was unsuccessful. Seven papillomas were
      irregular enhancing masses detected in patients without nipple discharge. None of
      these papillomas had specifically benign findings. All seven demonstrated rapid
      enhancement and three showed rim enhancement or spiculation. These "tumor-like"
      papillomas mimicked invasive breast cancer on MRI. Four papillomas were occult on
      MRI, not revealed by either contrast-enhanced MRI or fat-suppressed T(2)-weighted
      MRI. Intraductal papillomas present with a variable appearance on MRI ranging
      from occult to "small lumenal mass" papillomas to irregular rapidly enhancing
      lesions that cannot be distinguished from invasive cancers.

PMID- 14599540
TI  - Magnetization transfer and T2 quantitation in normal appearing cortical gray
      matter and white matter adjacent to focal abnormality in patients with traumatic
      brain injury.
AB  - Traumatic brain injury (TBI) is one of the commonest causes of morbidity and
      mortality in the developed countries with posttraumatic epilepsy and functional
      disability being its major sequelae. The purpose of this study was to test the
      hypothesis whether the normal appearing adjacent gray and white matter regions on
      T2 and T1 weighted magnetization transfer (MT) weighted images show any
      abnormality on quantitative imaging in patients with TBI. A total of 51 patients
      with TBI and 10 normal subjects were included in this study. There were
      significant differences in T2 and MT ratio values of T2 weighted and T1 weighted
      MT normal appearing gray matter regions adjacent to focal image abnormality
      compared to normal gray matter regions in the normal individuals as corresponding
      contralateral regions of the TBI patient's group (p < 0.05). However the
      adjoining normal appearing white matter quantitative values did not show any
      significant change compared to the corresponding contralateral normal white
      matter values. We conclude that quantitative T2 and MT ratio values provide
      additional abnormality in patients with TBI that is not discernable on
      conventional T2 weighted and T1 weighted MT imaging especially in gray matter.
      This additional information may be of value in overall management of these
      patients with TBI.

PMID- 14599541
TI  - Computer-assisted enhanced volumetric segmentation magnetic resonance imaging
      data using a mixture of artificial neural networks.
AB  - An accurate computer-assisted method able to perform regional segmentation on 3D
      single modality images and measure its volume is designed using a mixture of
      unsupervised and supervised artificial neural networks. Firstly, an unsupervised
      artificial neural network is used to estimate representative textures that appear
      in the images. The region of interest of the resultant images is selected by
      means of a multi-layer perceptron after a training using a single sample slice,
      which contains a central portion of the 3D region of interest. The method was
      applied to magnetic resonance imaging data collected from an experimental acute
      inflammatory model (T(2) weighted) and from a clinical study of human Alzheimer's
      disease (T(1) weighted) to evaluate the proposed method. In the first case, a
      high correlation and parallelism was registered between the volumetric
      measurements, of the injured and healthy tissue, by the proposed method with
      respect to the manual measurements (r = 0.82 and p < 0.05) and to the
      histopathological studies (r = 0.87 and p < 0.05). The method was also applied to
      the clinical studies, and similar results were derived of the manual and semi
      automatic volumetric measurement of both hippocampus and the corpus callosum
      (0.95 and 0.88).

PMID- 14599542
TI  - Superiority of 3D wavelet-packet denoising in MR microscopy.
AB  - Three dimensional Magnetic Resonance Imaging (MRI) datasets are becoming
      increasingly important in clinical and research applications because of their
      inherent signal to noise (SNR) advantages, high resolution and isotropic voxels.
      Despite SNR advantages, some 3D acquisitions may be SNR-limited, particularly in
      MR microscopy. Historically, both classic filtering and wavelet-based denoising
      techniques have been performed on a slice-by-slice basis. In principle, adaptive
      techniques such as best- basis wavelet-packet denoising might offer inherent
      advantages when performed in 3D, instead of 2D, by tracking through plane
      "structure" and suppressing noise "pseudostructure." This hypothesis was tested
      in 10 volumetric MR microscopy datasets from several different MR microscopy
      atlas projects. 3D wavelet-packet denoised images consistently yielded lower
      minimum mean-square error and subjectively perceived noise power than
      corresponding 2D denoised images using otherwise identical algorithms and
      parameters. MR microscopy researchers preferred the denoised images to the
      unprocessed images for their atlas projects.

PMID- 14599543
TI  - Metabolite ratios to assumed stable creatine level may confound the
      quantification of proton brain MR spectroscopy.
AB  - In localized brain proton MR spectroscopy ((1)H-MRS), metabolites' levels are
      often expressed as ratios, rather than as absolute concentrations. Frequently,
      their denominator is the creatine [Cr], which level is explicitly assumed to be
      stable in normal as well as in many pathologic states. The rationale is that
      ratios self-correct for imager and localization method differences, gain
      instabilities, regional susceptibility variations and partial volume effects. The
      implicit assumption is that these benefits are worth their cost(w)-(w)
      propagation of the individual variation of each of the ratio's components. To
      test this hypothesis, absolute levels of N-acetylaspartate [NAA], choline [Cho]
      and [Cr] were quantified in various regions of the brains of 8 volunteers, using
      3-dimensional (3D) (1)H-MRS at 1.5 T. The results show that in over 50% of
      approximately 2000 voxels examined, [NAA]/[Cr] and [Cho]/[Cr] exhibited higher
      coefficients of variations (CV) than [NAA] and [Cho] individually. Furthermore,
      in approximately 33% of these voxels, the ratios' CVs exceeded even the combined
      constituents' CVs. Consequently, basing metabolite quantification on ratios and
      assuming stable [Cr] introduces more variability into (1)H-MRS than it prevents.
      Therefore, its cost exceeds the benefit.

PMID- 14599544
TI  - Comparison of TSE, TGSE, and CPMG measurement techniques for MR polymer gel
      dosimetry.
AB  - A radiation dose distribution that optimally conforms to the target volume is of
      major interest for stereotactic radiotherapy. For this purpose treatment plans
      have to be verified experimentally before transferring to the patient. The
      requirements regarding dose accuracy and spatial resolution can be fulfilled with
      tissue equivalent polymer gel dosimeters which offer the possibility to visualize
      3D dose distributions. Herewith, dosimetry can be performed by the spin-spin
      relaxation rate R2 which varies with the absorbed dose. In this work, different
      MR measurement techniques were evaluated: The standard Carr-Purcell-Meiboom-Gill
      (CPMG) method, a modified Turbo-Spin-Echo (TSE) sequence, and a modified Turbo
      Gradient-Spin-Echo (TGSE) sequence. Experiments were performed both with a
      homogeneous water phantom and an irradiated polymer gel. The results show that
      TGSE and especially TSE are suited well for MR polymer gel dosimetry: The
      acquisition time of both techniques can be reduced in comparison to CPMG by a
      factor of 5. The accuracy of dose determination for doses between 2 Gy and 13 Gy
      lies between 5.6% and 2.0% (TSE), 9.0% and 3.2% (TGSE), and 7.9% and 2.7% (CPMG).
      These investigations show that especially TSE can be handled as a substitute or
      at least an alternative to CPMG for the verification of treatment plans in
      stereotactic radiotherapy.

PMID- 14599545
TI  - Cross-talk between Bcr-Abl tyrosine kinase, protein kinase C and telomerase-a
      potential reason for resistance to Glivec in chronic myelogenous leukaemia.
AB  - To prevent the resistance to Glivec in patients with chronic myelogenous
      leukaemia (CML), it is necessary to get a good understanding of its potential
      mechanisms. The present hypothesis accents on the mechanisms whereby Bcr-Abl
      tyrosine kinase remains inhibited by Glivec, but alternative signalling pathways
      become activated-the potential reason associates with activation of telomerase
      after long-term treatment with Glivec and recovery of cell proliferation and
      immortality. The hypothesis is based on the observations about differences in
      telomere dynamics and telomerase activity between chronic and blast phases of CML
      patients, as well as about the potential effect of Glivec on the cross-talk
      between telomerase, Bcr-Abl tyrosine kinase and protein kinase C family-key
      enzymes in CML. It proceeds from recently published data, demonstrating that
      protein kinase C activates and c-Abl tyrosine kinase inhibits telomerase. During
      optimization of chemical structure, Glivec loose its effect on protein kinase C
      and enhances the effect on Bcr-Abl tyrosine kinase, resulting in a high potential
      to activate telomerase indirectly through its effect on both kinases.
      Experimental preclinical data are given in confirmation of this hypothesis.

PMID- 14599546
TI  - LAV694, a new antiproliferative agent showing improved skin tolerability vs.
      clinical standards for the treatment of actinic keratosis.
AB  - The skin tolerability of the tubulin polymerisation inhibitor LAV694 was compared
      to that of 5% 5-fluorouracil (5-FU) and 0.5% podophyllotoxin in vitro using a
      human reconstructed epidermis (HRE), and in vivo using minipigs. Topical
      treatment of HRE for 1 or 3 days with a 0.2, 0.6 or 1% LAV694 cream or the
      placebo showed no signs of irritation in terms of morphology, cell viability
      (lactate dehydrogenase leakage) or interleukin-8 mRNA expression and release. 5
      FU increased interleukin-8 production and induced morphological signs of
      irritation. The substances were also applied under occlusion to the back of two
      minipigs, twice daily, for 9 days to allow intraindividual comparison of skin
      effects and tolerability. Skin reactions were monitored by visual scoring,
      chromometry, pro-inflammatory activity, cell cycle and apoptosis by RT-PCR, laser
      scanning cytometry and histopathological examination of biopsies. Application of
      podophyllotoxin and 5-FU had to be stopped on days 4 and 8, respectively, due to
      severe skin lesions. LAV694 (1%) induced only moderate skin reddening after 9
      days. 5-FU and podophyllotoxin, but not LAV694, increased mRNA expression of pro
      inflammatory cytokines. LAV694 arrested keratinocytes in the M phase of the cell
      cycle and apoptosis was detected histologically in the basal layer. LAV694
      increased the expression of pro-apoptotic genes in both experimental models. In
      conclusion, LAV694 selectively induced apoptosis, rather than necrosis, of growth
      arrested keratinocytes, thus avoiding the occurrence of extensive inflammation.
      This resulted in an improved skin tolerability in comparison with 5-FU and
      podophyllotoxin.

PMID- 14599547
TI  - Alteration of A(3) adenosine receptors in human neutrophils and low frequency
      electromagnetic fields.
AB  - The present study was designed to evaluate the binding and functional
      characterization of A(3) adenosine receptors in human neutrophils exposed to low
      frequency, low energy, pulsing electromagnetic fields (PEMFs). Great interest has
      grown concerning the use of PEMF in the clinical practice for therapeutic
      purposes strictly correlated with inflammatory conditions. Saturation experiments
      performed using the high affinity and selective A(3) adenosine antagonist 5N-(4
      methoxyphenyl-carbamoyl)amino-8-propyl-2-(2-furyl)pyrazolo-[4,3-e]-1,2,4
      triazolo[1,5-c]pyrimidine ([3H]-MRE 3008F20) revealed a single class of binding
      sites with similar affinity in control and in PEMF treated human neutrophils
      (K(D)=2.36+/-0.16 and 2.45+/-0.15 nM, respectively). PEMFs treatment revealed
      that the receptor density was statistically increased (P<0.01) (B(max)=451+/-18
      and 736+/-25fmolmg(-1) protein, respectively). Thermodynamic data indicated that
      [3H]-MRE 3008F20 binding in control and in PEMF-treated human neutrophils was
      entropy and enthalpy driven. Competition of radioligand binding by the high
      affinity A(3) receptor agonists, N(6)-(3-iodo-benzyl)-2-chloro-adenosine-5'-N
      methyluronamide (Cl-IB-MECA) and N(6)-(3-iodo-benzyl)adenosine-5'-N-methyl
      uronamide (IB-MECA), in the absence of PEMFs revealed high and low affinity
      values similar to those found in the presence of PEMFs. In both experimental
      conditions, the addition of GTP 100 microM shifted the competition binding curves
      of the agonists from a biphasic to a monophasic shape. In functional assays Cl-IB
      MECA and IB-MECA were able to inhibit cyclic AMP accumulation and their potencies
      were statistically increased after exposure to PEMFs. These results indicate in
      human neutrophils treated with PEMFs the presence of significant alterations in
      the A(3) adenosine receptor density and functionality.

PMID- 14599548
TI  - Relationship between elevated levels of the alpha 1 acid glycoprotein in chronic
      myelogenous leukemia in blast crisis and pharmacological resistance to imatinib
      (Gleevec) in vitro and in vivo.
AB  - The Abl tyrosine kinase inhibitor imatinb is becoming a standard for the
      treatment of chronic myelogenous leukemia (CML). However, Bcr-Abl gene mutations
      have been reported mainly in relapsing or resistant patients. In primary
      resistant patients, only few mutations have been documented so far, suggesting
      alternative mechanisms. We aimed to investigate if alpha 1 acid glycoprotein
      (AGP), an acute phase drug binding protein, could be a biological marker for
      pharmacological resistance to imatinib in nine patients in acute phase CML. All
      patients (3/3) with high AGP dosages (2.31+/-0.17 mg/mL; normal values, 0.5
      1.3mg/mL) were primary resistant to imatinib whereas an early clinical response
      was observed for the six patients with normal AGP levels (1.13+/-0.2mg/mL). No
      mutation in the adenosine triphosphate domain of Abl were detected before the
      initiation of imatinib therapy. By using in vitro tests combining various
      imatinib concentrations (1-10 microM) with purified human AGP (1 and 3 mg/mL), we
      demonstrate that imatinib-induced apoptosis of K562 or fresh leukemic CML cells
      is abrogated or reduced. The same effect was observed using sera from donors with
      high AGP levels (1.9-3.28 mg/mL). In patients with CML in blastic phase, AGP
      levels could reflect pharmacological resistance to imatinib, suggesting that
      increased dosage of imatinib or the use of a competitor to drug binding should be
      recommended to optimize the therapeutic effect of the drug.

PMID- 14599549
TI  - Effects of Li(+) transport and Li(+) immobilization on Li(+)/Mg(2+) competition
      in cells: implications for bipolar disorder.
AB  - Li(+)/Mg(2+) competition has been implicated in the therapeutic action of Li(+)
      treatment in bipolar illness. We hypothesized that this competition depended on
      cell-specific properties. To test this hypothesis, we determined the degree of
      Li(+) transport, immobilization, and Li(+)/Mg(2+) competition in lymphoblastomas,
      neuroblastomas, and erythrocytes. During a 50 mM/L Li(+)-loading incubation,
      Li(+) accumulation at 30 min (mmoles Li(+)/L cells) was the greatest in
      lymphoblastomas (11.1+/-0.3), followed by neuroblastomas (9.3+/-0.5), and then
      erythrocytes (4.0+/-0.5). Li(+) binding affinities to the plasma membrane in all
      three cell types were of the same order of magnitude; however, Li(+)
      immobilization in intact cells was greatest in neuroblastomas and least in
      erythrocytes. When cells were loaded for 30 min in a 50 mM/L Li(+)-containing
      medium, the percentage increase in free intracellular [Mg(2+)] in neuroblastoma
      and lymphoblastoma cells ( approximately 55 and approximately 52%, respectively)
      was similar, but erythrocytes did not exhibit any substantial increase (
      approximately 6%). With the intracellular [Li(+)] at 15 mM/L, the free
      intracellular [Mg(2+)] increased by the greatest amount in neuroblastomas (
      approximately 158%), followed by lymphoblastomas ( approximately 75%), and then
      erythrocytes ( approximately 50%). We conclude that Li(+) immobilization and
      transport are related to free intracellular [Mg(2+)] and to the extent of
      Li(+)/Mg(2+) competition in a cell-specific manner.

PMID- 14599550
TI  - Suppression of RelA/p65 transactivation activity by a lignoid manassantin
      isolated from Saururus chinensis.
AB  - In our search for NF-kappaB inhibitors from natural resources, we have previously
      identified two structurally related dilignans, manassantin A and B as specific
      inhibitors of NF-kappaB activation from Saururus chinensis. However, their
      molecular mechanism of action remains unclear. We here demonstrate that
      manassantins A and B are potent inhibitors of NF-kappaB activation by the
      suppression of transciptional activity of RelA/p65 subunit of NF-kappaB. These
      compounds significantly inhibited the induced expression of NF-kappaB reporter
      gene by LPS or TNF-alpha in a dose-dependent manner. However, these compounds did
      not prevent the DNA-binding activity of NF-kappaB assessed by electrophoretic
      mobility shift assay as well as the induced-degradation of IkappaB-alpha protein
      by LPS or TNF-alpha. Further analysis revealed that manassantins A and B dose
      dependently suppressed not only the induced NF-kappaB activation by
      overexpression of RelA/p65, but also transactivation activity of RelA/p65.
      Furthermore, treatment of cells with these compounds prevented the TNF-alpha
      induced expression of anti-apoptotic NF-kappaB target genes Bfl-1/A1, a
      prosurvival Bcl-2 homologue, and resulted in sensitizing HT-1080 cells to TNF
      alpha-induced cell death. Similarly, these compounds also suppressed the LPS
      induced inducible nitric oxide synthase expression and nitric oxide production.
      Taken together, manassantins A and B could be valuable candidate for the
      intervention of NF-kappaB-dependent pathological condition such as inflammation
      and cancer.

PMID- 14599551
TI  - Some anti-chronic inflammatory compounds are DNA polymerase lambda-specific
      inhibitors.
AB  - We previously reported that a phenolic compound, petasiphenol, was a selective
      inhibitor of DNA polymerase lambda (pol lambda) in vitro. We found here that
      another phenolic compound, curcumin (diferuloylmethane), which is known as an
      anti-chronic inflammatory agent and is structurally quite similar to
      petasiphenol, was also a potent pol lambda inhibitor. The IC(50) values of
      petasiphenol and curcumin were 7.8 and 7.0 microM, respectively. Curcumin, as
      well as petasiphenol, did not influence the activities of replicative DNA
      polymerases, such as alpha, gamma, delta, and epsilon, but also showed no effect
      even on the pol beta activity belonging to the X family. Curcumin could prevent
      the growth of human NUGC-3 cancer cells with LD(50) values of 13 microM, and
      halted them at the G2/M phase in the cell cycle, whereas petasiphenol suppressed
      the cell growth at 66 microM and arrested the cells at the G1 phase. These data
      showed that curcumin and petasiphenol were slightly different functionally. We
      also previously reported that novel anti-inflammatory terpeno benzoic acids and
      triterpenoids were inhibitors of mammalian DNA polymerases. They could also
      efficiently inhibit the pol lambda activity, although they influenced the other
      polymerase species to the same extent, suggesting that there may be a
      physiological relationship between pol lambda inhibition and anti-12-O
      tetradecanoylphorbol-13-acetate-induced inflammation. Expectedly, petasiphenol
      also showed an anti-12-O-tetradecanoylphorbol-13-acetate-induced inflammatory
      effect in mice. This finding may provide clues to investigating the molecular
      mechanism of inflammation.

PMID- 14599553
TI  - A(2A) adenosine receptor ligands and proinflammatory cytokines induce PC 12 cell
      death through apoptosis.
AB  - A(2A) adenosine receptor-mediated signaling affects a variety of important
      processes in the central nervous system both in physiological and pathological
      conditions, and has been indicated as possible novel therapeutic target in
      several nervous system diseases. In the present work, cell death induction was
      investigated after neuronal PC 12 cell treatment with proinflammatory cytokines
      and adenosine receptor ligands. Interleukin-1-beta (IL-1-beta, 500 U/mL), tumor
      necrosis factor-alpha (TNF-alpha, 1000 U/mL) and the non selective adenosine
      receptor agonist, 5'-N-ethylcarboxamidoadenosine (NECA), caused a significant
      reduction of cell viability with a maximal effect within 3-48 hr. Moreover, an
      addictive effect was detected when the cells were simultaneously treated with
      Interleukin-1-beta and NECA for 3 hr. To investigate the adenosine receptor
      subtypes involved in PC 12 cell death, the effects of several adenosine receptor
      agonists/antagonists were evaluated. The endogenous nucleoside, adenosine, and
      the selective A(2A) adenosine receptor agonist, 2
      (carboxyethylphenylethylamino)adenosine-5'-carboxamide (CGS21680) reduced PC 12
      cell viability. This effect was counteracted by the selective A(2A) adenosine
      receptor antagonist, 7-(2-phenylethyl)-5-amino-2-(2-furyl)-pyrazolo-[4,3e]-1,2,4
      triazolo[1,5c]pyrimidine (SCH58261), but not by selective A(2B) adenosine
      receptor antagonist N-(4-acethylphenyl)-2-[4-(2,3,6,7-tetrahydro-2,6-dioxo-1,3
      dipropyl-1H-purin-8-yl)phenoxy]acetamide (MRS1706), suggesting the specific
      involvement of A(2A) adenosine receptor subtype in adenosine-mediated
      cytotoxicity. Moreover, the selective A(1) adenosine receptor agonist, N(6)
      cyclohexyladenosine (CHA), did not induce any significant effect on cell
      viability. By ELISA immunoassay cell death detection and transmission electron
      microscopy (TEM) we demonstrated that A(2A) adenosine receptor ligands and
      cytokines induced cell death through an apoptotic pathway. In conclusion, our
      results showed that A(2A) adenosine receptors are involved in the control of PC
      12 cell survival/death and may contribute to modulate cellular activity in
      response to tissue damage associated with inflammatory mediator production.

PMID- 14599552
TI  - Recombinant arginine deiminase as a differential modulator of inducible (iNOS)
      and endothelial (eNOS) nitric oxide synthetase activity in cultured endothelial
      cells.
AB  - Modulation of the extracellular level of arginine, substrate for nitric oxide
      synthetases, is a promising modality to alleviate certain pathological conditions
      where excess nitric oxide (NO) is produced. However, complications arise, as only
      preferential inhibition of the inducible nitric oxide synthetase (iNOS), but not
      endothelial nitric oxide synthetase (eNOS), is desired for the treatment of NO
      over-production. We investigated the effect of arginine deprivation mediated by a
      recombinant arginine deiminase (rADI) on the activity of iNOS and eNOS in an
      endothelial cell line, TR-BBB. Our results demonstrated that cytokine-induced NO
      production depends on the extracellular arginine as substrate. However, if
      sufficient citrulline is present in the medium, A23187-activated NO production by
      eNOS does not rely on extracellular arginine. Treatment with rADI can markedly
      inhibit cytokine-induced NO production via iNOS, but not A23187-activated NO
      production via eNOS. Our results also showed that the decrease of NO production
      by iNOS could be achieved by depleting arginine from the medium even under the
      conditions that would up-regulate iNOS expression. Thus, rADI appears to be a
      novel selective modulator of iNOS activity that may be a used as a tool in the
      study of pathological disorders where NO over-production plays a key role.

PMID- 14599554
TI  - Involvement of advanced lipooxidation end products (ALEs) and protein oxidation
      in the apoptotic actions of nitric oxide in insulin secreting RINm5F cells.
AB  - We have explored the impact of nitric oxide (NO) exposure on oxidation damage of
      lipids, and proteins, and the contribution of this type of damage to the
      activation of the apoptotic program in insulin secreting RINm5F cells. Exposure
      of cells to NO donors and to interleukin-1 beta (IL-1beta) led to generation of
      lipooxidation products such as malondialdehyde (MDA) and 4-hydroxynonenal (4
      HNE). Addition of superoxide dismutase (SOD) and catalase (Cat) to cells
      decreased by 50% MDA and 4-HNE production induced by IL-1beta. Over-expression of
      Mn-SOD in cells conferred a remarkable decrease (75%) in IL-1beta-induced lipid
      peroxidation. These data suggest that peroxynitrite (ONOO(-)) mediates
      peroxidative damage to lipids in this cell system. Inhibitors of advanced
      lipooxidation end products (ALEs) formation such as aminoguanidine (AG) and
      pyridoxamine (PM) prevented partially apoptotic events triggered by NO such as
      DNA fragmentation, caspase-3 activation and cytochrome c release from
      mitochondria. These findings indicate that ALEs are involved in NO-induced
      apoptosis. In fact, NO-induced carbonylation of PARP protein preceded its
      apoptotic degradation and inhibitors of ALEs formation prevented both events. We
      thus propose that carbonylation of proteins is instrumental in linking NO
      dependent lipid oxidation and apoptosis in this cell system.

PMID- 14599555
TI  - Mitigation of tumor necrosis factor alpha cytotoxicity by aurintricarboxylic acid
      in human peripheral B lymphocytes.
AB  - The aims of this study were to ascertain whether aurintricarboxylic acid (ATA),
      an endonuclease inhibitor, known to interfere, with the actions of cytokines such
      as interferons, is able to antagonize the toxic effects produced by tumor
      necrosis factor alpha (TNF-alpha) in human healthy peripheral B lymphocytes and
      try to elucidate the molecular machinery through which this possible antagonism
      takes place. Results evidenced that the balance of survival signals of human B
      lymphocytes in the presence of TNF-alpha was altered by the interaction of TNF
      alpha with a salicylate compound, ATA. Apoptosis effected by TNF-alpha alone was
      suppressed in the presence of ATA, and this effect appeared essentially
      characterized by: (i) phosphorylation of phosphatidylinositol-3 kinase (PI-3K),
      influencing in turn protein kinase B/Akt (Akt) and Bad phosphorylation; (ii)
      nuclear translocation of the nuclear factor kappa B (NF-kappaB) and (iii) nuclear
      translocation of protein kinase C zed (PKCzeta). Reversal of TNF-alpha/ATA
      effects occurred in the presence of the PI-3K specific inhibitors wortmannin or
      LY294002 in the culture medium and was coincident with inhibition of the
      translocation of PKCzeta in the nucleus, while NF-kappaB was less affected. These
      results indicate, therefore, that PI-3K-mediated activation and nuclear transfer
      of PKCzeta might be essential steps of ATA antagonism against TNF-alpha,
      suggesting that possible ATA pharmacological applications might be taken into
      account for staving off systemic or local toxic effects produced by TNF-alpha.

PMID- 14599557
TI  - Inhibitory effect of fucoidan on the activities of crotaline snake venom myotoxic
      phospholipases A(2).
AB  - Myotoxic phospholipases A(2) account for most of the muscle necrosis that results
      from envenenomation by crotaline snakes. In this study, we investigated the
      protective effect of fucoidan, a natural sulfated polysaccharide obtained from
      the brown seaweed Fucus vesiculosus, against the cytotoxic and myotoxic
      activities of a group of phospholipase A(2) myotoxins from crotaline snake
      venoms: Bothrops asper myotoxins I, II, III, and IV, Cerrophidion godmani
      myotoxins I and II, Atropoides nummifer myotoxins I and II, and Bothriechis
      schlegelii myotoxin I. All of the toxins tested were efficiently inhibited by
      fucoidan, in both their cytotoxic and myotoxic effects. The basis for this
      inhibition appears to be the rapid formation of complexes between fucoidan and
      myotoxins, as evidenced by turbidimetric analysis. The possible binding site of
      fucoidan on the myotoxins was investigated using short synthetic peptides that
      represent the membrane-damaging region (residues 115-129) for three of these
      toxins. Fucoidan clearly inhibited the cytolytic activity of the peptides,
      indicating its ability to interact with the C-terminal myotoxic region of these
      phospholipases A(2). Fucoidan significantly inhibited muscle damage in mice, when
      administered locally, immediately after experimental envenomation with crude
      venom from B. asper. These results encourage further studies of sulfated fucans
      as compounds of potential use to improve the treatment of envenomations by
      crotaline snakes.

PMID- 14599556
TI  - Isodiospyrin as a novel human DNA topoisomerase I inhibitor.
AB  - Isodiospyrin is a natural product from the plant Diospyros morrisiana, which
      consists of an asymmetrical 1,2-binaphthoquinone chromophore. Isodiospyrin
      exhibits cytotoxic activity to tumor cell lines but very little is known about
      its cellular target and mechanism of action. Unlike the prototypic human
      topoisomerase I (htopo I) poison camptothecin, isodiospyrin does not induce htopo
      I-DNA covalent complexes. However, isodiospyrin antagonizes camptothecin-induced,
      htopo I-mediated DNA cleavage. Binding analysis indicated that isodiospyrin binds
      htopo I but not DNA. These results suggest that isodiospyrin inhibits htopo I by
      direct binding to htopo I, which limits htopo I access to the DNA substrate.
      Furthermore, isodiospyrin exhibits strong inhibitory effect on the kinase
      activity of htopo I toward splicing factor 2/alternate splicing factor in the
      absence of DNA. Thus, these findings have important implications on
      naphthoquinone and its derivatives' cellular mode of actions, i.e. these novel
      DNA topoisomerase I inhibitors can prevent both DNA relaxation and kinase
      activities of htopo I.

PMID- 14599558
TI  - A non-voltage-gated calcium channel with L-type characteristics activated by B
      cell receptor ligation.
AB  - In mature B cells engagement of the antigen-receptor (BCR) results in a peak of
      Ca(2+) from mobilisation of internal stores followed by a lower but sustained
      elevation that is dependent upon extracellular Ca(2+). The Ca(2+) channel
      involved in the sustained elevation remains uncharacterised. Here we have
      presented evidence that although non-excitable, B cells expressed a BCR-activated
      Ca(2+) channel sharing some properties of conventional L-type voltage-gated
      channels. Human lymphoma B cells expressed a transcript having homology to a
      highly conserved region on the pore-forming alpha(1.2) subunit of L-type voltage
      gated Ca(2+) channels. The alpha(1.2) protein was expressed together with the
      beta1 subunit, while an antibody raised against the extracellular portion of L
      type Ca(2+) channels caused a Ca(2+) flux in these cells. Drugs that block
      classical L-type channels abolished the BCR-induced Ca(2+) flux while directly
      activating a plasma membrane Ca(2+) channel: activation of the channel, separate
      from Ca(2+) influx, inhibited BCR-induced Ca(2+) release from intracellular
      stores. BAYK8644-a drug that binds to open L-type channels-failed to release
      intracellular Ca(2+) in the absence of BCR cross-linking but instantly abolished
      the BCR-induced Ca(2+) peak and established the sustained phase of the response.
      The BCR-activated calcium channel appeared to terminate the initial peak of BCR
      induced Ca(2+) release and initiate the sustained phase of the signal.

PMID- 14599559
TI  - Hepatic expression of cytochrome P450s in hepatocyte nuclear factor 1-alpha
      (HNF1alpha)-deficient mice.
AB  - Hepatocyte nuclear factor 1 alpha (HNF1alpha) is a liver enriched homeodomain
      containing transcription factor that has been shown to transactivate the
      promoters of several cytochrome P450 (CYP) genes, including CYP2E1, CYP1A2,
      CYP7A1, and CYP27, in vitro. In humans, mutations in HNF1alpha are linked to the
      occurrence of maturity onset diabetes of the young type 3, an autosomal dominant
      form of non-insulin-dependent diabetes mellitus in which afflicted subjects
      generally develop hyperglycemia before 25 years of age. Mice lacking HNF1alpha
      also develop similar phenotypes reminiscent of non-insulin-dependent diabetes
      mellitus. To investigate a potential role for HNF1alpha in the regulation of CYPs
      in vivo, the expression of major CYP genes from each family was examined in the
      livers of mice lacking HNF1alpha. Analysis of CYP gene expression revealed marked
      reductions in expression of Cyp1a2, Cyp2c29 and Cyp2e1, and a moderate reduction
      of Cyp3a11. In contrast Cyp2a5, Cyp2b10 and Cyp2d9 expression were elevated.
      There are also significant changes in the expression of genes encoding CYPs
      involved in fatty acid and bile acid metabolism characterized by a reduction in
      the expression of Cyp7b1, and Cyp27 as well as elevations in Cyp4a1/3, Cyp7a1,
      Cyp8b1, and Cyp39a1 expression. These results point to a critical role for
      HNF1alpha in the regulation of CYPs in vivo and suggest that this transcription
      factor may have an important influence on drug metabolism as well as lipid and
      bile acid homeostasis in maturity onset diabetes of the young type 3 diabetics.

PMID- 14599560
TI  - Targeting oxidative stress-related diseases: organochalcogen catalysts as redox
      sensitizers.
AB  - Tumor cells proliferate under conditions of oxidative stress. A novel therapeutic
      approach would be to enhance the cellular effects of the reactive oxygen species
      formed under these conditions by supplementation with a redox catalyst. This
      provides a means to target and specifically destroy cancer cells via oxidation of
      redox-sensitive proteins, such as transcription factors, while leaving cells with
      a normal redox balance largely unaffected. We have previously reported a
      preliminary observation on the effects of pro-oxidant catalysts that enhance
      cancer cell death. This paper presents a detailed in vitro investigation into the
      mechanism of action of synthetic glutathione peroxidase mimics on a model Sp1
      transcription factor peptide. The structure and redox potential of these mimics
      correlate with their ability to catalyze the oxidation of this zinc-binding motif
      by H(2)O(2) and these compounds promise therapeutic potential by promoting
      H(2)O(2)-induced PC12 cell death.

PMID- 14599561
TI  - Pharmacologic or genetic ablation of maleylacetoacetate isomerase increases
      levels of toxic tyrosine catabolites in rodents.
AB  - Dichloroacetate (DCA) is both an environmental contaminant and an investigational
      drug for diseases involving perturbed mitochondrial energetics. DCA is
      biotransformed to glyoxylate by maleylacetoacetate isomerase (MAAI). Previous
      studies have shown that DCA decreases MAAI activity in rat liver in a time- and
      dose-dependent manner and may target the protein for degradation in vivo. We now
      report that the MAAI protein is depleted in a time- and dose-dependent manner in
      the livers of Sprague-Dawley rats exposed to DCA. This decrease in protein
      expression is not mirrored by a decrease in the steady-state levels of MAAI mRNA,
      indicating that the depletion is exclusively a post-transcriptional event. We
      also investigated the pharmacokinetics of DCA in the recently developed MAAI
      knockout (MAAI-KO) mouse. MAAI-KO mice maintain high plasma and urine drug
      concentrations and do not biotransform DCA to monochloroacetate to a significant
      extent. Therefore, no alternative pathways for DCA clearance appear to exist in
      mice other than by MAAI-mediated biotransformation. DCA-nai;ve MAAI-KO mice
      accumulate very high levels of the tyrosine catabolites maleylacetone and
      succinylacetone, and DCA exposure did not significantly increase the levels of
      these compounds. MAAI-KO mice also have high levels of fumarylacetone and normal
      levels of fumarate. These results demonstrate that pharmacologic or genetic
      ablation of MAAI cause potentially toxic concentrations of tyrosine intermediates
      to accumulate in mice and perhaps in other species.

PMID- 14599562
TI  - The galloyl moiety of green tea catechins is the critical structural feature to
      inhibit fatty-acid synthase.
AB  - It has been reported that inhibition of fatty-acid synthase (FAS) is selectively
      cytotoxic to human cancer cells. Considerable interest has developed in
      identifying novel inhibitors of this enzyme complex. Our previous work showed
      that green tea (-)-epigallocatechin gallate can inhibit FAS in vitro. To
      elucidate the structure-activity relationship of the inhibitory effects of tea
      polyphenols, we investigated the inhibition kinetics of the major catechins and
      analogues. Ungallated catechins from green tea do not show obvious inhibition
      compared with gallated catechins. Another gallated catechin, (-)-epicatechin
      gallate, was also found as a potent inhibitor of FAS and its inhibition
      characteristics are similar to (-)-epigallocatechin gallate. Furthermore, the
      analogues of galloyl moiety without the catechin skeleton such as propyl gallate
      also showed obvious slow-binding inhibition, whereas the green tea ungallated
      catechin not. Atomic orbital energy analyses suggest that the positive charge is
      more distinctly distributed on the carbon atom of ester bond of galloyl moiety of
      gallate catechins, and that gallated forms are more susceptible for a
      nucleophilic attack than other catechins. Here we identify the galloyl moiety of
      green tea catechins as critical in the inactivation of the ketoacyl reductase
      activity of FAS for the first time.

PMID- 14599563
TI  - Expression of heme oxygenase-1 and regulation by cytokines in human
      osteoarthritic chondrocytes.
AB  - Heme oxygenase-1 (HO-1) is implicated in the protection against tissue injury. We
      investigated the expression of this protein in cartilage sections and
      chondrocytes obtained from osteoarthritic patients. HO-1 was immunodetected in
      preparations from cartilage and also in chondrocytes cultured in the absence of
      stimulation. We found that HO-1 can be modulated by cytokines since the pro
      inflammatory cytokines interleukin (IL)-1beta, IL-17 and tumour necrosis factor
      alpha (TNF-alpha) down-regulated this protein, whereas the anti-inflammatory
      cytokine IL-10 exerted the opposite effect. Our results suggest a role for HO-1
      as part of protective mechanisms against tissue injury in human cartilage.

PMID- 14599564
TI  - Inhibitory action of ICI-182,780, an estrogen receptor antagonist, on BK(Ca)
      channel activity in cultured endothelial cells of human coronary artery.
AB  - ICI-182,780 is known to be a selective inhibitor of the intracellular estrogen
      receptors. The effect of ICI-182,780 on ion currents was studied in cultured
      endothelial cells of human coronary artery. In whole-cell current recordings, ICI
      182,780 reversibly decreased the amplitude of K(+) outward currents. The decrease
      in outward current caused by ICI-182,780 could be counteracted by further
      application of magnolol or nordihydroguaiaretic acid, yet not by 17beta
      estradiol. Under current-clamp condition, ICI-182,780 (3microM) depolarized the
      membrane potentials of the cells, and magnolol (10 microM) or
      nordihydroguaiaretic acid (10 microM) reversed ICI-182,780-induced
      depolarization. In inside-out patches, ICI-182,780 added to the bath did not
      alter single-channel conductance of large-conductance Ca(2+)-activated K(+)
      channels (BK(Ca) channels), but decreased their open probability. ICI-182,780
      reduced channel activity in a concentration-dependent manner with an IC(50) value
      of 3 microM. After BK(Ca) channel activity was suppressed by 2-methoxyestradiol
      (3 microM), subsequent application of ICI-182,780 (3 microM) did not further
      reduce the channel activity. The application of ICI-182,780 shifted the
      activation curve of BK(Ca) channels to positive potentials. Its decrease in the
      open probability primarily involved a reduction in channel open duration. ICI
      182,780 also suppressed the proliferation of these endothelial cells with an
      IC(50) value of 2 microM. However, in coronary smooth muscle cells, a bell-shaped
      concentration-response curve for the ICI-182,780 effect on BK(Ca) channel
      activity was observed. This study provides evidence that ICI-182,780 can inhibit
      BK(Ca) channels in vascular endothelial cells in a mechanism unlikely to be
      linked to its anti-estrogen activity. The inhibitory effects on these channels
      may partly contribute to the underlying mechanisms by which ICI-182,780 affects
      endothelial function.

PMID- 14599566
TI  - Expression of kynurenine aminotransferases in the rat retina during development.
AB  - The study investigates the cellular expression of kynurenine aminotransferases
      (KAT I and II) in the rat retina during development. At P1 (the day of birth) and
      P7 (the 7th day after birth), KAT I expression was observed in the inner
      plexiform layer (IPL), the fiber layer (FL), and in vertically running processes
      in the ganglion cell layer (GCL) (but not in the cell bodies). At P14 (the 14th
      day after birth) a strong KAT I immunoreactivity was observed in Muller cell
      endfeet. KAT II was expressed in the IPL, the FL, and in cells in the GCL at P1
      and P7. From P14 on, KAT II expression in the IPL decreased. Double labeling
      revealed that KAT I was expressed in Muller cell endfeet, whilst KAT II both on
      retinal ganglion cells (RGC) and Muller cell endfeet. In conclusion, KAT I and II
      are present in the rat retina during development. The heterogeneity of the KAT
      developmental profiles possibly reflects a neuromodulatory role in the retinal
      differentiation.

PMID- 14599567
TI  - The relationship between full field electroretinogram and perimetry-like visual
      thresholds in RCS rats during photoreceptor degeneration and rescue by cell
      transplants.
AB  - Dark-adapted full field electroretinogram (ERG) and visual receptive field
      thresholds (recorded from the superior colliculus) were correlated in a model of
      retinal degeneration, the Royal College of Surgeons rat. In both untreated and
      retinal pigment epithelium cell transplanted rats, optimal correlation was
      between b-wave amplitude and preserved visual field area with thresholds under a
      defined level. The work shows that the magnitude of the b-wave can be used to
      predict the computed area and degree of visual field preservation recorded in the
      central nervous system. These observations validate using ERG to assess residual
      visual function and the effect of transplantation.

PMID- 14599568
TI  - The spatiotemporal precision of ganglion cell signals: a comparison of
      physiological and psychophysical performance with moving gratings.
AB  - Comparison of the spatiotemporal information delivered by ganglion cells with
      human psychophysical performance may give insight to how retinal information is
      utilized by cortical mechanisms, and constrain models of spatiotemporal
      processing. Ganglion cells' responses were measured with drifting gratings of
      various spatial and temporal frequencies and contrasts. The spatiotemporal
      precision of cell responses was estimated in terms of a noise measure and phase
      variation, and compared to human vernier performance. Noise and phase variation
      of magnocellular (MC) cells was least at low temporal frequencies, despite their
      transient responses. The patterns of spatiotemporal precision of MC cells
      resembled the patterns of human vernier thresholds while those of parvocellular
      cells did not, implying use of MC cells' signals in these tasks. The analysis
      further implied that cortical mechanisms must perform a sophisticated
      spatiotemporal analysis over local ganglion cell arrays.

PMID- 14599569
TI  - Brightness contrast and assimilation from patterned inducing backgrounds.
AB  - Theories of induction propose that the brightness of a test patch within a
      complex surround is explained by local contrast or by integrating contrasts from
      various regions within the surround, weighted inversely with the distance from
      the test. Results here corroborate that brightness induction from a patterned
      background depends on both contiguous and non-contiguous surrounding light, but
      the measurements were inconsistent with any linear integration of contrast at
      edges within the scene. In some conditions, assimilation rather than contrast to
      contiguous surrounding light was observed, depending on the luminance of the
      light in non-contiguous regions. This finding implies that brightness induction
      from patterned backgrounds depends on neural processes that can cause contrast
      and/or assimilation, depending on the luminance relation between contiguous and
      non-contiguous regions. A model in the literature postulating that the influence
      of a non-contiguous edge is regulated by the amount of contrast at the contiguous
      edge can accommodate brightness induced by these patterned backgrounds.

PMID- 14599570
TI  - Both monocular and binocular signals contribute to motion rivalry.
AB  - There is an ongoing debate on whether binocular rivalry involves competition
      among monocular cells or binocular cells. We investigated this issue
      psychophysically with two specially designed test stimuli. One test stimulus
      contained monocular motion signals but greatly reduced binocular motion signals,
      while the other contained binocular motion signals but no monocular motion
      signals. For comparison, we also employed a normal rivalrous control containing
      both monocular and binocular motion signals, and a non-rivalrous flicker-noise
      control with neither monocular nor binocular motion signals. We found that
      binocular rivalry for the two test stimuli was significantly reduced compared
      with the normal rivalrous control, but not completely eliminated compared with
      the non-rivalrous control. Therefore, both monocular and binocular motion signals
      appear to contribute to motion rivalry, suggesting that motion rivalry must
      involve competition among both monocular and binocular cells.

PMID- 14599571
TI  - Effects of contrast and size on orientation discrimination.
AB  - Motivated by the recent physiological finding that a neuron's receptive field can
      increase in size by a factor of 2-4-fold at low contrast [Nat. Neurosci. 2 (1999)
      733, Proc. Natl. Acad. Sci. USA 96 (1999) 12073], we sought to examine whether a
      psychophysical task might reflect the contrast dependent changes in the
      size/structure of a receptive field. We postulate that since spatial summation is
      not contrast invariant, a task that relies on the spatial structure of a
      receptive field, such as orientation discrimination, should also be affected by
      changes in contrast. Previously, orientation discrimination thresholds have been
      reported to be roughly independent of the contrast of a stimulus for most of the
      visible range of contrasts [i.e. J. Neurophysiol. 57 (1987) 773, J. Opt. Soc. Am.
      6 (1989) 713, Vis. Res. 30 (1990) 449, Vis. Res. 39 (1999) 1631]. Here, we found
      large improvements in orientation discrimination with contrast that were
      dependent on stimulus area. Furthermore, the apparent constancy of orientation
      discrimination for large area stimuli is possibly a result of a floor effect on
      the threshold. Therefore we conclude that there is not strong evidence for
      contrast invariant orientation discrimination. We interpret these results in the
      context of recent neurophysiological results about the expansion of cortical
      cells' receptive fields at low contrast.

PMID- 14599572
TI  - Spatial attention and object-based attention: a comparison within a single task.
AB  - There is now much experimental evidence supporting the idea that visual attention
      can be deployed in at least two ways: one space-based and other object-based.
      However, it is not clear whether space- and object-based attention work in an
      integrated way within the visual system. In this article, we present two
      experiments in which we compare both components of attention within a cueing
      paradigm. Participants had to discriminate the orientation of a line that
      appeared within one of four moving circles, differing in colour. A cue appearing
      close to one of the four circles indicated the location or circle where the
      target stimulus was likely to appear. Spatial and object cueing effects were
      observed: responses were faster when target appeared either at the precued
      location or within the precued object. In addition, the object-cueing effect
      occurred only when the cue was spatially invalid and not when it was spatially
      valid. These results suggest that object- and space-based attention interact,
      with selection by location being primary over object-based selection.

PMID- 14599573
TI  - Discrimination of oriented visual textures by poultry chicks.
AB  - We investigated how poultry chicks discriminate textures of lines sharing a
      common orientation from textures of variably oriented lines. Stimulus colours
      along with illumination were adjusted to selectively stimulate different receptor
      mechanisms. Chicks could discriminate achromatic textures, but not textures
      isoluminant to the double cones that gave a long vs. medium wavelength chromatic
      signal, nor an intensity signal for the short and very-short wavelength cones.
      These results suggest that detection of line orientation and texture
      discrimination uses an achromatic signal derived either from the double cones, or
      summed outputs of long and medium wavelength sensitive single cones.

PMID- 14599574
TI  - A role for contrast-normalisation in second-order motion perception.
AB  - Two low-level motion models are applied to a second-order stimulus, a translating
      contrast modulation of static binary noise. Both models have been used to
      demonstrate equivalence between energy and gradient algorithms and can be split
      into a motion-opponent stage followed by a contrast-normalised stage. Analysis of
      results shows no directional bias at the motion-opponent stage but a strong bias,
      indicating the correct direction of second-order motion, at the contrast
      normalised stage. This demonstrates that the intrinsically non-linear process of
      contrast-normalisation may play a part in the detection of second-order motion.

PMID- 14599575
TI  - Pigment epithelial changes in a strain of pigmented rabbits with low ERG b-wave
      amplitudes.
AB  - Retinas from a strain of rabbits with low dark-adapted electroretinographic (ERG)
      b-wave amplitudes, and declining ERG responses with time, were examined by light
      and electron microscopy. Seven rabbits from the affected strain (13 months to 5
      years old) and six control animals (6-26 months old) were included in the study.
      Small inclusions with an electron dense border, about 0.2-1.5 microm in diameter,
      were significantly (p<0.01) more numerous within the retinal pigment epithelial
      (RPE) cells in the affected rabbits than in the control animals. No morphological
      evidence of retinal degeneration was found. Further studies are needed to
      establish the functional defect in this strain of rabbits.

PMID- 14599576
TI  - The multifocal pattern electroretinogram in glaucoma.
AB  - BACKGROUND: The pattern ERG can be used to detect early glaucomatous change,
      because the response of cells in the inner retina from (typically) 20 degrees -40
      degrees of area is reduced before perimetric abnormality is certain. The
      multifocal pattern electroretinogram (mfPERG) allows analysis of many local
      regions within this area. The aim of this study was to investigate whether in
      patients with presumed glaucoma the mfPERG permits diagnosis and discrimination
      from normals. METHODS: Measurements on 25 age-related normal eyes were compared
      to those on 23 eyes with different stages of glaucoma. A RETIScan system was used
      to generate a stimulus pattern of 19 hexagons, each consisting of six triangles.
      The triangles pattern-reversed black to white at 75 Hz. Those 19 hexagons were
      grouped into three stimulus regions: a central field, a middle, and a peripheral
      ring. The complete array subtended 48 degrees at the eye. The hexagons alternated
      between black and white, in a temporal pattern that followed a corrected binary m
      sequence (length 512, 10 cycles with 39 s each). The amplitudes and latencies of
      positive responses at approximately 50 ms (P-50) and negative responses at
      approximately 95 ms (N-95) were analyzed. RESULTS: In patients with glaucoma the
      P-50 and N-95 components of the mfPERG were significantly reduced for the central
      area and both outer rings compared to normal volunteers (p<0.001, Mann-Whitney
      U). The most distinct reduction was observed for N-95 and the central ring.
      Changes in latencies were not conclusive. The reduction of the components
      increased with the stage of glaucoma. A predictive model for detecting early
      glaucomatous changes was designed based on P-50-N-95 with 88% sensitivity and 76%
      specificity. CONCLUSION: In glaucoma a marked reduction of components, especially
      centrally is observed in the mfPERG. This hints to an early involvement of
      central ganglion cells and may be useful for future functional tests.

PMID- 14599577
TI  - Potato starch granule nanostructure studied by high resolution non-contact AFM.
AB  - Surface studies at ambient conditions of potato starch granules subjected to
      multiple freezing and thawing, performed by a high resolution non-contact atomic
      force microscopy (nc-AFM), revealed some details of the starch granule
      nanostructure. After the treatment, a significant separation and a chain-like
      organisation of the granule surface elements have been observed. An accurate
      analysis of the granule surface nanostructure with a single amylopectine cluster
      resolution could be carried out. The oblong nodules of approximately 20-50 nm in
      diameter have been observed at the surface of the potato starch granules. The
      same size particles were precipitated by ethanol from gelatinized potato starch
      suspensions. They were also detected at the surface of oat and wheat starch
      granules. After multiple freezing and thawing, the eroded potato granule surface
      revealed a lamellar structure of its interior. The 30-40 nm inter-lamellar
      distances were estimated by means of nc-AFM. These findings fit previously
      proposed dimensions of the structural elements in the crystalline region of the
      starch granule. The observed surface sub-particles might correspond to the single
      amylopectine side chain clusters bundled into larger blocklets packed in the
      lamellae within the starch granule. The results supported the blocklet model of
      the starch granule structure.

PMID- 14599578
TI  - Structural studies of the mix-linked beta-(1-->3)/beta-(1-->4)-D-xylans from the
      cell wall of Palmaria palmata (Rhodophyta).
AB  - The structure and organization of Palmaria palmata cell walls, which are largely
      involved in biological and physiological functions as well as in biotechnological
      and food applications of this red marine alga, are principally assumed by the
      interactions and linkages of major mix-linked beta-(1-->3)/beta-(1-->4)-D-xylans.
      These partly acidic polysaccharides are essentially held in the cell wall by H
      bonds. The location of the acid groups and the distribution of 1-->3-linkage were
      studied following the endo-beta-(1,4)-xylanase hydrolysis of sequentially
      extracted xylans, and fine analysis of the oligosaccharides produced by anion
      exchange chromatography, high performance anion exchange chromatography (HPAEC)
      PAD, nuclear magnetic resonance (NMR) and electrospray ion trap mass spectrometry
      (ESI-MS) techniques. The results indicate that the acidity of the xylans was
      related to potential linkages to sulfated and/or phosphorylated
      xylogalactoprotein complexes. H-bonding of the mix-linked xylans involved a
      regular 1,3-linkages distribution idealized in a pentameric repeating structure
      (one 1,3-linkage and four 1,4-linkages). Furthermore, MS analysis of the xylo
      oligosaccharides revealed a substitution of the mix-linked xylans by a non-osidic
      component of 175 g mol(-1). The presence of this substituent and of the proposed
      covalent linkage between the mix-linked xylans and charged glycoproteins are
      discussed with regard to the polysaccharides interactions in P. palmata cell
      walls.

PMID- 14599579
TI  - Retention of enzyme gene duplicates by subfunctionalization.
AB  - Duplication-degeneration-complementation (DDC) describes a process by which
      evolving duplicates of a pleiotropic ancestral gene divide up the multiple
      functions of the ancestor between them (i.e. subfunctionalize), and this
      ultimately frustrates the rate of pseudogene formation. Focusing explicitly on
      enzyme-like pleiotropic function, we model DDC driven by sequence divergence
      between duplicates. The model incorporates an idealized sequence-function mapping
      in which enzyme-substrate binding affinity is related to hydrophobic versus polar
      (HP) amino-acid composition of tertiary structure about the binding pocket. In
      this sense, a transparent coupling between physical-chemical function of an
      enzyme and sequence evolution is presented.

PMID- 14599580
TI  - A structural characterization of in situ chromatin on cell lines isolated from
      patients affected by ataxia telangiectasia.
AB  - Ataxia telangiectasia (AT) is an autosomal recessive disorder characterized by
      numerous clinical and cellular features. The pleiotropic nature of the AT
      syndrome attests to the multiple roles of ATM, the protein codified by the gene
      altered in AT patients. We investigated if different mutations of ATM could
      reflect on different alterations of nuclear architecture and chromatin
      organization. We selected three lymphoblastoid cell lines isolated from AT
      patients affected by different mutations of ATM gene and one healthy control. We
      characterized the in situ chromatin structure of each cell line by a biophysical
      approach: (1) we evaluated the rearrangements of the chromatin domains at the
      level of single cell by quantitative fluorescence microscopy; (2) we analysed the
      changes of the average chromatin condensation by differential scanning
      calorimetry. The results show that the three different ATM mutations produce
      significant modifications of both nuclear architecture and chromatin
      condensation.

PMID- 14599581
TI  - Studies on the structure of the plant wax nonacosan-10-ol, the main component of
      epicuticular wax conifers.
AB  - The main component presents in the epicuticular waxes of needles of Pinus
      halepensis and the most of conifers, the secondary alcohol nonacosan-10-ol, has
      been investigated by X-ray diffraction and differential scanning calorimetry. The
      results obtained from these physical techniques permitted to establish a
      definitive structural model of the molecular arrangement of this wax, basically
      in good agreement with the model formulated by other authors from theoretical
      formulations. Biological implications of the proposed structure have been also
      formulated.

PMID- 14599582
TI  - Immobilization of polyphenol oxidase in conducting copolymers and determination
      of phenolic compounds in wines with enzyme electrodes.
AB  - Polyphenol oxidase (PPO) was immobilized in copolymers of thiophene
      functionalized menthyl monomer (MM) with pyrrole. Immobilization of enzyme was
      performed via entrapment in conducting copolymers during electrochemical
      polymerization of pyrrole. Maximum reaction rates, Michaelis-Menten constants and
      temperature, pH and operational stabilities of enzyme electrodes were
      investigated. Total amount of phenolic compounds in red wines of Turkey were
      analyzed by using these electrodes.

PMID- 14599583
TI  - Oxidative damage of DNA by the reaction of amino acid with methylglyoxal in the
      presence of Fe(III).
AB  - Methylglyoxal (MG) is an endogenous metabolite which is present in increased
      concentrations in diabetics and reacts with amino acids to form advanced
      glycation end products. DNA cleavage induced by the reaction of MG with lysine in
      the presence of Fe3+ was investigated. When plasmid DNA was incubated with MG and
      lysine in the presence of Fe3+, DNA strand breakage was proportional to MG and
      lysine concentrations. The formation of superoxide anion was detected during this
      reaction, and catalase, hydroxyl radical scavengers and iron chelator,
      desferrioxamine inhibited DNA cleavage. Deoxyribose assays showed that hydroxyl
      radicals were generated during the MG/lysine/Fe3+ reaction. These results suggest
      that superoxide anion and H2O2 may be generated from the glycation reaction
      between lysine with MG, and that Fe3+ probably participates in a Fenton's type
      reaction to produce hydroxyl radicals, which may cause DNA cleavage. This
      mechanism, in part, may provide an explanation for the deterioration of organs
      under diabetic conditions.

PMID- 14599584
TI  - Interactions of tetracycline and its derivatives with DNA in vitro in presence of
      metal ions.
AB  - The interactions of calf thymus DNA with tetracycline (TC), 7-chlorotetracycline
      (CTC) and 6-dimethyl-7-chlorotetracycline (DMTC) were assessed employing
      spectrofluorometric and circular dichroism (CD) techniques. The Scatchard
      analysis revealed relatively lesser binding affinity of TC (Ka= 1.2 x 10(7) lmol(
      1)) vis-a-vis CTC (Ka= 3.4 x 10(7) lmol(-1)) and DMTC (Ka= 3.0 x 10(7) lmol(-1))
      with DNA. The data suggested both the intercalative and electrostatic nature of
      binding between the tetracyclines and DNA. The presence of Cu(II) augmented the
      interaction of tetracyclines with DNA, and resulted in red shift by 12 nm in CD
      spectra of tetracycline. The molar ellipticity (theta) also changed significantly
      for CTC and DMTC. The data unequivocally demonstrated the DNA binding potential
      of tetracyclines both in the presence and absence of Cu(II) ions in dark. The
      enhanced binding of tetracyclines in presence of Cu(II), ensuing conformational
      changes in DNA secondary structure to a varying extent, reflects differential
      reactivity of ligand chromophores.

PMID- 14599585
TI  - Copper sorption by chitosan in the presence of citrate ions: influence of metal
      speciation on sorption mechanism and uptake capacities.
AB  - The presence of organic ligands in a solution containing metal ions modifies
      metal speciation, which in turn changes the sorption mechanism, optimum pH range
      and maximum sorption capacity. The present work investigates the sorption of
      copper by chitosan in the presence of citrate at different metal/ligand ratios.
      Copper uptake in acidic solution takes place through electrostatic attraction
      between the protonated amine groups of chitosan and anionic copper-citrate
      complexes (mainly Cu(OH)L2- but also a small fraction of CuL-). Sorption was
      negligible below pH 3 due to competition from dissociated anionic ligand and
      counter ions brought about by dissociation of the acid used for pH control.
      Actually, copper sorption begins to be significant when the fraction of anionic
      copper-complexes exceeds that of anionic copper-free ligand. So sorption capacity
      strongly increases up to pH 4.5-5.5. Above pH 5.5, the progressive decrease of
      amine protonation leads to a linear decrease in sorption capacity. An excess of
      ligand leads to an increase in the fraction of free dissociated (anionic) ligand
      that may compete for electrostatic attraction on protonated amine groups and
      therefore leads to a decrease in sorption capacities.

PMID- 14599586
TI  - Study of the interactions between lysozyme and a fully-fluorinated surfactant in
      aqueous solution at different surfactant-protein ratios.
AB  - The interactions of a fluorinated surfactant, sodium perfluorooctanoate, with
      lysozyme, have been investigated by a combination of UV absorbance, electrical
      conductivity and dynamic light scattering to detect and to characterize the
      conformational transitions of lysozyme. By using difference spectroscopy, the
      transition was followed as a function of surfactant concentration, and the data
      were analyzed to obtain the Gibbs energy of the transition in water (DeltaGw(o))
      and in a hydrophobic environment (DeltaGh(o)) for saturated protein-surfactant
      complexes. Electrical conductivity was used to determine the critical micelle
      concentration of the surfactant in the presence of different lysozyme
      concentration. From these results, the average number of surfactant monomer per
      protein molecule was calculated. Finally, dynamic light scattering show that only
      changes in the secondary structure of the protein can be observed.

PMID- 14599587
TI  - Effect of methyl alcohol on the morphology and conformational characteristics of
      silk sericin.
AB  - Effects of methyl alcohol on the morphology and conformational characteristics of
      silk sericin (SS) were studied. Scanning electron microscope showed that
      morphology of SS lyophilized was dramatically changed from sponge-like structure
      to spherical fine particle type. X-ray diffraction method, infrared spectroscopy,
      and differential scanning calorimetry showed that the conformation of SS was
      random coil structure regardless of the addition of methyl alcohol. On the other
      hand, circular dichroism showed that the molecular states of SS were more densely
      packed.

PMID- 14599588
TI  - 13C-NMR study of the interaction of bacterial alginate with bivalent cations.
AB  - The effect of bivalent cations on solutions of extracellular polymeric substances
      (EPS) isolated from Pseudomonas aeruginosa was monitored by means of solid-state
      nuclear magnetic resonance. In particular, the binding of Ca2+ and Mg2+ to the
      alginate in aqueous solution was studied by determining the spin-lattice
      relaxation rates, line widths and line shapes of 13C nuclei under variation of
      the ion concentration. Both cations differ strongly in their affinity towards
      bacterial alginate. Spectral data indicate that the strong binding capacity of
      calcium is connected to the formation of a chelate complex, in which binding
      occurs particularly with the monomer units in alternating mannuronate-guluronate
      blocks. In contrast to this, binding of magnesium ions was found to be much
      weaker and non-specific.

PMID- 14599589
TI  - Changes in thermal and electrical properties of bone as a result of 1 MGy-dose
      gamma-irradiation.
AB  - Determination of temperature dependencies of electric conductivity and thermal
      properties by differential scanning calorimetry (DSC) allow to analyse the
      processes of charge and heat transport in the bone being a complex collagen
      hydroxyapatite (HAP)-water system. Modification of the bone structure by high
      doses of gamma-radiation changes the electrical and thermal properties of the
      bone. Electrical conductivity (sigma) of the bone decreases with consecutive
      heating runs. The decrease in sigma observed for irradiated samples was explained
      by the scission of the main chain of collagen macromolecule. Irradiation
      decreased the hydration level in the bone, its denaturation temperature and
      increased both enthalpy and entropy of the denaturation process.

PMID- 14599590
TI  - Covalent immobilization of chitosan and heparin on PLGA surface.
AB  - Chitosan and heparin were covalently immobilized onto a poly(lactic acid-co
      glycolic acid) (PLGA) surface using N-(3-dimethylaminopropyl)-N'
      ethylcarbodiimide (EDC), N-hydroxysuccinimide (NHS) in a 2-morpholinoethane
      sulfonic acid (MES) buffer system. The properties of the modified PLGA surface
      and the control were investigated by water contact angle measurement and electron
      spectroscopy for chemical analysis (ESCA). The water contact angle of the
      modified film was greatly decreased and the element content on the surface of the
      films changed correspondingly. Platelet adhesion assay showed that blood
      compatibility of the chitosan/heparin modified film was improved while hepatocyte
      culture indicated that the cell compatibility of the modified film was enhanced.

PMID- 14599591
TI  - Catechol 1,2-dioxygenase from Pseudomonas putida in organic media--an electron
      paramagnetic resonance study.
AB  - The ability of an isolated isozyme of catechol 1,2-dioxygenase from Pseudomonas
      putida DSM 437 to function in a non-aqueous environment was investigated. The
      lyophilized enzyme is able to keep its catalytic function catalyzing the
      oxidation of catechol in n-hexane. Electron paramagnetic resonance (EPR)
      spectroscopy at liquid helium temperatures was applied to compare the properties
      of the non-heme iron of the enzyme in the organic solvent and in the aqueous
      solution. The catalytic performance of the enzyme in the organic solvent is
      correlated with the spectroscopic properties of the non-heme iron.

PMID- 14599592
TI  - Three-dimensional models corresponding to the C-terminal domain of human alphaA-
      and alphaB-crystallins based on the crystal structure of the small heat-shock
      protein HSP16.9 from wheat.
AB  - We propose three-dimensional models corresponding to the C-terminal domain of
      human alphaA- and alphaB-crystallins by using the comparative modeling program
      Modeler and the more closely related crystal structure of the small heat-shock
      protein (sHSP) belonging to the eukaryotic species from wheat HSP16.9 as template
      structure. The sequence alignments differ slightly from alignments that were used
      previously to construct alpha-crystallin models based on homology and the crystal
      structure of the more distantly related small heat-shock protein from archaeal
      species; Methanococcus jannaschii Mj HSP16.5, the only related structure then
      available as a template. The alpha-crystallin models based on HSP16.9 show better
      3-D profile scores and reflect the relative shifts in the beta-strands
      corresponding to the beta-sandwich associated with the core C-terminal domain
      that is common to small heat-shock proteins and the alpha-crystallins. The loop
      between the equivalent beta5-beta7 strands corresponds to a region of seven amino
      acid residues deletion in alpha-crystallins and defines the new set of amino acid
      residues likely to be associated with a dimer interface. The models may be useful
      to examine sites of mutations that are known to affect chaperone-like activity
      and provide the structural basis for dimerization in alpha-crystallins.

PMID- 14599593
TI  - Characterization of immunomodulatory polysaccharides from Salvia officinalis L.
AB  - Crude polysaccharide fractions, rich mainly in arabinogalactans (A), pectin (B)
      and glucuronoxylan-related polymers (D), have been obtained from aerial parts of
      sage (Salvia officinalis L.) by sequential extraction with various reagents.
      Arabinogalactans displayed on HPLC a dominance of lower molecular-mass polymers
      (MW < 10,000), while pectin and glucuronoxylan-related polysaccharides showed
      predominance of polymers with MW > 50,000. Individual polysaccharide fractions
      were examined for their immunomodulatory activity in the in vitro comitogenic
      thymocyte test. The polysaccharide fractions tested possessed the capacity to
      induce rat thymocyte proliferation in the order D>B>A. Besides, fraction D
      possessed a significant comitogenic effect, and the SIcomit/SImit ratio 3-4
      indicates potential adjuvant properties of this glucuronoxylan-rich material.

PMID- 14599594
TI  - Irreversible self-assembly of ovalbumin into fibrils and the resulting network
      rheology.
AB  - The self-assembly of ovalbumin into fibrils and resulting network properties were
      investigated at pH 2, as a function of ionic strength. Using transmission
      electron microscopy (TEM), the effect of ovalbumin concentration on the contour
      length was determined. The contour length was increasing with increasing
      ovalbumin concentration. TEM micrographs were made to investigate the effect of
      ionic strength on the contour length. In the measured ionic strength regime (0.01
      0.035 M) fibrils of approximately equal length (+/-200 nm) were observed. TEM
      micrographs showed that the contour length of the fibrils, versus time after
      dilution, remained constant, which indicates that the self-assembly of ovalbumin
      is irreversible. Using the results of rheological measurements, we observed a
      decreasing critical percolation concentration with increasing ionic strength. We
      explain this result in terms of an adjusted random contact model for charged
      semiflexible fibrils. Hereby, this model has now been proven to be valid for
      fibril networks of beta-lg, BSA and, currently, for ovalbumin.

PMID- 14599595
TI  - Mode of action of family 10 and 11 endoxylanases on water-unextractable
      arabinoxylan.
AB  - Microbial endo-beta-1,4-xylanases (EXs, EC 3.2.1.8) belonging to glycanase
      families 10 and 11 differ in their action on water-unextractable arabinoxylan (WU
      AX). WU-AX was incubated with different levels of a Thermoascus aurantiacus
      family 10 and a Sporotrichum thermophile family 11 endoxylanases. At 10 g l(-1)
      arabinoxylan, enzyme concentrations (KE values) needed to obtain half-maximal
      hydrolysis rates (V(max) values) were 4.4 nM for the xylanase from T. aurantiacus
      and 7.1 nM for the xylanase from S. thermophile. Determination of Vmax/KE
      revealed that the family 10 enzyme hydrolysed two times more efficiently WU-AX
      than the family 11 enzyme. Molecular weights of the products formed were assessed
      and separation of feruloyl-oligosaccharides was achieved by anion-exchange and
      size-exclusion chromatography (SEC). The main difference between the feruloylated
      products by xylanases of family 10 and 11 concerned the length of the products
      containing feruloyl-arabinosyl substitution. The xylanase from T. aurantiacus
      liberated from WU-AX a feruloyl arabinoxylodisaccharide (FAX2) as the shortest
      feruloylated fragment in contrast with the enzyme from S. thermophile, which
      liberated a feruloyl arabinoxylotrisaccharide (FAX3). These results indicated
      that different factors govern WU-AX breakdown by the two endoxylanases.

PMID- 14599596
TI  - A biologically active fructan from the roots of Arctium lappa L., var. Herkules.
AB  - From the roots of Arctium lappa L., var. Herkules a low-molecular-weight
      fructofuranan of the inulin-type has been isolated by water extraction and
      ethanol precipitation, followed by ion-exchange chromatography and gel filtration
      of the crude precipitate. The methods employed in structural determination were
      methylation analysis and 1H and 13C NMR spectral measurements. In tests for
      antitussive activity in cats the fructan was found to be equally active as some
      non-narcotic, synthetic preparations used in clinical practice to treat coughing,
      and in mitogenic and comitogenic tests its biological response was comparable to
      that of the commercial Zymosan immunomodulator.

PMID- 14599597
TI  - Catalytic properties and mode of action of three endo-beta-glucanases from
      Talaromyces emersonii on soluble beta-1,4- and beta-1,3;1,4-linked glucans.
AB  - In this paper, we present the first detailed analysis of the modes of action of
      three purified, thermostable endo-beta-D-glucanases (EG V-VII) against a range of
      soluble beta-linked glucans. Studies indicated that EG V-VII, purified to
      homogeneity from a new source, the thermophilic fungus Talaromyces emersonii, are
      strict beta-glucanases that exhibit maximum activity against mixed-link 1,3;1,4
      beta-D-glucans. Time-course hydrolysis studies of 1,4-beta-D-glucan
      (carboxymethylcellulose; CMC), 1,3;1,4-beta-D-glucan from barley (BBG) and
      lichenan confirmed the endo-acting nature of EG V-VII and verified preference for
      1,3;1,4-beta-D-glucan substrates. The results suggest that EG VI and EG VII
      belong to EC 3.2.1.6, as both enzymes also exhibit activity against 1,3-beta
      glucan (laminaran), in contrast to EG V. Although cellobiose, cellotriose and
      glucose were the main glucooligosaccharide products released, the range and
      relative amount of each product was dependent on the particular enzyme, substrate
      and reaction time. Kinetic constants (Km, Vmax, kcat and kcat/Km) determined for
      EG V-VII with BBG as substrate yielded similar Km and Vmax values for EG V and EG
      VI. EG VII exhibited highest affinity for BBG (Km value of 9.1 mg ml(-1)) and the
      highest catalytic efficiency (kcat/Km of 12.63 s(-1) mg(-1) ml).

PMID- 14599598
TI  - The orientation of the alpha-helices in alpha-keratin fibres.
AB  - Considerable physical evidence has been accumulated in support of the polarity of
      alpha-keratin fibres and is summarised here. Dielectric loss and dielectric
      dipole movement in dry intact fibres as they undergo thermal transition above 200
      degrees C show alpha-keratin to be a polar structure. X-ray diffraction has shown
      that this transition corresponds to the randomisation of the organised alpha
      helical structure resulting in the loss of polarity of the fibre. The
      piezoelectric properties of alpha-keratin can only be explained if its alpha
      helical dipoles in the ordered structure alpha-keratin are synergistically
      aligned in the axial direction. If the alpha-helical units of the IFs of alpha
      keratin fibre were in an anti-parallel conformation then dry alpha-keratin would
      show no polarity. FTIR measurements on alpha-keratin fibres extended in water at
      21 and 95 degrees C explain the formation of anti-parallel beta-structures when
      fibres are extended in steam. Contrary to in vitro experimental data there is
      clear evidence that native alpha-keratin fibres are polar structures with the
      alpha-helices aligned in a parallel conformation.

PMID- 14599599
TI  - Mentoring: the VA experience.

PMID- 14599600
TI  - The effect of preoperative biliary stenting on postoperative complications after
      pancreaticoduodenectomy.
AB  - BACKGROUND: Preoperative biliary drainage (PBD) in jaundiced patients undergoing
      pancreaticoduodenectomy remains controversial. METHODS: Patients presenting with
      obstructive jaundice who subsequently underwent pancreaticoduodenectomy from
      January 1996 to June 2002 were included in the study (n = 212). Patients with
      preoperative biliary stents (n = 154) were compared with patients without
      preoperative drainage (n = 58). RESULTS: Patients in the stented group required a
      longer operative time (mean 6.8 hours versus 6.5 hours) and had greater
      intraoperative blood loss (mean 1207 mL versus 1122 mL) compared with the
      unstented group, (P = 0.046 and 0.018). No differences were found with respect to
      operative mortality (2%), incidence of pancreatic fistula (10% versus 14%), or
      intraabdominal abscess (7% versus 5%). Wound infection occurred more often in the
      stented group (8% versus 0%, P = 0.039). CONCLUSIONS: PBD was associated with
      increased operative time, intraoperative blood loss, and incidence of wound
      infection. Although PBD did not increase major postoperative morbidity and
      mortality, it should be used selectively in patients undergoing
      pancreaticoduodenectomy.

PMID- 14599601
TI  - Dysregulation of E-cadherin by oncogenic Ras in intestinal epithelial cells is
      blocked by inhibiting MAP kinase.
AB  - BACKGROUND: Mutations in oncogenic Ras contribute to colorectal tumorigenesis.
      Loss of the cell adhesion protein E-cadherin is associated with tumor invasion
      and metastasis. METHODS: Expression of oncogenic Ras was induced in intestinal
      epithelial cells. Changes in cell morphology, E-cadherin protein expression, and
      E-cadherin localization were examined by light microscopy, Western blot, and
      immunofluorescence respectively. Expression of E-cadherin in human colorectal
      tumors was examined by immunohistochemistry. RESULTS: Induction of oncogenic Ras
      results in an epithelial to mesenchymal transformation with loss of membranous E
      cadherin expression and mis-localization to the cytoplasm. Removal of Ras
      stimulus or blockade of the MAP kinase pathway allowed reversion to a normal
      cellular phenotype and return of E-cadherin to the cell membrane. Loss of or
      decreased expression of E-cadherin was observed in seven of eight colorectal
      tumors. CONCLUSIONS: Oncogenic Ras contributes to malignant transformation and
      altered E-cadherin expression in intestinal epithelial cells. Similar
      dysregulation of E-cadherin is found in human colorectal tumors. Ras effects on E
      cadherin are critical to malignant transformation in our in-vitro model and may
      be an important event in human colorectal tumors.

PMID- 14599602
TI  - Defining the role of the epidermal growth factor receptor in pancreatic cancer
      grown in vitro.
AB  - BACKGROUND: The purpose of this study was to determine the effect of a novel
      epidermal growth factor (EGF) receptor tyrosine kinase inhibitor, Erlotinib, on
      pancreatic cancer cell lines of varying differentiation in vitro. METHODS: Six
      pancreatic cancer cell lines (AsPc-1, CAPAN-1, HPAC, HPAF-II, Mia PaCa-2, PANC-1)
      were grown in the presence of 50 microM or 100 microM of Erlotinib or recombinant
      EGF. Cell proliferation was determined using the MTT assay over 72 hours. The EGF
      receptor gene and protein expression were determined by polymerase chain reaction
      and immunohistochemistry respectively. RESULTS: All cell lines demonstrated the
      presence of the EGF receptor gene and its gene product. Five of six cell lines
      showed significant growth inhibition at 72 hours compared with controls (P
      <0.05). The EGF augmentation increased proliferation of each cell line but this
      increase was only significant in AsPc-1. CONCLUSIONS: Inhibition of EGF receptor
      is a valid therapeutic strategy in pancreatic cancer.

PMID- 14599603
TI  - Which stoma works better for colonic dysmotility in the spinal cord injured
      patient?
AB  - BACKGROUND: The formation of an intestinal stoma is very effective in the
      treatment of colonic dysmotility associated with spinal cord injury (SCI). Little
      is known about the difference in the long-term outcome among left-sided
      colostomies, right-sided colostomies, and ileostomies in this patient population.
      METHODS: The records of 45 SCI patients with intestinal stomas at our institution
      were reviewed retrospectively. Operative details and preoperative colonic transit
      times (CTT) were recorded. Patients who were alive and available were interviewed
      using a questionnaire designed to assess the quality of life (QOL), health
      status, and time to bowel care before and after stoma formation. RESULTS: Between
      1976 and 2002, 45 patients underwent a total of 48 intestinal stomas. A left
      sided colostomy (LC) was formed in 21 patients, right-sided colostomy (RC) in 20,
      and ileostomy (IL) in 7. Three of the patients in the RC group ultimately
      underwent total abdominal colectomy and ileostomy. The indications for stoma
      formation and CTT were different in the three groups. Bloating, constipation,
      chronic abdominal pain, difficulty evacuation with prolonged CTT was the main
      indication in 95% of patients in the RC group, 43% of patients in the LC group,
      and 29% in the IL group. Management of complicated decubitus ulcers, perineal and
      pelvic wounds was the primary indication in 43% of patients in the LC group, 5%
      in the RC group, and none in the IL group. Preoperative total and right CTTs were
      longer in the RC group compared with the LC group: 127.5 versus 83.1 hours (P
      <0.05) and 53.7 versus 28.5 hours (P <0.05), respectively. Eighty-two percent of
      patients (37 of 45) were interviewed at a mean follow-up of 5.5 years after stoma
      formation. Most patients who were interviewed were satisfied with their stoma
      (RC, 88%; LC, 100%; IL, 83%) and the majority would have preferred to have the
      stoma earlier (RC, 63%; LC, 77%; and IL, 63%). The QOL index significantly
      improved in all groups (RC, 49 to 79, P <0.05; LC, 50 to 86, P <0.05; and IL, 60
      to 82, P <0.05), as well as the health status index (RC, 58 to 83, P <0.05; LC,
      63 to 92, P <0.05; IL, 61 to 88, P <0.05). The average daily time to bowel care
      was significantly shortened in all groups (RC, 102 to 11 minutes, P <0.05; LC,
      123 to 18 minutes, P <0.05; and IL, 73 to 13 minutes, P <0.05.). CONCLUSIONS:
      Regardless of the type of stoma, most patients had functional improvement
      postoperatively. Patients who underwent RC had longer CTT and more chronic
      symptoms related to colonic dysmotility, reflecting the preoperative selection
      bias. The successful outcome noted in all groups suggests that preoperative
      symptoms and CTT studies may have been helpful in optimal choice of stoma site
      selection.

PMID- 14599604
TI  - A novel method of peritoneal resuscitation improves organ perfusion after
      hemorrhagic shock.
AB  - BACKGROUND: After resuscitation from hemorrhagic shock, intestinal microvessels
      constrict leading to impairment of blood flow. This occurs despite restoration
      and maintenance of central hemodynamics. Our recent studies have demonstrated
      that topical and continuous exposure of the gut microvasculature to a clinical
      solution (Delflex; Fresenius Medical Care), as a technique of direct peritoneal
      resuscitation (DPR), reverses the postresuscitation vasoconstriction and
      hypoperfusion to a sustained dilation and hyperperfusion. We hypothesize that
      initiation of DPR simultaneously with resuscitation from hemorrhagic shock
      enhance organ blood flow to all tissues surrounding the peritoneal cavity as well
      as distant organs. METHODS: Male Sprague-Dawley rats were anesthetized, intubated
      and cannulated for monitoring of hemodynamics and for withdrawal of blood. Rats
      were hemorrhaged to 50% of mean blood pressure for 60 minutes prior to
      resuscitation with shed blood plus 2 volumes of saline. Animals were randomized
      for intraperitoneal therapy with 30 mL saline (group 1, n = 9), or Delflex (group
      2, n = 9). Whole organ blood flow was measured by colorimetric microsphere
      technique with phantom organ at baseline, after completion of resuscitation, and
      at 120 minutes postresuscitation. Replenishment of the dwelling intraperitoneal
      saline or Delflex was performed in (group 3, n = 8), and (group 4, n = 8),
      respectively at 90 minutes postresuscitation, and a single whole organ blood flow
      was performed at 120 minutes postresuscitation. RESULTS: Direct peritoneal
      resuscitation caused a significant increase in blood flow to the jejunum (35%),
      ileum (33%), spleen (48%), and pancreas (57%), whereas a marked increase in blood
      flow was detected in the lung (111%), psoas major muscle (115%), and diaphragm
      (132%), as compared with the saline treated animals in group 1. At 120 minutes
      postresuscitation, organ blood flow returned to the prehemorrhagic shock baseline
      level in all organs irrespective of peritoneal therapy. Replenishment of the
      intraperitoneal solution in group 3 and 4, enhanced blood flow to the liver,
      kidneys, and diaphragm. CONCLUSIONS: Direct peritoneal resuscitation enhanced
      blood flow to organs incited in the pathogenesis of multiple organ failure that
      follows hemorrhagic shock.

PMID- 14599605
TI  - Major lower extremity amputations at a Veterans Affairs hospital.
AB  - BACKGROUND: This study was made to evaluate the experience at a Department of
      Veterans Affairs (VA) hospital with consecutive major lower extremity amputations
      over a period of 7 years. METHODS: The records of 229 patients (221 male and 8
      female) who underwent 296 consecutive major lower extremity amputations (119
      above-knee amputations [AKA] and 177 below-knee amputations [BKA]) over a period
      of 86 months (September 1994 to October 2001) were retrospectively analyzed. All
      amputations were performed by members of the vascular surgery department.
      RESULTS: Forty of the 229 patients (17%) eventually required a contralateral
      amputation, 27 patients (12%) had BKAs that eventually necessitated conversion to
      AKA, and 44 amputations (15%) required an initial guillotine amputation. The 30
      day mortalities for BKA, AKA, and BKA to AKA operations were 12%, 17%, and 7%,
      respectively. Eighty-eight of the amputations (30%) developed wound
      complications, and required 137 revisions. Seventy-seven of the amputations (26%)
      had undergone prior revascularization, of which 31 (48%) had an early failed
      bypass. The average preoperative ankle/brachial index (ABI) was 0.57. Of the
      patients undergoing amputation, 97 (42%) complained of rest pain, 91 (40%)
      complained of claudication, and 158 (69%) had tissue loss or gangrene at the time
      of their operation. One hundred and forty-six patients (64%) were diabetic.
      Twenty-two patients (9%) were dialysis dependent and 81 patients (35%) admitted
      to smoking. Of the known causes of death, 21 resulted from myocardial infarction,
      22 from congestive heart failure, 14 from respiratory failure, 13 from
      disseminated cancer, 10 from sepsis, 7 from stroke, and 6 from renal failure.
      Preoperative functional status determinations revealed that of 272 patients with
      enough information to assess functional status, 43 were totally dependent, 97
      were partially independent, and 132 were independent. Of the 229 patients, 168
      (73%) were ambulatory prior to their amputation, and at the completion of this
      review only 53 patients (23%) were ambulatory. CONCLUSIONS: Most patients
      undergoing major lower extremity amputations have many comorbidities; hence
      morbidity and mortality rates are high, with the most common causes of death
      being cardiac and respiratory in nature. These data suggest that major lower
      extremity amputations highlight a very high-risk population with only 39%
      survival at 7 years, as well as a costly subset secondary to prolonged
      hospitalization times (average 15 days, range 3 to 105), in addition to the
      extraordinary cost associated with diminished functional status.

PMID- 14599606
TI  - A prospective study of a hand-held ultrasound device in abdominal aortic aneurysm
      evaluation.
AB  - PURPOSE: Effective treatment of abdominal aortic aneurysm (AAA) requires both
      early detection and timely repair to reduce aneurysm-related mortality. The
      purpose of this prospective study was to evaluate the utility of a hand-held
      ultrasonography (US) device in AAA screening in a Veterans Affairs vascular
      surgical service. METHODS: During a 16-month period, patients with risk factors
      for AAA were evaluated in a blinded fashion with a hand-held US device performed
      by physicians. A conventional abdominal duplex US examination was also performed
      by a certified vascular ultrasonographer. Results of the hand-held US was
      compared with the conventional duplex US examination. RESULTS: A total of 104
      patients were evaluated (97 men, mean age 67 +/- 6.3 years). The mean times for
      hand-held and conventional duplex US examinations were 5.3 +/- 3.2 minutes and
      3.1 +/- 2.4 minutes (not significant), respectively. Using the conventional
      duplex US as a reference, the sensitivity and specificity of the hand-held device
      in detecting a AAA were 93% and 97%, respectively. The positive and negative
      predictive values of the hand-held device were 89% and 98%, respectively. The
      likelihood ratios of positive and negative tests of the hand-held US device
      examination were 82 and 0.14, respectively. The diagnostic accuracy of the hand
      held US device as compared with the conventional duplex US was 98%. CONCLUSIONS:
      A hand-held portable US device is effective and accurate in AAA screening with
      results comparable to the conventional abdominal duplex examination. Moreover,
      hand-held portable US for AAA screening can be performed expeditiously during
      physical examination. It should be used as an extension in routine physical
      examination in vascular patients.

PMID- 14599607
TI  - Marked variability of melphalan plasma drug levels during regional hyperthermic
      isolated limb perfusion.
AB  - BACKGROUND: Hyperthermic isolated limb perfusion (HILP) with melphalan as
      treatment for locally recurrent or in-transit malignant melanoma is frequently
      performed but the principle for calculating drug dosage remains poorly
      understood. METHODS: This study examined the pharmacokinetic profile of 14
      consecutive patients to determine what variables were associated with toxicity
      and tumor responses. RESULTS: Marked fourfold variability was noted in patient
      plasma melphalan concentrations. We defined a factor--the ratio of estimated limb
      volume (Vesti) to melphalan volume of distribution (Vss), Vesti/Vss--that was
      much more strongly correlated with acute regional toxicity than either area under
      concentration-time curve or peak plasma concentration. In addition, we found that
      AUX2 was the best correlate of tumor response. CONCLUSIONS: Pharmacokinetic
      evaluation of prospective HILP trials is critical to not only understand response
      and toxicity outcomes but also to potentially improve the therapeutic index of
      regional perfusion.

PMID- 14599608
TI  - Colorectal cancer screening at a Veterans Affairs hospital.
AB  - BACKGROUND: Because of limited resources and common barriers to widespread
      screening, the Surgery Service of the Indianapolis Veterans Affairs Medical
      Center has focused its colorectal screening program on patients undergoing hernia
      repair. Our objective was to examine the success, safety, pathology results, and
      educational benefit of this nontraditional screening program. METHODS: The study
      was a retrospective analysis of a prospectively collected database (1991 to
      2002). Initial screening colonoscopy was performed on 263 average-risk Veterans
      Affairs patients, 217 (83%) in conjunction with hernia repair. Visualized polyps
      were removed or biopsied during colonoscopy and pathology reports for all
      specimens were examined. Results were compared with published screening studies.
      RESULTS: Complete colonoscopy, defined as cecal intubation, was performed in 93%
      of initial screening colonoscopies. There were no major complications, including
      perforation, excessive bleeding, or death, from colonoscopy. Initial colonoscopy
      showed adenomas in 67 patients (25%), hyperplastic polyps in 34 (13%), and
      invasive cancer in 4 (1.5%). Follow-up endoscopies revealed cancer in 2
      additional patients, 3 and 5 years after initial screening. CONCLUSIONS: This
      program is an important training resource for surgical residents. Screening
      colonoscopy performed in conjunction with hernia repair has produced results
      consistent with more conventional methods. The Surgery Service at the
      Indianapolis Veterans Affairs Medical Center is providing colorectal cancer
      screening with a high degree of safety and success in the face of limited
      resources and common barriers to implementation of widespread screening.

PMID- 14599609
TI  - Has the pendulum swung too far in postoperative pain control?
AB  - BACKGROUND: The Joint Commission on Accreditation of Health Care Organizations
      declared pain level to be the "fifth vital sign." This has led to increased
      efforts to reduce patients' pain scores. Current postoperative analgesic
      modalities may not be entirely safe. We prospectively studied pain and sedation
      scores to determine whether postoperative patients were reaching sedation levels
      similar to patients undergoing "conscious sedation" (eg, colonoscopy cases).
      "Conscious sedation" patients have been shown to achieve states of sedation,
      which at time result in oxygen desaturation. METHODS: Fifty-three patients within
      three groups were compared in an observational study. Group 1 included "conscious
      sedation" patients undergoing colonoscopy. Group 2 included postoperative
      patients using patient-controlled analgesia (PCA). Group 3 included postoperative
      patients under nurse-controlled analgesia (NCA). Levels of sedation were
      monitored using the 6-point Ramsay sedation scale. Pain and oxygen saturation
      were monitored using an 11-point verbal scale and finger pulse oximetry,
      respectively. Patients were monitored for up to 12 hours in the postoperative
      period or for the length of their colonoscopy procedure. RESULTS: Patients in
      groups 1 and 2 reached similar sedation levels. CONCLUSIONS: Patients may reach
      dangerous levels of sedation during the first 24 hours postoperatively. Patients
      using PCA devices warrant close observation during this time period.

PMID- 14599610
TI  - Survival and quality of life after organ transplantation in veterans and
      nonveterans.
AB  - BACKGROUND: Some previous studies suggested that transplantation performed in
      Department of Veterans Affairs (VA) patients was associated with a higher rate of
      complications and poorer outcomes. We examined more than a decade of experience
      with solid organ transplantation at a single center and compared VA patients with
      nonveteran patients to assess long-term patient and graft survival and health
      related quality of life (HRQOL). METHODS: Demographic, clinical, and survival
      data were extracted from a database that included all transplants from January
      1990 through December 2002 at Vanderbilt University Medical Center (non-VA) and
      the Nashville VA Medical Center (VA). The HRQOL was assessed in a subset of
      patients using the Karnofsky functional performance (FP) index and the Short-Form
      36 self-report questionnaire. Data were analyzed by Kaplan-Meier survival and
      analysis of variance methods. RESULTS: One thousand eight hundred nine adult
      patients receiving solid organ transplants (1,896 grafts) between 1990 and 2002
      were reviewed: 380 VA patients (141 liver, 54 heart, 183 kidney, 2 lung) and 1429
      non-VA patients (280 liver, 246 heart, 749 kidney, 154 lung). Mean follow-up time
      was 46 +/- 1 months. Five-year graft survival for VA and non-VA patients,
      respectively, was liver 65% +/- 5% versus 69% +/- 3% (P = 0.97); heart 73% +/- 8%
      versus 73% +/- 3% (P = 0.67); and kidney 76% +/- 5% versus 77% +/- 2% (P = 0.84).
      Five-year patient survival was liver 75% +/- 5% versus 78% +/- 3% (P = 0.94);
      heart 73% +/- 8% versus 74% +/- 3% (P = 0.75); and kidney 84% +/- 4% versus 87%
      +/- 2% (P = 0.21) for VA and non-VA, respectively. In the first 3 years after
      transplant, the FP scores for VA versus non-VA patients were 85 +/- 2 versus 87
      +/- 1 (P = 0.50). The SF-36 mental component scales were 47 +/- 3 versus 49 +/- 1
      (P = 0.39); and the SF-36 physical component scales were 37 +/- 2 versus 38 +/- 1
      (P = 0.59), respectively. Longer-term (through year 7) HRQOL scores for VA versus
      non-VA patients were FP 85 +/- 1 versus 88 +/- 1 (P = 0.17); mental component
      scales 47 +/- 2 versus 49 +/- 1 (P = 0.29); and physical component scales 35 +/-
      2 versus 39 +/- 1 (P = 0.05), respectively. CONCLUSIONS: The veteran patients
      have similar graft and patient survival as the nonveteran patients. Overall
      quality of life is similar between veterans and nonveterans during the first
      three years after transplantation. A trend toward a later decline in the
      veterans' perception of their physical functioning may stem from the increased
      prevalence of hepatitis C virus among VA liver transplant recipients, a known
      factor reducing late HRQOL.

PMID- 14599611
TI  - Prognostic factors for the development of gangrenous cholecystitis.
AB  - BACKGROUND: The operative morbidity and mortality for patients with gangrenous
      cholecystitis (GC) remains high. Our objective was to identify preoperative
      prognostic factors for GC in order to distinguish this subset of patients with
      acute cholecystitis (AC). METHODS: From 1/98 to 11/01 the medical records of
      patients who presented with the diagnosis of AC were reviewed. Univariate and
      multivariate analysis were performed on this retrospective data. RESULTS: Of 113
      patients with acute cholecystitis, 45 (39.8%) had histologically confirmed
      gangrenous cholecystitis. Nine variables were identified that were associated
      with GC by univariate analysis: age > or =51 years, African-American race, white
      blood cell count > or =15,000, diabetes, pericholecystic fluid, asparate
      aminotransferase, alanine aminotransferase, alkaline phosphatase, and lipase. Two
      variables were identified by multivariate analysis: diabetes, and white blood
      cell count. CONCLUSIONS: Our data suggest that patients with a history of
      diabetes and white blood cell count >15,000 to be at an increased risk for having
      GC upon presentation and they should have urgent surgical intervention.

PMID- 14599612
TI  - Analysis of Ki-67 antigen expression, DNA proliferative fraction, and survival in
      resected cancer of the pancreas.
AB  - BACKGROUND: Prognostic markers for pancreas cancer, such as CEA, CA19-9, ploidy
      analysis, and S-phase determination using flow cytometry, have not been
      consistently predictive. We chose to evaluate nuclear proliferation, as measured
      by the MIB-1 monoclonal antibody and digital image analysis, as a prognostic
      marker in pancreatic carcinoma, and compare the findings with DNA ploidy and S
      phase analysis. MIB-1 identifies the Ki67 antigen present in nuclei of cells in
      all phases of the cell cycle except G0. METHODS: We retrospectively reviewed 33
      patients with pancreatic adenocarcinoma resected for cure between 1989 and 1994
      with available fixed tissue. Sectioned tissue was stained with MIB-1, and the
      number of positively stained nuclei determined and expressed as a MIB-1 labeling
      index (LI) by quantitative image analysis. Disaggregated nuclei were analyzed by
      flow cytometry using standard techniques. RESULTS: MIB-1 LI for pancreas cancers
      was heterogeneous within and between cancers. The MIB-1 LI for the cancers was 28
      +/- 15 (median 29). There was no correlation between survival and MIB-1
      expression (R(2) = 0.03). Likewise, there was no correlation between MIB-1 LI and
      percentage of cells in S-phase, G(2)/M, or total proliferating cells (S+G(2)/M;
      R(2) = 0.01), nor was there a difference between MIB-1 LI and ploidy (P = 0.88).
      CONCLUSIONS: We conclude that in our patient population, nuclear proliferation in
      pancreatic cancer, as determined by expression of Ki67 nuclear antigen, does not
      appear to correlate with survival and is not a useful prognostic marker. Despite
      intuitive thoughts to the contrary, there is no correlation between cell cycle
      analysis as determined by flow cytometry and Ki67 expression in pancreas cancer.
      Current methods of assessing prognosis after curative resection of cancer of the
      pancreas, including lymph node and margin status, tumor size, and possibly DNA
      ploidy as determined by flow cytometry, are not augmented by the assessment of
      nuclear proliferation by image analysis using the MIB-1 monoclonal antibody.

PMID- 14599613
TI  - A novel model of pneumonia from intraperitoneal injection of bacteria.
AB  - BACKGROUND: Pneumonia remains a major clinical problem in the surgical patient.
      Experimental modeling by intratracheal injection of bacteria is not consistently
      reproducible. In an attempt to produce peritonitis by Klebsiella, we found
      evidence of pneumonia on autopsy and further developed this approach as a new
      experimental model. METHODS: Male Swiss Webster mice were given intraperitoneal
      (IP) injections of Klebsiella pneumoniae serotype 2 in different doses and this
      was compared with similar doses given intravenously (IV). A dose dependent
      survival curve was generated. Subsequently, 10(3) colony forming units (CFU) of
      bacteria were used in further experiments. Blood, peritoneal fluid and lung
      tissue were collected at time points up to 72 hours after injection and were
      cultured for levels of bacteria. Lung weights and myeloperoxidase levels were
      also measured. RESULTS: Intraperitoneal administration of Klebsiella was
      uniformly lethal with as few as 10(2) bacteria. Lung weight increased after IP
      Klebsiella, and all animals became bacteremic within 24 hours correlating with
      high bacterial levels in the lung. Conversely, most animals (72%) survived IV
      injection of bacteria, and were able to clear bacteria from the blood and lung.
      CONCLUSIONS: We found that this model produced no clinically apparent peritonitis
      after 48 hours, but uniformly resulted in histopathologic changes of pneumonia by
      24 hours. Survival time was related to initial dose of Klebsiella and there was a
      linear correlation between bacterial levels in the blood and lung. This model is
      reproducible, simple to perform, and the severity is easy to manipulate.

PMID- 14599615
TI  - Utilization of laparoscopic antireflux surgery at a single Veterans Affairs
      facility compared with the Veterans Affairs national trend.
AB  - BACKGROUND: The widespread use of laparoscopy in the early 1990s has led to an
      increase in the utilization of antireflux procedures for the treatment of
      gastroesophageal reflux disease (GERD). This trend has been observed in the
      private sector, but not within the Department of Veterans Affairs (VA) health
      care system. Published data suggest that among patients undergoing antireflux
      surgical procedures, those in the VA were less likely than those in the private
      sector to undergo laparoscopic surgery. The objective of this study was to
      determine the trend in the use of laparoscopic antireflux surgical procedures at
      our VA facility and compare it with the national VA trend. METHODS: All
      antireflux operations performed at our VA facility from 1991 to 2002 were
      recorded along with techniques used. National VA data on the utilization of
      antireflux procedures from 1991 to 1999 was extracted from a recent publication
      by Finlayson et al. RESULTS: In contrast to the trend observed nationally across
      VA hospitals, the rate of utilization of antireflux surgery at our VA facility
      has increased compared with baseline in 1991. Of 83 fundoplications performed
      from 1991 to 2002, 76 (92%) were attempted or completed laparoscopically. The
      conversion rate from laparoscopic to open approach was 6.6%. CONCLUSIONS: We have
      observed an increase in the utilization of antireflux surgery since 1991 at our
      VA facility. In addition, most fundoplications were performed laparoscopically.
      These findings are in contrast to published national VA data. The presence of
      surgeons with interest in laparoscopy, institutional support, and a dedicated
      esophageal function laboratory may explain these findings.

PMID- 14599614
TI  - 101 laparoscopic splenectomies for the treatment of benign and malignant
      hematologic disorders.
AB  - BACKGROUND: Laparoscopic splenectomy (LS) is the surgical approach of choice for
      patients with hematologic disorders requiring splenectomy. Patients with
      idiopathic thrombocytopenic purpura (ITP) have normal to slightly enlarged
      spleens and benefit the most from LS. METHODS: We reviewed the perioperative
      outcomes in 101 patients who underwent LS between May 1996 and December 2002.
      Patients were divided into three groups--ITP, other benign, and malignant
      hematologic disorders--and compared. RESULTS: The ITP patients (n = 48) had
      significantly smaller spleens and operative times compared with the other groups.
      Splenomegaly in the other benign (n = 23) and malignant hematologic disorders (n
      = 30) groups was responsible for higher open conversion rates and greater need
      for hand-assisted laparoscopic splenectomy (HALS). CONCLUSIONS: Laparoscopic
      splenectomy and HALS can be performed with good results for benign and malignant
      hematologic disorders. The benefits of HALS are similar to LS, so there should be
      a low threshold for HALS in patients with large spleens.

PMID- 14599616
TI  - Can a practicing surgeon detect early lymphedema reliably?
AB  - BACKGROUND: Lymphedema may be identified by simpler circumference changes as
      compared with changes in limb volume. METHODS: Ninety breast cancer patients were
      prospectively enrolled in an academic trial, and seven upper extremity
      circumferences were measured quarterly for 3 years. A 10% volume increase or
      greater than 1 cm increase in arm circumference identified lymphedema with
      verification by a lymphedema specialist. Sensitivity and specificity of several
      different criteria for detecting lymphedema were compared using the academic
      trial as the standard. RESULTS: Thirty-nine cases of lymphedema were identified
      by the academic trial. Using a 10% increase in circumference at two sites as the
      criterion, half the lymphedema cases were detected (sensitivity 37%). When using
      a 10% increase in circumference at any site, 74.4% of cases were detected
      (sensitivity 49%). Detection by a 5% increase in circumference at any site was
      91% sensitive. CONCLUSIONS: An increase of 5% in circumference measurements
      identified the most potential lymphedema cases compared with an academic trial.

PMID- 14599617
TI  - Patterns of disease and surgical treatment among United States veterans more than
      50 years of age with ulcerative colitis.
AB  - BACKGROUND: Ulcerative colitis (UC) is a clinical entity that predominantly
      affects young adults yet large series of middle age or elderly patients with UC
      are infrequently reported. The aim of this study is to identify patterns of
      disease, indications for operation, surgical treatment, and outcome of patients
      more than 50 years of age who required surgery for UC in Department of Veterans
      Affairs (DVA) Medical Centers. METHODS: A population-based study on all patients
      in 159 hospitals of the DVA from 1997 to 2001 was carried out. Data were compiled
      from several national computerized VA data sets. Supplementary information
      including demographic information, discharge summaries, operative reports and
      pathology reports were obtained from local medical records. Patient variables
      were entered into a computerized database and analyzed using the Pearson chi
      square and Fisher's exact tests. Statistical significance is designated as P <
      0.05. RESULTS: One hundred fifty-eight patients were evaluable. The mean age was
      59 years (range 51-81); 99% were male. The mean duration of UC was 23 years
      (range 2 to 50). One hundred of the 158 patients had proctocolitis; 58 had either
      left-sided colitis or proctosigmoiditis. The mean dose of prednisone prior to
      surgery was 20 mg; the mean duration of steroid use was 8 years. The indications
      for elective surgery were intractability (59%), mass or stricture (27%), and
      dysplasia (14%). Twenty of the 158 patients (12%) were operated on emergently for
      either toxic colitis, perforation, or hemorrhage. One hundred three of the 158
      underwent proctocolectomy and permanent ileostomy, 55 underwent a restorative
      proctocolectomy, and underwent a segmental colectomy. Twenty of the 158 patients
      were found to have dysplasia in their colectomy specimens; an additional 10 (7%)
      were found to have invasive cancer. Surgical morbidity was 22%. Overall mortality
      was 4% (7 of 158); all but 1 death occurred after emergent surgery. Mean
      hospitalization was 36 days (range 2 to 297). CONCLUSIONS: Restorative
      proctocolectomy was performed in 36% of veterans more than 50 years of age
      requiring surgery for UC. The majority required surgery for intractable symptoms.
      Dysplasia and invasive cancer was found in 18% of patients. Mortality after
      surgery for acute surgical emergencies remains high.

PMID- 14599619
TI  - Endotoxin potentiates lung injury in cerulein-induced pancreatitis.
AB  - BACKGROUND: In this study we examine the effect of endotoxin (lipopolysaccharide)
      on lung injury in the setting of acute pancreatitis (AP). METHODS: Twelve hourly
      injections of cerulein (50 microg/kg/h) were used to induce pancreatitis in mice.
      Intraperitoneal lipopolysaccharide (LPS [6 mg/kg]) was administered 24 hours
      after the initial cerulein injection. Twenty-four hours after LPS injection,
      myeloperoxidase (MPO) activity, nuclear factor (NF)-kappaB activation, and tumor
      necrosis factor (TNF)-alpha, interleukin (IL)-6, and chemokines MIP-2 and KC
      levels were measured in pancreas, liver, and lung tissues. Four groups of mice
      were studied: cerulein-LPS, cerulein-saline, saline-LPS, and saline-saline
      treated mice. RESULTS: Elevated serum lipase confirmed pancreatitis in cerulein
      treated mice. Lung MPO activity was significantly increased in the cerulein-LPS
      group. NF-kappaB was activated in the liver but not in pancreas and lung tissue.
      Chemokines MIP-2 and KC were elevated in pancreatic tissue only. CONCLUSIONS:
      These findings suggest that gram-negative infections may be an important
      predisposition for the development of adult respiratory distress syndrome in the
      setting of AP and that hepatic NF-kappaB may mediate multisystem injury.

PMID- 14599618
TI  - Adrenomedullin is increased in the portal circulation during chronic sepsis in
      rats.
AB  - BACKGROUND: A clinical hallmark of sepsis is an early, hyperdynamic cardiac phase
      (increased cardiac output) that degrades to a hypodynamic phase, which results in
      poor gut perfusion and subsequent gastrointestinal (GI) hypoxemia, tissue
      ischemia, necrosis and loss of gut barrier function. Studies in rat cecal
      ligation and puncture suggest that the potent vasodilator adrenomedullin (AM)
      might initiate or maintain the hypodynamic phase. We hypothesize that AM
      expression is increased in acute Escherichia coli bacteremia and chronic E coli
      Bacteroides fragilis sepsis. METHODS: Acute bacteremia: male Sprague-Dawley rats
      were anesthetized (urethane/alpha-chloralose), tracheotomized, and cannulated for
      monitoring blood pressure (MABP) and heart rate (HR) and for infusion of E coli
      (10(9) colony-forming units [CFU] E coli per 1 mL normal saline) and blood
      sampling. Arterial blood was withdrawn for arterial blood gas (ABG) measurements
      every 60 minutes. After 6 hours, we harvested lung, liver, kidney, spleen, and
      small intestine tissue samples and drew arterial and portal blood for AM enzyme
      linked immunosorbent assay (ELISA). Chronic sepsis: a sterile gauze pad was
      implanted and animals recovered for 5 days. Twenty-four hours (10(9) CFU E coli
      and 10(9) CFU B fragilis per 1 mL normal saline; 1 injection) or 72 hours (2
      injections) after the inoculation of the back sponge, rats were anesthetized,
      intubated, and cannulated as above. MABP, HR, and ABG were measured for 1 hour
      before tissue and serum harvest for AM ELISA. RESULTS: Sepsis increased HR and
      MABP in all groups. Acute sepsis caused a respiratory alkalosis and pH was also
      elevated in chronic sepsis. Serum AM levels were increased in all groups compared
      with baseline and remained elevated at every time point, but were not different
      between saline controls and septic animals at any time point, except for the
      portal serum from the 72-hour chronic sepsis, which was elevated. CONCLUSIONS:
      These data suggest that surgical manipulation alone is sufficient to stimulate AM
      secretion, most probably from endothelial cells. While the AM levels were
      decreasing at 72 hours compared with 6 hours or 24 hours in the arterial blood
      and the saline control portal blood, it remained elevated in the septic portal
      samples, suggesting that the sepsis-induced increase of AM was derived from the
      gut by a different mechanism than that which elevated arterial serum levels.

PMID- 14599620
TI  - Intravenous methylene blue as an aid to intraoperative localization and removal
      of the adrenal glands during laparoscopic adrenalectomy.
AB  - BACKGROUND: We hypothesized that intravenous methylene blue will facilitate
      adrenal gland identification and resection during laparoscopic adrenalectomy.
      METHODS: Five mini-Hanford pigs were anesthetized and monitored per an approved
      Internal Review Board protocol. Timing of color changes in the adrenals was
      recorded after administering methylene blue at three different doses: 2.5 mg/kg,
      5.0 mg/kg, and 7.5 mg/kg. The time required for laparoscopic adrenalectomy with
      and without methylene blue was recorded. RESULTS: No color change occurred after
      the 2.5 mg/kg dose. For the 7.5 mg/kg versus the 5.0 mg/kg dose there was a more
      rapid bluish color change (mean time, 1.89 minutes versus 3.45 minutes; P = 0.03)
      and a longer duration of bluish color change (mean time, 12.20 minutes versus
      6.19 minutes; P = 0.01). Laparoscopic adrenalectomy using methylene blue resulted
      in a 34.5% faster median resection time (10.13 minutes versus 15.47 minutes).
      CONCLUSIONS: Methylene blue concentrates in the adrenal glands and facilitates
      identification and resection of the adrenal glands by a laparoscopic approach.

PMID- 14599621
TI  - Effects of diabetes and cadaveric organs on functional performance and health
      related quality of life after kidney transplantation.
AB  - BACKGROUND: The current study was undertaken to identify factors specific to
      kidney transplantation that are associated with posttransplant functional
      performance (FP) and health-related quality of life (HRQOL). METHODS: Karnofsky
      FP status was assessed longitudinally in 86 adult kidney transplant recipients.
      Patients reported HRQOL using the Short Form-36 (SF-36) health survey and the
      Psychosocial Adjustment to Illness Scale (PAIS). RESULTS: FP improved (P <0.001)
      after kidney transplantation (from 75 +/- 1 to 77 +/- 1, 81 +/- 1, and 82 +/- 1
      at 0, 3, 6, and 12 months, respectively). Patients receiving organs from living
      donors showed continued improvement through posttransplant year 1 while those
      receiving cadaveric organs stabilized at month 6 (simple interaction contrast,
      year 1 versus pretransplant; P <0.05). Patients receiving dialysis therapy for 6
      months or more prior to transplantation demonstrated lower SF-36 posttransplant
      physical component scores in comparison with patients who were transplanted
      preemptively (38 +/- 1 versus 45 +/- 2, P <0.05). Path analysis demonstrated the
      positive direct effect of time on FP with kidney transplantation (beta = 0.23, P
      <0.05), and the negative direct effects on FP of diabetes (beta = -0.22) and
      cadaveric organs (beta = -0.22, both P <0.05). In turn, FP had a positive direct
      effect on HRQOL (beta = 0.40, P <0.001). CONCLUSIONS: Overall improvement in FP
      is attenuated 1 year after kidney transplantation in recipients of organs from
      cadaveric donors. The positive effect of time after transplantation, and the
      negative effects of cadaveric organs and diabetes on posttransplant HRQOL, are
      indirect and are mediated by the direct effects of these variables on
      posttransplant FP.

PMID- 14599622
TI  - Burn-induced red blood cell deformability and shape changes are modulated by sex
      hormones.
AB  - BACKGROUND: Burns are known to cause changes in red blood cell (RBC)
      deformability and resting shape. However, it is unclear whether sex and sex
      hormones can influence the severity of these alterations. METHODS: Red blood cell
      deformability and shape were examined in proestrus and diestrus female rats,
      ovariectomized female rats, as well as castrated and non-castrated male rats (6
      animals per group) subjected to scald burn. Red blood cell deformability was
      measured by laser ektacytometry and erythrocyte shape was evaluated by scanning
      electron microscopy. RESULTS: Burn-induced RBC deformability changes (decrease in
      elongation index) and shape alterations (increase in the percentage of reversibly
      and irreversibly changed cells) were less severe in proestrus females than in
      diestrus females or males. Ovariectomized rats demonstrated more severe RBC
      changes than non-ovariectomized ones. The degree of RBC damage was the same in
      castrated and non-castrated males. CONCLUSIONS: Removal of female sex hormones
      increases the severity of burn-induced RBC, indicating that female sex hormones
      protect against burn-induced RBC dysfunction. In contrast, male sex hormones do
      not appear to modulate burn-induced RBC dysfunction.

PMID- 14599623
TI  - Caspase activation may be associated with Mycobacterium avium pathogenicity.
AB  - BACKGROUND: Mycobacterium avium causes disseminated infection in
      immunocompromised patients and triggers a process resembling Crohn's disease in
      goats. Colony morphotypes predict pathogenicity. Smooth-transparent (SmT)
      morphotypes are more virulent and induce less interleukin (IL)-1beta and IL-18
      production than avirulent smooth-domed (SmD) morphotypes. Caspases are essential
      for IL-1beta and IL-18 production. METHODS: Caspase activation was examined in
      human monocytes after M. avium infection. RESULTS: Fresh monocytes constitutively
      expressed caspase-1 mRNA and pro-caspase-1. The M. avium infection increased
      monocyte caspase-1 mRNA expression. Furthermore, SmD-infected monocytes expressed
      2.3-fold higher levels (P <0.05, n = 3) of activated caspases than SmT-infected
      monocytes. Caspase-1 inhibition significantly reduced IL-1beta production by SmT-
      and SmD-infected monocytes (P <0.05, n = 4). Caspase-3 inhibition inhibited IL
      1beta production 43.5% +/- 8.0% (P <0.02, n = 4) by SmD-infected but not SmT
      infected monocytes. CONCLUSIONS: Decreased mature IL-1beta release by SmT
      infected monocytes may reflect selective induction of caspase-1 activity but not
      caspase-3. Differential caspase expression in monocytes after infection may
      contribute to M. avium pathogenicity in humans.

PMID- 14599624
TI  - Keyhole limpet hemocyanin, a novel immune stimulant with promising anticancer
      activity in Barrett's esophageal adenocarcinoma.
AB  - BACKGROUND: Keyhole limpet hemocyanin (KLH) is a recently described immune
      stimulant and hapten carrier derived from a circulating glycoprotein of the
      marine mollusk Megathura crenulata. We previously reported that KLH has
      significant antiproliferative effects in vitro against breast, pancreas, and
      prostate cancers. We hypothesized that KLH would be effective against Barrett's
      esophageal adenocarcinoma in an in vitro model. METHODS: Barrett's esophageal
      adenocarcinoma cell lines (SEG-1 and BIC-1) were cultured using standard
      techniques. Cells were plated at 1 x 10(5) and KLH was added at concentrations
      ranging from 400 ng to 100 microg/well. After 24 and 72 h incubation, cells were
      assayed for viability using the MTT technique. Statistical analysis was performed
      using ANOVA. Apoptosis was evaluated using a cell death detection kit after 16
      hours of incubation with KLH. RESULTS: KLH treatment significantly (p < 0.001)
      reduced viability in a dose and time-dependent manner. Apoptosis was increased in
      treated SEG-1 cells, but no changes in apoptosis were seen in treated BIC-1
      cells. CONCLUSIONS: KLH directly inhibits the growth of human Barrett's
      esophageal cancer in vitro by apoptotic and nonapoptotic mechanisms.

PMID- 14599625
TI  - Silyl-heparin adsorption improves the in vivo thromboresistance of carbon-coated
      polytetrafluoroethylene vascular grafts.
AB  - BACKGROUND: Expanded polytetrafluoroethylene (ePTFE) remains the most commonly
      utilized synthetic graft material for infrainguinal arterial reconstruction.
      However, patency rates of ePTFE bypass grafts are inferior to those observed with
      autogenous vein grafts. Modification of the luminal surface of ePTFE grafts such
      as coating with carbon or heparin, may prevent early graft failures and improve
      overall patency rates. We now report our results with a silyl-heparin adsorbed
      carbon-coated ePTFE graft. METHODS: Silyl-heparin was adsorbed onto carbon-coated
      ePTFE vascular grafts (Bard Peripheral Vascular, Tempe, Arizona), which were then
      evaluated for patency and platelet deposition acutely (2 hours after
      implantation) and 7 days after graft implantation in mongrel dogs. Dogs underwent
      bilateral aortoiliac grafting where one heparin adsorbed carbon-coated graft and
      one carbon-coated graft (control) were placed on either (alternating) side.
      Platelet deposition was determined by injection of autologous (111)Indium
      radiolabeled platelets followed by a 2-hour circulation period prior to
      explantation of grafts. Heparin activity of the silyl-heparin grafts (at
      preimplantation and explantation) was determined using an antithrombin-III based
      thrombin binding assay. RESULTS: Graft patency was 100% for both heparin coated
      (5 of 5) grafts and control (5 of 5) grafts in the acute group of dogs. In the 7
      day group, patency was 87.5% for heparin coated (7 of 8) grafts and 50% for
      control (4 of 8) grafts (P = 0.28, Fisher's exact test). Radiolabeled platelet
      studies revealed a significantly lower deposition of platelets on heparin coated
      grafts compared with control grafts in the acute group (17.3 +/- 13.5 versus 35.2
      +/- 17.9 counts per minute, per cm(2) per million platelets, mean +/- SEM; n = 5,
      P <0.05, paired Student t test). In the 7-day group of dogs with bilaterally
      patent grafts (4 of 8), a trend toward a lower deposition of platelets on heparin
      coated grafts compared with control grafts was observed (1.55 +/- 0.409 versus
      2.14 +/- 1.13 counts per minute, per cm(2) per million platelets, mean +/- SEM; n
      = 4, P = 0.52, paired Student t test). Eight percent of the preimplantation
      heparin activity remained on the explanted silyl-heparin grafts after 2 hours and
      only 2% after 7 days. CONCLUSIONS: Silyl-heparin adsorption onto carbon-coated
      ePTFE vascular grafts resulted in improved acute thromboresistance in a canine
      bilateral aortoiliac model. Ongoing laboratory efforts are aimed at improving the
      silyl-heparin retention on vascular grafts. This graft may prove to be useful in
      the clinical setting.

PMID- 14599627
TI  - Cholinergic receptor induction and JNK activation in acute pancreatitis.
AB  - BACKGROUND: Cholecystokinin-A (CCK-A) and cholinergic receptor pathways, capable
      of activating stress kinases p38 mitogen-activated protein kinase (p38(MAPK)) and
      cJUN N-terminal kinase (JNK), are implicated in the pathogenesis of ligation
      induced acute pancreatitis in rats. As ligation-induced acute pancreatitis in
      rats is associated with CCK-A receptor induction and p38(MAPK) activation, and as
      receptor induction could amplify acinar hyperstimulation and exacerbate cell
      stress, we tested the hypothesis that the cholinergic M3 receptor is induced and
      JNK is activated in this model. METHODS: Cholinergic M3 receptor expression and
      JNK activation was compared in rats 1, 3, or 24 hours after sham operation or
      duct ligation. RESULTS: Immunoblot analysis of pancreatic homogenates showed a
      time-dependent increase in cholinergic M3 receptor protein, total JNK, and
      phospho-JNK after duct ligation. CONCLUSIONS: There is a rapid and progressive
      cholinergic M3 receptor induction and JNK activation in ligation-induced acute
      pancreatitis in rats. These findings may have significance in the mechanism of
      disease pathogenesis.

PMID- 14599626
TI  - Altered expression of vascular endothelial growth factor and its receptors in
      normal saphenous vein and in arterialized and stenotic vein grafts.
AB  - BACKGROUND: Myointimal thickening is a major cause saphenous vein graft failure.
      The prominence of medial and adventitial microvessels in stenotic vein grafts and
      the known angiogenic effects of vascular endothelial growth factor (VEGF) lead us
      to investigate the expression of VEGF and its receptors in vein graft
      arterialization and stenosis. METHODS: Normal and arterialized vein graft
      segments were evaluated by reverse transcription-polymerase chain reaction (RT
      PCR) for expression of VEGF-R1 (flt), VEGF-R2 (KDR), and neuropilin-1. The cells
      expressing VEGF, VEGF-R1, VEGF-R2, and neuropilin-1 were identified in normal,
      stenotic, and arterialized vein graft segments by immunohistochemistry. RESULTS:
      Vascular endothelial growth factor, detected in the wall in endothelial cells and
      adventitial microvessels in normal vein, localized to smooth muscle cells,
      endothelial cells and adventitial microvessels in arterialized and stenotic vein.
      VEGF-R1 and VEGF-R2 were expressed infrequently on endothelial cells,
      macrophages, and smooth muscle cells in arterialized and stenotic vein.
      Neuropilin-1 was detected in all specimens. RT-PCR demonstrated significantly
      greater expression of neuropilin-1 in normal vein compared with arterialized vein
      (P <0.05). CONCLUSIONS: The differential expression of VEGF and its receptors in
      normal, arterialized, and stenotic vein grafts suggests that alterations in
      VEGF/VEGF-R2/neuropilin-1 interactions may be important determinants of the
      adaptive response of vein grafts to arterialization.

PMID- 14599628
TI  - Leptin stimulates esophageal adenocarcinoma growth by nonapoptotic mechanisms.
AB  - BACKGROUND: Leptin is a hormone primarily produced by adipocytes and serum leptin
      is elevated in obese persons. One risk factor associated with adenocarcinoma of
      the esophagus is obesity. We hypothesized that leptin would have stimulatory
      effects on esophageal adenocarcinoma and alter apoptosis in vitro. METHODS:
      Barrett's esophageal adenocarcinoma cells (BIC-1 and SEG-1) were cultured with
      human recombinant leptin (80 ng/mL) for 24 hours. Cell growth was determined by
      MTT assay. Apoptosis and necrosis was measured after 16 hours of treatment with
      leptin using a Cell Death Kit. RESULTS: Exogenous leptin stimulated cell
      proliferation in both cell lines. No changes in apoptosis or necrosis resulted
      between control and leptin-treated groups. CONCLUSIONS: We have shown that leptin
      increases the proliferation of human esophageal adenocarcinoma, but does not
      alter cell apoptosis or necrosis. The data suggest that leptin stimulates
      esophageal adenocarcinoma growth by nonapoptotic mechanisms. Leptin antagonism
      may have potential efficacy in esophageal cancer therapy.

PMID- 14599629
TI  - Association between cardiac and noncardiac complications in patients undergoing
      noncardiac surgery: outcomes and effects on length of stay.
AB  - PURPOSE: To determine the relation between cardiac and noncardiac complications
      and their effects on length of stay in patients undergoing noncardiac surgery.
      METHODS: We collected detailed information from the history, physical
      examination, and preoperative tests of 3970 patients aged > or =50 years who were
      undergoing major noncardiac procedures. Serial electrocardiograms and cardiac
      enzyme measurements were performed perioperatively, and cardiac and noncardiac
      complications were recorded prospectively. Multivariate logistic regression
      analysis was used to determine the association between cardiac and noncardiac
      complications, and linear regression was used to assess their effects on length
      of stay. RESULTS: Cardiac complications occurred in 84 patients (2%), and
      noncardiac complications developed in 510 patients (13%). Both types of
      complications occurred in 40 patients (1%). The most common cardiac complications
      were pulmonary edema (n = 42) and myocardial infarction (n = 41). The most common
      noncardiac complications were wound infection (n = 291), confusion (n = 87),
      respiratory failure requiring intubation (n = 62), deep venous thrombosis (n =
      48), and bacterial pneumonia (n = 46). Patients with cardiac complications were
      more likely to suffer a noncardiac complication than were those without cardiac
      complications, even after adjustment for preoperative clinical factors (odds
      ratio = 6.4; 95% confidence interval [CI]: 3.9 to 10.6). Mean length of stay was
      markedly increased in patients who experienced cardiac (11 days; 95% CI: 9 to 12
      days) or noncardiac (11 days; 95% CI: 10 to 12 days) complications, or both (15
      days; 95% CI: 12 to 18 days), as compared with patients without complications (4
      days; 95% CI: 3 to 4 days), even after adjustment for procedure type and clinical
      factors. CONCLUSION: Cardiac and noncardiac complications were strongly linked in
      patients undergoing noncardiac surgery. Patients who experienced one type of
      complication were at increased risk of developing the other type of complication
      as well as prolonged perioperative length of stay.

PMID- 14599630
TI  - The prognostic value of markers of inflammation in patients with troponin T
      negative chest pain before discharge from the emergency department.
AB  - PURPOSE: To assess the prognostic value of markers of inflammation for rule-out
      purposes in patients admitted to the emergency department with troponin T
      negative chest pain. METHODS: Patients presenting to the emergency department
      within 6 hours of symptom onset and who had a normal or nondiagnostic
      electrocardiogram were eligible. The standard rule-out protocol, which included
      serial creatine kinase and creatine kinase-MB measurements, was applied, and
      markers of inflammation (C-reactive protein, erythrocyte sedimentation rate, and
      total white blood cell count and differential count) were measured. The study
      group comprised patients with negative serial troponin T results (<0.06 microg/L)
      who were discharged home after unstable coronary artery disease was ruled out.
      Endpoints during the 6-month follow-up were cardiac death, myocardial infarction,
      or rehospitalization for unstable angina. RESULTS: A total of 382 troponin T
      negative patients were discharged, of whom 2 died, 2 had a myocardial infarction,
      and 7 were rehospitalized for unstable angina. A positive C-reactive protein test
      result (>0.3 mg/dL) was associated with future clinical events (hazard risk [HR]
      = 4.5; 95% confidence interval [CI]: 1.2 to 17.0; P = 0.03), as was a positive
      test (>13 mm/h) for erythrocyte sedimentation rate (HR = 5.6; 95% CI: 1.5 to
      22.2; P = 0.01). Patients with positive results for both tests were at highest
      risk of clinical events (9.3%) compared with patients with other combinations of
      test results (1.1% to 2.1%; HR = 7.5; 95% CI: 2.2 to 25.5; P = 0.001).
      CONCLUSION: The combination of C-reactive protein and erythrocyte sedimentation
      rate had prognostic value in patients with troponin T-negative chest pain and a
      normal or nondiagnostic electrocardiogram in whom unstable coronary artery
      disease was ruled out.

PMID- 14599631
TI  - Inappropriate initial antimicrobial therapy and its effect on survival in a
      clinical trial of immunomodulating therapy for severe sepsis.
AB  - PURPOSE: To examine the effect of inappropriate initial antimicrobial therapy on
      the prognosis of patients with sepsis who were enrolled in a clinical trial of an
      immunomodulating agent conducted in 108 hospitals in North America and Europe.
      METHODS: We assessed initial antimicrobial choice and results of microbiologic
      cultures in 904 patients who had microbiologically confirmed severe sepsis or
      early septic shock. If a patient did not receive at least one antimicrobial agent
      to which the causative microorganisms were susceptible within 24 hours from the
      diagnosis of severe sepsis, then the initial antimicrobial treatment was
      considered to be inappropriate. A propensity score that adjusted for factors
      associated with inappropriate antimicrobial treatment was calculated and included
      in multivariable models to adjust for confounding. RESULTS: A total of 468
      patients (52%) had documented bloodstream infection, and 211 patients (23%)
      received inappropriate initial antimicrobial therapy. Characteristics associated
      with inappropriate treatment were study enrollment in Europe, admission to
      surgery, nosocomial infection, infection with multiresistant microorganisms, and
      fungal or polymicrobial infection (all P <0.05). The 28-day mortality was 24%
      (168/693) for patients in the adequately treated group versus 39% (82/211) for
      patients receiving inappropriate initial antimicrobial therapy (P <0.001). After
      adjusting for comorbid conditions, severity of illness, site of infection, and
      the propensity score, inappropriate antimicrobial therapy was independently
      associated with increased mortality (odds ratio = 1.8; 95% confidence interval:
      1.2 to 2.6). CONCLUSION: In a large cohort of patients with microbiologically
      confirmed severe sepsis, appropriate initial antimicrobial therapy was an
      important determinant of survival. New approaches aimed at improving detection
      and treatment of early sepsis are needed.

PMID- 14599633
TI  - Clostridium difficile infection in patients with unexplained leukocytosis.
AB  - PURPOSE: To determine whether unrecognized Clostridium difficile infection is
      responsible for a substantial proportion of cases of unexplained leukocytosis in
      a tertiary care hospital setting. METHODS: We prospectively identified 60
      patients who had unexplained leukocytosis (white blood cell count > or
      =15,000/mm3). Fecal specimens were tested for C. difficile toxin using an enzyme
      immunosorbent assay. We compared the clinical features of patients who had
      positive or negative assay results, as well as of 26 hospitalized control
      patients who did not have unexplained leukocytosis. RESULTS: Thirty-five (58%) of
      the patients with unexplained leukocytosis had C. difficile toxin in at least one
      fecal specimen as compared with 3 (12%) of the controls (P <0.001). Symptoms of
      colitis were often mild or absent at the time the white blood cell count was
      first elevated or, if present, had not been recognized by the attending
      physicians. Leukocytosis resolved promptly in most patients who were treated with
      metronidazole. In the 25 patients (42%) who had a negative test for C. difficile
      toxin, leukocytosis also tended to resolve during empiric therapy with
      metronidazole; some of these patients may have had C. difficile infection.
      CONCLUSION: The majority of patients in our hospital who had unexplained
      leukocytosis had C. difficile infection. Unexplained leukocytosis in hospitalized
      patients should prompt a search for symptoms and signs consistent with C.
      difficile infection and a study to detect C. difficile. Empiric therapy with
      metronidazole may be effective in the appropriate epidemiologic setting.

PMID- 14599632
TI  - Antihypertensive medication class and pulse pressure in the elderly: analysis
      based on the third National Health and Nutrition Examination Survey.
AB  - BACKGROUND: Widened pulse pressure is an independent predictor of cardiovascular
      outcomes in older persons. The purpose of this study was to examine the
      associations between antihypertensive medication class and the magnitude of pulse
      pressure among persons receiving treatment for hypertension in the third National
      Health and Nutrition Examination Survey. METHODS: We analyzed cross-sectional
      data on 1429 subjects aged 60 years or older who reported receiving one or two
      hypertensive drugs from the following medication classes: beta-blockers,
      diuretics, calcium channel blockers, or angiotensin-converting enzyme inhibitors.
      The sample represented about 9 million people in the noninstitutionalized U.S.
      population. RESULTS: For the sample as a whole, no significant pulse pressure
      difference was found for any medication class when compared with the referent
      beta-blocker group after adjustment for covariates, including mean arterial
      pressure. In a subgroup analysis stratified by median age, mean pulse pressure
      was lower in subjects older than 72 years who used diuretics alone (difference = 
      7 mm Hg, P <0.05) or in combination with beta-blockers (difference = -7 mm Hg, P
      <0.01) than in those who used beta-blockers alone. CONCLUSION: Older hypertensive
      subjects who used diuretics alone or in combination with beta-blockers had lower
      mean pulse pressure as compared with those using beta-blockers alone. These
      findings lend support to recommendations for use of diuretics in older
      hypertensive patients.

PMID- 14599634
TI  - Coronary restenosis: a review of mechanisms and management.
AB  - Percutaneous coronary interventions represent an attractive alternative to
      surgical revascularization; nevertheless, these techniques continue to be
      characterized by their propensity to elicit restenosis. Despite an exhaustive
      search for an effective pharmacotherapy to treat or prevent restenosis, hundreds
      of clinical trials have failed to identify an agent with proven therapeutic
      benefit. Recently, however, the Food and Drug Administration approved
      intracoronary radiation (brachytherapy) as a viable therapeutic option for in
      stent stenosis. In addition, recent randomized trials have shown encouraging
      results for drug-eluting stents. This article reviews the pathophysiology of
      restenosis, along with current and future treatment options.

PMID- 14599635
TI  - Is weight reduction an effective therapy for nonalcoholic fatty liver? A
      systematic review.
AB  - PURPOSE: To assess the evidence supporting the efficacy of weight reduction for
      patients with nonalcoholic fatty liver. METHODS: Potentially relevant studies
      were identified by a computerized search of databases and a manual search of
      abstracts from scientific meetings. Studies were included if they reported
      histology, serum aminotransferase levels, or radiological imaging of the liver in
      obese adult patients who had undergone weight reduction. Weight reduction
      regimens included diet, exercise, antiobesity medications, gastric bypass,
      gastroplasty, or any combination of these interventions. Studies involving
      jejunoileal or small bowel bypass surgery were excluded. RESULTS: We identified
      517 potentially relevant studies, of which 15 met the inclusion criteria: one
      randomized controlled trial (in abstract form), two nonrandomized controlled
      trials, nine case series, one retrospective review, and two case reports. Three
      studies included more than 50 patients, whereas nine studies had 25 or fewer
      patients. Twelve studies used behavioral, dietary, or pharmacologic therapy for
      weight reduction, and three studies used surgical interventions. Although all 15
      studies demonstrated overall improvement in the measurements of liver outcome
      after weight reduction, more than half did not report histologic results.
      CONCLUSION: Despite general acceptance that weight reduction is an effective
      therapy for nonalcoholic fatty liver, this systematic review found little data to
      support or refute this recommendation.

PMID- 14599636
TI  - Clinical gene therapy for nonmalignant disease.
AB  - Gene therapy is envisioned as a potentially definitive treatment for a variety of
      diseases that have a genetic etiology. We reviewed trials of clinical gene
      therapy for nonmalignant, single-gene, and multifactorial disorders and
      infectious diseases, and found limited evidence suggesting that gene therapy may
      benefit patients who have severe, combined, immunodeficiency disorder; cystic
      fibrosis; coronary artery disease or peripheral arterial disease; or hemophilia.
      Effective gene therapy requires the targeted transfer of exogenous genetic
      material into human cells and the subsequent regulated expression of the
      corresponding gene product. Because no phase 3 randomized controlled trials have
      been completed that fulfill these criteria, it is difficult to correlate signs of
      clinical benefit with the administration of gene therapy in any disease.
      Additional clinical and basic research is needed to determine the future role of
      gene therapy.

PMID- 14599638
TI  - Lack of value of the naproxen test in the differential diagnosis of prolonged
      febrile illnesses.

PMID- 14599637
TI  - Vaccinating health care workers against smallpox in an isolated primary care
      facility.

PMID- 14599639
TI  - Cases from the Osler Medical Service at Johns Hopkins University.

PMID- 14599640
TI  - The relation between postoperative cardiac and noncardiac complications:
      pathophysiological dominoes or doubles tennis?

PMID- 14599641
TI  - The importance of appropriate initial antibiotic therapy for hospital-acquired
      infections.

PMID- 14599643
TI  - Evidence of the effectiveness of hawthorn extract.

PMID- 14599644
TI  - Temporary relief of postherpetic neuralgia pain with topical geranium oil.

PMID- 14599645
TI  - Neurological adverse event after administration of the hepatitis A vaccine.

PMID- 14599646
TI  - Reversal of hypereosinophilic syndrome and lymphomatoid papulosis with
      mepolizumab and imatinib.

PMID- 14599647
TI  - Resolution with etanercept of nephrotic syndrome due to renal AA amyloidosis in
      adult Still's disease.

PMID- 14599648
TI  - Tracheal cuff puncture: a complication of percutaneous internal jugular vein
      cannulation.

PMID- 14599649
TI  - Diagnostic yield of bone marrow examination in fever of unknown origin.

PMID- 14599650
TI  - Hematological findings in patients with food-cobalamin malabsorption.

PMID- 14599651
TI  - Pseudomonas aeruginosa urosepsis from use of a hot-water spa.

PMID- 14599652
TI  - Mannitol-induced acute renal failure.

PMID- 14599653
TI  - West Nile virus encephalitis mimicking central nervous system metastases from
      small cell lung cancer.

PMID- 14599654
TI  - Translation of academic discovery into societal benefit: proposal for a balanced
      approach--part 1.

PMID- 14599656
TI  - Temporal computation by synaptic signaling pathways.
AB  - Synaptic signaling comprises a complex molecular network. Such networks carry out
      diverse operations such as molecular logic, signal amplification, memory and
      other aspects of cellular decision-making. The synapse in particular encounters
      complex input patterns that have different temporal sequences. Different input
      patterns to the synapse are known to give rise to a range of synaptic responses,
      including facilitation, depression and various forms of short and long-term
      potentiation. In many cases the stimuli that generate these disparate responses
      are tens of seconds or more in length, much greater than the typical time-courses
      of calcium dynamics. In this paper I propose that the synaptic signaling network
      can perform temporal computation operations such as tuning for stimulus duration
      or interval. Using simulation methods I show that the simple time-courses of
      individual signaling pathways combine in the network to give rise to different
      temporally selective responses. Downstream pathways that exhibit temporal
      integration or amplitude thresholding select different input patterns and thus
      perform temporal computation.

PMID- 14599657
TI  - Role of noradrenergic fibers of the preoptic area in regulating sleep.
AB  - The preoptic area (POA) has noradrenergic (NE) terminals, and this area controls
      sleep apart from body temperature and reproduction. The destruction of
      catecholaminergic (CA) terminals in the POA produced a decrease in sleep in rats.
      This effect was shown to be due to the destruction of NE and not dopaminergic
      terminals. The rats, which were hyperthermic after the destruction of CA fibers
      in the POA, preferred a lower ambient temperature. Though they were unable to
      have normal amount of sleep after lesion, it did not affect their behavioral
      thermoregulation. Acute total sleep deprivation for 48 h led to a significant
      decrease in noradrenaline, increase in the level of metabolites of monoamines,
      and an enhancement in the number of dendritic spines at the medial preoptic area
      (mPOA). Enhanced sleep pressure during sleep deprivation could have led to a
      higher release of noradrenaline, and an increase in dendritic spines in the mPOA.
      Arousal was produced by application of noradrenaline at the mPOA, whereas the
      alpha antagonists produced sleep in free-moving rats. This was in contrast to the
      increased wakefulness produced by the destruction of NE terminals. As wakefulness
      and sleep, respectively, were induced on local application of alpha-2 antagonist
      and agonists, it was suspected that the noradrenaline and alpha antagonists might
      have acted on the alpha-2 receptors, which are predominantly present on the pre
      synaptic terminals. Sleep produced by noradrenaline, which was locally applied at
      the mPOA, after destroying the NE terminals, further confirmed this possibility.
      Hypothermia and sexual arousal produced by application of alpha- and beta
      adrenergic agonists at the mPOA would have contributed towards the wakefulness
      induced by these drugs in normal rats. Thus, the available evidence shows that
      the NE fibers in the POA are involved in the induction of sleep.

PMID- 14599658
TI  - Recent advances in understanding the pathogenesis of polyglutamine diseases:
      involvement of molecular chaperones and ubiquitin-proteasome pathway.
AB  - Polyglutamine diseases consist of a group of familial neurodegenerative disorders
      caused by expression of proteins containing expanded polyglutamine stretch. Over
      the past several years, tremendous progress has been made in identifying the
      molecular mechanisms by which the expanded polyglutamine tract leads to neuronal
      dysfunction and neurodegeneration. A common feature of most polyglutamine
      disorders is the occurrence of ubiquitin-positive neuronal intranuclear
      inclusions. The appearance of ubiquitinated aggregates implies an underline
      incapability of the cellular chaperones and proteasome machinery that normally
      functions to prevent the accumulation of misfolded proteins. Here we review the
      recent studies that have revealed a critical role for molecular chaperones and
      ubiquitin-proteasome pathway in the pathogenesis of polyglutamine diseases.

PMID- 14599659
TI  - 6-Hydroxymelatonin protects against cyanide induced oxidative stress in rat brain
      homogenates.
AB  - Both 6-hydroxymelatonin and N-acetyl-N-formyl-5-methoxykynurenamine are
      photodegradants and enzymatic metabolites of melatonin and are known to retain
      equipotent activity against potassium cyanide-induced superoxide generation
      compared to melatonin. It is not clear whether one or both of these metabolites
      is responsible for this effect. The present study therefore investigates the
      possible manner in which 6-hydroxymelatonin protects against oxidative stress
      induced by cyanide in rat brain homogenates. We examined the ability of 6
      hydroxymelatonin to scavenge KCN-induced superoxide anion generation as well as
      lipid peroxidation. In addition, we also examined the effect of this indole on
      lactate dehydrogenase activity (LDH) as well as mitochondrial electron transport
      using dichlorophenol-indophenol as an electron acceptor. The results of this
      study show that 6-hydroxymelatonin significantly reduces KCN-induced superoxide
      anion generation, which is accompanied by a commensurate reduction in lipid
      peroxidation. Partial reversal of the KCN-induced reduction in mitochondrial
      electron transport is accompanied by a similar reversal of mitochondrial LDH
      activity blunted by KCN. It can thus be proposed that 6-hydroxymelatonin is
      potentially neuroprotective against KCN-induced neurotoxicity.

PMID- 14599660
TI  - Sodium pyruvate protects against H(2)O(2) mediated apoptosis in human
      neuroblastoma cell line-SK-N-MC.
AB  - Free radicals are involved in neuronal damage. The present study was aimed to
      investigate the protective effect of sodium pyruvate-a free radical scavenger
      against hydrogen peroxide (H(2)O(2)) induced apoptosis in human neuroblastoma
      cell line-SK-N-MC. On exposure to H(2)O(2) (0.025 mM) cells exhibited apoptosis
      within 24 h, demonstrating a high caspase 3 activity by 3 h followed by cleavage
      of PARP that was maximum at 24 h. A break down in the mitochondrial membrane
      potential was observed 3 h onwards. Sodium pyruvate protected cells significantly
      (P<0.05) against apoptosis in a dose dependent manner as assessed for cell
      viability by dye exclusion method and apoptosis by TUNEL. Sodium pyruvate
      significantly inhibited caspase 3 activity, cleavage of PARP and breakdown of
      mitochondrial membrane potential. These data suggest that sodium pyruvate
      protects neuronal damage caused by H(2)O(2).

PMID- 14599662
TI  - Role of protein-tyrosine phosphatases on beta-adrenergic receptor mediated
      morphological differentiation of astrocytes.
AB  - A role of protein-tyrosine phosphatases in isoproterenol induced differentiation
      of cultured astrocytes was investigated. Unlike serine/threonine phosphatase
      inhibitors, the tyrosine phosphatase inhibitor, sodium orthovanadate effectively
      blocked transformation of the polygonal astrocytes to process bearing stellate
      cells on exposure to isoproterenol for 2 days. Isoproterenol caused a stimulation
      of c-AMP dependent protein kinase activity in the cells only at the initial
      stages (45 min) and at 12 and 24 h, there was a decline in the level of phospho
      tyrosinated proteins which could be antagonised by the protein kinase A
      inhibitor, H89. Genestein, a protein-tyrosine kinase inhibitor, had no effect on
      the alteration in the morphology of the astroglial cells induced by isoproterenol
      but by itself, decreased the dephosphorylation of the phospho-tyrosinated
      proteins, the decline being less than that observed in isoproterenol treated
      cells. Moreover, unlike H89, genestein had no effect on isoproterenol-induced
      dephosphorylation of phospho-tyrosinated proteins. Taken together it appears that
      the dephosphorylation of tyrosine residues during isoproterenol-induced astrocyte
      differentiation is a downstream event of protein kinase A stimulation and needs
      to attain a critical level in order for the cells to differentiate.

PMID- 14599661
TI  - Calpain inhibitor prevented apoptosis and maintained transcription of proteolipid
      protein and myelin basic protein genes in rat spinal cord injury.
AB  - Spinal cord injury (SCI) is associated with progressive neurodegeneration and
      dysfunction. Multiple cellular and molecular mechanisms are involved in this
      pathogenesis. In particular, the activation of proteases following trauma can
      cause apoptosis in the spinal cord. Calpain, a calcium-dependent cysteine
      protease, plays a major role in apoptosis following trauma. We identified
      apoptosis and decrease in transcription of the genes for proteolipid protein
      (PLP) and myelin basic protein (MBP) in five 1-cm long spinal cord segments (S1,
      distant rostral; S2, near rostral; S3, lesion; S4, near caudal; and S5, distant
      caudal) 24 h after induction of SCI (40 g.cm force) in rats by weight-drop
      method. Sham rats underwent laminectomy and did not receive injury.
      Internucleosomal DNA fragmentation occurred prominently in the lesion (S3),
      moderately in near segments (S2 and S4), and slightly in distant segments (S1 and
      S5) of injured rats, indicating the occurrence of apoptosis in the lesion and
      penumbra. Levels of transcription of PLP and MBP were reduced highly in the
      lesion and moderately in near segments, suggesting that apoptotic loss of cells
      impaired biosynthesis of two important structural components of myelin. Immediate
      administration of the calpain inhibitor E-64-d (1 mg/kg) to injured rats
      prevented apoptosis and restored transcription of these genes, indicating the
      therapeutic efficacy of calpain inhibitor for treatment of SCI.

PMID- 14599663
TI  - Functional characterization of dopaminergic neurons derived from rodent
      mesencephalic progenitor cells.
AB  - Neural progenitor cells existing in the developing and adult brain retain the
      capacity to self renew and to produce the major cell types of the brain opening
      new avenues for restorative therapy of neuropsychiatric disorders. These cells
      can be grown in vitro while retaining the potential to differentiate into nervous
      tissue. A primary target for neurorestoration is Parkinson's disease,
      characterized by a continuous loss of the dopaminergic neurons in the substantia
      nigra pars compacta leading to dopamine depletion in the striatum and subsequent
      clinical symptoms including bradykinesia, rigidity and tremor. We established a
      protocol for long-term expansion and dopaminergic differentiation of rodent and
      human mesencephalic neural progenitor cells. Here we perform functional studies
      using both biochemical and electrophysiological techniques on dopaminergic
      neurons derived from rodent mesencephalic progenitor cells labeled with tyrosine
      hydroxylase (TH) gene promotor-driven expression of enhanced green fluorescence
      protein (EGFP). Thus, we demonstrate that these cells produce and release
      dopamine, express voltage-gated potassium and sodium currents, and fire action
      potentials. Furthermore, we detect a slowly activating hyperpolarization
      activated inward cation current (I(h)), which is specific for dopaminergic
      neurons among present midbrain neurons. Our results demonstrate that
      differentiated mesencephalic progenitors exhibit some major morphological and
      functional characteristics of dopaminergic neurons. Therefore, these neural
      progenitor cells might serve as a useful source of dopaminergic neurons for
      studying the development and degeneration of these cells and may further serve as
      a continuous, on-demand source of cells for therapeutic transplantation in
      Parkinson's disease.

PMID- 14599664
TI  - Protective effect of adenosine in rat model of Parkinson's disease:
      neurobehavioral and neurochemical evidences.
AB  - Normal cellular metabolism produces oxidants which are neutralized within the
      cell by antioxidant enzymes and other antioxidants. An imbalance between oxidant
      and antioxidant has been postulated to lead the degeneration of dopaminergic
      neurons in Parkinson's disease. In this study, we examined whether adenosine, an
      antioxidant, can prevent or slowdown neuronal injury in 6-hydroxydopamine (6
      OHDA) model of Parkinsonism. Rats were treated with adenosine (500, 250, 125
      mg/kg b.wt.) once before surgery and five times after surgery (1 h interval). 2
      microl 6-OHDA (12.5 microg in 0.2% ascorbic acid in normal saline) was infused in
      the right striatum. Two weeks after 6-OHDA infused rats were tested for
      neurobehavioral activity and sacrificed after 3 weeks of 6-OHDA infusion, for the
      estimation of glutathione peroxidase, glutathione-S-transferase, glutathione
      reductase, glutathione content, lipid peroxidation and dopamine and its
      metabolites. Adenosine was found to be successful in up-regulating the
      antioxidant status, lowering the dopamine loss and functional recovery returned
      close to the baseline dose. This study revealed that adenosine, which is an
      essential part of our body, might be helpful in slowing down the progression of
      neurodegeneration in Parkinsonism.

PMID- 14599665
TI  - Properties and prediction of mitochondrial transit peptides from Plasmodium
      falciparum.
AB  - A neural network approach for the prediction of mitochondrial transit peptides
      (mTPs) from the malaria-causing parasite Plasmodium falciparum is presented.
      Nuclear-encoded mitochondrial protein precursors of P. falciparum were analyzed
      by statistical methods, principal component analysis and supervised neural
      networks, and were compared to those of other eukaryotes. A distinct amino acid
      usage pattern has been found in protein encoding regions of P. falciparum:
      glycine, alanine, tryptophan and arginine are under-represented, whereas
      isoleucine, tyrosine, asparagine and lysine are over-represented compared to the
      SwissProt average. Similar patterns were observed in mTPs of P. falciparum. Using
      principal component analysis (PCA), mTPs from P. falciparum were shown to differ
      considerably from those of other organisms. A neural network system (PlasMit) for
      prediction of mTPs in P. falciparum sequences was developed, based on the
      relative amino acid frequency in the first 24 N-terminal amino acids, yielding a
      Matthews correlation coefficient of 0.74 (90% correct prediction) in a 20-fold
      cross-validation study. This system predicted 1177 (22%) mitochondrial genes,
      based on 5334 annotated genes in the P. falciparum genome. A second network with
      the same topology was trained to give more conservative estimate. This more
      stringent network yielded a Matthews correlation coefficient of 0.51 (84% correct
      prediction) in a 10-fold cross-validation study. It predicted 381 (7.1%)
      mitochondrial genes, based on 5334 annotated genes in the P. falciparum genome.

PMID- 14599666
TI  - Ribosomal RNA processing and the role of SmMAK16 in ribosome biogenesis in
      Schistosoma mansoni.
AB  - Ribosome biogenesis is an essential and complex biological process with links to
      cell cycle control, DNA replication and aberrant cell growth. As the process
      becomes better understood at a mechanistic level, new opportunities arise to
      exploit its effects on maturation and fertility, two important targets in
      parasite therapeutics. While the physical structure and sequence of ribosomal RNA
      (rRNA) in the trematode Schistosoma mansoni have been described, the process of
      cleavage, modification and assembly of the mature ribonucleoprotein particles is
      not well characterized. We have investigated the cleavage pathway of rRNA in
      different life cycle stages of the parasite and present evidence supporting a
      proposed model. In addition, we have investigated the role of the S. mansoni
      nucleolar protein SmMAK16 in ribosome biogenesis. Co-immunoprecipitation data and
      polysome analysis support the hypothesis that SmMAK16 associates with pre
      ribosomal precursor complexes. This work represents the first analysis of this
      important and complex process in schistosomes.

PMID- 14599667
TI  - Cloning and analysis of Trypanosoma cruzi lanosterol 14alpha-demethylase.
AB  - Trypanosoma cruzi infection, transmitted by insect vectors or blood transfusions,
      is an important cause of morbidity and mortality in many Latin American
      countries. Treatments are toxic and frequently ineffective in curing patients
      with chronic manifestations of the infection (Chagas disease). Potentially
      exploitable chemotherapeutic targets of T. cruzi are enzymes of the sterol
      biosynthesis pathway. In particular, the P450 enzyme, lanosterol 14alpha
      demethylase, has been implicated as the target of azole antifungal drugs that
      have potent anti-T. cruzi activity. In the work reported here, the T. cruzi
      lanosterol 14alpha-demethylase (Tc14DM) gene was cloned by degenerate PCR. The
      gene was found to be expressed in both insect and mammalian life-cycle stages of
      the parasite. Tc14DM was able to complement the function of the homologous gene
      in yeast (erg11) as demonstrated by restored ergosterol production in an erg11
      deficient yeast strain. When the yeast strain was co-transfected with the P450
      reductase gene from Trypanosoma brucei, the amount of ergosterol production was
      increased, indicating that the endogenous yeast P450 reductase was an inefficient
      partner with Tc14DM. Heterologous expression of Tc14DM in the baculovirus/Sf9
      system resulted in a 52kDa product. The protein was observed to have the
      characteristic absorbance spectra of a P450 enzyme. A typical Type II binding
      spectrum was produced when the imidazole compound, ketoconazole, was mixed with
      the Tc14DM, demonstrating that ketoconazole binds the enzyme.

PMID- 14599668
TI  - Cloning and expression of two secretory acetylcholinesterases from the bovine
      lungworm, Dictyocaulus viviparus.
AB  - We describe the molecular cloning, expression and biochemical characterisation of
      recombinant forms of two secreted acetylcholinesterases from adult Dictyocaulus
      viviparus. The two variants (designated Dv-ACE-1 and Dv-ACE-2) were 613 and 615
      amino acids long and showed 94.7% identity to one another. The highest level of
      identity to other cholinesterases was with ACE-2 of Caenorhabditis elegans. Dv
      ACE-1 and Dv-ACE-2 showed 48.0 and 47.7% identity to C. elegans ACE-2 over 577
      amino acids, respectively. The primary structure of both enzymes showed
      conservation of the catalytic triad and of a tryptophan residue known to be
      critical for the choline-binding site, but differed in the number of potential
      glycosylation sites and at one amino acid in the peripheral anionic site.
      Southern blotting and PCR experiments indicated that the genes encoding these
      enzymes are distinct. When expressed in Pichia pastoris, the enzymes were active,
      but differed subtly in their biochemical characteristics. Both enzymes exhibited
      a preference for acetylcholine as substrate, but differed in the extent of excess
      substrate inhibition and in their optimal pH for activity. The lack of an obvious
      carboxy-terminal membrane anchor and the presence of an insertion at the
      molecular surface were other features which, thus far, appear to be
      characteristic of parasite secreted acetylcholinesterases.

PMID- 14599670
TI  - The mitotic stability of the minichromosomes of Trypanosoma brucei.

PMID- 14599669
TI  - Impaired dimerization and trafficking of ESAG6 lacking a glycosyl
      phosphatidylinositol anchor.

PMID- 14599671
TI  - Leishmania amazonensis Rab7 promotes toxicity of the amino acid ester Leu-OMe in
      amastigote megasomes.

PMID- 14599673
TI  - Construction of adeno-associated virus packaging plasmids and cells that directly
      select for AAV helper functions.
AB  - Recombinant adeno-associated virus type 2 (rAAV) has promise for use as a gene
      therapy vector. Potential problems in the production of rAAV stocks are both the
      limited amount of recombinant virus that is produced by traditional methods and
      the possibility of wild-type replication competent adeno-associated virus (wtAAV)
      contamination. The presence of these contaminants is largely dependent upon the
      helper plasmid used. Whilst wtAAV is not a pathogen, the presence of these
      contaminants is undesirable as they may affect experiments concerning the biology
      of rAAV. Additionally as protocols using rAAV with altered tropism are becoming
      more prevalent, it is important that no recombination be permitted that may cause
      the creation of a replication competent AAV with modified (targeting) capsids.
      Many experimental protocols require the generation of large amounts of high titre
      rAAV stocks. We describe the production of several AAV helper plasmids and cell
      lines designed to achieve this goal. These plasmids possess split AAV rep and cap
      genes to eliminate the production of wtAAV and they possess a selection mechanism
      which is operatively linked to expression from the AAV cap gene. This allows
      positive selection of those cells expressing the highest level of the structural
      capsid proteins and therefore those cells which yield the highest amount of rAAV.

PMID- 14599674
TI  - Virus concentration using polyethyleneimine-conjugated magnetic beads for
      improving the sensitivity of nucleic acid amplification tests.
AB  - To enhance the sensitivity of virus detection by polymerase chain reaction (PCR)
      and reverse-transcriptional (RT)-PCR, we developed a novel virus concentration
      method using polyethyleneimine (PEI)-conjugated magnetic beads. PEI-magnetic
      beads adsorbed efficiently the enveloped viruses Sindbis virus and Herpes simplex
      1 virus, and the nonenveloped virus SV-40, but not the nonenveloped viruses
      porcine parvovirus (PPV) or poliovirus, based on the PCR detection data.
      Furthermore, the infectivity in the supernatant of former viruses was reduced
      markedly after incubation with PEI-magnetic beads. Both real-time PCR and RT-PCR
      revealed that the DNA viruses were concentrated to a maximum of about 100 times
      the expected value, whereas the RNA viruses were concentrated over a thousand
      times, which was significantly more than expected. It was concluded that the PEI
      magnetic beads are a superior novel means of concentrating viruses, with the
      exception of some non-enveloped viruses. The present method was found to enhance
      the sensitivity of virus detection by PCR and RT-PCR.

PMID- 14599675
TI  - Real-time PCR for simultaneous detection and genotyping of bovine viral diarrhea
      virus.
AB  - Since two genotypes of bovine viral diarrhea viruses (BVDV) occur in Belgian
      herds, their differentiation is important for disease surveillance. A
      quantitative real-time PCR assay was developed to detect and classify bovine
      viral diarrhea viruses in genotype I and II. A pair of primers specific for
      highly conserved regions of the 5'UTR and two TaqMan probes were designed. The
      FAM and VIC-labeled probe sequences differed by three nucleotides, allowing the
      differentiation between genotype I and II. The assay detectability of genotype I
      and II real-time PCR assay was 1000 and 100 copies, respectively. Highly
      reproducible data were obtained as the coefficients of variation of threshold
      cycle values in inter-runs were less than 2.2%. The correct classification of
      genotype I and II viruses was assessed by using reference strains and
      characterized field isolates of both genotypes. The application to clinical
      diagnosis was evaluated on pooled blood samples by post run measurement of the
      FAM- and VIC-associated fluorescence. The 100% agreement with the conventional RT
      PCR method confirmed that this new technique could be used for routine detection
      of persistently infected immunotolerant animals.

PMID- 14599676
TI  - Use of acridine orange staining for the detection of rotavirus RNA in
      polyacrylamide gels.
AB  - Acridine orange is a metachromatic intercalator used extensively in
      histochemistry to differentiate double- from single-stranded (ds, ss) nucleic
      acid by the emission of green and red fluorescence, respectively, under
      ultraviolet light. In the present study we standardised a protocol in order to
      use acridine orange to detect rotavirus ds RNA in polyacrylamide gels and
      compared it to silver and ethidium bromide staining. We demonstrated that the
      simplest and best condition was attained when gels containing rotavirus ds RNA
      bands, stained in green, were treated with 4.3 microM acridine orange after
      electrophoresis and destained with distilled water pH 6 at 37 degrees C. Under
      this protocol, rotavirus RNA concentration was calculated and the mean minimum
      amounts of nucleic acid detected by acridine orange, ethidium bromide, and silver
      staining were 26.0 +/- 4.29, 15.6 +/- 1.48 and 1.06 +/- 0.11 ng, respectively.
      The comparison of acridine orange sensitivity with ethidium bromide and silver
      staining, for 25 field strains of rotavirus and one cell-adapted strain (SA11),
      demonstrated concurrent results in 80% of the specimens. Red colour emission
      resulting from the interaction of acridine orange with ss nucleic acid was also
      shown by testing denatured 0.5 kb HindIII digest of lambda phage DNA.
      Furthermore, it was demonstrated that rotavirus ds RNA could be used for reverse
      transcription activity, followed by PCR amplification, after acridine orange
      staining. In conclusion, although acridine orange is less sensitive than ethidium
      bromide and silver staining, its practicality, low cost, metachromatic
      properties, and its non-interference on RT-PCR should be considered. It is
      suggested the use of acridine orange as an appropriate stain for various purposes
      in virology, as well as for the molecular biology of nucleic acid.

PMID- 14599677
TI  - Detection of norovirus (GI, GII), Sapovirus and astrovirus in fecal samples using
      reverse transcription single-round multiplex PCR.
AB  - A reverse transcription (RT) single-round multiplex polymerase chain reaction
      (smPCR) assay was developed to detect simultaneously Norovirus genogroup I and
      II, Sapovirus and astrovirus. A total of 377 diarrhea stool samples (screened for
      rotavirus- and adenorivus-negative) from four regions in Japan during July 2000
      to June 2001 were examined by RT-smPCR. The positive rate was 16.4% (62 out of
      377 stool samples). Norovirus, Sapovirus and astrovirus were detected in 42, 16,
      4 of 60 positive samples, respectively. Coinfection was not found in these
      samples. Infections occurred mainly in November, December and January. The key
      elements of the RT-smPCR are (i) the cDNA synthesis with the Superscript RTII and
      random primer at 42 degrees C for 1 h, at 99 degrees C for 5 min, and (ii) single
      round multiplex PCR by using Taq polymerase mixed together with a mixture of four
      different primer pairs (G1-SKF/G1-SKR for Norovirus genogroup I, COG2F/G2-SKR for
      Norovirus genogroup II, SLV5317/SLV5749 for Sapovirus, PreCAP1/82b for
      astrovirus). All of the four primer pairs amplify the capsid region of target
      viral genome, produce four size-specific amplicons of 330, 387, 434, 719 bp for
      Norovirus genogroup I and II, Sapovirus and astrovirus, respectively. This assay
      provides a more rapid and efficient way to detect these viruses from fecal
      samples in a single test, and also offers the potential for their molecular
      detection in food and environmental samples.

PMID- 14599678
TI  - Activation of dengue protease autocleavage at the NS2B-NS3 junction by
      recombinant NS3 and GST-NS2B fusion proteins.
AB  - Dengue virus possesses a protease complex made up of the non-structural proteins
      NS2B and NS3. This protease complex catalyzes autocleavage (cis) at the junction
      between NS2A and NS2B as well as between NS2B and NS3. It also catalyzes trans
      cleavage at the junctions between NS3 and NS4A as well as NS4B and NS5. The cis
      cleavage at the NS2B-NS3 junction has been demonstrated in Escherichia coli by
      linking a 40-residue hydrophilic segment of NS2B to a NS3 N-terminal protease
      domain carrying the NS2B-NS3 cleavage site. To explore whether the hydrophilic
      segment could be further shortened, residues from both N- and C-termini of the
      NS2B hydrophilic segment were deleted. The results indicate that the four C
      terminal's consecutive Glu residues could be deleted, each one leading to a
      further loss of activity, whereas the N-terminal boundary needed to be absolutely
      preserved. To examine whether an NS2B peptide could be expressed independently
      and added to activate the NS3 protease domain, the hydrophilic region of NS2B was
      fused to the C-terminus of glutathione-S-transferase (GST). This recombinant
      protein was soluble in bacteria and easily purified by affinity chromatography.
      Without removing the GST, the fusion protein activated the NS3 protease domain
      allowing it to function at the adjacent NS2B-NS3 junction. Thus, the findings
      reported below have produced a feasible alternative for the assay of dengue viral
      protease and this should facilitate the development of a screening method for
      inhibitors of dengue protease.

PMID- 14599680
TI  - Comparison of ELISA and RT-PCR for the detection of Prunus necrotic ring spot
      virus and prune dwarf virus in almond (Prunus dulcis).
AB  - A technique based on the reverse transcriptase-polymerase chain reaction (RT-PCR)
      has been developed to detect the presence of Prunus necrotic ringspot virus
      (PNRSV) and prune dwarf virus (PDV) simultaneously in almond. This paper presents
      the results of a 3-year study comparing both enzyme-linked immunosorbent assay
      (ELISA) and RT-PCR for the detection of PNRSV and PDV using 175 almond leaf
      samples. Multiplex RT-PCR was found to be more sensitive than ELISA, especially
      when followed by nested PCR for the detection of PDV. The RT-PCR technique has
      the added advantage that plant material can be tested at any time throughout the
      growing season.

PMID- 14599679
TI  - Development and validation of a real-time PCR assay for the detection and
      quantitation of p53 recombinant adenovirus in clinical samples from patients
      treated with Ad5CMV-p53 (INGN 201).
AB  - The purpose of this study was to assess the usefulness of real-time PCR as a
      quantitative, highly reproducible, and sensitive method, for detecting and
      quantifying p53 recombinant adenovirus in biological samples from cancer patients
      receiving injections of Ad5CMV-p53. The dynamic range of this real-time PCR-based
      assay was wide (at least five orders of magnitude). Our assay used an internal
      positive control in the same PCR tube that is capable of detecting residual PCR
      inhibitors. Serial spiked samples in plasma with known quantities of Ad5CMV-p53
      were evaluated. The minimum detection limit was 2 pfu per PCR (approximately 50
      pfu per ml of plasma) and the quantification values were reproducible. A total of
      2069 controls tested with 1780 plasma samples from 286 patients enrolled in gene
      therapy trials using Ad5CMV-p53 were investigated. Using calibrators to adjust
      the quantitation value, the results confirmed the good performance of the assay.
      In conclusion, the high sensitivity, simplicity and reproducibility of the real
      time Ad5CMV-p53 assay, allowing screening of large numbers of samples, combined
      with its wide dynamic range, make this method particularly suitable for
      monitoring gene therapy trials.

PMID- 14599681
TI  - A modified restriction display PCR method in sample-labelling of DNA microarray.
AB  - The restriction display PCR is a useful technique for studying the diversity of
      gene expression. This method involves ligating the digested genes with adapters
      and amplifying the gene fragments by PCR using universal and selective primers.
      In this study, we improved this restriction display PCR method by using Cy3-UP, a
      fluorescently labelled universal primer, in place of Cy3-dCTP in sample-labelling
      for DNA microarray. The results show that this new method increases significantly
      the sensitivity of the assay, and will have a wide application in the DNA
      microarray field.

PMID- 14599682
TI  - Construction of an infectious chimeric classical swine fever virus containing the
      5'UTR of bovine viral diarrhea virus, and its application as a universal internal
      positive control in real-time RT-PCR.
AB  - RT-PCR is used widely as a diagnostic method to detect and differentiate
      pestiviruses. The construction of two chimeric classical swine fever virus (CSFV)
      recombinants based on a marker virus constructed previously [J. Virol. 72 (1998)
      5318-5322] is described. These viruses, termed vA187CAT_5UTRBVD and
      vA187CAT_IRESBVD, contain the entire 5' untranslated region (5'UTR) or the
      internal ribosome entry site (IRES) of bovine viral diarrhea virus (BVDV),
      respectively. Both chimeric viruses proved to be infectious in cell culture.
      Hence, the 5'UTR as well as the IRES element only of BVDV can substitute for the
      corresponding genome region of CSFV. Next, two sets of primers and corresponding
      dual-labeled TaqMan probes were designed; one detecting specifically a conserved
      but CSFV-specific area within the 5'UTR of wild-type CSFV, the other one
      targeting the CAT gene inserted in vA187CAT_5UTRBVD. The two primer/probe sets
      were combined in a closed-tube multiplex one-step RT-PCR. To monitor the entire
      extraction and detection process limited amounts of vA187CAT_5UTRBVD were added
      directly to clinical samples before RNA extraction. The multiplex RT-PCR proved
      to be as sensitive as the single primer/probe set method, but allowed the
      validation of each sample tested individually, based on the detection of the CAT
      marker gene. vA187CAT_5UTRBVD was also used successfully for foot-and-mouth
      disease virus (FMDV) TaqMan RT-PCR. Therefore, it is considered a universal
      internal positive control for RT-PCR assays to exclude loss of RNA during
      extraction, or failure of amplification due to inhibitory substances present in
      the sample.

PMID- 14599683
TI  - Detection of viral sequences in archival spinal cords from fatal cases of
      poliomyelitis in 1951-1952.
AB  - Poliovirus (PV) subjected to genetic characterization is often isolated from
      faecal carriage. Such virus is not necessarily identical to the virus causing
      paralytic disease since genetic modifications may occur during replication
      outside the nervous system. We have searched for poliovirus genomes in the 14
      fatal cases occurring during the last epidemics in Norway in 1951-1952. A method
      was developed for isolation and analysis of poliovirus RNA from formalin-fixed
      and paraffin-embedded archival tissue. RNA was purified by incubation with Chelex
      100 and heating followed by treatment with the proteinase K and chloroform
      extraction. Viral sequences were amplified by a reverse transcriptase-polymerase
      chain reaction (RT-PCR), the products subjected to TA cloning and sequenced. RNA
      from the beta-actin gene, as a control, was identified in 13 cases, while
      sequences specific for poliovirus were achieved in 11 cases. The sequences from
      the 2C region of poliovirus were rather conserved while those in the 5'
      untranslated region were variable. The developed method should be suitable also
      for other genetic studies of old archival material.

PMID- 14599684
TI  - Evaluation of a line probe assay for identification of hepatitis B virus precore
      variants in serum from chronic hepatitis B carriers.
AB  - A prototype line probe assay (LiPA) for identifying hepatitis B virus (HBV)
      precore variants (INNO-LiPA HBV precore) was evaluated using a panel of 50 sera
      from 46 patients with HBV infection. The assay detected sequence variations
      detected commonly in the precore promoter region and in amino acid codons 28 and
      29 of the precore gene. There was strong agreement between INNO-LiPA HBV precore
      results and those of a codon 28 point mutation assay (PMA), with identical
      results obtained in 40 of 43 sera (93%) typeable by both assays (kappa
      coefficient (kappa)=0.90). In addition, the precore codon 29 sequence identified
      by the INNO-LiPA HBV precore was confirmed by nucleotide sequencing in all seven
      samples analysed. However, the INNO-LiPA HBV precore identified precore promoter
      sequences much less efficiently. The prototype assay could identify codon 28/29
      sequences from as little as 10 HBV genome equivalents in 10 microl serum, and in
      experiments using artificially prepared mixtures of variants could identify a
      minor component constituting 2.5% of the total viral DNA population. The INNO
      LiPA HBV precore was also straightforward technically and rapid, and is therefore
      likely to be useful for epidemiological investigations into the prevalence,
      distribution and clinical significance of HBV precore variants.

PMID- 14599685
TI  - Rapid detection of cucumber vein yellowing virus by tissue-print hybridisation
      with digoxigenin-labelled cDNA probes.
AB  - Hybridisation of tissue prints with nonradioactive cDNA probes was developed to
      detect cucumber vein yellowing virus (CVYV) in cucurbit plants. Results showed
      irregular distribution of the virus within cucumber, zucchini or melon plants
      without defined tropism for a specific tissue. Therefore, reliable diagnosis of
      CVYV requires analysis of tissue prints from at least five different plant sites.
      This detection procedure allows rapid analysis of large numbers of plants and it
      can be useful for epidemiological studies of CVYV and to control virus spread via
      eradication of early foci.

PMID- 14599686
TI  - Mapping of conformational epitopes on capsid protein VP2 of infectious bursal
      disease virus by fd-tet phage display.
AB  - Conformational epitopes on VP2 protein of infectious bursal disease virus (IBDV)
      were mapped using fd-tet phage display. A gene-targeted phage display library was
      made using DNA fragments ranging approximately from 80 to 400 bp of the
      hypervariable region of the VP2 gene of IBDV strain 002-73, as neutralizing
      monoclonal antibodies against the VP2 protein recognize VP2 conformation
      dependent epitopes within the hypervariable region. The phages were selected
      using immobilized monoclonal antibodies. Epitopes on five phages selected with
      monoclonal antibody 17-82 were located between amino acids 211 and 344. A
      constructed phage containing amino acids from 204 to 344 strongly reacted with
      monoclonal antibodies. Compared to that of the constructed phage, the binding of
      monoclonal antibodies to the five selected phages was dramatically reduced when
      several amino acids at either terminus or both termini were absent. The binding
      of a phage, with conversion of the first hydrophilic region into a hydrophobic
      region as a result of a chance frameshift mutation from amino acids 214 to 225,
      dropped sharply. It indicates that conformational epitopes may be up to 423 bp
      long and the commonly suggested fragments of 50-300 bp for making gene-targeted
      phage display libraries are not long enough to cover the conformational epitopes.
      This technique can be used to identify the minimum length of the conformational
      epitopes for developing recombinant vaccines and specific diagnostic tests.

PMID- 14599687
TI  - Rippled-spectrum resolution dependence on level.
AB  - Rippled-density resolution of a rippled sound spectrum (probe band) in both the
      presence and absence of another band (masker) was studied as a function of sound
      level in normal listeners. The resolvable ripple density in the probe band was
      measured by finding the highest ripple density at which an interchange of ripple
      peak and valley positions was detectable (the phase-reversal test). Probe bands
      were 0.5 oct wide with center frequencies of 1, 2, and 4 kHz. In the control
      condition (no masker), the ripple-density resolution was almost independent of
      sound level within a range of 40-90 dB SPL. When an on-frequency masker coincided
      with the probe band (that resulted in reduced ripple depth), resolution decreased
      slightly relative to the control condition but remained little dependent on
      level. With an off-frequency low-side masker, the ripple-density resolution was a
      little less than in the control but almost independent of level within a range of
      40-60 dB SPL and progressively decreased with level increase from 70 to 90 dB
      SPL. The dependence on level was qualitatively similar at all probe frequencies
      and at various widths and positions of the low-side off-frequency masker band.

PMID- 14599688
TI  - Changes in [14C]-2-deoxyglucose uptake in the auditory pathway of hamsters
      previously exposed to intense sound.
AB  - The current study evaluated changes in [14C]-2-deoxyglucose (2-DG) uptake along
      the auditory pathways of hamsters that were exposed unilaterally to intense
      sound. The measurement of the acoustically evoked auditory brainstem responses
      indicated that intense sound exposure caused asymmetrical hearing loss. The 2-DG
      results revealed some changes in metabolic activity in exposed animals, as
      compared to unexposed animals. Significant decreases in 2-DG uptake were found in
      the ipsilateral anteroventral and posteroventral cochlear nucleus, with respect
      to the exposed left ears. Exposed animals also showed significant increases in
      the ipsilateral nucleus of the lateral lemniscus, central nucleus of inferior
      colliculus and medial geniculate body. No significant changes in uptake were
      observed in the ipsilateral dorsal cochlear nucleus, superior olivary complex,
      auditory cortex and any contralateral structures. The mechanisms for the observed
      changes in 2-DG uptake are discussed.

PMID- 14599689
TI  - 3-D reconstruction of the vestibular endorgans in pediatric temporal bones.
AB  - We investigated the vestibular endorgans in three children using 3-D
      reconstructions from histological sections. The right temporal bone of a newborn
      child without peripheral vestibular pathology was used as reference model and the
      temporal bones from a child with Goldenhar syndrome and a child with Pierre Robin
      sequence with known peripheral vestibular pathology were studied. All five
      temporal bones were prepared by the celloidin technique and sectioned at 20
      microm. Each available section was digitized with a slide scanner. The imaging
      data were layered anatomically correctly and rendered in a 3-D software. With
      this technique all vestibular endorgans were reconstructed and measured. The
      standard deviations in distances ranged between 0.5 and 1.2% and in angles
      between 0.1 and 2.9 degrees. Both maculae were curved in the longitudinal and
      transverse axes which described a curve of approximately 35 degrees. The angles
      between the semicircular ducts varied between 97 and 110 degrees. The
      pathological models demonstrated a distorted configuration of the semicircular
      canals and differed substantially from the reference model in most of the
      measured distances and angles. The method presented is capable of generating 3-D
      models of the vestibular system from histological sections with an acceptable
      precision without previously inserted reference marks. Archival celloidin
      sections are widely available and will be an important resource in understanding
      the detailed 3-D geometry of the vestibular system which has not yet been
      accomplished.

PMID- 14599690
TI  - Synaptophysin immunohistochemistry in the human cochlea.
AB  - Light microscopy and immunohistochemical analyses of a freshly prepared human
      cochlea, removed at meningioma skull base surgery, were performed with particular
      emphasis on synaptophysin (SY) reactivity. Synaptophysin, a 38-kDa glycoprotein,
      is one of the most abundant integral membrane proteins of small presynaptic
      vesicles and is a useful marker for sites of synaptic transmission of the
      efferent olivocochlear system in the cochlea. Following fixation and
      decalcification, cryosections of 30 microm were prepared. To introduce
      immunostaining, free-floating sections were exposed to monoclonal SY antibody.
      Positive SY immunostaining was solely restricted to the neural and sensory
      structures and did not include supporting cells of the organ of Corti. Dense
      reaction products were noted around the hair cells, especially at the basal
      portion of the inner and outer hair cells and their neural poles, as well as
      around the inner spiral bundle, tunnel spiral bundle, outer spiral bundle and
      upper tunnel crossing fibers. The majority of spiral ganglion cells stained
      positively. An intermingling network of thin unmyelinated nerve fibers stained
      densely, especially at the basal portions of the cochlea. The spiral limbus,
      inner and outer sulcus cells, basilar membrane, myelinated nerve fibers, spiral
      ligament and the stria vascularis were unstained. Human cochlea obtained during
      surgery offers excellent conditions for immunohistochemical analysis. In the
      basal cochlea in the organ of Corti, outer hair cell area, there may be
      alterations due to noise trauma from the drilling procedure.

PMID- 14599691
TI  - Vestibular evoked myogenic potentials using simultaneous binaural acoustic
      stimulation.
AB  - The aim of this study is to investigate the feasibility of recording vestibular
      evoked myogenic potential (VEMP) using simultaneous binaural acoustic stimulation
      (B-VEMP), and compare it with that using monaural acoustic stimulation (M-VEMP).
      Seven healthy volunteers were evoked by initial B-VEMP test and subsequent M-VEMP
      test, whereas vice versa in another 7 volunteers. All 14 subjects demonstrated
      both B-VEMPs and M-VEMPs, without significant difference in the latencies of p13
      and n23. When using interaural amplitude difference (IAD) ratio for interpreting
      amplitude, B-VEMPs did not differ significantly from that of M-VEMPs. Hence, B
      VEMPs can produce information equivalent to M-VEMPs in terms of response rate,
      latencies, and IAD ratio in healthy subjects. Likewise, similar results were also
      shown in the patients with unilateral Meniere's disease. In conclusion, B-VEMPs
      provide neither different information nor less variability, as compared with M
      VEMPs. In addition, B-VEMPs can offer information on unilateral inner ear
      (saccular) pathology similar to that by M-VEMPs. Furthermore, recording from
      binaural stimulation can be used as a possibly more convenient mode compared with
      two monaural recordings, especially when testing young or old or disabled
      patients, since a continuous muscular effort is required during recording.

PMID- 14599692
TI  - Alterations in the stria vascularis in relation to cisplatin ototoxicity and
      recovery.
AB  - We have investigated whether or not cisplatin-induced depression of the
      endocochlear potential (EP), and its subsequent recovery, possesses a
      morphological correlate in the stria vascularis. Guinea pigs implanted with round
      window electrodes were treated daily with cisplatin (1.5 mg/kg/day) until the
      compound action potential showed a profound hearing loss (> or =40 dB at 8 kHz
      after 5-18 days). Animals were either sacrificed immediately after the shift in
      hearing threshold ('SHORT' group) or allowed to recover for > or =4 weeks and
      subsequently sacrificed ('LONG' group). Control animals ('CONTROL' group) were
      not treated with cisplatin. Using stereological methods we measured the total
      strial cross-sectional area together with the areas occupied by the different
      strial components: the marginal, intermediate and basal cells. The total strial
      cross-sectional area in the basal turn of the LONG group was found to be
      significantly smaller than that of the SHORT and the CONTROL groups, whereas the
      EP was normal in the LONG group (in comparison to the CONTROL group) and markedly
      decreased in the SHORT group. The smaller area in the LONG group was mainly due
      to a decrease in the area occupied by the intermediate cells and to a lesser
      extent to a decrease in the marginal cell area. The area occupied by the basal
      cells did not change. Thus, the marked decrease in EP after 5-18 days of
      cisplatin administration was not related to shrinkage of the stria vascularis.
      Moreover, 4 weeks later the EP showed full recovery, whereas the stria vascularis
      had shrunk markedly.

PMID- 14599693
TI  - Tone burst-evoked myogenic potentials in rat neck extensor and flexor muscles.
AB  - Vestibular evoked myogenic potential (VEMP) has been used to test the
      vestibulocollic reflex. This study establishes a stable recording of VEMPs of
      animals, and presents useful parameters for vestibular ability. In an acute
      experiment, rats were decerebrated, and myogenic potential from neck extensor
      muscles was recorded. The myogenic potentials elicited by a tone-burst stimulus
      showed a biphasic response in the ipsilateral muscle, and the mean latency of the
      response was 3.56 ms, the positive peak appearing at 4.63 ms. The onset latencies
      of the response lengthen as the stimulus becomes weaker; this is the most
      suitable parameter of vestibular ability. The latencies of the monophasic
      response from the spinal cord were shorter than those of muscle. After injection
      of a muscle relaxant, myogenic potentials disappeared immediately, but the spinal
      cord response remained. We succeeded in recording responses not only from acute
      experimental animals but also from free-moving animals for the first time. These
      myogenic potentials were similar to VEMPs in humans; because the threshold of the
      response was higher than the auditory brainstem response threshold by 40-45 dB,
      the response could only be recorded with very high spontaneous muscle activity
      and the latency was shorter than the startle reflex.

PMID- 14599694
TI  - Anatomy of olivocochlear neurons in the hamster studied with FluoroGold.
AB  - The golden hamster (Mesocricetus auratus) is often used in auditory research, but
      little is known about the anatomical organization of its olivocochlear (OC)
      neurons, the source of the efferent innervation of the organ of Corti.
      Accordingly, we labeled the OC neurons projecting to one cochlea by means of
      retrograde axonal transport of FluoroGold. In four animals, all labeled OC
      neurons were counted and digital images of the labeling were captured and
      analyzed morphometrically. In one case, a 3D computer reconstruction of the
      bilateral distribution of OC neurons was made. The largest group of OC neurons
      was comprised by small, intrinsic lateral OC neurons within the ipsilateral
      lateral superior olivary nucleus (LSO), almost all of which (97%) were located
      ipsilaterally. The second largest group consisted of medial OC neurons in the
      ventral nucleus of the trapezoid body, 75% of which were located contralaterally.
      The smallest group consisted of shell neurons surrounding the LSO, 80% of which
      projected ipsilaterally. These three types of neurons are generally similar in
      morphology and distribution to those previously described in the rat and the
      chinchilla. However, there were several unique findings, including the fact that
      the hamster possesses the smallest total number of OC neurons (mean 341) of any
      rodent yet studied.

PMID- 14599695
TI  - Auditory response to intracochlear electric stimuli following furosemide
      treatment.
AB  - The influence of functional hair cells on electrical stimulation of the auditory
      nerve is an important issue as individuals with significant residual hearing are
      now cochlear implant candidates. Previous work has shown that chemical deafening
      during the course of acute experiments changes the auditory nerve's responses to
      electrical stimulation [Third Quarterly Progress Report, NIH contract N01-DC-9
      2106 (2000), Final Report, NIH Contract N01-DC-9-2106 (2002)]. This study
      extended that work by investigating the changes and subsequent recovery following
      furosemide injections which reversibly impair hair-cell function [Hear. Res.
      (1980) 79-89; Hear. Res. 14 (1984) 305-314, J. Physiol. 347 (1984) 685-696; Hear.
      Res. 71 (1993) 202-207]. Acoustic sensitivity of guinea pig subjects was
      repeatedly monitored with the click-evoked compound action potential. Responses
      to single biphasic electric pulses and biphasic electric pulse trains delivered
      by a monopolar intracochlear electrode were also repeatedly assessed using the
      electrically evoked compound action potential (ECAP). Our measures demonstrated a
      clear relationship between the state of hair-cell function and ECAP responses, as
      changes in the latter coincided with the loss or recovery of acoustic
      sensitivity. ECAP growth functions demonstrated increased slope and increased
      maximum (saturation) amplitude. Both trends were reversible and followed
      approximately the time course of post-furosemide hearing recovery. Additional
      changes were observed using electric pulse-train stimulation: (1) the magnitude
      of ECAP amplitude alternation (observed in response to successive stimulus
      pulses) increased, (2) the degree of ECAP adaptation (measured 80-100 ms after
      pulse-train onset) increased, and (3) the degree of refractoriness (measured by
      the ratio of ECAP amplitudes to the second and first pulses) tended to increase.
      All these trends are consistent with the hypothesis that functional hair cells
      desynchronize the population of auditory nerve fibers, thereby changing the
      electrically evoked responses. Viable hair cells may therefore provide positive
      effects on auditory response to electric stimuli delivered to implant patients
      with residual hearing, as they may enhance the random activity of the stimulated
      nerve.

PMID- 14599696
TI  - Late dosing with ethacrynic acid can reduce gentamicin concentration in perilymph
      and protect cochlear hair cells.
AB  - A key factor in the well-known interaction between ethacrynic acid (EA) and
      aminoglycoside antibiotics (AABs) is disruption of the blood-labyrinth barrier
      (BLB), leading to rapid entry of EA and AABs into the cochlear fluids. The idea
      that the blood-labyrinthine fluid concentration gradient might be utilized in a
      protective manner was tested in the current experiment. We hypothesized that
      administering EA when gentamicin (GM) levels are higher in the cochlea than in
      the blood might actually reduce cochlear damage by permitting efflux of GM from
      the cochlear fluids into the bloodstream, down a concentration gradient and
      across a temporarily disrupted BLB. Guinea pigs received 1, 11, 14 or 20
      injections of GM (125 mg/kg i.m.). Approximately half of the animals also
      received a single injection of EA (40 mg/kg i.v.) either concurrently or 12-18 h
      after the last GM injection. Concurrent injection of EA significantly increased
      GM concentration in serum and perilymph at all time points sampled (2.5, 5-8, and
      12 h post injection). Compared to animals that received GM only, animals that
      received a delayed injection of EA had a significantly lower GM concentration in
      perilymph, lower thresholds of the compound action potential, and less outer hair
      cell loss. Collectively, the evidence suggests that EA can reduce GM ototoxicity
      if it is administered 12-18 h after GM, but the mechanism remains to be
      elucidated. The results may have implications for the clinical management of
      aminoglycoside ototoxicity in humans, as well as for understanding the mechanisms
      underlying AAB/EA interactions.

PMID- 14599697
TI  - Real-time quantitative RT-PCR for low-abundance transcripts in the inner ear:
      analysis of neurotrophic factor expression.
AB  - Real-time quantitative reverse transcription-PCR is a highly sensitive technology
      that allows high throughput quantification of gene expression. Application of
      this technique to the inner ear is potentially very important, but is not
      straightforward because tissue harvesting can be challenging, RNA yield from
      individual inner ears is low, and cDNA synthesis from scant RNA can be
      inefficient. To overcome these challenges, we tested many parameters and
      reagents, and developed an approach to reliably quantitate small changes in low
      abundance transcripts. Using this technique we demonstrate the presence and
      quantify amounts of the neurotrophic factors neurotrophin 3 (NT-3), brain-derived
      neurotrophic factor (BDNF) and glial cell-line-derived neurotrophic factor
      (GDNF), in the cochlea and vestibular end organs of postnatal murine inner ear
      (P26). We show that out of the factors tested, BDNF is the only one
      differentially expressed between the cochlea and vestibular end organs, being
      23.4+/-0.3 times more abundant in the vestibular end organs. Within the cochlea,
      GDNF gene expression is 4.9+/-0.2 times greater than NT-3 expression. Within the
      combined vestibular end organs, BDNF expression is 43.0+/-1.5 times greater than
      NT-3 expression. Our results suggest that neurotrophic factors continue to play a
      role in the postnatal inner ear, in addition to their previously shown essential
      role during development.

PMID- 14599698
TI  - Spectral directionality of the external ear of the lesser spear-nosed bat,
      Phyllostomus discolor.
AB  - The directional dependence of sound pressure transformation of head and pinna has
      been measured in the phyllostomid bat Phyllostomus discolor for the frontal
      hemisphere using a maximum length sequence method. The azimuthal position of the
      axis of highest pinna gain came closer to the midsagital plane with increasing
      frequency. The acoustic axis of highest pinna gain was further characterized by
      an increase of the elevation angle with increasing frequency and a specific
      decrease at 55 kHz. Additionally, a spectral notch separated two regions of high
      and low frequency hearing at specific elevation and frequency combinations. The
      special influence of the tragus on the position of the pinna gain axis and the
      spectral notches is demonstrated. The functional implications of the spectral
      notch for hearing in P. discolor are discussed.

PMID- 14599699
TI  - Long-term survival after falls among the elderly in institutional care.
AB  - Falls of the elderly are a major problem in institutional care. However, more
      comprehensive studies concerning the long-time survival of fallen
      institutionalised elderly are lacking. We investigated the 5-year survival of
      institutionalised elderly fallers and controls. Data of the patients aged over 60
      years, who fell during the 1-year period (n=218) in four institutions were
      collected prospectively. The controls consisted of patients of the same age who
      did not fall within the same period (n=632). The survival of both groups was
      analysed by gender in the total data, and in the short-term (ST) and long-term
      (LT) patients separately. In addition, the survival of fallers was investigated
      according to the number of falls per patient. After follow-up, 164 (75%) fallers
      and 369 (58%) controls were dead. The female controls survived best and the
      survival of the male fallers was the poorest. The death rate was higher than
      expected among female fallers and lower than expected among female controls. The
      survival of the patients who fell twice during the 1-year period was clearly
      poorer than of those who fell once or three or more times. No difference in the
      survival rates was found between the injured and non-injured fallers. Falls in
      institutional care predict poor survival. The first and especially the second
      fall should be prevented.

PMID- 14599700
TI  - Predicting falls within the elderly community: comparison of postural sway,
      reaction time, the Berg balance scale and the Activities-specific Balance
      Confidence (ABC) scale for comparing fallers and non-fallers.
AB  - Simple reaction time, the Berg balance scale, the Activities-specific Balance
      Confidence (ABC) scale and postural sway were studied in order to determine cut
      off scores as well as develop a model used in the prevention of fallers within
      the elderly community. One hundred and twenty-five subjects, 45 fallers and 80
      non-fallers were evaluated throughout the study and results indicated that non
      fallers have significantly faster reaction times, have higher scores on the Berg
      balance scale and the ABC scale as well as sway at slower frequencies when
      compared to fallers. Furthermore, all risk factors were subsequently entered into
      a logistic regression analysis and results showed that reaction time, the total
      Berg score and the total ABC score contributed significantly to the prediction of
      falls with 89% sensitivity and 96% specificity. A second logistic regression was
      carried out with the same previous variables as well as all questions of the Berg
      and ABC scales. Results from the logistic analysis revealed that three variables
      were associated with fall status with 91% sensitivity and 97% specificity.
      Results from the following study would seem rather valuable as an assessment tool
      for health care professionals in the identification and monitoring of potential
      fallers within nursing homes and throughout the community.

PMID- 14599701
TI  - Clinical, biochemical and therapeutical aspects of amiodarone-induced
      hypothyroidism (AIH) in geriatric patients with cardiac arrhythmias.
AB  - The clinical features and the laboratory aspects of the amiodarone-induced
      hypothyroidism (AIH) in the elderly as well as the effects of amiodarone
      treatment in aged AIH people have not yet been well clarified. In the present
      paper, we evaluated 18 subjects of both sexes (7 females, 11 males), aged 65-83
      years, affected by AIH, recruited in Central Tuscany, Italy. The patients were
      divided in two subsets on the basis of thyroid stimulating hormone (TSH) values:
      mild (TSH < 20 mU/l; Group A, n=11) and severe (TSH > 20 mU/l; Group B, n=7)
      hypothyroid patients. On the basis of clinical features, hypothyroidism was
      diagnosed only in two patients (out of Group B). Concerning the hormonal pattern,
      we found that free tetraiodothyronine (fT4) levels were significantly lower than
      the normal range only in Group B subjects; TSH and thyroglobulin were higher than
      normal in both groups; free triiodothyronine (fT3) were always in the normal
      range. Thyroid autoantibodies were found positive only in one patient out of
      Group A and in two patients out of Group B. In 5/18 patients T4 substitutive
      therapy was rapidly assigned, because of severe degree of hypothyroidism. In the
      remaining 13/18 patients, we evaluated the clinical behavior of AIH. After
      additional cardiac evaluation, amiodarone was withdrawn in 5/13 patients: during
      follow-up period (4-10 months) four patients became quickly euthyroid while one
      worsened. In 8/13 patients, amiodarone treatment had to be carried on; during
      follow-up (2-48 months), four patients remained mildly hypothyroid, while other
      four patients became severely hypothyroid. In conclusion, in amiodarone treated
      elderly people, diagnosis of hypothyroidism is reliable only on the basis of high
      values of TSH; clinical features and fT3 serum levels never enable diagnosis.

PMID- 14599702
TI  - A screening instrument for a Sicilian neuroepidemiological survey in the elderly.
AB  - We evaluated the sensitivity and specificity of a screening instrument developed
      for use in a two-phase neuroepidemiological survey in Sicily. The Sicilian
      Epidemiological Dementia Study (SEDES) project will evaluate the prevalence and
      incidence of dementia, parkinsonisms and essential tremor in four Sicilian
      municipalities. It is a two-phase door-to-door survey. To identify subjects with
      possible neurological disorders, in this study, we developed a screening
      instrument including a symptoms questionnaire and simple physical tasks for
      parkinsonisms and essential tremor. The Mini-Mental State Examination (MMSE) was
      chosen for screening dementia. The symptoms questionnaire and simple tasks
      developed to identify possible patients with parkinsonism and essential tremor,
      was tested in a hospital setting. To evaluate sensitivity, we selected 20
      patients with essential tremor and 40 with Parkinson's disease (20 with Stages I
      II and 20 with Stages III-V) [Neurology 17 (1967) 427]. To evaluate specificity
      we also selected 20 healthy subjects. The screening instrument was administered
      in a hospital setting by trained interviewers. Sensitivity of the screening
      instrument (questionnaire plus simple tasks) was 100% for essential tremor and
      parkinsonisms regardless of the stage. Specificity of the instrument was 90% (95%
      CI 66.9-98.2); the predictive positive value was 90.9%, while the negative
      predictive value was 100%. Even if validity was assessed in a hospital setting,
      the high sensitivity and specificity obtained suggest that the instrument could
      be an appropriate screening tool for parkinsonisms and essential tremor in a two
      phase neuroepidemiological survey.

PMID- 14599703
TI  - Satisfaction with the care of institutionalized psychogeriatric patients, as
      reflected by a survey of their relatives.
AB  - The patients' satisfaction is an important aspect of quality of care assessment
      in long-term care institutions. However, many psychogeriatric patients are
      institutionalized at an advanced stage of their disease, when they are unable to
      communicate properly and cannot be questioned about their satisfaction with the
      care received in these psychogeriatric settings. Therefore we initiated a survey
      of patients' relatives based on a questionnaire purposely designed, to evaluate
      their satisfaction with the medical, nursing and structural components of the
      institutional care. The relatives of 101 patients, representing 79% of the
      patients in four psychogeriatric wards, responded to the questionnaire. The level
      of satisfaction with the care was high, as reflected by the fact that over 75% of
      the respondents rated the overall question about satisfaction with the medical,
      nursing, and structural components with the maximum of five points. The high
      correlation between the summative and the overall satisfaction supports and even
      strengthens this view. Another finding was the reluctance of most relatives to be
      involved in the personal care of the patients. Our study concluded that the
      relatives do appreciate the efforts of the staff and understand the constraints
      imposed by the nature of the patients' condition. Moreover, both families and
      staff welcomed this study and mentioned its contribution in improving
      communication.

PMID- 14599704
TI  - Dietary intake estimated using different methods in two Italian older
      populations.
AB  - Most of the tools used to assess nutritional intake in large epidemiological
      studies were originally developed to be used in young and middle-aged subjects
      and, therefore, their validity and reliability when employed in older subjects
      remain uncertain. We conducted this study to verify whether the questionnaire
      developed in the context of the European Prospective Investigation into Cancer
      and nutrition (EPIC) could be used to assess dietary intake in the participants
      of InCHIANTI, an epidemiological study of risk factors for disability in late
      life, performed in 633 men (78% aged, > or =65 years) and 802 women (81% aged, >
      or =65 years) randomly sampled from the general population. In particular, the
      aim of this project was to collect preliminary information that could support a
      future study of concurrent validity. Data on food consumption assessed using the
      EPIC questionnaire from the InCHIANTI participants were compared with those
      collected using a 7-day diary in the National Nutritional Investigation into
      Dietary Behavior (INN-CA), a study conducted in 15 Italian centres aimed at
      assessing Italian households' and individuals' dietary intake. In spite of
      different populations and different methods used in data collection, the
      distributions of dietary intake from the two studies were remarkably similar for
      most macro- and micro-nutrients, both in men and women and according to age
      groups. At a population level, a food frequency questionnaire and a costly and
      time-consuming objective method provided similar estimates of dietary intake.
      Future study should attempt to generalize these findings at an individual level
      by collecting data with both instruments in the same subjects.

PMID- 14599705
TI  - Plasma lipid levels in Alzheimer's disease patients treated by Donepezil
      hydrochloride: a cross-sectional study.
AB  - Donepezil hydrochloride is a central acetylcholine esterase inhibitor that is
      widely used in Alzheimer disease (AD). We have recently observed some differences
      in lipid profile between occasional cases of Donepezil hydrochloride users (DU)
      and non-users (DNU). This prompted us to study the levels of plasma lipids in
      these two groups, cross-sectionally. The medical charts of patients with probable
      AD were screened for current use of Donepezil hydrochloride and lipids profile,
      along with other clinical and demographic data. A total number of 105 patients
      were identified and included in the final analysis. Patients were divided into
      two groups (DU and DNU). Plasma levels of lipids were recorded. Mann-Whitney or t
      test for continuous variables and Fisher exact test for categorical variables
      were used to test for significant differences between the groups. Regression
      analysis was applied to identify independently the factors associated with lipid
      levels. Thirty-three patients were DU and 72 DNU. The two groups differed in
      terms of age, lipid levels and cognitive level. DU had statistically significant
      higher levels of triglycerides compared with those not using the drug (P=0.036),
      higher total cholesterol (P<0.001), higher LDL (P=0.001), and higher VLDL
      (P=0.029) levels. DU showed statistically significant high odds ratios for having
      higher cholesterol and triglycerides levels. Multivariate regression analysis
      showed that there are marked differences between DU and DNU with respect to
      plasma lipid profile, also after correcting for age and sex. The higher plasma
      levels of cholesterol and triglycerides may reflect an adverse effect of
      Donepezil hydrochloride. Alternatively, this may indicate that the effect of the
      medication may involve lipid metabolism, rather than other proposed mechanisms.

PMID- 14599706
TI  - Sleep and sleepiness 1 and 9 months after cataract surgery.
AB  - This study was undertaken to analyze sleep development in a group of patients
      during the first 9 months after cataract extraction. Men and women (n=407)
      undergoing cataract surgery at the Department of Ophthalmology, Sundsvall
      Hospital during two periods in 2000-2002 were asked to complete a questionnaire
      on the state and change of sleep and sleepiness 1 and 9 months after the
      operation. The response rate was 90.8%. The mean ages of the participating men
      and women were 74.5 and 75.6 years, respectively. One week after cataract
      extraction the visual acuity in the treated eye was 0.67 (+/-0.31) in men and
      0.69 (+/-0.28) in women (NS), and showed an inverse relationship to age in both
      men (P<0.01) and women (P<0.0001). One month after cataract extraction 28.3% of
      the men and 37.5% of the women experienced poor sleep, and after 9 months the
      figures were 15.8 and 31.4%, respectively. Frequent awakenings and difficulty in
      falling asleep after nocturnal awakenings improved correspondingly. Being well
      rested in the morning increased and daytime sleepiness decreased. The results
      indicate that in elderly persons with cataract sleep is improved 1 month after
      cataract extraction and further improvement during the first 9 months may be
      experienced.

PMID- 14599707
TI  - Correlation between the CAMCOG, the MMSE, and three clock drawing tests in a
      specialized outpatient psychogeriatric service.
AB  - Our objective was to assess the correlation between (1) the Cambridge Cognitive
      Examination (CAMCOG) (including the Mini-Mental State Examination [MMSE]) score
      and three clock drawing tests (CDT) and (2) the three CDTs independently, in a
      specialized outpatient psychogeriatric service. One hundred and fourteen subjects
      completed a comprehensive evaluation and were allocated to one of the following
      groups: dementia of the Alzheimer's type (DAT) in 52; vascular dementia (VD) in
      36; non-dementia (ND; Mood or Anxiety Disorders) in 26. When the entire sample of
      patients is considered, all three CDTs used were highly and significantly
      correlated to the MMSE score, the CAMCOG score, and to each other. In this
      patient population, these cognitive tests may be interchangeable for providing an
      initial objective measure of cognitive function. However, when the same
      correlations were studied in the separate diagnostic groups, in the dementia
      group (DAT and VD) even though the high correlations between the various CDTs
      themselves did not change, the correlations between the MMSE score, the CAMCOG
      score and the CDTs decreased, more evidently in the VD group. This trend became
      even more conspicuous in the ND group, where some of the above mentioned
      correlations became non-significant. We hypothesize that in a real clinical
      situation the clinician initially assumes the role of cognitive "evaluator" (in
      terms of the total sample) followed by the role of cognitive "monitor" (in
      relation to specific diagnostic groups). In the first instance, CDTs, the MMSE,
      and the CAMCOG might be considered interchangeable as an initial objective
      measure of cognitive dysfunction, while in the second role, different CDTs might
      be diversely used, presumably supplemented by other cognitive tests and clinical
      methods.

PMID- 14599708
TI  - Social relations as determinant of onset of disability in aging.
AB  - The purpose of the study was to analyze whether social relations are related to
      onset of disability among old people at 1.5 year follow-up and whether these
      relations vary by age and gender. The study is based on baseline and 1.5 year
      follow-up data on 1396 older non-disabled adults. Social relations were measured
      by questions about diversity in social relations, social participation,
      satisfaction with social relations and instrumental social support. Onset of
      disability was described as developing need of help in at least one of six
      mobility activities. The results showed that a large diversity in social
      relations and high social participation were important factors for maintaining
      functional ability among the 75-year-old men and women, while social support was
      a risk factor for functional decline among the 80-year-old men. The present study
      suggests that being "embedded" in a strong network of social relations provides
      protection against disability by reducing risk of developing disability.

PMID- 14599709
TI  - VIP receptor 1 (VPAC1) promoter targets the expression of a reporter gene to
      cerebellum and adrenal medulla in transgenic mice.
AB  - Vasoactive intestinal peptide (VIP) is a neurotransmitter with neurotropic
      effects. VIP functions through two distinct G-protein-coupled receptor subtypes
      (VPAC1 and VPAC2). We have demonstrated expression of VPAC1 in pediatric nervous
      system tumors, including medulloblastoma arising in the cerebellum and
      neuroblastoma arising in the adrenal medulla. More recently, we have reported the
      differentiation of neuroblastoma cells by upregulation of VIP type 1 receptor
      suggesting a role for VPAC1 in neuronal development. To understand the molecular
      mechanisms regulating VPAC1 expression in both cerebellum and adrenal medulla, we
      have cloned the human VPAC1 gene and sequenced 2.6-kb of the 5'-flanking
      sequence. Expression of the luciferase reporter gene under the control of this
      2.6-kb human VPAC1 promoter was induced 35-fold in a human medulloblastoma cell
      line (DAOY) and 36-fold in a human neuroblastoma cell line (SKNSH). Analysis of
      5'-unidirectional deletion derivatives of the 2.6-kb fragment demonstrated that a
      241-bp sequence immediately upstream of the VPAC1 coding region retains high
      activity, suggesting that it contains the core promoter region. Quantitative RT
      PCR analysis demonstrated that VPAC1 is expressed in mouse cerebellar and adrenal
      tissues. The VPAC1 promoter also directed expression of a reporter gene in
      cerebellum and adrenal medulla in transgenic mice. Along with our previous
      findings, these results suggest that VPAC1 may play a functional role in
      development of both cerebellum and adrenal medulla.

PMID- 14599710
TI  - NPR-C receptors are involved in C-type natriuretic peptide response on bile
      secretion.
AB  - C-type natriuretic peptide (CNP) is a member of the natriuretic peptide family.
      Previous studies reported the presence of natriuretic peptide receptors and mRNA
      CNP in the liver. In the present work, we sought to establish the role of CNP in
      the regulation of bile secretion in the rat and the possible pathways
      involved.CNP diminished basal as well as bile salt-evoked bile flow and bile acid
      output in a dose-dependent manner. It also reduced the excretion of sodium,
      chloride, and potassium but did not modify bile pH or the excretion of
      phospholipids, total proteins, and glutathione. Neither parasympathetic nor
      sympathetic blockade abolished CNP inhibitory response on bile secretion. The
      selective NPR-C agonist, C-ANP-(4-23) amide, diminished bile flow and the co
      administration of both peptides did not further decrease it. CNP did not alter
      mean arterial pressure or portal venous pressure at any given doses.CNP decreased
      bile acid-dependent flow without affecting bile acid-independent flow. The
      inhibitory effect of CNP did not involve the participation of the autonomic
      nervous system or hemodynamic changes. The participation of NPR-C receptors in
      CNP response is strongly supported by present findings. The present study shows
      that CNP modulates bile secretion in the rat, suggesting that CNP may be part of
      the large family of peptides involved in the regulation of gastrointestinal
      physiology.

PMID- 14599711
TI  - Peripheral administration of GLP-2 to humans has no effect on gastric emptying or
      satiety.
AB  - Glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2) are secreted
      in parallel to the circulation after a meal. Intravenous (IV) GLP-1 has an
      inhibitory effect on gastric emptying, hunger and food intake in man. In rodents,
      central administration of GLP-2 increases satiety similar to GLP-1. The aim of
      the present study was to assess the effect of IV administered GLP-2 on gastric
      emptying and feelings of hunger in human volunteers. In eight (five men) healthy
      subjects (age 31.1+/-2.9 years and BMI 24.1+/-1.0 kg m(-2)), scintigraphic solid
      gastric emptying, hunger ratings (VAS) and plasma concentrations of GLP-2 were
      studied during infusion of saline or GLP-2 (0.75 and 2.25 pmol kg(-1) min(-1))
      for a total of 180 min. Concentrations of GLP-2 were elevated to a maximum of 50
      and 110 pmol l(-1) for 0.75 and 2.25 pmol kg(-1) min(-1) infusion of GLP-2,
      respectively. There was no effect of GLP-2 on either the lag phase (29.5+/-4.4,
      26.0+/-5.2 and 21.2+/-3.6 min for saline, GLP-2 0.75 or 2.25 pmol kg(-1) min(-1),
      respectively) or the half emptying time (84.5+/-6.1, 89.5+/-17.8 and 85.0+/-7.0
      min for saline, GLP-2 0.75 or 2.25 pmol kg(-1) min(-1), respectively). The change
      in hunger rating after the meal to 180 min was also unaffected by infusion of GLP
      2. GLP-2 does not seem to mediate the ileal brake mechanism.

PMID- 14599712
TI  - The effect of chronic CRF1 receptor blockade on the central CCK systems of Fawn
      Hooded rats.
AB  - Corticotropin-releasing factor (CRF) is a neuropeptide associated with the
      integration of physiological and behavioural responses to stress. More recently,
      the CRF system has been implicated in the modulation of affective state and in
      the actions of abused drugs, including ethanol. As such, we have previously
      demonstrated that the selective, centrally acting CRF(1) receptor antagonist
      antalarmin displays an acute anxiolytic action and reduces established volitional
      ethanol consumption in isolation-reared Fawn-Hooded rats [Neuroscience 117 (2003)
      243]. Similar to CRF, CCK is a neuropeptide found in high abundance throughout
      the neuraxis and is involved in the control of appetite, anxiety, reward and
      hormone regulation. Given the similar functions regulated by the neuropeptides
      CRF and CCK, it is of importance to determine whether interactions exist between
      these neuropeptides. Therefore, the aim of the present study was to examine the
      effects of chronic CRF(1) receptor blockade on the central CCK systems of Fawn
      Hooded (FH) rats. Thus, bi-daily antalarmin treatment (20 mg/kg ip) induced a
      significant increase in CCK-B receptor-binding density throughout the neuraxis,
      indicative of either a global increase in receptor number or an increase in
      receptor affinity. In contrast, chronic antalarmin treatment resulted in
      bidirectional, region-specific changes in preproCCK messenger ribonucleic acid
      (mRNA) expression. Interestingly, this effect on CCK mRNA expression was
      restricted to the thalamocortico-limbic system, which is intimately involved in
      the integration of emotive behaviour and central reward processing. Therefore,
      these data provide clear evidence of the ability of chronic CRF(1) receptor
      blockade to significantly influence the central CCK systems of the rat.

PMID- 14599713
TI  - Inhibitory effect of galanin on dopamine induced increased oxytocin secretion in
      rat neurohypophyseal tissue cultures.
AB  - The regulation of oxytocin (OT) release by galanin (GAL) at the neurohypophyseal
      (NH) nerve terminal is not adequately understood. The effect of GAL on the
      secretion of OT was studied in 13- to 14-day cultures of isolated rat NH tissue.
      By this time, the hormone content of the medium had become constant. The OT
      content of the supernatant medium was determined by RIA after a 1- or 2-h
      incubation. A significantly decreased content of OT was found following
      incubation with 10(-6)-10(-8) M doses of GAL. Dopamine (DA) and the DA-active
      drugs apomorphine (APM) and Pro-Lys-Gly (PLG) (10(-6) M in each medium) increased
      the OT synthesis of NH tissue cultures. This elevation of OT secretion could be
      blocked by the administration of GAL together with DA, APM or PLG. The DA
      blocking effect of GAL was prevented by previous treatment with the GAL receptor
      antagonist galantid (M15). The results indicate that OT release from the NH is
      directly influenced by the GAL-ergic system. The GAL-ergic control of OT
      secretion from NH tissue in rats can occur at the level of the posterior
      pituitary.

PMID- 14599714
TI  - Role of Ca2+ in the secretory and biosynthetic response of porcine gonadotropes
      to substance P and gonadotropin-releasing hormone.
AB  - Substance P has been previously shown to stimulate luteinizing hormone (LH)
      secretion and synergistically enhance gonadotropin-releasing hormone (GnRH)
      evoked LH release from cultured pig pituitary cells. To investigate the
      mechanisms involved in these responses, the effects of substance P (100 nM; 4 h)
      and/or GnRH (10 nM, 4 h) on LH release, LH intracellular content, and betaLH mRNA
      accumulation were evaluated in the absence or presence of extracellular Ca(2+).
      Likewise, the effects of substance P on the dynamics of cytosolic free Ca(2+)
      concentration ([Ca(2+)](i)) were examined in single cells. Extracellular Ca(2+)
      deprivation abolished both substance P- and GnRH-stimulated LH release, as well
      as their synergistic interaction. The substance P antagonist D-Arg1,D-Phe5,
      Trp7,9,Leu11-substance P (100 nM) blocked the stimulatory effect of substance P
      on LH release and its interaction with GnRH without affecting GnRH-induced LH
      secretion. Whereas substance P did not modify betaLH transcript levels, GnRH
      stimulated betaLH mRNA accumulation through a mechanism dependent upon
      extracellular Ca(2+). Substance P directly increased [Ca(2+)](i) in a 30% of
      gonadotropes by causing two distinct types of response kinetics with single-peak
      (predominant, 83.3%) or sustained-plateau profiles. Reduction of external
      [Ca(2+)] decreased by half the percent of responsive cells, which only showed
      single-peak profiles. Taken together, our results demonstrate that the ability of
      substance P to stimulate basal and GnRH-induced LH release is exerted directly
      upon gonadotropes, is extracellular Ca(2+)-dependent and does not seem to require
      net increases in betaLH mRNA levels. Moreover, [Ca(2+)](i) measurements revealed
      that although substance P action in pig gonadotropes is strongly dependent on
      extracellular Ca(2+) influx, it would also involve intracellular Ca(2+)
      mobilization. Finally, extracellular Ca(2+) also plays a requisite role to
      sustain GnRH-stimulated increases in both betaLH mRNA and LH release.

PMID- 14599715
TI  - The therapeutic effect of recombinant human trefoil factor 3 on hypoxia-induced
      necrotizing enterocolitis in immature rat.
AB  - Trefoil peptides are a new class of regulatory peptides involved in mucosal
      protection and repair in the gastrointestinal tract. Among them, trefoil factor 3
      (TFF3) (intestinal trefoil factor) is known to be cytoprotective in the gut. The
      aim of this study was to determine the effect of recombinant human trefoil factor
      3 (rhTFF3) on hypoxia-induced necrotizing enterocolitis (NEC) in immature rats.
      In the present study, thirty-two 1-day-old Wistar rat pups were randomly divided
      into four groups. Group 1 served as nonhypoxic controls. Group 2 rats were
      subjected to hypoxia reoxygenation (H/O) and then were returned to their mothers.
      Groups 3 and 4 rats were subjected to H/O, were returned to their mothers, and
      were treated with rhTFF3 intraperitoneally (0.5 mg) and subcutaneously (0.2 mg),
      respectively, for the next 3 days. All animals were killed on day 4, and
      intestine specimens were obtained to determine the histological changes, tissue
      level of interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha),
      malondialdehyde (MDA), prostaglandin E2 (PGE2), tromboxane B2 (TXB2), and nitric
      oxide (NO). In addition, the effects of rhTFF3 on abundance of inducible nitric
      oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) were also investigated. In
      neonatal NEC (group 2), necrosis of villi and crypts and, in some cases,
      transmural necrosis was observed under light microscopy. Tissue level of
      interleukin-8, tumor necrosis factor-alpha, malondialdehyde, prostaglandin E2,
      tromboxane B2, and nitric oxide were significantly higher than group 1. In
      addition, abundance of inducible nitric oxide synthase and cyclooxygenase 2 was
      markedly increased. In groups 3 and 4, only very slight intestinal injury was
      observed. The tissue level of interleukin-8, tumor necrosis factor-alpha,
      malondialdehyde, prostaglandin E2, tromboxane B2, and nitric oxide were
      significantly decreased in comparison to the group 2. Meanwhile, the abundance of
      inducible nitric oxide synthase and cyclooxygenase 2 was also marked decreased in
      comparison to group 2. The current study suggests a therapeutic role of TFF3 in
      an experimental model of NEC. Our findings may open a new insight into the
      treatment of NEC in newborns.

PMID- 14599716
TI  - Expression and localization of AT1 receptors in hepatic Kupffer cells: its
      potential role in regulating a fibrogenic response.
AB  - Previous studies have showed that the renin-angiotensin system (RAS) plays an
      important role in the pathogenesis of liver cirrhosis. The localization of
      angiotensin II receptor in hepatic stellate cells opens up a new research
      direction of RAS in the regulation of liver fibrosis. However, the potential role
      of angiotensin II on Kupffer cells remains unexplored. As Kupffer cells are
      actively involved in the fibrotic process, the present study aimed, specifically,
      to demonstrate the presence of key RAS components, with particular reference to
      the AT(1) receptor, and its potential role in hepatic Kupffer cells. The
      expression of key RAS components in rat liver and isolated hepatic Kupffer cells
      was analyzed by RT-PCR. The expression and precise localization of AT(1)
      receptors in hepatic Kupffer cells were investigated by Western blot analysis and
      immunofluorescent double staining, respectively. The effect of angiotensin
      stimulated Kupffer cells on the expression of the fibrogenic factors, i.e.
      transforming growth factor-beta (TGF-beta) and fibronectin, was examined by semi
      quantitative RT-PCR. RT-PCR analysis showed that mRNA of several key RAS
      components-angiotensin II receptors, angiotensinogen, renin and angiotensin
      converting enzyme, particularly the AT(1) receptors, was expressed in the liver
      and isolated hepatic Kupffer cells. The AT(1) receptor protein was consistently
      expressed in hepatic Kupffer cells as evidenced by Western blot analysis. Double
      immunostaining confirmed that the AT(1) receptors were specifically localized to
      the Kupffer cells from the liver and isolated hepatic Kupffer cells. On the other
      hand, angiotensin II stimulated mRNA expression of TGF-beta and fibronectin,
      which could be inhibitable by saralasin and losartan, the nonselective and
      specific antagonists for AT(1) receptors, respectively. The present findings
      clearly demonstrated the expression, localization and potential role of local RAS
      components with particular emphasis on the AT(1) receptors in hepatic Kupffer
      cells. The intimate interaction of angiotensin II with its AT(1) receptor located
      in the Kupffer cells and its fibrogenic action may represent a regulatory
      mechanism in the development of liver fibrosis such as inflammation and
      cirrhosis.

PMID- 14599717
TI  - NPY, NPY receptors, and DPP IV activity are modulated by LPS, TNF-alpha and IFN
      gamma in HUVEC.
AB  - Since NPY increases endothelial cell (EC) stickiness for leukocytes, we studied
      the effects of LPS, TNF-alpha and IFN-gamma on its expression and action in
      HUVEC. Cytokines raised NPY and pro-NPY intracellular content and dipeptidyl
      peptidase IV (DPP IV) activity. Y1 and Y2 receptors were expressed in basal
      conditions, and LPS, TNF-alpha and IFN-gamma induced Y5 receptor expression with
      a concomitant extinction of Y2 receptor expression. NPY induced an intracellular
      calcium increase mainly mediated by Y2 and Y5 receptors in basal conditions.
      After stimulation with LPS, TNF-alpha and IFN-gamma, calcium increase was mainly
      caused by Y5 receptor. The modulation of the NPY system by LPS, TNF-alpha and IFN
      gamma, and the NPY-induced calcium signaling suggest a role for NPY during the
      inflammatory response.

PMID- 14599718
TI  - Comparative study of biological activity of insulins of lower vertebrates in the
      novel adenylyl cyclase test-system.
AB  - The biological activity of insulins of lower vertebrates (teleosts-Oncorhynchus
      gorbuscha, Scorpaena porcus, chondrosteans-Acipenser guldenstaedti and
      cyclostomates-Lamperta fluviatilis) was studied and compared with that of
      standard pig insulin. The determination of biological activity was made using the
      novel adenylyl cyclase (AC) test-system based on the adenylyl cyclase signaling
      mechanism (ACSM) of insulin action discovered earlier by the authors. The
      biological activity of insulins was estimated as EC(50), i.e. concentration
      leading to half-maximal activating effect of the hormone (10(-11)-10(-7) M), in
      vitro, on adenylyl cyclase in two types of the target tissues: in membrane
      fractions of the muscles of rat and mollusc Anodonta cygnea. In rat, the
      efficiency of insulins was found to decrease in the following order: pig
      insulin>scorpaena insulin>gorbuscha insulin>sturgeon insulin>lamprey insulin. In
      the mollusc, the order was different: sturgeon insulin>scorpaena insulin>pig
      insulin>gorbuscha insulin. Lamprey insulin at the same concentrations did not
      apparently reach the maximal adenylyl cyclase activating effect. The suggestion
      was made that differences in the biological activity of insulins depend on the
      hormone structure and a number of indexes characteristic of the adenylyl cyclase
      test-system in the vertebrate and invertebrate tissues. The proposed adenylyl
      cyclase test-system is highly sensitive to insulin at physiological
      concentrations, has good reproduction and is easy to apply.

PMID- 14599719
TI  - Effect of exogenous cholecystokinin on islet blood flow in anesthetized rats.
AB  - Although a number of studies have investigated the effect of cholecystokinin
      (CCK) on pancreatic blood flow and exocrine function, few have addressed the
      effect of CCK on islet blood flow. Here, we studied the effect of exogenous CCK
      on islet blood flow in anesthetized rats. Islet blood flow was measured by the
      color microsphere method. Bolus intravenous administration of CCK (10 microg/kg)
      significantly increased pancreatic and islet blood flow in control Long-Evans
      Tokushima Otsuka (LETO) rats, but not in Otsuka Long-Evans Tokushima Fatty
      (OLETF) rats lacking CCK-A receptors. Since fractional islet blood flow expressed
      as a percentage of whole pancreatic blood flow was decreased after CCK
      administration in LETO rats, the vasodilating effect of CCK appeared to be
      stronger in exocrine than endocrine tissue. Although vagotomy failed to alter the
      CCK-induced increase in pancreatic and islet blood flow, pretreatment with nitric
      oxide synthase inhibitor N(G)-monomethyl-L-arginine completely prevented the
      increase in pancreatic and islet blood flow. Our results demonstrated that
      exogenous CCK is a potent vasodilator of exocrine as well as islet vasculature
      via CCK-A receptors, and that such action is mediated by a NO-dependent mechanism
      rather than by vagal mechanisms.

PMID- 14599721
TI  - Differential effect of protein and fat on plasma ghrelin levels in man.
AB  - Ghrelin, a gastric hormone that stimulates food intake is decreased after
      ingestion of carbohydrate-rich meals. The acute effect of fat- and protein-rich
      meals on plasma ghrelin levels is still unknown. Accordingly, plasma ghrelin
      levels were determined in 10 healthy volunteers after ingestion of the three
      macronutrients and during vagal stimulation by modified sham feeding and
      following gastric distension with a highly viscous guar solution. After a solid
      carbohydrate-rich test meal ghrelin levels fell from 559+/-59.3 pg/ml to a nadir
      of 449+/-47.4 pg/ml within 60 min (p<0.05). Following an oral glucose load (75 g
      in 300 ml water), a similar decrease was observed (p<0.05). A fat-rich meal also
      decreased plasma ghrelin levels (p<0.05) leading to a nadir towards the end of
      the study period at 180 min. Protein intake, however, stimulated plasma ghrelin
      levels from 449+/-68.1 to a plateau of 520 pg/ml (p<0.05). There was no
      significant change of ghrelin levels after modified sham feeding or gastric
      distension. In conclusion, the decrease of ghrelin levels after fat ingestion
      shows a different time pattern compared to carbohydrate, while protein ingestion
      stimulated ghrelin levels. This suggests that different and as yet unknown
      mechanisms contribute to the regulation of postprandial ghrelin release in man
      depending on the ingested macronutrients. Cephalic-vagal and intragastric neural
      mechanisms most likely do not contribute to the postprandial regulation of
      ghrelin secretion.

PMID- 14599720
TI  - Fibrosis rather than blood pressure determines cardiac BNP expression in mice.
AB  - BACKGROUND: Since first reports demonstrated interactions between the natriuretic
      peptide (NPS) and renin-angiotensin system (RAS), our experiments should clarify
      whether cardiac brain natriuretic peptide (BNP) is regulated in mice genetically
      altered for components of the RAS. METHODS AND RESULTS: The study was carried out
      in hypotensive AT1- and angiotensinogen (ANG)-, and normotensive AT2-knockout
      mice, and in hypertensive animals overexpressing ANG and wildtype controls of
      each genotype. Ventricular BNP expression was analyzed by RNase-protection assay
      (RPA) (n=6). Cardiac fibrosis was visualized by Sirius red staining. While ANG
      overexpression increases cardiac BNP-mRNA expression (1035+/-210 vs. wildtype:
      405+/-95 in PSL/mm(2), P<0.01), its deficiency had no influence. Both AT1- and
      AT2-knockouts showed significantly decreased BNP-mRNA concentrations (AT1: 21+/-6
      vs. wildtype: 139+/-28 in PSL/mm(2), P<0.001; AT2: 8+/-2 vs. 19+/-3 in PSL/mm(2),
      P<0.05). These alterations correlate to reduced cardiac fibrosis in AT2-deficient
      animals, and an unchanged matrix content in ANG knockouts. CONCLUSIONS: Increased
      BNP-mRNA levels in hypertensive ANG-overexpressing mice and decreased BNP in
      hypotensive AT1-deficient animals suggest that this mRNA expression is blood
      pressure-dependent. However, the observed alterations of fibrosis and the
      unchanged BNP in hypotensive ANG knockouts and impaired BNP-mRNA expression in
      normotensive AT2-deficient mice demonstrate a direct interaction of the RAS and
      NPS that is fibrosis- rather than blood pressure-dependent.

PMID- 14599722
TI  - Anti-inflammatory effects of leptin and cholecystokinin on acetic acid-induced
      colitis in rats: role of capsaicin-sensitive vagal afferent fibers.
AB  - Leptin and cholecystokinin (CCK) have a synergistic interaction in the
      suppression of food intake, and afford similar gastroprotective activity. The
      present study was designed to investigate the putative protective effects of CCK
      and leptin on acute colonic inflammation. Leptin or CCK-8s was injected to rats
      intraperitoneally immediately before and 6 h after the induction of colitis with
      acetic acid. CCK-A receptor antagonist (L-364,718) or CCK-B receptor antagonist
      (L-365,260) was injected intraperitoneally 15 min before leptin or CCK
      treatments. In a group of rats, vagal afferent fibers were denervated by topical
      application of capsaicin on the cervical vagi. Rats were decapitated at 24 h, and
      the distal 8 cm of the colon were removed for macroscopic scoring, determination
      of tissue wet weight index (WWI), histologic assessment and tissue
      myeloperoxidase (MPO) activity. All inflammation parameters were increased by
      acetic acid-induced colitis compared to control group. Leptin or CCK-8s treatment
      reduced these parameters in a similar manner, while co-administration of leptin
      and CCK was found to be more effective in reducing the macroscopic score and WWI.
      CCK-8s-induced reduction in the score and WWI was prevented by CCK-A, but not by
      CCK-B receptor antagonist, whereas neither antagonist altered the inhibitory
      effect of leptin on colitis-induced injury. On the other hand, perivagal
      capsaicin prevented the protective effects of both CCK-8s and leptin on colitis.
      Our results indicate that leptin and CCK have anti-inflammatory effects on acetic
      acid-induced colitis in rats, which appear to be mediated by capsaicin-sensitive
      vagal afferent fibers involving the reduction in colonic neutrophil infiltration.

PMID- 14599723
TI  - Natural killer cell functions mediated by the neuropeptide substance P.
AB  - The neuropeptide substance P (SP) can modulate a number of immunological
      functions in vitro and in vivo. Here, we investigated if SP boosts migration and
      cytotoxicity of natural killer cells, thus providing a further link between
      "innate immunity" and neurogenic inflammatory processes like asthma bronchiale.
      We demonstrate a dose-dependent effect of SP on natural killer cell migration
      with a maximal response at 10(-8) M SP. SP was shown to stimulate unstimulated as
      well as interleukin-2 (IL-2)-activated natural killer cells. Stimulation of
      natural killer cell migration was neurokinin-1 receptor dependent. Furthermore,
      mRNA encoding the neurokinin-1 receptor was demonstrated as being present in
      natural killer cells using RT-PCR while mRNA of the neurokinin-2 receptor was not
      detectable. Additionally, SP seems to influence specific cytotoxicity against
      Raji and K567 effector cells by a receptor-independent mechanism. In conclusion,
      our data indicate that functionally active neurokinin-1 receptors can be
      expressed by human natural killer cells. Substance P might therefore be a novel
      link between neural structures and innate immunity.

PMID- 14599724
TI  - A comparison of the neuropeptides from the retrocerebral complex of adult male
      and female Manduca sexta using MALDI-TOF mass spectrometry.
AB  - The occurrence of neuropeptides in the retrocerebral complexes of adult male and
      females of the tobacco hawkmoth, Manduca sexta, was investigated using matrix
      assisted laser desorption time of flight (MALDI-TOF) mass spectrometry (MS), post
      source decay (PSD) and collision-induced dissociation (CID) MS/MS. From fractions
      of methanol extracts of corpora cardiaca (CC)/corpora allata (CA), separated by
      reversed-phase high performance liquid chromatography (RP-HPLC), a total of 11
      mass ions were assigned to known peptides from M. sexta. These peptides were
      adipokinetic hormone (AKH), FLRFamides I, II and III, crustacean cardioactive
      peptide (CCAP), cardioactive peptide 2b (CAP(2b)), three myoinhibitory peptides,
      corazonin, and M. sexta allatostatin (Manse-AS). A further six masses were in
      agreement with Y/FXFGLamide allatostatins identified from other Lepidoptera. The
      sequence identities of FLRFamide I and AKH were confirmed using post source decay
      analysis. Fragmentation by collision-induced dissociation MS/MS identified an
      extended AKH peptide. The apparent differences in the peptides present in male
      and female retrocerebral complexes are most likely quantitative rather than sex
      specific.

PMID- 14599725
TI  - Identification of three novel Phyllomedusa sauvagei dermaseptins (sVI-sVIII) by
      cloning from a skin secretion-derived cDNA library.
AB  - The defensive skin secretions of many amphibians contain a wide spectrum of
      biologically active compounds, particularly antimicrobial peptides that act as a
      first line of defence against bacterial infection. Here we describe for the first
      time the identification of three novel dermaseptin-related peptides (dermaseptins
      sVI-sVIII) whose primary structures were deduced from cDNAs cloned from a library
      constructed from lyophilised skin secretion of the South American hylid frog,
      Phyllomedusa sauvagei. The molecular masses of each were subsequently confirmed
      by interrogation of archived LC/MS files of fractionated skin secretion followed
      by automated Edman degradation sequencing. The heterogeneity of primary
      structures encountered in amphibian skin antimicrobial peptides may in part be
      explained by individual variation-a factor essential for selective functional
      molecular evolution and perhaps, ultimately in speciation.

PMID- 14599726
TI  - Kinestatin: a novel bradykinin B2 receptor antagonist peptide from the skin
      secretion of the Chinese toad, Bombina maxima.
AB  - We have isolated a novel bradykinin B(2)-receptor antagonist peptide, kinestatin,
      from toad (Bombina maxima) defensive skin secretion. Mass spectroscopy
      established a molecular mass of 931.56 Da and a provisional structure: pGlu
      Leu/Ile-Pro-Gly-Leu/Ile-Gly-Pro-Leu/Ile-Arg.amide. The unmodified sequence, 
      QIPGLGPLRG-, was located at the C-terminus of a 116-amino-acid residue open
      reading frame following interrogation of a sequenced B. maxima skin cDNA library
      database. This confirmed the presence of appropriate primary structural
      attributes for the observed post-translational modifications present on the
      mature peptide and established residue 2 as Ile and residues 5/8 as Leu.
      Kinestatin represents a prototype novel peptide from amphibian skin.

PMID- 14599728
TI  - Effect of the brain and suboesophageal ganglion on pupal development in
      Helicoverpa armigera through regulation of FXPRLamide neuropeptides.
AB  - Recent studies in Helicoverpa armigera report a novel role for diapause hormone
      (DH), pheromone biosynthesis activating neuropeptide (PBAN) and three other
      FXPRLamide neuropeptides secreted from suboesophageal ganglion (SG) in
      terminating pupal diapause. In the present paper, we investigated the role of
      these five FXPRLamide family neuropeptides on pupal development. Although removal
      of SG could not make nondiapause-destined pupae enter diapause-like status, it
      did make them eclose approximately 0.6-1.2 days later when compared with the
      controls. The results of competitive ELISAs showed a high level of FXPRLamide
      titer in the hemolymph of the SG-removed pupae and this may be due to the
      expression of the DH-PBAN gene in tissues other than SG. DH-PBAN mRNA and
      peptides were also detected in the thoracic ganglia (TGs) by RT-PCR and
      immunocytochemistry. The expression of DH-PBAN gene in the TGs of the SG-removed
      pupae is significantly higher than that in normal pupae by quantitative PCR and
      immunocytochemistry. Decerebration experiments proved that the decerebrated pupae
      could enter diapause-like status through down-regulation of FXPRLamide titer in
      hemolymph. Our studies confirm that the brain plays an important role in the
      determination of pupal development by regulating the synthesis and release of
      FXPRLamide neuropeptides in H. armigera. Thus, the function of FXPRLamide
      peptides in H. armigera is closely correlated with pupal development.

PMID- 14599727
TI  - Long-term estradiol treatment improves VIP-mediated vasodilation in
      atherosclerotic proximal coronary arteries.
AB  - The aim of the present study was to evaluate the impact of long-term estrogen
      replacement therapy (ERT) on the vasodilatory effect of the two peptides
      vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase
      activating polypeptide (PACAP) in atherosclerotic coronary and cerebral arteries.
      Female ovariectomized homozygous Watanabe heritable hyperlipidemic rabbits were
      randomized to 16 weeks treatment with 17beta-estradiol or placebo. The diet was
      semisynthetic, thereby avoiding the influence of phytoestrogens. Artery ring
      segments were mounted for isometric tension recordings in myographs. Following
      precontraction, the dose-response relationships for VIP and PACAP were
      evaluated.Treatment with 17beta-estradiol significantly improved the maximum VIP
      mediated vasodilation (E(max), percentage of precontraction) in proximal coronary
      arteries (45.8+/-9.6% vs. 24.1+/-3.7%, p<0.05). In the same artery segment,
      17beta-estradiol induced a significant decrease in the relative ratio between the
      repeated contractile response to potassium 30 and 120 mM (100+/-7% vs. 132+/-11%,
      p<0.05). For distal coronary arteries, there was a tendency to similar changes,
      but no statistical differences for the potassium or VIP responses in cerebral or
      distal coronary arteries were found between the two groups. 17beta-estradiol
      induced no changes in the PACAP-mediated vasodilation. These results suggest that
      long-term treatment with 17beta-estradiol improves the VIP-mediated but not the
      PACAP-mediated vasodilation in atherosclerotic proximal coronary arteries.

PMID- 14599729
TI  - Intimate partner violence and depression among Whites, Blacks, and Hispanics.
AB  - PURPOSE: To examine the relationship between intimate partner violence and
      depression. METHODS: A household probability sample of Whites (n=616), Blacks
      (n=377), and Hispanics (n=592) age 18 or older was interviewed in 1995. The
      response rate was 85%. Logistic analysis is used to identify predictors of
      depression. RESULTS: Among men, Black (OR=.29; 95% CI, 0.13-.65) and Hispanic
      (OR=0.4; 95% CI, 0.2-0.8) ethnicity were protective against depression. Factors
      of risk for men included victimization by female to male partner violence
      (OR=4.04; 95% CI, 1.15-14.11), unemployment (OR=7.65; 95% CI, 1.59-16.39), and
      living in a high-unemployment neighborhood (OR=4.6; 95% CI, 1.86-11.37). Among
      women, the predictors are perpetration of moderate (OR=4.08; 95% CI, 1.33-12.47)
      or severe (OR=6.57; 95% CI, 1.76-24.52) female to male partner violence, and
      impulsivity (OR=1.82; 95% CI, 3.87-20.71). CONCLUSIONS: Knowledge from surveys
      using general population samples is important for developing prevention
      interventions in the community. Because predictors of depression in these samples
      are both individual and contextual at neighborhood level, prevention
      interventions to be effective must address not only individual factors of risk
      but also structural conditions in the environment where individuals live.

PMID- 14599730
TI  - Sex-race differences in the relationship between obesity and asthma: the
      behavioral risk factor surveillance system, 2000.
AB  - PURPOSE: Although prospective data are limited, recent cross-sectional studies
      support obesity as a cause of asthma. They also suggest that the association is
      present only among women. Our analysis examines possible sex-race differences in
      the relationship between obesity and asthma. METHODS: We examined data from the
      2000 Behavioral Risk Factor Surveillance System. To minimize diagnostic bias, the
      sample was limited to adults aged 18 to 34 years. All cases had doctor-diagnosis
      of asthma and ongoing symptoms. Multiple logistic regression was used to examine
      risk factors for current asthma vs. never having asthma. RESULTS: Obesity and
      asthma were more strongly related among women than men (test for interaction,
      p<0.01). Across increasing categories of body mass index (BMI), we observed a
      dose-response relationship among women (odds ratios: 0.9, 1.0 [reference], 1.0,
      1.3, 1.5, 1.8, and 3.2) but only a non-significant increased risk in severely
      obese men (odd ratio: 2.0). In subgroup analyses, however, the obesity-asthma
      association was present in four of six sex-race/ethnicity subgroups, including
      black and Hispanic men. CONCLUSIONS: Although the obesity-asthma association is
      stronger among women than men, our analysis demonstrates a strong positive
      association among men from minority groups. These race-specific results may help
      explain some of the "inconsistencies" in prior studies.

PMID- 14599731
TI  - Relationship of total and abdominal adiposity with CRP and IL-6 in women.
AB  - PURPOSE: To examine the relationship between different measures of adiposity as
      predictors of C-reactive protein (CRP) and interleukin-6 (IL-6) levels. METHODS:
      A cross-sectional study of 733 women free from preexisting cardiovascular disease
      or cancer at baseline. MEASUREMENTS: Total adiposity, as measured by body mass
      index (BMI). Abdominal adiposity, as measured by waist circumference (WC) and
      waist/hip ratio (WHR). High sensitivity CRP levels and IL-6 levels. RESULTS: BMI,
      WHR, and WC were all significantly correlated with CRP and IL-6, throughout the
      anthropometric spectrum. After adjustment for risk factors, the odds ratios (ORs)
      were 12.2 (95% CI, 6.44-23.0) for elevated CRP (>/=75th percentile) and 4.13 (95%
      CI, 2.37-7.18) for elevated IL-6 (>/=75th percentile) in comparisons of extreme
      BMI quartiles. Among women in the highest WC quartile, the OR for elevated CRP
      and IL-6 were 8.57 (95% CI, 4.59-16.0) and 4.40 (95%CI, 2.46-7.89), while ORs for
      the highest WHR quartile were 2.88 (95% CI, 1.60-5.19) and 1.76 (95% CI, 1.03
      3.01), respectively. Compared with lean nonusers, women in the highest BMI
      quartile who did not use hormone therapy (HT) had an OR for elevated CRP of 7.79
      (95% CI, 2.08-29.2) vs. 31.6 (95% CI, 7.97-125.6) for current hormone users.
      CONCLUSIONS: Indices of both total and abdominal adiposity were strongly
      associated with significant increased levels of CRP and IL-6. This association
      was evident across the entire spectrum of BMI.

PMID- 14599732
TI  - Waist to stature ratio is more strongly associated with cardiovascular risk
      factors than other simple anthropometric indices.
AB  - PURPOSE: To determine which is the best anthropometric index among body mass
      index (BMI), waist circumference (WC), waist to hip ratio (WHR) and waist to
      stature ratio (WSR) in relation to cardiovascular risk factors. METHODS: A
      representative sample of 2895 Hong Kong Chinese aged 25 to 74 years received
      medical examinations in 1995 and 1996. Anthropometric indices and cardiovascular
      risk factors in blood were measured, and partial correlation and Receiver
      Operator Characteristic (ROC) curves were used in analysis. RESULTS: Among 11
      cardiovascular risk factors in partial correlation analysis, including ties WSR
      had the highest r in 6 in men, and 5 in women; followed by WC with 4 in men and 6
      in women. In ROC analyses of 21 risk factors and health conditions, the area
      under curve (AUC) of WSR was the largest for most (13 of 21) factors in men and
      10 in women; followed by WHR with 14 in women but only 5 in men. The optimal WSR
      cutoff value was 0.48 for both men and women. CONCLUSIONS: WSR is the best simple
      anthropometric index in predicting a wide range of cardiovascular risk factors
      and related health conditions. A simple message that one's waist circumference
      should not exceed half the stature is recommended for the public.

PMID- 14599733
TI  - Bone mineral density and mortality in women and men: the NHANES I epidemiologic
      follow-up study.
AB  - PURPOSE: We sought to assess the long-term association of bone mineral density
      with total, cardiovascular, and non-cardiovascular mortality. METHODS: The First
      National Health and Nutrition Examination Survey data were obtained from a
      nationally representative sample of non-institutionalized civilians. A cohort
      aged 45 through 74 years at baseline (1971-1975) was observed through 1992.
      Subjects were followed for a maximum of 22 years. Included in the analyses were
      3501 white and black subjects. Death certificates were used to identify a total
      of 1530 deaths. RESULTS: Results were evaluated to determine the relative risk
      for death per 1 SD lower bone mineral density, after controlling for age at
      baseline, smoking status, alcohol consumption, history of diabetes, history of
      heart disease, education, body mass index, recreational physical activity, and
      blood pressure medication. Bone mineral density showed a significant inverse
      relationship to mortality in white men and blacks, but did not reach significance
      in white women. Based on 1 SD lower bone mineral density, the relative risk for
      white men was 1.16 (95% confidence interval (CI), 1.07-1.26, p<.01), while for
      white women the relative risk was 1.10 (95% CI, 0.99-1.23, p=.07), and in blacks
      the relative risk was 1.22 (95% CI, 1.05-1.42, p<.01). Bone mineral density was
      also associated with non-cardiovascular mortality in all three race-gender
      groups. An association between bone mineral density and cardiovascular mortality
      was found only in white men. CONCLUSIONS: Bone mineral density is a significant
      predictor of death from all causes (white men, blacks), cardiovascular (white men
      only) and other causes combined, in whites and blacks.

PMID- 14599734
TI  - Low risk of hip fracture among elderly breast cancer survivors.
AB  - PURPOSE: Prior research has shown that women with either osteoporotic fracture or
      low bone density are at a decreased risk of breast cancer. Little prior work has
      evaluated whether women with breast cancer are at a decreased risk of
      osteoporotic fracture. METHODS: We used data from the National Cancer Institute's
      Surveillance Epidemiology and End Results (SEER)-Medicare program to study the
      risk of hip fracture among elderly female Medicare beneficiaries with and without
      histories of breast cancer. Using the SEER file, we identified elderly women
      survivors of stage 0, I, or II breast cancer (N=5980) diagnosed between the ages
      of 55 and 64 years; using the Medicare 5% file, we identified elderly women
      without histories of cancer (N=23,165) from SEER regions. Using Medicare claims
      from 1993 through 1998, we followed women for hospitalization for hip fracture or
      death until December 31, 1998. RESULTS: We found the rate ratio of
      hospitalization for hip fracture for breast cancer survivors relative to
      comparison patients was 0.63 (95% CI: 0.43-0.94) after adjusting for age, race,
      socioeconomic status, geographic location, cohort entry year, and medical
      comorbidity. CONCLUSIONS: We conclude that survivors of early stage post
      menopausal breast cancer are at significantly lower risk of hip fracture than
      women who do not have histories of breast cancer.

PMID- 14599735
TI  - Impact of the LDS church's health doctrine on deaths from diseases and conditions
      associated with cigarette smoking.
AB  - PURPOSE: This study provides a quantitative assessment of the impact the LDS
      Church's health doctrine has on deaths and years of potential life lost (YPLL)
      from diseases and conditions associated with cigarette smoking in Utah. METHODS:
      Pooled estimates of relative risk from review articles and meta-analyses in
      combination with 1996 Utah smoking prevalence data were used to calculate smoking
      attributed etiologic fractions, deaths, and YPLL. RESULTS: Numbers of deaths
      attributed to smoking between 1994 and 1998 in Utah are 1730 for LDS men, 721 for
      LDS women, 1739 for non-LDS men, and 1138 for non-LDS women. Corresponding annual
      crude death rates attributed to smoking (per 100,000) are 46.5, 18.9, 133.9, and
      90.1. YPLL due to smoking for the study period are 22,338 for LDS men, 9205 for
      LDS women, 21,771 for non-LDS men, and 13,168 for non-LDS women. Corresponding
      YPLL crude rates are 600.6, 241.2, 1676.7, and 1043.3. If smoking-attributed
      death and YPLL rates for non-LDS matched LDS, there would be 1135 fewer deaths
      for men and 899 fewer deaths for women, and 13,973 fewer years of life lost for
      men and 10,124 fewer YPLL for women between 1994 and 1998 in Utah. CONCLUSIONS:
      The LDS Church's health doctrine concerning tobacco goes beyond health risk
      information and social and financial considerations to include a religious
      dimension. Consequently, LDS experience a comparatively low burden of death and
      YPLL attributed to smoking.

PMID- 14599736
TI  - Lifestyle risk factors and chronic kidney disease.
AB  - PURPOSE: To examine the effects of lifestyle risk factors such as alcohol
      consumption, cigarette smoking and body mass index (BMI) on the development of
      chronic kidney disease. METHODS: We used a case-control study of 554 hospital
      cases and 516 age, race, and gender-matched community controls. The main outcome
      measure was newly-diagnosed chronic kidney disease, assessed by chart review.
      Self-reported history of alcohol consumption, smoking, and BMI as well as other
      co-variables were obtained during telephone interviews. Logistic regression
      models assessed the association between lifestyle risk factors and chronic kidney
      disease and were adjusted for important co-variables. RESULTS: We found no
      significant associations between alcohol consumption and chronic kidney disease,
      with the exception of moonshine, which resulted in an increased risk of chronic
      kidney disease (including all subtypes). The effects of smoking on chronic kidney
      disease were inconsistent, but pointed to no appreciable excess risk among
      smokers. Increasing quartiles of BMI were positively and significantly associated
      with nephrosclerosis (ORs [95% CI]: 2.5 [1.0-6.0], 2.8 [1.2-6.8] and 4.6 [1.8
      11.6], for the second, third, and fourth quartiles of BMI, respectively).
      CONCLUSIONS: Our study revealed a significant positive association between BMI
      and nephrosclerosis. We did not find an increased risk of chronic kidney disease
      associated with alcohol or cigarette smoking.

PMID- 14599738
TI  - Financial conflicts of interest in the scientific publication world--and other
      good news.

PMID- 14599737
TI  - Assessment of a national health interview survey-based method of measuring
      community socioeconomic status.
AB  - PURPOSE: Increasingly researchers are interested in assessing the role of
      community socioeconomic status (SES) in poor health outcomes, above and beyond
      the influence of low individual SES. However, the feasibility of conducting these
      multi-level studies is often limited by restrictions on release of confidential
      identifiers for linkage to census data, resources for the linkage, and the
      availability of data sources with individual SES measures. This study assessed a
      new method of measuring community socioeconomic status (SES) that can be used
      with the publicly available National Health Interview Survey (NHIS) and preserves
      confidentiality and can be used with individual SES measures from the NHIS.
      METHODS: The associations between community SES and mortality from all causes and
      breast cancer in women were assessed in two samples: 1) deaths in 1987-1993 NHIS
      respondents linked to community SES measures developed with the new method; and
      2) deaths in 1991 from the National Multiple Cause of Death Files linked to 1990
      county-level census SES measures. The magnitude of crude mortality rates,
      direction of trend, and age-adjusted relative risk of mortality for low vs. high
      SES were compared in the two samples. RESULTS: Crude all-cause mortality and
      breast cancer mortality rates were similar in both samples in terms of magnitude
      and direction of trend. In both samples, as SES decreased, rates of all-cause
      mortality increased, whereas breast cancer mortality rates tended to decrease.
      Age-adjusted relative risks of mortality from all causes and breast cancer for
      low vs. high SES were similar in the two samples. CONCLUSIONS: Similarity of
      associations between community SES and mortality from all causes and breast
      cancer in the two samples provides support for the validity of a new NHIS-based
      method of measuring community SES. Since the NHIS is a large, nationally
      representative survey with high response rates and low loss to mortality follow
      up, this method represents an important resource for multi-level studies.

PMID- 14599739
TI  - Nucleic acid structures and enzymes in the immunoglobulin class switch
      recombination mechanism.
AB  - Class switch recombination is the gene rearrangement process by which our B
      lymphocytes change from IgM production to IgG, IgA, or IgE. Unlike the well
      characterized V(D)J recombination, the mechanism of class switch recombination
      has been largely enigmatic until very recent progress has begun to shed light on
      this gene rearrangement process. Progress has been made on the enzymes involved
      in leading to the DNA cleavage events and on identifying the unusual DNA
      structures that those enzymes recognize.

PMID- 14599740
TI  - xni-deficient Escherichia coli are proficient for recombination and multiple
      pathways of repair.
AB  - Single-strand-dependent DNA exonucleases play important roles in DNA repair and
      recombination in all organisms. In Escherichia coli the redundant functions
      provided by the RecJ, ExoI, ExoVII and ExoX exonucleases are required for
      mismatch repair, UV resistance and homologous recombination. We have examined
      whether the xni gene product, the single-strand exonuclease ExoIX, is also a
      member of this group. We find that deletion of xni has no effect on the above
      processes, or on resistance to oxidative damage, even in combination with other
      exonuclease mutations. We conclude that the xni gene product does not belong to
      this group of nucleases that play redundant roles in DNA recombination and
      repair.

PMID- 14599741
TI  - UV-induced de novo protein synthesis enhances nucleotide excision repair
      efficiency in a transcription-dependent manner in S. cerevisiae.
AB  - DNA damage results in the up-regulation of several genes involved in different
      cellular physiological processes, such as the nucleotide excision repair (NER)
      mechanism that copes with a broad range of DNA alterations, including the
      carcinogenic ultraviolet (UV) light-induced pyrimidine dimers (PDs). There are
      two NER sub-pathways: transcription coupled repair (TCR) that is specific for the
      transcribed strands (TS) of active genes and global genomic repair (GGR) that
      repairs non-transcribed DNA sequences (NTD) and the non-transcribed strands (NTS)
      of expressed genes. To elucidate the role of UV-dependent de novo protein
      synthesis in nucleotide excision repair in the budding yeast, we investigated the
      effect of the protein synthesis inhibitor, cycloheximide, on the removal of PDs.
      Log phase as well as G(1)-synchronized cells were treated with the drug shortly
      before UV irradiation and immediately thereafter, and the repair of damaged DNA
      was assessed with the high resolution primer extension technique. The results
      show that in both cellular conditions, the inhibition of UV-dependent de novo
      protein synthesis by cycloheximide impairs the excision repair of the
      transcriptionally active GAL10 and URA3 genes, with a greater effect on the non
      transcribed strands. This indicates that UV-mediated de novo protein synthesis is
      required for efficient nucleotide excision repair, but not for the preferential
      repair of the TSs. On the other hand, cycloheximide did not affect the repair of
      either strand of the repressed GAL10 gene or the non-transcribed promoter region
      of the URA3 gene, showing that UV-induced de novo protein synthesis is not
      required for PD removal from transcriptionally inactive DNA sequences. Together,
      these data show that despite the fact that NTD and NTSs are normally repaired by
      the GGR sub-pathway, their requirement for UV-dependent de novo protein synthesis
      is different, which may suggest a difference in the processing of UV lesions in
      these non-transcribed sequences of the genome.

PMID- 14599742
TI  - Strand-specific processing of 8-oxoguanine by the human mismatch repair pathway:
      inefficient removal of 8-oxoguanine paired with adenine or cytosine.
AB  - Genomic DNA and its precursors are susceptible to oxidation during aerobic
      cellular metabolism, and at least five distinct repair activities target a single
      common lesion, 7,8-dihydro-8-oxoguanine (8-oxoG). The human mismatch repair (MMR)
      pathway, which has been implicated in an apoptotic response to covalent DNA
      damage, is likely to encounter 8-oxoG in both the parental and daughter strand
      during replication. Here, we show that lesions containing 8-oxoG paired with
      adenine or cytosine, which are most likely to arise during replication, are not
      efficiently processed by the mismatch repair system. Lesions containing 8-oxoG
      paired with thymine or guanine, which are unlikely to arise, are excised in an
      MSH2/MSH6-dependent manner as effectively as the corresponding mismatches when
      placed in a context that reflects the daughter strand during replication. Using a
      newly developed assay based on methylation sensitivity, we characterized strand
      excision events opposite 8-oxoG situated to reflect placement in the parental
      strand. Lesions that efficiently trigger strand excision and resynthesis (8-oxoG
      paired with thymine or guanine) result in adenine or cytosine insertion opposite
      8-oxoG. These latter pairings are poor substrates for further action by mismatch
      repair, but precursors for alternative pathways with non-mutagenic outcomes. We
      suggest that the lesions most likely to be encountered by the human mismatch
      repair pathway during replication, 8-oxoG.A or 8-oxoG.C, are likely to escape
      processing in either strand by this system. Taken together, these data suggest
      that the human mismatch repair pathway is not a major contributor to removal of
      misincorporated 8-oxoG, nor is it likely to trigger repeated attempts at lesion
      processing.

PMID- 14599743
TI  - Abnormal kinetics of induction of UV-stimulated recombination in human DNA repair
      disorders.
AB  - Recombination can result in genetic instability, and thus constitutes an
      important factor in the carcinogenic conversion of mammalian cells. Here we
      describe the occurrence of UV-stimulated recombination called enhanced
      recombination (EREC), measured with the use of Herpes Simplex Viruses type 1
      mutants. In normal diploid human cells, EREC is induced by UV-C, mitomycin C and
      ENU, but not by X-ray or MMS. The kinetics of induction of EREC is similar to
      that of other SOS-like responses such as enhanced reactivation (ER) and enhanced
      mutagenesis (EM). In contrast to the latter responses, EREC is induced to higher
      levels and persists for longer periods in DNA repair deficient fibroblasts
      derived from xeroderma pigmentosum (XP), Cockayne syndrome (CS) and
      Trichothiodystrophy (TTD) patients. This observation indicates that EREC is a
      distinct SOS-like response. Apparently, the presence of unrepaired DNA lesions in
      the host genome is a strongly inducing signal for EREC. On the other hand, in
      cells derived from patients suffering from Bloom, Werner or Rothmund-Thomson
      syndrome (RTS) the EREC response is absent. These data indicate that determining
      EREC is a useful assay to investigate diploid human fibroblasts for abnormalities
      in UV-stimulated recombination.

PMID- 14599744
TI  - Analysis of translesion replication across an abasic site by DNA polymerase IV of
      Escherichia coli.
AB  - Unrepaired replication-blocking DNA lesions are bypassed by specialized DNA
      polymerases, members of the Y super-family. In Escherichia coli the major lesion
      bypass DNA polymerase is pol V, whereas the function of its homologue, pol IV, is
      not fully understood. In vivo analysis showed that pol V has a major role in
      bypass across an abasic site analog, with little or no involvement of pol IV.
      This can result from the inability of pol IV to bypass the abasic site, or from
      in vivo regulation of its activity. In vitro analysis revealed that purified pol
      IV, in the presence of the beta subunit DNA sliding clamp, and the gamma complex
      clamp loader, bypassed a synthetic abasic site with very high efficiency,
      reaching 73% in 2 min. Bypass was observed also in the absence of the
      processivity proteins, albeit at a 10- to 20-fold lower rate. DNA sequence
      analysis revealed that pol IV skips over the abasic site, producing primarily
      small deletions. The RecA protein inhibited bypass by pol IV, but this inhibition
      was alleviated by single-strand binding protein (SSB). The fact that the in vitro
      bypass ability of pol IV is not manifested under in vivo conditions suggests the
      presence of a regulatory factor, which might be involved in controlling the
      access of the bypass polymerases to the damaged site in DNA.

PMID- 14599746
TI  - Fission yeast Uve1 and Apn2 function in distinct oxidative damage repair pathways
      in vivo.
AB  - In Schizosaccharomyces pombe, the endonuclease Uve1 functions as the first step
      in an alternate UV photo-product repair pathway that is distinct from nucleotide
      excision repair (NER). Based upon the broad substrate specificity of Uve1 in
      vitro, and the observation that Uve1 mutants accumulate spontaneous mutations at
      an elevated rate in vivo, we and others have hypothesized that this protein might
      have a function in a mutation avoidance pathway other than UV photo-product
      repair. We show here that fission yeast Uve1 also functions in oxidative damage
      repair in vivo. We have determined the spectrum of spontaneous mutations that
      arise in uve1 null (uve1 degrees ) cells and have observed that both G-->T(C-->A)
      and T-->G(A-->C) transversions occur at an increased rate relative to wildtype
      cells. These mutations are indicative of unrepaired oxidative DNA damage and are
      very similar to the mutation spectrum observed in 8-oxoguanine glycosylase (OGG1)
      mutants in Saccharomyces cerevisiae. We have generated an apn2 null (apn2 degrees
      ) strain and shown that it is mildly sensitive to H(2)O(2). Furthermore we have
      also shown that apn2 degrees cells have an elevated rate of spontaneous mutation
      that is similar to uve1 degrees. The phenotype of apn2 degrees uve1 degrees
      double mutants indicates that these genes define distinct spontaneous mutation
      avoidance pathways. While uve1 degrees cells show only a modest sensitivity to
      the oxidizing agent hydrogen peroxide (H(2)O(2)), both uve1 degrees and apn2
      degrees cells also display a marked increased in mutation rate following exposure
      to H(2)O(2) doses. Collectively these data demonstrate that Uve1 is a component
      of multiple alternate repair pathways in fission yeast and suggest a possible
      role for Uve1 in a general alternate incision repair pathway in eukaryotes.

PMID- 14599745
TI  - DNA-PK phosphorylation sites in XRCC4 are not required for survival after
      radiation or for V(D)J recombination.
AB  - Nonhomologous end joining (NHEJ) is a major pathway for the repair of DNA double
      strand breaks (DSBs) in higher eukaryotes. Several proteins, including the DNA
      dependent protein kinase (DNA-PK), XRCC4 and DNA ligase IV, are required for
      nonhomologous end joining both in vitro and in vivo. Since XRCC4 is recruited to
      the DNA double-strand break with DNA-PK, and because the protein kinase activity
      of DNA-PK is required for its in vivo function, we reasoned that XRCC4 could be a
      potential physiological substrate of DNA-PK. Here, we have used mass spectrometry
      to map the DNA-PK phosphorylation sites in XRCC4. Two major phosphorylation sites
      (serines 260 and 318), as well as several minor sites were identified. All of the
      identified sites lie within the carboxy-terminal 100 amino acids of XRCC4.
      Substitution of each of these sites to alanine (in combination) reduced the
      ability of DNA-PK to phosphorylate XRCC4 in vitro by at least two orders of
      magnitude. However, XRCC4-deficient cells that were complemented with XRCC4
      lacking DNA-PK phosphorylation sites were analogous to wild type XRCC4 with
      respect to survival after ionizing radiation and ability to repair DSBs
      introduced during V(D)J recombination.

PMID- 14599747
TI  - Strange goings-on in the mouse germ line.
AB  - It is a conventional paradigm that mutagens lead to changes in nucleotide
      sequence when the cell attempts to repair or replicate lesions in DNA (such as
      adducts or strand breaks) that have been produced by the mutagens or their
      metabolites. The resulting changes are located at (or very near) the sites of the
      initial damage. This is the underlying theory behind mutational spectra work, but
      how general is it in vivo? Work with ionising radiation has shown that there are
      interesting things going on in the mouse germ line that do not fall within the
      conventional paradigm. Mutations occur at certain sites remote from initial DNA
      damage and in greater than expected number. Bryn Bridges discusses some recent
      papers on mutational changes in the germ line of mice following exposure to
      chemical mutagens that suggest that such phenomena may not be confined to
      radiation.

PMID- 14599748
TI  - Excision repair--its bacterial beginnings.
AB  - Nucleotide excision repair was first reported in 1964 by Setlow and Carrier and
      by Boyce and Howard-Flanders. These two reports clearly defined the existence in
      bacteria of a repair process that physically removed damaged sites, pyrimidine
      dimers, from the DNA in the form of acid-soluble fragments. These reports were
      the starting point for subsequent development of the whole field of DNA excision
      point.

PMID- 14599751
TI  - Rules vs. analogy in English past tenses: a computational/experimental study.
AB  - Are morphological patterns learned in the form of rules? Some models deny this,
      attributing all morphology to analogical mechanisms. The dual mechanism model
      (Pinker, S., & Prince, A. (1998). On language and connectionism: analysis of a
      parallel distributed processing model of language acquisition. Cognition, 28, 73
      193) posits that speakers do internalize rules, but that these rules are few and
      cover only regular processes; the remaining patterns are attributed to analogy.
      This article advocates a third approach, which uses multiple stochastic rules and
      no analogy. We propose a model that employs inductive learning to discover
      multiple rules, and assigns them confidence scores based on their performance in
      the lexicon. Our model is supported over the two alternatives by new "wug test"
      data on English past tenses, which show that participant ratings of novel pasts
      depend on the phonological shape of the stem, both for irregulars and,
      surprisingly, also for regulars. The latter observation cannot be explained under
      the dual mechanism approach, which derives all regulars with a single rule. To
      evaluate the alternative hypothesis that all morphology is analogical, we
      implemented a purely analogical model, which evaluates novel pasts based solely
      on their similarity to existing verbs. Tested against experimental data, this
      analogical model also failed in key respects: it could not locate patterns that
      require abstract structural characterizations, and it favored implausible
      responses based on single, highly similar exemplars. We conclude that speakers
      extend morphological patterns based on abstract structural properties, of a kind
      appropriately described with rules.

PMID- 14599752
TI  - Individuation of objects and events: a developmental study.
AB  - This study investigates children's ability to use language to guide their choice
      of individuation criterion in the domains of objects and events. Previous work
      (Shipley, E. F., & Shepperson, B. (1990). Countable entities: developmental
      changes. Cognition, 34, 109-136.) has shown that children have a strong bias to
      use a spatio-temporal individuation strategy when counting objects and that
      children will ignore a conflicting linguistic description in favor of this spatio
      temporal bias. Experiment 1 asked children (3-, 4-, and 5-year-olds) and adults
      to count objects and events under different linguistic descriptions. In the
      object task, subjects counted pictures of familiar objects split into multiple
      pieces (as in Shipley, E. F., & Shepperson, B. (1990). Countable entities:
      developmental changes. Cognition, 34, 109-136.) and described either using an
      appropriate kind label (e.g. "car") or the general term "thing". In the event
      task, subjects watched short animated movies consisting of a goal-oriented event
      achieved via multiple, temporally separated steps. The events were described
      either with an appropriate telic predicate targeting the goal (e.g. "paint a
      flower") or with an atelic predicate targeting the steps in the process (e.g.
      "paint") and the subjects' task was to count the events. Relative to adults,
      children preferred a spatio-temporal counting strategy in both tasks; there was
      no difference among the three groups of children. However, children were able to
      significantly change their counting strategy to follow the linguistic description
      in the event but not the object task. Experiment 2 extended the object task to
      include counting of other types of non-spatio-temporal units such as sub-parts of
      objects and collections. Results showed that children could use the linguistic
      descriptions to guide their counting strategy for these new items, though they
      continued to show a bias for a spatio-temporal individuation strategy with the
      collections. We suggest potential cognitive origins for the spatio-temporal
      individuation bias and how it interacts with children's developing linguistic
      knowledge.

PMID- 14599753
TI  - Can natural language semantics explain syllogistic reasoning?

PMID- 14599755
TI  - An artificial opposition between grammaticality and frequency: comment on
      Bornkessel, Schlesewsky, and Friederici (2002).
AB  - In a recent Cognition paper (Cognition 85 (2002) B21), Bornkessel, Schlesewsky,
      and Friederici report ERP data that they claim "show that online processing
      difficulties induced by word order variations in German cannot be attributed to
      the relative infrequency of the constructions in question, but rather appear to
      reflect the application of grammatical principles during parsing" (p. B21). In
      this commentary we demonstrate that the posited contrast between grammatical
      principles and construction (in)frequency as sources of parsing problems is
      artificial because it is based on factually incorrect assumptions about the
      grammar of German and on inaccurate corpus frequency data concerning the German
      constructions involved.

PMID- 14599757
TI  - ERP correlates of auditory negative priming.
AB  - Negative priming refers to slowed down reactions when the distractor on one trial
      becomes the target on the next. Following two popular accounts, the effect might
      be due either to inhibitory processes associated with the frontal cortex, or to
      an ambiguity in the retrieval of episodic information. We used event-related
      brain potentials (ERPs) to identify the processing stage primarily associated
      with negative priming. In an auditory categorization task, reactions in negative
      priming trials were compared to reactions in a standard control (unrelated primes
      and probes) and a repetition control (attended prime=ignored probe) condition.
      Reactions were slower for negative priming than for standard control (Delta32 ms)
      and repetition control trials (Delta64 ms). The corresponding ERP effect was
      reflected in an attenuation of a sustained parietal positivity extending from 300
      to 600 ms. Because corresponding ERP components were found to be sensitive to
      stimulus recognition and familiarity, the results may be interpreted to support
      an episodic retrieval account of negative priming.

PMID- 14599758
TI  - Are children moral objectivists? Children's judgments about moral and response
      dependent properties.
AB  - Researchers working on children's moral understanding maintain that the child's
      capacity to distinguish morality from convention shows that children regard moral
      violations as objectively wrong (e.g. Nucci, L. (2001). Education in the moral
      domain. Cambridge: Cambridge University Press). However, one traditional way to
      cast the issue of objectivism is to focus not on conventionality, but on whether
      moral properties depend on our responses, as with properties like icky and fun.
      This paper argues that the moral/conventional task is inadequate for assessing
      whether children regard moral properties as response-dependent. Unfortunately,
      children's understanding of response-dependent properties has been neglected in
      recent research. Two experiments are reported showing that children are more
      likely to treat properties like fun and icky as response-dependent than moral
      properties like good and bad. Hence, this helps support the claim that children
      are moral objectivists.

PMID- 14599759
TI  - Identifying airway sensitizers: cytokine mRNA profiles induced by various
      anhydrides.
AB  - Exposure to low molecular weight (LMW) chemicals in the workplace has been linked
      to a variety of respiratory effects. Within the LMW chemicals, one of the major
      classes involved in these effects are the acid anhydrides. The immunological
      basis of respiratory hypersensitivity involves CD4+ cells. By virtue of their
      induction of cytokines typical of CD4+ T-helper type 2 (Th2) cells-interleukin
      (IL)-4, 10, and 13-respiratory sensitizers may be identified and differentiated
      from contact sensitizers which induce Th1 cytokines (IL-2 and IFN-gamma). Our
      previous work suggested that the ribonuclease protection assay (RPA) was useful
      in identifying the respiratory sensitizer, trimellitic anhydride (TMA), based on
      quantitative differences in Th2 cytokine mRNA as compared to the contact
      sensitizer dinitrochlorobenzene (DNCB). Therefore, the purpose of the studies
      described in this report was to expand the chemicals tested in the RPA. To this
      end, four acid anhydrides with known respiratory sensitization potential, TMA,
      maleic anhydride (MA), phthalic anhydride (PA) and hexahydrophthalic anhydride
      (HHPA), were tested. Although previously determined to induce immunologically
      equivalent responses in a local lymph node assay (LLNA), the initial dose chosen
      (2.5%) failed to induce Th2 cytokine mRNA expression. To determine if the lack of
      cytokine expression was related to dose, LLNAs were conducted at higher doses for
      each of the anhydrides. The highest doses evaluated (four- to six-fold higher
      than those used in the initial RPA) gave equivalent proliferative responses for
      the various anhydrides and were used for subsequent RPA testing. At these higher
      doses, significant increases in Th2 versus Th1 cytokine mRNA were observed for
      all anhydrides tested. These results suggest that the RPA has the potential to
      serve as a screen for the detection of LMW airway sensitizing chemicals. However,
      the basis for selecting immunologically equivalent doses may require some
      modification.

PMID- 14599760
TI  - Detection of systemic hypersensitivity to drugs using standard guinea pig assays.
AB  - The most commonly used assays designed to detect either skin or systemic immune
      based hypersensitivity reactions are those using guinea pigs (GP). We obtained
      data from various FDA records to evaluate the correlation between GP assay
      results and reported post-marketing systemic hypersensitivity reactions. We
      examined the new drug application (NDA) reviews of approved drugs for the results
      of GP assays. Post-marketing human data were extracted from the FDA adverse event
      reporting system (AERS). Drug usage data were obtained from a commercial database
      maintained by IMS Health Inc. We found 83 (21%) of 396 drugs approved between
      1978 and 1998 had reported GP test results. Among these 83 drugs, 14 (17%) were
      found to have positive results in at least one GP assay. Simple reporting index
      (RI) values for systemic hypersensitivity reactions were calculated from AERS
      data and usage to produce the index of adverse event reports per million shipping
      units of drug. A variety of definitions of positive human response were examined.
      A statistically significant association was seen for rash between post-marketing
      and clinical trials adverse event reports. No statistically significant
      associations between human data and GP test results were observed. These data
      suggest that standard GP assays have limited ability to predict human systemic
      hypersensitivity potential for pharmaceuticals.

PMID- 14599761
TI  - Chemical substances and contact allergy--244 substances ranked according to
      allergenic potency.
AB  - From 1985 to 2001 a group consisting of thirty experts including dermatologists
      from universities, representatives from the chemical industry and from regulatory
      authorities elaborated and consequently decided on the potency ranking of
      chemicals with contact allergenic properties. These chemicals were defined either
      as synthetic chemicals or as chemicals identified as ingredients in natural
      products. On 244 substances clinical and experimental data on humans and results
      of animal tests as documented in the scientific literature were carefully
      collected and evaluated. This careful evaluation and assessment of these
      chemicals clearly demonstrate that ranking of substances according to their
      allergenic potency is possible and justified. It was decided to rank the most
      potent contact allergens in Category A of substances having significant
      allergenic properties. Substances with a solid-based indication of a contact
      allergenic potential and substances with the capacity of cross-reactions were
      listed in Category B and substances with insignificant or questionable allergenic
      effects were listed in Category C. An assessment of these compiled data is
      published here. Three Appendices give a comprehensive overview of the 98
      substances listed in Category A, the 77 substances listed in Category B and the
      69 substances listed in Category C.

PMID- 14599762
TI  - Evaluation of hypersensitivity to anthraquinone-related substances.
AB  - Evaluation of hypersensitivity to anthraquinone dyes, which are widely used as
      color additives, was performed in guinea pigs. In animals sensitized with 1%
      commercial-grade D&C Green No. 6 (Quinizarin Green SS, CI61565), subsequent
      challenge with the same dye showed a dose-dependent hypersensitivity reaction,
      whereas challenge with D&C Green No. 6 purified by recrystallization did not.
      Guinea pigs sensitized with commercial-grade D&C Green No. 6 showed a positive
      reaction to challenge with quinizarin, an intermediate in dye synthesis, but not
      to p-toluidine, another intermediate. It was confirmed that quinizarin itself
      induced hypersensitivity. The cross-reactivity of four kinds of purified dyes, in
      which the quinizarin contents were 1.2ppm or less, was evaluated. Purified D&C
      Green No. 5 (Alizarin Cyanin Green F, CI61570), D&C Green No. 6 and Ext. D&C
      Violet No. 2 (Alizurol Purple, CI60730) did not produce a hypersensitivity
      response, while D&C Violet No. 2 (Alizurin Purple SS, CI60725) did. We found that
      D&C Green No. 5, D&C Green No. 6 and Ext. D&C Violet No. 2 do not intrinsically
      induce hypersensitivity, and we conclude that the reaction to challenge with the
      commercial-grade dyes is due to quinizarin contaminating them. In contrast, D&C
      Violet No. 2 per se induced hypersensitivity. A structure-activity study
      indicated that 1-hydroxyl and 4-hydroxyl groups in the anthraquinone structure
      are key factors in hypersensitivity induction by anthraquinone-related compounds.

PMID- 14599763
TI  - A flow-cytometric NK-cytotoxicity assay adapted for use in rat repeated dose
      toxicity studies.
AB  - A recent regulatory document for immunotoxicity testing of new pharmaceutical
      drugs includes cytotoxic natural killer (NK)-cell function as a required
      parameter in repeated dose toxicity studies. The classical 51Cr-release assay is
      the conventional test for cytotoxicity testing but several drawbacks with this
      assay has increased the demand for new reliable test systems.Here, we describe
      the optimisation of a flow-cytometric cytotoxicity assay especially adapted for
      regulatory rat studies in drug development. The test principle is based on target
      cell labelling with 5-(6)-carboxy-fluorescein succinimidyl ester (CFSE) and
      subsequent DNA-labelling with propidium iodide (PI) for identification of target
      cells with compromised cell membranes. The results are expressed as percentage of
      dead targets on a cell-to-cell basis. The final format of the assay includes
      0.5ml peripheral blood, 1.25x10(5) effector cells per sample, and collection of
      500 target events by flow-cytometry. When NKR-P1+ cells were removed from the
      effector cell population by magnetic depletion the relative proportion decreased
      from 6 to 0.08%. The corresponding cytotoxic activity decreased from 68 to 8%.
      Also, the cytotoxic activity showed a significant and positive correlation with
      the proportion of NK-cells present in the effector cell suspension. Thus, the
      cytotoxicity measured is almost exclusively exerted by NK-cells. The current flow
      cytometric test benefits from using peripheral blood as a source for effector
      cells since it will not conflict with the use of spleen for histopathological
      investigations in repeated dose toxicity studies. Additionally, since only a
      minimal number of effector cells are required per sample repeated testing of the
      same animal is enabled.

PMID- 14599764
TI  - On the 50th anniversary of the elucidation of the DNA structure.

PMID- 14599765
TI  - Mechanisms of human DNA repair: an update.
AB  - The human genome, comprising three billion base pairs coding for 30000-40000
      genes, is constantly attacked by endogenous reactive metabolites, therapeutic
      drugs and a plethora of environmental mutagens that impact its integrity. Thus it
      is obvious that the stability of the genome must be under continuous
      surveillance. This is accomplished by DNA repair mechanisms, which have evolved
      to remove or to tolerate pre-cytotoxic, pre-mutagenic and pre-clastogenic DNA
      lesions in an error-free, or in some cases, error-prone way. Defects in DNA
      repair give rise to hypersensitivity to DNA-damaging agents, accumulation of
      mutations in the genome and finally to the development of cancer and various
      metabolic disorders. The importance of DNA repair is illustrated by DNA repair
      deficiency and genomic instability syndromes, which are characterised by
      increased cancer incidence and multiple metabolic alterations. Up to 130 genes
      have been identified in humans that are associated with DNA repair. This review
      is aimed at updating our current knowledge of the various repair pathways by
      providing an overview of DNA-repair genes and the corresponding proteins,
      participating either directly in DNA repair, or in checkpoint control and
      signaling of DNA damage.

PMID- 14599766
TI  - Monitoring base excision repair by in vitro assays.
AB  - Base excision repair (BER) is the major mechanism for processing of mutagenic and
      genotoxic DNA base lesions caused by cellular environmental or exogenous
      mutagens. In vitro base excision repair assays have been used in studies aimed at
      understanding the nature of various human diseases, aging and mechanisms of
      genome recovery after mutagenic stress. This review describes the key base
      excision repair assays and addresses their advantages and limitations.

PMID- 14599767
TI  - Mammalian DNA base excision repair proteins: their interactions and role in
      repair of oxidative DNA damage.
AB  - The DNA base excision repair (BER) is a ubiquitous mechanism for removing damage
      from the genome induced by spontaneous chemical reaction, reactive oxygen species
      (ROS) and also DNA damage induced by a variety of environmental genotoxicants.
      DNA repair is essential for maintaining genomic integrity. As we learn more about
      BER, a more complex mechanism emerges which supersedes the classical, simple
      pathway requiring only four enzymatic reactions. The key to understand the
      complete BER process is to elucidate how multiple proteins interact with one
      another in a coordinated process under specific physiological conditions.

PMID- 14599768
TI  - APE/Ref-1 and the mammalian response to genotoxic stress.
AB  - Human apurinic/apyrimidinic endonuclease/redox factor-1 (hAPE/Ref-1) is a
      multifunctional protein involved in the repair of DNA damaged by oxidative or
      alkylating compounds as well as in the regulation of stress inducible
      transcription factors such as AP-1, NF-kappaB, HIF-1 and p53. With respect to
      transcriptional regulation, both redox dependent and independent mechanisms have
      been described. APE/Ref-1 also acts as a transcriptional repressor. Recent data
      indicate that APE/Ref-1 negatively regulates the activity of the Ras-related
      GTPase Rac1. How these different physiological activities of APE/Ref-1 are
      coordinated is poorly understood. So far, convincing evidence is available that
      the expression of the APE/Ref-1 gene is inducible by oxidative stress and that
      overexpressed APE/Ref-1 protein protects cells against the genotoxic and cell
      killing effects of reactive oxygen species (ROS), whereas down-regulation
      sensitizes cells. Therefore, APE/Ref-1 can be considered to be part of an
      adaptive cellular response mechanism to oxidative genotoxic stress. The
      physiological relevance of increase of either the repair or redox activity of
      APE/Ref-1 for this adaptive response is unclear. Data will be shown that
      transfection of the truncated protein exhibiting either one of the activities
      provoked increase of resistance. Since APE/Ref-1 expression level and
      intracellular localization is variable in different types of tumors and
      frequently found to be different in non-malignant compared to the corresponding
      malignant human tissue, the protein is thought to be a diagnostic and prognostic
      tumor marker. Because of its involvement in DNA repair and apoptosis-related
      signaling mechanisms, APE/Ref-1 is also being discussed as a novel target for
      tumor-therapeutic approaches.

PMID- 14599769
TI  - Nucleotide excision repair and its interplay with transcription.
AB  - Nucleotide excision repair (NER) is a multistep process capable to remove a
      variety of DNA distorting lesions from prokaryotic and eukaryotic genomes. In
      eukaryotic cells, the process requires more than 30 proteins to perform the
      different steps, i.e. recognition of DNA damage, single strand incisions and
      excision of the lesion-containing DNA fragment and DNA repair synthesis/ligation.
      NER can operate via two subpathways: global genome repair (GGR) and a specialized
      pathway coupled to active transcription (transcription-coupled repair, TCR) and
      directed to DNA lesions in the transcribed strand of active genes. Both in vivo
      as well as in cultured cells the fast removal of transcription blocking lesions
      by TCR is crucial to escape from lethal effects of inhibited transcription
      inhibition The most delicate step in NER is the recognition of the DNA lesions in
      their different chromatin context and the mechanism of damage recognition in GGR
      and TCR is principally different and requires specific proteins. In GGR, the XPC
      HR23B is essential for the formation of the incision complex. In TCR the Cockayne
      syndrome (CS) gene products are key players in the recognition of a stalled RNA
      polymerase the presumed signaling structure for repair of transcribed strands. In
      this study, we show that the extent of recovery of UV-inhibited transcription and
      TCR strictly depends on the amount of CSB protein as well as the amount of DNA
      damage present in the cell. This indicates that the ratio between DNA damage
      frequency and CSB protein concentration in the cell is rather critical for acute
      cellular response, i.e. recovery of inhibited transcription upon DNA damage
      infliction, and hence cellular survival.

PMID- 14599770
TI  - Homologous recombination and cell cycle checkpoints: Rad51 in tumour progression
      and therapy resistance.
AB  - We provide an overview of the functional interrelationship between genes and
      proteins related to DNA repair by homologous recombination and cell cycle
      regulation in relation to the progression and therapy resistance of human
      tumours. To ensure the high-fidelity transmission of genetic information from one
      generation to the next, cells have evolved mechanisms to monitor genome
      integrity. Upon DNA damage, cells initiate complex response pathways including
      cell cycle arrest, activation of genes and gene products involved in DNA repair,
      and under some circumstances, the triggering of programmed cell death.
      Deregulation of this co-ordinated response leads to genetic instability and is
      fundamental to the aetiology of human cancer. Homologous recombination involved
      in DNA repair is induced by environmental damage as well as misreplication during
      the normal cell cycle. However, when not regulated properly, it can result in the
      loss of heterozygocity or genetic rearrangements, central to the process of
      carcinogenesis. The central step of homologous recombination is the DNA strand
      exchange reaction catalysed by the eukaryotic Rad51 protein. Here, we describe
      the recent progress in our understanding of how Rad51 is involved in the
      signalling and repair of DNA damage and how tumour suppressors, such as p53, ATM,
      BRCA1, BRCA2, BLM and FANCD2 are linked to Rad51-dependent pathways. An increased
      knowledge of the role of Rad51 in DNA repair by homologous recombination and its
      effects on cell cycle progression, tumour development and tumour resistance may
      provide opportunities for identifying improved diagnostic markers and developing
      more effective treatments for cancer.

PMID- 14599771
TI  - Response to environmental carcinogens in DNA-repair-deficient disorders.
AB  - An increased mutation rate in human cells is a critical contributing factor for
      the development of malignancy. Many autosomal recessive genetic disorders are
      known, in which an increased mutation rate and predisposition for cancer can be
      attributed to a deficiency in DNA repair or associated processes. Some of these
      DNA repair deficiencies are manifested at the level of the mitotic chromosome as
      increased breakage, particularly after treatment with specific mutagens. The
      examination of the response of cells from patients with these disorders to
      carcinogens offers the opportunity to elucidate the mechanisms operating in human
      cells to combat DNA damage and mutation. Over the last few years, the underlying
      genes in many of these syndromes have been identified, enabling a much more
      detailed definition of the processes disturbed. This review concentrates on two
      of the chromosomal breakage syndromes, Fanconi anaemia and Nijmegen breakage
      syndrome, which have both distinct and common cellular features.

PMID- 14599772
TI  - Molecular mechanisms of individual radiosensitivity studied in normal diploid
      human fibroblasts.
AB  - The molecular mechanisms of individual radiosensitivity were studied in normal
      diploid human fibroblasts. For fibroblasts irradiated with X-rays in G1-phase the
      individual radiosensitivity was shown to be correlated with the extent of double
      strand break (dsb) repair. The number of residual dsbs (including both non- and
      mis-rejoined dsbs) varied between 2 and 5% of the initial number induced and was
      low for resistant and high for sensitive strains. In the G1-phase dsbs are
      considered to be mostly repaired via the non-homologous end-joining pathway
      (NHEJ). However, so far none of the parameters tested for this pathway was found
      to be correlated with the number of residual dsbs. The parameters tested were
      mRNA expression, protein level and localisation and activity of the DNA-PK, which
      is the central complex of NHEJ. The dsb-repair capacity is also not regulated by
      the differentiation status, which varies substantially among fibroblast strains,
      whereas there is some indication that dsb repair might depend on the chromatin
      structure, with more efficient repair in cells with condensed DNA. Residual dsbs
      are converted into lethal chromosome aberrations finally leading to the loss of
      clonogenic activity, when cells pass through mitosis. Beside this so-called
      mitotic death, X-irradiated human fibroblasts are also inactivated via the TP53
      dependent permanent G1-arrest, while apoptosis appears to be not important. On
      average, mitotic death and G1-arrest are equally effective, but there is a broad
      variation from one strain to the other, with a negative correlation between these
      two pathways. Fibroblast strains exhibiting only a moderate G1-arrest showed a
      high number of lethal aberrations and vice versa. This result points to a common
      regulator of both G1-arrest and dsb repair, which is presently under
      investigation.

PMID- 14599773
TI  - Reduced DNA double strand breaks in chlorambucil resistant cells are related to
      high DNA-PKcs activity and low oxidative stress.
AB  - Modulation of DNA repair represents a strategy to overcome acquired drug
      resistance of cells to genotoxic chemotherapeutic agents, including nitrogen
      mustards (NM). These agents induce DNA inter-strand cross-links, which in turn
      produce double strand breaks (dsbs). These breaks are primarily repaired via the
      nonhomologous end-joining (NHEJ) pathway. A DNA-dependent protein kinase (DNA-PK)
      complex plays an important role in NHEJ, and its increased level/activity is
      associated with acquired drug resistance of human tumors. We show in this report
      that the DNA-PK complex has comparable levels and kinase activity of DNA-PK
      catalytic subunit (DNA-PKcs) in a nearly isogenic pair of drug-sensitive (A2780)
      and resistant (A2780/100) cells; however, treatment with chlorambucil (Cbl), a NM
      type of drug, induced differential effects in these cells. The kinase activity of
      DNA-PKcs was increased up to 2h after Cbl treatment in both cell types; however,
      it subsequently decreased only in sensitive cells, which is consistent with
      increased levels of DNA dsbs. The decreased kinase activity of DNA-PKcs was not
      due to a change in its amount or the levels of Ku70 and Ku86, their subcellular
      distribution, cell cycle progression or caspase-mediated degradation of DNA-PK.
      In addition to DNA cross-links, Cbl treatment of cells causes a 2.2-fold increase
      in the level of reactive oxygen species (ROS) in both cell types. However, the
      ROS in A2780/100 cells were reduced to the basal level after 3-4h, while
      sensitive cells continued to produce ROS and undergo apoptosis. Pre-treatment of
      A2780 cells with the glutathione (GSH) precursor, N-acetyl-L-cysteine prevented
      Cbl-induced increase in ROS, augmented the kinase activity of DNA-PKcs, decreased
      the levels of DNA dsbs and increased cell survival. Depletion in GSH from
      A2780/100 cells by L-buthionine sulfoximine (BSO) resulted in sustained
      production of ROS, lowered DNA-PKcs kinase activity, enhanced levels of DNA dsbs,
      and increased cell killing by Cbl. We propose that oxidative stress decreases
      repair of DNA dsbs via lowering kinase activity of DNA-PKcs and that induction of
      ROS could be the basis for adjuvant therapies for sensitizing tumor cells to
      nitrogen mustards and other DNA cross-linking drugs.

PMID- 14599775
TI  - Modulation of DNA repair processes by arsenic and selenium compounds.
AB  - Nickel, cadmium, cobalt and arsenic compounds are well known carcinogens to
      humans and experimental animals. In addition to the induction of mainly oxidative
      DNA damage, they interfere with nucleotide and base excision repair (BER) at low,
      non-cytotoxic concentrations. In case of arsenic, an inactivation of DNA repair
      has also been observed for the trivalent and pentavalent methylated metabolites,
      with the strongest effects exerted by MMA(III) and DMA(III). As potential
      molecular targets, interactions with so-called zinc finger proteins involved in
      DNA repair and/or DNA damage signaling have been identified. For example,
      arsenite suppresses poly(ADP-ribosyl)ation at extremely low, environmentally
      relevant concentrations. Also, Fpg and XPA involved in BER and NER, respectively,
      are inactivated by arsenite, MMA(III) and DMA(III). Nevertheless, an interaction
      with the zinc finger structures of DNA repair proteins may also occur by
      essential trace elements such as certain selenium compounds, which appear to
      exert anticarcinogenic properties at low concentrations but may compromise
      genetic stability at higher concentrations.

PMID- 14599774
TI  - Inhibition of DNA repair by Pentoxifylline and related methylxanthine
      derivatives.
AB  - The methylxanthine drug Pentoxifylline is reviewed for new properties which have
      emerged only relatively recently and for which clinical applications can be
      expected. After a summary on the established systemic effects of Pentoxifylline
      on the microcirculation and reduction of tumour anoxia, the role of the drug in
      the treatment of vasoocclusive disorders, cerebral ischemia, infectious diseases,
      septic shock and acute respiratory distress, the review focuses on another level
      of drug action which is based on in vitro observations in a variety of cell
      lines. Pentoxifylline and the related drug Caffeine are known radiosensitizers
      especially in p53 mutant cells. The explanation that the drug abrogates the G2
      block and shortens repair in G2 by promoting early entry into mitosis is not
      anymore tenable because enhancement of radiotoxicity requires presence of the
      drug during irradiation and fails when the drug is added after irradiation at the
      G2 maximum. Repair assays by measurement of recovery ratios and by delayed
      plating experiments indeed strongly suggested a role in repair which is now
      confirmed for Pentoxifylline by constant field gel electrophoresis (CFGE)
      measurements and for Pentoxifylline and for Caffeine by use of a variety of
      repair mutants. The picture now emerging shows that Caffeine and Pentoxifylline
      inhibit homologous recombination by targeting members of the PIK kinase family
      (ATM and ATR) which facilitate repair in G2. Pentoxifylline induced repair
      inhibition between irradiation dose fractions to counter interfraction repair has
      been successfully applied in a model for stereotactic surgery. Another realistic
      avenue of application of Pentoxifylline in tumour therapy comes from experiments
      which show that repair events in G2 can be targeted directly by addition of
      cytotoxic drugs and Pentoxifylline at the G2 maximum. Under these conditions
      massive dose enhancement factors of up to 80 have been observed suggesting that
      it may be possible to realise dramatic improvements to tumour growth control in
      the clinic.

PMID- 14599778
TI  - Gene expression changes in MDBK cells infected with genotype 2 bovine viral
      diarrhoea virus.
AB  - Bovine viral diarrhoea viruses (BVDVs) are ubiquitous viral pathogens of cattle.
      These viruses exist as one of two biotypes, cytopathic and noncytopathic, based
      on the ability to induce cytopathic effect in cell culture. The noncytopathic
      biotypes are able to establish inapparent, persistent infections in both cell
      culture and in bovine foetuses of less than 150 days gestation. Interactions with
      the host cell and the mechanism by which viral tolerance is established are
      unknown. To examine the changes in gene expression that occur following infection
      of host cells with BVDV, serial analysis of gene expression (SAGE), a global gene
      expression technology was used. SAGE allows quantitation of virtually every
      transcript in a cell type without prior sequence information. Transcript
      expression levels and identities are determined by sequencing libraries composed
      of concatamers of 14 base DNA fragments (tags) derived from the 3'-end of each
      cellular mRNA transcript. Comparison of data obtained from uninfected and BVDV
      genotype 2-infected cell libraries revealed changes in gene expression associated
      with distinct biochemical pathways or functions. Isotypes of both alpha- and beta
      tubulins were down-regulated, indicating possible dysfunction in cell division
      and other functions where microtubules play a major role. Expression of genes
      encoding proteins involved in energy metabolism were expressed at essentially
      equivalent levels in both infected and uninfected cells. Genes encoding proteins
      involved in protein translation and post-translational modifications, functions
      necessary for viral replication, were generally up-regulated. These data indicate
      that following infection with BVDV, changes in gene expression occur that are
      beneficial for virus replication while having only minor changes in energy
      metabolism.

PMID- 14599776
TI  - Transgenic and knockout mice for DNA repair functions in carcinogenesis and
      mutagenesis.
AB  - Genetically modified mouse models with defects in DNA repair pathways, especially
      in nucleotide excision repair (NER) and mismatch repair (MMR), are powerful tools
      to study processes like carcinogenesis and mutagenesis. The use of mutant mice in
      these studies has many advantages over using normal wild type mice with respect
      to costs, number of animals, predictive value towards carcinogenic compounds and
      the duration of study. Short-term carcinogenicity assays still require
      considerable number of animals and extensive pathological analyses. Therefore,
      alternatives demanding less animals and shorter exposure times would be
      desirable. In this respect, one approach could be the use of transgenic mice
      harbouring marker genes, that can easily detect mutagenic features of
      carcinogenic compounds, especially when such models are in a DNA repair deficient
      background. Here, we review the progress made in the development and use of DNA
      repair deficient mouse models as replacements for long-term cancer assays and
      discuss the applicability of enhanced gene mutant frequencies as early indicators
      of tumourigenesis. Although promising models exist, there is still a need for
      more universally responding and highly sensitive mouse models, since it is likely
      that non-genotoxic carcinogens will go undetected in a DNA repair deficient
      mouse. One attractive candidate mouse model, having a presumptive broad detective
      range, is the Xpa/p53 mutant mouse model, which will be discussed in more detail.

PMID- 14599779
TI  - No caspase activation but overexpression of Bcl-2 in bovine cells infected with
      noncytopathic bovine virus diarrhoea virus.
AB  - Cytopathic bovine viral diarrhoea viruses (cp BVDV) induce apoptosis in
      permissible cell cultures via the intrinsic pathway, which involves the
      mitochondria as key organelles. An important event is the irreversible opening of
      the permeability transition pore (PTP) and the breakdown of the transmembrane
      potential DeltaPsi(m). The resulting release of cytochrome C from the
      mitochondria serves as a trigger to form the apoptosome which then leads to
      caspase activation and cell death. In contrast, noncytopathic (ncp) BVDV do not
      seem to affect cells in vivo or in vitro, suggesting that they inhibit apoptosis.
      Interestingly, inhibition of caspases in cells infected with cp BVDV delayed the
      apoptotic cascade but did not prevent the cytopathic effect (CPE). This suggests
      that the induction of apoptosis and the processes finally leading to the CPE may
      proceed separately, implying that the inhibition of apoptosis by ncp BVDV has to
      start earlier in the cascade. In this study we show that in fact apoptosis
      inhibition in cells infected with ncp BVDV must occur at the mitochondrial level,
      before the activation of the caspase cascade occurs. To elucidate the role of
      mitochondria after infection of cells with ncp BVDV, expression of Bcl-2 and Bax
      were analysed. It was shown that while Bax expression was not affected, the anti
      apoptotic Bcl-2 protein was upregulated, presumably suppressing initiation of
      cell death and enabling persistent infection in vitro.

PMID- 14599780
TI  - Genetic heterogeneity of bovine viral diarrhoea viruses from Spain.
AB  - Forty-four bovine viral diarrhoea virus (BVDV) isolates collected from the north
      of Spain between 1989 and 2000 were characterised at the molecular level. For 24
      of these isolates the entire N(pro) gene sequence was determined. Phylogenetic
      analysis revealed that 21 isolates belong to subgroup BVDV-1b, while two BVDV-1c
      isolates and one BVDV-1h isolate were found. Furthermore, 20 additional virus
      isolates were analysed by differential reverse transcription-polymerase chain
      reaction (RT-PCR) and classified as BVDV-1. The results from our study
      demonstrate that BVDV-1b is the most prevalent subgroup present in bovine dairy
      herds of Spain, while there is no evidence for the presence of BVDV-2.

PMID- 14599781
TI  - Aspects of the innate and adaptive immune responses to acute infections with
      BVDV.
AB  - The immune response can be divided into innate and adaptive components that
      synergise to effect the clearance of pathogens. Recently, it has been realised
      that these arms of the immune system do not act independently, the magnitude and
      quality of the adaptive response is dependent on signals derived from the innate
      response. Here, we review the innate immune responses to bovine viral diarrhoea
      virus infections of cattle and relate these changes to immunosuppression and the
      subsequent development of the adaptive immune response.

PMID- 14599782
TI  - Assessment of the use of gross lesions at post-mortem to detect outbreaks of
      classical swine fever.
AB  - The performance of pathological findings as a diagnostic tool for the detection
      of classical swine fever (CSF) outbreaks during the 1997/1998 CSF-epidemic in The
      Netherlands was evaluated by constructing and analysing receiver operating
      characteristic (ROC) curves. This was done at the individual pig level and at the
      submission level (a group of pigs from the same herd submitted together for post
      mortem investigation). At post-mortem examination, the tonsils, spleen, ileo
      caecal valve and renal pelvis were sampled, sent to the reference laboratory, and
      tested by means of a CSF-specific fluorescent antibody test in combination with a
      confirmatory test. This resulted in an infection status at the individual pig
      level. The infection status and pathological findings of 1072 individual pigs
      from a total of 230 infected herds were included in this analysis. We also
      included submissions of pigs from herds that were sent to post-mortem examination
      because of a clinically CSF-suspect situation but afterwards were concluded to be
      from non-infected herds. Infection status and pathological findings of 1224
      individual pigs from a total of 241 non-infected herds were included in the
      analysis. Pneumonia, pleuritis, chronic bronchitis, pulmonary oedema, chronic
      gastric ulceration, dry faecal contents in the colon, conjunctivitis,
      haemorrhages in the renal pelvis, renal haemorrhages, splenic enlargement,
      haemorrhages in the urinary bladder, haemorrhagic and enlarged lymph nodes were
      the most frequently recorded pathological findings during a post-mortem
      examination of pigs submitted in a CSF-suspect clinical situation. However, some
      of these pathological findings (e.g. pneumonia, pleuritis) were almost evenly
      distributed in infected and in non-infected pigs, resulting in a high sensitivity
      combined with a low specificity. The area under the ROC curve of pathological
      findings at the individual pig level and at the submission level was 0.720 and
      0.782, respectively, which was significantly (P<0.0001) larger than the area
      under the random ROC curve. It was concluded that, although gross pathology is a
      legitimate test, its quantitative contribution to the detection of CSF is
      limited.

PMID- 14599783
TI  - Use of an internal standard in a TaqMan nested reverse transcription-polymerase
      chain reaction for the detection of bovine viral diarrhoea virus.
AB  - The aim of this study was to improve molecular methods for the detection of
      bovine viral diarrhoea virus (BVDV). A single-tube nested reverse-transcriptase
      polymerase chain reaction (nRT-PCR) employing the 5'-3'-exonuclease assay
      (TaqMan) system was optimised for use with bulk milk, semen and whole blood
      samples. An artificial template (mimic) was engineered to provide in-tube
      validation of negative samples by demonstrating the absence of substances
      inhibitory to RT or PCR. This mimic was constructed by disrupting the BVDV
      amplicon at the TaqMan probe site by inserting a 295bp fragment of human genomic
      DNA. The mimic amplicon was discriminated from the BVDV RT-PCR products using a
      second TaqMan probe, with a different fluorochrome specific for the inserted DNA.
      This new method was more sensitive than BVDV antigen ELISA methods and the
      existing RT-PCR method used in the laboratory for detection of BVDV in bulk milk.
      Furthermore, RNA extracted by robotic methods has proved suitable for use in this
      assay. This TaqMan nRT-PCR will be a valuable method for the detection of BVDV in
      a variety of biological matrices including milk and semen.

PMID- 14599784
TI  - Vaccinology of classical swine fever: from lab to field.
AB  - There are two types of classical swine fever vaccines available: the classical
      live and the recently developed E2 subunit vaccines. The live Chinese strain
      vaccine is the most widely used. After a single vaccination, it confers solid
      immunity within a few days that appears to persist lifelong. The E2 subunit
      vaccine induces immunity from approximately 10-14 days after a single
      vaccination. The immunity may persist for more than a year, but is then not
      complete. The Chinese strain vaccine may establish a strong herd immunity 1-2
      weeks earlier than the E2 vaccine. The ability of the Chinese vaccine strain to
      prevent congenital infection has not been reported, but the E2 subunit vaccine
      does not induce complete protection against congenital infection. Immunological
      mechanisms that underlie the protective immunity are still to be elucidated. Both
      types of vaccine are considered to be safe. A great advantage of the E2 subunit
      vaccine is that it allows differentiation of infected pigs from vaccinated pigs
      and is referred to as a DIVA vaccine. However, the companion diagnostic E(rns)
      ELISA to actually make that differentiation should be improved. Many approaches
      to develop novel vaccines have been described, but none of these is likely to
      result in a new DIVA vaccine reaching the market in the next 5-10 years.
      Countries where classical swine fever is endemic can best control the infection
      by systematic vaccination campaigns, accompanied by the normal diagnostic
      procedures and control measures. Oral vaccination of wild boar may contribute to
      lowering the incidence of classical swine fever, and consequently diminishing the
      threat of virus introduction into domestic pigs. Free countries should not
      vaccinate and should be highly alert to rapidly diagnose any new outbreak. Once a
      new introduction of classical swine fever virus in dense pig areas has been
      confirmed, an emergency vaccination programme should be immediately instituted,
      for maximum benefit. The question is whether the time is ripe to seriously
      consider global eradication of classical swine fever virus.

PMID- 14599786
TI  - Stable expression of the avian retroviral oncoprotein v-Rel in avian, mouse, and
      dog cell lines.
AB  - Overexpression of the retroviral oncoprotein v-Rel can rapidly transform and
      immortalize a variety of avian cells in culture. However, mammalian models for v
      Rel-mediated oncogenesis have been compromised by the fact that high-level
      expression of v-Rel has been reported to be toxic in many mammalian cell types,
      including mouse 3T3 cells, Rat-1 cells, and mouse bone marrow cells. In this
      article, we demonstrate that 3T3 cells can support expression of v-Rel for at
      least 24 days when infected with a mouse stem cell virus (MSCV) retroviral vector
      containing v-rel. In retrovirus-infected 3T3 cells, v-Rel is located in the
      nucleus and can bind to DNA, but does not transform the cells. On the other hand,
      3T3 and Rat-2 cells do not express v-Rel after stable transfection with a pcDNA
      based v-Rel expression vector. We also show that infection of the IL3-dependent
      mouse B cell line BaF3 with the MSCV-v-rel vector results in expression of v-Rel,
      but does not convert these cells to growth factor independence. In contrast to
      3T3 cells, the dog osteosarcoma D17 cell line can support a high level of v-Rel
      expression, after either transfection or infection with a retroviral vector. That
      is, v-Rel can be stably expressed as a nuclear, DNA-binding protein in D17 cells
      to approximately the same level as in chicken embryo fibroblasts. These results
      suggest that the restriction to v-Rel expression in rodent fibroblasts is
      generally absent in D17 cells and that the type of v-rel expression vector
      determines whether 3T3 cells can support stable expression of v-Rel. The findings
      reported here are an essential first step in the development of mammalian systems
      to study Rel-mediated oncogenesis.

PMID- 14599785
TI  - Human rotavirus strains bearing VP4 gene P[6] allele recovered from asymptomatic
      or symptomatic infections share similar, if not identical, VP4 neutralization
      specificities.
AB  - A rotavirus VP4 gene P[6] allele has been documented in a number of countries to
      be characteristically associated with an endemic predominantly asymptomatic
      infection in neonates in maternity hospital nurseries. The mechanisms underlying
      the endemicity and asymptomatic nature of such neonatal infections remain
      unknown. Rotavirus strains sharing this same P genotype, however, have more
      recently been recovered from an increasing number of symptomatic diarrheal
      episodes in infants and young children in various parts of the world. Previously,
      we have shown that an asymptomatic P[6] rotavirus neonatal infection is not
      associated with a unique VP7 (G) serotype but may occur in conjunction with
      various G types. Although amino acid sequence comparisons of the VP4 gene between
      selected "asymptomatic" and "symptomatic" P[6] rotavirus strains have been
      reported and yielded information concerning their VP4 genotypes, serotypic
      comparisons of the outer capsid spike protein VP4 of such viruses have not been
      studied systematically by two-way cross-neutralizations. We determined the VP4
      neutralization specificities of four asymptomatic and four symptomatic P[6]
      strains: two each of asymptomatic and symptomatic strains by two-way tests, and
      two each of additional asymptomatic and symptomatic strains by one-way tests.
      Both asymptomatic and symptomatic P[6] strains were shown to bear similar, if not
      identical, VP4 neutralization specificities. Thus, P[6] rotavirus strains causing
      asymptomatic or symptomatic infections did not appear to belong to unique P (VP4)
      serotypes. In addition, a close VP4 serotypic relationship between human P[6]
      rotavirus strains and the porcine P[6] rotavirus Gottfried strain was confirmed.

PMID- 14599787
TI  - Evolution of coreceptor use and CD4-independence in envelope clones derived from
      SIVsm-infected macaques.
AB  - Coreceptor use of HIV can evolve during infection. We previously examined
      coreceptor use of related SIVsm inoculum viruses and sequential reisolates from
      cynomolgus macaques. These viruses exhibited broad coreceptor specificities and,
      generally, CCR5 use remained efficient and stable, while alternative coreceptor
      use decreased longitudinally. Here we demonstrate that individual envelopes
      (Envs) from inoculum and reisolate viruses fuse via a range of coreceptors,
      including CCR5, CCR8, CXCR6, GPR15, GPR1, and APJ. On the whole, coreceptor use
      of Envs from sequential reisolates recapitulated that of reisolate viruses, thus
      CCR5 use remained stable while alternative coreceptor use tended to decrease over
      time. Rhesus CCR5, GPR15, and CXCR6 supported fusion to a similar extent as their
      human counterparts. Additionally, a number of Envs mediated CD4-independent
      fusion via CCR5 and GPR15. Envs from different inoculum viruses exhibited
      distinct dependencies on CD4 for fusion via CCR5, ranging from strictly CD4
      dependent to efficiently CD4-independent. Early reisolates from macaques infected
      with CD4-independent inoculums maintained or evolved Envs with a broad range of
      CD4-independence. CD4-independence became less variable/efficient in late
      reisolates from macaques that developed neutralizing antibodies. Infection with a
      CD4-dependent virus resulted in evolution of CD4-independent Envs in late
      reisolates. While CD4 independence can potentially broaden tropism in vivo, CD4
      independent viruses are particularly sensitive to neutralizing antibodies.
      Therefore, interplay between receptor tropism and neutralization may shape viral
      evolution and SIV pathogenesis.

PMID- 14599788
TI  - The C-terminal half-fragment of the Sendai virus C protein prevents the gamma
      activated factor from binding to a gamma-activated sequence site.
AB  - Sendai virus C protein associates with the signal transducer and activator of
      transcription (STAT) 1 and inhibits the interferon (IFN) response. We report a
      molecular basis for the anti-IFN-gamma mechanism of Sendai virus. The C-terminal
      half-fragment of the C protein (D1) retains both the STAT1-binding and the anti
      IFN-gamma abilities comparable to those of the full-size C. IFN-gamma stimulation
      generates phosphorylated-STAT1 even in the presence of the C or the D1. The
      phosphorylated-STAT1 generated in the D1-expressing cells forms an aberrant
      complex, which does not bind to a gamma-activated sequence (GAS) probe. Purified
      D1, indeed, inhibits in vitro the binding of the phosphorylated-STAT1 dimer to
      the GAS probe. The D1, however, binds to the STAT1 N-terminal domain, but not the
      DNA binding domain. These results suggest the possibility that the C protein
      prevents the gamma-activated factor from binding to GAS elements through its
      interaction with the STAT1 N-terminal domain.

PMID- 14599789
TI  - Apoptosis induction and interferon signaling but not IFN-beta promoter induction
      by an SV5 P/V mutant are rescued by coinfection with wild-type SV5.
AB  - Infection of human cells with the paramyxovirus simian virus 5 (SV5) results in
      minimal cytopathic effect, and host interferon (IFN) and apoptotic pathways are
      not activated. We have previously shown that an rSV5 containing six naturally
      occurring P/V gene substitutions (rSV5-P/V-CPI-) displays premature and elevated
      expression of viral RNA and protein. In addition, cells infected with rSV5-P/V
      CPI- show induction of the IFN-beta promoter as well as activation of IFN
      signaling and apoptotic pathways. In this article, we have tested the hypothesis
      that rSV5-WT can supply trans-acting factors that prevent host cell antiviral
      responses induced by rSV5-P/V-CPI-. During coinfection of human A549 cells, rSV5
      WT blocked cell rounding, loss of cell volume, and DNA fragmentation induced by
      rSV5-P/V-CPI-, three later events in the apoptotic pathway, but was not able to
      block the loss of mitochondrial membrane potential (DeltaPsi(m)), an early event
      in the cell death process. As expected, IFN signaling was blocked during
      coinfections, and this was attributed to the loss of STAT1 induced by the rSV5-WT
      V protein. Surprisingly, simultaneous infection with rSV5-WT could not suppress
      the activation of the IFN-beta promoter by rSV5-P/V-CPI- infection. However, the
      IFN-beta promoter was not activated in cells that were first preinfected for 1 h
      with rSV5-WT and then subsequently infected with rSV5-P/V-CPI-. A model is
      proposed for activation of host responses to infection with the rSV5-P/V-CPI-
      mutant and the steps that are blocked by rSV5-WT.

PMID- 14599790
TI  - Neurovirulence of yellow fever 17DD vaccine virus to rhesus monkeys.
AB  - The yellow fever 17D virus is attenuated and used for human vaccination. Two of
      its substrains, 17D-204 and 17DD, are used for vaccine production. One of the
      remarkable properties of this vaccine is limited viral replication in the host
      but with significant dissemination of the viral mass, yielding a robust and long
      lived neutralizing antibody response. The vaccine has excellent records of
      efficacy and safety and is cheap, used as a single dose, and there are well
      established production methodology and quality control procedures which include
      the monkey neurovirulence test (MNTV). The present study aims at a better
      understanding of YF 17DD virus attenuation and immunogenicity in the MNVT with
      special emphasis on viremia, seroconversion, clinical and histological lesions
      scores, and their intrinsic variability across the tests. Several MNVTs were
      performed using the secondary seed lot virus 17DD 102/84 totaling 49 rhesus
      monkeys. Viremia was never higher than the accepted limits established in
      international requirements, and high levels of neutralizing antibodies were
      observed in all animals. None of the animals showed visceral lesions. We found
      that the clinical scores for the same virus varied widely across the tests. There
      was a direct correlation between the clinical scores in animals with clinical
      signs of encephalitis and a higher degree of central nervous system (CNS)
      histological lesions, with an increase of lesions in areas of the CNS such as the
      substantia nigra, nucleus caudatus, intumescentia cervicalis, and intumescentia
      ventralis. The histological scores were shown to be less prone to individual
      variations and had a more homogeneous value distribution among the tests. Since
      17DD 102/84 seed virus has been used for human vaccine production and
      immunization for 16 years with the vaccine being safe and efficacious, it
      demonstrates that the observed variations across the MNVTs do not influence its
      effect on humans.

PMID- 14599791
TI  - A viral transcriptional activator of Kaposi's sarcoma-associated herpesvirus
      (KSHV) induces apoptosis, which is blocked in KSHV-infected cells.
AB  - Replication and transcription activator (RTA), mostly encoded by Kaposi's sarcoma
      associated herpesvirus (KSHV) open reading frame 50, is expressed in the
      immediate-early phase of reactivation and plays a critical role in inducing the
      viral lytic cycle in KSHV-infected cells. We established cell clones from BJAB
      cells and replication-deficient BCBL-1 cells in which KSHV RTA expression was
      controlled by an inducible promoter of the tetracycline-based Tet-Off expression
      system. In RTA-inducible BJAB cells, tetracycline removal induced the synthesis
      of RTA, resulting in cell death. DNA fragmentation, structural changes in the
      cell membrane, and poly(ADP-ribose) polymerase (PARP) cleavage were observed in
      the RTA-induced BJAB cells, indicating that RTA expression induced caspase
      activation and cell death by apoptosis. However, expression of RTA in RTA
      inducible BCBL-1 cells did not undergo apoptosis and cell death. These results
      suggested that KSHV RTA is an apoptosis inducer that is opposed by an
      antiapoptotic pathway in infected cells.

PMID- 14599792
TI  - The E1A proteins of all six human adenovirus subgroups target the p300/CBP
      acetyltransferases and the SAGA transcriptional regulatory complex.
AB  - The N-terminal/conserved region 1 (CR1) portion of the human adenovirus (Ad) 5
      E1A protein was previously shown to inhibit growth in the simple eukaryote
      Saccharomyces cerevisiae. We now demonstrate that the corresponding regions of
      the E1A proteins of Ad3,-4,-9,-12, and -40, which represent the remaining five Ad
      subgroups, also inhibit yeast growth. These results suggest that the E1A proteins
      of all six human Ad subgroups share a common cellular target(s) conserved in
      yeast. Growth inhibition induced by either full-length or the N-terminal/CR1
      portion of Ad5 E1A was relieved by coexpression of the E1A binding portions of
      the mammalian p300, CBP, and pCAF acetyltransferases. Similarly, growth
      inhibition by the N-terminal/CR1 portions of the other Ad E1A proteins was
      suppressed by expression of the same regions of CBP or pCAF known to bind Ad5
      E1A. The physical interaction of each of the different Ad E1A proteins with CBP,
      p300, and pCAF was confirmed in vitro. Furthermore, deletion of the gene encoding
      yGcn5, the yeast homolog of pCAF and a subunit of the SAGA transcriptional
      regulatory complex, restored growth in yeast expressing each of the different Ad
      E1A proteins. This indicates that the SAGA complex is a conserved target of all
      Ad E1A proteins. Our results demonstrate for the first time that the p300, CBP,
      and pCAF acetyltransferases are common targets for the E1A proteins of all six
      human Ad subgroups, highlighting the importance of these interactions for E1A
      function.

PMID- 14599793
TI  - Deletions within the U3 long terminal repeat alter the tumorigenic potential of
      myeloblastosis associated virus type 1(N).
AB  - The molecularly cloned myeloblastosis-associated virus type-1(N) (MAV-1(N))
      strain induces specifically nephroblastomas in chicken. MAV-induced
      nephroblastoma constitutes a unique animal model of the human Wilms' tumor. We
      have previously shown that the MAV-1(N) long terminal repeats (LTR) were
      necessary and sufficient for nephroblastoma induction. Since major determinants
      for oncogenesis have been mapped in the U3 region of several other retroviruses,
      we have analyzed the tumorigenic potential of five recombinant viruses partially
      deleted in their U3 region. The results obtained indicated that deletions of the
      LTRs resulted in a modification of the pathogenic spectrum of MAV-1(N) and a
      decreased efficiency for nephroblastoma induction.

PMID- 14599794
TI  - Genomic sequence of a ranavirus (family Iridoviridae) associated with salamander
      mortalities in North America.
AB  - Disease is among the suspected causes of amphibian population declines, and an
      iridovirus and a chytrid fungus are the primary pathogens associated with
      amphibian mortalities. Ambystoma tigrinum virus (ATV) and a closely related
      strain, Regina ranavirus (RRV), are implicated in salamander die-offs in Arizona
      and Canada, respectively. We report the complete sequence of the ATV genome and
      partial sequence of the RRV genome. Sequence analysis of the ATV/RRV genomes
      showed marked similarity to other ranaviruses, including tiger frog virus (TFV)
      and frog virus 3 (FV3), the type virus of the genus Ranavirus (family
      Iridoviridae), as well as more distant relationships to lymphocystis disease
      virus, Chilo iridescent virus, and infectious spleen and kidney necrosis virus.
      Putative open reading frames (ORFs) in the ATV sequence identified 24 genes that
      appear to control virus replication and block antiviral responses. In addition,
      >50 other putative genes, homologous to ORFs in other iridoviral genomes but of
      unknown function, were also identified. Sequence comparison performed by dot plot
      analysis between ATV and itself revealed a conserved 14-bp palindromic repeat
      within most intragenic regions. Dot plot analysis of ATV vs RRV sequences
      identified several polymorphisms between the two isolates. Finally, a comparison
      of ATV and TFV genomic sequences identified genomic rearrangements consistent
      with the high recombination frequency of iridoviruses. Given the adverse effects
      that ranavirus infections have on amphibian and fish populations, ATV/RRV
      sequence information will allow the design of better diagnostic probes for
      identifying ranavirus infections and extend our understanding of molecular events
      in ranavirus-infected cells.

PMID- 14599795
TI  - Down-regulation of transcription of the proapoptotic gene BNip3 in cultured
      astrocytes by murine coronavirus infection.
AB  - Murine coronavirus mouse hepatitis virus (MHV) causes encephalitis and
      demyelination in the central nervous system of susceptible rodents. Astrocytes
      are the major target for MHV persistence. However, the mechanisms by which
      astrocytes survive MHV infection and permit viral persistence are not known. Here
      we performed DNA microarray analysis on differential gene expression in astrocyte
      DBT cells by MHV infection and found that the mRNA of the proapoptotic gene BNip3
      was significantly decreased following MHV infection. This finding was further
      confirmed by quantitative reverse transcription-polymerase chain reaction,
      Western blot analysis, and BNip3-promoter-luciferase reporter system.
      Interestingly, infection with live and ultraviolet light-inactivated viruses
      equally repressed BNip3 expression, indicating that the down-regulation of BNip3
      expression does not require virus replication and is mediated during cell entry.
      Furthermore, treatment of cells with chloroquine, which blocks the acidification
      of endosomes, significantly inhibited the repression of the BNip3 promoter
      activity induced by the acidic pH-dependent MHV mutant OBLV60, which enters cells
      via endocytosis, indicating that the down-regulation of BNip3 expression is
      mediated by fusion between viral envelope and cell membranes during entry.
      Deletion analysis showed that the sequence between nucleotides 262 and 550 of the
      588-base-pair BNip3 promoter is necessary and sufficient for driving the BNip3
      expression and that it contains signals that are responsible for MHV-induced down
      regulation of BNip3 expression in DBT cells. These results may provide insights
      into the mechanisms by which MHV evades host antiviral defense and promotes cell
      survival, thereby allowing its persistence in the host astrocytes.

PMID- 14599796
TI  - Characterization of novel recombinant HIV-1 genomes using the branching index.
AB  - We have characterized six novel genomes of human immunodeficiency virus type 1
      (HIV-1) sampled from individuals infected in Uganda and former Zaire. Four
      isolates (SE6954, SE8603, UG035, and UG266) had clear recombination patterns that
      included subtypes A1, D and C. The two remaining strains (SE8646 and SE9010) also
      appeared to be recombinant but had a more complex pattern. To facilitate the
      classification of these two genomes we developed a metric, the branching index,
      for characterization of "problematic" sequence fragments that associate to a
      subtype cluster with a high bootstrap value but are only distantly related to the
      reference sequences. The branching index is able to signal when parental
      representatives may be missing and a subtype classification thus is not
      meaningful. Several fragments of SE8646 and SE9010 had a branching index below
      the subtype defining cutoff value (0.55) and, therefore, these genomes could not
      be unequivocally classified. The branching index, with a cutoff value defined
      from analyses of HIV-1 reference sequences, may be a useful approach not only for
      more conservative classifications of HIV-1 subtypes but also for analyzing
      relationships among other types of sequences.

PMID- 14599797
TI  - Roles of outer capsid proteins as determinants of pathogenicity and host range
      restriction of avian rotaviruses in a suckling mouse model.
AB  - We previously demonstrated that a pigeon rotavirus, PO-13, but not turkey strains
      Ty-3 and Ty-1 and a chicken strain, Ch-1, induced diarrhea in heterologous
      suckling mice. In this study, it was suggested that these avirulent strains, but
      not PO-13, were inactivated immediately in gastrointestinal tracts of suckling
      mice when they were orally inoculated. To determine which viral proteins
      contribute to the differences between the pathogenicitiy and the inactivation of
      PO-13 and Ty-3 in suckling mice, six PO-13 x Ty-3 reassortant strains that had
      the genes of the outer capsid proteins, VP4 and VP7, derived from the opposite
      strain were prepared and were orally inoculated to suckling mice. A single strain
      that had both PO-13 VP4 and VP7 with the genetic background of Ty-3 had an
      intermediate virulence for suckling mice. Three strains with Ty-3 VP7, regardless
      of the origin of VP4, rapidly disappeared from gastrointestinal tracts of
      suckling mice. These results indicated that the difference between the
      pathogenicity of PO-13 and that of Ty-3 was mainly dependent on both their VP4
      and VP7. In particular, VP7 was found to be related to the inactivation of Ty-3
      in gastrointestinal tracts of suckling mice.

PMID- 14599798
TI  - Peptide domains involved in the localization of the porcine reproductive and
      respiratory syndrome virus nucleocapsid protein to the nucleolus.
AB  - The nucleocapsid (N) protein of porcine reproductive and respiratory syndrome
      virus (PRRSV) is the principal component of the viral nucleocapsid and localizes
      to the nucleolus. Peptide sequence analysis of the N protein of several North
      American isolates identified two potential nuclear localization signal (NLS)
      sequences located at amino acids 10-13 and 41-42, which were labeled NLS-1 and
      NLS-2, respectively. Peptides containing NLS-1 or NLS-2 were sufficient to
      accumulate enhanced green fluorescent protein (EGFP) in the nucleus. The
      inactivation of NLS-1 by site-directed mutagenesis or the deletion of the first
      14 amino acids did not affect N protein localization to the nucleolus. The
      substitution of key lysine residues with uncharged amino acids in NLS-2 blocked
      nuclear/nucleolar localization. Site-directed mutagenesis within NLS-2 identified
      the sequence, KKNKK, as forming the core localization domain within NLS-2. Using
      an in vitro pull-down assay, the N protein was able to bind importin-alpha,
      importin-beta nuclear transport proteins. The localization pattern of N-EGFP
      fusion peptides represented by a series of deletions from the C- and N-terminal
      ends of the N protein identified a region covering amino acids 41-72, which
      contained a nucleolar localization signal (NoLS) sequence. The 41-72 N peptide
      when fused to EGFP mimicked the nucleolar-cytoplasmic distribution of native N.
      These results identify a single NLS involved in the transport of N from the
      cytoplasm and into nucleus. An additional peptide sequence, overlapping NLS-2, is
      involved in the further targeting of N to the nucleolus.

PMID- 14599801
TI  - Genome sequence and organization of a nucleopolyhedrovirus isolated from the
      smaller tea tortrix, Adoxophyes honmai.
AB  - Adoxophyes honmai nucleopolyhedrovirus (AdhoNPV) has a distinctive pathology in
      A. honmai larvae, killing the host more slowly than other NPVs. To further
      understand the pathology of AdhoNPV, its genome was completely sequenced and
      compared with those of other baculoviruses. The AdhoNPV genome is 113,220 bp,
      with a G + C content of 35.6%. It contains 125 putative open reading frames
      (ORFs), of which 8 are unique to AdhoNPV, and 4 homologous regions. The other 117
      ORFs display similarity to previously characterized baculovirus genes involved in
      early and late gene expression, DNA replication, and structural and auxiliary
      functions. The phylogenetic position of AdhoNPV, in relation to 15 other
      baculoviruses whose genomes have been completely sequenced, was assessed by three
      different analyses: gene sequence, gene order, and gene content. Although gene
      content analysis failed to support the group II NPVs, phylogenetic trees based on
      gene sequence and gene order showed AdhoNPV to be closely related to the group II
      NPVs.

PMID- 14599800
TI  - Baculovirus virions displaying Plasmodium berghei circumsporozoite protein
      protect mice against malaria sporozoite infection.
AB  - The display of foreign proteins on the surface of baculovirus virions has
      provided a tool for the analysis of protein-protein interactions and for cell
      specific targeting in gene transfer applications. To evaluate the baculovirus
      display system as a vaccine vehicle, we have generated a recombinant baculovirus
      (AcNPV-CSPsurf) that displays rodent malaria Plasmodium berghei circumsporozoite
      protein (PbCSP) on the virion surface as a fusion protein with the major
      baculovirus envelope glycoprotein gp64. The PbCSP-gp64 fusion protein was
      incorporated and oligomerized on the virion surface and led to a 12-fold increase
      in the binding activity of AcNPV-CSPsurf virions to HepG2 cells. Immunization
      with adjuvant-free AcNPV-CSPsurf virions induced high levels of antibodies and
      gamma interferon-secreting cells against PbCSP and protected 60% of mice against
      sporozoite challenge. These data demonstrate that AcNPV-CSPsurf displays
      sporozoite-like PbCSP on the virion surface and possesses dual potentials as a
      malaria vaccine candidate and a liver-directed gene delivery vehicle.

PMID- 14599802
TI  - Promotion of retroviral entry in the absence of envelope protein by
      chlorpromazine.
AB  - Retrovirus packaging cell lines that express the Moloney murine leukemia virus
      gag, pol, and env genes and a retroviral vector genome can produce virus
      particles that are capable of transducing cells. Normally if the packaging cell
      line does not produce a functional viral fusion glycoprotein, such as the
      retroviral envelope protein or a foreign viral glycoprotein, then the viruses
      will be incapable of transducing cells. We have found that incubating envelope
      protein-deficient virus particles bound to cells with chlorpromazine leads to
      transduction. Chlorpromazine (CPZ) is a membrane-active reagent that is commonly
      used to induce the hemifusion to fusion transition when membrane fusion is
      mediated by partially defective viral glycoproteins. The concentration and pH
      dependence of the promotion of transduction by CPZ is consistent with a role for
      CPZ micelle formation in viral entry. These data indicate that caution is
      warranted when experiments concerning membrane fusion completion promoted by CPZ
      are analyzed.

PMID- 14599799
TI  - Differential multimerization of Moloney murine leukemia virus integrase purified
      under nondenaturing conditions.
AB  - Retroviral integrases (IN) catalyze the integration of the reverse-transcribed
      viral DNA into the host genome, an essential process leading to virus
      replication. For Moloney murine leukemia virus (M-MuLV) IN, the limited
      solubility of the recombinant protein has restricted the development of
      biophysical and structural analyses. Herein, recombinant M-MuLV IN proteins,
      either full length or two nonoverlapping domain constructs, were purified under
      non-denaturing conditions from solubilized bacterial extracts by Ni(2+)-NTA
      resins. Additionally, WT IN was further purified by heparin chromatography. All
      of the purified proteins were shown to be active and stable. WT M-MuLV IN
      chromatographed with a peak corresponding with a dimer by gel filtration
      chromatography. In contrast, the single point mutant C209A IN migrated
      predominantly as a tetramer. For both proteins, fractions in equilibrium between
      dimers and tetramers were competent to assemble concerted two-end integrations
      and yielded a unique strand-transfer profile in the presence of a 28-mer U5
      oligonucleotide substrate, indicative of a distinct conformation within the
      synaptic complex. This specific target-site selection was not observed with a
      shorter 20-mer U5 substrate. These studies provide the foundation for biophysical
      and structural analysis on M-MuLV IN and the mechanism of retroviral integration.

PMID- 14599803
TI  - A therapeutic strategy uses histone deacetylase inhibitors to modulate the
      expression of genes involved in the pathogenesis of rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is characterized by progressive destruction of the
      affected joints. The pathophysiology results from genetic susceptibility and
      autoimmune phenomena, leading to tissue inflammation and synovial hyperplasia
      termed pannus, which irreversibly destroys cartilage and bone. The current
      treatment options, which suppress immune responses or ameliorate inflammation, do
      not halt the destructive process. We found that the histone deacetylase (HDAC)
      inhibitors (phenylbutyrate and trichostatin A) causing histone hyperacetylation
      to modulate multiple gene expression not only induced the expression of p21(Cip1)
      and p16(INK4) in synovial cells but also inhibited the expression of tumor
      necrosis factor-alpha in affected tissues in adjuvant arthritis, an animal model
      of RA. Based on the observations that joint swelling is reduced, subintimal
      mononuclear cell infiltration is decreased, synovial hyperplasia is inhibited,
      pannus formation is suppressed, and no cartilage or bone destruction is seen, the
      HDAC inhibitors may represent a new class of compounds for the treatment of RA by
      simultaneously, coordinately, synergistically, or epigenetically modulating
      multiple molecular targets in the pathogenesis of RA.

PMID- 14599804
TI  - Improvement of skeletal lesions in mice with mucopolysaccharidosis type VII by
      neonatal adenoviral gene transfer.
AB  - Neonatal gene transfer using adenovirus vectors expressing human beta
      glucuronidase (AxCAhGUS) resulted in pathological improvement in multiple
      visceral organs of mice with mucopolysaccharidosis type VII (MPSVII). However,
      the therapeutic effect on skeletal deformities and growth retardation, the major
      clinical symptoms in MPSVII, was not fully investigated by biochemical and
      histopathological analyses. In this study, we injected AxCAhGUS into a murine
      model of MPSVII (B6/MPSVII) within 24 h of birth and evaluated the therapeutic
      effects on skeletal deformities and growth retardation. High levels of beta
      glucuronidase (GUSB) activity (approximately threefold higher than normal GUSB
      activity) were observed in the articular cartilage of the mice 30 days after the
      treatment. Histopathological study in the knee joints showed elimination of
      vacuole cells in the articular cartilage and growth plate. Subchondral bone near
      the articular surface was almost normal in the treated MPSVII mice. Long-term
      observation (for 140 days after treatment) indicated that characteristic
      phenotypes such as flattened face, hunched stature, and shortening of bone length
      in the treated mice were almost normal. These results demonstrate that a single
      injection of adenovirus vector into neonatal MPSVII mice is sufficient for long
      term normalization of skeletal deformities and effective in pathological
      correction of the articular cartilage and growth plate.

PMID- 14599806
TI  - Electrochemo-gene therapy of cancer: intratumoral delivery of interleukin-12 gene
      and bleomycin synergistically induced therapeutic immunity and suppressed
      subcutaneous and metastatic melanomas in mice.
AB  - To treat established melanoma in mice, intratumoral transfer of bleomycin and/or
      an interleukin (IL)-12 expression vector was performed by means of
      electroporation. Although either bleomycin alone or the IL12 gene alone
      significantly suppressed the subcutaneous tumors, the combination therapy
      drastically improved the therapeutic outcome. Three of eight mice (37.5%) that
      received both bleomycin and the IL12 gene showed complete remission of the
      preestablished tumors and rejected subsequent rechallenge with the tumor cells.
      We also examined whether electrochemo-gene therapy for subcutaneous tumor mass
      induced suppression of pulmonary metastasis that had been established by
      intravenous inoculation of the melanoma cells. Although metastatic foci were
      significantly reduced in number in groups that were given IL12 gene alone or
      bleomycin plus IL12 gene, it was only the combination therapy that significantly
      prolonged the mean survival period of the tumor-bearing animals. Natural killer
      (NK) and cytotoxic T lymphocyte cytolytic activities were markedly enhanced in
      the mice that received the chemo-gene therapy, while IL12 gene therapy alone
      partially elevated the NK cytotoxicity. The present study suggests that the
      electroporation-mediated delivery of the IL12 gene and bleomycin synergistically
      elicits innate and adaptive anti-melanoma immune responses, resulting in marked
      suppression of the treated tumors as well as bystander metastatic lesions.

PMID- 14599805
TI  - Optimization of adenoviral vectors to direct highly amplified prostate-specific
      expression for imaging and gene therapy.
AB  - Gene expression-based imaging coupled to gene therapy will permit the prediction
      of therapeutic outcome. A significant challenge for successful gene therapy is to
      achieve a high-level of specific gene expression; however, tissue-specific
      promoters are weak. We postulate that if the weak activity of tissue-specific
      promoters can be amplified to the levels of strong viral promoters, which have
      been successful in preclinical scenarios, while retaining specificity, the
      therapeutic index of gene therapy can be greatly augmented. With this in mind, we
      developed a two-step transcriptional activation (TSTA) system. In this two-tiered
      system, a modified prostate-specific antigen promoter was employed to drive a
      potent synthetic transcriptional activator, GAL4-VP2. This, in turn, activated
      the expression of a GAL4-dependent reporter or therapeutic gene. Here we
      demonstrate that recombinant adenoviral vectors (Ads) in which we have
      incorporated prostate-targeted TSTA expression cassettes retain cell specificity
      and androgen responsiveness in cell culture and in animal models, as measured by
      noninvasive optical bioluminescence imaging. We investigated the mechanism of
      TSTA in different adenoviral configurations. In one configuration, both the
      activator and the reporter components are inserted into a single Ad (AdTSTA-FL).
      The activity of AdTSTA-FL exceeds that of a cytomegalovirus promoter-driven
      vector (AdCMV-FL), while maintaining tissue specificity. When the activator and
      reporter components are placed in two separate Ads, androgen induction is more
      robust than for the single AdTSTA-FL. Based on these findings, we hope to refine
      the TSTA Ads further to improve the efficacy and safety of prostate cancer gene
      therapy.

PMID- 14599807
TI  - The effect of sequestration by nontarget tissues on anti-tumor efficacy of
      systemically applied, conditionally replicating adenovirus vectors.
AB  - Avoiding transduction of normal tissue after intravenous application of oncolytic
      adenoviruses (Ad) is an important strategy to improve the safety and efficacy of
      these vectors in gene therapy. As a model for a targeted vector, we used Ad
      vectors with type 35 fibers (Ad5/35), which efficiently transduce human cervical
      carcinoma cells but not liver cells. In an in vitro model of liver metastases, in
      which small nests of HeLa cells were surrounded by mouse hepatocytes, we showed
      that an Ad5/35-based conditionally replicating vector regulated by DNA
      replication-dependent recombination conferred increased gene transfer to tumor
      cells and enhanced viral replication and tumor cell lysis compared to the
      nontargeted Ad5 vector. Intravenous injection of Ad5/35 vectors into mice bearing
      liver metastases derived from HeLa cells caused markedly less hepatotoxicity than
      Ad5 vectors; however, it did not result in enhanced tumor cell transduction,
      viral replication, or oncolysis. Apparently, other factors, including the
      stability of virus in the blood, trapping within the liver sinusoids,
      transendothelial transfer, and/or vector diffusion of viral particles to tumor
      cells, limit tumor transduction, even if the vector is not taken up by liver
      cells.

PMID- 14599808
TI  - MLV/HIV-pseudotyped vectors: a new treatment option for cutaneous T cell
      lymphomas.
AB  - Cutaneous T cell lymphomas (CTCLs) are lymphoproliferative disorders involving
      the skin. Malignant cells have a CD4+ T-helper phenotype and are found in early
      stages of the disease in plaques and cutaneous tumors. MLV/HIV-pseudotyped
      retroviral vectors target gene transfer to CD4-positive T cells and are therefore
      well suited to be specific delivery vehicles to treat CTCLs. We established a
      mouse xenograft model for CTCL and generated MLV/HIV-pseudotyped vectors encoding
      the herpes simplex virus thymidine kinase (HSV-TK), a well-known suicide gene, to
      prove the efficacy of MLV/HIV vectors in CTCL treatment. Vector particles were
      intratumorally injected into CTCL nude mouse xenografts. Mice were systemically
      treated with ganciclovir (GCV) and the tumor tissue was analyzed. A significant
      delay in tumor growth was observed for HSV-TK-transduced and GCV-treated tumors.
      GFP expression could be detected exclusively in CD4+ cells of tumors after
      transduction with GFP-encoding control vectors. The data demonstrate a cell
      specific in vivo gene delivery via MLV/HIV-pseudotyped vectors and open new
      avenues for the treatment of CTCL in humans.

PMID- 14599809
TI  - In vitro and in vivo growth suppression of human papillomavirus 16-positive
      cervical cancer cells by E6 siRNA.
AB  - Human papillomavirus type 16 (HPV16), a causative agent of cervical cancers,
      encodes the E6 and E7 oncogenes, whose simultaneous expression is pivotal for
      malignant transformation and maintenance of malignant phenotypes. In the hope of
      developing a gene-specific therapy for HPV-related cancer, we examined the
      effects of E6 short-interfering RNA (siRNA) on the expression of these oncogenes
      and on the cell growth of HPV16-related cervical cancer cells. Using SiHa
      cervical cancer cells, we demonstrated that E6 siRNA decreased the levels of mRNA
      encoding E6 as well as that encoding E7 protein and also induced nuclear
      accumulation of p53, the most important target of E6. E6 siRNA suppressed
      monolayer and anchorage-independent growth of SiHa cells, which was associated
      with p21(CIP1/WAF1) induction and hypophosphorylation of retinoblastoma protein.
      Further, SiHa cells treated with E6 siRNA formed tumors in NOD/SCID mice that
      were significantly smaller than in those treated with control siRNA. Our results
      show HPV E6 siRNA as a candidate for gene-specific therapy for HPV-related
      cervical cancer.

PMID- 14599810
TI  - Small interfering RNA inhibits hepatitis B virus replication in mice.
AB  - Current therapies for chronic hepatitis B virus (HBV) infection are limited in
      their effect on viral gene expression and replication. Recent reports have shown
      that RNA interference can be induced in mammalian cells by short interfering RNA
      duplexes (siRNA). Here we studied the effects of an HBV-specific 21-bp siRNA
      targeted to the surface antigen region (HBsAg), where three major viral mRNAs
      overlap, on HBV gene expression and replication both in a cell culture system and
      in a mouse model for HBV replication. Transfection of siRNA into HepG2.2.15
      cells, which constitutively produce HBV particles, caused a significant reduction
      in viral RNA production that was accompanied by a >80% drop in the secretion of
      viral HBsAg and HBeAg into the medium. The effect of RNAi was tested in vivo in a
      mouse model that we have developed for HBV infection, which entails hydrodynamic
      injection of a plasmid bearing the HBV genome into tail veins of mice. Injection
      of the HBV plasmid induces viral replication and generation of HBV viral
      particles detectable in the mouse sera. Co-injection of the HBV plasmid together
      with siRNA caused a significant inhibition in the level of viral transcripts,
      viral antigens, and viral DNA detected in the livers and sera of the treated mice
      relative to control animals. Results suggest that siRNA is capable of inhibiting
      HBV replication in vivo and thus may constitute a new therapeutic strategy for
      HBV infection.

PMID- 14599811
TI  - Lentiviral vectors pseudotyped with minimal filovirus envelopes increased gene
      transfer in murine lung.
AB  - A human immunodeficiency virus (HIV)-based vector pseudotyped with the Ebola
      Zaire (EboZ) viral envelope glycoprotein (GP) was recently shown to transduce
      murine airway epithelia cells in vivo. In this study, the vector was further
      redesigned to improve gene transfer and also to increase safety. We used mutant
      EboZ envelopes for pseudotyping, which resulted in higher titers and increased
      transduction of airway cells in vivo compared to vectors pseudotyped with wild
      type EboZ GP. As these envelopes lack regions associated with toxicity of the
      wild-type EboZ GP, they should also be safer to use for pseudotyping of
      lentiviral vectors. In addition, lentiviral vectors were created based on feline
      immunodeficiency virus and shown to have similar efficiency of transduction
      compared to HIV-based vectors. The creation of lentiviral vectors with highly
      engineered EboZ envelopes improved the performance of the system and should also
      increase its safety since only minimal regions of the EboZ envelope, which lack
      the toxic domain, are used.

PMID- 14599812
TI  - Transcriptional and posttranslational regulation of Cre recombinase by RU486 as
      the basis for an enhanced inducible expression system.
AB  - Genetic studies often require the employment of an inducible expression system,
      whereby the expression of a particular gene can be regulated by the exogenous
      administration of an inert ligand. Cre/loxP-based systems have been previously
      described as the basis for inducible expression systems by exerting site-specific
      DNA recombination. In our effort to enhance the properties of the RU486
      responsive CrePr1 construct, we have developed the dual GLVP/CrePr system, in
      which RU486 confers activity control at both the transcriptional and the
      posttranslational level of CrePr1. This was achieved by placing CrePr1
      transcriptional regulation under the control of the RU486-sensitive chimeric
      regulator GLVP. Stable cell lines harboring the dual GLVP/CrePr as well as the
      single CrePr1 system were developed. Our results indicate that the dually
      regulated system is highly inducible by RU486 while maintaining minimal basal
      activity ("leakage"), characteristics that can be employed in the development of
      transgenic mice in which genetic pathways can be turned on or turned off after
      exogenous administration of RU486 at physiologically inert doses.

PMID- 14599813
TI  - Engineered long terminal repeats of retroviral vectors enhance transgene
      expression in hepatocytes in vitro and in vivo.
AB  - To analyze the important elements for retroviral expression in hepatocytes, cis
      acting elements in the U3 region of the long terminal repeat (LTR) of the
      polycythemic strain of spleen focus-forming virus (SFFVp) were analyzed in a
      hepatocellular carcinoma cell line. Two cis-acting elements located within the
      upstream region of the direct repeat, which positively regulated retroviral
      expression, were identified. Transcription factors NFAT5 and Sp1, which are
      ubiquitously expressed in a variety of tissues, bound to these elements. To
      increase specificity without lowering the potency of retroviral expression in
      hepatocytes, these elements were replaced by a sequence derived from the
      hepatitis B virus enhancer II region. Novel vectors, SF-Hep3 and SF-Hep5 (SFFVp
      based vector for hepatocytes 3 and 5), were developed with these engineered LTRs.
      The engineered LTRs of these vectors enhanced the retroviral expression only in
      hepatocellular carcinoma cell lines in vitro. These vectors also increased
      transgene expression 4- to 9-fold or 3.5- to 5-fold in comparison with a Moloney
      murine leukemia virus-based vector or a vector containing the wild-type LTR of
      SFFVp, respectively, in murine hepatocytes in vivo.

PMID- 14599814
TI  - A stable murine-based RD114 retroviral packaging line efficiently transduces
      human hematopoietic cells.
AB  - Several barriers exist to high-efficiency transfer of therapeutic genes into
      human hematopoietic stem cells (HSCs) using complex oncoretroviral vectors. Human
      clinical trials to date have used Moloney leukemia virus-based amphotropic and
      gibbon ape leukemia virus-based envelopes in stable retroviral packaging lines.
      However, retroviruses pseudotyped with these envelopes have low titers due to the
      inability to concentrate viral supernatants efficiently by centrifugation without
      damaging the virus and low transduction efficiencies because of low-level
      expression of viral target receptors on human HSC. The RD114 envelope from the
      feline endogenous virus has been shown to transduce human CD34+ cells using
      transient packaging systems and to be concentrated to high titers by
      centrifugation. Stable packaging systems have potential advantages over transient
      systems because greater and more reproducible viral productions can be attained.
      We have, therefore, constructed and tested a stable RD114-expressing packaging
      line capable of high-level transduction of human CD34+ cells. Viral particles
      from this cell line were concentrated up to 100-fold (up to 10(7) viral
      particles/ml) by ultracentrifugation. Human hematopoietic progenitors from cord
      blood and sickle cell CD34+ cells were efficiently transduced with a Neo(R)
      containing vector after a single exposure to concentrated RD114-pseudotyped virus
      produced from this cell line. Up to 78% of progenitors from transduced cord blood
      CD34+ cells and 51% of progenitors from sickle cell CD34+ cells expressed the
      NeoR gene. We also show transfer of a human beta-globin gene into progenitor
      cells from CD34+ cells from sickle cell patients with this new RD114 stable
      packaging system. The results indicate that this packaging line may eventually be
      useful in human clinical trials of globin gene therapy.

PMID- 14599815
TI  - Characterization of in vitro and in vivo gene transfer properties of adenovirus
      serotype 35 vector.
AB  - We have recently developed a replication-defective, recombinant adenovirus (Ad)
      vector composed of the whole Ad serotype 35 (Ad35), a member of subgroup B. We
      describe herein the in vitro and in vivo gene transfer properties of Ad35 vector
      in comparison with Ad serotype 5 (Ad5) and the Ad5F35 vector, which is a fiber
      substituted Ad5 vector containing Ad35 fiber proteins. In vitro, Ad35 vector
      efficiently transduced not only human CAR-positive cells but also CAR-negative
      cells. Following intravenous administration into mice, both Ad5 and Ad35 vectors
      were rapidly cleared from the bloodstream with a half-life of approximately 3
      min. Ad5 vector-mediated transgene expression predominantly occurred in liver
      parenchymal cells, although the Ad5 vector was delivered to both liver
      parenchymal and nonparenchymal cells. In contrast, Ad35 vector was efficiently
      taken up by liver nonparenchymal cells and mediated transduction efficiency in
      the liver on a level 4 log orders lower than the Ad5 vector. These findings
      demonstrate that Ad35 vector is an attractive vehicle for gene transfer into
      human cells, while the biodistribution profile of Ad35 vector in mice is much
      different from that of the Ad5 vector.

PMID- 14599816
TI  - Rat strain differences in the ectopic osteogenic potential of recombinant human
      BMP adenoviruses.
AB  - Different animal strains have different genetic backgrounds that influence their
      physiological function and pathological process. The differences in genetic
      background may affect the efficiency of adenoviral infection and target gene
      expression and further cause different gene therapy results when target genes are
      delivered with adenoviral vectors. In this study, ectopic bone was not seen in
      ADCMVBMP4 injection sites, but was formed in ADCMVBMP9 injection sites in all rat
      strains. The mean volumes of bone induced with ADCMVBMP9 were 0.87 +/- 0.2 cm3 in
      Wistar, 0.26 +/- 0.1 cm3 in Long-Evans, 0.34 +/- 0.2 cm3 in Sprague-Dawley, 0.44
      +/- 0.1 cm3 in ACI, 0.66 +/- 0.2 cm3 in PVG, and 0.58 +/- 0.1 cm3 in Fischer 344
      rats. This indicates that ADCMVBMP9 has different bone formation potentials in
      different immunocompetent rat strains (P = 0.02). The basic levels of CD4+ and
      CD8+ T cells in blood before viral infection and titers of adenoviral
      neutralizing antibodies 30 days post-viral infection were significantly different
      among rat strains (P < 0.01). The efficiencies of target gene expression
      delivered with adenovirus were also significantly different in primary muscle
      cell cultures from different rat strains (P < 0.01). The different osteogenic
      potentials of ADCMVBMP9 among rat strains may be, in part, due to the differences
      in immune factors and target gene expression efficiency in muscle tissue.

PMID- 14599817
TI  - Certification assays for HIV-1-based vectors: frequent passage of gag sequences
      without evidence of replication-competent viruses.
AB  - A principal concern regarding the safety of HIV-1-based vectors is replication
      competent lentivirus (RCL). We have developed two PCR assays for detecting RCL;
      the first detects recombination between gag regions in the transfer vector and
      the packaging construct (sensitivity of detection approximately 10-100 copies of
      target sequence). The second assay uses real-time PCR to detect vesicular
      stomatitis virus glycoprotein (VSVG) envelope DNA (sensitivity approximately 5-50
      VSVG sequences). In an attempt to amplify any RCL, test vectors were used to
      transduce C8166 and 293 cells, which were then screened weekly for 3 weeks. Psi
      gag recombinants were routinely detected (20 of 21 analyses) in four
      transductions using the RRL-CMV-GFP vector. In contrast, VSVG sequences were
      detected only once in 21 analyses. Interestingly, p24 levels (as measured by
      ELISA) were occasionally detectable after 3 weeks of culture. To determine if a
      true RCL was present, 21-day cell-free medium was used to transduce naive cells.
      No evidence of psi-gag or VSVG transfer was detected, indicating that the
      recombination events were insufficient to reconstitute a true RCL. These findings
      have important implications for the design and safety of HIV-1-based vectors
      intended for clinical applications.

PMID- 14599818
TI  - VP22-mediated and light-activated delivery of an anti-c-raf1 antisense
      oligonucleotide improves its activity after intratumoral injection in nude mice.
AB  - VP22, a protein of the herpes simplex virus tegument, can form complexes with
      fluorescein-labeled oligonucleotides. These particles, termed "Vectosomes," are
      efficiently taken up by cells and remain stable in the cell cytoplasm without any
      particular activity. Interestingly, these Vectosomes can be disrupted by light,
      which releases the antisense activity. Here we show that anti-c-raf1 Vectosomes
      are efficiently activated by light in vivo after injection into subcutaneous A549
      (non-small-cell lung cancer) tumors implanted in nude mice. Moreover, two
      injections per week of anti-c-raf1 Vectosomes followed by illumination result in
      a stronger inhibition of tumor growth than injections of the antisense alone or
      of the different control Vectosomes. This effect correlates with a strong
      inhibition of the c-Raf1 protein expression. As a consequence of c-Raf1 loss,
      apoptosis was also detected in these tumors. Vectosomes thus represent a new
      powerful tool to improve the delivery of oligonucleotides in vitro and in vivo.

PMID- 14599819
TI  - Improved system for helper-dependent adenoviral vector production.
AB  - Helper-dependent adenoviral vectors (HDAds) are devoid of all viral coding
      sequences and have demonstrated tremendous potential for gene therapy by
      providing increased cloning capacity (up to 37 kb) and long-term, high-level
      transgene expression in vivo with negligible toxicity. Currently, the most widely
      used method of producing HDAds is the Cre/loxP system developed by Graham and co
      workers. However, two major obstacles currently hinder progress of this promising
      technology: (1) the difficulty of large-scale vector production and (2) helper
      virus (HV) contamination. We have developed an improved producer cell line, HV,
      and protocols that have successfully addressed these problems. With this system,
      >1 x 10(13) viral particles (vp) can be easily produced from 3 liters of cells
      within 2 weeks of vector rescue, with specific yields of >10,000 vp/cell and with
      exceedingly low HV contamination of 0.4-0.1% without relying on density-based
      vector purification and 0.02-0.01% following CsCl purification. This new system
      represents a major improvement over the original method in terms of simplicity,
      speed, vector yield, and purity, and it will significantly improve our ability to
      assess this promising gene therapy technology, especially in large animal models
      and, ultimately, for clinical applications.

PMID- 14599820
TI  - Baculovirus capsid display: a novel tool for transduction imaging.
AB  - Baculoviruses are enveloped insect viruses that can carry large quantities of
      foreign DNA in their genome. Baculoviruses have proved to be very promising gene
      therapy vectors but little is known about their transduction mechanisms in
      mammalian cells. We show in this study that Autographa californica multiple
      nuclear polyhedrosis virus capsid is compatible with the incorporation of desired
      proteins in large quantities. Fusions can be made to the N-terminus or C-terminus
      of the major capsid protein vp39 without compromising the viral titer or
      functionality. As an example of the baculovirus capsid display we show a tracking
      of the baculovirus transduction in mammalian cells by an enhanced green
      fluorescent protein (EGFP)-displaying virus. Our confocal and electron microscopy
      results suggest that the transduction block in mammalian cells is not in the
      endosomal escape, as previously proposed, but rather in the cytoplasmic transport
      or nuclear entry of the virus capsid. Our results also suggest that the EGFP
      tagged virus can be used for visualization of the virus biodistribution in vivo.
      Furthermore, capsid-modified baculoviruses hold great promise for the nuclear and
      subcellular targeting of transgenes and as a novel peptide display system for a
      variety of eukaryotic applications.

PMID- 14599821
TI  - Continuous local anaesthesia for post-operative mobilization of injured digits.
AB  - We have studied the effects of sustained local anaesthesia on postoperative
      mobilization of the injured hand. Small epidural catheters were placed adjacent
      to the peripheral nerves providing sensation to the involved part of the hand
      under direct vision in the distal forearm. Repeated doses of 0.5% bupivacaine
      were then administered during mobilization therapy to relieve pain. Fourteen out
      of 24 digits (60%) recorded 30 degrees or more increases in active range of
      motion after bupivacaine injection. The cases that failed to improve had suffered
      severe injuries. Complications were few and were easily managed as the catheters
      were distal, superficial and accessible. This is an effective, specific and safe
      method of providing sustained postoperative analgesia for mobilization.

PMID- 14599822
TI  - Non-vascularized free toe phalanx transfers in congenital hand deformities--the
      Great Ormond Street experience.
AB  - Many options of varying complexity are available for the management of congenital
      short digits resulting from aphalangia in symbrachydactyly and constriction ring
      syndrome. We have used non-vascularized free toe phalanx transfers for these
      children when a vascularized toe transfer has been contraindicated. We describe
      our technique and experience with 22 children who underwent a total of 64
      transfers of the proximal (35) or middle (29) toe phalanges (average 3 per
      child). The mean age at initial surgery was 15 months, and the mean follow-up was
      5 years. Duration of time until epiphyseal closure could not be determined
      accurately, but total digital elongation averaged 6mm. Complications of this
      technique include joint instability, premature epiphyseal closure and, in one
      patient, infection and graft loss. Donor site deformity was determined according
      to measured growth deficit and toe function. This technique is a simple option
      for digital elongation and, if performed in the appropriate age group in short
      fingered and monodactylous subtypes of symbrachydactyly, has the potential to
      allow growth and function with minimal donor site deficit.

PMID- 14599823
TI  - Skin tension in the aetiology of Dupuytren's disease; a prospective trial.
AB  - Tension in the palmar fascia has been proposed as a factor causing Dupuytren's
      disease. If tension does stimulate the growth of new Dupuytren's tissue,
      relieving longitudinal tension should reduce the recurrence rate following
      surgery. Thirty patients with palmar Dupuytren's contracture of a single ray that
      affected only the metacarpophalangeal joint were divided into two groups. Both
      groups had a fasciotomy: one group through a transverse incision that was closed
      directly and the other through a longitudinal incision with Z-plasty closure.
      Half the patients (seven of 14) who had direct closure had recurrence at 2 years
      as compared to two of the 13 in the Z-plasty group. The trial was stopped at the
      interim analysis stage due to the high recurrence rate in the first group. These
      results are consistent with the tension hypothesis for the aetiology of
      Dupuytren's disease.

PMID- 14599824
TI  - Functional outcome following extensor synovectomy and excision of the distal ulna
      in patients with rheumatoid arthritis.
AB  - We prospectively measured hand and wrist function in rheumatoid patients
      undergoing excision of the distal ulna. Range of motion, visual analogue pain
      scores and grip strength were measured in 22 wrists, and the Jebsen hand function
      test was administered to seven patients, preoperatively and at 3 and 12 months.
      At 1 year there were improvements in forearm pronation (P=0.04), supination
      (P=0.03) and wrist extension (P=0.02), but a reduction in flexion (P=0.009).
      Active radial deviation was reduced and ulnar deviation increased. There was a
      significant improvement in grip strength (P=0.05) and reduction in wrist pain
      (P=<0.0001). At 1 year the Jebsen hand function test showed improvements in
      simulated feeding, stacking checkers, and lifting large empty cans. Excision of
      the distal ulna in rheumatoid patients results in an improvement in some aspects
      of hand function.

PMID- 14599825
TI  - The shape of the triangular fibrocartilage during pronation-supination.
AB  - We studied the changes in the shape of the triangular fibrocartilage (TFC: disc
      proper) which occur during forearm rotation in disarticulated and articulated
      wrists. The influence of artificial 3mm ulnar lengthening on distortion of the
      disc was also examined. In the disarticulated wrists, slight distortion of the
      central and radial portions of the TFC was observed in the ulnar neutral variance
      specimens. More distortion was noted in the radial and central portions of the
      TFC in specimens with positive ulnar variance or with the ulna lengthened.
      However, in the articulated wrist, the TFC demonstrated little change in shape
      during pronosupination even in the ulnar positive variance wrists or with the
      ulna lengthened. There was no significant change in palmar and dorsal peripheral
      lengths of the TFC in ulnar neutral, ulnar positive or ulna-lengthened specimens
      at three rotatory positions of the forearm. These findings suggest that changes
      in ulnar variance which occur during forearm rotation can produce distortion on
      the TFC, but the carpus helps to maintain the shape of the TFC during pronation
      supination, even with positive ulnar variance.

PMID- 14599826
TI  - Suture anchor repair of ulnar-sided triangular fibrocartilage complex tears.
AB  - Traditional open repair of traumatic triangular fibrocartilage complex (TFCC)
      tears requires a relatively extensive exposure, and arthroscopic repair, though
      conceptually simple, can be technically demanding. We describe a mini-open suture
      anchor technique that, while minimally invasive, is easier to perform than
      previously described open or arthroscopic techniques. Results achieved using this
      technique in eight cases compare favourably with those reported for other
      techniques.

PMID- 14599827
TI  - Kinematics of ulnar head arthroplasty.
AB  - This in vitro study evaluated the performance of an ulnar head replacement. A
      joint simulator was employed that produced active forearm rotation in cadaveric
      specimens, with motion measured using an electromagnetic tracking system. The
      kinematics of the intact forearm were compared with a partial ulnar head
      replacement and a full replacement (with and without soft-tissue reconstruction)
      and a full excision of the ulnar head. There were no differences between intact
      kinematics and those following prosthetic reconstruction. However, ulnar head
      excision produced distal radioulnar joint instability in the form of radioulnar
      convergence and increased anteroposterior translations.

PMID- 14599828
TI  - Lessons learned from the management of complex intra-articular fractures at the
      base of the middle phalanges of fingers.
AB  - The use of dynamic traction splintage is established in the treatment of complex
      intra-articular phalangeal fractures. Several different systems have been used
      and we report our experience with one of these, the Pins and Rubber Traction
      System. A cohort of 14 patients with complex intra-articular fractures at the
      base of the middle phalanges of the fingers were treated and assessed
      prospectively over a 2.5-year period (mean, 20 months; range, 7-28 months). The
      mean active range of motion regained, at the proximal interphalangeal joint, was
      74 degrees (range, 0-100 degrees ). The mean total active motion of the injured
      digit was 196 degrees (range, 40-275 degrees ). Refinements in the regime are
      suggested as a result of this investigation.

PMID- 14599829
TI  - A comparative study between longitudinal and "T" incisions for dorsal plating of
      the distal radius.
AB  - A retrospective review of 24 patients with dorsal incisions for open reduction
      and internal fixation of Frykman VII/VIII distal radius fractures using a dorsal
      plate was performed. Half of them had a longitudinal incision while the other
      half had a T-shaped incision. No difference in the healing properties or wound
      morbidity could be demonstrated between the two groups. However, the T incision
      provided improved exposure of the distal radius and patient satisfaction with its
      cosmetic result was superior. The horizontal limb was well camouflaged within the
      transverse skin crease on the dorsal aspect of the wrist. The vertical limb did
      not extend into the dorsum of the hand and could, therefore, be hidden by
      appropriate clothing.

PMID- 14599830
TI  - Wrist arthrodesis using a Synthes wrist fusion plate.
AB  - Thirty-nine patients were retrospectively reviewed after a wrist arthrodesis
      using a Synthes wrist fusion plate and iliac crest bone graft. Information was
      obtained from review of patient files, a questionnaire to assess pain, function
      and work status, and clinical assessment of grip strength, forearm rotation and
      fingers motion. All wrist fusions united except that the index carpometacarpal
      joint failed to unite in one patient. Thirty-seven patients were satisfied with
      the procedure, noting a reduction in wrist pain after fusion, but all reported
      some limitation of function. The wrist fusion plate was removed in six patients
      and a further four patients experienced minor symptoms over the dorsal aspect of
      the middle finger metacarpal.

PMID- 14599831
TI  - Arthrodesis of the wrist for osteoarthritis: outcome with a minimum follow-up of
      4 years.
AB  - The outcome of total wrist arthrodesis was reviewed in 36 patients with
      osteoarthritis after a minimum follow-up of 4 years. Pain relief was not
      complete, and although 20 were pain free at rest, only six were pain-free during
      manual activity. Grip strength was 63% of the contralateral side and the DASH
      score remained high. Only 21 of the 34 could be re-employed. The mean time off
      work was 14 months. Complications were numerous and additional surgery was
      required in 21 patients.

PMID- 14599832
TI  - Results of ray resection and amputation for ring avulsion injuries at the
      proximal interphalangeal joint.
AB  - We investigated the long-term functional results of ray resection (14 cases) and
      amputation (nine cases) for ring avulsion injuries of ring finger which could not
      be replanted or underwent failed replantation. The mean follow-up was 37 (range,
      24-63) months in the ray resection group and 32 (range, 24-40) months in the
      amputation group. Grip strength, key pinch strength, chuck pinch strength, hand
      circumference and palmar volume were decreased in the ray resection group but
      only grip strength and pulp pinch strength were significantly decreased in the
      amputation group. These results suggest that ray resection should be avoided in
      patients with occupations that need strong key and chuck pinch functions.

PMID- 14599834
TI  - Trigger thumb: results of a prospective randomised study of percutaneous release
      with steroid injection versus steroid injection alone.
AB  - One hundred and twenty-seven trigger thumbs in 115 adult patients were randomised
      to either percutaneous release with steroid injection (n=66) or steroid injection
      alone (n=61). Two patients, one from each group, were lost to follow-up.
      Percutaneous release with steroid injection produced satisfactory results in 91%
      of cases whereas steroid injection alone produced satisfactory results in 47% of
      cases. One case in the percutaneous group developed stiffness and one in the
      injection group developed cellulitis. No digital nerve injury occurred in either
      group. We conclude that percutaneous trigger thumb release combined with steroid
      injection has a higher success rate than that of steroid injection alone.

PMID- 14599833
TI  - Fine needle aspiration cytology for soft tissue tumours of the hand.
AB  - The purpose of this study was to evaluate the usefulness of fine needle
      aspiration cytology for the preoperative diagnosis of soft tissue tumours of the
      hand. Fine needle aspiration cytology was performed on 93 soft tissue tumours of
      the hand which were classified as malignant, benign or unclassified based on
      cytological findings. We also attempted to make specific diagnosis by cytology.
      The cytological diagnosis was then compared with the postoperative
      histopathological diagnosis. The cytological differentiation between benign and
      malignant tumours showed neither false-positive nor false-negative results. Of
      the 47 lesions with sufficient material for cytology and that were
      postoperatively diagnosed histologically, 35 (including one recurrent lesion)
      were correctly diagnosed by fine needle aspiration cytology. No complications
      were encountered. Fine needle aspiration cytology has a high degree of diagnostic
      accuracy and safety for soft tissue tumours of the hand.

PMID- 14599835
TI  - Small joint fusion of the hand--a technique using Coughlin cup and cone reamers.
AB  - We describe a method of cup and cone arthrodesis using Coughlin concave and
      convex reamers, which we have used in a series of 22 hand joints in 19 patients.
      These reamers, originally designed for use in the foot, can be used in the hand
      to give very accurate preparation of bone surfaces. This results in maximum bone
      contact and the ability to fuse the joint in any desired position. The procedure
      is simple, rapid and forgiving. Union was achieved in all 22 cases, usually
      within 3 months.

PMID- 14599836
TI  - Assessment of results of opponensplasty.
AB  - One hundred and fifty-six opponensplasties carried out on 115 patients at
      Anandaban Hospital between 1987 and 1997 were reviewed. In most cases a flexor
      digitalis superficialis opponensplasty was performed. The outcome was assessed by
      measuring the finger to which the thumb could obtain a pinch grip, the gap
      between the thumb and little metacarpophalangeal joints, and the satisfaction of
      the patient. The objective assessments demonstrated excellent or good results in
      89%. Good or fair patient satisfaction was obtained in 93%. Early complications
      were seen in seven cases (4%). Objective measurements of outcome and patient
      satisfaction were not always in agreement, indicating that objective measures do
      not adequately assess the success of surgery from the patient's perspective. We
      thus conclude that subjective measurements of results are an important measure of
      success and should be included in the evaluation of surgical results.

PMID- 14599837
TI  - Comparative evaluation of effectiveness of different motor muscles in modified
      lasso procedure for correction of finger clawing.
AB  - A retrospective study was carried out to compare the effectiveness of different
      muscles as motors in modified lasso procedures for correction of finger clawing
      in leprosy. It was observed that palmaris longus and extensor carpi radialis
      longus were more suitable than the flexor digitorum superficialis. In some
      patients, removal of superficialis is associated with complications which could
      not be predicted before surgery. Extensor carpi radialis longus has advantages
      over palmaris longus in selected cases.

PMID- 14599838
TI  - Chondrosarcoma of small bones of the hand.
AB  - A clinicopathological review of 23 patients (mean age, 67 years; range, 42-85
      years) with chondrosarcoma of the bones of the hand was done. The mean follow up
      was 8.5 years. Eleven patients presented with a progressive painless swelling,
      26% having had symptoms for over 10 years. The proximal phalanx was the commonest
      site. Initial clinical misdiagnosis as ganglion, bursa, gout, rheumatoid
      arthritis and a cyst occurred in five patients. Radiologically most lesions
      showed bone expansion, cortical destruction and soft-tissue extension. The
      majority was of high histologic grade (Evan's grade 2 & 3) with extensive myxoid
      areas. Five out of eight patients who were originally treated by curettage or
      excision had local recurrences compared to none treated by ray resection or
      amputation of phalanx (P=0.002). None had metastases. The low risk of metastases
      despite the high histologic grade indicates that chondrosarcomas of the hand
      behave differently from chondrosarcomas elsewhere.

PMID- 14599842
TI  - Proceedings of the meeting of the Federation of Clinical Immunology Societies.
      May 15-19, 2003. Paris, France.

PMID- 14599840
TI  - Surgical treatment for cubital tunnel syndrome.

PMID- 14599843
TI  - Interphotoreceptor retinoid-binding protein (IRBP)-deficient C57BL/6 mice have
      enhanced immunological and immunopathogenic responses to IRBP and an altered
      recognition of IRBP epitopes.
AB  - Experimental autoimmune uveitis (EAU) and pinealitis (EAP) can be induced in
      susceptible mice by immunization with immunologically privileged retinal
      antigens. In the present study, we analyzed the immunologic and immunopathologic
      responses of mice deficient in the retinal autoantigen interphotoreceptor
      retinoid-binding protein (IRBP). The consequences of IRBP deficiency on the T
      cell repertoire were also investigated. IRBP+/+, IRBP+/- and IRBP-/- mice on the
      C57BL/6 background were immunized with IRBP or with a pathogenic epitope, IRBP(1
      20) peptide in adjuvant, and were evaluated for disease severity and
      immunological responses. C57BL/6 IRBP-/- mice were completely resistant to EAU
      and EAP, and had enhanced immunological responses to IRBP and to its pathogenic
      peptide 1-20, as compared to their IRBP+/+ counterparts. IRBP-/- mice exhibited
      an altered IRBP epitope recognition. T cell epitope mapping revealed a response
      to IRBP peptide 271-290 in IRBP-/- mice, that was absent in the wild type. Primed
      T cells of IRBP-/- mice transferred an exacerbated form of EAU to nai;ve wild
      type recipients. A gene-dose effect was evident in that C57BL/6 IRBP+/- mice,
      exhibited intermediate immunological responses and lower disease scores compared
      to wild type. We conclude that expression of IRBP in target tissues is a
      necessary prerequisite for disease induction, excluding other retinoid-binding or
      vision-related proteins as surrogate targets. Furthermore, endogenous expression
      of IRBP is directly responsible for lowering the threshold of susceptibility to
      uveitic disease.

PMID- 14599844
TI  - Characterization of HLA DR2 and DQ8 transgenic mouse with a new engineered mouse
      class II deletion, which lacks all endogenous class II genes.
AB  - Human autoimmune diseases are a class of complex immune system disorders
      characterized by loss of tolerance to self-antigens. HLA class II molecules play
      a central role in the initiation, propagation and prolongation of the disease
      process. HLA class II transgenic mice with mouse endogenous class II gene Ab
      knockout were used successfully in several mouse models for human autoimmune
      diseases, such as IDDM, SLE and EAE in our Lab. However, these mice carry the
      functional mouse Eb gene from the Abeta(0/0) construct and could express
      Ebeta/DRalpha(Ealpha) molecules and shape the T cell repertoire in these mice.
      Recently, we have obtained the new MHCII(Delta/Delta) mice that are devoid of all
      endogenous conventional mouse MHC class II genes. When these mice are mated with
      our HLA class II transgenic mice, only human class II genes are expressed. The DR
      and DQ molecules expressed in these mice shape the T cell repertoire and regulate
      the immune response. Therefore, this new class of HLA transgenic mice is the
      first to be completely "humanized" in their MHC class II genes and will be an
      invaluable mouse model for human MHC class II associated autoimmune diseases.

PMID- 14599845
TI  - Neonatal tolerance to a Th2-mediated autoimmune disease generates CD8+ Tc1
      regulatory cells.
AB  - Immunological tolerance can be achieved in animals by exposure of newborn to a
      foreign antigen. Depending on the dose and timing of the antigenic challenge,
      tolerance has been reported to result in clonal deletion, anergy or active
      suppression. In this latter case, regulatory T cells prevent autoimmunity by
      suppressing the reactivity of pathogenic self-reactive T cells. We have
      previously reported the generation of a neonatal, mercury-specific, and dominant
      tolerance to autoimmunity induced by mercury salts in rats. Chronic exposure to
      mercury salts can lead to SLE-like autoimmune responses, mediated by autoreactive
      CD4+ Th2 cells, that regulate and are followed by a resistant state mediated by
      protective CD8+ T cells. The aim of the study was to compare the resistance to
      the neonatal tolerance to mercury disease, and to further characterize the CD8+ T
      cells endowed with regulatory capacity in the neonatal tolerance model. We report
      here that resistance to mercury disease is long lasting and not mercury-specific,
      suggesting that different CD8+ T cells are involved in resistance and neonatal
      tolerance, and that regulatory CD8+ Tc1 cells generated in tolerance are required
      to control the CD8- cell population from developing Th2-mediated autoimmunity.
      Upon mercury recall, CD8+ CD45RC(high) T cells, that represent the Tc1 subset in
      the rat, expanded and were polarized towards IFNgamma production. Interestingly,
      identical results were obtained with the CD8+ CD25+T cell population. Substantial
      amounts of FasL gene expression were detected in CD8+ T lymphocytes upon recall
      with the tolerogen. AICD may be one of the regulatory mechanisms used by these
      regulatory CD8+ Tc1 cells that control neonatal tolerance to a Th2-mediated
      autoimmune disorder.

PMID- 14599846
TI  - Nondepleting anti-CD4 monoclonal antibody prevents diabetes and blocks induction
      of insulin autoantibodies following insulin peptide B:9-23 immunization in the
      NOD mouse.
AB  - INTRODUCTION: Insulin peptide B:9-23 is a major autoantigen in type 1 diabetes
      that induces insulin autoantibodies and prevents diabetes in the NOD. However,
      immunization with peptide without adjuvant may be insufficient to reverse disease
      or induce long-term tolerance. Furthermore, recent experience has demonstrated
      the potential dangers of disease exacerbation or anaphylaxis with peptide
      immunotherapy. METHODS: Combination therapy of B:9-23 with a nondepleting anti
      CD4 monoclonal antibody (YTS 177.9) was studied in female NOD mice from 4 through
      6 weeks of age. Injections of either B:9-23 in saline, YTS 177.9 antibody, or
      both peptide and antibody were given to mice. RESULTS: By 52 weeks follow-up, 40%
      of B:9-23-treated, 100% of YTS177.9-treated, and 70% of B:9-23 and YTS177.9
      combination-treated mice remained diabetes-free. IAA, both spontaneous and
      induced by B:9-23, was almost completely suppressed in mice receiving YTS 177.9.
      In addition to suppression of IAA expression, anti-B:9-23 peptide antibodies are
      also suppressed in mice receiving B:9-23 with YTS 177.9, compared to B:9-23
      alone. CONCLUSION: A brief course of the nondepleting anti-CD4 monoclonal
      antibody (YTS 177.9) in NOD mice confers long-term protection from diabetes and
      insulitis and profoundly blocks spontaneous and B:9-23 peptide-induced insulin
      autoantibodies.

PMID- 14599847
TI  - CD4+CD25+ regulatory T cells generated in response to insulin B:9-23 peptide
      prevent adoptive transfer of diabetes by diabetogenic T cells.
AB  - NOD mice have a relative deficiency of CD4+CD25+ regulatory T cells that could
      result in an inability to maintain peripheral tolerance. The aim of this study
      was to induce the generation of CD4+CD25+ regulatory T cells in response to
      autoantigens to prevent type 1 diabetes (T1D). We found that immunization of NOD
      mice with insulin B-chain peptide B:9-23 followed by 72 h in vitro culture with
      B:9-23 peptide induces generation of CD4+CD25+ regulatory T cells. Route of
      immunization has a critical role in the generation of these cells. Non-autoimmune
      mice BALB/c, C57BL/6 and NOR did not show up regulation of CD4+CD25+ regulatory T
      cells. These cells secreted large amounts of TGF-beta and TNF-alpha with little
      or no IFN-gamma and IL-10. Adoptive transfer of these CD4+CD25+ regulatory T
      cells into NOD-SCID mice completely prevented the adoptive transfer of disease by
      diabetogenic T cells. Although, non-self antigenic OVA (323-339) peptide
      immunization and in vitro culture with OVA (323-339) peptide does result in up
      regulation of CD4+CD25+ T cells, these cells did not prevent transfer of
      diabetes. Our study for the first time identified the generation of antigen
      specific CD4+CD25+ regulatory T cells specifically in response to immunization
      with B:9-23 peptide in NOD mice that are capable of blocking adoptive transfer of
      diabetes. Our results suggest the possibility of using autoantigens to induce
      antigen-specific regulatory T cells to prevent and regulate autoimmune diabetes.

PMID- 14599848
TI  - Lack of the mediators of innate immunity attenuate the development of autoimmune
      diabetes in mice.
AB  - Interleukin 15 (IL-15) and Interleukin 18 (IL-18) are key cytokines produced by
      macrophages during innate immune response. These cytokines can profoundly affect
      subsequent adaptive immune responses including autoimmunity. We have investigated
      the role of IL-15 and IL-18 in the development of autoimmune diabetes in mice
      induced by multiple low dose streptozotocin (MLD-STZ). To analyze the role of IL
      15, we tested the effects of a soluble murine IL-15 receptor alpha-chain (smIL
      15Ralpha), on the development of MLD-STZ in C57BL/6 mice. Animals were treated
      with 10 daily injections of 32 microg of smIL-15Ralpha starting on the first day
      of diabetes induction. This treatment significantly attenuated the development of
      diabetes as evaluated by significantly lower glycemia compared with control mice
      treated with an inactive mutant form of sIL-15Ra. To directly address the role of
      IL-18 in MLD-STZ we used IL-18 knockout (KO) mice on DBA/1 background. IL-18
      deficient mice were significantly more resistant to the induction of diabetes
      compared with the wild-type controls and did not develop the typical mononuclear
      cell infiltrates in the islets. Taken together our data suggest that the innate
      mediators, IL-15 and IL-18, are essential for the development of diabetes and may
      be important targets in prevention and early treatment of autoimmune diabetes.

PMID- 14599849
TI  - Anti-4-1BB-based immunotherapy for autoimmune diabetes: lessons from a transgenic
      non-obese diabetic (NOD) model.
AB  - Various therapeutic strategies have been developed to tolerize autoreactive T
      cells and prevent autoimmune pathology in type 1 diabetes. 4-1BB, a member of the
      tumor necrosis factor receptor (TNFR) superfamily, is a costimulatory receptor
      primarily expressed on activated T cells. The administration of an agonistic anti
      4-1BB antibody (2A) dramatically reduced the incidence and severity of
      experimental autoimmune encephalomyelitis (EAE). Treatment with the same antibody
      in Fas-deficient MRL/lpr mice blocked lymphadenopathy and lupus-like autoimmune
      processes. Paradoxically, transgenic non-obese diabetic (NOD) mice overexpressing
      membrane-bound agonistic single-chain anti-4-1BB Fv in pancreatic beta cells
      developed more severe diabetes than their non-transgenic littermates, with
      earlier onset, faster diabetic processes, and higher mortality. Forty percent of
      transgenic mice developed diabetes by 4 weeks of age, compared with their control
      littermates, which first exhibited diabetes at 14 weeks. The frequency of
      diabetes in female transgenics reached 70% by 8 weeks of age. Most female
      transgenic mice died around 12 weeks. Consistent with this, transgenic mice
      developed earlier and more severe insulitis and showed stronger GAD-specific T
      cell responses, compared with age-matched control littermates. Our results
      indicate an adverse effect of transgenic anti-4-1BB scFv in NOD mice and suggest
      a potential risk of this anti-4-1BB-based immunotherapy for autoimmune diseases.

PMID- 14599850
TI  - Regulation of immune and autoimmune responses by ICOS.
AB  - Proper T cell activation and function are regulated by the innate immune system,
      importantly through positive and negative costimulatory molecules in the B7
      superfamily. Inducible costimulator (ICOS), the receptor for B7h (also known as
      B7RP-1), is expressed on T cells after T cell activation. Recently, using ICOS
      deficient mice, we have examined the roles of ICOS in immune responses. ICOS is
      required for humoral immunity. In organ-specific autoimmune responses, however,
      ICOS has contrast roles in different disease models. On the one hand, ICOS-/-
      mice exhibited extreme sensitivity to experimental autoimmune encephalomyelitis
      (EAE); on the other, ICOS gene deletion led to complete resistance to collagen
      induced arthritis (CIA) in mice. Our work not only illustrates the complexity of
      immune regulation by costimulatory molecules, but also suggests novel therapeutic
      strategies for various autoimmune diseases.

PMID- 14599851
TI  - Role of ICAM-1 and P-selectin expression in the development and effector function
      of CD4+CD25+regulatory T cells.
AB  - Dynamic regulatory mechanisms prevent autoreactive T cell activation. Upon T cell
      receptor crosslinking, CD4+CD25+ T regulatory (T(R)) cells block both the
      proliferation and cytokine production of CD4+CD25- effector cells in an apparent
      antigen non-specific manner. Within the T(R)population, L-selectin
      (CD62L)(hi)T(R)cells have been described as more efficient suppressors of T cell
      proliferation than CD62L(low)T(R)cells. We have previously reported that
      CD4+CD25+CD62L(hi)T(R)cells express elevated levels of two additional adhesion
      molecules, ICAM-1 (CD54) and P-selectin (CD62P) in comparison to non-T(R)cells.
      In the current study, we investigated the functional contribution of CD54 and
      CD62P expression to the suppressive phenotype of T(R)cells both in vitro and in
      vivo. While the CD4+CD25+ T(R)cell population was demonstrated to be
      significantly larger in CD62P-/- mice than in wild-type C57BL/6 mice, CD62P-/-
      T(R)cell function was deficient in vitro, but not in vivo. Interestingly, we
      detected no deficiencies in T(R)cell numbers or effector function in CD54-/- mice
      suggesting that T(R)cells may differ from effector CD4+ T cells in the
      requirement for CD54 expression within the immunological synapse. Collectively,
      these findings indicate that CD62P may influence T(R)cell
      differentiation/development and that T(R)cell activation occurs independently of
      CD54 expression.

PMID- 14599852
TI  - Quantification of regulatory T cells in patients with systemic lupus
      erythematosus.
AB  - CD4+ T cells that constitutively express CD25 exhibit powerful suppressive
      properties. Such cells have been denominated regulatory T cells (T(R)).
      Alterations in T(R)cells are known to cause organ-specific autoimmune disease in
      animal models. The aim of this work was to quantify CD4+CD25+ T cells in patients
      with systemic lupus erythematosus (SLE). Thirty untreated patients (ten with
      active disease) and ten healthy volunteers were studied. Flow cytometry was used
      to quantify cell populations. CD4+CD69+, CD4+CD25+ and CD4+CD25(bright) cells
      were considered. Peripheral blood mononuclear cell cultures were performed and
      supernatants collected for IL-10 and 12 measurement. CD4+CD25+ cells were
      significantly decreased in patients with active disease when compared to control
      subjects and patients without disease activity (P<0.001). CD4+CD69+ cells were
      increased in patients with active disease when compared to controls (P=0.041).
      Accordingly, CD4+CD25(bright) cells were decreased in patients with active
      disease compared to healthy subjects (P<0.001). IL-12 production was hampered in
      cells from patients during periods of active disease when compared to healthy
      controls and patients during remission (P<0.001). We observed a correlation
      between decreased T(R)number and reduced IL-12 mononuclear cell production
      (r=0.362, P=0.05). This work demonstrates that CD4+CD25+ T cells are decreased in
      patients with clinically active SLE.

PMID- 14599853
TI  - Impaired responses to toll-like receptor 4 and toll-like receptor 3 ligands in
      human cord blood.
AB  - Toll-like receptor (TLR)-4 signaling pathway plays an essential role in host
      defense against gram-negative bacteria while TLR-3-mediated signaling is
      critically involved in anti-viral immunity. To gain insight into the defects
      responsible for impaired Th1 responses in human newborns, we investigated the
      responses of human cord blood cells to lipopolysaccharide, LPS, and to
      polyinosinic-polycytidylic acid, Poly (I:C), ligands of TLR-4 and TLR-3,
      respectively. Measurement of cytokine levels revealed a profound defect in IL-12
      (p70) synthesis and an increased release of IL-10 in cord blood exposed to LPS or
      Poly (I:C), as compared to adult blood. Moreover, Poly (I:C)-induced IFN-alpha
      production was found to be significantly impaired in cord blood. Phenotypic
      maturation of myeloid DC in response to LPS or Poly (I:C) was next compared in
      cord and adult blood. We observed that neonatal myeloid DC displayed decreased
      upregulation of CD40, CD80 whereas CD86 and HLA-DR upregulation did not differ
      significantly between adults and neonates. Taken together, these findings might
      be relevant to the increased vulnerability of human newborns to intracellular
      pathogens and to their inability to develop efficient Th1-type responses.

PMID- 14599855
TI  - Frozen cones: they have a niche.

PMID- 14599854
TI  - Humanized anti-interleukin-2 (IL-2) receptor alpha therapy: long-term results in
      uveitis patients and preliminary safety and activity data for establishing
      parameters for subcutaneous administration.
AB  - Therapy for severe uveitis is frequently long-term immunosuppression using
      systemic corticosteroids and cytotoxic agents, but side effects make long-term
      therapy difficult. A long-term (>4 year) Phase I/II single armed interventional
      study using intravenous anti-IL-2 receptor alpha treatments (daclizumab) and a
      short-term Phase II study evaluating the use of a subcutaneous daclizumab
      formulation were conducted. Patients were tapered off their systemic
      immunosuppressive therapy and received daclizumab infusions or subcutaneous
      injections at intervals varying from 2 to 6 weeks. In the long-term study, seven
      of ten enrolled patients were tapered from their original immunosuppressive
      medications and maintained exclusively on repeated daclizumab infusions for
      control of their uveitis for over 4 years. No patient was permanently removed
      from therapy for an adverse event ascribed to the medication. The use of 6-week
      infusion intervals led to recurrence of uveitis, while 2- to 4-week intervals did
      not. Only one patient developed measurable anti-daclizumab antibodies but this
      disappeared when subcutaneous therapy was begun. In the short-term study, four of
      the five patients receiving the subcutaneous formulation met the study endpoints
      for success within the first 12 weeks. All five were successful by 26 weeks.
      These studies provide preliminary evidence that regularly administered long-term
      daclizumab therapy can be given in lieu of standard immunosuppression for years
      to treat severe uveitis and that subcutaneously administered daclizumab appeared
      to be a clinically viable treatment strategy. These studies suggest that anti-IL
      2 receptor blockade could be useful in the treatment of Th1-mediated autoimmune
      conditions.

PMID- 14599856
TI  - Frozen section evaluation of cervical cold knife cone specimens is accurate in
      the diagnosis of microinvasive squamous cell carcinoma.
AB  - OBJECTIVES: The purpose of this study was to determine the accuracy of frozen
      section evaluation of cervical cold knife cone (CKC) specimens in the diagnosis
      of microinvasive squamous cell carcinoma (SCC). METHODS: Using ICD-9 codes for
      invasive and microinvasive carcinoma of the cervix, a medical record from 1986 to
      1998 identified 110 potential study subjects. Society of Gynecologic Oncologists
      criteria including depth of invasion < or =3 mm and absence of lymph-vascular
      space involvement were utilized for the diagnosis of microinvasion. Twenty-seven
      patients met study criteria including a frozen section diagnosis of microinvasive
      SCC on a cervical CKC specimen at our institution. A pathologist, blinded to
      patient diagnosis, reevaluated the histologic findings, including grade, depth of
      invasion, and cell type. RESULTS: Median age of diagnosis was 41 years. Median
      follow up was 3.6 years. The median time for pathologic review was 28 min (range
      15-44 min). Independent retrospective pathologic review of the permanent sections
      confirmed the diagnosis of microinvasion in 100% (27/27) of patients. No patient
      experienced a cervical SCC recurrence. At 10 years, disease-specific survival is
      100%. CONCLUSIONS: Frozen section is reliable in the evaluation of CKC specimens
      with microinvasive SCC: this may afford a simplified surgical approach in certain
      cases. This accuracy should not be assumed to apply to adeno- or adenosquamous
      carcinoma of the cervix. At our institution which relies heavily on
      intraoperative pathologic evaluation, utilizing frozen section diagnosis as the
      basis for definitive surgical approach did not negatively impact disease-free
      survival.

PMID- 14599857
TI  - Problems in reporting doses and volumes during multiple high-dose-rate
      intracavitary brachytherapy for carcinoma cervix as per ICRU Report 38: a
      comparative study using flexible and rigid applicators.
AB  - OBJECTIVE: The objective was to evaluate the extent of geometric and positional
      variations of two different applicators during multiple high-dose-rate (HDR)
      intracavitary brachytherapy (ICBT) in carcinoma cervix and its implication on
      reporting as per International Commission on Radiation Units and Measurement
      (ICRU) Report 38. METHODS: Fifty patients, following teletherapy, were randomly
      allocated to two groups of 25 each. They received a dose of 6 Gy to point A
      during each of the three HDR ICBT applications by either a flexible Ralstron or a
      rigid geometry Rotterdam applicator. The various applicator components related to
      its geometry and their Cartesian coordinates were evaluated from orthogonal
      films. The doses to ICRU bladder, rectal, pelvic, lymphatic trapezoid points, and
      dimensions of 6-Gy ICRU height, width, thickness, and volume were estimated for
      each application. RESULTS: Significant variation was observed with the three HDR
      ICBT applications for each group, for all components and for both applicators,
      although it was relatively more with the flexible Ralstron applicator. The
      average shift in each of the coordinates of os, uterine tip, and ovoids was
      around 10 mm for both groups. These resulted in significant variations in all the
      ICRU Report 38 reporting parameters for three insertions in any given patient and
      across 25 patients of both groups. CONCLUSIONS: Multiple HDR ICBT applications
      led to significant variation in the applicator geometry and its positions in
      pelvis, irrespective of the applicator rigidity. This results in uncertainties in
      reporting as per ICRU Report 38 guidelines, and thus calls for its revision.

PMID- 14599858
TI  - A phase II trial of three sequential doublets for the treatment of advanced
      mullerian malignancies.
AB  - OBJECTIVES: In an effort to improve the results of primary chemotherapy for
      mullerian malignancies a novel chemotherapy program was piloted that delivered
      three sequential chemotherapy doublets. The primary endpoints were surgically
      defined response rates and evaluation of toxicity. METHODS: After primary
      cytoreductive surgery patients were treated with three sequential doublets
      including three initial cycles of carboplatin and paclitaxel (doublet 1) and then
      two cycles of cisplatin (day 1) and gemcitabine (days 1 and 8; doublet 2), and
      finally two cycles of doxorubicin (day 1) and topotecan (days 3,4, and 5; doublet
      3). Cycles 4 through 7 were given with G-CSF (Neupogen) support at a dose of 5
      mcg/kg/day. After therapy, all women were clinically staged and evaluated by
      second-look laparoscopy/laparotomy (SLO) if clinical staging was negative for
      residual disease. RESULTS: A total of 49 eligible patients were enrolled with a
      median age of 52 (SD 9). Forty-four women had either ovarian cancer or primary
      peritoneal carcinoma with 3 women diagnosed with fallopian tube carcinoma and 2
      with papillary serous carcinoma of the uterus. Eighty-four percent of patients
      had stage IIIc/IV tumors, with 29% having >1 cm residual disease after primary
      cytoreductive surgery. Thirty-nine of 49 (80%) patients completed therapy. A
      total of 283 cycles of chemotherapy were delivered with acceptable toxicities.
      There were no toxic deaths. Five women were withdrawn from trial (3 for Taxol
      hypersensitivity, 1 for gemcitabine pulmonary hypersensitivity, and 1 for serious
      line infection). Neutropenia, typically without fever, was relatively frequent in
      the first doublet. Nausea and thrombocytopenia were the predominant toxicities in
      doublet 2. Thirty-nine women completed all cycles of treatment. Thirty-six women
      had restaging results consistent with a clinical complete response (CR) and
      underwent SLO. The pathologic CR rate of the patients undergoing SLO was 38%.
      CONCLUSIONS: Treatment with this sequential doublet regimen is feasible with a
      38% pathologic CR rate.

PMID- 14599860
TI  - Fas-mediated pathway and apoptosis in normal, hyperplastic, and neoplastic
      endometrium.
AB  - OBJECTIVES: Abnormalities in the control of cell proliferation and apoptosis have
      been suggested to contribute to the development and progression of neoplasia.
      There are at least two pathways that activate apoptosis. The first is a
      mitochondria-dependent route governed by bcl-2 family proteins. The second is a
      parallel mechanism which involves the activation of a group of tumor necrosis
      factor (TNF) receptors, such as Fas. METHODS: The aim of this study was to
      examine the distribution and interrelation between the expression patterns of
      apoptosis-related proteins such as Fas, caspase-3 (CPP32), and M30, and to
      investigate the role of Fas-mediated apoptosis in the pathogenesis and
      progression of endometrial neoplasms. RESULTS: Using specific antibodies for Fas,
      caspase-3, and M30, we examined protein expressions in 29 endometrial carcinomas,
      30 endometrial hyperplasias, and 21 normal cyclic endometria. The results of
      immunostaining for Fas and caspase-3 were analyzed semiquantitatively by using an
      immunohistochemical scoring system (HSCORE) that incorporated both the intensity
      and the distribution of specific staining. For M30, positive staining cells and
      extracellular particles were analyzed semiquantitatively per 10 high-power
      fields.HSCOREs of Fas and caspase-3 were slightly higher in the secretory
      endometria than in the proliferative endometria. Similarly, M30 reactivity seemed
      to increase in the late secretory phase of the cycle. HSCOREs of Fas and caspase
      3 and the reactivity of M30 were significantly higher in the carcinoma group than
      in the simple hyperplasia group (P < 0.05). Complex hyperplasias, however,
      expressed quite similar HSCOREs of Fas and caspase-3 as carcinomas. M30
      reactivity was also significantly higher in complex hyperplasias than in simple
      hyperplasias, and in carcinomas positivity increased significantly (P < 0.05) as
      the grade progressed. CONCLUSIONS: The significant increase observed in Fas,
      caspase-3, and M30 expression in carcinomas as compared with simple hyperplasias
      may suggest that the Fas-related apoptotic pathway is also involved in the
      regulation of apoptosis in the endometrial tissue and promotes the development
      and progression of endometrial neoplasia.

PMID- 14599859
TI  - 2-methoxyestradiol strongly inhibits human uterine sarcomatous cell growth.
AB  - OBJECTIVES: The objective was to test the hypothesis that uterine sarcomatous
      cells are hormone-sensitive. We included 2-methoxyestradiol, an endogenous
      metabolite of estradiol with antiproliferative properties. METHODS: Proliferation
      assays assessed the effects of estradiol, progesterone, tamoxifen, raloxifen, [D
      Trp(6)]leuteinizing hormone-releasing hormone (LHRH), ICI 182,780 (faslodex or
      fulvestrant), and 2-methoxyestradiol on cell growth of a cell line derived from
      uterine carcinosarcoma, but consisting solely of mesenchymal cells (SK-UT-1).
      Morphological changes of SK-UT-1 cells after exposure to 2-methoxyestradiol were
      evaluated and fluorescence immunohistochemistry for tubulin was used to detect
      changes in the mitotic spindle. Flow cytometry was used to assess the influence
      of 2-methoxyestradiol on the SK-UT-1 cell cycle as well as the role of p53 in
      apoptosis. RESULTS: Cell proliferation analysis revealed that SK-UT-1 cells were
      stimulated by progesterone, tamoxifen, and [D-Trp(6)]LHRH. Cells were insensitive
      to estradiol, raloxifen, and ICI 182,780. Inhibition occurred after exposure to 2
      methoxyestradiol and was accompanied by a threefold increase in the G2/M
      population, with a concomitant decrease in the G1 population, as shown by cell
      cycle analysis. SK-UT-1 cells exposed to 2-methoxyestradiol showed morphological
      changes indicative of apoptosis. Examination of signaling pathways that mediate 2
      methoxyestradiol-induced apoptosis showed p53-independent growth inhibition. The
      inhibition of SK-UT-1 cell growth by arresting the cells during G2/M progression
      could be attributed to interference with the microtubule system, as determined by
      fluorescence immunohistochemistry. CONCLUSIONS: The stimulatory effect of
      progesterone, tamoxifen, and [D-Trp(6)]LHRH suggests that uterine sarcomatous
      cells are hormone-sensitive. Our finding that 2-methoxyestradiol-mediated growth
      inhibition of uterine sarcomatous cells occurred in a p53-independent manner may
      have considerable clinical significance. The inadequate armature against uterine
      sarcomas and the limited toxicity of 2-methoxyestradiol may render these
      observations especially important.

PMID- 14599861
TI  - A phase II study to determine the efficacy and tolerability of intravenous ZD9331
      in heavily pretreated patients with ovarian cancer.
AB  - OBJECTIVES: This Phase II, multicenter, open-label study was conducted to assess
      the efficacy and tolerability of ZD9331, a novel direct-acting thymidylate
      synthase inhibitor, in heavily pretreated patients with ovarian cancer. METHODS:
      The study recruited 44 women with ovarian cancer or primary peritoneal cancer
      previously treated with platinum therapy and paclitaxel and with progressive
      disease after, or intolerance to, topotecan administered as the most recent
      therapy. ZD9331 was administered as an intravenous infusion at 130 mg/m(2) on
      Days 1 and 8 of 3-week cycles, until objective evidence of disease progression. A
      cutoff date of 3 months after the last patient received the first dose was set
      for data collection. RESULTS: Patients received a mean of 3.3 cycles of ZD9331
      and a total of 143 cycles were administered. Among the 42 patients evaluated for
      best overall tumor response, one achieved a complete response and two achieved a
      partial response, giving an objective tumor response rate of 7%. The complete
      response occurred at Day 15 of Cycle 2 in a patient receiving ZD9331 as her
      eighth-line therapy. Seven patients had stable disease, giving a disease control
      rate of 23%. Thirty-one patients (71%) had disease progression and the median
      time to progression was 53 days. Most patients (89%) experienced drug-related
      adverse events, most commonly nausea (73%), vomiting (48%), and neutropenia
      (50%). Six patients (14%) were withdrawn from treatment due to adverse events.
      CONCLUSIONS: The preliminary evidence of efficacy and acceptable tolerability of
      ZD9331 in this heavily pretreated population with ovarian cancer warrants further
      investigation, especially in a less heavily pretreated patient population.

PMID- 14599862
TI  - Prospective evaluation of surgical staging of advanced cervical cancer via a
      laparoscopic extraperitoneal approach.
AB  - OBJECTIVES: To report on a large series of cervical cancer patients at risk for
      lymph node metastasis who underwent surgical staging by a novel technique.
      METHODS: Between 1/97 and 3/02, we identified 111 patients who underwent an
      infrarenal aortic and common iliac lymph node dissection via a laparoscopic
      extraperitoneal approach for either bulky or locally advanced cervical cancer. We
      reviewed the medical records and extracted pertinent information. RESULTS: There
      were no intraoperative complications. Mean patient age was 46 (+/- 9) years. Mean
      node count was 19 (+/- 12). Thirty (27%) patients had lymph node metastasis. The
      mean operative time was 157 (+/- 46) min, and mean postoperative stay was 2 days.
      The majority of complications in the early part of the series were symptomatic
      lymphoceles. Since 4/01, preventive peritoneal marsupialization has been
      performed without lymphocele occurrence (37 patients). Two patients (2%) required
      reoperation. In the node-positive group, extended-field radiation and
      chemotherapy were well tolerated, but prognosis was dismal (median survival, 27
      months). In the node-negative group, the median survival after pelvic radiation
      limited to the lower level of the surgical dissection was not reached after an
      average follow-up of 16.6 months. CONCLUSIONS: This novel technique is feasible
      and combines the benefits of laparoscopy with those of a retroperitoneal
      approach. It can be used to tailor external radiation therapy. The benefits of
      extended-field radiation therapy remain unclear; however, this approach does not
      preclude later use of radiation therapy, whereas possibly minimizing associated
      toxicities secondary to adhesions.

PMID- 14599863
TI  - Aqueous extract of herba Scutellaria barbatae, a chinese herb used for ovarian
      cancer, induces apoptosis of ovarian cancer cell lines.
AB  - OBJECTIVES: Given the increasingly common use of complementary medicine in cancer
      patients, we tested the in vitro cytotoxicity of aqueous extracts of 15
      traditional Chinese herbs with purported anticancer properties on ovarian and
      breast cancer cell lines. METHODS: Cell viability after treatment with herbal
      extract was measured by metabolism of a tetrazolium substrate. Apoptosis was
      measured by nuclear and DNA fragmentation and Annexin V binding. RESULTS: One
      herb, Herba Scutellaria barbatae, was cytotoxic to 100% (11 of 11) of actively
      proliferating ovarian lines tested and 50% (2 of 4) of actively proliferating
      breast cell lines tested. Confluent cultures were resistant to killing by herb,
      whereas subconfluent cultures were sensitive. Resistant proliferating cell lines
      expressed higher levels of bcl2. Transfection of the most sensitive ovarian
      cancer cell line (A2780) with bcl2 resulted in a noticeable protection against
      apoptosis, but there was no protection in other transfected lines. CONCLUSIONS:
      These results will be useful in guiding future studies of herbal aqueous
      extracts, as well as providing information for clinicians when patients are
      concurrently using these herbs along with conventional cancer therapies.

PMID- 14599864
TI  - Long-term survival with consolidation intraperitoneal chemotherapy for patients
      with advanced ovarian cancer with pathological complete remission.
AB  - OBJECTIVES: The goal of this study was to evaluate the long-term outcome after
      consolidation intraperitoneal (IP) chemotherapy in patients with a negative
      second-look laparotomy (SLL) following first-line intravenous chemotherapy for
      advanced ovarian cancer. METHODS: This study included patients with FIGO stage
      III-IV ovarian cancer who entered into four prospective trials (1984-1995)
      including intravenous chemotherapy based on cisplatin (six cycles) and
      anthracycline, early debulking surgery after three cycles of chemotherapy in the
      case of initial residual disease >2 cm, SLL, and IP consolidation chemotherapy.
      Among 218 patients, 68 with biopsy-negative SLL received every 4 weeks three
      consolidation cycles of IP chemotherapy (mitoxantrone, cisplatin, etoposide) via
      a totally implantable port. Long-term outcome of these patients is reported.
      RESULTS: Mean age was 56 years (33-72 years). Overall, 51% of the patients had at
      least a grade 3 or 4 toxic effect. Main toxic effects were leukopenia, abdominal
      pain related to the catheter, and nausea and vomiting. Only 13 patients (19%) did
      not receive the full three cycles. The median progression-free survival (PFS) for
      the whole population is 34 months, 34% of the patients being estimated to be free
      of disease at 5 years. The median overall survival is 73 months, and the 5-year
      survival is 58%. CONCLUSIONS: In this selected population treated with IP
      consolidation chemotherapy, prolonged survival was observed. However, the
      occurrence of late relapses in this most favorable patient category underlines
      the need to improve the consolidation therapy options in ovarian cancer.

PMID- 14599865
TI  - P63 and EGFR as prognostic predictors in stage IIB radiation-treated cervical
      squamous cell carcinoma.
AB  - OBJECTIVES: The purpose of this study was to determine the relation between p63,
      p53-related gene, epidermal growth factor receptor (EGFR), and spontaneous
      apoptosis in relation to radiotherapy in patients with FIGO stage IIB cervical
      carcinoma, who had undergone radiation and concurrent chemotherapy,
      retrospectively. METHODS: Eighty-four patients with FIGO stage IIB squamous cell
      carcinoma (SCC) of the uterine cervix, who were treated with radiotherapy and
      concurrent chemotherapy between 1991 and 1996, were included in the present
      study. The clinicopathologic features, patterns of treatment failure, and
      survival data were compared with the expressions of p63 and EGFR, which were
      determined by immunohistochemistry and with apoptosis by TUNEL on tissue-arrayed
      slides. Univariate and multivariate analyses were performed to determine the
      prognostic factors that influence patient survival. RESULTS: Overall the indices
      of the expressions of p63 and EGFR in stage IIB cervical carcinoma were 18.7 and
      26.6%, respectively, and these were found to be correlated. EGFR expression was
      significantly associated with extrapelvic failure (P = 0.03), whereas p63 was
      associated with locoregional failure (P = 0.03). The spontaneous apoptotic index
      showed no prognostic value, but the immunoreactivities of p63 and EGFR were
      associated with a worse prognosis by both univariate (P = 0.01 and 0.04,
      respectively) and multivariate analysis (95% CI:2.0-4.4, RR:3.2 and 95% CI:4.9
      8.7, RR:6.7, respectively). CONCLUSIONS: The expression of p63 gene is associated
      with poor survival and locoregional failure, whereas EGFR expression was found to
      be a prognostic predictor of extrapelvic failure. Both molecules were found to be
      potent molecular risk factors in patients with FIGO stage IIB SCC of the uterine
      cervix, who had received radiotherapy and concurrent chemotherapy.

PMID- 14599866
TI  - Interferon regulatory factor-1 expression in human uterine endometrial carcinoma.
AB  - OBJECTIVES: The objective was to investigate the expression of interferon
      regulatory factors 1 (IRF-1) in human uterine endometrial carcinoma. METHODS:
      Formalin-fixed, paraffin-embedded, archival tissue specimens from 76 human
      endometrial carcinomas and stained with polyclonal anti-IRF-1 antibody, using
      immunohistochemistry, localization, and immunostaining, were evaluated
      quantitatively using the H score together with 30 normal endometrium and 16
      postmenopausal endometrium. RESULTS: The expression of IRF-1 was highest in
      normal endometrium, and decreased with the grade of endometrioid adenocarcinoma
      from grade 1 to grade 3. Postmenopausal endometrium was virtually unstained.
      CONCLUSIONS: Expression of IRF-1 is altered in human endometrioid adenocarcinoma
      compared with normal endometrium and postmenopausal endometrium. The loss of IRF
      1 expression does not contradict with the tumor-suppressor function. The
      intensity of IRF-1 expression in each grade of endometrioid adenocarcinoma could
      be useful prognostic and therapeutic indicators.

PMID- 14599867
TI  - "Schauta sine utero": technique and results of laparoscopic-vaginal radical
      parametrectomy.
AB  - OBJECTIVES: Radical parametrectomy or radical cervical stump exstirpation is
      indicated in selected oncologic situations. We evaluated whether radical
      parametrectomy without or with cervical stump exstirpation can be performed by a
      combined laparoscopic-vaginal approach. METHODS: Between November 2001 and
      Dezember 2002 six patients with unexpected cervical cancer (n = 3) after simple
      hysterectomy, histologically confirmed vaginal recurrence of endometrial cancer
      (n = 1), or cervical stump recurrence of endometrial cancer after supracervical
      hysterectomy (n = 2) underwent radical parametrectomy. After cystoscopic
      placement of bilateral ureteral stents laparoscopic paraaortic and pelvic
      lymphadenectomy was performed. The vascular part of the cardinal ligament and the
      bladder pillar were transsected laparoscopically. According to a LARVH type III
      procedure vaginal vault or cervical stump with parametrial and paravaginal
      structures was removed transvaginally. RESULTS: In all patients R0 resection
      could be achieved (n = 4) or no residual tumor was detected (n = 2). There were
      no intraoperative complications. One patient developed acute kidney failure on
      postoperative day 1, with spontaneous recovery after 12 days. The median drop of
      hemoglobin on postoperative day 5 was 2.15 mmol/L (1.3-3.2) and no patient needed
      transfusion. Restitution of bladder function took 4.3 days on average. The mean
      operation time was 424 min (385-452). CONCLUSIONS: Radical parametrectomy can be
      performed by a combined laparoscopic-vaginal technique without complications.
      Together with laparoscopic paraaortic and pelvic lymphadenectomy, it is a valid
      alternative to open surgery in selected oncologic patients.

PMID- 14599868
TI  - Laterally extended endopelvic resection. Novel surgical treatment of locally
      recurrent cervical carcinoma involving the pelvic side wall.
AB  - OBJECTIVES: To demonstrate the therapeutic potential of the laterally extended
      endopelvic resection (LEER) especially for patients with recurrent cervical
      carcinomas involving the side wall of an irradiated pelvis. These patients,
      suffering from the most common situation of local failure, have so far no longer
      been considered for curative therapy. METHODS: Extending the lateral resection
      plane of pelvic exenteration to the medial aspects of the lumbosacral plexus,
      sacrospinous ligament, acetabulum, and obturator membrane enables the complete
      removal of a subset of locally advanced and recurrent tumors of the lower female
      genital tract fixed to the pelvic wall with free margins (R0). Patients selected
      for LEER were accrued to a prospective outcome trial. RESULTS: Thirty-six
      patients with recurrent (n = 29) or primary advanced (n = 7) gynecologic
      malignancies involving the side wall of the lesser pelvis underwent LEER from
      July 1996 until October 2002. The majority of the patients suffered from cervical
      carcinoma (n = 29) and had received previous pelvic irradiation (n = 24). Tumor
      free (R0) lateral margins were obtained in 34 patients. Severe postoperative
      complications occurred in 14 patients with one treatment-related death. Five-year
      survival probability is 49% for the whole group and 46% for those patients
      considered only for palliation with current treatment options. Most patients
      without evidence of disease at least 1 year after LEER achieved good quality of
      life. CONCLUSIONS: LEER can be offered as novel surgical salvage therapy to a
      selected subset of patients with locally advanced and recurrent cervical
      carcinoma involving the pelvic wall.

PMID- 14599869
TI  - Pathologic evaluation of inguinal sentinel lymph nodes in vulvar cancer patients:
      a comparison of immunohistochemical staining versus ultrastaging with hematoxylin
      and eosin staining.
AB  - OBJECTIVES: To evaluate the value of immunohistochemical (IHC) staining of
      inguinal sentinel lymph nodes (SLN) found to be negative for metastatic disease
      by ultrastaging with hematoxylin and eosin (H&E) staining. METHODS: An IRB
      approved study identified 29 patients who had undergone an inguinal sentinel
      lymph node dissection for squamous cell carcinoma of the vulva. All sentinel
      lymph nodes found to be negative for metastatic disease based on ultrastaging
      with H&E staining were reevaluated with pancytokeratin antibody (AE1/AE3)
      immunohistochemical (IHC) staining to detect micrometastasis. RESULTS: Twenty
      nine patients with squamous cell carcinoma of the vulva underwent an inguinal
      sentinel node dissection. Nineteen patients had inguinal dissections negative for
      metastatic disease, 2 patients had bilateral inguinal metastasis, and 8 patients
      had unilateral inguinal metastasis. A total of 42 groin dissections with SLN
      biopsies were performed; 12 groins were positive for metastatic disease and 30
      were negative based on ultrastaging with eosin and hematoxylin staining. A total
      of 107 sentinel lymph nodes (2.5 SLN per groin) were obtained, of which 18 SLN
      contained metastatic disease identified by ultrastaging and staining with H&E.
      Two SLN contained micrometastasis less than 0.3mm in size and 16 SLN contained
      metastasis greater than 2mm in size. Eighty-nine SLN found to be negative for
      metastasis by ultrastaging with H&E staining were also negative for
      micrometastasis on evaluation with pancytokeratin antibody AE1/AE3 IHC staining.
      CONCLUSIONS: The addition of immunohistochemical staining to ultrastaging with
      H&E staining in the pathologic evaluation of inguinal sentinel lymph nodes does
      not increase the detection of micrometastasis in patients with primary squamous
      cell carcinoma of the vulva.

PMID- 14599870
TI  - Resection of recurrent ovarian or fallopian tube carcinoma involving the liver.
AB  - OBJECTIVES: Patients who develop recurrent ovarian of fallopian tube carcinoma
      involving the liver often have disease refractory to chemotherapy and carry a
      poor prognosis. The impact of aggressive resection in this patient population is
      unclear. METHODS: From 1/1988 to 9/2001, 24 patients with recurrent ovarian or
      fallopian tube carcinoma who underwent complete gross resection or optimal
      debulking of their hepatic metastases and disease at other sites were identified
      from prospective databases at a single institution. RESULTS: The median age of
      patients was 53 years old, and the median interval between primary diagnosis and
      liver resection was 69 months. All patients had primary resection or
      cytoreduction and chemotherapy as part of their initial treatment. Subsequent
      hepatic resections included trisegmentectomy (2), lobectomy (2), segmentectomy
      (17), and wedge resection (3). Additional resection of disease outside the liver
      was performed in 18 patients (75%). Twenty-one patients (88%) had removal of all
      gross disease, and three patients (13%) had optimal tumor debulking to less than
      1 cm. Eighteen patients recurred with sites of initial recurrence, including the
      abdomen and pelvis (14), spine/paraspinal region (2), lung (1), and liver (1).
      Overall median survival was 62 months after hepatic resection with a range of 6
      to 94 months. Fourteen patients were alive at the time of last follow-up, and 10
      had no evidence of disease. No significant prognostic factors for overall
      survival could be identified on univariate analysis. CONCLUSIONS: In highly
      selected patients with recurrent ovarian or fallopian tube carcinoma involving
      the liver, hepatic resection along with resection of other gross disease may
      lengthen survival and should be considered as a treatment option.

PMID- 14599871
TI  - Preoperative detection of peripherally circulating cancer cells and its
      prognostic significance in ovarian cancer.
AB  - OBJECTIVES: Studies in several solid tumors have shown that the presence of
      occult metastasis in the bone marrow or peripheral blood is highly predictive of
      decreased disease-free and overall survival. Our objective was to determine the
      incidence of circulating ovarian or primary peritoneal cancer cells in the
      peripheral blood at the time of disease diagnosis, or recurrence, and to
      determine the prognostic significance of these occult metastasis. METHODS:
      Peripheral blood was drawn preoperatively from 91 women thought to have newly
      diagnosed or recurrent epithelial ovarian or primary peritoneal carcinoma. All
      samples underwent a tumor-enriched immunocytochemical assay. RESULTS: Sixty-four
      women were found to have epithelial ovarian or primary peritoneal cancer. Of the
      64 women with cancer, 12 had evidence of circulating cancer cells in their
      peripheral blood (18.7%). Characteristics were compared between those with
      circulating cancer cells and those without, using Fisher's exact test or the
      Wilcoxon-Mann-Whitney test, as appropriate. Women with circulating cancer cells
      had statistically more grade 3 tumors than women without. At a mean follow-up of
      18.7 months (SD 6.7 months), analysis using Kaplan-Meier estimation and the log
      rank test indicated that survival curves did not differ between patients with and
      without circulating cancer cells. CONCLUSIONS: Ovarian and primary peritoneal
      cancer, which historically has been thought to spread primarily by direct cell
      seeding throughout the abdominal cavity, can have circulating cancer cells in the
      peripheral blood. The clinical utility of identifying circulating cancer cells is
      yet to be defined.

PMID- 14599872
TI  - Survival and prognosis of women with invasive cervical cancer according to age.
AB  - OBJECTIVES: We assessed survival and compared clinical and pathological
      prognostic factors of women with invasive cervical cancer according to the age in
      order to define a cutoff point where screening should become useless. METHODS:
      The survival of 308 women with invasive cervical cancer treated at Bordeaux
      University Hospital between 1976 and 1996 was evaluated on December 31, 2000.
      Kaplan-Meier survival curves calculated with regard to age were compared by the
      log-rank test. Prognostic factors were assessed according to age (cutoff 65
      years) and included in a Cox model. Survival of women in our population within a
      particular age group was compared to survival of women of the same age range,
      using indirect standardization. RESULTS: The 5-year survival rate of women under
      65 (n = 221), between 65 and 74 (n = 56), and over 75 (n = 31) was 75%, 69%, 42%,
      respectively (P < 0.001). Compared to women under 65, women over 65 had a
      significantly lower Karnofsky performance status and a significantly more
      advanced clinical stage cancer involving vaginal bleeding. Age, gross cervical
      appearance, clinical vaginal involvement, histologic grade, and microscopic
      cervical and parametrial involvements were independent prognostic factors.
      Compared to women under 65, the risk of mortality was 1.3, 95% CI = 0.8-2.7, P =
      0.189, for women aged 65-74, and 2.3, 95% CI = 1.1-3.9, P = 0.022, for women over
      75. Mortality of women with invasive cervical cancer was significantly higher
      than that of women in the general population in the indirect standardization
      model (SMR = 1.9, 95% CI = 1.5-2.2), except beyond age 75. CONCLUSIONS: Age was a
      significant prognostic factor in our study and advanced stages were significantly
      increased after 65. However, survival after 75 was not different from that of the
      population. These considerations address the question of the maintenance of
      screening between 65 and 75.

PMID- 14599873
TI  - Total laparoscopic radical hysterectomy with pelvic lymphadenectomy using the
      argon-beam coagulator: pilot data and comparison to laparotomy.
AB  - OBJECTIVES: The aim of this study was to describe the feasibility and outcome of
      total laparoscopic radical hysterectomy with pelvic lymphadenectomy for stage I
      cervical cancer using the argon-beam coagulator. METHODS: A retrospective review
      was performed of patients with FIGO stage IA1-IB1 cervical cancer who underwent a
      total laparoscopic approach for definitive surgical treatment. Comparison was
      made to a cohort of 195 patients who were treated with laparotomy. RESULTS:
      Between 12/2000 and 12/2002, 19 patients were offered the laparoscopic approach.
      The procedure was completed laparoscopically in 17 patients (89.5%). Two
      patients, in the beginning of the study, underwent conversion to laparotomy, 1
      due to parametrial bleeding and 1 due to pelvic adhesions and cystotomy. Mean age
      was 42.6 years (range, 30-69 years); mean body mass index was 23.1 (range, 18
      30); FIGO stage included IA1 with LVI (2), IA2 (6), IB1 (11). Mean pelvic lymph
      node count was 25.5 (range, 15-39), and 1 patient (5.3%) had positive nodes. Mean
      estimated blood loss was 301 cc (range, 75-1500 cc) compared to 693 cc in the
      laparotomy group (P < 0.01), mean operating time was 371 min (range, 230-600 min)
      compared to 295 min in the laparotomy group (P < 0.01), and mean hospital stay
      was 4.5 days (range, 3-11 days) compared to 9.7 days in the laparotomy group (P <
      0.01). There were no ureteral injuries or fistula formation. All patients remain
      clinically disease free at the time of this report. CONCLUSIONS: Total
      laparoscopic radical hysterectomy with pelvic lymphadenectomy for selected
      patients with stage I cervical cancer is feasible, safe, and associated with a
      low morbidity in the pilot phase. Estimated blood loss and postoperative
      hospitalization appear shorter than historical controls, at the cost of longer
      operating time. Oncologic outcome requires longer follow-up.

PMID- 14599874
TI  - In vitro downregulation of growth factors by insulin-like growth factor binding
      protein-3 in cervical cancer.
AB  - OBJECTIVES: Our hypothesis is that insulin-like growth factor binding protein 3
      (IGF-BP3) would downregulate epidermal growth factor receptor (EGF-R) levels in
      cervical cancer cell lines, thereby reducing cellular IGF-II and angiogenesis
      related vascular endothelial cell growth factor (VEGF). As folate deficiency is a
      risk factor in cervical cancer, we sought to determine if folic acid treatment
      might increase IGF-BP3 production, thereby inhibiting malignant cell
      proliferation. METHODS: We determined the cellular levels of EGF-R, IGF-II, and
      VEGF in the cervical cancer cell lines HeLa, ME-180 (both positive for human
      papilloma virus; HPV), and HT-3 (HPV-negative), following their treatment with
      IGF-BP3. Levels of IGF-BP3 in these cells before and after treatment with folic
      acid and VEGF were also enumerated, using a computerized semiquantitative
      immunofluorescent antibody assay. RESULTS: Treatment with IGF-BP3 significantly
      reduced the levels (mean intensity per pixel) of EGF-R, IGF-II, and VEGF in all
      three cell lines and IGF-I receptor (IGF-IR) in representative ME-180 cell line.
      Treatment with antiproliferative folic acid increased IGF-BP3 levels while the
      proliferative VEGF depleted cellular IGF-BP3 in all the cell lines. CONCLUSIONS:
      Levels of EGF-R, IGF-II, IGF-IR, and VEGF are significantly reduced following
      treatment with IGF-BP3 in cervical cancer. We observed increased levels of IGF
      BP3 by folic acid, and decreased IGF-BP3 levels by VEGF. Downregulation of EGF-R
      by IGF-BP3 suggests an IGF-independent action. Folate deficiency is a risk factor
      in cervical cancer. Our results suggest that folic acid supplementation can lead
      to inhibition of cervical cancer cell growth by promoting increased IGF-BP3
      levels.

PMID- 14599875
TI  - Ligation of an anatomic variant of renal vasculature during laparoscopic
      periaortic lymph node dissection: a cause of postoperative renal infarction.
AB  - OBJECTIVES: Minimally invasive surgical techniques are becoming more
      sophisticated as complex procedures are being incorporated into gynecologic
      oncology in routine and investigative settings. CASE: We present a case of an
      aberrant supernumerary right renal artery ligation during periaortic laparoscopic
      lymph node dissection for endometrial cancer. This injury resulted in infarction
      of the lower pole of the right kidney, with no late sequela. CONCLUSIONS: The
      gynecologic oncologist should be aware of the possibility of aberrant renal
      vasculature, and special care should be taken to avoid accidental ligation of
      supernumerary renal arteries during dissection of the periaortic lymph nodes.

PMID- 14599876
TI  - Gemcitabine-induced radiation recall dermatitis following whole pelvic radiation
      therapy.
AB  - OBJECTIVES: Radiation recall dermatitis secondary to gemcitabine use has been
      reported in isolated cases of patients treated for breast and lung cancers. There
      have been no reports of radiation recall dermatitis from gemcitabine after whole
      pelvic radiation therapy employed as a treatment of a gynecologic cancer. CASE: A
      67-year-old woman was treated with whole pelvic radiation for palliation of lower
      extremity swelling and pain due to recurrent ovarian adenocarcinoma. Three months
      later, the patient was treated with gemcitabine for three courses. Therapy was
      discontinued secondary to severe cellulitis and edema of the skin of the anterior
      abdominal wall in the field of her prior radiation therapy. CONCLUSIONS:
      Radiation recall dermatitis secondary to gemcitabine should be considered in any
      patient with pelvic or lower abdominal skin abnormalities after pelvic radiation
      and subsequent gemcitabine therapy.

PMID- 14599877
TI  - Improvement of paclitaxel-induced neuropathy by substitution of docetaxel for
      paclitaxel.
AB  - OBJECTIVES: Although the combination of paclitaxel and carboplatin has a better
      therapeutic index than the combination of paclitaxel and cisplatin, peripheral
      neuropathy often occurs and remains the most chronic toxicity of this therapy.
      CASE: Six patients with ovarian or peritoneal carcinoma who developed grade 2
      peripheral neuropathy during chemotherapy with paclitaxel and carboplatin had
      decreased or resolution of their neuropathy after their therapy was changed to
      docetaxel and carboplatin. CONCLUSIONS: Changing the taxane from paclitaxel to
      docetaxel in combination with carboplatin resulted in decreased or resolution of
      established peripheral neurotoxicity. This is one strategy to allow continued
      taxane therapy in the face of progressing peripheral neuropathy.

PMID- 14599878
TI  - Malignant mixed mullerian tumor of the ovary and bilateral breast cancer: an
      argument for BRCA3, or a coincidental cluster of unconnected cancers?
AB  - OBJECTIVES: Malignant mixed mullerian tumors (MMMTs) of the ovary are a rare,
      aggressive subtype of ovarian cancer without a clear relationship to familial
      breast-ovarian cancer syndromes. CASE: We present the case of a woman with
      bilateral breast cancers who subsequently developed a stage IIIc MMMT of the
      ovary. The patient had a first-degree female relative with breast and ovarian
      cancer (not MMMT), as well as second- and third-degree female relatives each with
      bilateral breast cancers. BRCA1 and BRCA2 sequencing of germline DNA revealed no
      evidence of a heritable mutation. CONCLUSIONS: Ovarian MMMTs may be a hallmark of
      breast/ovarian cancer secondary to genetic risk independent of classic BRCA1/2
      pathways.

PMID- 14599879
TI  - Laparotomy wound recurrence of endometrial carcinoma.
AB  - OBJECTIVES: Most endometrial cancer relapses are either pelvic or distant
      metastases. Recurrences in the laparotomy scar are extremely rare, as to our
      knowledge this is only the sixth reported case and the first treated with
      brachytherapy. We also present a review of the literature with an emphasis on
      radiation therapy treatment. CASE: A 64-year-old woman underwent total abdominal
      hysterectomy and bilateral salpingo-oophorectomy for IIIA endometrial
      adenocarcinoma, followed by systemic chemotherapy and pelvic external-beam
      radiotherapy. Three years later, a recurrence in the laparotomy scar was resected
      and additional chemotherapy was administered. A solitary mass in the abdominal
      wound was then found 4 years after that and was reirradiated by combining
      external-beam radiation therapy and interstitial brachytherapy after complete
      resection. Histology of the abdominal wall implants was very similar to that of
      the primary tumour. CONCLUSIONS: Laparotomy wound recurrence (LWR) for
      endometrial cancer usually appears as a solitary mass that grows slowly without
      concomitant failure sites a few years after hysterectomy. In these six patients
      there is no common histology pattern that could suggest predictive factors for
      LWR. Common postoperative irradiation does not deliver sufficient a dose to the
      anterior abdominal wall to prevent this kind of failure.

PMID- 14599880
TI  - A case of prolonged carboplatin therapy in a patient with carboplatin
      hypersensitivity.
AB  - OBJECTIVES: Platinum-containing chemotherapeutic drugs have high response rates
      yet are known to cause hypersensitivity reactions. Attempts have been made to
      rechallenge allergic patients with prolonged desensitization infusion regimens.
      CASE: A female with advanced peritoneal cancer went into remission after six
      cycles of paclitaxel/cisplatin. Her cancer recurred 17 months later and she was
      treated with paclitaxel/carboplatin. A hypersensitivity reaction to carboplatin
      occurred during the fourth cycle and further carboplatin was withheld. With the
      second recurrence carboplatin was resumed using a prolonged desensitization
      regimen. The patient had a third recurrence and has recently completed cycle 15
      of carboplatin for a total of 56 cycles. CONCLUSIONS: A carboplatin
      desensitization regimen may allow patients with platinum-sensitive ovarian or
      peritoneal cancer to continue to benefit from its efficacy.

PMID- 14599881
TI  - Cystadenocarcinoma of the abdominal wall following caesarean section: case report
      and review of the literature.
AB  - OBJECTIVES: Endometriosis affecting surgical scars is a well-described entity
      that can complicate surgery involving hysterotomies. Malignant transformation is
      a rare event that has been reported complicating ovarian endometriosis mainly.
      CASE: A 60-year-old woman having in the past two uneventful caesarean deliveries
      presented with a solid lower abdominal mass. A surgical biopsy and then a radical
      resection of the lower half of the abdominal wall were performed, with a
      diagnosis of adenocarcinoma of endometrial origin. A diagnostic curettage
      excluded primary endometrial carcinoma. At 1 year she is NED. CONCLUSIONS: This
      case report illustrates the carcinomatous transformation of an endometrial
      implant. Despite the rarity of such a diagnosis, it should be borne in mind when
      endometriosis in abdominal wall is suspected because an oncological resection is
      required.

PMID- 14599882
TI  - Malignant mixed Mullerian tumor of the uterine corpus with alpha-fetoprotein
      producing hepatoid adenocarcinoma component.
AB  - OBJECTIVES: Hepatoid adenocarcinoma is a rare tumor and has the histological
      coexistence of well-differentiated adenocarcinoma and nests of hepatoid cells
      with immunoreactivity for alpha-fetoprotein (AFP). A case of hepatoid
      adenocarcinoma in malignant mixed Mullerian tumor of the uterus is presented with
      a review of the literature. CASE: The patient is a 63-year-old woman who
      complained of abnormal genital bleeding. Serum AFP concentration was 5060 ng/ml.
      Histologically, the tumor was composed of endometrioid adenocarcinoma, neoplastic
      hepatoid cells, and sarcoma component including leiomyosarcoma and
      rhabdomyosarcoma. After operation followed by six courses of platinum-based
      chemotherapy, serum levels of AFP dropped into normal range. CONCLUSIONS: This
      is, to our knowledge, the first report of malignant mixed Mullerian tumor of the
      uterus with an AFP-producing hepatoid adenocarcinoma component.

PMID- 14599883
TI  - 24-year-old female with amenorhea: bilateral primary ovarian Burkitt lymphoma.
AB  - OBJECTIVES: Burkitt's lymphoma (BL) occurs mostly in children. Isolated bilateral
      ovarian involvement presenting with amenorrhea is extremely rare in young adults.
      CASE: A 24-year-old female presented with secondary amenorrhea. Bilateral adnexal
      masses were identified on physical examination and abdominal computed tomography
      (CT). She underwent total abdominal histerectomy and bilateral
      salpingoophorectomy. Histopathologic evaluation yielded a diagnosis of BL of
      ovaries. Combined chemotherapy was administered. After complete remission an
      autologous bone marrow transplantation (ABMT) was performed. She died 35 days
      after ABMT. CONCLUSIONS: Although rare, BL should be kept in mind when isolated
      ovarian tumors are detected in young patients.

PMID- 14599884
TI  - Embryonal rhabdomyosarcoma of the uterine cervix: case report and review of the
      literature.
AB  - OBJECTIVES: Sarcoma botryoides rarely arises in the uterine cervix. It usually
      presents in the adolescent age group. The peak incidence is in the second decade.
      A combined modality approach to treating rhabdomyosarcoma (RMS) has markedly
      improved survival. We present two cases of cervical RMS. One of them had a very
      aggressive clinical course. CASE: Two cases of RMS in young women who presented
      with rapidly progressive cervical tumor are reported. They were treated with two
      stage surgical procedure and chemotherapy. CONCLUSIONS: A combined modality
      approach to treating RMS using multidrug chemotherapy, radiotherapy, and surgery
      has markedly improved survival. One of our cases has been free of disease for
      more than 5 years.

PMID- 14599885
TI  - Primitive neuroectodermal tumor of the vagina.
AB  - OBJECTIVES: Primitive neuroectodermal tumor is grouped together with Ewing
      sarcoma of the bone, but its presentation includes a wider age range and more
      central locations than its osseous counterpart. Presentation in vagina is
      exceedingly rare. CASE: A 34-year-old woman with personal history of kidney
      transplant presented with a painless vaginal mass. After surgical excision,
      pathology results demonstrated a primitive neuroectodermal tumor. Chemotherapy
      was given, followed by external beam and vaginal intracavitary brachytherapy.
      After 20 months postexcision, there is no clinical nor radiographic evidence of
      recurrence. CONCLUSIONS: This is the second case of primitive neuroectodermal
      tumor located in the vagina reported in the literature.

PMID- 14599886
TI  - Septation and cytokinesis in fungi.
AB  - Cytokinesis is the ultimate step of a cell cycle resulting in the generation of
      two progeny. Failure of correct cell division may be lethal for both, mother and
      daughter cells, and thus such a process must be tightly regulated with other
      events of the cell cycle. Differing solutions to the same problem have been
      developed in bacteria and plants while cytokinesis in animal and fungal cells is
      highly similar and requires a contractile ring containing actomyosin. Cytokinesis
      in fungi can be viewed as a three-stage process: (i) selection of a division
      site, (ii) orderly assembly of protein complexes, and finally (iii) dynamic
      events that lead to a constriction of the contractile ring and septum
      construction. Elaborate mechanisms known as the Mitotic Exit Network (MEN) and
      the Septation Initiation Network (SIN) have evolved to link these events,
      particularly the final steps of cytokinesis, with nuclear division. The purpose
      of this review was to discuss the latest developments in the fungal field and to
      describe the central known players required for key steps on the road to cell
      division. Differences in the cytokinesis of yeast-like fungi that result in
      complete cell separation in contrast to septation which leads to the
      compartmentalization of fungal hyphae are highlighted.

PMID- 14599888
TI  - The development of simple sequence repeat markers for Magnaporthe grisea and
      their integration into an established genetic linkage map.
AB  - Although microsatellite or simple sequence repeat (SSR) markers have several
      advantages, few have been developed in fungi. The goal of this study was to
      identify and characterize SSR-containing loci in the filamentous ascomycete
      Magnaporthe grisea, the causal agent of rice blast disease, and to add these
      markers to an integrated genetic map of this species [Theor. Appl. Genet. 95
      (1997) 20]. We have constructed and screened a microsatellite-enriched small
      insert genomic library as well as exploited both publicly available and one
      proprietary databases for identification of M. grisea SSR containing sequences.
      Twenty-four out of 49 primer pairs designed to amplify SSR, produced unambiguous
      polymorphic products in our test population of six isolates. The number of
      alleles at each locus ranged from two to six when assayed on 3% agarose gels.
      Twenty-three of the primer pairs amplified polymorphic products between Guy11 and
      2539, the parents of a cross from which a genetic map for M. grisea has been
      established. Genetic analysis showed that all the markers segregated in the
      expected 1:1 ratio and map positions were determined for all 23 loci.

PMID- 14599887
TI  - Characterization of the glucose-6-phosphate isomerase gene in Phytophthora
      infestans reveals the presence of multiple alleles.
AB  - Glucose-6-phosphate isomerase (GPI) plays a key role in both glycolysis and
      gluconeogenesis. Isoforms of GPI are common, and therefore, its isozyme pattern
      is widely used to characterize isolates of Phytophthora infestans. Despite the
      importance of GPI in P. infestans studies, the gene encoding this enzyme has not
      yet been characterized. Furthermore, it has been suggested that P. infestans
      contains multiple copies of the gene but this hypothesis remains to be
      demonstrated. We have cloned and characterized GPI in various isolates of P.
      infestans as well as in several species of the genus Phytophthora. The gene
      contains 1671bp and encodes a protein with a predicted molecular weight of
      60.8kDa. Multiple different alleles were identified and Southern analysis
      indicated certain P. infestans isolates carry several copies of the gene.
      Phylogenetic analysis revealed that P. infestans GPI is most closely related to
      sequences from Toxoplasma gondii, Arabidopsis thaliana, and Clarkia lewisii.

PMID- 14599889
TI  - Mapping and characterization of polymorphism in mtDNA of Cryphonectria
      parasitica: evidence of the presence of an optional intron.
AB  - The mitochondrial DNA (mtDNA) of the filamentous ascomycete Cryphonectria
      parasitica is large and polymorphic so, to better understand the nature of the
      polymorphisms within populations, a small collection of Italian strains of the
      fungus was examined. Known mtDNA polymorphisms were mapped and found to cluster
      in four regions of the mtDNA molecule, particularly in the RFLP region 2 where
      five different mtDNA haplotypes out of 13 strains were identified. This region
      included an area of 8.4kbp which was entirely sequenced in strain Ep155 showing
      the presence of two introns. An internal 3.2kbp portion was sequenced also in six
      additional strains. Sequence comparison of the C. parasitica mitochondrial
      intronic ORFs revealed similarities to known endonucleases such as those of
      Podospora anserina and Neurospora crassa. DNA sequence analysis showed that three
      polymorphisms of this mtDNA region within this population of 12 strains were due
      to the optional presence in the ND5 gene of an intron and of an intervening
      sequence within the intron. Evidence was also found within this population of
      mixed mitochondrial types within a single strain.

PMID- 14599890
TI  - Analysis of nutrient-dependent transcript variations in Neurospora crassa.
AB  - Nutrient-dependent variations in transcript levels of the filamentous fungus
      Neurospora crassa were studied on a microarray containing some 4700 cDNAs. Cells
      were grown in minimal and acetate medium. The isolated RNA was analyzed in
      comparison to the results obtained upon the hybridization of samples prepared
      from the RNA of cells grown in full medium. Altogether, 160 cDNA clones exhibited
      significant variations, falling into five distinct subgroups of very similar
      transcription profiles. This is indicative of the occurrence of a high degree of
      co-regulation of genes in N. crassa. Especially the regulation of the expression
      of proteins involved in metabolic pathways was found to be strongly regulated at
      the RNA level.

PMID- 14599891
TI  - Characterization of phiA, a gene essential for phialide development in
      Aspergillus nidulans.
AB  - We have previously identified genes and proteins involved in the fungal response
      to the Streptomyces-produced antibiotics, bafilomycin B1 and concanamycin A,
      known inhibitors of V-ATPases. Using mRNA differential display we identified an
      Aspergillus nidulans gene with 30-fold up-regulated expression in the presence of
      bafilomycin. This gene, here denoted phiA, and its gene product, were further
      characterized by targeted gene disruption and immunohistochemistry.
      Phenotypically, the phiA mutation resulted in reduced growth and severely reduced
      sporulation. The abnormality could be traced to the phialides, which divided
      several times instead of forming a single flask-shaped cell. The importance of
      phiA for phialide and conidium development was supported by immunohistochemistry
      experiments that showed the protein to be mainly present in these two cell types.
      Attempts to relate phiA to inhibition of V-ATPases did not result in unambiguous
      conclusions, but suggest the possibility that changed expression of phiA is
      correlated with growth arrest caused by inhibited V-ATPases.

PMID- 14599892
TI  - Role of the Mf1-1 pheromone precursor gene of the filamentous ascomycete
      Cryphonectria parasitica.
AB  - Site-directed recombination was used to obtain a Cryphonectria parasitica strain
      carrying deletions at the Mf1-1 gene locus. Macroscopic features such as growth
      rate and conidia production were unaffected by Mf1-1 deletions, but, when a
      strain containing a complete deletion of Mf1-1 was used as spermatia it was male
      sterile. The same strain was fully competent as a female parent. Deletion of
      three of the seven putative pheromone peptide repeats within the gene had no
      effect on mating. Male fertility of the complete deletion strain was restored
      when an ectopic copy of the Mf1-1 gene was returned by transformation. Expression
      of the mating type specific pheromone precursor gene Mf1-1 was stimulated by
      growth in nutritionally poor liquid media. It was found that age and source of
      inoculum of liquid cultures influences pheromone precusor gene expression, i.e.,
      conidia did not express Mf1-1 and cultures derived from conidia were
      significantly delayed in expression of this gene, as were cultures derived from
      young mycelium. Cultures inoculated with older hyphae, however, expressed Mf1-1
      within 1 day after inoculation.

PMID- 14599893
TI  - Structural features and evolutionary considerations of group IB introns in SSU
      rDNA of the lichen fungus Teloschistes.
AB  - Different species of the lichen-forming ascomycete fungus Teloschistes were found
      to contain group IB introns at position S1506 in the small subunit ribosomal RNA
      gene. We have characterized the structural organization and phylogeny of the
      Teloschistes introns Tco.S1506, Tla.S1506, and Tvi.S1506. Common features to all
      the introns are a small size, a compact RNA structure, and an atypical catalytic
      ribozyme core sequence motif. Variations in intron sizes, due to sequence
      extensions in the P1 and P8 loop segments, were observed in different species and
      isolates. Phylogenetic analyses based on the ITS1-5.8S-ITS2 region as well as the
      introns show that the Teloschistes S1506 introns represent a distinct
      evolutionary isolated cluster among the nuclear group I introns. Furthermore,
      introns from different lineages of Teloschistes villosus appear not strictly
      vertically inherited probably due to horizontal transfer in one of the lineages.

PMID- 14599894
TI  - Interaction of mutations affecting tip growth and branching in Neurospora.
AB  - There are at least 100 loci encoding products that influence tip growth and
      branching in Neurospora crassa. The functional relationships between 38 of these
      loci were examined by an analysis of gene interaction in double mutants. A
      complex range of interactions was revealed. These have been grouped into full and
      partial epistasis, costasis, novel phenotypes, and synthetic lethality and
      sublethality. Epistasis was used to construct the simplest "pathway" that
      accommodated the results; this pathway was Y-shaped. If synthetic sublethality is
      interpreted to reflect mutations in the same pathway, the sublethal connections
      are compatible with the chart of epistasis. The gene interactions discovered
      represent candidates for future cell and molecular studies on the interaction of
      gene products in the control of tip growth and branching.

PMID- 14599896
TI  - Addendum to "The pH-induced glycosylation of secreted phosphatases is mediated in
      Aspergillus nidulans by the regulatory gene pacC-dependent pathway" [Fungal
      Genet. Biol. 39 (2003) 286-295].

PMID- 14599895
TI  - Two divergent plasma membrane syntaxin-like SNAREs, nsyn1 and nsyn2, contribute
      to hyphal tip growth and other developmental processes in Neurospora crassa.
AB  - Highly polarized exocytosis of vesicles at hyphal apices is an essential
      requirement of tip growth. This requirement may be met by the localization and/or
      activation of an apical SNARE-based machinery. We have cloned nsyn1 and nsyn2,
      SNAREs predicted to function at the plasma membrane in Neurospora crassa.
      Transformation of extra copies of nsyn1 into wild-type strains displayed effects
      consistent with quelling of nsyn1 expression, which was lethal in most
      transformants. All surviving transformants grew slowly, conidiated poorly, and
      were male sterile. In addition, antisense nsyn1 strains grew slowly, with
      abnormal hyphal diameters and polarity and defective conidiation. For nsyn2,
      several repeat induced point mutation (RIP) crosses produced no, or poorly
      germinating ascospores. Those that germinated produced slow-growing hyphae with
      abnormal branching. The defects in nsyn1 and nsyn2 mutants are consistent with
      differential impaired vesicle fusion in hyphal tips and other developmental
      stages.

PMID- 14599898
TI  - [The therapeutic function of the aesthetic surgery].
AB  - By its definition and its etymology, aesthetic surgery is as much a surgery for
      the soul as for the body. Aesthetic surgery is a true "armed" therapy that
      essentially targets the psychology of the patient. This therapeutic "arsenal"
      preserves and/or restores the health of the patient according to its different
      aspects as defined by the World Health Organization. The plastic surgeon is
      always concerned about his patient as a whole, and as a human being, of whom he
      takes charge. Indeed there lies his specificity: He is as well a surgeon and a
      physician. We identify and analyze, in this chapter, the particular quality of
      patient-surgeon relationship on a surgical, psychological and juridical level. It
      is interesting to note that this collaboration results from a spontaneous
      convergence. The surgeon, the main interested figure, asserts himself mainly as a
      physician that is totally involved in a dialogue with his patient. He multiplies
      the interviews and he sharpens his clinical approach, and his own reactions, with
      regard to the demand for plastic surgery. The psychiatrist establishes the
      theoretical and practical aspects of the patient demand. The jurist, far from the
      barren dissertation of the law, reconsiders the environment of the demand and
      legitimates the generating wish: he insists on the necessary information but also
      on assuming responsibility. The therapeutic function of the plastic surgery
      appears essentially related to the success of a psychic repair solicited by the
      patient but that is scarcely specified by him as such, and of which he is, most
      probably, rarely fully aware. The process is to listen and to gather the
      information that guarantees mutual understanding. Plastic surgery is considered
      irreplaceable by many of our patients, and indisputable by us. It brings
      incomparable social and human fertility. It is, however, an ambitious and
      difficult project that is highly demanding. It is far from the impression of
      facility reflected by the media. Every actor of this scene, where the patient
      takes the center stage, must be aware of it.

PMID- 14599899
TI  - [Aesthetic surgery and history].
AB  - The history of aesthetic surgery is linked to that of the 20th century. The first
      operations allowed by the progress of anesthesia and asepsis are the correction
      of "prominent ears" by Ely then rhinoplasty with endonasal incision by Roe.
      Considered by some as a precursor and a quack by others, C.C. Miller was the
      first surgeon to specialize and write books on the subject. Before world war I,
      aesthetic surgery was seldom practiced and publications were few. The war was at
      the origin of several units of maxillo-facial surgery created for the huge number
      of casualties with face trauma due to trench warfare. Many of those who will
      become great names in plastic surgery operated in these units: Blair, Davis, Leon
      Dufourmentel, Virenque, Morestin and Gillies. After the war, American surgeons
      were regrouped in scientific societies. Plastic surgery was privileged and
      aesthetic surgery was lifted for "quacks". In France, several surgeons such as
      Suzanne Noel, Passot, Bourguet, Dartigues showed an important creativity and
      described several techniques that inspired recent ones. The Dujarier case
      discredited French aesthetic surgery but did not stop the creation of the first
      French Society of Plastic Surgery in 1930. World war II led to new orientations.
      In England, the East Grinstead center with Gillies and McIndoe during and after
      the war was at the origin of many vocations. After the war, many national and
      international societies of plastic surgery started to appear. The French Society
      of Plastic Surgery was born in 1952.

PMID- 14599900
TI  - [Aesthetic surgery and ethic].
AB  - Body image, in our consuming societies, became more and more important, and its
      new modelizations magnified by medias, strike the plastic surgeon with ethic
      questions. The author analyze the fundamental aspects of ethic in aesthetic
      surgery and their practical consequences for specialists who wish to practice
      surgery with the aim to improve physical and psychological comfort of their
      patients with maximum security.

PMID- 14599901
TI  - [Aesthetic surgery and public health].
AB  - The increasing number of requests for aesthetic surgery legitimately leads to the
      question of whether it can be covered by Public Health. If we look at the
      definition of the World Health Organization, the answer is without any doubt an
      affirmative one. However, economic considerations show that there is no social
      system in the world that covers aesthetic surgery, except for some definite
      interventions. Requests for aesthetic surgery occur in all social classes. It is
      a personal choice and a voluntary decision. It is no longer society who assists a
      sick or ill patient but it is the person that assumes the responsibility for
      himself.

PMID- 14599902
TI  - [Aesthetic surgeons and mediatic field].
AB  - Media alter our image; aesthetic surgery has become a good thing for journalists
      wanting a better TV audience. The standard plastic reconstructive and aesthetic
      surgeon does not recognize himself in most of the TV shows: operate prepuberic
      children, enhance buttocks and pectoralis muscles, struggle with transsexuals em
      leader What is become whim mammoplasties, abdominoplasties, face lifts? We are
      partially responsible for this mediatic lynchage because we do not occupy the
      mediatic field. The journalists, without any professional ethical code, make an
      object out of us. So now is the time of our uprising.

PMID- 14599903
TI  - [Is there a boundary between reconstructive and aesthetic surgery?].
AB  - Reconstructive and aesthetic surgery are the two closely bond facets of plastic
      surgery. The training, the techniques are the same, and limits are often
      difficult to define in many cases, intermixing indications. One should well
      explain to the lay public and to other doctors the complementarity of the two
      aspects of plastic surgery. One should also help the young plastic surgeons to be
      the best in reconstruction and embellishment.

PMID- 14599906
TI  - [Aesthetic surgery, psychic preparation].
AB  - The aesthetic surgery impacts the psychological picture of the body. The
      candidate must be prepared to this change in appearance. If not, the surgeon must
      suggest the psychological preparation, evaluating the risk of dissatisfaction, in
      order to allow the surgical and narcissistic success of his operation. The
      author, a psychiatric, beneficiary in a strong experience of a surgical
      assistance, develops the interest of such a preparation upon a period of about 15
      years (1988-2002).

PMID- 14599904
TI  - [Humanitarian aesthetic surgery].
AB  - Must a face be disfigured by a terrible tropical disease, in order to make us
      realise that the well being of our gesture is aesthetically acceptable? Must our
      reparative motivation remain the only trace of our skill and our humanity? During
      a plastic surgery mission, so-called humanitarian mission, can this surgery be
      aesthetic? Can aesthetic surgery be humanitarian? We learnt from aesthetic
      surgery on humanitarian missions, that aesthetic is only a technic to assist the
      reparation aspect. There is no need to justify aesthetic by reconstruction,
      because aesthetic belongs, in its entirety, to reparation. There is no need
      either to feel guilty, when our technical gesture is aesthetic, since what really
      motivates our intervention is not for us to decide. Is the reparation of the
      cleft lip of a little Asian girl, a reparation gesture or only an aesthetic
      approach? You may think that this will be a reparation gesture, because it will
      be more "popular" or because you will reconstruct the muscular belt. This child
      will most probably look for a more beautiful or aesthetic lip (in any case, she
      ignores the intricacies of facial growth principles). Therefore, it will be an
      aesthetic intervention. Never mind the motivation, since your technic will be the
      same, and you will try to do your very best and the most aesthetically you can.
      Only the very intention behind an intervention will decide whether it is an
      aesthetic or a plastic intervention, whereas your technical gesture will remain
      the same. All this illustrates that our definitions are of a minor importance,
      compared with the mere satisfaction of our little Asian girl, which, hopefully,
      will be a "beautiful" satisfaction. In fact, we have learnt not to do aesthetic
      surgery, but to give an aesthetic approach to our surgery, even during our
      humanitarian missions. The form aesthetic surgery will take is very subjective
      and only the final result will have the last say. Hopefully this surgical result
      will be aesthetically and humanly acceptable.

PMID- 14599907
TI  - [Aesthetic snapshot: study about cosmetic surgical procedures and complications].
AB  - A questionnaire was addressed to 600 members of the French Society of Plastic
      Reconstructive and Aesthetic Surgery. Out of 19,000 interventions, thanks to the
      analysis of 112 answers, we were able to get a good picture of the activity in
      aesthetic surgery, showing the number and type of complications experienced
      during each intervention. Cosmetic surgical procedure represents 35% of global
      surgical activity of the French plastic surgeon. The most frequent interventions
      are liposuction (19%), breast augmentation (16%), eye-lid surgery (14%),
      abdominoplasty (12%), mammaplasty (10%), facelift (10%) and rhinoplasty (8%). The
      techniques for which we register more than 10% of problems are: abdominoplasty
      and mammaplasty. The techniques for which we register between 5% and 10% of
      problems are: rhinoplasty, facelift and breast augmentation. The techniques for
      which we register less than 5% of problems are: liposuction and eye-lid surgery.
      On average, the most frequent cosmetic surgical procedures give rise to 7% of
      complications.

PMID- 14599908
TI  - [Aesthetic surgery, patient's opinion. Quantitative and qualitative analysis of
      the aesthetic surgery results of 481 survey responders and 50 records of
      "dissatisfied" patients].
AB  - INTRODUCTION: Plastic surgery operations have considerably increased in the past
      20 years. The media more and more often reflect dissatisfactions, if not outright
      "failures", which are very difficult to quantify. The few available studies
      suffer from significant defects (number of patients/authors' independence). Since
      1991 we have taken note of various levels of dissatisfaction among members of the
      AIME association with regard to their plastic surgery operations. We offer a
      contribution in the shape of a survey (quantitative) and an analysis
      (qualitative) of patients' records. MATERIAL AND METHOD: Survey questionnaire
      available on the internet site INFOESTH.com (quantitative) and analysis of 50
      dissatisfied patients' records received at the association (qualitative).
      RESULTS: The quantitative survey analysed 481 answers of which 431 from women
      (89.6%) and 50 from men (10.4%). Information was considered insufficient in 152
      of the cases (31.8%). Satisfaction rating after the operation: very good = 190
      cases (39.5%)/good = 110 cases (22.8%)/average = 60 cases (12.4%)/not very
      satisfactory = 53 cases (11%)/failed = 68 cases (14.1%). Would not undergo
      another operation = 89 cases. Will not recommend the operation to a friend = 112
      (23.3%). Qualitative analysis (records): 41 depressive cases (82%) and six
      dysmorphopathy cases (12%)/50 cases complaining of a lack of information.
      Patients complain about the denials of their practitioner and a lack of medical
      follow-up resulting in blocked communications, which do not encourage them to
      undergo a retouch operation. DISCUSSION: Despite recent efforts to improve
      information, it is still believed to be inadequate in 31% of cases in the survey
      and 100% of the cases on file. Satisfaction ratings "very good" and "good" only
      add up to 62% of answers in the survey, which contrasts strongly with the usual
      statistics (90-95%) issued by practitioners. Qualitative analysis of patient
      files: the prevalence of psychic distress after an unsatisfying operation is
      high, although it is not possible with depression to distinguish between pre
      existing and reactional pathology. If one considers that the aesthetic
      expectation is mostly psychological, the plastic surgery act should only be one
      of the aspects of a more global care of the patient. Otherwise, patients think
      they "buy" a result rather than an attempt at getting results. CONCLUSION: The
      responsibility of the surgeon brings with it obligations concerning the quality
      of his recommendations, of the patient information, of the surgeon's technical
      skills and of the patient's follow-up. The results of this investigation show
      that the improvement "tools" seem to be first of all the patients' selection and
      the quality of communication.

PMID- 14599909
TI  - [Aesthetic surgery, the liability].
AB  - Which are the specific risks for the plastic surgeons in aesthetic surgery? There
      are several: first of all, patients consult by desire and not because of health
      problems; it is often during difficult moments in their life (job loss.).
      Moreover, the surgeon must give the most complete information to the patient: he
      must describe the surgery, the risks (even the most exceptional ones). The
      surgeons have to "use the best practices": what does it mean? This sentence deals
      with the idea that the surgeons must have all the necessary skills to perform an
      aesthetic surgery and to ensure the cares after the operation (experience,
      diploma, staff, equipment.). They do not have to guarantee a result. As they do
      not operate in a hurry, they must renounce to a surgery if there is a doubt
      concerning the risk or the result the patient is waiting for. For years we have
      been observing that the requests for getting compensations have been left to
      drift for a lot of reasons (deception with the result, youth not found again.).
      The capacity to discover the real reasons of an aesthetic surgery, the listening,
      the courage to refuse to operate if the patient expects too much. depends on the
      surgeon (and insurer) future quiet. Despite all these precautions, we can notice
      that each surgeon is involved one time in a 4-years period: he will waste his
      time (forensic examinations.). As a conclusion, we can say that the respect of
      the rules of ethics is the key to battle against the increase of files in
      proceedings.

PMID- 14599910
TI  - [Aesthetic surgery: the Union].
AB  - The author reports an evaluation and a retrospective study of the union's
      different activities. A quality approach, a serious commitment, a high level of
      competence and an openness as seen in the brochure and on the web site are
      discussed. Survey results carried out on our patients, which explore the
      perception and image of cosmetic surgery, the methods of recruitment the
      reputation of the union and the degree of information received by the public are
      also discussed.

PMID- 14599911
TI  - [Set up in plastic and aesthetic surgery: personal experience].
AB  - The set up in liberal practice represents a real turning point in the
      professional life of a medical doctor. After more than 10 years under the
      hospital protection the objective is to create a structure, which is a real small
      company and the academic program does not offer any particular training
      corresponding to this important step. The author proposes to briefly relate his
      own experience and add few advice that will help the younger ones in their
      enterprise. It is necessary to properly reflect on several subjects before any
      decisions: location's choice, setup's mode (alone, with an associate or
      acquisition of existing clientele) and the choice of the surgical establishments.
      Other decisions are more personal as the decoration of the office, the
      computerizing, the assistant's recruitment and the orientation of the surgical
      activity. Our specialty presents several specificity that have to be properly
      evaluated and some choices do not have to necessarily correspond to an economic
      or demographic logic. The aesthetic surgery is democratizing itself and the
      request of surgery is in constant increase. We must then have a strong
      preparation and look forward to the future with serenity giving to ourselves
      every means for professional success.

PMID- 14599912
TI  - [Aesthetic surgery: realities of virtuality. On the influence of images, new
      information and communication technologies, and the internet].
AB  - Communication using images proves to be the superior way to persuade audiences.
      Thus, in cosmetic surgery, images are widely used to inform and to lure
      consumers. The superpower of visual communication is being bolstered by viewers'
      credulity, who never call into question the authenticity of photos as long as
      those photos are credible. Colorful digital images are broadcasted among
      scientific meetings, displayed in medical offices, and posted on the Internet.
      They generate a virtual world where cosmetic surgery is idealized: plastic
      surgeons are talented and handsome, operations are successful, and complications
      do not occur. We consider that digital imaging and the Internet should serve as a
      means to provide information that will ultimately strengthen the surgeon-patient
      relationship.

PMID- 14599913
TI  - [Volume and facial rejuvenation].
AB  - The request of care for facial aging has changed. Patients wish more and more a
      "natural" rejuvenation. The analysis of the different ways of aging shows that it
      is important to restore the mid-face volumes in order to obtain the fullness of
      youth. Numerous techniques have been used to increase the central volumes. After
      an historical study of the different methods, the authors present the new
      concepts that give a large place to lipostructure as described by Coleman. This
      technique can be used alone or in association with other techniques (lifting,
      collagen or other products injections...). The results are motivating; the
      process is simple and quick. The post-surgical oedemas are often important, but
      complications are exceptional. All these criteria correspond to current demands
      linked to aesthetic surgery considering medico-legal pressure. The future is
      based on the improvement of good grafts defining more precisely the factors of
      resorption of adipose graft tissues.

PMID- 14599914
TI  - [The face lifting].
AB  - The authors wanted to evoke the main steps of the "star" operation that is the
      face lifting. They also wanted to recall what had been done, what is being done
      and what has passed off. They also wanted to toss out some ideas concerning the
      future, knowing of course that it is unpredictable.

PMID- 14599915
TI  - [The plastic surgeon and the prevention of facial aging process].
AB  - The fight against aging is carried out on several levels: a healthy life, anti
      aging medicine as well as fight against aging symptoms. In our days, plastic
      surgeons anxious to find answers to the specific demands of their patients must
      invest themselves in other areas, to at least, acquire the knowledge or, to
      enable them to practice the necessary skills to meet those needs. Once it is
      agreed upon that a healthy life is the forerunner of any meaningful anti-aging
      program, the forceful demands of patients for anti-aging treatments must be
      treated with great care. This specialty is presently at an embryonic stage. Today
      the research is focused on providing the best well being while aging rather than
      stopping it. In addition, to date, certain hormonal treatments have not proven
      their efficacy and safety. As for the prevention of facial aging, the injection
      of botulinum toxin A presents the most advanced technique known. It acts on aging
      resulting from muscular hyperkinetics. Furthermore, because of increased
      hydration of the skin it delays actinic aging. This technique has lots of room
      for improvement: on the physician side by developing a better understanding of
      functional anatomy to target the injections to suit each patient's case, and on
      the supplier side by improvement of the product.

PMID- 14599916
TI  - [Aesthetic blepharoplasty].
AB  - Suzanne Noel, a pioneer of aesthetic surgery in Europe, first published her
      results with cosmetic blepharoplasty in 1926, in a book entitled: "The social
      role of aesthetic surgery". Paul Tessier further expanded the range and surgical
      possibilities of blepharoplasty by incorporating lateral canthopexies and
      underlying the importance of the craniofacial skeleton. Other authors in the 20th
      century brought their own technical refinements to this operation, such as the
      transconjunctival route, and various fat preserving modifications as well as
      lipostructure. The aim of this paper was to review the surgical approach to
      blepharoplasty, according to both historical and currently used protocols
      (including data gathered by questionnaires sent to eight French and foreign
      plastic surgical teams). A new perspective is proposed regarding the analysis of
      different morphological and ageing subtypes. The indication for individual
      surgical techniques stems from an accurate analysis of each patient according to
      anatomical categories. Pre-operative records before any orbito-palpebral surgery
      should include a full orthoptic and ophthalmological assessment, as well as high
      quality medical photographs. An increasing emphasis has developed recently upon
      the use of autologous fat harvested locally (septofat advancement), or from a
      distant site (lipostructure).

PMID- 14599917
TI  - [Baldness surgery].
AB  - Redistribution from hair-rich to hair-poor areas is the fundamental principle of
      baldness surgery. Success of hair transplantation is based on the fact that
      transplanted hair follicles will behave as they did in their original area and
      continue to grow. Three basic techniques are employed: scalp flaps, scalp
      reductions and hair grafts. Each technique has undergone considerable refinements
      answering to initial wrong results and criticisms. The typical doll-hair tufted
      effect of old macro-grafts has disappeared with micro-graft shift. The
      unaesthetic cheese-like Hippocratic crown donor defect aspect ended when
      harvesting a long strip of occipital hair bearing scalp. The posteriorly directed
      hair growth has disappeared by using superiorly based flaps. Respective
      indications and tension-free closure ensure that the incidence of necrosis is
      low. Limited results of old scalp reductions have decreased by testing
      preoperative laxity of the scalp and using extensive undermining of the scalp.
      The future may release on medical treatment avoiding dihydrotestosterone to act
      on genetically predisposed follicles avoiding miniaturization of the hair and
      baldness development. However, when baldness has appeared, as the hair follicle's
      culture is not actually effective, the state of art is still to plan a surgical
      strategy using successive stages of this large panel of techniques to reach a
      natural effect with the best hair orientation and density.

PMID- 14599918
TI  - [What do we control in mammaplasty for hypertrophic and/or ptotic breasts?].
AB  - A retrospective view on the history of mammaplasties for hypertrophic and/or
      ptotic breasts, shows its evolutive sense, in which we attempted to describe the
      main stages, avoiding to make a long "catalog". The first period (the longest)
      was marked by progresses concerning the control of vascular security of the
      areola and the nipple. That stage was essential by the fact it permitted to
      liberate the attention of surgeons for other questions: those concerning the
      shape of the breast, means of fixity and the long term evolution, quality and
      length of scars... In the continuity of this long evolution, each one of the
      authors presents a personal reflexion about the elements of control (and of
      course their limits!), developing some concepts as: the supra-medical pedicle for
      the vascular security, the advantage of the association mammaplasty and breast
      implant in the long term evolution and attentive post operative care to improve
      the quality of the scar (J.Ohana); the usefulness of a geometrical methodology-in
      which the importance of parameters as congruence and base of mammary gland
      conservation ("BAMACO") for shortening the scar without compromising the quality
      of the operated breast is demonstrated and with a relatively good stability of
      correction of the ptosis (-58% after 2 years) (R. Selinger).

PMID- 14599919
TI  - [Past, present and...future of breast implants].
AB  - The past of breast implants is well known, the techniques seem to be up to date
      and the future definitely optimistic. Breast implants have been at the top of the
      polemic due to their complications. Technical innovations allow plastic surgeons
      to choose adequate types of breast implants and also improve the innocuity of
      this surgery. Due to the last juridic reglementation and behaviour's evolution,
      breast augmentation will probably keep its place at the top.

PMID- 14599920
TI  - [Liposuction and liposculpture].
AB  - Liposuction set a watershed in the evolution of plastic and cosmetic surgery, by
      allowing permanent removal of excess fat localized underneath the skin. Many body
      areas, once considered as untouchable, are now accessible since liposuction grew
      superficial and circular. Liposuction, generating skin retraction, made shorter
      scars feasible in most cosmetic surgery procedures, and opened up the way to
      liposculpture of the face and the body. Constantly improving therapeutic means
      have been succeeding one another: use of sharp followed by blunt cannula,
      laser/ultrasound-assisted liposuction, as well as rotary and vibrating cannula:
      what will remain in a few years em leader ? It is today taken for granted, that
      liposuction, now becoming sculptured, cannot be ignored anymore, and numerous
      ongoing research studies ensure that it still has a long life ahead.

PMID- 14599921
TI  - [Outline surgery after massive weight lossing or gastroplasty].
AB  - The silhouette surgery in case of obesity or after gastroplasty and massive
      weight loss is near the usual outline surgery. However, many differences shall be
      well-known: more and more cases appear and demand is rapidly growing. The main
      demand for surgery is aesthetical improvement. The development of gastroplasty
      has greatly increased the demand of this outline surgery. At the beginning of
      gastroplasty, plastic surgeons sent pathological obeses to the first
      "gastroplastician" visceral surgeons. Now, after massive weight loss (over 60
      kg), general health is improved, but aesthetical aspect is often worsened; so the
      patients turn back to the plastic surgeons. The therapeutical program associated
      combined surgeries, for example: breast plasty and abdominoplasty performed
      during the same procedure or important and multilocular lipoaspirations. Large
      skin excess and persisting over weight influence surgical procedure. A strict
      preoperative planning is mandatory to obtain safe, quick and satisfying result.
      Preoperative informations concerning results and postoperative evolution (like,
      for example, the possibility of blood transfusion, infection and scars em leader
      ) are very important. Usually, five procedures will be necessary over a 3 or 4
      years period of time: abdominoplasty, body-lifting, arm and thigh-lifting, breast
      surgery for ptosis, hyper- or hypotrophia of the chest, lipoaspirations and, in a
      few cases, face lifting em leader. We describe this so particular outline
      surgery, its techniques and usual evolution.

PMID- 14599922
TI  - [Aesthetic surgery: the last word].

PMID- 14599923
TI  - Molecular therapy and prevention of hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in some
      areas of the world with an extremely poor prognosis. The major etiologic risk
      factors for HCC development include hepatitis B virus (HBV) and hepatitis C virus
      (HCV) infection, toxins (alcohol, aflatoxin B1) and various inherited metabolic
      liver diseases, such as hemochromatosis and alpha-1-antitrypsin deficiency.
      Central to the molecular pathogenesis of HCC are mutations of various genes and
      genetic/chromosomal instability that result from chronic liver disease and the
      associated enhanced liver cell regeneration and mitotic activity. Alterations in
      the structure or expression of several tumor suppressor genes and oncogenes have
      been described. In addition, mechanisms leading to genetic instability due to
      mismatch repair deficiency or chromosomal instability and aneuploidy due to
      defective chromosomal segregation appear to be involved. The prognosis of HCC
      patients is generally very poor. Most studies have shown a five-year survival
      rate of less than 5% in symptomatic patients. HCC has been found to be quite
      resistant to radio- or chemotherapy. Investigations of the natural history and
      clinical course of HCC revealed a long-term survival of patients only with small
      asymptomatic HCC that could be treated surgically or nonsurgically. For patients
      with advanced symptomatic HCC, novel therapeutic strategies such as gene therapy
      are urgently needed. Apart from exploring and refining new HCC treatment
      strategies, the implementation of the existing measures or the development of
      novel measures to prevent HCC is most important. Primary HCC prevention could
      have a major impact on the incidence of HCC. Further, secondary prevention of a
      local recurrence or of new HCC lesions in patients after successful surgical or
      nonsurgical HCC treatment is of paramount importance and is expected to
      significantly improve disease-free and overall survival rates of patients. Based
      on rapid scientific advances, molecular diagnosis, gene therapy and molecular
      prevention are becoming increasingly part of our patient management and will
      eventually complement or in part replace the existing diagnostic, therapeutic and
      preventive strategies. Overall, this should result in a reduced HCC incidence and
      an improved clinical outcome for patients with HCC, one of the most devastating
      malignancies worldwide.

PMID- 14599924
TI  - Comprehensive treatment for primary liver cancer.

PMID- 14599925
TI  - Liver transplantation for patients with viral hepatitis.
AB  - As a benign liver disease, end-stage viral hepatitis has been acknowledged as a
      main indication for liver transplantation. However, the recurrence of viral
      hepatitis is the major factor affecting the survival of transplant recipients.
      The recurrence of hepatitis B is defined as a return of positive HBsAg, while in
      case of hepatitis C, it is the return of positive HCV-RNA in serum. Several
      factors are believed as the hazardous factors of hepatitis recurrence, including
      the types and course of hepatitis, ethnical background, usage of antiviral drugs
      and immunosuppressive protocol. High dose, long term and combinative therapy of
      HBIg and novel drugs such as lamivudine and ribavirin offers the promising result
      of preventing hepatitis recurrence.

PMID- 14599926
TI  - Rheumatologic manifestations of hepatic diseases.
AB  - A possible link is suggested between hepatic diseases and rheumatic disease.
      Polyarthralgia and polyarthritis may be seen during the prodromal period of acute
      viral hepatitis, especially in hepatitis B virus (HBV). The symptoms of
      arthritis, mild, localized or generalized, mostly involve the small joints of
      hands. Joint symptoms frequently precede the onset of jaundice, no residual joint
      deformities. Circulating immune complexes are believed to play a causative role
      in the development of vasculitis and arthritis. Hemochromatosis is an antosomal
      recessive disorder of iron. About 43%-81% of patients with hemochromatosis have
      arthritis. The common extrahepatic manifestations of autoimmune hepatitis are
      arthralgia and skin rash. The reported prevalence of symptomatic inflammatory
      arthropathy in patients with primary biliary cirrhosis ranges from 4% to 50%.
      Skeletal involvement with Wilson's disease is common. Such patients may complain
      of pain and stiffness, mainly in the knee, wrist, or other large joints.
      Shwachman's syndrome is a disorder of pancreatic exocrine. Symmetric bone lesions
      have been reported in 10% to 15% of patients. They are involved predominantly at
      the femoral neck. Rheumatic symptoms are seen in one third of adult patients with
      cystic fibrosis and arthritis in 2.5% to 12% of patients. The arthritis caused by
      pancreatic panniculitis is usually symmetrical and involves the small joints of
      the hand, wrist, and feet, but may involve such larger joints as the elbow,
      ankle, and knee.

PMID- 14599928
TI  - Venovenous bypass ahead of mobilization of the liver in orthotopic liver
      transplantation.
AB  - BACKGROUND: To evaluate feasibility and safety of venovenous bypass prior to
      mobilization of the liver during orthotopic liver transplantation (OLT). METHODS:
      Fifty-four patients were classified into two groups. Group A consisted of 23
      patients receiving OLT with classical venovenous bypass. Group B consisted of 31
      patients who received a modified-procedure: venovenous bypass ahead of the
      mobilization of the liver during OLT. The blood loss, duration of venovenous
      bypass, cold ischemia time, anhepatic phase, and transfusion during operation in
      the two groups were compared. Complications after the operation were also
      compared between the two groups. RESULTS: The duration of venovenous bypass and
      cold ischemia time in group A were longer than those in group B [(99.78+/-21.36
      min) vs (96.32+/-22.25 min) and (484.78+/-134.01 min) vs (443.15+/- 85.27 min)].
      The anhepatic phase lasted for about 100 min averagely in the two groups. The
      volumes of blood loss and transfusion during the operation were larger in group A
      than in group B [(5096+/-4243 ml) vs (1726+/-1125 ml) and (3676+/-2938.74 ml) vs
      (1217.69+/-829.72 ml)]. Postoperative complications occurred in 26 patients of
      group A and in 19 patients of group B. CONCLUSION: This modified-procedure or
      venovenous bypass ahead of mobilization of the liver in OLT can reduce the blood
      loss during OLT and the incidence of postoperative complications without
      prolongation of the anhepatic phase and duration of venovenous bypass.

PMID- 14599927
TI  - Expression of 4-1BB molecule on peripheral blood T cells in liver transplanted
      patients and its clinical implication.
AB  - OBJECTIVE: To investigate the gene expression of 4-1BB in peripheral blood
      mononuclear cells (PBMCs) and its possible significance in clinical liver
      transplantation. METHODS: Reverse transcription-polymerase chain reaction (RT
      PCR) was used to determine the gene expression of 4-1BB in PBMCs from 22 patients
      receiving liver transplantation, 13 patients with primary liver carcinoma (PLC),
      and 12 healthy controls. To determine whether 4-1BB molecule is also expressed on
      the surface of CD4+ and CD8+ T cell, flow cytometry was used to analyse the
      phenotype of T cell subsets from the blood of liver transplantation patients.
      RESULTS: 4-1BB mRNA was detected in PBMCs from stable survivors after liver
      transplantation, but almost not detected in PBMCs from PLC patients and healthy
      controls. Meanwhile, 4-1BB was almost not expressed on the surface of CD4+ and
      CD8+T cells in healthy controls and PLC patients. A low level of 4-1BB
      expression, however, was found on the surface of CD4+ and CD8+ T cells from the
      stable survivors after liver transplantation. CONCLUSIONS: This study
      demonstrates that although patients are stable after liver transplantation,
      effector T-cells can also be activated through the signal of 4-1BB molecule and
      persistent immune response to grafts. Blockage of 4-1BB/4-1BBL pathway may
      benefitially reduce the clinical dosage of immunosuppressive agents and prolong
      the survival of grafts.

PMID- 14599929
TI  - Early prevention and treatment of biliary tract complications after orthotopic
      liver transplantation.
AB  - OBJECTIVE: To investigate the prevention and treatment of biliary complications
      after orthotopic liver transplantation (OLT). METHODS: OLT was performed in 18
      patients with end-stage liver disease, including 6 patients with primary liver
      cancer. Except 1 patient was infused only through the portal vein, others were
      infused through the portal vein and hepatic artery of the donor. The biliary
      tract was reconstructed using choledochocholedostomic anastomosis in 17 patients,
      and using Roux-en-Y choledochojejunostomic anastomosis in 1 patient. RESULTS:
      Four patients with biliary complication were found. In one patient, biliary
      leakage was found around the T-tube on day 14 postoperatively, and disappeared
      after re-opening of the tube. In one patient undergoing Roux-en-Y
      choledochojejunostomic anastomosis, biliary leakage was found on day 12
      postoperatively and reoperation was performed. The T-tube was removed from the
      anastomosis after reoperation, and abdominal infection was controlled, but high
      fever recurred on day 49 postoperatively. The patient died on day 52
      postoperatively. Autopsy revealed biliary leakage and biliary tract necrosis. In
      another patient, biliary leakage was found on day 3 after operation, and was
      treated by adequate drainage. Four months after operation, biliary sludge in the
      common tract was found and treated successfully with oral chemolysis. But biliary
      sludge or stone recur on one and half year after OLT. Spincterotomy and basket
      extraction were performed via endoscopic retrograde cholangiopancreatography, and
      the biliary sludge or stone was cleared out. In case 4, biliary drainage tube
      cholangiogram showed anastomotic stenosis one month after operation. Three months
      later, biliary sludge or stone was found beyond anastomotic stenosis. After oral
      chemolysis (ursodeoxycholic acid) and irrigation with heparinized saline solution
      via the biliary drainage tube, the biliary sludge disappeared. CONCLUSIONS: To
      reduce the incidence of biliary complications, adequate infusion of the hepatic
      artery, complete slushing of the biliary tract, and reduction of injury to the
      blood supply of the donor biliary tract are essential. Most biliary complications
      can be treated successfully by non-operative treatment or minimally invasive
      operation.

PMID- 14599930
TI  - The value of color Doppler ultrasonography in monitoring normal orthotopic liver
      transplantation and postoperative complications.
AB  - OBJECTIVE: To assess the value of color Doppler ultrasonography in monitoring
      normal orthotopic liver transplantation and postoperative complications. METHODS:
      Forty-one patients after orthotopic liver transplantation were examined by using
      color Doppler flow imaging to observe the hepatic blood flow and change of
      ultrasonography of the hepatic parenchyma and bile duct. The measured indexes
      included maximum blood flow velocity, time-average blood flow velocity (TAV),
      resistance index (RI) and diameter of the bile duct. RESULTS: Among 41 patients,
      17 (41.5%) suffered from liver transplant rejection. Of the 17 patients, 13
      (76.4%) showed decrease of TAV of the portal vein, 15 (88.25%) low-amplitude
      single-phase serrated wave or negative biphasic wave of the hepatic vein, 9
      (52.9%) increased hepatic arterial RI, and 5 (29.4%) slightly dilated bile duct.
      Sonography showed disappearance of the hepatic artery blood flow around the
      portal vein in 5 (12.2%) of the 41 patients with hepatic artery thrombosis in the
      postoperative period. Slight dilatation of the intrahepatic bile duct was found
      in 3 (7.3%) of the 41 patients in the early postoperational period and it
      normalized within 2 weeks. Ultrasonography of 20 patients (48.8%) revealed a
      visible dilatation of the intrahepatic bile duct, which was worsening gradually.
      The causes of bile duct dilatation included biliary stricture in 2 patients
      (10%), stone in 15 patients (75%) and others in 3 patients (15%). CONCLUSIONS:
      Color Doppler ultrasonography is valuable for monitoring normal liver
      transplantation and postoperative complications.

PMID- 14599931
TI  - Primary liver cancer in the elderly: report of 125 cases.
AB  - OBJECTIVES: To understand the characteristics of primary liver cancer (PLC) in
      the elderly and summarize the experience in treatment of such patients. METHODS:
      The clinical data of PLC in the elderly group (>/=60 years, 125 patients) and the
      young group (</=59 years, 295 patients) were analyzed retrospectively. RESULTS:
      In the elderly group, 64 patients were found HBsAg positive, 39 patients small
      PLC, 24 large PLC, 15 tumor emboli in the portal vein, 86 AFP positive, and 34
      hepatectomy performed. In the young group, 205 patients were found HBsAg
      positive, 79 patients small PLC, 97 large PLC, 96 tumor emboli in the portal
      vein, 200 AFP positive, and 126 hepatectomy performed. The median survival was 44
      and 25 months respectively, and no significant difference was observed in the
      mortality between the two groups (P>0.05). CONCLUSIONS: Hepatectomy is a choice
      of treatment for PLC in the elderly based on their liver function. AFP and B
      ultrasonography are important methods for the diagnosis of PLC in the elderly.

PMID- 14599933
TI  - Reasonable choice of surgical procedures for patients with portal hypertension.
AB  - OBJECTIVE: To assess individualized therapeutic protocol for patients with portal
      hypertension on the basis of accumulated knowledge about the mechanism of portal
      hypertension. DATA SOURCES: Patients data on shunt and other surgical procedures
      from Ruijin Hospital, Shanghai, China and the published papers. RESULTS: The
      direction of blood flow of the collateral vessels in the gastro-splenic region is
      an important factor in deciding surgical strategy because there is a close
      relationship between surgical risk and the classification of liver function.
      Clinically it is confirmed that each patient needs an individualized surgical
      procedure and that prophylactic operation is suitable for patients with
      splenomegaly, splenism associated with serious esophageal varices and hemorrhagic
      tendency under endoscopy but acceptable liver function. The shunt diameter (SD)
      (SD = 0.67 x PVD) is determined in our patients according to individualized
      hemodynamics. The rehemorrhagic rate after shunt being higher than that in others
      may be related to lesioned gastric mucosa caused by portal hypertension or
      bleeding and temporary melena. This finding is good for prevention of hepatic
      encephalopathy. The life quality and labor ability of patients will be improved
      because of hepatopetal flow in the portal vein. With strict indications for
      reoperation, selective operation is performed as soon as possible when hemorrhage
      is controlled conservatively and liver function improved. Once the patient with
      cirrhosis associated with portal hypertension is scheduled for liver
      transplantation, treatment of hemorrhage should aim to keep the patient in good
      condition and to avoid the protocol that may be disadvantageous to liver
      transplantation in the future. CONCLUSION: Surgical procedures for patients with
      portal hypertension should follow the principle of individualization. To obtain
      the best outcome, the choice of reasonable surgical procedure is expected.

PMID- 14599932
TI  - Diagnosis and treatment of hepatic cholangiocarcinoma: report of 52 cases.
AB  - OBJECTIVE: To summarize the experience in diagnosis and surgical treatment of
      hepatic cholangiocarcinoma. METHODS: Clinical features, diagnosis, surgical
      treatment and prognosis of 52 patients with hepatic cholangiocarcinoma treated at
      our hospital from 1993 to 2001 were retrospectively reviewed. RESULTS: The
      patients with hepatic cholangiocarcinoma accounted for 4.1% (52/1261) of the
      total patients with primary liver carcinoma encountered at this hospital. The
      ratio of male to female was 1.36:1 in this group. Some patients were complicated
      by hepatitis B (32.7%), hepatolith (34.6%), liver abscess (13.5%), cirrhosis
      (53.8%), and serum positivity for alpha-fetaprotein (21.2%). No typical clinical
      manifestations were present in all patients. The diagnostic rates of ultrasound
      examination and CT were 80.8% and 94.2%, respectively. The resection rate of
      hepatic cholangiocarcinoma was 48.1%; and the 1-, 3-, 5-year survival rates were
      48.1% (25/52), 30.8% (16/52), and 19.2% (10/52) respectively in this group. In
      resectable cases, the 1-, 3-, 5-year survival rats were 80.8% (20/25), 48.0%
      (12/25), 28.0% (7/25) respectively. Seven patients without cirrhosis who had
      received radical resection and intra-arterial chemotherapy survived for more than
      5 years. In unresectable 27 cases, only 5 survived over one year even if
      selective hepatic arterial embolism and perfusion chemotherapy were employed.
      CONCLUSIONS: No specific serum marker is found for hepatic cholangiocarcinoma. CT
      diagnosis is superior to ultrasonography. When a patient has already diagnosed as
      having hepatolith or liver abscess before operation and occupying lesion is seen
      intraoperatively, rapid pathological examination should be done for a fair
      judgement of the nature of the mass and a decision-making of operative protocol.
      The patient can survive well after curative resection. No matter whether hepatic
      cholangiocarcinoma is resectable of not, both selective hepatic arterial embolism
      and perfusion chemotherapy are valuable.

PMID- 14599934
TI  - Non-alcoholic fatty liver disease: the problems we are facing.
AB  - OBJECTIVE: To review the current state of research in non-alcoholic fatty liver
      disease (NAFLD). DATA RESOURCES: Searching Medline (1994-2002) and Chinese
      Medical Journals Index (1998- 2002) for articles on NAFLD. RESULTS: NAFLD is a
      new and challenging field with increasing recognition although its pathogenesis
      is poorly understood. "Two hits" hypothesis is still the leading theory guiding
      current research. CONCLUSIONS: Genetic study is a promising way that might lead
      to breakthrough in NAFLD research. NAFLD study in China is at an initial stage
      and there is a long way to go.

PMID- 14599935
TI  - Enzymes activity of intestinal grafts after liver small bowel transplantation in
      rats.
AB  - OBJECTIVES: To investigate the activity alterations of enzymes in intestine
      grafts after liver/small bowel transplantation in rats and the relations of these
      changes to immune rejection of grafts. METHODS: A model of liver/small bowel
      transplantation (LSBT) was established in closed colony SD and Wistar rats. The
      activity of enzymes including triphosphatase (ATPase), alkalinophosphatase (AKP),
      acytelcholinesterase (AchE), oxidesynthase (NOS) and monoamine oxidase (MAO) in
      bowel grafts was studied histochemically at regular postoperative intervals.
      RESULTS: The activity of enzymes in the wall of the grafts disappeared eventually
      in isolated small bowel transplantation (SBT) rats. In contrast, the activity in
      LSBT rats remained and recovered postoperatively. CONCLUSIONS: The rejection in
      grafted intestine could be prevented or delayed in LSBT rats. The changes in the
      activity of enzymes and neurons might be used to detect the rejection and
      function of the graft.

PMID- 14599936
TI  - The role of donor hepatocytes and/or splenocytes pre-injection in reducing islet
      xenotransplantation rejection.
AB  - OBJECTIVE: To observe the effect of tail vein injection with donor hepatocyte
      and/or splenocyte on islets xenotransplantation rejection. METHODS: New-born male
      pigs and BALB/C mice were selected as donors and recipients respectively. Islets
      xenotransplantation was performed in recipients just after the third time of tail
      vein injection with donor hepatocytes and/or splenocytes. Macrophage
      phagocytosis, NK killing activity, T lymphocyte transforming function of spleen
      cells, antibody forming function of B lymphocytes, and T lymphocyte subsets were
      taken to monitor transplantation rejection. The effects of this kind of
      transplantation were indicated as variation of blood glucose and survival days of
      recipients. RESULTS: Streptozotocin (STZ) succeeded in inducing diabetes mellitus
      models of mice. Pre-injection of donor hepatocytes, and splenocytes or their
      mixture via tail vein was effective in preventing donor islets transplantation
      from rejection, which was demonstrated by the mentioned immunological marks. And
      each group of transplantation could decrease the blood glucose of recipients and
      prolong the survival days. Pre-injection of mixture of donor hepatocytes and
      splenocytes was more effective in preventing rejection than pre-injection of
      donor hepatocytes or splenocytes separately. CONCLUSION: We propose that pre
      injection of donor hepatocytes, splenocytes separately or their mixture before
      donor islets transplantation is a good way to prevent rejection.

PMID- 14599937
TI  - Immune protection of auxiliary liver to other allograft: report of 3 cases.
AB  - OBJECTIVE: To assess the immune status of auxiliary liver transplantation and to
      clarify the immune protection of auxiliary liver to other allograft. METHODS:
      Immunological markers and pathological changes in 3 patients undergoing auxiliary
      liver transplantation were analysed. RESULTS: The lower the concentration of
      immunosuppressive agent, the less the rejection and the milder the intensity in
      the 3 patients. The function of allograft after auxiliary liver transplantation
      was excellent. CONCLUSIONS: Patients are in a low immune reaction state after
      auxiliary liver transplantation. Auxiliary liver can protect other allografts by
      related immunological mechanisms. The side-effects of low-concentration
      immunosuppressive agents on auxiliary liver and other allografts are mild.

PMID- 14599939
TI  - Pre-ligation of afflicted hepatic inflow and outflow blood vessels of lesioned
      liver lobe during hepatectomy.
AB  - OBJECTIVE: To compare the merits of hepatectomy after pre-ligation of the hepatic
      inflow and outflow blood vessels of the lesioned liver lobe with those of
      Pringle's maneuver. METHODS: A total of 68 patients were divided into two groups
      A and B. In the group A (n=38), Pringle's maneuver was employed, whereas in the
      group B (n=30), hepatectomy after pre-ligation of the hepatic inflow and outflow
      blood vessels of the lesioned side of the liver was used. Peri-operative blood
      loss, postoperative bleeding and drainage, time of liver function recovery as
      well as incidence of postoperative complications were compared between the 2
      groups. RESULTS: The mean perioperative blood loss, the mean amount of
      postoperative bleeding and drainage, the time of liver function recovery as well
      as incidence of postoperative complications were significantly higher in the
      group A than in the group B (P<0.01). CONCLUSION: Hepatectomy after pre-ligation
      of the hepatic inflow and outflow blood vessels of the lesioned side of the liver
      is superior to Pringle's maneuver.

PMID- 14599938
TI  - Argon supper-cryosurgery for patients with middle and late stage liver cancer.
AB  - OBJECTIVE: To assess the value of argon supper-cryosurgery for 42 patients with
      middle and late stage liver cancer. METHODS: Forty-two patients who had received
      argon supper-cryosurgery were analyzed retrospectively in terms of their clinical
      characteristics as well as the performance of argon supper-cryosurgery. RESULTS:
      All patients were ameliorated in symptoms shortly after the operation, including
      pain alleviation, psyche straightening up, alpha-fetoprotein descending or
      recovery. Jaundice occurred in 1 patient and intraabdominal hemorrhage in 2. The
      levels of aspartate transaminase and alanine transaminase in all patients were
      elevated 1 month after the operation, and normalized after protective therapy of
      the liver. No operative death was noted. CONCLUSIONS: Cold and heat reversed
      therapy of argon supper-cryosurgery can drastically destroy tumor tissue,
      especially the tumors which are too large to resect or close to the large
      vessels. It is applicable to increase the operative rate, decrease the operative
      death rate, and enlarge the therapeutic scope.

PMID- 14599940
TI  - Surgical excision of giant primary carcinoma in the medial liver lobe.
AB  - OBJECTIVE: To assess the techniques for surgical excision of giant primary
      carcinoma in the medial liver lobe. METHODS: Operative managements, complications
      and their causes during and after resection of giant carcinoma in the medial
      liver lobe were analyzed retrospectively in 166 cases treated from October 1996
      through December 2001. RESULTS: Of the 166 patients, 123 (74.1 %) underwent tumor
      resection and 43 (25.9 %) regular lobectomy, including left trilobectomy (8, 4.8
      %), medial lobectomy (21, 12.7 %), right anterior lobectomy (11, 6.6 %), and
      hemihepatectomy (3, 1.8 %). All patients were subjected to surgery with
      intermittent interruption of the first porta hepatis under normothermia. The
      total interruption time was 7-68 minutes and average time was 24.5 minutes. The
      maximum single interruption time was 41 minutes. Intraoperative blood loss was 50
      4000 ml, averaging 726 ml. The maximum blood transfusion was 5200 ml, averaging
      was 811 ml, and transfusion was not needed in 54 patients. Postoperative
      complications occurred in 9 patients (5.4%), of whom, 2 (1.2%) died of liver
      failure and acute respiratory distress syndrome respectively. CONCLUSIONS: An
      adequate reserve of liver function is a prerequisite for a smooth recovery after
      operation. Careful intraoperative management is crucial to decrease postoperative
      complications.

PMID- 14599941
TI  - The origin of blood supply for cavernous hemangioma of the liver.
AB  - OBJECTIVE: To investigate the origin of blood supply to cavernous hemangioma of
      the liver (CHL). METHODS: To observe the relation of cavernous hemangioma of the
      liver to the hepatic artery and portal vein, we performed serial selective
      hepatic arteriography in 22 patients. Five patients after ligation of the right
      hepatic arteries underwent portography and liver staining by injection of
      methylene blue into the portal veins and 2 patients had hepatic specimens
      resected, which were made into a model cast by filling the hepatic veins (yellow)
      and portal venous branches (blue) with methyl methacrylate after vascular lavage.
      RESULTS: Serial selective hepatic arteriography showed that hepatic arteries and
      hemangioma were displayed simultaneously, and that hemangioma was supplied by one
      to numerous arterial branches. In the portal phase of portography, contrast
      medium failed to enter the tumor and the intrahepatic branches of the portal vein
      were pushed aside by the tumor; in the liver parenchymal phase, however, the
      tumor appeared to be a low-density area. Hepatic arteriography and portography
      revealed that the fistula between the artery and portal vein may not be existed.
      The liver stained with methylene blue showed that the normal hepatic parenchyma
      could be stained with deep blue; in contrast, the tumor was not stained at all.
      The casting specimens showed that the eroded tumor left a round vacant area
      because of its total shedding, and no blue stained branches of the portal vein
      extended into the tumor. CONCLUSION: Blood supply of CHL may originate from the
      hepatic artery.

PMID- 14599942
TI  - Left hepatic vein: can be sutured and ligated blindly in left hepatectomy?
AB  - OBJECTIVE: To determine whether the anatomic characteristics of the left hepatic
      vein, middle hepatic vein and common trunk could influence the operation
      procedures of left hepatectomy. METHOD: Fifteen fresh human liver specimens were
      dissected and their anatomic characteristics were recorded. RESULTS: The left
      hepatic vein and middle hepatic vein formed the common trunk of 1.2+/-0.4 cm in
      length in the 15 liver specimens. The angle between the left hepatic vein and
      middle hepatic vein was 91+/-18.3 degree. CONCLUSION: The left hepatic vein
      should not be sutured and ligated blindly in left hepatectomy because there might
      be a potential damage to the middle hepatic vein.

PMID- 14599943
TI  - Lethality in mice infected with recombinant vaccinia virus expressing hepatitis C
      virus core protein.
AB  - OBJECTIVE: To establish a mouse model of HCV core expression and investigate the
      toxicity of HCV core protein or the possible pathogenic effects. METHODS: A
      series of vaccinia viral expression vectors were engineered to express 5' portion
      of HCV genes including 5' non-translated region (NTR), core protein, and portion
      of the E1 gene. These HCV sequences were fused to a luciferase reporter gene and
      inserted into a vaccinia virus expression vector (pSC11) adjacent to the vaccinia
      virus promoter, p7.5. The recombinant DNA constructs were packed into infectious
      recombinant chimeric viruses. The expression of HCV core protein was examined in
      cultured cells after infection with these viruses. Death of the infected mice was
      investigated by specific correlation to the expression of HCV core protein and
      its expression levels. RESULTS: The recombinant virus (VNCE-LUA) expressed HCV
      core protein and an envelopeluciferase fusion protein in cultured cells. When
      Balb/c mice were inoculated intraperitoneally with more than 10(7) pfu per mouse
      of VNCE-LUA, death occurred immediately. The mortality was dependent on the
      amount of VNCE-LUA virus inoculated. All mice inoculated with 3 x 10(8) pfu of
      VNCE-LUA died within 4 days of infection and 50% of mice inoculated with 3 x
      10(7) pfu of VNCE-LUA died within 7 days of infection. No death occurred in mice
      inoculated with 3 x 10(8) pfu of a control recombinant vaccinia virus, which
      expressed luciferase but not the HCV core and envelope proteins. Deletion of core
      sequences from VNCE-LUA rapidly reduced the mortality of infected mice whereas
      deletion of envelope sequence did not. SCID mice infected with VNCE-LUA died 2-3
      days after infection, suggesting that the HCV-core induced mortality is not
      dependent on host T- or B-cell responses to core protein. CONCLUSIONS: HCV core
      protein can be lethal to mice when expressed in vivo and this specific lethality
      is independent of T-cells or B-cells. The findings and model itself provide a
      useful tool for further investigation on potential pathological effects as well
      as the potential toxicity of the HCV core protein.

PMID- 14599944
TI  - Identification of a gene engineering antibody against cystic echinococcosis in
      liver.
AB  - OBJECTIVE: To identify a gene engineering antibody against cystic echinococcosis
      in liver. METHODS: A single chain of variable fragment of human antibodies
      (ScFvs) was selected from the library by using affinity selection technique with
      the recombinant antigen on solid surface. The positive clones were demonstrated
      by ELISA and their DNA sequences were also determined. RESULTS: The DNA sequence
      data showed that the antibody gene is composed of 768 bp. In addition, a specific
      combination capacity with recombinant Echinococcus granulosus antigen B (r-EgB)
      was demonstrated by ELISA. CONCLUSION: The obtained gene engineering antibody
      against r-EgB may have potential implications in immunological treatment and drug
      targeting delivery.

PMID- 14599945
TI  - Cloning and expression of cDNAs from hepatitis E virus structural gene.
AB  - OBJECTIVE: To obtain recombinant antigen for development of anti-HEV ELISA kit
      and vaccine against hepatitis E virus infection. METHODS: A 492 base cDNA was
      collected from 5-terminus of open reading frame 2 (ORF2) among epidemic hepatitis
      E virus (HEV) isolated from Xinjiang, Western China. The fragment was digested
      with BamH I and EcoR I, and inserted into vector pGEX-4T-3 which was also
      digested by the same enzyme. The recombinant plasmid was transformed into E.coli
      TG-1 and the fusion protein expressed was confirmed by Western blot analysis
      using serum of a patient with hepatitis E. RESULTS: The recombinant plasmid was
      identified and confirmed with enzyme digestion, polymerase chain reaction (PCR)
      and sequencing, respectively. A protein band of about 46 kDa was demonstrated by
      SDS-PAGE and designated GST-pORF2. The result of Western blot analysis suggested
      that the fusion protein reacted with anti-HEV positive sera at a dilution of
      1:100. CONCLUSION: The recombinant protein GST-pORF2 may be useful in developing
      anti-HEV ELISA kit and vaccine against hepatitis E virus infection.

PMID- 14599946
TI  - Salviae miltiorrhizae ameliorates cirrhosis and portal hypertension by inhibiting
      nitric oxide in cirrhotic rats.
AB  - OBJECTIVE: To determine the effect of Salviae miltiorrhizae on cirrhosis and
      portal hypertension by inhibiting nitric oxide synthase type II (NOSII) in rats.
      METHODS: Real time RT-PCR was used to detect the expression of NOSII mRNA. The
      enzymatic activity of nitric oxide synthase and the circulating levels of nitric
      oxide (NO), systemic and portal hemodynamics, and quantification of cirrhosis
      were measured with highly sensitive methods. Traditional Chinese medicine was
      utilized to treat cirrhotic rats and the function of NO was evaluated. Double
      blind method was applied in the experiment constantly. RESULTS: The concentration
      of NO increased markedly at all stages of cirrhosis, and so did the enzymatic
      activity of NOS, and the iNOSmRNA expressed greatly. Meanwhile the portal-venous
      pressure (PVP), portal-venous-flow (PVF) increased significantly. NO, NOS and
      iNOSmRNA were positively correlated to the quantity of hepatic fibrosis. Salviae
      miltiorrhizae significantly inhibited NO production and inhibited the expression
      of iNOSmRNA. CONCLUSIONS: The increased hepatic expression of NOSII is one of the
      important factors causing cirrhosis and portal hypertension. Salviae
      miltiorrhizae significantly ameliorates cirrhosis and portal hypertension.

PMID- 14599947
TI  - Clinical significance of mrp gene in primary hepatocellular carcinoma.
AB  - OBJECTIVE: To study the relations among the expression of the multidrug
      resistance associated-protein (mrp) gene and clinicopathologic features, the
      influence of alpha-fetoprotein (AFP), and prognosis of patients who received
      adjuvant chemotherapy after resection of primary hepatocellular carcinoma (HCC).
      METHODS: The expression of the mrp gene encoding MRP and mRNAmrp was determined
      in tissues from 54 untreated patients with HCC, adjacent tissues from 24 patients
      with HCC and archival paraffin-embedded tissues from 12 patients with posthepatic
      cirrhosis. The relationship between the mrp gene expression and the change level
      of AFP was analyzed in the 24 postoperative HCC patients whose AFP level was
      measured after 2 weeks. All of the HCC patients were followed up. RESULTS: The
      percentage of positive expressions of MRP and mRNAmrp in the three kinds of
      tissues was 57.40%, 25.00%, 16.67%, and 72.22%, 37.50%, 33.33% respectively.
      Significant difference was noted in the untreated HCC tissue, compared to the
      other two tissues (P<0.05). No difference existed between the mrp gene expression
      and such clinicopathologic findings, as age, sex, and tumor size (P> 0.05), but
      the expression was related to the degree of differentiation of HCC (P<0.05). The
      effective rate of AFP in the mrp gene positive expression group or postoperative
      chemotherapeutic patients was lower than that in the negative group (P<0.05).
      Although no difference was seen in the 1-, 3-, 5-year survival rates of HCC
      patients (P>0.05), the mean survival time of postoperative HCC patients or the
      negative mrp gene expression group was longer than that of the positive group
      (P<0.05). CONCLUSIONS: Multidrug resistance (MDR) of HCC is related to mrp gene
      expression and initiates the intrinsic MDR. Detection of mrp gene expression is
      of great significance in accessing chemotherapeutic resistance of HCC, which
      provides evidence for reversing MDR in HCC. The mrp gene may be a useful marker
      in detecting prognosis of HCC patients because its expression is correlated with
      tumor differention and mean survival time of the patients.

PMID- 14599948
TI  - Effect of octreotide on angiogenesis induced by hepatocellular carcinoma in vivo.
AB  - OBJECTIVE: To investigate the effect of somatostatin analogue octreotide on
      angiogenesis induced by hepatocellular carcinoma (HCC) in vivo. METHODS: LCI-D20
      corneal micropocket model in nude mouse was used to dynamically observe
      angiogenesis under a stereoscopic zoom microscope and a digital camera system and
      to evaluate the effect of octreotide on angiogenesis. Male nude mice were
      subcutaneously implanted with LCI-D20 tumor tissues for tumor xenograft studies.
      Microvessel density in CD34-stained tumor sections was analyzed by
      immunohistochemical SP method. RESULTS: Tumor tissues from LCI-D20 implanted into
      the corneal micropocket induced angiogenesis. When animals received systemic
      octreotide treatment, angiogenesis response in the cornea of mice was moderate,
      the appearance of vascular buds was delayed, and the new capillaries were sparse
      and grew slowly. Compared with the control group, the neovascularization induced
      by HCC in the cornea of mice was markedly inhibited on day 7, 9, 12, 15, 18 and
      21 after implantation in the octreotide-treated group (P<0.05). Systemic
      administration of octreotide produced a significant suppression of the growth of
      LCI-D20. Immunohistochemical studies of tumor tissues revealed decreased
      microvessel density in the octreotide-treated animals as compared with the
      controls (21.7+/-4.27 versus 31.8+/-3.87, P<0.01). CONCLUSION: Somatostatin
      analogue octreotide is able to inhibit angiogenesis induced by HCC in vivo and
      may provide a new approach to the treatment of HCC.

PMID- 14599949
TI  - The effect of mycophenolate acid on hepatitis B virus replication in vitro.
AB  - OBJECTIVE: To use 2.2.15 cell line to determine the effects of mycophenolate acid
      (MPA) on hepatitis B virus (HBV) replication and viral protein synthesis in
      vitro. METHODS: The 2.2.15 cells were treated with different concentration of MPA
      (1-50 mug/ml) for 12 days. HBsAg and HBeAg were detected in the supernatant fluid
      by ELISA and intracellular HBV DNA was analyzed quantitatively by slot blot
      hybridization. RESULTS: MPA could suppress the expression of HBsAg and HBeAg, and
      the higher concentration of MPA induced lower expression of HBsAg and HBeAg. The
      suppression rates of MPA for HBsAg and HBeAg at a concentration of 50
      micrograms/ml were 34.2% and 24.1% respectively. The expression of HBV DNA was
      only 49% as compared with controls when treated with MPA at a concentration of 50
      micrograms/ml. CONCLUSIONS: Mycophenolate acid can suppress the expression of
      HBsAg and HBeAg as well as the replication of HBV DNA in the 2.2.15 cell. The
      suppressive degree is dose-dependent.

PMID- 14599950
TI  - Nested RT-PCR in detection of blood AFPmRNA in animal model of human
      hepatocellular carcinoma.
AB  - OBJECTIVES: To detect blood AFPmRNA in the nude mice bearing with human
      hepatocellular carcinoma (HCC) by using nested reverse transcriptase polymerase
      chain reaction (nested RT-PCR), and assess its significance in HCC distant
      metastasis. METHOD: We detected 20 blood samples from the nude mice bearing with
      human HCC by nested RT-PCR to find out AFPmRNA. RESULT: AFPmRNA was detected in 6
      blood samples from the nude mice bearing with human HCC (30.0%), in which 4 mice
      developed distant metastasis. CONCLUSION: AFPmRNA may be used as an efficient and
      sensitive marker to detect blood spread of HCC cells. It can predict the
      occurrence of HCC distant metastasis.

PMID- 14599951
TI  - HBV DNA level and antigen concentration in evaluating liver damage of patients
      with chronic hepatitis B.
AB  - OBJECTIVE: To investigate the correlations between HBV DNA levels and viral
      antigen concentrations in patients with chronic hepatitis B and their
      significance in clinical practice. METHODS: The HBV DNA levels and serological
      markers of 118 patients with chronic hepatitis B and 87 patients with liver
      cirrhosis who had not been treated with antiviral drugs were determined as well
      as the other parameters relevant to liver function. RESULTS: The HBV DNA levels
      of the patients with chronic hepatitis and cirrhosis were expressed as geometric
      mean+/-SD, 3.83 x 10(6)+/-1.34 copies/ml and 6.98 x 10(5)+/-1.29 copies/ml, and
      their HBeAg concentrations expressed as the luminescent values rate of sample to
      control (s/co) were 35.40+/-1.26 and 4.05+/-1.28, respectively. The HBV DNA
      levels in HBeAg positive group were significantly higher than those in HBeAg
      negative group (P<0.0001). The correlation coefficient between HBV DNA level and
      HBeAg or HBsAg concentration was only 0.273 and -0.12. During the recovery of
      hepatic function, the reduction of ALT or AST in patients with high viral content
      was significantly lower than that in patients with low viral content. No
      correlation was observed between HBV DNA and ALT levels. CONCLUSION: There are
      significant correlations between HBV DNA level and HBeAg concentration, but the
      coefficient is lower. HBV DNA level is not significantly related to ALT, but it
      could affect the recovery of liver function.

PMID- 14599952
TI  - A rat model for acute hepatic failure.
AB  - OBJECTIVE: To develop a surgical model of acute hepatic failure. METHODS:
      Hepatectomy was performed in rats according to the method described by Higgins
      and Anderson. Ninety percent liver resection (removing the left lateral, median,
      and right lateral lobes) (n=7) and 95% liver resection leaving only half of the
      caudate lobe (n=13) were performed. Hypoglycemia was corrected by giving 20%
      glucose in the drinking water, coupled with repeated intraperitoneal injection of
      5% glucose adapted to glycemia. While the survival rate, alanine transaminase
      (ALT) and bilirubin were observed. RESULTS: 95% liver resection decreased
      survival rates of the rats from 86% (90% liver resection) to 23% (P<0.05), and
      increased bilirubin levels (4.04+/-2.84 mg/dL vs. 1.25+/-1.85 mg/dL [90% liver
      resection]). CONCLUSION: 95% liver resection is a good rat model for acute
      hepatic failure.

PMID- 14599953
TI  - Effects of different drainage procedures on levels of serum endotoxin and tumor
      necrosis factor in patients with malignant obstructive jaundice.
AB  - OBJECTIVE: To assess the influence of different drainage procedures on the levels
      of serum endotoxin and tumor necrosis factor (TNF) in patients with malignant
      obstructive jaundice (MOJ). METHODS: The levels of endotoxin and TNF in 46
      patients with MOJ were measured before and after cholangiojejunostomy (CJ) or
      external bile drainage (EBD). RESULTS: In the CJ group, the levels of
      postoperative serum endotoxin and TNF 10 days after operation were significantly
      lower than those before operation (P<0.01). In the EBD group, no significant
      changes were observed in endotoxin and TNF levels before and after operation
      (P>0.05). No significant differences were seen between the two groups before
      operation (P>0.05), but the levels of endotoxin and TNF in the CJ group were
      significantly lower than those in the EBD group after operation (P<0.01).
      CONCLUSIONS: Cholangiojejunostomy other than external bile drainage can decrease
      the levels of serum endotoxin and TNF effectively, although both of them are able
      to release jaundice. Cholangiojejunostomy should be performed as soon as possible
      for patients with unresectable malignant tumor.

PMID- 14599955
TI  - Surgical mortality in patients with malignant obstructive jaundice: a
      multivariate discriminant analysis.
AB  - OBJECTIVE: To estimate the operative mortality in patients with malignant
      obstructive jaundice. METHODS: Twelve risk factors were analyzed using
      multivariate discriminant analysis in 90 patients who had been operated on.
      RESULTS: Operative mortality was significantly related to the following factors:
      age, duration of jaundice, packed RBC volume, white blood cell count and
      concentration of blood urine nitrogen; it was not significantly related to
      diseases and types of operation. The following formula was obtained: packed RBC
      volume x 0.09954-age x 0.04018- blood urine nitrogen x 0.23693-duration of
      jaundice x 2.07388-WBC count x 0.21118+ 5.26593. With this formula, an operative
      mortality of 77.8% was predicted. CONCLUSION: With a positive value from the
      formula, the patient should be operated on; otherwise non-operative treatment is
      advocated.

PMID- 14599954
TI  - Bile anaerobic bacteria detection and antibiotic susceptibility in patients with
      gallstone.
AB  - OBJECTIVE: To detect bile anaerobic bacteria and antibiotic susceptibility in 59
      patients with gallstones who had had cholecystectomy. METHODS: BACT/ALERT 120
      microbe detection system and SCEPTOR microbe detection system were used to detect
      bile anaerobic bacteria, antibiotic susceptibility. RESULTS: The ratio of
      anaerobic bacteria to the patients examined was 52.5% (31/59). Obligate anaerobe
      bile culture showed positive results in 4 patients. B. fragilis (37.8%) was the
      major type of anaerobic bacteria in bile. Most (81.8%) of anaerobic bacteria were
      sensitive to metronidazole, and imipenem was suitable for beta-lactamase
      bacteria. CONCLUSIONS: Culture of anaerobic bacteria in logarithmic phase can
      improve the positive rate of the culture. There are some relations between
      anaerobic infection and gallstone formation.

PMID- 14599956
TI  - Three-dimensional identification of the cystic infundibulum-cystic duct junction:
      a technique for identification of the cystic duct in laparoscopic
      cholecystectomy.
AB  - OBJECTIVE: The main cause of bile duct injury (BDI) at laparoscopic
      cholecystectomy is misidentification of the common bile duct as the cystic duct
      (CD). The aim of this article is to introduce a modified technique, i.e., three
      dimensional identification of the cystic infundibulum (CI)-CD junction, to
      prevent misidentification-induced BDI during laparoscopic cholecystectomy.
      METHODS: The CI was extensively dissected to expose its anterior, interior
      superior and inferior-dorsal aspects. With the CI nearly circularly dissected
      out, the CI and the appearance-indicated CI-CD junction might be three
      dimensionally identified and the reality of the CI-CD junction as well as the
      reality of the CD could be precisely judged. RESULTS: Overall 10 BDIs were
      documented in this group. Since BDI occurred in 8 of 4382 patients receiving
      laparoscopic cholecystectomy, the technique for prevention of misidentification
      induced BDI was established. Among the late batch of 7618 patients, only two BDIs
      were noted. CONCLUSIONS: Three-dimensional identification of the CI-CD junction
      is a reliable, feasible and relatively low experience-dependent technique to
      prevent most of misidentification-induced BDI.

PMID- 14599957
TI  - Diagnosis and treatment of chronic pancreatitis.
AB  - OBJECTIVE: To summarize our experience in treatment of chronic pancreatitis (CP).
      METHODS: Clinical data on 245 patients with CP treated at our hospital from May
      1983 to October 2001 were reviewed. RESULTS: Of the 245 patients, 122 suffered
      from CP for a year (49.8%) and 191 for 5 years (78.0%). The rate of positive
      diagnosis of B-ultrasound, CT, ERCP, B2-Ty-Para-aminobenzoic acid (PABA) for CP
      was 74.2%, 80.7%, 76.5% and 72.8%, respectively. 169 patients (69.0%) received
      surgical treatment. After the operation, 98.8% of the 169 patients experienced
      decreased pain with a complication rate of 1.2%. CONCLUSION: Early diagnosis and
      appropriate operative time and management are of vital importance in improving
      patients'quality of life and controlling the natural history of the disease.

PMID- 14599958
TI  - Clinical application of 13C-Hiolein breath test in assessing pancreatic exocrine
      insufficiency.
AB  - OBJECTIVE: To examine the feasibility and significance of 13C-Hiolein breath test
      in evaluating chronic pancreatitis-related exocrine insufficiency and efficacy of
      enzyme treatment. METHODS: The 13C-Hiolein breath test was used in 8 healthy
      volunteers (group 1), 8 chronic pancreatitis (CP) patients without steatorrhea
      (group 2), and 8 CP patients with steatorrhea (group 3). To evaluate the function
      of pancreatic exocrine, 13CO2 was determined following 13C-Hiolein diet. The 13C
      Hiolein test was repeated in group 3 after enzyme supplement therapy. RESULTS:
      Administration of 13C-Hiolein diet resulted in significantly higher cumulative
      percent dose of 13C recovery per 6 h (cPDR/6 h) and maximal PDR (PDR(peak)) in
      the healthy controls (group 1) than the CP patients with steatorrhea (group 3)
      (11.22%+/-1.22% and 6.11%+/-0.59% vs 2.87%+/-0.73% and 1.53%+/-0.36%,
      respectively, both P<0.01). In the CP patients with steatorrhea (group 3), a
      repeated test after enzyme supplementation therapy showed a significant elevation
      of both cPDR/6 h and PDR(peak) (9.03%+/-0.84% and 2.33%+/-0.47%, both P<0.01
      compared with those before enzyme treatment), but cPDR/6 h remained significantly
      lower than that in the healthy volunteers (group 1, P<0.05). Both cPDR and
      PDR(peak) in the CP patients without steatorrhea (group 2) were similar to those
      in the healthy controls (group 1, both P>0.05). CONCLUSION: The results of 13C
      Hiolein breath test well reflect fat metabolism status in CP patients, and the
      test can be used to monitor the efficacy of pancreatic enzymes therapy.

PMID- 14599959
TI  - Risk factors influencing mortality of patients with severe acute pancreatitis
      within 24 hours after admission.
AB  - OBJECTIVE: To study the risk factors for death of patients with severe acute
      pancreatitis (SAP) within 24 hours after admission. METHODS: Clinical and
      laboratory data of 74 patients with SAP were analyzed retrospectively. The 27
      possible risk factors for death within 24 hours after admission were investigated
      using logistic regression (SPSS software package 10.0), and the equation of
      logistic regression was set up. RESULTS: Among the 27 possible risk factors,
      arterial pH, APACHE II scores, early shock, multiple organ failure were
      associated with mortality. Single logistic regression analysis of the 27
      parameters showed that early shock, pleural effusion, arterial pH, complications
      and APACHE II scores were associated with death of SAP patients, but using
      multiple logistic regression analysis showed that only acidosis (pH<7.35) was
      associated with death. CONCLUSION: To maintain the function of organs and correct
      dysequilibrium of water-electrolyte and acid-base in early treatment of SAP is
      essential to lower the mortality.

PMID- 14599960
TI  - The role of inflammatory mediators in severe acute pancreatitis and regulation of
      glucocorticoids.
AB  - OBJECTIVE: To investigate the effect of glucocorticoids on systemic inflammatory
      mediator release in rats with acute pancreatitis and the outcome of dexamethasone
      in treatment of acute pancreatitis. METHODS: Sixty-eight Wistar rats were divided
      into sham, acute pancreatitis, and treatment (intravenous dexamethasone 0.5
      mg/kg) groups. Experimental acute pancreatitis was induced by the injection of 5%
      sodium taurocholate (0.1 ml/100 mg body weight) into the pancreatic-biliary duct.
      The blood samples were obtained and examined for 6-keto-PGI1alpha, TXB2 and IL-6
      postoperatively at 3, 6 and 12 hours, respectively. The pancreatic samples were
      evaluated by a blinded method. Twelve-hour survival rate was determined and
      compared between the groups. RESULTS: The high serum concentrations of 6-keto
      PGI1alpha, TXB2 and IL-6 were noted in the rats with acute pancreatitis
      associated with pancreatic hemorrhage and necrosis. Their 12-hour survival rate
      was 42.9%. The rats in the treatment group survived with significantly reduced
      serum concentrations of 6-keto-PGI1alpha, TXB2 and IL-6 (P<0.05). Their
      pancreatic morphology was normal. CONCLUSION: Dexamethasone may reduce the serum
      concentration of 6-keto-PGI1alpha, TXB2, and IL-6, and the severity of acute
      pancreatitis while increasing the survival rate of rats with acute pancreatitis.

PMID- 14599962
TI  - Analysis of gene expression profiles in pancreatic carcinoma by using cDNA
      microarray.
AB  - OBJECTIVES: To survey the gene expression profiles in pancreatic carcinoma by
      using cDNA microarray and detect target genes for further study. METHODS: Three
      mixed samples from 2 cases of normal pancreatic tissue and 4 cases of moderate
      differentiated pancreatic carcinoma were studied by means of cDNA microarray
      consisting of 18 000 genes. RESULTS: 1484 and 1353 different expressed genes were
      observed in two cancer samples respectively. We identified 455 genes altered with
      the same tendency in both samples, including 102 up-regulated and 353 down
      regulated genes. There were 274 known genes and 181 unknown genes; 27.8% and
      52.0% genes respectively had an expression level in cancer that was 2-fold higher
      or lower than that in normal samples. Tumor suppressor genes, growth factors and
      receptor genes, signal conduction genes, transcription factor genes were
      identified. CONCLUSIONS: cDNA microarray is an efficient and high-throughout
      method to investigate gene expression profiles in pancreatic carcinoma. MBD1,
      EDG1 and gene hypermethylation mechanism would play an important role in the
      pathogenesis of pancreatic carcinoma.

PMID- 14599961
TI  - Expression of platelet endothelial cell adhesion molecule-1 between pancreatic
      microcirculation and peripheral circulation in rats with acute edematous
      pancreatitis.
AB  - OBJECTIVE: To study the changes of platelet endothelial cell adhesion molecule-1
      (PECAM-1) expression on polymorphonuclear leukocytes (PMNs) in peripheral
      circulation and pancreatic microcirculation in rats with acute edematous
      pancreatitis (AEP). METHODS: The model of AEP was established with 50 Wistar
      rats, and the changes of PECAM-1 expression on PMNs from the splenic vein and
      inferior vena cava were determined by flow cytometry. RESULTS: PECAM-1 expression
      on PMNs showed no significant difference between pancreatic microcirculation and
      peripheral circulation at AEP2h and AEP4h time points. From the AEP4h to the
      AEP8h time point, PECAM-1 expression in peripheral circulation was up-regulated,
      but PECAM-1 expression in pancreatic microcirculation was down-regulated. PECAM-1
      expression had a significant difference between pancreatic microcirculation and
      peripheral circulation at the AEP8h time point (P<0.05). CONCLUSION: PECAM-1
      expression on PMNs is in a converse way between pancreatic microcirculation and
      peripheral circulation in AEP.

PMID- 14599963
TI  - Relationship between expressions of E-cadherin and alpha-catenin and biological
      behaviors of human pancreatic cancer.
AB  - OBJECTIVES: To investigate the expressions of E-cadherin and alpha-catenin in
      pancreatic carcinoma and their relationship with biological behaviors, and
      clarify the mechanism of invasion and metastasis of pancreatic cancer. METHODS:
      The expressions of E-cadherin and alpha-catenin was examined in 47 patients with
      infiltrative ductal adenocarcinoma of the pancreas and 12 specimens of normal
      pancreatic tissues by immunohistochemical technique (PicTure( trade mark ) two
      step method). Proliferation cell nuclear antigen (PCNA) was tested as an index of
      the proliferation degree of pancreatic cancer cells. RESULTS: The
      immunoreactivity of E-cadherin and alpha-catenin was expressed by normal ductal
      and acinar cells with strong membranous staining at the intercellular border in
      12 specimens of normal pancreatic tissues. The abnormal rate of E-cadherin
      expression in pancreatic cancer was 53.2% (25/47), and it was significantly
      related to differentiation, high proliferation degree and lymph node and liver
      metastases (P<0.01, 0.05, 0.05 and 0.01, respectively). 61.7% patients with
      pancreatic cancer (29/47) showed abnormal expression of alpha-catenin. There was
      a good correlation among alpha-catenin expression, histological grade, and lymph
      node and liver metastases (P<0.05,0.05 and 0.01, respectively). No significant
      association was found among abnormal expressions of E-cadherin and alpha-catenin,
      tumor size, invasion, and 1-year survival rate of patients (P>0.05, all). There
      was a positive relationship between the expressions of E-cadherin and alpha
      catenin in the 47 patients with pancreatic cancer (P<0.01, r=0.88). CONCLUSIONS:
      Pancreatic cancer likely occurs in case of the inactivation of E-cadherin and
      alpha-catenin genes and abnormal expression of proteins, which significantly
      correlate with tumorigenesis, proliferation, differentiation, and lymph node or
      liver metastasis of pancreatic cancer.

PMID- 14599964
TI  - Islet cell transplantation as a cure for insulin dependent diabetes: current
      improvements in preserving islet cell mass and function.
AB  - OBJECTIVE: To review the current progress of islet cell transplantation in
      patients with insulin-dependent diabetes, emphasizing on the difficulties with
      recovering and preserving islet cell mass and function, 30% of which is lost
      during the peri-transplantation period. RESULTS: The islet-cell isolation
      technique is perfected, but improvements are still progressing in two major
      directions: preservation of islet cells and tolerance induction. Optimum islet
      cell viability and function depends on appropriate revascularization of the islet
      graft and blockade of thrombus formation as well as cytokine and free radical
      release. Conditioning the islet cells in-vitro prior to transplantation to either
      upregulate VEGF expression or downregulate NF-kappa B transcription factor has
      proven to improve revascularization and to prevent islet cell apoptosis and
      cytokine-mediated damage. Tolerance induction is currently being best achieved by
      selecting and combining immunosuppressive agents such as monoclonal antibodies
      which target the major signaling molecules during immune activation, but which
      are least toxic to islet cells. CONCLUSIONS: Patients with insulin-dependent
      diabetes will greatly benefit from current developments in effective approaches
      to protect islets during the peritransplant period. Emerging interest in stem
      cell biology and differentiation may provide the ultimate solution to the problem
      of organ scarcity and islet cell protection from the peritransplant induced
      damage.

PMID- 14599965
TI  - NF-kappa B in allograft rejection.
AB  - Nuclear factor-kappa B (NF-kappa B) as an essential transcription factor in the
      control of expression of the cytokine-induced genes in immune and inflammatory
      responses regulates cytokines in allograft rejection. In this review, we
      summarize the general properties of NF-kappa B and the principal findings to shed
      new light on transplantation.

PMID- 14599966
TI  - Allolymphocyte apoptosis induced by soluble liver specific antigen.
AB  - OBJECTIVE: To investigate the alloimmunogenicity of liver specific antigen and
      its effects on allolymphocytes. METHODS: Liver specific antigen isolated from
      inbred F344 rats was used as immunogen to immunize inbred Lew rats through
      different immunization pathways such as low-dose long-term hind footpad, high
      dose portal vein and thymus immunization. Western blotting, DNA fragments gel
      electrophoresis, mixed lymphocyte culture (MLC) and mixed lymphocyte hepatocyte
      culture (MLHC) were employed to analyze the immune state after immunization.
      RESULTS: At the time point of sampling, different degree of specific low
      immunoresponses appeared in all immunized groups as well as cyclophosphamide (CY)
      treated group. Compared with group I, other groups expressed caspase-3
      significantly as detected by using Western blotting. DNA fragment gel
      electrophoresis of splenocytes showed lymphocyte apoptosis. Compared with the
      group I, MLC of the experimental groups showed no significant changes except that
      of the group V, whereas MLHC decreased markedly (P<0.05). CONCLUSIONS: Liver
      specific antigen not only has alloimmunogenicity to induce alloimmunoreaction but
      induce antigen specific low immunoresponses and antigen specific lymphocyte
      apoptosis by high-dose or low-dose long-term immunization. It may be an important
      transplantation antigen that may lead to a novel way to liver transplantation
      immunotolerance.

PMID- 14599967
TI  - Role of mitogen activated protein kinase cascade pathway and anti-stress response
      in liver transplantation.
AB  - OBJECTIVE: To explore the changes of mitogen activated protein kinase (MAPK)
      cascade pathway and anti-stress response of hepatocytes after liver
      transplantation. METHODS: Ten normal liver specimens and 18 punctured donor liver
      specimens were divided into 3 groups: A (control:10), B (no rejection:10) and C
      (acute rejection:8). MAPK, Ras, Jun and heat shock protein 70 (HSP70) were tested
      immunohistochemically while Ras and HSP70 were tested by in situ hybridization.
      All sections were subjected to image analysis. RESULTS: Protein expressions of
      MAPK, Ras and Jun were increased by an ascending order of groups A, B and C. The
      protein expression of HSP70 was the highest in group B but lower in group C.
      Expressions of Ras and HSP70 mRNA were consistent with those of protein.
      CONCLUSIONS: The changes of the MAPK cascade pathway and anti-stress response of
      hepatocytes after liver transplantation are one of regulation mechanisms for
      protecting the hepatocytes from damage after liver transplantation. This
      mechanism is active to support individual survival

PMID- 14599969
TI  - Cavoportal hemitransposition in liver transplantation: a new technique.
AB  - OBJECTIVE: To introduce a new surgical technique--cavoportal hemitransposition in
      liver transplantation. METHODS: Since Tzakis first reported liver transplantation
      with cavoportal hemitransposition in the presence of diffuse portal vein
      thrombosis in 1998, five relevant research papers have been published, in which a
      total of 23 cases were treated. RESULTS: Of the 23 cases, 11 underwent
      conventionally cavoportal anastomosis as an end-to-end anastomosis, 8 renoportal
      anastomosis, and 4 end-to-side anastomosis preceded by piggyback. Eight patients
      died after operation. Fifteen patients are still alive with normal liver and
      kinase function, with a longest follow-up of 37 months. They enjoy a normal life
      without dietary or other restriction. CONCLUSION: Portal vein thrombosis is no
      longer an absolute contraindication to liver transplantation. This new technique
      is useful and reliable for liver transplantation.

PMID- 14599968
TI  - Dynamic alteration of HBV markers on active HBV replicative recipients after
      liver transplantation: a preliminary report.
AB  - OBJECTIVE: To investigate the dynamic alternations of HBV markers of active HBV
      replication recipients receiving lamivudine prophylaxis after liver
      transplantation. METHODS: Serial liver biopsy samples and sera were obtained from
      15 recipients and examined with enzyme-linked radioimmunoassay for HBsAg, HBeAg,
      HBsAb, HBcAb and HBeAb, and fluorescent quantitative assay for quantitation of
      HBV DNA in serum. Immunohistochemical staining of HBsAg, HBcAg and HBV DNA
      hybridization in situ were used to detect HBV markers in liver biopsy samples.
      RESULTS: 100 mg lamivudine taken orally every day for 2 weeks before
      transplantation enabled 12 (80%) of 15 active viral replication recipients (HBV
      DNA positive) to converse to HBV DNA negative. HBsAb, HBcAb and HBeAb in serum
      emerged in 1-2 weeks after liver transplantation, and disappeared gradually
      within 6 months; HBV DNA fluorescent quantitative assay showed constant
      negativity in serum. Immunohistochemical staining of HBsAg, HBcAg and HBV DNA
      hybridization in situ in liver biopsy samples showed negative results
      synchorously. Eight of the 15 HBV active replication recipients lost HBV markers
      thoroughly both in serology and tissue staining as well as HBV DNA hybridization
      in situ of serial liver biopsy samples from 12 to 44 weeks after liver
      transplantation. Should any of HBsAg, HBeAg in serology and HBsAg, HBcAg in
      immunohistochemical staining was positive, or HBV DNA detectable in serum, or HBV
      DNA hybridization in situ in liver tissue positive, allograft HBV reinfection or
      De novo liver allograft infection could be diagnosed. Furthermore, if associated
      with elevation of ALT and bilirubin, the diagnosis of HBV hepatitis recurrence
      could be established. CONCLUSION: Allograft HBV reinfection or De novo liver
      allograft infection in active viral replication recipients could be prevented
      with lamivudine regimen, and further clearance of HBV may be possible if proper
      measures are taken.

PMID- 14599970
TI  - Modified hepatic outflow tract reconstruction in piggyback liver transplantation.
AB  - OBJECTIVE: To summarize the experience in modified reconstruction of the hepatic
      outflow tract during piggyback liver transplantation at our hospital. METHODS:
      The clinical data on 67 patients undergoing piggyback liver transplantation with
      modified hepatic outflow tract reconstruction from January 1999 to October 2002
      were analyzed retrospectively. RESULTS: In this group, 7 patients (10.45%) died
      perioperatively. Complications included: pulmonary infection (38 patients);
      multiple organ system failure (10), intraperitoneal bleeding (6), acute
      respiratory distress syndrome (14), thrombosis of the hepatic artery (1), and
      bile leakage (1). No hepatic outflow occluded. Two recipients survived for over 3
      years, 8 over 2 years, and 19 over a year. CONCLUSION: Modified hepatic outflow
      reconstruction in piggyback liver transplantation may increase the success rate
      of liver transplantation and decrease technical complications.

PMID- 14599971
TI  - Tamoxifen combined with octreotide or regular chemotherapeutic agents in
      treatment of primary liver cancer: a randomized controlled trial.
AB  - OBJECTIVE: To evaluate the effect of tamoxifen (TAM) combined with a somatostatin
      analogue, octretide (OCT) on advanced liver cancer and whether tamoxifen combined
      with OCT is superior to regular chemotherapeutic agents 5-Fu and mitomycin C
      (MMC). METHODS: Thirty-nine patients with inoperable liver cancer were randomly
      subdivided into TAM+OCT group (n=24) and regular chemotherapeutic group (n=15).
      They received treatment for three months respectively. Blood cell count, liver
      function, immunologic function, blood alpha-FP was regularly measured. Liver lump
      and extrahepatic metastasis were examined by CT. The patients were followed up
      after treatment and conducted survival analysis. RESULTS: In the TAM+OCT group,
      complete response is 4 patients, partial response is 7 patients, no change is 9
      patients and progressive disease is 4 patients; blood level of ALT and AST had no
      noticeable change, IgE and IgG increased (P<0.01), and alpha-FP lowered (P<0.05).
      In regular chemotherapeutic group, no change is 4 patients and progressive
      disease is 11 patients. There was conspicuous statistical difference in the two
      groups. The accumulative survival rates of 6 months, 1 year and 2 years were
      95.7% vs 41.2% (P<0.01), 63.7% vs 21.1% (P<0.01), 25.4% vs 0 (P<0.01),
      respectively. Medium survival time was 12.8 months in TAM+OCT group and 5.5
      months in chemotherapeutic group. CONCLUSIONS: TAM+OCT excerts reliable
      therapeutic effect on patients with inoperable ER(+) hepatocellular cancer. It is
      superior to 5-Fu and MMC in increasing the survival rate, prolonging survival
      time, and reducing side-effects.

PMID- 14599973
TI  - Pylephlebitis and liver abscess mimicking hepatocellular carcinoma.
AB  - OBJECTIVE: To characterize the clinical and radiographic findings in patients
      with pylephlebitis and liver abscess with an emphasis on the findings that help
      to differentiate this disorder from portal vein occlusion associated with
      hepatocellular carcinoma. METHODS: We analyzed the clinical findings and
      radiographic images of four patients with pylephlebitis and liver abscess(es) who
      had been misdiagnosed as having hepatocellular carcinoma with portal vein
      thrombosis. Their medical records were reviewed in terms of clinical
      presentation, physical findings, laboratory data, treatment, and follow up.
      RESULTS: All patients undergoing color duplex ultrasonography had an echogenic
      thrombus within an expanded portal vein with negative color-flow findings within
      the thrombus. Contrast enhanced CT in all the patients demonstrated portal vein
      thrombosis associated with "liver masses". An intra-abdominal site of infection
      responsible for the subsequent ascending infection of the portal vein and liver
      was not identified in any patient on initial CT scan. At presentation, all
      patients were febrile and three of them had an elevated white blood cell count as
      well. All patients showed abnormalities of liver function. CONCLUSIONS: Liver
      abscess(es) associated with pylephlebitis may mimic hepatocellular carcinoma with
      portal vein thrombosis. Clinical features that help to distinguish the two
      entities include presence or absence of fever, elevated white blood cell count,
      elevated alpha-fetoprotein, cirrhosis, and risk factors for hepatocellular
      carcinoma.

PMID- 14599972
TI  - Preoperative selective portal vein embolization in two-step hepatectomy for
      hepatocellular carcinoma in injured livers: a preliminary report.
AB  - OBJECTIVE: To study the effect of preoperative selective portal vein embolization
      (SPVE) in the two-step hepatectomy for patients with primary hepatocellular
      carcinoma (HCC) in injured livers. METHODS: Twenty-six patients with HCC and
      cirrhosis who were not suitable for curative hepatectomy were treated by
      ultrasound-guided percutaneous transhepatic SPVE with a fine needle. The success
      rate, side-effects and complications of SPVE, serial changes of hepatic lobe
      volume and rate of two-step curative hepatectomy after SPVE were observed.
      RESULTS: SPVE was performed in 24 patients (92.3%). In patients whose right
      portal vein branches were embolized, the right hepatic volume decreased but the
      left hepatic volume increased gradually. The ratio of the right hepatic volume to
      the total hepatic volume decreased from 64.0% before SPVE to 60.8% after l week,
      55.1% after 2 weeks and 52.7% after 3 weeks, respectively. The side-effects
      included different degree of pain in the liver quandrant (17 patients), lower
      fever (9), and nausea and vomiting (7). The levels of aspartate alanine
      transaminase (AST), alanine transaminase (ALT) and total bilirubin (TBIL)
      increased after SPVE, but returned to the preoperative levels in 1 week. After 2
      4 weeks, two-step curative hepatectomy for HCC was performed in 13 patients
      (54.2%). CONCLUSIONS: Ultrasound-guided percutaneous transhepatic SPVE with a
      fine needle is feasible and safe. It can extend the indications of curative
      hepatectomy for HCC in injured livers, and increase the safety of two-step
      hepatectomy.

PMID- 14599974
TI  - Portal hypertensive gastropathy and its interrelated factors.
AB  - OBJECTIVE: To investigate the influences of helicobacter pylori (Hp) infection,
      liver function, gastroesophageal varicosity, esophageal varicosity ligation
      (EVL), and esophageal varicosity sclerotherapy (EVS) on patients with portal
      hypertensive gastropathy (PHG). METHODS: Fourty-seven patients with liver
      cirrhosis included 34 patients with PHG and 13 patients without PHG. Liver
      function, Hp infection, and gastroesophageal varicosity were investigated
      clinically in all patients, and gastroscopy was made again in patients with EVL 1
      2 months after operation to observe the changes of PHG. RESULTS: The rate of Hp
      infection was lower in patients with liver cirrhosis than in controls. There was
      no relationship between Hp infection and PHG. The patients with gastroesophageal
      varicosity had a high incidence of PHG. CONCLUSIONS: Despite no relationship
      between Hp infection and PHG, liver dysfunction can affect and promote PHG.
      Gastroesophageal varicosity may be closely related to PHG, but their degrees are
      not related. PHG can be caused or promoted by EVL.

PMID- 14599975
TI  - Influence of HLA class II molecules on the outcome of hepatitis B virus infection
      in population of Zhejiang Province in China.
AB  - OBJECTIVE: To investigate the correlation between HLA class II molecules and the
      different outcome of viral hepatitis B. METHODS: Thirty patients with chronic
      hepatitis B and 56 subjects who had spontaneously recovered from HBV infection in
      Zhejiang were enrolled in this investigation. HLA class II molecules types and
      alleles were determined by PCR-ssp. RESULTS: HLA-DR12 was found in 21 of the 56
      subjects (38%) recovered from hepatitis B, compared to 3 of the 30 patients with
      chronic hepatitis B [10%, relative risk (rr), 0.19; Pcorr<0.025]. The frequency
      of the allele of HLA-DR12 DRB1*1201 was higher in the subjects recovered from
      hepatitis B infection (32%) than in the patients with chronic hepatitis B (3%;
      rr, 0.07; Pcorr<0.005). On the contrary, more HLA-DR9 was detected in the
      patients with chronic hepatitis B (43%) than in the subjects who recovered from
      hepatitis B infection (18%; rr, 3.52; Pcorr<0.025). HLA-DQ9 was also detected
      with a higher frequency in the patients with chronic hepatitis B (43%) than in
      the subjects who recovered from hepatitis B (20%; rr, 3.13; Pcorr<0.05).
      CONCLUSIONS: The HLA class II molecule DR12 and its allele DRB1*1201 are
      associated with protection against chronic hepatitis B in Zhejiang Province,
      China. HLA-DR9 and DQ9 are associated with chronicity of HBV infection.

PMID- 14599976
TI  - Hepatitis gene chip in detecting HBV DNA, HCV RNA in serum and liver tissue
      samples of hepatitis patients.
AB  - OBJECTIVE: To study the preparation of diagnostic gene chip for detecting
      hepatitis B virus (HBV) and hepatitis C virus (HCV) and its accuracy in detecting
      HBV DNA and HCV RNA in serum and liver tissues. METHODS: The probes, which depend
      on the conservative gene fragment of hepatitis virus, was designed, synthesized
      and spotted on the modified glass. The probes and some other control probes were
      assembled on the diagnostic microarray of hepatitis virus. The gene of hepatitis
      virus, purified from blood or tissue, was labeled with fluorescence and
      hybridized to the microarray. The hybridized microarry was scanned with
      microarray scanner and the diagnostic result was analyzed from the scanning data.
      Fourty patients with hepatitis B virus and 40 healthy people or 40 patients with
      hepatitis C virus were subjected to detection of HBV DNA and HCV RNA with the
      hepatitis virus gene chip by the double-blind method. Paraffin liver specimens
      obtained from 99 cases of posthepatitic cirrhosis were used to detect HBV DNA.
      The liver tissues and serum from 15 cases of chronic hepatitis B were used to
      detect HBV DNA. Simultaneously, HBsAg and HBcAg were detected in the serum by
      fluorescence microparticle quantitation, HBV DNA and HCV RNA in the serum by PCR,
      and HBcAg in liver tissues by immunocytochemistry or HBV DNA by in situ molecular
      hybridization. RESULTS: Chip detection of serum specimens showed that 30 patients
      were HBV DNA positive and 10 HBV DNA negative in the 40 patients with HBV
      positive, 25 patients were HCV RNA positive and 15 patients were HCV RNA negative
      in the 40 patients with HCV positive, and all were HBV and HCV negative in the 40
      healthy people. In 15 patients with HBV marker positive who were subjected to
      liver biopsy, 15 patients were detected HBV DNA positive in serum by gene chip,
      15 patients HBcAg positive in liver tissues by immunocytochemistry, 14 patients
      HBV DNA positive in liver tissues by in situ molecular hybridization, and 14
      patients HBV DNA positive in liver tissues by gene chip. Paraffin liver tissues
      specimens from the 99 patients with posthepatitis B cirrhosis showed that 67
      patients were detected HBcAg positive by immunocytochemistry, 53 patients HBV DNA
      positive by in situ molecular hybridization, and 46 patients HBV DNA positive by
      gene chip. In the 46 patients, 40 patients were detected HBV DNA and HBcAg
      positive by in situ molecular hybridization and immunocytochemistry, 6 patients
      only HBcAg positive, and 33 patients HBcAg negative. CONCLUSIONS: The designed
      diagnostic gene chip can be used to simultaneously detect serum HBV DNA and HCV
      RNA, but the positive rate of HCV RNA diagnosed by this chip is lower. The gene
      chip can detect HBV DNA in serum and in liver tissue.

PMID- 14599977
TI  - Effect of spleen on immune function of rats with liver cancer complicated by
      liver cirrhosis.
AB  - OBJECTIVE: To establish a rat model of liver cancer complicated by liver
      cirrhosis and explore the effects of the spleen on immune function in this model.
      METHODS: Liver cirrhosis was inflicted in rats by percutaneous injection of 40%
      CCl4 on the back. Walker-256 tumor cells were inoculated in the cirrhotic liver
      and splenectomy was performed. Two weeks later, the growth and metastasis of
      tumor were observed and the amount of ascites and the activity of NK cells and
      CD25 cells were investigated. RESULTS: The amount of ascites and tumor volume
      were significantly higher in splenectomy group than in controls (P<0.01). Two
      weeks after inoculation, the activity of NK cells in both groups was decreased as
      compared with that before the inoculation (P<0.01). There was no significant
      difference between the two groups before and after the inoculation (P>0.05). The
      number of CD25 in both groups was higher than that before the inoculation
      (P<0.01). However, there was no significant difference between the two groups
      before and after the inoculation (P>0.05). CONCLUSIONS: Splenectomy in early
      stage of tumor inoculation can stimulate the tumor growth and metastasis. The
      activity of NK cells and the number of CD25 are inhibited by tumor itself, not by
      splenectomy.

PMID- 14599978
TI  - Transcriptional activation function of hepatitis B virus Pre S1 protein in yeast.
AB  - OBJECTIVE: To explore the feasibility of cloning of the hepatocyte receptor
      interacting with the Pre S1 protein of HBV by two-hybrid system. METHODS: Yeast
      expression plasmids encoding fusion proteins of full length or portions of Pre S1
      of HBV and DNA binding domain of yeast protein GAL4 were constructed and used to
      transform yeast reporter strain SFY526. Reporter gene product beta-galactosidase
      activity was assayed as a measure of transcriptional activation in yeast.
      Mammalian expression plasmid encoding fusion proteins of full length Pre S1 and
      DNA binding domain of GAL4 was constructed and used to cotransfect hepatoma cell
      line Huh-7 together with CAT reporter plasmid. Cell extracts were assayed for CAT
      activity by thin-layer chromatography. RESULTS: The fusion proteins of full
      length Pre S1 protein and GAL4 DNA binding domain presented transcriptional
      activation function in yeast. The transcription activating sequence was localized
      to the 21 to 47 amino acids of Pre S1 protein. Fusion proteins of full length Pre
      S1 and GAL4 DNA binding domain did not show transcriptional activation function
      in mammalian cells. CONCLUSIONS: The transcription activating sequence of HBV Pre
      S1 protein in yeast overlaps the hepatocyte receptor binding site. The
      transcriptional activation function of HBV Pre S1 protein in yeast may prevent
      researchers from using yeast two-hybrid system to clone HBV receptor interacting
      with Pre S1 protein. However, the Pre S1 protein does not show transcriptional
      activation function in mammalian cells. Mammalian two-hybrid system may be a
      practical method to clone the HBV hepatocyte receptor interacting with Pre S1
      protein.

PMID- 14599979
TI  - Expression and role of inducible nitric oxide synthase in ischemia-reperfusion
      liver in rats.
AB  - OBJECTIVE: To investigate the expression and the role of iNOS expression in
      hepatic ischemia-reperfusion (I/R) injury. METHODS: Male Wistar rats were
      subjected to 30-minute hepatic ischemia, then iNOS protein and iNOS mRNA
      expression in liver tissue was assessed by Western blot and RT-PCR analysis
      respectively at different time points after reperfusion. The effects of L-NAME
      (Nomega-nitro-L-arginine methyl ester, a nonselective NOS inhibitor) or AE-ITU
      (aminoethytl-isothiourea, a relative selective inhibitor of iNOS) treatment were
      also evaluated. RESULTS: High levels of iNOS protein and mRNA expression were
      detected in the liver tissue subjected to I/R, but not in the sham-operated rats.
      iNOS protein and iNOS mRNA expression reached a maximum on the first day after
      reperfusion and decreased later. The levels of iNOS protein and iNOS mRNA
      disappeared on 7th, 3rd day after reperfusion respectively. The high iNOS
      expression was correlated with hepatic dysfunction. L-NAME administration
      worsened hepatic dysfunction induced by hepatic I/R. In contrast, AE-ITU 
      administration showed mild protective effects against hepatic dysfunction induced
      by hepatic I/R. CONCLUSION: Ischemia-reperfusion may induce or up-regulate the
      expression of iNOS protein and iNOS mRNA, which is detrimental to hepatic I/R
      injury

PMID- 14599980
TI  - Evaluation on expression of the recombinant S gene of human hepatitis B virus in
      vitro and in vivo.
AB  - OBJECTIVES: To construct a DNA vaccine capable of expressing the S gene of
      hepatitis B virus (HBV) and evaluate the expression of the recombinant S gene in
      vitro and in vivo. METHODS: A cloned S-X gene fragment was inserted into an
      eukaryote expression vector to construct a recombinant expressing plasmid pCMV
      SX. The recombinant plasmid was transcribed in vitro with a T7 promoter
      transcription system and transfected into a human hepatoblastoma cell line HepG2.
      The expression of the S gene was detected by Northern blot hybridization, Western
      blot hybridization, and enzyme-linked immunosorbent assay (ELISA), respectively.
      BALB/c mice were inoculated with the recombinant plasmid, and the efficiency of
      DNA-based immunization in eliciting anti-HBs was evaluated by ELISA. RESULTS: In
      vitro transcription of the subcloned HBV S gene was confirmed by Northern blot
      hybridization. The results of Western blot hybridization and ELISA showed that
      the S gene was expressed exactly in HepG2. In immune experiment, 2 of 10
      immunized mice were shown to induce antibody against HBsAg. CONCLUSION: The
      recombination and expression of the S gene can be achieved successfully in vitro.
      And the recombinant plasmid is able to elicit humoral immune response in mice.

PMID- 14599981
TI  - The effect of lipopolysaccharides on the expression of CD14 and TLR4 in rat
      Kupffer cells.
AB  - OBJECTIVE: To assess the effect of lipopolysaccharides (LPS) on the expression of
      CD14 and TLR4 in rat Kupffer cells (KCs). METHODS: In rat KCs induced by LPS, the
      changes of CD14 and TLR4 expression were measured by RT-PCR and
      immunohistochemistry, and the expressions of TNF-alphamRNA, IL-6mRNA or the
      concentrations of TNF-alpha, IL-6 were estimated by in situ hybridization,
      radioimmunoassay, and others. RESULTS: The expressions of CD14 and TLR4 in KCs
      induced by LPS were markedly increased in a dose-dependent manner (10 mg/L-1
      microg/L) or in a time-dependent manner (0.5 h-24 h), with the peaked expression
      of CD14 at 3-6 hours. The expressions of CD14 and TLR4 in KCs stimulated by the
      active mediators from KCs which had been exposed to LPS for 1 hour were obviously
      increased. CONCLUSIONS: There is a close relationship between LPS or the active
      mediators from KCs induced by LPS and the expressions of CD14, TLR4. It is
      implied that the increase of TLR4, CD14 expression may be induced by LPS within 1
      3 hours, and further increase of TLR4, CD14 expression may be correlated with the
      cytokines produced by KCs.

PMID- 14599982
TI  - Detection of distribution of copper inside and outside of lysosomes in cultured
      hepatolenticular degeneration fibroblasts by electron probe X-ray microanalysis.
AB  - OBJECTIVE: To observe the distribution of copper in the subcellular structure for
      the understanding of primary pathogenesis of hepatolenticular degeneration (HLD).
      METHODS: Skin fibroblasts taken from HLD patients were cultured as an in vitro
      model of HLD, and the control cells taken from healthy volunteers were cultured
      in the same way. The distribution of copper inside and outside of lysosomes in
      fibroblasts was detected by quantitative electron probe X-ray microanalysis. The
      relationship between the subcellular location of copper and the genotype of the
      patients, and relationship between the distribution of copper and the course of
      the disease were analyzed. RESULTS: The content of Cu2+inside lysosomes of HLD
      cells (14.6+/-2.1 mmol/kg) and of heterozygote cells (11.6+/-0.6 mmol/kg) was
      higher than that of normal cells (4.5+/-1.2 mmol/kg) (P<0.01). The content of
      Cu2+outside lysosomes of HLD cells (17.5+/-4.2 mmol/kg) and of heterozygote cells
      (12.0+/-0.9 mmol/kg) was higher than that of normal cells (4.7+/-1.2 mmol/kg)
      (P<0.01). The distribution of copper in the subcellular structure was correlated
      with disease courses of HLD patients. With the progression of the disease, more
      copper was deposited in lysosomes (r=0.85, P<0.01). The content of copper in the
      diffused cytoplasmic compartment in HLD cells was correlated with that of sulfur
      (r=0.86, P<0.05), but not in heterozygote and normal cells. CONCLUSIONS: In the
      early stage of HLD, copper is accumulated outside lysosome, which is paralleled
      with increase of metallothionein-like proteins (copper and sulfur-binding
      proteins). With the development of the disease, more copper is deposited inside
      lysosome than outside lysosome. We conclude that the up-regulation expression of
      copper and sulfur-binding proteins and copper accumulation in lysosomes may play
      an important role in lowering the ATP7B gene mutation-induced toxic effects of
      free copper on the cell.

PMID- 14599983
TI  - Expression of AFPmRNA in blood of patients with recurrent hepatocellular
      carcinoma.
AB  - OBJECTIVES: To detect the expression of human alpha-fetoprotein mRNA (AFPmRNA) in
      peripheral blood (PBL) of recurrent hepatocellular carcinoma (HCC) by using
      nested reverse transcriptase polymerase chain reaction (nested RT-PCR) and to
      discuss relations between AFPmRNA and recurrent HCC. METHODS: Five ml peripheral
      blood samples were obtained from 19 patients with recurrent HCC. To identify HCC
      cells in PBL, liver-specific AFPmRNA was amplified from the total RNA extracted
      from the whole blood by nested RT-PCR. RESULTS: Seven patients (36.8%) with
      recurrent HCC were detected AFPmRNA, and 12 patients with recurrent HCC were
      AFPmRNA negative (63.2%). There was no significant relation between patients with
      AFPmRNA positive and AFPmRNA negative (P>0.05) in judging the origin of recurrent
      HCC. CONCLUSION: AFPmRNA may not be used as a marker of origin of recurrent HCC.

PMID- 14599984
TI  - Establishment of hepatocarcinoma cell line transfected by the B7 gene and its
      biocharacteristics.
AB  - OBJECTIVE: To study the function of costimulation sign in tumor immunology and
      construct the new cell line B7+ Smmc7721. METHODS: The B7 gene was transfected
      into the hepatocarcinoma cell Smmc7721 by liposma. Polymerase chain reaction
      (PCR) and reverse transcriptase-PCR (RT-PCR) were applied to test the result. MTT
      colorimetric assay was used to value the killing effect of lymphokine activated
      killer cells (LAK) activated by IL-2 on the transfected cell line and the
      original line. RESULT: B7+ Smmc7721 was improved to be steadily expressed B7
      molecule and LAK cells could more effectively act on the B7+ Smmc7721 cells.
      CONCLUSION: The B7 gene can be transfected to hepatocarcinoma cells and can be
      expressed steadily in vitro, thus increasing the efficiency of LAK cells
      activated by IL-2 on them.

PMID- 14599985
TI  - Clinical epidemiological study on intrahepatic cholelithiasis: analysis of 8585
      cases.
AB  - OBJECTIVE: To investigate the clinical epidemiology of intrahepatic
      cholelithiasis in Guangxi area, China. METHODS: 8585 cases of cholelithiasis
      proved by surgery in a period of 19 years were analyzed retrospectively. Data
      were collected and analyzed by computer software package PEMS. RESULTS: Cases of
      intrahepatic cholelithiasis accounted for more than one third of cases of
      cholelithiasis treated in the same period. The prevalence of intrahepatic
      cholelithiasis in farmers increased from 23.4% out of all cases with gallstone in
      1981-1985 to 55.8% in 1991-1999. The constituent ratio of intrahepatic
      cholelithiasis in males was nearly the same in females. The peak prevalence age
      of patients with intrahepatic cholelithiasis ranged from 31 to 40 years, and the
      mortality was the highest among all bile stone cases. CONCLUSION: Intrahepatic
      cholelithiasis is by no means a vanishing disease, especially in rural area.

PMID- 14599986
TI  - Pathogenesis of cholangiocarcinoma in the porta hepatis and infection of
      hepatitis virus.
AB  - OBJECTIVE: To study the correlation between human cholangiocarcinoma in the porta
      hepatis and the infection of hepatitis virus. METHODS: Immunohistochemistry was
      used to detect HBxAg and HCV-C protein in formalin-fixed and paraffin-embedded
      samples taken from 68 patients with cholangiocarcinoma in the porta hepatis. The
      findings were reviewed against the clinical records of the patients. RESULTS: Six
      patients (8.8%) were positive for HBxAg and 24 (35%) for HCV-C protein,
      respectively. One patient was positive for both HBxAg and HCV-C protein. There
      were statistically differences in the extent of differentiation, invasion, lymph
      node metastasis, and treatment between the patients with cholangiocarcinomas in
      the porta hepatis with HB(C)V infection and those without infection. CONCLUSIONS:
      HB(C)V infection is correlated to the development of cholangiocarcinoma in the
      porta hepatis. The tumor with HB(C)V infection may have a higher malignancy
      biologically and poorer prognosis. HBxAg and HCV-C protein may play an important
      role in the pathogenesis of cholangiocarcinoma in the porta hepatis.

PMID- 14599987
TI  - Development of an enzyme immune assay for detecting M2 autoantibodies specific
      for primary biliary cirrhosis.
AB  - OBJECTIVE: To develope a new enzyme immune assay (ELISA) for detection of M2
      antibody specific for primary biliary cirrhosis (PBC) by using a triple hybrid
      clone as antigen, which coexpresses the three immunodominant lipoyl domains of
      PDC-E2, BCOADC-E2 and OGDC-E2 from human sources. METHODS: After expressing
      autoantigens of PBC in prokaryote by constructing recombinant expressive plasmid
      successfully, the fusion protein was purified by affinity chromatography. The
      sera of 17 PBC patients were examined. As controls, the sera of 167 non-PBC
      patients and the sera of 1225 normal controls aged under 28 were examined.
      RESULTS: None of the sera from the non-PBC patients or the normal controls was
      positive for anti-M2 shown by the new ELISA. However, the positivity rate for
      anti-M2 in the PBC patients was 100% (17/17), as shown by the new ELISA.
      CONCLUSION: The detection system with a good sensitivity and specificity may be
      used as a powerful method for the diagnosis of PBC.

PMID- 14599988
TI  - Microstructural and ultrastructural changes in the healing process of bile duct
      trauma.
AB  - OBJECTIVE: To explore the mechanism of benign biliary stricture caused by bile
      duct trauma. METHODS: A model of trauma of the common bile duct was established
      in 28 dogs and then repaired. The anastomotic tissues were taken on 3 days, 1
      week, 3 weeks, 3 months, and 6 months respectively after operation and examined
      by using light microscopy and electromicroscopy. Macrophage, transforming growth
      factor beta 1 (TGF-beta1) and alpha-smooth muscle actin (alpha-SMA) were studied
      immunohistochemically. RESULTS: The mucosal epithelium of the common bile duct
      restored poorly, chronic inflammation lasted for a long time, fibroblasts
      proliferated actively, extracellular matrix overdeposited, and myofibroblasts
      functioned actively during the whole healing process. Immunohistochemical test
      showed a high expression of macrophage, TGF-beta1 and alpha-SMA during the
      healing process lasting a long duration. Macrophages were found in the lamina
      propria under mucosa, TGF-beta1 in the granular tissue, fibroblasts and
      endothelial cells of blood vessels, while alpha-SMA in the myofibroblasts and
      smooth muscle tissue. CONCLUSIONS: The healing of the bile duct is in the mode of
      overhealing. Myofibroblast is the main cause for contracture of scar and
      stricture of the bile duct. The high expression of macrophage, TGF-beta1 and
      alpha-SMA is closely related to active proliferation of fibroblasts,
      extracellular matrix overdeposition and scar contracture of the bile duct.

PMID- 14599990
TI  - Analysis and prevention of factors predisposing to infections associated with
      severe acute pancreatitis.
AB  - OBJECTIVE: To analyze factors predisposing to the infections associated with
      severe acute pancreatitis (SAP) and work out ways for their prevention. METHODS:
      208 patients with SAP treated at our hospital from January 1986 to December 2001
      were retrospectively analyzed. RESULTS: Statistical difference in the incidence
      of the infections was found between the following pairs: the groups of bloody or
      non-bloody ascites, paralytic ileus lasting shorter or longer than 5 days,
      Ranson's scores lower or higher than 5, hematocrit lower or higher than 45%, CT
      Balthazar scores lower or higher than 7, and between January 1986-June 1992 or
      July 1992-December 2001 admissions (chi2>7.58, P<0.05), while no statistical
      difference established between the groups of biliogenic and non-biliogenic
      pancreatitis, serum amylase <200 U/L and >/=200 U/L, serum calcium <2 mmol/L and
      >/=2 mmol/L or groups of total parenteral nutrition shorter or longer than 7 days
      (chi2<1.61, P>0.05). CONCLUSIONS: Occurrence of infection in patients with SAP is
      closely related with bloody ascites, paralytic ileus (>/=5 days), Ranson's scores
      (>/=5), hematocrit (>/=45%) and CT Balthazar scores (>/=7), but not with
      pathogenesis, serum calium or total parenteral nutrition. Comprehensive
      prevention of pancreatic infection and individualized therapy may reduce the
      incidence of infection.

PMID- 14599989
TI  - Interventional therapy of malignant obstructive jaundice.
AB  - OBJECTIVE: To assess the short-term results of interventional therapy for
      malignant obstructive jaundice. METHODS: In 82 patients with malignant
      obstructive jaundice, hepatocellular carcinoma was detected in 10 patients,
      carcinoma of gallbladder in 14, hilar biliary carcinoma in 22, pancreatic
      carcinoma in 20, and hilar metastatic carcinoma in 16. Percutaneous transhepatic
      biliary internal and/or external drainage (PTBIED) was performed in 61 patients
      and percutaneous transhepatic insertion of biliary stent (PTIBS) in 21. RESULTS:
      The level of total serum bilirubin (TSB) was reduced in 71 patients and less
      markedly in others. The level of TSB of the 61 patients was reduced from 450.12+/
      113.51 micromol/L before operation to 240.25+/-107.81 micromol/L and 90.91+/
      101.72 micromol/L 1 and 2 weeks after operation respectively. The TSB level of
      the 21 patients was reduced from 410.53+/-98.13 micromol/L to 270.23+/-115.64
      micromol/L and 105.43+/-97.85 micromol/L 1 and 2 weeks after operation,
      respectively. No significant difference was found in the effect between PTBIED
      and PTIBS. Short-term complications developed in 33 patients. Seven patients died
      30 days after operation. CONCLUSION: Interventional therapy may be simple, safe
      and effective in the treatment of malignant obstructive jaundice.

PMID- 14599991
TI  - The effect of FasL gene transfer to islet cells on pancreatic islet allografts.
AB  - OBJECTIVE: To investigate the effect of FasL gene transfer to islet cells on
      pancreatic islet allografts. METHODS: A recombinant and replication-deficient
      type-5 adenovirus encoding murine FasL (AdV- FasL) was constructed by the method
      of calcium phosphate precipitation. Pancreatic islets were infected with the
      recombinant adenovirus AdV-FasL, and transplanted into diabetic recipients. FasL
      expression was detected by RT-PCR and immunohistochemistry. The survival of
      allografts and the apoptosis of gene transferred islet allografts were analyzed.
      RESULTS: All animals receiving islet allograft alone returned to a diabetic state
      by several days (mean survival time 6.3+/-0.6 days). Compared with the control
      group, no delayed rejection and prolonged survival of allografts were observed in
      the group of FasL gene transfer. The rejection was accelerated and the allograft
      survival was shortened to 3.4+/-0.2 days (P<0.05). Pancreatic islets infected
      with AdV- FasL demonstrated positive staining of FasL at 24 h, with an increased
      intensity at 48 h, but not in AdV-5 infected or uninfected islets. TUNEL labeling
      of pancreatic islet allografts at 24, 48 h revealed apoptosis that was not in AdV
      5 infected allografts. CONCLUSIONS: Though co-transplantation of FasL-expressing
      testicular cells can induce privilege of islet allografts and prolong allograft
      survival, direct expression of FasL on islet allografts infected with AdV-FasL
      may accelerate islets rejection by islet apoptosis and granulocyte infiltration.

PMID- 14599992
TI  - Detection of K-ras gene mutation at codon 12 by pancreatic duct brushing for
      pancreatic cancer.
AB  - OBJECTIVE: To assess the diagnostic value of endoscopic pancreatic duct brushing
      in detecting mutation of the K-ras gene at codon 12 in cytologic specimens from
      patients with pancreatic cancer. METHODS: Thirty-five patients treated at
      Changhai Hospital, Shanghai between 1999 and 2001 were enrolled. Their cells
      obtained by pancreatic duct brushing during endoscopic retrograde
      cholangiopancreatography (ERCP) were suspended with phosphate buffer solution
      (PBS). DNA of the cells was extracted and mutation of the K-ras gene at codon 12
      detected by means of PCR-SSCP. RESULTS: The K-ras gene mutation rate of
      pancreatic cancer was 70%, which was higher than that of chronic pancreatitis
      (14%, P<0.05). K-ras gene mutation was not found in patients with pancreatic
      cystocarcinoma and duodenum carcinoma. As to the location of pancreatic cancer,
      no significant difference was observed between the head, the body and tail. The
      sensitivity, specificity, accuracy of pancreatic duct brushing in detecting
      pancreatic cancer was 70%, 94%, and 83%, respectively. CONCLUSION: K-ras analysis
      of pancreatic brushing samples is helpful in the diagnosis of patients with early
      pancreatic cancer.

PMID- 14599993
TI  - Chronic bronchitis: an old man's enemy?

PMID- 14599994
TI  - Diagnosis and management of heart failure: implications of the recent European
      Society of Cardiology Guidelines for the older patient.

PMID- 14599995
TI  - Living and dying with congestive heart failure: addressing the needs of older
      congestive heart failure patients.

PMID- 14599996
TI  - Primary hyperparathyroidism in the older person.
AB  - Primary hyperparathyroidism (PHPT) is a common condition which may have few
      symptoms. One of the principal concerns in the older person with minimally
      symptomatic PHPT is restoration of bone mineral density and prevention of
      fracture. Other important considerations are cardiovascular risk and quality of
      life. Surgery, the traditional treatment of choice, may not always correct these
      factors. We present a review of the literature and advice of medical therapies
      which should be of benefit, with emphasis on a multifaceted approach in
      protecting the patient from PHPT.

PMID- 14599997
TI  - Onset of mobility disability among community-dwelling old men and women. The role
      of tiredness in daily activities.
AB  - BACKGROUND: in the primary prevention of disability among older adults it might
      be useful to identify individuals at high risk for functional decline before it
      occurs. OBJECTIVE: to examine whether tiredness in daily activities is an
      independent determinant of onset of mobility disability at 1 1/2-year follow-up
      among non-disabled older men and women. DESIGN: a prospective study with 1 1/2
      year follow-up. SETTING: 34 communities in four counties in Denmark. SUBJECTS:
      1396 older non-disabled adults (74-75 and 80 years old) living in 17 of the
      participating communities. METHODS: questionnaire surveys at baseline and at 1
      1/2-year follow-up. Tiredness in daily activities was measured by questions about
      tiredness in six mobility activities. Onset of mobility disability was measured
      as onset of need for help in one to six mobility activities. RESULTS: men and
      women who felt tired in their daily activities at baseline had a higher risk of
      onset of mobility disability at 1 1/2-year follow-up, when adjusted by the
      covariates. In addition, low social participation, poor psychological function,
      and physical inactivity were independent risk factors of onset of mobility
      disability among men, and home help, low sense of coherence and physical
      inactivity were independent risk factors of onset of mobility disability among
      women. CONCLUSION: older people who complain about tiredness are at higher risk
      of becoming disabled than others. This highlights the need for alertness and
      management of this early sign of functional decline in a preventive perspective.

PMID- 14599998
TI  - Effects of a 5-year exercise-centered health-promoting programme on mortality and
      ADL impairment in the elderly.
AB  - OBJECTIVE: the effects of regular exercise over 5 years on mortality and ADL
      impairment were evaluated in elderly people. DESIGN: intervention study. SETTING:
      Tsuru City, Yamanashi Prefecture, Japan. METHODS: the subjects of this study were
      245 elderly people living at home. Of these individuals, 155 (56 males aged
      76.5+/-4.2 years at the baseline level; 99 females aged 76.2+/-4.8 years) who
      voluntarily participated in our original health-promoting programme were regarded
      as an intervention group. The remaining 90 (29 males aged 77.6+/-5.2 years at the
      baseline level; 61 females aged 77.3+/-5.1 years) were regarded as a control
      group. The programme was a 5-year intervention consisting of collective sessions
      given six times a year every 2 months. The intervention was a combination of an
      exercise programme based on theories of exercise physiology and a support
      programme based on health education theories. The relative risks of death and ADL
      impairment adjusted for age, presence or absence of cardiovascular or musculo
      skeletal disorders, and functional fitness level at the baseline were calculated
      using logistic regression analysis. RESULTS: the rates of participant compliance
      per year were 67.7% in the first year of the intervention period and gradually
      decreased thereafter to 43.9% in the last year. Amongst female subjects the
      percentage of those who exercised habitually at the end of the study period was
      the same as that in the baseline in the intervention group but was significantly
      lower at the end of the study in the control group (chi2 = 10.576, P < 0.01). The
      relative risk of death in the intervention group was 1.0 (95% CI 0.22-4.51)
      amongst the males and 0.16 (95% CI 0.03-0.81) amongst the females. Relative risk
      of ADL impairment was 0.22 (95% CI 0.03-1.42) amongst the males and 0.36 (95% CI
      0.13-1.02) amongst the females. CONCLUSION: These findings suggest that the
      improved mortality and state of independence in the female portion of the
      intervention group occurred as a result of increased physical exercise levels in
      daily life. However, validation of our results must await research that employs a
      randomized control trial to avoid various biases and confounding factors between
      the intervention and the control groups.

PMID- 14599999
TI  - Suitability of the WHOQOL-BREF for community-dwelling older people in Taiwan.
AB  - BACKGROUND: while life expectancy among older people has been lengthened due to
      improved public health and medical interventions, the importance of health
      related quality of life in later life has also increased. However, the
      application of a generic health-related quality of life measure for older people
      needs to be carefully validated. OBJECTIVE: to evaluate the practicality,
      reliability, validity, and responsiveness of the use of the brief version of the
      World Health Organization Quality of Life for people aged 65 years or older.
      DESIGN: a prospective study. METHODS: for a baseline assessment, 1200 community
      dwelling older people living in Shin-Sher Township of Taichung County, Taiwan,
      completed the brief version of World Health Organization Quality of Life at their
      residences either by themselves or with the assistance of an interviewer.
      Furthermore, score changes in each health-related quality of life domain after a
      fall were followed up for assessing its responsiveness. RESULTS: the average
      length of time required to complete the questionnaire was short (10.6 minutes for
      self-administration and 15.3 minutes for personal interview), and the score
      distribution in each domain was symmetrical with no floor or ceiling effect.
      Furthermore, all domain scores indicated excellent discriminant validity,
      construct validity, and responsiveness as well as good internal consistency and
      intra- and inter-observer test-retest reliabilities. Nevertheless, two items
      related to work capacity and sexual activity had higher missing values (4.5% and
      16.5%) and poor interobserver test-retest reliabilities (0.43 and 0.20).
      Suggested modifications to the two items for older people are discussed.
      CONCLUSION: with a few modifications, the brief World Health Organization Quality
      of Life is a suitable health-related quality of life instrument for older people.

PMID- 14600000
TI  - Pulmonary embolism: differences in presentation between older and younger
      patients.
AB  - BACKGROUND: the incidence of pulmonary embolism increases with age but the
      'classical' presentation of acute pulmonary embolism may not occur in older
      persons. OBJECTIVES: to compare the clinical presentation of younger and older
      patients with acute pulmonary embolism. DESIGN: retrospective identification of
      60 consecutive cases of spiral computed tomography confirmed acute pulmonary
      embolism over a 3-year period, with blinded review of radiological films and
      electrocardiographs, and analysis of clinical presentation. SETTING: a district
      general hospital serving a population of 200,000 people. SUBJECTS: 31 younger and
      29 older patients with acute pulmonary embolism. RESULTS: older persons less
      often complained of pleuritic chest pain (P < 0.02), particularly as their
      primary presenting complaint (P < 0.002). Twenty-four percent of older but just
      3% of younger persons presented with collapse (P < 0.02), despite similar
      proportions of central and peripheral emboli in the two groups. Older persons
      were more often cyanosed (P = 0.05) and hypoxic (P < 0.04) than younger persons
      but there were no significant differences with respect to heart rate, respiratory
      rate or mean arterial blood pressure. CONCLUSIONS: older people present
      atypically with acute pulmonary embolism, potentially leading to delays in
      diagnosis and initiation of treatment. Collapse is a particularly important
      symptom of acute pulmonary embolism in older persons, even in the absence of
      pain.

PMID- 14600001
TI  - Diagnosing cognitive impairment and dementia in primary health care -- a more
      active approach is needed.
AB  - OBJECTIVE: to determine the documentation rate of dementia in primary health
      care, the clinical characteristics of patients with documented and undocumented
      dementia, and the diagnostic evaluations made in cognitive impairment. DESIGN:
      cross-sectional population-based study with a retrospective review of medical
      history. SETTING: primary health care in the municipality of Lieto, Southwestern
      Finland. SUBJECTS: all the inhabitants aged 64 and over in Lieto. Participation
      rate 82%, numbers = 1260. MEASUREMENTS: assessment of dementia according to DSM
      IV criteria, and severity according to Clinical Dementia Rating. Possible
      documentation of dementia and evaluations done were reviewed from primary health
      care medical records. RESULTS: 112 patients with dementia were found. The
      sensitivity of the general practitioners' judgment of dementia was 48.2% and the
      specificity 99.6%. The documentation rate of dementia was 73% in severe, 46% in
      moderate and 33% in mild dementia. A greater proportion of the patients with
      undocumented dementia were male (P = 0.003), lived at home (P = 0.003), coped
      better with the instrumental activities of daily living (P = 0.006), had more
      depression (P = 0.029) and milder dementia (P = 0.005) than patients with
      documented dementia. Thyroid stimulating hormone was measured in 51% of the
      patients with suspected memory impairment or dementia, B12 vitamin in 20%, and
      serum calcium in 18%. Twenty-eight per cent of the patients had been tested for
      cognitive function, 68% for depressive symptoms, and 88% for social abilities.
      Forty-two per cent of patients were referred to a specialist, 32% of patients who
      were over 75 years. CONCLUSIONS: less than half of the patients with dementia had
      their diagnosis documented in primary care medical records. Documentation
      increased in more advanced dementia. The diagnostic evaluations for reversible
      causes of dementia were insufficient in primary care, and they were done at a
      late phase of cognitive impairment.

PMID- 14600002
TI  - A comparison of health-related quality of life of elderly and younger insulin
      treated adults with diabetes.
AB  - BACKGROUND: diabetes is a significant disease of elderly people, an age group
      whose numbers will double over the next 20-30 years. Yet studies which assess
      diabetes-related quality of life have rarely included elderly participants.
      OBJECTIVES: to compare and contrast the health-related quality of life of elderly
      (> or = 65 years) and younger individuals with diabetes using reliable and valid
      assessment tools. METHODS: 191 adults (> or = 30 years) with diabetes currently
      on an insulin regimen were recruited. Medical and demographic data were gathered
      from the medical chart. Participants completed a generic quality of life measure
      (SF-36) and 3 diabetes-specific measures. Statistical analyses compared adults
      (30-64 years) to elderly adults (> or = 65 years). RESULTS: on the generic SF-36,
      physical and mental summary scores did not differ. However, elderly participants
      reported greater role limitations due to physical problems, and better social
      function. On diabetes-specific measures, elderly participants reported higher
      satisfaction with diabetes-related aspects of their lives, less diabetes-related
      emotional distress, and better ability to cope with their diabetes. CONCLUSIONS:
      the differences that did emerge between the two groups suggest that, though
      experiencing more limitations in their ability to function in their roles,
      elderly individuals with diabetes may still feel that they can cope with these
      limitations and thus manage the distress and lifestyle demands of the diabetes.
      The value of subscale analysis of the SF-36 and use of diabetes-specific health
      related quality of life measures is also affirmed.

PMID- 14600003
TI  - The predictive validity for mortality of the index of mobility-related limitation
      -results from the EPESE study.
AB  - BACKGROUND: self-reported disability reflects physical, environmental and
      attitudinal factors. We have previously reported the empirical identification of
      three simple tests to provide an index of (ambulatory) mobility-related
      physiological limitations (MOBLI). Evidence of the MOBLI 's responsiveness over
      time has been presented. Evidence of the predictive validity of the index is
      needed. OBJECTIVE: we aimed to measure the predictive validity for future
      mortality of the MOBLI and of self-reported mobility disability in a longitudinal
      cohort study. METHODS: data are from the sixth annual interview for two sites in
      the Established Populations for Epidemiologic Studies of the Elderly study.
      Included were 3,040 people, with information about self-reported walking
      difficulties, walking speed, time to complete five chair stands and peak
      expiratory flow. Age- and sex-adjusted death rates over a 4-year follow-up were
      computed, and proportional hazards regression models were used in the analysis.
      RESULTS: the MOBLI score is associated with subsequent mortality over 4 years,
      with evidence of a 'dose-response' relationship. The predictive value for
      mortality of the MOBLI score is similar to that of self-reported mobility
      disability in the studied population. CONCLUSIONS: the 'objective' MOBLI index
      has predictive validity as a continuous or dichotomised measure of the
      physiological component of mobility limitation in older populations. Given its
      empirical basis and face validity, predictive validity and responsiveness to
      change, MOBLI should be considered for local validation and use in
      epidemiological comparisons of older populations across countries or over longer
      periods of time.

PMID- 14600004
TI  - Women's health priorities and perceptions of care: a survey to identify
      opportunities for improving preventative health care delivery for older women.
AB  - BACKGROUND: women live longer than men but consistently report poorer health
      status and health-related quality of life. Information is scarce on what
      components of care women desire to help them meet the challenges of their later
      years. OBJECTIVES: to identify older women"s priorities for maintaining physical,
      emotional and social well-being in later years and to measure the extent to which
      women perceive that these priorities are being met by the health care system.
      METHODS: a cross-sectional survey of community-dwelling women aged 55-93 years
      old (n = 609, mean age 70). Women attendees of outpatient medical clinics were
      invited to fill out a written questionnaire on health priorities and perceptions
      of care. Mismatches between the care that women desired and the care they
      perceived to be receiving were identified. Predictors of unmet priorities were
      evaluated. SETTING: the Greater Montreal Area in Quebec, Canada. RESULTS: in
      general, respondents were more concerned about preventing disability than with
      developing certain diseases later in life. Women prioritised feeling validated in
      the health care relationship and having their health care provider see them as a
      whole person. Deficiencies in addressing memory loss, preserving mobility and
      function and treating urinary incontinence were highlighted. Women aged 75 years
      and older were less likely to perceive that their priorities were unmet compared
      to women aged 55-74 years (OR 0.571; 95% confidence interval 0.404-0.808), when
      adjusting for other socio-demographic and health variables. CONCLUSIONS:
      Opportunities exist to improve the preventive health care that women are
      receiving to promote healthy ageing. Women aged 55-74 should especially be
      targeted for interventions to prevent disability in later life.

PMID- 14600005
TI  - Chronic bronchitis in an elderly population.
AB  - BACKGROUND: in order to describe the prevalence and prognostic implications of
      chronic bronchitis in individuals 65 years or older we analysed data from The
      Copenhagen City Heart Study. METHODS: the population was studied in 1976-1978
      resurveyed in 1981-1983 and 1991-1994 and followed with regard to survival for up
      to 12 years. Approximately 3,700 elderly participants with a mean age of 76 years
      were available for analyses. RESULTS: the prevalence of chronic bronchitis was
      13.0% in women and 18.6% in men. Multiple logistic regression yielded the
      following predictors for chronic bronchitis: male gender (odds ratio with 95%
      confidence interval = 1.1 (0.9-1.3)), previous smoking odds ratio = 1.7 (1.2
      2.2), present smoking odds ratio = 2.1 (2.1-3.8), previous exposure to dusts and
      fumes (odds ratio = 2.2 (1.7-2.7)), chest infections in childhood (odds ratio =
      2.1 (1.6-2.9)), more than 6 chest infections in previous 10 years (odds ratio =
      6.2 (4.1-9.2)) and alcohol consumption of more than 3 drinks a day (odds ratio =
      1.8 (1.3-2.3)). Chronic bronchitis was a significant predictor of both subsequent
      respiratory infections and survival. After adjustment for age, smoking and lung
      function, a Cox regression showed that chronic bronchitis was significantly
      related to mortality from all causes with a hazard ratio with 95% confidence
      interval = 1.3 (1.1-1.4), all benign respiratory diseases (hazard ratio = 2.0
      (1.6-2.7)), obstructive lung disease (hazard ratio = 2.5 (1.7-3.6)) and lung
      cancer (hazard ratio = 2.0 (1.4-2.9)). CONCLUSIONS: in an elderly population,
      chronic bronchitis is a prevalent condition with important prognostic
      implications.

PMID- 14600006
TI  - Comparison of balance in older people with and without visual impairment.
AB  - OBJECTIVE: a cross-sectional study was used to compare the balance ability of
      older people with and without visual impairment. SETTING: Tung Wah Group of
      Hospitals Jockey Club Rehabilitation Complex and the Pok Oi Hospital Jockey Club
      care and attention homes for aged individuals. SUBJECTS: a total of 66 subjects,
      65 years of age and older were divided into three groups based on their degree of
      visual impairment. METHODS: the directional Es chart was used to test the
      subjects ' visual acuity. Functional balance ability was measured using the Berg
      balance scale. Demographic characteristics and baseline variables such as lower
      extremity range of motion, muscle strength, and joint pain was assessed and
      compared between the groups. RESULTS: 66 older adults (43 women, 23 men) aged 69
      94 years of age participated in the study. The one-way ANOVA showed that the mean
      Berg balance scores were significantly different (F(2,63) = 19.19, P < 0.001).
      Post hoc tests showed that the group with no visual impairment had higher mean
      balance scores than the group with mild visual impairment (P = 0.04) and those
      with moderate visual impairment (P < 0.001). The balance scores for the group
      with mild visual impairment were also shown to be significantly difference from
      those of the group with moderate visual impairment (P = 0.003). Control of
      factors related to balance, such as range of motion, pain and strength, did not
      affect the analysis of variance analyses. CONCLUSIONS: balance was shown to be
      more impaired with greater visual impairment, which could result in falls and
      resultant injury. The findings suggest that early intervention to improve visual
      acuity in older people may be important.

PMID- 14600007
TI  - Is grip strength a useful single marker of frailty?
AB  - BACKGROUND: chronological age is widely used as a marker of frailty in clinical
      practice. However there can be wide variation in frailty between individuals of a
      similar age. Grip strength is a powerful predictor of disability, morbidity and
      mortality which has been used in a number of frailty scores but not as a single
      marker of frailty. OBJECTIVE: to investigate the potential of grip strength as a
      single marker of frailty in older people of similar chronological age. DESIGN:
      cross-sectional study with prospective collection of mortality data. SETTING:
      North Hertfordshire, UK. SUBJECTS: 717 men and women, aged 64-74, born and still
      living in North Hertfordshire, who took part in a previous study to investigate
      the relationship between size at birth and ageing processes in later life.
      METHODS: the number of significant associations between grip strength and the
      ageing markers was compared with numbers between chronological age and the ageing
      markers. RESULTS: in men, lower grip strength correlated significantly with ten
      ageing markers compared to chronological age which was significantly associated
      with seven. In women, there were six significant relationships for grip compared
      to three for age. The greater number of relationships between grip strength and
      ageing markers was not explained by the association between grip strength and
      age, and remained after adjustment for adult size. CONCLUSIONS: grip strength was
      associated with more markers of frailty than chronological age within the narrow
      age range studied. Grip strength may prove a more useful single marker of frailty
      for older people of similar age than chronological age alone. Its validity in a
      clinical setting needs to be tested.

PMID- 14600008
TI  - Risk factors for Clostridium difficile colonisation and toxin production.
AB  - OBJECTIVES: to examine risk factors for patients becoming Clostridium difficile
      culture and toxin positive. DESIGN: prospective cohort study. SETTING: two
      medicine for the elderly wards. PARTICIPANTS: patients admitted to the wards over
      a 17-month period. MEASUREMENT: presence of Clostridium difficile on culture of
      stool specimens and toxins A and/or B. Patient's age, sex, source of admission,
      antibiotic, laxative, antacid and steroid use, presence/absence of colonic
      disease, neoplasia, leukaemia and nasogastric or percutaneous endoscopic
      gastrostomy tube feeding. RESULTS: 390 of 865 patients admitted provided a total
      of 1003 faecal specimens. Age (OR 1.04, 95% CI 1.001-1.07 per year), admission
      from another hospital (OR 2.13, 95% CI 1.29-3.50), non-cephalosporin antibiotics
      (OR 2.08, 95% CI 1.25-3.46) and cephalosporin use (OR 8.45, 95% CI 2.99-23.9)
      increased risk of becoming Clostridium difficile culture positive. Becoming toxin
      positive was associated with antibiotic use only (OR 3.02, 95% CI 1.15-7.92),
      specifically amoxycillin (OR 8.72, 95% CI 1.66-45.9) and cephalosporins other
      than ceftriaxone (OR 7.28, 95% CI 1.34-39.6). CONCLUSION: different risk factors
      are important for the two stages leading to Clostridium difficile diarrhoea. Age,
      source of admission and third generation cephalosporins increase risk of becoming
      culture positive, whilst only antibiotic use is associated with the step of
      becoming toxin-positive. Understanding these differential risks may aid infection
      control strategies.

PMID- 14600010
TI  - The usefulness of carotid sinus massage in different patient groups.
AB  - AIM: to determine the positive yield of carotid sinus massage in different
      patient groups: unexplained syncope, falls, dizziness and controls. DESIGN:
      observational study. SETTING: teaching hospital. METHODS: we studied consecutive
      patients over the age of 60 years referred to the 'falls clinic' with a history
      of unexplained syncope, unexplained falls and unexplained dizziness. We also
      studied asymptomatic control subjects recruited from a general practice register
      aged 60 years and over. All patients and control subjects underwent a full
      clinical assessment (comprehensive history and detailed clinical examination
      including supine and erect blood pressure measurements) and 12-lead
      electrocardiography. We performed carotid sinus massage in the supine position
      for 5 seconds separately on both sides followed by repeating the procedure in the
      upright positions using a motorised tilt table. Heart rate and blood pressure
      were recorded using a cardiac monitor and digital plethysmography respectively.
      The test was considered positive if carotid sinus massage produced asystole with
      more than a 3 second pause (cardioinhibitory type of carotid sinus syndrome), or
      a fall in systolic blood pressure of more than 50 mmHg in the absence of
      significant cardioinhibition (vasodepressor type of carotid sinus syndrome) or
      where there was evidence of both vasodepressor and cardio-inhibition as above
      (mixed type). RESULTS: we studied 44 asymptomatic control subjects and 221
      symptomatic patients (130 with unexplained syncope, 41 with unexplained falls and
      50 with unexplained dizziness). In the overall symptomatic patient group, the
      positive yield (any type of carotid sinus syndrome) was 17.6% (95% CI = 12.7
      22.5). The positive yield in men (26.3% (95% CI = 16.4-36.2)) was twice that in
      women (13.1% (95% CI = 7.6-18.6)) (P = 0.014). Overall any type of carotid sinus
      syndrome was present in 22.3% (n = 29) of the syncope group, 17.1% (n = 7) in the
      unexplained fallers group and 6% (n = 3) in the dizziness group. We also found
      that no women with unexplained dizziness had a positive carotid sinus massage
      test. None of the controls demonstrated a positive response. None of the subjects
      suffered any complications during or after the test. CONCLUSION: the positive
      yield of carotid sinus massage in symptomatic patients was 17.6% with the yield
      in men being twice that in women. None of the asymptomatic control subjects
      demonstrated a positive response. The yields in unexplained syncope and
      unexplained falls patients were around 4-fold and 3-fold higher respectively than
      in unexplained dizziness patients. The positive yield in women with unexplained
      dizziness (without a definite history of syncope and falls) is zero. Hence,
      carotid sinus massage in older adults should particularly be targeted at patients
      with unexplained syncope and unexplained falls.

PMID- 14600009
TI  - Seasonal changes in platelets, fibrinogen and factor VII in elderly people.
AB  - BACKGROUND: an increase in mean platelet volume and a decrease in platelet total
      have been reported following stroke and increased mean platelet volume in acute
      myocardial infarction has been shown to be predictive of mortality. OBJECTIVE:
      given the established seasonal variation in morbidity and mortality from
      cardiovascular disease and various risk factors for the disease, we explored the
      seasonal variation in mean platelet volume and platelet total. METHODS: we
      assessed levels of platelet count, platelet volume, fibrinogen, factor VII, core
      body and ambient temperatures in 54 healthy community dwelling elderly volunteers
      over a period of 1 year. We used cosinor rhythmometry to quantify and compare the
      seasonal rhythms. RESULTS: we found significant seasonal variation in fibrinogen,
      mean platelet volume and core body temperature all of which peaked synchronously
      in May/June, in a year with an atypically mild winter and hot summer. Platelet
      total and factor VII did not exhibit a seasonal rhythm. CONCLUSIONS: we conclude
      that the synchrony between peak size of platelets and peak level of fibrinogen
      will significantly increase the likelihood of thrombotic events. These results
      provide further evidence of a seasonal pro-thrombotic state, which has a complex
      relationship with temperature.

PMID- 14600011
TI  - Molecular epidemiology of asymptomatic bacteriuria in the elderly.
AB  - OBJECTIVES: to determine the incidence and the dynamics of asymptomatic
      bacteriuria in ambulatory nursing home residents, and to characterise bacteria
      according to their phenotype and genotype. DESIGN: an 18 months prospective
      longitudinal study. SUBJECTS: 42 nursing home residents (31 female, 11 males)
      without indwelling catheters. METHODS: urine was sampled every 3 months.
      Antibiograms, biotyping and ribotyping were performed. RESULTS: the cumulative
      percent of infection for females and males was 75% and 27% respectively.
      Osteoporosis was associated with bacteriuria. Ribotypes of consecutive
      Escherichia coli isolates indicated that each patient harboured a different
      strain. CONCLUSIONS: asymptomatic bacteriuria in the elderly is a dynamic and
      transient phenomenon. Osteoporosis is common among this population. Ribotyping is
      a powerful tool in the elucidation of the epidemiology of this bacteriuria.

PMID- 14600012
TI  - No gag, no food.

PMID- 14600013
TI  - Factors associated with the use of hormone replacement therapy among older women.

PMID- 14600014
TI  - IGF-1 levels, leg extensor power and physical performance after proximal femoral
      fracture.

PMID- 14600015
TI  - A rationale for vitamin D prescribing in a falls clinic population.

PMID- 14600017
TI  - Nursing home prescribing indicators.

PMID- 14600018
TI  - Spirometry in old age.

PMID- 14600020
TI  - Attitudes to monitoring of anticoagulation are influenced by age.

PMID- 14600022
TI  - Functional haplotypes of the RET proto-oncogene promoter are associated with
      Hirschsprung disease (HSCR).
AB  - The activation of the RET signaling pathway during embryogenesis is a crucial
      prerequisite for a directional migration of enteric nervous system progenitor
      cells. Loss-of-function germline mutations of the RET proto-oncogene are reported
      in familial and sporadic cases of Hirschsprung disease (HSCR) with a variable
      frequency. Furthermore, variants of several RET polymorphisms are over- or under
      represented in HSCR populations. Specifically, the c.135A RET variant has been
      previously shown to be strongly associated with the HSCR phenotype. We have
      reported an HSCR-phenotype modifying effect of the RET c.135G>A polymorphism due
      to a within-gene interaction in patients harboring RET germline mutations, yet
      the function of the c.135G>A variant is unknown. The basic RET promoter region
      was investigated by DNA sequencing approach in 80 HSCR patients. Identified
      polymorphisms were genotyped in the HSCR and in a control population and
      haplotypes were reconstructed. The dual-luciferase assay was used to evaluate the
      activity of different RET promoter haplotypes. We demonstrate that variants of
      two RET promoter polymorphisms -5G>A and -1C>A from the transcription start site
      are associated with HSCR. Furthermore, the -5G>A polymorphism is in strong
      linkage disequilibrium with the c.135G>A polymorphism. The promoter haplotype -5/
      1AC associated with HSCR has a significantly lower activity in an in vitro dual
      luciferase expression assay compared with those haplotypes identified in the
      majority of normal controls. These data suggest a role for RET haplotypes
      containing the -5A promoter variant in the etiology of HSCR.

PMID- 14600023
TI  - Pin1 modulates the structure and function of human RNA polymerase II.
AB  - The C-terminal domain of the RNA polymerase (RNAP) II largest subunit (CTD) plays
      critical roles both in transcription of mRNA precursors and in the processing
      reactions needed to form mature mRNAs. The CTD undergoes dynamic changes in
      phosphorylation during the transcription cycle, and this plays a significant role
      in coordinating its multiple activities. But how these changes themselves are
      regulated is not well understood. Here we show that the peptidyl-prolyl isomerase
      Pin1 influences the phosphorylation status of the CTD in vitro by inhibiting the
      CTD phosphatase FCP1 and stimulating CTD phosphorylation by cdc2/cyclin B. This
      is reflected in vivo by accumulation of hypophosphorylated RNAP II in pin1-/-
      cells, and of a novel hyper-hyperphosphorylated form in cells induced to
      overexpress Pin1. This hyper-hyperphosphorylated form of RNAP II also accumulates
      in M-phase cells, in a Pin1-dependent manner, and associates specifically with
      Pin1. Functionally, we find that Pin1 overexpression specifically inhibits
      ongoing transcription of mRNA precursors in vivo and both transcription and RNAP
      II-stimulated pre-mRNA splicing in cell extracts. Pin1 thus plays a significant
      role in regulating RNAP II CTD structure and function.

PMID- 14600024
TI  - Position of eukaryotic initiation factor eIF1 on the 40S ribosomal subunit
      determined by directed hydroxyl radical probing.
AB  - Eukaryotic initiation factor (eIF) eIF1 maintains the fidelity of initiation
      codon selection by enabling 43S complexes to reject codon-anticodon mismatches,
      to recognize the initiation codon context, and to discriminate against
      establishing a codon-anticodon interaction with AUGs located <8 nt from the 5'
      end of mRNA. To understand how eIF1 plays its discriminatory role, we determined
      its position on the 40S ribosomal subunit using directed hydroxyl radical
      cleavage. The cleavage of 18S rRNA in helices 23b, 24a, and 44 by hydroxyl
      radicals generated from Fe(II) tethered to seven positions on the surface of eIF1
      places eIF1 on the interface surface of the platform of the 40S subunit in the
      proximity of the ribosomal P-site. The position of eIF1 on the 40S subunit
      suggests that although eIF1 is unable to inspect the region of initiation codon
      directly, its position close to the P-site is very favorable for an indirect
      mechanism of eIF1's action by influencing the conformation of the platform of the
      40S subunit and the positions of mRNA and initiator tRNA in initiation complexes.
      Unexpectedly, the position of eIF1 on the 40S subunit was strikingly similar to
      the position on the 30S ribosomal subunit of the sequence and structurally
      unrelated C-terminal domain of prokaryotic initiation factor IF3, which also
      participates in initiation codon selection in prokaryotes.

PMID- 14600026
TI  - Untraditional methods for targeting the kidney in transgenic mice.
AB  - With the completion of the human genome project and the sequencing of many
      genomes of experimental models, there is a pressing need to determine the
      physiological relevance of newly identified genes. Gene-targeting approaches have
      become an important tool in our arsenal to dissect the significance of genes
      expressed in many tissues. A wealth of experimental models has been made to
      assess the role of gene expression in renal function and development. The
      development of new and informative models is presently limited by the anatomic
      complexity of the kidney and the lack of cell-specific promoters to target the
      numerous diverse cell types in that organ. Because of this, new approaches may
      have to be developed. In this review, we will discuss several untraditional
      methods to target gene expression to the kidney. These approaches should provide
      some additional tricks and tools to help in developing additional informative
      models for studying renal physiology.

PMID- 14600027
TI  - Murine models of polycystic kidney disease: molecular and therapeutic insights.
AB  - Numerous murine (mouse and rat) models of polycystic kidney disease (PKD) have
      been described in which the mutant phenotype results from a spontaneous mutation
      or engineering via chemical mutagenesis, transgenic technologies, or gene
      specific targeting in mouse orthologs of human PKD genes. These murine phenotypes
      closely resemble human PKD, with common abnormalities observed in tubular
      epithelia, the interstitial compartment, and the extracellular matrix of cystic
      kidneys. In both human and murine PKD, genetic background appears to modulate the
      renal cystic phenotype. In murine models, these putative modifying effects have
      been dissected into discrete factors called quantitative trait loci and
      genetically mapped. Several lines of experimental evidence support the hypothesis
      that PKD genes and their modifiers may define pathways involved in cystogenesis
      and PKD progression. Among the various pathway abnormalities described in murine
      PKD, recent provocative data indicate that structural and/or functional defects
      in the primary apical cilia of tubular epithelia may play a key role in PKD
      pathogenesis. This review describes the most widely studied murine models;
      highlights the data regarding specific gene defects and genetic modifiers;
      summarizes the data from these models that have advanced our understanding of PKD
      pathogenesis; and examines the effect of various therapeutic interventions in
      murine PKD.

PMID- 14600025
TI  - Crystal structure of a beta-catenin/axin complex suggests a mechanism for the
      beta-catenin destruction complex.
AB  - The "beta-catenin destruction complex" is central to canonical Wnt/beta-catenin
      signaling. The scaffolding protein Axin and the tumor suppressor adenomatous
      polyposis coli protein (APC) are critical components of this complex, required
      for rapid beta-catenin turnover. We determined the crystal structure of a complex
      between beta-catenin and the beta-catenin-binding domain of Axin (Axin-CBD). The
      Axin-CBD forms a helix that occupies the groove formed by the third and fourth
      armadillo repeats of beta-catenin and thus precludes the simultaneous binding of
      other beta-catenin partners in this region. Our biochemical studies demonstrate
      that, when phosphorylated, the 20-amino acid repeat region of APC competes with
      Axin for binding to beta-catenin. We propose that a key function of APC in the
      beta-catenin destruction complex is to remove phosphorylated beta-catenin product
      from the active site.

PMID- 14600028
TI  - Oxidative stress in the pathogenesis of experimental mesangial proliferative
      glomerulonephritis.
AB  - Reactive oxygen species (ROS) are increasingly believed to be important
      intracellular signaling molecules in mitogenic pathways involved in the
      pathogenesis of glomerulonephritis (GN). We explored the effects of the
      antioxidants alpha-lipoic acid and N-acetyl-l-cysteine on ERK activation in
      cultured mesangial cells and the role of ERK activation in the severity of
      glomerular injury in a rat model of anti-Thy 1 GN. In cultured mesangial cells,
      growth factors stimulated ERK phosphorylation by 150-450%. Antioxidants reduced
      this increase by 50-60%. Induction of anti-Thy 1 nephritis in rats led to a 210%
      increase in glomerular ERK phosphorylation. This increase in phosphorylated ERK
      was reduced by 50% in animals treated with alpha-lipoic acid. Treatment with
      alpha-lipoic acid resulted in significant improvement of glomerular injury.
      Cellular proliferation was reduced by 100%, and the number of proliferating cell
      nuclear antigen-positive cells was reduced by 64%. The increased expression of
      glomerular transforming growth factor-beta1 protein and mRNA in rats with anti
      Thy 1 nephritis was significantly attenuated and mesangial cell transformation
      into myofibroblasts was completely prevented by treatment with alpha-lipoic acid.
      The effects of alpha-lipoic acid were at least partially due to inhibition of
      oxidative stress. In rats with anti-Thy 1 nephritis, ROS production was increased
      400-500%, and this increase was inhibited by 55% by treatment with alpha-lipoic
      acid. We suggest that ROS may mediate glomerular injury by inducing ERK
      phosphorylation. alpha-Lipoic acid should be considered a potential therapeutic
      agent in certain types of human GN.

PMID- 14600029
TI  - A1 adenosine receptor knockout mice exhibit increased renal injury following
      ischemia and reperfusion.
AB  - Controversy exists regarding the effect of A1 adenosine receptor (AR) activation
      in the kidney during ischemia and reperfusion (I/R) injury. We sought to further
      characterize the role of A1 ARs in modulating renal function after I/R renal
      injury using both pharmacological and gene deletion approaches in mice. A1 AR
      knockout mice (A1KO) or their wild-type littermate controls (A1WT) were subjected
      to 30 min of renal ischemia. Some A1WT mice were subjected to 30 min of renal
      ischemia with or without pretreatment with 1,3-dipropyl-8-cyclopentylxanthine
      (DPCPX) or 2-chrolo-cyclopentyladenosine (CCPA), selective A1 AR antagonist and
      agonist, respectively. Plasma creatinine and renal histology were compared 24 h
      after renal injury. A1KO mice exhibited significantly higher creatinines and
      worsened renal histology compared with A1WT controls following renal I/R injury.
      A1WT mice pretreated with the A1 AR antagonist or agonist demonstrated
      significantly worsened or improved renal function, respectively, after I/R
      injury. In addition, A1WT mice pretreated with DPCPX or CCPA showed significantly
      increased or reduced markers of renal inflammation, respectively (renal
      myeloperoxidase activity, renal tubular neutrophil infiltration, ICAM-1, TNF
      alpha, and IL-1beta mRNA expression), while demonstrating no differences in
      indicators of apoptosis. In conclusion, we demonstrate that endogenous or
      exogenous preischemic activation of A1 ARs protects against renal I/R injury in
      vivo via mechanisms leading to decreased necrosis and inflammation.

PMID- 14600030
TI  - Kidney injury molecule-1: a tissue and urinary biomarker for nephrotoxicant
      induced renal injury.
AB  - Nephrotoxicity is a common side effect of therapeutic interventions,
      environmental insults, and exposure to toxicants in the workplace. Although
      biomarkers for nephrotoxicity are available, they often lack sensitivity and are
      not specific as indicators of epithelial cell injury. Kidney injury molecule-1
      (Kim-1) is a type 1 membrane protein with extracellular immunoglobulin and mucin
      domains. The mRNA and protein for Kim-1 are expressed at very low levels in
      normal rodent kidney, but expression increases dramatically after injury in
      proximal tubule epithelial cells in postischemic rodent kidney and in humans
      during ischemic acute renal failure. To evaluate the utility of Kim-1 as a
      biomarker for other types of renal injury, we analyzed tissue and urinary
      expression in response to three different types of nephrotoxicants in the rat: S
      (1,1,2,2-tetrafluoroethyl)-l-cysteine (TFEC), folic acid, and cisplatin. Marked
      increases in Kim-1 expression were confirmed by immunoblotting in all three
      models. The protein was shown to be localized to the proximal tubule epithelial
      cell by immunofluorescence. Furthermore, Kim-1 protein was detected in urine of
      toxicant-treated rats. The temporal pattern of expression in response to TFEC is
      similar to the Kim-1 expression pattern in the postischemic kidney. In folic acid
      treated kidneys, Kim-1 is clearly localized to the apical brush border of the
      well-differentiated proximal tubular epithelial cells. After folic acid
      treatment, expression of Kim-1 is present in the urine despite no significant
      increase in serum creatinine. Cisplatin treatment results in early detection of
      urinary Kim-1 protein and diffuse Kim-1 expression in S3 cells of the proximal
      tubule. Kim-1 can be detected in the tissue and urine on days 1 and 2 after
      cisplatin administration, occurring before an increase in serum creatinine. The
      upregulation of expression of Kim-1 and its presence in the urine in response to
      exposure to various types of nephrotoxicants suggest that this protein may serve
      as a general biomarker for tubular injury and repair processes.

PMID- 14600031
TI  - The chemokine KC regulates HGF-stimulated epithelial cell morphogenesis.
AB  - Hepatocyte growth factor (HGF) induces migration, proliferation, and branching in
      renal epithelial cells from the inner medullary collecting duct (mIMCD-3 cells).
      Microarray analysis after HGF stimulation of these cells revealed upregulation of
      the chemokine KC. We found that both the message and protein levels of KC are
      increased after HGF treatment and that mIMCD-3 cells express the KC receptor
      CXCR2. Treatment with KC results in stimulation of mIMCD-3 cell proliferation but
      has no effect on basal rates of cell migration or branching morphogenesis. In
      contrast to its known stimulatory effect on neutrophil migration, KC markedly
      inhibits HGF-mediated cell migration and branching morphogenesis, resulting in
      shorter tubules with fewer branch points. Examination of the mechanism of this
      effect reveals that KC does not alter phosphorylation of the c-met receptor or
      the initial activation of the MAPK or phosphoinositide 3-kinase (PI 3-K)
      signaling pathways. However, sustained activation of the PI 3-K pathway by HGF
      was inhibited by treatment with KC, and mimicking this effect by treatment with
      LY-294002 2 h after HGF stimulation reproduced the inhibition of HGF-stimulated
      branching morphogenesis. These data demonstrate that HGF-mediated KC production
      can act in an autocrine fashion to downregulate excessive branching and migration
      of renal epithelial cells in response to HGF, while still supporting cell
      proliferation. These characteristics may play a role in modulating the response
      to HGF during developmental tubule formation and/or during the repair of the
      tubular architecture following injury.

PMID- 14600032
TI  - Water turnover in 458 American adults 40-79 yr of age.
AB  - Despite recent interest in water intake, few data are available on water
      metabolism in adults. To determine the average and range of usual water intake,
      urine output, and total body water, we administered 2H oxide to 458
      noninstitutionalized 40- to 79-yr-old adults living in temperate climates. Urine
      was collected in a subset of individuals (n = 280) to measure 24-h urine
      production using p-aminobenzoic acid to ensure complete collection. Preformed
      water intake was calculated from isotopic turnover and corrected for metabolic
      water and insensible water absorption from humidity. Preformed water intake,
      which is water from beverages and food moisture, averaged 3.0 l/day in men
      (range: 1.4-7.7 l/day) and 2.5 l/day in women (range: 1.2-4.6 l/day). Preformed
      water intake was lower in 70- to 79 (2.8 l/day)- than in 40- to 49-yr-old men and
      was lower in 70- to 79 (2.3 l/day)- than in 40- to 49- and 50- to 59-yr-old
      women. Urine production averaged 2.2 l/day in men (range: 0.6-4.9 l/day) and 2.2
      l/day in women (0.9-6.0 l/day). There were no age-related differences in results
      in women, but 60- to 69-yr-old men had significantly higher urine output than 40-
      to 49- and 50- to 59-yr-old men. Only the 70- to 79-yr-old group included
      sufficient blacks for a racial analysis. Blacks in this age group showed
      significantly lower preformed water intake than did whites. Whites had
      significantly higher water turnover rates than blacks as well. Multivariate
      regression indicated that age, weight, height, and body mass index explained <12%
      of the gender-specific variance in water input or urine output, yet repeat
      measures indicated that within-individual coefficient of variation was 8% for
      preformed water intake (n = 22) and 9% for 24-h urine production (n = 222). These
      results demonstrate that water turnover is highly variable among individuals and
      that little of the variance is explained by anthropometric parameters.

PMID- 14600033
TI  - ROMK is required for expression of the 70-pS K channel in the thick ascending
      limb.
AB  - Apical potassium recycling is crucial for salt transport by the thick ascending
      limb (TAL). Loss-of-function mutations in the K channel, ROMK (Kir1.1; KCNJ1),
      cause Bartter syndrome, a genetically heterogeneous disorder characterized by
      severe reduction in salt absorption by the TAL, Na wasting, polyuria, and
      hypokalemic alkalosis. ROMK(-/-) null mice exhibit a Bartter phenotype and lack
      the small-conductance (30-pS) apical K channel (SK) in the TAL. However, a
      distinct 70-pS K channel can also significantly contribute to the apical
      conductance of TAL. We now examine the effect of ROMK deletion on the functional
      expression of the 70-pS K channel in the TAL. Functional expression of the 70-pS
      K channel was low [average channel activity (NP(o)) = 0.02] in ROMK(+/+) mice on
      a control K diet but increased to 0.27 by high-K intake for 2 wk. In contrast,
      the high-K diet decreased NP(o) of SK by approximately 30%, from 2.04 to 1.44. In
      ROMK heterozygous (+/-) mice on a control K diet, SK activity was about one-half
      of that observed in ROMK(+/+) mice (0.95 vs. 2.04). The high-K diet also reduced
      SK activity in ROMK(+/-) mice by approximately 40% (from 0.95 to 0.55) but
      increased NP(o) of the 70-pS K channel from 0 to 0.09 in ROMK(+/-) mice. This
      corresponds to approximately 30% of channel activity (NP(o) = 0.27) observed in
      ROMK(+/+) mice. Neither the 70-pS nor the 30-pS K channels were observed in TAL
      cells from ROMK(-/-) mice on either the normal or high-K diets. Thus functional
      expression of the 70-pS K channel is enhanced by increasing dietary K and
      requires expression of ROMK. It is likely that ROMK forms a critical subunit of
      the 70-pS K channel, accounting for the loss of apical K secretory channel
      activity in ROMK Bartter syndrome.

PMID- 14600034
TI  - 1,25-Dihydroxyvitamin D3 decreases podocyte loss and podocyte hypertrophy in the
      subtotally nephrectomized rat.
AB  - 1,25(OH)(2)D(3) has antiproliferative effects and promotes cell differentiation.
      This consideration has provided the rationale for studies in subtotally
      nephrectomized rats showing that 1,25(OH)(2)D(3) interfered with
      glomerulosclerosis. The cellular mechanisms involved have remained obscure,
      however. It was the purpose of the present study to assess glomerular structure
      and cellular composition in subtotally nephrectomized (SNX) rats treated with
      nonpharmacological doses of 1,25(OH)(2)D(3). Male Sprague-Dawley rats were sham
      operated (sham) or underwent SNX under general anesthesia and received either
      solvent or 1,25(OH)(2)D(3) (3 ng.100 g body wt(-1).day(-1) sc). Blood pressure
      (BP) and albuminuria were measured. After 16 wk, the remnant renal tissue was
      perfusion fixed and morphometric and stereological measurements were carried out.
      The expression of proliferating cellular antigen (PCNA), cyclin-dependent kinase
      inhibitor p27, Wilms tumor gene (WT1), and desmin, a marker of early podocyte
      damage, was investigated by immunohistology. BP, serum creatinine, and urinary
      albumin excretion were significantly higher in SNX than in sham rats. Albuminuria
      was significantly lower in SNX+1,25(OH)(2)D(3) compared with SNX+solvent rats.
      Mean glomerular tuft volume was significantly higher in SNX+solvent (2.69 +/-
      0.21 gx 10(6) microm(3)) than in sham rats (1.44 +/- 0.17 and 1.28 +/- 0.14 x
      10(6) microm(3)); it was significantly (P < 0.05) lower in SNX+1,25(OH)(2)D(3)
      rats (1.81 +/- 0.16 x 10(6) microm(3)). The main finding was a significantly
      higher number of podocytes in SNX+1,25(OH)(2)D(3) (88 +/- 9) and sham (98 +/- 17)
      compared with SNX+solvent rats (81 +/- 8.7). In parallel, the increase in
      podocyte volume in SNX+solvent rats was abrogated by treatment with
      1,25(OH)(2)D(3), and immunohistochemistry revealed less expression of desmin,
      PCNA, and p27, suggesting less podocyte injury and activation of the cyclin
      cascade. This study identifies the podocyte as an important target cell for the
      renoprotective action of 1,25(OH)(2)D(3). This notion is suggested by less
      evidence of podocyte injury, decreased podocytes loss, and abrogation of podocyte
      hypertrophy, findings that may also explain less pronounced albuminuria and
      glomerulosclerosis.

PMID- 14600035
TI  - Serial determination of glomerular filtration rate in conscious mice using FITC
      inulin clearance.
AB  - Two nonradioactive methods for determining glomerular filtration rate (GFR) in
      conscious mice using FITC-labeled inulin (FITC-inulin) were evaluated. The first
      method measured GFR using clearance kinetics of plasma FITC-inulin after a single
      bolus injection. Based on a two-compartment model, estimated GFR was 236.69 +/-
      16.55 and 140.20 +/- 22.27 microl/min in male and female C57BL/6J mice,
      respectively. Total or (5/6) nephrectomy reduced inulin clearance to 0 or 32.80
      +/- 9.32 microl/min, respectively. Conversely, diabetes mellitus induced by
      streptozotocin was associated with increased GFR. The other approach measured
      urinary inulin clearance using intraperitoneal microosmotic pumps to deliver FITC
      inulin and metabolic cages to collect timed urine samples. This approach yielded
      similar GFR values of 211.11 +/- 26.56 and 157.36 +/- 20.02 microl/min in male
      and female mice, respectively. These studies demonstrate the feasibility of
      repeated nonisotopic measurement of inulin clearance in conscious mice.

PMID- 14600037
TI  - Coronary heart disease mortality in Russia and Eastern Europe.

PMID- 14600038
TI  - Limits and access to health care.

PMID- 14600039
TI  - Demographics and tobacco outlet density.

PMID- 14600041
TI  - Valuing families and meeting them where they are.

PMID- 14600042
TI  - Practice is the purpose of public health.

PMID- 14600043
TI  - A role for public health research in shaping adolescent health policy.

PMID- 14600044
TI  - An interview with Dr. Lester Breslow [interview by JoAna Stallworth and Jeffery
      L. Lennon].

PMID- 14600045
TI  - Navigating the road to implementation of the Health Insurance Portability and
      Accountability Act.
AB  - The Health Insurance Portability and Accountability Act of 1996 (HIPAA) has a
      profound impact on safety net providers. To help agencies afford expert
      consultation and provide the opportunity for collaboration, a regional health
      foundation has created the first model in the nation to bring together safety net
      providers to work toward implementation of the HIPAA.

PMID- 14600046
TI  - Focusing on HIV/AIDS in Africa.

PMID- 14600047
TI  - The American College of Obstetricians and Gynecologists and the evolution of
      abortion policy, 1951-1973: the politics of science.
AB  - The autonomy granted to physicians is based on the claim that their decisions are
      grounded in scientific principles. But a case study of the evolution of the
      American College of Obstetricians and Gynecologists' abortion policy between 1951
      and 1973 shows that decisions were only secondarily determined by science. The
      principal determinant was the need to preserve physician autonomy over the
      organization and delivery of services. As a result, the organization representing
      physicians who specialized in women's reproductive health was marginal to the
      struggle for legalized abortion. But, the profession was central to decisions
      about whether physicians would perform abortions and how they would be done. This
      case study finding has implications for understanding the role that organized
      medicine might take in the ongoing debates about national health policy.

PMID- 14600048
TI  - Contextual influences on reproductive wellness in northern India.
AB  - OBJECTIVES: There has been a growing recognition of the importance of contextual
      influences on health outcomes. This article examines community-level influences
      on 5 reproductive wellness outcomes in Uttar Pradesh, India. METHODS: Multilevel
      modeling is used to estimate household and community-level effects on wellness,
      with hierarchically organized data from a statewide survey of villages, urban
      blocks, households, women, health providers, and staff. RESULTS: The household
      and community have a strong contextual influence on wellness, although the models
      explain more of the variation in outcomes between households than between
      communities. CONCLUSIONS: Communities influence wellness outcomes through the
      socioeconomic environment and the characteristics of the health infrastructure.
      The specific dimensions of the community and health infrastructure varied between
      the outcomes.

PMID- 14600049
TI  - New inroads in preventing adolescent drug use: results from a large-scale trial
      of project ALERT in middle schools.
AB  - OBJECTIVES: We evaluated the revised Project ALERT drug prevention program across
      a wide variety of Midwestern schools and communities. METHODS: Fifty-five South
      Dakota middle schools were randomly assigned to program or control conditions.
      Treatment group students received 11 lessons in 7th grade and 3 more in 8th
      grade. Program effects for 4276 8th-graders were assessed 18 months after
      baseline. RESULTS: The revised Project ALERT curriculum curbed cigarette and
      marijuana use initiation, current and regular cigarette use, and alcohol misuse.
      Reductions ranged from 19% to 39%. Program effects were not significant for
      initial and current drinking or for current and regular marijuana use.
      CONCLUSIONS: School-based drug prevention programs can prevent occasional and
      more serious drug use, help low- to high-risk adolescents, and be effective in
      diverse school environments.

PMID- 14600050
TI  - Effects of a social-network method for group assignment strategies on peer-led
      tobacco prevention programs in schools.
AB  - OBJECTIVES: Our study tested the effectiveness of network methods for identifying
      opinion leaders and for constructing groups. METHODS: Three conditions-random,
      teacher, and network--ere randomly assigned to 84 6th-grade classrooms within 16
      schools. Pre- and postcurriculum data on mediators of tobacco use were collected
      from 1961 students. Peer leaders in the network condition were identified by
      student nominations, and those leaders were matched with the students who
      nominated them. RESULTS: Students in the network condition relative to the random
      condition liked the prevention program more and had improved attitudes (beta = 
      0.06; P <.01), improved self-efficacy (beta = -0.10; P <.001), and decreased
      intention to smoke (adjusted odds ratio [OR] = 0.46; 95% confidence interval [CI]
      = 0.38, 0.55). CONCLUSIONS: The network method was the most effective way to
      structure the program. Future programs may refine this technique and use it in
      other settings.

PMID- 14600051
TI  - The public health impact of socioeconomic status on adolescent depression and
      obesity.
AB  - OBJECTIVES: We examined the public health impact of the socioeconomic status
      (SES) gradient on adolescents' physical and mental health. METHODS: Population
      attributable risk (PAR) for household income and parental education were
      calculated relative to depression and obesity among a nationally representative
      sample of 15,112 adolescents. RESULTS: PARs for income and education were large.
      Across each gender and race/ethnicity group, the PAR for education tended to
      exceed that for income. For depression, the adjusted PAR for income was 26%, and
      the PAR for education was 40%; for obesity, the adjusted PAR for income was 32%,
      and the PAR for education was 39%. CONCLUSIONS: SES is associated with a large
      proportion of the disease burden within the total population.

PMID- 14600052
TI  - Adolescent health in the Caribbean: a regional portrait.
AB  - OBJECTIVES: This study assessed youth health in the Caribbean Community and
      Common Market countries and describes the prevalence of health-related factors.
      METHODS: We used a self-administered classroom questionnaire; questions addressed
      general health, health care, nutrition, sexual history, drug use, mental health,
      violence, family characteristics, and relationships with others. RESULTS: Most
      youths reported good health; however, 1 in 10 reported a limiting disability or
      significant health problems. Violence was a pervasive concern. Of those who
      reported history of sexual intercourse, many reported that their first
      intercourse was forced, and nearly half reported that they were aged 10 years or
      younger when they first had intercourse. CONCLUSIONS: Although most young people
      are healthy, problems indicate the importance of monitoring trends and designing
      effective youth health programs.

PMID- 14600053
TI  - Do risk factors for childhood infections and malnutrition protect against asthma?
      A study of Brazilian male adolescents.
AB  - OBJECTIVES: We studied the association between early life conditions and asthma
      in adolescence. METHODS: We conducted a population-based birth cohort study
      involving 2250 male 18-year-olds residing in Brazil. RESULTS: Approximately 18%
      of the adolescents reported having asthma. Several childhood factors were found
      to be significantly associated with increased asthma risk: being of high
      socioeconomic status, living in an uncrowded household, and children being
      breastfed for 9 months or longer. CONCLUSIONS: The present results are consistent
      with the "hygiene hypothesis," according to which early exposure to infections
      provides protection against asthma. The policy implications of our findings are
      unclear given that risk factors for asthma protect against serious childhood
      diseases in developing countries.

PMID- 14600054
TI  - Health and behavior risks of adolescents with mixed-race identity.
AB  - OBJECTIVES: This study compared the health and risk status of adolescents who
      identify with 1 race with those identifying with more than 1 race. METHODS: Data
      are derived from self-reports of race, using the National Longitudinal Study of
      Adolescent Health (Add Health), which provides a large representative national
      sample of adolescents in grades 7 through 12. Respondents could report more than
      1 race. RESULTS: Mixed-race adolescents showed higher risk when compared with
      single-race adolescents on general health questions, school experience, smoking
      and drinking, and other risk variables. CONCLUSIONS: Adolescents who self
      identify as more than 1 race are at higher health and behavior risks. The
      findings are compatible with interpreting the elevated risk of mixed race as
      associated with stress.

PMID- 14600056
TI  - Ethical issues in youth surveys: potentials for conducting a national
      questionnaire study on adolescent schoolchildren's sexual experiences with
      adults.
AB  - OBJECTIVES: We evaluated ethical constraints concerning youth surveys on child
      sexual abuse (CSA). METHODS: We reviewed internationally published studies and
      Danish regulations concerning school-based surveys conducted without active
      parental consent. RESULTS: Ethical constraints concerning participants in youth
      community studies have been scantily assessed. Danish legislation accords minors
      the right to be heard on issues concerning themselves. The anticipated societal
      benefits of children's participation in community studies justify conducting
      anonymous surveys among schoolchildren based upon their own informed consent.
      CONCLUSIONS: No ethical or legal objections were found to conducting an anonymous
      survey in Denmark on CSA among 9th-grade pupils without parental consent,
      provided that the survey was accompanied by an offer of counseling.

PMID- 14600055
TI  - Increasing Latino adolescents' adherence to treatment for latent tuberculosis
      infection: a controlled trial.
AB  - OBJECTIVES: We sought to determine the efficacy of coaching Latino adolescents
      with latent tuberculosis infection to adhere to isoniazid treatment. METHODS:
      Participants (n = 286) were randomly assigned to adherence coaching, attention
      control, or usual care groups. Adherence was measured via interviews and
      validated with urine assays. RESULTS: Coaching resulted in significant increases
      in adherence compared with attention and usual care groups. Bicultural
      adolescents were more likely to be adherent than those most or least
      acculturated. Age and risk behavior were negatively related to adherence.
      CONCLUSIONS: Coaching can increase Latino adolescents' adherence to treatment for
      latent tuberculosis infection and should contribute to tuberculosis control for
      adolescents at high risk of contracting the disease.

PMID- 14600057
TI  - Validity of assessments of youth access to tobacco: the familiarity effect.
AB  - OBJECTIVES: We examined the standard compliance protocol and its validity as a
      measure of youth access to tobacco. METHODS: In Study 1, youth smokers reported
      buying cigarettes in stores where they are regular customers. In Study 2, youths
      attempted to purchase cigarettes by using the Standard Protocol, in which they
      appeared at stores once for cigarettes, and by using the Familiarity Protocol, in
      which they were rendered regular customers by purchasing nontobacco items 4 times
      and then requested cigarettes during their fifth visit. RESULTS: Sales to youths
      aged 17 years in the Familiarity Protocol were significantly higher than sales to
      the same age group in the Standard Protocols (62.5% vs. 6%, respectively).
      CONCLUSIONS: The Standard Protocol does not match how youths obtain cigarettes.
      Access is low for stranger youths within compliance studies, but access is high
      for familiar youths outside of compliance studies.

PMID- 14600058
TI  - An outbreak of the severe acute respiratory syndrome: predictors of health
      behaviors and effect of community prevention measures in Hong Kong, China.

PMID- 14600059
TI  - New opportunities for integrated child health systems: results from the
      multifaceted pre-to-three program.

PMID- 14600060
TI  - Decreasing barriers for teens: Evaluation of a new teenage pregnancy prevention
      strategy in school-based clinics.

PMID- 14600061
TI  - Substance use among foreign-born youths in the United States: does the length of
      residence matter?

PMID- 14600062
TI  - Prevalence of episodic homelessness among adult childbearing women in
      Philadelphia, PA.

PMID- 14600063
TI  - Female-condom use in a gender-specific family planning clinic trial.
AB  - OBJECTIVES: We evaluated female-condom use among women participating in an
      HIV/STD intervention designed to reduce unprotected sex and expand prevention
      strategies. METHODS: Women (n = 360) were recruited from a family-planning clinic
      and were randomized into an 8- or 4-session intervention group or a control
      group. We conducted follow-up interviews at 1, 6, and 12 months. RESULTS: At 1
      month, the odds ratios of first-time female-condom use were 9.49 (95% confidence
      interval [CI] = 4.01, 22.20) in the 8-session group and 4.39 (95% CI = 1.84,
      10.49) in the 4-session group relative to controls. Repeated use (n = 21) was
      predicted by perceived ability to use, by self and partner satisfaction, by
      dislike of male condoms, and by previous diaphragm use. CONCLUSIONS: Gender
      sensitive cognitive-behavioral interventions can influence women to try the
      female condom. To increase long-term use, interventions may need to include self
      insertion practice and involvement of male partners.

PMID- 14600064
TI  - Evidence in support of foster care during acute refugee crises.
AB  - OBJECTIVES: The United Nations High Commissioner on Refugees (UNHCR) and United
      Nations Children's Fund (UNICEF) policy encourages foster care during refugee
      emergencies. We examined evidence to support this policy using data from the 1994
      Rwandan refugee crisis. METHODS: The association of weight gain and acute illness
      with family status (foster children vs children living with their biological
      families) was examined using latent growth curve and repeated measures logistic
      regression analysis. RESULTS: Weight gain for all children averaged 0.40 kg/month
      and was associated with child's age but not with family status, child's or
      caregiver's sex, caregiver's marital status, possession of blankets or plastic
      sheeting, severe malnutrition, month of enrollment, or acute illness. Illness was
      not more common among foster children than among children living with their
      biological families. CONCLUSIONS: This analysis supports the UNHCR/UNICEF
      recommendation of fostering for unaccompanied children during an acute refugee
      crisis.

PMID- 14600065
TI  - Trends in antimicrobial prescribing for bronchitis and upper respiratory
      infections among adults and children.
AB  - OBJECTIVES: This study examined antimicrobial prescribing patterns for adults and
      children with bronchitis or upper respiratory infections (URIs) before and after
      release of nationally disseminated pediatric practice recommendations. METHODS:
      Data from the 1993, 1995, 1997, and 1999 National Ambulatory Medical Care Survey
      were used to evaluate prescriptions for antimicrobials for URIs and bronchitis.
      RESULTS: From 1993 to 1999, the proportion of children receiving antimicrobials
      after visits for URIs and bronchitis decreased. However, the use of broad
      spectrum antimicrobials rose from 10.6% of bronchitis visits to 40.5%.
      Prescriptions of antimicrobials for adults with URIs or bronchitis showed a
      decrease between 1993 and 1999. CONCLUSIONS: Although antimicrobial prescribing
      for URIs and bronchitis has decreased for both children and adults, the
      prescribing of broad-spectrum antibiotics among children has shown a proportional
      rise.

PMID- 14600066
TI  - Regional patterns and correlates of substance use among young men who have sex
      with men in 7 US urban areas.
AB  - OBJECTIVES: We sought to characterize substance use patterns in young men who
      have sex with men (MSM) in 7 US urban areas and sociodemographic characteristics
      and history associated with such use. METHODS: We examined data collected from
      1994 through 1998 in a venue-based, cross-sectional survey. RESULTS: Among the
      3492 participants, 66% reported use of illicit drugs; 28%, use of 3 or more
      drugs; 29%, frequent drug use (once a week or more); and 4%, injection drug use.
      These practices were more common among participants who were White, self
      identified as bisexual or heterosexual, had run away, or had experienced forced
      sex. CONCLUSIONS: Effective drug prevention and treatment programs addressing
      local drug-use patterns and associated factors are urgently needed for young MSM,
      a population with a high rate of illicit drug use.

PMID- 14600067
TI  - Breaking the alliance: Defeating the tobacco industry's allies and enacting youth
      access restrictions in Massachusetts.
AB  - OBJECTIVES: We describe the tobacco industry's effort in Massachusetts to block
      the adoption of local regulations designed to reduce youth access to tobacco
      products. We also explain how state-funded tobacco control advocates overcame
      industry opposition. METHODS: We examined internal tobacco industry documents and
      records of local boards of health and conducted interviews with participants in
      local regulatory debates. RESULTS: The industry fought proposed regulations by
      working through a trade group, the New England Convenience Store Association.
      With industry direction and financing, the association's members argued against
      proposed regulations in local public hearings. However, these efforts failed
      because community-based advocates worked assiduously to cultivate support for the
      regulations among board of health members and local community organizations.
      CONCLUSIONS: Passage of youth access regulations by local boards of health in
      Massachusetts is attributed to ongoing state funding for local tobacco control
      initiatives, agreement on common policy goals among tobacco control advocates,
      and a strategy of persuading boards of health to adopt and enforce their own
      local regulations.

PMID- 14600068
TI  - Watering down the drinks: The moderating effect of college demographics on
      alcohol use of high-risk groups.
AB  - OBJECTIVES: This study examined whether colleges with larger enrollments of
      students from demographic groups with lower rates of binge drinking exert a
      moderating effect on students from groups with higher binge drinking rates.
      METHODS: The study analyzed data from 114 colleges included in the 1993, 1997,
      1999, and 2001 College Alcohol Study surveys. RESULTS: The binge drinking rates
      of White, male, and underage students were significantly lower in schools that
      had more minority, female, and older students. Students who do not binge drink in
      high school are more likely to start binge drinking at colleges with fewer
      minority and older students. CONCLUSIONS: Student-body composition and
      demographic diversity should be examined by colleges wishing to reduce their
      binge drinking problems.

PMID- 14600069
TI  - Funding public health: The public's willingness to pay for domestic violence
      prevention programming.
AB  - OBJECTIVES: The author investigated the willingness of the general public to pay
      for domestic violence prevention programs. METHODS: An experimental design was
      used in a telephone survey of 522 California adults. One of 11 funding methods
      and one of 4 dollar amounts were randomly assigned to each respondent. RESULTS:
      Most respondents (79.4%) reported support for domestic violence prevention
      programming. They were most willing to pay 5 US dollars or less via "user fees"
      (e.g., increased fines for batterers) and humanitarian "donations" (e.g., sales
      of special postage stamps). CONCLUSIONS: Health departments that want to increase
      their domestic violence prevention programming need to identify widely accepted
      methods by which funds can be raised. The methods used here can be applied to
      numerous public health activities and issues.

PMID- 14600070
TI  - Caregiving to children and grandchildren and risk of coronary heart disease in
      women.
AB  - OBJECTIVES: We examined the relationship between burden of providing care to non
      ill children and grandchildren and incidence of coronary heart disease (CHD)
      among women. METHODS: A prospective cohort study was conducted as part of the
      Nurses' Health Study among 54,412 women aged 46 to 71 years who were registered
      nurses. Women answered questions about their child care responsibilities.
      RESULTS: We documented 321 incident cases of CHD during 4 years of follow-up.
      Multivariate analyses showed that caring for non-ill children 21 hours or more
      per week and caring for non-ill grandchildren 9 hours or more per week (vs no
      caregiving) were associated with an increased risk of CHD (relative risks were
      1.59 and 1.55, respectively). CONCLUSIONS: High levels of care provision to
      grandchildren (and possibly children) may increase the risk of CHD among women.

PMID- 14600072
TI  - Adipose tissue triglyceride turnover, de novo lipogenesis, and cell proliferation
      in humans measured with 2H2O.
AB  - The turnover of adipose tissue components (lipids and cells) and the pathways of
      adipose lipid deposition have been difficult to measure in humans. We apply here
      a (2)H(2)O long-term labeling technique for concurrent measurement of adipose
      triglyceride (TG) turnover, cell (DNA) proliferation, and de novo lipogenesis
      (DNL). Healthy subjects drank (2)H(2)O (70 ml/day) for 5-9 wk. Subcutaneous
      adipose tissue aspirates were taken (gluteal, thigh, and flank depots). Deuterium
      incorporation into TG glycerol (representing all-source TG synthesis), TG
      palmitate (representing DNL, by mass isotopomer distribution analysis), and DNA
      (representing cell proliferation) was measured by gas chromatography-mass
      spectrometry. Subjects tolerated the protocol well, and body (2)H(2)O enrichments
      were stable. Mean TG-glycerol fractional synthesis was 0.12 (i.e., 12%) with a
      range of 0.03-0.32 after 5 wk and 0.20 (range 0.08-0.49) after 9 wk (TG half-life
      200-270 days). Label decay measurements 5-8 mo after discontinuing (2)H(2)O gave
      similar turnover estimates. Net lipolysis (TG turnover) was 50-60 g/day. DNL
      contribution to adipose-TG was 0.04 after 9 wk, representing approximately 20% of
      newly deposited TG. Cell proliferation was 0.10-0.17 after 9 wk (half-life 240
      425 days). In summary, long-term (2)H(2)O administration to human subjects allows
      measurement of the dynamics of adipose tissue components. Turnover of all
      elements is slow, and DNL contributes approximately 20% of new TG.

PMID- 14600071
TI  - Racial/ethnic differences in rates of depression among preretirement adults.
AB  - OBJECTIVES: We estimated racial/ethnic differences in rates of major depression
      and investigated possible mediators. METHODS: Depression prevalence rates among
      African American, Hispanic, and White adults were estimated from a population
      based national sample and adjusted for potential confounders. RESULTS: African
      Americans (odds ratio [OR] = 1.16, 95% confidence interval [CI] = 0.93, 1.44) and
      Hispanics (OR = 1.44, 95% CI = 1.02, 2.04) exhibited elevated rates of major
      depression relative to Whites. After control for confounders, Hispanics and
      Whites exhibited similar rates, and African Americans exhibited significantly
      lower rates than Whites. CONCLUSIONS: Major depression and factors associated
      with depression were more frequent among members of minority groups than among
      Whites. Elevated depression rates among minority individuals are largely
      associated with greater health burdens and lack of health insurance, factors
      amenable to public policy intervention.

PMID- 14600073
TI  - Additive effects of cortisol and growth hormone on regional and systemic
      lipolysis in humans.
AB  - Growth hormone (GH) and cortisol are important to ensure energy supplies during
      fasting and stress. In vitro experiments have raised the question whether GH and
      cortisol mutually potentiate lipolysis. In the present study, combined in vivo
      effects of GH and cortisol on adipose and muscle tissue were explored. Seven lean
      males were examined four times over 510 min. Microdialysis catheters were
      inserted in the vastus lateralis muscle and in the subcutaneous adipose tissue of
      the thigh and abdomen. A pancreatic-pituitary clamp was maintained with
      somatostatin infusion and replacement of GH, insulin, and glucagon at baseline
      levels. At t = 150 min, administration was performed of NaCl (I), a 2 microg.kg(
      1).min(-1) hydrocortisone infusion (II), a 200-microg bolus of GH (III), or a
      combination of II and III (IV). Systemic free fatty acid (FFA) turnover was
      estimated by [9,10-3H]palmitate appearance. Circulating levels of glucose,
      insulin, and glucagon were comparable in I-IV. GH levels were similar in I and II
      (0.50 +/- 0.08 microg/l, mean +/- SE). Peak levels during III and IV were
      approximately 9 microg/l. Cortisol levels rose to approximately 900 nmol/l in II
      and IV. Systemic (i.e., palmitate fluxes, s-FFA, s-glycerol) and regional
      (interstitial adipose tissue and skeletal muscle) markers of lipolysis increased
      in response to both II and III. In IV, they were higher and equal to the isolated
      additive effects of the two hormones. In conclusion, we find that GH and cortisol
      stimulate systemic and regional lipolysis independently and in an additive manner
      when coadministered. On the basis of previous studies, we speculate that the mode
      of action is mediated though different pathways.

PMID- 14600074
TI  - Treatment of type 2 diabetic db/db mice with a novel PPARgamma agonist improves
      cardiac metabolism but not contractile function.
AB  - Hearts from insulin-resistant type 2 diabetic db/db mice exhibit features of a
      diabetic cardiomyopathy with altered metabolism of exogenous substrates and
      reduced contractile performance. Therefore, the effect of chronic oral
      administration of 2-(2-(4-phenoxy-2-propylphenoxy)ethyl)indole-5-acetic acid
      (COOH), a novel ligand for peroxisome proliferator-activated receptor-gamma that
      produces insulin sensitization, to db/db mice (30 mg/kg for 6 wk) on cardiac
      function was assessed. COOH treatment reduced blood glucose from 27 mM in
      untreated db/db mice to a normal level of 10 mM. Insulin-stimulated glucose
      uptake was enhanced in cardiomyocytes from COOH-treated db/db hearts. Working
      perfused hearts from COOH-treated db/db mice demonstrated metabolic changes with
      enhanced glucose oxidation and decreased palmitate oxidation. However, COOH
      treatment did not improve contractile performance assessed with ex vivo perfused
      hearts and in vivo by echocardiography. The reduced outward K+ currents in
      diabetic cardiomyocytes were still attenuated after COOH. Metabolic changes in
      COOH-treated db/db hearts are most likely indirect, secondary to changes in
      supply of exogenous substrates in vivo and insulin sensitization.

PMID- 14600075
TI  - Transgenic complementation of leptin receptor deficiency. II. Increased leptin
      receptor transgene dose effects on obesity/diabetes and fertility/lactation in
      lepr-db/db mice.
AB  - We have generated mice that are homozygous for a leptin receptor transgene that
      is expressed exclusively in neurons (NSE-LEPR-B). We had previously shown that
      this transgene in the hemizygous state is effective in ameliorating almost all
      aspects of leptin receptor deficiency. Now, we show that the transgene, in the
      homozygous state, almost fully corrects the excess adiposity of LEPR-deficient
      (db/db) mice. Body composition analyses indicate that the transgene is able to
      restrain the massive increase in adiposity observed in LEPR-deficient mice.
      Examination of hypothalamic agouti gene-related peptide and proopiomelanocortin
      mRNA shows normalization of these leptin-regulated transcripts. Interestingly,
      despite normalization of circulating leptin concentrations by the transgene in
      the fed state, transgenic db3J/db mice did not show fasting-induced reductions of
      circulating leptin. Increased adiposity of the transgenic db/db mice at 4 wk of
      age, immediately postweaning, suggests that the transgene is less effective in
      correcting the preferential fat deposition caused by LEPR deficiency. We noted
      that the morphology of brown adipose tissue is nearly normal, concordant with the
      cold tolerance conferred by the transgene. Aspects of the diabetes phenotype are
      also corrected: glucose and insulin concentrations are nearly normal, and islet
      hyperplasia is greatly diminished. The transgene also corrects the infertility of
      db/db females and confers the ability to lactate sufficiently to nurse normal
      sized litters. Finally, the slightly increased adiposity and mild insulin
      resistance of transgenic db/db dams were not a contributory factor to the
      increased fat content of transgenic db/db male progeny.

PMID- 14600076
TI  - PPARgamma is not required for the inhibitory actions of PGJ2 on cytokine
      signaling in pancreatic beta-cells.
AB  - Peroxisome proliferator-activated receptor (PPAR)gamma agonists, such as 15-deoxy
      delta 12,14-prostaglandin J2 (PGJ2) and troglitazone, have been shown to elicit
      anti-inflammatory effects in pancreatic beta-cells that include inhibition of
      cytokine-stimulated inducible nitric oxide synthase (iNOS) gene expression and
      production of nitric oxide. In addition, these ligands impair IL-1-induced NF
      kappaB and MAPK as well as IFN-gamma-stimulated signal transducer and activator
      of transcription (STAT)1 activation in beta-cells. The purpose of this study was
      to determine if PPARgamma activation participates in the anti-inflammatory
      actions of PGJ2 in beta-cells. Pretreatment of RINm5F cells for 6 h with PGJ2
      results in inhibition of IL-1-stimulated IkappaB degradation and IFN-gamma
      stimulated STAT1 phosphorylation. Overexpression of a dominant-negative (dn)
      PPARgamma mutant or treatment with the PPARgamma antagonist GW-9662 does not
      modulate the inhibitory actions of PGJ2 on cytokine signaling in RINm5F cells.
      Although these agents fail to attenuate the inhibitory actions of PGJ2 on
      cytokine signaling, they do inhibit PGJ2-stimulated PPARgamma response element
      reporter activity. Consistent with the inability to attenuate the inhibitory
      actions of PGJ2 on cytokine signaling, neither dnPPARgamma nor GW-9662 prevents
      the inhibitory actions of PGJ2 on IL-1-stimulated iNOS gene expression or nitric
      oxide production by RINm5F cells. These findings support a PPARgamma-independent
      mechanism by which PPARgamma ligands impair cytokine signaling and iNOS
      expression by islets.

PMID- 14600077
TI  - Calcium homeostasis in rat cardiomyocytes during chronic hypoxia: a time course
      study.
AB  - The present study determined Ca2+ handling in the hearts of rats subjected to
      chronic hypoxia (CH). Spectrofluorometry was used to measure intracellular Ca2+
      concentration ([Ca2+]i) and its responses to electrical stimulation, caffeine,
      and isoproterenol in myocytes from the right ventricle of rats breathing 10%
      oxygen for 1, 3, 7, 14, 21, 28, and 56 days and age-matched controls. The protein
      expression of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) and its ryanodine
      receptor (RyR) were measured. The uptake of 45Ca2+ by SERCA, release by RyR, and
      extrusion by Na+/Ca2+ exchange (NCX) were determined. It was found that Ca2+
      homeostasis and Ca2+ responses to beta-adrenoceptor stimulation reached a new
      equilibrium after 4 wk of CH. Ca2+ content in the sarcoplasmic reticulum (SR) was
      reduced, but cytosolic Ca2+ remained unchanged after CH. Expression of SERCA and
      its Ca2+ uptake, Ca2+ release via RyR, and NCX activity were suppressed by CH.
      The results indicate impaired Ca2+ handling, which may be responsible for the
      attenuated Ca2+ responses to beta-adrenoceptor stimulation in CH.

PMID- 14600078
TI  - Ca2+ antagonist-insensitive coronary smooth muscle contraction involves
      activation of epsilon-protein kinase C-dependent pathway.
AB  - Certain angina and coronary artery disease forms do not respond to Ca2+ channel
      blockers, and a role for vasoactive eicosanoids such as PGF2alpha in Ca2+
      antagonist-insensitive coronary vasospasm is suggested; however, the signaling
      mechanisms are unclear. We investigated whether PGF2alpha-induced coronary smooth
      muscle contraction is Ca2+ antagonist insensitive and involves activation of a
      PKC-dependent pathway. We measured contraction in single porcine coronary artery
      smooth muscle cells and intracellular free Ca2+ concentration ([Ca2+]i) in fura 2
      loaded cells and examined cytosolic and particulate fractions for PKC activity
      and reactivity with isoform-specific PKC antibodies. In Hanks' solution (1 mM
      Ca2+), PGF2alpha (10-5 M) caused transient [Ca2+]i increase followed by
      maintained [Ca2+]i increase and 34% cell contraction. Ca2+ channel blockers
      verapamil and diltiazem (10-6 M) abolished maintained PGF2alpha-induced [Ca2+]i
      increase but only partially inhibited PGF2alpha-induced cell contraction to 17%.
      Verapamil-insensitive PGF2alpha contraction was inhibited by PKC inhibitors GF
      109203X, calphostin C, and epsilon-PKC V1-2. PGF2alpha caused Ca2+-dependent
      alpha-PKC and Ca2+-independent epsilon-PKC translocation from cytosolic to
      particulate fractions that was inhibited by calphostin C. Verapamil abolished
      PGF2alpha-induced alpha-but not epsilon-PKC translocation. PMA (10-6 M), a direct
      activator of PKC, caused 21% contraction with no significant [Ca2+]i increase and
      epsilon-PKC translocation that were inhibited by calphostin C but not verapamil.
      Membrane depolarization by 51 mM KCl, which stimulates Ca2+ influx, caused 36%
      cell contraction and [Ca2+]i increase that were inhibited by verapamil but not GF
      109203X or calphostin C and did not cause alpha- or epsilon-PKC translocation.
      Thus a significant component of PGF2alpha-induced contraction of coronary smooth
      muscle is Ca2+ antagonist insensitive, involves Ca2+-independent epsilon-PKC
      activation and translocation, and may represent a signaling mechanism of Ca2+
      antagonist-resistant coronary vasospasm.

PMID- 14600079
TI  - Effects of peroxynitrite on sarco/endoplasmic reticulum Ca2+ pump isoforms
      SERCA2b and SERCA3a.
AB  - Sarco(endo)plasmic reticulum Ca2+ (SERCA) pumps are important for cell signaling.
      Three different genes, SERCA1, 2, and 3, encode these pumps. Most tissues,
      including vascular smooth muscle, express a splice variant of SERCA2 (SERCA2b),
      whereas SERCA3a is widely distributed in tissues such as vascular endothelium,
      tracheal epithelium, mast cells, and lymphoid cells. SERCA2b protein is readily
      inactivated by peroxynitrite that may be formed during cardiac ischemia
      reperfusion or during immune response after infection. Here, we compared the
      peroxynitrite sensitivity of SERCA2b and SERCA3a by using microsomes prepared
      from HEK-293T cells overexpressing the pumps. We incubated the microsomes with
      different concentrations of peroxynitrite and determined Ca2+ uptake, Ca2+-Mg2+
      ATPase, Ca2+-dependent formation of acylphosphate intermediate, and protein
      mobility in Western blots. Ca2+ uptake, Ca2+-Mg2+-ATPase, and Ca2+-dependent
      formation of acylphosphate intermediate were inactivated for both SERCA2b and
      SERCA3a, but the latter was more resistant to the inactivation. Western blots
      showed that SERCA2b and SERCA3a proteins oligomerized after treatment with
      peroxynitrite, but each with a slightly different pattern. Compared with
      monomers, the oligomers may be less efficient in forming the acylphosphate
      intermediate and in conducting the remainder of the steps in the reaction cycle.
      We conclude that the resistance of SERCA3a to peroxynitrite may aid the cells
      expressing them in functioning during exposure to oxidative stress.

PMID- 14600080
TI  - Role of Ca2+-activated K+ channels in human erythrocyte apoptosis.
AB  - Exposure of erythrocytes to the Ca2+ ionophore ionomycin has recently been shown
      to induce cell shrinkage, cell membrane blebbing, and breakdown of
      phosphatidylserine asymmetry, all features typical of apoptosis of nucleated
      cells. Although breakdown of phosphatidylserine asymmetry is thought to result
      from activation of a Ca2+-sensitive scramblase, the mechanism and role of cell
      shrinkage have not been explored. The present study was performed to test whether
      ionomycin-induced activation of Ca2+-sensitive Gardos K+ channels and subsequent
      cell shrinkage participate in ionomycin-induced breakdown of phosphatidylserine
      asymmetry of human erythrocytes. According to on-cell patch-clamp experiments,
      ionomycin (1 microM) induces activation of inwardly rectifying K+-selective
      channels in the erythrocyte membrane. Fluorescence-activated cell sorter analysis
      reveals that ionomycin leads to a significant decrease of forward scatter,
      reflecting cell volume, an effect blunted by an increase of extracellular K+
      concentration to 25 mM and exposure to the Gardos K+ channel blockers
      charybdotoxin (230 nM) and clotrimazole (5 microM). As reflected by annexin
      binding, breakdown of phosphatidylserine asymmetry is triggered by ionomycin, an
      effect again blunted, but not abolished, by an increase of extracellular K+
      concentration and exposure to charybdotoxin (230 nM) and clotrimazole (5 microM).
      Similar to ionomycin, glucose depletion leads (within 55 h) to annexin binding of
      erythrocytes, an effect again partially reversed by an increase of extracellular
      K+ concentration and exposure to charybdotoxin. K-562 human erythroleukemia cells
      similarly respond to ionomycin with cell shrinkage and annexin binding, effects
      blunted by antisense, but not sense, oligonucleotides against the small
      conductance Ca2+-activated K+ channel isoform hSK4 (KCNN4). The experiments
      disclose a novel functional role of Ca2+-sensitive K+ channels in erythrocytes,
      i.e., their participation in regulation of erythrocyte apoptosis.

PMID- 14600081
TI  - Tomatoes or lycopene versus prostate cancer: is evolution anti-reductionist?

PMID- 14600083
TI  - Defining global health: who is responsible for the world's burden of disease?

PMID- 14600082
TI  - Playing the old piano: another tune for endocrine therapy?

PMID- 14600084
TI  - Stat bite: Causes of death in developed and developing countries.

PMID- 14600085
TI  - VA system a model for health care, experts say.

PMID- 14600088
TI  - Ewing's sarcoma: a miracle drug waiting to happen?

PMID- 14600090
TI  - Prostate carcinogenesis in N-methyl-N-nitrosourea (NMU)-testosterone-treated rats
      fed tomato powder, lycopene, or energy-restricted diets.
AB  - BACKGROUND: Consumption of tomato products or lycopene and energy restriction
      have been hypothesized to reduce the risk of human prostate cancer. We
      investigated the effects of these dietary variables in a rat model of prostate
      carcinogenesis. METHODS: Male rats (n = 194) treated with N-methyl-N-nitrosourea
      and testosterone to induce prostate cancer were fed diets containing whole tomato
      powder (13 mg lycopene/kg diet), lycopene beadlets (161 mg lycopene/kg diet), or
      control beadlets. Rats in each group were randomly assigned to either ad libitum
      feeding or 20% diet restriction. Differences between Kaplan-Meier survival curves
      for diet composition or restriction were tested with the log-rank test. Cox
      proportional hazards models were developed to examine the combined effect of diet
      composition and restriction on survival. Statistical tests were two-sided.
      RESULTS: Risk of death with prostate cancer was lower for rats fed the tomato
      powder diet than for rats fed control beadlets (hazard ratio [HR] = 0.74, 95%
      confidence interval [CI] = 0.59 to 0.93; P =.009). In contrast, prostate cancer
      specific mortality of the control and lycopene-fed rats was similar (P =.63). The
      proportions of rats dying with prostate cancer in the control, lycopene, and
      tomato powder groups were 80% (95% CI = 68% to 89%), 72% (95% CI = 60% to 83%),
      and 62% (95% CI = 48% to 75%), respectively. Rats in the diet-restricted group
      experienced longer prostate cancer-free survival than rats in the ad libitum-fed
      group (HR = 0.68, 95% CI = 0.49 to 0.96; P =.029). The proportion of rats that
      developed prostate cancer was 79% (95% CI = 69% to 86%) for ad libitum-fed rats
      and 65% (95% CI = 54% to 74%) for rats fed restricted diets. No interactions were
      observed between diet composition and dietary restriction. CONCLUSIONS:
      Consumption of tomato powder but not lycopene inhibited prostate carcinogenesis,
      suggesting that tomato products contain compounds in addition to lycopene that
      modify prostate carcinogenesis. Diet restriction also reduced the risk of
      prostate cancer. Tomato phytochemicals and diet restriction may act by
      independent mechanisms.

PMID- 14600091
TI  - Apoptotic action of 17beta-estradiol in raloxifene-resistant MCF-7 cells in vitro
      and in vivo.
AB  - BACKGROUND: Resistance to tamoxifen, a selective estrogen receptor modulator
      (SERM), involves changes that prevent apoptosis and enhance cell proliferation
      and survival. Paradoxically, estrogen treatment inhibits the growth of long-term
      tamoxifen-treated breast tumors. Because of the increasing use of raloxifene,
      another SERM, to prevent osteoporosis and potentially reduce breast cancer risk,
      some women will develop raloxifene-resistant breast cancer. We developed a
      raloxifene-resistant MCF-7 cell model (MCF-7/Ral) and investigated the nature of
      raloxifene-resistant breast cancer and its response to estradiol. METHODS:
      Raloxifene resistance and hormone responsiveness were assessed by proliferation
      assays and cell cycle analysis in parental MCF-7 and MCF-7/Ral cells. Nuclear
      factor kappaB (NF-kappaB) activity was investigated with a transient transfection
      assay. Apoptosis was investigated by annexin V staining, mRNA was measured by
      real-time polymerase chain reaction, and protein was measured by western
      blotting. Tumorigenesis was studied by injecting MCF-7 or MCF-7/Ral cells into
      ovariectomized athymic mice (10 per group) and monitoring tumor size weekly. All
      statistical tests were two-sided. RESULTS: Basal NF-kappaB activity was higher in
      MCF-7/Ral cells (1.6 U, 95% confidence interval [CI] = 1.2 to 2.0 U) than in MCF
      7 cells (0.8 U, 95% CI = 0.4 to 1.1 U; P =.004). When cultured with 1 microM
      raloxifene, MCF-7/Ral cells grew statistically significantly (P<.001) faster than
      MCF-7 cells. Estradiol treatment of MCF-7/Ral cells arrested cells in G(2)/M
      phase of the cell cycle, decreased NF-kappaB activity (0.2 U, 95% CI = 0.2 to 0.3
      U; P<.001), increased expression of Fas protein and mRNA (4.5-fold, 95% CI = 2.8-
      to 6.3-fold versus 0.5-fold, 95% CI = 0.3- to 0.8-fold for control treatment;
      P<.001), and induced apoptosis. Treatment with either raloxifene or tamoxifen
      stimulated MCF-7/Ral tumor growth, suggesting that such tumors were resistant to
      both drugs. When a 9-week raloxifene or tamoxifen treatment was followed by a 5
      week estradiol treatment, estradiol statistically significantly reduced the size
      of tumors stimulated by raloxifene or tamoxifen (at week 14, P =.004 for
      raloxifene and P<.001 for tamoxifen). CONCLUSIONS: Growth of raloxifene-resistant
      MCF-7/Ral cells in vitro and in vivo is repressed by estradiol treatment by a
      mechanism involving G2/M-phase arrest, decreased NF-kappaB activity, and
      increased Fas expression to induce apoptosis.

PMID- 14600092
TI  - Paradoxical action of fulvestrant in estradiol-induced regression of tamoxifen
      stimulated breast cancer.
AB  - BACKGROUND: Long-term tamoxifen treatment of breast cancer can result in
      tamoxifen-stimulated breast cancer, in which estrogen inhibits tumor growth after
      tamoxifen withdrawal. We investigated the molecular mechanism(s) of estradiol
      induced tumor regression by using an in vivo model of tamoxifen-stimulated human
      breast cancer. METHODS: Growth of parental estradiol-stimulated MCF-7E2 and long
      term tamoxifen-stimulated MCF-7TAMLT xenografts in athymic mice was measured
      during treatment with vehicle, estradiol, estradiol plus tamoxifen, tamoxifen
      alone, estradiol plus fulvestrant, or fulvestrant alone. Apoptosis was detected
      by the terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate
      nick-end labeling (TUNEL) assay. Protein expression was assessed by western blot
      analysis. mRNA expression was assessed by real-time reverse transcription
      polymerase chain reaction. All statistical tests were two-sided. RESULTS: MCF-7E2
      tumor growth was stimulated by estradiol (cross-sectional area at week 13 = 1.06
      cm2, 95% confidence interval [CI] = 0.82 to 1.30 cm2; P<.001) compared with
      control (0.06 cm2, 95%CI = -0.02 to 0.14 cm2), but tumor growth was inhibited by
      tamoxifen or fulvestrant. MCF-7TAMLT tumor growth was stimulated by tamoxifen)
      cross-sectional area at week 10 = 0.60 cm2, 95% CI = 0.50 to 0.70 cm2; P<.001)
      compared with control (0.02 cm2, 95% CI = 0.00 to 0.04 cm2). For MCF-7TAMLT
      tumors that were initially 0.35 cm2, estradiol-induced regression to 0.18 cm2
      (95% CI = 0.15 to 0.21 cm2; P<.001), and tamoxifen or estradiol plus fulvestrant
      enhanced tumor growth to 1.00 cm2 (95% CI = 0.88 to 1.22 cm2). Estradiol
      increased the number of apoptotic cells in tumors by 23% (95% CI = 20% to 26%;
      P<.001) compared with all other treatments, decreased estrogen receptor
      alpha(ERalpha) protein expression, increased the expression of Fas mRNA and
      protein, decreased the expression of HER2/neu mRNA and protein and nuclear factor
      kappaB (NF-kappaB) protein but did not affect Fas ligand protein expression
      compared with control. Paradoxically, fulvestrant reversed this effect and
      stimulated MCF-7TAMLT tumor growth apparently through ERalpha-mediated regulation
      of Fas, HER2/neu, and NF-kappaB. CONCLUSION: Physiologic levels of estradiol
      induced regression of tamoxifen-stimulated breast cancer tumors, apparently by
      inducing the death receptor Fas and suppressing the antiapoptotic/prosurvival
      factors NF-kappaB and HER2/neu.

PMID- 14600093
TI  - Extended follow-up of a cohort of british chemical workers exposed to
      formaldehyde.
AB  - BACKGROUND: Formaldehyde is mutagenic and, when inhaled at high concentrations,
      carcinogenic in rats. Some epidemiologic studies have linked occupational
      exposure to formaldehyde with cancers of the nose, nasopharynx, and lung, but the
      evidence for human carcinogenicity has been inconsistent and requires
      clarification. METHODS: We extended by 11 years the follow-up of an existing
      cohort of 14 014 men employed after 1937 at six British factories where
      formaldehyde was produced or used. Subjects had been identified from employment
      records, and their jobs had been classified for potential exposure to
      formaldehyde. Standardized mortality ratios (SMRs) were derived using the person
      years method and were compared with the expected numbers of deaths for the
      national population. RESULTS: During follow-up through December 31, 2000, 5185
      deaths were recorded, including two from sino-nasal cancer (2.3 expected) and one
      from nasopharyngeal cancer (2.0 expected). Relative to the national population,
      mortality from lung cancer was increased among those who worked with
      formaldehyde, particularly in men in the highest of four estimated exposure
      categories (>2 ppm) (SMR = 1.58, 95% confidence interval = 1.40 to 1.78), and the
      increase persisted after adjustment for local geographic variations in mortality
      (SMR = 1.28, 95% confidence interval = 1.13 to 1.44). However, there was a
      statistically nonsignificant decrease in the risk of death from lung cancer with
      duration of high exposure (P(trend) =.18), and this risk showed no trend with
      time since first high exposure (P(trend) =.99). CONCLUSIONS: The evidence for
      human carcinogenicity of formaldehyde remains unconvincing. Although a small
      effect on sino-nasal or nasopharyngeal cancer cannot be ruled out, a possible
      increase in the risk of lung cancer is a greater concern.

PMID- 14600094
TI  - Mortality from lymphohematopoietic malignancies among workers in formaldehyde
      industries.
AB  - BACKGROUND: Many U.S. factory workers are exposed to formaldehyde. Although
      increased risks for leukemia have been found in medical workers and other
      professionals exposed to formaldehyde, studies in industrial workers, who are
      thought to have higher exposures, have shown inconsistent associations. We
      extended follow-up of a cohort of industrial workers to evaluate the association
      between formaldehyde exposure and lymphohematopoietic cancers. METHODS: The
      cohort consisted of 25 619 workers (865 708 person-years) employed before January
      1, 1966, at one of 10 U.S. industrial plants and followed through December 31,
      1994. We analyzed formaldehyde exposure (peak exposure, average exposure
      intensity, cumulative exposure, and duration of exposure) and mortality from
      lymphohematopoietic malignancies using standardized mortality ratios and relative
      risks and 95% confidence intervals (CIs) based on Poisson regression. Statistical
      tests were two-sided. RESULTS: Among the cohort, there were 178 deaths from
      lymphohematopoietic malignancies. Relative risks for leukemia (69 deaths),
      particularly for myeloid leukemia (30 deaths), increased with formaldehyde
      exposure. Compared with workers exposed to low peak levels of formaldehyde (0.1
      1.9 ppm), relative risks for myeloid leukemia were 2.43 (95% CI = 0.81 to 7.25)
      and 3.46 (95% CI = 1.27 to 9.43) for workers exposed to peak levels of 2.0-3.9
      ppm and > or = 4.0 ppm, respectively (P(trend) =.009). Compared with workers
      exposed to low levels of average exposure intensity of formaldehyde (0.1-0.4
      ppm), workers exposed to 0.5-0.9 ppm and > or = 1.0 ppm average intensity had
      relative risks of 1.15 (95% CI = 0.41 to 3.23) and 2.49 (95% CI = 1.03 to 6.03),
      respectively (P(trend) =.088). The relative risk for leukemia was not associated
      with cumulative exposure but was weakly associated with duration of exposure.
      Relative risks for Hodgkin's disease also increased with formaldehyde exposure.
      CONCLUSIONS: Exposure to formaldehyde may cause leukemia, particularly myeloid
      leukemia, in humans. However, results from other investigations are mixed,
      suggesting caution in drawing definitive conclusions.

PMID- 14600095
TI  - Magnetic resonance spectroscopic pharmacodynamic markers of the heat shock
      protein 90 inhibitor 17-allylamino,17-demethoxygeldanamycin (17AAG) in human
      colon cancer models.
AB  - BACKGROUND: 17-allylamino,17-demethoxygeldanamycin (17AAG) is a novel anticancer
      drug that inhibits heat shock protein 90 (Hsp90), resulting in proteasomal
      degradation of several oncogenic proteins. We used phosphorus magnetic resonance
      spectroscopy (31P-MRS) to determine whether 17AAG treatment leads to alterations
      in phospholipids that could serve as pharmacodynamic markers for tumor response
      to 17AAG. METHODS: HCT116, HT29, and SW620 colon cancer cells were treated with
      17AAG, and extracts were examined by 31P-MRS. HT29 cells were also treated with
      the active metabolite of 17AAG, 17-amino,17-demethoxygeldanamycin (17AG), or the
      inactive 17AAG analog NSC683666. MF-1 nude mice carrying HT29 xenografts were
      examined using in vivo 31P-MRS before and after 17AAG treatment; xenograft tumor
      extracts were examined by 31P-MRS and proton MRS (1H-MRS). Hsp90 client protein
      expression was determined by using western blots. Two-tailed t tests were used to
      compare metabolite concentrations and ratios, and a Mann-Whitney U test was used
      to compare proportions. All statistical tests were two-sided. RESULTS: 17AAG
      treatment led to statistically significantly increased phosphocholine levels in
      all three cell lines (P =.02). 17AG treatment also increased phosphocholine
      levels in HT29 cells, whereas NSC683666 had no effect. The
      phosphomonoester/phosphodiester ratio was statistically significantly increased
      in the HT29 xenografts after 17AAG treatment relative to the pretreatment ratio
      (P =.02), whereas no statistically significant change was observed after vehicle
      treatment (P =.62). Statistically significant increases in phosphocholine,
      phosphoethanolamine, and valine levels were also observed in tumor extracts
      treated with 17AAG. CONCLUSIONS: Inhibition of Hsp90 by 17AAG resulted in altered
      phospholipid metabolism in cultured tumor cells and in tumor xenografts. The
      increases observed in phosphocholine and phosphomonoester levels suggest that
      these metabolites may have the potential to act as noninvasive pharmacodynamic
      markers for analyzing tumor response to treatment with 17AAG or other Hsp90
      inhibitors.

PMID- 14600098
TI  - Re: Role of body surface area in dosing of investigational anticancer agents in
      adults, 1991-2001.

PMID- 14600096
TI  - Quantitative GSTP1 methylation and the detection of prostate adenocarcinoma in
      sextant biopsies.
AB  - Hypermethylation of the 5' promoter region of the glutathione S-transferase pi
      gene (GSTP1) occurs at a very high frequency in prostate adenocarcinoma. We
      compared the results of blinded histologic review of sextant biopsy samples from
      72 excised prostates with those obtained using a quantitative methylation
      specific polymerase chain reaction assay (QMSP) for GSTP1. Formal surgical
      pathologic review of the resected prostates was used to determine the number of
      patients with (n = 61) and without (n = 11) prostate cancer. Histology alone
      detected prostate carcinoma with 64% sensitivity (95% confidence interval [CI] =
      51% to 76%) and 100% specificity (95% CI = 72% to 100%), whereas the combination
      of histology and GSTP1 QMSP at an assay threshold greater than 10 detected
      prostate carcinoma with 75% sensitivity (95% CI = 63% to 86%) and 100%
      specificity (95% CI = 72% to 100%), an 11% improvement (95% CI = 5% to 22%) in
      sensitivity over histology alone. The combination of histology and GSTP1 QMSP at
      an assay threshold greater than 5 detected prostate adenocarcinoma with 79%
      sensitivity (95% CI = 68% to 89%), a 15% improvement (95% CI = 7% to 26%) over
      histology alone. Thus, GSTP1 QMSP improved the sensitivity of histologic review
      of random needle biopsies for prostate cancer diagnosis. Further studies should
      determine whether detection of GSTP1 hypermethylation in a biopsy sample with
      normal histology indicates the need for an early repeat biopsy at the same site.

PMID- 14600099
TI  - Re: Personality and the risk of cancer.

PMID- 14600100
TI  - Re: Gynecologic surgeries and risk of ovarian cancer in women with BRCA1 and
      BRCA2 Ashkenazi founder mutations: an Israeli population-based case-control
      study.

PMID- 14600102
TI  - Rethinking the terms non-communicable disease and chronic disease.

PMID- 14600103
TI  - 100 years of poverty.

PMID- 14600104
TI  - Will the severe acute respiratory syndrome epidemic recur?

PMID- 14600105
TI  - Evidence based health promotion: recollections, reflections, and
      reconsiderations.

PMID- 14600106
TI  - Victoire Cappe--for social justice.

PMID- 14600107
TI  - Income inequality and health: multilevel analysis of Chilean communities.
AB  - STUDY OBJECTIVE: The evidence supporting the effect of income inequality on
      health has been largely observed in societies far more egalitarian than the US.
      This study examines the cross sectional multilevel associations between income
      inequality and self rated poor health in Chile; a society more unequal than the
      US. DESIGN: A multilevel statistical framework of 98 344 people nested within 61
      978 households nested within 285 communities nested within 13 regions. SETTING:
      The 2000 National Socioeconomic Characterization Survey (CASEN) data from Chile.
      PARTICIPANTS: Adults aged 18 and above. The outcome was a dichotomised self rated
      health (0 if very good, good or average; 1 if poor, or very poor). Individual
      level exposures included age, sex, ethnicity, marital status, education,
      employment status, type of health insurance, and household level exposures
      include income and residential setting (urban/rural). Community level exposures
      included the Gini coefficient and median income. MAIN RESULTS: Controlling for
      individual/household predictors, a significant gradient was observed between
      income and poor self rated health, with very poor most likely to report poor
      health (OR: 2.94) followed by poor (OR: 2.77), low (OR: 2.06), middle (OR: 1.73),
      high (OR: 1.38) as compared with the very high income earners. Controlling for
      household and community effects of income, a significant effect of community
      income inequality was observed (OR:1.22). CONCLUSIONS: Household income does not
      explain any of the between community differences; neither does it account for the
      effect of community income inequality on self rated health, with more unequal
      communities associated with a greater probability of reporting poor health.

PMID- 14600108
TI  - Work and health in a contemporary society: demands, control, and insecurity.
AB  - OBJECTIVE: To examine independent associations of job strain (high demands and
      low control) and job insecurity with mental and physical health outcomes. DESIGN:
      Cross sectional general population study conducted in 2000 using a self completed
      questionnaire. SETTING: Two adjoining cities in south east Australia. SUBJECTS:
      1188 employed professionals, aged 40-44 years, 55% (n = 655) male. MAIN OUTCOME
      MEASURES: Depression, anxiety, physical, and self rated health (SRH). RESULTS:
      Adverse job conditions were relatively prevalent as 23% of the sample reported
      high job strain, while 7.3% and 23% reported high and moderate job insecurity
      respectively. Associations between job conditions and health persisted after
      adjustment for gender, education, marital status, employment status, major life
      events, and negative affectivity (personality). When adjusted for job strain,
      high job insecurity was independently associated with a greater than threefold
      increase in odds for poor SRH, depression and anxiety (OR (95% confidence
      intervals) poor SRH: 3.72 (1.97 to 7.04) depression: 3.49 (1.90 to 6.41),
      anxiety: 3.29 (1.71 to 6.33)), and a twofold increase for physical health 2.19
      (1.21 to 3.95). High job strain also showed significant independent associations
      with depression: 2.54 (1.34 to.4.75) and anxiety: 3.15 (1.48 to 6.70).
      CONCLUSION: In this relatively privileged socioeconomic group, insecure
      employment and high job strain showed independent, consistent, and strong
      associations with physical and mental health. These adverse job conditions are on
      the increase, particularly insecure employment, and the influence of these two
      work conditions are an important focus for future public health research and
      their prevalence and impact should be examined in other occupations.

PMID- 14600109
TI  - Behind the mask. Journey through an epidemic: some observations of contrasting
      public health responses to SARS.
AB  - SARS has been called the first global epidemic of the 21st century and has been
      the cause of a massive and varied public health response in many countries of the
      world. This report describes observations made by two authors on a journey from
      Manchester in the United Kingdom to Chiang Mai in Thailand during the peak of
      global transmission. The public response to SARS, particularly characterised by
      the wearing of face masks, seemed to outstrip official guidance. Though of
      uncertain protective benefit, the wearing of masks may have contributed to the
      awareness of the collective and personal responsibility in combating infectious
      disease. Active and empowered involvement of the general public in implementing
      and cooperating with public health control measures supported by national and
      international authorities has clearly helped to bring SARS under control. The
      public health significance of such potent symbols as the face mask may be
      considered in strategies to tackle other emerging infections.

PMID- 14600110
TI  - The impact of community psychological responses on outbreak control for severe
      acute respiratory syndrome in Hong Kong.
AB  - OBJECTIVE: To examine the public's knowledge and perception of SARS and the
      extent to which various precautionary measures have been adopted. DESIGN: Cross
      sectional survey. SETTING: General population of Hong Kong at the height of the
      SARS outbreak (29 March to 6 April 2003). PARTICIPANTS: 1115 ethnic Chinese
      adults. MAIN RESULTS: Forty per cent did not recognise fomites as a possible mode
      of transmission whereas 55.1% believed that the infection could be transmitted
      airborne. A large proportion (30.1%) believed they were very or somewhat likely
      to contract SARS while only one quarter believed they were very likely to survive
      if they contracted the disease, benchmarked against an actual case fatality ratio
      of 2.8% at the time of the survey and 15%-20% according to current best
      estimates. Precautionary measures directed against person to person droplet
      spread were generally adopted by most while the prevention of transmission
      through fomites was not practised as frequently. Respondents with higher risk
      perceptions and a moderate level of anxiety were most likely to take
      comprehensive precautionary measures against the infection, as were older,
      female, more educated people as well as those with a positive contact history and
      SARS-like symptoms. CONCLUSIONS: The findings demonstrate that the promotion of
      protective personal health practices to interrupt the self sustaining
      transmission of the SARS virus in the community must take into account background
      perceptions of risk and anxiety levels of the public at large. Continuing public
      education about preventive measures should be targeted at the identified groups
      with low current uptake of precautions.

PMID- 14600111
TI  - Monitoring community responses to the SARS epidemic in Hong Kong: from day 10 to
      day 62.
AB  - STUDY OBJECTIVE: To report the evolution in perceptions and behaviours of the
      general public in response to the severe acute respiratory syndrome (SARS)
      epidemic in Hong Kong. DESIGN: Ten similar and sequential telephone surveys were
      conducted during outbreak of SARS, which are classified as belonging to the first
      and second phases of the epidemic. SETTING: Hong Kong, China. PARTICIPANTS: 1397
      Hong Kong residents between 18 and 60 years of age. MAIN OUTCOME MEASURES:
      Perceptions and behaviours to SARS and its prevention. RESULTS: Most of the
      respondents believed that SARS could be transmitted via direct body contact and
      droplets. About half of respondents believed that SARS was curable, which
      increased in the initial phase and decreased in the second phase. Perceived
      chance of infection was low (9%) but fear of infection in public places was high
      (48%). Perceived efficacy of hygiene measures (wearing a mask: 82%, hand washing:
      93%, and home disinfection: 75%) remained high in both phases and the perceived
      efficacy of avoiding crowded place, and using public transportation, etc,
      increased initially and decreased in the second phase. In parallel, use of the
      three hygiene measures increased significantly in the first phase and remained
      high for wearing a mask and washing hands in the second phase. Percentages of
      people avoiding crowded place and public transportation significantly increased
      initially and decreased in the second phase. CONCLUSION: SARS related perceptions
      and behaviours evolved rapidly during the epidemic and Hong Kong residents
      quickly adopted appropriate SARS prevention measures. Timely dissemination of
      information seems effective in public health crises management.

PMID- 14600112
TI  - Effect of social exclusion on the risk of teenage pregnancy: development of
      hypotheses using baseline data from a randomised trial of sex education.
AB  - STUDY OBJECTIVE: The UK government argues that "social exclusion" increases risk
      of teenage pregnancy and that educational factors may be dimensions of such
      exclusion. The evidence cited by the government is limited to reporting that
      socioeconomic disadvantage and educational attainment influence risk. Evidence
      regarding young people's attitude to school is not cited, and there is a lack of
      research concerning the UK. This paper develops hypotheses on the relation
      between socioeconomic and educational dimensions of social exclusion, and risk of
      teenage pregnancy, by examining whether dislike of school and socioeconomic
      disadvantage are associated with cognitive/behavioural risk measures among 13/14
      year olds in English schools. DESIGN: Analysis of data from the baseline survey
      of a study of sex education. SETTING AND PARTICIPANTS: 13/14 year old school
      students from south east England. MAIN RESULTS: The results indicate that
      socioeconomic disadvantage and dislike of school are associated with various risk
      factors, each with a different pattern. Those disliking school, despite having
      comparable knowledge to those liking school, were more likely to have sexual
      intercourse, expect sexual intercourse by age 16, and expect to be parents by the
      age of 20. For most associations, the crude odds ratios (ORs) and the ORs
      adjusted for the other exposure were similar, suggesting that inter-confounding
      between exposures was limited. CONCLUSIONS: It is hypothesised that in
      determining risk of teenage pregnancy, the two exposures are independent. Those
      disliking school might be at greater risk of teenage pregnancy because they are
      more likely to see teenage pregnancy as inevitable or positive.

PMID- 14600113
TI  - Impact of country of birth on hospital admission for women of childbearing age in
      Sweden: a five year follow up study.
AB  - STUDY OBJECTIVE: This study examines whether morbidity, defined as the first
      psychiatric hospital admission and the first somatic hospital admission, differs
      among subgroups of foreign born and second generation (that is, native born with
      at least one parent born abroad) women compared with Swedish born women (that is,
      with both parents native born) after adjusting for sociodemographic factors.
      DESIGN SETTING: In this follow up study the population consisted of 1 452 944
      women, of whom 369 771 have an immigrant background (including second generation
      immigrants), aged 20-45 years. The population of 31 December 1993 was followed up
      to 31 December 1998. Differences in risk (hazard ratio) between different groups
      of immigrant women were estimated, adjusting for age, marital status, number of
      children, and disposable income. MAIN RESULTS: All four groups of foreign born
      women had higher age adjusted risks (HRs varied from 1.44 to 1.67) for a first
      psychiatric hospital admission than Swedish born women. The risk decreased only
      marginally when the sociodemographic factors were taken into consideration.
      Additionally, second generation women also had a higher age adjusted risk (HR =
      1.42; CI = 1.37 to 1.48) than Swedish born women. The risk decreased only
      slightly in the main effect model. However, on analysing country of birth and
      first somatic hospital admissions, only non-European refugee women showed an
      increased age adjusted risk (HR = 1.26; CI = 1.24 to 1.29), which remained after
      adjusting for sociodemographic factors. CONCLUSIONS: Foreign born and second
      generation women of childbearing age had a higher risk than Swedish born women
      for a first psychiatric hospital admission. However, only non-European refugees
      were at higher risk of somatic hospital admissions.

PMID- 14600114
TI  - Crohn's disease, ulcerative colitis, and measles vaccine in an English
      population, 1979-1998.
AB  - STUDY OBJECTIVE: s: To study the hospitalised incidence of Crohn's disease (CD)
      and ulcerative colitis (UC) from 1979 to 1998; and to determine whether the
      introduction of the measles vaccination programme was associated with an increase
      in the young. DESIGN: Analysis of linked data on hospital admissions; a cohort
      analysis of the effect of the measles vaccination programme on the incidence of
      hospitalised CD and UC; and a comparison of these results with those from
      previous studies on the association between measles vaccine and CD or UC.
      SETTINGS: Southern England. SUBJECTS: People admitted to hospital with a main
      diagnosis of CD (1959 people) or UC (2018 people). MAIN RESULTS: Overall, the
      incidence of hospitalised CD showed no significant change over the 20 year
      period: the average change per year was 0.08% (95% confidence interval: -0.7% to
      0.9%). The relative risk associated with the measles vaccination programme was
      not significant (0.91: 0.5 to 1.4). The estimate differed significantly from the
      relative risk of 3.0 obtained in the original study reporting an association, but
      agreed with the combined estimate from three subsequent studies (0.95: 0.6 to
      1.5). The results for UC were similar. CONCLUSIONS: The incidence of hospitalised
      CD and UC remained stable over the 20 years, 1979 to 1998. Whatever caused the
      marked increases in CD and UC in the mid-20th century must itself have stabilised
      in this region. These results, together with those from other studies, provide
      strong evidence against measles vaccine causing CD or UC.

PMID- 14600116
TI  - Temperament in young adulthood and later mortality: prospective observational
      study.
AB  - STUDY OBJECTIVE: To determine the association between a clinician assessment of
      temperament in early adulthood and cause specific mortality. DESIGN: Prospective
      observational study. SETTING: Glasgow University. PARTICIPANTS: 9239 male former
      students aged 16-30 (mean 20.5) years who participated in an ongoing health
      survey from 1948-68. A physician recorded free text assessment of temperament,
      which seemed to capture aspects of personality (trait) and mental health (state),
      was coded into: stable, anxious, schizoid, hypomanic, odd, depressed, immature,
      hypochondriacal, unstable, and obsessive. Associations between temperament and
      mortality were investigated using Cox proportional hazards models. MAIN RESULTS:
      There were 878 deaths. Most students-8342 (90.3%)-were assessed as stable, the
      remaining 897 (9.7%) having at least one, and 103 (1.1%) having more than one,
      temperament type. The second most common temperament was anxiety, recorded in 520
      (5.6%) students. In multivariable analyses, having at least one temperament type
      was associated with increased all cause and stroke mortality, hazard ratios (95%
      confidence intervals): 1.23 (1.01 to 1.50) and 1.95 (1.06 to 3.59) respectively,
      compared with stable students. Students with more than one temperament type had
      higher risk of death from: all causes, 2.05 (1.36 to 3.09); stroke, 3.26 (1.01 to
      10.56); and cancer, 2.90 (1.62 to 5.20). Anxiety was positively associated with
      all cause and cancer mortality, respective hazard ratios: 1.36 (1.07 to 1.72) and
      1.51 (1.04 to 2.20). Men labelled hypomanic had increased cardiovascular
      mortality risk, 1.90 (1.05 to 3.44). CONCLUSIONS: Markers of early adult
      psychological distress are associated with increased mortality. Mechanisms
      underlying these associations require investigation.

PMID- 14600117
TI  - A different kind of contextual effect: geographical clustering of cocaine
      incidence in the USA.
AB  - STUDY OBJECTIVE: Outline the use of the pairwise odds ratio (PWOR) to quantify
      the extent to which a binary outcome clusters geographically. Quantify the extent
      to which first experience with cocaine is spatially correlated within US
      neighbourhoods and cities. Quantify geographical clustering of first experience
      with cocaine by neighbourhood context. DESIGN: Estimate the PWOR of incident
      cocaine experience at two levels (neighbourhood, city) and compare across years.
      Within years, estimate the PWOR by neighbourhood disadvantage and test for trend.
      SETTING: US National Household Survey on Drug Abuse. PARTICIPANTS: Civilian, non
      institutionalised household residents of the United States age 12 years and older
      interviewed in person during 1979, 1988, 1990, 1991, 1992, 1993. MAIN RESULTS:
      First experience with cocaine clusters within US neighbourhoods and cities. There
      is some evidence that the spatial correlation of first experience with cocaine
      increases with percentage of neighbourhood households living in poverty.
      CONCLUSIONS: The gradient in spatial correlation of incident cocaine experience
      by neighbourhood poverty level is consistent with current theories of
      concentrated disadvantage. The possibility that the direction of the poverty
      gradient might change over the course of a drug epidemic is discussed.

PMID- 14600118
TI  - Occupational mobility and risk factors in working men: selection, causality or
      both? Results from the GAZEL study.
AB  - OBJECTIVE: To explore the relation between risk factors (RF) and occupational
      mobility in working men. SETTING: 20 000 volunteers working at the French
      National Electricity and Gas Company (GAZEL cohort). PARTICIPANTS: Men aged 43 to
      53 years in 1992. DESIGN: Three designs were used for analysis. (1) The
      association between occupational mobility experienced before 1992 and RF reported
      at that date was analysed among 10 383 men. (2) The predictive role of RF on
      occupational mobility over 1992-1999 was studied in a subsample of 4715 men. (3)
      Reciprocally, occupational mobility in 1985-1992 was analysed in relation to RF
      changes over 1993-1999. MAIN OUTCOME MEASURES: Self reported smoking status,
      excessive alcohol consumption, arterial hypertension, and overweight.
      Occupational mobility defined by any upward transition between senior executives
      and professionals/middle executives/employees, and workers. RESULTS: (1) Cross
      sectionally, non-mobile men as their entry into the company had a higher risk of
      being smokers, excessive alcohol drinkers, and overweight in 1992 than mobile
      men. (2) Longitudinally, smokers and excessive alcohol drinkers in 1992 had a
      higher risk of non-mobility than, respectively, non-smokers and non-excessive
      alcohol drinkers. (3) Non-mobile men in 1985-1992 had a higher risk of becoming
      smokers, excessive alcohol drinkers, and hypertensive in 1993-1999 than upwardly
      mobile men. CONCLUSION: These results suggest a complex relation between RF and
      occupational mobility. A high level of RF, particularly health behaviours, might
      account for a selection process reducing upward occupational mobility. In turn, a
      lack of upward occupational mobility might be associated with an increased
      incidence of RF.

PMID- 14600119
TI  - Leisure activities and cognitive function in middle age: evidence from the
      Whitehall II study.
AB  - OBJECTIVES: To test the hypothesis of a positive association, independent of
      social position, between participation in leisure activities and cognitive
      function in middle age. The nature of this relation is explored by first
      classifying leisure activities as entailing high or low cognitive effort, and
      then classifying them as entailing individual or social activities. SETTING:
      London based office staff (Whitehall II study) in 20 civil service departments at
      baseline. METHODS: Data are from the fifth wave of data collection (phase 5) of a
      prospective cohort study, collected through clinical examination and a self
      administered questionnaire. Firstly, hierarchical multiple regression was used to
      examine age and socioeconomic status (SES) adjusted effect of each leisure
      activity on cognition. Then structural equation models were used to examine the
      effects of two categories of leisure activities-activities entailing high or low
      cognitive effort and social or individual activities. All analyses are cross
      sectional. RESULTS: There was an age and SES adjusted association between
      participation in leisure activities and cognitive function. More specifically,
      leisure activity entailing high cognitive effort or social interaction was
      associated with better cognitive ability. CONCLUSIONS: Participation in
      cognitively complex or social leisure activities has an independent association
      with adult cognition, suggesting that seeking mental stimulation may have a
      beneficial effect on cognition in middle age.

PMID- 14600121
TI  - Social epidemiology, intra-neighbourhood correlation, and generalised estimating
      equations.

PMID- 14600122
TI  - Sputum examination for early detection of lung cancer.
AB  - Conventional sputum cytology can be used for the detection of lung cancer, but
      has shown a low yield in prospective screening trials. This review focuses on the
      technical aspects relevant to the outcome of DNA and image analysis in sputum.
      Published articles are discussed in the light of the technical background. Recent
      developments in DNA analysis and nuclear image analysis show a clear potential to
      improve or refine diagnosis beyond that achieved with conventional sputum
      cytology examination. The challenge for future studies in DNA and nuclear
      analysis of sputum is to ensure high levels of quality control and to confirm
      these initial encouraging results.

PMID- 14600123
TI  - The Scotland and Newcastle epidemiological study of Hodgkin's disease: impact of
      histopathological review and EBV status on incidence estimates.
AB  - AIMS: The epidemiological and pathological features of Hodgkin lymphoma (HL) are
      complex. The Epstein-Barr virus (EBV) is consistently associated with a
      proportion of cases, and these cases are thought to represent a distinct
      aetiological subgroup of HL. The aim of the present analysis was to determine the
      age and sex specific incidence of EBV associated and non-associated HL, analysed
      separately, using data derived from a population based study-the Scotland and
      Newcastle epidemiological study of Hodgkin's disease (SNEHD). This study also
      provided a unique opportunity to evaluate accuracy in the current diagnosis and
      classification of HL. METHODS: SNEHD analysed consecutive cases of HL diagnosed
      in the study area between 1993 and 1997. Diagnostic biopsy material was
      retrieved, EBV status of tumours was determined, and histological review was
      performed. RESULTS: In total, 622 cases were eligible for the study, and EBV
      studies and histopathological review were performed on biopsy material from 537
      and 549 cases, respectively. Accuracy in the overall diagnosis of HL and
      classification of nodular sclerosis HL was good, but diagnosis of HL in the
      elderly and classification of other subtypes was less reliable. One third of
      classic HL cases were EBV associated, and age specific incidence curves for EBV
      associated and non-associated cases were distinct. CONCLUSIONS: Comparison of age
      specific incidence curves for EBV associated and non-associated HL supports the
      hypothesis that these are two distinct aetiological entities. Accuracy in the
      diagnosis of HL is generally good, but certain subgroups of cases continue to
      present diagnostic difficulties.

PMID- 14600124
TI  - Serum laminin and collagen IV in inflammatory bowel disease.
AB  - BACKGROUND: / AIMS: Laminin and collagen IV have been proposed as extracellular
      matrix serum markers. Because fibrosis is a major complication of inflammatory
      bowel disease, serum concentrations of laminin and collagen IV were measured in
      patients with ulcerative colitis (UC) and Crohn's disease (CD) and compared with
      inflammatory and healthy controls. METHODS: Laminin and collagen IV serum
      concentrations were measured in 170 patients with inflammatory bowel disease (86
      UC and 84 CD), in 23 patients with other causes of intestinal inflammation, and
      in 80 matched healthy controls using commercially available enzyme linked
      immunosorbent assays. Laminin and collagen IV concentrations were correlated with
      disease activity, type, localisation, and treatment. RESULTS: Mean (SD) serum
      laminin concentrations were 281.0 (110.1) ng/ml in patients with UC, 275.6
      (106.7) ng/ml in patients with CD, 192.0 (17.8) ng/ml in healthy controls, and
      198.5 (32.5) ng/ml in inflammatory controls. Mean (SD) serum collagen IV
      concentrations were 72.8 (22.9) ng/ml in patients with UC, 71.0 (18.2) in
      patients with CD, 79.8 (12.2) ng/ml in healthy controls, and 88.9 (24.6) ng/ml in
      inflammatory controls. There was a significant difference among the four groups
      (p < 0.0001) for both markers. There was a strong correlation between serum
      laminin, but not collagen IV, and disease activity in both diseases. No
      significant association was found between these markers and disease localisation
      or disease type. CONCLUSIONS: Serum concentrations of laminin are increased,
      whereas serum concentrations of collagen IV are decreased, in patients with
      inflammatory bowel disease. They may be useful surrogate markers for sustained
      inflammation and tissue remodelling.

PMID- 14600125
TI  - Fine needle aspiration cytology in the diagnosis of uncommon types of lymphoma.
AB  - AIMS: Fine needle aspiration (FNA) cytology is an accepted means of diagnosing
      and typing common forms of lymphoma, particularly small lymphocytic lymphoma,
      follicular lymphoma, and large B cell lymphoma. However, its usefulness for
      diagnosing less common forms of lymphoma is not clearly established and this
      study was designed to examine this. METHODS: The study reviewed the FNAs of
      suspected lymphomas collected over a period of approximately five years. RESULTS:
      FNA samples were available for 138 definite lymphomas; most were common forms of
      B cell lymphoma. However, there was also one Burkitt lymphoma (BL), two Burkitt
      like large B cell lymphomas, 15 classic Hodgkin lymphomas (HLs), two nodular
      lymphocyte predominant Hodgkin lymphomas, four mantle cell lymphomas, two
      mediastinal (thymic) large B cell lymphomas (MLBCLs), 11 peripheral T cell
      lymphomas (PTCLs), and five T cell rich large B cell lymphomas (TCRLBCLs).
      CONCLUSIONS: FNA diagnosis of BL was possible with immunoflow cytometry (IFC),
      cell block immunohistochemistry (IHC), and cell block fluorescent in situ
      hybridisation for c-myc alteration. It was difficult to make a definite diagnosis
      of HL and MLBCL on FNA alone. Both tend to be sclerotic tumours and FNA tends to
      yield scanty neoplastic cells. The FNA diagnosis of PTCL depended on cell block
      IHC; IFC was not usually useful. TCRLBCL did not show light chain restriction on
      IFC of FNA samples, probably because of frequent reactive B cells in the tumour.
      Thus, HL, MLBCL, and TCRLBCL are often difficult to diagnose accurately on FNA
      cytology, even when using IFC and cell block IHC.

PMID- 14600126
TI  - Low grade malignant peripheral nerve sheath tumour: varied cytological and
      histological patterns.
AB  - BACKGROUND: A small number of malignant peripheral nerve sheath tumours (MPNSTs)
      are low grade, and the nature of these low grade tumours has never been
      systematically assessed. AIMS: To describe the clinicopathological,
      immunohistochemical, and ultrastructural features of low grade MPNST and to
      discuss the main differential diagnoses. METHODS: Four cases of low grade MPNST
      were studied, including one coexistent with neurofibromatosis type 1. The tumours
      were analysed with respect to nuclear atypia, cellularity, nuclear enlargement,
      hyperchromasia, mitotic rate, and necrosis. Immunohistochemistry was performed by
      standard techniques, and an ultrastructural study was performed on one tumour.
      RESULTS: The ages of the patients ranged from 32 to 72 years (mean, 58). Two were
      male and two were female. Three tumours occurred in the deep tissue, including
      one in the retroperitoneum, and one was located in the dermal and subcutaneous
      tissue. The maximum diameters of the tumours ranged from 3.5 to 8.0 cm.
      Microscopically, all tumours showed moderate hypercellularity, an increased
      nuclear to cytoplasmic ratio, and hyperchromasia, but exhibited varied growth
      patterns, including those that were atypical neurofibroma-like, low grade
      fibromyxoid sarcoma-like, low grade epithelioid, and haemangiopericytoma-like.
      All tumours showed immunoreactivity for S-100 protein and vimentin. CONCLUSIONS:
      These findings suggest that careful clinical and histological evaluation, along
      with S-100 protein immunostaining, are essential for the accurate diagnosis of
      low grade MPNST.

PMID- 14600127
TI  - Prognostic relevance of rosette-like features in osteosarcoma.
AB  - AIMS: To clarify the prognostic relevance of rosette-like features and other
      clinicopathological and immunohistochemical variables in patients with
      osteosarcoma. METHODS: Clinicopathological and immunohistochemical variables were
      analysed in 131 patients with non-metastatic high grade conventional
      osteosarcoma, with particular attention to the prognostic impact of rosette-like
      features. RESULTS: Rosette-like features were present in 18 (14%) cases. Rosette
      like features were significantly associated with the osteoblastic subtype,
      numerous osteoclast-like giant cells, moderate pleomorphism, frequent
      haemangiopericytoma-like vascular patterns, epithelioid cytological features,
      positive immunoreactivity for epithelial membrane antigen and CD56, and negative
      staining for cytokeratin. In a multivariate analysis, rosette-like features
      (relative risk (RR), 3.8), a poor chemotherapy effect (RR, 2.9), and a tumour
      size of 10 cm or more (RR, 2.8) were identified as unfavourable prognostic
      factors. CONCLUSIONS: Rosette-like features can easily be identified from routine
      histological slides and the relative risk in patients with non-metastatic,
      conventional osteosarcoma is as high as other well known prognostic factors,
      including large size and poor chemotherapy effect.

PMID- 14600128
TI  - The nodular form of hepatic tuberculosis: a review with five additional new
      cases.
AB  - BACKGROUND: Tuberculosis presenting as an isolated liver tumour, without active
      pulmonary or miliary tuberculosis, or other clinical evidence of tuberculosis, is
      distinctly rare. A greater awareness of this rare clinical entity may prevent
      needless surgical intervention. AIMS: To help characterise this distinctly rare
      presentation of tuberculosis, five new cases are presented, together with a
      review of the world literature. The clinical, laboratory, radiological, and
      pathological features of these patients are described. METHODS: Polymerase chain
      reaction (PCR) assay of the liver tissue was carried out in all cases to confirm
      an aetiological diagnosis of Mycobacterium tuberculosis infection. RESULTS: All
      five patients (44-71 years old; two women, three men) underwent surgery, and had
      a preoperative diagnosis of malignant hepatic neoplasm and a postoperative
      histological diagnosis of chronic granulomatous inflammation, suggestive of
      tuberculosis. None of them had a known previous history of tuberculosis. All of
      them were positive for M tuberculosis by PCR analysis of the liver tissue.
      CONCLUSIONS: This report illustrates the difficulty in reaching a correct
      preoperative diagnosis. It is usually unsuspected and confused with primary or
      metastatic carcinoma of the liver, especially when it coexists with other
      malignancies. A high index of suspicion is required for diagnosis, which can be
      made only by histological and bacteriological studies, and PCR analysis.

PMID- 14600129
TI  - Parasite detection in patients with post kala-azar dermal leishmaniasis in India:
      a comparison between molecular and immunological methods.
AB  - AIMS: To evaluate the sensitivity and specificity of serological,
      immunohistochemical, and molecular methods in the diagnosis of post kala-azar
      dermal leishmaniasis (PKDL). METHODS: Twenty five patients with confirmed PKDL
      and 25 controls were included in the study. G2D10, a monoclonal antibody against
      Leishmania, was used for the immunohistochemical (IHC) staining of lesion
      sections to visualise anti-Leishmania donovani antibodies. The diagnostic
      usefulness of IHC was compared with enzyme linked immunosorbent assay (ELISA)
      with a recombinant (rk39) antigen, and a species specific polymerase chain
      reaction (PCR) assay, amplifying a kinetoplast minicircle DNA sequence. RESULTS:
      IHC detected 22 of 25 PKDL cases, giving a sensitivity of 88%. The diagnostic
      sensitivity of both the ELISA and PCR tests was higher (96%). All of the 25
      controls examined were negative in PCR, indicating 100% specificity of the test,
      whereas ELISA showed 96% specificity. CONCLUSIONS: IHC with G2D10 significantly
      enhances the sensitivity of detection of PKDL over routine haematoxylin and eosin
      staining. ELISA with a recombinant antigen is an economical and practical assay.
      PCR is the most sensitive and specific diagnostic method for PKDL. The tests
      described would facilitate the recognition of patients with PKDL, enabling timely
      treatment, which would contribute greatly to the control of kala-azar.

PMID- 14600130
TI  - Evaluation of the IRIS 939 UDx flow microscope as a screening system for urinary
      tract infection.
AB  - AIMS: To evaluate the IRIS flow microscope for the examination of urine specimens
      and to compare its performance with that of manual methods; in addition, to
      assess its usefulness as a screening system for the detection of significant
      bacteriuria in a routine clinical laboratory. METHODS: The IRIS system was
      compared with manual quantitative microscopy for the detection of formed elements
      and with a variety of culture methods to detect urinary tract infection. RESULTS:
      The IRIS had a higher sensitivity for the detection of clinically significant
      formed elements than did manual methods, and using a combination of bacterial and
      white cell counts produced a sensitivity and specificity of 94.9% and 54.4%,
      respectively, for predicting positive significant growth, with a 98.5% predictive
      value for a negative result. Approximately 50% of specimens could be reported as
      negative on the day of receipt using the screening algorithm. CONCLUSIONS: The
      sensitivity and specificity of the IRIS is equivalent to that of other automated
      screening systems and would remove the need for manual microscopy for most
      specimens. The system was easy to operate and is a useful addition to the methods
      currently available for the examination of urine specimens.

PMID- 14600131
TI  - Hepatic granulomas: a 10 year single centre experience.
AB  - BACKGROUND: Epithelioid granulomas have been reported in 2-15% of unselected
      liver biopsies, with numerous underlying aetiologies described. However, all UK
      series were reported before identification of hepatitis C virus (HCV). AIM: To
      evaluate the current aetiologies of hepatic granulomas and to assess the
      prognosis for the "idiopathic" group, in which all investigations for a
      recognised cause were negative or normal. METHODS: A retrospective review of
      patient case notes between 1991 and 2001; all patients who had a liver biopsy at
      Glasgow Royal Infirmary revealing epithelioid granulomas had their case notes and
      liver biopsies reviewed and a standard proforma completed. RESULTS: Over the
      study period, 1662 liver biopsies were performed. Hepatic granulomas were found
      in 63. Of those identified, 47 were female, with a mean age of 42 years (range,
      17-81). Underlying aetiologies were as follows: primary biliary cirrhosis (PBC;
      23.8%), sarcoidosis (11.1%), idiopathic (11.1%), drug induced (9.5%), HCV (9.5%),
      PBC/autoimmune hepatitis (AIH) overlap (6.3%), Hodgkin lymphoma (6.3%), AIH
      (4.8%), tuberculosis (4.8%), resolving biliary obstruction (3.2%), and other
      single miscellaneous causes (9.5%). Of the seven patients with idiopathic hepatic
      granulomas, one was lost to follow up, one died of stroke, and the remaining five
      were well with no liver related morbidity at a mean follow up of 6.2 years.
      CONCLUSIONS: The aetiology of hepatic granulomas is broad ranging, with HCV an
      important cause in this population. Despite extensive investigations, a 10-15% of
      patients still had "idiopathic" hepatic granulomas. However, the prognosis for
      this last group appears to be excellent.

PMID- 14600132
TI  - Angiopoietin switching regulates angiogenesis and progression of human
      hepatocellular carcinoma.
AB  - AIM: Angiopoietin 1 (Ang-1) and its antagonist, angiopoietin 2 (Ang-2), are novel
      ligands that regulate the Tie2 receptor. The Ang-2 gene is upregulated in the
      hypervascular type of human hepatocellular carcinoma (HCC). To gain a better
      understanding of the role of the Ang-Tie2 system in HCC the expression of these
      genes was investigated in a series of human HCCs. METHODS: The expression of the
      angiopoietin and Tie2 proteins was investigated in nine normal liver tissues and
      52 surgically resected HCCs. In addition, the effects of hypoxic stimuli on Ang
      1, Ang-2, vascular endothelial growth factor (VEGF), and erythropoietin (EPO)
      expression was investigated in Hep3B cells. RESULTS: Ang-1, rather than Ang-2,
      was more frequently expressed in the normal liver. Ang-1 was expressed in 68% of
      HCCs, whereas Ang-2 was expressed in 81%, and was significantly higher in poorly
      differentiated HCCs characterised by high vascularity (p = 0.02), and in tumours
      with a peliotic change (p = 0.02). Strong expression of Tie2 was seen in tumour
      vessels in accordance with Ang-2 expression. In Hep3B cells, hypoxic stimuli
      upregulated VEGF and EPO, but not Ang-1 or Ang-2. CONCLUSIONS: These data support
      the evidence that the reversal of Ang-1 and Ang-2 expression plays an important
      role in the angiogenic and dedifferentiation processes in HCC. The hypoxic
      stimuli were not responsible for Ang-2 upregulation, unlike that of VEGF, in
      human HCC cells.

PMID- 14600133
TI  - Unreliability of triglyceride measurement to predict turbidity induced
      interference.
AB  - Lipaemic specimens are a common problem in clinical chemistry. Most laboratories
      will measure the concentration of triglycerides and then decide whether the
      analytical result is valid or not. There is a poor association between the
      concentration of triglycerides and an objective assessment of turbidity for
      visually turbid specimens. Extrapolation of triglyceride concentrations derived
      from the use of intravenous emulsions to visually turbid specimens found in
      clinical practice will overestimate the turbidity induced interference in assays
      (non-turbid interferences are probably the same). The evaluation of turbidity
      induced interference needs to be standardised using objective assessments of
      turbidity.

PMID- 14600134
TI  - Core needle biopsy in male breast lesions.
AB  - AIMS: To describe results of needle core biopsies of the male breast. METHODS:
      Needle core biopsies from male breasts and corresponding histological follow up
      data were retrieved from pathology computer files. For those biopsies with no
      histological follow up data, the nationwide pathology computer files were
      consulted. RESULTS: Twenty six core biopsies of male breasts were performed from
      1993 until the end of 2002. All patients had unilateral lesions and were between
      20 and 88 years old. In seven patients, core biopsy results were confirmed in the
      excision specimen. In one patient, the core biopsy diagnosis of cancer was
      confirmed in another hospital. In 17 patients with a benign core biopsy that was
      not excised in one of the hospitals served by this laboratory, the nationwide
      pathology computer files did not retrieve a missed malignancy. One patient with
      cancer in a core biopsy did not receive surgery because of old age. Core biopsy
      or aspiration cytology was not used in six of 19 men with cancer. CONCLUSIONS:
      Core biopsy of the male breast is a reliable preoperative diagnostic procedure,
      which should be used more often because it can help to avoid unnecessary surgery
      and in planning surgery for cancer.

PMID- 14600135
TI  - Pulmonary tumour microembolism clinically mimicking alveolitis.
AB  - A 56 year old man with previously unsuspected recurrence of squamous cell
      carcinoma of the oesophagus presented with dyspnoea. Bronchoscopy and computed
      tomography suggested bronchopneumonic changes with an infectious cause. He
      suffered a rapidly deteriorating course and died despite active treatment,
      including antibiotics and mechanical ventilation. Necropsy revealed a florid
      pulmonary tumour microembolism mimicking alveolitis. No bronchopneumonia was
      seen. The emboli arose from loosely attached tumour vegetations in the tricuspid
      valve. In a patient with known malignancy, tumour microembolism should be
      considered as an uncommon cause of rapid respiratory failure, refractory to
      antibiotic treatment.

PMID- 14600136
TI  - Inflammatory pseudotumour associated with chronic persistent Eikenella corrodens
      infection: a case report and brief review.
AB  - Inflammatory pseudotumour is an uncommon mass forming lesion, representing the
      histological expression of an infective or reactive/reparative process
      (pseudotumour) in most cases, and a bona fide neoplasm (for example, inflammatory
      myofibroblastic tumour) in a minority of cases. This report describes the case of
      an inflammatory pseudotumour with a pathology that unveiled proliferative CD68
      positive and actin negative spindle shaped cells, with a mild mixed inflammatory
      infiltrate, and a culture that yielded an uncommon fastidious bacillus, Eikenella
      corrodens. The clinical course was indolent but protracted, with insidious
      progression to multifocal non-contiguous lesions, involving the lungs, liver,
      spleen, left kidney, and deep neck tissue, all of which responded to medical
      treatment with appropriate antibiotics. It is of paramount importance that
      clinicians search for an infective cause of an inflammatory pseudotumour, to
      ensure appropriate treatment.

PMID- 14600137
TI  - Chorioamnionitis caused by Serratia marcescens in a non-immunocompromised host.
AB  - A 26 year old pregnant woman with antithrombin III deficiency developed recurrent
      septicaemia with Serratia marcescens. In spite of the administration of
      antibiotics, high grade fever persisted. She subsequently manifested lower
      abdominal pain, and spontaneous abortion occurred. After the abortion, she became
      completely afebrile. The amnion was turbid, and microscopic examination of the
      placenta showed haemorrhage and massive infiltration of neutrophils, suggestive
      of infectious chorioamnionitis. Pulsed field gel electrophoresis showed that
      isolates from the blood, urine, and vaginal discharge were genetically identical.
      Intravenous pyelography revealed that she had a bilateral completed double
      ureter. It was thought that a urinary tract anomaly caused infection with S
      marcescens, and the pathogen spread to the chorioamnion via the bloodstream. This
      is the first report of chorioamnionitis caused by S marcescens in a non
      immunocompromised host. In addition, these findings indicate that the
      chorioamnion can serve as a site for persistent infection in normal pregnancies.

PMID- 14600138
TI  - Association of acute parvovirus B19 infection with new onset of acute
      lymphoblastic and myeloblastic leukaemia.
AB  - AIMS: To investigate the association of acute parvovirus B19 infection with new
      onset of acute lymphoblastic and myeloblastic leukaemia. METHODS: Cerebrospinal
      fluid (CSF) samples from patients with acute myelogenous leukaemia (AML) at
      diagnosis (n = 2) and acute lymphoblastic leukaemia (ALL) at diagnosis (n = 14)
      were analysed for parvovirus B19 DNA by means of nested polymerase chain
      reaction. In addition, samples from patients with benign intracranial
      hypertension (BIH) (n = 10) and hydrocephalus (n = 13) were tested as controls.
      RESULTS: Four leukaemia cases were positive-common ALL (n = 2), null cell ALL (n
      =1), and M7 AML (n = 1)-whereas all controls were negative (Yates corrected
      chi(2) value, 3.97; p = 0.046; odds ratio, 16.92; confidence interval, 1.03 to
      77.18). All four patients were significantly anaemic, but none was encephalitic
      or had evidence of central nervous system leukaemia. In three of these patients,
      serum tumour necrosis alpha, interferon gamma, interleukin 6, granulocyte
      macrophage colony stimulating factor (range, 34.93-3800.06 pg/ml), and macrophage
      chemoattractant protein 1 were detectable. All of these four patients carried at
      least one of the HLA-DRB1 alleles, which have been associated with symptomatic
      parvovirus B19 infection. CONCLUSION: Erythroid suppression and immune cell
      proliferation are both associated with B19 infection and may also be important in
      the pathogenesis of acute leukaemia.

PMID- 14600139
TI  - Massive haemoptysis after living donor liver transplantation.
AB  - A 27 year old man with hereditary haemorrhagic telangiectasia who developed
      progressive liver dysfunction underwent living related right lobe
      transplantation. Pulmonary arteriography did not reveal arteriovenous
      malformation or abnormal intrapulmonary venous channels. The postoperative course
      was characterised by persistent hypoxaemia and respiratory failure developed. On
      day 6, a massive haemoptysis developed and the patient died shortly thereafter.
      The native liver showed a nodular pseudocirrhotic transformation, with highly
      dilated and irregularly interconnected vein-like or arterial-like structures in
      the fibrous septa. Pathological examination of both lungs showed irregular
      thickening of the wall of the arteries, secondary to eccentric and/or concentric
      myointimal hyperplasia. This case suggests that massive haemoptysis can develop
      even when arteriovenous malformations are undetectable by pulmonary
      arteriography, and it questions the role and the appropriateness of living donor
      liver transplantation in high risk patients.

PMID- 14600140
TI  - Corticosteroids as adjunctive treatment in Austrian's syndrome (pneumococcal
      endocarditis, meningitis, and pneumonia): report of two cases and review of the
      literature.
AB  - This report describes two cases of Osler's triad of pneumonia, meningitis, and
      endocarditis, as a result of Streptococcus pneumoniae infection, also called
      Austrian's syndrome. In the first patient, a 51 year old non-alcoholic man, the
      aortic valve was affected and needed to be replaced in an emergency operation.
      The mitral valve was affected in a 70 year old woman without underlying disease,
      who only benefited from medical treatment. Both patients received
      corticosteroids, either dexamethasone followed by low doses of hydrocortisone and
      fludrocortisone, or only hydrocortisone and fludrocortisone, at the onset of the
      illness, and their outcome was favourable. These case reports focus on the
      presentation, prognosis, and therapeutic options for this severe syndrome.

PMID- 14600141
TI  - An immunodiagnostic method for the detection of Shiga-like toxigenic Escherichia
      coli in faeces.

PMID- 14600142
TI  - Recurrent urachal adenocarcinoma.

PMID- 14600143
TI  - Results of measurement of urine osmolality and sodium in the evaluation of severe
      hyponatraemia.

PMID- 14600144
TI  - Cartilage in bone marrow biopsy and purple granular deposits in the biopsy touch.

PMID- 14600145
TI  - Preservation of base-line hemodynamic function and loss of inducible
      cardioprotection in adult mice lacking protein kinase C epsilon.
AB  - Signaling pathways involving protein kinase C isozymes are modulators of
      cardiovascular development and response to injury. Protein kinase C epsilon
      activation in cardiac myocytes reduces necrosis caused by coronary artery
      disease. However, it is unclear whether protein kinase C epsilon function is
      required for normal cardiac development or inducible protection against oxidative
      stress. Protein kinase C delta activation is also observed during cardiac
      preconditioning. However, its role as a promoter or inhibitor of injury is
      controversial. We examined hearts from protein kinase C epsilon knock-out mice
      under physiological conditions and during acute ischemia reperfusion. Null-mutant
      and wild-type mice displayed equivalent base-line morphology and hemodynamic
      function. Targeted disruption of the protein kinase C epsilon gene blocked
      cardioprotection caused by ischemic preconditioning and alpha(1)-adrenergic
      receptor stimulation. Protein kinase C delta activation increased in protein
      kinase C epsilon knock-out myocytes without altering resistance to injury. These
      observations support protein kinase C epsilon activation as an essential
      component of cardioprotective signaling. Our results favor protein kinase C delta
      activation as a mediator of normal growth. This study advances the understanding
      of cellular mechanisms responsible for preservation of myocardial integrity as
      potential targets for prevention and treatment of ischemic heart disease.

PMID- 14600146
TI  - C/EBP-delta induction by gp130 signaling. Role in transition to myelin gene
      expressing phenotype in a melanoma cell line model.
AB  - Expression of genes encoding structural myelin proteins marks the inception of
      the myelinating Schwann cell (SC) phenotype. Earlier embryonic SC as well as
      adult non-myelinating SC produce the intermediate filament glial fibrillary acid
      protein (GFAP), which disappears from the myelinating SC. We previously observed
      that triggering of the gp130 receptor system by the IL6RIL6 ligand, comprising
      interleukin-6 (IL-6) fused to the soluble IL-6 receptor, induces myelin gene
      expression in rat embryonic dorsal root ganglia (DRG) cultures as well as in the
      murine melanoma cell line B16/F10.9. Study of target genes regulated by IL6RIL6
      indicates a strong and selective induction of the transcriptional regulator C/EBP
      delta in DRG cultures and in the F10.9 cell line. As shown here, silencing of
      C/EBP-delta mRNA and protein expression by introduction of small interference RNA
      producing plasmids in the F10.9 cells prevented the induction of myelin protein
      zero (P0) and myelin basic protein (MBP) mRNAs by IL6RIL6. Doxycycline-regulated
      overexpression of C/EBP-delta was sufficient to induce accumulation of P0 and MBP
      mRNAs, the effect being selective, because C/EBP-delta did not affect several
      other genes strongly regulated by IL6RIL6. Interestingly, GFAP was inhibited by
      C/EBP-delta overexpression, leading to a modulation of the ratio between myelin
      gene products versus GFAP and suggesting that C/EBP-delta plays a role in the
      switch to a myelinating phenotype. The down-regulation of Pax3, also typical of
      the transition to myelinating cells, was observed after C/EBP-delta expression in
      correlation to P0 induction and to decrease of melanogenesis and cell growth. In
      cultures of dissociated cells of embryonic rat DRG, where we knocked-down the
      C/EBP-delta mRNA, we found an inhibition of P0 mRNA induction by IL6RIL6, showing
      that the role of C/EBP-delta on this myelin gene is not unique to the melanoma
      system.

PMID- 14600147
TI  - Constitutive activation and uncoupling of the atrial natriuretic peptide receptor
      by mutations at the dimer interface. Role of the dimer structure in signalling.
AB  - The crystal packing of the extracellular hormone binding domain of the atrial
      natriuretic peptide (ANP) receptor contains two possible dimer pairs, the head-to
      head (hh) and tail-to-tail (tt) dimer pairs associated through the membrane
      distal and membrane-proximal subdomains, respectively. The tt-dimer structure has
      been proposed previously (van den Akker, F., Zhang, X., Miyagi, M., Huo, X.,
      Misono, K. S., and Yee, V. C. (2000) Nature 406, 101-104). However, no direct
      evidence is available to identify the physiological dimer form. Here we report
      site-directed mutagenesis studies of residues at the two alternative dimer
      interfaces in the full-length receptor expressed on COS cells. The Trp74 to Arg
      mutation (W74R) or D71R at the hh-dimer interface caused partial constitutive
      guanylate cyclase activation, whereas mutation F96D or H99D caused receptor
      uncoupling. In contrast, mutation Y196D or L225D at the tt-interface had no such
      effect. His99 modification at the hh-dimer interface by ethoxyformic anhydride
      abolished ANP binding. These results suggest that the hh-dimer represents the
      physiological structure. Recently, we determined the crystal structure of ANPR
      complexed with ANP and proposed a hormone-induced rotation mechanism mediating
      transmembrane signaling (H. Ogawa, Y. Qiu, C. M. Ogata, and K. S. Misono,
      submitted for publication). The observed effects of mutations are consistent with
      the ANP-induced structural change identified from the crystal structures with and
      without ANP and support the proposed rotation mechanism for ANP receptor
      signaling.

PMID- 14600148
TI  - Cells previously desensitized to type 1 interferons display different mechanisms
      of activation of stat-dependent gene expression from naive cells.
AB  - Over the past decade, a wealth of knowledge has been obtained concerning the
      mechanisms by which interferons (IFNs) and other cytokines activate or down
      regulate immediate early genes via the Jak/Stat pathway. In contrast, little
      information is available on interferon-activated gene expression in naive cells
      compared with cells that have been desensitized and subsequently resensitized to
      the actions of these cytokines. In naive cells, the ISG54 gene is activated via
      IFN beta-stimulated formation of ISGF3, a heterotrimeric DNA binding complex
      consisting of p48 (IRF9) and tyrosine-phosphorylated Stat1 and Stat2. In
      contrast, in previously desensitized cells IFN beta weakly stimulates the
      assembly of an ISGF3-like complex that lacks Stat1, even though ISG54 mRNA
      induction is the same as in naive cells. The lack of Stat1 tyrosine
      phosphorylation and DNA binding is due to increased activity of a protein
      tyrosine phosphatase. In cells that do not express the tyrosine phosphatase Tc
      PTP, the rate of Stat1 dephosphorylation is the same in naive and previously
      desensitized cells. These results implicate Tc-PTP in a novel role in the
      regulation of type 1 interferon-stimulated gene expression.

PMID- 14600149
TI  - BACE1 suppression by RNA interference in primary cortical neurons.
AB  - Extracellular deposition of amyloid-beta (Abeta) aggregates in the brain
      represents one of the histopathological hallmarks of Alzheimer's disease (AD).
      Abeta peptides are generated from proteolysis of the amyloid precursor proteins
      (APPs) by beta- and gamma-secretases. Beta-secretase (BACE1) is a type I integral
      membrane glycoprotein that can cleave APP first to generate C-terminal 99- or 89
      amino acid membrane-bound fragments containing the N terminus of Abeta peptides
      (betaCTF). As BACE1 cleavage is an essential step for Abeta generation, it is
      proposed as a key therapeutic target for treating AD. In this study, we show that
      small interfering RNA (siRNA) specifically targeted to BACE1 can suppress BACE1
      (but not BACE2) protein expression in different cell systems. Furthermore, BACE1
      siRNA reduced APP betaCTF and Abeta production in primary cortical neurons
      derived from both wild-type and transgenic mice harboring the Swedish APP mutant.
      The subcellular distribution of APP and presenilin-1 did not appear to differ in
      BACE1 suppressed cells. Importantly, pretreating neurons with BACE1 siRNA reduced
      the neurotoxicity induced by H2O2 oxidative stress. Our results indicate that
      BACE1 siRNA specifically impacts on beta-cleavage of APP and may be a potential
      therapeutic approach for treating AD.

PMID- 14600150
TI  - Pemphigus vulgaris IgG and methylprednisolone exhibit reciprocal effects on
      keratinocytes.
AB  - Pemphigus vulgaris (PV) is a life-threatening autoimmune disease of skin adhesion
      associated with IgG autoantibodies against keratinocytes (KC). Treatment of PV
      with systemic corticosteroids is life-saving, but the mechanism of the
      therapeutic action has not been fully understood. We have developed an animal
      model that demonstrates that methylprednisolone (MP) can block PV IgG-induced
      acantholysis, decreasing the extent of keratinocyte detachment in the epidermis
      of 3-5-day-old nude mice from 77.5 +/- 0.6 to 24.1 +/- 1.5% (p < 0.05). We
      hypothesized that in addition to immunosuppression, MP may exhibit direct anti
      acantholytic effects in epidermis, and we compared the effects of PV IgG and MP
      on KC. The use of DNA microarray showed that PV IgG down-regulated and MP up
      regulated expression of the genes encoding keratinocyte adhesion molecules,
      antigen-processing proteins, regulators of cell cycle and apoptosis,
      differentiation markers, Na+,K+-ATPase, protein kinases and phosphatases, and
      serine proteases and their inhibitors. Overall, PV IgG decreased transcription of
      198 genes and increased transcription of 31 genes. MP decreased transcription of
      14 genes and increased transcription of 818 genes. Specific effects of PV IgG and
      MP on keratinocyte adhesion molecules were further investigated by Western blot
      and immunofluorescence assays. By immunoblotting, MP increased the protein levels
      of E-cadherin and desmogleins 1 and 3 by 300, 180, and 40%, respectively.
      Specific staining of KC for E-cadherin and desmogleins 1 and 3 increased by 235,
      228, and 148%, respectively. In addition, PV IgG increased the level of
      phosphorylation of E-cadherin by 42%, beta-catenin by 37%, gamma-catenin by 136%,
      and desmoglein 3 by 300%, whereas pretreatment with 0.25 mm MP abolished
      phosphorylation of these adhesion molecules. These results suggested that
      therapeutic effects of MP in PV include both the up-regulated synthesis and post
      translational modification of the keratinocyte adhesion molecules.

PMID- 14600152
TI  - Functional cooperation between interleukin-17 and tumor necrosis factor-alpha is
      mediated by CCAAT/enhancer-binding protein family members.
AB  - Interleukin (IL)-17 is a recently described cytokine involved in the
      amplification of inflammatory responses and pathologies. A hallmark feature of IL
      17 is its ability to induce expression of other cytokines and chemokines. In
      addition, IL-17 potently synergizes with tumor necrosis factor-alpha (TNFalpha)
      to up-regulate expression of many target genes, particularly IL-6. Despite the
      many observations of IL-17 signaling synergy observed to date, little is known
      about the molecular mechanisms that underlie this phenomenon. In the osteoblastic
      cell line MC-3T3, we have found that IL-17 and TNFalpha exhibit potent synergy in
      mediating IL-6 secretion. Here, we show that at least part of the functional
      cooperation between IL-17 and TNFalpha occurs at the level of IL-6 gene
      transcription. Both the NF-kappaB and CCAAT/enhancer-binding protein (C/EBP; NF
      IL6) sites in the IL-6 promoter are important for cooperative gene expression,
      but NF-kappaB does not appear to be the direct target of the combined signal.
      Microarray analysis using the Affymetrix mouse MG-U74v2 chip identified
      C/EBPdelta as another gene target of combined IL-17- and TNFalpha-induced
      signaling. Because C/EBP family members are known to control IL-6, we examined
      whether enhanced C/EBPdelta expression is involved in the cooperative up
      regulation of IL-6 by IL-17 and TNFalpha. Accordingly, we show that C/EBPdelta
      (or the related transcription factor C/EBPbeta) is essential for expression of IL
      6. Moreover, overexpression of C/EBPdelta (and, to a lesser extent, C/EBPbeta)
      could substitute for the IL-17 signal at the level of IL-6 transcription. Thus,
      C/EBP family members, particularly C/EBPdelta, appear to be important for the
      functional cooperation between IL-17 and TNFalpha.

PMID- 14600151
TI  - Characterization of CA XIII, a novel member of the carbonic anhydrase isozyme
      family.
AB  - The carbonic anhydrase (CA) gene family has been reported to consist of at least
      11 enzymatically active members and a few inactive homologous proteins. Recent
      analyses of human and mouse databases provided evidence that human and mouse
      genomes contain genes for still another novel CA isozyme hereby named CA XIII. In
      the present study, we modeled the structure of human CA XIII. This model revealed
      a globular molecule with high structural similarity to cytosolic isozymes, CA I,
      II, and III. Recombinant mouse CA XIII showed catalytic activity similar to those
      of mitochondrial CA V and cytosolic CA I, with k(cat)/K(m) of 4.3 x 10(7) m(-1)
      s(-1), and k(cat) of 8.3 x 10(4) s(-1). It is very susceptible to inhibition by
      sulfonamide and anionic inhibitors, with inhibition constants of 17 nm for
      acetazolamide, a clinically used sulfonamide, and of 0.25 microm, for cyanate,
      respectively. Using panels of cDNAs we evaluated human and mouse CA13 gene
      expression in a number of different tissues. In human tissues, positive signals
      were identified in the thymus, small intestine, spleen, prostate, ovary, colon,
      and testis. In mouse, positive tissues included the spleen, lung, kidney, heart,
      brain, skeletal muscle, and testis. We also investigated the cellular and
      subcellular localization of CA XIII in human and mouse tissues using an antibody
      raised against a polypeptide of 14 amino acids common for both human and mouse
      orthologues. Immunohistochemical staining showed a unique and widespread
      distribution pattern for CA XIII compared with the other cytosolic CA isozymes.
      In conclusion, the predicted amino acid sequence, structural model, distribution,
      and activity data suggest that CA XIII represents a novel enzyme, which may play
      important physiological roles in several organs.

PMID- 14600153
TI  - Nitric oxide induces hypoxia-inducible factor 1 activation that is dependent on
      MAPK and phosphatidylinositol 3-kinase signaling.
AB  - Hypoxia-inducible factor-1 (HIF-1) is a master regulator of cellular adaptive
      responses to hypoxia. Levels of the HIF-1alpha subunit increase under hypoxic
      conditions. Exposure of cells to certain nitric oxide (NO) donors also induces
      HIF-1alpha expression under nonhypoxic conditions. We demonstrate that exposure
      of cells to the NO donor NOC18 or S-nitrosoglutathione induces HIF-1alpha
      expression and transcriptional activity. In contrast to hypoxia, NOC18 did not
      inhibit HIF-1alpha hydroxylation, ubiquitination, and degradation, indicating an
      effect on HIF-1alpha protein synthesis that was confirmed by pulse labeling
      studies. NOC18 stimulation of HIF-1alpha protein and HIF-1-dependent gene
      expression was blocked by treating cells with an inhibitor of the
      phosphatidylinositol 3-kinase or MAPK-signaling pathway. These inhibitors also
      blocked NOC18-induced phosphorylation of the translational regulatory proteins 4E
      BP1, p70 S6 kinase, and eIF-4E, thus providing a mechanism for the modulation of
      HIF-1alpha protein synthesis. In addition, expression of a dominant-negative form
      of Ras significantly suppressed HIF-1 activation by NOC18. We conclude that the
      NO donor NOC18 induces HIF-1alpha synthesis under conditions of NO formation
      during normoxia and that hydroxylation of HIF-1alpha is not regulated by NOC18.

PMID- 14600154
TI  - Response of human pulmonary epithelial cells to lipopolysaccharide involves Toll
      like receptor 4 (TLR4)-dependent signaling pathways: evidence for an
      intracellular compartmentalization of TLR4.
AB  - Pulmonary epithelial cells are continuously exposed to microbial challenges as a
      result of breathing. It is recognized that immune myeloid cells express Toll-like
      receptors (TLRs), which play a major role in detecting microbes and initiating
      innate immune responses. In contrast, little is known concerning the expression
      of TLR in pulmonary epithelial cells per se, their distribution within the cell,
      their function, and the signaling pathways involved. In this work, we
      demonstrated by reverse transcription-PCR and/or immunoblot that TLR4 and the
      accessory molecule MD-2 are constitutively expressed in distinct human alveolar
      and bronchial epithelial cells. We further characterized by flow cytometry,
      biotinylation/precipitation, and confocal microscopy the intracellular
      localization of TLR4 in these cells. Despite this intracellular
      compartmentalization of TLR4, pulmonary epithelial cells were responsive to the
      TLR4 activator lipopolysaccharide (LPS), a potent Gram-negative bacteria
      associated molecular pattern. Using respiratory epithelial cells isolated from
      TLR4 knock-out and wild type mice, we demonstrated that TLR4 is the actual
      activating receptor for LPS in these cells. Furthermore we showed that this cell
      response to LPS involves a signaling complex including the kinases interleukin-1
      receptor-associated kinase (IRAK), p38, Jnk, and ERK1/2. Moreover, using vectors
      expressing dominant-negative forms of MyD88 and TRAF6, we established that LPS
      induced activation of respiratory epithelial cells is largely dependent on TLR4
      signaling intermediates. Altogether these data demonstrate that TLR4 is a key
      element in the response of pulmonary epithelial cells to molecules derived from
      Gram-negative bacteria. The intracellular localization of TLR4 in lung epithelia
      is expected to play an important role in the prevention of the development of
      chronic inflammatory disease.

PMID- 14600155
TI  - The proton/amino acid cotransporter PAT2 is expressed in neurons with a different
      subcellular localization than its paralog PAT1.
AB  - The new member of the mammalian amino acid/auxin permease family, PAT2, has been
      cloned recently and represents an electrogenic proton/amino acid symporter. PAT2
      and its paralog, PAT1/LYAAT-1, are transporters for small amino acids such as
      glycine, alanine, and proline. Our immunodetection studies revealed that the PAT2
      protein is expressed in spinal cord and brain. It is found in neuronal cell
      bodies in the anterior horn in spinal cord and in brain stem, cerebellum,
      hippocampus, hypothalamus, rhinencephalon, cerebral cortex, and olfactory bulb in
      the brain. PAT2 is expressed in neurons positive for the N-methyl-d-aspartate
      subtype glutamate receptor subunit NR1. PAT2 is not found in lysosomes, unlike
      its paralog PAT1, but is present in the endoplasmic reticulum and recycling
      endosomes in neurons. PAT2 has a high external proton affinity causing half
      maximal transport activation already at a pH of 8.3, suggesting that its activity
      is most likely not altered by physiological pH changes. Transport of amino acids
      by PAT2 activity is dependent on membrane potential and can occur
      bidirectionally; membrane depolarization causes net glycine outward currents. Our
      data suggest that PAT2 contributes to neuronal transport and sequestration of
      amino acids such as glycine, alanine, and/or proline, whereby the transport
      direction is dependent on the sum of the driving forces such as substrate
      concentration, pH gradient, and membrane potential.

PMID- 14600156
TI  - ERK is regulated by sodium-proton exchanger in rat aortic vascular smooth muscle
      cells.
AB  - The purposes of this study were to test 1) the relationship between two widely
      studied mitogenic effector pathways, and 2) the hypothesis that sodium-proton
      exchanger type 1 (NHE-1) is a regulator of extracellular signal-regulated protein
      kinase (ERK) activation in rat aortic smooth muscle (RASM) cells. Angiotensin II
      (Ang II) and 5-hydroxytryptamine (5-HT) stimulated both ERK and NHE-1 activities,
      with activation of NHE-1 preceding that of ERK. The concentration-response curves
      for 5-HT and Ang II were superimposable for both processes. Inhibition of NHE-1
      with pharmacological agents or by isotonic replacement of sodium in the perfusate
      with choline or tetramethylammonium greatly attenuated ERK activation by 5-HT or
      Ang II. Similar maneuvers significantly attenuated 5-HT- or Ang II-mediated
      activation of MEK and Ras but not transphosphorylation of the epidermal growth
      factor (EGF) receptor. EGF receptor blockade attenuated ERK activation, but not
      NHE-1 activation by 5-HT and Ang II, suggesting that the EGF receptor and NHE-1
      work in parallel to stimulate ERK activity in RASM cells, converging distal to
      the EGF receptor but at or above the level of Ras in the Ras-MEK-ERK pathway.
      Receptor-independent activation of NHE-1 by acute acid loading of RASM cells
      resulted in the rapid phosphorylation of ERK, which could be blocked by
      pharmacological inhibitors of NHE-1 or by isotonic replacement of sodium, closely
      linking the proton transport function of NHE-1 to ERK activation. These studies
      identify NHE as a new regulator of ERK activity in RASM cells.

PMID- 14600157
TI  - Fas-associated factor-1 inhibits nuclear factor-kappaB (NF-kappaB) activity by
      interfering with nuclear translocation of the RelA (p65) subunit of NF-kappaB.
AB  - Fas-associated factor-1 (FAF1) is a Fas-binding pro-apoptotic protein that is a
      component of the death-inducing signaling complex in Fas-mediated apoptosis.
      Here, we show that FAF1 is involved in negative regulation of NF-kappaB
      activation. Overexpression of FAF1 decreased the basal level of NF-kappaB
      activity in 293 cells. NF-kappaB activation induced by tumor necrosis factor
      (TNF)-alpha, interleukin-1beta, and lipopolysaccharide was also inhibited by FAF1
      overexpression. Moreover, FAF1 suppressed NF-kappaB activation induced by
      transducers of diverse NF-kappaB-activating signals such as TNF receptor
      associated factor-2 and -6, MEKK1, and IkappaB kinase-beta as well as NF-kappaB
      p65, one of the end point molecules in the NF-kappaB activation pathway,
      suggesting that NF-kappaB p65 might be a target molecule upon which FAF1 acts.
      Subsequent study disclosed that FAF1 physically interacts with NF-kappaB p65 and
      that the binding domain of FAF1 is the death effector domain (DED)-interacting
      domain (amino acids 181-381), where DEDs of the Fas-associated death domain
      protein and caspase-8 interact. The NF-kappaB activity-modulating potential of
      FAF1 was also mapped to the DED-interacting domain. Finally, overexpression of
      FAF1 prevented translocation of NF-kappaB p65 into the nucleus and decreased its
      DNA-binding activity upon TNFalpha treatment. This study presents a novel
      function of FAF1, in addition to the previously known function as a component of
      the Fas death-inducing signaling complex, i.e. NF-kappaB activity suppressor by
      cytoplasmic retention of NF-kappaB p65 via physical interaction.

PMID- 14600158
TI  - A failure of transforming growth factor-beta1 negative regulation maintains
      sustained NF-kappaB activation in gut inflammation.
AB  - Immunologically mediated tissue damage in the gut is associated with increased
      production of proinflammatory cytokines, which activate the transcription factor
      NF-kappaB in a variety of different cell types. The mechanisms/factors that
      negatively regulate NF-kappaB in the human gut and the pathways leading to the
      sustained NF-kappaB activation in gut inflammation remain to be identified.
      Pretreatment of normal human intestinal lamina propria mononuclear cells (LPMC)
      with transforming growth factor-beta1 (TGF-beta1) resulted in a marked
      suppression of TNF-alpha-induced NF-kappaB p65 accumulation in the nucleus, NF
      kappaB binding DNA activity, and NF-kappaB-dependent gene activation. TGF-beta1
      also increased IkappaBalpha transcripts and protein in normal LPMC. In marked
      contrast, treatment of LPMC from patients with inflammatory bowel disease with
      TGF-beta1 did not reduce TNF-induced NF-kappaB activation due to the
      overexpression of Smad7. Indeed inhibiting Smad7 by specific antisense
      oligonucleotides increased IkappaBalpha expression and reduced NF-kappaB p65
      accumulation in the nucleus. This effect was due to endogenous TGF-beta1. TGF
      beta1 directly stimulated IkappaBalpha promoter transcriptional activity in gut
      fibroblasts in vitro, and overexpression of Smad7 blocked this effect. These data
      show that TGF-beta1 is a negative regulator of NF-kappaB activation in the gut
      and that Smad7 maintains high NF-kappaB activity in gut inflammation by blocking
      TGF-beta1 signaling.

PMID- 14600159
TI  - Snake venom vascular endothelial growth factors (VEGFs) exhibit potent activity
      through their specific recognition of KDR (VEGF receptor 2).
AB  - Vascular endothelial growth factor (VEGF165) exhibits multiple effects via the
      activation of two distinct endothelial receptor tyrosine kinases: Flt-1 (fms-like
      tyrosine kinase-1) and KDR (kinase insert domain-containing receptor). KDR shows
      strong ligand-dependent tyrosine phosphorylation in comparison with Flt-1 and
      mainly mediates the mitogenic, angiogenic, and permeability-enhancing effects of
      VEGF165. Here we show the isolation of two VEGFs from viper venoms and the
      characterization of their unique biological properties. Snake venom VEGFs
      strongly stimulated proliferation of vascular endothelial cells in vitro.
      Interestingly, the maximum activities were almost twice that of VEGF165. They
      also induced strong hypotension on rat arterial blood pressure compared with
      VEGF165 in vivo. A receptor binding assay revealed that snake venom VEGFs bound
      to KDR-IgG with high affinity (Kd = approximately 0.1 nm) as well as to VEGF165
      but did not interact with Flt-1, Flt-4, or neuropilin-1 at all. Our data clearly
      indicate that snake venom VEGFs act through the specific activation of KDR and
      show potent effects. Snake venom VEGFs are a highly specific ligand to KDR and
      form a new group of the VEGF family.

PMID- 14600160
TI  - Skeletal muscle unweighting: spaceflight and ground-based models.
AB  - Long-term manned spaceflight requires that flight crews be exposed to extended
      periods of unweighting of antigravity skeletal muscles. This exposure will result
      in adaptations in these muscles that have the potential to debilitate crew
      members on return to increased gravity environments. Therefore, the development
      of countermeasures to prevent these unwanted adaptations is an important
      requirement. The limited access to microgravity environments for the purpose of
      studying muscle adaptation and evaluating countermeasure programs has
      necessitated the use of ground-based models to conduct both basic and applied
      muscle physiology research. In this review, the published results from ground
      based models of muscle unweighting are presented and compared with the results
      from related spaceflight research. The models of skeletal muscle unweighting with
      a sufficient body of literature included bed rest, cast immobilization, and
      unilateral lower limb suspension. Comparisons of changes in muscle strength and
      size between these models in the context of the limited results available from
      spaceflight suggest that each model may be useful for the investigation of
      certain aspects of the skeletal muscle unweighting that occur in microgravity.

PMID- 14600161
TI  - Heterogeneity of skeletal muscle perfusion and metabolism.

PMID- 14600162
TI  - Stiffness of the pleural surface of the chest wall is similar to that of the
      lung.
AB  - To address the role of the parietal pleura in reduction of mesothelial shear
      stresses during breathing, we measured the stiffness of the parietal pleural
      surface of mammalian chest walls using microindentation. The pleural surface was
      indented over ribs and intercostal spaces with rigid flat punches (tip radii of
      0.01, 0.02, and 0.1 cm) to probe stiffness at length scales comparable with those
      of surface asperities. We found a tissue shear modulus of 6700 dyn/cm2 and
      pleural membrane tension of 4900 dyn/cm, with a geometric standard deviation of
      0.42. These values are similar to those measured for the lung by Hajji et al.,
      using indentation (Hajji MA, Wilson TA, and Lai-Fook SJ. J Appl Physiol Respirat
      Environ Exerc Physiol 47: 175-181, 1979). Surprisingly, the pleural surface over
      ribs and intercostal spaces exhibited similar stiffness. In addition, caudal
      regions exhibited lower stiffness than cranial regions. In the context of
      elastohydrodynamic lubrication, these results suggest that shear-induced
      pressures during breathing deform the chest wall and lung surfaces to a similar
      extent, promoting spatial uniformity of pleural fluid thickness and reducing
      shear stresses.

PMID- 14600164
TI  - Invited review: aging and the cardiovascular system.
AB  - Aging is associated with complex and diversified changes of cardiovascular
      structure and function. The heart becomes slightly hypertrophic and
      hyporesponsive to sympathetic (but not parasympathetic) stimuli, so that the
      exercise-induced increases in heart rate and myocardial contractility are blunted
      in older hearts. The aorta and major elastic arteries become elongated and
      stiffer, with increased pulse wave velocity, evidence of endothelial dysfunction,
      and biochemical patterns resembling early atherosclerosis. The arterial
      baroreflex is sizably altered in aging, but different components are
      differentially affected: there is a definite impairment of arterial baroreceptor
      control of the heart but much better preserved baroreceptor control of peripheral
      vascular resistance. Alterations at the afferent, central neural, efferent, and
      effector organ portions of the reflex arch have been claimed to account for age
      related baroreflex changes, but no conclusive evidence is available on this
      mechanistic aspect. Reflexes arising from cardiopulmonary vagal afferents are
      also blunted in aged individuals. The cardiovascular and reflex changes brought
      about by aging may have significant implications for circulatory homeostasis in
      health and disease.

PMID- 14600163
TI  - No effect of menstrual cycle phase on lactate threshold.
AB  - No previous exercise studies in women have assessed the effects of the normal
      menstrual cycle on the lactate threshold (LT) measured during a graded, maximal
      exercise test. This is relevant to our understanding of exercise training and
      metabolism in eumenorrheic women. The present study, therefore, examined the
      effect of menstrual cycle phase on the LT. Eight moderately active, eumenorrheic
      women performed three maximal exercise tests with simultaneous determination of
      LT. Tests were performed in the early follicular (low estrogen and progesterone),
      midfollicular (elevated estrogen and low progesterone), and midluteal (elevated
      estrogen and progesterone) phases of the menstrual cycle. No significant
      differences were observed in LT measured across phases of the menstrual cycle
      whether data were expressed in absolute terms (1299 +/- 70, 1364 +/- 80, and 1382
      +/- 71 ml O(2)/min, respectively) or relative to maximal oxygen uptake (V(o2
      max); 52.1 +/- 1.7, 54.7 +/- 1.7, and 55.7 +/- 1.6%, respectively). In addition,
      there were no significant cycle phase differences in V(o2 max), maximal heart
      rate, heart rate at LT, or final lactate concentration. With data combined across
      all phases of the menstrual cycle, there was a significant correlation between
      the LT and the epinephrine breakpoint (r = 0.91, P < 0.0002) and norepinephrine
      breakpoint (r = 0.94, P < 0.0001). For epinephrine only, there was close
      correspondence between the epinephrine breakpoint (ml O(2)/min) and the LT. In
      conclusion, LT as well as V(o2 max) and other measures of cardiorespiratory
      fitness are not significantly affected by the changing sex steroid levels
      observed across the normal menstrual cycle. Data suggest that the onset of the
      steep increase in epinephrine determines the LT during graded exercise.

PMID- 14600165
TI  - Invited review: aging and human temperature regulation.
AB  - This mini-review focuses on the effects of aging on human temperature regulation.
      Although comprehensive reviews have been published on this topic (Kenney WL.
      Exercise and Sport Sciences Reviews, Baltimore: Williams & Wilkins, 1997, p. 41
      76; Pandolf KB. Exp Aging Res 17: 189-204, 1991; Van Someren EJ, Raymann RJ,
      Scherder EJ, Daanen HA, and Swaab DF. Ageing Res Rev 1: 721-778, 2002; and Young
      AJ. Exp Aging Res 17: 205-213, 1991), this mini-review concisely summarizes the
      present state of knowledge about human temperature regulation and aging in
      thermoneutral conditions, as well as during hypo- and hyperthermic challenges.
      First, we discuss age-related effects on baseline body core temperature and
      phasing rhythms of the circadian temperature cycle. We then examine the altered
      physiological responses to cold stress that result from aging, including
      attenuated peripheral vasoconstriction and reduced cold-induced metabolic heat
      production. Finally, we present the age-related changes in sweating and
      cardiovascular function associated with heat stress. Although epidemiological
      evidence of increased mortality among older adults from hypo- and hyperthermia
      exists, this outcome does not reflect an inability to thermoregulate with
      advanced age. In fact, studies that have attempted to separate the effects of
      chronological age from concurrent factors, such as fitness level, body
      composition, and the effects of chronic disease, have shown that thermal
      tolerance appears to be minimally compromised by age.

PMID- 14600167
TI  - A piece of my mind. Galileo's grapes: recognizing those who helped make us who we
      are.

PMID- 14600168
TI  - Expanding statin use to help more at-risk patients is causing financial
      heartburn.

PMID- 14600169
TI  - 2003 Nobels awarded for pioneering research in MRI, cellular channels.

PMID- 14600170
TI  - "Best care" would save 57 000 lives.

PMID- 14600175
TI  - Strategies to improve test ordering in primary care.

PMID- 14600176
TI  - Definitions of terrorism.

PMID- 14600177
TI  - Use of the Internet for health information and communication.

PMID- 14600178
TI  - Use of the Internet for health information and communication.

PMID- 14600179
TI  - Use of the Internet for health information and communication.

PMID- 14600180
TI  - Use of the Internet for health information and communication.

PMID- 14600181
TI  - Use of the Internet for health information and communication.

PMID- 14600182
TI  - Use of the Internet for health information and communication.

PMID- 14600183
TI  - Frequency of health-related search terms on the Internet.

PMID- 14600184
TI  - Association between estrogen receptor alpha gene variation and cardiovascular
      disease.
AB  - CONTEXT: Estrogen and related hormone therapies activate estrogen receptors,
      which in turn regulate genes for several cardiovascular disease (CVD) risk
      factors. Relatively little is known, however, about the impact of genetic
      variation in estrogen receptor alpha (ESR1) on CVD risk. OBJECTIVE: To
      investigate whether the ESR1 c.454-397T>C polymorphism is associated with CVD
      risk. DESIGN, SETTING, AND PARTICIPANTS: Prospective study of 1739 unrelated men
      and women from the population-based offspring cohort of the Framingham Heart
      Study, who were followed up from 1971 to 1998. MAIN OUTCOME MEASURES: Total
      atherosclerotic CVD events, defined as recognized or unrecognized myocardial
      infarction (MI), angina pectoris, coronary insufficiency, intermittent
      claudication, coronary heart disease death, or atherothrombotic stroke (n = 178);
      major atherosclerotic CVD, defined as recognized acute MI, coronary
      insufficiency, coronary heart disease death, or atherothrombotic stroke (n = 83);
      and recognized acute MI (n = 59). RESULTS: Twenty percent of participants (n =
      352) were homozygous for the ESR1 c.454-397C allele. After adjustment for
      covariates (age, sex, body mass index, hypertension, diabetes mellitus, total
      cholesterol, high-density lipoprotein cholesterol, and cigarette smoking), the CC
      genotype was significantly associated with major atherosclerotic CVD, with an
      odds ratio of 2.0 (95% confidence interval [CI], 1.3-3.2; P =.004) compared with
      individuals with the CT or TT genotypes. Participants with the CC genotype had
      3.0-fold greater odds of MI (95% CI, 1.7-5.2; P<.001) compared with those with
      the CT or TT genotype. The results remained significant when analyses were
      restricted to men; too few women had events to study them separately.
      CONCLUSIONS: Individuals with the common ESR1 c.454-397CC genotype have a
      substantial increase in risk of MI. Whether ESR1 c.454-397T>C is causally related
      to MI risk or in linkage disequilibrium with 1 or more causal variants remains to
      be determined. These findings support the importance of estrogen receptors in CVD
      susceptibility, especially in men. Estrogen receptor variation also has potential
      to explain recent conflicting data regarding the effects of hormone therapy on
      CVD susceptibility in women.

PMID- 14600185
TI  - Childhood cardiovascular risk factors and carotid vascular changes in adulthood:
      the Bogalusa Heart Study.
AB  - CONTEXT: Carotid artery intima-media thickness (IMT) is associated with
      cardiovascular risk factors and is recognized as an important predictive measure
      of clinical coronary atherosclerosis events in middle-aged and elderly
      populations. However, information on the association of carotid IMT in young
      adults with different risk factors measured in childhood, adulthood, or as a
      cumulative burden of each of the risk factors measured serially from childhood to
      adulthood is limited. OBJECTIVE: To examine the association between carotid IMT
      in young adults and traditional cardiovascular risk factors measured since
      childhood. DESIGN, SETTING, AND PARTICIPANTS: A cohort study of 486 adults aged
      25 to 37 years from a semirural black and white community in Bogalusa, La (71%
      white, 39% men), who had at least 3 measurements of traditional risk factors
      since childhood, conducted between September 1973 and December 1996. MAIN OUTCOME
      MEASURE: Association of carotid IMT with risk factors, including systolic blood
      pressure, lipoprotein levels, and body mass index. RESULTS: Male vs female (0.757
      mm vs 0.719 mm) and black vs white (0.760 mm vs 0.723 mm) participants had
      increased carotid IMT (P<.001 for both). In multivariable analyses, significant
      predictors for being in top vs lower 3 quartiles of carotid IMT in young adults
      were childhood measures of low-density lipoprotein cholesterol (LDL-C) level
      (odds ratio [OR], 1.42, corresponding to 1-SD change specific for age, race, and
      sex; 95% confidence interval [CI], 1.14-1.78) and body mass index (BMI; OR, 1.25;
      95% CI, 1.01-1.54); adulthood measures of LDL-C level (OR, 1.46; 95% CI, 1.16
      1.82), high-density lipoprotein cholesterol (HDL-C) level (OR, 0.67; 95% CI, 0.51
      0.88), and systolic blood pressure (OR, 1.36; 95% CI, 1.08-1.72); and long-term
      cumulative burden of LDL-C (OR, 1.58; 95% CI, 1.24-2.01) and HDL-C (OR, 0.75; 95%
      CI, 0.58-0.97) levels measured serially from childhood to adulthood. An
      increasing trend in carotid IMT across quartiles of LDL-C level measured in
      childhood was observed, with a mean value of 0.761 mm (95% CI, 0.743-0.780 mm)
      for those at the top quartile vs 0.724 mm (95% CI, 0.715-0.734 mm) for those in
      the lower 3 quartiles (P<.001). CONCLUSIONS: Childhood measures of LDL-C level
      and BMI predict carotid IMT in young adults. The prevention implications of these
      findings remains to be explored.

PMID- 14600186
TI  - Cardiovascular risk factors in childhood and carotid artery intima-media
      thickness in adulthood: the Cardiovascular Risk in Young Finns Study.
AB  - CONTEXT: Exposure to cardiovascular risk factors during childhood and adolescence
      may be associated with the development of atherosclerosis later in life.
      OBJECTIVE: To study the relationship between cardiovascular risk factors measured
      in childhood and adolescence and common carotid artery intima-media thickness
      (IMT), a marker of preclinical atherosclerosis, measured in adulthood. DESIGN,
      SETTING, AND PARTICIPANTS: Population-based, prospective cohort study conducted
      at 5 centers in Finland among 2229 white adults aged 24 to 39 years who were
      examined in childhood and adolescence at ages 3 to 18 years in 1980 and
      reexamined 21 years later, between September 2001 and January 2002. MAIN OUTCOME
      MEASURES: Association between cardiovascular risk variables (levels of low
      density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol
      [HDL-C], and triglycerides; LDL-C/HDL-C ratio; systolic and diastolic blood
      pressure; body mass index; smoking) measured in childhood and adulthood and
      common carotid artery IMT measured in adulthood. RESULTS: In multivariable models
      adjusted for age and sex, IMT in adulthood was significantly associated with
      childhood LDL-C levels (P =.001), systolic blood pressure (P<.001), body mass
      index (P =.007), and smoking (P =.02), and with adult systolic blood pressure
      (P<.001), body mass index (P<.001), and smoking (P =.004). The number of risk
      factors measured in 12- to 18-year-old adolescents, including high levels (ie,
      extreme age- and sex-specific 80th percentile) of LDL-C, systolic blood pressure,
      body mass index, and cigarette smoking, were directly related to carotid IMT
      measured in young adults at ages 33 through 39 years (P<.001 for both men and
      women), and remained significant after adjustment for contemporaneous risk
      variables. The number of risk factors measured at ages 3 to 9 years demonstrated
      a weak direct relationship with carotid IMT at ages 24 to 30 years in men (P
      =.02) but not in women (P =.63). CONCLUSIONS: Risk factor profile assessed in 12-
      to 18-year-old adolescents predicts adult common carotid artery IMT independently
      of contemporaneous risk factors. These findings suggest that exposure to
      cardiovascular risk factors early in life may induce changes in arteries that
      contribute to the development of atherosclerosis.

PMID- 14600187
TI  - Fenoldopam mesylate for the prevention of contrast-induced nephropathy: a
      randomized controlled trial.
AB  - CONTEXT: The development of contrast-induced nephropathy in patients undergoing
      invasive cardiac procedures is associated with a marked increase in
      cardiovascular morbidity and mortality. Fenoldopam mesylate, a specific agonist
      of the dopamine-1 receptor, preserves renal blood flow after iodinated contrast
      administration and has shown promise in ameliorating contrast nephropathy in
      previous observational and small randomized trials. OBJECTIVE: To examine the
      efficacy of fenoldopam mesylate in preventing contrast nephropathy after invasive
      cardiovascular procedures. DESIGN: Prospective, placebo-controlled, double-blind,
      multicenter randomized trial with serial serum creatinine levels measured at a
      central biochemistry laboratory (at baseline and 1, 24, 48, and 72 to 96 hours
      after study drug administration) and 30-day clinical follow-up. PATIENTS AND
      SETTING: Between March 2001 and July 2002, 315 patients with creatinine clearance
      less than 60 mL/min (1.00 mL/s) at 28 centers in the United States were
      randomized to receive fenoldopam mesylate (n = 157) or placebo (n = 158).
      INTERVENTIONS: Patients were hydrated and randomized to receive intravenous
      fenoldopam (0.05 microg/kg/min titrated to 0.10 microg/kg/min) vs matching
      placebo, starting 1 hour prior to angiography and continuing for 12 hours. MAIN
      OUTCOME MEASURE: Contrast-induced nephropathy, defined as an increase of 25% or
      more in serum creatinine level within 96 hours postprocedure. RESULTS: Mean (SD)
      patient age was 70 (11) years, and 49% had diabetes mellitus. Mean (SD) baseline
      creatinine clearance was 29.0 (10.0) mL/min (0.48 [0.16] mL/s) (range, 7.5-56.8
      mL/min [0.12-0.94 mL/s]), and 157 (108) mL of contrast was administered during
      the procedures. The primary end point of contrast-induced nephropathy occurred in
      33.6% of patients assigned to receive fenoldopam vs 30.1% assigned to receive
      placebo (relative risk, 1.11; 95% confidence interval, 0.79-1.57; P =.61). There
      were no significant differences in the 30-day rates of death (2.0% vs 3.8%, P
      =.50), dialysis (2.6% vs 1.9%, P =.72), or rehospitalization (17.6% vs 19.9%, P
      =.66) in fenoldopam vs placebo randomized patients, respectively. CONCLUSION: The
      selective dopamine-1 agonist fenoldopam mesylate does not prevent further renal
      function deterioration after contrast administration in patients with chronic
      renal insufficiency.

PMID- 14600188
TI  - Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with
      acute coronary syndromes: a randomized controlled trial.
AB  - CONTEXT: Although low levels of high-density lipoprotein cholesterol (HDL-C)
      increase risk for coronary disease, no data exist regarding potential benefits of
      administration of HDL-C or an HDL mimetic. ApoA-I Milano is a variant of
      apolipoprotein A-I identified in individuals in rural Italy who exhibit very low
      levels of HDL. Infusion of recombinant ApoA-I Milano-phospholipid complexes
      produces rapid regression of atherosclerosis in animal models. OBJECTIVE: We
      assessed the effect of intravenous recombinant ApoA-I Milano/phospholipid
      complexes (ETC-216) on atheroma burden in patients with acute coronary syndromes
      (ACS). DESIGN: The study was a double-blind, randomized, placebo-controlled
      multicenter pilot trial comparing the effect of ETC-216 or placebo on coronary
      atheroma burden measured by intravascular ultrasound (IVUS). SETTING: Ten
      community and tertiary care hospitals in the United States. PATIENTS: Between
      November 2001 and March 2003, 123 patients aged 38 to 82 years consented, 57 were
      randomly assigned, and 47 completed the protocol. INTERVENTIONS: In a ratio of
      1:2:2, patients received 5 weekly infusions of placebo or ETC-216 at 15 mg/kg or
      45 mg/kg. Intravascular ultrasound was performed within 2 weeks following ACS and
      repeated after 5 weekly treatments. MAIN OUTCOME MEASURES: The primary efficacy
      parameter was the change in percent atheroma volume (follow-up minus baseline) in
      the combined ETC-216 cohort. Prespecified secondary efficacy measures included
      the change in total atheroma volume and average maximal atheroma thickness.
      RESULTS: The mean (SD) percent atheroma volume decreased by -1.06% (3.17%) in the
      combined ETC-216 group (median, -0.81%; 95% confidence interval [CI], -1.53% to 
      0.34%; P =.02 compared with baseline). In the placebo group, mean (SD) percent
      atheroma volume increased by 0.14% (3.09%; median, 0.03%; 95% CI, -1.11% to
      1.43%; P =.97 compared with baseline). The absolute reduction in atheroma volume
      in the combined treatment groups was -14.1 mm3 or a 4.2% decrease from baseline
      (P<.001). CONCLUSIONS: A recombinant ApoA-I Milano/phospholipid complex (ETC-216)
      administered intravenously for 5 doses at weekly intervals produced significant
      regression of coronary atherosclerosis as measured by IVUS. Although promising,
      these results require confirmation in larger clinical trials with morbidity and
      mortality end points.

PMID- 14600189
TI  - Contemporary management of chronic obstructive pulmonary disease: scientific
      review.
AB  - CONTEXT: The care of patients with chronic obstructive pulmonary disease (COPD)
      has changed radically over the past 2 decades, and novel therapies can not only
      improve the health status of patients with COPD but also modify its natural
      course. OBJECTIVE: To systematically review the impact of long-acting
      bronchodilators, inhaled corticosteroids, nocturnal noninvasive mechanical
      ventilation, pulmonary rehabilitation, domiciliary oxygen therapy, and disease
      management programs on clinical outcomes in patients with COPD. DATA SOURCES:
      MEDLINE and Cochrane databases were searched to identify all randomized
      controlled trials and systematic reviews from 1980 to May 2002 evaluating
      interventions in patients with COPD. We also hand searched bibliographies of
      relevant articles and contacted experts in the field. STUDY SELECTION AND DATA
      EXTRACTION: We included randomized controlled trials that had follow-up of at
      least 3 months and contained data on at least 1 of these clinical outcomes:
      health-related quality of life, exacerbations associated with COPD, or death. For
      pulmonary rehabilitation, we included studies that had a follow-up of at least 6
      weeks. Using standard meta-analytic techniques, the effects of interventions were
      compared with placebo or with usual care. In secondary analyses, the effects of
      interventions were compared against each other, where possible. DATA SYNTHESIS:
      Long-acting beta2-agonists and anticholinergics (tiotropium) reduced exacerbation
      rates by approximately 20% to 25% (relative risk [RR] for long-acting beta2
      agonists, 0.79; 95% CI, 0.69-0.90; RR for tiotropium, 0.74; 95% CI, 0.62-0.89) in
      patients with moderate to severe COPD. Inhaled corticosteroids also reduced
      exacerbation rates by a similar amount (RR, 0.76; 95% CI, 0.72-0.80). The
      beneficial effects were most pronounced in trials enrolling patients with FEV1
      between 1 L and 2 L. Combining a long-acting beta2-agonist with an inhaled
      corticosteroid resulted in an approximate 30% (RR, 0.70; 95% CI, 0.62-0.78)
      reduction in exacerbations. Pulmonary rehabilitation improved the health status
      of patients with moderate to severe disease, but no material effect was observed
      on long-term survival or hospitalization rates. Domiciliary oxygen therapy
      improved survival by approximately 40% in patients with PaO2 lower than 60 mm Hg,
      but not in those without hypoxia at rest. The data on disease management programs
      were heterogeneous, but overall no effect was observed on survival or risk of
      hospitalization. Noninvasive mechanical ventilation was not associated with
      improved outcomes. CONCLUSIONS: A significant body of evidence supports the use
      of long-acting bronchodilators and inhaled corticosteroids in reducing
      exacerbations in patients with moderate to severe COPD. Domiciliary oxygen
      therapy is the only intervention that has been demonstrated to prolong survival,
      but only in patients with resting hypoxia.

PMID- 14600190
TI  - Contemporary management of chronic obstructive pulmonary disease: clinical
      applications.
AB  - The presentation of chronic obstructive pulmonary disease (COPD) usually is
      insidious, and many patients are undiagnosed until the disease is far advanced.
      Therefore, the early use of spirometry is recommended for anyone who is suspected
      to have COPD. In the early stages of the disease, the patient is only mildly
      symptomatic (cough and sputum production). As COPD becomes more advanced,
      functional impairment in the form of chronic dyspnea occurs and acute
      exacerbations of symptoms become more frequent, contributing to overall morbidity
      and mortality. The single most important known causative factor of COPD is
      cigarette smoking. Smoking cessation remains, therefore, the mainstay of COPD
      therapy. In patients with advanced disease, symptomatic treatment with the
      regular use of either short- or long-acting sympathomimetic and/or
      anticholinergic bronchodilators, singly or in combination, should be added to
      smoking cessation and influenza and pneumococcal vaccination therapies. An
      inhaled corticosteroid, either alone or more commonly in combination with a long
      acting bronchodilator, can further reduce exacerbations and improve the health
      status of these patients. Furthermore, patients with severe COPD, particularly
      those who are debilitated, should be considered for pulmonary rehabilitation
      because these programs have been proven useful in maintaining, or in some cases
      improving, health status for these patients. Finally, correction of resting
      arterial hypoxemia with oxygen therapy for more than 15 h/d prolongs survival of
      COPD patients for those with a resting PaO2 lower than 55 to 60 mm Hg.

PMID- 14600191
TI  - Estrogen receptor 1 variants and coronary artery disease: shedding light into a
      murky pool.

PMID- 14600192
TI  - Starting earlier to prevent heart disease.

PMID- 14600194
TI  - MSJAMA. History of medicine.

PMID- 14600193
TI  - High-density lipoproteins as an emerging therapeutic target for atherosclerosis.

PMID- 14600195
TI  - MSJAMA. Neurasthenia and a modernizing America.

PMID- 14600196
TI  - MSJAMA. The physicians' dilemma in the 18th-century French smallpox debate.

PMID- 14600197
TI  - MSJAMA. Uses of Jacobson v Massachusetts in the age of bioterror.

PMID- 14600198
TI  - JAMA patient page. Chronic obstructive pulmonary disease.

PMID- 14600199
TI  - A novel fingerprint for the characterization of protein folds.
AB  - A novel fingerprint, defined without the use of distances, is introduced to
      characterize protein folds. It is of the form of binary matrices whose elements
      are defined by angles between the C=O direction, the backbone axis and the line
      connecting the alpha-carbons of the various residues. It is shown that matches in
      the fingerprint matrices correspond to low r.m.s.d.

PMID- 14600200
TI  - On the rotational operators in protein structure simulations.
AB  - The reduction of the computational complexity of the algorithms dealing with
      protein structure analysis and conformation predictions is of prime importance.
      One common element in most of these algorithms is the process of transforming
      geometrical information between dihedral angles and Cartesian coordinates of the
      atoms in the protein using rotational operators. In the literature, the operators
      used in protein structures are rotation matrices, quaternions in vector and
      matrix forms and the Rodrigues-Gibbs formula. In the protein structure-related
      literature, the most widely promoted rotational operator is the quaternions
      operator. In this work, we studied the computational efficiency of the
      mathematical operations of the above rotational operators applied to protein
      structures. A similar study applied to protein structures has not been reported
      previously. We concluded that the computational efficiency of these rotational
      operators applied to protein chains is different from those reported for other
      applications (such as mechanical machinery) and the conclusions are not
      analogous. Rotation matrices are the most efficient mathematical operators in the
      protein chains. We examined our findings in two protein molecules: Ab1 tyrosine
      kinase and heparin-binding growth factor 2. We found that the rotation matrix
      operator has between 2 and 187% fewer mathematical operations than the other
      rotational operators.

PMID- 14600201
TI  - Common active site architecture and binding strategy of four phenylpropanoid
      P450s from Arabidopsis thaliana as revealed by molecular modeling.
AB  - Despite extensive primary sequence diversity, crystal structures of several
      bacterial cytochrome P450 monooxygenases (P450s) and a single eukaryotic P450
      indicate that these enzymes share a structural core of alpha-helices and beta
      sheets and vary in the loop regions contacting individual substrates. To
      determine the extent to which individual structural features are conserved among
      divergent P450s existing in a single biosynthetic pathway, we have modeled the
      structures of four highly divergent P450s (CYP73A5, CYP84A1, CYP75B1, CYP98A3) in
      the Arabidopsis phenylpropanoid pathway synthesizing lignins, flavonoids and
      anthocyanins. Analysis of these models has indicated that, despite primary
      sequence identities as low as 13%, the structural cores and several loop regions
      of these P450s are highly conserved. Substrate docking indicated that all four
      enzymes employ a common strategy to identify their substrates in that their
      cinnamate-derived substrates align along helix I with their aromatic ring
      positioned towards the C-terminus of this helix and their aliphatic tails
      positioned towards the N-terminus. Further similarity was observed in the way the
      substrates contact the consensus P450 substrate recognition sites (SRS). Residues
      predicted to contact the aromatic ring region exist in SRS5, SRS6 and the C
      terminal portion of SRS4 and residues contacting the distal end of each substrate
      exist in SRS1, SRS2 and the N-terminal portion of SRS4. Alignments of the regions
      contacting the aromatic ring region indicate that SRS4, SRS5 and SRS6 share
      higher degrees of sequence conservation than found in SRS1, SRS2 or the full
      length protein.

PMID- 14600202
TI  - Role of the tyrosine corner motif in the stability of neocarzinostatin.
AB  - Although the immunoglobulin-like beta-sandwich fold has no specifically conserved
      function, some common structural features have been observed, in particular a
      structural motif, the tyrosine corner. Such a motif was described in
      neocarzinostatin (NCS), a bacterial protein the structure of which is very
      similar to that of the immunoglobulin domain. Compared with the other beta-sheet
      proteins, the NCS 'tyrosine corner' presents non-standard structural features. To
      investigate the role of this motif in the NCS structure and stability, we studied
      the properties of a mutant where the H bond interaction had been eliminated by
      replacing the tyrosine with a phenylalanine. This mutation costs 4.0 kcal/mol
      showing that the NCS 'tyrosine corner' is involved in protein stability as in the
      other Greek key proteins. This destabilization is accompanied by remote
      structural effects, including modification of the binding properties, suggesting
      an increase in the internal flexibility of the protein. With a view to using this
      protein for drug targeting, these results along with those obtained previously
      allow us to define clearly the limitations of the modifications that can be
      performed on this scaffold.

PMID- 14600203
TI  - Structure-based substitutions for increased solubility of a designed protein.
AB  - Manipulation of protein solubility is important for many aspects of protein
      design and engineering. Previously, we designed a series of consensus ankyrin
      repeat proteins containing one, two, three and four identical repeats (1ANK,
      2ANK, 3ANK and 4ANK). These proteins, particularly 4ANK, are intended for use as
      a universal scaffold on which specific binding sites can be constructed. Despite
      being well folded and extremely stable, 4ANK is soluble only under acidic
      conditions. Designing interactions with naturally occurring proteins requires the
      designed protein to be soluble at physiological pH. Substitution of six leucines
      with arginine on exposed hydrophobic patches on the surface of 4ANK resulted in
      increased solubility over a large pH range. Study of the pH dependence of
      stability demonstrated that 4ANK is one of the most stable ankyrin repeat
      proteins known. In addition, analogous leucine to arginine substitutions on the
      surface of 2ANK allowed the partially folded protein to assume a fully folded
      conformation. Our studies indicate that replacement of surface-exposed
      hydrophobic residues with positively charged residues can significantly improve
      protein solubility at physiological pH.

PMID- 14600204
TI  - Fine mapping and structural analysis of immunodominant IgE allergenic epitopes in
      chicken egg ovalbumin.
AB  - Ovalbumin is a major allergen in hen egg white that causes IgE-mediated food
      allergic reactions in children. In this study, the immunodominant IgE-binding
      epitopes of ovalbumin were mapped using arrays of overlapping peptides
      synthesized on activated cellulose membranes. Pooled human sera from 18 patients
      with egg allergy were used to probe the membrane. Five distinct regions were
      found to contain dominant allergic IgE epitopes, these being L38T49, D95A102,
      E191V200, V243E248 and G251N260. The critical amino acids involved in IgE
      antibody binding were also determined. These epitopes were composed primarily of
      hydrophobic amino acids, followed by polar and charged residues and being
      comprised of beta-sheet and beta-turn structures. One epitope, D95A102, consisted
      of a single alpha-helix. These results provide useful information on the
      functional role of amino acid residues to evaluate the structure-function
      relationships and structural properties of allergic epitopes in ovalbumin. They
      also provide a strategic approach for engineering ovalbumin to reduce its
      allergenicity.

PMID- 14600205
TI  - Specificity grafting of human antibody frameworks selected from a phage display
      library: generation of a highly stable humanized anti-CD22 single-chain Fv
      fragment.
AB  - A prerequisite for the enrichment of antibodies screened from phage display
      libraries is their stable expression on a phage during multiple selection rounds.
      Thus, if stringent panning procedures are employed, selection is simultaneously
      driven by antigen affinity, stability and solubility. To take advantage of robust
      pre-selected scaffolds of such molecules, we grafted single-chain Fv (scFv)
      antibodies, previously isolated from a human phage display library after multiple
      rounds of in vitro panning on tumor cells, with the specificity of the clinically
      established murine monoclonal anti-CD22 antibody RFB4. We show that a panel of
      grafted scFvs retained the specificity of the murine monoclonal antibody, bound
      to the target antigen with high affinity (6.4-9.6 nM), and exhibited exceptional
      biophysical stability with retention of 89-93% of the initial binding activity
      after 6 days of incubation in human serum at 37 degrees C. Selection of stable
      human scaffolds with high sequence identity to both the human germline and the
      rodent frameworks required only a small number of murine residues to be retained
      within the human frameworks in order to maintain the structural integrity of the
      antigen binding site. We expect this approach may be applicable for the rapid
      generation of highly stable humanized antibodies with low immunogenic potential.

PMID- 14600206
TI  - Tailoring structure-function and pharmacokinetic properties of single-chain Fv
      proteins by site-specific PEGylation.
AB  - The utility of single-chain Fv proteins as therapeutic agents would be realized
      if the circulating lives of these minimal antigen-binding polypeptides could be
      both prolonged and adjustable. We have developed a general strategy for creating
      tailored monoPEGylated single-chain antibodies. Free cysteine residues were
      engineered in an anti-TNF-alpha scFv at the C-terminus or within the linker
      segments of both scFv orientations, V(L)-linker-V(H) and V(H)-linker-V(L). High
      level expression of 10 designed variant scFv proteins in Pichia pastoris allowed
      rapid purification. Optimization of site-specific conjugate preparation with 5,
      20 and 40 kDa maleimide-PEG polymers was achieved and a comparison of the
      structural and functional properties of the scFv proteins and their PEGylated
      counterparts was performed. Peptide mapping and MALDI-TOF mass spectrometric
      analysis confirmed the unique attachment site for each PEG polymer. Independent
      biochemical and bioactivity analyses, including binding affinities and kinetics,
      antigenicity, flow cytometric profiling and cell cytotoxicity rescue,
      demonstrated that the functional activities of the 10 designed scFv conjugates
      are maintained, while scFv activity variations between these alternative assays
      can be correlated with conjugate and analytical designs. Pharmacokinetic studies
      of the PEGylated scFv in mice demonstrated up to 100-fold prolongation of
      circulating lives, in a range comparable to clinical antibodies.

PMID- 14600207
TI  - Chimeric ribonuclease as a source of human adapter protein for targeted drug
      delivery.
AB  - Assembled modular complexes for targeted drug delivery can be based on strong non
      covalent interactions between a cargo module containing an adapter protein and a
      docking tag fused to a targeting protein. We have recently constructed a
      completely humanized adapter/docking tag system based on interactions between 15
      amino acid (Hu-tag) and 110 amino acid (HuS) fragments of human ribonuclease I
      (RNase I). Although recombinant HuS can be expressed and refolded into a
      functionally active form, the purification procedure is cumbersome and expensive,
      and more importantly, it yields a significant proportion of improperly folded
      proteins. Here we describe engineering, high-yield expression, and purification
      of a chimeric bovine/human RNase (BH-RNase) comprising 1-29 N-terminal amino
      acids of bovine ribonuclease A and 30-127 amino acids of human RNase I. Unlike
      RNase I, the chimeric BH-RNase can be cleaved by either subtilisin or proteinase
      K between A20 and S21, providing a functionally active HuS. The HuS obtained from
      chimeric BH-RNase differs from wild-type HuS by an N24T substitution; therefore,
      we have reverted this substitution by mutating N24 to T24 in BH-RNase. This BH
      RNase mutant can also be cleaved by subtilisin or proteinase K yielding wild-type
      HuS. The affinity of HuS obtained from BH-RNase to Hu-tag is approximately five
      times higher than that for recombinant HuS, reflecting a higher percentage of
      properly folded proteins.

PMID- 14600208
TI  - Precise and efficient cleavage of recombinant fusion proteins using mammalian
      aspartic proteases.
AB  - Expression of recombinant proteins as translational fusions is commonly employed
      to enhance stability, increase solubility and facilitate purification of the
      desired protein. In general, such fusion proteins must be cleaved to release the
      mature protein in its native form. The usefulness of the procedure depends on the
      efficiency and precision of cleavage and its cost per unit activity. We report
      here the development of a general procedure for precise and highly efficient
      cleavage of recombinant fusion proteins using the protease chymosin. DNA encoding
      a modified pro-peptide from bovine chymosin was fused upstream of hirudin, carp
      growth hormone, thioredoxin and cystatin coding sequences and expressed in a
      bacterial Escherichia coli host. Each of the resulting fusion proteins was
      efficiently cleaved at the junction between the pro-peptide and the desired
      protein by the addition of chymosin, as determined by activity, N-terminal
      sequencing and mass spectrometry of the recovered protein. The system was tested
      further by cleavage of two fusion proteins, cystatin and thioredoxin, sequestered
      on oilbody particles obtained from transgenic Arabidopsis seeds. Even when the
      fusion protein was sequestered and immobilized on oilbodies, precise and
      efficient cleavage was obtained. The precision, efficiency and low cost of this
      procedure suggest that it could be used in larger scale manufacturing of
      recombinant proteins which benefit from expression as fusions in their host
      organism.

PMID- 14600209
TI  - Similar neural mechanisms for emotion-induced memory impairment and enhancement.

PMID- 14600210
TI  - The bifunctional role of hexokinase in metabolism and glucose signaling.

PMID- 14600211
TI  - Update on the basic helix-loop-helix transcription factor gene family in
      Arabidopsis thaliana.

PMID- 14600212
TI  - Disruption of the two digalactosyldiacylglycerol synthase genes DGD1 and DGD2 in
      Arabidopsis reveals the existence of an additional enzyme of galactolipid
      synthesis.
AB  - Two genes (DGD1 and DGD2) are involved in the synthesis of the chloroplast lipid
      digalactosyldiacylglycerol (DGDG). The role of DGD2 for galactolipid synthesis
      was studied by isolating Arabidopsis T-DNA insertional mutant alleles (dgd2-1 and
      dgd2-2) and generating the double mutant line dgd1 dgd2. Whereas the growth and
      lipid composition of dgd2 were not affected, only trace amounts of DGDG were
      found in dgd1 dgd2. The growth and photosynthesis of dgd1 dgd2 were affected more
      severely compared with those of dgd1, indicating that the residual amount of DGDG
      in dgd1 is crucial for normal plant development. DGDG synthesis was increased
      after phosphate deprivation in the wild type, dgd1, and dgd2 but not in dgd1
      dgd2. Therefore, DGD1 and DGD2 are involved in DGDG synthesis during phosphate
      deprivation. DGD2 was localized to the outer side of chloroplast envelope
      membranes. Like DGD2, heterologously expressed DGD1 uses UDP-galactose for
      galactosylation. Galactolipid synthesis activity for monogalactosyldiacylglycerol
      (MGDG), DGDG, and the unusual oligogalactolipids tri- and
      tetragalactosyldiacylglycerol was detected in isolated chloroplasts of all mutant
      lines, including dgd1 dgd2. Because dgd1 and dgd2 carry null mutations, an
      additional, processive galactolipid synthesis activity independent from DGD1 and
      DGD2 exists in Arabidopsis. This third activity, which is related to the
      Arabidopsis galactolipid:galactolipid galactosyltransferase, is localized to
      chloroplast envelope membranes and is capable of synthesizing DGDG from MGDG in
      the absence of UDP-galactose in vitro, but it does not contribute to net
      galactolipid synthesis in planta.

PMID- 14600213
TI  - Influence of diet and genetics on hypertension and renal disease in Dahl salt
      sensitive rats.
AB  - Experiments examined the influence of diet and genetics on hypertension and renal
      disease in inbred Dahl salt-sensitive (SS/Mcw) rats and consomic rats in which
      chromosomes 16 (SS.BN16) or 18 (SS.BN18) of the normotensive Brown Norway rat
      were inserted into the genetic background of the SS/Mcw. Dahl SS/Mcw breeders and
      offspring were randomly placed on a purified AIN-76A diet or a grain-based diet,
      and male offspring were screened for cardiovascular and renal phenotypes
      following 3 wk on a 4.0% NaCl diet. High-salt arterial blood pressure (162 +/- 5
      mmHg, n = 10), urinary protein excretion (147 +/- 16 mg/day, n = 14), and albumin
      excretion (72 +/- 9 mg/day, n = 14) were significantly elevated in the Dahl
      SS/Mcw maintained on the purified diet compared with rats fed the grain-based
      diet. Rats fed the purified diet also exhibited significantly more renal
      glomerular and tubular damage than rats fed the grain diet. Moreover, feeding the
      purified diet to the parents led to a significant increase in blood pressure in
      the offspring, regardless of offspring diet. Similar dietary effects were
      observed in SS.BN16 and SS.BN18 rats. In rats fed the purified diet, substitution
      of chromosomes 16 or 18 led to a significant decrease in arterial blood pressure,
      albumin excretion, and protein excretion compared with the SS/Mcw. Chromosomal
      substitution did not, however, affect albumin or protein excretion in the
      consomic rats compared with the SS/Mcw when the rats were maintained on the grain
      diet. These data demonstrate a significant influence of diet composition on salt
      induced hypertension and renal disease in the Dahl SS/Mcw rat.

PMID- 14600214
TI  - Identification of genomic islands in the genome of Bacillus cereus by comparative
      analysis with Bacillus anthracis.
AB  - Horizontal gene transfer has been recognized as a universal event throughout
      bacterial evolution. The availability of both complete genome sequences of
      Bacillus cereus and B. anthracis provides the possibility to perform comparative
      analysis based on their genomes. By using a windowless method to display the
      distribution of the genomic GC content of B. cereus and B. anthracis, we have
      found three genomic islands in the genome of B. cereus, i.e., BCGI-1, BCGI-2, and
      BCGI-3, respectively, which are absent in the genome of B. anthracis. All the
      genomic islands have abrupt changes in GC content compared with that of
      surrounding regions. BCGI-1 has many conserved features of genomic islands, e.g.,
      a Val-tRNA gene is utilized as the integration site, and a site-specific
      recombinase gene is located at the 3' end. BCGI-2 has a large percentage of phage
      protein, suggesting a phage-related recombination is involved. BCGI-3 contains a
      ferric anguibactin transport system, which is likely to be involved in the iron
      transport that enables the bacterium to overcome the iron limitation in the host.
      In addition, BCGI-3 also contains a cluster of genes related to lantibiotics,
      which may play a role during the evolution of the genome. Furthermore, the
      integrations of the genomic islands, BCGI-1 and BCGI-3, result in deletions of
      DNA sequence fragments; therefore, such integrations lead to both gene gain and
      gene loss simultaneously.

PMID- 14600215
TI  - The plasmid genome database.

PMID- 14600216
TI  - JWS online cellular systems modelling and microbiology.

PMID- 14600217
TI  - MvaT proteins in Pseudomonas spp.: a novel class of H-NS-like proteins.

PMID- 14600218
TI  - Type II protein secretion and its relationship to bacterial type IV pili and
      archaeal flagella.
AB  - Homologues of the protein constituents of the Klebsiella pneumoniae (Klebsiella
      oxytoca) type II secreton (T2S), the Pseudomonas aeruginosa type IV
      pilus/fimbrium biogenesis machinery (T4P) and the Methanococcus voltae flagellum
      biogenesis machinery (Fla) have been identified. Known constituents of these
      systems include (1). a major prepilin (preflagellin), (2). several minor
      prepilins (preflagellins), (3). a prepilin (preflagellin) peptidase/methylase,
      (4). an ATPase, (5). a multispanning transmembrane (TM) protein, (6). an outer
      membrane secretin (lacking in Fla) and (7). several functionally uncharacterized
      envelope proteins. Sequence and phylogenetic analyses led to the conclusion that,
      although many of the protein constituents are probably homologous, extensive
      sequence divergence during evolution clouds this homology so that a common
      ancestry can be established for all three types of systems for only two
      constituents, the ATPase and the TM protein. Sequence divergence of the
      individual T2S constituents has occurred at characteristic rates, apparently
      without shuffling of constituents between systems. The same is probably also true
      for the T4P and Fla systems. The family of ATPases is much larger than the family
      of TM proteins, and many ATPase homologues function in capacities unrelated to
      those considered here. Many phylogenetic clusters of the ATPases probably exhibit
      uniform function. Some of these have a corresponding TM protein homologue
      although others probably function without one. It is further shown that proteins
      that compose the different phylogenetic clusters in both the ATPase and the TM
      protein families exhibit unique structural characteristics that are of probable
      functional significance. The TM proteins are shown to have arisen by at least two
      dissimilar intragenic duplication events, one in the bacterial kingdom and one in
      the archaeal kingdom. The archaeal TM proteins are twice as large as the
      bacterial TM proteins, suggesting an oligomeric structure for the latter.

PMID- 14600219
TI  - Transcriptional regulation of Pseudomonas aeruginosa rhlR, encoding a quorum
      sensing regulatory protein.
AB  - The Pseudomonas aeruginosa rhlR gene encodes the transcriptional regulator RhlR
      which has a central role in the quorum-sensing response. Different gene products
      involved in bacterial pathogenesis are regulated at the transcriptional level by
      two quorum-sensing response systems, Las and Rhl. The expression of rhlR has been
      reported to be under the control of the Las system, but its transcriptional
      regulation has not been studied in detail. Here, the rhlR promoter region has
      been characterized and shown to present four different transcription start sites,
      two of which are included in the upstream gene (rhlB) coding region. It was found
      that rhlR expression is not only dependent on LasR but also on different
      regulatory proteins such as Vfr and RhlR itself, and also on the alternative
      sigma factor sigma(54). It is reported that rhlR expression is partially LasR
      independent under certain culture conditions and is strongly influenced by
      environmental factors.

PMID- 14600220
TI  - A novel type of DNA curvature present in a Clostridium perfringens ferredoxin
      gene: characterization and role in gene expression.
AB  - This study has revealed that a Clostridium perfringens ferredoxin gene (per-fdx)
      possesses a novel type of DNA curvature, which is formed by five phased A-tracts
      extending from upstream to downstream of the -35 region. The three A-tracts
      upstream of the promoter and the two within the promoter are located at the
      positions corresponding to A-tracts present in a C. perfringens phospholipase C
      gene (plc) and a Clostridium pasteurianum ferredoxin gene (pas-fdx),
      respectively. DNA fragments of the per-fdx, pas-fdx and plc genes (nucleotide
      positions -69 to +1 relative to the transcription initiation site) were fused to
      a chloramphenicol acetyltransferase reporter gene on a plasmid, pPSV, and their
      in vivo promoter activities were examined by assaying the chloramphenicol
      acetyltransferase activity of each C. perfringens transformant. Comparison of the
      three constructs showed that the order of promoter activity is, in descending
      order, per-fdx, pas-fdx and plc. Deletion of the three upstream A-tracts of the
      per-fdx gene drastically decreased the promoter activity, as demonstrated
      previously for the plc promoter. Substitution of the most downstream A-tract
      decreased the promoter activities of the per-fdx and pas-fdx genes. These results
      indicate that not only the phased A-tracts upstream of the promoter but also
      those within the promoter stimulate the promoter activity, and suggest that the
      high activity of the per-fdx promoter is due to the combined effects of these two
      types of A-tracts.

PMID- 14600221
TI  - Intron requirement for AFP gene expression in Trichoderma viride.
AB  - The 430 bp ORF of the Aspergillus giganteus antifungal protein (AFP) gene,
      containing two small introns, was fused between the promoter and the terminator
      of the Aspergillus nidulans trpC gene. The AFP gene in this vector produced
      detectable levels of spliced mRNA in Trichoderma viride. In contrast, in the same
      vector configuration, its 285 bp intronless derivative showed no accumulation of
      mRNA when transformed into T. viride. Such expression results were confirmed at
      the protein level. This fact demonstrated that the introns were required for AFP
      gene expression in T. viride. This is thought to be a novel phenomenon found in
      filamentous fungi. Although the mechanism of splicing in filamentous fungi might
      be similar to that in other eukaryotes, little is known of how it affects
      expression. This study suggests that the small introns in filamentous fungal
      genes may not only act as intervening elements, but may also play crucial roles
      in gene expression by affecting mRNA accumulation. Furthermore, it may provide
      new evidence for intron-dependent evolution.

PMID- 14600222
TI  - Cryptons: a group of tyrosine-recombinase-encoding DNA transposons from
      pathogenic fungi.
AB  - A new group of transposable elements, which the authors have named cryptons, was
      detected in several pathogenic fungi, including the basidiomycete Cryptococcus
      neoformans, and the ascomycetes Coccidioides posadasii and Histoplasma
      capsulatum. These elements are unlike any previously described transposons. An
      archetypal member of the group, crypton Cn1, is 4 kb in length and is present at
      a low but variable copy number in a variety of C. neoformans strains. It displays
      interstrain variations in its insertion sites, suggesting recent mobility. The
      internal region contains a long gene, interrupted by several introns. The product
      of this gene contains a putative tyrosine recombinase near its middle, and a
      region similar in sequence to the DNA-binding domains of several fungal
      transcription factors near its C-terminus. The element contains no long repeat
      sequences, but is bordered by short direct repeats which may have been produced
      by its insertion into the host genome by recombination. Many of the structural
      features of crypton Cn1 are conserved in the other known cryptons, suggesting
      that these elements represent the functional forms. The presence of cryptons in
      ascomycetes and basidiomycetes suggests that this is an ancient group of elements
      (>400 million years old). Sequence comparisons suggest that cryptons may be
      related to the DIRS1 and Ngaro1 groups of tyrosine-recombinase-encoding
      retrotransposons.

PMID- 14600223
TI  - Time series analysis demonstrates the absence of pulsatile hyphal growth.
AB  - Hyphal tip growth has been previously reported as pulsatile, defined as regularly
      alternating fast and slow rates of extension. The growth of pollen tubes, and
      hyphae of Neurospora crassa and Saprolegnia ferax were analysed using high
      spatial and temporal resolution. By using long (100-500 s) records of growth
      rate, sampled every second, it was possible to apply rigorous statistical
      analysis of the time series. As previously demonstrated, pollen tubes can show
      pulsatile growth, detectable with this system. In contrast, hyphal growth rates
      do not show any evidence of pulsatile growth; instead, growth rates appear to
      fluctuate randomly. It is concluded that pulsatile growth is not a common feature
      of hyphal tip growth.

PMID- 14600224
TI  - In situ localization of manganese peroxidase production in mycelial pellets of
      Phanerochaete chrysosporium.
AB  - The ultrastructure of Phanerochaete chrysosporium hyphae from pellets in
      submerged liquid cultures was investigated in order to learn more about the
      interrelation between fungal architecture and manganese peroxidase (MnP)
      production. At day 2 of cultivation, some subapical regions of hyphae in the
      outer and middle zones of the pellet initiated differentiation into intercalary
      thick-walled chlamydospore-like cells of about 10 micro m diameter. At the
      periphery of the cytoplasm of these cells, a large number of mitochondria and
      Golgi-like vesicles were observed. The sites of MnP production were localized at
      different stages of cultivation by an immunolabelling procedure. The immunomarker
      of MnP was mainly concentrated in the chlamydospore-like cells and principally
      distributed in Golgi-like vesicles located at the periphery of the cytoplasm. The
      apices of hyphae in the outer layer of the pellets were apparently minor sites of
      MnP production. Maximal MnP release into the culture supernatant coincided with
      apparent autolysis of the chlamydospore-like cells. Production of extracellular
      autolytic chitinase and protease coincided with the disappearance of these
      structures from the pellets. The chlamydospore-like cells observed in the
      mycelial pellets of P. chrysosporium could be metabolically active entities
      operating as an enzyme reservoir, delivering their content into the surrounding
      medium possibly by an enzyme-mediated autolytic process.

PMID- 14600225
TI  - Chitin scar breaks in aged Saccharomyces cerevisiae.
AB  - Ageing in budding yeast is not determined by chronological lifespan, but by the
      number of times an individual cell is capable of dividing, termed its replicative
      capacity. As cells age they are subject to characteristic cell surface changes.
      Saccharomyces cerevisiae reproduces asexually by budding and as a consequence of
      this process both mother and daughter cell retain chitinous scar tissue at the
      point of cytokinesis. Daughter cells exhibit a frail structure known as the birth
      scar, while mother cells display a more persistent bud scar. The number of bud
      scars present on the cell surface is directly related to the number of times a
      cell has divided and thus constitutes a biomarker for replicative cell age. It
      has been proposed that the birth scar may be subject to stretching caused by
      expansion of the daughter cell; however, no previous analysis of the effect of
      cell age on birth or bud scar size has been reported. This paper provides
      evidence that scar tissue expands with the cell during growth. It is postulated
      that symmetrically arranged breaks in the bud scar allow these rigid chitinous
      structures to expand without compromising cellular integrity.

PMID- 14600226
TI  - The 64 508 bp IncP-1beta antibiotic multiresistance plasmid pB10 isolated from a
      waste-water treatment plant provides evidence for recombination between members
      of different branches of the IncP-1beta group.
AB  - The complete 64508 bp nucleotide sequence of the IncP-1beta antibiotic-resistance
      plasmid pB10, which was isolated from a waste-water treatment plant in Germany
      and mediates resistance against the antimicrobial agents amoxicillin,
      streptomycin, sulfonamides and tetracycline and against mercury ions, was
      determined and analysed. A typical class 1 integron with completely conserved 5'
      and 3' segments is inserted between the tra and trb regions. The two mobile gene
      cassettes of this integron encode a beta-lactamase of the oxacillin-hydrolysing
      type (Oxa-2) and a gene product of unknown function (OrfE-like), respectively.
      The pB10-specific gene load present between the replication module (trfA1) and
      the origin of vegetative replication (oriV) is composed of four class II (Tn3
      family) transposable elements: (i). a Tn501-like mercury-resistance (mer)
      transposon downstream of the trfA1 gene, (ii). a truncated derivative of the
      widespread streptomycin-resistance transposon Tn5393c, (iii). the insertion
      sequence element IS1071 and (iv). a Tn1721-like transposon that contains the
      tetracycline-resistance genes tetA and tetR. A very similar Tn501-like mer
      transposon is present in the same target site of the IncP-1beta degradative
      plasmid pJP4 and the IncP-1beta resistance plasmid R906, suggesting that pB10,
      R906 and pJP4 are derivatives of a common ancestor. Interestingly, large parts of
      the predicted pB10 restriction map, except for the tetracycline-resistance
      determinant, are identical to that of R906. It thus appears that plasmid pB10
      acquired as many as five resistance genes via three transposons and one integron,
      which it may rapidly spread among bacterial populations given its high
      promiscuity. Comparison of the pB10 backbone DNA sequences with those of other
      sequenced IncP-1beta plasmids reveals a mosaic structure. While the conjugative
      transfer modules (trb and tra regions) and the replication module are very
      closely related to the corresponding segments of the IncP-1beta resistance
      plasmid R751 and even more similar to the IncP-1beta degradative plasmids pTSA
      and pADP-1, the stable inheritance operons klcAB-korC and kleAEF are most similar
      to those of the IncP-1beta resistance plasmid pB4, and clearly less similar to
      the other IncP-1beta plasmids. This suggests that IncP-1beta plasmids can undergo
      recombination in the environment, which may enhance plasmid diversity and
      bacterial adaptability.

PMID- 14600227
TI  - Foreign signal peptides can constitute a barrier to functional expression of
      periplasmic proteins in Haemophilus influenzae.
AB  - To study the periplasmic branch of iron (ferric ion) uptake systems in Gram
      negative bacteria, genetic reconstitution experiments were initiated in
      Haemophilus influenzae involving exchange of the periplasmic iron-binding
      protein. The expression of many of the heterologous periplasmic ferric-binding
      proteins (FbpAs) was quite limited. Transformation experiments with the fbpA gene
      from Neisseria gonorrhoeae yielded two colony sizes with different phenotypic
      characteristics. The small colonies contained the intact N. gonorrhoeae fbpA gene
      and were deficient in utilization of transferrin iron. The large colonies
      contained hybrid H. influenzae/N. gonorrhoeae fbpA genes, were proficient in
      transferrin iron utilization and had enhanced levels of expression of FbpA. These
      hybrid genes included several that encoded the mature N. gonorrhoeae FbpA with
      the H. influenzae signal peptide. To more fully evaluate the effect of foreign
      signal peptides, a series of hybrid genes were prepared that exchanged the signal
      peptides from H. influenzae FbpA, N. gonorrhoeae FbpA and the TEM-1 beta
      lactamase. The presence of the H. influenzae leader was required for functional
      expression of FbpAs and was shown to dramatically increase the level of beta
      lactamase activity.

PMID- 14600228
TI  - The role of lex2 in lipopolysaccharide biosynthesis in Haemophilus influenzae
      strains RM7004 and RM153.
AB  - The locus lex2, comprising lex2A and lex2B, contributes to the phase-variable
      expression of lipopolysaccharide (LPS) of Haemophilus influenzae and was found to
      be present in 74 % of strains investigated. lex2A contains 5'-GCAA repeats which
      vary in number from 4 to 46 copies between strains. The locus was cloned from the
      serotype b strains RM7004 and RM153 and showed >99 % nucleotide sequence identity
      between these strains and the published lex2 sequence. Disruption of the lex2B
      gene in strain RM7004 resulted in truncation of some LPS glycoforms, shown by gel
      fractionation, with only one glycoform reacting with a digalactoside-specific
      monoclonal antibody, 4C4, compared with four LPS glycoforms in the more elongated
      LPS of the parent strain. Mass spectrometry and NMR analyses of LPS from the
      lex2B mutant revealed loss of the terminal digalactoside as well as the second
      beta-glucose extending from the first heptose of the inner core. The authors
      conclude that Lex2B is the beta-(1-4)-glucosyltransferase that adds the second
      beta-glucose to the first beta-glucose as part of the oligosaccharide extension
      from the first heptose of the LPS of strain RM7004. Investigation of the
      expression of the lex2 locus indicated that the genes are co-transcribed and that
      both reading frames are required for addition of this second beta-glucose in a
      phase-variable manner.

PMID- 14600229
TI  - Genetic analysis of a plasmid encoding haemocin production in Haemophilus
      paragallinarum.
AB  - The full sequence of plasmid p250, isolated from Haemophilus paragallinarum
      strain HP250, has been obtained. The plasmid contains seven ORFs: a putative
      integrase, a putative replication protein (repB) and five ORFs similar to those
      from the haemocin (bacteriocin) hmcDCBAI operon from Haemophilus influenzae. Of
      19 other non-plasmid-containing H. paragallinarum strains screened (11 serovar
      reference strains and 8 field isolates), 17 strains produced haemocin and were
      resistant to killing by strain HP250. These strains, unlike strain HP250, have a
      chromosomally encoded haemocin operon. A number of other members of the family
      Pasteurellaceae were tested for haemocin sensitivity. Pasteurella avium,
      Pasteurella volantium and Pasteurella species A, all non-pathogenic bacteria
      found in the respiratory tract of chickens suffering from respiratory diseases,
      were sensitive to H. paragallinarum haemocin. However, amongst the pathogenic
      Pasteurellaceae, 50 % of P. multocida isolates and all five isolates of
      Pasteurella haemolytica tested were sensitive to the haemocin. Given the
      prevalence of haemocin production in H. paragallinarum strains, it may play a
      role in aiding colonization by inhibiting other Gram-negative bacteria that are
      associated with the respiratory tract in chickens. The origin of replication from
      plasmid p250 has been used to generate an Escherichia coli-H. paragallinarum
      shuttle vector which may be useful in genetically manipulating H. paragallinarum.

PMID- 14600230
TI  - The aquaporin gene aqpX of Brucella abortus is induced in hyperosmotic
      conditions.
AB  - An aquaporin gene (aqpX) was previously detected in the pathogenic bacterium
      Brucella abortus. Earlier studies showed that AqpX mediated rapid and large water
      fluxes in both directions in response to sudden osmotic up- or downshifts. Here,
      to study the role and the expression of the aqpX gene in B. abortus, an aqpX null
      mutant was constructed using an aqpX : : lacZ gene fusion. This mutant showed no
      significant difference in growth rate compared to the wild-type strain when grown
      in rich and minimal media, demonstrating that disruption of the aqpX gene was not
      lethal for B. abortus. The role of the B. abortus AqpX water channel was
      investigated by exposing the cells to hypo- and hyperosmolar conditions. While in
      hyperosmolar environments the growth rate of the knockout mutant was not
      affected, in hypo-osmolar conditions this mutant showed reduced viability after
      50 h of growth. beta-Galactosidase assays and RT-PCR revealed that aqpX gene
      expression and the amount of aqpX mRNA were markedly increased in hyperosmolar
      conditions. Moreover, B. abortus aqpX expression levels were enhanced during the
      mid-exponential phase of growth. These results indicated that the expression of
      aqpX was regulated during the growth curve and induced in hyperosmolar
      conditions. This report is believed to be the first example of the induction of a
      bacterial aquaporin in hypertonic conditions.

PMID- 14600231
TI  - Biosynthetic specificity of the rhamnosyltransferase gene of Mycobacterium avium
      serovar 2 as determined by allelic exchange mutagenesis.
AB  - In prior studies, through recombinant expression in Mycobacterium smegmatis, the
      rtfA gene of Mycobacterium avium was shown to encode a rhamnosyltransferase that
      catalyses the addition of rhamnose (Rha) to the 6-deoxytalose of serovar 2
      specific glycopeptidolipid (GPL). Whether RtfA also catalyses the transfer of Rha
      to the alaninol of the lipopeptide core is unknown. An isogenic rtfA mutant of M.
      avium serovar 2 strain TMC724 was derived using a novel allelic exchange
      mutagenesis system utilizing a multicopy plasmid that contained the katG gene of
      Mycobacterium bovis and the gene encoding green fluorescent protein (gfp).
      Overexpression of KatG in M. avium resulted in increased susceptibility to
      isoniazid, thus providing counter-selection by enriching for clones that had lost
      plasmid DNA. Plasmid loss was confirmed by screening for gfp-negative clones to
      select putative allelic exchange mutants. Two exchange mutants were created,
      confirmed by Southern hybridization, and demonstrated loss of serovar 2-specific
      GPL by thin-layer chromatography (TLC). Gas chromatography of alditol acetate
      derivatives revealed the loss of Rha and the terminal 2,3-O-Me-fucose and
      preservation of 3-O-Me-Rha and 3,4-O-Me-Rha substituents at the terminal alaninol
      of the lipopeptide core. Complementation of rtfA in trans through an integrative
      plasmid restored serovar 2-specific GPL expression identical to wild-type TMC724.
      This result shows that rtfA encodes an enzyme responsible only for the transfer
      of Rha to the serovar 2-specific oligosaccharide and provides a system of allelic
      exchange for M. avium as a tool for future genetic studies involving this
      species.

PMID- 14600232
TI  - Different susceptibility of two animal species infected with isogenic mutants of
      Mycobacterium bovis identifies phoT as having roles in tuberculosis virulence and
      phosphate transport.
AB  - The Mycobacterium tuberculosis complex includes Mycobacterium bovis, which causes
      tuberculosis in most mammals, including humans. In previous work, it was shown
      that M. bovis ATCC 35721 has a mutation in its principal sigma factor gene, sigA,
      causing a single amino acid change affecting binding of SigA with the accessory
      transcription factor WhiB3. ATCC 35721 is avirulent when inoculated
      subcutaneously into guinea pigs but can be restored to virulence by integration
      of wild-type sigA to produce M. bovis WAg320. Subsequently, it was surprising to
      discover that WAg320 was not virulent when inoculated intratracheally into the
      Australian brushtail possum (Trichosurus vulpecula), a marsupial that is normally
      very susceptible to infection with M. bovis. In this study, an in vivo
      complementation approach was used with ATCC 35721 to produce M. bovis WAg322,
      which was virulent in possums, and to identify the virulence-restoring gene,
      phoT. There are two point deletions in the phoT gene of ATCC 35721 causing
      frameshift inactivation, one of which is also in the phoT of BCG. Knockout of
      phoT from ATCC 35723, a virulent strain of M. bovis, produced M. bovis WAg758,
      which was avirulent in both guinea pigs and possums, confirming that phoT is a
      virulence gene. The effect on virulence of mode of infection versus animal
      species susceptibility was investigated by inoculating all the above strains by
      aerosol into guinea pigs and mice and comparing these to the earlier results.
      Characterization of PhoT indicated that it plays a role in phosphate uptake at
      low phosphate concentrations. At least in vitro, this role requires the presence
      of a wild-type sigA gene and appears separate from the ability of phoT to restore
      virulence to ATCC 35721. This study shows the advantages of using different
      animal models as tools for the molecular biological investigation of tuberculosis
      virulence.

PMID- 14600233
TI  - Koch's bacillus - a look at the first isolate of Mycobacterium tuberculosis from
      a modern perspective.
AB  - Using molecular methods the authors have studied mycobacterial DNA taken from a
      19th century victim of tuberculosis. This was the case from which Robert Koch
      first isolated and cultured the organism responsible for tuberculosis. The
      mycobacteria were preserved within five glass culture tubes as abundant bacterial
      colonies on slopes of a gelatinous culture medium of unknown composition.
      Originally presented by Koch to surgical laryngologist Walter Jobson Horne in
      London in 1901, the relic has, since 1983, been in the care of the Royal College
      of Surgeons of England. Light and electron microscopy established the presence of
      acid-fast mycobacteria but showed that morphological preservation was generally
      poor. Eleven different genomic loci were successfully amplified by PCR. This
      series of experiments confirmed that the organisms were indeed Mycobacterium
      tuberculosis and further showed that the original strain was in evolutionary
      terms similar to 'modern' isolates, having undergone the TB D1 deletion. Attempts
      to determine the genotypic group of the isolate were only partially successful,
      due in part to the degraded nature of the DNA and possibly also to a truncation
      in the katG gene, which formed part of the classification scheme. Spoligotyping
      resulted in amplification of DR spacers consistent with M. tuberculosis but with
      discrepancies between independent extracts, stressing the limitations of this
      typing method when applied to poorly preserved material.

PMID- 14600234
TI  - A Caenorhabditis elegans model of Yersinia infection: biofilm formation on a
      biotic surface.
AB  - To investigate Yersinia pathogenicity and the evolutionary divergence of the
      genus, the effect of pathogenic yersiniae on the model organism Caenorhabditis
      elegans was studied. Three strains of Yersinia pestis, including a strain lacking
      pMT1, caused blockage and death of C. elegans; one strain, lacking the haemin
      storage (hms) locus, caused no effect. Similarly, 15 strains of Yersinia
      enterocolitica caused no effect. Strains of Yersinia pseudotuberculosis showed
      different levels of pathogenicity. The majority of strains (76 %) caused no
      discernible effect; 5 % caused a weak infection, 9.5 % an intermediate infection,
      and 9.5 % a severe infection. There was no consistent relationship between
      serotype and severity of infection; nor was there any relationship between
      strains causing infection of C. elegans and those able to form a biofilm on an
      abiotic surface. Electron microscope and cytochemical examination of infected
      worms indicated that the infection phenotype is a result of biofilm formation on
      the head of the worm. Seven transposon mutants of Y. pseudotuberculosis strain
      YPIII pIB1 were completely or partially attenuated; mutated genes included genes
      encoding proteins involved in haemin storage and lipopolysaccharide biosynthesis.
      A screen of 15 defined C. elegans mutants identified four where mutation caused
      (complete) resistance to infection by Y. pseudotuberculosis YPIII pIB1. These
      mutants, srf-2, srf-3, srf-5 and the dauer pathway gene daf-1, also exhibit
      altered binding of lectins to the nematode surface. This suggests that biofilm
      formation on a biotic surface is an interactive process involving both bacterial
      and invertebrate control mechanisms.

PMID- 14600235
TI  - Proteus mirabilis fimbriae (PMF) are important for both bladder and kidney
      colonization in mice.
AB  - Proteus mirabilis expresses different types of fimbriae simultaneously. Several
      fimbrial types have been described and their role in the colonization of the
      urinary tract is under study. Previously, P. mirabilis fimbriae (PMF) have been
      shown to be associated with bacterial colonization of the lower urinary tract but
      not of the kidneys. In this study, a pmfA mutant was generated and used in
      several in vivo and in vitro studies. Two different urinary tract infection
      models in the mouse and two in vitro assays of bacterial adhesion to
      uroepithelial cells were performed. Expression of PmfA in a collection of P.
      mirabilis strains of different sources was also assessed. The results shown here
      indicate that PMF are involved in both bladder and kidney colonization by P.
      mirabilis and that these fimbriae are widely distributed among P. mirabilis
      isolates from different origins since all strains tested expressed PmfA.

PMID- 14600236
TI  - Inhibition of adhesion of yeasts and bacteria by poly(ethylene oxide)-brushes on
      glass in a parallel plate flow chamber.
AB  - Poly(ethylene oxide) (PEO)-brushes are generally recognized as protein-repellent
      surfaces, and although a role in discouraging microbial adhesion has been
      established for some strains and species, no study exists on the effects of PEO
      brushes on a large variety of bacterial and yeast strains. In this paper, a PEO
      brush has been covalently attached to glass and silica by reaction in a polymer
      melt. Subsequently, the presence of a PEO-brush was demonstrated using contact
      angle measurements, X-ray photoelectron spectroscopy and ellipsometry. For five
      bacterial (Staphylococcus epidermidis, Staphylococcus aureus, Streptococcus
      salivarius, Escherichia coli and Pseudomonas aeruginosa) and two yeast strains
      (Candida albicans and Candida tropicalis), adhesion to PEO-brushes was compared
      with adhesion to bare glass in a parallel plate flow chamber. The initial
      deposition rates of Sta. epidermidis, Sta. aureus and Str. salivarius to glass
      were relatively high, between 2400 and 2600 cm(-2) s(-1), while E. coli and P.
      aeruginosa deposited much more slowly. The initial deposition rates of the yeasts
      to glass were 144 and 444 cm(-2) s(-1) for C. albicans GB 1/2 and C. tropicalis
      GB 9/9, respectively. Coating of the glass surface with a PEO-brush yielded more
      than 98 % reduction in bacterial adhesion, although for the more hydrophobic P.
      aeruginosa a smaller reduction was observed. For both yeast species adhesion
      suppression was less effective than for the bacteria and here too the more
      hydrophobic C. tropicalis showed less reduction than the more hydrophilic C.
      albicans. The PEO-brush had a thickness of 22 nm in water, as inferred from
      ellipsometry. Assuming that on bare glass the adhered micro-organisms are
      positioned only a few nanometers away from the surface and that the brush keeps
      them at a distance of 22 nm, it is calculated that the brush yields a sevenfold
      attenuation of the Lifshitz-Van der Waals attraction to the surface between the
      micro-organisms and the surface. Decreased Lifshitz-van der Waals attraction may
      be responsible for the suppression of the microbial adhesion observed.

PMID- 14600237
TI  - Sigma(B)-dependent expression patterns of compatible solute transporter genes
      opuCA and lmo1421 and the conjugated bile salt hydrolase gene bsh in Listeria
      monocytogenes.
AB  - Listeria monocytogenes is a food-borne pathogen that can persist and grow under a
      wide variety of environmental conditions including low pH and high osmolarity.
      The alternative sigma factor sigma(B) contributes to L. monocytogenes survival
      under extreme conditions. The purpose of this study was to identify and confirm
      specific sigma(B)-dependent genes in L. monocytogenes and to characterize their
      expression patterns under various stress conditions. opuCA, lmo1421 and bsh were
      identified as putative sigma(B)-dependent genes based on the presence of a
      predicted sigma(B)-dependent promoter sequence upstream of each gene. opuCA and
      lmo1421 encode known and putative compatible solute transporter proteins,
      respectively, and bsh encodes a conjugated bile salt hydrolase (BSH). Reporter
      fusions and semi-quantitative RT-PCR techniques were used to confirm sigma(B)
      dependent regulation of these stress-response genes and to determine their
      expression patterns in response to environmental stresses. RT-PCR demonstrated
      that opuCA, lmo1421 and bsh transcript levels are reduced in stationary-phase L.
      monocytogenes deltasigB cells relative to levels present in wild-type cells.
      Furthermore, BSH activity is abolished in a L. monocytogenes deltasigB strain. RT
      PCR confirmed growth-phase-dependent expression of opuCA, with highest levels of
      expression in stationary-phase cells. The L. monocytogenes wild-type strain
      exhibited two- and threefold induction of opuCA expression and seven- and
      fivefold induction of lmo1421 expression following 10 and 15 min exposure to 0.5
      M KCl, respectively, as determined by RT-PCR, suggesting rapid induction of
      sigma(B) activity in exponential-phase L. monocytogenes upon exposure to salt
      stress. Single-copy chromosomal opuCA-gus reporter fusions also showed
      significant induction of opuCA expression following exposure of exponential-phase
      cells to increased salt concentrations (0.5 M NaCl or 0.5 M KCl). In conjunction
      with recent findings that indicate a role for opuCA and bsh in L. monocytogenes
      virulence, the data presented here provide further evidence of specific sigma(B)
      mediated contributions to both environmental stress resistance and intra-host
      survival in L. monocytogenes.

PMID- 14600238
TI  - An increase in the level of 2-oxoglutarate promotes heterocyst development in the
      cyanobacterium Anabaena sp. strain PCC 7120.
AB  - In the filamentous cyanobacterium Anabaena sp. strain PCC 7120, a starvation of
      combined nitrogen induces differentiation of heterocysts, cells specialized in
      nitrogen fixation. How do filaments perceive the limitation of the source of
      combined nitrogen, and what determines the proportion of heterocysts? In
      cyanobacteria, 2-oxoglutarate provides a carbon skeleton for the incorporation of
      inorganic nitrogen. Recently, it has been proposed that the concentration of 2
      oxoglutarate reflects the nitrogen status in cyanobacteria. To investigate the
      effect of 2-oxoglutarate on heterocyst development, a heterologous gene encoding
      a 2-oxoglutarate permease under the control of a regulated promoter was expressed
      in Anabaena sp. PCC 7120. The increase of 2-oxoglutarate within cells can trigger
      heterocyst differentiation in a subpopulation of filaments even in the presence
      of nitrate. In the absence of a source of combined nitrogen, it can increase
      heterocyst frequency, advance the timing of commitment to heterocyst development
      and further increase the proportion of heterocysts in a patS mutant. Here, it is
      proposed that the intracellular concentration of 2-oxoglutarate is involved in
      the determination of the proportion of the two cell types according to the
      carbon/nitrogen status of the filament.

PMID- 14600239
TI  - 3- and 4-alkylphenol degradation pathway in Pseudomonas sp. strain KL28: genetic
      organization of the lap gene cluster and substrate specificities of phenol
      hydroxylase and catechol 2,3-dioxygenase.
AB  - The enzymes and genes responsible for the catabolism of higher alkylphenols have
      not been characterized in aerobic bacteria. Pseudomonas sp. strain KL28 can
      utilize a wide range of alkylphenols, which include the 4-n-alkylphenols (C(1)
      C(5)). The genes, designated as lap (for long-chain alkylphenols), encoding
      enzymes for the catabolic pathway were cloned from chromosomal DNA and sequenced.
      The lap genes are located in a 13.2 kb region with 14 ORFs in the order
      lapRBKLMNOPCEHIFG and with the same transcriptional orientation. The lapR gene is
      transcribed independently and encodes a member of the XylR/DmpR positive
      transcriptional regulators. lapB, the first gene in the lap operon, encodes
      catechol 2,3-dioxygenase (C23O). The lapKLMNOP and lapCEHIFG genes encode a
      multicomponent phenol hydroxylase (mPH) and enzymes that degrade derivatives of 2
      hydroxymuconic semialdehyde (HMS) to TCA cycle intermediates, respectively. The
      P(lapB) promoter contains motifs at positions -24(GG) and -12(GC) which are
      typically found in sigma(54)-dependent promoters. A promoter assay using a
      P(lapB) : : gfp transcriptional fusion plasmid showed that lapB promoter activity
      is inducible and that it responds to a wide range of (alkyl)phenols. The
      structural genes encoding enzymes required for this catabolism are similar (42-69
      %) to those encoded on a catabolic pVI150 plasmid from an archetypal phenol
      degrader, Pseudomonas sp. CF600. However, the lap locus does not include genes
      encoding HMS hydrolase and ferredoxin. The latter is known to be functionally
      associated with C23O for use of 4-alkylcatechols as substrates. The arrangement
      of the lap catabolic genes is not commonly found in other meta-cleavage operons.
      Substrate specificity studies show that mPH preferentially oxidizes 3- and 4
      alkylphenols to 4-alkylcatechols. C23O preferentially oxidizes 4-alkylcatechols
      via proximal (2,3) cleavage. This indicates that these two key enzymes have
      unique substrate preferences and lead to the establishment of the initial steps
      of the lap pathway in strain KL28.

PMID- 14600240
TI  - Characterization of a soil-derived bacterial consortium degrading 4
      chloroaniline.
AB  - A bacterial consortium comprising four different species was isolated from an
      Indonesian agricultural soil using a mixture of aniline and 4-chloroaniline (4CA)
      as principal carbon sources. The four species were identified as Chryseobacterium
      indologenes SB1, Comamonas testosteroni SB2, Pseudomonas corrugata SB4 and
      Stenotrophomonas maltophilia SB5. Growth studies on aniline and 4CA as single and
      mixed substrates demonstrated that the bacteria preferred to grow on and utilize
      aniline rather than 4CA, although both compounds were eventually depleted from
      the culture supernatant. However, despite 100 % disappearance of the parent
      substrates, the degradation of 4CA was always characterized by incomplete
      dechlorination and 4-chlorocatechol accumulation. This result suggests that
      further degradation of 4-chlorocatechol may be the rate-limiting step in the
      metabolism of 4CA by the bacterial consortium. HPLC-UV analysis showed that 4
      chlorocatechol was further degraded via an ortho-cleavage pathway by the
      bacterial consortium. This hypothesis was supported by the results from enzyme
      assays of the crude cell extract of the consortium revealing catechol 1,2
      dioxygenase activity which converted catechol and 4-chlorocatechol to cis,cis
      muconic acid and 3-chloro-cis,cis-muconic acid respectively. However, the enzyme
      had a much higher conversion rate for catechol [156 U (g protein)(-1)] than for 4
      chlorocatechol [17.2 U (g protein)(-1)], indicating preference for non
      chlorinated substrates. Members of the bacterial consortium were also
      characterized individually. All isolates were able to assimilate aniline. P.
      corrugata SB4 was able to grow on 4CA solely, while S. maltophilia SB5 was able
      to grow on 4-chlorocatechol. These results suggest that the degradation of 4CA in
      the presence of aniline by the bacterial consortium was a result of interspecies
      interactions.

PMID- 14600241
TI  - Ammonium utilization in Bacillus subtilis: transport and regulatory functions of
      NrgA and NrgB.
AB  - Bacillus subtilis uses glutamine as the best source of nitrogen. In the absence
      of glutamine, alternative nitrogen sources such as ammonium can be used. Ammonium
      utilization involves the uptake of the gas or the ammonium ion, the synthesis of
      glutamine by the glutamine synthetase and the recycling of the glutamate by the
      glutamate synthase. In this work, ammonium transport in B. subtilis was studied.
      At high ammonium concentrations, a large fraction of the ammonium is present as
      ammonia, which may enter the cell via diffusion. In contrast, the ammonium
      transporter NrgA is required for ammonium utilization at low concentrations or at
      low pH values when the equilibrium between uncharged ammonia and the ammonium ion
      is shifted towards ammonium. Moreover, a functional NrgA is essential for the
      transport of the ammonium analogue methylammonium. NrgA is encoded in the nrgAB
      operon. The product of the second gene, NrgB, is a member of the PII family of
      regulatory proteins. In contrast to PII proteins from other organisms, there is
      no indication for a covalent modification of NrgB in response to the nitrogen
      supply of the cell. It is demonstrated here that NrgB is localized at the
      membrane, most likely in association with the ammonium transporter NrgA. The
      presence of a functional NrgB is required for full-level expression of the nrgAB
      operon in response to nitrogen limitation, suggesting that NrgB might relay the
      information on ammonium availability to downstream regulatory factors and thus
      fine-tune their activity.

PMID- 14600242
TI  - An aberrant protein synthesis activity is linked with antibiotic overproduction
      in rpsL mutants of Streptomyces coelicolor A3(2).
AB  - Certain mutations in the rpsL gene (encoding the ribosomal protein S12) activate
      or enhance antibiotic production in various bacteria. K88E and P91S rpsL mutants
      of Streptomyces coelicolor A3(2), with an enhanced actinorhodin production, were
      found to exhibit an aberrant protein synthesis activity. While a high level of
      this activity (as determined by the incorporation of labelled leucine) was
      detected at the late stationary phase in the mutants, it decreased with age of
      the cells in the wild-type strain. In addition, the aberrant protein synthesis
      was particularly pronounced when cells were subjected to amino acid shift-down,
      and was independent of their ability to accumulate ppGpp. Ribosomes of K88E and
      P91S mutants displayed an increased accuracy in protein synthesis as demonstrated
      by the poly(U)-directed cell-free translation system, but so did K43N, K43T, K43R
      and K88R mutants, which were streptomycin resistant but showed no effect on
      actinorhodin production. This eliminates the possibility that the increased
      accuracy level is a cause of the antibiotic overproduction in the K88E and P91S
      mutants. The K88E and P91S mutant ribosomes exhibited an increased stability of
      the 70S complex under low concentrations of magnesium. The authors propose that
      the aberrant activation of protein synthesis caused by the increased stability of
      the ribosome is responsible for the remarkable enhancement of antibiotic
      production in the K88E and P91S mutants.

PMID- 14600243
TI  - Tetra-amino-acid tandem repeats are involved in HsdS complementation in type IC
      restriction-modification systems.
AB  - All known type I restriction and modification (R-M) systems of Escherichia coli
      and Salmonella enterica belong to one of four discrete families: type IA, IB, IC
      or ID. The classification of type I systems from a wide range of other genera is
      mainly based on complementation and molecular evidence derived from the
      comparison of the amino acid similarity of the corresponding subunits. This
      affiliation was seldom based on the strictest requirement for membership of a
      family, which depends on relatedness as demonstrated by complementation tests.
      This paper presents data indicating that the type I NgoAV R-M system from
      Neisseria gonorrhoeae, despite the very high identity of HsdM and HsdR subunits
      with members of the type IC family, does not show complementation with E. coli
      type IC R-M systems. Sequence analysis of the HsdS subunit of several different
      potential type IC R-M systems shows that the presence of different tetra-amino
      acid sequence repeats, e.g. TAEL, LEAT, SEAL, TSEL, is characteristic for type IC
      R-M systems encoded by distantly related bacteria. The other regions of the HsdS
      subunits potentially responsible for subunit interaction are also different
      between a group of distantly related bacteria, but show high similarity within
      these bacteria. Complementation between the NgoAV R-M system and members of the
      EcoR124 R-M family can be restored by changing the tetra-amino-acid repeat within
      the HsdS subunit. The authors propose that the type IC family of R-M systems
      could consist of several complementation subgroups whose specificity would depend
      on differences in the conserved regions of the HsdS polypeptide.

PMID- 14600244
TI  - (De)regulation of key enzyme steps in the shikimate pathway and phenylalanine
      specific pathway of the actinomycete Amycolatopsis methanolica.
AB  - Prephenate dehydratase (PDT), chorismate mutase (CM) and 3-deoxy-D-arabino-7
      heptulosonate 7-phosphate (DAHP) synthase are key regulatory enzymes in aromatic
      amino acid biosynthesis in the actinomycete Amycolatopsis methanolica.
      Deregulated, feedback-control-resistant mutants were isolated by incubation of A.
      methanolica on glucose mineral agar containing the toxic analogue p-fluoro-DL
      phenylalanine (pFPhe). Several of these mutants had completely lost PDT
      sensitivity to Phe inhibition and Tyr activation. Mutant characterization yielded
      new information about PDT amino acid residues involved in Phe and Tyr effector
      binding sites. A. methanolica wild-type cells grown on glucose mineral medium
      normally possess a bifunctional CM/DAHP synthase protein complex (with DS1, a
      plant-type DAHP synthase). The CM activity of this protein complex is feedback
      inhibited by Tyr and Phe, while DS1 activity is mainly inhibited by Trp.
      Isolation of pFPhe-resistant mutants yielded two feedback-inhibition-resistant CM
      mutants. These were characterized as regulatory mutants, derepressed in (a)
      synthesis of CM, now occurring as an abundant, feedback-inhibition-resistant,
      separate protein, and (b) synthesis of an alternative DAHP synthase (DS2, an E.
      coli-type DAHP synthase), only inhibited by Tyr and Trp. DS1 and DS2 thus are
      well integrated in A. methanolica primary metabolism: DS1 and CM form a protein
      complex, which stimulates CM activity and renders it sensitive to feedback
      inhibition by Phe and Tyr. Synthesis of CM and DS2 proteins appears to be
      controlled co-ordinately, sensitive to Phe-mediated feedback repression.

PMID- 14600245
TI  - Characterization of the LlaCI methyltransferase from Lactococcus lactis subsp.
      cremoris W15 provides new insights into the biology of type II restriction
      modification systems.
AB  - The gene encoding the LlaCI methyltransferase (M.LlaCI) from Lactococcus lactis
      subsp. cremoris W15 was overexpressed in Escherichia coli. The enzyme was
      purified to apparent homogeneity using three consecutive steps of chromatography
      on phosphocellulose, blue-agarose and Superose 12HR, yielding a protein of M(r)
      31 300+/-1000 under denaturing conditions. The exact position of the start codon
      AUG was determined by protein microsequencing. This enzyme recognizes the
      specific palindromic sequence 5'-AAGCTT-3'. Purified M.LlaCI was characterized.
      Unlike many other methyltransferases, M.LlaCI exists in solution predominantly as
      a dimer. It modifies the first adenine residue at the 5' end of the specific
      sequence to N(6)-methyladenine and thus is functionally identical to the
      corresponding methyltransferases of the HindIII (Haemophilus influenzae Rd) and
      EcoVIII (Escherichia coli E1585-68) restriction-modification systems. This is
      reflected in the identity of M.LlaCI with M.HindIII and M.EcoVIII noted at the
      amino acid sequence level (50 % and 62 %, respectively) and in the presence of
      nine sequence motifs conserved among N(6)-adenine beta-class methyltransferases.
      However, polyclonal antibodies raised against M.EcoVIII cross-reacted with
      M.LlaCI but not with M.HindIII. Restriction endonucleases require Mg(2+) for
      phosphodiester bond cleavage. Mg(2+) was shown to be a strong inhibitor of the
      M.LlaCI enzyme and its isospecific homologues. This observation suggests that
      sensitivity of the M.LlaCI to Mg(2+) may strengthen the restriction activity of
      the cognate endonuclease in the bacterial cell. Other biological implications of
      this finding are also discussed.

PMID- 14600246
TI  - Basal signaling activity of mu opioid receptor in mouse brain: role in narcotic
      dependence.
AB  - Narcotic analgesics cause addiction by poorly understood mechanisms, involving mu
      opoid receptor (MOR). Previous cell culture studies have demonstrated significant
      basal, spontaneous MOR signaling activity, but its relevance to narcotic
      addiction remained unclear. In this study, we tested basal MOR-signaling activity
      in brain tissue from untreated and morphine-pretreated mice, in comparison to
      antagonist-induced withdrawal in morphine-dependent mice. Using guanosine 5'-O-(3
      [(35)S]thio)triphosphate ([(35)S]GTP gamma S) binding and adenylyl cyclase
      activity assay in brain homogenates, we demonstrated that morphine pretreatment
      of mice enhanced basal MOR signaling in mouse brain homogenates and, moreover,
      caused persistent changes in the effects of naloxone and naltrexone, antagonists
      that elicit severe withdrawal in dependent subjects. Naloxone and naltrexone
      suppressed basal [(35)S]GTP gamma S binding (acting as "inverse agonists") only
      after morphine pretreatment, but not in drug-naive animals. Moreover, naloxone
      and naltrexone stimulated adenylyl cyclase activity in striatum homogenates only
      after morphine pretreatment, by reversing the inhibitory effects of basal MOR
      activity. After cessation of morphine treatment, the time course of inverse
      naloxone effects on basal MOR signaling was similar to the time course of
      naltrexone-stimulated narcotic withdrawal over several days. The neutral
      antagonist 6 beta-naltrexol blocked MOR activation without affecting basal
      signaling (G protein coupling and adenylyl cyclase regulation) and also elicited
      substantially less severe withdrawal. These results demonstrate long-lasting
      regulation of basal MOR signaling as a potential factor in narcotic dependence.

PMID- 14600247
TI  - Role of the heme oxygenases in abnormalities of the mesenteric circulation in
      cirrhotic rats.
AB  - Carbon monoxide (CO), a product of heme metabolism by heme-oxygenase (HO), has
      biological actions similar to those of nitric oxide (NO). The role of CO in
      decreasing vascular responses to constrictor agents produced by experimental
      cirrhosis induced by carbon tetrachloride was evaluated before and after
      inhibition of HO with tin-mesoporphyrin (SnMP) in the perfused superior
      mesenteric vasculature (SMV) of cirrhotic and normal rats and in normal rats
      transfected with the human HO-1 (HHO-1) gene. Perfusion pressure and
      vasoconstrictor responses of the SMV to KCl, phenylephrine (PE), and endothelin-1
      (ET-1) were decreased in cirrhotic rats. SnMP increased SMV perfusion pressure
      and restored the constrictor responses of the SMV to KCl, PE, and ET-1 in
      cirrhotic rats. The relative roles of NO and CO in producing hyporeactivity of
      the SMV to PE in cirrhotic rats were examined. Vasoconstrictor responses to PE
      were successively augmented by stepwise inhibition of CO and NO production,
      suggesting a complementary role for these gases in the regulation of reactivity
      of the SMV. Expression of constitutive but not of inducible HO (HO-1) was
      increased in the SMV of cirrhotic rats as was HO activity. Administration of
      adenovirus containing HHO-1 gene produced detection of HHO-1 RNA and increased HO
      activity in the SMV within 7 days. Rats transfected with HO-1 demonstrated
      reduction in both perfusion pressure and vasoconstrictor responses to PE in the
      SMV. We propose that HO is an essential component in mechanisms that modulate
      reactivity of the mesenteric circulation in experimental hepatic cirrhosis in
      rats.

PMID- 14600248
TI  - Activation of G-proteins by morphine and codeine congeners: insights to the
      relevance of O- and N-demethylated metabolites at mu- and delta-opioid receptors.
AB  - Phenotypic differences in analgesic sensitivity to codeine (3-methoxymorphine)
      results from polymorphisms in cytochrome P450-2D6, which catalyzes O
      demethylation of codeine to morphine. However, O-demethylation reportedly is not
      required for analgesic activity of the 7,8-saturated codeine congeners
      dihydrocodeine, hydrocodone, and oxycodone. This study determined the potency and
      efficacy of these compounds and their demethylated derivatives to stimulate mu-
      and delta-opioid receptor-mediated G-protein activation using agonist-stimulated
      guanosine 5'-O-(3-[(35)S]thio)triphosphate ([(35)S]GTP gamma S) binding. Results
      showed that 7,8-saturated codeine congeners were more efficacious than codeine in
      activating mu-receptors, but only dihydrocodeine was more efficacious at delta
      receptors. Hydrocodone and oxycodone were approximately 10-fold more potent than
      codeine and dihydrocodeine at either receptor. Morphine-like compounds with a 3
      hydroxy group were approximately 30- to 100-fold more potent than their 3-methoxy
      analogs at the mu-receptor, and these compounds generally exhibited greater
      efficacy (e.g., morphine produced 2-fold greater maximal stimulation than
      codeine). Removal of the N-methyl group did not affect efficacy or potency of
      codeine congeners to activate mu-receptors, whereas this modification generally
      increased efficacy but decreased potency of morphine congeners. At the delta
      receptor, morphine congeners showed greater potency and structure-dependent
      differences in efficacy compared with codeine congeners, whereas removal of the N
      methyl group had effects similar to those observed at the mu-receptor. These
      results demonstrate that 7,8-saturated codeine congeners are more efficacious
      than codeine, which may explain their lack of requirement for 3-O-demethylation
      in vivo. Nonetheless, because all 7,8-saturated codeine congeners were
      significantly less potent than their morphine derivatives, further research is
      needed to understand the relationship between metabolism and in vivo activity of
      these compounds.

PMID- 14600249
TI  - Adenosine tetraphosphate, Ap4, a physiological regulator of intraocular pressure
      in normotensive rabbit eyes.
AB  - Adenosine 5' tetraphosphate, Ap(4), is a natural nucleotide present in many
      biological systems. This nucleotide has been found as a constituent of the
      nucleotide pool present in the aqueous humor of New Zealand rabbits. HPLC
      analysis confirmed its identity and calculated its concentration levels to be 197
      +/- 21 nM. When applied topically to the rabbit eyes, this mononucleotide
      produced a reduction in the intraocular pressure, which was dose-dependent. The
      pD(2) value calculated from the dose-response curve was 7.28 +/- 0.47, which is
      equivalent to 52.48 nM. The time course of such intraocular pressure reduction
      presented a maximal decrease of IOP to 75.1 +/- 2.3% compared with the vehicle
      control value (100%), and the effect lasted for more than 2 h. Cross
      desensitization studies demonstrated that Ap(4) effect was mediated via a P2X
      receptor in this system. P2 receptor antagonists suramin, pyridoxal phosphate 6
      azophenyl-2',4'-disulfonic acid (PPADS), and reactive blue 2 (RB-2) showed that
      only the latter was able to revert the effect of Ap(4). Antagonists of
      adrenoceptors and cholinoceptors were able to partially reverse the effect of
      this nucleotide; this might indicate a connection with the neural mechanisms that
      control the intraocular pressure.

PMID- 14600250
TI  - Induction of human CYP2C9 by rifampicin, hyperforin, and phenobarbital is
      mediated by the pregnane X receptor.
AB  - Human CYP2C9 is important in the metabolism of numerous clinically used drugs
      such as the anticoagulant warfarin, the anticonvulsant phenytoin, antidiabetic
      drugs such as tolbutamide and glipizide, the hypertensive agent losartan, and
      numerous nonsteroidal anti-inflammatory drugs. Several studies have reported that
      certain drugs such as rifampicin and phenobarbital induce CYP2C9, but the
      molecular basis for this induction remains unknown. In the present study, we
      demonstrate that the human pregnane X receptor (hPXR) mediates induction of
      CYP2C9 by the prototype drugs rifampicin, hyperforin (found in St. John's Wart),
      and phenobarbital. Deletion and mutagenesis studies with luciferase reporter
      constructs showed that a functional PXR-responsive element located -1839/-1824
      base pairs upstream from the translation start site was the primary binding site
      mediating the rifampicin induction of CYP2C9. This site was previously described
      as a constitutive androstane receptor-responsive element (CAR-RE). Mutational
      analysis of 3- and 12-kilobase CYP2C9 promoter fragments indicated that this
      proximal binding site was essential for rifampicin inducibility, although a
      cooperative effect could be attributed to a second CAR-RE located at -2899/-2883.
      In summary, we have demonstrated rifampicin induction of CYP2C9 promoter
      constructs that is consistent with the magnitude of induction of CYP2C9 protein
      and mRNA reported in vivo and in primary human hepatocytes, and we have
      identified the cis-element essential for this response. This is the first report
      to demonstrate that the nuclear receptor PXR mediates induction of CYP2C9 with
      rifampicin, phenobarbital, and hyperforin.

PMID- 14600252
TI  - Chronic prenatal ethanol exposure impairs conditioned responding and enhances
      GABA release in the hippocampus of the adult guinea pig.
AB  - In this study, we assessed the effects of chronic prenatal ethanol exposure
      (CPEE) on spatial navigation in the water maze, conditioned responding using food
      reinforced lever pressing, and amino acid neurotransmitter release from the
      hippocampus of the adult guinea pig. Pregnant guinea pigs were treated with
      ethanol (3 g/kg of maternal body weight/day), isocaloric-sucrose/pair-feeding, or
      water throughout gestation. Adult offspring were trained in two-lever operant
      chambers to respond for sucrose pellets, with one lever designated as the reward
      lever. There were no group differences in response acquisition or lever
      discrimination on a fixed-ratio 1 (FR-1) schedule. During extinction sessions,
      CPEE offspring maintained higher levels of responding on the previously
      reinforced lever, suggesting that CPEE increases perseveration and/or impairs
      response inhibition but does not affect operant responding for an appetitive
      reinforcer or the ability to discriminate rewarding from nonrewarding stimuli. In
      contrast, there was no effect of CPEE on performance in the water maze in the
      maternal ethanol regimen used in this study. CPEE did not alter electrically
      evoked glutamate or GABA release from hippocampal brain slices. However, when
      slices were tested after delivery of a tetanizing stimulation (five 5-s trains at
      100 Hz), post-tetanic potentiation of electrically stimulated GABA release was
      greater in hippocampal slices obtained from CPEE offspring, whereas post-tetanic
      potentiation of electrically stimulated glutamate release was unaffected. These
      data suggest that conditioned learning is a sensitive behavioral measure of CPEE
      induced brain injury. Increased activity-dependent potentiation of GABA release
      in the hippocampus may contribute to alterations in synaptic plasticity observed
      in CPEE offspring.

PMID- 14600251
TI  - Green tea polyphenol epigallocatechin-3-gallate (EGCG) differentially inhibits
      interleukin-1 beta-induced expression of matrix metalloproteinase-1 and -13 in
      human chondrocytes.
AB  - Interleukin-1beta (IL-1beta)-induced inflammatory response in arthritic joints
      include the enhanced expression and activity of matrix metalloproteinases (MMPs),
      and their matrix degrading activity contribute to the irreversible loss of
      cartilage and may also be associated with sustained chronic inflammation. We have
      earlier shown that green tea (Camellia sinensis) polyphenol epigallocatechin-3
      gallate (EGCG) was non-toxic to human chondrocytes [Singh R, Ahmed S, Islam N,
      Goldberg VM, and Haqqi TM (2002) Arthritis Rheum 46: 2079-2086] and inhibits the
      expression of inflammatory mediators in arthritic joints [Haqqi TM, Anthony DD,
      Gupta S, Ahmed N, Lee MS, Kumar GK, and Mukhtar H (1999) Proc Natl Acad Sci USA
      96: 4524-4529]. Here we show that EGCG at micromolar concentrations was highly
      effective in inhibiting the IL-1beta-induced glycosaminoglycan (GAG) release from
      human cartilage explants in vitro. EGCG also inhibited the IL-1beta-induced mRNA
      and protein expression of MMP-1 and MMP-13 in human chondrocytes. Importantly,
      EGCG showed a differential, dose-dependent inhibitory effect on the expression
      and activity of MMP-13 and MMP-1. A similar differential dose-dependent
      inhibition of transcription factors NF-kappaB and AP-1 by EGCG was also noted.
      These results for the first time demonstrate a differential dose-dependent effect
      of EGCG on the expression and activity of MMPs and on the activities of
      transcription factors NF-kappaB and AP-1 and provide insights into the molecular
      basis of the reported anti-inflammatory effects of EGCG. These results also
      suggest that EGCG or compounds derived from it may be therapeutically effective
      inhibitors of IL-1beta-induced production of matrix-degrading enzymes in
      arthritis.

PMID- 14600254
TI  - Money back guarantee I: the problem. By Caveman.

PMID- 14600253
TI  - Mechanisms of cefadroxil uptake in the choroid plexus: studies in wild-type and
      PEPT2 knockout mice.
AB  - The choroid plexus uptake of [(3)H]cefadroxil was studied in peptide transporter
      2 (PEPT2) wild-type and null mice as a function of temperature, transport
      inhibitors, pH, and saturability. At normal pH (7.4) and temperature (37 degrees
      C), the uptake of 1 microM cefadroxil was reduced by 83% in PEPT2(-/-) mice as
      compared with PEPT2(+/+) mice (p < 0.001). A further reduction was achieved in
      null animals by reducing the temperature to 4 degrees C, or by adding saturating
      concentrations of unlabeled cefadroxil or p-aminohippurate (p < 0.05).
      Glycylsarcosine coadministration could inhibit the uptake of cefadroxil in
      PEPT2(+/+) mice (p < 0.01) but not PEPT2(-/-) mice. Although a proton-stimulated
      uptake of cefadroxil was demonstrated in PEPT2(+/+) mice (pH 6.5 versus pH 7.4; p
      < 0.01), no pH dependence was observed in PEPT2(-/-) mice. Kinetic parameters for
      cefadroxil (without p-aminohippurate) in wild-type mice were: V(max) = 5.4
      pmol/mg/min, K(m) = 34 microM, and K(d) = 0.0069 microl/mg/min; in the presence
      of p-aminohippurate, the parameters were: V(max) = 4.1 pmol/mg/min, K(m) = 27
      microM, and K(d) = 0.0064 microl/mg/min. In null animals, the kinetic parameters
      of cefadroxil (without p-aminohippurate) were: V(max) = 2.7 pmol/mg/min, K(m) =
      110 microM, and K(d) = 0.0084 microl/mg/min; in the presence of p-aminohippurate,
      only a K(d) = 0.010 microl/mg/min was observed. Based on kinetic and inhibitor
      analyses, it was determined that (under linear conditions), 80 to 85% of
      cefadroxil's uptake in choroid plexus is mediated by PEPT2, 10 to 15% by organic
      anion transporter(s), and 5% by nonspecific mechanisms. These findings
      demonstrate that PEPT2 is the primary transporter responsible for cefadroxil
      uptake in the choroid plexus. Moreover, the data suggest a role for PEPT2 in the
      clearance of peptidomimetics from cerebrospinal fluid.

PMID- 14600255
TI  - The small RNA world.

PMID- 14600256
TI  - T-cell integrins: more than just sticking points.
AB  - T cells use integrins in essentially all of their functions. They use integrins
      to migrate in and out of lymph nodes and, following infection, to migrate into
      other tissues. At the beginning of an immune response, integrins also participate
      in the immunological synapse formed between T cells and antigen-presenting cells.
      Because the ligands for integrins are widely expressed, integrin activity on T
      cells must be tightly controlled. Integrins become active following signalling
      through other membrane receptors, which cause both affinity alteration and an
      increase in integrin clustering. Lipid raft localization may increase integrin
      activity. Signalling pathways involving ADAP, Vav-1 and SKAP-55, as well as Rap1
      and RAPL, cause clustering of leukocyte function-associated antigen-1 (LFA-1;
      integrin alphaLbeta2). T-cell integrins can also signal, and the pathways
      dedicated to the migratory activity of T cells have been the most investigated so
      far. Active LFA-1 causes T-cell attachment and lamellipodial movement induced by
      myosin light chain kinase at the leading edge, whereas RhoA and ROCK cause T-cell
      detachment at the trailing edge. Another important signalling pathway acts
      through CasL/Crk, which might regulate the activity of the GTPases Rac and Rap1
      that have important roles in T-cell migration.

PMID- 14600257
TI  - Caveosomes and endocytosis of lipid rafts.
AB  - Endocytosis of various endogenous plasma membrane molecules, including signalling
      receptors, glycosphingolipids and glycosylphosphatidylinositol (GPI)-linked
      proteins, occurs in the absence of functional clathrin-coated pits. Most of these
      molecules are found in biochemically defined lipid rafts, which suggests that at
      least some clathrin-independent endocytosis may be raft specific or raft
      mediated. However, recent studies of the uptake of raft markers have revealed a
      diversity of internalization methods. Although lipid rafts may somehow be
      recognized by endocytic machinery, at this stage the data do not readily fit with
      the idea of a single raft-specific or raft-dependent endocytic pathway. Many
      studies report uptake of raft molecules by caveolar endocytosis (defined by
      sensitivity to cholesterol depletion and to overexpression of a specific mutant
      of dynamin 2). It is now apparent that this is a highly regulated process, and
      caveolin 1, one of the characteristic protein components of caveolae, might in
      fact act to slow or inhibit endocytosis. The molecular details of caveolar
      endocytosis have yet to be elucidated. Several sources indicate that clathrin
      independent uptake to a distinct class of caveolin-1-containing endosome, termed
      the caveosome, allows different types of endocytic mechanisms to have different
      functional consequences for the cell. It is likely that there are mechanisms that
      allow recruitment and targeting of specific molecules to caveosomes.

PMID- 14600258
TI  - RNAi analysis reveals an unexpected role for topoisomerase II in chromosome arm
      congression to a metaphase plate.
AB  - DNA topoisomerase II (Topo II) is a major component of mitotic chromosomes and an
      important drug target in cancer chemotherapy, however, its role in chromosome
      structure and dynamics remains controversial. We have used RNAi to deplete Topo
      II in Drosophila S2 cells in order to carry out a detailed functional analysis of
      the role of the protein during mitosis. We find that Topo II is not required for
      the assembly of a functional kinetochore or the targeting of chromosomal
      passenger proteins, nonetheless, it is essential for anaphase sister chromatid
      separation. In response to a long-running controversy, we show that Topo II does
      have some role in mitotic chromatin condensation. Chromosomes formed in its
      absence have a 2.5-fold decrease in the level of chromatin compaction, and are
      morphologically abnormal. However, it is clear that the overall programme of
      mitotic chromosome condensation can proceed without Topo II. Surprisingly, in
      metaphase cells depleted of Topo II, one or more chromosome arms frequently
      stretch out from the metaphase plate to the vicinity of the spindle pole. This is
      not kinetochore-based movement, as the centromere of the affected chromosome is
      located on the plate. This observation raises the possibility that further
      unexpected functions for Topo II may remain to be discovered.

PMID- 14600259
TI  - Preferentially localized dynein and perinuclear dynactin associate with nuclear
      pore complex proteins to mediate genomic union during mammalian fertilization.
AB  - Fertilization is complete once the parental genomes unite, and requires the
      migration of the egg nucleus to the sperm nucleus (female and male pronuclei,
      respectively) on microtubules within the inseminated egg. Neither the molecular
      mechanism of pronucleus binding to microtubules nor the role of motor proteins in
      regulating pronuclear motility has been fully characterized, and the failure of
      zygotic development in some patients suggests that they contribute to human
      infertility. Based on the minus-end direction of female pronuclear migration, we
      propose a role for cytoplasmic dynein and dynactin in associating with the
      pronuclear envelope and mediating genomic union. Our results show that dynein
      intermediate and heavy chains preferentially concentrate around the female
      pronucleus, whereas dynactin subunits p150Glued, p50 and p62 localize to the
      surfaces of both pronuclei. Transfection of antibodies against dynein and
      dynactin block female pronuclear migration in zygotes. Both parthenogenetic
      activation in oocytes and microtubule depolymerization in zygotes significantly
      reduce the localization of dynein to the female pronucleus but do not inhibit the
      pronuclear association of dynactin. When immunoprecipitated from zygotes,
      p150Glued associates with nuclear pore complex proteins, as well as the
      intermediate filament vimentin and dynein. Antibodies against nucleoporins and
      vimentin inhibit pronuclear apposition when transfected into zygotes. We conclude
      that preferentially localized dynein and perinuclear dynactin associate with the
      nuclear pore complex and vimentin and are required to mediate genomic union.
      These data suggest a model in which dynein accumulates and binds to the female
      pronucleus on sperm aster microtubules, where it interacts with dynactin,
      nucleoporins and vimentin.

PMID- 14600260
TI  - A caveolin-3 mutant that causes limb girdle muscular dystrophy type 1C disrupts
      Src localization and activity and induces apoptosis in skeletal myotubes.
AB  - Caveolins are membrane proteins that are the major coat proteins of caveolae,
      specialized lipid rafts in the plasma membrane that serve as scaffolding sites
      for many signaling complexes. Among the many signaling molecules associated with
      caveolins are the Src tyrosine kinases, whose activation regulates numerous
      cellular functions including the balance between cell survival and cell death.
      Several mutations in the muscle-specific caveolin, caveolin-3, lead to a form of
      autosomal dominant muscular dystrophy referred to as limb girdle muscular
      dystrophy type 1C (LGMD-1C). One of these mutations (here termed the 'TFT
      mutation') results in a deletion of a tripeptide (DeltaTFT(63-65)) that affects
      the scaffolding and oligomerization domains of caveolin-3. This mutation causes a
      90-95% loss of caveolin-3 protein levels and reduced formation of caveolae in
      skeletal muscle fibers. However, the effects of this mutation on the specific
      biochemical processes and cellular functions associated with caveolae have not
      been elucidated. We demonstrate that the TFT caveolin-3 mutation in post-mitotic
      skeletal myotubes causes severely reduced localization of caveolin-3 to the
      plasma membrane and to lipid rafts, and significantly inhibits caveolar function.
      The TFT mutation reduced the binding of Src to caveolin-3, diminished targeting
      of Src to lipid rafts, and caused abnormal perinuclear accumulation of Src. Along
      with these alterations of Src localization and targeting, there was elevated Src
      activation in myotubes expressing the TFT mutation and an increased incidence of
      apoptosis in those cells compared with control myotubes. The results of this
      study demonstrate that caveolin-3 mutations associated with LGMD-1C disrupt
      normal cellular signal transduction pathways associated with caveolae and cause
      apoptosis in muscle cells, all of which may reflect pathogenetic pathways that
      lead to muscle degeneration in these disorders.

PMID- 14600261
TI  - Specific sorting of the a1 isoform of the V-H+ATPase a subunit to nerve terminals
      where it associates with both synaptic vesicles and the presynaptic plasma
      membrane.
AB  - Vacuolar H+ATPase (V-ATPase) accumulates protons inside various intracellular
      organelles, generating the electrochemical proton gradient required for many
      vital cellular processes. V-ATPase is a complex enzyme with many subunits that
      are organized into two domains. The membrane domain that translocates protons
      contains a proteolipid oligomer of several c subunits and a 100 kDa a subunit.
      Several a-subunit isoforms have been described that are important for tissue
      specificity and targeting to different membrane compartments, and could also
      result in the generation of V-ATPases with different functional properties. In
      the present report, we have cloned the Torpedo marmorata a1 isoform. This isoform
      was found to be addressed specifically to nerve endings, whereas VATPases in the
      neuron cell bodies contain a different a-subunit isoform. In nerve terminals, the
      V-ATPase membrane domain is present not only in synaptic vesicles but also in the
      presynaptic plasma membrane, where its density could reach 200 molecules microm(
      2). This V-ATPase interacts with VAMP-2 and with the SNARE complexes involved in
      synaptic vesicle docking and exocytosis.

PMID- 14600262
TI  - Condensin-dependent localisation of topoisomerase II to an axial chromosomal
      structure is required for sister chromatid resolution during mitosis.
AB  - Assembly of compact mitotic chromosomes and resolution of sister chromatids are
      two essential processes for the correct segregation of the genome during mitosis.
      Condensin, a five-subunit protein complex, is thought to be required for
      chromosome condensation. However, recent genetic analysis suggests that condensin
      is only essential to resolve sister chromatids. To study further the function of
      condensin we have depleted DmSMC4, a subunit of the complex, from Drosophila S2
      cells by dsRNA-mediated interference. Cells lacking DmSMC4 assemble short mitotic
      chromosomes with unresolved sister chromatids where Barren, a non-SMC subunit of
      the complex is unable to localise. Topoisomerase II, however, binds mitotic
      chromatin after depletion of DmSMC4 but it is no longer confined to a central
      axial structure and becomes diffusely distributed all over the chromatin.
      Furthermore, cell extracts from DmSMC4 dsRNA-treated cells show significantly
      reduced topoisomerase II-dependent DNA decatenation activity in vitro.
      Nevertheless, DmSMC4-depleted chromosomes have centromeres and kinetochores that
      are able to segregate, although sister chromatid arms form extensive chromatin
      bridges during anaphase. These chromatin bridges do not result from inappropriate
      maintenance of sister chromatid cohesion by DRAD21, a subunit of the cohesin
      complex. Moreover, depletion of DmSMC4 prevents premature sister chromatid
      separation, caused by removal of DRAD21, allowing cells to exit mitosis with
      chromatin bridges. Our results suggest that condensin is required so that an
      axial chromatid structure can be organised where topoisomerase II can effectively
      promote sister chromatid resolution.

PMID- 14600263
TI  - Uncoordinated regulation of stress fibers and focal adhesions by DAP kinase.
AB  - Death-associated protein kinase (DAP kinase) is a proapoptotic,
      calcium/calmodulin-dependent serine/threonine kinase. Here, we report that DAP
      kinase phosphorylates the regulatory light chain of myosin II (MLC) both in vitro
      and in vivo, and that this phosphorylation occurs preferentially at residue
      Ser19. In quiescent fibroblasts, DAP kinase stabilizes stress fibers through
      phosphorylation of MLC, but it is dispensable for the formation of peripheral
      microfilament bundles. This cytoskeletal effect of DAP kinase occurs before the
      onset of apoptosis and does not require an intact death domain. In addition, DAP
      kinase is required for serum-induced stress-fiber formation, which is associated
      with the upregulation of its catalytic activity. Despite being both sufficient
      and necessary for the assembly or maintenance of stress fibers, DAP kinase is
      incapable of stimulating the formation of focal adhesions in quiescent cells.
      Moreover, it promotes the disassembly of focal adhesions but not stress fibers in
      cells receiving serum factors. Together, our results identify a novel and unique
      function of DAP kinase in the uncoupling of stress fibers and focal adhesions.
      Such uncoupling would lead to a perturbation of the balance between contractile
      and adhesion forces and subsequent cell detachment, which might contribute to its
      pro-apoptotic activity.

PMID- 14600264
TI  - Ran modulates spindle assembly by regulating a subset of TPX2 and Kid activities
      including Aurora A activation.
AB  - Ran, a GTPase in the Ras superfamily, is proposed to be a spatial regulator of
      microtubule spindle assembly by maintaining key spindle assembly factors in an
      active state close to chromatin. RanGTP is hypothesized to maintain the spindle
      assembly factors in the active state by binding to importin beta, part of the
      nuclear transport receptor complex, thereby preventing the inhibitory binding of
      the nuclear transport receptors to spindle assembly factors. To directly test
      this hypothesis, two putative downstream targets of the Ran spindle assembly
      pathway, TPX2, a protein required for correct spindle assembly and Kid, a
      chromokinesin involved in chromosome arm orientation on the spindle, were
      analyzed to determine if their direct binding to nuclear transport receptors
      inhibited their function. In the amino-terminal domain of TPX2 we identified
      nuclear targeting information, microtubule-binding and Aurora A binding
      activities. Nuclear transport receptor binding to TPX2 inhibited Aurora A binding
      activity but not the microtubule-binding activity of TPX2. Inhibition of the
      interaction between TPX2 and Aurora A prevented Aurora A activation and
      recruitment to microtubules. In addition we identified nuclear targeting
      information in both the amino-terminal microtubule-binding domain and the carboxy
      terminal DNA binding domain of Kid. However, the binding of nuclear transport
      receptors to Kid only inhibited the microtubule-binding activity of Kid.
      Therefore, by regulating a subset of TPX2 and Kid activities, Ran modulates at
      least two processes involved in spindle assembly.

PMID- 14600265
TI  - Visualization of Rab5 activity in living cells by FRET microscopy and influence
      of plasma-membrane-targeted Rab5 on clathrin-dependent endocytosis.
AB  - Rab5 is a small GTPase that controls endocytosis and early endosome dynamics. To
      visualize active, GTP-loaded Rab5 in living cells, we developed molecular sensors
      consisting of the Rab5-binding fragments of Rabaptin5 or EEA.1 fused to yellow
      fluorescent protein (YFP). Interaction of these sensors with GTP-bound Rab5 fused
      to cyan fluorescent protein (CFP) resulted in fluorescence resonance energy
      transfer (FRET) between CFP and YFP. Activated Rab5 was detected by FRET
      microscopy in endosomal compartments and often concentrated in microdomains in
      the endosomal membrane. Although the plasma membrane-localized activity of Rab5
      was not detected by light microscopy, overexpression of a GDP-bound mutant of CFP
      Rab5(S34N) inhibited internalization of the epidermal growth factor receptor by
      retaining receptors in clathrin-coated pits. To test whether the Rab5(S34N)
      mutant affects endocytosis directly at the plasma membrane, CFP-Rab5 was fused to
      the plasma membrane targeting sequence of K-Ras containing a CAAX motif. The
      resulting chimeric CFP-Rab5-CAAX was located mainly in the plasma membrane and
      was capable of binding GTP as judged by FRET microscopy with the Rabaptin5-based
      sensor. Interestingly, EEA.1 sensor did not follow activated Rab5-CAAX to the
      plasma membrane, suggesting that the interaction of EEA.1 with Rab5 plays a
      secondary role in EEA.1 targeting. Overexpression of CFP-Rab5(S34N)CAAX prevented
      endocytosis of receptors by retaining them in coated pits. These data suggest
      that the dominant-negative effect of the Rab5(S34N) mutant on the late stages of
      endocytosis can be mediated through the inhibition of cytosol-associated or
      plasma-membrane-associated rather than endosome-associated regulators of Rab
      proteins.

PMID- 14600266
TI  - A targeted deletion of the C-terminal end of titin, including the titin kinase
      domain, impairs myofibrillogenesis.
AB  - Titin is the largest protein known, and is essential for organising muscle
      sarcomeres. It has many domains with a variety of functions, and stretches from
      the Z-line to the M-line in the muscle sarcomere. Close to the M-line, titin
      contains a kinase domain, which is known to phosphorylate the Z-line protein
      telethonin in developing muscle (Mayans, O., van der Ven, P. F., Wilm, M., Mues,
      A., Young, P., Furst, D. O., Wilmanns, M. and Gautel, M. (1998) Nature 395, 863
      869). This phosphorylation is thought to be important for initiating or
      regulating myofibrillogenesis. We used a gene-targeting approach in cultured
      myoblasts to truncate the titin gene so that the kinase domain and other domains
      downstream of the kinase were not expressed. We recovered cells in which one
      allele was targeted. We found that these cells expressed both the full-length and
      a truncated titin that was approximately 0.2 MDa smaller than the corresponding
      band from wild-type cells. Myofibrillogenesis in these cells was impaired, in
      that the myotubes were shorter, and the organisation of the muscle sarcomeres, M-
      and Z-lines was poorer than in wild-type cells. There was also an overall
      reduction in levels of titin and skeletal myosin expression. These results
      suggest that the activity of the titin kinase domain and downstream sequence are
      important in organising myofibrils both at the M- and the Z-line early in
      myofibrillogenesis.

PMID- 14600267
TI  - The trans-membrane protein p25 forms highly specialized domains that regulate
      membrane composition and dynamics.
AB  - Trans-membrane proteins of the p24 family are abundant, oligomeric proteins
      predominantly found in cis-Golgi membranes. They are not easily studied in vivo
      and their functions are controversial. We found that p25 can be targeted to the
      plasma membrane after inactivation of its canonical KKXX motif (KK to SS, p25SS),
      and that p25SS causes the co-transport of other p24 proteins beyond the Golgi
      complex, indicating that wild-type p25 plays a crucial role in retaining p24
      proteins in cis-Golgi membranes. We then made use of these observations to study
      the intrinsic properties of these proteins, when present in a different membrane
      context. At the cell surface, the p25SS mutant segregates away from both the
      transferrin receptor and markers of lipid rafts, which are enriched in
      cholesterol and glycosphingolipids. This suggests that p25SS localizes to, or
      contributes to form, specialized membrane domains, presumably corresponding to
      oligomers of p25SS and other p24 proteins. Once at the cell surface, p25SS is
      endocytosed, together with other p24 proteins, and eventually accumulates in late
      endosomes, where it remains confined to well-defined membrane regions visible by
      electron microscopy. We find that this p25SS accumulation causes a concomitant
      accumulation of cholesterol in late endosomes, and an inhibition of their
      motility - two processes that are functionally linked. Yet, the p25SS-rich
      regions themselves seem to exclude not only Lamp1 but also accumulated
      cholesterol. One may envision that p25SS accumulation, by excluding cholesterol
      from oligomers, eventually overloads neighboring late endosomal membranes with
      cholesterol beyond their capacity (see Discussion). In any case, our data show
      that p25 and presumably other p24 proteins are endowed with the intrinsic
      capacity to form highly specialized domains that control membrane composition and
      dynamics. We propose that p25 and other p24 proteins control the fidelity of
      membrane transport by maintaining cholesterol-poor membranes in the Golgi
      complex.

PMID- 14600268
TI  - Residues within the myristoylation motif determine intracellular targeting of the
      neuronal Ca2+ sensor protein KChIP1 to post-ER transport vesicles and traffic of
      Kv4 K+ channels.
AB  - KChIPs (K+ channel interacting proteins) regulate the function of A-type Kv4
      potassium channels by modifying channel properties and by increasing their cell
      surface expression. We have explored factors affecting the localisation of Kv4.2
      and the targeting of KChIP1 and other NCS proteins by using GFP-variant fusion
      proteins expressed in HeLa cells. ECFP-Kv4.2 expressed alone was not retained in
      the ER but reached the Golgi complex. In cells co-expressing ECFP-Kv4.2 and
      KChIP1-EYFP, the two proteins were co-localised and were mainly present on the
      plasma membrane. When KChIP1-EYFP was expressed alone it was instead targeted to
      punctate structures. This was distinct from the localisation of the NCS proteins
      NCS-1 and hippocalcin, which were targeted to the trans-Golgi network (TGN) and
      plasma membrane. The membrane localisation of each NCS protein required
      myristoylation and minimal myristoylation motifs of hippocalcin or KChIP1 were
      sufficient to target fusion proteins to either TGN/plasma membrane or to punctate
      structures. The existence of targeting information within the N-terminal motifs
      was confirmed by mutagenesis of residues corresponding to three conserved basic
      amino acids in hippocalcin and NCS-1 at positions 3, 7 and 9. Residues at these
      positions determined intracellular targeting to the different organelles.
      Myristoylation and correct targeting of KChIP1 was required for the efficient
      traffic of ECFP-Kv4.2 to the plasma membrane. Expression of KChIP1(1-11)-EYFP
      resulted in the formation of enlarged structures that were positive for ERGIC-53
      and beta-COP. ECFP-Kv4.2 was also accumulated in these structures suggesting that
      KChIP1(1-11)-EYFP inhibited traffic out of the ERGIC. We suggest that KChIP1 is
      targeted by its myristoylation motif to post-ER transport vesicles where it could
      interact with and regulate the traffic of Kv4 channels to the plasma membrane
      under the influence of localised Ca2+ signals.

PMID- 14600269
TI  - Beta-dystrobrevin interacts directly with kinesin heavy chain in brain.
AB  - Beta-dystrobrevin, a member of the dystrobrevin protein family, is a dystrophin
      related and -associated protein restricted to non-muscle tissues and is highly
      expressed in kidney, liver and brain. Dystrobrevins are now thought to play an
      important role in intracellular signal transduction, in addition to providing a
      membrane scaffold in muscle, but the precise role of beta-dystrobrevin has not
      yet been determined. To study beta-dystrobrevin's function in brain, we used the
      yeast two-hybrid approach to look for interacting proteins. Four overlapping
      clones were identified that encoded Kif5A, a neuronal member of the Kif5 family
      of proteins that consists of the heavy chains of conventional kinesin. A direct
      interaction of beta-dystrobrevin with Kif5A was confirmed by in vitro and in vivo
      association assays. Co-immunoprecipitation with a monoclonal kinesin heavy chain
      antibody precipitated both alpha- and beta-dystrobrevin, indicating that this
      interaction is not restricted to the beta-dystrobrevin isoform. The site for
      Kif5A binding to beta-dystrobrevin was localized in a carboxyl-terminal region
      that seems to be important in heavy chain-mediated kinesin interactions and is
      highly homologous in all three Kif5 isoforms, Kif5A, Kif5B and Kif5C. Pull-down
      and immunofluorescence experiments also showed a direct interaction between beta
      dystrobrevin and Kif5B. Our findings suggest a novel function for dystrobrevin as
      a motor protein receptor that might play a major role in the transport of
      components of the dystrophin-associated protein complex to specific sites in the
      cell.

PMID- 14600271
TI  - Pulmonary responses of mice, rats, and hamsters to subchronic inhalation of
      ultrafine titanium dioxide particles.
AB  - A multispecies, subchronic, inhalation study comparing pulmonary responses to
      ultrafine titanium dioxide (uf-TiO(2)) was performed. Female rats, mice, and
      hamsters were exposed to aerosol concentrations of 0.5, 2.0, or 10 mg/m(3) uf
      TiO(2) particles for 6 h/day, 5 days/week, for 13 weeks. Following the exposure
      period, animals were held for recovery periods of 4, 13, 26, or 52 weeks (49
      weeks for the uf-TiO(2)-exposed hamsters) and, at each time point, uf-TiO(2)
      burdens in the lung and lymph nodes and selected lung responses were examined.
      The responses studied were chosen to assess a variety of pulmonary parameters,
      including inflammation, cytotoxicity, lung cell proliferation, and
      histopathological alterations. Retained lung burdens increased in a dose
      dependent manner in all three species and were at a maximum at the end of
      exposures. Mice and rats had similar retained lung burdens at the end of the
      exposures when expressed as mg uf-TiO(2)/mg dry lung, whereas hamsters had
      retained lung burdens that were significantly lower. Lung burdens in all three
      species decreased with time after exposure, and, at the end of the recovery
      period, the percentage of the lung particle burden remaining in the 10 mg/m(3)
      group was 57, 45, and 3% for rat, mouse, and hamster, respectively. The
      retardation of particle clearance from the lungs in mice and rats of the 10
      mg/m(3) group indicated that pulmonary particle overload had been achieved in
      these animals. Pulmonary inflammation in rats and mice exposed to 10 mg/m(3) was
      evidenced by increased numbers of macrophages and neutrophils and increased
      concentrations of soluble markers in bronchoalveolar lavage fluid (BALF). The
      initial neutrophil response in rats was greater than in mice, whereas the
      relative increase of macrophages was less than in mice. The neutrophilic response
      of rats, but not mice, declined in a time-dependent manner correlating with
      declining lung burdens; however, the fraction of recovered neutrophils at 52
      weeks postexposure was equivalent in the two species. Consistent increases in
      soluble indicators of toxicity in the BALF (LDH and protein) occurred principally
      in rats and mice exposed to 10 mg/m(3) and diminished with time postexposure.
      There were no significant changes in cellular response or with markers indicating
      toxicity in hamsters, reflecting the capacity of these animals to rapidly clear
      particles from the lung. Progressive epithelial and fibroproliferative changes
      were observed in rats of the 10 mg/m(3) group. These lesions consisted of foci of
      alveolar epithelial proliferation of metaplastic epithelial cells (so-called
      alveolar bronchiolization) circumscribing aggregated foci of heavily particle
      laden macrophages. The observed epithelial proliferative changes were also
      manifested in rats as an increase in alveolar epithelial cell labeling in cell
      proliferation studies. Associated with these foci of epithelial proliferation
      were interstitial particle accumulation and alveolar septal fibrosis. These
      lesions became more pronounced with increasing time postexposure. Epithelial,
      metaplastic, and fibroproliferative changes were not noted in either mice or
      hamsters. In summary, there were significant species differences in the pulmonary
      responses to inhaled uf-TiO(2) particles. Under conditions where the lung uf
      TiO(2) burdens were equivalent, rats developed a more severe inflammatory
      response than mice and, subsequently, developed progressive epithelial and
      fibroproliferative changes. Clearance of particles from the lung was markedly
      impaired in mice and rats exposed to 10 mg/m(3) uf-TiO(2), whereas clearance in
      hamsters did not appear to be affected at any of the administered doses. These
      data are consistent with the results of a companion study using inhaled
      pigmentary (fine mode) TiO(2) (Bermudez et al., 2002) and demonstrate that the
      pulmonary responses of rats exposed to ultrafine particulate concentrations
      likely to induce pulmonary overload are different from similarly exposed mice and
      hamsters. These differences can be explained both by pulmonary respy response and
      by particle dosimetry differences among these rodent species.

PMID- 14600270
TI  - Biglycan and decorin induce morphological and cytoskeletal changes involving
      signalling by the small GTPases RhoA and Rac1 resulting in lung fibroblast
      migration.
AB  - Biglycan and decorin are small chondroitin/dermatan sulphate proteoglycans in the
      extracellular matrix of connective tissue that belong to the family of
      structurally related proteoglycans called small leucine-rich repeat proteins. We
      show for the first time that biglycan and decorin induce morphological and
      cytoskeletal changes in fibroblasts, resulting in an increase in migration.
      Biglycan changed the cell shape of fibroblasts with formation of long protruding
      filamentous processes. This was also seen for decorin but to a lesser extent.
      Using fluorescence staining of F-actin fibres it was possible to show that these
      long filamentous processes were supported by long thick bundles of actin,
      together with an induced formation of stress fibres after stimulation with
      biglycan and decorin. Moreover, a reorganisation of alpha-smooth muscle actin was
      clearly seen in these cultures. Decorin also stimulated alpha-smooth muscle actin
      expression in the cells. Using cDNA Atlas Arrays we were also able to show that
      the mRNA level of a number of the intracellular regulators and effectors involved
      in cell migration were increased. For example, the focal adhesion proteins
      paxillin and zyxin, and some of the small Rho GTPases such as RhoA, Rac1 and
      Cdc42 were upregulated. After treatment with biglycan or decorin, additional
      results showed an increased activation of RhoA (1.8- and 1.5-fold, respectively)
      and Rac1 (1.8- and 1.5-fold, respectively) after 15 minutes. These factors are
      known to be involved in fibroblast migration, and as expected a 1.3- to 1.6-fold
      increase in migration could be observed after stimulation with biglycan or
      decorin. This induced migration was caused by the core protein, as treatment with
      glycosaminoglycan chains alone did not have any effect. In summary, these data
      indicate that biglycan- and decorin-induced fibroblast cytoskeletal and
      signalling changes result in an increased cell migration, and demonstrate their
      potential role in the remodelling process.

PMID- 14600272
TI  - Characteristic expression profiles induced by genotoxic carcinogens in rat liver.
AB  - When applied in toxicological studies, the recently developed gene expression
      profiling techniques using microarrays, which brought forth the new field of
      toxicogenomics, facilitate the interpretation of a toxic compound's mechanism of
      action. In this study, we investigated whether genotoxic carcinogens at doses
      known to induce liver tumors in the 2-year rat bioassay deregulate a common set
      of genes in a short-term in vivo study and, if so, whether these deregulated
      genes represent defined biological pathways. Rats were dosed with the four
      genotoxic hepatocarcinogens dimethylnitrosamine (4 mg/kg/day), 2-nitrofluorene
      (44 mg/kg/day), aflatoxin B1 (0.24 mg/kg/day), and 4-(methylnitrosamino)-1-(3
      pyridyl)-1-butanone (NNK, 20 mg/kg/day). After treatment for up to 14 days, the
      expression profiles of the livers were analyzed on Affymetrix RG_U34A
      microarrays. Among the significantly upregulated genes were a set of target genes
      of the tumor suppressor protein p53, indicating a DNA damage response. Such a
      response was expected and, therefore, confirmed the validity of our approach. In
      addition, the gene expression changes suggest a specific detoxification response,
      the activation of proliferative and survival signaling pathways, and some cell
      structural changes. These responses were strong throughout the 14 day time course
      for 2-nitrofluorene and aflatoxin B1; in the case of dimethylnitrosamine and NNK,
      the effects were weakly detectable at day 1 and then increased with time. For
      dimethylnitrosamine and aflatoxin B1, which caused observable inflammation in
      vivo, we found a corresponding upregulation of inflammatory genes at the same
      time points. Thus, by the toxicogenomic analysis of short-term in vivo studies,
      we identified genes and pathways commonly deregulated by genotoxic carcinogens,
      which may be indicative for the early events in tumorigenesis and, thus,
      predictive of later tumor development.

PMID- 14600273
TI  - Cadmium-induced mitochondrial membrane-potential dissipation does not necessarily
      require cytosolic oxidative stress: studies using rhodamine-123 fluorescence
      unquenching.
AB  - The impact of cadmium on the cellular redox state and mitochondrial membrane
      potential (psi(m)) has been studied by monitoring dichlorofluorescein (DCF),
      CMXRos (dichlorodihydrofluorescein diacetate, chloromethyl-X-rosamine), and Rh
      123 fluorescence in 5-day-old TC7 cells, a highly differentiated clone of the
      human intestinal Caco-2 cell line. Flow cytometry analyses, using DCFH oxidation
      to DCF, clearly revealed that a 30-min incubation to 50 microM cadmium (Cd) is
      sufficient to induce reactive oxygen species (ROS) formation; this effect was
      completely eliminated by the presence of 50 mM mannitol for the 30-min incubation
      period, but mannitol only partially scavenged ROS for the longer period of time
      studied. Imaging studies using fluorescence video microscopy revealed a parallel
      increase in (DCF) fluorescence in the nuclear and cytoplasmic regions as soon as
      Cd was added to the exposure medium. Flow cytometry analyses monitoring CMXRos
      fluorescence clearly showed that Cd also leads to psi(m) disruption, but,
      contrary to what was observed for ROS formation, mannitol was completely
      inefficient in preventing this effect. Further investigation using fluorescence
      microscopy and Rh-123 fluorescence unquenching revealed that although mannitol
      did not protect against Cd-induced dissipation of psi(m), it considerably delayed
      the process. We found that Rh-123 unquenching, occurring during probe
      redistribution, is a suitable tool to monitor the decrease of psi(m). We conclude
      that Cd rapidly induces ROS formation, mainly hydroxyl radical species OH(*), as
      well as the loss of psi(m). However, psi(m) dissipation does not necessarily
      require cellular OH(*) and may occur in the absence of apparent oxidative injury.

PMID- 14600274
TI  - Neurochemical effects of repeated gestational exposure to chlorpyrifos in
      developing rats.
AB  - The neurochemical effects in developing rats exposed during gestation to the
      anticholinesterase organophosphorus insecticide chlorpyrifos (CPS) were
      determined. Pregnant rats were dosed daily with CPS (0, 3, or 7 mg/kg) in corn
      oil from gestation days (GD) 6-20. Pups were euthanized on postnatal days (PND)
      1, 3, 6, 9, 12, and 30 for the determination of brain cholinesterase (ChE) and
      choline acetyltransferase (ChAT) activities, along with muscarinic receptor
      (mAChR) densities, the levels of the high-affinity choline uptake (HACU) system,
      and the vesicular acetylcholine transporter (VAChT). ChE activities were
      inhibited about 15 and 30% on PND 1, in the low- and high-dosage groups,
      respectively, and were not different from control values by PND 6. mAChR
      densities on PND 1 were reduced in the high-dosage group by about 18, 21, and
      17%, using 3H-N-methylscopolamine, 3H-quinuclidinyl benzilate, and 3H-4-DAMP,
      respectively, as ligands, and were not different from control levels by PND 6.
      ChAT activity was decreased by approximately 12% in the high-dosage group on PND
      9, 12, and 30. HACU levels, using 3H-hemicholinium-3 as the ligand, were reduced
      by approximately 25% on PND 6 in the low- and high-dosage groups, and by
      approximately 14 and 21% on PND 12 and 30, only in the high-dosage group. Levels
      of the VAChT were reduced by a range of 13-31% on PND 3 through 30 in the high
      dosage group, using 3H-AH5183 (vesamicol) as the ligand. These data suggest that
      gestational exposure to 7 mg/kg/day CPS results in long-term alterations of
      presynaptic cholinergic neurochemistry.

PMID- 14600275
TI  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) alters the regulation of Pax5 in
      lipopolysaccharide-activated B cells.
AB  - The environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) produces
      a profound suppression of the primary immunoglobulin-M (IgM) antibody response.
      The suppression of IgM production by TCDD can occur through direct interactions
      with the B cell, is aryl hydrocarbon receptor-dependent, and is mediated through
      alterations in the differentiation of B cells into plasma cells. The objective of
      the present investigation was to characterize the effects of TCDD on the
      regulation of Pax5, a crucial repressor of B-cell differentiation, and four
      downstream targets that are directly regulated by Pax5 and involved in
      immunoglobulin regulation, immunoglobulin heavy chain (IgH), kappa light chain
      (Igkappa), J chain, and X box protein-1 (XBP-1). Lipopolysaccharide (LPS)
      activation of aryl hydrocarbon receptor-expressing CH12.LX cells induced B cell
      differentiation and robust immunoglobulin secretion that was markedly (~50%)
      suppressed in the presence of 10 nM TCDD. Kinetic studies show that LPS
      activation induced a time-dependent decrease in Pax5 mRNA levels, protein, and
      DNA binding activity during a 72-h culture period that was almost completely
      blocked in the presence of TCDD. Concomitant with the time-dependent down
      regulation of Pax5 in LPS-activated control CH12.LX cells, a reciprocal induction
      of IgH, Igkappa, J chain mRNA levels, and cellular XBP-1 was observed.
      Conversely, and consistent with the absence of Pax5 down-regulation associated
      with TCDD treatment, IgH, Igkappa, J chain mRNA, and XBP-1 protein were
      persistently repressed in LPS-activated CH12.LX cells. Collectively, these
      studies demonstrate the involvement of altered Pax5 regulation in the suppression
      of the primary IgM antibody response by TCDD.

PMID- 14600276
TI  - Estimation of the upper limit of human butyrylcholinesterase dose required for
      protection against organophosphates toxicity: a mathematically based
      toxicokinetic model.
AB  - Human butyrylcholinesterase (HuBChE) is a drug candidate for protection against
      organophosphates (OP) intoxication. A mathematically based model was validated
      and employed to better understand the role of the endogenous HuBChE in
      detoxification of OPs and to estimate the dose of exogenous HuBChE required for
      enhancing protection of humans from lethal exposure to OPs. The model addresses
      the relationship between the HuBChE dose needed to maintain a certain residual
      activity of human acetylcholinesterase (HuAChE) and the following parameters: (1)
      level and duration of exposure, (2) bimolecular rate constants of inhibition of
      HuAChE (kA) and HuBChE (kB) by OPs, and (3) time elapsed from enzyme load. The
      equation derived for the calculation of HuBChE dose requires the knowledge of
      kA/kB in human blood and the rate constant of HuBChE elimination. Predictions of
      HuBChE doses were validated by in vitro experiments and data of published human
      studies. These predictions highlight two parameters that are likely to decrease
      the calculated dose: (1) the rapid consumption of the less toxic isomers of OPs
      in human plasma, and (2) the volume of distribution of HuBChE that appears
      significantly greater than the volume of plasma. The first part of the analysis
      of the proposed model was focused on acute bolus exposures and suggests that
      upper limit doses of 134, 115, and 249 mg/70 kg are sufficient to protect RBC
      AChE above 30% of baseline activity following a challenge with 1 LD(50) VX,
      soman, and sarin, respectively. The principles of the validated model should be
      applicable for advanced predictions of HuBChE dose for protection against
      continuous exposures to OPs.

PMID- 14600277
TI  - Modes of cell death in rat liver after monocrotaline exposure.
AB  - Monocrotaline (MCT) is a pyrrolizidine alkaloid (PA) plant toxin that produces
      sinusoidal endothelial cell (SEC) injury, hemorrhage, fibrin deposition, and
      coagulative hepatic parenchymal cell (HPC) oncosis in centrilobular regions of
      rat livers. Cells with apoptotic morphology have been observed in the livers of
      animals exposed to other PAs. Whether apoptosis occurs in the livers of MCT
      treated animals and whether it is required for full manifestation of pathological
      changes is not known. To determine this, rats were treated with 300 mg MCT/kg,
      and apoptosis was detected by transmission electron microscopy and the TUNEL (TdT
      mediated dUTP nick end labeling) assay. MCT produced significant apoptosis in the
      liver by 4 h after treatment. To determine if MCT kills cultured HPCs by
      apoptosis, HPCs were isolated from the livers of rats and exposed to MCT. MCT
      caused a concentration-dependent release of alanine aminotransferase (ALT), a
      marker of HPC injury. Furthermore, caspase 3 was activated and TUNEL staining
      increased in MCT-treated HPCs. MCT-induced TUNEL staining and release of ALT into
      the medium were completely prevented by the pancaspase inhibitors z-VAD.fmk and
      IDN-7314, suggesting that MCT kills cultured HPCs by apoptosis. To determine if
      caspase inhibition prevents MCT-induced apoptosis in the liver, rats were
      cotreated with MCT and IDN-7314. IDN-7314 reduced MCT-induced TUNEL staining in
      the liver and release of ALT into the plasma. Morphometric analysis confirmed
      that IDN-7314 reduced HPC oncosis in the liver by approximately 50%. Inasmuch as
      HPC hypoxia occurred in the livers of MCT-treated animals, upregulation of the
      hypoxia-regulated cell-death factor, BNIP3 (Bcl2/adenovirus EIB 19kD-interacting
      protein 3), was examined. BNIP3 was increased in the livers of mice treated 24 h
      earlier with MCT. Results from these studies show that MCT kills cultured HPCs by
      apoptosis but causes both oncosis and apoptosis in the liver in vivo.
      Furthermore, caspase inhibition reduces both apoptosis and HPC oncosis in the
      liver after MCT exposure.

PMID- 14600278
TI  - Human interindividual variation in lymphocyte UDP-glucuronosyltransferases as a
      determinant of in vitro benzo[a]pyrene covalent binding and cytotoxicity.
AB  - UDP-glucuronosyltransterases (UGTs) catalyse the glucuronidation and elimination
      of most xenobiotics and, thereby, may prevent their alternative bioactivation to
      carcinogenic and teratogenic reactive intermediates. Previous studies have shown
      that glucuronidation, bioactivation, and covalent binding of the
      carcinogen/teratogen benzo[a]pyrene (BP) in rat lymphocytes accurately reflected
      those processes in hepatic microsomes from the same animals. Accordingly,
      lymphocytes from 12 normal human volunteers were incubated with BP metabolites to
      determine UGT variability and its potential toxicological relevance. Over 200
      fold interindividual variability was observed in both the glucuronidation and
      covalent binding of BP metabolites, with decreasing total glucuronidation among
      subjects correlating with a decreased UGT-modulated reduction in covalent binding
      (R(2) = 0.8272, p < 0.01) and, in six subjects, enhanced cytotoxicity (r = 
      0.9338, p < 0.001). Decreased glucuronidation of both BP diols (r = -0.9106, p <
      0.001) and BP diones (r = -0.9625, p < 0.005), but not BP monophenols, correlated
      with enhanced cytotoxicity. These results provide the first evidence for
      substantial interindividual variability in UGT activities for BP metabolites
      among the normal population and suggest that UGT-deficient individuals may be at
      increased risk from the reactive intermediate-mediated effects of BP and related
      xenobiotics.

PMID- 14600279
TI  - Dermal, oral, and inhalation pharmacokinetics of methyl tertiary butyl ether
      (MTBE) in human volunteers.
AB  - Methyl tertiary butyl ether (MTBE), a gasoline additive used to increase octane
      and reduce carbon monoxide emissions and ozone precursors, has contaminated
      drinking water and can lead to exposure by oral, inhalation, and dermal routes.
      To determine its dermal, oral, and inhalation kinetics, 14 volunteers were
      exposed to 51.3 microg/ml MTBE dermally in tap water for 1 h, drank 2.8 mg MTBE
      in 250 ml Gatorade(R), and inhaled 3.1 ppm. MTBE for 1 h. Blood and exhaled
      breath samples were then obtained. Blood MTBE peaked between 15 and 30 min
      following oral exposure, at the end of inhalation exposure, and ~5 min after
      dermal exposure. Elimination by each route was described well by a three
      compartment model (Rsq >0.9). The Akaike Information Criterion for the three
      compartment model was smaller than the two-compartment model, supporting it over
      the two-compartment model. One metabolite, tertiary butyl alcohol (TBA), measured
      in blood slowly increased and plateaued, but it did not return to the pre
      exposure baseline at the 24-h follow-up. TBA is very water-soluble and has a
      blood:air partition ratio of 462, reducing elimination by exhalation. Oral
      exposure resulted in a significantly greater MTBE metabolism into TBA than by
      other routes based on a greater blood TBA:MTBE AUC ratio, implying significant
      first-pass metabolism. The slower TBA elimination may make it a better biomarker
      of MTBE exposure, though one must consider the exposure route when estimating
      MTBE exposure from TBA because of first-pass metabolism. Most subjects had a
      baseline blood TBA of 1-3 ppb. Because TBA is found in consumer products and can
      be used as a fuel additive, it is not a definitive marker of MTBE exposure. These
      data provide the risk assessment process of pharmacokinetic information relevant
      to the media through which most exposures occur-air and drinking water.

PMID- 14600280
TI  - Statistical analysis of nonmonotonic dose-response relationships: research design
      and analysis of nasal cell proliferation in rats exposed to formaldehyde.
AB  - Statistical analyses of nonmonotonic dose-response curves are proposed,
      experimental designs to detect low-dose effects of J-shaped curves are suggested,
      and sample sizes are provided. For quantal data such as cancer incidence rates,
      much larger numbers of animals are required than for continuous data such as
      biomarker measurements. For example, 155 animals per dose group are required to
      have at least an 80% chance of detecting a decrease from a 20% incidence in
      controls to an incidence of 10% at a low dose. For a continuous measurement, only
      14 animals per group are required to have at least an 80% chance of detecting a
      change of the mean by one standard deviation of the control group. Experimental
      designs based on three dose groups plus controls are discussed to detect
      nonmonotonicity or to estimate the zero equivalent dose (ZED), i.e., the dose
      that produces a response equal to the average response in the controls. Cell
      proliferation data in the nasal respiratory epithelium of rats exposed to
      formaldehyde by inhalation are used to illustrate the statistical procedures.
      Statistically significant departures from a monotonic dose response were obtained
      for time-weighted average labeling indices with an estimated ZED at a
      formaldehyde dose of 5.4 ppm, with a lower 95% confidence limit of 2.7 ppm. It is
      concluded that demonstration of a statistically significant bi-phasic dose
      response curve, together with estimation of the resulting ZED, could serve as a
      point-of departure in establishing a reference dose for low-dose risk assessment.

PMID- 14600281
TI  - Nonmonotonic dose-response relationships: mechanistic basis, kinetic modeling,
      and implications for risk assessment.
AB  - Dose-response curves for the first interaction of a chemical with a biochemical
      target molecule are usually monotonic; i.e., they increase or decrease over the
      entire dose range. However, for reactions of a complex biological system to a
      toxicant, nonmonotonic (biphasic) dose-effect relationships can be observed,
      showing a decrease at low dose followed by an increase at high dose, or vice
      versa. We present four examples to demonstrate that nonmonotonic dose-response
      relationships can result from superimposition of monotonic dose responses of
      component biological reactions. Examples include (i) a membrane-receptor model
      with receptor subtypes of different ligand affinity and opposing downstream
      effects (adenosine receptors A1 vs. A2), (ii) androgen receptor-mediated gene
      expression driven by homodimers, but not mixed-ligand dimers, (iii) repair of
      background DNA damage by enzymatic activity induced by adducts formed by a
      xenobiotic, (iv) rate of mutation as a consequence of DNA damage times rate of
      cell division, the latter being modulated by cell-cycle delay at low-level DNA
      damage, and cell-cycle acceleration due to regenerative hyperplasia at cytotoxic
      dose levels. Quantitative analyses based on biological models are shown, and
      factors that affect the degree of nonmonotonicity are identified. It is noted
      that threshold-type dose-response curves could in fact be nonmonotonic. Our
      analysis should promote a scientific discussion of biphasic dose responses and
      the concept termed "hormesis," and of default procedures for low-dose
      extrapolation in toxicological risk assessment.

PMID- 14600282
TI  - The mycotoxin fumonisin B1 alters the proliferation and the barrier function of
      porcine intestinal epithelial cells.
AB  - Fumonisin B1 (FB1) is a mycotoxin produced by Fusarium verticillioides (formerly
      F. moniliforme), a fungus that commonly contaminates maize. FB1 causes
      toxicological effects in laboratory and domestic animals including pigs. Because
      the gastrointestinal tract represents the first barrier met by exogenous food
      compounds, the purpose of this study was to investigate the effects of FB1 on
      IPEC-1, a porcine intestinal epithelial cell line. We first verified that low
      concentrations of FB1 did not exert any cytotoxic effect on IPEC-1. Indeed,
      significant LDH release was only observed for FB1 concentrations greater than 50
      and 700 microM on proliferating and nonproliferating cells, respectively. We then
      demonstrated that FB1 inhibits proliferation of IPEC-1. Fluorescence-activated
      cell sorting (FACS) analysis of the cell cycle indicated that FB1 blocks the
      proliferation of intestinal cells in the G0/G1 phase. Similar results were
      obtained with LLC-PK1, a renal porcine epithelial cell line, which is considered
      to be a good model for studying FB1 in vitro effects. We have also assessed the
      effects of FB1 on the integrity of the barrier formed by the intestinal
      epithelium. We demonstrated that FB1 decreases the transepithelial electrical
      resistance (TEER) of IPEC-1 in a time- and dose-dependent manner. This effect was
      only noticed after a long exposure (8-12 days of treatment). FB1 induced the TEER
      decrease independently of the cell differentiation stage, and this effect was
      partially reversible. Taken together, our data indicate that FB1 alters the
      proliferation and the barrier function of intestinal cells. These results may
      have implications for humans and animals consuming FB1-contaminated food or feed.

PMID- 14600283
TI  - Lung deposition and clearance of inhaled vanadium pentoxide in chronically
      exposed F344 rats and B6C3F1 mice.
AB  - Female F344 rats and B6C3F1 mice were exposed to vanadium pentoxide (V2O5) at
      concentrations of 0, 0.5, 1, or 2 mg/m3 (rats) and 0, 1, 2, or 4 mg/m3 (mice) for
      6 h/day, 5 days/week (for up to 18 months), by whole-body inhalation. Lung
      weights and lung burdens of vanadium were determined for exposed animals after 1,
      5, and 12 days and after 1, 2, 6, 12, and 18 months of V2O5 exposure. Blood
      vanadium concentrations were determined at 1, 2, 6, 12, and 18 months for all
      animals including controls. A model that assumed a first-order deposition rate
      and a first-order elimination rate for vanadium was employed to fit the lung
      burden data. Comparisons between exposed groups indicated a progressive increase
      in lung weight with exposure concentration and time on exposure for both species.
      The vanadium lung burdens appeared to reach steady state in the lowest exposure
      groups (0.5 and 1 mg/m3 for rats and mice, respectively) but showed a decline in
      the higher exposure groups. This deposition pattern was similar between rats and
      mice but the maximum lung burdens were observed at different times (1 or 2 months
      in mice vs. 6 months in rats). The vanadium deposition rate decreased faster in
      mice, while the elimination half-lives of vanadium lung burdens were about six-
      to nine-fold shorter in mice than in rats at 1 and 2 mg/m3. Thus, the retention
      of vanadium in the lungs at 18 months was lower in mice (approximately 2%
      retained) compared with rats (13-15% retained) at the common exposure
      concentrations of 1 and 2 mg/m3. The lung burden data were approximately
      proportional to the exposure concentration in both species, likely due to
      concomitant decreases in deposition and elimination to a similar extent with
      increasing exposure. The area under the lung burden versus time curves and the
      area under the blood concentration (control-normalized) versus time curves were
      also proportional to exposure concentration. The progression of pathological
      changes in the lung with exposure and time is thought to affect the pattern
      and/or extent of vanadium deposition in the lungs following repeated exposures to
      V2O5.

PMID- 14600284
TI  - Non-coplanar 2,2',3,5',6-pentachlorobiphenyl (PCB 95) amplifies ionotropic
      glutamate receptor signaling in embryonic cerebellar granule neurons by a
      mechanism involving ryanodine receptors.
AB  - The mechanisms by which non-coplanar 2,2',3,5',6-pentachlorobiphenyl (PCB 95) and
      rapamycin interact with ryanodine receptor (RyR) complexes to alter Ca2+
      signaling, were explored in intact cerebellar granule neurons. PCB 95 (10 microM,
      20 min) significantly increased the number of neurons responding to caffeine. PCB
      95 sensitization of RyR-mediated responses was further supported by the
      observations that ryanodine pretreatment blocked response to caffeine and
      coplanar 2,4,4',5-tetrachlorobiphenyl (PCB 66), which lacks RyR activity, failed
      to sensitize neurons. PCB 95 did not significantly alter levels of resting
      cytosolic Ca2+ nor thapsigargin-sensitive Ca2+ stores, suggesting a more complex
      mechanism than sensitization from increased cytosolic Ca2+ or an increased
      endoplasmic reticulum/cytosolic Ca2+ gradient. The immunosuppressant, rapamycin,
      sensitized neurons to caffeine in a manner similar to PCB 95, suggesting a common
      mechanism. PCB 95 or rapamycin significantly enhanced Ca2+ responses following N
      methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl4-isoxasolepropiate
      (AMPA) receptor activation. Store depletion or direct block of RyR with ryanodine
      enhanced responses to NMDA. PCB 95 further enhanced these responses to NMDA.
      These results suggest that PCB 95 and rapamycin enhance NMDA- and AMPA-mediated
      Ca2+ signals by modifying a functional association of the FKBP12/RyR complex that
      results in amplification of glutamate signaling in cultured cerebellar granule
      neurons in culture.

PMID- 14600285
TI  - The effect of chlorpyrifos and chlorpyrifos-oxon on brain cholinesterase,
      muscarinic receptor binding, and neurotrophin levels in rats following early
      postnatal exposure.
AB  - Chlorpyrifos (CPS) is a widely used diethyl organophosphorus insecticide in
      agricultural settings. Household and urinary residue analysis has suggested that
      children in agricultural communities are at risk of exposure to diethyl
      organophosphorus insecticides. The effects of repeated postnatal exposure to CPS
      and its metabolite chlorpyrifos-oxon (CPO) on total muscarinic acetylcholine
      receptor (mAChR) binding, nerve growth factor (NGF) levels, and brain derived
      neurotrophic factor (BDNF) levels in the forebrain of neonatal rats were
      investigated. Peak inhibition of brain cholinesterase (ChE) for CPS and CPO was
      determined after acute exposure to dosages of each compound (a low and a high for
      each), which produced similar degrees of initial ChE inhibition. Pups were
      administered CPS (1.5 or 3.0 mg/kg), CPO (0.25 or 0.35 mg/kg), or the corn oil
      vehicle by daily gavage from postnatal day 1 (PND 1) through PND 6. This exposure
      paradigm resulted in persistent ChE inhibition by CPS but only transient
      inhibition by CPO, suggesting that, even though the initial ChE inhibition is
      similar between compounds, the effects of repeated exposure differ significantly.
      Forebrain mAChR density, as measured by the binding of 3H-QNB, and NGF levels
      were significantly reduced on PND 4 and 7 after CPS but not on PND 12. No effects
      on mAChR density or NGF levels were observed with CPO. No effects on BDNF levels
      were observed with either compound. The data suggest that the persistent ChE
      inhibition and decreased mAChR binding may play a role in the decreased NGF
      levels following CPS exposure.

PMID- 14600286
TI  - Assessing gene expression in lung subcompartments utilizing in situ RNA
      preservation.
AB  - The mechanisms of toxicant-mediated lung injury and repair are influenced by the
      considerable spatial heterogeneity that exists within the conducting airways of
      the lungs. As a result of this heterogeneity, significant differences and
      similarities in gene expression are observed throughout lung subcompartments. RNA
      based technologies such as real-time reverse transcription polymerase chain
      reaction (real-time RT-PCR) and cDNA microarray analysis of gene expression
      provide valuable clues to understanding the mechanisms of toxicant-induced
      injury. Isolating RNA from lung subcompartments has previously involved
      considerable time and labor-intensive processes that limit the number of animals
      that could be processed in a day. The aim of this study was to determine if
      intact, high-quality RNA could be preserved in situ over a period of time to
      delay the need to immediately perform site-specific lung subcompartment
      microdissections and RNA isolations. Two hours after 1-nitronaphthalene
      treatment, rat lungs were inflated with and stored in RNA preservation solution
      and stored at 4 degrees C for 7 days. RNA was isolated from the lung
      subcompartments isolated by microdissection. After 7 days of storage, the RNA was
      intact, of high quality, and could be used for real-time RT-PCR to examine
      heterogeneous gene expression in the lung subcompartments. In summary, this
      simplified technique of in situ RNA preservation and site-specific lung
      subcompartment microdissection allows the isolation of intact, high-quality RNA
      that may be used with molecular RNA-based technologies that will significantly
      accelerate our understanding of pulmonary injury and repair mechanisms.

PMID- 14600287
TI  - Epigallocatechin gallate modulates CYP450 isoforms in the female Swiss-Webster
      mouse.
AB  - This study was designed to determine the effect of the in vivo administration of
      epigallocatechin gallate (EGCG) and epicatechin gallate (ECG) on enzymes involved
      in the synthesis and metabolism of estradiol. EGCG (12.5, 25, or 50 mg/kg/day,
      i.p.) or ECG (12.5 or 25 mg/kg/day, i.p.) was administered to female Swiss
      Webster mice for 7 days. The chemicals were well tolerated by the mice with the
      exception of EGCG given at 50 mg/kg, which resulted in severe hepatic necrosis
      and a 67% mortality rate. Following the administration of nontoxic doses of EGCG
      and ECG, aromatase (CYP19), CYP3A, CYP1A, and catechol O-methyltransferase (COMT)
      were measured. Additionally, the activity of CYP2E1 was determined, since this
      CYP450 isoform is important in the bioactivation of numerous carcinogens. The
      results demonstrated that ovarian aromatase activity was inhibited 56% by EGCG
      (25 and 12.5 mg/kg), but not ECG, while hepatic CYP3A catalytic activity and
      polypeptide levels were increased 31 +/- 4 and 47 +/- 2%, respectively, by 25
      mg/kg of EGCG. However, ECG (but not EGCG) inhibited CYP1A catalytic activity and
      polypeptide levels (31 +/- 5 and 47 +/- 5%, respectively). Hepatic and renal
      COMT, as well as renal CYP3A remained unchanged following catechin dosing.
      Hepatic CYP2E1 catalytic activity and polypeptide levels were significantly
      increased (37 +/- 3 and 22 +/- 3%) following administration of EGCG (25 mg/kg).
      These results indicate that EGCG modulates enzymes responsible for both the
      synthesis and metabolism of estradiol, which may provide a potential mechanism
      for the reported action of EGCG, reported action as an inhibitor of breast tumor
      growth.

PMID- 14600288
TI  - QT and RR intervals in conscious and anesthetized guinea pigs with highly varying
      RR intervals and given QTc-lengthening test articles.
AB  - A facile system for obtaining electrocardiograms from conscious animals was used
      to conduct studies on 12 animals studied both conscious and anesthetized, on 4
      conscious animals given vehicle (0.5% methylcellulose) and QT-lengthening test
      articles, and on 6 animals given test articles thought to not lengthen QTc. In 12
      animals whose ECGs were monitored via a bipolar transthoracic ECG, heart rates
      were slowed with 1.0 mg/kg zatebradine, while they were conscious in their
      slings, and after being anesthetized with ketamine/xylazine. The following
      regression equations were obtained relating QT to RR: QT = 44.7 ln RR - 132.9, r2
      = 0.7, for conscious animals; QT = 79.4 ln RR - 287.4, r2 = 0.8 for anesthetized
      animals, with RR intervals varying between 150 and 550 ms. The anesthetic
      increases QT at all RR intervals (p < 0.001), but does not change the slope of
      the relationship between QT and RR when compared with the conscious guinea pig.
      The Fridericia method was best for correcting QT for RR interval in conscious
      guinea pigs, but the Bazett method was best for correcting in anesthetized
      animals. QTc lengthened significantly in all conscious guinea pigs given, orally,
      cisapride, ketoconazole, and sotalol (positive test articles) and did not change
      with methylcellulose (the vehicle) or with propranolol, verapamil, or enalapril
      (negative controls). These techniques and relationships demonstrate that this
      methodology may be useful in exploring torsadogenic effects of novel
      pharmacological entities.

PMID- 14600289
TI  - Hexachlorobenzene-induced early changes in ornithine decarboxylase and protein
      tyrosine kinase activities, polyamines and c-Myc, c-Fos and c-Jun proto-oncogenes
      in rat liver.
AB  - Hexachlorobenzene (HCB) is a lipophilic chemical compound that is widely
      distributed in the environment. HCB is known to cause liver tumors in
      experimental animals. In the present study the in vivo effect of HCB treatment on
      ornithine decarboxylase (ODC) and protein tyrosine kinase (PTK) activities, free
      polyamine content, and c-Myc, c-Fos, and c-Jun protein levels in rat liver were
      investigated. HCB (1000 mg/kg body weight) increased hepatic immunodetectable c
      Myc, c-Fos, and c-Jun levels after 6 h, and ODC activity and spermine and
      putrescine content after 18 and 24 h, while maximum stimulation of PTK activity
      occurred at 12 h. PTK and ODC activities varied in a dose-dependent manner. The
      time-course of c-Myc, c-Fos, and c-Jun protein levels was different for each
      proto-oncogene. They were all elevated at the second day of treatment, while only
      c-Fos and c-Jun remained elevated after 10 days of HCB exposure. These data
      jointly suggest that the increase in ODC activity may be the consequence of proto
      oncogene induction. The alterations in PTK activity suggest that the growth
      factor signal transduction pathway may be involved in the regulation of the proto
      oncogene levels or/and ODC activity. The decrease in PTK activity after the first
      day, even in the presence of alpha-D-Difluoromethylornithine (DFMO), an inhibitor
      of ODC activity, suggests that it is not regulated by polyamines. These results
      may be relevant to the early molecular events involved in HCB tumor promoter
      activity in rat liver.

PMID- 14600290
TI  - Motor impairment in rats exposed to PCBs and methylmercury during early
      development.
AB  - Epidemiological and laboratory studies indicate that polychlorinated biphenyls
      (PCBs) and methyl mercury (MeHg) may have additive or interactive adverse effects
      on nervous system function. Prior studies have shown that high doses of MeHg
      target the cerebellum and impair balance and coordination, but the effects of
      PCBs on cerebellar function were unknown. In addition, the combined effects of
      PCBs and MeHg on cerebellar function have not been studied previously. Therefore,
      we investigated the effects of developmental exposure to PCBs, MeHg, or PCBs +
      MeHg on three motor tasks that involve cerebellar functions. Female Long-Evans
      rats were exposed to MeHg (0.5 ppm in drinking water), PCBs (6-mg/kg/d Aroclor
      1254), PCBs + MeHg, or vehicle only beginning 4 weeks prior to breeding, through
      pregnancy, and continuing through postnatal day (PND) 16. Starting at
      approximately PND 60, one male and one female from each litter were tested on
      three motor tasks that involve cerebellar function. PCB + MeHg-exposed rats were
      impaired relative to the controls on a task requiring them to traverse a rotating
      rod. Rats exposed to PCBs alone were also somewhat impaired relative to the
      controls, whereas MeHg-exposed rats were not significantly different from the
      controls. There were no statistically significant deficits related to PCB or MeHg
      exposure on a vertical rope-climbing test or a parallel bar test. Our results
      demonstrate that the possibility of additive neurotoxic effects of PCBs and MeHg
      needs to be seriously considered.

PMID- 14600291
TI  - Neurodevelopmental defects in zebrafish (Danio rerio) at environmentally relevant
      dioxin (TCDD) concentrations.
AB  - Persistent ecotoxicants, such as dioxin and PCBs, are thought to pose one of the
      greatest threats to public and ecological health in the industrial world. These
      compounds cause a range of macroscopic malformations, particularly to the
      craniofacial apparatus and cardiovascular system during vertebrate development.
      However, little is known about microscopic effects, especially on the sensitive
      early life stages or on the molecular basis of developmental neurotoxicity. Using
      zebrafish (Danio rerio), we have explored neurological deficits caused by early
      life exposure to environmentally relevant concentrations of dioxin. We show,
      using a quantitative stereological technique, that 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD) substantially reduces the capacity for embryonic brain development,
      causing a 30% reduction in total neuronal number in the 168-h larval brain. Using
      transgenic GFP-expressing zebrafish lines, we link this to decreased expression
      of key developmentally regulated genes, namely neurogenin and sonic hedgehog.
      This disruption of neuronal development provides the basis for understanding the
      neurotoxic effects of these compounds.

PMID- 14600292
TI  - Huntingtin: alive and well and working in middle management.
AB  - A decade after the discovery of the HD gene, huntingtin is implicated in signal
      transduction in neuronal and nonneuronal cells. Its predicted physical
      properties, dynamic subcellular locations, and variable protein associations
      suggest that huntingtin may act to organize components of signal transduction
      complexes. This middle management position befits a ubiquitous, conserved protein
      and provides the opportunity for some subtle piece of mischief that leads
      eventually to a devastating inherited human disorder.

PMID- 14600293
TI  - Signal transduction and genes-to-behaviors pathways in psychiatric diseases.
AB  - Although psychiatric diseases are among the most common and destructive of all
      human illnesses, the molecular and cellular mechanisms underlying their complex
      origins remain to be elucidated. Dysfunction of critical intracellular signaling
      pathways is very likely to be involved. This conclusion is based on a number of
      observations, including the short- and long-term cellular effects of psychiatric
      drugs; the critical role signaling pathways play in neurotransmitter,
      neuropeptide, and neurohormone communication; and the fact that signaling
      pathways are principle regulators of the diverse array of behavioral symptoms
      experienced by patients. The genomics era has brought to psychiatry an abundance
      of genetic linkage and candidate gene findings. The difficult task--now under way
      -is to discern the functional relevance of these results. Recent evidence
      suggests the involvement of the ubiquitous protein phosphatase 2B (calcineurin),
      a critical regulator of many signal transduction pathways, as a schizophrenia
      susceptibility gene. It is likely that genetic findings in severe psychiatric
      disorders will continue to implicate direct and indirect modulation of critical
      intracellular signaling pathways.

PMID- 14600294
TI  - Signaling pathways take aim at neurotransmitter transporters.
AB  - Neurotransmitter transporters are the target of various pharmacological agents
      used to treat psychological or cognitive conditions, such as depression and
      attention-deficit disorder. In addition, some of the effects of stimulant-type
      drugs of abuse result from inhibition of neurotransmitter transporters. Robinson
      describes the intersection between neurotransmitter transporters and signaling
      pathways. Neurotransmitter transporters can be regulated by altering the rate of
      internalization and insertion into the plasma membrane to control cell surface
      expression or by altering the activity of the transporters within the membrane.
      As the mechanisms governing regulation of these transporters become elucidated,
      new potential therapeutic targets may be revealed, given the many processes
      affected by the activity of neurotransmitter transporters.

PMID- 14600295
TI  - Evidence-based practices or value-based services?

PMID- 14600297
TI  - Datapoints: suicide prevention in schools: are we reaching minority youths?

PMID- 14600298
TI  - Psychopharmacology: underuse of evidence-based treatments in psychiatry.

PMID- 14600299
TI  - Drug policy by analogy: well, it's like this...

PMID- 14600300
TI  - Psychiatric rehabilitation in a community mental health center.

PMID- 14600301
TI  - Level-of-care decision making in behavioral health services: the LOCUS and the
      CALOCUS.

PMID- 14600302
TI  - Introduction to the special section on the President's New Freedom Commission
      report.

PMID- 14600303
TI  - The President's New Freedom Commission: recommendations to transform mental
      health care in America.

PMID- 14600304
TI  - The Campaign for Mental Health Reform: a new advocacy partnership.

PMID- 14600305
TI  - The Commission's report and its implications for psychiatry.

PMID- 14600306
TI  - A view from managed behavioral health.

PMID- 14600307
TI  - Integrating psychotherapy and pharmacotherapy to improve outcomes among patients
      with mood disorders.
AB  - A number of studies have demonstrated comparable benefits of psychosocial
      interventions and pharmacologic treatments in subgroups of patients with mood
      disorders. The two treatment modalities are often combined in clinical practice.
      However, concerns about the costs of health care are paramount. For the optimum
      but judicious use of resources, it is valuable for mental health professionals to
      know the indications for and evidence pertaining to the efficacy of combined
      treatment. The authors demonstrate that a reexamination of existing research data
      in light of the recent advances in understanding of the design of clinical trials
      reveals a systematic underestimation of the benefits of combined treatment for
      certain subgroups of patients. Existing studies of combined treatments need to be
      reexamined in light of information about design sensitivity, ceiling effects, and
      nonspecific placebo effects. The authors summarize by arguing for a new
      generation of adequately powered investigations of efficacy, which they believe
      is necessary before the issue of cost-effectiveness can be properly addressed.

PMID- 14600308
TI  - Integrating treatment with rehabilitation for persons with major mental
      illnesses.
AB  - Psychiatric treatment and rehabilitation are integrated, seamless approaches
      aimed at restoring persons with major mental disorders to their best possible
      level of functioning and quality of life. Driven by a thorough assessment,
      treatment and rehabilitation are keyed to the stage and type of each individual's
      disorder. Examples of coordinated treatment and rehabilitation are
      pharmacotherapy, supported employment, social skills training, family
      psychoeducation, assertive community treatment, and integrated programs for
      persons with dual diagnoses. The authors conclude by proposing seven principles
      to guide mental health practitioners in their integration of pharmacologic and
      psychosocial interventions.

PMID- 14600309
TI  - Integrated treatment of schizophrenia.
AB  - The importance of combining psychosocial and pharmacologic interventions for
      optimum outcome in the treatment of schizophrenia is now well recognized.
      However, less research is available on ways in which the two types of treatment
      may affect each other. This article reviews research and principles applying to
      the integrated use of current psychosocial and pharmacologic treatments for
      schizophrenia. Emphasis is placed on areas of interaction, including patient
      adherence and the effect of antipsychotic medications on cognitive functioning.
      Recommendations are presented for specific clinical situations.

PMID- 14600310
TI  - Integration of behavioral and physical health care for a medicaid population
      through a public-public partnership.
AB  - This article documents a unique organizational, legal, and financial partnership
      between a state, a university, a Medicaid managed health care plan, and a county
      to provide integrated mental health, substance abuse, and primary and specialty
      health care services to Medicaid, low-income, and indigent consumers in Washtenaw
      county, Michigan. Major regulatory, financial, and clinical changes were required
      within and among the various partners in the Washtenaw County Integrated Health
      Care Project. A new entity--the Washtenaw Community Health Organization--was
      created to implement the project. By sharing resources as well as financial
      risks, the state, the county, and the university have been able to provide
      ongoing integrated care to a vulnerable population of patients. Although resource
      intensive in conceptualization and implementation, the project can be viewed as a
      model for other states that face growing needy populations and decreasing
      Medicaid budgets.

PMID- 14600311
TI  - Family caregivers' perceptions of barriers to and supports of participation in
      their children's out-of-home treatment.
AB  - OBJECTIVE: Although the importance of family caregivers' involvement in their
      children's mental health treatment is increasingly recognized, factors that
      influence caregivers' participation are not clearly understood. This study
      examined the views of family caregivers whose children received out-of-home
      treatment to determine the amount and types of family caregivers' participation
      in their children's treatment, the caregivers' perceptions of barriers and
      supports to participation, and the relationship of barriers and supports to
      caregivers' participation and satisfaction with care. METHODS: As part of a
      national survey, a subsample of 102 family caregivers from 31 states whose
      children were in a residential treatment center, psychiatric unit, or group home
      answered a questionnaire that included questions about their participation in
      their children's treatment and about barriers and supports to their
      participation. RESULTS: Family caregivers identified as barriers concrete factors
      such as cost of transportation and distance from service providers as well as
      more intangible factors such as lack of communication between staff members of
      different programs and negative attitudes of staff members. CONCLUSIONS: Programs
      seeking to create a more supportive environment for family caregivers'
      involvement in out-of-home care will need to seek out family members' perceptions
      of their experience with their children's treatment and their views about factors
      that would help increase their participation.

PMID- 14600313
TI  - Helping parents with serious mental illness retain custody of their children.

PMID- 14600312
TI  - Pervasive developmental disorders among children and adolescents attending
      psychiatric day treatment.
AB  - OBJECTIVE: This study sought to determine the prevalence of pervasive
      developmental disorders (PDD) among children admitted to a state hospital day
      treatment service and to characterize the psychiatric disturbance of patients
      with PDD. METHODS: A total of 146 consecutively admitted patients were evaluated
      for PDD. Patients who had PDD were compared with a sample of age- and sex-matched
      patients in day treatment who did not have PDD. Psychiatric symptoms, family
      history, and developmental and educational histories were examined. RESULTS: Of
      the 146 patients, 20 (14 percent) met criteria for PDD. An additional five
      patients who had PDD were included, yielding a final sample of 25. Only two of an
      array of psychiatric symptoms were more prevalent among patients with PDD:
      engaging in unusual fantasy and talking to themselves, animals, or inanimate
      objects. Significantly more patients with PDD had a history of speech delay,
      language abnormalities, and inexplicable or lengthy episodes of crying or
      screaming. The groups did not differ significantly in IQ or global functioning.
      Seven patients with PDD (28 percent) met criteria for childhood-onset
      schizophrenia, and 19 (76 percent) had symptoms of a tic disorder. CONCLUSIONS:
      The study found that PDD is not rare and that children with PDD represent a
      significant subgroup of children with serious emotional disturbance referred for
      psychiatric treatment. The findings support the view that PDD may be easily
      missed because it may be mild and associated with psychiatric disturbances that
      are present among other severely ill youngsters.

PMID- 14600314
TI  - A more compassionate model for treating children with severe mental disturbances.

PMID- 14600315
TI  - Silver and Bronze Achievement Awards.

PMID- 14600316
TI  - Patients' concerns about and perceptions of electronic psychiatric records.
AB  - This study assessed concerns about and perceptions of electronic psychiatric
      records in a university psychiatric adult outpatient clinic. Forty-one patients
      who refused to have their psychiatric records transferred to the electronic
      record system were compared with 39 patients who agreed to an electronic record.
      Regardless of whether or not they refused to have their information transferred
      to an electronic record, a majority of patients reported numerous concerns about
      electronic records, such as concerns about unauthorized access to their records
      by parties within the university health care system. Patients' concerns may
      affect patient disclosure and other help-seeking behavior and therefore must be
      addressed by clinicians and health care systems.

PMID- 14600318
TI  - Relationship of youth satisfaction with mental health services and changes in
      symptoms and functioning.
AB  - This study examined how youth-reported satisfaction with specialty mental health
      services was associated with youths' symptom and functioning change. Change in
      clinical functioning was assessed prospectively on the basis of parent, youth,
      and interviewer report for 369 youths (aged nine to 18 years at study entry)
      receiving mental health services. Satisfaction was assessed at two-year follow
      up. The results indicated that satisfaction was only minimally associated with
      clinical change, and only in the case of youth-reported clinical change. Parent-
      and interviewer-reported change were not associated with consumer satisfaction.
      These results suggest that consumer satisfaction is not a good indicator of
      effectiveness of treatment in changing clinical functioning.

PMID- 14600317
TI  - Rates of refusal to participate in research studies among men and women.
AB  - Studies have indicated that, among persons with serious mental illness, women may
      be less likely to participate in clinical research studies than men. This study
      examined refusal rates by gender in four recent studies that included persons
      with a range of diagnoses and that used various interventions and methods.
      Examination of the four studies indicated that women are no more likely than men
      to decline to participate in studies but that women may be underrepresented in
      target populations. When feasible, oversampling may be useful to increase the
      participation of women or of any other underrepresented demographic group in
      research studies.

PMID- 14600319
TI  - Dosages and outcomes.

PMID- 14600322
TI  - Assessing outcomes of prevention interventions.

PMID- 14600324
TI  - A pilot study evaluating a peer led and professional led physical activity
      intervention with blue-collar employees.
AB  - OBJECTIVE: To measure the effect of a physical activity intervention, based on
      social cognitive theory, delivered by a peer and a professional leader. DESIGN:
      Quasi-experimental. SETTING: Three locations at a large Mid-Western railroad.
      SUBJECTS: One hundred and forty-eight skilled labor employees participated: one
      hundred and twenty completed the study. MEASURES: Self-reported energy
      expenditure, self-efficacy and stages of change. RESULTS: ANOVA and categorical
      analysis using rates and proportions were used for evaluation. The peer group had
      a non-significant short-term increase in energy expenditure of 3%, which returned
      to baseline post intervention. The professional and control groups showed a non
      significant decrease in energy expenditure of 5% and 9%, respectively. The peer
      (p < 0.002) and professional groups (p < 0.004) showed significant increases in
      average stages scores. The peer group maintained increases over time (p < 0.001).
      The peer and professional led groups showed a 54% and 24% increase in the number
      of employees reporting regular physical activity over time, respectively. The
      peer group also showed positive trends in self-efficacy. CONCLUSIONS: The peer
      intervention enhanced self-efficacy and self-reported physical activity. A job
      layoff at the professional led site confounded comparisons between locations.
      Employees reported high energy expenditure and high BMI values, suggesting that a
      weight management intervention may be more appropriate and appealing in this
      population.

PMID- 14600325
TI  - Perception differences between groups of employees identifying the factors that
      influence a return to work after a work-related musculoskeletal injury.
AB  - Employee health and productivity losses as a result of work-related injury are
      estimated to be US dollars 1.2 trillion annually to US companies. This is
      approximately 14.3% of the gross domestic product [6,8,11,35]. Workers'
      compensation, medical care, and short and long-term disability are a part of
      these costs. Controlling or eliminating these costs is a problem for US employers
      [3,6,14,21,29]. The study discussed in this article examined the perceptions of
      manufacturing employees in identifying factors that influence a return to work
      after a work-related musculoskeletal injury. The classification of employees who
      participated in this study were safety professionals, supervisors and workers
      from the manufacturing industry in central Kentucky. The worker group consisted
      of material handlers, assembly line workers and quality control inspectors. The
      participants completed a developed survey instrument, the Return to Work
      Perception Survey. This survey instrument examined the perception of the
      participants on factors related to return to work: company policies and
      procedures, job satisfaction, worker relationships and work environment. The
      results indicated safety professionals and supervisors perceptions differ from
      workers on the variables of job satisfaction, worker relationships and work
      environment. Their perceptions did not differ on the variable relating to company
      policies and procedures. In addition, the safety professional and supervisor
      groups rated the items addressing job satisfaction higher than did the worker
      group. The worker group did not differ from one another on any of the factors.
      Implications of this study for manufacturing companies suggest (a). identifying
      those issues contributing to employee job satisfaction, (b). developing a plan
      for achieving increased job satisfaction and employee recognition at the
      workplace among all workers, and (c). consider allowing employees to develop new
      capacities and new learning, thus fostering motivation and job satisfaction
      [18,20].

PMID- 14600326
TI  - The needs and experiences of injured workers: a participatory research study.
AB  - This paper reports on the findings of a participatory research study in which 290
      injured workers in Ontario, Canada responded to a survey that was developed and
      administered by a group of university researchers in partnership with injured
      worker peer researchers. The objectives of the study were to gain a broad view of
      the needs and experiences of injured workers and to develop strategies for
      change. Findings indicated that many injured workers experience undue financial,
      emotional and physical hardship during the compensation, treatment and
      rehabilitation process. These hardships are experienced due to perceived lack of
      respect, insufficient information concerning rights and the return-to-work
      process, and limited opportunities for input into the medical or rehabilitation
      process. Recommendations for increasing the power of workers and creating a more
      supportive climate are included.

PMID- 14600327
TI  - Constructing the program impact theory for an evidence-based work rehabilitation
      program for workers with low back pain.
AB  - PURPOSE: Several low back pain work rehabilitation programs have been developed
      and evaluated for their outcomes. Unfortunately, the program impact theory for
      these programs is not described, and consequently, the exact mechanisms of action
      by which these programs intend to increase the probability of return to work
      remain unknown. This lack of knowledge jeopardizes the implementation of
      effective programs by health professionals and managers. The objective of this
      paper is to present the results of an exploratory study aimed at building the
      program impact theory for the PREVICAP work rehabilitation program. METHODS: The
      program impact theory was develop by conducting: unpublished documents and
      scientific literature analyses, individual and group discussions with multiple
      stakeholders and observation of program reality by reviewing the files of workers
      who completed the program. RESULTS: The PREVICAP program's impact theory was
      elaborated based on an ecological approach to work rehabilitation. Program goals
      and objectives were defined for the three dimensions of the model: the worker,
      the work environment and the interaction between the worker and his work
      environment. Two program action mechanisms were defined and describe how the
      program was intended to achieve its expected outcomes. CONCLUSIONS: This study
      made explicit the PREVICAP program impact theory and can help rehabilitation
      practitioners to address work disability according to an ecological model.

PMID- 14600328
TI  - Cost-effectiveness of a prework screening program for the University of Illinois
      at Chicago physical plant.
AB  - A post-offer screening program jointly developed by the Occupational and Physical
      Therapy Departments (University of Illinois at Chicago) was first implemented in
      March 1998. A total of 712 screens were completed from 3-01-98 through 2-28-01. A
      quasi-experimental design was utilized to analyze changes in Workers'
      Compensation costs between the three-year period prior to, and the three-year
      period following program inception. Additionally, injury rates and mean cost per
      injury were compared between injuries sustained between 3-98 and 3-01 which were
      incurred by workers who had passed screening and those that had not been
      screened. Finally, the tabulated cost per screen and reduction in Workers'
      Compensation costs allowed derivation of a dollar spent/ dollar saved ratio.
      Dramatic declines in number of injuries, total costs and mean cost per case
      occurred in the three-year period following program inception. Mean cost per case
      also dramatically declined comparing injured workers who had passed screening
      versus those who had never been screened. Cost savings were over US dollars 18
      per dollar spent on the program. While a number of mitigating variables may have
      accounted for some of the profound effects noted, decrease in average cost per
      case (indicating possible reduction in severity of injury) was consistent with
      existing literature.

PMID- 14600329
TI  - Role of workplace safety: a revisit of the relationship between job satisfaction
      and employment status.
AB  - This study evaluated the relationship between employment status (i.e., part- and
      full-time) and job satisfaction, with the focus on the moderating roles of
      perceived injury risk and injury incidence. The results found that the level of
      job satisfaction for full-time workers was about the same regardless of the level
      of injury risk they perceived. In contrast, job satisfaction of part-time workers
      was significantly higher when they perceived low injury risk rather than high
      injury risk. The findings also supported the potential adverse impact of injury
      incidence and injury risk on job satisfaction for both part- and full-time
      workers. This study highlighted the importance of understanding both workplace
      safety and job satisfaction when attempting to understand the differences between
      part-time and full-time workers.

PMID- 14600330
TI  - Future time orientation and employment of individuals with a spinal cord injury:
      does current work status reflect a greater orientation toward the future?
AB  - Differences in future time orientation were investigated among 317 individuals
      with spinal cord injuries according to work status. The results of an analysis of
      variance indicated a significant difference on future time orientation between
      individuals with an active community role (full-time or part-time employed,
      student, or volunteer) versus a non-active community role (unemployed or
      retired). In a post-hoc analysis of covariance (with depression as the
      covariate), these differences between work statuses on future time orientation
      were no longer significant, though a significant main effect by depression was
      observed. In both analyses, individuals with active community roles had higher
      future time orientation scores than individuals without active community roles.
      Suggestions for future research were briefly proposed.

PMID- 14600331
TI  - Comparison of a simulated versus work environment lifting task on L5/S1
      compression forces.
AB  - Since a patient's ability to perform simulated work activities guides return-to
      work decisions, a significant question to address is whether the simulated work
      environment accurately reflects the actual work environment. Work hardening
      programs have been used extensively as a method of rehabilitating workers to
      return to their pre-injury functioning levels. Re-training workers to lift boxes
      is a common method used to simulate the work environment. Although very few boxes
      used in the real work environment have handles, boxes with handles are often used
      in the simulated work environment. The difference in compression forces at the
      L5/S1 joint while lifting boxes with and without handles was investigated. The
      Lift Trak Motion Analysis system was used to estimate lumbar isometric
      compression forces exerted while lifting a 20-pound (9.07-kg) box. The results
      indicated that estimates of compression forces when lifting a box without handles
      were significantly different (p < 0.01) than when lifting the same box with
      handles. Based on these results, it is recommended that work hardening
      professionals carefully re-evaluate the simulated work environments currently
      being used for treatment.

PMID- 14600332
TI  - The costs of job accommodations for employees with low back pain.
AB  - Accommodations are interventions designed to reduce exposure to factors that
      limit the activities of an impaired individual. The process incurs costs due to
      job analysis, implementation and follow up. This theoretical paper expands a
      model of the ergonomic intervention process and provides data on costs of
      accommodating individuals with musculoskeletal disorders, particularly low back
      pain. Accommodations begin with evaluation and documentation of exposure to risk
      factors. The methods depend on the budget and clinical utility of the data. A
      full hazard analysis may require 1-hour managerial time plus 1-hour employee time
      per job. Studies by the Department of Labor and others indicate that at least a
      quarter of problem jobs could be addressed faster and for less than US dollars
      500. Follow-up incurs variable employee and managerial time; an ergonomist may be
      required in 15% of cases. The benefit is expected mainly from reducing
      compensation costs. Universal solutions could increase the benefits.

PMID- 14600333
TI  - CT-MRI automatic surface-based registration schemes combining global and local
      optimization techniques.
AB  - Medical image registration is commonly required in order to combine the
      complementary information provided by different medical imaging modalities. In
      this paper, a new automatic registration scheme is proposed to register 3-D CT-MR
      head images and is currently tested on a clinical environment. The proposed
      scheme, after the preprocessing and the outer surface extraction of the data, is
      based on the use the rigid transformation method, in conjunction with a
      combination of global and local optimization techniques. Analytically, the paper
      exploits the optimization efficiency of three widely used optimization
      techniques, in obtaining the parameters of the rigid transformation model: the
      Downhill Simplex Method, the Genetic Algorithms and the Simulated Annealing.
      These optimization techniques are further combined by the sequential application
      of the Powell optimization method in order to refine the registration and
      increase its accuracy. A comparative study involving these optimization
      techniques in conjunction with the rigid transformation, and two other methods,
      the ICP and the manual methods, is also presented, for a sufficient number of
      clinical CT-MR brain images. Finally, quantitative and qualitative results are
      also presented to validate the performance of these automatic surface-based
      registration schemes, in terms of consistency and accuracy. Throughout of this
      study, the automatic registration scheme comprising of the rigid transformation
      in conjunction with the Simulated Annealing method sequentially combined with the
      Powell method has been performed superior regarding all the other compared
      registration schemes.

PMID- 14600334
TI  - Biomechanical evaluation of the motor function of the thumb.
AB  - An experimental apparatus was developed to measure force production of a digit at
      various points of force application along the digit and in any direction within
      the transverse plane of the longitudinal axis of the digit. Eight normal subjects
      with asymptomatic hands were tested. Maximum voluntary isometric contraction
      forces were measured at the interphalangeal joint of the thumb in 16 directions
      that were evenly distributed within 360 degrees. Peak forces measured in all
      directions were used to create polar plots and to construct force envelopes using
      cubic spline interpolation. The areas of the force envelope and force quadrants
      were then calculated. The force produced by the thumb was dependent on the
      direction of force application. The highest force, 104.8 +/- 14.2 N, was
      generated in flexion, while the lowest force was generated in extension. The
      forces in extension, abduction and adduction were 24.8%, 57.2%, and 46.2% of the
      flexion force, respectively. Relatively high forces were generated in the
      directions of flexion combined with abduction, and flexion combined with
      adduction. The area of the entire force envelope was found to be 12,142 +/- 3,149
      N-N. The percentage quadrant areas, relative to the total force envelope area,
      for extension-adduction, extension-abduction, flexion-abduction, and flexion
      adduction were 7.8%, 11.4%, 39.3%, and 41.4%, respectively. The percentage
      quadrant areas for extension, abduction, flexion, and adduction were 4.9%, 23.6%,
      52.7%, and 18.8%, respectively. The current study provides a more advanced and
      comprehensive method for quantification and investigation of the motor function
      of the thumb, which has potential in clinical applications for diagnosis of hand
      disorders, evaluation of deterioration or improvement of hand motor function, and
      guidance of therapeutic and surgical intervention.

PMID- 14600335
TI  - Fixation response of two cementless tibial implants under static and fatigue
      compression loading.
AB  - The short- and long-term success of tibial cementless implants depend on the
      initial fixation stability often provided by posts and screws. Excessive relative
      interface motions are known to inhibit bone ingrowth and, hence, biologic
      fixation. In the present study, the stability of two cementless tibial implants
      under static and cyclic loading was studied. An apparatus was developed to
      perform compression tests on tibial components fixed by screws or posts onto
      resurfaced tibiae. Motion transducers were placed to record liftoff and
      subsidence displacements. A load of 1000 N was eccentrically applied on the
      medial plateau via the femoral component. The response was measured under static
      and repetitive loading up to 4000 cycles at 1 Hz. Experimental results showed
      that the screw fixation yielded the stiffer response and, hence, provided greater
      initial stability. The tibial component fixed with posts demonstrated larger lift
      off displacements. Comparison of measured results of static tests before and
      after fatigue indicated that the load-displacement behavior was not significantly
      affected by the cyclic fatigue loading under 1000 N up to 4000 cycles at 1 Hz.
      Nevertheless, much larger permanent displacements were recorded for the post
      fixation systems. In contrast to screw fixation, posts fixation systems
      demonstrated marked deterioration under larger compression loads of approximately
      2000 N.

PMID- 14600336
TI  - Quantitative forearm muscle strength influences radial bone mineral density in
      osteoporotic and healthy males.
AB  - Fractures are not rare in male osteoporosis and bone mineral density (BMD)
      measurement is used in the diagnosis and monitoring, preventing and/or treating
      the disease. Muscle strength and BMD are highly related to each other. The distal
      radius is one of the most common sites of osteoporotic fractures. The
      relationship of quantitative muscle strength and BMD of the forearm has not yet
      been established. The objective of this study was to assess forearm muscle
      strength and grip strength in relation to BMD in 46 osteoporotic and randomly
      selected 45 healthy male participants. Forearm muscle strength and BMD were
      quantitatively measured using an isokinetic dynamometer and dual-energy-X-ray
      absorptiometry (DEXA), respectively. Significant correlation was found among the
      muscle strength and dominant forearm BMD in 60 and 120 deg/s velocities. In the
      non-dominant arm, the 120 deg/s velocity was only significantly positively
      correlated to forearm BMD. Pearson's Product coefficient presented a moderate
      correlation between muscle strength and BMD at the dominant arms of both groups,
      whereas, the difference in the non-dominant forearm came from the difference of
      usage frequency. In conclusion, quantitative forearm muscle strength and BMD is
      moderately correlated and exercise can be advised to prevent distal radius
      fractures in male osteoporosis.

PMID- 14600337
TI  - Oxygen tension modulates Ca2+ response to flow stimulus in endothelial cells
      exposed to hydrostatic pressure.
AB  - The effects of oxygen gas tensions and hydrostatic pressure on intracellular
      calcium, [Ca2+]i, response to a flow stimulus in endothelial cells were
      investigated. Cultured bovine aortic endothelial cells (BAECs) were exposed to a
      hydrostatic pressure of 100 mmHg under low oxygen gas tensions and were
      subsequently subjected to a 1 minute mechanical stimulation of fluid shear stress
      of 20 dynes/cm2. The [Ca2+]i response in BAECs was measured using a fluorescent
      indicator, Calcium Green-1. The maximum intensity for low oxygen tension was
      significantly lower than that for normal oxygen tension, which provides evidence
      that low oxygen tension regulates cellular functions downward. Moreover,
      preloading of hydrostatic pressure also reduced the increases in [Ca2+]i. These
      results suggest that BAECs in venous system, where oxygen tension and hydrostatic
      pressure are lower than those in arterial system, may be less sensitive to fluid
      flow. A separate observation showed that low oxygen tension did not significantly
      affect the cell morphology. In contrast, BAECs exposed to hydrostatic pressure
      showed marked elongation with no predominant orientation and the F-actin filament
      distributions were rearranged, indicating centrally located thick stress fibers.
      For better understanding of endothelial cell physiology, it is very important to
      elucidate the effect of oxygen gas tensions together with mechanical environment
      on endothelial cell responses.

PMID- 14600338
TI  - Quality analysis of medical device vigilance reports.
AB  - The quality of the notifications issued within the European Medical Device
      Vigilance system were retrospectively reviewed and the adequacy of the
      recommended guidelines evaluated. The study material comprised all 589 vigilance
      notifications the Finnish competent authority received from manufacturers and
      other national competent authorities during 1997, 1999, and 2001. The number of
      vigilance reports, particularly the reports issued by national competent
      authorities, has increased from 82 in 1997 up 166 in 2001 while the proportion of
      reports with demonstrated bearing on health risk has decreased from about 40%
      down to 20% during the last five years. The number of manufacturers' reports has
      also increased from 28 in 1997 up to 98 in 2001 while the information given in
      the reports have become somewhat more incoherent. The time needed to close a
      device-related incident has increased, too. It is obvious that the present
      vigilance guidelines provide adequate guidance for both the manufacturers and
      competent authorities to manage vigilance cases efficiently and appropriately. It
      is crucial that all pertinent parties should adopt the recommended procedures and
      act accordingly. The vigilance system underpinned with high quality notifications
      only assures the continuous enhancement of patient safety, the bottom line.

PMID- 14600339
TI  - Field flatness and symmetry of photon beams: review of the current
      recommendations.
AB  - Flatness and symmetry are main parameters determining the quality of a photon
      beam produced by linear accelerators. The quality assurance in routine clinical
      practice of radiotherapy and consequently the treatment-outcome depend definitely
      on the physical parameters of treatment-delivery. Several recommendations from
      national and international associations are reported. By reviewing the current
      literature and mainly according to the World Health Organization (WHO) report of
      quality assurance in radiotherapy, we may suggest that for flatness and symmetry,
      the optimal level of deviation should be within +/- 3%. Flatness and symmetry
      should be checked monthly or once a year in accordance to the guidelines of
      national societies.

PMID- 14600340
TI  - Recognition pattern of thyroglobulin autoantibody from hypothyroid dogs to
      tryptic peptides of canine thyroglobulin.
AB  - Circulating thyroglobulin autoantibody (TgAA) was analyzed using the Western
      immunoblot for determination of the dominant epitopes recognized by TgAA on
      tryptic peptides of canine thyroglobulin (cTg) in hypothyroid dogs. TgAA was
      measured in hypothyroid dogs, non-hypothyroid dogs with skin diseases and
      clinically normal dogs. Five of the 7 hypothyroid dogs, 1 of the 8 dogs with skin
      diseases and 1 of the 4 normal dogs were positive for TgAA. Four of the 5 TgAA
      positive hypothyroid dogs were Golden Retrievers, and 3 of them showed high
      antibody titers. The sera of TgAA positive-dogs reacted to several peptides, and
      their patterns varied from sample to sample. Sera from 3 dogs with high titers of
      TgAA reacted broadly to high molecular weight peptides ranging from 45 to 90 kDa.
      These Western immunoblot patterns of the sera were disappeared after pretreatment
      with sufficient amount of intact cTg. All serum samples of both TgAA positive
      dogs and negative controls reacted to low molecular weight peptides ranging from
      15 to 20 kDa. These immunoblot patterns of the sera were not disappeared even
      after pretreatment with sufficient amount of intact cTg. These findings show the
      possibility that the epitopes recognized by TgAA depend upon individual dogs with
      hypothyroidism and these autoantibodies recognize conformational epitopes on the
      cTg molecule.

PMID- 14600341
TI  - The effects of the loop diuretics furosemide and torasemide on diuresis in dogs
      and cats.
AB  - Torasemide is a new loop diuretic that combines the effects of furosemide and
      spironolactone. There are no reports on the effects of torasemide in cats and
      dogs. This study compared the diuretic effects of furosemide and torasemide in
      cats and dogs. Cats with pressure overload cardiac hypertrophy were given oral
      placebo, torasemide 0.3 mg/kg, or furosemide 1 mg/kg or 3 mg/kg. Control and
      mitral regurgitation dogs were given oral placebo, torasemide 0.2 mg/kg, and
      furosemide 2 mg/kg for 7 days. Urine samples were obtained at baseline and 1, 2,
      3, 4, 5, 6, 8, 12, and 24 hr after each drug dose. Urine volume and urine Na(+)
      and K(+) were measured. Both furosemide and torasemide increased urine volume 1
      hr after administration. Furosemide caused a dose-dependent increase in urine
      volume that peaked at 2-3 hr in cats and dogs. The diuretic effect of furosemide
      disappeared 6 hr after administration, while that of torasemide peaked 2-4 hr
      after administration and persisted for 12 hr in cats and dogs. In MR dogs,
      torasemide for 7 days significantly decreased urine potassium excretion. Plasma
      aldosterone increased with torasemide, whereas there was no change with
      furosemide. In conclusion, about 1/10 concentration of torasemide was as potent
      as furosemide and had a longer diuretic effect in cats and dogs. These data
      suggest that torasemide is useful for treating congestive heart failure or edema
      in cats and dogs.

PMID- 14600342
TI  - Isothermal amplification of rabies virus gene.
AB  - A sensitive and specific in situ amplification technique is needed to elucidate
      the dynamics of rabies virus in the body during the long incubation period after
      infection. To overcome the disadvantage of using the traditional reverse
      transcription (RT)-PCR in in situ studies, an isothermal nucleic acid sequence
      based amplification (NASBA) technique was developed for detection of the rabies
      virus gene. The NASBA technique involves the use of 4 enzymatic activities to
      produce multiple RNA copies of the target sequence by means of double-strand cDNA
      intermediates under an isothermal condition without thermocycling. The amplified
      cDNA intermediates from the genomic RNA in the rabies virion and the total RNA in
      the infected cells in NASBA reaction were analyzed by Southern hybridization
      assays. The specific amplified products of the rabies viral gene with the
      expected length were detected after 8 hr of incubation in NASBA using both of the
      RNAs as templates. The NASBA system used in this study was less sensitive than
      the general RT-PCR technique. This may have been because we employed Southern
      hybridization for the amplified cDNA intermediates, not many RNA copies, to
      evaluate the NASBA results. In conclusion, we successfully amplified the rabies
      viral gene in the NASBA reaction under an isothermal condition. The unique
      character of this technique would make it particularly valuable for in situ
      studies not only on rabies virus but also on other RNA viruses.

PMID- 14600343
TI  - Role of CXCR4 and SDF-1 in mammary tumor metastasis in the cat.
AB  - It has recently been suggested that the chemokine receptor CXCR4 and its ligand
      SDF-1 (CXCL12) promote metastasis of various cancers in humans. Since feline
      mammary tumors also metastasize to distant organs frequently, we used real-time
      quantitative PCR to examine the expression of feline CXCR4 (fCXCR4) in ten feline
      mammary tumor cell lines and seven feline mammary tumor tissues, and also the
      expression of feline SDF-1 (fSDF-1) in various organs. Cell lines derived from
      metastatic regions expressed more fCXCR4 than those derived from primary tumors.
      Mammary tumor tissues overexpressed more fCXCR4 than normal mammary tissues.
      Organs with high levels of fSDF-1 expression represent common sites of
      metastasis. Migration assays using the feline mammary tumor cell line NAC were
      also performed to test the activity of TN14003 and TC14012, antagonists of human
      CXCR4, to antagonize fCXCR4 expressed on NAC cells. TN14003 and TC14012 inhibited
      migration of NAC cells. We conclude that fCXCR4 may be a therapeutic target for
      feline mammary tumors.

PMID- 14600344
TI  - Effects of propofol-sevoflurane anesthesia on the maternal and fetal hemodynamics
      blood gases, and uterine activity in pregnant goats.
AB  - To determine the effects of propofol and sevoflurane on hemodynamics, acid-base
      balance and uterine activity in pregnant animals, a prospective experimental
      study was designed by use of ten pregnant goats. Propofol was intravenously
      administered at a bolus dose of 5 mg/kg and then infused a rate of 0.3 mg/kg/min
      for 5 min. Following the induction, the animals were incrementally inhaled 2.7
      and 4.1% of end-tidal concentration of sevoflurane each for 30 min, and then
      recovered. The maternal and fetal heart rate (HR), arterial blood pressure (BP)
      and acid-base balance, the intrauterine pressure (IUP), and the uterine blood
      flow (UBF) were measured. Following the pre-anesthetic data, the parameters were
      measured 7 times throughout the anesthetic and recovering periods. The propofol
      infusion induced 1.37 times of HR increase and produced decrease in PO(2) and a
      relevant metabolic acidemia in the mother, with no effect in the fetus.
      Sevoflurane reduced BP in the fetus from 30 (2.7%) to 60 (4.1%) min of
      inhalation. The uterine contractions disappeared throughout sevoflurane
      inhalation, and then recurred within 15 min after the cessation of sevoflurane.
      Propofol injection increases HR, and induces a moderate hypoxemia and metabolic
      acidemia associated with the suppressed ventilation for pregnant goats, with less
      effect on the fetal hemodinamics. Sevoflurane causes minimal change in maternal
      hemodynamics, but induces significant hypotension in the fetus and reduction of
      uterine activity. These data may be useful in making anesthetic choices combined
      with analgesia for Caesarian section in goats.

PMID- 14600345
TI  - The effects of twisting and type of aspiration needle on the efficiency of
      transvaginal ultrasound-guided ovum pick-up in cattle.
AB  - The effects of twisting and type (single- or double-lumen) of aspiration needle
      on the efficiency of transvaginal ultrasound-guided ovum pick-up (US-guided OPU)
      were investigated in cattle. The first study using slaughterhouse ovaries
      revealed that twisting of the needle during follicle aspiration improved the
      oocyte recovery rate without deleterious effects on the attachment of cumulus
      layers. Vacuum pressure affected the oocyte recovery and cumulus attachment,
      regardless of the needle type. The needle type did not affect the oocyte recovery
      or cumulus attachment with an optimized vacuum pressure. In the second study, US
      guided OPU was performed in live cows using two types of needles with a vacuum
      pressure of 75 mmHg. The needle type did not affect the oocyte recovery or
      cumulus attachment of the recovered oocytes. The results revealed that twisting
      of the needle is effective in follicle aspiration, and suggested that a single
      lumen needle is as useful as a double-lumen needle for US-guided OPU in cattle.

PMID- 14600346
TI  - Seasonal changes in spermatogenesis and testicular steroidogenesis in wild male
      raccoon dogs (Nyctereutes procynoides).
AB  - Testes of 15 wild adult male raccoon dogs (Nyctereutes procynoides) obtained from
      September 2000 to April 2001 were studied to clarify seasonal changes in
      spermatogenesis and testicular steroidogenesis. There were marked seasonal
      variations in the testis weight and size with values relatively low in September
      and highest in March. Spermatogonia and primary spermatocytes were observed in
      September, while spermatogonia, spermatocytes and round spermatids were present
      in January, and all types of spermatogenic cells including mature spermatozoa
      were found in the mating season (February and March). The number of spermatogenic
      cells reached their peak values in February and March. In addition, steroidogenic
      enzymes were immunolocalized using polyclonal antisera raised against bovine
      adrenal cholesterol side-chain cleavage cytochrome P450 (P450scc), human
      placental 3beta-hydroxysteroid dehydrogenase (3 betaHSD), porcine testicular
      17alpha-hydroxylase cytochrome P450 (P450c17), and human placental aromatase
      cytochrome P450 (P450arom). P450scc and P450c17 were identified in Leydig cells
      and spermatids in February, whereas these enzymes were present only in Leydig
      cells in September. 3betaHSD was found in Leydig cells in September and February
      with more intense staining in February. The localization of P450arom changed
      seasonally: no immunostaining in September; more extensive immunostaining in
      Leydig cells, Sertoli cells, and elongating spermatids in February. These results
      suggest that seasonal changes in the testis weight and size of wild male raccoon
      dogs are correlated with changes in spermatogenesis. Seasonal changes in
      testicular steroidogenesis suggest that the synthesis of androgen and estrogen
      reaches its peak in the mating season.

PMID- 14600347
TI  - Spermatogenesis, serum testosterone levels and immunolocalization of
      steroidogenic enzymes in the wild male Japanese black bear (Ursus thibetanus
      japonicus).
AB  - Twenty-one wild male Japanese black bears (Ursus thibetanus japonicus) were
      captured in the summer-autumn of 1998-2000 in the vicinity of Neo Village, Gifu
      Prefecture. Testes were measured, and testicular samples were biopsied and
      observed histologically. Four steroidogenic enzymes, i.e., cholesterol side-chain
      cleavage cytochrome P450 (P450scc), 3beta-hydroxysteroid dehydrogenase
      (3betaHSD), 17-alpha hydroxylase cytochrome P450 (P450c17), and aromatase
      cytochrome P450 (P450arom) were immunolocalized. Serum testosterone
      concentrations were measured by radioimmunoassay. Testis size changed little from
      1-3 years of age, increased rapidly at 4 years, and attained its peak at 5 years.
      Serum testosterone concentrations ranged from 0.05 to 1.78 ng/m l, and the mean
      +/- standard deviation was 0.43 +/- 0.48 ng/ml. Age of sexual maturation in wild
      male Japanese black bears was estimated to be 3-4 years. Seasonal changes in
      spermatogenesis were obvious; active in June, July and August, degenerated by
      September. Leydig cells, Sertoli cells and germ cells have the capability of
      synthesizing androgen, and Leydig cells, Sertoli cells, spermatids and
      spermatogonia have the capability of synthesizing estrogen in Japanese black
      bears.

PMID- 14600348
TI  - Successful use of an acceleration rate response pacemaker with a transvenous
      steroid-eluting screw-in lead for third-degree atrioventricular block in a
      labrador retriever.
AB  - Permanent pacemakers are commonly used in veterinary practice and can have a
      dramatic effect on the treatment of heart block. A Labrador Retriever dog
      suffering from exercise intolerance secondary to third degree atrioventricular
      block was treated with a new pacemaker system. A steroid-eluting screw-in type
      lead that has the advantage of being more fixed to the myocardial wall without
      increasing the pacing threshold was used. The heart rate was regulated with an
      acceleration sensing pacemaker generator that included several automatic
      modulation systems. Nineteen months after implantation, the dog has a normal
      level of activity. The present case suggests that this pacemaker design may offer
      important advantages for canine patients.

PMID- 14600349
TI  - Cytotoxicity for porcine islet cells by complement of six animal species.
AB  - Complement-mediated cytotoxicity for porcine islet cells (PICs) was evaluated
      using sera of six animal species. Then soluble complement receptor type-1 (sCR1)
      as an anti-complement agent was added to those sera, and the changes in 50%
      hemolytic unit of complement serum (CH50) and cytotoxic effect of those sera on
      PICs were examined. All the sera except for that of pig showed cytotoxicity.
      However, the extent of toxicity was considerably different between species. In
      the rat and human serum, sCR1 significantly reduced CH50 and cytotoxicity,
      however in the dog serum, sCR1 had no suppressive effects. These results may
      suggest that complement contribute to humoral cytotoxicity for PICs as a main
      factor, and the compatibility of complement with PICs differs between animal
      species.

PMID- 14600350
TI  - Molecular detection and characterization of Haemobartonella felis in domestic
      cats in Japan employing sequence-specific polymerase chain reaction (SS-PCR).
AB  - A novel PCR assay was developed in order to examine the prevalence of
      Haemobartonella felis (H. felis) in Japanese domestic cats and which was able to
      differentiate of the Ohio strain and the California strain of H. felis. Blood
      samples from a total of 21 cats suspected of having haemobartonellosis were
      examined employing a novel PCR assay and demonstrated positive results in 18 cats
      which was confirmed by cytological examination of blood smears. Four out of 18
      positive cats (22%) were infected with the California strain, whilst the other 12
      cats (67%) were infected with the Ohio strain and two animals (11%) were infected
      with both strains. As most of the cats with moderate to severe anemia were
      infected with the Ohio strain, it is suggested that the most prevalent strain of
      H. felis in Japanese domestic cats might be the Ohio strain. In the present
      study, it was thought that molecular detection and characterization of H. felis
      may provide valuable information regarding the severity and prognosis of this
      illness.

PMID- 14600351
TI  - Angiotensin converting enzyme and chymase activity in the feline heart and serum.
AB  - The feline cardiac and serum angiotensin converting enzyme (ACE) and chymase
      activities were determined and compared in dogs, and hamsters. In all three
      species, cardiac chymase activity exceeded ACE activity; however, there were some
      differences. In cats, left ventricular ACE and chymase activities (0.15 +/- 0.01
      and 0.59 +/- 0.1 mU/mg-protein, respectively) were lower than in dogs (0.42 +/-
      0.05: p<0.01 and 2.0 +/- 0.4 mU/mg-protein: p<0.01) and hamsters (0.93 +/- 0.06:
      p<0.001 and 2.1 +/- 0.2 mU/mg-protein: p<0.01); in contrast, serum ACE activities
      was higher in cats (12.7 +/- 1.0 mU/ml) than in dogs (5.9 +/- 0.6 mU/ml:
      p<0.001). The relative contribution of chymase (cats: 84.0 +/- 5.1%, dogs: 81.4
      +/- 3.4%, and hamsters: 72.6 +/- 5.6 %) to ANG-II formation in the heart was
      greater than that of ACE in these animals (cats: 10.9 +/- 4.1%, dogs: 11.5 +/-
      3.6%, and hamsters: 17.2 +/- 0.8%). These species-specific differences suggest
      that the efficacy of renin-angiotensin system modulating agents may differ among
      species.

PMID- 14600352
TI  - Three cases of canine gastrointestinal stromal tumors with multiple
      differentiations and c-kit-expression.
AB  - Three canine gastrointestinal stromal tumors (GISTs) were examined.
      Histopathologically, the tumor mass in the jejunum (Case 1) consisted of the
      proliferation of epithelioid cells with abundant eosinophilic or vacuolated
      cytoplasm. Gangliocyte-like or multinucleated giant cells were scattered. The
      tumor cells exhibited neural natures mimicking human gastrointestinal autonomic
      nerve tumors, which were immunopositive for several neuronal markers. Another
      jejunal mass (Case 2) was composed by a solid proliferation of spindle-shaped
      cells, arranging in interlacing fascicles and occasional storiform pattern. The
      tumor seemed to be classified undifferentiated GISTs, that showed no apparent
      neural or muscular features by ultrastructural and immunohistochemical
      examinations. In the pyloric mass (Case 3), the spindle cells having eosinophilic
      processes and elongated nuclei were arranged in sheets. Immunohistochemically,
      the tumor cells showed muscular natures as regards alpha smooth muscle actin and
      desmin expression.

PMID- 14600353
TI  - Properties of the tumor suppressor gene brca2 in the cat.
AB  - Mammary tumors are common in cats. As mutations in human Brca2 confer an
      increased risk of breast cancer, the full-length cDNA of the feline homologue of
      Brca2 was sequenced to obtain a basis for studying the relationship between its
      function and susceptibility to mammary tumors. The feline Brca2 cDNA is 10 kb
      long, and encodes 3,371 amino acids. The amino acid sequence of feline Brca2
      shares low homology with the Brca2 of other mammals, e.g., 53% homology with the
      murine protein. Analysis of the expression pattern of the feline Brca2 gene
      revealed that, as previously reported for other mammals, it is transcribed in
      various tissues, including the mammary gland.

PMID- 14600354
TI  - Vaccination against Fowlpox virus via drinking water.
AB  - The oral vaccination against Fowlpox was investigated via drinking water
      containing the F132-c strain of Fowlpox virus to be effective even though the
      vaccine virus-titer was 10(4) TCID (50)/dose each time. When the virus-titer of
      the F132-c strain was 10(4-5 )TCID(50)/dose per single drinking water
      vaccination, 90% or more of chickens were not protected, however, they were
      protected when vaccinated twice via drinking water. A weak immune response
      occurred by a slight infection after the first vaccination, and due to memory
      cells, a booster could work well after the second vaccination. These results
      suggest the possibility of reducing both the amount of virus required for a
      vaccine via drinking water and the labor cost in the field.

PMID- 14600355
TI  - Implantation of permanent transvenous endocardial pacemaker in a dog with
      atrioventricular block.
AB  - A 10-year old male mongrel dog was presented to the University Veterinary
      Teaching Hospital with a two-month history of episodic syncope. Twenty-four hr
      Holter electrocardiographic (ECG) recording revealed frequent episodes of
      advanced atrioventriculer block with long periods of ventricular asystole. The
      cause of syncope was determined to be Adams-Stokes syndrome exhibited
      bradyarrhythmia. After the animal failed to respond to medical therapy, permanent
      transvenous pacemaker implantation was performed. Postoperative Holter ECG showed
      100 beat per min programmed pacemaker rhythm, which indicated successful capture
      of the artificial pacing. The dog recovered smoothly from the operation and
      syncopal episodes completely disappeared. Six months after the surgery, no
      complications were observed and the dog's quality of life has dramatically
      improved.

PMID- 14600356
TI  - Changes in somal growth and dendritic patterns of the retinal ganglion cells in
      the chicks and chick embryos.
AB  - Changes in the somal growth and dendritic patterns of retinal ganglion cells
      (RGCs) were studied in early chick embryos and post-hatching chicks by means of
      the retrograde axonal transport labeling with DiI. Branching patterns of the
      dendrites were relatively uniform on E8 (embryonic day 8) and became more
      complicated on E11. Variety of the branching pattern became plainly abundant
      after E14. On the other hand, somata of RGCs continued to grow until E14,
      corresponding the appearance of the central-peripheral gradient of the somal
      size. After E14, RGCs elaborated on the formation of the dendritic patterns as
      found in chick retina, and simultaneously the growth of somal sizes almost
      ceased.

PMID- 14600357
TI  - Aspergillus niger pulmonary infection in a dog.
AB  - A 6-month-old male golden retriever was presented with fever, bloody-watery
      diarrhea and mild cough. Parvovirus and Isospora canis infection was confirmed
      and successfully treated. Two weeks later, the dog had severe cough and
      mucopurulent nasal discharge. Aspergillus niger was cultured from endotracheal
      washings on blood agar at 37 degrees C. Treatment with itraconazole for about 10
      weeks resolved the clinical signs.

PMID- 14600358
TI  - Effects of midazolam-butorphanol, acepromazine-butorphanol and medetomidine on an
      induction dose of propofol and their compatibility in dogs.
AB  - The effects of acepromazine-butorphanol (AB), midazolam-butorphanol (MB) and
      medetomidine (Med) on the induction dose of propofol and their compatibility with
      propofol were evaluated in client-owned dogs. All premedications induced good to
      excellent sedation and the induction dose of propofol was considerably reduced.
      Of the tested premedicants, Med induced the deepest sedation and the most potent
      dose-sparing effect. Induction of anesthesia was excellent to good in all dogs
      except for one dog premedicated with MB. Most dogs premedicated with AB or MB
      showed temporary apnea. Although other adverse effects such as bradycardia or
      hypotension may also occur, premedication with MB, AB or Med is a valuable
      technique for the induction of anesthesia with propofol in dogs in a clinical
      setting.

PMID- 14600359
TI  - Effects of Lepidium meyenii Walp and Jatropha macrantha on blood levels of
      estradiol-17 beta, progesterone, testosterone and the rate of embryo implantation
      in mice.
AB  - The effects of two Peruvian folk medicines, Lepidium meyenii Walp and Jatropha
      macrantha, on mouse sex steroid hormones and embryo implantation were
      investigated. Progesterone levels increased significantly in mice that received
      L. meyenii Walp, while testosterone levels increased significantly in mice that
      received L. meyenii Walp as well as in those that received both L. meyenii Walp
      and J. macrantha. However, there were no marked changes in blood levels of
      estradiol-17beta or the rate of embryo implantation.

PMID- 14600360
TI  - Three dogs under 2 years of age with heartworm caval syndrome.
AB  - Heartworm caval syndrome (CS) occurred in three dogs under 2 years of age. A 23
      month-old dog was recovered by surgical and medical treatments, but the other 2
      dogs (15 and 21 months old) died. Necropsy demonstrated 12 heartworms in the 15
      month-old dog and 8 worms in the 21-month-old dog. Histopathologically, pulmonary
      arterial embolism caused by dead worms and thrombi were observed in these cases.
      The findings suggested that CS could develop regardless of canine age and worm
      burden if pulmonary arterial embolism related to worm death or thrombus formation
      were induced.

PMID- 14600361
TI  - Survey on wild rodents for endoparasites in Iwate Prefecture, Japan.
AB  - Wild rodents (58 Apodemus speciosus, 29 A. argenteus and 7 Microtus montebelli)
      were surveyed for endoparasites in Iwate Prefecture, Japan, from October to
      December 1995 and from April to October 1996. Two trematodes (Echinostoma
      macrorchis, Plagiorchis muris), 4 or more cestodes (Hymenolepis diminuta,
      Raillietina coreensis, Cladothyridium spp., Cysticercus fasciolaris), 12
      nematodes (Carolinensis minutus, Eucoleus sp., Heligmosomoides kurilensis, H.
      protobullosus, H. speciosus, Heterakis spumosa, Rhabditis (Pelodera) orbitalis,
      Rictularia cristata, Syphacia emileromani, S. frederici, S. montana, Trichuris
      sp.) and 3 protozoans (Giardia sp., Trichomonas sp., Trypanosoma sp.) were
      identified. The two species of Apodemus were similar to each other, but they were
      extremely different from M. montebelli in parasite fauna.

PMID- 14600362
TI  - Optimum heat treatment conditions for masking the bitterness of the
      clarithromycin wax matrix.
AB  - The effects of the contents of aminoalkyl methacrylate copolymer E (AMCE) in a
      wax matrix on the mechanism of polymorphic transformation of glyceryl
      monostearate (GM) were clarified by evaluating the enthalpy change defined as
      1.51 (DeltaH(1)-DeltaH(2))/DeltaH(2), where DeltaH(1) and DeltaH(2) denote the
      enthalpies in the first and second thermal analyses, respectively. Using this
      value, K(1), the rate constant of transformation from alpha-form to beta'-form,
      and K(2), the rate constant of transformation from beta'-form to beta-form, could
      be obtained. As the ratio of AMCE increased, K(2) increased, but a minimum point
      existed for K(1). K(1) was always larger than K(2), but gradually approached K(2)
      as the ratio of AMCE increased. The optimum temperature for the transformation of
      GM was 50 degrees C, at which the enthalpy change was maximum. To prepare the wax
      matrix preparation of clarithromycin (CAM), we considered 40 degrees C the
      optimum treatment temperature for the transformation of GM in a CAM wax matrix
      compounded from CAM, GM and AMCE, since the matrices were mutually welded at
      above 45 degrees C during the spray congealing process. Although K(1) and K(2)
      were almost the same at 40 degrees C, the rate of transformation was accelerated
      by tumbling. By applying the tumbling that accelerated the transformation of GM
      in a CAM wax matrix, almost all of the alpha-form disappeared, and the release of
      CAM from the wax matrix diminished when the enthalpy change was more than 0.8.

PMID- 14600363
TI  - Alteration in the temperature-dependent content release property of
      thermosensitive liposomes in plasma.
AB  - The effect of plasma components on the temperature-dependent content release
      property of thermosensitive liposomes has been described. Temperature-sensitive
      liposomes containing mitomycin C (MMC) were prepared from
      dipalmitoylphosphatidylcholine (DPPC liposomes) and a 7 : 3 mixture of DPPC and
      dipalmitoylophosphatidylglycerol (DPPC/DPPG liposomes). We defined in this study
      the difference in the content release between 38 degrees C and 44 degrees C as an
      index of the temperature-dependent content release efficiency (Delta% release).
      In the absence of rat plasma, the Delta% release of the DPPC liposomes and the
      DPPC/DPPG liposomes was 83% and 71%, respectively. However, when the release
      study was conducted with rat plasma, the Delta% release increased to about 96%
      for both liposomes. In addition, while the DPPC liposomes were destabilized by
      rat plasma below the gel-to-liquid crystalline phase transition temperature
      (T(m)), MMC leakage from the DPPC/DPPG liposomes below T(m) was suppressed by rat
      plasma. Moreover, the plasma protein binding onto lipid bilayer was concomitant
      with the gel-to-liquid crystalline phase transition and then enhanced the
      temperature-dependent release from the DPPC/DPPG liposomes. The possible
      mechanism of interaction between liposomes and plasma proteins, especially serum
      albumin, was discussed based on differential scanning calorimetry and protein
      binding experiments.

PMID- 14600364
TI  - The anti-HBsAg (human type B hepatitis, surface antigen) and anti-HBeAg (human
      type B hepatitis, e antigen) C18 dibenzocyclooctadiene lignans from Kadsura
      matsudai and Schizandra arisanensis.
AB  - The C(18) dibenzocyclooctadiene lignans including three novel schizanrin F (1), G
      (2), H (3), along with the known kadsurarin (4), were isolated from Kadsura
      matsudai. A new C(19) homolignan named schiarisanrin E (5), together with the
      known C(18) lignans, gomisin B (6), G (7) and (+)-gomisin K(3) (8) were obtained
      from Schizandra arisanensis. Gomisin B, G and (+)-gomisin K(3) showed moderate to
      strong activity for antihepatitis in anti-HBsAg (human type B hepatitis, surface
      antigen) and/or anti-HBeAg (human type B hepatitis, e antigen) tests. The
      structural elucidations of new compounds 1-3 and 5 were based on two-dimensional
      (2D) NMR techniques including COSY, HMQC, HMBC, NOESY and CD spectra. Preliminary
      structure-activity relationship studies for these isolated lignans are also
      discussed.

PMID- 14600365
TI  - Identification and biological activity of microbial metabolites of xanthohumol.
AB  - Microbial transformation of xanthohumol using the culture broth of Cunninghamella
      echinulata NRRL 3655 afforded (2S)-8-[4"-hydroxy-3"-methyl-(2"-Z)-butenyl]-4',7
      dihydroxy-5-methoxyflavanone (5) and (2S)-8-[5"-hydroxy-3"-methyl-(2"-E)-butenyl]
      4',7-dihydroxy-5-methoxyflavanone (6). Xanthohumol (1) and flavanone 6 as well as
      (E)-2"-(2"'-hydroxyisopropyl)-dihydrofurano[2",3":4',3']-2',4-dihydroxy-6'
      methoxychalcone (2), (2S)-2"-(2"'-hydroxyisopropyl)-dihydrofurano[2",3":7,8]-4'
      hydroxy-5-methoxyflavanone (3) obtained with Pichia membranifaciens showed
      antimalarial activity against Plasmodium falciparum.

PMID- 14600366
TI  - The bitterness intensity of clarithromycin evaluated by a taste sensor.
AB  - The purpose of this study was to evaluate the ability of a quantitative
      prediction method using a taste sensor to determine the bitterness of
      clarithromycin powder suspensions of various concentrations and of a commercial
      clarithromycin dry syrup product (Clarith dry syrup, Taisho Pharmaceutical Co.,
      Ltd., Tokyo) containing aminoalkyl methacrylate polymer as a taste-masker. The
      bitterness of the clarithromycin dry syrup product dissolved in various beverages
      was also evaluated in gustatory sensation tests and using the taste sensor. In
      the sensor measurements, three variables were used to predict bitterness in
      single and multiple regression analysis: relative sensor output (R), the change
      of membrane potential caused by adsorption (CPA), and CPA/R ratio. The CPA values
      for channel 3 of the sensor predicted well the bitterness of clarithromycin
      powder suspensions and their filtered solutions. For Clarith dry syrup, the
      sensor output was small, suggesting that aminoalkyl methacrylate polymer was
      successful in almost complete masking of the bitter taste of the dry syrup
      product. When the bitterness intensities of mixtures of 1 g of Clarith dry syrup
      with 25 ml of water, coffee, tea, green tea, cocoa, milk, and a sports drink were
      examined, a good correlation was obtained between the results from human taste
      tests and the predicted values calculated on the basis of multiple regression
      analysis using CPA data from channel 4, and the CPA/R ratio from channel 3 of the
      taste sensor (r(2)=0.963, p<0.005). Co-administration of 1 g of Clarith dry syrup
      with an acidic sports drink was found to be the most bitter using either method.

PMID- 14600367
TI  - Preparation of new nitrogen-bridged heterocycles. 54.increased arene-arene
      interactions of 3-(bicyclic and tricyclic arylmethylthio)thieno[3,4-b]indolizine
      derivatives.
AB  - Some thieno[3,4-b]indolizine derivatives having a 1-naphthylmethylthio, 2-methyl
      1-naphthylmethylthio, 2-naphthylmethylthio, or 9-anthrylmethylthio group at the 3
      position were prepared and their intramolecular arene-arene interactions were
      investigated. In comparison with 3-(methylthio)thieno[3,4-b]indolizines which
      have no such interactions, the (1)H-NMR spectra of title compounds showed large
      high-field shifts (delta 0.06-0.89 ppm) for the protons of the pyridine ring in
      the thieno[3,4-b]indolizine, and these values were considerably larger than those
      (delta <0.3 ppm) in 3-(benzylthio)thieno[3,4-b]indolizines. The UV spectra also
      exhibited a characteristic absorption band near 425 nm attributable to the arene
      arene interaction. In the X-ray analyses of some compounds, however, the presence
      of both the gauche and the anti conformers at the sulfide spacer were confirmed.

PMID- 14600368
TI  - Interactions of cholesterol with cyclodextrins in aqueous solution.
AB  - The interaction of cholesterol with several cyclodextrins (CDs) was investigated
      in water using solubility method. It was found that heptakis (2,6-di-O-methyl)
      beta-CD (DOM-beta-CD) forms two types of soluble complex, with molar ratios of 1
      : 1 and 1 : 2 (cholesterol : DOM-beta-CD), and neither a soluble nor insoluble
      complex is formed between cholesterol and alpha-CD, beta-CD, and gamma-CD,
      although a minor soluble complex formation was observed between cholesterol and 2
      hydroxylpropyl-beta-CD. The thermodynamic parameters for 1 : 1 and 1 : 2 complex
      formation of cholesterol with DOM-beta-CD obtained from the changes in K with
      temperature are as follows: DeltaG degrees (1 : 1)=-11.6 kJ/mol at 25 degrees C
      (K(1 : 1)=1.09x10(2) M(-1)); DeltaH degrees (1 : 1)=-3.38 kJ/mol; TDeltaS degrees
      (1 : 1)=8.25 kJ/mol; DeltaG degrees (1 : 2)=-27.1 kJ/mol at 25 degrees C (K(1 :
      2)=5.68x10(4) M(-1)); DeltaH degrees (1 : 2)=-3.96 kJ/mol; and TDeltaS degrees (1
      : 2)=23.2 kJ/mol. The formation of the 1 : 2 complex occurred much more easily
      than that of the 1 : 1 complex. The driving force for 1 : 1 and 1 : 2 complex
      formation was considered to be mainly hydrophobic interaction. Also, based on the
      measurements of proton nuclear magnetic resonance spectra and studies with Corey
      Pauling-Koltun atomic models, the probable structutures of the 1 : 2 complex were
      estimated.

PMID- 14600369
TI  - Aggregation feature of fluorine-substituted benzene rings and intermolecular C
      H.F interaction: crystal structure analyses of mono- and trifluoro-L
      phenylalanines.
AB  - X-Ray crystal structures of four different fluorine-substituted phenylalanines
      (two mono- and two tri-substitutions) were analyzed to investigate the effect of
      fluorine atom on the association pattern of benzene rings. Although respective
      structures showed similar molecular packing in such a way that the layers of
      hydrophobic benzene rings and hydrophilic amino/carboxyl groups were alternately
      running along a crystallographic axis, the association patterns of benzene rings
      were different depending on the substitution position and number of fluorine
      atoms. The general features could be that the partially displaced face-to-face
      interactions are increased with increase in the number of fluorine atoms, whereas
      the edge-to-face interactions are decreased. The C-H bond next to a fluorine
      substituted carbon atom could serve as a donor of an intermolecular C-H.F
      hydrogen bond.

PMID- 14600370
TI  - Uncinoside A and B, two new antiviral chromone glycosides from Selaginella
      uncinata.
AB  - Five compounds have been isolated from the dried whole plants of Selaginella
      uncinata, two of them were new chromone glycosides, 5-hydroxy-2,6,8
      trimethylchromone 7-O-beta-D-glucopyranoside (uncinoside A) and 5-acetoxyl-2,6,8
      trimethylchromone 7-O-beta-D-glucopyranoside (uncinoside B). Their structures
      were elucidated by spectroscopic methods including one- and two-dimensional NMR
      techniques. The other three compounds were identified as 8-methyl eugenitol,
      amentoflavone and hinokiflavone. Uncinoside A and B showed potent antiviral
      activities against respiratory syncytial virus (RSV) with IC(50) value of 6.9 and
      1.3 microg/ml, moderate antiviral activities against parainfluenza type 3 virus
      (PIV 3) with IC(50) value of 13.8 and 20.8 microg/ml, respectively.

PMID- 14600371
TI  - Synthesis of glycosylcurcuminoids.
AB  - Condensation of glycosylated arylaldehyde with acetylacetone-B(2)O(3) complex
      gave a corresponding diglycosylcurcuminoid, and a similar reaction using a
      mixture of arylaldehyde and glycosylarylaldehyde gave an unsymmetrical
      monoglycosylcurcuminoid, both as boron-complexes. The boron was removed from the
      complexes by heating in methanol, thus achieving the synthesis of di- and mono
      glycosylcurcuminoids.

PMID- 14600372
TI  - Specific nonpeptide inhibitors of puromycin-sensitive aminopeptidase with a
      2,4(1H,3H)-quinazolinedione skeleton.
AB  - Potent, specific, chemically stable and non-peptide/small-molecular inhibitors of
      puromycin-sensitive aminopeptidase, such as 3-(2,6-diethylphenyl)-2,4(1H,3H)
      quinazolinedione (PAQ-22, 5), were prepared by the structural development of a
      potent PSA inhibitor, 2-(2,6-diethylphenyl)-1,2,3,4-tetrahydroisoquinoline-1,3
      dione (PIQ-22, 4). The design was carried out partly by applying electrostatic
      potential field information obtained from PIQ-22 (4) and its derivatives based on
      thalidomide (2). This information revealed that a positive electrostatic
      potential field around the benzylic methylene in the tetrahydroisoquinoline ring
      is necessary for potent activity. Lineweaver-Burk plot analysis showed that PAQ
      22 (5) and its derivatives inhibit puromycin-sensitive aminopeptidase (PSA) in a
      non-competitive manner. These potent and specific PSA inhibitors showed dose
      dependent cell invasion-inhibitory activity in a Matrigel assay using mouse
      melanoma B16F10/L5 cells, in spite of their low cell toxicity.

PMID- 14600373
TI  - A versatile route to 3-benzoheteroepines containing group 15 and 16 heavier
      elements involving several novel ring systems, and their thermal stabilities.
AB  - The C-unsubstituted 3-benzoheteroepines (2a-g) containing group 15 (P, As, Sb,
      and Bi) and group 16 (S, Se, and Te) heavier elements were prepared by the
      reaction of the corresponding metal reagents with (Z,Z)-o-bis(beta
      lithiovinyl)benzene (5) which was derived in two steps from a common o
      phthalaldehyde (3). The heteroepines (2) thus obtained were thermally labile
      towards heteroatom extrusion, and their half-lives on heating estimated from (1)H
      NMR spectral analysis showed that the 3-benzoheteroepines (2) were far less
      stable than the corresponding 1-benzoheteroepines (1). The 2,4
      bis(trimethylsilyl)-3-benzoheteroepines (17) containing Sb, Bi, and Te were also
      prepared from o-diiodobenzene (9) in 6 steps and were found to be more stable
      than the corresponding C-unsubstituted heteroepines (2).

PMID- 14600374
TI  - Molecular mobility of lyophilized poly(vinylpyrrolidone) and methylcellulose as
      determined by the laboratory and rotating frame spin-lattice relaxation times of
      1H and 13C.
AB  - Laboratory- and rotating- frame spin-lattice relaxation times (T(1) and T(1rho))
      of (1)H and (13)C in lyophilized poly(vinylpyrrolidone) (PVP) and methylcellulose
      (MC) are determined to examine feasibility of using T(1) and T(1rho) as a measure
      of molecular motions on large time scales related to the storage stability of
      lyophilized formulations. The T(1rho) of proton and carbon was found to reflect
      the mobility of PVP and MC backbones, indicating that it is useful as a measure
      of large-time-scale molecular motions. In contrast to the T(1rho), the T(1) of
      proton measured in the same temperature range reflected the mobility of PVP and
      MC side chains. The T(1) of proton may be useful as a measure of local molecular
      motions on a smaller-time-scale, although the measurement is interfered by
      moisture under some conditions. The temperature dependence of T(1) and T(1rho)
      indicated that methylene in the MC molecule had much higher mobility than that in
      the dextran molecule, also indicated that methylene in the PVP side chain had a
      higher mobility than that in the MC side chain.

PMID- 14600375
TI  - Computer-aided modeling of pentachlorophenol 4-monooxygenase and site-directed
      mutagenesis of its active site.
AB  - Homology modeling was used to construct a model of the three-dimensional
      structure of pentachlorophenol 4-monooxygenase (PcpB). A PSI-BLAST homology
      search was initially performed to identify the 3D structure of proteins
      homologous with PcpB. The feasibility of modeled structures of PcpB was evaluated
      by Verify3D, which calculated structural compatibility scores based on 3D-1D
      profiles. The predicted structure of PcpB had an acceptable 3D-1D self
      compatibility score, beyond the incorrect fold score threshold. A PcpB
      pentachlorophenol (PCP) complex was then constructed utilizing the modeled PcpB
      structure. After energy minimization of the complex, and successive minimizations
      of the system that consisted of the complex and the water layer surrounding the
      complex, the molecular dynamics of the system were simulated. The active-site
      residues of PcpB were identified on the basis of the modeled structure, and PcpB
      mutants were then designed to change the active site residues, expressed, and
      purified by affinity chromatography. The mutant activity was compared with that
      of the wild-type to investigate the validity of the modeled structure. The
      experimental results suggested that Phe85, Tyr216, and Arg235 were relevant to
      enzyme activity, and that Tyr397 and Phe87 were important for stabilization of
      the structure of PcpB.

PMID- 14600376
TI  - Arylnaphthalide lignans from Cleistanthus collinus.
AB  - Chemical examination of the aerial parts of Cleistanthus collinus afforded the
      arylanphthalide lignans, cleistanone (1), diphyllin (2), cleistanthins A (3), C
      (4) and D (5), and 4-O-(3"-O-methyl-beta-D-glucopyranosyl)-diphyllin (6). The
      first compound is a new member of the rare group of arylnaphthalide lignans
      containing an alkoxy group on the lactone ring. The structure of the compound was
      determined from its spectral data, chemical transformations and partial synthesis
      from diphyllin (2). The new lignan, 1 and its acetyl derivative, 7 were found to
      exhibit cytotoxicity against MT(2) cell lines.

PMID- 14600377
TI  - Eurycomaoside: a new quassinoid-type glycoside from the roots of Eurycoma
      longifolia.
AB  - A new C(19)-quassinoid-type glycoside has been isolated from the roots of
      Eurycoma longifolia. The structure elucidation of the compound was achieved by a
      combination of one- and two-dimensional NMR techniques, including (1)H-(1)H
      correlation spectroscopy (COSY), (1)H-(13)C-heteronuclear correlation
      spectroscopy (HMQC), and (1)H-(13)C-heteronuclear multiple-bond correlation
      spectroscopy (HMBC), as well as high resolution electrospray ionization Fourier
      transformation mass spectrometry (HR-ESI-FT-MS) data. The C(1)-glycosidation site
      in the quassinoid framework is encountered for the first time.

PMID- 14600378
TI  - Molecular weight determination of hypromellose phthalate (HPMCP) using size
      exclusion chromatography with a multi-angle laser light scattering detector.
AB  - The molecular weight of hypromellose phthalate (HPMCP), a polymer used for
      enteric coating, was determined using size exclusion chromatography with a multi
      angle laser light scattering detector. The values of weight-average molecular
      weight (Mw) of commercially available grades (HP-55, HP-55S, and HP-50) were
      45600, 60200, and 37900, respectively. Their inter-day precisions expressed in
      terms of the coefficient of variation were less than 3%. A correlation curve
      between Mw and solution viscosity was prepared so that Mw could be easily
      estimated from the solution viscosity measured by the compendial method.

PMID- 14600379
TI  - Synthesis and biological activity of sulfur-containing aryl-aldehyde Schiff
      bases.
AB  - A series of chemically modified aryl-aldehyde Schiff bases has been synthesized
      and tested for their antioxidant activity and radiation protection. We observed
      that disulfide-containing aryl-aldehyde Schiff base 6c exhibited potent free
      radical scavenging, antioxidation, and radioprotection activities.

PMID- 14600380
TI  - Fern constituents: dryocrassy formate, sitostanyl formate and 12alpha-hydroxyfern
      9(11)-ene from Cyathea podophylla.
AB  - Dryocrassyl formate, sitostanyl formate, and 12alpha-hydroxyfern-9(11)-ene were
      isolated from the fresh fronds of Cyathea podophylla. Their structures were
      elucidated by spectroscopic techniques and synthesis. Ten known triterpenoids,
      three derivatives of phytol, a stanol, and beta-tocopherol were also identified
      from this fern.

PMID- 14600381
TI  - Determination of polyacetylenes and ginsenosides in Panax species using high
      performance liquid chromatography.
AB  - A new HPLC method was developed to separate and identify three polyacetylenes
      (panaxynol, panaxydol and 1,8-heptadecadiene-4,6-diyne-3,10-diol) found in Panax
      species. The mobile phase was a linear gradient of 2 : 1 : 3 to 2 : 1 : 1 (v/v/v)
      methanol/acetonitrile/water in 40 min. HPLC analysis was performed at a flow rate
      of 1.5 ml/min with UV detection at 254 nm. The contents of the polyacetylenes and
      ginsenosides in Panax ginseng (white ginseng and red ginseng), P. quinquefolium,
      P. japonicus, and P. noteginseng were determined using these methods. The species
      containing the highest polyacetylene content (0.080%) was P. quinquefolium
      cultivated in Nagano, Japan. Meanwhile, the species with the highest ginsenoside
      content (9.176%) was P. noteginseng cultivated in Yunnan, China.

PMID- 14600382
TI  - Antitumor-promoting constituents from Chaenomeles sinensis KOEHNE and their
      activities in JB6 mouse epidermal cells.
AB  - Primary screening of antitumor-promoting activity using soft agar colony assays
      with JB6 cells was employed to isolate 22 compounds from Chaenomeles sinensis
      KOEHNE. These compounds were lyoniresinol-2a-O-alpha-L-rhamnopyranoside (1),
      lyoniresinol-2a-O-beta-D-glucopyranoside (2), aviculin (3), betulinic acid (4),
      betulin (5), 3-O-(E)-p-coumaroylbetulin (6), 3-O-(E)-caffeoylbetulin (7), 3-O-(Z)
      p-coumaroylbetulin (8), 3-O-(E)-caffeoyllupeol (9), alphitolic acid (10),
      sorbikortal II (11), tormentic acid (12), euscaphic acid (13), corosolic acid
      (14), maslinic acid (15), erythrodiol (16), 1-beta-D-glucopyranosyloxy-3,4,5
      trimethoxybenzene (17), avicularin (18), 7-O-beta-D-glucopyranosylkaempferol
      (19), 5-O-beta-D-glucopyranosylgenistein (20), 7-O-beta-D-glucopyranosylgenistein
      (21), epicatechin (22), and beta-sitosterol (23) and were identified using
      spectral data such as MS, (1)H- and (13)C-NMR. Compound 1, having a rhamnosyl
      group, showed greater activity than 2, having a glucosyl group, and 3, which was
      a bis-demethoxy derivative of 1. Betulinic acid (4), having a C-28 carboxyl
      group, 3-O-(E)-caffeoylbetulin (7), and tormentic acid (12) showed more potent
      activity than betulin (5), which has a C-28 hydroxymethyl group.

PMID- 14600383
TI  - A new naphthopyrone from the root of Pleuropterus ciliinervis.
AB  - A new naphthopyrone, pleuropyrone A (1), together with (-)-lyoniresinol 3a-O-beta
      D-glucopyranoside (2) and (+)-lyoniresinol 3a-O-beta-D-glucopyranoside (3) was
      isolated from the roots of Pleuropterus ciliinervis. The structure of
      pleuropyrone A (1) was determined to be 2,5-dimethyl-8-hydroxynaphthopyrone 10-O
      beta-D-glucopyranoside by spectroscopic methods including 2D-NMR. Compounds 2 and
      3 showed moderate antioxidant activity.

PMID- 14600384
TI  - Synthesis and antiviral activities of some 4,4'-dihydroxytriphenylmethanes.
AB  - 4,4'-Dihydroxytriphenylmethanes were synthesized using Bronsted acid or Lewis
      acid in yields of 24-86% as target compounds for developing antiviral agents.
      Most of the 4,4'-dihydroxytriphenylmethanes showed significant activity against
      herpes simplex virus type 1 (anti-HSV-1 activity) in a plaque reduction assay.
      Higher cytotoxicity was observed generally in halogenated 4,4'
      dihydroxytriphenylmethanes (2a-d) than in non-halogenated derivatives. The non
      halogenated derivative, 4,4',4"-trihydroxy-3"-methoxytriphenylmethane (3), showed
      remarkable antiviral activity with an EC(50) value of 1.8 microg/ml.

PMID- 14600385
TI  - Steroids from the underground parts of Trillium kamtschaticum.
AB  - Two 18-norspirostanol glycosides and an 18-norspirostanol, which were new
      compounds as natural products, have been isolated from the underground parts of
      Trillium kamtschaticum PALL. along with eight known steroidal glycosides. Their
      chemical structures were determined on the basis of spectroscopic data.

PMID- 14600386
TI  - Prenylated xanthones from Garcinia xanthochymus.
AB  - A new prenylated xanthone, 1,3,5,6-tetrahydroxy-4,7,8-tri(3-methyl-2
      butenyl)xanthone (1), was isolated from the wood of Garcinia xanthochymus
      together with a known xanthone, garciniaxanthone E (2). Their structures were
      determined by spectroscopic analysis. Compounds 1 (3 microM) and 2 (10 microM)
      elicited marked enhancement of nerve growth factor-mediated neurite outgrowth in
      PC12D cells.

PMID- 14600387
TI  - Two triterpenoid saponins from Neonauclea sessilifolia.
AB  - From the dried roots of Neonauclea sessilifolia (Rubiaceae), two new triterpenoid
      saponins, 3-O-beta-D-glucopyranosyl-(1-->2)-beta-D-quinovopyranosyl quinovic acid
      (1) and 3-O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D-quinovopyranosyl pyrocincholic
      acid 28-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester (2), were
      isolated, together with five known saponins. The structures of the new saponins
      were determined by spectroscopic and chemical means.

PMID- 14600388
TI  - Field survey of Glycyrrhiza plants in Central Asia (3). Chemical characterization
      of G. glabra collected in Uzbekistan.
AB  - The chemical characteristics of Glycyrrhiza glabra L. were investigated at a
      habitat in Uzbekistan. HPLC analysis of the underground parts indicated that
      glycyrrhizin contents varied from 3.3 to 6.1% of dry weight, and that glabridin,
      a species-specific flavonoid for G. glabra, was detected in all underground
      samples (0.08-0.35% of dry weight). HPLC analysis of the leaves indicated that G.
      glabra plants collected in the present study could be divided into two types, RT
      type and IQ-type, according to their major flavonol glycosides, rutin or
      isoquercitrin, respectively.

PMID- 14600389
TI  - Conversion of Ca2+ salt of an organic compound to its Li+ salt to simplify the
      fast atom bombardment mass spectrum.
AB  - The FAB mass spectrum of the Ca(2+) salt of RK-682 (1, MW 368), a potent protein
      tyrosine phosphatase inhibitor, shows a complex pattern due to Ca(2+) adduct ions
      with multimers of 1 and their decomposition ions. Addition of LiCl greatly
      simplified the FAB mass spectrum, providing a prominent Li(+) adduct ion of 1 at
      m/z 381 [M+2Li-H](+). The addition of LiCl also greatly simplified the FAB mass
      spectrum of calcium pantothenate. This approach may be generally useful for
      molecular weight determination of multivalent metal salts of organic compounds,
      or organic compounds that can form Li salts, by FAB mass spectrometry.

PMID- 14600390
TI  - Biomimetic oxidation of curcumin with hydrogen peroxide catalyzed by 5,10,15,20
      tetraarylporphyrinatoiron(III) chlorides in dichloromethane.
AB  - The biomimetic oxidation of curcumin, a main turmeric pigment with hydrogen
      peroxide catalyzed by different 5,10,15,20-tetraarylporphyrinatoiron(III)
      chlorides [TAPFe(III)Cl] in dichloromethane has been studied to give a C-C
      coupled curcumin dimer in 40-70% yield. The structure of the dimer has been
      elucidated by (1)H-, (13)C-NMR, IR and FAB-Mass spectroscopic data.

PMID- 14600391
TI  - Controlled release of vitamin E from thermo-responsive polymeric physico-gel.
AB  - Thermo-sensitive copolymer consists of poly(2-ethoxyethyl vinyl ether) and
      poly(hydroxyethyl vinyl ether) (EOVE200-HOVE400), whose sol-gel transition
      temperature was 20.5 degrees C, was synthesized and its applicability to a drug
      delivery system was examined. Vitamin E (VE) was enclosed in EOVE200-HOVE400 and
      the release of VE was measured by varying the temperature 10<-->30 degrees C.
      There was no release of VE from EOVE200-HOVE400 at 30 degrees C, while VE was
      released when the temperature was reduced to 10 degrees C.

PMID- 14600392
TI  - Oxidation of ferulic acid by Momordica charantia peroxidase and related anti
      inflammation activity changes.
AB  - Plant peroxidases were found to play an important role in plant physiology such
      as the metabolism and transformation of small complexes. In the present research,
      a novel Momordica charantia peroxidase (MCP) from fruits was purified to
      electrophoretic homogeneity by combining consecutive treatment of ammonium
      sulfate fractionation, ion exchange chromatography on DEAE-Sepharose FF, affinity
      chromatography on concanavalin A (Con A) Sepharose and gel filtration on Sephadex
      G-150. The physical and chemical characters of MCP were also investigated. MCP
      catalyzed the oxidation of ferulic acid (FA) to dehydrodimer (FA-2) in aqueous
      acetone system at pH 5.0. Its structure was identified by spectral analyses
      including IR, 1H-, 13C-NMR and electrospray ionization mass spectroscopy (ESI
      MS). The anti-inflammatory activities of FA, FA-2 and other derivatives were
      examined. FA-2 significantly inhibited the release of proinflammatory factors
      such as TNF-alpha, NO and proliferation of spleen cells induced by
      phytohemagglutinin (PHA) and Con A and promoted a greater DNA fragmentation of
      spleen cells than that of other complexes. These results suggested that MCP as a
      tool enzyme transformed some complexes such as FA to more active derivatives, and
      that FA-2 was a potential inhibitor on inflammation through interference with
      immune response in the process of inflammation, which maybe was associated with
      apoptosis of immune related cells induced by FA-2.

PMID- 14600393
TI  - Proteomic analysis of proteins that binds specifically to the homologous repeat
      regions of white spot syndrome virus.
AB  - White spot syndrome virus (WSSV) is a major pathogen in the cultivated shrimp.
      Nine homologous repeat regions (hrrs) have been reported interspersed throughout
      the WSSV genome. In this investigation, the protein fraction that specifically
      bound to the hrrs was isolated by using DNA-affinity chromatography. A total of 9
      (S1 to S9) and 5 (C1 to C5) proteins separated from the WSSV infected shrimp and
      the healthy shrimp, respectively, were detected by using two-dimensional
      polyacrylamide gel electrophoresis, and 6 proteins changed with WSSV infection
      were analyzed by mass spectrometry (MS). One (S4) of the 6 proteins examined was
      identified as WSSV ORF59 protein, and another (S3) was a shrimp arginine kinase.
      No homologous proteins were found with the remaining 4 proteins by searching in
      the WSSV ORF database and NCBI database. The specific binding site of the 6
      proteins was then determined by gel mobility shift assay (GMSA). Temporal
      analysis revealed that ORF59 gene was transcribed at the early stage of the
      infection. The results we obtained provide important information to understand
      WSSV replication. The combination of DNA-affinity chromatography, 2D-PAGE and MS
      approaches should have general application to the identification of gene
      regulating proteins of WSSV. The results represent the first isolation of a set
      of proteins that bind to the hrrs, and, furthermore, lead us a new research
      direction for the prevention and the therapy of WSSV.

PMID- 14600394
TI  - The behavior of dihydropyrazine with DNA strand-breakage activity in vivo.
AB  - The effects on the viability of cell lines treated with 2,3-dihydro-5,6
      dimethylpyrazine and its derivatives, which revealed DNA strand-breakage activity
      by the generation of radicals in vitro, were recognized from certain
      morphological changes and the detection of apoptosis-related proteins: cleaved
      PARP and SAPK/JNK. These results would suggest that sugar-derived
      dihydropyrazines induce changes in the cells of certain organs and cause various
      internal injuries in vivo. The biodistribution of 14C-labelled 2,3-dihydro-5,6
      dimethylpyrazine was studied in mouse and the autoradiograms showed highly
      contrasting results. Radioactivity was high in the brain, spinal cord, salivary
      gland, and thymus and low in the heart, stomach, and blood. The result was
      supported by the activity (% dose per organ).

PMID- 14600395
TI  - Hydrolysis of synthetic substrate, L-pyroglutamyl p-nitroanilide is catalyzed
      solely by pyroglutamyl aminopeptidase I in rat liver cytosol.
AB  - Pyroglutamyl aminopeptidase I (PAP-I) is a cytosolic cysteine peptidase, which
      hydrolytically removes the L-pyroglutamate residue from the amino terminus of
      endogenous proteins and peptides. L-Pyroglutamyl p-nitroanilide serves as the
      synthetic substrate of this enzyme, while there is a possibility of other
      hydrolases being involved in the hydrolysis of this xenobiotic substrate. We
      cloned a full-length cDNA encoding rat PAP-I from a rat liver cDNA library and
      expressed this cDNA in Escherichia coli to obtain a recombinant PAP-I as a single
      protein. The cDNA encoded a sequence of 209 amino acids with a calculated
      molecular weight of 22913 Da. The homology of the deduced amino acid sequence of
      rat PAP-I was 98.6 and 94.3% to mouse and human PAP-Is, respectively. The
      biochemical properties of the recombinant rat PAP-I were almost identical to
      those of the recombinant mouse and human PAP-Is and the purified rat liver
      cytosolic PAP-I in terms of the molecular weight, subunit structure, affinity to
      the substrate, inhibitor profile and pH optimum. Immunoblot analysis using an
      antibody raised against recombinant rat PAP-I showed that rat PAP-I is present
      almost exclusively in the cytosolic fraction of the rat liver. Moreover, the
      hydrolyzing activity for L-pyroglutamyl p-nitroanilide in rat liver cytosolic
      fraction was completely inhibited by the antibody, strongly suggesting that this
      xenobiotic substrate is hydrolyzed solely by PAP-I.

PMID- 14600396
TI  - Antioxidant activity of Caesalpinia sappan heartwood.
AB  - Antioxidant activity of Caesalpinia sappan heartwood was studied both by in vitro
      and in vivo models. The ethyl acetate, methanol and water extracts exhibited
      strong antioxidant activity as evidenced by the low IC50 values in both 1,1
      diphenyl-2-picryl hydrazyl (DPPH) and nitric oxide methods. The values were found
      to be less or comparable to those of ascorbic acid and rutin, the standards used.
      Administration of the successive methanol and water extracts at 50 and 100 mg/kg
      body weight given for four days prior to carbon tetrachloride (CCl4) treatment
      caused a significant increase in the level of superoxide dismutase (SOD) and
      catalase and a significant decrease in the level of thiobarbituric acid reactive
      substances (TBARS), when compared to CCl4 treated control in both liver and
      kidney. These changes observed at 100 mg/kg body weight treatment were comparable
      to those observed for standard vitamin E at 50 mg/kg treatment. The results
      support significant antioxidant nature of Caesalpinia sappan heartwood extracts.

PMID- 14600397
TI  - Effects of chronic treatment with a water-alcohol extract from Erythrina mulungu
      on anxiety-related responses in rats.
AB  - We investigated the effects of chronic oral treatment with a water-alcohol
      extract from the inflorescence of Erythrina mulungu (Leguminosae-Papilionaceae)
      (EM, 50, 100, 200 mg/kg) in rats submitted to different anxiety models: the
      elevated T-maze (ETM, for inhibitory avoidance and escape measurements), the
      light/dark transition, and the cat odor test. These models were selected for
      their capacity to elicit specific subtypes of anxiety disorders as recognized in
      clinical practice. Treatment with EM impaired inhibitory avoidance latencies in a
      way similar to the reference drug, diazepam (DZP). Additionally, both EM and DZP
      increased the number of transitions and the time spent in the lighted compartment
      of the light/dark transition model. Furthermore, neither EM nor DZP altered
      behavioral responses of rats to a cloth impregnated with cat odor. In contrast to
      DZP, however, EM also altered ETM one-way escape. These results were not due to
      motor alterations since no significant effects were detected in the number of
      crossings or rearings in the arena. The present observations suggest that chronic
      EM exerts anxiolytic-like effects in defensive behaviors related to generalized
      anxiety and panic disorder. Although alkaloids appear to be one of the main
      constituents of EM, the possible mechanisms through which the extract exerts its
      anxiolytic action should be further investigated.

PMID- 14600398
TI  - Intracellular regulation of evodiamine-induced A375-S2 cell death.
AB  - We have reported that in A375-S2 cells, evodiamine isolated from Evodia
      rutaecarpa induces cell death of human melanoma, A375-S2, through two distinct
      pathways: apoptosis and necrosis. In the present study, we further demonstrate
      two different mechanisms by which evodiamine induces apoptosis and necrosis.
      Although caspase-1 and -10 inhibitors failed to block cell death, pan-caspase
      inhibitor and caspase-3, -8, and -9 inhibitors had marked inhibitory effects on
      apoptosis induced by 15 microM evodiamine. Furthermore, evodiamine-induced
      activation of caspase-3 resulted in the down-regulation of anti-apoptotic Bcl-2
      expression and up-regulation of proapoptotic Bax expression. After 24 h
      incubation with evodiamine, no caspase inhibitor had any influence on cell death,
      but p38 mitogen-activated protein kinase (MAPK) inhibitor (SB203580) attenuated
      cell death; in contrast, extracellular signal-regulated protein kinase (ERK) MAPK
      inhibitor (PD98059) augmented cell death, as was further confirmed by cotreatment
      with SB203580 or PD98059 and pan-caspase inhibitor. Moreover, evodiamine
      increased the phosphorylation of p38 and decreased the expression and
      phosphorylation of ERK in caspase-independent necrosis. Consequently, evodiamine
      induced the caspase- and Bax-mediated apoptosis at an early stage, but, initiated
      MAPKs-dependent necrosis at a later stage.

PMID- 14600399
TI  - Alpha 2-adrenoceptor modulates the release of acetylcholine from the rostral
      ventrolateral medulla in response to morphine.
AB  - The present study examined the role of the noradrenergic system in the modulation
      of acetylcholine (ACh) release in the rostral ventrolateral medulla (RVLM) using
      in vivo microdialysis of morphine. The basal level of ACh was 325.0 +/- 21.1
      fmol/20 microl/15 min in the presence of neostigmine (10 microM). Intraperitoneal
      (i.p.) administration of 5 and 10 mg/kg morphine significantly increased ACh
      release by the RVLM. This enhancement was reversed by naloxone (1 mg/kg, i.p.).
      In addition, pretreatment with yohimbine (0.5 mg/kg, i.p.) or prazosin (0.2
      mg/kg, i.p.) attenuated the systemic morphine-induced release of ACh in the RVLM.
      However, propranolol (0.2 mg/kg, i.p.) did not affect the morphine-induced ACh
      release. The addition of morphine (10(-4) M) to the perfusion medium increased
      the ACh release by 72.4% of the predrug values. The increased ACh release induced
      by local application of morphine was attenuated by pretreatment with yohimbine,
      but not prazosin. These findings suggest that morphine exerts an indirect
      stimulatory effect on the release of ACh by the RVLM and that the morphine
      induced increase in ACh release is modulated by alpha2-adrenoceptors in freely
      moving rats.

PMID- 14600400
TI  - Pharmacological activity of deep-sea water: examination of hyperlipemia
      prevention and medical treatment effect.
AB  - When normal rabbits were administered various samples of deep-sea water, their
      biochemical values changed within normal limits, and no differences from
      distilled water administration (control) group levels were observed. Furthermore,
      no histopathological changes were observed in internal organs on the 28th day
      after administration. The serum total cholesterol (T-Cho) and low density
      lipoprotein cholesterol (LDL-Cho) levels of normal rabbits fed with a 1%
      cholesterol-containing diet simultaneously administered deep-sea water
      (desalinated water, hardness 28, 300, and 1200) increased with time up to about
      1500 mg/dl. However, the degrees of increase were smaller than those of the
      control group, which received distilled water. Furthermore, when prepared
      hyperlipemia rabbits were administered deep-sea water (desalinated water,
      hardness 28, 300, and 1200), there were no significant changes in aspartate
      aminotransferase (AST), alanine aminotransferase (ALT), high density lipoprotein
      cholesterol (HDL-Cho), or triglyceride (TG) levels. On the other hand, T-Cho and
      LDL-Cho levels were reduced when the rabbits were changed to normal food, and the
      degree of reduction was more than that of the control group. In the liver and
      main artery bow, as the hardness of the deep-sea water increased, the
      accumulation of lipid and permeation of macrophages was reduced. This result was
      well in agreement with the results of the T-Cho and LDL-Cho levels. From these
      results, it is clear that deep-sea water controls the increase of serum lipid
      values (T-Cho and LDL-Cho) of cholesterol-fed rabbits, and promotes the reduction
      of serum lipid hyperlipemia rabbits. The minerals in deep-sea water greatly
      influence this effect.

PMID- 14600401
TI  - The induction of long-term potentiation at amygdalo-hippocampal synapses in vivo.
AB  - Electrical stimulation of the basolateral amygdala (BLA) evoked synaptic
      potentials in the dentate gyrus (DG) of the hippocampus in anesthetized rats. To
      determine if this pathway possesses synaptic plasticity, we investigated the
      impact of several conditions of high-frequency stimulation on BLA-DG synaptic
      potentials in these rats. Application of two trains of 100-pulse, 100-Hz
      stimulation or theta-burst stimulation to the BLA reproducibly induced long-term
      potentiation (LTP) of BLA-DG synaptic potentials. Paired-pulse facilitation was
      unchanged during LTP, suggesting that postsynaptic mechanisms are involved in the
      expression of LTP. In addition, the induction of LTP was not affected by the N
      methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonovalerate,
      suggesting that activation of NMDA receptors is not required. This novel form of
      LTP should be a valuable model for elucidating neural mechanisms underlying the
      formation of emotional memory.

PMID- 14600402
TI  - Bone anabolic effects of S-40503, a novel nonsteroidal selective androgen
      receptor modulator (SARM), in rat models of osteoporosis.
AB  - A novel nonsteroidal androgen receptor (AR) binder, S-40503, was successfully
      generated in order to develop selective androgen receptor modulators (SARMs). We
      evaluated the binding specificity for nuclear receptors (NRs) and osteoanabolic
      activities of S-40503 in comparison with a natural nonaromatizable steroid,
      5alpha-dihydrotestosterone (DHT). The compound preferentially bound to AR with
      nanomolar affinity among NRs. When S-40503 was administrated into orchiectomized
      (ORX) rats for 4 weeks, bone mineral density (BMD) of femur and muscle weight of
      levator ani were increased as markedly as DHT, but prostate weight was not
      elevated over the normal at any doses tested. In contrast, DHT administration
      caused about 1.5-fold increase in prostate weight. The reduced virilizing
      activity was clearly evident from the result that 4-week treatment of normal rats
      with S-40503 showed no enlargement of prostate. To confirm the bone anabolic
      effect, S-40503 was given to ovariectomized (OVX) rats for 2 months. The compound
      significantly increased the BMD and biomechanical strength of femoral cortical
      bone, whereas estrogen, anti-bone resorptive hormone, did not. The increase in
      periosteal mineral apposition rate (MAR) of the femur revealed direct bone
      formation activity of S-40503. It was unlikely that the osteoanabolic effect of
      the compound was attribute to the enhancement of muscle mass, because immobilized
      ORX rats treated with S-40503 showed a marked increase in BMD of tibial cortical
      bone without any actions on the surrounding muscle tissue. Collectively, our
      novel compound served as a prototype for SARMs, which had unique tissue
      selectivity with high potency for bone formation and lower impact upon sex
      accessory tissues.

PMID- 14600404
TI  - Modulating effects of Korean ginseng saponins on ovarian function in immature
      rats.
AB  - The modulating effects of Korean ginseng saponins on ovarian functions were
      investigated in immature rats superovulated with pregnant mare serum gonadotropin
      (PMSG). A single dose of 1 mg (0.1 ml/head) of Korean ginseng total saponin
      (GTS), Korean ginseng protopanaxatriol saponin (GPT), Korean ginseng
      protopanaxadiol saponin (GPD), or ginsenoside-Rb1 (Gin-Rb1) was intravenously
      injected via jugular vein catheter three times at 1 h (early follicular phase),
      25 h (middle follicular phase), and 50 h (late follicular phase) after 30 IU PMSG
      administration. GPD and Gin-Rb1 significantly suppressed excessive ovulatory
      response caused by PMSG (p<0.05). All Korean ginseng saponins significantly
      improved oocyte quality by decreasing the proportion of abnormal oocytes
      (p<0.05). Gin-Rb1 significantly decreased preovulatory serum levels of androgens
      and 17beta-estradiol, while GPD increased preovulatory serum progesterone level
      (p<0.05). GPD significantly the increased postovulatory serum progesterone level
      (p<0.05). These results provide strong evidence that Korean ginseng saponins have
      a curative effect on ovarian dysfunction caused by excessive stimulation with
      PMSG.

PMID- 14600403
TI  - Synthesis and brain regional distribution of [11C]NPS 1506 in mice and rat: an N
      methyl-D-aspartate (NMDA) receptor antagonist.
AB  - NPS 1506 [3-fluoro-gamma-(3-fluorophenyl)-N-methylbenzenepropamine] is
      representative of a non-psychotomimetic class of N-methyl-D-aspartate (NMDA)
      receptor antagonists. [11C]NPS 1506 was prepared at high radiochemical purity
      (>98%) with a specific activity of around 50 GBq/micromol at the end of synthesis
      by methylation of the desmethyl precursor with [11C]methyl iodide in the presence
      of NaH. Biodistribution of [11C]NPS 1506 in mice and rat demonstrated that uptake
      into the brain was rapid and occurred at high levels. [11C]NPS 1506 showed no
      appreciable specific binding in rodent brains under in vivo conditions, possibly
      because of both a large non-specific bound fraction and low in vitro binding
      affinity for NMDA receptors.

PMID- 14600405
TI  - Antiallergic activity of ginsenoside Rh2.
AB  - The antiallergic activities of ginsenosides, which were isolated from acid
      treated ginseng (Panax ginseng, Araliaceae), and their metabolites by human
      intestinal bacteria were measured. Ginsenoside Rh2, which is a main metabolite,
      had the most potent inhibitory activity on beta-hexosaminidase release from RBL
      2H3 cells and in the passive cutaneous anaphylaxis reaction. The inhibitory
      activity of ginsenoside Rh2 was more potent than that of disodium cromoglycate, a
      commercial antiallergic drug. This compound showed membrane stabilizing action
      upon differential scanning calorimetry and inhibited nitric oxide (NO) and
      prostaglandin E2 (PGE2) in lipopolysaccharide-stimulated RAW cells. However, this
      ginsenoside Rh2 did not inhibit the activation of hyaluronidase and did not
      scavenge active oxygen. These results suggest that ginsenoside Rh2 can exhibit
      antiallergic activity originating from cell membrane-stabilizing activity and
      antiinflammatory activity by the inhibition of NO and PGE2 production.

PMID- 14600406
TI  - Restorative effect of repetitive administration of Shaoyao-Gancao-tang on
      bioavailability of paeoniflorin reduced by antibacterial synthetic drugs
      treatment in rats.
AB  - Paeoniflorin (PF) is an active glucoside in Shaoyao (peony root), and is
      transformed into an antispasmodic metabolite, paeonimetabolin-I (PM-I), by
      intestinal bacteria in the gut after oral administration of Shaoyao or Shaoyao
      Gancao-tang (SGT, Shakuyaku-Kanzo-To in Japanese). SGT is a pain-relieving
      traditional Chinese formulation (Kampo-medicine in Japanese) and is often used
      together with antibacterial synthetic drugs, such as amoxicillin and
      metronidazole (AMPC-MET), in peptic ulcer therapy. Since the bioavailability of
      PF in SGT has been reported to be significantly reduced by co-administered
      antibacterial drugs, we investigated how to minimize this reducing effect of
      antibacterial treatment in the present study. We found that repetitive
      administration of SGT starting 24 h after AMPC-MET treatment rapidly restored the
      plasma PM-I concentration from SGT reduced by AMPC-MET, due to its restorative
      effect on the decreased PF-metabolizing activity of intestinal bacteria in rat
      feces. The present findings suggest that it may be clinically useful to
      administer SGT repetitively, starting 1 or 2 d after treatment with a mixture of
      AMPC-MET during their combination therapy, to accelerate the recovery of the
      reduced bioavailability of PF in SGT. Similar administration regimens may also be
      useful in other combination therapies involving traditional Chinese formulations
      and antibacterial synthetic drugs to ensure the efficacy of the bioactive
      glycosides in the formulations.

PMID- 14600407
TI  - Decreased cyclosporin A concentrations in the absorption phase using
      microemulsion preconcentrate formulation in rats with cisplatin-induced acute
      renal failure.
AB  - Cyclosporin A pharmacokinetics was studied in rats with cisplatin-induced acute
      renal failure (ARF) using microemulsion preconcentrate (MEPC) and completely
      dissolved formulations. Although the pharmacokinetics of cyclosporin A was
      unchanged after intravenous administration, maximum concentration of cyclosporin
      A in ARF rats was significantly reduced to 608+/-62 and 999+/-189 ng/ml compared
      with 1720+/-142 and 1832+/-250 ng/ml in controls after oral administration of
      MEPC and completely dissolved formulations, respectively. In an in situ
      intestinal loop sac study, the amount absorbed plus metabolized and the blood
      concentration of cyclosporin A were similar between control and ARF rats, and
      taurocholic acid, one of the bile acids, significantly increased absorption of
      cyclosporin A using the MEPC formulation in both control and ARF rats; the amount
      absorbed plus metabolized with taurocholic acid was increased to 137 and 186%,
      and simultaneously the blood concentration was increased to 155 and 158% of that
      without taurocholic acid in control and ARF rats, respectively. The bile flow in
      ARF rats was decreased compared with that in controls. These results suggested
      that renal dysfunction decreased the absorption of cyclosporin A in spite of the
      MEPC formulation, and the alternation of bile secretion partly affected the
      absorption rate of cyclosporin A in the gastrointestinal tract.

PMID- 14600408
TI  - Participation of endogenous dehydroepiandrosterone and its sulfate in the
      pathology of collagen-induced arthritis in mice.
AB  - We have investigated the serum levels of dehydroepiandrosterone (DHEA) and DHEA
      sulfate (DHEAS) in type II collagen (CII)-induced arthritis (CIA) DBA/1J mice, an
      experimental model of human rheumatoid arthritis (RA). Serum levels of DHEA and
      DHEAS were measured by EIA and GC/MS, respectively. Sera were obtained from the
      mice on day 6, 13, 28 and 48 after the CII treatment. The disease onset of CIA
      was observed from day 28 (7%) to day 48 (80%) after CII immunization. The serum
      concentration of DHEA on day 13 did not differ from that on day 6 in CIA mice and
      untreated controls. Serum levels of DHEA on day 28 and 48 were significantly low
      compared with those on day 6 in controls. However, in CIA mice, DHEA levels on
      day 28 and 48 were not decreased from those on day 6. No difference in the serum
      DHEAS level on day 13 compared with day 6 was observed in either control or CIA
      mice. A significant decrease of DHEAS levels on day 28 and 48 compared with day 6
      was found in both groups. The time point for the retention of DHEA in CIA mice,
      day 28 and day 48, coincided with the disease onset of CIA. In conclusion,
      endogenous DHEA may be produced as a result of physiological response for the
      protection against CIA.

PMID- 14600409
TI  - In vitro anti-herpes simplex viruses and anti-adenoviruses activity of twelve
      traditionally used medicinal plants in Taiwan.
AB  - As an effort to search for new antiviral agents from traditional medicine, the
      hot water (HW) extract of twelve traditionally used medicinal plants in Taiwan
      was evaluated for their in vitro anti-herpes simplex viruses (HSV; including HSV
      1 and HSV-2) and anti-adenoviruses (ADV; including ADV-3, ADV-8 and ADV-11)
      activities with a XTT-based colorimetric assay. Results showed that the tested HW
      extracts exhibited anti-HSV and anti-ADV activities at different magnitudes of
      potency. Among the twelve medicinal plants, Boussingaultia gracilis var.
      pseudobaselloides (Basellaceae) and Serissa japonica (Rubiaceae) possessed broad
      spectrum of antiviral activity. Ardisia squamulosa (Myrsinaceae) and Artemisai
      princeps var. orientalis (Compositae) were more effective in inhibiting ADV-8
      replication than the other four viruses. Cell cytotoxic assay demonstrated that
      all tested HW extracts had CC50 values higher than their EC50 values. It was
      concluded that the twelve traditionally used medicinal plants in Taiwan possessed
      antiviral activity, and some of them merit further investigation.

PMID- 14600410
TI  - Quantitative measurement of biotin-binding immunoglobulin G in human sera using
      F(ab')2 anti-human IgG-coated multi-well plates.
AB  - Biotin-binding human immunoglobulin G (B-IgG) was quantitatively measured using
      an F(ab')2anti-human IgG-coated multi-well microplate for the first time. B-IgG
      was caught by F(ab')2anti-human IgG and was detected by the following detecting
      reagents: Peroxidase-labeled streptavidin, avidin and peroxidase-biotin, or
      avidin-biotinylated peroxidase complex with method A, B, or C, respectively.
      Commercially available B-IgG was detected by all these three methods. However,
      method A and B could not detect B-IgG in the human sera used in this study, but
      we quantitatively measured the B-IgG level using method C. The result is probably
      due to the fact that the sensitivity of method C was higher than that of methods
      A or B. Properties of B-IgG detected by method C are discussed in the text.

PMID- 14600411
TI  - Effects of Hange-koboku-to (Banxia-houpo-tang) on neuropeptide levels in human
      plasma and saliva.
AB  - Hange-koboku-to (Banxia-houpo-tang), a Chinese herbal (Kampo) medicine, has been
      used for improvement of hoarse voice, something foreign body sensation in the
      throat and/or esophagus, and swallowing reflex, among other conditions. One of
      the mechanisms of the empirical effects is assumed to be due to local changes in
      neuropeptide levels locally. We investigated the effects of Hange-koboku-to on
      neuropeptides, calcitonin gene-related peptide (CGRP), substance P, somatostatin,
      and vasoactive intestinal peptide (VIP) in plasma and saliva, as well as on
      salivary secretion in healthy subjects. A single oral administration of Hange
      koboku-to caused significant increases in substance P-immunoreactive substance
      (IS) (40 min) in plasma, and slightly increased in CGRP-IS and somatostatin-IS in
      plasma compared with placebo. In saliva neuropeptides, Hange-koboku-to caused
      significant increases in substance P-IS (20 min) and somatostatin-IS (40, 60
      min), and a slight increase in VIP-IS. However, a single Hange-koboku-to
      stimulation did not have a significant effect of sialosis volume. These results
      seem to suggest that Hange-koboku-to improves hoarse voice, something foreign
      body sensation in the throat and esophagus, and swallowing reflex disorder, by
      stimulation of neuropeptidergic nerves locally.

PMID- 14600412
TI  - Effect of 2,5-dimethylpyrazine on uterine contraction in late stage of pregnant
      female rats.
AB  - Effect of 2,5-dimethylpyrazine (2,5-DMP) on oxytocic agent-induced late pregnant
      uterine contraction in female rats was studied. Oxytocic agents induced
      hypercontraction in the late phase of pregnant uterine movements were inhibited
      by administration of 2,5-DMP. The inhibition of uterine contraction was obtained
      more strengthening by presence of a low dose of ritodrine hydrochloride than 2,5
      DMP alone. These results suggests that 2,5-DMP has an inhibitory action on
      uterine hypercontraction induced by oxytocic agent through the beta2-adrenoceptor
      in the pregnant uterus and supports the applicability of relaxing drugs for
      oxytocic agent-induced accidents.

PMID- 14600413
TI  - Effect of dried fruits of Solanum nigrum LINN against CCl4-induced hepatic damage
      in rats.
AB  - Ethanol extract of Solanum nigrum LINN was investigated for its hepatoprotective
      activity against CCl4-induced hepatic damage in rats. The ethanol extract showed
      remarkable hepatoprotective activity. The activity was evaluated using
      biochemical parameters such as serum aspartate amino transferase (AST), alanine
      amino transferase (ALT), alkaline phosphatase (ALP) and total bilirubin. The
      histopathological changes of liver sample in treated animals were compared with
      respect to control.

PMID- 14600415
TI  - Antimalarial activity of herbal extracts used in traditional medicine in Korea.
AB  - Aqueous extracts of 6 traditional Korean medicines used to treat malaria were
      tested in vitro for their antimalarial activity against Plasmodium falciparum.
      The EC50 values for the herbal extracts were in the range 1.4-8.1 microg/ml.
      Significant antimalarial activity was observed with Coptis japonica (EC50=1.4
      microg/ml), but it demonstrated no selective toxicity (selectivity=1). In
      contrast, Kalopanax pictus showed antimalarial activity (EC50=4.6 microg/ml) and
      higher selective toxicity (>4). This indicated that K. pictus may be potent for a
      new antimalarial agent.

PMID- 14600414
TI  - Carnosic acid, a component of rosemary (Rosmarinus officinalis L.), promotes
      synthesis of nerve growth factor in T98G human glioblastoma cells.
AB  - Nerve growth factor (NGF) is a factor vital for the growth and functional
      maintenance of nerve tissue. The authors found that a rosemary (Rosmarinus
      officinalis L.) extract enhanced the production of NGF in T98G human glioblastoma
      cells. Furthermore, the results indicated that carnosic acid and carnosol, which
      are major components of the rosemary extract, were able to promote markedly
      enhanced synthesis of NGF.

PMID- 14600416
TI  - Concentration-dependent atypical intestinal absorption of cyclic
      phenylalanylserine: small intestine acts as an interface between the body and
      ingested compounds.
AB  - Intestinal absorption of peptides in linear form has been studied extensively,
      but there is little knowledge of peptides in a cyclic form. In this report,
      intestinal absorption of cyclic phenylalanylserine (cyclo(Phe-Ser)), a precursor
      of gliotoxin, was studied in isolated rat small intestine as a model cyclic
      dipeptide. Absorption clearance (CLabs) decreased in the presence of
      glycylsarcosine, cephalexin or cephradine, substrates for H+/oligopeptide
      cotransporter (PEPT1). CLabs of cyclo(Phe-Ser) also decreased at 4 degrees C,
      thus indicating that cyclo(Phe-Ser) is in part transported by PEPT1. However, the
      Eadie-Hofstee plot of absorption revealed an atypical profile at lower
      concentrations of cyclo(Phe-Ser) (around 0.1 mM). Moreover, comparative
      experiments of absorptive and excretive transport showed that excretive transport
      from the serosal to mucosal side of isolated intestinal tissue at a 0.1 mM
      cyclo(Phe-Ser) was superior to absorptive transport from the mucosal side to the
      serosal side, and vice versa at a 1 mM cyclo(Phe-Ser). A kinetic model was
      constructed, in which cyclo(Phe-Ser) concentration for excretive transport was
      assumed to be at the binding site of excretive transporter, but not the unbound
      cytoplasmic concentration. These results as well as the results of kinetic
      analysis indicate that intestinal absorption consists of passive transport,
      carrier-mediated absorptive transport by PEPT1 and carrier-mediated excretive
      transport, resulting in atypical absorption. Although cyclic dipeptides have
      potentials as drugs, their intestinal absorption may be complex. The results of
      this study lead us to conclude that absorptive and excretive transport by the
      small intestine acts as an interface between the body and ingested compounds.

PMID- 14600418
TI  - Saturable absorption of glycerol in the rat intestine.
AB  - The permeability of glycerol, a small hydrophilic solute, across the intestinal
      membrane would be low, if passive diffusion restricted to the paracellular route
      is the principal transport mechanism as generally assumed for this class of
      solutes. However, in the present study using a closed loop of rat small intestine
      in situ, we found that the absorption of glycerol was faster than that of urea, a
      probe solute widely assumed to permeate exclusively via the paracellular route.
      This finding is inconsistent with the paracellular permeation hypothesis, which
      predicts that the absorption of glycerol, which is larger than urea in terms of
      molecular size, could not be faster than that of urea. We also found that
      glycerol absorption was saturable. These findings suggest the involvement of
      carrier-mediated transport in intestinal glycerol absorption. Glycerol absorption
      in the colon was also saturable, suggesting the involvement of carrier-mediated
      transport, although it was much slower than that in the small intestine. Carrier
      mediated glycerol transport might play an important role in absorbing glycerol
      liberated from dietary triglyceride. It would be interesting to further examine
      the possibility that a carrier-mediated glycerol transport system (or systems)
      might be involved in drug absorption and also that it might be utilized for oral
      drug delivery.

PMID- 14600417
TI  - Effect of Scutellariae radix extract on the high glucose-induced apoptosis in
      cultured vascular endothelial cells.
AB  - Endothelial cell apoptosis has been postulated as the initial trigger of the
      progression of microvascular disease in patients with diabetes mellitus. To
      investigate the role of Scutellariae radix extract, we examined its effect on the
      endothelial cell proliferation using the [3H]-thymidine incorporation method.
      Scutellariae radix extract significantly stimulated endothelial cell
      proliferation in a dose-dependent manner. We focused on the protective action of
      Scutellariae radix extract on the endothelial cell apoptosis induced by high
      glucose concentrations. Determination of endothelial cell apoptosis was performed
      using DNA gel electrophoresis, terminal deoxynuclotidyl transferase-mediated dUTP
      nick end-labeling (TUNEL) assay, and an ELISA kit. Exposure of vascular
      endothelial cell to high glucose (16.7 mM) for 72 h resulted in a significant
      increase in apoptosis, compared with the normal glucose concentrations (5.5 mM).
      Scutellariae radix extract inhibited high glucose-induced endothelial cell
      apoptosis. This result suggests that Scutellariae radix extract may contribute to
      antiapoptotic action against vascular endothelial cells, resulting in a
      beneficial effect in preventing diabetes-associated microvascular complications.

PMID- 14600419
TI  - Effect of quinine solutions on intracellular Ca2+ levels in neuro-2a cells-
      conventional physiological method for the evaluation of bitterness.
AB  - The purpose of the present study was to examine the effect of quinine on
      intracellular Ca2+ ([Ca2+]i) levels in cultured neuro-2a cells, and to
      investigate the possibility of using [Ca2+]i levels to predict the bitterness of
      quinine solutions. [Ca2+]i levels in neuro-2a cells increased following
      stimulation by quinine in a concentration-related manner. There was a good linear
      correlationship between the quinine-induced increase in [Ca2+]i levels increase
      and the bitterness scores of the quinine solutions as assessed in human gustatory
      sensation tests (r2=0.918). The quinine-induced increase in [Ca2+]i levels was
      inhibited by thapsigargin (an inhibitor of the Ca2+ pump into intracellular
      stores), U73122 (an inhibitor of phospholipase C) and omega-conotoxin (an N-type
      Ca2+-channel blocker), but not by nifedipine (an L-type Ca2+-channel blocker).

PMID- 14600420
TI  - Toll-like receptor-mediated activation of mast cells: implications for allergic
      disease?
AB  - Toll-like receptors have a critical role in innate immunity and host defence.
      However their role in allergic disease has not been studied in great detail. The
      presence of these receptors on mast cells opens up new possibilities concerning
      the role of Toll-like receptors in the pathogenesis of asthma and atopic
      dermatitis. The current review examines the biology of Toll-like receptors
      expressed on mast cells. In particular, mast cell expression of Toll-like
      receptors and the diverse responses observed following Toll-like receptor
      mediated activation are considered. Several pathogens such as Staphylococcus
      aureus and respiratory syncytial virus are known to contribute to the development
      or maintenance of allergic disease and also express potent activators of the Toll
      like receptor pathways. The importance of such interactions and the full role of
      pathogens in chronic allergic disease remain to be elucidated. The unusual
      ability of Toll-like receptor 2 activators to selectively induce leukotriene
      production by mast cells opens up new possibilities concerning mechanisms of
      disease exacerbation during infection.

PMID- 14600421
TI  - Pathomechanisms in celiac disease.
AB  - Celiac disease is a complex autoimmune disease which is characterized by a strong
      genetic association (HLA-DQ2 or -DQ8), gluten as nutritional etiological factor,
      and the enzyme tissue transglutaminase as endomysial autoantigen. Patients
      develop highly predictive IgA autoantibodies to tTG. Certain gluten peptides are
      presented by the disease-associated HLA-DQ2/DQ8 molecules leading to stimulation
      of gluten-specific T cells. This immune response which is driven in the lamina
      propria causes the mucosal transformation characteristic for celiac disease.
      Increased intestinal expression of tTG in patients with CD appears to play an
      important role in the pathogenesis of CD. Thus, modification of gluten peptides
      by tTG, especially deamidation of certain glutamine residues, can enhance their
      binding to HLA-DQ2 or -DQ8 and potentiate T cell stimulation. Furthermore, tTG
      catalyzed cross-linking and consequent haptenization of gluten with extracellular
      matrix proteins allows for storage and extended availability of gluten in the
      mucosa. New therapeutic approaches aim at proteolytic destruction of
      immunodominant gliadin peptides that are resistant to intestinal enzymes by
      bacterial prolyl endopeptidases, the inhibition of tTG activity with highly
      specific enzyme inhibitors or at HLA-DQ2/DQ8 blocking peptide analogues.

PMID- 14600422
TI  - Tuning of innate immunity and polarized responses by decoy receptors.
AB  - After the identification of the interleukin (IL)-1 type II receptor as the
      prototype, decoy receptors have been identified for a number of members of the IL
      1/IL-18, TNF, IL-10 and IL-13 receptor families. Moreover, the silent receptor D6
      is a promiscuous decoy and scavenger receptor of inflammatory chemokines. The IL
      1 decoy receptor is regulated by pro- and anti-inflammatory signals and its
      levels may serve as a readout of the activation of anti-inflammatory pathways,
      for instance by glucocorticoid hormones. Decoy receptors represent a strategy to
      tune inflammatory and polarized adaptive responses.

PMID- 14600424
TI  - A new glycoprotein allergen/antigen with the protease activity from Aspergillus
      fumigatus.
AB  - BACKGROUND: Aspergillus fumigatus is an opportunistic fungus causing allergic and
      invasive aspergillosis in humans and animals. It secretes an array of complex
      biologically active glycoprotein antigens and allergens. It is important to
      identify and characterize probable potential virulent factors playing a major
      role in the pathogenesis of aspergillosis. METHODS: Using protein purification
      techniques (lectin affinity chromatography, gel filtration, electroelution and
      high-pressure liquid chromatography), a major antigen/allergen with a molecular
      weight of 56 kD (gp56) from A. fumigatus was purified to homogeneity. The protein
      was characterized by immunoblot, ELISA and protease assays. The N-terminal amino
      acid sequencing was performed. RESULTS: The gp56 protein showed a single band on
      silver staining and isoelectric focussing. The protein to carbohydrate ratio was
      1.5:1 and gp56 gave a protein band at a molecular weight of 34 kD on enzymatic
      deglycosylation. It also exhibited IgG and IgE immunobinding with antibodies
      present in sera of allergic bronchopulmonary aspergillosis patients. The gp56
      exhibited protease activity and N-terminal seven-amino acid sequence showed
      homology with fungal serine proteases. CONCLUSIONS: The gp56 protein by virtue of
      its proteolytic activity could be one of the virulent factors of A. fumigatus
      involved in establishing infection in the host along with other factors.

PMID- 14600423
TI  - Identification of oilseed rape (Brassica napus) pollen profilin as a cross
      reactive allergen.
AB  - BACKGROUND: Major allergens of oilseed rape (OSR) pollen with molecular weights
      of 6/8, 14 and between 27 and 69 kD have been described. The aim of the present
      study was to further characterize the 14-kD allergen. METHODS: The 14-kD protein
      was purified from OSR pollen extracts by poly-(L-proline) (PLP)-Sepharose
      affinity chromatography and characterized immunologically by means of allergic
      patients' IgE antibodies, profilin-specific rabbit antisera, Western blot and
      ELISA inhibition using recombinant birch profilin (rBet v 2), and skin prick
      testing. RESULTS: By PLP affinity chromatography, OSR pollen profilin was
      purified as a single protein of 14.5 kD and further identified as a profilin by
      three polyclonal rabbit antisera raised against ragweed and tobacco pollen
      profilin and the C-terminus of birch profilin. IgE binding of a human serum pool
      (n = 15) and four profilin-reactive sera to nitrocellulose-blotted OSR profilin
      was completely inhibited by 1 microg/ml rBet v 2 (birch profilin). Reciprocal
      ELISA inhibition using increasing concentrations of rBet v 2 and purified OSR
      profilin, respectively, showed that rBet v 2 strongly inhibits antibody binding
      to OSR profilin, whereas almost 100 times the amount of OSR profilin was needed
      to inhibit IgE binding to rBet v 2. Skin prick tests were positive (wheal >/=3
      mm) with 5 microg/ml rBet v 2 in all three patients tested, and with OSR profilin
      in two patients at a concentration of 50 microg/ml. CONCLUSIONS: OSR pollen
      profilin shares IgE and IgG epitopes with Bet v 2 and other plant profilins and
      may represent a potentially relevant allergen for profilin-sensitized patients.

PMID- 14600426
TI  - Cytokine synthesis in occupational allergy to caddisflies in hydroelectric plant
      workers.
AB  - BACKGROUND: Workers in hydroelectric plants appear to be readily sensitized to
      caddisfly allergens. This sensitization probably occurs de novo from occupational
      exposure. In some workers, sensitization occurs on a non-atopic background.
      Cytokine synthesis of IFN-gamma, IL-5 and IL-13 in atopic and non-atopic
      caddisfly-allergic workers was examined to determine if responses were similar or
      different. METHODS: Peripheral blood mononuclear cells were isolated from atopic
      caddisfly-allergic workers, non-atopic caddisfly-allergic workers and non-atopic
      caddisfly-exposed but non-allergic workers. Stimulation with caddisfly antigens
      was carried out and synthesis of IFN-gamma, IL-5 and IL-13 was determined by
      sandwich ELISA. RESULTS: Both caddisfly-allergic and non-allergic subjects
      responded to stimulation with caddisfly extract. The response in non-atopic
      caddisfly-non-allergic subjects was TH1 predominant, while that in atopic
      caddisfly-allergic subjects was TH2 predominant. The response in non-atopic
      caddisfly-allergic subjects was between that of the atopic caddisfly-allergic
      workers and the non-atopic caddisfly-non-allergic workers and the trend was to a
      TH2 response. Work-related symptoms were similarly intermediate between the
      atopic caddisfly-allergic and non-atopic caddisfly-non-allergic group.
      Differences were significant for IFN-gamma/IL-5 ratios but not IFN-gamma/IL-13
      ratios for atopic and non-atopic caddisfly-allergic individuals, compared to non
      atopic caddisfly-non-allergic workers. However, a linear relationship existed
      between IFN-gamma synthesis and IL-5 and IL-13 synthesis in non-atopic caddisfly
      allergic workers but not in atopic caddisfly-allergic subjects. CONCLUSIONS:
      Caddisfly allergy in hydroelectric workers may be a useful model for the
      development of allergy to a previously unencountered allergen, and points to some
      interesting differences between atopic and non-atopic subjects who become
      sensitized to environmental allergens.

PMID- 14600425
TI  - How accurate and safe is the diagnosis of hazelnut allergy by means of commercial
      skin prick test reagents?
AB  - BACKGROUND: Allergy to tree nuts, like hazelnuts, ranks among the most frequently
      observed food allergies. These allergies can start at early childhood and are, in
      contrast to other food allergies, not always outgrown by the patient. Tree nut
      allergy is frequently associated with severe reactions. Diagnosis partially
      relies on in vivo testing by means of a skin prick test (SPT) using commercially
      available SPT reagents. METHODS: Protein and allergen composition of nine
      commercial SPT solutions was evaluated using standard protein detection methods
      and specific immunoassays for measurement of five individual allergens.
      Diagnostic performance was assessed by SPT in 30 hazelnut-allergic subjects, of
      which 15 were provocation proven. RESULTS: Protein concentrations ranged from 0.2
      14 mg/ml. SDS-PAGE/silver staining revealed clear differences in protein
      composition. The major allergen Cor a 1 was present in all extracts but
      concentrations differed up to a factor 50. An allergen associated with severe
      symptoms, Cor a 8 (lipid transfer protein), was not detected on immunoblot in
      three products, and concentrations varied by more than a factor 100 as was shown
      by RAST inhibition. Similar observations were made for profilin, thaumatin-like
      protein and a not fully characterized 38-kD allergen. Ratios of individual
      allergens were variable among the nine extracts. SPT showed significant
      difference, and 6/30 patients displayed false-negative results using 3/9
      products. CONCLUSION: Variability in the composition of products for the
      diagnosis of hazelnut allergy is extreme. Sometimes, allergens implicated in
      severe anaphylaxis are not detected by immunoblotting. These shortcomings in
      standardisation and quality control can potentially cause a false-negative
      diagnosis in subjects at risk of severe reactions to hazelnuts.

PMID- 14600427
TI  - The interleukin-13 production by peripheral blood T cells from atopic dermatitis
      patients does not require CD2 costimulation.
AB  - BACKGROUND: Although allergic mechanisms appear to be important, the pathogenesis
      of both extrinsic and intrinsic forms of atopic dermatitis (AD) is unknown.
      METHODS: We compared the cytokine production of peripheral blood mononuclear
      cells of extrinsic AD (EAD) and intrinsic AD (IAD) patients and normal control
      individuals after stimulation with anti-CD3 and/or anti-CD28 monoclonal
      antibodies (mAbs) in the presence or absence of anti-CD2-blocking mAb. The
      cytokine production was measured by immunoassays in supernatants of 24-hour
      cultures. RESULTS: EAD patients showed a decreased capacity to synthesize
      interferon gamma and granulocyte-macrophage colony-stimulating factor upon anti
      CD3 mAb stimulation as compared with IAD patients. Both EAD and IAD patients
      demonstrated an increased production of interleukin (IL)-5 and IL-13. As
      expected, interferon gamma, granulocyte-macrophage colony-stimulating factor, and
      IL-5 levels were reduced in the presence of anti-CD2-blocking mAbs. CD28
      costimulation restored the release in cultures with anti-CD2 mAbs added,
      suggesting that CD2 and CD28 have redundant functions in T cell activation and
      subsequent cytokine production. Strikingly, the IL-13 production was not blocked
      by anti-CD2 mAbs and also not increased by agonistic anti-CD28 mAb, in particular
      within the EAD patient group. CONCLUSION: The signalling pathway initiated by the
      T cell receptor complex leading to increased IL-13 production in AD patients
      appears to be highly sensitive and is largely independent on CD2 costimulatory
      signals.

PMID- 14600428
TI  - Analysis of highly expressed genes in monocytes from atopic dermatitis patients.
AB  - BACKGROUND: Monocytes, macrophages, and antigen-presenting cells (APCs) are key
      effectors of both innate and acquired immune responses. Such cells have been
      implicated in the pathogenesis of some inflammatory diseases. Differential gene
      expression in CD14-positive cells from patients with atomic dermatitis (AD) was
      studied using real-time quantitative RT-PCR to measure transcription levels of
      selected genes. METHODS: PBMCs were prepared by Ficoll gradient separation from
      30 AD patients (the anti-mite-specific IgE RAST score: 0.75 to >100 UA/ml) and 10
      healthy adult individuals (the RAST score: <0.34-0.37 UA/ml) and CD14-positive
      cells were selected. A total of 64 genes was selected for study from groups of
      genes with different molecular function. RESULTS: Genes involved in MHC class I
      antigen presentation, such as beta(2)-microglobulin, subunits of an
      immunoproteasome and ATP-binding cassette transporter TAP2 were expressed at
      higher levels in the AD patients than in the healthy controls. The genes for Toll
      like receptors, CD36 and IFNgamma receptor were also upregulated in the AD
      patients. These genes are involved in MHC class I antigen presentation,
      recognition of bacterial pathogens and apoptotic cells. CONCLUSIONS: The
      upregulation of genes suggests that circulating monocytes in AD patients may be
      primed to differentiate into effector cells by conditions associated with AD. The
      upregulation of genes may prove to be a useful marker for AD.

PMID- 14600429
TI  - Potential action of IL-4 and IL-13 as fibrogenic factors on lung fibroblasts in
      vitro.
AB  - BACKGROUND: Asthma is characterized by chronic inflammation of the airway with
      the presence of Th2 cytokines. Airway remodeling in asthma is closely related to
      clinical manifestations. Lung myofibroblasts play a critical role in the airway
      remodeling and Th2 cytokines may modulate their behavior. We examined the effect
      of two major Th2 cytokines, IL-4 and IL-13, on differentiation of lung
      fibroblasts to myofibroblasts. We hypothesized that these cytokines would
      stimulate fibroblast proliferation in association with decreased prostaglandin
      E(2) (PGE(2)). METHODS: Lung fibroblasts were incubated with IL-4 and IL-13 with
      or without Th1 cytokine interferon-gamma (IFN-gamma) in vitro. Differentiation of
      lung fibroblasts to myofibroblasts was characterized by the expression of alpha
      smooth muscle actin (alpha-SMA) as well as a morphological and
      immunohistochemical analysis. Fibroblast proliferation stimulated by IL-4 and IL
      13 was assessed with the MTT assay. We also investigated the effect of these
      cytokines on cyclooxygenase (COX) gene expression and PGE(2) production. RESULTS:
      IL-4 and IL-13 increased alpha-SMA expression and myofibroblastic
      differentiation. This effect was attenuated by IFN-gamma and dexamethasone failed
      to have an influence on differentiation. IL-4 and IL-13 stimulated fibroblast
      proliferation. These cytokines downregulated the expression of both COX-1 and COX
      2 genes and decreased the production of PGE(2). CONCLUSIONS: IL-4 and IL-13
      induce differentiation of fibroblasts to myofibroblasts and this response is
      attenuated by IFN-gamma. IL-4 and IL-13 stimulate fibroblast proliferation and
      this effect is at least partly due to suppressed COX gene expressions and
      subsequently decreased PGE(2) production. These findings suggest that IL-4 and IL
      13 directly act on lung fibroblast to induce a fibrogenic response.

PMID- 14600430
TI  - Correlation between T-cell and mast cell activity in patients with chronic
      urticaria.
AB  - BACKGROUND: The presence of autoantibodies reacting with the high affinity IgE
      receptor (FcepsilonRIalpha) usually indicates a more severe form of chronic
      urticaria (CU). Previously, we showed an increased lymphocyte reactivity in CU
      patients; however, the relation between enhanced cellular immunity and the
      presence of anti-FcepsilonRIalpha-specific autoantibodies has not been
      investigated. METHODS: Cellular and humoral immune reactivity of 50 CU patients
      and 28 healthy controls was studied. Serum sIL-2R, neopterin, and tryptase levels
      were measured to assess T-cell, monocyte/macrophage and mast cell activity,
      respectively. Helicobacter pylori (HP)-specific IgG antibody, and IgE levels were
      also tested. Anti-FcepsilonRIalpha-specific autoantibody was determined by
      Western blotting. In vivo histamine-releasing activity of patients' sera was
      assessed by the autologous serum skin test (AST). RESULTS: 17/50 CU patients, who
      both had IgG-type anti-FcepsilonRIalpha-antibodies by Western blotting and a
      positive AST response, were classified as autoimmune CU. All patients with CU had
      significantly higher serum sIL-2R and tryptase levels than healthy controls (p =
      0.000257, p = 0.000166, respectively), indicating T-cell and mast cell
      activation. Patients with higher sIL-2R levels also had higher tryptase levels;
      the strongest correlation was shown in the autoimmune subgroup of patients (rho =
      0.688, p = 0.002). There was a tendency towards higher tryptase levels in the
      autoimmune subgroup, as compared to the nonautoimmune CU patients. While the
      serum IgE was significantly lower in autoimmune than in nonautoimmune CU (p =
      0.000836), there was no significant difference in their sIL-2R, neopterin and HP
      specific IgG antibody levels. CU patients with a positive AST response (38/50)
      had significantly higher tryptase levels (p = 0.0107) when compared to the
      negative skin test group. CONCLUSIONS: The significant correlation between sIL-2R
      and tryptase levels in patients with CU indicates that T cell activation is
      proportional to mast cell degranulation in these patients. The increased level of
      tryptase in autoimmune CU may suggest more severe disease.

PMID- 14600431
TI  - No effect of angiotensin-converting enzyme gene polymorphism on disease
      progression and left ventricular hypertrophy in autosomal dominant polycystic
      kidney disease.
AB  - BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) shows a variable
      clinical course suggesting that genetic modifiers might play a role. There are
      conflicting results about the effect of angiotensin-converting enzyme (ACE) gene
      polymorphism on the progression of renal failure in ADPKD. Also, the association
      between ACE gene polymorphism and the occurrence of left ventricular hypertrophy
      (LVH) has not been investigated in patients with ADPKD. METHODS: ACE genotype
      analysis was performed in 409 Caucasian patients (137 male, 272 female) with
      ADPKD. Echocardiographic examination was done in 164 of these patients. RESULTS:
      There were no significant differences between different ACE genotypes regarding
      renal function, renal volume, urinary protein excretion, blood pressure, the rate
      of hypertension, the age at diagnosis of hypertension, the rate of LVH and the
      incidence of end-stage renal disease (ESRD). CONCLUSION: ACE gene polymorphism
      does not have a significant effect on the development of ESRD and the prevalence
      of LVH in patients with ADPKD.

PMID- 14600432
TI  - Translational paradigms in cerebrovascular gene transfer.
AB  - Gene transfer involves the use of an engineered biologic vehicle known as a
      vector to introduce a gene encoding a protein of interest into a particular
      tissue. In diseases with known defects at a genetic level, gene transfer offers a
      potential means of restoring a normal molecular environment via vector-mediated
      entry (transduction) and expression of genes encoding potentially therapeutic
      proteins selectively in diseased tissues. The technology of gene transfer
      therefore underlies the concept of gene therapy and falls under the umbrella of
      the current genomics revolution. Particularly since 1995, numerous attempts have
      been made to introduce genes into intracranial blood vessels to demonstrate and
      characterize viable transduction. More recently, in attempting to translate
      cerebrovascular gene transfer technology closer to the clinical arena, successful
      transductions of normal human cerebral arteries ex vivo and diseased animal
      cerebral arteries in vivo have been reported using vasomodulatory vectors.
      Considering the emerging importance of gene-based strategies for the treatment of
      the spectrum of human disease, the goals of the present report are to overview
      the fundamentals of gene transfer and review experimental studies germane to the
      clinical translation of a technology that can facilitate genetic modification of
      cerebral blood vessels.

PMID- 14600433
TI  - Energy substrates for neurons during neural activity: a critical review of the
      astrocyte-neuron lactate shuttle hypothesis.
AB  - Glucose had long been thought to fuel oxidative metabolism in active neurons
      until the recently proposed astrocyte-neuron lactate shuttle hypothesis (ANLSH)
      challenged this view. According to the ANLSH, activity-induced uptake of glucose
      takes place predominantly in astrocytes, which metabolize glucose anaerobically.
      Lactate produced from anaerobic glycolysis in astrocytes is then released from
      astrocytes and provides the primary metabolic fuel for neurons. The conventional
      hypothesis asserts that glucose is the primary substrate for both neurons and
      astrocytes during neural activity and that lactate produced during activity is
      removed mainly after neural activity. The conventional hypothesis does not assign
      any particular fraction of glucose metabolism to the aerobic or anaerobic
      pathways. In this review, the authors discuss the theoretical background and
      critically review the experimental evidence regarding these two hypotheses. The
      authors conclude that the experimental evidence for the ANLSH is weak, and that
      existing evidence and theoretical considerations support the conventional
      hypothesis.

PMID- 14600434
TI  - Food for thought: challenging the dogmas.

PMID- 14600435
TI  - Putative cyclooxygenase-3 expression in rat brain cells.
AB  - Cyclooxygenase-3 (COX-3), a new acetaminophen-sensitive isoform of the COX
      family, has recently been cloned from canine tissues. Canine COX-3 apparently is
      identical to the full-length form of COX-1, with the exception that the COX-3
      mRNA retains intron 1. Additionally, COX-3 mRNA expression is high in the brain.
      We investigated the expression of the putative rat COX-3 mRNA in primary cultures
      of neurons, astrocytes, endothelial cells, pericytes, and choroidal epithelial
      cells from the rat brain. Specific RT-PCR primers were designed to detect
      putative rat COX-3 mRNA, and the RT-PCR products were sequenced and compared to
      the known sequence of the rat COX-1 gene. Our results demonstrate that the mRNA
      of the putative COX-3 is expressed in all of the cell types except neurons.
      Cerebral endothelial cells showed the highest COX-3 expression. Whereas COX-2
      expression increased several-fold after lipopolysaccharide (LPS) challenge, COX-1
      and COX-3 expression did not change significantly, suggesting that cells
      constitutively express COX-3. In summary, we report, for the first time to our
      knowledge, that the putative COX-3 mRNA is detectable in rats and is
      differentially expressed in various cell types from rat brain, as well as that
      its expression is not stimulated by LPS.

PMID- 14600436
TI  - Microvascular Basal lamina damage after embolic stroke in the rat: relationship
      to cerebral blood flow.
AB  - Microvascular basal lamina damage has been demonstrated after balloon occlusion
      of the middle cerebral artery in the nonhuman primate and after intravascular
      filament occlusion in the rat. The aim of the present study was to investigate in
      the rat whether microvascular damage can be found in the stroke model of
      intracarotid clot injection as early as 3 hours after clot injection and whether
      microvascular damage relates to the level of regional cerebral blood flow (rCBF).
      Microvascular densities and total stained microvascular areas were determined by
      immunohistochemistry of collagen type IV in cortex and basal ganglia and
      automatic video-imaging analysis. rCBF was measured by autoradiography in the
      same brain areas. Compared with the corresponding areas in the nonischemic
      hemisphere, a significant loss of microvascular density (-16%) and total stained
      microvascular areas (-10%) was observed in these areas. The reduction of
      microvascular basal lamina staining was comparable in all animals and was not
      related to the value of rCBF when measured 3 hours after onset of embolic stroke.
      In conclusion, microvascular damage occurs as soon as 3 hours after intracarotid
      clot injection, even in brain areas in which rCBF has returned to normal values.

PMID- 14600437
TI  - Lactate is a preferential oxidative energy substrate over glucose for neurons in
      culture.
AB  - The authors investigated concomitant lactate and glucose metabolism in primary
      neuronal cultures using 13C- and 1H-NMR spectroscopy. Neurons were incubated in a
      medium containing either [1-13C]glucose and different unlabeled lactate
      concentrations, or unlabeled glucose and different [3-13C]lactate concentrations.
      Overall, 13C-NMR spectra of cellular extracts showed that more 13C was
      incorporated into glutamate when lactate was the enriched substrate. Glutamate
      13C-enrichment was also found to be much higher in lactate-labeled than in
      glucose-labeled conditions. When glucose and lactate concentrations were
      identical (5.5 mmol/L), relative contributions of glucose and lactate to neuronal
      oxidative metabolism amounted to 21% and 79%, respectively. Results clearly
      indicate that when neurons are in the presence of both glucose and lactate, they
      preferentially use lactate as their main oxidative substrate.

PMID- 14600439
TI  - A theoretical model of oxygen delivery and metabolism for physiologic
      interpretation of quantitative cerebral blood flow and metabolic rate of oxygen.
AB  - The coupling of cerebral blood flow (CBF) and metabolic rate of oxygen (CMRO2)
      during physiologic and pathophysiologic conditions remains the subject of debate.
      In the present study, we have developed a theoretical model for oxygen delivery
      and metabolism, which describes the diffusion of oxygen at the capillary-tissue
      interface and the nonlinear nature of hemoglobin (Hb) affinity to oxygen,
      allowing a variation in simple-capillary oxygen diffusibility, termed "effective
      oxygen diffusibility (EOD)." The model was used to simulate the relationship
      between CBF and CMRO2, as well as oxygen extraction fraction (OEF), when various
      pathophysiologic conditions were assumed involving functional activation,
      ischemia, hypoxia, anemia, or hypo- and hyper-capnic CBF variations. The
      simulations revealed that, to maintain CMRO2 constant, a variation in CBF and Hb
      required active change in EOD. In contrast, unless the EOD change took place, the
      brain allowed small but significant nonlinear change in CMRO2 directly dependent
      upon oxygen delivery. Application of the present model to quantitative
      neuroimaging of CBF and CMRO2 enables us to evaluate the biologic response at
      capillary level other than Hb- and flow-dependent properties of oxygen transport
      and may give us another insight regarding the physiologic control of oxygen
      delivery in the human brain.

PMID- 14600438
TI  - Advanced glycation endproducts induce changes in glucose consumption, lactate
      production, and ATP levels in SH-SY5Y neuroblastoma cells by a redox-sensitive
      mechanism.
AB  - Advanced glycation endproducts (AGEs) accumulate on long-lived proteins,
      including beta-amyloid plaques in Alzheimer's disease, and are suggested to
      contribute to neuronal dysfunction and cell death. We have investigated the
      effects of a model AGE upon glucose metabolism and energy production in a
      neuroblastoma cell line. AGEs decrease cellular ATP levels and increase glucose
      consumption and lactate production. All of the AGE-induced metabolic changes can
      be attenuated by antioxidants such as (R+)-alpha-lipoic acid and 17beta
      estradiol. These antioxidants may become useful drugs against (AGE-mediated)
      effects in neurodegeneration through their positive effects on cellular energy
      metabolism.

PMID- 14600440
TI  - Inducible repair of oxidative DNA lesions in the rat brain after transient focal
      ischemia and reperfusion.
AB  - To determine the role of oxidative DNA damage and repair in brain injury after
      focal ischemia and reperfusion, the authors investigated DNA base damage and DNA
      base excision repair (BER) capacity, the predominant repair mechanism for
      oxidative DNA lesions, in the rat model of temporary middle cerebral artery
      occlusion. Contents of 8-hydroxyl-2'-deoxyguanosine (8-oxodG) and
      apurinic/apyrimidinic abasic site (AP site), hallmarks of oxidative DNA damage,
      were quantitatively measured in nuclear DNA extracts from brains 0.25 to 72 hours
      after 1 hour of middle cerebral artery occlusion. In parallel to the detection of
      DNA lesions, the capacity for 8-oxodG- or AP site-dependent DNA repair synthesis
      was measured in nuclear protein extracts using specific in vitro DNA repair
      assays. After postischemic reperfusion, the levels of 8-oxodG and AP sites were
      markedly increased in ischemic tissues. In frontal/parietal cortex, regions that
      survived ischemia, 8-oxodG and AP sites were efficiently repaired during
      reperfusion. However, in the caudate, a region that was destined to infarct, the
      DNA lesions were poorly repaired. In consistent with the patterns of endogenous
      lesion repair, a markedly induced and long-lasting (at least 72 hours) BER
      activity was detected in the cortex but not in the caudate after ischemia. The
      induced BER activity in ischemic cortex was attributed to the upregulation of
      gene expression and activation of selective BER enzymes, particularly DNA
      polymerase-beta and OGG1. These results strongly suggest that inducible DNA BER
      constitutes an important endogenous mechanism that protects brain against
      ischemia-induced oxidative neuronal injury.

PMID- 14600441
TI  - Axon function persists during anoxia in mammalian white matter.
AB  - Axon function in the CNS has been reported to fail rapidly during anoxia,
      implying that there is no anaerobic capacity. This phenomenon was reassessed in
      rodent white matter using mouse or rat optic nerve. Axon function was
      semiquantitatively measured as area under the compound action potential. Mouse
      optic nerves exposed to anoxia (30-180 minutes) or cyanide (30-60 minutes) at 37
      degrees C exhibited significant persistent function that was abolished by
      removing glucose. Reduction in compound action potential area increased with
      anoxia duration reaching a maximum of about 70% after 90 min. Rat optic nerves
      exposed to anoxia, in contrast to mouse optic nerves, showed rapid and complete
      loss of function. When artificial CSF glucose was increased from 10 to 30 mmol/L,
      rat optic nerves responded to anoxia in a similar manner to mouse optic nerves in
      10-mmol/L glucose. The authors conclude that white matter is resistant to anoxia
      with a subset of axons able to subsist exclusively on anaerobically derived
      energy. Because the rat optic nerve is about twice the diameter of the mouse
      optic nerve, glucose diffusion into the rat optic nerve was inadequate during
      anoxia when artificial CSF glucose was 10 mmol/L but became adequate when
      artificial CSF glucose was 30 mmol/L. These observations have implications for
      white matter energy metabolism and susceptibility to injury during focal
      ischemia.

PMID- 14600443
TI  - In vivo monitoring of macrophage infiltration in experimental ischemic brain
      lesions by magnetic resonance imaging.
AB  - Although macrophages represent the major inflammatory cells in cerebral ischemia,
      the kinetics of macrophage infiltration are largely unknown. To address this
      issue, we injected superparamagnetic iron oxide (SPIO) particles into the
      circulation of rats at different time points after focal photothrombotic cerebral
      infarction and performed magnetic resonance imaging (MRI) 24 hours later.
      Infarcts appeared as hyperintense lesions on T2-w and CISS MR images during all
      stages. At days 5.5 and 6, an additional rim of signal loss indicative of local
      accumulation of SPIO particles appeared at the outer margin of the hyperintense
      ischemic lesions, which was not present at days 1 to 5. Areas of signal loss
      corresponded to local accumulation of iron-loaded macrophages in histologic
      sections. At day 8, signal loss became restricted to the inner core of the
      lesions and ceased thereafter. Macrophages, however, were still present in late
      ischemic brain lesions, but they were iron-negative. Thus SPIO-induced signal
      loss indicates active macrophage transmigration into ischemic infarcts but not
      their mere presence. SPIO-induced signal loss was independent from the
      disturbance of the blood-brain barrier. In conclusion, we have shown by in vivo
      monitoring that macrophages enter photothrombotic infarcts at late stages of
      infarct development, suggesting a role in tissue remodeling rather than neuronal
      injury.

PMID- 14600442
TI  - The protective effects of preconditioning on cerebral endothelial cells in vitro.
AB  - Ischemic preconditioning (PC) can markedly reduce ensuing ischemic damage.
      Although most attention has focused on the neuronal effects of PC, the authors
      have recently shown that ischemic PC reduces ischemia-induced cerebrovascular
      damage. In vivo, it is difficult to ascertain whether this is a direct
      cerebrovascular effect of PC. This study, therefore, examined whether cerebral
      endothelial cells can be preconditioned in vitro in the absence of other cell
      types. Experiments were performed on an immortalized mouse brain endothelial cell
      line or primary cultures of mouse brain microvessel endothelial cells. Cells were
      exposed to oxygen glucose deprivation (OGD) of either short duration, as a PC
      stimulus, or a long duration (5 hours) with or without reoxygenation to induce
      endothelial damage. Endothelial injury was assessed by measuring lactate
      dehydrogenase release and the expression of intercellular adhesion molecule-1 at
      the protein and mRNA levels. Experiments indicated that 1 hour of OGD was the
      optimal PC stimuli and that a 1 or 3 day interval was the optimal time interval
      between the PC stimulus and the injurious event. Preconditioned cells had less
      lactate dehydrogenase release during OGD (+/- reoxygenation) and reduced
      intercellular adhesion molecule-1 expression after OGD with reoxygenation. This
      study shows that cerebral endothelial cells can be directly preconditioned. The
      importance of this phenomenon in the overall effects of PC on the brain remains
      to be elucidated. Understanding the protective mechanisms elicited by PC may give
      insight into how to prevent ischemia-induced vascular damage (e.g., hemorrhagic
      transformation).

PMID- 14600444
TI  - Hypointense transcerebral veins at T2*-weighted MRI: a marker of hemorrhagic
      transformation risk in patients treated with intravenous tissue plasminogen
      activator.
AB  - Prediction of hemorrhagic transformation (HT) in patients treated by intravenous
      recombinant tissue-type plasminogen activator (rt-PA) is a challenging issue in
      acute stroke management. HT may be correlated with severe hypoperfusion. Signal
      changes may be observed at susceptibility-weighted magnetic resonance imaging
      (MRI) within large perfusion defects. A signal drop within cerebral veins at T2*
      weighted gradient-echo MRI may be expected in severe ischemia, and may indicate
      subsequent risk of HT. The authors prospectively searched for an abnormal
      visibility of transcerebral veins (AVV) within the ischemic area in patients with
      hemispheric ischemic stroke, before they were treated with intravenous rt-PA
      therapy. Any correlation between AVV and baseline clinical or MRI findings, or
      further HT, was noted. An AVV was present in 23 of 49 patients (obvious, n = 8;
      moderate, n = 15), and was supported by severe hemodynamic changes at baseline
      MRI. The AVV was correlated with the occurrence of parenchymal hematoma type 2 at
      computed tomography during the first week (r = 0.44, P = 0.002). Five of six type
      2 parenchymal hematomas occurred in association with obvious AVV. At multiple
      regression analysis, two baseline MRI factors had an independent predictive value
      for HT risk during the first week: the AVV and the cerebral blood volume ratio
      (Nagelkerke R2 = 0.48).

PMID- 14600445
TI  - Responses of posttraumatic pericontusional cerebral blood flow and blood volume
      to an increase in cerebral perfusion pressure.
AB  - In and around traumatic contusions, cerebral blood flow (CBF) is often near or
      below the threshold for ischemia. Increasing cerebral perfusion pressure (CPP) in
      patients with head injuries may improve CBF in these regions. However, the
      pericontusional response to this intervention has not been studied. Using
      positron emission tomography (PET), we have quantified the response to an
      increase in CPP in and around contusions in 18 contusions in 18 patients.
      Regional CBF and cerebral blood volume (CBV) were measured with PET at CPPs of 70
      and 90 mmHg using norepinephrine to control CPP. Based upon computed tomography,
      regions of interest (ROIs) were placed as two concentric ellipsoids, each of 1-cm
      width, around the core of the contusions. Measurements were compared with a
      control ROI in tissue with normal anatomic appearance. Baseline CBF and CBV
      increased significantly with increasing distance from the core of the lesion. The
      increase in CPP led to small increases in CBF in all ROIs except the core. The
      largest absolute CBF increase was found in the control ROI. Relative CBF
      increases did not differ between ROIs so that ischemic areas remained ischemic.
      Pericontusional oedema on computed tomography was associated with lower absolute
      values of CBF and CBV but did not differ from nonoedematous tissue in the
      relative response to CPP elevation.

PMID- 14600446
TI  - Cerebral and cerebellar activation in power and precision grip movements: an H2
      15O positron emission tomography study.
AB  - SUMMARY: Most human manual grip movements can be divided into power gripping and
      precision gripping, but central neural control during these tasks remains
      unclear. We investigated activation of the whole brain to analyze how simple hand
      movements are performed. The cerebral blood flow of seven healthy right-handed
      volunteers was measured by H2 15O positron emission tomography during right grip
      tasks without gripping a target object. Auditory-cued, repetitive power grips
      (i.e., fist making) and repetitive precision grips (i.e., opposition of the tip
      of the index finger and the tip of the thumb) were performed at 1.26 Hz. The
      areas activated during both tasks were the left primary sensorimotor cortex,
      caudal portion of the dorsal premotor, caudal portion of the supplementary motor
      area, cingulate motor area, and the right spinocerebellum and intermediate region
      of the cerebrocerebellum in comparison with the rest state. The analysis of power
      grip-precision grip tasks showed the activated peaks in the upper portion of the
      left sensorimotor area and right cerebellar vermis, but these areas were
      activated in both the tasks [(power grip-rest) and (precision grip-rest)] with
      uncorrected P < 0.001 as the statistical criterion. With P < 0.05 corrected as
      the statistical criterion, the results showed no significant activated peaks in
      regional cerebral blood flow. Our findings indicate no difference in brain
      activation between the acts of power grip and precision grip without a target
      object.

PMID- 14600447
TI  - Magnetic resonance: an introduction to ultrashort TE (UTE) imaging.
AB  - The background underpinning the clinical use of ultrashort echo-time (UTE) pulse
      sequences for imaging tissues or tissue components with short T2s is reviewed.
      Tissues properties are discussed, and tissues are divided into those with a
      majority of short T2 relaxation components and those with a minority. Features of
      the basic physics relevant to UTE imaging are described including the fact that
      when the radiofrequency pulse duration is of the order T2, rotation of tissue
      magnetization into the transverse plane is incomplete. Consequences of the broad
      line-width of short T2 components are also discussed including their partial
      saturation by off-resonance fat suppression pulses as well as multislice and
      multiecho imaging. The need for rapid data acquisition of the order T2 is
      explained. The basic UTE pulse sequence with its half excitation pulse and radial
      imaging from the center of k-space is described together with options that
      suppress fat and/or long T2 components. Image interpretation is discussed.
      Clinical features of the imaging of cortical bone, tendons, ligaments, menisci,
      and periosteum as well as brain, liver, and spine are illustrated. Short T2
      components in all of these tissues may show high signals. Possible future
      developments are outlined as are technical limitations.

PMID- 14600448
TI  - Abdominal multidetector row computed tomography: reduction of cost and contrast
      material dose using saline flush.
AB  - OBJECTIVE: To evaluate the potential of a saline solution flush after the
      contrast material bolus in abdominal multidetector row CT (MDCT) in contrast
      material dose and cost reduction. METHODS: Abdominal MDCT was performed in 78
      patients who were assigned randomly to 2 groups receiving 120 mL nonionic
      contrast material (300 mgI/mL) alone or 100 mL of the same contrast material
      pushed with 40 mL of saline solution. Mean attenuation values for both groups
      were measured in the liver, the spleen, the pancreas, the portal vein, the
      inferior vena cava, and the abdominal aorta. Cost analyses were performed for
      both groups. RESULTS: There was no significant difference in parenchymal and
      vascular enhancement between both groups. The difference of the enhancement was 2
      HU for the liver (P = 0.11), 2 HU for the spleen (P = 0.44), 3 HU for the
      pancreas (P = 0.38), 9 HU for the portal vein (P = 0.11), 3 HU for the inferior
      vena cava (P = 0.55), and 10 HU for the aorta (P = 0.06). Taking the costs of
      contrast material, saline solution, and disposal material into account, 7.30
      dollars was saved by the patient using a saline solution flush. CONCLUSIONS:
      Using a saline flush after the contrast material bolus in abdominal MDCT allows
      an iodine dose reduction of approximately 6 g, or 17%, without impairing mean
      parenchymal and vascular enhancement and a cost reduction of 7.30 dollars per
      patient.

PMID- 14600449
TI  - Temporal peritumoral enhancement of hepatic cavernous hemangioma: findings at
      multiphase dynamic magnetic resonance imaging.
AB  - OBJECTIVE: To evaluate the occurrence rate of temporal peritumoral enhancement
      associated with hepatic cavernous hemangiomas and to correlate that with the
      speed of intratumoral contrast enhancement and tumor volume. METHODS: Dynamic
      magnetic resonance imaging (MRI) of 69 consecutive patients with 136 hemangiomas
      was reviewed for peritumoral enhancement. Tumor volume was estimated by the
      largest diameter on T2-weighted images. Speed of intratumoral contrast
      enhancement was determined by portal phase image and was categorized as rapid
      (>75% of tumor volume), intermediate (25%-75% of tumor volume), or slow (<25% of
      tumor volume). RESULTS: Temporal peritumoral enhancement was found in 37 (26.6%)
      of 136 hemangiomas. It was more common in hemangiomas with rapid enhancement (30
      of 67 cases [44.8%]) than in those with intermediate (3 of 22 cases [13.6%]) and
      slow (4 of 47 cases [8.5%]) enhancement (P < 0.05). There was no statistically
      significant relation between lesion size and presence of temporal peritumoral
      enhancement (P > 0.05). CONCLUSIONS: Temporal peritumoral enhancement is not
      uncommonly seen in hepatic cavernous hemangiomas at dynamic MRI. It is most
      commonly encountered in rapidly enhancing small lesions. There is no
      statistically significant relation between temporal peritumoral enhancement and
      tumor volume, however.

PMID- 14600450
TI  - Appearance and distinguishing features of retroperitoneal calcifications at
      computed tomography.
AB  - OBJECTIVES: To describe the appearance of retroperitoneal calcifications seen at
      computed tomography (CT) and to investigate which CT features distinguish benign
      from malignant retroperitoneal calcifications. METHODS: We identified 25 patients
      with retroperitoneal calcifications by retrospective review of 39,931
      abdominopelvic CT scans. Etiology of retroperitoneal calcifications was
      determined by examination of medical and histopathological records. By consensus,
      2 abdominal radiologists recorded calcification number (solitary or multiple),
      location (suprarenal or infrarenal), morphology (globular or nonglobular), and
      the presence of soft-tissue components. The association between CT findings and
      etiology was assessed using the Fisher exact test. RESULTS: Retroperitoneal
      calcifications were malignant in 15 patients and benign in 10. Solitary
      calcifications were seen more commonly in patients with benign disease (6 of 10
      vs. 1 of 15, P < 0.01). Suprarenal calcifications were seen only in patients with
      malignancy (13 of 15 patients, P < 0.01). Nonglobular calcifications were seen
      only in patients with benign disease (6 of 10, P < 0.01). Soft-tissue components
      were seen more commonly in patients with malignancy (14 of 15 vs. 4 of 10; P <
      0.01). CONCLUSIONS: Retroperitoneal calcifications are rarely seen at CT and may
      be benign or malignant in etiology. Solitary or nonglobular retroperitoneal
      calcifications are likely to be benign while calcifications that are multiple,
      globular, suprarenal, or associated with noncalcified soft-tissue components are
      likely to be malignant.

PMID- 14600451
TI  - Comparison of spatial resolution in high-resolution multislice computed
      tomography and digital subtraction angiography using renal specimens.
AB  - OBJECTIVE: To compare maximum spatial resolution in multislice computed
      tomography (MS-CT) and digital subtraction angiography (DSA) using an arterial
      tree model for canine kidney specimens. METHODS: Twenty-three isolated fox
      terrier kidneys were catheterized with a 4F catheter and underwent contrast
      enhanced MS-CT with a maximum spatial resolution of 0.23-mm isotropic voxel size
      in an early arterial phase. In addition, a digital subtraction angiogram was
      performed on all kidneys. The kidneys were segmented semiautomatically, and each
      parenchymal vessel that was identified in the kidney was marked. The maximum
      intensity projections of arterial vessels in the CT datasets were evaluated in a
      comparison with the DSA datasets. RESULTS: No significant difference in vessel
      delineation and count was found at any level up to the fourth level of intrarenal
      branching. CONCLUSION: MS-CT has the potential of replacing DSA in the diagnosis
      of intrarenal arteries.

PMID- 14600452
TI  - Fatty metastatic lesions in 2 patients with renal clear-cell carcinoma.
AB  - This is a case report of 2 patients with previously resected renal cell carcinoma
      who present with unusual fatty lesions that proved to be metastases.

PMID- 14600453
TI  - Ovarian cystadenofibromas: characteristic magnetic resonance findings with
      pathologic correlation.
AB  - Ovarian cystadenofibroma is a benign tumor and may appear as a multilocular
      cystic mass with solid nodular components mimicking malignant ovarian tumor.
      Preoperative diagnosis is required to avoid excess surgical procedure. We report
      characteristic magnetic resonance imaging (MRI) findings of 2 cases with
      pathologic correlation. On T2-weighted images, the solid components of the tumors
      showed very low intensity, in which very high intense tiny cysts were present
      reflecting dense fibrous stromal proliferation with scattered small cystic
      glandular structures. This "black sponge"-like appearance was considered to be
      diagnostic.

PMID- 14600454
TI  - Cerebral blood flow index: dynamic perfusion MRI delivers a simple and good
      predictor for the outcome of acute-stage ischemic lesion.
AB  - OBJECTIVES: To evaluate the feasibility of utilizing cerebral blood flow (CBF)
      index images, calculated automatically and quickly from dynamic perfusion imaging
      (DPI), to identify acute cerebral ischemia. We attempted to investigate (1)
      whether the CBF index has a threshold for assessing tissue outcome, (2) whether
      CBF index images can predict the resulting infracted area, and if so, (3) whether
      the predictive capacity of the CBF index image is comparable to the regional CBF
      (rCBF) image delivered from singular value decomposition (SVD) deconvolution
      methods, which are regarded as most accurate in predicting the final infarct
      area. METHODS: Diffusion-weighted images (DWI) and DPI were obtained in 17
      patients within 12 hours of stroke onset and follow-up magnetic resonance imaging
      (MRI). On 3 DPI-delivered images, namely relative regional cerebral blood volume
      (rrCBV), uncorrected mean transit time (MTTu) and CBF index images, univariate
      discriminant analysis was done to estimate cut-off values to discriminate between
      infarcted and noninfarcted areas. Subsequently, correlations between the initial
      lesion volume of 3 images together with rCBF images delivered with SVD methods
      and the final infarct volume on follow-up T2-weighted MRI taken at the 8th to
      20th day were determined. RESULTS: Among the 3 images, only the CBF index image
      was able reveal the threshold of the ischemic region. Lesion volume of CBF index
      images against follow-up infarct volume had the highest correlation (r = 0.995)
      to a linear fit and the slope was closest to 1.0 (0.91) among the 3 and had
      identical accuracy to the regression coefficient of rCBF images. CONCLUSIONS: CBF
      index images can predict final infarct volume. Evaluating CBF index images
      together with DWI can guide the initial assessment in the acute stage of cerebral
      ischemia.

PMID- 14600455
TI  - Perfusion magnetic resonance imaging in intracerebral parenchymal tuberculosis:
      preliminary findings.
AB  - OBJECTIVES: To study the vascular perfusion patterns of focal intracerebral
      tubercular lesions using echoplanar magnetic resonance (MR) imaging-derived
      relative cerebral blood volume (rCBV) maps. METHODS: Seventeen focal tubercular
      lesions were evaluated with conventional and perfusion-weighted MR imaging on a
      1.5-T MR system. The rCBVs of the center, peripheral wall, and perilesional white
      matter were calculated from the perfusion MR-derived data. Perfusion MR imaging
      findings as depicted on the rCBV maps were qualitatively compared with those of
      conventional MR findings. RESULTS: Eleven of the 17 lesions demonstrated
      vascularity greater than that of the contralateral white matter on rCBV maps. The
      mean of the measured rCBV values of the peripheral wall and center of the lesions
      was 2.5 +/- 1.42 and 0.33 +/- 0.3 (mean +/- SD), respectively. Most of the
      hypervascular lesions (8) revealed a concentric peripheral wall having
      alternating hypointense and hyperintense signal intensity rims surrounding a
      variable intensity center on T2-weighted images. All the lesions having a nodular
      enhancing pattern (4) were hypervascular. CONCLUSIONS: Focal cerebral tubercular
      lesions can have variable vascularity as shown on perfusion MR-derived rCBV maps.
      It may be difficult to differentiate hypervascular lesions from cerebral tumors
      in some patients based on perfusion MR imaging alone.

PMID- 14600457
TI  - Computed tomography and magnetic resonance imaging findings of brain damage by
      hanging.
AB  - We reported computed tomography (CT) and magnetic resonance imaging (MRI)
      findings of brain damage of a 61-year-old man who attempted suicide by hanging.
      Unenhanced CT demonstrated multiple hyperdense areas indicating subcortical and
      subarachnoid hemorrhages and brain swelling. MRI demonstrated not only
      hemorrhagic findings, but also ischemic findings in the middle brain and cerebral
      cortex. Multifocal cerebral hemorrhages might be caused by venous hypertension
      due to compression of the jugular veins.

PMID- 14600456
TI  - Preoperative image fusion of fluoro-2-deoxy-D-glucose-positron emission
      tomography and computed tomography data sets in oral maxillofacial carcinoma:
      potential clinical value.
AB  - OBJECTIVE: The aim was to evaluate the clinical and therapeutic value of digital
      image fusion of 2-[18]-fluoro-2-deoxy-D-glucose (F18-FDG) positron emission
      tomography (PET) and computed tomography (CT) in patients suffering from an oral
      maxillofacial carcinoma. METHODS: Seventeen patients (11 male, 6 female; age
      range: 45-89 years) suffering from an oral maxillofacial carcinoma underwent CT
      and F18-FDG-PET (333-370 MBq). The data of the 2 imaging modalities were fused on
      an image workstation. This image fusion was then visualized in the axial,
      coronal, and sagittal planes. RESULTS: PET showed a high pathologic FDG uptake in
      the tumor in 17 of 17 patients. CT detected the tumor in 12 of 17 patients. The
      image fusion of FDG-PET and CT showed the tumor in 17 of 17 patients. The final
      diagnosis was carcinoma of the mandible in 9 of 17 patients, carcinoma of the
      mouth floor in 3 of 17 patients, carcinoma of the tongue in 3 of 17 patients,
      carcinoma of the roof of the mouth in 1 of 17 patients, and carcinoma of the
      parotis gland in 1 of 17 patients. CONCLUSIONS: Preoperative image fusion of FDG
      PET and CT data sets in oral maxillofacial carcinoma is possible in the clinical
      routine. Combined morphologic (CT) and functional (PET) imaging improves tumor
      localization even if the tumor is hardly visible on CT because of the artefacts
      of dental metallic implants (3/17 patients) or because of the small size of the
      tumor (2/17 patients). Image fusion is helpful for planning possible surgery
      (visual models) or radiotherapy (exact region of interest).

PMID- 14600458
TI  - Adhesive capsulitis of the shoulder: diagnosis using magnetic resonance
      arthrography, with arthroscopic findings as the standard.
AB  - OBJECTIVE: The purpose of this study was to assess the usefulness of magnetic
      resonance (MR) arthrography of the glenohumeral joint in the diagnosis of
      adhesive capsulitis. METHODS: MR arthrography of the glenohumeral joint was
      performed in 16 patients with arthroscopically proven adhesive capsulitis and 11
      controls. Thickness of the joint capsule and synovium, filling ratio of the fluid
      distended axillary recess to the posterior joint cavity, and a width of the
      rotator cuff interval were measured by 2 musculoskeletal radiologists. The
      measurements of those parameters for the patients with adhesive capsulitis and
      the controls were compared. Interobserver variability for the measurements of
      each parameter was calculated. RESULTS: The mean thickness of the joint capsule
      and synovium was 2.97 mm in patients with adhesive capsulitis and 1.86 mm in
      controls (P < 0.001). The mean filling ratio of the fluid-distended axillary to
      the posterior joint cavity was 0.51 in patients with adhesive capsulitis and 0.82
      in controls (P = 0.004). The mean width of the rotator cuff interval was 7.45 mm
      in patients with adhesive capsulitis and 8.48 mm in controls (P > 0.05).
      Intraclass correlation coefficient for interobserver variability showed good
      agreement (95% CI; 0.72-0.95). CONCLUSIONS: On MR arthrography, thickening of the
      joint capsule and synovium and diminished filling ratio of the axillary recess to
      posterior joint cavity appeared to be useful diagnostic criteria for the
      diagnosis of adhesive capsulitis of the shoulder.

PMID- 14600459
TI  - Detection of central pulmonary embolism on computed tomography densitometry
      images before computed tomography pulmonary angiography.
AB  - OBJECTIVE: The purpose of this article is to describe the imaging findings of
      acute central pulmonary embolism on computed tomography (CT) densitometry images
      performed before contrast-enhanced CT pulmonary angiography. METHODS: A
      retrospective review was conducted of reports from all CT pulmonary angiograms
      performed at our institution, and cases of acute central pulmonary embolism,
      defined as those with clot in the main, left, or right pulmonary arteries, were
      identified. Images of positive studies were reviewed on a picture archiving and
      communications system (PACS) workstation. RESULTS: A total of 1282 CT pulmonary
      angiograms were obtained for evaluation of possible acute pulmonary embolism, and
      1 combined CT aortogram and pulmonary angiogram was performed for aortic
      dissection and acute pulmonary embolism. Two hundred fourteen (16.7%)
      examinations positive for acute pulmonary embolism were identified, 26 (12.1%,
      2.0% of total examinations) of which had central clots. Of the 26 patients with
      central acute pulmonary embolism, 12 (46.1%, 5.6% of all positive studies and
      0.9% of all CT pulmonary angiograms) had clots that were visible on the
      densitometry images. CONCLUSION: Although an uncommon finding, acute central
      pulmonary embolism can be detected on CT densitometry performed to optimize
      opacification of the pulmonary arteries for CT pulmonary angiography and may
      prove useful in selected clinical situations.

PMID- 14600460
TI  - Mastoid and tympanic membrane as pressure buffers: a quantitative study in a
      middle ear cleft model.
AB  - HYPOTHESIS: The tympanic membrane (TM) and mastoid air cells are measurable
      pressure buffers of the middle ear (ME). BACKGROUND: Pressure homeostasis of the
      ME is maintained approximately atmospheric by mechanisms that neutralize (buffer)
      pressure fluctuations, two of which are the TM and mastoid. MATERIALS AND METHOD:
      Negative pressures were induced by volume changes in an artificial ME model.
      Those were recorded directly while using a rigid or a flexible TM with "mastoids"
      of various sizes. RESULTS: In the rigid TM model, the volume changes correlated
      linearly with the induced pressures and were confirmed to fit Boyle's law. In the
      flexible TM model, the pressure/volume correlation was nonlinear up to -50 mmH2O,
      where the TM was maximally displaced (approximately 25 mm3), became rigid, and
      constituted 75%, 41%, and 33% of the buffering gained in tandem with the
      "mastoid" in a model having a "mastoid" of 0, 5, and 10 mL, respectively.
      Altogether, a large "mastoid" required a greater volume change than a small one
      to induce the same pressure. CONCLUSIONS: The mastoid air volume "dilutes"
      pressure changes relatively to its size: the volume change required to alter a
      given pressure in an average (6 mL) mastoid is six-fold that which is needed in a
      small (1 mL) mastoid. ME volume reduction by TM retraction buffer negative ME
      pressures. This maximal ME volume change is constant for a "normal" TM.
      Therefore, it is the ME with the small mastoid that is most vulnerable to
      pressure changes and may develop compensatory buffering mechanisms, e.g.,
      additional TM retraction (atelectasis) and/or ME volume reduction by fluid
      accumulation.

PMID- 14600462
TI  - Tympanometry versus direct middle ear pressure measurement in an artificial
      model: is tympanometry an accurate method to measure middle ear pressure?
AB  - HYPOTHESIS: Indirect tympanometric pressure measurements of the middle ear (ME)
      do not correspond to direct pressure measurements. BACKGROUND: Tympanometry is an
      accepted method for estimating ME pressures. These pressure values are different,
      however, when measurements are made directly. MATERIALS AND METHODS: Negative
      pressures were induced by volume changes in an artificial ME model with various
      "mastoid" volumes. Both tympanometric and direct pressure measurements were
      obtained simultaneously. RESULTS: A substantial difference was demonstrated
      between tympanometric and direct pressure measurements. There was a linear
      correlation between tympanometry and direct pressures between -46.8 and -93.6
      mmH2O, with a tympanometric overestimation of 40% to 20%, respectively. The
      smaller the "mastoid" volume, the greater the overestimation. The correlation was
      not linear for direct pressures between zero and -46.8 mmH2O. Tympanometric
      overestimation was greatest (i.e., 4-14-times the actual pressure) in the
      pressure range between zero and -12 mmH2O. CONCLUSIONS: Tympanometry does not
      yield precise ME pressure values. In a model with a larger "mastoid" and an
      actual pressure range of -46.8 to -93.6 mmH2O tympanometric readings are somewhat
      less unreliable (error of 40%-20%). However, tympanometry is in error of more
      than 400% in a model with a small mastoid in which the actual ME pressure is only
      slightly negative (i.e., range between -3.9 and -46.8 mmH2O). Therefore, this
      study implies that tympanometry has little use for measuring ME pressure
      especially in chronic ears or their sequelae that are usually characterized by
      having small negative pressures and small mastoids.

PMID- 14600461
TI  - Temporal bone infection caused by atypical mycobacterium: case report and review
      of the literature.
AB  - OBJECTIVE: To discuss the clinical aspects and management of nontuberculous
      mycobacteriosis of the temporal bone. STUDY DESIGN: Case report and review of the
      literature. SETTING: University hospital, tertiary referral center. PATIENT,
      INTERVENTION, AND RESULTS: The authors describe an uncommon case of
      nontuberculous mycobacteriosis of the temporal bone in an immunosuppressed 62
      year-old woman with facial nerve paralysis caused by disease complication. The
      case was cured with radical tympanomastoidectomy and prolonged multiple
      antibiotic therapy. CONCLUSIONS: Nontuberculous mycobacteriosis should be
      suspected in immunosuppressed patients with intractable middle ear granulations.
      Cultural and histologic examinations are the mainstay for diagnosis. Long
      standing multiantibiotic therapy together with aggressive surgery should be
      considered as appropriate management.

PMID- 14600463
TI  - Increased activity of the diastrophic dysplasia sulfate transporter in
      otosclerosis and its inhibition by sodium fluoride.
AB  - HYPOTHESIS: This study investigates the function of the diastrophic dysplasia
      sulfate transporter (DTDST) in otosclerotic bone and the effect on it of sodium
      fluoride (NaF). BACKGROUND: Otosclerosis is a localized bone dystrophy with
      increased bone turnover. DTDST is implicated in the regulation of the bone
      turnover. MATERIALS AND METHODS: Primary cultures of cells were obtained from the
      stapes and external auditory canal (EAC) of 26 patients with otosclerosis and
      from nine control patients. Sulfate uptake was quantified under basal conditions
      and with NaF. The NaF signaling pathways were investigated using forskolin and
      verapamil. RESULTS: The relative initial rates of sulfate uptake and the apparent
      Vmax values were: otosclerotic stapes > EAC > control stapes = control EAC. The
      sulfate uptake by the otosclerotic stapes was correlated with the loss of
      sensorineural hearing. The amounts of DTDST mRNA (RNase protection assay) in the
      four subgroups did not differ. NaF (10(-6)M, 1 hr) inhibited sulfate uptake by
      the otosclerotic stapes and EAC cells but not by control samples. CONCLUSION: The
      authors believe that whether the increased DTDST activity is a cause or an effect
      of otosclerosis, it appears to be a specific target for NaF treatment.

PMID- 14600464
TI  - Retrospective analysis of early postoperative hearing results obtained after
      stapedotomy with implantation of a new titanium stapes prosthesis.
AB  - OBJECTIVE: To evaluate the early postoperative hearing results of a new titanium
      stapes prosthesis (K-Piston) implanted in patients with otosclerosis. STUDY
      DESIGN: A retrospective analysis of preoperative and early postoperative hearing
      thresholds. SETTING: One tertiary referral and teaching hospital. PATIENTS:
      Eighteen men and 40 women, mean age 47 years, with otosclerosis. INTERVENTION:
      Primary stapedotomy. MAIN OUTCOME MEASURE: Main outcome measures were the mean
      gains in bone-conduction and air-conduction pure-tone thresholds, and pure-tone
      averages for different frequency combinations. Success and failure of the
      individual cases were presented using Amsterdam Hearing Evaluation Plots.
      RESULTS: The overall postoperative air-bone gap for the frequency combination 0.5
      1-2-4 kHz was 8.4 (standard deviation: 5.2) dB. In 79% of the patients the
      postoperative air-bone gap was less than 10 dB. Air-conduction improved even in
      higher frequencies, while the Carhart effect was not seen in most cases. In three
      patients a deterioration of bone-conduction was observed ranging from 11 to 16 dB
      sound pressure level (SPL), and in four patients the gain in air-conduction was
      insufficient (3-29 dB SPL) to close the preoperative air-bone gap to within 20
      dB. CONCLUSION: The new low-weight, full-titanium stapes prosthesis with its
      slight rough surface and its good mechanical stability and biocompatibility can
      safely and successfully restore the function of the middle ear when implanted in
      patients with otosclerosis.

PMID- 14600465
TI  - Do the genes that cause otosclerosis reduce susceptibility to otitis media?
AB  - HYPOTHESIS: The genetic factors that cause otosclerosis reduce susceptibility to
      otitis media. BACKGROUND: Susceptibility to some infectious diseases is modulated
      by host genetic factors. Genes that reduce the morbidity and mortality of
      infectious diseases may confer a selective advantage and achieve high-frequency
      in at-risk populations. Acute otitis media in the pre-antibiotic era frequently
      led to complications with high morbidity and mortality. The long-term sequela of
      acute otitis media is chronic otitis media. Chronic otitis media has a prevalence
      of 0.5 to 2 percent in the Caucasian population. Clinical otosclerosis occurs in
      1 percent of Caucasians. Histologic otosclerosis occurs in 10 percent of
      Caucasians. MATERIALS AND METHODS: Retrospective analysis of 2,362 subjects with
      surgically confirmed otosclerosis. Subjects' medical records were reviewed for
      evidence of chronic otitis media. The incidence of chronic otitis media in the
      general population was compared with the subject population. RESULTS: Of the
      2,362 subjects with surgically confirmed otosclerosis, one subject with evidence
      of chronic otitis media was identified. The incidence of chronic otitis media in
      the subject population is 0.04 percent (p < 0.0001). CONCLUSIONS: The incidence
      of chronic otitis media in subjects with a surgically confirmed diagnosis of
      otosclerosis is significantly lower than expected. The genes that cause
      otosclerosis may confer resistance to the pathogens that cause chronic otitis
      media and/or acute otitis media. The mechanism of resistance is unknown.

PMID- 14600468
TI  - Fluoroscopically assisted cochlear implantation.
AB  - HYPOTHESIS: Real-time intraoperative fluoroscopy is a useful adjunct to cochlear
      implantation in selected cases. The advantages include the avoidance of
      complications such as extracochlear array placement, intrameatal array insertion,
      and avoidance of significant bending or kinking. This is particularly useful when
      implanting a severely abnormal cochlea. BACKGROUND: The technique was initially
      developed for laboratory study of electrode prototypes in cadaver temporal bones
      to evaluate insertion dynamics and mechanisms of intracochlear trauma. The
      technique was subsequently adapted for use in live surgeries. METHODS: Live
      surgeries were performed using fluoroscopic guidance on nine patients. RESULTS:
      Five patients were implanted with the Nucleus 24 RCS during preclinical trials.
      Two patients with severe cochlear malformations were implanted with a Nucleus
      CI24M straight array. Two patients with severe cochlear ossification were
      implanted with the Nucleus CI24 double array. Appropriate insertions were
      achieved without electrode damage in all cases. CONCLUSIONS: Intraoperative
      fluoroscopy is a useful adjunct to cochlear implantation, which can be performed
      with minimum risk to the patient and operating room staff if the outlined
      precautions are taken. Intraoperative fluoroscopy is indicated in cases where the
      intracochlear behavior of the electrode array cannot be predicted, a condition
      encountered when implanting new electrode designs, cases with severely malformed
      inner ears, or cases of severe intraluminal obstruction requiring a double-array
      insertion.

PMID- 14600467
TI  - Psychologic profile of tinnitus patients using the SCL-90-R and Tinnitus Handicap
      Inventory.
AB  - OBJECTIVE: To correlate the Tinnitus Handicap Inventory and the Symptom Checklist
      90-R results on a group of tinnitus patients and to compare the average scores of
      the Tinnitus Handicap Inventory and SCL-90-R for help-seeking and non-help
      seeking patients with tinnitus. STUDY DESIGN: A prospective study in which
      tinnitus patients were administered the Tinnitus Handicap Inventory and the
      Symptom Checklist-90-R. SETTING: Tertiary referral center. PATIENTS: Patients
      with tinnitus seeking audiological services. INTERVENTIONS: Rehabilitative. MAIN
      OUTCOME MEASURES: Results of Tinnitus Handicap Inventory and Symptom Checklist-90
      R. RESULTS: Fifty-three consecutive patients having tinnitus were administered
      the Tinnitus Handicap Inventory and the Symptom Checklist-90-R. There was a
      significant correlation between the Symptom Checklist-90-R and the Tinnitus
      Handicap Inventory (rs = 0.43). Furthermore, 25% of these patients scored
      abnormally high on the Symptom Checklist-90-R, which is substantially more than
      the general medical population of patients. CONCLUSIONS: Based on this sample of
      53 patients, the Symptom Checklist-90-R does seem to be a useful tool in
      identifying distress among tinnitus patients. The Global Severity Index of the
      Symptom Checklist-90-R has a defined cutoff score indicating significant distress
      levels, which makes it a useful screening tool for identifying those who would
      benefit from psychologic or psychiatric intervention.

PMID- 14600466
TI  - Auditory processing in patients with Charcot-Marie-Tooth disease type 1A.
AB  - HYPOTHESIS: It is unclear whether Charcot-Marie-Tooth (CMT) disease, type 1A,
      causes auditory processing disorders. Therefore, auditory processing abilities
      were investigated in five CMT1A patients with normal hearing. BACKGROUND:
      Previous studies have failed to separate peripheral from central auditory
      processing disorders. MATERIALS AND METHODS: Five genetically confirmed CMT1A
      cases in patients with normal hearing underwent behavioral and objective testing.
      Pure tone audiometry, speech audiometry, and OAE assessment were followed-up by
      an auditory processing test battery comprising sentences-in-noise test, pattern
      recognition tests, words-in-noise test, dichotic digit test, filtered speech
      test, binaural fusion test, and categorical speech perception test. Subsequently,
      ABR and ERP measurements were conducted. RESULTS: Either the behavioral or
      objective test scores of 4 out of the 5 CMT1A patients did not differ
      significantly from those of subjects with normal hearing. Significantly lower
      scores of one patient on auditory processing tests and ABR measurements could be
      ascribed to subnormal hearing. CONCLUSION: The authors conclude that CMT1A
      patients with normal peripheral hearing have auditory processing abilities that
      were not indicative for an auditory processing disorder. Furthermore, the
      presence of a peripheral hearing loss complicates the interpretation of auditory
      processing abilities.

PMID- 14600469
TI  - Cochlear implants in aplasia and hypoplasia of the cochleovestibular nerve.
AB  - OBJECTIVE: To report on the outcome of four patients with aplasia or hypoplasia
      of the cochleovestibular nerve who have received a cochlear implant. STUDY
      DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENTS:
      Four patients with: 1) type I aplasia; 2) type IIa aplasia; 3) type IIa
      hypoplasia; and 4) type IIb aplasia received a cochlear implant. All patients had
      corner audiograms even with hearing aids. INTERVENTION: Three patients received a
      LAURA multichannel implant, and one patient received a Nucleus 24 implant. MAIN
      OUTCOME MEASURE: Auditory performance, educational setting. RESULTS: The patients
      with type I and type IIb aplasia did not have auditive perception with their
      implant and became non-users. Both are now in a total communication educational
      setting. The patients with type IIa aplasia and hypoplasia had moderate
      audiological results with the implant with audiometrical thresholds of
      approximately 40-60 dB HL (pure tone average), moderate phoneme discrimination,
      and poor word discrimination. One child is in a total communication educational
      setting and the other in an oral educational setting, but the preferred mode of
      communication remains total communication for both. Both appear to benefit from
      the implant nonetheless. CONCLUSION: Patients with aplasia/hypoplasia of the
      cochleovestibular nerve should be counseled with caution with respect to cochlear
      implantation, but particular circumstances may justify the intervention. At
      present these circumstances seem to be a type IIa aplasia or hypoplasia in which
      the end organ (cochlea or common cavity) still connects to a neural structure on
      MRI.

PMID- 14600470
TI  - Cochlear implantation in human immunodeficiency virus-infected patients.
AB  - OBJECTIVE: To evaluate the efficacy of cochlear implants in human
      immunodeficiency virus-infected individuals and correlate these results with a
      proposed pathophysiological mechanism of human immunodeficiency virus-associated
      hearing loss. STUDY DESIGN: Retrospective case series and temporal bone analysis
      of deceased human immunodeficiency virus-positive patients. SETTING: Tertiary
      care hospital. PATIENTS: Seven human immunodeficiency virus-positive individuals
      with profound sensorineural hearing loss. INTERVENTION: Cochlear implantation at
      New York University Medical Center. METHODS: The surgical outcomes and
      complications were analyzed. Additionally, electron microscopic and
      immunohistochemical findings of cadaver temporal bone specimens of other known
      human immunodeficiency virus-positive individuals were reviewed. The performance
      results of the human immunodeficiency virus-positive cochlear implant patients
      were then correlated with the previously hypothesized pathophysiological
      mechanism of human immunodeficiency virus-associated hearing loss. RESULTS: The
      patients had a varied performance with cochlear implantation, and as a group
      performance was good. There were no surgical complications or postoperative
      complications. The good performance of these patients supports the hypothesis
      that the mechanism of human immunodeficiency virus-associated deafness involves
      infiltration, malfunction, and premature degeneration of the hair cells and
      supportive cells of the cochlea. CONCLUSIONS: Human immunodeficiency virus
      positive individuals benefit from cochlear implantation without increased
      surgical risk.

PMID- 14600471
TI  - Intracerebral abscess after abutment change of a bone anchored hearing aid
      (BAHA).
AB  - OBJECTIVE: Brain abscesses are life-threatening and sometimes difficult to
      detect. A brain abscess after placement, manipulation of a bone anchored hearing
      aid, or a periauricular implant for fixation of an ear prosthesis has never been
      reported in the literature. PATIENT: A 42-year-old man suffered from a right
      sided temporodorsal brain abscess after change of a bone anchored hearing aid
      abutment. The fixture itself had been inserted 8 years before without any
      complications in the peri- or postoperative period. A CT-guided puncture of the
      abscess could be performed via the screw-hole in the temporal bone after removal
      of the fixture, and the patient was treated with antibiotics. RESULTS: The
      outcome of the procedure was good without neurologic deficits for the patient.
      CONCLUSION: The insertion of periauricular screw implants bears the risk of
      meningeal lesions as well as a small risk of purulent intracranial and
      intracerebral complications perioperatively or in the context of later
      manipulations. Minimally invasive therapy of such brain abscesses can be
      performed by removal of the foreign body, CT-guided puncture, and antibiotic
      medication.

PMID- 14600474
TI  - Head-impulse and caloric tests in patients with dizziness.
AB  - OBJECTIVE: To test the performance of the head-impulse and caloric tests in terms
      of sensitivity, specificity, and predictive efficiency. STUDY DESIGN: This was an
      open and prospective study conducted at a tertiary care center in which 265
      patients were subjected to the head-impulse test and caloric test on the same
      day. The results of the head-impulse test were considered as normal or
      pathologic. In a similar way, the caloric test was rated as normal when the
      difference in canal paresis was less than 22 percent and directional
      preponderance less than 28 percent, and abnormal if canal paresis was more than
      22 percent and/or directional preponderance was more than 28 percent. MAIN
      OUTCOME MEASURES: The results of each test were compared with obtain the
      specificity, sensitivity, and positive and negative predictive values. A receiver
      operating characteristics (ROC) curve was obtained from the false-alarm rate and
      the hit rate value of the head impulse test. RESULTS: The specificity of the head
      impulse test was 0.91 and the sensitivity was 0.45. The positive predictive value
      was 0.92, the negative predictive value was 0.41, and the area under the ROC
      curve was 0.866. A canal paresis value of 42.5 percent was considered to be the
      limit of the normal response, as seen when the head impulse test was used to
      predict a normal or abnormal result in a given patient. CONCLUSION: The head
      impulse test, when used as a bedside test, and the caloric test are by no means
      redundant methods. The information obtained form both can be used in combination
      to obtain a better insight into the degree of vestibular dysfunction of patients.

PMID- 14600472
TI  - Congenital aural atresia in 18q deletion or de Grouchy syndrome.
AB  - OBJECTIVE: To study the occurrence of congenital aural atresia in patients with a
      deletion of the long arm of chromosome 18 (18q- deletion or de Grouchy syndrome).
      STUDY DESIGN AND PATIENTS: This retrospective study presents an overview of the
      otologic findings in 33 Dutch and Belgian patients with a deletion of 18q.
      MATERIALS AND METHODS: Detailed information on otorhinolaryngological findings
      was obtained from otorhinolaryngologists and audiologic centers. Data about
      medical and developmental history and phenotype were collected from physical
      examination by a clinical geneticist, by interviewing parents, and by reviewing
      medical and developmental records. Determination of deletion breakpoints was
      established by routine karyotyping, prometaphase studies, and/or fluorescence in
      situ hybridization (FISH). RESULTS: Twenty out of 33 patients (61%) with a
      deletion 18q had congenital aural atresia (CAA) ranging from narrow external
      auditory canals to meatal atresia type IIB. Fifteen patients (45%) had conductive
      hearing impairment (range: 30 dB-70 dB). Twelve of these 15 patients (80%)
      received hearing aids, which resulted in improved hearing but not in speech
      development. CAA was found only in patients with a distal deletion of 18q
      (including band 18q22.3 or 18q23) and not in patients with more proximal 18q
      deletions. CONCLUSION: In patients with narrow ear canals or meatal atresia and
      unexplained mental retardation, chromosomal analysis is indicated. If de Grouchy
      syndrome is diagnosed in a young patient, auditory examination and surveillance
      are highly recommended.

PMID- 14600473
TI  - Sensorineural hearing loss in postmeningitic children.
AB  - OBJECTIVE: To establish the proportion of children who develop sensorineural
      hearing loss after bacterial meningitis and to correlate such loss with patient
      factors. STUDY DESIGN: Retrospective case review. SETTING: McMaster University
      Children's Hospital, a tertiary referral center. PATIENTS: Children between the
      ages of 1 day and 18 years admitted to McMaster University Children's Hospital
      with a confirmed diagnosis of bacterial meningitis between January 1, 1991 and
      December 30, 2000. INTERVENTIONS: Audiological assessment including auditory
      brainstem responses and cortical electric-response audiometry or standard
      audiometry. MAIN OUTCOME MEASURES: The nature of sensorineural hearing loss was
      assessed according to the degree (mild to profound) and course (transient versus
      permanent). Correlations between sensorineural hearing loss and the patient's
      age, sex, duration of illness before admission, use of dexamethasone, concurrent
      neurologic complications, and types of pathogens were evaluated. Patterns of
      inpatient and outpatient audiological assessment were determined. RESULTS:
      Seventy-nine children had confirmed bacterial meningitis. Streptococcus
      pneumoniae accounted for 36.7 percent of all cases, followed-up by Neisseria
      meningitides (16.5%), group B Streptococcus (15.2%), and Hemophilus influenzae
      (13.9%). Sixty-eight (86.1%) children underwent hearing assessment, either as
      inpatients or after discharge. Of the remaining 11 (13.9%) in whom audiological
      evaluation could not be confirmed, only two made mention of a referral. As such,
      a nonreferral rate of 11.4 percent was identified. Abnormal auditory brainstem
      response findings were present in 22 cases (32.3%), with 11 cases (13.9%) of
      permanent sensorineural hearing loss identified. A statistically significant
      association between sensorineural hearing loss and Streptococcus pneumoniae was
      found (p < 0.001). No association between age, sex, duration of illness before
      admission, use of dexamethasone, and number of concurrent neurologic
      complications could be established. CONCLUSIONS: In our series, 11 children
      (13.9%) experienced permanent sensorineural hearing loss, consistent with
      previously reported rates of 5 to 35 percent within the pediatric population.
      Since introduction of the Hemophilus influenzae type B vaccine, Streptococcus
      pneumoniae has emerged as the dominant causative organism of bacterial meningitis
      in children. Our study additionally confirms the role of Streptococcus pneumoniae
      as a precipitant of sensorineural hearing loss (p < 0.001). Audiological
      assessment in our series (86.1%) exceeds most of the screening rates previously
      reported in the literature. Because of compliance problems with outpatient
      audiological assessment and because early identification and expedient
      amplification lead to better academic and language outcomes, routine inpatient
      audiological screening of postmeningitic children is advocated.

PMID- 14600476
TI  - Middle fossa versus retrosigmoid-transmeatal approach in vestibular schwannoma
      surgery: a prospective study.
AB  - OBJECTIVE: To compare the advantages, disadvantages, and results obtained with
      the middle fossa and retrosigmoid-transmeatal approaches during pure intracanalar
      vestibular schwannoma surgery in an attempt to preserve hearing. STUDY DESIGN:
      Prospective study of patients treated from 1998 to 2001. SETTING: Tertiary care
      referral center. PATIENTS: Patients with intracanalar vestibular schwannoma (size
      ranging from 4 to 12 mm), 25 operated on with the retrosigmoid-transmeatal
      technique and 25 via the middle fossa route. MAIN OUTCOME MEASURES: Facial nerve
      and auditory function were examined at 1 year with both techniques. Auditory
      results were also evaluated as a function of tumor size, distance from the
      internal auditory canal fundus, and internal auditory canal enlargement. RESULTS:
      The results indicated no significant difference in facial nerve and auditory
      function results between the two techniques. The retrosigmoid-transmeatal
      approach, however, yielded better facial nerve function results at discharge.
      Postoperative hearing was better when the distance from the fundus was greater
      than 3 mm, when the size of the vestibular schwannoma was equal to or less than 7
      mm, and when the internal auditory canal enlargement was less than 3 mm.
      CONCLUSIONS: The middle fossa approach does not afford any particular advantages
      over the retrosigmoid-transmeatal approach in terms of auditory results. Facial
      nerve function is less satisfactory in the short term, when the middle fossa
      route is used, but can be improved by decompression and gentle displacement of
      the facial nerve in its labyrinthine portion.

PMID- 14600475
TI  - Preventing internal auditory artery vasospasm using topical papaverine: an animal
      study.
AB  - BACKGROUND: Internal auditory artery (IAA) spasm is thought to be one of the
      causes of postoperative sensory hearing loss after attempted hearing preservation
      removal of an acoustic neuroma. The use of topical papaverine, a nonspecific
      vasodilator, to prevent vascular insufficiency to the inner ear and to improve
      hearing outcomes has been suggested but not proven. MATERIALS AND METHODS:
      Vasospasm was mechanically induced by compressing the IAA in the control ears of
      six rabbits after application of topical saline. The subsequent reduction of
      cochlear blood flow (CBF) was measured using a laser-Doppler (LD) flow-monitoring
      technique. Functional loss of cochlear activity was verified with distortion
      product otoacoustic emissions (DPOAE). The contralateral experimental ears were
      treated with the topical application of papaverine directly to the IAA and
      cochleovestibular nerve complex. CBF and DPOAE were compared between the control
      and papaverine treated ears for 3-minute and 5-minute IAA compressions. RESULTS:
      Every control ear demonstrated some degree of postcompression IAA vasospasm
      (i.e., reduced CBF) and reduction of DPOAE. Nearly complete recovery of CBF and
      DPOAE to baseline was observed in all of the papaverine treated ears.
      CONCLUSIONS: An animal model of IAA vasospasm was described. Mechanically induced
      vasospasm of the IAA was prevented by the topical application of papaverine.
      These findings have clinical implications for surgical procedures involving the
      internal auditory canal/cerebellopontine angle such as acoustic neuroma removal.

PMID- 14600477
TI  - Anomalous vein in the middle cranial fossa associated with the tegmen tympani
      defect.

PMID- 14600478
TI  - Image-guided endoscopic transsphenoidal drainage of select petrous apex
      cholesterol granulomas.
AB  - OBJECTIVE: Explore the indications and advantages of image-guided transsphenoidal
      endoscopic drainage of select petrous apex cholesterol granulomas. STUDY DESIGN:
      Case report and literature review. SETTING: Tertiary referral center.
      CONCLUSIONS: Image-guided endoscopic transsphenoidal drainage of cholesterol
      granulomas is the procedure of choice for petrous apex cholesterol granulomas
      that abut the sphenoid sinus and are accessible through its posterior wall.

PMID- 14600479
TI  - Facial nerve tumors.
AB  - OBJECTIVE: To evaluate the surgical results in primary facial nerve (FN) tumors.
      STUDY DESIGN: Retrospective case review. SETTING: Private neuro-otological and
      skull-base tertiary referral center. PATIENTS: Twenty eight consecutive patients
      affected by primary FN tumors that underwent surgery between December 1990 and
      February 2001. INTERVENTIONS: The lesions were removed through a variety of
      surgical approaches, depending on tumor location and extension, as well as
      preoperative hearing. In one case, partial removal was performed. MAIN OUTCOME
      MEASURES: Preoperative and postoperative FN function; preoperative and
      postoperative hearing level; and postoperative complications. RESULTS: Based on
      histologic examination, tumors were distributed as follows: 18 schwannomas, six
      hemangiomas, two meningiomas, and two neurofibromas. Tumor location varied, with
      lesions distributed along the entire length of the nerve. Facial dysfunction was
      the most frequently recorded symptom, followed by hearing loss. Only five
      patients presented a preoperative grade 1 facial function. In the remaining
      patients of the group, the facial deficit lasted from 2 to 120 months, with a
      mean of 31.2 months. Anatomic integrity of the nerve was preserved in 4 cases;
      all others required a nerve interruption followed by reconstruction using a sural
      nerve graft. The complications recorded were: one cerebrospinal fluid leak, one
      postoperative retraction pocket, and one external auditory canal wall resorption
      requiring a surgical revision. Preoperative hearing remained unchanged in 8 out
      of the 15 patients in whom a hearing preservation procedure was attempted. In 25
      cases, a follow-up of equal to or longer than 1 year was available, with the FN
      functions: two grade 1, eight grade 3, nine grade 4, three grade 5, and three
      grade 6. Patients with a preoperative deficit lasting more than 1 year
      demonstrated the worst recovery. CONCLUSIONS: Primary FN tumors are rare lesions
      that include different histologic types. FN deficit represents the most common
      symptom, but it is not present in all cases. A conservative strategy is often
      adopted in presence of a normal preoperative facial function. When surgical
      management is selected, the decision on surgical approach to use depends on tumor
      size and location, as well as on preoperative hearing. FN integrity may be spared
      in rare occasions, but more frequently nerve reconstruction is required. Final
      facial function recovery is mainly dependent on the preoperative presence of FN
      deficit and its duration.

PMID- 14600480
TI  - Efficacy of early treatment of Bell's palsy with oral acyclovir and prednisolone.
AB  - OBJECTIVE: To investigate the therapeutic effects of acyclovir and prednisolone
      in relation to the timing of treatment in Bell's palsy. STUDY DESIGN: This was a
      retrospective study of 480 Bell's palsy patients who were treated with oral
      acyclovir and prednisolone (94 cases) or prednisolone alone (386 cases).
      PATIENTS: Patients met the after criteria: (1) severe or complete Bell's palsy
      with a score lower than 20 on the 40-point Yanagihara facial score and (2)
      treatment started within 7 days after onset. The patients were treated with oral
      prednisolone (60-40 mg/day) with or without oral acyclovir (2,000 mg/day). MAIN
      OUTCOME MEASURE: Rate of recovery, which was defined as a facial score of 36 or
      more, and the absence of contracture with synkinesis. RESULTS: The overall
      recovery rate of patients treated with acyclovir and prednisolone was 95.7
      percent, which was better than that of patients treated with prednisolone alone
      (88.6%). The recovery rate in patients who began the combined therapy within 3
      days of the onset of palsy was 100 percent and early treatment resulted in early
      remission. In contrast, the recovery rate in patients who started the combined
      therapy more than 4 days after onset was 86.2 percent. CONCLUSION: These results
      suggest that early diagnosis and treatment within 3 days of the onset of
      paralysis are necessary for maximal efficacy of combined acyclovir and
      prednisolone therapy for Bell's palsy.

PMID- 14600482
TI  - Cochlear involvement in a temporal bone fracture.

PMID- 14600481
TI  - A translation of: The scientific progress of otology in the past decennium (until
      late 1862) by Hermann Schwartze: pathology and therapy of the external ear.
AB  - In 1863, Anton von Troltsch, Adam Politzer, and Hermann Schwartze began the first
      journal dedicated solely to disorders of the ear, Archiv fur Ohrenheilkund
      (Archives of Otology). In the inaugural edition, Hermann Schwartze, the youngest
      of the three, took on the responsibility for summarizing all the prevailing
      advances in otology recorded in the previous 10 years leading up to its
      publication. This work represents a concise summary of all major advances and
      theories regarding diseases of the ear circa 1863, providing a valuable window on
      the practice of otology during its inception as an independent subspecialty. In
      this first of an anticipated two-part article, we provide a translation of what
      is perhaps the most interesting portion: pathology and therapy of the outer ear
      and middle ears. The second part of the manuscript will translate the pathology
      and treatment of inner ear disorders. It is hoped that this work will spark
      contemporary otologists not only to reflect how far we have come as a
      subspecialty but also to reflect what we still must accomplish as physicians and
      scientists.

PMID- 14600483
TI  - Osteoma of the external ear canal.

PMID- 14600485
TI  - Extramedullary hematopoiesis presenting as a middle ear mass.

PMID- 14600484
TI  - Enlarged bony portion of the eustachian tube in oculoauriculovertebral spectrum.

PMID- 14600486
TI  - Acoustic trauma.

PMID- 14600488
TI  - Are neural correlates of visual consciousness retinotopic?
AB  - Some visual neurons code what we see, their defining characteristic being a
      response profile which mirrors conscious percepts rather than veridical sensory
      attributes. One issue yet to be resolved is whether, within a given cortical
      area, conscious visual perception relates to diffuse activity across the entire
      population of such cells or focal activity within the sub-population mapping the
      location of the perceived stimulus. Here we investigate the issue in the human
      brain with fMRI, using a threshold stimulation technique to dissociate perceptual
      from non-perceptual activity. Our results point to a retinotopic organisation of
      perceptual activity in early visual areas, with independent perceptual
      activations for different regions of visual space.

PMID- 14600487
TI  - Submucosal cholesteatoma in the middle ear: a histopathologic observation.

PMID- 14600492
TI  - Phonological processing in language production: time course of brain activity.
AB  - Recent neuroimaging studies provide evidence for a shared neural network for
      phonological processing in language production and comprehension. The temporal
      dynamics in this network during comprehension has been investigated by Thierry et
      al., who showed a primacy for Wernicke's over Broca's area. In the present study,
      we demonstrate the reversed pattern for language production. These results can be
      interpreted with respect to the functionality of the different regions within the
      shared network, with Wernicke's area being the sound form store and Broca's area
      a processor necessary to extract relevant phonological information from that
      store.

PMID- 14600489
TI  - Kainic acid upregulates uncoupling protein-2 mRNA expression in the mouse brain.
AB  - Intraperitoneal injection of kainic acid (KA) in C57BL/6J and 129T2SvEmsJ mice
      led to a transient induction of uncoupling protein-2 (Ucp2) mRNA expression in
      several brain regions, which included the CA1 subfield of the hippocampus, the
      dorsal endopiriform nucleus and the piriform cortex in both strains. In all those
      regions, levels of Ucp2 mRNA expression, as determined by in situ hybridization,
      peaked at 24 h and returned to basal levels within 72 h post-injection. The
      increase in mRNA expression was mainly observed in neurons, with microglial cells
      displaying only scattered expression of the gene. The neuronal induction of Ucp2
      in response to KA was stronger in 129T2SvEmsJ mice than in C57BL/6J, which
      suggests a role for Ucp2 in excitotoxic challenges and neuroprotection.

PMID- 14600490
TI  - Effects of a 902 MHz mobile phone on cerebral blood flow in humans: a PET study.
AB  - Fourteen healthy right-handed subjects were scanned using PET with a [15O]water
      tracer during exposure to electromagnetic field (EMF) emitted by a mobile phone
      and a sham-exposure under double-blind conditions. During scanning, the subjects
      performed a visual working memory task. Exposure to an active mobile phone
      produced a relative decrease in regional cerebral blood flow (rCBF) bilaterally
      in the auditory cortex but no rCBF changes were observed in the area of maximum
      EMF. It is possible that these remote findings were caused by the EMF emitted by
      the active mobile phone. A more likely interpretation of the present findings
      were a result of an auditory signal from the active mobile phone. Therefore, it
      is not reasoned to attribute this finding to the EMF emitted by the phone.
      Further study on human rCBF during exposure to EMF of a mobile phone is needed.

PMID- 14600491
TI  - MRI study of white matter diffusion anisotropy in schizophrenia.
AB  - Diffusion tensor imaging (DTI) can provide information about brain white matter
      integrity. The results of DTI studies in schizophrenia are somewhat variable and
      could benefit from standardized image processing methods. Fourteen patients with
      schizophrenia or schizoaffective disorder and 14 healthy volunteers underwent
      DTI. Scans were analyzed using a rigorous voxelwise approach. The key dependent
      variable, fractional anisotropy, was lower for patients in the corpus callosum,
      left superior temporal gyrus, parahippocampal gyri, middle temporal gyri,
      inferior parietal gyri, medial occipital lobe, and the deep frontal perigenual
      region. Regions showing reduced white matter fractional anisotropy are known to
      be abnormal in schizophrenia. The voxelwise method used in the current study can
      provide the basis for hypothesis-driven research.

PMID- 14600493
TI  - Stepwise emergence of the face-sensitive N170 event-related potential component.
AB  - The present study used a parametric design to characterize early event-related
      potentials (ERP) to face stimuli embedded in gradually decreasing random noise
      levels. For both N170 and the vertex positive potential (VPP) there was a linear
      increase in amplitude and decrease in latency with decreasing levels of noise. In
      contrast, the earlier visual P1 component was stable across noise levels. The
      P1/N170 dissociation suggests not only a functional dissociation between low and
      high-level visual processing of faces but also that the N170 reflects the
      integration of sensorial information into a unitary representation. In addition,
      the N170/VPP association supports the view that they reflect the same processes
      operating when viewing faces.

PMID- 14600496
TI  - Human auditory cortex tracks task-irrelevant sound sources.
AB  - The brain organizes sound into coherent sequences, termed auditory streams. We
      asked whether task-irrelevant sounds would be detected as separate auditory
      streams in a natural listening environment that included three simultaneously
      active sound sources. Participants watched a movie with sound while street-noise
      and sequences of naturally varying footstep sounds were presented in the
      background. Occasional deviations in the footstep sequences elicited the mismatch
      negativity (MMN) event-related potential. The elicitation of MMN showed that the
      regular features of the footstep sequences had been registered and their
      violations detected, which could only occur if the footstep sequence had been
      detected as a separate auditory stream. Our results demonstrate that sounds are
      organized into auditory streams irrespective of their relevance to ongoing
      behavior.

PMID- 14600495
TI  - Cortical sound processing in children with autism disorder: an MEG investigation.
AB  - Previous work investigating frequency encoding mechanisms in human auditory
      cortex has provided evidence that latency of the auditory evoked M100 is strongly
      proportional to frequency, with low frequency (100-200 Hz) tones associated with
      approximately 30 ms longer latencies than mid-range frequency (1-2 kHz) tones.
      Motivated by pervasive speech and auditory perception deficits observed in autism
      spectrum disorder, we evaluated M100 frequency dependence in children with autism
      disorder and typically developing controls. Results indicate that for control
      children, the dynamic range of frequency modulation was similar to previous
      reports for healthy adults. Children with autism had a much reduced range of
      modulation in right hemisphere sites. Findings indicate that frequency encoding
      mechanisms may follow a differential maturational path in autism spectrum
      disorder.

PMID- 14600494
TI  - P-glycoprotein and caveolin-1alpha in endothelium and astrocytes of primate
      brain.
AB  - P-glycoprotein (P-gp) and caveolin-1alpha are both involved in membrane
      transport, and studies in rodent brain show that these proteins are specifically
      localized at the microvascular endothelium, which forms the blood-brain barrier
      (BBB). In humans, P-gp is also expressed in astrocytes, especially in
      pathological tissue. The present study examines the cellular expression of P-gp
      and caveolin-1alpha in fresh-frozen brain from healthy rhesus monkey using
      confocal microscopy and polyclonal antibodies against either P-gp or caveolin
      1alpha co-labeled for astrocytes or microvascular endothelium. P-gp and caveolin
      1alpha are expressed in both astrocytes and endothelium of healthy primate brain.
      These findings suggest that P-gp and caveolin-1alpha share a broad spectrum of
      cellular expression and may play a role in drug transport within the brain in
      addition to the BBB.

PMID- 14600497
TI  - Intralimb incoordination in patients with ataxia.
AB  - Intralimb incoordination needs to be distinguished from interlimb incoordination,
      which is observed in Parkinson's disease (PD). With this aim, intra and inter
      limb coordination impairment in the lower limbs were measured in 13 patients with
      cerebellar ataxia during pedaling of an ergometer with left and right pedals that
      can be rotated independently. Intralimb incoordination in patients with
      cerebellar ataxia was compared with interlimb incoordiation in patients with PD.
      We concluded that impairment of intralimb coordination in ataxia patients leads
      to inability to maintain pedaling amplitude and speed, but unlike in PD, right
      and left coordination was roughly preserved. Our method may be useful for
      assessing the severity of ataxia and detecting hidden parkinsonism in ataxic
      patients.

PMID- 14600498
TI  - Dynamics of audio-visual interactions in the guinea pig brain: an
      electrophysiological study.
AB  - Audio-visual interactions and their specifications, evaluated by bioelectrical
      activities, in guinea pigs are presented in this study. The difference potential,
      as the evidence of an interaction, was calculated by subtracting the sum of
      averaged potentials recorded in visual and auditory events from the averaged
      potential recorded in an event where two stimuli combined in the same sweep.
      Dynamic investigations have shown an interaction when auditory stimulus is
      applied 24 ms before and 201 ms after visual stimulation. Latency between the
      difference potential and auditory stimulus was stable. Directional investigations
      have shown that the interaction is not observed when auditory and/or visual
      stimulation is used ipsilaterally, according to the recording side.

PMID- 14600499
TI  - Topical instillation of ciliary neurotrophic factor inhibits retinal degeneration
      in streptozotocin-induced diabetic rats.
AB  - Intraocular injections of ciliary neurotrophic factor (CNTF) or intraocular
      adenovirus-mediated CNTF gene transfer have been reported to inhibit retinal
      alterations in inherited retinal degeneration in mice strains. To investigate
      whether or not CNTF administered by eye drops prevents retinal degeneration in
      streptozotocin (STZ)-induced diabetic rats, recombinant CNTF was administered to
      eyes of diabetic rats (n=20) twice daily for 1 month after the onset of diabetes.
      The b-wave amplitude of electroretinogram in CNTF-administered diabetic rats was
      significantly larger than that of diabetic rats, and approached that of the
      controls. Atrophy of the inner plexiform layer, and cavity formation in the
      pigment epithelium, which were observed in diabetic rats, were prevented in CNTF
      administered diabetic rats. These results indicate that CNTF administration by
      eye drops prevents retinal degeneration in STZ-induced diabetic rats.

PMID- 14600500
TI  - Ca2+ and CaM kinase regulate neurofilament expression.
AB  - Cultured cerebellar granule neurons were used to examine the hypothesis that NMDA
      or KCl-dependent Ca2+ influx activates a signaling cascade mediating
      transcription, translation and assembly of neurofilaments. The data indicate that
      25 mM KCl and 140 microM NMDA induce neurofilament protein, mRNA, and assembly in
      neurites, and these require Ca2+ entry through voltage-sensitive Ca2+ channels or
      NMDA receptors, respectively. The CaM kinase and transcriptional inhibitors, KN
      62 and actinomycin D, respectively, attenuate the stimulatory effect of Ca2+.
      Granular neurons are a valuable model to explore the molecular basis for
      transcriptional regulation of neurofilament gene expression by neuronal activity.

PMID- 14600501
TI  - ATP secretion from nerve trunks and Schwann cells mediated by glutamate.
AB  - ATP release from rat sciatic nerves and from cultured Schwann cells isolated from
      the nerves was investigated using an online bioluminescence technique. ATP was
      released in relatively large amounts from rat sciatic nerve trunks during
      electrical stimulation. This release was blocked by the sodium channel inhibitor
      tetrodotoxin and the non-NMDA glutamate receptor blocker 6-cyano-7
      nitroquinoxaline-2,3-dione (CNQX). Schwann cells isolated from the nerve trunks
      did not release ATP when electrically stimulated but did in response to glutamate
      in a concentration-dependent manner. Glutamate-stimulated ATP release was
      inhibited by specific non-competitive AMPA receptor antagonist GYKI 52466 and
      competitive non-NMDA receptor antagonist CNQX. Glutamate-stimulated ATP release
      was decreased by inhibition of anion transporter inhibitors by furosemide, cystic
      fibrosis transmembrane conductance regulator by glibenclamide and exocytosis by
      botulinum toxin A, indicating that anion transporters and exocytosis provide the
      main secretion mechanisms for ATP release from the Schwann cells.

PMID- 14600502
TI  - Different effects of astrocytes and Schwann cells on regenerating retinal axons.
AB  - Following a crush injury of the optic nerve in adult rats, the axons of retinal
      ganglion cells, stimulated to regenerate by a lens injury and growing within the
      optic nerve, are associated predominantly with astrocytes: they remain of small
      diameter (0.1-0.5 microm) and unmyelinated for > or = 2 months after the
      operation. In contrast, when the optic nerve is cut and a segment of a peripheral
      nerve is grafted to the ocular stump of the optic nerve, the regenerating retinal
      axons are associated predominantly with Schwann cells: they are of larger
      diameter than in the previous experiment and include unmyelinated axons (0.2-2.5
      microm) and myelinated axons (mean diameter 2.3 microm). Thus, the grafted
      peripheral nerve, and presumably its Schwann cells, stimulate enlargement of the
      regenerating retinal axons leading to partial myelination, whereas the injured
      optic nerve itself, and presumably its astrocytes, does not. The result points to
      a marked difference of peripheral (Schwann cells) and central (astrocytes) glia
      in their effect on regenerating retinal axons.

PMID- 14600504
TI  - Impaired long-term potentiation in vivo in the dentate gyrus of pituitary
      adenylate cyclase-activating polypeptide (PACAP) or PACAP type 1 receptor-mutant
      mice.
AB  - The present study was conducted to clarify a role of pituitary adenylate cyclase
      activating polypeptide (PACAP) and PACAP type 1 receptor (PAC1R) in learning and
      memory function. We demonstrated long-term potentiation (LTP) in vivo in the
      dentate gyrus of PAC1R exon 2-deficient (PAC1R-/-) mice and heterozygous PACAP
      deficient (PACAP+/-) mice using extracellular recording techniques. We used two
      paradigms of tetanic stimulation, suprathreshold and at threshold tetanus, which
      both induced LTP in vivo in PAC1R-/- and PACAP+/- mice. However, the population
      spike of 'at threshold' but not 'suprathreshold' LTP decreased significantly in
      PAC1R-/- and PACAP+/- mice. At threshold LTP of PACAP+/- mice was impaired
      greater than the one of PAC1R-/- mice. Thus, both PACAP and PAC1R could
      contribute to the establishment of LTP in a gene dosage-dependent manner,
      although PACAP rather than PAC1R might play a pivotal role in learning and memory
      function.

PMID- 14600503
TI  - Ethanol attenuates ischemic and hypoxic injury in rat brain and cultured neurons.
AB  - Reactive oxygen species play a critical role in ischemic injury and oxidative
      stress induces apoptosis and triggers inflammation in neural cells. The effect of
      ethanol on ischemic brain injury was examined. Ethanol attenuated
      ischemia/reperfusion-induced brain infarction and elevation of inflammatory
      mediators, including tumor necrosis factor-alpha (TNF-alpha) expression,
      metalloproteinase-9, and neutrophil-associated myeloperoxidase activities. In
      cultured neurons, ethanol suppressed combined oxygen and glucose deprivation
      (COGD)/reoxygenation-induced oxidative stress and neuronal apoptosis.
      Furthermore, ethanol suppressed COGD/reoxygenation-induced activation of NF
      kappaB, a free-radical-sensitive regulator, leading to the attenuation of TNF
      alpha expression in glial cultures. We propose that scavenging of free radicals
      and attenuation of free-radical-induced alterations might account for ethanol's
      beneficial action against ischemic brain injury.

PMID- 14600505
TI  - Neurones treated with cyclo-oxygenase-1 inhibitors are resistant to amyloid-beta1
      42.
AB  - Epidemiological studies have shown that the risk of developing Alzheimer's
      disease is reduced by the chronic use of classical non-steroidal anti
      inflammatory drugs (NSAIDs), drugs that inhibit the cyclo-oxygenase (COX) enzymes
      that convert arachidonic acid to prostaglandins. In the present study, human SH
      SY5Y neuroblastoma cells or murine primary cortical neurones treated with NSAIDs
      were protected against the otherwise toxic effects of amyloid-beta1-42. COX-1
      selective inhibitors provided greater protection than did COX-2 selective
      inhibitors or lipoxygenase inhibitors, suggesting that activation of COX-1 is
      required for amyloid-beta1-42-induced neurotoxicity. Although the production of
      neuronal prostaglandin E2 in response to amyloid-beta1-42 was reduced by the
      presence of COX-1 inhibitors, no neurotoxic effects of prostaglandin E2, or any
      other prostaglandin, were observed.

PMID- 14600506
TI  - Adaptation to speaker's voice in right anterior temporal lobe.
AB  - Little is known on how voices are represented in the brain. We used fMRI to
      investigate whether parts of auditory cortex would be sensitive to the repetition
      of a speaker's voice. Subjects were scanned while passively listening to spoken
      syllables, presented in blocs in which either syllable or speaker were repeated.
      Only one cortical region, located in the anterior part of the right superior
      temporal sulcus (STS), responded differently to the two conditions: activation
      relative to the silent baseline was significantly reduced when syllables were
      spoken by a single voice than when they were spoken by different voices. This
      result suggest that the right anterior STS plays an important role in the
      representation of individual voices.

PMID- 14600507
TI  - Abnormal contingent negative variation in HIV patients receiving antiretroviral
      therapy.
AB  - The contingent negative variation, an event-related potential related to neural
      activity in the frontal lobe and basal ganglia, neuropsychological tests and
      structural MRI were used to examine CNS function and structure in HIV-positive
      patients receiving antiretroviral therapy. Relative to controls, HIV patients had
      smaller thalamic volume and reduced late contingent negative variation amplitude
      that correlated with caudal atrophy. Behaviorally, viremic patients were more
      impaired than virally suppressed patients and controls on neuropsychological
      measures of psychomotor speed, selective attention and mental flexibility. These
      results suggest that antiretroviral therapy may not be effective in protecting
      cortical and subcortical structures against HIV-related neuropathology,
      regardless of immune function. However, the benefits of antiretroviral therapy on
      immune function appear to facilitate neurocognitive performance.

PMID- 14600509
TI  - Test-retest reliability of auditory ERP components in healthy 6-year-old
      children.
AB  - One prerequisite of using auditory event-related brain potentials (ERP) in
      developmental and clinical research is to determine their reliability. We
      examined the individual stability and test-retest reliability of the ERP
      responses elicited by repetitive, slightly deviant, and novel sounds over 3
      months in healthy 6-year-old children. When broken down to 20 ms intervals, the
      standard-stimulus ERP responses shared > 77%, the deviant-stimulus responses 17
      31%, and the novel-stimulus responses > 33% of the individual variation over the
      two testing sessions; the mean amplitude differences (novel/deviant-standard) did
      not change significantly between sessions. The sufficiently high individual
      stability of the ERP responses support the utility of these measurements for
      studying the effects of novel sounds in this age group.

PMID- 14600508
TI  - The newborn human brain binds sound features together.
AB  - To process a stimulus as a holistic entity, the human brain must be able to
      conjoin its different features. Previous evidence suggests that this ability
      emerges during the first months of life, implying its considerable dependence on
      postnatal development. We recorded human newborn (1-3 days of age) electrical
      brain responses to frequently occurring (standard) sounds and to rarely occurring
      (deviant) sounds in a series. Responses to deviants differed from those to
      standards despite the fact that only the combination of sound frequency and
      intensity could be used as a cue for discriminating between these sound types.
      Our finding suggests that the human brain is ready for auditory feature binding
      very soon after birth.

PMID- 14600510
TI  - Dorsal, but not ventral, hippocampal lesions disrupt cocaine place conditioning.
AB  - The environment in which cocaine is experienced becomes associated with the
      effects of the drug and can then elicit cocaine craving. This study examined
      whether the hippocampus is involved in such associations using the conditioned
      place preference model. Rats received bilateral lesions of the dorsal or ventral
      hippocampus and were then conditioned to associate a particular environment with
      cocaine. Following conditioning, rats with lesions of the dorsal, but not
      ventral, hippocampus failed to demonstrate conditioned place preference for the
      cocaine-associated environment. These findings suggest that the dorsal
      hippocampus plays a role in the association of environmental stimuli with the
      effects of cocaine and may have important implications for understanding craving
      elicited by cocaine-conditioned stimuli.

PMID- 14600511
TI  - Monitoring of long-term toxicities of HIV treatments: an international
      perspective.

PMID- 14600512
TI  - Expanding access to HIV antiretroviral therapy among marginalized populations in
      the developed world.

PMID- 14600513
TI  - Increased association of 7SK snRNA with Tat cofactor P-TEFb following activation
      of peripheral blood lymphocytes.
AB  - OBJECTIVE: This study was undertaken to determine whether 7SK small nuclear RNA
      (snRNA), which has been proposed to function as an inhibitor of Tat cofactor P
      TEFb, plays a role in transcriptional latency in T cells. DESIGN AND METHODS: The
      association of 7SK snRNA with P-TEFb was investigated in resting and activated
      peripheral blood lymphocytes (PBLs). Primary PBLs were isolated by standard
      methods and activated with phytohemagglutinin (PHA). Levels of 7SK snRNA were
      determined by Northern blotting and levels of the P-TEFb subunits cyclin
      dependent kinase 9 and cyclin T1 were analyzed by immunoblotting. RESULTS: The
      association of 7SK snRNA with P-TEFb complexes was specific. Following activation
      of PBLs, the levels of 7SK snRNA increased in a manner similar to U1 and U6
      snRNA, sn RNAs involved in positive aspects of cellular gene expression.
      Unexpectedly, the association of 7SK snRNA with P-TEFb increased dramatically
      following lymphocyte activation. CONCLUSION: Increased association of 7SK snRNA
      with P-TEFb in activated lymphocytes correlates with increased global
      transcription. This suggests that 7SK snRNA is unlikely to promote
      transcriptional latency in lymphocytes through an association with P-TEFb; it
      also suggests that the proposal that the association of 7SK snRNA with P-TEFb
      acts to inhibit transcriptional elongation needs to be re-evaluated.

PMID- 14600514
TI  - Some HIV protease inhibitors alter lamin A/C maturation and stability, SREBP-1
      nuclear localization and adipocyte differentiation.
AB  - OBJECTIVES: To study whether HIV protease inhibitors could induce nuclear lamina
      alterations in adipocytes as observed in a genetic form of lipodystrophy due to
      lamin A/C mutation. DESIGN: We have previously observed that indinavir (IDV)
      impairs adipocyte differentiation and sterol regulatory element-binding protein-1
      (SREBP-1) nuclear localization in 3T3-F442A adipocytes. We compared here the
      effects of IDV with that produced by two other PIs, nelfinavir (NFV) and
      amprenavir (APV) on adipose conversion, cellular localization of SREBP-1, nuclear
      morphology, and maturation and stability of the lamina network. RESULTS: IDV and
      NFV, but not APV, altered adipose cell differentiation, as shown by lipid
      staining and protein expression of SREBP-1, CAAAT/enhancer binding protein
      (C/EBP)alpha and fatty acid synthase (FAS). In IDV-treated cells, 50-60 % of the
      nuclei could not accumulate SREBP-1. Twenty percent of these SREBP-negative
      nuclei were grossly dysmorphic, with blebs and prominent herniations, and showed
      an altered distribution of lamin A/C and lamin B. In IDV-treated cells, nuclear
      fragilization was shown by the abnormal extractibility of lamina proteins and
      SREBP-1, and the accumulation of prelamin A. NFV similarly altered lamin A/C
      maturation whereas APV was almost ineffective. CONCLUSIONS: We show in an adipose
      cell line that IDV and NFV induced alterations at the nuclear level by promoting
      defects in lamin A/C maturation, organization and stability. We suggest that
      these lamina network alterations might be responsible for SREBP-1 nuclear
      mislocalization therefore resulting in altered adipocyte differentiation.

PMID- 14600515
TI  - Cytomegalovirus-specific IFN-gamma production is associated with protection
      against cytomegalovirus reactivation in HIV-infected patients on highly active
      antiretroviral therapy.
AB  - OBJECTIVES: To identify the predictors of cytomegalovirus reactivation in AIDS
      patients on highly active antiretroviral therapy (HAART). DESIGN: This
      prospective study enrolled cytomegalovirus-seropositive AIDS patients on or about
      to start HAART, who were not receiving anti-cytomegalovirus prophylaxis. Clinical
      and laboratory data were collected over 3.5 years at clinic visits, which
      coincided with the study visits. METHODS: Blood was obtained at every study visit
      and was used for measurements of cytomegalovirus cell-mediated immunity
      (lymphocyte proliferation, IFN-gamma, IL-2, and IL-10 production),
      cytomegalovirus viral load, CD4 cell count, and HIV viral load. A logistic-normal
      model was used to analyse outcome data with repeated observations. RESULTS:
      Twenty-six patients had 40 episodes of cytomegalovirus reactivation (positive
      cytomegalovirus viral load) during the study. Their immunological and virological
      parameters were compared with 26 randomly selected control individuals from the
      same cohort. The risk of cytomegalovirus reactivation significantly decreased
      with every 6-month increase in HAART duration [odds ratio (OR) 0.5; P = 0.02] and
      marginally increased with every log10 RNA copies/ml HIV viral load (OR 2; P =
      0.07). CD4 cell counts, cytomegalovirus lymphocyte proliferation, IL-2, and IL-10
      did not reach significance as predictors of cytomegalovirus reactivation.
      However, cytomegalovirus IFN-gamma production significantly decreased the risk of
      cytomegalovirus reactivation (OR 0.03; P = 0.04). CONCLUSION: Cytomegalovirus
      specific IFN-gamma has a unique value as an immunological predictor of
      cytomegalovirus reactivation, demonstrating the importance of cellular immune
      responses in the control of cytomegalovirus replication in HAART recipients.

PMID- 14600516
TI  - Meta-analysis of randomized controlled trials of simplified versus continued
      protease inhibitor-based antiretroviral therapy in HIV-1-infected patients.
AB  - OBJECTIVE: To evaluate the efficacy and safety of simplified maintenance therapy
      (SMT) compared with continued protease inhibitor (PI) therapy. DESIGN: Meta
      analysis of nine randomized controlled trials in which 833 patients were switched
      to SMT (abacavir, efavirenz or nevirapine) and 616 continued PI, assessing
      virologic failure (primary outcome), discontinuation of therapy for reasons other
      than virologic failure, CD4 cell count, total plasma cholesterol and
      triglycerides. RESULTS: The risk ratio for virologic failure for SMT compared to
      continued PI was 1.06 [95% confidence interval (CI) 0.58-1.92; test for
      homogeneity P = 0.01] for SMT, 2.56, (95% CI, 1.17-5.64) for abacavir, 0.83 (95%
      CI, 0.36-1.91) for efavirenz and 0.54 (95% CI, 0.29-1.02) for nevirapine. The
      risk ratio for premature discontinuation of therapy with SMT was 0.61 (95% CI,
      0.48-0.77; test for homogeneity P < 0.10). The difference in absolute mean
      cholesterol for SMT compared to continued PI was -0.15 mmol/l, (95% CI, -0.40 to
      0.09; test for homogeneity P < 0.01) for SMT, -0.51 mmol/l (95% CI, -0.70 to 
      0.33) for abacavir, 0.22 mmol/l (95% CI, 0 to 0.43) for efavirenz and -0.19
      mmol/l (95% CI, -0.48 to 0.09) for nevirapine. CONCLUSIONS: Current evidence
      suggests that SMT with abacavir rather than continued PI increases the risk of
      virologic failure, this increased risk may be confined to patients with prior
      mono or dual therapy with reverse transcriptase inhibitors. There is not enough
      evidence on whether SMT with efavirenz and nevirapine influences the risk of
      virologic failure. SMT with any of the three drugs reduces the risk of
      discontinuation of therapy, and SMT with abacavir reduces plasma cholesterol.

PMID- 14600517
TI  - A randomized trial of the impact of multiple micronutrient supplementation on
      mortality among HIV-infected individuals living in Bangkok.
AB  - OBJECTIVES: To examine the impact of high-dose multiple micronutrient
      supplementation on survival and disease progression among HIV-infected
      individuals in Thailand. DESIGN: Randomized placebo-controlled trial. METHODS:
      Four-hundred and eighty-one HIV-infected men and women living in and around
      Bangkok with CD4 cell counts in the range 50 x 10(6)- 550 x 10(6)/l were
      randomized to receive micronutrients or placebo for a period of 48 weeks. Trial
      participants were examined clinically 12-weekly and tested for CD4 cell count 24
      weekly. A subset were tested for HIV plasma viral load at 48 weeks. RESULTS:
      Seventy-nine (16%) trial participants were lost to follow-up and 23 (5%) died.
      The death rate was lower in the micronutrients arm with the mortality hazard
      ratios [95% confidence interval (CI)] of 0.53 (0.22-1.25; P = 0.1) overall and
      0.37 (0.13-1.06; P = 0.052) and 0.26 (0.07-0.97; P = 0.03) among those with CD4
      cell counts < 200 x 10(6)/l and < 100 x 10(6)/l respectively. There was no impact
      on CD4 cell count or plasma viral load. CONCLUSIONS: Multiple micronutrient
      supplementation may enhance the survival of HIV-infected individuals with CD4
      cell counts < 200 x 10(6)/l. This could have important public health implications
      in the developing world where access to antiretrovirals remains poor. The
      clinical findings need to be reproduced in other settings and the mechanism,
      which appears to be independent of change in CD4 cell count, merits further
      investigation.

PMID- 14600519
TI  - Increased risk of myocardial infarction with duration of protease inhibitor
      therapy in HIV-infected men.
AB  - BACKGROUND: In the current context of dyslipidaema, hyperglycaema and
      lipodystrophia observed among HIV-seropositive subjects, it is important to study
      the risk of myocardial infarction (MI) in this population. The French Hospital
      Database on HIV, which includes a large number of seropositive subjects followed
      for substantial periods, offers the opportunity to analyse the impact of protease
      inhibitors (PI) on the risk of MI among men. METHODS: Cox model was used to study
      the risk factors of MI occurrence. Standardized morbidity ratios (SMR) in men
      exposed to PI were calculated with data from the French general male population
      (FGMP) of the same age as reference. RESULTS: Between 1996 and 1999, MI was
      diagnosed in 60 men among 88 029 person-years (PY), including 49 cases among men
      exposed to PI. In the Cox model, exposure to PI was associated with a higher risk
      of MI [relative hazard (RH), 2.56; 95% confidence interval (CI), 1.03-6.34]. The
      expected incidence in the FGMP was 10.8/10,000 PY. The SMR relative to the FGMP
      was 0.8 (95% CI, 0.5-1.3) for men exposed to PI for < 18 months (G1), 1.5 (95%
      CI, 0.8-2.5) for men exposed for 18-29 months (G2) and 2.9 (95% CI, 1.5-5.0) for
      men exposed for >or= 30 months (G3). With G1 as reference, the SMR was 1.9 (95%
      CI, 1.0-3.1) for G2 and 3.6 (95% CI, 1.8-6.2) for G3. CONCLUSION: Our results
      point to a duration-related effect relationship between PI and MI, with a higher
      MI incidence rate among men exposed to PI for 18 months or more.

PMID- 14600518
TI  - Polylactic acid implants (New-Fill) to correct facial lipoatrophy in HIV-infected
      patients: results of the open-label study VEGA.
AB  - BACKGROUND: In the absence of currently available therapy to manage facial
      lipoatrophy, strategies used to compensate for facial fat loss warrant clinical
      evaluation. METHODS: The goal of this open-label, single-arm, pilot study was to
      evaluate the efficacy and safety of facial injections of poly-L-lactic acid (PLA)
      (New-Fill) in HIV-infected patients with severe facial lipoatrophy. Patients
      received four sets of injection at day 0 and then every 2 weeks for 6 weeks.
      Patients were evaluated by clinical examination, facial ultrasonography, and
      photography at screening and at weeks 6, 24, 48, 72, and 96. RESULTS: Fifty
      patients were enrolled. At entry, the median facial fat thickness was equal to
      zero (range, 0.0-2.1 mm). The median total cutaneous thickness (TCT) increased
      significantly from baseline : +5.1 mm (range, 2.2-8.6 mm) at week 6, +6.4 mm
      (range, 3.1-9.1 mm) at week 24, +7.2 mm (range, 4.2-9.6 mm) at week 48, +7.2 mm
      (range, 3.5-9.6 mm) at week 72 and +6.8 mm (range, 3.9-10.1 mm) at week 96 (P <
      0.001). The proportion of patients with TCT > 10 mm was observed in 19% at week
      6, 41% at week 24, 61% at week 48, 52% at week 72 and 43% at week 96. In 22 (44%)
      patients, palpable but non-visible subcutaneous micronodules were observed with a
      spontaneous resolution in six patients at week 96. CONCLUSION: The benefit of PLA
      for the correction of the facial lipoatrophy in HIV-infected patients was clearly
      demonstrated, with an evident aesthetic and quality of life improvement. The
      efficacy, safety profile, and the simplicity of the injection schedule of PLA
      make this filling material a potentially attractive treatment.

PMID- 14600520
TI  - A randomized, double-blind, placebo-controlled trial of TMC125 as 7-day
      monotherapy in antiretroviral naive, HIV-1 infected subjects.
AB  - OBJECTIVE: To evaluate antiviral activity, tolerability, safety and
      pharmacokinetics of treatment with TMC125 (a non-nucleoside reverse transcriptase
      inhibitor), 900 mg twice daily for 7 days. DESIGN: Randomized, double-blind,
      placebo-controlled, phase IIA clinical trial. SETTING: Two hospital clinics in
      Moscow and St Petersburg, Russian Federation. PARTICIPANTS: Nineteen
      antiretroviral-naive, HIV-1-infected subjects. INTERVENTIONS: Randomization (2:1)
      was to twice daily treatment with either 900 mg TMC125 or matched placebo as
      monotherapy for 7 days. MAIN OUTCOME MEASURES: Change in plasma HIV-1 RNA from
      baseline values (primary); change in CD4 cell counts from baseline, and
      evaluation of safety, tolerability and pharmacokinetics of TMC125 treatment
      (secondary). RESULTS: A mean decrease from baseline in plasma HIV-1 RNA of 1.99
      log10 copies/ml and 0.06 log10 copies/ml was achieved after 7 days in the TMC125
      and placebo groups, respectively (P < 0.001). Plasma viral daily decay rates of
      0.33 log10 copies/ml and 0.02 log10 copies/ml were observed in the TMC125 and
      placebo groups, respectively (P < 0.001). A steady-state plasma concentration of
      TMC125 was attained within 5 days of treatment with a mean minimum concentration
      of 246 ng/ml and a mean maximum concentration of 419 ng/ml. The majority of
      subjects did not report any adverse events. No abnormalities consistent with
      changes in blood chemistry, haematology, urinalysis, electrocardiograph or vital
      signs were observed. CONCLUSIONS: TMC125 administered as monotherapy for 7 days
      yielded a 1.99 log10 copies/ml reduction in HIV-1 RNA in antiretroviral-naive,
      HIV-1-infected subjects. TMC125 was well tolerated and represents a promising and
      highly potent, next generation non-nucleoside reverse transcriptase inhibitor
      candidate.

PMID- 14600521
TI  - Safety and efficacy of switching to alternative nucleoside analogues following
      symptomatic hyperlactatemia and lactic acidosis.
AB  - OBJECTIVE: To evaluate the safety and efficacy of rechallenging patients who have
      recovered from nucleoside reverse transcriptase inhibitor (NRTI)-induced
      symptomatic hyperlactatemia or lactic acidosis with alternative NRTI-containing
      regimens. METHODS: Data in this case series was collected from patients followed
      at the UCSD Owen Clinic from July 1998 through September 2002. Cases of
      symptomatic hyperlactatemia were HIV-infected adults receiving NRTI who had
      symptoms compatible with hyperlactatemia and two lactates > 2 times the upper
      normal limit. Lactic acidosis was defined as lactate > 5 mmol/l with bicarbonate
      < 20 mmol/l. The suspected offending NRTI in the prior regimen were replaced with
      other NRTI thought to have equivalent antiviral potency but less mitochondrial
      toxicity. RESULTS: Ten patients diagnosed with symptomatic hyperlactatemia and
      two with lactic acidosis were later restarted on antiretrovirals that included
      new NRTI. The NRTI that patients were receiving when symptomatic hyperlactatemia
      or lactic acidosis was diagnosed included stavudine and lamivudine (n = 6),
      stavudine and didanosine (n = 4), and stavudine and abacavir (n = 2). The median
      (range) peak lactate was 5.4 (4.7-19.1) mmol/l. Five patients were rechallenged
      with abacavir and lamivudine, five with zidovudine, abacavir and lamivudine, and
      two with zidovudine and lamivudine. Among the 12 patients contributing over 22
      years of cumulative reexposure to NRTI-containing therapy, one developed
      symptomatic hyperlactatemia again yielding a recurrence rate of 45.5 cases/1000
      patient-years. Virologic control was maintained in all patients. CONCLUSIONS:
      This data supports the strategy that in cases of symptomatic hyperlactatemia or
      lactic acidosis in which the toxicity is associated with stavudine, didanosine or
      both, it is safe and efficacious to reintroduce NRTI that are less potent
      inhibitors of mitochondria.

PMID- 14600522
TI  - Tuberculosis epidemics driven by HIV: is prevention better than cure?
AB  - OBJECTIVE: To compare the benefits of tuberculosis (TB) treatment with TB and HIV
      prevention for the control of TB in regions with high HIV prevalence. DESIGN AND
      METHODS: A compartmental difference equation model of TB and HIV has been
      developed and fitted to time series and other published data using Bayesian
      methods. The model is used to compare the effectiveness of TB chemotherapy with
      three strategies for prevention: highly active antiretroviral therapy (HAART),
      the treatment of latent TB infection (TLTI) and the reduction of HIV
      transmission. RESULTS: Even where the prevalence of HIV infection is high,
      finding and curing active TB is the most effective way to minimize the number of
      TB cases and deaths over the next 10 years. HAART can be as effective, but only
      with very high levels of coverage and compliance. TLTI is comparatively
      ineffective over all time scales. Reducing HIV incidence is relatively
      ineffective in preventing TB and TB deaths over 10 years but is much more
      effective over 20 years. CONCLUSIONS: In countries where the spread of HIV has
      led to a substantial increase in the incidence of TB, TB control programmes
      should maintain a strong emphasis on the treatment of active TB. To ensure
      effective control of TB in the longer term, methods of TB prevention should be
      carried out in addition to, but not as a substitute for, treating active cases.

PMID- 14600523
TI  - Estimation of AIDS adult mortality by verbal autopsy in rural Malawi.
AB  - OBJECTIVE: To estimate AIDS-related adult mortality using verbal autopsies (VA)
      in a rural sub-Saharan African setting with high HIV prevalence. DESIGN: VA data
      were collected from relatives and neighbors that described the circumstances
      leading to death for 92 adults in three rural areas of Malawi. These adults were
      initially interviewed in 1998 as part of a longitudinal social survey of a sample
      of 1554 women and 1126 men, and their deaths occurred between then and a 3-year
      follow-up interview in 2001. METHODS: AIDS-related deaths were identified using a
      standard World Health Organization (WHO) algorithm and this observed number of
      deaths was compared with the expected number. The expected number is derived from
      a comparison of adult mortality in this sample with the pre-AIDS mortality levels
      measured in the 1987 Malawi census, giving an 'excess mortality factor' that can
      be considered to be AIDS related. It was calculated that 74.9% of observed deaths
      in 1998-2001 would be from AIDS. RESULTS: According to the WHO algorithm, 75.5%
      of the VA deaths could be categorized as AIDS deaths. The gender-specific figures
      were 75.1% for females and 76.3% for males. CONCLUSIONS: Results are consistent
      with those found in studies conducted in other areas of sub-Saharan Africa at
      earlier stages in the epidemic. They confirm that VA data can be used to estimate
      with a reasonable degree of confidence the distribution of AIDS- and non-AIDS
      related deaths in the aggregate, even in a rural population with relatively low
      levels of education.

PMID- 14600524
TI  - HIV-1 subtype B' dictates the AIDS epidemic among paid blood donors in the Henan
      and Hubei provinces of China.
AB  - OBJECTIVE: To investigate the genetic background of HIV-1 strains among infected
      paid blood donors (PBD) in the Henan and Hubei provinces of China. METHODS: The
      polymerase chain reaction was used to amplify HIV-1 gag p17 fragments and some 5'
      half or full-length viral genomes from peripheral blood mononuclear cells. The
      HIV-1 sequences obtained were analysed using phylogenetic and recombinant
      approaches. RESULTS: Among the total of 62 samples studied, 59 (95.2%) came from
      PBD. Of those 59 PBD, 45 were collected from 14 different geographical locations
      in Henan, whereas the remaining 14 were from five locations in Hubei. A total of
      62 HIV-1 gag p17 fragments, three 5'-half and one full HIV-1 genome sequences
      were obtained. Phylogenetic analysis of these sequences suggests that PBD from
      Henan and Hubei, despite being geographically distant, harbored a group of
      genetically closely related HIV-1 B' strains. No recombinant forms have been
      detected in this cohort. CONCLUSION: Our data indicate that the AIDS epidemic
      among PBD in Henan and Hubei is caused largely by HIV-1 subtype B', which
      contrasts greatly with the CB' recombinant strains CRF-07 and CRF-08 currently
      dominating among the drug abusers in other regions of China. Our report has
      revealed the first complete genome background of the most dominant circulating
      HIV-1 strain in Henan and Hubei, which is essential for the design and
      development of an effective AIDS vaccine for the region.

PMID- 14600525
TI  - Diverse HIV-1 subtypes and clinical, laboratory and behavioral factors in a
      recently infected US military cohort.
AB  - OBJECTIVE: To describe the demographics, risk behaviors, and HIV-1 subtypes in a
      large cohort of recently HIV-infected military personnel. DESIGN: Descriptive,
      cross-sectional study. METHODS: US military personnel with recent HIV
      seroconversion from six medical referral centers were enrolled with a self
      administered questionnaire, CD4 cell counts, syphilis and hepatitis B serologies,
      plasma viral RNA levels, and HIV-1 subtype nucleic acid sequencing. RESULTS:
      Between February 1997 and May 2000, 520 patients were enrolled. Most [488
      (94.3%)] were infected with HIV-1 subtype B. The most prevalent non-B subtype was
      a circulating recombinant form (CRF01_AE) [17 (61%)]; however, two pure subtypes
      (C and D), as well as CRF02_AG, CRF09_cpx and a BE recombinant were identified.
      The likely area of HIV-1 acquisition was the United States for 70% of the
      volunteers. At least three non-B subtype infections (two subtype C, one subtype
      CRF01_AE) were apparently acquired domestically. Risk behaviors and comorbid
      sexually transmitted diseases were reported during the seroconversion period.
      Volunteers with non-B subtype HIV infection were more likely to report
      heterosexual contacts [92% vs. 39%; odds ratio (OR), 10.0], including contacts
      with commercial sex workers (41% vs. 13%; OR, 4.9). The Roche Amplicor version
      1.0 assay was less sensitive for non-B subtype infections than the Roche Amplicor
      version 1.5 assay. CONCLUSION: There is a high prevalence and diversity of non-B
      HIV subtypes in this large cohort. Efficient diagnosis of acute primary HIV-1
      infection was identified as a goal for prevention programs. Modifiable risk
      behaviors and target populations for intervention were identified.

PMID- 14600526
TI  - How bad is HAART for the HEART?

PMID- 14600527
TI  - Polylactic acid implants. A new smile for lipoatrophic faces?

PMID- 14600528
TI  - In vitro infection of human primary adipose cells with HIV-1: a reassessment.
AB  - We reassessed the infection ability of human primary preadipocytes. The use of
      X4, R5 or VSV-G-pseudotyped viral particles indicated that viral entry is the
      limiting step. However, transfection with HIV-1 receptors restored efficient
      infection. Analyses of CD4, CXCR4 and CCR5 expression on preadipocytes and
      adipocytes revealed that receptor co-expression levels did not permit HIV-1 entry
      into adipose cells from all biopsies tested. We concluded that adipose tissue
      cannot be infected with HIV-1 in vivo.

PMID- 14600529
TI  - The effects of placental malaria on mother-to-child HIV transmission in Rakai,
      Uganda.
AB  - We examined the association of placental malaria and mother-to-child transmission
      (MTCT) of HIV in a prospective community-randomized trial in Rakai District,
      Uganda. In the 746 HIV-positive mother-infant pairs, the MTCT rate was 20.4%.
      Placental malaria was more common in HIV-positive than HIV-negative women. After
      multivariate adjustment for HIV viral load, the risk of MTCT associated with
      placental malaria was 2.89 and with HIV viral load the risk was 2.85.
      Interventions to prevent malaria during pregnancy could potentially reduce MTCT.

PMID- 14600530
TI  - Acute tubular necrosis in a patient receiving tenofovir.

PMID- 14600531
TI  - Efavirenz-containing highly active antiretroviral therapy in an HIV-infected
      patient with myasthenia gravis.

PMID- 14600532
TI  - Breastfeeding and HIV transmission.

PMID- 14600533
TI  - Caregivers' beliefs regarding pain in children with cognitive impairment:
      relation between pain sensation and reaction increases with severity of
      impairment.
AB  - OBJECTIVES: To determine whether caregivers of children with cognitive impairment
      (CI) have systematic beliefs regarding the pain of this special group of children
      and whether these beliefs are related to their general attitudes towards people
      with mental challenges, or their experience with, or knowledge about, children
      with CI . PARTICIPANTS: Sixty-five caregivers (52 parents and 13 health care
      providers) of children with significant CI. MEASURES: Caregivers completed the
      Mental Retardation Attitude Inventory-Revised and provided information regarding
      their previous experience and learning about children with CI. They also
      completed the Pain Opinion Questionnaire, indicating the percentage of children
      with mild, moderate, or severe/profound CI that they believe experience 5 facets
      of pain "less than", "the same as", or "more than" children without CI:
      sensation, emotional reaction, behavioral reaction, communication, and frequency.
      RESULTS: Caregivers believed children's pain Sensation becomes greater, relative
      to children without CI, as severity of CI increases and that pain reaction is
      most consistent with pain sensation for children with severe CI. They also
      believed children with mild CI may over-react to pain. Caregivers' beliefs
      regarding pain were not influenced by their general attitudes about people with
      mental challenges or by their experience with children with CI, but those with
      more learning regarding children with CI believed that they experience pain less
      than children without CI. CONCLUSIONS: Caregivers have a priori beliefs regarding
      pain in children with CI that vary with level of cognitive impairment and pain
      facet. These beliefs could impact children's care.

PMID- 14600534
TI  - Questionnaire validation: a brief guide for readers of the research literature.
AB  - Because of the importance of pain assessment to understanding the nature and
      scope of pain problems, and for testing the efficacy of pain treatments, new pain
      measures are frequently developed. Research that describes the development and
      evaluation of pain measures should include detailed information concerning the
      validity and reliability of the measures. However, for the findings from this
      research to be most useful, the consumers of this research (clinicians and
      researchers who use pain measures) should understand the concepts of validity and
      reliability, and the procedures used for evaluating these in pain assessment
      research. The purpose of this commentary is to provide a summary of these
      psychometric issues, using the study and findings of Krause and Backonja as an
      illustrative example of the concepts.

PMID- 14600535
TI  - Neonatal Facial Coding System for assessing postoperative pain in infants: item
      reduction is valid and feasible.
AB  - OBJECTIVE: The objectives of this study were to: (1). evaluate the validity of
      the Neonatal Facial Coding System (NFCS) for assessment of postoperative pain and
      (2). explore whether the number of NFCS facial actions could be reduced for
      assessing postoperative pain. DESIGN: Prospective, observational study. PATIENTS:
      Thirty-seven children (0-18 months old) undergoing major abdominal or thoracic
      surgery. OUTCOME MEASURES: The outcome measures were the NFCS, COMFORT "behavior"
      scale, and a Visual Analog Scale (VAS), as well as heart rate, blood pressure,
      and catecholamine and morphine plasma concentrations. At 3-hour intervals during
      the first 24 hours after surgery, nurses recorded the children's heart rates and
      blood pressures and assigned COMFORT "behavior" and VAS scores. Simultaneously we
      videotaped the children's faces for NFCS coding. Plasma concentrations of
      catecholamine, morphine, and its metabolite M6G were determined just after
      surgery, and at 6, 12, and 24 hours postoperatively. RESULTS: All 10 NFCS items
      were combined into a single index of pain. This index was significantly
      associated with COMFORT "behavior" and VAS scores, and with heart rate and blood
      pressure, but not with catecholamine, morphine, or M6G plasma concentrations.
      Multidimensional scaling revealed that brow bulge, eye squeeze, nasolabial
      furrow, horizontal mouth stretch, and taut tongue could be combined into a
      reduced measure of pain. The remaining items were not interrelated. This reduced
      NFCS measure was also significantly associated with COMFORT "behavior" and VAS
      scores, and with heart rate and blood pressure, but not with the catecholamine,
      morphine, or M6G plasma concentrations. CONCLUSION: This study demonstrates that
      the NFCS is a reliable, feasible, and valid tool for assessing postoperative
      pain. The reduction of the NFCS to 5 items increases the specificity for pain
      assessment without reducing the sensitivity and validity for detecting changes in
      pain.

PMID- 14600536
TI  - Acupuncture in the management of chronic low back pain: a blinded randomized
      controlled trial.
AB  - OBJECTIVE: To assess the efficacy of acupuncture in the treatment of chronic low
      back pain. METHODS: Patients (n = 60) with chronic low back pain were recruited
      and randomly allocated to either Acupuncture therapy or Placebo transcutaneous
      electrical nerve stimulation (TENS) groups. Patients were treated weekly for 6
      weeks, and blinded assessments were carried out pre- and post-treatment using the
      McGill Pain Questionnaire (MPQ) and visual analog scales (VAS) for pain, the
      Short-form 36 quality-of-life questionnaire, and a simple range of motion
      measurement. A total of 46 patients completed the trial and were followed up at 6
      months. RESULTS: Analysis of results using t tests showed that in both groups
      there were significant pre-post improvements for all scores, except for MPQ
      scores in the Placebo-TENS group. There was no significant difference between the
      2 groups for any of the outcome measures at the end of treatment. Results from
      the 6-month follow-up would suggest that the response was better in the
      acupuncture group. DISCUSSION: Further research is necessary to fully assess the
      efficacy of this treatment in combating chronic low back pain using larger sample
      sizes or alternative control groups.

PMID- 14600537
TI  - Spinal cord stimulation for complex regional pain syndrome: an evidence-based
      medicine review of the literature.
AB  - OBJECTIVES: The purpose of this investigation is to assess the evidence for
      efficacy of SCS in the management of pain in patients with CRPS. METHODS:  SEARCH
      STRATEGY: Electronic databases such as Medline and Cochrane Library were queried
      using key words such as "spinal cord stimulation," "reflex sympathetic dystrophy
      (RSD)," and "complex regional pain syndrome (CRPS)." SELECTION CRITERIA: Relevant
      published randomized controlled trials (RCT), cohort studies, case-control
      studies, case series, and case reports that described SCS as the primary
      treatment modality for patients with CRPS were eligible for inclusion. DATA
      COLLECTION AND ANALYSIS: Data extracted from qualified studies were summarized in
      sections of methodology, demographics, SCS equipment, primary and secondary
      outcomes, and complications. RESULTS: Thirteen studies using the primary search
      strategy and 7 studies from their reference lists were considered. Five of these
      20 studies were discarded. One RCT, 2 prospective observational, and 12
      retrospective observational studies were eventually considered. The
      methodological quality of all studies was poor except for the single RCT study.
      DISCUSSION: Although limited in quality and quantity, available evidence from the
      examined literature suggests that SCS is effective in the management of pain in
      patients with CRPS (grade B/C). Clinically useful information extracted from the
      available studies is very limited in guiding clinicians in the rational use of
      SCS for pain management in CRPS patients. Future attempts to investigate the
      efficacy of SCS in CRPS patients should involve methodologically robust designs
      such as randomized studies that have sufficient power.

PMID- 14600538
TI  - What's to be done? Comments on Grabow et al.

PMID- 14600539
TI  - ACSM: biomechanics of movement and performance.

PMID- 14600540
TI  - Serial assessment of peak VO2 and VO2 kinetics early after heart transplantation.
AB  - PURPOSE: Serial evaluation of aerobic metabolism and exercise tolerance early
      after heart transplantation (HT). METHODS: Fifteen heart transplant recipients
      (HTR), aged 52.0 +/- 9.9 yr (mean +/- SD), not undergoing structured
      rehabilitation programs, were tested two to four times during the first 2 yr post
      HT. As a reference, a group of 11 healthy untrained controls (C) was utilized.
      Peak heart rate (peak HR), peak O2 uptake (peak VO2), and ventilatory threshold
      (VT) were determined during incremental bicycle exercise to voluntary exhaustion.
      VO2 kinetics were evaluated during constant-load exercise below VT, with
      determination of the duration of the "cardiodynamic" component (TDp) and of the
      time constant of the "primary" component (taup). RESULTS: Peak VO2 (L.min-1) was
      positively related to months post-HT (y=1.17 + 0.02x, P=0.003), and it increased
      by approximately 30% during the investigated period, although values in HTR were
      lower than in C (2.19 +/- 0.24). Peak HR was lower in HTR (136 +/- 15 beats.min
      1) than in C (168 +/- 5), and it was not related to time post-HT. TDp was longer
      in HTR (31.4 +/- 6.3 s) than in C (23.2 +/- 6.1), and it was not related to time
      post-HT. A subgroup of HTR with markedly longer taup during the first months post
      HT showed a significant decrease of this parameter as a function of time post-HT.
      CONCLUSIONS: Aerobic metabolism is impaired in HTR. Both central (cardiovascular)
      and peripheral (skeletal muscle) factors contribute to the reduced exercise
      tolerance. HTR showed, during the first 2 yr post-HT, a significant increase in
      peak VO2 and (in the patients with the slowest VO2 kinetics during the first
      months after HT) a significant improvement of the VO2 kinetics. The main gains
      seem to occur at the peripheral level.

PMID- 14600541
TI  - Effects of lidocaine into knee on QF strength and EMG in patients with ACL
      lesion.
AB  - PURPOSE: In our previous study, we found that injection of lidocaine into intact
      knees reduced the maximal voluntary contraction (MVC) and integrated
      electromyogram (I-EMG) of the quadriceps femoris (QF). This study was designed to
      investigate changes in the MVC and I-EMG of the QF in response to lidocaine, in
      patients with anterior cruciate ligament (ACL) lesion, to evaluate alpha
      motoneuron activity innervating the QF. METHODS: The MVC of knee extension and I
      EMG of the vastus medialis (VM), vastus lateralis (VL), and rectus femoris (RF)
      muscles were measured in eight patients with ruptured ACL, before and after
      lidocaine injection into the knee. RESULTS: There were no significant differences
      between preinjection and postinjection values of MVC (preinjection: 167 +/- 49
      N.m; postinjection: 164 +/- 55 N.m) and I-EMG (preinjection: VL: 0.11 +/- 0.06,
      VM: 0.13 +/- 0.10, RF: 0.09 +/- 0.04) (postinjection: VL: 0.12 +/- 0.07, VM: 0.13
      +/- 0.10, RF: 0.09 +/- 0.05). CONCLUSION: Our results indicated that hindrance of
      afferent feedback from the knee in patients with ACL rupture did not
      significantly change alpha-motoneuron activity. Lidocaine injection into the knee
      joint of the subjects in this study only attenuated afferent feedback from
      mechanoreceptors in the knee joint cavity, but not in the ACL, as afferent
      feedback from ACL was already lost due to ACL rupture. This indicated that
      attenuation of afferent feedback from mechanoreceptors in the knee joint cavity
      other than the ACL did not significantly decrease the activity of alpha
      motoneurons innervating the QF during MVC exertion. Therefore, our findings
      provide evidence that afferent feedback from the ACL has a major influence on the
      MVC exertion of the QF.

PMID- 14600543
TI  - Physical activity and the common cold in men administered vitamin E and beta
      carotene.
AB  - BACKGROUND AND PURPOSE: It has been proposed that moderate regular aerobic
      training may enhance immunocompetence, whereas excessive training may cause
      immunosuppression. We evaluated whether physical activity at work, or at leisure,
      is associated with the risk of the common cold, and whether the antioxidants
      vitamin E and beta-carotene affect common cold risk in physically active people.
      METHODS: A cohort of 14,401 men aged 50-69 yr and working at study entry was
      drawn from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study,
      which examined the effect of vitamin E, 50 mg.d(-1), and beta-carotene, 20 mg.d(
      1), on lung cancer in smokers using a 2 x 2 factorial design. The trial was
      conducted in southwestern Finland in 1985-1993; the intervention lasted for 6.1
      yr (median). Physical activity at work, and the type and frequency of leisure
      time exercise were recorded at study entry. The subjects were questioned about
      common cold episodes 3x yr-1. We modeled the cumulative incidence of colds during
      a 2-yr follow-up period with Poisson regression, adjusting for potential
      confounders. RESULTS: Physical activity at work and at leisure had no association
      with common cold risk. In subjects with physically load-bearing jobs, neither
      vitamin E nor beta-carotene affected significantly the risk of common cold. In
      subjects carrying out heavy exercise at leisure, vitamin E and beta-carotene
      increased the risk of colds when compared with placebo. CONCLUSIONS: Contrary to
      previous suggestions, moderate physical activity is not associated with lower
      risk of common cold in middle-aged male smokers. It has been previously proposed
      that antioxidant supplementation might be beneficial for subjects carrying out
      heavy exercise, but in our study vitamin E and beta-carotene increased the risk
      of colds in subjects carrying out heavy exercise at leisure.

PMID- 14600542
TI  - The epidemiology and clinical analysis of several outbreaks of herpes
      gladiatorum.
AB  - PURPOSE The purpose of this analysis was to determine whether present National
      Federation of State High School Associations (NFHS) guidelines adequately prevent
      and control outbreaks of primary herpes gladiatorum (HG) in high-school
      wrestlers. METHODS: Using telephone interviews, direct physical examinations, and
      review of medical charts, data were collected on HG outbreaks among participating
      teams in the 1999 Minnesota State High School League (MSHSL) wrestling season and
      on HG outbreaks for 3 yr at a 28-d summer wrestling camp. RESULTS: The outbreak
      during the 1999 MSHSL wrestling season involved 61 wrestlers and three coaches on
      19 teams over 42 d, with a 32.7% probability of transmission to sparring
      partners. Typical length of time from exposure to outbreak varied from 4 to 11 d
      with an average of 6.80 +/- 1.70 d. Analysis of data from three outbreaks at a 28
      d wrestling camp showed that most outbreaks (96%) occurred on the ventral surface
      of the body, with 71.9% on the head, face, and neck, areas in direct contact when
      wrestlers are engaged in the lock-up position. Analysis of data from the 2001
      camp outbreak showed that the locations of the lesions reflected the handedness
      of the wrestler. CONCLUSION: The NFHS guidelines are inadequate to prevent and
      control outbreaks of HG. The focus of preventive efforts needs to change from mat
      cleanliness to more rapid detection of outbreaks by requiring culture results and
      appropriate therapy for all suspected bacterial and herpes lesions before
      allowing return to contact. To minimize and control spread of HG, treatment and
      isolation should be implemented based not only on vesicle formation but also on
      systemic signs and symptoms.

PMID- 14600544
TI  - Physical activity, exercise, and cancer: prevention to treatment--symposium
      overview.

PMID- 14600545
TI  - Physical activity and cancer prevention--data from epidemiologic studies.
AB  - PURPOSE: The aim of this paper is to examine whether physical activity plays any
      role in the prevention of cancer. METHODS: To accomplish this, data from
      published epidemiologic studies on the relation between physical activity and the
      risk of developing cancer were reviewed. RESULTS: The data are clear in showing
      that physically active men and women have about a 30-40% reduction in the risk of
      developing colon cancer, compared with inactive persons. Although the data are
      sparse, it appears that 30-60 min.d(-1) of moderate- to vigorous-intensity
      physical activity is needed to decrease risk. There is a dose-response relation,
      with risk declining further at higher levels of physical activity. It is also
      clear that physical activity is not associated with the risk of developing rectal
      cancer. With regard to breast cancer, there is reasonably clear evidence that
      physically active women have about a 20-30% reduction in risk, compared with
      inactive women. It also appears that 30-60 min.d(-1) of moderate- to vigorous
      intensity physical activity is needed to decrease the risk of breast cancer, and
      that there is likely a dose-response relation. For prostate cancer, the data are
      inconsistent regarding whether physical activity plays any role in the prevention
      of this cancer. There are relatively few studies on physical activity and lung
      cancer prevention. The available data suggest that physically active individuals
      have a lower risk of lung cancer; however, it is difficult to completely account
      for cigarette smoking. There is little information on the role of physical
      activity in preventing other cancers. CONCLUSION: Physical activity is associated
      with lower risk of developing certain site-specific cancers, in particular colon
      and breast cancers.

PMID- 14600546
TI  - Physical activity and cancer prevention: animal-tumor models.
AB  - PURPOSE: The aims of this paper are to briefly review the types of animal and
      tumor models used in carcinogenesis studies and to consider their utility in
      studies of physical activity and cancer. METHODS: Published data from animal
      studies using tumor models for which corresponding human epidemiologic evidence
      shows a clear association between physical activity and that cancer (i.e., colon
      and breast) are reviewed. RESULTS: A variety of animal-tumor models have been
      used in cancer studies including spontaneous tumors, chemically induced tumors,
      orthotopic and syngeneic tumor transplantation, injected tumors, and genetically
      engineered (transgenic, knockout, and mutation-induced) mice with a
      predisposition to neoplasia. The most commonly used animal-tumor model in the
      study of physical activity has been the chemical carcinogenesis model.
      Methodological limitations of the various animal-tumor models are described
      including variations in dosing, route of administration, and type of carcinogen
      used, and forced versus voluntary exercise effects. CONCLUSIONS: Animal-tumor
      models are useful for understanding specific aspects of the carcinogenesis
      process and the interaction of this process with exercise. There is no one animal
      tumor model that is ideally suited for studying physical activity interventions.
      However, animal-tumor models can be viewed as complementary to epidemiologic
      studies and human clinical trials in the area of physical activity and cancer
      prevention.

PMID- 14600547
TI  - Physical activity and cancer prevention--mechanisms.
AB  - PURPOSE: This paper presents potential mechanisms by which exercise or physical
      activity may affect cancer development. METHODS: Analysis of published and
      unpublished experimental and epidemiological data from the cancer-activity
      literature and from other fields of study are compiled to provide a summary of
      potential mechanisms by which exercise may mediate cancer development. RESULTS:
      Exercise appears to have a beneficial effect relative to cancer development, and
      the reader is referred to other sections of this symposium. To date however, the
      mechanism(s) remains unknown. Potential mechanisms influenced by exercise include
      alterations in steroid hormones or insulin/insulin-like growth factors, immune
      modulation, alterations in free radical generation, changes in body composition
      or weight, and direct effects on the tumor. Cancer is a complex process. It is
      clear that multiple mechanisms may be operative and that the characteristics of
      the individual, type of exercise, as well as type of cancer and stage of
      carcinogenesis will affect which mechanisms may affect the disease. More
      experimental research in both animal models and in human clinical studies is
      needed to understand the basic biological mechanisms underlying the effect of
      physical activity on cancer. CONCLUSION: In general, physical activity is
      associated with reduced risk of cancer development, yet to date, the mechanisms
      remain unknown.

PMID- 14600548
TI  - Intervention studies in exercise and cancer prevention.
AB  - PURPOSE: The aim of this article is to examine the role of exercise randomized
      clinical trials and other intervention studies in defining the associations
      between physical activity and cancer prevention. METHODS: To accomplish this,
      data from published randomized clinical trials and other intervention studies
      were reviewed and summarized. RESULTS: There are few intervention studies that
      specifically assess the effect of exercise on biomarkers for cancer. Some early
      work looking at exercise effect on endogenous sex hormones in premenopausal women
      is relevant to the etiology of several cancers including breast and endometrium,
      as risk of these cancers is increased in women with high levels of circulating
      estrogens. Several randomized clinical trials have assessed the effect of
      exercise on insulin, a potential cancer growth promoter. A smaller number of
      studies have assessed the impact of exercise interventions on insulin-like growth
      factor and insulin-like growth factor binding protein. Several small intervention
      trials have studied the effect of exercise on immune function. Two current
      randomized clinical trials focused on exercise effects on cancer biomarkers are
      outlined. CONCLUSION: Randomized clinical trials provide important information
      about the effect of exercise interventions on cancer biomarkers and other
      outcomes relevant to cancer.

PMID- 14600549
TI  - Exercise in cancer survivors: an overview of research.
AB  - PURPOSE: To provide an overview of research that has examined exercise in cancer
      survivors including recently completed trials at the University of Alberta.
      METHODS: A search of published studies using electronic data bases and previous
      review articles. The review is divided into breast and nonbreast cancers, during
      and after treatment, and trials from the University of Alberta. RESULTS: Forty
      seven published studies were located and summarized plus four trials from the
      University of Alberta. Almost all studies showed beneficial effects of exercise
      in breast and nonbreast cancer groups alike as well as during and after cancer
      treatment. CONCLUSION: Preliminary research suggests that exercise may be an
      effective intervention for enhancing quality of life (QOL) in cancer survivors.
      The effects of exercise on biomarkers, cancer recurrence, other diseases, and
      overall survival are unknown. Future research is needed to extend our knowledge
      beyond breast cancer survivors, conduct second generation studies in breast
      cancer survivors, examine mechanisms for changes in QOL, compare exercise with
      other QOL interventions, and examine biomarkers, cancer recurrence, and survival.

PMID- 14600551
TI  - Plasma malondialdehyde increases transiently after ischemic forearm exercise.
AB  - Exercise and ischemia-reperfusion (I-R) have previously been shown to induce
      oxidative stress in skeletal muscle. Previous studies have demonstrated
      conflicting results when exercise-induced oxidative stress has been measured
      using plasma carbonyls, specifically malondialdehyde (MDA). These conflicting
      results likely stem from the timing and method utilized to measure plasma
      carbonyls. PURPOSE: To determine the concentration and timing of aldehyde and
      ketone generation after ischemic forearm exercise utilizing HPLC analysis.
      METHODS: Plasma carbonyls, including MDA, 17-beta-estradiol, and lactate, were
      measured after a forearm ischemic exercise test (FIT) in males and females (in
      both phases of their menstrual cycle). Blood flow was occluded to the forearm,
      and six cycles of maximal isometric handgrip exercise were executed using a 9:1,
      duty:rest cycle, for 60 s. Blood samples were collected pre, immediately post,
      and 1, 3, and 10 min post-FIT. RESULTS: Plasma MDA increased similarly for both
      males and females immediately post and 1 min post-FIT (P<0.05) and returned to
      baseline levels by 3 min post-FIT. Ischemic exercise did not alter plasma
      concentrations of other measured carbonyls, and gender and menstrual cycle did
      not influence any measured variable (P>0.05), except for lactate concentrations,
      which increased more for males (P<0.05). Force was higher for males at all time
      points (P<0.05); however, there was no effect of gender on percent fatigue.
      CONCLUSIONS: Future studies must consider sampling times after metabolic stress
      in order to quantify changes in MDA concentration.

PMID- 14600550
TI  - Effects of short-term exercise training on plasminogen activator inhibitor (PAI
      1).
AB  - PURPOSE: To observe the effects of exercise training on plasminogen activator
      inhibitor, type-1 (PAI-1), tissue plasminogen activator (tPA), and associated
      metabolic variables in sedentary men and women. METHODS: A randomized, controlled
      experimental design was used to examine the influence of 10 d of moderate
      intensity exercise training on measures of fibrinolysis. Sixteen men and 16 women
      between the ages of 50 and 70 yr were randomly assigned to exercise (EX) and
      control groups (CON) that were balanced for gender and hormone replacement
      therapy. Blood samples were collected on days 1, 2, 11, and 12 for measurement of
      plasma PAI-1, tPA, insulin, glucose, and triglyceride. Subjects in EX performed
      50 min of treadmill walking at an intensity corresponding to 65% of heart rate
      reserve each day for 10 consecutive days. RESULTS: There were no significant
      changes in PAI-1, tPA, or associated metabolic variables between EX and CON
      during the intervention period. Within EX subjects, those with higher body
      fatness had a significant decrease in insulin and triglyceride compared with
      those with lower body fatness. However, no changes in fibrinolytic measures were
      observed within these subgroups. CONCLUSIONS: Short-term exercise training does
      not change PAI-1 levels in normal, asymptomatic men and women. In addition,
      modest decreases in insulin and triglyceride in individuals with elevated body
      fatness do not result in changes in PAI-1 after short-term training. It appears
      likely that decreases in PAI-1 with exercise training require decreases in
      adiposity and/or marked changes in metabolic variables.

PMID- 14600552
TI  - Pulmonary hemodynamics during a strenuous intermittent exercise in healthy
      subjects.
AB  - PURPOSE: It has been suggested that an intermittent work exercise test (IWET) is
      as efficient but better tolerated than continuous exercise for rehabilitation.
      Although systemic and pulmonary cardiovascular adjustments have been investigated
      for continuous exercise, it has not been done for IWET with exercise bouts near
      maximal work rate. METHODS: In seven healthy subjects, the pulmonary hemodynamics
      have been studied by the aid of heart catheterization during a strenuous 30-min
      bicycle IWET where a 4-min work set at the first ventilatory threshold (VT1)
      alternated with a 1-min work set at the second ventilatory threshold (VT2).
      RESULTS: During the IWET, cardiac output increased then remained stable with
      decreasing stroke volume and increasing heart rate, which became near maximal at
      the end of the test. Mean pulmonary arterial pressure increased from rest to the
      fifth minute of exercise and decreased significantly thereafter (P<0.01). An
      identical evolution was observed for mean systemic arterial pressure (SAP).
      CONCLUSION: Pulmonary hemodynamics adapt well in healthy subjects during a
      strenuous IWET despite the performance of exercise bouts of near maximal
      intensity.

PMID- 14600554
TI  - Change in the prevalence of leisure activity with the number of activities
      recalled.
AB  - PURPOSE: The purpose of this study was to examine how the estimated prevalence of
      leisure activity changed when respondents self-reported up to four activities,
      compared with using information only from the respondent's one, two, and three
      most commonly performed leisure activities. METHODS: Information on leisure
      activities, sociodemographics, and body mass index (BMI) categories was collected
      in the year 2000 during a telephone interview of 1813 randomly selected adults
      living in six North Carolina counties. Recommended activity was defined as
      moderate leisure activity > or =5x wk(-1) for > or =30 min per session or
      vigorous leisure activity > or =3x wk(-1) for > or =20 min per session. RESULTS:
      Among respondents, 32.1% reported participation in no leisure activity, 41.7%
      reported one activity, 21.5% reported two activities, 3.8% reported three
      activities, and 0.9% reported four activities during the past month. The largest
      change in prevalence occurred when using two activities compared with one
      activity for recommended activity, overall and by sociodemographic and BMI
      categories. The prevalence of recommended activity determined by using 1, 2, 3,
      or 4 activities was 21.0%, 26.0%, 26.5%, and 26.7%, respectively. CONCLUSION: In
      this study, collecting information on two leisure activities was the most
      efficient balance for population specific accuracy of recommended activity.

PMID- 14600553
TI  - Effects of taper on endurance cycling capacity and single muscle fiber
      properties.
AB  - PURPOSE: It was hypothesized that metabolic adaptations in single muscle cells
      after a taper period are fiber type (I and II) specific and protocol regimen
      dependent. METHODS: After 7-wk intensive endurance training, 22 male cyclists
      (VO2max=4.42 +/- 0.40 L.min(-1)) were randomly assigned to one of three 7-d taper
      groups: the control group (CON, N=7) continued weekly training, the first
      experimental group (INT) maintained training intensity but reduced duration
      (N=7), and the second experimental group (DUR) maintained training duration but
      reduced exercise intensity (N=8). Each cyclist completed a simulated 40-km time
      trial (40TT) before and after tapering on a set of wind-loaded rollers using
      their own bicycle. Muscle biopsies were taken immediately before the 40TT both
      before and after tapering, and analyzed for mATPase, succinate dehydrogenase
      (SDH), cyctochrome oxidase (CYTOX), alpha-glycerolphosphate dehydrogenase (alpha
      GPD), and beta-hydroxyacyl CoA dehydrogenase (beta-HOAD) in Type I and II fibers,
      separately, using quantitative histochemistry. RESULTS: The results showed
      significant (P< or =0.05) increases in SDH (Type I) and mATPase, CYTOX, beta
      HOAD, and SDH (Type II fibers) in the INT group, and significant increases in
      CYTOX (Type I) and beta-HOAD (Type I and II fibers) in the DUR group. Regression
      analysis showed that the change (posttaper minus pretaper) in simulated 40-km
      endurance time was correlated with the change in CYTOX and SDH activity for all
      groups combined (r2=0.62-0.72). CONCLUSION: These results demonstrated that the
      metabolic properties of different fiber types are altered with tapering, that the
      type of taper protocol used influences their physiological adaptation, and that
      improvements in simulated 40-km endurance time were related to changes in
      metabolic properties of the muscle at the single fiber level.

PMID- 14600555
TI  - Amount and bouts of physical activity in a sample of African-American women.
AB  - PURPOSE: To describe physical activity (PA) patterns in a sample of African
      American women in comparison with the national recommendation for moderate PA.
      METHODS: Volunteers (N=55; ages 25-55 yr (mean +/- SD 39.6 +/- 8.7); body mass
      index [BMI] 17.9-56.4 kg.m(-2) (31.3 +/- 7.9 kg.m(-2))) were recruited by word of
      mouth. PA was measured using accelerometers, pedometers, and PA records for two 4
      d periods. RESULTS: Participants accumulated 31.9 +/- 18.0 min.d(-1) in moderate
      to-vigorous PA (MVPA), primarily through short bouts lasting 1-4 (median 11.9
      bouts.d(-1)) and 5-7 min (median 0.6 bouts.d(-1)) but only on 3.1 +/- 2.4 d.wk(
      1). Women with BMI<25.0 kg.m(-2) accumulated more daily PA than those with BMI
      25.0-29.9 kg.m(-2) or > or =30 kg.m(-2) (50.3, 32.0, and 25.3 min.d(-1),
      respectively; P<0.001) and on more days per week (5.8, 3.0, 2.3 d, respectively;
      P<0.001). Of 42 women who completed both PA data collection periods, 17 achieved
      > or =30 min of MVPA on > or =5 of 8 d; however, only two achieved the PA in the
      recommended pattern (one 30-min bout or several 8-10 min bouts). CONCLUSION: The
      current study showed that, although this sample was not sedentary, few
      participants met the activity level recommended for health benefits because
      activity was performed on too few days per week, particularly among overweight
      and obese participants. In addition, the bout pattern for most participants was
      not at the recommended length of at least 8-10 min. This suggests that additional
      emphasis on the recommended days per week and bout length may be necessary when
      counseling individuals about physical activity.

PMID- 14600556
TI  - Physical inactivity: prevalence and associated variables in Brazilian adults.
AB  - PURPOSE: To measure the prevalence of physical inactivity, and variables
      associated with it, in an adult southern Brazilian population. METHODS:
      Population-based cross-sectional study covering a multiple-stage sample of 3182
      subjects aged 20 yr or more. Physical activity was assessed through the short
      version of the International Physical Activity Questionnaire (IPAQ), using home
      interviews with last-week recall. The questionnaire covers leisure, occupation,
      transportation, and housework activities. Physical inactivity was defined as
      fewer than 150 min.wk(-1) spent in moderate or vigorous physical activities. The
      time spent in vigorous activities was multiplied by two. RESULTS: The prevalence
      of physical inactivity was 41.1%. After multivariate analyses, inactivity was
      positively associated with age and socioeconomic status, and inversely associated
      with self-reported health status. Those with white skin color and women who live
      alone rather than with a partner were more likely to have physical inactivity.
      Body mass index showed a significant U-shaped relationship with inactivity among
      men. CONCLUSION: The prevalence of physical inactivity in this Brazilian adult
      population is high, even though lower than reported in studies of leisure-time
      activity alone in other populations. Studies in developing countries may be
      seriously biased if activities during labor, transportation, and housework are
      not assessed.

PMID- 14600557
TI  - RPE during prolonged cycling with and without carbohydrate ingestion in boys and
      men.
AB  - PURPOSE: To examine the effect of prolonged cycling on ratings of perceived
      exertion (RPE) in boys and men and whether carbohydrate (CHO) ingestion would
      lower RPE during exercise. METHODS: Ten boys (9-10 yr) and 10 men (20-25 yr)
      cycled for 60 min at approximately 70% VO2peak on two occasions. In a double
      blind, counterbalanced design, a total volume of 24 mL.kg(-1) body mass of either
      a 6% CHO-electrolyte (CT) or flavored water (WT) beverage was consumed
      intermittently before and during exercise in each trial. Oxygen consumption
      (VO2), ventilation (VE), respiratory rate (RR), RPE (Borg's 6-20 scale), and
      heart rate (HR) were recorded periodically throughout exercise. Plasma glucose
      (GLU) was determined before and after exercise. RESULTS: Postexercise GLU was not
      different between age groups but higher (P<0.001) during CT (5.6 +/- 0.2 mmol.L(
      1)) compared with WT (4.7 +/- 0.1 mmol.L(-1)). CHO ingestion had no effect
      (P>0.05) on VO2, VE, RR, or RPE in either group. RR during exercise was higher
      (P<0.01) in boys (39.0 +/- 2.2 breaths.min(-1)) than in men (30.9 +/- 1.3
      breaths.min(-1)). HR was slightly higher (P=0.047) during CT (160 +/- 3
      beats.min(-1)) compared with WT (156 +/- 4 beats.min(-1)) and increased less over
      time (P<0.01) in boys compared with men. RPE at 5 min of exercise was similar
      (P>0.05) between boys (11.8 +/- 0.7) and men (12.0 +/- 0.7) but increased faster
      (P<0.01) over time in boys. The average exercise RPE was higher (P<0.01) in boys
      (15.8 +/- 0.5) than in men (14.0 +/- 0.4). CONCLUSIONS: The higher and faster
      increase in RPE during exercise in boys, compared with men, may reflect a
      sensitivity to RR that outweighed any effect of CHO ingestion on RPE.

PMID- 14600559
TI  - Tracking of physical activity and aerobic power from childhood through
      adolescence.
AB  - PURPOSE: To evaluate the tracking of physical activity levels (PA) and aerobic
      power (VO2max) in African-American (AA) and Caucasian (CA) youth as they age from
      8 to 16 yr. METHODS: Subjects were 529 girls and 535 boys for whom data were
      obtained at least three times over 7 yr and a subset of 387 girls and 404 boys
      who participated in all years. PA levels were obtained from a survey. VO2max was
      predicted from a cycle ergometer test. RESULTS: Spearman correlation for VO2max
      for years 1-7 for AA boys and girls were similar (rho approximately 0.53). Year 1
      7 correlations for VO2max for the CA boys and girls were similar (rho
      approximately 0.50-0.53). The year 2-7 correlations for PA were similar for the
      AA and CA girls but higher for the AA than the CA boys. The kappa (kappa)
      statistics for VO2max indicated substantial year-to-year agreement on
      categorization (high, moderate, and low), with AA girls having the highest
      agreement and AA boys the lowest. The kappa statistic for high, moderate, and low
      PA groupings in girls of either ethnicity was quite low, whereas the kappa
      statistics for the boys were somewhat better. The general estimating equation
      (GEE) stability coefficients for tracking of VO2max were similar between the
      sexes and ethnicities (P<0.0001). The GEE stability coefficient for PA was better
      for the boys than girls and slightly better for the AA than CA. CONCLUSION:
      Although aerobic power and physical activity levels decline from childhood
      through adolescence, aerobic power tracks better than physical activity levels.
      Because tracking within the cohort is only moderate, change is possible if we
      intervene early in these youth.

PMID- 14600558
TI  - Heart rate versus %VO2max: age, sex, race, initial fitness, and training response
      -HERITAGE.
AB  - PURPOSE: In the HERITAGE Family Study, heart rate (HR) associated with various
      percentages of maximal oxygen intake (VO2max) was used to prescribe exercise
      intensity. When fitness improved, HR at the same power output (PO) decreased, and
      PO was increased to produce the prescribed HR. Although we assumed that subjects
      were again working at the same %VO2max, there were no studies with a large
      heterogeneous population to determine whether this was correct. METHODS:
      Therefore, 653 subjects with complete data were classified by age, sex, race,
      initial VO2max, and VO2max response after 20 wk of training. RESULTS: All groups
      had a significant increase in VO2max and a significant decrease in HR at the same
      absolute PO after training but no difference in HR at the same relative
      intensity. CONCLUSIONS: Training does not affect HR at a given %VO2max in a
      heterogeneous population of men and women, blacks and whites aged 17-65 yr with
      different initial VO2max values and different responses to training.

PMID- 14600560
TI  - Minnesota leisure time activity questionnaire and doubly labeled water in
      adolescents.
AB  - PURPOSES: To validate the energy expenditure estimated from The Minnesota Leisure
      Time Physical Activity Questionnaire (MLTPAQ) with total energy expenditure (TEE)
      measured by doubly labeled water (DLW), and to present and examine the validity
      of an extended version of the MLTPAQ with additional questions about inactivity
      during leisure time (eMLTPAQ), in a sample of Swedish 15-yr-old adolescents.
      METHODS: Thirty-five 15-yr-old adolescents were interviewed using the eMLTPAQ. In
      addition to anthropometry, indirect calorimetry was measured to assess basal
      metabolic rate, and TEE was assessed by the DLW method over a 14-d period.
      RESULTS: Energy expenditure calculated from MLTPAQ correlated well with TEEDLW
      (r=0.49, P<0.01), and the correlation increased when including questions about
      inactivity (r=0.73, P<0.01). However, eMLTPAQ underestimated TEE in 34 of the 35
      students, with a mean difference between the methods of 2.8 MJ.d(-1) (95% limits
      of agreement: -0.1 to 5.6 MJ.d(-1)), which mainly was explained by a relative
      high intensity in the time which remained unreported. CONCLUSION: eMLTPAQ is
      valid in ranking adolescents energy expenditure and in describing patterns of
      leisure time physical activities.

PMID- 14600562
TI  - Training with the International Space Station interim resistive exercise device.
AB  - A unique, interim elastomer-based resistive exercise device (iRED) is being used
      on the International Space Station. PURPOSE: This study characterized iRED
      training responses in a 1-g environment by: 1) determining whether 16 wk of high
      intensity training with iRED produces increases in muscle strength and volume and
      bone mineral density (BMD), 2) comparing training responses with iRED to free
      weights, and 3) comparing iRED training responses at two training volumes.
      METHODS: Twenty-eight untrained men were assigned to four groups of seven
      subjects each: a no exercise control group (CON), an iRED group who trained with
      three sets/exercise (iRED3), a free-weight group (FW) who trained with three
      sets/exercise, and an iRED group who trained with six sets/exercise (iRED6).
      Training exercises included squat (SQ), heel raise (HR), and dead lift (DL)
      exercises, 3 d.wk(-1) for 16 wk. RESULTS: For CON, no changes occurred pre- to
      posttraining. For iRED3, increases (P< or =0.05) in one-repetition maximum (1-RM)
      strength (SQ 21 +/- 4%, HR 17 +/- 4%, DL 29 +/- 5%), leg lean mass (3.1 +/- 0.5%)
      by dual energy x-ray absorptiometry (DXA), and thigh (4.5 +/- 0.9%) and calf (5.9
      +/- 0.7%) muscle volume (by magnetic resonance imaging) occurred after training
      with no changes in BMD (DXA). For FW, increases in 1-RM strength (SQ 22 +/- 5%,
      HR 24 +/- 3%, DL 41 +/- 7%), whole body (3.0 +/- 1.1%) and leg lean mass (5.4 +/-
      1.2%), thigh (9.2 +/- 1.3%) and calf (4.2 +/- 1.0%) muscle volumes, and lumbar
      BMD (4.2 +/- 0.7%) occurred after training. For iRED6, all responses were similar
      to iRED3. CONCLUSION: High-intensity training with the iRED produced muscle
      responses similar to FW but was not effective in stimulating bone. Bed rest and
      spaceflight studies are needed to evaluate the effectiveness of the iRED to
      prevent microgravity deconditioning.

PMID- 14600563
TI  - Effect of creatine and weight training on muscle creatine and performance in
      vegetarians.
AB  - PURPOSE: To compare the change in muscle creatine, fiber morphology, body
      composition, hydration status, and exercise performance between vegetarians and
      nonvegetarians with 8 wk of creatine supplementation and resistance training.
      METHODS: Eighteen VG and 24 NV subjects (19-55 yr) were randomly assigned (double
      blind) to four groups: VG + creatine (VGCr, N=10), VG + placebo (VGPl, N=8), NV +
      creatine (NVCr, N=12), and NV + placebo (NVPl, N=12). Before and at the end of
      the study, muscle biopsies were taken from the vastus lateralis m, body
      composition was assessed by DXA, and strength was assessed using 1-RM bench press
      and leg press. Subjects participated in the same 8-wk resistance-training
      program. Creatine dosage was based on lean tissue mass (0.25 g.kg(-1) LTM.d(-1) x
      7 d; 0.0625 g.kg(-1) LTM.d(-1) x 49 d). RESULTS: Biopsy samples indicated that
      total creatine (TCr=free Cr + PCr) was significantly lower in VG compared with NV
      at baseline (VG=117 mmol.kg(-1); NV=130 mmol.kg(-1); P<0.05). For Cr subjects,
      there was a greater increase in PCr, TCr, bench-press strength, isokinetic work,
      Type II fiber area, and whole-body lean tissue compared with subjects on placebo
      (P<0.05). Vegetarians who took Cr had a greater increase in TCr, PCr, lean
      tissue, and total work performance than nonvegetarians who took Cr (P<0.05). The
      change in muscle TCr was significantly correlated with initial muscle TCr, and
      the change in lean tissue mass and exercise performance. These findings confirm
      an ergogenic effect of Cr during resistance training and suggest that subjects
      with initially low levels of intramuscular Cr (vegetarians) are more responsive
      to supplementation.

PMID- 14600561
TI  - Effect of muscle oxygenation during resistance exercise on anabolic hormone
      response.
AB  - PURPOSE: The mechanisms that underlie the affect of acute program variables on
      muscle growth and strength development for strength/power athletes have been of
      great interest. This investigation examined the affects of two different
      resistance exercise protocols on muscle oxygenation, and the anabolic hormonal
      response to such exercise. METHODS: Eleven experienced resistance-trained male
      athletes performed four sets of the squat exercise using either a low-intensity,
      high-volume (LI; 15 repetitions at 60% one-repetition maximum [1-RM]) or high
      intensity, low-volume (HI; 4 repetitions at 90% 1-RM) load. Venous blood samples
      were obtained before (Pre), immediate (IP), 20- (20P), and 40-min (40P)
      postexercise. Continuous-wave near-infrared spectroscopy was used to measure
      oxygen desaturation during exercise. RESULTS: No differences in muscle
      deoxygenation were seen between LI and HI. However, time-dependent postexercise
      reoxygenation was significantly different between the two exercise sessions (35.3
      +/- 17.4 s vs 24.5 +/- 14.3 s in LI and HI, respectively). Testosterone and
      growth hormone (GH) concentrations were significantly elevated from Pre at IP,
      20P, and 40P in both LI and HI. GH concentrations were higher (P<0.05) for LI
      than at HI at 20P and 40P. CONCLUSION: Muscle oxygen recovery kinetics appeared
      to be influenced by differences in the intensity and volume of exercise, and
      delayed reoxygenation appears to affect the GH response to exercise.

PMID- 14600564
TI  - The effect of smoking on clinical outcome and complication rates following
      Ilizarov reconstruction.
AB  - OBJECTIVE: To determine the effect of smoking on outcome and complication rates
      following Ilizarov reconstruction. DESIGN: We performed a retrospective review of
      84 adult patients (86 limbs) who underwent Ilizarov reconstruction. There were 39
      "limbs" in nonsmokers and 47 "limbs" in active smokers. Complications and an
      outcome score based on ASAMI (Association for the Study and Application of the
      Methods of Ilizarov) criteria were recorded for each patient. DATA ANALYSIS AND
      RESULTS: There were 35 major complications including 15 malunions/nonunions, 7
      refractures, 8 persisting infections, and 5 amputations. Results were measured
      using the ASAMI outcome scale. There were significantly more poor results in the
      smoking group than in the nonsmoking group (18/47, 38% versus 4/39, 10%; P =
      0.003). Seven of eight patients with persisting infection were smokers (P =
      0.049). There was a higher incidence of nonunion in the smoking group (P =
      0.031). All five amputations were in smokers (P = 0.035). CONCLUSION: Smokers had
      a higher percentage of poor results (P = 0.01), due primarily to higher
      complication rates. Smoking is a significant, potentially remediable risk factor
      for failure following Ilizarov reconstruction, and cessation strategies are of
      paramount importance prior to initiating treatment.

PMID- 14600565
TI  - Ilizarov compression over a nail for aseptic femoral nonunions that have failed
      exchange nailing: a report of five cases.
AB  - OBJECTIVE: To evaluate a new operative treatment of femoral nonunion following
      failed exchange nailing. DESIGN: Retrospective review, consecutive series.
      SETTING Office-based orthopaedic practice. PATIENTS: Five consecutive patients
      (ages 31-67 years) were referred in with a femoral nonunion following exchange
      nailing an average of 28 months (range 11-55) after the initial traumatic injury.
      The patients had undergone an average of 5 (range 2-8) previous surgeries on the
      femur. No patient had signs or history of bone infection or segmental bone loss
      at presentation. All patients had diaphyseal or diaphyseal-metaphyseal
      oligotrophic nonunions and had failed an average of 2 (range 1-3) previous
      exchange nailings. INTERVENTION: Slow compression (0.25 to 0.50 mm per day) of
      the nonunion site over a new, smaller diameter nail using an Ilizarov external
      fixator. MAIN OUTCOMES MEASUREMENTS: Clinical and radiographic evidence of bone
      union, ambulation, pain, residual deformity, or shortening. RESULTS: All
      nonunions healed without the need for further nonunion surgery. The external
      fixator was removed at an average of 133 days (range 86-238 days). No deep
      infections occurred in any patient. All patients experienced some degree of pin
      site irritation. At the most recent follow-up (average 45 months; range 12-75
      months), all patients had improved their functional ambulatory status and had
      discontinued or decreased the use of assistive devices to walk. All patients were
      full weight bearing. Average pain, as rated on a 0 to 10 Visual Analogue Scale,
      decreased from 8 of 10 before treatment to 1 of 10 after treatment. No patient
      experienced a clinically significant worsening of leg length discrepancy.
      CONCLUSIONS: Slow compression over an intramedullary nail using external fixation
      successfully promotes the healing of problematic femoral nonunions that have
      failed one or more prior exchange nailings.

PMID- 14600566
TI  - Neurovascular and tendinous damage with placement of anteroposterior distal
      locking bolts in the tibia.
AB  - OBJECTIVE: To determine the proximity of anteroposterior locking bolts inserted
      into the distal metaphyseal tibia to nearby neural, vascular, and tendinous
      structures. DESIGN: A cadaver study. SETTING: University trauma center. METHODS:
      Sixteen legs (8 matched pairs) were nailed in either neutral (Group 1) or 10
      degrees of internal rotation (Group 2) and locked using one anteroposterior bolt.
      The anterior tibial and extensor hallucis longus tendons and neurovascular bundle
      were identified, and their respective locations in relation to the bolt head were
      measured. Average distances were calculated for each structure in each group and
      statistically compared. Damage to any structure was noted at final dissection.
      RESULTS: Average distances from the bolt head to the neurovascular bundle,
      extensor hallucis longus, and anterior tibial tendons were 0.6, 0.5, and 1.6 mm,
      respectively, for Group 1 and 1.0, 1.5, and 1.8 mm, respectively, for Group 2
      legs. Statistical comparison of distances for each anatomic entity for the two
      groups revealed no detectable significant differences (P = 0.7, 0.4, 0.7,
      respectively). For all specimens, the rate of nerve, artery, extensor hallucis
      longus, and anterior tibial tendon injury was 25%, 19%, 0%, and 6%, respectively.
      However, the incidence of at least one structure damage in Group 1 legs was 63%
      versus 12% in Group 2 specimens (P = 0.2). CONCLUSION: Anteroposterior distal
      tibial locking bolts lie in close proximity to the neurovascular bundle. With
      standard percutaneous techniques, these structures can be damaged. Although 10
      degrees of internal rotation does not statistically affect the measured distance
      of the locking bolt to the neurovascular bundle, it appears to decrease the
      incidence of neurovascular injury. This difference may best be explained by the
      necessary path the drill bit must take through the soft tissues to reach the
      underlying bone. Regardless of nail orientation, larger incisions with careful
      dissection and clear visualization of the anatomy are recommended to help prevent
      this complication.

PMID- 14600568
TI  - The effect of age on gene expression in adult and juvenile rats following femoral
      fracture.
AB  - OBJECTIVE: To compare mRNA gene expression during fracture healing in young and
      adult rats. DESIGN: Gene expression was measured at zero, 1, 2, 4, 6, 8 and 10
      weeks after fracture (6 rats/age/time point) in rats at 6 and 26 weeks of age at
      surgery. SETTING: AAALAC-accredited vivarium of an independent academic medical
      center. ANIMALS: Female Sprague-Dawley rats at 6 and 26 weeks of age.
      INTERVENTION: An intramedullary rod was placed retrograde in the left femur, and
      a simple transverse closed middiaphyseal fracture was induced. MAIN OUTCOME
      MEASUREMENTS: mRNA gene expression was measured for 34 genes for extracellular
      matrix, osteoblasts, bone morphogenic protein, inflammation, cytokine, and
      receptor genes. RESULTS: The young rats reached radiographic union by 4 weeks
      after fracture, whereas the adult rats took 8 to 10 weeks to unite. All genes
      studied increased in mRNA expression with a peak at 1 to 2 weeks after fracture.
      All genes in the young rats then subsided to baseline by 4 weeks after fracture.
      However, during the longer period needed for radiographic union in the adult
      rats, only genes related to bone matrix, osteoblastic markers, angiogenesis, and
      the fibroblast growth factors remained significantly up-regulated at 4 and 6
      weeks after fracture. Genes related to cartilage, Indian hedgehog, the bone
      morphogenetic proteins, and transforming growth factor-beta came to undetectable
      baseline values in the adult rats prior to radiographic union. CONCLUSIONS: Most
      stimulators of bone healing are not expressed during the later stages of fracture
      repair in adult rats. Other genes must control bone growth to bridge the fracture
      gap.

PMID- 14600567
TI  - Vacuum-assisted wound closure (VAC therapy) for the management of patients with
      high-energy soft tissue injuries.
AB  - OBJECTIVE: To evaluate the results of a vacuum-assisted closure device in
      patients presenting with open high-energy soft tissue injuries. DESIGN:
      Consecutive nonrandomized clinical study. SETTING/PARTICIPANTS: From August 1999
      through October 2000, 21 patients, with 21 high-energy soft tissue wounds (6
      tibial, 10 ankle, and 5 with wounds of the forearm, elbow, femur, pelvis, and a
      below-knee stump) were treated with a vacuum-assisted closure device at a Level 1
      trauma center. INTERVENTION: A negative atmospheric pressure device used for the
      management of complex open injuries. Infected wounds had dressings changed every
      48 hours, whereas all others had dressings changed every 72 to 96 hours. MAIN
      OUTCOME MEASUREMENTS: The duration of vacuum-assisted closure use, final wound
      closure outcome, costs versus standard dressing changes or free flaps, and a list
      of all complications were recorded. All patients were followed for 6 months
      postcoverage. RESULTS: Patients averaged 4.1 sponge changes, 77% performed at
      bedside, with the device used an average of 19.3 days. Twelve wounds (57%)
      required either no further treatment or a split-thickness skin graft, and 9 (43%)
      required a free tissue transfer. CONCLUSIONS: The vacuum-assisted closure appears
      to be a viable adjunct for the treatment of open high-energy injuries.
      Application can be performed as a bedside procedure but additional soft tissue
      reconstruction may be needed for definitive coverage. This device does not
      replace the need for formal debridement of necrotic tissue, but it may avoid the
      need for a free tissue transfer in some patients with large traumatic wounds.

PMID- 14600569
TI  - Phenotype and functional characteristics of HIV-specific cytotoxic CD8+ T cells
      in chronically infected patients: dual effects of highly active antiretroviral
      therapy.
AB  - BACKGROUND: Cytotoxic CD8+ T cells (CTLs) are critical for the control of viral
      infections. Although these cells can be recognized in most HIV-infected
      individuals, they fail to successfully control HIV replication. Distinct
      functional defects seem to limit their efficacy in HIV infection, although they
      have been not fully elucidated. PATIENTS AND METHODS: Blood lymphocytes collected
      from 61 HLA-A0201+, untreated, chronically HIV-infected individuals were examined
      for the presence of CTLs against epitopes from HIV Gag and Pol proteins, using
      tetrameric complexes. Several functional aspects of these cells were further
      analyzed (immunophenotype; ability to produce interferon-gamma (IFN-gamma) in
      response to the specific peptide; proliferative capacity; and cytolytic
      activity). Lymphoproliferative responses of these cells confronting different
      stimulus were also evaluated. A longitudinal analysis was carried out in a
      subgroup who underwent antiretroviral therapy and were followed for 6 months.
      RESULTS: CD8+ T cells staining with the tetramer complexes (Tet+) were detected
      in 44% of patients, with TetGag+ cells being more frequently detected and at
      higher levels than TetPol+ cells. Most Tet+ cells expressed a memory phenotype,
      showed an impaired ability to produce IFN-gamma when stimulated with the cognate
      peptide, and showed a very low expansion when cultured in the presence of the
      peptide. There was a negative correlation between the proportion of Tet+ cells
      producing IFN-gamma and plasma HIV-RNA. Although Tet+ cells diminished in most
      individuals after beginning antiretroviral therapy, some patients showed de novo
      appearance of Tet+ cells. CONCLUSIONS: Most Tet+ cells in chronic HIV-infected
      individuals express a memory phenotype and show an impaired production of IFN
      gamma and a lower proliferative response to specific HIV antigens. Interestingly,
      some individuals under successful antiretroviral therapy may show de novo
      appearance of specific CTLs. The implications of these findings are relevant for
      a better understanding of virus-host interactions.

PMID- 14600570
TI  - Field evaluation of an improved assay using a heat-dissociated p24 antigen for
      adults mainly infected with HIV-1 CRF02_AG strains in Cote d'Ivoire, West Africa.
AB  - The aim of this study was to evaluate the heat-dissociated p24 antigen (HD p24
      Ag) assay as an alternative low-cost tool for diagnosis of HIV-1 infection and
      quantitation of HIV-1 RNA levels in African adults mainly infected with HIV-1
      CRF02_AG strains. One hundred seventeen plasma specimens were obtained from HIV-1
      seropositive subjects enrolled in the ANRS 1220 PRIMO-CI cohort (Abidjan, Cote
      d'Ivoire, West Africa). Results of the HD p24 Ag assay were comparable with those
      of HIV-1 RNA levels quantified in the same antibody-positive plasma samples by
      the Amplicor HIV-1 Monitor assay (1.5 version; Roche Diagnostics, Indianapolis,
      IN): sensitivity, 95.7% versus 96.6%, respectively; specificity (evaluated with
      samples from 75 seronegative subjects), 94.7% versus 100%, respectively. HD p24
      Ag and HIV-1 RNA assays were weakly correlated (Spearman coefficient correlation,
      r = 0.33; P < 0.001) except for HIV-1 RNA levels of >/=5 log10 copies/mL (r =
      0.62; P < 0.001). Quantitation of HD p24 antigenemia in 76 plasma specimens from
      14 patients treated with highly active antiretroviral therapy demonstrated weaker
      changes during treatment than those observed with the HIV-1 RNA assay. Follow-up
      of infected patients using both markers showed different results. The reliability
      of the HD p24 Ag assay is questionable for clinical and biologic management as a
      surrogate tool for measurement of HIV-1 RNA levels in Africa.

PMID- 14600571
TI  - Low rate of mother-to-child transmission of HIV-1 after nevirapine intervention
      in a pilot public health program in Yaounde, Cameroon.
AB  - OBJECTIVE: To determine the percentage of infected children for whom nevirapine
      (NVP) was used to prevent peripartum mother-to-child transmission (MTCT) of HIV
      in Yaounde, Cameroon. DESIGN: The study was a prospective Public Health Pilot
      Program covering a 3-year period (January 2000-December 2002). METHODS: Counseled
      and consenting HIV-1-positive pregnant women were given a single dose of NVP at
      the onset of labor. Babies were given 2 mg/kg NVP syrup within the first 72 hours
      of life. NVP-treated children were regularly followed up and examined for HIV-1
      infection at 6-8 weeks and 5-6 months through plasma viral load (VL)
      quantification with the bDNA system. RESULTS: One hundred twenty-three children
      were diagnosed with perinatal HIV-1 infection at 6-8 weeks and 5-6 months.
      Thirteen children (10.6% [13/123]; 95% confidence interval, 5.1-16) were infected
      and presented with high VLs, in general >500,000 copies/mL. Two children had
      intermediate VLs (between 50 and 3500 copies/mL) at both time points. One hundred
      seven children (87%) were considered not infected at 6-8 weeks of age.
      CONCLUSIONS: Our results indicate that the HIV-1 MTCT rate 6-8 weeks after NVP
      administration was not >13% (16/123), thus demonstrating the effectiveness of NVP
      for lowering the risk of HIV-1 MTCT in real-life settings.

PMID- 14600572
TI  - Barriers to antiretroviral adherence for patients living with HIV infection and
      AIDS in Botswana.
AB  - BACKGROUND: Botswana has the highest rate of HIV infection in the world,
      estimated at 36% among the population aged 15-49 years. To improve antiretroviral
      (ARV) treatment delivery, we conducted a cross-sectional study of the social,
      cultural, and structural determinants of treatment adherence. METHODS: We used
      both qualitative and quantitative research methodologies, including
      questionnaires and interviews with patients receiving ARV treatment and their
      health care providers to elicit principal barriers to adherence. Patient report
      and provider estimate of adherence (>/=95% doses) were the primary outcomes.
      RESULTS: One hundred nine patients and 60 health care providers were interviewed
      between January and July 2000; 54% of patients were adherent by self-report,
      while 56% were adherent by provider assessment. Observed agreement between
      patients and providers was 68%. Principal barriers to adherence included
      financial constraints (44%), stigma (15%), travel/migration (10%), and side
      effects (9%). On the basis of logistic regression, if cost were removed as a
      barrier, adherence is predicted to increase from 54% to 74%. CONCLUSIONS: ARV
      adherence rates in this study were comparable with those seen in developed
      countries. As elsewhere, health care providers in Botswana were often unable to
      identify which patients adhere to their ARV regimens. The cost of ARV therapy was
      the most significant barrier to adherence.

PMID- 14600573
TI  - Effect of maternal HIV and malaria infection on pregnancy and perinatal outcome
      in Zimbabwe.
AB  - OBJECTIVE: To investigate the effect of isolated or concomitant infection with
      malaria and HIV on pregnancy and neonatal outcome. METHODS: Data were collected
      on pregnant women admitted during the rainy seasons in the obstetric division of
      a district referral hospital in northern Zimbabwe in 2000 and 2001. The effects
      of malaria and HIV infection were determined by multivariate analysis. RESULTS:
      The prevalence of HIV seropositivity and symptomatic malaria in 986 pregnant
      women was 8.3% and 14.7%, respectively. HIV-infected women were more likely to
      develop malaria attacks during pregnancy than seronegative women (odds ratio [OR]
      = 3.96, 95% confidence interval (CI): 2.42-6.46). Malaria and HIV infections were
      associated with increased risk of stillbirth (OR = 4.74, 95% CI: 1.34-16.78) and
      preterm delivery (OR = 4.10, 95% CI: 2.17-7.75), respectively. They were
      independently associated with increased risk of low birth weight (malaria: OR =
      10.09, 95% CI: 6.50-15.65; HIV: OR = 3.16, 95% CI: 1.80-5.54) and very low birth
      weight (malaria: OR = 5.04, 95% CI: 1.00-25.43; HIV: OR = 10.74, 95% CI: 2.12
      54.41), low Apgar score (malaria: OR = 4.45, 95% CI: 1.42-13.94; HIV: OR = 5.94,
      95% CI: 1.66-21.30), and fetal growth restriction (malaria: OR = 3.98, 95% CI:
      2.51-6.30; HIV: OR = 4.07, 95% CI: 2.40-6.92). Dual infection with malaria and
      HIV was associated with increased risk of maternal, perinatal, and early infant
      death. CONCLUSIONS: Women with single HIV or malaria infection have a
      significantly increased risk of adverse outcomes of pregnancy and childbirth.
      Dual infection has additional detrimental effects on maternal and infant survival
      in an area where HIV and malaria coexist.

PMID- 14600574
TI  - MDR1 gene polymorphisms and phase 1 viral decay during HIV-1 infection: an adult
      AIDS Clinical Trials Group study.
AB  - Human CD4+ T cells express P-glycoprotein (P-gp), the ATP binding cassette efflux
      transporter encoded by MDR1. A common MDR1 single-nucleotide polymorphism in exon
      26 (C3435T), which is linked to an exon 21 polymorphism (G2677T/A) and reportedly
      alters expression, has been associated with greater CD4+ T-cell increases during
      antiretroviral therapy. P-gp overexpression prevents apoptosis and inhibits HIV-1
      replication in model systems, suggesting a potential effect on T-cell turnover.
      This study explored relationships between MDR1 polymorphisms and phase 1 viral
      decay among 31 HIV-infected individuals initiating antiretroviral therapy.
      Position 3435 genotypes were CC in 7 (23%), CT in 14 (45%), and TT in 10 (32%).
      Position 2677 genotypes were GG in 8 (26%), GT in 18 (58%), and TT in 5 (16%).
      There was no significant relationship between allelic variants in either exon 26
      or 21 and phase 1 or phase 2 viral decay, changes in lymphocyte subsets over
      time, or plasma trough ritonavir concentrations. It is concluded with 95%
      confidence that phase 1 viral decay differences between exon 26 TT and CC groups
      are unlikely to exceed 18%.

PMID- 14600575
TI  - Increases in CD4+ T lymphocytes occur without increases in thymic size in HIV
      infected subjects receiving interleukin-2 therapy.
AB  - OBJECTIVE: To examine the potential contribution of the thymus to CD4+ T
      lymphocyte increases in HIV-infected patients receiving intermittent interleukin
      2 (IL-2) therapy. DESIGN: Fifteen HIV-infected patients treated with
      antiretroviral regimens who were enrolled in a study of intermittent IL-2 therapy
      and were willing to undergo serial thymic computed tomography (CT) were
      prospectively studied. METHODS: Thymic CT was performed before and approximately
      6 and 12-17 months after intermittent IL-2 therapy was started. Scans were graded
      in a blinded manner. Changes in lymphocyte subpopulations were determined by flow
      cytometry. RESULTS: Statistically significant increases in CD4+ T lymphocytes
      occurred with IL-2 administration, with a preferential increase in naive relative
      to memory CD4+ T cells. Despite this increase in naive CD4+ T cells, overall
      there was a modest decrease in thymic volume observed during the study period. No
      correlation was found between changes in thymic volume indices and total, naive,
      or memory CD4+ T-lymphocyte counts. CONCLUSIONS: These findings demonstrate that
      the profound CD4+ T-lymphocyte increases seen with intermittent IL-2
      administration are not associated with increases in thymic volume and more likely
      are due to peripheral expansion rather than increased thymic output.

PMID- 14600576
TI  - Cardiopulmonary hospitalizations during influenza season in adults and
      adolescents with advanced HIV infection.
AB  - The etiologic role of influenza in hospitalizations and deaths among persons
      infected with HIV since the introduction of highly active antiretroviral therapy
      (HAART) is not known. A retrospective cohort study was performed of all persons
      aged 15 to 50 years with AIDS or advanced HIV infection enrolled in the Tennessee
      Medicaid program from 1995 through 1999, representing 7368 person-years of follow
      up. The influenza season was defined based on local virus surveillance, and
      hospitalizations were measured for acute cardiopulmonary causes and deaths from
      any cause throughout the year. From 1995 through 1999, cardiopulmonary
      hospitalization rates in HIV-infected patients declined by 53% and death rates
      declined by 77%. The influenza-attributable hospitalization rate was 48 (95%
      confidence interval [CI]: 16-91) per 1000 persons in 1995 and 5 (95% CI: -0.5-11)
      per 1000 persons per year during 1996 through 1999, after the introduction of
      HAART. Influenza-associated hospitalizations have declined in patients with HIV
      infection in the post-HAART era. Rates remain comparable to rates in other high
      risk groups for which annual influenza vaccination is recommended, however.

PMID- 14600577
TI  - The interface of perinatal HIV prevention, antiretroviral drug resistance, and
      antiretroviral treatment: what do we really know?

PMID- 14600578
TI  - Zidovudine resistance phenotype and risk of perinatal HIV-1 transmission in
      zidovudine monotherapy-treated mothers with moderately advanced disease.
AB  - The association of phenotypic zidovudine resistance with perinatal transmission
      was evaluated in 74 zidovudine-treated mothers enrolled in the Women and Infants
      Transmission Study through September 1994. Women in the sample had moderately
      advanced disease, with a median CD4+ cell count of 271/microL and a median plasma
      HIV-1 RNA level of 39,811 copies/mL. Factors independently associated with
      zidovudine resistance at delivery (50% inhibitory concentration [IC50], >/=0.1
      microM) in multiple logistic regression included prepregnancy zidovudine use,
      high log plasma HIV-1 RNA level, and low CD4+ cell count. Of 74 mothers, 16 (22%)
      transmitted HIV-1 to their infants. After adjustment for duration of membrane
      rupture and CD8+ cell count, zidovudine resistance (IC50 range, 0.01-2.2 microM)
      was associated with an increased odds of transmission (ORadj, 1.25 per 0.1
      microM; 95% confidence interval, 1.01-1.54), suggesting a decreased effect of
      prenatal zidovudine on preventing transmission in mothers infected with
      zidovudine-resistant virus. However, when the analysis was limited only to those
      mothers infected with virus containing zidovudine resistance mutations, no
      association between phenotypic resistance and transmission remained, indicating
      that phenotype may not provide significant additional information in predicting
      transmission where resistance genotype is known.

PMID- 14600579
TI  - Rates and risk factors for condition-specific hospitalizations in HIV-infected
      and uninfected women.
AB  - BACKGROUND: The rates and risk factors for overall and medical condition-specific
      hospitalizations in HIV-positive women have not been examined in detail or
      compared with rates in risk factor-matched HIV-negative women. OBJECTIVE: To
      determine the rates and risk factors for overall and condition-specific
      hospitalizations. METHODS: Prospective cohort study of 885 HIV-positive women and
      425 HIV-negative women followed for semiannual research visits between 1993 and
      2000 in 4 urban locations in the United States. Outcome measures were
      hospitalization diagnoses with diabetes mellitus, nonacute renal conditions,
      cardiovascular conditions, liver conditions, AIDS defining conditions, and
      overall hospitalizations. Clinical and laboratory risk factors were assessed at
      research visits every 6 months, and effects of risk factors on hospitalization
      rates were calculated using generalized estimating equations and Poisson
      regression. RESULTS: Renal laboratory abnormalities, hypertension, and clinical
      AIDS were each associated with 3 of the 5 condition-specific hospitalization
      rates. Over time, diabetes-, nonacute renal-, and cardiovascular-related rates
      were flat or slightly increased and liver-related rates were significantly
      increased in HIV-positive women. Hospitalization rates with an AIDS-defining
      condition declined sharply in the latter half of the study period. CONCLUSIONS:
      In this population of largely African-American, inner-city, HIV-infected women,
      renal abnormalities, hypertension, and hepatitis C virus infection were common.
      Rate ratios indicated that "non-AIDS" risk factors were important predictors of
      hospitalization. In the highly active antiretroviral therapy era, clinicians must
      pay attention to these risk factors for morbidity and should closely monitor
      renal abnormalities, hypertension, and hepatitis status.

PMID- 14600580
TI  - Gender and hospitalization patterns among HIV-infected drug users before and
      after the availability of highly active antiretroviral therapy.
AB  - We examined highly active antiretroviral therapy (HAART) era and pre-HAART era
      hospitalization rates among 604 HIV-infected drug users in a prospective study in
      Bronx, New York. Medical history and risk behaviors were elicited by semiannual
      interviews. Standardized medical record review abstracted discharge diagnoses for
      all hospitalizations. Hospitalization rates from January 1997 to December 2000
      were compared with rates from January 1992 to December 1996. The rate of
      hospitalizations per 100 patient-years in the HAART era was 49.3 compared with
      44.1 in the pre-HAART era (P = 0.13). Among women, the rate was significantly
      higher in the HAART era than in the pre-HAART era (68.1 vs. 49.4 hospitalizations
      per 100 patient-years, respectively; P = 0.01). In the second era, HAART users
      had lower rates than those who did not use HAART (37.2 vs. 83.4 hospitalizations
      per 100 patient-years, respectively; P < 0.001) for both HIV-associated and non
      HIV-associated illnesses. Multivariate analysis revealed that in the HAART era,
      female gender (relative risk ratio = 1.72, P = 0.03) and not using HAART
      (relative risk ratio = 1.82, P = 0.02) independently predicted increased
      hospitalization risk. In the pre-HAART era, women were at independently higher
      risk of hospitalization (relative risk ratio = 1.36, P = 0.05). Among HIV
      infected drug users, those who use HAART have a decreased risk of
      hospitalization; those who do not use HAART remain at high risk of continuing
      morbidity from both HIV-related and non-HIV-related illness and have high
      hospitalization rates.

PMID- 14600581
TI  - Characteristics of HIV-infected women who do not receive preventive
      antiretroviral therapy in the French Perinatal Cohort.
AB  - OBJECTIVE: To determine the percentage and the profile of women with known HIV-1
      seropositivity who do not receive the prepartum phase of preventive treatment for
      maternofetal transmission. METHODS: An observational study was conducted as part
      of the French Perinatal Cohort, an ongoing nationwide cohort of HIV-infected
      women and their children (followed from birth). This analysis was restricted to
      women who were delivered between 1996 and 1999. RESULTS: Among the 2167 women
      studied, 92 (4.3%) did not receive the prepartum phase of preventive treatment.
      This proportion fell below 10% in 1996 and subsequently stabilized at 3% to 4%.
      The reasons for nontreatment were the woman's refusal (34%), premature delivery
      (8%, before initiation of planned treatment), late diagnosis of maternal HIV
      infection (3%, at the time of delivery), or unmonitored pregnancy (54%). One
      third of the women in this latter category were aware of their seropositivity
      before becoming pregnant. Treated and untreated women did not differ in terms of
      the usual parameters of HIV infection, geographic origin (sub-Saharan Africa vs.
      Europe), or HIV transmission category (sexual vs. intravenous [IV] drug use).
      Untreated women were also less likely than treated women to receive other
      preventive measures such as intrapartum IV zidovudine infusion, treatment of the
      newborn, and formula feeding. Indirect evidence strongly suggested that the
      untreated women were socially marginalized. CONCLUSIONS: The prepartum phase of
      preventive treatment for maternofetal transmission is well accepted by HIV
      seropositive women in France. The proportion of women who do not receive this
      treatment could be further reduced by earlier screening (before or at the
      beginning of pregnancy) and by focusing on a small subgroup of socially
      marginalized women.

PMID- 14600582
TI  - Treating advanced HIV infection.

PMID- 14600583
TI  - AIDS-associated gastrointestinal lymphoma: is there a role for surgery in the
      standard of care?

PMID- 14600584
TI  - CD4 cell count response to nonnucleoside reverse transcriptase inhibitor- or
      protease inhibitor-based highly active antiretroviral therapy in an observational
      cohort study.

PMID- 14600585
TI  - Does prior short-course nevirapine reduce the effectiveness of subsequent
      combination treatment with efavirenz?

PMID- 14600586
TI  - Proceedings from the Association of Bone and Joint Surgeons Symposium on
      Metastatic Bone Disease, November 2002.

PMID- 14600587
TI  - Metastatic disease in long bones: A proposed scoring system for diagnosing
      impending pathologic fractures. 1989.
AB  - A weighted scoring system is proposed to quantify the risk of sustaining a
      pathologic fracture through a metastatic lesion in a long bone. This system
      objectively analyzes and combines four roentgenographic and clinical risk factors
      into a single score. Retrospective analysis of metastatic long bone lesions was
      completed in 78 lesions that had been irradiated without prophylactic surgical
      fixation. Clinical data and roentgenograms were scored prior to irradiation by
      independent observers. The outcome identified 51 lesions that did not fracture
      during the subsequent six months and 27 lesions that fractured within six months.
      A mean score of 7 was found in the nonfracture group, whereas the fracture group
      had a mean score of 10. The percentage risk of a lesion sustaining a pathologic
      fracture could be predicted for any given score. As the score increased above 7,
      so did the percentage risk of fracture. It is suggested that all metastatic
      lesions in long bones be evaluated prior to irradiation. Lesions with scores of 7
      or lower can be safely irradiated without risk of fracture, while lesions with
      scores of 8 or higher require prophylactic internal fixation prior to
      irradiation.

PMID- 14600588
TI  - Advances and challenges in the surgical treatment of metastatic bone disease.
AB  - There are numerous challenges facing the orthopaedic surgeon who treats
      metastatic bone disease in the twenty-first century. The orthopaedic surgeon must
      be familiar with the indications for surgical intervention, the available
      implants for fixation of a given anatomic lesion, the appropriateness of fixation
      versus resection and replacement, and the viability of newer, less invasive
      treatment options for a given lesion. Determination of the best surgical
      candidates still is controversial, especially in the arena of prophylactic
      treatment. Recent advances have made fixation with intramedullary devices and
      standard plates simpler and more rigid. The advent and improvement of
      megaprostheses has made complex joint reconstructions more durable. Advances in
      interventional radiology such as radiofrequency ablation and percutaneous
      vertebroplasty and acetabuloplasty with polymethylmethacrylate (PMMA) continue to
      be promising options for future treatment. Better methods are necessary to
      evaluate the status of the patients preoperatively and postoperatively, to
      classify functional improvement after surgical treatment, and to determine the
      impact of treatment on the quality of life.

PMID- 14600589
TI  - The molecular basis of skeletal metastases.
AB  - Metastasis is the culmination of numerous highly regulated sequences of steps
      that results in the proliferation and migration of cells from the primary site to
      a distant location. The biologic consequence of skeletal metastasis is focal bone
      sclerosis or osteolysis that leads to pain, pathologic fracture, and biochemical
      derangement. The difficulty in determining a point of control for clinical
      application has been because of the numerous systems, substrates, ligands,
      receptors, factors, and pathways that exist. These may be grouped into functional
      mechanisms identifiable by their relevance to the metastatic process. These
      include cell-cell or cell-matrix adhesion, invasion and migration, interactions
      with endothelial cells, growth factor regulation, proteolysis, and stimulation of
      differentiated osteoblast and osteoclast function. The challenge for cancer
      therapy will be to identify means to prevent metastasis or reduce its effect once
      it occurred. This review examines recent advances in the study of molecular
      processes of metastasis, which have identified potential sites and substrates for
      targeting with novel therapies and agents.

PMID- 14600590
TI  - Transforming growth factor-beta in osteolytic breast cancer bone metastases.
AB  - Breast cancers frequently metastasize to the skeleton and cause bone destruction.
      Tumor cells secrete factors that stimulate osteoclasts. The consequent osteolytic
      resorption releases active factors from the bone matrix, in particular
      transforming growth factor-beta (TGF-beta). The released factors then stimulate
      tumor cell signaling, which causes breast cancer cells to make increased amounts
      of osteolytic factors, such as parathyroid hormone-related protein (PTHrP),
      interleukin-11 (IL-11), and vascular endothelial growth factor (VEGF). Therefore,
      tumor cell-bone cell interactions cause a vicious cycle in which tumor cells
      stimulate bone cells to cause bone destruction. As a consequence, the local
      microenvironment is enriched with factors that fuel tumor growth in bone.
      Transforming growth factor-beta is of particular importance because it increases
      breast cancer production of PTHrP. Parathyroid hormone-related protein then
      stimulates osteoblasts to express RANK (receptor activator of nuclear factor
      kappa B) ligand, which in turns enhances osteoclast formation and activity.
      Breast cancer osteolytic metastasis can be interrupted at four points in the
      vicious cycle: by neutralizing PTHrP biologic activity, by blocking the TGF-beta
      signaling pathway in the tumor cells, by inhibiting PTHrP gene transcription, and
      by inhibiting bone resorption.

PMID- 14600591
TI  - Breast cancer metastasis to bone: it is not all about PTHrP.
AB  - Breast cancer shows a predilection for metastasis to bone. Interestingly,
      approximately 80% of patients with breast cancer also have bone metastases
      develop at some point during the course of their disease. Osteolytic breast
      cancer induces bonedestruction via the stimulation of osteoclasts. Breast cancer
      cells produce many known stimulators of bone resorption with significant research
      effort focused on the role of parathyroid hormone-related protein (PTHrP).
      However, a recent prospective clinical trial has questioned the primary role of
      PTHrP in this process. The overexpression of interleukin-8 (IL-8) in metastatic
      breast cancer cells prompted additional investigation of the role of IL-8 in
      osteolysis. Recombinant IL-8 induces the expression of RANKL mRNA and protein in
      osteoblastic cells and stimulates formation of bone resorbing osteoclasts, even
      in the absence of RANKL. The ability of IL-8 to directly stimulate
      osteoclastogenesis via RANKL dependent and independent mechanisms suggests it may
      play an important role in the process of osteoclast formation and function.
      Therefore, we propose that cytokines such as IL-8 are involved in the early
      stages of breast cancer metastasis and initiate the process of osteoclastic bone
      resorption. In this modified model of breast cancer metastasis to bone, PTHrP
      expression is induced later to stimulate the vicious cycle of bone destruction.

PMID- 14600592
TI  - Urokinase plasminogen activator system: a multifunctional role in tumor
      progression and metastasis.
AB  - The urokinase plasminogen activator (uPA) system is central to a spectrum of
      biologic processes including fibrinoloysis, inflammation, atherosclerotic plaque
      formation, matrix remodeling during wound healing, tumor invasion, angiogenesis,
      and metastasis. Binding of uPA with its receptor (uPAR) initiates a proteolytic
      cascade that results in the conversion of plasminogen to plasmin. Plasmin through
      its own proteolytic function degrades a range of extracellular basement membrane
      components and activates others such as the metalloproteinases. Independent of
      catalytic activity, uPAR also is involved in cell signaling, interactions with
      integrins, cell motility, adhesion and invasion, and angiogenesis. Over
      expression of uPA or uPAR is a feature of malignancy and is correlated with tumor
      progression and metastasis. In contrast, inhibition of expression of these
      components leads to a reduction in the invasive and metastatic capacity of many
      tumors. Strategies that target uPA or its receptor with the aim of disrupting the
      interaction between the two or the ligand independent actions of uPAR include
      antisense technology, monoclonal antibodies, cytotoxic antibiotics, and synthetic
      inhibitors of uPA. Targeted therapy is a goal of future cancer treatment and the
      uPA system is a likely candidate for manipulation.

PMID- 14600593
TI  - The mevalonate synthesis pathway as a therapeutic target in cancer.
AB  - Farnesyl transferase inhibitors have emerged as bona fide anticancer agents
      whereas the development of geranylgeranyl transferase inhibitors has been
      mitigated by overt systemic toxicities. Evidence suggests that the therapeutic
      value of farnesyl transferase inhibitors is an indirect result of perturbations
      in the function of geranylgeranylated Rho proteins. To address this question, we
      used inhibitors of the mevalonate synthesis pathway to decrease cellular levels
      of farnesly and geranylgeranly isoprenoids and supplemented our culture systems
      with exogenous isoprenoids accordingly. Using a murine lung alveolar carcinoma
      cell line (Line 1), we report a dose-dependent inhibition of tumor cell
      proliferation, adhesion and invasiveness, in response to alendronate (3-30
      micromol/L) and mevastatin (1-10 micromol/L). Supplementation of cultures with
      geranylgeranyl pyrophosphates (100 micromol/L) was observed to rescue drug
      induced phenotypic changes whereas farnesyl pyrophosphate (100 micromol/L) had a
      minimal effect. Our observations highlight the mevalonate synthesis pathway as a
      target for anticancer therapies and suggest a greater role for geranylgeranylated
      proteins in cellular processes germane to cancer.

PMID- 14600594
TI  - Mechanisms of osteoblastic metastases: role of endothelin-1.
AB  - Certain solid tumors metastasize to bone, causing an osteoblastic response. The
      mechanisms by which tumor cells stimulate this new bone formation are not
      understood completely. We identified three breast cancer lines that cause
      osteoblastic metastases in female nude mice and provide evidence that tumor
      produced endothelin-1 (ET-1) mediates the osteoblastic response. Tumor
      conditioned media and exogenous ET-1 stimulated osteoblast proliferation and new
      bone formation in cultures of calvarias from mice. These effects were blocked by
      endothelin A (ETA) but not by ETB receptor antagonists. Mice inoculated with the
      ZR-75-1 breast cancer line and treated with a selective ETA receptor antagonist
      (ABT-627) had significantly fewer osteoblastic bone metastases and less tumor
      burden compared with untreated mice. In contrast, there was no effect of ABT-627
      on osteolytic bone metastases caused by ET-1-negative breast cancer, MDA-MB-231.
      ABT-627 had no effect on cell growth in vitro or at the orthotopic site (mammary
      fat pad) of ZR-75-1, or MDA-MB-231 cells. Collectively, the data suggest that
      tumor-produced ET-1 mediates osteoblastic bone metastases by stimulating
      osteoblast proliferation and new bone formation. Endothelin A receptor blockade
      may be useful for the prevention and treatment of osteoblastic bone metastases
      attributable to breast or prostate cancer.

PMID- 14600595
TI  - NFkappaB: a pivotal transcription factor in prostate cancer metastasis to bone.
AB  - Prostate cancers frequently metastasize to bone and this accounts for substantial
      morbidity. We investigated the potential role of the transcription factor
      NFkappaB as a central regulator of prostate cancer metastasis using the prostate
      adenocarcinoma cell line, PC-3, in a series of in vitro studies. Wild type PC-3
      cells (PC-3.WT) have high basal levels of NFkappaB signaling, otherwise absent in
      PC-3 cells stably expressing a mutant form of the inhibitory kappa B (IkappaB)
      protein alpha (PC-3.mIkappaB). Although PC-3.WT cells in co-culture with rat bone
      marrow cells enhance bone resorption, no increase was observed in co-cultures
      with PC-3.mIkappaB cells. Similarly, although PC-3.WT cells were invasive in a
      chicken chorioallantoic membrane extravasation model, PC-3.mIkappaB cells lose
      this capacity to invade. NFkappaB reciprocally regulated genes involved in
      cellular invasion, with upregulation of MMP-9 and downregulation of its
      inhibitor, TIMP-1 in PC-3.WT cells, whereas MMP-9 was downregulated and TIMP-1
      was upregulated in PC-3.mIkappaB cells. Finally, high basal gene and protein
      expression of the osteoclast-activating cytokine IL-6, observed in PC-3.WT cells,
      was absent in PC-3.mIkappaB cells. These in vitro experiments suggest NFkappaB as
      an important target to prevent prostate cancer bone metastasis and provide a
      rationale for further study of this transcription factor in metastatic disease.

PMID- 14600597
TI  - Metastatic bone disease: future directions.
AB  - Bone cancer is common and difficult to treat. Current bone-targeted therapies
      include radiation and bisphosphonates. Both treatments can provide pain relief,
      but neither has been shown to prolong survival. Because bisphosphonates are
      osteoclast-targeted therapies, they do not exhibit significant tumor-killing
      properties in humans. Often, patients with asymptomatic skeletal metastases are
      treated with observation. New treatments are needed for patients known to have
      bone metastases and those who are at high risk for having bone metastases
      develop. Enzyme prodrug gene therapy treatment strategies currently are being
      explored for their potential benefit in designing novel therapies for bone
      cancer.

PMID- 14600596
TI  - Renal cell carcinoma bone metastasis: epidermal growth factor receptor targeting.
AB  - Renal cell carcinoma frequently metastasizes to the skeleton in the later stages
      of the disease. Patients with bone metastasis from renal cell carcinoma
      experience severe pain, neurologic compromise, and frequent pathologic fractures.
      These tumors are relatively resistant to chemotherapy and radiation, and the 5
      year survival of patients is less than 10%. The epidermal growth factor receptor
      is overexpressed in human renal cell carcinoma and hypothesized to be a potential
      target in the treatment of bone metastasis. Using in vitro studies, it was shown
      that blockade of the epidermal growth factor receptor was effective in decreasing
      proliferation and receptor autophosphorylation of a human bone-derived renal cell
      carcinoma cell line. In an experimental nude mouse model, treatment with Taxol
      and protein tyrosine kinase inhibitor 166, a small molecule receptor tyrosine
      kinase inhibitor, blocked the growth of renal cell carcinoma in the tibia and
      resulted in decreased bone destruction. The use of protein tyrosine kinase
      inhibitor 166 and Taxol was cytostatic and nontoxic in long-term animal
      experiments. Epidermal growth factor receptor blockade is an exciting potential
      therapy for renal cell carcinoma bone metastasis in humans, but because it is
      cytostatic rather than cytotoxic, its optimal role may be as a supplement to
      cytotoxic chemotherapy. It ultimate role and its relationship to other
      therapeutic interventions remains to be elucidated and validated.

PMID- 14600598
TI  - Molecular mechanisms of bone metastasis and therapeutic implications.

PMID- 14600599
TI  - Evaluation of the patient with carcinoma of unknown origin metastatic to bone.
AB  - Metastatic carcinoma to bone of uncertain primary origin is a common clinical
      diagnostic scenario. I present a simple and effective staging system to identify
      primary malignancies. The role of clinical history, physical examination,
      laboratory studies, and limited radiographic studies are critical to the success
      of this diagnostic strategy. Needle or open biopsy frequently is needed yet
      usually is more effective as a confirmatory study for carcinoma or to rule out
      primary bone sarcomas. Patients who present with a displaced pathologic fracture
      require an urgent diagnostic and treatment plan that does not compromise future
      treatment options and provides durable skeletal reconstruction.

PMID- 14600600
TI  - Validation of cDNA microarray analysis to distinguish tumor type ex vivo.
AB  - Tissue biopsy alone is diagnostic in less than 10% of cases of metastatic bone
      disease with an unknown primary tumor. Accordingly, to delineate the neoplastic
      process in cases of metastatic bone disease, where the primary tumor cannot be
      determined with conventional modalities, new tools are attractive. Complementary
      deoxyribonucleic acid cDNA microarrays may be such a tool. Verification and
      validation of this technology for analysis of specimens ex vivo is mandatory if
      it is to be used to analyze the complexity of heterogenous biologic tissues. To
      convey the issues involved in the clinical application of cDNA microarray
      analysis of tumor specimens ex vivo, a set of experiments analyzing surgically
      resected human specimens is presented. The specific aims of the analysis were to
      assess cDNA microarray reproducibility of serial tissue preparations of tumor
      samples and to confirm that heterogeneity within a given clinical tumor specimen
      does not preclude this technique as a tool to discern tumor types. Complementary
      deoxyribonucleic microarray analysis, as it applies to heterogeneous clinical
      tumor samples in limited numbers, based on preliminary data, seems to be an
      appropriate but still experimental method for distinguishing tumor types.

PMID- 14600601
TI  - Diagnosis of occult bone metastases: positron emission tomography.
AB  - The current standard of practice for the detection of osseous metastatic disease
      is the conventional bone scan of the entire body using technetium-99m methylene
      diphosphonate (Tc-99m MDP). Although Tc-99m MDP scintigraphy is sensitive for the
      detection of advanced skeletal metastatic lesions, early involvement may be
      missed because this technique relies on the identification of the osteoblastic
      reaction of the involved bone rather than the detection the tumor itself.
      Positron emission tomography (PET) has proven to be the gold standard in
      metabolic imaging. Fluorine -18 deoxyglucose (FDG) provides a means of
      quantitating the glucose metabolism, with the amount of tracer accumulation
      reflecting the glucose metabolism: high-grade malignancies tend to have higher
      rates of glycolysis than do low-grade malignancies and benign lesions; therefore,
      high-grade malignancies have greater uptake of FDG than that of low-grade or
      benign lesions. Positron emission tomography has been shown to be superior to
      scintigraphy in the detection of metastases because it detects the presence of
      tumor directly by metabolic activity, rather than indirectly by showing tumor
      involvement due to increased bone mineral turnover. This has allowed the
      detection of metastatic foci earlier with PET than with bone scintigraphy.
      Although the spectrum of PET applications is unknown, it now is approved for the
      diagnosis, staging and restaging of many common malignancies and has shown
      efficacy for the detection of osseous metastasis from several malignancies
      including lung carcinoma, breast carcinoma, and lymphoma.

PMID- 14600602
TI  - Presentation and staging of metastatic bone disease.

PMID- 14600603
TI  - Metastatic breast cancer: overview of treatment.
AB  - Patients with metastatic breast cancer have a median survival of 2 to 3 years.
      Twenty percent of the patients who present with bone-only metastasis will be
      alive at 5 years from diagnosis. Current therapies are aimed at improving the
      quality of life, symptom control, and prolongation of survival. Newer endocrine
      and chemotherapeutic drugs are available to the medical oncologist for care of
      patients with metastatic breast cancer. We will briefly review the new advances
      in the treatment of metastatic breast cancer.

PMID- 14600604
TI  - Biochemical markers and skeletal metastases.
AB  - Bisphosphonate therapy for the treatment of skeletal complications from
      osteolytic metastases has become standard care in patients with cancer who have
      metastatic bone disease. The ability to assess patient response to bisphosphonate
      therapy has been helped by the availability of immunoassays that can measure bone
      collagen breakdown products that are increased in the blood and urine of patients
      with osteolytic metastases. Measurements of the carboxy and amino terminal
      telopeptides in blood and urine particularly have been helpful as adjunct methods
      to facilitate the treatment of patients with skeletal metastases. These
      biochemical bone markers have been shown to correlate with the extent of skeletal
      involvement and seem to provide a means of monitoring the dose and scheduling of
      bisphosphonate therapy of patients with cancer who have bony metastases.

PMID- 14600605
TI  - Prostate cancer and bone metastases: medical treatment.
AB  - Prostate cancer is the most common malignancy in men in the United States. With
      the long natural history of the disease, management of skeletal morbidity related
      to advanced prostate cancer becomes a major public health issue. The standard of
      care in advanced prostate cancer is androgen deprivation therapy. This may
      accelerate the development of osteoporosis and further exacerbate the risks of
      having adverse skeletal-related events develop. Recently, the use of
      bisphosphonates in men who have not responded to androgen deprivation therapy has
      been shown to reduce the incidence of skeletal-related events with time.
      Questions remain as to whether bisphosphonates should be broadly applied to
      earlier stages of the disease or tailored to men at higher risk of having bone
      related morbidity. Work is ongoing to improve other approaches to the medical
      treatment of bone metastases in patients with advanced prostate cancer including
      the use of radiopharmaceuticals and combined chemotherapy.

PMID- 14600606
TI  - General principles of external beam radiation therapy for skeletal metastases.
AB  - Radiation therapy plays a major role in the treatment of patients with bone
      metastases. The primary goals of treatment include pain relief and relief of
      neurologic symptoms, if present. Approximately 70% of patients will achieve pain
      relief with palliative external beam radiotherapy. Improvement in the severity of
      pain may occur within as few as 48 to 72 hours of initiation of therapy, but in
      some patients significant relief of pain may not occur for 4 weeks after
      completion of therapy. Treatment schemes ranging from 800 cGy in a single
      treatment to 3000 cGy in 10 treatments have not been shown to result in major
      differences in outcome. Treatment decisions must be individualized based on
      factors such as the patient's performance status, life expectancy, location of
      the lesion, and size of area to be treated. External beam radiotherapy is
      recommended after surgical treatment of pathologic fractures or impending
      fractures to decrease the need for a second surgical procedure and improve the
      patient's functional outcome. External beam radiotherapy continues to be an
      important component of the palliative treatment of bone metastases. Its
      integration with newer therapeutic modalities such as vertebroplasty and
      radiofrequency ablation currently is being studied.

PMID- 14600607
TI  - Metastatic disease of the spine: evaluation and treatment.
AB  - Treatment of patients with metastatic disease of the spine continues to be a
      challenging problem. Advances in imaging studies and surgical techniques have
      improved patient outcomes with operative intervention. However, the lack of a
      validated set of criteria to determine spinal instability makes patient selection
      for surgical intervention difficult. Multiple classification systems that assist
      surgeons in determining appropriate operative candidates have been proposed. We
      will review current information on the evaluation and treatment of metastatic
      disease of the spine and discuss classification systems that assist in
      determining appropriate operative candidates.

PMID- 14600608
TI  - Vertebroplasty and kyphoplasty for osteolytic vertebral collapse.
AB  - As many as 70% of patients with cancer and multiple myeloma initially present
      with osteolytic involvement of the spine. These vertebral fractures are
      associated with significant morbidity and mortality and represent a tremendous
      personal and societal burden. Traditional medical and surgical options often are
      inadequate or too invasive for this population debilitated by cancer.
      Vertebroplasty involves the injection of polymethylmethaerylate to strengthen a
      vertebra. This minimally invasive method, which has been adopted by practitioners
      during the past decade to treat symptomatic osteoporotic compression fractures is
      reported to provide quick pain relief in 90% of patients, with only infrequent,
      mostly minor, complications. In patients with osteolytic fractures,
      vertebroplasty is associated with an increased rate of cement leak and less
      predictable pain relief. Kyphoplasty is an extension of vertebroplasty that uses
      an inflatable bone tamp to restore the vertebral body toward its original height
      while creating a cavity to be filled with bone cement. Preliminary data indicate
      that kyphoplasty is a safe procedure associated with a lower risk of cement leak,
      restoration of vertebral body height, and sagittal spinal alignment. In patients
      with osteolytic fractures secondary to multiple myeloma, kyphoplasty yields quick
      pain relief, and is associated with a statistically significant improvement in
      generic health outcome measures.

PMID- 14600609
TI  - Acetabular metastases: planning for reconstruction and review of results.
AB  - The treatment of acetabular bone metastases presents numerous clinical challenges
      including the necessity for careful patient selection for surgery, determination
      of the extent of bone destruction, and providing the patient with stable surgical
      reconstruction of the pelvis. There are relatively few patient series reported in
      the literature to inform treatment planning, surgical reconstruction techniques,
      and patient outcomes. We describe a rationale for assessment of patients with
      acetabular metastases and options for reconstruction. The three general
      principles for surgical treatment of metastatic bone disease (tumor removal,
      filling of the resultant bone defect, and bypass of the defect) are defined for
      acetabular metastases. The results of surgical treatment are described with
      reference to recent articles in the literature. The reconstruction of acetabular
      metastatic disease is a major surgical procedure with a significant risk of
      complications. The surgeon must be certain that the patient's longevity and
      potential improvement in quality of life justify the risk of the operation.

PMID- 14600610
TI  - Treatment of axial skeleton bone metastases.

PMID- 14600611
TI  - Critical evaluation of Mirels' rating system for impending pathologic fractures.
AB  - This project examined the hypothesis that Mirels' rating system for impending
      pathologic fractures is reproducible, valid, and applicable across various
      experience levels and training backgrounds. Twelve true clinical histories and
      corresponding radiographs for patients with femoral metastatic lesions were
      reviewed by 53 participants from five experience levels: orthopaedic residents,
      musculoskeletal radiologists, orthopaedic attendings, fellowship-trained
      practicing orthopaedic oncologists, and radiation or medical oncologists. Each
      examiner provided individual and total Mirels' scores and independent
      determination of impending fracture using clinical judgment. A subset of seven
      histories without prophylactic fixation provided a natural history group. There
      was highly significant agreement across experience categories for overall Kappa
      and for the concordance for individual and overall scores. Kappa analysis showed
      good agreement for site, moderate agreement for type, and fair agreement for size
      and pain. There was no significant difference in overall scores across experience
      levels. The pooled odds ratio favored Mirels rating system over clinical judgment
      regardless of experience level. Overall sensitivity was 91% and specificity was
      35%. Mirels' system seems to be reproducible, valid, and more sensitive than
      clinical judgment across experience levels. However, although the system is a
      valuable screening tool, more specific parameters are needed.

PMID- 14600612
TI  - Risk of pathologic fracture: assessment.

PMID- 14600613
TI  - Evaluation and treatment of metastases to the humerus.
AB  - The humerus is the second most common long bone site of metastatic disease, and
      the proximal third and diaphysis are frequent sites. Purely lytic disease and
      cortical bone destruction increase the risk of fracture more than 50%. For most
      patients, external beam irradiation is effective as a means of pain control and
      halting bone destruction. Fractures of the head or surgical neck can be treated
      with standard endoprostheses, whereas extensive proximal bone destruction is
      treated with custom proximal humeral replacements. Impending and complete
      diaphyseal fractures can be treated effectively with either intramedullary nail
      fixation or plate fixation. Rigid fixation, which can be achieved with dual plate
      fixation, is optimal because patients can begin immediate unrestricted activities
      using the upper extremity. Methylmethacrylate is an effective adjuvant for
      filling defects and for augmenting the fixation of intramedullary nails and
      screws. Postoperative external beam irradiation is necessary to prevent
      progressive bone destruction and subsequent loss of fixation.

PMID- 14600614
TI  - Treatment of metastatic disease of the tibia.
AB  - Metastatic lesions to bone outnumber primary bone malignancies. Osseous
      metastases to the tibia tend to be less common than osseous metastases to other
      long bones. This study examined the treatment options for a population of
      patients with metastatic disease to the tibia, with surgical intervention being
      the cornerstone of treatment for the osseous lesion. A multicenter study had 592
      patients with metastatic disease to the bone, with 26 lesions occurring in the
      tibia (4.4%) during a 13-year period. No patient had concurrent metastases distal
      to the elbow. After confirmation of metastatic disease, treatment consisted of
      surgical intervention in all patients, including plate osteosynthesis,
      intramedullary rodding and cementation, endoprosthetic replacement, and in most
      patients, postoperative radiation therapy. In 96% of patients, the reconstruction
      outlasted their life expectancy. All patients were satisfied with their
      reconstruction. Four complications were encountered in the postoperative period,
      all requiring additional surgery. Aggressive treatment of osseous metastasis is
      justified in patients with metastatic disease despite a limited life expectancy.
      Intervention by an orthopaedic oncologist may result in fewer reconstructive
      failures. Surgical intervention contributes to an improved quality of life and
      limb function, ease of nursing care, and may help in maintaining patient
      independence.

PMID- 14600615
TI  - Metastatic disease of the femur: surgical treatment.
AB  - The senior author's 12-year consecutive series of surgery for metastatic disease
      of the femur was reviewed. Treatment of 97 impending pathologic fractures yielded
      better results than treatment of 85 completed pathologic fractures with less
      average blood loss (438 cc versus 636 cc), shorter hospital stay (7 days versus
      11 days), greater likelihood of discharge to home as opposed to an extended care
      facility (79% versus 56%) and greater likelihood of resuming support-free
      ambulation (35% versus 12%). Internal stabilization with a reconstruction-type
      intramedullary nail provided satisfactory pain relief and functional preservation
      for most patients with impending pathologic femur fractures (69 of 97, 71%),
      although alternate forms of internal fixation (21 of 97, 22%) or cemented
      arthroplasty (seven of 97, 7%) were used successfully. Completed pathologic
      fractures were more likely to require some form of arthroplasty (47 of 85, 55%),
      although reconstruction-type nails (20 of 85, 24%), and other internal fixation
      techniques (18 of 85, 21%) also were used. Modular oncology-type arthroplasty
      systems offered a viable salvage option in both groups. In the absence of
      conflicting goals or contraindications, internal stabilization of impending
      pathologic fractures before the completion of the fracture seems to be reasonable
      and appropriate.

PMID- 14600616
TI  - Cardiopulmonary complications of intramedullary fixation of long bone metastases.
AB  - Intramedullary fixation of long bone metastases is an effective method of
      treating or preventing pathologic fractures. An important complication of this
      technique is the development of pulmonary embolism, which may occur at any number
      of steps during bone manipulation. Passage of normal marrow contents or tumor
      into the pulmonary circulation is thought to cause various biochemical,
      hemodynamic, or physical responses that lead to hypotension, arrythmia, and O2
      desaturation. Death is a known risk of this procedure. Numerous surgical and
      anesthetic strategies have been developed to prevent or treat pulmonary embolic
      phenomena; however, the most important prophylaxis may be a heightened awareness
      of this possibility during any procedure that involves intramedullary
      manipulation of tumor containing bone.

PMID- 14600617
TI  - Endoprosthetic reconstructions for bone metastases.
AB  - The purpose of the current study was to help define the role that endoprosthetic
      reconstructions have in the treatment of metastatic bone disease. Of the 522
      endoprostheses implanted at the University of California at Los Angeles (UCLA)
      between December 1980 and January 2002, 37 (6.9%) were used in 37 patients with
      metastatic disease. Upper extremity locations outnumbered lower extremity
      locations 2:1. The 20 males and 17 females ranged in age from 10 to 82 years,
      with a median age of 54 years. Metastatic renal and breast carcinoma predominated
      and accounted for 60% of the lesions. The lesion was a primary metastasis in 27
      patients (73%) and a revision of failed previous surgery in 10 patients (27%).
      Only five patients experienced local complications none of whom required
      reoperation or amputation. Thirty-three of the 37 patients died of disease
      progression at a median of 12 months (range, 4-49 months). Function after
      endoprosthetic reconstruction for metastatic disease is similar to that of
      function for endoprosthetic reconstructions used for primary malignant tumors,
      but clearly is dependent on the patient's general condition. Although
      infrequently used to treat bone metastases, endoprosthetic reconstruction can be
      a useful alternative reconstruction in selected situations.

PMID- 14600618
TI  - PMMA to stabilize bone and deliver antineoplastic and antiresorptive agents.
AB  - Antineoplastic and antiresorptive drugs added to polymethylmethacrylate cement
      may prevent local cancer progression and failure of reconstructive devices used
      to treat patients with pathologic fractures. We tested the mechanical properties
      of cement containing various amounts of the drugs and found that as much as 2 g
      of either doxorubicin or pamidronate can be added to Simplex cement and the
      cement retains 87% of its compressive and tensile strength after 6 months of wet
      storage. Approximately 1 mg pamidronate elutes from experimental pellets. One
      half of the drug elution occurs within the first day in experiments that combined
      doxorubicin and pamidronate, and within 3 days when pamidronate was the only
      additive. Cement containing these drugs seems to be strong enough, but its
      fatigue strength should be tested before using it clinically. Sufficient amounts
      of the tested drugs elute to have potential biologic activity.

PMID- 14600619
TI  - Operative treatment of long bone metastases: focus on the femur.

PMID- 14600620
TI  - Bone cancer pain.
AB  - BACKGROUND: Bone cancer pain is very common, and patients with this type of pain
      may be difficult to treat. Development of an experimental model for studying this
      condition is critical to advancing an understanding of the mechanisms that cause
      pain in patients with malignant disease. METHODS: A murine model of bone cancer
      was studied. Combined analysis of the extent of tumor-induced bone destruction,
      pain, and neurochemical characterization of the peripheral and central nervous
      systems was performed to investigate bone cancer pain. Disease-induced bone
      destruction was assessed by radiographs and histomorphometry. Pain was assessed
      by spontaneous and elicited behaviors, and neurochemical analysis involved
      immunohistochemical detection of hyperalgesic peptides and neurochemical markers.
      RESULTS: Mice with distal femoral sarcomas exhibited behavioral and neurochemical
      measures of pain. The pain condition created by malignant bone disease was
      distinct neurochemically from inflammatory and neuropathic pain states.
      Experimental evidence indicated that both disease-induced osteolysis and tumors
      themselves contributed to the generation of pain and that peripheral and central
      sensitization of the nervous system was present. CONCLUSIONS: Malignant bone
      disease creates a unique pain state that involves sensitization of the nervous
      system. Major contributors to the pain state within the bone tissue are
      osteoclastic bone resorption and the malignant disease itself.

PMID- 14600621
TI  - Prospective quality of life research in bony metastatic disease.
AB  - Metastatic bone disease is a major factor contributing to the deterioration in
      quality of life in patients with cancer. The decision to surgically stabilize an
      impending or existing pathologic fracture, or to excise a metastatic deposit is
      difficult because of the paucity of conclusive data regarding the efficacy of
      surgery in achieving pain relief, improved function, and quality of life. The
      psychometric properties of quality of life outcomes instruments and the
      differences between pain, function, and quality of life are explored in an
      attempt to define surgical goals. The results of different quality of life
      instruments in existing studies of internal fixation, chemotherapy, radiation
      therapy, and bisphophonate treatment suggest that although the majority of
      patients derive benefit from their treatment, the success of such treatment is
      heavily dependent the quality of life instrument. Existing instruments are
      deficient and obstacles to the design and implementation of quality of life
      assessment in patients with skeletal metastasis are reviewed. Recommendations for
      improving our ability to assess the risk to benefit ratio of surgery include
      moving away from physician reported results, devising more appropriate quality of
      life measurement techniques, analyzing the relationship between pain relief,
      physical function and quality of life, and focusing attention on prospectively
      evaluating optimal treatments for patients as they near the end of life.

PMID- 14600622
TI  - Changing failure into glory, times to remember, no regrets.

PMID- 14600623
TI  - Computer aided design of large-format prefabricated cranial plates.
AB  - The authors' objective in this project was to replace current state-of-the-art
      manual methods for preoperative production (i.e., prefabrication) of large-format
      (>100 cm2) cranioplasties with a system for computer-aided design and direct
      computer-aided manufacture of the implant's shape. This system uses standard 3D
      CT data, requires no specialized training, and produces an accurately fitting
      cranioplasty that can be recast in the physician's material of choice (e.g.,
      polymethylmethacrylate [PMMA] or pre-bent titanium plating). The authors begin by
      locating the cranial defect margin on a skull surface image generated from a 3D
      head CT-scan. A right-to-left mirrored or average 3D skull surface template image
      is then fit to the patient's skull surface image. The area around the defect is
      cut out and stitched to the previously isolated defect margin. This defect
      filling surface is then tapered and 3D printed. The 3D printed implant model is
      then recast in a biocompatible material. Manually generated cranial implants
      produced for five patients were compared with implants resulting from this new
      computer-based method. All five computer-generated implants were better fitting
      and more cosmetically suitable than the manually generated skull plates received
      by these patients. These well-fitting implants are more likely to protect the
      brain from trauma and infection. Therefore, the authors conclude that their new
      production method provides a better result with less expense than current methods
      for preoperative or intraoperative fabrication of large-format cranioplasties.

PMID- 14600624
TI  - Three-dimensional surgical planning for maxillary and midface distraction
      osteogenesis.
AB  - Computerized surgical planning protocols for distraction osteogenesis are still
      in their rudimentary phase. The authors have developed a system to plan
      distraction osteogenesis in craniofacial and maxillofacial surgery that uses
      three-dimensional computed tomography scans and computer simulation in a virtual
      reality environment. This involves the creation of a three-dimensional bone model
      of the craniofacial skeleton, which incorporates virtual globes. Virtual
      osteotomies are performed on the bone model and the movements of the bone
      segments are simulated. The program generates a recipe for the linear and the
      angular changes necessary to achieve the desired outcome. The purpose of this
      article is to present this surgical planning process and discuss its use in
      maxillary and midface distraction.

PMID- 14600625
TI  - Management of alveolar clefts.
AB  - The management of alveolar clefts has changed through the years as medical
      knowledge has improved. An alveolar cleft is the result of abnormal primary
      palate formation during weeks 4 to 12 of gestation. The rationale for its closure
      includes 1) stabilizing the maxillary arch, 2) permitting support for tooth
      eruption, 3) eliminating oronasal fistulae, and 4) providing improved esthetic
      results. Methods for closure of the alveolar cleft have been solidified during
      the last century with the use of bone grafting. Secondary bone grafting is now
      the preferred method of treatment, because early grafting has proven detrimental
      to midfacial growth. Various materials for bone grafting have been proposed,
      including iliac crest, cranium, tibia, rib, and mandibular symphysis. Regardless
      of the timing and materials used, the main principles in approaching alveolar
      clefts have been well described. They include 1) appropriate flap design, 2) wide
      exposure, 3) nasal floor reconstruction, 4) closure of oronasal fistula, 5)
      packing bony defect with cancellous bone, and 6) coverage of bone graft with
      gingival mucoperiosteal flaps. Certain alveolar clefts are difficult to manage by
      grafting alone, and orthodontic preparation may be required. Complications of
      alveolar bone grafts include donor site morbidity as well as graft exposure and
      loss.

PMID- 14600626
TI  - Frontoethmoidal encephalomeningocele: new morphological findings and a new
      classification.
AB  - Given a lack of a comprehensive classification for the frontoethmoidal
      encephalomeningocele (FEEM), clinical, photographic, and computed tomography (CT)
      data of 23 nonoperated patients were reviewed. Extracranial pathological findings
      of interest included herniation masses, facial deformities, and frontonasal bone
      morphology. Intracranial pathological findings of interest included morphology of
      the anterior cranial floor and brain malformations. Stereographic software
      processed data from a new-generation CT scanner into three-dimensional pictures
      that revealed some interesting morphological findings not often appreciated (eg,
      herniation mass without underlying external bone defect; mass at location far
      from external bone defect ["sequestrated cephalocele"]; new type of external bone
      defect characterized by a combination of nasoethmoidal and naso-orbital defects;
      correlation between mass, external bone defect, and exit pathway of herniation).
      Given these observations plus current knowledge available in the medical
      literature, a new classification system was developed that covers phenotypes and
      severity of the disease. The "FEEM classification" is an alphanumeric system
      based on facial deformities, external bone defect, exit pathway of herniation,
      and malformation of brain. It was tested in 42 patients for usability and
      validity. When combined with a newly designed "FEEM diagram," relevant
      pathological findings can be recorded in an objective manner so that diagnosis
      becomes more precise and uniform and comparison of outcome is possible. It also
      emphasizes the fact that FEEM has a range of manifestations governed by dynamic
      interaction between structural defects and herniation. Each clinical entity is a
      final result of its own disease course (stable, progressive, or regressive FEEM),
      with a varying degree of communication between the external mass and the central
      nervous system.

PMID- 14600627
TI  - The role of nerve growth factor and brain-derived neurotrophic factor in inferior
      alveolar nerve regeneration in distraction osteogenesis.
AB  - Distraction osteogenesis (DO) has become the mainstay of treatment of mandibular
      hypoplasias. Despite the clinical acceptance of the technique in the last decade,
      little is known of the biological mechanism of bone and soft tissue regeneration.
      The biological response of peripheral nerves to distraction has not been well
      documented. This study examined the role of two neurotrophic molecules, nerve
      growth factor (NGF) and brain-derived neurotrophic factor (BDNF), in DO on nerve
      regeneration of the inferior alveolar nerve (IAN) in an ovine mandible model.
      Twelve animals were randomly divided into three groups and distracted at 5, 10,
      and 15 days using a mandibular osteotomy and uniaxial external distractor. The
      mental nerves and the IAN from the distracted site were harvested at the end of
      the distraction period and examined for the presence of NGF and BDNF using
      immunohistochemistry. Nerve growth factor expression was increased at both sites,
      whereas BDNF was only expressed at the mental nerve on the distracted side. Nerve
      growth factor and BDNF are involved in the response of the peripheral nerves to
      injury. Mechanical force applied to the IAN by distraction may lead to detachment
      of Schwann cells from their axons, leading to segmental degeneration. The
      resulting myelin sheath debris may serve as a trigger for higher expression of
      NGF and BDNF, facilitating Schwann cell proliferation and remyelination of the
      affected segment. Distraction of the mandible may serve as a source of subacute
      injury to the IAN and influence NGF and BDNF.

PMID- 14600628
TI  - Pediatric tissue expansion: indications and complications.
AB  - Tissue expansion has become a major reconstructive modality in the past 30 years.
      Its application in the pediatric population has allowed the plastic surgeon to
      achieve functional and esthetic goals that were previously unobtainable. Tissue
      expansion is a major treatment modality in the management of giant congenital
      nevi and secondary reconstruction of extensive burn scars, allowing sensate
      tissue of similar color, texture, and thickness to be used to resurface the
      affected areas. One must be prepared for complications when using tissue
      expanders, however, because complications are inherent in the process of
      expanding skin utilizing repeated filling of implanted foreign bodies.
      Complication rates increase when serial expansion of the same tissues is
      performed repeatedly or if expanders are placed in the lower extremities.
      Outcomes are dependent on thorough planning, meticulous technique, close follow
      up, and patient compliance. Tissue expansion has revolutionized plastic surgery
      in the last 30 years. This technique can be applied to a considerable breadth of
      reconstructive problems in the pediatric population. Tissue expansion has
      permitted the plastic surgeon to achieve the goals of reconstruction with tissue
      of similar color, texture, and thickness, with minimal donor site morbidity.
      Preservation of sensation in a durable flap has allowed the surgeon to achieve
      acceptable functional as well as esthetic goals simultaneously.

PMID- 14600629
TI  - Desmoplastic ameloblastoma in the mandible.
AB  - The desmoplastic variant of ameloblastoma (DA) is characterized by unique
      histological and radiographic features. It is histologically characterized by an
      abundance of densely collagenous stroma with small nests and strands of likely
      compressed odontogenic epithelium. Although radiographic examination of
      ameloblastomas usually reveals unilocular or multilocular radiolucency, DA may
      appear as a mixed radiopaque-radiolucent lesion. In this case report, a 68-year
      old man who had a complaint of a mass in his right mental region is presented.
      The patient was unable to wear his prosthesis because of an underlying swelling.
      An incisional biopsy was performed. Microscopic examination of the surgical
      specimen revealed large epithelial islands of ameloblast-like cells within
      increased, dense, collagenous desmoplastic stroma. Histopathologically, it was
      diagnosed as DA. Under local anesthesia, the lesion was enucleated. There was no
      recurrence after 32 months of follow-up.

PMID- 14600630
TI  - Congenital melanocytic nevi.
AB  - Congenital nevi are characterized by the appearance of pigmented areas that range
      in size, shape, surface texture, and hairiness. In most cases, the nevus remains
      stable and benign, but because of possible malignant transformation, nevi are
      often excised. In this case, a young boy was born with a hairy nevus below his
      lip extending inferiorly down the left side of his chin and upper neck. After two
      surgical excisions, the wound healing process was interrupted when his incision
      wound was split while jumping on his bed. With the professional assistance of
      occupational therapists, the scar should heal in an esthetically pleasing manner.

PMID- 14600631
TI  - Severe subcutaneous emphysema and pneumomediastinum associated with minor
      maxillofacial trauma.
AB  - In the maxillofacial region, subcutaneous emphysema, which occurs after fractures
      of the pneumatic paranasal sinuses, is a common finding in a maxillofacial
      surgeon's daily practice. Pneumomediastinum secondary to these fractures is a
      less frequent event, however, without thoracic or abdominal injuries. The authors
      report a case of severe subcutaneous emphysema and pneumomediastinum that
      occurred after fractures of the nasal bones and medial orbital wall. The
      etiology, diagnosis, and treatment modalities of mediastinal emphysema are
      discussed.

PMID- 14600632
TI  - Augmentation mentoplasty using a custom-design wire cage.
AB  - Mentoplasty is often a complimentary procedure to rhinoplasty. At least 25% of
      all rhinoplasty patients may need a chin implant to balance facial features
      better. Augmentation mentoplasty using alloplastic implants such as silicone,
      rubber, or other materials provides a simple approach to the treatment of the
      hypoplastic chin. Although these types of implants are readily available in
      developed countries, there are parts of the world where they are unavailable or
      quite expensive. The authors have developed a chin implant made of wire that is
      available throughout the world and is custom designed to the mentum of the
      patient after a cephalometric evaluation. This technique has been used in 125
      patients along with rhinoplasty over the last 20 years at our institution. In an
      initial series of 8 patients, the prosthesis became displaced and was removed in
      2 patients. Since then, a new radiographic technique has been developed to
      demonstrate the shape of the mentum before surgery and new bone formation after
      surgery. By using this special radiographic technique, it was possible to detect
      four types of mentum before surgery and to construct a custom-design wire cage
      according to this shape. The prosthesis is constructed by an orthodontist
      according to the cephalometric measurements and shape of the mentum. By using the
      buccal approach, a pocket is prepared subperiosteally and a wire cage is
      inserted. In the last 20 cases, the wire cage was filled with diced cartilage
      wrapped with Surgicel. The results were esthetically satisfactory in most
      patients. After the shape of the wire prosthesis was modified to conform to the
      shape of the underlying bone better, no displacement of the prosthesis has been
      experienced. In 3 patients, it was necessary to remove the prosthesis when new
      tissue formation began to fill the prosthesis. These specimens were examined
      histologically, and the regenerating tissue was found to be connective tissue
      with a thin layer of bone formation. Most patients could be followed up for only
      3 to 12 years. In all patients, the results have been consistent and the
      procedure has been safe.

PMID- 14600633
TI  - Severe panfacial fracture with facial explosion: integrated and multistaged
      reconstructive procedures.
AB  - Midface fractures, especially if related to traffic accidents, represent a
      remarkable problem from a surgical, psychological, and social standpoint. In
      trauma dynamics, the pattern of the fractures can extend to all bony fragments
      and is often associated with soft tissue injuries and loss of bony structures.
      This can lead to posttraumatic deformities that greatly influence the patient
      psychologically and limit his social rehabilitation, sometimes permanently.
      Panfacial trauma includes midface fractures associated with fractures of other
      areas (i.e., mandible, frontal bone). Orbits and the nasoethmoidal area are often
      involved with loss of soft tissue and, in severe cases, loss of orbital contents.
      We report an unusual complex clinical case representative of this kind of
      pathological profile in which the guidelines described in the literature were
      followed in the reconstructive procedure.

PMID- 14600634
TI  - The application of rapid prototyping techniques in cranial reconstruction and
      preoperative planning in neurosurgery.
AB  - The value of rapid prototype models of the skull in our craniofacial and
      neurosurgical practice was analyzed. Individual skull models of 52 patients were
      produced by means of rapid prototyping techniques and used in various procedures.
      Patients were divided into three groups as follows: group I (26 patients)
      requiring corrective cranioplasty 1) after resection of osseous tumors (15
      patients) and 2) with congenital and posttraumatic craniofacial deformities (11
      patients), group II (10 patients) requiring reconstructive cranioplasty, and
      group III (16 patients) requiring planning of difficult skull base approaches.
      The utility of the stereolithographic models was assessed using the Gillespie
      scoring system. The esthetic and clinical outcomes were assessed by means of the
      esthetic outcome score and the Glasgow Outcome Score, respectively. Simulation of
      osteotomies for advancement plasty and craniofacial reassembly in the model
      before surgery in group I reduced operating time and intraoperative errors. In
      group II, the usefulness of the models depended directly on the size and
      configuration of the cranial defect. The planning of approaches to uncommon and
      complex skull base tumors (group III) was significantly influenced by the
      stereolithographic models. The esthetic outcome was pleasing. The indications for
      the manufacture of individual three-dimensional models could be cases of
      craniofacial dysmorphism that require meticulous preoperative planning and skull
      base surgery with difficult anatomical and reconstructive problems. The
      stereolithographic models provide 1) better understanding of the anatomy, 2)
      presurgical simulation, 3) intraoperative accuracy in localization of lesions, 4)
      accurate fabrication of implants, and 5) improved education of trainees.

PMID- 14600635
TI  - Actinomycosis of the masseter muscle: report of a case and review of the
      literature.
AB  - A rare case of cervicofacial actinomycosis arising primarily in the masseter
      muscle is described. The patient was a healthy 74-year-old woman who was not
      immunocompromised and had no other primary pathological finding in the oral
      cavity. The importance of the differential diagnosis for this unusual infection
      is demonstrated with tumoral pathological findings. Possible predisposing factors
      as well as diagnostic and therapeutic methods are discussed.

PMID- 14600636
TI  - Hard tissue augmentation of the mandibular region with hydroxyapatite granules.
AB  - Interventions in the maxillofacial region for either reconstructive or esthetic
      reasons may sometimes necessitate the augmentation of hard tissues. Although
      autogenous bone grafts are the first choice, donor site morbidity and
      difficulties in shaping make alloplastic implants another reliable alternative.
      Among the alloplastic implants, hydroxyapatite granules, with their high
      biocompatibility, are a good choice. In a total of 11 patients presenting with
      mandibular deformities between 1998 and 2002, contour enhancement was performed
      with the use of hydroxyapatite granules, with a porous structure of 200 microm
      obtained in prefabricated syringes of 0.8 ml. Follow-up ranging from 3 to 46
      months has revealed that the desired contours were established without any
      significant volume loss. No complications regarding the use of hydroxyapatite
      granules were encountered. Hydroxyapatite granules heal by allowing fibrovascular
      tissue ingrowth, do not cause foreign body reactions, and offer ease in use and
      shaping. These advantages make them a comfortable and reliable choice in
      maxillofacial hard tissue augmentation procedures in general and in mandibular
      deformity corrections in particular.

PMID- 14600637
TI  - Longitudinal results of mandibular distraction osteogenesis in hemifacial
      microsomia.
AB  - The aim of this study was to evaluate mandibular distraction therapy by three
      dimensional (3-D) computed tomography (CT) imaging so as to be able to improve
      the treatment results. The study group consisted of eight children (3 male and 5
      female) with hemifacial microsomia. For each child, CT scans of the head were
      available (Pro Speed S Fast Spiral scanner; General Electric). Longitudinal
      measurements of the mandible, bony and soft tissue 3-D reconstructions, and
      masticatory muscles were demonstrated. Three-dimensional CT scans provide
      important data concerning the results of mandibular distraction therapy and
      should be used in treatment evaluation. In some patients and for some muscles
      only, a small increase in the volume of the affected side of the masticatory
      muscles in comparison to the normal side was found 3 years after mandibular
      distraction. In around 50% of the cases, there seems to be a relapse occurring 1
      year after distraction osteogenesis, and this relapse has a progressive character
      when seen 3 years after distraction osteogenesis in comparison to 15 weeks after
      distraction osteogenesis.

PMID- 14600638
TI  - Generalized symptoms in adult women with acute uncomplicated lower urinary tract
      infection: an observational study.
AB  - Several generalized symptoms in acute lower urinary tract infection (UTI) have
      previously been identified in a qualitative study. The aim of the present study
      was to explore the frequency and distribution of generalized symptoms in adult
      women with acute uncomplicated lower UTI in general practice. A total of 398
      women aged 18-87 years consulting for acute dysuria and/or urinary frequency were
      enrolled in an observational study and filled in a structured symptom
      questionnaire. A total of 252 of these had bacteriuria (>or= 10(5)
      uropathogens/mL). Generalized symptoms occurred frequently: feeling unwell 68%,
      week and tired 67%, irritable and restless 53%, and hot 52%. Other symptoms were
      voiding-related symptoms (dysuria 90%, urinary frequency 93%, urge 80%) and
      local, constant symptoms (pressure in the genital area 73%, suprapubic discomfort
      68%). Factor analysis revealed 2 main components of cystitic symptoms: "feeling
      out of sorts" (generalized symptoms) predominantly found among women aged 50-65
      years, and the "distressed bladder" (voiding-related and local, constant
      symptoms) most often in the group aged 18-35 years. No differences in frequency
      or degree of symptoms were related to the presence of bacteriuria. In conclusion,
      generalized symptoms of feeling out of sorts are frequent in adult women with
      acute uncomplicated lower UTI, and equally frequent in all ages whether the
      patient shows bacteriuria or not.

PMID- 14600639
TI  - Insufficient evidence supporting low-intensity warfarin for venous
      thromboembolism (VTE) prophylaxis.

PMID- 14600640
TI  - Hardware update.

PMID- 14600641
TI  - Gastric asthma: a clinical update for the general practitioner.
AB  - Asthma is an inflammatory disease of the airways characterized by increased
      airway reactivity with airflow obstruction. It is exacerbated by multiple
      triggers, and one common, often overlooked trigger is gastroesophageal reflux
      (GER). The prevalence of GER in asthmatics is estimated at between 34% and 80%.
      Up to 24% of asthmatics may have silent GER without the classic reflux symptoms
      (heartburn, acid regurgitation, and dysphagia). Since most patients are initially
      seen at the primary care level, it is essential for the primary physicians to
      recognize the underlying cause of the disease. This review briefly discusses the
      pathogenesis and clinical features of gastric (reflux-triggered) asthma and
      provides clues for its diagnosis in primary care practice. The current diagnostic
      approach to such patients and its management relevant to general practitioners is
      also discussed.

PMID- 14600642
TI  - Incidental finding of a small pancreatic mass in an otherwise healthy patient.

PMID- 14600643
TI  - A conversation with a colleague.

PMID- 14600644
TI  - Tissue regeneration and organ repair: science or science fiction?

PMID- 14600645
TI  - Cancer and the immune response: improving the odds.

PMID- 14600646
TI  - Antileukemic activity of natural killer cells in allogeneic BMT.

PMID- 14600647
TI  - Dissecting oncogenes and tyrosine kinases in AML cells.

PMID- 14600649
TI  - Gene profiling of lymphoma, myeloma, and AML.

PMID- 14600648
TI  - Hepatocellular carcinoma: a clinical update.

PMID- 14600650
TI  - A 38-year-old woman with complicated and steroid-dependent Crohn's disease.

PMID- 14600651
TI  - Unusual finding in a patient with pancreas divisum and abdominal pain.

PMID- 14600652
TI  - Use of prostacyclin in the treatment of sepsis-induced organ failure.

PMID- 14600653
TI  - Outpatient use of major antipsychotic drugs in ambulatory care settings in the
      United States, 1997-2000.
AB  - OBJECTIVE: To describe the prescription of antipsychotic agents in the United
      States and to investigate the association between demographic characteristics,
      clinical diagnosis, and antipsychotic prescribed. METHODS: Four years (1997-2000)
      of data from the National Ambulatory Medical Care Survey (NAMCS) and National
      Hospital Ambulatory Care Survey (NHAMCS) were combined for analysis.
      Distributions for patient age, race, gender, primary diagnosis, and provider's
      medical specialty were assessed. Logistic regression models were developed to
      estimate the probability of receiving either (1) a second-generation vs a first
      generation antipsychotic, or (2) olanzapine vs risperidone, given differences in
      gender, race, age, and primary diagnosis. RESULTS: Nearly 35.9 million ambulatory
      healthcare visits resulted in antipsychotic prescription during 1997-2000, or
      nearly 1% of all healthcare visits for the period. Nearly 30% of these visits
      were to nonpsychiatric physicians. The use of first-generation antipsychotics
      declined during this period, while the use of second-generation antipsychotics
      increased. Risperidone and olanzapine accounted for the majority of second
      generation antipsychotic use. While the mean ages of patients using risperidone
      and olanzapine were similar, the age distributions differed, with risperidone
      showing more frequent use among the young (< 18 years) and the old (> 65 years).
      Patients of nonwhite race were more likely to receive olanzapine than
      risperidone. CONCLUSION: Results from this national survey indicate that second
      generation antipsychotics are being used with increasing frequency and are widely
      used outside of the psychiatric specialty. Differences in age distribution,
      racial representation, and diagnostic representation are associated with drug
      selection, reinforcing the importance of accounting for case-mix factors when
      researching these antipsychotics in observational studies.

PMID- 14600654
TI  - Anti-Yo antibody-mediated paraneoplastic cerebellar degeneration in a man with
      esophageal adenocarcinoma.
AB  - We report a case of paraneoplastic cerebellar degeneration (PCD) associated with
      adenocarcinoma of the esophagus and anti-Yo antibodies in a male patient. The
      patient presented with progressive ataxia, dysarthria, and significant weight
      loss. Extensive work-up suggested paraneoplastic neurologic syndrome. A wide
      search for a cancer was undertaken and a small mass was identified in the distal
      esophagus on upper endoscopy. Biopsies of this lesion revealed well
      differentiated invasive adenocarcinoma of the esophagus. The endoscopic
      ultrasound staged the tumor as T3N1M0. Despite trials of multiple therapeutic
      modalities, the patient's cerebellar dysfunction progressed. This is only the
      second report of PCD caused by esophageal adenocarcinoma and the fourth report of
      anti-Yo antibodies occurring in a male patient.

PMID- 14600655
TI  - Choosing which drug to prescribe.

PMID- 14600656
TI  - Low fasting serum triglyceride level as a precocious marker of autoimmune
      disorders.
AB  - The authors recently reported the occurrence of low fasting serum triglyceride
      (TG) and high free fatty acid (FFA) levels in idiopathic pulmonary fibrosis. TG
      estimation in diverse groups of patients with autoimmune disease or hyperactive
      immune response confirmed the occurrence of a similar decrease of TG. In some
      patients, serum FFA level was also evaluated. TG value in lean and obese patients
      was compared with that in lean (n = 108) and obese (n = 208) control subjects
      without autoimmune disease. In patients affected by autoimmune chronic
      thyroiditis with enhanced concentration of antithyroglobulin antibodies and
      without thyroidal failure (n = 24), lean and obese patients had reduced TG (
      69/%, P < .01 and -52%, P < .0001, respectively). Both lean and obese patients
      affected by chronic active B or C hepatitis (n = 26), with autoantibodies and
      without signs of hepatic insufficiency or cirrhosis, presented reduced TG (-57%,
      P < .01 and -61%, P < .001, respectively). A marked TG decrease (-73%, P < .001)
      was observed in the lean patients affected by lupus-like syndrome (n = 7). The
      lean and obese patients with systemic lupus erythematosus or rheumatoid arthritis
      (n = 11) showed TG decrease (-66%, P < .01 and -55%, P < .05, respectively). In
      patients affected by anamnestic allergy or atopic dermatitis/asthma (n = 66),
      both lean and obese, TGs were reduced (-67%, P < .0001 and -62%, P < .001,
      respectively). In isolated cases of diverse autoimmune diseases (scleroderma,
      APECED [autoimmune polyendocrinopathy, candidiasis, and ectodermal dystrophy],
      urticaria or urticarial vasculitis, Reiter or Sjogren syndromes, ulcerative
      colitis or Crohn's disease, multiple sclerosis or Guillain-Barre syndrome) (n =
      14), decreased TG was also observed both in the lean and obese subjects (-59%, P
      < .01 and -57%, P < .01, respectively). Concerning FFA (n = 69), value in lean
      patients (n = 22) vs that in lean controls (n = 18) was increased (520 +/- 31 vs
      299 +/- 30 mcEq/L, +74%, P < .001), whereas value in obese patients (n = 18) vs
      that in obese control subjects (n = 11) was decreased (542 +/- 34 vs 774 +/- 62, 
      30%, P < .01). This opposite behavior of FFA in lean and obese patients needs to
      be confirmed. Data in this study seem to indicate that low TG value may be a
      precocious marker of autoimmunity or immune system hyperreactivity.

PMID- 14600657
TI  - Evaluating liver disease in chronic hepatitis C--the role of the liver biopsy.

PMID- 14600658
TI  - Prevalence of stool parasite in medical personnel: a report from a tertiary
      hospital in Thailand.

PMID- 14600659
TI  - MedGenMed Hematology/Oncology conference report--plenary session: from genes to
      cells to metastasis. Highlights from the 2003 annual meeting of the American
      Association for Cancer Research.

PMID- 14600660
TI  - Lessons from the developing world: obstructed labor and the vesico-vaginal
      fistula.

PMID- 14600662
TI  - Adult living donor liver transplantation.

PMID- 14600661
TI  - MedGenMed hematology/oncology conference report--dangerous liaisons: infections
      and cancer--time for a break-up? Highlights from the 2003 annual meeting of the
      American Association for Cancer Research; July 11-14, 2003; Washington, DC.

PMID- 14600663
TI  - A eulogy: personal reflections on Dr. Peter Safar.

PMID- 14600664
TI  - Medscape psychopharmacology today--do medications really expire?

PMID- 14600666
TI  - Case 1--a 65-year-old female patient presented to Kijabe Mission Hospital with a
      complaint of left thigh swelling.

PMID- 14600667
TI  - Geographic diseases--a new section in medscape general medicine.

PMID- 14600668
TI  - Technology in your practice: the electronic medical record: promises and
      pitfalls.

PMID- 14600669
TI  - Clinical cases in neurology from Johns Hopkins--case 3: 44-year-old man with
      fever, headache, confusion, and ataxia.

PMID- 14600670
TI  - MedGenMed Hematology/Oncology conference report--translational research: any
      danger lurking in its wake? Highlights from the 2003 annual meeting of the
      American Association for Cancer Research; July 11-14, 2003; Washington, DC.

PMID- 14600671
TI  - How should information about the effects of healthcare be presented?

PMID- 14600672
TI  - External breast prostheses: misinformation and false beliefs.
AB  - This article discusses common myths associated with the use of external breast
      prostheses and the impact this misinformation may have on the quality of life of
      women after mastectomy. A review of the literature reveals that very little
      research has been conducted on this subject. The majority of information on
      breast prostheses is provided by the manufacturers and tacitly accepted by
      healthcare providers and the media in general. Claims regarding the medical
      necessity of a weighted prosthesis and the suitability of gel fillings are
      examined and found wanting. Widespread acceptance of these myths may be
      preventing women from pursuing healthy lifestyle options and restricting the
      development of more suitable prosthetic products. The article concludes that a
      rigorous, evidence-based approach to the evaluation of external breast prostheses
      would enhance both the development of this noninvasive and cost-effective sector
      of post-mastectomy care, as well as the adjustment, well being and quality of
      life of breast cancer survivors.

PMID- 14600673
TI  - Remembering September 11, 2001: a global critical care community reaches out.

PMID- 14600674
TI  - Use of a condom to control massive postpartum hemorrhage.
AB  - OBJECTIVES: To evaluate the efficacy of a condom as a tamponade for intrauterine
      pressure to stop massive postpartum hemorrhage (PPH). DESIGN AND SETTING: This
      prospective study was done in the Obstetrics and Gynecology Department of Dhaka
      Medical College and Hospital, Bangladesh, between July 2001 and December 2002.
      PATIENTS: During the study period, 152 cases of PPH were identified; 109 were
      managed medically; 20 were managed using the B-Lynch procedure, and 23 were
      managed using the condom catheter. Patients were selected for intervention with
      the condom catheter when PPH that occurred as a result of atonicity or morbid
      adhesion (accreta) could not be controlled by uterotonics or a surgical
      procedure. In patients who were in shock due to massive hemorrhage, a condom
      catheter was introduced immediately without prior medical management.
      INTERVENTION: With aseptic precautions, a sterile rubber catheter fitted with a
      condom was introduced into the uterus. The condom was inflated with 250-500 mL
      normal saline, according to need. The condom catheter was kept for 24-48 hours,
      depending upon the initial intensity of blood loss, and gradually deflated when
      bleeding ceased. MAIN OUTCOME MEASURES: (1) Ability of condom catheter to stop
      bleeding; (2) time required to stop bleeding after the tamponade was applied; (3)
      subsequent morbidity in terms of severe infection, despite use of prophylactic
      antibiotics. RESULTS: In all 23 cases in which the condom catheter was used,
      bleeding stopped within 15 minutes. No patient needed further intervention. No
      patient went into irreversible shock. There was no intrauterine infection as
      documented by clinical signs and symptoms and culture and sensitivity of high
      vaginal swab. CONCLUSION: The hydrostatic condom catheter can control PPH quickly
      and effectively. It is simple to use, inexpensive, and safe. In developing
      countries where PPH remains a primary cause of maternal mortality, any healthcare
      provider involved in delivery may use this procedure for controlling massive PPH
      to save the lives of patients.

PMID- 14600675
TI  - A low-resource, simple method to treat postpartum hemorrhage.

PMID- 14600676
TI  - Pervasive clinical computing: visualization tools.

PMID- 14600677
TI  - Suicide survivors: tips for health professionals.

PMID- 14600678
TI  - Spongiform encephalopathies: a tale of cannibals, cattle, and prions.

PMID- 14600679
TI  - Praise for the new geographic diseases section.

PMID- 14600680
TI  - ACL injury and open physes in the young athlete.

PMID- 14600681
TI  - Memories of Kijabe--a response to the new geographic diseases section.

PMID- 14600682
TI  - Improving the mental/psychosocial health of US children and adolescents: outcomes
      and implementation strategies from the national KySS Summit.

PMID- 14600683
TI  - Endodontics in the era of evidence-based practice.

PMID- 14600684
TI  - Predictive value of clinical findings for temporomandibular joint effusion.
AB  - OBJECTIVE: The aim of this work was to evaluate the predictive value of clinical
      symptoms for magnetic resonance imaging (MRI) findings of temporomandibular joint
      (TMJ) effusion. STUDY DESIGN: Sixty-one patients with TMJ pain were assessed by
      means of a standardized clinical examination and MRI. A calibrated investigator
      evaluated the presence of 8 clinical indicators (predictors) of TMJ effusion
      (outcome variable). A logistic regression analysis was performed to detect
      significant associations between clinical symptoms and MRI findings of TMJ
      effusion. The accuracy of the final logit to predict effusion was compared with
      that derived from univariate analysis. RESULTS: A clinical examination based upon
      the assessment of pain in the TMJ with lateral palpation, with posterior
      palpation, during motion, and during maximum assisted opening, and the presence
      of click and crepitus sounds has an accuracy of 78.7% to predict TMJ effusion.
      Among the single clinical symptoms, the most reliable predictor of TMJ effusion
      is the presence of pain with lateral palpation (accuracy 76.2%; K =.525).
      CONCLUSION: The use of a multiple regression approach demonstrated that an
      extensive clinical assessment which considers 6 main indicators consents to
      predict accurately the presence of MRI TMJ effusion. Based on these findings, MRI
      assessment should be reserved for patients in which the exact disc-condyle
      relationship needs to be evaluated.

PMID- 14600685
TI  - Palatal rotation-advancement flap for delayed repair of oroantral fistula: a
      retrospective evaluation of 63 cases.
AB  - OBJECTIVE: To review our 17-year clinical experience with delayed oroantral
      fistula repair by palatal rotation-advancement flap, and to report its
      advantages, disadvantages, and complications. STUDY DESIGN: The records of 63
      patients with late oroantral fistula treated by palatal rotation-advancement flap
      from 1984 to 2002 were reviewed. Eleven had undergone unsuccessful closure with a
      buccal flap. Data recorded were patient age and sex, cause of fistula, signs and
      symptoms, interval from appearance of fistula to repair, fistula size,
      radiographic appearance, method of repair, and immediate and late complications.
      RESULTS: There were 35 women and 28 men aged 21 to 71 years (mean 50.3 years).
      Surgery was performed 3 months to 20 years after injury (mean 1.8 years). Twenty
      four patients had acute maxillary sinusitis and 39 had chronic sinusitis. The
      main causes of oroantral fistula were extraction of the second and first molars
      and pathological lesions within the sinus. Average fistula size was 2.3 cm x 1.6
      cm. Fifty-one repairs were preceded by Caldwell-Luc operation. All fistulas were
      successfully closed with the palatal rotation-advancement flap, with minimal
      complications on long-term follow-up. CONCLUSION: The palatal rotation
      advancement flap is recommended for the late repair of oroantral fistula owing to
      its good vascularization, excellent thickness and tissue bulk, and easy
      accessibility; it also allows for the maintenance of the vestibular-sulcus depth.
      It is particularly indicated in cases of unsuccessful buccal flap closure.

PMID- 14600686
TI  - Comparison of the effects of 2 doses of methylprednisolone on pain, swelling, and
      trismus after third molar surgery.
AB  - OBJECTIVE: The aim of this study was to compare the effects of intravenous
      administration of 1.5 mg/kg and 3 mg/kg of methylprednisolone sodium succinate
      (MP) on pain, swelling, and trismus after third molar surgery. STUDY DESIGN:
      Twenty-six healthy patients with symmetrically impacted mandibular third molars
      were included in this double-blind, cross-over study. Either 1.5 mg/kg or 3 mg/kg
      of MP was administered by intravenous route one hour prior to the first
      operation. At the second operation the other dose was applied. Trismus was
      determined by measuring maximum interincisal opening and facial swelling was
      evaluated using a tape measuring method. Pain was determined using visual
      analogue scale and recording the number of pain pills taken. RESULTS: There was
      no statistically significant difference in trismus, facial swelling, and pain
      between the two groups. CONCLUSION: No clinical benefit of the higher dose of MP
      was demonstrated.

PMID- 14600687
TI  - Management of oral surgery in patients with hereditary or acquired angioedemas:
      review and case report.
AB  - Angioedemas are a rare but significant event in simple oral surgery because they
      can cause an acute life-threatening laryngeal edema. We report a case of a tooth
      extraction in a patient with hereditary angioedema, for which the C1-inhibitor
      (C1-INH) concentration administered effectively controlled edema during and after
      extraction. We also review case reports of oral surgery management in patients
      with hereditary and acquired angioedemas. In 2 of 36 cases, laryngeal edema
      occurred after teeth extraction. One was considered to be a type 2 acquired
      angioedema, which tolerates replacement therapy with fresh frozen plasma. The
      other case was managed only with danazol, and it was suggested that this was on
      occasion insufficient. Safety of oral surgery on patients with angioedema depends
      on the type of angioedema and the availability of C1-INH concentration. An exact
      diagnosis of the type of angioedema is needed to know the effect of replacement
      therapy with C1-INH.

PMID- 14600688
TI  - Treatment of perioral dystonia with botulinum toxin in 4 cases of Meige's
      syndrome.
AB  - OBJECTIVE: We describe the treatment of 4 patients (median age, 53.5 years) with
      incapacitating perioral dystonia and insufficient response to peroral medication.
      Their general treatment with clonazepam and anticholinergics was supplemented by
      intramuscular injections with botulinum toxin A (20-40 U) in the orbicularis oris
      muscle, guided by electromyography (EMG). STUDY DESIGN: Perioral dystonia and
      treatment effect were assessed by using subjective global and visual analog
      scales, examiner-based video movement counts and rating scales, and quantitative
      EMG. t Tests were used for statistical analysis. RESULTS: The result of the
      intramuscular botulinum toxin A injections was characterized by the patients as
      "much improved"; correspondingly, dystonia was significantly reduced in visual
      analog scale scores, on examiner-based assessments, and in recordings of EMG. The
      side effects were few and short-lasting. CONCLUSION: Incapacitating perioral
      dystonia in Meige's syndrome may be safely controlled by recurrent EMG-guided
      botulinum toxin A injections in the orbicularis oris muscle, in combination with
      general medication.

PMID- 14600689
TI  - Allergic fungal sinusitis: report of 3 cases and review of the literature.
AB  - Allergic fungal sinusitis is a form of noninvasive fungal disease resulting from
      an IgE-mediated hypersensitivity reaction in atopic individuals. Allergic fungal
      sinusitis can present with a continuum of symptoms. Accumulation of allergic
      inspissated mucin may cause simple nasal obstruction or progress to facial
      deformity with osteolytic destruction and intracranial extension. Multiple
      species of fungi are now recognized as etiologic factors responsible for
      initiating the inflammatory response. This article discusses 3 cases involving
      Aspergillus and Curvularia species, and reviews diagnostic image findings,
      pathophysiology, and medical-surgical management of this increasingly common
      disease.

PMID- 14600690
TI  - Constitutional mutation of keratin 13 gene in familial white sponge nevus.
AB  - OBJECTIVE: We sought to investigate a novel mutation in the keratin genes assumed
      to be responsible for a familial case of oral white sponge nevus. PATIENTS AND
      METHODS: The affected family consisted of a 36-year-old woman, her 17-year-old
      daughter, and her 14-year-old son. Keratin 4 and 13 genes extracted from venous
      blood lymphocytes were amplified by using the polymerase chain reaction and
      directly sequenced. RESULTS: Sequencing analysis of the 3 patients revealed the
      presence of a novel heterozygous T-to-C transition mutation in exon 1 of the
      keratin 13 gene, with no abnormalities detected in the keratin 4 gene.
      CONCLUSION: We identified a novel heterozygous missense mutation at 332T>C in the
      keratin 13 gene believed to be related to the development of white sponge nevus.

PMID- 14600691
TI  - Immunohistochemical evaluation of cell proliferation antigen Ki-67 and apoptosis
      related proteins Bcl-2 and caspase-3 in oral granular cell tumor.
AB  - PURPOSE: We sought to evaluate the cell proliferation activity and
      immunohistochemical expression of proteins that promote or inhibit apoptosis in
      oral granular cell tumor (GCT). STUDY DESIGN: Immunohistochemistry for Ki-67, a
      cell proliferation marker; Bcl-2, an anti-apoptotic protein; and caspase-3, a
      protein implicated in the execution of apoptosis, was performed on tissues from
      12 patients with GCT of the tongue. RESULTS: Nuclear immunostaining for Ki-67 was
      observed only in isolated GCs (less than 2%). All patients exhibited cytoplasmic
      immunoreactivity for Bcl-2 in the majority of tumor cells. Cytoplasmic staining
      for caspase-3 was also present in more than 50% of GCs in all tumors.
      CONCLUSIONS: GCT cells display low proliferation activity, a finding possibly
      related to their benign behavior. Caspase-3 expression suggests activation of the
      apoptotic cascade in the GCs, but persistence of the cells in the tissues could
      be attributed to the expression of Bcl-2 protein, a molecule that functions as a
      survival factor.

PMID- 14600692
TI  - Mucocutaneous leishmaniasis in a US citizen.
AB  - Mucocutaneous leishmaniasis (MCL) is endemic to many areas of Central and South
      America. A case of MCL in a US citizen is reported here. An ulcer appeared on the
      patient's left hard palate, years after a working trip to Peru. Punch biopsies of
      the lesion were obtained, Leishmania promastigotes were isolated by culture and
      animal inoculation, and the patient was appropriately treated. As this case
      demonstrates, a patient's travel history is a key element in making a
      differential diagnosis of oral lesions.

PMID- 14600693
TI  - The effect of chlorhexidine as an endodontic disinfectant.
AB  - OBJECTIVE: The purpose of this study was to establish whether addition of a 2%
      chlorhexidine rinse to a conventional treatment protocol enhances the rate of the
      successful disinfection of the root canal system in vivo. STUDY DESIGN: Twenty
      four teeth with infected necrotic pulps and resorbing apical periodontitis were
      treated with a conventional technique in which 1% NaOCl as irrigant was used.
      Half of the cases received an additional rinse with 2% chlorhexidine. Prereduced
      thioglycollate medium was used to take cultures that were incubated for 4 weeks.
      RESULTS: Cultivable bacteria were retrieved at the conclusion of the first visit
      in 1 out of 12 chlorhexidine cases whereas in the control group 7 out of 12 cases
      showed growth. This difference was significant (P < .05). CONCLUSION: The
      findings are clinically important.

PMID- 14600694
TI  - Twelve-year follow-up of an autogenous mandibular canine transplant.
AB  - Transplantation is the transfer of tissue or an organ from 1 site to another in
      the same person or between different persons. A transplantation in which donor
      and recipient are the same individual has been termed autogenous transplantation,
      autoplastic transplantation, or autotransplantation. The purpose of this report
      was to describe a patient undergoing autotransplantation of an impacted
      mandibular canine to its normal position in the mandible and the 12-year follow
      up. Five years after the surgical procedure, the patient presented with pulp
      canal obliteration in the autotransplanted tooth. Twelve years after the
      autotransplantation, the tooth position was stable despite pulp canal
      obliteration, but with no sign of inflammatory resorption or a periapical lesion.
      In addition, there was no sign of replacement resorption (ankylosis). The
      endodontic literature has shown that the prognosis of patients undergoing
      autotransplantation may be good under specific considerations. Therefore, the
      technique may be a treatment plan option for the replacement of missing teeth.

PMID- 14600696
TI  - Smear layer production by 3 rotary reamers with different cutting blade designs
      in straight root canals: a scanning electron microscopic study.
AB  - OBJECTIVES: The design of the cutting blade of rotary instruments may affect the
      outcome of root canal instrumentation in terms of cleanliness. The aim of this
      scanning electron microscopic study was to compare the quality and amount of
      smear layer generated in the apical third of straight root canals by 2 rotary
      nickel-titanium reamers and 1 rotary steel reamer with different cutting blade
      designs. STUDY DESIGN: Seventy intact, single-rooted human mandibular premolars
      with straight, fully developed roots were selected for this study. Before
      instrumentation, the cervical portion of all teeth was removed by using a
      microtome (Isomet), leaving 13-mm-long roots. Automated preparation was performed
      with ProFile (n = 20) and Hero 642 (n = 20) reamers by using the crown-down
      technique and with a stainless steel engine reamer (Mani; n = 20) by using a
      reaming motion. All root canals were instrumented to No. 40. A control group
      (pulp extirpation with barbed broaches; n = 10) was also included. Irrigation
      with 3 mL of a 1% sodium hypochlorite (NaOCl) solution was performed after each
      instrumentation. After the instrumentation, each root was split longitudinally,
      and a scanning electron microscope was used to examine the selected areas of the
      canal walls at the apical third from 2 different perspectives. A 4-category
      scoring system for smear layer was used, and the resulting scores were
      statistically analyzed. RESULTS: The least smear layer remained in the Hero 642
      group at the selected apical third of straight root canals (P < .05). However,
      all instruments left a smear layer. The surface texture of the smear layer, in
      addition to the depth and the frequency of packed materials into the dentinal
      tubules, varied with instrument type. CONCLUSION: These data revealed that the
      design of the cutting blade of rotary instruments can affect root canal
      cleanliness in straight root canals. This information may be useful in the
      selection of nickel-titanium rotary reamers.

PMID- 14600695
TI  - Direct capping of human pulps with a dentin bonding system or with calcium
      hydroxide cement.
AB  - OBJECTIVE: To study human pulp reactions to direct cappings with a dentin
      adhesive compared with a calcium hydroxide cement, especially with respect to
      formation of hard tissue in the exposure site. STUDY DESIGN: Direct pulp cappings
      were made in 34 caries-free premolars scheduled for extraction due to orthodontic
      treatment. Half of the teeth were capped with a dentin adhesive, the other half
      with a calcium hydroxide cement. After periods of from 7 to 70 days, the teeth
      were extracted and processed for light microscopical examination. RESULTS: No
      postoperative sensitivity was experienced. A slight inflammatory reaction was
      seen in both groups in the short observation period. In the long observation
      period, significantly more "dentin bridging" was seen in the calcium hydroxide
      group than in the dentin adhesive group (P < .05). CONCLUSION: The findings from
      the present limited material is in accordance with previous findings from human
      studies and contraindicate use of dentin adhesives for direct pulp capping.

PMID- 14600697
TI  - Tissue-dissolution capacity and dentin-disinfecting potential of calcium
      hydroxide mixed with irrigating solutions.
AB  - OBJECTIVE: The goal of this study was to compare the tissue-dissolution potential
      and antibacterial effectiveness of a conventional Ca(OH)(2)/saline paste with
      equivalent Ca(OH)(2)/NaOCl and Ca(OH)(2)/chlorhexidine digluconate medications.
      STUDY DESIGN: Tissue specimens were obtained from freshly dissected pig palates.
      Tissue pieces of similar form and weight were incubated in air-tight containers
      with Ca(OH)(2) pastes or solutions proper for up to 7 days. Antimicrobial testing
      was performed in dentin blocks infected with Enterococcus faecalis. Medicated,
      sealed dentin specimens were incubated for 1 and 5 days, and bacterial growth was
      tested at different dentin depths. RESULTS: Up to day 4, the Ca(OH)(2)/irrigating
      solution mixtures dissolved tissue more effectively than the conventional
      Ca(OH)(2)/saline paste. After 7 days, however, no statistically significant
      differences were found between the saline and hypochlorite mixtures, but the
      Ca(OH)(2)/chlorhexidine medication was significantly less effective. Dentin block
      disinfection was quicker and more thorough with the Ca(OH)(2)/chlorhexidine or
      the Ca(OH)(2)/NaOCl than with the Ca(OH)(2)/saline paste. CONCLUSION:
      Ca(OH)(2)/irrigant mixtures under investigation appear more advantageous than the
      conventional Ca(OH)(2)/saline mixture, and merit further investigation in a
      clinical study.

PMID- 14600698
TI  - Evaluation of canal cleanliness and smear layer removal after the use of the
      Quantec-E irrigation system and syringe: a comparative scanning electron
      microscope study.
AB  - OBJECTIVE: The purpose of this study was to evaluate canal cleanliness and smear
      layer removal after use of the Quantec-E irrigation system and to compare the
      system with traditional irrigation. STUDY DESIGN: Forty anterior teeth were
      randomly assigned to 4 groups. Group A consisted of 15 teeth that were
      instrumented with .12, .10, .08, .06 and .04 tapered rotaries while
      simultaneously irrigated via the Quantec-E irrigation pump with 12 mL of 5.25%
      NaOCl, followed by 6 mL EDTA 17% in crown-down fashion, with a final flush with 4
      mL 5.25% NaOCl. Group B consisted of 15 teeth that were instrumented with the
      same instrument sequence, and irrigated with the same volumes via traditional
      needle and syringe. Group C consisted of 5 teeth that were sectioned and examined
      under a scanning electron microscope (SEM) without any instrumentation and served
      as a negative control. Group D consisted of 5 teeth that were instrumented dry,
      without any irrigation, and served as a positive control. All teeth were
      sectioned buccolingually and examined with SEM at 700x magnification in the
      apical, middle, and coronal portions of the canals. Analysis of SEM images was
      performed by 5 independent examiners using a 4-point scoring system. RESULTS:
      Irrigation with the Quantec-E irrigation pump resulted in cleaner canal walls,
      less debris, and more complete removal of the smear layer within the coronal one
      third, when compared with syringe irrigation. However, no difference was observed
      in the middle and apical one thirds of the root canal. CONCLUSION: There was no
      significant difference between the 2 irrigation systems.

PMID- 14600699
TI  - Efficacy of chlorhexidine- and calcium hydroxide-containing medicaments against
      Enterococcus faecalis in vitro.
AB  - OBJECTIVE: We sought to assess the efficacy of chlorhexidine (CHX) and calcium
      hydroxide, Ca(OH)(2), against Enterococcus faecalis in vitro. STUDY DESIGN: The
      effect of CHX (0.2% and 2% in gel or solution) and Ca(OH)(2) (alone or with 0.2%
      CHX gel) was evaluated by using the agar diffusion test and an in vitro human
      root inoculation method, to measure zone of inhibition or bacterial growth with
      optical density analysis, respectively. For optical density analysis, samples
      from infected root canals were collected after 7 days of medication and were
      cultured for 24 hours in brain-heart infusion to detect viable bacteria. RESULTS:
      In the agar diffusion test, CHX was effective against E faecalis in a
      concentration-dependent fashion, but Ca(OH)(2) alone had no effect. In the root
      canal inoculation test, CHX was significantly more effective against E faecalis
      than Ca(OH)(2) was (P < .05), but there were no significant differences between
      the modes of medication or concentrations of CHX. CONCLUSIONS: CHX is effective
      against E faecalis in vitro. Further in vivo studies are needed to confirm the
      value of CHX in clinical treatment.

PMID- 14600700
TI  - Ultrasound identification and quantitative measurement of blood supply to the
      anterior part of the mandible.
AB  - OBJECTIVE: Recent studies suggest that the main blood supply to the bony chin may
      be through a single arterial branch of the 2 sublingual arteries that anastomose
      at the midline and penetrate the bone through the lingual foramen, approximately
      13 mm from the lower border of the mandible. The objective of this study was to
      demonstrate the validity of this hypothesis in vivo, to identify clinically the
      main blood supply to the bony chin, and to measure its parameters: diameter of
      vessel, direction of flow, and its volume. Materials and method
      Ultrasound/doppler measurements and periapical radiographs were taken on 20
      healthy volunteers, randomly divided into 2 equal groups in order to compare the
      method's validity. In the first group, the lingual foramen was identified on
      periapical radiographs and then ultrasound/doppler measurements were performed.
      In the second group, this procedure was reversed. RESULTS: Positive
      identification of the lingual foramina on the periapical radiograph was obtained
      in 13 subjects compared to 20 subjects by ultrasound/doppler examination. Blood
      volume measurements were obtained in only 17 subjects. The diameter of the artery
      was 0.18-1.8 mm and the blood flow from 0.7-3.7 mL/min. CONCLUSIONS:
      Ultrasound/doppler imaging is a reliable method to visualize and measure the
      blood supply to the bony chin. It can become an important tool in presurgical
      assessment of patients who undergo genioplastic procedures, vestibuloplasty, or
      insertion of dental implants.

PMID- 14600701
TI  - Use of advanced imaging modalities for the differential diagnosis of pathoses
      mimicking temporomandibular disorders.
AB  - The medical records of 3 patients who visited our hospital with preauricular pain
      and limited jaw movement were retrospectively reviewed. All were clinically
      evaluated, diagnosed through the use of conventional radiographs, and initially
      treated as having temporomandibular disorders (TMD). However, their symptoms did
      not improve and even increased or facial swelling occurred, so advanced imaging
      modalities were used to make a differential diagnosis. The final diagnoses of the
      patients were cellulitis, an inflammatory pseudotumor, and pigmented villonodular
      synovitis. In addition to these 3 patients, 50 others who were initially
      misdiagnosed during a clinical examination as having TMD on conventional
      radiographs were reviewed in the English-language literature. When diagnosing
      patients with TMD symptoms, we must consider the possibility of unusual causes,
      including tumors and infections or inflammations. Furthermore, in addition to
      usual TMD treatment procedures, an advanced radiologic examination should be
      performed to aid in the differential diagnosis of all patients with unceasing
      pain and mouth-opening limitation.

PMID- 14600702
TI  - Preoperative assessment of the relationship between the mandibular third molar
      and the mandibular canal by axial computed tomography with coronal and sagittal
      reconstruction.
AB  - OBJECTIVE: We sought to evaluate the relationship between the mandibular third
      molar and the mandibular canal by using axial computed tomography with coronal
      and sagittal reconstruction for third molar surgery. STUDY DESIGN: Forty-seven
      impacted third molars in 41 patients were found in close association with the
      mandibular canal during a panoramic radiographic assessment. The relationship
      between the mandibular third molar and the mandibular canal was evaluated by
      using computed tomography and compared in terms of operative exposure of the
      inferior alveolar nerve and postoperative labial dysesthesia. RESULTS: Twenty
      four (51%) mandibular canals were buccal relative to the third molar, 12 were
      lingual, 9 were inferior, and 2 were between roots. At the time of the surgical
      procedure, the inferior alveolar nerve was visible in 7 patients. Postoperative
      lower lip dysesthesia occurred in 1 patient whose mandibular canal was in the
      lingual position. CONCLUSIONS: Axial computed tomography with coronal and
      sagittal reconstruction provides useful information to surgeons regarding the
      relationship between the mandibular third molar and the mandibular canal.

PMID- 14600704
TI  - [Life as a gift and a merchandise].

PMID- 14600703
TI  - Evaluation of calcified carotid artery atheromas detected by panoramic radiograph
      among 80-year-olds.
AB  - OBJECTIVE: To evaluate the incidence among 80-year-olds of calcified carotid
      artery atheromas (CCAAs) as detected on panoramic radiographs. The relationship
      between CCAAs and general and oral health was also evaluated. STUDY DESIGN: Six
      hundred and fifty-nine panoramic radiographs (262 males, 397 females), obtained
      from 80-year-old residents of Fukuoka Prefecture, Japan, were used for evaluation
      of CCAAs. RESULTS: Of 659 panoramic radiographs, 33 (5%) were noted to have
      CCAAs. These appeared as a radiopaque nodular mass or masses adjacent to or just
      below the intervertebral space between C3 and C4. CCAAs were found in 8 males and
      25 females. There were marginally significant differences between males and
      females in CCAAs (P = 0.06). Seventy-four percent of CCAAs were detected in the
      right side. There appeared to be very little relationship between CCAAs and
      general and oral health. CONCLUSIONS: The results of this study gives further
      support to the idea of using panoramic radiographs to detect CCAAs. Therefore, we
      feel that panoramic radiographs should be evaluated not only for pathosis of the
      teeth and jaws, but also for other incidental findings, especially in the soft
      tissue region of the neck. The findings from this study provide potentially life
      saving information especially for those elderly people who are at risk for
      stroke.

PMID- 14600705
TI  - [Is the ordering/purchasing-executing model useful?].

PMID- 14600706
TI  - [Back pain patients in from the cold].

PMID- 14600707
TI  - [Alcohol drinking habits].

PMID- 14600708
TI  - [Alcohol consumption, income and education in Norway, 1993-2000].
AB  - BACKGROUND: We have studied the trend in alcohol consumption by socio-economic
      status in Norway over the 1993-2000 period. Have differences in consumption been
      stable over time, or have they levelled off? MATERIAL AND METHODS: Our analysis
      is based on self-reported data from 6894 persons, stratified by year, sex, age,
      level of education, level of income, and where in Norway they lived. Bivariate
      and multiple analyses were performed. RESULTS: Alcohol consumption increased in
      all socio-economic groups over this period. Men consumed more than women;
      consumption increased with level of education and level of income. Income and
      level of education predicted alcohol consumption about equally well. The Oslo
      area had the highest consumption. INTERPRETATION: Alcohol consumption has
      increased in all socio-economic groups. It increases with level of education and
      higher income; men consume more than women.

PMID- 14600709
TI  - [Occurrence of musculoskeletal complaints in Hordaland].
AB  - BACKGROUND: Musculoskeletal complaints are widespread and a major public health
      problem in western countries. Prevention and treatment are challenges because the
      aetiologic factors are not fully understood. Our objective was to estimate the
      prevalence of and identify possible risk factors for musculoskeletal complaints.
      MATERIAL AND METHODS: A cross-sectional study including 11 566 men and 13 660
      women aged 40-49 and 70-74 who completed a questionnaire in the Hordaland Health
      Study 1997-99. RESULTS: Musculoskeletal pain and/or stiffness lasting at least
      three months during the past year was reported by 4461 men (39 %) and 6713 women
      (49 %). Prevalence among women increased with age. Musculoskeletal complaints
      were associated with low educational attainment and smoking among both men and
      women 40-49 years old, and with high body mass index and low physical activity
      among women. Among the 70-74-year-olds, complaints were associated with low
      educational attainment among men and with smoking, high body mass index and low
      physical activity among women. A dose-response relationship between smoking and
      musculoskeletal complaints was found, with a stronger effect among women than
      men. INTERPRETATION: Musculoskeletal complaints were common, the prevalence
      higher among women than men. The results indicate that musculoskeletal complaints
      may be prevented or reduced by smoking cessation.

PMID- 14600710
TI  - [Colorectal cancer in general practice--what is the benefit of testing for occult
      blood in feces?].
AB  - BACKGROUND: We wanted to examine the extent and value of testing in a general
      practice for occult blood in faeces in patients suspected of having colorectal
      cancer. MATERIAL: All patients treated for colorectal cancer in the surgical
      department in the district hospital 1985-98 were registered (n = 880) and names
      compared to the files in a general practice in Arendal. The files of our patients
      were examined in order to determine patients' and doctor's delay in diagnosing
      the disease and whether testing of occult blood in faeces was used in the
      examination. In addition, all patients in the practice tested with occult blood
      in faeces (Hemofec) 1985-94 were noted (n = 962) and the files of 20 % of them
      examined. RESULTS: The five general practitioners in our practice were
      responsible for diagnosing 74 of the patients with verified colorectal cancer
      (approx. one new patient per doctor per year). Patients' mean delay was 1.7
      months (median 1.1), doctor's delay mean 1.8 months (median 0.9). In 25 patients
      the examination of occult blood in faeces was part of the diagnostic workup. 20
      of the patients tested positively, five negatively. In 71%, the reason for
      testing was non-specific abdominal symptoms. Among these patients, 11% tested
      positively and 89% negatively. INTERPRETATION: Examination of occult blood in
      faeces has a limited role to play in the diagnosing of colorectal cancer, though
      a negative result is valuable in order to exclude colorectal cancer in patients
      with non-specific abdominal complaints and thus prevent unnecessary use of
      colonoscopy.

PMID- 14600711
TI  - [Neuroleptic malignant syndrome in a patient treated with olanzapine].
AB  - BACKGROUND: Neuroleptic malignant syndrome is a potentially fatal reaction to
      antipsychotic drugs, characterised by hyperthermia, rigidity, autonomic
      instability and muscle injury. The syndrome was originally associated with
      traditional neuroleptics, but may also occur during treatment with second
      generation atypical antipsychotic drugs. MATERIAL AND METHODS: We present a case
      of neuroleptic malignant syndrome in a 52-year-old patient who had been treated
      for 2(1/2) years with olanzapine, a new atypical antipsychotic agent. He had
      previously been treated with a conventional neuroleptic for 25 years. RESULTS:
      For 2-3 days the patient's condition was serious and unstable, requiring care in
      the emergency unit. When he was discharged after 12 days' hospitalisation, he was
      still physically disabled and needed care in his home. INTERPRETATION:
      Neuroleptic malignant syndrome may develop even after long and stable treatment
      with atypical antipsychotic agents. The condition should be suspected in
      psychiatric patients who present with unclear hyperthermia and muscular rigidity.
      Essential therapeutic principles are cooling, rehydration, correction of
      electrolytic disturbances, cardiac monitoring, regular tests of renal function
      and creatine kinase. Treatment of malign hyperthermia with dantrolene should also
      be considered.

PMID- 14600712
TI  - [Meningitis associated with reactivation of varicella-zoster virus].
AB  - BACKGROUND: Reactivation of varicella-zostervirus (VZV) can manifest as infection
      of the central nervous system. The detection of VZV DNA in cerebrospinal fluid by
      polymerase chain reaction has extended our knowledge about the frequency of
      various clinical manifestations in the immunocompetent host, also without the
      typical rash of shingles. MATERIAL AND METHODS: Over a period of three years,
      1999 through 2001, we performed VZV polymerase chain reaction in cerebrospinal
      fluid in 364 patients with suspected infection of the central nervous system.
      RESULTS: We detected VZV DNA in the cerebrospinal fluid in five patients. Four of
      the patients had reactivated VZV infection. Meningitis was seen in two young
      immunocompetent individuals; one of them without shingles. One patient had
      myelitis without shingles and one had zoster radiculitis. One patient was a child
      with encephalitis and primary infection. INTERPRETATION: Our results are similar
      to results from other investigators that have found VZV DNA in the cerebrospinal
      fluid in immunocompetent patients with meningitis or encephalitis as the most
      common clinical manifestation, with or without shingles.

PMID- 14600713
TI  - [Drug therapy in secondary prophylaxis after transient cerebral ischemia or
      cerebral infarction].
AB  - BACKGROUND: Stroke is the third leading cause of death in western countries and
      the leading cause of dependence in activities of daily living. Efforts to reduce
      its prevalence should therefore be given the highest priority. Uncertainty
      prevails as to the significance of the various types of intervention. METHODS:
      This review is based on personal experience, though mostly on a search for
      relevant literature in the Cochrane Library. RESULTS: Important measures are
      treatment of hypertension with target area 140/90 mm Hg, anticoagulation in
      patients with atrial fibrillation and other potential sources of cardioemboli,
      and for the remainder antiplatelet agents in the form of acetylsalicylic acid,
      probably preferably combined with dipyradimole. One should also consider drugs
      reducing serum lipids. INTERPRETATION: Adequate secondary prophylaxis after
      transient ischaemic attack (TIA) or ischaemic stroke is of potential great
      benefit in reducing the incidence of new stroke, myocardial infarction or
      premature vascular death. Standardised guidelines may facilitate implementation
      of these measures, if they are regularly updated and adjusted to the needs of the
      individual patient.

PMID- 14600714
TI  - [Gout and hyperuricaemia--should both be treated?].
AB  - Patients with increased levels of uric acid will usually be treated with drugs if
      symptoms of acute arthritis or kidney stones occur. Drugs for the treatment of
      acute arthritis attacks include non-steroidal anti-inflammatory drugs (NSAIDs),
      glucocorticoids systematically or injected into the joint, and colchicine. As
      prophylactic long-term treatment of recurring attacks, allopurinol, probenicide
      and colchicine are therapeutic alternatives. There is still no consensus on the
      treatment of individuals with asymptomatic hyperuricaemia.

PMID- 14600715
TI  - [Clinical examination of the pelvis in patients with multiple traumas is
      unreliable].
AB  - BACKGROUND: The primary examination of a seriously injured patient is often done
      according to the Advanced Trauma Life Support concept. This concept calls for
      routine x-rays of the chest, pelvis and cervical spine. We have seen a tendency
      in Norway towards selective use of the pelvic film according to trauma mechanism
      and physical findings, even in patients with multiple traumas. MATERIAL AND
      METHODS: Four cases illustrate the risk of missing serious injuries in patients
      with multiple injuries if routine pelvic x-ray is omitted. A review of the
      literature confirms that routine pelvic x-ray may be omitted only if the patient
      is alert, has a negative physical pelvic examination, and no other distracting
      painful injuries. INTERPRETATION: Early x-ray of the pelvis should still be a
      routine in patients with multiple injuries, but may be omitted in patients with
      normal consciousness, no distracting painful injuries and no pain on examination
      of the pelvis.

PMID- 14600716
TI  - [Elective stent treatment of abdominal aortic aneurysm].
AB  - BACKGROUND: First described in 1991, endovascular treatment is a simplified
      method for abdominal aortic aneurysm repair (EVAR). The enthusiasm created by few
      complications and early mobilisation was replaced by scepticism because of the
      high frequency of secondary complications such as endoleak, stenosis, graft
      migration, aneurysm enlargement and late rupture. Though the method still is
      considered experimental, thousands of grafts are inserted every year. MATERIAL
      AND METHODS: From 1998, 53 patients underwent EVAR electively at our institution,
      17 of whom were for medical reasons considered inoperable in open surgery. They
      were followed up with CT scans, which together with angiograms were evaluated
      retrospectively. Co-morbidity and complications were registered. Follow up was at
      26 (4-50) months for 49 patients. RESULTS: Two patients died. There were two
      other complications in addition to two superficial wound infections. There were
      no surgical conversions. 18 patients had 25 secondary interventions. Cumulative
      intervention rate was 25% after 12 months, 28% after 24 months and 53% after 36
      months. Four stenoses were seen the first 6 months. 19 patients had an endoleak
      (1 had type I after 24 months, 6 had type II endoleak, 5 had type III endoleak of
      which two appeared after 3 years). Graft migration was observed in 9 patients (5
      at 3 years control). Two ruptures were corrected with endovascular technique.
      Survival and interventions were equal among inoperable and operable patients.
      INTERPRETATION: Few early complications are overshadowed by the frequent and
      unpredictable late complications after EVAR; patients have to be followed up for
      years. For patients unfit for open surgery this is, however, an optional
      treatment if intervention is otherwise indicated.

PMID- 14600717
TI  - [Surgical treatment of Morton's neuroma].
AB  - BACKGROUND: We have resected the nerve when surgery is indicated for Morton's
      neuroma and wanted to compare our results with results reported after
      decompression. MATERIAL AND METHODS: 33 patients with 37 operated feet filled in
      a questionnaire 17 (8-27) months after surgery. They were asked to indicate their
      pain on a visual analogue scale (VAS: 0 = no pain, 100 = worst imaginable pain).
      RESULTS: Patients' mean age was 44 (17-76) at the time of operation. The average
      VAS score for pain was 81 (35-100) before operation and 7 (0-52) at review. 28
      said the pain had disappeared (VAS 0). CONCLUSION: Three quarters of our patients
      had no pain at review. This is comparable to reported results after
      decompression.

PMID- 14600718
TI  - [Drugs and porphyria].

PMID- 14600719
TI  - [Multidisciplinary outpatient clinics for back pain patients--a new treatment
      program].
AB  - Chronic low back pain (LBP) represents a major health problem, especially in
      Western Europe and North America. The aim of this study is to give an account of
      why a multidisciplinary treatment program in an outpatient spine clinic is the
      best treatment for many sub-acute and chronic LBP patients on long-term sick
      leave. We present an overview of documented treatment effects from
      multidisciplinary treatment programmes, an outline of the treatment in an
      outpatient spine clinic, and an account of why multidisciplinary programs are
      beneficial. The treatment of this patient group is also shown to be cost
      effective when one differentiates between light and extensive multidisciplinary
      programmes. A future challenge rests in the fact that even after optimal
      treatment, approximately 20 % of patients still do not return to work.

PMID- 14600720
TI  - [Should prioritization in health care programs be based on duty or care ethics or
      benefit ethics?].

PMID- 14600721
TI  - [Inter-collegial guidance after completed specialty training].

PMID- 14600722
TI  - [Ragnhild Emblem. With a heart for research and an eye for the clinic].

PMID- 14600723
TI  - [Heart transplantation--20 years after].

PMID- 14600724
TI  - [Medical research--money or life?].

PMID- 14600726
TI  - [Clinical leadership and academic competence].

PMID- 14600727
TI  - [Adverse effects--making nail soup].

PMID- 14600728
TI  - [Sexual abuse of children].

PMID- 14600731
TI  - [Is sick leave mostly frequent among those with best resources?].

PMID- 14600732
TI  - [Acupuncture during labor can reduce the use of pethidine].

PMID- 14600733
TI  - [Medical certificate for elderly automobile drivers].

PMID- 14600735
TI  - [Ethical limitations and limitations of naivety].

PMID- 14600736
TI  - [Rare infections new challenges].

PMID- 14600737
TI  - ["Just" a headache--a big torment].

PMID- 14600738
TI  - [Congenital malformations in children born after assisted fertilization in
      Norway].
AB  - The aim of this study was to compare the prevalence at birth of birth defects in
      children born after intracytoplasmatic sperm injection (ICSI) and children born
      after traditional in vitro fertilisation (IVF). Altogether 553 children were born
      after ICSI treatment in Norway during the period 1996-1998 (351 singletons, 95
      twins-pairs and 4 triplets) while 1731 were born after IVF treatment (1004
      singletons, 344 sets of twins and 13 triplets). Birth defects were registered in
      5.42% of children born after ICSI and in 5.14% of children born after IVF; 3,07%
      and 3.00% respectively were major birth defects. We conclude that
      intracytoplasmic sperm injection does not imply a significant increase in the
      prevalence at birth of birth defects compared to children conceived by
      traditional IVF.

PMID- 14600739
TI  - [Cervicogenic headache].
AB  - BACKGROUND: Cervicogenic headache means headache caused by a dysfunction in the
      neck. MATERIAL AND METHODS: The review is based on the authors' experience and a
      systematic search in Medline. RESULTS AND INTERPRETATION: Various anatomical
      structures may be responsible for cervicogenic headache, i.e. the vertebral
      artery or its surrounding sympathetic nerve plexus, spinal nerve roots,
      intervertebral discs and facet joints in the cervical spine.

PMID- 14600740
TI  - [Brucellosis--a rare zoonosis].
AB  - BACKGROUND: Brucellosis is a rare infectious disease in Norway. MATERIAL AND
      METHODS: We present a patient admitted to the department of medicine at
      Haraldsplass Hospital, Bergen and give a review of the epidemiology, symptoms,
      diagnosis and treatment of Brucellosis. RESULTS AND INTERPRETATION: The clinical
      picture of Brucellosis is often non-specific, with swings in fever, general
      malaise and myalgia. Complications such as osteomyelitis, endocarditis and
      coagulase-negative staphylococcus (CNS) infection occur in rare cases. The
      diagnosis is established by detection of Brucella species in blood cultures or
      tissue aspirate. Brucella is often difficult to isolate, but the available
      serological tests are highly sensitive and specific. The infection is treated
      with long-term administration of a combination of two appropriate antibiotic
      drugs. Surgery may be necessary in case of serious complications. If adequately
      treated, Brucellosis has a good overall prognosis.

PMID- 14600741
TI  - [Treatment of psychologically traumatised patients in Norway].
AB  - BACKGROUND: The Norwegian Directorate of Health and Social Affairs is carrying
      out a project on various aspects of traumatic stress. The present survey was
      carried out in 2001 in order to gather more knowledge about these patients within
      the mental health care system. MATERIAL AND METHODS: 325 hospitals, outpatient
      clinics and district psychiatric centres were asked by questionnaire to comment
      on the types of traumatised patients they treated, their own perceived
      professional skills, the diagnoses they used and the therapy they offered, and
      their contact with national and regional specialist units. RESULTS: Refugees and
      victims of sexual abuse were the groups treated by most units; only a few treated
      veterans of UN/NATO peacekeeping forces. Half of the units reported lack of
      professional skills in treating refugees. Only a few units reported changes in
      diagnosis and treatment as a result of advice from the specialist units.
      INTERPRETATION: The high frequency of units reporting a need for better skills in
      treating refugees is a challenge to the mental health care system and the
      specialist units. The results suggest a need for discussion of the role of the
      national and regional specialist units as well as a need for closer cooperation
      between psychiatric and primary health care.

PMID- 14600742
TI  - [Mobile ultrasonography in a medical department].
AB  - BACKGROUND: We examined the usefulness and image quality of a mobile miniaturised
      ultrasound scanner in a medical ward. MATERIAL AND METHODS: The instrument
      (SonoSite 180), weighing 2.4 kg, is a hand-carried system powered by batteries.
      In 25 days we recruited consecutively 36 patients aged 23-92. Four different
      operators evaluated the use of the scanner. We examined one group of patients
      with relatively simple diagnostic challenges (e.g. gallbladder stone) and one
      group of patients demanding more advanced visualisation (e.g. peptic ulcer,
      colitis). RESULTS: The scanner was easy to carry around and scanning was
      initiated in 10 seconds. We found satisfactory image quality on 81% of the
      examinations, despite the fact that in 28% of cases, bowel air and abdominal fat
      impaired acoustic penetration. Average scanning time was 7 +/- 3 minutes. In 83%
      of cases, mobile scanning adequately solved the clinical problem. Diagnostic work
      up or treatment was changed because of scanning in 39% of the patients. In 64% of
      cases, standard-procedure referral to the department of radiology was avoided. In
      81% of the examinations the operator was very satisfied with the scanner, also in
      cases that required advanced visualisation. INTERPRETATION: This mobile scanner
      was simple to use and gave quick results in a medical ward. The operators were
      very satisfied: mobile scanning changed diagnostic work-up or treatment in 4 out
      of 10 cases. Mobile ultrasound scanning enables early diagnosis and seems to
      promote an efficient flow of patients in a hospital unit.

PMID- 14600743
TI  - [Intractable postpartum haemorrhage treated with selective arterial
      embolization].
AB  - BACKGROUND: Postpartum haemorrhage is a major contributor to maternal morbidity
      and mortality. MATERIAL AND METHODS: In this case report we present a patient
      with intractable postpartum haemorrhage, successfully treated with selective
      arterial embolisation of the uterine arteries. RESULTS AND INTERPRETATION: In
      most cases, primary postpartum haemorrhage can be managed with conservative
      treatment involving uterine massage, uterotonic drugs and uterine/vaginal
      packing. With persistent bleeding, vascular ligation or hysterectomy may be
      needed. Surgical treatment may be technically difficult and may fail to control
      haemorrhage. For these reasons, selective arterial embolisation of the uterine
      arteries represents an interesting alternative that allows preservation of future
      fertility.

PMID- 14600744
TI  - [Fluticasone versus beclomethasone or budesonide in asthma].

PMID- 14600745
TI  - [Inhalation anti-asthmatic agents--efficient in chronic obstructive pulmonary
      disease?].

PMID- 14600747
TI  - [Genetic aspects of migraine].
AB  - BACKGROUND, MATERIAL AND METHODS: On the basis of studies identified by Medline
      and PubMed searches, this review focuses on the genetics of migraine. RESULTS:
      Compared to the general population, first-degree relatives of probands with
      migraine without aura (MO) have a two-fold risk of MO, whereas first-degree
      relatives of probands with migraine with aura (MA) have a four-fold increased
      risk of MA. Population-based family and twin studies have shown that migraines
      with or without aura have a multifactorial inheritance. In patients with familial
      hemiplegic migraine, a rare variant, a mutated gene encoding a subunit of a brain
      specific calcium channel in cell membranes has been found (CACNA1A). This gene
      may be of importance in the common forms of migraine in a few families and, at
      least in part, migraine may be a genetically determined channelopathy. However,
      migraine has also been linked to other genes with other functions, which makes
      the picture less clear. INTERPRETATION: It is to be hoped that in the next few
      years much more will be known about the molecular genetic mechanisms of migraines
      with and without aura. No gene is as yet defined.

PMID- 14600746
TI  - [Multiple sclerosis--a disease with complex genetics].
AB  - BACKGROUND: Multiple sclerosis (MS) is an inflammatory disease of the central
      nervous system, characterised by demyelinisation, gliosis and various degrees of
      axonal damage. The cause of the disease is unknown though there is evidence that
      MS is an immune mediated disease in which genetic, environmental and stochastic
      factors are involved. MATERIAL AND METHODS: Evidence of genetic influence in MS
      is reviewed. RESULTS: About 20% of patients have other family members with MS.
      First-degree relatives of MS patients have increased risk (2-5%) of developing MS
      compared to the risk in the general population (0.1%). The concordance rate in
      monozygotic twins (25-30%) is higher than in dizygotic twins (2-5%). Genetic
      analysis has shown association and linkage of MS to the HLA-DR2, DQ6 haplotype.
      Genome-wide screens have shown chromosome regions of potential importance.
      CONCLUSION: MS is a complex disease in which several genes are involved. Despite
      extensive candidate gene studies and genome-wide linkage screens, the HLA-DR2,
      DQ6 haplotype is the only genetic region that has shown unequivocal association
      and linkage to the disease. Further studies aimed at defining other MS
      susceptibility and disease-modifying genes are in progress.

PMID- 14600748
TI  - [Epilepsy and genetics].
AB  - The inheritance of epilepsy has been known since antiquity. Twin studies have
      shown that genes are important, particularly in primary generalised epilepsies,
      although the overall risk of epilepsy in offspring of parent with epilepsy is
      only approximately 6%. Many different protein structures control the normal
      activation of a brain neurone, and genes are responsible for the structure of
      these proteins. Mutations can lead to the characteristic pathological activation
      of epileptic neurones. Monogenic epilepsies may be related to changes in
      structures of importance for neuronal activation, e.g. the Na channel, the K
      channel, the GABA-A receptor, and in an acetylcholine receptor. A mutation has
      been demonstrated in a gene possibly related to brain development. Most likely,
      many primary epilepsies are polygenic. Epilepsy is also a part of many other
      genetic diseases. Susceptibility genes may be of importance for the development
      of certain epilepsies. De novo mutations may also occur. Studies in families with
      epilepsy may lead to the discovery of more monogenic epilepsies. Comparison
      between large populations of patients and controls is necessary in order to
      identify susceptibility genes in non-familiar epilepsy. The new knowledge of
      genetic aspects of epilepsy will bring improvements in diagnostics and treatment.

PMID- 14600749
TI  - [Intense debate on euthanasia within the European palliative care].

PMID- 14600750
TI  - [Drug treatment of newborn infants--a chance taking?].

PMID- 14600751
TI  - [The new biotechnology law and the old maternal age criterium].

PMID- 14600753
TI  - [Hospital autopsies--strong tradition under pressure].

PMID- 14600754
TI  - [Is information and communication technology harmful for the poor?].

PMID- 14600757
TI  - [Did anyone see a 100-year-old curriculum?].

PMID- 14600759
TI  - [Health minister's measures against tobacco injuries caused a war in the media].

PMID- 14600761
TI  - [Fetal valproate syndrome].

PMID- 14600762
TI  - [Be careful with sensations created by journals].

PMID- 14600764
TI  - [Physicians need knowledge of human rights, torture and conflicts].

PMID- 14600765
TI  - [Hospital politics on the wrong track?].

PMID- 14600768
TI  - Evaluation of fetal intrapartum hypoxia by middle cerebral and umbilical artery
      Doppler velocimetry with simultaneous cardiotocography and pulse oximetry.
AB  - OBJECTIVE: To investigate fetal circulation at different stages of hypoxia during
      labor, and to study blood flow alterations in the brain and peripheral tissues,
      through simultaneous use of three non-invasive techniques. MATERIALS AND METHODS:
      Ninety two pregnant women between 38 and 41 weeks of gestation, comparable for
      maternal age and parity, were simultaneously monitored with cardiotocography
      (CTG), continuous fetal pulse oximetry and Doppler ultrasonography during the
      first stage of labor. In 70 cases evaluation was successful, and useful data was
      obtained. Doppler waveforms were obtained before and during abnormal CTG
      patterns, of both the umbilical (UA) and middle cerebral artery (MCA) to measure
      the pulsatility index (PI), resistance index (RI), and flow velocity integral
      (FVI). The study population was divided in three groups, according to CTG and
      fetal pulse oximetry tracings: 20 term fetuses with normal CTG patterns and
      oxygen saturation (FSPO(2)) values >40%, 30 term fetuses with abnormal CTG
      patterns and FSPO(2) values between 30 and 40%, and 20 fetuses with abnormal CTG
      patterns and FSPO(2) values <30% for a time up to 2 min. These were studied and
      peripartum outcomes were compared. RESULTS: Redistribution of blood flow was
      noted at FSPO(2) values of 37%, in all groups. In the presence of reduced oxygen
      saturation (near to or below 30%), MCA Doppler showed significantly lower PI
      (1.06+/-0.33 vs.0.74+/-0.39, p=0.03) and RI (0.59+/-0.14 vs. 0.44+/-0.14,
      p=0.03), while that of the UA showed mildly higher resistance indices (0.98+/
      0.14 vs. 1.28+/-0.50, p=0.01 and 0.57+/-0.12 vs. 0.79+/-0.24, p=0.004,
      respectively). When an oxygen saturation value of <30% was maintained for greater
      than 2 min, MCA Doppler indices reversed, likely indicating morbid fetal hypoxia.
      Differences in fetal outcomes between groups correlated with Doppler and pulse
      oximetry tracings. CONCLUSIONS: During active labor the fetus maintains oxygen
      supply to the brain by redistributing blood flow. In cases of hypoxia this is
      feasible for only 2 min. We note a strong correlation between fetal pulse
      oximetry, Doppler velocimetry of the MCA and UA, and fetal morbidity.

PMID- 14600769
TI  - Return of the milk curd syndrome.
AB  - Five extremely low birth weight (ELBW) infants were treated in our institution
      for the milk curd syndrome, a milk bolus intestinal obstruction. The medical
      records of the five patients, who all underwent surgery, were retrospectively
      reviewed. History and examination are usually sufficient to diagnose the milk
      curd syndrome in ELBW infants. Confirmation with an abdominal X-ray may be
      possible but the X-ray findings may be mistaken for localised necrotising
      enterocolitis (NEC). Contrast enemas in an attempt to shift the bolus obstruction
      may be dangerous, and have a low success rate. Enterotomy and removal of the
      bolus is a safe and effective treatment if the diagnosis is early, otherwise
      resection with or without diverting ileostomy may be necessary. It appears that
      after years of disappearance, the milk curd syndrome has again become a clinical
      entity. It is probably due to a combination of high calcium and fat intake in an
      ever increasing population of ELBW infants.

PMID- 14600770
TI  - Life-threatening respiratory distress in a neonate with a pericardial cyst.
AB  - Our case report details the clinical course and management of a neonate with
      acute life-threatening respiratory distress presenting soon after birth. She
      needed intubation and ventilation. A pericardial cyst was diagnosed after a CT
      scan and 2D echo investigation. As a temporizing procedure the fluid was tapped
      and the child was electively operated. Postoperatively she made an uneventful and
      complete recovery. We have reviewed the literature for this rare and often
      asymptomatic lesion.

PMID- 14600771
TI  - Relapses in Wilms tumour.
AB  - During an 18-year period, 54 children were treated for Wilms tumour (WT).
      Thirteen of them, 6 boys and 7 girls, had a relapse. Mean age at diagnosis was 50
      months, range 5-233 months. The investigations revealed stage I in 5 cases, stage
      II in 2, stage III in 3, stage IV in 1 and stage V in 2.The histology was
      favourable in 6 cases, intermediate in 4 and unfavourable in 3. Clonal chromosome
      aberrations were detected in 8 cases. The mean time to first relapse was 17
      months, range 1-76 months. The location was the local region in 3 cases, other
      kidney in 3, lungs in 7 and skeletal in 2. A second relapse occurred in 6
      patients and a third relapse in 2 patients. Seven patients died after a mean
      follow-up of 84 months, range 42-180 months, from primary treatment. The 6
      surviving children had no evidence of disease after a mean follow-up of 70
      months, range 42-120 months, after treatment ended. High stage at diagnosis,
      unfavourable histologic subtype and occurrence of nephroblastomatosis were found
      not only in the children with relapse. No significant correlations were found
      when comparing the karyotypic features with clinical outcome. All 3 tumours with
      deletions of chromosome arm 16q metastasized.

PMID- 14600773
TI  - Interval-integration underlies amplitude modulation band-suppression selectivity
      in the anuran midbrain.
AB  - We examined the mechanisms that underlie 'band-suppression' amplitude modulation
      selectivity in the auditory midbrain of anurans. Band-suppression neurons respond
      well to low (5-10 Hz) and high (>70 Hz) rates of sinusoidal amplitude modulation,
      but poorly, if at all, to intermediate rates. The effectiveness of slow rates of
      sinusoidal amplitude modulation is due to the long duration of individual
      'pulses'; short-duration pulses (<10 ms) failed to elicit spikes when presented
      at 5-10 pulses s(-1). Each unit responded only after a threshold number of pulses
      (median=3, range=2-5) were delivered at an optimal rate. The salient stimulus
      feature was the number of consecutive interpulse intervals that were within a
      cell-specific tolerance. This interval-integrating process could be reset by a
      single long interval, even if preceded by a suprathreshold number of intervals.
      These findings indicate that band-suppression units are a subset of interval
      integrating neurons. Band-suppression neurons differed from band-pass interval
      integrating cells in having lower interval-number thresholds and broader interval
      tolerance. We suggest that these properties increase the probability of a
      postsynaptic spike, given a particular temporal pattern of afferent action
      potentials in response to long-duration pulses, i.e., predispose them to respond
      to slow rates of amplitude modulation. Modeling evidence is provided that
      supports this conclusion.

PMID- 14600772
TI  - Oral tumors and tumor-like lesions in infants and children.
AB  - The aim of this retrospective study was to survey the spectrum of oral tumors and
      tumor-like lesions treated in a pediatric surgical unit. The clinical features
      and treatment outcome are presented, and guidelines for management discussed.
      Long-term follow-up was carried out both by re-examination and by means of a
      questionnaire. A total of 95 patients were encountered over a 30-year period. The
      age at presentation ranged from 1 day to 16 years, and the male to female ratio
      was 0.7:1. The lesions were located predominantly on the lips (22%), tongue
      (21%), and cheek (19%). Patients were divided into five groups based on
      histological diagnosis. Benign lesions accounted for 83 (87%) of the cases. Of
      these, 41 (43%) were benign tumors, the most common of which were the hemangiomas
      (17 cases). Hamartomas accounted for a further 22 benign lesions (23%), among
      which 12 were lymphangiomas. Furthermore, we saw 14 cases (15%) of mucoceles,
      ranula and dysontogenetic cysts, and a further 6 cases (6%) were classed as
      miscellaneous lesions. Simple surgical resection was successful in treating most
      benign lesions, with occasional re-excision being necessary in lymphangiomas. The
      long-term effects of treatment include reduction of the red volume of the lips,
      scarring following resection of parotid hemangiomas, a forked tongue after wedged
      resection, and partial facial nerve palsy. The group of 12 (13%) malignant tumors
      consisted of 5 rhabdomyosarcomas, 2 fibrosarcomas, 2 carcinomas of the parotid, 1
      osteosarcoma, and 2 metastases. A multimodal approach was used in patients with
      rhabdomyosarcomas, while fibrosarcomas and parotid carcinomas were normally
      treated by surgical excision. Six of 12 patients with malignant tumors were alive
      after a median follow-up of 20.5 years. Re-examination of the malignant tumor
      group revealed scarring, impaired growth and function of the maxilla associated
      with local irradiation, and an external salivary fistula. In conclusion, while
      most oral and maxillofacial tumors of children are benign, malignant tumors of
      soft tissue, salivary glands and bones must be taken into account. There are
      specific aspects related to certain developmental and biological characteristics
      that make a mainly conservative approach preferable in these children.

PMID- 14600774
TI  - T2 relaxation time analysis in patients with multiple sclerosis: correlation with
      magnetization transfer ratio.
AB  - The aim of the current study was to perform T2 relaxation time measurements in
      multiple sclerosis (MS) patients and correlate them with magnetization transfer
      ratio (MTR) measurements, in order to investigate in more detail the various
      histopathological changes that occur in lesions and normal-appearing white matter
      (NAWM). A total number of 291 measurements of MTR and T2 relaxation times were
      performed in 13 MS patients and 10 age-matched healthy volunteers. Measurements
      concerned MS plaques (105), NAWM (80), and "dirty" white matter (DWM; 30), evenly
      divided between the MS patients, and normal white matter (NWM; 76) in the healthy
      volunteers. Biexponential T2 relaxation-time analysis was performed, and also
      possible linearity between MTR and mean T2 relaxation times was evaluated using
      linear regression analysis in all subgroups. Biexponential relaxation was more
      pronounced in "black-hole" lesions (16.6%) and homogeneous enhancing plaques
      (10%), whereas DWM, NAWM, and mildly hypointense lesions presented biexponential
      behavior with a lower frequency(6.6, 5, and 3.1%, respectively). Non-enhancing
      isointense lesions and normal white matter did not reveal any biexponential
      behavior. Linear regression analysis between monoexponential T2 relaxation time
      and MTR measurements demonstrated excellent correlation for DWM( r=-0.78,
      p<0.0001), very good correlation for black-hole lesions( r=-0.71, p=0.002), good
      correlation for isointense lesions( r=-0.60, p=0.005), moderate correlation for
      mildly hypointense lesions( r=-0.34, p=0.007), and non-significant correlation
      for homogeneous enhancing plaques, NAWM, and NWM. Biexponential T2 relaxation
      time behavior is seen in only very few lesions (mainly on plaques with high
      degree of demyelination and axonal loss). A strong correlation between MTR and
      monoexponential T2 values was found in regions where either inflammation or
      demyelination predominates; however, when both pathological conditions coexist,
      this linear relationship is lost.

PMID- 14600775
TI  - Diagnosis of acute fractures of the extremities: comparison of low-field MRI and
      conventional radiography.
AB  - The aim of this study was to compare low-field MRI (0.2 T) and conventional
      radiography for the detection of acute fractures of the distal part of the
      extremities. X-ray and MRI examinations of 78 (41 fractures, 37 without fracture)
      patients with the clinical suspicion of an acute fracture in the distal part of
      the extremities were compared. Four experienced radiologists, two for each of the
      two modalities, independently analyzed the images. Interobserver variability and
      receiver operating characteristic (ROC) analysis for both methods were
      established. The MRI and conventional radiography revealed an accuracy of 81.4
      and of 79.5%, respectively, in the detection of acute fractures. The diagnostic
      accuracy of MRI to detect fractures in the hand and forefoot proved to be
      significantly inferior to conventional X-ray examinations. On the other hand, MRI
      achieved a better accuracy for the examination of bones near a large joint. The
      interobserver variability for both methods was rated as moderate. In ROC analysis
      both methods were rated as good. There was no statistical difference of the
      accuracy between low-field MRI and conventional radiography in the detection of
      acute fractures of the distal part of the extremities. Consequently, a routine
      use of low-field MRI as an alternative to conventional radiography to diagnose
      acute fractures of the extremities seems not to be justified.

PMID- 14600776
TI  - Potential clinical relevance of digital radiogrammetry for quantification of
      periarticular bone demineralization in patients suffering from rheumatoid
      arthritis depending on severity and compared with DXA.
AB  - The aim of this study was to investigate a new bone densitometric technology
      based on digital radiogrammetry (DXR) with respect to its ability to measure
      severity-dependent variations of bone mineralization in patients with rheumatoid
      arthritis. One hundred six randomly selected patients suffering from verified
      rheumatoid arthritis underwent digitally performed plain radiographs of the non
      dominant hand and measurements of dual-energy X-ray absorptiometry (DXA)
      regarding total femur and lumbar spine. Using DXR the radiographs were analyzed
      retrospectively for bone mineral density (BMD) calculation. The severity was
      classified using Larsen score and Steinbroker stage blinded by two radiologists.
      A third radiologist reviewed the incongruently scored cases. Mean values of
      calculated parameters changed as follows from Larsen 1 to Larsen 5: Bone mineral
      density (DXR-BMD) decreased from 0.55 to 0.44 g/cm2 (p=0.000), DXR-MCI decreased
      from 0.44 to 0.33 (p=0.001), DXA-BMD (total femur) decreased from 0.92 to 0.78
      g/cm2 (p=0.090) and DXA-BMD (lumbar spine) decreased from 0.91 to 0.84 g/cm2
      (p=0.595). Similar results were verified for the Steinbroker stage. The relative
      decrease of BMD measured by DXR between the highest and lowest score was 20% for
      Steinbroker stage and Larsen score (p<0.05). The relative decrease of BMD using
      DXA revealed not such a significant result. Similar results were verified for
      metacarpal index (estimated by DXR). Correlations between BMD determined by DXR
      and by DXA were all significant (R=0.45 for lumbar spine and R=0.59 for total
      femur). Consequently, less than 35% of the DXR-BMD value is explainable by
      corresponding DXA values. The DXR-based BMD calculation seems to be able to
      distinguish severity and progress of the disease in contrast to those of DXA at
      lumbar spine and total femur.

PMID- 14600777
TI  - Flow ghost artifact in slice-encoding direction mimicking vestibular schwannoma
      in contrast-enhanced 3D spoiled gradient-echo sequence.
AB  - The value of MR imaging by post-contrast T1-weighted 3D spoiled gradient-echo (3D
      SPGR) is well established for the detection of small vestibular schwannomas in
      the cerebellopontine angle region. We describe a case in which a flow ghost
      artifact in the slice-encoding direction mimicked a vestibular schwannoma and
      heavily T2-weighted MR cisternography and multiplanar reconstruction images
      helped us to reach the correct diagnosis. In addition, we conducted a volunteer
      study to demonstrate that changing the k-space trajectory can reduce this
      artifact in post-contrast 3D SPGR images.

PMID- 14600778
TI  - Gadobenate dimeglumine-enhanced liver MR imaging: value of dynamic and delayed
      imaging for the characterization and detection of focal liver lesions.
AB  - The aim of this study was to determine the value of delayed-phase imaging (DPI)
      of gadobenate dimeglumine (Gd-BOPTA)-enhanced MR imaging for the evaluation of
      focal hepatic tumors compared with precontrast imaging and early dynamic phase
      imaging. The MR images were obtained in 48 patients with 98 focal hepatic tumors.
      Three-dimensional gradient-echo (GRE) imaging obtained before and 30, 60, and 1 h
      after administration of 0.1 mmol/kg of gadobenate dimeglumine. Each image set was
      analyzed qualitatively (lesion detection, conspicuity, delineation, and
      enhancement pattern on DPI) and quantitatively [signal-to-noise ratio (SNR),
      tumor-liver contrast-to-noise ratio (CNR)]. Improved lesion-to-liver contrast
      during the dynamic phase imaging was observed compared with precontrast images.
      The DPI showed a homogeneous enhancement of liver parenchyma and distinctive
      enhancement features of focal liver lesions: metastases (85%) showed a target
      shaped enhancement, and hepatocellular carcinomas (HCCs) showed an inhomogeneous
      (58%) or homogeneous enhancement (21%). The DPI showed better performance for the
      detection of metastases than other images by increasing lesion delineation (
      p<0.05). The absolute CNR of metastasis measured from periphery of the tumors on
      DPI was greater than precontrast and arterial phase imaging ( p<0.05). The Gd
      BOPTA during both dynamic and delayed phases provides valuable information for
      the characterization of focal liver lesions, and furthermore, Gd-BOPTA-enhanced
      DPI contributed to the improved detection of liver metastasis compared to
      precontrast and early dynamic imaging.

PMID- 14600779
TI  - Ultrastructural MR imaging techniques of the knee articular cartilage: problems
      for routine clinical application.
AB  - The high incidence of cartilage lesions together with new surgical treatment
      techniques have necessitated the development of noninvasive cartilage evaluation
      techniques. Although arthroscopy has been the standard for cartilage evaluation,
      MR imaging has emerged as the imaging method of choice, allowing morphological
      evaluation of cartilage and cartilage repair tissue, as well as evaluation of its
      biochemical content. This article deals with current ultrastructural MR imaging
      techniques for cartilage evaluation, indicating the advantages as well as the
      drawbacks for routine clinical application.

PMID- 14600780
TI  - Pre-surgical mapping of primary motor cortex by functional MRI at 3 T: effects of
      intravenous administration of Gd-DTPA.
AB  - The functional magnetic resonance imaging (fMRI) is often performed at the end of
      a routine MRI examination during which, dependent on the clinical indication,
      contrast agent has been administered; however, the effects of Gd-DTPA injection
      on the results of blood oxygenation level dependent (BOLD)-fMRI remain unknown.
      The present study was conducted to investigate the effects of the intravenous
      administration of Gd-DTPA on the results of pre-surgical localization of the
      primary motor cortex by BOLD-fMRI at 3 T. Eight normal subjects were included in
      this study. After the anatomical scans, pre- and post-contrast fMRI scanning was
      performed. The number of significantly activated voxels and the mean percentage
      signal change were compared. The mean number of significantly activated voxels
      was 115.0+/-27.0 in pre-contrast runs and 90.8+/-27.1 in post-contrast runs (mean
      value of all 8 volunteers+/-standard deviation; p<0.05). The mean mean percentage
      signal change was 4.07+/-0.39 in pre-contrast runs and 3.86+/-1.91 in post
      contrast runs ( p=0.16). Pre-surgical localization of the motor area by BOLD-fMRI
      should be performed before the administration of Gd contrast material.

PMID- 14600781
TI  - Callus induction and regeneration in Spirodela and Lemna.
AB  - The development of tissue culture systems in duckweeds has, to date, been limited
      to species of the genus Lemna. We report here the establishment of an efficient
      tissue culture cycle (callus induction, callus growth and plant regeneration) for
      Spirodela oligorrhiza Hegelm SP, Spirodela punctata 8717 and Lemna gibba var.
      Hurfeish. Significant differences were found among the three duckweed species
      pertaining to carbohydrate and phytohormone requirements for callus induction,
      callus growth and frond regeneration. In vitro incubation with poorly assimilated
      carbohydrates such as galactose ( S. oligorrhiza SP and L. gibba var. Hurfeish)
      and sorbitol ( S. punctata 8717) as sole carbon source yielded high levels of
      callus induction on phytohormone-supplemented medium. Sorbitol is required for
      optimal callus growth of S. oligorrhiza SP and S. punctata 8717, while sucrose is
      required for callus growth of L. gibba var. Hurfeish. Sucrose either alone ( S.
      oligorrhiza SP, L. gibba var. Hurfeish) or in addition to sorbitol ( S. punctata
      8717) is required for frond regeneration.

PMID- 14600782
TI  - Interactions of phytochromes A, B1 and B2 in light-induced competence for
      adventitious shoot formation in hypocotyl of tomato (Solanum lycopersicum L.).
AB  - The interactions of phytochrome A (phyA), phytochrome B1 (phyB1) and phytochrome
      B2 (phyB2) in light-dependent shoot regeneration from the hypocotyl of tomato was
      analysed using all eight possible homozygous allelic combinations of the null
      mutants. The donor plants were pre-grown either in the dark or under red or far
      red light for 8 days after sowing; thereafter hypocotyl segments (apical, middle
      and basal portions) were transferred onto hormone-free medium for culture under
      different light qualities. Etiolated apical segments cultured in vitro under
      white light showed a very high frequency of regeneration for all of the genotypes
      tested besides phyB1phyB2, phyAphyB1 and phyAphyB1phyB2 mutants. Evidence is
      provided of a specific interference of phyB2 with phyA-mediated HIR to far-red
      and blue light in etiolated explants. Pre-treatment of donor plants by growth
      under red light enhanced the competence of phyB1phyB2, phyAphyB1 and
      phyAphyB1phyB2 mutants for shoot regeneration, whereas pre-irradiation with far
      red light enhanced the frequency of regeneration only in the phyAphyB1 mutant.
      Multiple phytochromes are involved in red light- and far-red light-dependent
      acquisition of competence for shoot regeneration. The position of the segments
      along the hypocotyl influenced the role of the various phytochromes and the
      interactions between them. The culture of competent hypocotyl segments under red,
      far-red or blue light reduced the frequency of explants forming shoots compared
      to those cultured under white light, with different genotypes having different
      response patterns.

PMID- 14600783
TI  - Epidermoid cyst mimicking monoarticular arthritis of the great toe.
AB  - Local swellings of the foot are a common presentation in rheumatological
      practice. In the following case report, an epidermoid cyst presenting with the
      typical features of monoarticular arthritis is described in a 27-year-old woman.
      The differential diagnosis of forefoot swelling is discussed, with particular
      emphasis on epidermoid cysts and monoarticular arthritis.

PMID- 14600784
TI  - Collagen turnover is diminished by different clones of skin fibroblasts from
      early- but not late-stage systemic sclerosis.
AB  - To investigate collagen turnover and proliferation in dermal fibroblasts from
      patients with systemic sclerosis (SSc) and their relationship with disease
      duration and cellular subpopulations, SSc patients were grouped by disease
      duration (less than 2.5 years or more than 7 years). Control and SSc fibroblasts
      were obtained from skin biopsies. Collagen biosynthesis was determined by [14C]
      proline uptake. Type I/III collagens, gelatinolytic activity, and tissue
      inhibitors of metalloproteinases (TIMP)-1 and -2 were evaluated by
      electrophoresis, zymography, and enzyme-linked immunosorbent assay, respectively.
      Total collagen synthesis and the levels of alpha1(I), alpha2(I), and alpha1(III)
      chains, as well as TIMP-1 and proliferation were increased in fibroblasts only
      from patients with early-stage SSc. Gelatinolytic activity did not vary among the
      groups. This metabolic condition favors a higher local fibroblast population and
      is characterized by a heterogeneous clonal response in which the majority
      exhibited higher levels of collagen and TIMP-1 synthesis as well as an increase
      in their proliferation patterns involving hyper-reactive fibroblast subsets.

PMID- 14600785
TI  - Color-coded sonography in suspected temporal arteritis-experiences after 83
      cases.
AB  - Color-coded sonography is an interesting option for the diagnosis of temporal
      arteritis. We present our experiences regarding examination technique and
      diagnostic accuracy, comparing biopsy and clinical results in a series of 83
      patients with suspected temporal arteritis. A dark halo around the vessel wall
      (representing inflammatory oedema), reduced or absent vessel wall pulsations
      (demonstrated by M mode), and vessel occlusions were used as diagnostic criteria.
      Forty-eight patients underwent biopsy of the temporal artery following ultrasound
      examination. Comparing these findings with biopsy yielded a sensitivity of 73%,
      specificity of 93%, positive predictive value (PPV) of 96%, and negative
      predictive value (NPV) of 58%. The halo sign alone had a lower sensitivity (67%).
      Comparison with overall clinical assessment (n = 83) yielded a sensitivity of
      65%, specificity of 100%, PPV of 100%, and NPV of 73%. Irregular atherosclerotic
      vessel wall changes were the main differential diagnosis. Important pitfalls were
      false focus setting, too much/less color gain, and 'bifurcation halo'. In
      conclusion, a positive sonographic result in combination with typical clinical
      signs might replace the need for biopsy, while a negative result should not be
      used for exclusion of temporal arteritis. Considering the low PPV and high NPV of
      the clinical criteria defined by the American College of Rheumatology, color
      coded sonography is a useful tool in the noninvasive diagnostic workup of
      temporal arteritis.

PMID- 14600786
TI  - Decreased serum level of antibody against human cytomegalovirus in patients with
      Behcet's disease.
AB  - Behcet's disease (BD) is a connective tissue disorder characterized by recurrent
      orogenital ulcer, uveitis, and skin lesions. Recurrent aphthous ulcer is
      associated with human cytomegalovirus (HCMV). To investigate the possible role of
      HCMV in BD, we measured the titers of IgG, IgM, and IgA anti-HCMV antibodies in
      73 Korean patients with BD, 50 with scleroderma, 70 with systemic lupus
      erythematosus, and 50 from healthy controls by indirect immunofluorescent
      staining. The titer of IgG anti-HCMV antibody was significantly lower in patients
      with BD than in controls (geometric mean 3115.4 vs 9687.6, P = 0.0001 by
      Wilcoxon's rank sum test), as was the titer of IgA anti-HCMV antibody (geometric
      mean 1.9 vs 15.7, P = 0.0001, Wilcoxon's rank sum test). In conclusion, we found
      significantly lower antibody responses to HCMV in patients with BD.

PMID- 14600787
TI  - Cytokine inhibitors: soluble tumor necrosis factor receptor 1 and interleukin-1
      receptor antagonist in Behcet's disease.
AB  - Serum levels of proinflammatory cytokines, interleukin-1 beta (IL-1beta), tumor
      necrosis factor alpha, (TNF-alpha), and their inhibitors, IL-1 receptor
      antagonist (IL-1ra) and soluble TNF receptor 1 (sTNFR1), were determined by
      enzyme-linked immunosorbent assay in 104 patients with Behcet's disease (65
      active, 39 inactive) and 40 healthy controls. The levels of IL-1beta and IL-1ra
      were significantly higher in both active and inactive patients than in control
      subjects (P<0.01 and P< 0.01, respectively). The concentrations of TNF-alpha and
      sTNFR1 were found to be higher in active patients than in controls (P< 0.01 and
      P< 0.001, respectively). There were no significant differences in the serum
      levels of these cytokines and their inhibitors between active and inactive
      patients. Significant increases in mean C-reactive protein level and erythrocyte
      sedimentation rate were found in patients with active vs inactive disease (P<
      0.001 and P< 0.05, respectively). C-reactive protein values correlated with
      erythrocyte sedimentation rate but not with cytokines or their inhibitors. Our
      conclusion is that elevated serum TNF-alpha and sTNFR1 seem to be important
      inflammatory mediators in Behcet's disease. The statistically significant
      increase in these levels may arise from the severity of inflammation in the
      tissue or organ involved.

PMID- 14600788
TI  - The laccase gene family in Coprinopsis cinerea (Coprinus cinereus).
AB  - In this study, we isolated and sequenced eight non-allelic laccase genes from
      Coprinopsis cinerea ( Coprinus cinereus) homokaryon AmutBmut. These eight genes
      represent the largest laccase gene family identified so far in a single haploid
      fungal genome. We analyzed the phylogenetic relationships between these genes by
      intron positions, amino acid sequence conservation and similarities in promoter
      sequences. All deduced protein products have the laccase signature sequences L1
      L4, the typical conserved cysteine and the ten histidine residues which are
      ligands in the two laccase copper-binding centers, T1 and T2/T3. Proteins Lcc2
      and Lcc3 of Coprinopsis cinerea are most similar to the acidic, membrane
      associated laccase CLAC2 from Coprinellus congregatus implicated in
      neutralization of acidic medium. All other laccases from the saprophyte
      Coprinopsis cinerea, including the well described enzyme Lcc1, form a cluster
      separate from these three enzymes and from various laccases of wood-rotting and
      plant-pathogenic basidiomycetes.

PMID- 14600789
TI  - Radiological evidence of anatomical variation of the inferior vena cava: report
      of two cases.
AB  - The inferior vena cava (IVC) is a retroperitoneal key structure whose location
      and integrity must be checked in every scan. A number of studies are reported in
      the literature concerning congenital variations of the inferior vena cava.
      Anatomical variations of this main venous trunk are relatively infrequent
      clinical findings during surgery or diagnostic procedures in patients without
      symptoms such as an aberrant venous drainage or abdominal pain. Among the other
      imaging techniques, computerized tomography is a non-invasive, effective
      technique for diagnosing diseases of the retroperitoneal space and, particularly,
      for detecting anomalies of the main vessels, such as the aorta or IVC, in
      asymptomatic patients. We present two cases of IVC variation as an incidental
      finding in patients studied by means of CT scan for the gradation of kidney
      carcinoma and pancreatic cancer respectively. Two different configurations of the
      system of the IVC (agenesis of the IVC with hypertrophy of the azygos vein and a
      double IVC respectively) were found in our cases. The embryological development
      of the IVC system is discussed, bearing in mind that knowledge of the different
      variations is important in order to avoid major surgical complications.

PMID- 14600790
TI  - Phase I/II study of treatment with dendritic cell vaccines in patients with
      disseminated melanoma.
AB  - Previous studies have suggested that immunotherapy with dendritic cell (DC)
      vaccines may be effective in treatment of patients with AJCC stage IV melanoma.
      We examined this treatment in phase I/II studies in 33 patients with good
      performance status and low volume disease. Nineteen patients received DCs plus
      autologous lysates and 14 patients DCs plus peptides from the melanoma antigens
      MAGE-3.A2, tyrosinase, gp100, and MART-1. Keyhole limpet hemocyanin (KLH) was
      used as a helper protein and influenza peptide was given as a positive control.
      DCs were produced from adherent cells in blood lymphocytes (monocytic DCs), grown
      in IL-4 and GM-CSF without a maturation step. The DCs were injected into inguinal
      lymph nodes at weekly intervals (x4), 2 weeks (x1), and 4-weekly intervals (x2).
      There were 3 responses (3 partial responses) and 1 mixed response in the 19
      patients treated with DCs plus autologous lysates. No responses were seen in the
      group treated with DCs plus peptides. Stable disease (defined as no progression
      over a period of 3 months) was seen in 4 patients in group 1 and 5 patients in
      group 2. Treatment was not associated with significant side effects. We examined
      whether DTH skin tests or assays of IFN-gamma cytokine production may be useful
      predictors of clinical responses. Twenty-two of 30 patients had DTH responses to
      KLH and 12 of 13 patients had DTH responses to the influenza peptide. Five of 15
      DTH responses were seen against autologous lysates. This was strongly correlated
      with clinical responses. Approximately half the patients had responses to MART-1
      peptide and a third to the other melanoma peptides. Similarly, cytokine
      production assays showed responses to influenza in 7 of 13 patients, and
      approximately one third of patients had responses to the other peptides. No IFN
      gamma responses were seen in 5 patients against their autologous lysates. There
      was no correlation between assays of IFN-gamma production and clinical responses.
      The present studies suggest that autologous lysates may be more effective than
      the melanoma peptides used in the study as the source of antigen for DC vaccines.
      DTH responses to autologous lysates appear useful predictors of clinical
      responses, but further work is needed to identify other measures associated with
      clinical responses.

PMID- 14600791
TI  - Purification and characterization of arylsulfatase from Sphingomonas sp. AS6330.
AB  - Arylsulfatase was purified from Sphingomonas sp. AS6330 through ionic exchange,
      hydrophobic- and gel-chromatographies. The purity increased 12,800-fold with
      approximately 19.1% yield against cell homogenate. The enzyme was a monomeric
      protein with apparent molecular weight of 62 kDa as determined by sodium
      dodecylsulfate-polyacrylamide gel electrophoresis, and 41 kDa as determined by
      gel filtration. The enzyme had optimum reaction conditions for hydrolysis of
      sulfate ester bonds in agar and p-nitrophenyl sulfate (NPS) at pH 7.0 and 45
      degrees C, with a specific activity of 3.93 and 97.2 U, respectively. The enzyme
      showed higher activity towards agar than other sulfated marine polysaccharides
      such as porphyran, fucoidan and carrageenan. The K(m) and V(max) of the enzyme
      for hydrolysis of NPS were 54.9 microM and 113 mM/min, respectively. With
      reaction of 200 g agar with 100 U arylsulfatase for 8 h at 45 degrees C, gel
      strength increased 2.44-fold, and 97.7% of the sulfate in the agar was
      hydrolyzed.

PMID- 14600792
TI  - Metabolite profiles of the biocontrol yeast Pichia anomala J121 grown under
      oxygen limitation.
AB  - The biocontrol yeast Pichia anomala J121 prevents mould growth during the storage
      of moist grain under low oxygen/high carbon dioxide conditions. Growth and
      metabolite formation of P. anomala was analyzed under two conditions of oxygen
      limitation: (a) initial aerobic conditions with restricted oxygen access during
      the growth period and (b) initial microaerobic conditions followed by
      anaerobiosis. Major intra- and extracellular metabolites were analyzed by high
      resolution magic-angle spinning (HR-MAS) NMR and HPLC, respectively. HR-MAS NMR
      allows the analysis of major soluble compounds inside intact cells, without the
      need for an extraction step. Biomass production was higher in treatment (A),
      whereas the specific ethanol production rate during growth on glucose was similar
      in both treatments. This implies that oxygen availability affected the
      respiration and not the fermentation of the yeast. Following glucose depletion,
      ethanol was oxidized to acetate in treatment (A), but continued to be produced in
      (B). Arabitol accumulated in the culture substrate of both treatments, whereas
      glycerol only accumulated in treatment (B). Trehalose, arabitol, and glycerol
      accumulated inside the cells in both treatments. The levels of these metabolites
      were generally significantly higher in treatment (B) than in (A), indicating
      their importance for P. anomala during severe oxygen limitation/anaerobic
      conditions.

PMID- 14600793
TI  - Natural and recombinant fungal laccases for paper pulp bleaching.
AB  - Three laccases, a natural form and two recombinant forms obtained from two
      different expression hosts, were characterized and compared for paper pulp
      bleaching. Laccase from Pycnoporus cinnabarinus, a well known lignolytic fungus,
      was selected as a reference for this study. The corresponding recombinant
      laccases were produced in Aspergillus oryzae and A. niger hosts using the lacI
      gene from P. cinnabarinus to develop a production process without using the
      expensive laccase inducers required by the native source. In flasks, production
      of recombinant enzymes by Aspergilli strains gave yields close to 80 mg l(-1).
      Each protein was purified to homogeneity and characterized, demonstrating that
      the three hosts produced proteins with similar physico-chemical properties,
      including electron paramagnetic resonance spectra and N-terminal sequences.
      However, the recombinant laccases have higher Michaelian (Km) constants,
      suggesting a decrease in substrate/enzyme affinity in comparison with the natural
      enzyme. Moreover, the natural laccase exhibited a higher redox potential (around
      810 mV), compared with A. niger (760 mV) and A. oryzae (735 mV). Treatment of
      wheat straw Kraft pulp using laccases expressed in P. cinnabarinus or A. niger
      with 1-hydroxybenzotriazole as redox mediator achieved a delignification close to
      75%, whereas the recombinant laccase from A. oryzae was not able to delignify
      pulp. These results were confirmed by thioacidolysis. Kinetic and redox potential
      data and pulp bleaching results were consistent, suggesting that the three
      enzymes are different and each fungal strain introduces differences during
      protein processing (folding and/or glycosylation).

PMID- 14600794
TI  - Hypertrophic osteoarthropathy in primary liver rhabdomyosarcoma.
AB  - Hypertrophic osteoarthropathy is a well-documented paraneoplastic phenomenon in
      adults. It is a rare, but important finding in children with malignant disease as
      it can indicate prognosis. We present a case of hypertrophic osteoarthropathy
      associated with primary liver rhabdomyosarcoma in a 14-year-old boy.

PMID- 14600795
TI  - Non-Hodgkin's lymphoma presenting with uterine and renal enlargement in a young
      girl.
AB  - Non-Hodgkin's lymphoma (NHL) is the fourth most common childhood malignancy.
      Uterine involvement with NHL is well described in adults, rare in children and
      has not been described in the first 2 years of life. While renal involvement in
      NHL is well recognised, diffuse renal enlargement is an uncommon finding. We
      report a unique case of B-cell lymphoma of primitive phenotype in a 15-month-old
      girl with uterine and renal involvement at presentation. We describe the US and
      MRI features at presentation that helped in the prospective diagnosis of this
      condition.

PMID- 14600796
TI  - Visuo-vestibular interaction in the reconstruction of travelled trajectories.
AB  - We recently published a study of the reconstruction of passively travelled
      trajectories from optic flow. Perception was prone to illusions in a number of
      conditions, and was not always veridical in the others. Part of the illusionary
      reconstructed trajectories could be explained by assuming that subjects base
      their reconstruction on the ego-motion percept built during the stimulus' initial
      moments. In the current paper, we test this hypothesis using a novel paradigm: if
      the final reconstruction is governed by the initial percept, providing
      additional, extra-retinal information that modifies the initial percept should
      predictably alter the final reconstruction. The extra-retinal stimulus was tuned
      to supplement the information that was under-represented or ambiguous in the
      optic flow; the subjects were physically displaced or rotated at the onset of the
      visual stimulus. A highly asymmetric velocity profile (high acceleration, very
      low deceleration) was used. Subjects were required to guide an input device (in
      the form of a model vehicle; we measured position and orientation) along the
      perceived trajectory. We show for the first time that a vestibular stimulus of
      short duration can influence the perception of a much longer-lasting visual
      stimulus. Perception of the ego-motion translation component in the visual
      stimulus was improved by a linear physical displacement, perception of the ego
      motion rotation component by a physical rotation. This led to a more veridical
      reconstruction in some conditions, but to a less veridical reconstruction in
      other conditions.

PMID- 14600797
TI  - Central auditory processing: integration with other systems. Proceedings of a
      meeting, May 2002 in Ascona, Switzerland.

PMID- 14600798
TI  - CNS somatosensory-auditory interactions elicit or modulate tinnitus.
AB  - Evidence has accumulated linking clinical tinnitus to the somatosensory system.
      Most clinical tinnitus patients can change the psychoacoustic attributes of their
      tinnitus with forceful head and neck contractions. The significance of such
      somatic modulation of tinnitus was assessed by testing non-clinical subjects.
      Like clinical tinnitus patients, about 80% of non-clinical subjects who had
      ongoing tinnitus at the time of testing (whether or not they had been previously
      aware of it) could modulate their tinnitus with head and neck contractions.
      Almost 60% of those with no tinnitus at the time of testing could elicit a
      tinnitus-like auditory percept with head and neck contractions. Because similar
      results were found in the profoundly deaf, we conclude that somatosensory
      auditory interactions within the central nervous system account for most, if not
      all, somatic modulation of tinnitus as well as the development of auditory
      percepts with somatic testing. Other observations implicate the muscle spindle as
      initiating the neural activation that ultimately modulates the central auditory
      pathway, including the dorsal cochlear nucleus. Somatic influences upon auditory
      perception are not limited to tinnitus subjects but are a fundamental property of
      the auditory system.

PMID- 14600799
TI  - LC-APCI-MS-MS methodology for determination of glybenclamide in human plasma.
AB  - A liquid chromatographic/atmospheric pressure chemical ionization tandem mass
      spectrometric method (LC-APCI-MS-MS) for the determination of glybenclamide in
      human plasma is described. Glypizide, an analogue of glybenclamide, was used as
      internal standard. The analyte was extracted from plasma with diethyl
      ether/dichloromethane (70:30 v/v). The chromatography uses C18 and 0.01 mol L(-1)
      acetic acid/acetonitrile (20:80 v/v) as stationary and mobile phase,
      respectively. Quantitation was preformed by using multiple reaction monitoring
      (MRM) of the precursor ion (m/z 494.2-->368.8) and the related product ion (m/z
      446.0-->347.3) using the internal standard method. The analytical curve was
      linear in the range 1-300 ng mL(-1), and for a 400-microL sample of human plasma,
      the limit of determination of the method was 1 ng mL(-1). The coefficients of
      variation of the method for intra-assay (within-run precision) and inter-assay
      (between-run precision) were less than 10%. The method was shown to be suitable
      for pharmacokinetic studies.

PMID- 14600800
TI  - Susceptibility to amphetamine-induced place preference is predicted by locomotor
      response to novelty and amphetamine in the mouse.
AB  - RATIONALE: It has been demonstrated that major differences between mice of the
      C57BL/6J and DBA/2J inbred strains for amphetamine-induced place conditioning
      (preference and avoidance, respectively) are evident in standard housing
      conditions but abolished by temporary restricted feeding. This gene-experience
      model may be usefully exploited to dissect behavioral phenotypes related to place
      conditioning induced by addictive drugs. OBJECTIVES: This study evaluated a
      number of behavioral phenotypes related to amphetamine-induced place preference
      for strain differences (C57BL/6J vs DBA/2J) susceptible to be abolished by
      temporary food restriction. METHODS: Mice of the two inbred strains were tested
      for: (1) conditioned taste aversion and place preference induced by amphetamine
      within the same dose-range; (2) preference for a novel compartment 24 h after a
      single exposure to only one of two compartments; (3) amphetamine-induced
      behavioral sensitization and conditioned hyperactivity; and (4) locomotor
      activity during exploration of a novel environment. RESULTS: The two strains
      showed consistent taste aversion at doses of amphetamine that promoted opposite
      strain-dependent place conditioning. Both strains spent more time exploring the
      novel rather than the known compartment of the place conditioning apparatus.
      Instead, only mice of the C57 strain showed amphetamine-induced behavioral
      sensitization and conditioned hyperactivity. However, temporary food restriction
      did not affect strain differences for these phenotypes. Finally, C57 mice were
      more active than DBA in a novel environment and restricted feeding abolished this
      strain-dependent difference. CONCLUSIONS: These results relate individual
      differences for amphetamine-induced place conditioning with locomotor response to
      amphetamine and novelty.

PMID- 14600801
TI  - AMPA-receptor activation is involved in the antiamnesic effect of DM 232
      (unifiram) and DM 235 (sunifiram).
AB  - DM 232 and DM 235 are novel antiamnesic compounds structurally related to
      ampakines. The involvement of AMPA receptors in the mechanism of action of DM 232
      and DM 235 was, therefore, investigated in vivo and in vitro. Both compounds (0.1
      mg/kg(-1) i.p.) were able to reverse the amnesia induced by the AMPA receptor
      antagonist NBQX (30 mg/kg(-1) i.p.) in the mouse passive avoidance test. At the
      effective doses, the investigated compounds did not impair motor coordination, as
      revealed by the rota rod test, nor modify spontaneous motility and inspection
      activity, as revealed by the hole board test. DM 232 and DM 235 reversed the
      antagonism induced by kynurenic acid of the NMDA-mediated release of [(3)H]NA in
      the kynurenate test performed in rat hippocampal slices. This effect was
      abolished by NBQX. DM 232 increases, in a concentration dependent manner,
      excitatory synaptic transmission in the rat hippocampus in vitro. These results
      suggest that DM 232 and DM 235 act as cognition enhancers through the activation
      of the AMPA-mediated neurotransmission system.

PMID- 14600803
TI  - Age-related changes in the protein and mRNA levels of CYP2E1 and CYP3A isoforms
      as well as in their hepatic activities in Wistar rats. What role for oxidative
      stress?
AB  - Drug biotransformation and its therapeutic effect may be modified during ageing.
      Among different causative factors of ageing, the impairment of normal cellular
      functions by free radicals has been evoked as playing a critical role. The effect
      of age on the expression and activity of CYP2E1 and CYP3A was investigated in
      male Wistar rats of 3, 8, 11 and 18 months old. The total cytochrome P450 as well
      as the expression and the activity (midazolam oxidation) of CYP3A isoforms did
      not change until 18 months of age. Chlorzoxazone hydroxylation (CYP2E1 activity)
      increased from 3 to 8 months, remained constant between 8 and 11 months and then
      progressively decreased until 18 months. Interestingly, CYP2E1 microsomal protein
      followed the same enzyme activity profile from 3 to 8 months, but remained
      constant thereafter. The level of CYP2E1 mRNA did not change over the whole
      period. While the amount of proteins did not change after 8 months, their
      functionality may be affected by oxidative stress (increase in thiobarbituric
      acid reactive substances, decrease in reduced glutathione level). However, no
      changes in carbonyl protein content were observed. The decrease in CYP2E1
      activity in rats after 11 months is most probably due to post-translational
      modifications of CYP2E1 proteins. Indeed, it may be correlated with an
      accumulation of oxidative damage. Since no change was observed in CYP3A activity
      or in their protein and mRNA content, it seems that such isoforms should be less
      affected by oxidative stress.

PMID- 14600802
TI  - Pharmacogenetics of soluble sulfotransferases (SULTs).
AB  - Soluble sulfotransferases (SULTs) transfer the sulfo group from the cofactor 5'
      phosphoadenosine-3'-phosphosulfate (PAPS) to nucleophilic sites of relatively
      small acceptor molecules including various hormones and numerous xenobiotics.
      Sulfo conjugation of xenobiotics can lead to the formation of polar, excretable
      products as well as reactive, potentially mutagenic and carcinogenic metabolites.
      Ten SULT genes encoding 11 proteins have been identified in the human. They
      differ in substrate specificity and tissue distribution. Genetic polymorphisms
      have been detected in all human SULT genes. The functional significance of any
      polymorphisms that do not affect the amino acid sequence has not yet been
      studied. Non-synonymous single-nucleotide exchanges have been observed in
      SULT1A1, 1A2, 1B1, 1C1, 1C2 and 2A1. Functional consequences have primarily been
      explored using cDNA-expressed alloenzymes. Furthermore, an Arg213His polymorphism
      in SULT1A1 has a strong influence on the level of enzyme protein and activity in
      platelets, which have been widely used for phenotyping. Compared to other
      xenobiotic-metabolizing enzymes, only few studies have been conducted on
      associations of SULT genotypes with diseases and other health-related parameters.
      Statistically significant associations were observed between the SULT1A1 genotype
      (Arg213His) and age, obesity and certain neoplasias (mammary, pulmonary,
      esophageal and urothelial cancer). However, these findings require corroboration
      and specification. The association with neoplasias appears to be complex and
      varies between subgroups. This is not surprising, as SULTs are involved in the
      activation of some carcinogens, in the inactivation of other carcinogens, and the
      regulation of many hormones. It is important to study these functions of SULTs in
      more detail and to take into account the corresponding environmental and
      endogenous exposures in epidemiological studies.

PMID- 14600804
TI  - The fracture liaison service: success of a program for the evaluation and
      management of patients with osteoporotic fracture.
AB  - INTRODUCTION: Fracture care often represents the first opportunity for clinical
      management of osteoporosis; however, many patients do not receive any evaluation
      after a fracture. In Glasgow, Scotland, fewer than 10% of fracture patients
      underwent bone mineral density (BMD) testing. In an effort to better meet the
      needs of fracture patients by providing routine assessment and, where necessary,
      treatment for osteoporosis after their fracture, a novel service (The Fracture
      Liaison Service) was designed and implemented in two separate National Health
      Service trusts in Glasgow. METHODS: An agreed-upon standard of care for men and
      women 50+ years of age with fractures was established in collaboration with
      orthopedic surgeons and primary care physicians. The Fracture Liaison Service
      assumes responsibility for fracture case-finding and for assessing and performing
      diagnostic evaluations (including axial DXA), and making specific treatment
      recommendations for the secondary prevention of osteoporotic fractures. RESULTS:
      During the first 18 months of operation, more than 4,600 patients with fractures
      of the hip, wrist, humerus, ankle, foot, hand, and other sites were seen by the
      Fracture Liaison Service's osteoporosis specialist nurses. Nearly three quarters
      of these patients were considered for BMD testing; treatment was recommended for
      approximately 20% of the patients without need for BMD testing. Overall, 82.3% of
      patients who had BMD testing were found to be osteopenic or osteoporotic at the
      hip or spine. CONCLUSIONS: The Fracture Liaison Service has successfully
      identified and evaluated most patients with fractures. Only those patients who
      declined were not evaluated. The ultimate success of the program will be measured
      by the subsequent fracture experience of these patients, but clear improvements
      in diagnosing and treating low bone mineral density in patients with fracture
      have already been demonstrated.

PMID- 14600805
TI  - Disseminated tuberculosis, pulmonary aspergillosis and cutaneous herpes simplex
      infection in a patient with infliximab and methotrexate.
AB  - CASE PRESENTATION: Despite chemoprophylaxis with isoniazid a 58-year-old Creole
      patient with mild rheumatoid arthritis developed disseminated tuberculosis,
      pulmonary aspergillosis and cutaneous herpes simplex infection during treatment
      with infliximab and methotrexate. TREATMENT: The patient received antituberculous
      drugs (ethambutol, isoniazid, pyrazinamide, rifampicin), amphotericin B,
      flucytosine, and valaciclovir, along with prolonged intensive care treatment and
      mechanical ventilation. CONCLUSIONS: The present case confirms that isoniazid
      prophylaxis (300 mg once daily, during 6 months) does not protect against the
      reactivation and dissemination of latent tuberculosis. It also shows that
      combined treatment with infliximab and methotrexate may induce severe
      immunosuppression with prolonged leukocytopenia and depressed cellular immunity,
      leading to multiple opportunistic infections. Extensive diagnostic testing, early
      start of antimicrobial therapy and enteral immunonutrition, and further infection
      prevention with selective decontamination of the digestive tract may have been
      the key to a good clinical outcome.

PMID- 14600807
TI  - The relationship between labour cost per patient and the size of intensive care
      units: a multicentre prospective study.
AB  - OBJECTIVE: We examined the relationship between major ICU characteristics and
      labour cost per patient. DESIGN: Four-week prospective data collection, in which
      the hours spent by each physician and nurse on both in-ICU and extra-ICU
      activities were collected. SETTING: Eighty Italian adult ICUs. MEASUREMENTS AND
      RESULTS: The cost of the time actually spent by ICU staff on ICU patients (labour
      cost) was computed for each participating unit, by applying to the average annual
      salaries the proportions of in-ICU activity working time for physicians and
      nurses. Multiple regression analysis was used to identify ICU characteristics
      that predict labour costs per patient. Labour cost per patient was positively
      correlated with ICU mortality and patients average length of stay (slopes =0.67,
      p =0.048 and 0.09, p <0.0001, respectively). Labour cost per patient decreases
      almost linearly as the number of beds increases up to about eight, and it remains
      nearly constant above about twelve beds. The number of patients admitted per
      physician (not per nurse) increases with the number of beds (Spearman correlation
      coefficient =0.567, p <0.0001). CONCLUSIONS: Our findings suggest that ICUs with
      less than about 12 beds are not cost-effective.

PMID- 14600806
TI  - Evaluation and management of decompression illness--an intensivist's perspective.
AB  - Decompression illness (DCI) is becoming more prevalent as more people engage in
      activities involving extreme pressure environments such as recreational scuba
      diving. Rapid diagnosis and treatment offer these patients the best chance of
      survival with minimal sequelae. It is thus important that critical care
      physicians are able to evaluate and diagnose the signs and symptoms of DCI. The
      cornerstones of current treatment include the administration of hyperbaric oxygen
      and adjunctive therapies such as hydration and medications. However, managing
      patients in a hyperbaric environment does present additional challenges with
      respect to the particular demands of critical care medicine in an altered
      pressure environment. This article reviews the underlying pathophysiology,
      clinical presentation and therapeutic options available to treat DCI, from the
      intensivist's perspective.

PMID- 14600808
TI  - The effects of ICU admission and discharge times on mortality in Finland.
AB  - OBJECTIVE: Hospital mortality increases if acutely ill patients are admitted to
      hospitals on weekends as compared with weekdays. Night discharges may increase
      mortality in intensive care unit (ICU) patients but the effect of ICU admission
      time on mortality is not known. We studied the effects of ICU admission and
      discharge times on mortality and the time of death in critically ill patients.
      DESIGN: Cohort study using a national ICU database. SETTING: Eighteen ICUs in
      university and central hospitals in Finland. PATIENTS: Consecutive series of all
      23,134 emergency admissions in January 1998-June 2001. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: We defined weekend (as opposed to weekday) from
      1600 hours Friday to 2400 hours Sunday and "out-of-office" hours (as opposed to
      "office hours") from 1600 hours to 0800 hours. Mortality was adjusted for disease
      severity, intensity of care, and whether restrictions for future care were set.
      ICU-mortality was 10.9% and hospital mortality 20.7%. Adjusted ICU-mortality was
      higher for weekend as compared with weekday admissions [odds ratio (OR 1.20) 95%
      CI 1.01-1.43], but similar for "out-of-office" and "office hour" admissions (OR
      0.98, 0.85-1.13). Adjusted risk of ICU death was higher during "out-of-office"
      hours as compared with office hours (OR 6.89, 5.96-7.96). The time of discharge
      from ICU to wards was not associated with further hospital mortality.
      CONCLUSIONS: Weekend ICU admissions are associated with increased mortality, and
      patients in the ICU are at increased risk of dying in evenings and during
      nighttime. Our findings may have important implications for organization of ICU
      services.

PMID- 14600809
TI  - Citrate vs. heparin for anticoagulation in continuous venovenous hemofiltration:
      a prospective randomized study.
AB  - OBJECTIVE: To compare the efficacy and safety of adjusted-dose unfractionated
      heparin with that of regional citrate anticoagulation in intensive care patients
      treated by continuous venovenous hemofiltration (CVVH). DESIGN AND SETTING:
      Prospective, randomized, clinical trial in a 32-bed medical and surgical ICU in a
      university teaching hospital. PATIENTS: ICU patients with acute renal failure
      requiring continuous renal replacement therapy, without cirrhosis, severe
      coagulopathy, or known sensitivity to heparin. INTERVENTIONS: Before the first
      CVVH run patients were randomized to receive anticoagulation with heparin or
      trisodium citrate. Patients eligible for another CVVH run received the other
      study medication in a cross-over fashion until the fourth circuit. MEASUREMENTS
      AND RESULTS: Forty-nine circuits (hemofilters) were analyzed: 23 with heparin and
      26 with citrate. The median lifetime of hemofilters was 70 h (interquartile range
      44-140) with citrate anticoagulation and 40 h (17-48) with heparin (p=0.0007).
      One major bleeding occurred during heparin anticoagulation and one metabolic
      alkalosis (pH=7.60) was noted with citrate after a protocol violation.
      Transfusion rates (units of red cells per day of CVVH) were, respectively, 0.2
      (0.0-0.4) with citrate and 1.0 (0.0-2.0) with heparin (p=0.0008). CONCLUSIONS:
      Regional citrate anticoagulation seems superior to heparin for the filter
      lifetime and transfusion requirements in ICU patients treated by continuous renal
      replacement therapy.

PMID- 14600810
TI  - Can peripheral venous pressure be interchangeable with central venous pressure in
      patients undergoing cardiac surgery?
AB  - OBJECTIVE: Pressure measurements at the level of the right atrium are commonly
      used in clinical anesthesia and the intensive care unit (ICU). There is growing
      interest in the use of peripheral venous sites for estimating central venous
      pressure (CVP). This study compared bias, precision, and covariance in
      simultaneous measurements of CVP and of peripheral venous pressure (PVP) in
      patients with various hemodynamic conditions. DESIGN AND SETTING: Operating room
      and ICU of a tertiary care university-affiliated hospital. PATIENTS: Nineteen
      elective cardiac surgery patients requiring cardiopulmonary bypass were studied.
      INTERVENTIONS: A PVP catheter was placed in the antecubital vein and connected to
      the transducer of the pulmonary artery catheter with a T connector. Data were
      acquired at different times during cardiac surgery and in the ICU. MEASUREMENTS
      AND RESULTS: A total of 188 measurements in 19 patients were obtained under
      various hemodynamic conditions which included before and after the introduction
      of mechanical ventilation, following the induction of anesthesia, fluid infusion,
      application of positive end expiratory pressure and administration of
      nitroglycerin. PVP and CVP values were correlated and were interchangeable, with
      a bias of the PVP between -0.72 and 0 mmHg compared to the CVP. CONCLUSIONS: PVP
      monitoring can accurately estimate CVP under various conditions encountered in
      the operating room and in the ICU.

PMID- 14600811
TI  - Endovascular hypothermia for heat stroke: a case report.

PMID- 14600812
TI  - The prognostic value of transcranial Doppler studies in children with moderate
      and severe head injury.
AB  - OBJECTIVE: To assess the potency of transcranial Doppler (TCD) to predict
      prognosis in children with moderate and severe head trauma. DESIGN AND SETTING:
      Prospective single-center study in a level I pediatric trauma center. PATIENTS:
      Thirty-six consecutive patients with a prehospital diagnosis of moderate or
      severe head trauma admitted over a 6-month period. INTERVENTIONS: On arrival in
      the emergency room, TCD was performed and peak systolic velocities, end-diastolic
      velocity and time-averaged mean velocity in the middle cerebral artery were
      recorded. Pulsatility and resistance index were calculated. The Pediatric Trauma
      Score (PTS), Glasgow Coma Scale (GCS) score and Injury Severity Score (ISS) were
      also calculated. Patient neurological outcome was determined using the Glasgow
      Outcome Scale (GOS) at discharge from hospital. GOS 1-2 were considered as "good
      prognosis" (group 1) and GOS 3-5 were considered as "poor prognosis" (group 2).
      RESULTS. Compared with group 1 patients, group 2 patients had a significantly
      lower mean GCS (5+/-3 vs 8+/-4, p<0.05) and PTS (2+/-2 vs 5+/-2), and a higher
      mean ISS (32+/-8 vs 19+/-11, p<0.05). An end-diastolic velocity less than 25 cm/s
      and a pulsatility index more than 1.31 were associated with a poor prognosis
      (p<0.05). CONCLUSION: In children with moderate and severe head trauma, our data
      suggest an association between the results of TCD assessment on arrival in the
      emergency room and the outcome at discharge from the hospital.

PMID- 14600813
TI  - Effects of recurrent antecedent hypoglycaemia and chronic hyperglycaemia on
      brainstem extra-cellular glucose concentrations during acute hypoglycaemia in
      conscious diabetic BB rats.
AB  - AIMS/HYPOTHESIS: Our aim was to determine whether the divergent effects of
      chronic exposure to hyperglycaemia or hypoglycaemia on the glycaemic threshold
      for auditory brainstem dysfunction are reflected in the extra-cellular fluid
      (ECF) concentrations of glucose in the inferior colliculus during hypoglycaemia
      in the diabetic BB rat. METHODS: Microdialysis was used to measure inferior
      colliculus ECF glucose concentrations under basal and hyperinsulinaemic (20
      mU/kg.min) hypoglycaemic conditions. RESULTS: ECF glucose is increased under
      basal (hyperglycaemic) conditions and decreases during hypoglycaemia in both
      recurrently hypoglycaemic and chronically hyperglycaemic diabetic BB rats (to
      0.5+/-0.1 and 0.8+/-0.2 mmol/L respectively), with no significant differences
      between groups. In both groups the plasma to ECF glucose ratio doubled during
      hypoglycaemia. CONCLUSION/INTERPRETATION: Prior exposure to recurrent
      hypoglycaemia does not lead to increased ECF glucose concentrations in the
      inferior colliculus of diabetic BB rats. The resistance to impaired brainstem
      function seen in recurrently hypoglycaemic rats during hypoglycaemia cannot
      simply be attributed to increased blood-brain barrier glucose transport within
      this brain region.

PMID- 14600814
TI  - Change in patients' body weight after 12 months of treatment with glimepiride or
      glibenclamide in Type 2 diabetes: a multicentre retrospective cohort study.
AB  - AIMS/HYPOTHESIS: Our study compared the effects of glimepiride or glibenclamide
      treatment on body weight over 12 months of treatment in patients with Type 2
      diabetes in routine outpatient practice. METHODS: This new retrospective study
      design used data from physicians in a restricted manner (retrolective). Data from
      case report forms from 520 patients from 91 randomly selected centres were
      assessed and covariance analysis performed. RESULTS: The influence of practice
      and patient characteristics on treatment assignment was low, reflecting the
      design of randomised controlled trials. Mean weight loss and reduction in body
      mass index from baseline to study endpoint were greater with glimepiride than
      with glibenclamide (-2.04+/-3.99 kg vs -0.58+/-3.65 kg, p<0.001; -0.71+/-1.38
      kg/m(2) vs -0.20+/-1.28 kg/m(2), p<0.001). Duration of treatment at baseline
      influenced treatment outcome, but propensity score, sex, age and fasting blood
      glucose at baseline did not. Both glimepiride and glibenclamide led to decreases
      in fasting blood glucose (-2.43+/-0.24 mmol/l vs -3.03+/-0.24 mmol/l; p<0.001 vs
      baseline) and HbA(1c) (-1.23+/-0.09% vs -1.26+/-0.09%; p<0.001 vs baseline). Both
      treatments were associated with a decrease in serum total cholesterol and low
      density lipoprotein cholesterol. Triglycerides were lower in the glibenclamide
      group and high density lipoprotein cholesterol was higher in the glimepiride
      group only. CONCLUSIONS/INTERPRETATION: Initial treatment of Type 2 diabetes with
      glimepiride was associated with a significantly greater decrease in body weight
      and body mass index than treatment with glibenclamide, while providing equivalent
      glycaemic control.

PMID- 14600815
TI  - -To: Poa NR, Cooper GJS, Edgar PF: Amylin gene promoter mutations predispose to
      Type 2 diabetes in New Zealand Maori. Diabetologia 46: 574-578.

PMID- 14600818
TI  - Importance of cerebrospinal fluid examination in differential diagnosis of
      Devic's neuromyelitis optica by multiple sclerosis.

PMID- 14600816
TI  - Global profiling of double stranded RNA- and IFN-gamma-induced genes in rat
      pancreatic beta cells.
AB  - AIMS/HYPOTHESIS: Viral infections and local production of IFN-gamma might
      contribute to beta-cell dysfunction/death in Type 1 Diabetes. Double stranded RNA
      (dsRNA) accumulates in the cytosol of viral-infected cells, and exposure of
      purified rat beta cells to dsRNA (tested in the form of polyinosinic
      polycytidylic acid, PIC) in combination with IFN-gamma results in beta-cell
      dysfunction and apoptosis. To elucidate the molecular mechanisms involved in PIC
      + IFN-gamma-effects, we determined the global profile of genes modified by these
      agents in primary rat beta cells. METHODS: FACS-purified rat beta cells were
      cultured for 6 or 24 h in control condition or with IFN-gamma, PIC or a
      combination of both agents. The gene expression profile was analysed in duplicate
      by high-density oligonucleotide arrays representing 5000 full-length genes and
      3000 EST's. Changes of greater than or equal to 2.5-fold were considered as
      relevant. RESULTS: Following a 6- or 24-h treatment with IFN-gamma, PIC or IFN
      gamma and PIC, we observed changes in the expression of 51 to 189 genes. IFN
      gamma modified the expression of MHC-related genes, and also of genes involved in
      beta-cell metabolism, protein processing, cytokines and signal transduction. PIC
      affected preferentially the expression of genes related to cell adhesion,
      cytokines and dsRNA signal transduction, transcription factors and MHC. PIC
      and/or IFN-gamma up-regulated the expression of several chemokines and cytokines
      that could contribute to mononuclear cell homing and activation during viral
      infection, while IFN-gamma induced a positive feedback on its own signal
      transduction. PIC + IFN-gamma inhibited insulin and GLUT-2 expression without
      modifying pdx-1 mRNA expression. CONCLUSION/INTERPRETATION: This study provides
      the first comprehensive characterization of the molecular responses of primary
      beta cells to dsRNA + IFN-gamma, two agents that are probably present in the beta
      cell milieu during the course of virally-induced insulitis and Type 1 Diabetes.
      Based on these findings, we propose an integrated model for the molecular
      mechanisms involved in dsRNA + IFN-gamma induced beta-cell dysfunction and death.

PMID- 14600817
TI  - Selective impairment of insulin signalling in the hypothalamus of obese Zucker
      rats.
AB  - AIM/HYPOTHESIS: By acting in the brain, insulin suppresses food intake. However,
      little is known with regard to insulin signalling in the hypothalamus in insulin
      resistant states. METHODS: Western blotting, immunohistochemistry and polymerase
      chain reaction assays were combined to compare in vivo hypothalamic insulin
      signalling through the PI3-kinase and MAP kinase pathways between lean and obese
      Zucker rats. RESULTS: Intracerebroventricular insulin infusion reduced food
      intake in lean rats to a greater extent than that observed in obese rats, and pre
      treatment with PI3-kinase inhibitors prevented insulin-induced anorexia. The
      relative abundance of IRS-2 was considerably higher than that of IRS-1 in
      hypothalamus of both lean and obese rats. Insulin-stimulated phosphorylation of
      IR, IRS-1/2, the associations of PI 3-kinase to IRS-1/2 and phosphorylation of
      Akt in hypothalamus were decreased in obese rats compared to lean rats. These
      effects seem to be mediated by increased phosphoserine content of IR, IRS-1/2 and
      decreased protein levels of IRS-1/2 in obese rats. In contrast, insulin
      stimulated the phosphorylation of MAP kinase equally in lean and obese rats.
      CONCLUSION/INTERPRETATION: This study provides direct measurements of insulin
      signalling in hypothalamus, and documents selective resistance to insulin
      signalling in hypothalamus of Zucker rats. These findings provide support for the
      hypothesis that insulin could have anti-obesity actions mediated by the PI3
      kinase pathway, and that impaired insulin signalling in hypothalamus could play a
      role in the development of obesity in this animal model of insulin-resistance.

PMID- 14600819
TI  - CT-guided stereotactic biopsies of brain stem lesions: personal experience and
      literature review.
AB  - Appropriate therapy of brain stem lesions should be guided by an accurate
      diagnosis. Clinical evaluation combined with modern neuroimaging techniques may
      nowadays approach the diagnosis but not always with accuracy, thus leading to
      erroneous treatment. We report a series of 11 patients who underwent stereotactic
      biopsy for brain stem lesions. In 8 patients, the lesion was approached
      transfrontally. In the remaining 3 patients, the lesion was approached via the
      suboccipital transcerebellar route. There was no surgical mortality. Precise
      histological diagnosis was achieved in all patients. Three patients (27.2%)
      suffered complications attributed to the procedure and were successfully treated
      conservatively. Histological results were in accordance with preoperative
      diagnosis in 9 patients (81.8%). Despite the limited number of patients, our data
      suggest that stereotactic biopsy of brain stem lesions is a safe technique that
      can obtain adequate tissue for histological diagnosis, thus providing each
      patient with the best available treatment.

PMID- 14600820
TI  - MMPI personality profiles in patients with primary chronic daily headache: a case
      control study.
AB  - We assessed the psychological profile of a large sample of patients with chronic
      daily headache (CDH) seen in tertiary care. We used a case-control design to
      study 791 patients who fell into the following categories: ARH group, chronic
      migraine with analgesic overuse (analgesic rebound headache, ARH), n=399; CM
      group, chronic migraine (CM) without analgesic overuse, n=158; and new daily
      persistent headache (NDPH) group, n=69. These groups were compared to two control
      groups: 1, migraine, n=100; 2, chronic posttraumatic headache (CPTH), n=65. We
      assessed personality and psychopathology with the Minnesota multiphasic
      personality inventory (MMPI)-2. The number of patients with Tscores > or =65 and
      < or =40 were analyzed by the two-sided Fischer's exact test. The ARH and CM
      groups had a higher number of subjects with T-scores > or =65, when compared to
      the migraine group, on the following scales: 1 (hypochondrias), 2 (depression), 8
      (schizophrenia) and 0 (social introversion). No differences were observed between
      the NDPH and migraine groups. Considering CPTH as the control group, the pattern
      we found was quite the opposite of that described above: NDPH group presented a
      higher number of subjects with T-scores > or =65 on the following scales: 1, 2, 7
      (psychasthenia) and 8. ARH and CM groups had significantly higher T-scores for
      scale 7 alone. NDPH showed T-scores < or =40 in scale 9 when compared to both
      control groups. We conclude that: (1) psychopathological factors are common in
      CDH patients, and appear to be a consequence of the chronification process; (2)
      low scores on scale 9 (hypomania) may relate to the development of NDPH; (3)
      psychopathological profiles differ among the subgroups of CDH and the MMPI-2 is
      reliable in identifying such patterns; and (4) psychological assessment is an
      essential step in the evaluation and treatment of patients with CDH.

PMID- 14600821
TI  - Electromagnetic waves of 900 MHz in acute pentylenetetrazole model in ontogenesis
      in mice.
AB  - The purpose of this study was to measure the effects of electromagnetic waves
      (EMW) at 900 MHz. EMW were produced by a signal generator and were administered
      to mice via an antenna. The frequency of the waves was tested by a spectrum
      analyser and a frequency-meter. The emitted power was 0.25 mW. A total of 117
      mice (59 prepubertal and 58 adult) was used. Mice were exposed to EMW or sham
      radiation for 2 h and 20 h before an injection of pentylenetetrazole (PTZ). A
      statistically significant difference was found between the latency measurements
      within 20 h for prepubertal mice in stages 1 and 2 ( p<0.05). The effects on
      prepubertal mice of long-term 900 MHz EMW in a PTZ model may be an indication of
      possible problems in developing brains.

PMID- 14600822
TI  - Interleukin-18 in acute ischaemic stroke patients.
AB  - As proinflammatory cytokines released during ischaemia are detrimental to the
      brain, the study aimed to evaluate serum interleukin-18 (IL-18) levels in stroke
      patients and to investigate the relation between these and epidemiological and
      clinical data. The study comprised 23 ischaemic stroke patients and 15 controls.
      Blood sampling for IL-18 determination and for chemistry, and brain CT were
      performed within 24 h of stroke, while neurological stroke severity and
      functional disability were estimated, respectively, with the Scandinavian stroke
      scale (SSS) and Barthel index (BI) within the same interval and two weeks later.
      There were higher serum IL-18 levels in stroke patients. These correlated with
      erythrocyte sedimentation rate (ESR), brain CT hypodense area volumes, and SSS
      and BI scores calculated at both studied times. Moreover, IL-18 levels were
      higher in patients with non-lacunar stroke subtype than in those with lacunar
      strokes. The results suggest that IL-18 is involved in stroke-induced
      inflammation and that initial serum IL-18 levels may be predictive of stroke
      outcome.

PMID- 14600823
TI  - Legal and assistance aspects of Alzheimer's disease: analysis of 100 cases.
AB  - Caring for patients with disabling cognitive diseases, such as Alzheimer's
      disease (AD) and other progressive dementias, has a number of legal and social
      welfare implications. The two main problems to be discussed with patients and
      caregivers are the need for a legal guardian and requests for government
      financial support, both of which depend on the patient's progressive loss of
      autonomy and increasing need for assistance. In order to study the presence of
      these two support measures, we considered 100 AD patients (56 women and 44 men)
      divided in four groups on the basis of the stage of the disease: mild (25),
      moderate (34) and severe (32), or death (9). We investigated the number of
      caregivers for each patient (and their relationship with the patient), the
      presence of a legal guardian, and whether government financial support had been
      obtained. The number of caregivers increased for each patient as the disease
      advanced (54% with moderate and 67% with severe disease had > or =1 caregiver),
      but only 11% of the patients had a guardian. The caregivers were most likely to
      be family members (70% were spouses, 45% offspring). Only 23% of the patients
      with moderate and 62% with severe disease received government financial support.
      Our data concerning the care of incompetent people (as AD patients progressively
      become) in juridical (guardianship/trusteeship/proxy/power of attorney) and
      social terms (government financial support) show that such aspects are not
      sufficiently taken into account until the patients reach a severe disease or have
      died.

PMID- 14600824
TI  - Neuromyelitis optica: importance of cerebrospinal fluid examination during
      relapse.
AB  - Devic's neuromyelitis optica (NMO) is a clinical entity characterised by severe
      transverse myelitis, optic neuropathy and monophasic or recurrent course. We
      report the case of a woman affected by myelitis and optic neuritis suggesting
      Devic's disease. Diagnosis was supported by clinical, neuroradiological and
      biochemical findings. In 14 months, the patient developed 5 clinical
      exacerbations. Six cerebrospinal fluid (CSF) examinations were performed, 3
      during relapses and 3 during remitting phases: all the CSF specimens obtained
      during relapses showed granulocyte pleocytosis and increased protein level,
      whereas CSF was normal during stationary phases. Oligoclonal banding was always
      absent. Spinal cord MRI showed altered signal at cervical and thoracic levels. We
      did not find any concomitant systemic disease. The case we report underlines the
      importance of CSF examination during clinical relapse in NMO diagnosis.

PMID- 14600825
TI  - Association of spondylocostal dysostosis and type I split cord malformation.
AB  - In reports on children with congenital segmental costovertebral malformations who
      showed neural tube defects, cases with type I split cord malformation are quite
      rare. Up to now such association has been reported only in two cases with Jarcho
      Levin syndrome. Here, a 7-year-old girl presenting with spondylocostal dysostosis
      and type I split cord malformation is reported. To the best of our knowledge,
      this is the first case documented in the literature. The association of segmental
      costovertebral malformations and neural tube defects is discussed. Genetic and
      embryological studies are also briefly reviewed.

PMID- 14600826
TI  - Use of antiparkinsonian drugs in the Umbria Region.
AB  - Discussion of differences between recommended guidelines and clinical practice is
      very useful in medicine. The use of a computerized database of all prescriptions
      of antiparkinsonian drugs enabled us to perform an epidemiological population
      based study with low cost and in a relatively short time. We have identified 2
      827 parkinsonian patients in November 2000 and estimate the number of patients
      taking dopaminoagonists aged >75 years, antidepressive drugs, and atypical
      neuroleptics.

PMID- 14600827
TI  - Association of tau gene polymorphism with Parkinson's disease.
AB  - We investigated the segregation of the dinucleotide GT repeat polymorphism in the
      intron between exons 9 and 10 of the tau gene in 300 patients with Parkinson's
      disease (PD) and in 197 normal controls. The A3 allele was more frequent in cases
      than in controls (30% versus 16%, p<0.001), and individuals carrying at least one
      A3 allele in their genotype had an increased risk of developing PD (odds ratio
      2.78, 95% confidence interval 1.81-4.29). No significant differences were found
      between patients by considering the age at onset and the presence of family
      history or dementia. Our findings suggest a possible involvement of the tau gene
      in the pathogenesis of PD.

PMID- 14600828
TI  - Fatigue in Parkinson's disease.
AB  - Fatigue is a recognized problem in Parkinson's disease and other clinical
      conditions. We characterized this symptom in 19 patients and 19 age- and sex
      matched controls, using the Multidimensional Fatigue Inventory (MFI) and the
      Geriatric Depression Scale. Fatigue may be an independent symptom in Parkinson's
      disease, frequently associated with depression. Our analysis showed the
      usefulness of the MFI in discriminating between different dimensions of fatigue
      for a better therapeutic approach.

PMID- 14600829
TI  - Identification of transcripts from a subtraction library which might be
      responsible for the mild phenotype in an intrafamilially variable course of
      Duchenne muscular dystrophy.
AB  - While frame-shift mutations are usually found in Duchenne muscular dystrophy
      (DMD), in-frame mutations are associated with the less severe phenotype of
      Becker's muscular dystrophy. Exceptions have been reported in both directions
      suggesting the existence of modifying genes, which might be helpful for
      innovation of new therapeutic strategies. We report on the very rare case of an
      intrafamilially different course of DMD, with the younger brother being far less
      affected than the older one when compared at the same age. In this context, we
      constructed a subtraction library enriched for transcripts over-expressed in the
      patient with the milder phenotype. Twelve random clones were sequenced, followed
      by database analysis. Six of them, casein kinase 1 alpha 1, RAP2B, dynactin 3
      light chain, core binding factor beta, myosin light polypeptide 2 and one
      hypothetical gene, were further analysed by real-time RT-PCR. All these genes
      were over-expressed 3-20 times in the less affected patient compared with the
      more severely affected one. Casein kinase 1 and the hypothetical gene showed even
      a slightly higher expression than the control. Up-regulation of myosin light
      polypeptide 2, one of the most sensitive markers of muscle fibre regeneration,
      obviously reflects the milder phenotype. Casein kinase 1, dynactin and core
      binding factor are supposed to be involved in cell cycle pathways. RAP is a
      component of the signalling network which controls fundamental cellular processes
      such as proliferation and differentiation. All four might be interesting
      candidates for a therapeutic approach to diminish progression of dystrophy in
      DMD.

PMID- 14600830
TI  - Twofold symmetries in nucleotide distribution in large domains of Saccharomyces
      cerevisiae Chromosome I.
AB  - Single stranded chains of biological DNA show a widespread occurrence of parity
      for complementary nucleotides, i.e., A=T, G=C. This has been referred to as A-T,
      G-C symmetry. A distinction must be made between this, which this paper calls
      mirror symmetry, and twofold symmetry, where complementary nucleotide parity
      occurs between two segments, of the same length and equidistant from a symmetry
      center, along a single-stranded DNA chain. I have analysed the sequence of
      Chromosome I of Saccharomyces cerevisiae for the occurrence of complementary
      nucleotide symmetry. Open reading frame (ORF) sequences made up 63% of the total
      chromosome length and most of them were asymmetric for both A-T and G-C. The sign
      of A-T asymmetry was correlated with transcriptional orientation (A>T for sense
      and A<T for antisense ORFs), whereas G-C asymmetry was not. However, long single
      stranded segments of Chromosome I were A-T mirror symmetric because they
      contained similar frequencies of ORFs in both transcriptional orientations. The
      same results were obtained with the AA-TT pair of complementary dinucleotides.
      Profiling of AA-TT symmetry along Chromosome I showed this chromosome to be
      organized as a succession of five domains that were twofold symmetric for AA-TT,
      placed between two subtelomeric regions without clear symmetry properties. This
      pattern was destroyed when ORF sequences were randomly repositioned along the
      chromosome. Based on the above findings, an architectural model is proposed for
      Chromosome I, in which the twofold symmetric domains, from 30 to 50 kb long,
      correspond to chromosome loops.

PMID- 14600831
TI  - Protection of mice infected with Plasmodium berghei by Bacillus thuringiensis
      crystal proteins.
AB  - Eight Bacillus thuringiensis strains were used to test their activity against
      Plasmodium berghei. When crystal proteins extracted from strains 007, 017, 020,
      021, 030, 032, and 037 were injected into plasmodium-infected mice through the
      tail vein at a rate of 0.45-1.5 mg per mouse, the lengths of survival for the
      mice were extended up to 5 days (from 8.5 days to 13.5-15 days). Blood-cell
      staining demonstrated that normal erythrocytes were lightly stained and regularly
      shaped while the erythrocytes from plasmodia-infected mice swelled, lost shape
      and even lysed. This means that the crystal proteins could protect erythrocytes
      from the plasmodium's attack. Proteins analysis revealed that most of the
      proteins are homologues of classic crystal proteins, with the exception of the
      120-kDa protein of strain 020, a surface-layer protein. This study suggested a
      novel way to control plasmodial infections and even malaria.

PMID- 14600832
TI  - Determination of vascular endothelial growth factor (VEGF) overexpression in soft
      tissue sarcomas and the role of overexpression in leiomyosarcoma.
AB  - PURPOSE: To evaluate the prevalence and role of vascular endothelial growth
      factor (VEGF) overexpression in soft tissue sarcoma (STS). PATIENTS AND METHODS:
      VEGF expression was detected by the avidin-biotin-complex method using Santa Cruz
      biotechnology (SC 7629). The expression of VEGF was assessed according to the
      percentage of immunoreactive cells: more than 10% of the cells staining were
      graded as positive. No detectable staining or <10% (of cells) staining was graded
      as negative. RESULTS: Two hundred and seventy-three patients (164 females and 109
      males) with a mean age of 56 years (range: 1-93 years) were included in the
      study. Sixty-eight of the 273 (24.91%) patients diagnosed with STS between 1986
      and 2001 revealed VEGF overexpression. VEGF overexpression was predominantly seen
      in 30% (15/50) of patients with malignant fibrous histiocytoma (MFH), 20.45%
      (9/44) of dermatofibrosarcomas (DFS), 25% (9/36) of leiomyosarcomas (LMS), and
      30% (6/20) of patients with carcinosarcomas (CS). Despite overexpression being
      seen in about a quarter of patients with STS, VEGF overexpression was of
      prognostic value in only those patients with the LMS histologic type, as VEGF
      overexpression was associated with a shorter survival in this subgroup( P=0.01,
      by log-rank sum test). CONCLUSION: Twenty-four point nine percent of STS
      overexpress VEGF and interestingly there is diversity seen in VEGF expression
      amongst the various histologic subtypes of STS. LMS, CS, and MFH are more likely
      to reveal overexpression of VEGF than the other histologic subtypes. There was no
      relationship between survival and VEGF status in any subtype of STS, except LMS.
      There is an urgent need for larger studies to validate our findings. In addition,
      randomized clinical trials evaluating the efficacy of angiogenesis inhibitors in
      soft tissue sarcomas, especially LMS, are warranted.

PMID- 14600833
TI  - Postnatal development of cholinergic afferents from the pedunculopontine
      tegmental nucleus to the lateralis medialis-suprageniculate nucleus of the feline
      thalamus.
AB  - The lateralis medialis-suprageniculate nuclear complex (LM-Sg) has been shown to
      receive cholinergic fibers from the pedunculopontine tegmental nucleus (PPT). The
      majority of terminals of these cholinergic fibers make simple synaptic contact
      with dendritic profiles, whereas some make contacts with the dendrites of
      projection neurons and GABAergic interneurons forming a glomerular synaptic
      complex. In the present study, we investigate the postnatal development of
      glomerular synaptic complexes in the LM-Sg in association with terminals of the
      PPT-thalamic projection fibers. We examined the postnatal development of
      cholinergic innervation as well as GABAergic interneuron innervation in the LM-Sg
      using antibodies against ChAT and GABA, respectively. Although choline
      acetyltransferase (ChAT)-positive neurons already exist in the PPT at birth (P0),
      ChAT-positive fibers in the LM-Sg were observed only after P7. These ChAT
      positive fibers gradually increased in number, and almost reached the adult level
      by postnatal day 28 (P28). GABA-positive interneurons were scattered throughout
      the LM-Sg at P0, increased in size gradually and reached adult size by P14.
      Immature glomerulus-like synaptic arrangements appeared at P14. Definite
      glomeruli, in which ChAT-positive terminals are present, were observed at P28.
      These results emphasize that interneurons in the LM-Sg grow by P14, and then make
      neural circuits with cholinergic innervation within the glomerulus by 3-4 weeks.

PMID- 14600834
TI  - The slow wound-response of gammaVPE is regulated by endogenous salicylic acid in
      Arabidopsis.
AB  - Vacuolar processing enzyme (VPE) is a cysteine protease responsible for the
      maturation of various vacuolar proteins in higher plants. The Arabidopsis
      thaliana (L.) Heynh. gammaVPE gene, encoding a VPE homologue, is slowly up
      regulated in both local and systemic leaves in response to wounding. To clarify
      the activation mechanism of gammaVPE, we examined the accumulation of gammaVPE
      mRNA after hormone treatments or after wounding in wild-type and various mutant
      plants of Arabidopsis. Both ethylene and jasmonic acid (JA) are known as signal
      molecules that activate the wound-responsive genes. However, treatment with
      exogenous JA had little effect on the gammaVPE response, although JA activated
      the vegetative storage protein ( VSP) gene, a typical wound-responsive gene.
      Wounding activated gammaVPE even in two ethylene-insensitive plants (etr1-1 and
      ein2-1). Thus, the wound-induced expression of gammaVPE was independent of
      ethylene and JA. We found that the wound-induced expression of gammaVPE was
      reduced in two SA-deficient plants (pad4-1 and NahG), while the wound-induced
      expression of VSP increased in these mutants. Appreciable accumulation of SA was
      not observed in either the local or systemic leaves after wounding. These results
      suggest that endogenous SA enhances the wound-induced expression of gammaVPE and
      attenuates the wound-induced expression of VSP, although SA is not a wound-signal
      that directly activates these genes.

PMID- 14600835
TI  - Results of common laboratory tests in solvent-exposed workers.
AB  - OBJECTIVES: The screening and identification of occupational liver or other organ
      system injury related to long-term, low-level solvent exposure are difficult in
      clinical practice. We studied the feasibility of the use of common laboratory
      tests combined with a detailed exposure history. METHODS: The relationships
      between laboratory tests and exposure to organic solvents were studied in
      regression modelling adjusted to age, alcohol consumption, gender and body mass
      index (BMI). The subjects were 29 solvent-exposed workers and 19 referents.
      Laboratory tests included serum alanine aminotransferase (ALT), aspartate
      aminotransferase (AST), gamma-glutamyl transferase (GGT), carbohydrate-deficient
      transferrin (CDT), alkaline phosphatase (ALP), creatinine, cholesterol, HDL
      cholesterol, triglycerides, blood glucose and total and conjugated bilirubin.
      Positive hepatitis serology, systemic diseases or medications with known hepatic
      effects and current pregnancy were exclusion criteria. The main exposures of each
      subject were identified. Current solvent exposure status, exposure during the
      past 3 months, exposure during the past 5 and 10 years, and total life-time
      exposure were recorded. RESULTS: AST (P=0.0031), ALT (P=0.0015) and cholesterol
      (P=0.0110) correlated positively with cumulative solvent exposure in the past 5
      years, total bilirubin with current exposure (P=0.0380), and glucose with
      exposure in the past 5 (P<0.0001) and 10 (P=0.0003) years. Triglycerides
      correlated positively with exposure in the past 5 (P=0.0025) and 10 (P=0.0059)
      years and with life-time exposure (P=0.0005). Creatinine correlated negatively
      with exposure in the past 10 years (P=0.0300) and life-time exposure (P=0.0005).
      Most laboratory values were within the normal range. CONCLUSIONS: These results
      suggest a multi-system health effect of solvents. The laboratory data had some
      similarities with those in the metabolic syndrome. The screening and diagnostics
      of solvent-related conditions should be based on a thorough work history and a
      set of carefully selected laboratory tests. No single test seems sufficient for
      this purpose.

PMID- 14600836
TI  - Human osteoclasts express different CXC chemokines depending on cell culture
      substrate: molecular and immunocytochemical evidence of high levels of CXCL10 and
      CXCL12.
AB  - Chemokines are important mediators of chemotaxis, cell adherence, and
      proliferation and exert specific functions in bone remodeling. Despite the
      potential intriguing role of chemokines in the regulation of osteoclast (OC)
      functions, little is known about the expression of chemokines and their receptors
      in human OCs at different stages of differentiation. Therefore, we analyzed the
      expression of CXC chemokine receptors (CXCR1, CXCR2, CXCR3, CXCR4 and CXCR5) and
      ligands (CXCL8, CXCL10, CXCL12 and CXCL13) both at molecular and protein levels,
      in human OCs grown on plastic or calcium phosphate-coated slides at different
      stages of differentiation. Real-time PCR showed that CXCR1, CXCR2, CXCR3, CXCR4,
      CXCR5 and CXCL8 were expressed in undifferentiated cells and significantly
      decreased during OC differentiation. By contrast, CXCL10 and CXCL12 were strongly
      upregulated from day 0 to day 8 in cells grown on calcium phosphate-coated
      slides. Immunocytochemistry showed that OCs grown on plastic expressed CXCR3,
      CXCR4, CXCR5, CXCL8 and CXCL12, while they were negative for CXCR1, CXCR2 and
      CXCL10. Interestingly, both at molecular and protein levels CXCL10 and CXCL12
      significantly increased only when cells were differentiated on calcium phosphate
      coated slides. These data suggest that the selection of a substrate that better
      mimics the tridimensional structure of bone tissue, thus favoring OC maturation
      and differentiation, may be necessary when studying osteoclastogenesis in vitro.

PMID- 14600837
TI  - Effects of hypoxia and intracellular iron chelation on hypoxia-inducible factor
      1alpha and -1beta in the rat carotid body and glomus cells.
AB  - The present investigation provides for the first time, unambiguous information on
      the occurrence of hypoxia-inducible factors (HIF-1alpha and HIF-1beta proteins)
      in normoxia (Nx) and their interaction with hypoxia (Hx) and intracellular Fe(2+)
      chelation in the rat carotid body (CB) glomus cells. HIF-1alpha bound to HIF
      1beta translocated into the nucleus is identified on the basis of
      immunohistochemistry and immunofluorescence. In Nx, a weak expression of HIF
      1alpha was observed in CB glomus cells. However, exposure of CB and glomus cells
      to Hx (Po(2) approximately 7 Torr) and Nx with ciclopirox olamine (CPX, 5 microM)
      for 1 h showed a significant ( P<0.001) increase in HIF-1alpha protein. The CBs
      and glomus cells exposed to Nx, Hx, and Nx with CPX showed a constant level of
      HIF-1beta protein expression. HIF-1alpha subunit is continuously synthesized and
      degraded under normoxic conditions, while it accumulates rapidly following
      exposure to low oxygen tensions. Hydroxylation of HIF-1alpha by prolyl
      hydroxylase for proteasomal degradation was dependent on iron, 2-oxoglutarate,
      and oxygen concentration. The intracellular iron that acts as a cofactor for
      prolyl hydroxylase activity belongs to the labile iron pool and can be easily
      chelated. Thus, chelation of intracellular labile iron by CPX in Nx significantly
      increased HIF-1alpha in CB glomus cells. Thus, the results are consistent with
      the hypothesis that HIF-1alpha which is present in the glomus cells translocates
      to the nucleus during exposure to Hx and to CPX in Nx.

PMID- 14600838
TI  - Treating viral hemorrhagic fever.
AB  - Viral hemorrhagic fevers are illnesses associated with a number of geographically
      restricted, mostly tropical areas. Over recent decades a number of new
      hemorrhagic fever viruses have emerged. Advances in our understanding of the
      pathophysiology of these diseases have improved our initial supportive management
      and led to the recognition of several potentially useful antiviral agents. This
      review focuses on these hemorrhagic fever viruses and specifically addresses
      therapeutic aspects and recent progress that has been made in the treatment of
      these viral pathogens.

PMID- 14600839
TI  - Wound healing: future directions.
AB  - Over the years, numerous attempts have been made to accelerate the wound healing
      response, with varying degrees of success. This review covers the different
      phases of repair and attempts to highlight potential therapies, including
      modulation of re-epithelialization, granulation tissue formation and
      angiogenesis. Of the plethora of factors involved in these processes, three stand
      out as future candidates for development. Keratinocyte growth factor is
      undoubtedly a target for re-epithelialization, transforming growth factor-beta
      for matrix deposition and vascular endothelial growth factor is a prime target
      for angiogenesis. Particular emphasis is placed on angiogenesis as this offers
      perhaps the most intriguing line of therapy.

PMID- 14600840
TI  - Catechins and the treatment of breast cancer: possible utility and mechanistic
      targets.
AB  - Breast cancer is a disease that is in need of novel treatment strategies and the
      use of the catechins epigallocatechin gallate (EGCG), epigallocatechin (EGC) and
      epicatechin gallate (ECG) is currently being investigated as a potential therapy.
      The catechins reduce the proliferation of human breast cancer cells in vitro and
      decrease breast tumor growth in rodents. Furthermore, in vitro studies have
      demonstrated that the combination of EGCG and tamoxifen is synergistically
      cytotoxic to ERalpha- breast cancer cells. These results suggest that the
      catechins have significant potential in the treatment of breast cancer. The
      mechanisms of these effects are considered and the possible future development of
      these compounds is explored.

PMID- 14600841
TI  - 99mTc-fanolesomab Palatin Technologies.
AB  - 99mTc-fanolesomab is a radiolabeled imaging agent which is being developed by
      Palatin Technologies for use in the diagnosis of various infections, including
      appendicitis and osteomyelitis.

PMID- 14600842
TI  - DB-289 Immtech International.
AB  - DB-289, an oral diamidoxime prodrug of DB-75 from the University of North
      Carolina, Georgia State University, Auburn University and Duke University, is
      being developed by Immtech International as a potential treatment for
      Pneumocystis carinii pneumonia (PCP), tuberculosis, trypanosomiasis and malaria.

PMID- 14600844
TI  - [The German health care system needs a new commission of enquiry! The Hamburg
      Health Care Congress's proposals].

PMID- 14600843
TI  - [The Intersession Questionnaire--an inventory for the measurement of patients'
      processing of psychotherapy between sessions].
AB  - In the intervals between psychotherapy sessions, patients often make use of the
      experiences that they have during sessions with their therapists, but these
      "intersession processes" (ISP) have been largely neglected in psychotherapy
      research. This study presents a German version of the Intersession Experience
      Questionnaire (IEQ, Orlinsky et al. ) called the Inter-Session-Fragebogen (ISF).
      The ISF was used to study a total of 3.778 intersession intervals in 249 therapy
      episodes involving 229 patients. The factor structure of the ISF appears to be
      stable over therapy (up to 25 or even 50 sessions), and also over therapy
      settings (outpatient, day clinic, inpatient). Just as in the original American
      samples, there were evidently cross-culturally invariant factors like "Recreating
      the therapeutic situation", "Applying therapy," and "Relationship fantasies". The
      emotional qualities of ISP are assessed by two independent factors, called
      "Remoralizing emotions" and "Negative emotions" (regarding therapy). Differences
      between therapy settings are evident concerning intensity and trajectories of the
      factor scores over time.

PMID- 14600845
TI  - [Migraine--personality and coping mechanisms: a critical review].
AB  - There have been conflicting reports on the relationship between migraine and
      personality for more than 50 years. Our review of the literature on migraine and
      personality supports the hypothesis of secondary neuroticism. Stress has
      repeatedly been shown to trigger acute migraine attacks. So recent studies focus
      on specific stressful situations and coping strategies in patients with migraine.
      In the present paper we discuss five issues that may explain the conflicting
      findings: 1. Because almost all of the studies have been cross-sectional, the
      personality constellations found in the patients with migraine cannot be regarded
      as predisposing factors. 2. Frequently no differentiation is made between
      migraineurs in general and those who are patients, but a generalization cannot be
      made from those who see a physician to all migraineurs. 3. The term "specific to
      migraine" is appropriate only if patients with migraine differ not only from
      healthy control subjects but also from patients with other types of headache. 4.
      Most studies on migraine personality do not differentiate between subgroups and
      5. do not take into account the periodical course of the illness. Future studies
      should consider these findings.

PMID- 14600846
TI  - [Communication and interaction in psychosomatic education: use of standardized
      patients].
AB  - An amendment to the German medical curriculum in April 2002 will place
      communication and social skills at the centre of medical training. In addition to
      providing cognitive knowledge, psychosomatic courses offer the opportunity to
      integrate affective learning, with a focus on communication and interaction
      processes. In winter term 2001/2002 a training with standardised patients was
      implemented and evaluated as part of the psychosomatic internship of the
      Department of General Internal and Psychosomatic Medicine at the Medical Hospital
      of the University of Heidelberg. Quantitative and qualitative results showed that
      training with standardised patients is well accepted and that acceptance is
      independent of student gender, career choice, or interests. These training units
      are easy to integrate into psychosomatic practical courses. The results discussed
      here will focus on the role and importance of various elements of medical
      training.

PMID- 14600847
TI  - [Treatment of psychological disorders by the family doctor].
AB  - The authors investigated 191 patients with psychological disorders that had been
      treated exclusively by their family doctor. They used a questionnaire which
      systematically replicated the Consumer-Reports-Study executed in the USA in 1994.
      The investigation came to the conclusion that only the behavior and the attitude
      of the treating doctor showed influence on the result of treatment, the
      improvement of the symptoms and the satisfaction with the treatment. A supportive
      attitude increased the chance of improvement of the symptoms and the patients'
      satisfaction clearly. In addition, patients who felt supported by their doctor
      also indicated a significantly better effectiveness of a supplementary medication
      and complained clearly less about unwanted side effects than the patients who
      felt not supported by the doctor.

PMID- 14600848
TI  - [Treatment outcome study of the stuttering therapy summer camp 2000 for children
      and adolescents].
AB  - Therapists are generally confronted with the question, to what extent results of
      randomised clinical trials with their emphasis on internal validity are relevant
      for practitioners and their unselected patients. Often results from clinical
      trials are neglected in clinical practice and the "normal" practice remains
      unstudied. In this study a therapeutic approach for stuttering has been studied
      under practice conditions, but with a maximum of methodological validity. Beyond
      the concrete study it is also discussed whether the chosen procedure can be a
      model for practice studies. Patients from age 9 to 19 participated in a
      stuttering therapy summer-camp for children and adolescents by the Austria-Self
      Aid-Initiative Stuttering. Participants were supposed to learn a more open
      handling of their stuttering and acquire basics for a fluent speech. The therapy
      concept includes elements of a fluency shaping and a stuttering modification
      therapy. The evaluation followed a panel design with two assessments before, one
      assessment after therapy and one follow-up and three types of measurement: 1.
      three videotaped speech situations, 2. four questionnaires for the participants
      and their parents, and 3. Goal Attainment Scalings (GAS). The stuttering
      frequency shows a reduction from 22.2 to 9.5 % (effect size 1.29). Follow-up
      results, GAS and all questionnaires also indicate clear improvements. Altogether,
      the Therapeutic Stuttering Summer-camp was able to reach its aims.

PMID- 14600849
TI  - [Psychic disturbances in the postpartum period: an increasing problem?].
AB  - Postpartum psychic disorders can be mainly divided into 3 groups: The so-called
      postpartum blues, the postpartum depression and the postpartum psychosis. The
      postpartum blues occurs 3 - 5 days postpartum in 50 - 70 % of deliveries mostly
      disappearing after one week without specific therapy. However, 20 - 30 % of
      patients will develop a depression in their further postpartum course so that a
      thorough evaluation concerning depression is warranted, if blues symptoms persist
      more than 2 weeks. Postpartum depression can be found in 10 - 15 % of deliveries
      and mostly occurs several weeks or months after delivery with symptoms of
      depressive mood, sleeping disorders, anxiety, loss of interest and accord and
      feelings of guilt up to suicidal ideas. In order not to misinterpret them as
      postpartum blues specific questions concerning the mood of the young mother
      during the postpartum examination - if necessary using the Edinburgh scale - are
      recommended. In patients with known risk factors for a postpartum depression (i.
      e. postpartum depression or psychosis in previous pregnancies, depression
      disorder, anxiety disorder, bipolar illness), a thorough survey is mandatory and 
      if necessary - a prophylactic treatment in cooperation with the psychiatrist.
      Less severe forms of postpartum depression can mostly be treated with
      psychotherapy and sociotherapy on an outpatient basis. In more severe cases,
      antidepressant drugs (selective serotonin reuptake inhibitors, SSRIs or some
      tricyclic drugs) are indicated. Postpartum anxiety and compulsive disorders
      respond well to psychotherapy; besides in anxiety disorders benzodiazepines are
      recommended, in compulsive disorders SSRIs. Postpartum psychoses (about 0.1 - 0.2
      %) most often occur in bipolar or schizoaffective disorders or after postpartum
      psychosis. They require a hopitalization mainly because of the danger of suicide
      and homicide toward the newborn; ideally this is performed in mother-child-units.

PMID- 14600850
TI  - [Influence of antenatal acupuncture on cardiotocographic parameters and maternal
      circulation - a prospective study].
AB  - BACKGROUND: Acupuncture as a non-evidence-based therapy modality is widely used
      in obstetrics prior to and during delivery. Thus far, only few studies
      investigated the impact of acupuncture on obstetric surveillance parameters like
      cardiotocography. The aim of this study was to control the effect of clearly
      defined acupuncture on CTG parameters. PATIENTS AND METHODS: 61 low-risk
      singleton pregnancies between 30 + 0 and 39 + 6 weeks of gestation were
      prospectively treated with acupuncture at GV 20 and ST 36 bilaterally for the
      purpose of maternal relaxation by the same investigator under CTG control. Before
      (Phase 1), during (Phase 2) and after (Phase 3) treatment the cardiotocogram was
      recorded. Controlled parameters of outcome were the Fisher score, uterine
      activity (Phase 1, 2, 3) and maternal blood pressure and pulse before (Phase 1)
      and after (Phase 2) administration of acupuncture. In a matched control group, 60
      pregnant women were monitored by an identical scheme without application of
      acupuncture and the same outcome parameters were recorded. RESULTS: : The CTG
      analysis revealed a statistically significant increase of the Fisher score as
      well as uterine activity which tended to trace back to pretherapeutic initial
      values. The systolic maternal blood pressure was found to show a statistically
      significant decrease while diastolic blood pressure and pulse frequency remained
      unchanged. In the control group, the comparison of phase 1 vs. phase 2 showed a
      statistically significant increase of the Fischer score and uterine activity.
      During phase 3 the Fischer score further increased in contrast to a statistically
      significant slight reduction of uterine activity. Maternal systolic blood
      pressure measured at the end of phase 2 was found to be statistically reduced
      while diastolic blood pressure and pulse remained unchanged. The extent of the
      systolic blood pressure reduction was markedly higher in the acupuncture group as
      compared to the control group. CONCLUSIONS: Antenatal acupuncture as a reflex
      therapy for the purpose of maternal relaxation seems to exert an influence on
      short-term alterations of the fetal activity (transient increase in terms of
      Fischer score) with reversibly increased uterine activity as detected by
      cardiotocography. Also, a slight reduction of the maternal blood pressure seems
      to be effected. The phenomena recorded in the control group (relaxation without
      supportive acupuncture treatment) revealed to be partially concordant (reversibly
      increased uterine activity, mild maternal reduction of systolic blood pressure)
      and partially discordant (persisting increase of Fischer score) as compared with
      the acupuncture group. Acupuncture seems not only to have a psychological, but
      also a short-term somatic effect with direct influence on maternal and fetal
      circulation parameters. Other established surveillance parameters and different
      points of acupuncture should be studied to further elucidate the underlying
      interaction as well as the duration of this effect.

PMID- 14600851
TI  - [Placental morphometry in pregnancies with reversed enddiastolic flow in the
      umbilical artery or fetal aorta].
AB  - BACKGROUND: Fetuses with a reversed enddiastolic flow in the umbilical artery
      and/or aorta are at risk pregnancies and show a higher incidence of perinatal
      morbidity and mortality. The aim of this study was to evaluate the pathological
      changes in the terminal villous tree in fetuses with a reverse flow in the fetal
      aorta or umbilical artery. MATERIALS AND METHODS: In this retrospective study, 16
      cases with a reverse flow in the fetal aorta or umbilical artery (Gr. 1) were
      compared with gestational age matched 16 healthy pregnant women (Gr. 2). The
      following morphometric parameters were evaluated in 50 sections in each placenta
      (1600 measurements): mean vessel diameter, volume density of the villous tissue,
      stem villi and terminal villi. Measurements were performed using a computerized
      Video Image Analysis system. RESULTS: The mean gestational age at birth was
      similar in both groups (30 + 4 weeks gestation vs. 30 + 6 weeks gestation,
      respectively, for Gr. 1 and Gr. 2). The birth weights (985 g vs. 1780 g) and the
      placental weights (216 g vs. 385 g) were significantly lower in the reverse flow
      group. There was a significant reduction in the proportion of total villous
      tissue (19 % versus 45 %) and in the diameter of tissue at the terminal villi
      (2.1 % versus 7.6 %) in the reverse flow group. Although the mean number of
      vessels at the terminal villi was lower than the control group (4.1 versus 5.6),
      the mean and total areas of the vessels were not different. CONCLUSION: Our
      observations showed a significant association between the placental morphometric
      parameters and reversed enddiastolic flow in the umbilical artery or fetal aorta.
      The reduced number of functional placental units is responsible for the
      diminished exchange function of the placental vessels in "reverse flow" cases.
      This could partially explain the adverse outcome in this clinical situation.

PMID- 14600852
TI  - [Perinatal management of triplet pregnancies from 1997 to 2001].
AB  - BACKGROUND: Because of the trend for premature birth, multifetal pregnancies are
      at high risk for neonatal morbidity and mortality. This study presents our
      perinatal management scheme and the outcome of triplet pregnancies. PATIENTS AND
      METHODS: From 1997 to 2001 we studied 31 triplet pregnancies. Their management
      consisted of cervical measurement at 20 weeks, admission from 25 weeks onwards,
      regular ultrasound examinations, intravenous tocolysis with preterm contractions
      or cervical shortening, promotion of fetal lung maturation, antibiotic therapy
      with evidence of vaginal infection, delivery by caesarean section ideally at 33
      weeks. RESULTS: In the studied group 4 triplet pregnancies were monochorionic, 6
      dichorionic, and 21 (68 %) trichorionic. 2/31 triplet pregnancies finalized in
      late abortions. Furthermore, a single and a double intrauterine death occured in
      two triplet pregnancies. 6 (21 %) of triplet pregnancies were delivered before
      the 30th week and 23 (79 %) after the 30th week of gestation (median gestational
      age 31.5 weeks, median birth weight 1545g). Neonates of trichorionic pregnancies
      in comparison to those of mono- and dichorionic pregnancies were delivered two to
      three weeks later and presented with significantly higher birth weights (1660 g
      vs. 1245 g vs. 1240 g; p = 0.001 and 0.0009, respectively). 13/84 (15.5 %) of the
      neonates showed growth retardation. In 4/84 (4.1 %) children brochopulmonary
      dysplasia or cerebral haemorrhage was observed. Only one child developed
      enterocolitis. 19 % (16/84) of neonates showed evidence of retinopathy. No
      intrauterine death occured after 28 weeks and no child died after delivery.
      CONCLUSION/DISCUSSION: With our well defined management of triplet pregnancies
      from 20 weeks onwards we reach similar gestational ages at delivery but
      remarkably lower neonatal complication rates compared to previous studies.

PMID- 14600854
TI  - [HIV in the neonate - diagnosis and therapy].

PMID- 14600853
TI  - [Severe late-onset group B streptococcal infection. A case report].
AB  - BACKGROUND: Group B Streptococcus (GBS) is a well-known cause of neonatal
      pneumonia, sepsis and meningitis. Peripartal antibiotic prophylaxis for early
      onset GBS infection is in routine use since the beginning of the last decade, but
      strategies for effective prevention of late-onset GBS infections are still
      lacking. CASE REPORT: Few hours after discharge from a non-local maternity ward a
      3-week-old boy was admitted to our hospital because of GBS meningitis with
      necrotizing encephalomalacia. Maternal mastitis, not a disease of the baby, had
      led to the first admission. DISCUSSION: Case history and negative maternal swabs
      and cultures for GBS led to the hypothesis of nosocomial infection. Screening and
      risk based peripartal antibiotic prophylaxis, better monitoring and improved
      therapeutic modalities have reduced the incidence and mortality of early-onset
      GBS infections, but peripartal prophylaxis failed to influence late-onset GBS
      infections. Up to 40 % of infants with late-onset meningitis develop neurological
      sequelae. Maternal vaccination with multivalent conjugate vaccines against GBS is
      a new strategy which may lead to passive protection of the infant. Further
      studies to examine the efficacy of vaccines are in progress.

PMID- 14600855
TI  - [Fundamentals of hearing screening in neonates (standard of care)].

PMID- 14600856
TI  - [Intensive care medicine--a never ending challenge].

PMID- 14600857
TI  - [The early history of the artificial kidney].
AB  - Only very few remember Georg Haas as the scientist who--in 1924--was the first to
      successfully conduct an extracorporal hemodialysis on a patient in Giessen. Haas
      began his experiments in 1914 shortly after joining the Medical Clinic of the
      University of Giessen. Neither protocols nor any of the set-ups were preserved
      from these early experiments. In addition, the WW1 interrupted Haas' early
      experiments between 1917-1919. Until 1923 Haas himself never mentioned his early
      experiments. "Outside circumstances" and a "shortage of materials" (hirudin)
      prevented Haas from continuing his work on hemodialysis. Also, the early trials
      had disappointing results as the experimental animals, mostly dogs, died after a
      few hours. The hirudin preparations Haas had used turned out to be toxic. While
      the toxicity of the hirudin preparations prevented the application of dialysis in
      humans early on, the war with its many cases of nephritis provided new
      inspiration to develop dialyzing techniques. Haas experimented with reed tubes,
      calf peritoneum and paper membranes. None of these worked satisfactorily. Not
      until Pregl introduced collodion tubes was the first barrier overcome. Haas
      started experimenting with collodion tubes produced by himself. However, the
      toxicity problem with the hirudin preparations remained. Haas resumed the
      hemodialysis experiments in 1923. Significantly, 1923 was the year when Necheles
      published his work describing an alleged purified leech extract. Necheles' paper
      also described American experiments that focused on dialysis in animal trials. It
      was J. Abel of Baltimore who informed Haas that purified hirudin was available.
      After learning of this availability through the American studies in 1924, Haas
      conducted his first hemodialysis on a uremic patient in late 1924. This
      experiment lasted only 15 minutes and was without complications. A second
      dialysis attempt followed in 1925 and even lasted 30 minutes. Finally, four
      further experiments followed in 1926. The turning point was the availability of
      purified heparin from 1925 on. Haas, who in 1924 conducted the first dialysis
      using hirudin, in 1927 conducted the first hemodialysis using heparin. Further
      hemodialysis treatments followed. Haas concluded: "The problem of hemodialysis is
      still in the first steps of practical application. Nevertheless it could be shown
      that hemodialysis has developed sufficiently to find applicability even in
      patients with serious kidney ailments and irritable heart...Hemodialysis was not
      only well tolerated but also brought a temporary subjective improvement. Of
      course, the technical aspects of hemodialysis still need improvement and further
      development to qualify as detoxicant therapy." A look at the early history of the
      artificial kidney and its applicability to humans reveals that J. Abel conducted
      the first hemodialysis on experimental animals. It also becomes evident that Haas
      conducted the first hemodialysis in humans. The American experiments pursued the
      quantitative optimization of the method in animal trials, while Haas' experiments
      focused on the development of a therapeutic method following the principle
      "primum nil nocere."

PMID- 14600858
TI  - [Blocking nociceptive afferents by retrobulbar bupivacaine does not decrease
      nausea and vomiting after propofol-remifentanil anaesthesia].
AB  - To test whether prophylactic neural blockade of noziceptive afferents or
      antiemetics diminutes postoperative nausea and vomiting (PONV) we studied in a
      randomised, prospective, and ouble-blind fashion 102 patients receiving
      implantation of an episcleral radioactive applicator for treatment of ocular
      malignant melanoma during remifentanil-propofol-anaesthesia. METHODS: 15 minutes
      prior to induction Dolasetron 12.5 mg (n = 18) or 50 mg (n = 20), Ondansetron 8
      mg (n = 18), Droperidol 20 microg/kg (n = 23) or NaCl 0.9 % (n = 22) were
      randomly injected i.v. Furthermore, 4-8 ml Mepivacain 2 %/Bupivacain 0.5 % (n =
      52) or saline (n = 50) were injected into the retrobulbar space after anaesthetic
      induction. Piritramid (0.1 mg/kg) was given for postoperative analgesia 30
      minutes before end of surgery. Metamizol (1 g i.v.) and Dolasetron (12.5 mg i.v.)
      were provided on request as "rescue" medications. Variables were assessed by
      standardised questioning (NRS; yes/no) before and 1, 6, and 24 hours after
      surgery. STATISTICS: Chi(2)-, Mann-Whitney-U-, Kruskal-Wallis-test and logistic
      regression analysis, p < 0.05. RESULTS: Although retrobulbar anaesthesia
      decreased ocular pain (p = 0.013) and total postoperative complaints (p = 0.017)
      the incidence of PONV was not diminished. Droperidol was the only antiemetic to
      decrease PONV significantly (p = 0.001). CONCLUSIONS: Although prophylactic
      blockade of nozizeptive afferents by retrobulbar anesthesia decreased ocular pain
      and postoperative complaints, it failed to decrease the incidence of PONV. Thus,
      PONV after ocular surgery under propofol-remifentanil anaesthesia is not
      attenuated by preoperative blockade of noziceptive afferents. In patients
      undergoing total intravenous anaesthesia with propofol-remifentanil, droperidol
      prevented PONV more effectively than the used serotonin receptor antagonists.

PMID- 14600859
TI  - [Metoclopramide and dexamethasone in prevention of postoperative nausea and
      vomiting after inhalational anaesthesia].
AB  - OBJECTIVE: Because of its complex profile of action (binding to dopamine,
      serotonin and histamine receptors), low rate of adverse effects and low cost as a
      medicinal preparation, metoclopramide is an interesting substance for the
      prophylaxis of post-operative nausea and vomiting (PONV). As a single substance
      its antiemetic effects are slight at the usual dose, so the aim was to test the
      efficacy of a combination of metoclopramide and dexamethasone for the prevention
      of PONV on a group of patients with the same operative trauma. METHOD: All
      patients (n = 204) were recruited prospectively (January-October 2002) and were
      to undergo a lumbar disc operation. The anaesthetic was administered according to
      a standard procedure as a balanced anaesthetic with fentanyl and isoflurane in
      oxygen/air. 60 min before the end of the operation, all patients were given 10 mg
      of metoclopramide and 8 mg of dexamethasone intravenously. The Wurzburg-Oulu
      Score served as an instrument for comparison, because no placebo group has been
      included. 24 hours after the operation, all patients were asked to report on
      nausea and vomiting, stating the time and the degree of discomfort
      (quantification by means of an analogue numerical scale from 0-10). The influence
      of age, height, weight, duration of the anaesthetic, operating position and
      increased dexamethasone dose was analyzed in addition to the risk factors
      according to the score. The cost analysis was based on the purchase prices of the
      hospital dispensary. RESULTS: The expected PONV incidence was 35.8%; 10% nausea
      (average intensity 4.3) and 3% emesis (4.8) was reported for the 24-hour period.
      The rescue medication (dimenhydrinate) was requested 8 times. Nausea was mainly
      during the early part of the period (0-6 hours). Of 42 patients with a history of
      PONV, 71% had no symptoms. The Odds Ratios for female sex (2.9), non-smoker
      status (2.0) and post-operative opioid administration (1.9) correspond to the
      data given in the literature; it was not possible to determine the significance
      of a history of PONV as an independent risk factor. None of the other factors
      investigated had a significant influence on PONV. For the chosen combination of
      antiemetic drugs the number-needed-to-treat is 3.9 (95% CI: 3.3-4.7). The direct
      costs of the PONV prophylaxis are 0.65 euro per patient. CONCLUSIONS: The
      metoclopramide/dexamethasone combination proved to be effective and inexpensive,
      on the basis of these findings it is used prophylactically at our hospital if
      only one PONV risk factor exists.

PMID- 14600860
TI  - [Plasma levels of ropivacaine and bupivacaine during postoperative patient
      controlled thoracic epidural analgesia].
AB  - BACKGROUND: The postoperative continuous epidural application of local
      anesthetics can cause side effects like motor blockade and systemic intoxication.
      The study was performed to evaluate the plasma levels of two local anesthetics
      and their analgesic and side effects in continuous postoperative epidural
      analgesia. METHODS: In a prospective, randomized and double-blind study we have
      compared side effects of ropivacaine 0.375% (group R) vs. bupivacaine 0.125% in
      combination with sufentanil 0.5 microg ml(-1) (group B/S) via thoracic epidural
      catheters for a duration of 96 hours after major abdominal surgery in 30
      gynaecological tumor patients. Analgesic effects, side effects and plasma levels
      of the respective local anesthetic were measured 24, 48, 72 and 96 h after start
      of epidural infusion. RESULTS: No differences were seen in demographics,
      perioperative data and analgesic effects. The following cumulative doses of local
      anesthetics were applied (Group R vs. B/S (median/minimum-maximum ml)): 24 h:
      151/121-225 vs. 141/83-171; 48 h: 311/237-424 vs. 299/184-497; 72 h: 454/366-566
      vs. 440/256-598; 96 h: 572/399-859 vs. 568/284-711. Plasma levels of local
      anesthetics remained far below the toxic threshold of 0.6 micro g/ml (Group R vs.
      B/S (median/minimum-maximum micro g/ml): 24 h: 0.05/0.03-0.24 vs. 0.0/0.0-0.02;
      48 h: 0.06/0.02-0.15 vs. 0.006/0.0-0.02; 72 h: 0.05/0.0-0.11 vs. 0.0/0.0-0.02; 96
      h: 0.02/0.01-0.32 vs. 0.0/0.0-0.01). The incidence and intensity of motor block
      (Bromage scale) and other side effects did also not differ between groups.
      CONCLUSION: The present study shows that thoracic epidural infusion with
      bupivacaine 0.125% and with a higher concentration of ropivacaine 0.375% during
      96 h provides plasma levels of unbound local anesthetic far below the toxic
      threshold.

PMID- 14600861
TI  - [New pathways and current concepts in intensive care medicine--a summary of
      important articles of the last month].
AB  - One of the most outstanding critical care concepts of the last month is the
      definition of 5 therapy strategies by the Society of Critical Care for treatment
      of patients in septic shock. These strategies are: Low tidal volume of 6 ml/kg(
      1) body weight in patients with ARDS, early goal-directed therapy, activated
      protein C therapy, moderate-dose corticosteroids, and tight control of blood
      sugar. Following further review of the main critical care medicine related
      journals for strategies to reduce mortality, the non-invasive ventilation is
      worthwhile mentioning. Moreover, this review summarizes articles on the topics
      of: Low-dose dopamine does not prevent acute renal insufficiency, increase of
      mortality is not related to albumin infusion, subglottic suctioning prevents
      early onset of ventilator associated pneumonia, prone position in ARDS patients
      has no influence on mortality, the safest site for central venous
      catheterization, and pulmonary-artery catheter directed therapy has no influence
      on mortality of high-risk surgical patients.

PMID- 14600862
TI  - [Amanita poisoning during pregnancy].
AB  - A pregnant woman at the 28th gestational week and three other members of the
      family had mushrooms for dinner. One of these mushrooms was an Amanita mushroom.
      The morning after, three of them suffered from nausea, vomiting and diarrhoea.
      The pregnant woman was admitted to hospital, and therapy with Penicillin and
      Silibinin was started immediately. Hepatic and renal blood parameters were
      observed repeatedly for early detecting of organ failure. Fetal lung maturation
      was forced by administration of betamethasone. After five days at the intensive
      care unit mother and unborn child were dismissed at normal physical condition.

PMID- 14600863
TI  - [Systemic diseases].

PMID- 14600864
TI  - Cancer imaging with radiolabelled antibodies and peptides.

PMID- 14600865
TI  - Comparison of 99mTc-alafosfalin and 67Ga-citrate in a mouse model of bacterial
      infection.
AB  - BACKGROUND: The antibiotic-peptide (99m)Tc-alafosfalin was assessed as an
      infection imaging agent in Staphylococcus aureas infected mice by comparison with
      (99m)Ga-citrate, and also examined for influence of septic status on tracer
      biodistribution by comparison with normal mice. MATERIAL AND METHODS:
      Intramuscular doses of S. aureus were administered into the right thigh muscle of
      mice and the infection was allowed to develop for 20 hours. In separate
      experiments, (99m)Tc-alafosfalin and (67)Ga-citrate were subsequently
      administered and allowed to localise. Quantitative organ distribution studies
      were performed in conjunction with scintigraphic images at 1 and 4 hours post
      injection. An additional biodistribution with (99m)Tc-alafosfalin in normal mice
      was also performed. RESULTS: (99m)Tc-alafosfalin was predominantly renal
      excreted, with low liver, intestine and bone uptake. There was no difference in
      the uptake of these organs when infected mice were compared with normal mice.
      (99m)Tc-alafosfalin activity in the intestine at 1 and 4 hours was substantially
      less than (67)Ga-citrate. For (99m)Tc-alafosfalin, infected/non-infected thigh
      ratios of 2.8/1.0 and 3.6/1.0 were determined at 1 and 4 hours post injection
      respectively. (67)Ga-citrate gave ratios of 1.6/1.0 and 3.7/1.0 at the
      corresponding time points. CONCLUSIONS: (99m)Tc-alafosfalin uptake was more rapid
      than (67)Ga-citrate, yet diffuse at the infectious sites in mice. The small and
      juvenile mouse model resulted in uptake of the phosphonic acid tracer by active
      bone growth areas which may be a disadvantage. This (99m)Tc-antibiotic peptide
      has potential as an infection imaging agent, and will be investigated further in
      another rodent infection model in the future.

PMID- 14600866
TI  - Preliminary studies with 188rhenium-tin colloid for radiation synovectomy:
      preparation, size determination, in-vivo distribution, effect and dosimetry
      studies.
AB  - BACKGROUND: Generator-produced beta-emitting radionuclides such as (188)Re are
      gaining in importance for radiosynoviorthesis because of their availability on a
      regular basis. MATERIAL AND METHODS: We prepared a (188)Re-tin colloid in a
      reaction carried out either at 100 degrees C or at room temperature (RT). The
      size of the colloid particles was measured with a laser lightscattering method,
      and their biodistribution, dosimetric aspects and therapeutic effects were
      studied in an antigen-induced arthritis (AIA) model in rabbits. (188)Re-tin
      colloid solution was injected intra-articularly into the knee joints of rabbits
      with AIA and imaging studies were performed. Blood samples were collected post
      injection for estimation of the blood residence time. We also injected 2 intact
      rabbits in the same manner with (188)Re perrhenate solution in order to observe
      its effects and distribution in the body. All the treated rabbit knees were
      subjected to histopathology. RESULTS: The colloid particle size distribution was
      different after preparation at the different reaction temperatures, with a more
      suitable mean of 4.53 micro m in the RT preparation. The dose delivered to the
      synovial surface was between 3.51 and 4.21 Gy and that to the bone surface was
      between 0.70 and 0.84 Gy. Histopathologic examination revealed the development of
      fibrous connective tissue in the AIA knees 4 weeks after treatment, but not in
      the control group. CONCLUSIONS: The (188)Re-tin colloid preparation used in this
      study was suitable for radiation synovectomy application. It requires
      modifications in the preparation protocol so as to increase the labeling
      efficiency in correlation with an appropriate particle size.

PMID- 14600867
TI  - Optimal time window for measurement of renal output parameters.
AB  - Although normalised residual activity (NORA) and output efficiency (OE) are
      usually measured at a fixed time t, their dependency on t may affect the
      prediction of mean transit time (MTT). This study aimed to evaluate their degree
      of dependency on t and to determine an optimal time of measurement by assessment
      of their relationship with MTT for various times t. A simulation model generated
      232 cortical renograms by convolving one plasma disappearance curve with 232
      created cortical retention functions. The results show that considerable changes
      are observed for NORA and OE, depending on the time of measurement t. The choice
      of this time significantly influences the predictive value of these parameters
      for estimating MTT. The optimal time for measurement of NORA and OE should be
      close to the MTT, at the moment when emptying takes place. In the clinical
      practice, it should be adapted to the clinical problem under investigation.

PMID- 14600868
TI  - Estimation of usefulness of monitoring tissue polypeptide antigen--TPA-M
      concentrations in the effectiveness surgical treatment of urinary bladder cancer.
AB  - BACKGROUND: Of all cancer tumours, urinary bladder cancer is the fourth must
      common in men and the seventh in women. The aim of this work was to answer the
      question whether tissue polypeptide antigen (TPA-M) determination in patients
      after electroresection of urinary bladder cancer can be used to establish the
      probability of tumour recurrence. MATERIAL AND METHODS: The research included 98
      patients, all of whom had undertaken electroresection of urinary bladder tumour
      (TURT), which enabled its removal, and then estimation of malignancy and
      progression stage according to the international TNM scale. The mean age was 62.7
      years. All patients had blood samples taken to determine TPA-M and then underwent
      routine cystoscopy examination. RESULTS: The patients with tumour recurrence (60,
      mean age 64 +/- 10) had TPA 30.2 +/- 4.3 U/l, the patients without recurrence
      (38, mean age 61.3 +/- 11) had TPA-M 26.2 +/- 3.18 U/l (p > 0.1). Taking the TPA
      M threshold point 85 U/l as normal, true-positive results were 16.3%, true
      negative were 31.6%, false-positive results were 7.1% and false-negative were
      44.9%. The ROC curves with the calculated area under them are the measurement of
      the diagnostic estimation of TPA-M concentrations in specificity and sensitivity
      categories. CONCLUSIONS: For the examined group the calculated P was 0.45. If P
      value is under 0.5 it is considered that the test should not be used in
      diagnosing recurrence of urinary bladder cancer.

PMID- 14600869
TI  - Early and late changes in myocardial function and heart rate variability in
      patients after myocardial revascularisation.
AB  - BACKGROUND: The purpose of the study was to evaluate the effect of myocardial
      revascularisation and associated improvement of left ventricular systolic
      function on heart rate variability in patients after myocardial infarction.
      MATERIAL AND METHODS: The study population consisted of 35 patients, who within
      the previous 6 months had suffered from myocardial infarction and in whom low
      dose dobutamine ventriculography revealed hibernating myocardium, whereas
      coronary angiography provided indications to revascularisation. CABG was
      performed in 22 patients, PTCA of the infarct-related artery in 13 patients. At
      baseline, 3 months and 3 years after the procedure radionuclide ventriculography,
      myocardial perfusion scintigraphy and 24hr continuous ECG recording were
      performed. RESULTS: After initial improvement of systolic function in
      ventriculography (EF = 48.63 +/- 11.6 v. 52.37 +/- 11.27 at p < 0.001) it
      slightly but not significantly decreased at long-term follow-up (EF = 51.8 +/-
      10.77). The remaining parameters of systolic function function behaved in a
      similar way in radionuclide ventriculography. Diastolic function parameters did
      not change significantly at early and long-term follow-up. HRV measures did not
      change at 3 months but at 3 years both sympathetic- and parasympathetic- related
      parameters and global autonomic activity were diminished. At 3 years global
      autonomic activity and parasympathetic activity were diminished with their values
      similar in both groups. CONCLUSIONS: It seems that HRV measures diminish at long-
      -term follow-up. The type of revascularisation procedure is only of short-range
      value with the parameters stabilising on a similar level at long-term follow-up.

PMID- 14600870
TI  - 111In-platelets dynamic study in chronic immune thrombocytopenic purpura.
AB  - BACKGROUND: The aim of this work was to estimate the significance of a dynamic
      study performed during the first 20 minutes after autologous (111)In-oxinate
      platelets injection in patients with chronic immune thrombocytopenic purpura
      (ITP). Two hypotheses were tested: a) dynamic study indicates the place of
      platelet sequestration; b) dynamic study reflects the quality of platelet
      separation and labelling procedure. MATERIAL AND METHODS: Thirty-nine persons
      were investigated: 25 with shortened platelet life span (ITP), and 14 with normal
      platelet life span (6 healthy subjects and eight patients with myelodysplastic
      syndrome--MDS). Platelet blood count on the day of platelet labelling, general
      yield of platelet labelling (GYL), differential yield of platelet labelling
      (DYL), platelet life span, dynamic study with initial platelet accumulation in
      the liver (IPAL), sequential static study for determining the platelet
      sequestration index (SI) and platelet sequestration site (SS) were investigated.
      RESULTS: Two types of labelled platelet kinetics were determined in both groups
      of patients: IPAL < 20% and IPAL > 20%. A statistically significant difference in
      GYL and DYL was noted between the patients with IPAL < 20% and IPAL > 20%. No
      significant difference was registered in platelet blood count, life span, SS and
      SI between the two groups of patients. Both yields of platelet labelling were
      higher in the group with IPAL < 20%. There was no correlation between IPAL and
      platelet SI, or between IPAL and platelet SS. CONCLUSIONS: Dynamic study with
      (111)In-platelets cannot predict platelet sequestration site in ITP patients, but
      it is a useful and sensitive method of platelet labelling procedure quality
      control.

PMID- 14600871
TI  - The diagnostics of recurrent gliomas using FDG-PET: still questionable?
AB  - BACKGROUND: For a number of years, FDG-PET was considered as a gold standard for
      the differential diagnosis of recurrent glioma and radionecrosis. Recently
      published papers have introduced a wealth of scepticism into this area. The aim
      of this work is to specify the added value of FDG PET, as compared to MRI, in
      terms of diagnostics of recurrent gliomas in the clinical setting of the PET
      Centre Prague. MATERIAL AND METHODS: MRI and FDG-PET were used to examine 29
      patients for suspicious glioma recurrence, after 30 open neurosurgical operations
      or re-operations combined with chemo- and/or radiotherapy. The sensitivity,
      specificity and accuracy of both examinations were calculated with respect to
      their micromorphological findings (n = 28) or the clinical and radiological
      follow-up (n = 2). RESULTS: MRI detected 23/24 tumour recurrences (sensitivity =
      95.8%) and FDG PET only 15 of these (sensitivity = 62.5%). MRI specified only 3/6
      radionecrotic lesions (specificity = 50.0%), while FDG PET identified 5/6
      (specificity = 83.3%). Overall accuracy was 26/30 (86.7%) for MRI and 20/30
      (66.7%) for FDG PET. In the subgroup of MRI positive or equivocal findings (n =
      29) FDG PET was clearly positive in 15 cases. High-grade glioma recurrence was
      subsequently confirmed in all of them. On the other hand negative or equivocal
      FDG PET was associated in 5/14 cases (35.7%) with radionecrosis, in 3/14 (21.4%)
      with low-grade glioma and in 6/14 (42.9%) with high-grade glioma. CONCLUSIONS:
      MRI is the method of choice for the detection of glioma recurrence but it is
      associated with a high rate of false positive results. FDG PET has significantly
      lower sensitivity; nevertheless it does help to specify MRI positive lesions. FDG
      PET positive lesions give a very high probability of high-grade glioma, but its
      equivocal and negative findings are of no clinical value.

PMID- 14600872
TI  - Technetium-99m MIBI imaging in diagnosis of pelvic and abdominal masses in
      patients with suspected gynaecological malignancy.
AB  - BACKGROUND: The aim of this study was to determine the diagnostic value of
      (99m)Tc MIBI planar dynamic scintigraphy in the diagnosis of gynaecological
      malignancies and to determine if it has a greater diagnostic accuracy than
      conventional ultrasound technique (US). MATERIAL AND METHODS: A prospective trial
      was performed to assess the accuracy of (99m)Tc MIBI scintigraphy and ultrasound
      in 93 female patients (mean age 50, SD 16; range 17-82 years). Three readers
      assessed all the imaging independently and this was compared with histological
      examination in 89 cases and by clinical follow-up and correlative imaging for a
      minimum of 6 months in 4 patients. RESULTS: There were 37 patients with cancer of
      gynaecological origin. There were in addition 56 benign lesions within the
      pelvis. (99m)Tc MIBI identified correctly 29 of the 37 malignant tumours
      localised within the pelvis and also correctly identified 21 of 23 metastases
      within the abdomen. Conventional US identified correctly 35 of the 37 tumours in
      the pelvis and 16 sites of metastases within the abdomen. The sensitivity and
      specificity of tumour detection within the pelvis for (99m)Tc MIBI were as
      follows: 78% and 70%; and for metastases within the abdomen 91% and 90%. The
      results of ultrasound for tumour detection within the pelvis: the sensitivity and
      specificity were 95% and 79% and for abdominal metastases 70% and 97%. Analysis
      of the index area under a receiver operator characteristic (ROC) curve in
      scintigraphy did not show a significant difference between both techniques in the
      diagnosis of pelvic lesions. There was however a significant increase in the
      sensitivity of scintigraphy (99m)Tc MIBI over US in metastases detection within
      the abdomen. CONCLUSIONS: (99m)Tc MIBI cannot be recommended for the imaging of
      pelvic cancer alone, but it may be helpful in the identification of intra
      abdominal spread of ovarian carcinoma and appears to offer significant advantages
      over ultrasound.

PMID- 14600873
TI  - Sentinel lymph node detection in canine oncological patients.
AB  - BACKGROUND: Sentinel lymph node detection was investigated in dogs with
      spontaneously occurring tumours. MATERIAL AND METHODS: In this pilot study, 24
      client-owned spontaneously tumorous dogs presented for sentinel lymph node
      detection. A multiple method was used with a nuclear medicine technique
      (injection of 99mTc human serum albumin colloid) with scintigraphy and
      intraoperative guidance, and blue dye injection. RESULTS: Of the 35 lymph nodes
      histologically demonstrated to contain metastases, 34 (97%) were found by
      radioguided surgery, which means that one would have been missed in the
      intraoperative localisation process; 31 nodes (89%) were clearly visualised in
      the gamma camera images; only 27 (77%) were blue-stained by vital dye; a mere 8
      lymph nodes (23%) were enlarged and therefore easily detectable by palpation.
      CONCLUSIONS: Data obtained from the harmless application of the sentinel node
      concept are useful for the radiopharmaceutist. The sentinel lymph node concept is
      well applicable in the veterinary clinic.

PMID- 14600874
TI  - Preliminary radiochemical and biological studies on the liposome encapsulated
      platinum-[125I]iodohistamine complex.
AB  - BACKGROUND: The platinum-iodohistamine complex with in vitro cytostatic activity
      toward colon and mammary cancer cells has been synthesised recently in our
      laboratory. The pharmacokinetics of radioactive complex analogues, labelled with
      I-131 and I-125, has been examined in murine model of spontaneous mammary
      adenocarcinoma. The present work is devoted to the examination of the potential
      use of liposomes as a carrier system for the radioactive platinum
      [*I]iodohistamine complex in vivo. MATERIAL AND METHODS: Encapsulations of the Pt
      [(125)I]iodohistamine were studied using a different molar ratio of the complex
      and liposomes with positive surface charge, as well as various incubation
      procedures. Biodistribution of the initial and the liposomal form of the complex
      were studied in C3H tumour-bearing mice with spontaneously developed and
      transplantable (16C) mammary adenocarcinoma. RESULTS: Comparative biodistribution
      studies in C3H/16C mice and in mice with spontaneously developed mammary tumour
      have shown that in the former model pharmacokinetics of the Pt
      [125I]iodohistamine complex is more predictable and more similar to that observed
      for cisplatin. Therefore, the transplantable tumour model is more advantageous
      for the complex and its liposomal form evaluation. In C3H/16C mice, significant
      differences in the biodistribution between the radioactive platinum complex and
      its liposomal form were observed. The concentration of the activity in blood
      after 2 h p.i.v. was two times lower for the encapsulated complex, and the uptake
      of the radioactivity by liver, spleen, and lungs was twice as high as that
      obtained for the free Pt-[(125)I]iodohistamine preparation. The radioactivity in
      tumour was almost constant for liposomal platinum complex (ca. 2% ID/g), although
      it was two times lower compared to the initial platinum complex. CONCLUSIONS: The
      results of the present study indicate that platinum-[*I]iodohistamine can be
      efficiently incorporated into cationic liposomes (c. 40%). However, the uptake of
      the encapsulated complex by the liver and spleen macrophages demands further
      modification of the lipid membrane.

PMID- 14600875
TI  - Detection of acute gastrointestinal bleeding by means of technetium-99m in vivo
      labelled red blood cells.
AB  - BACKGROUND: Prognosis of gastrointestinal (GI) bleeding depends on the timely [3]
      and accurate [8, 18] detection of the source of bleeding and sequential surgical
      or endoscopy therapy. Scintigraphy with red blood cells (RBCs) in vivo labelled
      by means of technetium-99m hastened detection of source of GI bleeding and
      improved management of the particular disease. Gastrointestinal endoscopy is the
      method of choice for the diagnostics of bleeding from upper tract and large
      bowel. For diagnostics of bleeding from the small bowel we can use scintigraphy
      with in vivo labelled autological red blood cells if push-enteroscopy, intra
      operative enteroscopy or angiography are not available. MATERIAL AND METHODS: 31
      patients (13 men, 18 women, aged 20-91, mean 56 years) underwent this
      investigation from 1998 till 2001 at the Department of Nuclear Medicine. All
      patients had melaena or enterorrhagia associated with acute anaemia. Gastroscopy,
      colonoscopy, enteroclysis or X-ray angiography did not detect the source of
      bleeding. RESULTS: Twenty-one patients had positive scintigraphy with in vivo
      labelled RBCs--9 patients were already positive on dynamic scintigraphy, and 12
      patients were positive on static images. Scintigraphy with in vivo labelled RBCs
      was negative in 10 patients. GI bleeding stopped spontaneously in these 10
      patients with negative scintigraphy. These patients did not undergo intra-
      operative enteroscopy or surgery. The final diagnosis of the 21 patients with
      positive scintigraphy was determined in 16 patients by push-enteroscopy (6
      patients), intra-operative enteroscopy (6 patients) or by surgery (4 patients).
      Of these 16 patients the correct place of bleeding was determined by scintigraphy
      with labelled RBCs in 11 (69%) patients. Final diagnoses of our 16 patients with
      positive scintigraphy with autological labelled RBCs were: bleeding small bowel
      arteriovenous malformation (6 patients), uraemic enteritis with bleeding erosions
      in ileum and jejunum (2 patients), Osler-Rendu- Weber disease (1 patient),
      pseudocyst of the pancreas with bleeding vessel communicating to the transverse
      colon (1 patient), bleeding submucose varix in jejunum (1 patient), carcinoid of
      the ileum (1 patient), bleeding from the ileosigmoideoanastomosis six days after
      hemicolectomy for Crohn's disease (1 patient), bleeding from an ulcer close to
      the papilla of Vater (1 patient), bleeding from ulcer at jejunum after previous
      NSAIDs treatment (1 patient), bleeding inflammatory polyp at
      ileotransversoanastomosis (1 patient). GI bleeding stopped spontaneously in 5
      patients with positive scintigraphy. Therefore these patients did not undergo
      intraoperative enteroscopy or surgery and we could not determine the final
      diagnosis. CONCLUSIONS: Scintigraphy with RBCs in vivo labelled technetium- 99m
      hastened detection of the source of GI bleeding and improved management of the
      source of GI bleeding and improved management of disease.

PMID- 14600876
TI  - Effect of biventricular pacing on heart function evaluated by gated blood pool
      study in patients with end-stage heart failure.
AB  - BACKGROUND: Biventricular cardiac pacing has been used as a complementary form of
      therapy in patients with severe heart failure. The aim of this study was to
      evaluate the effect of the synchronous stimulation of both ventricles on the
      heart function measured by gated blood pool study (GBP). MATERIAL AND METHODS:
      Ten patients (9 men and 1 woman aged 53-74 years) with end-stage heart failure
      (HF) were studied. In all patients long-term biventricular pacing (BV) was
      applied. The obtained results were compared with single-chamber stimulation in 5
      patients and with sinus rhythm (SR) in 8 patients. All patients underwent
      repeated GBP with RBC labelled with 740 MBq of 99 mTc-pertechnetate. The LVEF was
      calculated according to the standard method based on the count rates. Phase
      analysis was performed with the standard method using first Fourier element.
      RESULTS: Clinically in almost all patients moderate to important symptomatic
      improvement has been observed. The analysis of LVEF values revealed that BV
      pacing resulted in significantly higher values only in comparison with SR (21.6%
      +/- 10.3 v. 20.1% +/- 10.1; p < 0.05). The phase shift between both ventricles by
      BV pacing was positive and similar to that obtained with SR and RV stimulation
      (14.0 degrees +/- 29.6 v. 13.4 degrees +/- 37.6 and 7.4 degrees +/- 26.5 v. 6.0
      degrees +/- 17.1 respectively). However, in comparison with LV pacing, BV
      stimulation revealed a change of dominant conduction abnormalities with a delay
      of RV contraction in relation to LV (9.0 degrees +/- 17.5 v. -3.0 degrees +/-
      11.4). CONCLUSIONS: Biventricular pacing results in slight improvement of LVEF in
      patients with heart failure and can be considered a promising approach in
      patients with end-stage heart failure. Synchronous stimulation of both ventricles
      not always results in decrease of interventricular shift, however that
      observation requires further studies on a larger population.

PMID- 14600877
TI  - Comparison of peritumoral and subareolar injection of Tc99m sulphur colloid and
      blue-dye for detection of the sentinel lymph node in breast cancer.
AB  - BACKGROUND: The new trend in diagnosis of the lymph node is sentinel node biopsy.
      This method has become increasingly accepted as a minimally invasive alternative
      to routine axillary dissection. Although the results of numerous studies have
      shown that sentinel node biopsy can accurately determine the axillary nodal
      status, the identification rates and false-negative rates have been variable. The
      sentinel lymph node is defined as the first node in the lymphatic basin that
      receives the primary lymphatic flow. MATERIAL AND METHODS: Between September 1998
      and August 2002 123 patients with primary operative breast cancer without
      clinical palpable axillary lymph nodes were enrolled in the study. There were two
      groups of patients according to sentinel node identification technique: 51
      patients (Group I) received parenchymal, peritumoral injection of 1.0 ml of 16
      MBq Tc(99m)-radiolabelled sulphur colloid and single intradermal injection of
      blue-dye over the tumour. The next 72 patients (Group II) received intradermal,
      periareolar one-site injection of 0.5 ml of 16 MBq Tc(99m)-radiolabelled sulphur
      colloid and blue-dye. RESULTS: Sentinel lymph node was found in 41 (80.4%) cases
      in Group I and in 67 (93.0%) cases in Group II (p = 0.028). The localisation of
      the axillary lymph node as a "hot spot" visualised by lymphoscintigraphy was
      successful in 39/51 (76.5%) cases in Group I and 67/72 (93.0%) in Group II, p =
      0.004). In both groups the success of sentinel node identification in the
      axillary region by lymphoscintigraphy was connected with sentinel lymph node
      finding during surgery (Group I: p < 0.001, Group II: p < 0.001). CONCLUSIONS:
      This study shows that intradermal, periareolar one-site injection of Tc(99m)
      radiolabelled sulphur colloid and blue-dye is superior to peritumoral 4-sites
      injections Tc(99m)-radiolabelled sulphur colloid and single intradermal injection
      of blue-dye over the tumour in sentinel lymph node identification.

PMID- 14600878
TI  - Windows programming--Maximum Intensity Projections with direct export to avi.

PMID- 14600879
TI  - Evaluation of nuclear medicine tests for the diagnosis of breast carcinoma.
AB  - In this paper, we evaluate nuclear medicine tests used for the diagnosis of
      breast carcinoma. Breast carcinoma is the most common carcinoma in women in
      Europe and its early diagnosis and treatment is important for the overall
      survival of the patients. Scintimammography technique, indications,
      contraindications and diagnostic procedures for the identification of the
      sentinel node and the axillary nodes infiltrated by tumour are described. Also,
      the use of the radiopharmaceuticals, radioactive thallium chloride-201, methylene
      diphosphonate labelled with technetium-99m, somatostatin receptors labelled with
      indium-111, diagnostic procedures with the PET camera, the labelled antibodies to
      CEA with technetium-99m and also the importance of the MRI and the US techniques
      are mentioned. These tests have greater diagnostic accuracy as compared to X-ray
      mammography, clinical examination, MRI and the US technique. Tumour markers in
      vitro are recommended for the follow- up of metastatic breast carcinoma.

PMID- 14600880
TI  - The role of sentinel node detection techniques in vulvar and cervical cancer.
AB  - The sentinel node is the first lymph node that receives the lymph drainage from
      the primary tumour. The pathological status of the sentinel node should reflect
      the histopathology of the entire regional lymph drainage area--both vulvar and
      cervical cancer spread through the lymphatic system. In gynaecological oncology
      recent studies have confirmed the utility of the sentinel node concept in vulvar
      and cervical cancer. Three techniques for sentinel node localisation are
      available. The preoperative lymphoscintigraphy and intraoperative hand-held gamma
      probe detection require the administration of the technetium-99m-labelled colloid
      around the tumour. The other method is based on the injection of the patent blue
      dye--during the surgery of the sentinel node because of the dye uptake becomes
      visible. Following detection, the sentinel lymph node can be removed separately
      and assessed with ultrastaging and immunohistochemical staining. In the early
      stages of vulvar and cervical cancer the lymph nodes metastases rate is
      relatively low--in most cases lymphadenectomy is not necessary. The determination
      of the regional lymph nodes' pathological status may limit the extent of the
      surgical treatment. The sentinel node detection rate is relatively high and
      depends on the applied technique. This technique may play an important role in
      the treatment of vulvar and cervical cancer. This paper describes the details of
      sentinel node identification and reviews the literature.

PMID- 14600882
TI  - From teaching to-self training i.e. Problem-Based Learning--a letter to the
      editor.

PMID- 14600886
TI  - Nuclear medicine technologists' training in different countries--a comparison.

PMID- 14600887
TI  - The accuracy of myocardial perfusion SPECT imaging in the evaluation of coronary
      artery disease in women and men.
AB  - BACKGROUND: The purpose of this study is to compare sensitivity, specificity and
      accuracy of myocardial perfusion SPECT for the detection of coronary artery
      disease (CAD) in women and men. MATERIAL AND METHODS: 588 patients (455 males and
      133 females, 273 after a previous myocardial infarction) underwent stress
      myocardial perfusion SPECT. The accuracy of myocardial perfusion SPECT was proved
      by coronary angiography (stenosis > 50% was considered as a CAD). RESULTS: The
      sensitivity of SPECT was slightly higher, but statistically not significant, in
      men than in women (94% versus 91%, p > 0.05). The specificity was higher in women
      than in men (93% versus 82%), but this difference was not statistically
      significant either (p > 0.05). The accuracy of SPECT was the same for both sexes
      (92%). In angiographically verified group of patients the selection bias was
      obvious--patients with CAD dominated (74%) and the fraction of patients with CAD
      in men's group (83%) was significantly higher than in women's group (50%), p <
      0.05. CONCLUSIONS: No significant difference was revealed in the accuracy of
      myocardial perfusion SPECT in men and women. Our results are in accordance with
      the prevailing opinion in literature that discovered differences in sensitivity,
      specificity and diagnostic accuracy are usually not statistically significant or
      that they can be explained by the selection bias of patients in angiographically
      verified groups (significantly higher fraction of patients with CAD in men's
      group).

PMID- 14600888
TI  - Cerebral blood flow SPECT may be helpful in establishing the diagnosis of
      progressive supranuclear palsy and corticobasal degeneration.
AB  - BACKGROUND: We present 4 cases, which illustrate the usefulness of neuroimaging
      studies in atypical forms of Parkinsonism. Progressive Supranuclear Palsy (PSP)
      and Corticobasal Degeneration (CBD) are rare neurodegenerative progressive
      disorders of the central nervous system of unknown cause. The clinical accuracy
      in this diagnosis is not very high even in centres specialising in movement
      disorders. Functional imaging can be helpful in diagnosing PSP and CBD. MATERIAL
      AND METHODS: We present the results of cerebral blood flow (CBF) SPECT scanning
      in 2 patients with PSP and 2 patients with CBD. This was performed using a triple
      head gammacamera and 99m Tc-HMPAO. RESULTS: In PSP patients a diffuse frontal
      perfusion deficit was seen, eventually with striatal and occipital hypoperfusion.
      CT/MRI was either normal or showed a diffuse cortical-subcortical atrophy. In CBD
      patients left fronto-parieto-temporal cortex and a striatal hypoperfusion were
      shown. CT scanning was normal in one case and showed an asymmetrical temporo
      parietal atrophy in second one. CONCLUSIONS: The pattern of diffuse frontal
      perfusions deficit in PSP and asymmetrical, contralateral to symptoms of CBD,
      cortico-subcortical hypoperfusion may be helpful in establishing the correct
      diagnosis.

PMID- 14600889
TI  - The role of scintimammography and mammography in recurrent breast cancer.
      Evaluation of their accuracy using ROC curves.
AB  - BACKGROUND: With the increasing demand for breast conservation surgery, the
      probability of recurrent tumour within the breast increases. Traditionally x-ray
      mammography (XMM) was used to assess the post-surgical breast, but post-surgery
      and radiotherapy changes have reduced the accuracy of this method.
      Scintimammography (SMM) has also been proposed and appears to be more accurate
      than XMM. MATERIAL AND METHODS: A total of 101 women received (Tc99m) MIBI SMM
      and 88 had a subsequent XMM. There were 142 sites suspected of loco-regional
      recurrence breast cancer. During the study the patients did not receive any
      treatment other then hormonotherapy. SMM was performed by the standard Diggles
      Khalkhali method and XMM was performed using standard 2 views. Analysis was
      performed and the results of each type of imaging compared with histology. In the
      ROC curve analysis 5 points of certainty were used: from 1 being definitely
      normal to 5 being definitely cancer; grades 4 and 5 were counted as positive.
      RESULTS: The overall sensitivity value of SMM was 84% and specificity was 85%,
      compared with a sensitivity of 52% for XMM and a specificity of 84%. Analysis of
      areas under ROC curves provides statistically significant difference between SMM
      and XMM (p < 0.05). Combining the two tests did not significantly improve the
      diagnostic accuracy of sequence imaging over SMM. CONCLUSION: ROC curve analysis
      demonstrates that scintimammography should be the primary investigation in
      suspected local recurrence following breast conservation surgery.

PMID- 14600890
TI  - Hepatic plasma clearance of 99mTc-HEPIDA as a diagnostic tool: theoretical basis
      for a simplified determination.
AB  - The determination of hepatic plasma clearance of( 99m)Tc-HEPI-DA is becoming a
      clinically attractive test. It is not necessary to perform always the
      determination using an extensive sampling of blood over the period of 0-90 min
      post injection of the radiopharmaceutical. For screening purposes a simplified
      method is adequate, even if less precise of the low values of the clearance. In
      this paper a theoretical basis has been presented for the development of such a
      simplified procedure, based on a single plasma sample for determination of the
      hepatic and urinary clearance of (99m)Tc-HEPIDA.

PMID- 14600891
TI  - Pretest clinical diagnosis of coronary artery disease and stress myocardial
      perfusion scintigram.
AB  - BACKGROUND: To assess the probability of perfusion defects at exercise stress
      myocardial perfusion SPECT scintigraphy from pretest clinical diagnosis (medical
      personal history, previous ergometric investigation). To determine the value of
      clinical factors for probability of scintigraphic defects with respect to
      avoiding unnecessary investigation in subjects with low probability of abnormal
      scintigrams. MATERIAL AND METHODS: 2143 subjects (1235 men, 908 women) were
      investigated by SPECT perfusion scintigraphy at stepwise increasing exercise
      stress. They were divided into three groups with regard to their medical history
      and exercise test at scintigraphy: subjects without any signs of coronary artery
      disease (CAD), patients with high likelihood of CAD (i.e., typical anginal pain,
      in particular at stress, positive stress ECG changes, angiographically documented
      important CAD) and patients after myocardial infarction (MI). Important risk
      factors (hypertension, diabetes, age and sex), as well as the role of
      revascularisation procedures, were taken into account for multiple logistic
      regression in order to express their importance for the odds of scintigraphic
      defect visualisation. RESULTS: Perfusion scintigraphic defects (PSD) were found
      in 5.2% of subjects without signs of CAD, in contrast to patients with manifest
      CAD (68.8% with PSD) and in those after MI (90.2% with PSD). There were other
      important factors corroborating the likelihood of PSD (in decreasing order of
      importance): diabetes, male, ECG changes at stress, increasing age. Successful
      revascularisation improved scintigraphic images. CONCLUSION: The examination of
      CAD symptom-free subjects, in particular with atypical chest discomfort, is
      useless. SMPS in patients after documented MI is to be carried out for other
      intended purposes, not for CAD diagnosis only. SMPS is highly recommended in
      patients with CAD symptoms and high CAD probability in order to decide further
      treatment and prognosis.

PMID- 14600892
TI  - Does quantification of myocardial perfusion SPECT study differ while image
      reconstruction is carried out using iteration algorithm instead of filtered back
      projection?--preliminary report.
AB  - BACKGROUND: The purpose of this study was to compare the performance of two
      reconstruction algorithms: conventional filtered back-projection (FBP) and an
      iterative algorithm--ITW--in quantitative analysis of myocardial perfusion SPECT
      studies. The defect size and defect severity were assessed on (99m)Tc-MIBI images
      reconstructed using both methods and estimation of sensitivity in the detection
      of perfusion deficits and myocardial viability were performed as well. METHODS
      AND RESULTS: The study group comprised 43 patients (38 men and 5 women) in the
      age of 40-73 years (mean 59 years). Heart perfusion scintigraphy was performed
      following an injection of 22 to 25 mCi 99mTc-MIBI for exercise and rest
      myocardial perfusion study. Images were reconstructed using FBP and ITW
      algorithms. Defect size (DS) was quantified by a threshold program and CEqual
      programme. Defect severity (nadir) was calculated as the ratio of minimal/maximum
      counts from bull?s eye polar map. Coronary arteriography was performed in all
      patients. RESULTS: Defect size calculated by threshold method on resting images
      did not differ between reconstruction methods (p=0.61 for cut-off 50% and p =
      0.24 for cut-off 60%); defect severity was higher on images reconstructed with
      ITW (CI(0.95) = 2.4%;5.2% of maximal counts). CONCLUSIONS: Sensitivity for
      detection of heart perfusion defects and estimation of myocardial viability were
      similar on images reconstructed by both algorithms.

PMID- 14600893
TI  - Metabolic characterisation of solitary pulmonary nodules by positron emission
      tomography with FDG--preliminary report.
AB  - BACKGROUND: In the past some authors evaluated FDG-PET as a powerful tool for non
      invasive assessment of malignancy of solitary pulmonary nodules (SPN). The aim of
      this paper is to verify the performance of positron emission tomography with
      fludeoxyglucose (FDG-PET) in SPN in the conditions of the Czech Republic during
      the first 16 months of the operation of the PET Centre Prague. MATERIAL AND
      METHODS: The group of 22 patients with 23 SPN was investigated by dedicated PET
      scanner due to inconclusive CT scan. Micromorphological confirmation was
      available in 61%; follow-up (median = 12 months) concerned the other 39% SPN.
      RESULTS: PET was clearly positive in 11 nodules, all were malignant according to
      micromorphological assessment. PET was completely negative in 10 nodules, 3 of
      them were micromorphologically evaluated as benign, the other 7 nodules were
      followed up without any signs of malignancy. In two cases, PET revealed enhanced
      glucose consumption, but the pattern was not typical for malignancy. These cases
      were considered as bronchopneumonia, but till now, they have not been definitely
      resolved. CONCLUSIONS: Excluding two unresolved cases, sensitivity and
      specificity of FDG-PET was 100% for malignancy in our series. PET was helpful in
      medical decision-making in all patients.

PMID- 14600894
TI  - 14C-urea breath test in the detection of Helicobacter pylori infection.
AB  - Helicobacter pylori infection is supposed to be one of the major causes of
      digestive and other diseases. Among a lot of invasive and non-invasive methods
      for its detection, none is ideal. The aim is an assessment of the Helicobacter
      pylori infection in the stomach using breath test and comparison to other
      diagnostic methods, as well as following up the effects of therapy. In 17
      patients with digestive discomfort, breath test, rapid urease test and histology
      were performed, while in 47 patients with proven HP infection the effect of
      therapy was followed up using breath test and clinical findings. Breath test was
      performed after per oral administration of the capsule of (14)C urea (37 kBq).
      Findings of the breath and urease tests were in accordance in 14/17 patients
      (83%) while breath test and histology in 16/17 patients (94%). During follow-up
      of the therapeutic effects, breath test and clinical findings were in accordance
      in 43/47 patients (98%). Breath test can be useful in diagnosis but is a method
      of choice in following up the patients after therapy for H. pylori infection,
      because it is non-invasive, fast and precise.

PMID- 14600895
TI  - Personal dosimetry in the PET Centre Prague.
AB  - This work is focused on radiation protection in the PET Centre Prague. The
      personal year dose equivalents of physicians, technologists and lab-technologists
      in the period 1997-2000 are presented. Dose equivalents are listed for each group
      as collective, mean and maximum dose equivalents and number of people in the
      evaluated group. There is an increase in the dose equivalents in 1999 when the
      PET scanner was installed. Later on, when personnel was trained and better local
      shielding was used, the increase is not much higher even though the number of
      patients investigated per day doubled. The radiation field measurements showed
      that the radiation dose equivalent rate outside the controlled area is on the
      background level of about 0.17-0.18 mSv/hour.

PMID- 14600896
TI  - Are CSF neopterin levels a marker of disease activity in multiple sclerosis?
AB  - The study aimed to evaluate neopterin levels in cerebro-spinal fluid (CSF) as a
      marker of disease activation and progression of multiple sclerosis (MS).
      Neopterin, a substance known to be released from macrophages and monocytes at
      increased rates in cellular immune reactions, was investigated by
      radioimmunoassay, in the CSF of 19 patients with MS during exacerbations of the
      disease, in 34 patients with other neurological diseases (OND) and in 20 normal
      subjects used as controls. Poser's criteria were used for the diagnosis of MS.
      Although elevated neopterin levels in the CSF of patients with MS during
      exacerbations have been reported by other investigators, we found such elevation
      in only 4 out of 19 patients with MS (21%), in 5 out of 34 patients with OND
      (14.7%), and in none of the control group. Student's t-test was used for
      statistical analysis. There was no significant difference in the CSF values of
      the MS patients, the patients with OND (p > 0.05) or the controls. These results
      indicate that neopterin levels in CSF may not be considered a marker of disease
      activity in MS.

PMID- 14600897
TI  - Aortal aneurysm as a cause of ileus.
AB  - A 62-year-old patient presented with flatulence, abdominal distension and other
      symptoms of ileus. Roentgenographic finding found compression on duodenum. Blood
      pool scintigraphy ((99m)Tc erythrocytes) showed aortal aneurysm, while
      simultaneous gastric emptying study with liquid meal ((99m)Tc-S-colloid) showed
      dislocation of duodenum and compression from abdominal aortal aneurysm.

PMID- 14600898
TI  - Introducing the PET Centre Prague.
AB  - The PET Centre Prague (www.homolka.cz/nm) was established in 1999 as the outcome
      of a joint project of the public Na Homolce Hospital and the Nuclear Research
      Institute Rez, plc, the Czech radiopharmaceutical producer. Technical and
      financial assistance was provided by the International Atomic Energy Agency,
      which perceived the Centre as its model project that could serve as a guide for
      the development of PET centres in countries sharing a comparable level of
      development with the Czech Republic. The article maps the history of the project,
      its design, workplace lay-out and equipment, radiation protection arrangements
      and spectrum of the first approx. 3,000 investigations.

PMID- 14600899
TI  - Cerebral blood flow changes in Parkinson?s disease associated with dementia.
AB  - Dementia is one of the main non-motor symptoms of Parkinson's disease (PD) and it
      is diagnosed in about 30% of cases. Its aetiology remains unclear and
      contributing factors are controversial. Dementia may be more common in old
      patients with severe motor symptoms and mild cognitive impairment. Clinico
      pathological studies show the association between dementia in PD and the age
      related group of dementias, such as AD and VaD. A valuable aid in the assessment
      of dementia in PD is cerebral blood flow (CBF) brain SPECT scanning. It shows
      three different patterns of rCBF reduction, including frontal lobe hypoperfusion,
      Alzheimer-like type of hypoperfusion and multiple, vascular defects. The
      heterogeneity of rCBF reduction may reflect the multifactorial pathophysiology of
      dementia in PD. It may result from concomitant AD pathology, cerebrovascular
      disease, destruction of nigro-striato-frontal projection or may be a distinct
      disease of different aetiology.

PMID- 14600900
TI  - Labelled monoclonal antibodies used for the detection of inflammatory processes
      and and bone marrow metastases.
AB  - This review gives a short history of the developments of immunoscintigraphy using
      radiolabelled monoclonal antibodies and will look at some clinical indications
      studied in close cooperation with international groups. Examples are presented of
      infected orthopaedic prostheses and the diagnosis of osteomyelitis in diabetic
      foot in which the method is considered diagnostically helpful. Furthermore, the
      accuracy of the bone marrow immunoscintigraphy is discussed in evaluating results
      of a multi-centre study, clearly demonstrating its diagnostic superiority over
      bone scanning in metastatic cancer. It is concluded that the future diagnostic
      trend is going towards more specific agents (antibodies, peptides) and a speedier
      availability of the diagnostic results in cases of supposed infection.

PMID- 14600901
TI  - XII Congress of the Hungarian Society of Nuclear Medicine.

PMID- 14600904
TI  - Current status and future plans of Nuclear Medicine Procedure Guidelines in
      Central and Eastern European EANM member societies compared with those in other
      EANM member societies.
AB  - The main aim of the EANM Task Group on Quality Assurance and Standardisation is
      to develop harmonised clinical procedures that are accepted within Europe. In
      order to achieve an evidence-based analysis of guidelines this Task Group
      conducted a survey by means of a questionnaire in the 27 EANM member societies in
      July 1999, which investigated the current status of national guidelines in EANM
      member societies, specification of the cover and level of these national
      guidelines, and future desires for national, EANM and SNM guidelines. A
      reanalysis of the data of this survey was undertaken to evaluate the differences
      and similarities between 9 Central and Eastern European (CEE) EANM member
      societies and 18 non-CEE (mainly Western European) EANM member societies with
      regard to the aforementioned investigated topics. The results of this reanalysis
      show only minor differences between CEE and non-CEE EANM member societies with
      regard to the aforementioned topics. Both in CEE and in non-CEE EANM member
      societies, there is limited coverage of existing guidelines, leaving most
      procedures uncovered. Although the infrastructure for guideline development is
      present in both groups, the main explanation for this similarity is the limited
      advancement of the guideline development process, in both the CEE and non-CEE
      EANM member societies. Both groups are willing and ready for guideline
      development at the EANM level, with more concordant than discordant reasons for
      this. This allows a synchronous implementation of procedure guidelines in CEE
      EANM member societies.

PMID- 14600905
TI  - Diagnostic accuracy of mammography and scintimammography in detection of primary
      breast cancer related size of the tumour.
AB  - BACKGROUND: The detection of breast cancer relies on physical examination and
      mammography (XMM). The sensitivity of conventional imaging is lesions-size
      dependent. However, mammography has good sensitivity in small tumours when
      microcalcification is present, but the sensitivity is relatively low in other
      small tumours. The use of scintimammography with Tc-99m sestaMIBI (SMM) may be
      helpful in this situation. The aim of this study is to compare the diagnostic
      accuracy of mammography and scintimammography across all groups with different
      sizes of lesions. METHODS: Data for 273 patients aged 26 to 84 years (mean 52; SD
      12) with 298 lesions were analysed. All lesions were removed and final histology
      and pathological size of the tumours were retrospectively reviewed (mean size 2.9
      cm, SD 2.4 cm). All patients had XMM and SMM. Each imaging study was graded using
      five grades of certainty. SMM images were reviewed by an independent specialist
      blinded to clinical presentation and XMM results. The diagnostic accuracy of each
      test, overall and by each lesions size subgroup, was compared using receiver
      operating characteristic curve (ROC) analysis. RESULTS: The sensitivity of
      scintimammography was consistently high across all size groups; overall 89%
      (82?100%) compared with 68% (51?88%) for mammography. In those tumours below 2
      cm, the area under the ROC was significantly larger with SMM than XMM (p < 0.05),
      with 80% certainty indicative of greater diagnostic accuracy. Also in all
      patients the area under the ROC was significantly larger with SMM than XMM (p <
      0.05), with 90% certainty indicative of greater diagnostic accuracy. In other
      groups of lesions size the area under ROC for SMM was larger in lesions size
      between 2 and 4 cm and slightly smaller in lesions over 4 cm, but it was not
      significant. CONCLUSION: Scintimammography using Tc-99m sestaMIBI seems to be a
      sensitive and consistently reliable diagnostic test for breast cancer independent
      of the size of the tumour.

PMID- 14600906
TI  - Pharmacological radionuclide ventriculography for detection of myocardial
      contractile reserve in patients after myocardial infarction: head-to-head
      comparison of low dose dobutamine and low dose dipyridamole.
AB  - BACKGROUND: Low dose pharmacological stress echocardiography with either
      dobutamine or dipyridamole infusion has been proposed for recognition of
      myocardial viability. However, dependence on adequate acoustic window, observer
      experience, and the mild degree of wall motion changes make the viability
      assessment by stress echocardiography especially bothersome. The objective of the
      study was to evaluate the ability of low dose dobutamine and low dose
      dipyridamole radionuclide ventriculography to detect contractile reserve in
      patients after myocardial infarction and functional recovery after coronary
      angioplasty. METHODS: The study group consisted of 20 consecutive patients (52 +/
      10 years, 17 male, 3 female) with previous myocardial infarction and resting
      regional dyssynergy, in whom diagnostic cardiac catheterization revealed
      significant one-vessel coronary artery stenosis suitable for angioplasty. Each
      patient underwent equilibrium 99m-Tc radionuclide ventriculography which was
      performed at rest and during low dose dipyridamole (0.28 mg/kg over 2 minutes)
      and low dose dobutamine infusion (up to 10 mcg/kg/min). Left ventricular global
      and regional ejection fractions were determined. Increase of regional ejection
      fraction for > 5% (inferoapical and posterolateral regions) or > 10%
      (anteroseptal regions) during low dose dobutamine and dipyridamole in infarcted
      regions, as well as in the followup period, was considered as index of
      contractile reserve. After 8 weeks of successful angioplasty, resting
      radionuclide ventriculography was repeated in all patients in order to identify
      functional recovery of the infarct zone. RESULTS: Out of the 180 analyzed
      segments (20 x 9), 90 regional ejection fractions have shown depressed
      contractility. The mean of the regional ejection fractions showing depressed
      contractility increased from the resting value of 34 +/- 12% to 42 +/- 14% in the
      follow-up period (p = 0.06). Of the 90 with baseline dyssynergy, 46 were
      responders during low-dose dobutamine (51%), whereas 32 segments were responders
      (36%, p = 0.05 vs. dobutamine) during low dose dipyridamole. Positive predictive
      value of dobutamine and dipyridamole for predicting functional recovery was 72%
      and 75% (p = ns), respectively. Negative predictive value of dobutamine and
      dipyridamole was 48% and 69% (p = 0.05), respectively. In the group of patients
      with most severe dyskinesia (regional ejection fraction < 35%, 42 segments)
      positive predictive value was 73% and 82%, while negative predictive value was
      42% and 64% for low dose dobutamine and low dose dipyridamole respectively (p =
      ns). CONCLUSION: Although low dose dobutamine induced higher rate of positive
      responses during radionuclide ventriculography imaging, dipyridamole radionuclide
      ventriculography has shown superior, particularly negative, prognostic value for
      predicting functional recovery of infarcted regions.

PMID- 14600907
TI  - Diagnostic sensitivity of three tumour markers in non-small cell lung cancer: a
      pilot study.
AB  - BACKGROUND: Three tumour markers (CEA, CYFRA 21.1 and CA125) were evaluated for
      diagnostic sensitivity in newly diagnosed, untreated non-small cell lung cancer.
      METHODS: In the 24 patients studied, the tumours were classified histologically
      as 15 squamous cell carcinomas and 9 adenocarcinomas. In 19 cases, the disease
      was confined to the lung (M0); 5 cases presented with metastatic disease at the
      time of diagnosis (M1). RESULTS: CA125 displayed the best overall sensitivity
      (62%) and also when only localised disease was evaluated (63%). CA125 was the
      most sensitive marker for adenocarcinomas (89%), with values differing
      significantly with histological type (p < 0.005). CYFRA 21.1 was most sensitive
      in squamous cell carcinomas (53%); this was the only marker which was elevated in
      all cases involving metastatic disease, and exhibited a significant correlation
      with stage (p<0.02). CEA presented the poorest overall sensitivity (42%). The
      overall sensitivity of the three-tumour marker association was 79% and the best
      combination of two markers was CYFRA 21.1 + CA125 (75%). CONCLUSIONS: This pilot
      study allows recommendation of the associated use of these two markers as first
      choice of diagnostic aid in non-small cell lung cancer. Further measurements,
      including specificity studies in benign lung diseases, should be performed to
      confirm these results.

PMID- 14600908
TI  - Medical radiation exposure of the Czech Republic paediatric population due to
      diagnostic nuclear medicine.
AB  - BACKGROUND: The information on the results of the survey of collective effective
      dose SE to children in the Czech Republic (CR) due to nuclear medicine
      examinations performed during the one-year period July 1995-June 1996. METHODS:
      The estimate of SE was based on the annual frequency of nuclear medicine
      procedures and the type and amount of administered radiopharmaceuticals provided
      by the General Health Insurance Company covering 75% of the CR population.
      RESULTS: In the period considered, 15,281 examinations of children younger than
      18 years were performed, which represented 7.5% of total nuclear medicine
      examinations in the CR. The annual SE 43.8 man Sv formed 5.1% of the collective
      effective dose to all patients examined by nuclear medicine procedures in the CR.
      The contributions of procedures in various body systems of children to the annual
      SE: urinary tract 32.8%, bone 30.4%, brain 12.8 %, cardiovascular 6.4%, GIT 6.0%,
      thyroid 4.4%, lungs 3.0%, other 4.2%. In comparison with a similar survey
      performed in the CR in 1987 (based on a questionnaire) there was an increase in
      SE to children younger than 15 years by a factor of 2.8, mainly due to the
      expansion of kidney and bone investigations. CONCLUSIONS: The mean effective dose
      per exam to children younger than 15 years was 60% of that for adults, which was
      in agreement with the requirement that the radiation burden of children should
      not exceed that of adults. The use of data from the Insurance Company for regular
      conducting of such surveys appeared to be not as cumbersome and time-consuming as
      questionnaire surveys.

PMID- 14600909
TI  - New derivatives of 2-(N-arylmethylideneamine) benzophenone oxime as potential
      radiopharmaceuticals for brain imaging.
AB  - BACKGROUND: The aim of this work was the development of a sufficient method for
      synthesis and radiolabelling with technetium- 99m a new class of compounds as
      potential ligands for brain imaging. METHODS: The synthesis of new ligands with
      the structure of 2-(N-arylmethylideneamine) benzophenone oxime (6-10) based on
      the cyclocondensation of appropriate 2-aminobenzophenone oxime 1-2 with
      respective aldehydes 3-4 or ketone 5 in acidic conditions. During our experiments
      in dependencies from the reaction conditions, compounds with the structure of
      Schiff's bases (6-10) or 3N-oxides 1,2-dihrydroquinazoline derivatives were
      obtained. Labelling of compounds 6 or 7 with technetium- 99m was done by stannous
      chloride reduction according to two methods (in ethyl alcohol or in chloroform)
      following the radiolabelling method of HM-PAO. The complex (99m)Tc-HM-PAO was the
      leading compound in our computational calculations with geometrical optimisation
      of a molecule. Using molecular modelling (semi-empirical method ZINDO) we have
      determined the electrostatic potential for the obtained ligands. Additionally we
      have calculated total energy,binding energy, heat of formation and several 3D
      QSAR parameters for theoretically possible complexes of (99m)Tc with the obtained
      ligands. RESULTS: As a result of our experiments a method of a synthesis of new
      compounds 6 and 7 has been developed. Computational calculations were performed
      using the HyperChem 4.5 program. These calculations confirmed our hypothesis that
      only ligand 7 is able to form a complex with (99m)Tc and this complex possesses
      lipophilic properties. CONCLUSIONS: Complex (99m)Tc-7, due to its lipophilic
      properties, is a potential radiopharmaceutical for the brain imaging.

PMID- 14600910
TI  - Wavelet compression of nuclear medicine images.
AB  - BACKGROUND: The wavelet transform is a new mathematical tool for the analysis of
      signals and images. The powerful lossy compression techniques are built on the
      wavelets. METHODS: The static liver scans (byte mode acquisition, 128 x 128
      matrix size) were studied. Four level wavelet transform was performed for image
      compression by means of biorthogonal filters with linear phase characteristic.
      The SPIHT technique (Set Partition in Hierarchical Trees) was used to code the
      wavelet coefficients.<bR> RESULTS: The compression ratios 90:1, with a good
      quality of decompressed images, were achieved (PSNR > 32). CONCLUSIONS: The
      wavelet compression of scintigrams may be a useful practical tool because of
      substantial disk space saving and the reduction of transmission time. The
      decompression of images does not significantly affect their quality.

PMID- 14600911
TI  - Recombinant human TSH for the treatment of differentiated thyroid cancer
      metastatic to the spine.
AB  - The diagnostic use of recombinant human TSH (rhTSH) in follow- up of
      differentiated thyroid cancer (DTC) is already approved, however its application
      in (131)I therapy is still to be evaluated. We report results obtained in four
      patients with DTC metastatic to central skeleton, in whom 5 courses of rtTSH
      aided 131I therapy were administered.

PMID- 14600912
TI  - Systemic radionuclide therapy with Samarium-153-EDTMP for painful bone
      metastases.
AB  - METHODS: We introduced in 33 patients intravenous systemic administration of
      Samarium-153-EDTMP. Average age of patients was 61 years, range from 29 to 83
      years. Mean application activity was 39 MBq per kg of patient's body weight.
      RESULTS: One month after this administration we observed a significant analgetic
      effect in 37% of patients, partial analgetic effect in 37% and we noticed no
      effect in 26% of patients. Three months after administration we observed a
      significant analgetic effect in 45% of patients, a partial effect in 26% and no
      effect in 29% of patients. The withdrawal of bone pain was joined with an
      improvement of the patient's mobility and with the decrease of the necessary dose
      of anodynes and nonsteroid analgetics.

PMID- 14600913
TI  - Breast carcinoma.

PMID- 14600915
TI  - The role of funcional neuroimaging in contrmporary psychiatry.

PMID- 14600914
TI  - Nuclear medicine in the post-genomic era.
AB  - The underlying precepts by which medicine operates will be changed forever by the
      elucidation of the human genomic sequence. The possibility of using limited forms
      of genetic engineering are present and beset by ethical considerations. However
      the use of genetic material in both aiding diagnosing disease and helping our
      understanding of disease processes is being rapidly diffused into clinical
      medicine. As the only method available for the study of function in vivo, Nuclear
      Medicine is ideally suited to act as a bridge between the work in the
      biotechnology laboratory and the patient. This short review will look at some of
      the issues raised by the this new horizon in medicine and how it will impact on
      our practice

PMID- 14600916
TI  - Clinical experience with outpatient radioiodine therapy in hyperthyroidism.

PMID- 14600917
TI  - Relationship of uptake of 99mTc-MIBI in bone metastases to efficiency of
      strontium-89 therapy in prostate cancer patients.

PMID- 14600918
TI  - 67Ga SPECT in detection of infection and inflammation.

PMID- 14600919
TI  - rCBF SPECT in patients after mild cranio-cerebral trauma.

PMID- 14600920
TI  - 99mTc-glutathione in mammary tumor bearing mice.

PMID- 14600922
TI  - Cerebral blood flow SPECT scanning in cortico-basal degeneration.

PMID- 14600921
TI  - Cholescintigraphy in Dubin-Johnson syndrome.

PMID- 14600923
TI  - Beacon-Stm: Non-uniform attenuation correction for SPECT imaging.

PMID- 14600924
TI  - Radio-peptide therapy.

PMID- 14600925
TI  - Preparation of Holmium-166 Labelled Macroaggregates for radionuclide synovectomy.
AB  - BACKGROUND: Radionuclide synovectomy (radiation synovectomy) is an alternative
      method that cures patients with rheumatoid arthritis diseases without surgery.
      During treatment, the suspension of the (166)Ho-macroaggregates radioactive
      particles ((166)Ho-MA) is administrated via intra-articular injection into the
      target joint to destroy the inflamed synovium. MATERIAL AND METHODS: The isotope
      of (166)Ho (E(beta) max = 1.84 MeV, T((1/2)) = 26.8 hr) was prepared by the
      (165)Ho(n, gamma)(166)Ho reaction in the LWR-15 nuclear reactor (8-10 MW) using
      approximate neutron flux 10(14) cm-2s-1. RESULTS: The particles of Ho
      Macroaggregates with suitable dimension 1-20 microm and the mean diameter of 8.5
      microm were prepared. High in-vitro stability was obtained after incubation of
      neutron-irradiated Ho-Macroaggregates in saline solution (0.9% NaCl). The in-vivo
      stability on rats was verified as well. CONCLUSIONS: High in-vivo and in-vitro
      stability as well as supporting gamma radiation of Ho-166 make the
      Macroaggregates a prospective agent for radionuclide synovectomy. The method of
      preparation is relatively easy and allows for the production of particles of a
      suitable dimension with a sufficient amount of radioactivity of Ho-166 for the
      treatment of the rheumatoid arthritis.

PMID- 14600926
TI  - Nuclear imaging techniques in the assessment of myocardial perfusion and function
      after CABG: does it correlate with CK-MB elevation?
AB  - BACKGROUND: An increase of the creatine kinase MB (CK-MB) isoenzyme after cardiac
      surgery suggests perioperative myocardial infarction. The interpretation is more
      difficult when increased enzymes are not accompanied by electrocardiographic
      markers of infarction. The aim of this study was to correlate the results of
      myocardial perfusion imaging (MPI) and radionuclide ventriculography (RNV) with
      CK-MB isoenzyme level in patients without ECG abnormalities after CABG. MATERIAL
      AND METHODS: 36 patients (age: 52.5 +/- 8.5 years, 33M/3F) treated with CABG were
      prospectively studied. CK-MB level was assessed at 0, 4, 8, 12, 24, 36, 48 and 72
      hours after surgery. MPI (SPECT using Tc-99m-MIBI) and RNV were performed 2 weeks
      before and 3-4 months after surgery. All patients had an uneventful
      hospitalisation. The subjects were divided into two groups: group 1 with CK-MB
      increase > 50 IU/ml (n = 9) and group 2 with CK-MB levels </= 50 IU/ml (n = 27).
      There was no difference between the groups regarding the number of diseased
      arteries, haemodynamic parameters, aortic clamping time or the number of grafts.
      RESULTS: Perfusion improvement at stress and at rest was significantly lower in
      group 1 than in group 2. The ejection fraction did not change significantly in
      both groups (DeltaEF = 0.6 +/- 13.5 in group 1 v. 0.7 +/- 9.7 in group 2, p =
      NS), however, in 5 patients from group 1 (56%) and in 6 patients from group 2
      (22%) the EF decreased significantly at follow-up RNV (p = 0.05). In 6 patients
      (5 in group 1 and 1 in group 2) a new defect of perfusion was found at follow-up
      MPI. The sensitivity and specificity of increased CK-MB level in predicting
      perfusion deterioration were 83% and 87%, respectively. CONCLUSIONS: We conclude
      that patients with an increased level of CK-MB isoenzyme (> 50 IU/ml) after
      coronary artery surgery have a higher rate of perfusion and function
      deterioration. The increase of CK-MB level early after coronary bypass surgery in
      patients without ECG markers of perioperative infarction indicates a probable
      ischaemic insult during surgery.

PMID- 14600927
TI  - The comparison of two gated SPET protocols: adenosine Tc-99m tetrofosmin and
      treadmill exercise Tc-99m MIBI.
AB  - BACKGROUND: The effect of adenosine and exercise on gated SPET left ventricular
      ejection fraction (LVEF), end diastolic volume (EDV) and end systolic volume
      (ESV) has not been fully investigated. The aim of the study was to compare
      functional measurements obtained in one-day adenosine rest and two-day stress
      rest protocols in relation to ischaemia. MATERIAL AND METHODS: Out of 226
      consecutive patients examined with submaximal treadmill stress-rest 700 MBq Tc
      99m MIBI, 26 were chosen to match those subjected to adenosine (140 micro
      g/kg/min) enhanced by a low level exercise protocol (300 MBq and 700 MBq Tc-99m
      tetrofosmin for stress and rest respectively). All images were acquired on a
      double head system and were gated using 8 frames, 25 s per frame. RESULTS: ED and
      ES volumes increased after adenosine but decreased after treadmill resulting in
      the post-stress LVEF being significantly greater than after adenosine, 60 +/- 11
      v. 51 +/- 13% (p < 0.01). This was caused by the smaller post-stress ESV in the
      treadmill group 40 +/- 20 v. 51 +/- 34, p < 0.05. In non-ischaemic scans the LVEF
      was greater (61 +/- 8 v. 51 +/- 14, p < 0.01) and EDV and ESV smaller after both
      stress and rest. CONCLUSIONS: The adenosine test may have an opposite influence
      on the EDV and ESV in comparison to the submaximal treadmill test and therefore
      the left ventricular function measurements after adenosine infusion should be
      interpreted carefully and may not represent those acquired after physical
      exercise. In the gated SPET scans showing ischaemia the post-stress EDV and ESV
      may be greater and the LVEF lower than at rest.

PMID- 14600928
TI  - Scintigraphic and ultrasonographic assessment of the effect of lumbar
      sympathectomy upon chronic arteriosclerotic ischaemia of lower extremities.
AB  - The aim of the study was an evaluation of the effect of onesided lumbar
      sympathectomy in patients with peripheral vascular disease of lower
      extremity(ies), using perfusion scintigraphy with (99)mTc-MIBI and ultrasound
      Doppler blood flow-rate measurements. A secondary aim was a comparison of the
      diagnostic efficacy of the two techniques applied. The study was performed on 30
      patients, studied prior to and early after one-sided lumbar sympathectomy. The
      scintigraphy yielded results indicating a statistically significant increase in
      perfusion of femoral and calf muscles (p < 0.001). Ultrasound investigation
      demonstrated significant (p < 0.001) increase of the maximal blood flow rate in
      the popliteal artery. Scintigraphic perfusion study yielded better agreement with
      the clinical evaluation than the ultrasound Doppler technique (83 v. 47 per cent,
      p < 0.01) and higher sensitivity in demonstration of improved blood supply (88 v.
      36 per cent, p < 0.001).

PMID- 14600929
TI  - 99mTc-HEPIDA hepatic clearance as a diagnostic tool: usefulness of plasma and
      hepatic clearance for assessment of hepatic parenchyma performance.
AB  - Plasma clearance of (99m)Tc-HEPIDA (Cl(Pl)) has been used for two decades for
      assessment of liver function in patients with diseases of this organ. A specific
      determination of (99m)Tc-HEPIDA liver clearance (Cl(Hp)) has been developed that
      provides more direct possibility to evaluate performance of liver parenchyma.
      Both tests have been studied in healthy volunteers of varying age (48
      individuals) and in 83 patients with varying degree of liver damage. The liver
      damage has been evaluated on the basis of 5 biochemical tests (AspAT, ALAT, GGTP,
      bilirubine serum concentration, proteinogram) and a score system used for total
      impairment, which was calculated for each patient. Normal range of Cl(Pl) and
      Cl(Hp) was determined from a study on healthy individuals (volunteers). The
      results seem independent of age, but show sex differences. The following values
      (mean +/- SD) of Cl(Hp) were found in males and females of: (181 +/- 31)
      ml//min/1.73 m(2) and (158 +/- 22) ml/min/1.73m(2), and of Cl(Pl) were (224 +/-
      33) ml/min/1.73 m(2) and (202 +/- 25) ml/min/1.73 m(2) respectively. Accepted
      lower boundaries of both quantities (mean -2SD) are 115 ml/min/1.73 m(2) and 150
      ml/min/1.73 m(2) correspondingly. Negative correlation of individual values of
      both clearances in all patients with individual score of liver damage were highly
      significant and correlation coefficients obtained were higher for Cl(Hp) (r = 
      0.63) than those for Cl(Pl) (r= -0.56). Factorial analysis was performed with the
      intention of seeing which of the studied factors had the highest factor loading
      for parenchyma performance that was assumed as the common factor responsible for
      correlations. The highest value was obtained for hepatic clearance (Cl(Hp)) of
      (99m)Tc-HEPIDA. In conclusion this quantity seems highly promising as a
      clinically useful test for assessment of liver performance, both in screening for
      liver damage and for monitoring of organ conditions during therapy and follow-up
      of patients.

PMID- 14600930
TI  - Simultaneous 13C/14C dual isotope breath test measurement of gastric emptying of
      solid and liquid in normal subjects and patients: comparison with scintigraphy.
AB  - BACKGROUND: To develop a simple method for simultaneous solid and liquid gastric
      emptying assessment using a dual isotope labelled breath test. MATERIAL AND
      METHODS: 13 patients were given 100 g ground beef labelled with 25 MBq (99m)Tc
      sulphur colloid and 74 KBq (14)C octanoic acid, and 150 ml 10% glucose drink
      labelled with 8 MBq (67)Ga citrate and 150 mg (13)C acetate. 10 normal volunteers
      were given the same test meals but labelled with (14)C and (13)C only. Breath was
      collected at baseline and regularly for 4 hours. The (14)CO(2) and (13)CO(2)
      activity was measured with liquid scintillation counting and mass spectroscopy.
      The times to maximum (14)CO(2) and (13)CO(2), were determined. Comparison was
      made between times to maximum (14)CO(2) with scintigraphic retention of (99m)Tc
      at 100 minutes and times to maximum (13)CO(2) with the scintigraphic half
      clearance time of (67)Ga. RESULTS: For the solid meal, the times to maximum
      (14)CO(2) were: 60-120 minutes in the 8 patients with normal gastric emptying of
      (99m)Tc; 75-145 minutes for the 10 healthy volunteers; 75-180 minutes for the
      remaining 5 patients with abnormal gastric emptying of (99m)Tc. There was a weak
      but significant correlation (r = 0.56, p < 0.025) between the time to maximum
      (14)CO(2) and gastric retention of (99m)Tc at 100 minutes. For the liquid meal,
      times to maximum (13)CO(2) were: 20-35 minutes for the 4 with normal gastric
      emptying of (67)Ga; 15-40 minutes for the 10 healthy volunteers; 20-75 minutes
      for the remaining 9 patients with abnormal gastric emptying of (67)Ga. There was
      a strong and significant correlation (r = 0.88, p < 0.005) between times to
      maximum (13)CO(2) and gastric half-clearance time of (67)Ga. CONCLUSIONS: Breath
      tests utilising test meals labelled with *C isotopes are valid alternatives to
      scintigraphic studies using (99m)Tc and (67)Ga for the simultaneous assessment of
      gastric emptying of solids and liquids.

PMID- 14600931
TI  - Prickly pear induces upregulation of liver LDL binding in familial heterozygous
      hypercholesterolemia.
AB  - BACKGROUND: The hypoglycemic effect of prickly pear is well known by native local
      Indian population since a long time. Beside the beneficial effects on lipid
      metabolism, oxidation injury and platelet function has been claimed in
      experimental animals. We recently found an upregulation of apo-B/E receptor.
      MATERIAL AND METHODS: We therefore examined 10 patients with isolated
      heterozygous familial hypercholesterolemia (FH) being enrolled in a dietary run
      in phase of 6 weeks after dietary counselling and a further 6 weeks of prickly
      pear addition. Uptake of autologous (123)I-radiolabeled LDL was determined at
      entry as well as after 6 weeks of daily prickly pear ingestion. RESULTS: We found
      a significant (p < 0.0001) increase in LDL-uptake by the liver (24.5 +/- 4.9 vs.
      31.1 +/- 5.2%) and an enhanced decay in circulating blood. Total (298.0 --> 268.0
      mg/dl; p < 0.0001) and LDL-cholesterol (210.5 --> 176.4 mg/dl; p = 0.0001) were
      significantly affected, while HDL (p = 0.0629) and triglycerides were not.
      CONCLUSIONS: These findings demonstrate a significant upregulation of (123)I-LDL
      binding by prickly pear in FH-patients invivo and indicate that prickly pear
      exerts a significant hypolipidemic action via receptor upregulation.

PMID- 14600932
TI  - Long lasting effect of physical stress on the LVEF.
AB  - BACKGROUND: Animal and clinical studies have shown that exercise can deteriorate
      myocardial contractile function. The aim of this study was to examine whether the
      decrease of LVEF measured with gated SPECT lasts as long as 3 hours after
      exercise. MATERIAL AND METHODS: 46 patients with CAD and a control group
      comprising 10 healthy subjects were studied. All patients underwent myocardial
      perfusion gated SPECT with (99m)Tc-tetrofosmin at rest and during stress. SPECT
      was started 1 hour p.i. at rest and twice - 1 hour and 3 hours after injection at
      stress. LVEF values were calculated by the method of Germano, using QGS software.
      RESULTS: LVEF values measured at all time points were significantly lower in CAD
      patients than in control group. In normals mean LVEF values 1h after rest
      injection were similar to those obtained 1 and 3 hours after stress injection
      (59.0 +/- 4.1 v. 60.0 +/- 5.9 v. 58.0 +/- 4.6 respectively; p > 0.05). One hour
      post exercise a decrease of LVEF was observed in 2 patients and 3 hours after
      injection also in 2 patients. CAD subjects showed slightly lower LVEF values
      determined 1h after stress than 1 hour after rest injection (50.8 +/- 13.6 v.
      49.3 +/- 12.8; p < 0.05). More expressed reduction of LVEF was observed 3 hours
      after stress injection as compared to both rest and stress study (50.8 +/- 13.6
      v. 46.0 +/- 12.2; p < 0.001 and 49.3 +/- 12.8 v. 6.0 +/- 12.2; p < 0.001
      respectively). One hour post exercise, a decrease of LVEF values was observed in
      18 patients and 3 hours after injection in 36 patients out of 46. CONCLUSIONS: In
      the majority of patients with CAD physical stress applied for the purposes of
      myocardial perfusion SPECT study results in an impairment of the LV function. The
      impairment of the LVEF caused by physical stress is observed 1 hour after
      exercise, but it increases markedly in frequency and grows stronger during the
      next 2 hours. Patients with CAD who underwent cardiac examination connected with
      physical stress should remain under observation for several hours after
      termination of exercise.

PMID- 14600933
TI  - The usefulness of CBF brain SPECT in forensic medicine: the civil law code cases.
      A description of four cases.
AB  - BACKGROUND: The aim of this report was to assess the usefulness of cerebral blood
      flow (CBF) scanning utilising the SPECT technique in forensic medicine cases in
      the area of civil law cases. MATERIAL AND METHODS: CBF SPECT scanning was
      performed in four patients utilising (99m)Tc-ECD and a triple-head gammacamera.
      In the analysis both the asymmetry index and cerebellar normalisation were
      applied. Reference values were obtained by studying 30 healthy volunteers.
      RESULTS: In those cases CBF SPECT scanning played an important role in forensic
      argument. It influenced the sentence and the amount of financial compensation.
      CONCLUSIONS: CBF SPECT scanning may provide valuable information in forensic
      medicine argument in civil law cases, but only when taken together with
      psychometric tests and other neuroimaging methods (CT, MRI). The value of CBF
      SPECT scanning alone may be limited in judicial proceedings.

PMID- 14600934
TI  - Undergraduate teaching of nuclear medicine: a comparison between Central &
      Eastern Europe and European Union countries.
AB  - This paper overviews the curricula of nuclear medicine (NM) undergraduate
      training in 34 Central & Eastern European (CEE) and 37 European Union (EU)
      medical faculties. The data show enormous variation in the number of hours
      devoted to nuclear medicine, varying between 1-2 to 40 hours and highly
      differentiated concepts/ideas of nuclear medicine training in particular
      countries. In most EU countries this teaching is integrated with that of
      radiology or clinical modules, also with training in clinical physiology. In many
      CEE countries teaching and testing of NM are independent, although integration
      with other teaching modules is frequent. The paper discusses the differences in
      particular approaches to nuclear medicine teaching.

PMID- 14600935
TI  - Application of rhenium-188 HEDP in bone metastases therapy.
AB  - Radionuclide bone metastases therapy is a major achievement of nuclear medicine.
      Development of less radiotoxic and more effective radiopharmaceuticals is
      therefore a challenge for radiopharmacists and industry. This paper reviews the
      application of rhenium-188 HEDP as a reactor- or generator-produced nuclide for
      bone metastases therapy.

PMID- 14600936
TI  - Nuclear medicine and positron emission tomography imaging in cardiology.

PMID- 14600937
TI  - Introducing the PET Centre Bydgoszcz - Poland.

PMID- 14600939
TI  - Radioiodine-treatment (RIT) of functional thyroidal autonomy.
AB  - Since 1942, therapy with radioiodine (RIT) has gained a major role in the
      treatment of benign thyroid disorders, notably hyperthyroidism caused by Graves'
      disease or toxic multinodular goitre (thyroid autonomy). In iodine deficient
      areas thyroid autonomy accounts for 40-50% of all cases with hyperthyroidism. RIT
      has become a cost-effective first-line procedure in autonomy-patients with latent
      or overt hyperthyroidism, especially in the absence of a large goitre, after
      thyroid surgery and in elderly patients with associated conditions who carry a
      high intra- or perioperative risk. Decisions concerning the definitive treatment
      of thyroid autonomy should take into account previous episodes of
      hyperthyroidism, objective parameters of risk stratification in euthyroid
      patients as well as concomitant diseases and the probability of iodine exposure
      in the future. In Central Europe the majority of investigators prefer to estimate
      the therapeutic activity individually by a radioiodine test. TCTUs (global 99m-Tc
      pertechnetate thyroid uptake under suppression)-based dose concepts have been
      proven to be highly effective in the elimination of autonomy and carry a low (<
      10%) risk of post-radioiodine-therapeutic hypothyroidism. Radioiodine therapy for
      autonomy has been found to be both effective and safe and without major early or
      late side effects. The most frequent complication is hypothyroidism requiring
      lifelong follow-up.

PMID- 14600940
TI  - Lung perfusion scintigraphy in the diagnosis of peripheral pulmonary stenosis in
      patients after repair of Fallot tetralogy.
AB  - BACKGROUND: The frequency of peripheral pulmonary artery stenosis in patients
      after surgical repair of tetralogy of Fallot (TOF) ranges from 20 to 40%. This
      can be either primary or secondary to the surgical intervention. The influence of
      resulting lung perfusion alterations on the life quality of patients is difficult
      to predict. The aim of this study was to compare the utility of the diagnostic
      procedures in this group of patients, with particular focus on lung perfusion
      scintigraphy. MATERIAL AND METHODS: This study comprised 104 patients who
      underwent repair of TOF at ages from 5 months to 25 years. The patients have been
      followed up for from 4.2 to 25 years. On the basis of chest x-ray peripheral
      pulmonary artery stenosis was suspected in 11 patients, in 12 on the basis of
      echocardiography examination. RESULTS: Lung perfusion scintigraphy has been
      performed on 87 patients. The disturbances in lung perfusion (mostly in the left
      lung) were show by means of lung perfusion scintigraphy in 43 (49%) of patients.
      In 27 of them heart catheterisation has been performed. Angiography revealed
      stenosis of the lung artery branch in 15/43 (34.9%) patients with abnormal
      perfusion lung scan and in 4/44 (9%) in patients with normal perfusion lung scan.
      Intervention procedures were carried out on 10 patients. CONCLUSIONS: Lung
      perfusion scintigraphy may prove a valuable, non-invasive screening tool in the
      assessment of patients after TOF repair, although both false-negative and false
      positive results may happen. Therefore, it should play an auxiliary role together
      with other diagnostic modalities.

PMID- 14600941
TI  - Alteration of 99mTc-DMSA biodistribution in glomerulonephritis.
AB  - BACKGROUND: The aim of this study was to assess the relation between (99m)Tc-DMSA
      biodistribution and its reliability as a marker of renal function in patients
      with glomerular kidney diseases. MATERIAL AND METHODS: Sixty-seven patients
      involved in this study were classified into two groups according to (99m)Tc-DTPA
      clearance and serum creatinine values: the 1st group consisted of 42 patients
      without renal failure while the 2nd group included 25 patients with renal
      failure. (99m)Tc-DMSA biodistribution was determined by measuring kidney, blood
      and urine activity at 2 h and 4 h. RESULTS: The results, compared with those of
      23 healthy volunteers, indicated the quantitative alteration of (99m)Tc-DMSA
      distribution in both glomerulonephritis patient groups. In reference to the
      control mean values of 2 h and 4 h, in patients without renal failure, kidney
      activity was found decreased to 52% and 57%, while the blood activity increase of
      37% and 44% was recorded together with the urine activity increase of 38% and
      23%. In patients with renal failure the alterations of renal and blood activity
      were more remarkable, but the urine loss was found to be unchanged. CONCLUSIONS:
      It is suggested that these biodistribution changes originate mainly from tubular
      impairment. However, in glomerulonephritis patients, altered glomerular
      filtration might considerably affect biodistribution of this radiopharmaceutical
      and limits its suitability for precise quantitative estimation of renal function.

PMID- 14600942
TI  - Comparative diagnostic value of the breath test and the urine test with 14C-urea
      in the detection of the Helicobacter pylori infection.
AB  - Among 92 patients with chronic gastritis we conducted a synchronous diagnosis of
      the Helicobacter pylori (H. pylori) infection using a culture and a serological
      test (IFP), in conjunction with breath and urine tests involving (14)C-urea (BTU
      C14 and UTU-C14). The infection was confirmed by isolation in 71 persons (77.2%),
      the presence of specific IgG in the blood serum was found in 75 (81.5%). In
      comparison, the BTU-C14 indicated a group of 77 people (83.7%) as infected, and
      the UTU-C14 a group of 76 (82.6%). In order to determine the diagnostic value
      (sensitivity, specificity and efficiency) of the latter tests, the results were
      compared with those of the culture and of the serological tests. It was found
      that the BTU-C14 test used showed a 100% sensitivity, a 89.5% specificity and a
      97.9% efficiency. The UTU-C14 test showed a 100.0% sensitivity, a 94.4%
      specificity and a 98.9% efficiency in the detection of the H. pylori infection.

PMID- 14600943
TI  - The relationship between gallbladder motility and the presence of enterogastric
      reflux.
AB  - BACKGROUND: The aim of the study was an estimation of the relation between the
      gallbladder (GB) motility function and the presence and quantity of enterogastric
      reflux (EGR). MATERIAL AND METHODS: We investigated 172 patients: 90 with
      physiological GB function (filling and emptying) (FGB), 21 with impaired GB
      function (prolonged filling and ejection fraction < 45%) and 61 with afunctional
      gallbladder (AGB) (without visualisation). The study was performed during 90 min
      (1 f/min) after i.v. application of 185 MBq 99m Tc-dietil IDA. After 30 min, a
      test meal was given while at the end the stomach was marked. According to the
      parameters from time activity curves over the stomach and hepatobiliary system,
      the index of EGR was calculated, while GB filling and ejection fraction were
      estimated from the GB time/activity curve. RESULTS: Most frequently, EGR occurs
      in AGB (47.5%), followed by IGB (43%) and FGB (41%), without significant
      differences (p > 0.05). The significantly (p < 0.05) highest value of EGR was
      obtained in the patients with AGB in comparison to IGB and FGB. EGR values were
      in correlation (r = 0.168, p < 0.05) with the functional status of the GB. In the
      patients with pathological values of EGR (> 10%), significantly higher values (p
      < 0.05) are obtained in AGB than in IGB and FGB. Also, these values were in
      correlation with the functional status of the GB (r = 0.284, p < 0.05).
      CONCLUSIONS: We can conclude that EGR occurs more frequently in the patients with
      afunctional GB in comparison with those with functional and decreased motor
      function. Also, EGR quantity is in correlation with the impairment of the GB
      function.

PMID- 14600944
TI  - Simultaneous radiotherapy and radioimmunotherapy of malignant gliomas with anti
      EGFR antibody labelled with iodine 125. Preliminary results.
AB  - BACKGROUND: In this paper we present the preliminary results of a prospective
      trial of the efficacy of simultaneous radiotherapy and anti-EGFR (125)I
      radioimmunotherapy of malignant gliomas with 2 years' total survival as the end
      point, raising the question whether anti-EGFR (125)I radioimmunotherapy
      influences the disease-free survival in these patients. MATERIAL AND METHODS:
      Patients with anaplastic astrocytoma or primary glioblastoma were previously
      treated by a macroscopically radical neurosurgical approach and randomized either
      to radiotherapy + radioimmunotherapy arm or treated by radiotherapy alone. Seven
      patients were included in the group with radioimmunotherapy, among them five with
      GBM and two with AA, and five patients in the control arm. Patients were
      irradiated to 60 Gy using three-dimensional conformal noncoplanar techniques.
      Anti-EGFR (125)I monoclonal antibody 425 radioimmunotherapy (50 mCi/course) was
      started during 4th week of radiotherapy and was repeated three times in one week
      intervals. RESULTS: Time of follow-up ranges between 2 and 10 months in the anti
      EGFR (125)I radioimmunotherapy arm and 4 and 9 months in the control arm.
      Recurrence was diagnosed in all patients in the EGFR (125)I group with a lethal
      outcome in two of them and in 4 patients in the control group. Median time to
      recurrence was 2 and 5 months respectively. CONCLUSIONS: Taking into account
      early recurrences observed, we propose to continue the studies on the efficacy of
      adjuvant anti-EGFR (125)I radioimmunotherapy in a selected group of patients in
      whom the greatest benefit may be expected on the basis of molecular studies,
      among them EGFR expression investigation.

PMID- 14600945
TI  - The effects of radioiodine therapy on peripheral blood lymphocyte subpopulations
      in patients with Graves' disease. Preliminary report.
AB  - BACKGROUND: Treatment of Graves' disease patients with radioactive iodide
      ((131)I) is becoming the standard therapy in an increasing group of cases but can
      induce alterations in immune response, like increasing levels of thyroid
      autoantibodies, and, in part, exacerbation of ophthalmopathy. The aim of this
      study was to assess the changes in peripheral blood (PB) lymphocyte
      subpopulations after (131)I treatment of patients with Graves' disease. MATERIAL
      AND METHODS: The study was carried out in a group of 30 patients with Graves'
      disease (23 f; 7 m) 49.5 +/- 10.0 years of age, 26 with different subjective
      ocular signs like gritty sensation, increased lacrimation, orbital pain, and
      exophthalmos. PB lymphocyte subsets were analysed by cytofluorometry, serum
      concentration of TSH and fT4 were evaluated before and 6 weeks after radioiodine
      treatment. RESULTS: After (131)I treatment a significant increase in CD3+, CD4+,
      CD3+HLA-DR+ and a decrease in CD19+ percentages of lymphocyte subsets were found
      in comparison with the initial evaluation. No significant changes in percentage
      of CD8+ and NK (CD3-CD16+ CD56+) cells were observed during this study. A
      significant increase in TSH and a slight decrease in fT4 concentration
      concentration took place in the 6th week after (131)I application. The patients
      without subjective improvement of ocular signs during the therapy initially had a
      percentage of CD3+, CD8+ lymphocytes which was significantly lower compared with
      those with regression of ocular signs observed after 131I treatment. CONCLUSIONS:
      The changes in PB lymphocyte subsets caused by (131)I treatment of Graves'
      disease confirm the involvement of acquired cellular immunity after radiation
      damage of the thyroid gland. The decreased initial percentage of CD8+ and CD3+
      lymphocytes could help make a prediction of ocular symptoms persisting after
      radioiodine treatment in some patients with ophthalmopathy.

PMID- 14600946
TI  - E-selectin, L-selectin, ICAM-1 and IL-6 concentrations changes in the serum of
      patients with hyperthyroidism in the early period of radioiodine I-131 therapy.
AB  - BACKGROUND: Among cytokines- interleukins: -6 and -8 (IL-6, IL-8) and E-selectin
      (E-sel.), L-selectin (L-sel.) and intercellular cell adhesion molecule-1 (ICAM-1)
      are the most important links in the initiation of the inflammatory process.
      Taking into account that the inflammatory process is the basic stage of effective
      radioiodine therapy, we tried to compare the behaviour of the initial
      inflammatory factors in the early period of I-131 therapy (RAI) of
      hyperthyroidism. The aim of the study was to estimate the behaviour of IL-6, ICAM
      1, E-selectin and L-selectin concentrations in the serum of patients with
      hyperthyroidism before and during I-131 therapy. MATERIAL AND METHODS: The groups
      of 26 patients with Graves' disease (GD) and 18 patients with toxic nodular
      goiter (TNG), aged 34-77, were studied. Control group (C) consisted of 10 healthy
      volunteers. For estimation of thyroid function serum concentrations of TSH, free
      T4 and free T3 were measured by IRMA or RIA kits (Polatom, Poland). IL-6, ICAM-1,
      E-selectin and L-selectin serum concentrations were determined using ELISA method
      by Bender kits (USA). Blood samples for all estimations were taken 10-12 days
      before and in 6th week after I-131 administration. Treatment dose of radioiodine
      was calculated, basing on modified equation for absorbed dose. RESULTS: Compared
      to control, no statistical differences in the levels of E-selectin (C--44.4 +/-
      11 ng/ml) and L-selectin (C--842 +/- 168.9 ng/ml) were observed before treatment
      in the patients with GD (E-sel.--59.8 +/- 19.6 ng/ml; L-sel.--1288.2 +/- 273.5
      ng/ml) and with TNG (E-sel.--61.5 +/- 18.4 ng/ml, L-sel.--1247.0 +/- 273.5 ng/ml)
      as well as in the 6th week after I-131 administration; values in GD group were: E
      sel.--57.3 +/- 19.5 ng/ml, L-sel.--1142.4 +/- 193.4 ng/ml; in TNG group: E-sel.-
      62.1 +/- 20.6 ng/ml, L-sel.--1113.5 +/- 236.3 ng/ml. In comparison to control
      there was no difference in initial IL-6 levels either in GD or in TNG group, but
      a statistically important decrease was observed in the 6th week after I-131
      administration in GD patients (C--2.07 +/- 0.2 ng/ml v. 1.79 +/- 0.16 ng/ml).
      ICAM-1 serum concentrations before treatment were elevated compared to control
      group (C--190.2 +/- 34.7 ng/ml) in both groups (GD--263.6 +/- 24.6 ng/ml, p <
      0.05; TNG--251.4 +/- 36.1 ng/ml, p < 0.05). In GD patients a statistically
      significant increase of ICAM-1 was observed in the 6th week (301.1 +/- 33.2
      ng/ml, p < 0.05) of RAI whereas in TNG group there was no statistical difference
      compared to initial values (249.7 +/- 42.6 ng/ml, N.S.). CONCLUSION: We conclude
      that ICAM-1 and IL-6 may be important factors in the estimation of the
      inflammatory processes in the thyroid gland during radioiodine therapy,
      especially GD disease. E- and L-selectins seem to be not helpful in the
      monitoring of the thyroid inflammatory changes during the early period of I-131
      therapy.

PMID- 14600947
TI  - Hepatic plasma clearance of 99mTc-HEPIDA as a diagnostic tool: experimentally
      derived equations for a simplified determination.
AB  - Determination of the plasma (Cl(Pl)) and specific hepatic clearance (Cl(Hp)) of
      (99m)Tc-HEPIDA is gaining acceptance as one of the best tests for the assessment
      of liver parenchyma functional capacity. A standard method utilises numerous
      blood samples, collected after injection of the radiopharmaceutical, plus
      collection of the urine if specific hepatic clearance is required. It is not
      always necessary to obtain values of the clearances by means of the laborious
      multi-sample procedure. In the paper there are presented formulas, based on
      experimental data, that form the basis of a simplified method for determination
      of Cl(Pl) and Cl(Hp) using single administration of (99m)Tc-HEPIDA. To arrive at
      the value of Cl(Pl) it is sufficient to withdraw 1 blood sample in the time range
      of 60 to 83 min post administration of the radio-pharmaceutical. If Cl(Hp) is
      required, additional collection of urine over the time from 0 to 88-100 min post
      injection is necessary. The values of Cl(Pl) and Cl(Hp) obtained by the
      simplified procedure are in full accordance with those obtained by the reference
      method utilising a series of blood samples, collected from 5 to 90 min post
      injection. The simplified method is sufficient as a procedure for screening of
      patients for liver parenchymal damage.

PMID- 14600949
TI  - Image overlay using alpha-blending technique.

PMID- 14600948
TI  - Cerebral blood flow SPECT imaging in right hemisphere-damaged patients with
      hemispatial neglect. A pilot study.
AB  - BACKGROUND: Hemispatial neglect is characterised as a failure by a brain-damaged
      patient to attend to contralesional space. It is hypothesised to be a result of
      damage to a network involving the frontal, parietal and cingulated cortices,
      basal ganglia and thalamus. MATERIAL AND METHODS: The aim of this preliminary
      study was to verify this model of neglect in 22 right hemisphere-damaged acute
      stroke patients, using single photon emission-computed tomography (SPECT). The
      presence of a single right-sided vascular brain lesion was confirmed on CT and/or
      MRI. Hemispatial neglect, assessed with a battery of drawings, line bisection and
      line and shape cancellation tests, was observed in 12 cases. RESULTS: Patients
      with neglect (compared with those without neglect) had more extensive
      hypoperfusion in the frontal and parietal cortex, as well as striatum and
      thalamus. Left-sided hypoperfusion in the parietal cortex and the thalamus was
      also significantly associated with neglect on SPECT imaging. Performance in three
      out of five psychological tasks commonly used to detect the presence of
      hemispatial neglect, such as drawing tests and line bisection test, was
      exclusively linked with damage to the parietal cortex of the right hemisphere,
      while the line cancellation test might be attributable to the lesion of the right
      striatum. CONCLUSIONS: These findings support the model attributing hemispatial
      neglect to a unilateral defect in a cortico-striatothalamo-cortical loop. CBF
      SPECT imaging may provide a reliable description of the brain pathology
      associated with hemispatial neglect.

PMID- 14600950
TI  - An introduction to economic analysis in medicine--the basics of methodology and
      chosen terms. Examples of results of evaluation in nuclear medicine.
AB  - This article overviews the basic terms and methodology approaches in economic
      analysis in medicine: cost-benefit analysis, cost-effectiveness analysis, cost
      utility analysis and costminimisation analysis. Particular emphasis is put on
      nuclear medicine economic evaluation, e.g. FDG - PET studies, sestamibi breast
      cancer imaging and radioiodine therapy of hyperthyroidism.

PMID- 14600951
TI  - Problem-based education of nuclear medicine technologists as part of a four-year
      integrated bachelor's degree in diagnostic imaging and radiation therapy in The
      Netherlands: report of a transition.
AB  - This article outlines the significant changes that the education of Nuclear
      Medicine Technologists (NMTs) in the Netherlands has witnessed in the past decade
      and a half. The present education is described in some detail here. The choice
      for the pedagogical model is motivated and some educational activities are
      highlighted. Some facts and figures are shown. At the end the interested reader
      is shown the way to some additional sources of information.

PMID- 14600953
TI  - Young patient with wrist pain.

PMID- 14600954
TI  - European School of Nuclear Medicine--21st Seminar, April 18-19 2002, Prague,
      Czech Republic.

PMID- 14600952
TI  - From teaching to self-training i.e. Problem Based Learning.

PMID- 14600957
TI  - Radionuclide treatment of bone metastases--current concepts and trends.

PMID- 14600955
TI  - The Clinic of Nuclear Medicine Prague Motol introduces itself.

PMID- 14600958
TI  - Normative values of 99mTc-MIBI distribution in myocardium in males and females,
      as a basis for quantitative planar scintigraphic method for detection of coronary
      artery disease in patients of both sexes.
AB  - BACKGROUND: Radionuclide perfusion studies of myocardium are being performed
      using planar and tomographic (SPECT) procedures. The latter method enables better
      detection as well as assessment of localisation and severity of scintigraphically
      visualised perfusion defects. On the other hand, lower cost of planar procedures
      using 99mTc-MIBI as the tracer and their much wider availability in countries of
      Central and Eastern Europe could significantly increase the diagnostic potential
      of nuclear cardiology in this region. The aim of the study was an assessment of
      normal distribution of 99mTc-MIBI in the myocardium and generation of normative
      basis for quantitative planar scintigraphic procedure, aiming at detection of CAD
      in patients of both sexes. MATERIAL AND METHODS: The study was based on 250
      patients. The reference (control) group consisted of 53 individuals (29 men, 24
      women) with the low (< 10%) initial probability of CAD as estimated on basis of
      Diamond's tables. The second group included 197 patients (132 men, 65 women) with
      diagnosed CAD or with substantiated suspicion of its presence. In all patients of
      the latter group coronary angiography was performed and was used as the reference
      method for assessment of diagnostic efficacy of the scintigraphic procedure.
      RESULTS: The original own method of acquired data evaluation was based on
      creation of circumferential profiles of activity and on using the procedure of
      trend-fitting for obtaining average curves and their dispersion around the mean
      values. The mean profile curves were obtained for three projections (anterior,
      LAO 45 degrees and LAO 70 degrees ). These mean curves differed significantly
      between both sexes. In LAO 45 degrees projection the differences affected mostly
      the region of the septum and postero-lateral wall of the left ventricle (LV). In
      LAO 70 degrees projection differences were most pronounced in the antero-septal
      wall of the LV. CONCLUSION: Sensitivity, specificity and accuracy of CAD
      detection using the elaborated method, taking into account inter-sex differences,
      amounted to 86, 87 and 86% respectively in males, and correspondingly 81, 84 and
      83% in females. The differences between corresponding indices for two sexes were
      statistically insignificant. For the whole group of patients the sensitivity,
      specificity and accuracy was 85, 86 and 85%, respectively.

PMID- 14600959
TI  - Attenuation correction stress myocardial SPECT: possibility of reduction in
      number of rest investigation.
AB  - BACKGROUND: Attenuation-corrected (AC) imaging frequently shows normal stress
      myocardial perfusion while non-corrected (NC) imaging shows hypoperfusion. The
      aim of the work was to assess whether it is necessary to continue with resting
      examination in this situation. MATERIAL AND METHODS: 121 consecutive patients had
      positive finding at AC and/or NC sestamibi stress myocardial imaging using E.CAM
      Profile system and resting examination was carried out. AC stress imaging was
      normal while NC imaging showed hypoperfusion in 29 cases. In one case this
      finding was reversed. In this group of 30 patients with AC/NC stress
      discrepancies, resting examination has not revealed any additional information in
      28 cases. RESULTS: In 2 cases NC imaging, in contrast to AC, showed stress
      ischaemia. In one of these 2 cases coronarography was carried out with negative
      result. In the other case patient refused coronarography. CONCLUSIONS: The
      resting examination did not bring any benefits in 29-30 cases out of 30 (96.7 to
      100.0%) patients with AC/NC stress discrepancies. If the results of this study
      are considered accordingly, in our group approximately one fourth of the resting
      examinations (29 to 30 out of 121) could be saved.

PMID- 14600960
TI  - Increased redistribution of 99mTc-MIBI under the action of nitrate administration
      -a good tool for detection of myocardial vitality in patients with severe CAD.
AB  - BACKGROUND: The purpose of the study was to investigate and assess patients with
      severe, coronarographically documented coronary artery disease (CAD), previous
      myocardial infarction and left ventricular dysfunction, using radionuclide method
      for myocardial perfusion scintigraphy with 99mTc-MIBI and nitrate administration
      for detection of viable myocardium. MATERIAL AND METHODS: We investigated 56
      patients (37 male, 19 female, mean age 58 +/- 8 years) with CAD and previous
      myocardial infarction, mean EF 38% +/- 12; divided into 2 groups: Group I--28
      patients, investigated at rest, i.v. injected 370 MBq (99m)Tc-MIBI, scintigraphy
      performed at 30 min and 4th hour; Group II--28 patients, investigated at rest,
      i.v. injected 37 MBq (99m)Tc-MIBI, scintigraphy performed at 30 min, immediately
      after that administration of 20 mg Isosorbitdinitrate per os and delayed
      scintigraphy at 2nd and 4th hour. Myocardial SPECT imaging using Siemens Diacam
      with semiquantitative analysis of acquisition data was performed. RESULTS: The
      results established significant but low tracer redistribution in Gr. I, mean
      redistribution 17.5% +/- 5.6. After nitrate administration (Gr. II) we detected
      increased tracer redistribution, mean 30.4% +/- 7.8. The redistribution is higher
      at the 4th hour, compared to that obtained at 2nd hour after injection.
      Comparison of the results before and after PTCA showed sensitivity and
      specificity 93% and 67% respectively. CONCLUSION: It is concluded that after
      nitrate administration (99m)Tc-MIBI redistribution enhances noticeably and may
      play a feasible role in detection of viable myocardium in patients with severe
      CAD.

PMID- 14600961
TI  - Assessment of myocardial perfusion and viability with stress Tc-99m-MIBI SPECT
      before surgical revascularisation. Correlation with postoperative perfusion
      improvement.
AB  - BACKGROUND: The immediate result of successful revascularisation of the
      myocardium is the improvement of perfusion (and in patients with depressed
      ventricular function, functional recovery is expected as an effect of coronary
      flow improvement). The main goal of the work was to assess the value of
      myocardial stress-rest MIBI perfusion scintigraphy in predicting myocardial
      perfusion state measured early (< 5 months) after CABG. MATERIAL AND METHODS:
      Forty-three patients (39 males, mean age 52 +/- 9 years) with chronic coronary
      artery disease underwent prerevascularisation and postrevascularisation stress
      rest Tc-99m-MIBI SPECT studies. Eighty-one percent of patients had a history of
      myocardial infarction, the number of stenosed main coronary arteries was 2.3 +/-
      0.6 per patient, and the left ventricle ejection fraction was 18-70% (mean 46 +/-
      14%). Preoperative perfusion defects were considered as small, medium or severe
      (depending upon stress uptake deficiency) and as transient or persistent
      (depending upon uptake improvement in rest). Changes in perfusion defects
      (improvement, lack of changes or deterioration) were evaluated very early after
      CABG (mean 31 +/- 12 days) in all patients and additionally about 3 months later
      (mean 119 +/- 17 days after CABG) in 36 patients. RESULTS: In transient perfusion
      defects, the probability of early postoperative perfusion improvement was 80% (in
      small defects: 89%, CI(0,95) = 80-94%) and was significantly higher than in small
      persistent defects (51%) and than in medium-and-severe persistent defects (21%).
      In medium-and-severe persistent defects, the lack of changes in perfusion was
      observed in 76% of defects (in severe defects: 81%, CI(0,95)= 69-91%) and was
      significantly higher than in small persistent defects (37%), than in medium-and
      severe transient defects (17%), and than in small transient defects (4%). The
      probability of later postoperative perfusion improvement was 78% in transient
      perfusion defects (in small defects: 85%, CI(0,95)=74-92%) and was significantly
      higher than in small, medium, and severe persistent defects (28%). In medium-and
      severe persistent defects, the lack of changes in perfusion was observed in 71%
      of defects (in severe defects: 81%, CI(0,95)=66-91%) and was significantly higher
      than in small persistent defects (40%), and than in severe, medium, and small
      transient defects (11%). CONCLUSIONS: 1. The result of preoperative stress-rest
      Tc-99m-MIBI SPECT myocardial perfusion study is an exact predictor of the state
      of perfusion measured early (< 5 months) after CABG; the postoperative regional
      perfusion improvement is most dependent upon reversibility and also upon severity
      of stress defect. 2. In small persistent defects, changes in perfusion are
      different than in other types of defects - so they should not be considered
      together with transient defects (as "viable") or with persistent defects (as
      "nonviable"). 3. Preoperative viability assessment on the basis of Tc-99m-MIBI
      study performed solely in rest is unjustified: at the similar perfusion defect at
      rest, the presence of even minimal inducible ischaemia is associated with
      increased probability of perfusion improvement after CABG.

PMID- 14600962
TI  - Comparison of functional imaging and standard CT in evaluation of disease extent
      in patients with tumours showing neuroendocrine features.
AB  - BACKGROUND: The diagnostic approach that should be used in disseminated
      neuroendocrine tumours (NET) remains a significant clinical problem. A novel
      approach has been the use of 111In Octreotide as functional imaging to find NETs.
      Therefore, the aim of this retrospective study is to report our comparison with
      direct CT as standard anatomical imaging. MATERIAL AND METHODS: A total of 48
      patients (aged 16-79 years; mean age 55, SD 14 years) were imaged using both
      techniques with final histological confirmation of NET. Histology was as follows:
      26 carcinoids; 2 pheochromocytomas; 4 gastrinomas, 1 islet tumour; 2
      paragangliomas, 1 modullary carcinoma of the thyroid, 8 undetermined NET and 4
      other tumours with signs of neuro-ectodermal cancers (2 hepatocellular carcinomas
      (HCC), fibrolamellar HCC and fibrous tumour). All patients had (111)In Octreotide
      and 30 had (123)I mIBG scans followed by spiral CT with contrast enhancement. 26
      patients had single functional scans and 22 had multiple, up to 6 scans. Extent
      of disease as number of lesions was compared between CT and octreotide. RESULTS:
      CT was the best modality in 11 patients, in 6 it was as good as (111)In
      Octreotide. mIBG was the best in 6 patients; in 3 patients mIBG was as good as
      octreotide study. In 22 patients (111)In Octreotide was the most effective
      modality. In one patient there was no advantage with any of the tests. Comparison
      of the number of organs involved indicated that an octreotide study was much more
      effective than CT scanning (Wilcoxon matched pairs test, p < 0.001) and also the
      overall number of lesions detected using (111)In Octreotide was greater than with
      CT (Wilcoxon Matched Pairs test p < 0.01). CONCLUSION: Our results confirm the
      recommendation of the European NET group that functional imaging should be
      performed in patients with suspected NET.

PMID- 14600963
TI  - 99mTc-HEPIDA plasma clearance as a diagnostic tool. Total plasma v. specific
      hepatic clearance.
AB  - BACKGROUND: (99m)Tc-HEPIDA total plasma clearance has been used for assessment of
      hepatic parenchyma damage. However, the radiopharmaceutical used is being partly
      cleared from plasma also by the urinary tract. As the share of the latter route
      in total elimination of the compound is not well known, the aim of the study was
      to investigate the percentage of (99m)Tc-HEPIDA eliminated by the kidneys and by
      the liver. MATERIAL AND METHODS: To this aim total plasma clearance of the
      compound and urinary part were determined by the methods employed here in 117
      patients and in 16 healthy volunteers. The pure hepatic clearance was calculated
      as the difference between total plasma and the urinary clearance of (99m)Tc
      HEPIDA. RESULTS: The urinary clearance in patients amounted from 2.6 to 78% of
      total clearance; in the healthy volunteers the corresponding range was from 8.6
      to 28%. Pronounced spread of the urinary clearance (coefficient of variation =
      35%) and lack of correlation between the urinary and total clearance make it
      necessary to take account of urinary elimination in each patient in whom
      reasonably accurate assessment of hepatic clearance is required. CONCLUSION:
      Further studies on the diagnostic efficacy of pure hepatic clearance and its
      change with age in healthy patients appear necessary.

PMID- 14600964
TI  - 18F-fluorodeoxyglucose accumulation in the heart, brain and skeletal muscle of
      rats; the influence of time after injection, depressed lipid metabolism and
      glucose-insulin.
AB  - BACKGROUND: To study the effect of lipid depressing drugs on (18)FDG myocardial
      concentration. The changes of (18)FDG uptake in myocardium, brain and skeletal
      muscle of rats were compared as influenced by acipimox, tyloxapol and glucose
      with insulin. MATERIAL AND METHODS: 5.55 MBq of (18)FDG were administered to
      Wistar rats. Control rats were killed 15, 30, 45 and 60 minutes following
      intravenous injection and the radioactivity concentration (cpm/g of tissue) in
      relation to injected cpm was determined in a well crystal adjusted to 511 KeV in
      order to check the time of maximal (18)FDG tissue uptake. The radioactivity in
      myocardium, skeletal muscle and brain in intact animals was compared with that of
      rats treated with tyloxapol (tritton WR 1339, 125 mg intravenously immediately
      before (18)FDG injection), acipimox (nicotinic acid derivative, 25 mg by stomach
      cannula 15 minutes before (18)FDG), or glucose with insulin (intravenous
      injection of 0.04 g and 0.04 UI immediately before (18)FDG). The animals were
      killed 45 minutes following (18)FDG injection. RESULTS: Tyloxapol and acipimox
      significantly elevated myocardial (18)FDG concentration (tyloxapol +37% and
      acipimox +48%), but the increase in (18)FDG concentration after glucose and
      insulin was slight and insignificant. The changes in skeletal muscle after lipid
      depressing agents were quite contrasting; the decrease in (18)FDG concentration
      was -74% after tyloxapol and -44% following acipimox administration. The
      accumulation of (18)FDG in brain was not influenced markedly by the drugs used or
      by glucose with insulin. CONCLUSION: The highest (18)FDG uptake in myocardium
      could be achieved by depressing the lipid metabolism and not by administration of
      glucose with insulin only. A marked increase in glucose accumulation in
      myocardium is not possible without previous shift from the utilisation of fatty
      acids. This finding is fully in agreement with present knowledge about energetic
      metabolism of myocardium.

PMID- 14600965
TI  - Brain studies--image co-registration and template creation.
AB  - Image co-registration requires special software, which is usually available for
      Unix workstations. This work presents two programs running under MS Windows, one
      for study co-registration and one for template creation. The co-registration can
      be done by minimising/maximising the count difference, squared difference, shape
      and mutual information. The quality of the fit can be estimated by evaluating the
      contours with different tools. The aligned images can be used for template
      creation. Both programs can be downloaded from http://www.homolka.cz/nm.

PMID- 14600966
TI  - The usefulness of CBF brain SPECT in forensic medicine. A description of four
      cases.
AB  - BACKGROUND: The aim of this study was to show the applications of cerebral blood
      flow SPECT scanning in forensic medicine using four cases: two suspects and two
      victims of crime. MATERIAL AND METHODS: Cerebral blood flow studies were
      performed with the use of (99m)Tc-ECD and a triple head gammacamera. Qualitative
      and quantitative analysis was performed, utilising an asymmetry index for
      unilateral perfusion deficits and a comparison to cerebellar perfusion for
      assessing the regional cerebral perfusion. For assessing the normal values, a
      control group of 30 patients was studied. RESULTS: In these cases CBF SPECT
      scanning proved its usefulness in medico-legal argument and played an important
      role in formulating the final forensic expert's opinion. CONCLUSIONS:
      Radionuclide cerebral blood flow studies may play a role in forensic medicine,
      where this method it is mostly under-utilised at present.

PMID- 14600967
TI  - New challenges in nuclear medicine instrumentation. The clinician's point of
      view.

PMID- 14600969
TI  - WBviewer--a way to see tomographic data on PC.

PMID- 14600968
TI  - Radionuclide assessment of myocardial viability.

PMID- 14600970
TI  - A case from Stanford University. Neuroblastoma with diffuse bone marrow
      involvement.

PMID- 14600972
TI  - rCBF SPECT evaluation of dementia.

PMID- 14600974
TI  - Euthyroid sick syndrome in head injury patients compared with Glasgow Coma and
      Outcome Scales.
AB  - BACKGROUND: Evaluation of the role of euthyroid sick syndrome and pituitary gland
      hormonal changes and the prognosis of patient mortality after severe brain
      injury. METHODS: The research was conducted on 65 patients with isolated severe
      brain injury. Blood samples were obtained as soon as possible after the injury
      and on the 1st, 2nd, 3rd, 5th and 7th day after the injury. Blood concentrations
      of T(3), rT(3), T(4), FT(4), TSH, and PRL were estimated. The patients' state of
      health was evaluated in the sixth hour after the injury, using Glasgow Coma
      Scale, and after 180 days, using the Glasgow Outcome Scale. Multidirectional
      correlation was sought between the concentrations of the estimated hormones and
      the score obtained in the Glasgow Coma Scale and Glasgow Outcome Scale. RESULTS:
      Cluster analysis showed that concentrations of the hormones in the patients who
      died are grouped in different clusters from those in the patients who survived.
      This proves that hormonal patterns are different in these groups. Statistically
      significant lower T(3) concentrations were observed on the 3rd day in comparison
      with the 0 day. Cumulative proportion surviving was lower for the OP group in
      comparison with the NOP group and amounted to 0.57. CONCLUSIONS: In all patients
      covered by the research euthyroid sick syndrome was diagnosed. T(3) concentration
      on the 3rd day after the injury together with the evaluation in Glasgow Coma
      Scale allows for more precise prognosis.

PMID- 14600973
TI  - SPECT brain perfusion findings in mild or moderate traumatic brain injury.
AB  - BACKGROUND: The purpose of this manuscript is to present the findings in the
      largest series of SPECT brain perfusion imaging reported to date for mild or
      moderate traumatic brain injury. PATIENTS AND METHODS: This is a retrospective
      evaluation of 228 SPECT brain perfusion-imaging studies of patients who suffered
      mild or moderate traumatic brain injury with or without loss of consciousness
      (LOC). All patients had no past medical history of previous brain trauma,
      neurological, or psychiatric diseases, HIV, alcohol or drug abuse. The patient
      population included 135 males and 93 females. The ages ranged from 11-88 years
      (mean 40.8). The most common complaints were characteristic of the postconcussion
      syndrome: headaches 139/228 (61%); dizziness 61/228 (27%); and memory problems
      63/228 (28%). LOC status was reported to be positive in 121/228 (53%), negative
      in 41/228 (18%), and unknown for 63/228 (28%). RESULTS: Normal studies accounted
      for 52/228 (23%). For abnormal studies (176/228 or 77%) the findings were as
      follows: basal ganglia hypoperfusion 338 lesions (55.2%); frontal lobe
      hypoperfusion 146 (23.8%); temporal lobes hypoperfusion 80 (13%); parietal lobes
      hypoperfusion 20 (3.7%); insular and or occipital lobes hypoperfusion 28 (4.6%).
      Patients' symptoms correlated with the SPECT brain perfusion findings. The SPECT
      BPI studies in 122/228 (54%) were done early within 3 months of the date of the
      accident, and for the remainder, 106/228 (46%) over 3 months and less than 3
      years from the date of the injury. In early imaging, 382 lesions were detected;
      in 92 patients (average 4.2 lesions per study) imaging after 3 months detected
      230 lesions: in 84 patients (average 2.7 lesions per study). CONCLUSIONS: Basal
      ganglia hypoperfusion is the most common abnormality following mild or moderate
      traumatic brain injury (p = 0.006), and is more common in patients complaining of
      memory problem (p = 0.0005) and dizziness (p = 0.003). Early imaging can detect
      more lesions than delayed imaging (p = 0.0011). SPECT brain perfusion
      abnormalities can occur in the absence of LOC.

PMID- 14600975
TI  - Technetium-99mTc-HMPAO brain SPECT in antiphospholipid syndrome--preliminary
      data.
AB  - BACKGROUND: Antiphospholipid syndrome (APS) is defined as the presence of
      repeated episodes of arterial or venous thrombosis, recurrent spontaneous
      abortions and thrombocytopenia in patients with elevated antiphospholipid
      antibodies. An important feature of APS are cerebrovascular disorders of
      thrombotic origin. The aim of the study was to assess cerebral blood flow changes
      utilising brain SPECT HMPAO scanning. METHODS: Brain SPECT (99m)Tc-HMPAO scanning
      was performed in 20 patients with APS: 12 with systemic lupus erythematosus, 4
      with Sneddon's syndrome, 2 with Sjogren's syndrome, 2 with primary APS. 30
      healthy volunteers served as a control group. RESULTS: 19 studies were abnormal,
      1 normal. Abnormalities consisted of multifocal perfusion deficits and diffuse
      decrease of regional blood flow. The average number of focal perfusion deficits
      was 4.8 +/- 1.7. In 7 patients diffuse hypoperfusion of frontal lobes was seen,
      in 1 patient additionally hypoperfusion of temporal and occipital lobes. There
      was a correlation between the number of focal perfusion deficits and cognitive
      impairment in this group of patients. Correlation between SPECT images and
      clinical data was moderate in cerebellar syndrome and paresis, weak in persistent
      headache and vertigo. CONCLUSIONS: Those results indicate the high utility of CBF
      brain SPECT scanning in antiphospholipid syndrome.

PMID- 14600976
TI  - Myocardial perfusion and left ventricular function in long-term follow-up and
      prognosis of electrostimulation cardiomyoplasty.
AB  - BACKGROUND: Twenty two patients with congestive cardiac failure treated
      surgically by dynamic cardiomyoplasty (CMP) with m. latissimus dorsi were
      examined. Myocardial perfusion was assessed with (199)TlCl scintigraphy combined
      with dipyridamole stress-test. In order to obtain direct evidence of myocardial
      perfusion from muscular flap we also injected a bolus of (99m)Tc into a.
      thoracodorsalis, with simultaneous blood sampling from coronary sinus.
      Haemodynamic parameters were assessed using radionuclide angiography. METHODS: In
      a year of follow-up all the patients were assigned to one of two groups: eleven
      patients demonstrated improvement in clinical status (first group) and in another
      group comprising eleven persons no positive effect or deterioration were obvious
      (second group). The patients of the first group before operation revealed two
      times less persistent defect size than patients of the second group. Analysis of
      integral index of persistent defect revealed more expressive differences between
      groups. Before the surgical treatment the patients with improvement in clinical
      status after cardiomyoplasty demonstrated greater size of reversible defect in
      comparison with patients of the second group. In the second group coronary
      fraction of thallium accumulation was 1.4 times higher in comparison to the first
      group, as the result of myocardial hypertrophy in patients with bad prognosis.
      There were no significant differences between the two groups in Il/m level before
      cardiomyoplasty. Before the surgical treatment the patients with improvement in
      clinical status after cardiomyoplasty demonstrated greater ejection fraction in
      comparison with patients of the second group. RESULTS: Cardiomyoplasty led to a
      decrease in the mean size of reversible defects due to indirect
      revascularisation. This hypothesis was testified to by the fact that in patients
      after cardiomyoplasty nuclide appeared in coronary sinus at 10-12th seconds after
      injection into artery thoracodorsalis through anastomoses between the latissimus
      dorsi muscle and the myocardium. The time of appearance of the second wave of
      rise gamma-counting in blood samples from coronary sinus reflects the repeated
      entry of radiopharmaceutical in myocardium after recirculation.

PMID- 14600978
TI  - Diagnostic value of 99mTc-HM-PAO leukocyte scintigraphy and computer tomography
      in patients with sternal wound infections.
AB  - METHODS: 99mTc-HM-PAO leukocyte scintigraphy (LS) and computer tomography (CT)
      were carried out on 19 patients after cardiac surgery; 10 patients with a high
      clinical probability of an infected sternal wound (group II) and additionally 9
      postoperative patients without clinical symptoms of infection, as a control group
      (group I). LS was carried out with mixed, autologous leukocytes, labelled with
      99mTc-HM-PAO in vitro. CT scans were obtained with the use of intravenous
      contrast material. Findings from the LS of control patients (group I) were as
      follows: a cold area in the view of the sternum, a 'biffed sternum' and a
      diffuse, increased lung uptake of leukocytes. The CT scans of the control group
      showed focal oedema, focal haematoma and moderate sternal abnormalities. The CT
      findings of a well-defined fluid collection in the retrosternal space led to one
      control patient being classified as having a retrosternal abscess. In the group
      II, the LS finding of an increased leukocyte uptake and the CT finding of a
      structural irregularity of the sternum, or of air or fluid collection in the
      retrosternal space, were taken as signs of infection. In 11 of the 13 cases, the
      infection was verified clinically: 9 of these proved positive on LS and 8 on CT.
      LS was positive in cases with either superficial or deep processes. In all cases,
      CT revealed whether the infection was limited to the presternal space or whether
      the sternum and mediastinum were also involved. CONCLUSIONS: LS and CT are
      sensitive methods for the early detection of postoperative sternal wound
      infections. CT is superior for the exact localisation of the process, while
      specific signs of infection can be differentiated from those of uninfected
      sternotomy by the use of LS. A combination of LS and CT is suggested in the
      diagnosis of poststernotomy infection.

PMID- 14600977
TI  - Evaluation of the impact of transmyocardial laser (CO2) revascularisation on
      myocardial perfusion--6-months observations.
AB  - BACKGROUND: Transmyocardial laser revascularisation (TMLR) is a relatively new
      surgical approach to symptomatic coronary artery disease patients otherwise
      inoperable by classical revascularisation methods. Perfusion improvement after
      TMLR is considered as one possible mechanism causing alleviation of symptoms in a
      significant percentage of operated patiens. The goal of this work was to assess
      the history f myocardial perfusion during the first 6 month after sole TMLR
      operation. METHODS: TMLR was performed by using high-power (800 W) CO(2) laser.
      Tc-99m-Sestamibi single photon emission computed tomography (SPECT), both in rest
      and stress, was performed 4 times: before TMLR [SPECT-0], very early (mean: 3
      weeks) after TMLR [SPECT-I], 3 months after TMLR [SPECT-II] and 6 months after
      TMLR [SPECT-III] in every patient. The group consisted of 25 patients, including
      21 patients with previous myocardial infarctions. The patients subjected to the
      operation were those suffering from angina in spite of pharmacological therapy,
      with diffuse changes in the peripheral parts of coronary arteries, with left
      ventricle (LV) ejection fraction not lower than 0.30 and with at least one
      transient or small persistent defect in preoperative SPECT. Perfusion was
      assessed in 13 of 17 segments of the LV (after exclusion of 4 septal segments).
      Only a history of transient or small persistent perfusion defects ('viable'
      segments) detected in SPECT-0 is discussed. RESULTS: In comparison to SPECT-0: in
      SPECT-I perfusion did not change in 52% of segments, improved--in 31%, and
      deteriorated--in 17%: in SPECT-II perfusion did not change in 48% of segments,
      improved--in 34%, and deteriorated--in 18%; in SPECT-III perfusion did not change
      in 52%, improved--in 25%, and deteriorated--in 22% of segments. No significant
      difference in the number of segments with perfusion preservation, improvement or
      deterioration in comparison to SPECT-0 was found in SPECT-I,-II or III. In SPECT
      II in comparison to SPECT-I, no changes in perfusion were found in 66% of
      segments, perfusion improved in 20% and deteriorated in 14%. In SPECT-III in
      comparison to SPECT-II, no changes in perfusion were found in 79% of segments,
      perfusion improved in 5% and deteriorated in 15%. CONCLUSIONS: Our evaluation of
      the history of segments with preoperatively transient or small persistent
      ('viable') defects indicates that during the first 6 months after TMLR: 1)
      perfusion is better than before the operation in about one third of the segments,
      and 20 in some of these segments there are dynamic perfusion changes (improvement
      or deterioration) from one to the next postoperative moment of observation.

PMID- 14600979
TI  - Detection of DCIS using 99mTc-MIBI scintimammography in patients with suspected
      primary breast cancer, comparison with conventional mammography.
AB  - BACKGROUND: Scintimammography using Tc-99m MIBI (SMM) is often used clinically as
      a second line diagnostic test for the detection of breast cancer in cases where
      there is concern about the results of x-ray mammography (XMM) and ultrasound.
      Both of these methods, but particularly XMM, may miss a significant proportion of
      ductal carcinoma in situ (DCIS). MATERIAL AND METHODS: This study was performed
      to determine the possible accuracy of SMM in finding DCIS and comparing this with
      the accuracy of XMM in the same patient. Over a 3 year period 353 patients with
      no previous history of breast cancer were imaged with both XMM and SMM. The
      histology of any suspect area was verified by pathological examination of biopsy
      material. There were 203 malignant breast tumours. RESULTS: In those 203 cancers
      there were 15 pure DCIS cancers. SMM correctly diagnosed 12 of these (sensitivity
      was 80%). XMM diagnosed correctly 8 DCIS (sensitivity 53%) and was equivocal in
      2. Combining of both SMM and XMM provided the best result with all but one DCIS
      identified (sensitivity 93%). CONCLUSIONS: This study shows that the SMM is
      helpful in detecting DCIS in those cases where XMM failed to detect DCIS or was
      equivocal. The combination of the two techniques produces a higher sensitivity
      result than either modality alone.

PMID- 14600980
TI  - Quantitative evidence of thyroid stunning in 131I cancer treatment.
AB  - BACKGROUND: An obvious paradox remains in the diagnosis, treatment and follow-up
      of differentiated thyroid cancer by (131)I. The higher the activity for raising
      diagnostic precision, the greater is the potential reduction in therapeutic
      effects. This is due to a phenomenon called thyroid stunning. MATERIAL AND
      METHODS: (131)I tracer and therapeutic parameters: uptake, effective half-life
      and thyroid remnants mass were compared in two different groups of patients. Pre
      treatment planning of radioiodine (RI) ablation was performed in 30 patients
      after administration of 0,185-74 microBq. The same parameters comparison was
      performed in the second group of four cases. They received two or three single
      fractions of 600-2400 MBq 3-15 days apart (a long-term abandoned regime).
      RESULTS: 1. Comparative data collected by pre-treatment planning and subsequent
      RI administration supported the thesis that low range tracer activity (0,7-74
      microBq) does not cause thyroid stunning. We have registered higher or similar
      uptake in thyroid bed after 1100-3700 microbq in 90% of cases. Only in 10% of
      cases was therapeutic uptake lower than the tracer one. In 18% of patients the
      higher rate of uptake was associated with additional thyroid tissue visualized on
      the post-treatment scan. Half-life reduction only could be interpreted in the
      direction of stunning, but such changes characterizes every RI treatment, if it
      takes more than one administration. Data elucidate why our pre-treatment planning
      failed in one-third of the patients. 2. We have clearly observed thyroid stunning
      after 600-2400 MBq (131)I. In one case only, even after 1200 MBq, stunning did
      not take place. Individual RI kinetics appear highly unpredictable. The author
      advocates avoiding high activity first pre-treatment scan in advanced cases with
      elevated thyroglobuline. It remains an unanswered question what time is necessary
      for stunning to recover.

PMID- 14600981
TI  - Radionuclide voiding pattern in children with unstable bladder.
AB  - BACKGROUND: The purpose of this study was to investigate bladder function
      parameters by means of quantitative radionuclide cystography (QRC) in anxious,
      irritable children with unstable bladder. METHODS: Quantitative radionuclide
      cystography was performed in 18 children aged between 8 and 12 years, without
      evidence of neurologic and nephrologic disorders. Findings were compared with
      those obtained in 10 healthy children aged between 7 and 10 years. The dynamics
      of the bladder emptying were studied after intravenous injection of 37 MBq/10 kg
      b.w. 99mTc-diethylenetriaminepentaacetic acid (DTPA) in the posterior views.
      Images of 90 frames every 2 sec. were stored in the 64 x 64 computer matrix
      during voiding. The patients voided into a container and the volumes were
      measured. RESULTS: The parameters evaluated were: functional bladder capacity
      (ml)--FBC, expected bladder capacity (ml)--EBC, percentage of EBC (%), voided
      urine volume (ml)--VV, residual urine (ml)--RU, voiding time (sec)--VT, average
      flow rate (ml/sec)--AFR and peak flow rate (ml/sec)--PFR. There was a
      statistically significant difference between controls and children with unstable
      bladder in the following parameters: FBC 288 +/- 33 vs. 244 +/- 27 ml (p <
      0.001), % of EBC 99 +/- 6 vs. 82 +/- 6% (p < 0.0001), VV 265 +/- 37 vs. 202 +/-
      35 ml (p < 0.0001), RU 22 +/- 11 vs. 48 +/- 19 ml (p < 0.007), AFR 13 +/- 5
      ml/sec vs. 9 +/- 4 ml/sec. (p < 0.01) and PFR 19 +/- 2 vs. 13 +/- 3 ml/s (p <
      0.0001), respectively. The VT obtained from the control group of 23 +/- 9 s did
      not differ significantly from the value of children with unstable bladder of 28
      +/- 14 s. CONCLUSION: The results show that quantitative radionuclide cystography
      is a simple, noninvasive method, which allows a good separation of patients with
      unstable bladder from the children with normal voiding pattern.

PMID- 14600982
TI  - Dynamic esophageal scintigraphy in patients with achalasia.
AB  - BACKGROUND: Dynamic esophageal scintigraphy has been proven as an efficient
      technique of diagnosis of esophageal dysmotility. METHODS: The authors monitored
      the transit velocity, anti-peristalsis and the retention of radioactivity in the
      esophagus by dynamic esophageal scintigraphy in a group of 50 patients (37
      control patients and 13 patients with achalasia). RESULTS: They found a
      significantly longer period of radioactivity passage via the esophagus compared
      to the control group (p < 0.001%). CONCLUSIONS: We observed the statistically
      significant transit prolongation of radioactivity through the esophagus during
      dynamic esophageal scintigraphy (41.2 seconds) in our group of patients with
      achalasia compared to the control group (7.9 seconds). Anti-peristalsis and even
      the radioactivity retention have occurred statistically more frequently compared
      to the control group.

PMID- 14600983
TI  - Identification of transplanted pancreatic islet cells by radioactive dithizone
      [131I]-histamine conjugate. Preliminary report.
AB  - BACKGROUND: The unique mechanism of dithizone action in the interior of the
      viable pancreatic islet suggests the possible development of a specific
      radiopharmaceutical that may have a potential clinical application in the
      diagnosis of the pancreatic organ allografts or islets rejection. The
      radiodiagnostic properties of the newly developed radioactive analogue of
      dithizone, i.e. Dithizone-[(131)I]-Histamine conjugate have been evaluated in the
      present study. METHODS: The four islet cells transplantation models were chosen
      for this purpose. The most important feature of the Dithizone-[(131)I]-Histamine
      conjugate is its possessed ability of zinc chelation. As was presented in the
      recent study, the conjugate stains pink-reddish the isolated pancreatic islets in
      vitro. Among the studied transplantation models, only the islets grafting under
      testis capsule enabled determination of the pancreatic islets in rats by
      radioactive Dithizone-[(131)I]-Histamine conjugate. The level of the
      radioactivity in the recipient testis (right) was almost two times higher
      compared to the controls (0.24 vs. 0.13% ID/g, respectively). CONCLUSIONS: These
      preliminary data demonstrate the ability of the developed radioactive analogue of
      dithizone for in vivo identification of transplanted pancreatic islets, and
      suggests a potential clinical application of the radiodithizone in the diagnosis
      of the pancreatic islet rejection.

PMID- 14600984
TI  - The use of redox polymers in labelling procedures of proteins and peptides with
      99mTc. I. Properties of redox polymers and technique of labelling.
AB  - BACKGROUND: Using a polymer-analogue reaction, redox polymers with a dextran
      matrix to anchor the end alpha(beta)-alanine-N,N'-diacetate group converted into
      the Sn(2+) cycle have been developed for the labelling of proteins, peptides, and
      labile compounds with (99m)Tc. The reaction kinetics and the labelling efficiency
      of (99m)Tc depend primarily on the degree of dextran matrix cross-linking and the
      qualitative nature of the redox polymer end groups. METHODS: Preparation for
      labelling takes place directly in basic protein and peptide solutions without
      adjusting pH or adding other adjuvants. Prior to the final modification into kit
      form, the redox polymers are removed by ultrafiltration. RESULTS: The results of
      labelling of model compounds (aspartic acid, cysteine) with (99m)Tc at various
      solution pH values clearly show that, at pH values over 6.0, it will be primarily
      the free end SH groups that will serve as binding sites for the proteins and
      peptides. To label proteins and peptides, we selected a redox polymer with G-25
      cross-linking, which allows the achievement of a radiochemical purity over 95%
      and high stability of the labelled compounds. CONCLUSION: The method of
      radiolabelling compounds with (99m)Tc based on redox polymers was developed
      mainly to overcome the problems faced when using other conventional methods in
      the labelling of sensitive compounds.

PMID- 14600985
TI  - The use of redox polymers in labelling procedures of proteins and peptides with
      99mTc. II. Technique of preparation of kits for protein labelling by 99mTc and
      its effect on the stability and radiochemical purity.
AB  - BACKGROUND: Our research into new methods of labelling biologically active
      substances with technetium ((99m)Tc) to be used in nuclear medicine is focused on
      proteins and peptides whose labelling is difficult and continues to pose a
      problem. Use of redox polymers is the most gentle of methods as there is no need
      to use other compounds to modify reaction conditions, as is the way with the
      currently employed methods. METHODS: Kits containing proteins, e.g., human
      immunoglobulin (IgG), human leukocytes dialysate (HLD), were labelled with
      (99m)Tc using a redox polymer (RP-IDA) and/or using reduction of pertechnetate
      ((99m)Tc) with stannous chloride. The radiochemical purity was evaluated using
      paper and/or electrophoresis of the labelled proteins. The results were confirmed
      by column chromatography of the labelled IgG. RESULTS: Use of a redox polymer for
      labelling raises the stability of (99m)Tc labelled proteins so that labelling
      efficiency remains virtually the same (96-98%) after 30 hours while it is about
      45% with the routine method using stannous chloride. The stability of protein
      containing kits prepared using redox polymers was improved; the labelling
      efficiency of HLD and IgG after 300 days of kit storage was over 97% and 87%,
      respectively. CONCLUSIONS: The labelling procedure using redox polymers can be
      used in formulating protein- and peptide-based radiopharmaceuticals to improve
      their stability and (99m)Tc labelling efficiency.

PMID- 14600986
TI  - Use of lung and brain perfusion imaging in the HELLP syndrome.
AB  - Patients with multi-organ disorders may present with a plethora of confusing
      symptoms and signs. Often early diagnosis of significant disease is essential and
      can be difficult with standard radiological techniques. This case report presents
      the use of two radioisotopic techniques to assess brain and lung perfusion in a
      patient with such an acute-multi-organ disorder-the HELLP syndrome.

PMID- 14600987
TI  - The role of sentinel node biopsy in breast cancer management: an overview.
AB  - Regional lymph nodes surgical management is an integral part of breast cancer
      therapy. One of the most important therapeutic problems is the risk of surgical
      treatment which is too wide or inadequate due to the lack of correct presurgical
      information on the conditions of regional lymph nodes. For melanoma the problem
      was solved combining surgical accuracy with the slightest surgical resection,
      using sentinel node biopsy. In breast cancer the removal of axillary nodes proved
      to be unnecessary in more than 50% of cases. The first international studies on
      the use of sentinel node biopsy in breast carcinoma for the identification of
      patients who do not need axillary clearance suggest the high accuracy of the
      technique. Some practical problems still exist, however, and the optimisation of
      the method is not yet complete. The use of sentinel node biopsy in breast cancer
      treatment might be able to provide distinctive clinical information, which can
      improve our knowledge about the disease?'s biological behaviour and about its
      treatment.

PMID- 14600988
TI  - Recombinant human TSH in the diagnosis and treatment.

PMID- 14600989
TI  - The attempts to harmonise nuclear medicine in Ukraine.

PMID- 14600992
TI  - Nuclear medicine in Central and Eastern Europe.

PMID- 14600993
TI  - Quantification of breast cancer blood flow in absolute units using Gjedde-Rutland
      Patlak analysis of 99mTc-MIBI uptake.
AB  - BACKGROUND: Scintimammography with 99mTc-MIBI has been proven as efficient
      technique of diagnosis of breast cancer. Nevertheless, quantification of breast
      carcinoma blood flow (BCBF) in absolute units is not yet developed. To compensate
      this, we analysed kinetics of 99mTc-MIBI uptake in breast cancer using Gjedde
      Rutland-Patlak (GRP) approach. METHODS: If BC is radioactivity in breast cancer
      quantified by dynamic scintigraphy, C(h)-blood concentration of 99mTc-MIBI and K
      transport constant, then, assuming 99mTc-MIBI uptake to breast carcinoma
      unidirectional for early minutes after injection and subjected to equation
      d(BC)/dt = K; C(h), classic GRP plot can be obtained from this by integration as
      BC/C(h)=K x (integral of C(h)(dt))/C(h) + V0 and placing [(integral of
      C(h)(dt))/C(h)] as X, and (A/Ch) as Y. The K can be then obtained as slope. K is
      breast cancer clearance equal to product (retention fraction); (blood flow) : K =
      E; BCBF. K can be calculated from A(t) and Ch(t) as asymptote of 99mTc-MIBI
      retention function h(t) = F-1[F[A(t)]/F[Ch(t)]], where F depicts Fourier
      transforms. The BCBF can be then obtained as ratio K/E. We employed the technique
      in 33 patients with breast carcinoma of stages T(1-3)N(0-3)M(0-1) injecting 99mTc
      MIBI (370-510 MBq) as i.v. bolus. In 12 scintigraphy with 99mTc-MAA (370 MBq)
      injected via catheter intraaortically was performed as validation study. RESULTS:
      E values were essentially uniform over the population with overall mean 0.58 sd
      0.06. Blood clearance curves did not differ between various stages also and were
      subjected to biexponential approximation. K was in all cases obtained from the
      slope of initial 3 min part of GRP plot, strongly linear (r > 0.95, p < 0.001) in
      all cases. 99mTc-MAA validation study revealed significant correlation with 99mTc
      MIBI blood flow values (r = 0.94, p < 0.01). The BCBF(as ml/min/100 cm3) was in
      T1 12.85 sd. 4.76, in T2 15.87 sd. 1.78, in T3 17.35 sd. 2.45, and in T4 23.07
      sd. 2.21, expressing tendency to increase with stage. Higher BCBF was
      significantly associated with metastatic spread and in patients with BCBF over 17
      ml/min/100 cm3 distant mets were revealed in all cases. CONCLUSION: Hence,
      analysis of early kinetics of 99mTc-MIBI in breast carcinoma provides correct
      estimates of blood flow in the neoplasm and can be applied in clinical studies
      and for calculation of cytostatic delivery to BC.

PMID- 14600994
TI  - Diagnostic efficacy of optimised evaluation of planar MIBI myocardium perfusion
      scintigraphy: a probabilistic approach.
AB  - BACKGROUND: The Bayesian (probabilistic) approach to the results of a diagnostic
      test appears to be more informative than an interpretation of results in binary
      terms (having disease or not). The aim of our study was the analysis of the
      effect of an optimised evaluation of myocardium perfusion scintigrams on the
      probability of CAD in individual patients. METHODS: 197 patients (132 males and
      65 females) suspected of CAD, with no history of myocardial infarction were
      examined. Scintigraphic images were evaluated applying two methods of analysis:
      visual (semiquantitative) and quantitative, and the combination of both. The
      sensitivity and specificity of both methods (and their combination) in the
      detection of CAD were determined and optimal methods of scintigram evaluation,
      separately for males and females, were selected. All patients were subjected to
      coronary angiography. The pre-test probability of CAD was assessed according to
      Diamond and the post-test probability was evaluated in accordance with Bayes's
      theorem. Patients were divided, according to a pre-test probability of CAD, into
      3 groups: with low, medium and high probability of the disease. The same
      subdivision was made in relation to post-test probability of CAD. The numbers of
      patients in respective subgroups, before and after the test, were compared.
      Moreover, in order to test the reliability of post-test probability, its values
      were compared with real percentages of CAD occurrence among the patients under
      study, as demonstrated by the angiography. RESULTS: The combination of visual and
      quantitative methods was accepted as the optimal method of male scintigram
      evaluation (with sensitivity and specificity equalling 95% and 82%, respectively)
      and a sole quantitative analysis as the optimal method of female scintigram
      evaluation (sensitivity and specificity amounted to 81% and 84%, respectively).
      In the subgroup of males the percentage of individuals with medium pre-test CAD
      probability equalled 52 and after the scintigraphic study it decreased to 21 (p <
      0.0001). In the subgroup of females it changed from 60 to 43 (p = 0.05). The
      verification of the values of post-test probability revealed its high concordance
      with the real frequencies of CAD, with correlation coefficient being 0.98 and the
      regression line differing only slightly from the line of identity. CONCLUSIONS:
      The results confirm the high reliability of the values of post-scintigraphic
      probability of CAD obtained in this way, and support the Bayesian, probabilistic
      interpretation of the study outcome and its application in the diagnostic
      process.

PMID- 14600995
TI  - Evaluation of hemodynamic effects of extracranial carotid stenoses by adenosine
      induced vasodilatation in combination with 99mTc-HMPAO SPECT.
AB  - METHODS: Adenosine was evaluated in combination with 99mTc-HMPAO SPECT as an
      intravenous agent for the pharmacological stress-test of the regional cerebral
      blood flow (rCBF) in 12 patients with internal carotid artery (ICA) stenosis
      without neurologic deficit (8 subjects) or with minimal deficit (4 subjects).
      Also, the adenosine-induced effects on rCBF were correlated with the anatomic
      severity of ICA stenosis. Six normal age-matched volunteers served as control.
      RESULTS: The rest 99mTc-HMPAO SPECT data did not reveal any significant
      interhemispheric asymmetry of perfusion either in ICA stenosis patients or in
      control subjects. No interhemispheric asymmetry was observed in control subjects
      during adenosine infusion either. In ICA stenosis the adenosine test did induce
      interhemispheric asymmetry of perfusion, which ranged between 0.73 and 0.96 when
      quantified as an interhemispheric ratio of 99mTc-HMPAO uptake. In 5 of the 12
      patients with ICA stenosis, adenosine also elicited a short-term muscular
      weakness and/or skin paresthesia consistent with cerebral location of the related
      cortical zones in the stenosis-dependent hemisphere. No correlation was noted
      between the interhemispheric anatomic planimetric asymmetry of stenosis (as ratio
      of patent ICA vessel lumen areas) and perfusion asymmetry at rest. The
      planimetric asymmetry of stenosis correlated significantly with the adenosine
      induced asymmetry of rCBF in ICA-dependent areas (r = 0.78, p < 0.02). The
      correlation could be observed beginning from the magnitude of 70-75% relatively
      to the cross-sectional area of the contralateral intact vessel, equivalent to 45
      50% decrease in the arterial diameter as compared to the intact artery.
      CONCLUSION: Therefore, the conclusion can be drawn that adenosine as a potent
      cerebral vasodilatator may be employed as a challenging agent for functional
      tests of rCBF and that the adenosine test facilitates detection of the
      hemodynamic effects of "minor" stenoses.

PMID- 14600996
TI  - Pharmacokinetic characteristics of 99mTc-Ethylene-l-dicysteine (99mTc-EC).
AB  - BACKGROUND: Ethylenedicysteine-99mTc (99mTc-EC) has been more and more commonly
      applied in dynamic studies as well as for clearance determinations. However, it
      was necessary to investigate in detail the pharmacokinetic characteristics of the
      radiopharmaceutical which may be important for its applicability in assessment of
      renal function. RESULTS: Kidney images obtained from renoscintigraphy are
      characterised by excellent quality without visualisation of the organs adjacent
      to kidneys (liver, spleen). Renoscintigraphic curves demonstrate typical shapes
      with TMAX and T1/2 values not differing from the corresponding values obtained
      for other radiopharmaceuticals (99mTc-MAG3, 131I-OIH). In plasma, 99mTc-EC binds
      with proteins to a considerably lesser degree (c. 1/3) than 131I-OIH (c. 2/3), or
      99mTc-MAG3 (> 9/10). No binding of 99mTc-EC with erythrocytes has been
      demonstrated, whereas 131I-OIH attaches to or penetrates the red blood cells (10
      12%). 99mTc-EC is quickly excreted from the organism: 40 min after i.v. injection
      up to 70% of the administered radiopharmaceutical is found in urine, and at 1 and
      1.5 h after the administration 80% and 95%, respectively. The distribution of
      99mTc-EC in the organism can be described in a fully satisfactory way by means of
      an open two-compartment model, which allows this model to be used for clearance
      determinations. Comparison of the values of renal plasma clearance without
      collection of urine with the values determined by means of measurement of
      activity excreted with urine and mean blood concentration over a finite time
      interval leads to the conclusion that extrarenal plasma clearance of this
      compound (via the liver?) is negligible and amounts to c. 17 ml/min (5-6% of the
      total). The obtained correlation between clearance values for 99mTc-EC and 131I
      OIH supports the contention that extrarenal excretion rate of 99mTc-EC (through
      the liver and bile ducts) is lower than the corresponding rates of either 131I
      OIH or 99mTc-MAG3. A very close correlation between clearance values for 99mTc-EC
      and ERPF (131I-OIH clearance) and between their extraction constants (r = 0.91
      and 0.92, respectively), allows for the introduction of 99mTc-EC to the
      assessment of renal function instead of 131I-OIH. Effective dose to the patient
      from unit activity of 99mTc-EC is comparable with that resulting from
      administration of other radiopharmaceuticals labelled with 99mTc.

PMID- 14600997
TI  - Interobserver variability in 99mTc-DMSA renal scintigraphy reports: multicentric
      study.
AB  - BACKGROUND: The aim of the study was to evaluate the interobserver variability
      and reproducibility of the renal scintigraphy reports. METHODS: The study was
      prospective performed in 60 99mTc DMSA scintigraphies (116 kidneys), done in one
      centre, displayed on X ray films as analogue 300 kcounts images in 4 standard
      projections. Six observers from 4 different centres (group A), including three
      observers from one institution (group B), were asked to interpret original scans.
      Seven parameters of scintigraphy protocol were analysed with at least two
      responses: kidney size (1), uptake (2), outlines (3), scars (4), SOL (5),
      differential function (6) and conclusion (7). RESULTS: Among 116 kidneys,
      concordant results in interpretation of seven points of report from 1 to 7, in
      the group A were found in 62%, 42.5%, 45%, 9%, 47%, 52% and 34%, and In the group
      B in 72%, 55%, 59%, 22%, 62%, 60% and 41% respectively. Some improvement in
      concordant reporting was noted in the group of 3 observers, in comparison of
      group of all, statistically significant in category of scar reports (p < 0.01).
      CONCLUSIONS: Results suggest to use of standardised criteria and terminology in
      interpretations, to improve low interobserver reproducibility and objectivity of
      renal scintigraphy reports, particularly in evaluation of renal scars.

PMID- 14600998
TI  - HIDA-99mTc scanning in demonstrating bile leak after laparoscopic cholecystectomy
      -an unusual pattern of peritoneal bile distribution.

PMID- 14600999
TI  - Scintimammography: a review.
AB  - Scintimammography with 99mTc-MIBI is a new technique which has expanded the use
      of nuclear medicine to a new group of patients in whom scintigraphy was not been
      widely used. When performed correctly, and in those patients, such as the young,
      where x-ray mammography is often non-diagnostic, the sensitivity of
      scintimammography can exceed that of x-ray mammography with a similar
      specificity. A combination of the two techniques in this patient group can
      provide sensitivities greater than 98%. The mechanism of uptake of 99mTc-MIBI in
      breast tissue is better understood as is the efflux of the pharmaceutical from
      the tumour cell. The relationship between the efflux rate of 99mTc-MIBI and the
      expression of the multi-drug resistance gene may help in determining important
      aspects of tumour function, such as the response to cytotoxic chemotherapy. More
      recently the role of scintimammography has been found in those patients with
      suspected breast cancer recurrence where methods depending on the anatomical
      structure of the breast, such as mammography and MRI, are of less use.
      Scintimammography, when correctly performed and correctly applied, is able to
      deliver unique information which is of use to the patient with suspected primary
      or recurrent breast cancer.

PMID- 14601000
TI  - Nuclear medicine in diagnosis and therapy of bone and joint diseases.
AB  - Concerning bone and joint diseases therapy of rheumatic synovitis (=
      radiosynoviorthesis) was introduced in 1952 before clinically relevant diagnostic
      procedures were developed. Radionuclides of Sr and later on 99mTc phosphonates
      then started the wide use of bone scintigraphy since > 30 years. The diagnostic
      methods have an excellent sensitivity for detection of local abnormalities of
      bone metabolism, the specificity of such studies, however, is low. Modifications
      of the technique (3-phase-bone-scintigraphy, pinhole collimators, ROI-technique),
      increasing knowledge of pathological scan patterns and introduction of other
      radionuclide studies (67Ga, 201Tl, inflammation scans with 99mTc-leukocytes or
      99mTc-HIG) as well as 18FDG-PET have increased the specificity significantly in
      recent years and improvements of imaging systems (SPECT) also increased the
      accuracy of diagnostic methods in diseases of bone and joints. Therapy of such
      diseases has made considerable progress: inflamed, swollen joints can effectively
      be treated with 90Y-, 186Re, 169Er-colloids or with 165Dy-particles by
      radiosynoviorthesis. Severe pain due to disseminated bone metastases of cancer or
      polyarthritis can be controlled by radionuclide therapy with 89Sr, 153Sm-EDTMP,
      186Re- or 188Re-HEDP and possibly 117mSn-DTPA with an acceptable risk of
      myelodepression. Possibilities, technical details and limitations of radionuclide
      applications for diagnostic and therapeutic purposes must be considered if
      optimal benefit for individual patients should be achieved. Overall Nuclear
      Medicine can become an essential element in management of bone and joint
      diseases. The relationship of Nuclear Medicine to bone and joint pathology is
      peculiar: In 1952 treatment of rheumatic synovitis by radiosynoviorthesis with
      198Au Colloid was started by Fellinger and Schmid before diagnostic approaches to
      bone pathology existed. Bone scintigraphy was introduced only in 1961 using 85Sr
      but obviously the unfavourable radiation characteristics of this radionuclide
      limited it's broad application and 87mSr did not improve this situation. Only
      when 99mTc phosphonates were developed by Subramanian the importance of bone
      scintigraphy became apparent: The excellent imaging properties of these
      radiotracers showed, that abnormal bone metabolism could be visualized even
      before morphological alterations in the skeleton become visible on radiographies
      or even CT-scans. Moreover, proposals made earlier to use 32P or 89Sr for
      palliation of pain in patients with disseminated skeletal metastases were picked
      up again and led also to other radiopharmaceuticals (186Re-HEDP, 153Sm-EDTMP,
      117mSn-DTPA) which are applied today for the same purpose with very good success.
      Therefore Nuclear Medicine today has a broad program for diagnostic and
      therapeutic approaches to diseases of bone and joints. In bone scanning the high
      sensitivity led to inclusion of this method for routine staging and re-staging
      programs in a variety of cancer forms which have a trend to develop bone
      metastases (e.g. breast, lung, prostate, melanoma) but the low specificity of
      abnormal patterns on such scans can impair the diagnostic value of the technique.
      To increase specificity and to define inflammatory lesions, radiotracers used for
      "inflammation scanning" were introduced such as labeled granulocytes, 99mTc Human
      Immunoglobulin and others but also a simple modification of bone scanning--triple
      phase bone scintigraphy--was used. Recently the excellent properties of 18F for
      PET of the skeleton were rediscovered again and emission CT scanning--possibly
      with overlay with transmission CT or MRT pictures--can enhance the diagnostic
      impact of radionuclide bone studies.

PMID- 14601001
TI  - Evaluation of gallbladder motility in patients following total gastrectomy (Roux
      en-Y) by infusion cholescintigraphy.
AB  - BACKGROUND: The aim of the study is to evaluate gallbladder (GB) motor function,
      by infusion cholescintigraphy, in patients after total gastrectomy (Roux-en-Y)
      with expected disturbances in the physiological regulation of biliary tract
      motility. METHODS: The study was done in 10 controls, as well as in 12 patients
      early (less than 2 months) and in 14 late (6 months-2 years) after surgery.
      Anterior abdominal imaging by gamma camera and computer acquisition was performed
      during three-hours infusion of 150 MBq, preceded by the loading dose of 50 MBq of
      99mTc-EHIDA in bolus injection. The test meal stimulation was done in the 120th
      min of the study. GB TA curve was obtained and five parameters of GB motility
      were analysed: durations of filling (ascending) and emptying (descending) phases,
      filling and emptying rate ratio and ejection fraction and rate. RESULTS: Our
      results have shown that in the early period after the operation GB filling is
      prolonged and emptying impaired, while after several months GB motor function is
      normalised. CONCLUSIONS: It can be concluded that the infusion cholescintigraphy
      is potentially useful in patients after such surgery to decide on the specific
      treatment introduction in order to prevent GB calculosis and other complications.

PMID- 14601002
TI  - SPECT imaging of feet using uniplanar fad-beam collimators.
AB  - BACKGROUND: This study was performed to assess the utility of bone SPECT in the
      feet using a new commercially available uniplanar fan-beam collimator originally
      designed for cardiac imaging. METHODS: 18 patients with symptoms or signs of
      probable skeletal pathology in either the foot or ankle were imaged using a two
      headed gamma camera fitted with uniplanar fan-beam collimators. All patients were
      imaged 2.5-4 h after administration of 500-750 MBq 99mTc MDP. If indicated planar
      dynamic and blood pool images were also obtained. The SPECT acquisition was
      performed in a 128 x 128 matrix, giving a pixel size of 2.00-2.30 mm depending on
      the radius of orbit. Images were displayed as transaxial, coronal and sagittal
      slices and a three dimensional volume rendered image and displayed for reading by
      three readers blind to the clinical results. Sites of abnormal uptake on the foot
      SPECT scan were then compared with the site of known or suspected pathology and
      in 17 patients with planar radiology. RESULTS: The SPECT images produced using
      the uniplanar fan-beam collimators were of good quality in all patients with all
      three readers finding localisation easiest on the sagittal and three-dimensional
      images. In 10 patients abnormalities were found which could explain the patient's
      symptoms or signs and at the site expected from the patient's clinical history.
      In 5 patients there were abnormalities on the bone scan in the ipsilateral foot
      but at a different site, all were interpreted as degenerative disease. 2 patients
      had contralateral degenerative disease to side suggested by the clinical history
      and no abnormality in the bones of the foot with symptoms. One patient had
      bilateral degenerative disease. Planar radiology was normal or unhelpful in 13 of
      the 17 patients in which it was performed. CONCLUSION: SPECT imaging of feet is
      possible and provides accurate localisation of abnormal uptake when performed
      using uniplanar fan-beam collimators with a standard acquisition time of 15 min
      for a double headed gamma camera.

PMID- 14601003
TI  - rCBF SPECT and the acetazolamide test in the evaluation of dementia.
AB  - BACKGROUND: The diagnostic potential of 99mTc-HMPAO following systemic
      administration of the cerebral vasodilator acetazolamide (acetazolamide test) was
      evaluated using regional-cerebral-blood-flow (rCBF) SPECT in patients with
      Alzheimer's disease (AD) or with vascular-type of dementia (VD). METHODS: An
      initial, high-resolution SPELT study was performed with 99mTc-HMPAO, and after 2
      days patients were re-evaluated with 99mTc-HMPAO following systemic
      administration of acetazolamide. Reconstructed SPELT slices were evaluated
      visually and semiquantitatively by a semiautomatic rCBF map method. RESULTS:
      Using 99mTc-HMPAO alone, a bilateral hypoperfusion was found in the temporal
      and/or parietal regions in 33% (6/18) of VD patients and in 70% (23/33) of AD
      patients. The vascular reserve capacity, as determined with the acetazolamide
      test, was not impaired in 22% of the VD patients but in 76% of the AD patients.
      The differences in the perfusion patterns between VD and AD patients were
      statistically different (p < 0.01, Fischer's exact test). Of the 6 VD patients
      with hypoperfusion (bilateral temporal and/or parietal), 4 had a decreased
      vascular reserve capacity as determined in the acetazolamide test. Decreased
      reserve capacity was found in only 4 out of 25 patients with AD. CONCLUSIONS: The
      acetazolamide test is helpful in rCBF SPECT to differentiate VD from AD.

PMID- 14601004
TI  - Cerebral blood flow assessed by brain SPECT with 99mTc-HMPAO utilising the
      acetazolamide test in systemic lupus erythematosus.
AB  - BACKGROUND: Cerebrovascular diseases are one of the most important complications
      of systemic lupus erythematosus (SLE). The diagnostic imaging of neuropsychiatric
      SLE complications presents many problems. This study was undertaken to
      investigate cerebral blood flow char s and its reactivity to hypercapnia by means
      of acetazolamide test in SLE patients. METHODS: Brain SPELT studies using 99mTc
      HMPAO were performed in 50 patients with SLE. Acetazolamide test was performed in
      35 patients 3 days after the baseline study by means of repetitive scanning 20
      min after i.v. injection of 1.0 g of acetazolamide. RESULTS: Significant
      interhemispheric hypoperfusion areas were shown in 76.3% of all patients, 83.8%
      symptomatic and 63.1 % asymptomatic. Patients with antiphospholipid syndrome
      showed multifocal perfusion deficits. The reaction of cerebral perfusion to
      acetazolamide was heterogenous and showed increase, decrease, no change or mixed
      reaction of baseline-study-found focal hypoperfusion. Acetazolamide test revealed
      hypoperfusion in two patients with normal baseline study. MRI scanning revealed
      cerebral lesions in 41 % of patients. CONCLUSIONS: CBF asymmetries in symptomatic
      and asymptomatic patients with SLE are frequent. Regional CBF alterations seem to
      be different in patients with and without antiphospholipid syndrome. The part of
      the patients with SLE shows no or paradoxically inversed reaction to
      acetazolamide.

PMID- 14601005
TI  - Bone SPECT with quantitation for the diagnosis of periodontitis.
AB  - METHODS: A radionuclide method based on single photon emission computed
      tomography (SPECT) for the diagnosis of periodontitis is presented. Nineteen
      consecutive patients, 13 with periodontitis and a control group of 6 healthy
      subjects, were studied. Technetium-99m methylene diphosphonate was used as a bone
      seeking radiopharmaceutical. The tomographic slices corresponding to the alveolar
      crest of the mandible and the maxilla were used for reconstruction. The upper and
      the lower jaws were divided into segments and the mineral metabolism was assessed
      semiquantitatively. RESULTS: Our preliminary results suggest that the method may
      play a role in detecting the regions of the alveolar bone affected by the
      periodontal disease and in the assessment of the activity of the pathological
      process.

PMID- 14601006
TI  - Verification of 99mTc-ethylenedicysteine (99mTc-EC) distribution model in the
      organism.
AB  - BACKGROUND: The aim of the present study was an attempt to verify the systemic
      distribution of 99mTC-ethylenedicysteine by means of the open two-compartment
      model. METHODS: In order to accomplish this, 99mTc-EC clearance was determined in
      21 patients as: two-compartmental model-based plasma clearance, and a urinary
      clearance, i.e. utilising the 99mTc-EC activity excreted with urine during a
      finite time interval. RESULTS: There is a close correlation (r = 0.97) between
      the clearance values determined according to these two methods, and the
      rectilinear orthogonal correlation equation assumes a C1ECu = 1.03656C1ECp -
      18.064 form. The slope of the line does not differ significantly from unity. The
      shift of the correlation line along the X-axis indicates a minor excretion of the
      radiopharmaceutical also by routes different from the urinary tract, e.g. with
      the bile. CONCLUSIONS: The performed comparison of the clearance values has
      proved that distribution of 99mTc-EC in the organism is consistent with the open
      two-compartment model.

PMID- 14601007
TI  - 99m Tc-ethylenedicysteine (99mTc-EC) renal clearance determination error for the
      multiple- and single-sample methods.
AB  - BACKGROUND: The aim of this work has been to assay determination error values for
      the clearance determined by single- and multi-sample method and to compare the
      error values obtained for both methods. METHODS: The assay has been conducted by
      two independent methods (Monte Carlo simulation, total differential). RESULTS:
      The results indicate that the relative root mean square error of the clearance
      determination by multisample method is practically constant above CI values 150
      ml/min and amounts to ab +/-3-4%. For values below 150 ml/min the error increases
      and reaches +/-12% at CI=70 ml/min. The one sample method is less accurate and
      error increases from +/-(8-9)% 550 ml/min to +/- 25% at 70 ml/min. Moreover, for
      the multisample method the error estimated from total differential exceeds that
      obtained from Monte Carlo produced by factory of 3 to 4. For the one sample
      clearance determination both error estimates yield similar results. In both
      methods of clearance determination inaccurate pipetting makes a dominant
      contribution to the overall error. CONCLUSIONS: Form monitoring of patients'
      condition the multisample method should be employed. The use of one sample method
      should be limited to screening tests and for obtaining additional information,
      supplementing the dynamic scintigraphic studies

PMID- 14601009
TI  - Nuclear medicine in children.

PMID- 14601008
TI  - Investigation of gamma camera detector uniformity using a dynamic line phantom.
AB  - BACKGROUND: Investigation of the applicability of the dynamic line phantom for
      determination o the uniformity of circular and rectangular field-of-view gamma
      cameras. METHODS: Count rate - activity and uniformity - count rate functions
      were determined by the dynamic line phantom on three circular field-of-view gamma
      cameras with 37 PMTs, on one circular field of view camera with 19 PMTs, and on
      one rectangular field-of view gamma camera with 59 PMTs, with and without a
      collimator. For an evaluation of the efficacy of the dynamic line phantom, the
      results were compared with the uniformity values obtained with a 99mTc point
      source and a 57-Co sheet source. RESULTS: In the optimum count rate range (20,000
      30,000 cps for a circular field-of-view, 15,000-65,000 cps for a rectangular
      field-of-view) determined individually for each gamma camera, the uniformity
      values obtained with the dynamic line phantom did not differ statistically from
      the refined with the 99mTc point source or the 57-Co sheet source. CONCLUSIONS:
      The dynamic line phantom is suitable for the determination of detector
      uniformity, but the measurements should be performed within a well-defined
      activity (count rate) interval.

PMID- 14601010
TI  - Nuclear medicine applications in oncology.

PMID- 14601011
TI  - Methods for mid-course corrections in clinical trials with survival outcomes.
AB  - Interim monitoring of randomized controlled clinical trials often requires that
      the assumptions under which the trial was designed be evaluated and that
      appropriate design modifications be made. Furthermore, if there is little hope of
      ultimately demonstrating benefit, the study may be terminated on either ethical
      or economic grounds. Design modifications may be made based on either blinded or
      unblinded analyses. Since observed patterns of recruitment and patient outcomes
      may differ from those required by standard methods, specialized tools may be
      required to perform the necessary computations. In this paper we demonstrate how
      the Markov chain model of Lakatos can accommodate arbitrary observed patterns of
      recruitment, hazard rates, and other design parameters for performing mid-course
      corrections in trials with survival outcomes.

PMID- 14601012
TI  - Proportion of treatment effect (PTE) explained by a surrogate marker.
AB  - In time-varying covariate analysis of clinical survival data, it is often of
      interest to estimate the proportion of treatment effect (PTE), along with its
      confidence intervals, explained by a surrogate marker. The conventional procedure
      for such an analysis fits data into two working models separately to estimate the
      treatment effects before and after adjustment of the covariate. The construction
      of confidence intervals for the PTE under the conventional procedure lacks
      support by standard statistical software such as SAS, and could be very
      computationally demanding even after the support is available in the future. To
      overcome this problem, we propose a new procedure to simplify the computation.
      Under the new procedure, the treatment effects before and after adjustment of the
      covariate are simultaneously estimated from a single model. More important than
      saving computational effort, the new procedure can also be effectively applied to
      multiple-covariate models for the decomposition of overall treatment effect and
      for the comparison of PTE among several surrogate markers. The new procedure is
      applied to the motivating data example from the LIFE study, and demonstrates
      flexibility that the conventional procedure currently lacks.

PMID- 14601013
TI  - Selecting the best treatment in designed experiments.
AB  - A common question in biological experimentation is concerned with finding an
      optimal level for a treatment using data obtained from a designed experiment. For
      example, an experiment might concern a group of hyperactive adolescent males that
      have been grouped into blocks according to some relevant factors. Within each
      group the subjects are randomly assigned to several treatments for hyperactivity.
      An important aspect of the study would then be determining which of the treatment
      options is most effective in reducing hyperactivity in the subjects. Basing such
      a determination directly on the estimated treatment effects may be unreliable
      because of the inherent variability associated with the estimates. Other methods,
      such as multiple comparison procedures and best subset selection procedures can
      also be applied to this problem. Unfortunately, such procedures are often
      difficult to interpret and rely on assumptions that may not be appropriate for
      the experiment under consideration. In this paper we develop a method of
      assigning a confidence level to each treatment that measures how confident we are
      that each treatment is optimal. The method for assigning the confidence levels is
      based on a more general methodology developed for the problem of regions, where
      one assigns levels of confidence that an unknown parameter is within specified
      subsets of the parameter space. The actual computation of the confidence levels
      is based on the bootstrap. The method is applied to an example and is studied
      empirically.

PMID- 14601014
TI  - ROC methodology within a monitoring framework.
AB  - Receiver operating characteristic (ROC) methodology is widely used to evaluate
      and compare diagnostic tests. Generally, each diagnostic test is applied once to
      each subject in a population and the results, reported on a continuous scale, are
      used to construct the ROC curve. We extend the standard method to accommodate a
      framework in which the diagnostic test is repeated over time to monitor for
      occurrence of an event. Unlike the usual situation in which event status is
      static, the problem we address involves event status that is not constant over
      the monitoring period. Subjects generally are classified as non-events, or
      controls, until they experience events that convert them to cases. Viewing the
      data as incomplete discrete failure time data with time-varying covariates,
      potentially useful diagnostic markers can be related appropriately in time with
      the true condition and varying amounts of information per individual can be taken
      into account. The ROC curve provides an assessment of the performance of the test
      in combination with the schedule of testing. Within this framework, a
      computational simplification is introduced to calculate variances and covariances
      for the areas under the ROC curves. Periodic monitoring for reperfusion following
      thrombolytic treatment for acute myocardial infarction provides a detailed
      example, whereby the lengths of the testing interval combined with different
      diagnostic markers are compared.

PMID- 14601015
TI  - The roles of birth inputs and outputs in predicting health, behaviour and test
      scores in early childhood.
AB  - The goal of this study is to address directly the predictive value of birth
      inputs and outputs, particularly birth weight, for measures of early childhood
      development in a simultaneous equations modelling framework. Strikingly, birth
      outputs have virtually no structural/causal effects on early childhood
      developmental outcomes, and only maternal smoking and drinking during pregnancy
      have some effects on child height. Not surprisingly, family child-rearing
      environment has sizeable negative and positive effects on a behavioural problems
      index and a mathematics/reading test score, respectively, and a mildly surprising
      negative effect on child height. Despite little evidence of a structural/causal
      effect of birth weight on early childhood developmental outcomes, our results
      demonstrate that birth weight nonetheless has strong predictive effects on early
      childhood outcomes. Furthermore, these effects are largely invariant to whether
      family child-rearing environment is taken into account. Family child-rearing
      environment has both structural and predictive effects on early childhood
      outcomes, but they are largely orthogonal and in addition to the effects of birth
      weight.

PMID- 14601016
TI  - A competing-risks nomogram for sarcoma-specific death following local recurrence.
AB  - The majority of staging systems focus on the definition of stage, and, therefore,
      prediction of prognosis. In the current era of clinical trial research, it has
      become apparent that the clinical stage alone is not sufficient to assess patient
      risk of treatment failure. As the number of biological markers increases, our
      ability to partition the traditional disease classification system improves, and
      our ability to predict patient success continues to increase. One approach to
      quantifying individual patient risk is through the nomogram. Nomograms are
      graphical representations of statistical models, which provide the probability of
      treatment outcome based on patient-specific covariates. We will focus on the use
      of the nomogram when the response variable is time to failure and there are
      multiple, possibly dependent, competing causes of failure. In this setting,
      estimation of the failure probability through direct application of the Cox
      proportional hazards model provides the probability of failure (for example,
      death from cancer) assuming failure from a dependent competing cause will not
      occur. In many clinical settings this is an unrealistic assumption. The purpose
      of this study is to illustrate the use of the conditional cumulative incidence
      function for providing a patient-specific prediction of the probability of
      failure in the setting of competing risks. A competing risks nomogram is produced
      to estimate the probability of death due to sarcoma for patients who have already
      developed a local recurrence of their initially treated soft-tissue sarcoma.

PMID- 14601017
TI  - Measuring explained variation in linear mixed effects models.
AB  - We generalize the well-known R(2) measure for linear regression to linear mixed
      effects models. Our work was motivated by a cluster-randomized study conducted by
      the Eastern Cooperative Oncology Group, to compare two different versions of
      informed consent document. We quantify the variation in the response that is
      explained by the covariates under the linear mixed model, and study three types
      of measures to estimate such quantities. The first type of measures make direct
      use of the estimated variances; the second type of measures use residual sums of
      squares in analogy to the linear regression; the third type of measures are based
      on the Kullback-Leibler information gain. All the measures can be easily obtained
      from software programs that fit linear mixed models. We study the performance of
      the measures through Monte Carlo simulations, and illustrate the usefulness of
      the measures on data sets.

PMID- 14601018
TI  - Modelling discrete time survival data with random slopes: evaluating
      haemodialysis centres.
AB  - We propose a hierarchical discrete time survival model to analyse registry data
      on haemodialysis patients in Rio de Janeiro, Brazil, collected at different
      dialysis centres. Our aim is to estimate differences in hazard ratios
      attributable to variation in dialysis centre performance, after adjusting for
      further observed covariates both at the individual and centre level. The proposed
      model allowed for the estimation of a residual calendar time trend varying across
      dialysis centres through the adoption of a random slope model. These calendar
      time trends turned out to have significant variation, after adjustment for
      important observed covariates. The technique can be easily adapted to other
      diseases as long as survival time is the measurement of interest.

PMID- 14601019
TI  - Estimation of kinetic parameters in graphical analysis of PET imaging data.
AB  - Positron emission tomography (PET) imaging is a useful tool for quantifying
      various aspects of the distribution of neuroreceptors throughout the human brain
      in vivo. A typical analysis consists of applying a pharmacokinetic model to the
      data, estimating the parameters of the model using non-linear least squares
      methods, then taking the appropriate function of estimated model parameters as a
      final estimate of the parameter(s) of interest. As an alternative for fitting
      these models, it has been shown previously that taking a particular
      transformation of the data results in two variables that have a linear
      relationship, and that the slope of this linear relationship is the parameter of
      primary interest. However, estimating the slope using ordinary least squares
      (OLS) regression results in a large negative bias. By rearranging the terms in
      the relationship, the problem may be reformed to allow direct application of
      standard estimation principles. Estimators resulting from this approach are shown
      via simulation to have better estimation properties as compared to the OLS
      estimators.

PMID- 14601021
TI  - Defining regulatory elements in the human KAI1 (CD 82) metastasis suppressor
      gene.
AB  - The human KAI1 metastasis suppressor gene encodes for a 267 amino acid plasma
      membrane glycoprotein, which has four transmembrane domains and one large and one
      small extracellular domain. Plasma membrane expression of KAI1 is downregulated
      during the progression of several cancers to a metastatic state, including
      prostate, lung, and pancreatic cancers. To elucidate the mechanisms for this
      downregulation, an understanding of its transcriptional regulation is critical.
      Therefore, a set of luciferase reporter gene plasmid constructs were generated
      containing various 5' flanking regions to the transcription initiation site, with
      or without the first exon and a portion of the first intron of the KAI1 gene.
      These constructs were transfected into a series of normal and malignant prostate
      cell lines as well as fibroblasts and the resultant luciferase activities used to
      define the regulatory elements for expression of the KAI1 gene. Using this
      approach, the minimal KAI1 promoter was found to be 0.5 kb in size and contains
      two regions. The first region includes the 197 bp 5' to the transcription
      initiation site and the second region includes the first exon and a portion of
      first intron (i.e., +1 to +351 bp). This combined region result in positively
      regulated strong, but not epithelial specific, luciferase expression. In addition
      to this minimal promoter element from -197 to +351 bp, there is a second
      regulatory element further upstream (i.e., -735 to -197 bp), which negatively
      regulates luciferase expression. Additional studies of Marreiros et al. (Gene
      302:155, 2003) have documented that a third regulatory element even further 5'
      (i.e., -922 to -846 bp) encodes an enhancer for the KAI1 gene.

PMID- 14601022
TI  - Where are the prostate cancer genes?--A summary of eight genome wide searches.
AB  - BACKGROUND: There is strong evidence for genetic susceptibility to prostate
      cancer, but most of the genes underlying this susceptibility remain to be
      identified. METHODS: We reviewed the results of eight genome-wide linkage
      searches based on 1,293 families with multiple cases of prostate cancer. RESULTS:
      Across these studies, 11 linkage peaks with LOD scores in excess of 2 were
      identified. However, no chromosomal region was reported as significant at this
      level by more than one study and only one corresponded to a peak previously
      suggested by another group. CONCLUSIONS: These results indicate that prostate
      cancer is genetically complex, and that combined analyses of large family sets
      will be required to evaluate reliably the linkage evidence.

PMID- 14601023
TI  - Results of a genome-wide linkage analysis in prostate cancer families ascertained
      through the ACTANE consortium.
AB  - BACKGROUND: The aggregation of prostate cancer within families suggests a major
      inherited component to the disease. Genetic linkage studies have identified
      several chromosomal regions that may contain prostate cancer susceptibility loci,
      but none has been definitively implicated. METHODS: We performed a genome-wide
      linkage search based on 64 families, 63 with at least 3 cases of prostate cancer,
      ascertained in five countries. The majority of cases from these centers presented
      with clinically detected disease. Four hundred and one polymorphic markers were
      typed in 268 individuals. Multipoint heterogeneity analysis was conducted under
      three models of susceptibility; non-parametric analyses were also performed.
      RESULTS: Some weak evidence of linkage, under at least one of the genetic models,
      was observed to markers on chromosomes 2 (heterogeneity LOD (HLOD) = 1.15, P =
      0.021), 3 (HLOD = 1.25, P = 0.016), 4 (HLOD = 1.28, P = 0.015), 5 (HLOD = 1.20, P
      = 0.019), 6 (HLOD = 1.41, P = 0.011), and 11 (HLOD = 1.24, P = 0.018), and in two
      regions on chromosome 18 (HLOD = 1.40, P = 0.011 and HLOD = 1.34, P = 0.013).
      There were no HLOD scores greater than 1.5 under any model, and no locus would be
      predicted to explain more than half of the genetic effect. No evidence in favor
      of linkage to previously suggested regions on chromosomes 1, 8, 17, 20, or X was
      found. CONCLUSIONS: Genetic susceptibility to prostate cancer is likely to be
      controlled by many loci, with no single gene explaining a large fraction of the
      familial risk. Pooling of results from all available genome scans is likely to be
      required to obtain definitive linkage results.

PMID- 14601024
TI  - Genome-wide scan for linkage in finnish hereditary prostate cancer (HPC) families
      identifies novel susceptibility loci at 11q14 and 3p25-26.
AB  - BACKGROUND: In order to identify predisposition loci to hereditary prostate
      cancer (HPC), we performed a genome-wide linkage analysis using samples from a
      genetically homogeneous population, with 13 Finnish multiplex prostate cancer
      families. METHODS: Altogether 87 DNA samples were genotyped from 13 families.
      Logarithm-of-odds (LOD) scores were calculated for all autosomes using FASTLINK
      and GENEHUNTER designating all unaffected men and all women as unknown. RESULTS:
      The highest LOD scores in the affected-only analyses were found at 11q14, where
      the two-point LOD score was 2.97 (theta = 0.0 at D11S901), GENEHUNTER
      heterogeneity LOD (HLOD) of 3.36, and a non-parametric-linkage (NPL) score of
      2.67 (P = 0.008). A second positive site was at 3p25-26, with a two-point LOD
      score of 2.57 (theta = 0.01 at D3S1297), HLOD of 2.15, and NPL score of 2.27 (P =
      0.02). CONCLUSIONS: The results suggest two HPC regions in the Finnish
      population, which have not been reported previously and warrant further study.

PMID- 14601025
TI  - Genome-wide scan of Swedish families with hereditary prostate cancer: suggestive
      evidence of linkage at 5q11.2 and 19p13.3.
AB  - BACKGROUND: Prostate cancer (CaP) is a common disorder with multiple genetic and
      environmental factors contributing to the disease. CaP susceptibility loci can be
      identified through genome-wide scans of high-risk families. METHODS: Allele
      sharing at 405 markers, distributed across the genome, among 50 families with
      hereditary prostate cancer, ascertained throughout Sweden, was evaluated through
      linkage analyses. Genotype data were analyzed utilizing multipoint parametric and
      non-parametric methods. RESULTS: Two regions provided suggestive evidence for
      linkage: 19p13.3 (marker D19S209, LOD = 2.91, P = 0.0001) and 5q11.2 (marker
      D5S407, LOD = 2.24, P = 0.0007). Additional regions with moderate evidence for
      linkage in the complete set of families, or stratified subsets, were observed on
      chromosome 1, 4, 6, 7, 8, and X. CONCLUSIONS: Our results provide strong
      confirmatory evidence of linkage at 19q13.3 and 5q11.2. The lack of confirmation
      of linkage at several loci identified in other genome-wide scans emphasizes the
      need to combine linkage data between research groups.

PMID- 14601026
TI  - Genome-wide scan of brothers: replication and fine mapping of prostate cancer
      susceptibility and aggressiveness loci.
AB  - BACKGROUND: Substantial evidence suggests that genetic factors play an important
      role in both the risk of prostate cancer and its biologic aggressiveness. Here we
      investigate prostate cancer susceptibility and aggressiveness with genome-wide
      linkage analyses of affected brothers. METHODS: We first undertook a new genome
      wide linkage study of 259 brothers with prostate cancer. Our analyses tested
      whether the proportion of marker alleles shared by brothers was correlated with
      disease status or Gleason score. To further clarify 11 linkage regions observed
      here or previously, we genotyped and analyzed an additional 101 finely spaced
      markers in the 259 men, and in 594 previously studied brothers, allowing for a
      pooled genome-wide analysis of 853 affected brothers. RESULTS: In the new study,
      we detected linkage to prostate cancer on chromosome 16q23 (P = 0.009),
      replicating previous results, and to chromosome 11q24 (P = 0.001). In the pooled
      analysis, the 16q23 linkage was strengthened (P = 0.0005), as was our previous
      linkage to chromosome 16p (P = 0.0001), and we detected linkage to chromosome
      2q32 (P = 0.009). When evaluating Gleason score, our new study detected linkage
      to chromosome 7q32 (P = 0.0009), again replicating previous results, and to
      chromosomes 5p15 (P = 0.003), 9q34 (P = 0.009), 10q26 (P = 0.03), and 18p11 (P =
      0.02). In the pooled analysis of Gleason score, we observed stronger linkage to
      chromosome 7q32 (P = 0.0002), but slightly weaker linkage to chromosomes 5q33 (P
      = 0.005) and 19q13 (P = 0.009) than previously reported. In addition, the new
      linkages to chromosomes 10q26 and 18p11 were strengthened (P = 0.0002 and P =
      0.002, respectively). CONCLUSIONS: Our results provide compelling evidence for
      loci harboring prostate cancer susceptibility and tumor aggressiveness genes,
      especially on chromosomes 16q23 and 7q32.

PMID- 14601027
TI  - Genomic scan of 254 hereditary prostate cancer families.
AB  - Hereditary prostate cancer (HPC) is a genetically heterogeneous disease,
      complicating efforts to map and clone susceptibility loci. We have used
      stratification of a large dataset of 254 HPC families in an effort to improve
      power to detect HPC loci and to understand what types of family features may
      improve locus identification. The strongest result is that of a dominant locus at
      6p22.3 (heterogeneity LOD (HLOD) = 2.51), the evidence for which is increased by
      consideration of the age of PC onset (HLOD = 3.43 in 214 families with median age
      of-onset 56-72 years) and co-occurrence of primary brain cancer (HLOD = 2.34 in
      21 families) in the families. Additional regions for which we observe modest
      evidence for linkage include chromosome 7q and 17p. Only weak evidence of several
      previously implicated HPC regions is detected. These analyses support the
      existence of multiple HPC loci, whose presence may be best identified by analyses
      of large, including pooled, datasets which consider locus heterogeneity.

PMID- 14601028
TI  - Genome-wide scan for prostate cancer susceptibility genes in the Johns Hopkins
      hereditary prostate cancer families.
AB  - BACKGROUND: Although the subject of intensive study, the genetic influences
      responsible for familial clustering of prostate cancer remain largely
      unidentified. Genome-wide scans for linkage in prostate cancer families can be
      used to systematically search for genes capable of affecting risk for the
      disease. METHODS: All available family members from 188 families, each having at
      least three first-degree relatives affected with prostate cancer, were genotyped
      at 406 markers distributed across the genome at average intervals of less than 10
      cM. Genotype data was analyzed using primarily a non-parametric, multipoint
      approach, although parametric analyses were performed as well. RESULTS: The
      strongest evidence for linkage was observed at D4S1615, at 4q21 (LOD of 2.8, P =
      0.0002). Two other regions had LOD scores over 2.0: at 9q34 (marker D9S1826, LOD
      = 2.17, P = 0.0008) and at 2q23 (marker D2S151, LOD = 2.03, P = 0.001). An
      additional 12 regions had LOD scores over 1.0, including markers at 1q24-25 and
      7q22 having scores >1.6. Stratifying the linkage results by age of diagnosis
      indicated that the linkages to chromosomes 2 and 4 were strongest in families
      with early and late ages of diagnosis, respectively. CONCLUSIONS: Our data
      implicate several new loci as harboring prostate cancer susceptibility genes, and
      provide confirmatory evidence of linkage at several loci identified previously in
      other genome-wide scans, including the three regions (4q21, 9q34, and 2q23) with
      strongest evidence for prostate cancer linkage. These data also emphasize the
      need to combine linkage data from large numbers of prostate cancer families in
      efforts to effectively address the extensive heterogeneity that characterizes
      genetic aspects of this disease.

PMID- 14601029
TI  - Genome-wide scan for prostate cancer susceptibility genes using families from the
      University of Michigan prostate cancer genetics project finds evidence for
      linkage on chromosome 17 near BRCA1.
AB  - BACKGROUND: Previous linkage studies have suggested prostate cancer
      susceptibility genes located on chromosomes 1, 20, and X. Several putative
      prostate cancer candidate genes have also been identified including RNASEL, MSR1,
      and ELAC2. Presently, these linkage regions and candidate genes appear to explain
      only a small proportion of hereditary prostate cancer cases suggesting the need
      for additional whole genome analyses. METHODS: A genome-wide mode-of-inheritance
      free linkage scan, using 405 genetic markers, was conducted on 175 pedigrees, the
      majority containing three or more affected individuals diagnosed with prostate
      cancer. Stratified linkage analyses were performed based on previously
      established criteria. RESULTS: Results based on the entire set of 175 pedigrees
      showed strong suggestive evidence for linkage on chromosome 17q (LOD = 2.36),
      with strongest evidence coming from the subset of pedigrees with four or more
      affected individuals (LOD = 3.27). Race specific analyses revealed strong
      suggestive evidence for linkage in our African-American pedigrees on chromosome
      22q (LOD = 2.35). CONCLUSIONS: Genome-wide analysis of a large set of prostate
      cancer families indicates new areas of the genome that may harbor prostate cancer
      susceptibility genes. Specifically, our linkage results suggest that there is a
      prostate cancer susceptibility gene on chromosome 17 that is independent of
      ELAC2. Further research including combined analyses of independent genome-wide
      scan data may clarify the most important regions for future investigation.

PMID- 14601030
TI  - Genome linkage screen for prostate cancer susceptibility loci: results from the
      Mayo Clinic Familial Prostate Cancer Study.
AB  - Prostate cancer is one of the most common cancers among men and has long been
      recognized to occur in familial clusters. Brothers and sons of affected men have
      a twofold to threefold increased risk of developing prostate cancer. However,
      identification of genetic susceptibility loci for prostate cancer has been
      extremely difficult. Several putative loci identified by genetic linkage have
      been reported to exist on chromosomes 1 (HPC1, PCAP, and CAPB), X (HPCX), 17
      (HPC2), and 20 (HPC20), with genes RNASEL (HPC1) and ELAC2 (HPC2) tentatively
      defined. In this study, we report our genome linkage scan in 160 prostate cancer
      families, using the ABI Prism Linkage Mapping Set Version 2 with 402
      microsatellite markers. The most significant linkage was found for chromosome 20,
      with a recessive model heterogeneity LOD score (HLOD) of 4.77, and a model-free
      LOD score (LOD - ZLR) of 3.46 for the entire group of pedigrees. Linkage for
      chromosome 20 was most prominent among families with a late age of diagnosis
      (average age at diagnosis >/= 66 years; maximum LOD - ZLR = 2.82), with <5
      affected family members (LOD - ZLR = 3.02), with presence of hereditary prostate
      cancer (LOD - ZLR = 2.81), or with no male-to-male transmission of disease (LOD -
      ZLR = 3.84). No other chromosome showed significant evidence for linkage.
      However, chromosomes 6 and X showed suggestive results, with maximum LOD - ZLR
      values of 1.38 and 1.36, respectively. Subset analyses suggest additional
      chromosomal regions worth further follow-up.

PMID- 14601031
TI  - Heterogeneity and the genetics of bipolar disorder.

PMID- 14601032
TI  - Anticipation and repeat expansion in bipolar disorder.
AB  - Anticipation is the phenomenon whereby a disease becomes more severe and/or
      presents with earlier onset as it is transmitted down through generations of a
      family. The only known mechanism for true anticipation is a class of mutations
      containing repetitive sequences exemplified by the pathogenic trinucleotide
      repeat. Studies of bipolar disorder (BPD) are consistent with the presence of
      anticipation and, by inference, the possibility that trinucleotide repeats
      contribute to this disorder, although it is possible that these data are the
      result of methodological problems. On the assumption that anticipation in BPD may
      be real, several surveys of the genome of BPD probands for large trinucleotide
      repeats have been conducted, as have studies of many repeat-containing candidate
      genes. No pathogenic triplet repeat has yet been unambiguously implicated.

PMID- 14601033
TI  - Pharmacogenetics and mood stabilization in bipolar disorder.
AB  - Bipolar disorder is a severe psychiatric disease characterized by varying
      treatment response among individual patients. Effects of certain treatments, for
      instance, lithium, can be predicted from clinical characteristics of patients and
      their family histories. This led to a suggestion that a treatment response could
      identify subtypes of bipolar disorder particularly suited for gene-mapping
      studies. In this paper we review family and molecular studies of bipolar disorder
      responsive to lithium, as well as studies aiming to identify polymorphisms
      associated with the treatment response itself. While molecular genetic research
      and gene expression studies promise to bring new insights into the
      pathophysiology of the illness and the nature of treatment response, and thus
      provide new information for better treatment of bipolar disorder in the future,
      results from family studies and studies of clinical correlates of treatment
      response may already be utilized in the management of bipolar disorder.

PMID- 14601034
TI  - Studies of offspring of parents with bipolar disorder.
AB  - Children and adolescents who are the biological offspring of individuals with
      bipolar disorder (BD) (bipolar offspring) represent a population rich in
      potential for revealing important aspects in the development of BD. Multiple
      cross-sectional assessments of psychopathology in bipolar offspring have
      confirmed high incidences of BD, as well as mood and behavioral disorders, and
      other psychopathology in this population. Longitudinal studies of offspring have
      begun to shed light on precursors of BD development. Other assessments of bipolar
      offspring have included dimensional reports of psychiatric and psychosocial
      functioning, temperament assessments, and descriptions of family environments and
      parenting styles. Neurobiological studies in bipolar offspring are just beginning
      to yield findings that may be related to the underlying neuropathophysiology of
      BD. The future holds promise for longitudinal studies of bipolar offspring
      incorporating all of these facets, including genetic analyses, to further
      elucidate the factors involved in the evolution of BD.

PMID- 14601035
TI  - Genetic linkage and association studies in bipolar affective disorder: a time for
      optimism.
AB  - Genetic research on complex diseases is beginning to bear fruit, with the
      successful identification of candidate susceptibility genes in diabetes, asthma,
      and other illnesses. Similar success is on the horizon for bipolar affective
      disorder (BPAD), but significant challenges remain. In this review, we outline
      the basic concepts of linkage and association mapping for complex phenotypes. We
      point out important caveats inherent in both approaches, and review guidelines on
      the interpretation of linkage statistics and significance thresholds. We then
      apply these concepts to an evaluation of the present status of genetic linkage
      and association studies in BPAD. The challenges posed by locus heterogeneity,
      phenotype definition, and sample size requirements are given a detailed
      treatment. Despite these challenges, we argue that the way ahead remains firmly
      rooted in linkage studies, complemented by association studies in linked regions.
      This is the only truly genome-wide approach currently available; it has succeeded
      in other complex phenotypes, and it is the surest strategy for mapping
      susceptibility genes in BPAD. Once these genes are identified, genetic mapping
      methods will yield to the other methods of 21st-century molecular biology as we
      begin to elucidate the pathophysiology of BPAD.

PMID- 14601036
TI  - Family, twin, and adoption studies of bipolar disorder.
AB  - Family, twin, and adoption studies have been essential in defining the genetic
      epidemiology of bipolar disorder over the past several decades. Family studies
      have documented that first-degree relatives of affected individuals have an
      excess risk of the disorder, while twin studies (and to a lesser extent, adoption
      studies) suggest that genes are largely responsible for this familial
      aggregation. We review these studies, including the magnitude of familial risk
      and heritability estimates, efforts to identify familial subtypes of bipolar
      disorder, and the implications of family/genetic data for validating nosologic
      boundaries. Taken together, these studies indicate that bipolar disorder is
      phenotypically and genetically complex.

PMID- 14601037
TI  - Evidence for shared susceptibility in bipolar disorder and schizophrenia.
AB  - This article reviews evidence that bipolar disorder (BPD) and schizophrenia (SZ)
      share familial risk characteristics. The topic is introduced with a brief
      discussion of various shared epidemiologic characteristics of SZ and BPD. Family
      studies of BPD and SZ, conducted by multiple independent groups of investigators,
      are consistent with partial overlap in familial susceptibility. Given that the
      family study data suggest overlap in familial susceptibility for BPD and SZ,
      several confirmed linkages of BPD or SZ are reviewed, with the conclusion that
      there are five genomic regions for which evidence suggests shared genetic
      susceptibility of BPD and SZ. It is suggested that nosology must be changed to
      reflect the genetic origins of the multiple disorders that are collectively
      described by the terms BPD and SZ.

PMID- 14601038
TI  - Epigenetics and bipolar disorder: new opportunities and challenges.
AB  - Despite significant effort, understanding of the molecular causes and mechanisms
      of bipolar disorder (BD) remains a major challenge. Numerous molecular genetic
      linkage and association studies have been conducted over the last two decades;
      however, the data are quite inconsistent or even controversial. This article
      develops an argument that molecular studies of BD would benefit significantly
      from adding an epigenetic (epiG) perspective. EpiG factors refer to modifications
      of DNA and chromatin that "orchestrate" the activity of the genome, including
      regulation of gene expression. EpiG mechanisms are consistent with various non
      Mendelian features of BD such as the relatively high degree of discordance in
      monozygotic (MZ) twins, the critical age group for susceptibility to the disease,
      clinical differences in males and females, and fluctuation of the disease course,
      including interchanges of manic and depressive phases, among others. Apart from
      the phenomenological consistency, molecular epiG peculiarities may shed new light
      on the understanding of controversial molecular genetic findings. The relevance
      of epigenetics for the molecular studies of BD is demonstrated using the examples
      of genetic studies of BD on chromosome 11p and the X chromosome. A spectrum of
      epiG mechanisms such as genomic imprinting, tissue-specific effects,
      paramutagenesis, and epiG polymorphism, as well as epiG regulation of X
      chromosome inactivation, is introduced. All this serves the goal of demonstrating
      that epiG factors cannot be ignored anymore in complex phenotypes such as BD, and
      systematic large-scale epiG studies of BD have to be initiated.

PMID- 14601039
TI  - The neurobiology of bipolar disorder.
AB  - The neurobiology of bipolar disorder is reviewed. Bipolar disorder is associated
      with alterations in central nervous system (CNS) function from the level of large
      scale brain circuits to intracellular signal transduction mechanisms. Because of
      the broad spectrum over which these abnormalities appear, the causative effects
      are most likely present in the lowest common denominator of all of these systems.
      Current evidence points to subtle alterations in signal transduction that
      reverberate downstream both intra- and extracellularly to produce the symptoms of
      bipolar disorder.

PMID- 14601040
TI  - Psychoanalysis and the Catholic Church in Italy: the role of Father Agostino
      Gemelli, 1925-1953.
AB  - Agostino Gemelli, a Catholic priest, psychiatrist, administrator, and educator,
      was an important figure in the early history of psychoanalysis in Italy. He was
      one of the few establishment figures to grapple with Freud's ideas in Italy
      during the first half of the twentieth century, a period during which Italy,
      compared to the rest of Europe and to the United States, was relatively
      impermeable to psychoanalysis. One of the factors that contributed to this was
      the opposition of the powerful Catholic Church, which identified in
      psychoanalysis a challenge to its authority. The author argues that Father
      Gemelli's shifting positions about psychoanalysis between 1925 and 1953 reflected
      the exigencies of his historical circumstances. Gemelli was able to identify in
      psychoanalysis an integrated view of the human condition in stark opposition to
      the brutal reductionism of psychiatry in Italy at that time, but also encountered
      in it elements intolerable to the Church. Examining specifically what it is that
      Gemelli could accept of psychoanalysis, and what needed to be rejected, between
      1925 and 1953, illustrates the particular challenge posed by psychoanalysis to
      Catholicism in Italy.

PMID- 14601041
TI  - Historical origins of schizophrenia: two early madmen and their illness.
AB  - Schizophrenia is a serious mental illness with a remarkably short recorded
      history. Unlike depression and mania, which are recognizable in ancient texts,
      schizophrenia-like disorder appeared rather suddenly in the psychiatric
      literature of the early nineteenth century. This could mean that the illness is a
      recent disease that was largely unknown in earlier times. But perhaps
      schizophrenia existed, embedded and disguised within more general concepts of
      madness and within the arcane languages and cultures of remote times. Both
      possibilities present major challenges to historical and psychiatric scholarship.
      These challenges are explored in this paper by presenting two "new" cases of
      schizophrenia, one from the eighteenth and one from the fourteenth century. The
      cases suggest that the illness may have existed as early as the medieval period.
      However, establishing the population prevalence of schizophrenia in earlier times
      -and therefore resolving the permanence-recency debate--may not be a feasible
      enterprise.

PMID- 14601042
TI  - Minding experience: An exploration of the concept of "experience" in the early
      French anthropology of Durkheim, Levy-Bruhl, and Levi-Strauss.
AB  - In line with the growing concern with the unexamined reliance upon the concept of
      "experience" in anthropology, this article explores in some detail the various
      usages and definitions of the concept in the work of three of early French
      anthropology's most influential theorists: Emile Durkheim (1858-1918), Lucien
      Levy-Bruhl (1857-1939), and Claude Levi-Strauss (1908-). With its important
      influence on both British and American anthropology, the early French
      anthropological tradition, as epitomized in the writings of these three thinkers,
      has indeed played a pivotal role in shaping many current taken-for-granted
      understandings of the concept of experience in the discipline of anthropology as
      a whole. In the process of exploring how experience is viewed by these three
      scholars, this paper will thus take some initial steps toward the historical
      contextualization of many of the unquestioned assumptions underpinning current
      understandings of experience in the discipline of anthropology and the social
      sciences more generally.

PMID- 14601044
TI  - The IGF-1 receptor in cancer biology.
AB  - The type 1 insulin-like growth factor receptor (IGF-1R) plays an important role
      in the establishment and maintenance of the transformed phenotype. It also has a
      strong antiapoptotic activity and has a significant influence on the control of
      cell and body size. Downregulation of the IGF-1R leads to massive apoptosis of
      cancer cells. These characteristics make it an attractive target for anticancer
      therapy.

PMID- 14601045
TI  - Genetic polymorphisms and modulation of 2-amino-1-methyl-6-phenylimidazo[4,5
      b]pyridine (PhIP)-DNA adducts in human lymphocytes.
AB  - 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the most abundant
      heterocyclic amine derived from food, possibly involved in human carcinogenesis.
      We evaluated the formation of PhIP-DNA adducts in lymphocytes from 76 incident
      colorectal cancer patients likely to be exposed to dietary PhIP. To address the
      role of the metabolic polymorphisms relevant to PhIP-DNA adduct formation, the
      patients were genotyped for common polymorphisms in the N-acetyltransferase (NAT1
      and NAT2), sulfotransferase (SULT1A1) and glutathione S-transferase (GSTM1 and
      GSTA1) genes. PhIP released from adducted DNA after hydrolysis was quantitated by
      liquid chromatography-tandem mass spectrometry. Overall, adducts were 3.24 +/-
      3.58/10(8) nucleotides (mean +/- SD); they were not related to sex, smoking
      habits or age, though levels were not significantly higher in smokers, young
      subjects and high meat consumers. High vegetable intake significantly reduced
      PhIP-DNA adducts (Mann-Whitney U, p = 0.044). Individuals with the GSTM1 null
      genotype showed colon cancer onset at earlier age (58.8 +/- 1.8 vs. 63.5 +/- 1.6
      years; Mann-Whitney U, p = 0.047). None of the genetic polymorphisms studied
      significantly affected PhIP-DNA adducts. However, individuals carrying 2 mutated
      GSTA1 alleles and younger than the median age had higher adduct levels than
      homozygous wild-type and heterozygous ones (Kruskal-Wallis p = 0.0008). In
      conclusion, these preliminary data indicate that PhIP-DNA adducts are formed in
      people likely to be exposed to this carcinogen through the diet, suggesting this
      biomarker may be useful to detect human exposure and DNA damage. Overall, the
      genetic polymorphisms considered had limited effect on PhIP-DNA levels, but young
      people with lower detoxification capacity may form a subgroup particularly
      susceptible to dietary carcinogen.

PMID- 14601046
TI  - DNA adduct formation by the anticancer drug ellipticine in rats determined by 32P
      postlabeling.
AB  - Ellipticine is a potent antineoplastic agent whose mode of action is considered
      to be based mainly on DNA intercalation and/or inhibition of topoisomerase II.
      Recently, we found that ellipticine also forms covalent DNA adducts in vitro and
      that the formation of the major adduct is dependent on the activation of
      ellipticine by cytochrome P450 (CYP). Here, we investigated the capacity of
      ellipticine to form DNA adducts in vivo. Male Wistar rats were treated with
      ellipticine, and DNA from various organs was analyzed by (32)P postlabeling.
      Ellipticine-specific DNA adduct patterns, similar to those found in vitro, were
      detected in most test organs. Only DNA of testes was free of the ellipticine-DNA
      adducts. The highest level of DNA adducts was found in liver (19.7 adducts per
      10(7) nucleotides), followed by spleen, lung, kidney, heart and brain. One major
      and one minor ellipticine-DNA adducts were found in DNA of all these organs of
      rats exposed to ellipticine. Besides these, 2 or 3 additional adducts were
      detected in DNA of liver, kidney, lung and heart. The predominant adduct formed
      in rat tissues in vivo was identical to the deoxyguanosine adduct generated in
      DNA by ellipticine in vitro as shown by cochromatography in 2 independent
      systems. Correlation studies showed that the formation of this major DNA adduct
      in vivo is mediated by CYP3A1- and CYP1A-dependent reactions. The results
      presented here are the first report showing the formation of CYP-mediated
      covalent DNA adducts by ellipticine in vivo and confirm the formation of covalent
      DNA adducts as a new mode of ellipticine action.

PMID- 14601047
TI  - Estimation of the potential for nitrosation and its inhibition in subjects from
      high- and low-risk areas for esophageal cancer in southern China.
AB  - We studied 2 counties in southern China, which are close to each other but show
      very different mortality rates from esophageal cancer. We collected 12 hr urine
      samples and analyzed them for NPRO, other nitrosamino acids, nitrate and ASC. The
      potential for forming NPRO and the effect on inhibition by ASC were recorded.
      Urine was collected after (i) no treatment, (ii) a dose of proline and (iii)
      proline with ASC. Intake and excretion of nitrate were significantly greater in
      the high-risk area. After the proline dose, urinary excretion of NPRO was
      significantly greater in the high-risk area. The inhibitory effect of ASC after
      taking it with proline was less in the high-risk area. Hence, the high-risk area
      showed greater potential for forming NPRO, and this formation was less inhibited
      by ASC. This supports the view that esophageal cancer in this area may be caused
      by nitrosamines formed in vivo, perhaps from nitrite produced by reduction of
      ingested nitrate.

PMID- 14601048
TI  - Heterogeneous expression and association of beta-catenin, p16 and c-myc in
      multistage colorectal tumorigenesis and progression detected by tissue
      microarray.
AB  - Most colorectal carcinomas (CRCs) arise from adenomas through an archetypal
      pathogenic pathway, the adenoma-carcinoma-metastasis sequence. Aberrant
      expression of beta-catenin, p16, E-cadherin and c-myc appears to have played
      important roles in the development and/or progression of CRC, but their precise
      distribution pattern and associations in different pathologic loci along CRC's
      pathogenic pathway have not been thoroughly examined. In this study, a tissue
      microarray (TMA) containing 85 advanced CRCs in different Dukes stages was
      constructed. In each of 85 cases, tissue specimens from normal mucosa and primary
      carcinomas in different layers of the bowel wall were included in the TMA. Tissue
      specimens from matched adenoma, lymph node metastases and distant metastases were
      obtained from 22, 21 and 21 cases, respectively. Expression patterns of beta
      catenin, p16, E-cadherin and c-myc were evaluated by immunohistochemistry. The
      results revealed that nuclear expression of beta-catenin, p16 and c-myc was
      quantitatively increased from normal mucosa to premalignant adenoma, primary
      carcinoma and lymph node metastatic carcinoma; the frequency of nuclear
      overexpression of beta-catenin and p16 in lymph node metastases was significantly
      higher than that in distant metastases (p < 0.05). These results suggest an
      association between nuclear overexpression of beta-catenin and/or p16 and CRC
      lymph node metastasis but not distant metastasis. The results also showed that
      correlative high nuclear expression of beta-catenin and c-myc was observed in
      primary carcinomas involving the serosa and lymph node metastases (p < 0.05) but
      not in other pathologic regions of CRCs, suggesting that the tumor
      microenvironment in different pathologic loci of colorectal tumorigenesis and
      progression may influence c-myc responsiveness to beta-catenin/Tcf activation.

PMID- 14601049
TI  - Comparative evaluation of urokinase-type plasminogen activator receptor
      expression in primary breast carcinomas and on metastatic tumor cells.
AB  - The urokinase-type plasminogen activator receptor (uPAR, CD87) plays a central
      role in the plasminogen activation cascade, which participates in extracellular
      matrix degradation, cell migration and invasion. Here we performed a
      comprehensive immmunohistochemical evaluation of uPAR expression in primary tumor
      cells, tumor-surrounding fibroblasts, lymph node metastases and micrometastatic
      cells in bone marrow of patients with breast carcinomas at the time of primary
      diagnosis. Variable degrees of uPAR staining of tumor cells were observed in 84
      of 93 (90%) carcinomas, whereas intratumoral fibroblasts were uPAR-positive in 70
      (75%) carcinomas. The fraction of uPAR-positive primary tumor cells but not
      fibroblasts was positively correlated with the presence of tumor cells in bone
      marrow (p = 0.037), whereas no correlation with lymph node metastasis was found.
      Immunophenotyping of bone marrow and lymph node specimens revealed expression of
      uPAR on metastatic tumor cells in 10 of 13 and 22 of 23 cases, respectively.
      Direct comparison to the autologous primary tumor cells showed different uPAR
      staining scores in most patients with evidence for both up- and downregulation of
      uPAR on metastatic cells. Our results indicate that uPAR plays an active role in
      breast cancer metastasis and may therefore be a promising target for new biologic
      therapies.

PMID- 14601050
TI  - Decrease of human pancreatic cancer cell tumorigenicity by
      alpha1,3galactosyltransferase gene transfer.
AB  - The enzyme alpha1,3galactosyltransferase synthesizes the alphaGal epitope, a
      carbohydrate structure (Galalpha1,3Galbeta1,4GlcNAc-R), on glycoconjugates in
      lower mammals. The enzyme is absent in humans but large amounts of natural
      antibodies that recognize alphaGal epitopes are present in human serum. It is
      likely that these antibodies contribute to the host defense and participate in
      the hyperacute rejection of xenograft. Previous studies indicated that the
      glycosyltransferase gene transfer into tumoral cells can modify the structure of
      glycoconjugates at the cell surface and, as a consequence, modulates the
      metastatic and tumorigenic behaviors of these cells. The aim of our study was to
      determine whether the expression of alphaGal epitope can modify the
      tumorigenicity of human pancreatic cancer cells. The expression of alphaGal
      epitopes in the human pancreatic cancer cell lines BxPC-3 and Panc-1 was obtained
      by selecting stable cell clones transfected with murine
      alpha1,3galactosyltransferase gene. The expression of the enzyme activity in BxPC
      3 and Panc-1 cells resulted in the formation at the cell surface of alphaGal
      epitopes that are recognized by human anti-alphaGal antibodies. alphaGal epitope
      expression at the surface of pancreatic cancer cells was associated with the
      fixation of complement 1q to human anti-alphaGal antibodies. The alphaGal epitope
      expression also resulted in a delay in the tumoral development of BxPC-3 and Panc
      1 cells in vivo after xenograft transplantation of nude mice. In addition to the
      impairment of the metastatic potential of murine tumor cell lines and the
      activation of immune response, our study provides evidence that the cell surface
      expression of alphaGal epitopes also modulates the tumorigenic behavior of human
      pancreatic cancer cells.

PMID- 14601051
TI  - Expression of TGF-beta type II receptor antisense RNA impairs TGF-beta signaling
      in vitro and promotes mammary gland differentiation in vivo.
AB  - In order to clarify the role of TGF-beta in mammary development and
      tumorigenesis, we investigated the efficacy of full- or partial-length TbetaRII
      antisense RNA specifically to reduce TbetaRII levels in both in vitro and in vivo
      model systems. Here we show that the expression of TbetaRII antisense RNA in
      vitro reduced TbetaRII cell surface expression and inhibited the
      antiproliferative and transcriptional responses to exogenous TGF-beta. Expression
      of full-length TbetaRII antisense RNA in a transgenic mouse model under control
      of the mouse mammary tumor virus promotor resulted in precocious lobuloalveolar
      development of the mammary gland, a phenotype that resembles that of early
      pregnancy. These data demonstrate that TbetaRII plays a critical role in
      maintaining the nondifferentiated character of virgin mammary gland epithelium.

PMID- 14601052
TI  - Selective and nonselective toxicity of TRAIL/Apo2L combined with chemotherapy in
      human bone tumour cells vs. normal human cells.
AB  - Although TRAIL/Apo2L preferably induces apoptosis in tumour cells without
      toxicity in normal cells, many tumour cell types display TRAIL/Apo2L resistance.
      Whether TRAIL/Apo2L in combination with chemotherapy may overcome TRAIL/Apo2L
      resistance while maintaining tumour selectivity remains to be determined. Here,
      we report that while ActD, DOX and CDDP sensitised both OS and Ewing's tumour
      cell lines and normal cells (hOBs, synovial cells, fibroblasts) to TRAIL/Apo2L
      induced apoptosis, the combination of etoposide (VP16) and TRAIL/Apo2L was
      selectively active on tumour cells without affecting normal cells. Sensitisation
      of OS cells and hOBs to TRAIL/Apo2L did not correlate with a compatible change in
      the gene expression profile of the receptors for TRAIL/Apo2L determined by
      quantitative real-time RT-PCR. Also, sensitisation of the TRAIL/Apo2L death
      pathway did not rely entirely on the chemotherapy-induced, caspase-dependent
      cytotoxicity. Further, chemotherapy did not cause a compatible change in
      expression levels of proteins such as Bcl-2, Bcl-x(L), Bax, cIAP2, XIAP and
      survivin. However, ActD, DOX and CDDP downregulated expression of cFLIP in OS
      cells as well as expression of p21 in normal hOBs. Interestingly, while VP16 also
      extinguished cFLIP in OS cells, which were sensitised for TRAIL/Apo2L by VP16,
      VP16 induced cFLIP and enhanced p21 levels in normal hOBs, which remained
      refractory to VP16 plus TRAIL/Apo2L. Together, our data reveal that TRAIL/Apo2L
      combined with certain chemotherapeutic drugs is toxic to bone tumour and normal
      human cells and suggest that cotreatment with TRAIL/Apo2L and VP16 provides an
      attractive approach for selective killing of tumour cells while leaving
      unaffected normal cells.

PMID- 14601053
TI  - Intensified oxidative and nitrosative stress following combined ALA-based
      photodynamic therapy and local hyperthermia in rat tumors.
AB  - Oxidative stress-related changes in tumors upon localized hyperthermia (HT), 5
      aminolevulinic acid-based photodynamic therapy (ALA-PDT) and their combination
      (ALA+HT) were examined after the observation that the antitumor effects of ALA
      PDT could be significantly enhanced upon simultaneous application of HT. Rats
      bearing s.c. DS-sarcomas (0.6-1.0 ml) on the hind foot dorsum were anesthetized
      and underwent one of the following treatments: (i) ALA-PDT (375 mg/kg 5-ALA
      i.v.); (ii) localized HT, 43 degrees C for 60 min; (iii) combined ALA-PDT and HT
      [=ALA+HT]. Appropriate control experiments were also performed. After treatment,
      tumors were excised and rapidly frozen for later analysis of nitrosative stress
      (protein nitration), apoptotic events (TUNEL, caspase activation, DNA and RNA
      fragmentation), expression of heat shock proteins (hsp70 and HO-1), glutathione
      (GSH) levels and glutathione peroxidase (GPx) activity. Protein nitration was
      found to increase upon treatment, being especially pronounced in the ALA+HT
      group, and could partially be related to areas surrounding microvessels. The
      extent of nitrosative stress also correlated well with the appearance of the
      markers of apoptosis and the inhibition of in vivo tumor growth as seen in a
      previous study. GSH levels decreased upon treatment, the reduction being most
      prominent in the ALA-PDT and ALA+HT groups. GPx activity, however, showed a
      significant decrease only in the ALA-PDT group. Whereas hsp70 expression
      increased upon HT, ALA-PDT caused a decrease, and these opposing effects were
      nullified with ALA+HT. The results obtained point to a number of cellular
      mechanisms-including effects on cellular defense mechanisms and an abrogation of
      the heat shock defense mechanism-that may interact to achieve the potentiated
      tumor response rate seen in vivo upon combined treatment.

PMID- 14601054
TI  - Gene transfer of alpha1,3-fucosyltransferase increases tumor growth of the PC-3
      human prostate cancer cell line through enhanced adhesion to prostatic stromal
      cells.
AB  - Elevated expression of sialyl Lewis X has been postulated to be a prognostic
      indicator of prostate cancer. However, direct evidence for the relationship
      between increased expression of sialyl Lewis X and malignancy of prostate cancer
      is still lacking. To determine whether increased levels of sialyl Lewis X leads
      to malignancy in prostate tumor, we transfected the human prostate cancer cell
      line PC-3 with alpha1,3-fucosyltransferase III (FTIII) to obtain stable
      transfectants, PC-3-FTIII lines, that highly express sialyl Lewis X. When
      inoculated in the prostate of nude mice, PC-3-FTIII cells produced large prostate
      tumors, while mock-transfected PC-3 cells, which are negative for sialyl Lewis X
      antigen, produced small prostate tumors. The aggressive tumor formation by PC-3
      FTIII cells was inhibited by preincubation of the tumor cells with anti-sialyl
      Lewis X antibody, by the presence of sialyl Lewis X oligosaccharide or by
      selectin ligand mimic peptide but not by control peptide. PC-3-FTIII cells and
      mock-transfected PC-3 cells exhibited no significant difference in cell numbers
      when cultured in vitro. Remarkably, PC-3-FTIII adhered to prostatic stromal cells
      in vitro with higher affinity than mock-transfected PC-3. Such adhesion was
      inhibited by preincubation of PC-3-FTIII cells with antisialyl Lewis X antibody,
      by the addition of sialyl Lewis X oligosaccharide or by selectin ligand mimic
      peptide. However, anti-E-selectin, anti-P-selectin or anti-L-selectin antibodies
      did not inhibit the adhesion of PC-3-FTIII cells to the stromal cells. These
      results suggest that prostate cancer cells gain aggressiveness through adhesive
      interaction with prostatic stromal cells by a novel mechanism involving sialyl
      Lewis X.

PMID- 14601055
TI  - Thymic function and immunoglobulin mutation genotype in B-cell chronic
      lymphocytic leukemia patients.
AB  - B-cell chronic lymphocytic leukemia (B-CLL) is characterized by a profound
      dysregulation of the host's immune system at both the humoral and cellular level.
      We investigated to see if this dysregulation could be due partly to thymus
      dysfunction by quantifying the number of signal joint T-cell receptor excision
      circles (sjTRECs) in peripheral blood mononuclear cells of 30 untreated B-CLL
      patients at diagnosis and in age-matched healthy controls. sjTRECs were found
      decreased, normal and elevated in 19, 9 and 2 patients, respectively, in
      comparison to age-matched controls. We next speculated that sjTREC levels might
      be related to an accredited B-CLL prognostic marker represented by the somatic
      hypermutation (SHM) status of the variable heavy chain (V(H)) genes. Eight of 17
      patients with SHMs had sjTREC levels in the range of or higher than normal
      donors, whereas only 3 of the 13 patients lacking SHMs had normal sjTREC levels.
      After a 5-year observation period in 16 patients for whom a clinical follow-up
      was available, only 2 of 10 patients with SHMs progressed vs. 5 of 6 patients
      without SHMs and 3 of 7 patients with normal or higher sjTREC levels progressed
      vs. 4 of 9 with low sjTREC levels. Our study demonstrates that sjTREC levels are
      decreased in >60% of B-CLL patients and suggests a potential role of thymus in
      the immune dysfunction of these patients.

PMID- 14601056
TI  - Loss of heterozygosity of chromosome 12p does not correlate with KRAS mutation in
      non-small cell lung cancer.
AB  - Activating mutations of RAS gene families have been found in a variety of human
      malignancies, including lung cancer, suggesting their dominant role in
      tumorigenesis. However, several studies have shown a frequent loss of the wild
      type KRAS allele in the tumors of murine models and an inhibition of oncogenic
      phenotype in tumor cell lines by transfection of wild-type RAS, indicating that
      wild-type RAS may have oncosuppressive properties. To determine whether loss of
      wild-type KRAS is involved in the development of human lung cancer, we
      investigated the mutations of KRAS, NRAS and BRAF in 154 primary non-small cell
      lung cancers (NSCLCs) as well as 10 NSCLC cell lines that have been shown to have
      KRAS mutations. We also determined the loss of heterozygosity status of KRAS
      alleles in these tumors. We detected point mutations of KRAS in 11 (7%) of 154
      NSCLCs, with 10 cases at codon 12 and 1 at codon 61, but no mutations of NRAS or
      BRAF were found. Using the laser capture microdissection technique, we confirmed
      that 9 of the 11 tumors and 7 of the 10 NSCLC cell lines retained the wild-type
      KRAS allele. Among the cell lines with heterozygosity of mutant and wild-type
      KRAS, all of the cell lines tested for expression were shown to express more
      mutated KRAS than wild-type mRNA, with higher amounts of KRAS protein also being
      expressed compared to the cell lines with a loss of wild-type KRAS allele. In
      addition, among 148 specimens available for immunohistochemical analysis, 113
      (76%) showed positive staining of KRAS, indicating that the vast majority of
      NSCLCs continue to express wild-type KRAS. Our findings indicate that the wild
      type KRAS allele is occasionally lost in human lung cancer, and that the
      oncogenic activation of mutant KRAS is more frequently associated with an
      overexpression of the mutant allele than with a loss of the wild-type allele in
      human NSCLC development.

PMID- 14601057
TI  - DNA methylation of RASSF1A, HIN-1, RAR-beta, Cyclin D2 and Twist in in situ and
      invasive lobular breast carcinoma.
AB  - Little is known about epigenetic silencing of genes by promoter hypermethylation
      in lobular breast cancers. The promoter methylation status of 5 cancer-related
      genes (RASSF1A, HIN-1, RAR-beta, Cyclin D2 and Twist) was evaluated in 2 types of
      lobular cancers, in situ (LCIS) and invasive lobular carcinomas (ILC) (n = 32),
      and compared to ductal in situ (DCIS) and invasive (IDC) breast cancers (n = 71).
      By using methylation-specific PCR (MSP), 100% of ILC and 69% of LCIS cases were
      found to have 1 or more hypermethylated genes among the panel of 5 genes
      (compared to 100% IDC and 95% of DCIS). Two or more hypermethylated genes were
      detected per tumor in 79% of invasive and 61% of in situ lobular carcinomas
      compared to 81% of IDC and 77% of DCIS. By contrast, DNA from nearly all normal
      reduction mammoplasty tissues (n = 8) was unmethylated for the 5 genes. The
      methylation profiles of lobular vs. ductal carcinomas with respect to RASSF1A,
      Cyclin D2, RARbeta, and Hin-1 genes were similar, suggesting that gene silencing
      by promoter hypermethylation is likely to be important in both groups of
      diseases. Distinctly different, Twist was hyper- methylated less often in ILC
      (16%, 3/19 cases) than in IDC (56%, 15/27 cases) (p = 0.01). These results
      suggest that these 2 types of tumors share many common methylation patterns and
      some molecular differences. Additional studies might lend further understanding
      into the etiology and clinical behavior of this tumor type.

PMID- 14601058
TI  - Inhibition of tumor cell growth by antibodies induced after vaccination with
      peptides derived from the extracellular domain of Her-2/neu.
AB  - The anti Her-2/neu monoclonal antibody Trastuzumab has strong inhibiting effects
      on tumor growth in vitro and in vivo and is therefore used for immunotherapy in
      breast cancer patients. Due to necessity of frequent applications, however, cost
      intensiveness of Trastuzumab treatment and its limited duration of affectivity,
      an active immunization inducing a perhaps preventive and long-term immunity to
      Her-2/neu remains a desirable goal. We attempted to induce anti Her-2/neu
      antibodies by peptide vaccination and to test their efficacy in inhibiting tumor
      cell growth in vitro. By computer aided analyses, 7 putative B cell epitopes of
      Her-2/neu were defined and synthesized. These peptide epitopes were coupled to
      tetanus toxoid and used for immunization in BALB/c mice. Among these peptides,
      immunizations with 2 single peptides or a combination of 2 peptides induced anti
      peptide antibody levels, primarily of the IgG1 isotype. These antibodies were
      also directed against the native Her-2/neu antigen, as shown in precipitation
      assays and ELISA with cell lysates of the Her-2/neu overexpressing breast cancer
      cell line SK-BR-3. Isolated IgG fractions from immune sera incubated with SK-BR-3
      cells led to a moderate inhibition of the tumor cell growth in vitro, as well as
      to complement dependent cell lyses comparable to that achieved by incubation with
      Trastuzumab. Moreover, peptide immunization in rabbits generated anti-Her 2-neu
      IgG that, in contrast to mouse sera, were able to mediate a 31-46% lysis of SK-BR
      3 cells in ADCC experiments. We conclude from our data that immunization with Her
      2/neu peptides successfully induced humoral immune response with anti-tumor
      activity in an animal model.

PMID- 14601059
TI  - Detection of breast cancer cells in the peripheral blood is positively correlated
      with estrogen-receptor status and predicts for poor prognosis.
AB  - We investigated whether detection of cytokeratin-positive (CK+) cells in the
      peripheral blood (PB) of breast cancer patients before chemotherapy could be a
      prognostic factor. Blood from a total of 92 breast cancer patients was evaluated
      for the presence of CK+ cells. Blood samples were collected before chemotherapy.
      Patients entered in the study included: neoadjuvant (n = 25), adjuvant (n = 42)
      and metastatic (n = 25). Blood samples (10 ml) were centrifuged using a double
      density-gradient to recovering the mononuclear cell (MNC) and granulocyte cell
      (GC) fractions. Subsequently, positive immunomagnetic cell separation was carried
      out to isolating CK+ cells. The enriched cell fraction was cytocentrifuged and
      then immunocytochemically labeled using an anti-cytokeratin antibody. Our results
      indicated that breast tumor cells sediment with both MNC and GC fractions. We
      therefore recommend examination of both fractions in all enrichment protocols.
      CK+ cells in PB were identified in 57 of 92 (62%) patients when MNC and GC
      fractions were assessed (range = 1-61 cells, median = 8). No CK+ cells were
      detected in blood samples of 16 healthy donors. There were significant
      differences in the presence of CK+ cells according to estrogen receptor
      expression (p = 0.049), and lymph node status (p = 0.033), but not to the age,
      menopausal status, type of patient (neoadjuvant, adjuvant or metastatic), TNM
      stage, histological type, progesterone receptor expression, c-erbB2 expression,
      p53 expression or Ki67 expression. Regarding the relationship between tumor size
      (T) and the presence of CK+ cells, a borderline significant trend was observed (p
      = 0.07). The median follow-up of the patients was 21 months and statistical
      analysis (Kaplan-Meier analysis) showed that using the method we present, the
      detection of CK+ cells in PB before starting the chemotherapy in breast cancer
      patients was significantly correlated with both progression-free survival (p =
      0.058) and overall survival (p = 0.003). In conclusion, the present study
      suggests that detection of CK+ cells in PB before chemotherapy might identify
      breast cancer patients with poor prognosis.

PMID- 14601060
TI  - A cross-sectional investigation of breast density and insulin-like growth factor
      I.
AB  - Our study investigated the association of breast cancer risk as assessed by
      mammographic density with insulin-like growth factor I (IGF-I) and one of its
      binding proteins (IGFBP-3) in healthy premenopausal women with different ethnic
      backgrounds. In a cross-sectional design, we analyzed the baseline mammograms and
      fasting serum samples (collected 5 days after ovulation) of premenopausal women
      entering a nutritional intervention. Serum concentrations of IGF-I and IGFBP-3
      were measured by double-antibody ELISA. Mammographic densities were assessed
      using a computer-assisted method. We calculated Spearman correlation coefficients
      between mammographic characteristics and analytes and estimated means of
      mammographic characteristics by quartiles of IGF-I and IGFBP-3 while adjusting
      for age, body mass index (BMI) and reproductive factors. In this group of 240
      women, IGF-I, IGFBP-3 and percent densities did not differ significantly by
      ethnicity. Whereas mammographic densities were not associated with IGF-I, we
      found an inverse relation with IGFBP-3 (r(s) = -0.15, p = 0.02) and a positive
      association with the IGF-I/IGFBP-3 ratio (r(s) = 0.13, p = 0.04). The size of the
      dense areas was not associated with the analytes, but the size of the nondense
      areas was correlated directly with IGFBP-3 (r(s) = 0.20, p = 0.002) and inversely
      with the molar ratio (r(s) = -0.19, p = 0.004). These associations were limited
      to women with a BMI of less than 25 kg/m(2). These results suggest that the
      balance of circulating IGF-I and IGFBP-3 levels may influence the growth of the
      fatty part of the breast more than the epithelial and stromal breast tissue, but
      the exact mechanism of action needs to be explored in more detail.

PMID- 14601061
TI  - Birth weight and risk of breast cancer in a cohort of 106,504 women.
AB  - The possible association between prenatal factors and breast cancer has been
      discussed for more than a decade. Birth weight has been used commonly as a proxy
      measure for intrauterine growth. Whereas some previous studies have found support
      for an association between birth weight and breast cancer, others have been
      inconclusive or found no association. We investigated the relationship between
      birth weight and risk of female breast cancer in a cohort of 106,504 Danish
      women. Birth weights were obtained from school health records on girls born
      between 1930-1975. Information on breast cancer came from linking the cohort with
      the Danish Cancer Registry and the Danish Breast Cancer Cooperative Groups
      Registry. A total of 2,334 cases of primary breast cancer were diagnosed in the
      cohort during 3,255,549 person-years of follow-up among women with birth weight
      between 500-6,000 g. Of these, 922 (40%) were diagnosed with primary breast
      cancer at the age of 50 years or older. A significant association between birth
      weight and breast cancer was found equivalent to an increase in risk of 9% per
      1,000 g increase in birth weight (95% CI 2-17). The increase was observed for all
      age groups, representing both pre- and post-menopausal women, and irrespective of
      tumor characteristics. Adjustment for age at first birth and parity did not
      influence the results. Birth weight is positively associated with risk of breast
      cancer, indicating that prenatal factors are important in the etiology of breast
      cancer.

PMID- 14601062
TI  - Fruits, vegetables and lung cancer: a pooled analysis of cohort studies.
AB  - Inverse associations between fruit and vegetable consumption and lung cancer risk
      have been consistently reported. However, identifying the specific fruits and
      vegetables associated with lung cancer is difficult because the food groups and
      foods evaluated have varied across studies. We analyzed fruit and vegetable
      groups using standardized exposure and covariate definitions in 8 prospective
      studies. We combined study-specific relative risks (RRs) using a random effects
      model. In the pooled database, 3,206 incident lung cancer cases occurred among
      430,281 women and men followed for up to 6-16 years across studies. Controlling
      for smoking habits and other lung cancer risk factors, a 16-23% reduction in lung
      cancer risk was observed for quintiles 2 through 5 vs. the lowest quintile of
      consumption for total fruits (RR = 0.77; 95% CI = 0.67-0.87 for quintile 5; p
      value, test for trend < 0.001) and for total fruits and vegetables (RR = 0.79;
      95% CI = 0.69-0.90; p-value, test for trend = 0.001). For the same comparison,
      the association was weaker for total vegetable consumption (RR = 0.88; 95% CI =
      0.78-1.00; p-value, test for trend = 0.12). Associations were similar between
      never, past, and current smokers. These results suggest that elevated fruit and
      vegetable consumption is associated with a modest reduction in lung cancer risk,
      which is mostly attributable to fruit, not vegetable, intake. However, we cannot
      rule out the possibility that our results are due to residual confounding by
      smoking. The primary focus for reducing lung cancer incidence should continue to
      be smoking prevention and cessation.

PMID- 14601063
TI  - Physical inactivity and percent breast density among Hispanic women.
AB  - Results of epidemiologic studies suggest an inverse association between breast
      cancer risk and physical activity; this is one of the few modifiable breast
      cancer risk factors identified to date. However, only 2 previous studies assessed
      the association between physical activity and the extent of mammographically
      detected fibroglandular breast density, a marker of breast cancer risk. Moreover,
      there has been no study of physical inactivity and percent breast density, nor a
      study of this relationship in Hispanic women, who are less physically active than
      non-Hispanic whites. In the Chicago Breast Health Project, we collected
      information on sociodemographic, reproductive, medical and lifestyle factors and
      percent breast density, assessed quantitatively using full-field digital
      mammography, from 294 Hispanic women. In our study, we examined the independent
      associations of hours per day of physical inactivity with percent breast density
      using multivariate linear regression analysis adjusting for age, education, body
      mass index, parity, menopausal status, use of hormone replacement therapy and
      smoking status. Overall, the mean percent breast density was low (i.e., 17.7%)
      and ranged from 1.9% to 54.6%. There was no difference in percent breast density
      for women who reported 1.5-3.0 hr of physical inactivity per day compared to
      women who reported 0-1 hr per day (beta = -0.08, p = 0.95), but percent density
      was marginally significantly higher for women who were reported at least 3.5 hr
      per day of physical inactivity (beta = 3.18, p = 0.056). Results were similar,
      albeit less statistically significant, in analyses of pre/perimenopausal and
      postmenopausal women separately. These results support the need for further
      research investigating the effect of physical activity on breast cancer risk.

PMID- 14601064
TI  - Cancer in Greenlandic Inuit 1973-1997: a cohort study.
AB  - The increasing westernization of the Arctic countries may influence the very
      particular cancer profile of these populations. Our objective was to investigate
      the development in cancer incidence from 1973 to 1997 in a large and well-defined
      Inuit population in Greenland. Greenland is part of the Danish Kingdom, and
      population statistics covering both countries are available from the same
      registry resource. Data from the Danish Civil Registration System and from the
      Danish Cancer Registry were used to calculate age-standardized cancer incidence
      rates for the periods 1973-1987 and 1988-1997 for persons born in Greenland.
      Using rates for Denmark, sex-specific standardized incidence ratios (SIRs) for
      1988-1997 were calculated. Furthermore, age- and sex-specific incidence rates in
      the 2 periods were calculated for selected cancers. Total cancer incidence
      increased from 248.5 to 277.9 per 100,000 person-years in men and from 269.4 to
      302.2 per 100,000 person-years in women. The incidence of lung, stomach, breast
      and colon cancer increased, whereas the incidence of cervical cancer decreased.
      Compared to the Caucasian population in Denmark, high SIRs were found for cancers
      of the nasopharynx, salivary gland, esophagus, stomach and cervix and low SIRs
      for testis, bladder, prostate, breast and hematologic cancers. Overall cancer
      incidence among Greenlandic Inuit is increasing as a result of increases in
      several cancers that are common in Western populations. A significant increase in
      the incidence of stomach cancer in both sexes, which contrasts global trends for
      this cancer, warrants further investigation.

PMID- 14601065
TI  - The association between stressful life events and breast cancer risk: a meta
      analysis.
AB  - Breast cancer is the most prevalent cancer in women in Western societies. Studies
      examining the relationship between stressful life events and breast cancer risk
      have produced conflicting results. The purpose of this meta-analysis was to
      identify studies on this relationship, between 1966 and December 2002, to
      summarize and quantify the association and to explain the inconsistency in
      previous results. Summary odds ratios and standard errors were calculated, using
      random effect meta-regression analyses, for the following categories: stressful
      life events, death of spouse, death of relative or friend, personal health
      difficulties, nonpersonal health difficulties, change in marital status, change
      in financial status and change in environmental status. The presence of
      publication bias has been explored, and sensitivity analyses were performed to
      identify heterogeneity, using calculation of the percentage of variability due to
      heterogeneity, meta-regression analyses and stratification. Only the categories
      stressful life events (OR = 1.77, 95% CI 1.31-2.40), death of spouse (OR = 1.37,
      95% CI 1.10-1.71) and death of relative or friend (OR = 1.35, 95% CI 1.09-1.68)
      showed a statistically significant effect. Publication bias was identified in
      both stressful life events (p = 0.00) and death of relative or friend (p = 0.02).
      Sensitivity analyses resulted in the identification of heterogeneity in all
      categories, except death of spouse. The results of this meta-analysis do not
      support an overall association between stressful life events and breast cancer
      risk. Only a modest association could be identified between death of spouse and
      breast cancer risk.

PMID- 14601066
TI  - Enhancement of tumor radioresponse by combined treatment with gefitinib (Iressa,
      ZD1839), an epidermal growth factor receptor tyrosine kinase inhibitor, is
      accompanied by inhibition of DNA damage repair and cell growth in oral cancer.
AB  - Molecular blockade of EGFR with either an EGFR MAb or an EGFR TKI enhances the
      radiosensitivity of human SCCs. In the present study, we investigated whether
      treatment with the EGFR TKI gefitinib (Iressa, ZD1839) improves the response to
      radiotherapy in the OSCC cell lines HSC2 and HSC3. We examined potential
      mechanisms that may contribute to the enhanced radiation response induced by
      gefitinib. Growth inhibition was observed in vitro with radiation or gefitinib. A
      cooperative antiproliferative effect was obtained when cancer cells were treated
      with radiation followed by gefitinib. Cells treated with a combination of
      radiation and gefitinib arrested in G(1) and G(2)-M phases, with a decrease in
      the S-phase population. While radiation alone did not significantly affect MEK1/2
      and p38 MAPK autophosphorylation, the combination of gefitinib and radiation
      completely inhibited the downstream signaling of EGFR. Results from DNA damage
      repair analysis in cultured OSCC cells demonstrated that gefitinib had a strong
      inhibitory effect on DNA-PKc pathways after radiation. Tumor xenograft studies
      demonstrated that the combination of gefitinib and radiation caused growth
      inhibition and tumor regression of well-established OSCC tumors in athymic mice;
      tumor volume was reduced from 1,008.2 to 231.4 mm(3) in HSC2 cells (p < 0.01) and
      from 284.2 to 12.4 mm(3) in HSC3 cells (p < 0.01). Immunohistochemical analysis
      of OSCC xenografts revealed that gefitinib caused a striking decrease in tumor
      cell proliferation when combined with radiotherapy. Overall, we conclude that
      gefitinib enhances tumor radioresponse by multiple mechanisms that may involve
      antiproliferative growth inhibition and effects on DNA repair after exposure to
      radiation.

PMID- 14601067
TI  - Novel retinoic acid derivative ABPN has potent inhibitory activity on cell growth
      and apoptosis in cancer cells.
AB  - Retinoids are natural and synthetic derivatives of vitamin A that have great
      promise for cancer therapy and chemoprevention. Of the retinoids developed so
      far, 4-(N-hydroxyphenyl)retinamide (4-HPR or fenretinide) appears to have the
      best therapeutic potential in vitro and in vivo and is currently being tested in
      clinical trials for cancer prevention and therapy. To develop other potentially
      potent antitumor agents, we synthesized 85 retinoid derivatives. In an initial
      screening of these synthetic retinoids using the HCT116 colon cancer cell line,
      we found that 4-amino-2-(butyrylamino)phenyl(2E,4E,6E,8E)-3,7-dimethyl-9-(2,6,6
      trimethyl-1-cyclohexenyl)-2,4,6,8-nonatetraenoate (ABPN or CBG41) induced the
      greatest growth inhibition, with an IC(50) value of 0.6 microM. Subsequent
      studies in other cancer cell lines indicated that ABPN was much more growth
      inhibitory than all-trans retinoic acid or 4-HPR. Compared to 4-HPR, ABPN induced
      5.5- to 70.0-fold more growth inhibition in most cancer cells, with the exception
      of gynecologic cancer cells. In these cells, the antiproliferative effect was
      only 1.5- to 2.8-fold more than 4-HPR. We examined the molecular mechanism
      underlying the difference in growth inhibition between 4-HPR and ABPN. DAPI
      staining, DNA fragmentation, FACS and Western blotting analyses suggest that ABPN
      induced apoptosis by activating caspase-3 and -8, which may result in increased
      PARP cleavage. Unlike 4-HPR, ABPN activated all 3 RAR isotypes to an extent
      similar to AtRA. In addition, ABPN significantly inhibited AP-1 transcriptional
      activity and thus greatly suppressed the expression of the matrix
      metalloproteinase -1, -2 and -3 genes, which are involved in tumor invasion.
      These results suggest that ABPN may be a promising retinoid derivative offering
      not only enhanced cytotoxicity, but also increased inhibition of tumor
      invasiveness.

PMID- 14601068
TI  - Near-infrared Raman spectroscopy for optical diagnosis of lung cancer.
AB  - Raman spectroscopy is a vibrational spectroscopic technique that can be used to
      optically probe the molecular changes associated with diseased tissues. The
      objective of our study was to explore near-infrared (NIR) Raman spectroscopy for
      distinguishing tumor from normal bronchial tissue. Bronchial tissue specimens (12
      normal, 10 squamous cell carcinoma (SCC) and 6 adenocarcinoma) were obtained from
      10 patients with known or suspected malignancies of the lung. A rapid-acquisition
      dispersive-type NIR Raman spectroscopy system was used for tissue Raman studies
      at 785 nm excitation. High-quality Raman spectra in the 700-1,800 cm(-1) range
      from human bronchial tissues in vitro could be obtained within 5 sec. Raman
      spectra differed significantly between normal and malignant tumor tissue, with
      tumors showing higher percentage signals for nucleic acid, tryptophan and
      phenylalanine and lower percentage signals for phospholipids, proline and valine,
      compared to normal tissue. Raman spectral shape differences between normal and
      tumor tissue were also observed particularly in the spectral ranges of 1,000
      1,100, 1,200-1,400 and 1,500-1,700 cm(-1), which contain signals related to
      protein and lipid conformations and nucleic acid's CH stretching modes. The ratio
      of Raman intensities at 1,445 to 1,655 cm(-1) provided good differentiation
      between normal and malignant bronchial tissue (p < 0.0001). The results of this
      exploratory study indicate that NIR Raman spectroscopy provides significant
      potential for the noninvasive diagnosis of lung cancers in vivo based on the
      optic evaluation of biomolecules.

PMID- 14601069
TI  - Induced antitumor immunity against DMBA-4 metastatic mammary tumors in rats using
      laser immunotherapy.
AB  - Induced antitumor immunity is a highly effective and long-term cure for cancer,
      particularly for metastatic tumors. Laser immunotherapy was developed to induce
      such an immunologic response. It involves intratumoral administration of a light
      absorbing dye and a specially formulated immunoadjuvant, followed by noninvasive
      irradiation of a near-infrared laser. Treatment of DMBA-4 metastatic mammary
      tumors in rats with this approach has resulted in local control of primary tumors
      and eradication of untreated distant metastases. After laser immunotherapy, rats
      were resistant to tumor rechallenge and developed immunity, which could be
      adoptively transferred. To better understand the immunity induced in this tumor
      model, immunization using freeze-thaw DMBA-4 cell lysates was performed, followed
      by tumor challenge 21 days later. Tumor cell lysate immunization delayed the
      emergence of metastases but did not provide immunity against the tumor challenge.
      Also performed was surgical resection of primary tumors before the observation of
      metastatic tumors. Removal of primary tumors was unsuccessful at changing the
      course of tumor progression. Tumors re-emerged at the primary sites, and
      metastases developed at multiple remote sites. In contrast, tumor-bearing rats
      successfully treated by laser immunotherapy experienced tumor regression and
      eradication and developed strong resistance to repeated challenges by tumor cells
      of the same type. Our results show that laser immunotherapy could have potential
      for the treatment of metastatic tumors by inducing tumor-specific, long-lasting
      immunity.

PMID- 14601075
TI  - Occult "micrometastases" in ductal carcinoma in situ: investigative implications
      for sentinel lymph node biopsy.

PMID- 14601076
TI  - Combination chemotherapy for hormone-refractory prostate carcinoma: progress and
      pitfalls.

PMID- 14601077
TI  - The silence of the genes: matching mismatch repair defects with tumors.

PMID- 14601078
TI  - Gemtuzumab ozogamicin in the treatment of acute myeloid leukemia.
AB  - Gemtuzumab ozogamicin (GO) is a chemotherapeutic agent that consists of a
      humanized anti-CD33 antibody (hP67.6) linked to N-acetyl-gamma calicheamicin 1,2
      dimethyl hydrazine dichloride, a potent enediyne antitumor antibiotic. GO was
      approved conditionally by the Federal Drug Administration in May 2000 as single
      agent therapy for first recurrence of acute myeloid leukemia (AML) in a subset of
      older patients. Data on studies in AML with GO-based regimens have been reported
      rapidly in addition to new observations on the target antigen, CD33. These data
      indicate promising new areas of investigation with GO, including its application
      as maintenance therapy in patients with AML and as an induction and/or
      maintenance agent in patients with acute promyelocytic leukemia;, and they also
      have highlighted challenges in the development of GO, particularly its
      association with hepatic venoocclusive disease. In vitro data on the mechanism of
      action of GO may be particularly helpful in the design of future clinical
      studies.

PMID- 14601079
TI  - The relevance of occult axillary micrometastasis in ductal carcinoma in situ: a
      clinicopathologic study with long-term follow-up.
AB  - BACKGROUND: Ductal carcinoma in situ (DCIS) represents 20% of newly diagnosed
      breast carcinoma cases. Historically, the incidence of axillary metastasis in
      DCIS has been small (1-2%) and its significance has been debated. It is widely
      known that serial sections of lymph nodes coupled with keratin
      immunohistochemistry (IHC) increases identification of micrometastasis. The
      advent of sentinel lymph node evaluation underscores the need to reevaluate the
      significance of occult micrometastases in DCIS. METHODS: Patients with DCIS and
      negative axillary lymph nodes from 1974 to 1992 were selected from the Saint
      Barnabas Medical Center Tumor Registry. All diagnoses were confirmed, and
      paraffin blocks were retrieved after acceptance into the study. Seven serial
      sections were obtained from each block and evaluated with two cytokeratin IHC
      stains. Clinical follow-up ranged from 10 to 28 years. RESULTS: One hundred two
      patients were included in the study. Micrometastases were identified in 13
      patients (13%), mostly on 1 level and composed of microscopic clusters in the
      subcapsular sinus. Seven of these lymph node-positive patients (58%) had high
      grade comedo DCIS, 4 (33%) had intermediate grades of various types of DCIS, and
      one had a low-grade micropapillary DCIS. The overall disease recurrence rate was
      12%, but micrometasis was not detected in any of the patients who developed
      disease recurrence. CONCLUSIONS: Serial IHC evaluation of lymph nodes
      dramatically increased the identification of occult micrometastasis. However, IHC
      detected micrometastasis has no apparent clinical significance in DCIS, based on
      the current long-term clinicopathologic study. Therefore, the authors questioned
      the significance of occult micrometastasis, identified by IHC, in DCIS of any
      type and extent. Further evaluation and follow-up of lymph node micrometastases
      in patients with invasive tumors of various sizes are needed. The current
      findings would not support altering the stage of patients with DCIS and
      micrometastasis detected by IHC only.

PMID- 14601080
TI  - Gauging the impact of breast carcinoma screening in terms of tumor size and death
      rate.
AB  - BACKGROUND: While the question of whether the trials of breast cancer screening
      have resulted in a reduction in breast cancer death has been the subject of much
      scrutiny, there has been less attention to the reduction in tumor size achieved
      by screening. METHODS: Size data for invasive breast tumors were assembled from a
      variety of sources. The health consequences that can be expected from finding
      tumors of various sizes were determined using a recently developed mathematical
      method for relating tumor size to death rate. RESULTS: First, in both the Swedish
      two-country trial and at the MGH Breast Imaging Division, the sizes of the
      invasive breast cancers in the screening population (those masses seen at
      screening together with those found as palpable masses after screening
      examinations) were sufficiently smaller than the cancers found among women who
      had not used screening to have lead to considerable reductions in death. Second,
      the lack of reduction in death rates detected in both Canadian National Breast
      Screening Studies could be ascribed to the small reductions in tumor size
      achieved in these studies. Third, radiographic density had a small effect,
      whereas age had a negligible effect, on the capacity of mammographic screening to
      find breast carcinomas at smaller, and thus less lethal, sizes. CONCLUSIONS:
      Prompt attendance at annual mammographic screening offers the potential to reduce
      tumor size and, presumably, breast carcinoma death, in women of all ages and
      density groups.

PMID- 14601081
TI  - Vascular endothelial growth factor is associated with the efficacy of endocrine
      therapy in patients with advanced breast carcinoma.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) is a mediator of
      angiogenesis and is associated with a poor prognosis in patients with primary
      breast carcinoma. In the current study, the authors investigated whether there
      was an association between VEGF levels in tumor tissues and response rates to
      first-line, systemic therapy in patients with advanced breast carcinoma. METHODS:
      In 172 tumors from patients with primary breast carcinoma who developed distant
      metastases during follow-up, cytosolic levels of VEGF were measured using a
      quantitative enzyme-linked immunosorbent assay. Patients received either
      endocrine therapy (n = 96) or chemotherapy (n = 76) as first-line treatment after
      they were diagnosed with advanced disease. RESULTS: In univariate logistic
      regression analysis for response to endocrine therapy in 96 patients, an
      increasing level of VEGF, as a log-transformed, continuous variable, was
      correlated with a poor rate of response (P = 0.043). In multivariate analysis, a
      significantly lower rate of response to first-line endocrine therapy was found
      for patients who had high VEGF levels compared with patients who had low VEGF
      levels (P = 0.025). Similar results were found for the subgroup of 82 patients
      who received tamoxifen (P = 0.011). An association of VEGF with response to first
      line endocrine therapy was found in addition to a predictive impact for estrogen
      receptor/progesterone receptor status (P = 0.027). VEGF levels did not predict
      the rate of response to first-line chemotherapy. CONCLUSIONS: The results
      demonstrated that the level of VEGF affects response to endocrine therapy
      independent of steroid hormone receptor status and may help to refine further the
      indication for this treatment in individual patients. Further studies are
      warranted to explain this underlying resistance to endocrine therapy.

PMID- 14601082
TI  - The effect of tumor size and lymph node status on breast carcinoma lethality.
AB  - BACKGROUND: It has long been known that both tumor size and the presence of
      malignant disease in the regional lymph nodes are indicators of outcome for
      patients with invasive breast carcinoma; however, the way in which these two
      characteristics could be integrated into an overall assessment of prognosis has
      not been obvious. METHODS: Kaplan-Meier survival estimates (15 years) according
      to tumor size and lymph node status were obtained for women with invasive breast
      carcinoma who were observed at the University of Southern California/Van Nuys
      Breast Center (Van Nuys, California) or at Massachusetts General Hospital
      (Boston, Massachusetts). RESULTS: To isolate the individual contributions to
      death made by tumor size and lymph node status, data were sorted according to
      both of these variables. For women with tumors of equivalent size, lethality
      increased with increasing number of positive lymph nodes, such that there was an
      extra approximately 6% chance of death associated with each positive lymph node.
      For women with equivalent lymph node status, tumor size was associated with
      increased lethality, such that each millimeter of tumor diameter was associated
      with an additional approximately 1% chance of death. The overall lethality was
      equal to the sum of the contribution from lymph node status and the contribution
      from tumor size, and this finding led to the creation of a new technique (the
      Size+Nodes method) for predicting outcome. CONCLUSIONS: The Size+Nodes method was
      shown to be capable of accurately estimating the risk of death due to invasive
      breast carcinoma from information on the size of the primary tumor and the number
      of positive lymph nodes. In addition, this method was used to stratify women into
      groups according to breast carcinoma lethality. In contrast, classification of
      women according to lymph node positivity, T status, or disease stage created
      groups with wide and overlapping levels of lethality.

PMID- 14601083
TI  - Prognosis after regional lymph node recurrence in patients with stage I-II breast
      carcinoma treated with breast conservation therapy.
AB  - BACKGROUND: The authors evaluated the risk factors for regional lymph node
      recurrence and the prognosis of patients with regional nodal recurrence after
      breast conservation therapy for Stage I-II breast carcinoma. METHODS: Between
      1977 and 1995, 1293 women with pathologic Stage I and II (T1-2, N0-1) breast
      carcinoma were treated with breast-conserving therapy including lumpectomy,
      axillary lymph node dissection, and definitive breast irradiation. A total of 39
      women (3%) had any regional lymph node recurrence. The median follow-up was 8.5
      years (range, 1.5-24 years). RESULTS: Among 39 patients with a regional lymph
      node recurrence, 10 women had regional recurrence only, 16 had simultaneous
      locoregional recurrence, and 13 had simultaneous regional and distant recurrence.
      Regional recurrence occurred in the axillary lymph nodes only (n = 21; 51%),
      supraclavicular lymph nodes only (n = 8; 23%), internal mammary lymph nodes only
      (n = 3; 8%), infraclavicular lymph nodes only (n = 3; 8%), or multiple lymph node
      sites (n = 4; 10%). The median time to regional lymph node recurrence was 3.1
      years (range, 0.2-20.9 years). Overall survival after regional-only disease
      recurrence was 44%, locoregional disease recurrence was 26%, and regional with
      distant disease recurrence was 12%. Cause-specific survival rates at 10 years for
      the 3 groups were 44%, 40%, and 12%, respectively. For patients who presented
      with simultaneous regional and distant metastases, the median survival period was
      1.1 years, compared with 5.2 years for women who developed distant disease
      subsequent to regional recurrence. CONCLUSIONS: Regional lymph node recurrence
      after breast conservation therapy may be salvaged, but is associated with a high
      rate of either simultaneous or subsequent distant metastatic dissemination and
      poor overall prognosis.

PMID- 14601084
TI  - Reoperations after prophylactic mastectomy with or without implant
      reconstruction.
AB  - BACKGROUND: The authors characterized the unanticipated reoperations after
      prophylactic mastectomy, with or without implant reconstruction. METHODS: The
      surgical cohort was comprised of 1417 women with a family history of breast
      carcinoma. The women received a prophylactic mastectomy with (bilateral, n = 593;
      contralateral, n = 506) or without reconstruction (n = 318) at the Mayo Clinic
      (Rochester, MN) between 1960 and 1993. Reoperations and indications for
      reoperation were compiled from medical records and a patient survey. RESULTS:
      Three hundred eighteen women received a bilateral (n = 39) or contralateral (n =
      279) prophylactic mastectomy without reconstruction. With a median follow-up of
      15 years, 18 women (6%) required reoperation. Most of these reoperations occurred
      within the first year after prophylactic mastectomy. Five hundred ninety-three
      women had reconstruction with implants following bilateral prophylactic
      mastectomy. Approximately one-half of the women (52%) required at least 1
      unanticipated reoperation during a median follow-up of 14 years. Approximately
      39% of all reoperations occurred within 1 year of breast reconstruction and 69%
      within 5 years. Implant-related issues were the most common cause for
      reoperation. Some women with breast carcinoma elected to receive contralateral
      prophylactic mastectomy with therapeutic mastectomy for the affected breast. Five
      hundred six women received reconstruction with implants. During a median follow
      up of 8.8 years, 189 women (37%) required unanticipated reoperation. The most
      common indication was implant-related issues. The time course of reoperations was
      similar to that for women in the bilateral group. CONCLUSIONS: Surgical
      reoperations were fairly common among women who received prophylactic mastectomy
      with implant reconstruction. Most of the reoperations were implant related.
      Reoperations were fairly uncommon after prophylactic mastectomy without
      reconstruction.

PMID- 14601085
TI  - Lifetime recreational exercise activity and risk of breast carcinoma in situ.
AB  - BACKGROUND: The incidence rates of breast carcinoma in situ (BCIS) have increased
      dramatically over the past two decades, primarily because of increased
      mammography screening. Ductal carcinoma in situ, which accounts for approximately
      85% of BCIS and 10-20% of all breast carcinomas, is generally recognized as the
      final step in the progression to invasive disease. To the authors' knowledge, few
      studies have been conducted to date to evaluate BCIS risk factors. Because of its
      potential effects on circulating sex hormones, physical activity has been
      proposed as a modifiable risk factor for invasive breast carcinoma. However, the
      relation to BCIS risk is poorly understood. METHODS: The authors analyzed data
      from a population-based case-control study conducted in Los Angeles County.
      Personal interviews were conducted with 567 white and black women (age range, 35
      64 years) who had been newly diagnosed with BCIS between March 1, 1995 and May
      31, 1998 and with 1026 control subjects, of whom 616 were screened within 2 years
      of identification. RESULTS: After excluding unscreened control subjects (n = 410)
      and adjusting for potential confounding factors, the risk of BCIS was
      approximately 35% lower among women with any exercise activity compared with
      inactive women, although no significant trend was observed. The association
      between exercise activity and the risk of BCIS was modified by a family history
      of breast carcinoma. No reduction in risk was observed among women reporting a
      first-degree family history of breast carcinoma (homogeneity of trends P value =
      0.02). CONCLUSIONS: The findings of the current study suggest that exercise
      activity may modify the risk of BCIS, particularly among women without a family
      history of breast carcinoma.

PMID- 14601086
TI  - Ductal lavage in patients undergoing mastectomy for mammary carcinoma: a
      correlative study.
AB  - BACKGROUND: Ductal lavage (DL) is a new method for the sampling of breast
      epithelium. Data regarding its sensitivity in the detection of epithelial
      abnormalities, including carcinoma in situ (CIS), remains limited. METHODS: DL
      was performed in the affected breasts of 26 women undergoing mastectomy for
      mammary carcinoma and in the clinically normal breast of 4 additional women
      undergoing risk-reducing mastectomy. After surgery, dye was injected through the
      microcatheter used for DL. Three cytopathologists independently reviewed all DL
      slides and the data reflect consensus by at least two reviewers. Interobserver
      agreement was assessed. The findings in DL samples were correlated with the
      features of CIS in the mastectomy specimens. RESULTS: Four (14%) of 29 DL samples
      satisfactory for evaluation showed marked atypia, 10 (34%) showed mild atypia,
      and 15 (52%) were benign. No DL sample was clearly malignant. Interobserver
      agreement was good (average kappa = 0.52). Of the DL samples satisfactory for
      evaluation, 27 had been obtained from 24 breasts containing CIS, which included
      18 ductal CIS (DCIS), 3 lobular CIS (LCIS), 2 DCIS and LCIS, and 1 solid CIS with
      mixed ductal and lobular features. Invasive carcinoma was present in 20 samples.
      Two DL samples from breasts with extensive LCIS showed mild atypia and injected
      dye was identified in ducts and lobules involved by LCIS. CONCLUSIONS: DL had low
      sensitivity for CIS in breasts that also contained invasive carcinoma. The use of
      DL remains investigational, and close follow-up should be continued for all
      patients undergoing DL, including those with benign diagnoses.

PMID- 14601087
TI  - Concurrent cisplatin, paclitaxel, and radiotherapy as preoperative treatment for
      patients with locoregional esophageal carcinoma.
AB  - BACKGROUND: A Phase II trial was conducted at the University of Michigan to
      determine the efficacy of a preoperative regimen of concurrent cisplatin,
      paclitaxel, and radiation for patients with locoregional esophageal carcinoma.
      METHODS: Sixty-nine patients with esophageal carcinoma were treated with
      cisplatin 75 mg/m(2) on Day 1, paclitaxel 60 mg/m(2) on Days 1, 8, 15, and 22,
      and radiation 1.5 Gray (Gy) twice per day on Days 1-5, 8-12, and 15-19, for a
      total dose of 45 Gy. Transhiatal esophagectomy was performed on approximately Day
      50. RESULTS: The treatment regimen was well tolerated. Only 13% of patients
      developed Grade 3 or 4 neutropenia and 17% of patients required feeding tubes.
      Ninety percent of all patients had complete tumor resection at the time of
      surgery. Nineteen percent of patients achieved a complete histologic response in
      the resected specimen. The median survival period was 24 months. One-, 2-, and 3
      year survival probabilities were 75%, 50%, and 34%, respectively. CONCLUSIONS:
      This cisplatin-based preoperative regimen, which contained paclitaxel rather than
      5-fluorouracil, was well tolerated. The survival data compared favorably with
      other previously reported combinations. This regimen is a reasonable preoperative
      approach for patients with localized esophageal carcinoma.

PMID- 14601088
TI  - Decreased abundance of trefoil factor 1 transcript in the majority of gastric
      carcinomas.
AB  - BACKGROUND: Gastric carcinoma is one of the leading causes of cancer-related
      death worldwide, but the mechanisms underlying its development and progression
      still remain largely uncharacterized. As loss of trefoil factor 1 (TFF1)
      expression leads to neoplastic growth in the antropyloric mucosa of mice, the
      authors sought to comprehensively study the human TFF1 gene in primary gastric
      carcinomas. METHODS: The authors studied the human TFF1 gene in primary gastric
      carcinomas and normal gastric mucosa at the DNA, RNA, and protein levels through
      DNA sequencing, quantitative real-time reverse transcriptase-polymerase chain
      reaction, and immunohistochemistry. RESULTS: Strikingly, TFF1 mRNA expression was
      significantly decreased in all 37 gastric carcinomas studied compared with normal
      gastric mucosa. Furthermore, six tumor/normal pairs with available histologic
      samples demonstrated a marked decrease in protein expression in tumor samples.
      Screening of the entire TFF1 coding region in a panel of 42 human gastric tumors
      did not reveal any somatic mutations, although a few rare germline sequence
      variants were identified. CONCLUSIONS: These findings demonstrated a significant
      decrease in the TFF1 transcript in the majority of human gastric carcinomas along
      with a corresponding reduction in protein expression, both of which occurred in
      the absence of gene mutation. Dysregulation of TFF1 expression at the transcript
      level was a critical event in the development of most gastric carcinomas.

PMID- 14601089
TI  - Weekly paclitaxel, estramustine phosphate, and oral etoposide in the treatment of
      hormone-refractory prostate carcinoma: results of a Minnie Pearl Cancer Research
      Network phase II trial.
AB  - BACKGROUND: The objective of the current study was to evaluate the efficacy and
      toxicity of weekly paclitaxel, oral etoposide, and estramustine phosphate in the
      treatment of patients with advanced, hormone-refractory prostate carcinoma.
      METHODS: Patients with hormone-refractory prostate carcinoma who had received no
      more than one previous chemotherapy regimen were eligible for this trial. Forty
      two patients were treated between February 1998 and March 2000. Toxicity was
      excessive in the first 3 patients treated (Grade 3-4 leukopenia, 3 patients;
      death due to sepsis, 1 patient); the remaining 39 patients received lower doses
      of etoposide and estramustine phosphate (paclitaxel 50 mg/m(2) as a 1-hour,
      intravenous infusion on Days 1, 8, 15; etoposide 50 mg orally twice daily on Days
      1-10; and estramustine phosphate 280 mg orally 3 times daily on Days 1-10).
      Courses were repeated every 28 days. Patients were evaluated for objective and/or
      serologic response after two courses of treatment; responding patients continued
      treatment for six courses. RESULTS: Fourteen of 40 evaluable patients (35%) had
      either an objective response or a serologic response to treatment. The median
      survival for the entire group was 9.5 months, with 1-year, 2-year, and 3-year
      survival rates of 38%, 12%, and 10%, respectively. Neutropenia was the most
      common Grade 3-4 toxicity and occurred in 38% of patients (11% of courses).
      Thirteen patients (33%) had severe fatigue, and 2 patients had treatment-related
      deaths due to sepsis. CONCLUSIONS: Although the three-drug combination had
      activity in patients with hormone-refractory prostate carcinoma, the results did
      not appear any better than the results achieved with less toxic
      taxane/estramustine phosphate combinations. Further development of this three
      drug regimen is not recommended.

PMID- 14601090
TI  - Mismatch repair gene expression defects contribute to microsatellite instability
      in ovarian carcinoma.
AB  - BACKGROUND: hMLH1, the human MutL homologue, has been linked to microsatellite
      instability (MSI) in gastrointestinal tumors. However, to the authors' knowledge,
      the role of hMLH1, the other mismatch repair genes (MMR), and MSI in ovarian
      carcinoma has not been well defined. The purpose of the current study was to
      determine the relation between MSI of ovarian carcinoma and MMR gene expression,
      hMLH1 and hMSH2 hypermethylation, and hMLH1 and hMSH2 null mutations. METHODS:
      hMLH1 mRNA was detected by reverse transcriptase-polymerase chain reaction (RT
      PCR) and amplification of cDNA using a housekeeping gene (glycerol 3-phosphate
      dehydrogenase) as a control for mRNA quality and quantity. Methylation-specific
      PCR (MS-PCR) was used to correlate methylation of the hMLH1 and hMSH2 CpG islands
      with mRNA expression status. Similar techniques were used to evaluate the
      concomitant expression of five other MMR: hMSH2, hMSH3, hMSH6, PMS1, and PMS2.
      Microsatellite instability was studied using the National Cancer Institute
      consensus markers (D2S123, D5S346, D17S250, BAT25, and BAT26) and NM23 as
      described previously. RESULTS: One hundred twenty-five primary tumors were
      analyzed. High-frequency MSI (MSI-H) was found in 21 tumors (16.8%). hMLH1 mRNA
      was absent in 10 of these 21 tumors (47.6%). In each case, coordinated
      hypermethylation of both regions A and C of the promoter was identified.
      Microsatellite stable and low-frequency MSI tumors all were found to express not
      only hMLH1 but the other MMR genes as well (P < 0.001). Absence of expression of
      hMSH2 and the four other MMRs occurred in tumors with absent hMLH1 mRNA
      expression because of CpG island hypermethylation. No absence of expression of
      hMSH2, hMSH3, hMSH6, PMS1, or PMS2 was found to occur in tumors expressing hMLH1.
      None of the 11 MSI-H tumors without promoter hypermethylation demonstrated a null
      mutation in hMLH1 or hMSH2. CONCLUSIONS: A molecular mechanism to explain > 50%
      of the MSI-H phenotype in ovarian carcinoma cases was demonstrated. MSI-H may
      occur because of MMR defects, especially hMLH1 promoter hypermethylation.
      Additional mechanisms are required to explain the balance between the cases of
      MSI-H as well as the phenomenon of MSI-L tumors.

PMID- 14601091
TI  - Expression of steroid receptor coactivators and corepressors in human endometrial
      hyperplasia and carcinoma with relevance to steroid receptors and Ki-67
      expression.
AB  - BACKGROUND: To examine the steroid hormone dependent growth mechanism of human
      endometrial hyperplasia and carcinoma, expression levels of steroid receptor
      cofactors, such as coactivators (steroid receptor coactivator 1 [SRC-1] and
      p300/cyclic AMP-response element-binding protein (p300/CBP]) and corepressors
      (nuclear receptor corepressor [NCoR] and silencing mediator for retinoid and
      thyroid-hormone receptors [SMRT]), were investigated. METHODS: The expression
      levels of cofactors were examined immunohistochemically using 20 samples of
      normal endometria, 36 samples of hyperplastic endometria, and 58 of malignant
      endometria and were compared with the expression levels of estrogen receptor
      (ER), progesterone receptor (PR), and a proliferation marker, Ki-67. RESULTS: In
      samples of normal endometria, the expression of coactivators was observed
      diffusely in glandular cells in the proliferative phase, with a mean positivity
      index (PI) of 81.8 for SRC-1 and 91.3 for p300/CBP, whereas expression levels
      decreased in endometrial hyperplasia (PI: SRC-1, 58.9; p300/CBP, 83.8) and
      endometrial carcinoma (PI: SRC-1, 45.0; p300/CBP, 55.4). In endometrial
      hyperplasia, there was a significant correlation between the expression of ER and
      SRC-1 or p300/CBP. In contrast, there were no significant statistical or
      topologic correlations between the expression of coactivators and the expression
      of ER/PR in endometrial carcinoma. The expression of corepressors generally was
      limited, except for elevated expression of NCoR in endometrial hyperplasia (PI,
      23.8). CONCLUSIONS: The current study showed that expression levels of the
      steroid receptor coactivators SRC-1 and p300/CBP were reduced in endometrial
      carcinoma compared with normal and hyperplastic endometrium. In addition,
      topologic coexpression of both coactivators and ER/PR was lost in endometrial
      carcinoma. Accordingly, limited response to sex steroids in patients with
      endometrial carcinoma may be ascribed to the dissociation of cofactors and ER/PR.

PMID- 14601092
TI  - Intraarterial cisplatin with intravenous paclitaxel and ifosfamide as an organ
      preservation approach in patients with paranasal sinus carcinoma.
AB  - BACKGROUND: The objectives of this study were to determine the efficacy, organ
      preservation rate, and safety of intraarterial (IA) cisplatin in combination with
      intravenous paclitaxel and ifosfamide in patients with locally advanced carcinoma
      of the paranasal sinuses who required orbital exenteration or major craniofacial
      resection for complete tumor resection. METHODS: Patients were treated with
      intravenous paclitaxel (135 mg/m(2)) on Day 1, ifosfamide (1000 mg/m(2)) on Days
      1-3, sodium mercaptoethanesulfonate (600 mg/m(2)) on Days 1-3, and IA cisplatin
      (100 mg/m(2)) on Day 1 every 21 days. RESULTS: Of 24 study participants, 20
      patients received at least 1 course of IA cisplatin, 1 patient had an early
      death, and 19 patients were evaluable for response. Five of those 19 patients
      (26%) achieved a complete response (CR), 6 patients (32%) achieved a partial
      response, and 8 patients (42%) had stable disease or developed progressive
      disease. Eye-sparing surgery followed by radiotherapy (RT) was feasible in 7 of
      24 patients, RT was offered to only 7 patients, whereas 3 patients received
      chemotherapy and RT, 2 patients refused further therapy, 3 patients underwent
      craniofacial resection with orbitectomy, and 1 patient was treated systemically
      for metastatic disease. At the completion of treatment, 14 of 23 patients (61%)
      with locally advanced disease were disease free, and the orbit was preserved in
      21 of 24 patients (88%). The overall survival, progression-free survival, and
      disease-free survival rates at 2 years were 60%, 50%, and 84%, respectively.
      Toxicity was substantial, with two patients experiencing cerebrovascular ischemia
      (one transient and one cerebrovascular accident) and three patients experiencing
      cranial neuropathy, which was reversible in two patients. CONCLUSIONS: Despite
      the encouraging organ-preservation rate, the approach studied resulted in
      substantial toxicity, and more effective adjunctive therapy is needed.
      Alternative approaches, including the integration of targeted therapy agents in
      induction chemotherapy regimens followed by concomitant chemotherapy and RT or
      eye-sparing surgery, need further exploration.

PMID- 14601093
TI  - Definitive radiotherapy alone or combined with a planned neck dissection for
      squamous cell carcinoma of the pharyngeal wall.
AB  - BACKGROUND: In the current study,the authors analyzed the results of definitive
      radiotherapy for squamous cell carcinoma of the pharyngeal wall. METHODS: Between
      1964 and 2000, 148 patients were treated with definitive radiotherapy. All
      patients had a 2-year minimum follow-up. RESULTS: The following 5-year rates of
      local and ultimate local control were obtained: T1 disease, 93% and 93%; T2
      disease, 82% and 87%; T3 disease, 59% and 61%; and T4 disease, 50% and 50%,
      respectively. Multivariate analysis revealed that twice-daily fractionation (P =
      0.0009), American Joint Committee on Cancer Stage I-II disease (P = 0.0051), and
      oropharyngeal primary site (P = 0.0193) were associated with improved
      locoregional control. The following 5-year absolute and cause-specific survival
      rates were obtained: Stage I, 56% and 89%; Stage II, 52% and 88%; Stage III, 24%
      and 44%; Stage IV, 22% and 34%; and overall, 30% and 49%, respectively. Eight
      patients (5%) died of complications. CONCLUSIONS: Locoregional control and
      survival were found to be related to site, extent of disease, and fractionation
      schedule. Although outcomes have improved in recent years, the morbidity of
      treatment was significant in the current study and a substantial proportion of
      patients died secondary to the malignancy.

PMID- 14601094
TI  - Clear cell ependymoma: a clinicopathologic and radiographic analysis of 10
      patients.
AB  - BACKGROUND: Clear cell ependymoma (CCE) is an uncommon central nervous system
      tumor with a predilection for the supratentorial region in children.
      Histologically, it may mimic oligodendroglioma, central neurocytoma,
      hemangioblastoma, and renal cell carcinoma. METHODS: The authors reviewed the
      clinical, radiographic, and pathologic features, therapy, and outcome in 10
      children with CCE who were treated at St. Jude Children's Research Hospital (1984
      2003). Fluorescence in situ hybridization (FISH) was performed using 1p/1q,
      19p/19q, CEP18/DAL1, and bcr/NF2 probe pairs. RESULTS: The median patient age at
      diagnosis was 7.5 years (range, 1-19 years). Tumors occurred supratentorially in
      9 of 10 patients. All tumors had rounded nuclei with surrounding, clear halos and
      at least focal perivascular pseudorosettes. Seven tumors had anaplastic features.
      No deletions involving 1p, 19q, or NF2 were detected. The tumors from 5 of 7
      patients, all with anaplasia, had losses of both CEP18 and DAL-1.
      Radiographically, all tumors were enhanced, and 9 tumors had associated cysts
      with enhancing walls. Seven patients underwent gross total resection, which was
      near total in one patient and subtotal in two patients. Five patients received
      immediate postoperative local radiotherapy. Three patients were diagnosed
      initially with pilocytic astrocytoma (one patient) and oligodendroglioma (two
      patients) and were observed. The progression-free survival and overall survival
      rates at 5 years were 34% +/- 20% and 75% +/- 19%, respectively. The median
      follow-up was 37 months (range, 5-239 months). Five patients developed local
      recurrence within a median of 9 months after diagnosis. Two patients developed
      extracranial soft tissue and lymph node metastases. CONCLUSIONS: CCEs were found
      to have a predilection for extraneural metastases and early recurrence and
      demonstrate characteristic radiographic features, anaplastic histologic features,
      and chromosome 18 losses. The authors recommend resection followed by local
      radiotherapy as the treatment of choice in children.

PMID- 14601095
TI  - Single nucleotide polymorphism in fibroblast growth factor receptor 4 at codon
      388 is associated with prognosis in high-grade soft tissue sarcoma.
AB  - BACKGROUND: A recent study revealed that single nucleotide polymorphism (SNP) at
      codon 388 (Gly or Arg) of fibroblast growth factor receptor 4 (FGFR4) was
      associated with prognosis in patients with carcinoma of the breast and colorectal
      carcinoma. The purpose of the current study was to investigate the correlation
      between codon 388 SNP and clinical prognosis in patients with sarcoma of the bone
      and soft tissues. METHODS: Tumor samples were obtained from 143 patients with
      high-grade bone and soft tissue sarcomas at Okayama University Hospital between
      1986-2002, and from 102 healthy volunteers. SNP of codon 388 was detected by
      sequencing and fragment length of polymerase chain reaction products digested by
      restriction enzyme. The chi-square test was used to compare genotype distribution
      and the Kaplan-Meier method was used for survival analysis. RESULTS: With regard
      to FGFR4 genotypes in the 143 patients studied, 54 (37.8%) were Gly/Gly, 72
      (50.3%) were Gly/Arg, and 17 (11.9%) were Arg/Arg, findings that were not
      significantly different from those of controls (P = 0.97). With regard to
      cumulative overall and metastasis-free survival, patients with the Gly/Gly
      genotype were found to have a better prognosis (P = 0.085 and P = 0.27,
      respectively). FGFR4 SNP was found to be correlated significantly with overall
      and metastasis-free survival in patients with soft tissue sarcomas (P = 0.029 and
      P = 0.045, respectively), but not in those patients with bone sarcomas (P = 0.88
      and P = 0.75, respectively). CONCLUSIONS: In the current study, the authors found
      a significant correlation between FGFR4 SNP and prognosis in patients with soft
      tissue sarcoma, although the samples were comprised of various histologic types.
      This SNP might be used to improve the prediction of clinical prognosis and lead
      to new treatment strategies in patients with soft tissue sarcomas.

PMID- 14601096
TI  - Antiangiogenetic therapy with pioglitazone, rofecoxib, and metronomic
      trofosfamide in patients with advanced malignant vascular tumors.
AB  - BACKGROUND: Systemic therapy options for patients with advanced angiosarcomas are
      limited, and their prognosis is poor. The idea of angiostatic therapy following
      the paradigm of metronomic dosed chemotherapeutics combined with proapoptotic
      biomodulators had not been considered previously in these patients. Therefore, in
      a pilot study, the efficacy of metronomically scheduled, low-dose trofosfamide in
      combination with the peroxisome proliferator-activated receptor gamma agonist,
      pioglitazone, and the selective cyclooxygenase-2 inhibitor, rofecoxib, was
      evaluated in patients with advanced vascular malignancies. METHODS: Six patients
      with advanced and pretreated but progressive, malignant vascular tumors (5
      angiosarcomas and 1 hemangioendothelioma) received a combination of pioglitazone
      (45 mg per day orally) plus rofecoxib (25 mg per day orally) and, after 14 days,
      trofosfamide (3 x 50 mg per day orally). The therapy was administered
      continuously until progression was observed. If necessary, doses were modified
      according to side effects. RESULTS: Two patients responded with complete
      remission of disease, one patient responded with partial remission, and three
      patients achieved stabilization of disease (no change). The median progression
      free survival was 7.7 months (range, 2-15 months). Side effects generally were
      mild (World Health Organization Grade 1-2). Hospitalization was not necessary.
      CONCLUSIONS: This new triple combination of low-dose metronomic trofosfamide,
      pioglitazone, and rofecoxib may represent a feasible new alternative in the
      palliative treatment of patients with advanced malignant vascular tumors.

PMID- 14601097
TI  - Detection of recurrent oral squamous cell carcinoma by [18F]-2-fluorodeoxyglucose
      positron emission tomography: implications for prognosis and patient management.
AB  - BACKGROUND: Patients with recurrent oral squamous cell carcinoma (OSCC) have a
      dismal prognosis and represent a therapeutic challenge. A positron emission
      tomography (PET) scan with [(18)F]-2-fluorodeoxyglucose ([(18)F]FDG) can improve
      early cancer detection. The current study evaluates the prognostic value of
      [(18)F]FDG-PET scan in patients with recurrent OSCC. METHODS: The authors studied
      97 patients with previously resected OSCC who were restaged by PET scanning. Of
      the 97 patients, 64 had no evidence of clinical disease and 33 were suspected of
      having disease by imaging, clinical findings, or pathologic evaluation. The
      median follow-up period was 35.4 months after a PET scan. The end points included
      disease recurrence, a disease recurrence-free period 6 months after a PET scan,
      or death. RESULTS: The overall sensitivity of a PET scan did not exceed 90% and
      its specificity varied from 67% for local disease recurrence/second primaries to
      99% for lymph node metastasis. Increased [(18)F]FDG uptake predicted increased
      hazard of death (hazard ratio: 6.83; P = 0.00034) and proved to be a highly
      predictive marker of disease status. A significant association was established
      for incremental standardized uptake values and 3-year patient survival
      (P=0.0089), indicating that intense glucose metabolism in the tumor is a negative
      marker of survival in recurrent OSCC. Overall, survival was longer in patients
      with a negative rather than a positive PET scan (P < 0.00001). CONCLUSIONS: PET
      scanning was found to be highly valuable for diagnosing OSCC recurrence in a
      postoperative setting. It provided prognostic information and played an important
      role in patient counseling and management.

PMID- 14601098
TI  - The surgical treatment of cancer: a comparison of resource utilization following
      procedures performed with a curative and palliative intent.
AB  - BACKGROUND: Costs associated with the provision of medical care continue to
      escalate. Therefore, providers must evaluate the cost-effectiveness and benefit
      to individual healthcare practices. The authors evaluated the immediate and short
      term resource utilization needs of patients undergoing surgical intervention with
      curative or palliative intent. METHODS: Three hundred two patients undergoing
      surgery with therapeutic intent were observed from the time of admission for
      intervention until the time of death or until 6 months from the time of the
      surgical procedure. Surgeons preoperatively identified each case as either
      curative or palliative in intent. Demographic information, as well as the nature
      of all interactions with the cancer center, was recorded. RESULTS: Surgeons
      identified 58 (19%) procedures as palliative and 244 (81%) as curative in intent.
      Demographic characteristics between the two groups were similar, although
      recurrent or metastatic disease was more often present in palliative rather than
      curative patients (P = 0.0078) and palliative intent patients were more likely to
      have received previous therapy. During the 6-month period, 4690 encounters
      occurred with the cancer center. The mean number of encounters per patient in
      each group was similar, although curative intent patients were more likely to
      have visits with therapeutic intent including chemotherapy administration (P =
      0.01), radiation (P = 0.003), or repeat surgical procedures (P = 0.006). In
      contrast, palliative patients were more likely to be admitted for management of
      symptoms (P = 0.0001) and had fewer hospital-free days than did curative patients
      (P = 0.0069). CONCLUSIONS: The average number of encounters for patients
      undergoing treatment of disease was not significantly different, suggesting that
      patients undergoing surgery with palliative intent do not require a greater
      amount of resources than curative intent patients. The nature of the
      interactions, however, was different, suggesting that resource needs are
      different and may need to be anticipated in the assessment of how better quality
      outcomes can be achieved in the palliative surgery setting.

PMID- 14601099
TI  - Revision of the International Neuroblastoma Pathology Classification:
      confirmation of favorable and unfavorable prognostic subsets in
      ganglioneuroblastoma, nodular.
AB  - BACKGROUND: Ganglioneuroblastoma, nodular (GNBn) comprises one of the categories
      of peripheral neuroblastic tumors. All tumors in this category, according to the
      original International Neuroblastoma Pathology Classification, are classified
      into an unfavorable histology group. Subsequently, it has been reported that GNBn
      can be divided into two prognostic subsets, a favorable subset (FS) and an
      unfavorable subset (US). METHODS: Histology slides from 70 patients who were
      enrolled in Children's Cancer Group studies 3881 and 3891 and who had a diagnosis
      of GNBn were reviewed jointly by the members of International Neuroblastoma
      Pathology Committee (INPC): 1) to confirm the diagnosis of GNBn, 2) to identify
      the FS and US by applying the same age-linked criteria that were used to
      distinguish the favorable histology group and unfavorable histology group in
      conventional neuroblastoma tumors from the neuroblastomatous component of GNBn
      tumors, and 3) to verify the significant prognostic difference between these two
      subsets. The patients had been used in a previous study, and survival data for
      the patients were updated since the time of their last report. RESULTS: The
      review clarified and illustrated morphologic characteristics of classical GNBn
      and it variants. The diagnosis of GNBn was confirmed in 67 of 70 patients. There
      were 22 patients with GNBn in the FS and 45 patients with GNBn in the US. The
      estimated survival differences between the FS and US patients with GNBn were
      statistically significant (8-year event free survival rate: 86.1% vs. 32.2%; P =
      0.0003; overall survival rate: 90.5% vs. 33.2%; P = 0.0003). CONCLUSIONS: This
      study confirmed the recently defined prognostic subsets of GNBn. The INPC
      proposes to modify the International Neuroblastoma Pathology Classification by
      distinguishing the FS and the US among patients with GNBn tumors.

PMID- 14601100
TI  - Outcome in 34 patients with juvenile-onset mycosis fungoides: a clinical,
      immunophenotypic, and molecular study.
AB  - BACKGROUND: Mycosis fungoides (MF) is predominantly a disease of older patients,
      but occasionally occurs in children. The aims of the current study were to
      describe the clinical presentation, pathologic features, and disease progression
      (DP) in patients who developed MF before age 16 years. METHODS: A retrospective
      study was performed. Patients with juvenile-onset MF were identified from our
      databases. Clinical features were determined from the medical records and patient
      interviews. Histologic, immunohistochemical, and T-cell receptor (TCR) gene
      analysis was performed. RESULTS: Thirty-four patients were identified: 50% had
      Stage IA disease, 47% had Stage IB disease, and 3% had Stage IIA disease. The
      male-to-female ratio was 2:1. Clinical features included hypopigmented lesions
      (24%), poikiloderma (26%), pilotropic disease (9%), and disease associated with
      lymphomatoid papulosis (18%). Twenty-eight patients had diagnostic histology, and
      six patients were included on the basis of compatible histology and a TCR clone
      in lesional skin. A cytotoxic immunophenotype was observed in 38%, including 71%
      of patients with hypopigmented lesions. Overall disease-specific survival (DSS)
      rates at 5 and 10 years were 95% and 93%, respectively. DP rates were 5% at 5
      years and 29% at 10 years. Subgroup analysis demonstrated improved DSS and
      reduced DP in patients with Stage IA disease, those with hypopigmented or
      poikilodermatous lesions, and those with associated lymphomatoid papulosis.
      CONCLUSIONS: The prognosis for juvenile-onset MF is similar to that of adult
      onset disease. There was an overrepresentation of a cytotoxic phenotype, which
      was most marked in hypopigmented variants. Widespread cutaneous disease (Stage
      IB) indicated a less favorable outcome.

PMID- 14601101
TI  - Monitoring of circulating angiogenic factors in dendritic cell-based cancer
      immunotherapy.
AB  - BACKGROUND: A promising treatment approach for patients with malignant disease
      that recently has found its way into clinical trials is based on vaccination with
      autologous dendritic cells loaded with tumor antigens. However, adequate assays
      for monitoring clinical and immunologic responses still are under debate. In
      recent years, the determination of angiogenic markers has shown considerable
      potential in the diagnosis and prognosis of patients with malignant disease,
      because tumor growth and spread are promoted by angiogenesis, the formation of
      new blood vessels. METHODS: The authors established a method for measuring the
      plasma levels of three modulators of angiogenesis: vascular endothelial growth
      factor, platelet-derived endothelial cell growth factor, and thrombospondin-1.
      The angiogenic blood profile of a healthy control group was characterized and
      compared with a group of patients with malignant disease. Ultimately, levels of
      circulating angiogenic factors were monitored in the course of dendritic cell
      based cancer immunotherapy. RESULTS: Baseline levels of angiogenic mediators
      varied substantially among healthy individuals but showed consistent values for
      each individual. Blood levels of circulating angiogenic factors were elevated
      significantly in patients with advanced disease and were highly sensitive to
      dendritic cell-based immunotherapy. CONCLUSIONS: To our knowledge, the current
      report was the first to analyze circulating levels of angiogenic factors during
      dendritic cell-based immunotherapy. The authors observed a noteworthy change in
      the angiogenic blood profile with treatment, and this change was correlated with
      the induction of an immunologic response.

PMID- 14601102
TI  - Perceptions and attitudes of clinical oncologists on complementary and
      alternative medicine: a nationwide survey in Japan.

PMID- 14601104
TI  - Percutaneous radiofrequency ablation of liver metastases in potential candidates
      for resection: the "test-of-time" approach.

PMID- 14601129
TI  - Efficient gene transfer of a simian immuno-deficiency viral vector into
      cardiomyocytes derived from primate embryonic stem cells.
AB  - BACKGROUND: Embryonic stem (ES) cells continually proliferate and can generate
      large numbers of differentiated cells. Genetic manipulation of transplantable
      cells derived from primate ES cells offers considerable potential for development
      research and regenerative cell therapy. However, protocols for efficient gene
      transfer into primate ES-cell-derived cells have not yet been established.
      METHODS: Spontaneously contracting areas were derived from cynomolgus monkey ES
      cells. Features of cardiomyocytes in the area were analyzed according to gene
      expression (RT-PCR), morphology (immunostaining and electron microscopy), and
      function (intracellular calcium transience). Beating cells were transduced using
      a simian immunodeficiency virus (SIV) vector expressing enhanced green
      fluorescence protein (EGFP), then transplanted into ischemic rat myocardium.
      RESULTS: Beating cells derived from monkey ES cells displayed gene expression,
      ultrastructural and functional properties of early-stage cardiomyocytes. Highly
      efficient (97% cardiac phenotype) and stable transduction of these ES-cell
      derived cardiomyocytes was achieved using SIV vector without altering contractile
      function. In addition, transduced cardiomyocytes survived in the myocardium of a
      rat myocardial infarction model. CONCLUSIONS: A lentiviral vector system based on
      SIV represents a useful vehicle for genetic modification of cardiomyocytes
      derived from primate ES cells, and can extend the application of primate ES cells
      to gene therapy.

PMID- 14601130
TI  - A soluble CAR-SCF fusion protein improves adenoviral vector-mediated gene
      transfer to c-Kit-positive hematopoietic cells.
AB  - BACKGROUND: Although adenoviral vectors primarily derived from the adenovirus
      serotype 5 (Ad5) are widely used for many gene transfer applications, they cannot
      efficiently infect hematopoietic cells, since these cells do not express the
      coxsackie-adenoviral receptor (CAR). METHODS: We have developed a soluble fusion
      protein that bridges adenoviral fibers and the c-Kit receptor to alter Ad5
      tropism to immature hematopoietic cells. The CAR-SCF fusion protein consists of
      the extracellular domains of CAR and stem cell factor (SCF). The human
      megakaryoblastic leukemia cell lines UT-7 and M07e, human chronic myelogenous
      leukemia cell line K-562, and erythroleukemia cell line TF-1 were used to assess
      CAR-SCF-assisted Ad5-mediated gene transfer. Hematopoietic cell lines were
      infected with an Ad5 vector (Ad5-eGFP) or a fiber-mutant Ad5/F35 (Ad5/F35-eGFP)
      expressing the enhanced green fluorescent protein gene in the presence or absence
      of CAR-SCF. RESULTS: Twenty-four hours after infection, more than 80% of M07e
      cells infected in the presence of CAR-SCF were eGFP-positive, compared with very
      few eGFP-positive cells following Ad5-eGFP infection in the absence of CAR-SCF.
      The enhancement of Ad5-eGFP infection by CAR-SCF was greater than that caused by
      Ad5/F35-eGFP (50%). The ability of CAR-SCF to enhance Ad5-eGFP infectivity was
      highly dependent on cellular c-Kit expression levels. Furthermore, CAR-SCF also
      enhanced Ad5-mediated gene transfer into human primary CD34(+) cells.
      CONCLUSIONS: The CAR-SCF fusion protein assists Ad5-mediated transduction to c
      Kit(+) CAR(-) hematopoietic cells. The use of this fusion protein would enhance a
      utility of Ad5-mediated hematopoietic cell transduction strategies.

PMID- 14601131
TI  - Long-term transgene expression in cardiac and skeletal muscle following fetal
      administration of adenoviral or adeno-associated viral vectors in mice.
AB  - BACKGROUND: In utero gene transfer may provide advantages for the correction of
      congenital genetic disorders. In the present study we compare the ability of
      adenovirus (AdCMVLacZ), and two serotypes of adeno-associated virus (AAVCMVLacZ
      serotypes 2 and 2/5), to target cardiac and skeletal muscle after prenatal
      systemic or intramuscular injection in mice and assess the immune response to the
      vectors. METHODS: Day 14 gestation fetal mice underwent direct intraperitoneal or
      intramuscular injection of AdCMVLacZ, and AAVCMVLacZ serotypes 2 and 2/5 vectors.
      Tissues were processed for beta-galactosidase expression in frozen or high
      resolution thin plastic sections at early and late time points. Neutralizing
      antibodies to Ad and AAV were analyzed in separate fetal experimental and
      neonatal or adult control groups after administration and re-administration of
      the vectors. RESULTS: A single injection of each vector in utero resulted in
      sustained expression of beta-galactosidase transgene in skeletal and cardiac
      muscle. Transgene expression was detected for the length of the study, i.e. 86,
      58, and 31 weeks after birth for AdCMVLacZ, and AAVCMVLacZ serotypes 2 and 2/5,
      respectively. High-level expression in the myocardium was observed independent of
      the vector or route of administration. Neutralizing antibody responses to AAV and
      Ad antigens were reduced and long-term expression in muscle was not ablated on
      postnatal re-administration of vector. CONCLUSIONS: Sustained, high-level cardiac
      and skeletal muscle transgene expression can be obtained after prenatal gene
      transfer with each of these vectors. The potential for immune response to viral
      antigens is altered, but not entirely ablated after in utero exposure.

PMID- 14601132
TI  - Antisense oligodeoxynucleotide against HST-1/FGF-4 suppresses tumorigenicity of
      an orthotopic model for human germ cell tumor in nude mice.
AB  - BACKGROUND: Overexpression of the fibroblast growth factor HST-1/FGF-4 gene is
      thought to mediate growth properties and malignancy in human testicular germ cell
      tumors. We have studied the effect that an antisense oligodeoxynucleotide against
      HST-1/FGF-4 suppresses tumorigenicity of a human germ cell tumor. METHODS AND
      RESULTS: To test whether HST-1/FGF-4 could be the target of gene therapy for
      testicular carcinoma, 20-mer phosphorothioate oligodeoxynucleotides (ODNs)
      directed against human HST-1/FGF-4 were analyzed for their antitumor activity.
      The antisense HST-1/FGF-4 ODNs suppressed HST-1/FGF-4 production by NEC8 human
      nonseminomatous germ cells and inhibited their cell growth in vitro. Furthermore,
      after orthotopic implantation of NEC8 cells, combined treatment with antisense
      HST-1/FGF-4 ODNs and Atelocollagen significantly inhibited the growth of
      testicular tumors as well as the incidence of lymph node metastasis. In contrast,
      administration of antisense ODNs alone was less effective. CONCLUSIONS:
      Collectively, these results indicate that the antisense method against HST-1/FGF
      4 gene expression will be a novel therapeutic approach for male germ cell tumors.
      The use of Atelocollagen-mediated administration of the antisense HST-1/FGF-4
      ODNs may be useful in enhancing the effects of antisense therapy.

PMID- 14601133
TI  - Advantages and limitations of particle-mediated transfection (gene gun) in cancer
      immuno-gene therapy using IL-10, IL-12 or B7-1 in murine tumor models.
AB  - BACKGROUND: Previous studies have shown that particle-mediated transfection (PMT;
      gene gun) is an efficient method of non-viral gene transfer. We have examined the
      advantages and limitations of PMT in cancer immuno-gene therapy using IL-10, IL
      12 or B7-1, all of which have been shown to be effective in murine tumor models
      using retroviral vectors. METHODS: Murine cell lines (MCA205, MCA207, NIH-3T3)
      were treated with in vitro PMT, liposome-mediated transfection (LMT) or
      retroviral transfection. In vivo PMT was also examined for in vivo experiments
      using C57BL/6. RESULTS: Transfection efficiency and cytokine expression of PMT
      were similar to those of LMT, another non-viral approach, in culture when murine
      adherent cells were used. Tumor establishment of MCA205 was suppressed when they
      were transfected with the mIL-12 and/or mB7-1 gene using PMT in vitro. In a
      treatment of established tumor, vaccination with tumor cells transfected with an
      IL-12 gene suppressed tumor growth, whereas a B7-1 gene was not effective. When
      an IL-10 gene was used to supply a high level of expression for antitumor
      effects, neither in vitro nor in vivo PMT could suppress even tumor
      establishment. These failures appear to be caused by the characteristics of PMT
      which allows high, but transient, expression of transfected genes. CONCLUSIONS:
      Particle-mediated transfection is a useful non-viral transfection method in a
      system which does not require high-level gene expression for a prolonged time of
      period.

PMID- 14601134
TI  - Mice body weight gain is prevented after naked human leptin cDNA transfer into
      skeletal muscle by electroporation.
AB  - BACKGROUND: In this investigation, the feasibility of gene therapy for obesity by
      electroporational transfer of naked plasmid with leptin cDNA into skeletal muscle
      was tested. Both young and adult mice were studied. METHODS: Human leptin cDNA
      was attached to the human insulin precursor secretion signal peptide gene. The
      fused gene was then inserted into the mammalian expression vector pcDNA3.1(-) and
      transferred into skeletal muscle of normal female mice using electroporation.
      RESULTS: During the time of exogenic gene expression, daily food intake of leptin
      cDNA-treated mice was observed to be lower than the control. The body weight gain
      was prevented efficaciously regardless of if they were young or adult. At the 7th
      week after gene transfer, the body weight of both young and adult leptin cDNA
      treated mice was about 20% lighter than the control. Although the body weight of
      pair fed controlled adult mice was close to the leptin cDNA-treated mice at the
      8th week, they were always heavier than the leptin cDNA-treated mice before this
      time. The levels of retroperitoneal fats and serum TG of leptin cDNA-treated mice
      were markedly lower than that of the control. The relative serum hyperleptinemic
      level could last for about 2 months. The expression of leptin cDNA in muscle
      cells was also detected by RT-PCR. The levels of serum insulin and glucose of
      leptin cDNA-treated mice decreased slightly. Our data also showed that the
      hyperleptinmia resulted in uterus expansion in young mice, but not in the adults.
      CONCLUSION: The present study provides evidence of successful electroporation of
      naked plasmid DNA transfer for prevention or treatment of mice obesity.

PMID- 14601135
TI  - Long-term control of food intake and body weight by hydrodynamics-based delivery
      of plasmid DNA encoding leptin or CNTF.
AB  - BACKGROUND: Obesity contributes to many common diseases, including cardiovascular
      and metabolic disorders such as diabetes, hypertension, and stroke. Leptin and
      ciliary neurotrophic factor (CNTF), two members of the cytokine family, play
      important roles in controlling food intake and body weight in rodents. Here, we
      used the hydrodynamics-based gene delivery technique to introduce leptin and CNTF
      expression plasmids, pCAGGS-leptin and pCAGGS-CNTF, into mice and to assess
      whether they could induce high expression of leptin or CNTF and reduce food
      intake and body weight in the mice. METHODS: Plasmid DNA (50 microg) in lactated
      Ringer's solution (0.1 ml/g body weight) was rapidly injected into the tail vein
      of 4-week-old male MCH-ICR mice. RESULTS: After a single injection, serum leptin
      peaked (at 32.0 +/- 3.1 ng/ml) 2 days after the injection, and serum CNTF peaked
      (at 22.0 +/- 0.8 microg/ml) 1 day after the injection. The high expression of
      either leptin or CNTF was sustained and dramatically reduced food intake (CNTF
      and leptin group vs. control group; 2.3 +/- 0.5 and 3.1 +/- 0.5 g/day vs. 4.8 +/-
      0.6 g/day; p < 0.001) and body weight (3 weeks after the injection; CNTF and
      leptin group vs. control group; -19.5% and +3.3% vs. +33.3-47.5%; p < 0.001) in
      the mice, suggesting potent in vivo activities for these exogenously expressed
      proteins. CONCLUSIONS: These results suggest that hydrodynamics-based gene
      delivery could have broad applications in the study of appetite regulation and
      metabolism.

PMID- 14601136
TI  - Expression of phenylalanine hydroxylase (PAH) in erythrogenic bone marrow does
      not correct hyperphenylalaninemia in Pah(enu2) mice.
AB  - BACKGROUND: Treatment of many inherited liver enzyme deficiencies requires the
      removal of toxic intermediate metabolites from the blood of affected individuals.
      We propose that circulating toxins can be adequately cleared and disease
      phenotype influenced by enzyme expressed in tissues other than the liver, such as
      bone marrow. Our specific hypothesis was that phenylalanine hydroxylase (PAH)
      expressed in bone marrow would lower blood phenylalanine levels in
      hyperphenylalaninemic Pah(enu2) mice, a model of human phenylketonuria (PKU).
      METHODS: Germline-modified marrow PAH-expressing mice were developed using a
      transgene that contained the mouse liver PAH cDNA under the transcriptional
      control of a human beta-globin promoter. Marrow PAH-expressing mice were bred to
      Pah(enu2) mice to generate progeny that lacked liver PAH activity but expressed
      PAH in bone marrow. RESULTS: Marrow PAH expression did not affect the health,
      function, or reproductive capacity of transgenic animals. Hyperphenylalaninemia
      persisted in transgenic Pah(enu2) homozygous mice despite PAH activity in marrow
      lysates, and was not altered following supplementation with tetrahydrobiopterin
      (BH(4)), a required cofactor for PAH. PAH activity measured in intact marrow
      cells was significantly lower than in marrow lysates; no such difference was
      measured in isolated hepatocytes vs. liver homogenate. CONCLUSIONS: Marrow PAH
      expression did not correct hyperphenylalaninemia in Pah(enu2) mice. Phenylalanine
      clearance may have been limited by the natural perfusion rate of the marrow
      compartment, by insufficient PAH expression in marrow, or by other cellular
      factors affecting phenylalanine metabolism in intact marrow cells. Differences in
      PAH activity measured in intact marrow cells vs. cell lysates suggest that
      hepatocytes and PAH-expressing marrow cells are fundamentally different in their
      ability to metabolize phenylalanine. The efficacy of bone-marrow-directed gene
      therapy as a metabolic sink in the treatment of phenylketonuria may be limited,
      although further experiments with greater marrow PAH expression levels will be
      necessary to definitively prove this conclusion.

PMID- 14601137
TI  - Pre-administration of angiopoietin-1 followed by VEGF induces functional and
      mature vascular formation in a rabbit ischemic model.
AB  - BACKGROUND: Angiopoietin-1 (Ang1) and vascular endothelial growth factor (VEGF)
      play important roles in vascular formation and maturation, suggesting that the
      combination of these two would be a promising therapy for ischemia. However, it
      remains unclear what the best schedule of administration of these cytokines might
      be. METHODS: Six experimental groups were used to prepare the rabbit ischemic
      hindlimb model following naked plasmid intramuscular administration as follows:
      empty vector (C), single gene (Ang1, A; VEGF, V), Ang-1 followed by VEGF (A - V),
      co-administration of Ang1 and VEGF (A + V), and VEGF followed by Ang1 (V - A).
      RESULTS: Thirty days after gene administration, A - V showed a significantly
      increased blood pressure and blood-flow recovery in the ischemic limb compared
      with the control group. Histological findings by alpha-smooth muscle-actin (alpha
      SMA) staining revealed that the two combination groups had more mature vessels as
      compared with the control group. Significantly, A - V revealed the highest
      density of alpha-SMA-positive vessels compared with VEGF alone or Ang1 alone.
      Angiographic assessment revealed that A - V had a greater increased arterial
      diameter compared with VEGF alone. Edema, one of the major adverse effects
      induced by VEGF, was not found in A - V throughout the experiments, while VEGF
      alone and V - A showed severe edema induced by VEGF. CONCLUSIONS: The pre
      administration of Ang1 followed by VEGF resulted in an improvement of hemodynamic
      status, an increased number of vessels covered with alpha-actin-positive mural
      cells, and prevention of VEGF-mediated edema. Thus, priming by Ang1 gene
      administration would be beneficial for therapeutic angiogenesis in VEGF gene
      therapy.

PMID- 14601139
TI  - Acoustic noise concerns in functional magnetic resonance imaging.
AB  - Magnetic resonance (MR) acoustic scanner noise may negatively affect the
      performance of functional magnetic resonance imaging (fMRI), a problem that
      worsens at the higher field strengths proposed to enhance fMRI. We present an
      overview of the current knowledge on the effects of confounding acoustic MR noise
      in fMRI experiments. The principles and effectiveness of various methods to
      reduce acoustic noise in fMRI are discussed, practical considerations are
      addressed and recommendations are made.

PMID- 14601140
TI  - Accuracy and applications of group MEG studies using cortical source locations
      estimated from participants' scalp surfaces.
AB  - We contend that powerful group studies can be conducted using
      magnetoencephalography (MEG), which can provide useful insights into the
      approximate distribution of the neural activity detected with MEG without
      requiring magnetic resonance imaging (MRI) for each participant. Instead, a
      participant's MRI is approximated with one chosen as a best match on the basis of
      the scalp surface from a database of available MRIs. Because large inter
      individual variability in sulcal and gyral patterns is an inherent source of
      blurring in studies using grouped functional activity, the additional error
      introduced by this approximation procedure has little effect on the group
      results, and offers a sufficiently close approximation to that of the
      participants to yield a good indication of the true distribution of the grouped
      neural activity. T1-weighted MRIs of 28 adults were acquired in a variety of MR
      systems. An artificial functional image was prepared for each person in which
      eight 5 x 5 x 5 mm regions of brain activation were simulated. Spatial
      normalisation was applied to each image using transformations calculated using
      SPM99 with (1) the participant's actual MRI, and (2) the best matched MRI
      substituted from those of the other 27 participants. The distribution of
      distances between the locations of points using real and substituted MRIs had a
      modal value of 6 mm with 90% of cases falling below 12.5 mm. The effects of this
      approach on real grouped SAM source imaging of MEG data in a verbal fluency task
      are also shown. The distribution of MEG activity in the estimated average
      response is very similar to that produced when using the real MRIs.

PMID- 14601141
TI  - Transient human cortical responses during the observation of simple finger
      movements: a high-resolution EEG study.
AB  - High-resolution event-related potentials (ERPs) were used to model the
      hemispherical representation of the transient cortical responses relating to the
      observation of movement during execution (right or left aimless finger
      extension). Subjects were seated in front of the observed person and looked at
      both their own and the observer's hand to receive similar visual feedback during
      the two conditions. In a visual control condition, a diode light moved at the
      observed person's hand. A first potential accompanying the movement execution
      peaked at about +110 msec over the contralateral somatomotor areas. It was
      followed by a potential (P300) peaking at about +350 msec over the central
      midline. In contrast, the potentials accompanying the movement observation peaked
      later over parietal-occipital other than somatomotor areas (N200 peak, +200 msec;
      P300 peak, +400 msec). Notably, the N200 was maximum in left parietal area
      whereas the P300 was maximum in right parietal area regardless the side of the
      movement. They markedly differed by the potentials following the displacement of
      the diode light. These results suggest a rapid time evolution (approximately 200
      400 msec) of the cortical responses characterizing the observation of aimless
      movements (as opposite to grasping or handling). The execution of these movements
      would mainly involve somatomotor cortical responses and would be scarcely founded
      on the visual feedback. In contrast, the observation of the same movements
      carried out by others would require dynamical responses of somatomotor and
      parietal-occipital areas (especially of the right hemisphere), possibly for a
      stringent visuospatial analysis of the motor event.

PMID- 14601142
TI  - Physiological evidence of interaction of first- and second-order motion processes
      in the human visual system: a magnetoencephalographic study.
AB  - Humans have several mechanisms for the visual perception of motion, including one
      that is luminance-based (first-order) and another that is luminance-independent
      (second-order). Recent psychophysical studies have suggested that significant
      interaction occurs between these two neural processes. We investigated whether
      such interactions are represented as neural activity measured by
      magnetoencephalography (MEG). The second-order motion of a drifting sinusoidal
      grating, which is defined by the speed of the dot motion, did not generate a
      response. Apparent motion (AM) of the square area, defined by the speed of
      randomly moving dots, evoked a magnetic response whose latency and amplitude
      changed with the distance that the area moved (a second-order characteristic),
      though the response properties were significantly different from those for the
      first-order AM. AM, defined by both first- and second-order attributes, evoked an
      MEG response and the latencies and the amplitudes were distributed between those
      for the first- and second-order motions. The cortical source of the response was
      estimated to be around MT+. The results show a distinct difference in the neural
      processing of the second-order motion that cannot be explained by the difference
      in visibility, and they indicate that the interaction of the neural processes
      underlying first- and second-order motion detection occurs before the MEG
      response. Our study provides the first physiological evidence of a neural
      interaction between the two types of early motion detection.

PMID- 14601144
TI  - Immunoelectron microscopic studies on protein gene product 9.5 and calcitonin
      gene-related peptide in vallate taste cells and related nerves in the guinea pig.
AB  - On the basis of our previous report that protein gene product 9.5 (PGP 9.5)
      immunoreactive nerve fibers and taste cells and calcitonin gene-related peptide
      (CGRP)-immunoreactive nerve fibers are found in guinea pig vallate papillae
      [Huang and Lu (1996b) Arch. Histol. Cytol. 59:433-441]. We speculated that PGP
      9.5 might be a marker for taste receptor cells and that CGRP might play an
      important role in taste transmission. We, therefore, performed an
      immunohistochemical and ultrastructural analysis of taste cells and related
      nerves in guinea pig vallate papillae. In the connective tissue of the vallate
      papilla, the ultrastructural data revealed that the PGP 9.5-immunoreactive nerve
      fibers were both myelinated and unmyelinated. The CGRP-immunoreactive nerve
      fibers were unmyelinated and surrounded by the cytoplasm of Schwann cells as were
      the non-immunoreactive fibers. In the vallate taste buds, only type III cells,
      which make synaptic contacts with intragemmal nerves, were PGP 9.5
      immunoreactive, while the nerve terminals making synaptic contact with the
      underlying type III cells were CGRP-immunoreactive. From these observations, we
      conclude that: (1) PGP 9.5 might be a useful specific marker for type III cells
      in guinea pig vallate taste buds; and (2) CGRP-containing nerve fibers might be
      primarily involved in the neural transmission of taste stimuli.

PMID- 14601143
TI  - Detection and quantification of a wide range of fMRI temporal responses using a
      physiologically-motivated basis set.
AB  - The temporal dynamics of fMRI responses can span a broad range, indicating a rich
      underlying physiology, but also posing a significant challenge for detection. For
      instance, in human auditory cortex, prolonged sound stimuli ( approximately 30
      sec) can evoke responses ranging from sustained to highly phasic (i.e.,
      characterized by prominent peaks just after sound onset and offset). In the
      present study, we developed a method capable of detecting a wide variety of
      responses, while simultaneously extracting information about individual response
      components, which may have different neurophysiological underpinnings.
      Specifically, we implemented the general linear model using a novel set of basis
      functions chosen to reflect temporal features of cortical fMRI responses. This
      physiologically-motivated basis set (the "OSORU" basis set) was tested against
      (1) the commonly employed "sustained-only" basis "set" (i.e., a single smoothed
      "boxcar" function), and (2) a sinusoidal basis set, which is capable of detecting
      a broad range of responses, but lacks a direct relationship to individual
      response components. On data that included many different temporal responses, the
      OSORU basis set performed far better overall than the sustained-only set, and as
      well or better than the sinusoidal basis set. The OSORU basis set also proved
      effective in exploring brain physiology. As an example, we demonstrate that the
      OSORU basis functions can be used to spatially map the relative amount of
      transient vs. sustained activity within auditory cortex. The OSORU basis set
      provides a powerful means for response detection and quantification that should
      be broadly applicable to any brain system and to both human and non-human
      species.

PMID- 14601145
TI  - A new technique for multiparameter imaging microscopy: use of long decay time
      photoluminescent labels enables multiple color immunocytochemistry with low
      channel-to-channel crosstalk.
AB  - In this report, we describe luminescence imaging microscopy using five different
      photoluminescent dyes in a single specimen. We combined the long decay time
      luminophores, europium(III) chelate, terbium(III) chelate, palladium(II)
      coproporphyrin, and platinum(II) coproporphyrin, with a green nuclear stain, Syto
      25 trade mark, that emits conventional fast decaying fluorescence. The
      luminescence emissions from the five different luminophores were separated from
      each other by the differences in spectra and decay times using time-resolved
      detection. Applicability of this dye-combination for multiparameter analysis of a
      biological object was verified in a mixed population of peripheral blood
      leukocytes. Leukocyte cytocentrifugates were incubated in one step with a
      cocktail of luminophore-conjugated antibodies recognizing neutrophil- and
      lymphocyte-specific markers, followed by rapid staining with a mixture of nuclear
      stain and Pt-porphyrin as an eosinophil stain. The results show that multiple
      luminescent dyes with long decay time can be used together, and in combination
      with a conventional fluorophore. The separation of the signals of the long decay
      time labels was distinctive and enabled reliable identification of different
      leukocyte types, as well as an automated cell count. The long decay time
      luminophores together with time-resolved luminescence imaging microscopy (TR-LIM)
      provide a unique tool for studies of simultaneous expression of multiple antigens
      at the level of a single cell. In comparison with other multiparameter imaging
      techniques, the described technique offers increased accuracy of results,
      simplification of preparation procedure, and dramatic shortening of the total
      processing time. To our knowledge, this is the first time that simultaneous
      fivefold labeling/staining and analysis in a single specimen has been performed
      in the field of immunocytochemistry.

PMID- 14601146
TI  - Localisation of WE-14 immunoreactivity in the developing mouse limbo-corneal
      nerve net.
AB  - WE-14 is generated in subpopulations of chromogranin A immunopositive endocrine
      cells and neurons including those innervating the anterior uvea. This study
      investigated WE-14 in intact sclero-limbo-corneal tissue from embryonic (E17),
      neonatal (N0-N16), and adult mice using immunocytochemistry and confocal scanning
      laser microscopy. Weak WE-14 immunostaining was observed at birth in nerve fibre
      tracts entering the corneal mid-stroma from the limbo-scleral junction.
      Immunopositive fibre tracts were evident throughout the cornea at N3; by N5 the
      mid-stromal plexus had begun to generate fibre populations extending toward the
      developing corneal epithelium, and some varicose fibres terminated amongst the
      developing epithelium. Immunostaining was evident at N7 in the developing limbo
      scleral nerve net and some fibres exhibited a close association with unidentified
      vascular elements. By N11 and in subsequent neonates, the cornea had developed a
      distinct stratified nerve net composed of thick mid-stromal and thinner upper
      stromal nerve fibre bundles; both possessed populations of varicose WE-14
      immunopositive fibres. In the adult, a sub-epithelial network of varicose WE-14
      immunopositive fibres were evident at the limbo-scleral junction. Some fibres
      exhibited a close association with unidentified vascular elements, while others
      extended into the upper peripheral corneal stroma. WE-14 was evident in leashes
      throughout the basal corneal epithelium and generated fibres ramifying between
      the stratified epithelium with some fibres terminating amongst the outermost
      corneal epithelia. This study has demonstrated that WE-14 was evident in the
      limbo-corneal nerve net at birth and that its detection parallels corneal
      development to adulthood, where WE-14 is evident in a subpopulation of nerve
      fibres.

PMID- 14601147
TI  - Three-dimensional computer reconstruction of large tissue volumes based on
      composing series of high-resolution confocal images by GlueMRC and LinkMRC
      software.
AB  - Computer-based visualization of large tissue volumes with high resolution based
      on composing series of high-resolution confocal images is presented. GlueMRC and
      LinkMRC programs are introduced, implementing composition of overlapping series
      of optical sections captured by a confocal microscope, registration and
      subsequent composition of successive confocal stacks. Both programs are using an
      interactive approach in combination with automatic algorithms for image
      registration. Further, the method for obtaining surface renderings of
      microscopical structure under study is described. For this purpose, structure
      contours visible in the sections are interactively digitized using a Colon plug
      in module running in Ellipse environment. Then the coordinates of the contours
      are processed by special modules in the graphic programming environment IRIS
      Explorer and the structure surface is rendered. The method is shown on the 3-D
      reconstruction of the capillary bed of human placental villi and chick embryonic
      gut and its vascular bed.

PMID- 14601148
TI  - Transmission electron microscopic observations of membrane effects of antibiotic
      cecropin B on Escherichia coli.
AB  - The pathway of cell membrane lysis by the peptide antibiotic cecropin B (CB),
      which contains both a hydrophobic and an amphipathic alpha-helix, was analysed by
      assessing the morphological changes of Escherichia coli following treatment with
      the peptide. Exposure of green fluorescent protein (GFP)-expressing E. coli to CB
      does not lead to an efflux of GFP. Moreover, transmission electron microscopic
      (TEM) examination of cecropin B-treated cells showed that severe swelling
      precedes cell death and that the outer membrane becomes distended away from the
      plasma membrane. Using immuno-gold staining and TEM of E. coli expressing the
      maltose-binding protein in the cytoplasm, it was apparent that the protein
      remains restricted to the cytoplasmic compartment. These observations suggest
      that CB causes gross disruption of the outer membrane of Gram-negative bacteria.
      Circular dichroism measurements of CB in the presence of cell membrane-mimicking
      liposomes showed that CB forms secondary structure dependent on the ratio of
      [lipid]/[peptide]. These observations from this study are important for the
      future design of custom antimicrobial peptides.

PMID- 14601149
TI  - Effects of aging on neurons and glial cells from the superficial layers of the
      superior colliculus in rats.
AB  - The aim of this study was to investigate the effect of aging on glial cells and
      neurons from the superficial layers of the superior colliculus in rats. We used
      stereological methods to estimate the volume of the superficial layers, neuron
      size, and the number of neurons and glial cells in Wistar male rats aged 3, 24,
      26, and 28 months. A 32.6% volume increase was found in the stratum griseum
      superficiale between the ages of 3 and 26 months, while in the 28-month-old
      animals a 19% decrease was observed. The stratum opticum did not show any changes
      in volume with age. Also, our analysis revealed a process of somatic and nuclear
      atrophy in the neurons of the superficial layers in animals aged 26 and 28
      months. On the other hand, no statistically significant differences were found in
      the numbers of neurons. The number of glial cells in the stratum griseum
      superficiale showed an increase between the 3rd and 26th month, while the stratum
      opticum suffered no change.

PMID- 14601150
TI  - Induced maturation of frog mast cells by nerve growth factor during ontogenesis.
AB  - The effect of nerve growth factor (NGF) on ontogenesis of frog mast cells was
      investigated in vivo by histochemical, morphometric, and ultrastructural
      analysis. Three groups of tadpoles at various stages of development were used. In
      the first group, the larvae received i.p. injections of 1 ng NGF/g; the second
      group received 10 ng NGF/g, while the control group received only the vehicle.
      The first recognizable mast cells arose symmetrically in the tongue at stage 26
      of Witschi's standard table. At stages 26 and 29, the mast cell number in the NGF
      injected tadpoles was significantly higher than the control group. From stage 29
      onward, the mast cell number rapidly increased in all groups. No significant
      differences in mast cell number were observed between the control group and the
      NGF-injected groups at stages 31 and 33. Electron microscopy revealed that at
      metamorphic climax (stage 33), the mast cells in the NGF-treated groups were more
      mature than those in the control group. Therefore, nerve growth factor at early
      stages of tadpole development is likely to induce differentiation of mast cell
      precursors, while at later stages it is likely to induce maturation of immature
      mast cells. The close anatomical association between mast cells and perineurium,
      observed during nerve development, is intriguing. Already in the early stages of
      nerve development, the mast cells form a network around Schwann cell-axon
      complexes, together with the perineurial cells. At climax, the mast cells are
      located between the perineurial layers, suggesting that they may play a role in
      the tissue-nerve barrier of the perineurium. Nerve growth factor also seems to
      induce perineurial cell maturation.

PMID- 14601151
TI  - Temporal and topographic ultrastructural alterations of rat heart myofibrils
      caused by thyroid hormone.
AB  - In order to further our understanding regarding the temporal and topographic
      ultrastructural aspects of the myocardium under thyrotoxicosis, thyroxine (T4; 25
      and 100 microg/100 g bw) was administered to young rats 24 hours after birth
      until 15 days. The animals were then sacrificed, the hearts excised and weighed,
      and the ventricle tissue samples were then processed for confocal and
      transmission electron microscopy. At 48/72 hours and 1 week after initiation of
      T4 treatment with 100 microg/100 g bw, numerous lamellar bodies (probably formed
      by phospholipids) progressively accumulated in the heart. These bodies were
      observed in the cytosol, inside mitochondria and in the extracellular matrix. At
      2 weeks of T4 treatment with 100 microg/100 g bw, lamellar bodies were virtually
      absent. Changes in cell shape, disorganization of intercellular junctions, and
      substantial myofibrillar disarray were observed in many cardiomyocytes. A
      gradient of myofibrillar disarray, which increased in abundance and intensity
      from the endocardium to the epicardium, was also observed. Immunocytochemical
      staining for desmin showed that the arrangement of this protein was disorganized
      in many cells of T4-treated rats as compared with normal ones, confirming
      ultrastructural data. The predominant appearance of myofibrillar disarray,
      associated with disorganization of cytoskeletal proteins in the deep myocardium,
      may be due to higher mechanical wall stress and consequent higher metabolic
      demand. Alternatively, differential sensitivity of cardiomyocytes to thyroid
      hormone in different areas is also a possibility.

PMID- 14601152
TI  - Willingness to pay methods in health care: a sceptical view.

PMID- 14601153
TI  - How much confidence should we place in efficiency estimates?
AB  - Ordinary least squares (OLS) and stochastic frontier (SF) analyses are commonly
      used to estimate industry-level and firm-specific efficiency. Using cross
      sectional data for English public hospitals, a total cost function based on a
      specification developed by the English Department of Health is estimated.
      Confidence intervals are calculated around the OLS residuals and around the
      inefficiency component of the SF residuals. Sensitivity analysis is conducted to
      assess whether conclusions about relative performance are robust to choices of
      error distribution, functional form and model specification. It is concluded that
      estimates of relative hospital efficiency are sensitive to estimation decisions
      and that little confidence can be placed in the point estimates for individual
      hospitals. The use of these techniques to set annual performance targets should
      be avoided.

PMID- 14601154
TI  - If the price is right: vagueness and values clarification in contingent
      valuation.
AB  - The use of willingness to pay to value the benefits of health care is increasing.
      Much of this work assumes that health preferences are well formed or 'complete'
      and readily revealed if the right question is asked in the right way. We examined
      this assumption, seeking evidence in a mixed-methods study that explored the
      meaning and implications of vague responses to a payment-scale based willingness
      to pay exercise.One-half of the sample said that their vagueness meant that their
      maximum willingness to pay was actually greater than the amount that they had
      previously said it was. Thirty percent agreed that they would probably pay pound
      10 more than a sum that they had previously said they would most definitely not
      pay, if they found this to be the cost of the vaccine. Interview data supported
      the view that the payment scale had failed to elicit the maximum willingness to
      pay and that some participants used the information on cost to help clarify their
      values, in contrast to the theory underpinning willingness to pay. The results
      suggest a need to consider values-clarification in health economic evaluations.

PMID- 14601155
TI  - Catastrophe and impoverishment in paying for health care: with applications to
      Vietnam 1993-1998.
AB  - This paper presents and compares two threshold approaches to measuring the
      fairness of health care payments, one requiring that payments do not exceed a pre
      specified proportion of pre-payment income, the other that they do not drive
      households into poverty. We develop indices for 'catastrophe' that capture the
      intensity of catastrophe as well as its incidence and also allow the analyst to
      capture the degree to which catastrophic payments occur disproportionately among
      poor households. Measures of poverty impact capturing both intensity and
      incidence are also developed. The arguments and methods are empirically
      illustrated with data on out-of-pocket payments from Vietnam in 1993 and 1998.
      This is not an uninteresting application given that 80% of health spending in
      that country was paid out-of-pocket in 1998. We find that the incidence and
      intensity of 'catastrophic' payments - both in terms of pre-payment income as
      well as ability to pay - were reduced between 1993 and 1998, and that both
      incidence and intensity of 'catastrophe' became less concentrated among the poor.
      We also find that the incidence and intensity of the poverty impact of out-of
      pocket payments diminished over the period in question. Finally, we find that the
      poverty impact of out-of-pocket payments is primarily due to poor people becoming
      even poorer rather than the non-poor being made poor, and that it was not
      expenses associated with inpatient care that increased poverty but rather non
      hospital expenditures.

PMID- 14601156
TI  - Estimating mean hospital cost as a function of length of stay and patient
      characteristics.
AB  - Statistical models have been used to assess the influence of clinical and
      demographic factors on hospital charge and length of stay (LOS). Hospital costs
      constitute a significant proportion of overall expenditure in health care. With
      escalating costs, knowing the correlates of LOS and in-hospital cost is important
      for decisions on allocating resources. However, hospital charge and LOS are
      correlated. We describe two regression models that permit estimation of mean
      charges as a function of patient hospital stay and adjust for the influence of
      patient characteristics and treatment procedures on LOS and charge. In the first
      model, the mean charge over a specified duration is a weighted average of the
      expected cumulative charge, with weighting determined by the distribution of LOS.
      The second model for LOS and charge explicitly accounts for their correlation and
      yields estimates of the average charge per average LOS. The methods are applied
      to assess mean charges and mean charge per day by cardiac procedure in a cohort
      of patients hospitalized for acute myocardial infarction, while adjusting for the
      impact of patient demographic and clinical factors on LOS and charge. For
      relatively short hospital stays, and when only total hospital charges are
      available, these models provide a flexible approach to estimating summary
      measures on resource use while controlling for the effects of covariates on LOS
      and charge.

PMID- 14601157
TI  - Illustrating the impact of including future costs in economic evaluations: an
      application to end-stage renal disease care.
AB  - There are strong theoretical arguments for including future costs for related and
      unrelated medical care and non-medical expenditures within economic evaluations.
      Nevertheless, there is limited data on how inclusion of such costs affects the
      cost effectiveness of medical interventions in practice. For a low-cost
      intervention that improves survival in end-stage renal disease (ESRD) patients,
      we sought to determine how the inclusion of future costs for related medical care
      (i.e. dialysis and transplantation) and for unrelated medical care and non
      medical expenditure would affect the magnitude of the cost per QALY ratio. We
      performed a cost-utility analysis comparing hemodialysis using a synthetic
      dialyser (the current treatment of choice in Canada) with the historical gold
      standard treatment (use of a cellulose dialyser). We contrasted the results of
      the analysis including and excluding various measures of future costs. While the
      inclusion of future costs for unrelated medical care and non-medical expenditures
      had a significant impact on the cost per QALY ratio, the size of the cost per
      QALY ratio was most sensitive to inclusion of future costs for related medical
      care. Our analysis shows that even relatively inexpensive interventions that
      extend survival of dialysis patients may not be cost-effective since, by
      extending survival, the extra outpatient dialysis costs that are incurred are
      large. Inclusion of such costs (which, in and of itself, is methodologically
      correct) in economic evaluations in this area may mitigate against the acceptance
      of interventions that are relatively inexpensive themselves but which improve
      patient survival.

PMID- 14601158
TI  - Estimating the marginal value of 'better' research output: 'designed' versus
      'routine' data in randomised controlled trials.
AB  - We recently completed a study which demonstrated that the costs of health
      technology assessment (HTA) by randomised controlled trial (RCT) can be reduced
      by substituting routine datasets for data designed and collected specifically for
      a trial. This cost reduction, however, had the effect of reducing the quality of
      the research output. In the present study we attempted to tease out the values
      attached to the 'better' information provided by designed data RCTs using a mock
      grants committee. Two valuation techniques, implied values and willingness to
      pay, were used. Ex ante valuations were determined by comparing alternative
      research proposals - a more costly version using designed data and a cheaper
      version using routine data. Ex post valuations were determined by comparing
      results of both versions. The exercise was performed on four exemplar studies.
      Overall, the committee expressed a general lack of trust towards routine data
      both ex ante and ex post and placed high values on the better information from
      the designed data studies - particularly information on preferences. This
      suggests that currently available routine datasets are not perceived to be able
      to provide efficient alternatives to designed data for RCTs.

PMID- 14601162
TI  - Nickel-catalyzed coupling of carbonyl compounds and alkynes or 1,3-dienes: an
      efficient method for the preparation of allylic, homoallylic, and bishomoallylic
      alcohols.

PMID- 14601159
TI  - A view from the bridge: agreement between the SF-6D utility algorithm and the
      Health Utilities Index.
AB  - BACKGROUND: The SF-6D is a new health state classification and utility scoring
      system based on 6 dimensions ('6D') of the Short Form 36, and permits a
      "bridging" transformation between SF-36 responses and utilities. The Health
      Utilities Index, mark 3 (HUI3) is a valid and reliable multi-attribute health
      utility scale that is widely used. We assessed within-subject agreement between
      SF-6D utilities and those from HUI3. METHODS: Patients at increased risk of
      sudden cardiac death and participating in a randomized trial of implantable
      defibrillator therapy completed both instruments at baseline. Score distributions
      were inspected by scatterplot and histogram and mean score differences compared
      by paired t-test. Pearson correlation was computed between instrument scores and
      also between dimension scores within instruments. Between-instrument agreement
      was by intra-class correlation coefficient (ICC). RESULTS: SF-6D and HUI3 forms
      were available from 246 patients. Mean scores for HUI3 and SF-6D were 0.61 (95%
      CI 0.60-0.63) and 0.58 (95% CI 0.54-0.62) respectively; a difference of 0.03
      (p<0.03). Score intervals for HUI3 and SF-6D were (-0.21 to 1.0) and (0.30-0.95).
      Correlation between the instrument scores was 0.58 (95% CI 0.48-0.68) and
      agreement by ICC was 0.42 (95% CI 0.31-0.52). Correlations between dimensions of
      SF-6D were higher than for HUI3. CONCLUSIONS: Our study casts doubt on the
      whether utilities and QALYs estimated via SF-6D are comparable with those from
      HUI3. Utility differences may be due to differences in underlying concepts of
      health being measured, or different measurement approaches, or both. No gold
      standard exists for utility measurement and the SF-6D is a valuable addition that
      permits SF-36 data to be transformed into utilities to estimate QALYs. The
      challenge is developing a better understanding as to why these classification
      based utility instruments differ so markedly in their distributions and point
      estimates of derived utilities.

PMID- 14601163
TI  - Advances in the synthesis of inorganic nanotubes and fullerene-like
      nanoparticles.
AB  - In analogy to graphite, nanoparticles of inorganic compounds with lamellar two
      dimensional structure, such as MoS(2), are not stable against folding, and can
      adopt nanotubular and fullerene-like structures, nicknamed inorganic fullerenes
      or IF. Various applications for such nanomaterials were proposed. For instance,
      IF-WS(2) nanoparticles were shown to have beneficial effects as solid lubricants
      and as part of tribological surfaces. Further applications of IF for high-tensile
      strength fibers, hydrogen storage, rechargeable batteries, catalysis, and in
      nanotechnology are being contemplated. This Minireview highlights some of the
      latest developments in the synthesis of inorganic nanotubes and fullerene-like
      structures. Some structural aspects and properties of IF, which are distinct from
      the bulk materials, are briefly discussed.

PMID- 14601164
TI  - Synthetic expanded porphyrin chemistry.
AB  - Expanded porphyrins are synthetic analogues of the porphyrins, and differ from
      these and other naturally occurring tetrapyrrolic macrocycles by containing a
      larger central core with a minimum of 17 atoms, while retaining the extended
      conjugation features that are a hallmark of these quintessential biological
      pigments. The result of core expansion is to produce systems with novel spectral
      and electronic features, interesting and, often unprecedented, cation
      coordination properties, and, in many cases, an ability to bind anions in certain
      protonation states. Also adding to the appeal of expanded porphyrins is their
      central role in addressing issues of aromaticity. In many cases, they also
      display structural features, such as decidedly nonplanar "figure-eight" motifs,
      that have no antecedents in the chemistry of porphyrins or related macrocyclic
      compounds. In this Review, the various synthetic approaches now being employed to
      produce expanded porphyrins as well as their various applications-related aspects
      are discussed.

PMID- 14601165
TI  - Chirality transfer from single molecules into self-assembled monolayers.

PMID- 14601166
TI  - Quantitative formation of sandwich-shaped trinuclear silver(I) complexes and
      dynamic nature of their P <=> M flip motion in solution.

PMID- 14601167
TI  - Glycotentacles: synthesis of cyclic glycopeptides, toward a tailored blocker of
      influenza virus hemagglutinin.

PMID- 14601168
TI  - [3+3]Cycloalkyne oligomers: linking groups control intra- and intermolecular
      aggregation by pi-pi interactions.

PMID- 14601169
TI  - Biomimetic control of size in the polyamine-directed formation of silica
      nanospheres.

PMID- 14601170
TI  - Conversion of methane to syngas by a membrane-based oxidation-reforming process.

PMID- 14601171
TI  - InBr3-catalyzed cyclization of glycals with aryl amines.

PMID- 14601172
TI  - Gold is noble but gold hydride anions are stable.

PMID- 14601173
TI  - Dicyanocarbodiimide and trinitreno-s-triazine generated by consecutive photolysis
      of triazido-s-triazine in a low-temperature nitrogen matrix.

PMID- 14601174
TI  - Synthesis of a carbon-linked mimic of the disaccharide component of the tumor
      related SialylTn antigen.

PMID- 14601175
TI  - Unprecedented crystalline super-lattices of monodisperse cobalt nanorods.

PMID- 14601176
TI  - Difluoromethyl phenyl sulfone as a selective difluoromethylene dianion
      equivalent: one-pot stereoselective synthesis of anti-2,2-difluoropropane-1,3
      diols.

PMID- 14601177
TI  - The effect of outer-sphere acidity on chemical reactivity in a synthetic
      heterogeneous base catalyst.

PMID- 14601178
TI  - Oxidative addition of phenylacetylene through C-H bond cleavage to form the MgII
      dpp-bian complex: molecular structure of [Mg[dpp
      bian(H)](C[triplebond]CPh)(thf)2] and its diphenylketone insertion product
      [Mg(dpp-bian)*-[OC(Ph2)C[triplebond]CPh](thf)].

PMID- 14601179
TI  - Dynamics of the simplest reaction of a carbon atom in a tetrahedral environment.

PMID- 14601180
TI  - A combinatorial synthesis of a macrosphelide library utilizing a palladium
      catalyzed carbonylation on a polymer support.

PMID- 14601181
TI  - Competitive binding assays made easy with a native marker and mass spectrometric
      quantification.

PMID- 14601182
TI  - Stable and highly water-dispersible, highly unsaturated carotenoid phospholipids
      surface properties and aggregate size.

PMID- 14601183
TI  - Hydrogenation on metal surfaces: why are nanoparticles more active than single
      crystals?

PMID- 14601184
TI  - Simple access to unsymmetrically substituted, saturated N-heterocyclic carbenes.

PMID- 14601186
TI  - Strike the balance--effect instead of sensationalism.

PMID- 14601187
TI  - Longevity of 2328 chairside Cerec inlays and onlays.
AB  - In a dental practice, 2328 ceramic inlays were placed in 794 patients. The
      restorations were manufactured chairside using Cerec technology and adhesively
      inserted at the same appointment. The clinical performance of the restorations
      was evaluated with the Kaplan-Meier analysis. The probability of survival was
      95.5% after 9 years; 35 Cerec restorations were judged as failures. The prognosis
      for success was not significantly influenced by restoration size, tooth vitality,
      treatment of caries profunda (CP), type of tooth treated, or whether the
      restoration was located in the maxilla or mandible. The most common type of
      failure was the extraction of a tooth. In a clinical follow-up light-microscopic
      examination of 44 randomly selected restorations, an average composite joint
      width of 236.3 microns was found. 45.1% of the restorations exhibited a perfect
      margin, and 47.4% of the investigated joint sections showed underfilled margins.

PMID- 14601188
TI  - Digital photography: exposures, editing images, and presentation.
AB  - The digital camera is one of the most important electronic articles on the wish
      list in the private sector, and professional users are also making increasing use
      of the possibilities that the digital image provides. In dental medicine, nothing
      speaks for the analog image anymore, and thus many dentists are searching for an
      expedient solution. Anyone who is faced with deciding on a digital camera will
      often be confused by the immense variety of models and concepts, which are also
      subject to rapid change. Fortunately for dental medicine, however, the current
      camera generation--both viewfinder and SLR systems--offers quality features which
      will be able to satisfy even high demands for many years.

PMID- 14601189
TI  - Cerec veneers--practical procedure and case presentation.
AB  - The Cerec method offers experienced users the possibility of accomplishing
      veneers chairside which are capable of meeting the highest functional and
      esthetic requirements. "Esthetic shaping" directly on the patient requires a good
      eye for color and form, and this requires training. The present report outlines
      the clinical procedure and presents three clinical cases step by step,
      specifically discussing the external staining technique with Pro-CAD blocks.

PMID- 14601190
TI  - Advanced crown and bridge design.
AB  - The present article describes the CAD construction procedure of copings, reduced
      crowns, anatomical crowns, hybrid bridges, and other construction software
      features contained in the Digident dental CAD/CAM system (Girrbach Dental,
      Pforzheim, Germany). The individual design of a crown or a bridge framework will,
      of course, influence the stability and the longevity of the final dental
      restoration. Especially an anatomically reduced crown framework possesses--in
      comparison to a simple coping design--several advantages, while for some
      materials, a full crown design is esthetically not suitable. An anatomically
      reduced crown design results in a mechanical support of the occlusal cusps, as
      the high strength framework is mechanically more favorable than the veneering
      ceramics or composites. Moreover, the reduced construction of the anatomical
      shape allows the creation of ceramic layers of approximately homogeneous
      thickness. This has the effect that the residual stresses in the veneering
      ceramic after the thermal treatment, i.e., several firing and cooling cycles, are
      minimized. A prerequisite for the computer-aided anatomical construction of
      crowns is the inclusion of adjacent teeth and the articulation of the opposing
      jaw. In these terms, the opposing jaw or a bite impression have to be scanned,
      digitized, and positioned virtually in bite relation. While taking patient
      specific articulator parameters into account, a software-integrated "virtual
      articulator" allows simulation of dynamic occlusion and therefore a computer
      aided reduction of interfering contact points.

PMID- 14601191
TI  - GHA efforts, other collaborative initiatives putting a dent in workforce
      shortage.

PMID- 14601192
TI  - Taking health care quality to the next level.

PMID- 14601193
TI  - Final EMTALA regulations hold no surprises.

PMID- 14601194
TI  - Patient safety during anesthesia: the breathing circuit system.

PMID- 14601195
TI  - The antinociceptive effect of a long-acting nalbuphine preparation in rabbits.
AB  - BACKGROUND: An analgesic with a long-lasting effect is particularly desirable to
      patients suffering from long-standing pain. The aim of this study was to evaluate
      the antinociceptive effect and duration of action of an oily dosage form of
      nalbuphine base and to see whether its effect could last longer compared with
      nalbuphine HCl. METHODS: Male New Zealand White rabbits (n = 6 in each group)
      were used. Two studies were carried out. In study 1, we evaluated the
      antinociceptive effect of intramuscular nalbuphine HCl (in saline) with dosages
      of 25, 50, and 100 mumol/kg. In study 2, we evaluated the antinociceptive effects
      of intramuscular nalbuphine base (in sesame oil) with dosages of 100, 200, and
      400 mumol/kg. In these studies, the vehicles (saline or sesame oil) were used as
      controls. A paw pressure test was used to detect the antinociceptive effect of
      the testing drugs. RESULTS: We found that nalbuphine HCl 25, 50 and 100 mumol/kg
      produced a dose-related antinociceptive effect with durations of action of 1, 1,
      and 1.3 h, respectively. Nalbuphine base 100, 200 and 400 mumol/kg also produced
      a dose-related antinociceptive effect but with longer durations of action of 8,
      24, and 48 h, respectively. On an equimolar basis (100 mumol/kg), nalbuphine base
      produced a 6-fold increase in the duration of action than did nalbuphine HCl.
      CONCLUSIONS: We conclude that intramuscular nalbuphine base produced a relatively
      longer duration of action than did intramuscular nalbuphine HCl.

PMID- 14601196
TI  - The effect of education and clinical practice on knowledge enlightenment to and
      attitudes toward the use of analgesics for cancer pain among physicians and
      medical students.
AB  - BACKGROUND: Insufficient education and limited clinical practice on the part of
      physicians may contribute to the undertreatment of cancer pain in Taiwan. To
      address these concerns, a survey among physicians and fifth-year medical students
      relevant to cancer pain management (CPM) was carried out in a medical school and
      its principal teaching hospital. METHODS: A questionnaire on CPM was sent to 97
      physicians and 78 fifth-year medical students (equivalent to the third-year
      medical students in the United States). The same questionnaire was delivered
      again to these 78 fifth-year medical students after they had completed a modified
      curriculum of anesthesiology with a 4-hour course on introduction to clinical
      pharmacology of CPM. RESULTS: The physicians knowledgeable on pain (physicians of
      anesthesiology, hematology-oncology, or radiation oncology), physicians
      unfamiliar with pain (outside of anesthesiology, hematology-oncology, or
      radiation oncology), and the 5th-yr medical students took similar negative
      attitudes (24-92%, 33-89%, and 23-94%) toward the optimal use of analgesics for
      CPM. As compared, the mean score on knowledge of prescribing opioids of pain
      knowledgeable physicians was 3.60, the highest of all as against 2.61 of other
      physicians and 2.54 of 5th-yr medical students. On attitudes toward prescribing
      opioids, both pain-knowledgeable physicians and other physicians scored a higher
      means, respectively of 3.52 and 2.91 as opposed to 2.68 of 5th-yr medical
      students, the lowest of all. However, seniority or length of clinical practice
      did not improve knowledge or affect attitudes toward CPM. In addition, this 4
      hour course did enable the 5th-yr medical students to take a more positive
      attitude toward and become more knowledgeable on CPM than pain-knowledgeable
      physicians, as a comparison was made. CONCLUSIONS: The effect of accumulation of
      clinical experience and seniority of clinical practice on CPM was limited among
      general physicians, except for clinical specialty on anesthesiology, hematology
      oncology, or radiation oncology. In Taiwan, the knowledge of and positive
      attitude toward CPM could only be conveyed to physicians through undergraduate,
      post graduate or on-job education.

PMID- 14601197
TI  - Nitrous oxide suppresses tonic and phasic nociceptive behaviors but not formalin
      induced c-Fos expression in the rat spinal cord dorsal horn.
AB  - BACKGROUND: The aim of this study was to investigate the anesthetic and analgesic
      effects of subanesthetic concentration of nitrous oxide and to compare these
      effects with halothane and fentanyl. METHODS: The antinociceptive effects were
      assessed in male Sprague-Dawley rats by behavioral responses to phasic and tonic
      nociceptive stimulations and biochemical index of pain, formalin-induced Fos-like
      immunoreactivity (Fos-LI), in spinal cord dorsal horn. Neurological functions
      (proprioception, mental status and motor function) were monitored to determine
      whether or not behavioral responses were impaired by anesthetic action of the
      treatment. Four groups of rats treated with: (1) saline, (2) 75% nitrous oxide
      (0.5 MAC), (3) 0.5% halothane (0.5 MAC) and (4) fentanyl 100 micrograms/kg were
      subject either to graded intensity of CO2 laser stimulation (phasic pain) or s.c.
      injection of 50 microliters 2.5% formalin (tonic pain) in two separate studies.
      All rats in the tonic pain study were killed for immunohistochemistry at 60 min
      after formalin injection. Maximal counts of Fos-LI labelled neurons in rat spinal
      cord dorsal horn were compared according to the laminar distribution. RESULTS: We
      found that all rats exhibited normal righting reflexes regardless of whatever
      treatment. Nitrous oxide and halothane greatly impaired mental status and motor
      function, indicating that both agents could induce a modest degree of sedation
      and paresis at subanesthetic concentrations. Fentanyl increased the threshold
      level to noxious thermal stimulation, and reduced the formalin-induced
      licking/biting behaviors and the number of Fos-LI labelled neurons which are
      predominantly found in the neck of the dorsal horn. Nitrous oxide and halothane
      increased the thermal nociceptive threshold, suppressed licking/biting behavior
      in both early and late phases of the formalin test. Unlike fentanyl, nitrous
      oxide and halothane failed to suppress c-fos expression. The extent and pattern
      of nitrous oxide-induced antinociception was identical to halothane, which is
      known to have little or no analgesic effect. The lack of attenuated biochemical
      response to tonic pain stimulation may suggest that nitrous oxide fails to
      suppress spinal sensitization despite its potent inhibition on behavioral
      hyperalgesia. CONCLUSIONS: These findings suggest that, at the spinal level,
      subanesthetic concentration of nitrous oxide greatly attenuates nociceptive
      behaviors mainly due to a non-selective suppression of behavioral responses that
      are commonly associated with inhalation anesthetic drugs.

PMID- 14601198
TI  - The hypotensive effects of propofol at different sampling sites in
      cardiopulmonary bypass model.
AB  - BACKGROUND: Although propofol has been widely used the uncertainties about its
      pharmacokinetics and pharmacodynamics are still in existence especially on acute
      infusion model. This study was designed to observe the changes of the arterial
      and superior vena cava blood concentrations of propofol during cardiopulmonary
      bypass and to see whichever site is more appropriate for pharmacodynamic studies
      of propofol. METHODS: Eight patients undergoing cardiopulmonary bypass were
      infused rapidly with propofol. Samples were collected concurrently from bypass
      arterial side (Ca) and superior vena cava (Cv) side at 0, 0.5, 1, 1.5, 2, 5, 10,
      20, 30, and 40 minutes after infusion and analyzed with high pressure liquid
      chromatography (HPLC). Arterial blood pressure was also recorded at the same
      time. RESULTS: After administration, the concentration at Ca side was
      significantly higher than that at the corresponding Cv side from 0.5 to 5 min.
      The concentration at Ca side peaked at 0.5 min, then decreased rapidly and
      crossed the Cv curve at approximately 10 min. Thereafter Cv side concentration
      was slightly higher than that of Ca side. The mean arterial blood pressure
      decreased significantly from 1 to 20 min after injection. The change in Cv side
      was significantly consistent with the blood pressure change in the distribution
      phase (r = 0.78, r2 = 0.61 P < 0.001) (0 to 5 min). CONCLUSIONS: There was a
      significant arteriovenous concentration difference of propofol after a rapid
      infusion in the cardiopulmonary bypass model. The hypotensive effect of propofol
      in the distribution phase can be predicted better on Cv side.

PMID- 14601199
TI  - Spinal anesthesia with two different dosages of 0.75% glucose-free ropivacaine: a
      comparison of efficacy and safety in Chinese parturients undergoing cesarean
      section.
AB  - BACKGROUND: We compared the clinical efficacy and safety between 2 doses of 2.5
      ml (18.75 mg) and 3 ml (22.5 mg) of 0.75% glucose free spinal ropivacaine in
      Chinese parturients undergoing Cesarean section. METHODS: In this randomized,
      open-label study, 40 parturients enrolled were divided into two groups: Group A
      received a 2.5 ml 0.75% ropivacaine as opposed to 3 ml in Group B. Sensory and
      motor blocks were assessed during and after surgery until complete recovery.
      Eight standard measurements were taken: time at onset of sensory block; maximum
      cephalic sensory spread; maximum number of blocked segments; time to maximum
      sensory block; duration of sensory block at L3; time at onset of complete motor
      block and duration until complete recovery. Vital signs and any adverse effects
      related to spinal anesthesia were also recorded. RESULTS: Five of the 6 variables
      showed no significant difference between groups A and B: onset time of sensory
      block at L3 was 1.8 +/- 6.7 min vs. 2.3 +/- 9.8 min; maximum cephalic spread was
      T3-4 (C3-T7) vs. T3 (C2-T8); maximum number of blocked segments was 20.7 +/- 3.5
      vs. 20.2 +/- 3.4; time to maximum sensory block 15.4 +/- 5.5 min vs. 20.3 +/-
      15.1 min; time for regression to L3 was 200.8 +/- 59.5 min vs. 215.0 +/- 37.6 min
      and time for complete recovery of motor block 208.5 +/- 55.5 min vs. 226.5 +/-
      461. min. Group B had a significantly faster onset time for complete motor block
      (P < 0.05) 15.4 +/- 5.6 min vs. 10.4 +/- 4.7 min. Moreover, there were no
      significant differences in global hemodynamic changes during and after the
      operation. Transient hypotension attacks were more frequent in group A at the
      beginning of anesthesia, perhaps due to inadequate prehydration. Otherwise, there
      were no differences in adverse effects during or after surgery. CONCLUSIONS: We
      conclude that for Cesarean section in Chinese parturients either 18.75 mg (2.5
      ml) or 22.5 mg (3 ml) 0.75% glucose-free ropivacaine can provide a spinal
      anesthesia of the same efficacy and safety.

PMID- 14601200
TI  - Hypercapnia due to rupture of the unidirectional valve in the inspiratory limb of
      the breathing system after induction of general anesthesia--a case report.
AB  - Malfunction of either inspiratory or expiratory check valve in a breathing
      circuit system may allow carbon dioxide (CO2) rebreathing and result in
      hypercapnia. The subsequent increase of PaCO2 may entail increased sympathetic
      activity which in turn causes serious problems such as tachyarrhythmia and
      myocardial ischemia, particularly in patients who have history of coronary artery
      disease (CAD). Here, we report an incident of rupture of the inspiratory valve in
      the breathing circuit which happened to a patient during induction of general
      anesthesia and eventuated in markedly heightened end-tidal CO2 (EtCO2) of the
      patient. The recognition, related complications and management of the inspiratory
      valve malfunction are discussed.

PMID- 14601201
TI  - Sudden complete obstruction of breathing circuit during postural change upon
      completion of thoracic spinal surgery in a pediatric patient.
AB  - Positioning patients during the perioperative period is a common event to
      anesthesiologists. A variety of complications may arise during this cumbrous
      moment. We describe a rare circumstance that we came across immediately after
      changing the posture of a pediatric patient at the end of thoracic spinal
      surgery. A total occlusion of the combined heat-moisture exchanger (HME) and
      bacterial/viral filter was responsible for breathing circuit obstruction. The use
      of the combined HME and bacterial/viral filter is not entirely riskless during
      general anesthesia.

PMID- 14601202
TI  - Complications of fluid overloading with different distention media in
      hysteroscopy--a report of two cases.
AB  - Complications arising from hysteroscopy are relatively rare events. They occur
      more frequently with operative hysteroscopy than with diagnostic hysteroscopy.
      Hysteroscopic procedures, which are alternatives to hysterectomy for surgical
      treatment of menorrhagia and uterine fibroids, place women to run the risk of
      intravasation of uterine distention fluid. Excessive intravasation can entail
      fluid overload, pulmonary edema, congestive heart failure, and electrolyte
      imbalances. The prerequisite for treatment of hysteroscopic fluid overload is
      knowing the nature of the intravasation fluid and it should be promptly treated
      to prevent neurological sequelae. Almost all serious complications of operative
      hysteroscopy can be avoided if proper precautions are taken and close
      communication is maintained between the gynecologic surgeon, the
      anesthesiologist, and nursing staff. Here, we present two cases of fluid overload
      with acute pulmonary edema and electrolyte imbalance from hysteroscopy with
      different distention media.

PMID- 14601203
TI  - Unusual cause of esophageal perforation during intraoperative transesophageal
      echocardiography monitoring for cardiac surgery--a case report.
AB  - Although esophageal perforation after transesophageal echocardiographic (TEE)
      examination is rare yet the occurrence of this life-threatening complication is
      increasing. We report an unusual esophageal perforation occurring 4 days after
      coronary artery bypass graft surgery and Bentall's procedure. The perforation was
      due to inadvertent injury of the esophagus that was deformed and distorted by a
      large calcified lymph node in the mediastinum during intraoperative TEE
      instrumentation. We suggest that careful preoperative radiological examination of
      the mediastinum should be done to recognize the anatomical pathology in patient
      whose routine chest X-ray has disclosed a large calcified lymph node in the
      mediastinum, if he happens to undergo TEE, so as to avoid disastrous esophageal
      perforation.

PMID- 14601204
TI  - General anesthesia for patients with automatic implantable cardioverter
      defibrillator in place--a case report.
AB  - Automatic implantable cardioverter defibrillator (AICD) was commercially
      available for use in patients with malignant ventricular tachycardia and
      ventricular fibrillation since its meeting with FDA approval in 1985. The number
      of AICD implantation has increased year by year worldwide. It was allowed to be
      used in clinical setting in Taiwan by the Department of Health in April 1997.
      Physicians may come across patients with an implanted AICD undergoing surgery
      unrelated to cardiac issues more frequently. It is also a new challenge to
      anesthesiologists who must make pre-operative evaluation, maintenance during
      operative period and post-operative re-evaluation of the AICD function. We bring
      forward here for discussion a 72-year-old male patient who underwent non-cardiac
      surgery with AICD implantation under general anesthesia. The anesthetic
      precautions of patients with the device are also touched.

PMID- 14601205
TI  - Degrees of preparation.

PMID- 14601206
TI  - Behind the times.

PMID- 14601207
TI  - Put the child first. Interview by Pat Healy.

PMID- 14601208
TI  - Stop it now!

PMID- 14601209
TI  - Hope on the home front. Interview by Sarah Harrison.

PMID- 14601210
TI  - Spirit levels.

PMID- 14601211
TI  - Unjust desserts.

PMID- 14601212
TI  - Nurse practitioner education: what level?
AB  - In the debate about what level of qualification nurse practitioners in the UK
      should possess, the authors argue that honours degree status is sufficient
      preparation for clinical practice. However, they also argue that a master's
      degree should be the standard for nurse practitioners developing highly
      specialised and advanced roles.

PMID- 14601213
TI  - Cystic fibrosis: transition from paediatric to adult care.
AB  - There is a current caseload of 350 children with cystic fibrosis at the Royal
      Brompton Hospital, and adult caseload of more than six hundred. Approximately 100
      young people aged between 13 and 18 will transfer to adult care during the next
      five years. The transfer process between services was identified to be in need of
      review. The initial objectives were to review current practice for young people
      ready to transfer from paediatric to adult care, and to assess the needs of the
      professional, patient and caregivers at this time. In June 2000, a new system was
      introduced to the families, which offered them joint transition consultations
      with paediatric and adult cystic fibrosis care teams. A hospital-wide standard
      for transition was approved. In June 2002 an audit of the transition clinic
      system indicated an improvement in the process of transfer from paediatric to
      adult care. However, further service development is required to cater for the
      challenges and individual needs of adolescents.

PMID- 14601214
TI  - Influenza and pneumococcal disease in the community.
AB  - The authors discuss the aetiology, diagnosis and prevention of influenza and
      pneumococcal disease, identifying who should be vaccinated and those who are at
      risk. Useful information on how to plan an immunisation campaign is also
      outlined.

PMID- 14601215
TI  - The generation gain.

PMID- 14601216
TI  - NMC consultations: is the devil in the detail?

PMID- 14601217
TI  - Building on the success of LEO.

PMID- 14601218
TI  - Doing it by yourself.
AB  - The DoH (1999) describes how it 'needs leaders who are motivated, self aware,
      socially skilled and able to work together with others across professional and
      organisational boundaries'. Self-medication incorporates all professional groups
      and divisions within Calderdale and Huddersfield NHS Trust; we work in
      partnership with the pharmacy departments. The main purpose of any organisation
      in the health and social sector is to ensure that a high quality service is
      delivered to service users (Martin 2001), so self-medication is now being given
      the attention it deserves. Assessment will be integral to every service user's
      stay and will continue throughout their stay, including transfer from secondary
      to primary care. It is expected that following its introduction, quality will
      improve; patients will receive their medication on time and it is anticipated
      that discharge delays will reduce. We acknowledge however that this will be
      difficult to demonstrate, as often medical conditions are cited as reasons for
      admission, not non-compliance with medication regimes. We see ourselves as being
      competent in the roles of change agents and our styles have changed throughout
      the process. We have worked together as equals and focused on one outcome. It
      will call on all our professional and educational skills to mould staff so that
      they are ready to embrace the change. Perhaps the lesson that has been learned so
      far is that, despite meticulous planning, the actions of others for whom we are
      not responsible can seriously disrupt the plan. The opportunity to manage change
      through experiential learning, reflection and the transfer of knowledge has been
      challenging while enhancing our personal growth and self-awareness. The project
      has been extended until March 2004 because of the merger and the associated
      increased workload. Becoming a project manager, leader and change agent has
      proved to be an exciting, interesting and challenging experience, although at
      times we felt isolated. The project has now entered a phase that involves intense
      staff training and phase one of introduction.

PMID- 14601219
TI  - Patient suicide and its effect on staff.
AB  - This framework has proved useful in developing the CARDS team, particularly as
      crisis teams are often at the forefront of many stressful incidents. It is based
      on three important aspects of management: the presence of effective guiding
      policies to equip the team with effective and regularly reviewed procedures,
      supervision at many levels and in its many forms, and fast access to additional
      support, developed by the adult mental health forum, when major incidents occur.

PMID- 14601220
TI  - Managing personality disorders: making positive connections.
AB  - This article has outlined what the author believes to be the essential elements
      of support, guidance and training for staff working with people with personality
      disorders. It can be argued that programmes without these elements compromise not
      only the quality of care but also staff wellbeing. HMP Whitemoor, Cambridgeshire,
      is currently piloting a programme for the assessment and treatment of severe
      personality disorders. The multidisciplinary team is actively working towards the
      principles as defined in this paper, and is also involved in the development of
      skills competencies to underpin the whole process. There are several studies
      underway relating to the needs of the prison's staff team and these will evaluate
      the aforementioned principles and thereby refine the staff support, supervision
      and development structures. There is no apology made for the focus of this
      article being on staff needs. Without them being met, any service designed to
      care and manage people with personality disorders cannot exist, thus returning
      the people this programme is designed to help to a chaotic and crisis-driven
      existence.

PMID- 14601221
TI  - The 'morally active' manager.

PMID- 14601222
TI  - Three centres of excellence for care of lymphoedema patients.

PMID- 14601223
TI  - An investigation into the wound-healing properties of essential oil of Ocimum
      gratissimum linn.
AB  - OBJECTIVE: To investigate the effects of Ocimum oil and two antibacterial
      preparations, Cicatrin (GlaxoWellcome) and Cetavlex (AstraZeneca), on the healing
      of full-thickness excisional and incisional wounds, created under anaesthesia, on
      the back of test and control groups of adult albino rabbits. METHOD: Treatment
      was by topical application of the test substances onto the wound surface for 15
      days. Observation continued for a further six days. Quantitative parameters of
      wound healing were determined daily. Swabs were taken from wound sites that
      appeared not to be healing for identification of wound contaminants and
      sensitivity tests. RESULTS: There was a marked enhancement in the inflammatory
      and proliferative phases of wound healing in the rabbits treated with Ocimum oil,
      suggesting that the oil facilitated the healing process to a greater extent than
      the control and reference products. Wounds treated with Cetavlex showed no sign
      of healing for eight days but responded to Ocimum oil after a three-day wash-out
      period. CONCLUSION: The essential oil Ocimum gratissimum can promote wound
      healing. However, large studies will need to be carried out using domestic pigs,
      followed by clinical trials on human wounds. DECLARATION OF INTEREST: None.

PMID- 14601224
TI  - Pain in pure and mixed aetiology venous leg ulcers: a three-phase point
      prevalence study.
AB  - OBJECTIVE: This study aimed to determine the point prevalence of venous leg ulcer
      pain over three seasons (autumn, winter and spring). It also collated profiles of
      individuals with venous ulceration and described the characteristics of people
      with and without venous leg ulcer pain. METHOD: The study sample comprised 255
      people with pure and mixed venous leg ulcers who were receiving care in a
      Canadian community leg ulcer service. Prevalence was determined by the number of
      individuals who had experienced pain in the past 24 hours. The profile of
      individuals was developed by analysing sociodemographic, circumstance-of-living,
      clinical and health-related quality-of-life data collected on admission to the
      leg ulcer service. RESULTS: Over the three prevalence periods, the prevalence of
      pain for the total sample ranged from 48% to 54%. Prevalences at each of the
      study periods for individuals who had been receiving care for less than 13 weeks,
      and for the first measure of pain only, were almost identical, ranging from 48
      59%. The mean pain-severity score was less than three (out of 10) in all three
      periods. Of the individuals with pain, 50% or more used analgesia and, of these,
      over 75% reported it was effective. The profile of participants with pain was
      similar to those without it, except that the former were significantly more
      likely to have osteoarthritis, a foot ulcer, to have been attending the leg
      service for a shorter time period and to have a lower SF-12 mental health
      component score. CONCLUSION: These results demonstrate that leg ulcer management
      must include pain assessment and consideration of the factors that may be
      associated with pain. A large prospective repeated measures study is needed to
      increase understanding of the extent of pain, the use and efficacy of analgesia,
      and the factors that may be related to experiencing pain.

PMID- 14601225
TI  - Different way of removing dressings could have affected study outcome.

PMID- 14601226
TI  - Can topical negative pressure be used to control complex enterocutaneous
      fistulae?

PMID- 14601227
TI  - The benefits of applying wound-bed preparation into practice.

PMID- 14601228
TI  - Clinical performance of a new silver dressing, Contreet Foam, for chronic exuding
      venous leg ulcers.
AB  - OBJECTIVE: This study aimed to evaluate the safety and performance of a new
      sustained silver-releasing dressing, Contreet Foam (Coloplast A/S), in the
      treatment of moderately to highly exuding chronic venous leg ulcers in which
      healing is delayed due to the presence of bacteria. METHOD: The clinical
      performance of Contreet Foam was studied for four weeks in 25 patients with
      moderately to highly exuding delayed-healing venous leg ulcers. Healing was
      assessed on a weekly basis with reference to the wound-bed tissue composition,
      degree of odour and pain, dressing performance and the dressing's effect on the
      peri-ulcer area. Blood samples were analysed for silver content. RESULTS: Twenty
      three out of 25 patients completed the study. One ulcer healed and no wound
      infections occurred during the study period. A mean 56% reduction in ulcer area
      (from 15.6 to 6.9 cm2) was recorded during the four weeks, and there was a mean
      25% reduction in granulation tissue from dull to healthy after one week. Wound
      odour reduced significantly after one week. Mean dressing wear time was 3.1 days,
      and there were only minimal incidences of leakage. Serum silver levels did not
      exceed reference values. CONCLUSION: Contreet Foam was found to be safe and
      performed well when used in the treatment of delayed-healing chronic venous leg
      ulcers, combining effective antibacterial properties with excellent exudate
      management. DECLARATION OF INTEREST: This study was supported by Coloplast A/S,
      Humlebaek, Denmark.

PMID- 14601229
TI  - Use of a vacuum assisted closure device in pilonidal disease.

PMID- 14601230
TI  - A trial to assess the efficacy and tolerability of Hyalofill-F in non-healing
      venous leg ulcers.
AB  - OBJECTIVE: This single-centre, open, uncontrolled pilot clinical trial set out to
      assess the efficacy and tolerability of Hyalofill-F (a partial benzyl ester
      derivative of hyaluronan), used in combination with compression bandaging, in the
      treatment of venous leg ulcers. METHOD: The 20 patients enrolled into the study
      had venous insufficiency and a leg ulcer that had been refractory to treatment
      for one month. Treatment was continued for eight weeks, with weekly assessments.
      RESULTS: During the study period four of the patients' ulcers healed completely.
      An average wound area reduction of 53.5% was seen in the ulcers that did not
      heal. Differences in ulcer area and ulcer depth between the initial and final
      visit were significant (p < 0.01, p = 0.03). The average healing rate (cm2/week
      reduction) was 1.26 +/- 1.7 (standard deviation). A calculated prognostic index
      was used to identify patients at high risk of a poor response to compression
      therapy (10% probability of wound closure at 120 weeks). These patients
      demonstrated a mean 63% decrease in wound area after eight weeks of treatment
      with Hyalofill-F plus compression bandaging. All wounds showed a positive
      response in terms of granulation-tissue formation. The comfort of the dressing
      was described as excellent. CONCLUSION: The hyaluronan derivative showed
      promising results in initiating the healing process in chronic venous ulcers. It
      was found to be well tolerated and safe to use. However, further clinical trials
      should be performed involving a control group to verify these data. DECLARATION
      OF INTEREST: This study was sponsored by Fidia Advanced Biopolymers, Italy.

PMID- 14601231
TI  - PRIMOS: an optical system that produces three-dimensional measurements of skin
      surfaces.

PMID- 14601232
TI  - [Transportation of critically ill children: guidelines].
AB  - Distribution of the population and the need of centralized care of critically ill
      children make pediatric transport an important issue. This highly complex act is
      often performed by not adequately trained staff. This paper focuses on the
      different phases of pediatric transport: admission to Emergency Department,
      stabilization, transport preparation, transport period, arrival at admitting
      centre. Each centre should develop its own protocol and activate a surveillance
      system.

PMID- 14601233
TI  - [The chronically ill patient in the emergency department: management during
      simultaneous acute diseases].
AB  - The chronically ill patient admitted to an Emergency Department or to a Pediatric
      Emergency Unit for an intercurrent acute episode is rare but requires adequate
      management. Aim of this study is to evaluate the health care needs of these
      patients vs patients with exclusively acute disease and to underline the need of
      identifying criteria for health care taking into account basic clinical
      conditions. This study can be carried out most suitably at the Gaslini Institute,
      since it is a children's hospital with a Pediatric Emergency Department admitting
      children from the Liguria region presenting almost the whole range of chronic
      pediatric diseases.

PMID- 14601234
TI  - [Long-term treatment with cabergoline in pregnancy and neonatal outcome: report
      of a clinical case].
AB  - Hyperprolactinemia is one of the causes of sterility. Cabergoline is indicated in
      cases resistant to bromocriptine, but, usually, its administration is interrupted
      at the beginning of the pregnancy. A case of prolonged treatment with cabergoline
      during pregnancy is reported, without teratogenic effects on the fetus.

PMID- 14601235
TI  - [Periodic fever, aphthous stomatitis, pharyngitis, and lymphadenopathy: a
      pediatric caseload].
AB  - We report 5 patients (3F; 2M; age 19-60 months) affected by a syndrome
      characterized by recurrent episodes of abrupt onset of fever, aphtous stomatitis,
      pharyngitis and cervical adenopathy named by the acronym PFAPA (periodic fever,
      aphtous stomatitis, pharyngitis and adenopathy). The episodes had clockwork
      periodicity (3-4 weeks) and the fever was unaccompanied by remarkable respiratory
      signs or symptoms. All children were doing well between episodes. The
      inflammatory markers were elevated only during attacks in all children. Steroid
      therapy was highly effective in controlling symptoms in 5/5 patients and
      tonsillectomy was associated with remission in two of five patients. In one child
      the syndrome resolved spontaneously, in two patients resolved after tonsillectomy
      and in two children persisted. No long-term sequelae were observed.

PMID- 14601236
TI  - Bilateral neonatal adrenal abscess. Report of two cases and review of the
      literature.
AB  - Neonatal adrenal abscess is an extremely rare condition. 32 cases, 4 bilateral,
      have been described in the world literature. We treated successfully other two
      bilateral cases. We report on this rare condition and review the world
      literature. In our Department we observed two patients in the neonatal period
      with abdominal distension, vomiting, irritability and fever. Abdominal ultrasound
      (US), plain x-ray of the abdomen, intravenous pyelography and computed tomography
      (CT) of the abdomen were performed. In both cases bilateral suprarenal cystic
      masses were identified. Vanilmandelic acid, Homovanillic acid and cathecolamines
      were normal. The two neonates underwent a surgical exploration. Abscesses were
      found and drained releasing a moderate amount of haemorrhagic and purulent
      materials from the adrenal glands. Post-operative histology on the surgical
      specimen showed in both cases an abscess in partial haemorrhagic adrenal glands.
      No neoplastic cells were observed. The recovery was uneventful and at six months
      follow-up both patients were well and without signs of adrenal insufficiency.
      Haematogenous bacteria seeding a normal gland or abscess formation in a previous
      haemorrhagic gland are the most accredited theories. Neuroblastoma, Wilm's tumor
      and renal duplication with dilatation of the upper segment must be considered in
      the differential diagnosis. Percutaneous drainage (+/- biopsy) under CT or US
      guide should be considered the treatment of choice, followed by surgical
      exploration when diagnosis is not clear.

PMID- 14601237
TI  - [Guidelines in neonatology].

PMID- 14601238
TI  - [Resuscitation in the delivery room: new guidelines].

PMID- 14601239
TI  - [Management of newborns with congenital malformations].

PMID- 14601240
TI  - [Guidelines and prognostic value of cerebral echography].

PMID- 14601241
TI  - [Neurologic prognosis based on movements and postures].

PMID- 14601242
TI  - [Streptococcus agalactiae].

PMID- 14601243
TI  - [Congenital toxoplasmosis].

PMID- 14601244
TI  - [Congenital toxoplasmosis: laboratory diagnosis].

PMID- 14601245
TI  - [Management of children born from mothers with HIV infection].

PMID- 14601246
TI  - [Vaccination of preterm infants].

PMID- 14601247
TI  - [Various legal features of the medical profession].

PMID- 14601248
TI  - [Methods for measuring the protein glycation products formed in the human
      organism].
AB  - The advanced glycation end-products (AGEs) are the compounds formed and
      accumulated in the organism. There is heterogenous group of the glycation
      products, which have great variety of structural and functional properties. The
      glycation end-products can be used as markers of the glycation process. Because
      of the great heterogeneity of the AGEs there is no specific test for their
      adequate measurement. In this paper there are presented the chromatographic,
      colorimetric, spectroscopic, mass-spectrometric and serological methods, which
      are used for determination of AGEs in biological samples. New procedures for the
      preparation of the model AGEs have been also described. Special attention has
      been paid to the immunochemical tests. For further assays the model AGE antigens
      have to be prepared.

PMID- 14601249
TI  - [Notch1 receptor: structure and role during T-cell development].
AB  - The Notch family are proteins which function both as cell surface receptors and
      regulators of gene transcription. Notch proteins influence cell-fate decisions
      during lymphopoesis, neurogenesis and myogenesis. During lymphopoesis Notch1 is
      implicated in differentiation of lymphoid precursor CLP towards T-cells bot not B
      cells lineage. In spite of earlier results suggesting involvement of Notch1 in
      commitment towards alpha beta and gamma delta or CD4 and CD8 T cell lineage,
      later experiments didn't confirm this possibility.

PMID- 14601250
TI  - [Role of lactoferrin in development of inflammation].
AB  - During acute inflammation, immune homeostasis is lost leading to destructive
      immunopathology. Homeostasis is normally dependent upon coordinated interactions
      among the various lymphoid, phagocytic and somatic cells that comprise the immune
      system. In general, these interactions are tightly regulated to obtain a balance
      between mechanisms necessary to eliminate harmful pathogens, and overaggressive
      responses leading to destruction of host tissue. Activation of immunoeffector
      cells results in pro-inflammatory cytokine up-regulation which in turn also
      activates the vascular endothelium. Through complex signaling, a positive
      feedback circuit is established which amplifies and sustains the activity of the
      inflammatory response resulting in the release of other cytokines and related
      molecules. If these responses are activated in an uncontrolled fashion with
      dissemination via the circulation, over the period of time, organs distant from
      the initial insult can be affected to produce multiple organ failure.
      Lactoferrin, an iron-binding glycoprotein, is considered an important mediator in
      host defense against the environmental insults in mammals. By virtue of iron
      sequestration lactoferrin can control the development of many oxidative stress
      driven responses. The purpose of this review is to provide a comprehensive
      summary of research regarding lactoferrin and its role in homeostasis.

PMID- 14601251
TI  - [The role of immunologic response in chronic allograft rejection].
AB  - Chronic allograft rejection is an active immunologic and inflammatory process
      leading to graft failure. It is associated with many disorders evidencing
      increased reactivity of the host against graft alloantigens. Among the most
      important ones are: de novo synthesis of antibodies against HLA class I and II,
      immunoglobin deposits on vascular endothelial and tubular basement membrane, C4d
      complement deposits in peritubular capillaries, increased proliferation of
      lymphocytes in response to mismatched HLA-DR, and elevated expression of
      cytokines on infiltrating mononuclears and tubular cells. Prevention of chronic
      rejection comprises of transplanting undamaged organs, avoidance of acute
      rejection, incorporation of medicines inhibiting remodelling of vascular wall
      into therapy, and elimination of factors accelerating graft damage. In case of
      humoral chronic rejection suppression of humoral arm immune response is required.
      Early diagnosis and effective suppression of antibody production may allow to
      avoid progression of allograft failure.

PMID- 14601252
TI  - [Congenital disorders of glycosylation].
AB  - Congenital disorders of glycosylation are group of hereditary diseases resulting
      in severe psychomotor retardation and multiorgan failure. So far eleven different
      defects were identified on the pathway of N-glycan biosynthesis. Seven of them
      belong to CDG type I and result in incomplete occupation of potential N
      glycosylation sites. Four defects were found in N-glycan processing. Molecular
      background of CDG and potential perspectives of therapy are summarised and
      updated in this review.

PMID- 14601253
TI  - [The influence of hypoxia on blood vessels endothelial cell function in brain].
AB  - Regardless of reason, endothelial cells hypoxia is a primary source of their
      dysfunction. The result of hypoxia is a damage of endothelium structure, that
      leads to neurons damage. Parallel to the hypoxia, the protective mechanisms are
      activated in order to decrease effect of endothelium and neurons damage.

PMID- 14601254
TI  - Message from the president of the WAPM. Perinatal problems in developing
      countries--lessons learned and future activities.

PMID- 14601255
TI  - Antalya consensus on perinatal care: the report of the 2nd World Congress of
      Perinatal Medicine for Developing Countries, 1-5 October 2002, Antalya, Turkey.
AB  - The goal of antenatal care is to help the mother to maintain her well-being and
      achieve a healthy outcome for herself and her infant. Education about pregnancy,
      child-bearing and childrearing is an important part of antenatal care. Because of
      the perception that pregnancy is a physiologic event, even today lots of women do
      not seek medical care until a problem occurs during their pregnancy. There are
      still unacceptable differences in the extent of perinatal problems in developed
      and developing countries. Over the last century almost all countries have
      accepted antenatal care principles. However, insufficiency of resources and a
      lack of women's compliance have proved to be obstacles in developing countries
      and have compelled the application of various standard programs. Unfortunately,
      these programs are not sufficiently effective in preventing and treating maternal
      mortality. A safe pregnancy and delivery is a human right. Maternal mortality and
      morbidity should not be ranked with other diseases, because child bearing is not
      a disease. For this reason a global ethical consideration imposes an obligation
      upon society to avoid these almost totally preventable deaths. Ensuring access to
      family planning is an important way of decreasing maternal death. Maternal
      morbidity and mortality as well as perinatal mortality can be reduced through the
      synergistic effect of combined interventions, without first attaining high levels
      of economic development. These interventions include: education for all,
      universal childbirth, access to family planning services, attendance at birth by
      professional health workers, access to good quality care in case of
      complications, and policies that raise women's social and economic status and
      increase their access to property and the labor force.

PMID- 14601256
TI  - Reduction in mortality needs a bit more than the science of perinatology.
AB  - The absence or non-availability of medical centers with inaccessible distance and
      delay in providing treatment is an insurmountable problem in backward regions. A
      pregnant mother from a developing country is 30 times more likely to die than a
      mother from a developed country and her newborn faces the same risk of mortality.
      The involvement of government is a vital part of the attempt to achieve
      improvements. Government has the power and obstetricians have the information to
      lead the way. No doubt even when the two cooperate there is still room for
      inadequacy, but perhaps partners like the WHO, UNFPA, UNICEF, IPPF, FIGO, World
      Bank, World Association of Perinatal Medicine, World Pediatric Association,
      International Midwives Confederation, etc. can help to achieve targets. There is
      urgent need for the twinning of the perinatal departments of developing countries
      with the perinatal departments of advanced countries and/or the twinning of
      countries or geographical areas, or of NGOs with government and change in
      mindsets where required. To obtain the maximum benefits from such an approach, it
      would be necessary to go a little beyond perinatal science.

PMID- 14601257
TI  - Global, regional and national perinatal and neonatal mortality.
AB  - Globally, the perinatal mortality rate (PMR) is 53/1000 (7.5 million annual
      perinatal deaths) and the neonatal mortality rate (NMR) is 36/1000 (5.1 million
      annual neonatal deaths). Of the 141 million annual livebirths, 127 million (90%)
      are born in developing countries, which, compared to developed countries, have a
      higher PMR (57/1000 vs 11/1000, 5.2x) and NMR (39/1000 vs 7/1000, 5.6x). Five
      million annual neonatal deaths (98% of the world's total) occur in developing
      countries. Regional annual livebirths figures are: Asia-Oceania 76 million,
      Africa 31 million, Central and South America 12 million, Europe 8 million, and
      North America 4 million. Regional annual neonatal death figures are: Asia-Oceania
      3.3 million, Africa 1.3 million, Central and South America 0.3 million, Europe
      0.07 million, North America 0.03 million. The Asia-Oceania region has a PMR of
      53/1000 and a NMR of 41/1000. It has half of the world's livebirths and two
      thirds of the world's neonatal deaths. The PMR and NMR have often been used as an
      indicator of the standard of a country's social, educational and healthcare
      systems. Strategies, which address inequalities both within a country and between
      countries, are necessary if there is going to be further improvement in global
      perinatal health.

PMID- 14601258
TI  - Maternal mortality in Turkey.
AB  - All maternal deaths are considered as a social injustice. For this reason,
      governments should take necessary measures to make motherhood safer. In order to
      prevent premature deaths of women, causes of deaths must be known. In Turkey, the
      latest survey conducted in hospitals in selected 53 provinces. This hospital
      based survey revealed that maternal mortalities make up 5% of all women deaths
      and maternal mortality is 49.2 per hundred thousand live births. Factors which
      are related with the status of women including, education, socio-economic
      conditions, early marriage age, and fertility level have influence on maternal
      mortality level in the community. Accessibility and availability of maternal
      health care services are also very important factors to reduce maternal
      mortality.

PMID- 14601259
TI  - Maternal mortality in developing countries.
AB  - Of all health statistics mentioned by the World Health Organization (WHO),
      maternal mortality is unique in showing the largest discrepancy between developed
      and developing countries. Approximately 90% of maternal deaths (more than 0.5
      million each year) occur in developing countries. Over the last century, almost
      all countries have accepted antenatal care principles. However, insufficiency of
      resources and lack of women's compliance were the main handicaps in developing
      countries and compelled these countries to apply various standard programs.
      Unfortunately, these programs are not sufficiently effective in the prevention
      and treatment of maternal mortality. Fixing the number (quantity) of antenatal
      visits and the static approach affect the "quality" of antenatal care. Bleeding,
      chronic anemia, hypertensive disorders, obstructed labor, unsafe abortions and
      infections are the main factors leading to maternal mortality. The majority of
      these factors are preventable. It is important to suspect the presence of any of
      these factors and to intervene promptly both during antenatal care and
      immediately after delivery. The evidence-based approach is a way of reaching this
      solution. Antenatal care is a concept that extends from pre-pregnancy to
      postpartum, leading to effective emergency care for unpredictable and predictable
      complications during pregnancy and childbirth. Worldwide policies are not always
      applicable to each country, coercing national policies. There is still a need for
      prospective randomized trials to clarify this concept and the relevant policies.

PMID- 14601260
TI  - Organization of neonatal care services and its importance.
AB  - Universally 4 million newborns die and another 4 million are stillborn every
      year. 98% of these neonatal deaths take place in the developing countries.
      Looking at the state of the world's newborns one can see that neonatal mortality
      rate is about 4-5 per 1000 in the developed countries and nearly 10 fold this in
      the developing world. Causes that underlie these newborn deaths differ according
      to a country's development rank. According to the WHO estimates for the year
      2001, newborns die due to infections (32%), birth asphyxia and trauma (29%),
      prematurity (24%) and congenital anomalies (10%), mostly in the developing
      countries. When organizing neonatal care services in a country or a region,
      priorities should be decided by looking at neonatal and perinatal mortality rates
      and causes of neonatal and perinatal deaths. Causes of neonatal and perinatal
      deaths in the developing countries have been documented and reflect some common
      underlying problems in the health systems. Starting points in the organization of
      neonatal health care services seem to include: improving women's health and
      social status, family planning practices, antenatal care and safe delivery
      conditions. Attention should also be paid to neonatal resuscitation, essential
      newborn care and sick newborn care practices. Communities and health
      professionals should be advocates of newborn health in order to seek and deliver
      newborn health care. Existing health systems should be re-organized to host
      regionalized perinatal care.

PMID- 14601261
TI  - The Misgav Ladach method--a step forward in operative technique in obstetrics.
AB  - AIM: To investigate the advantage of performing cesarean section using the Misgav
      Ladach method and to justify its use in everyday practice. METHODS: In a
      prospective study we analyzed over a two year period (2000-01) cesarean sections
      carried out using the Misgav-Ladach method at our clinic. We compared both 550
      cases of Misgav-Ladach (ML) and 100 cases of Pfannenstiel (PH) cesarean section.
      In the group that had undergone the Misgav-Ladach method we sutured the uterus in
      one layer and left the peritoneum non-sutured, and in the group who had undergone
      Pfennenstiel we sutured the uterus in two layers and also sutured the visceral
      and parietal peritoneum. In every case we analyzed: maternal age, gestational
      age, duration of operation, consumption of suture material, duration of
      hospitalization, and surgical complications. RESULTS: Incidence of postoperative
      febrile morbidity was 5.45%, in the Misgav-Ladach group compared with 13.2% in
      the Pfannenstiel group (p < 0.05). Local infection of the wound in the Misgav
      Ladach group was found in 4.54% and in the Pfannenstiel group in 9% (p < 0.05).
      Mean time of extraction of the newborn in the Misgav-Ladach group was 1.25
      minutes, and in the Pfannenstiel group 4.10 minutes (P < 0.05). Mean duration of
      operation in the Misgav-Ladach group was 10.98 min, and in the Pfannenstiel group
      25 min (p < 0.05). Mean duration of hospitalization in the Misgav-Ladach group
      was 4.75 days, and in the Pfannenstiel group 6.32 days (p > 0.05). Mean
      consumption of suture material in the group Misgav-Ladach was 3.10 sutures per
      operation, and in the Pfannenstiel group was 9.5 sutures. CONCLUSION: Our study
      shows that the Misgav-Ladach method of cesarean section enables fast recovery and
      shorter hospitalization, and reduces the length of the operation, the incidence
      of surgical complication and the consumption of surgical materials.

PMID- 14601262
TI  - Monitoring the IUGR fetus.
AB  - Monitoring of the intrauterine growth retarded fetus in order to improve fetal
      outcome and define precisely the timing of delivery, when necessary, is based on
      the study of changes in vital functions observable in cases of hypoxemia. It is
      easy to believe that ultrasound equipment with Doppler facilities is present in
      the majority if not in all gynecological units. Cardiotocography is also widely
      used and the addition of a computerized evaluation system is not expensive and
      therefore should be available when facing high risk pregnancies such as
      intrauterine growth retarded cases. IUGR can be recognized through the use of
      ultrasound fetal biometry and clinical examination of maternal conditions in
      order to assess fetal conditions. If the above technologies are available further
      action, such as fetal Doppler study of fetal vessels and cardiotocography, can
      then be undertaken. In this paper, we will be discussing the issue of monitoring
      the fetus for fetal well-being, particularly in cases of intrauterine growth
      retarded fetuses.

PMID- 14601263
TI  - Massive obstetric hemorrhage.
AB  - Massive obstetric haemorrhage is a major cause of maternal death and morbidity;
      abruption of the placenta, placenta praevia and postpartum haemorrhage being the
      main causes of haemorrhages. A delay in the correction of hypovolaemia, diagnosis
      and treatment of defective coagulation and/or surgical control of bleeding are
      the avoidable factors in most maternal deaths caused by haemorrhage. The main
      goal is to maintain effective circulating intravascular volume by prompt and
      adequate replacement of blood, crystalloids or fresh-frozen plasma through more
      than one intravenous line (it might be necessary to pump blood under pressure)
      with constant monitoring of the pulse rate and the arterial blood pressure. The
      rapid correction of hypovolaemia with crystalloids and red cells is the first
      priority, followed by blood component therapy. Oxytocin and prostaglandin will
      correct uterine atony, and appropriate surgical intervention is required for
      traumatic bleeding. Ligation of the uterine arteries, ovarian arteries and
      hypogastric arteries will usually control uterine bleeding and arterial
      embolization is also effective. Hysterectomy should also be considered in severe
      cases. All gynecologists should be able to perform without delay the operative
      maneuvers which are necessary to control the bleeding, including hypogastric
      artery ligation, or even emergency hysterectomy. This topic may have received
      little attention because it is perceived as being associated with maternal
      morbidity rather than mortality in developed countries; it is only recently that
      the extent and importance of postnatal maternal morbidity has been recognized.

PMID- 14601264
TI  - Breech deliveries and cesarean section.
AB  - Breech presentation is the most common malpresentation, with about 3-4% of
      singleton fetuses presenting breech at delivery. Management of breech
      presentation has been a contentious issue with a lowering threshold for cesarean
      section in recent years. Perinatal mortality and morbidity are estimated to be
      three times that of comparable infants with vertex presentation. Breech
      presentation is commonly associated with certain adverse maternal and fetal
      factors which inherently give rise to increased perinatal morbidity and
      mortality. At present, most obstetricians favor cesarean delivery for
      uncomplicated pre-term breech. Controlled prospective studies have shown that the
      outcome of breech fetuses weighing more than 1500 g was not dependent on the mode
      of delivery. A more recent review from the Cochrane database by Grant does not
      justify a policy of elective cesarean section for pre-term breech. Vaginal
      delivery is preferred if the following criteria are met: frank breech only,
      estimated fetal weight of 2500-3500 g, adequate pelvimetry without hyperextended
      head, normal progression of labor, no evidence of fetal hypoxia under continuous
      fetal monitoring, and maternal weight under 90 kg. Vaginal delivery of frank
      breech at term may be just as safe as cesarean section when careful selection
      criteria are used. If these criteria are not fulfilled, or fetal monitoring
      cannot be performed, cesarean section is advisable.

PMID- 14601265
TI  - Iron supplementation in pregnancy.
AB  - Iron deficiency is the most common nutritional disorder in the world. Pregnant
      women are at especially high risk for iron deficiency and iron deficiency anemia.
      A considerable proportion of pregnant women in both developing and industrialized
      countries become anemic during pregnancy. The prevalence of anemia in pregnant
      women has remained unacceptably high worldwide despite the fact that routine iron
      supplementation during pregnancy has been almost universally recommended to
      prevent maternal anemia, especially in developing countries over the past 30
      years. The major problem with iron supplementation during pregnancy is
      compliance. Despite many studies, the relationship between maternal anemia and
      adverse pregnancy outcome is unclear. However, there is now sufficient evidence
      that iron supplements increase hemoglobin and serum ferritin levels during
      pregnancy and also improve the maternal iron status in the puerperium, even in
      women who enter pregnancy with adequate iron stores. Recent information also
      suggests an association between maternal iron status in pregnancy and the iron
      status of infants postpartum. The necessity of routine iron supplementation
      during pregnancy has been debated in industrialized countries and routine
      supplementation is not universally practiced in all these countries. In view of
      existing data, however, routine iron supplementation during pregnancy seems to be
      a safe strategy to prevent maternal anemia in developing countries, where
      traditional diets provide inadequate iron and where malaria and other infections
      causing increased losses are endemic.

PMID- 14601266
TI  - Antenatal diagnosis and prognosis of conjoined twins--a case report.
AB  - In this report, two conjoined twin cases that were diagnosed at the 19th and 25th
      week of gestational age are reported. In the first case the pregnancy was
      terminated because of the very poor prognosis. In the second case the decision
      was made to continue the pregnancy after counseling explaining the possibility of
      a separation procedure with good prognosis being carried out after birth. The
      babies were delivered at 38 weeks of gestation and the separation procedure was
      carried out at ten months of age without any complications. In selected cases,
      there is no need to abort, because of the possibility of a separation procedure
      after birth with good prognosis. Color Doppler ultrasound examination in an early
      stage of pregnancy in cases of conjoined twin can make it possible to decide
      which cases are candidates for a separation procedure after birth.

PMID- 14601267
TI  - Preliminary report on a new and noninvasive method for the assessment of fetal
      lung maturity.
AB  - OBJECT: Several patterns of fetal breathing movements (FBMs), i.e. abdominal wall
      movements (AWm), thoracic wall movements (TWm) and nasal fluid flow velocity
      waveforms (NFFVW), were investigated by ultrasound (US) technology and related to
      fetal pulmonary maturity and immaturity, i.e. fetal lung maturity (FLM) tests, in
      order to validate the hypothesis that they may indicate whether the fetal lung is
      mature or immature, regardless of gender, weight and gestational age. MATERIAL
      AND METHODS: We prospectively enrolled 143 high-risk pregnancies in which a
      complete US study of FBMs and FLM tests was performed. Among them 43 women
      satisfied the inclusion criteria. US-FLM was defined as the presence of regular
      NFFVW detected by pulsed Doppler and spectral analysis, or irregular NF-FVW
      synchronous with TWm detected by M-mode. An US guided amniocentesis was performed
      in order to collect amniotic fluid (AF) and FLM was evaluated by L/S
      (lecithin/sphingomyelin) determination, presence of phosphatidylglycerol (PG) and
      lamellar bodies (LBs) count. At the end of the study the diagnostic accuracy of
      US-FLM was compared to that of FLM tests. RESULTS: Diagnostic accuracy for US
      evaluation of FLM was as follows: sensitivity: 89.6%; specificity: 85.7%; PPV:
      92.8%; NPV: 80%. Diagnostic accuracy of FLM tests was as follows: sensitivity:
      100%; specificity: 51.7%; PPV: 100%; NPV: 50%. L/S determination predicted lung
      maturity with a sensitivity of 100%; specificity of 93.1%; PPV of 100%; NPV of
      87.5%. CONCLUSION: Presence of regular NFFVW or irregular NFFVW and TWm correlate
      accurately with conventional FLM tests. We suggest that this noninvasive
      procedure may be helpful for assessing FLM, particularly under certain
      circumstances, e.g., oligo-anhydramnios, laboratory logistic equipment
      difficulties or heavily stained AF samples, amniocentesis refusal, religious
      concerns.

PMID- 14601268
TI  - Perinatal mortality rate--hospital based study during 1998-2001 at Hacettepe
      University.
AB  - AIMS: To determine the causes of perinatal mortality and to calculate perinatal
      mortality rates at Hacettepe University Hospital. MATERIAL AND METHODS: In 1998
      the Perinatal Mortality Study Group was established at Hacettepe University. The
      study group was constituted by the Department of Pediatrics, Units of Pediatric
      Pathology, Pediatric Cardiology, Pediatric Surgery, Genetics and Neonatology and
      the Department of Obstetrics and Gynecology, Perinatology Unit. At the end of
      every month, each case (including autopsy results if available) was discussed
      among the group, and the cause of mortality was determined according to the
      Modified Wigglesworth Classification, by the consensus of the group members.
      Perinatal mortality rates at Hacettepe University were prospectively calculated.
      Perinatal mortality figures of two periods were compared (1998-1999: Group A and
      2000-2001: Group B). RESULTS: Total number of births over 500 grams was 3173 in
      Group A and 3013 in Group B. Perinatal mortality rate was 33.72/1000 in Group A
      and 16.92/1000 in Group B. Of the perinatal deaths, 61.46% were intrauterine
      deaths and 38.54% were early neonatal deaths in Group A. In Group B, 58.83% were
      intrauterine deaths and 40% were early neonatal deaths. In Group A, 72% of the
      deaths were < 1500 grams, and 53.3% were 500-1000 grams. The most common cause of
      death during this period was prematurity (Modified Wigglesworth Group III)
      (29.3%), followed by lethal congenital malformations (Group II) (26.6%) and
      macerated intrauterine deaths (Group I) (22.9%). Autopsy was available in 70.7%
      of the cases and micronecropsy was available in 12%. Genetic studies were
      performed in 24% of the cases and termination of pregnancy was carried out for
      fetal anomalies in 10.7% of the cases. In Group B, 72.6% of the cases were < 1500
      grams and 47.1% of the cases were 500-1000 grams. The most common cause of death
      during this period was lethal congenital malformations (Group II) (31.4%),
      followed by macerated intrauterine deaths (Group I) (21.5%) and specific causes
      (Group V) (21.5%). Autopsy was available in 70.17% of the cases and micronecropsy
      was obtained in 10.52% of the cases. 20% of the cases underwent genetic studies
      during pregnancy and termination of pregnancy was carried out in 19.29% of the
      cases. CONCLUSIONS: Perinatal mortality rate has decreased at Hacettepe
      University over the last two years. The authors believe that this is a result of
      the multidisciplinary work which has had an impact on perinatal and neonatal
      care. The most common cause of mortality has changed from prematurity to lethal
      congenital malformations in this period. Since our institution is a referral
      center, around 60% of mortality is due to intrauterine deaths and around 30% of
      the deaths are due to lethal congenital malformations. Unfortunately lethal
      congenital malformations are referred to our center at an advanced stage of
      pregnancy.

PMID- 14601269
TI  - The effect of glucocorticoid therapy in preventing early neonatal complications
      in preterm delivery.
AB  - AIM: Premature birth is the single largest cause of perinatal mortality and
      morbidity in non-anomalous infants in all developed nations. The aim of this
      study is to survey the role of glucocorticoid therapy in decreasing early
      neonatal complications in preterm delivery. METHODS: A case control study was
      carried out on 300 preterm labors. Half the women received one to four 6 mg doses
      of dexamethasone every 6 hours, depending on the interval between admission and
      delivery. Neonatal complications were compared between the two groups. RESULTS:
      Corticosteroid therapy was observed to have the greatest effect in preventing
      respiratory distress and neonatal mortality between 29-34 gestational weeks.
      There was a significant relationship between antenatal corticosteroid therapy
      interval and mortality of preterm neonates. Complications such as respiratory
      distress, sepsis, pneumonia, and hyperbilirubinemia were significantly lower in
      the case group than in the control. CONCLUSION: It is recommended that all women
      at high risk for preterm labor before 35 gestational weeks be given
      glucocorticoid at least 24 hours before delivery in order to markedly reduce
      neonatal mortality and morbidity.

PMID- 14601270
TI  - Local anaesthesia--early spinal anaesthesia.

PMID- 14601271
TI  - Legal aspects of withdrawal of therapy.
AB  - The ability of intensive care to replace or support vital organ function has
      resulted in some patients surviving for long periods of time without improvement
      or a terminal event. In patients with no realistic chance of survival, decisions
      to withdraw or withhold life-sustaining therapies are commonly made. Withdrawal
      of life support at the patient's request is lawful at common law and, in some
      states of Australia, by legal statute. In the intensive care setting though, it
      is more common for therapy to be withdrawn because the therapy is of no perceived
      benefit or not in the patient's best interests. However, in Australia there is
      little case law and very little legislation to direct the decision of whether to
      withdraw life-sustaining therapy on the grounds of futility or the patient's best
      interests. The legislation that does exist in Australia, as well as law from
      other jurisdictions, largely places responsibility for the decision to withdraw
      therapy on the doctor in charge of the patient's care. However much weight is
      frequently placed on the wishes of the family. Disagreements between family and
      clinicians over decisions to withdraw therapy are unusual and generally resolve
      over time. However if disagreement persists, it may be advisable to apply to the
      courts for a declaratory judgement, given the tenuous legal basis of withdrawal
      of life-sustaining therapy in Australia and the uncertainty over the courts' view
      of the role of the patient's family in the decision-making process.

PMID- 14601272
TI  - Withholding and withdrawal of therapy in patients with acute renal injury: a
      retrospective cohort study.
AB  - The incidence of withholding and withdrawal of therapy in the setting of multi
      organ failure in critically ill patients has increased. Epidemiological data on
      the decision-making process of withholding or withdrawal of therapy from
      Australian and New Zealand intensive care units is sparse. We examined the
      clinical and electronic records of 179 consecutive patients, admitted to the ICU
      between 1st January 2000 and 31st December 2001, who had acute renal injury.
      Acute renal replacement therapy was offered in 11.2% of patients. Therapy was
      withheld or withdrawn in 21.2% of patients. The levels of supportive care were
      comparable between those who had therapy withheld or withdrawn and those who had
      full intensive care therapy until such a decision was made. Predicted mortality
      (OR 1.04, 95% CI: 1.01-1.08, P = 0.03) and age (OR 1.04, 95% CI: 1.00-1.08, P =
      0.03) were independently associated with the decision to withhold or withdraw
      therapy. The mean ICU stay of those with withdrawal or withholding of therapy was
      much shorter than those with full therapy (2.5 vs 5.7 days). This was likely to
      be due to an older age of our cohort, rapid progressive nature of the acute
      disease, a different clinical approach to treating critically ill elderly
      patients, or a combination of these factors. This pattern of practice was quite
      different from those reported from ICUs in other parts of the world. A
      prospective multi-centre observational study will clarify the pattern of practice
      in this important area of intensive care practice in Australasia.

PMID- 14601274
TI  - Epidural catheter migration: a comparison of tunnelling against a new technique
      of catheter fixation.
AB  - We investigated the efficacy of a new technique of epidural catheter fixation
      that relies on a strip of adhesive foam transfixed by a securing suture. We
      compared this technique to a tunnelled technique in a prospective, randomized
      trial (n = 25 in each group). Epidural catheter depth was recorded at the time of
      insertion and at the time of removal. Clinically significant catheter movement
      was considered as > 2 cm outward movement or > 1 cm inward movement. The mean
      duration of epidural analgesia was five days for both groups. Clinically
      significant movement was noted in eight patients (32%) in the tunnelled group and
      seven patients (28%) in the sutured group (P = 0.75). Movement of the epidural
      catheter did not correlate with analgesic failure. The sutured technique provided
      similar protection against migration to tunnelling but any potential advantages
      were offset by concerns about a significantly higher incidence of erythema around
      the catheter exist site in the sutured group (1 vs 6 patients, P = 0.04).

PMID- 14601273
TI  - Paraesthesiae during needle-through-needle combined spinal epidural versus single
      shot spinal for elective caesarean section.
AB  - The aim of this study was to compare the incidence of paraesthesiae during spinal
      needle insertion in a needle-through-needle combined spinal-epidural (CSE) versus
      a single-shot spinal (SSS) technique. Eighty-nine women presenting for elective
      caesarean section at a tertiary referral obstetric unit were randomized to
      receive either needle-through-needle CSE or SSS. Equipment used was a 16 gauge/26
      gauge combined spinal-epidural kit and a 26 gauge pencil-point spinal needle with
      introducer (both Sims Portex, Australia) The presence and distribution of
      paraesthesiae was recorded by an observer at spinal needle insertion and again on
      day one postoperatively. There were three failures to perform the intended block.
      One patient was lost to follow-up at postoperative day one. Seventeen of forty
      six (37%) women in the needle-through-needle CSE group and four of forty-three
      (9%) in the SSS group had paraesthesiae upon spinal needle insertion (P < 0.05,
      Chi-squared test). No patient had persistent neurological symptoms at
      postoperative day one. We postulate that the higher incidence of paraesthesiae
      with needle-through-needle CSE may be related to deeper penetration of the
      subarachnoid space with this technique.

PMID- 14601275
TI  - Correlation and linear regression between blood pressure decreases after a test
      dose injection of propofol and that following anaesthesia induction.
AB  - Propofol reduces systemic vascular resistance and suppresses cardiac function
      when injected rapidly. In this study we investigated whether blood pressure
      decrease after a minimal dose (test-dose) injection of propofol correlates with
      that after an induction-dose injection. Patients were randomly divided into two
      groups; anaesthesia was induced in group A (n = 60) using 1.5 mg/kg propofol and
      in group B (n = 61) using 2.0 mg/kg. Blood pressure reduction after a minimal
      dose injection (0.4 mg/kg) was examined non-invasively prior to anaesthetic
      induction. Bispectral Index monitoring was measured and sedation level scored to
      evaluate anaesthetic depth. After the minimal dose injection, 18 of 121 patients
      showed behaviour suggesting minor disinhibition, five patients were sedated and
      seven were drowsy. Oxygen saturation was not significantly changed after test
      dose injection. Reduction in systolic blood pressure (mean +/- SD) was 17 +/- 11
      mmHg after the minimal dose injection, 42 +/- 20 mmHg after a 1.5 mg/kg induction
      dose injection, and 42 +/- 22 mmHg after a 2.0 mg/kg induction-dose injection. In
      both groups, blood pressure after induction was significantly lower than the
      control value (P < 0.05). In both groups, a positive correlation was observed
      between blood pressure reduction after the minimal dose injection and that after
      the induction-dose injection [P < 0.01, R value for systolic blood pressure
      correlation in group A 0.712 (P < 0.01) and in group B 0.758 (P < 0.01)]. We
      concluded there was a positive correlation between blood pressure reduction after
      a minimal (test-dose) injection and that after an induction-dose injection.

PMID- 14601276
TI  - Use of intravenous tranexamic acid to reduce allogeneic blood transfusion in
      total hip and knee arthroplasty: a meta-analysis.
AB  - Total hip or knee arthroplasty is associated with significant blood loss.
      Techniques such as the use of antifibrinolytics or desmopressin, or normovolaemic
      haemodilution have been used to reduce the need for allogeneic blood transfusion.
      Tranexamic acid has been used to reduce blood loss and transfusion requirement
      for total hip and knee arthroplasty, with variable results. This meta-analysis
      aims to evaluate whether intravenous tranexamic acid, when compared with placebo,
      reduces blood loss and transfusion requirement in total hip and knee joint
      replacement surgery and whether it might increase the risk of thromboembolic
      complications. The literature search was based on MEDLINE, EMBASE, Cochrane
      Controlled Trials Register, and information from the pharmaceutical company that
      produces tranexamic acid (Pharmacia-Upjohn). We identified 15 clinical trials and
      12 were considered suitable for detailed data extraction. Tranexamic acid reduces
      the proportion of patients requiring allogeneic blood transfusion (OR 0.16, 95%
      CI: 0.09-0.26), total amount of blood loss (WMD 460 ml, 95% CI: 274-626 ml), and
      the total number of units of allogeneic blood transfused (WMD 0.85 unit, 95% CI:
      0.36-1.33). Tranexamic acid does not increase the risk of thromboembolic
      complications such as deep vein thrombosis, pulmonary embolism, thrombotic
      cerebral vascular accident, or myocardial infarction (OR 0.98, 95% CI: 0.45
      2.12). Intravenous tranexamic acid appears effective and safe in reducing
      allogeneic blood transfusion and blood loss in total hip and knee arthroplasty.

PMID- 14601277
TI  - An easy method of mentally estimating the metabolic component of acid/base
      balance using the Fencl-Stewart approach.
AB  - The Stewart approach defines acid/base abnormalities as resulting from changes in
      PCO2, strong ion difference (SID), and weak acids (mainly albumin) but needs a
      computer for calculation. The base excess (BE) is a measure of the net effect of
      changes in SID and weak acids, therefore, metabolic acid/base balance can be
      described as BE effects of their change from normal. We compared our mental
      estimation of BE effects with the more complex calculation. Acid/base
      abnormalities were identified in 44 critically ill patients. The BE effects of
      change in strong ions, change in albumin, and the BE-gap ("other species" or
      unmeasured anion effect) were calculated using standard equations. An estimate of
      the BE effects was determined. The difference between SID (using [Na+] + [K+] -
      ([Cl-] + lactate)) and normal SID (42 mEq/l) estimated the effect of a change in
      SID. The effect of a change of albumin from normal was estimated as 0.25 x
      (normal albumin-measured albumin). The predicted BE was defined as estimated
      change in SID plus albumin effect. The estimated BE-gap (BE-gap(est)) was actual
      BE minus predicted BE. The Bland-Altman method was used to test agreement.
      Calculations were made on 46 data sets from 44 individuals. The bias (limits of
      agreement) for calculated and estimated strong ion effects, calculated and
      estimated albumin effect, and calculated and estimated BE-gap were -1.26 (-3.14
      to 0.66) mEq/l, 0.5 (-0.05 to 1.05) mEq/l, and 0.76 (-1.27 to 2.79) mEq/l
      respectively. However the bias (limits of agreement) for BE-gap and BE-gap(est)
      and strong ion gap were poor, being 1.1 (-4 to 14) mEq/l and 0.4 (-9.2 to 10)
      mEq/l respectively. The BE-gap and BE-gap(est) are unsuitable to quantify gap
      ions. However, our easy-to-perform estimation has a clinically acceptable bias
      compared to calculated BE effects and is a simple method for identifying the
      components of acid/base abnormalities.

PMID- 14601279
TI  - Incident reporting in anaesthesia: a survey of practice in New Zealand.
AB  - A postal survey of anaesthetists practising in New Zealand assessed their
      practice and attitudes to anaesthetic incident reporting. 136 replies were
      received (57% response rate). Respondents indicated a high awareness of the
      Anaesthetic Incident Monitoring Study (AIMS) based incident monitoring yet
      individual utilization may be declining due to a perception that this system is
      ineffective. Seventy-five per cent of respondents used AIMS forms in their
      current institute, whilst 87% had at some time completed an AIMS form. Two-thirds
      of respondents used the forms for morbidity and mortality audit activities.
      Support for the continuing practice of incident reporting was high, yet opinion
      suggested that the present system was not being used productively. Almost half
      the anaesthetists felt that the AIMS reporting system had changed their practice.
      Common concerns with the system included a need to simplify the reporting process
      and to ensure that information is managed to provide a useful outcome. This study
      suggests that incident reporting in its present form needs to be re-evaluated in
      light of changing priorities in anaesthesia quality improvement activities.

PMID- 14601278
TI  - Outcome prediction in a surgical ICU using automatically calculated SAPS II
      scores.
AB  - The objective of this study was to establish a complete computerized calculation
      of the Simplified Acute Physiology Score (SAPS) II within 24 hours after
      admission to a surgical intensive care unit (ICU) based only on routine data
      recorded with a patient data management system (PDMS) without any additional
      manual data entry. Score calculation programs were developed using SQL scripts
      (Structured Query Language) to retrospectively compute the SAPS II scores of 524
      patients who stayed in ICU for at least 24 hours between April 1, 1999 and March
      31, 2000 out of the PDMS database. The main outcome measure was survival status
      at ICU discharge. Score evaluation was modified in registering missing data as
      being not pathological and using surrogates of the Glasgow Coma Scale (GCS).
      Computerized score calculation was possible for all investigated patients. The
      459 (87.6%) survivors had a median SAPS II of 28 (interquartile range (IQR) 13)
      whereas the 65 (12.4%) decreased patients had a median score of 43 (IQR 16; P <
      0.001). Of the physiological variables for SAPS II score calculation, bilirubin
      was missing in 84%, followed by PaO2/FiO2 ratio (34%), and neurological status
      (34%). Using neurological diagnoses and examinations as surrogates for the GCS, a
      pathological finding was seen in only 8.8% of all results. The discriminative
      power of the computerized SAPS II checked with a receiver operating
      characteristic (ROC) curve was 0.81 (95% confidence interval (CI): 0.74-0.87).
      The Hosmer-Lemeshow goodness-of-fit statistics showed good calibration (H = 5.55,
      P = 0.59, 7 degrees of freedom; C = 5.55, P = 0.68, 8 degrees of freedom). The
      technique used in this study for complete automatic data sampling of the SAPS II
      score seems to be suitable for predicting mortality rate during stay in a
      surgical ICU. The advantage of the described method is that no additional manual
      data recording is required for score calculation.

PMID- 14601280
TI  - Terlipressin infusion in catecholamine-resistant shock.
AB  - Catecholamine-resistant shock is not uncommon in intensive care. Bolus dose
      terlipressin (a vasopressin analogue) has been used successfully in this setting
      allowing cessation of other vasopressor agents. The relative vasopressin
      deficiency in combination with the restoration of the vascular tone (by blocking
      adenosine triphosphate potassium-sensitive channels) by exogenous vasopressin may
      be the explanation of these beneficial effects. We describe a case report where
      the use of a continuous terlipressin infusion was associated with a dramatic
      improvement. To our knowledge there have been no previous reports of the use of
      terlipressin by continuous infusion for the treatment of catecholamine-resistant
      shock.

PMID- 14601281
TI  - Combined spinal and epidural anaesthesia for caesarean section in a parturient
      with severe primary pulmonary hypertension.
AB  - We describe the management of a parturient with severe primary pulmonary
      hypertension who underwent caesarean section. A multi-disciplinary approach was
      used. She was admitted to the intensive care unit perioperatively for invasive
      monitoring and trial of inhaled nitric oxide. Anaesthesia was provided by
      combined spinal-epidural block. We discuss controversies about the management of
      obstetric patients with this rare and serious condition.

PMID- 14601282
TI  - Inadvertent subdural spread complicating cervical epidural steroid injection with
      local anaesthetic agent.
AB  - Although cervical epidural steroid injection with local anaesthetic is considered
      a safe technique and widely practiced, complications may occur. We report a
      patient experiencing unexpected delayed high block, moderate hypotension and
      unconsciousness eight to ten minutes after an apparently normal cervical epidural
      steroid injection. The most probable diagnosis was a subdural block. Anatomical
      peculiarities of the epidural and subdural space in the cervical region increase
      the risk of subdural spread during cervical epidural injection. Fluoroscopic
      guidance is important during cervical epidural injection to increase certainty of
      correct needle placement, thus minimizing the risk of complications.

PMID- 14601283
TI  - Anaesthetic management of the parturient with protein S deficiency and
      lumboperitoneal shunt.
AB  - Protein S, a vitamin K-dependent plasma protein, is a cofactor for protein C, an
      essential component of the regulatory system of coagulation. We describe the
      anesthetic management of a parturient with protein S deficiency and an indwelling
      lumboperitoneal shunt, which was placed following transverse and sagittal sinus
      thrombosis. She was treated with aspirin and enoxaparin during pregnancy and
      underwent caesarean section under general anaesthesia without complication.

PMID- 14601284
TI  - Subglottic tracheal stenosis in pregnancy: anaesthetic implications.
AB  - We present the first reported case of a pregnant patient with severe subglottic
      tracheal stenosis who required elective surgical tracheostomy prior to
      administration of labour analgesia.

PMID- 14601285
TI  - The Bispectral Index and induced hypothermia--electrocerebral silence at an
      unusually high temperature.
AB  - The optimal temperature for deep hypothermic circulatory arrest remains
      undefined. We present a case in which Bispectral Index monitoring during
      hypothermic cardiopulmonary bypass showed electrocerebral silence at a higher
      temperature than previously reported. Bispectral Index monitoring may be a
      potentially useful tool in surgery employing deep hypothermic circulatory arrest.

PMID- 14601286
TI  - Orthodeoxia--an uncommon presentation following bilateral thoracic sympathectomy.
AB  - We present a case of orthodeoxia (postural hypoxaemia) which resulted from a
      combination of lung collapse/consolidation and blunted hypoxic pulmonary
      vasoconstriction due to partial interruption of the sympathetic nerve supply to
      the lung by bilateral thoracic sympathectomy.

PMID- 14601287
TI  - Failed extubation of a double-lumen tube requiring a cricoid split.
AB  - Following a five-hour procedure, it was not possible to remove a double-lumen
      endobronchial tube that had been placed to facilitate the removal of a massive
      spleen from a 45-year-old female. The tube had been passed easily at the start of
      surgery, but was firmly stuck at the level of the cricoid at the end of surgery.
      Surgical removal of the tube by a cricoid split was required 48 hours later.
      Consideration of previous airway manipulations, careful choice of airway devices
      and regular checks of airway patency around tracheal tubes during lengthy
      procedures may prevent similar events in the future.

PMID- 14601288
TI  - Tracheal rupture following endotracheal intubation.
AB  - We describe a case of tracheal rupture diagnosed after an apparently routine
      endotracheal intubation for otherwise uneventful lower abdominal surgery in a 33
      year-old woman. Risk factors for tracheal rupture, presenting symptoms and signs,
      management of tracheal rupture and methods of airway management during the
      surgical repair of the tracheal laceration are discussed. In this case, "side-by
      side" microlaryngoscopy tubes, one endobronchial and the other with the tip in
      the upper trachea, placed with fibreoptic assistance were used for airway
      management during the tracheal repair.

PMID- 14601289
TI  - Flexi-tip laryngoscope breakage with airway trainer.

PMID- 14601290
TI  - Naltrexone implants.

PMID- 14601291
TI  - Epidural analgesia for patient undergoing hepatectomy.

PMID- 14601292
TI  - A complication of transoesophageal echocardiography in a patient with
      splenomegaly.

PMID- 14601293
TI  - Pain scores in the early postoperative period.

PMID- 14601294
TI  - Anaesthesia for a girl with severe hypertension due to 11 beta-hydroxylase
      deficiency.

PMID- 14601295
TI  - Paediatric day stay tonsillectomy service: development and audit.

PMID- 14601297
TI  - [Electroacupuncture of 2 Hz induces long-term depression of synaptic transmission
      in the spinal dorsal horn in rats with neuropathic pain].
AB  - OBJECTIVE: To observe the effect of 2 Hz electroacupuncture (EA) on long-term
      depression (LTD) of synaptic transmission in the spinal dorsal horn in rats with
      neuropathic pain, so as to explore the central mechanisms of the antinociceptive
      effects of 2 Hz electroacupuncture on neuropathic pain. METHODS: The neuropathic
      pain models were produced by tight ligation of the L5/L6 spinal nerves in Sprague
      Dawley rats. The C-fiber-evoked field potentials in the spinal dorsal horn were
      recorded with extracellular recording techniques. The parameters of the
      electroacupuncture were as follows: frequency of 2 Hz, wavelength of 0.6 ms,
      intensity of 1, 2, 3 mA lasting 10 min for each intensity, stimulation time of 30
      min. The positive stimulating electrode was placed in acupoint "sanyinjiao" and
      the negative electrode in "zusanli". RESULTS: (1) 2 Hz electroacupuncture
      significantly decreased the amplitudes of C-fiber-evoked field potentials in the
      spinal dorsal horn in rats with neuropathic pain to (49.4 +/- 0.6)% of the
      control, compared with that (100.1 +/- 1.2)% of the control before EA (unpaired t
      test, P < 0.001, n = 6), which lasted for at least 3 hours. (2) This EA
      suppression on long-term depression of C-fiber-evoked field potentials in the
      spinal dorsal horn in rats with neuropathic pain could be blocked significantly
      by intravenous application of NMDA receptor antagonist MK-801 (0.5 mg.kg-1), or
      by opioid receptor antagonist naloxone (1 mg.kg-1). CONCLUSION: EA of 2 Hz could
      induce long-term depression of the nociceptive synaptic transmission in the
      spinal dorsal horn in rats with neuropathic pain. This kind of 2 Hz EA
      suppression on LTD was NMDA receptor-dependent and the endogenous opioid system
      may be involved in it. These data indicate that the NMDA receptor-dependent LTD
      at the nociceptive sensory synapses in the spinal dorsal horn in rats with
      neuropathic pain induced by activating the endogenous opioid system may play the
      primary role in the antinociceptive effects of 2 Hz EA on neuropathic pain.

PMID- 14601296
TI  - Effect of 6-OHDA lesions of the dopaminergic mesolimbic system on drug priming
      induced reinstatement of extinguished morphine CPP in rats.
AB  - OBJECTIVE: To evaluate the role played by mesolimbic dopaminergic system in the
      reinstatement of drug-seeking behavior induced by priming injections of morphine.
      METHODS: After the extinguishment of morphine conditioned place preference (CPP),
      low-dose catecholaminergic neurotoxin 6-hydroxydopamine (6-OHDA) was bilaterally
      injected into ventral tegmental area (VTA, 1 g.L-1) and nucleus accumbens (NAc, 5
      g.L-1) before being primed with low-dose morphine. RESULTS: The effects of drug
      priming to induce reinstatement of morphine CPP could be completely abolished by
      6-OHDA microinjected into VTA to damage the perikaryon of dopaminergic neurons,
      or into NAc to lesion the terminal field of the dopaminergic pathway. CONCLUSION:
      The functional integrality of the mesolimbic dopaminergic system is indispensable
      for drug priming-induced reinstatement of conditioned place preference.

PMID- 14601298
TI  - [Electroacupuncture up-regulated arcuate nucleus alpha-MSH expression in the rat
      of diet-induced obesity].
AB  - OBJECTIVE: To investigate the effect of electroacupuncture (EA) on rat with diet
      induced obesity (DIO) and to explore the possible neurochemical mechanisms using
      the technique of immumohistochemistry. METHODS: To establish DIO rat model by
      feeding the animals with high fat diet for 14 weeks. DIO rats were randomly
      divided into 4 groups: (1) 2Hz EA group, (2) 100Hz EA group, (3) restrain control
      group, (4) diet resistance (DR) group, (5) DIO group and (6) normal control
      group. EA treatment: (1) The acupoints used were Zusanli and Sanyinjiao on both
      legs. (2) The intensities of stimulation were 0.5, 1.0 and 1.5mA for 10 mins
      each. EA treatment was administered 3 times per week. Food intake and body weight
      were measured daily for 4 weeks. (3) The changes of the expression of alpha
      melanocyte-stimulating hormone (alpha-MSH) in the hypothalamic arcuate nucleus
      (ARC) were measured with immunohistochemical semiquantitative analysis. RESULTS:
      (1) The food intake and body weight of 2 Hz EA group and 100 Hz EA group were
      decreased significantly compared with the restrain control group and DIO group.
      (2) The number of alpha-MSH positive cells in hypothalamic ARC in 2 Hz EA and 100
      Hz EA group was significantly higher than that in restrain control group and DIO
      group. The number of alpha-MSH positive cells in hypothalamic ARC in DIO group is
      significantly lower than those in DR group or normal control group. CONCLUSION: A
      decrease of alpha-MSH level in hypothalamus may be associated with diet-induced
      obesity. The therapeutic effect on obesity produced by EA may be accounted for by
      the stimulation of pro-opio-melanocortin neurons in hypothalamic ARC to release
      alpha-MSH, which inhibits food intake, resulting in a decrease of body weight.

PMID- 14601299
TI  - [Characteristic of children's EEG complexity at different ages and in different
      states].
AB  - OBJECTIVE: To study characteristics of children's EEG complexity at different
      ages and in different physiological states. METHODS: The continuous 24-hour EEG
      recordings were obtained from 16 electrodes in 45 essential healthy children
      between the ages of 0 to 15 years. EEG complexity was analyzed by non-linear
      measure in 7 states: awake with eyes opened, awake with eyes closed, NREM
      (nonrapid eye movements) sleep including stages I and II (light sleep), III and
      IV (deep sleep) and REM (rapid eye movements) sleep. Meanwhile, the correlation
      was analyzed between complexity and ages. RESULTS: (1) The global EEG complexity
      in state of being awake with eyes opened was greater than that with eyes closed;
      that in wakefulness state was greater than in sleep state. The EEG complexity
      gradually decreased with the increase of deep sleep in NREM sleep state. The
      complexity in REM sleep state was greater than that in deep sleep state, but
      lower than in wakefulness state. (2) The global EEG complexity was positively
      related to ages in state of being awake with eyes opened, state of being awake
      with eyes closed, light sleep, and not related to ages in deep-sleep state and
      REM sleep state. (3) In every brain area EEG complexity was positively related to
      ages in state of being awake with eyes closed. In paracentral region EEG
      complexity was positively related to ages in states of being awake with eyes
      opened and light sleep. CONCLUSION: The EEG complexity was used to study the
      brain dynamical characteristics in different physiology states and the
      relationship between encephalic electric activity and brain development. It can
      be used as an objective index to evaluate the function and development of brain.

PMID- 14601300
TI  - [Effect of intracellular-free Ca2+ concentration on transient magnesium-free
      treatment induced epileptic injury in developing cortical neurons of rats].
AB  - OBJECTIVE: To investigate the effect of intracellular-free Ca2+ concentration
      ([Ca2+]i) on injury following transient Mg(2+)-free treatment in vitro in
      developing cortical neurons. METHODS: Embryo cortical neurons of rats cultured
      for 6 d and 17 d were directly exposed to Mg(2+)-free media, or pretreated with
      NMDA receptor antagonists or calcium channel antagonist before being exposed to
      Mg(2+)-free media. MTT assay was used to study the injury of neurons. [Ca2+]i
      were measured using fluo-3, a fluorescent calcium-sensitive dye and laser
      scanning confocal microscope, and calculated by the fluorescent intensity.
      RESULTS: Compared with control, MTT conversion rates decreased after transient (3
      h) Mg(2+)-free treatment in neurons cultured for 6 d and 17 d in vitro, (59.1 +/-
      6.87)% and (51.2 +/- 5.90)%, respectively. In neurons pre- and co-treated with 10
      mumol.L-1 MK-801, 50 mumol.L-1 AP-5 and 10 mumol.L-1 nifedipine, MTT conversion
      rates were higher than those of neurons with only Mg(2+)-free treatment. Peak
      values of [Ca2+]i in neurons cultured for 6 d and 17 d were 2.4 +/- 0.23 and 3.2
      +/- 0.32, respectively. Peak value of neurons 17 d in vitro was significantly
      higher than that of neurons 6 d in vitro (P < 0.05). In neurons pre- and co
      treated with MK-801, AP-5 and nifedipine, [Ca2+]i were lower than those of
      neurons with only Mg(2+)-free treatment. CONCLUSION: Neuronal injury and [Ca2+]i
      changes following Mg(2+)-free-treatment-induced seizure were different between
      neurons 6 d and 17 d in vitro. It suggested that the age-dependent [Ca2+]i
      changes might play a role in an age-dependent manner of injury following Mg(2+)
      free-treatment-induced seizure. NMDA receptor-Ca2+ pathway activation was crucial
      in the [Ca2+]i change and the cellular injury induced by Mg(2+)-free treatment.

PMID- 14601301
TI  - [Correlation of NDRG1 gene with liver tissue differentiation and
      hepatocarcinogenesis].
AB  - OBJECTIVE: To detect the expression profile of NDRG1 gene in different tissues
      and cell lines and explore the relationship of NDRG1 with liver tissue
      differentiation and hepatocarcinogenesis. METHODS: The expression profiles of
      NDRG1 in hepatocellular carcinoma (HCC) tissues, paired noncancerous liver (PNL)
      tissues, adult normal liver (NL) tissues, baby mouse liver tissues and fetal
      liver tissues in different developmental stages and cultured cell lines were
      performed using RT-PCR and Northern Blot analysis. RESULTS: Expression of NDRG1
      was significantly up-regulated in HCC tissues compared to that of NL tissues and
      PNL tissues, however, the expressions of NDRG1 in NL and PNL tissues showed no
      evident difference. In ten cell lines, the highest expression was in the 293T
      human kidney cell line, the next one in liver cell L02, and the lowest one in the
      undifferentiated HLE cell line. Expression of NDRG1 in liver tissues enhanced
      with the development of the baby mouse and human fetus. CONCLUSION: NDRG1 is
      probably related to the liver cell differentiation and is highly expressed in the
      specific stage of the differentiation. However, it could not be recognized as a
      marker of differentiation. The high expression of NDRG1 in HCC indicates that HCC
      is not just distributed to a simple de-differentiation. Much more study is
      necessary in understanding the comprehensive relationship of the disorder
      proliferation and differentiation of HCC and the related genes.

PMID- 14601302
TI  - [Transplantation of bone marrow cells up-regulated the expressions of HSP32 and
      HSP70 in the acute ischemic myocardium].
AB  - OBJECTIVE: To clarify the role of Heat shock proteins (HSPs) on the cardiac
      function during acute myocardial infarction (AMI) after bone marrow cell
      implantation (BMT), we examined the expression of HSP32 and HSP70 in a rat model
      of myocardial infarction. METHODS: Myocardial infarction model was induced in the
      inbred Lewis rats by left anterior descending artery ligation, and 5 x 10(6) of
      bone marrow-mononuclear cells (BM-MNCs) were injected into an ischemic zone. On
      days 1, 3, 7 and 14 post-infarct, the differentiations of transplanted cells and
      the expressions of HSP32 and HSP70 were determined by immunofluorescence or RT
      PCR. The cardiac function was evaluated by echocardiography. RESULTS:
      Immunofluorescence microscopy of hearts from BMT group revealed that expressions
      of HSP32 and HSP70 were promoted within cardiomyocytes in the infarction zone and
      the peri-infarct zone, and expressed within some transplanted bone marrow cells
      as well. RT-PCR also showed the mRNA expression levels of HSP32 and HSP70 in BMT
      group were significantly higher than those of the control group, peaked on day 3
      post-infarct (5.0-fold and 2.9-fold, respectively, P < 0.01), and then gradually
      reduced. On day 7 post-infarct, cardiac function (EF and FS) was improved, more
      than that of the control group (14% and 22%, P < 0.05). On day 14 post-infarct,
      the specific markers for myocardium or vascular endothelial cells were detected
      in the transplanted bone marrow cells. The cardiac function was further improved
      in the BMT group (P < 0.01). CONCLUSION: At the early phase after BMT, the
      expressions of HSP32 and HSP70 were upregulated in both transplanted cells and
      recipient endogenous cardiomyocytes, which improved the acute ischemic cardiac
      function.

PMID- 14601303
TI  - [Characterization of programmed cell death 5 (PDCD5) gene in human cartilage and
      its possible significance].
AB  - OBJECTIVE: To characterize the expression of programmed cell death 5 (PDCD5) in
      normal and osteoarthritic human cartilage. METHODS: Articular cartilage specimens
      were obtained from 20 patients with osteoarthritis and 10 with femoral neck
      (normal cartilage) at the time of arthroplasty. Expression of PDCD5 was detected
      by flow cytometry, immunofluorescence, RT-PCR and immunohistochemical analysis.
      RESULTS: PDCD5 expression in osteoarthritis cartilage was significantly higher
      than in normal cartilage especially in the nucleus. PDCD5-positive chondrocytes
      were mainly observed in the superficial and deep zone of osteoarthritis tissue
      sections, and in contrast, in the superficial and middle regions of normal
      controls. CONCLUSION: Since apoptotic chondrocyte death occurs more frequently in
      osteoarthritis compared to normal cartilage and PDCD5 is an apoptosis related
      protein, the different expression patterns of PDCD5 in osteoarthritis and normal
      cartilage suggest that it might be involved in the pathogenesis of
      osteoarthritis.

PMID- 14601304
TI  - Detection of Treponema pallidum DNA in cutaneous lesions of secondary syphilis
      and characterization of the inflammatory infiltrate.
AB  - OBJECTIVE: To investigate the possible mechanism of the cutaneous lesion
      formation in secondary syphilis and role of cellular immunity in the pathogenesis
      of syphilis. METHODS: Treponema pallidum DNA was detected in 24 formalin-fixed,
      paraffin-embedded skin specimens from lesions of secondary syphilis by nested
      PCR. The inflammatory infiltrate in the cutaneous lesions of secondary syphilis
      was investigated using immunohistochemical technique. RESULTS: The TP-specific
      DNA was found in 10 of 24 (45.8%) lesions of secondary syphilis. However, no
      Treponema pallidum were found in all 24 tissue section samples when silver
      staining was performed. CD45RO (+) Tcells were found in all syphilis lesions with
      strong staining. CD68 (+) cells were found in 68.2% of the skin specimens.
      Meanwhile, a few CD20 (+) cells and CD57 (+) cells were seen in the infiltrates.
      CONCLUSION: The cutaneous lesions might be formed by invasion of TP to skin
      rather than an allergic reaction. The predominant T cells and macrophages
      infiltrating in secondary syphilitic lesions indicate that cellular immunity
      might play a critical role in host reaction against TP infection.

PMID- 14601305
TI  - [The regulatory effect of endogenous hydrogen sulfide on hypoxic pulmonary
      hypertension].
AB  - OBJECTIVE: To study the changes of endogenous H2S and the effect of exogenously
      applied H2S on hypoxic pulmonary hypertension (HPH). METHODS: Male Wistar rats
      were randomly divided into control group (n = 6), hypoxia group (n = 7) and
      hypoxia + NaHS group (n = 6). The rats that received hypoxia were put into a
      normobaric hypoxic chamber to respire hypoxic gas containing 10% (volume
      fraction) O2 for 6 hours everyday. NaHS solution was injected to rats of hypoxia
      + NaHS group at a dosage of 0.78 mg.kg-1 before hypoxic challenge. After 21 days
      of hypoxia, the mean pulmonary artery pressure (mPAP) was measured. The weight
      ratio of right ventricle vs left ventricle and septum [RV/(LV + SP)] was
      measured. The microstructure and ultrastructure changes in pulmonary small
      arteries were examined using elastin staining and transparent electron microscope
      respectively. And the activity of H2S generating enzymes in homogenates of the
      lung tissue and pulmonary artery was measured. The cystathionine gamma--lyase
      (CSE) mRNA in lung tissue was also measured using quantitative RT-PCR. RESULTS:
      Compared with rats in the control group, the mPAP increased 45.6% (P < 0.01) and
      the RV/(LV + SP) ratio increased 41% (P < 0.01) in rats of hypoxia group
      respectively. The relative medium thickness (RMT) and relative medium areas (RMA)
      increased 41% and 49% respectively (P all < 0.01) under optical microscope. The
      ultrastructure of the pulmonary small arteries also changed significantly. The
      H2S generating enzyme activity in lung tissue and in pulmonary artery decreased
      52% and 54% respectively (P < 0.01). There were obviously negative correlations
      between the mPAP and H2S generating enzymes ativity. Relative CSE mRNA amount in
      lung tissue also decreased 53% (P < 0.01) in rats of hypoxia group compared with
      that of control group. The mPAP, and the RV/(LV + SP) ratio of rats in hypoxia +
      NaHS group decreased 31.2%, and 24% respectively compard with that of hypoxia
      group (P < 0.01). The RMT and RMA in rats of hypoxia + NaHS group also decreased
      36% and 31% respectively (P < 0.01). In hypoxia + NaHS group, the H2S generating
      enzymes activity and relative CSE mRNA amount in the lung tissue increased 67.7%
      and 110% respectively compared with those in hypoxia group (P all < 0.01).
      CONCLUSION: Endogenous H2S was involved in the pathogenesis of rat's HPH.
      Exogenously applied H2s could exert protective effect during HPH.

PMID- 14601306
TI  - Purification of alpha chain NC1 domains of type IV collagen from bovine kidney
      and their application in ELISA for detecting anti-glomerular basement membrane
      antibodies.
AB  - OBJECTIVE: To purify alpha chain NC1 domains of type IV collagen [alpha (IV) NC1]
      from bovine kidney and to evaluate their application in ELISA for detecting anti
      glomerular basement membrane (GBM) antibodies. METHODS: Glomeruli were isolated
      by differential sieving from bovine kidney, and GBM was isolated by 40 g.L-1
      deoxycholic acid extraction technique. Then the insoluble basement membrane
      material was digested using collagenase, and the non-collagenous domain (NC1) was
      isolated by Mono Q ion exchange chromatography. The purity and activity of the
      purified alpha (IV) NC1 technique were assessed using SDS-PAGE and Western blot
      analysis. An ELISA was established using purified bovine alpha (IV) NC1 as solid
      phase antigens to detect anti-GBM antibodies. Ninety sera from patients with
      known anti-GBM antibody positive were tested by alpha (IV) NC1-ELISA. One hundred
      sera from healthy blood donors and fifty sera from patients with other renal
      diseases were used as controls. The specificity and the sensitivity of the method
      were evaluated. RESULTS: Bovine alpha (IV) NC1 was purified with 25 x 10(3) and
      50 x 10(3) on SDS-PAGE and could be blotted by known anti-GBM antibody positive
      sera. The specificity and the sensitivity of the alpha (IV) NC1-ELISA were 98%
      and 100% respectively. CONCLUSION: Purified bovine alpha (IV) NC1 could be used
      as a substitute for human alpha (IV) NC1 to detect anti-GBM antibodies.

PMID- 14601307
TI  - [PPAR-gamma expression in the kidney of actively proliferating
      glomerulonephritis].
AB  - OBJECTIVE: To investigate peroxisome proliferator-activated receptor gamma (PPAR
      gamma) expressions in patients with actively proliferating glomerulonephritis
      such as type IV lupus nephritis (LN) and cellular crescentic glomerulonephritis
      (RPGN). METHODS: All patients were divided into 4 groups as follows: RPGN (17
      cases); LN type IV (15 cases); mild mesangial proliferative IgA nephropathy
      (IgAN, 7 cases) and minimal change disease (MCD, 10 cases). Clinical parameters,
      immunohisto-chemistry stain and in situ hybridization of renal biopsy specimens
      were performed. RESULTS: Clinically, proteinuria and hematouria were increased
      and Ccr were decreased in LN and RPGN patients, and increased ESR and decreased
      complement C3 were found in group LN. Active index of renal specimens were
      significantly higher in LN and RPGN groups than in IgAN and MCD groups. Renal
      specimens of MCD patients showed no positive PPAR-gamma staining in all sections;
      little immunoreactivity was detected in sections of glomerular, tubular and
      interstitial cells from IgAN patients. Glomerular positive staining of PPAR-gamma
      in renal sections in LN and RPGN patients[(3.3 +/- 1.8) and (2.8 +/- 1.2) cells
      per section of glomerulus, respectively] were significantly increased compared
      with that in IgAN patients [(0.7 +/- 0.5) cells per section of glomerulus].
      Similarly, tubular positive staining of PPAR-gamma in LN and RPGN patients (27.38
      +/- 12.46, 23.36 +/- 10.55) were also elevated compared with that in IgAN and MCD
      patients(6.51 +/- 3.49, 1.72 +/- 0.31). The relevance assay results showed
      positive relationship between active index and glomerular or tubular PPAR-gamma
      immunohisto-chemistry staining cell numbers (0.478, P < 0.01; 0.513, P < 0.01).
      Tubular PPAR-gamma mRNA expression in LN and RPGN patients was upregulated by in
      situ hybridization. CONCLUSION: Our results demonstrate in vivo that PPAR-gamma
      expression was increased in active glomerulonephritis patients accompanied with
      clinical and pathological active inflammation. These data suggest that increase
      of PPAR-gamma expression in renal cells may play an important role in response to
      inflammatory stress.

PMID- 14601308
TI  - [Relationship between tubulointerstitial fibrosis and mononuclear-macrophage].
AB  - OBJECTIVE: To study the relationship between monocyte/macrophage (MC/MP)
      accumulation and tubulointerstitial fibrosis. METHODS: The renal
      tubulointerstitial fibrosis model in Wistar rats was established by unilateral
      renal vein ligature. The rats were fed for 25 days. The kidneys were obtained
      every 5 days by killing the rats. The morphological changes of tubulointerstitial
      fibrosis were observed by light microscopy with HE, PAS, PASM and Masson
      staining. Immunohistochemistry and double immunohistochemistry were used to
      observe MC/MP accumulation and proliferation. In situ hybridization and
      immunochemistry were used to observe MCP-1 and M-CSF expression in experimental
      renal tissue. The MCP-1 protein expression was inspected by Western blot. All the
      data were analyzed statistically. RESULTS: The pathological changes of
      tubulointerstitial fibrosis were typical. There were many MC/MPs accumulsated in
      the interstitial space at the early stage and some of them were PCNA positive. At
      the late stage both accumulation and proliferation of MC/MPs were decreased. The
      portion of monocyte proliferation was high correlated with the MC/MP
      accumulation. In situ hybridization showed the positive signals of MCP-1 and M
      CSF were mainly located in the cytoplasm of degenerated tubular epithelium and
      they were strong at the early stage, weak at the late stage. MCP-1 by
      immunochemistry and Western blot were consistent with in situ hybridization. The
      MC/MP accumulation was high correlated with the expression of MCP-1 and tubular
      epithelium degeneration. The portion of monocyte proliferation was high
      correlated with the expression of M-CSF. CONCLUSION: There was obvious
      accumulation of MC/MP at the early stage of tubulointerstitial fibrosis. The
      accumulation came from infiltration and proliferation which were regulated by
      degenerated tubular epithelial cells producing MCP-1 and M-CSF. MC/MP
      accumulation was highly correlated with tubular degeneration. MC/MP promoted
      tubulointerstitial fibrosis and damaged tubular epithelium by secreting a variety
      of cytokines.

PMID- 14601309
TI  - [Involvement of endothelin in the proliferative effect of lysophosphatidic acid
      on vascular smooth muscle cells in rats].
AB  - OBJECTIVE: To observe the effects of lysophosphatidic acid (LPA) on production of
      endothelin (ET) in rat aorta vascular smooth muscle cells (VSMCs). METHODS:
      Cultured VSMCs were used in the study. DNA synthesis of VSMCs was measured by 3H
      TdR incorporation. The amount of ET mRNA of VSMCs was determined by competitive
      quantitative RT-PCR. The levels of synthesis and release of ET in VSMCs were
      determined by radioimmunoassay (RIA). RESULTS: 5-20 mumol.L-1 of LPA promoted
      VSMCs 3H-TdR incorporation in a concentration dependent manner. The amount of ET
      mRNA in VSMCs treated by 5-20 mumol.L-1 of LPA was increased by 16%, 21%, and
      23%, respectively, compared with the control. After 8 hours of incubation, 5-20
      mumol.L-1 of LPA elevated the ET production in a concentration dependent manner.
      After 8 hours of VSMCs incubated with LPA (5-20 mumol.L-1), the content of ET in
      medium was increased by 140%-200%, respectively, compared with the control. In
      addition, it was found that BQ123, a non-selective ET receptor antagonist,
      greatly decreased the VSMCs DNA synthesis induced by LPA. CONCLUSION: LPA
      stimulated the ET mRNA expression and ET production in VSMCs. The effects of LPA
      on VSMCs DNA synthesis were partly mediated by ET/ETA receptor pathway. It
      suggests that LPA and ET interact and exert biological effects as endogenous
      active peptides.

PMID- 14601310
TI  - [Coronary artery bypass grafting after acute myocardial infarction].
AB  - OBJECTIVE: To analyze 88 cases of coronary artery bypass grafting (CABG) within
      30 days after acute myocardial infarction(AMI). METHODS: 88 cases included 18
      cases with emergent angioplasty, 26 cases with postinfarctional angina pectoris,
      9 cases with cardiogenic shock and 25 cases with left main lesion. RESULTS: There
      were 75 cases underwent off pump coronary artery bypass(OPCAB) and 13 cases
      underwent beating heart CABG with cardiopulmonary bypass(BH-CPB). The mean number
      of bypass grafts was 3.4 +/- 0.9. Five patients with preoperative cardiogenic
      shock died after emergent operations. There were 4 cases with postoperative heart
      failure, 6 cases with PSVT and 2 cases with bradycardial and treated pacemaking.
      CONCLUSION: It was neccessry and feasible to perform CABG within 30 days after
      AMI. Both the OPCAB and BH-CPB were safe methods.

PMID- 14601311
TI  - Surgical experience of 179 cases with craniopharyngiomas.
AB  - OBJECTIVE: To retrospectively review 179 cases surgical treatments of
      craniopharyngiomas over a 7-year period, surgical experience as following.
      METHODS: Dependent on the locations of the tumors to the floor of the third
      ventricle, they were classified into the superior type of the third ventricle
      floor in which tumors grew on the superior part of the third ventricle floor, and
      the inferior type of the third ventricle floor in which tumors grew from the
      pituitary stalk, infundibulum, tuber cinereum upwards the floor of the third
      ventricle developing the obstruction of the third ventricle or downward to the
      intral sella through the foramen of sellar septum. As the tumor of the inferior
      type, the pterional approaches were performed in 150 patients and the subfrontal
      approach in 16 patients. As the superior type, transcallosum into the anterior
      third ventricle part were undergone in 13 cases. Great care was made to preservie
      the perforating arteries to the neural structures of the third ventricular floor
      for the tumor of the inferior type. Avoidance of injury was required to the
      neural structures of the third ventricular floor when used by the transcallosum
      approach to the anterior part of the third ventricular floor for the tumor of the
      superior floor. RESULTS: Total, subtotal and partial removal of the tumor was
      achieved in 161, 12 and 6 patients, respectively. Four (2.2%) deaths occurred at
      early postoperative stage. All patients were followed-up from 3 months to 5 years
      (mean, 1.5 years), with 154 (88%) patients regained normal life, 14 (8%) had
      their self-life and the 7 (4%) need assist life. Seven (3.9%) patients
      experienced their tumor recurrence on MR imaging by following-up. Of them, 4
      patients were followed up their tumor recurrence within half-year and 3 patients
      within one year. Five patients with recurrent tumor were reoperated on and the
      other 2 patients were undergone the external radiation of the tumor and gamma
      knife of the tumor respectively. CONCLUSION: Craniopharyngiomas can be treated
      surgically with a good result. It is the key to avoid injury of the hypothalamic
      structures and preserve the perforating arteries to hypothalamus to achieve good
      surgical results, while attempt was made to completely remove the tumor.

PMID- 14601312
TI  - [Alteration of the expression of cartilage matrix molecule in the cartilage by
      the chondrocytes from rabbit temporomandibular joint with experimental
      osteoarthritis and its response to interleukin-1 beta].
AB  - OBJECTIVE: To study the effect of interleukin-1 (IL-1 beta) on the metabolism of
      osteoarthritic and normal mature condylar chondrocytes in temporomandibular
      joints, and investigate the role of IL-1 beta in the pathogenesis of
      temporomandibular joint osteoarthritis. METHODS: The primary generation of
      osteoarthritic and normal condylar chondrocytes cultured in the monolayer
      condition was treated with 20 micrograms.L-1 recombined human interleukin-1 beta
      (rhIL-1 beta), and then collected to be detected with RT-PCR method for the
      cellular metabolism including mRNA expression of type II collagen, aggrecan,
      collagenase, insulin-like growth factor 1 (IGF-1), and transforming growth factor
      beta 1 (TGF beta 1). RESULTS: The normal mature condylar chondrocytes showed the
      obviously decreased mRNA expression of type II collagen and aggrecan after the
      intervention of exogenous IL-1 beta, but less influence could be found for the
      collagenase expression. The osteoarthritic condylar chondrocytes exhibited the
      decreased mRNA expression of type II collagen and collagenase under the effect of
      IL-1 beta, while the cellular mRNA expression of aggrecan didn't change
      obviously. The intervention of exogenous IL-1 beta didn't show an obvious
      influence on the cellular expression of endogenous growth factors such as IGF-1
      or TGF-beta 1 for both the normal and osteoarthritic condylar chondrocytes
      cultured in vitro. CONCLUSION: IL-1 beta could not only disturb the expression of
      cartilage matrix molecules by the normal condylar chondrocytes, which lead to the
      lesion of condylar cartilage, but also worsen the abnormal cartilage matrix
      environment within the osteoarthritic condylar cartilage.

PMID- 14601313
TI  - [Three-dimensional measurement of tooth inclination in cases with successful
      treatment].
AB  - OBJECTIVE: This study aimed to observe the differences of tooth inclinations
      among post-treatment good cases of different malocclusions and untreated normal
      occlusions in order to give references on clinical adjusting of tooth
      inclinations. METHODS: 157 post-treatment good cases were chosen and tooth
      inclinations were measured on post-treatment casts using YM-2115 three
      dimensional measurement instrument. The measurement results were compared with
      those of untreated normal occlusions. RESULTS: The inclination values of upper
      and lower incisors of Class I groups are most close to those of untreated normal
      occlusions, which of upper central and lateral incisors are 9.6 degrees and 8.7
      degrees, and of lower central and lateral incisors are 1.1 degrees and -1.1
      degrees. In Class II groups, lower incisors are markedly proclined (5.6 degrees
      and 2.1 degrees) and upper incisors are similar with untreated normal occlusions.
      In Class III groups, upper incisors are markedly proclined (15.2 degrees and 12.1
      degrees) and lower incisors are markedly retroclined (-3.7 degrees and -4.9
      degrees). CONCLUSION: In order to achieve normal overjet and overbite, it is
      necessary to adjust the inclinations of upper and lower incisors when treated
      Class II and Class III malocclusions only by the method of orthodontic treatment.

PMID- 14601314
TI  - [Effect of trigeminus nerves innervation on the phenotype of MHC after facial
      paralysis].
AB  - OBJECTIVE: To discuss the effect of trigeminus nerves on the phenotype of MHC
      after facial paralysis; METHODS: The morphologic changes were observed by
      histochemical methods, the phenotype of MHC by SDS-PAGE, the tension of
      contraction and the threshold value of electrical stimulation by electrical
      physiological methods; RESULTS: Trigeminus nerves could delay the decomposing of
      MHC, maintain the tension of contraction and the threshold value of electrical
      stimulation; CONCLUSION: Sensory nerves could delay the muscular atrophy, and
      should be repaired when we repair motor nerves.

PMID- 14601315
TI  - [Simvastatin induces osteoblastic differentiation of bone marrow stromal cells].
AB  - OBJECTIVE: To observe the effect of simvastatin on osteoblastic cell
      differentiation of bone marrow stromal cells in vitro, and to elucidate the
      mechanisms of anabolic effect of simvastatin on bone formation. METHODS: Bone
      marrow stromal cells from femur and tibia of adult female BALB-C mice were
      cultured in vitro, after being treated with different concentrations of
      simvastatin for 72 h, changes of mRNA level of osteocalcin (OCN) were detected by
      RT-PCR, change of OCN, and osteopontin (OPN) expression were examined by Western
      blot, and the changes of cellular alkaline phosphatase activity (ALP) were
      examined by histochemistry and enzymologic measurement. RESULTS: After bone
      marrow stromal cells were treated with different concentration of simvastatin for
      72 h, level of OCN mRNA increased, and expression of OCN and OPN also increased
      in a concentration-dependent manner, and cellular ALP activity significantly
      increased in a concentration-dependent manner. CONCLUSION: Simvastatin can
      stimulate osteoblastic differentiation, and improve cellular ALPase activity with
      high expression of osteocalcin and osteopontin in vitro. These may be parts of
      the mechanism of anabolic effect of simvastatin on bone formation.

PMID- 14601316
TI  - [Pioglitazone, a peroxisome proliferators-activated receptor gamma ligand,
      inhibits dimethylhydrazine (DMH) induced aberrant crypt foci in rats].
AB  - OBJECTIVE: To investigate the chemopreventive effects of pioglitazone (exogenous
      PPAR gamma ligand) on rat colon aberrant crypt foci, a rat carcinogenesis model
      induced by dimethylhydrazine (DMH), and to compare pioglitazone with sulindac (a
      NSAID). METHODS: Thirty-two, 8-week-old, female Sprague-Dawley rats were randomly
      divided into four groups (n = 8 each). Group 1 rats were injected with DMH alone
      (120 mg.kg-1, single subcutaneous injection). Group 2 rats were injected with
      saline alone. Group 3 rats were pre-treated with sulindac (320 mg.kg-1) for 7
      days before DMH initiation. Group 4 rats were treated with pioglitazone (100
      mg.kg-1). The animals were killed at the end of the experiment (week 5) and the
      colons were stained with methylene blue. The aberrant crypt foci (ACF) of the
      colonic mucosa were assessed. RESULTS: In Group 1 rats (DMH only), the average
      numbers of ACF/colon and AC/colon were (182 +/- 93) and (263 +/- 198),
      respectively. In Group 2 (saline group) rats, no ACF were found. In Group 3
      (sulindac group) rats, the average numbers of ACF/colon and AC/colon were (91 +/-
      49) and (140 +/- 69), respectively. Both of them were decreased significantly
      compared with the values in Group 1 (P < 0.01 and P < 0.05). In Group 4
      (pioglitazone group) rats, the average numbers of ACF/colon and AC/colon were (97
      +/- 23) and (148 +/- 31), respectively. Both of them were decreased significantly
      compared with the values in Group 1 (P < 0.01 and P < 0.05). No difference was
      found in the values of Group 3 and Group 4. CONCLUSION: These results suggest
      that pioglitazone have chemopreventive effects against rat colon carcinogenesis
      induced by DMH, whose effect is similar to that of sulindac.

PMID- 14601317
TI  - [Study of autofluorescence spectrum of dilute gastric juice in the diagnosis of
      gastric carcinoma].
AB  - OBJECTIVE: To investigate the value of the autofluorescence spectrum of dilute
      gastric juice in the diagnosis of gastric carcinoma. METHODS: The
      autofluorescence spectrum of dilute gastric juice was scanned with RF-5000
      spectrophotofluorometer when the excitation wavelength was set to 288 nm and the
      emission wavelength ranged from 300 nm to 800 nm. RESULTS: We enrolled 251
      patients with different gastric diseases including 40 cases with gastric
      carcinoma in our study. There were three characteristic peaks in the
      autofluorescence spectrum of gastric juice, which appeared in the spectra of both
      dilute and indilute specimens, but relative fluorescence intensity index (FI) of
      the peaks changed with concentration. The spectra of dilute gastric juice (1:20)
      of both benign and malignant gastric diseases had those three peaks. However, the
      fluorescence intensity index of the first peak (P1FI) at 320-360 nm of patients
      with gastric carcinoma was higher than that of patients with benign gastric
      diseases. The diagnosis model for gastric carcinoma was made by CART V2.0
      software. The diagnosis standard for gastric carcinoma was P1FI > 38.995. The
      model's sensitivity and specificity of prior probability were 85.0% and 91.9%
      respectively. The sensitivity and specificity of posterior probability were 82.5%
      and 91.9% respectively. When the diagnosis standard was set to P1FI > 24.34, the
      sensitivity and specificity were 95.0% and 75.8%, respectively. CONCLUSION: The
      autofluorescence spectrum of dilute gastric juice may become an effective means
      in the diagnosis and screening of gastric carcinoma.

PMID- 14601318
TI  - [Influence of inhaled nitric oxide on surfactant in the total cardiopulmonary
      bypass pig model].
AB  - OBJECTIVE: To study whether or not inhaled nitric oxide (INO) can improve
      surfactant production and pulmonary mechanics after CPB in pigs, and to seek the
      mechanism of lung injury during mechanical ventilation. METHODS: Thirty pigs were
      randomized into 6 groups: Sham (n = 5), Sham + INO (n = 5), CPB (n = 5), CPB +
      INO (n = 5), CPB + lipopolysaccharide (LPS) (n = 5), and CPB + LPS + INO (n = 5).
      After anesthesia induction, INO (mass fraction, 20 x 10(-6)), added to the gas
      mixture, was given to the animals throughout the procedure. After 2 hours of INO
      treatment, broncho-alveolar lavage (BAL) fluid was taken for surfactant assay and
      cytology analysis. Pulmonary hemodynamics parameters and lung compliance were
      measured as well. CPB was performed for 90 minutes after the first BAL sampling
      at T0. Four hours (T4) and 24 hours (T24) following CPB, BAL and other
      measurements were repeated. After CPB, LPS (4 micrograms.kg-1) was infused to
      specific groups of pigs within 90 minutes in order to stimulate the inflammation
      process. RESULTS: Pulmonary hemodynamics parameters (pulmonary artery pressure,
      pulmonary vascular resistance and oxygenation) in all INO groups were much better
      than those of the control groups at T4 and T24. However, lung compliance of pigs
      in all groups declined with time, and showed statistically significant
      differences at T24 compared with T0. At T0, the active subfraction of surfactant
      (large aggregate, LA) was increased in animals given INO treatment compared with
      the controls, but decreased with time, and at T24 significantly reduced in all
      groups. In LPS groups, this decrease LA after T4 was very obvious. Total cell
      counts and the percent differentials of neutrophils in BAL increased with time,
      being lower in the INO groups than in other groups. CONCLUSION: INO exposure
      exerted time-related effects on the lung surfactant (LA). Initially, INO resulted
      in short-term increase of surfactant production at T0. However, with time passing
      by, INO exposure following CPB did not prevent long-term decrease of lung
      surfactant and lung compliance although INO was beneficial for pulmonary
      hemodynamics and oxygenation. In summary, despite the use of INO, synergetic
      effects of long-term hyperoxia, mechanical ventilation and inflammation following
      CPB may exacerbate pulmonary mechanics and result in surfactant dysfunction.

PMID- 14601320
TI  - [Clinical features and management of recurrence of severe acute respiratory
      syndrome].
AB  - OBJECTIVE: To investigate the clinical features of recurrence of severe acute
      respiratory syndrome (SARS) and therapeutic response. METHODS: Recurrence was
      analyzed retrospectively in SARS patients referred to our hospital from April to
      May this year to understand the clinical features, the recurrent related factors,
      the response of treatment and the outcomes. RESULTS: One hundred and twenty three
      patients with SARS were referred to the First Hospital of Peking University from
      8, April to 14, May this year and of whom 51 were the critical. Twenty-five
      patients experienced recurrence, account for 20.3% of total patients (25/123) and
      31.4% of critical patients. The clinical features included recurrent fever,
      worsened breathlessness, exacerbation in radiological lesions and elevated LDH,
      etc.. These patients were treated with glucocorticoids. Eleven of them were
      mechanical ventilated. Twenty-one patients recovered. Pulmonary fibrosis were
      left in 2 patients and another 2 patients died. CONCLUSION: The recurrence of
      symptoms in SARS patients is one of the common clinical feature of critical
      patients with SARS. Mechanism of recurrence in SARS patient is unknown.
      Management with glucocorticoids and noninvasive ventilation can control the
      progression in these patients effectively.

PMID- 14601319
TI  - [Target-controlled infusions of remifentanil and propofol during laparoscopic
      cholecystectomy].
AB  - OBJECTIVE: To evaluate the clinical profile of target-controlled infusion-based
      anesthesia using remifentanil and propofol. METHODS: 16 ASA I-II patients
      undergoing elective laparoscopic cholecystectomy were enrolled. Remifentanil was
      set at 7 micrograms.L-1 as target and profol at 3 mg.L-1 throughout the whole
      procedure. The hemodynamics during induction of anesthesia and recovery profiles
      were recorded. Arterial blood samples for analysis of remifentanil were taken 15
      min after infusion, 20 min after infusion and at time of emergence. RESULTS:
      After induction of anesthesia, systolic blood pressure (SBP) decreased from (144
      +/- 27) mm Hg to (101 +/- 18) mm Hg (P < 0.05), mean blood pressure (MBP)
      decreased from (102 +/- 15) mm Hg to (69 +/- 13) mm Hg (P < 0.05) and heart rate
      (HR) decreased from (77 +/- 14) beats.min-1 to (63 +/- 12) beats.min-1 (P >
      0.05). SBP, MBP and HR remained stable after intubation for 3 min. No patient
      showed haemodynamic stress to tracheal intubation. Times from stopping
      administration of anesthetics until full spontaneous respiration, eye opening,
      tracheal extubation, orientation and discharging from the postanesthetic care
      unit (PACU) were (12 +/- 6), (9 +/- 4), (13 +/- 6), (15 +/- 5) and (19 +/- 7) min
      respectively. Measured drug values of remifentanil were (4.6 +/- 9.5) microgram.L
      1, (6.6 +/- 11.5) microgram.L-1, (1.2 +/- 8.7) microgram.L-1 respectively.
      CONCLUSION: Remifentanil/propofol TCI-based anesthesia achieved the optimal
      hemodynamic stability during anesthesia induction and maintenance, and better
      recovery profile from anesthesia. Measured drug values of remifentanil showed a
      considerable interindividual variation and more lower than the set target.

PMID- 14601321
TI  - [Cardiac presentations in patients with SARS].
AB  - OBJECTIVE: To investigate the impact of SARS on heart initially. METHODS: The
      clinical and laboratory data of 86 patients with SARS were collected and analyzed
      statistically. RESULTS: In recovery phase, the rest heart rates in 64% of
      patients with SARS exceeded 90 bpm, and the heart rates after mild exercises in
      72.1% of patients with SARS exceeded 100 bpm. CONCLUSION: SARS, which mainly
      resulted in pulmonary damage, may involve heart.

PMID- 14601322
TI  - Kidney transplantation--new developments.
AB  - The standard of care for patients with end-stage renal disease is kidney
      transplantation, which not only confers a survival benefit compared to
      hemodialysis, but is also cost-effective. The indications, contraindications as
      well as the preoperative assessment of recipients are discussed. The recurrence
      rate of the underlying renal disease has to be taken into account, especially in
      living donation. Growing organ shortage has lead transplant surgeons to accept
      older, less healthy, and even non-heart-beating donors, with generally good
      results. Living-donation is safe for the donor, outcome is excellent and plays an
      increasing role today. It has surpassed the number of cadaveric kidney
      transplantations in some countries. Many centres now apply laparoscopic donor
      nephrectomy with low morbidity. Matching for ABO blood group and HLA is routinely
      performed, as well as pre-transplant crossmatching. The surgical procedure has
      been standardized and the complication rate is low. Immunosuppressive protocols
      have evolved over time, and while the optimal regimen has not been defined, the
      availability of numerous agents allows the regimen to be individualized. New
      agents are being introduced into clinical practice. With increasing long-term
      graft survival and thus life-long immunosuppression, cardiovascular disease, de
      novo malignancies and infectious complications are major causes of morbidity and
      mortality of transplant recipients. Effective prophylactic measures are often
      available, and surveillance protocols are warranted in these patients. Overall,
      the outcome of renal transplantation is excellent and has improved over time.
      Future prospects include induction of allograft tolerance, tissue engineering and
      xenotransplantation.

PMID- 14601323
TI  - Dual transplant of marginal kidneys. Case report and review of the literature.
AB  - INTRODUCTION: Double transplantation is one possible answer to the shortage of
      donor organs. While each donor kidney would be unsuitable when considered as a
      single allograft, use of both kidneys should provide sufficient nephron mass for
      effective glomerular filtration. CASE REPORT: This is the first Swiss report of a
      dual adult transplant of marginal kidneys in a 46-year-old man, who was
      transplanted for the fourth time. Follow-up at 6 months is excellent without
      acute rejection. CONCLUSION: Recent analysis of dual marginal versus single ideal
      transplant outcomes, found a comparable 1-yr graft survival in both of the
      procedures. Long term results are still lacking and guidelines to decide between
      single, double or no transplantation are emerging.

PMID- 14601324
TI  - Clinical lung transplantation--current status.
AB  - Since 1983, lung transplantation has enjoyed increasing success and has become
      the mainstay of therapy for most end-stage lung diseases. While the first decade
      of clinical lung transplantation focused on technical details of the transplant
      procedure, the second decade was characterized by improvements in techniques of
      lung preservation and in the postoperative management. This review will focus on
      the recent improvements made in lung preservation and postoperative management.

PMID- 14601326
TI  - Adult-to-adult living-donor liver transplantation. A summary of current status
      and an outline of the program in Geneva.
AB  - Living donor liver transplantation is a relatively new procedure in which the
      right side of the liver is harvested in a healthy donor and transplanted into a
      recipient. After the first case in 1994, over 3000 cases have been done
      worldwide. This review summarizes the reasons why the procedure is needed,
      describes its main technical aspects, highlights the boundaries in which it can
      be done safely, summarizes the current experience worldwide and describes the
      main points of the program in our unit. We argue that living-donor
      transplantation is a viable alternative to a long time on the waiting list for
      several patients, and it can be performed safely and successfully provided that
      all precautions are undertaken to minimize the risks in the donor and to increase
      the chances of a good outcome in the recipients. If these prerequisites are met,
      and within the framework of a structured multidisciplinary program, we believe
      that living-donor liver transplantation should be funded by health insurances as
      a recognized therapeutic option.

PMID- 14601325
TI  - [The heart transplant in Lausanne from 1987 to 2003].
AB  - Since the availability of ciclosporine, the survival after heart transplantation
      has dramatically improved. We present our results since the beginning of our
      experience in 1987. We treated in the Lausanne University hospital, 150 patients
      for end-stage cardiac disease. Hundred and fifty-two transplantations were
      performed. The survival rate is comparable to the literature with 81% at one
      year, 70% at five year and 63 at ten year included the hospital mortality. We
      review the incidence of complications during the follow-up and report the
      modification in the management of these patients especially concerning the
      immunosuppression.

PMID- 14601327
TI  - Medical problems occurring during the long-term follow-up after liver
      transplantation.
AB  - Liver transplantation is a standardized therapy for end-stage liver disease. With
      current immunosuppressive protocols and patient care, ten-year patient survival
      rate has reached 60%. Several medical complications may develop during this
      period, including renal dysfunction, hypertension, diabetes mellitus,
      hyperlipidemia, and metabolic bone disease. The aim of this article is to analyze
      long-term results of several clinical trials reporting common medical
      dysfunctions after liver transplantation and to discuss their management.

PMID- 14601328
TI  - Islet of Langerhans transplantation for the treatment of type 1 diabetes.
AB  - Islet of Langerhans transplantation is gaining recognition as a therapy for type
      1 diabetes. The procedure involves enzymatic digestion of the pancreatic tissue,
      purification of the islets from the exocrine tissue, infusion of the islets into
      the portal vein and implantation in the liver. Until 1999, and overall rate of
      insulin independence of 14% at one year was reported in the International Islet
      Transplant Registry. The results of the "Edmonton protocol" since 2000 were a
      breakthrough in the field, with reports of 80% insulin independence at 1-year
      after solitary islet transplantation in non uremic patients with brittle type 1
      diabetes. A rapamycin-based, steroid-free, islet-sparing immunosuppressive
      regimen was designed and the problem of the insufficient islet mass was tackled
      by sequential infusions of islets isolated from at least two pancreatic. The
      University of Geneva has been involved in clinical islet transplantation since
      1992, and has performed 51 allogeneic and 17 autologous. Twenty-one patients have
      been transplanted in Geneva since 2002. They were five solitary islet
      transplants, 14 islet after kidney transplants and two simultaneous islet-kidney
      (SIK) recipients. Insulin independence was achieved in 67%.

PMID- 14601329
TI  - [The Sorin pericardial bioprosthesis--a stentless aortic valve with very good
      hemodynamic performance].
AB  - BACKGROUND: The Sorin Pericarbon Freedom Stentless aortic valve has the potential
      to provide superior hemodynamic function and durability. In this study we
      assessed the hemodynamic performance of this valve and its impact on LV-mass
      regression after aortic valve replacement. METHODS: 31 consecutive patients who
      received a Sorin Pericarbon Freedom Stentless aortic valve were analysed. Mean
      age of the patients (16 female and 15 male) was 64 +/- 17 years. Five patients
      had isolated aortic stenosis, three isolated aortic regurgitation and one
      combined aortic valve disease. Three patients had combined aortic and mitral
      valve disease, 14 patients concomitant coronary artery disease, one congenital
      aortic coarctation. Three patients had an acute aortic valve endocarditis. 18
      patients were classified as high-risk patients (mean EuroSCORE 9 +/- 2). Mean
      left ventricular ejection fraction was 52.5 +/- 15.0%. RESULTS: Valve sizes from
      21 mm to 29 mm were implanted. The valves were oversized by 2 mm compared to
      measurement. 16 patients received isolated aortic valve replacement, Three
      patients aortic valve replacement and mitral valve reconstruction. 12 patients
      had concomitant CABG. Three procedures were reoperations. Hospital mortality was
      6.4% (two patients). Both deaths occurred in high-risk patients and were not
      valve-related. Four patients had perioperative low-output-syndrome and needed
      IABP. After six months a follow up echocardiography was performed. Mean and peak
      gradients were 9.6 +/- 4.4 and 20.6 +/- 5.9 mmHg, respectively. Significant
      reduction of left ventricular hypertrophy (LV mass index 126.5 +/- 27.3 vs. 189.6
      +/- 45.3 g/m2, p = 0.0313) and improvement of the ejection fraction (58 +/- 9.8
      vs. 52.5 +/- 15.0%, p = 0.9749) as compared with preoperative valve. CONCLUSIONS:
      The hemodynamic performance of the Sorin Pericarbon Freedom Stentless aortic
      valve is excellent and the patient outcome is satisfying. However the
      implantation technique requires longer ischemic time, the prosthesis offers very
      satisfying hemodynamic function and accelerates probably the LV-mass regression
      in the mid term follow-up. Late performance and durability of the valve have to
      be assessed.

PMID- 14601330
TI  - WHO issues consensus document on the epidemiology of SARS.

PMID- 14601331
TI  - Recommended composition of influenza virus vaccines for use in the 2004 influenza
      season.

PMID- 14601332
TI  - General practitioners and community pharmacists: times they are a-changing.

PMID- 14601333
TI  - Postnatal depression and screening: too broad a sweep?

PMID- 14601334
TI  - Cannabis and the general practitioner--'going to pot'.

PMID- 14601335
TI  - Perceived interprofessional barriers between community pharmacists and general
      practitioners: a qualitative assessment.
AB  - BACKGROUND: There have been calls for greater collaboration between general
      practitioners (GPs) and community pharmacists in primary care. AIM: To explore
      barriers between the two professions in relation to closer interprofessional
      working and the extension of prescribing rights to pharmacists. DESIGN OF STUDY:
      Qualitative study. SETTING: Three locality areas of a health and social services
      board in Northern Ireland. METHOD: GPs and community pharmacists participated in
      uniprofessional focus groups; data were analysed using interpretative
      phenomenology. RESULTS: Twenty-two GPs (distributed over five focus groups) and
      31 pharmacists (distributed over six focus groups) participated in the study. The
      'shopkeeper' image of community pharmacy emerged as the superordinate theme, with
      subthemes of access, hierarchy and awareness. The shopkeeper image and conflict
      between business and health care permeated the GPs' discussions and accounted for
      their concerns regarding the extension of prescribing rights to community
      pharmacists and involvement inextended services. Community pharmacists felt such
      views influenced their position in the hierarchy of healthcare professionals.
      Although GPs had little problem in accessing pharmacists, they considered that
      patients experienced difficulties owing to the limited opening hours of
      pharmacies. Conversely, pharmacists reported great difficulty in accessing GPs,
      largely owing to the gatekeeper role of receptionists. GPs reported being unaware
      of the training and activities of community pharmacists and participating
      pharmacists also felt that GPs had no appreciation of their role in health care.
      CONCLUSION: A number of important barriers between GPs and community pharmacists
      have been identified, which must be overcome if interprofessional liaison between
      the two professions is to be fully realised.

PMID- 14601336
TI  - Patients' views of a pharmacist-run medication review clinic in general practice.
AB  - BACKGROUND: Reviewing elderly patients' medication is a requirement of the
      National Service Framework for Older People. Many general practitioners have
      insufficient time to review patients' medications in a consultation. Pharmacist
      review has been offered as an alternative and this will be a new experience for
      many patients. AIM: To ascertain patients' views of a pharmacist-conducted
      medication review clinic, run in their general practice surgery. DESIGN OF STUDY:
      Qualitative study using focus group interviews. SETTING: General practices in
      Leeds Health Authority area. METHOD: Patients aged 65 years and over, who had
      attended a medicine review clinic, took part in focus groups that were recorded
      and transcribed. Units of information representing an idea were identified and
      similar ideas were grouped together as themes. RESULTS: Patients had a number of
      prior beliefs about the clinic. Most patients knew that the clinic's purpose was
      to review repeat medication, to find out more about their medicines, and to ask
      questions about efficacy and side effects. Some patients were suspicious about
      the purpose of the clinic but others welcomed the opportunity to have an in-depth
      review and an explanation of their condition and its treatment; some patients did
      not accept advice or were disappointed that their expectations were not
      fulfilled. Most patients were happy to attend a yearly review but some expressed
      guilt about attending the surgery too frequently. CONCLUSION: Patients who
      attended the medication review clinics expressed a range of views about the
      service. Further research into patients' and carers' opinions about medicine
      review is needed to inform the development of these services.

PMID- 14601337
TI  - A qualitative study of the acceptability of routine screening of postnatal women
      using the Edinburgh Postnatal Depression Scale.
AB  - BACKGROUND: Screening for postnatal depression using the Edinburgh Postnatal
      Depression Scale (EPDS) has been widely recommended and implemented in primary
      care, although little is known about how acceptable it is to women. AIM: To
      explore the acceptability to women of postnatal screening by health visitors with
      the EPDS. DESIGN OF STUDY: Qualitative interview study. SETTING: Postnatal
      patients from 22 general practices within the area of Oxford City Primary Care
      Group. METHOD: Thirty-nine postnatal women from a purposive sample were
      interviewed, chosen on the basis of different general practices, EPDS results at
      eight weeks and eight months postnatal, and whether 'listening visits' were
      received. The interviews were analysed using the constant comparative method.
      RESULTS: Just over half of the women interviewed found screening with the EPDS
      less than acceptable, whatever their postnatal emotional health. The main themes
      identified were problems with the process of screening and, in particular, the
      venue, the personal intrusion of screening and stigma. The women interviewed had
      a clear preference for talking about how they felt, rather than filling out a
      questionnaire. CONCLUSION: For this sample, routine screening with the EPDS was
      less than acceptable for the majority of women. This is of concern, as universal
      screening with the EPDS for the detection of postnatal depression is already
      recommended and widespread in primary care.

PMID- 14601338
TI  - Cluster-randomised trial of risk communication to enhance informed uptake of
      cervical screening.
AB  - BACKGROUND: Women overestimate both population and individual risk of cervical
      cancer. This may contribute to the recognised excess screening frequency for low
      risk women. AIM: To investigate whether an individualized risk communication
      package could affect stated preferences for screening interval and actual
      screening behaviour. DESIGN: Pragmatic, practice-based cluster randomised
      controlled trial. SETTING: Twenty-nine practices (15 intervention, 14 control) in
      North Wales recruited 1890 women attending for cervical smears. METHOD: A risk
      communication package containing visual material was compared with normal
      practice. Practice nurses received training in its delivery. The short-term
      primary outcome was stated preference for screening interval; the long-term
      primary outcome was actual screening behaviour. RESULTS: In the short term,
      intervention arm women were significantly less likely to prefer a shorter than
      recommended interval (odds ratio [OR] = 0.51, 95% confidence interval [CI] = 0.41
      to 0.64; P < 0.0001). At the five-year follow-up, fewer women in the intervention
      arm had attended for screening sooner than their recommended recall. The
      magnitude of difference in excess screening interval preference and behaviour was
      similar, but behaviour had a wider confidence interval and a marginally non
      significant P-value (OR = 0.61, 95% CI = 0.36 to 1.03; P = 0.063). Better
      knowledge and more accurate risk perceptions were demonstrated, with an
      improvement in measures of anxiety. The extra cost per woman receiving the
      intervention was 6 Pounds. CONCLUSIONS: Women's perception of risk contributes to
      determining screening intervals in addition to practice factors. Simple risk
      information delivered in primary care affected women's stated preferences for
      tests. The impact on actual screening behaviour was more equivocal. Overall, the
      intervention showed a substantial benefit and any disbenefit can be ruled out.
      This approach to providing risk information could, at low cost, benefit other
      screening programmes and may relieve anxiety.

PMID- 14601339
TI  - Management of diagnostic uncertainty in children with possible meningitis: a
      qualitative study.
AB  - BACKGROUND: Neisseria meningitidis serogroup B is the most common cause of
      bacterial meningitis in children and young adults. Early recognition and prompt
      intervention with antibiotics are thought to be key to preventing serious
      complications. AIM: Explore how general practitioners evaluate and manage febrile
      children with possible meningitis or meningococcal septicaemia. DESIGN OF THE
      STUDY: Qualitative study using one-to-one, semi-structured interviews. SETTING:
      General practices in the Avon Health Authority district. METHOD: Twenty-six
      general practitioners were purposefully sampled, using a sampling frame to ensure
      a range of experience and practices in a variety of settings Data management and
      analysis were conducted using a grounded theory approach. RESULTS: Key themes to
      emerge were the effect that fear of meningitis has upon parents and general
      practitioners; the difficulties associated with reaching a diagnosis; and the
      existence of barriers to the use of guidelines and pre-hospital penicillin. When
      assessing a febrile child, participating general practitioners rarely thought
      that meningitis or meningococcal septicaemia were likely, but were aware that
      this was frequently the principal parental concern. They relied upon intuitive
      rather than systematic methods to distinguish serious from self-limiting
      conditions, rarely making a definitive diagnosis. Although concerned about
      'missed cases', interviewees doubted that current management could be improved.
      They questioned the assumption that guidelines could be sufficiently
      discriminating to be helpful and thought it unlikely that they would be followed
      in everyday clinical practice. Pre-hospital penicillin was only given if the
      diagnosis of meningitis or septicaemia was thought to be certain. CONCLUSIONS:
      There is a substantial gap in perception between primary and secondary care in
      the diagnostic and management approach to children who may have meningitis or
      meningococcal septicaemia. Until this is addressed, further attempts to improve
      early intervention in primary care are unlikely to succeed.

PMID- 14601340
TI  - Long-term outcome in open spina bifida.
AB  - BACKGROUND: Doctors need reliable data on outcome in order to help parents faced
      with difficult decisions about termination of an affected pregnancy or treatment
      after birth. AIM: To determine survival, health and lifestyle at the mean age of
      30 years in a complete cohort of adults born with open spina bifida. DESIGN OF
      STUDY: Prospective cohort study. PARTICIPANTS: Well-documented cohort of 117
      consecutive cases of open spina bifida whose backs were closed non-selectively at
      birth between 1963 and 1971. METHOD: Survivors (age range = 26 to 33 years) were
      surveyed by postal questionnaire and telephone interview. The main outcome
      measures were the health, independence and lifestyle of the survivors in terms of
      living in the community, driving a car and working in open employment. RESULTS:
      Ascertainment was 100%. Sixty (51%) had died, mainly the most disabled. Of the 57
      survivors, 84% had a cerebrospinal fluid (CSF) shunt, 70% had an IQ of 80 or
      more, 37% lived independently in the community, 39% drove a car, 30% could walk
      more than 50 metres and 26% were in open employment. However one-third (19) still
      needed daily care, three were on respiratory support, two were blind, two had
      diabetes mellitus, and one was on dialysis. Mortality, disability and achievement
      reflected the neurological deficit that had been recorded in infancy in terms of
      sensory level. Attainment and independence were reduced in those who had needed
      revision of CSF shunt. CONCLUSION: The survivors in this unselected cohort showed
      a wide range of outcome from apparent normality to very severe disability. This
      reflected both the extent of their original neurological deficit and events in
      the history of their CSF shunt.

PMID- 14601341
TI  - Cannabis use and the GP: brief motivational intervention increases clinical
      enquiry by GPs in a pilot study.
AB  - This preliminary test of a brief intervention designed to stimulate GP
      incorporation of cannabis enquiry was followed up after 2-3 months. Intervention
      comprised face-to-face discussion based on principles of motivational
      interviewing, with informational adjunct. Substantially more positive attitudes
      and greater clinical activity were observed following receipt of intervention.

PMID- 14601342
TI  - Positive test results motivate GPs to continue screening in a chlamydia
      prevalence study.
AB  - In this study, GPs predicted for each of their patients in a chlamydia prevalence
      study whether they would be infected or not. Prediction of infection did not
      correlate well with true infection risk. GPs who had infected patients at the
      beginning of the project included more patients afterwards than their colleagues
      who had only negative results. A rigid screening protocol is necessary to
      preserve GPs from choosing wrong candidates for screening and subsequently
      getting demoralized because no infections are diagnosed.

PMID- 14601343
TI  - Explaining variations in reported diabetes prevalence in general practice: how
      much variation is explained by differences between practice populations?
AB  - There are large variations in reported diabetes prevalence within United Kingdom
      (UK) populations. Linear regression was used to investigate whether population
      characteristics could explain the variation in prevalence between 19 practices
      with relatively complete diagnostic recording. Population obesity and South Asian
      ethnicity largely explained observed variation in prevalence (adjusted R2 =
      0.80). When adjusted for obesity and ethnicity, the deprivation score was no
      longer a predictor of diabetes prevalence. If true variation in prevalence
      between practices is largely predicted by population ethnicity and obesity, these
      population characteristics could be used to predict expected prevalence and to
      assess the completeness of practice registers.

PMID- 14601344
TI  - A service-academic partnership in primary care research: one practice's
      experience.
AB  - Further development of a strong research base for general practice is important
      if the profession is to respond appropriately to its central role in service
      provision. It can be difficult for general practitioners (GPs) who have not
      pursued an academic career path to make a significant contribution to research.
      The development of a service-academic partnership is described, together with an
      honest account of the difficulties encountered.

PMID- 14601345
TI  - Reconciling the head and the heart.

PMID- 14601346
TI  - What is a father?

PMID- 14601347
TI  - Practice, supervision, consultancy and appraisal: a continuum of learning.
AB  - I examine four different kinds of learning conversation: reflective practice,
      clinical supervision, work consultancy and performance appraisal. I propose that
      there is a close and reciprocal relationship between these kinds of conversation,
      and that they represent different aspects of a unified field, or continuum. I
      argue that appraisal should be seen as part of this learning continuum rather
      than as form of monitoring.

PMID- 14601348
TI  - Trust, performance management and the new GP contract.

PMID- 14601349
TI  - Alcohol and primary care--will an emphasis upon harm reduction engage general
      practitioners?

PMID- 14601350
TI  - The FIP study: a randomised, controlled trial of screening and recognition of
      psychiatric disorders.
AB  - BACKGROUND: Research on questionnaires as screening tools for psychiatric
      disorders has yielded conflicting results. AIM: To examine the effect of a
      routinely administered questionnaire on recognition of common psychiatric
      disorders in general practice. DESIGN OF STUDY: Randomised controlled trial.
      SETTING: Twenty-eight general practices in Aarhus County, Denmark. METHOD: Thirty
      eight general practitioners (GPs) and 1785 consecutive patients, aged 18-65 years
      old, presenting with a new health problem, participated. Before consultation,
      patients were screened using a brief screening questionnaire (SQ) including
      somatisation, anxiety, depression, and alcohol abuse scales. Patients were
      randomised to one of two groups: 900 questionnaires were disclosed and scored by
      the GPs, 885 were blinded. A stratified subsample of 701 patients was interviewed
      after the consultation using a standardised psychiatric research interview
      (SCAN). RESULTS: Overall the GPs' recognition rates were 14% (95% confidence
      interval [CI] = -2 to 30) better for depression and 35% (95% CI = 2 to 68) better
      for alcohol problems when SQs were disclosed. Recognition rates for anxiety
      improved 8% (95% CI = -9 to 26) overall. In the case of somatoform disorders,
      disclosure showed no effect overall. Among those with high SQ scores, however,
      disclosure increased recognition rates on any mental disorder evaluated.
      CONCLUSION: This study demonstrated limited usefulness for routine screening for
      common psychiatric disorders. However, findings suggest that the SQ may be useful
      for case-finding among a subgroup of patients with high SQ scores.

PMID- 14601351
TI  - PHASE: a randomised, controlled trial of supervised self-help cognitive
      behavioural therapy in primary care.
AB  - BACKGROUND: Common mental health problems account for up to 40% of all general
      practitioner (GP) consultations. Patients have limited access to evidence-based
      psychological therapies. Cognitive behavioural therapy self-help strategies offer
      one potential solution. AIM: To determine differences in clinical outcome,
      patient satisfaction and costs, between a cognitive behavioural-based self-help
      package facilitated by practice nurses compared to ordinary care by GPs for mild
      to moderate anxiety and depression. DESIGN OF STUDY: Randomised controlled trial.
      SETTING: Seventeen primary healthcare teams. METHOD: Patients presenting to their
      GP with mild to moderate anxiety and/or depression were recruited to the study
      and randomised to receive either a self-help intervention facilitated by practice
      nurses or ordinary care. The self-help intervention consisted of up to three
      appointments: two 1 week apart and a third 3 months later. There were no
      restrictions on ordinary care. RESULTS: Intention-to-treat analysis showed that
      patients treated with practice nurse-supported cognitive behavioural therapy self
      help attained similar clinical outcomes for similar costs and were more satisfied
      than patients treated by GPs with ordinary care. On-treatment analysis showed
      patients receiving the facilitated cognitive behavioural therapy self-help were
      more likely to be below clinical threshold at 1 month compared to the ordinary
      care group (odds ratio [OR] = 3.65, 95% confidence interval [CI] = 1.87 to 4.37).
      This difference was less well marked at 3 months (OR = 1.36, 95% CI = 0.52 to
      3.56). CONCLUSION: Facilitated cognitive behavioural self-help may provide a
      short-term cost-effective clinical benefit for patients with mild to moderate
      anxiety and depression. This has the potential to help primary care provide a
      choice of effective psychological as well as pharmacological treatments for
      mental health problems.

PMID- 14601353
TI  - The reducing incidence of respiratory tract infection and its relation to
      antibiotic prescribing.
AB  - BACKGROUND: There is good evidence of reduced prescribing of antibiotics in
      recent years, but the reason for this has not been established. AIM: To study the
      incidence of respiratory tract infections presenting to general practitioners
      (GPs) in England and Wales in relation to the incidence of other infections and
      to the prescription of antibiotics. SETTING: Sentinel practices in England and
      Wales who contribute to the Weekly Returns Service (WRS) of the Royal College of
      General Practitioners. DESIGN: Time-series analysis of disease incidence data
      reported by the practices and of antibiotic prescription data from the
      Prescription Pricing Authority (PPA) during the years 1994-2000. METHOD:
      Incidence data reported weekly from 73 practices in England and Wales, serving a
      population of 600,000, for acute respiratory tract infections, otitis media,
      infectious mononucleosis, shingles, urinary tract infections, and skin
      infections, were consolidated into quarterly datasets and examined graphically
      for evidence of secular and seasonal trends. Trends in antibiotic prescription
      items (data for England only were supplied by the PPA) were examined for
      association after adjustment for seasonal variation. RESULTS: The incidence of
      respiratory tract infections and antibiotic prescribing showed virtually
      identical seasonal variation, with both declining from 1995: respiratory tract
      infections by 48% in winter and 38% in summer, and antibiotic prescriptions by
      34% and 21%, respectively. Trends in both were very highly correlated. The
      incidence of shingles and skin infections was constant. The incidence of urinary
      tract infections declined by 10%. The incidence of otitis media in children and
      acute bronchitis in the elderly followed the all-age trend in the reduction of
      respiratory tract infections. CONCLUSION: The considerable reduction in the
      incidence of respiratory tract infections between 1995 and 2000 is the main
      reason for the decline in antibiotic prescribing rather than changing prescribing
      thresholds for antibiotics.

PMID- 14601352
TI  - A double-blind, randomised, placebo controlled study of venlafaxine XL in
      patients with generalised anxiety disorder in primary care.
AB  - BACKGROUND: Generalised anxiety disorder (GAD) is one of the commonest anxiety
      disorders and is treated almost entirely in primary care. Most recent studies
      performed in GAD have excluded depression for regulatory reasons. As GAD is
      usually a co-morbid disease, often co-existing with depression, the results from
      recent studies have only limited relevance to the naturalistic population. This
      study was set up to investigate venlafaxine XL in a more naturalistic population
      of patients with GAD. AIM: To assess the efficacy of venlafaxine XL in patients
      with generalised anxiety disorder with and without co-morbid depression. DESIGN
      OF STUDY: Double-blind, randomised, placebo controlled, parallel-group, 24-week
      study. SETTING: Primary care in the UK. METHODS: Patients enrolled in the study
      were over 18 years old, met DSM-IV criteria for GAD, and had a score of 20 or
      more on the Hamilton Anxiety Scale (HAM-A). A score of more than 23 on the
      Montgomery Asberg Depression Rating Scale (MADRS) excluded patients. Eligible
      patients were randomised to receive 75 mg of venlafaxine or a matching placebo.
      After 2 weeks the dose could be doubled if the physician considered the response
      to be poor. The study duration was 24 weeks. RESULTS: 244 patients were enrolled,
      with 122 randomised to the placebo and 122 to venlafaxine. Baseline
      characteristics were similar for both groups, each having a mean total HAM-A
      score at baseline of 28. The difference from the placebo group at 24 weeks on the
      total HAM-A score was 2.1 points (95% 0 to 4.2), which was statistically
      significant (P = 0.05). Remission rates at week 24 were 27.9% for the venlafaxine
      XL group and 18.9% for placebo group (P = 0.11). CONCLUSION: Venlafaxine was
      efficacious in the treatment of patients with GAD with and without depression
      over a 24-week period.

PMID- 14601354
TI  - Increased mortality among women with Rose angina who have not presented with
      ischaemic heart disease.
AB  - BACKGROUND: Little is known about the clinical importance of disease that is not
      presented to healthcare services. AIM: To determine the 5-year mortality among
      those with angina symptoms, known or not known by their general practitioner (GP)
      to have ischaemic heart disease (IHD). DESIGN: A prospective cohort study.
      SETTING: The study was conducted in the United Kingdom as part of the Royal
      College of General Practitioners' Oral Contraception Study. METHOD: In 1994-1995
      women (n = 11,797) still under GP observation were sent a questionnaire that
      inquired about their smoking habits, other lifestyle issues, general health, and
      selected symptoms (including chest pain, assessed using the Rose angina
      questionnaire). The main outcome measure was the chances (odds) of dying during
      the next 5 years, among those with and without exertional chest pain, Rose angina
      or Rose myocardial infarction (MI), stratified by documented history of IHD.
      RESULTS: Overall, the lifetime prevalence of any exertional chest pain was 10.1%
      (95% confidence interval [CI] = 9.5 to 10.8); grade I Rose angina was 6.1% (95%
      CI = 5.6 to 6.6); grade II Rose angina was 1.3% (95% CI = 1.1 to 1.6); and Rose
      MI was 4.4% (95% CI = 4.0 to 4.9). The prevalence of each condition tended to
      increase with age, social class, parity, body mass index, and documented history
      of IHD. The proportion of women documented as having IHD was 23% among those with
      any exertional chest pain, 21.7% for grade I Rose angina, 37.7% for grade II Rose
      angina, and 31.4% for Rose MI. Compared to women without Rose angina,
      significantly higher odds ratios for all-cause mortality were observed among
      women with grade I Rose angina and no documented history of IHD (adjusted odds
      ratio [AOR] = 1.71, 95% CI = 1.05 to 2.79); those with grade II Rose angina and
      documented IHD (AOR = 3.94, 95% CI = 1.58 to 9.83); and women with grade II Rose
      angina and no documented history of IHD (AOR = 3.35, 95% CI = 1.47 to 7.62).
      CONCLUSIONS: Women with angina symptoms that have not been documented by their GP
      appear to have an increased risk of future mortality. Research is needed to
      determine the best way of identifying and managing these individuals.

PMID- 14601355
TI  - Predictors for the white coat effect in general practice patients with suspected
      and treated hypertension.
AB  - BACKGROUND: Ambulatory blood pressure monitoring was introduced more than 40
      years ago and is accepted as a clinically useful method to evaluate the white
      coat effect in patients with suspected and established hypertension. AIM: To
      study the differences between blood pressure readings taken in the physician's
      office in the primary healthcare setting, and ambulatory readings, and to find
      possible predictors. DESIGN OF STUDY: Prospective study. SETTING: Two primary
      healthcare centres in Norway. METHOD: The study included 221 patients, 107 of
      whom were on antihypertensive treatment, and 114 of whom were under investigation
      for possible hypertension. Differences between blood pressure readings taken in
      the physician's office and ambulatory readings were calculated. Independent
      predictors for the white coat effect were calculated using linear regression
      analysis. RESULTS: The difference between blood pressure readings taken in the
      office and ambulatory readings was 27 mmHg systolic and 11 mmHg diastolic. For
      the systolic readings, the following factors were independent predictors of the
      amount of the white coat effect: mean blood pressure, age, history of smoking,
      family history of cardiovascular disease, and antihypertensive treatment. For the
      diastolic readings, they were: mean blood pressure, history of smoking, and sex
      of the patient (with this being most significant for women). CONCLUSION:
      Ambulatory blood pressure measurement is of significant value in identifying
      patients with white coat hypertension. It can be an important supplement for use
      in the diagnosis and follow-up of patients with hypertension in general practice.

PMID- 14601356
TI  - Is ambulatory blood pressure monitoring cost-effective in the routine
      surveillance of treated hypertensive patients in primary care?
AB  - Achieving target levels of office and/or ambulatory blood pressure readings among
      treated hypertensive patients is an important aspect of cardiovascular disease
      prevention. Although office blood pressure measurement is simple and convenient,
      ambulatory blood pressure monitoring is especially useful for identifying
      patients with 'white coat' hypertension, in whom falsely raised office blood
      pressure recordings often lead to unnecessary return visits and additional
      treatment. Office and ambulatory blood pressure control was compared in 374
      treated hypertensive patients in a single general practice, and the costs of
      performing annual ambulatory blood pressure measurements were compared with
      potential clinical savings. Ambulatory blood pressure monitoring detected 115
      (31%) patients who fulfilled the British Hypertension Society target for
      ambulatory but not office blood pressure, i.e. white coat hypertension, and 21
      patients apparently controlled by office but not ambulatory blood pressure
      criteria. In economic modelling, the capital, maintenance and user costs of
      ambulatory blood pressure monitoring (13,790 Pounds per year) were partly offset
      by fewer follow-up visits and second-line treatments in the group with white coat
      hypertension (there were modelled savings of 10,178 Pounds). Thus, ambulatory
      blood pressure monitoring identified a much larger number of treated hypertensive
      patients with adequate blood pressure control at an extra net cost of 3612 Pounds
      per year.

PMID- 14601357
TI  - Factors associated with patients' trust in their general practitioner: a cross
      sectional survey.
AB  - This study aimed to identify factors that are associated with patients' overall
      trust in their general practitioner (GP). A survey of patients in ten general
      practices in the East Midlands was conducted. Most patients (76%) reported high
      levels of trust in their GP. Regression analysis showed that measures of the
      quality of the GP-patient relationship (GP-patient communication, interpersonal
      care, and knowledge of the patient) were strongly associated with trust in a
      patient's usual GP, whereas patients' reports of duration of registration with
      the practice, and proportion of visits to the usual GP were not.

PMID- 14601358
TI  - Egg allergy and MMR vaccination.

PMID- 14601359
TI  - Developing a primary care-based stroke model: the prevalence of longer-term
      problems experienced by patients and carers.
AB  - BACKGROUND: Over the last two decades, the need for a longer-term perspective to
      stroke management has become increasingly recognised. This paper reports a
      component of a larger project aimed at developing a systematic, primary care
      based service for stroke aftercare. AIM: To identify the types and prevalence of
      longer-term problems experienced by stroke patients and their carers in the
      United Kingdom (UK). METHOD: Systematically identified quantitative surveys
      reporting the prevalence of long-term stroke-related problems were reviewed and
      the findings extracted and interpreted against a patient and carer defined
      classification system, identified during an earlier review of the qualitative
      stroke literature. RESULTS: Twenty-seven UK surveys, including approximately 6000
      patients and 3000 carers, and two literature reviews were identified by the
      search methods. Most of the problem areas identified in the qualitative stroke
      literature review were reported in the quantitative surveys and an additional two
      problems were identified (falls and sexual problems). The prevalence of problems
      in each of the areas was as follows: 19% to 62% for emotional problems; 18% to
      46% for social problems; 13% to 77% for service issues; 18% to 88% for poor
      communication; 33% to 100% for transfer of care; and 10% to 73% for other areas.
      CONCLUSION: This review confirms the findings and recommendations from earlier
      work about the need for a longer-term holistic approach to the rehabilitation of
      stroke patients and support for carers. Having established the nature and
      frequency of the main problems experienced by stroke patients and their carers,
      the appropriate evidence-based interventions need to be identified and
      consolidated into a stroke service, facilitated by a robust patient-assessment
      process.

PMID- 14601360
TI  - Methadone treatment in an intermediate care setting?

PMID- 14601361
TI  - Financing defibrillators in general practice.

PMID- 14601362
TI  - Screening for domestic violence.

PMID- 14601363
TI  - Can GPs and PALS be friends?

PMID- 14601364
TI  - [From Anesthesiology to the Anesthesiologies: vocation and specialization].

PMID- 14601365
TI  - [Predictive capability of the TCI Diprifusor system in patients with terminal
      chronic renal insufficiency].
AB  - OBJECTIVE: To evaluate the predictive capability of a target-controlled infusion
      (TCI) system in patients with terminal chronic renal failure by comparing real
      drug concentrations with predicted concentrations. METHODS: Forty ASA II-III
      patients undergoing kidney transplants were enrolled and grouped by age: group A
      18-54 years old and group B 55-80 years old. Propofol was administered through
      the Diprifusor TCI system (Astra Zeneca) with the target concentration of
      propofol for induction set at 3 micrograms/mL for group A patients and 2.5
      micrograms/mL for group B patients. Arterial blood samples were taken for
      analysis of drug concentrations at the following times: 2 and 5 minutes after
      starting the infusion; immediately after the incision; before and 5 minutes after
      increasing or decreasing the target concentration > 25%; before and 5 minutes
      after switching off the perfusion for surgery; upon eye opening; and 30 minutes
      after switching off the infusion pump. The predictive capability of the system
      was determined by performance error (PE). We calculated bias (%, median PE) and
      accuracy (%, median absolute PE). RESULTS: Twenty group A and 20 group B patients
      were studied. The median PEs in groups A and B, respectively, were -3.45 (-20.3
      28.4) and -1.1 (-19.7-15.4). Median absolute PEs were 21.2 (11.9-45.1) and 16.3
      (11.5-27.4), respectively. CONCLUSIONS: The results indicate that the predictive
      capability of the Diprifusor pharmacokinetic model is acceptable in patients with
      terminal kidney failure, given the minor bias of 10% to 20% and the degree of
      accuracy between 20% and 40%.

PMID- 14601366
TI  - [Usefulness of tranexamic acid in cranial remodeling surgery].
AB  - OBJECTIVES: To assess the usefulness of tranexamic acid (TA) in pediatric cranial
      remodeling surgery, by analyzing its effects on bleeding and transfusion
      requirements, number of days of cranial drainage required, and time spent in the
      postoperative recovery unit. MATERIAL AND METHOD: A single-blind, controlled
      study was designed with 20 patients (10 cases and 10 controls) randomly assigned
      to receive or not receive 15 mg/kg of intravenous TA upon anesthetic induction,
      every 4 hours during surgery, and every 8 hours throughout the 48 hours after
      surgery. Variables analyzed were results of blood tests, blood loss, volume
      transfused, time in the recovery unit, and complications related to TA infusion.
      RESULTS: The group treated with TA experienced less bleeding during surgery than
      did the controls (199 +/- 60 vs 290 +/- 43 mL) and had less need of
      intraoperative (176 +/- 104 vs 206 +/- 70 mL) and postoperative transfusion (9 +/
      28 vs 52 +/- 72 mL) 24 hours after surgery. TA group patients also spent less
      time in the recovery unit (60 +/- 14 vs 72 +/- 11 hours). Blood test variables in
      TA-treated children were also better 24 hours after surgery with regard to
      hemoglobin (12.1 +/- 2 vs 11.6 +/- 1.3 mg/dL) and platelet (261 +/- 68.5 vs 181.6
      +/- 58.1 platelets/mm3) concentrations, and cephalin time (33 +/- 12 vs 49 +/- 16
      seconds). No complications related to TA treatment were observed. CONCLUSIONS: TA
      can reduce perioperative bleeding in the context of pediatric cranial remodeling
      surgery. TA-treated patients have less need of transfusion and this may reduce
      the rate of related complications as well a make care more efficient.

PMID- 14601367
TI  - [Erythropoietin alone or as an adjuvant for the autologous blood donation program
      in major orthopedic surgery].
AB  - BACKGROUND: Patients with anemia undergoing elective joint replacement are often
      excluded from preoperative autologous donation (PAD). The purpose of this study
      was to compare the efficacy of preoperative erythropoietin (epoetin alpha) as an
      adjuvant treatment to PAD versus preoperative erythropoietin alfa alone in
      patients with mild anemia undergoing major orthopedic surgery. PATIENTS AND
      METHODS: The study enrolled 75 patients scheduled for total joint arthropalsty of
      the hip or knee or spinal surgery and with a hemoglobin (Hb) concentration
      between 10 and 13 g/dL. Group 1 patients were assigned to receive weekly doses of
      subcutaneous epoetin alpha (40,000 IU) 21, 14, and 7 days before surgery and to
      participate in the PAD program; group 2 patients were excluded from the PAD
      program and received 2 doses of epoetin alpha every week over the same period.
      RESULTS: Group 1 (n = 39) and group 2 (n = 36) were similar with respect to
      patient characteristics, biological parameters, and surgical procedures, In group
      1, mean preoperative Hb rose fom 12.5 g/dL to 12.8 g/dL, patients received a mean
      5.1 doses of epoetin alpha, and they gave a mean 1.9 units of autologus blood and
      1 received allogenic blood. In group 30.7% received transfusions of autologous
      blood and 1 received allogenic blood. In group 2, preoperative Hb increased from
      11.7 g/dL to 13.5 g/dL, patients received 3.8 doses of epoetin alpha, and 3 were
      transfused with allogenic blood (P > 0.05). CONCLUSION: Epoetin alpha alone and
      erythropoietin as a adjuvant to a PAD program are equally effective in reducing
      allogenic transfusion during hip and knee arthroplasty and spinal column surgery
      of up to 3 spaces.

PMID- 14601368
TI  - [Gastrointestinal tonometry: a new tool for the anesthesiologist].
AB  - Intestinal hypoperfusion is among the factors implicated in sepsis and multiorgan
      failure. Splanchnic blood flow may be sacrificed to maintain supply to vital
      organs, even when hemodynamic alterations are minor. The sensitivity of invasive
      hemodynamic monitoring for detecting intestinal hypoperfusion is low. This paper
      aims to review current knowledge about indirect measurement of splanchnic
      perfusion by way of gastrointestinal tonometry. We review the pathophysiology of
      ischemic intestinal lesions, the basis for gastrointestinal tonometry, and the
      method. Finally we discuss clinical applications (early diagnosis of ischemic
      colitis and ischemia of the flap after esophageal reconstruction, weaning from
      mechanical ventilation, abdominal compartment syndrome, liver transplant, heart
      surgery, prognostic factors and care of the critically ill patient). An adequate
      understanding of this monitoring technique and management of information it
      provides can give an early warning of the intestinal hypoperfusion that precedes
      other serious systemic complications.

PMID- 14601369
TI  - [Heart arrest during fibro-bronchoscopic intubation in a patient with
      parapharyngeal space neoplasia].
AB  - A 37-year-old woman a diagnosis of squamous carcinoma of the tongue and a history
      of partial/hemiglossectomy with cervical lymphadenectomy and postoperative
      radiotherapy was scheduled for biopsy under general anesthesia given the
      suspicion of local recurrence. She underwent routine preparation for intubation
      with a fiberoptic bronchoscope with topical anesthesia of mucosal tissue without
      sedation. Syncope and asystole presented suddenly during intubation and external
      cardiopulmonary resuscitation and difficult ventilation through a face mask were
      necessary. She was finally intubated using a retrograde technique and recovered
      heartbeat after 20 minutes. No neurological sequelae were observed over the next
      few days. The etiologic diagnosis of this rare complication was later based on
      the appearance of the characteristic clinical profile of glossopharyngeal
      neuralgia-asystole syndrome in combination with parapharyngeal space lesion
      syncope syndrome; magnetic resonance findings of extensive neoplastic invasion of
      the space confirmed the diagnosis. Endotracheal intubation with a fiberoptic
      bronchoscope plays an important role in the management of the anticipated
      difficult airway. It is safe in the awake patient and facilitates the
      identification of structures, particularly when there are anatomical alterations
      due to neoplastic invasion, surgery, or radiotherapy. In the patient we describe,
      however, stimulation caused asystole.

PMID- 14601370
TI  - [Bradycardia-tachycardia syndrome during spinal anesthesia].
AB  - A 78-year-old man developed bradycardia with decreased level of consciousness
      followed by sinus arrest during femoropopliteal bypass surgery under subarachnoid
      anesthesia. Early in the recovery period, a similar clinical picture developed,
      with bradycardia but no change in level of consciousness. Sinus node automaticity
      or sinoatrial conduction abnormalities were suspected, and a 24-hour Holter
      electrocardiogram revealed bradycardia-tachycardia syndrome. The patient was
      prescribed amiodarone and anticoagulant therapy with acenocoumarol; no further
      episodes occurred during hospitalization. Bradycardia-tachycardia syndrome is a
      sinus node disorder that manifests intermittently. It can become apparent during
      or shortly after surgery, leading to problems of differential diagnosis.

PMID- 14601371
TI  - [3 cases of sedation and analgesia using propofol and remifentanil for labor].
AB  - Three women in labor for whom epidural analgesia was contraindicated--2 with
      sepsis (pylonephritis and chorioamnionitis) and 1 with sacral agenesia--were
      provided intravenous analgesia with propofol (0.4-1.2 mg/kg/h) and remifentanil
      (0.033-0.1 microgram/kg/min plus boluses of 20 micrograms controlled by the
      patient) with oxygen supplementation. Heart rate, noninvasive blood pressure,
      maternal oxygen saturation and fetal heart rate were monitored. Maternal
      satisfaction, quality of analgesia, maternal side effects (sedation, depression,
      breathing, muscle rigidity, nausea, and vomiting) and fetal side effects (heart
      rate variability and Apgar score) were evaluated. We conclude that in cases where
      epidural analgesia is contraindicated, intravenous perfusion of low doses of
      propofol and remifentanil can provide a valid alternative for analgesia during
      labor.

PMID- 14601372
TI  - [Levosimendan as inotropic support during coronary surgery with extracorporeal
      circulation in a patient with severely depressed ventricular function].

PMID- 14601373
TI  - [Design of a care plan for the difficult airway in a university hospital].

PMID- 14601374
TI  - [Coronary spasm during anesthesia induction].

PMID- 14601375
TI  - [Selective ventilation via tracheostomy in a patient with mediastinitis and
      Ludwig's angina].

PMID- 14601376
TI  - [Epidural anesthesia for percutaneous vertebroplasty].

PMID- 14601377
TI  - [Postpartum paraparesis caused by probably polymyositis after obstetric epidural
      analgesia].

PMID- 14601378
TI  - [Therapeutic approach to paresthetic meralgia].

PMID- 14601379
TI  - [Psychological atmosphere during childhood and level of social functioning in
      adulthood].

PMID- 14601380
TI  - [Are old medications abandoned for nothing?].

PMID- 14601381
TI  - [Adverse effects of second generation antipsychotic agents].

PMID- 14601382
TI  - [What kind of exercise will promote health? Consensus meeting assessment about
      the dose-effect relationship of exercise and health].

PMID- 14601383
TI  - [Radiological classification and nomenclature of lumbar intervertebral disc
      disorders].

PMID- 14601384
TI  - [Suicide mortality in Finland during 1979-2001].

PMID- 14601385
TI  - [Primary hyperoxaluria].

PMID- 14601386
TI  - [Abnormal respiration in a young infant].

PMID- 14601387
TI  - [A complementary viewpoint concerning pain].

PMID- 14601388
TI  - [Painter Hannu Vaisanen].

PMID- 14601389
TI  - [Good and bad medicalisation].

PMID- 14601390
TI  - [Human being in a grip of medicalisation].

PMID- 14601391
TI  - [From the roots of medicalisation to today's situation].

PMID- 14601392
TI  - [Physician and medicalisation].

PMID- 14601393
TI  - [Paramedicalisation].

PMID- 14601394
TI  - [Genetization].

PMID- 14601395
TI  - [Good and bad aspects of the medicalisation of aging].

PMID- 14601396
TI  - [Whom does death belong to?].

PMID- 14601397
TI  - [Life is dangerous: even a risk has a risk].

PMID- 14601398
TI  - [How the features of three-dimensional structure of aspartate proteinases
      determine their properties].
AB  - There is given a brief account of the specific interactions of some amino acid
      residues in aspartic proteases of both higher organisms and retroviruses that
      determine their important properties: an anomalously low isoelectric point of
      pepsin and its stability at pH close to unity; the ability of one of the carboxyl
      groups in the active site of proteases of higher organisms to retain charged
      state at any pH value and protonated state of another carboxyl, which is
      necessary for their enzymatic activity. It is also explained how such states can
      be induced in retroviral proteases.

PMID- 14601399
TI  - [Tobacco etch virus proteinase: crystal structure of the active enzyme and its
      inactive mutant].
AB  - Tobacco Etch Virus Protease (TEV protease) is widely used as a tool for
      separation of recombinant target proteins from their fusion partners. The crystal
      structures of two mutants of TEV protease, active autolysis-resistant mutant TEV
      S219D in complex with the proteolysis product, and inactive mutant TEV-C151A in
      complex with a substrate, have been determined at 1.8 and 2.2 A resolution,
      respectively. The active sites of both mutants, including their oxyanion holes,
      have identical structures. The C-terminal residues 217-221 of the enzyme are
      involved in formation of the binding pockets S3-S6. This indicates that the
      autolysis of the peptide bond Met218-Ser219 exerts a strong effect on the fine
      tuning of the substrate in the enzyme active site, which results in considerable
      decrease in the enzymatic activity.

PMID- 14601400
TI  - [Molecular mechanisms of stabilizing proteolytic enzymes. Model of a thermolysin
      like microbial metalloproteinase].
AB  - The molecular mechanisms that ensure the stability of proteolytic proteins are
      discussed. The autolytic pathway of protease degradation is emphasized.
      Experiments aimed at increasing the thermal stability of thermolysin-like
      metalloproteases are comprehensively described.

PMID- 14601401
TI  - [Structure-functional features of homologous domains of angiotensin-converting
      enzyme].
AB  - Somatic angiotensin-converting enzyme (ACE) consists of two homologous domains,
      each of them containing an active site. Differences in substrate specificities
      and affinity to inhibitors of the active sites of the two domains of bovine ACE
      are described. The ACE domains demonstrate different thermostability, and the
      reasons for this difference are analyzed. A structural model of the ACE domains
      is suggested, which allows us to reveal the structural subdomain important for
      the protein stability and localize the hydrophobic and the carbohydrate-binding
      sites.

PMID- 14601402
TI  - [Interaction of alpha-chymotrypsin with dimethylsulfoxide: a change of substrate
      could change the mechanism of interaction].
AB  - The kinetic behavior of alpha-chymotrypsin was studied in water-DMSO mixtures at
      concentrations of the organic solvent that do not cause irreversible denaturation
      of the enzyme. Various substrates (N-substituted derivatives of L-tyrosine) were
      found to display substantially different kinetic patterns of interaction with
      alpha-chymotrypsin, which can be described by totally different kinetic schemes.
      The differences were ascribed to competition between the N-acyl group of the
      substrate and the DMSO molecule at the S2-site of substrate binding to the active
      site of the enzyme.

PMID- 14601403
TI  - [Proteolysis coupled with ATP. Regulation of activity of proteolytic centers of
      Escherichia coli lon protease].
AB  - Regulation of activity of the proteolytic sites of Lon protease was studied. It
      was found that ATP-Mg has the properties of a noncompetitive activator of
      peptidase sites. The processive mechanism of the hydrolysis of protein substrates
      by Lon protease was experimentally confirmed under the conditions of ATP
      hydrolysis. It was shown that the oligomeric state of the enzyme is the necessary
      prerequisite for the processive proteolysis by the native Lon protease. The study
      of the properties of the mixed mutant Lon-K362Q/S679A confirmed the existence of
      the intra- and intersubunit pathways of signal transduction from the ATPase to
      proteolytic sites. The mutual influence of substrates of Lon protease was
      studied, and the existence of cooperative interactions between the peptidase
      sites in the oligomeric enzyme was suggested.

PMID- 14601404
TI  - [Aptameric DNA--a new type of thrombin inhibitor].
AB  - The formation of complexes between various thrombin preparations and a 30-mer
      aptamer DNA was comparatively studied, and a correlation between the complex
      formation and the fibrinogen-hydrolyzing activity of thrombin was found. The
      aptamer DNA was shown to inhibit the fibrin formation from fibrinogen.

PMID- 14601405
TI  - [Role of proteinase inhibitors in potato protection].
AB  - Mechanical damage or infection of potatoes with Phytophthora infestans caused an
      accumulation of only serine protease inhibitors in exudates of potato tubers.
      Among them, proteins prevailed that are structurally similar to those present in
      healthy tubers: a 22-kDa trypsin inhibitor, a 21-kDa serine protease inhibitor
      consisting of two polypeptide chains, and a 8-kDa potato chymotrypsin I inhibitor
      produced de novo. The accumulated proteins inhibited the growth of hyphae and
      germination of zoospores of P. infestans. Treatment with elicitors, jasmonic and
      arachidonic acids, intensified the accumulation of these inhibitors in tubers in
      response to the wound stress, whereas salicylic acid blocked this process. These
      results suggest that the lipoxygenase metabolism plays a substantial role in
      signal transduction of the protective system of resting potato tubers.

PMID- 14601406
TI  - [Effect of the antioxidant ionol on proteolytic apparatus of aging coleoptiles of
      wheat seedlings grown in light].
AB  - The dynamics of changes in total proteolytic activity and activities of various
      groups of proteases in the coleoptiles of 3- to 12-day-old wheat seedlings grown
      in light with and without antioxidant BHT (2,6-di-tert-butyl-4-methylphenol) was
      studied. It was established that the specialized proteases that easily hydrolyze
      specific synthetic substrates and the enzymes actively hydrolyzing histone H1
      dominate in young coleoptiles of 3- to 4-day-old seedlings. Proteases that
      degrade equally well the majority of the studied substrates are accumulated in
      the cells of old coleoptiles of 11- to 12-day-old seedlings. Under the effect of
      BHT, the plants grown in light (in comparison with etiolated seedlings)
      demonstrated a somewhat changed dynamics of proteolytic activity in young
      coleoptiles and the disappearance of proteases active toward histone H1. An
      inhibitory analysis revealed a relative domination of cysteine proteases in young
      coleoptiles at the initial development stage of seedlings, whereas the fraction
      of serine proteases markedly increased in old coleoptiles. We presume that the
      revealed quantitative and qualitative changes in the proteolytic apparatus of the
      coleoptile cells induced by BHT may be largely responsible for the retardant and
      geroprotective effect of this antioxidant in plants.

PMID- 14601407
TI  - [Role of phosphorylation of myosin and actin-binding proteins in endothelial
      permeability induced by thrombin].
AB  - The thrombin-induced dysfunction of the barrier function of the blood vessel
      endothelium, which manifests itself in increased permeability, is largely
      mediated via the initiation of specific receptors that trigger multiple signaling
      cascades, including the activation of some protein kinases and the
      phosphorylation of their cytoskeletal targets. The role of the phosphorylation of
      myosin and actin-binding proteins in the thrombin-induced permeability of the
      endothelium and possible mechanisms of the regulation of the endothelium barrier
      function are discussed.

PMID- 14601408
TI  - [Regulation of caspase activity in apoptosis].
AB  - Intracellular cysteine aspartate-specific proteases (caspases) play both
      signaling and effector roles in realizing the program of cell death. Caspases
      function as proteolytic cascades unique for each cell type and signal triggering
      apoptosis. All parts of the proteolytic cascades are duplicated and controlled by
      feedback signals. Amplification cycles between pairs of caspases (the third and
      the sixth, the ninth and the third, the twelfth and the sixth, and others) help
      multiply the initial apoptotic signal. The presence of physiological inhibitors
      of apoptosis that directly interact with caspases creates a multilevel regulatory
      network of apoptosis in cell. The caspase proteolytic cascades are also regulated
      by sphingolipid secondary messengers, among them ceramide, sphingosine, and their
      phosphates. Moreover, an association of the caspase signaling with ubiquitin
      dependent proteolysis is shown in cells. In particular, the use of extracellular
      activators and inhibitors of caspases allows irreversible activation of apoptosis
      in tumor cells or the prevention of neuron death in neurodegenerative diseases.

PMID- 14601409
TI  - [Modified proteinases in peptide synthesis in organic media].
AB  - We showed that modified proteases could catalyze synthesis of a wide variety of
      peptides of various lengths and structures both in solution and on solid phase in
      organic solvents. The following modified proteases were studied as catalysts for
      enzymatic peptide synthesis in polar organic solvents (acetonitrile,
      dimethylformamide, and ethanol): pepsin sorbed on celite, a noncovalent complex
      of subtilisin with sodium dodecylsulfate, and subtilisin or thermolysin
      covalently immobilized on a cryogel of polyvinyl alcohol. The use of the
      noncovalent complex of subtilisin with sodium dodecylsulfate and immobilized
      subtilisin is especially promising for the segment condensation of peptide
      fragments containing residues of trifunctional amino acids with unprotected
      ionogenic groups in side chains, such as Lys, Arg, His, Glu, and Asp.

PMID- 14601410
TI  - [Native and modified subtilisin 72 as a catalyst of peptide synthesis in media
      with low water content].
AB  - The catalytic efficiencies of native subtilisin, its noncovalent complex with
      polyacrylic acid, and the subtilisin covalently immobilized in a cryogel of
      polyvinyl alcohol were studied in the reaction of peptide coupling in mixtures of
      organic solvents with a low water content in dependence on the medium
      composition, reaction time, and biocatalyst concentration. It was established
      that, in media with a DMF content > 80%, the synthase activity of modified
      subtilisins is higher than that of the native subtilisin. The use of N
      acylpeptides with a free carboxyl group was found to be possible in organic
      solvents during the enzymatic synthesis catalyzed by both native and immobilized
      subtilisin. A series of tetrapeptide p-nitroanilides of the general formula Z-Ala
      Ala-Xaa-Yaa-pNA (where Xaa is Leu, or Glu and Yaa is Phe or Asp) was obtained in
      the presence of immobilized enzyme in yields of 70-98% in DMF-MeCN without any
      activation of the carboxyl component and without protection of side ionogenic
      groups of polyfunctional amino acids.

PMID- 14601411
TI  - Benthic foraminifera (Protista) as tools in deep-water palaeoceanography:
      environmental influences on faunal characteristics.
AB  - Foraminiferal research lies at the border between geology and biology. Benthic
      foraminifera are a major component of marine communities, highly sensitive to
      environmental influences, and the most abundant benthic organisms preserved in
      the deep-sea fossil record. These characteristics make them important tools for
      reconstructing ancient oceans. Much of the recent work concerns the search for
      palaeoceanographic proxies, particularly for the key parameters of surface
      primary productivity and bottom-water oxygenation. At small spatial scales,
      organic flux and pore-water oxygen profiles are believed to control the depths at
      which species live within the sediment (their 'microhabitats'). Epifaunal/shallow
      infaunal species require oxygen and labile food and prefer relatively
      oligotrophic settings. Some deep infaunal species can tolerate anoxia and are
      closely linked to redox fronts within the sediment; they consume more refractory
      organic matter, and flourish in relatively eutrophic environments. Food and
      oxygen availability are also key factors at large (i.e. regional) spatial scales.
      Organic flux to the sea floor, and its seasonality, strongly influences faunal
      densities, species compositions and diversity parameters. Species tend to be
      associated with higher or lower flux rates and the annual flux range of 2-3 g
      Corg m-2 appears to mark an important faunal boundary. The oxygen requirements of
      benthic foraminifera are not well understood. It has been proposed that species
      distributions reflect oxygen concentrations up to fairly high values (3 ml l-1 or
      more). Other evidence suggests that oxygen only begins to affect community
      parameters at concentrations < 0.5 ml l-1. Different species clearly have
      different thresholds, however, creating species successions along oxygen
      gradients. Other factors such as sediment type, hydrostatic pressure and
      attributes of bottom-water masses (particularly carbonate undersaturation and
      current flow) influence foraminiferal distributions, particularly on continental
      margins where strong seafloor environmental gradients exist. Epifaunal species
      living on elevated substrata are directly exposed to bottom-water masses and
      flourish where suspended food particles are advected by strong currents.
      Biological interactions, e.g. predation and competition, must also play a role,
      although this is poorly understood and difficult to quantify. Despite often clear
      qualitative links between environmental and faunal parameters, the development of
      quantitative foraminiferal proxies remains problematic. Many of these
      difficulties arise because species can tolerate a wide range of non-optimal
      conditions and do not exhibit simple relationships with particular parameters.
      Some progress has been made, however, in formulating proxies for organic fluxes
      and bottom-water oxygenation. Flux proxies are based on the Benthic Foraminiferal
      Accumulation Rate and multivariate analyses of species data. Oxygen proxies
      utilise the relative proportions of epifaunal (oxyphilic) and deep infaunal (low
      oxygen tolerant) species. Yet many problems remain, particularly those concerning
      the calibration of proxies, the closely interwoven effects of oxygen and food
      availability, and the relationship between living assemblages and those preserved
      in the permanent sediment record.

PMID- 14601412
TI  - Breeding biology of the intertidal sand crab, Emerita (Decapoda: Anomura).
AB  - Emerita is a burrowing mole crab or sand crab, adapted to life in wave-washed
      sandy beaches of temperate and tropical seas. The reproductive biology of this
      anomuran crab presents several peculiarities, all contributing to its adaptation
      to this harsh environmental niche. We discuss the following aspects: 1) sex ratio
      and size at sexual maturity, 2) neoteny and protandric hermaphroditism, 3) mating
      behaviour and sperm transfer strategy, 4) synchronisation of moulting and
      reproduction, 5) environmental impact on reproductive cycle and egg production,
      6) biochemistry of yolk utilisation and energetics, 7) larval development,
      dispersal and settlement and 8) the value of Emerita as indicator species. These
      aspects are discussed in the light of the life history pattern, comprising a
      sedentary adult and pelagic larval phases. The successful colonisation of the
      physically challenging habitat of the sandy beach by Emerita is attributable
      largely to reproductive strategy and the larval developmental and recruitment
      pattern. Sensitivity to changing environmental conditions, including pollution,
      make this intertidal crab an indicator species for monitoring anthropogenic
      impact.

PMID- 14601413
TI  - Coral bleaching--capacity for acclimatization and adaptation.
AB  - Coral bleaching, i.e., loss of most of the symbiotic zooxanthellae normally found
      within coral tissue, has occurred with increasing frequency on coral reefs
      throughout the world in the last 20 years, mostly during periods of El Nino
      Southern Oscillation (ENSO). Experiments and observations indicate that coral
      bleaching results primarily from elevated seawater temperatures under high light
      conditions, which increases rates of biochemical reactions associated with
      zooxanthellar photosynthesis, producing toxic forms of oxygen that interfere with
      cellular processes. Published projections of a baseline of increasing ocean
      temperature resulting from global warming have suggested that annual temperature
      maxima within 30 years may be at levels that will cause frequent coral bleaching
      and widespread mortality leading to decline of corals as dominant organisms on
      reefs. However, these projections have not considered the high variability in
      bleaching response that occurs among corals both within and among species. There
      is information that corals and their symbionts may be capable of acclimatization
      and selective adaptation to elevated temperatures that have already resulted in
      bleaching resistant coral populations, both locally and regionally, in various
      areas of the world. There are possible mechanisms that might provide resistance
      and protection to increased temperature and light. These include inducible heat
      shock proteins that act in refolding denatured cellular and structural proteins,
      production of oxidative enzymes that inactivate harmful oxygen radicals,
      fluorescent coral pigments that both reflect and dissipate light energy, and
      phenotypic adaptations of zooxanthellae and adaptive shifts in their populations
      at higher temperatures. Such mechanisms, when considered in conjunction with
      experimental and observational evidence for coral recovery in areas that have
      undergone coral bleaching, suggest an as yet undefined capacity in corals and
      zooxanthellae to adapt to conditions that have induced coral bleaching. Clearly,
      there are limits to acclimatory processes that can counter coral bleaching
      resulting from elevated sea temperatures, but scientific models will not
      accurately predict the fate of reef corals until we have a better understanding
      of coral-algal acclimatization/adaptation potential. Research is particularly
      needed with respect to the molecular and physiological mechanisms that promote
      thermal tolerance in corals and zooxanthellae and identification of genetic
      characteristics responsible for the variety of responses that occur in a coral
      bleaching event. Only then will we have some idea of the nature of likely
      responses, the timescales involved and the role of 'experience' in modifying
      bleaching impact.

PMID- 14601414
TI  - Fatty acid trophic markers in the pelagic marine environment.
AB  - Fatty acids have been used as qualitative markers to trace or confirm predator
      prey relationships in the marine environment for more than thirty years. More
      recently, they have also been used to identify key processes impacting the
      dynamics of some of the world's major ecosystems. The fatty acid trophic marker
      (FATM) concept is based on the observation that marine primary producers lay down
      certain fatty acid patterns that may be transferred conservatively to, and hence
      can be recognized in, primary consumers. To identify these fatty acid patterns
      the literature was surveyed and a partial least squares (PLS) regression analysis
      of the data was performed, validating the specificity of particular microalgal
      FATM. Microalgal group specific FATM have been traced in various primary
      consumers, particularly in herbivorous calanoid copepods, which accumulate large
      lipid reserves, and which dominate the zooplankton biomass in high latitude
      ecosystems. At higher trophic levels these markers of herbivory are obscured as
      the degree of carnivory increases, and as the fatty acids originate from a
      variety of dietary sources. Such differences are highlighted in a PLS regression
      analysis of fatty acid and fatty alcohol compositional data (the components of
      wax esters accumulated by many marine organisms) of key Arctic and Antarctic
      herbivorous, omnivorous and carnivorous copepod species. The analysis emphasizes
      how calanoid copepods separate from other copepods not only by their content of
      microalgal group specific FATM, but also by their large content of long-chain
      monounsaturated fatty acids and alcohols. These monounsaturates have been used to
      trace and resolve food web relationships in, for example, hyperiid amphipods,
      euphausiids and fish, which may consume large numbers of calanoid copepods.
      Results like these are extremely valuable for enabling the discrimination of
      specific prey species utilized by higher trophic level omnivores and carnivores
      without the employment of invasive techniques, and thereby for identifying the
      sources of energetic reserves. A conceptual model of the spatial and temporal
      dominance of group-specific primary producers, and hence the basic fatty acid
      patterns available to higher trophic levels is presented. The model is based on
      stratification, which acts on phytoplankton group dominance through the
      availability of light and nutrients. It predicts the seasonal and ecosystem
      specific contribution of diatom and flagellate/microbial loop FATM to food webs
      as a function of water column stability. Future prospects for the application of
      FATM in resolving dynamic ecosystem processes are assessed.

PMID- 14601415
TI  - Mental health care in North Carolina: challenges on the road to reform.

PMID- 14601416
TI  - The North Carolina vision for mental health system reform: people, communities,
      and outcomes.

PMID- 14601417
TI  - Achieving mental health reform: a legislator's perspective.

PMID- 14601418
TI  - Mental health reform: where are we three years later?

PMID- 14601419
TI  - The consumer and family perspective on mental health system reform.

PMID- 14601420
TI  - Terms of engagement: implementing a change process at the local level.

PMID- 14601421
TI  - Living the reform for twenty-five years.

PMID- 14601423
TI  - Illustrating local community initiative in mental health reform: the management
      and treatment of depression by primary care physicians.

PMID- 14601422
TI  - Where they gonna live? Affordability and availability of housing for consumers of
      community based mental health services after reform.
AB  - To successfully meet the needs of persons disabled by mental illness,
      developmental disabilities or substance abuse in a re-organized, de-centralized,
      community-based setting, existing resources dedicated to affordable housing will
      need to be re-targeted and new resources from within the mental health funding
      stream will need to be re-directed to increasing both availability and
      affordability. The gap between the cost of basic housing and what is affordable
      to persons whose resources are limited by their disability is not currently being
      met. Mental health reorganization must address the affordability and availability
      of housing for persons that the system is intending to serve if the entire effort
      aimed at more effective, efficient and economic delivery of mental health
      services is to be successful.

PMID- 14601424
TI  - Workforce demands of mental health reform.

PMID- 14601425
TI  - North Carolina's community hospitals and mental health reform.

PMID- 14601426
TI  - A parents' tale.

PMID- 14601427
TI  - Medical malpractice.

PMID- 14601428
TI  - Medical malpractice.

PMID- 14601429
TI  - Medical malpractice.

PMID- 14601430
TI  - Medical malpractice.

PMID- 14601431
TI  - Medical malpractice.

PMID- 14601432
TI  - Medical malpractice.

PMID- 14601433
TI  - Lessons learned in Lhasa: preserving our trauma centers.

PMID- 14601434
TI  - Good trauma care is no accident.

PMID- 14601435
TI  - The nursing shortage: a time to look at real solutions--STAT!

PMID- 14601436
TI  - Women in medicine--2003 let's celebrate the differences.

PMID- 14601437
TI  - Training tomorrow's physicians in today's environment.

PMID- 14601438
TI  - Philanthropy and its importance to a public medical school.

PMID- 14601439
TI  - Asset protection planning--simple answers to a complex problem.

PMID- 14601440
TI  - Who will take responsibility for America's medical future if we don't? Trial
      lawyers?

PMID- 14601441
TI  - Are trauma centers important? You bet your life!
AB  - Trauma centers and trauma systems are vital community assets. By aggregating
      resources and personnel dedicated to the care of the injured patient, they lower
      trauma morbidity and mortality. The trauma center is a key educational component
      of all members of the health care team. Complex and advanced medical care is
      coordinated in a fiscally responsible manner that facilitates and improves
      patient care and stimulates innovation. The threat of more domestic terrorism and
      mass casualties in the post 9-11 world has exponentially increased the need for,
      and responsibilities of, trauma systems. Healthy trauma centers are an
      indispensable component of a healthy community.

PMID- 14601442
TI  - The challenges of trauma care in the rural setting.
AB  - Trauma occurring in the rural setting presents a unique set of challenges not
      found in more populated areas. Risk of death is distinctly increased, probably as
      a result of prehospital factors such as delayed recognition and inconsistency of
      EMS response and care. Lack of trauma trained physicians and hospital resources
      also contribute to a higher death rate. Development and designation of rural
      trauma centers can be instrumental in reversing this trend. The education in
      trauma care that goes hand-in-hand with designation is probably most responsible
      for better outcomes of trauma patients. The guiding philosophy in such a system
      should be one of 'minimal acceptable care' with early recognition of major trauma
      and expeditious transfer of these patients. This does not obviate the
      responsibility of rural trauma centers to deal quickly and effectively with
      patients in whom ongoing blood loss is an immediate threat to life and to exert a
      damage control approach as an initial phase of treatment.

PMID- 14601443
TI  - Trauma in the elderly.
AB  - As technology and medical care improve, older patients will be more active and
      productive at later ages. Falls and motor vehicle crashes will remain major
      mechanisms of injury in the elderly. Treatment of the elderly trauma patient must
      focus on their complex acute medical needs, their rehabilitation and social needs
      post trauma, and most of all prevention.

PMID- 14601444
TI  - Hemorrahagic shock: a new look at an old problem.
AB  - Shock research during the past 20 years has resulted in advances in our
      understanding of the effects of shock and resuscitation at the cellular,
      molecular, and, increasingly, the genetic level. The authors have measured post
      shock restoration of cellular energy stores as an indicator of cellular recovery
      from shock, and cellular apoptosis as an indicator of tissue damage. Using these
      assessment tools, we have searched for pharmacologic agents that can be used as
      adjuncts to fluid and blood resuscitation to reduce cellular damage and--we hope-
      improve survival. Promising results have been obtained from two quite distinct
      molecular species, specifically crocetin and glutamine. Both of these agents,
      when given during resuscitation, significantly improve restoration of cellular
      energy stores, reduce apoptotic cell death and, at least in the case of crocetin,
      improve overall survival.

PMID- 14601445
TI  - Pathogenesis of sepsis: current concepts and emerging therapies.
AB  - The treatment of sepsis and septic shock is an important clinical problem. While
      effective antibiotic intervention and strong supportive care have improved
      survival, mortality remains at unacceptable levels. The induction of systemic
      inflammation appears to be clearly mediated through a variety of microbial
      products, not all of which have uniform ability to induce gene expression in host
      inflammatory mediator cells. The available evidence would support the conclusion
      that microbial mediators can function synergistically in the induction of host
      inflammation, providing a potential explanation that anti-endotoxin and anti
      inflammatory agents have not been particularly successful in clinical trials to
      treat septic shock. The identification of specific recognition molecules on the
      surface of inflammatory mediator cells responsible for initiation of signal
      transduction, as well as the elucidation of the specific molecular pathways
      leading to gene expression, provide new opportunities for the development of
      effective intervention strategies for treatment of septic shock.

PMID- 14601446
TI  - Transfusion medicine--2003: a comprehensive review, Part II.

PMID- 14601447
TI  - Retroperitoneal haematoma and related organ injury--management approach.
AB  - Retroperitoneal haematoma following blunt or penetrating trauma may arise from
      injuries to bone, major vascular structures, hollow viscera or solid organs.
      Clinical significance varies from inconsequential to fatal. Although the
      guidelines for exploration are clear-cut during laparotomy for associated intra
      abdominal injuries, this is not the case with isolated retroperitoneal haematoma.
      Lateral and pelvic haematomas may be selectively explored and central haematomas
      always need exploration. All penetrating wound tracts should be explored,
      irrespective of the site of the haematoma, to exclude vital structural injury.

PMID- 14601448
TI  - Ischaemic change of the human intestine after total portal occlusion during liver
      resection.
AB  - This is a clinical study of the use of several monitoring techniques to evaluate
      the effect of total hepatic inflow occlusion on intestinal ischaemia during liver
      resection. A total of 8 patients was studied. Parameters measured included
      intestinal oxygen extraction ratio, portal venous and arterial lactate levels and
      intestinal intramucosal pH (pHi), measured by an intraluminal tonometer. When
      venous outflow of the intestine was occluded, intestinal oxygen extraction ratio
      increased and portal venous lactate increased significantly, but arterial lactate
      did not increase significantly until after 60 minutes of occlusion. Intestinal
      pHi decreased significantly after 60 minutes. Following release of the occlusion,
      oxygen extraction and pHi returned to normal in 7 out of 8 patients. The 1
      patient who had a persistent decrease in pHi died postoperatively. These findings
      indicate that a marked drop in pHi after total portal occlusion and persistent
      low pHi following the release of a portal occlusion are associated with the
      development of complications and mortality during liver resection.

PMID- 14601449
TI  - Significance of the portal vein helix.
AB  - BACKGROUND: The portal venous system plays a major role in a variety of disease
      processes. Although the anatomy, histology and physiology of the portal vein have
      been extensively studied over the last century, very little attention has been
      given to its unique helical structure. Previous documentation of the helical
      structure has been based on microscopic, macroscopic and radiological
      appearances. MATERIALS AND METHODS: A more refined method than the above was used
      to image the portal vein helix. Resin casts of the portal venous system were
      performed in 6 rats, 1 baboon and 1 human. RESULTS: All species had a clearly
      demonstrated helical structure of the portal vein situated above the splenic
      vein. CONCLUSION: The unique structure of the portal vein and its subsequent
      helical flow has been neglected in medical research. The significance of the
      activated portal helix and its effect on the blood flow into the liver needs
      further investigation.

PMID- 14601450
TI  - Traumatic rupture of the thyroid gland--a case report.
AB  - Traumatic rupture of the thyroid gland is a rare event. This report describes
      such an injury, in this case caused by a kick from a horse. Blunt injury to the
      anterior structures of the neck involving the major blood vessels and larynx has
      been described, but major blunt injury to the thyroid gland is rare.

PMID- 14601451
TI  - Pathobiology of sacrococcygeal teratomas.
AB  - Sacrococcygeal teratomas are rare tumours, occurring in approximately 1 in 40,000
      live births. The sacrococcygeal area is, however, the commonest site for
      teratomas that are present at birth. There are many conflicting theories as to
      the origin of sacrococcygeal teratomas. Recent studies have begun to shed light
      on some of the dilemmas posed by these enigmatic tumours and have revealed
      factors that impact on therapy and outcome. Advances contributing to the
      understanding of sacrococcygeal teratomas and their impact on prognosis and
      therapy are reviewed in this article.

PMID- 14601452
TI  - Prisoners' health: key concerns.

PMID- 14601453
TI  - Relative priorities.

PMID- 14601454
TI  - The concept of risk and older people: implications for practice.

PMID- 14601455
TI  - Nursing older adults with mental health problems: therapeutic interventions-
      Part. 2.

PMID- 14601456
TI  - Rehabilitation and older people.
AB  - The aim of this article is to examine key factors relating to the rehabilitation
      of older people. After reading it you should be able to: understand what is meant
      by the terms 'rehabilitation' and 'intermediate care' describe the role of the
      nurse in the rehabilitation of older people discuss the benefits of team working
      and a goal-planning approach.

PMID- 14601457
TI  - The treatment of cardiovascular disease in older people.

PMID- 14601458
TI  - In my experience.

PMID- 14601460
TI  - The ethics of theatre nurse practice under the microscope.
AB  - Perioperative practice is a multidisciplinary environment. In some theatres,
      student nurse allocations are at last becoming longer, although some theatres
      still only get a brief visit from student nurses who wish to watch an operation
      all the way through. Furthermore, practically all operating departments have
      trainee operating department practitioners (tODPs). Diploma and degree level
      tODPs are now beginning to produce higher academic levels of coursework and many
      warrant recognition. We should remember that these 'learners' are potentially the
      theatre practitioners of the future and we should encourage them, not only within
      the perioperative environment but also towards their academic achievements.
      Qualified nurses and operating department practitioners (ODPs) now have access to
      various multi-disciplinary post-registration/gradate courses, which not only
      build upon theoretical knowledge, but also enhance practical skills. Individuals
      work long and hard to achieve high level academic pieces of coursework.
      Unfortunately after courses finish many assignments are packed away, collect dust
      and get forgotten, instead of the authors being brave enough to submit them for
      consideration for publication. This new series offers all practitioners the
      chance to share with others their work within this speciality. Whether you are a
      nurse or an ODP undertaking, or having recently completed a course, tODP or
      student nurse (but preferably a member of NATN) the possibility to share your
      experiences or coursework with other perioperative practitioners is available to
      you in these articles. It has always been so, but this new series is dedicated to
      you all and to the hard work you put into your coursework.

PMID- 14601461
TI  - Recruitment and retention. The Derby Theatre Project experience.
AB  - The National Theatre Project was set up in March 2001 by the Modernisation Agency
      to improve the patient and carer experience, improve employee satisfaction,
      optimise theatre utilisation and reduce cancelled operations. This is the second
      article in the series where David Ainsworth, manager of a pilot site project in
      Derby, describes issues around the Theatre Project. This month the focus is on
      recruitment, retention and staff morale.

PMID- 14601462
TI  - Healthcare assistants. To scrub or not to scrub?
AB  - The appropriateness of healthcare assistants expanding their role into the domain
      of scrubbing has been a contentious issue for a long time. Whenever the shortage
      of theatre staff becomes a major concern, expanding the role of the healthcare
      assistant into scrubbing is discussed and decided against. Although allowing
      healthcare assistants to scrub is not the sole answer for all theatre's problems,
      Hazel Smith argues that it would ease a difficult situation.

PMID- 14601463
TI  - The journey. From expert to novice and beyond.

PMID- 14601464
TI  - Desert theatre rats.
AB  - We are pleased to bring you this fascinating insight, from three theatre nurses,
      into life in a 200-bedded field hospital in Iraq. In February 2003 NATN members
      Jane Carey-Harris, a major in the Territorial Army, Mandy Coombs, a captain in
      the Territorial Army, and Pauline Neilson, a captain in the regular Army, were
      all called up. They tell us some of their story.

PMID- 14601465
TI  - [Remembrances].

PMID- 14601466
TI  - [Address by the rector of the Pomeranian Medical University for the inaugural
      academic year 2001/2002].

PMID- 14601467
TI  - [Prenatal development of the human humerus in light of anthropometric
      examinations].
AB  - The study was done on 128 humeral bones (76 male and 52 female; 57 right and 71
      left) obtained from 71 fetuses with C-R lengths ranging from 105 to 255 mm.
      Periosteum and perichondrium were exposed prior to radiography of frontal and
      lateral aspects using a Microphocus 401 bone X-ray apparatus. Radiographs were
      digitized with an analogue camera and an A/D converter for transfer to a PC
      computer. Nine measurements were done for each bone. Changes in proportions
      (structure-to-shaft ratios) during development were studied using non-linear
      regression analysis. The number of nutritive vessels in ossifying bone shafts
      were determined and indices were calculated representing sites of penetration
      into the humerus. The mean C-R length of the fetus when the first ossification
      center in the humerus appeared was 20.34 mm (21.75 mm in females and 19.0 mm in
      males corresponding to gestation age of 7 to 8 weeks). The length of the
      ossifying shaft increased proportionally to C-R length. The regression equations
      representing changes in the proportions of the humerus were linear in four cases:
      minimum anterior-posterior shaft size, minimum medial-lateral shaft size, maximum
      anterior-posterior condylus size, width of distal cartilage. The relative
      decrease in the length of the proximal and distal cartilages and their sum was
      regressed to three hyperbolic functions. The absolute length in mm of these
      cartilages increased. This change could be expressed with three exponential
      equations having positive fractional exponents. A single parabolic equation
      described the increase in the absolute and relative length of the distant chondro
      osseous region. Analysis of the number of nutrient vessels, their direction and
      relation to surrounding structures was done in 76 humeral bones. The results are
      presented for pooled bones, as well as arranged by side (39 (51.3%) right, 37
      (48.7%) left) and gender (54 (71%) male, 22 (29%) female). The number of nutrient
      foramina varied from one to three. A single nutrient foramen was found in 50%,
      two were disclosed in 40.85% and three in 9.2% of bones. Furthermore, 70.25% of
      them were located in zone IV on the anteromedial surface and the medial margin,
      10.75% on the anterolateral and 15.7% on the posterior surfaces. The principal
      nutrient foramen contained an artery accompanied by a relatively large vein. As a
      rule, accessory foramina contained veins only, but in rare cases a branch of the
      nutrient artery was also present. All nutrient canals were directed distally. No
      significant differences were disclosed between right and left, male and female
      humeral bones as to indices representing location of the nutrient foramina.

PMID- 14601468
TI  - [Evaluation of fatty acid levels and selected bioelements in femoral bones of
      chicks depending on age].
AB  - The study was done in Starbro chicks aged 1 to 50 days. Two chicks were collected
      every day and the femoral bones were removed. Altogether, 200 bones were studied.
      The material was divided into 5 age groups (I to V). Compact and spongy bone,
      bone marrow and articular cartilage were sampled. Lipids were extracted according
      to Folch et al. Total lipids were measured spectrophotometrically. Gas
      chromatography was used to study the content of individual fatty acids. Calcium
      (Ca), phosphorus (P), magnesium (Mg) and zinc (Zn) levels were determined using
      atomic absorption spectrometry (Philips PU 9100X), while fluorine content was
      studied with gas chromatography. As the distribution of the results deviated from
      normal, non-parametric Kruskal-Wallis and median tests were used. Correlations
      were studied with Spearman's Rs coefficients. Computations were done with
      Statistica 5.0 (StatSoft) software and the level of significance was taken as p <
      0.05. Statistically significant differences in the fatty acid profile (Tab. 1)
      and content of elements (Tab. 2) were found. The content of fatty acids, calcium
      and fluorine correlated with age. Fatty acids with the highest content in bone
      tissues were C18:1, C16:0, C18:2 and C18:0. The highest content of fatty acids
      was found in bone marrow and the lowest in articular cartilage. Several
      correlations were revealed between individual fatty acids and elements (Tab. 3,
      4). The following conclusions were drawn: 1) The fatty acid profile in compact
      and spongy bone, bone marrow and articular cartilage changed according to age of
      chicks; 2) Content of calcium, phosphorus, magnesium, zinc and fluoride
      correlated with age; 3) Oleic (C18:1), palmitic (C16:0), linoleic (C18:2),
      stearic (C18:0) and arachidonic acid (C20:4) accounted for the majority of the
      fatty acid pool; 4) Correlations in the content of fatty acids and elements were
      noted between bone structures. Fatty acids appear to play an important role in
      the metabolism of bone tissues, particularly in mineralization processes.

PMID- 14601469
TI  - [Skin penetration of sulfamethoxazole and trimethoprim after oral
      administration].
AB  - The aim of this study was to determine the penetration of trimethoprim,
      sulphamethoxazole and its main metabolite--N4-acetylsulphamethoxazole into
      cantharidin-induced skin blister fluid following administration of a single oral
      combination dose of 320 mg trimethoprim and 1600 mg sulphamethoxazole. Moreover,
      penetration of the two drugs into skin blister fluid was compared with
      penetration into the theoretical peripheral compartment calculated on the basis
      of plasma levels found. The material consisted of 12 male patients with bacterial
      skin diseases, treated at the Department of Dermatology and Venerology,
      Pomeranian Academy of Medicine in Szczecin. The age of the patients was 19-64
      years (mean 42 +/- 14), weight 61-112 kg (mean 77 +/- 15), height 166-196 cm
      (mean 175 +/- 8). Prior to enrollment, normal function of gastrointestinal tract,
      liver and kidneys, and absence of allergy to the drugs studied was ascertained.
      The susceptibility of pathogens of cotrimoxazole (trimethoprim +
      sulphamethoxazole) was confirmed with bacteriological tests. Skin blisters were
      induced by applying 0.25% cantharidin ointment. Drug concentrations in plasma and
      skin blister fluid were measured with high-performance liquid chromatography.
      Peak concentrations of trimethoprim in plasma and skin blister fluid were 8.5 +/-
      1.1 mumol/L after 3 +/- 1 h and 5.6 +/- 0.8 mumol/L after 7 +/- 2 h,
      respectively. The differences between both compartments as to parameters measured
      were statistically significant. In the theoretical peripheral compartment, peak
      concentration was 5.8 +/- 2.2 mumol/L after 9 +/- 6 h. Half-times of trimethoprim
      in plasma and skin blister fluid were 11.1 +/- 4.5 h and 12.3 +/- 4.9 h,
      respectively, and did not differ significantly. The degree of drug penetration
      into blister fluid defined as the ratio of area under concentration-time curves
      for blister fluid and plasma was 0.94 +/- 0.23. The differences between
      pharmacokinetic parameters of trimethoprim in skin blister fluid and theoretical
      peripheral compartment were not significant. Peak concentrations of
      sulphamethoxazole in plasma and skin blister fluid were 295 +/- 47 mumol/L after
      3 +/- 1 h and 182 +/- 46 mumol/L after 8 +/- 2 h, respectively. The differences
      between both compartments as to parameters measured were statistically
      significant. In the theoretical peripheral compartment, peak concentration was
      239 +/- 58 mumol/L after 7 +/- 4 h. Half-times of sulphamethoxazole in skin
      blister fluid and plasma were 9.7 +/- 3.3 h and 10.0 +/- 1.1 h, respectively and
      did not differ significantly. The drug penetrated into blister fluid to a high
      extent, although less than trimethoprim, the degree of penetration being 0.82 +/-
      0.21. The majority of pharmacokinetic parameters in blister fluid and theoretical
      peripheral compartment did not differ significantly except for time to peak
      concentration. Peak concentration of N4-acetylsulphamethoxazole, the main
      metabolite of sulphamethoxazole, was significantly lower in blister fluid than
      plasma and took longer to achieve. The half-time of the metabolite was
      significantly longer in blister fluid than in plasma, whereas the ratio of area
      under concentration-time curves in these two biological fluids of 0.86 +/- 0.18
      was similar to that of the parent drug. The results show that both trimethoprim
      and sulphamethoxazole administered together penetrate from plasma into skin
      blister fluid to a great extent and achieve concentrations exceeding the MIC for
      susceptible pathogens. This finding confirms the usefulness of this treatment in
      bacterial skin diseases. The cantharidin-induced skin blister is a useful
      technique to determine the penetration into skin of a drug and its metabolite and
      to evaluate pharmacokinetic parameters. In some cases, this test cannot be
      replaced with theoretical calculations based on drug concentrations in blood.

PMID- 14601470
TI  - [Interaction between fluorine and zinc after long-term oral administration into
      the digestive system of rats].
AB  - Drug interactions are the side effect of administration of two or more drugs or a
      drug-food combination. Although some drug interactions are intentional and
      beneficial to the patient, the majority are unintentional and associated with a
      potentially harmful effect. The aim of this study was to search for interactions
      in rats between fluoride and zinc administered orally for 12 weeks and to
      elucidate any potential toxicological and therapeutic consequences. 60 male
      Wistar rats were divided into six groups of ten rats each and exposed to: 1.
      controls (distilled water); 2. sodium fluoride (NaF); 3. low-dose zinc (Zn); 4.
      high-dose zinc; 5. NaF + low-dose Zn; 6. NaF + high-dose Zn. At the end of the
      experiment the content of F- and Zn+ in serum, urine, incisors, femur and
      mandible was measured and densitometry of femoral bones was performed. Serum
      alkaline phosphatase, alanine and aspartate aminotransferase activities, as well
      as bilirubin and creatinine concentrations were determined to confirm non
      toxicity of fluoride dose. Animals receiving NaF only demonstrated higher content
      of fluorine in serum, urine bones and teeth. Zinc concentrations in serum, urine,
      bones and teeth were elevated in rats receiving zinc with or without NaF.
      Fluorine accumulation in bones and teeth was reduced by Zn, but in general the
      effect lacked statistical significance. Zinc slightly reduced the concentrations
      of fluorine in serum and urine. Sodium fluoride slightly reduced the
      concentration of zinc in serum and urine. Bone mineral content (BMC) was
      significantly increased by NaF and was not further increased by co-administration
      of zinc. No changes in serum alkaline phosphatase, alanine and aspartate
      aminotransferase activities, bilirubin and creatinine concentrations were
      detected. In conclusion, simultaneous administration of fluorine and zinc may be
      beneficial for prevention and treatment of pathologic conditions in bones and
      teeth and is not accompanied by an increase in fluorine levels which could be
      responsible for toxicological symptoms.

PMID- 14601471
TI  - [Level of total and ionized magnesium fraction based on biochemical analysis of
      blood and hair and effect of supplemented magnesium (Slow Mag B6) on selected
      parameters in hypertension of patients treated with various groups of drugs].
AB  - The aim of this work was to determine the concentration of total and ionized
      magnesium in hair and blood of patients with primary hypertension and the
      influence of oral magnesium supplementation (Slow-Mag B6) on clinical parameters
      and blood pressure values. 92 patients were recruited from the Family Care Unit,
      Pomeranian Academy of Medicine in Szczecin. Each patient was treated during at
      least 6 months preceding the study with a single antihypertensive agent from one
      of the following groups: ACE inhibitors, beta-receptor inhibitors, Ca channel
      blockers, diuretics. The control group included patients with hypertension not
      treated pharmacologically. Changes in ionized magnesium concentration before and
      after oral magnesium supplementation were studied in relation to total
      cholesterol, triglycerides, and other parameters of importance in hypertension.
      Significantly lower total magnesium concentrations were demonstrated in hair of
      patients receiving ACE inhibitors and diuretics in comparison to controls.
      Ionized magnesium concentrations in serum of hypertensive patients were
      significantly reduced as compared with controls. A highly significant increase in
      these levels was noted after magnesium supplementation. Blood pressure values
      after magnesium supplementation were reduced in the study group by an average of
      15-20 mmHg for systolic and 5-9 mmHg for diastolic blood pressure. Correlations
      between ionized magnesium and triglyceride concentrations in patients treated
      with Ca channel blockers before oral Mg supplementation were found. Patients
      treated with diuretics demonstrated correlations between total magnesium and
      total cholesterol concentrations. Following oral magnesium supplementation with
      Slow-Mag B6 at 320 mg/day, the frequency of complaints reported by patients,
      including irregular heart beat, pricking heart pain, nervousness, sleep
      disorders, irritability/tearfulness was reduced. There was no effect on other
      complaints, such as mental and physical fatigue, constipation/diarrhea, and
      anxiety.

PMID- 14601472
TI  - [Optimalization for preparation and expansion of ex vivo human umbilical blood
      cells for transplantation].
AB  - This work was aimed at finding optimal conditions for isolation and storage of
      hematopoietic cells from umbilical cord blood and checking the usefulness of ex
      vivo expansion in a serum-free medium. Mononuclear cells were isolated either by
      density gradient centrifugation (Ficoll-Histopaque or Gradisol L) or by
      hypoosmotic lysis of erythrocytes and granulocytes in ammonium chloride. Toxicity
      of metabolic dyes (Hoechst 33342, Rhodamine 123, Pyronine Y) used in flow
      cytofluorimetry and the effects of freezing in dry ice or in a mechanical freezer
      with and without a methanol bath were compared. The influence of ex vivo
      expansion of cells in a serum-free medium on their proliferative potential and
      apoptosis was investigated. In comparison with ammonium chloride, density
      gradient centrifugation both in Ficoll-Histopaque and Gradisol L offered superior
      and consistent results as to cell yield, vitality and proliferative potential.
      Hoechst 33342 demonstrated the highest toxicity with CD34+ cells, disqualifying
      this dye for transplantation purposes. Mechanical freezing with prior methanol
      bath was found to be the safest method of storage. The concentration of TGF beta
      released by cells subjected to expansion ex vivo in a serum-free medium was
      markedly elevated and correlated with the percentage of apoptotic cells.
      Furthermore, the proliferative potential of cells deteriorated as a result of
      expansion.

PMID- 14601473
TI  - [Freezing of umbilical blood cells in mechanical freezers (-80 degrees C)].
AB  - Umbilical cord blood (UCB) contains hematopoietic stem cells capable of
      reconstituting hematopoiesis in the recipient. This property has prompted search
      for methods to store such cells in liquid nitrogen (-196 degrees C) and offer
      them for future use in HLA-matched patients. UCB cells are often collected in
      hospitals remote from storage facilities. Immediate freezing is important to
      prevent apoptosis which develops relatively quickly after isolation from cord
      blood. Investigations into the freezing of bone marrow cells have corroborated
      the feasibility of uncontrolled rate freezing and storage of cells in a
      mechanical freezer at -80 degrees C. The aim of the present study was to apply
      this approach to UCB cells and to determine optimal freezing conditions as
      measured by progenitor cell survival. The highest survival rate among UCB cell
      species subjected to mechanical freezing was demonstrated by mononuclear cells
      enriched for the CD34+ subpopulation. The presence of CD34- mononuclear cells
      (monocytes, lymphocytes) and erythrocytes in the cell suspension reduced
      progenitor cell survival and proliferation potential. Moreover, it was found that
      CD34+ cells from UCB can be frozen in an uncontrolled manner. Optimal results
      were achieved with 10% DMSO and 70% serum. The results were unaffected by the
      type of medium used (RPMI, Dulbecco, Iscove). In conclusion, uncontrolled rate
      freezing of UCB cells is an acceptable method prior to transport of the cells in
      dry ice to a central banking station and storage in liquid nitrogen until needed.

PMID- 14601474
TI  - [Evaluation of peribulbar soft tissue reactions to titanium mesh in experimental
      tests in animals].
AB  - Orbital fractures are often accompanied by periosteal rupture and oculomotor
      muscle injury from the orbital fissure (blowout fracture). During reconstruction,
      substitute material (biomaterial) restoring the orbit is placed on a bony shelf
      and brought into direct contact with muscles and indirect contact with the
      eyeball, optic nerve and lacrimal gland. Histological examination of orbital
      tissues following reconstruction with titanium mesh, not possible in humans, can
      be performed in a rat model. In spite of different anatomy, the rats orbit was
      found satisfactory for the purpose of this study. The eyeball is supported by
      oculomotor muscles, lying partly on the malar bone. The aim was to follow the
      reaction of periorbital soft tissues to titanium mesh in a rat model of inferior
      orbital wall injury simulating orbital muscle lesions in man caused by blowout
      fracture. Insertion of titanium mesh directly in contact with muscles reproduced
      the situation in the human orbit. The following soft tissues and organs were
      studied: striated oculomotor muscle (inferior rectus), sclera, choroid, optic
      nerve and lacrimal gland. The results were compared with sham-operated animals
      (titanium mesh not implanted). Two questions were addressed: Is the process of
      healing of orbital muscle injury affected by the titanium mesh? Is there any
      evidence of adverse effect on periorbital soft tissues or eye of titanium wear
      particles produced by contraction of orbital muscles? Buffalo rats of the 38th
      generation and smooth titanium mesh (Ti-6AI-4V alloy) measuring 0.2 x 8 x 8 mm
      were used.

PMID- 14601475
TI  - [Development of parietal bone based on ossification in the fetus].
AB  - Seventy-two parietal bones from human fetuses aged 15 to 29 weeks were studied.
      Three age groups were formed: I--15-19 weeks; II--19-24 weeks, III--25-29 weeks.
      The width and length of each parietal bone was determined. Microradiological
      studies were done with the Unipan 401 X-ray apparatus. Subsequently, pulverized
      bone for biochemical studies was prepared. Calcium, magnesium, zinc and iron
      content was determined using atomic spectrophotometry. Phosphates were measured
      with a colorimetric method and fluorine was assayed using an ion-selective
      electrode. The dimensions of fetal parietal bones changed almost linearly with
      age until the 20th week of life when a deceleration in the growth rate was noted
      (Tables 1, 2, 3, 4). This finding could be useful for estimation of fetal age
      when other methods are unavailable. The parietal bone is formed from one or two
      primary ossification centers lying in the same plane or one above the other
      (Figs. 1, 2, 3). Fusion of primary ossification centers was observed between 15
      and 19 weeks of life (Fig. 3). Trabeculae radiate from the primary ossification
      center to the periphery of the parietal bone and take the form of a "coral reef"
      within the tuber (Figs. 2 and 5). Transverse ossification which was not
      coordinated with the growth of trabeculae from the primary ossification center
      was observed between week 15 and 19 of intrauterine life (Fig. 2). Fusion of
      peripheral trabeculae with those from the ossification center takes place at a
      later stage of osteogenesis (Fig. 4). Parietal bones of 29-week-old fetuses
      consisted of two layers of trabeculae and a distinct tuber, except for the
      sagittal and coronal sutures and the anterior fontanel, where a single layer of
      trabeculae was observed. Trabeculae were well developed and densely packed (Fig.
      5). Analysis of the mineral composition of fetal parietal bones confirmed that
      the major elements are calcium and phosphorus and that their content increases
      with age (Figs. 6 and 7). Fluorine content differed widely and was unrelated to
      age (Fig. 9, Tab. 1). The importance of fluorine in the process of mineralization
      of parietal bones requires further study. Magnesium content increased with age
      (Fig. 8) and did not correlate with calcium or phosphorus. Apparently, these
      elements play different roles in the process of mineralization. The content of
      zinc and iron, two labile components of bone, decreased with age (Figs. 10 and
      11). Some of these changes could have taken place during storage of the bones.

PMID- 14601476
TI  - [Comparative analysis of elastic materials for lining of removable dental
      prosthesis in vitro].
AB  - This work has dealt with the in vitro physicochemical, elastic, and
      microbiological properties of polymer lining materials used in dental
      prosthetics. Representatives of two soft polymer groups were analyzed: Vertex
      Soft NF, a plastified acrylic polymer, and Molloplast B, a silicon elastomer.
      Vertex Rapid Simplified and Triplex--two acrylic polymers routinely used at the
      Department of Prosthetic Dentistry were chosen as representatives of rigid
      acrylic material. The laminar plates of the denture are lined with elastic
      material to reduce wear discomfort and eliminate symptoms associated with
      compression of the oral mucosa by the denture. Wear-dependent deterioration in
      physicochemical, elastic, and microbiological properties presents as prosthetic
      stomatopathies due to the combined action of mechanical lesions, fungal growth,
      and toxicity of components of the denture, necessitating replacement of the
      denture. Samples used in this study were prepared at the Department of Dental
      Prosthetics, Pomeranian Academy of Medicine. The process of polymerization was
      carried out strictly as recommended by the manufacturers. The in vitro analyses
      were done at the Polymer Institute, Technical University of Szczecin, and the
      Department of Microbiology and Immunology, Pomeranian Academy of Medicine. A
      special system was used to reproduce conditions in the oral cavity and study
      their effects on the elastic liners. Samples were placed in the chamber for
      varying periods, depending on the type of test and material. Thermodynamic
      analysis was done to confirm proper polymerization and hardening. Time-dependent
      loss of contact between the elastic liner and rigid denture under tangential
      (shear) and normal (tear) stress applied to the liner-denture interface was
      examined. Resistance was studied using INSTRON model 4206-006 universal testing
      machine. Compressive changes in elastic properties of the soft materials were
      examined by calculating Young's modulus. Changes in viscoelastic properties of
      the materials depending on temperature and frequency were followed using dynamic
      mechanical thermal analysis (DMTA). A precision microbalance from Sartorius (+/-
      0.00001 g) was used to measure time-dependent changes in weight and sorption of
      water. Adhesion of Candida albicans to the rigid and soft acrylic materials was
      determined after incubation for 3, 6 or 24 h at 37 degrees C. The study has shown
      that adhesive strength is much greater for acryl-acryl than acryl-silicon
      interface. Elastic properties of Molloplast B are very stable and superior to
      those of Vertex Soft NF. Time-dependent sorption of water and changes in weight
      have confirmed the stable nature of Molloplast B. Adhesion of Candida albicans to
      Vertex Soft NF was less noticeable.

PMID- 14601477
TI  - [Diagnosis of thrombophilia based on coagulation and genetic studies].
AB  - Venous thromboembolism and associated complications often leading to permanent
      disability or death are an important problem in modern medicine. Congenital or
      acquired disorders of the hemostatic system, such as hypercoagulation or
      thrombophilia, predispose to thrombosis. The aims of the study were as follows:
      1. To assess the prevalence of thrombophilia in venous thromboembolism and in
      healthy subjects by testing resistance to activated protein C and other markers
      of hemostasis; 2. To screen for factor V Leiden with a PCR-based assay; 3. To
      evaluate the usefulness of the adopted analytical approach for the detection of
      thrombophilia in clinical practice. 29 patients (17 females and 12 males) with
      venous thromboembolism and a history of thrombotic episodes before the age of 40,
      either idiopathic or associated with protracted immobilization, pregnancy or
      puerperium, were enrolled in the study. The control group consisted of 25 age
      matched healthy subjects (14 females and 11 males) without any history of
      thrombosis. The following hemostatic parameters were measured: 1. Activated
      protein C resistance (APC-R); 2. Protein C (PC) and antithrombin III (AT III)
      activities; 3. Protein S (PS) activity; 4. Fibrinogen (FB) concentration; 5.
      Euglobin lysis time (ELT); 6. Prothrombin time (PT); 7. Activated partial
      thromboplastin time (APTT). The presence of Leiden mutation was detected by PCR
      amplification and digestion of products with Mnl 1 restrictase. The results were
      tested statistically using: 1. Kolmogorov-Smirnov D test; 2. Student's t-test; 3.
      linear regression analysis; 4. chi 2 test. The following conclusions were drawn:
      1. Prevalence of thrombophilia in patients with venous thromboembolism is 31%, a
      figure consistent with literature data (no signs of thrombophilia were found in
      the control group); 2. Resistance to activated protein C is sufficient proof of
      Leiden mutation provided that APCR index (r) is less than 0.9 (borderline r
      values (0.9-1.1) require further genetic testing). 3. Methods of diagnosis of
      thrombophilia used in this study could be applied in routine clinical practice,
      the most useful ones being resistance to activated protein C, fibrinogen
      concentration and protein S activity. With this approach the detection of higher
      risk of thrombotic-embolic episodes, either acquired or inborn, is possible in
      most cases.

PMID- 14601478
TI  - [Treatment using the Lehman apparatus in patients with malocclusion in light of
      teleradiologic tests and dental arch measurements].
AB  - The aim of this study was to assess the usefulness of Lehman's appliance for the
      management of distocclusion and to establish indications and contraindications to
      its use. The mean duration of treatment was also determined and compared to such
      in similar form of malocclusion treated with other types of functional
      appliances. Linear measurements were performed on dental plaster casts before and
      after treatment. Cephalometric analysis served to establish the mechanism of
      Class II correction (skeletal or dentoalveolar) and to reveal any increase in
      mandibular length caused by Lehman's appliance. The material consisted of thirty
      three Class II patients (18 girls and 15 boys), aged 9 to 15 years, treated
      successfully with Lehman's appliance for distocclusion. Dental plaster casts and
      lateral cephalograms were obtained at the beginning and end of treatment.
      Improvement in occlusal relationship in the molar, canine and incisor segments
      was the result of dental and skeletal changes. Metric analysis of dental casts
      before and after treatment showed that active treatment was associated with an
      increase in transversal dimensions of the upper arch ranging from 1.8 to 2.4 mm.
      Overbite and overjet decreased considerably. Anterior length of upper arch was
      reduced significantly in boys only and was accompanied by distraction and
      transition from a V-shaped to U-shaped type of arch. These changes helped to
      harmonize transversal dental relationship of both arches and improved conditions
      for functional skeletal base adaptation. Treatment with Lehman's appliance
      improved the intermaxillary relationship and led to a decrease in the ANB angle
      attributable to a change in the SNA angle in girls and the SNB angle in boys. The
      mandibular reaction in girls with Class II/2 was interesting: the SNB angle
      increased considerably, indicating "unblocking" of the mandible. Changes in the
      vertical skeletal relationship were limited to a minor reduction in the index.
      Maxillary incisors moved little, but mandibular incisors showed significant
      proclination. The present findings demonstrate an additional increase in total
      mandibular length achieved with Lehman's appliance. This important effect
      contributed to a successful treatment of Class II malocclusion. Nevertheless, it
      should be remembered that this growth process depends on other factors, such as
      age, growth potential, growth pattern, and duration of appliance use. Average
      duration of treatment was 15 +/- 5.2 months in girls and 17.1 +/- 7.1 months in
      boys. In the case of girls, treatment in skeletal Class I was shorter than in
      skeletal Class II; the contrary was true in boys. Duration of treatment was
      shorter in patients with orthognathic type of face, irrespective of gender.
      Patients with deep vertical relationship showed a better prognosis in terms of
      duration and effects of treatment.

PMID- 14601479
TI  - [Use of acid enamel biopsy in examinations of enamel mineral content of permanent
      human teeth with reference to age and environmental conditions].
AB  - Human activity during the last decades has led to changes in the circulation of
      fluorine and other elements in the natural environment. Due to their narrow
      safety margin, environmental levels of fluorine compounds require careful
      monitoring. Studies on contamination with fluorine of the natural environment in
      Szczecin and its surroundings have a long history. Until recently, maximal
      allowable concentrations of this element in air, water and soil have
      substantially been exceeded. Markers reflecting adverse effects of fluorine on
      living organisms and man, among them magnesium deficit, continued to raise
      concern. The aim of this work was to apply a modified method for enamel sampling,
      the acid enamel biopsy, to determine the content of fluorine and magnesium in
      superficial layers of enamel of permanent teeth in 14-year-old children and
      adults residing in Szczecin or Bialystok--two cities differing as to level of
      contamination of the environment with fluorine compounds. Correlations between
      age and content of fluorine and magnesium in superficial layers of permanent
      teeth were studied as well. Altogether, 40 premolars extracted for orthodontic
      reasons in children and for periodontologic or prosthetic reasons in adults were
      sampled and the mineral content in three superficial layers of enamel on the
      buccal surface was determined. Fluorine concentrations were measured with gas
      chromatography, while calcium and magnesium concentrations were determined with
      atomic absorption spectrometry. The mineral content was studied before and after
      removal of calcium fluorine deposits from the surface and pores of the premolars.
      In addition, the thickness and mass of each layer was calculated (Tables 1 and
      2). To sample the layers, perchloric acid was applied three times to the same
      site and the depth of dissolution after each application was measured (Table 3).
      Total fluorine, structural fluorine and calcium fluorine content was measured in
      each layer (Table 4). Magnesium content was determined before and after removal
      of calcium fluorine deposits (Table 5). The highest content of fluorine and
      magnesium was found in the outermost layer of enamel (Figs. 1-4). The content
      decreased with depth demonstrating a logarithmic relationship. The following
      conclusions were drawn: 1. Increased content of fluorine in the natural
      environment is associated with accumulation of this element in superficial layers
      of the enamel of permanent teeth in the form of structural fluorine. This process
      takes place in children and adults alike. 2. The content of fluorine in enamel
      decreases with depth, irrespective of age and contamination level of the
      environment. 3. Increased content of fluorine in enamel of adults, as compared
      with children, appears to be caused by deposits of calcium fluorine. This process
      takes places independently of environmental contamination with fluorine. 4. A
      deficit of magnesium in the enamel was found in children residing in fluorine
      contaminated areas. In adults, magnesium content was not related to the place of
      residence, suggesting a lack of effect of fluorine contamination of the content
      of magnesium in the enamel. 5. The content of magnesium in superficial layers of
      the enamel decreases with depth following a logarithmic curve. This finding was
      independent of the level of contamination with fluorine or age.

PMID- 14601480
TI  - [Evaluation of the usefulness of vascularized bone grafts for surgical
      reconstruction of the face].
AB  - The process of healing of vascularised bone grafts was examined clinically and
      the use of vascularised bone grafts in face reconstruction surgery was assessed
      basing on author's experience with the surgical technique, availability of graft
      recipient and donor sites and final outcome. Patients enrolled in this study were
      treated at the Department of Maxillofacial Surgery, Pomeranian Academy of
      Medicine in Szczecin, for cancer, injuries, developmental anomalies and atrophic
      changes. In each case it was necessary to restore facial bone structures of
      functional and aesthetic importance, including: floor of the orbital cavity,
      alveolar process of maxilla, palate, malar bone and mandible (Tab. 2).
      Reconstruction was done mostly with parietal bone grafts pedicled on temporal
      fascia and muscle, coronoid process of the mandible pedicled on temporal muscle,
      and lower part of the diaphysis of mandible pedicled on masseter and pterygoid
      muscles. In some cases, reconstruction material consisted of a rib on greater
      pectoral muscle, clavicle on sternocleidomastoid muscle and scapular bone crest
      pedicled on trapezius muscle. Free microvascular flaps with some elements of
      fibula and radius were used in two patients for the reconstruction of mandible
      and soft tissues. In total, 41 vascularised grafts were performed in 40 patients.
      Graft healing was examined clinically and usefulness of this technique for face
      reconstruction surgery was assessed basing on author's experience with the
      preparation technique, intraoperative complications and extent of trauma to donor
      sites. The results of healing of specific grafts are enclosed in Table 1. The
      surgical technique for graft preparation and its transfer into the recipient site
      varied from case to case. The most difficult and effortful approach was with free
      bone grafts transferred from remote sites by means of a microsurgical technique
      (group V). Despite the complexity of the reconstruction method, no intraoperative
      complications occurred in the course of preparation of the radial and fibular
      bone grafts. In group IV, the most difficult grafts included those taken from
      ribs, clavicle and scapular bone. Parietal bone grafts were much less troublesome
      (subgroups Ia and Ib) although associated with the largest number of
      intraoperative complications. The easiest preparation method applied to the
      grafting of coronoid process and lower part of the body of mandible (group II and
      III). Clinical evaluation of vascularised bone grafts confirmed without
      reservations the value of this approach in face reconstruction surgery. However,
      the extent to which individual graft types proved to be usable varied. The most
      valuable ones included parietal bone grafts pedicled on temporal muscle and
      fascia used for restoring upper and central facial structures and the coronoid
      process of mandible pedicled on temporal muscle used for reconstructing the floor
      of the orbital cavity and alveolar process of the maxilla. Rib grafts pedicled on
      pectoral muscle were of limited use. The same applies to grafts from the lower
      part of the body of mandible pedicled on masseter and pterygoid muscles
      occasionally used for restoring the mental part of mandible. Grafts from remote
      sites (fibula, radius) should be used only when other reconstruction methods are
      unavailable.

PMID- 14601481
TI  - [Tomographic evaluation of mastication in women with osteoporosis].
AB  - This study was done in 81 women during early physiological menopause divided into
      three groups: I--controls (without densitometric features of osteoporosis, n =
      29); II--osteopenia (n = 27); III--osteoporosis (n = 25). Tomography was done
      with Somatom Plus instrument (Siemens). Hormone levels were measured with
      commercial test kits. The masticatory organ was evaluated using a questionnaire
      based on a WHO study chart from 1986. Mineral density of L1-L5 vertebral bodies
      in groups II and III was reduced in comparison to controls. Furthermore,
      significantly more women from these groups used dental prostheses. Partial
      prostheses of maxilla and mandibula predominated. No statistical differences
      among the groups were found regarding symptoms associated with temporomandibular
      joints or results of periodontologic measurements. The causes of early loss of
      permanent teeth included caries and less frequently, periapical inflammation and
      delayed or ineffective treatment. The results corroborate the hypothesis that
      reduced bone mass of the masticatory organ leads to loss of permanent teeth and
      increases the demand for prosthetic management in menopausal women.

PMID- 14601482
TI  - [Transcapillary filtration of plasma proteins in patients with diabetes type II
      microangiopathy complications].
AB  - This study presents the results of the research on transcapillary filtration of
      plasma proteins in patients with non-insulin dependent diabetes mellitus (NIDDM).
      The aims of the study were as follows: (a) Examination of transcapillary
      filtration of plasma proteins in patients with NIDDM; (b) Search for correlations
      between metabolic status of diabetes, severity of diabetic microangiopathy and
      penetration of individual protein fractions into the blister fluid; (c)
      Examination of the influence of nonenzymatic glycation on albumin fragmentation
      and its transcapillary filtration. It was also decided to check whether changes
      in the blister fluid would appear earlier than fundal fluorescein angiography or
      microalbuminuria, two markers of diabetic microangiopathy. The study enrolled 34
      patients with type II diabetes mellitus, aged 35-78 years, with a mean disease
      duration of 12.5 years (SD = 7.8). The control group included 10 non-diabetic
      volunteers aged 31-76 years. The mean age in both groups did not differ
      significantly. The cantharidin blister method was used to study the permeability
      of capillary vessels. The following laboratory tests were done: concentrations of
      serum urea, creatinine, glucose, fructosamine, glycated hemoglobin, cholesterol,
      and triglycerides. Electrophoretic separation of proteins in plasma and blister
      fluid was performed and the concentration of fructosamine in fluid was measured.
      Routine urinalysis was supplemented with microalbuminuria. The eye fundus was
      inspected and fundal fluorescein angiography was done. The influence of
      nonenzymatic glycation on protein fragmentation and its possible impact on the
      permeability of capillary vessels was determined with in vitro glycation of human
      serum albumin. In patients without diabetic retinopathy the Cb:Cs ratio for beta
      globulin turned out to be significantly lower than in patients with proliferative
      retinopathy. Patients with normoalbuminuria had the Cb:Cs ratio for alpha 2
      globulin significantly lower than patients with urinary albumin concentrations >
      or = 165 mg/L. When the group was divided with regard to serum fructosamine
      concentrations, the subgroup with fructosamine concentrations lower than 3 mmol/L
      revealed a significantly higher Cb:Cs ratio for fructosamine than the subgroup
      with fructosamine > or = 3 mmol/L. Concentrations of total protein, albumin, beta
      globulin and gamma-globulin in blister fluid correlated positively with glycemia
      in the control group. Blister fluid concentration of beta-globulin correlated
      positively with HbAIC concentration. In the study group, total protein content in
      blister fluid correlated negatively with duration of diabetes and level of
      glycosuria. Concentrations of blister fluid alpha 1-globulin and gamma-globulin
      correlated negatively with glycosuria. Concentrations of blister fluid beta
      globulin correlated negatively with duration of diabetes. Electrophoretic
      separation of in vitro SDS glycosylated human serum revealed no additional
      fraction in the incubated samples. Electrophoretic separation of in vitro
      glycosylated albumin disclosed co-migration of albumin monomers incubated for
      varying times with glucose. CONCLUSIONS: 1. Glycation of human serum and albumin
      does not cause fragmentation of the proteins, but decreases transcapillary
      filtration of albumin due to change of molecular electric charge. 2. Patients
      with non-insulin dependent diabetes and microangiopathic complications reveal
      increased transcapillary transport of alpha 2- and beta-globulin in skin. 3.
      Increased permeability of skin capillary vessels for alpha 2- and beta-globulin
      in diabetic microangiopathy reflects an advanced stage of the disease and may
      facilitate progression.

PMID- 14601483
TI  - [Metabolic disturbances and prognosis in ischemic cerebrovascular stroke in
      patients up to 55 years of age].
AB  - This study was done to establish the relationship between disorders of lipid
      metabolism and risk factors of ischemic cerebrovascular stroke, search for
      correlations between disorders of lipid metabolism and severity of ischemic
      stroke, and assess the association between fibrinogen levels in serum and risk
      factors in patients suffering from different types of ischemic stroke.
      Altogether, 117 patients were enrolled, including 76 males and 41 females aged 20
      to 55 years (mean--45.3 years). The patients were divided into three groups
      depending on the dynamics of neurological symptoms: (1) transient ischemic
      attacks (TIA); (2) reversible ischemic neurologic deficit (RIND); (3) completed
      stroke (CS). The diagnosis was based on history-taking, physical examination,
      laboratory tests and neuro-imaging studies. The tests included a complete blood
      count, glucose, glucose tolerance, 24-hour glucose profile, coagulation profile,
      fibrinogen, total cholesterol, triglycerides, HDL and LDL cholesterol fractions,
      and beta-lipoproteins. Blood was collected on the first day of hospitalization
      prior to any medication. An ECG, CT, and Doppler USG of carotid vessels were
      done. Cardiac etiology of stroke was ruled out with Holter ECG and
      echocardiography. The results were subjected to statistical analysis with Yule's
      coefficient for two qualitative variables. Lipid disorders usually co-existed
      with obesity, fat-rich diets and sedentary lifestyle in all ischemic stroke types
      studied. They were accompanied by elevated blood pressures in every type of
      stroke and by diabetes in TIA. Lipid disorders were found to co-exist with other
      risk factors for ischemic stroke predominantly in female patients, while in male
      patients these disorders were an independent risk factor for ischemic stroke. The
      extent of lipid disorders correlated with the severity of ischemic stroke.
      Elevated levels of fibrinogen in serum were detected in female patients in every
      type of stroke. In male patients, elevated fibrinogen was found only in TIA and
      co-existed with high blood pressure, diabetes and obesity.

PMID- 14601484
TI  - [Evaluation of leptin levels in plasma and their reliance on other hormonal
      factors affecting tissue fat levels in people with various levels of endogenous
      cotisol].
AB  - The discovery of leptin (LEP) shed new light on mechanisms regulating body fat
      mass (BFM). In this aspect, interactions between LEP and glucocorticoids at
      hypothalamic level may be of great importance. Factors that influence plasma LEP
      levels have not been fully recognized and available data on LEP levels are often
      inconsistent. The aim of this study was to evaluate absolute and BFM-corrected
      plasma LEP levels and their diurnal variation, as well as to assess the
      relationship between LEP levels, body fat distribution, and hormones influencing
      body fat in subjects with various levels of endogenous cortisol and different
      nutritional status. Group I was composed of 14 women aged 14-58 yrs, BMI of 23.9
      37.1 kg/m2, with hypercortisolism due to ACTH-dependent and ACTH-independent
      Cushing's syndrome (CUS). 17 women with visceral obesity (OTY) and normal or
      disturbed carbohydrate metabolism, i.e. impaired glucose tolerance (IGT) and
      diabetes mellitus (DM), aged 24 do 50 yrs, BMI 30.0-46.1 kg/m2, were included in
      group II. Group III consisted of 14 women with Addison's disease (AD), aged 18 do
      63 yrs, BMI 15.4-31.6 kg/m2. The control group IV (KON) included 17 healthy women
      with normal BMI. BMI, WHR, body composition, and body fat distribution (DEXA
      method) were assessed in all subjects. Basal plasma levels of LEP, beta-endorphin
      (B-EP), cortisol (F), insulin-like growth factor-1 (IGF-1) were measured with RIA
      test kits. Plasma adrenocorticotrophin (ACTH) levels, serum levels of insulin
      (IRI) and growth hormone (GH) were measured with IRMA test kits. Blood glucose
      (G) concentration was determined with an enzymatic method. Adiposity-corrected
      LEP levels were expressed as LEP/BFM and LEP/%BF indices. Fasting insulin
      resistance index (FIRI) was also calculated. Higher BFM and %BF values were found
      in the OTY group as compared with CUS KON and AD groups. BFM distribution did not
      differ in KON and AD groups whereas CUS subjects exhibited a higher accumulation
      of fat in the trunk when compared to OTY subjects. Absolute LEP levels were
      correlated with trunk BF in CUS patients whereas in KON and AD groups these
      levels were correlated only with limb fat. Absolute LEP levels in CUS and OTY
      groups were comparable, whereas LEP/BFM and LEP/%BF indices were higher in the
      CUS group (Table 1) reflecting upregulation of LEP levels (Figs. 1, 2). BFM
      corrected LEP levels were comparable in groups with normal cortisolemia, i.e. in
      OTY and KON groups, whereas in the AD group both absolute and BFM-corrected LEP
      levels were lower than in controls. No correlation was found between plasma
      levels of F and LEP in CUS and AD groups. This correlation was negative in KON
      (Fig. 3) and positive in OTY groups (Fig. 4). Moreover, KON and AD groups
      demonstrated a negative correlation between plasma ACTH and LEP levels. CUS
      patients showed positive, BFM-independent correlations between LEP levels, FIRI
      and G values, and a positive, BFM-dependent correlation between IRI and LEP
      levels. OTY patients exhibited a BFM-dependent positive correlation between FIRI
      and LEP levels. In these and in AD patients, a positive, BFM-independent
      correlation between IRI and LEP levels was found. Moreover, a negative, BFM
      dependent correlation between GH and LEP levels was found in OTY patients. In
      this group, B-EP levels were positively correlated with LEP/BFM and LEP/%BF
      indices (Fig. 5). A negative correlation between LEP levels, LEP/BFM and LEP/%BF
      indices was ascertained in the AD group. In CUS, OTY, and KON groups, but not in
      the AD group, a midnight increase in leptin levels was observed. In conclusion,
      upregulation of leptin levels in relation to body fat in Cushing's syndrome is
      independent of the source of hypercortisolism. Apparently, it results from
      insulin resistance and hyperglycaemia and contributes to coexisting metabolic
      abnormalities. In Addison's disease, downregulation of leptin may reflect an
      adaptation mechanism to cortisol deficiency and result from low insulin and
      extremely high adrenocorticotrophin levels. In women with normal cortisol levels,
      irrespectively of nutritional status; leptin levels reflect body fat content. In
      obese subjects, leptin levels may be influenced by cortisol levels, high levels
      of insulin, IGF-1, and beta-endorphin as well as low levels of growth hormone.
      Disturbed function of hypothalamic-pituitary-adrenal axis (CUS, AD) does not
      directly influence diurnal variation in plasma leptin levels. In Cushing's
      syndrome, visceral fat may be a predominant source of leptin, whereas in women
      with normal or low cortisol levels peripherally accumulated fat may determine
      leptin secretion.

PMID- 14601485
TI  - [Effect of functional capacity, coexisting depression and some socio-demographic
      factors on the quality of life in patients with ischemic cerebrovascular stroke].
AB  - The aim of this work was to assess the influence of functional capacity,
      coexisting depression and socio-demographic factors (age, gender, education
      level, coexisting disease, employment and hobbies prior to stroke) on the quality
      of life (QOL) in patients with ischaemic cerebrovascular stroke. Enrollment
      criteria included consent to participate, age under 70 years, no physical
      disability or psychiatric disease prior to stroke, no cognitive deficit or speech
      disorders preventing active participation in the study. Each patient was seen on
      four occasions: at the day of discharge from hospital, after 3, 6 and 12 months
      from stroke. The first examination prior to discharge included analysis of the
      hospital record, assessment of the neurological status and functional capacity,
      and screening for depression. Subsequent examinations included assessment of
      functional capacity, search for coexisting depression and evaluation of QOL.
      Functional capacity was determined using the Repta 2 scale, depression was
      diagnosed according to ICD 10 criteria and QOL was assessed with the London
      Handicap Scale. A total of 79 patients appeared for all four examinations. The
      results were subjected to statistical analysis. It was found that functional
      capacity and quality of life steadily improve after stroke, particularly during
      the first 6 months. A positive correlation was disclosed between the functional
      capacity and QOL, indicating that the functional capacity exerts an influence on
      QOL. Depression was a frequent finding among patients with ischaemic
      cerebrovascular stroke, exerting a negative effect on QOL. Higher QOL was
      observed among females and younger patients, the role of gender and age being
      most noticeable in the second half of the first year after stroke. Furthermore,
      patients returning to work and having a hobby demonstrate a higher quality of
      life.

PMID- 14601486
TI  - [Long-term evaluation of filling from selected composite materials and their
      effect on tooth pulp].
AB  - The aim of this work was to assess the long-term performance of several composite
      fillings and the reaction of the dental pulp. The study group consisted of 102
      patients treated at the Department of Conservative Dentistry, Pomeranian Academy
      of Medicine, and at the dentistry office of the author. Altogether, 155
      restorations were done with Herculite, Pertac Hybrid, Valux Plus and Heliomolar
      materials. The patients reappeared for follow-up after 1, 3 and 5 years and the
      restorations were examined clinically using the quality criteria of Ryge for
      surface, shape and marginal adherence of the restoration. Marginal shunt was
      studied with extracted teeth and malachite green under conditions resembling
      those of the oral cavity. Electrical excitability of the pulp was determined with
      the Vitality Scanner apparatus. Opinions of the patients were sought with a
      questionnaire. The results were subjected to statistical analysis. No
      statistically significant differences between the composite materials used were
      found on the basis of Ryge's criteria, except for Pertac Hybrid which revealed
      deterioration of surface quality and adherence. Significantly worse marginal
      adherence with all composites was noted for class I defects according to Black.
      Electrical excitability of the dental pulp was uniformly reduced after five years
      from placement of the filling. The reduction was most evident for class I and II
      defects. A minor marginal shunt was found for all composite materials. Most of
      the patients were satisfied with the quality of the fillings.

PMID- 14601487
TI  - [Evaluation of respiratory tract function in healthy women in the last month of
      uncomplicated pregnancy].
AB  - The aim of this work was to examine the function of the respiratory system in
      pregnant women in the last month of non-complicated pregnancy. Spirometry with
      Lungtest 1000 was performed in 31 pregnant women at a mean gestational age of
      37.72 weeks. In 24 of them the test was repeated after delivery (mean time from
      delivery = 39.40 days). The results were compared with a control group of 31
      healthy non-pregnant resident of Szczecin. Prior to spirometry, all women
      underwent a physical examination with measurement of blood pressure, heart rate,
      body weight and height, chest and abdominal circumference, symphysis-fundus
      distance and blood analysis. Dyspneic symptoms characteristic of pregnancy were
      assessed with the St. George Hospital questionnaire. Spirometric parameters were
      recorded during three stages of the examination: 1. Components of vital capacity
      (IRV, ERV, TV, IC), breathing rate and minute ventilation. 2. Forced respiratory
      parameters (FEV0.5, FEV1, FEV1/FVCEX, FEV1/FVCIN, FEV2, FEV3, FVCEX, VPEF, FIV1,
      PIF, MIF50, FVCIN, VPIF, PEF, MEF25, MEF50, MEF75, FEF25/75, FEF75/85,
      MEF25/FVCIN, MEF50/FVCEX, MEF50/FVCIN, MEF75/FVCIN, FET, FET/FIT, FIT, TTOT,
      TMEF25, TMEF50, TMEF75, TPEF, TPIF, TPEF/FET, TPIF/FIT, MTT, AEX). 3. Maximum
      voluntary ventilation, maximum breathing frequency and breathing reserve. The
      results in all groups were compared with reference values. Furthermore,
      comparative analysis was performed in the same women before and after delivery.
      Data from questionnaires were related to results of spirometry. Parametric and
      nonparametric tests were applied. Spearman's rank test was used to study
      relations between respiratory symptoms and spirometric parameters. Most
      spirometric parameters deviated from reference values. Vital capacity was greater
      than expected. FEV0.5, FEV3, FEV1/FVCEX were reduced. FEV1/FVCIN were reduced in
      pregnant women only. Parameters of forced expiratory flow: FEF25/75, FEF75/85,
      MEF25, MEF25/FVCIN, MEF50/FVCEX were lower than expected. Significant difference
      were disclosed for MTT, AEX and MVV. MTT and MVV were increased and AEX was
      reduced. PEF and MEF75 were decreased in pregnant women. Other parameters did not
      differ significantly. Detailed analysis performed in 24 women before and after
      delivery revealed differences in components of vital capacity. Additionally,
      FEV0.5, FEV1/FVCEX, FEF25/75, MEF25, MEF50, MEF25/FVCIN, MEF50/FVCEX were
      increased in pregnancy. Time parameters of forced expiration--FET and TMEF25 were
      shorter. Minute ventilation was increased in pregnancy although the breathing
      rate was decreased. Values of maximum voluntary ventilation and breathing reserve
      were decreased in pregnancy. Correlation analysis revealed that respiratory
      symptoms in pregnant women depended on changes in proportions among static
      components of vital capacity and abnormalities in forced inspiration (FIT,
      TPIF/FIT). Intensity of symptoms was related to increased heart rate and
      diastolic pressure. CONCLUSIONS: 1. Chief spirometric parameters in the examined
      women differed significantly from reference values. Reliable information about
      respiratory function in pregnant women requires comparison of findings during and
      after pregnancy. 2. Vital capacity in the last month of pregnancy did not differ
      from values after delivery and in the control group. Component volumes changed:
      tidal volume was increased, expiratory reserve volume was decreased, inspiratory
      reserve volume remained unchanged. 3. Minute ventilation recorded at rest in
      pregnancy increased despite decreased breathing rate, whereas maximum voluntary
      ventilation was lower than after delivery and in the control group, evidencing
      reduced breathing reserve. 4. Chief forced expiratory parameters remained
      unchanged in pregnancy. Parameters characterizing bronchioles revealed increased
      air flow (bronchodilation). 5. Dyspneic symptoms found in pregnant women
      correlated with changes in vital capacity components. Symptoms depended on the
      mechanics of ventilation and not on the status of bronchi.

PMID- 14601489
TI  - [Pharmacokinetic comparison of propranolol and atenolol in people with primary
      hypertension].
AB  - The influence of primary hyperlipidemia on the pharmacokinetics of lipophilic
      propranolol and hydrophilic atenolol was studied. Thirty patients with
      hypercholesterolemia, hypertriglyceridemia and mixed hyperlipidemia and healthy
      subjects were enrolled. A single dose of 80 mg propranolol or 100 mg atenolol was
      administered orally using a cross-over study design. Pharmacokinetic parameters
      were calculated according to the noncompartmental open model. The results reflect
      the general tendency to altered pharmacokinetics of lipophilic and hydrophilic
      drugs in patients with disorders of lipid metabolism. In the case of lipophilic
      propranolol, the most pronounced changes were observed in mixed hyperlipidemia,
      with a tendency to reduced steady state distribution volume, decrease in the
      elimination rate constant and total body clearance. In conclusion, the present
      study revealed an influence of lipid disorders on the pharmacokinetics of beta
      blockers, with the most significant alterations seen in mixed hyperlipidemia. The
      dosage of beta-blockers should be modified in patients with an abnormal lipid
      profile in serum.

PMID- 14601488
TI  - [Leptin and it's potential role in the pathomechanism of some hormonal and
      metabolic disorders of patients with anorexia nervosa].
AB  - The obese gene product--leptin (LEP)--is a hormone released from adipose tissue
      implicated in the regulation of nutritional state and energy balance. The aim of
      this study was to assess the relationship between plasma LEP levels and
      nutritional state, secretion of hormones of the hypothalamic-pituitary axis, and
      personality traits in patients with anorexia nervosa (AN). The study was
      performed in 22 women with AN aged 19.45 +/- 0.92 yrs, mean BMI of 15.48 +/- 0.29
      kg/m2, 14 healthy women with normal body weight (NW), aged 29.71 +/- 2.4 yrs,
      mean BMI of 21.22 +/- 0.43 kg/m2, and 19 obese women without metabolic disorders
      (OTY), aged 34.5 +/- 2.65 yrs, mean BMI of 37.47 +/- 2.06 kg/m2. Hormone levels
      were measured with RIA test kits. Psychological examination was carried out by
      means of Gough-Helibrun's and Catell's personality tests. Body mass index (BMI)
      and body composition, i.e. body fat mass (BF) and body fat percentage (%BF) were
      determined with a DEXA instrument (Lunar Co., WI, USA). Absolute plasma LEP
      levels and the LEP/%BF index were lowest in patients with AN whereas LEP/BF index
      did not differ among AN, NW, and OTY groups (Table 1). In all groups, LEP levels
      were positively correlated with BMI, BF, and %BF (Table 2). Plasma neuropeptide Y
      (NPY), beta-endorphin (B-EP), and galanin (GAL) levels in AN were significantly
      higher than in NW and OTY groups (Table 3). Plasma GAL levels were positively
      correlated with LEP/BF and LEP/%BF in AN patients only. Moreover in the AN group,
      serum/plasma levels of insulin (I), insulin-like growth hormone-1 (IGF-1),
      luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol (E2), and
      free triiodothyronine (fT3) were significantly lower, and levels of cortisol (F)
      significantly higher than in NW and OTY groups (Table 4). Plasma LEP levels in AN
      patients were positively correlated with IRI, IGF-1, free thyroxine (fT4), and
      FSH levels, and negatively correlated with thyrotrophin (TSH) levels. Personality
      traits in patients with AN were significantly correlated with hormone levels
      (Tables 5 and 6), BMI and body fat content (Table 6). CONCLUSIONS: 1) Leptin
      secretion from adipose tissue is not related to the nutritional state. 2) High
      levels of NPY, beta-EP, and GAL in AN confirm that starvation is deliberate in
      these patients. Low LEP levels in AN may lead to secondary amenorrhea and thyroid
      function disorders, as well as enhanced cortisol and growth hormone secretion of
      hypothalamic origin. A positive correlation between levels of LEP and IGF-1 and
      IRI may reflect mechanisms preserving adipose tissue and protecting from
      hypoglycemia and insulin resistance. A positive correlation between LEP and fT4
      levels suggests a tendency to energy-sparing under conditions of low energy
      intake. Lack of correlation between LEP and F levels apparently reflects
      peripheral cortisol resistance in AN. 3) Both undernutrition and abnormal hormone
      secretion (LEP, F, fT3, IGF-1, LH, E2) are related to social self-withdrawal,
      defensive attitudes, low self-esteem and high level of self-supervision in AN.

PMID- 14601490
TI  - [Analysis of the value of API and gum bleeding SBI markers for hygiene status in
      adolescent patients using an individual prophylaxis program].
AB  - The purpose of this study was to determine the influence of factors such as age,
      gender, standard of living and prophylactic methods used on API and SBI indices.
      An individual prevention program was started in 182 children aged 6-18 years and
      included 5 visits during 3 years of follow-up. The children were grouped
      according to age as follows: group I (6-9 years; n = 67); group II (10-12 years;
      n = 51); group III (13-15 years; n = 35); group IV (16-18 years; n = 29). During
      each visit the number of caries cavities, results of color test, SBI and API
      values were recorded. Questionnaires were used to determine oral hygiene and
      nutrition habits, as well as the standard of living. A tendency to decreasing SBI
      and API values was noted during the follow-up period, most notable in groups II
      and III (Table 1). Higher SBI and API values were found in boys than girls of
      groups II, III and IV (Table 2). Correlation between API and SBI was ascertained
      in all groups, corroborating the link between parodontitis and oral hygiene. No
      correlation was noted between API and number of cavities (Table 2). Fluoride
      prevention was generally associated with lower SBI and API values. Higher
      standard of living was linked with significantly lower API and smaller number of
      cavities in all age groups (Table 3). According to the questionnaires, dental
      care in terms of regular visits to the dentist, fluoridation and sealing is
      better in children with a higher living standard. Furthermore, these children eat
      less sweats and start toothbrushing earlier in life.

PMID- 14601491
TI  - [Occurrence of genomic species of Borrelia burgdorferi sensu lato in populations
      of Ixodes ricinus ticks from West Pomerania].
AB  - The aim of this study was to determine the incidence of Borrelia burgdorferi
      sensu lato infections in Ixodes ricinus ticks from recreational areas of the
      province of West Pomerania. Ticks (nymphs and adults) were collected between
      April and October 2000 and 2001 from 10 sampling sites. The presence of the
      spirochete, Borrelia burgdorferi sensu lato, was confirmed with an indirect
      fluorescence assay (IFA) and the polymerase chain reaction (PCR). In addition, a
      nested PCR technique was used to detect one of three genomic species of the
      bacteria (B. burgdorferi sensu stricto, B. garinii, B. afzelii). A total of 2380
      ticks were studied, including 2195 nymphs, 89 females and 96 males. Peak
      collection was in June of 2000 (330 ticks) and in August of 2001 (156 ticks)
      (Table 4). Collection was lowest in October of 2000 (93 ticks) and 2001 (127
      ticks) (Tables 2 and 4). The mean infection frequency of Ixodes ricinus as
      determined with PCR was 12.8% in 2000 and 10.9% in 2001. The frequency determined
      with IFA was 11.6% (2000) and 9.6% (2001) (Tables 1 and 3, Figs. 1 and 2). The
      nested PCR technique revealed that the dominant genospecies was B. burgdorferi
      sensu stricto (83.5% of ticks in 2000 and 87.7% in 2001), followed by B. garinii
      (12% and 10.2% in 2000 and 2001, respectively). B. afzelii was detected in 4.4%
      (2000) and 2% (2001) of ticks. Co-infection with B. burgdorferi sensu stricto and
      B. garinii occurred in 3.4% (2000) and 1.8% of ticks (2001). Determination of the
      genomic species was not possible in approximately 7% of ticks (Tables 5 and 6).
      The present results show that there is a substantial risk of contacting
      borreliosis in recreational areas in the vicinity of Szczecin.

PMID- 14601492
TI  - Refusing to settle for less.

PMID- 14601493
TI  - Comprehensive continence care. The nurse practitioner's role.

PMID- 14601494
TI  - Patient information. Iron deficiency anemia.

PMID- 14601495
TI  - Genetic risk assessment for breast and ovarian cancer.

PMID- 14601496
TI  - Hormone therapy today.

PMID- 14601497
TI  - Memories I carry with me.

PMID- 14601498
TI  - Interstitial cystitis.

PMID- 14601499
TI  - Parenting a child with special needs.

PMID- 14601500
TI  - Where are we going? And why am I in this hand basket?

PMID- 14601501
TI  - Asymptomatic hematuria.

PMID- 14601502
TI  - Miller Fisher syndrome.

PMID- 14601503
TI  - Broken heart.

PMID- 14601504
TI  - Raw deal.

PMID- 14601505
TI  - In for the long haul.

PMID- 14601506
TI  - HSJ interview: Jim Gee. Catch them if he can. Interview by Lyn Whitfield.

PMID- 14601507
TI  - Clinical management where medicine meets management. As good as new.
AB  - Diagnostic and treatment centres are providing a boost to community hospitals
      through improved technology and specialist skills. The first primary care DTC was
      opened by North Hampshire PCT last year. Plans in Bristol include a community DTC
      alongside an independent sector treatment centre and local authority leisure
      facilities.

PMID- 14601508
TI  - Mental health. Stepping stones.
AB  - Following a merger, Stepping Hill Hospital's psychiatric division had a bed
      occupancy of 130 per cent. In the next year, the wards will be converted to 23
      bed single sex units. Staff shortages are thwarting the plans by delaying
      openings.

PMID- 14601509
TI  - HSJ people. Live and learn.

PMID- 14601510
TI  - Finance. Sound as a pound.

PMID- 14601512
TI  - Clinical applications of gene therapy.

PMID- 14601513
TI  - Mutagenesis by retroviral transgene insertion: risk assessment and potential
      alternatives.
AB  - Focus on retroviral gene transfer into hematopoietic cells has previously led to
      a proposed classification of side effects and discussion of issues related to
      combinatorial toxicity (including oncogenicity) of genetic interventions. Recent
      data underline that this discussion has to be broadened to any type of stable
      transfer technology. This review summarizes insights obtained in cell culture and
      animal models that were specifically designed to evaluate side effects of
      transgene insertion and new approaches of insertion site targeting. Ongoing
      research aims to reduce side effects of therapeutic transgene insertion by dose
      optimization and definition of contributing risk factors.

PMID- 14601514
TI  - Cytokine- and chemokine-based gene therapy for cancer.
AB  - Cytokines are protein/glycoprotein messengers of the immune system and have
      distinct autocrine and paracrine functions to modulate immunity. Recombinant
      cytokine proteins have been employed as biological drugs for cancer, viral and
      autoimmune targets. Unfortunately, systemic delivery of pharmacological doses of
      proteins often results in severe side effects and toxicities. As these
      therapeutic proteins tend to have very short half-lives and are complex to
      manufacture and deliver, many investigators are evaluating the genetic delivery
      of cytokine genes. Here, some of the promising cytokines currently under
      investigation for cancer therapies are examined, including interleukin (IL)-2, IL
      4, IL-12, IL-24, interferon (IFN)-alpha, IFN beta, IFN gamma, granulocyte
      monocyte colony-stimulating factor and tumor necrosis factor (TNF)-alpha.
      Chemokines are smaller chemotactic cytokines which induce migration of
      leukocytes, activate inflammatory responses, and are implicated in the regulation
      of tumor development and growth. Chemokines can modulate tumor growth via
      regulation of tumor-associated angiogenesis, by activation of host immunological
      responses or by direct inhibition of tumor cell proliferation. In this review,
      chemokines that have been proposed as antitumor drugs will be discussed,
      including Glu-Leu-Arg (ELR)-negative chemokines such as IP-10, MCP-3, MIG and SDF
      1 alpha from the human CXC and C-C chemokine families.

PMID- 14601515
TI  - The role of gene therapy in combined modality treatment strategies for cancer.
AB  - Multimodality therapy has been widely used in cancer treatment for enhancing
      efficacy, reducing toxicity, and preventing or delaying development of
      resistance. However, as the difference in biochemical signals between normal and
      malignant cells is usually trivial, combinations of conventional therapies often
      cause intolerably high levels of toxicity in most cancer patients. Gene therapy
      uses genetically encoded functions to attack molecular events involved in the
      development and maintenance of malignancies, providing a molecular approach to
      eradicate cancer cells or to protect normal cells from the toxicity of
      conventional therapies. Furthermore, gene therapy can also be used to augment
      biochemical signals required for effective chemotherapy and radiotherapy. Recent
      preclinical studies have shown that synergistic effects can be achieved by
      combining gene therapy and conventional anticancer therapies. Moreover, several
      phase I/II clinical studies have demonstrated that anticancer gene therapy is
      well tolerated and that combining gene therapy with chemotherapy, radiotherapy,
      or both, resulted in enhanced antitumor activity without increased toxicity.
      Favorable clinical responses, including a pathologically complete response, have
      been reported in a subset of patients with advanced disease or with cancers
      resistant to chemotherapy or radiotherapy. Thus, combining gene therapy and
      conventional therapies may provide an improvement in the treatment of cancers,
      especially for those resistant to conventional therapies. This review focuses on
      the most recent achievements in cancer treatment by combining gene therapy with
      conventional therapies.

PMID- 14601516
TI  - Gene therapy for chronic pain.
AB  - The dorsal horn of the spinal cord represents an attractive site for
      interventions designed to treat chronic pain, but it has been difficult to
      identify small molecules that act selectively on pain transmission at the spinal
      level. One approach is the use of viral vector-mediated gene transfer to achieve
      focal production and release of short-lived analgesic peptides. Herpes simplex
      virusbased vectors, expressing proenkephalin delivered by subcutaneous
      inoculation, transduce neurons of the dorsal root ganglion, leading to release of
      enkephalin from nerve terminals in dorsal horn to produce an analgesic effect in
      several models of chronic pain. A clinical trial is set to commence.

PMID- 14601517
TI  - Update on gene therapy for cystic fibrosis.
AB  - Cystic fibrosis (CF) is a monogenic autosomal recessive disease. Although several
      organs are affected, severe lung disease is the cause of most morbidity and
      mortality in CF individuals. The first clinical trials in CF patients were
      carried out in 1993, and to date, 29 trial protocols have been published.
      Although proof-of-principle for gene transfer to the lung has been established,
      efficiency is generally low. Steady progress has been made over the last two
      years and key papers, including recent advances in viral and nonviral gene
      transfer agents, will be reviewed here.

PMID- 14601518
TI  - Inflammatory bowel disorders: gene therapy solutions.
AB  - Current options to treat inflammatory bowel diseases (IBDs) are often associated
      with undesired side effects, have limited therapeutic benefit for many patients
      and do not lead to a complete restoration of the mucosal immune balance. Recent
      research progress in the pathogenesis of IBDs has widely broadened our
      understanding of the complex nature of these immunological disorders and
      identified new potential therapeutic targets. New insights into the molecular
      mechanisms underlying IBDs may now allow the development of new in vivo or ex
      vivo therapeutic gene treatment strategies that alter the biological functions of
      cells in the inflamed gastrointestinal tract. New gene transfer approaches based
      either on blocking pro-inflammatory cytokines or overexpression of anti
      inflammatory cytokines, particularly interleukin-10, showed promising results in
      animal models of IBD. Future studies analyzing the effects of cytokine-targeted
      gene therapy in patients are eagerly awaited.

PMID- 14601519
TI  - Update on gene therapy of inherited immune deficiencies.
AB  - Gene therapy has been under development as a way to correct inborn errors for
      many years. Recently, patients with two forms of inherited severe combined
      immunodeficiency (SCID), adenosine deaminase and X-linked, treated by three
      different clinical investigative teams, have shown significant immune
      reconstitution leading to protective immunity. These advances irrefutably prove
      the concept that hematopoietic progenitor cell gene therapy can ameliorate these
      diseases. However, due to proviral insertional oncogenesis, two individuals in
      one of the X-SCID studies developed T-cell leukemia more than two years after the
      gene transfer. Depending upon the results of long-term follow-up, the successes
      together with the side effects highlight the relative merits of this therapeutic
      approach.

PMID- 14601520
TI  - Update on gene therapy for hemoglobin disorders.
AB  - The hemoglobin disorders of beta-thalassemia and sickle cell disease together
      constitute the most prevalent of human monogenic diseases. Although palliative
      therapies and curative allogeneic stem cell transplantation therapy have been
      developed for these disorders, many patients still suffer significant morbidity
      and early mortality. Therefore, development of alternative treatment based on a
      gene therapy approach continues to be a worthwhile endeavor. Several laboratories
      have recently achieved major progress towards this goal. Using lentiviral vectors
      to obtain high-level expression of relatively complex globin gene cassettes,
      therapeutic correction of several murine models of both beta-thalassemia and
      sickle cell disease has been achieved. These breakthroughs, coupled with recent
      significant developments in the ability to select and expand genetically modified
      stem cells in vivo, have greatly advanced the possibility of gene therapy for the
      hemoglobin disorders in the near future. These advances, together with recent
      information regarding safety issues of retroviral gene transfer, are reviewed
      here.

PMID- 14601521
TI  - AAV-mediated gene therapy for hemophilia.
AB  - Gene therapy for hemophilia has been contemplated since the coagulation Factor
      genes responsible for the disease were cloned 20 years ago. Multiple approaches
      towards the delivery of Factors VIII or IX, the defective genes in the most
      common forms of hemophilia, have resulted in positive results in animals, and
      largely equivocal results in human clinical testing. Use of vectors based on
      adeno-associated virus has led to robust and sustained cures in hemophilic mice
      and dogs, and intriguing preliminary results in small or ongoing clinical trials.
      As more clinical experience is gained, solving delivery issues will be of
      paramount importance and will lead to more clinical success. This success will
      permit hemophilia to be cured following a single injection of the normal gene.

PMID- 14601522
TI  - The use of virus-like particles for gene transfer.
AB  - A major challenge in the field of gene therapy is the development of new
      carrier/delivery systems that lack the disadvantages of current transfer systems.
      In the past, some time has been spent developing such modified or alternative
      vectors. A new candidate is represented by virus-like particles (VLPs). It has
      been shown that recombinant expression of the major structural proteins of many
      viruses leads to the formation of VLPs. Such VLPs exhibit morphology similar to
      the empty capsids of the virus from which they are derived. VLPs are non
      infectious, have a similar tropism to the natural virus, and show comparable
      cellular uptake and intracellular trafficking. Since its discovery, VLP
      technology has gained importance in biomedical research. Although most
      investigations into VLP technology have dealt with vaccine development, some
      research groups have demonstrated that VLPs could also represent a useful gene
      therapy delivery system. This review will focus on studies performed with VLPs
      from members of the Papillomaviridae and Polyomaviridae families.

PMID- 14601523
TI  - Non-primate lentiviral vectors.
AB  - Feline and equine lentivirus-derived vector systems are yielding impressive
      preclinical results in tissue culture, animal and ex vivo human organ models.
      Improved basic scientific understanding of lentiviral life cycles is facilitating
      development of these vectors, and initial systems based on other lentiviruses
      have been constructed. In addition to further engineering of the individual
      platforms for safety and efficacy, important goals for the field are to compare
      different lentiviral vector systems rigorously in specific human targets, and to
      derive clinical grade packaging/producer cell lines. Further progress in
      fundamental virology will be critical. Species-specific lentiviral restriction
      has recently emerged as a dynamic subject relevant to lentiviral pathogenesis
      research and lentiviral vector-based gene therapy. This review summarizes recent
      results in this growing field and discusses elements of an agenda for furthering
      application of these vectors to human gene therapy.

PMID- 14601524
TI  - Technology evaluation: ABX-EGF, Abgenix/Amgen.
AB  - Abgenix and Amgen (formerly Immunex) are developing ABX-EGF, a human monoclonal
      antibody against the epidermal growth factor receptor, for potential use in the
      treatment of cancer. ABX-EGF is undergoing phase II trials in patients with
      renal, colorectal, prostate and non-small-cell lung cancers. By July 2002, phase
      III trials for these indications were planned to start in 2003.

PMID- 14601525
TI  - Technology evaluation: LErafAON, NeoPharm.
AB  - NeoPharm is developing liposome-encapsulated, c-Raf antisense
      oligodeoxynucleotides (LErafAON) for the potential treatment of various solid
      tumors, including those that have become resistant to radiation or chemotherapy.
      Phase I/II trials commenced in March 2001 and were ongoing as of June 2003.

PMID- 14601526
TI  - Technology evaluation: CpG-7909, Coley.
AB  - Coley Pharmaceutical (formerly CpG ImmunoPharmaceuticals) is developing CpG-7909
      (ProMune) for use in the potential treatment of cancer and as a vaccine adjuvant.
      By April 2000, CpG-7909 had entered phase I/II trials for cancer and in March
      2002, Coley initiated a phase I trial in non-Hodgkin's lymphoma in combination
      with rituximab (Rituxan). By October 2002, CpG-7909 was in phase II trials as a
      vaccine adjuvant. Cpg-7909 is currently also undergoing phase II trials for
      melanoma.

PMID- 14601527
TI  - Technology evaluation: R-1549, Antisoma/Roche.
AB  - R-1549 (formerly known as pemtumomab), a murine monoclonal antibody (HMFG1)
      specific for the cancer antigen PEM and radiolabeled with yttrium-90, is under
      development by Antisoma and Roche as a potential treatment for ovarian and
      gastric cancer. In July 2003, enrollment for a phase III trial in ovarian cancer
      was completed.

PMID- 14601528
TI  - Effective strategies to comply with Joint Commission's universal protocol.

PMID- 14601529
TI  - Are you ready for your first unannounced survey?

PMID- 14601530
TI  - Are you complying with CMS' new PI standards?

PMID- 14601531
TI  - Foolproof ways to improve physician handwriting.

PMID- 14601532
TI  - Review resuscitation and outcomes.

PMID- 14601533
TI  - Patient safety offers new opportunities in quality field.

PMID- 14601534
TI  - Politicizing science: the case of the Bush administration's influence on the lead
      advisory panel at the Centers for Disease Control.
AB  - Since the 1970s, the CDC has depended upon independent scientists and policy
      consultants, who are experts in the field to gather information and provide
      advice to the CDC regarding policy initiatives for a variety of toxic materials.
      One of the most important safeguards of the scientific integrity of governmental
      policy and research has been the 258 scientific advisory committees to the
      various branches of the CDC that presently help policymakers decide on the
      appropriate means of addressing serious scientific issues. These advisory
      committees, while not possessing the actual power to reshape policy, are
      important in their role as the font of expert opinion available to various CDC
      chiefs. During the past two years, the Bush administration has sought to short
      circuit the traditional manner in which appointments to the committees have been
      made and to substitute a process that by and large has reflected its own well
      known anti-regulatory and anti-environmental agenda. In this paper we will look
      at this process, focusing on one important committee that has been responsible
      for protecting the nation's children from the devastating effects of lead on
      their neurological well-being.

PMID- 14601535
TI  - Local health departments' mission to the uninsured.
AB  - It is often maintained that local health departments (LHDs) should not directly
      provide personal health services. However, our nationally representative sample
      revealed that most LHD directors (87%) believed LHDs must directly provide these
      services, primarily because they perceived a high level of unmet need among the
      uninsured. While only a minority believed LHDs should focus exclusively on the
      core functions, this proportion rose dramatically when we asked directors to
      assume that there were no uninsured people. Directors who perceived a high level
      of unmet need among the uninsured in their jurisdictions were much less likely to
      believe that LHDs should exclusively focus on the core functions. In theory, LHDs
      have a unique responsibility for assuring that the uninsured and vulnerable have
      access to personal health services. However, a majority of directors (67%)
      acknowledged that they have no enforceable means of assuring access to services
      the health department did not directly provide.

PMID- 14601536
TI  - Coverage of childhood nutrition policies in California newspapers.

PMID- 14601537
TI  - Review of the National HIV/AIDS Control Programme in India with a view to making
      it community-oriented, more effective, and sustainable.

PMID- 14601538
TI  - Nonprofit organizations versus government agencies to reduce tobacco use.
AB  - Tobacco settlement money can be allocated to nonprofit organizations or
      government agencies. Both have advantages and disadvantages. Nonprofit
      organizations may have relatively (a) more efficiency/flexibility, but less
      accountability; (b) narrower focus, but less experience; (c) more ability to
      advocate, but more obligations; (d) more independence from tobacco industry
      influence, but less funding; and, (e) more public trust, but less visibility. The
      present case study of the Partnership for a Healthy Mississippi focuses on six
      interconnected areas: education (school and community), raising awareness,
      advocacy, service, enforcement, and research. In 1999 and 2000, tobacco use
      declined in Mississippi, even compared to neighboring states. This unique
      partnership's multifaceted approach to social change probably facilitated this
      decline.

PMID- 14601539
TI  - Emotions, fertility, and the 1940s woman.
AB  - This paper looks at the ways that women's reproductive issues, particularly
      sterility, were explained during the post-World War II period. In the absence of
      a clear physiological basis, sterility was depicted as a product of
      psychoanalytic causes rooted in women's psychology. When women were yearning for
      a reason for their infertility and desperate for effective treatments, a
      psychoanalytic framework treated deficiencies lurking in the field of
      infertility. Framing infertility within a psychiatric construct influenced how
      women were treated by their medical specialists and how they were perceived by a
      public that expected married women to reproduce. An infertile woman was already
      considered a failure by society. By establishing her illness within the context
      of her own repressed desires, she was no longer an unwitting victim, but a
      culprit.

PMID- 14601540
TI  - A long way to fall.

PMID- 14601541
TI  - Clinical management where medicine meets management. Special needs.
AB  - Independent and innovative GPs are often attracted to a specialism. Specialist
      GPs provide a bridge between primary and secondary care. A formal framework for
      specialist training is now in place.

PMID- 14601542
TI  - Mental health. Block release.
AB  - Staff were demoralised while working at a visibly crumbling former asylum in
      Essex. While awaiting a move to new, purpose-built premises in 2005, the trust
      spent 2 Pounds m on improvements. Work was intended to increase patients' dignity
      and privacy.

PMID- 14601543
TI  - HSJ people. Straight to the point.

PMID- 14601544
TI  - Law. Winners and choosers.

PMID- 14601545
TI  - Palliating advanced pancreatic cancer--in search of the Holy Grail.

PMID- 14601546
TI  - J.H. Louw Memorial Lecture. Liver surgery: 'traveller, there is no path, a path
      is made by walking'.
AB  - Liver resection today is a product of rapid development over the past two
      decades. The description of the functional anatomy of the liver was the
      foundation of modern liver surgery. However, it has been the technological
      advances in radiology that have had the biggest impact in the management of
      hepatobiliary disease. Major hepatectomies dominated the earlier experience of
      modern liver surgery, but segment-orientated resections now play a more prominent
      role. Resections may be performed for both malignant and benign lesions or as an
      emergency procedure for trauma or other catastrophic event. At Princess Alexandra
      Hospital, Brisbane, 1,108 liver resections have been undertaken. Of the elective
      resections, 45% were for metastases, 29% for primary malignancy and 26% for
      benign disease. Two-thirds of the 102 emergency hepatectomies were for severe
      liver trauma. The 30-day mortality was 3.2% for the total series, 2.6% for the
      elective cases and 1.5% for the elective, non-jaundiced patients. Innovative
      graft reduction techniques have become a major component in liver
      transplantation. The successful transplantation of a reduced-size segmental graft
      from an adult donor liver to an infant paved the way for other procedures such as
      split-liver, auxiliary partial orthotopic and living-donor transplantation.

PMID- 14601547
TI  - Clinicopathological features of Meckel's diverticula in 32 patients, with
      emphasis on the presence of Helicobacter pylori.
AB  - Meckel's diverticula (MD) with areas of gastric heterotopia (metaplasia) are more
      likely to become symptomatic than those that contain mucosa of purely an
      intestinal type. Helicobacter pylori has been associated with the pathogenesis of
      various diseases. The aim of the study was to evaluate whether H. pylori could be
      identified within metaplastic gastric mucosa in MD. A retrospective evaluation of
      the histopathological features and the clinical presentation of patients with MD
      was undertaken. The study group included 32 cases (20 paediatric and 12 adults).
      The commonest modes of presentation were acute pain (25%), obstruction (19%),
      bleeding (12.5%) and hernias (9%). On histological examination, heterotopic
      gastric mucosa was noted to be present in 12 cases. Of these, 3 specimens were
      noted to have H. pylori organisms present using a specific immunostaining
      technique. Two patients had concurrent gastric biopsies; one stained positively
      for H. pylori but the second (1 mm biopsy) was rapid urease-test positive only.
      In conclusion, the study provides strong evidence that H. pylori may colonise
      heterotopic gastric mucosa in a minority of MD. H. pylori is apparently not
      involved in the pathogenesis of most cases of complicated MD. Nonetheless, all 3
      patients who had evidence of H. pylori were symptomatic.

PMID- 14601548
TI  - The peritoneo-saphenous shunt for palliation of refractory ascites.
AB  - OBJECTIVE: To describe a safe surgical technique for the management of refractory
      ascites. PATIENTS AND METHOD: Two preterminal patients with respiratory
      compromise caused by refractory ascites had the long saphenous vein transected at
      mid-thigh and anastomosed to the peritoneum in the region of the internal
      inguinal ring. This allowed direct drainage of the ascitic fluid into the
      vascular system (peritoneosaphenous shunt). RESULTS: The procedure was performed
      successfully on two patients. The first patient, with cirrhosis, was leading a
      normal lifestyle without diuretic use at 7 1/2 months' follow-up. The second
      patient, with cirrhosis and multifocal hepatoma, was fit enough for discharge
      without medication. CONCLUSION: The peritoneo-saphenous shunt deserves further
      evaluation as a novel and safe surgical technique for the management of
      refractory ascites.

PMID- 14601549
TI  - Anastomotic aneurysm following aortobifemoral bypass.
AB  - OBJECTIVE: The aim of this study was to establish the incidence of anastomotic
      aneurysm following aortobifemoral bypass and to document management of this
      condition in our practice. DESIGN: This is a prospective study of anastomotic
      aneurysms developing in patients with aortobifemoral bypasses followed up for 49
      months. SETTING: Two tertiary referral hospitals served by the Durban
      Metropolitan Vascular Service. PATIENTS: Four hundred and ninety-two patients
      underwent aortobifemoral bypass. Anastomotic aneurysms (N = 25) developed in 23
      patients. Presence of anastomotic aneurysm was confirmed by Doppler ultrasound.
      INTERVENTIONS: All patients underwent aneurysm repair. RESULTS: Operations
      performed were: excision and interposition graft (15), re-suture (6), tube graft
      (1), crossover (1), graft-popliteal bypass (1) and ligation (1). There were no
      deaths and no recurrences. Wound infections occurred in 2 patients and occlusion
      of the opposite limb occurred in 1. CONCLUSION: Anastomotic aneurysms following
      aortobifemoral bypass are uncommon. They commonly occur as a result of
      anastomotic disruption. Management includes repair or excision, depending on the
      prevailing circumstances, and can be performed with good results.

PMID- 14601550
TI  - Penetrating cardiac injuries--current evaluation and management of the stable
      patient.
AB  - Patients with penetrating cardiac injuries present in a stable or only mildly
      shocked condition--especially if the laceration has sealed off and the patient
      has been adequately resuscitated. A large proportion of patients presenting to
      our unit are in a reasonably stable condition after resuscitation, and rapid
      diagnosis may be difficult. We present our experience over a 5-year period (191
      patients), with particular reference to the stable patient. All patients with
      penetrating precordial wounds should be assessed for a possible cardiac injury,
      especially if a period of hypotension has occurred. Clinical signs, central
      venous pressure, chest radiograph, pericardiocentesis and subxiphoid window are
      not always helpful in the diagnosis. Cardiac ultrasound is very useful (in the
      absence of haemothorax), and was performed in 103 of 191 patients, with 8 false
      negatives and 3 false-positives. When an unstable patient presents with an
      obvious diagnosis use of cardiac ultrasound should be restricted. A subxiphoid
      window has diagnostic value where the cardiac ultrasound is inconclusive.

PMID- 14601551
TI  - Choledochal cyst with perforation--an unusual presentation. Case report and
      review of the literature.
AB  - A unique case of a 22-month-old baby girl with a perforated choledochal cyst, who
      presented with vague abdominal symptoms but without any jaundice, an acute
      abdomen and an incidental finding of acholic stools, is described below with a
      review of the literature.

PMID- 14601552
TI  - Is skull radiography necessary for open scalp wounds in minor head injuries?

PMID- 14601553
TI  - Optimizing efficacy and tolerability in today's HAART.

PMID- 14601554
TI  - Building a better nucleoside/nucleotide analogue backbone: pharmacokinetic and
      resistance considerations.

PMID- 14601555
TI  - Emtricitabine: a new treatment option for simplified antiretroviral therapy.

PMID- 14601556
TI  - Oxidative stress and activation of proteasome protease during serum deprivation
      induced apoptosis in rat hepatoma cells; inhibition of cell death by melatonin.
AB  - Growth factor deprivation-induced apoptosis has been shown in various cell
      systems and is recognized as one of the standard models for the study of
      programmed cell death. The mechanism of induction of apoptosis by serum
      deprivation is still not clear. The objective of the present study was to
      investigate if serum-deprivation causes oxidative stress, which then leads to
      apoptotic death. We have demonstrated that indeed, there was a significant
      increase in reactive oxygen species following serum deprivation of 5123tc
      hepatoma cells. Furthermore, treatment with anti-oxidants; melatonin or vitamin
      E, prevented cell death caused by serum-deprivation. We also demonstrated that
      there was activation of proteasome proteases and decrease in glutathione levels
      following serum deprivation. Interestingly, melatonin treatment blocked these
      changes and rescued the cells from apoptosis induced by serum-deprivation. These
      results indicated that oxidative stress may play a causal role in the induction
      of apoptosis induced by serum deprivation.

PMID- 14601557
TI  - Anti-IgM-induced down-regulation of nuclear Thy28 protein expression in Ramos B
      lymphoma cells.
AB  - We recently cloned mouse Thy28 cDNA (mThy28), which is highly conserved among
      vertebrates and plants. The mThy28 mRNA is highly expressed in testis, liver,
      kidney, brain, with moderate expression in thymus, spleen, and heart. In the
      present study, characteristics of mouse Thy28 protein expression were examined
      using rabbit anti-mThy28 polyclonal antibody (Ab). Levels of mThy28 protein
      expression were highest in testis, with moderate expression in liver, spleen, and
      thymus. The Thy28 protein was mainly located in the nucleus, which was revealed
      by immunofluorescence microscopy and Western blotting using anti-mThy28 Ab, and
      transient expression of the mThy28/EGFP fusion gene. Engagement of membrane
      immunoglobulin with anti-IgM induced down-regulation of human Thy28 expression at
      both mRNA and protein levels, accompanied by induction of apoptosis in Ramos B
      lymphoma cells. Expression of protein and mRNA and induction of apoptosis were
      evaluated by flow cytometry/Western blotting, reverse transcription-polymerase
      chain reaction, and propidium iodide staining, respectively. Anti-IgM also down
      regulated the promoter activity of the mThy28 gene, as demonstrated by luciferase
      assay. Thus, the anti-IgM-induced down-regulation of the nuclear Thy28 expression
      appears to correlate with the induction of apoptosis in Ramos B lymphoma cells.

PMID- 14601559
TI  - A common mechanism for the mechanosensitive regulation of apoptosis in different
      cell types and for different mechanical stimuli.
AB  - In all kinds of tissue cells are influenced by mechanical forces. In vivo
      fibroblasts are exposed to mechanical tension and endothelial cells are subjected
      directly to hemodynamic flow. It has been shown that disturbance of the
      mechanical stimulus leads to apoptosis by induction of an autocrine loop with
      thrombospondin-1 as ligand and an integrin/integrin associated protein (CD47)
      complex as receptor. In the present study the nature of the mechanical stimulus
      has been exchanged for these two cell types. If fibroblasts are subjected to
      laminar flow apoptosis decreases about 20-fold whereas turbulence leads to an
      significant increase compared with the static conditions. If endothelial cells
      grown on thin silicone membranes are exposed to permanent and pulsatile uniaxial
      strain, the cells are completely devoid of apoptosis. The thrombospondin-1
      secretion as well as the expression of CD47 occurs exclusively under mechanical
      relaxation respectively turbulence. So different types of cells seem to share a
      common sense deciding whether a mechanical stimulus induces or suppresses
      apoptosis and use a common molecular machinery for the regulation of the process.

PMID- 14601558
TI  - Cytofluorometric quantitation of apoptosis-driven inner mitochondrial membrane
      permeabilization.
AB  - The mitochondrial matrix can be specifically labeled by loading cells with
      calcein and simultaneous quenching of the non-mitochondrial calcein fluorescence
      with cobalt (Co2+). Positive staining of mitochondria thus requires that the
      inner mitochondrial membrane functions as a barrier separating calcein (within
      the matrix) from Co2+ (outside of the matrix). Upon induction of apoptosis, such
      calcein/Co2+ -labeled cells, demonstrate a decrease in the overall calcein
      fluorescence resulting from inner mitochondrial membrane permeabilization. This
      decrease can be quantified by cytofluorometry and can be dissociated from other
      apoptosis-associated mitochondrial perturbations such as the loss of the
      mitochondrial transmembrane potential (delta phi m), the local overproduction of
      re-active oxygen species, and the mitochondrial release of cytochrome c. In some
      paradigms of apoptosis the loss of calcein/Co2+ (CC) staining can be dissociated
      from the delta phi m loss, both of which may occur in a caspase-dependent or
      caspase-independent fashion, depending on the apoptosis inducer. Importantly,
      inner membrane permeabilization to CC may occur without a permanent delta phi m
      dissipation in apoptosis, suggesting that transient permeabilization events could
      participate at the apoptotic cascade. Altogether, our data demonstrate that inner
      mitochondrial membrane permeabilization constitutes an early event in the
      apoptotic cascade.

PMID- 14601561
TI  - Association of cyclooxygenase-2 expression with prognosis of state T1 grade 3
      bladder cancer.

PMID- 14601560
TI  - Cell death in human acute myelogenous leukemic cells induced by
      pyrrolidinedithiocarbamate.
AB  - Pyrrolidinedithiocarbamate (PDTC) is a metal chelating compound, which exerts
      both pro-apoptotic effect and pro-oxidant activity on many cells. Our objective
      was to investigate whether PDTC was able to interfere with apoptotic process in
      leukemic and normal bone marrow CD34+ cells. Since hematopoietic growth factors
      stimulate growth and differentiation and prevent apoptosis, we therefore studied
      the effect of growth factors pretreatment, such as interleukin-3 and granulocyte
      macrophage colony stimulating factor, in human myeloid CD34+ cells to evaluate
      whether they protect the cells from the apoptotic action of PDTC. We revealed
      that PDTC exerted an apoptotic effect in leukemic CD34+ cells. This effect was
      dependent on the ability of this compound to generate the oxidation of cellular
      glutathion to its disulphide and consequently to induce an intracellular
      oxidative stress. Hematopoietic growth factors did not protect cells from
      apoptosis induced by previous treatment with PDTC. The ability of PDTC to induce
      apoptosis was restricted to acute myelogenous leukaemia CD34+ cells, since normal
      CD34+cells were insensitive to the pro-oxidant effect of PDTC. These findings
      imply that normal cells are equipped with mechanisms by which they respond
      differently to PDTC effects with respect to leukemic cells.

PMID- 14601563
TI  - Microstaging of pT1 transitional cell carcinoma of the bladder. Does it really
      differentiate two populations with different prognoses? (pT1 subcategory).

PMID- 14601562
TI  - Frequent administration of angiogenesis inhibitor TNP-470 (AGM-1470) at an
      optimal biological dose inhibits tumor growth and metastasis of metastatic human
      transitional cell carcinoma in the urinary bladder.

PMID- 14601564
TI  - Intravesical pH: a potentially important variable affecting efficacy and the
      further development of anthracycline chemotherapy for superficial bladder cancer.

PMID- 14601565
TI  - Semen quality of male smokers and nonsmokers in infertile couples.

PMID- 14601566
TI  - Development outcome at 2 years of age for children born after ICSI compared with
      children born after IVF.

PMID- 14601567
TI  - Chromosomal abnormalities in embryos derived from testicular sperm extraction.

PMID- 14601568
TI  - Induction of spermatogenesis in azoospermic men after varicocele repair.

PMID- 14601569
TI  - Use of carnitine therapy in selected cases of male factor infertility: a double
      blind crossover trial.

PMID- 14601570
TI  - Efficacy of sildenafil as adjuvant therapy to selective serotonin reuptake
      inhibitor in alleviating premature ejaculation.

PMID- 14601572
TI  - Prevalence and predictors of sexual dysfunction in patients with type 1 diabetes.

PMID- 14601571
TI  - Sildenafil citrate for treatment of erectile dysfunction in men with type 1
      diabetes. Results of a randomized controlled trial.

PMID- 14601573
TI  - Effects of tadalafil on erectile dysfunction in men with diabetes.

PMID- 14601574
TI  - Antimicrobial activity of antibiotic-soaked, Resist-coated Bioflex.

PMID- 14601575
TI  - Inflatable penile prosthesis: site-specific malfunction analysis.

PMID- 14601576
TI  - Intracavernosal vascular endothelial growth factor (VEGF) injection and adeno
      associated virus-mediated VEGF gene therapy and reverse venogenic erectile
      dysfunction in rats.

PMID- 14601577
TI  - Increased contractility of diabetic rabbit corpora smooth muscle in response to
      endothelin is mediated via Rho-kinase beta.

PMID- 14601578
TI  - Adeno-associated viral gene transfer of dominant negative RhoA enhances erectile
      function in rats.

PMID- 14601579
TI  - Treatment of antidepressant-associated sexual dysfunction with sildenafil: a
      randomized controlled trial.

PMID- 14601580
TI  - Protease and reverse transcriptase mutation patterns in HIV type 1 isolates from
      heavily treated persons: comparison of isolates from Northern California with
      isolates from other regions.
AB  - We compared HIV-1 subtype B reverse transcriptase (RT) and protease mutation
      patterns in isolates from heavily treated persons in Northern California with
      those from persons described in the published literature predominantly from other
      parts of the United States and Europe. There were few differences in the
      prevalence of single, double, and triple mutations between the two sets of
      sequences. More complex patterns of mutations could be characterized by
      clustering the sequences into eight groups of RT sequences and nine groups of
      protease sequences according to the presence of known drug-resistance mutations.
      This clustering accounted for 63% of the variation at RT inhibitor-resistance
      positions and 68% of the variation at protease inhibitor-resistance positions.
      The majority of clusters contained Northern California and literature sequences
      in similar proportions.

PMID- 14601582
TI  - The making of a disease: female sexual dysfunction.

PMID- 14601581
TI  - Sexual disabilities are not singularities.

PMID- 14601583
TI  - High dose sildenafil citrate as a salvage therapy for severe erectile
      dysfunction.

PMID- 14601584
TI  - Proceedings of the 16th Annual Conference on Military Medicine. June 17-20, 2002.
      Bethesda, Maryland, USA.

PMID- 14601585
TI  - Intermittent versus continuous alkaline therapy for uric acid stones and ureteral
      stones of uncertain composition.

PMID- 14601586
TI  - HIV type 1 C and C' subclusters based on long terminal repeat sequences in the
      Ethiopian type 1 subtype C epidemic.
AB  - While the Ethiopian HIV-1 epidemic is dominated by subtype C, two distinguishable
      cocirculating C genotypes have been identified based on sequences of the C2V3
      envelope region. In this study we sequenced and analyzed the long terminal repeat
      (LTR) sequence from 22 Ethiopian HIV-1-positive individuals. The two
      phylogenetically distinguishable genotypes C (n = 13) and C' (n = 4) are
      separated by significant bootstrap values. Nucleotide differences between the two
      groups were identified in the NF-AT, TCF-1alpha, and SP1 transcription factor
      binding sites, whereas the NF-kappaB and NRE-core sequences were identical
      between the two groups. Five isolates that could not be classified C or C' were
      found to be recombinants within the LTR sequence upon boots can analysis.
      Comparison of all the LTR sequences with their corresponding C2V3 envelope
      sequence revealed four intersubtype C/C' recombinant isolates. Thus, the
      prevalence of C/C' recombinant viruses is well over 40%. Interestingly, the C2V3
      envelope sequences of all recombinant viruses belonged to the genotype C',
      whereas every LTR sequence belonged to the genotype C. This result indicates that
      recombination between the two genotypes is unidirectional, possibly as the result
      of evolutionary pressure on the respective biological functions of the LTR
      promoter and the envelope protein.

PMID- 14601588
TI  - Efficacy and outcome of surgical intervention in patients with nephrolithiasis
      and chronic renal failure.

PMID- 14601587
TI  - Role of Oxalobacter formigenes in calcium oxalate stone disease: a study from
      North India.

PMID- 14601589
TI  - Flexible ureteroscopes: a user's guide.

PMID- 14601591
TI  - Flexible ureterorenoscopy for the treatment of lower pole calyx stones: influence
      of different lithotripsy probes and stone extraction tools on scope reflection
      and irrigation flow.

PMID- 14601590
TI  - Conservation of the human immunodeficiency virus type 1 gp120 V1/V2 stem/loop
      structure in the equine infectious anemia virus (EIAV) gp90.

PMID- 14601592
TI  - HIV type 1 isolates from 200 untreated individuals in Ho Chi Minh City (Vietnam):
      ANRS 1257 Study.  Large predominance of CRF01_AE and presence of major resistance
      mutations to antiretroviral drugs.
AB  - HIV-1 isolates from 200 untreated patients recruited in 2001 and 2002 in the
      south part of Vietnam and particularly in Ho Chi Minh City were sequenced in the
      RT, protease, and env genes. Out of 200 isolates 198 belonged to CRF01_AE while
      only one subtype B and one intersubtype (B-CRF01_AE) recombinant could be
      observed. Of the isolates 6.5% had major resistance mutations to antiretroviral
      drugs.

PMID- 14601593
TI  - Ureteroscopic treatment of renal calculi in morbidly obese patients: a stone
      matched comparison.

PMID- 14601594
TI  - Ureteroscopy and holmium: YAG laser lithotripsy: an emerging definitive
      management strategy for symptomatic ureteral calculi in pregnancy.

PMID- 14601595
TI  - Characterization of HIV type 1 clades in the Caribbean using pol gene sequences.
AB  - To date, 11 HIV-1 M group clades, A to K, have been characterized, displaying
      different distributions, prevalences, and biological properties. Approximately
      90% of new HIV-1 infections occur in developing countries, including the
      Caribbean. However, information on HIV-1 subtypes from this region is limited. We
      report subtype characterization of viruses from 71 individuals, obtained during
      the period 2000-2002. RNA from the pol region was sequenced, generating data on
      subtype and drug resistance associated mutations for 71 specimens from 9
      countries. Sixty-seven (94.4%) sequences were classified as clade B, three (4.2%)
      as D/B, and one (1.4%) as clade C. Numerous polymorphisms were observed,
      including some associated with drug resistance, but not signifying exposure to
      chemotherapy. This study adds to our knowledge of HIV-1 clades in the Caribbean,
      and indicates possibilities for monitoring HIV-1 chemotherapy.

PMID- 14601596
TI  - Special issue on quantitative understanding of transmissible spongiform
      encephalopathies such a BSE and CJD dedicated to the veterinary epidemiologist
      Professor John Wilesmith.

PMID- 14601598
TI  - The first clinical results of "wide-focus and low-pressure" ESWL.

PMID- 14601597
TI  - Molecular cloning and analysis of full-length genome of HIV type 1 strains
      prevalent in countries of the former Soviet Union.
AB  - The HIV-1 epidemic among injecting drug users (IDUs) in countries of the former
      Soviet Union (FSU) was caused mainly by two HIV-1 variants: subtype A and CRF03
      AB. To date only three full-length HIV-I genomes from the FSU have been
      sequenced: one subtype A from Byelorussia and two CRF03-AB from Russia. We report
      the full-length genome cloning and analysis of two more HIV-1 strains from the
      FSU countries (98UA0116 of subtype A and 98BY10443 of CRF03-AB). Isolate 98UA0116
      is the second cloned and sequenced full-length HIV-1 genome of subtype A lineage
      from the FSU, which may be a novel subsubtype within sub-type A. Isolate
      98BY10443 is the third full-length HIV-1 genome of CRF03-AB in the world to be
      cloned and sequenced. Additionally, it is the first CRF03-AB strain discovered in
      Byelorussia. Cloned genomic sequences of the FSU HIV-1 isolates are being used
      for the development of a region-specific HIV-1 vaccine.

PMID- 14601599
TI  - Putting CPOE to work.

PMID- 14601600
TI  - Get results with workload measurement.

PMID- 14601601
TI  - Effect of overpressure and pulse repetition frequency on cavitation in shock wave
      lithotripsy.

PMID- 14601602
TI  - Conservative management of upper urinary tract tumors.

PMID- 14601604
TI  - Air embolism: diagnosis with single-photon emission tomography and successful
      hyperbaric oxygen therapy.

PMID- 14601603
TI  - Special issue in honor of William H Orme-Johnson.

PMID- 14601605
TI  - Anderson-Hynes dismembered pyeloplasty performed using the da Vinci robotic
      system.

PMID- 14601606
TI  - Assessment of basic endoscopic performance using a virtual reality simulator.

PMID- 14601608
TI  - Prospective analysis of circulating endostatin levels in patients with renal cell
      carcinoma.

PMID- 14601609
TI  - Molecular epidemiology of VHL gene mutations in renal cell carcinoma patients:
      relation to dietary and other factors.

PMID- 14601610
TI  - Tuberous sclerosis-associated lesions of the kidney, brain, and skin are
      angiogenic neoplasms.

PMID- 14601611
TI  - Pregnancy outcome after treatment for Wilms tumor: a report from the National
      Wilms Tumor Study Group.

PMID- 14601612
TI  - United States radiation oncologists' and urologists' opinions about screening and
      treatment of prostate cancer vary by region.

PMID- 14601613
TI  - Unexplained extra visits to general practitioners before the diagnosis of first
      urinary tract infection: a case-control study.

PMID- 14601614
TI  - The use of models in the estimation of disease epidemiology.

PMID- 14601615
TI  - Risk factors for recurrent urinary tract infection in young women.

PMID- 14601616
TI  - Medium-term follow-up of transvaginal suburethral slings: variance in outcome
      success using two different evaluation methods.

PMID- 14601617
TI  - Abstracts of the American Society of Nephrology 2003 Renal Week. November 12-17,
      2003. San Diego, California, USA.

PMID- 14601618
TI  - Abstracts of the 25th Annual Meeting of the American Society for Bone and Mineral
      Research. Minneapolis, Minnesota, USA. September 19-23, 2003.

PMID- 14601619
TI  - Abstracts of the annual meeting of the European Academy of Childhood Disability.
      2-4 October 2003, Oslo, Norway.

PMID- 14601620
TI  - Bibliography of toxinology.

PMID- 14601621
TI  - Abstracts of the 12th North American ISSX Meeting. October 12-16, 2003.
      Providence, Rhode Island, USA.

PMID- 14601622
TI  - [Alzheimer 2003. Abstracts of the 7th Francophone meeting on Alzheimer disease
      and the French Society of Geriatrics meeting. Paris, France, 7-10 October 2003].

PMID- 14601623
TI  - Looking for leadership.

PMID- 14601624
TI  - Hospital CEO turnover contines decline in 2002.

PMID- 14601625
TI  - Video views and reviews.

PMID- 14601626
TI  - WWW. Cell Biology Education.

PMID- 14601627
TI  - Cellular events preceding acetaminophen cataractogenesis studied by confocal
      fluorescence microscopy.
AB  - Acetaminophen (APAP) is biotransformed by hepatic cytochrome P450 (CYP) enzymes
      to the cataractogenic metabolite N-acetyl-p-benzoquinone imine (NAPQI). In the
      previous studies in which NAPQI was injected into the anterior chamber of mouse
      eye, we observed mitochondrial dysfunction and disturbances in Ca2+ homeostasis
      in the lens epithelium, and activation of the nonlysosomal neutral protease
      calpain. In this work we investigated whether intraperitoneal injection of APAP
      elicits similar cellular responses in the lens epithelium prior to the onset of
      lens opacity development. Following APAP injection, reactive oxygen species
      generation, intracellular free Ca2+ increase and calpain activation in the lens
      epithelium were determined in situ by fluorescence confocal microscopy. It was
      found that cellular events in the lens prior to the onset of opacification were
      essentially identical to those elicited by NAPQI. In addition, lens calpain
      activities were characterized based on their Ca2+ requirement and several calpain
      inhibitors were shown to prevent cataract development.

PMID- 14601631
TI  - Thrombolysis for acute ischaemic stroke: revisiting the evidence.

PMID- 14601632
TI  - Thrombolysis for acute ischaemic stroke: revisiting the evidence.

PMID- 14601633
TI  - [Specialty education in otorhinolaryngology and head and neck surgery].

PMID- 14601634
TI  - Genomic instability and cancer.
AB  - Tumorigenesis can be viewed as an imbalance between the mechanisms of cell-cycle
      control and mutation rates within the genes. Genomic instability is broadly
      classified into microsatellite instability (MIN) associated with mutator
      phenotype, and chromosome instability (CIN) recognized by gross chromosomal
      abnormalities. Three intracellular mechanisms are involved in DNA damage repair
      that leads to mutator phenotype. They include the nucleotide excision repair
      (NER), base excision repair (BER) and mismatch repair (MMR). The CIN pathway is
      typically associated with the accumulation of mutations in tumor suppressor genes
      and oncogenes. Defects in DNA MMR and CIN pathways are responsible for a variety
      of hereditary cancer predisposition syndromes including hereditary non-polyposis
      colorectal carcinoma (HNPCC), Bloom syndrome, ataxia-telangiectasia, and Fanconi
      anaemia. While there are many genetic contributors to CIN and MIN, there are also
      epigenetic factors that have emerged to be equally damaging to cell-cycle
      control. Hypermethylation of tumor suppressor and DNA MMR gene promoter regions,
      is an epigenetic mechanism of gene silencing that contributes to tumorigenesis.
      Telomere shortening has been shown to increase genetic instability and tumor
      formation in mice, underscoring the importance of telomere length and telomerase
      activity in maintaining genomic integrity. Mouse models have provided important
      insights for discovering critical pathways in the progression to cancer, as well
      as to elucidate cross talk among different pathways. This review examines various
      molecular mechanisms of genomic instability and their relevance to cancer.

PMID- 14601635
TI  - Aberrant regulation of translation initiation in tumorigenesis.
AB  - Altering the rate of translation initiation of a specific gene can tightly
      regulate the synthesis of the corresponding polypeptide and is an important
      mechanism in the control of gene expression. For some time it has been known that
      many genes involved in cell proliferation, cell growth and apoptosis have
      atypical 5' untranslated regions (UTRs) containing a high degree of RNA secondary
      structure, upstream open reading frames and internal ribosome entry segments.
      These features play a key role in the regulation of protein synthesis. In this
      review we discuss how the rate of translation initiation of proto-oncogenes and
      tumour suppressor genes is affected by elements in their 5' and 3' UTRs and we
      focus on how changes in the controlof gene expression at this level can
      contribute towards tumorigenesis.

PMID- 14601636
TI  - The quest for a tumor suppressor gene phenotype.
AB  - Our current definitions of the tumor suppressor gene (TSG) have been guided by
      the identification of the prototypical gene, RB1, a TSG that is implicated in the
      development of both the inherited and sporadic forms of retinoblastoma. The
      hallmark feature of this TSG is loss of function in tumoral cells, which can be
      restored by reintroduction of a normally functioning protein with concomitant
      reversion of tumorigenicity. Key to this discovery was that loss of function is
      often achieved by deletion of a normal copy of the TSG and retention of a mutated
      allele, which was either inherited or acquired. Suppression of tumorigenicity and
      the loss-of-function concept of TSGs was also demonstrated in early studies where
      normal cellular growth was achieved when tumorigenic cells were fused with normal
      cells. Thus loss of genetic content and restoration of gene function has guided
      studies aimed at the discovery of novel TSGs. Here we review the successes of TSG
      discovery using three approaches that are based on the genetic analysis of
      inherited predisposition to cancer, tumors that display chromosome loss, and
      tumorigenic cells that display a suppression of tumorigenicity as a result of
      transfer of normal chromosomes. Based on a review of the literature we conclude
      that the discovery of TSGs has been highly successful in the genetic analysis of
      inherited predisposition to cancer with a dominant mode of inheritance. In
      contrast, the latter two approaches have yielded a paucity of TSGs that exhibit
      features similar to the prototypical RB1 in that they are rarely inactivated by
      somatic mutations in tumors displaying LOH, although decreased gene expression is
      observed. Nevertheless, some of these genes have been shown to suppress
      tumorigenicity when normal function is restored in tumorigenic cells consistent
      with the loss-of-function concept. These observations continue to challenge our
      current definition of TSG.

PMID- 14601637
TI  - The role of apoptosis in tumor progression and metastasis.
AB  - Metastasis, the process by which cancer spreads from a primary to a secondary
      site, is responsible for the majority of cancer related deaths. Yet despite the
      detrimental effects of metastasis, it is an extremely inefficient process by
      which very few of the cells that leave the primary tumor give rise to secondary
      tumors. Metastasis can be considered as a series of sequential steps that begins
      with a cell leaving a primary tumor, and concludes with the formation of a
      metastatic tumor in a distant site. During the process of metastasis cells are
      subjected to various apoptotic stimuli. Thus, in addition to genetic changes that
      promote unregulated proliferation, successful metastatic cells must have a
      decreased sensitivity to apoptotic stimuli. As many cancer cells exhibit
      aberrations in the level and function of key apoptotic regulators, exploiting
      these alterations to induce tumor cell apoptosis offers a promising therapeutic
      target. This review will examine the apoptotic regulators that are often
      aberrantly expressed in metastatic cells; the role that these regulators may play
      in metastasis; the steps of metastasis and their susceptibility to apoptosis; and
      finally, current and future cancer prognostics and treatment targets based on
      apoptotic regulators.

PMID- 14601638
TI  - Fundamental concepts of the angiogenic process.
AB  - The process of angiogenesis encompasses the growth and regression of capillary
      blood vessels. Angiogenesis is finely regulated at the molecular and genetic
      levels, not unlike other physiologic processes such as coagulation, glucose
      metabolism, and blood pressure. During the development of the field of
      angiogenesis research over the past three decades, fundamental concepts have been
      introduced along the way in an attempt where possible, to unify new data from a
      variety of different laboratories. I have assembled here the major concepts which
      underlie the angiogenic process as we currently understand it. Many of these are
      now taken for granted, but this was not always the case, and I have tried to show
      how they were developed. My goal is to provide a conceptual framework for those
      basic scientists or clinicians who may enter this rapidly expanding field. Each
      concept discussed here is accompanied by a few key references as a guide to the
      pertinent literature.

PMID- 14601639
TI  - Role of maspin in tumor metastasis and angiogenesis.
AB  - Cancer is one of the leading causes of mortality in developed countries such as
      the USA. In 1998, there were more than 280,000 and 250,000 cancer related deaths
      in males and females, respectively. In males, lung and prostate cancers accounted
      for almost half of these deaths, whereas in females, lung and breast cancers were
      the leading causes of cancer mortalities. Therefore, the study of cancer has been
      of the utmost importance to patients, doctors, and researchers alike. A variety
      of cellular processes occur in the precancerous cells that contribute to the
      development and progression to cancer. Not surprisingly, all of these cellular
      processes have been targeted for anticancer therapy. A novel serpin, maspin, has
      demonstrated a robust effect on a variety of these cancer progression steps. A
      number of studies have shown that maspin inhibits angiogenesis and tumor cell
      growth and invasion both in vitro and in vivo. In addition, maspin promotes cell
      adhesion to the basement membrane and extracellular matrix components. Efforts
      underway to understand the molecular mechanisms involved in the diverse functions
      influenced by maspin have yielded promising results and shed light on the cancer
      pathways.

PMID- 14601640
TI  - Molecular mechanisms of tumor invasion and metastasis: an integrated view.
AB  - As tumors progress to increased malignancy, cells within them develop the ability
      to invade into surrounding normal tissues and through tissue boundaries to form
      new growths (metastases) at sites distinct from the primary tumor. The molecular
      mechanisms involved in this process are incompletely understood but those
      associated with cell-cell and cell-matrix adhesion, with the degradation of
      extracellular matrix, and with the initiation and maintenance of early growth at
      the new site are generally accepted to be critical. This article discusses
      current knowledge of molecular events involved in these various processes. The
      potential role of adhesion molecules (eg. integrins and cadherins) has undergone
      a major transition over the last ten years, as it has become apparent that such
      molecules play a major role in signaling from outside to inside a cell, thereby
      controlling how a cell is able (or not) to sense and interact with its local
      environment. Similarly the roles of proteolytic enzymes and their inhibitors (eg.
      matrix metalloproteinases and TIMPs) have also expanded as it has become apparent
      that they not only have the abilities to break down the components of the
      extracellular matrix but also are involved in the release of factors which can
      affect the growth of the tumor cells positively or negatively. Recent work has
      highlighted the importance of the later, post-extravasational stages of
      metastasis, where adhesion and proteolysis are now known to play a role along
      with other processes such as apoptosis, dormancy, growth factor-receptor
      interactions and signal transduction. Recent work has also demonstrated that not
      only the immediate cellular microenvironment, in terms of specific cell-cell and
      cell-matrix interactions, but also the extended cellular microenvironment, in
      terms of vascular insufficiency and hypoxia in the primary tumor, can modify
      cellular gene expression and enhance metastasis. Mechanisms of metastasis appear
      to involve a complex array of genetic and epigenetic changes many of which appear
      to be specific both for different types of tumors and for different sites of
      metastasis. Our improved understanding of the expanded roles of the individual
      molecules involved has resulted in a mechanistic blurring of the previously
      described discrete stages of the metastatic process.

PMID- 14601641
TI  - Receptor-mediated choreography of life and death.
AB  - The cytokine tumor necrosis factor was originally identified as a protein that
      kills tumor cells. So far, 18 distinct members of this family have been
      identified. All of them regulate cell survival, proliferation, differentiation,
      and cell death, also called apoptosis. The apoptosis induced by TNF, and other
      members of the family, for example, FasL, VEGI, and TRAIL is mediated through
      death receptors. The apoptotic signals by these cytokines are transduced by eight
      different death domain- (DD) containing receptors (TNFR1, also called DR1; Fas,
      also called DR2; DR3, DR4, DR5, DR6, NGFR, and EDAR). The intracellular portion
      of all these receptors contains a region approximately 80 amino acids long
      referred to as the "death domain." Upon activation by its ligand, the DD recruits
      various proteins that mediate both death and proliferation of the cells. These
      proteins in turn recruit other proteins via their DDs or death effector domains.
      The actual destruction of the cell, however, is accomplished by serial activation
      of a family of proteases referred to as caspases. Cell death is negatively
      regulated by a family of proteins that includes decoy receptors, silencer of DD,
      sentrin, cellular FLICE inhibitory protein, cellular inhibitors of apoptosis, and
      survivin. This review is an attempt to describe how these negative and positive
      players of cell death perform a harmonious dance with each other.

PMID- 14601643
TI  - p53's believe it or not: lessons on transcription-independent death.
AB  - The requirement for an intact p53 signaling pathway to sense tumor-promoting DNA
      damage is evident from over 20 years of molecular, cellular, and whole animal
      studies. Without a doubt, p53's major contribution in maintaining the genomic
      integrity of multicellular organisms is through transcriptional regulation of
      genes required for cell cycle arrest, DNA repair, and apoptosis. Nonetheless,
      evidence is mounting that p53 has an extranuclear role in the cytoplasm to induce
      apoptosis, perhaps coupled to its transcriptional effects, or conceivably at
      instances when transcription is not optimal or possible. This phenomenon,
      transcription-independent p53-induced apoptosis (TIPA), has been described for
      almost 10 years, yet little is known about mechanisms by which p53 can directly
      engage the apoptotic cascade in the absence of transcription. Here we will
      explore what is currently known about TIPA learned from various p53 mutants and
      truncations, along with discussing several proposed mechanisms.

PMID- 14601644
TI  - Fas ligand-mediated apoptosis in degenerative disorders of the brain.
AB  - While defective apoptosis predisposes to neoplasia, inappropriate apoptosis in
      the brain leads to permanent neurological deficits. Disregulated apoptosis has
      been implicated in several neurodegenerative disorders including Alzheimer's,
      Parkinson's, and Huntington's diseases. Recent reports have suggested that the
      key apoptosis regulator Fas ligand (FasL) may participate in both neuronal and
      immune cell apoptosis in Alzheimer's disease. FasL has also been implicated as a
      negative regulator for the inflammatory component of the demyelinating brain
      disorder multiple sclerosis (MS). Here, we discuss how FasL-mediated apoptosis
      may balance immune cell access to the brain with Alzheimer's disease and MS
      representing extremes of too little and too much immune access, respectively.

PMID- 14601642
TI  - The "fuzzy logic" of the death-inducing signaling complex in lymphocytes.
AB  - Receptors belonging to the tumor necrosis factor receptor family have long been
      thought to play an important role in the regulation of immunity. Although this
      family is composed of a large number of surface receptors that potentiate myriad
      functions in vivo, a subset is known to directly convey apoptotic signals. One
      such molecule belonging to this subset is CD95. Ligation of CD95 instigates the
      formation of a complex known as the "death-inducing signaling complex" or DISC,
      which is composed of molecules including FADD (Fas associated with death domain)
      and RIP (receptor-interacting kinase), as well as procaspases-8 and -10, and a
      caspase-8-like molecule that lacks proteolytic activity called c-FLIP. Although
      the DISC was initially thought to serve an exclusively proapoptotic role, humans
      and mice with defects in various components of this complex demonstrate a variety
      of developmental and hematopoietic defects that are not apparently due to
      aberrant apoptosis. These findings paint a far more complex picture of the
      numerous components of the DISC, and provide evidence that these complexes serve
      nonapoptotic functions. Herein, we summarize the experimental evidence
      challenging the notion that the DISC imparts an exclusively apoptotic function
      and provide hypotheses to account for these alternative roles. Rather than
      operating as a binary system, we propose that the DISCs formed around various DRs
      transduce signals leading to a variety of cellular fates.

PMID- 14601645
TI  - Immune abnormalities induced by human endogenous retroviral peptides: with
      reference to the pathogenesis of systemic lupus erythematosus.
AB  - P15E is a specific sequence among the envelope gene (env)-encoded transmembrane
      proteins of exogenous and endogenous retroviruses. A synthetic peptide (CKS- 17)
      that shows homology to this p15E region in several species of retrovirus is known
      to induce immune abnormalities. In this study, we examined the effect of a
      synthetic peptide derived from a region of human endogenous retrovirus (HERV)
      clone 4-1 (lambda4 - 1) similar to sequences of CKS-17 on the induction of
      systemic lupus erythematosus (SLE)-related immune abnormalities. Our results
      indicated that this peptide could induce T-cell activation and anergy in normal
      peripheral blood mononuclear cells, and the peptide could also promote the
      production of interleukins IL-6 and IL-16. These phenomena are representative
      immune abnormalities observed in SLE patients. Thus, our findings support the
      possibility that HERV acts as a pathogen in human SLE.

PMID- 14601646
TI  - Prevalence and clinical correlations of antibodies against six beta2-glycoprotein
      I-related peptides in the antiphospholipid syndrome.
AB  - Two-hundred ninety five patients with the antiphospholipid syndrome (APS) were
      studied for the presence of antibodies against six anti-beta2GPI-related peptides
      Abs. The prevalence of a wide spectrum of clinical and laboratory parameters of
      APS was evaluated in all patients, and correlated with the presence of each anti
      beta2GPI peptide antibody. The rates of the various antipeptides Abs ranged from
      18.0 to 63.7%. Altogether, 87.1% of the patients had antibody reactivity against
      at least one of the six beta2GPI-related peptides. A high degree of simultaneous
      reactivity against several beta2GPI-peptides was found. Positive and negative
      correlations were found between several antipeptides Abs and the rates of
      thrombosis and fetal loss. Our results point to a heterogeneous activity of
      antiphospholipid Abs in APS patients, directed, often concurrently, against
      various epitopes of the beta2GPI molecule. Evaluation of APS patients for the
      presence of specific antipeptides Abs may be of a value in predicting the risk
      for future thrombotic and obstetrical complication, as well as for specific
      therapeutic purposes.

PMID- 14601647
TI  - Common variable immunodeficiency patient classification based on impaired B cell
      memory differentiation correlates with clinical aspects.
AB  - Common variable immunodeficiency (CVID) is a very heterogeneous syndrome defined
      by impaired immunoglobulin production. The functional classification of CVID
      patients on the basis of in vitro immunoglobulin production is time consuming and
      has never shown any predictive value. We propose a classification based on the
      quantitative repartition of naive/memory B cells according to the dual expression
      of IgD and CD27. Fifty-seven patients were categorized into three groups: Group
      MB2 (11 patients, 19%) with normal memory B cells; Group MB1 (19 patients, 33%)
      with defective switched memory (IgD-CD27+) but normal nonswitched memory B cells
      (IgD+CD27+); Group MB0 (27 patients, 47%) with almost no memory B cells. In
      addition, a downexpression of activation markers (CD25, CD21, CD80, CD86) on B
      cells characterized the group MB1 patients and was associated with an
      upexpression of activation markers (HLA-DR, CD95, CD57) on T cells. This
      classification correlates with some clinical aspects showing a higher prevalence
      of splenomegaly (16/27, 59%), lymphoid proliferation (13/27, 48%) and
      granulomatous disease (12/27, 44%) in group MB0. Splenomegaly was also frequent
      in group MB1 (8/19, 42%). In contrast, autoimmunity was observed with similar
      prevalence in all three groups. Moreover, by analyzing B cell phenotype,
      immunoglobulin transcript expression, and somatic mutations, we propose different
      putative mechanisms responsible for impaired B cell activation and memory
      differentiation in this syndrome.

PMID- 14601648
TI  - Increased interleukin-7 plasma levels are associated with recovery of CD4+ T
      cells in HIV-infected children.
AB  - To asses the role of interleukin 7 (IL-7) in the thymic reconstitution of CD4 T
      cells observed in children after successful antiretroviral therapy, a
      longitudinal study in five vertically HIV-1-infected children was carried out.
      Thymic function, IL-7 plasma levels, viral load, and T-lymphocytes subsets were
      determined every 2 or 3 months for about 90 months. In all the children, the drop
      in CD4+ T cells below 5-10% was associated with a marked increase in IL-7 plasma
      levels. The drastic decrease in viral load after treatment, led in all the cases
      to a recover of CD4 to levels higher than 30%, which was associated to an
      increase in thymic production of T cells and followed by a decrease in IL-7 to
      the normal levels. We conclude that the drop in CD4 in HIV children would induce
      an increase of IL-7 as part of a homeostatic mechanism. IL-7 would induce the
      thymus to produce new T cells to recover the normal levels of CD4 when the viral
      load was low and so the thymic function was not inhibited. The increase in the
      thymic production of new T cells recovers the CD4 population, and leads to a
      normalization of IL-7 levels.

PMID- 14601649
TI  - Reduced IFN-gamma responses associated with HLA-DR15 presentation of
      streptococcal cell wall proteins to dermal Th-1 cells in psoriasis.
AB  - We have recently described a group A streptococcal (GAS)-reactive Th-1 subset
      specifically present in skin lesions of chronic plaque psoriasis. To investigate
      MHC presentation of GAS cell wall proteins, dermal T cell lines (TCL) cultured
      from the lesional skin of 39 HLA-typed psoriasis patients were stimulated with a
      cell wall extract, stained for intracellular IFN-gamma expression, and analyzed
      by flow cytometry. TCL from a further seven psoriasis patients were also tested
      with S. mutans extract. Eight TCL were tested in the presence of anti-Class II
      antibodies or allogeneic antigen-presenting cells. The dermal T cell IFN-gamma
      responses to the cell wall extract, which ranged from < 1 to 28%, were
      significantly higher than that to S. mutans extract (p = 0.0052) and were self
      HLA-DR allele restricted. A significantly decreased response was observed in TCL
      from DR15+ (n = 13) versus DR15- (n = 26) patients (p = 0.0377). In addition,
      DR15+ patients had a later age of onset of disease and a decreased history of
      sore throats. In contrast, TCL from HLA-DR7+ (n = 23) patients responded
      similarly to those from individuals lacking the DR7 allele. However, DR7+
      patients who coexpressed the MHC Class I antigen, Cw6 (n = 14) had a
      significantly higher IFN-gamma response than Cw6-, DR7+ patients (n = 7; p =
      0.0288) whose responses were also significantly lower than those of patients
      expressing non-DR7 alleles (n = 16; p = 0.0302). This study has shown that HLA
      DR15 expression is associated with a reduced dermal Th-1 response to GAS cell
      wall proteins in patients with psoriasis. It is proposed that HLA-DR allelic
      variation may contribute to disease phenotype via effects on the immune response
      to group A streptococci.

PMID- 14601650
TI  - Identification of an HLA-A0201-restricted CTL epitope generated by a tumor
      specific frameshift mutation in a coding microsatellite of the OGT gene.
AB  - Deficient DNA mismatch repair results in microsatellite instability and might
      induce shifts of translational reading frames of genes encompassing coding
      microsatellites. These may be translated in truncated proteins, including neo
      peptide tails functioning as tumor rejection antigens, when presented in the
      context of MHC class I. Recently, others and we identified a frameshift mutation
      in the coding T(10) microsatellite of the O-linked N-acetylglucosamine
      transferase gene (OGT) occuring in up to 41% of microsatellite unstable
      colorectal cancers. Here we describe a novel HLA-A0201-restricted cytotoxic T
      lymphocyte (CTL)-epitope (28-SLYKFSPFPL; FSP06) derived from this mutant OGT
      protein. FSP06-specific CTL-clones killed peptide-sensitized target cells and
      tumor cell lines expressing both HLA-A0201 and mutant OGT proteins. This
      demonstrates that FSP06 is endogenously expressed and represents a CD8(+)-T cell
      epitope. Our data corroborate the concept of frameshift peptides constituting a
      novel subset of tumor-associated antigens specifically encountered in cancer
      cells with deficient mismatch repair.

PMID- 14601651
TI  - Upregulation of neurokinin-1 receptor expression in the lungs of patients with
      sarcoidosis.
AB  - Substance P (SP) is a proinflammatory neuropeptide that is secreted by sensory
      nerves and inflammatory cells. Increased levels of SP are found in sarcoid
      bronchoalveolar lavage fluid. SP acts by binding to the neurokinin-1 receptor and
      increases secretion of tumor necrosis factor-alpha in many cell types. We sought
      to determine neurokinin-1 receptor expression in patients with sarcoidosis
      compared with normal controls. Neurokinin-1 receptor messenger RNA and protein
      expression were below the limits of detection by reverse transcriptase-polymerase
      chain reaction and immunohistochemistry in peripheral blood mononuclear cells of
      healthy volunteers (n = 9) or patients with stage 1 or 2 pulmonary sarcoidosis (n
      = 10), but were detected in 1/9 bronchoalveolar lavage cells of controls compared
      with 8/10 patients with sarcoidosis (p = 0.012) and 2/9 biopsies of controls
      compared with 9/10 patients with sarcoidosis (p = 0.013). Immunohistochemistry
      localized upregulated neurokinin-1 receptor expression to bronchial and alveolar
      epithelial cells, macrophages, lymphocytes, and sarcoid granulomas. The patient
      in whom neurokinin-1 receptor was not detected was taking corticosteroids.
      Incubation of the type II alveolar and bronchial epithelial cell lines A549 and
      SK-LU 1 with dexamethasone downregulated neurokinin-1 receptor expression.
      Upregulated neurokinin-1 receptor expression in patients with sarcoidosis may
      potentiate substance P-induced proinflammatory cytokine production in patients
      with sarcoidosis.

PMID- 14601652
TI  - Chemically regulated expression systems and their applications in transgenic
      plants.
AB  - In the past 20 years, several systems have been developed to control transgene
      expression in plants using chemicals. The components used to construct these
      systems are derived from regulatory sequences mostly from non-plant organisms
      such as bacteria, fungi, insects and mammals. These constructs allowed transgene
      expression to be controlled temporally, spatially and quantitatively with the
      help of exogenous chemicals, without disturbing endogenous plant gene expression.
      Various chemically regulated transgene expression systems, their
      advantages/disadvantages and their potential for large-scale field application
      are reviewed.

PMID- 14601654
TI  - Pea lectin expressed transgenically in oilseed rape reduces growth rate of pollen
      beetle larvae.
AB  - In several studies plant lectins have shown promise as transgenic resistance
      factors against various insect pests. We have here shown that pea seed lectin is
      a potential candidate for use against pollen beetle, a serious pest of Brassica
      oilseeds. In feeding assays where pollen beetle larvae were fed oilseed rape
      anthers soaked in a 1% solution of pea lectin there was a reduction in survival
      of 84% compared to larvae on control treatment and the weight of surviving larvae
      was reduced by 79%. When a 10% solution of pea lectin was used all larvae were
      dead after 4 days of testing. To further evaluate the potential use of pea
      lectin, transgenic plants of oilseed rape (Brassica napus cv. Westar) were
      produced in which the pea lectin gene under control of the pollen-specific
      promoter Sta44-4 was introduced. In 11 out of 20 tested plants of the T0
      generation there was a significant reduction in larval weight, which ranged up to
      46% compared to the control. A small but significant reduction in larval survival
      rate was also observed. In the T2-generation significant weight reductions, with
      a maximum of 32%, were obtained in 10 out of 33 comparisons between transgenic
      plants and their controls. Pea lectin concentrations in anthers of transgenic T2
      plants ranged up to 1.5% of total soluble protein. There was a negative
      correlation between lectin concentration and larval growth. Plants from test
      groups with significant differences in larval weights had a significantly higher
      mean pea lectin concentration, 0.64% compared to 0.15% for plants from test
      groups without effect on larval weight. These results support the conclusion that
      pea lectin is a promising resistance factor for use in Brassica oilseeds against
      pollen beetles.

PMID- 14601653
TI  - The transgenic rabbit as model for human diseases and as a source of biologically
      active recombinant proteins.
AB  - Until recently, transgenic rabbits were produced exclusively by pronuclear
      microinjection which results in additive random insertional transgenesis;
      however, progress in somatic cell cloning based on nuclear transfer will soon
      make it possible to produce rabbits with modifications to specific genes by the
      combination of homologous recombination and subsequent prescreening of nuclear
      donor cells. Transgenic rabbits have been found to be excellent animal models for
      inherited and acquired human diseases including hypertrophic cardiomyopathy,
      perturbed lipoprotein metabolism and atherosclerosis. Transgenic rabbits have
      also proved to be suitable bioreactors for the production of recombinant protein
      both on an experimental and a commercial scale. This review summarizes recent
      research based on the transgenic rabbit model.

PMID- 14601655
TI  - Biologically active human interferon alpha-2b produced in the egg white of
      transgenic hens.
AB  - We have previously described the expression of a bacterial protein in the egg
      white of transgenic chickens using a replication-deficient retroviral vector.
      Here we report the expression of a glycosylated human protein, interferon alpha
      2b (hIFN), in the egg white of transgenic hens. The hIFN secreted into the egg
      white was biologically active as determined by a viral inhibition assay.
      Purification and carbohydrate analysis of the hIFN expressed in egg white
      revealed that two of the six major glycosylated hIFN species match the naturally
      occurring human hIFN glycovariants. These results support the potential of the
      hen as a bioreactor for the production of commercially valuable, biologically
      active, and glycosylated proteins in egg white.

PMID- 14601657
TI  - Generation of rye (Secale cereale L.) plants with low transgene copy number after
      biolistic gene transfer and production of instantly marker-free transgenic rye.
AB  - Rye is extremely recalcitrant to tissue culture and genetic transformation. We
      describe the efficient and reproducible production of stably expressing
      transgenic rye plants after biolistic gene transfer to callus tissue derived from
      immature embryos. Key factors in the production of transgenic rye plants include
      the identification of biolistic gene transfer parameters and a selection
      protocol, which does not affect its regeneration ability. The bar gene was used
      as a selectable marker and selection was performed by spraying the regenerated
      shoots with 0.05% Basta solution without any previous selection of tissue
      cultures. Based on Southern blot analysis, a total of 21 transgenic rye plants
      with independent transgene integration patterns were produced. A low transgene
      copy number was observed in most transgenic plants and 40% of the plants had a
      single transgene copy insert. The high frequency of single transgene copy inserts
      might be a consequence of the selection system, which is based on the
      identification of stably expressing transgenic plantlets rather than stably
      expressing tissue cultures. All transgenic rye lines with single transgene
      inserts showed stable transgene expression in sexual progenies, but indications
      of transcriptional and post-transcriptional gene silencing were observed in few
      transgenic lines with multiple transgene inserts. Tissue culture-based selection
      was not necessary for the generation of transgenic rye. The identification of 17
      transgenic rye plants without using any selectable marker gene by PCR
      amplification of transgene sequences is also demonstrated. Instant generation of
      selectable marker-free transgenic rye avoids a negative impact of selective
      agents on the transgenic tissue cultures, responds to public concerns on the
      safety of selectable markers and will support multiple transformation cycles for
      transgene pyramiding.

PMID- 14601656
TI  - Induction of H2O2 in transgenic rice leads to cell death and enhanced resistance
      to both bacterial and fungal pathogens.
AB  - Oxidative burst, mediated by hydrogen peroxide (H2O2), has been recognized as a
      key component of plant defense response during an incompatible interaction. To
      determine if elevated levels of H2O2 lead to cell death, activation of defense
      genes and enhanced resistance to diverse pathogens, transgenic rice plants
      expressing a fungal glucose oxidase gene (GOX) were generated using both
      constitutive and inducible expression systems. Constitutive or wound/pathogen
      induced expression of GOX also allowed us to determine the effectiveness of these
      systems in conferring long lasting resistance to various pathogens. Both
      constitutive and wound/pathogen-induced expression of GOX lead to increases in
      the endogenous levels of H2O2, which in turn caused cell death. Elevated levels
      of H2O2 also activated the expression of several defense genes and these
      transgenic plants showed enhanced resistance to both bacterial and fungal
      pathogens. In comparison to inducible expression, constitutive expression of GOX
      resulted in 3-10-fold higher levels of the GOX transcript and the corresponding
      enzymatic activity. Such increased levels of GOX, which would result in elevated
      levels of H2O2, caused improper seed set and decreased seed viability in
      transgenic plants constitutively expressing GOX. Our results suggest that
      pathogen inducible expression of heterologous genes may be a practical and robust
      way of generating broad spectrum disease resistance.

PMID- 14601658
TI  - Expression of lysostaphin in milk of transgenic mice affects the growth of
      neonates.
AB  - As an initial step towards enhancing mastitis resistance in dairy animals, we
      generated BLG-Lys transgenic mice that secrete lysostaphin, a potent
      antistaphylococcal protein, in their milk. In the current study, we continue our
      assessment of lysostaphin as a suitable antimicrobial protein for mastitis
      resistance and have investigated mammary gland development and function in three
      lines of transgenic mice. As the lines were propagated, there was a tendency for
      fewer BLG-Lys litters to survive to weaning (51% as compared to 90% for
      nontransgenic lines, p = 0.080). Nontransgenic pups fostered on dams from these
      three lines exhibited diminished growth rates during the first week of lactation.
      Rates of gain became comparable to pups on nontransgenic dams at later time
      points. Initial slow growth also resulted in decreased weaning weights for pups
      nursed by transgenic dams (15.35 +/- 0.27 g) when compared to pups delivered and
      nursed by nontransgenic dams (18.61 +/- 0.61 g; p < 0.001), but the effect was
      temporary, as similar weights were attained by adulthood. Milk yield at peak
      lactation was not different between BLG-Lys (0.79 +/- 0.33 g) and nontransgenic
      (0.91 +/- 0.38 g; p = 0.166) dams. Histological examination of the transgenic
      mammary glands during gestation revealed no differences when compared to control
      glands; however, at early lactational stages, the BLG-Lys glands exhibited less
      alveolar area than control glands and a delay in lobulo-alveolar maturation. The
      results clearly demonstrate reduced growth of neonates on BLG-Lys dams; whether
      the poor pup performance can be attributed to delayed mammary development or the
      gland development merely reflects reduced suckling stimuli from the pups remains
      to be determined.

PMID- 14601659
TI  - Transformation of tobacco with genes encoding Helianthus tuberosus agglutinin
      (HTA) confers resistance to peach-potato aphid (Myzus persicae).
AB  - The effects of the hta gene encoding Helianthus tuberosus agglutinin (HTA) on an
      insect in the order Homoptera were investigated. Homologous cDNAs of hta-a, hta
      b, hta-c and hta-d with CaMV35S as promoter were introduced into tobacco via
      Agrobacterium tumefaciens. Southern blot results showed that the exogenous hta
      gene was inserted into the genome of host plants, and northern blot analysis
      confirmed that hta was expressed in transgenic plants. A bioassay with peach
      potato aphid (Myzus persicae) demonstrated that transgenic plants had deleterious
      effects on the insect. The average population of aphids fed on transgenic T0
      plants during an 11-day assay decreased by 70%, compared controls. In transgenic
      plants of T1 generation, aphid fecundity inhibitions were 53.0% (hta-b) and 64.6%
      (hta-c), respectively. The development of aphids was notably retarded. We
      conclude that hta could be a novel and promising candidate for plant transgenic
      engineering against homopteran insect pests.

PMID- 14601660
TI  - Activation-tagged tobacco mutants that are tolerant to antimicrotubular
      herbicides are cross-resistant to chilling stress.
AB  - T-DNA activation tagging was used to generate tobacco mutants with increased
      tolerance to antimicrotubular herbicides and chilling stress. After
      transformation, protoplast-derived calli were screened for tolerance to
      treatments that affect microtubule assembly. In one screen mutants with tolerance
      to aryl carbamates (a blocker of microtubule assembly) were selected, the second
      screen was targeted to chilling-tolerant mutants that could survive for several
      months at 3 degrees C, a third screen combined both factors. The resistance of
      these mutants to aryl carbamates or chilling was accompanied by resistance of
      microtubules to these factors. The carbamate tolerant mutants were cross
      resistant to chilling stress. This was mirrored by an adaptive reorganization of
      microtubules and a reduction of microtubule dynamics in response to chilling. The
      analysis of these mutants suggests (1) that microtubule dynamics limit the
      tolerance to chilling and EPC, and (2) that the cold sensitivity of microtubules
      limits chilling tolerance in tobacco.

PMID- 14601662
TI  - "Mouse locator-UK": a networking tool for academic transgenic research in the UK.

PMID- 14601661
TI  - Expression of green fluorescent protein from bacterial and plastid promoters in
      tobacco chloroplasts.
AB  - The expression of the green fluorescent protein reporter gene (gfp) from the
      bacterial trc and plastid rrn and psbA promoters has been compared in
      transplastomic tobacco plants produced by microprojectile bombardment. The
      homoplasmic nature of the regenerated plants was confirmed by Southern blot
      analysis. Northern blot analysis indicated that plants expressing gfp from the
      rrn promoter contained 3-fold more gfp RNA than plants containing the psbA
      promoter and 12-fold more than plants with the trc promoter. Immunoblot analysis
      and fluorescence spectroscopy indicated that plants expressing gfp from the rrn
      promoter contained approximately 90-fold more green fluorescent protein (GFP)
      than plants containing the psbA or trc promoters. This study demonstrates that
      the bacterial trc promoter is significantly weaker than the plastid rrn promoter
      for expression of gfp in tobacco chloroplasts.

PMID- 14601663
TI  - Isolation of a polygalacturonase-inhibiting protein (PGIP) from wheat.
AB  - Evidence for the presence of a polygalacturonase-inhibiting protein (PGIP) from a
      monocotyledonous cereal is presented. A 40.3-kDa PGIP that was closely associated
      with the cell wall was acetone-extracted and purified from wheat (Triticum
      aestivum L.) leaves and stems. Wheat PGIP exhibited a highly selective inhibitory
      activity against endopolygalacturonase (EPG) from various fungi. Of nine EPG
      tested, wheat PGIP only inhibited EPG from Cochliobolus sativus, a pathogen of
      the tribe Poaceae. A short N-terminal amino acid sequence of wheat PGIP shows no
      similarity to any other characterized PGIP.

PMID- 14601664
TI  - Nitric oxide does not trigger early programmed cell death events but may
      contribute to cell-to-cell signaling governing progression of the Arabidopsis
      hypersensitive response.
AB  - Nitric oxide (NO) has been suggested to play a role in the hypersensitive
      response (HR). Single- and double-label fluorescence microscopy experiments were
      conducted using Arabidopsis leaves infected with Pseudomonas syringae pv. tomato
      DC3000 carrying either avrB or avrRpt2. Kinetics of NO production were followed
      by measurement of green 4-amino-5-methylamino-2',7'-difluorofluorescein (DAF-FM)
      triazole fluorescence in leaves coinfiltrated with DAF-FM diacetate. Kinetics of
      hypersensitive cell death were followed by measurement of cytoplasmic red
      fluorescence following internalization of coinfiltrated propidium iodide through
      compromised plasma membranes. Neither NO accumulation nor cell death was seen
      until approximately 3 h postinoculation of Columbia leaves with DC3000.avrB or
      approximately 5.5 h post-inoculation with DC3000.avrRpt2. Subsequent NO
      accumulation kinetics closely paralleled HR progression in both Columbia and ndr1
      1 mutant plants. These data established that NO accumulation does not happen
      sufficiently early for NO to be a signaling component controlling HR triggering.
      NO accumulation did contribute to the HR, as proven by an approximately 1-h delay
      in cell death kinetics caused by an NO scavenger or an NO synthase inhibitor. NO
      was first seen as punctate foci at the cell surface. Subsequent NO accumulation
      patterns were consistent with NO being an intercellular signal that functions in
      cell-to-cell spread of the HR.

PMID- 14601665
TI  - PhyA, a secreted protein of Xanthomonas oryzae pv. oryzae, is required for
      optimum virulence and growth on phytic acid as a sole phosphate source.
AB  - Xanthomonas oryzae pv. oryzae causes bacterial leaf blight, a serious disease of
      rice. We have identified a novel virulence deficient mutant (BXO1691) of X.
      oryzae pv. oryzae that has a Tn5 insertion in an open reading frame (phyA;
      putative phytase A) encoding a 373-amino acid (aa) protein containing a 28-aa
      predicted signal peptide. Extracellular protein profiles revealed that a 38-kDa
      band is absent in phyA mutants as compared with phyA+ strains. A BLAST search
      with phyA and its deduced polypeptide sequence indicated significant similarity
      with conserved hypothetical proteins in Xanthomonas axonopodis pv. citri and
      Xanthomonas campestris pv. campestris and limited homology to secreted phytases
      of Bacillus species. Homology modeling with a Bacillus phytase as the template
      suggests that the PhyA protein has a similar six-bladed beta-propeller
      architecture and exhibits conservation of certain critical active site residues.
      Phytases are enzymes that are involved in degradation of phytic acid (inositol
      hexaphosphate), a stored form of phosphate in plants. The phyA mutants exhibit a
      growth deficiency in media containing phytic acid as a sole phosphate source.
      Exogenous phosphate supplementation promotes migration of phyA X. oryzae pv.
      oryzae mutants in rice leaves. These results suggest that the virulence
      deficiency of phyA mutants is, at least in part, due to inability to use host
      phytic acid as a source of phosphate. phyA-like genes have not been previously
      reported to be involved in the virulence of any plant pathogenic bacterium.

PMID- 14601666
TI  - Interactions in the tomato rhizosphere of two Pseudomonas biocontrol strains with
      the phytopathogenic fungus Fusarium oxysporum f. sp. radicis-lycopersici.
AB  - The fungus Fusarium oxysporum f. sp. radicis-lycopersici causes foot and root rot
      of tomato plants, which can be controlled by the bacteria Pseudomonas fluorescens
      WCS365 and P. chlororaphis PCL1391. Induced systemic resistance is thought to be
      involved in biocontrol by P. fluorescens WCS365. The antifungal metabolite
      phenazine-1-carboxamide (PCN), as well as efficient root colonization, are
      essential in the mechanism of biocontrol by P. chlororaphis PCL1391. To
      understand the effects of bacterial strains WCS365 and PCL1391 on the fungus in
      the tomato rhizosphere, microscopic analyses were performed using different
      autofluorescent proteins as markers. Tomato seedlings were inoculated with
      biocontrol bacteria and planted in an F. oxysporum f. sp. radicis-lycopersici
      infested gnotobiotic sand system. Confocal laser scanning microscope analyses of
      the interactions in the tomato rhizosphere revealed that i) the microbes
      effectively compete for the same niche, and presumably also for root exudate
      nutrients; ii) the presence of either of the two bacteria negatively affects
      infection of the tomato root by the fungus; iii) both biocontrol bacteria
      colonize the hyphae extensively, which may represent a new mechanism in
      biocontrol by these pseudomonads; and iv) the production of PCN by P.
      chlororaphis PCL1391 negatively affects hyphal growth and branching, which
      presumably affects the colonization and infecting ability of the fungus.

PMID- 14601668
TI  - Biocontrol traits of Pseudomonas spp. are regulated by phase variation.
AB  - Of 214 Pseudomonas strains isolated from maize rhizosphere, 46 turned out to be
      antagonistic, of which 43 displayed clear colony phase variation. The latter
      strains formed both opaque and translucent colonies, designated as phase I and
      phase II, respectively. It appeared that important biocontrol traits, such as
      motility and the production of antifungal metabolites, proteases, lipases,
      chitinases, and biosurfactants, are correlated with phase I morphology and are
      absent in bacteria with phase II morphology. From a Tn5luxAB transposon library
      of Pseudomonas sp. strain PCL1171 phase I cells, two mutants exhibiting stable
      expression of phase II had insertions in gacS. A third mutant, which showed an
      increased colony phase variation frequency was mutated in mutS. Inoculation of
      wheat seeds with PCL1171 bacteria of phase I morphology resulted in efficient
      suppression of take-all disease, whereas disease suppression was absent with
      phase II bacteria. Neither the gacS nor the mutS mutant was able to suppress take
      all, but biocontrol activity was restored after genetic complementation of these
      mutants. Furthermore, in a number of cases, complementation by gacS of wild-type
      phase II sectors to phase I phenotype could be shown. A PCL1171 phase I mutant
      defective in antagonistic activity appeared to have a mutation in a gene encoding
      a lipopeptide synthetase homologue and had lost its biocontrol activity,
      suggesting that biocontrol by strain PCL1171 is dependent on the production of a
      lipopeptide. Our results show that colony phase variation plays a regulatory role
      in biocontrol by Pseudomonas bacteria by influencing the expression of major
      biocontrol traits and that the gacS and mutS genes play a role in the colony
      phase variation process. Therefore phase variation not only plays a role in
      escaping animal defense but it also appears to play a much broader and vital role
      in the ecology of bacteria producing exoenzymes, antibiotics, and other secondary
      metabolites.

PMID- 14601667
TI  - Natural resistance to Clover yellow vein virus in beans controlled by a single
      recessive locus.
AB  - We characterized the resistance of the common bean cv. Jolanda to Clover yellow
      vein virus no. 30 (ClYVV). After inoculation, the virus was detected in neither
      inoculated nor upper leaves, suggesting that the resistance operates at either
      the viral replication or cell-to-cell movement level. To analyze the mechanism of
      resistance, we developed a green fluorescent protein (GFP)-tagged ClYVV, and
      monitored GFP fluorescence at sites of infection on ClYVV-inoculated leaves. No
      GFP fluorescence was detected in Jolanda, whereas its expression in single cells
      and spread on inoculated leaves were observed clearly in susceptible cultivars.
      ClYVV-introduced Jolanda cells were found to be still viable; therefore, it is
      unlikely that the restriction of multiplication was due to rapid cell death.
      Genetic analysis indicated that a single recessive locus controlled the resistant
      phenotype of Jolanda. We designated this locus desc (determinant of
      susceptibility to ClYVV). Meanwhile, a spontaneous mutant virus that overcomes
      the resistance (ClYVV-Br) was isolated. Inoculation assays using chimeric viruses
      suggested that a viral genome-linked protein (VPg) might be the avirulence
      determinant. The resistance mechanism may be associated with the role of VPg in
      the viral infection cycle.

PMID- 14601669
TI  - Deletion of all Cochliobolus heterostrophus monofunctional catalase-encoding
      genes reveals a role for one in sensitivity to oxidative stress but none with a
      role in virulence.
AB  - The genome of the maize pathogen Cochliobolus heterostrophus encodes three
      unlinked monofunctional catalase-encoding (CAT) genes that singly or in
      combination could offer protection against the harmful effects of oxidative
      stress. Phylogenetic analysis placed the CAT2 and CAT3 proteins in a cluster with
      large subunit catalases (CAT3 has a secretory signal sequence and was grouped
      with known secreted catalases), whereas CAT1 clustered with small subunit
      catalases. Single, double, and triple cat mutants were created and screened for
      sensitivity to hydrogen peroxide and altered virulence on maize. All mutants
      deficient in CAT3 had enhanced sensitivity to hydrogen peroxide, as compared with
      wild type or with mutants deficient in CAT1, CAT2, or both. All catalase
      deficient mutants had normal virulence to maize. Thus, the secreted CAT3 protein
      protects the fungus from oxidative stress during vegetative growth, but members
      of this enzyme family, alone or in combination, are not essential for virulence.

PMID- 14601670
TI  - Restoration of defective cross talk in ssi2 mutants: role of salicylic acid,
      jasmonic acid, and fatty acids in SSI2-mediated signaling.
AB  - The Arabidopsis mutants ssi2 and fab2 are defective in stearoyl ACP desaturase,
      which causes altered salicylic acid (SA)- and jasmonic acid (JA)-mediated defense
      signaling. Both ssi2 and fab2 plants show spontaneous cell death, express PR
      genes constitutively, accumulate high levels of SA, and exhibit enhanced
      resistance to bacterial and oomycete pathogens. In contrast to constitutive
      activation of the SA pathway, ssi2 and fab2 plants are repressed in JA-mediated
      induction of the PDF1.2 gene, which suggests that the SSI2-mediated signaling
      pathway modulates cross talk between the SA and JA pathways. In this study, we
      have characterized two recessive nonallelic mutants in the ssi2 background,
      designated as rdc (restorer of defective cross talk) 2 and rdc8. Both ssi2 rdc
      mutants are suppressed in constitutive SA signaling, show basal level expression
      of PR-1 gene, and induce high levels of PDF1.2 in response to exogenous
      application of JA. Interestingly, while the rdc8 mutation completely abolishes
      spontaneous cell death in ssi2 rdc8 plants, the ssi2 rdc2 plants continue to show
      some albeit reduced cell death. Fatty acid (FA) analysis showed a reduction in
      16:3 levels in ssi2 rdc8 plants, which suggests that this mutation may limit the
      flux of FAs into the prokaryotic pathway of glycerolipid biosynthesis. Both rdc2
      and rdc8 continue to accumulate high levels of 18:0, which suggests that 18:0
      levels were responsible for neither constitutive SA signaling nor repression of
      JA-induced expression of the PDF1.2 gene in ssi2 plants. We also analyzed SA and
      JA responses of the fab2-derived shs1 mutant, which accumulates levels of 18:0
      over 50% lower than those in the fab2 plants. Even though fab2 shs1 plants were
      morphologically bigger than fab2 plants, they expressed PR genes constitutively,
      showed HR-like cell death, and accumulated elevated levels of SA. However, unlike
      the ssi2 rdc plants, fab2 shs1 plants were unable to induce high levels of PDF1.2
      expression in response to exogenous application of JA. Together, these results
      show that defective cross talk in ssi2 can be restored by second site mutations
      and is independent of morphological size of the plants, cell death, and elevated
      levels of 18:0.

PMID- 14601671
TI  - Activity of class III peroxidases in the defense of cotton to bacterial blight.
AB  - Cotton cotyledons displayed a hypersensitive reaction (HR) in the cultivar Reba
      B50 after infiltration with the avirulent race 18 from Xanthomonas campestris pv.
      malvacearum. Two sets of peroxidases were associated with the HR time course.
      Early but transient accumulation of peroxidase in material encapsulating the
      bacteria in intercellular areas was observed by immunocytochemistry at 3 h
      postinfection and coincided with the oxidative burst. Total guaiacol-peroxidase
      activity was highly increased in cells undergoing HR, from 12 h after treatment.
      Molecular characterization of seven cloned peroxidase genes revealed highly
      conserved B, D, and F domains, with similarities to plant class III peroxidases.
      Analysis of gene expression showed variation in transcript accumulation during
      both compatible (race 20) and incompatible interactions for four of these genes:
      pod2, pod3, pod4, and pod6. Pod4 and pod6 were more intensely up-regulated during
      resistance than during disease and in the control, while pod3 was specifically
      down-regulated during the HR after the oxidative burst. Pod2 was induced by
      pathogen infection and weakly stimulated in the control. These data suggest that
      cotton peroxidases may have various functions in the defense response to
      Xanthomonas infections.

PMID- 14601673
TI  - Electronic archiving of the CVMA journals--a reality at last.

PMID- 14601672
TI  - Molecular analysis of the pathway for the synthesis of thiol tripeptides in the
      model legume Lotus japonicus.
AB  - The thiol tripeptides, glutathione (GSH) and homoglutathione (hGSH), perform
      multiple roles in legumes, including protection against toxicity of free radicals
      and heavy metals. The three genes involved in the synthesis of GSH and hGSH in
      the model legume, Lotus japonicus, have been fully characterized and appear to be
      present as single copies in the genome. The gamma-glutamylcysteine synthetase
      (gamma(ecs)) gene was mapped on the long arm of chromosome 4 (70.0 centimorgans
      [cM]) and consists of 15 exons, whereas the glutathione synthetase (gshs) and
      homoglutathione synthetase (hgshs) genes were mapped on the long arm of
      chromosome 1 (81.3 cM) and found to be arranged in tandem with a separation of
      approximately 8 kb. Both genes consist of 12 exons of exactly the same size
      (except exon 1, which is similar). Two types of transcripts were detected for the
      gshs gene, which putatively encode proteins localized in the plastids and
      cytosol. Promoter regions contain cis-acting regulatory elements that may be
      involved in the plant's response to light, hormones, and stress. Determination of
      transcript levels, enzyme activities, and thiol contents in nodules, roots, and
      leaves revealed that gamma(ecs) and hgshs are expressed in all three plant
      organs, whereas gshs is significantly functional only in nodules. This strongly
      suggests an important role of GSH in the rhizobia-legume symbiosis.

PMID- 14601674
TI  - In support of bones and raw food diets.

PMID- 14601675
TI  - An ethicist's commentary on the dairy with bad husbandry.

PMID- 14601676
TI  - Foreign animal disease outbreaks, the animal welfare implications for Canada:
      risks apparent from international experience.
AB  - Any outbreak of an Office International des Epizooties List A disease, such as
      classical swine fever or foot and mouth disease, has severe consequences for
      animal welfare, livestock production, exports of animals and animal products, and
      the environment. The public concern with the animal welfare effects of methods of
      disease eradication that result in the destruction of large numbers of uninfected
      animals has initiated a reconsideration of disease eradication policy in Europe.
      In many recent List A disease epizootics, the financial cost of addressing animal
      welfare concerns in healthy animals has greatly exceeded the cost of stamping out
      disease in infected herds. In the event of a similar incursion in Canada, the
      number of animals subject to welfare slaughter will be far greater than the
      number of infected animals killed. Current national disease eradication plans in
      Canada do not address the animal welfare component of disease control methods.

PMID- 14601678
TI  - Novel perineal approach for repair of a urethrorectal fistula in a bulldog.
AB  - A urethrorectal fistula was diagnosed in a 10-week-old, intact male bulldog,
      presented with a history of urine dribbling from his anus. The fistula was
      ligated using a novel perineal approach, resulting in resolution of clinical
      signs. The described procedure is simpler and less invasive than previously
      described repairs.

PMID- 14601677
TI  - Comparison of humoral immune responses in dairy heifers vaccinated with 3
      different commercial vaccines against bovine viral diarrhea virus and bovine
      herpesvirus-1.
AB  - A randomized clinical trial was conducted to compare the humoral immune response
      to 3 different commercial vaccines in dairy heifers housed in 3 different dairy
      farms in Quebec. All heifers were seronegative to type 1 bovine viral diarrhea
      virus (BVDV) (Singer strain), type 2 BVDV (NVSL 125c strain), and bovine
      herpesvirus-1 (BHV-1) at the beginning of the trial. In addition, control heifers
      in group 1 remained seronegative to the 2 viruses till the end of the trial.
      Significant differences in humoral immune responses occurred among the 3
      commercial vaccines at 4 weeks and 6 months following vaccination. The vaccine in
      group 2 elicited higher mean antibody titers and seroconversion rates to both
      type 1 and type 2 BVDV than that in groups 3 or 4. Vaccines in groups 2 and 3
      induced higher mean antibody titers to BHV-1 than did the vaccine in group 4.

PMID- 14601679
TI  - Ameloblastic odontoma in the mandible of a llama.
AB  - A 4-year-old llama had an aggressive, multiloculated, expansile bone lesion
      involving the rostral mandible. The mandibular lesion was imaged using
      radiography and computed tomography. Antemortem diagnosis of an ossifying fibroma
      was made histologically. Postmortem findings showed the lesion to be limited to
      the mandible. Final diagnosis was ameloblastic odontoma.

PMID- 14601680
TI  - Sulfur-induced polioencephalomalacia in a herd of rotationally grazed beef
      cattle.
AB  - Central nervous system disease occurred in a herd of rotationally grazed beef
      cattle consuming water containing 3400 ppm sulfate. Clinical signs, pathologic
      findings, and high water sulfate levels confirmed the diagnosis of sulfur-induced
      polioencephalomalacia. The incidence of disease reduced when the herd was
      switched to a low sulfate water source.

PMID- 14601681
TI  - Bovine tuberculosis in elk (Cervus elaphus manitobensis) near Riding Mountain
      National Park, Manitoba, from 1992 to 2002.

PMID- 14601682
TI  - The 2nd Meeting of the Canadian Animal Health Laboratorians Network. May 4-7,
      2003, Ottawa, Canada.

PMID- 14601685
TI  - Trachael collapse in an adult goat.

PMID- 14601686
TI  - Practical bond considerations: acknowledging clients' time constraints.

PMID- 14601687
TI  - Canine cranial cruciate ligament rupture in profile.

PMID- 14601688
TI  - Images and reflections from Mayo Clinic heritage.

PMID- 14601689
TI  - The search for the perfect heart-healthy diet.

PMID- 14601690
TI  - Effect of a high saturated fat and no-starch diet on serum lipid subfractions in
      patients with documented atherosclerotic cardiovascular disease.
AB  - OBJECTIVE: To determine whether a diet of high saturated fat and avoidance of
      starch (HSF-SA) results in weight loss without adverse effects on serum lipids in
      obese nondiabetic patients. PATIENTS AND METHODS: Twenty-three patients with
      atherosclerotic cardiovascular disease participated in a prospective 6-week trial
      at the Christiana Care Medical Center in Newark, Del, between August 2000 and
      September 2001. All patients were obese (mean +/- SD body mass index [BMI],
      39.0+/-7.3 kg/m2) and had been treated with statins before entry in the trial.
      Fifteen obese patients with polycystic ovary syndrome (BMI, 36.1+/-9.7 kg/m2) and
      8 obese patients with reactive hypoglycemia (BMI, 46.8+/-10 kg/m2) were monitored
      during an HSF-SA diet for 24 and 52 weeks, respectively, between 1997 and 2000.
      RESULTS: In patients with atherosclerotic cardiovascular disease, mean +/- SD
      total body weight (TBW) decreased 5.2%+/-2.5% (P<.001) as did body fat percentage
      (P=.02). Nuclear magnetic resonance spectroscopic analysis of lipids showed
      decreases in total triglycerides (P<.001), very low-density lipoprotein (VLDL)
      triglycerides (P<.001), VLDL size (P<.001), large VLDL concentration (P<.001),
      and medium VLDL concentration (P<.001). High-density lipoprotein (HDL) and LDL
      concentrations were unchanged, but HDL size (P=.01) and LDL size (P=.02)
      increased. Patients with polycystic ovary syndrome lost 14.3%+/-20.3% of TBW
      (P=.008) and patients with reactive hypoglycemia lost 19.9%+/-8.7% of TBW
      (P<.001) at 24 and 52 weeks, respectively, without adverse effects on serum
      lipids. CONCLUSION: An HSF-SA diet results in weight loss after 6 weeks without
      adverse effects on serum lipid levels verified by nuclear magnetic resonance, and
      further weight loss with a lipid-neutral effect may persist for up to 52 weeks.

PMID- 14601691
TI  - Ordering blood for the wrong patient--getting inside the minds of ordering
      physicians.
AB  - OBJECTIVE: To assess the impact on ordering errors when physicians stopped
      handwriting patient identifiers on requests for blood transfusion. MATERIAL AND
      METHODS: Physicians, frustrated by the amount of time required to complete paper
      forms to order blood, asked if the requirement for handwritten patient
      identifiers, which were in addition to such information "stamped" on blood
      requests, could be eliminated. We acquiesced to the request, modified the blood
      ordering forms accordingly, and continued to monitor ordering errors. RESULTS:
      After elimination of the handwritten identifiers in 1997, ordering errors
      increased from an annual rate of 1 in 10,000 to 6 in 10,000 blood requests by
      late 1999. We alerted the clinicians by newsletter, and the rate decreased
      somewhat (3 in 10,000 requests). However, the error rate did not decrease to its
      previous level of 1 in 10,000 requests until mid-2001, about 2 1/2 years after
      reinstitution of the requirement for handwritten patient identifiers. CONCLUSION:
      An obligatory second entry of demographic identifiers on a blood order requires
      ordering physicians to carefully consider the identity of the patient receiving a
      transfusion and reduces the likelihood of transfusion of an unintended recipient.
      Error management tools, such as a predetermined method for planning, reviewing,
      and documenting all changes, facilitate detection of trends and responses to
      corrective actions.

PMID- 14601692
TI  - Rituximab for immune cytopenia in adults: idiopathic thrombocytopenic purpura,
      autoimmune hemolytic anemia, and Evans syndrome.
AB  - OBJECTIVE: To evaluate the efficacy of rituximab for the treatment of adult
      patients with immune cytopenia, including idiopathic thrombocytopenic purpura
      (ITP), autoimmune hemolytic anemia, and Evans syndrome. PATIENTS AND METHODS: We
      retrospectively reviewed the medical charts of all patients treated with
      rituximab for immune cytopenia at the Mayo Clinic in Rochester, Minn, through
      January 1, 2003. Fourteen patients (median age at first diagnosis, 51 years;
      range, 21-79 years) were identified who received 1 or more treatment courses of
      rituximab for treatment of refractory ITP (12 patients), autoimmune hemolytic
      anemia (AIHA) (5 patients), or both ITP and AIHA (classified as Evans syndrome)
      (4 patients). Data regarding age, diagnosis, date of diagnosis, previous
      treatments, comorbid conditions, blood cell counts before taking rituximab,
      number of rituximab treatments, and response to treatment were extracted and
      analyzed. RESULTS: Of 12 patients treated for ITP, 6 were receiving
      corticosteroid-based treatment either alone or combined with other
      immunosuppressive therapy at the time they received rituximab. Complete remission
      occurred in 5 (42%) of 12 patients with ITP and in 2 (40%) of 5 patients with
      AIHA. Response to rituximab in patients with Evans syndrome was seen in either
      ITP or AIHA, but not both. Complete response was often durable in ITP. Responses
      were seen in both splenectomized and nonsplenectomized patients. CONCLUSIONS: Our
      findings, considered with the results of other studies, suggest that rituximab
      deserves early consideration as salvage therapy for immune cytopenias that are
      refractory to both corticosteroid treatment and splenectomy. This series
      represents the largest series of adult patients with AIHA and Evans syndrome.

PMID- 14601693
TI  - Clinical spectrum and laboratory characteristics associated with detection of
      herpes simplex virus DNA in cerebrospinal fluid.
AB  - OBJECTIVE: To determine the clinical, neurologic, and laboratory characteristics
      of patients with herpes simplex virus (HSV) type 1 (HSV-1) or HSV type 2 (HSV-2)
      DNA detected in cerebrospinal fluid (CSF) with use of polymerase chain reaction.
      PATIENTS AND METHODS: Clinical, laboratory, and demographic data were determined
      from 249 CSF specimens (collected from 247 patients >10 years of age) that tested
      positive for HSV-1 or HSV-2 DNA at the Mayo Clinic from January 1999 to August
      2000. RESULTS: The median age of the 200 patients whose age was available was 70
      years vs 40 years for those with HSV-1 or HSV-2 DNA in CSF, respectively.
      Detailed data were available for 39 and 78 patients with positive polymerase
      chain reaction results for HSV-1 and HSV-2, respectively. Of those with HSV-1 DNA
      detected in CSF, 89% had encephalitis, whereas most patients with HSV-2 DNA
      detected in CSF had findings compatible with meningitis. Only 5 (7%) of 69
      patients in whom HSV-2 was detected in CSF had genital lesions at presentation,
      and none of the assessable patients with HSV-2 who had recurrent meningitis had
      active genital lesions at presentation. CONCLUSION: The vast majority (82%) of
      patients with HSV-2 detected in CSF had no history of genital herpes and no
      lesions at the time of presentation. Polymerase chain reaction assays designed to
      detect HSV in CSF should detect HSV-1 and HSV-2 and differentiate between HSV-1
      and HSV-2.

PMID- 14601694
TI  - Provider satisfaction in clinical encounters with ethnic immigrant patients.
AB  - OBJECTIVE: To determine whether physicians' satisfaction in clinical encounters
      with ethnic immigrant patients differs from satisfaction in clinical encounters
      with white patients in the local community. PATIENTS AND METHODS: Postvisit
      assessments from primary care physicians were collected for matched pairs of
      ethnic and control patients at the Mayo Clinic in Rochester, Minn, during a 10
      week study (April 2-June 9, 2001). Ethnic patients were defined as first
      generation Somalian, Cambodian, and Hispanic immigrants. Control patients were
      American-born white patients who were seen by the same physician and matched to
      the ethnic patients in age, sex, and type of visit. T tests and Hotelling T2
      tests were used to analyze differences in physician responses between groups;
      regression analysis was used to identify the relationship between physicians'
      satisfaction and ethnicity in the presence of covariates. RESULTS: Physicians
      were considerably less satisfied with ethnic patient visits compared with control
      patient visits. Larger differences in satisfaction were reported in the areas of
      patient efforts with disease prevention and management of chronic diseases.
      Smaller differences in satisfaction were reported for issues related to
      communication and cultural beliefs and practices. These differences persisted
      after controlling for patient demographics, physician, and visit characteristics.
      CONCLUSIONS: Patients' ethnicity affects physician satisfaction with clinical
      encounters, particularly in the delivery of preventive care and chronic disease
      management.

PMID- 14601695
TI  - Clinical, magnetic resonance imaging, and electroencephalographic findings in
      paraneoplastic limbic encephalitis.
AB  - OBJECTIVE: To analyze clinical presentation of and paraclinical test
      abnormalities in patients with paraneoplastic limbic encephalitis (PLE). PATIENTS
      AND METHODS: We retrospectively reviewed 24 patients seen at the Mayo Clinic in
      Rochester, Minn, between 1985 and 2002 in whom PLE was suspected. Patients were
      identified on the basis of clinical history and presence of cancer. Data were
      reviewed from magnetic resonance imaging (MRI), cerebrospinal fluid (CSF)
      analysis, electroencephalography (EEG), and paraneoplastic serologic studies.
      RESULTS: Common manifestations were cognitive dysfunction (92%), seizures (58%),
      and psychiatric symptoms (50%); 13 patients had small cell lung carcinoma; 11 had
      other malignancies. Paraneoplastic neuronal autoantibodies were found in 14 (64%)
      of 22 patients tested. Electroencephalography showed focal or generalized slowing
      and/or epileptiform activity, maximal in the temporal regions, in all 22 patients
      tested. Magnetic resonance imaging revealed increased T2 signal involving one or
      both temporal lobes in 15 (83%) of 18 patients. Cerebrospinal fluid test results
      were abnormal in 18 (78%) of 23 patients tested. Clinical or radiographic
      evidence of extralimbic involvement was documented in 12 (55%) of 22 patients. No
      abnormality on EEG, MRI, or CSF analysis correlated with a specific cancer type
      or with a specific paraneoplastic autoantibody. CONCLUSIONS: In patients with
      suspected PLE, EEG is invaluable for confirming cerebral dysfunction. Magnetic
      resonance imaging can show unequivocal involvement of temporolimbic structures
      and helps exclude other diagnoses. When EEG and cranial MRI are both normal, PLE
      is unlikely. Comprehensive testing for paraneoplastic neuronal nuclear,
      cytoplasmic, and ion channel autoantibodies is an important part of the
      evaluation, but negative results do not rule out PLE.

PMID- 14601696
TI  - Primer on medical genomics. Part X: Gene therapy.
AB  - Gene therapy is defined as any therapeutic procedure in which genes are
      intentionally introduced into human somatic cells. Both preclinical and clinical
      gene therapy research have been progressing rapidly during the past 15 years;
      gene therapy is now a highly promising new modality for the treatment of numerous
      human disorders. Since the first clinical test of gene therapy in 1989, more than
      600 gene therapy protocols have been approved, and more than 3000 patients have
      received gene therapy. However, at the time of writing this article, no gene
      therapy products have been approved for clinical use. This article explains the
      potential clinical scope of gene therapy and the underlying pharmacological
      principles, describes some of the major gene transfer systems (or vectors) that
      are used to deliver genes to their target sites, and discusses the various
      strategies for controlling expression of therapeutic transgenes. Safety issues
      regarding clinical use of gene therapy are explored, and the most important
      technical challenges facing this field of research are highlighted. This review
      should serve as an introduction to the subject of gene therapy for clinician
      investigators, physicians and medical scientists in training, practicing
      clinicians, and other students of medicine.

PMID- 14601697
TI  - Rational use of D-dimer measurement to exclude acute venous thromboembolic
      disease.
AB  - Clinical diagnosis of venous thromboembolic (VTE) disease is often inaccurate
      because signs and symptoms are nonspecific. Testing for the absence of D-dimer
      levels in the blood of patients with suspected deep venous thrombosis and
      pulmonary embolism can assist in ruling out these illnesses. Some highly
      sensitive D-dimer assays have sufficient specificity to assist in the exclusion
      of VTE disease. Numerous clinical management trials using D-dimer measurement in
      association with additional diagnostic tests have shown that it is safe to
      withhold anticoagulant therapy in selected patients with suspected VTE disease
      who have negative D-dimer assay results. Applying these diagnostic strategies can
      potentially decrease the need for radiological testing. The simplicity of
      measuring D-dimer levels creates the potential for misuse. For safe patient
      management, clinicians must understand the indications for and limitations of D
      dimer measurement in the diagnosis of VTE disease.

PMID- 14601698
TI  - Continuation of medically necessary aspirin and warfarin during cutaneous
      surgery.
AB  - Excisional cutaneous surgery is performed commonly in patients who take medically
      necessary aspirin or warfarin. Although controversy has existed regarding the
      appropriate perioperative management of anticoagulant therapy during cutaneous
      surgery, recent data suggest that the risk of severe hemorrhagic complications is
      not increased if these medications are continued. Brief perioperative
      discontinuation does not lower this already minimal hemorrhagic risk.
      Furthermore, life-threatening thromboembolic complications have been related
      temporally to perioperative discontinuation of both aspirin and warfarin. In
      light of the absence of benefit and the presence of risks associated with
      discontinuation of warfarin and aspirin perioperatively during excisional
      cutaneous surgery, continuation of these medications is recommended in most
      situations. In all cases, the individual patient's medical history and risk
      factors should be taken into account when making this clinical decision, and
      deviation from the guidelines should be considered if clinical imperatives
      warrant.

PMID- 14601699
TI  - Use of opioids in the treatment of severe pain in terminally ill patients--dying
      should not be painful.
AB  - Pain is a common symptom at the end of life. The vast majority of pain can be
      readily managed if simple principles of practice are followed. Chronic pain
      requires continuous analgesia, and severe pain requires use of strong analgesics,
      most commonly the opioids. In addition to drugs administered continually, short
      acting medications must be available for "breakthrough" pain. This article
      reviews the principles of pain management in terminally ill patients, using a
      case-based demonstration.

PMID- 14601700
TI  - 66-year-old man with long-standing intermittent chest pain.

PMID- 14601701
TI  - Ocular ethambutol toxicity.
AB  - Ethambutol is an antimicrobial agent used frequently to treat tuberculosis. The
      most commonly recognized toxic effect of ethambutol is optic neuropathy, which
      generally is considered uncommon and reversible in medical literature. We
      describe a 43-year-old man who developed signs and symptoms of bilateral optic
      neuropathy during treatment with ethambutol. This case and a review of the
      literature show the severe and unpredictable nature of ethambutol toxicity and
      its potential for irreversible vision loss despite careful ophthalmologic
      monitoring.

PMID- 14601702
TI  - Bilateral cytomegalovirus retinitis in a patient with systemic lupus
      erythematosus and end-stage renal disease.
AB  - Rheumatic diseases are not commonly associated with cytomegalovirus (CMV)
      retinitis. We report a case of bilateral CMV retinitis in a human
      immunodeficiency virus-seronegative patient with systemic lupus erythematosus
      (SLE) who was undergoing hemodialysis for end-stage renal disease. The CMV
      retinitis in this patient was associated with combined azathioprine and low-dose
      corticosteroid therapy for lupus flare. This association may have important
      clinical implications because this drug combination is used routinely to treat
      active SLE. Our patient responded to discontinuation of azathioprine, reduction
      of the corticosteroid dose, and systemic administration of ganciclovir. We
      recommend that clinicians maintain heightened awareness of the possibility of CMV
      retinitis in patients with SLE and end-stage renal disease who are receiving
      azathioprine and low-dose corticosteroids.

PMID- 14601703
TI  - Sebastian platelet syndrome: a hereditary macrothrombocytopenia.
AB  - Sebastian platelet syndrome is a rare autosomal dominant disorder characterized
      by macrothrombocytopenia with granulocyte inclusions similar to those in patients
      with Fechtner platelet syndrome but without evidence of hereditary nephritis and
      sensorineural hearing loss that characterizes the latter. Although by light
      microscopy the granulocyte inclusions in these disorders appear morphologically
      similar to those found in May-Hegglin anomaly, another autosomal dominant
      macrothrombocytopenia, by electron microscopy the inclusions are distinct.
      Studies of platelet function usually suggest normal or near-normal platelet
      function, although mild bleeding symptoms can be associated with each of these
      disorders. We describe a 38-year-old woman and her 11-year-old daughter who
      presented with lifelong histories of mild thrombocytopenia and easy bruising.
      Detailed hemostatic studies showed prolonged bleeding times in the child and the
      mother, with the child having absent secondary wave platelet aggregation
      responses to epinephrine, also reflected by testing with the platelet function
      analyzer (PFA-100 device). The mother's hemostatic studies were normal including
      platelet aggregometry, PFA-100 testing, and platelet flow cytometry. By light
      microscopy the blood smears of both individuals showed neutrophil inclusions, and
      their platelets were mildly enlarged but were not giant. Electron microscopy
      showed the neutrophil inclusions seen in classic Sebastian platelet syndrome or
      Fechtner platelet syndrome. These 2 cases expand the description of Sebastian
      platelet syndrome to include individuals with large but not giant platelets and
      mild or minimal thrombocytopenia. The differential diagnosis of hereditary
      thrombocytopenias is reviewed briefly.

PMID- 14601704
TI  - Evaluation and management of geriatric depression in primary care.
AB  - Geriatric depression is a common but frequently unrecognized or inadequately
      treated condition in the elderly population. Manifestations of major depression
      in elderly persons may hinder early detection; anxiety, somatic complaints,
      cognitive impairment, and concurrent medical and neurologic disorders are more
      frequent. Like major depression, minor depression, which is often ignored,
      produces morbidity for elderly persons. Both major and minor depression are
      associated with high mortality rates if left untreated. This article reviews the
      important aspects of geriatric depression for the nonpsychiatric clinician: the
      etiology of depressive conditions in the elderly population, the unique clinical
      features of depression in older people, important evaluation considerations in a
      population with many medical and neurologic comorbidities, and the
      nonpharmacological and pharmacological treatment options for managing depression
      in the geriatric population.

PMID- 14601705
TI  - Importance of assessing musculoskeletal disease in older women.

PMID- 14601706
TI  - Metastatic breast carcinoma mimicking macronodular cirrhosis.

PMID- 14601707
TI  - Acute myocarditis associated with tetanus vaccination.

PMID- 14601708
TI  - Urinothorax: unexpected cause of a pleural effusion.

PMID- 14601709
TI  - Paul Berg--American Nobel Laureate.

PMID- 14601710
TI  - The epidemiology of critical illness in the elderly.
AB  - A substantial proportion of patients admitted to intensive care units (ICUs) are
      elderly patients. Based upon population growth, patient preference, and current
      physician practice, the number of elderly patients who receive critical care
      services is likely to increase substantially over the next 10 to 20 years.
      Numerous studies have shown that survival from critical illness is lower in
      elderly patients; however, after adjusting for factors such as illness severity,
      comorbid diseases, and functional status, chronologic age accounts for very
      little explanatory power for survival from critical illness. Elderly survivors of
      critical illness often have significant functional limitations, but their
      perceived quality of life is usually better than that of younger survivors of
      critical illness. Elderly patients frequently receive less aggressive care in the
      ICU and probably consume a lower relative proportion of ICU resources than
      younger patients. However, this does not necessarily result in worse outcomes.

PMID- 14601711
TI  - Culture, demographics, and critical care issues: an overview.
AB  - The population dynamic and the immigration trends in the United States continue
      to challenge health care professionals who each day must serve an increasingly
      diverse population. Today's physicians must not only have a solid background in
      medical sciences but they must also have knowledge of how culture, race, and
      ethnicity impact how patients view and accept traditional Western practices.
      Whether doctors and patients are close in the "context spectrum" will often
      determine their ability to communicate beyond the spoken language. According to a
      report of the American Medical Association, by the year 2000, out of a total
      812,770 physicians, only 2.5% were Black, 3.5% Hispanic, and 8.9% Asian. Only a
      fraction of a percent was American Native/Alaskan Native. Therefore, the majority
      of the physicians are Caucasian, and it could be assumed that they would likely
      be accustomed to high-context communication styles. The gross of the demographic
      changes and population increases in the United States during the past 10 years
      can be attributed to immigration from regions of the world where low-context
      communication styles are prevalent. Such differences between physicians and
      patients can create difficult, tense situations in an already charged atmosphere
      as can be that of a critical care unit.

PMID- 14601712
TI  - Perioperative anesthesia issues in the elderly.
AB  - Surgical procedures on geriatric patients are not always benign, but
      postoperative mortality and morbidity is improving. Optimal care depends on our
      ability to recognize potential risk factors and intervene in a positive manner.
      Not all the data are complete, and we are missing several key randomized trials,
      but investigators have identified many areas for possible intervention.
      Hopefully, in the near future, more concrete recommendations can be given for
      this very large and important topic of perioperative anesthetic issues in the
      elderly.

PMID- 14601713
TI  - Intensive care unit outcomes in elderly cancer patients.
AB  - As the number of elderly patients receiving oncologic therapies increases, the
      need for better outcome predictors for the critically ill elderly with cancer
      increases. Physicians should not view age as an indicator of poor ICU outcome, as
      many elderly patients with cancer will derive the same benefit from intensive
      care as their younger counterparts. Such a gain can be accomplished without
      overuse of valuable resources. Similar prognostic factors that are applied to the
      younger cancer patients should also be applied to the elderly. These parameters,
      in addition to clinical judgment, can be helpful in deciding who will benefit
      from ICU care regardless of age. Oncologists and critical care physicians will
      need to collaborate and change the paradigm of ICU care for the elderly.

PMID- 14601714
TI  - Common cardiovascular issues encountered in geriatric critical care.
AB  - The incidence and prevalence of CV disease is high in the growing US elderly
      population. It is common for CV disease to be either the primary or secondary
      problem for elderly patients receiving critical care. The therapeutic options for
      CV problems experienced in the critical care setting range from medical
      management with the goal of symptom relief and comfort care to invasive therapies
      such as PCI, intraaortic balloon pump therapy, invasive monitoring, and cardiac
      surgery. Age alone is not a contraindication for any of the invasive therapies.
      Instead, a careful risk-benefit analysis should be performed for each individual
      patient, taking into consideration physiologic age, comorbid conditions, other
      disabilities, and an assessment of quality of life. Additionally, the goals
      (symptom relief, improvement of quality of life, survival benefit) of any therapy
      should be clearly established for individual patients. End-of-life issues,
      cardiovascular surgery, and the disabling of ICDs deserve special consideration
      in the elderly, as these are often challenging issues that will likely be more
      frequently encountered in critical care settings as science and technology
      advance.

PMID- 14601715
TI  - Acute lung injury and the acute respiratory distress syndrome.
AB  - Although ALI/ARDS mortality rates have improved over the last several decades,
      they remain high, particularly in the geriatric patient population. Although
      considerable progress has been made in understanding the pathogenesis of the
      disease, a large number of promising treatments have proven unsuccessful. One
      exception has been in the area of ventilator management, where a strategy of
      protective ventilation with low tidal volumes has demonstrated a significant
      mortality benefit. Basic research continues to help advance our understanding of
      this complex syndrome and identify interesting new directions of investigation.
      The results of several large, randomized trials of new ventilatory and
      pharmacologic strategies currently underway may help identify successful methods
      of treating this important disease.

PMID- 14601716
TI  - Chronic obstructive pulmonary disease in geriatric critical care.
AB  - COPD is a progressive disorder that is punctuated in its later stages with acute
      exacerbations that present a risk for respiratory failure. COPD has a
      disproportionate impact on older patients. In the ICU, therapy is directed toward
      unloading fatigued respiratory muscles, treating airway infection, and
      prescribing bronchodilatory drugs. Most patients survive hospitalization in the
      ICU for an episode of respiratory failure. The severity of the underlying lung
      disease, however, underlies the poor outcomes of patients in terms of
      postdischarge survival and quality of life.

PMID- 14601717
TI  - Community-acquired pneumonia in the elderly.
AB  - CAP is traditionally considered a medical disease, and is managed with
      intravenous fluids and antibiotics on medical floors. Recent cost-containment
      efforts have shifted the provision of care to the outpatient settings, and only
      those with most severe disease and multiple comorbid illnesses are admitted to
      hospitals. Therefore, the proportion of hospitalized patients with severe CAP
      that need intensive care and life support is increasing. Furthermore, the
      incidence of severe CAP is also rising due to disproportionate growth of the
      elderly population that is most vulnerable to this deadly disease. Many of these
      elderly patients have advanced underlying diseases, and CAP might often be a
      terminal event superimposed on an underlying chronic debilitating illness. As ICU
      physicians, we need to be familiar with this disease, its complications, and its
      prognosis to provide intensive care in a timely and rational fashion in some
      patients, and refrain from life support in others. Just as prior efforts have
      sought to improve and standardize criteria for hospital admission, future efforts
      should aim to improve and standardize decisions regarding intensive care and life
      support in these very sick elderly patients. Future efforts in the management of
      CAP need to consider the postdischarge period where most deaths occur. Prevention
      is an important issue especially for those at high risk for CAP.

PMID- 14601718
TI  - Pain in the older adult in the intensive care unit.
AB  - Effective pain management of the older adult begins with pain assessment using
      the proper tools. Understanding the complexities of the older adult in the ICU is
      the first step; this can be done by integrating the evidence-based practice
      guidelines provided by the American Geriatrics Society, the Joint Commission on
      Accreditation of Health Care Organizations (JCAHO pain standards:
      www.jcaho.org/standard/pm_hap.html), and the Society of Critical Care Medicine
      into physicians' and nurses' practice. Joint Commission on Accreditation of
      Health Care Organizations now recommends considering pain as the "fifth vital
      sign" (JCAHO pain standards: www.jcaho.org/standard/pm_hap.html). In summary,
      Park et al highlight key concepts that must be considered for all effective
      treatment plans: "anticipation, recognition, quantification, treatment and
      reassessment of the needs of the patient." Only then can we anticipate the
      impacts of chronic and critical illnesses and realize reliable and superior
      comfort for the elderly.

PMID- 14601719
TI  - Delirium, depression, and anxiety.
AB  - Patients who are critically ill often develop a variety of psychiatric symptoms,
      which require assessment and treatment. The most common psychiatric disorder in
      the intensive care unit is delirium. Depressed mood and anxiety also occur, at
      times as discrete disorders, but more often secondary to delirium. Patients with
      severe mental illnesses, such as schizophrenia and bipolar affective disorder,
      also may become critically ill--assessment and management of these patients often
      requires specialized psychiatric care and is not addressed here.

PMID- 14601720
TI  - End-of-life care in the critically ill geriatric population.
AB  - As the geriatric population in the United States increases and better management
      of chronic diseases improves survival, more elderly will become critically ill
      and potentially require treatment in an intensive care unit (ICU). Dan Callahan
      has written, "... we will live longer lives, be better sustained by medical care,
      in return for which our deaths in old age are more likely to be drawn out and
      wild." Although no health care provider hopes for a drawn out and wild death for
      elderly patients, many geriatric persons will succumb to disease and die after
      having chosen and received ICU care. Recent data suggest that, on average, 11% of
      Medicare recipients spend more that 7 days in the ICU within 6 months before
      death.

PMID- 14601721
TI  - Controversial issues in critical care for the elderly: a perspective from Canada.
AB  - Age alone does not at all preclude the possibility of warranted, effective, and
      successful intensive care. From a medical perspective, the key issue is the
      reversibility or otherwise of an acute illness and where this illness sits in the
      trajectory of that individual's life and possible death. It makes no more sense
      to admit a 19-year-old let alone a 91-year-old to an intensive care unit if
      intensive care cannot provide what is needed. Of paramount importance in our
      consideration of critical care for the elderly is a determination and an
      understanding of the many needs--medical, emotional, social, spiritual,
      psychologic--that elderly people have. By exploring them with compassion and
      sensitivity, we can establish whether the goals of care include critical care and
      the associated technology, or whether alternative and more conservative
      approaches more closely reflect the values and preferences of an increasingly
      elderly population.

PMID- 14601722
TI  - Possible maternal inheritance of breast muscle morphology in turkeys at sixteen
      weeks of age.
AB  - During the study of inheritance of breast muscle morphology of turkeys during
      embryonic development and posthatch in two experiments, interesting results were
      obtained at 16 wk of age. In experiment 1, an experimental line (F) selected long
      term for increased 16-wk BW was crossed reciprocally with a commercial sire line
      (B). Samples of pectoralis major muscle were obtained from three males and three
      females of each genetic group. The F line was reciprocally crossed with a
      randombred control line (RBC2) in experiment 2, and p. major muscle samples were
      taken from 10 males and 10 females of each genetic group. The RBC2 line was the
      base population for the F line. The muscle samples were obtained in a manner to
      avoid contraction. After fixing, the muscle samples were stained with hematoxylin
      and eosin to view muscle morphology. Distinct morphological types were observed
      in the muscle samples for the B, F, and RBC2 lines. The pectoralis major muscle
      from the B line was, in general, characterized by large fibers with a well
      defined extracellular matrix (perimysial and endomysial spaces). Similar to the B
      line, representative samples of the RBC2 line had a well-defined extracellular
      matrix but muscle fiber size was not as large as that of the B line.
      Representative samples of the F line were characterized by a greatly reduced
      extracellular matrix with the muscle fibers not well defined. For the reciprocal
      crosses in both experiments, representative samples indicated the offspring had
      breast muscle morphology similar to that of the female parent, suggesting
      maternal inheritance. There was no sex effect on breast muscle morphology in
      either experiment. In order to study the consistency of the results, muscle
      morphology of representative sections of muscle were subjectively rated by four
      individuals. The ratings ranged from 1 (little extracellar matrix and indistinct
      muscle fibers) to 5 (large extracellular space and distinct muscle fibers).
      Ratings of 2 to 4 were intermediate to these extremes. In experiment 1, ratings
      of the pure B line and the F sire x B dam cross were similar and higher than that
      of the pure F line and B sire x F dam cross, which did not differ in average
      rating. The results for experiment 2 were similar to those for experiment 1 in
      that the average ratings of the reciprocal crosses were similar to that of the
      female parental line. The results from the ratings support maternal inheritance
      of breast muscle morphology.

PMID- 14601723
TI  - Identification of three single nucleotide polymorphisms in the chicken insulin
      like growth factor 1 and 2 genes and their associations with growth and feeding
      traits.
AB  - The chicken insulin-like growth factor (IGF)1 and IGF2 genes have been partially
      sequenced in six individuals of each of two chicken strains of the Black
      Penedesenca breed (PN and MN). These two strains are genetically diverse for
      growth traits. Sequence alignment revealed the existence of three single
      nucleotide polymorphisms (SNP) (IGF1-SNP1, IGF2-SNP2, and IGF2-SNP3). These three
      SNP and a fourth IGF1 polymorphism (IGF1-SNP4) were typed in 60 individuals from
      each strain by using PCR-RFLP or primer extension analysis. No significant
      associations among these four SNP, growth traits, and plasma IGF1 concentration
      were identified. In contrast, suggestive associations (P < or = 0.05) were found
      between IGF1-SNP1 and average daily gain at 107 d and feed efficiency at 44, 73,
      and 107 d. However, these associations were not simultaneously found in both
      strains suggesting that they might have been produced by linkage disequilibrium
      with another mutation located in the IGF1 locus or another linked gene. Since the
      PN and MN strains differ very markedly on their feed intake, the chicken leptin
      gene was included in the sequence analysis. Unfortunately, attempts to amplify
      several regions of this gene were unsuccessful. Even when primers complementary
      to highly conserved regions were used, the PCR consistently failed. Other authors
      have reported similar problems when trying to amplify avian leptin sequences.

PMID- 14601724
TI  - Sequence analysis of bone morphogenetic protein receptor type II mRNA from
      ascitic and nonascitic commercial broilers.
AB  - Ascites syndrome, also known as pulmonary hypertension syndrome (PHS), is a
      common metabolic disorder in rapidly growing meat-type chickens. Environmental
      factors, such as cold, altitude, and diet, play significant roles in development
      of the disease, but there is also an important genetic component to PHS
      susceptibility. The human disease familial primary pulmonary hypertension (FPPH)
      is similar to PHS in broilers both genetically and physiologically. Several
      recent studies have shown that mutations in the bone morphogenetic protein
      receptor type II (BMPR2) gene are a cause of FPPH in humans. To determine whether
      mutations in the chicken BMPR2 gene play a similar role in PHS susceptibility,
      BMPR-II mRNA from ascitic and nonascitic commercial broilers were sequenced and
      compared with the published Leghorn chicken BMPR-II mRNA sequence. Fourteen
      single nucleotide polymorphisms (SNP) were identified in the commercial broiler
      BMPR-II mRNA. No mutations unique to ascites-susceptible broilers were present in
      the coding, 5' untranslated or 3' untranslated regions of BMPR-II mRNA. The
      twelve SNP present within the coding region of BMPR-II mRNA were synonymous
      substitutions and did not alter the BMPR-II protein sequence. In addition,
      analysis of BMPR2 gene expression by reverse transcriptase-PCR indicated that
      there were no differences in BMPR-II mRNA levels in ascitic and nonascitic birds.
      Therefore, it appears unlikely that mutations in the BMPR2 gene were responsible
      for susceptibility to PHS in these commercial broilers.

PMID- 14601725
TI  - Growth, livability, and feed conversion of 1957 versus 2001 broilers when fed
      representative 1957 and 2001 broiler diets.
AB  - Body weight, feed consumption, and mortality were measured in the 1957 Athens
      Canadian Randombred Control (ACRBC) strain and in the 2001 Ross 308 strain of
      broilers when fed representative 1957 and 2001 diets. The dietary regimens were
      chosen to be representative of those used in the industry in 1957 vs. 2001. The
      1957 diets were fed as mash, the 2001 starter was as crumbles, and the grower and
      finisher diets were pellets. Feed consumption and BW were recorded at 21, 42, 56,
      70, and 84 d of age to cover the two broiler strains normal span of marketing
      ages. Mortality was low, and the mortality of the ACRBC was approximately half
      that of the modem strain. Average BW for the ACRBC on the 1957 diets were 176,
      539,809, 1,117, and 1,430 g vs. 743, 2,672, 3,946, 4,808, and 5,520 g for the
      Ross 308 on the 2001 diets at 21, 42, 56, 70, and 84 d of age, respectively. The
      42-d feed conversion (FC) on the 2001 and 1957 feeds for the Ross 308 were 1.62
      and 1.92 with average BW of 2,672 and 2,126 g and for the ACRBC were 2.14 and
      2.34 with average BW of 578 and 539 g, respectively. The Ross 308 broiler on the
      2001 feed was estimated to have reached 1,815 g BW at 32 d of age with a FC of
      1.47, whereas the ACRBC on the 1957 feed would not have reached that BW until 101
      d of age with a FC of 4.42.

PMID- 14601726
TI  - Carcass composition and yield of 1957 versus 2001 broilers when fed
      representative 1957 and 2001 broiler diets.
AB  - The yield of carcass parts as well as levels of carcass fat, moisture, and ash
      were measured in the 1957 Athens-Canadian Randombred Control (ACRBC) and in the
      Ross 308 commercial broiler, when fed diets that were representative of those
      being fed during 1957 and 2001. The Ross 308 was used to represent 2001
      commercial broilers. Comparisons of carcass weights of the Ross 308 on the 2001
      diet versus the ACRBC on the 1957 diet showed they were 6.0, 5.9, 5.2, and 4.6
      times heavier than the ACRBC at 43, 57, 71, and 85 d of age, respectively. Yields
      of hot carcass without giblets (fat pad included) were 12.3, 13.6, 12.2, and 11.1
      percentage points higher for the Ross 308 than for the ACRBC at those ages. The
      yields of total breast meat for the Ross 308 were 20.0, 21.3, 21.9, and 22.2% and
      were 8.4, 9.9, 10.3, and 9.8 percentage points higher than for the ACRBC at those
      ages. Yields of saddle and legs for the Ross 308 broiler were approximately 31 to
      32% over the four ages and were about 1.5 to 2% higher than for the ACRBC at the
      different ages. The Ross 308 averaged 13.7, 15.0, 18.6, and 18.5% whole carcass
      fat versus 8.5, 10.6, 12.7, and 14.0% for the ACRBC at the four ages. In
      conjunction with previous studies, the current data show that yield of broiler
      carcass parts has continued to increase over time and that genetics has been the
      major contributor to changes in yield.

PMID- 14601727
TI  - A comparison of the immune response of a 2001 commercial broiler with a 1957
      randombred broiler strain when fed representative 1957 and 2001 broiler diets.
AB  - Immunocompetence of the 2001 Ross 308 broiler strain and the 1957 Athens Canadian
      Randombred Control (ACRBC) strain was compared when they were given diets
      representative of those that were being used in 1957 and 2001. Antibody response
      against SRBC, in vivo lymphoproliferation against Phytohemagglutinin-P (PHA-P),
      and inflammatory and phagocytic responses of the macrophages were measured. The
      Ross 308 strain on the 2001 diet had higher BW at 24 d of age (P = 0.0001),
      whereas the ACRBC had greater lymphoid organ weights (except thymus) relative to
      BW (P < or = 0.003). The ACRBC strain showed greater antibody responses against
      SRBC than the 2001 Ross 308 birds for much of the trial (P < or = 0.0362).
      However, the Ross 308 broilers had greater PHA-P-induced toe-web swelling
      response (P < or = 0.0129). Inflammatory exudate cell numbers were higher in the
      Ross 308 broilers than in the ACRBC birds (P = 0.0261). The percentage of
      macrophages that phagocytized SRBC was comparable between the two strains, but
      the number of SRBC phagocytized by individual macrophages was higher (P = 0.0122)
      in the Ross 308 broiler than in the ACRBC chickens. Nitrite production by
      macrophages following lipopolysacharide stimulation was comparable between the
      two strains. Interactions of diet, strain, and sex were inconsistent among all
      parameters tested. In conclusion, the current study suggested that genetic
      selection for improved broiler performance has resulted in a decrease in the
      adaptive arm of the immune response but an increase in the cell-mediated and
      inflammatory responses.

PMID- 14601728
TI  - Is ribosomal capacity a potential metabolic marker of muscle development?
      Measurement by muscular biopsy.
AB  - Metabolic markers of muscle metabolism could help geneticists and nutritionists
      predict the breast meat development of chickens. The aim of the current study was
      to test the ribosomal capacity (CS), a potential metabolic marker, and to
      evaluate a simple biopsy method on the pectoralis major muscle. Ribosomal
      capacity was measured in three commercial meat chicken genotypes differing in
      their growth rate. Fast-, medium-, and slow-growing male chickens were fed using
      three commercial dietary programs of increasing energy and protein concentration
      (nine treatments). Biopsy was performed at 4 wk of age on the p. major 12
      chickens per treatment. Fast-, medium-, and slow-growing chickens were
      slaughtered at market weight, i.e., 6, 8, and 12 wk of age, respectively, and
      breast meat (right and left p. major + minor) was dissected. A significant
      reduction in BW at slaughter (-1 to -3%) and breast meat yield (-4%) occurred
      only in biopsied medium-growing chickens but not in the other two types. Slow
      growing chickens had a significantly lower CS (8.75 microg/mg) than the two other
      chicken types (9.40 and 9.46 microg/mg for fast- and medium-growing chickens,
      respectively). No significant dietary effect or interaction of dietary treatment
      with genotype was measured. The CS was not significantly correlated to breast
      meat development. Under conditions of the present experiment, CS may not be a
      relevant marker of subsequent breast meat development at 4 wk of age. The biopsy
      technique can easily be applied to other markers.

PMID- 14601729
TI  - An evaluation of different growth functions for describing the profile of live
      weight with time (age) in meat and egg strains of chicken.
AB  - A total of 86 profiles from meat and egg strains of chickens (male and female)
      were used in this study. Different flexible growth functions were evaluated with
      regard to their ability to describe the relationship between live weight and age
      and were compared with the Gompertz and logistic equations, which have a fixed
      point of inflection. Six growth functions were used: Gompertz, logistic, Lopez,
      Richards, France, and von Bertalanffy. A comparative analysis was carried out
      based on model behavior and statistical performance. The results of this study
      confirmed the initial concern about the limitation of a fixed point of
      inflection, such as in the Gompertz equation. Therefore, consideration of
      flexible growth functions as an alternatives to the simpler equations (with a
      fixed point of inflection) for describing the relationship between live weight
      and age are recommended for the following reasons: they are easy to fit, they
      very often give a closer fit to data points because of their flexibility and
      therefore a smaller RSS value, than the simpler models, and they encompasses
      simpler models for the addition of an extra parameter, which is especially
      important when the behavior of a particular data set is not defined previously.

PMID- 14601730
TI  - Total and water-soluble phosphorus in broiler litter over three flocks with alum
      litter treatment and dietary inclusion of high available phosphorus corn and
      phytase supplementation.
AB  - Three pen trials were conducted to determine the main effect of alum addition to
      litter on form of poultry litter P using a 2 x 2 factorial structure of the
      subunit treatments: diets including high available phosphorus/low phytate corn
      (HAPC) and phytase (PHYT). Male broilers (1,760 per flock) were grown to 42 d
      having starter diets with 0.45% available P and grower diets with 0.35% available
      P. In the first trial, total litter P (tP) was greatest for the yellow dent corn
      (YDC) diet (12 g/kg) and least for the HAPC and PHYT combination (H&P) diet (6.9
      g/kg) with the individual PHYT and HAPC diets falling in between at 9.1 g/kg and
      9.4 g/kg tP. Also in the first trial, the litter water-soluble P (wP) was highest
      for PHYT (2.8 g/kg), least for the HAPC and H&P diets (1.5 g/kg) with the YDC
      diet falling between (2.2 g/kg). Alum was added to the litter after the first
      experiment. In the second and third experiments, alum inclusion significantly
      reduced the wP when compared with the treatments with no alum. In the third
      trial, the least wP was present in the alum-HAPC treatment. Phytase, YDC, and
      HAPC diets with no alum litter treatment generated the most wP. Since these diets
      appear to have little or no difference with respect to quantity of wP, this work
      suggests that form of litter P generated by alternative diets should be
      considered as criteria when attempting to reduce P in broiler litter applied to
      land.

PMID- 14601731
TI  - Graded atmospheric oxygen level effects on performance and ascites incidence in
      broilers.
AB  - The effects of graded atmospheric O2 concentration (12, 14, 16, 18, and 20.6%) on
      chick performance and propensity to develop ascites were investigated using
      commercial male broilers. Chicks were housed in calorimetry chambers for 2 wk
      with incoming air diluted with N to provide the desired O2 concentration at
      thermoneutral (TN) ambient temperature. Day 14 body weight, weight gain, feed
      consumption, and gain-to-feed ratio increased (P < 0.01) as O2 concentration
      incrementally rose from 12 to 20.6%. Body weight was 138 g for the lowest
      atmospheric O2 level compared to 371 g for 20.6% O2. The greatest treatment
      difference occurred between the 12 and 14% O2 concentrations. Growth depression
      appeared related to feed consumption. Ascites heart ratio (AHR), ascites score
      (AS), right ventricular mass (RVM), and hematocrit (HCT) all increased (P < 0.01)
      as O2 concentration decreased. Blood HCT appeared to be a more sensitive
      indicator of physiological change attributable to atmospheric O2 than AHR, AS, or
      RVM. The data reported herein suggests that 19.6% atmospheric O2 is the minimal
      allowable level for housing birds within a relatively stress-free, TN environment
      to avoid cardiac and HCT changes related to ascites.

PMID- 14601732
TI  - Production of an egg yolk antibody specific to microbial uricase and its
      inhibitory effects on uricase activity.
AB  - Ammonia gas produced from poultry manure can be a potential source of
      environmental pollution. Microbial uricase in poultry manure is an important
      target enzyme to reduce ammonia production because ammonia is mainly generated
      from the microbial decomposition of uric acid in the manure. Thus, the inhibition
      of microbial uricase is critical in preventing NH3 volatilization. A potential
      method of inhibiting uricase activity is the use of antibodies specific to
      microbial uricase. Therefore, this study was designed to evaluate 1) the
      production of the uricase-specific egg yolk antibody (IgY) from immunized hens
      and 2) the effect of the uricase-specific IgY on the activity of uricase. A total
      of 12 Single Comb White Leghorn hens were injected intramuscularly with uricase
      from Arthrobacter globiformis. The hens were immunized a second and third time at
      1 and 2 wk, respectively, after the initial injection. The production of uricase
      specific IgY was first detected at 2 wk after the initial immunization, and
      levels increased more than threefold at 4 wk. The method including water
      extraction, ammonium sulfate precipitation, and ethanol precipitation showed the
      most acceptable IgY purity and over 97% uricase-specific IgY recovery. Finally,
      the effect of the uricase-specific IgY on uricase activity was determined by a
      uricase assay. The slope ratio showed that the immune-IgY from the uricase
      immunized hens and nonimmune IgY from nonimmunized control hens reduced uricase
      degradation by 58 and 43%, respectively, compared to the uricase treatment. The
      regression slope indicated that the immune IgY and nonimmune IgY treatments had a
      significant inhibitory effects on uricase activity compared to the uricase.

PMID- 14601733
TI  - The role of dietary vitamin E in experimental Listeria monocytogenes infections
      in turkeys.
AB  - The current study was designed to determine if dietary vitamin E influenced
      either the gut clearance or levels of peripheral blood CD4+ and CD8+ T
      lymphocytes in adult turkeys experimentally infected with Listeria monocytogenes.
      Turkeys were fed vitamin E (0, 100, or 200 IU) from day of hatch to time of
      necropsy. After 6 wk on the experimental diet, turkeys were orally inoculated
      with L. monocytogenes (approximately 10(9) cfu). To monitor infection status,
      cloacal swabs were taken on selected days post-inoculation (DPI). At necropsy,
      samples of viscera, including liver, spleen, cecum, duodenum, ileum, and colon
      were collected and cultured for L. monocytogenes. In experiments 1 and 2,
      recovery of L. monocytogenes from cloacal swabs, tissues, and intestines from
      turkeys fed vitamin E was generally lower than that from turkeys fed the control
      diet, although these differences were not statistically significant. When data
      from both trials were combined, L. monocytogenes was cultured less frequently
      from cloacal swabs of the vitamin E-treated group (200 IU) on 2 and 3 DPI, when
      compared to controls (0 IU, P < 0.01). There were no changes in virulence
      characteristics of L. monocytogenes cells, as measured by in vitro killing of Ped
      2E9 cells, recovered from cloacal swabs or tissues of experimentally infected
      turkeys fed the control or a vitamin E treatment diet. Flow cytometric analysis
      indicated that CD4+ and CD8+ peripheral blood T lymphocytes were elevated at 6
      and 8 DPI in infected turkeys given 200 IU vitamin E.

PMID- 14601734
TI  - Immune response to a mucosally administered aflatoxin B1 vaccine.
AB  - In the present study, a mucosal vaccine was used in an effort to elicit serum IgG
      and intestinal secretory IgA against the mycotoxin aflatoxin B1 (AFB) in
      chickens. AFB was coupled to carrier proteins (BSA and porcine thyroglobulin) for
      use as a vaccine and ELISA coating antigen, respectively. Seven-day-old broiler
      chicks were divided into groups of 10 and immunized with one of four vaccine
      preparations: 1) AFB-BSA conjugate alone, 2) AFB-BSA linked to the B subunit of
      the recombinant heat-labile enterotoxin of Escherichia coli (rLT-B), 3) AFB-BSA
      admixed with rLT-B, or 4) AFB-BSA mixed with cholera toxin (CT). Each vaccine
      preparation was administered perorally, intrarectally, or intraperitoneally, with
      a booster immunization given 2 wk later. Sera and feces were collected weekly and
      assayed using isotype specific ELISA. All three routes of immunization elicited
      significant serum IgG responses; however, the intraperitoneal route was strongest
      for all vaccine preparations tested. The serum IgG immune response to the AFB-BSA
      conjugate was enhanced by co-administration of rLT-B but not by covalent coupling
      to rLT-B or coadministration with CT. Secretory IgA anti-CT and anti-rLT-B
      antibodies were detected in fecal supernatants, but no anti-AFB responses could
      be detected. As all 12 treatment groups produced significant levels of serum IgG
      anti-AFB, any of these approaches, including oral administration without
      adjuvant, may afford the chicken some level of protection through simple immuno
      interception of free AFB.

PMID- 14601735
TI  - Leptin and insulin downregulate leptin receptor gene expression in chicken
      derived leghorn male hepatoma cells.
AB  - In chickens, leptin is expressed mainly in the liver, where its receptor gene
      expression has also been reported, and in adipose tissue. In view of the key role
      played by the liver in lipogenesis in avian species, the hepatic expression of
      leptin may have physiological significance. In this study, we showed that leptin
      is constitutively expressed and secreted in a chicken-derived hepatoma cell line
      (LMH). Although insulin regulates leptin expression in vivo, incubation of LMH
      cells in the presence of 100 nM insulin for 24 or 48 h had no effect on leptin
      expression or its secretion in the culture medium. In addition, we developed a
      specific chicken leptin receptor real-time reverse transcription (RT)-PCR, and
      downregulation of leptin receptor gene expression by homologous and heterologous
      signals was demonstrated, as relative leptin receptor mRNA levels were
      significantly decreased after exposure of LMH cells to recombinant chicken leptin
      or porcine insulin. In conclusion, our results indicate that leptin is probably
      able to desensitize its own response in the chicken liver. Finally, the ability
      of insulin and leptin to regulate chicken leptin receptor gene expression
      suggests a direct role of leptin in the control of hepatic metabolism.

PMID- 14601736
TI  - Effects of different levels of zinc on the performance and immunocompetence of
      broilers under heat stress.
AB  - Male broilers were used to evaluate the effect of zinc on performance and immune
      competence during heat stress (HS). Broilers raised in either a thermoneutral
      (TN, 23.9 degrees C constant) or HS (23.9 to 35 degrees C cycling) environment
      were fed a low zinc diet (LZ; 34 mg/kg), an adequate zinc diet (AZ; 68 mg/kg), or
      a supplemental zinc diet (HZ; 181 mg/kg). Humoral immunity was assessed by
      intravenous injection of 7% SRBC followed by evaluation of serum for antibody
      titers in primary and secondary responses. Cell-mediated immunity was assessed
      using a Sephadex stimulation method to recruit abdominal exudate cells (AEC) to
      evaluate macrophage phagocytic ability. The HS birds consumed 12.5% less feed,
      gained 24.6% less weight, and had lower feed efficiency when compared to TN
      birds. Dietary zinc levels did not impact growth performance or plasma zinc
      concentration. Numbers of AEC, macrophages in AEC, phagocytic macrophages, and
      internalized opsonized and unopsonized SRBC were increased by HZ. Total, IgM, and
      IgG antibody titers for primary and secondary responses were significantly
      increased in birds receiving HZ under TN conditions. Tibia zinc concentration
      increased with increasing zinc levels but did not change with temperature.
      Lymphoid organ weights, primary and secondary antibody responses, incidences of
      macrophages in AEC, phagocytic ability of macrophages, and plasma zinc
      concentration were all significantly reduced by HS. These results indicate that
      the immune response of broilers can be influenced by the level of zinc in the
      diet and by environmental conditions.

PMID- 14601737
TI  - Guar meal germ and hull fractions differently affect growth performance and
      intestinal viscosity of broiler chickens.
AB  - High concentrations of guar meal in poultry diets deleteriously affect growth,
      feed intake, and digesta viscosity. These effects are attributed to residual gum
      in the meal. A 2 x 5 factorial experiment investigated the impacts of two guar
      meal fractions (germ and hull) at five inclusion levels (0, 2.5, 5.0, 7.5, and
      10.0%) on intestinal viscosity, measures of growth, and feed conversion in
      broiler chickens fed to 20 d of age. Growth and feed conversion ratio were not
      affected by inclusion of as much as 7.5% of the germ fraction into poultry diets,
      while inclusion of the hull fraction reduced growth at all concentrations. The
      hull fraction increased intestinal viscosity at all inclusion levels fed,
      although feed conversion was not affected until the inclusion rate exceeded 5.0%.
      The germ fraction significantly increased intestinal viscosity at 7.5 and 10%
      inclusion rates. When germ fraction was fed, relative organ weights remained
      constant through all concentrations except for the ventriculus and duodenum at
      7.5 and 10% inclusion levels. Relative pancreas weight was significantly
      increased at the 10% level of the hull fraction. Increases in intestinal
      viscosity corresponded with growth depression. These results suggest that
      residual gum was responsible for some deleterious effects seen when guar meal was
      fed. The germ fraction was a superior ingredient when compared with the hull
      fraction. The guar meal germ fraction constituting as much as 7.5% of the diet
      supported growth and feed conversion measures similar to those observed with a
      typical corn-soybean poultry ration.

PMID- 14601738
TI  - Impact of galactose, lactose, and Grobiotic-B70 on growth performance and energy
      utilization when fed to broiler chicks.
AB  - Three chick assays were conducted to determine the effect of increasing dietary
      galactose (GAL), lactose (LAC), and Grobiotic-B70, a LAC fermentation product, on
      growth performance, toxicity, and energy utilization when fed to commercial
      broiler chicks. One-day-old male commercial broiler chicks were randomly assigned
      to treatments in each assay. In all assays, a 22% CP corn-soybean meal-dextrose
      basal diet containing a growth-promoting antibiotic (Bacitracin methylene
      disalicylate) was fed. In assay 1, GAL was added at 2, 4, 6, 10, or 15%. In assay
      2, Grobiotic-B70 was added at 5%. In assay 3, GAL, LAC, and Grobiotic-B70 were
      each added at 2, 4, and 6%. All additions were made in place of dextrose, and
      diets were fed from 0 to 20 or 21 d of age. In assay 1, the 15% GAL treatment
      resulted in high mortality (27%) by d 3 and was terminated. The 10% GAL treatment
      also resulted in increased mortality, most of which occurred during the 7-to-14-d
      period. Inclusion of 2 and 4% GAL resulted in an improvement (P < 0.05) in growth
      compared to the basal diet. Inclusion of 2, 4, 6, and 10% GAL resulted in a
      significant linear decrease in MEn (r2 = 0.85). In chick assay 2, 5% Grobiotic
      B70 increased growth during the first 2 wk. In chick assay 3, 6% Grobiotic
      increased weight gain (P < 0.05) from 0 to 14 d, and addition of 2 or 4% GAL, 2
      or 4% LAC, and 4 or 6% Grobiotic-B70 increased weight gain (P < 0.08) from 0 to
      21 d. Our results indicate that levels of 10 to 15% GAL are toxic. In contrast,
      low levels of GAL and Grobiotic-B70, and possibly LAC, may increase growth of
      commercial broiler chicks.

PMID- 14601739
TI  - Lysine needs of summer-reared male broilers from six to eight weeks of age.
AB  - Experimentation was conducted to estimate dietary lysine needed to optimize
      production of summer-reared broilers between 42 to 56 d of age. Male Ross x Ross
      308 chicks were placed in floor pens of an open-sided house and provided common
      feeds from placement to 42 d of age. During the subsequent 42 to 56 d, birds
      received a corn-soybean meal basal diet (18% CP and 3,250 kcal/kg ME) established
      to provide limiting essential amino acids favorably balanced near requirement
      levels with the exception of lysine. Four 0.10% increments of L-lysine
      isonitrogenously displaced L-glutamic acid from the basal diet to provide
      analyzed values progressing from 0.85 to 1.25%. Body weight gain and mortality
      were not altered as dietary lysine increased; however, feed conversion linearly
      improved. Chilled carcass yield, amount of abdominal fat, and recovery of
      skinless boneless breast meats were not affected. Measurements on nitrogen
      balance and plasma levels of total protein, albumin, glucose, and uric acid taken
      at 49 d from a concurrent study using sample birds in raised-wire cages and
      identical feeds also failed to define a requirement. However, plasma aspartic
      transferase increased to a maximum approximating 1.05% lysine, whereas free
      lysine concentration linearly increased to the highest level. Overall data
      supported a lysine requirement no less than 0.95% that was greater than the
      previous minimum of 0.85% obtained under similar terms without heat stress.
      Suppression of growth from heat stress appears to reduce the absolute need for
      lysine; however, increased dietary concentration appears necessary to accommodate
      depressed feed intake and improve its effectiveness.

PMID- 14601740
TI  - In vitro fermentation characteristics of two mushroom species, an herb, and their
      polysaccharide fractions, using chicken cecal contents as inoculum.
AB  - In vitro fermentabilities of two mushrooms (Lentinus edodes--LenS; Tremella
      fuciformis--TreS), an herb (Astragalus membranaceus--AstS), and their
      polysaccharide fractions (LenE, TreE, and AstE) were investigated using
      microflora from chicken ceca. Polysaccharides were extracted using the hot water
      method. The mushrooms had lower polysaccharide yields (8 to 10%) than the herb
      (31%). Fermentation kinetics were determined using the in vitro cumulative gas
      production technique. End-products, such as gas, volatile fatty acids (VFA), and
      ammonia, were also determined. The gas profiles of intact materials were similar
      for AstS and LenS. The TreS had a diphasic digestion pattern. The extracts had
      similar profiles to the intact materials though gas production rates were faster.
      Intact materials tended to produce less VFA than the extracts though LenS and
      AstE had the highest total VFA production overall. Intact materials contained
      more protein than the extracts, and therefore resulted in more branched-chain
      fatty acids and ammonia. Fermentation kinetics and end-point products
      demonstrated differences in availability of substrates between the mushrooms and
      herb. These medicinal mushroom and herb materials, particularly their
      polysaccharide extracts, show promise in altering microbial activities and
      composition in chicken ceca. In vivo experiments are necessary for confirmation
      of this hypothesis.

PMID- 14601741
TI  - Interrelationship between environmental temperature and dietary nonphytate
      phosphorus in chicks.
AB  - Four levels of nonphytate P (NPP; 0.2, 0.3, 0.4, and 0.5%; total P = 0.46, 0.56,
      0.66, and 0.76%) and two temperatures (25 and 37 degrees C) were evaluated in
      chicks from 8 to 22 d. In experiment 1, crossbred male chicks (New Hampshire x
      Columbian) housed at 25 degrees C increased weight gain at all increasing NPP
      levels, but chicks exposed to 37 degrees C did not show increased weight gain
      beyond 0.3% NPP. In experiment 2, environmental temperature was not increased
      until d 15. Weight gain of crossbred male chicks fed the 0.2% NPP diet was
      similar at both temperatures, but chicks exposed to 37 degrees C had lower weight
      gains than chicks housed at 25 degrees C for all other NPP levels. On d 22 to 24,
      chicks that had been housed at 25 degrees C and fed 0.2, 0.3, and 0.5% NPP were
      moved to the 37 degrees C chamber to evaluate heat stress on older chicks. Chicks
      fed the 0.2% NPP diet showed 35% mortality within 6 h. In experiment 3, both male
      commercial (Ross x Ross) and crossbred chicks that had been housed at 25 degrees
      C and fed 0.2% NPP from 8 to 22 d showed increased signs of severe heat distress
      when exposed to 37 degrees C on d 22. Our results suggest that the NPP
      requirement for growth of 8-to-22-d-old chicks may be reduced by high
      temperature. However, a NPP deficiency may result in increased mortality or
      severe heat distress in older chicks that are exposed to an acute increase in
      temperature.

PMID- 14601742
TI  - Estrogen receptor-alpha populations change with age in commercial laying hens.
AB  - Older hens in production lay larger but fewer eggs than younger birds, and the
      incidence of soft and broken shells is greater in older hens than younger. These
      changes are attributable at least in part to changing hormone profiles and
      diminished ability of the hen to transport calcium at the duodenum. In further
      exploration of this relationship, a study was conducted with three ages of Hy
      Line W-36 birds: prelay pullets (PL; 19 wk, 0% production), peak-production hens
      (PP; 29 wk, approximately 93% production), and late-stage hens (LS; 71 wk,
      approximately 80% production). Hens from the PP and LS groups were palpated for
      presence of an egg in the shell gland; hens were then euthanized and tissues
      (kidney, shell gland, hypothalamus) were removed for quantification of estrogen
      receptor-alpha (ERalpha) populations via immunocytochemical and Western blot
      analyses. Localization of ERalpha by immunostaining in the shell gland showed
      differences among age groups; however, no differences were noted in localization
      of ERalpha between age groups in the kidney and hypothalamus. In both the kidney
      and the shell gland there was a decrease in the amount of ERalpha, as detected by
      immunoblotting, in the LS hens compared to PL and PP birds (P < 0.05). The
      results suggest that failure of calcium regulating mechanisms with age may be
      mediated at least in part through the reduced populations of estrogen receptors
      in certain critical tissues.

PMID- 14601743
TI  - Effects of F-strain Mycoplasma gallisepticum inoculation on serum very low
      density lipoprotein diameter and fractionation of cholesterol among lipoproteins
      in commercial egg-laying hens.
AB  - Experimental inoculation with the F-strain of Mycoplasma gallisepticum (FMG) at
      12 wk of age has been shown to affect the performance, liver, reproductive
      organs, and yolk lipid characteristics of commercial layers. Therefore, this
      study was conducted to determine the serum lipoprotein characteristics of
      commercial egg-laying hens at 16 wk of age and throughout lay after inoculation
      with FMG at 12 wk of age. Mean diameters of very low density lipoproteins (VLDL)
      were determined for the 10th, 50th, and 90th percentiles of serum total VLDL of
      each hen. Percentages of total serum cholesterol recovered in VLDL and low and
      high density lipoprotein particle classes were also determined. Inoculation of
      birds with FMG at 12 wk did not change the physical properties or relative
      concentrations of their circulating lipoproteins. However, the age of the bird
      had significant differential effects on all the parameters examined. These data
      demonstrate that FMG-inoculation at 12 wk of age does not affect the lipoproteins
      of laying hens, but because these birds were housed in biological isolation
      units, these results do not preclude the possibility that these yolk precursors
      may be affected in FMG-infected birds that are housed in facilities in which
      there are increased levels of environmental stress. These data further suggest
      that alterations in liver, reproductive organs, and yolk lipid characteristics in
      response to FMG, as noted in previous reports on commercial layers, are not
      mediated through changes in circulating VLDL diameters.

PMID- 14601744
TI  - Changes in the population of pituitary protein transcription factor-1 nuclei in
      the anterior pituitary during withdrawal and resumption of feeding in hens.
AB  - Pituitary protein transcription factor (Pit-1) is a member of a large family of
      protein transcription factors that include Pit-1, Oct-1, Oct-2, and Unc-86. The
      goal of this experiment was to determine whether the population of Pit-1
      containing cells changes in the anterior pituitary of chicken by the regulation
      of feeding. White Leghorn hens were subjected to withdrawal and resumption of
      feeding. The anterior pituitaries were collected from hens at pretreatment, at 2
      d after withdrawal of feeding (2DWF), and 1 d and 5 d after resumption of feeding
      (1DRF and 5DRF, respectively). Sections of the pituitaries were immunostained for
      Pit-1. They were examined under a light microscope with an image analysis
      computer system. The Pit-1 positive nuclei were found in the glandular cells in
      the cephalic and caudal lobes of the anterior pituitary in all four groups of
      hens. The Pit-1 cell population significantly increased in the 2DWF and 1DRF and
      decreased thereafter in 5DRF. These results suggests that feed withdrawal may
      stimulate Pit-1 expression in chicken, suggesting that Pit-1 may be involved in
      control of pituitary functions during the process of feed regulation.

PMID- 14601745
TI  - Bacterial recovery from breast skin of genetically feathered and featherless
      broiler carcasses immediately following scalding and picking.
AB  - Genetically feathered and featherless sibling broilers selected for matched BW
      were killed, scalded, and defeathered to determine the consequences of feathers
      and empty feather follicles on the recovery of bacteria from carcass breast skin.
      In trial 1, the vents of all carcasses were plugged and sutured before scalding
      to prevent the expulsion of cloacal contents during picking. In trial 2, half of
      the carcasses had their vents plugged and sutured. Immediately after
      defeathering, breast skin was aseptically removed, and bacteria associated with
      it were enumerated. In trial 1, the levels of bacteria recovered did not differ
      between feathered and featherless carcasses: Campylobacter log10 1.4 cfu/mL of
      rinse, coliform log10 1.8, Escherichia coli log10 1.6, and total aerobic bacteria
      log10 3.1. In trial 2, the carcasses that had vents plugged and sutured had lower
      levels of all four types of bacteria (differences of Campylobacter log10 0.7
      cfu/mL, coliform log10 1.8, E. coli log10 1.7, and total aerobic bacteria log10
      0.5) than those carcasses with open vents. The lower levels of bacteria recovered
      from carcasses with the vents plugged and sutured during picking enabled
      detection of small but significant differences between feathered and featherless
      carcasses. The level of coliform and E. coli recovered was slightly higher by
      log10 0.7 cfu for feathered carcasses, but featherless carcasses had marginally
      higher levels of total aerobic bacteria by log10 0.4 cfu. Feathered and
      featherless carcasses with open vents during picking did not differ in the levels
      of recovery of coliform, E. coli, and total aerobic bacteria from breast skin.

PMID- 14601746
TI  - Breast muscle development in commercial broiler chickens.
AB  - Genetic and gender-related variations in breast muscle yield of broiler chickens
      may be attributed to differences in number and size of muscle cells (myofibers).
      In this study, male and female broilers from eight commercial strain crosses (SC)
      were compared for body and breast muscle weight with adjustment of the Gompertz
      function. Additionally, breast fillet dimensions (length, width, and depth) and
      myofiber density (myofiber number/area; MFD) were assessed. Live weight and
      breast muscle development was determined to 56 d of age at weekly intervals. MFD
      was assessed at 8 d of age. As expected, SC differed in BW, breast weight and
      yield, and breast fillet dimensions and had variations in growth curves. Maximal
      growth rate for breast weight was reached approximately 4 d after that of BW.
      Males and females showed different growth curves, with males having slower growth
      rate maturity parameter and reaching the maximal growth rate later than females
      for BW and breast weight. Breast depth was the breast measure with highest
      positive correlation to breast yield. SC differences could not be explained by
      MFD, but males had higher MFD density than females. The possible relationship of
      the MFD observations to total myofiber number is discussed.

PMID- 14601747
TI  - Estimating vaccine effects on transmission of infection from household outbreak
      data.
AB  - This article is concerned with a method for making inferences about various
      measures of vaccine efficacy. These measures describe reductions in
      susceptibility and in the potential to transmit infection. The method uses data
      on household outbreaks; it is based on a model that allows for transmission of
      infection both from within a household and from the outside. The use of household
      data is motivated by the hope that these are informative about vaccine-induced
      reduction of the potential to transmit infection, as household outbreaks contain
      some information about the possible source of infection. For illustration, the
      method is applied to observed data on household outbreaks of smallpox. These data
      are of the form needed and the number of households is of a size that can be
      managed in a vaccine trial. It is found that vaccine effects, such as the mean
      reduction in susceptibility and the mean reduction in the potential to infect
      others, per infectious contact, can be estimated with precision. However, a more
      specific parameter reflecting the reduction in infectivity for individuals
      partially responding to vaccination is not estimated well in the application. An
      evaluation of the method using artificial data shows that this parameter can be
      estimated with greater precision when we have outbreak data on a large number of
      small households.

PMID- 14601748
TI  - Bayesian shrinkage estimation of the relative abundance of mRNA transcripts using
      SAGE.
AB  - Serial analysis of gene expression (SAGE) is a technology for quantifying gene
      expression in biological tissue that yields count data that can be modeled by a
      multinomial distribution with two characteristics: skewness in the relative
      frequencies and small sample size relative to the dimension. As a result of these
      characteristics, a given SAGE sample may fail to capture a large number of
      expressed mRNA species present in the tissue. Empirical estimators of mRNA
      species' relative abundance effectively ignore these missing species, and as a
      result tend to overestimate the abundance of the scarce observed species
      comprising a vast majority of the total. We have developed a new Bayesian
      estimation procedure that quantifies our prior information about these
      characteristics, yielding a nonlinear shrinkage estimator with efficiency
      advantages over the MLE. Our prior is mixture of Dirichlets, whereby species are
      stochastically partitioned into abundant and scarce classes, each with its own
      multivariate prior. Simulation studies reveal our estimator has lower integrated
      mean squared error (IMSE) than the MLE for the SAGE scenarios simulated, and
      yields relative abundance profiles closer in Euclidean distance to the truth for
      all samples simulated. We apply our method to a SAGE library of normal colon
      tissue, and discuss its implications for assessing differential expression.

PMID- 14601749
TI  - Dose-finding with two agents in Phase I oncology trials.
AB  - We propose an adaptive two-stage Bayesian design for finding one or more
      acceptable dose combinations of two cytotoxic agents used together in a Phase I
      clinical trial. The method requires that each of the two agents has been studied
      previously as a single agent, which is almost invariably the case in practice. A
      parametric model is assumed for the probability of toxicity as a function of the
      two doses. Informative priors for parameters characterizing the single-agent
      toxicity probability curves are either elicited from the physician(s) planning
      the trial or obtained from historical data, and vague priors are assumed for
      parameters characterizing two-agent interactions. A method for eliciting the
      single-agent parameter priors is described. The design is applied to a trial of
      gemcitabine and cyclophosphamide, and a simulation study is presented.

PMID- 14601750
TI  - Nonparametric comparison of two survival-time distributions in the presence of
      dependent censoring.
AB  - When testing the null hypothesis that treatment arm-specific survival-time
      distributions are equal, the log-rank test is asymptotically valid when the
      distribution of time to censoring is conditionally independent of randomized
      treatment group given survival time. We introduce a test of the null hypothesis
      for use when the distribution of time to censoring depends on treatment group and
      survival time. This test does not make any assumptions regarding independence of
      censoring time and survival time. Asymptotic validity of this test only requires
      a consistent estimate of the conditional probability that the survival event is
      observed given both treatment group and that the survival event occurred before
      the time of analysis. However, by not making unverifiable assumptions about the
      data-generating mechanism, there exists a set of possible values of corresponding
      sample-mean estimates of these probabilities that are consistent with the
      observed data. Over this subset of the unit square, the proposed test can be
      calculated and a rejection region identified. A decision on the null that
      considers uncertainty because of censoring that may depend on treatment group and
      survival time can then be directly made. We also present a generalized log-rank
      test that enables us to provide conditions under which the ordinary log-rank test
      is asymptotically valid. This generalized test can also be used for testing the
      null hypothesis when the distribution of censoring depends on treatment group and
      survival time. However, use of this test requires semiparametric modeling
      assumptions. A simulation study and an example using a recent AIDS clinical trial
      are provided.

PMID- 14601751
TI  - Estimating the accuracy of polymerase chain reaction-based tests using endpoint
      dilution.
AB  - Polymerase chain reaction (PCR)-based tests for various microorganisms or target
      DNA sequences are generally acknowledged to be highly "sensitive," yet the
      concept of sensitivity is ill-defined in the literature on these tests. We
      propose that sensitivity should be expressed as a function of the number of
      target DNA molecules in the sample (or specificity, when the target number is 0).
      However, estimating this "sensitivity curve" is problematic, since it is
      difficult to construct samples with a fixed number of targets. Nonetheless, using
      serially diluted replicate aliquots of a known concentration of the target DNA
      sequence, we show that it is possible to disentangle random variations in the
      number of target DNA molecules from the underlying test sensitivity. We develop
      parametric, nonparametric, and semiparametric (spline-based) models for the
      sensitivity curve. The methods are compared on a new test for M. genitalium.

PMID- 14601752
TI  - Abundance estimation of diving animals by the double-platform line transect
      method.
AB  - In conventional line transect theory, it is assumed that all animals on the line
      are detected. This article introduces an extended and generalized hazard
      probability model without the need for such an assumption. The proposed method
      needs a survey design with independent observers having the same visual region
      and assumes an explicit distinction of simultaneous and delayed duplicates. It
      can take account of random heterogeneity caused by surfacing behavior as well as
      systematic heterogeneity by covariate effects. Furthermore, it can be easily
      extended to cases in which data from incompletely independent observers are
      available. The abundance estimate is based on the Horvitz-Thompson estimator in
      unequal detectability sampling scheme. Simulation studies suggest that the
      proposed method has good performance. The method is applied to a real data set on
      Antarctic minke whales in the illustration.

PMID- 14601753
TI  - A Bayesian approach for joint modeling of cluster size and subunit-specific
      outcomes.
AB  - In applications that involve clustered data, such as longitudinal studies and
      developmental toxicity experiments, the number of subunits within a cluster is
      often correlated with outcomes measured on the individual subunits. Analyses that
      ignore this dependency can produce biased inferences. This article proposes a
      Bayesian framework for jointly modeling cluster size and multiple categorical and
      continuous outcomes measured on each subunit. We use a continuation ratio probit
      model for the cluster size and underlying normal regression models for each of
      the subunit-specific outcomes. Dependency between cluster size and the different
      outcomes is accommodated through a latent variable structure. The form of the
      model facilitates posterior computation via a simple and computationally
      efficient Gibbs sampler. The approach is illustrated with an application to
      developmental toxicity data, and other applications, to joint modeling of
      longitudinal and event time data, are discussed.

PMID- 14601754
TI  - Sensitivity analysis for the assessment of causal vaccine effects on viral load
      in HIV vaccine trials.
AB  - Vaccines with limited ability to prevent HIV infection may positively impact the
      HIV/AIDS pandemic by preventing secondary transmission and disease in vaccine
      recipients who become infected. To evaluate the impact of vaccination on
      secondary transmission and disease, efficacy trials assess vaccine effects on HIV
      viral load and other surrogate endpoints measured after infection. A standard
      test that compares the distribution of viral load between the infected subgroups
      of vaccine and placebo recipients does not assess a causal effect of vaccine,
      because the comparison groups are selected after randomization. To address this
      problem, we formulate clinically relevant causal estimands using the principal
      stratification framework developed by Frangakis and Rubin (2002, Biometrics 58,
      21-29), and propose a class of logistic selection bias models whose members
      identify the estimands. Given a selection model in the class, procedures are
      developed for testing and estimation of the causal effect of vaccination on viral
      load in the principal stratum of subjects who would be infected regardless of
      randomization assignment. We show how the procedures can be used for a
      sensitivity analysis that quantifies how the causal effect of vaccination varies
      with the presumed magnitude of selection bias.

PMID- 14601755
TI  - Identification of differentially expressed genes in high-density oligonucleotide
      arrays accounting for the quantification limits of the technology.
AB  - In DNA microarray analysis, there is often interest in isolating a few genes that
      best discriminate between tissue types. This is especially important in cancer,
      where different clinicopathologic groups are known to vary in their outcomes and
      response to therapy. The identification of a small subset of gene expression
      patterns distinctive for tumor subtypes can help design treatment strategies and
      improve diagnosis. Toward this goal, we propose a methodology for the analysis of
      high-density oligonucleotide arrays. The gene expression measures are modeled as
      censored data to account for the quantification limits of the technology, and two
      gene selection criteria based on contrasts from an analysis of covariance
      (ANCOVA) model are presented. The model is formulated in a hierarchical Bayesian
      framework, which in addition to making the fit of the model straightforward and
      computationally efficient, allows us to borrow strength across genes. The
      elicitation of hierarchical priors, as well as issues related to parameter
      identifiability and posterior propriety, are discussed in detail. We examine the
      performance of our proposed method on simulated data, then present a detailed
      case study of an endometrial cancer dataset.

PMID- 14601756
TI  - Estimation of spontaneous mutation rates.
AB  - Spontaneous or randomly occurring mutations play a key role in cancer
      progression. Estimation of the mutation rate of cancer cells can provide useful
      information about the disease. To ascertain these mutation rates, we need
      mathematical models that describe the distribution of mutant cells. In this
      investigation, we develop a discrete time stochastic model for a mutational birth
      process. We assume that mutations occur concurrently with mitosis so that when a
      nonmutant parent cell splits into two progeny, one of these daughter cells could
      carry a mutation. We propose an estimator for the mutation rate and investigate
      its statistical properties via theory and simulations. A salient feature of this
      estimator is the ease with which it can be computed. The methods developed herein
      are applied to a human colorectal cancer cell line and compared to existing
      continuous time models.

PMID- 14601757
TI  - Models for yeast prions.
AB  - The cytoplasmic heritable determinant [PSI+] of the yeast Saccharomyces
      cerevisiae exhibits prion-like properties. The properties of yeast prions are
      studied in the hope that this will enhance the understanding of mammalian prions,
      which cause mad-cow, Creutzfeldt-Jakob, and related neurodegenerative diseases.
      When host cells divide, the yeast prions distribute themselves without loss over
      the daughter cells. Experimental data provide information on how the proportion
      of cells with prions decreases over time when priori replication is inhibited.
      One feature of scientific interest is the unknown mean number, n0, of prions
      assumed to be present in the cells at the start of the experiment. We develop
      several stochastic models and by fitting them to the data, we obtain
      substantially larger estimates of n0 compared with a previous analysis. An
      interesting feature of a model with constant cell generation times is that the
      predicted proportion of cells with prions varies over time as a sequence of
      linked hyperbolic curves. Avenues for future research are outlined, which relax
      simplifying assumptions made in the models. We make several recommendations for
      the design of future experiments.

PMID- 14601758
TI  - Hazard regression for interval-censored data with penalized spline.
AB  - This article introduces a new approach for estimating the hazard function for
      possibly interval- and right-censored survival data. We weakly parameterize the
      log-hazard function with a piecewise-linear spline and provide a smoothed
      estimate of the hazard function by maximizing the penalized likelihood through a
      mixed model-based approach. We also provide a method to estimate the amount of
      smoothing from the data. We illustrate our approach with two well-known interval
      censored data sets. Extensive numerical studies are conducted to evaluate the
      efficacy of the new procedure.

PMID- 14601759
TI  - A new method for choosing sample size for confidence interval-based inferences.
AB  - Scientists often need to test hypotheses and construct corresponding confidence
      intervals. In designing a study to test a particular null hypothesis, traditional
      methods lead to a sample size large enough to provide sufficient statistical
      power. In contrast, traditional methods based on constructing a confidence
      interval lead to a sample size likely to control the width of the interval. With
      either approach, a sample size so large as to waste resources or introduce
      ethical concerns is undesirable. This work was motivated by the concern that
      existing sample size methods often make it difficult for scientists to achieve
      their actual goals. We focus on situations which involve a fixed, unknown scalar
      parameter representing the true state of nature. The width of the confidence
      interval is defined as the difference between the (random) upper and lower
      bounds. An event width is said to occur if the observed confidence interval width
      is less than a fixed constant chosen a priori. An event validity is said to occur
      if the parameter of interest is contained between the observed upper and lower
      confidence interval bounds. An event rejection is said to occur if the confidence
      interval excludes the null value of the parameter. In our opinion, scientists
      often implicitly seek to have all three occur: width, validity, and rejection.
      New results illustrate that neglecting rejection or width (and less so validity)
      often provides a sample size with a low probability of the simultaneous
      occurrence of all three events. We recommend considering all three events
      simultaneously when choosing a criterion for determining a sample size. We
      provide new theoretical results for any scalar (mean) parameter in a general
      linear model with Gaussian errors and fixed predictors. Convenient computational
      forms are included, as well as numerical examples to illustrate our methods.

PMID- 14601760
TI  - Bayesian optimal designs for Phase I clinical trials.
AB  - A broad approach to the design of Phase I clinical trials for the efficient
      estimation of the maximum tolerated dose is presented. The method is rooted in
      formal optimal design theory and involves the construction of constrained
      Bayesian c- and D-optimal designs. The imposed constraint incorporates the
      optimal design points and their weights and ensures that the probability that an
      administered dose exceeds the maximum acceptable dose is low. Results relating to
      these constrained designs for log doses on the real line are described and the
      associated equivalence theorem is given. The ideas are extended to more practical
      situations, specifically to those involving discrete doses. In particular, a
      Bayesian sequential optimal design scheme comprising a pilot study on a small
      number of patients followed by the allocation of patients to doses one at a time
      is developed and its properties explored by simulation.

PMID- 14601761
TI  - Generalized additive selection models for the analysis of studies with
      potentially nonignorable missing outcome data.
AB  - Rotnitzky, Robins, and Scharfstein (1998, Journal of the American Statistical
      Association 93, 1321-1339) developed a methodology for conducting sensitivity
      analysis of studies in which longitudinal outcome data are subject to potentially
      nonignorable missingness. In their approach, they specify a class of fully
      parametric selection models, indexed by a non- or weakly identified selection
      bias function that indicates the degree to which missingness depends on
      potentially unobservable outcomes. Estimation of the parameters of interest
      proceeds by varying the selection bias function over a range considered plausible
      by subject-matter experts. In this article, we focus on cross-sectional,
      univariate outcome data and extend their approach to a class of semiparametric
      selection models, using generalized additive restrictions. We propose a
      backfitting algorithm to estimate the parameters of the generalized additive
      selection model. For estimation of the mean outcome, we propose three types of
      estimating functions: simple inverse weighted, doubly robust, and orthogonal. We
      present the results of a data analysis and a simulation study.

PMID- 14601762
TI  - Partial AUC estimation and regression.
AB  - Accurate diagnosis of disease is a critical part of health care. New diagnostic
      and screening tests must be evaluated based on their abilities to discriminate
      diseased from nondiseased states. The partial area under the receiver operating
      characteristic (ROC) curve is a measure of diagnostic test accuracy. We present
      an interpretation of the partial area under the curve (AUC), which gives rise to
      a nonparametric estimator. This estimator is more robust than existing
      estimators, which make parametric assumptions. We show that the robustness is
      gained with only a moderate loss in efficiency. We describe a regression modeling
      framework for making inference about covariate effects on the partial AUC. Such
      models can refine knowledge about test accuracy. Model parameters can be
      estimated using binary regression methods. We use the regression framework to
      compare two prostate-specific antigen biomarkers and to evaluate the dependence
      of biomarker accuracy on the time prior to clinical diagnosis of prostate cancer.

PMID- 14601763
TI  - Sequential conditional probability ratio tests for normalized test statistic on
      information time.
AB  - Sequential conditional probability ratio tests (SCPRTs) provide monitoring
      procedures with a unique property that a decision reached at early stopping is
      unlikely to be reversed should the trial continue to the planned end (Xiong, X.,
      1995, Journal of the American Statistical Association 90, 1463-1473; Tan, M.,
      Xiong, X., and Kutner, M. H., 1998, Biometrics 54, 682-95). It actually provides
      a probability statement of a conclusion reversal, should the proposed interim
      analysis plan be used. To broaden its scope of applications, in this article we
      develop the SCPRT in terms of Brownian motion, which is applicable to most
      clinical trials with various endpoints. In addition, we utilize the unique
      structure of the SCPRT to derive a class of adaptive sequential tests that retain
      the significance level and power in the presence of a nuisance parameter. We
      illustrate the proposed methods with examples in clinical trials.

PMID- 14601764
TI  - Analyzing multiply matched cohort studies with two different comparison groups:
      application to pregnancy rates among HIV+ women.
AB  - We develop a new statistical method to analyze multiply matched cohort studies
      with two different comparison groups. We employ a linear-logistic model to
      describe the underlying log-odds ratios and use a conditional likelihood approach
      to conduct inference. Under the assumption of homogeneous log-odds ratios, we
      provide methods to construct both asymptotic and exact confidence regions of the
      two log-odds ratios in a simple case. We propose a score test to evaluate the
      assumption of homogeneous log-odds ratios across strata. While our methods are
      general, we develop them around a specific application, namely, the study of
      pregnancy rates in HIV-infected women. Our analyses suggest that HIV infection is
      associated with a decrease in pregnancy rates and that this decrease in fertility
      becomes significant after accounting for illicit drug use.

PMID- 14601765
TI  - A spatiotemporal stochastic process model for species spread.
AB  - We use a spatiotemporal Markov process to model the spread of an ecological
      population through its environment over time. Available habitat is divided into
      sites, and a parametric function of spatial variables is used to model the
      probability that one site is colonized from another. This allows us both to make
      predictions about the future spread of a population, and to determine which are
      the important factors governing colonizations. The model evolves in discrete
      time, allowing the population distribution to change seasonally in accordance
      with breeding patterns. Discrete time formulations are natural for ecological
      populations, but are problematic due to difficulties of fitting and predicting
      over irregular time intervals. The model described here can accommodate years of
      missing data and can therefore fit and predict at irregular intervals. Two
      methods of approximating the likelihood are described and applied to
      ornithological survey data for the woodlark, Lullula arborea, from Thetford
      Forest in the U.K.

PMID- 14601766
TI  - Bayesian deconvolution analysis of pulsatile hormone concentration profiles.
AB  - Many hormones are secreted into the circulatory system in a pulsatile manner and
      are cleared exponentially. The most common method of analyzing these systems is
      to deconvolve the hormone concentration into a secretion function and a clearance
      function. Accurate estimation of the model parameters depends on the number and
      location of the secretion pulses. To date, deconvolution analysis assumes the
      number and approximate location of these pulses are known a priori. In this
      article, we present a novel Bayesian approach to deconvolution that jointly
      models the number of pulses along with all other model parameters. Our method
      stochastically searches for the secretion pulses. This is accomplished by viewing
      the set of parameters that define the pulses as a point process. Pulses are
      determined by a birth-death process which is embedded in Markov chain Monte Carlo
      algorithm. This idea originated with Stephens (2000, Annals of Statistics 28, 40
      74) in the context of finite mixture model density estimation, where the number
      of mixture components is unknown. There are several advantages that our model
      enjoys over the traditional frequentist approaches. These advantages are
      highlighted with four datasets consisting of serum concentration levels of
      luteinizing hormone obtained from ovariectomized ewes.

PMID- 14601767
TI  - Parametric modeling of reaction time experiment data.
AB  - A simple parametric model is proposed for data from a point-process version of a
      reaction time experiment. It is used to statistically check for the presence and
      nature of nonlinear inhibition in the eye-brain-hand system, as well as to study
      the nature of the reaction time delay distribution. The model tells us that, in
      principle, the second-order intensity estimate can be used to determine whether
      the experimental subject is systematically observing the first or the second of
      two flashes transmitted in short succession. Nonparametric estimates of second
      order intensity functions are used in conjunction with this model. In particular,
      the model allows for the computation of good bandwidths for intensity curve
      estimation. A parametric bootstrap can also be implemented. Our methods are
      illustrated with 12 runs of data from a real reaction time experiment. It is
      found that nonlinear inhibition is present in the eye-brain-hand system. However,
      there are insufficient data to distinguish between log-normality and normality in
      the reaction time distribution, due partly to confounding with the particular
      kind of nonlinear inhibition present in the system.

PMID- 14601768
TI  - Binomial regression with misclassification.
AB  - Motivated by a study of human papillomavirus infection in women, we present a
      Bayesian binomial regression analysis in which the response is subject to an
      unconstrained misclassification process. Our iterative approach provides
      inferences for the parameters that describe the relationships of the covariates
      with the response and for the misclassification probabilities. Furthermore, our
      approach applies to any meaningful generalized linear model, making model
      selection possible. Finally, it is straightforward to extend it to multinomial
      settings.

PMID- 14601769
TI  - Shrinkage estimation for functional principal component scores with application
      to the population kinetics of plasma folate.
AB  - We present the application of a nonparametric method to performing functional
      principal component analysis for functional curve data that consist of
      measurements of a random trajectory for a sample of subjects. This design
      typically consists of an irregular grid of time points on which repeated
      measurements are taken for a number of subjects. We introduce shrinkage estimates
      for the functional principal component scores that serve as the random effects in
      the model. Scatterplot smoothing methods are used to estimate the mean function
      and covariance surface of this model. We propose improved estimation in the
      neighborhood of and at the diagonal of the covariance surface, where the
      measurement errors are reflected. The presence of additive measurement errors
      motivates shrinkage estimates for the functional principal component scores.
      Shrinkage estimates are developed through best linear prediction and in a
      generalized version, aiming at minimizing one-curve-leave-out prediction error.
      The estimation of individual trajectories combines data obtained from that
      individual as well as all other individuals. We apply our methods to new data
      regarding the analysis of the level of 14C-folate in plasma as a function of time
      since dosing of healthy adults with a small tracer dose of 14C-folic acid. A time
      transformation was incorporated to handle design irregularity concerning the time
      points on which the measurements were taken. The proposed methodology,
      incorporating shrinkage and data-adaptive features, is seen to be well suited for
      describing population kinetics of 14C-folate-specific activity and random
      effects, and can also be applied to other functional data analysis problems.

PMID- 14601770
TI  - Bayesian approaches to joint cure-rate and longitudinal models with applications
      to cancer vaccine trials.
AB  - Complex issues arise when investigating the association between longitudinal
      immunologic measures and time to an event, such as time to relapse, in cancer
      vaccine trials. Unlike many clinical trials, we may encounter patients who are
      cured and no longer susceptible to the time-to-event endpoint. If there are cured
      patients in the population, there is a plateau in the survival function, S(t),
      after sufficient follow-up. If we want to determine the association between the
      longitudinal measure and the time-to-event in the presence of cure, existing
      methods for jointly modeling longitudinal and survival data would be
      inappropriate, since they do not account for the plateau in the survival
      function. The nature of the longitudinal data in cancer vaccine trials is also
      unique, as many patients may not exhibit an immune response to vaccination at
      varying time points throughout the trial. We present a new joint model for
      longitudinal and survival data that accounts both for the possibility that a
      subject is cured and for the unique nature of the longitudinal data. An example
      is presented from a cancer vaccine clinical trial.

PMID- 14601771
TI  - Balancing population size and genetic information in parentage analysis studies.
AB  - In parentage analysis studies, the parameters of interest typically are not the
      parent assignments themselves, but population parameters such as variance in
      fertility, self-pollination rate, or average dispersal distances. The precision
      of parameter estimates is affected by two factors: the number of offspring under
      consideration, and the precision with which the offspring can be assigned to
      parents. When assignment of parents is based on genetic information, the
      confidence in assignments is affected by the number and polymorphism of the loci
      considered, and by the number of potential parents in the population. Studying
      larger populations may yield higher numbers of offspring, but since larger
      populations contain more potential parents, more (or more highly polymorphic)
      loci are necessary to attain a given level of confidence in the parent
      assignments. This article addresses how to relate the size of the population and
      the number of loci when designing a study. It is shown that the number of loci
      needed to assign all offspring unambiguously is proportional to the logarithm of
      the population size. In some cases, the constant of proportionality can be
      determined, eliminating the need for simulation-based projections. Population
      wide measures of uncertainty in parent assignments are also introduced, and it is
      shown that holding uncertainty "steady" as the population size increases also
      requires increasing the number of loci proportional to the logarithm of the
      population size. Data from a study of self-pollination are used to illustrate the
      techniques suggested.

PMID- 14601772
TI  - Incorporating data received after a sequential trial has stopped into the final
      analysis: implementation and comparison of methods.
AB  - In a sequential clinical trial, accrual of data on patients often continues after
      the stopping criterion for the study has been met. This is termed "overrunning."
      Overrunning occurs mainly when the primary response from each patient is measured
      after some extended observation period. The objective of this article is to
      compare two methods of allowing for overrunning. In particular, simulation
      studies are reported that assess the two procedures in terms of how well they
      maintain the intended type I error rate. The effect on power resulting from the
      incorporation of "overrunning data" using the two procedures is evaluated.

PMID- 14601773
TI  - Latent transition regression for mixed outcomes.
AB  - Health status is a complex outcome, often characterized by multiple measures.
      When assessing changes in health status over time, multiple measures are
      typically collected longitudinally. Analytic challenges posed by these
      multivariate longitudinal data are further complicated when the outcomes are
      combinations of continuous, categorical, and count data. To address these
      challenges, we propose a fully Bayesian latent transition regression approach for
      jointly analyzing a mixture of longitudinal outcomes from any distribution.
      Health status is assumed to be a categorical latent variable, and the multiple
      outcomes are treated as surrogate measures of the latent health state, observed
      with error. Using this approach, both baseline latent health state prevalences
      and the probabilities of transitioning between the health states over time are
      modeled as functions of covariates. The observed outcomes are related to the
      latent health states through regression models that include subject-specific
      effects to account for residual correlation among repeated measures over time,
      and covariate effects to account for differential measurement of the latent
      health states. We illustrate our approach with data from a longitudinal study of
      back pain.

PMID- 14601774
TI  - Goodness-of-fit methods for additive-risk models in tumorigenicity experiments.
AB  - In tumorigenicity experiments, a complication is that the time to event is
      generally not observed, so that the time to tumor is subject to interval
      censoring. One of the goals in these studies is to properly model the effect of
      dose on risk. Thus, it is important to have goodness of fit procedures available
      for assessing the model fit. While several estimation procedures have been
      developed for current-status data, relatively little work has been done on model
      checking techniques. In this article, we propose numerical and graphical methods
      for the analysis of current-status data using the additive-risk model, primarily
      focusing on the situation where the monitoring times are dependent. The finite
      sample properties of the proposed methodology are examined through numerical
      studies. The methods are then illustrated with data from a tumorigenicity
      experiment.

PMID- 14601775
TI  - The evidential value in the DNA database search controversy and the two-stain
      problem.
AB  - Does the evidential strength of a DNA match depend on whether the suspect was
      identified through database search or through other evidence ("probable cause")?
      In Balding and Donnelly (1995, Journal of the Royal Statistical Society, Series A
      158, 21-53) and elsewhere, it has been argued that the evidential strength is
      slightly larger in a database search case than in a probable cause case, while
      Stockmarr (1999, Biometrics 55, 671-677) reached the opposite conclusion. Both
      these approaches use likelihood ratios. By making an excursion to a similar
      problem, the two-stain problem, we argue in this article that there are certain
      fundamental difficulties with the use of a likelihood ratio, which can be avoided
      by concentrating on the posterior odds. This approach helps resolving the above
      mentioned conflict.

PMID- 14601776
TI  - An interesting method to detect single or multiple clusters.

PMID- 14601777
TI  - Microbial infections in the twenty first century: a continuous challenge.

PMID- 14601778
TI  - Echinococcosis multilocularis in south-eastern Anatolia, Turkey.
AB  - OBJECTIVE: To quantify the human prevalence, elucidate possible risk factors and
      present other epidemiological parameters of human alveolar echinococcosis in the
      south-eastern region of Turkey. DESIGN: A retrospective study. SETTINGS: South
      eastern region (Anatolia) of Turkey by two medical centres: Dicle University
      Medical Faculty in Diyarbakir and Harran University Medical Faculty in Urfa.
      SUBJECTS: Forty seven cases of human alveolar echinococcosis were presented
      between the period of 1980 and 2000. METHODS: For the majority of our patients,
      personal anamnestic, clinical data and addresses were available from their files,
      and we visited their villages to investigate the risk factors for human alveolar
      echinococcosis. Epidemiological parameters were evaluated. RESULTS: The 47 cases
      consisted of 18 (38.3%) males and 29 (61.7%) females. The average age was 34.6
      years. In all cases, lesions occurred in the liver. No village or district had
      more than one case. The majority of patients (73.8%) were farmers and 33 had a
      history of dog ownership. CONCLUSION: This region has a higher incidence than
      Turkey as a whole, and domestic dogs and free-ranging dogs seem to be the main
      source of infection.

PMID- 14601780
TI  - Traditional remedies in children around Eastern Cape, South Africa.
AB  - OBJECTIVE: To gauge the views of mothers and other caregivers on the use of
      traditional remedies in the community. DESIGN: Descriptive study. SETTING: Five
      health centres affiliated to the UNITRA, Faculty of Health Sciences. METHODS:
      Medical students administered a questionnaire to mothers and other caregivers.
      Areas covered included how commonly traditional remedies are used, experience
      with traditional remedies in children, reasons for use, how administered, and
      problems encountered. RESULTS: There were 103 respondents, 7.8% rated use of
      traditional remedies non-existent, 20.4% rated it as rare and the rest said it
      was common. 57.3% of the respondents had used these remedies in their children,
      and 83.1% of them said they would use them again. Only 20.7% of respondents
      reported problems with these remedies, including diarrhoea, vomiting, fever and
      death. The preparations used were known by only 40.7% of respondents. The
      remedies were administered by the mother and grandmother in 82.8% of cases; and
      were mainly given orally, by enema or by scarification. The amount administered
      varied from spoonful(s) up to 2.5 l. Children of all ages were given traditional
      remedies, usually for diarrhoea, fevers and constipation, or as prophylactics.
      These remedies were used because they are effective, available and safe, or due
      to customary beliefs and pressure from others. CONCLUSION: The use of traditional
      remedies in children is common in communities around Umtata. There is need to
      study the composition and activity profiles of commonly used preparations so as
      to develop appropriate management protocols in case of toxicity.

PMID- 14601779
TI  - Cryptosporidium parvum and Isospora belli infections among patients with and
      without diarrhoea.
AB  - OBJECTIVE: To assess the importance of Cryptosporidium parvum and Isospora belli
      infections as a cause of diarrhoea among patients admitted to the Medical Wards
      in Queen Elizabeth Central Hospital (QECH) in Blantyre, Malawi. DESIGN:
      Prospective case control study. SUBJECTS: One hundred and twenty one patients
      with diarrhoea and 122 patients without diarrhoea. MAIN OUTCOME MEASURES:
      Demonstration of C. parvum and I. belli oocysts by examination of at least one
      stool sample per patient using phenol auramine-O-fluorescence staining and an
      immuno-fluorescent assay with monoclonal antibodies against Cryptosporidium,
      seropositivity for HIV and AIDS. RESULTS: In 22% of the patients with diarrhoea
      an infection with C. parvum or I. belli was found. Thirteen (11%) of them had a
      C. parvum and 14 (12%) an I. belli infection; a mixed infection was found in one
      patient. In the control group, three (3%) C. parvum and three (3%) I. belli
      infections were seen. The prevalence of both infections was very significantly
      higher in the cohort of diarrhoea patients than in the controls, 13/108 versus
      3/119 (p=0.0099) for C. parvum, and 14/107 versus 3/119 (p=0.0056) for I. belli.
      Infections were only seen in HIV positive patients. Two hundred and four (84%)
      patients were HIV positive and 145 (60%) of them had AIDS. CONCLUSIONS: C. parvum
      and I. belli infections are a significant cause of diarrhoea among medical in
      patients at QECH. Examinations of stool specimen for parasites among hospitalised
      patients with diarrhoea provide data for a more appropriate management.

PMID- 14601781
TI  - Quality of glycaemic control in ambulatory diabetics at the out-patient clinic of
      Kenyatta National Hospital, Nairobi.
AB  - BACKGROUND: Treatment of diabetes mellitus is based on the evidence that lowering
      blood glucose as close to normal range as possible is a primary strategy for
      reducing or preventing complications or early mortality from diabetes. This
      suggests poorer glycaemic control would be associated with excess of diabetes
      related morbidity and mortality. This presumption is suspected to reach high
      proportions in developing countries where endemic poverty abets poor glycaemic
      control. There is no study published on Kenyan patients with diabetes mellitus
      about their glycaemic control as an audit of diabetes care. OBJECTIVE: To
      determine the glycaemic control of ambulatory diabetic patients. DESIGN: Cross
      sectional study on each clinic day of a randomly selected sample of both type 1
      and 2 diabetic patients. SETTING: Kenyatta National Hospital. METHODS: Over a
      period of six months, January 1998 to June 1998. During routine diabetes care in
      the clinic, mid morning random blood sugar and glycated haemoglobin (HbA1c) were
      obtained. RESULTS: A total of 305 diabetic patients were included, 52.8% were
      females and 47.2% were males. 58.3% were on Oral Hypoglycaemic Agent (OHA) only,
      22.3% on insulin only; 9.2% on OHA and insulin and 4.6% on diet only. 39.5% had
      mean HbA1c < or = 8% while 60.5% had HbA1c > or = 8%. Patients on diet-only
      therapy had the best mean HbA1c = 7.04% while patients on OHA-only had the worst
      mean HbA1c = 9.06%. This difference was significant (p=0.01). The former group,
      likely, had better endogenous insulin production. The influence of age, gender
      and duration of diabetes on the level of glycaemic control observed did not
      attain statistically significant proportions. CONCLUSION: The majority of
      ambulatory diabetic patients attending the out-patient diabetic clinic had poor
      glycaemic control. The group with the poorest level of glycaemic control were on
      OHA-only, while best control was observed amongst patients on diet-only, because
      of possible fair endogenous insulin production. Poor glycaemic control was
      presumed to be due to sub-optimal medication and deteriorating diabetes. There is
      need to empower patients with knowledge and resources to enhance their individual
      participation in diabetes self-care. Diabetes care providers and facilities also
      need capacity building to improve care of patients with diabetes.

PMID- 14601782
TI  - Use of a modified Alvorado score in the diagnosis of acute appendicitis.
AB  - BACKGROUND: The negative appendicectomy rates have remained high. The integration
      of clinical scores into the diagnostic process in acute appendicitis has had the
      purposes of improving decision making and reducing the negative rates in this
      common condition. The performance of these score systems have however, not been
      uniform. OBJECTIVE: To assess the usefulness of a modified Alvorado score (1986)
      to predict groups of patients with suspected appendicitis for definite surgery,
      observation or discharge from hospital. DESIGN: Prospective study. SETTING:
      Kenyatta National Hospital (KNH), a central referral and teaching hospital in
      Nairobi, Kenya. PATIENTS: One hundred and eighty nine patients with suspected
      acute appendicitis were studied over a period of twelve months. METHODS: Five
      symptoms and four signs were assigned numerical values and the patients scored
      out of a total of 10 points. A score of >7 predicted mandatory operation, 5-6
      observation and score 1-4 predicted those not considered for surgery. The
      decision to operate was the prerogative of the surgeon or surgical resident based
      on overall clinical suspicion and not the diagnostic score. RESULTS: The
      proportion of patients with scores >7 was 40.7%. The mean score was 6.02. The
      mean ages and the gender ratios were similar across score groups. The negative
      appendicectomy rate was 17.6% for group 1-4, 16.5% for 5-6 and 19.7% for >7.
      These were similar to the overall negative rate of 18% based on clinical
      suspicion. The overall sensitivity and sensitivity for the scoring system was
      80.3% and 16.8% respectively. CONCLUSION: High scores were found to perform
      poorly in predicting diagnosis of acute appendicitis preoperatively and in the
      reduction of negative appendicectomies. The integration of a scoring system does
      not offer advantage over degree of clinical suspicion.

PMID- 14601783
TI  - Normal axial angles of the knee joint in adult indigenous Malawians.
AB  - OBJECTIVE: To determine the normal axial angles of the knee joint in adult
      indigenous Malawians. DESIGN: A retrospective study. SETTING: Radiographs were
      collected from the archives of the X-ray Department on subjects investigated from
      Queen Elizabeth Central Hospital in Blantyre City. SUBJECTS: X-ray films of 271
      adult black subjects aged 18-67 years were studied. MAIN OUTCOME MEASURES: Normal
      axial angles of the knee joint using standard methods were determined and
      compared with those reported for Caucasians previously studied. RESULTS: The mean
      femoral and mechanical angles of the femur and the knee joint were greater in
      Malawian subjects than in Caucasians previously reported, but the tibial angle of
      Malawians was less than those of Caucasians. The angle between the mechanical and
      anatomical axes of the femur was 3 degrees in Malawians, but 6 degrees in
      Caucasians. Malawians, had wider range of the mechanical angle of the Knee joint
      than Caucasians. These angles did not show significant sex differences in
      Malawians (P>0.1; 0.5, respectively) but significant differences were observed in
      these angles between Malawians and Caucasians (P>0.001). CONCLUSION: Our study
      has demonstrated comparative variations in means and ranges of normal axial
      angles between Malawians and Caucasians previously reported. Thus as a
      prerequisite for proper orthopaedic clinical practice in this part of the world,
      there is need for reference values of these angles.

PMID- 14601784
TI  - Diagnostic potential of serum vitamin E tocopherol and cholesterol levels in
      children with protein energy malnutrition in western Kenya.
AB  - OBJECTIVE: To determine the levels and diagnostic potential of vitamin E (alpha
      tocopherol) in protein energy malnutrition (PEM) in western Kenya. DESIGN:
      Passive Hospital based study conducted on inpatients and outpatients. SETTING:
      Webuye sub-District and Moi Teaching and referral Hospitals, Western Kenya.
      SUBJECTS AND METHODS: Serum levels for vitamin E and cholesterol concentrations
      in children < 5 years of age (n=56) admitted to Webuye District Hospital,
      Bungoma, Western Kenya and some (n=3) admitted to Moi teaching and referral
      Hospital, Eldoret Kenya suffering from Kwashiorkor, Marasmus or PEM and malaria
      plus there controls, for a period of one year (January-December, 2001) were
      examined. High Performance Liquid Chromatography (HPLC) and Spectrophotometry
      were used for the analysis. RESULTS: The serum vitamin E levels were higher in
      Kwashiorkor (0.078 mg/ml, SD 0.034) than marasmus (0.075 mg/ml; SD 0.069) and
      controls (0.057 mg/ml; SD 0.022). The mean serum cholesterol levels were higher
      in marasmus (204.6 mg/dl; SD 104.8) than Kwashiorkor (186.0 mg/dl; SD 119.3) and
      controls (154.3; SD 33.3). There was a significant correlation in vitamin E
      concentrations between Kwashiorkor and controls only at P<0.01 as compared to
      Marasmus and Marasmic/Kwashiorkor. Vitamin E levels did not show significant
      correlation to cholesterol in malnourished children from Webuye, Bungoma in
      western Kenya at P<0.01. CONCLUSION: Vitamin E could be a useful diagnostic tool
      for PEM in this area.

PMID- 14601785
TI  - Serum albumin, creatinine, uric acid and hypertensive disorders of pregnancy.
AB  - BACKGROUND: Pre-eclampsia is a form of hypertensive disorder of pregnancy. It is
      a common cause of both maternal and perinatal morbidity and mortality in both
      developed and developing countries. OBJECTIVE: To evaluate the possibility of
      early prediction of hypertensive disorders of pregnancy using single estimation
      of serum protein, creatinine and uric in serum samples of healthy primigravidae
      with singleton pregnancy. SETTING: University College Hospital, Ibadan. SUBJECTS:
      Fifty nine normortensive primigravidae. METHODS: Fifty nine healthy normotensive
      primigravidae with singleton pregnancy who booked for antenal care and delivered
      at the University College Hospital, Ibadan had single estimations of their serum
      albumin, creatinine and uric acid levels at booking before the 20th week of
      pregnancy. The women were followed up longitudinally throughout pregnancy.
      RESULTS: Pre-eclampsia occurred in five of the patients (21.7%), two had
      pregnancy induced hypertension only (8.7%) while 16 remained normotensive
      (69.6%). The difference in the mean serum concentration of uric acid (0.162 +/-
      0.02 mmol/L) and creatinine (93.70 +/- 10.08 micromol/L) respectively were not
      statistically significant (p>0.05). However, the difference in the mean serum
      albumin levels (4.06 +/- 0.06 versus 3.71 +/- 0.33 gm/dl) was significantly
      higher in the pre-eclampsia group (p<0.05). The predictive performance of these
      tests was generally low whether alone or in combination. CONCLUSION: Single
      estimation of serum uric acid and creatinine levels early in pregnancy are of
      little value in the prediction of pre-eclampsia. A large study is recommended to
      properly define the value of serum albumin levels in pregnancy in the prediction
      of pre-eclampsia in the light of the findings of this study.

PMID- 14601786
TI  - Salivary gland tumours in Tanzania.
AB  - OBJECTIVE: To determine the pattern of occurrence of salivary gland tumours in
      Tanzania over a period of twenty years. DESIGN: Cross-sectional retrospective
      study. SETTING: Two referral centres; Muhimbili National Hospital (MNH) and
      Kilimanjaro Christian Medical Centre (KCMC). METHODS: Medical records of patients
      who presented with tumours of the salivary glands in the two major referral
      centres over a period of twenty years from 1982 to 2001 were reviewed. Data
      regarding demographic, clinical and histologic information was analysed. RESULTS:
      Salivary gland tumours constituted 6.3% of all oral-facial tumours and tumour
      like lesions. Among the salivary gland tumours, 54% were benign and 46%
      malignant, which occurred in 80 males and 53 females. Peak age was between 20 and
      49 years, with a male-female ratio of 1.5:1 (p<0.05). Pleomorphic adenoma was the
      commonest occurring tumour (44.4%) followed by adenoid cystic carcinoma (24.8%),
      mucoepidermoid carcinoma (9.8%) and adenocarcinoma (6.5%). Among the benign
      tumours, pleomorphic adenoma dominated (83.9%), followed by adenoma (9.9%). Among
      malignant tumours adenoid cystic carcinoma occurred in 54.3% followed by
      mucoepidemoid carcinoma (22.9%) and adenocarcinoma (11.4%). The parotid gland was
      the commonest site of occurrence followed by the palate. At initial stages the
      only complaint from the patients was essentially a slowly growing painless
      swelling. Treatment modality was mainly surgical in both benign and malignant
      tumours, however, for malignant tumours radiotherapy alone or in combination with
      surgery was sometimes employed. CONCLUSION: On average salivary gland tumours
      occurred at a relatively younger age compared to that reported in Western
      countries. Contrary to reports from Europe and America, adenoid cystic carcinoma
      was the most frequently occurring malignant salivary gland tumour. Late
      presentation was seen as a problem that needs to be addressed in order to
      maximise the effectiveness of treatment.

PMID- 14601787
TI  - Pain management in mice using the aqueous and ethanol extracts of four medicinal
      plants.
AB  - BACKGROUND: There are many traditionally used analgesic plants in Ethiopia. They,
      however, have not been subject to scientific investigation for their efficacy and
      safety. OBJECTIVE: To evaluate both prophylactic and relieving effects of aqueous
      and ethanol extracts of four traditionally used medicinal plants in Ethiopia.
      DESIGN: An experimental design in which five group of albino mice weighing 30-35
      grams representing positive and negative control, and extract treated groups
      respectively. The extracts, standard drugs and normal saline were administered
      into GIT by gavage to evaluate the analgesic effect. SETTING: Department of Drug
      Research at Ethiopian Health and Nutrition Research Institute and Department of
      Pharmacology at Faculty of Medicine, Addis Ababa university. METHODS: Analgesic
      effects of water and ethanol extracts of four plants were evaluated against
      distilled water and standard analgesics (morphine and acetylsalicylic acid) with
      acetic acid induced writhing tests in mice. The four plants used for this
      screening were Ocimum sauve, Ocimum lamiifolium, Lippia adoensis and Ajuga
      remota. RESULTS: All extracts of the four plant materials were observed to
      possess both inhibiting and treatment activities against acetic acid induced
      pain. Dose related analgesic effect was also observed with all extracts of all
      plants with different potencies. Ethanol extracts of all the four plant materials
      were more potent than their water extracts at all dose levels except O. sauve,
      and L. adoensis whose water extracts seem to be a bit more potent at low dose.
      The analgesic potencies of both extracts of all the four plants were shown to be
      less than those of the standard analgesics. Of all the extracts, the ethanol
      extract of O. lamiifolium was found to be the most potent, while its water
      extract was the least. Acetic acid induced writhing was relieved with medium dose
      of both extracts in most cases and with low dose in few. Hundred percent relief
      was achieved with both standard analgesics at a very low dose. CONCLUSION: The
      present study show that all the extracts of all the plant materials have got both
      inhibiting and relieving effects of pain.

PMID- 14601789
TI  - Stroke web site and World-Stroke Mailing List: project report II.

PMID- 14601788
TI  - Visceral leishmaniasis with concomittant post kala-azar dermal leishmaniasis
      responds to oral sitamaquine: case report.
AB  - We report a rare case of visceral leishmanisis with concomitant post kala-azar
      dermal leishmaniasis as the initial presentation in a female patient from Baringo
      district, Rift valley province, Kenya.

PMID- 14601790
TI  - Critical point of body fat percentage in obese Japanese.

PMID- 14601791
TI  - Building up a picture of VN training and employment.

PMID- 14601792
TI  - Veterinary opportunities in beef production.

PMID- 14601793
TI  - Dealing with the threat of bioterrorism and exotic disease.

PMID- 14601794
TI  - Role of practitioners in state veterinary service programmes.

PMID- 14601795
TI  - Diagnosis and treatment of retropharyngeal injuries in lambs associated with the
      administration of intraruminal boluses.
AB  - The administration of intraruminal identification boluses to a group of 76 lambs
      resulted in 24 (32 per cent) showing signs of pharyngeal damage. In 16 of them
      the bolus was found to be in the retropharyngeal region by means of a hand-held
      microchip scanner, radiography and endoscopy. Purulent tracts were identified in
      the dorsal pharynx. In 13 of the 16 lambs the surgical removal of the bolus under
      general anaesthesia was followed by a normal clinical recovery, although the
      lambs did not grow as well as similar unaffected animals; three of the 24 lambs
      died. The administration of a larger bolus to 10 yearling rams did not result in
      any clinical signs of pharyngeal damage. The most important factors influencing
      the occurrence of this type of injury among this group of lambs were the size and
      age of the lambs, the positioning of the lambs during bolus administration, the
      relative size of the dosing gun and bolus, and the large number of animals in the
      group.

PMID- 14601796
TI  - Study of the clinical effects of postoperative parenteral nutrition in 15 horses.
AB  - Several clinical variables were compared in two groups of 15 horses recovering
      from resection and anastomosis of a strangulated small intestine; 15 were treated
      with parenteral nutrition and 15 were starved routinely. There was some evidence
      that parenteral nutrition had a short-lived adverse effect on both the catheter
      sites and gastric emptying, but there were no marked adverse clinical effects and
      no evidence of any improvement in the horses' condition.

PMID- 14601797
TI  - Detection of canine distemper virus antigen in canine serum and its application
      to diagnosis.
AB  - Canine distemper virus (CDV) antigen was detected in the serum of dogs by an
      ELISA and the results of this assay were compared with an anti-CDV immunoglobulin
      M (IgM) antibody test. In paired sera from 26 naturally infected dogs, the
      antigen-positive rate was 26.9 per cent at the first examination and 11.5 per
      cent at the second examination two to three weeks later. The antigen was detected
      in three of the 10 dogs which were negative for anti-CDV IgM antibody at the
      first examination. It could also be detected in the serum of between eight and
      two of 40 specific pathogen-free dogs vaccinated against CDV, for up to four
      weeks after they were vaccinated.

PMID- 14601798
TI  - Immune-mediated thrombocytopenia and putative haemolytic anaemia associated with
      a polyvalent botulism vaccination in a cow.

PMID- 14601799
TI  - Identification of foot-and-mouth disease from a captive kangaroo in a zoological
      garden in India.

PMID- 14601800
TI  - FMD control strategies.

PMID- 14601801
TI  - Farm assurance schemes.

PMID- 14601802
TI  - Koi herpesvirus in wild fish.

PMID- 14601803
TI  - Need for clinical audit.

PMID- 14601804
TI  - What is a profession?

PMID- 14601805
TI  - Scrapie genetic susceptibility in Portuguese sheep breeds.

PMID- 14601806
TI  - Occupation: on the rocks.

PMID- 14601807
TI  - Your personal commitment.

PMID- 14601808
TI  - Northern Initiative for Social Action: an occupation-based mental health program.
AB  - Northern Initiative for Social Action (NISA) is a consumer-run, occupation-based,
      nonprofit organization located in northeastern Ontario, Canada. The NISA
      organization has grown in response to research revealing few opportunities for
      participation in personally meaningful and socially valued occupation for persons
      with mental illness living in the community of study. This article describes a
      mixed-design research study conducted by the ParNorth Research Unit of NISA and
      an occupational therapist. The study purposes were to (a) better understand the
      emerging characteristics of the NISA program and identify which the participants
      found helpful; (b) evaluate whether participation in NISA improved members'
      quality of life; and (c) ascertain whether participation reduced members' need
      for more traditional and costly methods of care (e.g., hospitalization, crisis
      services). Focus groups, daily participant observation, a quality of life
      interview, a consumer member survey and objective review of hospitalization data
      were used for data collection. Qualitative results indicated that NISA helped to
      meet participants' being, belonging, and becoming needs. Quantitative data
      indicated that overall, NISA members perceive an improvement in their subjective
      quality of life and sense of well-being. Their perceptions are supported by
      minimal use of crisis services and hospitalization, improved socioeconomic
      status, and several members' success in obtaining paid employment either within
      or outside NISA. Future challenges include the need to clearly describe the
      evolving NISA model and to ensure that the growth of this new organization does
      not exceed secured human or fiscal resources.

PMID- 14601809
TI  - The New Stories/New Cultures after-school enrichment program: a direct cultural
      intervention.
AB  - This article describes the organization, curriculum, and outcomes for New
      Stories/New Cultures, an activity-based program for after-school enrichment in
      five schools in the low-income neighborhood near a major American university. The
      program encourages students (70% Hispanic-American, 30% African-American) to
      experience themselves as producers of culture, not just as consumers. Its methods
      include (a) creative team use of video equipment and other expressive media and
      (b) lessons about media literacy (i.e., making critical choices about images and
      activities depicted in popular culture and commercials). Outcome measures with
      the cohort of fifth and sixth graders support the programs occupation-based
      philosophy. They show that students are more likely to experience themselves as
      building skills when engaged in activities that are both challenging and
      enjoyable. The students reported greatest engagement and enjoyment in activities
      that were creative, team-based, and involving media production. These same
      activities were correlated with increased self-esteem. The term direct cultural
      intervention is used to describe the application of occupational principles and
      critical perspectives to provide a population with conceptual tools and skills
      for interpreting and successfully navigating the social world.

PMID- 14601810
TI  - The use of service dogs as an adaptive strategy: a qualitative study.
AB  - OBJECTIVE: The purpose of this study was to describe, qualitatively the use of
      service dogs by persons with physical disabilities and the meaning of this
      experience. METHOD: Five service dog owners were observed and interviewed on
      multiple occasions through an ethnographic approach. RESULTS: Identified themes
      were increased community participation, "closer than family" increased social
      contact, personal skill development, having fun, responsibility, adjustment,
      challenges, independence, "someone to watch over me," and "feel like an able
      bodied person." CONCLUSION: Service dogs are used to enhance independence in
      occupational performance areas and contribute to improvements in psychosocial
      functioning. Given these benefits, service dogs could be viewed as a form of
      assistive technology that occupational therapists may want to consider as an
      alternative to traditional devices for some clients.

PMID- 14601811
TI  - The relationship between the Evaluation Tool of Children's Handwriting and
      teachers' perceptions of handwriting legibility.
AB  - OBJECTIVE: The purpose of this study was to investigate the relationship between
      the Evaluation Tool of Children's Handwriting (ETCH) and teachers perception of
      handwriting legibility METHODS: The ETCH was administered to 45 first-grade
      students with illegible handwriting as reported by their teachers. The teachers
      completed a teachers questionnaire at the same time to indicate the children's
      level of handwriting difficulties both in general and in specific tasks that
      resemble the test tasks of the ETCH. RESULTS: There was no significant
      relationship between the ETCH scores and the teacher questionnaire scores in
      either general legibility or task-specific legibility. CONCLUSION: The ecological
      validity of the ETCH, in reference to the teachers' perception of handwriting
      legibility, was not established. Further changes for scoring criteria may be
      warranted before the ETCH can be used with confidence that the scores obtained
      are meaningfully related to actual performance in the classroom as determined by
      teachers.

PMID- 14601812
TI  - Construct-related validity of the Toglia Category Assessment and the Deductive
      Reasoning test with children who are typically developing.
AB  - OBJECTIVE: Both classification and deductive reasoning are essential cognitive
      components underlying any learning process and, therefore, are important to
      assess in children with developmental or learning disabilities. The aim of this
      study was to establish construct-related validity of the Toglia Category
      Assessment (TCA) and the Deductive Reasoning test, which were originally
      developed to evaluate adults with brain injury. This study represents the first
      step in validating and adapting the two tests for children who are typically
      developing. METHOD: The study population consisted of 235 children without
      disabilities in 6 different age groups (from 5-11 years of age). Both the TCA and
      the Deductive Reasoning test were administered to all participants. RESULTS: The
      results of the study indicate significant differences in the average performance
      of children in several age groups on both the TCA and the Deductive Reasoning
      test, but they do not show differences among all the groups. Children could not
      predict their ability in either test, but most were able to estimate their
      ability after actual performance of the TCA. A significant correlation was found
      only for the 5-year-olds and 7-year-olds between the Deductive Reasoning test
      final score and the children's estimation of their performance. CONCLUSION: The
      findings of this study support the suitability of the TCA and the Deductive
      Reasoning test for use with children who are typically developing. We recommend
      that both tools be studied further to amplify their validity.

PMID- 14601813
TI  - Occupational Adaptation model versus biomechanical-rehabilitation model in the
      treatment of patients with hip fractures.
AB  - OBJECTIVE: This study compared the effectiveness of the Occupational Adaptation
      frame of reference with the biomechanical-rehabilitation model in the treatment
      of two groups of 20 patients post-hip fracture. METHOD: Using a quasi
      experimental design, groups were compared on changes in scores on the Functional
      Independence Measure (FIM), a satisfaction questionnaire developed for this study
      and discharge environment. RESULTS: No group differences in FIM changes for the
      total stay were found. However, average FIM score change per day of
      hospitalization and overall patient satisfaction were higher in the
      OccupationalAdaptation group. No significant differences in the discharge
      environment were present. CONCLUSION: Both groups benefited from occupational
      therapy intervention. Occupational Adaptation was associated with a more
      efficient outcome and greater patient satisfaction.

PMID- 14601814
TI  - Participation in daily living tasks among older adults with fear of falling.
AB  - OBJECTIVE: This study investigated patterns of participation in daily living
      tasks by older adults with fear of falling. The relationship between reported
      participation in a broad set of daily living tasks and the risk of falling
      involved in task performance--or activity-related risk--as judged by occupational
      therapists was examined. Further, several characteristics of older adults that
      have been associated with fear of falling were examined to determine which older
      adults had patterns of participation most strongly associated with the activity
      related risk. METHOD: Thirty-eight occupational therapists were surveyed and
      asked to judge the activity-related risk in performing specific daily living
      tasks. Additional data were obtained from 339 older adults with fear of falling
      who participated in a previous study on the effectiveness of an intervention to
      reduce fear of falling. Older adults' participation in daily living tasks as
      measured by items of the Sickness Impact Profile was correlated with the
      judgments of activity-related risk controlling for potential confounding factors.
      Univariate regression analyses and t tests were used to determine whether several
      characteristics of older adults were associated with the relationship between
      participation and activity-related risk. RESULTS: Small to moderate significant
      relationships were found between older adults' participation in daily living
      tasks and the activity-related risk as judged by occupational therapists (r = 
      .25, p < .0001). Older adults with the lowest confidence in ability regarding
      falls had the strongest relationships. CONCLUSION: Activity-related risk is an
      aspect of daily living tasks that relates to participation in activities by older
      adults with fear of falling. Knowledge of the activity-related risk involved in
      daily living tasks can be used to facilitate occupational performance in clients
      with fear of falling and associated activity restriction.

PMID- 14601815
TI  - Describing and predicting the possession of assistive devices among persons with
      multiple sclerosis.
AB  - OBJECTIVE: This study describes the types of assistive devices in the possession
      of persons with multiple sclerosis (MS) and identifies factors that best
      predicted the probability of possessing these devices. METHOD: A secondary
      analysis using frequency distributions and logistic regression of existing cross
      sectional data was completed. Data were from an anonymous mail survey of members
      of the Multiple Sclerosis Society of Canada (Atlantic Division) (N = 906).
      RESULTS: Mobility aids and grab bars were the most commonly reported assistive
      devices. Seeing an occupational therapist, not working, having a progressive type
      of MS, having more activity limitations and more symptoms, and having MS for a
      longer period were found to increase the probability of possessing assistive
      devices. CONCLUSION: The descriptive results of this study are similar to studies
      of assistive technology use by older adults and persons with other chronic
      conditions. Type of MS and seeing an occupational therapist were the two
      strongest predictors of possessing assistive devices among respondents.

PMID- 14601816
TI  - Use of the UFOV to evaluate and retrain visual attention skills in clients with
      stroke: a pilot study.
AB  - OBJECTIVE: The objective of this pilot study was to examine the use of a visual
      attention analyzer in the evaluation and retraining of useful field of view in
      clients with stroke. METHOD: Fifty-two clients with stroke referred to a driving
      evaluation service were evaluated with a visual attention analyzer referred to as
      the UFOV. The UFOV assesses three aspects of visual attention: processing speed,
      divided attention, and selective attention. Seven participants were retested to
      determine the test-retest reliability of the UFOV. Six participated in the
      development of a training protocol and in a 20-session visual attention
      retraining program. RESULTS: UFOV scores indicated substantial reduction in
      visual attention in clients after stroke, with older participants performing the
      most poorly. Test-retest reliability was moderate (ICC = .70). Mean UFOV scores
      improved significantly after retraining. CONCLUSION: Although UFOV scores
      indicated poor visual attention skills in clients with stroke, preliminary
      information suggests that UFOV scores significantly improve with training.

PMID- 14601817
TI  - The effect of contextual relevance on motor skill transfer.
AB  - OBJECTIVE: The purpose of this study was to investigate whether practicing a
      complex self-care occupation in a contextually relevant environment would enhance
      the learning and transfer of skill. METHOD: The design consisted of an
      acquisition phase, a rest period, and a transfer phase. Fifty-six women were
      recruited for this study and randomly assigned to one of three groups: (a) a
      contextually relevant (CR) group that practiced tying a necktie knot onto a
      mannequin, (b) a non-contextually relevant (NCR) group that practiced tying the
      same type of knot with a rope onto a wooden pole, and (c) a control group that
      did not practice at all during the acquisition phase. Participants in all three
      groups tied a necktie onto themselves during the transfer phase. Dependent
      variables were movement time, movement units, and the quality of the necktie
      knot. RESULTS: No difference in the rate of performance change was found during
      the acquisition phase between the CR and NCR groups. The difference among the CR,
      NCR, and control groups' initial transfer phase performance was near significance
      for movement time and movement units. A significant difference in the rate of
      performance change was found among the three groups in movement time and movement
      units during the transfer phase but not in the quality of necktie knot measures.
      CONCLUSION: The degree of similarity during the acquisition of a dressing skill
      may influence the rate of performance improvement in a similar dressing skill
      during a transfer phase. Until further research has been established,
      generalization of these results to special populations should be done
      conservatively.

PMID- 14601818
TI  - Rethinking the use of the Hogan Empathy Scale: a critical psychometric analysis.
AB  - OBJECTIVE: The purpose of this research was to study the stability internal
      consistency factor structure, and convergent and discriminate validity of the
      Hogan Empathy Scale (EM) when used longitudinally with occupational therapy
      students. METHOD: More than 300 occupational therapy students completed the EM
      once; 192 completed it twice over a 12-month interval; and 56 completed a third
      administration at intervals ranging from 3 years to 6 years. The Fieldwork
      Performance Evaluation (FWPE) was rated twice for students after fieldwork
      rotations in the occupational therapy program. Data on grade-point average,
      gender, and age were collected. RESULTS: Stability was estimated at .41 over a 12
      month interval and from .30 to .38 over longer intervals. Internal consistency
      was estimated at .57, and factor structures hypothesized previously were not
      replicable. Students' biographical variables explained only trivial amounts of
      variance in EM scores in regression equations (R = .08 and .21). Correlations
      between EM and FWPE scores did not support convergent validity (r = -. 01-.18).
      CONCLUSION: The reliability estimates for the EM as a measure of a trait-like
      construct are not encouraging and do not replicate previous estimates. Validity
      evidence was equally disappointing, raising questions about what the EM is
      measuring and cautioning against its continued, uncritical use as a measure of
      empathy.

PMID- 14601819
TI  - Physical properties of short-stretch compression bandages used to treat
      lymphedema.
AB  - This study examined the physical properties of six common brands of short-stretch
      compression bandages used to treat lymphedema. The physical properties examined
      were (a) maintenance of pressure over a 12-hr period, (b) variability of pressure
      across the width of the bandages, and (c) variability of pressure when the
      bandages were wrapped with a 50% overlap. The results of the study indicate that
      all six brands of bandages tested maintain pressure well over a 12-hr period.
      Each has a variance of pressure between the middle and edge of the bandage, with
      the edges measuring (in mmHg) between 6% and 28% lower than the middle. When the
      bandages were wrapped with an 50% overlap, all six brands measured fairly
      consistently in pressure readings (in mmHg) across the width. These results
      indicate that the six brands of short-stretch compression bandages tested have
      similar physical characteristics.

PMID- 14601820
TI  - The clinical reasoning of an occupational therapy assistant.
AB  - This qualitative case study focused on the clinical reasoning of a certified
      occupational therapy assistant who had 16 years of practice experience.
      Observation and interview methods were used to collect data. Transcripts and
      field notes were coded using a priori codes of the forms of clinical reasoning of
      occupational therapists identified in published research. The study participant
      demonstrated the use of pragmatic, procedural, interactive, conditional, and
      narrative reasoning. We encourage further research to support these findings and
      to increase the understanding of the forms of clinical reasoning used by
      occupational therapy assistants.

PMID- 14601821
TI  - Using a head-mounted video camera to study clinical reasoning.
AB  - Studies of clinical reasoning are essential if we are to extend our knowledge of
      occupational therapy practice, better communicate our work to clients and
      colleagues, and reveal to our students the nuances of therapy that cannot be
      gained from texts. However, accessing therapists' clinical reasoning is not an
      easy task because these cognitive processes can be studied only indirectly. The
      aim of this article is to promote the study of clinical reasoning by reviewing a
      new approach to data collection in this field. To achieve this purpose, the
      article outlines current data collection methods, such as the think-aloud method
      written notes, free recall, and audio-assisted and video-assisted recall. A novel
      method involving a head-mounted video camera is described, and details are
      provided on a modified approach to debriefing using video-assisted recall.
      Anecdotes from the authors experience of using this technology illustrate the
      text.

PMID- 14601822
TI  - Teaching evidence-based practice using the American Academy of Cerebral Palsy and
      Developmental Medicine methodology.

PMID- 14601823
TI  - Determination of volatile aliphatic amines in air by solid-phase microextraction
      coupled with gas chromatography with flame ionization detection.
AB  - Practical aspects of the application of solid-phase microextraction (SPME) to the
      determination of volatile aliphatic amines in air are described. Analytes
      included methylamine (MA), ethylamine (EA), dimethylamine (DMA), diethylamine
      (DEA), trimethylamine (TMA) and triethylamine (TEA). New SPME stationary phases
      were examined. The effects of relative humidity and temperature on analytes
      uptake were taken into account in analysis. Gas chromatography (GC) with flame
      ionization detector (FID) was used for the final analysis.

PMID- 14601824
TI  - Determination of organic micropollutants in rainwater using hollow fiber
      membrane/liquid-phase microextraction combined with gas chromatography-mass
      spectrometry.
AB  - A simple and rapid liquid-phase microextraction (LPME) method using a hollow
      fiber membrane (HFM) in conjunction with gas chromatography-mass spectrometry (GC
      MS) is presented for the quantitative determination of 16 polycyclic aromatic
      hydrocarbons (PAHs) and 12 organochlorine pesticides (OCPs) in rainwater samples.
      The LPME conditions were optimized for achieving high enrichment of the analytes
      from aqueous samples, in terms of hollow fiber exposure time, stirring rate,
      sample pH, and composition. Enrichment factors of more than 100 could be achieved
      within 35 min of extraction with relative standard deviations (R.S.D.s) 1.3-13.6%
      for PAHs and 1.7-13.8% for OCPs, respectively, over a wide range of analyte
      concentrations. Detection limits ranged from 0.002 to 0.047 microg l(-1) for
      PAHs, and from 0.013 to 0.059 microg l(-1) for OCPs, respectively. The newly
      developed LPME-GC-MS method has been validated for the analysis of PAHs and OCPs
      in rainwater samples. Extraction recoveries from spiked synthetic rainwater
      samples varied from 73 to 115% for PAHs and from 75 to 113% for OCPs,
      respectively. Real rainwater samples were analyzed using the optimized method.
      The concentrations of PAHs and OCPs in real rainwater samples were between 0.005
      0.162, and 0.063 microg l(-1), respectively.

PMID- 14601825
TI  - Preparation and characterization of prototypes for multi-modal separation media
      aimed for capture of negatively charged biomolecules at high salt conditions.
AB  - Several prototypes of multi-modal ligands suitable for the capture of negatively
      charged proteins from high conductivity (28 mS/cm) mobile phases were coupled to
      Sepharose 6 Fast Flow. These new prototypes of multi-modal anion-exchangers were
      found by screening a diverse library of multi-modal ligands and selecting anion
      exchangers resulting in elution of test proteins at high ionic strength.
      Candidates were then tested with respect to breakthrough capacity of BSA in a
      buffer adjusted to a high conductivity (20 mM Piperazine and 0.25 M NaCl, pH
      6.0). The recovery of BSA was also tested with a salt step (from 0.25 to 2.0 M
      NaCl using 20 mM Piperazine as buffer, pH 6.0) or with a pH-step to pH 4.0. We
      have found that non-aromatic multi-modal anion-exchange ligands based on primary
      or secondary amines (or both) are optimal for the capture of proteins at high
      salt conditions. Furthermore, these new multi-modal anion-exchange ligands have
      been designed to take advantage not only of electrostatic but also hydrogen bond
      interactions. This has been accomplished through modification of the ligands by
      the introduction of hydroxyl groups in the proximity of the ionic group.
      Experimental evidence on the importance of the relative position of the hydroxyl
      groups on the ligand in order to improve the breakthrough capacity of BSA has
      been found. Compared to strong anion-exchangers such as Q Sepharose Fast Flow the
      new multi-modal weak anion-exchangers have breakthrough capacities of BSA at
      mobile phases of 28 mS/cm and pH 6.0 that are 20-30 times higher. The new multi
      modal anion-exchangers can also be used at normal anion-exchange conditions and
      with either a salt step or a pH-step to acidic pH can accomplish the elution of
      proteins. In addition, the functional performance of the new anion-exchangers was
      found to be intact after treatment in 1.0 M sodium hydroxide solution for 1 week.
      A number of multi-modal anion-exchange ligands based on aromatic amines
      exhibiting high breakthrough capacity of BSA have been found. With these ligands
      recovery was often found to be low due to strong non-electrostatic interactions.
      However, for phenol derived anion-exchange media the recovery can be improved by
      desorption at high pH.

PMID- 14601826
TI  - Preparation and characterization of prototypes for multi-modal separation aimed
      for capture of positively charged biomolecules at high-salt conditions.
AB  - Several prototypes of aromatic (Ar) and non-aromatic (NoAr) cation-exchange
      ligands suitable for capture of proteins from high conductivity (ca. 30 mS/cm)
      mobile phases were coupled to Sepharose 6 Fast Flow. These new prototypes of
      multi-modal cation-exchangers were found by screening a diverse library of multi
      modal ligands and selecting cation-exchangers resulting in elution of test
      proteins at high ionic-strength. Candidates were then tested with respect to
      breakthrough capacity of bovine serum albumin (BSA), human IgG and lysozyme in
      buffers adjusted to a high conductivity. By applying a salt-step or a pH-step the
      recoveries were also tested. We have found that aromatic multi-modal cation
      exchanger ligands based on carboxylic acids seem to be optimal for the capture of
      proteins at high-salt conditions. Experimental evidence on the importance of the
      relative position of the aromatic group in order to improve the breakthrough
      capacity at high-salt conditions has been found. It was also found that an amide
      group on the alpha-carbon was essential for capture of proteins at high-salt
      conditions. Compared to a strong cation-exchanger such as SP Sepharose Fast Flow
      the best new multi-modal weak cation-exchangers have breakthrough capacities of
      BSA, human IgG and lysozyme that are 10-30 times higher at high-salt conditions.
      The new multi-modal cation-exchangers can also be used at normal cation-exchange
      conditions and with either a salt-step or a pH-step (to pH-values where the
      proteins are negatively charged) to accomplish elution of proteins. In addition,
      the functional performance of the new cation-exchangers was found to be intact
      after treatment in 1.0 M sodium hydroxide solution for 10 days. For BSA it was
      also possible to design cation-exchangers based on non-aromatic carboxyl acid
      ligands with high capacities at high-salt conditions. A common feature of these
      ligands is that they contain hydrogen acceptor groups close to the carboxylic
      group. Furthermore, it was also possible to obtain high breakthrough capacities
      for lysozyme and BSA of a strong cation-exchanger (SP Sepharose Fast Flow) if
      phenyl groups were attached to the beads. Varying the ligand ratio (SP/Phenyl)
      could be used for optimizing the function of mixed-ligand ion-exchange media.

PMID- 14601827
TI  - Use of cholate derivatives with submicellar concentration for controlling
      selectivity of proteins in hydrophobic interaction chromatography.
AB  - Hydrophobic interaction chromatography (HIC) of proteins using a phenyl column
      has been performed in the presence of various surfactants with micellar and
      submicellar concentration ranges. Most surfactants were effective for a decrease
      in the retention of proteins in both concentration ranges. However, the use of
      anionic cholate derivatives increased the retention of the proteins with high
      isoelectric point, such as lysozyme, cytochrome c, and trypsin, in submicellar
      concentration range, and then decreased it above the critical micellar
      concentration, while the retention of the other proteins was monotonously
      decreased. The results of frontal chromatographic analysis of the surfactant and
      capillary electrophoresis for the proteins in the presence of surfactant show
      that in the submicellar concentration range, cholate derivatives allowed to be
      adsorbed on the stationary phase, while they exhibited no interactions with the
      proteins. Thus, it appeared that the increase in the retention of basic proteins
      was due to the electrostatic attraction between the proteins and cholate-modified
      stationary phase. We have applied the unique property of cholate to the
      separation of ovalbumin and lysozyme in egg white sample using hydrophobic
      chromatography.

PMID- 14601828
TI  - Characterization of polychlorinated aromatic hydrocarbons by reversed-phase
      liquid chromatography with ultraviolet absorbance and mass spectrometric
      detection.
AB  - Ten polychlorinated aromatic hydrocarbons (PCAHs), perchlorobenzene (I),
      perchlorobiphenyl (II), perchlorobenzo[f]inden-1-one (III), perchloronaphthalene
      (IV), perchloropenta[def]phenanthren-4-one (V), 6H-1,2,4,5,7,8,9,10,11
      nonachlorobenzo[cd]pyrene-3-one (VI), perchloroacenaphthylene (VII), 6-(p-tolyl)
      6H-1,2,3,4,5,7,8,9,10,11-decachlorobenzo[cd]pyrene (VIII), perchlorofluoranthene
      (IX) and 6-(p-tolyl)-6H-1,11-dihydroxy-2,3,4,5,7,8,9,10-octachlorobenzo[cd]pyrene
      (X) have been separated with reversed-phase liquid chromatography (RPLC) by using
      two gradient eluents (toluene/methanol and cyclohexane/methanol), and were
      detected by ultraviolet (UV) and mass spectrometry (MS). The separation and
      detection of half of these ten compounds, which are of extremely high molecular
      weights, is an improvement over the chromatographic analysis of PCAHs. When the
      procedure was applied to the analysis of PCAHs of the products from the
      combustion of chlorobenzene and carbon tetrachloride, I, II, IV, VIII and X could
      be detected.

PMID- 14601829
TI  - Profiling of N-linked oligosaccharides using phenylhydrazine derivatization and
      mass spectrometry.
AB  - N-linked oligosaccharide standards obtained from commercial sources were
      derivatized with phenylhydrazine (PHN) and analyzed by on-line reversed-phase
      high performance liquid chromatography (HPLC)/electrospray ionization mass
      spectrometry (ESI-MS). This procedure was then applied to mixtures of N-glycans
      enzymatically released from hen ovalbumin. Under ESI-MS conditions,
      phenylhydrazones of asialylated oligosaccharide standards and ovalbumin glycans
      produced mainly [M + 2H]2+ molecular ions at low cone voltage values, while
      minimal fragmentation was observed. Reversed-phase HPLC/ESI-MS total and selected
      ion chromatograms obtained for derivatized N-glycans from ovalbumin showed
      partial but useful separation. Overall glycan profiles obtained by ESI-MS were
      compared with results obtained by matrix-assisted laser desorption/ionization
      (MALDI)-MS. Qualitatively, profiles were similar from one technique to the other
      in terms of relative abundance of glycans versus composition. Post-source decay
      (PSD) analysis of the [M + Na]+ ions of PHN-glycans showed dominant B, C and
      internal B/Y, C/Y cleavages. These patterns were helpful in relating
      fragmentation to proposed structures. Cross-ring cleavage fragment ions (A-type)
      were also observed in most cases. The PHN derivatization method is fast and
      simple. It produces abundant parent ions in both MALDI-MS and ESI-MS, while
      avoiding the presence of salt contaminants during the labeling procedure.

PMID- 14601830
TI  - Investigation of phenolic acids in yacon (Smallanthus sonchifolius) leaves and
      tubers.
AB  - Thin-layer chromatographic (TLC) screening of crude extracts of dried leaves and
      tubers of yacon (Smallanthus sonchifolius, Asteraceae) and products of acid
      hydrolysis of tubers on the silica gel HPTLC plates using the developing solvents
      ethyl acetate-formic acid-water (85:10:15, v/v/v) and n-hexane-ethyl acetate
      formic acid (20:19:1, v/v/v) proved the presence of chlorogenic, caffeic and
      ferulic acid. These phenolic acids were isolated from the crude extract of yacon
      leaves by preparative TLC, and identified after elution by HPLC/MS, as well as by
      direct injection of the crude extract into the HPLC/MS system. Acid hydrolysis of
      tubers released the increased amount of phenolic acids (e.g. caffeic acid and
      ferulic acid), flavonoid quercetin and an unidentified flavonoid, which was
      detected by TLC analysis. Ferulic acid, isomers of dicaffeoylquinic acid and
      still an unidentified derivative of chlorogenic acid (Mr = 562) as constituents
      of yacon leaves and ferulic acid as constituent of yacon tubers are reported here
      for the first time. These acids gave significant contribution to the radical
      scavenging activity detected directly on the TLC plate sprayed with 1,1-diphenyl
      2-picrylhydrazyl (DPPH).

PMID- 14601831
TI  - Determination of the volatile chemical constituents of Notoptergium incium by gas
      chromatography-mass spectrometry and iterative or non-iterative chemometrics
      resolution methods.
AB  - The qualitative and quantitative determination of the chemical constitutes in
      traditional Chinese medicine (TCM) is an important task, which builds the
      foundation of the theory of pharmacological activity. The hyphenated
      chromatography instruments combined with the related chemometric methods provide
      powerful tools for the resolution of such complex systems. The familiar
      chemometrics methods can be roughly divided into two different kinds, the
      iterative one such as orthogonal projection approach (OPA) and non-iterative one
      representing by evolving window orthogonal projection (EWOP). One can use
      different kinds of methods according to overlapping condition, and then the
      measured data matrix can be resolved into pure concentration profiles and mass
      spectra of the chemical components with relative high efficiency and acceptable
      accuracy. One kind of TCM, named Notoptergium incium (NI) was analyzed by gas
      chromatography-mass spectrometry (GC-MS) and resolved by above chemometric
      approach. Experiment results show the efficiency and convenience of the proposed
      approach. 65 of the 98 separated constituents in essential oil, accounting for
      92.13%, were identified by mass spectroscopy (MS).

PMID- 14601832
TI  - Isolation of ceramide fractions from skin sample by subcritical chromatography
      with packed silica and evaporative light scattering detection.
AB  - Separative method of lipid classes from the stratum corneum was developed with
      packed silica and supercritical CO2 containing 10% of methanol at 15 degrees C,
      15 MPa and 3 ml min(-1). The elution order of lipid classes was first esterified
      cholesterol, triglycerides, squalene co-eluted in a single peak, then free fatty
      acids, free cholesterol, ceramides and finally glycosylceramides. The ceramides
      were eluted in several fractions which depended on the number of hydroxyl groups
      in the molecule, i.e. more hydroxyl groups were contained in ceramides, more
      important was the retention. Moreover, the retention was not altered by the
      presence of carbon double bond and variation of the alkyl chain length. The
      ceramide response with the evaporative light scattering detector was improved by
      turning the influence of the solvent nature on the response to advantage.
      Therefore, addition of various solvents with or without triethylamine and formic
      acid were tested in post-column due to the incompatibility of such modifiers with
      silica stationary phase. Thereby the solvent conditions for the separation and
      the detection can be adjusted almost independently. The response was greatly
      increased by post-column addition of 1% (v/v) triethylamine and its equivalent
      amount of formic acid in dichloromethane introduced at 0.1 ml min(-1) into the
      mobile phase. This device had allowed the detection of 400 ng of ceramide with a
      S/N = 21, whereas no peak was observed in absence of the post-column addition.
      Finally, the method was applied to the treatment of skin sample which led to
      highly enriched ceramide fraction.

PMID- 14601833
TI  - Determination of hydroxyl radical by capillary zone electrophoresis with
      amperometric detection.
AB  - Hydroxyl radical (OH*) can cause severe damage to cells and tissues. However, its
      analysis is very difficult for its high reactivity and very short half-life. In
      this paper, a simple and highly sensitive method, capillary zone electrophoresis
      with amperometric detection (CZE-AD) was introduced indirectly to determine OH*
      by determining its reaction products with salicylic acid (SAL), 2,3
      dihydroxybenzoic acid (2,3-DHBA) and 2,5-dihydroxybenzoic acid (2,5-DHBA). The
      optimum conditions of CZE-AD for the determination of 2,3-DHBA and 2,5-DHBA were
      explored. Under the optimum conditions, SAL, 2,3-DHBA and 2,5-DHBA could be
      perfectly separated within 15 min, and the linearity ranges of 2,3-DHBA and 2,5
      DHBA were between 1.0 x 10(-7) and 1.0 x 10(-4) mol l(-1). Their detection limits
      were as low as 2 x 10(-8) mol l(-1), which were much lower than that in CE-UV
      method. The method was also applied to study the free OH* scavenging activity of
      angelica polysaccharide. The experimental results showed that this CZE-AD method
      was very sensitive and practical in both the determination of free OH* and the
      evaluation of free OH* scavenging activities of antioxidants.

PMID- 14601834
TI  - Extracolumn band broadening in capillary liquid chromatography.
AB  - A commercially available capillary LC instrument was modified to investigate and
      control the contribution of different instrument components on extracolumn band
      broadening. Quantitative estimations of dispersion induced by several equipmental
      parts were carried out. Injection parameters could be optimized to achieve the
      theoretical value of 12 for a profile factor describing a rectangular sample
      profile. Additionally, an additive injector flow channel dependent dispersion
      effect was found. A practical approach for minimizing instrumental effects in
      capillary LC is suggested. The results were compared with those obtained with an
      HPLC instrument designed for conventional size columns.

PMID- 14601835
TI  - Adsorption isotherms and retention behavior of 1,1'-bis(2-naphthol) on CHIRIS AD1
      and CHIRIS AD2 columns.
AB  - The separation of the atropoisomers of 1,1'-bis(2-naphthol) was studied on CHIRIS
      AD1 and CHIRIS AD2, two Pirkle-type chiral stationary phases. Satisfactory
      selectivity was found only on CHIRIS AD2. The ternary mobile phases comprised
      hexane, dichloromethane and methanol. The effects of their composition and of the
      temperature on the retention under analytical conditions and on the single
      component and competitive isotherms were investigated. The retention of the R-
      and S-isomers on CHIRIS AD1 and CHIRIS AD2 is controlled by the enthalpic
      contribution to adsorption, but the effect of the mobile phase on the retention
      should be attributed mainly to the entropic contribution. The adsorption of the
      less retained R-isomer is controlled by the achiral interactions, which are the
      same as for the S-isomer. The single-component and competitive isotherms of the R
      and S-isomers are adequately described by the sum of a Langmuir term for the
      achiral contribution to adsorption and a linear-term characterising the selective
      or chiral adsorption of the S-isomer in the concentration range experimentally
      available, i.e. within the solubility limit of 1,1'-bis(2-naphthol).

PMID- 14601836
TI  - Use of mobile phase 18-crown-6 to improve peak resolution between mono- and
      divalent metal and amine cations in ion chromatography.
AB  - It is difficult to quantify NH4+ by ion chromatography in the presence of high
      concentrations of Na+ due to peak overlap. The Dionex IonPac CS15 column, which
      contains phosphonate, carboxylate, and 18-crown-6 functional groups, was
      originally developed to overcome this problem. We have found that the addition of
      18-crown-6 to the eluent promotes improved peak resolution between Na+ and NH4+
      even at concentrations as high as 60,000 to 1 using this column. Its use also
      improves the separation of alkali and alkaline earth metal and amine cations.
      Mobile phase 18-crown-6 increased the retention times of CH3NH3+, NH4+, and K+,
      and decreased the retention time of Sr2+. The retention times of Li+, Na+, Mg2+,
      Ca2+, (CH3)2NH2+, and (CH3)3NH+ were not affected. This method makes possible the
      direct analysis of ammonia from nitrogenase, the enzyme responsible for
      biological nitrogen fixation. The resolution of the NH4+ peak from the Na+ and
      Mg2+ peaks improved from zero resolution to values of 6.19 and 5.65,
      respectively. This technique considerably reduces the analysis time of NH4+ in
      the presence of high concentrations of Mg2+ and Na+ over traditional indophenol
      measurements.

PMID- 14601837
TI  - Strategy for developing and optimizing liquid chromatography methods in
      pharmaceutical development using computer-assisted screening and Plackett-Burman
      experimental design.
AB  - We describe a three-step method development/optimization strategy for HPLC
      assay/impurity methods for pharmaceuticals, which include multiple-column/mobile
      phase screening using a system equipped with a column-switching device, further
      optimization of separation by using multiple organic modifiers in the mobile
      phase, and multiple-factor method optimization using Plackett-Burman experimental
      designs. In the first two steps, commercially available chromatography
      optimization software, DryLab, was used to perform computer simulations. This
      allows the method developer to evaluate each condition (one column/mobile phase
      combination) with retention data from two scouting gradient runs. This approach
      significantly reduces the number of runs in method development. After a
      satisfactory separation was obtained, we used a method optimization step with
      Plackett-Burman experimental designs. The purpose of the 16-injection set
      experiments was to evaluate nine method factors with regard to method precision,
      accuracy, sensitivity and specificity. The results provided logical
      justifications in selecting method parameters such as column temperature,
      detection wavelength, injection volume, and sample solvent, etc. In data
      analysis, instead of the traditional mathematical manipulations, we used the
      graphical methods to examine and present data by creating the so-called main
      effect plots. Because replicates of design points were not run, the data did not
      allow the testing of statistical significance. However, it provided visual
      presentations in a way that is easy to understand for the method developer and
      end user alike.

PMID- 14601838
TI  - Business-objective-directed, constraint-based multivariate optimization of high
      performance liquid chromatography operational parameters.
AB  - The goal of a separation can be defined in terms of business needs. One goal
      often used is to provide the required separation in minimum time, but many other
      goals are also possible. These include maximizing resolution within an analysis
      time limit, or minimizing the overall cost. The remaining requirements of the
      separation can be applied as constraints in the optimization of the goal. We will
      present a flexible, business-objective-based approach for optimizing the
      operational parameters of high performance liquid chromatography (HPLC) methods.
      After selecting the stationary phase and the mobile-phase components, several
      isocratic experiments are required to build a retention model. Multivariate
      optimization is performed, within the model, to find the best combination of the
      parameters being varied so that the result satisfies the goal to the fullest
      extent possible within the constraints. Interdependencies of parameters can be
      revealed by plotting the loci of optimal variable values or the function being
      optimized against a constraint. We demonstrate the concepts with a model
      separation originally requiring a 54 min analysis time. Multivariate optimization
      reduces the predicted analysis time to as short as 8 min, depending on the goals
      and constraints specified.

PMID- 14601839
TI  - Determination of isoflavones in red clover and related species by high
      performance liquid chromatography combined with ultraviolet and mass
      spectrometric detection.
AB  - High-performance liquid chromatography-UV-electrospray ionization-mass
      spectrometric detector (HPLC-UV-ESI-MSD) method for determination of isoflavones
      in red clover (Trifolium pratense L.) and related species has been developed. The
      separated isoflavones including aglycones, glycosides and glycoside malonates,
      were individually analyzed and identified by their molecular ions and
      characteristic fragment ion peaks using LC-MSD under MS and MS-MS mode, and in
      comparison with the standard isoflavones. A total of 31 isoflavones were detected
      in red clover. Several isoflavones were also identified for the first time in
      related species, T. repense L. (white clover), T. hybridum L. (alsike clover) and
      T. campestre Schreber (hop trefoil). Based on reversed phase HPLC, all 10
      isoflavone aglycones, daidzein, formononetin, genistein, pseudobaptigenin,
      glycitein, calycosin, prunetin, biochanin A, irilone and pratensein in acidic
      hydrolyzed extracts were successfully separated within 40 min and quantified
      individually by UV and MS detectors. For the 10 target compounds, the
      investigated concentrations ranged from approximately 24 to approximately 12500
      ng/ml for UV detection and approximately 6 to approximately 3125 ng/ml for MS
      detection, and good linearities (r2 > 0.999 for UV and r2 > 0.99 for MS) for
      standard curves were achieved for each isoflavone. The accuracy and repeatability
      (n = 10) were within 15% for these 10 compounds. This is the first method
      reported that enables the simultaneous quantitation of all 10 isoflavone
      aglycones in red clover and related species.

PMID- 14601841
TI  - Speciation of Pt(II) and Pt(IV) in spiked extracts from road dust using on-line
      liquid chromatography-inductively coupled plasma mass spectrometry.
AB  - The emission of platinum from automobile catalytic exhaust converters is well
      known and the accumulation of Pt in road dust has been studied by the analysis of
      total Pt contents. However, there are few studies on the speciation of the
      emitted Pt-compounds in the environment. A separation method with HPLC-UV has
      been developed by Nachtigall et al. [Chromatogr. A 775 (1997) 197] with aqueous
      standards of Pt(II)- and Pt(IV)-chloro complexes. Due to the limited selectivity
      and sensitivity of the UV-detection this method is not suitable for Pt-speciation
      in road dust extracts. Therefore, in this study the method of Nachtigall et al.
      was modified to realize an on-line coupling to ICP-MS with the advantage of Pt
      specific detection. Calibration was performed with aqueous standards and spiked
      road dust extracts. Calibration curves were linear with low residual standard
      deviation (1.3-3.1% for the aqueous standards) and approximately 10-times lower
      detection limits compared to the HPLC-UV-method. Moreover, the stability of the
      model species was investigated using isocratic as well as gradient separation.
      Isotopic ratios of 194Pt, 195Pt, 196Pt and 198Pt were determined for quality
      control. A new mathematical correction method for the HfO-interference on the
      195Pt-signal was developed. Additionally, the elution pattern of further elements
      in the road dust extracts was monitored and total element contents were
      determined in unspiked road dust extracts.

PMID- 14601840
TI  - Aqueous photolysis of the sunscreen agent octyl-dimethyl-p-aminobenzoic acid.
      Formation of disinfection byproducts in chlorinated swimming pool water.
AB  - The photochemical behavior of the sunscreen agent octyl-dimethyl-p-aminobenzoic
      acid (ODPABA) was studied in different aqueous solutions and under different
      conditions. ODPABA photolysis was performed under laboratory conditions using a
      xenon light source and under natural sunlight conditions in sea, swimming pool as
      well as in distilled water. The influence of dissolved organic matter (DOM) on
      the degradation kinetics was also studied in the presence of various
      concentrations of humic acids (HA). The phototransformation was shown to proceed
      via pseudo-first-order reaction in all cases and the reaction rates followed the
      order: distilled water > swimming pool water > seawater, depending mainly on the
      presence of dissolved organic matter that retarded the photolysis reaction.
      Kinetic experiments were monitored with HPLC/UV-DAD and the half-lives (t 1/2)
      varied between 1.6 and 39 h in simulated solar irradiation and between 27 and 39
      h in natural sunlight conditions. The product distribution during illumination
      was strongly dependent on the constitution of the irradiated media. Irradiation
      of the aqueous ODPABA solutions gave rise to several transformation products that
      were isolated by means of solid-phase extraction (SPE) and identified using GC-MS
      techniques. These were formed mainly through dealkylation and hydroxylation
      reactions and were detected in all aqueous solutions investigated. In the case of
      swimming pool water some additional byproducts were isolated and were tentatively
      identified as chlorinated intermediates, formed by the subsequent chlorination of
      the parent molecule as well as other intermediates.

PMID- 14601842
TI  - Predicting gas chromatographic retention times for the 209 polybrominated
      diphenyl ether congeners.
AB  - A gas chromatographic relative retention time (GC-RRT) model was developed to
      predict retention times of the 209 individual polybrominated diphenyl ether
      (PBDE) congeners. Using the available 46 PBDE standards with mono- to deca
      bromination, a multiple linear regression equation of the form RRT = b0 +b1 (no.
      o-Br) + b2(no. m-Br) +b3 (no. p-Br) +b4(mu) +b5 (ln MW) was used to predict the
      RRTs of the remaining 163 PBDE congeners. Molecular descriptors in the model
      included the number of ortho-, meta-, and para-bromine substituents (no. o-Br, m
      Br andp-Br, respectively), the semi-empirically calculated dipole moment (mu),
      and the natural logarithm of molecular weight (MW). A high level of
      predictability (R2 = 0.9972) was obtained for the model.

PMID- 14601843
TI  - Enhanced mass resolution tandem mass spectrometry method for 2,3,7,8
      tetrachlorodibenzo-p-dioxin detection with ion trap mass spectrometry using high
      damping gas pressure.
AB  - Damping gas flow was optimized for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)
      determination using ion trap mass spectrometer. A tandem mass spectrometry (MS
      MS) method with better than unit-mass resolution (mass width, 0.3 u) was
      developed at a damping gas flow of 1.5 ml/min and a collision-induced
      dissociation (CID) voltage of 3.30 V. The relative standard deviation (R.S.D.) at
      the enhanced resolution was 2.9% in 24 h of consecutive injections. The detection
      limit was significantly improved because the efficiency of both precursor ion
      trapping and fragmentation increased with the damping gas flow. Product ion yield
      was 4.5 times higher and limit of detection was 3.2 times lower than at the
      default flow (0.3 ml/min and 1.65 V).

PMID- 14601844
TI  - The cataract scene.

PMID- 14601845
TI  - Sir Nicholas Harold Ridley. He changed the world, so that we might better see it.
AB  - Cataract surgery with intraocular lens (IOL) implantation has become the most
      common and most successful of all operations in medicine. Sir Harold Ridley's
      first cataract extraction with implantation of an IOL marked the beginning of a
      major change in the practice of ophthalmology. Millions of patients worldwide
      have benefited from Sir Ridley's invention, and are likely to continue to derive
      benefit from this device. However, the development of the IOL was not without its
      share of ups and downs. Sir Harold Ridley, the inventor of IOL, died at the age
      of 94, on 25 May 2001, and ophthalmology lost one of its greatest and most
      influential practitioners. We are happy that he lived to enjoy the fruits of his
      labour--to see the amazing improvements and the expansive growth that evolved in
      the cataract-IOL technique, from early and unsatisfactory operations in previous
      decades, to the superb results attainable today. The invention of the IOL has not
      been just the addition of one new form of treatment, but rather, Sir Harold's
      tiny disc-shaped sliver of plastic has changed the world so that our patients may
      better see it. This article presents a brief biographical sketch of Sir Harold
      and lists his major inventions and contributions to ophthalmology.

PMID- 14601846
TI  - Ocular manifestations of Wegener's granulomatosis. Analysis of nine cases.
AB  - PURPOSE: To report a series of nine patients of Wegener's granulomatosis (WG)
      with diverse ocular and systemic manifestations. METHODS: Retrospective analysis
      of nine consecutive patients seen between 1987 and 2002. RESULTS: The mean age at
      the time of diagnosis was 43.89 years (range: 33-56 years). Redness, pain and
      photophobia (8 patients) were the common presenting complaints. Sinusitis (6
      patients) and arthralgia (6 patients) were the commonly associated systemic
      complaints. Necrotising scleritis with peripheral keratopathy (6 patients) was
      the most common ocular sign. Serum antibodies against the cytoplasmic component
      of neutrophils and monocytes (cANCA) were positive in 7 of 8 patients. Biopsy
      diagnosis was done in one patient for whom cANCA was not done. Cyclophosphamide
      and corticosteroids alleviated the symptoms in 6 patients. Ocular and systemic
      condition remained stable in 7 patients. One patient expired due to the severity
      of the disease and another patient was lost to follow-up. CONCLUSIONS: Scleritis
      with peripheral corneal involvement was the most commonly observed ocular
      manifestation of WG in our series. cANCA was a useful adjunct in the diagnosis of
      WG. When clinical and serologic findings were inconclusive, biopsy remained
      indispensable. A combination of cyclophosphamide and corticosteroids is essential
      and critical not only for the ocular condition but also for the survival of the
      patient.

PMID- 14601847
TI  - In-vivo slit scanning confocal microscopy of normal corneas in Indian eyes.
AB  - OBJECTIVE: To study the cellular populations of healthy corneas of Indian eyes
      using confocal microscopy and to evaluate the correlation with age, gender and
      laterality. METHODS: The central corneas of 100 eyes of 50 healthy subjects were
      examined using an in-vivo slit scanning confocal microscope (Confoscan 2). Images
      were analysed for cell densities of the epithelium, stroma and endothelium.
      RESULTS: Good quality images enabling analysis of all cell layer populations were
      obtained in 74 eyes of 43 healthy subjects (22 males and 21 females) with a mean
      age of 31.89 +/- 13.47 (range 19-71 years). The basal epithelial cell density was
      3601.38 +/- 408.19 cells/mm2 (range 3017.3-4231.1 cells/mm2). The mean keratocyte
      nuclei density in the anterior stroma was 1005.02 +/- 396.86 cells/mm2 (range
      571.6-1249.6 cells/mm2) and in the posterior stroma was 654.32 +/- 147.09
      cells/mm2 (range 402.6-1049.1 cells/mm2). Posterior keratocyte nuclei density was
      30.76% less than the anterior stromal keratocyte nuclei density. The difference
      in keratocyte nuclei density was statistically significant (P=0.001). The mean
      endothelial cell density was 2818.1 +/- 361.03 cells/mm2 (range 2118.9-4434
      cells/mm2) and the mean endothelial cell area was found to be 385.44 +/- 42.66
      mm2 (range 268.9-489.2 mm2). Hexagonal cells formed 22.5-69.4% of the endothelial
      cell populations (mean 42.04 +/- 11.81%). Mean coefficient of cell size variation
      was 32.29 +/- 3.06 (range 27.2-39.2). No statistically significant differences
      were found in cell densities of any corneal layer either between female and male
      patients or between right and left eyes. Basal epithelial cell density, anterior
      stromal keratocyte nuclei and posterior stromal keratocyte nuclei density were
      unaffected by age (r=0.12, 0.07, -0.12 respectively) (P=0.001). There was a
      statistically significant negative correlation between mean endothelial cell
      density and increase in age (r=-0.42, P=0.001). Coefficient of cell size
      variation and age were positively correlated (r=0.73, P=0.001). CONCLUSION: In
      vivo slit scanning confocal microscopy is useful for the study of corneal cell
      populations. Our study provides normative data of these cell populations.

PMID- 14601848
TI  - Rhino-orbito-cerebral mucormycosis. A retrospective analysis of clinical features
      and treatment outcomes.
AB  - OBJECTIVE: The conventional management of rhino-orbito-cerebral (ROC)
      mucormycosis includes control of metabolic abnormality, administration of
      amphotericin B and surgery that spans simple sinus clearance, radical debridement
      and orbital exenteration. Recent literature includes anecdotal descriptions of
      successful treatment with conservative management of involved orbits. We
      evaluated the clinical features and outcome of treatment for the different stages
      of ROC mucormycosis. METHOD: In this retrospective case series, 34 case records
      of patients with a histopathological diagnosis of ROC mucormycosis treated
      between 1992 and 2000 were reviewed. Three clinical stages and three treatment
      groups were identified. Patients with limited sino-nasal disease (Clinical stage
      I) underwent sino-nasal debridement (Treatment group A). Patients with limited
      rhino-orbital disease (Clinical stage II) underwent either sino-nasal debridement
      alone (Treatment group A) or orbital exenteration in addition to sino-nasal
      debridement (Treatment group B). Patients with rhino-orbito-cerebral disease
      (Clinical stage III) did not undergo any surgical procedure (Treatment group C).
      Thirty-three patients received intravenous amphotericin B. Outcome for each group
      was measured as "Treatment success" (disease free, stable patient with metabolic
      abnormality under control) and "Treatment failure" (progression of disease with
      worsening general condition or mortality due to the disease). RESULTS:
      Uncontrolled diabetes in 30 (88.2%) of 34 patients was the commonest underlying
      disease and 16 (53.3%) of 30 diabetics had ketoacidosis. Chronic renal failure (n
      = 4), hepatic disease (n = 3) and idiopathic thrombocytopenia (n = 1) were the
      other underlying diseases. Eleven patients had stage I disease, 16 patients had
      stage II disease and seven patients had stage III disease. All 11 patients with
      stage I disease received treatment A; of 16 patients with stage II disease, 7
      received treatment A and the remaining with stage III disease received treatment
      B; 7 patients with stage II disease received treatment C. Ten of 11 patients
      (91%) with stage I disease had treatment success. In patients with stage II
      disease, 7 of 7 (100%) with treatment A and 1 of 9 (11.1%) with treatment B had
      treatment success. All seven patients with stage III disease had treatment
      failure. CONCLUSION: Debridement of the sinuses is necessary in all cases of
      rhino-orbito-cerebral mucormycosis. Diagnosis in the early stage needs a high
      degree of suspicion. There is a definite role for retention of orbits in patients
      whose metabolic derangement is rapidly controlled and orbital involvement is non
      progressive.

PMID- 14601849
TI  - Intraocular irrigating solutions. A clinical study of BSS Plus and dextrose
      bicarbonate fortified BSS as an infusate during pars plana vitrectomy.
AB  - PURPOSE: To compare the effect of Balanced Salt Solution Plus (BSS Plus, Alcon
      Laboratories, Fort Worth, Texas, USA) and fortified regular BSS on the cornea and
      lens, when used for continuous irrigation in pars plana vitrectomy (PPV) surgery.
      METHODS: Prospective, investigator masked, randomised study. Forty patients were
      randomly assigned to undergo PPV using BSS Plus (n=20) or fortified BSS (n=20)
      [regular BSS, fortified with 10.5 cc. of dextrose in water (D5W) and 13.1 cc. of
      8.4% sodium bicarbonate]. Intraoperative features of the corneal epithelium,
      postoperative changes in the corneal endothelial cell denstiy (ECD) at 3 months,
      and clarity of the lens during surgery and postoperatively were evaluated.
      RESULTS: Intraoperative epithelial changes were similar in both groups with 7
      (35%) of the cases having the epithelium removed in the BSS Plus group and 8
      (40%) in the BSS fortified group (P=0.23). The mean differences in ECD (3 months
      versus preoperative) in the operated eyes when adjusted for changes in the
      control eye showed no difference with the type of BSS (P=0.98). Intraoperative
      lens changes were more significant (P=0.018) in the BSS fortified group.
      Postoperative lens status at 3 months was similar for both groups. Though there
      was a trend towards worse postoperative nuclear sclerosis change in the BSS
      fortified group, it was not significant (P=0.160). CONCLUSION: Standard BSS
      fortified with dextrose and bicarbonate is an efficacious infusion fluid during
      pars plana vitrectomy. Both solutions showed comparable effects on postoperative
      corneal endothelial cell density and corneal epithelial changes intraoperatively.
      BSS fortified has more lenticular changes intraoperatively than BSS Plus although
      no lens had to be removed in either group. The study implications are important
      since BSS fortified is significantly less expensive than BSS Plus.

PMID- 14601850
TI  - Transpupillary thermotherapy for treatment of choroidal neovascularization
      secondary to age-related macular degeneration in Indian eyes.
AB  - AIM: To evaluate the efficacy of transpupillary thermotherapy (TTT) for treatment
      of subfoveal choroidal neovascularisation (CNV) secondary to age-related macular
      degeneration (AMD), and to define accurate power settings for this procedure in
      Indian eyes. METHODS: A prospective, nonrandomised study of 160 eyes of 144
      patients with subfoveal CNV. The laser settings included 2 mm spot and 300 mw
      power or 3 mm spot and 400-600 mw power. Two separate 3 mm spots were used in
      larger lesions. The treatment was given for 60 seconds at each point. RESULTS:
      Ninety-nine eyes had classic membranes and 61 eyes had occult membranes.
      Following treatment, 79 of 99 (79.8%) classic and 52 of 61 (85%) occult membranes
      regressed. Visual improvement (> or = 2 lines) was seen in 29 (29.3%) eyes and 12
      (19.6%) eyes; visual stabilisation (1 line) in 39 (39.4%) eyes, and 35 (57.4%)
      eyes; and reduction of vision (< or = 2 lines) in 31 (31.3%) eyes and 14 (22.9%)
      eyes with classic and occult membranes respectively. Mean follow-up was 12
      months. One patient suffered inadvertant foveal burn. CONCLUSION: TTT is
      effective in the management of subfoveal membranes in Indian eyes. They respond
      to lower energy levels compared to the Caucasian eyes.

PMID- 14601851
TI  - Does internal limiting membrane peeling in macular hole surgery improve reading
      vision?
AB  - PURPOSE: To document the effect of internal limiting membrane (ILM) peeling in
      macular hole closure and reading vision. METHOD: Fifty-four patients with
      idiopathic and traumatic macular hole underwent standard vitreous surgery and
      received either ILM peeling (n=25) or no ILM peeling (n=29). The hole closure,
      and Snellen acuity (distant and near) were recorded 12 weeks after surgery and
      statistically analysed. RESULTS: The macular hole closure rate was 96% (24 of 25)
      and 72.4% (21 of 29) with and without ILM peeling respectively (P = 0.028).
      Distant vision improvement of two or more lines was recorded in 64% (16 of 25)
      and 51.7% (15 of 29) eyes (P = 0.417) with and without ILM peeling respectively.
      Near vision improvement of two or more lines was seen in 68% (17 of 25) and 41.2%
      (12 of 29) eyes (P = 0.048) with and without ILM peeling respectively.
      CONCLUSION: ILM peeling in macular hole surgery improves the macular hole closure
      rate and reading vision.

PMID- 14601852
TI  - Prolapsed intraocular aspergilloma masquerading as malignant melanoma.
AB  - We describe an aspergilloma that masqueraded as an intraocular malignant melanoma
      in an elderly male patient.